PMID- 11440783
TI  - Folate levels and N(5),N(10)-methylenetetrahydrofolate reductase genotype (MTHFR)
      in mothers of offspring with neural tube defects: a case-control study.
AB  - BACKGROUND: Neural tube defects (NTDs) have been associated with biochemical
      factors involved in the conversion of homocysteine to methionine as folate
      deficiency and the mutation 677T in the N(5),N(10)-methylenetetrahydrofolate
      reductase gene (MTHFR). METHODS: A case-control study was performed to detect
      this mutation in 38 unrelated women with NTD deceased products and 31 mothers
      without antecedents of NTD offspring. All products were born in Nuevo Leon
      (northeastern Mexico) during 1997. Erythrocyte and plasmatic folate levels and
      the genotype of the 677 polymorphism at the MTHFR locus were analyzed in both
      groups. RESULTS: Although no significant differences were found in mean blood
      folate levels, the percentage of women in the case group with erythrocyte folate
      levels <160 ng/mL was significantly higher than in the control group (75 vs.
      51.2%, p <0.05). The proportion of women with plasma folate levels <3.5 ng/mL was
      higher in the case group (16.2 vs. 0%, p <0.01). Genotype analysis demonstrated a
      significantly higher proportion of 677T homozygous mothers with NTD products
      (39.6 vs. 9.1%, p <0.05). Allele frequencies for the 677T mutation were 0.55 and
      0.36 for cases and controls, respectively. The odds ratio (OR) for having a NTD
      product was 6.1 (95%, CI 1.56-23.6) for homozygous 677T mothers vs. homozygous
      677C and heterozygous mothers. Significantly low levels of erythrocyte folate
      were found in the 677C homozygous case group and in plasma folate in the
      677C/677T heterozygous case mothers. CONCLUSIONS: Our study suggests that folate
      deficiency and MTHFR unfavorable genotype in mothers are important risk factors
      for severe NTD phenotype in our population.

PMID- 11440784
TI  - Catalase/superoxide dismutase (SOD) and catalase/paraoxonase (PON) ratios may
      implicate poor glycemic control.
AB  - BACKGROUND: Previous studies suggest that elevated oxidative stress implicates
      poor glycemic control resulting in the development of diabetic complications. By
      evaluating the relationship between paraoxonase (PON) and antioxidant enzyme
      activities and glycemic control in diabetic patients with and without
      complications, we investigated whether there is a role of PON and/or antioxidant
      status in glycemic control. METHODS: A total of 107 patients with type 2 diabetes
      mellitus (DM) was included in the study. Seventy-five patients had complications
      including microangiopathy, proliferative retinopathy, and/or nephropathy while 32
      had no complications. The control group consisted of 29 age- and sex-matched
      healthy persons. Serum superoxide dismutase (SOD) and catalase activities were
      measured according to Sun and Goth, respectively. Basal and salt-stimulated
      paraoxonase activities and arylesterase activity were determined using the method
      of Eckerson et al. RESULTS: There was an increase in the catalase activity and a
      decrease in the basal and salt-stimulated PON activity of patients when compared
      with controls, while no significant difference was observed in SOD activity. PON
      phenotypes had no effect on any parameter in patient and control groups. The
      ratio of catalase/SOD was 2.44 +/- 7.10 and 0.17 +/- 0.09 in diabetics and
      controls, respectively (p = 0.004); this was associated with an elevation in
      HbA1c levels. On the other hand, catalase/PON ratio was also enhanced in diabetic
      patients (2.8 +/- 5.2), showing a relationship with HbA1c levels compared to
      controls (0.29 +/- 0.3, p = 0.000). CONCLUSIONS: The data of this study reveal
      that enhanced catalase/SOD and catalase /PON ratios that are correlated with
      HbA1c levels are observed in diabetic patients; thus, these ratios may be used as
      markers of poor glycemic control and as risk factors in the development of
      diabetic complications.

PMID- 11440785
TI  - Increments in whole body bone mineral content associated with weight and length
      in pre-term and full-term infants during the first 6 months of life.
AB  - BACKGROUND: The objective of the present study was to assess bone mineral content
      (BMC) of the whole skeleton in pre-term and full-term healthy infants and the
      factors influencing BMC, such as bone area, birth weight, birth length, current
      weight, current length, gender, and gestational age. METHODS: Forty-eight healthy
      full-term infants and 34 healthy premature infants fed predominantly with intact
      human milk were studied. BMC was measured monthly with dual energy X-ray
      absorptiometry (DEXA). At the same time, length and weight were measured and
      registered. Pre-term infants were studied at 60-day intervals. RESULTS: For both
      full-term and pre-term infants, BMC increased during the first months of life.
      However, the values of pre-term infants never reached the values of full-term
      infants, even after correcting for age and weight. For both full-term and pre
      term infants, BMC was significantly correlated at the second month with birth
      weight (r = 0.901), birth length (r = 0.860), gestational age (r = 0.803), bone
      area (r = 0.960), current weight (r = 0.920), and current length (r = 0.840, p
      <0.001 for all correlation coefficients). Multivariate analysis revealed that
      bone area was the most important factor in predicting BMC. CONCLUSIONS: Pre-term
      children have lower BMC than full-term children. The main factor explaining this
      apparent osteopenia is bone area. Pre-term children have a higher daily
      mineralization rate than full-term children, but this catch-up mineralization is
      not enough to reach BMC levels seen in full-term children.

PMID- 11440786
TI  - Heterozygous beta-thalassemia: not infrequent in Mexico.
AB  - BACKGROUND: The prevalence of beta-thalassemia in Mexico is not known in detail.
      METHODS: Data of studies investigating abnormal hemoglobins between September
      1987 and November 2000 were analyzed; in addition, data of red-blood-cell indices
      and clinical features were analyzed in patients identified as carriers of beta
      thalassemia. RESULTS: In 1,639 prospective studies looking for abnormal
      hemoglobins, 429 disclosed some abnormality; of these, 319 cases displayed
      abnormally high levels of hemoglobin A2, thus consistent with the diagnosis of
      beta-thalassemia. This hemoglobin abnormality represented 74.2% of all
      abnormalities, both quantitative and qualitative, of the molecule of hemoglobin.
      There were 317 heterozygotes and only two homozygotes. We have previously shown
      that the most frequent cause of anemia as the iatrotropic condition in Mexican
      mestizos is iron deficiency. We found that iron deficiency is 11.5 times more
      frequent than beta-thalassemia and that the latter is 1.3 times more frequent
      than macrocytic/megaloblastic anemia. CONCLUSIONS: beta-thalassemia should not be
      considered as infrequent in Mexico, and individuals with red blood cell
      microcytosis and/or hypochromia with or without anemia should be screened for
      thalassemia.

PMID- 11440787
TI  - Clinical impact of histidine-ketoglutarate-tryptophan (HTK) cardioplegic solution
      on the perioperative period in open heart surgery patients.
AB  - BACKGROUND: Ischemia-reperfusion injury during open heart surgery related to
      unsuccessful myocardial protection may increase morbidity or mortality. We
      analyze the clinical outcome after cardiac surgery with a cardioplegic solution
      based on intracellular components added with histidine-ketoglutarate-tryptophan.
      METHODS: Thirty patients programmed for elective open heart surgery were
      randomized into two groups. In group I (n = 15), myocardial protection was
      carried out with Bretschenider solution (HTK), and in group II (n = 15) with
      conventional crystalloid cardioplegia. The incidence of arrhythmias, inotropic
      support requirement, and length-of-stay in the intensive care unit were
      evaluated. RESULTS: During reperfusion, there was no difference in incidence of
      arrhythmias; however, in the postoperative period group I had a lower incidence
      of arrhythmias (p = 0.001). Inotropic support (p = 0.003) and length-of-stay in
      the intensive care unit (p = 0.037) were lower in group I. There were no deaths
      in either group. CONCLUSIONS: It was concluded that myocardial protection with
      Bretschneider solution effectively decreases incidence of arrhythmias, inotropic
      support, and length-of-stay in the intensive care unit.

PMID- 11440788
TI  - Low serum magnesium levels and foot ulcers in subjects with type 2 diabetes.
AB  - BACKGROUND: Hypomagnesemia is associated with the development of neuropathy and
      abnormal platelet activity, both of which are risk factors for the progression of
      ulcers of the feet. Thus, the aim of this study was to determine the relationship
      between low serum magnesium and foot ulcer in subjects with type 2 diabetes.
      METHODS: Thirty-three out-patients with type 2 diabetes and foot ulcers (16 women
      and 17 men) were compared with a control group of 66 out-patients with type 2
      diabetes without foot ulcers (35 women and 31 men), matched by age, diabetes
      duration, HbA1c, and glycemia. Patients with foot ulcers were included in the
      study only if a foot ulceration onset not exceeding 2 months was established.
      Patients diagnosed with reduced renal function, a history of alcohol intake, or
      as having received magnesium supplementation or diuretics were not included.
      Serum magnesium was measured by colorimetric method. The relationship between
      serum magnesium and foot ulcers was assessed by logistic regression. RESULTS:
      Hypomagnesemia was identified in 31 (93.9%) subjects with foot ulcers, and 49
      (73.1%) control subjects, p = 0.02. Subjects with foot ulceration had lower serum
      magnesium levels (1.48 +/- 0.33) than those in the control group (1.68 +/- 0.32),
      p <0.001. Logistic regression analysis showed a significant relationship between
      low serum magnesium levels and foot ulcers (odds ratio [OR] 2.9, CI 95% 1.7-6.8;
      p = 0.01). CONCLUSIONS: Serum magnesium depletion is present and shows a strong
      relationship with foot ulcers in subjects with type 2 diabetes and foot ulcers, a
      relationship not previously reported.

PMID- 11440789
TI  - Risk factors for intrahospital infection in newborns.
AB  - BACKGROUND: Intrahospital infection (IHI) in the newborn (NB) is a morbidity
      problem that increases mortality rates in this age group because the infecting
      microorganism is more aggressive. The objective of this study was to compare risk
      factors for localized or systemic IHIs between groups of NBs with and without
      IHIs. METHODS: This was a retrospective study of two groups of patient records
      from January 1995 to December 1998. Group A (cases) was made up of 73 patients
      with documented IHIs and Group B (controls), 105 patients without IHIs.
      Descriptive and inferential statistics (Student t, Mann-Whitney U, Wilcoxon rank
      sum, Chi square, and Fisher exact tests) were used. Odds ratio (OR) and multiple
      logistic regression were used to study risk factors. Statistical significance was
      considered at p <0.05. RESULTS: Average gestational age was 35.4 +/- 4.3 weeks in
      Group A patients and 37.4 +/- 3.2 weeks for Group B patients with p = 0.001. Risk
      factors studied by means of OR (low birth weight, prematurity of 30 weeks of
      gestational age or less, prolonged intrahospital stay, etc.) showed statistical
      significance. Also showing significance were other not-well-studied factors such
      as higher numbers of diagnoses and blood transfusions. After multivariate
      analysis, the group of risk factors more associated with IHIs included vein
      dissection for insertion of central venous catheter, orotracheal intubation, and
      prolonged intrahospital stay (12 days or more) with an accumulative r of 0.6112.
      CONCLUSIONS: We conclude that there are several known risk factors for IHIs and
      others not well described to date that must be avoided to the extent possible in
      the NB, particularly in the premature newborn population.

PMID- 11440790
TI  - Epidemiologic panorama of stomach cancer mortality in Mexico.
AB  - BACKGROUND: Annually, there are more than 6 million deaths from a type of
      malignant neoplasia worldwide. In developing countries, the highest rates of
      incidence of malignant neoplasias are uterine cervical cancer, stomach, lung,
      esophagus, pharynx, and liver cancers. Recent estimates on the incidence of
      cancer worldwide show that, in 1990, stomach cancer (SC) was the second most
      frequent type of cancer (900,000 new cases annually). Rates of incidence have
      decreased consistently in nearly all areas of the world. In Mexico, however,
      rates of incidence and mortality have increased gradually between 1980 and 1997;
      in 1995, 4,685 people died of SC in Mexico. This report presents a descriptive
      analysis of SC mortality in Mexico. METHODS: A mortality database edited from the
      electronic files of the National Institute of Informatics, Statistics and
      Geography (INEGI) in Mexico was used; population denominators were edited by the
      Mexican National Population Council (Conapo). Adjusted mortality rates, taking as
      standard of reference the population of Mexico City by sex, year, and 10-year age
      groups were calculated as well as the sex ratio for the 1980-1997 period. To
      evaluate the magnitude of risks by state, the standardized mortality ratio (SMR)
      was calculated; prematurity was evaluated through the potential lost-life years
      index (PLLYI). The analysis was carried out using the Excel and Stata 5.0
      software programs. RESULTS: During the years from 1980 to 1997, in Mexico the
      total number of deaths from SC was 76,315. The male:female ratio was 1.2:1.0. SMR
      by state showed that the states of Yucatan, Sonora, Zacatecas, Michoacan, and
      Chiapas had higher mortality rates. The PLLYI was higher for males in the states
      of Chiapas, Sonora, Chihuahua, Zacatecas, and Southern Baja California, and
      higher for females in Chiapas, Oaxaca, Yucatan, Puebla, and Campeche.
      CONCLUSIONS: World statistics on mortality caused by SC suggest a decreasing
      trend. Findings for this study show an increase in the adjusted mortality rates
      by SC during the 1980-1997 period in Mexico. However, when analyzing the
      different indicators that reveal risks, magnitude, and prematurity of mortality,
      there is a differential trend in mortality by sex that includes regional patterns
      probably related to different socioeconomic levels.

PMID- 11440791
TI  - Shwachman-Diamond syndrome in a Mexican family.
AB  - Shwachman-Diamond Syndrome (SDS) is an inherited condition with multisystemic
      abnormalities including pancreatic exocrine dysfunction, neutropenia, short
      stature, and skeletal abnormalities. In this report, we describe the case of a 14
      year-old female with a history of neutropenia, pancreatic exocrine insufficiency
      and pancreatic endocrine sufficiency, pancreatic lipomatosis (10), and the
      development of myeloid leukemia. Postmortem examination revealed a high
      probability of SDS. We also describe the clinical findings in the patient's six
      siblings, suggesting this as a familial form of SDS. Because the gene(s)
      responsible for this syndrome have not yet been identified, genetic confirmation
      is not yet possible. This is the first report in the literature of a Mexican
      family with probable SDS.

PMID- 11440793
TI  - Fibrillar beta-amyloid evokes oxidative damage in a transgenic mouse model of
      Alzheimer's disease.
AB  - Beta-amyloid is one of the most significant features of Alzheimer's disease, and
      has been considered to play a pivotal role in neurodegeneration through an
      unknown mechanism. However, it has been noted that beta-amyloid accumulation is
      associated with markers of oxidative stress including protein oxidation (Smith et
      al., 1997), lipid peroxidation (Mark et al., 1997; Sayre et al., 1997), advanced
      glycation end products (Smith et al., 1994), and oxidation of nucleic acids
      (Nunomura et al., 1999). Furthermore, studies from cultured cells have shown that
      beta-amyloid leads to an increase in hydrogen peroxide levels (Behl et al.,
      1994), and the production of reactive oxygen intermediates (Harris et al., 1995).
      Taken together, this evidence supports the idea that beta-amyloid plays a key
      role in oxidative stress-evoked neuropathology. In this study, we examined the
      induction of oxidative stress in response to amyloid load in a mouse model of
      Alzheimer's disease. The mice carrying mutant amyloid precursor protein and
      presenilins-1 (Goate et al., 1991; Hardy, 1997), develops beta-amyloid deposits
      at 10-12 weeks of age and show several features of the human disease (Holcomb et
      al., 1998; Matsuoka et al., 2001; McGowan et al., 1999; Takeuchi et al., 2000;
      Wong et al., 1999). Both 3-nitrotyrosine and 4-hydroxy-2-nonenal (protein and
      lipid oxidative stress markers, respectively) associate strongly with fibrillar
      beta-amyloid, but not with diffuse (thioflavine S negative) beta-amyloid, and the
      levels increase in relation to the age-associated increase in fibrillar amyloid
      load.From these data we suggest that fibrillar beta-amyloid is associated with
      oxidative damage which may influence disease progression in the Alzheimer's
      disease brain.

PMID- 11440794
TI  - A novel, associative process modulating photic resetting of the circadian clock.
AB  - Appropriate timing of physiological and behavioral processes requires that the
      circadian clock be reset daily by salient cues in the environment, particularly
      light. It is known that the ability of light to reset the clock depends both on
      its intensity and on the circadian time when it is applied (Daan and Pittendrigh,
      1976; Moore-Ede et al., 1982). Here we show that the ability of a weak light
      stimulus to reset the clock is dramatically enhanced when it is presented daily
      at the same circadian time. Equivalent daily presentations of this light
      stimulus, but at different circadian times each day, do not lead to such
      enhancement. These findings suggest that the ability of light to reset the clock
      can be modified through a novel, and previously unrecognized, conditioning-like
      associative process in which circadian time serves as the conditioned stimulus
      and light as the unconditioned stimulus. The idea that circadian time can serve
      as a conditioned stimulus to modulate the effectiveness of light provides a new
      perspective on the lasting impact that light schedules have on the circadian
      clock and, thus, may have implications for existing models of photic entrainment
      (Pittendrigh and Daan, 1976; Moore-Ede et al., 1982).

PMID- 11440795
TI  - Theta-rhythmically firing neurons in the anterior thalamus: implications for
      mnemonic functions of Papez's circuit.
AB  - In 1937 Papez described an anatomical circuit (or loop) beginning and ending in
      the hippocampal formation that he proposed subserved emotional experience (Papez,
      1937). Specifically, the projections of the circuit were as follows: hippocampal
      formation--> mammillary bodies--> anterior thalamus--> cingulate cortex-->
      parahippocampal gyrus--> hippocampal formation. Although the circuit has been
      refined based on subsequent anatomical findings (Amaral and Witter, 1995;
      Shibata, 1992; Van Groen and Wyss, 1995), the major links of the circuit
      unquestionably represent a prominent system of connections in the mammalian
      brain. Hence, the enduring nature of 'Papez's circuit'. Unlike, however, its
      persistence as anatomical entity, the proposed functional role for the circuit
      has been less resilient. The early notion that Papez's circuit subserves
      emotional experience/expression has been abandoned (LeDoux, 1993) and replaced by
      the proposal that it is primarily involved in mnemonic functions (Aggleton and
      Brown, 1999). Lesions of each of the major components of the circuit have been
      shown to disrupt memory (Aggleton and Brown, 1999; Sutherland et al., 1988;
      Sziklas and Petrides, 1993). The mammillary bodies represent a major output from
      the hippocampus in Papez's circuit (Amaral and Witter, 1995). It has recently
      been shown that cells of mammillary body fire rhythmically in bursts synchronous
      with the theta rhythm of the hippocampus (Bland et al., 1995; Kirk et al., 1996;
      Kocsis and Vertes, 1994, 1997) and that this rhythmical activity is dependent
      upon the action of the hippocampus on the mammillary bodies (Bland et al., 1995;
      Kirk et al., 1996). It is well established that the mammillary bodies project
      massively to the anterior thalamus (Shibata, 1992), which taken together with the
      demonstration that mammillary body cells fire synchronously with theta, suggests
      that the mammillary bodies may act on the anterior thalamus, possibly in the
      manner that the hippocampus acts on the mammillary bodies, to rhythmically
      activate cells of the anterior thalamus at theta frequency. We demonstrated that
      approximately 75% of cells of the anterior ventral nucleus of the thalamus fire
      rhythmically synchronous with the hippocampal theta rhythm and the activity of
      46% of these anterior ventral neurons was highly correlated with theta. These
      findings, together with demonstration of theta-rhythmically firing cells in other
      structures of Papez's circuit, indicate that a theta-rhythmic signal may resonate
      throughout Papez's circuit, possibly involved in the control of mnemonic
      functions of the circuit.

PMID- 11440796
TI  - Opposite genotype-dependent mesocorticolimbic dopamine response to stress.
AB  - Identification of relevant phenotypes related to neural functioning has yet to
      receive the needed attention, although behavioral phenotyping, through
      comparative studies in inbred strains of mice, has produced some major findings
      (Cabib et al., 2000; Crabbe, 1999; Gerlai, 1996; Lathe, 1996). Central responses
      to stress play a major psychopathogenic role in the presence of a genetic
      liability (Fowels, 1992), and mesocortical and mesoacumbens dopamine metabolism
      and release are the most relevant among these responses (Abercrombie et al.,
      1989; Cabib and Puglisi-Allegra, 1994; Chrapusta et al., 1997; Di Chiara et al.,
      1999; Herve et al., 1979; Imperato et al., 1991). Therefore, in the present
      study, we assessed strain-dependent differences in mesocortical and mesoaccumbens
      dopamine responses to a widely utilized stressful procedure (restraint), by
      comparing mice of the oldest and most studied inbred strains (Cabib et al.,
      2000): the C57BL/6JIco and DBA/2JIco. We found that stress produced inhibition of
      mesoaccumbens dopamine release accompanied by a very fast and strong activation
      of mesocortical dopamine metabolism in C57BL/6JIco mice, and the opposite in mice
      of the DBA/2JIco strain. These results suggest a genetic control over the balance
      between mesocortical and mesoaccumbens dopamine responses to stress, and provide
      a model for pre-clinical studies on molecular genetics of depression.

PMID- 11440797
TI  - Independent patterns of transcription for the products of the rat cholinergic
      gene locus.
AB  - The cholinergic phenotype requires the expression of the vesicular acetylcholine
      transporter and choline acetyltransferase proteins. Both genes are encoded at one
      chromosomal location called the cholinergic gene locus. We have identified by in
      situ hybridization histochemistry distinct patterns of transcription from the
      cholinergic gene locus in the subdivisions of the rat cholinergic nervous system.
      The vesicular acetylcholine transporter and choline acetyltransferase are co
      expressed in cholinergic neurons at all developmental stages in all major types
      of cholinergic neurons. The relative levels of vesicular acetylcholine
      transporter and choline acetyltransferase transcripts, however, change
      substantially during development in the CNS. They also differ dramatically in
      distinct subdivisions of the mature cholinergic nervous system, with vesicular
      acetylcholine transporter mRNA expressed at high levels relative to choline
      acetyltransferase mRNA in the peripheral nervous system, but at equivalent levels
      in the CNS. Expression of the R-exon, the presumptive first non-coding exon
      common to both the vesicular acetylcholine transporter and choline
      acetyltransferase, was not detectable at any developmental stage in any of the
      cholinergic neuronal subtypes in the rat nervous system. Thus, in contrast to
      less complex metazoan organisms, production of the vesicular acetylcholine
      transporter and choline acetyltransferase via a common differentially spliced
      transcript does not seem to occur to a significant extent in the rat. We suggest
      that separate transcriptional start sites within the cholinergic gene locus
      control vesicular acetylcholine transporter and choline acetyltransferase
      transcription, while additional elements are responsible for the specific
      transcriptional control of the entire locus in cholinergic versus non-cholinergic
      neurons. Independent transcription of the vesicular acetylcholine transporter and
      choline acetyltransferase genes provides a mechanism for regulating the relative
      expression of these two proteins to fine-tune acetylcholine quantal size in
      different types of cholinergic neurons, both centrally and peripherally.

PMID- 11440798
TI  - Detection of corticotropin-releasing hormone receptor 1 immunoreactivity in
      cholinergic, dopaminergic and noradrenergic neurons of the murine basal forebrain
      and brainstem nuclei--potential implication for arousal and attention.
AB  - Corticotropin-releasing hormone (CRH) interacts with noradrenergic, dopaminergic
      and cholinergic systems of the brain, and these interactions are thought to be of
      relevance for the stress response, anxiety-related behavior, and cognitive
      function. CRH mediates its central effects through two high-affinity membrane
      receptors, CRH receptor subtypes 1 and 2. It is however unclear at present
      whether cholinergic or catecholaminergic cells express these receptors themselves
      or whether the effects of CRH are indirectly mediated through interaction with
      other neurotransmitter systems. Therefore, this study investigated whether
      choline acetyltransferase immunoreactive neurons of the murine basal forebrain
      and brainstem nuclei, and tyrosine hydroxylase immunoreactive neurons located
      within the locus coeruleus, ventral tegmental area and substantia nigra co
      express CRH receptor 1, employing a double-immunocytochemical procedure. Using an
      antibody against the C-terminus of the CRH type 1 receptor (CRH-R1), CRH-R1-like
      immunoreactivity was found in all cholinergic basal forebrain nuclei except the
      nucleus basalis magnocellularis. In particular, the diagonal band of Broca
      (vertical and horizontal limbs) showed a high degree of co-localization of CRH-R1
      immunoreactivity and choline acetyltransferase immunoreactivity (both limbs
      >90%). A less intense immunoreactivity but still high rate of co-localization was
      detected in the cholinergic neurons of the medial septum (80%), while lowest co
      localization was observed in choline acetyltransferase immunoreactive neurons of
      the substantia innominata (58%). An intermediate degree of co-localization (75%)
      was seen in the brainstem pedunculopontine tegmental nucleus, while the other
      major brainstem cholinergic nucleus, the laterodorsal tegmental nucleus, showed
      an even higher degree of choline acetyltransferase immunoreactivity-positive
      cells also immunoreactive for CRH-R1 (92%). All catecholaminergic structures
      studied displayed a pattern of CRH-R1 immunoreactivity strongly overlapping the
      pattern of tyrosine hydroxylase immunoreactivity. The intensity of the CRH-R1
      signal was relatively low within the ventral tegmental area and the substantia
      nigra pars compacta, while the CRH-R1 signal was very intense and detected in
      almost all of the neurons of the locus coeruleus. These results clearly
      demonstrate that the cholinergic and catecholaminergic systems provide direct
      anatomical substrates for CRH action through the CRH-R1. These findings are of
      particular relevance for understanding the action of recently developed CRH-R1
      antagonistic drugs which may offer a new therapeutic approach to treat stress
      related disorders such as anxiety and depression and their concomitant
      alterations in arousal and cognitive functions.

PMID- 11440799
TI  - Amyloid precursor protein associates independently and collaboratively with PTB
      and PDZ domains of mint on vesicles and at cell membrane.
AB  - The mint family consists of evolutionarily conserved adapter proteins from
      Caenorhabditis elegans to mammalian neurons. Three mammalian isoforms, mint1, 2,
      and 3, are extensively diverted in their N-terminal halves and, in striking
      contrast, are highly homologous to each other in their C-terminal halves
      containing phosphotyrosine-binding (PTB) and PSD-95/DLG-A/ZO-1 (PDZ) domains that
      work as protein-protein interaction modules. Biochemical and genetic analyses
      revealed that mint1 and LIN-10, a homolog in C. elegans, comprise macromolecular
      complexes in the presynaptic and postsynaptic terminals, thereby bringing
      synaptic vesicles to the exocytotic transmitter release site and localizing
      receptors and ion channels in the specific membrane domains. Amyloid precursor
      protein is one of the targets of the PTB domain of mint and this interaction
      modulates its proteolytic procedures ending up with amyloid beta peptide
      production, but its molecular mechanism is unclear. We show by an in situ
      hybridization technique that mint3, a ubiquitous isoform, is expressed both in
      polar cells like neurons, and in non-polar cells, such as glia and ependymal
      cells, in the mouse brain. In addition, a considerable amount of a human homolog
      mint3 (approximately 70 kDa) was expressed in a human epithelial cell line.
      Subcellularly, mint3 is specifically enriched in vesicles in the cytoplasm, cell
      membrane, and Golgi complex as reserves. A series of deletions or site-directed
      mutations revealed that mint3 double recognizes an amyloid precursor protein
      containing macromolecular complex via the PTB and PDZb domains independently and
      cooperatively, not only in the cytoplasmic transporting vesicles but even after
      amyloid precursor protein was targeted and/or inserted to the specific cell
      membrane domains. From these results we suggest that mint3 links amyloid
      precursor protein to other components, thereby regulating its transport,
      endocytosis, and metabolism. Abnormal metabolism of amyloid precursor protein
      causes an early-onset type of Alzheimer's disease but its molecular mechanism is
      incompletely understood. The present findings give morphological evidence and a
      molecular framework of how mint interacts with amyloid precursor protein and
      modifies its processing on the secretory pathway.

PMID- 11440800
TI  - Remembering familiar people: the posterior cingulate cortex and autobiographical
      memory retrieval.
AB  - Most functional imaging studies of memory retrieval investigate memory for
      standardized laboratory stimuli. However, naturally acquired autobiographical
      memories differ from memories of standardized stimuli in important ways.
      Neuroimaging studies of natural memories may reveal distinctive patterns of brain
      activation and may have particular value in assessing clinical disorders of
      memory. This study used functional magnetic resonance imaging to investigate
      brain activation during successful retrieval of autobiographical memories
      elicited by name-cued recall of family members and friends. The caudal part of
      the left posterior cingulate cortex was the most strongly activated region and
      was significantly activated in all eight subjects studied. Most subjects also
      showed significant activation of the left anterior orbitomedial, anterior middle
      frontal, precuneus, cuneus, and posterior inferior parietal cortices, and the
      right posterior cingulate and motor cortices.Our findings are consistent with
      prior studies showing posterior cingulate cortex activation during
      autobiographical memory retrieval. This region is also consistently activated
      during retrieval of standardized memory stimuli when experimental designs
      emphasizing successful retrieval are employed. Our results support the hypothesis
      that the posterior cingulate cortex plays an important role in successful memory
      retrieval. The posterior cingulate cortex has strong reciprocal connections with
      entorhinal and parahippocampal cortices. Studies of early Alzheimer's disease,
      temporal lobectomy, and hypoxic amnesia show that hypometabolism of the posterior
      cingulate cortex is an early and prominent indicator of pathology in these
      patients. Our findings suggest that autobiographical memory retrieval tasks could
      be used to probe the functional status of the posterior cingulate cortex in
      patients with early Alzheimer's disease or at risk for that condition.

PMID- 11440801
TI  - Growth hormone as a neuronal rescue factor during recovery from CNS injury.
AB  - There is growing evidence to suggest that growth hormone plays a role in the
      growth and development of the CNS. Specifically, growth hormone has been
      implicated in promoting brain growth, myelination, neuronal arborisation, glial
      differentiation and cognitive function. Here we investigate if growth hormone has
      a role in the recovery from an unilateral hypoxic-ischaemic brain injury. Using
      moderate (15 min hypoxia) and severe (60 min hypoxia) models of hypoxic-ischaemia
      in juvenile rats and standard immunohistochemical techniques, we found intense
      growth hormone-like immunoreactivity present within regions of cell loss by 3
      days (P<0.05). Growth hormone-like immunoreactivity was observed on injured
      neurones, myelinated axons, glial cells within and surrounding infarcted tissue
      and on the choroid plexus plus ependymal cells within the injured hemisphere. The
      pattern of immunoreactivity suggests that (a) growth hormone (or a growth hormone
      like substance) is transported via the cerebrospinal fluid and (b) that growth
      hormone (or a growth hormone-like substance) is acting in a neurotrophic manner
      specifically targeted to injured neurones and glia. To test this hypothesis we
      treated a moderate hypoxic-ischaemic brain injury with 20 microg of rat growth
      hormone by intracerebroventricular infusion starting 2 h after injury
      (n=12/group). After 3 days the animals were killed and the extent of neuronal
      loss quantified. Growth hormone treatment reduced neuronal loss in the
      frontoparietal cortex (P<0.001), hippocampus (P<0.01) and dorsolateral thalamus
      (P<0.01) but not in the striatum. This spatial distribution of the
      neuroprotection conveyed by growth hormone correlates with the spatial
      distribution of the constitutive neural growth hormone receptor, but not with the
      neuroprotection offered by insulin-like growth factor-I treatment in this model.
      These results suggest that some of the neuroprotective effects of growth hormone
      are mediated directly through the growth hormone receptor and do not involve
      insulin-like growth factor-I induction.In summary, we have found that a growth
      hormone-like factor increased in the brain in the days after injury. In addition,
      treatment with growth hormone soon after an hypoxic-ischaemic injury reduced the
      extent of neuronal loss. These results further suggest that a neural growth
      hormone axis is activated during recovery from injury and that this may act to
      restrict the extent of neuronal death.

PMID- 11440802
TI  - Attention and visual interference stimulation affect somatosensory processing: a
      magnetoencephalographic study.
AB  - In our previous study, continuous visual (cartoon and random dot motion) and
      auditory (music) stimulation changed the somatosensory evoked magnetic fields
      following electrical stimulation of the median nerve in human subjects. They
      enhanced the middle-latency components (3M and 4M) generated in the contralateral
      primary somatosensory cortex, and reduced the MI component generated in the
      ipsilateral secondary somatosensory cortex. We speculated that such interference
      effects were caused by activation of polymodal neurons in areas 5 and/or 7 of the
      parietal lobe as well as in the medial superior temporal region and superior
      temporal sulcus. However, we could not exclude the effect of attention on such
      interference effects. In the present study, to know the effect of attention on
      visual and auditory interference in these changes, we stimulated the bilateral
      median nerves unilaterally in a random order, and asked subjects to count the
      number of times the left median nerve was stimulated while visual or auditory
      interference was applied. Five components (1M-5M) were identified in the
      hemisphere contralateral to the stimulated nerve and only one component (MI) was
      found in the ipsilateral hemisphere. The 3M and 4M components (33-75 ms in
      latency) were enhanced by both attention and visual interference stimulation but
      not by auditory stimulation. The 5M component (70-115 ms) and MI component (70
      133 ms) were enhanced by attention, but were not changed by attention together
      with visual or auditory interference. Summarizing the results of our previous
      study and the present study, (1) visual interference alone enhanced the 3M and 4M
      but reduced the MI, and (2) attention alone also enhanced the 3M and 4M, and
      enhanced the 5M and MI. As a result, (3) visual interference with attention
      enhanced the 3M and 4M more, and showed no significant change of the 5M and MI.
      This was compatible with a summation of the effects caused by visual interference
      alone and attention alone, but some interactions between visual interference and
      attention might have taken place. The locations of dipoles of all components were
      not significantly changed by attention or any interference stimulation. These
      findings support the idea that there are significant interactions of activities
      relating to somatosensory stimulation, visual stimulation and cognitive function,
      in both the primary and the secondary somatosensory cortex in humans.

PMID- 11440803
TI  - Sensorimotor experience modulates age-dependent alterations of the forepaw
      representation in the rat primary somatosensory cortex.
AB  - In a previous study, we found that the forepaw representation in the primary
      somatosensory cortex of rats housed in standard laboratory conditions was
      drastically altered during the aging process. In other studies we reported that
      exposure to an enriched environment improved the topographical organization and
      increased the spatial resolution of the forepaw cutaneous map in young adult
      rats, whereas housing in impoverished environment resulted in a loss of
      somatotopic details in the forepaw map. The main purpose of the present study was
      to investigate the influence of differential sensorimotor experience promoted by
      exposure to enriched or impoverished environments on the mutability of the
      cortical forepaw representation during aging. Two groups of Long-Evans rats were
      reared in enriched and impoverished environments from weaning to the age of 3.5-5
      months (young adults), 6.5-8 months (mature rats), and 23-28 months (senescent
      rats). The electrophysiological maps of the forepaw representation were based on
      the somatosensory 'submodality' (cutaneous vs. non-cutaneous), size, and location
      of the receptive fields of small clusters of layer IV neurons. Moreover, the
      mechanical thresholds of neuronal response to cutaneous stimulation were assessed
      with calibrated von Frey filaments in mature and senescent animals. Age-related
      alterations of the topographic features of the forepaw map were characterized by
      a decrease in and a fragmentation of the cortical zones serving the glabrous skin
      of the forepaw. These changes were less pronounced in the enriched rats than in
      the impoverished rats. Glabrous skin receptive fields were smaller in young adult
      and mature enriched rats than in their impoverished counterparts. However, during
      aging glabrous receptive fields increased in the enriched rats, but decreased in
      the senescent impoverished rats so that old rats of either groups displayed
      receptive fields of similar sizes; in contrast, the size of hairy skin receptive
      fields was not affected by housing conditions or aging. Measurement of the
      neuronal responses to calibrated forces applied to the skin indicated that
      cortical excitability to near-threshold cutaneous input was lower in senescent
      rats than in mature rats, regardless of environmental conditions. The present
      study demonstrates that use-dependent remodeling of somatosensory maps occurs
      throughout life and that environmental and social interactions can partially
      offset the age-related breakdown of somatosensory cortical maps.

PMID- 11440804
TI  - Interactions between environmental stimulation and antipsychotic drug effects on
      forebrain c-fos activation.
AB  - The immediate-early gene product Fos is differentially induced in the rat brain
      by the antipsychotic drugs haloperidol and clozapine. It is often claimed that
      although both drugs induce Fos in the nucleus accumbens, haloperidol but not
      clozapine increases Fos-like immunoreactivity in the striatum, whereas clozapine
      but not haloperidol increases Fos-like immunoreactivity in prefrontal cortex.
      Investigations of antipsychotic drug effects on Fos have typically administered
      high doses with pronounced sedative effects to behaviorally naive animals. In the
      present study, we compared the effects of low doses of haloperidol (0.1 mg/kg)
      and clozapine (5 mg/kg) on Fos-like immunoreactivity in rats which were either
      behaviorally naive, exposed to a novel environment or tested for two-way active
      avoidance. We determined that haloperidol increased Fos in the striatum and
      nucleus accumbens regardless of testing condition whereas clozapine markedly
      reduced the induction of Fos by behavioral testing in these regions; moreover,
      haloperidol dramatically increased prefrontal cortical Fos expression in animals
      placed in a novel environment, but not in testing-naive controls. From these
      results we suggest that antipsychotic drug-induced patterns of Fos expression in
      the rat are highly dependent on animals' concurrent behavioral status, perhaps
      reflecting neuroanatomically specific interactions between antipsychotic drugs
      and environmental stressors which also may occur in the schizophrenic condition.

PMID- 11440805
TI  - Adenosine, prolonged wakefulness, and A1-activated NF-kappaB DNA binding in the
      basal forebrain of the rat.
AB  - There is considerable evidence to suggest that adenosine is a modulator of
      behavioral state. Our previous reports showed that perfusion of adenosine into
      the basal forebrain decreased wakefulness. Furthermore, prolonged wakefulness
      resulted in increased levels of extracellular adenosine in the basal forebrain of
      cats and rats. However, the longer-term consequences of prolonged wakefulness and
      increased adenosine are largely unknown. We report here an increase in the DNA
      binding activity of the transcription factor, nuclear factor-kappa B (NF-kappaB)
      following 3 h of sustained wakefulness in the rat basal forebrain. Moreover, this
      treatment led to the appearance of the p65 subunit of NF-kappaB in the nucleus,
      as determined by western blot analysis of nuclear proteins. This contrasted with
      undetectable levels in the sleeping controls. A concomitant disappearance of I
      kappaB in cytoplasm suggested the degradation of this inhibitor of NF-kappaB. In
      the acute in vitro basal forebrain slice preparation, perfusion of adenosine
      increased NF-kappaB DNA binding while pretreatment of the slices with the A1
      adenosine receptor antagonist, cyclopentyl-1-3-dimethylxanthine, significantly
      reduced NF-kappaB DNA binding. These results are compatible with the hypothesis
      that increases in the levels of adenosine in the basal forebrain, that occur
      during prolonged wakefulness, act through an A1 adenosine receptor and a second
      messenger system to increase the activity of the transcription factor NF-kappaB.
      We further hypothesize that some of the long duration effects of prolonged
      wakefulness/sleep deprivation on performance and physiology, often termed 'sleep
      debt', might be mediated through adenosine and its activation of NF-kappaB, which
      is known to alter the expression of several behavioral state regulatory factors.

PMID- 11440806
TI  - Survival of dentate hilar mossy cells after pilocarpine-induced seizures and
      their synchronized burst discharges with area CA3 pyramidal cells.
AB  - The clinical and basic literature suggest that hilar cells of the dentate gyrus
      are damaged after seizures, particularly prolonged and repetitive seizures. Of
      the cell types within the hilus, it appears that the mossy cell is one of the
      most vulnerable. Nevertheless, hilar neurons which resemble mossy cells appear in
      some published reports of animal models of epilepsy, and in some cases of human
      temporal lobe epilepsy. Therefore, mossy cells may not always be killed after
      severe, repeated seizures. However, mossy cell survival in these studies was not
      completely clear because the methods did allow discrimination between mossy cells
      and other hilar cell types. Furthermore, whether surviving mossy cells might have
      altered physiology after seizures was not examined. Therefore, intracellular
      recording and intracellular dye injection were used to characterize hilar cells
      in hippocampal slices from pilocarpine-treated rats that had status epilepticus
      and recurrent seizures ('epileptic' rats). For comparison, mossy cells were also
      recorded from age-matched, saline-injected controls, and pilocarpine-treated rats
      that failed to develop status epilepticus. Numerous hilar cells with the
      morphology, axon projection, and membrane properties of mossy cells were recorded
      in all three experimental groups. Thus, mossy cells can survive severe seizures,
      and those that survive retain many of their normal characteristics. However,
      mossy cells from epileptic tissue were distinct from mossy cells of control rats
      in that they generated spontaneous and evoked epileptiform burst discharges. Area
      CA3 pyramidal cells also exhibited spontaneous and evoked bursts. Simultaneous
      intracellular recordings from mossy cells and pyramidal cells demonstrated that
      their burst discharges were synchronized, with pyramidal cell discharges
      typically beginning first. From these data we suggest that hilar mossy cells can
      survive status epilepticus and chronic seizures. The fact that mossy cells have
      epileptiform bursts, and that they are synchronized with area CA3, suggest a
      previously unappreciated substrate for hyperexcitability in this animal model.

PMID- 11440807
TI  - Analysis of high intracellular [Na+]-induced release of [3H]noradrenaline in rat
      hippocampal slices.
AB  - Our aim was to investigate the mechanisms involved in the high intracellular
      sodium-induced transmitter release in the CNS through the characterisation of the
      veratridine-evoked (40 microM) noradrenaline release from rat hippocampal slices.
      The response to veratridine was completely inhibited by tetrodotoxin (1 microM),
      indicating that the effect is due to the activation of sodium channels. Omission
      of Ca2+ from the superfusion fluid inhibited the veratridine-evoked release by
      72%, showing that the majority of release results from external Ca2+-dependent
      exocytosis. The residual Ca2+-independent release was not blocked by the
      intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic
      acid acetoxymethyl ester (100 microM) suggesting that intracellular Ca2+ stores
      are not involved in this component of veratridine effect. The noradrenaline
      uptake blockers, desipramine (10 microM) and nisoxetine (10 microM), inhibited
      the external Ca2+-independent release by 50 and 46%, respectively, indicating
      that the release partly originates from the reversal of transporters (carrier
      mediated release). In contrast to uptake blockers, lowering the temperature,
      another possibility to inhibit transporter function, completely inhibited the
      effect of veratridine in the absence of Ca2+. Further experiments revealed that
      low temperature (20 and 12 degrees C) reduces the veratridine-induced increase of
      intracellular sodium concentration ([Na+]i) in rat cortical synaptosomes (68 and
      78% inhibition, respectively). The clinical relevance of our data is that during
      ischemia a massive release of transmitters occurs mainly due to the elevation of
      [Na+]i, which contributes to the development of ischemic brain injury. Our
      results show that low temperature may be a better therapeutic approach to the
      treatment of ischemia because it has a dual action on this process. Firstly, it
      inhibits the function of uptake transporters and hence reduces the carrier
      mediated outflow of transmitters. Secondly, it inhibits the sodium influx and
      therefore prevents the unwanted elevation of [Na+]i. Our data also suggest that
      veratridine stimulation can be a suitable model for ischemic conditions.

PMID- 11440808
TI  - Ethanol pre-exposure suppresses HIV-1 glycoprotein 120-induced neuronal
      degeneration by abrogating endogenous glutamate/Ca2+-mediated neurotoxicity.
AB  - The neurotoxic mechanism of HIV-1 envelope glycoprotein 120 (gp120) involves
      glutamatergic (NMDA) receptor/Ca2+-dependent excitotoxicity, mediated in part via
      glia. Pro-inflammatory cytokines also may have roles. We have reported that pre
      exposure of brain cultures to 'physiological' ethanol concentrations (20-30 mM)
      protects against neuronal damage from HIV-1 gp120, but not from the direct
      receptor agonist, NMDA. Using lactate dehydrogenase assays and propidium iodide
      staining of rat organotypic hippocampal-entorhinal cortical slice cultures we
      determined that ethanol's suppression of gp120 neurotoxicity required at least 4
      days of pretreatment. The gp120-induced neurotoxicity was accompanied by
      interleukin-6 elevations that were not affected by the pretreatment. However,
      gp120 induced substantial, early increases in extracellular glutamate levels that
      were blocked by ethanol pretreatment, conceivably abrogating excitotoxicity.
      Consistent with abrogation of excitotoxic pathways, fura-2 imaging showed
      selective deficits in gp120-dependent intracellular Ca2+ responses in ethanol
      pretreated slices. Gp120 is believed to increase glutamate levels by both
      stimulating release and inhibiting (re)uptake. Results with a labeled glutamate
      analog, D-[3H]aspartate, revealed that gp120's inhibition of glutamate uptake,
      rather than its stimulation of release, was abolished after ethanol. Further
      studies indicated that two converging effects of ethanol pretreatment may
      underlie the abolishment of gp120-mediated glutamate uptake inhibition: (a)
      blockade of gp120-induced release (ostensibly from glia) of arachidonic acid, an
      inhibitor of astroglial glutamate reuptake, and (b) modest proliferation and
      activation of astroglia upon gp120 stimulation--which are likely to augment
      glutamate transporters. Thus, as with gp120 itself, glia and
      glutamate/arachidonic acid regulation appear to be important targets for ethanol.
      Since moderate ethanol consumption is as common among HIV-infected individuals as
      in the general population, this newly recognized neuroprotective (and apparently
      anti-excitotoxic) effect of ethanol withdrawal in vitro could be important, but
      it requires further study before its significance, if any, is understood.

PMID- 11440809
TI  - Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes
      dendritic growth and calbindin phenotype in cultured rat striatal neurons.
AB  - Bone morphogenetic proteins are members of the transforming growth factor-beta
      superfamily. They are widely expressed in the mammalian nervous system, where
      they exert trophic effects on several neuronal populations. We studied the
      neurotrophic activity of bone morphogenetic protein-2 and bone morphogenetic
      protein-7 (also called osteogenic protein-1) on cultured striatal cells,
      previously shown to express bone morphogenetic protein ligands and receptors. Our
      results indicate that only bone morphogenetic protein-2 promoted the
      differentiation of GABAergic neurons, especially of the calbindin-positive
      subpopulation, the subset of projecting striatal neurons that degenerates in
      Huntington's disease. Bone morphogenetic protein-2 increased the area, perimeter
      and degree of arborization of GABAergic neurons, promoting calbindin phenotype
      without altering proliferation or apoptosis. In contrast, neither bone
      morphogenetic protein-2 nor -7 affected striatal cholinergic interneurons.
      However, they both increased the number of glial fibrillary acidic protein
      positive cells. Suppression of glial proliferation with 5-fluorodeoxyuridine did
      not abolish bone morphogenetic protein-2 effects on the differentiation of
      striatal neurons, ruling out an indirect mechanism through astrocytes. In
      conclusion, our results show that bone morphogenetic protein-2 promotes the
      differentiation of cultured GABAergic striatal neurons, suggesting that bone
      morphogenetic proteins are involved in the development of the striatum.

PMID- 11440810
TI  - Nucleus accumbens muscarinic receptors in the control of behavioral depression:
      antidepressant-like effects of local M1 antagonist in the Porsolt swim test.
AB  - Systemically administered cholinomimetics or cholinesterase inhibitors can
      depress behavior in humans and animals, whereas antimuscarinic agents reverse
      this effect or even produce euphoria. Although these effects have been well
      documented, the specific brain regions that mediate them remain largely unknown.
      In the present experiments, muscarinic agonists and antagonists were locally
      injected into the nucleus accumbens of female Sprague-Dawley rats to test for
      their effects on behavioral depression in the Porsolt swim test and locomotor
      activity. Local, microinjections of the drugs in the accumbens elicited behaviors
      that were similar to the systemic effects reported in other studies. Injection of
      the non-specific agonist arecoline (40 and 80 microg) dose-dependently inhibited
      swimming and escape behavior. This may be mediated in part by accumbens M1
      receptors because blocking these receptors with the specific antagonist
      pirenzepine (17.5 and 35.0 microg) did the opposite by increasing swimming.
      Gallamine (0.13, 0.44, and 0.88 microg), an antagonist at M2 receptors, dose
      dependently decreased swimming. Two-way microdialysis suggested that this was in
      part due to the release of ACh by blocking M2 autoreceptors. Scopolamine, a mixed
      M1/M2 receptor antagonist, also released ACh but did not decrease swimming,
      probably because the M1 receptors were blocked; the drug (1.0 microg) increased
      swimming time, much like pirenzepine. With the exception of arecoline, none of
      the drugs significantly affected locomotor activity in a photocell cage.
      Arecoline (40 microg), which had decreased swimming, reduced activity. The
      present study suggests that muscarinic receptors in the nucleus accumbens can
      control immobility in the Porsolt swim test. The onset of immobility may depend
      on the activation of post-synaptic M1 receptors.

PMID- 11440811
TI  - Neuropeptide Y Y1 receptor-mediated anxiolysis in the dorsocaudal lateral septum:
      functional antagonism of corticotropin-releasing hormone-induced anxiety.
AB  - Neuropeptide Y and corticotropin-releasing hormone are involved in the regulation
      of various physiological functions including the expression of anxiety and fear.
      The anxiogenic effects of corticotropin-releasing hormone can be modulated by
      neuropeptide Y, yet the brain regions involved in this interaction are only
      partly understood. By utilizing antibodies raised against neuropeptide Y and the
      Y1 receptor protein we identified a densely labeled cell group in the dorsal zone
      of caudal part of the rat lateral septum. Bilateral microinjections of
      neuropeptide Y into the dorsocaudal lateral septum but not into the intramedial
      septum dose-dependently decreased anxiety in the social interaction test of rats,
      whereas the effects of corticotropin-releasing hormone were opposite. The
      anxiogenic-like effect of corticotropin-releasing hormone was reversed by
      neuropeptide Y pretreatment. Local microinjection of the neuropeptide Y receptor
      selective antagonists revealed that neither Y1 receptor nor Y2 receptor selective
      antagonists had effects on experimental anxiety on their own suggesting that
      neuropeptide Y-induced anxiolysis is not tonic. The Y1 receptor antagonist
      blocked the anxiolytic-like effect of neuropeptide Y, while the Y2 receptor
      antagonist was ineffective.We conclude that neuropeptide Y in the dorsocaudal
      lateral septum may act as an endogenous anxiolytic and antagonize corticotropin
      releasing hormone (stress)-induced anxiety. This functional antagonism probably
      shapes behavior under aversive conditions, as neuropeptide Y-induced anxiolysis
      is not tonic in nature. An imbalance between these two neuropeptide systems in
      the septum may lead to a maladaptive expression of anxiety after stress exposure.

PMID- 11440812
TI  - Bed nucleus of the stria terminalis and extended amygdala inputs to dopamine
      subpopulations in primates.
AB  - The 'extended amygdala', a forebrain continuum implicated in complex motivational
      responses, is comprised of the bed nucleus of the stria terminalis and its
      sublenticular extension into the centromedial amygdala. Dopamine is also involved
      in motivated behavior, and is increased in several brain regions by emotionally
      relevant stimuli. To examine how the extended amygdala influences the dopamine
      cells, we determined the organization of inputs from subdivisions of the bed
      nucleus of the stria terminalis and sublenticular extended amygdala to the
      dopamine subpopulations in monkeys. Inputs from the bed nucleus of the stria
      terminalis and corresponding regions of the sublenticular extended amygdala are
      differentially organized. The medial bed nucleus of the stria terminalis and its
      medial sublenticular extension have a mediolateral organization with the densest
      inputs to the medial substantia nigra, pars compacta, and relatively few inputs
      to the central and lateral substantia nigra. In contrast, the lateral bed nucleus
      of the stria terminalis (and its continuation into the sublenticular extended
      amygdala) projects across the mediolateral extent of the substantia nigra. The
      subnuclei of the lateral bed nucleus of the stria terminalis also have
      differential projections to the dopamine cells. While the central core of the
      lateral bed nucleus of the stria terminalis has restricted inputs, the
      surrounding dorsolateral, capsular and juxtacapsular subdivisions project
      strongly to the dorsal tier dopamine neurons. The posterior subdivision of the
      lateral bed nucleus of the stria terminalis and its continuation into the central
      sublenticular extended amygdala project more broadly to both the dorsal tier and
      densocellular region of the ventral tier. From these results we suggest that
      specific subdivisions of the bed nucleus of the stria terminalis have
      differential influences on the dopamine subpopulations, influencing dopamine
      responses in diverse brain regions.

PMID- 11440813
TI  - Apamin-induced irregular firing in vitro and irregular single-spike firing
      observed in vivo in dopamine neurons is chaotic.
AB  - Dopamine neurons of the substantia nigra often fire action potentials irregularly
      in vivo, but in vitro fire in a regular, pacemaker-like firing pattern. Bath
      application of apamin, a blocker of calcium-activated potassium channels, can
      shift a dopamine neuron from pacemaker-like to irregular firing. To determine
      whether the irregular firing was caused by intrinsic cellular mechanisms rather
      than random synaptic input or some other form of noise, spike density functions
      of interspike interval records were analyzed using non-linear forecasting methods
      to quantify any non-linear (non-periodic) structure. Intrinsic cellular
      mechanisms are capable of producing chaotic firing, which is deterministic, non
      linear, and loses predictability exponentially with increasing forecast time.To
      determine whether forecasting spike density functions could reliably measure
      predictability, forecasting was first applied to spike density functions produced
      by computer simulations of pacemaker-like, chaotic, and random firing, as well as
      pacemaker-like and chaotic firing that were randomly synaptically driven.
      Exponential loss of predictability was successfully detected in both chaotic and
      randomly driven chaotic firing. Predictability scaled faster than exponentially
      for random spiking, and linearly (slower than exponentially) for randomly driven
      pacemaker firing. The method was then applied to experimental records of apamin
      induced irregular firing of rat dopaminergic neurons of the substantia nigra in
      vitro and in vivo. Exponential loss of predictability was detected in both cases,
      consistent with chaotic firing. Experimental records of pacemaker-like firing in
      vitro showed linear scaling, consistent with a randomly driven pacemaker. Several
      schemes for neural encoding of synaptic inputs have been suggested, such as rate
      codes or temporal codes. However, our results suggest that under some conditions,
      the irregular firing of dopamine neurons does not reflect the random temporal
      dynamics of its inputs, but rather the intrinsic, deterministic dynamics of
      dopamine cells themselves, under the tonic neuromodulatory influence of apamin in
      vitro and possibly that of an unidentified endogenous modulatory substance in
      vivo.

PMID- 11440814
TI  - Neurons of origin of the neurotensinergic plexus enmeshing the ventral tegmental
      area in rat: retrograde labeling and in situ hybridization combined.
AB  - The morphological and physiological substrates that underlie the mutual
      regulatory interactions of neurotensin and dopamine in the rat mesotelencephalic
      projections and related structures remain to be fully described. A salient
      candidate for neurotensinergic effects on the mesotelencephalic dopamine
      projection is the dense plexus of neurotensin immunoreactive axons that enmeshes
      the ventral tegmental area and substantia nigra, but the locations of the neurons
      that give rise to this plexus have not been identified and its systemic context
      remains obscure. To address this, Fluoro-Gold and the cholera toxin beta subunit,
      retrogradely transported axonal tracers, were injected into the ventral tegmental
      area of rats and the brains were processed to demonstrate neurons that contained
      both retrograde tracer immunoreactivity and a probe against
      neurotensin/neuromedin N messenger RNA. Substantial numbers of double-labeled
      neurons were observed in the rostral part of the lateral septum, and in a region
      centered on the shared boundaries of the bed nucleus of stria terminalis,
      ventromedial ventral pallidum, diagonal band of Broca, lateral preoptic area and
      rostral lateral hypothalamus. A few double-labeled neurons were also observed in
      the dorsal raphe nucleus and adjacent periaqueductal gray. Despite the
      administration of haloperidol and D-amphetamine to elicit and enhance
      neurotensin/neuromedin N messenger RNA expression in striatum, including the
      nucleus accumbens and olfactory tubercle, no double-labeled neurons were observed
      there. These results identify a novel brain substrate for control of midbrain
      dopamine levels, which affect reward mechanisms and motivation.

PMID- 11440815
TI  - Spatial distribution of the vestibulospinal neurons in the frog vestibular
      nuclei.
AB  - In experiments on the preparation of a frog perfused brain (Rana ridibunda),
      intracellular potentials were recorded from neurons of the vestibular nuclei
      following stimulation of the vestibular nerve and the spinal cord. The
      vestibulospinal neurons were identified on the basis of excitatory postsynaptic
      potentials evoked by the stimulation of the ipsilateral vestibular nerve and
      antidromic activation from the stimulation of the cervical and lumbar
      enlargements of the spinal cord. The cells that could be activated antidromically
      only by cervical cord stimulation have been designated as C cells, and the cells
      that could also be activated antidromically as a result of lumbar stimulation
      have been termed L cells. The average conduction velocity determined for C
      neurons was 10.67 m/s and for L neurons 15.84 m/s. The ratio of C and L neurons
      over the vestibular nuclear complex was very similar to each other: 52% C neurons
      and 48% L neurons. The majority of both types of neurons were localized in the
      lateral vestibular nucleus (58.6%), to a lesser extent in the descending
      vestibular nucleus (30.7%) and very little in the medial vestibular nucleus
      (10.6%). In the lateral vestibular nucleus, C neurons prevailed in the caudal
      part of the nucleus and L neurons prevailed in the rostral part. By contrast, in
      the descending and medial vestibular nuclei there was a gradual increase of C and
      L cells quantitatively from the rostral to the caudal part. Fast and slow cells
      were detected among the vestibulospinal neurons. The fast neurons of L cells did
      not prevail greatly over the slow ones, whereas the slow neurons of C cells
      prevailed comparatively largely over the fast neurons. Thus, it became possible
      to reconstruct the spatial distribution of the identified vestibulospinal
      neurons. The results of spatial distribution of C and L vestibulospinal neurons
      in the frogs failed to conform to definite somatotopy, which is characteristic of
      mammalian vestibular nuclei. The results of this study have confirmed an earlier
      assumption that C and L neurons in the frog's vestibular nuclei as a source of
      vestibulospinal fibers, are scattered separately or more frequently in groups, so
      that they establish a 'patch-like' somatotopy and do not form a distinctly
      designed field as in mammals.

PMID- 11440816
TI  - The role of kainic acid/AMPA and metabotropic glutamate receptors in the
      regulation of opioid mRNA expression and the onset of pain-related behavior
      following excitotoxic spinal cord injury.
AB  - Intraspinal injection of quisqualic acid, a mixed kainic acid/2-amino-3(3-hydroxy
      5-methylisoxazol-4-yl)propionic acid and metabotropic glutamate receptor agonist,
      produces an excitotoxic injury that leads to the onset of both spontaneous and
      evoked pain behavior as well as changes in spinal and cortical expression of
      opioid peptide mRNA, preprodynorphin and preproenkephalin. What characteristics
      of the quisqualic acid-induced injury are attributable to activation of each
      receptor subtype is unknown. This study attempted to define the role of
      activation of the kainic acid/2-amino-3(3-hydroxy-5-methylisoxazol-4-yl)propionic
      acid (AMPA) and metabotropic glutamate receptor subtypes in the regulation of
      opioid peptide expression and the onset of spontaneous and evoked pain-related
      behavior following excitotoxic spinal cord injury by comparing quisqualic acid
      induced changes with those created by co-injection of quisqualic acid and the
      kainic acid/AMPA antagonist, 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo[f]quinoxaline, (NBQX) or the metabotropic antagonist, (RS)-1
      aminoindan-1,5-dicarboxylic acid (AIDA). Therefore, 42 male Long-Evans adult rats
      were divided into seven treatment groups and received intraspinal microinjections
      of saline (sham), 0.5% dimethylsulphoxide (sham), quisqualic acid (1.2 microl,
      125 mM), NBQX (1.2 microl, 60 microM), AIDA (1.2 microl, 250 microM), quisqualic
      acid/NBQX (1.2 microl, 125 mM/60 microM), or quisqualic acid/AIDA (1.2 microl,
      125 mM/250 microM) directed at spinal levels thoracic 12-lumbar 2. Behavioral
      observations of spontaneous and evoked pain responses were completed following
      surgery. After a 10-day survival period, animals were killed and brain and spinal
      cord tissues were removed and processed for histologic analysis and in situ
      hybridization. Both AIDA and NBQX affected the quisqualic acid-induced total
      lesion volume but only AIDA caused a decrease in the percent tissue damage at the
      lesion epicenter. Preprodynorphin and preproenkephalin expression is increased in
      both spinal and cortical areas in quisqualic acid-injected animals versus sham-,
      NBQX or AIDA-injected animals. NBQX did not affect quisqualic acid-induced spinal
      or cortical expression of preprodynorphin or preproenkephalin except for a
      significant decrease in preproenkephalin expression in the spinal cord. In
      contrast, AIDA significantly decreases quisqualic acid-induced preprodynorphin
      and preproenkephalin expression within the spinal cord and cortex. AIDA, but not
      NBQX, significantly reduced the frequency of, and delayed the onset of,
      quisqualic acid-induced spontaneous pain-related behavior. From these data we
      suggest that both the kainic acid/AMPA and metabotropic glutamate receptor
      subtypes are involved in the induction of the excitotoxic cascade responsible for
      quisqualic acid-induced neuronal damage and changes in opioid peptide mRNA
      expression, while metabotropic glutamate receptors may play a more significant
      role in the onset of post-injury pain-related behavior.

PMID- 11440817
TI  - Hyperalgesia induced by peripheral inflammation is mediated by protein kinase C
      betaII isozyme in the rat spinal cord.
AB  - We have addressed the molecular mechanism(s) of hyperalgesia, which depends on
      increased excitability of dorsal horn neurons and on sensitization of primary
      afferent nociceptors, during peripheral inflammation. Following unilateral
      adjuvant-induced inflammation in the rat hind paw, time-course changes in
      behavioral hyperalgesia and functional activities of Ca2+/phospholipid-dependent
      protein kinase C isozymes were examined. Inflammation was characterized by
      increase in paw diameter, and behavioral hyperalgesia was quantified as paw
      withdrawal latency from a radiant heat source. Behavioral hyperalgesia on the
      injected paw was significantly increased. This was accompanied by a significant
      increase in total functional membrane-associated protein kinase C activity,
      whereas total cytosolic protein kinase C activity was unchanged on the sides of
      the lumbar spinal cord both contralateral and ipsilateral to the inflammation.
      Importantly, on the side of lumbar cord ipsilateral to the inflamed paw, the
      activity of membrane-associated protein kinase CbetaII was increased following
      the same time-course as the paw withdrawal latency decrease, suggesting an
      increased translocation of protein kinase Cbetall to the membrane related to
      behavioral hyperalgesia. A defined mixture of purified gangliosides, which
      inhibits intracellular protein kinase C translocation and activation, decreased
      inflammation-induced paw withdrawal latency, and specifically decreased the
      activity of membrane-associated protein kinase Cbetall on the side of the spinal
      cord ipsilateral to the inflammation. Quantitative immunohistochemical analyses
      demonstrated intensified protein kinase CbetaII-like immunoreactivity on the side
      of the spinal cord ipsilateral to the inflammation. Time-course for increases in
      the activity of membrane-associated protein kinase CbetaII, and in intensity of
      protein kinase CbetaII-immunoreactivity, paralleled inflammation-mediated changes
      in paw withdrawal latency and paw diameter. Our findings indicate an apparent
      involvement of protein kinase CbetaII isozyme specifically in the molecular
      mechanism(s) of thermal hyperalgesia.

PMID- 11440818
TI  - Fibroblast growth factor-5 is expressed in Schwann cells and is not essential for
      motoneurone survival.
AB  - Fibroblast growth factor-5 (FGF-5) is a putative target-derived survival factor
      for motoneurones as it is concentrated in the synaptic portions of skeletal
      muscles and because it promotes the survival of embryonic motoneurones in vitro.
      A variety of experimental approaches have been used to examine this possibility.
      The expression of FGF-5 in the neuromuscular system was analysed using the
      reverse transcription-polymerase chain reaction (RT-PCR). Both splice variants of
      FGF-5 were detected in adult rat skeletal muscle, sciatic nerve, and spinal cord.
      The expression of FGF-5 in skeletal muscle was up-regulated after denervation. At
      first sight this appears to be consistent with FGF-5 being a target-derived
      factor. However, FGF-5 protein was detected in Schwann cells, macrophages,
      vascular smooth muscle and endothelial cells, but not in muscle fibres. The
      absence of FGF-5 in muscle fibres was confirmed by RT-PCR examination of isolated
      muscle fibres. Furthermore, FGF-5 protein was also not detected in denervated
      fibres, as would be expected for a neuronal survival factor. Denervation did
      however lead to up-regulation of FGF-5 in the Schwann cells of the distal nerve
      trunk. This may indicate that FGF-5 is either an autocrine regulator of Schwann
      cells or a Schwann cell-derived neurotrophic factor. The latter appears not to be
      the case for two reasons. First, the double-ligation technique was used to show
      that endogenous FGF-5 is not transported in motor axons. Second, stereological
      estimates of the number of motoneurones in an FGF-5 null mutant (Angora) mouse
      failed to reveal any loss of motoneurones. Collectively these experiments suggest
      that FGF-5 is not a physiological regulator of motoneurones, and therefore raise
      the possibility that it is an autocrine regulator of Schwann cells.

PMID- 11440819
TI  - Alpha-synuclein-enhanced green fluorescent protein fusion proteins form
      proteasome sensitive inclusions in primary neurons.
AB  - Alpha-synuclein accumulates in the brains of sporadic Parkinson's disease
      patients as a major component of Lewy bodies, and mutations in alpha-synuclein
      are associated with familial forms of Parkinson's disease. The pathogenic
      mechanisms that precede and promote the aggregation of alpha-synuclein into Lewy
      bodies in neurons remain to be determined. Here, we constructed a series of alpha
      synuclein-enhanced green fluorescent protein (alpha-synucleinEGFP, SynEGFP)
      fusion proteins to address whether the Parkinson's disease-associated mutations
      alter the subcellular distribution of alpha-synuclein, and to use as a tool for
      experimental manipulations to induce aggregate formation. When transfected into
      mouse cultured primary neurons, the 49-kDa alpha-synucleinEGFP fusion proteins
      are partially truncated to a approximately 27-kDa form. This non-fluorescent
      carboxy-terminally modified fusion protein spontaneously forms inclusions in the
      neuronal cytoplasm. A marked increase in the accumulation of inclusions is
      detected following treatment with each of three proteasome inhibitors, n-acetyl
      leu-leu-norleucinal, lactacystin and MG132. Interestingly, Ala30Pro alpha
      synucleinEGFP does not form the cytoplasmic inclusions that are characteristic of
      wild-type and Ala53Thr alpha-synucleinEGFP, supporting the idea that the Ala30Pro
      alpha-synuclein protein conformation differs from wild-type alpha-synuclein.
      Similar inclusions are formed if alpha-synuclein carboxy-terminus is modified by
      the addition of a V5/6xHistidine epitope tag. By contrast, overexpression of
      unmodified alpha-synuclein does not lead to aggregate formation. Furthermore,
      synphilin-1, an alpha-synuclein interacting protein also found in Lewy bodies,
      colocalizes with the carboxy-terminally truncated alpha-synuclein fusion protein
      in discrete cytoplasmic inclusions.Our finding that manipulations of the carboxy
      terminus of alpha-synuclein lead to inclusion formation may provide a model for
      studies of the pathogenic mechanisms of alpha-synuclein aggregation in Lewy
      bodies.

PMID- 11440820
TI  - Ethanol blocks cytosolic Ca2+ responses triggered by activation of GABA(A)
      receptor/Cl- channels in cultured proliferating rat neuroepithelial cells.
AB  - GABA(A) receptor/Cl- channels and voltage-gated Ca2+ channels are believed to be
      important sites of ethanol action in the CNS. Acute exposure of ethanol
      potentiates GABA(A) receptor/Cl- channel activity and inhibits voltage-gated Ca2+
      channels in a number of preparations, mostly post-mitotic neurons. The effects of
      ethanol on these channels in primary cultures of undifferentiated neural
      precursor cells remain unknown. To address this issue, we examined the effects of
      ethanol on GABA(A) agonist-activated elevation of cytosolic Ca2+ in an in vitro
      model of the cortical neuroepithelium derived from rat basic fibroblast growth
      factor-expanded neural precursor cells. We found a potent inhibition of GABA(A)
      activated elevation of cytosolic Ca2+ by ethanol in actively proliferating cells.
      Since we had recently demonstrated that GABA(A) receptor activation depolarizes
      these cells and elevates their cytosolic Ca2+, we tested whether the effects of
      ethanol involved both GABA(A) receptors and voltage-gated Ca2+ channels. Both
      extracellular K+- and muscimol-induced cytosolic Ca2+ elevations were abolished
      by nitrendipine, indicating that both depolarizing stimuli triggered Ca2+ influx
      through L-type voltage-gated Ca2+ channels. Exposure of proliferating cells to
      different concentrations of ethanol revealed that the drug was more potent in
      blocking muscimol-induced compared to K+-evoked cytosolic Ca2+ elevations. These
      results raise the possibility that ethanol blocks GABAergic stimulation of
      cytosolic Ca2+ levels in proliferating precursors primarily by interacting with
      GABA(A) receptor/Cl- channels and secondarily with voltage-gated Ca2+ channels.

PMID- 11440821
TI  - Fetal growth restriction is not associated with a reduced risk for bilateral
      spastic cerebral palsy in very-low-birthweight infants.
AB  - OBJECTIVE: To evaluate the influence of confounding and sampling bias on the
      relationship between fetal growth restriction in a very-low-birthweight-defined
      cohort (VLBW, < or =1500 g) and bilateral spastic cerebral palsy (BSCP) at early
      school-age. METHODS: Three hundred twenty-four of 407 long-term survivors of a
      regional cohort of VLBW newborns were followed until age 6 years. We categorized
      as small for gestational age (SGA) all infants whose birthweight Z-score was
      below -2 relative to published reference values. Uni- and multivariable logistic
      regression models were fit to estimate the risk of BSCP associated with SGA in
      the total sample, in subsamples defined by gestational age, and in a gestational
      age-matched case-control sample. RESULTS: In the total sample, no child below 28
      weeks was SGA, and no child above 32 weeks had an appropriate birthweight for
      gestational age (AGA). The prevalence of BSCP was 14% in AGA and 2% in SGA
      infants. In both uni- and multivariable logistic regression analyses of the total
      sample, SGA was associated with a prominently reduced risk of BSCP (odds ratios
      range from 0.1 to 0.2, all 95% confidence limits exclude 1.0). However, analyses
      performed in samples defined by different gestational age cutoffs (24--31 weeks,
      28--31 weeks) and in a sample using three gestational age-matched controls per
      BSCP-case did not show a protection by growth restriction (odds ratios range from
      0.8 to 2.2, all 95% confidence limits include 1.0). CONCLUSIONS: In VLBW-defined
      samples, the apparent protective effect of SGA for BSCP can be explained, at
      least in part, by the highly skewed distribution of SGA over the available
      gestational age range. From this follows that study cohorts should be defined by
      gestational age and not by birthweight. In distorted samples like this one, even
      controlling for gestational age does not reduce the illusion of a reduced
      cerebral palsy risk for growth restricted infants. Only restriction of the sample
      by gestational age and/or matching for gestational age reveals the absence of
      this apparent protective effect.

PMID- 11440822
TI  - Developmental outcomes and environmental correlates of very low birthweight,
      cocaine-exposed infants.
AB  - Fetal cocaine exposure may have differentially adverse effects on developmental
      outcomes of very low birthweight (VLBW) infants. As part of a longitudinal study,
      31 cocaine-positive very low birthweight infants, and age, race and socioeconomic
      status matched VLBW controls enrolled at birth were followed. Neonatal maternal
      child interactions, concurrent maternal psychological characteristics and
      environmental factors conceptualized as important for child outcome were assessed
      as well as standard developmental outcomes at 3 years. In the neonatal period,
      cocaine-exposed VLBW infants who remained in maternal custody tended to be rated
      as less responsive and their mothers as less nurturing, less emotionally
      available and with a tendency to use more maladaptive coping mechanisms than
      nonexposed VLBW infants. At follow-up, cocaine-exposed VLBW children were delayed
      in cognitive, motor and language development compared to controls. Almost half
      (45%) of the exposed children scored in the range of mental retardation compared
      to 16% of the comparison VLBW children. The persistent cognitive, motor and
      language delays of the cocaine-exposed VLBW children, combined with the poorer
      behavioral interactions of cocaine-using women with their infants in the neonatal
      period, indicate a need for increased developmental surveillance of cocaine
      exposed VLBW infants with a focus on maternal drug treatment and parenting
      interventions.

PMID- 11440823
TI  - Mechanisms for differences in monozygous twins.
AB  - Monozygous (MZ) twins are often described as being physically and genetically
      identical. Clinical determination of zygosity relies on the assumption that any
      physical differences between a pair of twins imply they are dizygous. Most twin
      research relies on the assumption that dizygous twins share approximately 50% of
      the same genes, whereas monozygous twins share 100%. There is, however,
      increasing evidence to challenge both these assumptions. In this review, we
      describe a number of intrauterine effects and genetic mechanisms that may result
      in phenotypic, genotypic, and epigenetic differences between monozygous twins.
      Newer molecular techniques are resulting in such differences being increasingly
      commonly recognised. The potential for differences in monozygotic twin pairs is
      an important consideration for both clinicians and researchers involved in twin
      work.

PMID- 11440824
TI  - Growth-restricted premature infants are at increased risk for low thyroxine.
AB  - OBJECTIVE: To evaluate, in extremely premature infants, the relationship between
      growth restriction and early total thyroxine levels, and to determine how
      maternal, prenatal, perinatal and neonatal variables influence the relationship.
      STUDY DESIGN: 719 infants born at four medical centers in Massachusetts, New York
      and New Jersey between 1991 and 1993 were studied. Entry criteria included:
      gestational age 23--30 weeks, birth weight 500--1500 g, and a serum thyroxine
      level obtained in the first week of life. Infants born to mothers with a history
      of thyroid disease were excluded. Birth weight and total thyroxine level are
      expressed as z-scores (standard deviation units) to adjust for their relationship
      to gestational age. RESULTS: In linear regression analysis, there was a 0.18
      decrease in the total thyroxine z-score for each 1.0 (1 standard deviation unit)
      decrease in birth weight z-score (p=0.0001). Adjustment for multiple potential
      maternal, prenatal, perinatal and neonatal confounders failed to identify a
      factor or factors that could account for the observed association. CONCLUSIONS:
      The early total thyroxine level in extremely preterm infants was significantly
      associated with birth weight z-score. This relationship persisted even after
      adjustment for maternal, prenatal, perinatal and neonatal confounders suggesting
      antenatal influences. Of clinical importance, growth-restricted infants are at
      increased risk for early hypothyroxinemia and, possibly, to its related
      morbidities.

PMID- 11440825
TI  - MOS HIP: McMaster outcome study of hypertension in pregnancy.
AB  - BACKGROUND: The offspring of women with hypertension during pregnancy are at
      increased risk of low birthweight, preterm birth, diseases of prematurity and
      death. The risk of developing these outcomes among women with either preeclampsia
      or chronic hypertension, relative to those with gestational hypertension, is not
      known. STUDY DESIGN: Prospective cohort study. PARTICIPANTS: A total of 1948
      singleton women seen at a large tertiary care obstetrical center, whose blood
      pressure was greater than 140/90 mm Hg during pregnancy. The four types of
      hypertension were strictly defined: 864 women (44.4%) had gestational
      hypertension, 459 (23.6%) isolated chronic hypertension, 501 (25.7%) isolated
      preeclampsia, and 124 (6.4%) chronic hypertension with superimposed preeclampsia.
      OUTCOME MEASURES: The primary outcome of the study was a composite of the
      diseases of prematurity, need for assisted ventilation for greater than 1 day, or
      perinatal death. The secondary outcomes were each of those included in the
      primary endpoint, as well as admission to the neonatal ICU, small for gestational
      age (SGA) birthweight and preterm birth. We controlled for the effects of other
      maternal risk factors, such as age, parity, history of preterm delivery,
      cigarette smoking, pre-pregnancy weight, diabetes mellitus (DM), renal
      dysfunction, and current use of an antihypertensive agent or prednisone. RESULTS:
      For the primary composite outcome, compared to the offspring of women with
      gestational hypertension, the adjusted odds ratio was 1.9 (95% confidence
      interval 1.2 to 3.0) in the preeclamptic group and 2.0 (95% confidence interval
      1.0 to 4.0) for those with chronic hypertension plus superimposed preeclampsia.
      Those with preeclampsia were at increased risk for small for gestational age
      birthweight (odds ratio 2.2, 95% confidence interval 1.5 to 3.1), as were the
      offspring of mothers who had chronic hypertension with superimposed preeclampsia
      (odds ratio 2.1, 95% confidence interval 1.2 to 3.8). Similarly, the rate of
      preterm birth before 32 weeks was highest among the infants of both preeclamptic
      mothers (28.5%; odds ratio 4.7, 95% confidence interval 2.9 to 7.6) and those
      with chronic hypertension and preeclampsia (30.5%; odds ratio 3.5, 95% confidence
      interval 1.8 to 6.7). The perinatal mortality rate was highest in the group of
      women with chronic hypertension plus preeclampsia (9.2%; odds ratio 3.2, 95%
      confidence interval 1.2 to 9.1). Other significant risk factors for the primary
      composite outcome included previous preterm delivery (odds ratio 2.7, 95%
      confidence interval 1.4 to 5.2), smoking (odds ratio 1.8, 95% confidence interval
      1.1 to 3.0) and use of an antihypertensive agent during pregnancy (odds ratio
      1.8, 95% confidence interval 1.2 to 2.7). Prednisone use was strongly associated
      with risk for perinatal death (odds ratio 4.9, 95% confidence interval 1.4 to
      17.1). CONCLUSIONS: Relative to women with isolated gestational hypertension,
      those who develop preeclampsia, either with or without underlying chronic
      hypertension, experience worse perinatal outcomes. A history of previous preterm
      delivery and maternal smoking increase the rate preterm birth and major perinatal
      disease. Antihypertensive and prednisone therapy may be important risk factors
      for adverse perinatal events, but further research is needed to confirm these
      findings.

PMID- 11440826
TI  - Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated
      massive genomic DNA fragmentation and apoptotic cell death.
AB  - Diclofenac (DCLF) is a nonsteroidal anti-inflammatory drug that is widely used
      for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing
      spondylitis, and acute muscle pain conditions. Toxic doses of DCLF can cause
      nephrotoxicity in humans and experimental animals. However, whether this DCLF
      induced nephrotoxicity involves apoptotic cell death in addition to necrosis is
      unknown. The goals of this investigation were to determine whether DCLF-induced
      nephrotoxicity involves oxidative stress and apoptotic type genomic DNA
      fragmentation, and if so, whether DCLF-induced oxidative stress and DNA
      fragmentation cause apoptotic cell death in mouse kidneys. Male ICR mice (CD-1;
      25-45 g), fed ad libitum, were administered nephrotoxic doses of DCLF (100, 200,
      300 mg/Kg, po) and sacrificed 24 h later. Blood was collected to evaluate renal
      injury (BUN), lipid peroxidation (MDA: malondialdehyde levels), and superoxide
      dismutase (SOD) activity (a marker of oxidative stress). Kidney tissues were
      analyzed both quantitatively and qualitatively to determine the degree and type
      of DNA damage, and evaluated histopathologically for the presence of apoptotic
      characteristics in the nucleus of diverse types of kidney cells. Results show
      that diclofenac is a powerful nephrotoxicant (at 100, 200, and 300 mg/kg: 4.7-,
      4.9-, and 5.0-fold increases in BUN compared to the control, respectively) and a
      strong inducer of oxidative stress (significant increase in MDA levels).
      Oxidative stress induced by DCLF was also coupled with massive kidney DNA
      fragmentation (100, 200, and 300 mg/kg: 3-, 8-, and 10-fold increases compared to
      control, respectively). A dose-dependent increase in MDA levels and SOD activity
      was also observed, which indicated a link between oxidative stress and
      nephrotoxicity. Qualitative analysis of DNA fragmentation by gel electrophoresis
      showed a DNA ladder indicative of Ca2+-Mg2+-endonuclease activation.
      Histopathological examination of kidney sections revealed numerous apoptotic
      nuclei across proximal and distal tubular cell linings. Collectively, these data
      for the first time suggest that DCLF-induced nephrotoxicity may involve
      production of reactive oxygen species leading to oxidative stress and massive
      genomic DNA fragmentation, and these two free radical mediated events may
      ultimately translate into apoptotic cell death of kidney cells in vivo, and
      reveal a DNA-active role for DCLF.

PMID- 11440827
TI  - Reduced sensitivity of inducible nitric oxide synthase-deficient mice to chronic
      colitis.
AB  - BACKGROUND: Overproduction of nitric oxide by the inducible form of nitric oxide
      synthase (iNOS) has been implicated in colitis. Different authors have postulated
      both toxic and protective effects of nitric oxide (NO) in the pathophysiology of
      active inflammation. The objective of this study was to examine the role of iNOS
      in experimental chronic colitis using iNOS-deficient mice. METHODS: For induction
      of colitis, mice received three cycles of 2% of dextran sodium sulfate (DSS)
      (M.W. 40,000) treatment in drinking water. The degree of colonic inflammation,
      leukocyte infiltration, and the expression of cell adhesion molecules were
      determined. INOS expression and nitrotyrosine were also determined by
      immunohistochemistry. RESULTS: After DSS treatment, a moderate colitis with
      marked cell infiltration was observed. Intense expression of iNOS was observed on
      infiltrating cells as well as on the colonic mucosal epithelium in these animals.
      In the iNOS-deficient mice, tissue damage was significantly diminished. No iNOS
      or nitrotyrosine staining was found in iNOS-deficient mice. The number of
      infiltrating cells and the expression of mucosal adressin cell adhesion molecule
      1 were significantly attenuated in the DSS-treated colon of iNOS-deficient mice.
      CONCLUSION: Induction of iNOS seems to act as a critical toxic effector molecule
      in the pathogenesis of chronic colonic inflammation.

PMID- 11440828
TI  - Estimation of lipid peroxidation of live cells using a fluorescent probe,
      diphenyl-1-pyrenylphosphine.
AB  - Diphenyl-1-pyrenylphosphine (DPPP), which reacts with lipid hydroperoxides
      stoichiometrically to yield fluorescent product DPPP oxide, was used as a
      fluorescent probe for lipid peroxidation in live cells. DPPP was successfully
      incorporated into U937 cells. Incorporation of DPPP into the cell membrane was
      confirmed by fluorescence microscopy. Reaction of DPPP with hydroperoxides was
      examined by monitoring increase in fluorescence intensity of the cell. It was
      found that lipid-soluble hydroperoxides such as methyl linoleate hydroperoxide
      preferably react with DPPP, whereas hydrogen peroxide did not react with DPPP
      located in the membrane. Linear correlation between increase in fluorescence
      intensity and the amount of methyl linoleate hydroperoxide applied to the cell
      was observed. DPPP gave little effect on cell proliferation, cell viability or
      cell morphology for at least 3 d. DPPP oxide, fluorescent product of DPPP, was
      quite stable in the membrane of living cells for at least 2 d. Fluorescence of
      DPPP-labeled cells was measured after treating with diethylmaleate (DEM), or 2,2'
      Azobis(2-amidinopropane) dihydrochloride (AAPH), or culturing with low serum
      content. These reagents and culture condition induced dose- and/or time-dependent
      increase in fluorescence. Addition of vitamin E effectively suppressed increase
      in fluorescence. When DPPP-labeled cells and DCFH-DA-labeled cells were treated
      with NO, H(2)O(2), AAPH, and DEM to compare the formation of hydoperoxides in the
      membrane and cytosol, distinct patterns of peroxide formation were observed.
      These results indicate that fluorescent probe DPPP is eligible for estimation of
      lipid peroxidation proceeding in the membrane of live cells, and use of this
      probe is especially advantageous in long-term peroxidation of the cell.

PMID- 11440829
TI  - Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)
      (carboxymethyl) lysine and hexitol-lysine.
AB  - Advanced glycation end products are a diverse class of posttranslational
      modifications, stemming from reactive aldehyde reactions, that have been
      implicated in the pathogenesis of a number of degenerative diseases. Because
      advanced glycation end products are accelerated by, and result in formation of,
      oxygen-derived free radicals, they represent an important component of the
      oxidative stress hypothesis of Alzheimer disease (AD). In this study, we used in
      situ techniques to assess N(epsilon)-(Carboxymethyl)lysine (CML), the predominant
      advanced glycation end product that accumulates in vivo, along with its glycation
      specific precursor hexitol-lysine, in patients with AD as well as in young and
      aged-matched control cases. Both CML and hexitol-lysine were increased in
      neurons, especially those containing intracellular neurofibrillary pathology in
      cases of AD. The increase in hexitol-lysine and CML in AD suggests that glycation
      is an early event in disease pathogenesis. In addition, because CML can result
      from either lipid peroxidation or advanced glycation, while hexitol-lysine is
      solely a product of glycation, this study, together with studies demonstrating
      the presence of 4-hydroxy-2-nonenal adducts and pentosidine, provides evidence of
      two distinct oxidative processes acting in concert in AD neuropathology. Our
      findings support the notion that aldehyde-mediated modifications, together with
      oxyradical-mediated modifications, are critical pathogenic factors in AD.

PMID- 11440830
TI  - Measurements of protein carbonyls, ortho- and meta-tyrosine and oxidative
      phosphorylation complex activity in mitochondria from young and old rats.
AB  - Mitochondrial bioenergetic function is often reported to decline with age and the
      accumulation of oxidative damage is thought to contribute. However, there are
      considerable uncertainties about the amount and significance of mitochondrial
      oxidative damage in aging. We hypothesized that, as radical production in
      mitochondria is greater than the rest of the cell, protein oxidative damage
      should accumulate more in mitochondria than the cytoplasm, and that this relative
      accumulation should increase with age. To test these hypotheses we measured the
      accumulation of three markers of protein oxidative damage in liver, brain, and
      heart from young and old rats. Ortho- and meta-tyrosine levels in protein
      hydrolysates were measured by a gas chromatography/mass spectrometry assay, and
      protein carbonyl content was determined by ELISA. Using these assays we found no
      evidence for increased protein oxidative damage in mitochondria relative to the
      cytosol. Most increases found in protein oxidative damage on aging were modest
      for all three tissues and there was no consistent pattern of increased oxidative
      damage in mitochondrial proteins on aging. Mitochondrial oxidative
      phosphorylation complex activities were also assessed revealing 39-42% decreases
      in F0F1--ATP synthase activity in liver and heart on aging, but not in other
      oxidative phosphorylation complexes. These findings have implications for the
      contribution of mitochondrial oxidative damage and dysfunction to aging.

PMID- 11440831
TI  - Dioxygen-dependent metabolism of nitric oxide in mammalian cells.
AB  - Steady-state gradients of NO within tissues and cells are controlled by rates of
      NO synthesis, diffusion, and decomposition. Mammalian cells and tissues actively
      decompose NO. Of several cell lines examined, the human colon CaCo-2 cell
      produces the most robust NO consumption activity. Cellular NO metabolism is
      mostly O2-dependent, produces near stoichiometric NO3-, and is inhibited by the
      heme poisons CN-, CO (K(I) approximately 3 microM), phenylhydrazine, and NO and
      the flavoenzyme inhibitor diphenylene iodonium. NO consumption is saturable by O2
      and NO and shows apparent K(M) values for O2 and NO of 17 and 0.2 microM,
      respectively. Mitochondrial respiration, O2*-, and H2O2 are neither sufficient
      nor necessary for O2-dependent NO metabolism by cells. The existence of an
      efficient mammalian heme and flavin-dependent NO dioxygenase is suggested. NO
      dioxygenation protects the NO-sensitive aconitases, cytochrome c oxidase, and
      cellular respiration from inhibition, and may serve a dual function in cells by
      limiting NO toxicity and by spatially coupling NO and O2 gradients.

PMID- 11440832
TI  - EGF receptor-ERK pathway is the major signaling pathway that mediates
      upregulation of aldose reductase expression under oxidative stress.
AB  - Acceleration of the polyol pathway and enhanced oxidative stress are implicated
      in the pathogenesis of diabetic complications. We and others recently reported
      that aldose reductase (AR), the rate-limiting enzyme in the polyol pathway, was
      upregulated by reactive oxygen and nitrogen species in vascular smooth muscle
      cells. To clarify the molecular mechanisms underlying these findings, we
      investigated the signal transduction pathways mediating AR expression using the
      rat vascular smooth muscle cell line A7r5. A selective epidermal growth factor
      (EGF) receptor kinase inhibitor, tyrphostin AG1478, significantly suppressed the
      hydrogen peroxide (H2O2)-induced increase in AR mRNA and enzyme activity.
      Activation of extracellular signal-regulated protein kinase (ERK) by H2O2 was
      blunted by AG1478. PD98059, a specific inhibitor of ERK kinase (MEK1), reduced
      H2O2-induced AR expression. EGF alone elicited activation of ERK and induction of
      AR expression. Increased level of AR transcript was demonstrated in cells treated
      with oxidized low-density lipoprotein, and this increase was also suppressed by
      AG1478. Inhibition of p38 MAP kinase by SB203580 also partially suppressed the
      H2O2-initiated AR induction. The presence of ponalrestat, an AR inhibitor,
      significantly accelerated H2O2-induced cell death. These results suggested that
      AR may act as a survival factor in these cells and that the EGF receptor-ERK
      pathway is the major signaling pathway involved in the upregulation of AR
      expression under oxidative stress.

PMID- 11440833
TI  - Lipofuscin-formation in retinal pigment epithelial cells is reduced by
      antioxidants.
AB  - The accumulation of lipofuscin by retinal pigment epithelium may be an important
      feature in the pathogenesis of age-related macular degeneration, suggesting the
      possibility that this common cause of blindness might be prevented or delayed by
      antioxidants. In support of this idea, we now report significantly reduced
      formation of lipofuscin when the antioxidant substances lutein, zeaxanthin,
      lycopene (carotenoids), or alpha-tocopherol were added to rabbit and bovine
      (calf) retinal pigment epithelial (RPE) cells exposed to normobaric hyperoxia
      (40%) and photoreceptor outer segments. Rabbit and calf RPE cells were grown for
      2 weeks with addition of one of the test substances every 48 h. The cellular
      uptake of carotenoids and alpha-tocopherol was assayed by HPLC after 2 weeks. The
      lipofuscin-content was measured by static fluorometry (rabbit cells) or by image
      analysis (calf cells). Both rabbit and calf RPE showed similar results with
      significantly lower amounts of lipofuscin in antioxidant-treated cells. The
      effect of carotenoids is especially interesting, since the result is not
      dependent on their protective effect against photo-oxidative reactions. The chain
      breaking abilities of these antioxidants in peroxidative reactions of lipid
      membranes and quenching of free radicals seem to be of importance for inhibition
      of lipofuscin formation.

PMID- 11440834
TI  - Tocopherols are metabolized in HepG2 cells by side chain omega-oxidation and
      consecutive beta-oxidation.
AB  - The metabolism of tocopherols by omega- and beta-oxidation of the phytyl side
      chain has been inferred from the identification of the final products
      carboxyethyl-hydroxychromans (CEHC) and immediate precursors, alpha- and gamma
      carboxymethylbutyl-hydroxychromans (CMBHCs). This hypothesis is here corroborated
      by the identification of a further alpha-tocopherol metabolite, alpha
      carboxymethylhexyl-hydroxychroman (alpha-CMHHC), and evidence for the involvement
      of a P450-type cytochrome. HepG2 cells, when exposed to 100 microM all-rac-alpha
      tocopherol, released alpha-CEHC, alpha-CMBHC, and alpha-CMHHC into the medium.
      The detection of those metabolites required pretreatment of the cells with alpha
      tocopherol for 10 d. In contrast, analogous metabolites of gamma and delta
      tocopherol were detectable without any preconditioning, while corresponding
      metabolites of RRR-alpha-tocopherol could not be detected at all. The formation
      of alpha-CEHC from all-rac-alpha-tocopherol was enhanced up to 5-fold by
      pretreatment of the HepG2 cells with rifampicin, known to induce CYP3A-type
      cytochromes with the capability of catalyzing omega-oxidation. In contrast,
      clofibrate did not reveal any effect. This observation suggests that a CYP3A-type
      cytochrome initiates tocopherol metabolism by omega-oxidation. It further reveals
      that inducible omega-oxidation is the rate-limiting step in tocopherol
      metabolism. It is discussed that competition of microsomal omega-oxidation with
      specific binding by the alpha-tocopherol transfer protein (alpha-TTP) determines
      the metabolic fate of the individual tocopherols.

PMID- 11440835
TI  - Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients.
AB  - The high incidence of cardiovascular disease in hemodialyzed (HD) patients is
      well established and oxidative stress has been involved in this phenomenon. The
      aim of our study was to evaluate if a vitamin E-coated dialyzer could offer
      protection to HD patients against oxidative stress. Sixteen HD patients were
      successively assessed for one month (i) on a high biocompatible synthetic
      dialyzer (AN) and (ii) on a vitamin E-coated dialyzer (VE). Blood samples were
      taken before and after the dialysis session at the end of each treatment period.
      HD session conducted with the AN dialyzer was responsible for acute oxidative
      stress, significantly assessed after HD by a decreased plasma vitamin C level and
      an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of
      oxidative stress. Plasma elastase activity, reflecting neutrophil activation, was
      also increased; soluble P-selectin, reflecting platelet activation, did not show
      any variation. The use of the VE dialyzer was associated with a less extended
      oxidative stress compared with the AN membrane: basal vitamin C level was higher,
      and after the HD session AFR/vitamin C ratio and elastase activity were not
      significantly increased. Plasma vitamin E levels were not affected. Our study
      demonstrates that HD is associated with oxidative stress, which can be partially
      prevented by the use of a vitamin E-coated dialyzer. Our data suggest that this
      dialyzer may exert a site-specific scavenging effect on free radical species in
      synergy with a reduced activation of neutrophils.

PMID- 11440836
TI  - Diaminonaphtalene, a new highly specific reagent for HPLC-UV measurement of total
      and free malondialdehyde in human plasma or serum.
AB  - We describe a new method to measure free and total malondialdehyde (MDA) in human
      plasma or serum, which is based on the derivatization of MDA with
      diaminonaphtalene (DAN) in an acidic medium at 37 degrees C. Derivatization is
      complete after 180 min at room temperature. By HPLC separation on a C18 column
      and diode array detection, the diazepinium thus formed exhibits a highly specific
      UV spectrum with a sharp maximum at 311 nm, which clearly distinguishes MDA from
      other short-chain aldehydes. Direct injection of deproteinized plasma avoids the
      use of an internal standard. The between-run imprecision is 9.1% (141 +/- 13 nM)
      for plasma and 6.6% (658 +/- 44 nM) for a commercial control. Typical within-day
      imprecision is 8% (93 +/- 7.5 nM) for total MDA, 3.2% (16 +/- 0.5 nM) for free
      MDA in plasma, and 1.6% (630 +/- 10 nM) for a commercial control. The recovery of
      MDA added to 10 different plasmas is 93-108% (mean = 100%). Plasma levels in
      healthy women (n = 79, 45-51 years) are 162 +/- 51 and 24 +/- 15 nM for total and
      free MDA, respectively. In younger men (n = 19, 21-37 years) total and free MDA
      are, respectively, 138 +/- 28 and 19 +/- 9 nM.

PMID- 11440837
TI  - Role of glutathione in regulation of hydroperoxidase I in growing Escherichia
      coli.
AB  - To examine role of glutathione in regulation of catalases in growing Escherichia
      coli, katG::lacZ and katE::lacZ fusions were transformed into a glutathione
      deficient Escherichia coli strain and wild-type parent. In the absence of H2O2
      and in the presence of the low H2O2 concentrations (0.1-3 mM), the gshA mutation
      stimulated katG::lacZ expression and the total catalase activity in exponential
      phase. In the absence of H2O2, the mutation in gshA also stimulated katE::lacZ
      expression. At higher H2O2 concentrations, the gshA mutation suppressed
      katG::lacZ expression and catalase activity. In stationary and mid-exponential
      phases, the intracellular concentrations of H2O2 in the gshA mutant were markedly
      increased compared to those in the wild type. These results suggest that
      glutathione may be involved in regulation of catalases.

PMID- 11440838
TI  - Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells.
AB  - Lipofuscin accumulates with age in a variety of highly metabolically active
      cells, including the retinal pigment epithelium (RPE) of the eye, where its
      photoreactivity has the potential for cellular damage. The aim of this study was
      to assess the phototoxic potential of lipofuscin in the retina. RPE cell cultures
      were fed isolated lipofuscin granules and maintained in basal medium for 7 d.
      Control cells lacking granules were cultured in an identical manner. Cultures
      were either maintained in the dark or exposed to visible light (2.8 mWcm2) at 37
      degrees C for up to 48 h. Cells were subsequently assessed for alterations in
      cell morphology, cell viability, lysosomal stability, lipid peroxidation, and
      protein oxidation. Exposure of lipofuscin-fed cells to short wavelength visible
      light (390-550 nm) caused lipid peroxidation (increased levels of malondialdehyde
      and 4-hydroxy-nonenal), protein oxidation (protein carbonyl formation), loss of
      lysosomal integrity, cytoplasmic vacuolation, and membrane blebbing culminating
      in cell death. This effect was wavelength-dependent because light exposure at 550
      to 800 nm had no adverse effect on lipofuscin-loaded cells. These results confirm
      the photoxicity of lipofuscin in a cellular system and implicate it in cell
      dysfunction such as occurs in ageing and retinal diseases.

PMID- 11440839
TI  - The antioxidant properties of zinc: interactions with iron and antioxidants.
AB  - Potential mechanisms underlying zinc's capacity to protect membranes from lipid
      oxidation were examined in liposomes. Using lipid oxidation initiators with
      different chemical and physical properties (transition metals, lipid- or water
      soluble azo compounds, ultraviolet radiation c (UVc), superoxide radical anion
      (O2*-), and peroxynitrite (ONOO-) we observed that zinc only prevented copper
      (Cu2+)- and iron (Fe2+)-initiated lipid oxidation. In the presence of Fe2+, the
      antioxidant action of zinc depended directly on the negative charge density of
      the membrane bilayer. An inverse correlation (r2: 0.96) was observed between the
      capacity of zinc to prevent iron binding to the membrane and the inhibitory
      effect of zinc on Fe2+-initiated lipid oxidation. The interaction of zinc with
      the bilayer did not affect physical properties of the membrane, including
      rigidification and lateral phase separation known to increase lipid oxidation
      rates. The interactions between zinc and the lipid- (alpha-tocopherol) and water-
      (epicatechin) soluble antioxidants were studied. The inhibition of Fe2+-induced
      lipid oxidation by either alpha-tocopherol or epicatechin was increased by the
      simultaneous addition of zinc. The combined actions of alpha-tocopherol (0.01
      mol%), epicatechin (0.5 microM) and zinc (5-50 microM) almost completely
      prevented Fe2+ (25 microM)-initiated lipid oxidation. These results show that
      zinc can protect membranes from iron-initiated lipid oxidation by occupying
      negatively charged sites with potential iron binding capacity. In addition, the
      synergistic actions of zinc with lipid and water-soluble antioxidants to prevent
      lipid oxidation, suggests that zinc is a pivotal component of the antioxidant
      defense network that protects membranes from oxidation.

PMID- 11440840
TI  - Chromatin silencing protein and pachytene checkpoint regulator Dot1p has a
      methyltransferase fold.
AB  - Although protein methylation has been observed for decades, its functional
      significance has remained largely unclear. Using sensitive profile searches and
      structural modeling, chromatin silencing protein and meiotic recombination
      checkpoint regulator Dot1p was identified as a putative protein
      methyltransferase. Along with recent results that link histone H3 methylation
      with chromatin silencing, this finding suggests that an expanded combinatorial
      repertoire of protein modifications affects transcriptional regulation.

PMID- 11440841
TI  - Longins: a new evolutionary conserved VAMP family sharing a novel SNARE domain.
AB  - This article describes the discovery of a novel SNARE domain that might be
      involved in the regulation of membrane fusion. This domain is shared by a novel
      family of VAMPs called long VAMPs or longins. Members of this family are more
      conserved among eukaryotes than are classical VAMPs, possibly because of their
      underlying basic SNARE function.

PMID- 11440852
TI  - Enzyme catalysis: a new definition accounting for noncovalent substrate- and
      product-like states.
AB  - Biological catalysis frequently causes changes in noncovalent bonding. By
      building on Pauling's assertion that any long-lived, chemically distinct
      interaction is a chemical bond, this article redefines enzyme catalysis as the
      facilitated making and/or breaking of chemical bonds, not just of covalent bonds.
      It is also argued that nearly every ATPase or GTPase is misnamed as a hydrolase
      and actually belongs to a distinct class of enzymes, termed here 'energases'. By
      transducing covalent bond energy into mechanical work, energases mediate such
      fundamental processes as protein folding, self-assembly, G-protein interactions,
      DNA replication, chromatin remodeling and even active transport.

PMID- 11440853
TI  - Insulin-degrading enzyme: embarking on amyloid destruction.
AB  - Several human disorders are caused by or associated with the deposition of
      protein aggregates known as amyloid fibrils. Despite the lack of sequence
      homology among amyloidogenic proteins, all amyloid fibrils share a common
      morphology, are insoluble under physiological conditions and are resistant to
      proteolytic degradation. Because amyloidogenic proteins are being produced
      continuously, eukaryotic organisms must have developed a form of proteolytic
      machinery capable of controlling these aggregation-prone species before their
      fibrillization. This article suggests that an intracellular metalloprotease
      called insulin-degrading enzyme (IDE) is responsible for the elimination of
      proteins with amyloidogenic potential and proposes a mechanism for the
      selectivity of the enzyme. In this respect, IDE can also be referred to as ADE:
      amyloid-degrading enzyme.

PMID- 11440854
TI  - Combinatorial control of protein phosphatase-1.
AB  - The catalytic subunit of the type 1 Ser/Thr protein phosphatases (PP1) can
      interact with many different regulatory (R) subunits. These R subunits function
      as activity-modulators, targeting subunits and/or substrates. The specificity of
      the R subunits can be accounted for by their interaction with specific subsets of
      binding pockets on the catalytic subunit and by the presence of subcellular
      targeting sequences. Hormones, growth factors and metabolites control the
      function of PP1 holoenzymes mainly by modulating the interaction of the subunits.

PMID- 11440855
TI  - Chromatin unfolding and activation by HMGN(*) chromosomal proteins.
AB  - The high mobility group N (HMGN) proteins are a family of nuclear proteins that
      binds to nucleosomes, changes the architecture of chromatin, and enhances
      transcription and replication from chromatin templates. The intracellular
      organization of the HMGN (previously known as HMG-14/17) proteins is dynamic and
      is related to both cell-cycle and transcriptional events. These proteins roam the
      nucleus, perhaps as part of multiprotein complexes, and their target interactions
      are modulated by posttranslational modifications. Functional studies on HMGN
      proteins provide insights into the molecular mechanisms by which structural
      proteins affect DNA-dependent activities in the context of chromatin.

PMID- 11440856
TI  - Single molecule nanobioscience.
AB  - In recent years, the rapid development and progress of single-molecule detection
      techniques have opened up a new era of biological research. The advantage of
      single-molecule studies is that data are not obscured by the ensemble-averaged
      measurements inherent in classical biochemical experiments. These techniques are
      shedding light on the dynamic and mechanistic properties of molecular machines,
      both in vivo and in vitro. This review summarizes the single-molecule experiments
      that have been designed to investigate molecular motors, enzyme reactions,
      protein dynamics, DNA transcription and cell signaling.

PMID- 11440857
TI  - Large scale domain movement in cytochrome bc(1): a new device for electron
      transfer in proteins.
AB  - Recently, crystallographic, spectroscopic, kinetic and biochemical genetic data
      have merged to unveil a large domain movement for the Fe-S subunit in cytochrome
      bc(1). In this evolutionarily conserved enzyme, the domain motion acts to conduct
      intra-complex electron transfer and is essential for redox energy conversion.

PMID- 11440858
TI  - Biochemistry and function of the DISC.

PMID- 11440859
TI  - From controlling elements to transposons: Barbara McClintock and the Nobel Prize.

PMID- 11440860
TI  - Kooyman symposium proceedings. A celebration of Jerry Kooyman's career and 65th
      year. April 14, 2000. La Jolla, California, USA.

PMID- 11440861
TI  - Field metabolic rate of lactating female Galapagos fur seals (Arctocephalus
      galapagoensis): the influence of offspring age and environment.
AB  - Galapagos fur seals, Arctocephalus galapagoensis, live in a seasonal environment
      which varies strongly in productivity from year to year. We measured how the
      field metabolic rates (FMR) of lactating females varied with season, pup age and
      year. Energy expenditure was measured using doubly labeled water (DLW) during the
      cold seasons of 1984 and 1985 in 9 mothers of 1-3-month-old pups and 5 mothers of
      yearlings, and during the 1986 warm season in 8 mothers of 6-month-old pups.
      Young pups gained 0.84% mass/day during the cold season, but larger pups during
      the warm season lost 1.25% mass/day. During the warm season, females had lower
      relative total body water than during the cold season suggesting higher fat
      content during the warm, less productive season, but the effect was even more
      marked when comparing different years of the study: fat content was high in 1984
      and 1986 and low in 1985. The FMR of mothers varied from 134 to 167 W but did not
      show significant differences between any of the pup age-groups. Among the years
      of the study, FMR showed only a trend towards low energy expenditure of mothers
      of young pups in 1984. The mean FMR was lower than for other otariids. Mothers
      may limit energy expenditure independent of pup age and season to minimize their
      own risk of starvation in an environment of comparatively low productivity,
      varying unpredictably due to frequent El Nino events.

PMID- 11440862
TI  - Adaptations to pressure in the RBC metabolism of diving mammals.
AB  - Marine mammals are known to dive up to 2000 m and, therefore, tolerate as much as
      200 atm. of hydrostatic pressure. To examine possible metabolic adaptations to
      these elevated pressures, fresh blood samples from marine and terrestrial mammals
      were incubated for 2 h at 37 degrees C under 136 atm (2000 psi) of hydrostatic
      pressure. The consumption of plasma glucose and the production of lactate over
      the 2-h period were used to assess glycolytic flux in the red cells. The results
      indicate that glycolytic flux as measured by lactate production under pressure
      can be significantly depressed in most terrestrial mammals and either not altered
      or accelerated in marine mammals. The data also suggest that there is a
      significant shift in the ratio of lactate produced to glucose consumed under
      pressure. Interestingly, human and dolphin blood do not react to pressure. These
      combined data imply a metabolic adaptation to pressure in marine mammal RBC that
      may not be necessary in human or dolphin cells due to their unique patterns of
      glucose metabolism.

PMID- 11440863
TI  - Three-dimensional movements and swimming activity of a northern elephant seal.
AB  - We attached a video system and data recorder to a northern elephant seal to track
      its three-dimensional movements and observe propulsive strokes of the hind
      flippers. During 6 h of recording, the seal made 20 dives and spent 90% of the
      time submerged. Average dive duration, maximum depth and swimming speed were 14.9
      min+/-6.1 S.D., 289 m+/-117 S.D. and 1.1 m s(-1)+/-0.12 S.D., respectively. The
      distance swum during a dive averaged 925 m+/-339 S.D., and the average descent
      and ascent angles were 41 degrees +/-18 S.D. and 50 degrees +/-21 S.D.,
      respectively. Dive paths were remarkably straight suggesting that the seal was
      navigating while submerged. We identified three modes of swimming based on the
      interval between propulsive strokes: continuous stroking; stroke-and-glide
      swimming; and prolonged gliding. The seal used continuous stroking from the
      surface to a mean depth of 20 m followed by stroke-and-glide swimming. Prolonged
      gliding started at a mean depth of 60 m and continued to the bottom of dives. For
      dives to depths of 300 m or more, 75% of the descent time was spent in prolonged
      gliding and 10% in stroke-and-glide swimming, amounting to 5.9-9.6 min of passive
      descent per dive. Average swimming speed varied little with swimming mode and was
      not a good indicator of propulsive effort. It appears that the seal can use
      prolonged gliding to reduce the cost of transport and increase dive duration.
      Energetically efficient locomotion may help explain the long and deep dives that
      routinely exceed the theoretical aerobic dive limit in this species.

PMID- 11440864
TI  - Aerobic dive limit: how often does it occur in nature?
AB  - Diving animals offer a unique opportunity to study the importance of
      physiological constraint in their everyday behaviors. An important component of
      the physiological capability of any diving animal is its aerobic dive limit
      (ADL). The ADL has only been measured in a few species. The goal of this study
      was to estimate the aerobic dive limit from measurements of body oxygen stores
      and at sea metabolism. This calculated ADL (cADL) was then compared to
      measurements of diving behavior of individual animals of three species of
      otariids, the Antarctic fur seal, Arctocephalus gazella, the Australian sea lion,
      Neophoca cinerea, and the New Zealand sea lion, Phocarctos hookeri. Antarctic fur
      seals dove well within the cADL. In contrast, many individuals of both sea lion
      species exceeded the cADL, some by significant amounts. Australian sea lions
      typically dove 1.4 times longer than the cADL, while New Zealand sea lions on
      average dove 1.5 times longer than the cADL. The tendency to exceed the cADL was
      correlated with the dive pattern of individual animals. In both Antarctic Fur
      Seals and Australian sea lions, deeper diving females made longer dives that
      approached or exceeded the cADL (P<0.01, r(2)=0.54). Australian and New Zealand
      sea lions with longer bottom times also exceeded the cADL to a greater degree.
      The two sea lions forage on the benthos while the fur seals feed shallow in the
      water column. It appears that benthic foraging requires these animals to reach or
      exceed their aerobic dive limit.

PMID- 11440865
TI  - A killer appetite: metabolic consequences of carnivory in marine mammals.
AB  - Among terrestrial mammals, the morphology of the gastrointestinal tract reflects
      the metabolic demands of the animal and individual requirements for processing,
      distributing, and absorbing nutrients. To determine if gastrointestinal tract
      morphology is similarly correlated with metabolic requirements in marine mammals,
      we examined the relationship between basal metabolic rate (BMR) and small
      intestinal length in pinnipeds and cetaceans. Oxygen consumption was measured for
      resting bottlenose dolphins and Weddell seals, and the results combined with data
      for four additional species of carnivorous marine mammal. Data for small
      intestinal length were obtained from previously published reports. Similar
      analyses were conducted for five species of carnivorous terrestrial mammal, for
      which BMR and intestinal length were known. The results indicate that the BMRs of
      Weddell seals and dolphins resting on the water surface are 1.6 and 2.3 times the
      predicted levels for similarly sized domestic terrestrial mammals, respectively.
      Small intestinal lengths for carnivorous marine mammals depend on body size and
      are comparatively longer than those of terrestrial carnivores. The relationship
      between basal metabolic rate (kcal day(-1)) and small intestinal length (m) for
      both marine and terrestrial carnivores was, BMR=142.5 intestinal length(1.20)
      (r(2)=0.83). We suggest that elevated metabolic rates among marine mammal
      carnivores are associated with comparatively large alimentary tracts that are
      presumably required for supporting the energetic demands of an aquatic lifestyle
      and for feeding on vertebrate and invertebrate prey.

PMID- 11440866
TI  - The diving behavior of blue and fin whales: is dive duration shorter than
      expected based on oxygen stores?
AB  - Many diving seabirds and marine mammals have been found to regularly exceed their
      theoretical aerobic dive limit (TADL). No animals have been found to dive for
      durations that are consistently shorter than their TADL. We attached time-depth
      recorders to 7 blue whales and 15 fin whales (family Balaenopteridae). The diving
      behavior of both species was similar, and we distinguished between foraging and
      traveling dives. Foraging dives in both species were deeper, longer in duration
      and distinguished by a series of vertical excursions where lunge feeding
      presumably occurred. Foraging blue whales lunged 2.4 (+/-1.13) times per dive,
      with a maximum of six times and average vertical excursion of 30.2 (+/-10.04) m.
      Foraging fin whales lunged 1.7 (+/-0.88) times per dive, with a maximum of eight
      times and average vertical excursion of 21.2 (+/-4.35) m. The maximum rate of
      ascent of lunges was higher than the maximum rate of descent in both species,
      indicating that feeding lunges occurred on ascent. Foraging dives were deeper and
      longer than non-feeding dives in both species. On average, blue whales dived to
      140.0 (+/-46.01) m and 7.8 (+/-1.89) min when foraging, and 67.6 (+/-51.46) m and
      4.9 (+/-2.53) min when not foraging. Fin whales dived to 97.9 (+/-32.59) m and
      6.3 (+/-1.53) min when foraging and to 59.3 (+/-29.67) m and 4.2 (+/-1.67) min
      when not foraging. The longest dives recorded for both species, 14.7 min for blue
      whales and 16.9 min for fin whales, were considerably shorter than the TADL of
      31.2 and 28.6 min, respectively. An allometric comparison of seven families
      diving to an average depth of 80-150 m showed a significant relationship between
      body mass and dive duration once Balaenopteridae whales, with a mean dive
      duration of 6.8 min, were excluded from the analysis. Thus, the short dive
      durations of blue whales and fin whales cannot be explained by the shallow
      distribution of their prey. We propose instead that short duration diving in
      large whales results from either: (1) dispersal behavior of prey; or (2) a high
      energetic cost of foraging.

PMID- 11440867
TI  - Temperature regulation in emperor penguins foraging under sea ice.
AB  - Inferior vena caval (IVC) and anterior abdominal (AA) temperatures were recorded
      in seven emperor penguins (Aptenodytes forsteri) foraging under sea ice in order
      to evaluate the hypothesis that hypothermia-induced metabolic suppression might
      extend aerobic diving time. Diving durations ranged from 1 to 12.5 min, with 39%
      of dives greater than the measured aerobic dive limit of 5.6 min. Anterior
      abdominal temperature decreased progressively throughout dives, and partially
      returned to pre-dive values during surface intervals. The lowest AA temperature
      was 19 degrees C. However, mean AA temperatures during dives did not correlate
      with diving durations. In six of seven penguins, only minor fluctuations in IVC
      temperatures occurred during diving. These changes were often elevations in
      temperature. In the one exception, although IVC temperatures decreased, the
      reductions were less than those in the anterior abdomen and did not correlate
      with diving durations. Because of these findings, we consider it unlikely that
      regional hypothermia in emperor penguins leads to a significant reduction in
      oxygen consumption of the major organs within the abdominal core. Rather,
      temperature profiles during dives are consistent with a model of regional
      heterothermy with conservation of core temperature, peripheral vasoconstriction,
      and cooling of an outer body shell.

PMID- 11440868
TI  - Re-evaluation of the allometry of wet thermal conductance for birds.
AB  - Wet thermal conductance is an important thermoregulatory parameter for birds and
      mammals. It is generally calculated as C(wet) (ml O2 g(-1) h(-1) degrees C(-1)) =
      VO2/(T(b)-T(a)), where VO2 is metabolic rate measured in ml O2 g(-1) h(-1), T(b)
      is body and T(a) is ambient temperature measured in degrees C. Minimum C(wet) is
      measured at T(a) at or below the lower critical temperature (T(lc)) of the
      thermoneutral zone, and is strongly influenced by time of day (rest or activity
      phase) and body mass [J. Aschoff, Comp. Biochem. Physiol. 69A (1981) 611].
      Allometric analyses indicate differences in C(wet) for passerine and non
      passerine birds, in their rest and active phases (Aschoff, 1981). The allometric
      slope for non-passerine rest-phase (-0.583) is lower than that for non-passerine
      active-phase (-0.484), and passerine rest-phase (-0.461) and active-phase (
      0.463), although none of these slopes are significantly different. This different
      sloped relationship for non-passerine rest-phase C(wet) extrapolates to lower
      than-expected values at high body mass, and so this allometric relationship may
      be inappropriate for predictive purposes. Consequently, we have reanalysed
      Aschoff's (1981) data, as well as more recent compilations, to determine a more
      useful allometric relationship for C(wet) of non-passerine rest-phase birds. Re
      analyses of minimum thermal conductance data from Drent and Stonehouse [Comp.
      Biochem. Physiol. 40A (1971) 689], Aschoff (1981) and Gavrilov and Dolnik [Acta
      XVIII Congressus Internationalis Ornithologici Moscow (1982) 421] indicate that
      the most appropriate regressions for predicting C(wet) (ml O2 g(-1) h(-1) degrees
      C(-1)) of birds from body mass (M; g) are the pooled regressions for non
      passerine and passerine birds, in the active (alpha) and resting (rho) phases,
      using data tabulated by Aschoff (1981): alpha, C(wet)=0.994M(-0.509); rho,
      C(wet)=0.702M(-0.519). C(wet) is approximately 40% higher in the active phase
      than the rest phase. Regressions of various data sets for C(wet) of birds and
      mammals indicate a similar slope of approximately -0.5 for the allometric
      relationship, but significantly higher elevations for mammals compared to birds.
      The approximately 50% higher C(wet) for mammals than birds indicates a better
      physical insulation for birds than mammals of the same body mass. The general
      scaling of C(wet) with M(-0.5) indicates that (T(b)-T(lc)) should scale with
      M(0.22), if mass-specific metabolic rate scales with M(-0.28) [Reynolds and Lee,
      Am. Nat. 147 (1996) 735]. The observed scaling for (T(b)-T(lc)) of M(0.183)
      (calculated from Gavrilov and Dolnik, 1985) is consistent with this expectation.

PMID- 11440869
TI  - Fasting metabolism in Antarctic fur seal (Arctocephalus gazella) pups.
AB  - The metabolism of 52-73-day old Antarctic fur seal pups from Bird Island, South
      Georgia, was investigated during fasting periods of normal duration while their
      mothers were at sea foraging. Body mass decreased exponentially with pups losing
      3.5-3.8% of body mass per day. Resting metabolic rate also decreased
      exponentially from 172-197 ml (O2) x min(-1) at the beginning of the fast and
      scaled to M(b)(0.74) at 2.3 times the level predicted for adult terrestrial
      mammals of similar size. While there was no significant sex difference in RMR,
      female pups had significantly higher (F(1,18)=6.614, P<0.019) mass-specific RMR
      than male pups throughout the fasting period. Fasting FMR was also significantly
      (t(15)=2.37, P<0.035) greater in females (823 kJ x kg(-1) x d(-1)) than males
      (686 kJ x kg(-1) x d(-1)). Average protein turnover during the study period was
      19.3 g x d(-1) and contributed to 5.4% of total energy expenditure, indicating
      the adoption of a protein-sparing strategy with a reliance on primarily lipid
      catabolism for metabolic energy. This is supported by observed decreases in
      plasma BUN, U/C, glucose and triglyceride concentrations, and an increase in beta
      HBA concentration, indicating that Antarctic fur seals pups adopt this strategy
      within 2-3 days of fasting. Mean RQ also decreased from 0.77 to 0.72 within 3
      days of fasting, further supporting a rapid commencement of protein-sparing.
      However, RQ gradually increased thereafter to 0.77, suggesting a resumption of
      protein catabolism which was not substantiated by changes in plasma metabolites.
      Female pups had higher TBL (%) than males for any given mass, which is consistent
      with previous findings in this and other fur seal species, and suggests sex
      differences in metabolic fuel use. The observed changes in plasma metabolites and
      protein turnover, however, do not support this.

PMID- 11440870
TI  - cAMP and sodium transport in the freshwater crayfish, Cherax destructor.
AB  - Crayfish in which sodium absorption was maximally stimulated had elevated levels
      of both cAMP and Na(+)-K(+)-ATPase activity in gill tissue. The concentration of
      cAMP and activity of Na(+)-K(+)-ATPase in gill tissue were monitored following
      transfer of crayfish from water containing 125 mmol x l(-1) Na to Na-free media.
      Both parameters were significantly elevated within 10 min of transfer to Na-free
      media and [cAMP] peaked between 1 and 2 h before falling transiently to the
      control level at 3 h. A second peak of [cAMP] and a further rise in Na(+)-K(+)
      ATPase activity were evident 6 h after transfer and elevated levels were then
      maintained. The pattern observed was consistent with the existence of two
      separate mechanisms for the control of sodium absorption both of which stimulated
      the activity of Na(+)-K(+)-ATPase via elevation of the intracellular
      concentration of cAMP. The initial response was very rapid (<10 min) but of brief
      duration (1-2 h) and this mechanism appeared to be sensitive to changes in
      external ion levels. The second mechanism exhibited a much longer response time
      (3-6 h) and duration and was likely to be sensitive to changes in internal ion
      concentrations.

PMID- 11440871
TI  - Secretion of whey acidic protein and cystatin is down regulated at mid-lactation
      in the red kangaroo (Macropus rufus).
AB  - Milk collected from the red kangaroo (Macropus rufus) between day 100 and 260 of
      lactation showed major changes in milk composition at around day 200 of
      lactation, the time at which the pouch young begins to temporarily exit the pouch
      and eat herbage. The carbohydrate content of milk declined abruptly at this time
      and although there was only a small increase in total protein content, SDS PAGE
      analysis of milk revealed asynchrony in the secretory pattern of individual
      proteins. The levels of alpha-lactalbumin, beta-lactoglobulin, serum albumin and
      transferrin remain unchanged during lactation. In contrast, the protease
      inhibitor cystatin, and the putative protease inhibitor whey acidic protein (WAP)
      first appeared in milk at elevated concentrations after approximately 150 days of
      lactation and then ceased to be secreted at approximately 200 days. In addition,
      a major whey protein, late lactation protein, was first detected in milk around
      the time whey acidic protein and cystatin cease to be secreted and was present at
      least until day 260 of lactation. The co-ordinated, but asynchronous secretion of
      putative protease inhibitors in milk may have several roles during lactation
      including tissue remodelling in the mammary gland and protecting specific
      proteins in milk required for physiological development of the dependent young.

PMID- 11440872
TI  - Do circulating plasma AVT and/or cortisol levels control pulsatile urea excretion
      in the gulf toadfish (Opsanus beta)?
AB  - Previous work has shown that pulsatile urea excretion at the gills of the gulf
      toadfish is due to periodic activation of a facilitated diffusion transport
      system with molecular and pharmacological similarity to the UT-A transport system
      of the mammalian kidney. In mammals, AVP and glucocorticoids are two important
      endocrine regulators of this system. The present study focused on the potential
      role of circulating AVT (the teleost homologue of AVP) and cortisol levels as
      possible triggers for urea pulses. Long-term (34-84 h) monitoring of plasma
      levels by repetitive sampling at 2-h intervals from chronic cannulae in
      individual toadfish demonstrated that circulating AVT concentrations are low (10(
      12)-10(-11) M), and show no relationship to the occurrence of natural urea
      pulses. In contrast, plasma cortisol levels decline greatly prior to natural
      pulses and rise rapidly thereafter. AVT injections into the caudal artery or
      ventral aorta elicited pulse events, but these were extremely small (1-10%)
      relative to natural pulses, and occurred only at unphysiological dose levels (10(
      9) M in the plasma). AVP was a partial agonist, but isotocin, insulin-like growth
      factor-1, and atrial natriuretic peptide were without effect at the same
      concentration. Artificially raising plasma cortisol levels by cortisol injection
      tended to reduce responsiveness to AVT. Pharmacological reduction of plasma
      cortisol levels by metyrapone injection elicited small pulses similar to those
      caused by AVT. Following such pulse events, AVT was ineffective in inducing
      pulses. We conclude that decreases in circulating cortisol play an important
      permissive role in urea pulsing, but that circulating AVT levels are not
      involved.

PMID- 11440873
TI  - Osmoregulation in Onymacris rugatipennis, a free-ranging tenebrionid beetle from
      the Namib Desert.
AB  - Haemolymph levels of organic and inorganic constituents were investigated in the
      tenebrionid Onymacris rugatipennis during dehydration and rehydration. The major
      osmolar effectors are sodium (26%), chloride (24%), amino acids (18%), and sugars
      (11%); regulation of haemolymph osmotic pressure (OP) during dehydration is
      effected largely by a reduction in the haemolymph content of these constituents.
      Changes in amino acid levels are not the result of interchanges with soluble
      protein. During rehydration, the main contributors to osmoregulation are sodium
      (26%), chloride (24%), and an increase in haemolymph solute(s) not measured in
      this study (31%). Of the sodium removed from the haemolymph during dehydration,
      21.2% was excreted. Faecal losses of potassium during dehydration far exceeded
      the amounts removed from the haemolymph; however, haemolymph potassium levels
      were strongly regulated during rehydration. Regulatory efficiency increases as
      desiccation proceeds, and is greatest only when this species is severely
      challenged.

PMID- 11440874
TI  - Concentrations of insulin-like growth factor-I in adult male white-tailed deer
      (Odocoileus virginianus): associations with serum testosterone, morphometrics and
      age during and after the breeding season.
AB  - Our understanding of insulin-like growth factor-I (IGF-I) in cervids has been
      limited mostly to its effects on antler development in red deer (Cervus elaphus),
      roe deer (Capreolus capreolus), fallow deer (Dama dama), and pudu (Pudu puda).
      Although IGF-I has been found to play a critical role in reproductive function of
      other mammals, its role in reproduction of deer is unknown. The objectives of the
      present study were to determine if serum levels of IGF-I change during the
      breeding season, assess whether age influences serum IGF-I, compare levels of IGF
      I measured during and following the breeding season, and determine if IGF-I is
      associated with body and antler characteristics in free-ranging adult, male white
      tailed deer (Odocoileus virginianus). We collected serum and morphometric data
      from hunter-harvested and captured white-tailed deer to investigate these
      objectives. Mean level of serum IGF-I during the breeding season was 63.6 ng/ml
      and was greatest in deer between 2.5 and 5.5 years old (57.4-79.9 ng/ml). Levels
      of serum IGF-I decreased by approximately 40% as the breeding season progressed,
      but levels were less in deer following the breeding season (34.6 ng/ml). Both
      body and antler size were associated positively with IGF-I when controlling for
      age. Serum testosterone was also associated positively with IGF-I. Levels of
      serum testosterone during the breeding season generally increased with age from
      4.82 (1.5 years old) to 18.79 ng/dl (5.5 years old), but decreased thereafter.
      These data suggest that IGF-I may be an important hormone in breeding, male white
      tailed deer.

PMID- 11440875
TI  - Thyroxine and vitamin D in the gorgonian Leptogorgia virgulata.
AB  - The gorgonian coral Leptogorgia virgulata contains thyroxine, or a thyroxine-like
      substance, referred to here as G-T(4). The G-T(4) levels were significantly
      higher in colonies collected in the summer vs. winter months. Using
      immunocytochemical techniques, G-T(4) was localized in the axis, polyp
      epithelium, and within the electron dense bodies of scleroblasts (spicule-forming
      cells), as well as on the periphery of spicules. G-T(4) was also localized in the
      mesoglea between closely adjacent scleroblasts. The effects of exogenous T(4) on
      the uptake of Ca(45) was determined in spicule, tissue and axis fractions of L.
      virgulata. The uptake of Ca(45) increased in T(4) treated spicules but decreased
      in the tissue fraction for all time periods tested. The uptake of Ca(45) into
      axes was not affected by exogenous T(4) until day 10 of the study. These data
      suggest that G-T(4) may function in the process of spicule formation. 1,25
      dihydroxyvitamin D apparently is synthesized via ultraviolet radiation. Colonies
      deprived of ultraviolet radiation had significantly more 'irregular' spicules
      than colonies maintained in ultraviolet radiation. Exposure to sunlight therefore
      may be associated with the process of normal spicule formation.

PMID- 11440876
TI  - Hepatopancreas is the extraovarian site of vitellogenin synthesis in black tiger
      shrimp, Penaeus monodon.
AB  - The site of yolk protein synthesis in crustaceans has long been a subject of
      controversy. The vitellogenin gene structure was partially reported only very
      recently in Macrobrachium rosenbergii, after which the hepatopancreas was
      confirmed as the extraovarian site of vitellogenin synthesis in that species.
      Ovaries are the most frequently reported as the site of yolk protein synthesis in
      penaeid shrimp. Using cDNA reversed-transcribed from mRNA isolated from the
      hepatopancreas of vitellogenic female shrimp, Penaeus monodon, we found that its
      deduced amino acid sequence had high identity of 48% with that from M.
      rosenbergii vitellogenin. A similar location of the intron in the sequenced
      region of genomic DNA was also found between these two species. We therefore
      concluded that the hepatopancreas the extraovarian site of vitellogenin synthesis
      in P. monodon in vivo. The partial structure of vitellogenin gene is presented in
      this study.

PMID- 11440877
TI  - Energetics and litter size variation in domestic dog Canis familiaris breeds of
      two sizes.
AB  - We measured resting metabolic rate (RMR), daily energy expenditure (DEE) and
      metabolisable energy intake (MEI) in two breeds of dog during peak lactation to
      test whether litter size differences were a likely consequence of allometric
      variation in energetics. RMR of Labrador retrievers (30 kg, n=12) and miniature
      Schnauzers (6 kg, n=4) averaged 3437 and 1062 kJ/day, respectively. DEE of
      Labradors (n=6) and Schnauzers (n=4) averaged 9808 and 2619 kJ/day, respectively.
      MEI of Labradors (n=12) was 22448 kJ/day and of Schnauzers (n=7) was 5382 kJ/day.
      DEE of Labrador pups (2.13 kg, n=19) was 974 kJ/day and Schnauzers (0.89 kg, n=7)
      were 490 kJ/day. Although Labradors had higher MEIs than Schnauzers during peak
      lactation, there was no difference in mass-specific energy expenditure between
      the two breeds. Hence, it is unlikely that litter size variation is a likely
      consequence of differences in maternal energy expenditure. Individual offspring
      were relatively more costly for mothers of the smaller breed to produce.
      Therefore, litter size variations were consistent with the expectation that
      smaller offspring should be more costly for mothers, but not that smaller mothers
      should per se invest more resources in reproduction.

PMID- 11440878
TI  - Restoration of the jejunal mucosa in rats refed after prolonged fasting.
AB  - To investigate the importance of body fuel depletion on gut rehabilitation after
      food deprivation, we compared the kinetics of jejunal mucosa alteration and
      restoration in rats that were refed after reaching different stages in body fuel
      depletion. Rats (P2) were refed while still in the so-called phase II, where body
      protein utilization is minimized, whereas rats (P3) were refed when they had
      reached the stage of increasing protein utilization (phase III). There was a
      significant decrease in total mass of intestine (P2, -30%; P3, -40%) and jejunal
      mucosa (P2, -52%; P3, -60%), as well in the size of the crypts (P2, -15%; P3, 
      36%) and villi (P2, -37%; P3, -55%). Structural changes of the mucosa included
      disappearance of some villi and a reduction in the size and number of crypts.
      Despite the larger morphological alterations in P3, the restoration of mucosa was
      as fast and complete after only 3 days of refeeding for both P2 and P3 rats. The
      respective roles of the mitosis pressure and of the lamina propria dynamics were
      studied. The rapid reversibility of the gut mucosal alterations due to fasting
      might constitute an integrative process.

PMID- 11440879
TI  - Cold adaptive thermogenesis in small mammals from different geographical zones of
      China.
AB  - The mechanisms of thermogenesis and thermoregulation were studied in the tree
      shrew (Tupaia belangeri) and greater vole (Eothenomys miletus) of the subtropical
      region, and Brandt's vole (Microtus brandti), Mongolian gerbil (Meriones
      unguiculatus), Daurian ground squirrel (Spermophilus dauricus) and plateau pika
      (Ochotona curzoniae) of the northern temperate zone. Resting metabolic rate (RMR)
      and non-shivering thermogenesis (NST) increased significantly in T. belangeri, E.
      miletus, M. brandti and M. unguiculatus after cold acclimation (4 degrees C) for
      4 weeks. In T. belangeri, the increase in RMR and thermogenesis at liver cellular
      level were responsible for enhancing the capacity of enduring cold stress, and
      homeothermia was simultaneously extended. Stable body temperature in M. brandti,
      E. miletus, M. unguiculatus and O. curzoniae was maintained mainly through
      increase in NST, brown adipose tissue (BAT) mass and its mitochondrial protein
      content, and the upregulation of uncoupling protein (UCP1) mRNA, as well as
      enhancement of the activity of cytochrome C oxidase, alpha-glycerophosphate
      oxidase and T(4) 5'-deiodinase in BAT mitochondria. The RMR in O. curzoniae and
      euthermic S. dauricus was not changed, while NST significantly increased during
      cold exposure; the former maintained their stable body temperature and mass,
      while body temperature in the latter declined by 4.8 degrees C. The serum T(3)
      concentration or ratio of T(3)/T(4) in all the species was enhanced after cold
      acclimation. Results indicated that: (1) the adaptive mechanisms of T. belangeri
      residing in the subtropical region to cold are primarily by increasing RMR and
      secondly by increasing NST, and the mechanisms of thermogenesis are similar to
      those in tropical mammals; (2) in small mammals residing in northern regions, the
      adaptation to cold is chiefly to increase NST; (3) the mechanism of cold-induced
      thermogenesis in E. miletus residing in subtropical and high mountain regions is
      similar to that in the north; (4) a low RMR in warm environments and peak RMR and
      NST in cold environments enabled M. unguiculatus to tolerate a semi-desert
      climate; (5) O. curzoniae has unusually high RMR and high NST, acting mainly via
      increasing NST to adapt to extreme cold of the Qinghai-Tibet Plateau; (6) the
      adaptation of euthermic S. dauricus to cold is due to an increase in NST and a
      relaxed homeothermia; and lastly (7) the thyroid hormone is involved in the
      regulation of cold adaptive thermogenesis in all the species studied.

PMID- 11440880
TI  - [Cholera in Tamatave (Madagascar) February-July 2000: epidemiological
      characteristics].
AB  - The seventh pandemic of cholera reached Madagascar in March 1999. In 15 months of
      dissemination, 31,095 people were infected, 5.8% of whom died. The first case in
      Madagascar was recorded in Tamatave (the second largest city and the island's
      main port, on the east coast) on February 29 2000. The health services of the
      district responded efficiently to the crisis. We carried out an epidemiological
      investigation to determine the characteristics of the outbreak in Tamatave. We
      retrospectively studied the records of patients consulting for diarrhea at the
      health centers of Tamatave from February 29 to June 30 2000. We defined cholera
      cases according to the recommendations of the World Health Organization for
      international notification. We recorded the date of diagnosis, sex, age, address,
      main clinical symptoms, treatment and outcome. Statistical analysis was carried
      out with Epi Infor 5.01b software. During the 123 days of the study, we recorded
      356 cases of cholera, 5 of whom died (attack rate = 2.5 per thousand, case
      fatality rate = 1.4%). The median age of the patients was 27 years and 8 months
      and the sex ratio was 1. The attack rate was highest for men aged over 50 years.
      Severe clinical signs were observed in one sixth of the cases. Men aged 15 to 29
      years and 30 to 49 years presented more severe disease than women of the same age
      (relative rates of 3.6 and 5.9 respectively, p < 0.01). Cholera may become
      endemic in this province following this outbreak. It may be difficult to stop the
      spread of cholera within a country but appropriate organization of the medical
      structure and staff and training in cholera management may decrease the rate of
      mortality due to this disease.

PMID- 11440881
TI  - [Evaluation of bacterial and polluting loads of effluent from activated sludge
      wastewater treatment plants in Yaounde, Cameroon].
AB  - Activated sludge wastewater treatment plants in Yaounde are plagued by failures
      in their operation. A microbiological and physico-chemical study was carried out
      on wastewater effluent of an hospital, university campus, and two residential
      areas made up of more than 2,000 apartments connected to two collective sewase
      systems. Wastewater sampling was performed in the form of daily cycles during
      which composite samples were made every two hours with samples collected every
      half hour. Variables measured included incoming flow rates, suspended solids, pH,
      electrical conductivity, ammonia nitrogen, total Kjeldahl nitrogen (combination
      of ammonia and organic nitrogen) and total reactive phosphorus, BOD5 and COD.
      Microorganisms were isolated on selective culture media using membrane filter
      procedures. The results obtained show that effluent discharged in receiving
      waters are, in general, not treated. The suspended solids contents of raw sewage
      range from 120 to 2,600 mg/l. In General Hospital a mean value of suspended
      solids of 31.8 mg/l was obtained for treated wastewater. pH values of both raw
      and treated sewage range from 6 to 8.5 units. Mean values of the conductivity of
      treated and raw wastewater range from 449.7 to 1,038.3 microseconds/cm. The TKN
      contents of untreated wastewater are comprised between 36 and 259.2 mg/l. These
      values range from 5 to 20 mg/l for treated effluent in the General Hospital
      plant. Large amounts of total hydrolysable phosphorus varying from 3.8 to 27.9
      mg/l are present in wastewater from the plants. Influent BOD5 of Grand Messa,
      Cite Verte and university campus wastewater range from 110 to 530 mgO2/l. Values
      recorded indicate an important input of organic matter to receiving waters. In
      the case of biotic components, test germs densities registered in the influent of
      Grand Messa and those of Cite Verte are comprised between 9 x 106 and 88 x 107
      CFU/100 ml for fecal coliforms, and between 9 x 105 and 74 x 107 CFU/100 ml for
      fecal streptococci. The densities of Aeromonas hydrophila in Grand Messa and Cite
      Verte influent fluctuate between 30 x 106 and 65 x 108 CFU/100 ml. Influent of
      university campus harbour 10 x 105. Densities of Pseudomonas aeruginosa remain
      below 70 x 105 CFU/100 ml. Treated effluent BOD5 values range from 48 to 150
      mgO2/l. Such values indicate an inefficient treatment. The decrease in bacterial
      densities is limited to 2 logarithmic units. Treated effluent still harbour 10 x
      103 to 10 x 105 CFU/100 ml for fecal coliforms, and 20 x 102 to 12 x 104 CFU/100
      ml for fecal streptococci. These values range from 10 x 104 to 50 x 105 CFU/100
      ml for Aeromonas hydrophila. Pseudomonas aeruginosa densities remain in general
      below 40 x 104 CFU/100 ml. Discharges from these wastewater treatment plants are
      responsible for the permanent fecal contamination of the environment and a lack
      of proper hygiene. Furthermore, they produce overfertilization of receiving
      waters.

PMID- 11440882
TI  - [How is breast-feeding valued in the urban and semi-urban Central African
      milieu?].
AB  - Efforts have been made for several years to promote the use of breast milk by
      mothers. This is important for mothers in developing countries faced with
      economic problems, especially for those tempted by milk substitutes. Fortunately,
      BF (breast feeding) is used by a majority of women in these developing countries,
      its practice is often influenced by an early introduction of supplements. Why
      this early supplementation? In order to answer this question we performed this
      study, a transversal survey of mothers in neonatal period in a regional town and
      the capital of Central Africa. The compilation of data of this seven month study,
      carried out in four maternities and nine SMI centers, was carried out from a pre
      established questionnaire. This allowed us to obtain the following results. We
      interrogated 734 mothers of newborn babies aged between 14 and 45 years,
      including 534 in Bangui and 200 in Bossangoa. Breast feeding was chosen by 96.5%
      of mothers, however exclusive breast feeding was only carried out by 17% of
      mothers. Feeding on demand was widely spread both in Bangui (92.7%) and in
      Bossangoa (92%). Breast milk was the first food received at birth by 84.5% of
      newborn babies. At the neonatal period, water supplementation was more frequent
      (78.1%, including 23% at birth) than that of solid or semi-liquid food (6.2%).
      The value given to breast milk was just nutritional, its other virtues were not
      well known. Conclusion, In breast mil remains the food of choice in our country.
      However, its practice suffers from much ignorance. An effort should be made to
      heighten awareness and give milk its due worth.

PMID- 11440883
TI  - [Prognosis of twin deliveries in an African milieu].
AB  - We carried out a retrospective study of 101 multiple pregnancies between January
      1st 1997 and June 30 1999, to investigate the prognosis of twin deliveries at the
      Josephine Bongo Maternity Unit. The frequency of twin deliveries was 2.22%,
      corresponding to over 1 in 45 deliveries. Mean birth weight was 2,309.6 +/-
      369.31 g for the first twin and 2,234.31 +/- 397.58 g for the second twin. The
      frequency of cesarean section was 11% for the first twin and 18% for the second
      twin. The neonatal mortality rate was 30 per thousand for the first twin and 50
      per thousand for the second twin. The reorganization of mother and child health
      services would help to improve fetal prognosis in twin deliveries.

PMID- 11440884
TI  - [The value of occupational health in the national campaign against tuberculosis
      in Morocco].
AB  - Tuberculosis is a major public health problem in Marocco, with an incidence of
      100 cases per 100,000 people. Occupational health could make a substantial
      contribution to the national anti-tuberculosis campaign, as the principal aims of
      occupational health are to protect and to improve the physical, mental and social
      well-being of the workforce. Occupational health thus devotes considerable
      attention to the promotion of health in general, and the fight against
      tuberculosis in particular. Occupational health physicians can play a major in
      several areas: prevention, screening, management of patients, compensation and
      epidemiology. The generalization of medical cover in the work environment in
      Morocco requires the application of laws already in place, the creation of
      occupational health departments, the training of occupational health physicians
      and the raising of their awareness concerning the anti-tuberculosis, and the
      involvement of doctors in municipal hygiene offices in the framework of a
      national health program for the entire workforce.

PMID- 11440885
TI  - [Epidemiological, clinical and progressive aspects of asthma observed at Bamako,
      Mali].
AB  - We carried out a prospective study of 106 of the 752 asthmatic patients attending
      the outpatient clinic of Point G Hospital, Bamako, between December 1997 and
      November 1998. We analyzed data for 61 patients whose lung function was assessed
      by measurement of peak expiratory flow. The frequency of asthma was 14.9%,
      suggesting regular progression of the disease. There were slightly more women
      than men (55.7% women) in the study population and the mean age of the patients
      was 31 years. Most of the patients (65.5%) were recruited in the dry season
      (November to May). Based on peak expiratory flow measurements, intermittent
      asthma was the most frequent type of asthma observed (37.8%), followed by
      moderate persistent asthma (34.4%), mild persistent asthma (18%) and severe
      persistent asthma (9.8%). The mean cost per episode of asthma was $36 (US) and
      the mean cost per patient was $432 (US) per year. In 52.45% of cases, the drugs
      required were available and the patient had access to them. They were available
      but not accessible in 26.22% of cases. To improve the management of asthma in
      countries with limited financial resources, generic drugs should be made
      available.

PMID- 11440886
TI  - [Diabetic nephropathy: an epidemiological study based on proteinuria in a
      population of black African diabetics in Cotonou, Benin].
AB  - We evaluated proteinuria to determine the frequency of diabetic nephropathy and
      to study epidemiological aspects of this disease. We measured 24-hour urinary
      protein excretion in 152 diabetic patients. We recorded the age and sex of each
      patient, the duration of diabetes and blood glucose concentration. Proteinuria
      was diagnosed in 28% of the diabetic patients. The frequency of proteinuria was
      higher in men (33%) than in women (19%). The highest frequency (37.5%) was
      observed in subjects aged 70 years or over. In these patients, the higher
      frequency of proteinuria was associated with a longer duration of diabetes.
      However, proteinuria was detected in 28% of patients with diabetes diagnosed less
      than one year previously, suggesting a long period of undiagnosed diabetes in
      these subjects. Finally, proteinuria was more frequent in patients treated with
      insulin (42%) than in those treated orally (25%). Thus, diabetic nephropathy is a
      frequent complication in black diabetic patients in Cotonou. As hemodialysis and
      kidney transplantation are very expensive and access to these treatments is
      limited in developing countries, preventive measures based on optimizing patient
      management and the early diagnosis of diabetes and its complications are
      required.

PMID- 11440887
TI  - [The use of contraceptive methods by the Mossi in a rural health district of
      Kaya, Burkina Faso].
AB  - We investigated contraceptive practices in the rural health district of Kaya in
      Burkina Faso with the aim of a) comparing the sociodemographic and cultural
      characteristics of individuals who were well and poorly informed concerning
      contraceptive methods; b) analyzing the pattern of use of these contraceptive
      methods by the populations. We carried out a two-level cluster survey by the
      Hendersen method. For each household investigated, the chief, his wife (or one
      wife selected at random in polygamous families) and an adolescent (or one
      adolescent selected at random if there was more than one adolescent) were
      interviewed. Significantly more men than women were well informed concerning
      contraceptive methods. Similarly, a higher proportion of male adolescents than of
      female adolescents were well informed concerning contraceptive methods. The
      individuals who were well informed concerning contraceptive methods differed from
      those who were not well informed in terms of age, religion, level of education
      and radio listening habits. The prevalence of use of contraceptive methods in
      this study was found to be 4 to 36%, depending on the group studied. The majority
      of individuals expressed an intention to use contraceptive methods in the future:
      59 to 78%, depending on the group studied. The contraceptive methods chosen for
      current and future use were, in order: the pill, condoms and contraceptive
      implants and the intrauterine device. Current patterns of contraceptive use
      favor, in decreasing order of preference, abstinence, the pill, condoms and
      contraceptive implants. There was also a strong tendency for individuals to
      experiment with diverse contraceptive methods. Thus, in the future, there is
      likely to be a trend towards the abandoning of abstinence in favor of the pill,
      condoms and contraceptive implants. Of these newer methods, condoms are likely to
      be the least popular and their relegation to a lower level of importance is
      likely to have disastrous consequences in terms of the prevention of HIV
      transmission by the sexual route. The results of this study indicate that
      information campaigns concerning contraceptive methods should be refocused on
      women and adolescent girls, condom promotion and maintaining the use of the
      methods chosen in the population.

PMID- 11440889
TI  - [Acute appendicitis at the National University Hospital in Bangui, Central
      African Republic: epidemiologic, clinical, paraclinical and therapeutic aspects].
AB  - We carried out a retrospective study to analyse clinical, paraclinical and
      therapeutic aspects of acute appendicitis cases as the National University
      Hospital (CNHU) at Bangui in the Central African Republic. We compared our
      findings with those for other African countries and for industrialized countries.
      From September 15 1990 to February 15 1992, 285 patients underwent laparotomy to
      treat acute appendicitis. We carried out a study of clinical, paraclinical and
      therapeutic aspects on 57 patients with complete case histories (20% of the
      patients undergoing surgery). The appendices of these patients were sent to the
      Laboratory of Pathological Anatomy of the Faculty of Medicine at Marseille,
      France, for analysis. The frequency of appendectomy among patients undergoing
      visceral surgery by laparotomy with no acute traumatic abdominal syndrome was
      42.3%. The incidence of appendectomy for the city of Bangui in 1991 was 36.5 per
      100,000 inhabitants. These cases of appendicitis were diagnosed essentially on
      clinical grounds. Leukocyte counts exceeded 10,000 per mm3 in 30% of the
      patients. Histological examination revealed the presence of parasites in 10 cases
      : Schistosoma mansoni eggs (seven cases) and Ascaris lumbricoides eggs (one case)
      in patients with acute appendicitis and one case each of Schistosoma mansoni eggs
      and Ascaris lumbricoides eggs at the time of diagnosis but normal histological
      results for the removed appendix. Most of the patients consulted late, a mean of
      four days after the onset of symptoms. The frequency of appendectomy on principle
      was 12.7% and parenteral antibiotic treatment was prescribed systematically
      follow- ing surgery. The mean duration of hospital stay after surgery was 7.6
      days. No early postoperative complications were noted. However, two late
      postoperative complications resulting in the death of the patient were observed,
      giving a mortality rate of 3.5%. These complications were one case of peritonitis
      after appendectomy involving intestinal resection and one case of occlusive
      syndrome with septic shock. The frequency of acute appendicitis at the CNHU at
      Bangui was similar to that reported in another tropical African country (~ 1%).
      However, the incidence of appendectomies at Bangui is lower than generally
      reported for western countries (15 to 40%). Positive diagnosis was made on
      classic data obtained on clinical examination and on associated biological data,
      if available. Parasites were identified on histological examination in some cases
      of acute appendicitis, but it is unclear whether these parasites were actually
      responsible for the appendicitis. Efficient examinations for the exploration of
      acute nonspecific abdominal pain, such as the measurement of inflammation
      indicators, particularly serum activated protein C levels, graded-compression
      ultrasound scans and celioscopy, should be made available in the hospitals of
      African countries to increase the precision of diagnosis and to decrease the
      still too high frequency of appendectomies performed on principle. The
      postoperative mortality rate at the CNHU of Bangui is higher than the low rates
      (0.1 to 0.25%) reported for industrialized countries but is close to those
      reported for African countries. This high rate of mortality results partly from
      the lateness of consultations, because patients in tropical Africa often consult
      a traditional healer before resorting to modern medicine, and partly from
      misdiagnoses.

PMID- 11440890
TI  - [Ketoacidosis coma auguring diabetes in black adults].
AB  - A particular form revealing diabetes mellitus in the black race is described:
      adult's inaugural ketoacidosis requiring a temporary insulin treatment, followed
      by a variable remission stage. We present in this work the clinical and evolutive
      characters of this coma inaugurating diabetes mellitus from twenty seven (27)
      patients of the metabolic diseases departement (CHU-Brazzaville). Among adult
      patients presenting a ketoacidosis coma, the prevalence rate of inaugural form is
      forty two percent (42%). The evolution is marked by a remission stage varying
      between six months and seven years.

PMID- 11440892
TI  - [Pneumatosis cystoides intestinalis: the first case in Congo].
AB  - We report the first congolese case of intestinal cystic pneumatosis diagnosis at
      a patient of 64 years who was hospitalized for a glairo-sanguinolent diarrhea, of
      diffuse abdominal pains and meteorism. Diagnosis was confirmed by the coloscopy
      which showed polypoides formings to fine, translucent walls, depressibles, and
      for intestinal opacification which showed parietales incomplete images of the
      left colonist. Evolution was favorable under metronidazol and ciprofloxacin. The
      coloscopy of control did not find a recurrence.

PMID- 11440893
TI  - [A new decision support tool in the campaign against maternal mortality: the
      Dystocia Risk Score].
AB  - At Ziguinchor Regional Hospital (ZRH) in Senegal, 80% of maternal deaths are
      associated with late referral of dystocia cases. The gynecology and obstetrics
      team of the ZRH, in collaboration with the teaching staff of the Institute of
      Health and Development (ISED), tried to find ways to combat maternal mortality
      and stillbirth, based on double-entry contigency tables and a logical framework.
      We developed a tool more elaborate than a simple decision tree: the dystocial
      risk score. This tool has three components: A column provides a list of eight
      characteristics to check for in the woman: history of cesarean section, limping,
      less than 150 cm in height, no living child, less than 18 years old, more than 35
      years old, other risk factors, no risk factors. A horizontal section provides a
      checklist of possible outcomes of the pregnancy itself: obstacle praevia,
      precedence, noncephalic presentation, uterine length of over 35 cm, loss of
      amniotic fluid over 12 hours or more, other abnormalities, no abnormalities. A
      rectangular grid indicates the prognosis. This grid consists of three zones: a
      large blue zone (dangerous), a medium-sized grey zone (doubtful) and a small blue
      zone (hopeful). A positive DRS is obtained if there is at least one cross in the
      dangerous zone and/or at least two crosses in the doubtful zone. If these
      conditions are not fulfilled, the DRS is negative. A positive DRS indicates that
      the woman should be referred to a center specialized in obstetric emergency care.
      This tool was validated in a study of 376 pregnant women carried out over a
      period of six months. It was found to have a sensitivity of 83.6%, a specificity
      of 90.1%, a positive predictive value of 72.3% and a negative predictive value of
      94.1%. The DRS is a simple, easy-to-use decision-making tool. The large-scale use
      of this tool (by midwives, chief nurses and health workers) would accelerate the
      identification of pregnant women with a high risk of dystocia. The timely
      referral of these women to specialized emergency obstetrics centers would
      increase the efficacy of care and would reduce the levels of maternal mortality
      and stillbirth.

PMID- 11440894
TI  - Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to
      resistance exercise.
AB  - The present study was designed to determine whether consumption of an oral
      essential amino acid-carbohydrate supplement (EAC) before exercise results in a
      greater anabolic response than supplementation after resistance exercise. Six
      healthy human subjects participated in two trials in random order, PRE (EAC
      consumed immediately before exercise), and POST (EAC consumed immediately after
      exercise). A primed, continuous infusion of L-[ring-(2)H(5)]phenylalanine,
      femoral arteriovenous catheterization, and muscle biopsies from the vastus
      lateralis were used to determine phenylalanine concentrations, enrichments, and
      net uptake across the leg. Blood and muscle phenylalanine concentrations were
      increased by approximately 130% after drink consumption in both trials. Amino
      acid delivery to the leg was increased during exercise and remained elevated for
      the 2 h after exercise in both trials. Delivery of amino acids (amino acid
      concentration times blood flow) was significantly greater in PRE than in POST
      during the exercise bout and in the 1st h after exercise (P < 0.05). Total net
      phenylalanine uptake across the leg was greater (P = 0.0002) during PRE (209 +/-
      42 mg) than during POST (81 +/- 19). Phenylalanine disappearance rate, an
      indicator of muscle protein synthesis from blood amino acids, increased after EAC
      consumption in both trials. These results indicate that the response of net
      muscle protein synthesis to consumption of an EAC solution immediately before
      resistance exercise is greater than that when the solution is consumed after
      exercise, primarily because of an increase in muscle protein synthesis as a
      result of increased delivery of amino acids to the leg.

PMID- 11440895
TI  - TZDs inhibit vascular smooth muscle cell growth independently of the cyclin
      kinase inhibitors p21 and p27.
AB  - The thiazolidenediones (TZDs) are commonly used to treat hyperglycemia in type 2
      diabetes. Diabetes is associated with macrovascular disease, leading to
      accelerated atherosclerosis caused by aberrant vascular smooth muscle (VSM) cell
      proliferation. Although VSM cell proliferation is inhibited by the TZDs, the
      mechanism of this effect has not been established. Because of reports that the
      cyclin kinase inhibitors (CKIs) p21(Waf1/Cip1) and p27(Kip1) can exhibit both
      growth-inhibitory and growth-permissive effects in VSM cells, we asked whether
      alterations in these cell cycle regulatory proteins are the mechanism by which
      the TZDs inhibit VSM cell growth. We show that platelet-derived growth factor-BB
      increases p21 and p27 and that this increase is attenuated by TZDs. Surprisingly,
      when VSM cells were transfected with antisense oligodeoxynucleotides to p21 and
      p27, inhibition of DNA synthesis by TZDs occurred to the same degree as in
      control cells. Furthermore, the TZDs have inhibitory effects on cyclin D1 and
      cyclin E levels, suggesting another mechanism by which these drugs decrease VSM
      cell growth. These data suggest that the TZD-mediated reduction in CKI levels is
      not the sole mechanism for their antiproliferative effects. The observed decrease
      in levels of the G1 cyclins by the TZDs suggests a possible mechanism of VSM cell
      growth inhibition.

PMID- 11440896
TI  - Fetal hyperinsulinemia increases farnesylation of p21 Ras in fetal tissues.
AB  - Even though the role of fetal hyperinsulinemia in the pathogenesis of fetal
      macrosomia in patients with overt diabetes and gestational diabetes mellitus
      seems plausible, the molecular mechanisms of action of hyperinsulinemia remain
      largely enigmatic. Recent indications that hyperinsulinemia "primes" various
      tissues to the mitogenic influence of growth factors by increasing the pool of
      prenylated Ras proteins prompted us to investigate the effect of fetal
      hyperinsulinemia on the activitiy of farnesyltransferase (FTase) and the amounts
      of farnesylated p21 Ras in fetal tissues in the ovine experimental model.
      Induction of fetal hyperinsulinemia by direct infusion of insulin into the fetus
      and by either fetal or maternal infusions of glucose resulted in significant
      increases in the activity of FTase and the amounts of farnesylated p21 Ras in
      fetal liver, skeletal muscle, fat, and white blood cells. An additional infusion
      of somatostatin into hyperglycemic fetuses blocked fetal hyperinsulinemia and
      completely prevented these increases, specifying insulin as the causative factor.
      We conclude that the ability of fetal hyperinsulinemia to increase the size of
      the pool of farnesylated p21 Ras may prime fetal tissues to the action of other
      growth factors and thereby constitute one mechanism by which fetal
      hyperinsulinemia could induce macrosomia in diabetic pregnancies.

PMID- 11440897
TI  - Effects of ischemia on sarcoplasmic reticulum Ca(2+) uptake and Ca(2+) release in
      rat skeletal muscle.
AB  - In this study, we investigated the hypothesis that prolonged ischemia would
      impair both sarcoplasmic reticulum (SR) Ca(2+) uptake and Ca(2+) release in
      skeletal muscle. To induce total ischemia (I), a tourniquet was placed around the
      upper hindlimb in 30 female Sprague-Dawley rats [wt = 256 +/- 6.7 (SE) g] and
      inflated to 350 mmHg for 4 h. The contralateral limb served as control (C).
      Immediately after the 4 h of ischemia, mixed gastrocnemius and tibialis anterior
      muscle was sampled from both limbs, and both crude muscle homogenates and SR
      vesicles were prepared. In another 10 control animals (CC), muscles were sampled
      and prepared exactly the same way, but immediately after anesthetization. Ca(2+)
      uptake and Ca(2+) release were measured in vitro with Indo-I on both homogenates
      and SR vesicles. As hypothesized, submaximal Ca(2+) uptake was lower (P < 0.05)
      in I compared with CC and C, by 25 and 45% in homogenates and SR vesicles,
      respectively. Silver nitrate (AgNO(3))-induced Ca(2+) release, which occurred in
      two phases (phase 1 and phase 2), was also altered in I compared with CC and C,
      in both muscle homogenates and SR vesicles. With ischemia, phase 1 peak Ca(2+)
      release was 26% lower (P < 0.05) in SR vesicles only. For phase 2, peak Ca(2+)
      release was 54 and 24% lower (P < 0.05) in SR vesicles and homogenates,
      respectively. These results demonstrate that prolonged skeletal muscle ischemia
      leads to a reduced SR Ca(2+) uptake in both homogenates and SR vesicles. The
      effects of ischemia on SR Ca(2+) release, however, depend on both the phase
      examined and the type of tissue preparation.

PMID- 11440898
TI  - Recovery of (13)CO(2) from infused [1-(13)C]leucine and [1,2-(13)C(2)]leucine in
      healthy humans.
AB  - Carbon (C) in the 1-position of leucine is released as CO(2) with the
      decarboxylation of alpha-ketoisocaproate (KIC). Carbon in the 2-position of
      leucine undergoes several additional metabolic steps before entering the
      tricarboxylic acid (TCA) cycle in the 1-position of acetyl-CoA, where it can be
      released as CO(2) or be incorporated into other compounds. This study examined
      the metabolic fate of C in the 2-position of leucine. We infused 11 healthy
      subjects with [1-(13)C]leucine and [1,2-(13)C(2)]leucine for 3.5--4 h to measure
      leucine kinetics and the oxidation of the tracers from enrichments of (13)C in
      blood and expired CO(2). The fraction of leucine infused that was oxidized
      (f(ox)) was used to define the degree of recovery of the (13)C label(s) for each
      tracer. As expected, leucine appearance (means +/- SE) did not differ between
      tracers ((13)C(1): 92.1 +/- 3.1 vs. (13)C(2): 89.2 +/- 3.2 micromol x kg(-1) x h(
      1)) when calculated using plasma leucine enrichments as an index of intracellular
      enrichment. A small (3%) but significant (P = 0.048) difference between tracers
      was found when KIC was used to calculate leucine appearance ((13)C(1): 118.0 +/-
      4.1 vs. (13)C(2): 114.4 +/- 4.5 micromol x kg(-1) x h(-1)). The value of f(ox)
      was 14 +/- 1% for [1,2-(13)C(2)]leucine and was lower than the f(ox) for [1
      (13)C]leucine (19 +/- 1%). From the f(ox) data, we calculated that the recovery
      of the 2-(13)C label in breath CO(2) was 58 +/- 6% relative to the 1-(13)C label.
      These findings show that, although a majority of the 2-(13)C label of leucine is
      recovered in breath CO(2), a significant percentage (approximately 42%) is
      retained in the body, presumably by transfer to other compounds, via TCA exchange
      reactions.

PMID- 11440899
TI  - GLP-1-induced alterations in the glucose-stimulated insulin secretory dose
      response curve.
AB  - The present study was undertaken to establish in normal volunteers the
      alterations in beta-cell responsiveness to glucose associated with a constant
      infusion of glucagon-like peptide-1 (GLP-1) or a pretreatment infusion for 60
      min. A high-dose graded glucose infusion protocol was used to explore the dose
      response relationship between glucose and insulin secretion. Studies were
      performed in 10 normal volunteers, and insulin secretion rates (ISR) were
      calculated by deconvolution of peripheral C-peptide levels by use of a two
      compartmental model that utilized mean kinetic parameters. During the saline
      study, from 5 to 15 mM glucose, the relationship between glucose and ISR was
      linear. Constant GLP-1 infusion (0.4 pmol x kg(-1) x min(-1)) shifted the dose
      response curve to the left, with an increase in the slope of this curve from 5 to
      9 mM glucose from 71.0 +/- 12.4 pmol x min(-1) x mM(-1) during the saline study
      to 241.7 +/- 36.6 pmol x min(-1) x mM(-1) during the constant GLP-1 infusion (P <
      0.0001). GLP-1 consistently stimulated a >200% increase in ISR at each 1 mM
      glucose interval, maintaining plasma glucose at <10 mM (P < 0.0007). Pretreatment
      with GLP-1 for 60 min resulted in no significant priming of the beta-cell
      response to glucose (P = 0.2). Insulin clearance rates were similar in all three
      studies at corresponding insulin levels. These studies demonstrate that
      physiological levels of GLP-1 stimulate glucose-induced insulin secretion in a
      linear manner, with a consistent increase in ISR at each 1 mM glucose interval,
      and that they have no independent effect on insulin clearance and no priming
      effect on subsequent insulin secretory response to glucose.

PMID- 11440900
TI  - Energy nutrients modulate the splanchnic sequestration of dietary nitrogen in
      humans: a compartmental analysis.
AB  - We used a previously developed compartmental model to assess the postprandial
      distribution and metabolism of dietary nitrogen (N) in the splanchnic and
      peripheral areas after the ingestion of a single meal containing milk protein
      either alone (MP) or with additional sucrose (SMP) or fat (FMP). The addition of
      fat was predicted to enhance splanchnic dietary N anabolism only transiently,
      without significantly affecting the global kinetics of splanchnic retention and
      peripheral uptake. In contrast, the addition of sucrose, which induced
      hyperinsulinemia, was predicted to enhance dietary N retention and anabolism in
      the splanchnic bed, thus leading to reduced peripheral dietary amino acid
      availability and anabolism. The incorporation of dietary N into splanchnic
      proteins was thus predicted to reach 18, 24, and 35% of ingested N 8 h after MP,
      FMP, and SMP, respectively. Such a model provides insight into the dynamics of
      the system in the nonsteady postprandial state and constitutes a useful,
      explanatory tool to determine the region-specific utilization of dietary N under
      different nutritional conditions.

PMID- 11440901
TI  - Metabolic handling of intraduodenal vs. intravenous glucose in humans.
AB  - To determine whether the route of glucose administration affects whole body
      glucose metabolism, 14 healthy volunteers were randomly infused with
      intraduodenal (id) or intravenous (iv) glucose at 6 mg x kg(-1) x min(-1) for 180
      min. Infused glucose was labeled with [2-(3)H]glucose in a first series of paired
      experiments designed to characterize kinetic parameters to be used in a second
      series of experiments in which [3-(3)H]- and [U-(14)C]glucose labeling was used
      to characterize the metabolic fate of infused glucose. Experiments with [2
      (3)H]glucose showed that, after a lag period of only 20 min, id absorption
      averaged 105 +/- 3% of infusion. During the final hour of id and iv infusion of
      [3-(3)H]glucose, tissue uptake averaged 98 +/- 3 and 107 +/- 4% of infusion,
      respectively, and was equally divided between glycolysis ((3)H(2)O production)
      and storage (uptake-glycolysis). Glucose oxidation ((14)CO(2)), total
      carbohydrate oxidation (indirect calorimetry), and net carbohydrate balance were
      also similar, but the thermic effect of glucose was significantly greater after
      id infusion. Because insulin and estimated portal vein glucose levels were
      similar during the final 80 min of both infusions, our results suggest that
      hepatic glucose storage (and therefore muscle storage estimated as whole body
      minus liver storage) is not affected by the route of glucose administration.

PMID- 11440902
TI  - Involvement of thioredoxin in the regulation of growth hormone secretion in rat
      pituitary cell cultures.
AB  - We report here an examination of the effect of thioredoxin (TRX) on the secretion
      of growth hormone (GH) from rat anterior pituitary cells in vitro. Treatment of
      rat pituitary cells with growth hormone-releasing factor (GRF), but not GH, led
      to a significant increase in intracellular TRX protein levels. GRF, recombinant
      human TRX (rhTRX), and a combination thereof were all shown to induce immediate
      GH secretion from pituitary cells, as evidenced by perifusion experiments. RhTRX,
      but not other reducing agents such as beta-mercaptoethanol and N-acetyl-L
      cysteine, augmented GRF-stimulated and -unstimulated GH secretion from rat
      pituitary cells in a dose-dependent manner. RhTRX did not significantly affect
      the GH mRNA expression of pituitary cells stimulated in the presence or absence
      of GRF. In addition, rhTRX-augmented GH secretion was not significantly affected
      by the presence of cycloheximide. Collectively, these findings suggest that TRX
      is induced by stimulation with GRF and plays a regulatory role in GH secretion
      from rat anterior pituitary cells by enhancing the secretion of stored GH, rather
      than by the synthesis of GH.

PMID- 11440903
TI  - Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin.
AB  - High-fat feeding has been shown to cause hepatic insulin resistance. The aims of
      this study were to investigate the biochemical steps responsible for enhanced
      gluconeogenesis as a result of increased dietary fat intake and the site or sites
      at which the antihyperglycemic agent metformin acts to inhibit this process. Male
      Hooded Wistar rats were fed either a standard chow diet (5% fat by weight) or a
      high-fat diet (60% fat by weight) for 14 days with or without metformin. Total
      endogenous glucose production and gluconeogenesis were determined using [6
      (3)H]glucose and [U-(14)C]alanine, respectively. Gluconeogenic enzyme activity
      and, where appropriate, protein and mRNA levels were measured in liver tissues.
      The high-fat diet increased endogenous glucose production (21.9 +/- 4.4 vs. 32.2
      +/- 4.8 micromol x kg(-1) x min(-1), P < 0.05) and alanine gluconeogenesis (4.5
      +/- 0.9 vs. 9.6 +/- 1.9 micromol x kg(-1) x min(-1), P < 0.05). Metformin reduced
      both endogenous glucose production (32.2 +/- 4.8 vs. 16.1 +/- 2.1 micromol x kg(
      1) x min(-1), P < 0.05) and alanine gluconeogenesis (9.6 +/- 1.9 vs. 4.7 +/- 0.8
      micromol x kg(-1) x min(-1), P < 0.05) after high-fat feeding. These changes were
      reflected in liver fructose-1,6-bisphosphatase protein levels (4.5 +/- 0.9 vs.
      9.6 +/- 1.9 arbitrary units, P < 0.05 chow vs. high-fat feeding; 9.5 +/- 1.9 vs.
      4.7 +/- 0.8 arbitrary units, P < 0.05 high fat fed in the absence vs. presence of
      metformin) but not in changes to the activity of other gluconeogenic enzymes.
      There was a significant positive correlation between alanine gluconeogenesis and
      fructose-1,6-bisphosphatase protein levels (r = 0.56, P < 0.05). Therefore,
      excess supply of dietary fat stimulates alanine gluconeogenesis via an increase
      in fructose-1,6-bisphosphatase protein levels. Metformin predominantly inhibits
      alanine gluconeogenesis by preventing the fat-induced changes in fructose-1,6
      bisphosphatase levels.

PMID- 11440904
TI  - IGF-binding protein-5 stimulates osteoblast activity and bone accretion in
      ovariectomized mice.
AB  - Insulin-like growth factor binding protein-5 (IGFBP-5) is an osteoblast secretory
      protein that becomes incorporated into the mineralized bone matrix. In osteoblast
      cultures, IGFBP-5 stimulates cell proliferation by an IGF-independent mechanism.
      To evaluate whether IGFBP-5 can stimulate osteoblast activity and enhance bone
      accretion in a mouse model of osteoblast insufficiency, daily subcutaneous
      injections of either intact [IGFBP-5 (intact)] or carboxy-truncated IGFBP-5
      [IGFBP-5-(1--169)] were given to ovariectomized (OVX) mice for 8 wk. Femur and
      spine bone mineral density (BMD), measured every 2 wk, showed early and sustained
      increases in response to IGFBP-5. Bone histomorphometry of cancellous bone showed
      significant elevations in the bone formation rate in both the femur metaphysis
      [IGFBP-5- (1)] only) and spine compared with OVX controls. IGFBP-5 also
      stimulated osteoblast number in the femur IGFBP-5-(1--169) only) and spine. These
      data indicate that IGFBP-5 effectively enhances bone formation and bone accretion
      in OVX mice by stimulating osteoblast activity. The finding that IGFBP-5-(1--169)
      is bioactive in vivo indicates that the carboxy-terminal portion is not required
      for this bone anabolic effect.

PMID- 11440905
TI  - Differential gene expression in a murine model of cancer cachexia.
AB  - Murine adenocarcinoma 16 (MAC16) tumors and cell lines induce cachexia in NMRI
      nude mice, whereas histologically similar MAC13 tumors do not. After confirming
      these findings in BALB/c nude mice, we demonstrated that this tissue wasting was
      not related to decreased food intake or increased total body oxidative
      metabolism. Previous studies have suggested that MAC16's cachexigenic properties
      may involve the production of tumor-specific factors. We therefore screened for
      genes having increased expression in the MAC16 compared with the MAC13 cell line
      by performing hybridization to a murine cDNA expression array, by generation and
      comparison of cDNA libraries from each cell line, and by PCR-based subtractive
      hybridization. Northern blot hybridization was performed to confirm differences
      in transcript expression. Transcripts encoding insulin-like growth factor binding
      protein-4, cathepsin B, ferritin light and heavy chain, endogenous long-terminal
      repeat sequences, and a viral envelope glycoprotein demonstrated increased
      expression in the MAC16 cell line. The roles of a number of these genes in known
      metabolic pathways identify them as potential participants in the induction of
      cachexia.

PMID- 11440906
TI  - Assessment of islet beta-cell mass in isolated rat pancreases perfused with D
      [(3)H]mannoheptulose.
AB  - D-mannoheptulose is apparently transported into cells mainly at the intervention
      of GLUT-2 and hence was recently proposed as a tool to label preferentially
      insulin-producing beta-cells in the pancreatic gland. The validity of such a
      proposal was investigated in the present study conducted in isolated perfused
      pancreatic glands from control and streptozotocin-induced diabetic rats. After a
      30-min equilibration period, D-[(3)H]mannoheptulose (0.1 mM) and [U-(14)C]sucrose
      (0.5 mM) were infused for 15 min in the presence of 30 mM D-glucose. The
      pancreatic glands were then perfused for 10 min with a nonradioactive medium
      during and after administration of cytochalasin B (0.02 mM). Under these
      experimental conditions, the intracellular distribution space of D
      [(3)H]mannoheptulose averaged 5.42 +/- 0.75 nl/mg in control animals, whereas it
      failed to be significantly different from zero in the streptozotocin rats. The
      present procedure may thus allow the assessment of the relative contribution of
      islet beta-cells to the total mass of the pancreatic gland.

PMID- 11440907
TI  - Novel gastroinsular axis involving a gastric transmural glucose flux and vagal
      mediation.
AB  - To determine whether the appearance of nutrients into the gastric lumen per se
      provokes insulin secretion, glucose solution was instilled into the pylorus
      cannulated stomach via an orogastric tube in anesthetized dogs. When 200 ml of 0,
      5, 10, and 20% glucose solution were sequentially instilled, transgastric
      gradients (TGG) of plasma glucose concentration across the fundus [short gastric
      vein (SGV) - femoral artery, TGG(SGV)] and insulin levels in the superior
      pancreaticoduodenal vein (SPDV) increased stepwise. Upon instillation of 300 ml
      of 10% glucose, but not 1.8% saline, for 12 min followed by 48-min spontaneous
      drainage via the cannula (n = 5 each), TGG(SGV) and insulin levels in the SPDV
      increased concomitantly and significantly by 0.95 mM and 1,334 pM (mean),
      respectively, regardless of unaltered arterial glucose levels. The amount of
      secreted insulin (area under the curve) significantly correlated with the maximum
      TGG(SGV) (r = 0.693). In selectively gastric-vagotomized dogs (n = 5), insulin
      levels in the SPDV did not increase upon instillation despite a TGG(SGV) rise
      comparable to that in normal dogs. These results indicate that intragastric
      glucose appearance provokes vagus-mediated insulin secretion probably related to
      the transfundic glucose flux, suggesting the presence of a novel neurogenic
      gastroinsular axis.

PMID- 11440908
TI  - 1,25-Dihydroxyvitamin D(3) downregulates the rat intestinal vitamin D(3)-25
      hydroxylase CYP27A.
AB  - The vitamin D(3)-25-hydroxylase CYP27A is located predominantly in liver, but its
      expression is also detected in extrahepatic tissues. Our aim was to evaluate the
      regulation of CYP27A by vitamin D(3) (D(3)) or its metabolites in rat duodena.
      Vitamin D-depleted rats were repleted with D(3), 25-hydroxyvitamin D (25OHD), or
      1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] or acutely injected 1,25(OH)(2)D(3)
      to investigate the mechanisms of action of the hormone. All D(3) compounds led to
      a progressive decrease in CYP27A mRNA, with levels after D(3) representing 20% of
      that observed in D depletion. 25OHD decreased CYP27A mRNA by 55%, whereas
      1,25(OH)(2)D(3) led to a 40% decrease, which was accompanied by a 31% decrease in
      CYP27A protein levels and an 89% decrease in enzyme activity. Peak circulating
      1,25(OH)(2)D(3) concentrations were, however, the highest in D(3)-repleted,
      followed by 25OHD- and 1,25(OH)(2)D(3)-repleted animals. 1,25(OH)(2)D(3) resulted
      in a decrease in both CYP27A mRNA half-life and transcription rate. Our data
      illustrate that the intestine expresses the D(3)-25-hydroxylase and that the gene
      is highly regulated in vivo through a direct action of 1,25(OH)(2)D(3) or through
      the local production of D(3) metabolites.

PMID- 11440909
TI  - Prenatal cytokine exposure results in obesity and gender-specific programming.
AB  - Prenatal events appear to program hormonal homeostasis, contributing to the
      development of somatic disorders at an adult age. The aim of this study was to
      examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be
      followed by hormonal consequences in the offspring at adult age. Pregnant rats
      were injected on days 8, 10, and 12 of gestation with either human interleukin-6
      (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were
      injected with vehicle. All exposed offspring developed increased body weight (P <
      0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight
      (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6
      group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone
      suppression test results. In male rats, insulin sensitivity was decreased after
      IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha
      group (P < 0.01). In female rats, plasma testosterone levels were higher in all
      exposed groups compared with controls (P < 0.01--0.001), with the exception of
      Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor
      activity (P < 0.05), and females in the IL-6 group showed increased locomotor
      activity (P < 0.05). These results indicate that prenatal exposure to cytokines
      or Dxm leads to increased fat depots in both genders. In females, cytokine
      exposure was followed by a state of hyperandrogenicity. The results suggest that
      prenatal exposure to cytokines or Dxm can induce gender-specific programming of
      neuroendocrine regulation with consequences in adult life.

PMID- 11440910
TI  - Regulation of fatty acid oxidation and glucose metabolism in rat soleus muscle:
      effects of AICAR.
AB  - Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside
      (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases
      the rate of fatty acid oxidation in skeletal muscle of fed rats. The present
      study investigated the mechanism by which this occurs and, in particular, whether
      changes in the activity of malonyl-CoA decarboxylase (MCD) and the beta-isoform
      of acetyl-CoA carboxylase (ACC beta) are involved. In addition, the relationship
      between changes in fatty acid oxidation induced by AICAR and its effects on
      glucose uptake and metabolism was examined. In incubated soleus muscles isolated
      from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased
      ACC beta activity (40%) and malonyl-CoA concentration (50%); however, MCD
      activity was not significantly altered. In soleus muscles from overnight-fasted
      rats, AICAR decreased ACC beta activity (40%), as it did in fed rats; however, it
      had no effect on the already high rate of fatty acid oxidation or the low malonyl
      CoA concentration. In keeping with its effect on fatty acid oxidation, AICAR
      decreased glucose oxidation by 44% in fed rats but did not decrease glucose
      oxidation in fasted rats. It had no effect on glucose oxidation when fatty acid
      oxidation was inhibited by 2-bromopalmitate. Surprisingly, AICAR did not
      significantly increase glucose uptake or assayable AMP-activated protein kinase
      activity in incubated soleus muscles from fed or fasted rats. These results
      indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or
      stimulate glucose uptake as it does in extensor digitorum longus and
      epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation
      and diminish glucose oxidation and malonyl-CoA concentration is dependent on the
      nutritional status of the rat, and 3) the ability of AICAR to diminish assayable
      ACC activity is independent of nutritional state.

PMID- 11440911
TI  - Sulfate production depicts fed-state adaptation to protein restriction in humans.
AB  - One feature of the adaptation to dietary protein restriction is reduced urea
      production over the hours after consumption of a test meal of fixed composition.
      This adaptation is impaired in conventionally treated insulin-dependent diabetes
      mellitus (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol Endocrinol Metab
      272: E59--E67, 1997). We have now tested the response to a test meal containing
      less protein and included as a main outcome variable the production of sulfate, a
      specific indicator of sulfur amino acid catabolism. Six normal men consumed a
      mixed test meal containing 0.25 g protein/kg and 10 kcal/kg while adapted to high
      (1.5 g x kg(-1) x day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes.
      They followed the identical protocol twice. Six subjects with insulin-dependent
      diabetes consumed the test meal while adapted to their customary high-protein
      diet. Adaptation to protein restriction reproducibly reduced 9-h cumulative
      postmeal urea N and S production by 22--29% and 49--52%, respectively (both P <
      0.05). Similar results were obtained for a postmeal collection period of 6 h. The
      response of the diabetic subjects was normal. We conclude that reductions in
      postmeal urea and sulfate production after protein restriction are reproducible
      and are evident using a postmeal collection period as short as 6 h. Sulfate
      production effectively depicts fed-state adaptation to protein restriction.

PMID- 11440912
TI  - Effect of protein restriction on (15)N transfer from dietary [(15)N]alanine and
      [(15)N]Spirulina platensis into urea.
AB  - Six normal men consumed a mixed test meal while adapted to high (1.5 g. kg(-1) x
      day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes. They completed this
      protocol twice: when the test meals included 3 mg/kg of [(15)N]alanine
      ([(15)N]Ala) and when they included 30 mg/kg of intrinsically labeled
      [(15)N]Spirulina platensis ([(15)N]SPI). Six subjects with insulin-dependent
      diabetes mellitus (IDDM) receiving conventional insulin therapy consumed the test
      meal with added [(15)N]Ala while adapted to their customary high-protein diet.
      Protein restriction increased serum alanine, glycine, glutamine, and methionine
      concentrations and reduced those of leucine. Whether the previous diet was high
      or low in protein, there was a similar increase in serum alanine, methionine, and
      branched-chain amino acid concentrations after the test meal and a similar
      pattern of (15)N enrichment in serum amino acids for a given tracer. When
      [(15)N]Ala was included in the test meal, (15)N appeared rapidly in serum alanine
      and glutamine, to a minor degree in leucine and isoleucine, and not at all in
      other circulating amino acids. With [(15)N]SPI, there was a slow appearance of
      the label in all serum amino acids analyzed. Despite the different serum amino
      acid labeling, protein restriction reduced the postmeal transfer of dietary (15)N
      in [(15)N]Ala or [(15)N]SPI into [(15)N]urea by similar amounts (38 and 43%,
      respectively, not significant). The response of the subjects with IDDM was
      similar to that of the normal subjects. Information about adaptive reductions in
      dietary amino acid catabolism obtained by adding [(15)N]Ala to a test meal
      appears to be equivalent to that obtained using an intrinsically labeled protein
      tracer.

PMID- 11440913
TI  - Chylomicron metabolism by the isolated perfused mouse heart.
AB  - The catabolism of rat chylomicrons, labeled in their triacylglycerol (TG)
      component, was investigated using perfused working mouse hearts. Perfusion of
      mouse hearts with heparin increased lipoprotein lipase (LPL) activity in the
      perfusate. This heparin-releasable LPL pool remained constant over a variety of
      experimental conditions, including workload and fatty acid concentrations, making
      the mouse heart a suitable model to study chylomicron catabolism. Endothelium
      bound LPL hydrolyzed radiolabeled (3)H-labeled chylomicrons (0.4 mM TG); the fate
      of LPL-derived (3)H-labeled fatty acids was split evenly between oxidation
      (production of (3)H(2)O) and esterification (incorporation into tissue lipids,
      mainly TG). In comparison, the oxidation of 0.4 mM [(3)H]palmitate complexed to
      albumin was fourfold greater than esterification into tissue lipids.
      Surprisingly, the addition of unlabeled palmitate (0.4 or 1.2 mM) to perfusions
      with (3)H-chylomicrons did not affect the fate (either oxidation or
      esterification) of LPL-derived (3)H-fatty acids. These results suggest that fatty
      acids produced from lipoprotein hydrolysis by the action of LPL and fatty acids
      from a fatty acid-albumin complex do not enter a common metabolic pool in the
      heart.

PMID- 11440914
TI  - BCAA intake affects protein metabolism in muscle after but not during exercise in
      humans.
AB  - Branched-chain amino acids (BCAA) or a placebo was given to seven subjects during
      1 h of ergometer cycle exercise and a 2-h recovery period. Intake of BCAA did not
      influence the rate of exchange of the aromatic amino acids, tyrosine and
      phenylalanine, in the legs during exercise or the increase in their concentration
      in muscle. The increase was approximately 30% in both conditions. On the other
      hand, in the recovery period after exercise, a faster decrease in the muscle
      concentration of aromatic amino acids was found in the BCAA experiment (46%
      compared with 25% in the placebo condition). There was also a tendency to a
      smaller release (an average of 32%) of these amino acids from the legs during the
      2-h recovery. The results suggest that BCAA have a protein-sparing effect during
      the recovery after exercise, either that protein synthesis has been stimulated
      and/or protein degradation has decreased, but the data during exercise are too
      variable to make any conclusions about the effects during exercise. The effect in
      the recovery period does not seem to be mediated by insulin.

PMID- 11440915
TI  - Lack of hepatic "interregulation" during inhibition of glycogenolysis in a canine
      model.
AB  - It has been proposed that the glycogenolytic and gluconeogenic pathways
      contributing to endogenous glucose production are interrelated. Thus a change in
      one source of glucose 6-phosphate might be compensated for by an inverse change
      in the other pathway. We therefore investigated the effects of 1,4-dideoxy-1,4
      imino-D-arabinitol (DAB), a potent glycogen phosphorylase inhibitor, on glucose
      production in fasted conscious dogs. When dogs were treated acutely with high
      glucagon, glucose production rose from 1.93 +/- 0.14 to 3.07 +/- 0.37 mg x kg(-1)
      x min(-1) (P < 0.01). When dogs were treated acutely with DAB in addition to high
      glucagon infusion, the stimulation of the glycogenolytic rate was completely
      suppressed. Glucose production rose from 1.85 +/- 0.20 to 2.41 +/- 0.17 mg x kg(
      1) x min(-1) (P < 0.05), which was due to the increase in gluconeogenesis from
      0.93 +/- 0.09 to 1.54 +/- 0.08 mg x kg(-1) x min(-1) (P < 0.001). In conclusion,
      infusion of DAB inhibited glycogenolysis; however, the absolute contribution of
      gluconeogenesis to glucose production was not affected. These results suggest
      that inhibition of glycogenolysis could be an effective antidiabetic treatment.

PMID- 11440916
TI  - Efficacy of bright light and sleep/darkness scheduling in alleviating circadian
      maladaptation to night work.
AB  - We tested the hypothesis that circadian adaptation to night work is best achieved
      by combining bright light during the night shift and scheduled sleep in darkness.
      Fifty-four subjects participated in a shift work simulation of 4 day and 3 night
      shifts followed by a 38-h constant routine (CR). Subjects received 2,500 lux
      (Bright Light) or 150 lux (Room Light) during night shifts and were scheduled to
      sleep (at home in darkened bedrooms) from 0800 to 1600 (Fixed Sleep) or ad
      libitum (Free Sleep). Dim light melatonin onset (DLMO) was measured before and
      after the night shifts. Both Fixed Sleep and Bright Light conditions
      significantly phase delayed DLMO. Treatments combined additively, with light
      leading to larger phase shifts. Free Sleep subjects who spontaneously adopted
      consistent sleep schedules adapted better than those who did not. Neither
      properly timed bright light nor fixed sleep schedules were consistently
      sufficient to shift the melatonin rhythm completely into the sleep episode.
      Scheduling of sleep/darkness should play a major role in prescriptions for
      overcoming shift work-related phase misalignment.

PMID- 11440917
TI  - Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome
      (PCOS).
AB  - Women with polycystic ovary syndrome (PCOS) are insulin resistant secondary to a
      postbinding defect in insulin signaling. Sequential euglycemic glucose clamp
      studies at 40 and 400 mU. m(-2). min(-1) insulin doses with serial skeletal
      muscle biopsies were performed in PCOS and age-, weight-, and ethnicity-matched
      control women. Steady-state insulin levels did not differ, but insulin-mediated
      glucose disposal was significantly decreased in PCOS women (P < 0.05). Insulin
      receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3K)
      activity was significantly decreased in PCOS (n = 12) compared with control
      skeletal muscle (n = 8; P < 0.05). There was no significant difference in the
      abundance of IR, IRS-1, or the p85 regulatory subunit of PI 3K in PCOS (n = 14)
      compared with control (n = 12) muscle. The abundance of IRS-2 was significantly
      increased (P < 0.05) in PCOS skeletal muscle, suggesting a compensatory change.
      We conclude that there is a physiologically relevant defect in insulin receptor
      signaling in PCOS that is independent of obesity and type 2 diabetes mellitus.

PMID- 11440918
TI  - Renal clearance of endogenous leptin in hypertensive humans with or without renal
      artery stenosis.
AB  - In humans, the kidney is involved in leptin clearance from the body. The present
      study was performed to assess the renal extraction of leptin in hypertensive
      patients with or without renal artery stenosis. Sixty-five hypertensive subjects
      (39 males and 26 females) underwent catheterization of the renal artery and both
      renal veins with blood sampling for measuring leptin levels. Blood flow to both
      kidneys was measured by the xenon washout technique. From these data, renal
      leptin uptake and renal fractional extraction of leptin were calculated.
      Endogenous creatinine clearance ranged from 24 to 191 ml/min in the males and
      from 20 to 149 ml/min in the females. In 25 patients, radiological signs of renal
      artery stenosis were present. Total renal leptin uptake by both kidneys averaged
      141 +/- 47 ng x min(-1) x 100 g(-1). No differences in leptin uptake were found
      between males and females or between patients with or without renal artery
      stenosis. The average renal extraction fraction of leptin was 6 +/- 2%. Renal
      leptin uptake and renal extraction fraction of leptin did not correlate with
      arterial leptin concentrations or with blood pressure, endogenous creatinine
      clearance, or the presence or absence of renal artery stenosis. In hypertensive
      patients with or without renal artery stenosis, the kidney removes only a small
      fraction of circulating leptin from the body within one passage. This fraction
      remains relatively constant despite wide variations in renal function or
      circulating leptin.

PMID- 11440919
TI  - Inhibition of salivary secretion by lipopolysaccharide: possible role of
      prostaglandins.
AB  - Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2
      (COX-2) are important in the regulation of the function of different organs
      during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6
      h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in
      submandibular glands (SMG) and blocked stimulated salivary secretion in adult
      male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine
      (AG), with LPS decreased NOS activity and PGE content. Furthermore, the
      administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in
      PGE and the production of NO. The incubation of slices of SMG in the presence of
      3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly
      significantly. The incubation of SMG in the presence of a PGE(1) analog
      (alprostadil) increased the production of NO. These results indicate that LPS
      activates NOS, leading to NO release, which activates COX, generating PGEs that
      act back to further activate NOS, causing further generation of PGEs by
      activation of COX. Because the alprostadil administration inhibited stimulated
      salivation, LPS-induced inhibition of salivation appears to be caused by
      increased PGE production. Diminished salivary secretion produces poor oral
      health; thus the use of COX-2 inhibitors to counteract the effects of inhibited
      salivation should be considered.

PMID- 11440920
TI  - Universities and tobacco money.

PMID- 11440921
TI  - Cannabinoids for pain and nausea.

PMID- 11440922
TI  - Supporting primary care with ethics advice and education.

PMID- 11440923
TI  - A national screening programme for diabetic retinopathy. Needs to learn the
      lessons of existing screening programmes.

PMID- 11440924
TI  - Taking acute stroke care seriously. In the absence of evidence we should manage
      acute stroke as a medical emergency.

PMID- 11440925
TI  - UK government urged to establish a national walking strategy.

PMID- 11440926
TI  - US consultants coach doctors in insurance fraud.

PMID- 11440927
TI  - Labour's time is "running out" over NHS, BMA leader warns.

PMID- 11440928
TI  - Germany debates embryonic stem cell research.

PMID- 11440929
TI  - UK government and doctors agree to end "blame culture".

PMID- 11440930
TI  - Hospitals must inform patients of errors.

PMID- 11440932
TI  - United Nations agrees timetable for combating AIDS.

PMID- 11440933
TI  - European Union joins fight over drug patents.

PMID- 11440934
TI  - US concedes on cheaper drug production in Brazil.

PMID- 11440935
TI  - Are cannabinoids an effective and safe treatment option in the management of
      pain? A qualitative systematic review.
AB  - OBJECTIVE: To establish whether cannabis is an effective and safe treatment
      option in the management of pain. DESIGN: Systematic review of randomised
      controlled trials. DATA SOURCES: Electronic databases Medline, Embase, Oxford
      Pain Database, and Cochrane Library; references from identified papers; hand
      searches. STUDY SELECTION: Trials of cannabis given by any route of
      administration (experimental intervention) with any analgesic or placebo (control
      intervention) in patients with acute, chronic non-malignant, or cancer pain.
      Outcomes examined were pain intensity scores, pain relief scores, and adverse
      effects. Validity of trials was assessed independently with the Oxford score.
      DATA EXTRACTION: Independent data extraction; discrepancies resolved by
      consensus. DATA SYNTHESIS: 20 randomised controlled trials were identified, 11 of
      which were excluded. Of the 9 included trials (222 patients), 5 trials related to
      cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain.
      No randomised controlled trials evaluated cannabis; all tested active substances
      were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral
      synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg
      were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg
      was less effective than codeine 60-120 mg and no better than placebo. Adverse
      effects, most often psychotropic, were common. CONCLUSION: Cannabinoids are no
      more effective than codeine in controlling pain and have depressant effects on
      the central nervous system that limit their use. Their widespread introduction
      into clinical practice for pain management is therefore undesirable. In acute
      postoperative pain they should not be used. Before cannabinoids can be considered
      for treating spasticity and neuropathic pain, further valid randomised controlled
      studies are needed.

PMID- 11440936
TI  - Cannabinoids for control of chemotherapy induced nausea and vomiting:
      quantitative systematic review.
AB  - OBJECTIVE: To quantify the antiemetic efficacy and adverse effects of cannabis
      used for sickness induced by chemotherapy. DESIGN: Systematic review. DATA
      SOURCES: Systematic search (Medline, Embase, Cochrane library, bibliographies),
      any language, to August 2000. STUDIES: 30 randomised comparisons of cannabis with
      placebo or antiemetics from which dichotomous data on efficacy and harm were
      available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol),
      and intramuscular levonantradol were tested. No cannabis was smoked. Follow up
      lasted 24 hours. RESULTS: Cannabinoids were more effective antiemetics than
      prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol,
      domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to
      1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to
      1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more
      effective in patients receiving very low or very high emetogenic chemotherapy. In
      crossover trials, patients preferred cannabinoids for future chemotherapy cycles:
      2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred
      more often with cannabinoids: "high" 10.6 (6.86 to 16.5), NNT 3; sedation or
      drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7.
      Harmful side effects also occurred more often with cannabinoids: dizziness 2.97
      (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8;
      hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20;
      and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids
      were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11.
      CONCLUSIONS: In selected patients, the cannabinoids tested in these trials may be
      useful as mood enhancing adjuvants for controlling chemotherapy related sickness.
      Potentially serious adverse effects, even when taken short term orally or
      intramuscularly, are likely to limit their widespread use.

PMID- 11440937
TI  - Hospital autopsy: standardised questionnaire survey to determine junior doctors'
      perceptions.

PMID- 11440938
TI  - Training in basic and advanced life support in UK medical schools: questionnaire
      survey.

PMID- 11440939
TI  - Drug Points: Cholestatic hepatitis in association with celecoxib.

PMID- 11440940
TI  - Referral for menstrual problems: cross sectional survey of symptoms, reasons for
      referral, and management.
AB  - OBJECTIVES: To describe the menstrual experience of women referred for menstrual
      problems, in particular menorrhagia (excessive menstrual loss), and to assess
      associations with reasons for referral given by their general practitioners, the
      women's understanding of the reasons for their attendance at the hospital
      clinics, and clinic outcome. DESIGN: Questionnaire survey, with partial review of
      case notes after 8 months. SETTING: Three hospital gynaecology clinics in Glasgow
      and Edinburgh. PARTICIPANTS: 952 women completed the questionnaire, and the first
      665 were reviewed. OUTCOME MEASURES: Reason for referral, women's reported
      menstrual problems and reason for clinic attendance, diagnosis, and treatment.
      RESULTS: Only 38% (95% confidence interval 34% to 41%) of women reported
      excessive menstrual loss as a severe problem. However 60% (57-63%) gave it as
      reason for attending a clinic, and 76% (73-79%) of general practitioners gave it
      as reason for referral. Reason for referral was significantly biased towards
      bleeding (McNemar odds ratio 4.01, 3.0 to 5.3, P<0.001) and against pain (0.54,
      0.4 to 0.7, P<0.001). Dysfunctional uterine bleeding was diagnosed in 37% (31
      42%) of the 259 women who gave as reason for attendance something other than
      bleeding. Women who were economically disadvantaged differed in prevalence of the
      main diagnoses and were more likely to fail to reattend. Hysterectomy was
      associated with referral for bleeding (relative risk 4.9, 1.6 to 15.6, P<0.001)
      but not with the patient stating bleeding as the reason for clinic attendance.
      CONCLUSIONS: Intolerance of the volume of their bleeding is not a key feature
      among women attending clinics for bleeding problems. Broad menstrual complaint
      tends to be reframed as excessive bleeding at referral and during management.
      This may result in women receiving inappropriate care. Conceptualisation and
      assessment of menorrhagia requires reconsideration.

PMID- 11440941
TI  - Progress in partnerships.

PMID- 11440943
TI  - 10-minute consultation: MMR immunisation.

PMID- 11440944
TI  - Extracts from "Clinical evidence": Bulimia nervosa.

PMID- 11440945
TI  - Lesson of the week: late diagnosis of Duchenne's muscular dystrophy presenting as
      global developmental delay.

PMID- 11440946
TI  - Improving care in accident and emergency departments.

PMID- 11440947
TI  - Systematic reviews in health care: Assessing the quality of controlled clinical
      trials.

PMID- 11440957
TI  - An updated review of the epidemiological evidence that cigarette smoking
      increases risk of colorectal cancer.
AB  - Carcinogens from tobacco reach the colorectal mucosa through either the
      alimentary tract or the circulatory system and could possibly damage or alter
      expression of important cancer-related genes. Twenty-one of 22 studies found that
      long-term, heavy cigarette smokers have a 2-3-fold elevated risk of colorectal
      adenoma. Risk of large adenomas, immediate cancer precursors, was elevated in
      smokers in 12 of 12 studies. The studies of smoking and colorectal cancer risk
      conducted earlier in the twentieth century consistently did not show any
      association. However, 27 studies in various countries, including the vast
      majority of those that have been analyzed in the past several years, now show an
      association between tobacco use and colorectal cancer. In the United States, 15
      of 16 studies conducted after 1970 in middle-age men and elderly men and, in the
      1990s, in women demonstrate an association. This temporal pattern is consistent
      with an induction period of three to four decades between genotoxic exposure and
      the diagnosis of colorectal cancer and with men as a group having begun smoking
      several decades earlier than women. Overall, accumulating evidence, much within
      the past decade, strongly supports the addition of colorectal cancer to the list
      of tobacco-associated malignancies and the possibility that up to one in five
      colorectal cancers in the United States may be potentially attributable to
      tobacco use.

PMID- 11440958
TI  - The genetic epidemiology of cancer: interpreting family and twin studies and
      their implications for molecular genetic approaches.
AB  - The recent completion of a rough draft of the human genome sequence has ushered
      in a new era of molecular genetics research into the inherited basis of a number
      of complex diseases such as cancer. At the same time, recent twin studies have
      suggested a limited role of genetic susceptibility to many neoplasms. A
      reappraisal of family and twin studies for many cancer sites suggests the
      following general conclusions: (a) all cancers are familial to approximately the
      same degree, with only a few exceptions (both high and low); (b) early age of
      diagnosis is generally associated with increased familiality; (c) familiality
      does not decrease with decreasing prevalence of the tumor-in fact, the trend is
      toward increasing familiality with decreasing prevalence; (d) a multifactorial
      (polygenic) threshold model fits the twin data for most cancers less well than
      single gene or genetic heterogeneity-type models; (e) recessive inheritance is
      less likely generally than dominant or additive models; (f) heritability
      decreases for rarer tumors only in the context of the polygenic model but not in
      the context of single-locus or heterogeneity models; (g) although the family and
      twin data do not account for gene-environment interactions or confounding, they
      are still consistent with genes contributing high attributable risks for most
      cancer sites. These results support continued search for genetic and
      environmental factors in cancer susceptibility for all tumor types. Suggestions
      are given for optimal study designs depending on the underlying architecture of
      genetic predisposition.

PMID- 11440959
TI  - The relationship between a polymorphism in CYP17 with plasma hormone levels and
      prostate cancer.
AB  - The A2 allele of the CYP17 gene has been thought to be associated with increased
      functional activity of this steroidogenic enzyme. Consequently, the A2 allele has
      been examined as a biomarker of individual susceptibility to hormone-related
      diseases among men and women. We prospectively assessed the association between
      the A2 allele of CYP17 and prostate cancer risk among 590 cases and 782 controls
      in a case-control study nested within the Physicians' Health Study cohort. We
      also evaluated associations between CYP17 genotype and plasma steroid hormones
      among controls and the potential interaction between CYP17 and SRD5A2 V89L
      polymorphisms in relationship with prostate cancer risk and circulating steroid
      hormone levels. We observed a borderline significant association between the A2
      allele and prostate cancer risk (odds ratio, 1.23; 95% confidence interval, 0.99
      1.54), however, we did not observe evidence of a gene-dosage effect (versus A1/A1
      genotype: A1/A2 genotype; odds ratio, 1.26; 95% confidence interval, 0.99-1.59;
      A2/A2 genotype: odds ratio, 1.17; 95% confidence interval, 0.85-1.61). The A2
      allele was not overrepresented among cases with advanced prostate cancer. Among
      controls, carriers of the A2 allele had steroid hormone levels similar to
      noncarriers. We also found no evidence of a gene-gene interaction between CYP17
      and SRD5A2 V89L polymorphisms on prostate cancer risk or endogenous steroid
      hormone levels. These results suggest that CYP17 genotype may possibly confer a
      small increased susceptibility to prostate cancer but is not a strong predictor
      of endogenous steroid hormone levels in men.

PMID- 11440960
TI  - Inverse associations between plasma lycopene and other carotenoids and prostate
      cancer.
AB  - Although dietary intake of tomatoes and tomato products containing lycopene has
      been reported to reduce the risk of prostate cancer, few studies have been done
      on the relationship between plasma lycopene and other carotenoids and prostate
      cancer. This case-control study was conducted to investigate the effects of
      plasma lycopene, other carotenoids, and retinol, as well as alpha- and gamma
      tocopherols on the risk of prostate cancer. The study included 65 patients with
      prostate cancer and 132 cancer-free controls; all of them were interviewed using
      a standard epidemiological questionnaire at the Memorial Sloan-Kettering Cancer
      Center from 1993 to 1997. Plasma levels of carotenoids, retinol, and tocopherols
      were measured by high performance liquid chromatography. An unconditional
      logistic regression model was used in bivariate and multivariate analyses using
      Statistical Analysis System (SAS). After adjusting for age, race, years of
      education, daily caloric intake, pack-years of smoking, alcohol consumption, and
      family history of prostate cancer, significantly inverse associations with
      prostate cancer were observed with plasma concentrations of the following
      carotenoids: lycopene [odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04
      0.78; P for trend, 0.0052] and zeaxanthin (OR, 0.22; 95% CI, 0.06-0.83; P for
      trend, 0.0028) when comparing highest with lowest quartiles. Borderline
      associations were found for lutein (OR, 0.30; 95% CI, 0.09-1.03; P for trend,
      0.0064) and beta-cryptoxanthin (OR, 0.31; 95% CI, 0.08-1.24; P for trend,
      0.0666). No obvious associations were found for alpha- and beta-carotenes,
      retinol, and alpha- and gamma-tocopherols. Our study confirmed the inverse
      associations between lycopene, other carotenoids such as zeaxanthin, lutein, and
      beta-cryptoxanthin, and prostate cancer. This study provides justification for
      further research on the associations between lycopene and other antioxidants and
      the risk of prostate cancer.

PMID- 11440961
TI  - Reliability and validity of commercially available, direct radioimmunoassays for
      measurement of blood androgens and estrogens in postmenopausal women.
AB  - In large-scale epidemiological studies on endogenous sex steroids and cancer
      risk, direct immunoassays of circulating hormone levels have the advantage of
      being fast and comparatively inexpensive while requiring only small sample
      volumes. On the other hand, indirect assays after organic extraction and
      chromatographic prepurification have the advantage of reducing specific
      interferences and matrix effects and hence are thought to have better validity.
      We compared direct assays of testosterone (T, six different assays), Delta4
      androstenedione (A, four assays), estrone (E(1), one assay), and 17beta-estradiol
      (E(2), five assays) with measurements obtained by an indirect assay in a
      representative subset of 20 postmenopausal women who were part of a large
      prospective cohort study. Within-batch reproducibilities of the subject rankings
      by relative hormone levels were good (intraclass correlations >0.89) for all
      direct assays tested. Between batches, reproducibilities generally were also
      acceptable (r > 0.80) to good (r > 0.90) in terms of Pearson's correlations. The
      between-batch reproducibility in terms of intraclass correlations was
      systematically lower in terms of Pearson's correlations, however, because of
      between-batch variations in the absolute scale of measurements. The relative
      validity of direct versus indirect assays in terms of the subjects' ranking by
      relative hormone levels was also high for most of the kits tested for T, A, and
      E(1) (Pearson's correlations between 0.70 and 0.89) but was high for only two
      kits of five tested for E(2) (correlations of 0.86 and 0.84). On an absolute
      scale, mean measurement values were generally higher for direct assays than for
      the indirect assay and, for each hormone, varied substantially, depending on the
      kit used. Overall, the results of this study show that, with careful selection,
      commercial kits for direct radioimmunoassays of steroid hormones in
      postmenopausal serum can be found that may allow a reliable estimation of
      relative risks in epidemiological studies. However, standardization of the
      absolute scale of assays remains problematic.

PMID- 11440962
TI  - Prediagnostic levels of serum beta-cryptoxanthin and retinol predict smoking
      related lung cancer risk in Shanghai, China.
AB  - Higher blood levels of beta-carotene have been found to be associated with
      reduced risk of lung cancer, but large intervention trials have failed to
      demonstrate reduced lung cancer incidence after prolonged high-dose beta-carotene
      supplementation. Data on blood levels of specific carotenoids other than beta
      carotene in relation to lung cancer are scarce. Little is known about the
      relationship between prediagnostic serum levels of carotenoids, retinol, and
      tocopherols, and risk of lung cancer especially in non-Western populations.
      Between January 1986 and September 1989, 18,244 men ages 45-64 years participated
      in a prospective study of diet and cancer in Shanghai, China. Information on
      tobacco smoking and other lifestyle factors was obtained through in-person
      interviews. A serum sample was collected from each study participant at baseline.
      During the first 12 years of follow-up, 209 lung cancer cases, excluding those
      diagnosed within 2 years of enrollment, were identified. For each cancer case,
      three cancer-free control subjects were randomly selected from the cohort and
      matched to the index case by age (within 2 years), month and year of blood sample
      collection, and neighborhood of residence. Serum concentrations of retinol, alpha
      and gamma-tocopherols, and specific carotenoids including alpha-carotene, beta
      carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were determined on
      the 209 cases and 622 matched controls by high-performance liquid chromatography
      methods. A high prediagnostic serum level of beta-cryptoxanthin was significantly
      associated with reduced risk of lung cancer; relative to the lowest quartile, the
      smoking-adjusted relative risks (95% confidence intervals) for the 2nd, 3rd, and
      4th quartile categories were 0.72 (0.41-1.26), 0.42 (0.21-0.84), and 0.45 (0.22
      0.92), respectively (P for trend = 0.02). Increased serum levels of other
      specific carotenoids including alpha-carotene, beta-carotene, lycopene, and
      lutein/zeaxanthin were related to reduced risk of lung cancer although the
      inverse associations were no longer statistically significant after adjustment
      for smoking. A statistically significant 37% reduction in risk of lung cancer was
      noted in smokers with above versus below median level of total carotenoids. Serum
      retinol levels showed a threshold effect on lung cancer risk. Compared with the
      lowest quartile (<40 microg/dl), the smoking-adjusted relative risk (95%
      confidence interval) was 0.60 (0.39-0.92) for men in the 2nd-4th quartiles of
      retinol values combined; no additional decrease in risk was observed between
      individuals from the 2nd to 4th quartiles. There were no associations between
      prediagnostic serum levels of alpha- and gamma-tocopherols and lung cancer (all
      Ps for trend > or =0.4). The present data indicate that higher prediagnostic
      serum levels of total carotenoids and beta-cryptoxanthin were associated with
      lower smoking-related lung cancer risk in middle-aged and older men in Shanghai,
      China. Low level of serum retinol (with a threshold effect) is associated with
      increased lung cancer risk in this oriental population.

PMID- 11440963
TI  - Oltipraz chemoprevention trial in Qidong, People's Republic of China: results of
      urine genotoxicity assays as related to smoking habits.
AB  - A Phase II chemoprevention trial was carried out in Qidong, Jiangsu Province,
      People's Republic of China. The recruited subjects, all of whom were positive for
      serum aflatoxin-albumin adducts, were divided into three treatment arms: placebo;
      oltipraz ([5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione]) given daily at 125 mg
      p.o.; and oltipraz given once per week at 500 mg p.o. Besides biomarkers related
      to aflatoxin B(1) exposure, the genotoxicity of blind-coded urine XAD-2
      concentrates was evaluated in 201 subjects on the fifth and seventh week of
      intervention. Genotoxicity was assessed both in the Ames reversion test in strain
      YG1024 of Salmonella typhimurium, in the presence of an exogenous metabolic
      system (S9 mix), with or without beta-glucuronidase, and in a DNA repair test in
      Escherichia coli. Heating of concentrated urine samples or of cigarette smoke
      condensates was discovered to result in a significant enhancement of their
      mutagenicity. It was also found that the mutagenicity of condensates from the
      most extensively used brands of cigarettes in Qidong was much lower than that of
      Western cigarette brands. Urine mutagenicity was unrelated to treatment with
      oltipraz, intervention time, gender, and supplement of S9 mix with beta
      glucuronidase. Mutagenicity was significantly but variably higher in cigarette
      smokers than in nonsmokers, which suggests that the urinary excretion of mutagens
      in the examined population was not exclusively attributable to smoking.
      Nevertheless, within smokers (28% of the recruited subjects; 67% of all males),
      the mutagenic potency was significantly correlated with the self-reported number
      of cigarettes smoked per day and, even more sharply, with the cotinine
      concentrations in urines. In conclusion, this study demonstrated the validity of
      urine mutagenicity assays as a biomarker of tobacco smoke exposure that can be
      investigated on a relatively large scale in chemoprevention trials and provided
      evidence that oltipraz treatment had no influence on this parameter in the
      examined population.

PMID- 11440964
TI  - Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal
      epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma.
AB  - Exposure to aflatoxins is a risk factor for hepatocellular carcinoma (HCC).
      Aflatoxins occur in peanut butter and are metabolized by genetically polymorphic
      enzymes such as glutathione-S-transferases encoded by glutathione-S-transferase
      mu 1 gene (GSTM1) and glutathione-S-transferase theta 1 gene (GSTT1) and
      microsomal epoxide hydrolase encoded by epoxide hydrolase gene (EPHX). The rate
      at which aflatoxins become activated or detoxified may depend on polymorphisms in
      the encoding genes. GSTM1 homozygous deletion was indeed found to modify the
      association between peanut butter consumption and HCC. In this study, we
      investigate possible roles of GSTT1 and EPHX polymorphisms in this relationship.
      From a Sudanese case-control study on HCC, we analyzed data of 112 incident cases
      and 194 controls. All participants were interviewed using a standardized
      questionnaire inquiring about social and demographic factors, peanut butter
      consumption, and other known HCC risk factors. Univariate analysis showed that
      GSTT1 polymorphism was not associated with HCC, whereas EPHX 113HH and 139HH
      genotypes increased the risk of HCC (Odds ratio, 3.10; 95% Confidence interval,
      1.18-8.12). Adjustment for age and region of origin slightly attenuated this
      association (Odds ratio, 2.56; 95% Confidence interval, 0.83-7.95).
      Interestingly, unlike GSTM1, both GSTT1 and EPHX polymorphism did not modify the
      association between peanut butter consumption and HCC. In conclusion, these
      epidemiological findings do not suggest significant roles of GSTT1 and EPHX in
      aflatoxin metabolism, although EPHX polymorphism is possibly related to the
      increased risk of HCC. Further studies are needed to investigate mechanisms by
      which the EPHX polymorphism potentially modifies cancer risk.

PMID- 11440965
TI  - Second primary cancers after sporadic and familial colorectal cancer.
AB  - Second cancers were studied among 68,104 cases of colorectal cancer (CRC) from
      the Swedish Family-Cancer Database. A total of 1,113 patients received a
      diagnosis of second CRC; 25 of them had a family history of CRC. Cases of second
      CRC with a family history were diagnosed up to 10 years before sporadic cases.
      The relative risk (RR) of all second CRCs was 2.21 compared with the first CRC.
      Familial second CRCs had a 2-fold risk compared with the sporadic forms. Age of
      onset was the most important covariate of second CRCs; the relative risk at ages
      15-39 years was 27 compared with the first CRC. Familial CRC was associated with
      a high risk of small-intestinal, endometrial, and gastric cancers apart from CRC,
      all typical of hereditary nonpolyposis CRC (HNPCC). Among familial cases, 36% of
      second CRCs and 100% of endometrial cancers came from families that fulfilled the
      Bethesda criteria for HNPCC. Only 12 families conformed to the Amsterdam
      criteria; in family members, the risk of second CRC was 127-fold and that of
      endometrial cancer 257-fold. Other sites that were in excess among all second
      cancers were many cancers linked to HNPCC and, additionally, breast, prostate,
      thyroid and other endocrine, skin, and genital cancers. The high risk of second
      cancer after early-onset CRC calls for evaluation of family history and clinical
      surveillance.

PMID- 11440966
TI  - Mismatch repair deficiency and CpG island hypermethylation in sporadic colon
      adenocarcinomas.
AB  - Many studies have documented CpG island hypermethylation in human colon
      adenocarcinomas. Several of these reports have additionally found such CpG island
      hypermethylation to be more extensive in tumors with a mismatch-repair
      deficiency, as revealed by microsatellite instability (MSI+). Because the source
      of samples used in these prior studies may not have been representative of the
      general population, we have reinvestigated this issue using samples from a
      population-based study. A total of 15 MSI+ tumors were identified, and they were
      compared with 47 MSI- tumors that were similar in distribution by age, sex, and
      race. Microdissected tumor and normal adjacent mucosal DNA samples from each
      patient were subjected to a quantitative DNA methylation analysis at 13 separate
      CpG dinucleotides located in five CpG islands in four different genes [APC, ESR1
      (ER), CDKN2A (p16; promoter and exon 2), and MLH1]. Four of five CpG islands
      showed a statistically significantly increased level of methylation in tumor
      tissue compared with adjacent normal mucosa. In contrast to previous studies, we
      did not find any statistically significant correlations between MSI status and
      methylation levels of any of the CpG islands other than MLH1. Furthermore, we
      observed a positive correlation between MLH1 methylation and CDKN2A methylation
      (P = 0.03), whereas no association was noted between MSI positivity and CDKN2A
      methylation (P = 0.95). The latter results suggest a possible defect in the
      protection against CpG island hypermethylation shared between CDKN2A and MLH1 and
      do not support the notion of a functional association between CDKN2A methylation
      and the phenotype of mismatch repair deficiency.

PMID- 11440967
TI  - Long-term recreational physical activity and breast cancer in the National Health
      and Nutrition Examination Survey I epidemiologic follow-up study.
AB  - Our purpose was to study the association between long-term recreational physical
      activity and breast cancer in the Epidemiological Follow-up Study (NHEFS) of the
      first National Health and Nutrition Examination Survey (NHANES I, 1971-1975). The
      analytic cohort included 6160 women who were free of breast cancer at the first
      NHEFS follow-up in 1982-1984 and had interview data on recreational physical
      activity (low, moderate, and high) in 1982-1984 and 10 years earlier, in 1971
      1975. We created categories of long-term (1982-1984 + 1971-1975) recreational
      physical activity: (a) consistently low; (b) moderate/inconsistent; and (c)
      consistently high. Data were analyzed using Cox proportional hazard regression
      models. A total of 138 women developed breast cancer between 1982-1984 and 1992.
      In women > or =50 years of age in 1982-1984, consistently high (versus
      consistently low) recreational physical activity was associated with a 67%
      reduction in breast cancer risk (n = 96 cases; relative risk, 0.33; 95%
      confidence interval, 0.14-0.82; P for trend = 0.03); in women <50 years of age (n
      = 42 cases), there was no association. Associations were not modified by body
      mass index or by weight gain as an adult. High recreational physical activity
      over the long-term may reduce breast cancer risk in women > or =50 years of age;
      in this sample, it did so regardless of weight history.

PMID- 11440968
TI  - Fas/APO-1 promoter polymorphism is not associated with non-melanoma skin cancer.

PMID- 11440969
TI  - Tissue factor, the emerging link between inflammation, thrombosis, and vascular
      remodeling.

PMID- 11440970
TI  - On genetics of dilated cardiomyopathy and transgenic models: all is not crystal
      clear in myopathic hearts.

PMID- 11440971
TI  - Cardiovascular defects associated with abnormalities in midline development in
      the Loop-tail mouse mutant.
AB  - Loop-tail (Lp) is a naturally occurring mouse mutant that develops severe neural
      tube defects. In this study, we describe complex cardiovascular defects in Lp
      homozygotes, which include double-outlet right ventricle, with obligatory
      perimembranous ventricular septal defects, and double-sided aortic arch, with
      associated abnormalities in the aortic arch arteries. Outflow tract and aortic
      arch defects are often related to abnormalities in the cardiac neural crest, but
      using molecular and anatomic markers, we show that neural crest migration is
      normal in Lp/Lp embryos. On the other hand, the heart fails to loop normally in
      Lp/Lp embryos, in association with incomplete axial rotation and reduced cervical
      flexion. As a consequence, the ventricular loop is shifted posteromedially
      relative to its position in wild-type embryos. This suggests that the observed
      cardiac alignment defects in the Lp mutant may be secondary to failure of neural
      tube closure and incomplete axial rotation. Double-sided aortic arch is a rare
      finding among mouse models. In humans, it is usually an isolated malformation,
      only rarely occurring in combination with other cardiac defects. We suggest that
      the double-sided arch arises as a primary defect in the Lp mutant, unrelated to
      the alignment defects, perhaps reflecting a role for the (as-yet-unknown) Lp gene
      in maintenance/regression of the aortic arch system.

PMID- 11440972
TI  - Phosphatidylinositol 3-kinase/Akt signaling controls endothelial cell sensitivity
      to Fas-mediated apoptosis via regulation of FLICE-inhibitory protein (FLIP).
AB  - Fas is constitutively expressed on endothelial cells, but in contrast to smooth
      muscle and other cell types, endothelial cells are highly resistant to Fas
      mediated apoptosis. In this study, we examined the role of the serine/threonine
      kinase Akt/PKB in controlling the sensitivity of endothelial cells to Fas
      mediated apoptosis. Serum deprivation inhibited expression of the caspase-8
      inhibitor FLICE-inhibitory protein (FLIP), which functions downstream from Fas.
      FLIP expression levels were restored when serum-depleted cells were treated with
      vascular endothelial growth factor. Treatment with the phosphatidylinositol 3
      kinase (PI 3-kinase) inhibitors wortmannin or LY294002 or infection of the
      adenoviral construct expressing dominant-negative Akt (Adeno-dnAkt) also
      inhibited the expression of FLIP in endothelial cells, whereas the MEK inhibitor
      PD98059 had no effect. Conversely, adenovirus-mediated transfection of a
      constitutively-active Akt gene abolished the wortmannin- and LY294002-mediated
      downregulation of FLIP. Suppression of PI 3-kinase signaling sensitized
      endothelial cells to Fas-mediated apoptosis. Under conditions of suppressed PI 3
      kinase signaling, restoration of FLIP expression reversed the induced sensitivity
      of endothelial cells to Fas-mediated apoptosis. These data suggest that
      inhibition of Fas-mediated apoptosis, via promotion of FLIP expression, is a
      mechanism through which Akt signaling can promote endothelial cell survival.

PMID- 11440973
TI  - Temporally regulated and tissue-specific gene manipulations in the adult and
      embryonic heart using a tamoxifen-inducible Cre protein.
AB  - The advent of conditional and tissue-specific recombination systems in gene
      targeted or transgenic mice has permitted an assessment of single gene function
      in a temporally regulated and cell-specific manner. Here we generated transgenic
      mice expressing a tamoxifen-inducible Cre recombinase protein fused to two mutant
      estrogen-receptor ligand-binding domains (MerCreMer) under the control of the
      alpha-myosin heavy chain promoter. These transgenic mice were crossed with the
      ROSA26 lacZ-flox-targeted mice to examine Cre recombinase activity and the
      fidelity of the system. The data demonstrate essentially no Cre-mediated
      recombination in the embryonic, neonatal, or adult heart in the absence of
      inducing agent but >80% recombination after only four tamoxifen injections.
      Expression of the MerCreMer fusion protein within the adult heart did not affect
      cardiac performance, cellular architecture, or expression of hypertrophic marker
      genes, demonstrating that the transgene-encoded protein is relatively innocuous.
      In summary, MerCreMer transgenic mice represent a tool for temporally regulated
      inactivation of any loxP-targeted gene within the developing and adult heart or
      for specifically directing recombination and expression of a loxP-inactivated
      cardiac transgene in the heart.

PMID- 11440974
TI  - Tumor necrosis factor-alpha induces fibronectin synthesis in coronary artery
      smooth muscle cells by a nitric oxide-dependent posttranscriptional mechanism.
AB  - Postcardiac transplant coronary arteriopathy is associated with tumor necrosis
      factor-alpha (TNF-alpha) induction of fibronectin-dependent smooth muscle cell
      (SMC) migration into the subendothelium, resulting in occlusive neointimal
      formation. Because expression of inducible nitric oxide synthase (iNOS) is
      elevated in neointimal formation after transplantation and upregulated in
      vascular SMCs by TNF-alpha, we investigated whether TNF-alpha induction of
      fibronectin synthesis in coronary artery (CA) SMCs is mediated by nitric oxide
      (NO). TNF-alpha caused a dose-dependent increase in reactive oxygen and nitrogen
      intermediates in CA SMCs (P<0.05). This correlated with increased NO production
      (P<0.05) and fibronectin synthesis (P<0.05). TNF-alpha induction of fibronectin
      synthesis was abrogated by the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA)
      (P<0.05) or the flavonoid-containing enzyme inhibitor diphenyleneiodonium (DPI)
      (P<0.05) and reproduced with the NO donor S-nitroso-N-acetyl-penicillamine (SNAP)
      (P<0.05). Northern blotting showed no effect of TNF-alpha on steady-state
      fibronectin mRNA levels. TNF-alpha increased expression of light chain 3 (LC-3),
      a protein shown previously to facilitate fibronectin mRNA translation through its
      interaction with an adenosine-uracil rich element (ARE) in the 3'-untranslated
      region of fibronectin mRNA. RNA gel mobility shift and UV cross-linking assays
      using CA SMC lysates revealed protein binding complexes with radiolabeled
      oligonucleotide containing the ARE, similar to those generated with recombinant
      LC-3. One of these complexes increased after TNF-alpha treatment, an effect
      inhibited with L-NMMA or DPI. These data demonstrate a novel paradigm whereby
      cytokines regulate mRNA translation of extracellular matrix proteins through NO
      dependent modulation of RNA binding protein interaction with mRNA.

PMID- 11440975
TI  - Molecular interactions between two long-QT syndrome gene products, HERG and
      KCNE2, rationalized by in vitro and in silico analysis.
AB  - The cardiac delayed rectifier potassium current mediates repolarization of the
      action potential and underlies the QT interval of the ECG. Mutations in either of
      the two molecular components of the rapid delayed rectifier (I(K,r)), HERG and
      KCNE2, have been linked to heritable or acquired long-QT syndrome. Mechanisms
      whereby mutations of KCNE2 produce fatal cardiac arrhythmias characteristic of
      long-QT syndrome remain unclear. In this study, we characterize functional
      interactions between HERG and KCNE2 with a view to defining underlying mechanisms
      for action potential prolongation and long-QT syndrome. Whereas coexpression of
      hKCNE2 with HERG alters both kinetics and density of ionic current, incorporation
      of these effects into a quantitative model of the action potential predicts that
      only changes in current density significantly affect repolarization. Thus, the
      primary functional consequence of hKCNE2 on action potential morphology is
      through modulation of I(K,r) density, as predicted by the model. Mutations
      associated with long-QT syndrome that result only in modest changes of gating
      kinetics may be epiphenomena or may modulate action potential repolarization via
      interaction with alternative pore-forming potassium channel alpha subunits.

PMID- 11440976
TI  - Redox regulation of vascular smooth muscle cell differentiation.
AB  - Experiments were performed to determine the role of reactive oxygen species (ROS)
      in regulating vascular smooth muscle cell (VSMC) phenotype. After quiescence,
      cultured human VSMCs increased their expression of differentiation proteins
      (alpha-actin, calponin, and SM1 and SM2 myosin), but not beta-actin. ROS
      activity, determined using the H(2)O(2)-sensitive probe
      dichlorodihydrofluorescein (DCF), remained high in quiescent cells and was
      inhibited by catalase (3000 U/mL) or by N-acetylcysteine (NAC, 2 to 20 mmol/L). A
      superoxide dismutase mimic (SOD; MnTMPyP, 25 micromol/L) or SOD plus low
      concentrations of NAC (SODNAC2, 2 mmol/L) increased DCF fluorescence, which was
      inhibited by catalase or by NAC (10 to 20 mmol/L). Inhibition of ROS activity (by
      catalase or NAC) decreased the baseline expression of differentiation proteins,
      whereas elevation of ROS (by SOD or SODNAC2) increased expression of the
      differentiation markers. The latter effect was blocked by catalase or by NAC (10
      to 20 mmol/L). None of the treatments altered beta-actin expression. SODNAC2
      treated cells demonstrated contractions to endothelin that were absent in
      proliferating cells. p38 Mitogen-activated protein kinase (MAPK) activity was
      decreased when ROS activity was reduced (NAC, 10 mmol/L) and was augmented when
      ROS activity was increased (SODNAC2). Inhibition of p38 MAPK with pyridyl
      imidazole compound (SB202190, 2 to 10 micromol/L) reduced expression of
      differentiation proteins occurring under basal conditions and in response to
      SODNAC2. Transduction of VSMCs with an adenovirus encoding constitutively active
      MKK6, an activator of p38 MAPK, increased expression of differentiation proteins,
      whereas transduction with an adenovirus encoding dominant-negative p38 MAPK
      decreased expression of the differentiation proteins. These findings demonstrate
      that ROS can increase VSMC differentiation through a p38 MAPK-dependent pathway.

PMID- 11440977
TI  - Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular
      smooth muscle cells: Role of the p22(phox)-containing NADPH oxidase.
AB  - The heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) is
      activated under hypoxic conditions, resulting in the upregulation of its target
      genes plasminogen activator inhibitor-1 (PAI-1) and vascular endothelial growth
      factor (VEGF). PAI-1 and VEGF are also induced in response to vascular injury,
      which is characterized by the activation of platelets and the coagulation cascade
      as well as the generation of reactive oxygen species (ROS). However, it is not
      known whether HIF-1 is also stimulated by thrombotic factors. We investigated the
      role of thrombin, platelet-associated growth factors, and ROS derived from the
      p22(phox)-containing NADPH oxidase in the activation of HIF-1 and the induction
      of its target genes PAI-1 and VEGF in human vascular smooth muscle cells (VSMCs).
      Thrombin, platelet-derived growth factor-AB (PDGF-AB), and transforming growth
      factor-beta(1) (TGF-beta(1)) upregulated HIF-1alpha protein in cultured and
      native VSMCs. This response was accompanied by nuclear accumulation of HIF-1alpha
      as well as by increased HIF-1 DNA-binding and reporter gene activity. The
      thrombin-induced expression of HIF-1alpha, PAI-1, and VEGF was attenuated by
      antioxidant treatment as well as by transfection of p22(phox) antisense
      oligonucleotides. Inhibition of p38 mitogen-activated protein kinase and
      phosphatidylinositol-3-kinase significantly decreased thrombin-induced HIF
      1alpha, PAI-1, and VEGF expression. These findings demonstrate that the HIF-1
      signaling pathway can be stimulated by thrombin and platelet-associated growth
      factors and that a redox-sensitive cascade activated by ROS derived from the
      p22(phox)-containing NADPH oxidase is crucially involved in this response.

PMID- 11440978
TI  - Vascular smooth muscle cell-directed overexpression of heme oxygenase-1 elevates
      blood pressure through attenuation of nitric oxide-induced vasodilation in mice.
AB  - To elucidate pathophysiological roles of heme oxygenase (HO)-1 in regulation of
      vascular tone in vivo, we have developed and characterized transgenic (Tg) mice
      that overexpress HO-1 site specifically in vascular smooth muscle cells (VSMCs).
      The Tg mice were generated by use of human HO-1 cDNA under the control of SM22
      alpha promoter. The HO-1 gene overexpression was demonstrated by Northern blot
      analysis and coincided with increases in the protein expression in VSMCs and
      total HO activities. Tg mice exhibited a significant increase in arterial
      pressure at various ages and displayed impaired nitrovasodilatory responses in
      isolated aortic segments versus nontransgenic littermates while enhancing their
      nitric oxide (NO) production. The pressure of Tg mice was unchanged by systemic
      administration of either N(omega)-nitro-L-arginine or SNP. Furthermore, the
      isolated aorta in these mice exhibited lesser extents of NO-elicited cGMP
      elevation via soluble guanylate cyclase (sGC), while exhibiting no notable
      downregulation of sGC expression. Such impairment of the NO-elicited cGMP
      increase was restored significantly by tin protoporphyrin IX, an HO inhibitor. On
      the other hand, 3-(5'-hydroxymethyl-2' furyl)-1-benzyl-indazol (YC-1), an NO
      independent activator of sGC, increased cGMP and relaxed aortas from Tg mice to
      levels comparable with those from nontransgenic mice, which indicates that
      contents of functionally intact sGC are unlikely to differ between the two
      systems. These findings suggest that site-specific overexpression of HO-1 in
      VSMCs suppresses vasodilatory response to NO and thereby leads to an elevation of
      arterial pressure.

PMID- 11440979
TI  - Adrenomedullin induces endothelium-dependent vasorelaxation via the
      phosphatidylinositol 3-kinase/Akt-dependent pathway in rat aorta.
AB  - To study the mechanisms by which adrenomedullin (AM) induces endothelium
      dependent vasorelaxation, we examined whether AM-induced endothelium-dependent
      vasodilation was mediated by the phosphatidylinositol 3-kinase (PI3K)/Akt
      dependent pathway in rat aorta, because it was recently reported that PI3K/Akt
      was implicated in the activation of endothelial NO synthase. AM-induced
      vasorelaxation in thoracic aorta with intact endothelium was inhibited by
      pretreatment with PI3K inhibitors to the same level as that in endothelium
      denuded aorta. AM elicited Akt phosphorylation in a time- and dose-dependent
      manner. AM-induced Akt phosphorylation was inhibited by pretreatment with a
      calmodulin-dependent protein kinase inhibitor as well as with PI3K inhibitors.
      When an adenovirus construct expressing a dominant-negative Akt mutant (Ad/dnAkt)
      was injected into abdominal aortas so that the mutant was expressed predominantly
      in the endothelium layer, AM-induced vasodilation was diminished to the same
      level as that in endothelium-denuded aortas. Finally, AM-induced cGMP production,
      which was used as an indicator for NO production, was suppressed by PI3K
      inhibition or by Ad/dnAkt infection into the endothelium. These results suggested
      that AM induced Akt activation in the endothelium via the Ca(2+)/calmodulin
      dependent pathway and that this was implicated in the production of NO, which in
      turn induced endothelium-dependent vasodilation in rat aorta.

PMID- 11440980
TI  - Role for tissue factor pathway in murine model of vascular remodeling.
AB  - Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the
      extrinsic clotting cascade and is considered a major regulator of arterial
      thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor
      of TF-initiated coagulation. The aim of this study was to define the complex
      interplay between TF and TFPI and the regulation of vascular thrombogenicity in a
      model of vascular remodeling. To determine the levels and pattern of vascular
      expression of TF and TFPI associated with vascular remodeling, a murine model of
      flow cessation was studied. TF activity of the arteries increased after ligation
      (P<0.05). Quantitative analysis of homogenates of remodeled carotid arteries
      revealed increased TF expression but unchanged TFPI expression compared with
      normal carotid arteries, resulting in enhanced TF activity. To determine the
      potential therapeutic role of TFPI in this thrombogenic state, mice were treated
      with intravascular adenoviral delivery of either murine TFPI (Ad-mTFPImyc) or a
      control adenovirus (Ad-DeltaE1). Overexpression of TFPI decreased vascular TF
      activity compared with viral control (P<0.01). Overexpression of TFPI inhibited
      neointimal formation (P=0.038), resulting in enhanced luminal area (P=0.001) 4
      weeks after flow cessation. In this murine model of vascular remodeling, an
      imbalance between TF and TFPI expression is generated, resulting in increased TF
      activity. Overexpression of TFPI in this model inhibits vascular TF activity and
      results in attenuation of vascular remodeling associated with flow interruption.

PMID- 11440981
TI  - Cyclic ADP-ribose is the primary trigger for hypoxic pulmonary vasoconstriction
      in the rat lung in situ.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary arteries, and it
      aids ventilation/perfusion matching. However, in diseases such as emphysema, HPV
      can promote hypoxic pulmonary hypertension. We recently showed that hypoxia
      constricts pulmonary arteries in part by increasing cyclic ADP-ribose (cADPR)
      accumulation in the smooth muscle and, thereby, Ca(2+) release by ryanodine
      receptors. We now report on the role of cADPR in HPV in isolated rat pulmonary
      arteries and in the rat lung in situ. In isolated pulmonary arteries, the
      membrane-permeant cADPR antagonist, 8-bromo-cADPR, blocked sustained HPV by
      blocking Ca(2+) release from smooth muscle ryanodine-sensitive stores in the
      sarcoplasmic reticulum. Most importantly, we showed that 8-bromo-cADPR blocks HPV
      induced by alveolar hypoxia in the ventilated rat lung in situ. Inhibition of HPV
      was achieved without affecting (1) constriction by membrane depolarization and
      voltage-gated Ca(2+) influx, (2) the release (by hypoxia) of an endothelium
      derived vasoconstrictor, or (3) endothelium-dependent vasoconstriction. Our
      findings suggest that HPV is both triggered and maintained by cADPR in the rat
      lung in situ.

PMID- 11440982
TI  - Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB
      crystallin aggregation and cardiomyopathy in mice.
AB  - Upregulation of alphaB-crystallin (CryAB), a small heat shock protein, is
      associated with a variety of diseases, including the desmin-related myopathies.
      CryAB, which binds to both desmin and cytoplasmic actin, may participate as a
      chaperone in intermediate filament formation and maintenance, but the
      physiological consequences of CryAB upregulation are unknown. A mutation in
      CryAB, R120G, has been linked to a familial desminopathy. However, it is unclear
      whether the mutation is directly causative. We created multiple transgenic mouse
      lines that overexpressed either murine wild-type CryAB or the R120G mutation in
      cardiomyocytes. Overexpression of wild-type CryAB was relatively benign, with no
      increases in mortality and no induction of desmin-related cardiomyopathy even in
      a line in which CryAB mRNA expression was increased approximately 104-fold and
      the protein level increased by 11-fold. In contrast, lines expressing the R120G
      mutation were compromised, with a high-expressing line exhibiting 100% mortality
      by early adulthood. Modest expression levels resulted in a phenotype that was
      strikingly similar to that observed for the desmin-related cardiomyopathies. The
      desmin filaments in the cardiomyocytes were overtly affected, myofibril alignment
      was significantly impaired, and a hypertrophic response occurred at both the
      molecular and cellular levels. The data show that the R120G mutation causes a
      desminopathy, is dominant negative, and results in cardiac hypertrophy.

PMID- 11440983
TI  - Increased expression of protease-activated receptor-2 (PAR2) and PAR4 in human
      coronary artery by inflammatory stimuli unveils endothelium-dependent relaxations
      to PAR2 and PAR4 agonists.
AB  - Protease-activated receptor (PAR)1 and PAR2 are expressed on vascular endothelial
      cells and mediate endothelium-dependent relaxation in several species, and PAR4
      agonists cause similar responses in rat aortas. To date, only PAR1 has been
      reported to mediate relaxation of human arteries despite endothelial cell
      expression of both PAR1 and PAR2 in these tissues. Because inflammatory stimuli
      increase PAR2 expression in human endothelial cells in culture, the present study
      investigated the effect of similar stimuli on PARs in human isolated coronary
      arteries (HCAs). In HCA ring segments suspended for isometric tension
      measurements, the selective PAR1-activating peptide, TFLLR (0.01 to 10
      micromol/L), caused endothelium-dependent relaxation of precontracted
      preparations. Little or no change in vascular tension was elicited by either the
      PAR2- or PAR4-activating peptides, SLIGKV and GYPGQV, respectively (up to 100
      micromol/L). Exposure of HCAs to interleukin (IL)-1alpha (1 ng/mL, 12 hours) or
      tumor necrosis factor-alpha (3 nmol/L, 12 hours) did not affect PAR1 expression
      but increased PAR2 and PAR4 mRNA levels by approximately 5- and 4-fold,
      respectively, as determined by quantitative polymerase chain reaction. Similar IL
      1alpha treatment did not affect TFLLR-induced relaxations but revealed
      significant endothelium-dependent relaxations to SLIGKV (100 micromol/L, 61.4+/
      6.7%) and GYPGQV (100 micromol/L, 34.8+/-6.4%). These studies are the first to
      demonstrate functional PAR2 and PAR4 in human arteries in situ. The selective
      upregulation of PAR2 and PAR4 expression and the increased vascular response in
      HCAs after exposure to inflammatory stimuli suggest a role for these endothelial
      receptors during inflammation.

PMID- 11440984
TI  - Number and migratory activity of circulating endothelial progenitor cells
      inversely correlate with risk factors for coronary artery disease.
AB  - Recent studies provide increasing evidence that postnatal neovascularization
      involves bone marrow-derived circulating endothelial progenitor cells (EPCs). The
      regulation of EPCs in patients with coronary artery disease (CAD) is unclear at
      present. Therefore, we determined the number and functional activity of EPCs in
      45 patients with CAD and 15 healthy volunteers. The numbers of isolated EPCs and
      circulating CD34/kinase insert domain receptor (KDR)-positive precursor cells
      were significantly reduced in patients with CAD by approximately 40% and 48%,
      respectively. To determine the influence of atherosclerotic risk factors, a risk
      factor score including age, sex, hypertension, diabetes, smoking, positive family
      history of CAD, and LDL cholesterol levels was used. The number of risk factors
      was significantly correlated with a reduction of EPC levels (R=-0.394, P=0.002)
      and CD34-/KDR-positive cells (R=-0.537, P<0.001). Analysis of the individual risk
      factors demonstrated that smokers had significantly reduced levels of EPCs
      (P<0.001) and CD34-/KDR-positive cells (P=0.003). Moreover, a positive family
      history of CAD was associated with reduced CD34-/KDR-positive cells (P=0.011).
      Most importantly, EPCs isolated from patients with CAD also revealed an impaired
      migratory response, which was inversely correlated with the number of risk
      factors (R=-0.484, P=0.002). By multivariate analysis, hypertension was
      identified as a major independent predictor for impaired EPC migration (P=0.043).
      The present study demonstrates that patients with CAD revealed reduced levels and
      functional impairment of EPCs, which correlated with risk factors for CAD. Given
      the important role of EPCs for neovascularization of ischemic tissue, the
      decrease of EPC numbers and activity may contribute to impaired vascularization
      in patients with CAD. The full text of this article is available at
      http://www.circresaha.org.

PMID- 11440985
TI  - HCN2 overexpression in newborn and adult ventricular myocytes: distinct effects
      on gating and excitability.
AB  - Ventricular pacemaker current (I(f)) shows distinct voltage dependence as a
      function of age, activating outside the physiological range in normal adult
      ventricle, but less negatively in neonatal ventricle. However, heterologously
      expressed HCN2 and HCN4, the putative molecular correlates of ventricular I(f),
      exhibit only a modest difference in activation voltage. We therefore prepared an
      adenoviral construct (AdHCN2) of HCN2, the dominant ventricular isoform at either
      age, and used it to infect neonatal and adult rat ventricular myocytes to
      investigate the role of maturation on current gating. The expressed current
      exhibited an 18-mV difference in activation (V(1/2) -95.9+/-1.9 in adult; -77.6+/
      1.6 mV in neonate), comparable to the 22-mV difference between native I(f) in
      adult and neonatal cultures (V(1/2) -98.7 versus -77.0 mV). This did not result
      from developmental differences in basal cAMP, because saturating cAMP in the
      pipette caused an equivalent positive shift in both preparations. In the neonate,
      AdHCN2 caused a significant increase in spontaneous rate compared with control
      (88+/-5 versus 48+/-4 bpm). In adult, where HCN2 activates more negatively, the
      effect was evident only during anodal excitation, requiring significantly less
      stimulus energy than control (2149+/-266 versus 3140+/-279 mV. ms). Thus,
      ventricular maturational state influences the voltage dependence of expressed
      HCN2, resulting in distinct physiological impact of expressed channels in neonate
      and adult myocytes. The full text of this article is available at
      http://www.circresaha.org.

PMID- 11440986
TI  - Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in
      different species: implications for the evolution of functional redundancy.
AB  - The alpha-actinins are a multigene family of four actin-binding proteins related
      to dystrophin. The two skeletal muscle isoforms of alpha-actinin (ACTN2 and
      ACTN3) are major structural components of the Z-line involved in anchoring the
      actin-containing thin filaments. In humans, ACTN2 is expressed in all muscle
      fibres, while ACTN3 expression is restricted to a subset of type 2 fibres. We
      have recently demonstrated that alpha-actinin-3 is absent in approximately 18% of
      individuals in a range of human populations, and that homozygosity for a
      premature stop codon (577X) accounts for most cases of true alpha-actinin-3
      deficiency. Absence of alpha-actinin-3 is not associated with an obvious disease
      phenotype, raising the possibility that ACTN3 is functionally redundant in
      humans, and that alpha-actinin-2 is able to compensate for alpha-actinin-3
      deficiency. We now present data concerning the expression of ACTN3 in other
      species. Genotyping of non-human primates indicates that the 577X null mutation
      has likely arisen in humans. The mouse genome contains four orthologues which all
      map to evolutionarily conserved syntenic regions for the four human genes. Murine
      Actn2 and Actn3 are differentially expressed, spatially and temporally, during
      embryonic development and, in contrast to humans, alpha-actinin-2 expression does
      not completely overlap alpha-actinin-3 in postnatal skeletal muscle, suggesting
      independent function. Furthermore, sequence comparison of human, mouse and
      chicken alpha-actinin genes demonstrates that ACTN3 has been conserved over a
      long period of evolutionary time, implying a constraint on evolutionary rate
      imposed by continued function of the gene. These observations provide a real
      framework in which to test theoretical models of genetic redundancy as they apply
      to human populations. In addition we highlight the need for caution in making
      conclusions about gene function from the phenotypic consequences of loss-of
      function mutations in animal knockout models.

PMID- 11440987
TI  - Analysis of several endoglin mutants reveals no endogenous mature or secreted
      protein capable of interfering with normal endoglin function.
AB  - Hereditary hemorrhagic telangiectasia type 1 (HHT1) is associated with mutations
      in the ENDOGLIN gene which normally codes for a polypeptide of 653 amino acids
      expressed at the cell surface as a dimeric glycoprotein. To maximize the
      detection of potential mutant proteins, we analyzed by pulse-chase experiments
      the expression of large truncation mutants in endothelial cells from newborns
      with HHT1. A mutant truncated at residue 490 (Delta490) and the Delta517 mutant,
      previously suggested to act as dominant negative, were undetectable. Proteins
      Delta471 and Delta571 were barely detectable as transient monomers of 62 and 72
      kDa. A de novo 13 bp deletion in exon 11 encoded a monomeric protein of 70 kDa
      (Delta557), present at low levels in activated monocytes. Six novel missense
      mutants and DeltaS411 were expressed only as the 80 kDa intracellular precursor
      of surface endoglin, suggesting impaired processing. All nine novel mutations
      reported failed to be expressed other than intracellularly. Several constructs of
      endoglin were expressed in COS-1 cells; only the full-length protein was
      processed to the cell surface. Recombinant Delta586, corresponding to the
      complete extracellular domain, was secreted as monomeric and dimeric glycosylated
      species. Our studies show that all HHT1 mutants analyzed, although expressed to
      various degrees in COS-1 cells, are either undetectable, present at low levels as
      transient intracellular forms, or expressed as partially glycosylated precursors
      in endogenous cells. These mutants do not form heterodimers with normal endoglin
      and do not interfere with its normal trafficking to the cell surface, further
      supporting the haploinsufficiency model.

PMID- 11440988
TI  - OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for
      semi-dominant inheritance.
AB  - We and others have shown recently that mutations in the OPA1 gene encoding a
      dynamin-related mitochondrial protein cause autosomal dominant optic atrophy
      (ADOA) linked to chromosome 3q28-q29. Here we report screening of the OPA1 gene
      in a sample of 78 independent ADOA families. OPA1 mutations were identified in 25
      patients (detection rate 32.1%) including 16 novel mutations. We successfully
      amplified OPA1 cDNA prepared from leukocyte RNA of three patients, and found the
      amount of transcripts harboring the Arg366Stop mutation was significantly reduced
      compared with transcripts derived from the normal chromosome. Analysis of the
      distribution of OPA1 mutations in ADOA revealed that most missense mutations
      cluster within the putative GTPase domain, and that there is a preponderance of
      mutations, which result in premature translation termination. These observations
      support the notion that haploinsufficiency may represent a major pathomechanism
      for ADOA. In addition, we identified an ADOA patient who is a compound
      heterozygote for two OPA1 missense mutations. The fact that this patient is by
      far more severely affected than her simple heterozygotic parents and siblings
      implies that at least these OPA1 alleles behave semi-dominantly rather than
      purely dominantly. Clinical examination revealed considerable variability in
      disease expression among patients carrying OPA1 mutations and no strict
      correlation with either the position or the type of mutation.

PMID- 11440989
TI  - Spectrum, frequency and penetrance of OPA1 mutations in dominant optic atrophy.
AB  - Dominant optic atrophy (DOA) is the commonest form of inherited optic neuropathy.
      Although heterogeneous, a major locus has been mapped to chromosome 3q28 and the
      gene responsible, OPA1, was recently identified. We therefore screened a panel of
      35 DOA patients for mutations in OPA1. This revealed 14 novel mutations and a
      further three known mutations, which together accounted for 20 of the 35 families
      (57%) included in this study. This more than doubles the number of OPA1 mutations
      reported in the literature, bringing the total to 25. These are predominantly
      null mutations generating truncated proteins, strongly suggesting that the
      mechanism underlying DOA is haploinsufficiency. The mutations are largely family
      specific, although a common 4 bp deletion in exon 27 (eight different families)
      and missense mutations in exons 8 (two families) and 9 (two families) have been
      identified. Haplotype analysis of individuals with the exon 27 2708del(TTAG)
      mutation suggests that this is a mutation hotspot and not an ancient mutation,
      thus excluding a major founder effect at the OPA1 locus. The mutation screening
      in this study also identified a number of asymptomatic individuals with OPA1
      mutations. A re-calculation of the penetrance of this disorder within two of our
      families indicates figures as low as 43 and 62% associated with the 2708del(TTAG)
      mutation. If haploinsufficiency is the mechanism underlying DOA it is unlikely
      that this figure will be mutation-specific, indicating that the penetrance in DOA
      is much lower than the 98% reported previously. To investigate whether Leber's
      hereditary optic neuropathy (LHON) could be caused by mutations in OPA1 we also
      screened a panel of 28 LHON patients who tested negatively for the three major
      LHON mutations. No mutations were identified in any LHON patients, indicating
      that DOA and LHON are genetically distinct.

PMID- 11440990
TI  - Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33
      and Hashimoto's thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage
      analysis in Japanese.
AB  - Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's
      thyroiditis (HT), is caused by multiple genetic and environmental factors. The
      clinical and immunological features of GD and HT are distinct; however, there are
      multiplex families with both GD and HT, and cases in which GD evolves into HT.
      Thus, there may be specific susceptibility loci for GD or HT, and common loci
      controlling the susceptibility to both GD and HT may exist. A genome-wide
      analysis of data on 123 Japanese sib-pairs affected with AITD was made in which
      GD- or HT-affected sib-pairs (ASPs) were studied to detect GD- or HT-specific
      susceptibility loci, and all AITD-ASPs were used to detect AITD-common
      susceptibility loci. Our study revealed 19 regions on 14 chromosomes (1, 2, 3, 5,
      6, 8, 9, 10, 11, 12, 13, 15, 18 and 22) where the multipoint maximum LOD score
      (MLS) was >1. Especially, chromosome 5q31-q33 yielded suggestive evidence for
      linkage to AITD as a whole, with an MLS of 3.14 at D5S436, and chromosome 8q23
      q24 yielded suggestive evidence for linkage to HT, with an MLS of 3.77 at D8S272.
      These observations suggest the presence of an AITD susceptibility locus at 5q31
      q33 and a HT susceptibility locus at 8q23-q24.

PMID- 11440991
TI  - Recombination hotspot in NF1 microdeletion patients.
AB  - Neurofibromatosis type 1 (NF1) patients that are heterozygous for an NF1
      microdeletion are remarkable for an early age at onset and an excessive burden of
      dermal neurofibromas. Microdeletions are predominantly maternal in origin and
      arise by unequal crossover between misaligned NF1REP paralogous sequence blocks
      which flank the NF1 gene. We mapped and sequenced the breakpoints in several
      patients and designed primers within each paralog to specifically amplify a 3.4
      kb deletion junction fragment. This assay amplified a deletion junction fragment
      from 25 of the 54 unrelated NF1 microdeletion patients screened. Sequence
      analysis demonstrated that each of the 25 recombination events occurred in a
      discrete 2 kb recombination hotspot within each of the flanking NF1REPs. Two
      recombination events were accompanied by apparent gene conversion. A search for
      recombination-prone motifs revealed a chi-like sequence; however, it is unknown
      whether this element stimulates recombination to occur at the hotspot. The
      deletion-junction assay will facilitate the prospective identification of
      patients with NF1 microdeletion at this hotspot for genotype-phenotype
      correlation studies and diagnostic evaluation.

PMID- 11440992
TI  - Control of Xist expression for imprinted and random X chromosome inactivation in
      mice.
AB  - Applying RNA fluorescence in situ hybridization to parthenogenetic embryos with
      two maternally derived X (X(M)) chromosomes and embryos with X chromosome
      aneuploidy such as X(P)0 (X(P), paternally derived X chromosome), X(M)X(M)X(P)
      and X(M)X(M)Y, we studied the control of Xist/Tsix expression for silencing the
      entire X chromosome in mice. The data show that the paternally derived Xist
      allele is highly expressed in every cell of the embryo from the 4-cell stage
      onward, irrespective of the number of X chromosomes in a diploid cell. The high
      level of Xist transcription is maintained in non-epiblast cells culminating in
      X(P)-inactivation, whereas in X(P)0 embryos it is terminated by the blastocyst
      stage, probably as a result of counting the number of X chromosomes in a cell
      occurring at the morula/blastocyst stage. Xist is also down-regulated in epiblast
      cells of X(M)X(P) and X(M)X(M)X(P) embryos to make X-inactivation random. In
      epiblast cells, Xist seems to be up-regulated after counting and random choice of
      the future inactive X chromosome(s). Although the maternal Xist allele is never
      activated in fertilized embryos before implantation, some parthenogenetic embryos
      show Xist up-regulation in a proportion of cells. These and other data reported
      earlier suggest that imprinted X-inactivation in non-epiblast tissues of rodents
      had been derived from the random X-inactivation system.

PMID- 11440993
TI  - Tsix-mediated repression of Xist accumulation is not sufficient for normal random
      X inactivation.
AB  - During the X inactivation process, one X chromosome in each female embryonic cell
      is chosen at random to become coated by Xist RNA and silenced. Tsix, a transcript
      anti-sense to Xist, participates in the choice of the inactive X and in Xist
      regulation through as yet unknown mechanisms. Undifferentiated female ES cells,
      which have two active Xs, recapitulate random X inactivation when induced to
      differentiate. A 65 kb deletion targeted to one of the two Xs in a female ES cell
      line, and including both the end of the Xist gene and the site of initiation of
      Tsix, resulted in the exclusive inactivation of the deleted X in differentiated
      ES cells. We have re-examined the phenotype of the 65 kb deletion and targeted
      Tsix and the terminal exons of Xist back to the deleted locus using a cre/loxP
      site-specific re-insertion strategy. We show that prior to inactivation the
      deleted X is associated in undifferentiated ES cells with both increased Xist
      expression and diffusion of the Xist transcript away from its site of synthesis.
      Restoration of Tsix repressed the steady-state level of Xist expression and
      restricted Xist RNA to its transcription site. At the onset of inactivation in
      differentiated ES cells, restoration of Tsix failed to restore random X
      inactivation, even though the levels of Xist RNA accumulation in cis were
      markedly reduced. These results identify for the first time a dual function for
      Tsix as both a repressor of the steady-state level of Xist expression and as a
      regulator of the distribution of Xist RNA within the nucleus. They also establish
      that random inactivation requires mechanisms additional to the in cis repression
      of XIST:

PMID- 11440994
TI  - Excessive CpG island hypermethylation in cancer cell lines versus primary human
      malignancies.
AB  - Cancer cell lines are widely used in many types of cancer research, including
      studies aimed at understanding DNA hypermethylation of gene promoters in cancer.
      Hypermethylation of promoters is capable of repressing the expression of tumor
      suppressor genes and may play a role in the development and/or progression of
      cancer. Although both primary malignancies and cancer cell lines exhibit this
      epigenetic phenomenon, there has been no direct comparison between them. In order
      to address this question, we have utilized restriction landmark genomic scanning
      to measure the hypermethylation phenotypes of cancer cell lines and compared
      these data with the same analysis performed on primary malignancies. In all
      cases, cancer cell lines exhibit significantly higher levels of CpG island
      hypermethylation than the primary malignancies they represent. Colon cancer cell
      lines are most similar to their respective tumors, with only a 5-fold increase in
      hypermethylation, while head and neck squamous cell carcinoma cell lines show a
      93-fold increase in hypermethylation. Furthermore, >57% of the loci methylated in
      cell lines are never methylated in 114 primary malignancies studied. Seventy
      percent of loci hypermethylated in cell lines are hypermethylated in lines from
      more than one type of cancer. These data indicate that most CpG island
      hypermethylation observed in cancer cell lines is due to an intrinsic property of
      cell lines as opposed to the malignant tissue from which they originated.

PMID- 11440995
TI  - Localization of a novel susceptibility gene for familial ovarian cancer to
      chromosome 3p22-p25.
AB  - We performed genome-wide linkage analysis in 58 patients and nine unaffected
      members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of
      410 microsatellite markers. We initially screened the whole genome, including the
      X chromosome, by a non-parametric method using the GENEHUNTER program. As a
      result, chromosome 3p22-p25 showed a suggestive score for linkage [LOD = 3.49 and
      non-parametric LOD (NPL) = 2.77 at D3S3611] based on a multipoint analysis.
      Additionally, based on a two-point analysis using dense markers, this 3p22-p25
      region showed a P-value < 0.05 at 10 markers and there is suggestive evidence for
      linkage at two markers within approximately 19 cM (NPL = 2.60 and 2.49 at D3S1597
      and D3S3611, respectively). To explore whether the candidate gene in this 3p22
      p25 region contributed to carcinogenesis of familial ovarian cancer in a similar
      fashion to the tumor suppressor gene, we performed loss of heterozygosity (LOH)
      analysis. It was observed that the frequency of LOH at four markers in this
      region was >50% only in tumor tissues from patients with no mutation in BRCA1 or
      BRCA2, not in those with a BRCA1 mutation.

PMID- 11440996
TI  - Biochemical analysis of mutations in palmitoyl-protein thioesterase causing
      infantile and late-onset forms of neuronal ceroid lipofuscinosis.
AB  - Deficiency in a recently characterized lysosomal enzyme, palmitoyl-protein
      thioesterase (PPT), leads to a severe neurodegenerative disorder of children,
      infantile neuronal ceroid lipofuscinosis (NCL). Over 36 different mutations in
      the PPT gene have been described, and missense mutations have been interpreted in
      the light of the recently solved X-ray crystallographic structure of PPT. In the
      current study, we assessed the biochemical impact of mutations through the study
      of cells derived from patients and from the expression of recombinant PPT enzymes
      in COS and Sf9 cells. All missense mutations associated with infantile NCL showed
      no residual enzyme activity, whereas mutations associated with late-onset
      phenotypes showed up to 2.15% residual activity. Two mutations increased the K(m)
      of the enzyme for palmitoylated substrates and were located in positions that
      would distort the palmitate-binding pocket. An initiator methionine mutation (ATG
      ->ATA) in two late-onset patients was expressed at a significant level in COS
      cells, suggesting that the ATA codon may be utilized to a clinically important
      extent in vivo. The most common PPT nonsense mutation, R151X, was associated with
      an absence of PPT mRNA. Mannose 6-phosphate modification of wild-type and mutant
      PPT enzymes was grossly normal at the level of the phosphotransferase reaction.
      However, mutant PPT enzymes did not bind to mannose 6-phosphate receptors in a
      blotting assay. This observation was related to the failure of the mutant
      expressed enzymes to gain access to 'uncovering enzyme' (N-acetylglucosamine-1
      phosphodiester alpha-N-acetyl glucosaminidase), presumably due to a block in
      transit out of the endoplasmic reticulum, where mutant enzymes are degraded.

PMID- 11440997
TI  - DNA polymerase beta -mediated long patch base excision repair. Poly(ADP
      ribose)polymerase-1 stimulates strand displacement DNA synthesis.
AB  - Recently, photoaffinity labeling experiments with mouse cell extracts suggested
      that PARP-1 functions as a surveillance protein for a stalled BER intermediate.
      To further understand the role of PARP-1 in BER, we examined the DNA synthesis
      and flap excision steps in long patch BER using a reconstituted system containing
      a 34-base pair BER substrate and five purified human enzymes: uracil-DNA
      glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase beta, flap
      endonuclease-1 (FEN-1), and PARP-1. PARP-1 stimulates strand displacement DNA
      synthesis by DNA polymerase beta in this system; this stimulation is dependent on
      the presence of FEN-1. PARP-1 and FEN-1, therefore, cooperate to activate long
      patch BER. The results are discussed in the context of a model for BER sub
      pathway choice, illustrating a dual role for PARP-1 as a surveillance protein for
      a stalled BER intermediate and an activating factor for long patch BER DNA
      synthesis.

PMID- 11440998
TI  - Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial
      cells.
AB  - Protein networks asymetrically distributed to basolateral and apical epithelial
      membranes maintain cell polarity and homeostasis of epithelial tissues. Genetic
      studies in non-vertebrates assigned two families of basolateral proteins, MAGUK
      (membrane-associated and guanylate kinase) and LAP (leucine-rich repeats and PDZ)
      proteins, to a common pathway crucial for the epithelial architecture and acting
      as a gatekeeper to malignancy. In mammals, three LAP proteins have been
      described, Densin-180, Erbin, and hScribble. Here, we identify a protein called
      Lano (LAP and no PDZ) only present in vertebrates and presenting strong
      identities with LAP proteins. Despite the lack of PDZ domain, Lano is located at
      the basolateral side of epithelial cells in a similar manner to Erbin and
      hScribble. Using in vitro and in vivo experiments, we demonstrate that Lano
      directly interacts with the PDZ domains of MAGUK proteins, including hDLG (human
      disc large), in epithelial cells. A second pool of Lano is complexed to Erbin.
      These LAP-MAGUK protein complexes coexist at the basolateral side of epithelial
      cells. We provide evidence for a direct interaction between LAP and MAGUK
      proteins, and we propose that various LAP-MAGUK networks targeted to the
      basolateral side of epithelial cells participate to homeostasis of epithelial
      tissues and tumor growth.

PMID- 11440999
TI  - SopE and SopE2 from Salmonella typhimurium activate different sets of RhoGTPases
      of the host cell.
AB  - The bacterial enteropathogen Salmonella typhimurium employs a specialized type
      III secretion system to inject toxins into host cells, which trigger signaling
      cascades leading to cell death in macrophages, secretion of pro-inflammatory
      cytokines, or rearrangements of the host cell cytoskeleton and thus to bacterial
      invasion. Two of the injected toxins, SopE and the 69% identical protein SopE2,
      are highly efficient guanine nucleotide exchange factors for the RhoGTPase Cdc42
      of the host cell. However, it has been a puzzle why S. typhimurium might employ
      two toxins with redundant function. We hypothesized that SopE and SopE2 might
      have different specificities for certain host cellular RhoGTPases. In vitro
      guanine nucleotide exchange assays and surface plasmon resonance measurements
      revealed that SopE is an efficient guanine nucleotide exchange factor for Cdc42
      and Rac1, whereas SopE2 was interacting efficiently only with Cdc42, but not with
      Rac1. Affinity precipitation of Cdc42.GTP and Rac1.GTP from lysates and
      characteristic cytoskeletal rearrangements of infected tissue culture cells
      confirmed that SopE is highly efficient at activating Cdc42 and Rac1 in vivo,
      whereas SopE2 was efficiently activating Cdc42, but not Rac1. We conclude that
      the translocated effector proteins SopE and SopE2 allow S. typhimurium to
      specifically activate different sets of RhoGTPase signaling cascades.

PMID- 11441000
TI  - Biochemical and biophysical evidence for gamma 2 subunit association with
      neuronal voltage-activated Ca2+ channels.
AB  - A novel gene (Cacng2; gamma(2)) encoding a protein similar to the voltage
      activated Ca(2+) channel gamma(1) subunit was identified as the defective gene in
      the epileptic and ataxic mouse, stargazer. In this study, we analyzed the
      association of this novel neuronal gamma(2) subunit with Ca(2+) channels of
      rabbit brain, and the function of the gamma(2) subunit in recombinant neuronal
      Ca(2+) channels expressed in Xenopus oocytes. Our results showed that the
      gamma(2) subunit and a closely related protein (called gamma(3)) co-sedimented
      and co-immunoprecipitated with neuronal Ca(2+) channel subunits in vivo.
      Electrophysiological analyses showed that gamma(2) co-expression caused a
      significant decrease in the current amplitude of both alpha(1B)(alpha(1)2.2)
      class (36.8%) and alpha(1A)(alpha(1)2.1)-class (39.7%) Ca(2+) channels
      (alpha(1)beta(3)alpha(2)delta). Interestingly, the inhibitory effects of the
      gamma(2) subunit on current amplitude were dependent on the co-expression of the
      alpha(2)delta subunit. In addition, co-expression of gamma(2) or gamma(1) also
      significantly decelerates the activation kinetics of alpha(1B)-class Ca(2+)
      channels. Taken together, these results suggest that the gamma(2) subunit is an
      important constituent of the neuronal Ca(2+) channel complex and that it down
      regulates neuronal Ca(2+) channel activity. Furthermore, the gamma(2) subunit
      likely contributes to the fine-tuning of neuronal Ca(2+) channels by
      counterbalancing the effects of the alpha(2)delta subunit.

PMID- 11441001
TI  - Molecular mechanisms of ceramide-mediated telomerase inhibition in the A549 human
      lung adenocarcinoma cell line.
AB  - This study was aimed at identifying the molecular mechanisms by which ceramide
      inhibits telomerase activity in the A549 human lung adenocarcinoma cell line.
      C(6)-ceramide (20 microm) caused a significant reduction of telomerase activity
      at 24 h as detected using the telomeric repeat amplification protocol, and this
      inhibition correlated with decreased telomerase reverse transcriptase (hTERT)
      protein. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) and Northern blot analyses showed that C(6)-ceramide significantly decreased
      hTERT mRNA in a time-dependent manner. Electrophoretic mobility shift and
      supershift assays demonstrated that the binding activity of c-Myc transcription
      factor to the E-box sequence on the hTERT promoter was inhibited in response to
      C(6)-ceramide at 24 h. These results were also confirmed by transient
      transfections of A549 cells with pGL3-Basic plasmid constructs containing the
      functional hTERT promoter and its E-box deleted sequences cloned upstream of a
      luciferase reporter gene. Further analysis using RT-PCR and Western blotting
      showed that c-Myc protein but not its mRNA levels were decreased in response to
      C(6)-ceramide at 24 h. The effects of ceramide on the c-Myc protein were shown to
      be due to a reduction in half-life via increased ubiquitination. Similar results
      were obtained by increased endogenous ceramide levels in response to nontoxic
      concentrations of daunorubicin, resulting in the inhibition of telomerase and c
      Myc activities. Furthermore, the elevation of endogenous ceramide by
      overexpression of bacterial sphingomyelinase after transient transfections also
      induced the inhibition of telomerase activity with concomitant decreased hTERT
      and c-Myc protein levels. Taken together, these results show for the first time
      that both exogenous and endogenous ceramides mediate the modulation of telomerase
      activity via decreased hTERT promoter activity caused by rapid proteolysis of the
      ubiquitin-conjugated c-Myc transcription factor.

PMID- 11441002
TI  - Four subunit a isoforms of Caenorhabditis elegans vacuolar H+-ATPase. Cell
      specific expression during development.
AB  - We have identified four genes (vha-5, vha-6, vha-7, and unc-32) coding for
      vacuolar-type proton-translocating ATPase (V-ATPase) subunit a in Caenorhabditis
      elegans, the first example of four distinct isoforms in eukaryotes. Their
      products had nine putative transmembrane regions, exhibited 43-60% identity and
      62-84% similarity with the bovine subunit a1 isoform, and retained 11 amino acid
      residues essential for yeast V-ATPase activity (Leng, X. H., Manolson, M. F., and
      Forgac, M. (1998) J. Biol. Chem. 273, 6717-6723). The similarities, together with
      the results of immunoprecipitation, suggest that these isoforms are components of
      V-ATPase. Transgenic and immunofluorescence analyses revealed that these genes
      were strongly expressed in distinct cells; vha-5 was strongly expressed in an H
      shaped excretory cell, vha-6 was strongly expressed in intestine, vha-7 was
      strongly expressed in hypodermis, and unc-32 was strongly expressed in nerve
      cells. Furthermore, the vha-7 and unc-32 genes were also expressed in the uteri
      of hermaphrodites. RNA interference analysis showed that the double-stranded RNA
      for unc-32 caused embryonic lethality similar to that seen with other subunit
      genes (vha-1, vha-4, and vha-11) (Oka, T., and Futai, M. (2000) J. Biol. Chem.
      275, 29556-29561). The progenies of worms injected with the vha-5 or vha-6 double
      stranded RNA became died at a specific larval stage, whereas the vha-7 double
      stranded RNA showed no effect on development. These results suggest that V
      ATPases with these isoforms generate acidic compartments essential for worm
      development in a cell-specific manner.

PMID- 11441003
TI  - Amyloid beta-protein oligomerization: prenucleation interactions revealed by
      photo-induced cross-linking of unmodified proteins.
AB  - Assembly of the amyloid beta-protein (Abeta) into neurotoxic oligomers and
      fibrils is a seminal event in Alzheimer's disease. Understanding the earliest
      phases of Abeta assembly, including prenucleation and nucleation, is essential
      for the development of rational therapeutic strategies. We have applied a
      powerful new method, photoinduced cross-linking of unmodified proteins (PICUP),
      to the study of Abeta oligomerization. Significant advantages of this method
      include an extremely short reaction time, enabling the identification and
      quantification of short lived metastable assemblies, and the fact that no pre
      facto structural modification of the native peptide is required. Using PICUP, the
      distribution of Abeta oligomers existing prior to assembly was defined. A rapid
      equilibrium was observed involving monomer, dimer, trimer, and tetramer. A
      similar distribution was seen in studies of an unrelated amyloidogenic peptide,
      whereas nonamyloidogenic peptides yielded distributions indicative of a lack of
      monomer preassociation. These results suggest that simple nucleation-dependent
      polymerization models are insufficient to describe the dynamic equilibria
      associated with prenucleation phases of Abeta assembly.

PMID- 11441004
TI  - Vaccinia topoisomerase mutants illuminate conformational changes during closure
      of the protein clamp and assembly of a functional active site.
AB  - We present a mutational analysis of vaccinia topoisomerase that highlights the
      contributions of five residues in the catalytic domain (Phe-88 and Phe-101 in
      helix alpha1, Ser-204 in alpha5, and Lys-220 and Asn-228 in alpha6) to the DNA
      binding and transesterification steps. When augmented by structural information
      from exemplary type IB topoisomerases and tyrosine recombinases in different
      functional states, the results suggest how closure of the protein clamp around
      duplex DNA and assembly of a functional active site might be orchestrated by
      internal conformational changes in the catalytic domain. Lys-220 is a constituent
      of the active site, and a positive charge at this position is required for
      optimal DNA cleavage. Ser-204 and Asn-228 appear not to be directly involved in
      reaction chemistry at the scissile phosphodiester. We propose that (i) Asn-228
      recruits the Tyr-274 nucleophile to the active site by forming a hydrogen bond to
      the main chain of the tyrosine-containing alpha8 helix and that (ii) contacts
      between Ser-204 and the DNA backbone upstream of the cleavage site trigger a
      separate conformational change required for active site assembly. Mutations of
      Phe-88 and Phe-101 affect DNA binding, most likely at the clamp closure step,
      which we posit to entail a distortion of helix alpha1.

PMID- 11441005
TI  - Inhibition of protein phosphatase 2A overrides tau protein kinase I/glycogen
      synthase kinase 3 beta and cyclin-dependent kinase 5 inhibition and results in
      tau hyperphosphorylation in the hippocampus of starved mouse.
AB  - Hyperphosphorylated tau is the major component of paired helical filaments in
      neurofibrillary tangles found in Alzheimer's disease (AD) brain. Starvation of
      adult mice induces tau hyperphosphorylation at many paired helical filaments
      sites and with a similar regional selectivity as those in AD, suggesting that a
      common mechanism may be mobilized. Here we investigated the mechanism of
      starvation-induced tau hyperphosphorylation in terms of tau kinases and Ser/Thr
      protein phosphatases (PP), and the results were compared with those reported in
      AD brain. During starvation, tau hyperphosphorylation at specific epitopes was
      accompanied by decreases in tau protein kinase I/glycogen synthase kinase 3 beta
      (TPKI/GSK3 beta), cyclin-dependent kinase 5 (cdk5), and PP2A activities toward
      tau. These results demonstrate that the activation of TPKI/GSK3 beta and cdk5 is
      not necessary to obtain hyperphosphorylated tau in vivo, and indicate that
      inhibition of PP2A is likely the dominant factor in inducing tau
      hyperphosphorylation in the starved mouse, overriding the inhibition of key tau
      kinases such as TPKI/GSK3 beta and cdk5. Furthermore, these data give strong
      support to the hypothesis that PP2A is important for the regulation of tau
      phosphorylation in the adult brain, and provide in vivo evidence in support of a
      central role of PP2A in tau hyperphosphorylation in AD.

PMID- 11441006
TI  - Identification and properties of a novel intracellular (mitochondrial) ATP
      sensitive potassium channel in brain.
AB  - Protection of heart against ischemia-reperfusion injury by ischemic
      preconditioning and K(ATP) channel openers is known to involve the mitochondrial
      ATP-sensitive K(+) channel (mitoK(ATP)). Brain is also protected by ischemic
      preconditioning and K(ATP) channel openers, and it has been suggested that
      mitoK(ATP) may also play a key role in brain protection. However, it is not known
      whether mitoK(ATP) exists in brain mitochondria, and, if so, whether its
      properties are similar to or different from those of heart mitoK(ATP). We report
      partial purification and reconstitution of a new mitoK(ATP) from rat brain
      mitochondria. We measured K(+) flux in proteoliposomes and found that brain
      mitoK(ATP) is regulated by the same ligands as those that regulate mitoK(ATP)
      from heart and liver. We also examined the effects of opening and closing
      mitoK(ATP) on brain mitochondrial respiration, and we estimated the amount of
      mitoK(ATP) by means of green fluorescence probe BODIPY-FL-glyburide labeling of
      the sulfonylurea receptor of mitoK(ATP) from brain and liver. Three independent
      methods indicate that brain mitochondria contain six to seven times more
      mitoK(ATP) per milligram of mitochondrial protein than liver or heart.

PMID- 11441007
TI  - PDZ domain protein GIPC interacts with the cytoplasmic tail of melanosomal
      membrane protein gp75 (tyrosinase-related protein-1).
AB  - Tyrosinase and tyrosinase-related proteins (TRPs) are a family of melanosomal
      membrane proteins involved in mammalian pigmentation. Whereas the melanogenic
      functions of TRPs are localized in their amino-terminal domains that reside
      within the lumen of melanosomes, the sorting and targeting of these proteins to
      melanosomes is mediated by signals in their cytoplasmic domains. To identify
      proteins that interact with the cytoplasmic tail of gp75 (TRP-1), the most
      abundant melanosomal membrane protein, we performed yeast two-hybrid screening of
      a melanocyte cDNA library. Here, we show that the cytoplasmic domain of gp75
      interacts with a PDZ domain-containing protein. The gp75-interacting protein is
      identical to GIPC, an RGS (regulator of G protein signaling)/GAIP-interacting
      protein, and to SEMCAP-1, a transmembrane semaphorin-binding protein. Carboxyl
      terminal amino acid residues, Ser-Val-Val, of gp75 are necessary and sufficient
      for interaction of gp75 with the single PDZ domain in GIPC. Although endogenous
      and transfected GIPCs bind efficiently to transiently expressed gp75, only a
      small amount of GIPC is found associated with gp75 at steady state. Using a
      strategy to selectively synchronize the biosynthesis of endogenous gp75, we
      demonstrate that only newly synthesized gp75 associates with GIPC, primarily in
      the juxtanuclear Golgi region. Our data suggest that GIPC/SEMCAP-1 plays a role
      in biosynthetic sorting of proteins, specifically gp75, to melanosomes.

PMID- 11441008
TI  - Coordinated ATP hydrolysis by the Hsp90 dimer.
AB  - The Hsp90 dimer is a molecular chaperone with an unusual N-terminal ATP binding
      site. The structure of the ATP binding site makes it a member of a new class of
      ATP-hydrolyzing enzymes, known as the GHKL family. While for some of the family
      members structural data on conformational changes occurring after ATP binding are
      available, these are still lacking for Hsp90. Here we set out to investigate the
      correlation between dimerization and ATP hydrolysis by Hsp90. The dimerization
      constant of wild type (WT) Hsp90 was determined to be 60 nm. Heterodimers of WT
      Hsp90 with fragments lacking the ATP binding domain form readily and exhibit
      dimerization constants similar to full-length Hsp90. However, the ATPase activity
      of these heterodimers was significantly lower than that of the wild type protein,
      indicating cooperative interactions in the N-terminal part of the protein that
      lead to the activation of the ATPase activity. To further address the
      contribution of the N-terminal domains to the ATPase activity, we used an Hsp90
      point mutant that is unable to bind ATP. Since heterodimers between the WT
      protein and this mutant showed WT ATPase activity, this mutant, although unable
      to bind ATP, still has the ability to stimulate the activity in its WT partner
      domain. Thus, contact formation between the N-terminal domains might not depend
      on ATP bound to both domains. Together, these results suggest a mechanism for
      coupling the hydrolysis of ATP to the opening-closing movement of the Hsp90
      molecular chaperone.

PMID- 11441009
TI  - Acylation state of the phosphatidylinositol mannosides from Mycobacterium bovis
      bacillus Calmette Guerin and ability to induce granuloma and recruit natural
      killer T cells.
AB  - Previous studies have found that, when injected into mice, glycolipidic fractions
      of mycobacterial cell walls containing phosphatidylinositol mannosides (PIM)
      induced a granuloma and recruitment of Natural Killer T cells in the lesions. The
      dimannoside (PIM(2)) and the hexamannoside (PIM(6)) PIM were isolated from
      Mycobacterium bovis bacillus Calmette Guerin and shown to act alike, but the
      activity was found to be dependent on the presence of the lipidic part. The
      chemical structure of PIM was then re-evaluated, focusing on the characterization
      of their lipidic part, defining mono- to tetra-acylated PIM(2). The structure of
      these acyl forms was elucidated using a sophisticated combination of chemical
      degradations and analytical tools including electrospray ionization/mass
      spectrometry, electrospray ionization/mass spectrometry/mass spectrometry, and
      two-dimensional NMR. Finally, the acyl forms were purified by hydrophobic
      interaction chromatography and tested for their capacity to induce the granuloma
      and Natural Killer T cell recruitment. We found that there is an absolute
      requirement for the molecules to possess at least one fatty acyl chain, but the
      number, location, and size of the acyl chains was without effect. Moreover,
      increasing the complexity of the carbohydrate moiety did not lead to significant
      differences in the biological responses.

PMID- 11441010
TI  - Fusion of docked membranes requires the armadillo repeat protein Vac8p.
AB  - The discovery of molecules required for membrane fusion has revealed a remarkably
      conserved mechanism that centers upon the formation of a complex of SNARE
      proteins. However, whether the SNARE proteins or other components catalyze the
      final steps of membrane fusion in vivo remains unclear. Understanding this last
      step depends on the identification of molecules that act late in the fusion
      process. Here we demonstrate that in Saccharomyces cerevisiae, Vac8p, a
      myristoylated and palmitoylated armadillo repeat protein, is required for
      homotypic vacuole fusion. Vac8p is palmitoylated during the fusion reaction, and
      the ability of Vac8p to be palmitoylated appears to be necessary for its function
      in fusion. Both in vivo and in vitro analyses show that Vac8p functions after
      both Rab-dependent vacuole docking and the formation of trans-SNARE pairs. We
      propose that Vac8p may bind the fusion machinery through its armadillo repeats
      and that palmitoylation brings this machinery to a specialized lipid domain that
      facilitates bilayer mixing.

PMID- 11441011
TI  - Physical mapping of HIV reverse transcriptase to the 5' end of RNA primers.
AB  - Enzymatic analysis of RNA cleavage products has suggested that human
      immunodeficiency virus (HIV) reverse transcriptase (RT) binds to the 5' end of
      RNAs that are recessed on a longer DNA template (RNA primers) yet binds to the 3'
      end of DNA primers. One concern is that RT molecules bound at the 3' end of RNA
      would not be easily detected because RT may not catalyze substantial RNA
      extension or cleavage when bound to the 3' end. We used physical mapping to show
      that RT binds preferentially to the 5' end of RNA primers. An HIV-RT that lacked
      RNase H activity (HIV-RT(E478Q)) was incubated with the RNA-DNA hybrid followed
      by the addition of Escherichia coli RNase H. RT protected a approximately 23-base
      region at the 5' end of the RNA and 4 additional bases on the DNA strand. This
      footprint correlated well with the crystal structure of HIV-RT. No protection of
      the RNA 3' end was observed, although when dNTPs were included, low levels of
      extension occurred, indicating that RT can bind this end. Wild-type HIV-RT
      cleaved the RNA and then extended a small portion of the cleaved fragments,
      suggesting that very small RNAs may be bound similar to DNA primers.

PMID- 11441012
TI  - Ultraviolet B-induced phosphorylation of histone H3 at serine 28 is mediated by
      MSK1.
AB  - N-terminal tail phosphorylation of histone H3 plays an important role in gene
      expression, chromatin remodeling, and chromosome condensation. Phosphorylation of
      histone H3 at serine 10 was shown to be mediated by RSK2, mitogen- and stress
      activated protein kinase-1 (MSK1), and mitogen-activated protein kinases
      depending on the specific stimulation or stress. Our previous study showed that
      mitogen-activated protein kinases MAP kinases are involved in ultraviolet B
      induced phosphorylation of histone H3 at serine 28 (Zhong, S., Zhong, Z., Jansen,
      J., Goto, H., Inagaki, M., and Dong, Z., J. Biol. Chem. 276, 12932-12937).
      However, downstream effectors of MAP kinases remain to be identified. Here, we
      report that H89, a selective inhibitor of the nucleosomal response, totally
      inhibits ultraviolet B-induced phosphorylation of histone H3 at serine 28. H89
      blocks MSK1 activity but does not inhibit ultraviolet B-induced activation of MAP
      kinases p70/85(S6K), p90(RSK), Akt, and protein kinase A. Furthermore, MSK1
      markedly phosphorylated serine 28 of histone H3 and chromatin in vitro.
      Transfection experiments showed that an N-terminal mutant MSK1 or a C-terminal
      mutant MSK1 markedly blocked MSK1 activity. Compared with wild-type MSK1, cells
      transfected with N-terminal or C-terminal mutant MSK1 strongly blocked
      ultraviolet B-induced phosphorylation of histone H3 at serine 28 in vivo. These
      data illustrate that MSK1 mediates ultraviolet B-induced phosphorylation of
      histone H3 at serine 28.

PMID- 11441013
TI  - Pathogenic effects of D23N Iowa mutant amyloid beta -protein.
AB  - Cerebral amyloid beta-protein angiopathy (CAA) is a key pathological feature of
      patients with Alzheimer's disease and certain related disorders. In these
      conditions the CAA is characterized by the deposition of Abeta within the
      cerebral vessel wall and, in severe cases, hemorrhagic stroke. Several mutations
      have been identified within the Abeta region of the Abeta protein precursor
      (AbetaPP) gene that appear to enhance the severity of CAA. We recently described
      a new mutation within the Abeta region (D23N) of AbetaPP that is associated with
      severe CAA in an Iowa kindred (Grabowski, T. J., Cho, H. S., Vonsattel, J. P. G.,
      Rebeck, G. W., and Greenberg, S. M. (2001) Ann. Neurol. 49, 697-705). In the
      present study, we investigated the effect of this new D23N mutation on the
      processing of AbetaPP and the pathogenic properties of Abeta. Neither the D23N
      Iowa mutation nor the E22Q Dutch mutation affected the amyloidogenic processing
      of AbetaPP expressed in H4 cells. The A21G Flemish mutation, in contrast,
      resulted in a 2.3-fold increase in secreted Abeta peptide. We also tested
      synthetic wild-type and mutant Abeta40 peptides for fibrillogenesis and toxicity
      toward cultured human cerebrovascular smooth muscle (HCSM) cells. The E22Q Dutch,
      D23N Iowa, and E22Q,D23N Dutch/Iowa double mutant Abeta40 peptides rapidly
      assembled in solution to form fibrils, whereas wild-type and A21G Flemish Abeta40
      peptides exhibited little fibril formation. Similarly, the E22Q Dutch and D23N
      Iowa Abeta40 peptides were found to induce robust pathologic responses in
      cultured HCSM cells, including elevated levels of cell-associated AbetaPP,
      proteolytic breakdown of smooth muscle cell alpha-actin, and cell death. Double
      mutant E22Q,D23N Dutch/Iowa Abeta40 was more potent than either single mutant
      form of Abeta in causing pathologic responses in HCSM cells. These data suggest
      that the different CAA mutations in AbetaPP may exert their pathogenic effects
      through different mechanisms. Whereas the A21G Flemish mutation appears to
      enhance Abeta production, the E22Q Dutch and D23N Iowa mutations enhance
      fibrillogenesis and the pathogenicity of Abeta toward HCSM cells.

PMID- 11441014
TI  - Transmembrane domains 4 and 7 of the M(1) muscarinic acetylcholine receptor are
      critical for ligand binding and the receptor activation switch.
AB  - Activation of the muscarinic acetylcholine receptors requires agonist binding
      followed by a conformational change, but the ligand binding and conformation
      switching residues have not been completely identified. Systematic alanine
      scanning mutagenesis has been used to assess residues 142-164 in transmembrane
      helix 4 and 402-421 in transmembrane helix 7 of the M(1) muscarinic acetylcholine
      receptor. Several inward-facing amino acid side chains in the exofacial parts of
      transmembrane helices 4 and 7 contribute to acetylcholine binding. Alanine
      substitution of the aromatic residues in this group reduced signaling efficacy,
      suggesting that they may form part of a charge-stabilized aromatic cage, which
      triggers rotation and movement of the transmembrane helices. The mutation of
      adjacent residues modulated receptor activation, either reducing signaling or
      causing constitutive activation. In the buried endofacial section of
      transmembrane helix 7, alanine substitution mutants of the conserved NSXXNPXXY
      motif displayed strongly reduced signaling efficacy, despite having increased or
      unchanged acetylcholine affinity. These residues may have dual functions, forming
      intramolecular contacts that stabilize the receptor in the inactive ground state,
      but that are broken, allowing them to form new intramolecular bonds in the
      activated state. This conformational rearrangement is critical to produce a G
      protein binding site and may represent a key mechanism of receptor activation.

PMID- 11441015
TI  - Dissection of the regional roles of the archaeal Holliday junction resolvase Hjc
      by structural and mutational analyses.
AB  - Hjc is an archaeal DNA endonuclease, which resolves the Holliday junction in the
      presence of divalent metals. Combined with mutational analyses, the x-ray
      structure of the Pyrococcus furiosus Hjc crystal grown in the presence of
      ammonium sulfate revealed a positively charged interface, rich in conserved basic
      residues, and the catalytic center (Nishino, T., Komori, K., Tsuchiya, D.,
      Ishino, Y., and Morikawa, K. (2001) Structure 9, 197-T204). This structural study
      also suggested that the N-terminal segment and some loops of Hjc play crucial
      roles in the cleavage of DNA. However, a structural view of the interaction
      between these regions and DNA remains elusive. To clarify the regional roles of
      Hjc in the recognition of the Holliday junction, further structural and
      biochemical analyses were carried out. A new crystal form of Hjc was obtained
      from a polyethylene glycol solution in the absence of ammonium sulfate, and its
      structure has been determined at 2.16-A resolution. A comparison of the two
      crystal structures has revealed that the N-terminal segment undergoes a serious
      conformational change. The site-directed mutagenesis of the sulfate-binding site
      within the segment caused a dramatic decrease in the junction binding, but the
      mutant was still capable of cleaving DNA with a 20-fold lower efficiency. The
      kinetic analysis of Hjc-Holliday junction interaction indicated that mutations in
      the N-terminal segment greatly increased the dissociation rate constants of the
      Hjc-Holliday junction complex, explaining the decreased stability of the complex.
      This segment is also responsible for the disruption of base pairs near the
      junction center, through specific interactions with them. Taken together, these
      results imply that, in addition to the secondary effects of two basic loops, the
      flexible N-terminal segment plays predominant roles in the recognition of DNA
      conformation near the crossover and in correct positioning of the cleavage site
      to the catalytic center of the Hjc resolvase.

PMID- 11441016
TI  - Role of DNA end distortion in catalysis by avian sarcoma virus integrase.
AB  - Retroviral integrase (IN) recognizes linear viral DNA ends and introduces nicks
      adjacent to a highly conserved CA dinucleotide usually located two base pairs
      from the 3'-ends of viral DNA (the "processing" reaction). In a second step, the
      same IN active site catalyzes the insertion of these ends into host DNA (the
      "joining" reaction). Both DNA sequence and DNA structure contribute to specific
      recognition of viral DNA ends by IN. Here we used potassium permanganate
      modification to show that the avian sarcoma virus IN catalytic domain is able to
      distort viral DNA ends in vitro. This distortion activity is consistent with both
      unpairing and unstacking of the three terminal base pairs, including the
      processing site adjacent to the conserved CA. Furthermore, the introduction of
      mismatch mutations that destabilize the viral DNA ends were found to stimulate
      the IN processing reaction as well as IN-mediated distortion. End-distortion
      activity was also observed with mutant or heterologous DNA substrates. However,
      further analyses showed that using Mn(2+) as a cofactor, processing site
      specificity of these substrates was also maintained. Our results support a model
      whereby unpairing and unstacking of the terminal base pairs is a required step in
      the processing reaction. Furthermore, these results are consistent with our
      previous observations indicating that unpairing of target DNA promotes the
      joining reaction.

PMID- 11441017
TI  - Expression and localization of the mouse homologue of the yeast V-ATPase 21-kDa
      Subunit c" (Vma16p).
AB  - We have identified a cDNA encoding the mouse homologue of the yeast V-ATPase 21
      kDa subunit c" (Vma16p). The encoded protein contains 205 amino acid residues
      with five putative membrane spanning segments and shows 48% identity and 64%
      similarity to the yeast protein. Despite this homology, however, the mouse cDNA
      does not complement the phenotype of a yeast strain in which the VMA16 gene has
      been disrupted. Northern blot analysis demonstrated that the 21-kDa subunit is
      expressed in most tissues examined and showed an expression pattern almost
      identical to that of the 16-kDa proteolipid subunit (subunit c). The presence of
      multiple mRNA species suggests the existence of alternatively spliced forms of
      the 21-kDa subunit which, from Southern blot analysis, are derived from a single
      gene. Promoter analysis using the luciferase reporter gene revealed that a region
      186 bases upstream of the initiation site is sufficient to show a low level of
      transcriptional activity but that transcription is significantly enhanced by
      inclusion of the region -186 to -706. The 21-kDa protein was Myc-tagged and the
      16-kDa protein was HA-tagged and the tagged proteins were co-expressed in COS-1
      cells in order to study their intracellular localization by immunofluorescence
      microscopy. Both proteins showed significant punctate and perinuclear staining
      and were predominantly co-localized throughout the cell, consistent with their
      presence in the same V(0) complexes. Selective permeabilization of cells with
      digitonin (to permeabilize the plasma membrane) or Triton X-100 (to permeabilize
      both intracellular and plasma membranes) followed by immunofluorescence
      microscopy revealed that the carboxyl terminus of the 21-kDa subunit is exposed
      on the cytoplasmic side of the membrane whereas the carboxyl terminus of the 16
      kDa subunit is located on the lumenal side of the membrane.

PMID- 11441018
TI  - Regulation of an IMP dehydrogenase gene and its overexpression in drug-sensitive
      transcription elongation mutants of yeast.
AB  - IMP dehydrogenase is a rate-limiting enzyme involved in the synthesis of GTP. In
      mammalian cells it is regulated with respect to growth rate and is the target of
      numerous therapeutic agents. Mutations in the RNA polymerase II elongation
      machinery render yeast sensitive to inhibitors of IMP dehydrogenase and defective
      in inducing transcription of one of the IMP dehydrogenase-encoding genes, IMD2.
      Here we show that loss of IMD2, but not IMD1, IMD3, or IMD4, conferred upon yeast
      the same drug sensitivity found in elongation mutants. We tested whether the drug
      sensitivity of elongation mutants is due to their inability to induce IMD2 by
      providing them with exogenous copies of the gene. In some elongation mutants,
      overexpression reversed drug sensitivity and a transcriptional defect.
      Overexpression in mutants with a more severe phenotype partially suppressed drug
      sensitivity but was inconsequential in reversing a defect in transcription. These
      findings suggest that the drug sensitivity of elongation mutants is largely but
      not solely attributable to defects in the ability to induce IMD2, because
      transcription is compromised even when IMD2 mRNA levels are adequate. We describe
      two DNA sequence elements in the promoter of the gene that regulate it. We also
      found that IMD2 mRNA abundance is coupled to cell growth rate. These findings
      show that yeast possess a conserved system that gauges nucleotide pools and cell
      growth rate and responds through a uniquely regulated member of the IMD gene
      family.

PMID- 11441019
TI  - DNA chain length dependence of formation and dynamics of
      hMutSalpha.hMutLalpha.heteroduplex complexes.
AB  - Formation of a ternary complex between human MutSalpha, MutLalpha, and
      heteroduplex DNA has been demonstrated by surface plasmon resonance spectroscopy
      and electrophoretic gel shift methods. Formation of the
      hMutLalpha.hMutSalpha.heteroduplex complex requires a mismatch and ATP
      hydrolysis, and depends on DNA chain length. Ternary complex formation was
      supported by a 200-base pair G-T heteroduplex, a 100-base pair substrate was
      somewhat less effective, and a 41-base pair heteroduplex was inactive. As judged
      by surface plasmon resonance spectroscopy, ternary complexes produced with the
      200-base pair G-T DNA contained approximately 0.8 mol of hMutLalpha/mol of
      heteroduplex-bound hMutSalpha. Although the steady-state levels of the
      hMutLalpha.hMutSalpha. heteroduplex were substantial, this complex was found to
      turn over, as judged by surface plasmon resonance spectroscopy and
      electrophoretic gel shift analysis. With the former method, the majority of the
      complexes dissociated rapidly upon termination of protein flow, and dissociation
      occurred in the latter case upon challenge with competitor DNA. However, ternary
      complex dissociation as monitored by gel shift assay was prevented if both ends
      of the heteroduplex were physically blocked with streptavidin.biotin complexes.
      This observation suggests that, like hMutSalpha, the hMutLalpha.hMutSalpha
      complex can migrate along the helix contour to dissociate at DNA ends.

PMID- 11441020
TI  - Structural basis for the thioredoxin-like activity profile of the glutaredoxin
      like NrdH-redoxin from Escherichia coli.
AB  - NrdH-redoxin is a representative of a class of small redox proteins that contain
      a conserved CXXC motif and are characterized by a glutaredoxin-like amino acid
      sequence and thioredoxin-like activity profile. The crystal structure of
      recombinant Escherichia coli NrdH-redoxin in the oxidized state has been
      determined at 1.7 A resolution by multiwavelength anomalous diffraction. NrdH
      redoxin belongs to the thioredoxin superfamily and is structurally most similar
      to E. coli glutaredoxin 3 and phage T4 glutaredoxin. The angle between the C
      terminal helix alpha3 and strand beta4, which differs between thioredoxin and
      glutaredoxin, has an intermediate value in NrdH-redoxin. The orientation of this
      helix is to a large extent determined by an extended hydrogen-bond network
      involving the highly conserved sequence motif (61)WSGFRP(D/E)(67), which is
      unique to this subclass of the thioredoxin superfamily. Residues that bind
      glutathione in glutaredoxins are in general not conserved in NrdH-redoxin, and no
      glutathione-binding cleft is present. Instead, NrdH-redoxin contains a wide
      hydrophobic pocket at the surface, similar to thioredoxin. Modeling studies
      suggest that NrdH-redoxin can interact with E. coli thioredoxin reductase at this
      pocket and also via a loop that is complementary to a crevice in the reductase in
      a similar manner as observed in the E. coli thioredoxin-thioredoxin reductase
      complex.

PMID- 11441021
TI  - Bag-1M accelerates nucleotide release for human Hsc70 and Hsp70 and can act
      concentration-dependent as positive and negative cofactor.
AB  - The cytosol of mammalian cells contains several Hsp70 chaperones and an arsenal
      of cochaperones, including the anti-apoptotic Bag-1M protein, which regulate the
      activities of Hsp70s by controlling their ATPase cycles. To elucidate the
      regulatory function of Bag-1M, we determined its influence on nucleotide
      exchange, substrate release, ATPase rate, and chaperone activity of the
      housekeeping Hsc70 and stress-inducible Hsp70 homologs of humans. Bag-1M and a C
      terminal fragment of it are potent nucleotide exchange factors as they stimulated
      the ADP dissociation rate of Hsc70 and Hsp70 up to 900-fold. The N-terminal
      domain of Bag-1M decreased the affinity of Bag-1M for Hsc70/Hsp70 by 4-fold,
      indicating a modulating role of the N terminus in Bag-1M action as nucleotide
      exchange factor. Bag-1M inhibited Hsc70/Hsp70-dependent refolding of luciferase
      in the absence of P(i). Surprisingly, under physiological conditions, i.e. low
      Bag-1M concentrations and presence of P(i), Bag-1M activates the chaperone action
      of Hsc70/Hsp70 in luciferase refolding. Bag-1M accelerated ATP-triggered
      substrate release by Hsc70/Hsp70. We propose that Bag-1M acts as substrate
      discharging factor for Hsc70 and Hsp70.

PMID- 11441022
TI  - Structural investigation of the biosynthesis of alternative lower ligands for
      cobamides by nicotinate mononucleotide: 5,6-dimethylbenzimidazole
      phosphoribosyltransferase from Salmonella enterica.
AB  - Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole
      phosphoribosyltransferase (CobT) from Salmonella enterica plays a central role in
      the synthesis of alpha-ribazole, a key component of the lower ligand of
      cobalamin. Surprisingly, CobT can phosphoribosylate a wide range of aromatic
      substrates, giving rise to a wide variety of lower ligands in cobamides. To
      understand the molecular basis for this lack of substrate specificity, the x-ray
      structures of CobT complexed with adenine, 5-methylbenzimidazole, 5
      methoxybenzimidazole, p-cresol, and phenol were determined. Furthermore, adenine,
      5-methylbenzimidazole, 5-methoxybenzimidazole, and 2-hydroxypurine were observed
      to react with NaMN within the crystal lattice and undergo the phosphoribosyl
      transfer reaction to form product. Significantly, the stereochemistries of all
      products are identical to those found in vivo. Interestingly, p-cresol and
      phenol, which are the lower ligand in Sporomusa ovata, bound to CobT but did not
      react with NaMN. This study provides a structural explanation for how CobT can
      phosphoribosylate most of the commonly observed lower ligands found in cobamides
      with the exception of the phenolic lower ligands observed in S. ovata. This is
      accomplished with minor conformational changes in the side chains that constitute
      the 5,6-dimethylbenzimidazole binding site. These investigations are consistent
      with the implication that the nature of the lower ligand is controlled by
      metabolic factors rather by the specificity of the phosphoribosyltransferase.

PMID- 11441023
TI  - The Ski protein family is required for MeCP2-mediated transcriptional repression.
AB  - DNA methylation is essential for development in the mouse and plays an important
      role in inactivation of the X chromosome and genomic imprinting. MeCP2 is the
      founder member of a family of methyl-CpG-binding proteins. MeCP2 directly binds
      to the co-repressor mSin3, which interacts with class I histone deacetylase,
      recruiting them to methyl-CpG regions to suppress transcription. Here, we report
      that MeCP2 directly binds to two co-repressors, c-Ski and N-CoR, in addition to
      mSin3A, and that the c-Ski, which is encoded by the c-ski proto-onocogene, is
      required for MeCP2-mediated transcriptional repression. The two regions of c-Ski,
      including the C-terminal coiled-coil region, interact with the transcriptional
      repression domain in the center of the MeCP2 molecule. The immunostaining signals
      for c-Ski and MeCP2 overlap in the nuclear heterochromatin region, suggesting the
      co-localization of the two proteins. The degree of transcriptional repression
      mediated by a Gal4-MeCP2 fusion protein was abrogated by overexpression of the
      putative dominant negative form of c-Ski. Furthermore, injection of antibodies
      against c-Ski and Sno almost completely abolished the transcriptional repression
      mediated by the Gal4-MeCP2 fusion protein. These results suggest that the ski
      gene family is involved in methyl CpG-mediated transcriptional repression.

PMID- 11441024
TI  - Conformational diversity versus nucleic acid triplex stability, a combinatorial
      study.
AB  - The stability of a triple helix formed between a DNA duplex and an incoming
      oligonucleotide strand strongly depends on the solvent conditions and on
      intrinsic chemical and conformational factors. Attempts to increase triple helix
      stability in the past included chemical modification of the backbone, sugar ring,
      and bases in the third strand. However, the predictive power of such
      modifications is still rather poor. We therefore developed a method that allows
      for rapid screening of conformationally diverse third strand oligonucleotides for
      triplex stability in the parallel pairing motif to a given DNA double helix
      sequence. Combinatorial libraries of oligonucleotides of the requisite (fixed)
      base composition and length that vary in their sugar unit (ribose or deoxyribose)
      at each position were generated. After affinity chromatography against their
      corresponding immobilized DNA target duplex, utilizing a temperature gradient as
      the selection criterion, the oligonucleotides forming the most stable triple
      helices were selected and characterized by physicochemical methods. Thus, a
      series of oligonucleotides were identified that allowed us to define basic rules
      for triple helix stability in this conformationally diverse system. It was found
      that ribocytidines in the third strand increase triplex stability relative to
      deoxyribocytidines independently of the neighboring bases and position along the
      strand. However, remarkable sequence-dependent differences in stability were
      found for (deoxy)thymidines and uridines.

PMID- 11441025
TI  - Plasminogen activator inhibitor-1 regulates tumor growth and angiogenesis.
AB  - Elevated expression of plasminogen activator inhibitor-1 (PAI-1) in tumors is
      associated with a poor prognosis in many cancers. Reduced tumor growth and
      angiogenesis have also been reported in mice deficient in PAI-1. These results
      suggest that PAI-1 may be required for efficient angiogenesis and tumor growth.
      In the present study, we demonstrate that PAI-1 can both enhance and inhibit the
      growth of M21 human melanoma tumors in nude mice and that this appears to be due
      to PAI-1 regulation of angiogenesis. Quantitative analysis of angiogenesis in a
      Matrigel implant assay indicated that in PAI-1 null mice angiogenesis was reduced
      approximately 60% compared with wild-type mice, while in mice overexpressing PAI
      1, angiogenesis was increased nearly 3-fold. Furthermore, addition of PAI-1 to
      implants in wild-type mice enhanced angiogenesis up to 3-fold at low
      concentrations but inhibited angiogenesis nearly completely at high
      concentrations. Together, these data demonstrate that PAI-1 is a potent regulator
      of angiogenesis and hence of tumor growth and suggest that understanding the
      mechanism of this activity may lead to the development of important new
      therapeutic agents for controlling pathologic angiogenesis.

PMID- 11441026
TI  - Osmoregulation in marine mammals.
AB  - Osmoregulation in marine mammals has been investigated for over a century;
      however, a review of recent advances in our understanding of water and
      electrolyte balance and of renal function in marine mammals is warranted. The
      following topics are discussed: (i) kidney structure and urine concentrating
      ability, (ii) sources of water, (iii) the effects of feeding, fasting and diving,
      (iv) the renal responses to infusions of varying salinity and (v) hormonal
      regulation. The kidneys of pinnipeds and cetaceans are reniculate in structure,
      unlike those of terrestrial mammals (except bears), but this difference does not
      confer any greater concentrating ability. Pinnipeds, cetaceans, manatees and sea
      otters can concentrate their urine above the concentration of sea water, but only
      pinnipeds and otters have been shown to produce urine concentrations of Na+ and
      Cl- that are similar to those in sea water. This could afford them the capacity
      to drink sea water and not lose fresh water. However, with few exceptions,
      drinking is not a common behavior in pinnipeds and cetaceans. Water balance is
      maintained in these animals via metabolic and dietary water, while incidental
      ingestion and dietary salt may help maintain electrolyte homeostasis. Unlike most
      other aquatic mammals, sea otters commonly drink sea water and manatees
      frequently drink fresh water. Among the various taxonomic groups of marine
      mammals, the sensitivity of the renin-angiotensin-aldosterone system appears to
      be influenced by the availability of Na+. The antidiuretic role of vasopressin
      remains inconclusive in marine mammals, while the natriuretic function of atrial
      natriuretic peptide has yet to be examined. Ideas on the direction of future
      studies are presented.

PMID- 11441027
TI  - Redox state, reactive oxygen species and adaptive growth in colonial hydroids.
AB  - Colonial metazoans often encrust surfaces over which the food supply varies in
      time or space. In such an environment, adaptive colony development entails
      adjusting the timing and spacing of feeding structures and gastrovascular
      connections to correspond to this variable food supply. To investigate the
      possibility of such adaptive growth, within-colony differential feeding
      experiments were carried out using the hydroid Podocoryna carnea. Indeed, such
      colonies strongly exhibited adaptive growth, developing dense arrays of polyps
      (feeding structures) and gastrovascular connections in areas that were fed
      relative to areas that were starved, and this effect became more consistent over
      time. To investigate mechanisms of signaling between the food supply and colony
      development, measurements were taken of metabolic parameters that have been
      implicated in signal transduction in other systems, particularly redox state and
      levels of reactive oxygen species. Utilizing fluorescence microscopy of P. carnea
      cells in vivo, simultaneous measurements of redox state [using NAD(P)H] and
      hydrogen peroxide (using 2',7'-dichlorofluorescin diacetate) were taken. Both
      measures focused on polyp epitheliomuscular cells, since these exhibit the
      greatest metabolic activity. Colonies 3-5h after feeding were relatively
      oxidized, with low levels of peroxide, while colonies 24h after feeding were
      relatively reduced, with high levels of peroxide. The functional role of polyps
      in feeding and generating gastrovascular flow probably produced this dichotomy.
      Polyps 3-5h after feeding contract maximally, and this metabolic demand probably
      shifts the redox state in the direction of oxidation and diminishes levels of
      reactive oxygen species. In contrast, 24h after feeding, polyps are quiescent,
      and this lack of metabolic demand probably shifts the redox state in the
      direction of reduction and increases levels of reactive oxygen species. Within
      colony differential feeding experiments were carried out on colonies 24h after
      the usual, colony-wide feeding. At this time, a single polyp was fed, and this
      polyp was compared with an otherwise similar polyp from the same colony. A
      pattern similar to the whole-colony experiments was obtained: the just-fed polyp,
      as it begins contracting shortly after feeding, appears to be relatively
      oxidized, with low levels of peroxide compared with the polyp that was not fed.
      These data are consistent with the hypothesis that adaptive colony development in
      response to a variable food supply is mediated by redox state or reactive oxygen
      species or both, although alternative hypotheses are also discussed.

PMID- 11441028
TI  - The vortex wake of the free-swimming larva and pupa of Culex pipiens (Diptera).
AB  - The kinematics and hydrodynamics of free-swimming pupal and larval (final-instar)
      culicids were investigated using videography and a simple wake-visualisation
      technique (dyes). In both cases, swimming is based on a technique of high
      amplitude, side-to-side (larva) or up-and-down (pupa) bending of the body. The
      pupa possesses a pair of plate-like abdominal paddles; the larval abdominal
      paddle consists of a fan of closely spaced bristles which, at the Reynolds
      numbers involved, behaves like a continuous surface. Wake visualisation showed
      that each half-stroke of the swimming cycle produces a discrete ring vortex that
      is convected away from the body. Consecutive vortices are produced first to one
      side then to the other of the mean swimming path, the convection axis being
      inclined at approximately 25 degrees away from dead aft. Pupal and larval
      culicids therefore resemble fish in using the momentum injected into the water to
      generate thrust. Preliminary calculations for the pupa suggest that each vortex
      contains sufficient momentum to account for that added to the body with each half
      stroke. The possibility is discussed that the side-to-side flexural technique may
      allow an interaction between body and tail flows in the production of vorticity.

PMID- 11441029
TI  - A Drosophila melanogaster strain from sub-equatorial Africa has exceptional
      thermotolerance but decreased Hsp70 expression.
AB  - Drosophila melanogaster collected in sub-equatorial Africa in the 1970s are
      remarkably tolerant of sustained laboratory culture above 30 degrees C and of
      acute exposure to much warmer temperatures. Inducible thermotolerance of high
      temperatures, which in Drosophila melanogaster is due in part to the inducible
      molecular chaperone Hsp70, is only modest in this strain. Expression of Hsp70
      protein and hsp70 mRNA is likewise reduced and has slower kinetics in this strain
      (T) than in a standard wild-type strain (Oregon R). These strains also differed
      in constitutive and heat-inducible levels of other molecular chaperones. The
      lower Hsp70 expression in the T strain apparently has no basis in the activation
      of the heat-shock transcription factor HSF, which is similar in T and Oregon R
      flies. Rather, the reduced expression may stem from insertion of two transposable
      elements, H.M.S. Beagle in the intergenic region of the 87A7 hsp70 gene cluster
      and Jockey in the hsp70Ba gene promoter. We hypothesize that the reduced Hsp70
      expression in a Drosophila melanogaster strain living chronically at intermediate
      temperatures may represent an evolved suppression of the deleterious phenotypes
      of Hsp70.

PMID- 11441030
TI  - In vitro effects of environmental salinity and cortisol on chloride cell
      differentiation in embryos of Mozambique tilapia, Oreochromis mossambicus,
      measured using a newly developed 'yolk-ball' incubation system.
AB  - To examine the functional differentiation of chloride cells in the yolk-sac
      membrane of tilapia (Oreochromis mossambicus) embryos, we developed a 'yolk-ball'
      incubation system in which the yolk sac was separated from the embryonic body and
      subjected to incubation in vitro. The yolk-ball preparation consists of the yolk
      and the covering yolk-sac membrane, which contains a rich population of chloride
      cells. After appropriate cutting, the incision on the yolk ball healed during
      incubation in balanced salt solution for 3h, so that the yolk-sac membrane
      completely enclosed the yolk. Yolk balls prepared from freshwater-acclimated
      embryos were transferred either to fresh water or to sea water and incubated for
      48 and 96 h to elucidate the morphological changes in the chloride cells in
      response to environmental salinity. The chloride cells in the yolk-sac membrane
      were larger in sea water than in fresh water. In yolk balls transferred to sea
      water, chloride cells often formed multicellular complexes characteristic of
      seawater-type chloride cells. In those transferred to fresh water, however, the
      cells were small and rarely formed such complexes. These responses of chloride
      cells were identical to those observed in intact embryos. Thus, chloride cells in
      the yolk-sac membrane could differentiate into the seawater type independent of
      the embryonic body. To examine the possible effects of exogenous cortisol on
      chloride cell differentiation, the yolk balls were incubated for 48 h in fresh
      water or sea water containing different doses of cortisol (0.1-10 microg x ml(
      1)). Although chloride cells were consistently larger in sea water than in fresh
      water in all experimental groups, cortisol administration had no effect on
      chloride cell surface area in either medium. These findings indicate that the
      chloride cells in the yolk-sac membrane are equipped with an autonomous mechanism
      of functional differentiation that is independent of the embryonic endocrine and
      nervous systems. The yolk-ball incubation system established here is an excellent
      experimental model for further studies on chloride cell differentiation and
      function.

PMID- 11441031
TI  - Dynamics of pavement cell-chloride cell interactions during abrupt salinity
      change in Fundulus heteroclitus.
AB  - Freshwater-adapted killifish (Fundulus heteroclitus) opercular epithelia were
      dissected and subjected to blood-side hypertonic bathing solution in Ussing-style
      chambers to simulate the increase in blood osmolality during migration to sea
      water. Conversely, seawater-acclimated killifish opercular epithelia were
      subjected to hypotonic bathing solutions to simulate the initial stages of
      migration to fresh water. Freshwater-acclimation (hypertonic stress) induced a
      rapid (approximately 30 min) increase in membrane conductance (G(t)) from 3.10+/
      0.56 to 7.52+/-1.15 mS x cm(-2) (P<0.01, N=27), whereas seawater-acclimation
      (hypotonic stress) induced a rapid decrease in G(t) from 8.22+/-1.15 to 4.41+/
      1.00 mS x cm(-2) (P<0.01, N=27; means +/- S.E.M.). Control seawater-acclimated
      membranes had a density of apical crypts (where chloride cells are exposed to the
      environment; detected by scanning electron microscopy) of 1133+/-96.4 crypts x
      mm(-2) (N=12), whereas the hypotonically shocked specimens had a lower crypt
      density of 870+/-36.7 crypts x mm(-2) (P<0.01 N=10; means +/- S.E.M.). Hypertonic
      shock of freshwater membranes increased crypt density from 383.3+/-73.9 (N=12) to
      630+/-102. 9 crypts x mm(-2) (P<0.05; N=11; means +/- S.E.M.). There was no
      change in density of chloride cells, as detected by fluorescence microscopy;
      hence, osmotic stress changes the degree of exposure, not the number of chloride
      cells. Cytochalasin D (5.0 micromol x l(-1)) completely blocked the conductance
      response to hypotonic shock and the reduction in apical crypt density measured by
      scanning electron microscopy, while phalloidin (33 micromol x l(-1)), colchicine
      (3x10(-4)mol x l(-1)) and griseofulvin (1.0 micromol x l(-1)) were ineffective.
      Actin imaging by phalloidin staining and confocal microscopy revealed extensive
      actin cords in pavement cell microridges and a ring of actin at the apex of
      chloride cells. We conclude that the actin cytoskeleton of chloride cells is
      required to maintain crypt opening and that osmotic shock causes chloride cells
      to adjust their apical crypt size.

PMID- 11441032
TI  - Synthesis of the signal molecule acetylcholine during the developmental cycle of
      Paramecium primaurelia (Protista, Ciliophora) and its possible function in
      conjugation.
AB  - We recently discovered, in mating-competent Paramecium primaurelia, the presence
      of functionally related molecules of the cholinergic system: the neurotransmitter
      acetylcholine (ACh), both its nicotinic and muscarinic receptors and its lytic
      enzyme acetylcholinesterase (AChE). Our results on the inhibition of mating-cell
      pairing in vivo in mating-competent cells treated with cholinomimetic drugs
      support the hypothesis that the cholinergic system plays a role in cell-to-cell
      adhesion. To investigate the possible function of the signal molecule ACh in
      conjugation in P. primaurelia, we attempted to detect the intracellular sites of
      ACh synthesis by localizing the ACh biosynthetic enzyme choline acetyltransferase
      (ChAT). Using immunocytochemical and histochemical methods, we have demonstrated
      the presence and activity of ChAT principally on the surface membrane of mating
      competent cells and of mature but non-mating-competent cells. No evidence for
      ChAT activity was found in immature cells. Immunoblot analysis revealed the
      presence of immunoreactive bands, ranging in molecular mass from 42 to 133 kDa,
      as reported for ChAT isolated from higher organisms. In vivo experiments showed
      that inhibition of ChAT activity by Congo Red, known to be a potent competitive
      inhibitor of acetyl coenzyme A, did not affect mating-cell pairing. Conversely,
      inhibition of AChE with BW 284c51 or eserine, which block enzyme activity by
      reacting with a specific serine within the catalytic centre, significantly
      inhibited mating-cell pairing. Our results suggest that ACh has a negative
      modulating effect on conjugation in P. primaurelia.

PMID- 11441033
TI  - Arginine vasotocin modulates a sexually dimorphic communication behavior in the
      weakly electric fish Apteronotus leptorhynchus.
AB  - South American weakly electric fish produce a variety of electric organ discharge
      (EOD) amplitude and frequency modulations including chirps or rapid increases in
      EOD frequency that function as agonistic and courtship and mating displays. In
      Apteronotus leptorhynchus, chirps are readily evoked by the presence of the EOD
      of a conspecific or a sinusoidal signal designed to mimic another EOD, and we
      found that the frequency difference between the discharge of a given animal and
      that of an EOD mimic is important in determining which of two categories of chirp
      an animal will produce. Type-I chirps (EOD frequency increases averaging 650 Hz
      and lasting approximately 25 ms) are preferentially produced by males in response
      to EOD mimics with a frequency of 50-200 Hz higher or lower than that of their
      own. The EOD frequency of Apteronotus leptorhynchus is sexually dimorphic: female
      EODs range from 600 to 800 Hz and male EODs range from 800 to 1000 Hz. Hence, EOD
      frequency differences effective in evoking type-I chirps are most likely to occur
      during male/female interactions. This result supports previous observations that
      type-I chirps are emitted most often during courtship and mating. Type-II chirps,
      which consist of shorter-duration frequency increases of approximately 100 Hz,
      occur preferentially in response to EOD mimics that differ from the EOD of the
      animal by 10-15 Hz. Hence these are preferentially evoked when animals of the
      same sex interact and, as previously suggested, probably represent agonistic
      displays. Females typically produced only type-II chirps. We also investigated
      the effects of arginine vasotocin on chirping. This peptide is known to modulate
      communication and other types of behavior in many species, and we found that
      arginine vasotocin decreased the production of type-II chirps by males and also
      increased the production of type-I chirps in a subset of males. The chirping of
      most females was not significantly affected by arginine vasotocin.

PMID- 11441034
TI  - Limits to sustained energy intake. I. Lactation in the laboratory mouse Mus
      musculus.
AB  - Laboratory mice (strain MF1) were used to determine whether sustainable rates of
      energy intake are limited during lactation. Mice raising natural-sized litters
      (N=71) reached an asymptote in their daily food intake between days 13 and 16 of
      lactation at 23.1 g x day(-1) and also between litter sizes of 9 and 15 pups
      (22.8 g x day(-1)). A second group of 37 females had their litter sizes
      manipulated at birth to raise more or fewer offspring than they gave birth to.
      When the litter size was increased, females did not increase their food intake to
      match their new litter size. However, when litter size was decreased, females
      decreased their asymptotic daily food intake during late lactation in relation to
      the extent of reduction in litter size. Therefore, it appeared that females were
      limited during late lactation and with large litter sizes. The milk energy
      exported amounted to 44% of the gross energy intake, and the estimated daily
      energy expenditure was therefore considerably lower than the sustained energy
      intake [8.0xRMR(gross), 6.6xRMR(assimilated)], and averaged 3.1xRMR, where RMR is
      resting metabolic rate. It was not possible to determine whether the apparent
      limit on sustained energy intake was acting centrally or peripherally because of
      the asymptotes in both food intake and milk energy output with increasing litter
      size.

PMID- 11441035
TI  - Limits to sustained energy intake. II. Inter-relationships between resting
      metabolic rate, life-history traits and morphology in Mus musculus.
AB  - Links between resting metabolic rate (RMR) and reproductive output have been
      previously sought at both inter- and intraspecific levels, but have only been
      found in some interspecific studies. We aimed to examine correlations between RMR
      measured both prior to breeding and at peak lactation with litter size and litter
      mass in Mus musculus. By manipulating the litter size of some females at birth,
      we aimed to establish the direction of causality in any correlation between
      litter size and RMR. Correlations between maternal morphology and RMR, litter
      size and litter mass were also examined. Neither pre-breeding RMR nor mass
      independent pre-breeding RMR was correlated with litter size or litter mass. RMR
      at peak lactation, however, was positively correlated with litter size and
      negatively correlated with mean pup mass. After correcting for the effects of
      body mass, residual peak lactation RMR was not correlated with litter size or
      litter mass. Body size was the major morphological variable influencing litter
      mass, offspring mass and asymptotic food intake. Mammary tissue mass was
      correlated with litter size when only the data for mice raising unmanipulated
      litters were used. RMR at peak lactation was significantly related to the
      principal component of morphology dominated by carcass mass. This study confirms
      the findings of previous intraspecific and some interspecific studies that found
      no correlation between RMR and reproductive output after the effects of body mass
      had been removed.

PMID- 11441036
TI  - Limits to sustained energy intake. III. Effects of concurrent pregnancy and
      lactation in Mus musculus.
AB  - To determine whether mice were limited in their capacity to absorb energy during
      late lactation, we attempted to increase the energy burden experienced by a group
      of female mice during late lactation by mating them at the postpartum oestrus,
      hence combining the energy demands of pregnancy and lactation. These experimental
      mice were therefore concurrently pregnant and lactating in their first lactation,
      and were followed through a normal second lactation. In a control group, females
      also underwent two lactations but sequentially, with the second mating after the
      first litter had been weaned. Maternal mass and food intake were measured
      throughout the first lactation, second pregnancy and second lactation. Maternal
      resting metabolic rate (RMR) was measured prior to the first mating and then at
      the peak of both the first and second lactations. Litter size and litter mass
      were also measured throughout both lactations. In the first lactation,
      experimental mice had a lower mass-independent RMR (F1,88=5.15, P=0.026) and
      raised significantly heavier pups (t=2.77, d.f.=32, P=0.0093) than the control
      mice. Experimental mice delayed implantation at the start of the second
      pregnancy. The extent of the delay was positively related to litter size during
      the first lactation (F1,19=4.58, P=0.046) and negatively related to mean pup mass
      (F1,19=5.78, P=0.027) in the first lactation. In the second lactation, the
      experimental mice gave birth to more (t=2.75, d.f.=38, P=0.0092) and lighter (t=
      5.01, d.f.=38, P<0.0001) pups than did the controls in their second lactation.
      Maternal asymptotic daily food intake of control mice in the second lactation was
      significantly higher (t=-4.39, d.f.=37, P=0.0001) than that of the experimental
      mice and higher than that of controls during their first lactation. Despite the
      added burden on the experimental females during their first lactation, there was
      no increase in their food intake, which suggested that they might be limited by
      their capacity to absorb energy. However, control females appeared to be capable
      of increasing their asymptotic food intake beyond the supposed limits estimated
      previously, suggesting that the previously established limit was not a fixed
      central limitation on food intake. As RMR increased in parallel with the increase
      in food intake during the second lactation of control mice, the sustained energy
      intake remained at around 7.0xRMR.

PMID- 11441037
TI  - Limits to sustained energy intake. IV. Effect of variation in food quality on
      lactating mice Mus musculus.
AB  - Observations were made on 30 MF1 mice with their litters. The animals were fed
      either normal pelleted mouse food (SDS BP Nutrition Ltd) containing 13.4 kJ x g(
      1) digestible energy or a specially formulated diet that provided 25% less
      digestible energy (9.75 kJ x g(-1)) but equivalent amounts of protein and
      essential minerals and vitamins per gram as the normal diet. Half the animals
      were switched to the low-energy diet during early pregnancy and half after
      parturition. The food intake of the two groups increased enormously following
      parturition, reaching an asymptote over the last few days of lactation. In both
      groups, the asymptotic food intake exceeded that previously observed across 71
      litters of this strain of mice fed the normal diet throughout pregnancy and
      lactation; the intake of the group fed the low-energy diet from early lactation
      significantly exceeded that of the mice switched to the low-energy diet after
      parturition. The increased intakes of the experimental groups were, however,
      insufficient to offset the lower digestible energy content of the food during
      lactation. The body mass of the mothers at the end of lactation did not differ
      between the two experimental groups and the controls. Offspring mass at weaning
      was inversely related to litter size, but also did not differ between the three
      groups; pup mortality did not differ between the experimental and control groups.
      Behavioural observations showed that during both the dark and light phases the
      general activity of the mother declined enormously from early pregnancy to late
      lactation. In the dark phase, the time spent in general activity was replaced by
      time spent both feeding and resting (suckling young), but in the light phase it
      was replaced only by feeding. At peak lactation, the mice fed for 30-50% of the
      dark phase and for 30-40% of the light phase. The data indicate that a previously
      observed asymptote in food intake during peak lactation at 23 g x day(-1) is
      unlikely to be a limit mediated centrally by the alimentary tract. A higher
      central limit may exist, at 26.9 g x day(-1), but this is unlikely to reflect the
      time available for feeding. The data are consistent with limits on sustainable
      daily energy intake being mediated by the performance of the mammary glands.
      Animals appeared to accommodate the demands for milk production within a
      constrained total energy budget by compensating their behaviour, most notably by
      reductions in the time spent in 'general activity'.

PMID- 11441038
TI  - Limits to sustained energy intake. V. Effect of cold-exposure during lactation in
      Mus musculus.
AB  - We have previously observed that female MF1 mice appeared to reach a limit in
      their food intake and milk production during late lactation, reaching a plateau
      between days 13 and 16 of lactation and between litter sizes of 9 and 15. These
      mice did not increase their food intake when forced to raise more offspring or
      when manipulated to be concurrently pregnant during late lactation, yet they did
      eat significantly more food at the peak of their second sequential lactation or
      when challenged with food of reduced energy content. These data suggest that
      apparent limits on sustained energy intake in this strain may not reflect central
      limitations but rather peripheral constraints at the mammary glands. In this
      study, we aimed to determine whether these were indeed limits by increasing the
      demands on the females during late lactation by cold-exposure (8 degrees C).
      Females responded to this manipulation by significantly increasing their food
      intake (F1,73=77.53, P<0.001) above that of lactating females kept in warmer
      conditions (21 degrees C). In addition, there was a significant reduction in the
      number of pups raised in the cold (t=2.36, d.f.=18, P=0.03), with the majority of
      the mortality occurring within the first 2 days of cold-exposure. The mean mass
      of the pups raised in the cold was significantly lower (F1,74=13.8, P<0.001) than
      that of those raised in the warm. Despite the cold-exposure and the increased
      food intake, there was no difference in the resting metabolic rates of the two
      groups of mothers or in the lengths of their small intestine. The greater food
      intake of lactating mice during cold-exposure supported our previous observations
      that they were capable of eating more food than the previously suggested limit of
      23.1 g x day(-1). However, the milk energy output of females in the cold was also
      significantly higher than in the warm (F1,15=11.99, P=0.003), indicating that the
      asymptotic food intake of females in the warm was not mediated by limitations in
      their milk production. Sustained energy intake in these mice does not appear to
      be centrally or peripherally limited. Rather, the mice may restrain their use of
      energy during their first lactation because of life-history consequences for
      future reproductive attempts.

PMID- 11441039
TI  - Twisting and bending: the functional role of salamander lateral hypaxial
      musculature during locomotion.
AB  - The function of the lateral hypaxial muscles during locomotion in tetrapods is
      controversial. Currently, there are two hypotheses of lateral hypaxial muscle
      function. The first, supported by electromyographic (EMG) data from a lizard
      (Iguana iguana) and a salamander (Dicamptodon ensatus), suggests that hypaxial
      muscles function to bend the body during swimming and to resist long-axis torsion
      during walking. The second, supported by EMG data from lizards during relatively
      high-speed locomotion, suggests that these muscles function primarily to bend the
      body during locomotion, not to resist torsional forces. To determine whether the
      results from D. ensatus hold for another salamander, we recorded lateral hypaxial
      muscle EMGs synchronized with body and limb kinematics in the tiger salamander
      Ambystoma tigrinum. In agreement with results from aquatic locomotion in D.
      ensatus, all four layers of lateral hypaxial musculature were found to show
      synchronous EMG activity during swimming in A. tigrinum. Our findings for
      terrestrial locomotion also agree with previous results from D. ensatus and
      support the torsion resistance hypothesis for terrestrial locomotion. We observed
      asynchronous EMG bursts of relatively high intensity in the lateral and medial
      pairs of hypaxial muscles during walking in tiger salamanders (we call these
      'alpha-bursts'). We infer from this pattern that the more lateral two layers of
      oblique hypaxial musculature, Mm. obliquus externus superficialis (OES) and
      obliquus externus profundus (OEP), are active on the side towards which the trunk
      is bending, while the more medial two layers, Mm. obliquus internus (OI) and
      transversus abdominis (TA), are active on the opposite side. This result is
      consistent with the hypothesis proposed for D. ensatus that the OES and OEP
      generate torsional moments to counteract ground reaction forces generated by
      forelimb support, while the OI and TA generate torsional moments to counteract
      ground reaction forces from hindlimb support. However, unlike the EMG pattern
      reported for D. ensatus, a second, lower-intensity burst of EMG activity ('beta
      burst') was sometimes recorded from the lateral hypaxial muscles in A. tigrinum.
      As seen in other muscle systems, these beta-bursts of hypaxial muscle
      coactivation may function to provide fine motor control during locomotion. The
      presence of asynchronous, relatively high-intensity alpha-bursts indicates that
      the lateral hypaxial muscles generate torsional moments during terrestrial
      locomotion, but it is possible that the balance of forces from both alpha- and
      beta-bursts may allow the lateral hypaxial muscles to contribute to lateral
      bending of the body as well.

PMID- 11441040
TI  - Effects of altitude and temperature on organ phenotypic plasticity along an
      altitudinal gradient.
AB  - Small mammals living in high-altitude environments must endure decreased ambient
      temperatures and hypoxic conditions relative to sea-level environments.
      Previously, it was noted that heart, lung and digestive tract masses and blood
      hematocrit increase along an altitudinal gradient in small mammals. Increases in
      digestive organ mass were attributed to lower ambient temperatures and greater
      food intake, and increases in lung mass and hematocrit were attributed to
      hypoxia, but these assumptions were not explicitly tested. In addition, it was
      not clear whether changes in heart and lung mass were a function of an increase
      in organ blood content or of an increase in organ tissue mass. We used captive
      deer mice (Peromyscus maniculatus sonoriensis) to determine the relative effects
      of ambient temperature and oxygen concentration (PO2) on organ mass and blood
      hematocrit along an altitudinal gradient. We also exsanguinated hearts and lungs
      to determine whether changes in mass were associated with the blood content or
      with increases in tissue mass. We found that small intestine mass was, as
      expected, correlated positively with energy intake and negatively with ambient
      temperature. Heart mass was also negatively correlated with temperature. Lung
      mass and hematocrit were, as expected, positively correlated with altitude (and
      PO2). Interestingly, the masses of both small intestine and kidney were
      negatively correlated with altitude. For kidney mass, this correlation was
      apparent in cold-exposed mice but not in warm-exposed mice. We also found that
      changes in both heart and lung mass were mainly a function of changes in tissue
      mass rather than blood content. These data show that different abiotic variables
      have different effects on organ masses at high altitude, but also that phenotypic
      plasticity in response to cold temperatures and low oxygen pressures at altitude
      is widespread across several different organ systems, suggesting a general
      elevated whole-body response.

PMID- 11441041
TI  - The salivary adenosine deaminase activity of the mosquitoes Culex
      quinquefasciatus and Aedes aegypti.
AB  - A cDNA coding for a protein with significant similarity to adenosine deaminase
      (ADA) was found while randomly sequencing a cDNA library constructed from
      salivary gland extracts of adult female Culex quinquefasciatus. Prompted by this
      result, we found high ADA activities in two culicine mosquitoes, Culex
      quinquefasciatus and Aedes aegypti, but not in the anopheline Anopheles gambiae.
      Homogenates from Culex quinquefasciatus also have an AMP deaminase activity that
      is three times greater than the ADA activity, whereas in Aedes aegypti the AMP
      deaminase activity is less than 10% of the ADA activity. Evidence for secretion
      of ADA during blood feeding by Aedes aegypti includes the presence of ADA
      activity in warm solutions probed through a membrane by mosquitoes and in
      serotonin-induced saliva and a statistically significant reduction in the levels
      of the enzyme in Aedes aegypti following a blood meal. We could not demonstrate,
      however, that C. quinquefasciatus secrete ADA in their saliva. Male Aedes aegypti
      and C. quinquefasciatus, which do not feed on blood, have less than 3% of the
      levels of ADA found in females. We propose that ADA activity in A. aegypti may
      help blood feeding by removing adenosine, a molecule associated with both the
      initiation of pain perception and the induction of mast cell degranulation in
      vertebrates, and by producing inosine, a molecule that potently inhibits the
      production of inflammatory cytokines. The role of salivary ADA in Culex
      quinquefasciatus remains unclear.

PMID- 11441042
TI  - N-acetylneuraminic acid (NANA) stimulates in situ cyclic AMP production in
      tentacles of sea anemone (Aiptasia pallida): possible role in chemosensitization
      of nematocyst discharge.
AB  - Cnidocytes, the stinging cells of cnidarians, optimally discharge nematocysts in
      response to combined physical contact and stimulation of specific chemoreceptors.
      In the tentacles of certain sea anemones, the primary chemoreceptors bind N
      acetylated sugars, such as N-acetylneuraminic acid (NANA). Sensitization with
      NANA predisposes contact-sensitive mechanoreceptors (CSMs) to trigger discharge
      in response to physical contact. In the ectoderm of sea anemone tentacles,
      cnidocyte/supporting cell complexes (CSCCs) control and trigger nematocyst
      discharge. Previous findings have implicated cyclic AMP (cAMP) as a second
      messenger in NANA-sensitized nematocyst discharge. However, no reports have
      directly demonstrated that the cAMP content of tentacles changes in response to
      NANA stimulation. We now show that NANA elevates in situ cAMP levels in a dose
      dependent manner in the ectoderm of tentacles from the sea anemone Aiptasia
      pallida. However, the endoderm of tentacles shows no detectable cAMP response to
      NANA. The effect of NANA on the cAMP content of the ectoderm is biphasic.
      Micromolar NANA increases the in situ cAMP level, with a maximal response
      occurring at 1.8x10(-5)mol x l(-1) NANA. At higher NANA concentrations, the cAMP
      content decreases to that of controls. Because the cAMP dose/response curve to
      NANA coincides precisely with the dose/response curves of NANA-sensitized
      nematocyst discharge and nematocyst-mediated adhesive force, a second-messenger
      role for cAMP in NANA-sensitized nematocyst discharge is strongly suggested. The
      addition of isobutyl-1-methylxanthine (IBMX) to the medium with sea anemones
      increases tissue cAMP levels both in the absence and in the presence of NANA.
      However, anesthetizing anemones in sea water containing high levels of Mg(2+)
      blocks the NANA-stimulated cAMP response of the ectoderm. In addition, our
      results suggest that NANA-stimulated cAMP may activate endogenous cAMP-dependent
      protein kinase (PKA) in broken cell preparations of tentacles. Thus, NANA
      stimulated cAMP may function as a second messenger in the NANA chemosensory
      signaling pathway controlling nematocyst discharge.

PMID- 11441043
TI  - Hovering performance of hummingbirds in hyperoxic gas mixtures.
AB  - Hummingbirds evolved during a period of decline in atmospheric oxygen
      concentration and currently encounter varying levels of oxygen availability along
      their elevational distribution. We tested the hypothesis that inspiration of
      hyperoxic gas increases hummingbird hovering performance when birds are
      simultaneously challenged aerodynamically. We measured the maximum duration of
      hovering flight while simultaneously monitoring the rate of oxygen consumption of
      ruby-throated hummingbirds (Archilochus colubris) in low-density heliox that was
      either normoxic (21% O2) or hyperoxic (35% O2). As air density decreased below
      0.85 kg x m(-3), hummingbirds hovered significantly longer in hyperoxia than in
      normoxia, but the air density at which the birds could no longer sustain hovering
      flight was independent of oxygen concentration. At low air densities in hyperoxia
      flight trials, hummingbirds appeared to increase their rate of oxygen consumption
      relative to flight sequences at equivalent densities in normoxia trials, but
      these differences were not significant. We tested the hypothesis that
      hummingbirds can discriminate between environments that differ in oxygen
      concentration. In another density-reduction experiment, hummingbirds were allowed
      to choose between artificial feeders infused with either normoxic or hyperoxic
      gases. The hypothesis was not supported because birds failed to associate oxygen
      concentration with a particular feeder independently of air density. Supplemental
      oxygen thus yields increased hovering duration at intermediate air densities, but
      the minimum density at which birds can fly is limited exclusively by aerodynamic
      considerations.

PMID- 11441044
TI  - Comparative analysis of autoxidation of haemoglobin.
AB  - Autoxidation of oxyhaemoglobin (oxyHb) to methaemoglobin was measured at
      different temperatures in haemoglobin solutions from Atlantic hagfish, river
      lamprey, common carp, yellowfin tuna and pig. The aims were to evaluate the
      impact of the absent distal histidine in hagfish haemoglobin, the importance of
      oxyHb being either monomeric (hagfish and lamprey) or tetrameric (carp, tuna and
      pig) and to gain information on the temperature-sensitivity of autoxidation. The
      rate of autoxidation was lower in hagfish than in carp, yellowfin tuna and
      lamprey haemoglobins at any given temperature. Substitution of the distal
      histidine residue (His E7) with glutamine in hagfish haemoglobin was therefore
      not associated with an accelerated autoxidation, as might be expected on the
      basis of the normal protective role of His E7. Glutamine may have similar
      qualities to histidine and be involved in the low susceptibility to autoxidation.
      The low oxidation rate of hagfish haemoglobin, together with an oxidation rate of
      lamprey haemoglobin that did not differ from that of carp and yellowfin tuna
      haemoglobins, also revealed that autoxidation was not accelerated in the
      monomeric oxyhaemoglobins. Pig haemoglobin was oxidised more slowly than fish
      haemoglobins, demonstrating that fish haemoglobins are more sensitive to
      autoxidation than mammalian haemoglobins. The rate of autoxidation of hagfish
      haemoglobin was, however, only significantly greater than that of pig haemoglobin
      at high temperatures. Autoxidation was accelerated by rising temperature in all
      haemoglobins. Arrhenius plots of carp and yellowfin tuna haemoglobin revealed a
      break at 25 degrees C, reflecting a lower temperature-sensitivity between 5 and
      25 degrees C than between 25 and 40 degrees C.

PMID- 11441046
TI  - Neuropeptides are ubiquitous chemical mediators: Using the stomatogastric nervous
      system as a model system.
AB  - The stomatogastric nervous system (STNS) controls the movements of the foregut
      and the oesophagus of decapod crustaceans and is a good example for demonstrating
      that peptides are ubiquitously distributed chemical mediators in the nervous
      system. The stomatogastric ganglion (STG), one of the four ganglia of the STNS,
      contains the most intensively investigated neuronal circuits. The other ganglia,
      including the two commissural ganglia (CoGs) and the oesophageal ganglion (OG),
      are thought to be modulatory control centres. Peptides reach the STNS either as
      neurohormones or are released as transmitters. Peptide neurohormones can be
      released either from neurohaemal organs or from local neurohaemal release zones
      located on the surface of nerves and connectives. There were thought to be no
      peptidergic neurones with cell bodies in the STG itself. However, some have
      recently been described in adults of four species, in addition to a transient
      expression of peptides during development in two species. None of these
      peptidergic neurones has been investigated physiologically, in contrast to
      peptidergic neurones that project to the STG and have cell bodies in either the
      CoGs or the OG. It has been shown that neurones containing the same peptide
      elicit different motor patterns, that the peptide transmitter and the classical
      transmitter are not necessarily co-released and that the effect of a peptidergic
      neurone depends on its firing frequency and on which other modulatory neurones
      are co-active. The activity of modulatory projection neurones can be elicited by
      sensory neurones, and their activity can depend on the firing frequency of the
      sensory neurone. In addition to being found within the neuropile of ganglia,
      peptides are present in neuropile patches located within the nerves of the STNS,
      suggesting that these nerves can integrate as well as transfer information.
      Furthermore, sensory neurones and muscles exhibit peptide-like immunoreactivity
      and are modulated by peptides. Bath-applied peptides elicit peptide-specific
      motor patterns within the STG by targeting subsets of neurones. This divergence
      is contrasted by a convergence at the level of currents: five different peptides
      modulate a single current. Peptides not only induce motor patterns but can also
      switch the alliance of neurones from one network to another or are able to fuse
      different networks. In general, peptides are the most abundant group of
      modulators within the STNS; they are ubiquitously present, indicating that they
      play multiple roles in the plasticity of neural networks.

PMID- 11441047
TI  - Differential and overlapping expression patterns of X-dll3 and Pax-6 genes
      suggest distinct roles in olfactory system development of the African clawed frog
      Xenopus laevis.
AB  - In Xenopus laevis, the formation of the adult olfactory epithelium involves
      embryonic, larval and metamorphic phases. The olfactory epithelium in the
      principal cavity (PC) develops during embryogenesis from the olfactory placode
      and is thought to respond to water-borne odorants throughout larval life. During
      metamorphosis, the PC undergoes major transformations and is exposed to air-borne
      odorants. Also during metamorphosis, the middle cavity (MC) develops de novo. The
      olfactory epithelium in the MC has the same characteristics as that in the larval
      PC and is thought to respond to water-borne odorants. Using in situ
      hybridization, we analyzed the expression pattern of the homeobox genes X-dll3
      and Pax-6 within the developing olfactory system. Early in development, X-dll3 is
      expressed in both the neuronal and non-neuronal ectoderm of the sense plate and
      in all cell layers of the olfactory placode and larval PC. Expression becomes
      restricted to the neurons and basal cells of the PC by mid-metamorphosis. During
      metamorphosis, X-dll3 is also expressed throughout the developing MC epithelium
      and becomes restricted to neurons and basal cells at metamorphic climax. This
      expression pattern suggests that X-dll3 is first involved in the patterning and
      genesis of all cells forming the olfactory tissue and is then involved in
      neurogenesis or neuronal maturation in putative water- and air-sensing epithelia.
      In contrast, Pax-6 expression is restricted to the olfactory placode, larval PC
      and metamorphic MC, suggesting that Pax-6 is specifically involved in the
      formation of water-sensing epithelium. The expression patterns suggest that X
      dll3 and Pax-6 are both involved in establishing the olfactory placode during
      embryonic development, but subtle differences in cellular and temporal expression
      patterns suggest that these genes have distinct functions.

PMID- 11441048
TI  - Homing in wood ants, Formica japonica: use of the skyline panorama.
AB  - Homeward orientation was studied in wood ants Formica japonica that, while
      foraging, shuttled back and forth along a 7.9m route between the nest and a
      feeding site located on a wide terrace platform surrounded by a conspicuous
      landmark panorama. The return runs of the ants were amazingly straight, not only
      in the controls (starting at the feeding site) but also in ants displaced for
      various distances to the left and right of the feeding site. These courses,
      however, were oriented neither parallel to the predisplacement courses nor
      directly towards the nest. This result excludes the use of chemical cues and
      celestial compass cues. Furthermore, the nest itself, or some object close to it,
      could not have served as a beacon. The extensions of the homeward paths taken by
      ants that had been displaced to various release sites up to 11m sideways from the
      training route intersected at a point far (approximately 13m) behind the nest.
      This result suggests that the ants used distant landmarks seen by them in their
      frontal fields of view. To test this hypothesis, the distant landmark panorama
      was concealed by an opaque sheet mounted at right angles to the normal return
      route of the ants and extending up to different elevations. Shielding the lower
      part of the landmark panorama had no effect on the homeward paths. However, when
      the screen was mounted in such a way that the ants could only see the top
      skyline, represented by the upper edges of a line of trees, for part of their
      return run, it was only during these parts that their path was oriented in the
      homeward direction. When, during the course of displacement experiments, the ants
      were deprived of their familiar skyline panorama, they moved in their home
      direction only for an extremely short distance (0.1-0.4m rather than the usual
      7.9m) and then started a systematic search programme. Hence, in the present
      context, skylight information is not used, at least not extensively. Instead,
      ants use the distant skyline as a navigational guidemark.

PMID- 11441049
TI  - Shape, flapping and flexion: wing and fin design for forward flight.
AB  - Both kinematics and morphology are critical determinants of performance in
      flapping flight. However, the functional consequences of changes in these traits
      are not yet well understood. Traditional aerodynamic studies of planform wing
      shape have suggested that high-aspect-ratio wings generate more force per area
      and perform more efficiently than low-aspect-ratio wings, but these analyses may
      neglect critical components of flapping flight such as unsteady fluid dynamics
      and wing or fin flexion. In this paper, we use an unsteady potential flow
      analysis that incorporates wing flexion to test predictions of optimal wing shape
      under varying degrees of unsteady motion and wing flexion. We focus on forward
      flapping flight and examine the effects of wing/fin morphology and movements on
      thrust generation and efficiency. We test the model by comparing our predictions
      with kinematic data derived from the aquatic flight of the ratfish Hydrolagus
      colliei. Our analyses show that aspect ratio and the proportion of area in the
      outer one-fifth of the wing can characterize wing shape in terms of aero- or
      hydrodynamic performance. By comparing the performance of wings that vary in
      these two parameters, we find that traditional predictions of optimal wing shape
      are valid only under limited circumstances (when flapping frequency is low, wings
      are stiff or wings are tapered at the tips). This indicates a complex
      relationship between locomotor traits and performance and helps explain the
      diversity of wing kinematics and morphologies observed in nature.

PMID- 11441050
TI  - Expression and function of brain-derived neurotrophin factor and its receptor,
      TrkB, in ovarian follicles from the domestic hen (Gallus gallus domesticus).
AB  - This report summarizes patterns of mRNA expression for the brain-derived
      neurotrophic factor (BDNF) together with its high-affinity neurotrophin receptor
      trkB within the hen ovary during follicle development, describes hormonal
      mechanisms for the regulation of trkB gene expression and provides preliminary
      evidence for a novel function for BDNF-mediated TrkB signaling within the
      granulosa layer. Levels of BDNF mRNA in the thecal layer and of trkB mRNA within
      the granulosa cell layer increase coincident with entrance of the follicle into
      the preovulatory hierarchy. Localization of the BDNF mRNA transcript correlates
      with expression of BDNF protein within the theca interna of preovulatory
      follicles, while localization of trkB mRNA and protein occurs extensively within
      the granulosa cell layer of preovulatory follicles. This pattern of expression
      suggests a paracrine relationship between theca and granulosa cells for BDNF
      signaling via TrkB. Vasoactive intestinal peptide and gonadotropin treatments
      stimulate increases in levels of trkB mRNA within cultured granulosa cells
      derived from both prehierarchal and preovulatory follicles, and this response is
      increased by co-treatment with 3-isobutyl-1-methylxanthine. Finally, BDNF
      treatment of cultured granulosa cells from preovulatory follicles results in a
      modest, but significant, reduction in basal progesterone production, whereas this
      effect was reversed by k252a, an inhibitor of Trk kinase activity. These results
      support the proposals that BDNF functions as a paracrine signal in hen granulosa
      cells and that its physiological functions may include the modulation of
      steroidogenesis.

PMID- 11441051
TI  - Red and white muscle development in the trout (Oncorhynchus mykiss) as shown by
      in situ hybridisation of fast and slow myosin heavy chain transcripts.
AB  - The axial muscle of most teleost species consists of a deep bulk of fast
      contracting white fibres and a superficial strip of slow-contracting red fibres.
      To investigate the embryological development of fast and slow muscle in trout
      embryos, we carried out single and double in situ hybridisation with fast and
      slow myosin heavy chain (MyHC)-isoform-specific riboprobes. This showed that the
      slow-MyHC-positive cells originate in a region of the somite close to the
      notochord. As the somite matures in a rostrocaudal progression, the slow-MyHC
      positive cells appear to migrate radially away from the notochord to the lateral
      surface of the myotome, where they form the superficial strip of slow muscle.
      Surprisingly, the expression pattern of the fast MyHC showed that the
      differentiation of fast muscle commences in the medial domain of the somite
      before the differentiation and migration of the slow muscle precursors. Later, as
      the differentiation of fast muscle progressively spreads from the inside to the
      outside of the myotome, slow-MyHC-expressing cells become visible medially. Our
      observations that the initial differentiation of fast muscle takes place in
      proximity to axial structures and occurs before the differentiation and migration
      of slow muscle progenitors are not in accord with the pattern of muscle formation
      in teleosts previously described in the zebrafish Danio rerio, which is often
      used as the model organism in fishes.

PMID- 11441052
TI  - Reflective properties of iridophores and fluorescent 'eyespots' in the loliginid
      squid Alloteuthis subulata and Loligo vulgaris.
AB  - Observations were made of the reflective properties of the iridophore stripes of
      the squid Alloteuthis subulata and Loligo vulgaris, and the likely functions of
      these stripes are considered in terms of concealment and signalling. In both
      species, the mantle muscle is almost transparent. Stripes of iridophores run
      along the length of each side of the mantle, some of which, when viewed at normal
      incidence in white light, reflect red, others green or blue. When viewed
      obliquely, the wavebands best reflected move towards the blue/ultraviolet end of
      the spectrum and their reflections are almost 100% polarised. These are
      properties of quarter-wavelength stacks of chitin and cytoplasm, predicted in
      theoretical analyses made by Sir A. F. Huxley and Professor M. F. Land. The
      reflecting surfaces of the individual iridophores are almost flat and, in a given
      stripe, these surfaces are within a few degrees of being parallel. Both species
      of squid have conspicuous, brightly coloured reflectors above their eyes. These
      'eyespots' have iridescent layers similar to those found on the mantle but are
      overlaid by a green fluorescent layer that does not change colour or become
      polarised as it is viewed more obliquely. In the sea, all reflections from the
      iridophore stripes will be largely confined to the blue-green parts of the
      spectrum and all reflections in other wavebands, such as those in the red and
      near ultraviolet, will be weak. The functions of the iridophores reflecting red
      at normal incidence must be sought in their reflections of blue-green at oblique
      angles of incidence. These squid rely for their camouflage mainly on their
      transparency, and the ventral iridophores and the red, green and blue reflective
      stripes must be used mainly for signalling. The reflectivities of some of these
      stripes are relatively low, allowing a large fraction of the incident light to be
      transmitted into the mantle cavity. Despite their low reflectivities, the stripes
      are very conspicuous when viewed from some limited directions because they
      reflect light from directions for which the radiances are much higher than those
      of the backgrounds against which they are viewed. The reflective patterns seen,
      for example, by neighbouring squid when schooling depend on the orientation of
      the squid in the external light field and the position of the squid relative to
      these neighbours.

PMID- 11441053
TI  - Cuttlefish camouflage: visual perception of size, contrast and number of white
      squares on artificial checkerboard substrata initiates disruptive coloration.
AB  - We investigated some visual background features that influence young cuttlefish,
      Sepia pharaonis, to change their skin patterning from 'general resemblance' of
      the substratum to disruptive coloration that breaks up their body form. Using
      computer-generated black/white checkerboard patterns as substrata, we first found
      that the size of the white squares had to be within a certain narrow range
      (relative to the size of the cuttlefish 'white square') for the animal to exhibit
      disruptive skin patterning. Second, given the appropriate size of checker,
      cuttlefish regulated their disruptive skin patterns according to the contrast
      between white and black squares. Third, by manipulating the number of white
      squares on a black background, we found that as few as four white squares among
      316 black squares (or 1.25%) produced disruptive patterning, yet increasing the
      number of white squares to 20, 40 or 80 did not increase the frequency of
      appearance of the cuttlefish 'white square', but only its clarity of expression.
      These results demonstrate that the size, contrast and number of white objects in
      the surrounding substratum influence the production and expression of disruptive
      skin patterns in young cuttlefish.

PMID- 11441054
TI  - Postprandial exercise: prioritization or additivity of the metabolic responses?
AB  - Monitor lizards (Varanus exanthematicus) were used to examine the prioritization
      or additivity of the metabolic responses associated with exercise and digestion,
      either of which can elevate metabolic rate independently. Rates of oxygen
      consumption (V(O2)) and ventilation (V(E)) were measured in lizards during
      fasting exercise, postprandial rest and postprandial exercise. In fasting
      animals, V(O2) increased with walking speed to a maximal value of 15.9 ml O(2)kg(
      1)min(-1) at 1.25 km h(-1). Postprandial resting metabolic rate was elevated
      significantly above fasting levels (4.1 versus 2.0 ml O(2)kg(-1)min(-1)). During
      postprandial exercise, V(O2) increased to a maximal value of 18.8 ml O(2)kg(
      1)min(-1) at 1.25 km h(-1). At every level of exercise, V(O2) was significantly
      higher in postprandial animals by a similar increment; the maximal rate of oxygen
      consumption was significantly increased by 18% in postprandial individuals.
      Maximal V(E) did not differ in fasting and postprandial animals and, therefore,
      the greater V(O2)(max) of postprandial animals cannot be attributed to a higher
      ventilation rate. Air convection requirement (V(E)/V(O2)) is significantly lower
      in postprandial animals at rest and at all levels of exercise, indicating a
      relative hypoventilation and increased pulmonary oxygen extraction efficiency. We
      suggest that this increased oxygen extraction may be due to decreased
      cardiopulmonary shunts and/or to lower mixed venous oxygen content. The data
      unequivocally support an additivity model rather than prioritization models for
      the allocation of elevated metabolic rate: the postprandial metabolic increment
      is not suspended during exercise, but rather is added onto the cost of exercise.
      It is clear that fasting exercise did not elicit truly maximal levels of
      cardiopulmonary oxygen transport in these animals, indicating problems for design
      models that make this assumption.

PMID- 11441055
TI  - Heart rate as an indicator of oxygen consumption: influence of body condition in
      the king penguin.
AB  - The use of heart rate to estimate field metabolic rate has become a more widely
      used technique. However, this method also has some limitations, among which is
      the possible impact that several variables such as sex, body condition (i.e. body
      fat stores) and/or inactivity might have on the relationship between heart rate
      and rate of oxygen consumption. In the present study, we investigate the extent
      to which body condition can affect the use of heart rate as an indicator of the
      rate of oxygen consumption. Twenty-two breeding king penguins (Aptenodytes
      patagonicus) were exercised on a variable-speed treadmill. These birds were
      allocated to four groups according to their sex and whether or not they had been
      fasting. Linear regression equations were used to describe the relationship
      between heart rate and the rate of oxygen consumption for each group. There were
      significant differences between the regression equations for the four groups.
      Good relationships were obtained between resting and active oxygen pulses and an
      index of the body condition of the birds. Validation experiments on six courting
      king penguins showed that the use of a combination of resting oxygen pulse and
      active oxygen pulse gave the best estimate of the rate of oxygen consumption
      V(O2). The mean percentage error between predicted and measured V(O2) was only
      +0.81% for the six birds. We conclude that heart rate can be used to estimate
      rate of oxygen consumption in free-ranging king penguins even over a small time
      scale (30 min). However, (i) the type of activity of the bird must be known and
      (ii) the body condition of the bird must be accurately determined. More
      investigations on the impact of fasting and/or inactivity on this relationship
      are required to refine these estimates further.

PMID- 11441056
TI  - Ammonia detoxification and localization of urea cycle enzyme activity in embryos
      of the rainbow trout (Oncorhynchus mykiss) in relation to early tolerance to high
      environmental ammonia levels.
AB  - The present study investigated the role of ammonia as a trigger for hatching,
      mechanisms of ammonia detoxification and the localization of urea cycle enzymes
      in the early life stages of freshwater rainbow trout (Oncorhynchus mykiss). The
      key urea cycle enzyme carbamoyl phosphate synthetase III was found exclusively in
      the embryonic body (non-hepatic tissues); related enzymes were distributed
      between the liver and embryonic body. 'Eyed-up' trout embryos were exposed either
      acutely (2h) to 10 mmol l(-1) NH(4)Cl or chronically (4 days) to 0.2 mmol l(-1)
      NH(4)Cl. Time to hatching was not affected by either acute or chronic NH(4)Cl
      exposure. Urea levels, but not ammonia levels in the embryonic tissues, were
      significantly higher than in controls after both acute and chronic NH(4)Cl
      exposure, whereas there were no significant changes in urea cycle enzyme
      activities. Total amino acid levels in the embryonic tissues were unaltered by
      chronic ammonia exposure, but levels of most individual amino acids and total
      amino acid levels in the yolk were significantly lower (by 34-58%) than in non
      exposed controls. The data indicate that trout embryos have an efficient system
      to prevent ammonia accumulation in embryonic tissue, by conversion of ammonia to
      urea in embryonic tissues and through elevation of ammonia levels in the yolk.

PMID- 11441057
TI  - Pathways for urea production during early life of an air-breathing teleost, the
      African catfish Clarias gariepinus Burchell.
AB  - Embryos and larvae of the African catfish Clarias gariepinus excrete significant
      quantities of urea. The present study focused on the potential urea-generating
      pathways during early development of this teleost; uricolysis, argininolysis and
      the ornithine-urea cycle (OUC). Uricase, allantoinase, allantoicase and
      ureidoglycollate lyase of the uricolytic pathway were expressed in all early life
      stages and in adult liver of C. gariepinus. Uricase activity increased in starved
      larvae compared with yolk-sac larvae. The key regulatory enzyme of the teleost
      OUC, carbamoyl phosphate synthetase III (CPSase III), was expressed predominantly
      in muscle of developing C. gariepinus larvae and showed negligible activity in
      the absence of its allosteric effector N-acetyl-L-glutamate. CPSase III and
      ornithine carbamoyl transferase activities increased in fed larvae compared with
      starved larvae. In contrast to the early developmental stages, adult C.
      gariepinus expressed only low and variable levels of CPSase III, suggesting that,
      under the experimental conditions employed, OUC expression is influenced by
      developmental stage in this species. The data indicate that early C. gariepinus
      life stages express the enzymes necessary for urea production by uricolysis,
      argininolysis and the OUC, and this may explain why urea tissue levels and urea
      excretion rates are substantial during the early development of this air
      breathing teleost.

PMID- 11441058
TI  - Time course and reversibility of changes in the gizzards of red knots alternately
      eating hard and soft food.
AB  - The ability to change organ size reversibly can be advantageous to birds that
      perform long migrations. During winter, red knots (Calidris canutus) feed on
      shellfish and carry a muscular gizzard that weighs 10% of their body mass.
      Gizzard size decreases when these birds eat soft foods, e.g. while breeding in
      the tundra. We studied the reversibility and time course of such changes using
      ultrasonography. Two groups of shellfish-adapted knots (N=9 and N=10) were fed
      alternately a hard and a soft food type. Diet switches elicited rapid reversible
      changes. Switches from hard to soft food induced decreases to 60% of initial
      gizzard mass within 8.5 days, while switches to hard food induced increases in
      gizzard mass to 147% within 6.2 days. A third group of knots (N=11), adapted to
      soft food for more than 1 year, initially had very small gizzards (25% of the
      mass of shellfish-adapted gizzards), but showed a similar capacity to increase
      gizzard size when fed shellfish. This is the first non-invasive study showing
      rapid digestive organ adjustments in non-domesticated birds.

PMID- 11441059
TI  - Comparative energetics during early development of two marine fish species, Solea
      senegalensis (Kaup) and Sparus aurata (L.).
AB  - Growth, energy content, ingestion and respiration rates and energetic
      efficiencies were measured in the larvae of two marine fish (Solea senegalensis
      and Sparus aurata) whose eggs have a similar diameter (approximately 1mm) and
      energy content (approximately 1J), but whose larvae reach a quite different mass
      after the first month of life. Experiments were carried out in populations reared
      under the same conditions in the laboratory during the first month after
      hatching. Solea senegalensis grow from hatching to the start of metamorphosis
      (approximately day 14) at twice the rate of Sparus aurata (specific growth rate
      for Solea senegalensis 0.25 microg day(-1); specific growth rate for Sparus
      aurata 0.12 microg day(-1)). The tissues in Solea senegalensis larvae accumulated
      energetic reserves that were used during metamorphosis, which occurred during the
      third week after hatching. Ingestion and respiration rates differed in the two
      species during the experimental period. Although Solea senegalensis continued
      eating during metamorphosis, the specific ingestion rates decreased during the
      process. Nevertheless, no great differences in specific ingestion rates and rates
      of oxygen consumption were observed when comparing the same larval mass range.
      Larvae of both species showed an allometric relationship between respiration rate
      and biomass. The energetic efficiencies calculated in the present study denoted
      different metabolic patterns in each species. In Solea senegalensis, the energy
      used for growth increased progressively during the larval (pelagic) period and
      then, from the first signs of metamorphic transformation, remained almost
      constant. In this species, the energy allocated to growth was greater than that
      allocated to metabolic processes. Sparus aurata invested less energy in growth
      than in metabolic processes and displayed a constant energy allocation throughout
      the experimental period. During the first month after hatching, Solea
      senegalensis always allocated more energy for growth than did Sparus aurata.

PMID- 11441060
TI  - Effects of temperature and aquatic P(O2) on the physiology and behaviour of
      Apalone ferox and Chrysemys picta.
AB  - Softshell turtles overwinter in the same bodies of water as some emydids, but
      their reduced shell and increased non-pulmonary gas exchange may contribute to a
      different mechanism of overwintering. The dynamics of bimodal respiration, diving
      behaviour and blood acid-base status in Apalone ferox and Chrysemys picta were
      investigated under two different temperatures combined with three different
      aquatic P(O2) levels. Both species obtained oxygen through pulmonary and non
      pulmonary routes. Apalone ferox obtained more oxygen through non-pulmonary routes
      and increased its non-pulmonary V(O2) in response to both higher aquatic P(O2)
      and lower temperatures. Both species increased pulmonary V(O2) in response to
      higher temperatures. As a consequence of the greater reliance of A. ferox on
      pulmonary V(O2), warmer temperatures caused plasma P(CO2) and [HCO(3)(-1)] values
      to increase significantly compared with C. picta. Apalone ferox, which is
      efficient at bimodal respiration, displayed a high degree of plasticity with
      respect to both its respiratory and acid-base profiles, behaving more like an
      aquatic air-breathing fish in bimodal respiration at low temperature and more
      like a terrestrial air-breather at high temperature. Chrysemys picta, which is
      poor at bimodal respiration, was highly dependent on aerial gas exchange at both
      temperatures. Aquatic P(O2) did not change any of the behavioural variables
      measured. At warm temperatures, A. ferox met O(2) demands by increasing the rate
      of lung ventilation, which resulted in a significantly greater number of
      breathing bouts per hour and breaths per emersion period. However, the number of
      breaths per bout was not affected by temperature. As temperatures decreased, A.
      ferox utilized its non-pulmonary respiration ability and significantly increased
      its dive duration. Apalone ferox became less active at colder temperatures by
      significantly increasing the duration of inactive periods (from 4 to 18 min) and
      by significantly decreasing the frequency of activity bursts. Chrysemys picta
      also met the higher gas-exchange demands associated with increased temperature by
      increasing the rate of lung ventilation; however, this increase was not as large
      as that measured in A. ferox. Chrysemys picta displayed multiple rhythmic breaths
      per bout. These results indicate that, unlike aquatic P(O2), temperature is an
      important factor in the regulation of diving and ventilatory behaviour in
      turtles. The species responded to temperature in dissimilar ways because of
      differences in their bimodal respiration ability.

PMID- 11441061
TI  - Major histocompatibility complex proteins and TCRs: do they really go together
      like a horse and carriage?

PMID- 11441062
TI  - Cutting edge: IFN-inducible ELR- CXC chemokines display defensin-like
      antimicrobial activity.
AB  - Recent reports highlighted the chemotactic activities of antimicrobial peptide
      defensins whose structure, charge, and size resemble chemokines. By assaying
      representative members of the four known families of chemokines we explored the
      obverse: whether some chemokines exert antimicrobial activity. In a radial
      diffusion assay, only recombinant monokine induced by IFN-gamma (MIG/CXCL9), IFN
      gamma-inducible protein of 10 kDa (IP-10/CXCL10), and IFN-inducible T cell alpha
      chemoattractant (I-TAC/CXCL11), members of the IFN-gamma-inducible tripeptide
      motif Glu-Leu-Arg (ELR)(-) CXC chemokines, were antimicrobial against Escherichia
      coli and Listeria monocytogenes. Similar to human defensins, antimicrobial
      activities of the chemokines were inhibited by 50 and 100 mM NaCl. The
      concentration of MIG/CXCL9 and IP-10/CXCL10 released from IFN-gamma-stimulated
      PBMC in 24 h were, respectively, 35- and 28-fold higher than from unstimulated
      cells. Additionally, the amounts of chemokines released per monocyte suggest
      that, in tissues with mononuclear cell infiltration, IFN-gamma-inducible
      chemokines may reach concentrations necessary for microbicidal activity. IFN
      gamma-inducible chemokines may directly inactivate microbes before attracting
      other host defense cells to the area of infection.

PMID- 11441063
TI  - Cutting edge: differential requirements for Stat4 in expression of
      glycosyltransferases responsible for selectin ligand formation in Th1 cells.
AB  - A role for Stat4 in IL-12-induced up-regulation of selectin ligands on Th1 cells
      was explored. Th1 cells generated from Stat4(-/-) mice exhibited no IL-12
      inducible P-selectin ligands, no up-regulation of core 2 beta1,6
      glucosaminyltransferase I (C2GlcNAcT-I), and low levels of the Th1 transcription
      factor T-bet. In contrast, Stat4(-/-) Th1 cells exhibited only a partial defect
      in expression of IL-12-inducible E-selectin ligands and expressed equivalently
      high levels of alpha1,3-fucosyltransferase VII (FucT-VII) as wild-type Th1 cells.
      FucT-VII expression was induced by T cell activation, and was enhanced by IL-12
      independently of Stat4, whereas C2GlcNAcT-I up-regulation was mediated
      exclusively by IL-12, acting through Stat4. These data show that FucT-VII and
      C2GlcNAcT-I are controlled through distinct pathways and imply the existence of
      at least one other IL-12-inducible glycosyltransferase required for E-selectin
      and possibly P-selectin ligand formation in Th1 cells.

PMID- 11441064
TI  - Cutting edge: editing of recycling class II:peptide complexes by HLA-DM.
AB  - HLA-DM catalyzes the exchange and selection of ligands for MHC class II molecules
      within mature endosomal/lysosomal compartments. Here, evidence is provided that
      DM edits peptides in early endosomes, thus influencing presentation via recycling
      class II molecules. Maximal class II-restricted presentation of an albumin
      derived peptide, dependent on endocytosis and recycling class II molecules, was
      observed in cells lacking HLA-DM. DM editing of this epitope was observed in
      early endocytic compartments as shown using inhibitors of early to late endosomal
      transport. Editing was tempered by coexpression of HLA-DO, suggesting that DM:DO
      ratio may be important in guiding epitope editing in early endosomal
      compartments. Thus, HLA-DM appears to interact with, and edit epitopes displayed
      by, recycling class II molecules.

PMID- 11441065
TI  - Cutting edge: protein kinase C beta expression is critical for export of Il-2
      from T cells.
AB  - Protein kinase C (PKC) plays an integral part in T cell activation and IL-2
      secretion. We investigated the role of a particular PKC isoform, PKCbeta, in IL-2
      production and secretion. The T cell lymphoma line HuT 78 secretes IL-2 in
      response to the phorbol ester PMA. A PKCbeta-deficient clone of HuT 78, K-4, did
      not secrete IL-2 in response to PMA stimulation. As assessed by RT-PCR, K-4
      expressed mRNA for IL-2 following PMA activation, and intracellular IL-2 protein
      was detected by immunofluorescence. An enhanced green fluorescent protein-linked
      PKCbeta construct was microinjected into K-4 cells, which were then stimulated
      with PMA; those cells that expressed PKCbeta could secrete IL-2, as determined by
      an in situ immunofluorescent assay. This study demonstrates that PKCbeta is not
      necessary for transcription of the IL-2 gene or translation of mRNA to protein,
      but that expression of this PKC isoform is critical to the export of IL-2
      molecules from T cells.

PMID- 11441066
TI  - Cutting edge: integration of human T lymphocyte cytoskeleton by the cytolinker
      plectin.
AB  - Chemokine-induced polarization of lymphocytes involves the rapid collapse of
      vimentin intermediate filaments (IFs) into an aggregate within the uropod. Little
      is known about the interactions of lymphocyte vimentin with other cytoskeletal
      elements. We demonstrate that human peripheral blood T lymphocytes express
      plectin, an IF-binding, cytoskeletal cross-linking protein. Plectin associates
      with a complex of structural proteins including vimentin, actin, fodrin, moesin,
      and lamin B in resting peripheral blood T lymphocytes. During chemokine-induced
      polarization, plectin redistributes to the uropod associated with vimentin and
      fodrin; their spatial distribution indicates that this vimentin-plectin-fodrin
      complex provides a continuous linkage from the nucleus (lamin B) to the cortical
      cytoskeleton. Overexpression of the plectin IF-binding domain in the T cell line
      Jurkat induces the perinuclear aggregation of vimentin IFs. Plectin is therefore
      likely to serve as an important organizer of the lymphocyte cytoskeleton and may
      regulate changes of lymphocyte cytoarchitecture during polarization and
      extravasation.

PMID- 11441067
TI  - Chromatin-independent binding of serum amyloid P component to apoptotic cells.
AB  - Human serum amyloid P component (SAP) is a glycoprotein structurally belonging to
      the pentraxin family of proteins, which has a characteristic pentameric
      organization. Mice with a targeted deletion of the SAP gene develop antinuclear
      Abs, which was interpreted as evidence for a role of SAP in controlling the
      degradation of chromatin. However, in vitro SAP also can bind to
      phosphatidylethanolamine, a phospholipid which in normal cells is located mainly
      in the inner leaflet of the cell membrane, to be translocated to the outer
      leaflet of the cell membrane during a membrane flip-flop. We hypothesized that
      SAP, because of its specificity for phosphatidylethanolamine, may bind to
      apoptotic cells independent of its nuclear binding. Calcium-dependent binding of
      SAP to early, nonpermeable apoptotic Jurkat, SKW, and Raji cells was indeed
      observed. Experiments with flip-flopped erythrocytes confirmed that SAP bound to
      early apoptotic cells via exposed phosphatidylethanolamine. Binding of SAP was
      stronger to late, permeable apoptotic cells. Experiments with enucleated
      neutrophils, with DNase/RNase treatment of late apoptotic Jurkat cells, and
      competition experiments with histones suggested that binding of SAP to late
      apoptotic cells was largely independent of chromatin. Confocal laser microscopic
      studies indeed suggested that SAP bound to these apoptotic cells mainly via the
      blebs. Thus, this study shows that SAP binds to apoptotic cells already at an
      early stage, which raises the possibility that SAP is involved in dealing with
      apoptotic cells in vivo.

PMID- 11441068
TI  - Expansion of the antigenic repertoire of a single T cell receptor upon T cell
      activation.
AB  - Activated T cells and their naive precursors display different functional
      avidities for peptide/MHC, but are thought to have identical antigenic
      repertoires. We show that, following activation with a cognate mimotope (NRP),
      diabetogenic CD8(+) T cells expressing a single TCR (8.3) respond vigorously to
      numerous peptide analogs of NRP that were unable to elicit any responses from
      naive 8.3-CD8(+) T cells, even at high concentrations. The NRP-reactive, in vivo
      activated CD8(+) cells arising in pancreatic islets of nonobese diabetic mice are
      similarly promiscuous for peptide/MHC, and paradoxically this promiscuity expands
      as the aviditiy of the T cell population for NRP/MHC increases with age. Thus,
      activation and avidity maturation of T lymphocyte populations can lead to
      dramatic expansions in the range of peptides that elicit functional T cell
      responses.

PMID- 11441069
TI  - Antigen presentation by liver cells controls intrahepatic T cell trapping,
      whereas bone marrow-derived cells preferentially promote intrahepatic T cell
      apoptosis.
AB  - Systemic activation and proliferation of CD8(+) T cells result in T cell
      accumulation in the liver, associated with T cell apoptosis and liver injury.
      However, the role of Ag and APC in such accumulation is not clear. Bone marrow
      chimeras were constructed to allow Ag presentation in all tissues or
      alternatively to restrict presentation to either bone marrow-derived or non-bone
      marrow-derived cells. OVA-specific CD8(+) T cells were introduced by adoptive
      transfer and then activated using peptide, which resulted in clonal expansion
      followed by deletion. Ag presentation by liver non-bone marrow-derived cells was
      responsible for most of the accumulation of activated CD8(+) T cells. In
      contrast, Ag presentation by bone marrow-derived cells resulted in less
      accumulation of T cells in the liver, but a higher frequency of apoptotic cells
      within the intrahepatic T cell population. In unmodified TCR-transgenic mice, Ag
      induced T cell deletion and intrahepatic accumulation of CD8(+) T cells result in
      hepatocyte damage, with the release of aminotransaminases. Our experiments show
      that such liver injury may occur in the absence of Ag presentation by the
      hepatocytes themselves, arguing for an indirect mechanism of liver damage.

PMID- 11441070
TI  - Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte
      cytotoxicity.
AB  - Previous work showed that neurons of the CNS are protected against perforin
      mediated T cell cytotoxicity, but are susceptible to Fas-mediated apoptosis. In
      this study, we report that Fas ligand (FasL) expression by neurons is involved in
      protection against perforin-mediated T cell cytotoxicity. Gene transcripts for
      FasL were identified in single murine hippocampal neurons by RT-PCR combined with
      patch clamp electrophysiology, and constitutive expression of FasL protein was
      confirmed in neurons by immunohistochemistry. Neurons derived from wild-type
      C57BL/6 (BL6) mice and mutant BL6.gld mice lacking functional FasL were
      confronted with allogeneic CTLs and continuously monitored in real time for
      changes in levels of intracellular calcium ([Ca(2+)](i)), an indicator of
      cytotoxic damage. Perforin-mediated plasma membrane lysis, characterized by
      rapid, massive [Ca(2+)](i) influx into the target cells within 0.5 h, was not
      detected in wild-type neurons. In striking contrast, FasL-deficient neurons
      showed rapid increase in [Ca(2+)](i) within 0.5 h, reflecting perforin-dependent
      cell lysis. FasL seems to protect neurons by blocking degranulation of CTLs,
      since CD3-induced release of cytotoxic granules was reduced by coapplication of
      Fas-specific Abs or rFasL.

PMID- 11441071
TI  - The Peyer's patch microenvironment suppresses T cell responses to chemokines and
      other stimuli.
AB  - Immunosurveillance of mucosal sites presents immune cells with challenges not
      encountered in the periphery. T cells in the gut must distinguish enteric
      pathogens from innocuous non-self Ag derived from food or commensal bacteria. The
      mechanisms that regulate T cells in the gut remain incompletely understood. We
      assessed the effect of the Peyer's patch microenvironment on T cell responses to
      chemokines. Chemokines are believed to play an important role during T cell
      priming by facilitating T cell migration into and within lymphoid tissues as well
      as T cell encounter and interaction with APCs. We found a profound suppression of
      chemokine-stimulated T cell chemotaxis and actin polymerization in Peyer's patch
      relative to lymph node. Chemokine hyporesponsiveness is imposed upon T cells
      within hours of their entry into Peyer's patches and is reversed following their
      removal. Suppression was not restricted to chemokine stimulation, as T cell
      responses to Con A and PMA were also suppressed. The global nature of this defect
      is further underscored by an impairment in calcium mobilization. Evidence
      indicates that a soluble factor contributes to this hyporesponsiveness, and
      comparison of Peyer's patches and lymph nodes revealed striking differences in
      their chemokine and cytokine constitution, indicating a marked Th2 bias in the
      Peyer's patches. The role of the Th2 microenvironment in mediating suppression is
      suggested by the ability of Nippostrongylus brasiliensis to elicit
      hyporesponsiveness in lymph node T cells. The suppressive milieu encountered by T
      cells in Peyer's patches may be critical for discouraging undesired immune
      responses and promoting tolerance.

PMID- 11441072
TI  - A genetic model of stress displays decreased lymphocytes and impaired antibody
      responses without altered susceptibility to Streptococcus pneumoniae.
AB  - Stress pathways affect immune function, the most notable of these pathways being
      activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although HPA
      activation has generally been relegated to an immunosuppressive role, recent
      evidence suggests that stress and HPA activation can be immunoenhancing in
      certain situations. To investigate specific effects of stress on immune function,
      we used a genetic model of chronic stress wherein transgenic mice overexpress
      corticotropin-releasing hormone (CRH), a primary mediator of the stress response.
      In these mice, CRH is overproduced in the brain, leading to chronic activation of
      the HPA axis. We found that CRH-transgenic mice have decreased leukocyte numbers
      in lymphoid compartments, with preferential loss of B lymphocytes. They also
      exhibit decreased Ab production and impaired isotype switching in response to
      immunization with a thymus-dependent Ag, phosphocholine-keyhole limpet
      hemocyanin. Despite these deficits, immunization protected CRH-transgenic and
      wild-type mice equally well against lethal challenge with Streptococcus
      pneumoniae, an encapsulated Gram-positive bacterium known to require Ab-mediated
      opsonization for clearance. While IgG responses are severely depressed in these
      mice, IgM titers are only modestly decreased. This fairly robust IgM response may
      be sufficient to protect against S. pneumoniae. Additionally, while total
      leukocyte numbers are decreased in these mice, neutrophil numbers are increased.
      This increase in number of neutrophils may compensate for the depressed IgG
      response, allowing adequate host defense during chronic stress.

PMID- 11441073
TI  - Competitive inhibition in vivo and skewing of the T cell repertoire of antigen
      specific CTL priming by an anti-peptide-MHC monoclonal antibody.
AB  - We have recently described a mAb, KP15, directed against the MHC-I/peptide
      molecular complex consisting of H-2D(d) and a decamer peptide corresponding to
      residues 311-320 of the HIV IIIB envelope glycoprotein gp160. When administered
      at the time of primary immunization with a vaccinia virus vector encoding gp160,
      the mAb blocks the subsequent appearance of CD8(+) CTL with specificity for the
      immunodominant Ag, P18-I10, presented by H-2D(d). This inhibition is specific for
      this particular peptide Ag; another H-2D(d)-restricted gp160 encoded epitope from
      a different HIV strain is not affected, and an H-2L(d)-restricted epitope encoded
      by the viral vector is also not affected. Using functional assays and specific
      immunofluorescent staining with multivalent, labeled H-2D(d)/P18-I10 complexes
      (tetramers), we have enumerated the effects of blocking of priming on the
      subsequent appearance, avidity, and TCR Vbeta usage of Ag-specific CTL. Ab
      blocking skews the proportion of high avidity cells emerging from immunization.
      Surprisingly, Vbeta7-bearing Ag-specific TCR are predominantly inhibited, while
      TCR of several other families studied are not affected. The ability of a specific
      MHC/peptide mAb to inhibit and divert the CD8(+) T cell response holds
      implications for vaccine design and approaches to modulate the immune response in
      autoimmunity.

PMID- 11441074
TI  - IL-6 inhibits the tolerogenic function of CD8 alpha+ dendritic cells expressing
      indoleamine 2,3-dioxygenase.
AB  - The outcome of dendritic cell (DC) presentation of tumor and/or self peptides,
      including P815AB (a tumor peptide of murine mastocytoma cells) and NRP-A7 (a
      synthetic peptide mimotope recognized by diabetogenic T cells), may depend on a
      balance between the activities of immunogenic (CD8alpha(-)) and tolerogenic
      (CD8alpha(+)) DC. By virtue of their respective actions on CD8(-) and CD8(+) DC,
      IL-12 and IFN-gamma have functionally opposing effects on peptide presentation by
      the CD8(-) DC subset, and IFN-gamma-activated CD8(+) DC mediate tolerogenic
      effects that prevail over the adjuvant activity of IL-12 on CD8(-) DC. We have
      previously shown that CD40 ligation abrogates the tolerogenic potential of CD8(+)
      DC, an effect associated with an impaired capacity of the CD40-modulated and IFN
      gamma-treated DC to degrade tryptophan and initiate T cell apoptosis in vitro. We
      report here that IL-6 may both replace (upon administration of the recombinant
      cytokine) and mediate (as assessed by the use of neutralizing Abs) the effect of
      CD40 ligation in ablating the tolerogenic activity of CD8(+) DC. The activity of
      IL-6 includes down-regulation of IFN-gammaR expression in the CD8(+) DC subset
      and correlates to a reduced ability of these cells to metabolize tryptophan and
      initiate T cell apoptosis in vitro.

PMID- 11441075
TI  - Enforced expression of GATA-3 during T cell development inhibits maturation of
      CD8 single-positive cells and induces thymic lymphoma in transgenic mice.
AB  - The zinc finger transcription factor GATA-3 is of critical importance for early T
      cell development and commitment of Th2 cells. To study the role of GATA-3 in
      early T cell development, we analyzed and modified GATA-3 expression in vivo. In
      mice carrying a targeted insertion of a lacZ reporter on one allele, we found
      that GATA-3 transcription in CD4(+)CD8(+) double-positive thymocytes correlated
      with the onset of positive selection events, i.e., TCRalphabeta up-regulation and
      CD69 expression. LacZ expression remained high ( approximately 80% of cells)
      during maturation of CD4 single-positive (SP) cells in the thymus, but in
      developing CD8 SP cells the fraction of lacZ-expressing cells decreased to <20%.
      We modified this pattern by enforced GATA-3 expression driven by the CD2 locus
      control region, which provides transcription of GATA-3 throughout T cell
      development. In two independent CD2-GATA3-transgenic lines, approximately 50% of
      the mice developed thymic lymphoblastoid tumors that were CD4(+)CD8(+/low) and
      mostly CD3(+). In tumor-free CD2-GATA3-transgenic mice, the total numbers of CD8
      SP cells in the thymus were within normal ranges, but their maturation was
      hampered, as indicated by increased apoptosis of CD8 SP cells and a selective
      deficiency of mature CD69(low)HSA(low) CD8 SP cells. In the spleen and lymph
      nodes, the numbers of CD8(+) T cells were significantly reduced. These findings
      indicate that GATA-3 supports development of the CD4 lineage and inhibits
      maturation of CD8 SP cells in the thymus.

PMID- 11441076
TI  - Enforced expression of GATA-3 in transgenic mice inhibits Th1 differentiation and
      induces the formation of a T1/ST2-expressing Th2-committed T cell compartment in
      vivo.
AB  - The transcription factor GATA-3 is essential for early T cell development and
      differentiation of naive CD4(+) T cells into Th2 effector cells. To study the
      function of GATA-3 during T cell-mediated immune responses in vivo, we
      investigated CD2-GATA3-transgenic mice in which GATA-3 expression is driven by
      the CD2 locus control region. Both in the CD4(+) and the CD8(+) T cell population
      the proportion of cells exhibiting a CD44(high)CD45RB(low)CD62L(low) Ag
      experienced phenotype was increased. In CD2-GATA3-transgenic mice, large
      fractions of peripheral CD4(+) T cells expressed the IL-1 receptor family member
      T1/ST2, indicative of advanced Th2 commitment. Upon in vitro T cell stimulation,
      the ability to produce IL-2 and IFN-gamma was decreased. Moreover, CD4(+) T cells
      manifested rapid secretion of the Th2 cytokines IL-4, IL-5, and IL-10,
      reminiscent of Th2 memory cells. In contrast to wild-type CD4(+) cells, which
      lost GATA-3 expression when cultured under Th1-polarizing conditions, CD2-GATA3
      transgenic CD4(+) cells maintained expression of GATA-3 protein. Under Th1
      conditions, cellular proliferation of CD2-GATA3-transgenic CD4(+) cells was
      severely hampered, IFN-gamma production was decreased and Th2 cytokine production
      was increased. Enforced GATA-3 expression inhibited Th1-mediated in vivo
      responses, such as Ag-specific IgG2a production or a delayed-type
      hypersensitivity response to keyhole limpet hemocyanin. Collectively, these
      observations indicate that enforced GATA-3 expression selectively inhibits Th1
      differentiation and induces Th2 differentiation. The increased functional
      capacity to secrete Th2 cytokines, along with the increased expression of surface
      markers for Ag-experienced Th2-committed cells, would argue for a role of GATA-3
      in Th2 memory formation.

PMID- 11441077
TI  - B cell receptor cross-linking triggers a caspase-8-dependent apoptotic pathway
      that is independent of the death effector domain of Fas-associated death domain
      protein.
AB  - We have previously reported that B cell receptors, depending on the degree to
      which they are cross-linked, can promote apoptosis in various human B cell types.
      In this study, we show that B cell receptors can trigger two apoptotic pathways
      according to cross-linking and that these pathways control mitochondrial
      activation in human Burkitt's lymphoma cells. Whereas soluble anti-mu Ab triggers
      caspase-independent mitochondrial activation, cross-linked anti-mu Ab induces an
      apoptotic response associated with a caspase-dependent loss of mitochondrial
      transmembrane potential. This B cell receptor-mediated caspase-dependent
      mitochondrial activation is associated with caspase-8 activation. We show here
      that caspase-8 inhibitors strongly decrease cross-linking-dependent B cell
      receptor-mediated apoptosis in Burkitt's lymphoma BL41 cells. These inhibitors
      act upstream from the mitochondria as they prevented the loss of mitochondrial
      membrane potential observed in B cell receptor-treated BL41 cells. Caspase-8
      activation in these cells was also evident from the detection of cleaved
      fragments of caspase-8 and the cleavage of specific substrates, including Bid.
      Our data show that cross-linked B cell receptors induced an apoptotic pathway
      involving sequential caspase-8 activation, loss of mitochondrial membrane
      potential, and the activation of caspase-9 and caspase-3. Cells expressing a
      dominant negative mutant of Fas-associated death domain protein were sensitive to
      cross-linked B cell receptor-induced caspase-8 activation and apoptosis;
      therefore, this caspase-8 activation was independent of the death effector domain
      of Fas-associated death domain protein.

PMID- 11441078
TI  - The dendritic cell populations of mouse lymph nodes.
AB  - The dendritic cells (DC) of mouse lymph nodes (LN) were isolated, analyzed for
      surface markers, and compared with those of spleen. Low to moderate staining of
      LN DC for CD4 and low staining for CD8 was shown to be attributable to pickup of
      these markers from T cells. Excluding this artifact, five LN DC subsets could be
      delineated. They included the three populations found in spleen (CD4(+)8(-)DEC
      205(-), CD4(-)8(-)DEC-205(-), CD4(-)8(+)DEC-205(+)), although the CD4-expressing
      DC were of low incidence. LN DC included two additional populations,
      characterized by relatively low expression of CD8 but moderate or high expression
      of DEC-205. Both appeared among the DC migrating out of skin into LN, but only
      one was restricted to skin-draining LN and was identified as the mature form of
      epidermal Langerhans cells (LC). The putative LC-derived DC displayed the
      following properties: large size; high levels of class II MHC, which persisted to
      some extent even in CIITA null mice; expression of very high levels of DEC-205
      and of CD40; expression of many myeloid surface markers; and no expression of CD4
      and only low to moderate expression of CD8. The putative LC-derived DC among skin
      emigrants and in LN also showed strong intracellular staining of langerin.

PMID- 11441079
TI  - IL-12 decreases activation-induced cell death in human naive Th cells
      costimulated by intercellular adhesion molecule-1. I. IL-12 alters caspase
      processing and inhibits enzyme function.
AB  - Th cells can receive costimulatory signals through the LFA-1/ICAM-1 accessory
      pathway that are sufficient to induce early Th cell proliferation, but not
      subsequent cell expansion and maintenance of cell viability. To investigate the
      regulatory role for IL-12 in ICAM-1-mediated costimulation, human naive Th cells
      were stimulated with coimmobilized anti-CD3 mAb and ICAM-1 Ig in the presence or
      absence of IL-12. The ICAM-1-mediated costimulatory signals in this model
      resulted in early Th cell proliferation followed by cell death that was partially
      mediated by Fas and involved loss of mitochondrial membrane potential, processing
      of procaspase-9 and -3, and activation of caspase-3. Addition of IL-12 prevented
      activation-induced cell death and promoted late proliferation. ICAM-1 + IL-12
      costimulated Th cells were resistant to Fas-mediated cell death through a
      mechanism that did not appear to involve a decrease in either Fas or Fas ligand
      expression. IL-12 did not inhibit the loss of mitochondrial membrane potential
      induced by ICAM-1-mediated costimulation, and this finding was consistent with
      the inability of IL-12 to increase expression of the antiapoptotic Bcl-2 family
      members, Bcl-2 and Bcl-x(L). Interestingly, IL-12 promoted an altered processing
      of procaspase-9 and -3 and a decrease in the percentage of cells displaying
      caspase-3 catalytic function. In conclusion, we now describe a novel regulatory
      function for IL-12 in preventing Th cell death and, as a result, in greatly
      increasing Th cell viability and expansion. Together, our findings indicate that
      IL-12 may perform this regulatory role by preventing Fas-mediated activation
      induced cell death through inhibition of caspase-3 enzyme activity.

PMID- 11441080
TI  - The binding of thymus leukemia (TL) antigen tetramers to normal intestinal
      intraepithelial lymphocytes and thymocytes.
AB  - Thymus leukemia (TL) Ags belong to the family of nonclassical MHC class I Ags and
      can be recognized by both TCRalphabeta and TCRgammadelta CTL with TL, but not H-2
      restriction. We previously reported that the CTL epitope is TAP independent, but
      the antigenic molecule(s) presented by TL has yet to be determined. In the
      present study, TL tetramers were prepared with T3(b)-TL and murine beta(2)
      microglobulin, not including antigenic peptides, and binding specificity was
      studied. CTL clones against TL Ags were stained with the T3(b)-TL tetramer, and
      the binding shown to be CD3 and CD8 dependent. Normal lymphocytes from various
      origins were also studied. Surprisingly, most CD8(+) intraepithelial lymphocytes
      derived from the small intestines (iIEL), as well as CD8(+) and CD4(+)CD8(+)
      thymocytes, were stained, while only very minor populations of CD8(+) cells
      derived from other peripheral lymphoid tissues, such as spleen and lymph nodes,
      were positive. The binding of T3(b)-TL tetramers to CD8(+) iIEL and thymocytes
      was CD8 dependent, but CD3 independent, in contrast to that to TL-restricted CTL.
      These results altogether showed that TL-restricted CTL can be monitored by CD3
      dependent binding of T3(b)-TL tetramers. In addition, CD3-independent T3(b)-TL
      tetramer binding to iIEL and thymocytes may imply that TL expressed on intestinal
      epithelium and cortical thymocytes has a physiological function interacting with
      these tetramer(+)CD8(+) T lymphocytes.

PMID- 11441081
TI  - Wnt signaling regulates hemopoiesis through stromal cells.
AB  - Hemopoietic cells develop in a complex milieu that is made up of diverse
      components, including stromal cells. Wnt genes, which are known to regulate the
      fate of the cells in a variety of tissues, are expressed in hemopoietic organs.
      However, their roles in hemopoiesis are not well characterized. In this study, we
      examined the roles of Wnt proteins in hemopoiesis using conditioned medium
      containing Wnt-3a. This conditioned medium dramatically reduced the production of
      B lineage cells and myeloid lineage cells, except for macrophages in the long
      term bone marrow cultures grown on stromal cells, although the sensitivity to the
      conditioned medium differed, depending on the hemopoietic lineage. In contrast,
      the same conditioned medium did not affect the generation of B lineage or myeloid
      lineage cells in stromal cell-free conditions. These results suggested that Wnt
      proteins exert their effects through stromal cells. Indeed, these effects were
      mimicked by the expression of a stabilized form of beta-catenin in stromal cells.
      In this study, we demonstrated that Wnt signaling regulates hemopoiesis through
      stromal cells with selectivity and different degrees of the effect, depending on
      the hemopoietic lineage in the hemopoietic microenvironment.

PMID- 11441082
TI  - Regulation of TGF-beta response during T cell activation is modulated by IL-10.
AB  - TGF-beta1 is an important pleiotropic cytokine that has been described to have
      both stimulatory and inhibitory effects on cell growth and differentiation. For
      several cell types, the effect of TGF-beta1 was found to correlate with the
      differentiation stage of the cells and the presence of other cytokines. In this
      report, we address the influence of TGF-beta1 on CD4(+) T cell activation by
      evaluating the effect of TGF-beta1 on the proliferative and cytokine responses of
      purified resting and activated human or mouse CD4(+) T cells. TGF-beta1 inhibits
      proliferation and cytokine secretion on resting CD4(+) T cells but has no
      inhibitory effect on activated T cells. Moreover, TGF-beta1 unresponsiveness of
      activated T cells was correlated with a down-regulation in the expression of the
      TGF-beta receptor type II. Interestingly, IL-10 addition enhances TGF-beta
      receptor type II expression and restores TGF-beta responsiveness on activated T
      cells. These results indicated that TGF-beta responsiveness is sequentially
      regulated on T cells by the modulation of the of TGF-beta receptor type II chain
      expression. Moreover, we have identified a novel regulatory role of IL-10 on TGF
      beta-dependent T cell growth that can explain the control of T cell activation on
      chronic vs acute inflammatory sites.

PMID- 11441083
TI  - A role for IL-12 receptor expression and signal transduction in host defense in
      leprosy.
AB  - The generation of cell-mediated immunity against intracellular infection involves
      the production of IL-12, a critical cytokine required for the development of Th1
      responses. The biologic activities of IL-12 are mediated through a specific, high
      affinity IL-12R composed of an IL-12Rbeta1/IL-12Rbeta2 heterodimer, with the IL
      12Rbeta2 chain involved in signaling via Stat4. We investigated IL-12R expression
      and function in human infectious disease, using the clinical/immunologic spectrum
      of leprosy as a model. T cells from tuberculoid patients, the resistant form of
      leprosy, are responsive to IL-12; however, T cells from lepromatous patients, the
      susceptible form of leprosy, do not respond to IL-12. We found that the IL
      12Rbeta2 was more highly expressed in tuberculoid lesions compared with
      lepromatous lesions. In contrast, IL-12Rbeta1 expression was similar in both
      tuberculoid and lepromatous lesions. The expression of IL-12Rbeta2 on T cells was
      up-regulated by Mycobacterium leprae in tuberculoid but not in lepromatous
      patients. Furthermore, IL-12 induced Stat4 phosphorylation and DNA binding in M.
      leprae-activated T cells from tuberculoid but not from lepromatous patients.
      Interestingly, IL-12Rbeta2 in lepromatous patients could be up-regulated by
      stimulation with M. tuberculosis. These data suggest that Th response to M.
      leprae determines IL-12Rbeta2 expression and function in host defense in leprosy.

PMID- 11441084
TI  - Identification of new epitopes from four different tumor-associated antigens:
      recognition of naturally processed epitopes correlates with HLA-A*0201-binding
      affinity.
AB  - Forty-two wild-type and analogue peptides derived from p53, carcinoembryonic Ag,
      Her2/neu, and MAGE2/3 were screened for their capacity to induce CTLs, in vitro,
      capable of recognizing tumor target lines. All the peptides bound HLA-A*0201 and
      two or more additional A2 supertype alleles with an IC(50) of 500 nM or less. A
      total of 20 of 22 wild-type and 9 of 12 single amino acid substitution analogues
      were found to be immunogenic in primary in vitro CTL induction assays, using
      normal PBMCs and GM-CSF/IL-4-induced dendritic cells. These results suggest that
      peripheral T cell tolerance does not prevent, in this system, induction of CTL
      responses against tumor-associated Ag peptides, and confirm that an HLA class I
      affinity of 500 nM or less is associated with CTL epitope immunogenicity. CTLs
      generated by 13 of 20 of the wild-type epitopes, 6 of 9 of the single, and 2 of 5
      of the double substitution analogues tested recognized epitopes generated by
      endogenous processing of tumor-associated Ags and expressed by HLA-matched cancer
      cell lines. Further analysis revealed that recognition of naturally processed Ag
      was correlated with high HLA-A2.1-binding affinity (IC(50) = 200 nM or less; p =
      0.008), suggesting that high binding affinity epitopes are frequently generated
      and can be recognized as a result of natural Ag processing. These results have
      implications for the development of cancer vaccines, in particular, and for the
      process of epitope selection in general.

PMID- 11441085
TI  - Engagement of Fc epsilon RI on human monocytes induces the production of IL-10
      and prevents their differentiation in dendritic cells.
AB  - The local cytokine environment and the presence of stimulatory signals determine
      whether circulating monocytes will finally acquire characteristics of dendritic
      cells (DCs) or macrophages. Because FcepsilonRI expressed on professional APCs,
      e.g., monocytes and DCs, has been suggested to play a key role in the
      pathophysiology of atopic diseases, we evaluated the effect of receptor ligation
      on the generation of monocyte-derived DCs (MoDCs). Aggregation of FcepsilonRI at
      the initiation of the IL-4-GM-CSF-driven differentiation resulted in the
      emergence of macrophage-like cells with a strong expression of the mannose
      receptor and a low level of CD1a and the DC-specific markers CD83 and the actin
      bundling protein (p55). These cells sustained the ability to take up FITC-labeled
      Escherichia coli by phagocytosis and were significantly less efficient in
      stimulating purified allogeneic T cells. In addition, receptor ligation of
      FcepsilonRI at the beginning of the culture prevented the generation of MoDCs,
      mainly due to a dramatic increase in the IL-10 production. These results suggest
      that FcepsilonRI aggregation prevents the generation of CD1a(+) MoDCs and imply a
      novel pivotal function of this receptor in modulating the differentiation of
      monocytes.

PMID- 11441086
TI  - Peripheral T cells become sensitive to glucocorticoid- and stress-induced
      apoptosis in transgenic mice overexpressing SRG3.
AB  - Immature double-positive thymocytes are sensitive to glucocorticoid (GC)-induced
      apoptosis, whereas mature single-positive T cells are relatively resistant.
      Thymocytes seem to acquire resistance to GCs during differentiation into mature
      single-positive thymocytes. However, detailed knowledge concerning what
      determines the sensitivity of thymocytes to GCs and how GC sensitivity is
      regulated in thymocytes during development is lacking. We have previously
      reported that the murine SRG3 gene (for SWI3-related gene) is required for GC
      induced apoptosis in a thymoma cell line. Herein, we provide results suggesting
      that the expression level of SRG3 protein determines the GC sensitivity of T
      cells in mice. SRG3 associates with the GC receptor in the thymus, but rarely in
      the periphery. Transgenic overexpression of the SRG3 protein in peripheral T
      cells induces the formation of the complex and renders the cells sensitive to GC
      induced apoptosis. Our results also show that blocking the formation of the SRG3
      GC receptor complex with a dominant negative mutant form of SRG3 decreases GC
      sensitivity in thymoma cells. In addition, mice overexpressing the SRG3 protein
      appear to be much more susceptible to stress-induced deletion of peripheral T
      cells than normal mice, which may result in an immunosuppressive state in an
      animal.

PMID- 11441087
TI  - A pivotal role for DNase I-sensitive regions 3b and/or 4 in the induction of
      somatic hypermutation of IgH genes.
AB  - Chimeric mice were prepared from embryonic stem cells transfected with IgH genes
      as transgenes and RAG-2-deficient blastocysts for the purpose of identifying the
      cis-acting elements responsible for the induction of somatic hypermutation. Among
      the three transgene constructs used, the V(H) promoter, the rearranged V(H)-D
      J(H), an intron enhancer/matrix attachment region, and human Cmu were common to
      all, but the 3'-untranslated region in each construct was different. After
      immunization of mice with a T cell-dependent Ag, the distribution and frequency
      of hypermutation in transgenes were analyzed. The transgene lacking the 3'
      untranslated region showed a marginal degree of hypermutation. Addition of the 3'
      enhancer resulted in a slight increase in the number of mutations. However, the
      transgene containing DNase I-sensitive regions 3b and 4 in addition to the 3'
      enhancer showed more than a 10-fold increase in hypermutation, reaching levels
      comparable to those observed in endogenous V(H)186.2 genes of C57BL/6 mice.

PMID- 11441088
TI  - Monomeric class I molecules mediate TCR/CD3 epsilon/CD8 interaction on the
      surface of T cells.
AB  - Both CD8 and the TCR bind to MHC class I molecules during physiologic T cell
      activation. It has been shown that for optimal T cell activation to occur, CD8
      must be able to bind the same class I molecule that is bound by the TCR. However,
      no direct evidence for the class I-dependent association of CD8 and the TCR has
      been demonstrated. Using fluorescence resonance energy transfer, we show directly
      that a single class I molecule causes TCR/CD8 interaction by serving as a docking
      molecule for both CD8 and the TCR. Furthermore, we show that CD3epsilon is
      brought into close proximity with CD8 upon TCR/CD8 association. These
      interactions are not dependent on the phosphorylation events characteristic of T
      cell activation. Thus, MHC class I molecules, by binding to both CD8 and the TCR,
      mediate the reorganization of T cell membrane components to promote cellular
      activation.

PMID- 11441089
TI  - CD28 signaling augments Elk-1-dependent transcription at the c-fos gene during
      antigen stimulation.
AB  - Untransformed CD4(+) Th1 cells stimulated with Ag and APC demonstrated a
      dependence on B7- and CD28-mediated costimulatory signals for the expression and
      function of AP-1 proteins. The induction of transactivation by the c-fos gene
      regulator Elk-1 mirrored this requirement for TCR and CD28 signal integration. c
      Jun N-terminal kinase (JNK) (but not extracellular signal-regulated kinase or
      p38) protein kinase activity was similarly inhibited by neutralizing anti-B7
      mAbs. Blockade of JNK protein kinase activity with SB 202190 prevented both Elk-1
      transactivation and c-Fos induction. These results identify a unique role for B7
      costimulatory molecules and CD28 in the activation of JNK during Ag stimulation
      in Th1 cells, and suggest that JNK regulates Elk-1 transactivation at the c-fos
      gene to promote the formation of AP-1 complexes important to IL-2 gene
      expression.

PMID- 11441090
TI  - Functional evidence that conserved TCR CDR alpha 3 loop docking governs the cross
      recognition of closely related peptide:class I complexes.
AB  - The TCR recognizes its peptide:MHC (pMHC) ligand by assuming a diagonal
      orientation relative to the MHC helices, but it is unclear whether and to what
      degree individual TCRs exhibit docking variations when contacting similar pMHC
      complexes. We analyzed monospecific and cross-reactive recognition by diverse
      TCRs of an immunodominant HVH-1 glycoprotein B epitope (HSV-8p) bound to two
      closely related MHC class I molecules, H-2K(b) and H-2K(bm8). Previous studies
      indicated that the pMHC portion likely to vary in conformation between the two
      complexes resided at the N-terminal part of the complex, adjacent to peptide
      residues 2-4 and the neighboring MHC side chains. We found that CTL clones
      sharing TCR beta-chains exhibited disparate recognition patterns, whereas those
      with drastically different TCRbeta-chains but sharing identical TCRalpha CDR3
      loops displayed identical functional specificity. This suggested that the
      CDRalpha3 loop determines the TCR specificity in our model, the conclusion
      supported by modeling of the TCR over the actual HSV-8:K(b) crystal structure.
      Importantly, these results indicate a remarkable conservation in CDRalpha3
      positioning, and, therefore, in docking of diverse TCRalphabeta heterodimers onto
      variant peptide:class I complexes, implying a high degree of determinism in
      thymic selection and T cell activation.

PMID- 11441091
TI  - Signal transduction by human-restricted Fc gamma RIIa involves three distinct
      cytoplasmic kinase families leading to phagocytosis.
AB  - Recent experiments indicate an important role for Src family and Syk protein
      tyrosine kinases and phosphatidylinositol 3-kinase in the signal transduction
      process initiated by mouse receptors for IgG and leading to phagocytosis.
      Considerably less is known regarding signal transduction by the human-restricted
      IgG receptor, FcgammaRIIa. Furthermore, the relationship among the Src family,
      Syk, and phosphatidylinositol 3-kinase in phagocytosis is not understood. Here,
      we show that FcgammaRIIa is phosphorylated by an Src family member, which results
      in recruitment and concomitant activation of the distal enzymes Syk and
      phosphatidylinositol 3-kinase. Using a FcgammaRI-p85 receptor chimera
      cotransfected with kinase-inactive mutants of Syk or application of a
      pharmacological inhibitor of Syk, we show that Syk acts in parallel with
      phosphatidylinositol 3-kinase. Our results indicate that FcgammaRIIa-initiated
      monocyte or neutrophil phagocytosis proceeds from the clustered IgG receptor to
      Src to phosphatidylinositol 3-kinase and Syk.

PMID- 11441092
TI  - Unexpected characteristics of the IFN-gamma reporters in nontransformed T cells.
AB  - Analysis of the IFN-gamma promoter has primarily been conducted by transient
      expression of reporter constructs in transformed cells. However, the activity of
      cis elements may differ when expressed transiently compared with their activity
      within native chromatin. Furthermore, the transcription factors and signaling
      mechanisms in transformed cells may differ from those in normal T cells. To
      analyze IFN-gamma promoter regulation in normal T cells, we developed a novel
      retroviral bottom-strand reporter system to allow the chromatin integration of
      promoter regions in primary developing T cells. As controls, both the IL-2 and IL
      4 promoters were inducible in this system, with the IL-4 reporter having Th2
      specific activity. Strikingly, the IFN-gamma promoter exhibited constitutive
      activity in both Th1 and Th2 subsets, in contrast to the behavior of the
      endogenous IFN-gamma gene, which is inducible only in Th1 cells. In mapping this
      activity, we found that the AP-1/GM-CSF site in the distal promoter element is
      the most critical element for the constitutive activity. Transgenic reporter
      lines for the IFN-gamma promoter confirmed the constitutive behavior of the
      isolated IFN-gamma promoter. This constitutive activity was resistant to
      inhibition by cyclosporin A and was independent of Stat4 and p38 mitogen
      activated protein kinase. These results suggest that IFN-gamma promoter
      regulation may require cis elements residing either downstream or >3.4 kb
      upstream of the transcriptional start site, involving repression of constitutive
      activity.

PMID- 11441093
TI  - Chromatin remodeling at the Ig loci prior to V(D)J recombination.
AB  - Rearrangement of Ig H and L chain genes is highly regulated and takes place
      sequentially during B cell development. Several lines of evidence indicate that
      chromatin may modulate accessibility of the Ig loci for V(D)J recombination. In
      this study, we show that remodeling of V and J segment chromatin occurs before
      V(D)J recombination at the endogenous H and kappa L chain loci. In recombination
      activating gene-deficient pro-B cells, there is a reorganization of nucleosomal
      structure over the H chain J(H) cluster and increased DNase I sensitivity of V(H)
      and J(H) segments. The pro-B/pre-B cell transition is marked by a decrease in the
      DNase I sensitivity of V(H) segments and a reciprocal increase in the nuclease
      sensitivity of Vkappa and Jkappa segments. In contrast, J(H) segments remain
      DNase I sensitive, and their nucleosomal organization is maintained in mu(+)
      recombination-activating gene-deficient pre-B cells. These results indicate that
      initiation of rearrangement is associated with changes in the chromatin structure
      of both V and J segments, whereas stopping recombination involves changes in only
      V segment chromatin. We further find an increase in histone H4 acetylation at
      both the H and kappa L chain loci at the pro-B cell stage. Although histone H4
      acetylation appears to be an early change associated with B cell commitment,
      acetylation alone is not sufficient to promote subsequent modifications in Ig
      chromatin.

PMID- 11441094
TI  - Functional CD4 T cells after intercellular molecular transfer of 0X40 ligand.
AB  - OX40/OX40 ligand (OX40L) proteins play critical roles in the T cell-B cell and T
      cell-dendritic cell interactions. Here we describe the intercellular transfer of
      OX40L molecules by a non-Ag specific manner. After 2-h coculture of activated
      CD4(+) T cell (OX40L(-), OX40(+)) with FLAG peptide-tagged OX40L (OX40L-flag)
      protein-expressing COS-1 cells, the OX40L-flag protein was detected on the cell
      surface of the CD4(+) T cells by both anti-OX40L and anti-FLAG mAbs. The
      intercellular OX40L transfer was specifically abrogated by pretreatment of the
      COS-1 cells with anti-OX40L mAb, 5A8. The OX40L transfer to OX40-negative cells
      was also observed, indicating an OX40-independent pathway of OX40L transfer.
      HUVECs, allostimulated monocytes, and human T cell leukemia virus type I-infected
      T cells, which all express OX40L, can potentially act as the donor cells of
      OX40L. The entire molecule of OX40L was transferred and stabilized on the
      recipient cell membrane with discrete punctate formation. The transferred OX40L
      on normal CD4(+) T cells was functionally active as they stimulated latent HIV-1
      infected cells to produce viral proteins via OX40 signaling. Therefore, these
      findings suggest that the intercellular molecular transfer of functional OX40L
      may be involved in modifying the immune responses.

PMID- 11441095
TI  - Regulation of MHC class II antigen presentation by sorting of recycling HLA-DM/DO
      and class II within the multivesicular body.
AB  - MHC class II molecules bind antigenic peptides in the late endosomal/lysosomal
      MHC class II compartments (MIIC) before cell surface presentation. The class II
      modulatory molecules HLA-DM and HLA-DO mainly localize to the MIICs. Here we show
      that DM/DO complexes continuously recycle between the plasma membrane and the
      lysosomal MIICs. Like DMbeta and the class II-associated invariant chain, the
      DObeta cytoplasmic tail contains potential lysosomal targeting signals. The
      DObeta signals, however, are not essential for internalization of the DM/DO
      complex from the plasma membrane or targeting to the MIICs. Instead, the DObeta
      tail determines the distribution of both DM/DO and class II within the
      multivesicular MIIC by preferentially localizing them to the limiting membrane
      and, in lesser amounts, to the internal membranes. This distribution augments the
      efficiency of class II antigenic peptide loading by affecting the efficacy of
      lateral interaction between DM/DO and class II molecules. Sorting of DM/DO and
      class II molecules to specific localizations within the MIIC represents a novel
      way of regulating MHC class II Ag presentation.

PMID- 11441096
TI  - Oxidative responses of human and murine macrophages during phagocytosis of
      Leishmania chagasi.
AB  - Leishmania chagasi, the cause of South American visceral leishmaniasis, must
      survive antimicrobial responses of host macrophages to establish infection.
      Macrophage oxidative responses have been shown to diminish in the presence of
      intracellular leishmania. However, using electron spin resonance we demonstrated
      that murine and human macrophages produce O2-during phagocytosis of opsonized
      promastigotes. Addition of the O2- scavenger 4-hydroxy-2,2,6,6
      tetramethylpiperidine-N-oxyl to cultures resulted in increased infection,
      suggesting that O2- enhances macrophage leishmanicidal activity. The importance
      of NO. produced by inducible NO synthase (iNOS) in controlling murine
      leishmaniasis is established, but its role in human macrophages has been debated.
      We detected NO. in supernatants from murine, but not human, macrophages infected
      with L. chagasi. Nonetheless, the iNOS inhibitor N(G)-monomethyl-L-arginine
      inhibited IFN-gamma-mediated intracellular killing by both murine and human
      macrophages. According to RNase protection assay and immunohistochemistry, iNOS
      mRNA and protein were expressed at higher levels in bone marrow of patients with
      visceral leishmaniasis than in controls. The iNOS protein also increased upon
      infection of human macrophages with L. chagasi promastigotes in vitro in the
      presence of IFN-gamma. These data suggest that O2- and NO. each contribute to
      intracellular killing of L. chagasi in human and murine macrophages.

PMID- 11441097
TI  - IFN-gamma overproduction and high level apoptosis are associated with high but
      not low virulence Toxoplasma gondii infection.
AB  - Toxoplasma gondii is an opportunistic intracellular parasite which induces a
      highly strong type 1 cytokine response. The present study focuses on defining the
      factors influencing the outcome of infection with tachyzoites of the type I,
      highly lethal RH strain, relative to the type II, low virulence strain ME49.
      Infection with the RH strain led to widespread parasite dissemination and rapid
      death of mice; in contrast, mice survived low virulence strain ME49 infection,
      and tachyzoite dissemination was much less extensive. Furthermore, massive
      apoptosis and disintegration of the splenic architecture was characteristic of
      RH, but not ME49, infection. In addition, hyperinduction of IFN-gamma and lack of
      NO production were found during RH, in contrast to ME49 infection. These data
      demonstrate that Toxoplasma strain characteristics exert a profound effect on the
      host immune response and that the latter itself is a crucial determinant in
      parasite virulence.

PMID- 11441098
TI  - Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression
      and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (MTB) induces vigorous immune responses, yet persists
      inside macrophages, evading host immunity. MTB bacilli or lysate was found to
      inhibit macrophage expression of class II MHC (MHC-II) molecules and MHC-II Ag
      processing. This report characterizes and identifies a specific component of MTB
      that mediates these inhibitory effects. The inhibitor was extracted from MTB
      lysate with Triton X-114, isolated by gel electroelution, and identified with Abs
      to be MTB 19-kDa lipoprotein. Electroelution- or immunoaffinity-purified MTB 19
      kDa lipoprotein inhibited MHC-II expression and processing of both soluble Ags
      and Ag 85B from intact MTB bacilli. Inhibition of MHC-II Ag processing by either
      MTB bacilli or purified MTB 19-kDa lipoprotein was dependent on Toll-like
      receptor (TLR) 2 and independent of TLR 4. Synthetic analogs of lipopeptides from
      Treponema pallidum also inhibited Ag processing. Despite the ability of MTB 19
      kDa lipoprotein to activate microbicidal and innate immune functions early in
      infection, TLR 2-dependent inhibition of MHC-II expression and Ag processing by
      MTB 19-kDa lipoprotein during later phases of macrophage infection may prevent
      presentation of MTB Ags and decrease recognition by T cells. This mechanism may
      allow intracellular MTB to evade immune surveillance and maintain chronic
      infection.

PMID- 11441099
TI  - A dominant role for Fc gamma receptors in antibody-dependent corneal
      inflammation.
AB  - Although production of specific Ab is a critical element of host defense, the
      presence of Ab in tissues leads to formation of immune complexes, which can
      trigger a type III Arthus reaction. Our studies on a mouse model of river
      blindness showed that Ab production is essential for recruitment of neutrophils
      and eosinophils to the cornea and for development of corneal opacification. In
      the current study, we determined the relative contribution of complement and
      FcgammaR interactions in triggering immune complex-mediated corneal disease.
      FcgammaR(-/-) mice, C3(-/-) mice, and immunocompetent control (B6/129Sj) mice
      were immunized s.c. and injected intrastromally with Onchocerca volvulus Ags.
      Slit lamp examination showed that control mice, C3(-/-) mice, and control mice
      injected with cobra venom factor developed pronounced corneal opacification,
      whereas corneas of FcgammaR(-/-) mice remained completely clear. Furthermore,
      recruitment of neutrophils and eosinophils to the corneal stroma was
      significantly impaired in FcgammaR(-/-) mice, but not in C3(-/-) mice or cobra
      venom factor-treated mice. We therefore conclude that FcgammaR-mediated cell
      activation, rather than complement activation, is the dominant pathway of immune
      complex disease in the cornea. These findings demonstrate a novel role for
      FcgammaR interactions in mediating ocular inflammation.

PMID- 11441100
TI  - Negative selection of T cells by Helicobacter pylori as a model for bacterial
      strain selection by immune evasion.
AB  - The majority of humans infected with Helicobacter pylori maintain a lifelong
      infection with strains bearing the cag pathogenicity island (PAI). H. pylori
      inhibits T cell responses and evades immunity so the mechanism by which infection
      impairs responsiveness was investigated. H. pylori caused apoptotic T cell death,
      whereas Campylobacter jejuni did not. The induction of apoptosis by H. pylori was
      blocked by an anti-Fas Ab (ZB4) or a caspase 8 inhibitor. In addition, a T cell
      line with the Fas rendered nonfunctional by a frame shift mutation was resistant
      to H. pylori-induced death. H. pylori strains bearing the cag PAI preferentially
      induced the expression of Fas ligand (FasL) on T cells and T cell death, whereas
      isogenic mutants lacking these genes did not. Inhibiting protein synthesis
      blocked FasL expression and apoptosis of T cells. Preventing the cleavage of FasL
      with a metalloproteinase inhibitor increased H. pylori-mediated killing. Thus, H.
      pylori induced apoptosis in Fas-bearing T cells through the induction of FasL
      expression. Moreover, this effect was linked to bacterial products encoded by the
      cag PAI, suggesting that persistent infection with this strain may be favored
      through the negative selection of T cells encountering specific H. pylori Ags.

PMID- 11441101
TI  - Regulation of complement classical pathway by association of C4b-binding protein
      to the surfaces of SK-OV-3 and Caov-3 ovarian adenocarcinoma cells.
AB  - The role of fluid-phase regulators of complement is to inhibit excessive
      complement activation and maintain homeostasis in blood. By binding to and
      inactivating complement components on cell surfaces, they can also protect
      autologous cells from complement-mediated cytotoxicity and phagocytosis. In this
      study, we wanted to find out whether C4b-binding protein (C4bp), a fluid-phase
      regulator of the classical complement pathway, could directly bind to cell
      surfaces in a functionally active form. After screening several malignant cell
      lines, we observed that the ovarian adenocarcinoma cell lines SK-OV-3, Caov-3,
      and SW626 were capable of binding C4bp. Binding tests with recombinant deletion
      mutants suggested that the primary binding site on C4bp is located on the alpha
      chain complement control protein 4 domain. Functional tests showed that tumor
      cell-bound C4bp retained its cofactor activity for factor I-mediated inactivation
      of C4b, thus increasing the control of classical complement pathway activation on
      the surfaces of these cells. These results demonstrate a novel mechanism of
      complement regulation on cell surfaces, particularly on those of malignant
      ovarian tumor cells.

PMID- 11441102
TI  - Modulation of macrophage cytokine production by ES-62, a secreted product of the
      filarial nematode Acanthocheilonema viteae.
AB  - Parasite survival and host health may depend on the ability of the parasite to
      modulate the host immune response by the release of immunomodulatory molecules.
      Excretory-secretory (ES)-62, one such well-defined molecule, is a major secreted
      protein of the rodent filarial nematode Acanthocheilonema viteae, and has
      homologues in human filarial nematodes. Previously we have shown that ES-62 is
      exclusively associated with a Th2 Ab response in mice. Here we provide a
      rationale for this polarized immune response by showing that the parasite
      molecule suppresses the IFN-gamma/LPS-induced production, by macrophages, of
      bioactive IL-12 (p70), a key cytokine in the development of Th1 responses. This
      suppression of the induction of a component of the host immune response extends
      to the production of the proinflammatory cytokines IL-6 and TNF-alpha, but not
      NO. The molecular mechanism underlying these findings awaits elucidation but,
      intriguingly, the initial response of macrophages to ES-62 is to demonstrate a
      low and transient release of these cytokines before becoming refractory to
      further release induced by IFN-gamma/LPS. The relevance of our observations is
      underscored by the finding that macrophages recovered from mice exposed to
      "physiological" levels of ES-62 by the novel approach of continuous release from
      implanted osmotic pumps in vivo were similarly refractory to release of IL-12,
      TNF-alpha, IL-6, but not NO, ex vivo. Therefore, our results suggest that
      exposure to ES-62 renders macrophages subsequently unable to produce
      Th1/proinflammatory cytokines. This likely contributes to the generation of
      immune responses with an anti-inflammatory Th2 phenotype, a well-documented
      feature of filarial nematode infection.

PMID- 11441103
TI  - Overexpression of IL-15 in vivo enhances protection against Mycobacterium bovis
      bacillus Calmette-Guerin infection via augmentation of NK and T cytotoxic 1
      responses.
AB  - To investigate the immunomodulating effects of IL-15 in vivo on mycobacterial
      infection, we used IL-15-transgenic (Tg) mice, which were recently constructed
      with cDNA-encoding secretable isoform of IL-15 precursor protein under the
      control of a MHC class I promoter. The IL-15-Tg mice exhibited resistance against
      infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG), as assessed by
      bacteria growth. IFN-gamma level in serum was significantly higher in IL-15-Tg
      mice than in non-Tg mice after BCG infection. NK cells were remarkably increased,
      and Ag-specific T cytotoxic 1 response mediated by CD8+ T cells producing IFN
      gamma was significantly augmented in the IL-15-Tg mice following BCG infection.
      Neutralization of endogenous IFN-gamma by in vivo administration of anti-IFN
      gamma mAb deteriorated the clearance of the bacteria. Depletion of of NK cells or
      CD8+ T cells by in vivo administration of anti-asialo-GM(1) Ab or anti-CD8 mAb
      hampered the exclusion of bacteria. Thus, overexpression of IL-15 in vivo
      enhanced protection against BCG infection via augmentation of NK and T cytotoxic
      1 responses.

PMID- 11441104
TI  - IL-12/IL-18-dependent IFN-gamma release by murine dendritic cells.
AB  - Dendritic cells (DC) develop in GM-CSF-stimulated cultures from murine bone
      marrow progenitors in serum-free (or low serum) medium. CD11c(+) myeloid DC from
      7-day cultures stimulated with TNF-alpha, IFN-alpha, IFN-gamma, or LPS up
      regulated surface expression of CD40 and CD86 costimulator and MHC class II
      molecules, did not up-regulate the low "spontaneous" release of IL-18, and did
      not release IFN-gamma. Stimulation of in vitro-generated DC with exogenous IL-12
      and IL-18 (but not with IL-4 or LPS plus IL-18) induced IFN-gamma expression and
      release in 15-20% of the DC (detectable by FACS analyses or ELISA). Endogenous IL
      12 p70 produced by DC in response to ligation of CD40 stimulated IFN-gamma
      release when exogenous IL-18 was supplied. In vivo-generated, splenic CD8alpha(+)
      and CD8alpha(-) DC (from immunocompetent and immunodeficient H-2(d) and H-2(b)
      mice) cultured with IL-12 and IL-18 released IFN-gamma. The presence of LPS
      during the stimulation of DC with IL-18 plus endogenous (CD40 ligation) or
      exogenous IL-12 did not affect their IFN-gamma release. In contrast, splenic DC
      pretreated in vitro or in vivo by LPS strikingly down-regulated IFN-gamma release
      in response to stimulation by IL-18 and (endogenous or exogenous) IL-12. Hence,
      DC are a source of early IFN-gamma generated in response to a cascade of cytokine
      and/or cell-derived signals that can be positively and negatively regulated.

PMID- 11441105
TI  - Inhibition of endotoxin-induced macrophage chemokine production by vasoactive
      intestinal peptide and pituitary adenylate cyclase-activating polypeptide in
      vitro and in vivo.
AB  - Inflammatory chemokines recruit various populations of immune cells that initiate
      and maintain the inflammatory response against foreign Ags. Although such a
      response is necessary for the elimination of the Ag, the inflammation has to be
      eventually resolved in a healthy organism. Neuropeptides such as vasoactive
      intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide
      (PACAP), released after antigenic stimulation, contribute to the termination of
      an inflammatory response primarily by inhibiting the production of
      proinflammatory cytokines. Here we investigated the effects of VIP and PACAP on
      chemokine production. We report that VIP and PACAP inhibit the expression of the
      macrophage-derived CXC chemokines macrophage inflammatory protein-2 and KC (IL
      8), and of the CC chemokines MIP-1alpha, MIP-1beta, monocyte chemoattractant
      protein 1, and RANTES in vivo and in vitro. The inhibition of chemokine gene
      expression correlates with an inhibitory effect of VIP/PACAP on NF-kappaB binding
      and transactivating activity. The VIP/PACAP inhibition of both chemokine
      production and of NF-kappaB binding and transactivating activity is mediated
      through the specific VIP receptor VPAC1, and involves both cAMP-dependent and 
      independent intracellular pathways. In an in vivo model of acute peritonitis, the
      inhibition of chemokine production by VIP/PACAP leads to a significant reduction
      in the recruitment of polymorphonuclear cells, macrophages, and lymphocytes into
      the peritoneal cavity. These findings support the proposed role of VIP and PACAP
      as key endogenous anti-inflammatory agents and describe a novel mechanism, i.e.,
      the inhibition of the production of macrophage-derived chemokines.

PMID- 11441106
TI  - Glucocorticoid augmentation of macrophage capacity for phagocytosis of apoptotic
      cells is associated with reduced p130Cas expression, loss of paxillin/pyk2
      phosphorylation, and high levels of active Rac.
AB  - Phagocytic clearance of apoptotic granulocytes has a pivotal role in determining
      an inflammatory outcome, resolution or progression to a chronic state associated
      with development of fibrotic repair mechanisms, and/or autoimmune responses. In
      this study, we describe reprogramming of monocyte to macrophage differentiation
      by glucocorticoids, resulting in a marked augmentation of their capacity for
      phagocytosis of apoptotic neutrophils. This monocyte/macrophage phenotype was
      characterized by decreased phosphorylation, and therefore recruitment of paxillin
      and pyk2 to focal contacts and a down-regulation of p130Cas, a key adaptor
      molecule in integrin adhesion signaling. Glucocorticoid-treated cells also
      displayed higher levels of active Rac and cytoskeletal activity, which were
      mirrored by increases in phagocytic capability for apoptotic neutrophils. We
      propose that changes in the capacity for reorganization of cytoskeletal elements
      induced by glucocorticoids are essential for efficient phagocytic uptake of
      apoptotic cells.

PMID- 11441107
TI  - Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble
      tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein:
      role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll
      like receptor 2 signaling.
AB  - Toll-like receptor 2 (TLR2) and TLR4 play important roles in innate immune
      responses to various microbial agents. We have previously shown that human dermal
      endothelial cells (HMEC) express TLR4, but very little TLR2, and respond to LPS,
      but not to Mycobacterium tuberculosis 19-kDa lipoprotein, unless transfected with
      TLR2. Here we report that HMEC are unresponsive to several additional
      biologically relevant TLR2 ligands, including, phenol-soluble modulin (PSM), a
      complex of three small secreted polypeptides from the skin commensal
      Staphylococcus epidermidis, soluble tuberculosis factor (STF), and Borrelia
      burgdorferi outer surface protein A lipoprotein (OspA-L). Expression of TLR2
      renders HMEC responsive to all these ligands. We further characterized the
      signaling pathway in response to STF, OspA-L, and PSM in TLR2-transfected HMEC.
      The TLR2 signaling pathway for NF-kappaB trans-activation shares the IL-1R
      signaling molecules. Dominant negative constructs of TLR2 or TLR6 inhibit the
      responses of STF and OspA-L as well as PSM in TLR2-transfected HMEC, supporting
      the concept of functional cooperation between TLR2 and TLR6 for all these TLR2
      ligands. Moreover, we show that Toll-interacting protein (Tollip)
      coimmunoprecipitates with TLR2 and TLR4 using HEK 293 cells, and overexpression
      of Tollip inhibits NF-kappaB activation in response to TLR2 and TLR4 signaling.
      Collectively, these findings suggest that there is functional interaction between
      TLR2 and TLR6 in the cellular response to STF and OspA-L in addition to S.
      epidermidis (PSM) Ags, and that engagement of TLR2 triggers a signaling cascade,
      which shares the IL-1R signaling molecules, similar to the TLR4-LPS signaling
      cascade. Our data also suggest that Tollip may be an important constituent of
      both the TLR2 and TLR4 signaling pathways.

PMID- 11441108
TI  - Human eosinophils and human high affinity IgE receptor transgenic mouse
      eosinophils express low levels of high affinity IgE receptor, but release IL-10
      upon receptor activation.
AB  - FcepsilonRI expressed by human eosinophils is involved in IgE-mediated
      cytotoxicity reactions toward the parasite Schistosoma mansoni in vitro. However,
      because receptor expression is low on these cells, its functional role is still
      controversial. In this study, we have measured surface and intracellular
      expression of FcepsilonRI by blood eosinophils from hypereosinophilic patients
      and normal donors. The number of unoccupied receptors corresponded to
      approximately 4,500 Ab binding sites per cell, whereas 50,000 Ab binding sites
      per cell were detected intracellularly. Eosinophils from patients displayed
      significantly more unoccupied receptors than cells from normal donors. This
      number correlated to both serum IgE concentrations and to membrane-bound IgE. The
      lack of FcepsilonRI expression by mouse eosinophils has hampered further studies.
      To overcome this fact and experimentally confirm our findings on human
      eosinophils, we engineered IL-5 x hFcepsilonRIalpha double-transgenic mice, whose
      bone marrow, blood, spleen, and peritoneal eosinophils expressed FcepsilonRI
      levels similar to levels of human eosinophils, after 4 days culture with IgE in
      the presence of IL-5. Both human and mouse eosinophils were able to secrete IL-10
      upon FcepsilonRI engagement. Thus, comparative analysis of cells from patients
      and from a relevant animal model allowed us to clearly demonstrate that
      FcepsilonRI-mediated eosinophil activation leads to IL-10 secretion. Through
      FcepsilonRI expression, these cells are able to contribute to both the regulation
      of the immune response and to its effector mechanisms.

PMID- 11441109
TI  - IL-1-independent role of IL-17 in synovial inflammation and joint destruction
      during collagen-induced arthritis.
AB  - T cell IL-17 displays proinflammatory properties and is expressed in the synovium
      of patients with rheumatoid arthritis. Its contribution to the arthritic process
      has not been identified. Here, we show that blocking of endogenous IL-17 in the
      autoimmune collagen-induced arthritis model results in suppression of arthritis.
      Also, joint damage was significantly reduced. In contrast, overexpression of IL
      17 enhanced collagen arthritis. Moreover, adenoviral IL-17 injected in the knee
      joint of type II collagen-immunized mice accelerated the onset and aggravated the
      synovial inflammation at the site. Radiographic and histologic analysis showed
      markedly increased joint destruction. Elevated levels of IL-1beta protein were
      found in synovial tissue. Intriguingly, blocking of IL-1alphabeta with
      neutralizing Abs had no effect on the IL-17-induced inflammation and joint damage
      in the knee joint, implying an IL-1 independent pathway. This direct potency of
      IL-17 was underscored in the unabated IL-17-induced exaggeration of bacterial
      cell wall-induced arthritis in IL-1beta(-/-) mice. In conclusion, this data shows
      that IL-17 contributes to joint destruction and identifies an IL-1-independent
      role of IL-17. These findings suggest IL-17 to be a novel target for the
      treatment of destructive arthritis and may have implications for tissue
      destruction in other autoimmune diseases.

PMID- 11441110
TI  - Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor
      2 expressed by lung epithelial cells.
AB  - The respiratory epithelium represents the first barrier encountered by airborne
      Ags. Two major dust mite Ags, Der p3 and Der p9, are serine proteases that may
      activate lung epithelial cells by interaction with the protease-activated
      receptor 2 (PAR-2). In this study both Der p3 and Der p9 cleaved the peptide
      corresponding to the N terminus of PAR-2 at the activation site. Both Ags
      sequentially stimulated phosphoinositide hydrolysis, transient cytosolic Ca(2+)
      mobilization, and release of GM-CSF and eotaxin in human pulmonary epithelial
      cells. These responses were similar to those observed with trypsin and a specific
      PAR-2 agonist and were related to the serine protease activity of Der p3 and Der
      p9. Cell exposure to the Ags resulted in a refractory period, indicating that a
      PAR had been cleaved. Partial desensitization to Der p3 and Der p9 by the PAR-2
      agonist suggested that PAR-2 was one target of the Ags. However, PAR-2 was not
      the only target, because the PAR-2 agonist caused less desensitization to Der p3
      and Der p9 than did trypsin. A phospholipase C inhibitor prevented the cytokine
      releasing effect of the PAR-2 agonist and abolished or reduced (>70%) the
      cytokine-releasing effects of Der p3 and Der p9. Our results suggest that Der p 3
      and Der p9 may induce a nonallergic inflammatory response in the airways through
      the release of proinflammatory cytokines from the bronchial epithelium and that
      this effect is at least in part mediated by PAR-2.

PMID- 11441111
TI  - Distinct tissue site-specific requirements of mast cells and complement
      components C3/C5a receptor in IgG immune complex-induced injury of skin and lung.
AB  - We induced the passive reverse Arthus reaction to IgG immune complexes (IC) at
      different tissue sites in mice lacking C3 treated or not with a C5aR-specific
      antagonist, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared
      the inflammatory responses with those in the corresponding wild-type mice. We
      confirmed that IC inflammation of skin can be mediated largely by mast cells
      expressing C5aR and FcgammaRIII. In addition, we provided evidence for C3
      independent C5aR triggering, which may explain why the cutaneous Arthus reaction
      develops normally in C3(-/-) mice. Furthermore, some, but not all, of the acute
      changes associated with the Arthus response in the lung were significantly more
      intense in normal mice than in C3(-/-) or Kit(W)/Kit(W-v) mice, indicating for C3
      and mast cell-dependent and -independent components. Finally, we demonstrated
      that C3 contributed to the elicitation of neutrophils to alveoli, which
      corresponded to an increased synthesis of TNF-alpha, macrophage-inflammatory
      protein-2, and cytokine-induced neutrophil chemoattractant. While mast cells
      similarly influenced alveolar polymorphonuclear leukocyte influx, the levels of
      these cytokines remained largely unaffected in mast cell deficiency. Together,
      the phenotypes of C3(-/-) mice and Kit(W)/Kit(W-v) mice suggest that complement
      and mast cells have distinct tissue site-specific requirements acting by
      apparently distinct mechanisms in the initiation of IC inflammation.

PMID- 11441112
TI  - Differential regulation of chemokine production in human peritoneal mesothelial
      cells: IFN-gamma controls neutrophil migration across the mesothelium in vitro
      and in vivo.
AB  - Leukocyte recruitment into the infected peritoneal cavity consists of an early,
      predominant polymorphonuclear leukocyte (PMN) influx and subsequent, prolonged
      mononuclear cell migration phase. Although chemokine secretion by resident
      peritoneal cells plays a primary role in mediating this migration, the mechanisms
      involved in controlling the switch in phenotype of cell infiltrate remain
      unclear. The present study investigates a potential role for the Th1-type
      cytokine IFN-gamma in the process of leukocyte recruitment into the peritoneal
      cavity. Stimulation of cultured human peritoneal mesothelial cells with IFN-gamma
      (1-100 U/ml) alone or in combination with IL-1beta (100 pg/ml) or TNF-alpha (1000
      pg/ml) resulted in significant up-regulation of monocyte chemoattractant protein
      1 and RANTES protein secretion. In contrast, IFN-gamma inhibited basal and IL
      1beta-, and TNF-alpha-induced production of IL-8. The modulating effects of IFN
      gamma on chemokine production occurred at the level of gene expression, and the
      degree of regulation observed was dependent on the doses of IL-1beta and TNF
      alpha used. Analysis of the functional effects of IFN-gamma on IL-1beta-induced
      transmesothelial PMN migration with an in vitro human transmigration system and
      an in vivo murine model of peritoneal inflammation demonstrated that IFN-gamma
      was able to down-regulate PMN migration induced by optimal doses of IL-1beta.
      These effects were mediated in vivo via down-regulation of CXC chemokine
      synthesis. These findings suggest that IFN-gamma may play a role in controlling
      the phenotype of infiltrating leukocyte during the course of an inflammatory
      response, in part via regulation of resident cell chemokine synthesis.

PMID- 11441113
TI  - Functional expression of IL-12 receptor by human eosinophils: IL-12 promotes
      eosinophil apoptosis.
AB  - In murine models of allergic inflammation, IL-12 has been shown to decrease
      tissue eosinophilia, but the underlying mechanisms are not known. We evaluated
      the expression of IL-12R and the effect of IL-12 on eosinophil survival. In situ
      hybridization demonstrated the presence of mRNA and immunoreactivity for IL
      12Rbeta1 and -beta2 subunits in human peripheral blood eosinophils. Surface
      expression of IL-12Rbeta1 and -beta2 subunits on freshly isolated human
      eosinophils was optimally expressed after incubation with PMA. To determine the
      functional significance of IL-12R studies, we studied cell viability and
      apoptosis. Morphological analysis and propidium iodide staining for cell cycle
      demonstrated that recombinant human IL-12 increased in vitro human eosinophil
      apoptosis in a dose-dependent manner. Addition of IL-5 together with IL-12
      abrogated eosinophil apoptosis, suggesting that IL-12 and IL-5 have antagonistic
      effects. Our findings provide evidence for a novel role for IL-12 in regulating
      eosinophil function by increasing eosinophil apoptosis.

PMID- 11441114
TI  - Tissue-type plasminogen activator deficiency exacerbates arthritis.
AB  - Fibrin deposition, cell migration, and tissue remodeling are key components in
      the lesions of inflammatory joint diseases, such as rheumatoid arthritis. The
      plasminogen activators (PAs), namely, tissue-type PA (t-PA) and urokinase PA, are
      implicated in these aspects of an inflammatory response, although their precise
      roles are yet to be defined. We therefore used gene-deficient mice to explore
      their role in a two-stage arthritis model involving intraarticular methylated BSA
      injection, followed by systemic IL-1 treatment. We report in this study that both
      t-PA and urokinase PA are protective for the mild arthritis induced by
      intraarticular methylated BSA injection alone, since absence of either of them
      exacerbates the response; following s.c. IL-1 injection, t-PA(-/-) mice had
      particularly severe disease. Fibrin deposition appeared to parallel disease
      severity under the various conditions, suggesting that PA-mediated fibrinolysis
      may be normally playing a protective role in inflammatory joint disease.

PMID- 11441115
TI  - Adenoviral delivery of human and viral IL-10 in murine sepsis.
AB  - Adenovirus (Ad) gene therapy has been proposed as a drug-delivery system for the
      targeted administration of protein-based therapies, including growth factors and
      biological response modifiers. However, inflammation associated with Ad
      transduction has raised concern about its safety and efficacy in acute
      inflammatory diseases. In the present report, intratracheal and i.v.
      administration of a first-generation adenoviral recombinant (E1,E3 deleted)
      either containing an empty cassette or expressing the anti-inflammatory cytokines
      viral or human IL-10 (IL-10) was administered to mice subjected to zymosan
      induced multisystem organ failure or to acute necrotizing pancreatitis.
      Pretreatment of mice with the intratracheal instillation of Ad expressing human
      IL-10 or viral IL-10 reduced weight loss, attenuated the proinflammatory cytokine
      response, and reduced mortality in the zymosan-induced model, whereas
      pretreatment with a control adenoviral recombinant did not significantly
      exacerbate the response. Pretreatment of mice with pancreatitis using adenoviral
      vectors expressing IL-10 significantly reduced the degree of pancreatic and liver
      injury and liver inflammation when administered systemically, but not
      intratracheally. We conclude that adenoviral vectors can be administered
      prophylactically in acute inflammatory syndromes, and expression of the anti
      inflammatory protein IL-10 can be used to suppress the underlying inflammatory
      process.

PMID- 11441116
TI  - Respiratory syncytial virus predisposes mice to augmented allergic airway
      responses via IL-13-mediated mechanisms.
AB  - The development of severe childhood asthma may be influenced by several factors
      including environmental and infectious stimuli. The causal relationship between
      infectious viral responses, such as respiratory syncytial virus (RSV), and severe
      asthma during early childhood is unclear. In these studies, the ability for an
      initial RSV infection to exacerbate and promote a more severe asthmatic-type
      response was investigated by combining established murine models of disease. We
      examined the ability of RSV to induce exacerbation of allergic disease over a
      relatively long period, leading to development of severe airway responses
      including airway inflammation and hyperreactivity. The preferential production of
      IL-13 during a primary RSV infection appears to play a critical role for the
      exacerbation of cockroach allergen-induced disease. The depletion of IL-13 during
      RSV infections inhibited the exacerbation and acceleration of severe allergen
      induced airway hyperreactivity. This was indicated by decreases in airway
      hyperreactivity and changes in lung chemokine production. These data suggest that
      the airway responses during asthma can be greatly affected by a previous RSV
      infection, even when infection occurs before allergen sensitization. Overall,
      infection of the airways with RSV can induce an IL-13-dependent change in airway
      function and promotes an environment that contributes to the development of
      severe allergic asthmatic responses.

PMID- 11441117
TI  - H-2D end confers dominant protection from IL-10-mediated acceleration of
      autoimmune diabetes in the nonobese diabetic mouse.
AB  - BALB/c mice that express IL-10 as a transgene in their pancreatic beta cells (Ins
      IL-10 mice) do not develop diabetes, even after crossing to nonobese diabetic
      (NOD) mice ((Ins-IL-10 x NOD)F(1) mice). However, backcross of F(1) mice to NOD
      mice (NOD.Ins-IL-10 mice) results in N2 and N3 generations that develop
      accelerated diabetes. In this study, we found that NOD.Ins-IL-10 mice that
      expressed BALB/c-derived MHC molecules (NOD.Ins-IL-10(H-2(g7/d)) mice) were
      protected from diabetes. This protection associated with peri-islet infiltration
      and preserved beta cell function. Moreover, expression of I-A(d) and I-E(d) MHC
      class II molecules of BALB/c origin was not responsible for protection, but
      NOD.Ins-IL-10 mice that expressed BALB/c MHC class I D(d) molecules (NOD.Ins-IL
      10(H-2(g7/d)) mice) did not develop diabetes. To directly test the possibility of
      a protective role of H-2D(d) in the development of accelerated diabetes, we
      generated transgenic mice expressing D(d) under the control of the MHC class I
      promoter. We found that double transgenic NOD.Ins-IL-10-D(d) mice developed
      accelerated diabetes in a fashion similar to NOD.Ins-IL-10 mice that were D(d)
      negative. Microsatellite analysis of H-2D(d)-linked loci confirmed association
      between BALB/c-derived alleles and protection of NOD.Ins-IL-10(H-2(g7/d)) mice.
      These results suggest a control of H-2D(d)-linked gene(s) on IL-10-mediated
      acceleration of autoimmune diabetes and dominant protection of the D(d) region in
      NOD.Ins-IL-10 mice.

PMID- 11441118
TI  - Lymphoid neogenesis in rheumatoid synovitis.
AB  - In rheumatoid arthritis (RA), tissue-infiltrating lymphocytes can be arranged in
      sophisticated organizations that resemble microstructures usually formed in
      secondary lymphoid organs. Molecular pathways and host risk factors involved in
      this process of lymphoid neogenesis remain to be defined. In a series of 64
      synovial tissue biopsies, lymphoid follicles with germinal centers (GCs) were
      found in 23.4% of the patients. Follicular dendritic cells (FDCs) were
      exclusively present in tissues with GCs, suggesting that the recruitment or in
      situ maturation of FDCs is a critical factor for GC formation in the synovial
      membrane. Primary follicles were absent, emphasizing the role of Ag recognition
      in the generation of inflammation-associated lymphoid organogenesis. Multivariate
      logistic regression analysis of tissue cytokines and chemokines identified two
      parameters, in situ transcription of lymphotoxin (LT)-beta and of B lymphocyte
      chemoattractant (BLC; BLC/CXCL13), that were predictors for FDC recruitment and
      synovial GC formation. LT-beta and BLC/CXCL13 were found to be independent
      variables that could, in part, compensate for each other to facilitate GC
      formation. Prediction models incorporating in situ transcription of LT-beta and
      BLC/CXCL13 had high negative yet moderate positive predictive values, suggesting
      that LT-beta and BLC/CXCL13 are necessary but not sufficient. LT-beta protein was
      detected on a subset of mantle zone and GC B cells, but also on T cells in
      follicular structures. BLC/CXCL13 was produced by FDCs in follicular centers, but
      was predominantly found in endothelial cells and synovial fibroblasts, suggesting
      heterotypic signaling between cells of the synovial membrane and infiltrating
      lymphocytes in regulating extranodal lymphoid neogenesis.

PMID- 11441119
TI  - Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent
      autoimmune diabetes in nonobese diabetic mice.
AB  - B cells can serve dual roles in modulating T cell immunity through their potent
      capacity to present Ag and induce regulatory tolerance. Although B cells are
      necessary components for the initiation of spontaneous T cell autoimmunity to
      beta cell Ags in nonobese diabetic (NOD) mice, the role of activated B cells in
      the autoimmune process is poorly understood. In this study, we show that LPS
      activated B cells, but not control B cells, express Fas ligand and secrete TGF
      beta. Coincubation of diabetogenic T cells with activated B cells in vitro leads
      to the apoptosis of both T and B lymphocytes. Transfusion of activated B cells,
      but not control B cells, into prediabetic NOD mice inhibited spontaneous Th1
      autoimmunity, but did not promote Th2 responses to beta cell autoantigens.
      Furthermore, this treatment induced mononuclear cell apoptosis predominantly in
      the spleen and temporarily impaired the activity of APCs. Cotransfer of activated
      B cells with diabetogenic splenic T cells prevented the adoptive transfer of type
      I diabetes mellitus (T1DM) to NOD/scid mice. Importantly, whereas 90% of NOD mice
      treated with control B cells developed T1DM within 27 wk, <20% of the NOD mice
      treated with activated B cells became hyperglycemic up to 1 year of age. Our data
      suggest that activated B cells can down-regulate pathogenic Th1 immunity through
      triggering the apoptosis of Th1 cells and/or inhibition of APC activity by the
      secretion of TGF-beta. These findings provide new insights into T-B cell
      interactions and may aid in the design of new therapies for human T1DM.

PMID- 11441120
TI  - CD4+ T cells engrafted with a recombinant immunoreceptor efficiently lyse target
      cells in a MHC antigen- and Fas-independent fashion.
AB  - T cells engrafted by a recombinant immunoreceptor with predefined Ag specificity
      can efficiently lyse Ag-positive target cells in a MHC Ag-independent manner. It
      is yet unresolved how receptor-grafted CD4+ T cells contribute to MHC Ag
      independent target cell lysis. To address this issue, we grafted isolated CD8+
      and CD4+ T cells from the peripheral blood with recombinant anti-carcinoembryonic
      Ag and anti-CD30 receptors, respectively. Cytotoxicity analyses revealed that
      grafted CD4+ T cells exert cytolysis of Ag-positive target cells with an
      efficiency similar to that of grafted CD8+ T cells. Lysis by receptor-grafted
      CD4+ T cells is Ag specific and is inhibited by blocking the target Ag or the Ag
      binding site of the recombinant receptor. Both Fas-sensitive and Fas-resistant
      target cells are lysed with equal efficiency, and lysis of Fas-sensitive target
      cells is not blocked by an anti-Fas ligand Ab, indicating that cytolysis by
      receptor-grafted CD4+ T cells is independent of the Fas pathway. We conclude that
      cytolysis by CD4+ T cells equipped with a recombinant immunoreceptor is MHC Ag
      and Fas independent and likely to be mediated by perforin present in receptor
      grafted CD4+ T cells.

PMID- 11441121
TI  - Immunofluorescence detection of delta opioid receptors (DOR) on human peripheral
      blood CD4+ T cells and DOR-dependent suppression of HIV-1 expression.
AB  - The delta opioid receptors (DORs) modulate T cell proliferation, IL-2 production,
      chemotaxis, and intracellular signaling. Moreover, in DOR-transfected Jurkat
      cells, delta opioids have been shown to suppress HIV-1 p24 Ag expression. These
      observations led us to characterize the expression of DORs by human peripheral
      blood T cells and to determine whether a specific DOR agonist, benzamide,4-([2,5
      dimethyl-4-(2-propenyl)-1-piperazinyl](3-methoxyphenyl)methyl]-N,
      ,(2S[1(S*),2alpha,5beta])-(9Cl) (SNC-80), can suppress p24 Ag expression by HIV-1
      infected CD4+ T cells obtained from normal donors. By immunofluorescence flow
      cytometry, PHA stimulated the expression of DOR from 1.94 +/- 0.70 (mean +/- SEM)
      to 20.70 +/- 1.88% of the PBMC population by 48 h (p < 0.0001). DOR expression
      was approximately 40% of both the PHA-stimulated CD4+ and CD8+ T cell subsets,
      and virtually all DORs were found on these subsets. To determine whether
      activated DORs suppress HIV-1 expression, PBMC were prestimulated with PHA, and
      then CD4+ T cells were purified, pretreated with SNC-80, and infected with HIV-1.
      In a concentration-dependent manner, SNC-80 inhibited production of p24 Ag. SNC
      80 10(-10) M maximally suppressed (approximately 50%) both lymphocytotropic (HIV
      1 MN) and monocytotropic (SF162) strains; higher concentrations were less
      effective. Naltrindole, a selective DOR antagonist, abolished the inhibitory
      effects of SNC-80. Kinetic studies indicated that 24-h pre- or postincubation
      with SNC-80, relative to infection with HIV-1, eliminated its suppressive
      effects. Thus, stimulating the DORs expressed by activated CD4+ T cells
      significantly suppressed the expression of HIV-1. These findings suggest that
      opioid immunomodulation directed at host T cells may be adjunctive to standard
      antiviral approaches to HIV-1 infection.

PMID- 11441122
TI  - Costimulation blockade, busulfan, and bone marrow promote titratable
      macrochimerism, induce transplantation tolerance, and correct genetic
      hemoglobinopathies with minimal myelosuppression.
AB  - Mixed hemopoietic chimerism has the potential to correct genetic hemological
      diseases (sickle cell anemia, thalassemia) and eliminate chronic
      immunosuppressive therapy following organ transplantation. To date, most
      strategies require either recipient conditioning (gamma-irradiation, depletion of
      the peripheral immune system) or administration of "mega" doses of bone marrow to
      facilitate reliable engraftment. Although encouraging, many issues remain that
      may restrict or prevent clinical application of such strategies. We describe an
      alternative, nonirradiation based strategy using a single dose of busulfan,
      costimulation blockade, and T cell-depleted donor bone marrow, which promotes
      titratable macrochimerism and a reshaping of the T cell repertoire. Chimeras
      exhibit robust donor-specific tolerance, evidenced by acceptance of fully
      allogeneic skin grafts and failure to generate donor-specific proliferative
      responses in an in vivo graft-versus-host disease model of alloreactivity. In
      this model, donor cell infusion and costimulation blockade without busulfan were
      insufficient for tolerance induction as donor-specific IFN-gamma-producing T
      cells re-emerged and skin grafts were rejected at approximately 100 days. When
      applied to a murine beta-thalassemia model, this approach allows for the
      normalization of hemologic parameters and replacement of the diseased red cell
      compartment. Such a protocol may allow for clinical application of mixed
      chimerism strategies in patients with end-stage organ disease or
      hemoglobinopathies.

PMID- 11441123
TI  - Defective CD8+ T cell peripheral tolerance in nonobese diabetic mice.
AB  - Nonobese diabetic (NOD) mice develop spontaneous autoimmune diabetes that
      involves participation of both CD4+ and CD8+ T cells. Previous studies have
      demonstrated spontaneous reactivity to self-Ags within the CD4+ T cell
      compartment in this strain. Whether CD8+ T cells in NOD mice achieve and maintain
      tolerance to self-Ags has not previously been evaluated. To investigate this
      issue, we have assessed the extent of tolerance to a model pancreatic Ag, the
      hemagglutinin (HA) molecule of influenza virus, that is transgenically expressed
      by pancreatic islet beta cells in InsHA mice. Previous studies have demonstrated
      that BALB/c and B10.D2 mice that express this transgene exhibit tolerance of HA
      and retain only low-avidity CD8+ T cells specific for the dominant peptide
      epitope of HA. In this study, we present data that demonstrate a deficiency in
      peripheral tolerance within the CD8+ T cell repertoire of NOD-InsHA mice. CD8+ T
      cells can be obtained from NOD-InsHA mice that exhibit high avidity for HA, as
      measured by tetramer (K(d)HA) binding and dose titration analysis. Significantly,
      these autoreactive CD8+ T cells can cause diabetes very rapidly upon adoptive
      transfer into NOD-InsHA recipient mice. The data presented demonstrate a
      retention in the repertoire of CD8+ T cells with high avidity for islet Ags that
      could contribute to autoimmune diabetes in NOD mice.

PMID- 11441124
TI  - Acetylcholine receptor peptide recognition in HLA DR3-transgenic mice: in vivo
      responses correlate with MHC-peptide binding.
AB  - HLA DR3 is an MHC molecule that reportedly predisposes humans to myasthenia
      gravis (MG). Though MG is an Ab-mediated autoimmune disease, CD4+ T cells are
      essential for the generation of high-affinity Abs; hence the specificities of
      autoreactive CD4+ T cells are important. In this study we report the HLA DR3
      restricted T cell determinants on the extracellular region sequence of human
      acetylcholine receptor alpha subunit. We find two promiscuous determinants on
      this region 141-160 and 171-190 as defined by their immunogenicity in HLA DR3-,
      HLA DQ8-, and HLA DQ6-transgenic mice in the absence of endogenous mouse class II
      molecules. We also studied the minimal determinants of these two regions by
      truncation analysis, and the MHC binding affinity of a set of overlapping
      peptides spanning the complete sequence region of human acetylcholine receptor
      alpha subunit. One of the peptide sequences strongly immunogenic in HLA DR3
      transgenic mice also had the highest binding affinity to HLA DR3. Identification
      of T cell determinants restricted to an MHC molecule known to predispose to MG
      may be an important step toward the development of peptide-based immunomodulation
      strategies for this autoimmune disease.

PMID- 11441125
TI  - Failure to induce neonatal tolerance in mice that lack both IL-4 and IL-13 but
      not in those that lack IL-4 alone.
AB  - Current evidence suggests that neonatal tolerance to a foreign Ag is the
      consequence of IL-4-mediated Th2 immunity rather than the thymic deletion of Ag
      specific T cells. Here, we addressed the role of IL-4 in neonatal tolerance by
      testing whether tolerance to a minor histocompatibility Ag can be induced in
      newborn mice that lack IL-4 (IL-4(-/-)). We found that IL-4 does not play a
      dominant role in the induction of neonatal tolerance as newborn female IL-4(-/-)
      mice could be readily tolerized to the H-Y male Ag. In contrast, mice that lack
      both IL-4 and IL-13 (IL-4(-/-)/IL-13(-/-)) were resistant to the induction of
      neonatal tolerance, and their splenocytes produced exaggerated amounts of IFN
      gamma on rechallenge with the same Ag encountered during the neonatal period.
      These findings argue against the view that IL-4 alone is critical for the
      induction of neonatal tolerance and suggest that the combined actions of both IL
      4 and IL-13 are essential for this process.

PMID- 11441126
TI  - The human ATP-binding cassette (ABC) transporter superfamily.
AB  - The transport of specific molecules across lipid membranes is an essential
      function of all living organisms and a large number of specific transporters have
      evolved to carry out this function. The largest transporter gene family is the
      ATP-binding cassette (ABC) transporter superfamily. These proteins translocate a
      wide variety of substrates including sugars, amino acids, metal ions, peptides,
      and proteins, and a large number of hydrophobic compounds and metabolites across
      extra- and intracellular membranes. ABC genes are essential for many processes in
      the cell, and mutations in these genes cause or contribute to several human
      genetic disorders including cystic fibrosis, neurological disease, retinal
      degeneration, cholesterol and bile transport defects, anemia, and drug response.
      Characterization of eukaryotic genomes has allowed the complete identification of
      all the ABC genes in the yeast Saccharomyces cerevisiae, Drosophila, and C.
      elegans genomes. To date, there are 48 characterized human ABC genes. The genes
      can be divided into seven distinct subfamilies, based on organization of domains
      and amino acid homology. Many ABC genes play a role in the maintenance of the
      lipid bilayer and in the transport of fatty acids and sterols within the body.
      Here, we review the current knowledge of the human ABC genes, their role in
      inherited disease, and understanding of the topology of these genes within the
      membrane.

PMID- 11441127
TI  - A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene
      reveals a stringent requirement of endogenous monounsaturated fatty acids for
      triglyceride synthesis.
AB  - Stearoyl-CoA desaturase (SCD) catalyzes the de novo biosynthesis of oleate and
      palmitoleate, which are the major fatty acids found in triglycerides, cholesteryl
      esters, and phospholipids. A high carbohydrate (lipogenic) diet induces lipogenic
      gene expression by sterol regulatory element binding protein 1 (SREBP-1c)
      mediated gene transcription, leading to an increase in the synthesis of
      triglycerides. The lipogenic diet fed to mice with a null mutation in the SCD1
      gene (SCD-/-) fails to induce the synthesis of triglycerides in liver, despite
      the induction of expression of SREBP-1 and its target genes, fatty acid synthase
      and glycerol-3-phosphate acyltransferase. The lipogenic diet led to a decrease in
      the levels of triglyceride, but an increase in the level of cholesteryl esters of
      saturated fatty acids. Feeding a lipogenic diet supplemented with high levels of
      oleate to the SCD-/- mice resulted in incorporation of oleate in the liver of SCD
      /- mice, but failed to restore triglycerides to the levels in the normal mouse.
      Triglyceride synthesis, as measured by the incorporation of [(3)H]glycerol, was
      dramatically reduced in the liver of SCD-/- mouse fed a lipogenic diet compared
      with the normal mouse. These observations demonstrate that induction of
      triglyceride synthesis is highly dependent on SCD1 gene expression.

PMID- 11441128
TI  - Characterization of enzymes involved in formation of ethyl esters of long-chain
      fatty acids in humans.
AB  - Elevated fatty acid ethyl ester (FAEE) concentrations have been detected in
      postmortem organs from alcoholics and patients acutely intoxicated by alcohol,
      and FAEE have been implicated as mediators of ethanol-induced organ damage. The
      formation of FAEE is catalyzed by acyl-coenzyme A:ethanol O-acyltransferase
      (AEAT) and by FAEE synthase, which utilize acyl-CoA and free fatty acids,
      respectively, as substrates. Because little is known about the capacity of
      various human tissues to synthesize and hydrolyze FAEE, we investigated formation
      of FAEE by AEAT and FAEE synthase in tissue homogenates from human gastric
      ventricular and duodenal mucosa, pancreas, liver, heart, lung, and adipose
      tissue, gallbladder mucosa, and in serum. Liver, duodenal mucosa, and pancreas
      were found to have the highest capacities to synthesize FAEE, mainly due to AEAT.
      FAEE hydrolyzing activity was highest in liver and pancreas, but hardly
      detectable in adipose tissue or heart. Because fatty acids and alcohol are
      absorbed by the intestinal mucosa, intestine may be a major site of FAEE
      synthesis, and FAEE may be delivered via the circulation to other organs and
      taken up by lipoprotein receptor-mediated uptake. A very low rate of FAEE
      hydrolysis was detected in heart and adipose tissue, which probably accounts for
      the previously observed accumulation of FAEE in these organs.

PMID- 11441129
TI  - Characterization of lysosomal acid lipase mutations in the signal peptide and
      mature polypeptide region causing Wolman disease.
AB  - Wolman disease results from an inherited deficiency of lysosomal acid lipase
      (LAL; EC 3.1.1.13). This enzyme is essential for the hydrolysis of cholesteryl
      esters and triacylglycerols derived from endocytosed lipoproteins. Because of a
      complete absence of LAL activity, Wolman patients accumulate progressive amounts
      of cholesteryl esters and triacylglycerols in affected tissues. To investigate
      the nature of the genetic defects causing this disease, mutations in the LAL gene
      from three subjects of Moslem-Arab and Russian descent living in Israel were
      determined. Two homozygotes for a novel 1-bp deletion introducing a premature in
      frame termination codon at amino acid position 106 (S106X) were identified. A
      third subject was a homozygote for a G-5R signal peptide substitution and a G60V
      missense mutation. The functional significance of these mutations was tested by
      in vitro expression of single and double mutants in Spodoptera frugiperda cells.
      Single mutants G60V and S106X and double mutant G-5R/G60V displayed a virtual
      absence of lipase activity in cell extracts and culture medium. Signal peptide
      mutant G-5R retained lipase activity in cell extracts and showed a drastically
      reduced enzyme activity in culture supernatant, indicating that the mutation may
      affect secretion of active enzyme from cells. These results support the notion
      that Wolman disease is a genetically heterogeneous disorder of lipid metabolism.

PMID- 11441130
TI  - Sampling the intramyocellular triglycerides from skeletal muscle.
AB  - To determine the extent and microanatomical distribution of extramyocellular
      adipocytes associated with skeletal muscle, histological, biochemical, nuclear
      magnetic resonance proton spectroscopic and microcomputed tomography techniques
      were employed to analyze skeletal muscle samples from lean and obese Sprague
      Dawley rats. Significant amounts of extramyocellular adipocytes were found on the
      exterior surface of rat gastrocnemius, soleus, and tibialis anterior muscles. The
      triglyceride content of these exterior adipocytes in these muscle groups was 2-
      to 3-fold greater than that of the respective intramyocellular triglyceride pool
      (P = 0.01). Thus, the exterior adipocytes associated with skeletal muscle samples
      are an abundant source of extramyocellular fat potentially contaminating the
      intramyocellular triglyceride pool if not carefully and completely removed. On
      the other hand, no adipocytes were found in the interfascicular space (between
      muscle bundles) or the intrafascicular space (between muscle fibers) in any of
      the three rat muscles. The feasibility of and procedures for removing
      extramyocellular fat by microdissection techniques to obtain pure muscle sample
      were also evaluated. Complete removal of the extramyocellular adipocytes from rat
      skeletal muscle, using microdissection with a stereo microscope, was found to be
      practical and effective. It is concluded that pure muscle samples free of
      contamination by extramyocellular fat can be obtained, but only if
      microdissection techniques are utilized.

PMID- 11441131
TI  - Macrophage-specific expression of class A scavenger receptors enhances granuloma
      formation in the absence of increased lipid deposition.
AB  - Class A scavenger receptors (SR-A) have several proposed functions that could
      impact atherosclerosis and inflammatory processes. To define the function of SR-A
      in vivo, we created C57BL/6 transgenic mice that expressed bovine SR-A under the
      control of the restricted macrophage promoter, lysozyme (lyso-bSR-A). bSR-A mRNA
      was present in cultured peritoneal macrophages of transgenic mice and tissues
      that contain significant macrophages including spleen, lung, and ileum.
      Functional overexpression of SR-A was demonstrated in peritoneal macrophages both
      by augmented cholesterol ester deposition in response to AcLDL and enhanced
      adhesion in transgenic mice compared with nontransgenic littermates. To determine
      whether macrophage-specific expression of bSR-A regulated inflammatory responses,
      granulomas were generated by subcutaneous injection of carrageenan. Granuloma
      size was significantly increased in lyso-bSR-A transgenic mice compared with wild
      type littermates [421 +/- 51 mg (n = 11) vs. 127 +/- 22 mg (n = 10), P < 0.001].
      However, the larger granulomas in lyso-bSR-A transgenic mice were only associated
      with an increase in unesterified cholesterol, and not cholesterol esters.
      Furthermore, granulomas from transgenic mice had an increase in the number of
      macrophages within the tissue.Therefore, macrophage expression of bSR-A increased
      presence of this cell type in granulomas without enhancing the deposition of
      cholesterol esters, consistent with a role of the adhesive property of the
      protein.

PMID- 11441132
TI  - Distribution of conjugated linoleic acid and metabolites in different lipid
      fractions in the rat liver.
AB  - Conjugated linoleic acid (CLA) is known to provide certain health benefits in
      experimental animal models. The major CLA isomer in food is c 9,t11-CLA. A
      primary objective of this study was to investigate the uptake of c 9,t11-CLA and
      its downstream metabolites into various lipid fractions in the liver of rats fed
      either a high or low CLA diet (containing 0.1 or 0.8 g CLA/100 g diet,
      respectively). As expected, the levels of all conjugated diene (CD) fatty acids
      (CD 18:2 + CD 18:3 + CD 20:3 + CD 20:4) were elevated about 8-fold in the high
      CLA diet group. However, there was no change in the distribution of CLA and CLA
      metabolites into various lipid fractions due to CLA intake. Unlike linoleic acid
      or gamma-linolenic acid, which were distributed mainly in phospholipids, CD 18:2,
      CD 18:3, and CD 20:3 were incorporated primarily in neutral lipid. Furthermore,
      the incorporation of all nonconjugated unsaturated fatty acids was not perturbed
      by CLA. Regardless of the level of CLA in the diet, CD 20:4 was predominantly
      enriched in phosphatidylserine and phosphatidylinositol. In contrast, arachidonic
      acid was primarily enriched in phosphatidylcholine and less so in
      phosphatidylethanolamine. The above findings may have potential implication
      regarding the role of CLA in modulating eicosanoid metabolism.

PMID- 11441133
TI  - Golgi localization and phosphorylation of oxysterol binding protein in Niemann
      Pick C and U18666A-treated cells.
AB  - Oxysterol binding protein (OSBP) translocation between Golgi and
      vesicular/cytoplasmic compartments is affected by conditions that alter
      cholesterol and sphingomyelin homeostasis, indicating a role in lipid and sterol
      regulation in this organelle. In this study, we show that OSBP dissociation from
      the Golgi apparatus was inhibited when LDL cholesterol efflux from lysosomes was
      blocked in Niemann-Pick C (NPC) or U18666A [3-beta-[2
      (diethylamino)ethoxy]androst-5-en-17-one]-treated fibroblasts. Dissociation of
      OSBP from the Golgi apparatus in response to LDL was independent of de novo
      cholesterol biosynthesis. OSBP did not localize with filipin-stained lysosomal
      cholesterol, and the NPC defect did not alter OSBP expression or phosphorylation.
      However, OSBP in the Golgi apparatus was progressively dephosphorylated (as
      assessed by a molecular mass shift on SDS-PAGE) in U18666A-treated fibroblasts or
      Chinese hamster ovary cells as a result of combined inhibition of LDL cholesterol
      transport and de novo cholesterol synthesis. In vivo phosphopeptide mapping and
      mutagenesis of OSBP was used to identify the cholesterol-sensitive
      phosphorylation sites at serines 381, 384, and 387 that were responsible for the
      altered mobility on SDS-PAGE. NPC-1 protein-mediated release of LDL-derived
      cholesterol and de novo biosynthesis regulates OSBP localization and
      phosphorylation. This indicates that OSBP responds to or senses altered cellular
      sterol content and transport.

PMID- 11441134
TI  - Novel compound heterozygous mutations for lipoprotein lipase deficiency. A G-to-T
      transversion at the first position of exon 5 causing G154V missense mutation and
      a 5' splice site mutation of intron 8.
AB  - We systematically investigated the molecular defects causing a primary LPL
      deficiency in a Japanese male infant (patient DI) with fasting
      hyperchylomicronemia (type I hyperlipoproteinemia) and in his parents. Patient DI
      had neither LPL activity nor immunoreactive LPL mass in the pre- and post-heparin
      plasma. The patient was a compound heterozygote for novel mutations consisting of
      a G-to-T transversion at the first nucleotide of exon 5 [+1 position of 3'
      acceptor splice site (3'-ass) of intron 4] and a T-to-C transition in the
      invariant GT at position +2 of the 5' donor splice site (5'-dss) of intron 8
      (Int8/5'-dss/t(+2)c). The G-to-T transversion, although affecting the 11
      nucleotide of the 3'-consensus acceptor splice site, resulted in a substitution
      of Gly(154) to Val (G154V; GG(716)C(-->)GTC). The mutant G154V LPL expressed in
      COS-1 cells was catalytically inactive and hardly released from the cells by
      heparin. The Int8/5'-dss/t(+2)c mutation inactivated the authentic 5' splice site
      of intron 8 and led to the utilization of a cryptic 5'-dss in exon 8 as an
      alternative splice site 133 basepairs upstream from the authentic splice site,
      thereby causing joining of a part of exon 8 to exon 9 with skipping of a 134-bp
      fragment of exon 8 and intron 8. These additional mutations in the consensus
      sequences of the 3' and 5' splice sites might be useful for better understanding
      the factors that are involved in splice site selection in vivo.

PMID- 11441135
TI  - Oxidation of LDL by rabbit and human 15-lipoxygenase: prevalence of nonenzymatic
      reactions.
AB  - 15-Lipoxygenase (15-LO)-induced oxidation of lipids in human LDL may be pro
      atherogenic. However, the extent to which 15-LO promotes enzymatic oxidation of
      esterified (i.e., major) lipids in LDL may depend on various factors. Here, we
      show that overall, LDL lipid oxidation was favored with high activity of human 15
      LO, that phospholipids were the preferred esterified substrate, and that low
      temperature maintained a higher proportion of enzymatic product. However, under
      all conditions, 15-LO induced alpha-tocopherol consumption and the accumulation
      of nonenzymatic products that predominated with increasing time of incubation and
      inactivation of the enzyme. Lysates prepared from cells overexpressing human 15
      LO oxidized linoleic acid readily and in an almost exclusive enzymatic manner. In
      sharp contrast, such lysates failed to oxidize LDL lipids unless linoleic acid
      was added, in which case nonenzymatic oxidation of LDL lipids occurred. We
      conclude that although purified 15-LO can oxidize isolated LDL lipids in vitro,
      such oxygenation always includes nonenzymatic reactions that likely play a major
      role in the more extensive oxidation of LDL by cell-derived 15-LO.

PMID- 11441136
TI  - Neutral sterols of rat epididymis. High concentrations of dehydrocholesterols in
      rat caput epididymidis.
AB  - Phospholipids and sterols are known to have multiple functions in reproductive
      tissue of mammals. High concentrations of the cholesterol precursor desmosterol
      have been described in testis, epididymis, and spermatozoa of various species.
      These findings and the recent discovery of some cholesterol precursors as meiosis
      activating sterols suggest important functions of cholesterol precursors in
      fertility. Many sterol intermediates appear from the 19-step conversion of
      lanosterol, the first sterol synthesized in the cascade of cholesterol synthesis,
      to cholesterol. The biochemical basis of the genetically inherited Smith-Lemli
      Opitz syndrome has been described as a defective conversion of 7
      dehydrocholesterol to cholesterol. Since this discovery, interest has focused on
      this special cholesterol precursor. Here, we report high concentrations of 7- and
      8-dehydrocholesterol in caput epididymidis and spermatozoa derived from caput
      epididymidis of Sprague-Dawley and Wistar rats, which comprised up to 30% of
      total sterols. In contrast to caput epididymidis, 7- and 8-dehydrocholesterol
      were barely detected in cauda epididymidis or testis. Desmosterol increased
      several times from caput to cauda epididymidis. This is the first report of the
      natural appearance of high concentrations of dehydrocholesterols in mammalian
      tissue, and it underlines the putative importance of cholesterol precursors in
      reproductive tissue.

PMID- 11441137
TI  - Effects of increasing hydrophobicity on the physical-chemical and biological
      properties of a class A amphipathic helical peptide.
AB  - We have recently shown that a class A amphipathic peptide 5F with increased
      amphipathicity protected mice from diet-induced atherosclerosis (Garber et al. J.
      Lipid Res. 2001. 42: 545-552). We have now examined the effects of increasing the
      hydrophobicity of a series of homologous class A amphipathic peptides, including
      5F, on physical and functional properties related to atherosclerosis inhibition
      by systematically replacing existing nonpolar amino acids with phenylalanine. The
      peptides, based on the sequence Ac-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-NH(2) (Ac
      18A-NH(2) or 2F) were: 3F(3)(Ac-F(3)18A-NH(2)), 3F(14)(Ac-F(14)18A-NH(2)), 4F(Ac
      F(3,14)18A-NH(2)), 5F(Ac-F(11,14,17) 18A-NH(2)), 6F(Ac-F(10,11,14,17)18A-NH(2)),
      and 7F(Ac-F(3,10,11,14,17) 18A-NH(2)). Measurements of aqueous solubility, HPLC
      retention time, exclusion pressure for penetration into an egg
      phosphatidylcholine (EPC) monolayer, and rates of EPC solubilization revealed an
      abrupt increase in the hydrophobicity between peptides 4F and 5F; this was
      accompanied by increased ability to associate with phospholipids. The peptides 6F
      and 7F were less effective, indicating a limit to increased hydrophobicity for
      promoting lipid interaction in these peptides. Despite this marked increase in
      lipid affinity, these peptides were less effective than apoA-I in activating the
      plasma enzyme, lecithin:cholesterol acyltransferase, with 5F activating LCAT the
      best (80% of apoA-I). Peptides 4F, 5F, and 6F were equally potent in inhibiting
      LDL-induced monocyte chemotactic activity. These studies suggest that an
      appropriate balance between peptide-peptide and peptide-lipid interactions is
      required for optimal biological activity of amphipathic peptides. These studies
      provide a rationale for the design of small apoA-I-mimetics with increased
      potency for atherosclerosis inhibition.

PMID- 11441138
TI  - The omega-hydroxyceramides of pig epidermis are attached to corneocytes solely
      through omega-hydroxyl groups.
AB  - The cornified outer cells of mammalian epidermis possess a monolayer of omega
      hydroxyceramides that are ester-linked to the exterior of a cross-linked protein
      envelope. In the present study, conclusive evidence was sought on which of the
      ceramide hydroxyl groups are involved in the linkage to protein. This was
      obtained by derivatizing all free hydroxyl groups in isolated solvent-extracted
      porcine stratum corneum using triisopropylsilyl (TIPS) chloride in pyridine in
      the presence of silver nitrate. After an 18-h reaction, the tissue was recovered,
      rinsed, and the derivatized ceramides were then released from protein linkage by
      hydrolysis with 1M KOH in 95% methanol. This gave a single ceramide product that
      was shown by nuclear magnetic resonance to contain two triisopropyl groups.
      Acetylation of the product using acetic anhydride in pyridine resulted in a
      downfield shift of the NMR signal for the omega-methylene protons, showing that
      it was the omega-hydroxyl that was free in the initial reaction product, and
      subsequently was acetylated. These results show that all of the omega
      hydroxyceramides of corneocyte lipid envelopes are attached to protein through
      their omega-hydroxyl groups.

PMID- 11441139
TI  - Effect of maternal hypercholesterolemia on fetal sterol metabolism in the Golden
      Syrian hamster.
AB  - The fetus obtains a significant amount of cholesterol from de novo synthesis.
      Studies have suggested that maternal cholesterol may also contribute to the
      cholesterol accrued in the fetus. Thus, the present studies were completed to
      determine whether diet-induced maternal hypercholesterolemia would affect fetal
      sterol metabolism. To accomplish this, maternal plasma cholesterol concentrations
      were increased sequentially by feeding hamsters 0.0%, 0.12%, 0.5%, and 2.0%
      cholesterol. At 11 days into a gestational period of 15.5 days, cholesterol
      concentrations and sterol synthesis rates were measured in the three fetal
      tissues: the placenta, yolk sac, and fetus. In the placenta and yolk sac, the
      cholesterol concentration increased significantly when dams were fed as little as
      0.12% cholesterol (P < 0.0167), and sterol synthesis rates decreased in dams fed
      at least 0.5% or 2% cholesterol, respectively (P < 0.0167). In the fetus, changes
      in fetal cholesterol concentration and sterol synthesis rates occurred only when
      dams were fed at least 0.5% cholesterol, which corresponded to a greater than 2
      fold increase in maternal plasma cholesterol concentrations. When the cholesterol
      concentration in the fetal tissues in each animal was plotted as a function of
      maternal plasma cholesterol concentration, a linear relationship was found (P <
      0.001). These studies demonstrate that sterol homeostasis in fetal tissues,
      including the fetus, is affected by maternal plasma cholesterol concentration in
      a gradient fashion and that sterol metabolism in the fetus is dependent on sterol
      homeostasis in the yolk sac and/or placenta.

PMID- 11441140
TI  - Corn oil-induced decrease in arterial thrombosis tendency may be related to
      altered plasma vitamin K transport.
AB  - In this article we report the effects of low and high fat diets on the arterial
      thrombosis tendency in rats. The animal system used was the aorta loop model, in
      which we compared the effect of saturated (hardened coconut oil, HCO) and
      unsaturated (sunflower seed oil, SSO; corn oil, CO) fatty acids on the arterial
      thrombosis tendency at high fat intake (50 energy%, 45 energy% of which was
      either HCO, SSO, or CO). Under these conditions both SSO and CO had a beneficial
      effect (relative to HCO) on the arterial thrombosis tendency. In a subsequent
      study we compared these high fat diets with a low fat diet (5 energy%). As
      compared with the low fat diet, only CO significantly decreased the thrombosis
      risk. Serum vitamin K and triglycerides had decreased substantially after the CO
      diet, and to a much lesser extent after the SSO diet. It is concluded that corn
      oil may have a mildly anticoagulant effect, the potential benefit of which is
      discussed.

PMID- 11441141
TI  - Interaction with proteoglycans enhances the sterol efflux produced by endogenous
      expression of macrophage apoE.
AB  - Endogenous expression of apolipoprotein (apo)E in macrophages facilitates
      cholesterol efflux in the presence and absence of extracellular sterol acceptors.
      A proteoglycan-associated pool of apoE has also been described. The relationship
      between a proteoglycan-associated pool of apoE and enhanced cholesterol efflux
      was investigated in these studies. Inhibition of proteoglycan expression reduced
      cholesterol efflux from apoE-expressing cells ( J774E(+)) in the presence and
      absence of HDL, but did not do so from nonexpressing cells ( J774E(-)). The
      effect of proteoglycan depletion on sterol efflux from J774E(+) cells was
      confirmed by measuring differences in cell sterol mass, secreted sterol mass, and
      sterol efflux rates. Furthermore, apoE-containing particles secreted from
      proteoglycan-depleted J774E(+) cells were denser than those secreted from
      J774E(+) cells with intact proteoglycan expression. Also, in J774E(+) cells with
      intact proteoglycans, apoE particles isolated from the cell surface proteoglycan
      layer were denser than secreted particles. The apoE-lipid particles isolated from
      the cell surface proteoglycan layer had a lower lipid-to-apoE and cholesterol-to
      apoE ratio compared with secreted particles. In distinction, proteoglycan
      depletion of J774E(-) cells did not reduce sterol efflux produced by the
      exogenous addition of apoE. These observations indicate that one mechanism by
      which endogenous expression of apoE facilitates effective cholesterol efflux from
      macrophages is related to its retention at the cell surface in a proteoglycan
      associated pool. Further, our data suggest that apoE arrives at the cell surface
      in a relatively lipid-poor state, and that a proximate source of lipid available
      to the proteoglycan-bound apoE at the cell surface resides in the plasma
      membrane.

PMID- 11441142
TI  - Molecular characterization of L-CPT I deficiency in six patients: insights into
      function of the native enzyme.
AB  - Carnitine palmitoyltransferase I (CPT I) catalyzes the formation of
      acylcarnitine, the first step in the oxidation of long-chain fatty acids in
      mitochondria. The enzyme exists as liver (L-CPT I) and muscle (M-CPT I) isoforms
      that are encoded by separate genes. Genetic deficiency of L-CPT I, which has been
      reported in 16 patients from 13 families, is characterized by episodes of
      hypoketotic hypoglycemia beginning in early childhood and is usually associated
      with fasting or illness. To date, only two mutations associated with L-CPT I
      deficiency have been reported. In the present study we have identified and
      characterized the mutations underlying L-CPT I deficiency in six patients: five
      with classic symptoms of L-CPT I deficiency and one with symptoms that have not
      previously been associated with this disorder (muscle cramps and pain).
      Transfection of the mutant L-CPT I cDNAs in COS cells resulted in L-CPT I mRNA
      levels that were comparable to those expressed from the wild-type construct.
      Western blotting revealed lower levels of each of the mutant proteins, indicating
      that the low enzyme activity associated with these mutations was due, at least in
      part, to protein instability. The patient with atypical symptoms had
      approximately 20% of normal L-CPT I activity and was homozygous for a mutation
      (c.1436C-->T) that substituted leucine for proline at codon 479. Assays performed
      with his cultured skin fibroblasts indicated that this mutation confers partial
      resistance to the inhibitory effects of malonyl-CoA. The demonstration of L-CPT I
      deficiency in this patient suggests that the spectrum of clinical sequelae
      associated with loss or alteration of L-CPT I function may be broader than was
      previously recognized.

PMID- 11441143
TI  - Characterization of four lipoprotein classes in human cerebrospinal fluid.
AB  - Lipoprotein metabolism in brain has not yet been fully elucidated, although there
      are a few reports concerning lipids in the brain and lipoproteins and
      apolipoproteins in the cerebrospinal fluid (CSF). To establish normal levels of
      lipoproteins in human CSF, total cholesterol, phospholipids, and fatty acids as
      well as apolipoprotein E (apoE) and apoA-I levels were determined in CSF samples
      from 216 individuals. For particle characterization, lipoproteins from human CSF
      were isolated by affinity chromatography and analyzed for size, lipid and
      apolipoprotein composition. Two consecutive immunoaffinity columns with
      antibodies, first against apoE and subsequently against apoA-I, were used to
      define four distinct lipoprotein classes. The major lipoprotein fraction
      consisted of particles of 13;-20 nm containing apoE and apoA-I as well as apoA
      IV, apoD, apoH, and apoJ. In the second particle class (13;-18 nm) mainly apoA-I
      and apoA-II but no apoE was detected. Third, there was a small number of large
      particles (18;-22 nm) containing no apoA-I but apoE associated with apoA-IV,
      apoD, and apoJ. In the unbound fraction we detected small particles (10;-12 nm)
      with low lipid content containing apoA-IV, apoD, apoH, and apoJ. In summary, we
      established lipid and apolipoprotein levels in CSF in a large group of
      individuals and described four distinct lipoprotein classes in human CSF,
      differing in their apolipoprotein pattern, lipid composition, and size. On the
      basis of our own data and previous findings from other groups, we propose a
      classification of CSF lipoproteins.

PMID- 11441144
TI  - Age-related changes in cholesterol metabolism in macrosomic offspring of rats
      with streptozotocin-induced diabetes.
AB  - The aim of this study was to determine the impact of diabetic macrosomia on
      cholesterol and lipoprotein metabolism. Age-related changes in the activities of
      serum LCAT, hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT,
      the major enzymes involved in cholesterol metabolism, were determined in
      macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and
      lipoprotein cholesterol contents were also examined. Mild hyperglycemia in
      pregnant rats was induced by intraperitoneal injection of streptozotocin (40
      mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected
      with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL(1), and
      HDL(2-3) cholesterol levels (P < 0.05) associated with increased LCAT activity
      (+57%) compared with control values. At 1 and 2 months of life, serum and
      lipoprotein cholesterol concentrations in macrosomic rats were similar to those
      of controls, whereas LCAT activity remained elevated about 1.5-fold. In addition,
      there was no change in hepatic cholesterol contents but hepatic HMG-CoA
      reductase, cholesterol 7alpha-hydroxylase, and ACAT activities were higher in
      both macrosomic males and females than in their respective controls (P < 0.01).
      By 3 months, macrosomic rats had developed hypercholesterolemia with a rise in
      all lipoproteins. Enzyme activities were still increased in these mature
      macrosomic rats, and hepatic cholesteryl esters were higher only in macrosomic
      females. These data demonstrate an overproduction, combined with overutilization,
      of cholesterol during the phase of rapid growth in macrosomic rats. However,
      cholesterol oversynthesis exceeded its removal and was a major contributor to
      hypercholesterolemia in adult macrosomic rats. In conclusion, macrosomia was
      associated with alterations in cholesterol metabolism through adulthood.

PMID- 11441145
TI  - Effects of docosahexaenoic acid on annular lipid fluidity of the rat bile
      canalicular plasma membrane.
AB  - The role of docosahexaenoic acid (DHA) in the fluidity of the annular lipid
      regions and their associated membrane-bound proteins is still not as well
      understood as that in the global (bulk) lipid regions. We therefore studied the
      effects of dietary DHA on the relationship between annular and global lipid
      fluidity and membrane-bound enzymes such as 5'-nucleotidase and Mg(2)+-ATPase in
      the rat bile canalicular membrane. Dietary DHA caused significant increases in 5'
      nucleotidase and Mg(2)+-ATPase activity and in global and annular lipid fluidity,
      a higher increase in fluidity in the annular lipids than the global lipids, and a
      decrease in the cholesterol-to-phospholipid molar ratio in the canalicular
      membrane. Plasma total cholesterol and LDL cholesterol decreased, and fecal
      cholesterol increased in the DHA-fed rats. No changes were observed in oxidative
      markers, but glutathione peroxidase increased in the liver with DHA feeding.
      Annular lipid fluidity, but not global lipid fluidity, correlated remarkably well
      with DHA, synchronously with the activities of 5'-nucleotidase and Mg(2)+-ATPase.
      The data indicate that the DHA-induced increase in annular lipid fluidity is
      responsible for the increases observed in the enzyme activity. We therefore
      concluded that the increased activity of membrane-bound enzymes and transporters
      induced by DHA and the concomitant increase in annular lipid fluidity comprise
      one of the mechanisms involved in DHA-induced clearance of plasma cholesterol.

PMID- 11441146
TI  - Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors.
AB  - Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control
      gene expression as a function of the light-dark cycle. Although built to
      fluctuate at or near a 24-hour cycle, the clock can be entrained by light,
      activity, or food. Here we show that the DNA-binding activity of the Clock:BMAL1
      and NPAS2:BMAL1 heterodimers is regulated by the redox state of nicotinamide
      adenine dinucleotide (NAD) cofactors in a purified system. The reduced forms of
      the redox cofactors, NAD(H) and NADP(H), strongly enhance DNA binding of the
      Clock:BMAL1 and NPAS2:BMAL1 heterodimers, whereas the oxidized forms inhibit.
      These observations raise the possibility that food, neuronal activity, or both
      may entrain the circadian clock by direct modulation of cellular redox state.

PMID- 11441148
TI  - Observation of chaos-assisted tunneling between islands of stability.
AB  - We report the direct observation of quantum dynamical tunneling of atoms between
      separated momentum regions in phase space. We study how the tunneling
      oscillations are affected as a quantum symmetry is broken and as the initial
      atomic state is changed. We also provide evidence that the tunneling rate is
      greatly enhanced by the presence of chaos in the classical dynamics. This
      tunneling phenomenon represents a dramatic manifestation of underlying classical
      chaos in a quantum system.

PMID- 11441147
TI  - NPAS2: an analog of clock operative in the mammalian forebrain.
AB  - Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed
      primarily in the mammalian forebrain. NPAS2 is highly related in primary amino
      acid sequence to Clock, a transcription factor expressed in the suprachiasmatic
      nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To
      investigate the biological role of NPAS2, we prepared a neuroblastoma cell line
      capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified
      putative target genes by representational difference analysis, DNA microarrays,
      and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of
      the endogenous Per1, Per2, and Cry1 genes, which encode negatively activating
      components of the circadian regulatory apparatus, and repressed transcription of
      the endogenous BMAL1 gene. Analysis of the frontal cortex of wild-type mice kept
      in a 24-hour light-dark cycle revealed that Per1, Per2, and Cry1 mRNA levels were
      elevated during darkness and reduced during light, whereas BMAL1 mRNA displayed
      the opposite pattern. In situ hybridization assays of mice kept in constant
      darkness revealed that Per2 mRNA abundance did not oscillate as a function of the
      circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of
      a molecular clock operative in the mammalian forebrain.

PMID- 11441149
TI  - Quantum physics. No mere anarchy.

PMID- 11441151
TI  - Iraq's cultural heritage: collateral damage.

PMID- 11441150
TI  - Circadian rhythms. Chronobiology--reducing time.

PMID- 11441152
TI  - Virology. Old guard urges virologists to go back to basics.

PMID- 11441153
TI  - Wetlands restoration. Recreated wetlands no match for original.

PMID- 11441154
TI  - Kennewick man. Missing thighbones suddenly reappear.

PMID- 11441155
TI  - Neuroscience. Neurons fix memories in the mind's eye.

PMID- 11441156
TI  - Neuroscience. Elusive protein auditions for several new roles.

PMID- 11441157
TI  - Marine biology. Interest blooms in growing jellyfish boom.

PMID- 11441158
TI  - Marine mammals. By a whisker, harbor seals catch their prey.

PMID- 11441160
TI  - Invisible crisis. Destruction in Mesopotamia.

PMID- 11441159
TI  - Climate change. Experts urge speedup to mine 'archives'.

PMID- 11441162
TI  - Foreigners return. Iraq opening sets off scramble for sites.

PMID- 11441163
TI  - Foreigners return. Sale of Nineveh fragments exposes looting network.

PMID- 11441164
TI  - Digging in. New digs draw applause and concern.

PMID- 11441165
TI  - Digging in. Rifle-toting researcher fights to protect ancient sites.

PMID- 11441166
TI  - Queens' gold. Banished Assyrian gold to reemerge from vault.

PMID- 11441167
TI  - Essays on science and society. Artistic creativity and the brain.

PMID- 11441168
TI  - Planetary science. News from the edge of interstellar space.

PMID- 11441169
TI  - Marine biology. Expansion of the marine Archaea.

PMID- 11441170
TI  - Drug delivery. Drugs on target.

PMID- 11441171
TI  - Development. The message is in the translation.

PMID- 11441172
TI  - Signal transduction. Bringing channels closer to the action!

PMID- 11441173
TI  - The early evolution of the inner solar system: a meteoritic perspective.
AB  - Formation of the solar system may have been triggered by a stellar wind. From
      then on, the solar system would have followed a conventional evolutionary path,
      including the formation of a disk and bipolar jets. The now extinct short-lived
      radionuclides beryllium-10 and, possibly, manganese-53 that were present in
      meteorites probably resulted from energetic particle irradiation within the solar
      system. Calcium-aluminum-rich inclusions (the oldest known solar system solids)
      and chondrules could have been produced by the bipolar jets, but it is more
      likely that they formed during localized events in the asteroid belt. The
      chondritic meteorites formed within the temperature range (100 to 400 kelvin)
      inferred for the midplane of classical T Tauri disks at 2 to 3 astronomical units
      from their central stars. However, these meteorites may retain a chemical memory
      of earlier times when midplane temperatures were much higher. Dissipation of the
      solar nebula occurred within a few million years of solar system formation,
      whereas differentiation of asteroidal-sized bodies occurred within 5 to 15
      million years. The terrestrial planets took approximately 100 million years to
      form. Consequently, they would have accreted already differentiated bodies, and
      their final assembly was not completed until after the solar nebula had
      dispersed. This implies that water-bearing asteroids and/or icy planetesimals
      that formed near Jupiter are the likely sources of Earth's water.

PMID- 11441174
TI  - Collapse of the California Current during glacial maxima linked to climate change
      on land.
AB  - Time series of alkenone unsaturation indices gathered along the California margin
      reveal large (4 degrees to 8 degrees C) glacial-interglacial changes in sea
      surface temperature (SST) over the past 550,000 years. Interglacial times with
      SSTs equal to or exceeding that of the Holocene contain peak abundances in the
      pollen of redwood, the distinctive component of the temperate rainforest of the
      northwest coast of California. In the region now dominated by the California
      Current, SSTs warmed 10,000 to 15,000 years in advance of deglaciation at each of
      the past five glacial maxima. SSTs did not rise in advance of deglaciation south
      of the modern California Current front. Glacial warming along the California
      margin therefore is a regional signal of the weakening of the California Current
      during times when large ice sheets reorganized wind systems over the North
      Pacific. Both the timing and magnitude of the SST estimates suggest that the
      Devils Hole (Nevada) calcite record represents regional but not global
      paleotemperatures, and hence does not pose a fundamental challenge to the orbital
      ("Milankovitch") theory of the Ice Ages.

PMID- 11441175
TI  - Carbon nanotube single-electron transistors at room temperature.
AB  - Room-temperature single-electron transistors are realized within individual
      metallic single-wall carbon nanotube molecules. The devices feature a short (down
      to approximately 20 nanometers) nanotube section that is created by inducing
      local barriers into the tube with an atomic force microscope. Coulomb charging is
      observed at room temperature, with an addition energy of 120 millielectron volts,
      which substantially exceeds the thermal energy. At low temperatures, we resolve
      the quantum energy levels corresponding to the small island. We observe
      unconventional power-law dependencies in the measured transport properties for
      which we suggest a resonant tunneling Luttinger-liquid mechanism.

PMID- 11441176
TI  - Fully conjugated porphyrin tapes with electronic absorption bands that reach into
      infrared.
AB  - Scandium(III)-catalyzed oxidation of meso-meso-linked zinc(II)-porphyrin arrays
      (up to dodecamers) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) led to
      efficient formation of triply meso-meso-, beta-beta-, and beta-beta-linked
      zinc(II)-oligoiporphyrins with 62 to 91% yields. These fused tape-shaped
      porphyrin arrays display extremely red-shifted absorption bands that reflect
      extensively pi-conjugated electronic systems and a low excitation gap. The lowest
      electronic absorption bands become increasingly intensified and red-shifted upon
      the increase in the number of porphyrins and eventually reach a peak electronic
      excitation for the dodecamer at approximately 3500 wavenumber. The one-electron
      oxidation potentials also decreased progressively upon the increase in the number
      of porphyrins. These properties in long and rigid molecular shapes suggest their
      potential use as molecular wires.

PMID- 11441177
TI  - Approach to high-resolution ex situ NMR spectroscopy.
AB  - Nuclear magnetic resonance (NMR) experiments are typically performed with samples
      immersed in a magnet shimmed to high homogeneity. However, there are many
      circumstances in which it is impractical or undesirable to insert objects or
      subjects into the bore of a high-field magnet. Here we present a methodology
      based on an adaptation of nutation echoes that provides resolved spectra in the
      presence of matched inhomogeneous static and radiofrequency fields, thereby
      opening the way to high-resolution ex situ NMR. The observation of chemical
      shifts is regained through the use of multiple-pulse sequences of correlated,
      composite z-rotation pulses, producing resolved NMR spectra of liquid samples.

PMID- 11441178
TI  - Regional climate impacts of the Northern Hemisphere annular mode.
AB  - The Northern Hemisphere annular mode (NAM) (also known as the North Atlantic
      Oscillation) is shown to exert a strong influence on wintertime climate, not only
      over the Euro-Atlantic half of the hemisphere as documented in previous studies,
      but over the Pacific half as well. It affects not only the mean conditions, but
      also the day-to-day variability, modulating the intensity of mid-latitude storms
      and the frequency of occurrence of high-latitude blocking and cold air outbreaks
      throughout the hemisphere. The recent trend in the NAM toward its high-index
      polarity with stronger subpolar westerlies has tended to reduce the severity of
      winter weather over most middle- and high-latitude Northern Hemisphere
      continental regions.

PMID- 11441179
TI  - Seasonal modulation of interseismic strain buildup in northeastern Japan driven
      by snow loads.
AB  - Distinct periodic variations with annual frequencies are often found in the time
      series of continuous Global Positioning System (GPS) site coordinates in
      northeastern Japan. They show maximum arc-normal contraction of a few millimeters
      as well as maximum subsidence of 1 to 2 centimeters, both in March. In
      northeastern Japan, it snows heavily on the western flank of the backbone range,
      attaining a maximum depth of several meters in March. When observed snow depths
      were compared with the load distribution estimated from the GPS data, the surface
      loads caused by the snow were found to be largely responsible for the annual
      displacement of GPS sites. The snow load modulates secular strain buildup in
      northeastern Japan due to the Pacific Plate subduction, but its relevance to the
      seasonal change of earthquake occurrences remains uncertain.

PMID- 11441180
TI  - Massive expansion of marine archaea during a mid-Cretaceous oceanic anoxic event.
AB  - Biogeochemical and stable carbon isotopic analysis of black-shale sequences
      deposited during an Albian oceanic anoxic event (approximately 112 million years
      ago) indicate that up to 80 weight percent of sedimentary organic carbon is
      derived from marine, nonthermophilic archaea. The carbon-13 content of archaeal
      molecular fossils indicates that these archaea were living chemoautotrophically.
      Their massive expansion may have been a response to the strong stratification of
      the ocean during this anoxic event. Indeed, the sedimentary record of archaeal
      membrane lipids suggests that this anoxic event marks a time in Earth history at
      which certain hyperthermophilic archaea adapted to low-temperature environments.

PMID- 11441181
TI  - Epigenetic instability in ES cells and cloned mice.
AB  - Cloning by nuclear transfer (NT) is an inefficient process in which most clones
      die before birth and survivors often display growth abnormalities. In an effort
      to correlate gene expression with survival and fetal overgrowth, we have examined
      imprinted gene expression in both mice cloned by nuclear transfer and in the
      embryonic stem (ES) cell donor populations from which they were derived. The
      epigenetic state of the ES cell genome was found to be extremely unstable.
      Similarly, variation in imprinted gene expression was observed in most cloned
      mice, even in those derived from ES cells of the same subclone. Many of the
      animals survived to adulthood despite widespread gene dysregulation, indicating
      that mammalian development may be rather tolerant to epigenetic aberrations of
      the genome. These data imply that even apparently normal cloned animals may have
      subtle abnormalities in gene expression.

PMID- 11441182
TI  - A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel
      Cav1.2.
AB  - The existence of a large number of receptors coupled to heterotrimeric guanine
      nucleotide binding proteins (G proteins) raises the question of how a particular
      receptor selectively regulates specific targets. We provide insight into this
      question by identifying a prototypical macromolecular signaling complex. The
      beta(2) adrenergic receptor was found to be directly associated with one of its
      ultimate effectors, the class C L-type calcium channel Ca(v)1.2. This complex
      also contained a G protein, an adenylyl cyclase, cyclic adenosine monophosphate
      dependent protein kinase, and the counterbalancing phosphatase PP2A. Our
      electrophysiological recordings from hippocampal neurons demonstrate highly
      localized signal transduction from the receptor to the channel. The assembly of
      this signaling complex provides a mechanism that ensures specific and rapid
      signaling by a G protein-coupled receptor.

PMID- 11441183
TI  - Hydrodynamic trail-following in harbor seals (Phoca vitulina).
AB  - Marine mammals often forage in dark or turbid waters. Whereas dolphins use
      echolocation under such conditions, pinnipeds apparently lack this sensory
      ability. For seals hunting in the dark, one source of sensory information may
      consist of fish-generated water movements, which seals can detect with their
      highly sensitive whiskers. Water movements in the wake of fishes persist for
      several minutes. Here we show that blindfolded seals can use their whiskers to
      detect and accurately follow hydrodynamic trails generated by a miniature
      submarine. This shows that hydrodynamic information can be used for long-distance
      prey location.

PMID- 11441184
TI  - Human chromosome 19 and related regions in mouse: conservative and lineage
      specific evolution.
AB  - To illuminate the function and evolutionary history of both genomes, we sequenced
      mouse DNA related to human chromosome 19. Comparative sequence alignments yielded
      confirmatory evidence for hypothetical genes and identified exons, regulatory
      elements, and candidate genes that were missed by other predictive methods.
      Chromosome-wide comparisons revealed a difference between single-copy HSA19
      genes, which are overwhelmingly conserved in mouse, and genes residing in tandem
      familial clusters, which differ extensively in number, coding capacity, and
      organization between the two species. Finally, we sequenced breakpoints of all 15
      evolutionary rearrangements, providing a view of the forces that drive chromosome
      evolution in mammals.

PMID- 11441185
TI  - Ventroptin: a BMP-4 antagonist expressed in a double-gradient pattern in the
      retina.
AB  - In the visual system, the establishment of the anteroposterior and dorsoventral
      axes in the retina and tectum during development is important for topographic
      retinotectal projection. We identified chick Ventroptin, an antagonist of bone
      morphogenetic protein 4 (BMP-4), which is mainly expressed in the ventral retina,
      not only with a ventral high-dorsal low gradient but also with a nasal high
      temporal low gradient at later stages. Misexpression of Ventroptin altered
      expression patterns of several topographic genes in the retina and projection of
      the retinal axons to the tectum along both axes. Thus, the topographic
      retinotectal projection appears to be specified by the double-gradient molecule
      Ventroptin along the two axes.

PMID- 11441186
TI  - A transcriptionally [correction of transcriptively] active complex of APP with
      Fe65 and histone acetyltransferase Tip60.
AB  - Amyloid-beta precursor protein (APP), a widely expressed cell-surface protein, is
      cleaved in the transmembrane region by gamma-secretase. gamma-Cleavage of APP
      produces the extracellular amyloid beta-peptide of Alzheimer's disease and
      releases an intracellular tail fragment of unknown physiological function. We now
      demonstrate that the cytoplasmic tail of APP forms a multimeric complex with the
      nuclear adaptor protein Fe65 and the histone acetyltransferase Tip60. This
      complex potently stimulates transcription via heterologous Gal4- or LexA-DNA
      binding domains, suggesting that release of the cytoplasmic tail of APP by gamma
      cleavage may function in gene expression.

PMID- 11441187
TI  - A neural correlate of working memory in the monkey primary visual cortex.
AB  - The brain frequently needs to store information for short periods. In vision,
      this means that the perceptual correlate of a stimulus has to be maintained
      temporally once the stimulus has been removed from the visual scene. However, it
      is not known how the visual system transfers sensory information into a memory
      component. Here, we identify a neural correlate of working memory in the monkey
      primary visual cortex (V1). We propose that this component may link sensory
      activity with memory activity.

PMID- 11441188
TI  - Dietary potassium intake and risk of stroke in US men and women: National Health
      and Nutrition Examination Survey I epidemiologic follow-up study.
AB  - BACKGROUND AND PURPOSE: The few prospective studies that have explored the
      association between dietary intake of potassium and risk of stroke have reported
      inconsistent findings. This study examines the relationship between dietary
      potassium intake and the risk of stroke in a representative sample of the US
      general population. METHODS: Study participants included 9805 US men and women
      who participated in the first National Health and Nutrition Examination Survey
      (NHANES I) Epidemiologic Follow-Up Study. Dietary potassium and total energy
      intake were estimated at baseline by using a 24-hour dietary recall. Incidence
      data for stroke and coronary heart disease were obtained from medical records and
      death certificates. RESULTS: Over an average of 19 years of follow up, 927 stroke
      events and 1847 coronary heart disease events were documented. Overall, stroke
      hazard was significantly different among quartiles of potassium intake
      (likelihood ratio P=0.03); however, a test of linear trend across quartiles did
      not reach a customary level of statistical significance (P=0.14). Participants
      consuming a low potassium diet at baseline (<34.6 mmol potassium per day)
      experienced a 28% higher hazard of stroke (hazard ratio 1.28, 95% CI 1.11 to
      1.47; P<0.001) than other participants, after adjustment for established
      cardiovascular disease risk factors. CONCLUSIONS: These findings suggest that low
      dietary potassium intake is associated with an increased risk of stroke. However,
      the possibility that the association is due to residual confounding cannot be
      entirely ruled out in this observational study.

PMID- 11441189
TI  - Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral
      infarction in the Japanese.
AB  - BACKGROUND AND PURPOSE: Lipid and lipoprotein abnormalities have been implicated
      in the pathogenesis of ischemic cerebrovascular disease and atherosclerosis.
      Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein
      metabolism. Several studies have recently reported the presence of a relationship
      between Ser447Stop mutation of LPL and coronary artery disease. Other
      polymorphisms (HindIII and PvuII) of the LPL gene have already been shown to
      correlate significantly with dyslipidemia. We investigated whether these
      polymorphisms are associated with increased risk of ischemic cerebrovascular
      disease (CVD). METHODS: We recruited 177 CVD patients (atherothrombotic
      infarction, n=71; cardioembolic infarction, n=30; lacunar infarction, n=76) and
      177 healthy control subjects. Subjects were genotyped for the Ser447Stop mutation
      and for HindIII/PvuII restriction fragment length polymorphisms of the LPL gene,
      and the findings were investigated for associations with the clinical subtypes of
      CVD and with lipid levels. RESULTS: The Ser447Stop mutation correlated
      significantly with CVD (0.107 versus 0.158; P=0.035). For the CG+GG versus CC
      genotype, the odds ratio between control subjects and CVD patients with
      atherothrombotic infarction was 0.42 (95% CI, 0.18 to 0.99) (P=0.046). Serum HDL
      cholesterol and triglyceride levels did not correlate significantly with the
      Ser447Stop genotype. HindIII polymorphism correlated significantly with CVD
      (0.234 versus 0.169; P=0.031), but the frequency of PvuII polymorphism was not
      significantly different between groups. CONCLUSIONS: Our results suggest that the
      Ser447Stop mutation of the LPL gene is a novel genetic marker for low risk of
      atherothrombotic cerebral infarction.

PMID- 11441190
TI  - Possible effect of DRGs on the classification of stroke: implications for
      epidemiological surveillance.
AB  - BACKGROUND AND PURPOSE: Accurate data on the distribution of stroke subtypes are
      essential for understanding the forces driving recent morbidity and mortality
      trends. The introduction of diagnosis-related groups (DRGs) in the 1980s may have
      affected the distribution of stroke subtypes as defined by International
      Classification of Diseases, Ninth Revision (ICD-9), discharge diagnosis codes.
      METHODS: The Pawtucket Heart Health Program cardiovascular surveillance data were
      used to examine trends in stroke classification for 1980 to 1991 in relation to
      the introduction of DRGs in 2 communities in Massachusetts and Rhode Island,
      where DRGs were implemented 2 years apart. Included were all hospital discharges
      for residents aged 35 to 74 with a primary ICD-9 diagnosis of 431 to 432, 434, or
      436 to 437 (N=1386 in Rhode Island, N=1839 in Massachusetts). RESULTS: In each
      state, concurrently with the introduction of DRGs, the proportion of strokes
      classified as cerebral occlusion (ICD-9 434.0 to 434.9) increased, and the
      proportion classified as acute but ill-defined (ICD-9 436.0 to 436.9) decreased.
      Before DRGs, 30.0% of strokes in Rhode Island and 26.6% in Massachusetts were
      classified as cerebral occlusion, whereas 51.8% in Rhode Island and 51.7% in
      Massachusetts were classified as acute ill defined. After DRGs were instituted,
      the proportions of cerebral occlusion and acute, ill-defined stroke,
      respectively, were 70.9% and 8.5% in Rhode Island and 74.1% and 7.7% in
      Massachusetts (chi(2), all P<0.001). The proportions of strokes classified as
      intracerebral hemorrhage or transient cerebral ischemia remained constant.
      CONCLUSIONS: The implementation of DRGs may have influenced coding of strokes to
      the ICD-9. Findings highlight the limitations of hospital discharge data for
      evaluating stroke subtypes and demonstrate the need for community-based
      surveillance for monitoring specific trends in stroke.

PMID- 11441191
TI  - Socioeconomic status and ischemic stroke: The FINMONICA Stroke Register.
AB  - BACKGROUND AND PURPOSE: It has been shown that low socioeconomic status is
      associated with death from stroke. More-detailed data have, however, remained
      scanty. The purpose of the present study was to examine the association of
      socioeconomic status with ischemic stroke. Besides mortality, we analyzed the
      incidence, case-fatality ratio, and prognosis of ischemic stroke events. METHODS:
      Our population-based study included 6903 first stroke events registered by the
      FINMONICA Stroke Register in 3 areas of Finland during 1983 to 1992. Indicators
      of socioeconomic status, such as taxable income and education, were obtained by
      record linkage of the stroke register data with files of Statistics Finland.
      RESULTS: Incidence, case-fatality ratio, and mortality rates for ischemic stroke
      were all inversely related to income. Furthermore, 28 days after the onset of
      symptoms, a greater proportion of patients with low income than of those with
      high income was still in institutionalized care and/or in need of help for their
      activities of daily living. Population-attributable risk of the incidence of
      first ischemic stroke due to low socioeconomic status was 36% for both sexes. For
      the death from first ischemic stroke, it was 56% for both sexes. CONCLUSIONS:
      Persons with low socioeconomic status have considerable excess rates of morbidity
      and mortality from ischemic stroke in Finland. A reduction in this excess could
      markedly decrease the burden of ischemic stroke to the society and thus
      constitute an important public health improvement.

PMID- 11441192
TI  - Trends in incidence and case fatality rates of aneurysmal subarachnoid hemorrhage
      in Izumo City, Japan, between 1980-1989 and 1990-1998.
AB  - BACKGROUND AND PURPOSE: With aging of the population, the profile of subarachnoid
      hemorrhage (SAH) is likely to change; however, evaluation of long-term trends for
      incidence and case fatality rates of SAH is still limited. METHODS: We compared
      the incidence and case fatality rates of aneurysmal SAH during the 9-year period
      1990-1998 with those during the 10-year period 1980-1989 in Izumo City, Japan.
      RESULTS: During 1980-1989 and 1990-1998, we diagnosed 170 and 188 patients as
      having aneurysmal SAH, respectively. The percentage of very elderly patients aged
      >/=80 years increased from 5% (8 patients) during 1980-1989 to 18% (33 patients)
      during 1990-1998 (P<0.001). The age-specific incidence rate of SAH has a tendency
      to increase with increasing age. The crude and the age- and sex-adjusted
      incidence rates using the 1995 population statistics for Japan were 21 and 23 per
      100 000/y for all ages during 1980-1989 and 25 and 23 per 100 000/y during 1990
      1998, respectively. The 3-month case fatality rate of patients aged </=79 years
      decreased from 38% during 1980-1989 to 26% during 1990-1998 (P=0.021), whereas
      the case fatality rates in patients aged >/=80 years were very high (63% and 79%,
      respectively) regardless of study periods. Consequently, the overall case
      fatality rates for patients with SAH were similar for the 2 study periods (39%
      and 36%). CONCLUSIONS: The age- and sex-adjusted incidence rates of aneurysmal
      SAH were stable over the 19-year period since 1980 and, despite improvement of
      outcome in patients aged </=79 years, the overall case fatality rate was not
      lower because the improvements were counterbalanced by increasing numbers of very
      elderly patients

PMID- 11441193
TI  - Stroke after coronary artery bypass: incidence, predictors, and clinical outcome.
AB  - BACKGROUND AND PURPOSE: Early postoperative stroke is a serious adverse event
      after coronary artery bypass grafting (CABG). This study sought to investigate
      risk factors, prevalence, and prognostic implications of postoperative stroke in
      patients undergoing CABG. METHODS: We investigated the predictors of
      postoperative stroke (n=333, 2%) in 16 528 consecutive patients who underwent
      CABG between September 1989 and June 1999 in our institution. Predictors of
      postoperative stroke were identified by logistic regression analysis. RESULTS:
      Among the preoperative and postoperative factors, significant correlates of
      stroke included (1) chronic renal insufficiency (P<0.001), (2) recent myocardial
      infarction (P=0.01), (3) previous cerebrovascular accident (P<0.001), (4) carotid
      artery disease (P<0.001), (5) hypertension (P<0.001), (6) diabetes (P=0.001), (7)
      age >75 years (P=0.008), (8) moderate/severe left ventricular dysfunction
      (P=0.01), (9) low cardiac output syndrome (P<0.001), and (10) atrial fibrillation
      (P<0.001). Postoperative stroke was associated with longer postoperative stay
      (11+/-4 versus 7+/-3 days for patients without stroke, P<0.001) and with higher
      in-hospital mortality (14% versus 2.7% for patients without stroke; P<0.001).
      CONCLUSIONS: Stroke after CABG is associated with high short-term morbidity and
      mortality. Increased stroke risk can be predicted by preoperative and
      postoperative clinical factors.

PMID- 11441194
TI  - Effect of apolipoprotein E genotype on cerebral autoregulation during
      cardiopulmonary bypass.
AB  - BACKGROUND AND PURPOSE: The presence of the apolipoprotein E epsilon4 (apoE4)
      allele has been associated with cognitive decline after cardiac surgery. We
      compared autoregulation of cerebral blood flow (CBF), cerebral metabolic rate for
      oxygen (CMRO(2)), and arterial-venous oxygen content difference [C(A-V)O(2)],
      during cardiopulmonary bypass (CPB) in patients with and without the apoE4 allele
      to help define the mechanism of association with cognitive decline. METHODS: One
      hundred fifty-four patients underwent coronary artery bypass grafting with CPB,
      nonpulsatile flow, and alpha-stat management. CBF was measured by using (133)Xe
      washout methods. C(A-V)O(2), CMRO(2), and oxygen delivery were calculated.
      Pressure-flow autoregulation was tested by using 2 CBF measurements at stable
      hypothermia: the first at stable mean arterial pressure (MAP) and the second 15
      minutes later, when MAP had increased or decreased >/=20%. Metabolism-flow
      autoregulation was tested by varying the temperature and measuring the coupling
      of CBF and CMRO(2). RESULTS: In patients with (n=41) or without (n=113) the apoE4
      allele, there were no differences in CBF, CMRO(2), C(A-V)O(2), pressure-flow and
      metabolism-flow autoregulation corrected for age, gender, non-insulin-dependent
      diabetes, hemoglobin, CPB time, and temperature. CONCLUSIONS: We conclude that
      apoE genotype does not affect global CBF and oxygen delivery/extraction during
      CPB, which suggests that other mechanisms are responsible for the apoE isoform
      related neurocognitive dysfunction seen in patients undergoing CPB.

PMID- 11441195
TI  - Accuracy of in vivo carotid B-mode ultrasound compared with pathological
      analysis: intima-media thickening, lumen diameter, and cross-sectional area.
AB  - BACKGROUND AND PURPOSE: This study aimed to determine the correlation of in vivo
      ultrasound measurements of intima-media thickening (IMT), lumen diameter, and
      cross-sectional area of the common carotid artery (CCA) with corresponding
      measurements obtained by gross pathology and histology. METHODS: Sixty-six
      moribund neurological patients (mean age 71 years) underwent B-mode ultrasound of
      the CCA a few days before death. During autopsy, carotid specimens were removed
      in toto. Carotid arteries were ligated and cannulated for injection of a
      hydrophilic embedding material under standardized conditions. The carotid
      bifurcation was frozen and cut manually in 3-mm cross slices. Digital image
      analysis was carried out to determine the diameter and the cross-sectional area
      of the frozen slices of the CCA. IMT was assessed by light microscope. Ultrasonic
      and planimetric data were compared. RESULTS: Mean measurements of lumen diameter
      and cross-sectional area were 7.13+/-1.27 mm and 0.496+/-0.167 cm(2),
      respectively, by ultrasound, and 7.81+/-1.45 mm and 0.516+/-0.194 cm(2),
      respectively, by planimetric analysis of the unfixed redistended carotid arteries
      (R(2)=0.389 and 0.497). The mean IMT was 1.005+/-0.267 mm by ultrasound and
      0.67+/-0.141 mm histologically, resulting in a mean difference of -31%.
      CONCLUSIONS: Transcutaneous B-mode ultrasound provides a reliable approach for in
      vivo measurements of the cross-sectional area and, less exactly, of the lumen
      diameter of the CCA. Compared with histological results, in vivo ultrasound
      measurements of the IMT are systematically larger.

PMID- 11441196
TI  - Sex differences in carotid bifurcation anatomy and the distribution of
      atherosclerotic plaque.
AB  - BACKGROUND AND PURPOSE: Plaque formation at arterial bifurcations depends on
      vessel anatomy, particularly the relative sizes of the branches, and the ratio of
      the outflow to inflow area. The facts that carotid plaque is more common in men
      and that carotid bruits in the absence of stenosis are more frequent in women
      raise the possibility that there are sex differences in carotid bifurcation
      anatomy. We studied 5395 angiograms from the European Carotid Surgery Trial.
      METHODS: To minimize secondary changes we excluded angiograms with >/=50%
      stenosis and also studied vessels with no disease. We measured arterial diameters
      at disease-free points and calculated the following ratios: internal/common
      (ICA/CCA); external/common (ECA/CCA); internal/external (ICA/ECA) carotid
      arteries; carotid bulb/CCA; and outflow/inflow area. We related these to sex and
      also studied the distribution of plaque in the whole trial population. RESULTS:
      Among 2930 angiograms with <50% stenosis, the mean ICA/CCA ratio, ICA/ECA ratio,
      and outflow/inflow area ratio were larger in women than in men (all P<0.0001).
      The findings were similar in 622 bifurcations without atheroma. There were also
      differences in the distribution of plaque, with men more likely to have the
      maximum stenosis distal to the carotid bulb (odds ratio, 2.29; 95% CI, 1.33 to
      4.01; P=0.001) and women more likely to have stenosis of the ECA (odds ratio,
      1.54; 95% CI, 1.30 to 1.85; P<0.0001). CONCLUSIONS: Sex differences in carotid
      bifurcation anatomy are not limited to absolute vessel size. In addition, the
      outflow to inflow area ratio is bigger in women, and relative to the CCA and ECA,
      women have larger ICAs than men. Irrespective of whether these differences are
      congenital or acquired, they may partly explain the sex differences that we found
      in the distribution of plaque and the sex differences in the prevalence of
      carotid atheroma in the general population.

PMID- 11441197
TI  - Is carotid intima-media thickness useful in cardiovascular disease risk
      assessment? The Rotterdam Study.
AB  - BACKGROUND AND PURPOSE: We determined the contribution of common carotid intima
      media thickness (IMT) in the prediction of future coronary heart disease and
      cerebrovascular disease when added to established risk factors. METHODS: We used
      data from a nested case-control study comprising 374 subjects with either an
      incident stroke or a myocardial infarction and 1496 controls. All subjects were
      aged 55 years and older and participated in the Rotterdam Study. Mean follow-up
      was 4.2 years (range, 0.1 to 6.5 years). We evaluated which correlates of
      coronary heart disease and cerebrovascular disease contribute to the prediction
      of either a new incident myocardial infarction or a stroke. Logistic regression
      modeling and the area under the receiver operating characteristic curve (ROC
      area) were used to quantify the predictive value of the established risk factors
      and the added value of IMT. RESULTS: The ROC area of a model with age and sex
      only was 0.65 (95% CI, 0.62 to 0.69). Independent risk factors were previous
      myocardial infarction and stroke, diabetes mellitus, smoking, systolic blood
      pressure, diastolic blood pressure, and total and HDL cholesterol levels. These
      risk factors increased the ROC area from 0.65 to 0.72 (95% CI, 0.69 to 0.75).
      This model correctly predicted 17% of all subjects with coronary heart disease
      and cerebrovascular disease. When common carotid IMT was added to the previous
      model, the ROC area increased to 0.75 (95% CI, 0.72 to 0.78). When only the IMT
      measurement was used, the ROC area was 0.71 (95% CI, 0.68 to 0.74), and 14% of
      all subjects were correctly predicted. There was no difference in ROC area when
      different measurement sites were used. CONCLUSIONS: Adding IMT to a risk function
      for coronary heart disease and cerebrovascular disease does not result in a
      substantial increase in the predictive value when used as a screening tool.

PMID- 11441198
TI  - Angiotensin-converting enzyme inhibition with enalapril slows progressive intima
      media thickening of the common carotid artery in patients with non-insulin
      dependent diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Whether angiotensin-converting enzyme (ACE) inhibitors
      have any clinically significant antiatherogenic effects in humans remains
      unproven. We undertook a prospective randomized clinical trial of 98 patients
      with non-insulin-dependent diabetes mellitus (NIDDM) to examine the efficacy of
      ACE inhibition with enalapril for preventing intima-media (IM) thickening of the
      carotid wall as measured ultrasonographically. METHODS: Ninety-eight NIDDM
      patients were randomly assigned either to enalapril at 10 mg/d (n=48) or to a
      control group (n=50); the planned duration of the trial was 2 years. All patients
      were seen at baseline (study entry) and 2 subsequent formal annual evaluations,
      in addition to standard clinical management for NIDDM. IM thickening and vascular
      lumen diameters were determined for all patients on the basis of baseline and 2
      subsequent annual evaluations with carotid ultrasonography. We performed an
      intent-to-treat analysis to assess changes in IM thickening over the course of
      the study. RESULTS: Annual IM thickening measurements of the right and left
      common carotid arteries were 0.01+/-0.02 and 0.01+/-0.02 mm/y in the enalapril
      treated group and 0.02+/-0.03 and 0.02+/-0.02 mm/y in the control group,
      respectively (P<0.05). From regression analysis, annual IM thickening was found
      to be predicted by enalapril use, sex, and insulin use (F(3,94)=3.86, P=0.012).
      When we controlled for these other variables, enalapril use reduced annual IM
      thickening of right and left common carotid arteries by 0.01+/-0.004 mm/y
      relative to the control group over the course of this study. CONCLUSIONS: Long
      term treatment with an ACE inhibitor (enalapril) slows progressive IM thickening
      of the common carotid artery in NIDDM patients.

PMID- 11441199
TI  - Muscle tensing during standing: effects on cerebral tissue oxygenation and
      cerebral artery blood velocity.
AB  - BACKGROUND AND PURPOSE: When standing up causes dizziness, tensing of the leg
      muscles may alleviate the symptoms. We tested the hypothesis that leg tensing
      improves orthostatic tolerance via enhanced cerebral perfusion and oxygenation.
      METHODS: In 10 healthy young adults, the effects of leg tensing on transcranial
      Doppler-determined middle cerebral artery (MCA) mean blood velocity (V(mean)) and
      the near-infrared spectroscopy-determined frontal oxygenation (O(2)Hb) were
      assessed together with central circulatory variables and an arterial pressure low
      frequency (LF) (0.07 to 0.15 Hz) domain evaluation of sympathetic activity.
      RESULTS: Standing up reduced central venous pressure by (mean+/-SEM) 4.3+/-2.6 mm
      Hg, stroke volume by 49+/-7 mL, cardiac output by 1.9+/-0.4 L/min, and mean
      arterial pressure at MCA level by 9+/-4 mm Hg, whereas it increased heart rate by
      30+/-4 beats per minute (P<0.05). MCA V(mean) declined from 67+/-4 to 56+/-3
      cm/s, O(2)Hb decreased by 7+/-2.8%, and LF spectral power increased (P<0.05). Leg
      tensing increased central venous pressure by 1.4+/-2.7 mm Hg and cardiac output
      by 1.8+/-0.4 L/min with no significant effect on blood pressure, whereas heart
      rate decreased by 11+/-3 beats per minute (P<0.05). MCA V(mean) increased to 63+/
      3 cm/s and O(2)Hb increased by 2.1+/-2.6%, whereas LF power declined (P<0.05).
      Within 2 minutes after leg tensing, these effects had disappeared. CONCLUSIONS:
      During standing, tensing of the leg muscles attenuates a reduction in cerebral
      perfusion and oxygenation as it stabilizes central circulatory variables and
      reduces sympathetic activity.

PMID- 11441200
TI  - Effect of collateral blood flow and cerebral vasomotor reactivity on the outcome
      of carotid artery occlusion.
AB  - BACKGROUND AND PURPOSE: Evidence suggests that an alteration in cerebral
      hemodynamics plays a relevant role in the occurrence of stroke in patients with
      carotid occlusion. The purpose of the present study was to evaluate the
      relationships among baseline characteristics, type and number of collateral
      pathways, cerebral vasomotor reactivity (VMR), and outcome of patients with
      carotid occlusion. METHODS: One hundred four patients with symptomatic or
      asymptomatic internal carotid artery occlusion were followed up prospectively for
      a median period of 24 months. Cerebral VMR to apnea was calculated with
      transcranial Doppler ultrasonography by means of the breath-holding index (BHI)
      in the middle cerebral arteries. The patency of the 3 major intracranial
      collateral vessels was also evaluated. RESULTS: During the follow-up period, 18
      patients experienced an ischemic stroke ipsilateral to internal carotid artery
      occlusion. Among factors considered, only older age, number of collateral
      pathways, and BHI values in the middle cerebral artery ipsilateral to the
      occluded side were significantly associated with the risk of ipsilateral stroke
      (P<0.001, P=0.008, and P<0.001, respectively; multiple Cox regression analysis).
      A normal VMR and favorable prognosis characterized patients with full collateral
      development; in this group, no patient experienced an ischemic event. On the
      other hand, an impaired VMR and increased probability of experiencing a stroke
      were found in patients without collateral pathways; the annual risk of
      ipsilateral stroke in this group was 32.7%. Patients with 1 or 2 collateral
      pathways showed a different VMR ranging from normal to strongly reduced BHI
      values. The ipsilateral stroke event risk was 17.5% in patients with 1 collateral
      vessel and 2.7% in patients with 2 collateral pathways. In this case, the risk of
      cerebrovascular events occurring during the follow-up period was significantly
      related to VMR. CONCLUSIONS: These data suggest that cerebral hemodynamic status
      in patients with carotid occlusive disease is influenced by both individual
      anatomic and functional characteristics. The planning of strategies to define the
      risk profile and any attempt to influence patients' outcome should be based on
      the evaluation of the intracranial hemodynamic adaptive status, with particular
      attention to the number of collateral vessels and the related VMR.

PMID- 11441201
TI  - Enhanced endothelium-dependent vasodilation in Fabry disease.
AB  - BACKGROUND AND PURPOSE: Fabry disease is an X-linked lysosomal storage disease
      secondary to deficiency of alpha-galactosidase A with resulting glycolipid
      accumulation, particularly globotriaosylceramide in arterial smooth muscle and
      endothelial cells. A systemic vasculopathy, including early-onset stroke, is
      prevalent without a clear pathogenesis. METHODS: Seventeen normotensive and
      normocholesterolemic hemizygous Fabry patients (aged 21 to 49 years) and 13
      control subjects (aged 21 to 48 years) were investigated by venous
      plethysmography, allowing assessment of forearm blood flow. Plethysmographic
      measurements were obtained at baseline and during intra-arterial infusion of
      acetylcholine and sodium nitroprusside both with and without N(G)-monomethyl-L
      arginine (L-NMMA). RESULTS: Forearm blood flow was significantly higher in
      patients than in control subjects at all 3 acetylcholine doses (P=0.014).
      Patients had a greater response to acetylcholine even after the addition of L
      NMMA (P=0.036). CONCLUSIONS: These results demonstrate an increased endothelium
      mediated vascular reactivity in Fabry disease. The increased vessel response to
      acetylcholine with and without L-NMMA suggests altered functionality of non-NO
      endothelium-dependent vasodilatory pathways.

PMID- 11441202
TI  - Is patent foramen ovale a family trait? A transcranial Doppler sonographic study.
AB  - BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) is a frequent finding in young
      patients with stroke. The aim of this study was to assess whether PFO is a family
      trait. METHODS: Sixty-two consecutive patients younger than 60 years of age with
      ischemic stroke and 62 age and gender-matched control siblings were examined by
      means of contrast transcranial Doppler (TCD) of the middle cerebral artery, using
      a standardized protocol. The reliability of TCD examination in our laboratory was
      assessed against transesophageal echocardiography (TEE). All TCD recordings were
      reviewed by a blinded experienced observer from another center. Disagreements
      between readers were resolved by unblinded consensus review. RESULTS: Siblings of
      patients with PFO had a significantly higher prevalence of PFO than had siblings
      of patients without PFO (61.5% versus 30.6%; OR 3.64 [1.3 to 10.5]; P=0.015). The
      kappa statistics indicated that agreement of pairs (patients/control siblings)
      was not due to chance. The strength of the association was sex dependent. In
      women pairs, prevalence of a PFO was 76.5% in siblings of patients with PFO and
      25% in siblings of patients without PFO, giving an OR of 9.8 (95% CI 2 to 47.9;
      P<0.01). In contrast, in men, no significant difference was observed in the
      prevalence of PFO between siblings of patients with or without PFO (respectively
      33.3% and 35%), giving an OR of 0.9 (95% CI 0.2 to 4.9; P=0.9). CONCLUSIONS: This
      study suggests that, in women, PFO is a family trait.

PMID- 11441203
TI  - Cerebral vasoreactivity and internal carotid artery flow help to identify
      patients at risk for hyperperfusion after carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Hyperperfusion syndrome is a rare but potentially
      devastating complication after carotid endarterectomy (CEA). The aim of this
      study was to investigate whether preoperative measurement of cerebral
      vasoreactivity (CVR) and intraoperative measurement of internal carotid artery
      (ICA) flow could identify patients at risk for hyperperfusion after CEA. METHODS:
      For 26 patients with unilateral ICA stenosis >/=70%, cerebral blood flow (CBF)
      and CVR were investigated before and 1 month after CEA, with resting and
      acetazolamide-challenge single-photon emission CT. CBF on the first postoperative
      day was also measured. ICA flow was measured before and after reconstruction by
      electromagnetic flowmeter during surgery. RESULTS: Ipsilateral CBF on the first
      postoperative day significantly increased relatively (56.6+/-53.2%) as well as
      absolutely (37.9+/-8.8 to 57.7+/-18.0 mL/100 g per minute) in the reduced CVR
      group (CVR <12%) but not in the normal CVR group (CVR >/=12%) (10.3+/-15.5% and
      40.6+/-7.9 to 43.9+/-5.7 mL/100 g per minute, respectively). One month later,
      this difference almost disappeared. Two patients showed ipsilateral CBF increase
      of >/=100%. A significant association of intracerebral steal with hyperperfusion
      (CBF increase >/=100%) on the first postoperative day was also observed. ICA flow
      increase after reconstruction significantly correlated with CBF increase on the
      first postoperative day in the reduced CVR group but not in the normal CVR group.
      The threshold of ICA flow increase for hyperperfusion was estimated to be 330
      mL/min in the reduced CVR group. CONCLUSIONS: Single-photon emission CT with
      acetazolamide challenge and ICA flow measurement during surgery could identify
      patients at risk for hyperperfusion after CEA, in whom careful monitoring and
      control of blood pressure should be initiated even intraoperatively.

PMID- 11441204
TI  - Middle cerebral artery occlusion and reperfusion in primates monitored by
      microdialysis and sequential positron emission tomography.
AB  - BACKGROUND AND PURPOSE: In a previous investigation concerning the hemodynamic
      and metabolic changes over time displayed by sequential positron emission
      tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate
      model, a metabolic threshold for irreversible ischemia could be identified
      (reduction of metabolic rate of oxygen [CMRO(2)] to approximately 60% of the
      contralateral hemisphere). To evaluate the potential of microdialysis (MD) as an
      instrument for chemical brain monitoring, the aim of this subsequent study was to
      relate the chemical changes in MD levels directly to the regional metabolic
      status (CMRO(2) above or below the metabolic threshold) and the occurrence of
      reperfusion, as assessed by PET. METHODS: Continuous MD (2 probes in each brain)
      and sequential PET measurements were performed during MCA occlusion (2 hours) and
      18 hours (mean) of reperfusion in 8 monkeys (Macaca mulatta). Energy-related
      metabolites (lactate, pyruvate, and hypoxanthine) and glutamate were analyzed.
      The MD probe regions were divided into 3 categories on the basis of whether
      CMRO(2) was below or above 60% of the contralateral region (metabolic threshold
      level) during MCA occlusion and whether reperfusion was obtained: severe ischemia
      with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra
      with reperfusion (n=5). RESULTS: The lactate/pyruvate ratio, hypoxanthine, and
      glutamate showed similar patterns. MD probe regions with severe ischemia and
      reperfusion and probe regions with severe ischemia and no reperfusion displayed
      high and broad peaks, respectively, during MCA occlusion, and the levels almost
      never decreased to baseline. Penumbra MD probe regions displayed only slight
      transient increases during MCA occlusion and returned to baseline. CONCLUSIONS:
      This experimental study of focal ischemia showed that the extracellular changes
      of energy-related metabolites and glutamate differed depending on the ischemic
      state of the brain during MCA occlusion and depending on whether reperfusion
      occurred. If MD proves to be beneficial in clinical practice, it appears
      important to observe relative changes over time.

PMID- 11441205
TI  - Perfusion magnetic resonance imaging maps in hyperacute stroke: relative cerebral
      blood flow most accurately identifies tissue destined to infarct.
AB  - BACKGROUND AND PURPOSE: In ischemic stroke, perfusion-weighted imaging (PWI) and
      diffusion-weighted imaging (DWI) provide important pathophysiological
      information. A PWI>DWI mismatch pattern suggests the presence of salvageable
      tissue. However, improved methods for distinguishing PWI>DWI mismatch tissue that
      is critically hypoperfused from benign oligemia are required. METHODS: We
      investigated the usefulness of maps of relative cerebral blood flow (rCBF),
      volume (rCBV), and mean transit time (rMTT) to predict transition to infarction
      in hyperacute (<6 hours) stroke patients with PWI>DWI mismatch patterns.
      Semiquantitative color-thresholded analysis was used to measure hypoperfusion
      volumes, including increasing color signal intensity thresholds of rMTT delay,
      which were compared with infarct expansion, outcome infarct size, and clinical
      status. RESULTS: Acute rCBF lesion volume had the strongest correlation with
      final infarct size (r=0.91, P<0.001) and clinical outcome (r=0.67, P<0.01). There
      was a trend for acute rCBF>DWI mismatch volume to overestimate infarct expansion
      between the acute and outcome study (P=0.06). Infarct expansion was
      underestimated by acute rCBV>DWI mismatch (P<0.001). When rMTT lesions included
      tissue with moderately prolonged transit times (mean delay 4.3 seconds, signal
      intensity values 50% to 70%), infarct expansion was overestimated. In contrast,
      when rMTT lesions were restricted to more severely prolonged transit times (mean
      delay 6.1 seconds, signal intensity >70%), these regions progressed to infarction
      in all except 1 patient, but infarct expansion was underestimated (P<0.001).
      CONCLUSIONS: The acute rCBF lesion most accurately identified tissue in the
      PWI>DWI mismatch region at risk of infarction. Color-thresholded PWI maps show
      potential for use in an acute clinical setting to prospectively predict tissue
      outcome.

PMID- 11441206
TI  - Prospective value of perfusion and X-ray attenuation imaging with single-photon
      emission and transmission computed tomography in acute cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to test the hypothesis
      that perfusion single-photon emission computed tomography (SPECT), carried out in
      addition to transmission computed tomography (TCT), improves the predictive value
      of brain imaging within the therapeutically relevant time window after acute
      cerebral ischemia. METHODS: Using TCT and [(99m)Tc]ethyl cysteinate dimer (ECD)
      SPECT within 6 hours after symptom onset, we examined 108 patients (44 women, 64
      men; mean age 65+/-13 years) with acute ischemic stroke attributed to the
      territory of the middle cerebral artery (MCA). In each case, 3 experts
      prospectively evaluated the early SPECT and TCT images. We correlated these
      ratings with follow-up TCT findings for the final infarction as well as with
      clinical outcome (Scandinavian Stroke Scale, Barthel Index, Modified Rankin
      Scale) after 30 and 90 days. RESULTS: Severe activity deficits on SPECT, not
      caused by local atrophy on TCT, were the best predictors (positive predictive
      value [PPV ]94%, 95% CI 89% to 99%; negative predictive value [NPV] 90%, 95% CI
      78% to 100%; P<0.001) for evolving cerebral infarction. Complete MCA infarctions
      were predicted with significantly higher accuracy with early SPECT (area under
      receiver operating characteristic curve [AUC] index 0.91) compared with early TCT
      (AUC index 0.77) and clinical parameters (AUC index 0.73, P<0.05). Logistic
      regression analysis revealed 1 independent predictor for completed MCA territory
      infarction: SPECT activity deficits in the corresponding areas (PPV 88%, 95% CI
      65% to 100%; NPV 96%, 95% CI 92% to 100%; P<0.001). Furthermore, death after
      stroke was optimally predicted by [(99m)Tc]ECD-SPECT. Clinical outcome up to 90
      days after the stroke event best correlated with the degree of activity deficits
      in early SPECT (r=0.53, P<0.001). CONCLUSIONS: [(99m)Tc]ECD brain perfusion SPECT
      that completes TCT definitely improves the predictive value of brain imaging
      after acute cerebral ischemia. Thus, the combined imaging of brain edema and of
      cerebral perfusion early after stroke is recommended for clinical use.

PMID- 11441207
TI  - Recommendations for clinical trial evaluation of acute stroke therapies.
AB  - The development of therapies for acute ischemic stroke has achieved a few notable
      successes and, unfortunately, many unsuccessful efforts. Many valuable lessons
      for the future assessment of new acute stroke therapies can be gleaned from the
      positive and negative prior trials. Phase I and II trials must be carefully
      designed and implemented to derive relevant, valuable information needed to
      proceed to phase III trials with promising interventions. The phase III trial
      should evaluate drug efficacy in an appropriately targeted stroke population
      evaluated by a meaningful and reliable outcome measure. Combinations of various
      types of stroke therapies will likely be increasingly assessed in future trials
      that are designed and implemented by cooperative efforts between the
      pharmaceutical industry, government agencies, academic advisors and clinical
      investigators. The chances for future success in demonstrating efficacy with
      acute stroke therapies will be enhanced by carefully conceived, scientifically
      based clinical trials. The recommendations contained in this document may help to
      focus attention on how to achieve the goal of developing an expanding number of a
      effective and safe acute stroke therapies.

PMID- 11441208
TI  - Effect of paracetamol (acetaminophen) on body temperature in acute ischemic
      stroke: a double-blind, randomized phase II clinical trial.
AB  - BACKGROUND AND PURPOSE: Body temperature is a strong predictor of outcome in
      acute stroke. However, it is unknown whether antipyretic treatment leads to early
      and clinically worthwhile reduction of body temperature in patients with acute
      stroke, especially when they have no fever. The main purpose of this trial was to
      study whether early treatment of acute ischemic stroke patients with
      acetaminophen (paracetamol) reduces body temperature. METHODS: Seventy-five
      patients with acute ischemic stroke confined to the anterior circulation were
      randomized to treatment with either 500 mg (low dose) or 1000 mg (high dose)
      acetaminophen or with placebo, administered as suppositories 6 times daily during
      5 days. Body temperatures were measured with a rectal electronic thermometer at
      the start of treatment and after 24 hours and with an infrared tympanic
      thermometer at 2-hour intervals during the first 24 hours and at 6-hour intervals
      thereafter. The primary outcome measure was rectal temperature at 24 hours after
      the start of treatment. RESULTS: Treatment with high-dose acetaminophen resulted
      in 0.4 degrees C lower body temperatures than placebo treatment at 24 hours (95%
      CI 0.1 degrees C to 0.7 degrees C). The mean reduction from baseline temperature
      with high-dose acetaminophen was 0.3 degrees C (95% CI 0 degrees C to 0.6 degrees
      C) higher than that in placebo-treated patients. Treatment with low-dose
      acetaminophen did not result in lower body temperatures. After 5 days of
      treatment, no differences in temperature were found between the placebo and the
      high- or low-dose acetaminophen groups. CONCLUSIONS: Treatment with a daily dose
      of 6000 mg acetaminophen may result in a small, but potentially beneficial,
      decrease in body temperature shortly after ischemic stroke, even in normothermic
      and subfebrile patients. Further studies should determine whether this effect is
      reproducible and whether early reduction of body temperature leads to improved
      outcome.

PMID- 11441209
TI  - Neuroprotective effect of sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)
      piperidine (PPBP) is linked to reduced neuronal nitric oxide production.
AB  - BACKGROUND AND PURPOSE: The potent final sigma(1)-receptor ligand 4-phenyl-1-(4
      phenylbutyl) piperidine (PPBP) provides neuroprotection in experimental stroke.
      We tested the hypothesis that PPBP attenuates striatal tissue damage after middle
      cerebral artery occlusion (MCAO) by a mechanism involving reduction of ischemia
      evoked nitric oxide (NO) production. Furthermore, we determined whether the agent
      fails to protect ischemic brain when neuronal nitric oxide synthase (nNOS) is
      genetically deleted or pharmacologically inhibited (selective nNOS inhibitor, 7
      nitroindazole [7-NI]). METHODS: Halothane-anesthetized adult male Wistar rats
      were subjected to 2 hours of MCAO by the intraluminal filament occlusion
      technique. All physiological variables were controlled during the ischemic
      insult. In vivo striatal NO production was estimated via microdialysis by
      quantification of local, labeled citrulline recovery after labeled arginine
      infusion. In a second series of experiments, nNOS null mutants (nNOSKOs) and the
      genetically matched wild-type (WT) strain were treated with 90 minutes of MCAO.
      Brains were harvested at 22 hours of reperfusion for measurement of infarction
      volume by triphenyltetrazolium chloride histology. RESULTS: PPBP attenuated
      infarction volume at 22 hours of reperfusion in cerebral cortex and striatum and
      markedly attenuated NO production in ischemic and nonischemic striatum during
      occlusion and early reperfusion. Treatment with 7-NI mimicked the effects of
      PPBP. In WT mice, infarction volume was robustly decreased by both PPBP and 7-NI,
      but the efficacy of PPBP was not altered by pharmacological nNOS inhibition in
      combined therapy. In contrast, PPBP did not decrease infarction volume in nNOSKO
      mice. CONCLUSIONS: These data suggest that the mechanism of neuroprotection of
      PPBP in vivo is through attenuation of nNOS activity and ischemia-evoked NO
      production. Neuroprotective effects of PPBP are lost when nNOS is not present or
      is inhibited; therefore, PPBP likely acts upstream from NO generation and its
      subsequent neurotoxicity.

PMID- 11441210
TI  - Constraint-induced therapy of chronic aphasia after stroke.
AB  - Patients with chronic aphasia were assigned randomly to a group to receive either
      conventional aphasia therapy or constraint-induced (CI) aphasia therapy, a new
      therapeutic technique requiring intense practice over a relatively short period
      of consecutive days. CI aphasia therapy is realized in a communicative
      therapeutic environment constraining patients to practice systematically speech
      acts with which they have difficulty. Patients in both groups received the same
      amount of treatment (30 to 35 hours) as 10 days of massed-practice language
      exercises for the CI aphasia therapy group (3 hours per day minimum; 10 patients)
      or over a longer period of approximately 4 weeks for the conventional therapy
      group (7 patients). CI aphasia therapy led to significant and pronounced
      improvements on several standard clinical tests, on self-ratings, and on blinded
      observer ratings of the patients' communicative effectiveness in everyday life.
      Patients who received the control intervention failed to achieve comparable
      improvements. Data suggest that the language skills of patients with chronic
      aphasia can be improved in a short period by use of an appropriate massed
      practice technique that focuses on the patients' communicative needs.

PMID- 11441211
TI  - The ABILHAND questionnaire as a measure of manual ability in chronic stroke
      patients: Rasch-based validation and relationship to upper limb impairment.
AB  - BACKGROUND AND PURPOSE: Chronic hemiparetic patients often retain the ability to
      manage activities requiring both hands, either through the use of the affected
      arm or compensation with the unaffected limb. A measure of this overall ability
      was developed by adapting and validating the ABILHAND questionnaire through the
      Rasch measurement model. ABILHAND measures the patient's perceived difficulty in
      performing everyday manual activities. METHODS: One hundred three chronic (>6
      months) stroke outpatients (62% men; mean age, 63 years) were assessed (74 in
      Belgium, 29 in Italy). They lived at home and walked independently and were
      screened for the absence of major cognitive deficits (dementia, aphasia,
      hemineglect). The patients were administered the ABILHAND questionnaire, the
      Brunnstrom upper limb motricity test, the box-and-block manual dexterity test,
      the Semmes-Weinstein tactile sensation test, and the Geriatric Depression Scale.
      The brain lesion type and site were recorded. ABILHAND results were analyzed with
      the use of Winsteps Rasch software. RESULTS: The Rasch refinement of ABILHAND led
      to a change from the original unimanual and bimanual 56-item, 4-level scale to a
      bimanual 23-item, 3-level scale. The resulting ability scale had sufficient
      sensitivity to be clinically useful. Rasch reliability was 0.90, and the item
      difficulty hierarchy was stable across demographic and clinical subgroups. Grip
      strength, motricity, dexterity, and depression were significantly correlated with
      the ABILHAND measures. CONCLUSIONS: The ABILHAND questionnaire results in a valid
      person-centered measure of manual ability in everyday activities. The stability
      of the item-difficulty hierarchy across different patient classes further
      supports the clinical application of the scale.

PMID- 11441212
TI  - Assessing Wolf motor function test as outcome measure for research in patients
      after stroke.
AB  - BACKGROUND AND PURPOSE: The Wolf Motor Function Test (WMFT) is a new time-based
      method to evaluate upper extremity performance while providing insight into joint
      specific and total limb movements. This study addresses selected psychometric
      attributes of the WMFT applied to a chronic stroke population. METHODS: Nineteen
      individuals after stroke and with intact cognition and sitting balance were age-
      and sex-matched with 19 individuals without impairment. Subjects performed the
      WMFT and the upper extremity portion of the Fugl-Meyer Motor Assessment (FMA) on
      2 occasions (12 to 16 days apart), with scoring performed independently by 2
      random raters. RESULTS: The WMFT and FMA demonstrated agreement (P<0.0001)
      between raters at each session. WMFT scores for the dominant and nondominant
      extremities of individuals without impairment were different (P</=0.05) from the
      more and less affected extremities of subjects after stroke. The FMA score for
      the more affected extremity of subjects after stroke was different (P</=0.05)
      from the dominant and nondominant extremities. However, the FMA score for the
      less affected upper extremity of individuals after stroke was not different
      (P>0.05) from the dominant and nondominant extremities of individuals without
      impairment. The WMFT and FMA scores were related (P<0.02) for the more affected
      extremity in individuals after stroke. CONCLUSIONS: The interrater reliability,
      construct validity, and criterion validity of the WMFT, as used in these subject
      samples, are supported.

PMID- 11441213
TI  - Negative attitudes among short-term stroke survivors predict worse long-term
      survival.
AB  - BACKGROUND AND PURPOSE: Patients respond to serious illness in different ways. We
      wished to determine whether different attitudes toward illness are associated
      with survival after stroke. METHODS: Three hundred seventy-two stroke patients
      were identified and medically assessed as part of a randomized trial to evaluate
      a stroke family care worker. They had all survived 6 months from randomization. A
      research psychologist visited each patient and administered the Mental Adjustment
      to Stroke Scale (a self-rated attitude scale based on the Mental Adjustment to
      Cancer Scale). Disability and dependence (Barthel Index, modified Rankin Scale)
      and mood (Hospital Anxiety and Depression Scale, General Health Questionnaire 30)
      were also assessed. Patients were followed up in 1998 (3 to 5 years after the
      initial stroke) to establish their survival. We modeled the relationship between
      Mental Adjustment to Stroke scores and survival, adjusting for other factors
      associated with stroke survival. RESULTS: Eighty-two patients (22%) died within 3
      years. After adjustment for other significant factors, fatalism and
      helplessness/hopelessness were both associated with decreased survival (P=0.03
      and 0.04, respectively), but fighting spirit, anxious preoccupation, and
      denial/avoidance were not. Mood was not associated with survival. CONCLUSIONS:
      Patients' attitudes toward their illness seem to be associated with survival
      after stroke. Patients who feel that there is nothing they can do to help
      themselves 6 months after a stroke have a shorter survival. These findings need
      to be confirmed and any causal relationship between attitude and survival further
      explored in a randomized controlled trial to "improve" the attitude of stroke
      patients toward their illness.

PMID- 11441214
TI  - Spouses of first-ever stroke patients: psychological well-being in the first
      phase after stroke.
AB  - BACKGROUND AND PURPOSE: A stroke affects not only the patient but also the
      spouse. To better support the spouse during the acute phase of stroke, knowledge
      is needed about his or her experience with the situation. The aim of the present
      study was to study the well-being of the spouses of stroke patients during the
      acute state of stroke and to identify factors that may influence their well
      being. METHODS: Eighty-three consecutively enrolled spouses of first-ever stroke
      patients <75 years old participated. Their psychological well-being, measured by
      the Psychological General Well-Being Index 10 days after the stroke, was compared
      with norm values. Multiple analyses of correlation were performed to investigate
      the effects on psychological well-being of (1) age and sex, (2) level of
      impairment of the stroke patient, and (3) intrapersonal variables such as
      previous life satisfaction and view of the future. RESULTS: The study group
      showed significantly lower psychological well-being compared with norm values
      except for the dimension of general health. The variables that correlated
      significantly with the Psychological General Well-Being total score were the
      sensorimotor impairment of the stroke patient and the "view of the future." This
      view of the future also correlated significantly with the level of functional
      ability of the stroke patients. CONCLUSIONS: During the acute phase of stroke,
      the severity of the stroke has an impact on the spouse's image of his or her
      future life, whereas the individual appraisal of personal consequences and of his
      or her own coping capacity seems to have a greater impact on the psychological
      well-being of the spouses than does the objective state of disability.

PMID- 11441215
TI  - Transgenic CuZn-superoxide dismutase inhibits NO synthase induction in
      experimental subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: The expression of inducible NO synthase (iNOS) after
      experimental subarachnoid hemorrhage (SAH) has been postulated to play a critical
      role in the pathogenesis of SAH and subsequent cerebral vasospasm. The inhibitory
      effect of CuZn-superoxide dismutase (CuZn-SOD) on the induction of iNOS after SAH
      was examined by using transgenic mice overexpressing CuZn-SOD. METHODS: SOD
      transgenic mice and nontransgenic littermates were subjected to SAH by
      endovascular perforation of the left anterior cerebral artery. The iNOS mRNA
      expression after SAH was determined by reverse transcription-polymerase chain
      reaction, and the distribution of iNOS-positive cells was immunohistochemically
      examined. The nuclear expression of activated nuclear factor-kappaB, a major
      transcription factor of iNOS gene, was also immunohistochemically examined.
      RESULTS: In nontransgenic mice, SAH-induced iNOS protein and mRNA expressions in
      the arteries of basal cistern as well as in the cerebral cortex were demonstrated
      by immunohistochemistry and reverse transcription-polymerase chain reaction. SAH
      induced iNOS protein and mRNA expressions in those tissues were much reduced in
      SOD-transgenic mice compared with nontransgenic mice. Moreover, the nuclear
      expression of the activated form of nuclear factor-kappaB was
      immunohistochemically detected in the cerebral cortices of nontransgenic mice but
      not in those of SOD-transgenic mice. CONCLUSIONS: These results indicate that
      oxygen-derived free radicals, particularly superoxide, play an important role in
      the iNOS gene expression after SAH and provide a molecular basis for the
      protective role of SOD against vasospasm after SAH.

PMID- 11441216
TI  - Threshold duration of ischemia for myogenic tone in middle cerebral arteries:
      effect on vascular smooth muscle actin.
AB  - BACKGROUND AND PURPOSE: We investigated the effect of different periods of
      ischemia on the myogenic tone of middle cerebral arteries (MCAs) and tested the
      hypothesis that ischemia disrupts the actin cytoskeleton in vascular smooth
      muscle. METHODS: The MCA occlusion model was used in male Wistar rats (n=27) to
      induce different periods of ischemia (15, 30, and 120 minutes) with 24 hours of
      reperfusion. Successful occlusion was determined by laser-Doppler flowmetry. MCAs
      were then studied in vitro with a specialized arteriograph system that allowed
      control of transmural pressure and measurement of lumen diameter. After
      equilibration for 1 hour at transmural pressure of 75 mm Hg, lumen diameter was
      measured, and the amount of spontaneous myogenic tone was determined. Arteries
      were then fixed with 10% formalin while still pressurized in the arteriograph
      bath and stained for filamentous (F-) actin with fluorescently labeled
      phalloidin, a specific probe for F-actin. The amount of F-actin was quantified by
      confocal microscopy. RESULTS: The amount of tone was similar between control and
      15 minutes of ischemia (27.0+/-2.0% and 25.3+/-1.7%, respectively; P>0.05) but
      was significantly diminished after 30 and 120 minutes (11.7+/-2.0% and 8.5+/
      2.0%, respectively; P<0.01 versus control). F-actin content also decreased at the
      longer ischemic periods and correlated significantly with vascular tone (P=0.04)
      such that the lesser the tone, the lesser was the F-actin content. Fluorescence
      intensity for control and 15, 30, and 120 minutes of ischemia was (x10(7)) 3.21+/
      0.25, 2.54+/-0.32 (P>0.05), 2.32+/-0.15 (P<0.01), and 2.22+/-0.16 (P<0.01),
      respectively. CONCLUSIONS: These results demonstrate that ischemia disrupts the
      actin cytoskeleton in smooth muscle and diminishes vascular tone of MCAs in a
      threshold-dependent manner. This effect likely exacerbates brain tissue damage
      during stroke, including infarction and edema formation.

PMID- 11441217
TI  - Broad-spectrum and selective serine protease inhibitors prevent expression of
      platelet-derived growth factor-BB and cerebral vasospasm after subarachnoid
      hemorrhage: vasospasm caused by cisternal injection of recombinant platelet
      derived growth factor-BB.
AB  - BACKGROUND AND PURPOSE: Plasma serine protease cascade, including the complement
      system and thrombin, is activated in the subarachnoid space during the acute
      phase after subarachnoid hemorrhage (SAH). To examine the effect of protease
      cascade-based inflammation and subsequent vascular repair in the development of
      cerebral vasospasm, we examined the effect of 2 synthetic serine protease
      inhibitors-FUT-175, an inhibitor of thrombin and the complement system, and
      argatroban, a selective inhibitor of thrombin-on the development of cerebral
      vasospasm in a rabbit SAH model. METHODS: One hundred Japanese White male rabbits
      were used in the study. The SAH was simulated by a single injection of autologous
      arterial blood into the cisterna magna. To evaluate the development of cerebral
      vasospasm, the caliber of the basilar artery was measured on x-ray film before
      and at 2 days after SAH. Nine groups of rabbits (n=6 each) were treated with
      continuous intravenous injection of FUT-175 (2.5, 5, 10, or 20 mg/d), argatroban
      (1.25, 2.5, or 5 mg/d), or the same amount of saline (vehicle) for 48 hours,
      starting 40 minutes after SAH. Two days after SAH, the expression of homodimer of
      platelet-derived growth factor-BB (PDGF-BB) in the basilar artery was examined
      with immunohistochemical techniques. In 20 normal rabbits, 5 microg of
      recombinant PDGF-BB or vehicle was injected into the cisterna magna, and the
      basilar arteries were examined on angiograms for 48 hours. RESULTS: Significant
      differences were observed in the caliber of the basilar arteries between the
      vehicle group and the groups with the 3 larger doses of FUT-175 (vehicle, 52+/
      5.0%; 5 mg, 79+/-5.7%; 10 mg, 80+/-2.5%; 20 mg, 80+/-3.7%) and between the
      vehicle group and the groups with the 2 larger doses of argatroban (vehicle, 52+/
      6.4%; 2.5 mg, 81+/-9.0%; 5 mg, 85+/-4.1%) (P<0.05). In the histological
      examination, administration of effective doses of FUT-175 or argatroban
      suppressed the expression of PDGF-BB in the endothelial and medial smooth muscle
      cell layers. Exogenous PDGF-BB caused delayed and prolonged vasoconstriction on
      normal basilar arteries. CONCLUSIONS: Activation of the serine protease cascade
      and/or thrombin after SAH was demonstrated to play an essential role in the
      development of cerebral vasospasm. The expression of PDGF-BB-like protein in the
      arterial walls correlated with the development of cerebral vasospasm. Elevated
      PDGF-BB level in the subarachnoid space was found to induce delayed and chronic
      vasoconstriction.

PMID- 11441218
TI  - Vitamin D deficiency and risk of hip fractures among disabled elderly stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Risk of hip fracture after stroke is 2 to 4 times that in
      a reference population. Osteomalacia is present in some patients with hip
      fractures in the absence of stroke, while disabled elderly stroke patients
      occasionally have severe deficiency in serum concentrations of 25-hydroxyvitamin
      D (25-OHD) (</=5 ng/mL). To determine the effects of vitamin D status on hip
      fracture risk, we prospectively studied a cohort of patients with hemiplegia
      after stroke who were aged at least 65 years. METHODS: We compared baseline serum
      indices of bone metabolism, bone mineral density, and hip fracture occurrence in
      stroke patients with serum 25-OHD </=25 nmol/L (</=10 ng/mL; deficient group,
      n=88) with findings in patients from the same cohort who had 25-OHD levels 26 to
      50 nmol/L (10 to 20 ng/mL; insufficient group, n=76) or >/=51 nmol/L (>/=21
      ng/mL; sufficient group, n=72). RESULTS: Over a 2-year follow-up interval, hip
      fractures on the paretic side occurred in 7 patients in the deficient group and 1
      patient in the insufficient group (P<0.05; hazard ratio=6.5), while no hip
      fractures occurred in the sufficient group. The 7 hip fracture patients in the
      deficient group had an osteomalacic 25-OHD level of <5 ng/mL. Higher age and
      severe immobilization were noted in the deficient group. Serum 25-OHD levels
      correlated positively with age, Barthel Index, and serum parathyroid hormone.
      CONCLUSIONS: Elderly disabled stroke patients with serum 25-OHD concentrations
      </=12 nmol/L (</=5 ng/mL) have an increased risk of hip fracture. Immobilization
      and advanced age cause severe 25-OHD deficiency and consequent reduction of BMD.

PMID- 11441219
TI  - Lipoprotein(a) and cognitive performances in an elderly white population: Cross
      sectional and follow-up data.
AB  - BACKGROUND AND PURPOSE: Elevated lipoprotein(a) [Lp(a)] serum levels have been
      associated with an increased risk of vascular diseases, and preliminary
      observations suggest that they are a risk factor for vascular dementia. The
      relationship between Lp(a) levels and cognitive performances in the general
      population has never been investigated. Our aim was to evaluate the effect of
      elevated Lp(a) levels on cognitive functions in the elderly. METHODS: Cognitive
      performances were assessed by means of the Mini-Mental State Examination (MMSE),
      the Babcock Short Story, and the Matrix Test in a population sample of 435 white
      subjects aged 65 to 84 years who were evaluated at baseline and after 3 years.
      Lp(a) levels were determined by ELISA. RESULTS: No statistically significant
      difference was found in neuropsychological test scores between subjects with and
      without elevated Lp(a) levels, although subjects with elevated Lp(a) levels had
      slightly better cognitive performances. This difference reached a statistical
      significance level only in a subscore of the Matrix Test (number of correct
      responses) when adjusted for age, sex, education, smoking, and history of stroke.
      At follow-up, no statistically significant difference was found in cognitive
      performances between subjects with and without elevated Lp(a) serum levels in
      either univariate or multivariate analyses. Subjects with and without elevated
      Lp(a) showed a similar decline rate during follow-up. CONCLUSIONS: In this sample
      of elderly white subjects, elevated Lp(a) levels were not associated with poorer
      cognitive performances or with an increased rate of cognitive decline. Elevated
      Lp(a) levels do not appear to be a major determinant of cognitive impairment in
      the elderly.

PMID- 11441220
TI  - A comparison of the costs and survival of hospital-admitted stroke patients
      across Europe.
AB  - BACKGROUND AND PURPOSE: Policy makers require evidence on the costs and outcomes
      of different ways of organizing stroke care. This study compared the costs and
      survival of different ways of providing stroke care. METHODS: Hospitalized stroke
      patients from 13 European centers were included, with demographic, case-mix, and
      resource use variables measured for each patient. Unit costs were collected and
      converted into US dollars using the purchasing power parity (PPP) index. Cox and
      linear regression analyses were used to compare survival and costs between the
      centers adjusting for case mix. RESULTS: A total of 1847 patients were included
      in the study. After case-mix adjustment, the mean predicted costs ranged from
      $466 [95% CI 181 to 751] in Riga (Latvia) to $8512 [7696 to 9328] in Copenhagen
      (Denmark), which reflected differences in unit costs, and resource use. The mean
      length of hospitalization ranged from 8.3 days in Menorca (Spain) to 36.8 days in
      Turku B (Finland). In the 3 Finnish centers at least 80% of patients were
      admitted to wards providing organized stroke care, which was not provided at the
      centers in Almada (Portugal), Menorca, or Riga. Patients in Turku A and Turku B
      were less likely to die than those in Riga, Warsaw (Poland), or Menorca. The
      adjusted hazard ratios were 0.18 [0.10 to 0.32] for Turku A, 0.18 [0.10 to 0.32]
      for Turku B, 0.68 [0.48 to 0.96] for Warsaw, and 0.56 [0.33 to 0.96] for Menorca,
      all compared with Riga. CONCLUSIONS: The cost of stroke care varies across Europe
      because of differences in unit costs, and resource use. Further research is
      needed to assess which ways of organizing stroke care are the most cost
      effective.

PMID- 11441221
TI  - Should stroke caregivers recognize the J wave (Osborn wave)?

PMID- 11441222
TI  - Addressing Healthy People 2010 objectives for stroke.

PMID- 11441223
TI  - Re: stroke and pregnancy.

PMID- 11441224
TI  - Heterogeneity of apparent diffusion coefficients within infarcts.

PMID- 11441225
TI  - Restricted dissociated sensory loss in lateral medullary infarction.

PMID- 11441226
TI  - Hypertension in acute stroke: what to do?

PMID- 11441227
TI  - Re: stroke severity determines body temperature in acute stroke.

PMID- 11441228
TI  - Adaptation to eccentric exercise: neutrophils and E-selectin during early
      recovery.
AB  - The purpose was to determine the responses of blood neutrophils and E-selectin
      concentrations during early recovery (<24hr) from 2 bouts of eccentric exercise.
      Subjects (N=9) completed 2 bouts of eccentric arm exercise using their non
      dominant arm (Bout 1 and Bout 2) and 1 non-exercise control condition. The
      exercise bouts were separated by 4 weeks, and the control condition preceded bout
      1. Neutrophil concentrations were significantly higher at 3, 6, and 9-hr post
      exercise for Bout 1 relative to Bout 2 and control. No significant changes in
      blood E-selectin concentrations were observed. Isometric strength deficit was
      similar for Bout 1 and Bout 2 at 5 min and 3 hr post exercise and was
      significantly great for Bout 1 relative to Bout 2 at 6, 9, and 24-hr post
      exercise. The adaptation to eccentric exercise is associated with a lower
      concentration of blood neutrophils during early recovery. The neutrophilia
      associated with novel eccentric arm exercise precedes secondary changes in
      isometric strength and is not associated with changes in the concentration of
      blood E-selectin.

PMID- 11441229
TI  - Meniscus and synovial membrane: an electronmicroscopic study on rabbits.
AB  - Seven healthy mature rabbits were used to study both the surface morphology of
      the meniscus using both transmission electronmicroscopy (TEM) and scanning
      electronmicroscopy (SEM) and articular cartilage of the femoral condyle using
      SEM. Results showed that the membrane covering the meniscus was structurally the
      extension of synovial membrane of the knee joint capsule. Additionally, the
      presence of canal-like openings over the membranes surface to the meniscus was
      noted, which were absent over the articular cartilage surface.

PMID- 11441230
TI  - Factors affecting force loss with prolonged stretching.
AB  - The purpose of this study was to investigate the factors underlying the force
      loss occurring after prolonged, static, passive stretching. Subjects were tested
      before and 5-10 min following 20 min of static, passive stretching of the
      quadriceps (N=12) or a similar period of no stretch (control, N=6). Measurements
      included isometric maximal voluntary contraction (MVC) force, surface integrated
      electromyographic (iEMG) activity of the quadriceps and hamstrings, evoked
      contractile properties (twitch and tetanic force), and quadriceps inactivation as
      measured by the interpolated twitch technique (ITT). Following stretching, there
      was a significant 12% decrement in MVC with no significant changes in the control
      group. Muscle inactivation as measured by the ITT and iEMG increased by 2.8% and
      20.2%, respectively. While twitch forces significantly decreased 11.7%, there was
      no change in tetanic force post-stretch. Although possible increases in muscle
      compliance affected twitch force, a lack of tetanic force change would suggest
      that post-stretch force decrements are more affected by muscle inactivation than
      changes in muscle elasticity.

PMID- 11441231
TI  - Contribution of visceral obesity to the insulin resistance syndrome.
AB  - A high visceral adipose tissue accumulation has been associated with many
      metabolic perturbations typical of the insulin resistance syndrome, such as
      dyslipidemia, impaired glucose-insulin homeostasis, hypertension and impaired
      fibrinolysis. It has been documented that male gender aging, and a hyperglycemic
      state are conditions that increase the likelihood of displaying features of the
      insulin resistance syndrome. Accordingly, studies have demonstrated that the
      variation in visceral adipose tissue accumulation explains a significant
      proportion of the gender differences in the metabolic risk profile. Age-related
      differences in metabolic components of the insulin resistance syndrome have also
      been shown to be partly explained by the concomitant increase in visceral adipose
      tissue accumulation found with age. Studies have suggested that a high visceral
      adipose tissue accumulation contributes significantly to the deterioration in the
      plasma lipid-lipoprotein profile found in hyperglycemic subjects. Finally, it
      appears that the clustering of metabolic alterations of the insulin resistance
      syndrome is more pronounced in obese subjects with high levels of visceral fat
      that in those with a lower visceral adipose tissue accumulation.

PMID- 11441232
TI  - Back fitness and back health assessment considerations for the Canadian Physical
      Activity, Fitness and Lifestyle Appraisal.
AB  - The Canadian Physical Activity, Fitness, and Lifestyle Appraisal (CPAFLA) is used
      as a measure for the health-related fitness of the general population. The CPAFLA
      includes an evaluation of back health, which is comprised of abdominal muscular
      endurance (partial curl-ups) and trunk flexion (sit and reach). This paper
      reviews the occupational, lifestyle, and physical risks associated with back pain
      and examines the measurement techniques used to assess health-related fitness
      components of back health in fitness assessments, such as the CPAFLA.
      Recommendations for future revisions of the CPACFLA's back health assessment and
      future research needs are presented.

PMID- 11441233
TI  - Sentinel Lymphadenectomy - Ready for Clinical Routine?

PMID- 11441234
TI  - Peptide Vaccination in Clinical Oncology.
AB  - Tumor-associated antigens recognized by cellular or humoral effectors of the
      immune system represent attractive targets for antigen-specific cancer therapy.
      Different groups of cancer-associated antigens have been identified inducing
      cytotoxic T-lymphocyte (CTL) responses in vitro and in vivo: 1) 'Cancer-Testis'
      (CT) antigens, which are expressed in different tumors and normal testis, 2)
      melanocyte differentiation antigens, 3) point mutations of normal genes, 4)
      antigens that are overexpressed in malignant tissues, and 5) viral antigens.
      Clinical studies with peptides derived from these antigens have been initiated to
      study the induction of specific CTL responses in vivo. Immunological and clinical
      parameters for the assessment of peptide-specific reactions have been defined, i.
      e., delayed-type hypersensitivity (DTH), CTL, autoimmune, and tumor regression
      responses. Early results show that tumor-associated peptides alone induce
      specific DTH and CTL responses and tumor regression after intradermal
      administration. GM-CSF was used as an adjuvant to enhance peptide-specific immune
      reactions by amplification of dermal peptide-presenting dendritic cells. Complete
      tumor regressions have been observed in the context of measurable peptide
      specific CTL. However, in single cases with disease progression after an initial
      tumor response, either a loss of the respective tumor antigen targeted by CTL or
      of the presenting MHC class I allele was detected, suggesting immunization
      induced immune escape. Based on these observations, cytokines to modify antigen
      and MHC class I expression in vivo are being tested to prevent immunoselection.
      Recently, a new CT antigen, NY-ESO-1, has been identified with a strategy
      utilizing spontaneous antibody responses to tumor-associated antigens (SEREX). NY
      ESO-1 is regarded as one of the most immunogenic antigens known today, inducing
      spontaneous immune responses in 50% of patients with NY-ESO-1-expressing cancers.
      Clinical studies with antigenic constructs to induce both humoral and cellular
      immune responses will show whether these are more effective for immunotherapy of
      cancer. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441235
TI  - Molecular Cytogenetics in Ewing Tumors: Diagnostic and Prognostic Information.
AB  - Ewing tumors (ETs) are characterized by rearrangements of the EWS gene located in
      22q12 and a high MIC2 expression. In 85% of ETs, the t(11;22)(q24;q12) generates
      chimeric fusion transcripts between the EWS and the FLI1 gene, whereas in the
      remaining cases the EWS gene is rearranged with different partners of the ETS
      oncogene family. Besides classical cytogenetic analysis, fluorescence in situ
      hybridization (FISH) and RT-PCR can be used to demonstrate these 22q12
      rearrangements which are pathognomonic for ETs. To visualize 22q12 rearrangements
      in individual cells, DNA probes flanking the EWS-R1 breakpoint region on
      chromosome 22 can be hybridized in double-target FISH experiments on tumor cell
      preparations. Intact chromosomes 22 are indicated by juxtaposition of the DNA
      probes, whereas rearrangements of the EWS gene separate the hybridization
      signals. In addition to 22q12 rearrangements, numerical aberrations of
      chromosomes 8 and 12 can be observed in about 50% of ETs, deletions at the short
      arm of chromosome 1 and der (16)t(1;16)(q12;q11.2) chromosomes in about 20% of
      the cases. Numerical aberrations, deletions at 1p36.3, and the t(1;16) were
      detected by using double-target FISH on touch, cytospin, and chromosome
      preparations, on frozen and paraffin sections and isolated deparaffinized nuclei.
      So far, numerical aberrations of chromosomes 8 and 12 did not show prognostic
      impact. However, deletions at 1p36.3 and imbalances between the long and short
      arms of chromosome 1 were associated with adverse clinical outcome in a group of
      patients with localized disease. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441236
TI  - Human DNA-Topoisomerases - Diagnostic and Therapeutic Implications for Cancer.
AB  - Topoisomerases constitute a family of highly conserved essential enzymes, which
      exist in all investigated living pro- and eukaryotic cells. They are
      indispensable for the control of DNA topology. Humans possess 4 types of
      topoisomerases, i. e. topoisomerase (topo) I, II, III and V. Topo I, a 100-kDa
      protein, is a member of the type-I enzyme group (type IB). Functionally, it is an
      ATP-independent DNA single-strand endonuclease and ligase that functions mainly
      during transcription but also during DNA replication. Topo II belongs to the type
      II enzymes and is represented in humans by 2 highly homologous isoforms, alpha
      (170 kDa) and beta (180 kDa). Contrary to topo I, the 2 topo II isoforms are ATP
      dependent double-strand endonucleases and ligases. Topo I and the beta-form of
      topo II are expressed in a proliferation-independent manner, whereas topo IIalpha
      is cell-cycle-regulated. Because of the crucial role of topoisomerases for the
      maintenance and replication of DNA during proliferation, cells become highly
      vulnerable when these functions are lost. Consequently, a wide range of drugs
      with cytostatic effects are topo inhibitors. Topo I inhibitors in clinical use
      belong to the camptothecin family, e. g. topotecan and irinotecan. Topo IIalpha
      inhibitors are constituents of most chemotherapeutic protocols and form a large
      heterogeneous group. It includes clinically used compounds such as the
      podophyllotoxin analogues etoposide and teniposide, the anthracyclines
      daunorubicin, doxorubicin and idarubicin, the anthracenedione mitoxantrone and
      amsacrine. Recently, substances with dual specificity that inhibit both topo I
      and topo IIalpha have been found. The clinical relevance of these new compounds
      remains to be established. Specific inhibitors of topo IIbeta have not been
      described yet. The majority of topo inhibitors interfere with the religation step
      in the normal action of the enzymes, which leads to a stabilisation of the so
      called cleavable complex. This results in DNA single-strand breaks in the case of
      topo I or double-strand breaks in the case of topo II. DNA single-strand breaks
      due to topo I inhibition are converted into double-strand breaks in the course of
      DNA replication. Such topo-mediated DNA strand breaks likely induce repair or
      apoptosis mechanisms via p53 and/or p21(WAF1/Clip1). As a consequence, while
      topoisomerases are required for proliferation, proliferation is also essential
      for efficacious topo inhibition. The cell-cycle-dependent expression of topo
      IIwas also successfully used for prognostic evaluations of survival in patients
      with cancer. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441237
TI  - Psychosocial Considerations about Spontaneous Remission of Cancer.
AB  - The existence of spontaneous remissions (SRs) in cancer disease has been proved
      by a considerable number of patients whose cancer disease has regressed without
      (adequate) treatment. In the moment, a lively discussion is going on about a
      number of explanations of SRs, which focus on psychological and psychosomatic
      theories and spiritual ideas. In order to broaden the empirical basis and in view
      of the fact that the psychosomatic approach seems to be very much in danger of
      speculations, an epidemiological register of these cases is necessary with the
      aid of which the data, including psychosocial variables, of all patients in
      question could be documented in a standardized manner. Whereas the fact of
      spontaneous remissions is generally denied, some people claim the occurrence of
      such remissions for themselves without justification. This phenomenon leads to
      the important question of the role of the personal analysis of a psychological
      theory in coping with the diagnosis of a malignant disease. Copyright 2000 S.
      Karger GmbH, Freiburg

PMID- 11441238
TI  - Preoperative Chemoradiation in Locally Advanced Pancreatic Carcinoma: A Phase II
      Study.
AB  - BACKGROUND: Effectiveness and feasibility of preoperative chemoradiation (CRT) in
      locally advanced adenocarcinoma of the pancreas are evaluated. MATERIAL AND
      METHODS: 29 eligible of 37 registered patients were treated. 3d-Conformal
      external radiotherapy was delivered with a 1.8-Gy single dose and a total dose of
      50.4 Gy plus 5.4 Gy boost. Simultaneous chemotherapy consisted of 5-fluorouracil
      and mitomycin C. RESULTS: Among 27 completely treated patients, 16 (59%)
      underwent surgery, 6 of them being irresectable intraoperatively. Ten patients
      (37%) had clear resection margins at Whipple's procedure. Eleven patients were
      not considered for surgery (7 still irresectable at restaging, 3 distant
      metastases, 1 refusal of surgery). Toxicity was predominantly hematological
      (grade 3: 30%, grade 4: 7%); furthermore, there was nausea/vomiting (grade 3:
      20%, grade 4: 0%). No patient died perioperatively. The tumor-related overall
      survival rate was better for resected patients than for nonresected patients (50%
      vs. 6%, 2-year survival, p = 0.07), median overall survival was 9 months (median
      follow-up, 28 months). CONCLUSIONS: Neoadjuvant CRT without significant acute
      toxicity produced a resectability rate of 37% (all R0), which should be confirmed
      by randomized phase III studies. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441239
TI  - Combination of Bolus 5-Fluorouracil, Folinic Acid and Mitomycin C in Advanced
      Gastric Cancer: Results of a Phase II Trial.
AB  - BACKGROUND: Gastric carcinoma still is a worldwide major cause of cancer death.
      Although various chemotherapy schedules yielded high response rates, median
      survival rarely exceeds 8-10 months. Many regimens are inevitably associated with
      significant toxicity which jeopardizes their value as palliative treatment,
      especially in patients with reduced performances status. Therefore, we initiated
      a phase II study for the treatment of advanced gastric carcinoma using a bolus
      regimen with mitomycin C (MMC), 5-fluorouracil (5-FU) and folinic acid (FA),
      allowing the enrollment of elderly patients or those with reduced performance
      status (WHO grade 2). PATIENTS AND METHODS: Between 1996 and 1998 we recruited a
      total of 58 patients with advanced gastric cancer to receive bolus MMC 3 mg/m(2),
      5-FU 450 mg/m(2), and FA 100 mg/m(2) on days 1-3. Treatment was repeated on day
      22. 53 patients met the inclusion criteria: male n = 36, female n =17; median age
      65 (range 26-81); mean WHO status 1 (range 0-2). RESULTS: Out of 53 patients 50
      were evaluable for response, all 58 patients who received therapy were evaluable
      for toxicity. Eleven patients (22%) achieved partial remission (95% CI: 11.5 
      36.0%), 24 (48%) no change and 15 (30%) were progressive. Median overall survival
      was 11.5 months, the median time to progression 6.0 months. Out of 290 treatment
      cycles the worst toxicities observed (WHO 2/3/4) were as follows: anemia 13/3/1,
      leukopenia 19/1/1, thrombopenia 11/3/0, nausea/emesis 11/2/0, infections 2/1/0,
      diarrhea 14/2/0, and stomatitis 6/1/1. One patient developed hemolytic-uremic
      syndrome. CONCLUSIONS: The tumor control rate (PR + NC) of 70% was comparable to
      established chemotherapy regimens, while median overall survival was promising.
      Toxicity was mild, allowing the treatment especially for elderly patients and on
      outpatient basis. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441240
TI  - Selection of CD34-Positive Blood Cells for Allogeneic Transplantation: Approaches
      to Optimize D34-Cell Recovery, Purity, Viability, and T-cell Depletion.
AB  - BACKGROUND: Methods for clinical-scale selection of CD34-positive hematopoietic
      stem and progenitor cells have facilitated allogeneic transplants using HLA
      mismatched healthy donors. We examined different approaches to purify mobilized
      CD34+ cells, focusing on yield, purity, and viability of the selected cells and T
      cell depletion levels. METHODS: Sixty-seven CD34-positive selections were
      performed for a total of 37 allogeneic transplantations, 23 of which from HLA
      haploidentical donors. The selection devices were the Isolex((R)) 300i (v. 1.12)
      used alone (n =13) or with the SuperMACS (n = 29); the CliniMACS (n = 3); and the
      Isolex 300i (v. 2.0b1). The latter was used for CD34-positive selection (n = 7)
      and combined CD34+/CD4 8 19-negative selections (n =15). DNAse was included to
      reduce cell clumping. RESULTS: With the Isolex 300i (v. 1.12), the median CD34+
      cell recovery increased from 51% (without DNAse) to 61% (15 mg DNAse) and 70%
      (7.5 mg). DNAse (5 mg) was used for 22 selections with the Isolex (v. 2.0b1)
      without cell clumping. CD34-positive cell purity, yield, and viability, as well
      as the degree of CD3 depletion varied with the selection device and procedure
      used. CONCLUSION: With regard to all of the above-mentioned parameters, the best
      results were obtained with the Isolex 300i (v. 2.0b1). Values achieved for CD34
      positive cells were 98% for purity, 50-60% for yield, and > 96% for cell
      viability; T-cell depletion was 4.5 to > 5 log. The automated and closed system
      provides target cells that are free of both magnetic particles and murine
      monoclonal antibody. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441241
TI  - Tumor-Infiltrating Lymphocytes Express Vascular Endothelial Growth Factor in
      Renal Cell Carcinomas.
AB  - BACKGROUND: Known influence of the immune system on metastases of renal cell
      cancer (RCC) has led to the development of several therapeutic approaches for
      further stimulation of the host immune system by cytokines and the retransfusion
      of tumor-infiltrating lymphocytes (TIL). Based on observations in human prostate
      adenocarcinomas and transitional cell carcinomas, we have investigated the
      presence of TIL in different stages of RCC in correlation to vascular endothelial
      growth factor (VEGF) expression as a parameter for tumor progression and adverse
      survival in RCC patients. METHODS: Samples from surgically obtained RCC (n = 28)
      and benign renal parenchyma (n =10) were snap-frozen and processed by double
      immunofluorescence staining with CD4/CD8 and VEGF antibodies. RESULTS: In 20 of
      28 RCCs a coexpression of TIL-specific markers CD4 and/or CD8 and VEGF was
      demonstrated. Control tissues were VEGF-negative and showed only negligible
      infiltration by CD4- or CD8-positive lymphocytes. CONCLUSION: The results
      indicate that at least 71% of TIL produce VEGF and may promote tumor progression
      rather than represent an abortive antitumor response of the host immune system.
      Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441242
TI  - Long-Term Clinical Remission in a Patient with Metastatic Gastric Cancer after
      Palliative Chemotherapy.
AB  - BACKGROUND: More than 50% of patients with gastric cancer initially present with
      locally advanced or metastatic disease. In general, gastric cancer in an advanced
      or metastatic stage is regarded as incurable. Despite treatment with palliative
      chemotherapy, the median survival time is still limited and does not exceed 12
      months. CASE REPORT: We report on a patient with advanced and metastatic gastric
      cancer who received palliative surgery and subsequent palliative chemotherapy.
      RESULTS: Complete remission occurred after R2 resection and palliative
      chemotherapy. The patient is now disease-free for 10 years after the end of
      chemotherapy. CONCLUSIONS: Palliative chemotherapy for metastatic gastric cancer
      may seldom lead to long-term clinical remission. Copyright 2000 S. Karger GmbH,
      Freiburg

PMID- 11441243
TI  - Extravasation of Oxaliplatin (Eloxatin((R))) - Clinical Course.
AB  - BACKGROUND: Up to now the cytostatic oxaliplatin was classified as nonvesicant.
      This is the first report on tissue necrosis induced by oxaliplatin extravasation
      in literature. A clinical course following oxaliplatin extravasation is reported.
      CASE REPORT: A 52-year-old white female with adenocarcinoma of the colon and
      hepatic and pulmonary metastases received palliative chemotherapy consisting of
      oxaliplatin, leucovorin, and 5-fluorouracil. By mistake oxaliplatin infusion
      extravasated subcutaneously in the left forearm; consequently, a painless red
      swelling occurred without any sign of further damage of the tissue. The infusion
      cannula was removed and oxaliplatin was infused into the right median cubital
      vein at the elbow. Again oxaliplatin extravasated subcutaneously. A severe
      painful necrotic reaction of the underlying flexor muscles of the right elbow
      developed, disabling the patient for 2 months, showing red-brown painful
      swelling, sclerosis of the skin, induration, fixation, and immobilization of the
      right elbow. Nonsteroidal analgesics and antibiotics were given, and lymphatic
      drainage and physiotherapy performed as generally accepted polypragmatic
      unspecific therapeutic procedure. After 2 months, the patient was able to bow and
      extend the right elbow except for an extension deficit of 20 degrees, pro- and
      supination became possible again, pain had completely resolved and strength
      recovered without limitation. Sclerosis of the skin and stiffness of the
      underlying tissue were slowly subsiding. CONCLUSION: Oxaliplatin can induce
      severe necrosis of underlying muscles by extravasation and therefore must be
      considered as a vesicant. Therefore oxaliplatin should be applied via a central
      venous access. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441244
TI  - Exacerbation of Wegener's Granulomatosis following Single Administration of
      Monoclonal Antibody 17-1A (Panorex((R))) during Adjuvant Immunotherapy of Colon
      Cancer.
AB  - BACKGROUND: Immunotherapy with monoclonal antibody 17-1A (mAb 17-1A) has been
      shown effective as an adjuvant treatment in UICC stage III colon carcinoma.
      Usually, severe side effects are infrequent with mAb 17-1A treatment. CASE
      REPORT: A 64-year-old man had a 18-month history of recurring arthralgia,
      sinusitis, and conjunctivits. After curative resection of UICC stage II colon
      cancer adjuvant treatment with mAb 17-1A was initiated. After the first
      administration (500 mg) the patient experienced an aggravation of the above
      mentioned symptoms which led to the diagnosis of Wegener's granulomatosis with
      multiorgan involvement. Under immunosuppressive therapy with cyclophosphamide and
      prednisone, clinical stabilization could be achieved. CONCLUSION: The
      exacerbation of Wegener's granulomatosis occurred immediately after the first
      administration of mAb 17-1A. This suggests that mAb 17-1A should be applied
      cautiously in autoimmune disease. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441245
TI  - Foundation of the German Society for Immunotherapy: Significant Advances in
      Cancer Treatment. Concerning Weissbach L.: Challenges of urological oncology for
      cure of cancer. Onkologie 2000;23:11-11.

PMID- 11441246
TI  - Author's Reply.

PMID- 11441248
TI  - Authors' Reply.

PMID- 11441247
TI  - Micrometastases and Microinvolvement in Esophageal Carcinoma. Concerning Feith et
      al.: Clinical relevance of lymph node micrometastases in esophageal carcinoma.
      Onkologie 2000;23:330-333.

PMID- 11441249
TI  - Therapy-Related Leukemia following High-Dose Chemotherapy: Compensating for the
      Benefit?

PMID- 11441250
TI  - Evaluation of Quality of Life in Oncology - Requirement or just an Option?

PMID- 11441251
TI  - ?
AB  - The major challenges in clinical oncological drug studies are to detect promising
      drug candidates early on in clinical drug development and to protect patients
      from adverse drug reactions of ineffective drugs. These challenges are met in the
      classical concept of clinical oncological drug trials in three phases. The aim of
      the present article is to provide a concise and comprehensive overview of the
      scientific logic of these 3 phases. Recent progress in the conception of clinical
      oncological drug studies was made in particular in phase I where the
      implementation of novel dose escalation procedures has led to a speeding up of
      phase I and an increase in the number of patients that receive an experimental
      drug in the therapeutic concentration range. However, the classical 3-phase
      concept of clinical oncological drug trials can not be transposed to trials with
      some novel anticancer drugs without critical reappraisal. It is therefore
      expected that this classical concept will undergo specific modifications in the
      near future. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441252
TI  - [Central European Society for Anticancer Drug Research]

PMID- 11441253
TI  - ?

PMID- 11441254
TI  - ?
AB  - The last years were characterized by efforts on the field of urological oncology:
      development of highly effective regimens for the curative treatment of metastatic
      diseases, improvement of diagnostic techniques based on monoclonal antibodies and
      molecularbiological techniques, development of operative techniques to improve
      quality of life in tumor patients. The cisplatin-based chemotherapy led to a
      dramatic improvement in patients with even extended testicular cancer disease and
      reflect one of the major highlights in urological oncology in the last century.
      Based on monoclonal antibodies and molecular techniques, diagnostic approach
      changed for prostatic carcinoma by using prostatic specific antigen (PSA) and for
      testicular cancer by determining alfa fetoprotein (AFP) and beta human
      choreongonadotropin (beta-HCG). These marker systems are of importance for
      treatment decision and follow up. Other efforts were revealed in the development
      of operative techniques with an improvement of quality of life (urinary bladder
      substitution, potency sparing operative techniques) and the possibility of organ
      preserving treatment in renal cell carcinoma. Copyright 2000 S. Karger GmbH,
      Freiburg

PMID- 11441255
TI  - Surgical Treatment of Breast Cancer - Current Status and New Concepts.

PMID- 11441256
TI  - The Monoclonal Antibodies Campath-1H and Rituximab in theTherapy of Chronic
      Lymphocytic Leukemia.
AB  - The treatment options for chronic lymphocytic leukemia (CLL) beside standard
      therapy with chlorambucil or other alkylating agents have dramatically increased
      in the last few years. Promising results have been reported with new cytotoxic
      agents such as the purine analogues fludarabine and 2-chlordeoxyadenosine, either
      at first diagnosis or at relapse. Nevertheless, all patients with CLL relapse
      after initial response. Since residual lymphoma cells are very likely to be the
      origin of the clinical relapse, there is a need for new therapeutic approaches
      with different mechanism of action to eliminate these residual cells. These
      approaches include allogeneic or autologous stem cell transplantation as well as
      immunotherapeutic strategies. Monoclonal antibodies, either alone or conjugated
      to toxins or radioisotopes, are thus being actively investigated. In clinical
      trials the genetically engineered chimeric unconjugated anti-CD20 antibody
      Rituximab and the humanized unconjugated anti-CD52 antibody Campath-1H achieved
      the most promising results in the treatment of patients with relapsed or
      refractory low-grade non-Hodgkin's lymphoma. Thus far there is only little
      clinical experience with Rituximab in patients with CLL, and the exact role of
      these agent in the treatment of CLL has still to be determined in ongoing and
      future trials. As a single agent Campath-1H showed more clinical activity in
      previously treated CLL patients than Rituximab, with response rates of up to 33%
      in a multicenter pivotal study. Furthermore, the potential risks of tumor lysis
      and anaphylaxia for both antibodies and immunosuppression particularly for
      Campath-1H must be taken into account. The present review will compare the
      development and the basic principles of these unconjugated monoclonal antibodies
      and consider their present and potential role in the treatment of patients with
      CLL. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441257
TI  - Oncology and Palliative Care.
AB  - Oncology developed as a discipline over the last decades. Treatment is
      concentrated on cure or palliation of the illness with the help of chemotherapy,
      radiotherapy or surgery. Palliative care has its origin in the hospice movement
      that started around 1960 in the UK. Centre of care is the patient and his family.
      Focus of care has moved from quantity to quality of life. Symptom control,
      communication, rehabilitation and care for the dying are main areas of palliative
      care. Palliative care and palliative medicine have only developed over the last
      10 years in Germany. It is still seen as care for the dying after completion of
      oncological treatment. The integration of palliative care in earlier stages of
      the disease is essential to offer a continuity of care for the patient and his
      family. Principles of palliative care need also be part of medical and post
      graduate training. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441258
TI  - Targeting Folates by Carboxypeptidase G2: Potential Applications in Anticancer
      Therapy.
AB  - Carboxypeptidase G2 (CPG2) cleaves folates and folate analogues resulting in
      alternative routes of folate metabolism. CPG2 is of particular interest in
      anticancer therapy for several reasons. CPG2 rapidly converts methotrexate (MTX)
      into less toxic metabolites causing a rapid decline of MTX serum levels in animal
      models as well as in humans. Thus, CPG2 is a powerful rescue agent in patients
      receiving high-dose MTX and might circumvent life-threatening toxicity in
      patients with MTX intoxication. As CPG2 causes a predefined and considerable
      decline of MTX levels, this substance might be also attractive for MTX dose
      escalation studies. In addition, CPG2 has been used in antibody-directed enzyme
      prodrug therapy. Prodrugs have been developed which are cleaved by CPG2,
      resulting in a release of active cytotoxic agents. The use of these prodrugs,
      attached to a tumor-specific antibody-CPG2- complex, might enhance concentrations
      of cytotoxic drugs in tumor tissues. Finally, CPG2 has been investigated in
      combination with trimetrexate, as it has been shown that trimetrexate is
      resistant to CPG2 cleavage. In conclusion, CPG2 is a novel drug with promising
      properties. However, clinical experiences are limited and further studies are
      necessary to define the role of CPG2 in cancer therapy. Copyright 2000 S. Karger
      GmbH, Freiburg

PMID- 11441259
TI  - Current Status of Dendritic Cell-Based Tumor Vaccination.
AB  - For several decades, approaches utilizing nonspecific immune stimulants have
      provided evidence that the immune system, when properly activated, may eradicate
      cancer cells. However, it was only after the identification of the first human
      tumor-associated antigen, less than a decade ago, that development of specific
      vaccination procedures for cancer patients became feasible. Recent insights into
      the pivotal role of dendritic cells (DCs) for initiation and regulation of immune
      responses have allowed the design of DC-based tumor vaccination trials. In
      addition, the development of methods to raise large numbers of DCs from
      peripheral blood monocytes has paved the way for their clinical application.
      Tumor-specific vaccination utilizing antigen-loaded autologous DCs, has become
      practical and applicable to patients and may lead to vigorous antitumor
      responses. This review outlines recent progress, obstacles still to be overcome,
      and the future potential of DC-based vaccination. Copyright 2000 S. Karger GmbH,
      Freiburg

PMID- 11441260
TI  - Recent Developments in Hematology and Transfusion Medicine.
AB  - Transfusion of allogeneic blood products carry a small but not negligible risk
      for the transmission of infections and may have immunosuppressive or immunogenic
      effects. The discovery, licensing, and clinical use of hematopoietic cytokines
      such as erythropoietin or thrombopoietin may reduce the requirements for
      allogeneic blood transfusions. However, the effectiveness has so far only been
      demonstrated in limited clinical situations. Further progress in avoiding
      allogeneic transfusions can be expected from the development of artificial blood
      cell substitutes. The potential and limits of these new techniques and substances
      to manage pancytopenia in cancer patients are reviewed briefly. Copyright 2000 S.
      Karger GmbH, Freiburg

PMID- 11441261
TI  - Attitudes and Beliefs towards Disease and Treatment in Patients with Advanced
      Cancer Using Anthroposophical Medicine.
AB  - BACKGROUND: In Switzerland, anthroposophical medicine has a long tradition,
      offers a special tumor treatment, is frequently used by cancer patients, and has
      been approved in 1998 by the Swiss government to be reimbursed by health
      insurances. This popularity contrasts with the fact that to date no sound
      evidence of the effectiveness of anthroposophical cancer treatments exists. In
      this study we draw a profile on a population of patients with advanced disease
      attending treatment at the anthroposophical Lukas Clinic (LC) regarding patients'
      attitudes, experiences and expectations. PATIENTS AND METHODS: All newly admitted
      patients with a diagnosis of locally advanced or metastasized breast,
      gastrointestinal, lung or gynecological cancer were recruited into a registration
      study. In parallel, a population of patients with the same inclusion criteria
      attending a conventional institution (Institute of Medical Oncology, University
      of Bern, IMO) was taken as a reference sample. Data were collected by means of a
      fully structured interview, and simple descriptive statistics was used for
      evaluation. RESULTS: 221 and 280 patients accrued at LC and at IMO, respectively.
      LC patients were mainly women (87%), had a good education (36% with completed
      college or university education), and were admitted on average 3.5 months after
      the diagnosis of advanced disease. With respect to their advanced cancer, they
      put very little hope in the effectiveness of conventional medicine, but expected
      great help from anthroposophical treatment. Compared with the reference
      population they cared more for psychological well-being and quality of life, but
      an important factor for choosing treatment at the LC was clearly the patients'
      strong belief in the effectiveness of anthroposophical treatment. CONCLUSIONS:
      With its holistic approach, anthroposophical medicine intends to provide tumor
      treatment together with supportive care throughout the course of the illness. To
      some patients this is an attractive alternative to conventional medicine, which
      too often focuses on tumor treatment only. Conventional medicine should clearly
      be advised to give higher priority to supportive care already early in the course
      of the disease. We acknowledge some patients' need for a more holistic approach,
      but anthroposophical medicine or any other providers of alternative or
      complementary cancer therapies should evaluate treatment effectiveness more
      thoroughly according to the principles of evidence-based medicine. Copyright 2000
      S. Karger GmbH, Freiburg

PMID- 11441262
TI  - Radiotherapy: Impact of Quality of Life and Need for Psychological Care: Results
      of a Longitudinal Study.
AB  - BACKGROUND: In the framework of a prospective longitudinal study, the quality of
      life (QoL) and support requirements of patients from a university hospital
      department of radiotherapy were evaluated for the first time by means of
      established psychodiagnostic questionnaires. PATIENTS AND METHODS: At first, 732
      patients were screened, of whom 446 (60.9%) fulfilled the criteria for inclusion;
      39.1% did not (refusals 21.0%, low Karnofsky performance status 6.6%, management
      problems 3.4%, language barriers 3.0%, cognitive restrictions 2.6%, death 2.5%).
      Disease-specific aspects of QoL (Functional Assessment of Cancer Treatment -
      General, FACT-G) and moderating variables [Social Support Scale (SSS), Disease
      Coping (FKV), Self-Assessment Depression Scale (SDS), and Self-Defined Care
      Requirements (BB)] were self-rated by patients with different tumor types before
      radiotherapy (T1), after radiotherapy (T2), and 6 weeks after the end of
      radiotherapy (T3). We studied 265 patients (157 male, 108 female; median age 58.6
      years) with complete data of three time points. RESULTS: In general, QoL of
      patients decreased significantly over all time points in all subscales. Social
      support was rated high and remained constant throughout the treatment. Apparent
      coping mechanisms were active problem-oriented coping, leisure activities, and
      self-support. The patients' depression proved to be an important and constant
      factor without significant changes. The support requirement is characterized by
      the need for more medical information and dialogue with a physician. CONCLUSIONS:
      Early specific support from personnel with radiotherapeutic skills, during the
      disease-coping process as well as during rehabilitation, should be a permanent
      component of an integrated radiooncological treatment schedule. Copyright 2000 S.
      Karger GmbH, Freiburg

PMID- 11441263
TI  - Radiotherapy of Choroidal Metastases in Patients with Disseminated Cancer.
AB  - BACKGROUND: Choroidal metastasis is the most common ocular tumor, in most cases
      related to breast and lung cancer. Radiotherapy (RT) mostly is the therapy of
      choice. However, there is a lack of data about the results of uniformly,
      prospective treated patients. PATIENTS AND METHODS: Between November 1994 and
      September 1997, 37 patients with 49 metastatic eyes were enrolled into the study.
      25 patients (68%) had unilateral and 12 patients (32%) had bilateral metastases.
      21 patients had breast cancer as primary tumor, 12 patients lung cancer, and 4
      patients other tumors. 3 patients were excluded from analysis, 34 patients with
      46 involved eyes were available for analysis. 29 of those patients had
      symptomatic metastases, 5 patients had asymptomatic choroidal metastases. RT was
      performed with bi- or unilateral asymmetric fields, total dose was 40 Gy with a
      single dose of 2 Gy, 5 fractions per week. 12 patients (35%) had a chemotherapy
      following RT due to diagnosis of general tumor progression. Endpoints of the
      study were visual acuity (VA), local tumor control, survival, and side effects.
      RESULTS: The median follow up was 6 months, 22 out of 34 patients died of
      metastatic disease. In 17 of symptomatic eyes (53%) an increase of VA and in 11
      of symptomatic eyes (34%) a 'no change' was achieved. The local tumor control
      rate after 18 months was 83%. One patient with asymptomatic metastasis (1/14
      eyes) developed symptoms until death. The median survival time was 15 months.
      Altogether, in 2 patients late side effects (6%) were observed (1 patients with
      bilateral retinopathy, 1 patient with optic nerve atrophy). CONCLUSIONS: RT with
      40 Gy is highly effective in the treatment of symptomatic and asymptomatic
      choroidal metastases, VA was stable or improved in almost 90% of treated eyes.
      The rate of side effects is low. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441264
TI  - Phase I Clinical Trial of a Day-1, -3, -5 Every 3 WeeksPhase I Clinical Trial of
      Day-1, -3, -5 Every 3 Weeks Schedule with Titanocene Dichloride (MKT 5) in
      Patients with Advanced Cancer. (Phase I Study Group of the AIO of the German
      Cancer Society).
AB  - BACKGROUND: Titanocene dichloride (TD) is an organometallic compound with
      antiproliferative properties in vitro and promising antitumor activity in
      preclinical in vivo models. The drug interferes with DNA, blocks the S/G(2) phase
      of the cell cycle and shows antiangiogenic properties. The purpose of this study
      was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity
      (DLT) of a 'split' dose administration schedule (days 1, 3, 5 q 3 weeks).
      PATIENTS AND METHOD: Patients with progressive advanced cancer and a creatinine
      clearance > 60 ml/min qualified for a treatment with TD after standard therapies
      (radio-, chemo-, hormone therapy) failed. A total of 10 patients (4 females, 6
      males) with a median age of 58 (range 49-68) years were treated with 80 mg/m(2)
      TD at days 1, 3 and 5 (repeated at day 22). The drug was administered as light
      protected infusion within 1 h. RESULTS: Significant side effects were as follows:
      nausea/vomiting, appetite loss, renal toxicity (elevation of serum creatinine and
      proteinuria) and liver toxicity (bilirubin and alkaline phosphatase elevation),
      but no myelosuppression. At the starting dose (3 x 80 = 240 mg/m(2) TD), renal (3
      patients) or liver toxicity (1 patient) of grade 3 was judged as DLT. No further
      dose escalation was possible. No objective tumor remission was observed.
      CONCLUSION: The tolerability of TD cannot be improved by splitting the total dose
      in to three treatments every other day. Compared to previous phase I data using a
      3-weekly and a 1-weekly schedule, the 'split' dose administration allowed no
      further increase of the total drug dose per treatment cycle. Thus, dose
      intensification by alterations of the application mode does not seem to be
      possible. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441265
TI  - Primary Intracranial Manifestation of CD7/CD56-Positive Acute Myelogenous
      Leukemia.
AB  - BACKGROUND: CD56 which is considered as a marker of natural killer cells is also
      expressed in some cases of acute myelogenous leukemia (AML) and is involved in
      cell adhesion mediating extramedullary leukemic infiltration. CD7/CD56
      coexpression has been suggested to be a distinct biological and clinical entity
      of AML. PATIENT: This is a report of a 53-year-old woman who developed CD7/CD56
      positive AML with primary manifestation as intracranial tumor. The patient
      reported of neurological impairment (impairment of visus and occurrence of double
      pictures). Cranial computed tomography showed an intracranial tumor, and
      histological examination exhibited myeloid blast cells. Peripheral leukocyte
      count at admission was within the normal range (5,32 Gpt/l), and percentage
      frequency of blasts in the blood smears was 54%. Cytological bone marrow
      examination showed diffuse infiltration by the same myeloid blast cells. The
      immunophenotype was CD7/CD13/CD33/CD38/CD56/ HLA-DR-positive. The blast cells
      were myeloperoxidase-positive but lactoferrin-negative. Thus, diagnosis of acute
      myeloid leukemia (M2 FAB) was established. Treatment consists of chemotherapy
      (Ara-C and anthracycline) and local radiation of the intracranial tumor. After
      treatment patient achieved a complete remission. CONCLUSION: With regard to the
      literature CD7/CD56-positive AML have a high incidence of central nervous system
      involvement which should be kept in mind and may be associated to CD56
      expression. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441266
TI  - Spontaneous Bleeding in a Patient with Malignant Lymphoma: A Case of Acquired
      Hemophilia.
AB  - BACKGROUND: Acquired hemophilia is a rare condition which can be associated with
      lymphoproliferative disease. CASE REPORT: Eleven years after the diagnosis of
      immunocytoma had been made, a 72-year-old man developed a high-titer factor VIII
      inhibitor. At this time, the lymphoma was without significant progress and there
      was no paraprotein in the serum. Partial thromboplastin time (PTT) was 83s,
      factor-VIII clotting activity was <1%, and inhibitor level was 50.4 Bethesda
      units. The patient presented with spontaneous hematomas in the skin and
      musculature of the extremities. Following combination chemotherapy with
      cyclophosphamide, vincristine and prednisolone (COP), there was a prompt
      disappearance of the inhibitor and normalization of coagulation; however, the
      patient developed serious infectious complications. When the inhibitor recurred
      he was treated with low-dose cyclophosphamide and prednisolone. This time there
      was a more delayed response, but the inhibitor disappeared again completely. Two
      months after cessation of therapy, there was again relapse. CONCLUSION: Causal
      relationship between lymphoma and acquired hemophilia remains speculative. At
      least in some cases of factor VIII inhibitors associated with malignant disease,
      immunosuppressive therapy may be sufficient to suppress the inhibitor. Copyright
      2000 S. Karger GmbH, Freiburg

PMID- 11441267
TI  - Clinical Implications of 3D-Conformal Radiotherapy.
AB  - INTRODUCTION: Local tumor control in cancer patients is the major goal of
      radiation therapy. More than 10% of cancer patients die as a result of local
      failure with no evidence of metastatic disease. A local failure can represent the
      cause of metastastic progression. As most malignant tumors show a steep dose
      response curve, an increased total dose may result in improved long-term cure
      rates at least in a subset of patients. But dose escalation is often not possible
      with conventional radiotherapy techniques because raising the dose to the target
      also raises the dose to surrounding normal tissue. Recent technical developments
      gave way to the introduction of 3-dimensional conformal radiation therapy (3DCRT)
      techniques into clinical practice. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441268
TI  - [Second-Line Therapy of Ovarian Carcinoma]
AB  - Despite the high response rate of ovarian cancer patients, 70% of them will
      relapse and have to be considered as candidates for second-line treatment. If the
      relapse is diagnosed within the first year after initial standard treatment with
      paclitaxel/carboplatinum, the tumor has to be classified as platinum-resistant
      disease with an expected response rate to second-line treatment between 10 and
      20% and a median survival time of about 12 months. The following drugs are used
      for second-line treatment: topotecan, gemcitabine, liposomal doxorubicine,
      vinorelbine, docetaxel, oral VP 16, oral treosulfane or hormones like tamoxifen,
      medroxyprogesteroneacetate, and GnRH analogues. Is the tumor relapse diagnosed
      later, re-treatment with the same first-line therapy achieves a response rate
      between 25 and 60%. If the tumor relapses again, only then second-line treatment
      as mentioned above will be given. If possible, radical surgical excision of the
      tumor is an additional useful treatment option. In addition to second-line
      treatment, palliation with analgesic drugs, puncture of pleural effusion or
      ascites with interferon instillation, palliative surgery of mechanical ileus,
      psycho-oncologic support, and substitution of tumor cachexia are of importance.
      Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441269
TI  - Improving the Quality of Reports of Meta-Analyses of Randomised Controlled
      Trials: The QUOROM Statement.
AB  - BACKGROUND: The Quality of Reporting of Meta-analyses (QUOROM) conference was
      convened to address standards for improving the quality of reporting of meta
      analyses of clinical randomised controlled trials (RCTs). METHODS: The QUOROM
      group consisted of 30 clinical epidemiologists, clinicians, statisticians,
      editors, and researchers. In conference, the group was asked to identify items
      they thought should be included in a checklist of standards. Whenever possible,
      checklist items were guided by research evidence suggesting that failure to
      adhere to the item proposed could lead to biased results. A modified Delphi
      technique was used in assessing candidate items. FINDINGS: The conference
      resulted in the QUOROM statement, a checklist, and a flow diagram. The checklist
      describes our preferred way to present the abstract, introduction, methods,
      results, and discussion sections of a report of a meta-analysis. It is organised
      into 21 headings and subheadings regarding searches, selection, validity
      assessment, data abstraction, study characteristics, and quantitative data
      synthesis, and in the results with <<trial flow>>, study characteristics, and
      quantitative data synthesis; research documentation was identified for eight of
      the 18 items. The flow diagram provides information about both the numbers of
      RCTs identified, included, and excluded and the reasons for exclusion of trials.
      INTERPRETATION: We hope this report will generate further thought about ways to
      improve the quality of reports of meta-analyses of RCTs and that interested
      readers, reviewers, researchers, and editors will use the QUOROM statement and
      generate ideas for its improvement. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441270
TI  - [Interdisciplinary onsensus on Diagnosis and Treatment of Testicular Germ Cell
      Tumors: Result of an Update-onference on Evidence-Based Medicine]
AB  - 1996 wurde von der <<Interdisziplinaren Arbeitsgruppe Hodentumoren>> (IAH), in
      der Vertreter an der Behandlung von Hodentumoren beteiligter Arbeitsgruppen der
      Deutschen Krebsgesellschaft (AIO, AUO und ARO) zusammenarbeiten, ein
      <<Interdisziplinarer Konsensus zur Diagnostik und Therapie von Hodentumoren>>
      erarbeitet und publiziert [1, 2]. 1998 erfolgte der Zusammenschluss der IAH mit
      der <<Organgruppe Hodentumoren>> der AUO zur <<German Testicular Cancer Study
      Group>> (GTCSG). Die Beteiligung aller wissenschaftlichen Fachgesellschaften, die
      mit der Klinik von Hodentumoren befasst sind, sollte die wissenschaftliche Basis
      erweitern, die Qualitat der von der Gruppe erarbeiteten diagnostischen und
      therapeutischen Standards fur Hodentumoren erhohen und eine breite Umsetzung der
      interdisziplinar erarbeiteten Empfehlungen zur Diagnostik und Therapie
      ermoglichen [3, 4]. Aufgrund von Anderungen der therapeutischen Standards, die in
      der Zwischenzeit erarbeitete wurden, ergab sich die Notwendigkeit, den Konsensus
      von 1996 zu aktualisieren. Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441271
TI  - [Milestones in Gynecological Oncology over the Last 20 Years]
AB  - In den letzten Jahrzehnten vollzog sich auch auf dem Gebiet der gynakologischen
      Onkologie ein grundlegender Wandel - dafur stehen Meilensteine. In der Natur der
      klinischen Medizin liegt jedoch, dass die fur die Entwicklung, Diagnostik und
      Therapie relevanten <<Meilensteine>> erst dann, wenn sie sich bewahrt und als
      dauerhaft erwiesen haben, als solche zu erkennen sind. Deshalb darf es nicht
      verwundern, dass sie auf dem Gebiet der gynakologischen Onkologie meist schon vor
      uber 20 Jahren gesetzt wurden. Obwohl es heute scheint, als seien zur Diagnose
      und Therapie gynakologischer Karzinome keine grundlegend neuen Gesichtspunkte und
      Techniken hinzugekommen, gab es in dieser Zeit gravierende Veranderungen.
      Copyright 2000 S. Karger GmbH, Freiburg

PMID- 11441273
TI  - Therapeutic vaccination against T-cell-defined tumor antigens.

PMID- 11441274
TI  - Assessment of quality of life in cancer patients: complexity, criticism,
      challenges.
AB  - Over the past two decades, quality of life (QoL) research has become an integral
      endpoint in clinical trials, yet, regarding its implementation in daily clinical
      work, much hesitation still abounds. This article discusses how complex
      psychological processes at work within a patient along with environmental factors
      act upon each other to form what is finally measured in a QoL score. An extended
      model of QoL is suggested which comprehensively describes the contribution of
      factors such as common psychological reactions to cancer, coping mechanisms,
      traits, and socioeconomic conditions to the final outcome in a QoL inventory. In
      order to avoid disappointment at the utility of results gained in QoL assessment
      both in clinical trials and daily routine, the choice of appropriate QoL
      instruments, their goal-directed implementation, and suitable expectations
      towards the anticipated aims are pivotal aspects to be ensured. Competent
      utilization of QoL assessment contributes to an enhanced standard of patient
      centered care in oncology.

PMID- 11441275
TI  - Value of neck dissection in patients with squamous cell carcinoma of unknown
      primary.
AB  - Lymph node metastases of cancer of an unknown primary (CUP syndrome) are
      responsible for 3-5% of the malignant diseases in the head and neck area. More
      than 70% of these patients show lymph node metastases of an unknown squamous cell
      carcinoma. The survival depends immediately on number and location of lymph node
      metastases. For a curative approach modified radical neck dissection combined
      with postoperative radiation therapy with or without chemotherapy should be
      considered in N1-N3 lymph node status. A radical neck dissection with
      postoperative radiation therapy should only be approved in cases of infiltration
      of the internal jugular vein, the accessory nerve and/or the sternocleidomastoid
      muscle. The different prognosis of patients with upper cervical and lower
      cervical lymph nodes should influence the indication and the extent of a neck
      dissection in the contralateral N0 neck.

PMID- 11441276
TI  - Targeted inhibition of telomerase in human cancer: will it be a double-edged
      sword?
AB  - More than 80% of human malignancies express telomerase activity, while normal
      somatic tissues in general lack it. During each normal cell division, there is a
      constant loss of DNA sequences at chromosomal ends, which is due to the 'end
      replication problem' of conventional DNA polymerase. Critical shortening of
      telomeres induces cell cycle arrest and eventually cell death. Telomerase, a
      ribonucleoprotein complex with a RNA (TR) and a catalytic subunit (TERT) as core
      components, is able to add reitineratedly telomeric repeat sequences to the very
      ends of chromosomes. It was suggested that activation of telomerase in tumor
      cells has a major impact on their continuous growth. Indeed, transfection of TERT
      constructs into various normal human cell types led to telomere elongation or
      stabilization and, most importantly, cellular immortalization. Conversely,
      inhibition of telomerase in tumor cell lines induced growth arrest, at least in
      first experimental settings. Such initial success implies that drug-mediated
      abrogation of telomerase action might be an ideal adjuvant treatment for cancer
      patients. There are, however, legitimate concerns about the generalization of
      such an approach.

PMID- 11441277
TI  - Current status of laparoscopic surgery in colorectal cancer.
AB  - Laparoscopic colorectal procedures offer several benefits postoperatively,
      including reduction of pain, minimal impairment of pulmonary and gastrointestinal
      function, and improved reconvalescence. At present, laparoscopic resections for
      colorectal cancer are discussed controversially due to oncologic radicality,
      potential tumor dissemination, and the fundamental problem of port-site
      metastases. Oncologic standards of open surgery for colorectal cancer are not
      compromised by the laparoscopic technique. Short-term results of both
      retrospective and prospective trials comparing open with laparoscopic surgery for
      colorectal cancer showed comparable oncologic outcomes related to recurrence and
      survival. Despite extensive research efforts, neither the incidence of port-site
      recurrence nor its causes have been clarified definitely. However, according to
      the preliminary results of recently published studies, the problem of port-site
      metastases may not be an inherited detriment of laparoscopic surgery, but rather
      an unfortunate sequel to the learning curve of the application of laparoscopic
      surgery in colorectal cancer. Finally, as long-term results of prospective
      randomized trials are still missing, the crucial issue whether laparoscopic
      resection for colorectal cancer is oncologically equivalent to open surgery,
      cannot be answered definitely. Therefore, in the interim, laparoscopic curative
      resections in colorectal cancer are only to be offered within prospective
      randomized trials.

PMID- 11441278
TI  - Clinical usefulness of free PSA in early detection of prostate cancer.
AB  - OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) is widely used as
      an aid in early detection of prostate cancer. Most patients with prostate cancer
      and a PSA level less than 10.0 ng/ml have early-stage disease. Thus, the
      detection of prostate cancer in its potentially curable stages requires the use
      of low PSA cutoffs, inevitably leading to many unnecessary biopsies. The combined
      use of free PSA and total PSA increases specificity of early detection. To
      develop risk assessment guidelines and a cutoff value of ratio of free (f) to
      total (t) PSA with a high predictive value for prostate cancer in men to whom the
      test would be applied in real life practice, a multicenter early detection trial
      was initiated. PATIENTS AND METHODS: In one week in November 1997, 963 urologists
      prospectively examined 11,644 men between 45 and 75 years by digital rectal
      examination (DRE) and prostate-specific antigen with 4.0 ng/ml as cutoff. Data of
      physical examination were collected by questionnaire. At this time participants
      were not aware of their PSA values. Suspicious findings were further investigated
      with sextant biopsy. Prostate volume was determined with transrectal ultrasound
      (TRUS). Different cutoff levels were correlated to age and detection rate.
      RESULTS: From1,115 biopsied men, the data of 633 men fulfilled the criteria DRE
      negative, TRUS-estimated volume, and PSA 4.0-10.0 ng/ml. In that cohort 91
      cancers were detected. Percentage of fPSA was significantly more predictive of
      cancer than tPSA (p < 0.001). The area under the ROC curve was 0.72 for percent
      fPSA (% fPSA) and 0.62 for total PSA. The cancer risk nearly doubled using a
      cutoff of 10% fPSA, the median %PSA level of the detected cancers. A better
      discrimination of cancer and noncancer especially in the age group above 70 years
      is possible. Using a cutoff of 16% fPSA increases positive predictive value (PPV)
      to 25% missing only 4% of cancers. Nearly 45% of the biopsies could be avoided.
      In the age group 45-69 years, a cutoff of 20% fPSA leads to PPV of 15%, missing
      6% of cancers. Unnecessary biopsies could be avoided in 12%. CONCLUSIONS: Using %
      fPSA in early detection of prostate cancer reduces the number of unnecessary
      biopsies, especially in men with negative rectal examination in the PSA range of
      4.0-10.0 ng/ml. In order to diminish biopsy rate in men 70 years or older a
      cutoff of 16% fPSA should be used. A cutoff of 20% fPSA in men younger than 70
      years is recommended to increase sensitivity in that age group.

PMID- 11441279
TI  - CUP (carcinoma of unknown primary) syndrome in head and neck: clinic, diagnostic,
      and therapy.
AB  - BACKGROUND: Up to 10% of all cervical lymph node metastases present without a
      known primary site. Between 70 and 80% of the found primary tumors are located in
      the head and neck region, because cervical lymph nodes represent the lymph
      drainage of the head and neck. PATIENTS AND METHODS: We demonstrate the clinic,
      diagnostic management and therapy of carcinoma of unknown primary (CUP) in this
      retrospective study of 75 patients who primarily presented cervical metastases
      with unknown primary tumor at the Otorhinolaryngological Department of the
      University of Leipzig, Germany. RESULTS: A primary tumor was found in 44% of the
      patients, and 76% of the primary tumors were localized in the head and neck
      region. The overall 5-year survival rate was 13.3%. The 34 patients with
      pretherapeutically detected primary tumors showed a tendency towards better
      survival, with a 5-year survival rate of 21% compared to 10% in patients with
      undetected primary. CONCLUSIONS: Following a thorough physical examination,
      radiologic imaging, i.e., computed tomography and/or magnetic resonance imaging,
      of the head and neck region as well a chest X ray, panendoscopy with biopsy of
      the most probable tumor sites, and diagnostic tonsillectomy should be performed.
      Further diagnostic procedures as gastroenterologic, urogenital and gynecological
      examinations should be performed, depending on histology and location of the node
      and under consideration of cost-benefit analysis. Curative treatment should at
      least include ipsilateral neck dissection and adjuvant irradiation of the
      complete cervical lymph drainage. In the literature, radiation of the
      laryngopharyngeal mucosa is still discussed controversially: some authors
      recommend the irradation of the pharyngeal mucosa extending from the nasopharynx
      to the upper esophagus, whereas others regard the resulting side effects as too
      high compared to the expected benefit.

PMID- 11441280
TI  - Improvement of skin care during radiotherapy.
AB  - BACKGROUND: State-of-the-art radiotherapy, new insights into pharmacology and
      novel operating techniques require patient-oriented adaptation of care. PATIENTS
      AND METHOD: At the Radio-oncology Department of the Kaiser Franz Josef Spital,
      Vienna, a new skin care concept for patients undergoing radiotherapy was
      introduced in March 1999. This concept has subsequently been applied in all cases
      regardless of the diagnosis prompting referral (79 ENT, 305 breast, 134 prostate,
      89 colorectal cancer and 751 other patients). Radiotherapy consisted of photon
      and/or electron radiation on the linear accelerator. The energy ranges were
      between 6 and 15 MV for photon therapy and between 6 and 12 MeV for electron
      radiation. Patients received an average total radiation dose of 50-66 Gy at
      single fractional doses of 1.8-2 Gy 5 times a week. Powdering of the skin was
      replaced by a moist skin care program. Patients were allowed to take cool whole
      body showers without soap, including the irradiated skin areas, 3 times a week.
      RESULTS: With the new skin care program dryness of the skin and resultant
      allergic skin reactions became less common. Broken skin an epitheliolysis were
      clearly reduced and superinfections were prevented. CONCLUSION: Moist care of
      irradiated skin areas during radiotherapy thus improved radiation tolerance and
      patient acceptance.

PMID- 11441281
TI  - The treatment of primary urethral carcinoma--the dilemmas of a rare condition:
      experience with partial urethrectomy and adjuvant chemotherapy.
AB  - BACKGROUND: Primary urethral carcinoma is a very rare condition, and no large
      scale experience with such cases has been published. Treatment will therefore
      have to follow rules established for the treatment of similar conditions.
      PATIENTS: Six cases of primary urethral carcinoma (5 male, 1 female) who had been
      treated at our institution between 1995 and 1999 were retrospectively analyzed.
      In 3 male cases, a primary urothelial carcinoma of the distal urethra was treated
      by distal urethrectomy only. In 3 other cases with locally advanced tumors and/or
      lymph node metastases surgical treatment was followed by adjuvant cisplatinum
      containing chemotherapy. RESULTS: In the 3 cases with distal urethral carcinoma,
      partial urethrectomy with preservation of the penis resulted in cure, with a
      follow-up of 12-71 months. In the cases with advanced disease, adjuvant
      chemotherapy after surgery has resulted in complete remissions in all 3 cases,
      with a follow-up of 4-47 months at present. CONCLUSIONS: In localized,
      noninvasive carcinoma of the distal male urethra, partial urethrectomy seems
      adequate and the avoidance of penile amputation justified. In advanced cases,
      after local excision and lymphadenectomy adjuvant chemotherapy which by necessity
      must follow the guidelines established for the treatment of other urothelial or
      squamous cell malignancies seems to be beneficial.

PMID- 11441282
TI  - Posttreatment histology and microcirculation status of osteogenic sarcoma after a
      neoadjuvant chemo- and radiotherapy in combination with local electromagnetic
      hyperthermia.
AB  - BACKGROUND: Many biological attributes of tumors (including regional blood flow
      and microcirculation) can deteriorate the homogeneity of heat distribution and
      temperature elevation during hyperthermia. We analyzed the connection between the
      microcirculation status of osteogenic sarcomas and the posttreatment histology
      after neoadjuvant chemotherapy, irradiation and local hyperthermia. PATIENTS AND
      METHODS: 62 patients with histologically verified osteosarcoma (35 men, 27 women,
      age 9-53, average 21 years) were enrolled in the retrospective pathohistological
      study. 61 patients were evaluable. In 72.6% of cases the tumor was localized in
      bones forming knee joints. All patients received neoadjuvant treatment [6
      hyperthermias (60 min, 42-45 degrees C), daunorubicin 30-50 mg/m(2), 6 infusions,
      adriamycin or cisplatin 30 mg/m(2) for 3 days or once 90 mg/m(2) monochemotherapy
      before the hyperthermic procedure; subsequently gamma-therapy, 20-36 Gy] followed
      by surgery. From archives, a control group was formed of 20 therapy-naive tumors.
      Resected tumors were histologically examined for assessment of spontaneous and
      therapeutically induced alterations. For analysis of the functionality status of
      microcirculation on histological cuts, 40 tumors (without selection) were
      investigated: 10 controls and 10 cases each with minimal, subtotal and total
      posttreatment alterations. RESULTS: Chemotherapy and radiotherapy in combination
      with local hyperthermia induced a distinct damage to osteosarcoma. In 39.3 and
      35.7% of cases there was subtotal and total devitalization of tumor parenchyma,
      respectively. Thrombosis of magistral and middle vessels, stasis in the
      microcirculation tree (collapse), damage to intimal vessels and endothelial
      cells, and necrotic alterations of the vessel walls appeared predominantly in
      central areas of tumors. Tumors with minimal devitalization of the parenchyma had
      a share of nonfunctional vessels ranging from 10.6 to 61.7%, mean 29.7%. In
      tumors with subtotal necrosis, between 34.5 and 72.0% (mean 49.46%) of vessels
      were nonfunctional (stasis, thrombosis). In 10 cases with 100% necrosis of the
      osteosarcoma parenchyma, a mean of 56.05% of nonfunctional vessels was registered
      (12.3-83.0%). In the control group, between 2.85 and 73.4% (mean 21.69%) of
      vessels showed damage to the microcirculation. CONCLUSION: There is a direct
      correlation between deterioration of the microcirculation in osteosarcoma and
      thermo-radiochemotherapy- induced tissue alteration; the devitalization grade is
      directly proportional to the number of nonfunctional vessels in the tumor.

PMID- 11441283
TI  - Contribution of comparative genomic hybridization and fluorescence in situ
      hybridization to the detection of chromosomal abnormalities in B-cell chronic
      lymphocytic leukemia.
AB  - BACKGROUND: B-chronic lymphocytic leukemia (B-CLL), the most common type of
      leukemia in Western Europe and the United States, is characterized by clonal
      chromosomal abnormalities detected in almost half of the studied patients. The
      precise determination of chromosomal changes helps to indicate the prognosis and
      to understand the pathogenesis of CLL. METHODS AND PATIENTS: We applied
      conventional cytogenetics (CC), FISH and comparative genomic hybridization (CGH)
      to the investigation of clonal abnormalities in 88 B-CLL patients at the time of
      diagnosis. RESULTS: By using CC of bone marrow cells without any stimulation, non
      random chromosomal changes were found in 17 (19%) of 88 patients. The employment
      of FISH and CGH revealed chromosomal changes in additional 33 patients, thus
      increasing the detection rate of chromosomal abnormalities to 57%. The most
      common abnormalities detected in our patients included deletions of 13q in 16
      cases (18%), followed by trisomy of chromosome 12 in 12 patients (13%), deletions
      of 11q in 10 patients (11%) and deletions of 17p in 10 patients (11%). A
      statistically significant correlation between higher disease activity and the
      presence of deletions 11q and 17p was observed. CONCLUSION: The addition of FISH
      and CGH to CC in 88 B-CLL patients improved the detection of clonal chromosomal
      changes from 19 to 57%. The most frequent chromosomal change was deletion of
      13q14 (18%). Deletions of 11q23 and 17p13 were found in patients with higher
      clinical disease activity. Our results underline the importance of employing FISH
      and CGH techniques in CLL patients. CC without any stimulation has a low
      detection rate and is not suggested for detection of chromosomal changes in CLL.

PMID- 11441284
TI  - Malignant glioma as a secondary malignant neoplasm after radiation therapy for
      craniopharyngioma: report of a case and review of reported cases.
AB  - BACKGROUND: The development of a secondary neoplasm in childhood cancer survivors
      attains growing importance due to the reported excellent survival and therefore
      the long exposure to potentially carcinogenic effects of treatment. CASE REPORT:
      We report a 14-year-old girl in whom a large craniopharyngioma (CP) was
      diagnosed. After surgery, radiation therapy (RT) was given for residual tumour.
      Discrete progression necessitated further surgery, resulting in permanent tumour
      control. Soon after the second surgery hypothalamic-pituitary dysfunction
      developed together with obesity. Supportive hormone therapy was initiated. Growth
      hormone (GH) therapy was also given for 15 months. Four years after the
      diagnosis, a cerebropontine anaplastic astrocytoma WHO grade III was detected,
      with the main lesion being at the dorsal edge of the irradiated area. The girl
      died 1 month later from this secondary presumably radiation-induced tumour. Only
      recently a second child with RT for a CP was diagnosed with malignant glioma in
      our hospital. CASE REPORTS IN THE LITERATURE: 12 other cases of malignant glioma
      have been reported after RT for CP. Including our present cases, the mean latency
      period was 10.7 years (median 9.6 years). However, the shortest latency periods
      were found in patients who had received GH therapy. In numerous cases, the
      secondary tumour was seen at the edge of the irradiated volume, and not in the
      region with the highest absorbed dose. CONCLUSIONS: Therapy-induced secondary
      gliomas after treatment of CP or other intracranial tumours are rare but dramatic
      late events with a very poor prognosis. Including our own 2 patients, we reviewed
      14 cases of CP with occurrence of a secondary, probably radiation-induced
      malignant glioma. The short latency periods for patients treated with GH is
      remarkable. We therefore suspect that GH therapy may accelerate the development
      of a secondary brain tumour. We are reluctant to recommend GH therapy in
      conventionally irradiated CP patients. In order to seriously answer the questions
      about therapy-induced secondary neoplasms, a life-long follow-up is mandatory for
      all patients who are survivors of childhood cancer.

PMID- 11441285
TI  - Giant malignant mesenchymoma of the spermatic cord with bidirectional
      differentiation.
AB  - BACKGROUND: Spermatic cord neoplasms are a rare tumor entity and, moreover, of
      benign behavior. Malignant tumors of the spermatic cord are mostly of mesenchymal
      origin. We present the unusual case of a giant malignant mesenchymoma of the
      spermatic cord with bidirectional differentiation into a liposarcoma and a
      leiomyosarcoma. CASE REPORT: A 84-year-old male patient presented with a scrotal
      mass on the left side which was observed growing since 1 year and misdiagnosed as
      scrotal hernia or testicular hydrocele. Ultrasound and computed tomography
      demonstrated a solid tumor suggesting a spermatic cord tumor. The patient
      underwent hemiscrotectomy, and the histological examination of the 2,500-gram
      specimen revealed a malignant mesenchymoma originating from the spermatic cord
      with two distinct histopathological compartments of liposarcoma and
      leiomyosarcoma. Because an adjuvant therapy protocol is of questionable effect
      and because of the patient's age no further therapy was applied. The patient was
      closely followed and is now, 5 years after surgery, still free of disease.
      CONCLUSION: Even in older patients, scrotal masses should be considered malignant
      tumors as long as no benign diagnosis has been proven. Although malignant
      mesenchymomas are rare tumors with poor prognosis, in selected cases even large
      tumor masses, as presented, can be cured by surgery.

PMID- 11441286
TI  - [TNM system and modern diagnostic imaging].

PMID- 11441287
TI  - [Recommendations of the Working Group 'Supportive Massnahmen in der Onkologie'
      concerning the Clinical Use of Cytoprotectives].

PMID- 11441288
TI  - [Chemotherapy of colorectal cancer--which therapy is justified for elderly
      patients?].
AB  - Treating elderly patients with colorectal cancer is a challenging task for which
      many aspects have to be taken into account. 70% of patients with colorectal
      cancer are 65 years or older and the number of elderly patients is expected to
      increase. As elderly patients frequently exhibit adverse physical or socio
      economic conditions, a thorough geriatric assessment of the patient's suitability
      for therapy is essential before making a decision. At present, adjuvant 5-FU
      based chemotherapy (in colon cancer) and adjuvant radio-chemotherapy (in rectal
      cancer) in the elderly is recommended for locally advanced or node positive tumor
      after tumor resection, since the benefit may be comparable to that achieved in
      younger patients. There is enough data to support the use of 5-FU based
      chemotherapy in elderly patients in the palliative setting. New substances have
      recently been added to the armentarium for metastatic colorectal cancer. However,
      there is as yet not sufficient data to guide the use of these new drugs (such as
      oxaliplatin or irinotecan) in elderly patients. However, first clinical studies
      seem to indicate a comparable efficacy and toxicity in elderly patients to that
      observed in younger patients. Further clinical trials of chemotherapy in elderly
      patients with colorectal cancer are necessary to gain information about treatment
      recommendations.

PMID- 11441289
TI  - Neoadjuvant and adjuvant chemotherapy of locally advanced stomach cancer.
AB  - Surgical treatment of locally advanced gastric carcinoma still results in
      unsatisfactory survival results. The addition of adjuvant chemotherapy has been
      shown to be of little value and is not considered standard practice. Preoperative
      chemotherapy, however, has a strong theoretical basis and may achieve significant
      tumor shrinkage and downstaging and thus allow complete resection of cancers
      previously judged by the responsible surgeon to be inoperable. However, it has
      not yet been demonstrated whether preoperative chemotherapy prolongs the survival
      of patients with potentially resectable cancers. Based on theoretical reasons,
      preoperative chemotherapy may be expected to be more efficient than postoperative
      chemotherapy. Various phase II trials have shown the feasibility of this
      approach, and encouraging results were found. Differing diagnostic methods,
      inclusion criteria, and chemotherapy regimens hamper direct comparisons between
      the trials. Several useful new drugs including taxanes and camptothecins and
      promising chemotherapy regimens incorporating continuously infused 5-fluorouracil
      have been introduced recently. Ongoing large randomized clinical trials (MAGIC
      trial, EORTC, SAKK) currently study the efficacy of preoperative chemotherapy in
      locally advanced gastric carcinoma.

PMID- 11441290
TI  - Urologic approaches to metastatic renal cell carcinoma.
AB  - The treatment of choice for nondisseminated disease is surgery. However, the 5
      year survival rates for all stages do not exceed 60%, even in contemporary
      series. Further improvement will most likely have to await the development of a
      more effective systemic therapy and the application of combined treatment
      modalities to counter the relatively high number of patients presenting with
      advanced stages. Treatment options in metastatic disease include nephrectomy
      alone, sometimes in combination with metastasectomy in selected cases, or
      cytoreductive surgery followed by immunotherapy. Alternatively, one may apply
      immunotherapy initially and perform adjuvant nephrectomy in the case of a
      response, or proceed with immunotherapy as a monotherapy. Nevertheless, long-term
      survival rates range merely from 5 to 10%, depending strongly on patient
      selection criteria. Concepts and progress in this field appear to be of major
      interest for modern urooncologists following the advent of immunotherapeutic
      strategies that require a surgical intervention at some stage of the treatment
      cascade.

PMID- 11441291
TI  - Will analogs of 1,25-dihydroxyvitamin D(3) (calcitriol) open a new era in cancer
      therapy?
AB  - Numerous in vitro and in vivo observations, demonstrating that 1,25
      dihydroxyvitamin D(3) is a potent inhibitor of tumor cell growth, provided the
      rationale for using this seco-steroid hormone to treat patients with leukemia and
      various types of cancer. However, the therapeutic efficacy of systemically
      applied vitamin D analogs for treating cancer has not yet fulfilled its promise.
      A main reason for these disappointing results is that the use of systemically
      applied vitamin D analogs is limited by severe side effects, mostly
      hypercalcemia, at the supraphysiological doses needed to reach clinical
      improvement. New concepts for the development of cancer treatment strategies that
      are based on the use of vitamin D(3) compounds are discussed in this manuscript.
      At the moment, different strategies that may enable the application of vitamin D
      analogs for the treatment of various malignancies, including malignant skin
      tumors, are employed. It has been shown that certain vitamin D analogs differ in
      their intracellular metabolism, nongenomic actions, pharmacokinetics, interaction
      with the vitamin D binding protein (DBP) or the vitamin D receptor (VDR). Several
      of these new concepts are based on recent laboratory results demonstrating that
      VDR requires heterodimerisation with additional nuclear cofactors such as the
      retinoid-X receptor (RXR) for sufficient DNA-binding or are based on new findings
      in the metabolism of vitamin D. Taken together, these new strategies hold promise
      that analogs of 1,25-dihydroxyvitamin D(3) may herald a new era in the treatment
      of various malignancies, including skin cancer.

PMID- 11441292
TI  - External radiotherapy of thyroid cancer.
AB  - Differentiated thyroid cancer comprises papillary, mixed papillary-follicular and
      follicular adenocarcinomas. They are mostly hormone-sensitive and respond to
      thyroid-stimulating hormone (TSH) suppression. The standard treatment is total
      thyroidectomy, (131)I therapy and thyroid hormone suppression therapy. Adjuvant
      external radiotherapy is discussed controversially. Most authors recommend
      adjuvant external radiotherapy for extra-capsular tumor extension. Decision on an
      individual basis should be made for patients with lymph node involvement. In the
      case of incomplete surgical resection, external radiotherapy should be applied if
      second surgery is not possible. For medullary thyroid cancer, external beam
      radiotherapy seems to be beneficial for patients with surgically inaccessible
      disease, with microscopic residual or gross tumor after surgery, with recurrent
      locoregional disease, or with surgically unmanageable metastases. Patients
      suffering from anaplastic thyroid cancer should receive combined treatment
      consisting of extensive surgery, external irradiation with total doses up to 60
      Gy, and chemotherapy. The combined treatment modality leads to higher local
      control rates and prolongs survival.

PMID- 11441293
TI  - Etiologic factors in soft tissue sarcomas.
AB  - Soft tissue sarcomas account for about 1% of all malignancies. The increase in
      incidence of soft tissue sarcomas during the recent decades may predominantly be
      attributed to AIDS-related Kaposi's sarcoma; when this tumor is excluded,
      conclusive evidence for an age-adjusted increase is lacking. Beside the well
      investigated role of the human immunodeficiency virus 1 (HIV-1) and the human
      herpesvirus 8 (HHV-8) in the tumorigenesis of AIDS-related Kaposi's sarcoma and
      several inherited disorders, considerable evidence support a relationship between
      occupational chemicals as vinyl chloride, phenoxyacetic acid herbicides,
      chlorphenols, dioxin, medicinal measures as Thorotrast exposure and therapeutic
      irradiation, and the development of soft tissue sarcoma. Hormones and chronic
      repair processes are further probably sarcoma-promoting factors. Considering the
      rarity of soft tissue sarcomas despite the vast portion that soft tissues
      comprise in the human body, additional knowledge on the tumorigenesis of soft
      tissue sarcomas might considerably contribute to the understanding of the
      etiologic pathways of malignant tumors in humans.

PMID- 11441294
TI  - Molecular markers in testicular germ cell tumors--objects of clinical research or
      close to becoming clinical tools?
AB  - The aim of this short review is to critically evaluate hitherto investigated
      molecular markers for testicular germ cell tumors. Molecular parameters have been
      clinically established as diagnostic and prognostic markers for a number of
      tumors; this has not yet been achieved for germ cell tumors. There are
      interesting prospects, however. Studies on the ribonucleoprotein telomerase, for
      example, have demonstrated a correlation between enzyme activity and
      chemotherapeutic drug sensitivity. Moreover, innovative treatment approaches
      target this reverse transcriptase via telomerase antisense RNA. Another potential
      diagnostic marker is the detection of circulating tumor cells, which correlated
      with an increased relapse rate in initial studies. There are also interesting
      possibilities for the germ-cell-tumor-specific isochromosome [i(12)p], which is
      helpful in the differential diagnosis of mediastinal masses. Here initial studies
      demonstrated a correlation between the copy number and resistance against
      chemotherapeutic drugs. Without prospective studies to validate data obtained
      thus far, neither these nor other parameters can be assessed as diagnostic and
      prognostic factors. Irrespective of their immediate clinical applicability,
      however, investigations on molecular alterations in testicular germ cell tumors
      will become the basis for a molecular-diagnostically oriented subclassification
      of tumors as well as for novel therapeutic approaches.

PMID- 11441295
TI  - Endobronchial ultrasound (EBUS)--assessment of a new diagnostic tool in
      bronchoscopy for staging of lung cancer.
AB  - BACKGROUND AND OBJECTIVE: Conventional imaging procedures proved to be
      insufficient for staging of lung cancer, especially with respect to N-stage,
      infiltration of mediastinal structures, and early lung cancer. As also the view
      of the endoscopist is restricted, we developed the new method of endobronchial
      ultrasonography (EBUS) as an adjunct to conventional bronchoscopy. The initial
      technical problems were solved by development of a balloon catheter for
      application of miniaturized 20-MHz probes. PATIENTS AND METHODS: Between January
      and December, 1999 all patients with an indication for bronchoscopy and
      additional EBUS were documented prospectively. RESULTS: In 648 patients we used
      additional EBUS. Of these, 242 (37%) were female and 406 (63%) were male. The
      mean age was 49.2 (range 0-83) years. The mean procedure time for the
      bronchoscopies was 18.9 (range 5.7-38.9) min, and the mean time for EBUS was 6.3
      (range 3.1-14.4) min. Side effects were comparatively rare. 34 patients (5%)
      needed supplementary oxygen during the examination, the others tolerated EBUS
      without any desaturation. CONCLUSION: EBUS is a new technology that can be easily
      applied and is well tolerated. It improves the results of bronchoscopy in
      addition to conventional diagnostic procedures. Further developments will be made
      in future to improve the application of ultrasound in chest medicine.

PMID- 11441296
TI  - The phenotype of ascitic fluid lymphocytes in patients with ovarian carcinoma and
      other primaries.
AB  - BACKGROUND: Ascitic tumor-infiltrating lymphocytes (TIL) are a potential source
      of effectors for adoptive immunotherapy. PATIENTS AND METHODS: The TIL phenotype
      was examined by two-color flow cytometry in malignancy-related ascites of 49
      patients with different primaries. Interleukin-10 (IL-10) and neopterin were
      determined in ascitic fluid by enzyme-linked immunoassay. RESULTS: Malignant
      melanoma patients had significantly higher CD3(+), CD3(+)CD8(+) and
      CD3(+)CD95(+), and lower CD3(+)CD4(+) lymphocyte numbers than patients with other
      primaries. Ovarian cancer patients had higher CD3(+)CD45RO(+), CD8(+)CD28(+),
      CD19(+)CD86(+), CD19(+) and CD19(+)CD86(+) lymphocyte numbers, and lower NK cell
      numbers than patients with gastrointestinal and pancreatic primaries. Pretreated
      patients had significantly lower concentrations of IL-10, lower CD8(+)CD28(+),
      CD3(+)CD45RA(+), and higher CD3(+)CD80(+) numbers than chemotherapy-naive
      patients. Patients with hepatic metastases had lower CD3(+), CD3(+)CD4(+) and
      CD3(+)CD45RO(+), and higher CD3(+)CD25(+) and NK cell numbers than patients
      without liver metastases. A substantial number of cells exhibited dendritic cell
      phenotype. Significant correlations were observed between neopterin and IL-10
      concentrations, and numbers of CD8(+)CD28(+) and CD3(+)CD80(+) lymphocytes.
      CONCLUSIONS: Some parameters of TIL phenotype differ depending on primary,
      previous treatment, or the presence of liver metastases. A negative correlation
      was observed between IL-10 and neopterin, and an opposing effect of local
      concentrations of IL-10 and neopterin on the numbers of CD8(+)CD28(+) and
      CD3(+)CD80(+) was noted.

PMID- 11441297
TI  - Treatment of aggressive, or progressing indolent peripheral T- and NK-cell
      neoplasias by combination of fludarabine, cyclophosphamide and doxorubicine.
AB  - BACKGROUND: Regarding standardization of treatment, classification, and
      pathophysiology of peripheral T- and NK-cell neoplasias the current knowledge is
      markedly behind that of B-cell lymphomas, which are approximately 10 times more
      frequent. In May 2000, the study group 'Peripheral T- and NK-cell Neoplasias' was
      founded in Frankfurt/M. This group decided on a clinical protocol and a
      scientific program for research on the pathophysiology of these entities.
      Rationales for the therapeutic regimen are the efficacy of cyclophosphamide and
      doxorubicine as shown in protocols for treatment of high grade lymphoma, the
      synergism of cyclophosphamide and fludarabine, and reports demonstrating the
      efficacy of fludarabine in T-cell neoplasias. PATIENTS AND METHODS: Patients will
      be treated with a combination of fludarabine (30 mg/m(2) days 1-3),
      cyclophosphamide (1000 mg/m(2) day 1) doxorubicine (25 mg/m(2) day 2+3) (FCD).
      For patients > or =65 years a dose-reduced FCD regimen will be administered. In
      patients included in the treatment study and additionally in patients with
      indolent disease not requiring therapy, scientific projects on the biology of
      peripheral T- and NK-cell neoplasias will be performed. CONCLUSIONS: Expected
      conclusions of the projected study are the establishment of treatment and
      diagnostic standards, and improvement of classification of these entities by
      clinical, morphologic and biologic parameters.

PMID- 11441298
TI  - Pegylated liposomal doxorubicin in combination with hyperthermia for treatment of
      skin metastases of breast carcinoma: a case report.
AB  - BACKGROUND: Incorporation of doxorubicin hydrochloride into pegylated liposomes
      (PLD) may decrease chemotherapy side effects and increase the activity.
      Hyperthermia could further potentiate its effectiveness. CASE REPORT: A patient
      with skin metastases of breast carcinoma was treated with intravenous infusion of
      PLD (Caelyx) in combination with ultrasound hyperthermia. Each cycle consisted of
      infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41
      43 degrees C for 45 min 1 and 48 h after infusion. A complete remission was
      observed after the combination treatment with no significant toxicity.
      CONCLUSION: Present observations suggest that the combination of PLD with
      hyperthermia of skin metastases of breast carcinoma may be an active and well
      tolerated treatment.

PMID- 11441299
TI  - Porphyrias associated with malignant tumors: results of treatment with ionizing
      irradiation.
AB  - BACKGROUND: Porphyrin metabolism disorders, known as porphyria, represent
      inherited or acquired diseases. The development of porphyria due to light
      sensibility occurs especially with exposure to wavelengths in the range of 300
      700 nm. Skin reactions and neurovisceral dysfunctions are known side effects of
      ionizing irradiation. It can be postulated that during or after ionizing
      irradiation treatment of patients affected with tumor and porphyria, severe side
      effects might appear, in contrast to patients without porphyria. This paper
      describes the treatment of 2 patients affected with tumor and concomitant
      porphyria. PATIENTS: One female patient suffering from intermittent porphyria and
      breast cancer and one male patient suffering from porphyria cutanea tarda and
      bladder cancer were treated with ionizing irradiation (electrons and photons). No
      abnormalities nor any severe general or local side effects could be observed.
      CONCLUSION: Radiation therapy is not a 'stimulating' factor in activating
      porphyria symptoms.

PMID- 11441300
TI  - Treatment of testicular cancer--is quality management possible?
AB  - The incidence of testicular cancer has continuously increased during the last
      decades, especially in the developed countries. The prognosis for a great number
      of young patients with this terminal illness was dramatically improved to a cure
      rate of 95% through the introduction of Cisplatin chemotherapy in the late
      seventies. Einhorn demonstrated the excellent efficacy of Cisplatin in 1977 [see
      1]. At that time, germ cell tumors were the cause of death in 400 males per year
      in Germany. The propagation of chemotherapy could have reduced the number of
      deaths to 100 per year, but in 1996 there were still 200 deaths from this type of
      cancer [2]. This fact demonstrates, firstly, that in general practice, the
      excellent results gained on the efficacy of new agents only asserted themselves
      slowly, and secondly, that even after 20 years, the success rates derived from
      study evaluations on testicular cancer have still not been achieved in practice.
      Although it is accepted that the results of study evaluation are not
      representative for the general population, improved treatment strategies that
      were confirmed as a result of study evaluation have to be implemented more
      rapidly into general therapy. Quality management will ensure the introduction of
      results from study evaluation into general practice. It will also ensure
      continuous progress.

PMID- 11441301
TI  - [Carcinoma of the esophagus--actual epidemiology in Germany].
AB  - Over the last years the incidence of esophageal cancer in Germany has been
      rising. One of the reasons of this rise is the increase of adenocarcinoma (AC) of
      the esophagus, a nearly unknown diagnosis 30 years ago. The incidence of squamous
      cell carcinoma (SCC) is rising, too. The main risk factors for the development of
      SCC as well as for AC are heavy smoking and alcohol. Barrett's esophagus is
      predominantly developing in men after a longer lasting gastroesophageal reflux.
      In consequence, AC of the esophagus will be observed mostly in men. Patients with
      AC differ from patients with SCC by a smaller number of concomitant diseases,
      which are often caused by obesity of patients with AC. The preoperative risk
      factors of patients with SCC are caused by tobacco and alcohol. Only patients
      with early cancer (pT1) of the esophagus have a good prognosis with a 5-year
      survival rate of 83% for AC and 63% for SCC.

PMID- 11441302
TI  - [Magnetic resonance imaging of the breast: costs and efficiency].

PMID- 11441303
TI  - [Report on the NIH Consensus Development Conference on Adjuvant Therapy of Breast
      Carcinoma].

PMID- 11441304
TI  - On the problem of using 'optimal' cutpoints in the assessment of quantitative
      prognostic factors.
AB  - The identification and assessment of prognostic factors is an important task in
      clinical cancer research. Quantitative prognostic factors are often categorized
      by using one or several cutpoints to obtain an easier interpretation with respect
      to prognosis of the resulting patients' subgroups. Considering the selection of a
      data-driven 'optimal' cutpoint as a 'prototype' of statistical model building, we
      demonstrate that prognostic relevance of a single factor with no effect can
      solely be produced by the statistical model building process. Furthermore, we
      show how to overcome these problems by using corrected P-values and shrinkage
      methods. The problem and its solutions are illustrated by using the data of two
      breast cancer studies.

PMID- 11441305
TI  - [Tumor angiogenesis: new approaches to cancer therapy].
AB  - Growth and metastasis of solid tumors depend on the formation of new blood
      vessels which originate from the existing vascular system. These blood vessels
      grow into the tumor and thus provide the necessary nutrients and growth factors
      for tumor progression. At the same time, the newly formed blood vessels allow
      tumor cells to disseminate and form metastases in distant organs. Normally,
      vascular homeostasis is regulated by a balance of angiogenic and antiangiogenic
      mechanisms. Tumor-induced angiogenesis is mainly sustained by the production and
      secretion of angiogenic factors originating from tumor and stroma cells. The most
      prominent angiogenic factor is the vascular endothelial growth factor (VEGF).
      Recently, additional angiogenic factors and their respective receptors have been
      identified and related to tumor angiogenesis. Among these, the angiopoietins and
      their receptor TIE-2 have been investigated to some detail. Angiopoietin-1 which
      binds to and activates TIE-2 is obviously responsible for the stabilization of
      vessels under homeostatic conditions. Angiopoietin-2 binds to the same receptor
      as angiopoietin-1 but is antagonistic with respect to angiopoietin-1. It
      destabilizes blood vessels and, under appropriate conditions, induces complete
      regression. In the similar situation angiopoietin-2 induces the destabilization
      of blood vessels, and the angiogenic factor VEGF produced by the tumor induces
      the massive formation of new vessels. When human melanoma cells A375 are stably
      transfected to produce the soluble variant of the angiopoietin receptor TIE-2
      (sTIE-2), they show a substantial inhibition of tumor growth on nude mice.
      Similar effects have been seen with the soluble variant of the VEGF receptor FLT
      1 (sFLT-1). In both cases, the vessel density of the tumors is significantly
      reduced. These experiments show that the inhibition of the angiopoietin/TIE-2
      system, similar to the inhibition of the VEGF/VEGF receptor system, has an
      antitumoral effect, most probably due to the inhibition of tumor angiogenesis.
      Thus, inhibition of both signalling systems seem to be a valid strategy for the
      development of novel antiangiogenic therapies. Recently, the inhibition of the
      VEGF receptor tyrosine kinase by the compound PTK787/ZK222584 has been shown to
      substantially inhibit tumor growth and metastases formation. This compound has
      now entered clinical trials at the Tumor Biology Center in Freiburg i.Br. A
      preliminary evaluation of phase I study shows a very promising clinical outcome.

PMID- 11441306
TI  - [From tumor necrosis factor to TRAIL-AMAIZe: second generation antitumorally
      effective cytokines].

PMID- 11441307
TI  - [Possible value of positive PSA levels in malignant and nonmalignant breast
      diseases].
AB  - Measurement of serum levels of PSA is widely used as a screening tool for
      prostate cancer. PSA has been shown to be associated with malignancies of many
      other organs than prostate, including the female breast. Therefore, PSA is not
      prostate-specific. PSA serum levels in females increase with excess of androgens.
      Variable PSA expression was observed in membranes of adipocytes of fat tissue and
      in the endothelium of small vessels in female and male breast. There is
      increasing evidence that androgens play a significant role in the development and
      progression of breast cancer. 5alpha-reductase is an enzyme that is expressed in
      androgen-dependent tissues, including the female breast, catalyzing the reduction
      of testosterone to its more bioactive form, dihydrotestosterone, which then
      transactivates a number of genes. One of these genes encodes for PSA, a favorable
      prognostic factor in breast cancer. Interactions of PSA and sex hormones in
      physiological processes and in prostatic and mammary cancer have been reported.
      The possible influence of PSA on breast cancer growth and progression and even
      its physiological functions are still under controversial debate. There are some
      findings which might indicate similarities in the influence of steroid hormones
      on the development of prostate and breast malignancies, perhaps a unique hormone
      dependent molecular pathway for both types of cancer.

PMID- 11441308
TI  - [Drug development from phospholipids].

PMID- 11441309
TI  - [Clinical trials: prerequisite of evidence-based oncology: reality, perspectives
      and a new tool recruited--the Internet].
AB  - Scientifically sound clinical research is an undispensable prerequisite to
      establish innovative therapeutic principles, to support applications for
      marketing authorization of proprietary new drugs, to advance therapeutic results
      in cancer therapy, and the only route towards an evidence-based clinical oncology
      at the advent of the 21st century. Treatment of cancer patients based on
      scientific evidence derived from clinical studies outperforms compassionate
      individual therapeutic decisions with a lack of evidence, whenever such evidence
      is available or whenever a clinical trial is addressing the clinical situation
      that must be addressed for an individual patient. A stable trend towards improved
      survival of cancer patients was first observed in 1999. The advent of new
      technologies of drug design, the integration of pharmacology, genomics and DNA
      microarray chip technologies will produce a myriad of new anticancer drugs with
      promising potential for cancer therapy that need to be tested in the clinical
      setting without delay. To match that challenge, clinical oncology must streamline
      the laborious process of conducting clinical trials. The process of planning,
      multicenter coordinating, recruiting, treatment, analyzing, and reporting of
      clinical trial results must be further optimized. The best possible quality
      control of all steps of that process is a prerequisite to motivate patients to
      participate in clinical trials of cancer therapy - always one of the most
      promising treatment options for patients seeking the best possible cancer care.
      At the same time as the internet goes mainstream and cancer care information is
      ubiquitously laymanized and dispersed via cancer cybermedicine, clinical
      researchers may employ the internet to exchange information, facilitate
      conduction of clinical trials, and facilitate recruitment to clinical studies via
      web-based trial registries. This will be more than an incremental step forward to
      deliver the best possible clinical care towards the ultimate goal: to deliver
      evidence-based medicine en route to a cure for more cancer patients than ever.

PMID- 11441310
TI  - [German Hodgkin's Lymphoma Study Group].

PMID- 11441311
TI  - [Long-term results with MACOP-B and radiation therapy for aggressive lymphomas].
AB  - BACKGROUND: Long-term results are needed to evaluate chemotherapy regimens and
      prognostic factors in non-Hodgkin's lymphomas (NHL). We report the 10-year follow
      up data of aggressive NHL classified according to the Kiel classification and
      treated with MACOP-B. PATIENTS AND METHODS: Between 1985 and 1991, 71 patients
      with aggressive NHL were treated in a single institution with MACOP-B and
      adjuvant radiotherapy as first-line therapy. NHL subtypes were classified
      according to the updated Kiel classification. Follow-up data were available until
      1998. RESULTS: The overall survival (OS) at 10 years is 45% (confidence interval
      33-57%), the progression-free survival 42% (30-54%), and the relapse-free
      survival of the 59 patients (82%) in complete remission is 52% (39-65%). The Kiel
      classification combined with the International Prognostic Index (IPI) identified
      diffuse large B-cell and anaplastic large T-cell lymphomas with IPI 0-2 as
      subgroups with very favorable prognosis after MACOP-B (OS 84% and 80% at 10
      years). Late relapses (>2 years after therapy) did occur in these patients but
      had a good prognosis after second remission. Only 3 of 24 relapses were in the
      radiation field. Three patients died of toxicity, 1 during MACOP-B (1.3%). Risk
      factors for therapy-related death were age and pulmonary toxicity. Most patients
      suffered from chemotherapy-associated mucositis. Osteoporosis was a common late
      toxicity (39%). Three second cancers but no leukemias or myelodysplastic
      syndromes were observed during follow-up. CONCLUSIONS: MACOP-B in combination
      with adjuvant radiotherapy is highly effective in diffuse large B-cell or
      anaplastic large T-cell-lymphomas with IPI 0-2. Patients with IPI >2 or with
      centrocytic or secondary centroblastic B-cell or non-anaplastic T-cell lymphomas
      need more intensive therapy or novel approaches. Regarding the toxicity profile,
      MACOP-B should be replaced by VACOP-B.

PMID- 11441312
TI  - [Minimally invasive percutaneous ablation of malignant hepatic tumors].
AB  - Three minimally invasive techniques for the treatment of primary and secondary
      malignant hepatic tumors - percutaneous ethanol injection, laser-induced
      thermotherapy and percutaneous radiofrequency thermotherapy--are reviewed and
      discussed. The initial clinical results suggest that these technics are safe and
      potentially effective in selected patients with inoperable liver tumors.

PMID- 11441313
TI  - [Adjuvant chemotherapy in breast cancer--is omission an error?].
AB  - Adjuvant chemotherapy in women with breast cancer is currently regarded as
      standard procedure. An efficacy of 10-20% can only be viewed as modest, even if a
      statistically significant prolonging of disease-free interval and overall
      survival has been established. The value of this mode of therapy is questionable
      because 80-90% of patients are subjected to chemotherapy with no effect, i.e.
      they would either have remained well regardless, or they are primarily resistant.
      In both cases, they are prone to suffering significant side effects. The cost
      benefit ratio also needs to be taken into consideration. It is therefore
      recommended that the therapeutic effect is depicted in absolute percentages and
      not in relative percentages and absolute numbers. Only rendering the results as
      absolute percentages allows a true comparison between the small number of
      patients who benefit and the vast majority who do not. Even if this mode of
      therapy is regularly implemented worldwide by doctors, requested by patients and
      understandably backed by industry, the central question remains: 'How great do
      the benefits of a particular therapy have to be, in order to justify its use? Who
      should set the limits?' For the time being it therefore does not appear to be a
      mistake not to subject the patients in question to chemotherapy, unless they are
      part of a study.

PMID- 11441314
TI  - [Status and perspectives of rehabilitation of oncological patients in Germany].

PMID- 11441315
TI  - [Psychooncology and its importance in oncology: actual trends and future tasks of
      research].

PMID- 11441316
TI  - [Care at the Tumor Biology Center Freiburg--on the way].
AB  - The concepts of salutogenesis on the one hand and of a management which aims at
      getting the employees involved into decision-making processes on the other are
      two core concepts of the Tumor Biology Center, opened in 1993 in Freiburg i.Br.,
      Germany. In this framework nursing--like other health professions--has its own
      specific task. Nurses with their holistic approach are especially concerned with
      health promotion. They are involved in various interprofessional teams like the
      so-called pain conference, the ethics committee, quality circles, and
      psychological supervision. The Department of Nursing is committed to the
      scientific orientation of the Tumor Biology Center. Nursing research started
      right at the opening of the hospital. Today, the most important project is the
      implementation of nursing diagnosis. National and international conferences are
      organized to foster the development of nursing science in Germany.

PMID- 11441317
TI  - [Gerd A. Nagel and the Journal ONKOLOGIE].

PMID- 11441318
TI  - Class effects of pharmaceuticals and therapeutic interchangeability.

PMID- 11441319
TI  - Do we need to accredit clinical research?

PMID- 11441320
TI  - Age-related differences in the use of cardiac medications in patients with
      coronary artery disease.
AB  - BACKGROUND: Benefits of aspirin and beta-blocker use in patients with coronary
      artery disease and angiotensin-converting enzyme (ACE) inhibitors in those with
      left ventricular systolic dysfunction are well documented in all age groups.
      OBJECTIVE: To investigate whether aspirin, beta-blockers, and ACE inhibitors are
      equally used in geriatric (> or =65 years) versus younger (<65 years) patients
      with coronary artery disease. SETTING: University-affiliated major academic
      hospital. METHODS: Records of 402 patients with coronary artery disease were
      analyzed for use of aspirin, beta-blockers, and ACE inhibitors. One hundred
      thirty patients with contraindications to use of these agents were excluded.
      RESULTS: Of 272 study patients, 85% were using aspirin and 71% beta-blockers.
      Among the patients with left ventricular systolic dysfunction, 79% were using ACE
      inhibitors. One hundred forty-seven patients were of geriatric age, whereas 125
      were of younger age. No significant difference in the use of aspirin (82% versus
      89%, P = 0.10), beta-blockers (71% versus 70%, P = 0.85), or ACE inhibitors (86%
      versus 69%, P = 0.13) was found between geriatric and younger patients. This lack
      of difference in use of cardiac medications between geriatric and younger
      patients persisted on gender-based subgroup analysis. On decade-of-age-based
      analysis, aspirin use was not equally distributed among all the decades of age (P
      < 0.005), but beta-blocker use was. CONCLUSION: Results of this study demonstrate
      equal use of aspirin, beta-blockers, and ACE inhibitors in geriatric versus
      younger patients with coronary artery disease. Aspirin use was not equally
      distributed among all the decades of age.

PMID- 11441321
TI  - Relative variability in bioavailability of oral controlled-release formulations
      of oxycodone and morphine.
AB  - A retrospective analysis compared the coefficients of variation associated with
      the maximum plasma concentration (Cmax) and the extent of absorption (area under
      the curve [AUC] from 0 hour to the last observation) for oral, controlled-release
      tablet formulations of oxycodone (OxyContin) and morphine (MS Contin). Data from
      fasting, male subjects aged 18 to 45 years were taken from five controlled
      release oxycodone (N = 82) and seven controlled-release morphine (N = 101) single
      dose, bioequivalence studies. The coefficients of variation of Cmax and AUC were
      approximately 33% less for controlled-release oxycodone than for controlled
      release morphine (P =.005). The variation from the minimum to maximum value was
      two to three times less for controlled-release oxycodone than for controlled
      release morphine. Among healthy male subjects, the absorption of oxycodone from
      oral controlled-release oxycodone was significantly more consistent than the
      absorption of morphine from oral controlled-release morphine in terms of both
      maximum absorption and extent of absorption.

PMID- 11441322
TI  - Interspecies scaling of inhalational anesthetic potency minimum alveolar
      concentration (MAC): application of a correction factor for the prediction of MAC
      in humans.
AB  - The objective of this study was to predict minimum alveolar concentration (MAC)
      of inhalational anesthetics in humans from animal data. The MAC of 10 anesthetics
      was obtained from the literature. At least three animal species (excluding
      humans) were used in the scaling. Interspecies scaling of MAC was performed in
      two ways: (1) using the traditional allometric approach, the MAC of each drug was
      plotted against the body weight of the species on a log-log scale, and MAC in
      humans was predicted from the resultant equation; and (2) MAC in each species was
      multiplied by a correction factor obtained by adjusting the lung weight of the
      species based on per kg body weight. The product of the correction factor and the
      MAC was then plotted against body weight as described in the traditional
      approach. Predicted MAC values in humans from animal data using simple allometry
      produced comparatively more error than the prediction made by incorporating the
      correction factor into the scaling. The results of this study indicate that MAC
      may not be predicted in humans from animal data using simple allometry; however,
      applying a correction factor may significantly improve the prediction of MAC in
      humans from animal data.

PMID- 11441323
TI  - Some plasma pharmacokinetic parameters of isoniazid in the presence of a
      fluoroquinolone antibacterial agent.
AB  - The effects of ciprofloxacin (CP), a fluoroquinolone antibacterial agent, on the
      extent of absorption of isoniazid (INH) and on some of its pharmacokinetic
      parameters were investigated in six healthy female volunteers between the ages of
      23 and 32 years. The presence of CP led to increase in the amount of INH and to a
      slight reduction in its peak plasma concentration (Cmax). There was a 1-hour
      increase in the time to attain Cmax (tmax) of INH, indicating absorption
      interaction between the two drugs. This absorption interaction was related to
      inhibition of cholinergic neurotransmission caused by CP, which is capable of
      inhibiting gastric motility, leading to a delay in gastric emptying. The rate of
      elimination (K) and plasma half-life (t1/2) of INH were not significantly
      affected (P = 0.05). The extent of absorption interaction that may have occurred
      (based on values of 24-hour values for area under the concentration curve, Cmax,
      Tmax, K, and t1/2) was considered to be of no therapeutic consequence, and the
      coadministration of the two drugs may be recommended in clinical practice.

PMID- 11441324
TI  - Sugar-free zinc gluconate glycine lozenges (Cold-Eeze) do not adversely affect
      glucose control in patients with type 1 or type 2 diabetes mellitus.
AB  - Several controlled clinical trials have shown that zinc gluconate glycine
      lozenges can reduce symptom severity and duration of symptoms in patients with
      the common cold. Over-the-counter zinc lozenges are used commonly by the general
      population, including people with diabetes. The purpose of this study was to
      assess the effects of sugar-free Cold-Eeze (The Quigley Corp., Doylestown, PA), a
      commonly used zinc preparation, on glucose control in patients maintained on
      stable antidiabetic therapy. Forty-eight patients with either type 1 (n = 3) or
      type 2 (n = 45) diabetes were randomized in a 3:1 ratio to receive either zinc
      lozenges (four to six lozenges/day for 10 days) or matching placebo. The primary
      endpoint was change in serum fructosamine concentration. Secondary endpoints
      included daily home glucose and fasting blood glucose monitoring (baseline, days
      10 and 21). The mean age for all patients was 54 years (range, 25 to 76), with
      slightly more women (60%). The treatment groups did not differ with respect to
      age, sex, body mass index, duration of diabetes, baseline hemoglobin A1C level,
      or fasting plasma glucose level. The patients treated with placebo (n = 13) and
      zinc (n = 34) had similar fructosamine levels (mean +/- SD) at baseline (318 +/-
      90 versus 297 +/- 86 micromol/l, respectively). After 10 days of dosing, both
      groups showed modest reductions in serum fructosamine (-7 +/- 42 and -9 +/- 90
      micromol/l). These changes were not statistically significant. In conclusion,
      these findings suggest that sugar-free zinc lozenges can be administered safely
      to patients with diabetes without deleterious effects on glycemic control.

PMID- 11441325
TI  - Beneficial effect of human albumin on neonatal cerebral edema.

PMID- 11441326
TI  - Oral nutritional supplements and heart disease: a review.
AB  - The use of nutritional supplements in the treatment of cardiovascular disease is
      rapidly growing in the United States. Many substances are marketed with anecdotal
      claims of efficacy. Most have not been scientifically studied. Excitement exists
      in the lay press about the homocysteine hypothesis of coronary artery disease and
      vitamin cures. A MEDLINE search and review of papers covering the study of
      popular nutritional supplements were undertaken. The papers were limited to peer
      review journals using patient series reports, double-blinded prospective studies,
      and population studies. A compendium of the available data was obtained and an
      analysis of each paper's methodology was done. A review of the most popular and
      most studied oral nutritional supplements for the treatment of heart disease
      demonstrated relatively few well-founded indications for the widespread
      application of substances with the exception of the bioflavonoids. Some modest
      effects for endothelial dysfunction were noted for vitamins C and E. Red wines
      and beers were also noted to be beneficial. The majority of substances either had
      no effect or were deleterious.

PMID- 11441327
TI  - Clinical pharmacology of furosemide in children: a supplement.
AB  - Furosemide is one of the most effective and least toxic diuretics used in
      pediatric practice. Experimental and clinical data suggest that
      adrenocorticosteroids and/or endogenous ouabain-like substances may play an
      important role in its diuretic effect. Also, the drug appears to have anti
      inflammatory properties. In children with different diseases who received orally
      or intravenously 1 to 2 mg/kg doses of furosemide, a statistically significant
      positive linear relationship was found between the drug urinary excretion rate
      and the urine flow rate, but log dose-response curves to the drug were found to
      vary depending on the disease and the route of the drug administration. No
      sigmoid-shaped log dose-response curve (ie, one approaching a zero response at
      very low furosemide urinary excretion rates and a maximum response at very high
      excretion rates) was attained, which may suggest that the capacity of the kidney
      tubules to respond diuretically to the aforementioned doses of furosemide was not
      exceeded in these patients. However, in infants with different diseases and
      reasonably normal renal function who required administration of this diuretic, a
      very steep log dose-response curve to a 1 mg/kg intravenous dose of furosemide
      was found, which may suggest that higher doses may not result in a significant
      increase in diuretic response. The lowest mean furosemide urinary excretion rate
      and its concentration in urine associated with a significant diuresis were found
      to be 0.58 +/- 0.33 microg/kg/min and 24.2 +/- 10.5 microg/ml, respectively.
      Also, a significant correlation was found between the amount (in milligrams) of
      furosemide excreted in the urine during the first 6 hours after administration
      and the urine volume collected during that time. Patients with cystic fibrosis
      appeared to have a markedly more pronounced diuretic response to the average oral
      dose of 0.835 +/- 0.18 mg/kg than that reported in control children given 2
      mg/kg. In children with acute renal failure caused by acute gastroenterocolitis
      or glomerulonephritis, a broad relationship was observed between a single
      intravenous dose and diuretic response after administration of furosemide (1.2 to
      30.8 mg/kg). It was suggested that the total daily dose of the drug should not
      exceed 100 mg in these patients. Furosemide was found to be effective in
      management of bronchoconstriction accompanying chronic lung disease and narrowing
      of the upper respiratory airways; in hydrocephalus in infancy to avoid
      cerebrospinal fluid shunts; in some diagnostic procedures, such as an assessment
      of fetal and neonatal hydronephrosis; and in evaluation of different types of
      renal tubular acidosis. Among side effects accompanying clinical use of this drug
      were cholelithiasis in premature infants receiving total parenteral nutrition
      concomitantly with the diuretic; secondary hyperparathyroidism and bone disease
      in infants obtaining long-term furosemide treatment; and drug-induced fever.

PMID- 11441328
TI  - Allergen-induced inflammation and the role of immunoglobulin E (IgE).
AB  - The prevalence of common allergic disorders such as asthma, allergic rhinitis,
      and atopic dermatitis has increased significantly in the past 30 years. The
      impact of these atopic diseases on the patient and the health care system is
      considerable: Allergic disorders are associated with a high degree of morbidity,
      which can profoundly impact patient quality of life and health care resource use.
      Existing strategies to treat allergic disorders beyond simple allergen avoidance
      focus on diminishing or eliminating the recurrent and/or persistent signs and
      symptoms that characterize the allergic response. A new strategy has been
      developed that uses antibodies directed against immunoglobulin E (IgE) to prevent
      it from binding to cells bearing its receptors and thus neutralizing the allergic
      response before it begins. These new agents reduce allergic responses in atopic
      individuals and improve their symptoms while reducing rescue medication and
      corticosteroid use in patients with allergic asthma or seasonal allergic
      rhinitis. Thus, anti-IgE antibodies represent proof that IgE plays a central role
      in allergic reactions and that anti-IgE therapy is a potentially effective
      treatment for allergic disease.

PMID- 11441329
TI  - Cocaine-induced torsades de pointes in idiopathic long Q-T syndrome.
AB  - Torsades de pointes is a ventricular tachycardia characterized by the QRS
      complexes of changing amplitude that appear to twist around an isoelectric line.
      It usually precipitates in the setting of underlying Q-T interval prolongation,
      which has both congenital and acquired causes. The common acquired causes of
      torsades precipitation are medications, electrolyte imbalance, and severe
      bradycardia. This report presents a case of torsades de pointes that was
      precipitated by substance abuse in a patient with idiopathic long Q-T syndrome
      and required several treatment modalities.

PMID- 11441330
TI  - Atrial fibrillation associated with systemic lupus erythematosus and use of
      methylprednisolone.
AB  - Systemic lupus erythematosus is known to have cardiac manifestations consisting
      of pericarditis, myocarditis, endocarditis, and coronary vasculitis. Pericarditis
      is the most common cardiac manifestation of systemic lupus erythematosus.
      Myocarditis may be suspected in patients presenting with unexplained tachycardia,
      conduction disturbances, unexplained systolic dysfunction with or without heart
      failure, or arrhythmias. The development of arrhythmias in systemic lupus
      erythematosus could be secondary to pericarditis, myocarditis, or ischemia caused
      by coronary vasculitis. The development of atrial fibrillation in systemic lupus
      erythematosus is not commonly reported. There have been few reports on the
      patients developing atrial fibrillation after being started on methylprednisolone
      therapy. Described here is a case of the development of atrial fibrillation in a
      newly diagnosed 37-year-old patient with systemic lupus erythematosus who was
      started on intravenous methylprednisolone therapy.

PMID- 11441334
TI  - Human molecular embryogenesis: an overview.
AB  - Molecular embryology is a rapidly evolving field of great complexity. This
      overview is primarily for the newcomer to this field, in an attempt to demystify
      the processes by which a human single-celled zygote eventually forms an embryo.
      Although all embryonic cells share the same genetic information, they
      differentiate according to the basic plan dictated not only by multiple families
      of transcription factors to silence some genes and activate others but also
      through DNA methylation, histone acetylation, and heterochromatinization.
      Regional expression of various transcription factors causes embryos to establish
      primary embryonic axes. Once the basic body plan is established, the region
      specific diversity becomes progressively finer, and each cell eventually develops
      a "molecular address" characterized by the expression of specific genes. The
      overview is divided into two main parts: embryonic cell growth and morphogenesis.
      At the present time, more is known about the details of molecular regulation of
      the embryonic growth than about morphogenesis.

PMID- 11441335
TI  - Hepatocellular ubiquitin expression in alpha1-antitrypsin deficiency.
AB  - Studies of the ubiquitin-proteasome system in alpha1-antitrypsin (AAT) deficiency
      have been performed using only biochemical and molecular biology techniques on
      human cells as well as on AAT-deficient transduced cell lines. The objective of
      our study was to assess the immunohistochemical and topographic features of
      ubiquitin in the livers of AAT-deficient children with and without active liver
      disease. Fourteen cases of AAT deficiency were retrieved from our archives, along
      with 10 control liver specimens obtained from autopsies of age-matched children
      with no clinical, gross anatomic, or histologic evidence of liver disease. Twelve
      of 14 cases of AAT deficiency were cirrhotic explanted livers from
      transplantations procedures. Two cases were noncirrhotic liver biopsies from
      asymptomatic patients. Periodic acid-Schiff (PAS) histochemistry and AAT
      immunostains were performed on all AAT-deficient liver specimens to verify the
      diagnosis. Immunohistochemistry with polyclonal ubiquitin antibodies was
      performed on all specimens. Ubiquitin immunoreactivity was present in all AAT
      livers while control livers were consistently negative or weakly reactive. In
      cirrhotic livers, ubiquitin immunoreactivity was strongest in the cytoplasm
      whereas the characteristic PAS-positive, diastase-resistant cytoplasmic granules
      appeared nonreactive. However, not all cirrhotic livers showed this pattern. Some
      were only focally positive (<5% of hepatocytes). In asymptomatic patients,
      ubiquitin staining was diffuse and moderate to prominent, and evenly distributed
      within individual hepatocytes and lobules. We therefore conclude that the
      ubiquitin-proteasome pathway is operative in the hepatocytes of AAT-deficient
      livers, as illustrated by the study of ubiquitin immunoreactivity. However, some
      AAT-deficient livers are only focally immunoreactive for ubiquitin. This may
      indicate an intrinsic defect of the ubiquitin-proteasome system in some patients.

PMID- 11441336
TI  - Wnt signaling in human development: beta-catenin nuclear translocation in fetal
      lung, kidney, placenta, capillaries, adrenal, and cartilage.
AB  - The Wnt signaling pathway is involved in both normal development and
      tumorigenesis. Activation of the pathway results in stabilization and nuclear
      translocation of beta-catenin protein. Nuclear localization of beta-catenin has
      been used to identify tumors in which mutations in APC or beta-catenin activate
      Wnt signaling. We analyzed the subcellular localization of beta-catenin
      immunohistochemically in human fetal and postnatal tissues to identify activation
      of Wnt signaling during development. Nuclear beta-catenin is present in capillary
      endothelium, mesenchyme surrounding renal tubules, adrenal cortex, cartilage
      anlage, placental cytotrophoblast, and pulmonary acinar buds. These
      investigations suggest a defined role for Wnt signaling in human fetal
      development and provide a catalogue of non-neoplastic tissues with nuclear beta
      catenin staining.

PMID- 11441337
TI  - Origin of cardiac mucosa: ontogenic consideration.
AB  - The origin and histology of the cardiac mucosa remains controversial. The
      classical concept that the cardiac mucosa is of gastric origin has been
      challenged by those who advocate that the cardiac mucosa results from a
      metaplastic esophageal process. Some regard cardiac mucosa as consisting solely
      of pure mucous glands, whereas others accept the presence of isolated parietal
      cells within the mucous gland (mixed glands). In this study, we have clarified
      the presence and site of origin of the cardiac mucosa and its histological
      composition. To do so we studied the microscopic characteristics of the gastric
      side of the squamous-columnar junction (SCJ) of 77 autopsied fetuses of different
      gestational ages (prenatal group) and of infants, young children, and adolescents
      (postnatal group). We evaluated the presence or absence of a transitional zone,
      defined as the area between the squamous esophageal and oxyntic mucosa, the
      glandular composition of the transitional zone (i.e., pure mucous and mixed
      glands), and the presence or absence of inflammation. Our study revealed that a
      transitional zone with the microscopic characteristics of cardiac mucosa was
      universally present at the SCJ. The microscopic characteristics of this zone
      varied with age. Both pure mucous and mixed glands were observed. We conclude
      that the cardiac mucosa is partially if not entirely the result of normal
      embryonic gastric development. Both mucous and mixed glands constitute normal
      components of the cardiac mucosa.

PMID- 11441338
TI  - Expression of thyroid transcription factor-1, surfactant proteins, type I cell
      associated antigen, and Clara cell secretory protein in pulmonary hypoplasia.
AB  - Pulmonary hypoplasia (PH) is a developmental abnormality characterized by
      diminished distal lung parenchyma. Recent studies have demonstrated that thyroid
      transcription factor 1 (TTF-1), a member of NKx2 family of homeodomain
      transcription factors, plays an important role in lung organogenesis and lung
      epithelial gene expression. In order to evaluate whether abnormal expression of
      TTF-1 contributes to the pathophysiology of PH, we studied the expression of TTF
      1, as well as that of the surfactant proteins (SPs), Clara cell secretory protein
      (CCSP), and type I cell-associated antigen (T1 cell-Ag), in PH.
      Immunolocalization patterns of these proteins were evaluated in 15 cases of PH
      with different associated diseases and compared with those of 14 matched
      controls. Our study demonstrated that the concentration gradient of TTF-1 along
      the proximal-distal axis in normal fetal lung is disrupted in PH after 24 weeks
      gestational age, while the expression of the SPs, CCSP, and T1 cell-Ag seemed to
      be preserved. We conclude that a normal TTF-1 expression pattern might be crucial
      in the control of distal lung development. Failure to switch off expression of
      TTF-1 in PH of more than 24 weeks gestational age may be a final common pathway
      leading to PH associated with the disease processes investigated in this study.

PMID- 11441339
TI  - Grade and stage in chronic hepatitis.
AB  - The liver biopsy is essential to the investigation and management of chronic
      liver disease. The pathologist provides an etiologic diagnosis, reports the grade
      of disease activity and stage of fibrosis, and comments on any response to
      therapy. Recent progress in our understanding of chronic hepatitis, its causes,
      prognosis, and therapy, has influenced the revision of its nomenclature and
      classification. The use of a descriptive or numerical scoring system allows the
      pathologist to provide reproducible, clinically relevant information in the
      surgical pathology report.

PMID- 11441340
TI  - Nesidioblastosis and mixed hamartoma of the liver in Beckwith-Wiedemann syndrome:
      case study including analysis of H19 methylation and insulin-like growth factor 2
      genotyping and imprinting.
AB  - An infant with persistent hyperinsulinemic hypoglycemia, diffuse
      nesidioblastosis, and mixed hamartoma of the liver (MHL), in addition to
      demonstrating clinical, pathologic, and molecular manifestations of Beckwith
      Wiedemann syndrome (BWS), is the subject of this report. H19 methylation assay
      and allelic expression analysis for insulin-like growth factor 2 (IGF2) indicated
      that the patient was mosaic for paternal isodisomic cells and normal cells in
      lung tissue, nontumoral liver tissue, tissue from the MHL, and pancreatic tissue.
      We propose that abundant IGF2 expression during development due to paternal
      isodisomy resulted in hepatomegaly and islet cell hyperplasia, which led to
      nesidioblastosis. MHL, by contrast, may have resulted from a decrease in disomic
      cells, compared with nontumoral liver tissue, which showed an increase in disomic
      cells. Thus, somatic mosaicism may result in unbalanced tissue growth, which may
      contribute to the formation of MHL in BWS.

PMID- 11441341
TI  - Small round cell tumor with biphenotypic differentiation and variant of
      t(21;22)(q22;q12).
AB  - A 14-year-old boy presented with a soft tissue swelling on the outer aspect of
      his left upper arm. Examination of the tumor by light microscopy showed a small
      round cell tumor with a rare focus of myogenic differentiation. Myogenic
      differentiation was confirmed on ultrastructural examination by
      immunohistochemistry and reverse transcriptase polymerase chain reaction (RT
      PCR). Conventional G-banding and fluorescent in situ hybridization (FISH)
      demonstrated a complex variant of t(21;22)(q22;q12). By RT-PCR, the EWS-ERG
      fusion transcript was defined as type 9e. This tumor was unusual in that it
      showed characteristics of myogenic and neural differentiation, and contained a
      rearrangement of the EWS gene consistent with a diagnosis of Ewing's sarcoma.
      This supports the hypothesis that a class of biphenotypic childhood sarcomas,
      with features of myogenic and neural differentiation, exists that may be related
      to the Ewing's sarcoma family of tumors.

PMID- 11441342
TI  - Neutrophil-rich anaplastic large cell lymphoma of the skull presenting after head
      trauma.
AB  - The presentation of anaplastic large cell lymphoma in bone is uncommon. We report
      a case of anaplastic large cell lymphoma of the skull that was diagnosed after
      head trauma. Biopsy revealed significant destruction of the outer table of the
      frontal bone. Histopathologically, the initial evaluation suggested osteomyelitis
      because of a mixed inflammatory infiltrate with large numbers of neutrophils.
      However, several clusters and individual mononuclear cells were atypical. The
      tumor cells had large, pleomorphic nuclei; these cells stained positively with
      antibodies to Ki-1 (CD 30), ALK-1, and EMA. Fluorescence in situ hybridization
      (FISH) showed rearrangement of the ALK gene, which usually results from the
      t(2;5) translocation, present in most anaplastic large cell lymphomas. There was
      no evidence of systemic disease. The patient has tolerated chemotherapy and is
      free of disease 12 months later.

PMID- 11441343
TI  - Cytogenetic and molecular characterization of a congenital mesoblastic nephroma.
AB  - A newborn baby boy was diagnosed with the mixed form of congenital mesoblastic
      nephroma (CMN) representing both classic and cellular histology features in the
      renal tumor. Additionally, the patient had skin and bone lesions consistent with
      multifocal involvement of a generalized infantile fibromatosis (IFS). Both skin
      and bone lesions were distinctly different from CMN and did not represent
      metastasis. The primary tumor cell line (MCH-MN-1), established from the resected
      right kidney tumor, had a diploid DNA content. Cytogenetic studies revealed
      deletion on the long arm of chromosome 3 (q21q24) and duplication on the short
      arm of chromosome 11 (p15). MCH-MN-1 cells expressed ETV6-NTRK3 gene fusion
      transcripts, characteristic of cellular and mixed forms of CMNs. The cells had
      high p21 and low Bax mRNA expression in the reverse transcriptase-polymerase
      chain reaction (RT-PCR) assay. The high level of proliferative marker (Ki67) mRNA
      expression correlated well with the pluripotent nature of MCH-MN-1 in tissue
      culture (cell doubling time = 12.4 h). Our results showed that MCH-MN-1 might be
      a good model cell line for investigations on mesoblastic nephroma.

PMID- 11441369
TI  - Primary aneurysmal bone cysts: 16q22 and/or 17p13 chromosome abnormalities.

PMID- 11441370
TI  - Selective serotonin reuptake inhibitors: Their effect on high-intensity exercise
      performance.
AB  - OBJECTIVE: To determine the neuromuscular and performance effects of acute and
      long-term exposure to selective serotonin reuptake inhibitors (SSRIs). DESIGN:
      Two randomized, double-blind, crossover studies. SETTING: Departments of
      Kinesiology and Medicine, McMaster University, Hamilton, Ont, Canada.
      PARTICIPANTS: Eleven healthy, college-aged men in the acute study; 12 healthy,
      college-aged men in the chronic study. INTERVENTIONS: In the acute study,
      subjects were given a placebo and fluoxetine (40 mg) 6 hours before testing, in
      the chronic study, they were given fluoxetine (40mg/d) and an identical placebo
      for 2 weeks before testing. MAIN OUTCOME MEASURES: Target measures were maximum
      voluntary contractions (MVCs), evoked peak torque, and percentage of motor unit
      activation for muscle strength and central drive. Repeated Wingate cycle
      ergometer tests were used to measure anaerobic power, capacity, and fatigue
      index. VO2max tests (80%, 90%) were used to measure time to exhaustion and
      cardiorespiratory responses. RESULTS: In the acute study phase, MVC was lower for
      fluoxetine versus placebo (p =.05) and a slight fatigue resistance was measured
      in the repeated Wingate tests for the fluoxetine group; however, there were no
      affects on any other measured variable. In the chronic study phase, minute
      ventilation was lower for the fluoxetine trial (p <.05); however, there were no
      treatment affects on any of the other measurements. CONCLUSION: Acute and chronic
      SSRI intake does not effect strength or high-intensity exercise performance in
      young adult men.

PMID- 11441371
TI  - Velocity training induces power-specific adaptations in highly functioning older
      adults.
AB  - OBJECTIVE: To test the efficacy of high-velocity training in healthy older
      persons. DESIGN: A 12-week randomized trial, with subjects blocked for gender and
      residence, comparing high-velocity resistance training with a self-paced walking
      program. SETTING: Retirement community. PARTICIPANTS: Forty-three volunteers over
      the age of 70 years. INTERVENTION: Power group: high-velocity leg exercises 3
      times weekly with weekly increases in resistance combined with 45 minutes of
      moderate, nonresistance exercise weekly. Walking group: moderate intensity
      exercise 30 minutes daily, 6 days weekly. MAIN OUTCOME MEASURES: Variables
      measured included leg press peak power and leg extensor strength. Functional
      performance outcomes included: 6-minute walk distance, Short Physical Performance
      Battery, Physical Performance Test, and Medical Outcomes Study Short-Form Health
      Survey. RESULTS: Peak power improved 22% (p =.004) in the power group (3.7 +/-
      1.0 W/kg to 4.5 +/- 1.4 W/kg) but did not change in the walking group (3.99 +/
      .76 W/kg to 3.65 +/-.94 W/kg). Leg extensor power at resistance of 50%, 60%, and
      70% of body weight increased 50%, 77%, and 141%, respectively, in the power group
      (p <.0001, repeated-measures analysis of variance). Strength improved 22% in the
      power-trained individuals and 12% in the walkers (p <.0001). Training did not
      improve functional task performance in either group. One subject developed a
      radiculopathy during training. CONCLUSIONS: Resistance training focusing on speed
      of movement improved leg power and maximal strength substantially, but did not
      improve functional performance in healthy high-functioning older volunteers.

PMID- 11441372
TI  - Treadmill training improves fitness reserve in chronic stroke patients.
AB  - OBJECTIVE: To investigate the hypothesis that treadmill training will improve
      peak fitness, while lowering the energy cost of hemiparetic gait in chronic
      stroke patients. DESIGN: Noncontrolled exercise intervention study with repeated
      measures analysis. SETTING: Hospital-based senior exercise research center.
      PARTICIPANTS: Twenty-three patients (mean age +/- standard deviation [SD] 67 +/-
      8 yr) with chronic hemiparetic gait after remote (>6 mo) ischemic stroke.
      INTERVENTION: Three 40-minute sessions of treadmill exercise weekly for 6 months.
      MAIN OUTCOME MEASURES: Peak exercise capacity (VO2peak) and rate of oxygen
      consumption during submaximal effort treadmill walking (economy of gait) by open
      circuit spirometry and ambulatory workload capacity before and after 3 and 6
      months of training. RESULTS: Patients who completed 3 months of training (n = 21)
      increased their VO2peak +/- SD from 15.4 +/- 2.9 mL x kg(-1) x min(-1) to 17.0 +/
      4.4 mL x kg(-1) x min(-1) (p <.02) and lowered their oxygen demands of
      submaximal effort ambulation from 9.3 +/- 2 mL x kg(-1) x min(-1) to 7.9 +/- 1.5
      mL x kg(-1) x min(-1) (p =.002), which enabled them to perform the same constant
      load treadmill task using 20% less of their peak exercise capacity (62.3% +/-
      17.2% vs 49.9% +/- 19.3%, p <.002). Gains in VO2peak and economy of gait
      plateaued by 3 months, while peak ambulatory workload capacity progressively
      increased by 39% (p <.001) over 6 months. CONCLUSIONS: Treadmill training
      improves physiologic fitness reserve in chronic stroke patients by increasing
      VO2peak while lowering the energy cost of hemiparetic gait, and increases peak
      ambulatory workload capacity. These improvements may enhance functional mobility
      in chronic stroke patients.

PMID- 11441373
TI  - Impact of comprehensive day treatment on societal participation for persons with
      acquired brain injury.
AB  - OBJECTIVES: To evaluate comprehensive day treatment (CDT) for survivors of brain
      injury by time since injury and to identify outcome predictors. DESIGN: Before
      and after. SETTING: Rehabilitation center. PARTICIPANTS: Ninety-six program
      graduates; 17 dropouts with acquired brain injury. INTERVENTIONS: Comprehensive
      Day Treatment Program: daily group sessions to build cognitive and behavioral
      skills through a transdisciplinary approach, supportive feedback, and a variety
      of therapeutic modalities. Obtained outcome measures before and after the
      program, and at 1-year follow-up. MAIN OUTCOME MEASURES:  OUTCOME: Independent
      living status, vocational independence scale at program end and 1-year follow-up;
      and Rasch-analyzed Mayo-Portland Adaptability Inventory (MPAI-22) and goal
      attainment scaling (GAS) at program end. PREDICTORS: age, education, severity of
      initial injury, time since injury, and preadmission MPAI-22. RESULTS: Significant
      goal achievement on GAS and improvement on MPAI-22; increased societal
      participation at 1-year follow-up for those treated postacutely and many years
      after injury: 72% of graduates living independently; 39% working independently,
      10% in transitional placements, and 18% in supported or volunteer work. Long-term
      outcomes were modestly related linearly to preadmission MPAI-22 and nonlinearly
      to time since injury. CONCLUSIONS: CDT improves societal participation even among
      persons with a long history of limited participation after brain injury. This de
      facto extended baseline analysis indicates the effectiveness of CDT and paves the
      way for randomized control trials of active treatment components. Relationships
      of predictors to outcomes are not sufficiently strong for patient selection. More
      effective interventions for vocational reintegration are needed for those most
      severely disabled after brain injury.

PMID- 11441374
TI  - Open-label study of donepezil in traumatic brain injury.
AB  - OBJECTIVE: To determine preliminarily whether donepezil will improve memory,
      behavior, and global function after chronic traumatic brain injury (TBI). DESIGN:
      Sixteen-week open-label study. SETTING: Outpatient TBI rehabilitation program.
      PATIENTS: Four patients with chronic, severe TBI. INTERVENTIONS: Donepezil 5mg
      daily for 8 weeks followed by 10mg daily for 4 weeks. MAIN OUTCOME MEASURES:
      Memory measures included the Rey Auditory Verbal Learning Test (RAVLT), the
      Complex Figure Test (CFT), items from the Rivermead Behavioural Memory Test
      (RBMT), and a semantic fluency task. The Neuropsychiatric Inventory (NPI)
      evaluated behavior and affect. Function was assessed by using the FIM instrument
      and a clinical global impression of change. RESULTS: On the RAVLT, the mean
      scores for learning and short- and long-term recall improved by 0.4, 1.04, and.83
      standard deviations (SDs) above baseline, respectively. On the CFT, the mean
      scores for short-term recall and long-term recall improved by 1.56 and 1.38 SDs
      above baseline, respectively. A positive trend was observed on the RBMT and on
      the NPI subscales. CONCLUSIONS: Donepezil may improve some aspects of memory and
      behavior in persons with chronic TBI. Randomized clinical trials are required to
      support these preliminary findings.

PMID- 11441375
TI  - Infrared skin temperature measurement cannot be used to detect myofascial tender
      spots.
AB  - OBJECTIVE: To determine the relationship between skin temperature and pressure
      tolerance in patients with myofascial pain. DESIGN: Blinded, criterion standard.
      SETTING: Community physiatry clinic. PATIENTS: Sixteen consecutive female
      patients with myofascial pain or fibromyalgia with shoulder girdle symptoms above
      the T4 level for at least 3 months. No patient met the exclusion criteria of
      recent trauma to the area or therapy within 48 hours. INTERVENTIONS: Skin
      temperature was measured by using a hand-held infrared thermometer over 36 points
      arranged in a grid on the upper and midtrapezius. Pressure threshold was then
      assessed at each point by using a pressure threshold meter. A second, blinded
      examiner then examined each patient to find any myofascial tender spots and noted
      within which square on the grid they occurred. MAIN OUTCOME MEASURES: The
      correlation between temperature and pressure threshold and the temperature
      differences between tender and nontender areas. RESULTS: A nonsignificant
      correlation of.023 (p =.57) was found between temperature and pressure threshold.
      The mean temperature of the tender spots was 32.1 degrees C. No significant
      difference existed between tender spot temperature and temperature of nontender
      points (32.1 degrees C, p =.653) or contralateral points (32 degrees C, p =.893).
      CONCLUSIONS: Skin temperature, measured with a hand-held infrared thermometer,
      cannot be used to diagnose and follow treatment progress of myofascial tender
      spots, because skin temperature over tender spots does not correlate with
      pressure sensitivity.

PMID- 11441376
TI  - The effects of a lumbar support on repositioning error in subjects with low back
      pain.
AB  - OBJECTIVE: To determine whether a lumbar support improves trunk repositioning
      error (RE), an aspect of proprioception. DESIGN: RE was measured with and without
      a lumbar support. SETTING: Outpatient clinic. PARTICIPANTS: Twenty subjects with
      chronic low back pain (LBP) and 20 control subjects. INTERVENTIONS: Subjects wore
      the lumbar support for 2 hours and then testing was repeated. MAIN OUTCOME
      MEASURES: Standing with legs and pelvis immobilized, subjects moved to a
      predetermined target position and then attempted to replicate the position. The 3
      dimensional position of the trunk was measured with a 3Space Tracker. RE was
      calculated as the absolute difference between the actual target position and the
      subject-perceived target position. Testing was performed with and without a
      lumbar support both before and after wearing the support for 2 hours. RESULTS: In
      subjects with LBP, RE was significantly lower with a support in flexion,
      extension, and right lateral bending. In control subjects, RE was significantly
      lower when wearing the support in left bending only, and RE was significantly
      higher in control subjects after wearing the support for 2 hours. CONCLUSION: A
      lumbar support improves trunk RE. In subjects with LBP, this result was
      significant in the sagittal plane and in right lateral bending, whereas in
      control subjects, it was significant only in left lateral bending.

PMID- 11441377
TI  - Cervicocephalic kinesthetic sensibility in patients with chronic, nontraumatic
      cervical spine pain.
AB  - OBJECTIVE: To investigate cervicocephalic kinesthetic sensibility (head
      repositioning accuracy to subjective straight ahead) in patients with chronic,
      nontraumatic cervical spine pain. DESIGN: A prospective, 2-group, observational
      design. SETTING: An outpatient chiropractic clinic in the United Kingdom.
      PARTICIPANTS: Eleven patients (6 men, 5 women; mean age +/- standard deviation,
      41.1 +/- 13.3 yr; range, 18-55 yr) with chronic, nontraumatic cervical spine pain
      (mean duration, 24 +/- 18 mo), with no evidence of cervical radiculopathy and/or
      myelopathy or any other neurologic disorder. Eleven asymptomatic, unimpaired
      volunteers (5 men, 6 women; mean age, 39.3 +/- 10.3 yr; range, 28-54 yr) with no
      history of whiplash or other cervical spine injury or pain served as controls.
      MAIN OUTCOME MEASURES: Cervicocephalic kinesthetic sensibility was investigated
      by testing the ability of blindfolded participants to relocate accurately the
      head on the trunk, to a subjective straight-ahead position, after a near-maximal
      active movement of the head in the horizontal or vertical plane. The active
      cervical range of motion and the duration and intensity of neck pain were also
      recorded. RESULTS: Mann-Whitney U testing indicated that the patient (P) group
      was no less accurate in head repositioning than the control (C) group for all
      movement directions except flexion (median global positioning error [95%
      confidence interval], P = 5.7 degrees [5.03-9.10], C = 4.2 degrees [3.17-5.32]; p
      <.05). CONCLUSIONS: Nontraumatic neck pain patients show little evidence of
      impaired cervicocephalic kinesthetic sensibility. These results contrast with
      studies of chronic cervical pain patients in which the origin was not controlled
      or involved a cervical whiplash injury.

PMID- 11441378
TI  - Clock drawing, clock copying, and physical abilities in geriatric rehabilitation.
AB  - OBJECTIVES: To determine whether clock drawing and clock copying assess domains
      that are critical for successful rehabilitation and to evaluate the use of these
      tasks in predicting physical abilities during rehabilitation. DESIGN:
      Observational survey study of geriatric cohorts. SETTING: Inpatient university
      hospital rehabilitation unit. PATIENTS: A total of 172 urban geriatric
      rehabilitation patients with orthopedic, neurologic, or medical diagnoses. MAIN
      OUTCOME MEASURES: Clock drawing and copying, FIM instrument, Mattis Dementia
      Rating Scale, and Neurobehavioral Cognitive Status Examination. RESULTS: Clock
      drawing and copying correlated highly with other measures of general cognitive
      ability. Classifying patients according to established cutoffs on clock drawing
      and copying revealed that patients with cognitive impairment had poorer physical
      abilities at discharge. CONCLUSION: Clock drawing can be used as a brief
      screening measure to determine cognitive integrity. Clock copying can yield
      valuable information about geriatric patients' potential acute rehabilitation
      course and discharge status.

PMID- 11441379
TI  - Precision and accuracy of computed tomography foot measurements.
AB  - OBJECTIVE: To test the accuracy and precision of computed tomography (CT) imaging
      for describing the 3-dimensional structure of the foot in patients with diabetes
      mellitus and peripheral neuropathy. DESIGN: Experimental, test-retest. SETTING:
      Clinical CT scanner at a local hospital. SPECIMENS: Two tissue-equivalent
      phantoms and 6 cadaver feet. MAIN OUTCOME MEASURES: Measurements taken from CT
      data of phantoms and cadaver feet were compared with physical (caliper)
      measurements. The feasibility of creating a computer-aided design/rapid
      prototyping 3-dimensional model from CT data was assessed by using 1 cadaver
      foot. RESULTS: No bias was found for phantom or cadaver CT measurements compared
      with caliper measurements. The mean difference between repeat scans of cadaver
      feet (1 observer) was 0.1 +/- 0.8 mm and between observers, 0.4 +/- 0.8 mm.
      Comparing caliper measurements of the rapid prototype model and actual foot
      measurements revealed an error of 0.3 +/- 0.4 mm. CONCLUSION: CT-based 3
      dimensional imaging produced accurate and precise foot measurements, enabling
      description of internal and external structures. This capability will be coupled
      with plantar pressure measurements to improve our understanding and treatment of
      foot ulcers in people with diabetes.

PMID- 11441380
TI  - Clenbuterol in the prevention of muscle atrophy: a study of hindlimb-unweighted
      rats.
AB  - OBJECTIVE: To determine whether the administration of clenbuterol, a beta2
      adrenergic agonist, prevents loss of muscle mass during a period of imposed
      inactivity. DESIGN: Randomized trial. SETTING: Basic laboratory research.
      ANIMALS: Thirty Fischer 344 Brown Norway F1 Hybrid rats, 12 and 30 months of age.
      INTERVENTIONS: The rats were randomly assigned to a control group, or to 1 of 2
      experimental groups: hindlimb unweighted for 2 weeks (HU-2), or hindlimb
      unweighted with daily injections of clenbuterol for 2 weeks (HU-2Cl). MAIN
      OUTCOME MEASURES: Muscle mass weighed in milligrams and single fiber cross
      sectional area histochemically evaluated. RESULTS: In both age groups, the HU-2
      animals had greater muscle atrophy (decrease in muscle mass) in the soleus muscle
      than the extensor digitorum longus (EDL) muscle. In the HU-2Cl groups, the
      decline in muscle mass of both the soleus and EDL muscles was attenuated by about
      4% to 20%. In the HU-2 group, single fiber cross-sectional area decreased for
      both fiber types (type I, 20%-40%; type II, 37%-50%) in both age groups.
      Clenbuterol retarded the inactivity-induced decline in single fiber cross
      sectional area by 12% to 50%. In the EDL muscles of the HU-2Cl group, we found
      hypertrophy in both fiber types in the 30-month-old animals and in type I fibers
      in the 12-month-old animals. CONCLUSIONS: Clenbuterol attenuated the decrease in
      muscle mass and single fiber cross-sectional area in both age groups. By
      preventing the loss of muscle mass, clenbuterol administered early in
      rehabilitation may benefit severely debilitated patients imposed by inactivity.
      The attenuated muscle atrophy found with clenbuterol in the present study
      provides cellular evidence for the reported change in muscle strength after its
      administration after knee surgery. Thus, the administration of clenbuterol may
      lead to a more rapid rate of rehabilitation.

PMID- 11441381
TI  - The lumbrical provocation test in subjects with median inclusive paresthesia.
AB  - OBJECTIVE: To investigate the value of the Lumbrical Provocation Test (LPT) in
      predicting carpal tunnel syndrome (CTS) among patients with symptoms suspicious
      for CTS. DESIGN: Prospective unigroup technique with blinded comparison of a
      clinical diagnostic test with 2 commonly used methods of diagnosing CTS:
      electrodiagnosis and a hand diagram. SETTING: Outpatient veterans referred by a
      heterogeneous group of specialists and generalists to a Veterans Affairs medical
      center electrodiagnostic laboratory. PATIENTS: Ninety-six consecutive patients
      who were referred to the electrodiagnostic laboratory with median inclusive
      paresthesia were evaluated. INTERVENTIONS: LPT: hold hand as fist for 1 minute
      (to evaluate changes in paresthesia); electrodiagnostic evaluations: median and
      ulnar mixed nerve, antidromic sensory, and motor latencies; and hand symptom
      diagram to describe pain. MAIN OUTCOME MEASURES: Evaluation of symptoms of
      paresthesia (with or without pain) inclusive of the median nerve distribution
      distal to the wrist. Prevalence sensitivity, specificity, and positive and
      negative predictive value of LPT, and electrodiagnosis, and hand diagram tests.
      RESULTS: Compared with the findings obtained with electrodiagnosis, the
      sensitivity of the LPT was.37; specificity,.71; positive predictive value,.59;
      and negative predictive value,.50. Compared with the findings obtained with the
      use of the hand diagram as a clinical measure, the sensitivity of the LPT was.43,
      specificity,.71, positive predictive value,.59, and negative predictive
      value,.56. CONCLUSION: The LPT has minimal use in predicting CTS in patients with
      median inclusive paresthesia compared with 2 commonly used methods of diagnosing
      CTS.

PMID- 11441382
TI  - Measuring leg-length discrepancy by the "iliac crest palpation and book
      correction" method: reliability and validity.
AB  - OBJECTIVE: To determine the reliability and validity of a clinical measurement of
      leg-length discrepancy (LLD), by using the iliac crest palpation and book
      correction (ICPBC) method. DESIGN: Intra- and interrater reliability and validity
      determinations. SETTING: Rehabilitation center. PARTICIPANTS: Thirty-four healthy
      subjects, none of whom had an apparent LLD, as determined by iliac crest
      palpation. INTERVENTIONS: We induced a simulated LLD (7-53 mm) for each subject.
      To measure the LLD, the examiner performed the ICPBC method by palpating the
      iliac crests and correcting identified differences with a book opened to the
      required number of pages. The thickness of the book correction was measured. MAIN
      OUTCOME MEASURES: Reliability LLD measurement (n = 20), by using the ICPBC method
      to measure the LLD; construct validity (n = 34), comparing ICPBC measurement with
      the extent of the induced LLD; and concurrent validity (n = 14), the difference
      in heights of the superior aspect of the femoral heads from standing radiographs.
      RESULTS: The intraclass correlation coefficients (ICCs) for the intrarater and
      interrater reliabilities were.98 and.91, respectively. The ICCs for the construct
      and concurrent validities were.62 and.76, respectively. The ICPBC method
      underestimated the induced LLD by a mean difference +/- standard deviation of 3.8
      +/- 10.3mm (p =.055) and the radiologic measure by 5.1 +/- 8.6 mm (p =.043).
      CONCLUSIONS: The ICPBC technique for measuring LLD is highly reliable and
      moderately valid. When there is no history of pelvic deformity and the iliac
      crests can be readily palpated, we recommend using iliac crest palpation to
      detect LLD, and the book correction to quantify it.

PMID- 11441383
TI  - Osteogenesis imperfecta in childhood: perceived competence in relation to
      impairment and disability.
AB  - OBJECTIVES: To examine the perceived competence of children with different types
      of osteogenesis imperfecta (OI) and to investigate the possible relationships
      between their perceived competence and impairment parameters. DESIGN: Cross
      sectional study. SETTING: National referral center (hospital) for the treatment
      of children with OI. PATIENTS: Forty children with OI (type I = 17; type III =
      11; type IV = 12) with a mean age +/- standard deviation of 12.6 +/- 3.2 years.
      INTERVENTIONS: Measured joint range of motion (ROM) in the upper extremities
      (UEs), and lower extremities (LEs), muscle strength, functional skills,
      ambulation, and perceived competence. MAIN OUTCOME MEASURES: Joint ROM in UE and
      LE; muscle strength (using the manual muscle testing criteria of the Medical
      Research Council); functional skills using the Pediatric Evaluation of Disability
      Inventory in 3 domains (self-care, mobility, social function). Ambulation
      (according to Bleck and classified as nonwalking, therapy walking, household
      walking, neighborhood walking, community walking with or without the use of
      crutches), and perceived competence (using the Harter Self-Perception Profile for
      Children, which was cross-culturally validated for Dutch children). RESULTS: In
      children with type I, joint ROM and muscle strength were almost comparable to the
      healthy population. In children with type III, a severe decrease in joint ROM was
      measured, especially in the LEs, and muscle strength was severely decreased in
      the UEs and LEs. In children with type IV, joint ROM and muscle strength
      decreased, especially in the LEs. In all types, fairly to strongly positive
      perceived competence was measured except for fairly negative perceived competence
      in the athletic performance subscale in type I and a fairly negative perceived
      competence in the romance subscale in type III. No correlations were found
      between (1) joint ROM and athletic performance and physical appearance, (2)
      muscle strength and athletic performance or physical appearance, or (3) the
      functional skills, concerning self-care and mobility, with the subscales of the
      perceived competence. CONCLUSIONS: Although joint ROM, muscle strength, and
      functional and walking ability were related to the severity of the disease and
      differed significantly between the different types of OI, overall perceived
      competence in children with OI was fairly to strongly positive, without
      significant differences between the different types of OI.

PMID- 11441384
TI  - Quality of life after spinal cord injury caused by gunshot.
AB  - OBJECTIVE: To determine what effect gunshot-caused spinal cord injury (SCI) has
      on self-reported quality of life (QOL) and on the frequency of pain sufficient to
      interfere with day-to-day activities. DESIGN: Follow-up, case-control design.
      SETTING: Analysis of data obtained from the (US) National Spinal Cord Injury
      Statistical Center from 18 funded Spinal Cord Injury Model Systems. PARTICIPANTS:
      Individuals with traumatic onset SCI (n = 1901). From these, 111 persons with
      gunshot-caused SCI were matched to persons with nongunshot SCI. MAIN OUTCOME
      MEASURES: Satisfaction with Life Scale (SWLS), the Craig Handicap Assessment and
      Reporting Technique (CHART), Medical Outcomes Study Short-Form Health Survey (SF
      12), and an individual pain item from the SF-12. RESULTS: No between-group
      differences were found on any of the QOL outcome measures. In contrast, those
      with SCI caused by gunshot reported that pain more frequently interfered with day
      to-day activities than the matched comparison group. CONCLUSIONS: SCI caused by
      gunshot appears largely unrelated to QOL, after controlling for demographic and
      medical characteristics associated with this group. Gunshot as a mechanism of SCI
      may place individuals at an increased risk of subsequent development of pain that
      interferes with activities of daily living.

PMID- 11441385
TI  - Glenohumeral subluxation, scapula resting position, and scapula rotation after
      stroke: a noninvasive evaluation.
AB  - OBJECTIVES: To determine whether scapular downward tilt (ScDT) and dynamic
      scapular lateral rotation (ScLR) in subjects with and without stroke is
      associated with subluxation, and to prove the reliability of a Scapula Locator
      System in an elderly population. DESIGN: Repeated measures of ScLR by 2
      observers. SETTING: Outpatient rehabilitation department of a district general
      hospital. PARTICIPANTS: To test device reliability, 5 healthy men (mean age +/-
      standard deviation, 72 +/- 5 yr). To test scapula position, 30 stroke patients
      (19 men, 11 women; mean age, 73 +/- 6 yr) and 15 healthy controls (12 men, 3
      women; mean age, 62 +/- 6 yr). INTERVENTIONS: The control subjects' ScDT was
      compared with stroke subjects' ScDT after stratification according to 3 patterns
      of ScLR symmetry and the presence of palpable glenohumeral subluxation. MAIN
      OUTCOME MEASURES: For device reliability, 3-way analysis of variance. For scapula
      position, triangulated location by Scapula Locator System of acromion, inferior
      angle, and root of the scapular spine; then measurement of scapula motion to
      determine symmetry, lag, or lead. RESULTS: The inter- and intraobserver
      reliability of the Scapula Locator System device was high (1% of variance each).
      Normal ScDT was positive (left side: 10.94 degrees +/- 2.62 degrees; right side:
      9.69 degrees +/- 4.36 degrees ), indicating a downward-facing glenoid fossa. This
      finding was unchanged by stroke (10.46 degrees +/- 2.42 degrees ). All controls
      and 16 stroke subjects had symmetry between shoulders for ScLR rate and ScDT. Two
      other patterns (p <.01) of ScLR were found after stroke: 8 subjects had a slower
      rate of affected arm ScLR (lag) with a correspondingly greater ScDT on the
      affected side (2.61 degrees +/- 6.7 degrees ); 6 subjects had a faster rate of
      affected arm ScLR (lead) but with an upward-facing glenoid fossa on the affected
      side (ScDT: -11.84 degrees +/- 8.48 degrees ). No significant inter- or
      intrasubject difference in ScDT existed in the 6 cases of glenohumeral
      subluxation. CONCLUSIONS: The scapula normally tilts downward with or without
      stroke. The effect of stroke is similar on tonic (ScDT) and phasic (ScLR) control
      of scapula position. Subluxation is not linked with a particular scapular resting
      position after stroke.

PMID- 11441386
TI  - Arm ability training for stroke and traumatic brain injury patients with mild arm
      paresis: a single-blind, randomized, controlled trial.
AB  - OBJECTIVE: To test the efficacy of the arm ability training (AAT) on a sample of
      patients with central arm paresis after traumatic brain injury (TBI) or stroke.
      DESIGN: Single-blind, randomized, controlled trial. SETTING: Inpatient
      rehabilitation center. PATIENTS: Consecutive sample of 74 patients of whom 60 (45
      with stroke, 15 with TBI) completed the study; 37 patients received a 1-year
      follow-up. INTERVENTION: Daily AAT with (n = 20) or without (n = 20) knowledge of
      results, or no AAT (n = 20) during a 3-week intervention period. MAIN OUTCOME
      MEASURES: Summary time scores of the Test Evaluant les Membres superieurs des
      Personnes Agees (TEMPA)-a test of upper extremity function with daily function
      like activities (focal disability)-and kinematic analysis of aimed movements.
      RESULTS: Patients with AAT realized superior improvement as compared with
      controls. Mean improvement in the time needed to perform (1) all TEMPA tasks was
      41.4 versus 12.8 seconds (p =.0012); (2) unilateral TEMPA tasks, 16.5 versus 4.2
      seconds (p =.0036); and (3) the ballistic component of aimed movements, 96 versus
      20ms (p =.0115). Knowledge of result did not substantially modify these effects.
      A functional benefit existed at 1-year follow-up. CONCLUSION: The AAT reduces
      focal disability among stroke and TBI patients with mild central arm paresis.

PMID- 11441387
TI  - Functional magnetic stimulation facilitates colonic transit in rats.
AB  - OBJECTIVE: To investigate the effect of functional magnetic stimulation (FMS) on
      colonic transit in rats. DESIGN: Experimental. SETTING: Functional magnetic
      stimulation laboratory in a Veterans Administration health care system. ANIMALS:
      Twenty-four female Wistar rats, divided into an experimental group and a control
      group. INTERVENTIONS: All rats had technetium 99m (Tc 99m) infused through a
      cecal catheter to assess colonic transit times. FMS was performed over the
      cervical region; a figure of 8 magnetic coil was used in the experimental group.
      The colon was removed and sectioned into 10 segments, and a stool sample was
      taken in both groups. MAIN OUTCOME MEASURES: Distribution of radioactivity within
      the large intestine and stool were measured. RESULTS: Geometric center
      calculations showed significant differences (p <.001) between the control group
      and the experimental group when the distribution of radioactivity along the colon
      was measured. The percentage of Tc 99m recovered from the stool in the
      experimental group was significantly higher than the percentage recovered from
      the control group. CONCLUSION: FMS facilitates colonic transit in a rat model.

PMID- 11441388
TI  - Characterization of the human quadriceps muscle in active elders.
AB  - OBJECTIVE: To compare muscle activation deficits and muscle physiology in older
      versus younger adults. DESIGN: A maximal volitional isometric contraction of the
      quadriceps muscle with burst-superimposition was used to assess strength and
      activation. In addition, force-frequency testing during fresh, fatigue, and
      recovery conditions and electrically elicited fatigue testing were performed.
      SETTING: Muscle performance laboratory. PATIENTS: Healthy, active young (age
      range, 20-28 yr) and older (age range, 66-83 yr) subjects. MAIN OUTCOME MEASURES:
      Torque production, activation of the quadriceps, F50 values from the force
      frequency relationships (frequency at which 50% of the maximum normalized force
      is produced), and the average amount of fatigue. RESULTS: Older subjects were
      weaker (574.4 +/- 156 N) than younger subjects (900.9 +/- 295 N) and had
      significantly greater deficits in central activation in the quadriceps muscles
      (elderly = 95.5% activation; younger = 98.1% activation). The force-frequency
      curves for the elderly were to the left of the younger subjects for all 3 testing
      conditions. Aged muscles fatigued to the same extent as younger muscle (young =
      49.8% +/- 2.6%, elderly = 51.1% +/- 2.8%). CONCLUSIONS: These results can be used
      to modify high-intensity strength training protocols designed to optimize
      sustainable strength gains in the elderly during rehabilitation.

PMID- 11441389
TI  - Swallowing in myotonic muscular dystrophy: a videofluoroscopic study.
AB  - OBJECTIVES: (1) To determine how swallow function in patients with myotonic
      muscular dystrophy (MD) differs from that of healthy controls, (2) to identify
      the contributors to and predictors of improvement, and (3) to evaluate strategies
      that facilitate swallowing. DESIGN: Observational. SETTING: University medical
      center. PARTICIPANTS: Eighteen adults with myotonic MD (age range, 24-58 yr) and
      60 healthy adult control subjects (age range, 18-73 yr). INTERVENTIONS: Swallow
      facilitation strategies. MAIN OUTCOME MEASURES: Between-group comparisons of mean
      bolus transit times, onsets of swallow gestures, and displacement measures
      obtained by dynamic lateral view videofluoroscopy. RESULTS: The MD patients'
      bolus transit times were significantly longer, and onsets of some swallow
      gestures were significantly delayed. Upper esophageal sphincter opening was
      prolonged (myotonic MD,.61 +/-.13s; control,.5 +/-.11s). Hyoid displacement was
      significantly less in men with myotonic MD (1.9 +/-.05 cm) than in male controls
      (2.4 +/-.68 cm); this difference was not observed between control and myotonic
      women. Of particular importance was the markedly reduced pharyngeal constriction
      found in the MD group. CONCLUSIONS: Weakness associated with the disease, as
      opposed to myotonia, was the most significant contributor to impairment. Persons
      at risk for aspiration may be identified by a measure of pharyngeal area.
      Selected strategies to facilitate pharyngeal clearing are worthwhile.

PMID- 11441390
TI  - Needling therapies in the management of myofascial trigger point pain: a
      systematic review.
AB  - OBJECTIVE: To establish whether there is evidence for or against the efficacy of
      needling as a treatment approach for myofascial trigger point pain. DATA SOURCES:
      PubMed, Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, AMED, and CISCOM
      databases, searched from inception to July 999. STUDY SELECTION: Randomized,
      controlled trials in which some form of needling therapy was used to treat
      myofascial pain. DATA EXTRACTION: Two reviewers independently extracted data
      concerning trial methods, quality, and outcomes. DATA SYNTHESIS: Twenty-three
      papers were included. No trials were of sufficient quality or design to test the
      efficacy of any needling technique beyond placebo in the treatment of myofascial
      pain. Eight of the 10 trials comparing injection of different substances and all
      7 higher quality trials found that the effect was independent of the injected
      substance. All 3 trials that compared dry needling with injection found no
      difference in effect. CONCLUSIONS: Direct needling of myofascial trigger points
      appears to be an effective treatment, but the hypothesis that needling therapies
      have efficacy beyond placebo is neither supported nor refuted by the evidence
      from clinical trials. Any effect of these therapies is likely because of the
      needle or placebo rather than the injection of either saline or active drug.
      Controlled trials are needed to investigate whether needling has an effect beyond
      placebo on myofascial trigger point pain.

PMID- 11441391
TI  - Complex regional pain syndrome (type I) after electrical injury: a case report of
      treatment with continuous epidural block.
AB  - A 26-year-old man presented with severe complex regional pain syndrome type I of
      the affected limb after a work-related electrical injury. He suffered causalgia
      like pain with no electrodiagnostic evidence of nerve injury. Early steroid and
      analgesic regimens did not adequately relieve these symptoms. His symptoms were
      temporarily relieved several times with stellate ganglion blocks. The patient
      underwent a cervical epidural block with a local anesthetic as well as a narcotic
      agonist over a 4-day period, which resulted in prompt, remarkable pain relief.
      Vocational rehabilitation was instituted as the pain subsided.

PMID- 11441392
TI  - Carcinoid tumor mistaken for persistent neurogenic bowel symptoms in a patient
      with paraplegia: a case report.
AB  - Neurogenic bowel in spinal cord injury (SCI) can present with constipation and
      diarrhea as ongoing problems. Usually, these manifestations are adequately
      controlled with modification in the bowel program. When these symptoms persist,
      other causes should be considered. This case report describes a jejunal carcinoid
      tumor with colonic extension that was diagnosed in a paraplegic patient with
      persistent constipation and diarrhea. A 39-year-old man sustained a T1 paraplegia
      with neurogenic bowel and bladder dysfunction from a gunshot wound. His bowels
      were initially managed adequately with digital disimpaction. Over the next 8
      years, he had intermittent constipation that was managed with the addition of
      various suppositories. He then developed progressively worsening constipation,
      and other gastrointestinal (GI) symptoms. Although his symptoms initially
      resolved with medical management, the constipation worsened. Upper endoscopy
      revealed a submucosal bulge in the duodenal bulb. A month later, gallstones were
      found on renal ultrasound performed to evaluate recurrent urinary tract
      infections. He underwent cholecystectomy, but his GI symptoms persisted over the
      next several months. Repeat upper endoscopy subsequently revealed an ulcerated
      tumor at the duodenojejunal flexure. An upper-GI scan with small bowel follow
      through showed a proximal jejunal mass. The patient underwent laparotomy with
      resection of the mass. Final pathologic diagnosis was malignant carcinoid tumor.
      This case shows the importance of entertaining other clinical entities in
      patients with SCI when constipation and diarrhea persist despite adequate
      management.

PMID- 11441393
TI  - Effect of rearfoot orthotics on postural sway after lateral ankle sprain.
AB  - OBJECTIVE: To investigate the effects of different rearfoot orthotics on postural
      sway during unilateral stance after lateral ankle sprain. DESIGN: Repeated
      measures 3-factor analysis of variance on postural sway length and velocity in
      the frontal and sagittal planes with factors being stance leg (injured,
      uninjured), session (within 3 d, 2 wk, 4 wk postinjury), and condition (6
      orthotic conditions). SETTING: University biomechanics laboratory. PATIENTS:
      Fifteen collegiate athletes with acute, unilateral first- or second-degree
      lateral ankle sprain. INTERVENTIONS: Balance testing was performed under 6
      conditions: (1) shoe only, (2) molded Aquaplast orthotic, (3) lateral heel wedge,
      (4) 7 degrees medially posted orthotic, (5) 4 degrees laterally posted orthotic,
      and (6) neutral orthotic. MAIN OUTCOME MEASURES: Postural sway length and
      postural sway velocity in the frontal and sagittal planes. RESULTS: Significant
      main effects were found for side and session, but not orthotic condition, for all
      4 dependent variables. Postural sway length and velocity were greater on the
      injured limbs as compared with the uninjured limbs during the first 2 sessions
      but not during the third session. None of the orthotics significantly reduced
      postural sway compared with the shoe-only condition after lateral ankle sprain.
      CONCLUSIONS: Rearfoot orthotics, irrespective of design or posting, were
      ineffective at improving postural sway after lateral ankle sprain.

PMID- 11441394
TI  - Was hamstring muscle stiffness measured?

PMID- 11441397
TI  - Ergonomics of hand-assisted laparoscopic surgery.
AB  - Hand-assisted laparoscopic surgery (HALS) facilitates complex or advanced
      laparoscopic operations without appreciable loss of the advantages of the total
      laparoscopic approach. The internal hand enables atraumatic exposure and
      stretching of tissue planes, finger dissection, restores palpation of internal
      organs and structures, and provides a rapid and effective means of hemostasis.
      Particularly during complex surgery performed on the liver and pancreas, this
      ability to control bleeding by placing pressure between the index finger and
      thumb reduces the stress on the surgeon. HALS does, however, carry a number of
      ergonomic problems that are consequent on the encroachment of the hand and device
      on the workspace. It also imposes an awkward lordotic stance, hence back and
      shoulder strain on the surgeon. These problems can be resolved by further
      development of the hand-access devices and also with modifications of existing
      laparoscopic instruments, or the design and development of HALS-dedicated
      specific instrumentation. Further progress and increased scope of HALS will only
      be achieved with designs based on ergonomic research.

PMID- 11441398
TI  - Hand-assisted laparoscopic surgery in the United States: an overview.
AB  - Hand-assisted laparoscopic surgery (HALS) was developed to bridge the gap between
      open surgery and advanced laparoscopic surgery. Advantages of the hand in the
      abdomen include tactile feedback, the ability to palpate, blunt dissection, organ
      retraction, control of bleeding, and rapid organ removal. There are 3
      commercially available devices in the United States, as well as a fourth in
      Europe and a fifth in Japan. Uses for HALS include procedures requiring intact
      specimen removal, complex laparoscopic procedures, preventing open conversion,
      and overcoming a technical obstacle. HALS procedures, such as esophagectomy,
      gastrectomy, hepatectomy, pancreatectomy, splenectomy, bariatric surgery,
      colectomy, nephrectomy, hysterectomy, and aortobifemoral bypass, have all been
      reported in the literature. Improvement in instrumentation, specifically with
      newer generation devices, will allow HALS to become more popular. We advocate the
      use of HALS specifically for laparoscopic colectomy, laparoscopic splenectomy for
      massive splenomegaly, and for living-related donor nephrectomy.

PMID- 11441399
TI  - Laparoscopic hand-assisted hepatic surgery.
AB  - At Ninewells Hospital, we have changed from total to hand-assisted laparoscopic
      hepatic resections. We report here our initial experience on 10 anatomic hepatic
      resections with good outcome, and 1 with a significant postoperative complication
      (fall in the hemoglobin) requiring laparotomy. All resections were undertaken by
      using the Omniport device (Advanced Surgical Concepts, Dublin, Ireland). The hand
      assisted laparoscopic surgery (HALS)-Omniport approach has also been used
      selectively in 5 patients undergoing in situ ablation for bilateral metastatic
      disease with lesions not easily accessible to the total laparoscopic approach,
      ie, situated in the posterior and inferior segments of the right liver. The HALS
      approach has several advantages; it facilitates and expedites the procedure,
      reduces the stress factor to the surgeon, greatly improves exposure, and provides
      an immediate and efficient control of bleeding vessels with the internal hand.
      The Omniport device, which essentially consists of a handcuff with a spiral
      inflatable valve, enables withdraw and reinsertion of the hand without loss of
      pneumoperitoneum during the procedure. The device was effective in maintaining
      pneumoperitoneum in all cases. All operations were completed with the HALS
      approach.

PMID- 11441400
TI  - Hand-assisted laparoscopic pancreatic resection.
AB  - The extent of reported laparoscopic pancreatic resections vary from enucleation
      to pancreaticoduodenectomy. Nevertheless, most patients with pancreatic disease
      who require resection are still treated with a traditional approach.
      Technological advancements in recent years may play an important role for the
      future diffusion of laparoscopic pancreatectomy. In hand-assisted laparoscopic
      surgery, the surgeon inserts a hand into the abdomen through a small laparotomy
      while pneumoperitoneum is maintained, and uses the hand to assist with
      dissection, palpation and retraction, control of blood vessels, manipulation of
      organs, and removal of the specimen. We present a review of our experience and of
      the world literature on hand-assisted laparoscopic pancreatic resection. Based on
      the first encouraging results, we believe that the hand-assisted technique should
      allow for substantial advantages to laparoscopic pancreatic surgery in the
      future.

PMID- 11441401
TI  - Hand-assisted laparoscopic splenectomy.
AB  - Hand-assisted laparoscopic surgery (HALS) permits recovery of the tactile
      sensation and facilitates manipulation of solid organs. Our preliminary
      experience in laparoscopic splenectomy (LS) shows its advantages, with a
      substantial reduction of operative time, while maintaining the advantages of a
      less aggressive surgical approach. The role of HALS in cases of splenomegaly or
      trauma seems to be clear. It can also be considered as an alternative to
      conventional conversion in cases of intraoperative complications or unclear
      anatomy. The role of HALS for normal-sized spleens is more controversial because
      there is a well-systematized, conventional LS technique available, which is
      followed by optimal clinical outcome LS in hands of a skilled surgeon.

PMID- 11441402
TI  - Hand-assisted gastroesophageal surgery.
AB  - Hand-assisted laparoscopic surgery (HALS) has been shown to be an effective tool
      when performing advanced laparoscopic procedures. The hand-assist device restores
      tactile feedback, facilitates retraction and dissection, and can be a successful
      alternative to open conversion. HALS is a valuable resource when performing
      complex gastroesophageal operations, including gastrectomy, esophagectomy, and
      bariatric surgery. The aim of this review is to familiarize the laparoscopic
      surgeon with the use of HALS when performing these technically demanding
      procedures.

PMID- 11441403
TI  - Hand-assisted laparoscopic bariatric surgery.
AB  - Bariatric surgery implies a major life-long rearrangement of the gastrointestinal
      tract to obtain a controlled weight reduction in a severe but nonmalignant
      disease. Obesity poses a special challenge to the laparoscopic surgeon.
      Laparoscopy is known to facilitate the perioperative phase for the patient, but
      is technically difficult to perform in morbidly obese subjects. Hand-assistance
      adds extra control in demanding procedures, and Hand-port systems for use in the
      thick abdominal wall are now available. Here we review the role of hand-assisted
      laparoscopy for common bariatric procedures and describe our technique for Hand
      assisted laparoscopic Roux-en-Y Gastric bypass. Hand-assistance might be the well
      blended mix for complex laparoscopic procedures in bariatric work, especially for
      surgeons working outside highly specialized laparoscopic centers.

PMID- 11441404
TI  - Hand-assisted laparoscopic colorectal surgery.
AB  - Hand-assisted laparoscopic surgery is a newly developed technique. It involves
      the intra-abdominal placement of a hand or forearm through a mini laparotomy
      incision while pneumoperitoneum is maintained. This way, the hand can be used as
      in an open procedure to palpate organs or tumours, reflect organs atraumatically,
      retract structures, identify vessels, dissect bluntly along a tissue plain, and
      provide finger pressure to bleeding points while proximal control is achieved.
      Additionally this approach is more economical than a totally laparoscopic
      approach, reducing both the number of laparoscopic ports and number of
      instruments required. Some advocates of the technique claim that it is also
      easier to learn and perform than totally laparoscopic approaches, and that there
      may be increased patient safety.

PMID- 11441405
TI  - Laparoscopic and hand-assisted laparoscopic live donor nephrectomy.
AB  - Renal grafts from living donors represent an important source of organs,
      particularly for young patients with chronic renal failure. Laparoscopic donor
      nephrectomy is a relatively new technique, which has the potential to increase
      the pool of available kidney grafts by removing some disincentives to live
      donation. The technique used for left kidney donation at our center, the first to
      introduce laparoscopic live donor nephrectomy in Italy, is described in this
      report. To further reduce warm ischemia time, the kidney is preloaded inside the
      extraction bag and 2 staplers are used to transect the renal artery and vein. The
      spread of the new technique in our country and in the rest of Europe is likely to
      raise the issue of training in laparoscopic surgery for transplant surgeons.

PMID- 11441406
TI  - Hand-assisted laparoscopic abdominal aortic aneurysm repair.
AB  - Hand-assisted laparoscopic aneurysm resection enables the surgeon to use his
      tactile senses while performing a laparoscopic aneurysm repair. Even more complex
      procedures that involve suprarenal clamping of the aorta can be performed by
      using this laparoscopically assisted approach. Twenty-nine laparoscopic patients
      were compared with a control group of 19 patients who were operated on
      conventionally. Transperitoneal hand-assisted laparoscopic aneurysm resection
      with a tube graft or a bifurcated graft was performed. The anastomosis was
      sutured with conventional instruments using the mini-incision as an access. The
      time for laparoscopy did not exceed 40 minutes. The incidence of complications
      did not vary between groups. The mean operating time was 135 minutes in the
      conventional group versus 180 minutes in the minimal invasive group. Intensive
      care stay and postoperative hospital stay were significantly shorter after the
      laparoscopic procedure. An oral diet was resumed significantly earlier, and the
      time until complete recovery was shortened in the miniaccess group. Hand-assisted
      laparoscopic aneurysm resection can be performed safely with operating times
      almost as expeditiously as in open surgery. Because it can be offered to the
      majority of patients with aortic disease, the technique described has distinct
      advantages over a total laparoscopic approach and a less steep learning curve.

PMID- 11441408
TI  - New drug and multimodality combinations in the treatment of advanced non--small
      cell lung cancer.

PMID- 11441409
TI  - Phase III randomized trial of docetaxel in combination with cisplatin or
      carboplatin or vinorelbine plus cisplatin in advanced non--small cell lung
      cancer: interim analysis.
AB  - In the TAX 326 trial, 1,220 chemotherapy-naive patients with advanced or
      metastatic non--small cell lung cancer have been randomized to receive one of
      three regimens: docetaxel 75 mg/m(2) plus cisplatin 75 mg/m(2) every 3 weeks;
      docetaxel 75 mg/m(2) plus carboplatin to an area under the curve of 6 mg/mL x min
      every 3 weeks; or a control arm of vinorelbine 25 mg/m(2) weekly plus cisplatin
      100 mg/m(2) monthly. The treatment and toxicity data presented are based on a
      planned preliminary analysis conducted after 601 patients had been enrolled. The
      median age of patients randomized was 60 years and 73% were male. The majority of
      patients had a Karnofsky score of 80 or greater, two thirds had stage IV disease
      and 35% had three or more sites of organ involvement. While the relative dose
      intensity for docetaxel was 0.97 both when combined with cisplatin and when
      combined with carboplatin, the corresponding figure for vinorelbine was 0.68,
      reflecting the frequent need for dose reduction when combined with cisplatin on
      the schedule used. Hematologic toxicities were tolerable and comparable across
      the three arms of the trial, and the rate of febrile neutropenia was below 5% in
      all cases. The incidence of nonhematologic toxicities also was similar, although
      nausea and vomiting appeared to be less frequent among patients assigned to
      docetaxel plus carboplatin than among patients receiving comparator regimens.
      Semin Oncol 28 (suppl 9):10-14.

PMID- 11441410
TI  - Non-platinum based combination chemotherapy: phase I and II trials of docetaxel
      plus gemcitabine, vinorelbine, or irinotecan.
AB  - Non-platinum combination regimens have been developed for advanced non--small
      cell lung cancer using the novel and active agents docetaxel, gemcitabine,
      vinorelbine, and irinotecan. The aim of these combinations is to equal or exceed
      the survival benefits achieved with cisplatin doublets while minimizing toxicity.
      Of the docetaxel-based combinations, gemcitabine has been the most extensively
      studied. In a 317-patient randomized trial, docetaxel plus gemcitabine achieved a
      response rate of 34%, similar to the 32% response rate seen in patients
      randomized to docetaxel plus cisplatin. One-year survival rates were 38% and 42%,
      respectively. While being equally active, the docetaxel/gemcitabine combination
      was associated with significantly less neutropenia and gastrointestinal adverse
      events than the cisplatin-containing regimen. Phase II trials of docetaxel plus
      vinorelbine have reported response rates of up to 51% and 1-year survival in up
      to 60% of patients without significant peripheral neuropathy. Docetaxel plus
      irinotecan is also active in advanced non--small cell lung cancer and has shown
      similar efficacy to docetaxel plus cisplatin in a randomized trial. The adverse
      event profile of docetaxel/irinotecan is different from that of cisplatin-based
      regimens. Both non-platinum and platinum combination regimens have an important
      role to play in the treatment of non--small cell lung cancer. Semin Oncol 28
      (suppl 9):15-20.

PMID- 11441411
TI  - Weekly docetaxel as a single agent and in combination with gemcitabine in elderly
      and poor performance status patients with advanced non--small cell lung cancer.
AB  - Administering docetaxel weekly at a relatively low dose minimizes
      myelosuppression and reduces nonhematologic toxicities. In a community-based
      phase II trial conducted in 39 elderly or poor performance status patients with
      advanced non--small cell lung cancer, weekly 36 mg/m(2) docetaxel produced a
      response rate of 20%. The response rate was 26% in patients with an Eastern
      Cooperative Oncology Group performance status of 0 or 1. Actual 1-year survival
      was 28% and actuarial 2-year survival was 15%. These results are similar to those
      achieved with other active single agents. The regimen of weekly docetaxel used
      was associated with minimal hematologic toxicity. There were no cases of grade 4
      leukopenia, febrile neutropenia, toxicity-related hospital admissions, or
      treatment-related death. Nonhematologic toxicities were also mild, even in
      performance status 2 patients. In a subsequent phase II trial, a similar group of
      patients received weekly docetaxel at 30 mg/m(2) plus weekly gemcitabine 800
      mg/m(2), both drugs given on days 1, 8, and 15 every 28 days. Preliminary
      analysis of data for the first 41 patients enrolled show an objective response
      rate of 29%, with an additional 45% of patients having stable disease. Although
      26% of patients missed the day 15 dose of gemcitabine and docetaxel because of
      myelosuppression, the combination regimen was generally well tolerated. There
      were no hospitalizations caused by complications of myelosuppression. One patient
      developed bilateral pulmonary infiltrates, possibly treatment-related, and died
      of respiratory failure. Further evaluation of weekly docetaxel-based combinations
      is indicated. Semin Oncol 28 (suppl 9):21-25.

PMID- 11441412
TI  - Integration of new chemotherapeutic agents into chemoradiotherapy for stage III
      non--small cell lung cancer: focus on docetaxel.
AB  - Randomized clinical trials have shown that combinations of chemotherapy plus
      thoracic radiation improve survival compared with radiotherapy alone in stage III
      non--small cell lung cancer (NSCLC). Furthermore, two recent studies have
      concluded that concurrent chemoradiotherapy produces superior results to
      sequential administration. Dependent on the dose and schedule used, chemotherapy
      may contribute by eradicating distant micrometastases by improving local control
      as a radiosensitizer, or through both mechanisms. In general, sequential
      approaches in which full-dose platinum-based chemotherapy precedes thoracic
      radiation or surgery have improved outcome by impacting distant metastases. In
      contrast, concurrent chemoradiotherapy using low-dose cisplatin is reported to
      improve survival by reducing local recurrence without an impact on distant
      failure rates. In view of these observations, chemoradiotherapy strategies
      integrating both radiosensitizing agents and dose levels of chemotherapy
      effective against micrometastases may prove to be most efficacious. Because
      distant metastases remain the major site of failure, it also is likely that more
      effective chemotherapy will be required to further improve the current level of
      response and survival. Fortunately, several newly available chemotherapeutic
      agents are both highly active against NSCLC and are potent radiosensitizers. In
      this report we review recent data regarding integration of new chemotherapeutic
      agents into chemoradiotherapy programs in stage III NSCLC, focusing on trials
      investigating docetaxel. Encouraging results, including those of the Southwest
      Oncology Group trial 9504, suggest that docetaxel will play a major role in the
      future of combined-modality therapy for locally advanced NSCLC. Semin Oncol 28
      (suppl 9):26-32.

PMID- 11441413
TI  - Neoadjuvant chemotherapy with docetaxel in non--small cell lung cancer.
AB  - Based on proven activity and survival benefit in advanced non--small cell lung
      cancer, docetaxel has been introduced into neoadjuvant therapy. In a large, phase
      III randomized trial in 274 stage IIIA and IIIB patients, treatment with an
      induction regimen of 100 mg/m(2) docetaxel for three cycles before definitive
      surgery or radiotherapy was associated with an encouraging trend towards longer
      median survival. Overall 1-year survival was 59% compared with 51% in the control
      group. Docetaxel in the neoadjuvant setting was well tolerated and did not
      compromise later radical local therapy. The incidence of grade (3/4) esophagitis,
      for example, was less than 1% in patients who had had induction docetaxel
      followed by curative radiotherapy. This also was true for pneumonitis.
      Neoadjuvant docetaxel in combination with cisplatin or carboplatin is being
      evaluated in phase II trials which have reported response rates of 66% to 82% and
      rates of complete resection ranging from 69% to 79%. Docetaxel also is being
      investigated in combination with both cisplatin and gemcitabine in phase I/II
      studies. Phase III trials will further define the promising role of docetaxel
      alone and in combination in neoadjuvant therapy. Semin Oncol 28 (suppl 9):33-36.

PMID- 11441415
TI  - History of plasma-product safety.
AB  - The evolution of transfusion or infusion therapies for diseases requiring
      specific protein replacements (e.g., hemophilia A and B and severe combined
      immunodeficiency syndrome) was dramatic over the second half of the 20th century.
      Unfortunately, it was accompanied by extreme manifestations of transfusion
      transmitted diseases, such as human immunodeficiency virus (HIV), hepatitis B,
      and hepatitis C. The milestones of both the replacement therapies and the
      associated diseases are discussed in this presentation, which focuses on the
      technologic advances that resulted in even more "pure" replacement therapies for
      plasma-protein diseases. From donor screening to the development of viral
      attenuation techniques, every facet of production for these products was impacted
      by the exigent push for viral safety created by HIV and hepatitis. Almost
      invariably, this negatively affects total product yield. At the beginning of the
      21st century, success in making plasma products safe from recognized and
      potential pathogens has dramatically increased societal pressures to produce a
      zero-risk, plasma-derived protein therapy. However, past improvements and low
      theoretic risks for future pathogen contamination have increased product cost.
      This is associated with a possible decrease in the overall supply of these plasma
      proteins because of the reduced numbers of acceptable donors and the loss of
      protein from expanded attenuation technology. These impacts and the role of
      dynamic societal and scientific pressures on these decision processes are
      discussed.

PMID- 11441416
TI  - Safety issues affecting hemophilia products.
AB  - Clotting factor concentrates (CFCs) have evolved substantially toward both safety
      from pathogens and overall final purity of the products. The array of product
      types for both factor VIII and factor IX CFCs ranges from so-called intermediate
      purity (containing multiple plasma proteins), very high purity (containing
      chiefly the respective purified clotting protein plus an albumin stabilizer), and
      recombinant CFCs (with or without albumin stabilizers). Each is discussed in the
      context of theoretic safety, other possible effects on the host (eg,
      immunogenicity), and the niche that each occupies in the armamentarium for
      hemophilia therapy. The difficulty in applying a cost-efficacy model for making
      societal choices about appropriate product selection is discussed in the context
      of potential or emerging threats to CFC safety (e.g., variant Creutzfeldt-Jakob
      disease).

PMID- 11441417
TI  - The Food and Drug Administration's perspective on plasma safety.
AB  - The balance between acceptable plasma-product safety and the demand for those
      products involves a finite (but very low) level of risk for transmitting
      infectious diseases. The Food and Drug Administration (FDA) has focused on the
      use of a triple safety net to provide safe plasma products. This safety net
      includes donor selection, plasma testing, and inventory hold (look back and
      retrieval). Although each part of this safety net contributes to reducing the
      overall viral load in plasma products, each part may not contribute equally to a
      safe product in all cases. Donor selection is not universally reliable, and
      plasma antibody testing can be negative for a disease during its seroconversion
      window period. However, inventory hold (especially for first-time donors) has
      added to the usefulness of the other safety-net components. This review article
      provides a brief overview of each safety component and subsequent related
      improvements, including advances in antibody testing for donor screening and the
      addition of PCR testing for donor minipools and viral inactivation procedures
      during plasma-product manufacturing. Dilemmas created by this safety approach are
      also discussed, including the debate over zero risk of product versus cost and
      the impact on donors when they test positive for the various diagnostic tests
      used. Other dilemmas include the decision to include or exclude currently used
      plasma tests with the advent of polymerase chain reaction (PCR) testing, expanded
      use of PCR to test for other plasma-transmitted diseases that impart limited risk
      to recipients, and the role of antigen/antibody interactions in plasma products,
      especially as the latter relate to plasma-pool and final-product testing.

PMID- 11441418
TI  - Viral reduction techniques: types and purpose.
AB  - Viral reduction techniques help assure the highest level of plasma-product safety
      that is possible using today's technology. However, worldwide travel and changing
      demographics could bring new pathogens into focus and thus require plasma-product
      manufacturers to be continually vigilant in their efforts to refine current
      reduction techniques and develop and apply new methods. This review focuses on
      all the currently used viral reduction techniques, why viral reduction continues
      to be important (even with the use of polymerase chain reaction techniques to
      improve plasma screening), and possible future directions for viral reduction.
      When exploring current approaches, including heat treatment (especially
      pasteurization), solvent/detergent, pH changes, and ultrafiltration, this review
      also includes (where applicable) the negative impact of these techniques on
      product integrity and/or viruses not destroyed. Other techniques (eg,
      chromatography) and the fractionation steps relevant in the production of
      selected plasma products may also impart viral reduction and are briefly
      assessed. Relying on an extensive review of current online and printed
      literature, this article also discusses the current US and European guidelines
      and regulations that impact viral reduction techniques. This information includes
      emphasis on the recommendation to use at least 2 reduction techniques (each with
      a different mode of action) for each plasma product so as to substantially reduce
      both enveloped and nonenveloped viruses. The approach to validation studies and
      results from specific studies are reviewed, and future approaches for viral
      reduction are described.

PMID- 11441419
TI  - One manufacturer's approach to using nucleic acid testing for enhanced plasma
      product safety.
AB  - Source plasma must contain the lowest possible pathogen bioburden so as to
      minimize the stress placed on subsequent viral reduction steps. Differences exist
      between European and US criteria for developing assays used to detect these viral
      pathogens. The approach used by 1 plasma-product manufacturer is described here.
      By adding polymerase chain reaction (PCR) detection techniques for various viral
      pathogens (including human immunodeficiency virus-1, hepatitis C virus, and
      hepatitis B virus) to the plasma screening process, this manufacturer maximizes
      the use of cutting-edge technology for plasma product safety while satisfying
      both European and US criteria and requirements for this process. The protocol
      begins with maxipool testing and eventually identifies any specific donor plasma
      that might be positive in the contributing minipools. The goal is to identify
      reactive donors for possible periodic monitoring and to use only nonreactive
      donations to continue producing a particular plasma product. Controversy
      surrounding the use of PCR to screen emerging organisms of questionable
      pathogenicity or known organisms that are of minimal pathogenicity for most of
      the population is also discussed, and possible solutions to this debate are
      provided.

PMID- 11441420
TI  - The impact of Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease on
      plasma safety.
AB  - Although the true risk of transmitting (classical) Creutzfeld-Jakob Disease (CJD)
      and variant CJD (vCJD) via transfusion is likely very minimal, a review of prions
      and the impact of these associated prion diseases is timely because of their
      current effect on safety policies in the blood-plasma industry. Various types of
      human and animal prion diseases are outlined and reviewed, with emphasis on the
      importance of cross-species transmission as is relevant for vCJD. Review of the
      prion theory focuses on the relationship of prions to disease pathophysiology,
      prion resistance to protein modification, and potential prion transmission.
      Causes (with emphasis on iatrogenic CJD) and diagnosis of clinical CJD are
      described and contrasted with the same for vCJD. The origin of vCJD, the
      pathophysiologic questions surrounding this condition, and the latest diagnostic
      tests and research are also reviewed. Comparison of transmission feasibility
      versus actual transmission of CJD or vCJD by blood or blood products is then
      explored. Reasons for the discrepancy between theoretic and actual transmission
      for CJD and the body of evidence provided by look-back studies are examined. When
      compared with CJD, reasons are provided for the higher theoretic risk of
      transmitting vCJD by blood products. Studies evaluating transmission by blood
      products in animals are considered. Transfusion practices that include European
      and US criteria to prevent vCJD through blood products are reviewed. This
      includes the debate surrounding product leukoreduction, deferral of donors at
      high risk either for exposure to vCJD or for contracting CJD, targeted
      elimination of donor plasma, and how some policies may have contributed to
      product shortages.

PMID- 11441421
TI  - Going from the bedside back to the bench with ecopipam: a new strategy for
      cocaine pharmacotherapy development.

PMID- 11441422
TI  - Effects of ecopipam, a selective dopamine D1 antagonist, on smoked cocaine self
      administration by humans.
AB  - RATIONALE: Data obtained in laboratory animals and humans suggest that dopamine
      D1 receptor antagonists decrease cocaine self-administration and block cocaine's
      discriminative stimulus and subjective effects. OBJECTIVES: This study
      investigates the effects of the selective dopamine D1 antagonist, ecopipam (SCH
      39166), on the reinforcing, cardiovascular, and subjective effects of cocaine in
      humans. METHODS: Ten non-treatment-seeking cocaine smokers (two females, eight
      males), residing on an inpatient research unit, were maintained on placebo and
      ecopipam (100 mg p.o.) in random order using a within-subjects, cross-over
      design. Cocaine self-administration (0, 12, 25, and 50 mg) was tested beginning
      on the 5th day of each 8-day maintenance condition. A six-trial choice procedure
      (cocaine vs $5 merchandise vouchers) was utilized, with sessions consisting of
      one sample trial, when participants smoked the cocaine dose available that day,
      and five choice trials, when participants chose between smoking the available
      cocaine dose or receiving one merchandise voucher. RESULTS: In the presence of
      placebo cocaine, ecopipam significantly decreased cocaine craving while
      increasing alcohol and tobacco craving. In the presence of active cocaine,
      ecopipam increased cocaine self-administration (12 mg) and increased ratings of
      "good drug effect," "high," "stimulated," and dose quality (25 and 50 mg).
      Ecopipam produced small but significant increases in blood pressure, regardless
      of cocaine dose. CONCLUSIONS: Maintenance on the long-acting dopamine D1
      antagonist, ecopipam, enhanced both cocaine self-administration as well as its
      subjective effects compared to maintenance on placebo. These data suggest that
      chronic antagonism of the dopamine D1 receptor may not be a useful approach for
      the treatment of cocaine abuse.

PMID- 11441423
TI  - Repeated administration of the D1/5 antagonist ecopipam fails to attenuate the
      subjective effects of cocaine.
AB  - RATIONALE: Dopaminergic compounds have been targeted as potential treatments for
      cocaine abuse because of the known role of dopamine systems in drug
      reinforcement. Recent preclinical and human data have focused on the D1/5
      antagonist, SCH 39166 (ecopipam), as a potential therapeutic agent. OBJECTIVES:
      The objective of the present study was to determine whether treatment with
      chronic ecopipam can blunt or block the subjective effects of cocaine in the
      absence of significant behavioral impairment or toxic physiological effects.
      METHODS: Four doses of ecopipam (0, 10, 25, and 100 mg p.o.) were administered
      daily for 1 week each in double-blind, random order to inpatient cocaine
      dependent volunteers (n = 10). Cocaine challenge doses (0, 25, and 50 mg/70 kg
      i.v.) were administered on the 7th day in ascending order, 1 h apart. RESULTS:
      Ecopipam alone produced reliable dose-dependent deficits in performance on the
      digit symbol substitution task (DSST) and the circular lights task, but not a
      balance task. Impairment on the DSST waned with repeated dosing suggesting the
      development of tolerance. Ecopipam resulted in few direct subjective effects.
      Cocaine alone produced dose-dependent changes in prototypic subjective and
      physiological measures, however, ecopipam largely failed to alter either
      cocaine's direct effects or the desire for cocaine. CONCLUSIONS: Although the
      performance effects verify that these doses of ecopipam were behaviorally active,
      the absence of an attenuation of cocaine's effects of craving for cocaine in this
      chronic dosing paradigm suggests this compound is unlikely to be an effective
      pharmacotherapy for cocaine abuse.

PMID- 11441424
TI  - Behavioral and neurochemical consequences of repeated nicotine treatment in the
      serotonin-depleted rat.
AB  - RATIONALE: Repeated exposure to addictive drugs causes neuroadaptive alterations
      that are proposed to increase the incentive motivation to consume drugs and to
      decrease the ability to inhibit such inappropriate motivational impulses and
      responses. Together, these behavioral consequences of drug intake may underlie
      the compulsive drug-seeking and -taking behaviors observed in drug abuse.
      OBJECTIVE: Brain serotonin (5-HT) has been implicated in these mechanisms and
      this study therefore investigated the consequences of brain 5-HT depletion on the
      behavioral and neurochemical effects induced by repeated daily nicotine treatment
      (15 days) in male rats. METHODS: The effects of the present pharmacological
      manipulations were evaluated behaviorally (locomotor activity, the elevated plus
      maze) and neurochemically (microdialysis, brain biochemistry). RESULTS: Depletion
      of brain 5-HT produced behavioral disinhibition in the elevated plus-maze. In 5
      HT-depleted animals, nicotine-induced locomotor sensitization was observed on
      treatment days 5, 10, and 15, but only on day 15 in the sham-operated rats.
      Postsensitization, the locomotor stimulatory effects of amphetamine and the
      dopamine receptor agonists SKF 38,393, apomorphine, and quinpirole were decreased
      in 5-HT-depleted animals, an effect that appeared to be more pronounced in
      nicotine-treated rats. Repeated nicotine treatment sensitized the nicotine
      induced elevation of the extracellular accumbal dopamine levels in sham-operated,
      but not in 5-HT-depleted rats, and was also associated with decreased D2
      autoreceptor function in both nicotine-treated experimental groups. CONCLUSIONS:
      Depletion of brain 5-HT, which produces behavioral disinhibition, may slightly
      facilitate the overall expression of locomotor sensitization to nicotine and
      differentially affect the pre- and postsynaptic neuroadaptive events involved in
      the expression of these phenomena.

PMID- 11441425
TI  - Subjective, psychomotor, and physiological effects of cumulative doses of mixed
      action opioids in healthy volunteers.
AB  - RATIONALE: Conducting complete dose-response evaluations of multiple drugs in a
      single within-subjects experiment is very time-consuming when a complete session
      is required for evaluation of each dose. OBJECTIVE: To evaluate a within-session
      cumulative-dosing procedure as a potentially efficient method for conducting dose
      response evaluations of mixed-action opioids. METHODS: Fifteen healthy volunteers
      received intravenous injections of saline, butorphanol, nalbuphine, pentazocine,
      or morphine in a randomized, double-blind, crossover design. Subjects received
      one injection per hour for the first 4 h, and a 3-h recovery period followed.
      Saline was injected first, then saline or increasing doses of each drug (except
      pentazocine, see below) were administered every hour for the next 3 h. The
      absolute doses per injection were morphine and nalbuphine 2.5, 5, and 10 mg/70
      kg, butorphanol 0.5, 1, and 2 mg/70 kg, and pentazocine 7.5, 15, and 0 mg/70 kg.
      (The highest dose of pentazocine was omitted because of the risk of dysphoria and
      psychotomimesis). These injections resulted in cumulative doses of morphine or
      nalbuphine 2.5, 7.5, and 17.5 mg/70 kg, butorphanol 0.5, 1.5, and 3.5 mg/70 kg,
      and pentazocine 7.5 and 22.5 mg/70 kg. Mood, psychomotor performance, and vital
      signs were assessed. RESULTS: Effects of all opioids were similar, with some
      exceptions. Butorphanol had the strongest effects on psychomotor performance and
      some subjective effects. Morphine was associated with delayed or prolonged side
      effects. CONCLUSIONS: Orderly dose-response functions and replication of results
      of single-dosing studies confirmed that the cumulative-dosing procedure is an
      efficient way of determining dose-response functions for multiple opioids within
      the same subjects.

PMID- 11441426
TI  - Cigarette smoking and attention: processing speed or specific effects?
AB  - RATIONALE: It has been evidenced that nicotine acts on some dimensions of human
      attention. OBJECTIVE: This study was carried out to test whether the positive
      effects of nicotine usually observed on the posterior system are specific or
      should rather be explained in terms of an effect of nicotine on eye movement
      velocity. METHODS: Ten participants were submitted to four tasks assessing
      attention. The tasks were borrowed from Zimmermann and Fimm's Battery for the
      Assessment of Attention: alert, eye movements, visual search and incompatibility.
      The order of the different tasks was balanced among participants. A within
      subjects repeated-measure design was used. Participants received a 0.9-mg or 0.1
      mg nicotine cigarette. The 0.1-mg cigarette was used as control. The order of
      administration of doses over sessions was counterbalanced. During the testing
      day, volunteers smoked their own cigarette and then waited 3 h without smoking.
      At the end of this abstinence period, participants completed the baseline tests
      before smoking an experimental cigarette ad libitum. They were then tested again.
      RESULTS: Participants who received nicotine appeared to respond faster in an eye
      movement task--a task associated with a non-elaborated attentional process.
      Similarly, their alert state improved. On the contrary, no effect of nicotine was
      observed in the incompatibility task and in the visual search task depending on
      elaborated attentional process. CONCLUSIONS: Data support previous observations
      and suggest that, first, non-elaborated information processing appeared to be
      more sensitive to nicotine and, second, this effect is not due to a velocity
      factor.

PMID- 11441427
TI  - The alpha 2 adrenoceptor antagonists RX 821002 and yohimbine delay-dependently
      impair choice accuracy in a delayed non-matching-to-position task in rats.
AB  - RATIONALE: alpha 2 adrenoceptor mechanisms appear to play a role in the
      performance of delayed response working memory tasks but there are contradictory
      results. OBJECTIVE: To investigate whether RX 821002 (2-methoxy-idazoxan) and
      yohimbine and would affect the performance of the delayed non-matching-to
      position (DNMTP) task in rats and compare the effects to those of the cholinergic
      antagonist scopolamine. METHODS: Male Lister Hooded rats trained to criterion in
      an operant DNMTP task (0-48 s delay intervals) were administered vehicle, RX
      821002 (0.3, 1, 3 mg/kg s.c.), yohimbine (1, 3 mg/kg. s.c.) or scopolamine (0.05
      mg/kg, s.c.). Together with choice accuracy, the motor performance of the task
      was measured. RESULTS: It was found that: (1) both RX 821002 and yohimbine
      statistically significantly reduced choice accuracy dose- and delay-dependently
      and in a similar magnitude to that of scopolamine while modifying the motor
      aspects of task performance delay-independently and (2) RX 821002 produced mainly
      rate-decreasing effects. Yohimbine exerted stimulatory effects at the lowest dose
      and rate-decreasing effects at the highest dose, a profile consistent with that
      already described in operant tasks. CONCLUSION: The results confirm that alpha 2
      antagonists delay-dependently impair choice accuracy in a delayed-response
      paradigm.

PMID- 11441428
TI  - Three-choice discrimination in pigeons is based on relative efficacy differences
      among opioids.
AB  - RATIONALE: Drug discrimination assays can provide important information on
      receptor selectivity and relative efficacy to guide the classification and
      characterization of opioid agonists. OBJECTIVES: A three-choice discrimination
      was established among high efficacy opioid agonist morphine, low efficacy opioid
      agonist nalbuphine, and saline to examine the conditions under which differences
      in relative efficacy might serve as a basis for stimulus control. METHODS: Seven
      White Carneau pigeons were trained to discriminate among 5.6 mg/kg nalbuphine,
      3.2 mg/kg morphine, and saline under fixed ratio 30 (FR30) schedules of food
      reinforcement. Substitution and antagonism experiments were then conducted with
      mu, kappa, and delta opioids and naltrexone, respectively and the percent
      responding appropriate to the training stimuli was determined. RESULTS: Low,
      intermediate, and high doses of morphine produced > or = 80% saline-, > or = 60%
      nalbuphine-, and > or = 96% morphine-appropriate responding, respectively. Low
      and high doses of nalbuphine produced > or = 80% saline- and nalbuphine
      appropriate responding, respectively. In substitution tests, low doses of
      fentanyl and etorphine produced partial nalbuphine-appropriate responding (20
      60%) and high doses produced > or = 60-80% morphine-appropriate responding.
      Intermediate doses of buprenorphine and dezocine produced > or = 60-80%
      nalbuphine-appropriate responding and high doses produced > or = 80% morphine
      appropriate responding. The lower efficacy agonists butorphanol, nalorphine, and
      levallorphan produced > or = 40-80% nalbuphine-appropriate responding. The kappa
      agonists spiradoline and U50,488 produced approximately > or = 50% nalbuphine
      appropriate responding whereas d-amphetamine, saline, and delta agonists BW373U86
      and SNC 80 produced > or = 80% saline-appropriate responding. Naltrexone produced
      > or = 80% saline-appropriate responding and reversed the stimulus effects of
      morphine and nalbuphine. CONCLUSIONS: The discrimination between morphine and
      nalbuphine in pigeons is predominantly based on the relative efficacy differences
      between morphine, a higher-efficacy mu agonist and nalbuphine, a lower-efficacy
      mu agonist.

PMID- 11441429
TI  - Effects of repeated oral methamphetamine administration in humans.
AB  - RATIONALE: Although methamphetamine use has increased over the past several
      years, few studies have evaluated the effects of repeated methamphetamine
      administration in humans. OBJECTIVES: Because methamphetamine is often taken in a
      pattern of repeated use followed by a period of abstinence, the present study
      sought to evaluate the effects of repeated methamphetamine administration in
      humans. The hypothesis was that tolerance would develop to methamphetamine's
      effects. METHODS: Seven normal, healthy volunteers participated in a 15-day
      residential study. Participants completed subjective-effects questionnaires and
      psychomotor performance tasks repeatedly throughout the experimental day. Oral
      methamphetamine (5, 10 mg BID) was administered on days 4-6 and 10-12; placebo
      was administered on all other study days. RESULTS: Relative to placebo baseline,
      only two "positive" subjective ratings ("I feel a good drug effect" and "I feel
      high") were significantly elevated, and only on the 1st day of methamphetamine
      administration. In contrast, numerous "negative" ratings, including "I feel..."
      "a bad drug effect," "dizzy," and "flu-like symptoms" were elevated on the 3rd
      day of methamphetamine administration. Total caloric intake decreased and sleep
      was disrupted after methamphetamine administration, relative to baseline.
      CONCLUSIONS: The pattern of methamphetamine's positive subjective effects were
      altered with chronic administration such that tolerance, or a decreased effect,
      occurred after repeated administration. In contrast, methamphetamine's negative
      subjective effects increased over days. These results suggest that in this
      population of normal volunteers, the abuse liability of oral methamphetamine is
      relatively low.

PMID- 11441430
TI  - Chronic ethanol exposure results in increased acute functional tolerance in
      selected lines of HAFT and LAFT mice.
AB  - RATIONALE AND OBJECTIVES: Functional (pharmacodynamic) ethanol tolerance can be
      evidenced within a single session of exposure to ethanol (acute or within-session
      tolerance), or after repeated ethanol exposures (chronic or between-session
      tolerance). To investigate whether acute and chronic tolerance to ethanol are
      inter-related phenomena, the effect of chronic ethanol exposure was evaluated in
      mice selectively bred for high (HAFT) or low (LAFT) acute functional tolerance to
      an ataxic effect of ethanol, i.e., loss of balance on a stationary dowel.
      METHODS: Mice were tested for sensitivity (threshold ethanol concentration for
      loss of balance on the stationary dowel) and acute functional tolerance to
      ethanol before and after a regimen of chronic ethanol exposure (twice-daily
      ethanol injections for 6 days). RESULTS: Chronic ethanol treatment did not alter
      the threshold for ethanol's ataxic effect (i.e., produced no change in
      sensitivity). However, this treatment, in a dose-dependent manner, resulted in an
      increase in the magnitude and rate of development of acute functional tolerance.
      CONCLUSIONS: This finding supports previous postulates that chronic ethanol
      tolerance can be characterized by a more rapid acquisition or a greater magnitude
      of acute (within-session) tolerance. However, the increase in acute tolerance
      that occurred after chronic ethanol exposure was similar in both selected lines
      of mice, indicating little or no genetic correlation between acute tolerance and
      chronic tolerance.

PMID- 11441431
TI  - A neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) to rats
      results in a long-term defect in thermoregulation.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") administration to
      rats produces damage to cerebral 5-HT nerve endings; however, the long-term
      functional consequences of this damage are poorly understood. OBJECTIVE: To
      confirm that MDMA administration produces a long-term effect on thermoregulation
      and investigate the mechanisms involved. METHODS: Male Dark Agouti rats were
      injected with a neurotoxic dose of MDMA (12.5 mg/kg i.p.). Five to 6 weeks later,
      they were exposed to high ambient temp (30 degrees C) for 60 min followed by a
      return to normal temp (20 degrees C), with rectal temperature being measured
      under both conditions. Further groups of MDMA-pretreated rats were challenged
      with 8-OH-DPAT and their temperature response measured. RESULTS: MDMA
      administration produced acute hyperthermia. Rectal temperature had normalised 24
      h later and was similar to saline-injected controls over the following 15 days.
      MDMA administration produced a 37% loss in hypothalamic 5-HT content 18 days
      later. When MDMA-pretreated rats were subjected to high ambient temperature 33
      days posttreatment, they displayed both a faster rise in rectal temperature and
      sustained hyperthermia when returned to normal conditions. There was no
      difference in their hypothermic response to the 5-HT1A agonist 8-OH-DPAT.
      CONCLUSIONS: A neurotoxic dose of MDMA resulted in impaired thermoregulation when
      rats were exposed to high ambient temperature. 5-HT1A receptor mechanisms were
      unaltered. Impaired serotonergic function following MDMA presumably alters the
      neurotransmitter balance, thereby compromising thermoregulation. Heavy
      recreational users of MDMA may also have impaired thermoregulation and thus be at
      greater risk of an acute adverse response to MDMA in a hot crowded dance
      environment.

PMID- 11441432
TI  - Location preference related to smoked heroin self-administration by rhesus
      monkeys.
AB  - RATIONALE: Although common in humans, little is known about the reinforcing
      efficacy of smoked heroin in laboratory animals. OBJECTIVES: To evaluate the
      reinforcing efficacy of smoked heroin in non-opioid dependent, non-human
      primates. METHODS: Self-administration and location-preference measures were
      obtained by having monkeys live in two chambers with heroin self-administration
      (0, 0.3, 0.6 mg/kg; eight dosings available per day) specific to one chamber and
      no commodity available in the other chamber. Operant responding reinforced by
      smoked heroin provided a self-administration measure of reinforcement, and the
      length of time monkeys spent in the heroin-associated chamber provided a location
      preference estimate of reinforcing efficacy. RESULTS: Four of six monkeys
      acquired heroin self-administration: these monkeys completed six to eight smoking
      trials each day when either of the active heroin doses was available. Urine
      toxicology confirmed that monkeys were absorbing the smoked heroin. The number of
      completed smoking trials rapidly decreased under extinction conditions,
      indicating that smoked heroin was an efficacious reinforcer using the self
      administration measure. Monkeys developed a location preference for the chamber
      where heroin was self-administered, indicating that smoked heroin was an
      efficacious reinforcer using the location-preference measure. CONCLUSIONS: Smoked
      heroin is an efficacious reinforcer in non-opioid dependent rhesus monkeys as
      measured using a self-administration procedure and estimated using a location
      preference procedure.

PMID- 11441433
TI  - Central effects of urotensin-II following ICV administration in rats.
AB  - RATIONALE: Urotensin-II (U-II) has recently been identified as an agonist for the
      G-protein-coupled receptor, GPR14. Detection of both U-II and GPR14 mRNA in the
      brain and spinal cord is consistent with a role for U-II in the CNS. However, the
      effects of central administration of U-II in rodents have not been reported
      previously. OBJECTIVES: To determine the localisation of GPR14 mRNA in rat
      tissues and to investigate the behavioural and endocrine effects of human U-II
      (hU-II) following intracerebroventricular (ICV) administration in rats. METHODS:
      Experiments were carried out in male Sprague-Dawley rats. Expression of GPR14
      mRNA in rat brain was determined by semi-quantitative RT-PCR. Effects of hU-II on
      general behaviours were assessed by an observer and the motor activity response
      was measured by an automated activity monitor. Plasma hormones and [DOPAC +
      HVA]/[DA] and [5-HIAA]/[5-HT] ratios in five brain areas were measured 20 min
      post-hU-II (ICV). RESULTS: GPR14 mRNA expression was found in whole brain tissue
      and in all CNS regions tested. GPR14 mRNA expression was also detected in the
      periphery; highest levels were found in the heart. Following ICV administration,
      hU-II (3-10 micrograms ICV) increased rearing and grooming, and increased motor
      activity in a familiar environment. Further, hU-II increased plasma prolactin and
      TSH but did not affect levels of corticosterone. hU-II had no effects on dopamine
      or 5-HT levels or their metabolites in the frontal cortex, hippocampus,
      hypothalamus, striatum and nucleus accumbens. CONCLUSIONS: These data provide
      further insight into the distribution of GPR14 mRNA within the CNS and show for
      the first time that hU-II causes marked behavioural and endocrine effects.

PMID- 11441434
TI  - Association between depressive behavior and absence of serotonin-dopamine
      interaction in the nucleus accumbens.
AB  - RATIONALE: Current hypotheses on the etiology of depression attribute the
      disorder to alterations in serotonin and norepinephrine neurotransmission.
      However, the relationship between these alterations and depressive behavior is
      poorly understood. Conversely, an interaction between the serotonergic and
      dopaminergic systems in the nucleus accumbens has been established. Since
      motivation and hedonia have been associated with dopamine release in the nucleus
      accumbens, we decided to test its modulation by serotonin in relation to
      depressive-like behavior. OBJECTIVES AND METHODS: The extracellular dopamine
      levels in the nucleus accumbens were studied in vivo in Flinders Sensitive Line
      (FSL, a rat model of depressive behavior) and control rats, before and after
      antidepressant treatment. Rats were chronically treated with the antidepressants
      desipramine (5 mg/kg/day) and paroxetine (7.5 mg/kg/day) for 18 consecutive days.
      As a measure of depressive behavior we used a modified swim test. The release of
      dopamine in response to local serotonin application was monitored using the
      microdialysis technique. RESULTS: Serotonin (0.5 microM) facilitated dopamine
      release in the nucleus accumbens of control rats. In FSL rats, basal
      extracellular dopamine levels in the nucleus accumbens were 40% lower than in
      control rats and did not increase in response to serotonin stimulation. However,
      chronic antidepressant treatment of the FSL rats normalized the serotonin
      dopamine interaction as well as their behavioral deficiencies. CONCLUSIONS: The
      inability of serotonin to stimulate dopamine release in the nucleus accumbens,
      thereby leading to anhedonia and lack of motivation, may therefore be an
      essential factor in the onset of depression and a target for modulation by
      antidepressant drugs.

PMID- 11441435
TI  - Cholinergic modulation of speed of early information processing: the effect of
      donepezil on inspection time.
AB  - RATIONALE: Selective cholinergic receptor agonists and antagonists have been
      shown to modulate inspection time, a measure of speed of early information
      processing. OBJECTIVE: The present study aimed to examine the effects of globally
      increasing cholinergic function with the acetylcholinesterase inhibitor donepezil
      on inspection time. METHODS: Fourteen healthy subjects participated in a
      randomised double-blind, placebo controlled trial in which all subjects were
      tested under either acute placebo or donepezil (5 mg) treatment conditions.
      Testing was conducted pre- and 90 min post-drug administration. RESULTS: There
      was a significant decrease in inspection time in the donepezil condition compared
      to the placebo condition (F = 12.86; P < 0.01). DISCUSSION: The decrease or
      improvement of inspection time following donepezil administration is consistent
      with the role of the cholinergic system in modulating speed of information
      processing, and adds evidence that inspection time may serve as a physiological
      index of the integrity of the cholinergic system.

PMID- 11441436
TI  - High light intensity: a critical factor in the wind-tunnel flight of two scarabs,
      the rose chafer and Japanese beetle.
AB  - We analyzed the flight of the rose chafer Macrodactylus subspinosus (F.)
      (Melolonthinae: Scarabaeidae) and the Japanese beetle Popillia japonica Newman
      (Rutelinae: Scarabaeidae) in a wind tunnel with controlled humidity, temperature,
      light, and airflow. The data indicate that an optimum combination of light and
      temperature dramatically improves their response to lures. Both species took off
      upwind, oriented to, and contacted the odor source well (40-60%) when light
      intensity was > 50% of a clear day, temperature was 26-27 degrees C, and relative
      humidity was 65-75%.

PMID- 11441437
TI  - Does pheromone biology of Lambdina athasaria and L. pellucidaria contribute to
      their reproductive isolation?
AB  - Recently, 7-methylheptadecane and 7,11-dimethylheptadecane have been reported as
      sex pheromone components of both spring hemlock looper (SHL), Lambdina athasaria,
      and pitch pine looper (PPL), Lambdina pellucidaria. Our objective was to test the
      hypothesis that SHL and PPL are reproductively isolated, in part, through species
      specificity in: (1) absolute configuration of pheromone components, (2) diel
      periodicity of pheromonal communication, and/or (3) seasonal flight period. In
      coupled gas chromatographic-electroantennographic detection (GC-EAD) analyses of
      stereoselectively synthesized (7S)- and (7R)-7-methylheptadecane [7S; 7R] as well
      as (7S,11S)-, (7R,11R)-, and (meso-7,11)-7,11-dimethylheptadecane [7S,11S;
      7R,11R; meso-7,11], only 7S and meso-7,11 elicited responses by male SHL and PPL
      antennae. In field experiments, male SHL and PPL were attracted only to lures
      containing 7S plus meso-7,11. In hourly recordings of trap-captured males, SHL
      and PPL in their respective habitats were trapped between 24:00 and 03:00 hr.
      Capture of both SHL and PPL in pheromone-baited traps throughout June indicated
      overlapping seasonal flight periods. These findings of identical absolute
      configuration of pheromoal components, diel periodicity of pheromonal
      communication, and overlap of seasonal flight periods support synonymy of SHL and
      PPL. Finite taxonomic classification of PPL and SHL must await careful assessment
      of further criteria, such as morphometrics, molecular comparisons and ecological
      analyses.

PMID- 11441438
TI  - Putative steroidal pheromones in the round goby, Neogobius melanostomus:
      olfactory and behavioral responses.
AB  - To identify potential hormonal pheromones of the round goby (Neogobius
      melanostomus), a species recently introduced to the Great Lakes, we used electro
      olfactogram (EOG) recording to examine olfactory responsiveness to more than 100
      steroids and prostaglandins. Neogobius detected free and conjugated 18-, 19- and
      21-carbon steroids, but did not detect prostaglandins. EOG cross-adaptation, used
      to determine if Neogobius can discriminate the detected compounds at the sensory
      level, suggested that the detected steroids act on four classes of olfactory
      receptor mechanisms named (according to the most potent ligand for each):
      estrone, 17 beta-estradiol-3 beta-glucuronide, etiocholanolone, and
      dehydroepiandrosterone-3-sulfate. Although none of the detected steroids induced
      reproductive behaviors, exposure to steroids from three of the four receptor
      classes (estrone, 17 beta-estradiol-3 beta-glucuronide, or etiocholanolone)
      increased ventilation rate in males, whereas only etiocholanolone increased
      ventilation rate in females. Using the ventilation increase as a behavioral
      bioassay of steroid detection, behavioral cross-adaptation studies in males
      demonstrated that steroids discriminated at the sensory level are also
      discriminated behaviorally. These findings suggest the round goby may use
      steroids as putative pheromones.

PMID- 11441439
TI  - 1-octen-3-ol isolated from bont ticks attracts Amblyomma variegatum.
AB  - Volatiles from various life-stages of the bont ticks Amblyomma variegatum and A.
      hebraeum were collected by using solid-phase microfibers and charcoal traps. An
      octenol isomer was found to be a major constituent of most of the tick material
      sampled and was identified as 1-octen-3-ol by gas chromatography-mass
      spectrometry and by using antenna of the tsetse fly Glossina brevipalpis in gas
      chromatography-linked antennogram detection. Release of this compound increased
      during molt to adulthood and following mechanical disturbance of adult ticks. (R)
      (-)-1-Octen-3-ol and racemate 1-octen-3-ol both induce an increase in upwind walk
      to the odor source from A. variegatum in an airstream on a servosphere. Volatiles
      from tick exuviae plus feces and from dead ticks also attracted A. variegatum,
      suggesting that 1-octen-3-ol may contribute to the aggregation response of
      Amblyomma spp. on such substrates. 2,6-Dichloroanisol and 2,5-dimethylpyrazine
      also were detected in volatiles from the ticks but induced no behavioral
      responses on the servosphere. The suspected tick pheromone component, 2,6
      dichlorophenol, was detected from A. variegatum adults cut into pieces but had no
      effect on the behavior of A. variegatum on the servosphere at a range of doses.

PMID- 11441440
TI  - Preparative chiral liquid chromatography for enantiomeric separation of
      pheromones.
AB  - Cellulose triacetate was investigated as a chiral stationary phase for
      preparatively separating the enantiomers of lineatin, frontalin, exo-brevicomin,
      endo-brevicomin, verbenone, (E)-conophthorin, and grandisol. Tens of milligrams
      of both enantiomers were efficiently prepared in high percentage enantiomeric
      excess from one injection of each compound except grandisol. We prepared
      grandisyl acetate, benzoate, and 4-bromobenzoate to determine if derivatization
      of the free alcohol might improve separation. Of these, grandisyl 4-bromobenzoate
      provided the best separation but was still not very well resolved. Preparative
      separation of enantiomers on cellulose triacetate is a viable alternative to
      stereoselective synthesis when semiochemicals of very high enantiomeric purity
      are required for biological testing.

PMID- 11441441
TI  - Analysis of volatiles induced by oviposition of elm leaf beetle Xanthogaleruca
      luteola on Ulmus minor.
AB  - Egg deposition of the elm leaf beetle Xanthogaleruca luteola causes the emission
      of volatiles from its food plant, Ulmus minor. These volatiles are exploited by
      the egg parasitoid, Oomyzus gallerucae, to locate its host. In contrast to other
      tritrophic systems, the release of volatiles is not induced by feeding but by egg
      deposition. Previous investigations showed that the release is systemic and can
      be triggered by jasmonic acid. Comparison of headspace analysis revealed
      similarities in the blend of volatiles emitted following egg deposition and
      feeding. The mixture consists of more than 40 compounds; most of the substances
      are terpenoids. Leaves next to those carrying eggs emit fewer compounds. When
      treated with jasmonic acid, leaves emit a blend that consists almost exclusively
      of terpenoids. Dichloromethane extracts of leaves treated with jasmonic acid were
      also investigated. After separation of extracts of jasmonate induced elm leaves
      on silica, we obtained a fraction of terpenoid hydrocarbons that was attractive
      to the parasitoids. This indicates that jasmonic acid stimulates the production
      of terpenoid hydrocarbons that convey information of egg deposition to the
      parasitoid.

PMID- 11441442
TI  - Ecologically active 2-octanoylcyclohexane-1,3-dione from Philodendron guttiferum.
AB  - The novel naturally occurring 2-octanoylcyclohexane-1,3-dione 1 was isolated in
      its enol form from P. guttiferum (Araceae). Its chemical ecological relevance is
      discussed. There was mass spectral evidence for the presence of small amounts of
      the homologous 2-decanoyl and 2-dodecanoyl derivatives.

PMID- 11441443
TI  - Nootkatone is a repellent for Formosan subterranean termite (Coptotermes
      formosanus).
AB  - We examined the behavior of Formosan subterranean termites toward one of the
      components of vetiver grass oil, the roots of which manufacture insect
      repellents. We found nootkatone, a sesquiterpene ketone, isolated from vetiver
      oil is a strong repellent and toxicant to Formosan subterranean termites. The
      lowest effective concentration tested was 10 micrograms/g substrate. This is the
      first report of nootkatone being a repellent to insects.

PMID- 11441444
TI  - Chemosensory assessment of predation risk by slimy sculpins (Cottus cognatus):
      responses to alarm, disturbance, and predator cues.
AB  - Slimy sculpins (Cottus cognatus) are small benthic fish that commonly co-occur
      with predatory fishes throughout most of their range in North America. In two
      laboratory experiments we examined the nature and extent of responses of slimy
      sculpins to chemosensory cues from predatory brook trout (Salvelinus fontinalis)
      and chemical alarm cues released by conspecific sculpins. Sculpins responded to
      three different classes of chemical stimuli: (1) cues of predatory brook trout,
      (2) damage-released alarm cues from conspecific sculpins, and (3) disturbance
      cues from conspecific sculpins. Sculpins did not distinguish between trout fed
      different diets; however, the presence of damage-released alarm cues did enhance
      the intensity of response to the predator chemicals. A histological analysis of
      the skin of sculpins revealed the presence of large sacciform cells that may act
      as the source of chemical alarm signals.

PMID- 11441445
TI  - Ontogeny constrains systemic protease inhibitor response in Nicotiana attenuata.
AB  - Protease inhibitors (PIs) are plant compounds that can inhibit proteases of
      mammal, insect, or pathogen origin and are frequently induced by mechanical
      wounding, insect feeding, or pathogen infection. Nicotiana attenuata is a species
      that induces nicotine, volatiles, and phenolics in response to damage. Here we
      examine the distribution of PIs in N. attenuata to determine if they are part of
      the induced response in this species and if this response is ontogenetically
      constrained. We found that N. attenuata shoot extracts inhibited trypsin (Tryp)
      and chymotrypsin (Chym) activities, while root extracts inhibited Tryp, Chym, and
      the bacterial protease subtilisin (Sub). The highest TrypPI levels were found at
      midday in the source-sink transition leaf, while older or younger leaves
      contained lower TrypPI levels and did not show significant diurnal fluctuations.
      Rosette plants, bolting plants, and flowering plants all contained TrypPIs in
      leaves, stems, and flowers, while seed capsules, seeds, and young seedlings did
      not contain any PIs. PIs in N. attenuata rosette plants were induced by Manduca
      sexta larval feeding, methyl jasmonate (MeJA) treatment, wounding, and
      application of M. sexta oral secretion and regurgitant. The response to MeJA
      application was stronger and longer lasting than to mechanical wounding. The
      direction and magnitude of the systemic response to mechanical wounding or larval
      damage depended on the age of the leaf that was damaged and the frequency of
      wounding. The systemic signal for TrypPI induction appears to follow source-sink
      relations in the plant and to be regulated by the octadecanoid pathway.
      Interestingly, by the time plants reach the flowering stage, they had lost the
      ability to increase PI levels after MeJA treatment. We concluded that plant
      ontogeny constrains both constitutive and inducible PI production in N.
      attenuata.

PMID- 11441446
TI  - Defensive role of secretion of ectal mandibular glands of the wasp Polistes
      dominulus.
AB  - Ectal mandibular glands of insects are exocrine glands localized in the anterior
      lateral region of the head, close to the base of the mandibles. In social wasps,
      the gland is composed of secretory cells and a reservoir into which the secretion
      accumulates. At the time of emission the secretion flows onto a specialized
      cuticular area on the outside of the base of the mandibles. Secretion of Polistes
      dominulus is emitted only when wasps are greatly disturbed or in the presence of
      predators, and its function seems to be mainly defensive. Morphometric studies
      did not reveal any size differences between the glands of the queens and those of
      the workers. GC-MS analyses of the glands identified 32 compounds, mainly acids
      and aldehydes in the range C2-C18. The overall odor, caused by the mixture of
      aldehydes, is distinct. Workers do not respond strongly to the odor. The
      secretion probably serves as a warning signal to vertebrate predators.

PMID- 11441447
TI  - Trade-offs in antiherbivore defenses in Piper cenocladum: ant mutualists versus
      plant secondary metabolites.
AB  - Ant-plant mutualisms may provide indirect evidence for costs of antiherbivore
      defenses when plants demonstrate trade-offs between allocating resources and
      energy into ant attractants versus chemical defenses. We tested the hypothesis
      that ecological trade-offs in defenses are present in Piper cenocladum. This
      plant possesses two distinct defenses: food bodies that attract predatory ants
      that destroy herbivore eggs and amides that deter herbivores. Previous studies
      have demonstrated that the food bodies in P. cenocladum are an effective defense
      because the ants deter herbivory by specialist herbivores. Amides in other Piper
      species have been shown to have toxic qualities, but we tested the additional
      hypothesis that these amides have an actual defensive function in P. cenocladum.
      To test for ecological trade-offs between the two putative defenses, fragments of
      P. cenocladum were examined for the presence of amides both when the plant was
      producing food bodies and when it was not producing food bodies. Plants with
      active ant colonies had redundant defenses, producing food bodies and high levels
      of amides at the same time, but we detected a trade-off in that they had
      significantly lower levels of amides than did plants with no ants. To test for
      the defensive value of P. cenocladum amides, we used an ant bioassay and we
      examined herbivory results from previous experiments with plants that had
      variable levels of amides. These tests demonstrated that amides are deterrent to
      omnivorous ants, leaf cutting ants, and orthopterans. In contrast, the resident
      Pheidole bicornis ants are effective at deterring herbivory by specialist
      herbivores that oviposit eggs on the plant but not at deterring herbivory by
      nonresident omnivores. We concluded that although both amides and food body
      production appear to be costly, redundancy in defenses is necessary to avoid
      damage by a complex suit of herbivores.

PMID- 11441448
TI  - Plant density and nutrient availability constrain constitutive and wound-induced
      expression of trypsin inhibitors in Brassica napus.
AB  - We investigated the effects of plant density on plant size, leaf total soluble
      protein content, and constitutive and wound-induced levels of proteinaceous
      trypsin inhibitors in pot-grown Brassica napus seedlings in two greenhouse
      studies. We manipulated plant density by varying the number of intraspecific
      neighbors surrounding a target plant in the center of each pot. In general,
      constitutive and induced levels of trypsin inhibitors were significantly reduced
      by competition in a density-dependent manner, to the extent that induction was
      greatly reduced or abolished in target plants surrounded by six neighbors. To
      investigate whether the effects of plant density on inhibitor production were
      mediated by nutrient availability, we manipulated the concentration of a complete
      fertilizer applied to target plants surrounded by six neighbors in two greenhouse
      studies. In general, constitutive and wound-induced levels of inhibitors in
      plants surrounded by six neighbors were increased by nutrient addition in a dose
      dependent manner, such that wound-induction was completely restored in competing
      plants under conditions of high nutrient availability. Leaf total soluble protein
      content, measured only in the second trial of each experiment, was not affected
      by any of the treatments. The effects of plant density, nutrient addition, and
      wounding on inhibitor levels in all experiments were independent of their effects
      on above-ground plant size at the time of wounding. Overall, our results suggest
      that decreasing nutrient availability mediates the density-dependent reductions
      in inhibitor levels in B. napus seedings.

PMID- 11441449
TI  - Identification and effects of interaction phytotoxic compounds from exudate of
      Cistus ladanifer leaves.
AB  - Eleven allelochemicals (ferulic acid, cinnamic acid, 4-hydroxybenzoic acid,
      hydroxycinnamic acid, methyl propionate, oxalic acid, methylmalonic acid, p
      anisic acid, butyric acid, 3-hydroxybutyric acid, and azulene) were identified in
      the exudate of Cistus ladanifer L. We studied the effect of each on germination,
      cotyledon emergence, root length, and cotyledon length of Rumex crispus. Three
      groups were distinguished with respect to phytotoxic activity: compounds with low
      activity (ferulic acid, 4-hydroxybenzoic acid, oxalic acid, methylmalonic acid, p
      anisic acid, hydroxybutyric acid, and azulene), with intermediate activity
      (cinnamic acid and hydroxycinnamic acid), and with high activity (methyl
      propionate and butyric acid). The effect of the interaction of the compounds was
      studied. When acting conjointly, all combinations tested produced a more negative
      effect on both germination and seedling growth than when acting alone. The
      interaction affected cotyledon emergence and root length more negatively than
      germination and cotyledon length. When hydroxycinnamic acid and cinnamic acid
      were added to these mixtures there was an enhancement in the phytotoxic activity,
      accentuating the effect of the other allelochemicals.

PMID- 11441450
TI  - Plant growth inhibiting flavonoids in exudate of Cistus ladanifer and in
      associated soils.
AB  - Of the aglycone flavonoids identified in the exudate of cistus ladanifer, two,
      the flavone apigenin-4'-(O)-methyl and the flavonol kaempferol-3,7-di(O)-methyl
      inhibit development of the seedlings of Rumex crispus at 0.5 and 1 mM. Additive
      effects were observed between the major flavonols of the exudate kaempferol-3-(O)
      methyl and kaempferol-3,7-di-(O)-methyl in inhibiting the size of the cotyledons
      and delaying the germination and cotyledon emergence. The presence of apigenin-4'
      (O)-methyl, kaempferol-3,7-di-(O)-methyl, and kaempferol-3-(O)-methyl was
      detected in the soils associated with C. ladanifer during the summer and autumn
      months. That these compounds are present in the soil and are not restricted to
      the leaves provides support for the hypothesis that C. ladanifer has allelopathic
      potential.

PMID- 11441451
TI  - Dental paleopathology in a Serbian Medieval population.
AB  - Analysis of the pattern of dental disease in two Late Medieval populations from
      cemeteries excavated at archaeological sites in western Serbia was based on the
      study of tooth wear, ante-mortem tooth loss, caries, dental enamel hypoplasia,
      alveolar resorption, abscesses and calculus. The findings reported here show a
      high prevalence of attrition, alveolar resorption and caries, which suggest an
      abrasive diet and poor oral hygiene.

PMID- 11441452
TI  - Social conditioning of body height and mass in children and adolescents, as well
      as in adult inhabitants of the Konin Province, Poland.
AB  - This paper presents the socio-economic conditioning of somatic features in
      children and adolescents, as well as in adults, both men and women. The material
      used in the analysis was collected in 1990 in the Konin voivodeship (Poland). It
      comprises 1587-1608 boys and 2191-2213 girls at the age of 7-18 years. The adults
      consist of two groups: 1. aged 25-39 (3096 men and 4628 women), 2. aged 40-59
      (4210 men and 3061 women). The metrical data comprise body height, body mass and
      BMI. Environmental (size of the district of residence) and social data (level of
      education and professional data of the parents) were taken into account.
      Multidimensional statistical analysis (step-wise) was applied to explain the
      variability of the somatic features under study in relation to the socio
      environmental factors. It could be shown that the socio-environmental
      differentiation of the somatic features manifests itself in a different manner
      depending on the kind of feature, on the gender and on the age. In comparison
      with the girls the boys show a greater ecosensitivity of body height and mass and
      a lesser ecosensitivity concerning the BMI. Among all the factors describing "the
      quality of living conditions" the classically used indirect factors have a
      fundamental influence on the development of body height, body mass and BMI of
      boys, as well as on the body height of girls (e.g. parents' addiction to
      nicotine, physical effort). The social differentiation manifests itself most
      clearly in adult women's body mass and BMI and in men's body height. The level of
      education is a factor of relatively highest importance. It differentiates somatic
      features of men and women independently of their age (exceptions: body mass of
      younger women, BMI of older men). The occupational stratification differentiates
      women's somatic features (with the exception of the BMI of the older women) and
      body height of the younger men. The size of the district differentiates somatic
      features in younger women and men, apart from body height in men, and
      conditionally (Ha: one-sided) BMI in older women.

PMID- 11441453
TI  - Biological age in children who practise swimming.
AB  - In the estimation of the developmental regularity among children it is important
      to know the relation between the developmental and the calendar age. It is
      particularly important in the estimation of the level of development among
      children with an increased level of guided motor activity. It takes place, for
      instance, in the case of children practising swimming. In auxology there are many
      morphological, physiological and motor features which are regarded as the measure
      of the developmental age. For several years researches have been conducted on the
      EMN index as the determinant of the biological age. The EMN index shows
      continuous changes during ontogeny, proves the existence of stages in the
      developmental age and is also considerably correlated with the calendar age. This
      is an ecosensitive factor. The EMN index differentiates individuals from another
      as well as groups isolated with regard to the effect of the environmental
      factors, for instance, the different levels of motor activity. The aim of this
      investigation is to estimate the standard of biological maturity (the body height
      and mass, the EMN index) among children, who went through a guided swimming
      training. Morphological features are most often used as the measures of
      development. However, they can become unreliable when they themselves establish
      the criterion of selection to a sports discipline or when some ranges of values
      are optimal on some given standards. The EMN index is not burdened with these
      features. The children who go through training show the higher level of the EMN
      index values than the children who do not go. The effect of this is the fact that
      young swimmers are biologically older than their peers. However, the shape of the
      curve of development of the EMN index in swimmers goes at a different level
      depending on the seniority of training.

PMID- 11441454
TI  - Anthropometric indices and physical fitness in university undergraduates with
      different physical activity.
AB  - Physical activity and fitness have important health promoting effects with
      respect to arterosclerosis and coronary heart disease in particular. An
      intervention study of physical status and physical activity in university
      undergraduates (University of Tartu) has been carried out. The physically
      inactive (Group I) consisted of 310 undergraduates (235 females and 75 males) of
      the Faculty of Medicine. The physically active (Group II) was recruited from
      among undergraduates (22 females and 23 males) of the Faculty of Exercise and
      Sport Sciences, who participated in training sessions regularly, 3 to 5 times per
      week. Anthropometric body measurements, arm force, vital capacity and exercise
      test on the bicycle ergometer (PWC170) were performed. There were no
      statistically significant differences between the mean values of anthropometric
      indices in case of physically inactive and physically active female subjects. In
      the group of physically active male undergraduates, weight and shoulder width
      were larger than in students with physically sedentary life style (p < 0.05).
      Most of the female and male students had normal BMI. There were statistically
      significant differences in the mean values of vital capacity, arm force and
      aerobic working capacity between the study groups, while physically active
      students had higher physical capacity (p < 0.001). Mean anthropometric indices
      demonstrated a statistically significant increase in both female and male
      university undergraduates after the interval of 30 years. Normal BMI and
      anthropometric indices do not serve a as guarantee of physical fitness for
      university undergraduates who are involved in sedentary life style. Regular
      physical activity has a strong positive impact on physical fitness, particularly
      on aerobic capacity which is the most important health promoting component of
      physical fitness with respect to coronary heart disease.

PMID- 11441455
TI  - Permanent tooth emergence in Gujjars of Punjab, India.
AB  - Patterns of permanent tooth emergence in Gujjars were studied in a cross
      sectional sample of 483 children ranging in age from 6 to 13 years. Females were
      markedly advanced in permanent tooth emergence times over males, but no such sex
      differences were observed in sequence of emergence. Differences between median
      emergence times of right and left side antimers were significant for only 4 of 28
      instances (14.29%), namely central incisors, mandibular first molars in males and
      lateral maxillary incisors in females. In general mandibular teeth except
      premolars tended to emerge earlier than their maxillary counterparts. The
      quiescent period between first and second tooth emergence stages was longer in
      males than in females. Mandibular depth and morphological facial length were very
      significantly correlated (p < 0.01) with the number of permanent teeth present in
      the oral cavity.

PMID- 11441456
TI  - 5th International Ancient DNA Conference, 12-14 July 2000.

PMID- 11441457
TI  - Anthropometric variation in west-central Mexico.
AB  - Anthropometric data from five indigenous Mexican groups, collected by Carlos and
      Manuel Basauri in 1933, were reanalyzed and compared with serological and cranial
      non-metric data. Ten cranial and 14 postcranial measurements were used, both
      separately and together. Bias-corrected r0 and FST values were slightly higher
      for the postcranial analysis (0.033) than for the cranial analysis (0.024). Given
      the degree of linguistic differentiation among the Mexican populations, not to
      mention the different histories of the communities sampled, this result is
      surprisingly low. The two groups which were closest linguistically and
      geographically, the Cora and Huichol, were also close biologically. The other
      three groups, Tarascan, Aztecan, and Otomi, were not closely related to each
      other or to the Cora-Huichol pair. More interesting than the relationship between
      populations in this case are those within them. The Aztecas of Tuxpan, Jalisco,
      exhibit high rii values and lower-than-expected phenotypic variance, suggesting
      the pronounced action of genetic drift. The Otomi of Ixmiquilpan and Cora of the
      Sierra de Nayarit, despite their very different histories, both exhibit low rii
      values and higher-than-expected phenotypic variance, indicating a high level of
      gene flow. Despite the phenotypic similarities between the Cora and Huichol,
      their residual variance is very different; this mirrors serological
      investigations of relative admixture. Over all, recent population history, and
      especially non-indigenous admixture, are at least as explicative of the observed
      biological variation as historical linguistic ties are.

PMID- 11441458
TI  - Killer behaviour in wild wine yeasts associated with Merlot and Malbec type musts
      spontaneously fermented from northwestern Patagonia (Argentina).
AB  - The occurrence of killer wine yeasts in Comahue Region (Patagonia, Argentina) was
      studied. Wild wine yeasts were isolated from spontaneously fermenting Merlot and
      Malbec type musts. Out of 135 isolates analyzed 37% were sensitive to some well
      characterized killer toxins as K1-K10 and did not show killer activity (sensitive
      phenotype, S), 21% showed neutral phenotype (N) and 42% demonstrated killer
      activity (killer phenotype, K). All but two killer strains, identified as Candida
      pulcherrima and Kluyveromyces marxianus, were Saccharomyces cerevisiae.
      Additionally, all killer strains were sensitive to some killer reference strains,
      showing a killer-sensitive phenotype (KS); neither Saccharomyces or non
      Saccharomyces wild yeasts were phenotype killer-resistant (KR). The incidence of
      the killer character varied with respect to fermentation stage and grape variety,
      increasing throughout fermentation (13-55% to 36-90%). Irrespective of grape must
      type, the neutral and sensitive yeasts were ever predominant at initial stages of
      fermentation. All but six neutral strains, identified as Saccharomyces
      cerevisiae, were Kloeckera apiculata.

PMID- 11441459
TI  - Ligninolytic enzyme production in selected sub-tropical white rot fungi under
      different culture conditions.
AB  - Lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase activities in
      selected sub-tropical white rot fungal species from Zimbabwe were determined. The
      enzyme activities were assayed at varying concentrations of C, N and Mn2+.
      Manganese peroxidase and laccase activities were the only expressed activities in
      the fungi under the culture conditions tested. Trametes species, T. cingulata, T.
      elegans and T. pocas produced the highest manganese peroxidase activities in a
      medium containing high carbon and low nitrogen conditions. High nitrogen
      conditions favoured high manganese peroxidase activity in DSPM95, L. velutinus
      and Irpex spp. High manganese peroxidase activity was notable for T. versicolor
      when both carbon and nitrogen in the medium were present at high levels. Laccase
      production by the isolates was highest under conditions of high nitrogen and
      those conditions with both nitrogen and carbon at high concentration. Mn2+
      concentrations between 11-25 ppm gave the highest manganese peroxidase activity
      compared to a concentration of 40 ppm or when there was no Mn2+ added. Laccase
      activity was less influenced by Mn2+ levels. While some laccase activity was
      produced in the absence of Mn2+, the enzyme levels were higher when Mn2+ was
      added to the culture medium.

PMID- 11441460
TI  - Glutathione metabolism and dimorphism in Aureobasidium pullulans.
AB  - Yeast<-->mycelium morphological transitions of Aureobasidium pullulans are
      influenced by numerous environmental factors. In general, changes in the
      glutathione (GSH) metabolism of dimorphic fungi may lead to alterations in the
      reduced thiol status of the cells that are hypothesised to initialise
      morphological transitions. In accordance with this hypothesis, the specific GSH
      levels found in A. pullulans yeast cells were always significantly higher than
      those in mycelia. One the other hand, there was no significant difference between
      the GSH/GSSG redox status of the cells with either yeast or mycelial morphology.
      The cascade of events leading to morphological transitions was therefore unlikely
      to proceed via redox modulation of protein thiols. Although there were morphology
      dependent differences in the specific activities of some GSH metabolic enzymes,
      e.g. glutathione reductase (GR), gamma-glutamyltranspeptidase (gamma GT), glucose
      6-phosphate dehydrogenase (G6PD), they were not satisfactory to explain the
      observed alterations in the intracellular GSH levels. It is noteworthy that very
      similar specific gamma GT and G6PD activities were found in cells separated from
      mixed morphology cultures independently of the actual cell morphology. On the
      other hand, the specific gamma GT and G6PD activities of A. pullulans cells
      sharing the same morphology but separated from pure and mixed morphology cultures
      showed marked differences.

PMID- 11441461
TI  - Penicillin productivity and glutathione-dependent detoxification of phenylacetic
      and phenoxyacetic acids in Penicillium chrysogenum.
AB  - Both toxicity and penicillin productivity of the hydroxylated derivatives of
      phenylacetic acid (PA) and phenoxyacetic acid (POA) were highly dependent on the
      position of hydroxylation on the aromatic ring in Penicillium chrysogenum.
      Hydroxylation at position 2 diminished penicillin production but the compounds
      retained most of their toxicity. On the other hand, hydroxylation at position 4
      resulted in barely toxic derivatives with still significant penicillin
      productivity. 3-Hydroxy-PA was a weak side-chain precursor with considerably
      reduced toxicity. The activity of the glutathione-dependent detoxification
      pathway correlated well with the toxicity of the compounds but there was no
      correlation between acidity, toxicity and penicillin productivity.

PMID- 11441462
TI  - Involvement of gntS in the control of GntI, the main system for gluconate
      metabolism in Escherichia coli.
AB  - The initial steps of gluconate metabolism in E. coli, transport and
      phosphorylation, occur through duplicate activities. These activities have been
      included in two systems designated as GntI (main) and GntII (subsidiary), encoded
      by differently regulated operons located at the 76.4-77 and 95.3-96.9 regions on
      the map respectively. Despite recent molecular advances related to genetics and
      physiology of these systems, there is no information about the coordination of
      their expression when E. coli grows on gluconate. Under these conditions, the
      subsidiary gluconokinase (gntV gene, min 96.8) as well as the GntI activities are
      expressed in inducible form. Therefore it was of interest to find out if GntS,
      the positive regulator of gntV has a similar effect on GntI activities
      expression. Our results agree with this hypothesis. GntS, in addition to its
      regulatory action on the gntV gene, seems to assist, direct or indirectly, the
      expression of the GntI activities. A gntS E. coli mutant does not grow on
      gluconate but spontaneously pseudoreverts to a gluconate growing phenotype at
      high rate per cell generation when cultivated in rich media with or without
      gluconate or mineral medium containing any other suitable carbon source. In the
      pseudorevertants, the thermosensitive gluconokinase remains repressed while the
      GntI activities are inducibly expressed. At present, the location and nature of
      the gntS suppressor mutation are not known. Phage P1Kc mediated transductions
      have ruled out that it alters the gntT gene. This is the first report on GntI
      activities alteration due to a lesion located out of the bioH-asd region.

PMID- 11441463
TI  - Genetic diversity of Bacillus thuringiensis serovars revealed by RFLP using
      random DNA probes.
AB  - EcoRI and HindIII restriction fragment length polymorphism (RFLP) profiles using
      2 random DNA probes, named 104 and 106, were generated for 85 B. thuringiensis
      strains. These include 80 serovars, 4 intra-serovar strains: kurstaki HD-1,
      dendrolimus, tenebrionis and sandiego, and a non-serotypeable strain B.
      thuringiensis var. wuhanensis. A total of 47 EcoRI and 65 HindIII restriction
      patterns were generated when hybridization results from both probes were
      combined. Seventy-seven B. thuringiensis strains showed distinctive hybridization
      profiles. The dendrogram resulting from the numerical analysis of the distance
      matrix revealed fourteen distinct phylogenetic groups at the 96% banding patterns
      similarity. The intra-serovar strains showed higher similarity with their
      respective type serovars. However, different serovars from a common H-serotype
      did not always cluster in the same phylogenetic group. Alternatively, several
      mosquitocidal serovars clustered in a single phylogenetic group. The correlation
      between serotyping and banding pattern similarity is discussed.

PMID- 11441464
TI  - Adenine toxicity and transport in the moderately halophilic eubacterium Halomonas
      elongata.
AB  - The presence of adenine in the L-alanine defined medium substantially inhibited
      the growth of the moderately halophilic eubacterium Halomonas elongata. Extensive
      attempts to reverse the adenine toxicity for growth were made using a variety of
      purine and pyrimidine compounds, vitamins, and amino acids. Of the compounds
      tested, only cytosine was found to reverse the adenine growth inhibition. This
      indicates a mechanism similar to that found for some strains of Escherichia coli
      in which the presence of exogenous purines (e.g. adenine) was found to stop
      purine de novo synthesis and repress the synthesis of the pyrimidine salvage
      enzyme cytosine deaminase. H. elongata was found to possess an active adenine
      uptake system that was sodium dependent with only lithium having a considerable
      capacity to replace the sodium. A competition study indicated that the adenine
      transport system was quite specific. This paper represents the initial study of
      purine and pyrimidine salvage pathways and adenine uptake for the moderately
      halophilic eubacteria.

PMID- 11441465
TI  - [Coping of schizophrenic adolescents].
AB  - The present study examines for the first time specific forms of coping in
      adolescents with schizophrenia during the initial phase of their illness. It was
      found that schizophrenic adolescents develop considerably less active coping
      compared to adolescents with other disorders. Active coping is least prominent
      for positive symptoms (delusions, hallucinations, thought disorders); the
      youngest first-manifestation adolescents are also impaired in other domains
      (irritability, psychosocial stability). The results have exploratory character as
      they are based on a small and thus not representative number of cases, but should
      prompt further investigations.

PMID- 11441466
TI  - [Growing up in changing conditions--on the structural change of childhood and
      adolescence].
AB  - The conditions and patterns of growing up in Germany have undergone a lot of far
      reaching changes. This provides new chances on the one hand; on the other it
      shows some new challenges, which have to be taken into consideration in the field
      of socialization and education. The problems of managing and coping with the
      demands of every day life are nowadays also problems of children and young
      people.

PMID- 11441467
TI  - [Differences in the assessment of 9-14-year-old sons of divorced and not divorced
      parents].
AB  - Twenty-eight 9- to 14 years old boys from divorced families were compared with
      twenty-six 9- to 14 years old boys from two-parent families. Californian Child Q
      Sort assessments (Block and Block 1980) were obtained from themselves, as well as
      from mother, father, a friend, and from the trained interviewer. Boys with
      divorced parents indicated more stress without showing it to others. They longed
      for appreciation from the others, showed lower self-esteem and more helplessness,
      but not more dissocial behavior. Supportive representation of their mother
      correlated positively with ego-resiliency and self-esteem, and negatively with
      helplessness, while others did not seem to notice the boys' helplessness. They
      indicated less dissocial and more social behavior, they were more sensitive and
      had better relations with other children. Supportive representation of fathers
      was beneficial only for the control group. The data correspond to differences in
      quality of narrative language published previously. They are discussed from an
      attachment theory perspective.

PMID- 11441468
TI  - [Adolescent arsonists--psychodynamics, family dynamics and attempt at framing a
      typology based on 40 expert opinions].
AB  - Psychiatric, psychological and medical data of 40 adolescent firesetters are
      obtained from a retrospective analysis of expert opinions which have been drawn
      up by the Department of Child and Adolescent Psychiatry in Tubingen over a period
      of 16 years (1981-1997). This analysis mainly focusses on the patients' physical
      and psychosexual development, their social integration and competence and their
      family dynamics. It further concentrates on the psychic situation at the time of
      the offense, the reasons and motives given for firesetting (by the patient and by
      the expert) and specific psychological test results. According to the results
      three different characteristic groups can be found: 1st a group of offenders who
      have set fires to their parents' house, 2nd firesetters being member of the
      firebrigade, and 3rd an unspecific inhomogeneous group of firesetters.

PMID- 11441469
TI  - Parathyroid imaging: basic principles and KU Leuven experience: MIBI-dual phase
      versus MIBI/I-123.
AB  - OBJECTIVE: The aim of our study was to evaluate and compare retrospectively MIBI
      dual phase and MIBI/I-123 subtraction scintigraphy for preoperative localisation
      of hyperfunctioning parathyroid glands. In our department we also attempted to
      improve the results of the latter method by altering the subtraction technique.
      SUBJECTS AND METHODOLOGY: Fifty-one patients with hyperparathyroidism underwent
      preoperative evaluation with radionuclide scanning for the localisation of
      abnormal parathyroid glands. MIBI-dual phase and MIBI/I-123 subtraction
      scintigraphy were carried out respectively in fourteen and thirty-seven patients.
      Anatomopathological findings were used as the gold standard. RESULTS: Topographic
      identification of the pathological parathyroid glands was correct in 28% for MIBI
      dual phase, in 46% for MIBI/I-123 ('old' method) and in 67.5% for MIBI/I-123
      ('new' method). Relying on a normal histology of the normal parathyroid glands,
      there's a specificity of respectively 82.7%, 99% and 96%. CONCLUSION: MIBI/I-123
      subtraction scintigraphy is superior to MIBI-dual phase for the preoperative
      detection and localisation of hyperfunctioning parathyroid tissue, especially
      when using a gradual subtraction.

PMID- 11441470
TI  - Primary hyperparathyroidism: pathophysiology, diagnosis and indications for
      surgery.
AB  - There is little debate about the primacy of surgery in the management of
      symptomatic or complicated primary hyperparathyroidism. Rather, the question has
      been what to do about the many patients with nonclassical disease. Recent
      prospective data have confirmed that patients with asymptomatic primary
      hyperparathyroidism who are not surgical candidates for parathyroidectomy appear
      to do well when they are managed conservatively. On average, these patients
      remain stable, with little progression to the more serious manifestations of
      hyperparathyroidism over 10 years. It would seem, therefore, that the overall
      population of older patients with mild asymptomatic primary hyperparathyroidism
      can be safely followed without intervention. A certain proportion of cases do
      progress, however, so surveillance is necessary. Individual patients can have
      worsening hypercalcemia or hypercalciuria, and in a small percentage of patients,
      bone density may decrease over time. In most patients, deferral of surgery is not
      a one-time decision, but rather one that is reviewed and reconsidered in
      conjunction with meticulous monitoring.

PMID- 11441471
TI  - Pre- and intra-operative findings in primary hyperparathyroidism.
AB  - The files were studied of 300 patients operated for primary hyperparathyroidism
      for the first time. Their median age was 60 years. The female/male ratio was 3/1,
      but in the younger patients males and females were about equally present.
      Preoperatively, one third was considered as asymptomatic with respect to
      hyperparathyroidism. In this subgroup the hypercalcemia was detected
      coincidentally and the mean parathyroid hormone level was lower than in the
      others. Another third of the patients had nephrolithiasis, they were on the
      average younger and there were more males. Finally one third showed other
      symptoms as gastrointestinal disease, bone disease or general malaise.
      Intraoperatively, we found a solitary adenoma in 90% of the cases, a double
      adenoma in 5% (on each side of the neck in half of the cases) and hyperplasia in
      4%. The adenomas had a tendency to occur more often in the upper parathyroid
      glands, but the difference was not important enough to influence the surgical
      technique. Hyperplasia patients were, on the average, younger and double adenoma
      patients older. The female/male ratio was 1/1 for hyperplasia and 15/1 for double
      adenoma.

PMID- 11441472
TI  - Localization studies for hyperparathyroidism: implications for surgery.
AB  - To localize enlarged parathyroid glands prior to surgery, various non-invasive
      methods are available: ultrasound, CT scan, MRI scan, Thallium-technetium scan
      and especially Sestamibi scan. The paper discusses the usefulness of these
      techniques in the initial exploration and in the re-exploration of primary and
      secondary hyperparathyroidism.

PMID- 11441473
TI  - Peroperative measurement of PTH in the management of primary hyperparathyroidism.
AB  - This study was performed to prospectively evaluate the efficacy of a newly
      developed, non-expensive and non-commercial perioperative PTH-assay as indicator
      of successful surgery in minimally invasive adenomectomy (MIA) for primary
      hyperparathyroidism (pHPT). METHODS: A chemoluminescence-based PTH-assay was
      modified to significantly shorten the incubation time, producing results in a
      total of 45-60 minutes. Its reliability was tested in 19 patients undergoing MIA
      for pHPT. Patients were selected for MIA based on preoperative imaging including
      ultrasound and CT. After verification of its reliability, the PTH assay was
      incorporated into our treatment protocol and its results registered and
      correlated with serum calcium levels and surgical outcome. RESULTS: The PTH assay
      was found to fully correlate with the current gold standard, i.e. serum calcium
      levels on the first postoperative day after MIA. It was subsequently used in 55
      patients selected for MIA, as well as in 26 patients undergoing conventional neck
      exploration (CNE). In all cases it correctly indicated surgical failure/success.
      The conventional re-exploration that was required in 3 patients after
      unsuccessful MIA, was also correctly interpreted on the basis of the PTH-assay.
      In 2 cases an unexpected delay was encountered in the decline of PTH-levels
      following adenomectomy. CONCLUSION: The perioperative PTH-assay described is a
      reliable, inexpensive, and relatively fast predictor of surgical outcome, and
      should be considered essential for minimally invasive surgery in patients with
      pHPT.

PMID- 11441474
TI  - Postoperative course of serum parathyroid hormone and calcium after surgery for
      primary hyperparathyroidism.
AB  - The aim of this study was to describe the course of parathyroid hormone (PTH) and
      serum calcium after surgery for primary hyperparathyroidism, and to evaluate the
      usefulness of daily measurement of these parameters. PTH and serum calcium were
      daily monitored during the early postoperative period in 45 patients where a
      parathyroid adenoma was removed. PTH showed a sharp drop to a very low level
      already on the first postoperative day, whereafter a rapid recovery began. Serum
      calcium decreased more slowly: on the average, the lowest calcium level was seen
      on the second day. A majority of the patients were temporarily hypocalcemic,
      apparently to various degrees. After two weeks 38 patients showed a normal
      calcemia, while six patients remained slightly hypocalcemic. It is concluded that
      after removal of a parathyroid adenoma an abrupt fall of PTH precedes the
      decrease of serum calcium. The first day's PTH level is a reliable indicator of
      the success of the intervention and it should be a major point in the
      postoperative biochemical follow-up. Repeated measurements of serum calcium are
      useful, in contrast with the daily dosage of PTH which can be omitted for
      economical reasons.

PMID- 11441475
TI  - Recent trends in the initial surgical treatment of primary hyperparathyroidism: a
      review.
AB  - INTRODUCTION: The standard treatment of primary hyperparathyroidism has long
      been, and for many surgeons still is, a cervicotomy with presentation of all
      parathyroid glands. The last two decades have been marked by a progress in
      localization and identification techniques, together with a general trend towards
      less invasive surgery. This evolution resulted in numerous and diverging new
      surgical strategies, all claiming to be as effective as the conventional neck
      exploration, but resulting in fewer complications and better cosmesis. We want to
      give an overview and a realistic positioning of these new techniques.
      METHODOLOGY: A literature search using PubMed from January 1980 to December 2000,
      combined with reference checking, identified the most important articles
      describing the new strategies. We present the evolution in the thinking, the data
      supplied, and our critical remarks. RESULTS AND CONCLUSION: The initial random
      unilateral exploration was followed by trials to achieve a more guided unilateral
      exploration. Different adjuncts developed can be classified as preoperative
      (isotope scanning, ultrasonography, computer tomographic scanning) and
      intraoperative (intraoperative intact parathyroid hormone measurement,
      intraoperative 99mTc sestamibi scanning). The surgical techniques using these
      adjuncts range from a classic collar type incision followed by a unilateral
      exploration, over external exploration (unilateral or bilateral) through a very
      small incision, to endoscopic neck exploration. Reported outcomes of these
      techniques are presented, and all aspects mentioned are labeled as T-1
      (preoperative), T0 (intraoperative), or T + 1 (results and complications)
      features. The reported results seem to indicate there is a place for a less
      invasive approach, but should be interpreted with caution seeing the ever present
      selection bias in the described population.

PMID- 11441476
TI  - Reoperation for persistent or recurrent primary hyperparathyroidism.
AB  - The paper gives a summary of the intraoperative findings in 38 patients who
      underwent a reoperation for persistent or recurrent primary hyperparathyroidism.
      The reasons for failure of the first intervention were inexperience of the
      surgeon, ectopic and supernumerary glands, parathyreomatosis and true recurrence.
      Careful localization studies are mandatory in the preoperative work-up of these
      patients.

PMID- 11441477
TI  - Persistent hyperparathyroidism after kidney transplantation requiring
      parathyroidectomy.
AB  - INTRODUCTION: Successful kidney transplantation (KT) is believed to cure
      secondary hyperparathyroidism, but persistent disease has emerged in a
      significant number of allograft recipients. Parathyroidectomy (PTX) is ultimately
      required in some of these patients. AIM: To provide an in-depth analysis of 42
      patients who required surgical treatment for persistent hyperparathyroidism after
      successful renal transplantation and to identify risk factors for PTX present at
      the time of transplantation. DESIGN: Retrospective case controlled study.
      METHODS: Charts of 1332 kidney allograft recipients, transplanted between 1989
      and 2000, were reviewed. Patients requiring a PTX after a first successful kidney
      transplantation (serum creatinine < 2.5 mg/dl) were identified. Their charts were
      checked for various demographic, clinical and biochemical variables. The data
      were compared with data obtained from a control group closely matched for time of
      transplantation. RESULTS: Persistent hyperparathyroidism after successful KT
      requiring PTX occurred in 55 (4.1%) patients. Because of insufficient follow-up
      data only 42 recipients were eligible for further analysis. The age of the
      patients was 52 +/- 2.1 years (mean +/- SEM). The time between transplantation
      and PTX was 416 +/- 61 days. The mean serum creatinine at the time of PTX
      amounted to 1.6 +/- 0.1 mg/dl. Persistent hypercalcemia, albeit asymptomatic in
      most patients, was the main indication for PTX. Enlarged parathyroid glands were
      visualised by ultrasonography in 74% of the cases. Subtotal parathyroidectomy was
      the procedure of choice. The operative morbidity was negligible and the incidence
      of persistent or recurrent hyperparathyroidism was low, being 15%. In comparison
      to the control group, the patients with persistent hyperparathyroidism had a
      significant longer duration of pre-transplantation dialysis treatment (36.3 vs.
      23.0 months, p < 0.01) and significant higher values of intact parathyroid
      hormone (iPTH) (268.1 vs. 96.0 ng/l, p < 0.001), total serum calcium (10.6 vs.
      9.4 mg/dl, p < 0.001), and serum alkaline phosphatases (185.5 vs. 132.0 U/L, p <
      0.001) at the time of transplantation. No relationship with the mode of dialysis
      treatment was observed. CONCLUSION: Persistent hyperparathyroidism requiring PTX
      after successful KT is a common clinical problem. Patients who spent a long time
      on dialysis and/or patients with a high pre-transplant level of iPTH, serum
      calcium and alkaline phosphatases are especially at risk.

PMID- 11441478
TI  - Parathyroid function in the early postoperative period after thyroidectomy.
AB  - Serum levels of parathyroid hormone (PTH) and calcium were studied in 132
      patients, divided into three groups: unilateral thyroid-lobectomy, (sub)total
      thyroidectomy for non-toxic goitre and (sub)total thyroidectomy for
      hyperthyroidism. It was found that all types of thyroidectomy, even unilateral
      lobectomy, had a temporary influence on the PTH and calcium metabolism in the
      early postoperative period, albeit to different degrees. The effect was most
      pronounced after surgery for hyperthyroidism, which carries the greatest risk for
      postoperative hypocalcemia. The pathogenesis of transient postoperative
      hypocalcemia as well as the implications for the surgical management are
      discussed.

PMID- 11441479
TI  - Historical note: the beginning of parathyroidectomy.
AB  - The paper describes briefly the major historical steps towards the development of
      the surgical treatment of hyperparathyroidism. The first parathyroidectomies were
      carried out in 1925, in Europe and in the United States, independently from each
      other. The first surgeon in Vienna, F. Mandle, has received a rightly deserved
      place in the history of medicine, while in Boston the first patient is reminded
      mostly.

PMID- 11441480
TI  - Anatomy and embryology of the parathyroid glands.
AB  - The embryology and anatomy of the parathyroid glands is described and the
      implications for surgery are discussed.

PMID- 11441481
TI  - Histopathology of the parathyroid glands.
AB  - The paper describes the histology of the normal parathyroid gland and the
      histopathology of parathyroid adenoma, hyperplasia and carcinoma. The
      possibilities and limitations of intraoperative frozen sections are discussed.
      Finally the use of immunochemistry and other special studies in parathyroid
      pathology is mentioned.

PMID- 11441482
TI  - Conformational and quantum analysis of dental adhesive carboxylic acid and
      carboxylic acid anhydride monomers.
AB  - The conformational and quantum analyses of dental adhesive carboxylic acid and
      carboxylic acid anhydride monomers were preformed. Conformational analyses were
      carried out by a molecular mechanics calculation. 4-META and 4-AETA showed more
      compact conformation than 4-MET. Quantum analyses were performed by semi
      empirical molecular orbital calculation. 4-MET had a higher dipole moment,
      polarizability, and HOMO and LUMO energy than 4-META and 4-AETA. The bond lengths
      and bond orders of the carbonyl groups of the trimellitic acid moiety of 4-MET
      were different from those of carbonyl groups of the trimellitate anhydride
      moieties of 4-META and 4-AETA. Oxygen of the methacryloyl or acryloyl groups
      showed the highest electron densities among the oxygen atoms for all monomers.
      The superdelocalizabilities of oxygen atoms of the trimellitic acid moiety of 4
      MET were greater than that of oxygen of the methacryloyl group. A small change in
      the bond length of the Ca-O bond showed a large difference in the steric energies
      of 4-MET/Ca salt.

PMID- 11441483
TI  - Corrosion behavior and surface structure of orthodontic Ni-Ti alloy wires.
AB  - The corrosion behaviors of a commercial Ni-Ti alloy orthodontic wire and a
      polished plate with same composition in 0.9% NaCl and 1% lactic acid solutions
      were examined using an electrochemical technique, an analysis of released ions,
      and a surface analysis by X-ray photoelectron spectroscopy (XPS). The effect of
      polishing the wire on the corrosion was also examined. The XPS analysis
      demonstrated the presence of a thick oxide film mainly composed of TiO2 with
      trace amounts of Ni hydroxide, which had formed on the wire surface during the
      heat treatment and subsequent pickling processes. This oxide layer contributed to
      the higher resistance of the as-received wire to both general and localized
      corrosion in 0.9% NaCl solution, compared with that of the polished plate and the
      polished wire. The thick oxide layer, however, was not stable and did not protect
      the orthodontic wire from corrosion in 0.1% lactic acid solution.

PMID- 11441484
TI  - Study of the fluoridated adhesive resin cement--fluoride release, fluoride uptake
      and acid resistance of tooth structures.
AB  - The objectives of this study, were to evaluate the fluoride release from
      fluoridate adhesive resin cement, fluoride uptake into surrounding tooth
      structures and the effect of their acid resistance. Several specimens were
      prepared using a plastic ring mould, from extracted human premolars, and prepared
      from enamel and dentin of the central area of the buccal surface of bovine teeth.
      The fluoride release rate of fluoridate adhesive resin cement (PN 200) per day
      was higher than other materials during the 7-day study period. Fluoride released
      and fluoride uptake by tooth structures was higher in the fluoridate adhesive
      resin cement. WDX analysis showed the fluoride concentration on dentin contact
      area was higher than that of enamel after 60 days of immersion in deionized
      water. The calcium release values were similar for enamel and dentin plates in
      the various test materials. The present findings indicated the important
      enhancement of tooth structure acid resistance by fluoridate material.

PMID- 11441485
TI  - Casting accuracy of experimental Ti-Cu alloys.
AB  - The purpose of the present study was to investigate the casting accuracy and the
      dimensional change of experimental titanium-copper alloys (3.0 and 5.0 mass% Cu;
      hereafter, only "%" will be used) and to compare the findings with those of pure
      titanium. Castings were made using an argon-arc melting/pressure difference
      casting unit. The fit of the metals cast in both full crown and MOD inlay dies
      was evaluated by measuring the distance between the shoulder margin and the
      cervical shoulder of the die. The changes in the inner diameter of castings were
      determined. In addition, surface roughness measurements inside the castings were
      carried out using a conventional profilometer, and thermal expansion measurements
      were made on cast cylindrical specimens using a differential dilatometer. There
      were no significant differences in dimensional change between pure titanium and
      the titanium-copper alloys. The fit of the titanium-copper alloys was inferior to
      pure titanium. The results of surface roughness measurements showed significance
      differences between the roughness of the pure titanium and titanium-copper
      alloys.

PMID- 11441486
TI  - Effect of NaClO treatment on bonding to root canal dentin using a new evaluation
      method.
AB  - The purposes of this study were to investigate the reliability and efficiency of
      a new evaluation method for resin bonding to root canal dentin, which measures
      both marginal adaptation and shear bond strength simultaneously, and to determine
      the effects of root canal irrigants on resin bonding. A wet bonding system
      (Single Bond) and a self-etching primer system (Clearfil Mega Bond) were
      employed; NaClO was used as a root canal irrigant. No gaps or changes in bond
      strength were observed despite the NaClO treatment when the wet bonding system
      was employed, while the gap formation ratio increased, and bond strength
      decreased with longer NaClO treatment time when the self-etching primer system
      was employed. These findings suggested that this new experimental method was
      effective for evaluating resin systems to the root canal wall dentin which is
      affected by irrigation with NaClO.

PMID- 11441487
TI  - Microstructure and corrosion behavior of binary titanium alloys with beta
      stabilizing elements.
AB  - Binary titanium alloys with the beta-stabilizing elements of Co, Cr, Cu, Fe, Mn
      and Pd (up to 30%) and Ag (up to 45%) were examined through metallographic
      observation and X-ray diffractometry to determine whether beta phases that are
      advantageous for dental use could be retained. Corrosion behavior was also
      investigated electrochemically and discussed thermodynamically. Some cast alloys
      with Co, Cr, Fe, Mn, and Pd retained the beta phase, whereas those with Ag and Cu
      had no beta phase. In some alloys, an intermetallic compound formed, based on
      information from the phase diagram. The corrosion resistance deteriorated in the
      TiAg alloys because Ti2Ag and/or TiAg intermetallic compounds preferentially
      dissolved in 0.9% NaCl solution. On the other hand, the remaining titanium alloys
      became easily passive and revealed good corrosion resistance similar to pure
      titanium since their matrices seemed to thermodynamically form titanium oxides as
      did pure titanium.

PMID- 11441488
TI  - Effects of polysiloxane coating of NaF on the release profile of fluoride ion
      from Bis-GMA/TEGDMA resin containing NaF.
AB  - The aim of this study was to regulate fluoride release from restorative resin
      containing NaF using N-(beta-aminoethyl)-gamma-aminopropylmethyldimethoxysilane
      (AMMS) and evaluate factors that regulate fluoride release from the resin. ESCA
      analysis, FT-IR measurements along with SEM observations demonstrated that a
      polysiloxane layer was formed on the surface of NaF treated with AMMS. Bis
      GMA/TEGDMA resin containing NaF powder treated with AMMS released lower
      concentrations of fluoride for longer periods when compared with that containing
      untreated NaF. However, AMMS treatment of NaF was less effective for the
      regulation of fluoride released from the resin than gamma
      methacryloxypropyltrimethoxysilane (gamma-MPTS) treatment, despite its higher
      hydrophobic polysiloxane layer formation. These findings may have been caused by
      the higher density of polysiloxane prepared with gamma-MPTS than that prepared
      with AMMS. The present findings suggested, therefore, that alkoxysilane should be
      chosen based not only on hydrophobicity but also the density of polysiloxane to
      effectively regulate fluoride release from the restorative resin containing NaF.

PMID- 11441489
TI  - Mechanism of adhesion between 4-META resin and alloys based on Bolger's acid-base
      interaction.
AB  - The water durability at adhesion interfaces between 4-META resin and Au-In or Au
      Si alloys was investigated by the peeling test and by surface analysis using X
      ray photoelectron spectroscopy (XPS) as well as theoretical consideration based
      on Bolger's acid-base theory. XPS spectra demonstrated that several-nm thick
      layers of In2O3 and SiO2 were formed on the Au-In and Au-Si alloys. The water
      durability of the Au-In alloys increased with increases in In content. The Au-Si
      alloy and quartz glass specimens showed a total absence of water durability.
      Bolger's theory suggested that the interaction of 4-MET with In2O3 was considered
      to be ionic and stable in the presence of water while that of 4-MET with SiO2 was
      due to hydrogen bonds, which can easily be dissociated in the presence of water.
      These findings suggest that Bolger's theory is useful for evaluating chemical
      interactions between an adhesive monomer and oxides on a precious metal alloy.

PMID- 11441490
TI  - Corrosion behavior of dental alloys coupled with titanium. Part 2. The area ratio
      dependence in five solutions.
AB  - Sixteen alloys and five pure metals were used and the open circuit potentials
      (OCP) and the coupled potentials with titanium were measured in five kinds of
      solutions. All alloys and metals showed the maximum OCP in 1.3% lactic acid
      solution, and the minimum in 0.01% sodium sulfide solution. The coupled potential
      depended on the area ratio (alloy/titanium). This dependence was different in
      every solution. From the area ratio dependence of the coupled potential, the
      potassium fluoride solution was thought to be active with pure titanium. In
      contrast, sodium sulfide solution was thought to be active with the alloys and
      the metals. The effect of the co-existence of pure titanium was very small in the
      sodium sulfide solution.

PMID- 11441491
TI  - XPS study on the weakest zone in the adhesion structure between resin containing
      4-META and precious metal alloys treated with different surface modification
      methods.
AB  - Three precious metal alloys, Type IV gold alloy, 14 K gold alloy, and silver
      based alloy, were treated with different surface modifications including a metal
      primer (VBATDT) application, a SiOx coating method, high-temperature oxidation,
      modification method with a liquid Ga-Sn alloy, and tin electroplating. Then thin
      PMMA films were bonded with a resin containing 4-META. Water durability at the
      adhesion interface was evaluated after water immersion, followed by thermal
      cycling used liquid nitrogen. The weakest zone at the interface was investigated
      using XPS only for the Ag-Pd alloy specimens that had been surface-treated with
      as-polishing, adhesive primer, and the SiOx coating method, since peeling of the
      PMMA film on the surface of specimens surface-treated by other methods was not
      observed. Metal elements were detected from the resin side at the adhesion
      interface. The chemical states of Cu in the resin before argon ion etching were
      characterized as metal oxides and/or states of chemical interaction with 4-META,
      VBATDT, or SiOx.

PMID- 11441492
TI  - Potential effects of oral infections on systemic health.

PMID- 11441493
TI  - Women in AO: an Australian perspective.

PMID- 11441494
TI  - It's about time.

PMID- 11441497
TI  - Women in the early history of genetics. William Bateson and the Newnham College
      Mendelians, 1900-1910.
AB  - William Bateson was one of the pivotal figures in the early history of genetics,
      having championed the promise of Mendelism to unravel the secrets of heredity.
      Many refer to the "school" of genetics he directed at Cambridge between 1900 and
      1910, but few note that Bateson's group consisted primarily of women. Bateson
      turned to botanists, zoologists, and physiologists associated with Newnham
      College, Cambridge, for critical assistance in advancing his research program at
      a time when Mendelism was not yet recognized as a legitimate field of study.
      Cambridge women carried out a series of breeding experiments in a number of plant
      and animal species between 1902 and 1910, the results of which provided crucial
      evidence that both supported and extended Mendel's laws of heredity. This essay
      shows how the situation of women in science in the early twentieth century was a
      factor--along with scientific, institutional, social, and political developments-
      in establishing the new discipline of genetics.

PMID- 11441499
TI  - Immunoelectron microscopic localization of partially purified antigens in adult
      Paragonimus iloktsuenesis.
AB  - An immunoelectron microscopy employing immunogold labeling method was performed
      to detect tissue origin of D1 fraction (D1A) among 5 antigenic protein fractions
      partially purified by DEAE-anion exchange chromatography from water-soluble crude
      antigen (PIWA) of adult Paragonimus iloktsuenensis. Immune reactions of adult
      worm tissues with rabbit serum immunoglobulin immunized with crude antigen (PI
      Ig) and D1 antigen (D1-Ig), as well as rat serum immunoglobulin infected with P.
      iloktsuenensis were observed. D1A showed strong antigenicity in the intestinal
      epithelium of the worms during the early infection period of 2-4 weeks after
      infection. The vitellaria also showed stronger antigenicity than the other tissue
      sites in immune reaction of tissues against all immunoglobulins from 4 to 33
      weeks after vitelline development. Therefore, it is suggested that D1A was mainly
      originated from the intestinal epithelial tissues before the development of
      vitelline gland of the parasites. Immuno-reactivity of two immunoglobulins (PI
      Ig, D1-Ig) was significantly different in intestinal epithelial cytoplasmic
      protrusions (CP) and intestinal epithelial secretory granules (SG). In the
      experimental group with D1-Ig, gold particles were labeled significantly in CP
      than in SG when compared to the PI-Ig group. Thus, the major antigenic materials
      in D1 antigen having a strong antigenicity in the early infection period was
      considered to be originated from the intestinal epithelial tissue.

PMID- 11441500
TI  - Molecular cloning and characterization of peroxiredoxin from Toxoplasma gondii.
AB  - A cDNA of 1.1 kb comprising the gene encoding the peroxiredoxin of Toxoplasma
      gondii (TgPrx) has been cloned. The open reading frame of 591 bp was translated
      into a protein of 196 amino acids with a molecular mass of 25 kDa. Conserved 2
      cysteine domains of Phe-Val-Cys-Pro and Glu-Val-Cys-Pro indicated TgPrx belonged
      to 2-Cys Prx families. TgPrx showed the highest homology with that of Arabidopsis
      thaliana by 53.9% followed by Entamoeba histolytica with 39.5% by the amino acid
      sequence alignment. Polyclonal antibody against recombinant TgPrx detected 25 kDa
      band in T. gondii without binding to host cell proteins. TgPrx was located in the
      cytoplasm of T. gondii extracellularly or intracellularly by immunofluorescence
      assay. The expression of TgPrx was increased as early as 30 min after the
      treatment with artemisinin in the intracellular stage, while no changes in those
      of host Prx I and TgSOD. This result implies that TgPrx may function as an
      antioxidant protecting the cell from the attack of reactive oxygen intermediates.
      It is also suggested that TgPrx is a possible target of chemotherapy.

PMID- 11441501
TI  - Analysis of polymorphic regions of Plasmodium vivax Duffy binding protein of
      Korean isolates.
AB  - The present study was designed to investigate polymorphism in Duffy binding
      protein (DBP) gene of Plasmodium vivax isolates of Korea. Thirty samples were
      obtained from P. vivax patients in Yonchon-gun, Kyonggi-do in 1998. The PCR
      products of the samples were subjected to sequencing and hybridization analyses
      of the regions II and IV of P. vivax DBP gene. Two genotypes, SK-1 and SK-2, were
      identified on the basis of amino acid substitution and deletion. The genotype of
      10 isolates was SK-1 and that of 20 isolates was SK-2. Most of the predicted
      amino acids in the region II of DBP gene were conserved between the Korean
      isolates and Belem strain except for 4-5 amino acid substitutions. In the region
      IV of DBP, a 6-bp insert that was shown in the Sal-1 allele type was found in SK
      1, and a 27-bp insert that was shown in the Papua New Guinea allele type was
      found in SK-2. In conclusion, the present findings suggest that two genotypes of
      P. vivax coexist in the endemic area of Korea.

PMID- 11441502
TI  - Expressed sequence tags (ESTs) analysis of Acanthamoeba healyi.
AB  - Randomly selected 435 clones from Acanthamoeba healyi cDNA library were sequenced
      and a total of 387 expressed sequence tags (ESTs) had been generated. Based on
      the results of BLAST search, 130 clones (34.4%) were identified as the genes
      encoding surface proteins, enzymes for DNA, energy production or other
      metabolism, kinases and phosphatases, protease, proteins for signal transduction,
      structural and cytoskeletal proteins, cell cycle related proteins, transcription
      factors, transcription and translational machineries, and transporter proteins.
      Most of the genes (88.5%) are newly identified in the genus Acanthamoeba.
      Although 15 clones matched the genes of Acanthamoeba located in the public
      databases, twelve clones were actin gene which was the most frequently expressed
      gene in this study. These ESTs of Acanthamoeba would give valuable information to
      study the organism as a model system for biological investigations such as
      cytoskeleton or cell movement, signal transduction, transcriptional and
      translational regulations. These results would also provide clues to elucidate
      factors for pathogenesis in human granulomatous amoebic encephalitis or keratitis
      by Acanthamoeba.

PMID- 11441503
TI  - Genetic analyses of Acanthamoeba isolates from contact lens storage cases of
      students in Seoul, Korea.
AB  - We conducted both the small subunit ribosomal DNA (SSU rDNA) polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and mitochondrial
      (mt) DNA RFLP analyses for a genetic characterization of Acanthamoeba isolates
      from contact lens storage cases of students in Seoul, Korea. Twenty-three strains
      of Acanthamoeba from the American Type Culture Collection and twelve clinical
      isolates from Korean patients were used as reference strains. Thirty-nine
      isolates from contact lens storage cases were classified into seven types
      (KA/LS1, KA/LS2, KA/LS4, KA/LS5, KA/LS7, KA/LS18, KA/LS31). Four types (KA/LS1,
      KA/LS2, KA/LS5, KA/LS18) including 33 isolates were regarded as A. castellanii
      complex by riboprints. KA/LS1 type was the most predominant (51.3%) in the
      present survey area, followed by KA/LS2 (20.9%), and KA/LS5 (7.7%) types. Amoebae
      of KA/LS1 type had the same mtDNA RFLP and riboprint patterns as KA/E2 and KA/E12
      strains, clinical isolates from Korean keratitis patients. Amoebae of KA/LS2 type
      had the identical mtDNA RFLP patterns with A. castellanii Ma strain, a corneal
      isolate from an American patient as amoebae of KA/LS5 type, with KA/E3 and KA/E8
      strains from other Korean keratitis patients. Amoebae of KA/LS18 type had
      identical patterns with JAC/E1, an ocular isolate from a Japanese patient. Three
      types, which remain unidentified at species level, were not corresponded with any
      clinical isolate in their mtDNA RFLP and riboprint patterns. Out of 39 isolates
      analyzed in this study, mtDNA RFLP and riboprint patterns of 33 isolates (84.6%)
      were identical to already known clinical isolates, and therefore, they may be
      regarded as potentially keratopathogenic. These results suggest that contact lens
      wearers in Seoul should pay more attention to hygienic maintenance of contact
      lens storage cases for the prevention of Acanthamoeba keratitis.

PMID- 11441504
TI  - Western blot diagnosis of vivax malaria with multiple stage-specific antigens of
      the parasite.
AB  - Western blot analysis was performed to diagnose vivax malaria using stage
      specific recombinant antigens. Genomic DNA from the whole blood of a malaria
      patient was used as templates to amplify the coding regions for the antigenic
      domains of circumsporozoite protein (CSP-1), merozoite surface protein (MSP-1),
      apical merozoite antigen (AMA-1), serine repeat antigen (SERA), and exported
      antigen (EXP-1) of Plasmodium vivax. Each amplified DNA fragment was inserted
      into a pGEX-4T plasmid to induce the expression of GST fusion protein in
      Escherichia coli by IPTG. The bacterial cell extracts were separated on 10% SDS
      PAGE followed by western blot analysis with patient sera which was confirmed by
      blood smear examination. When applied with patient sera, 147 (91.9%) out of 160
      vivax malaria, 12 (92.3%) out of 13 falciparum malaria, and all 9
      vivax/falciparum mixed malaria reacted with at least one antigen, while no
      reactions occurred with 20 normal uninfected sera. In the case of vivax malaria,
      CSP-1 reacted with 128 (80.0%) sera, MSP-1 with 102 (63.8%), AMA-1 with 128
      (80.0%), SERA with 115 (71.9%), and EXP-1 with 89 (55.6%), respectively. We
      obtained higher detection rates when using 5 antigens (91.9%) rather than using
      each antigen solely (55.6-80%), a combination of 2 (76.3-87.5%), 3 (85.6-90.6%),
      or 4 antigens (89.4-91.3%). This method can be applied to serological diagnosis,
      mass screening in endemic regions, or safety test in transfusion of prevalent
      vivax malaria.

PMID- 11441505
TI  - Experimental infection of Anopheles sinensis with Korean isolates of Plasmodium
      vivax.
AB  - The objectives of the present study were to (1) determine the susceptibility of
      Anopheles sinensis to Korean isolates of Plasmodium vivax, (2) establish a method
      to collect large quantities of P. vivax sporozoites for use as antigen in
      seroepidemiological studies, and (3) investigate the characteristics of Korean
      isolates of P. vivax sporozoites. Females of Anopheles sinensis were collected at
      non-epidemic area, Seokwha-ri, Cheongwon-gun and Chungcheongbuk-do using tent
      trap methods coupled with dry ice. The females were artificially infected with
      gametocytes of P. vivax using blood obtained from P. vivax malaria patients.
      Individual mosquitoes were infected using either a parafilm-covered glass feeding
      apparatus or were allowed to feed on naturally infected volunteers. Mosquitoes
      were sacrificed between 16 and 18 days post-feeding and an enzyme-linked
      immunosorbent assay (ELISA) was used to detect sporozoites. Four (33.4%) of 12
      mosquitoes, which were fed on naturally infected volunteers directly, were
      positive for sporozoites. In cases, the mosquitoes allowed to feed on whole blood
      which were extract from three different patients with heparin treated
      vacuutainers using a parafilm-covered glass apparatus. Two of 55 (3.6%) were
      positive which blood sample was maintained at room temperature for 8 hours, 1 of
      68 (1.5%) was positive which blood was maintained at 4 degrees C for 24 hours and
      1 of 47 (2.3%) was positive at 4 degrees C for 48 hours. The mean number of
      sporozoites was estimated about 818 (n = 8; range of 648-1,056) based on optical
      density values of ELISA.

PMID- 11441506
TI  - Malaria transmission potential by Anopheles sinensis in the Republic of Korea.
AB  - To evaluate the factors that determine the transmission level of vivax malaria
      using vectorial capacity, entomological surveys were conducted from June to
      August, 2000. From 6 nights of human-bait collection in Paju, the human biting
      rate (ma) was counted as 87.5 bites/man/night. The parity of Anopheles sinensis
      from human baiting collections fluctuated from 41% to 71% (average 48.8%) of
      which the rate gradually increased as time passed on: 35.2% in Jun.; 55.0% in
      July; 66.2% in Aug. From this proportion of parous, we could estimate the
      probability of daily survival rate of An. sinensis to be 0.79 assumed with 3 days
      gonotrophic cycle and the expectancy of infective life through 11 days could be
      defined as 0.073. Blood meal analysis was performed using ELISA to determine the
      blood meal source. Only 0.8% of blood meals were from human hosts. We could
      conclude that An. sinensis is highly zoophilic (cow 61.8%). Malaria is highly
      unstable (stability index < 0.5) in this area. From these data, vectorial
      capacity (VC) was determined to be 0.081. In spite of a high human biting rate
      (ma), malaria transmission potential is very low due to a low human blood index.
      Therefore, we could conclude that malaria transmission by An. sinensis is
      resulted by high population density, not by high transmission potential. For this
      reason, we need more effort to decrease vector population and vector-human
      contact to eradicate malaria in Korea.

PMID- 11441507
TI  - A human case of gastric infection by Pseudoterranova decipiens larva.
AB  - We report a case of gastric pseudoterranoviasis proven by gastrofiberscopy on
      Dec. 13, 1994. The 34-year-old male patient, residing in Chungju-shi, was
      admitted to Konkuk University Hospital complaining of prickling epigastric pain.
      The symptoms suddenly attacked him two days after eating raw marine fish at
      Chonan-shi. By the gastrofiberscopic examination, a long white-yellowish nematode
      was found from the fundus region of stomach. The worm was 34.50 x 0.84 mm in
      size, and was identified as a 3rd stage larva of Pseudoterranova decipiens
      judging from the position of the intestinal cecum. This is the 12th confirmed
      case of human pseudoterranoviasis in Korea.

PMID- 11441508
TI  - Prevalence of arthropod antibodies in Korean patients with allergic rhinitis.
AB  - Arthropod antigens are main causative agents which induce allergic responses in
      humans. However, little information is known about the prevalence of specific
      arthropod allergens in Koreans with allergic diseases. The current study was
      designed to determine the positive rates of arthropod antibodies by the Korean
      inhalant panel of MAST-CLA. One hundred sixty patients, who were diagnosed with
      allergic rhinitis from an out-patient center at the Soonchunhyang University
      Chunan Hospital, were studied between August 1998 to July 2000. The overall
      positive rate, at least more than one specific antibody of arthropods such as
      Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), and cockroach
      mix (Cm), was 46.9%. Each positive rate of Df, Dp, and Cm was 45.0%, 43.1%, and
      8.8%, respectively. A significant agreement among arthropod allergens was
      observed (Df and Dp: 95.6%, Kappa = 0.911, P < 0.001). Our data supported the
      fact that arthropods were the most common allergens in Korean patients with
      allergic rhinitis; however, the MAST-CLA should be modified to increase
      specificity of arthropod allergens.

PMID- 11441509
TI  - An epidemiological survey on Cryptosporidium parvum infection of inhabitants in
      Chorwon-gun, Kangwon-do.
AB  - The present study was undertaken to know the infection status of Cryptosporidium
      parvum among the residents of Chorwon-gun, Kangwon-do in 1993. Total 461 fecal
      samples were collected from the inhabitants residing in Chorwon-gun during the
      period of August 12 to September 14, 1993. Fecal smears were prepared by formalin
      ether sedimentation, and examined after modified acid fast staining. Of the 461
      fecal samples, 9 (1.9%) were positive for C. parvum oocysts. The positive cases
      were limited to thirties (4) patients, forties (3), and sixties (2), and no
      oocyst was detected in other age groups. The oocyst positive rate for male was
      1.4% and that of female was 2.6%.

PMID- 11441510
TI  - A review of Gymnophalloides seoi (Digenea: Gymnophallidae) and human infections
      in the Republic of Korea.
AB  - Studies on Gymnophalloides seoi (Digenea: Gymnophallidae) and human infections
      are briefly reviewed. This minute intestinal fluke was first discovered from a
      Korean woman suffering from acute pancreatitis and gastrointestinal troubles. It
      was described as a new species by Lee, Chai and Hong in 1993. The southwestern
      coastal village where the patient resided was found to be a highly endemic area,
      and additional endemic areas have been identified. The parasite is very small,
      0.33-0.50 mm long and 0.23-0.33 mm wide, and characterized by the presence of a
      ventral pit. The first intermediate host remains unknown, but the second
      intermediate host has been found to be the oyster Crassostrea gigas. Man and the
      Palearctic oystercatcher Haematopus ostralegus have been shown to be natural
      definitive hosts, and wading birds including the Kentish plover Charadrius
      alexandrinus are highly susceptible to experimental infection. Gerbils, hamsters,
      cats, and several strains of mice were also susceptible laboratory hosts. In
      experimentally infected mice, the parasites inhabit the small intestine, pinching
      and sucking the root of villi with their large oral suckers, but they did not
      invade beyond the mucosa in immunocompetent mice. However, they were found to
      invade the submucosa in immunosuppressed mice. Human G. seoi infections have been
      found in at least 25 localities; 23 islands on the Yellow Sea or the South Sea,
      and 2 western coastal villages. The highest prevalence was found in a village on
      Aphaedo, Shinan-gun (49% egg positive rate); other areas showed 0.8-25.3%
      prevalence. Infected people complained of variable degrees of gastrointestinal
      troubles and indigestion. The infection can be diagnosed by recovery of eggs in
      the feces; however, an expert is needed to identify the eggs. Praziquantel, 10
      mg/kg in single dose, is effective for treatment of human infections. Eating raw
      oysters in endemic areas should be avoided.

PMID- 11441511
TI  - Early childhood traumatic development and its impact on gender identity.
AB  - The author clarifies issues of gender identity typical to contemporary Western
      societies. Nowadays, we tend to emphasize self-autonomy as the main target of the
      individual's development. In adolescence this may cause many questions as to the
      adolescent's conception of his or her gender and sexual identity. These questions
      are the outcome of early development, and thus early traumas may impact the
      entire gender development. In this context, trauma includes not only major
      violations such as sexual abuse, terror attacks, and so forth, but also comprises
      events heretofore considered minor.

PMID- 11441512
TI  - Trauma and deferred action in the reality of adolescence.
AB  - In the search for ever earlier determinants of adult pathology many ignore the
      transformative impact of adolescence. The authors suggest that the reality of
      adolescent development creates a vulnerability to being overwhelmed. Through
      deferred action childhood experiences may interact with adolescent realities and
      omnipotent beliefs to traumatize the adolescent. The authors suggest that trauma
      in adolescence can be independent both of the intensity of current external
      exposure or of earlier traumatic experiences.

PMID- 11441513
TI  - Psychological trauma in adolescence: familial disillusionment and loss of
      personal identity.
AB  - This article presents trauma theory and characteristics of traumatized
      adolescents. A case vignette demonstrates the considerations regarding assessment
      and treatment strategies in clinical work with an adolescent girl who suffered
      profound trauma, loss of personal identity, and self-esteem due to familial
      disillusionment. In contrast, the author presents the case of a female Holocaust
      survivor, documenting catastrophic loss, also during adolescence. Irrespective of
      the nature and magnitude of trauma, the single most outstanding predictor of
      future positive adjustment and resilience was the nature of the parent-child tie.

PMID- 11441514
TI  - Dangerous transitions and the traumatized adolescent.
AB  - One of the developmental tasks for the adolescent is to construct a new
      transitional space that leads to internal changes and adapts to the external
      world. When a nurturing matrix is unavailable, adolescents experience the
      entrance into the adult world as a dangerous transition. The author bases his
      arguments on psychoanalytic theories, mostly Winnicott's, and illustrates these
      with clinical material. He suggests that, even though these traumatized
      adolescents experienced nonfunctional transitional spaces, it is proven that they
      could be treated psychoanalytically. Here, the main task of the analyst is to
      establish a holding environment as a type of transference, resulting in less
      emphasis on interpretation of inner conflicts.

PMID- 11441515
TI  - A witness breaks his silence: the meaning of a therapist's response to an
      adolescent's self-destruction.
AB  - I describe the case of a self-mutilating adolescent girl and my dilemma, as her
      therapist, about telling her parents about her self-abuse. I use two
      complementary, mutually enhancing relational theories of trauma--Ferenczi's
      (1933) and Davies and Frawley's (1994)--to help understand the minefield I was
      in. Davies and Frawley describe certain relational configurations that are
      typical of trauma victims. I believe that it is not only unavoidable but
      therapeutically vital for therapists to participate in these configurations so
      they can know the patient's experience in a personal way. It is also crucial that
      they be witnesses who provide recognition for the patient's pain and, in so
      doing, relieve the intolerable feeling of isolation that Ferenczi proposed was
      the most basic trauma. In addition, I discuss the observation that some people
      who have not been previously traumatized in any gross way manifest
      characteristics of trauma.

PMID- 11441516
TI  - Compulsive sexual behavior inventory: a preliminary study of reliability and
      validity.
AB  - This preliminary study was designed to develop empirically a scale of compulsive
      sexual behavior (CSB) and to test its reliability and validity in a sample of
      individuals with nonparaphilic CSB (N = 15), in a sample of pedophiles (N = 35)
      in treatment for sexual offending, and in a sample of normal controls (N = 42).
      Following a factor analysis and a varimax rotation, those items with factor
      loadings on the rotated factors of greater than .60 were retained. Three factors
      were identified, which appeared to measure control, abuse, and violence.
      Cronbach's alphas indicated that the subscales have good reliability. The 28-item
      scale was then tested for validity by a linear discriminant function analysis.
      The scale successfully discriminated the nonparaphilic CSB sample and the
      pedophiles from controls. Further analysis indicated that this scale is a valid
      measure of CSB in that there were significant differences between the three
      groups on the control subscale. Pedophiles scored significantly lower than the
      other two groups on the abuse subscale, with the other two groups not scoring
      significantly differently from one another. This indicated that pedophiles were
      more abusive than the nonparaphilic CSB individuals or the controls. Pedophiles
      scored significantly lower than controls on the violence subscale. Nonparaphilic
      individuals with compulsive sexual behavior scored slightly lower on the violence
      subscale, although not significantly different. As a preliminary study, there are
      several limitations to this study, which should be addressed, in further studies
      with larger sample sizes.

PMID- 11441517
TI  - Gender, sexual dysfunctions, and the Journal of Sex & Marital Therapy.
AB  - The purpose of this study is to examine male and female sexual dysfunctions
      present in the Journal of Sex & Marital Therapy. The Journal of Sex Research, the
      Journal of Sex Education and Therapy, and the Archives of Sexual Behavior also
      are briefly discussed. The types of dysfunctions investigated include female
      orgasmic disorder, female sexual arousal disorder, male erectile disorder, and
      premature ejaculation. The results indicate that the focus has shifted to male
      sexual dysfunctions. Specifically, there is greater attention paid to erectile
      dysfunction. The implications of these findings are discussed.

PMID- 11441518
TI  - Short scale to measure female sexuality: adapted from McCoy Female Sexuality
      Questionnaire.
AB  - This article examines sex-questionnaire data using the Personal Experiences
      Questionnaire (PEQ; Dennerstein, Hopper, & Burger, 1997). We used data from a
      population-based sample of 354 Australian mid-aged women and an optimization
      procedure in order to reduce the length of the PEQ while retaining items
      measuring the components of female sexual functioning and key determinants. Eight
      items were selected. We recommend retaining the item related to orgasm (rejected
      for parsimony only). Eight of the nine items were from the McCoy Female Sexuality
      Questionnaire, confirming the validity of this source scale. The original wording
      in the McCoy scale is recommended as considerable data has now become available
      on reliability and validity.

PMID- 11441519
TI  - Sexual functioning in patients with localized prostate cancer awaiting treatment.
AB  - This article evaluates current sexual functioning in patients with prostate
      cancer who are awaiting treatment. One-hundred fifty-eight patients filled out a
      15-item questionnaire regarding current sexual functioning. Median age was 67
      years. Sixty percent reported to have spontaneous erections at least once a week,
      and 37% reported a good firmness. Thirty-five percent reported that during sexual
      activity they had no difficulty in getting erections, and 33% reported that they
      had no difficulty in maintaining an erection. After diagnosis, all patients
      reported a decrease in sexual interest, activity, and pleasure. Diagnosis of
      prostate cancer does have an impact on sexual functioning, therefore sexual
      counseling prior to treatment is advised.

PMID- 11441520
TI  - Persistent sexual arousal syndrome: a newly discovered pattern of female
      sexuality.
AB  - This article describes a phenomenon, persistent sexual arousal syndrome (PSAS),
      which heretofore has not been noted or described in the sexuality, psychiatric or
      medical literature. The syndrome is precisely the opposite of female sexual
      arousal disorder (FSAD), in that the woman's complaint is of excessive and often
      unremitting arousal rather than of deficient or absent arousal. Five case
      descriptions are reported, highlighting the essential feature of the syndrome-
      persistent physiological arousal in the absence of conscious feelings of sexual
      desire. To date, no obvious hormonal, vascular, neurological, or psychological
      causes have been identified as underlying the symptoms of any of these patients.
      The cases are presented in the hope that they will stimulate efforts to
      investigate the prevalence, etiology, course, and management of PSAS.

PMID- 11441521
TI  - [The role of the selective blocking of angiotensin II receptors in the treatment
      of cardiovascular diseases].
AB  - Angiotensin II plays an important role in blood pressure control and in water and
      salt homeosthasis. It is involved in the pathogenesis of hypertension and
      structural alterations of the vasculature, kidney, and heart, including
      nephrosclerosis, post infarction remodelling and left ventricular hypertrophy. At
      least two subtypes of receptors have been identified, angiotensin type 1 (AT1)
      and type 2 (AT2). The AT1 receptor is responsible for all the known effects of
      Ang II on blood pressure, osmoregulation, and cell growth and consequently for
      the contribution to cardiovascular and renal pathology. Research has indicated
      that the AT1 receptor modulates cardiac and vascular hypertrophy, cellular growth
      and ventricular remodelling. Evidence suggests that, on the other hand, the AT2
      receptor is involved in growth inhibition, inhibits cell proliferation, induces
      vasodilatation and reverses the AT1 induced hypertrophy. The accumulating
      evidence appears to demonstrate therefore that the function of these receptor
      subtypes may exerts opposite effects while stimulated by AngII. The angiotensin
      receptor antagonists are able to inhibit the renin angiotensin system by blocking
      selectively the AT1 receptor. It is supposed that AT1 receptor antagonists may
      provide end organ protection by blocking angiotensin II effects via the AT1
      receptor leaving the AT2 receptor unopposed: it is conceivable that the
      stimulation of AT2 receptors may prevent the hypertropic effects seen in
      conditions such as LVH, hypertrophy, postinfarction remodeling and repair after
      injury. For this, the AT1/AT2 selectivity associated to these drugs may be
      important for their effects and to differentiate them from ACE inhibitors.

PMID- 11441522
TI  - [Imaging of neuroendocrine tumors].
AB  - Neuroendocrine tumors (NET) of the pancreas are distinguished in functional (85%)
      and non functional (15%) in relation to the production and release of the hormone
      produced. Functional tumors show early, because the neoplasm release the hormone
      produced when they are still small. Non functional tumors show late when the
      tumor grows. The localization and the evaluation of the extensive of these tumors
      has come fundamentally important both in correct presurgical detection and also
      in the diagnosis of metastases which excluded surgery. Also, as the survival of
      20% of the patients with metastases is only five years, the use of non-invasive
      imaging techniques is very important for the evaluation of results of the various
      therapies (chemotherapy, interferon, somatostatin). Recent studies have shown
      that in patients with Zollinger-Ellison syndrome, SRS is the most sensitive non
      invasive method in localizing primitive tumors and metastases. The accuracy of
      this technique has not yet been provided in the study of tumors like insulinomas
      which do not have a high percentage of somatostatine receptors on their cell
      membranes. The sensitivity obtained in recent studies on a large number of
      patient and the low cost, lower than all the other imaging technique in use
      today, surely make SRS the first choice in the study of NET. Where SRS is
      negative and surgery is possible, Spiral CT or better still MRI is the best tool
      to check the results of chemotherapy in patients with hepatic metastases (already
      detected by SRS), because it is easier to compare the changes in size and
      morphology of metastases.

PMID- 11441523
TI  - Rabies infection: epidemiology and prophylaxis.
AB  - Authors of this paper underline the importance of worldwide epidemiological
      rabies infection and the prevention. Specifically, a program of health education
      first aid md's, family doctors, veteriners, animal's traders, and to students of
      ground schools (primary and secondary) in a large medical regional area of Rome
      was developed. This article is informative to whom can concern rabies infection
      risks in Italy in order to reduce the abuse of vaccination influencing on
      behaviors and on the relation humans-animals.

PMID- 11441524
TI  - [Development of cancer chemotherapy. Cytoprotective agents].

PMID- 11441525
TI  - "TpP": a new marker in the early diagnosis of acute thrombotic and embolic
      diseases.

PMID- 11441526
TI  - [Therapeutic perspectives: association of ACE inhibitors and angiotensin receptor
      blockers].

PMID- 11441527
TI  - [Is carbamazepine a new etiologic factor in algodystrophy?].

PMID- 11441528
TI  - [Technique and humanization in invasive cardiology].
AB  - The technique used in invasive cardiology, in special way in the PTCA, is here
      considered technique of first and second order (Donati's classification). This
      kind of technique is a chance to improve the physician-nurse relationship with
      patient and the knowledge of the patient on his/her own body. We must use this
      technique in order to get better the relation with the patient trough an
      excellent information during all the procedure.

PMID- 11441529
TI  - [Determination of the blood ascorbic acid level after administration of slow
      release vitamin C].
AB  - PURPOSE: The aim of the present study was to test the effects of a slow releasing
      form of vitamin C in smokers, because the single high dose previously proposed
      for smokers gave a transient increase of plasma ascorbate, being rapidly absorbed
      in the gastrointestinal tract and is rapidly excreted with urine. MATERIALS AND
      METHODS: In a double-blind placebo-controlled study 18 subjects received both
      Vitamin C (C-test) and placebo (P-test) in two different periods. During the test
      day the subject followed a controlled diet and food Intake was assessed by
      semiquantitative questionnaire. Peripheral blood sample were collected in fasting
      conditions, in the morning, before and after 4, 8, 12 and 24 hours from the
      treatment. Blood sample was collected into EDTA-containing tubes, immediately
      centrifuged and treated for ascorbate determination, and stored at -70 degrees C
      until chromatographic analysis. RESULTS: Smokers and nonsmokers were similar for
      age, height, weight, BMI and for vegetable and fruit consumption. Ascorbic acid
      level was significantly (p < 0.05) lower than the references level in all
      subjects, however there were no differences between smokers and non smokers
      plasma ascorbate concentration increased significantly at T1, T2 and T3 respect
      to T0 during C test (p < 0.005), whenever remaining higher than T0 was not still
      significant in T4. CONCLUSION: Our results demonstrate that a slow releasing form
      of Vitamin C could be useful in clinical pharmacology to increase and to maintain
      to a constant rate ascorbate level, both in smokers and non smokers with a single
      daily administration.

PMID- 11441530
TI  - [Argyrophilic nucleolar organizer regions (AgNORs) as malignancy biomarkers in
      colorectal neoplasms].
AB  - The high incidence of intestinal cancer has aroused strong interest in
      researching and trying to discover its morphologic precursors. In this contest
      the study of nucleolar organizing regions could be interesting as prognostic
      factor for bowel neoplasm and useful for differential diagnosis of intestinal
      diseases. The Authors report on the results of their study performed on 30
      selected samples from 6 different bowel lesions.

PMID- 11441531
TI  - [Individualization of the "presumptive risk" of hypertensive crisis using
      fractals interpolation of the 24-hour arterial pressure. Study of patients with
      essential hypertension].
AB  - PURPOSE: The present study applies the "fractal interpolation" (FI) to blood
      pressure that was nonivasively and ambulatorily monitored over a day-night period
      in essential hypertensives. The purpose is the identification of cases who are at
      a "presumptive risk" (PR) for hypertensive crisis. MATERIALS AND METHODS: The
      investigation was performed on 380 ascertained cases of essential hypertension,
      who underwent a non-invasive ambulatory monitoring of 24-h blood pressure. The FI
      was applied to the ambulatory mean arterial pressure. RESULTS: The FI showed that
      the PR of hypertensive crisis can be found in 14% of the investigated essential
      hypertensive patients. Such a risk is not significantly higher in dippers as
      compared to non-dippers, and in those who showed a significant blood pressure
      circadian rhythm as compared to those who showed the blood pressure circadian
      rhythm to be abolished. Furthermore, no significant difference was found between
      the cases "at risk" and "not at risk" as far as the spectrum of harmonic formants
      of the 24-h blood pressure pattern is concerned. CONCLUSIONS: The PR of
      hypertensive crisis is not correlated to the dipping/nondipping condition,
      circadian rhythmicity and complex harmonic structure of 24-h blood pressure
      pattern. Its occurrence depends essentially from the disorder that is detectable
      in 24-h blood pressure pattern. Therefore, such a PR in essential hypertensives
      may be attributed to the mechanisms, likely neurovegetative, which confer a non
      linear chaotic variability to 24-h blood pressure values.

PMID- 11441532
TI  - Generation of p53 suppressor peptide from the fragment of p53 protein.
AB  - The p53 protein, encoded by a tumor suppressor gene, mediates growth arrest or
      apoptosis in response to a variety of stresses. p53-dependent apoptosis,
      occurring in several sensitive tissues after radiation or chemotherapy, is
      partially responsible for the side effects of cancer treatment, making p53 a
      potential target for therapeutic suppression. p53 function can be suppressed by
      the ectopic expression of p53-derived peptides, isolated earlier using functional
      selection of genetic suppressor elements (GSEs) from a library of randomly
      fragmented p53 cDNA (Ossovskaya et al. [1996]. Proc. Natl. Acad. Sci. U.S.A. 93,
      10309). The potent p53-suppressing GSE, GSE56, had been used to generate in an E.
      coli expression system a peptide with anti-p53 activity by fusion of the GSE
      encoded sequence with penetratin, a 16-amino-acid-long peptide capable of
      efficient translocation through cell membranes. Fusion with penetratin does not
      affect the anti-p53 activity of retrovirus-transduced GSE56. The fused peptide
      was able to attenuate p53-mediated transactivation and apoptosis when added into
      culture media. Interestingly, GSE56-derived peptide with no penetratin also had
      accumulated in the cells and showed similar, though lower, anti-p53 activity.
      This study provides the rationale and methodological basis for efficient
      generation of biologically active peptides with therapeutic potential from GSEs
      isolated through functional selection.

PMID- 11441533
TI  - On the spontaneous mutability of CpG sites in cultured S49 mouse lymphoma cells.
AB  - The frequent occurrence of human mutations at CpG dinucleotide sites has been
      attributed to cytosine methylation and hydrolytic deamination of the resulting 5
      methylcytosine residue. Previously, we reported an unusually strong hotspot for
      spontaneous transitions at a CpG site in the gene for regulatory (R) subunit of
      protein kinase A in S49 mouse lymphoma cells. Now, using polymerase chain
      reaction-based methods to screen mutant populations for mutations at particular
      CpG sites, we show that two methylated CpG sites in the gene for hypoxanthine
      phosphoribosyltransferase are much less mutable than the R subunit hotspot site,
      suggesting that different methylated CpG sites are differentially susceptible to
      spontaneous mutation. We also present data on spontaneous R subunit mutations in
      cloned populations of 5-azacytidine-treated S49 cells that had been demethylated
      at the hotspot site in both R subunit alleles. Of 13 independent mutants isolated
      from populations grown from fully demethylated cells, seven had the hotspot
      mutation. We conclude that CG-->TA mutations at strong CpG hotspots do not
      require prior methylation of CpG sites.

PMID- 11441534
TI  - Antigen S1, encoded by the MIC1 gene, is characterized as an epitope of human
      CD59, enabling measurement of mutagen-induced intragenic deletions in the AL cell
      system.
AB  - S1 cell membrane antigen is encoded by the MIC1 gene on human chromosome 11. This
      antigen has been widely used as a marker for studies in gene mapping or in
      analysis of mutagen-induced gene deletions/mutations, which utilized the human
      hamster hybrid cell-line, AL-J1, carrying human chromosome 11. Evidence is
      presented here which identifies S1 as an epitope of CD59, a cell membrane
      complement inhibiting protein. E7.1 monoclonal antibody, specific for the S1
      determinant, was found to react strongly with membrane CD59 in Western blotting,
      and to bind to purified, urinary form of CD59 in ELISAs. Cell membrane expression
      of S1 on various cell lines always correlated with that of CD59 when examined by
      immunofluorescent staining. In addition, E7.1 antibody inhibited the complement
      regulatory function of CD59. Identification of S1 protein as CD59 has increased
      the scope of the AL cell system by enabling analysis of intragenic mutations, and
      multiplex PCR analysis of mutated cells is described, showing variable loss of
      CD59 exons.

PMID- 11441535
TI  - Cloning and characterization of Chinese hamster CDC7 (ChCDC7).
AB  - The Cdc7 serine/threonine kinase is essential for entry into and to traverse
      through S phase. We have cloned the putative Chinese hamster CDC7 (ChCDC7) cDNA
      that is capable of encoding a protein of 572 amino acids with predicted molecular
      mass of 62.6 kDa. The ChCdc7 protein includes all 11 kinase domains that are
      conserved among the Cdc7-related protein kinases. In addition, the ChCdc7 protein
      kinase contains at least two kinase inserts that show substantial identity to
      those of huCdc7p. Overall, ChCdc7p shares 81, 56, 30, and 27% amino acid sequence
      identity with the Cdc7-related proteins of human, Xenopus, Saccharomyces
      cerevisiae, and Schizosaccharomyces pombe, respectively. Although the levels of
      ChCDC7 mRNA and protein are relatively constant throughout the cell cycle in the
      cycling cells, they are extremely low in the cells synchronized in the quiescent
      stage (i.e., G0). When cells in G0 are released into the cell cycle, the levels
      of ChCDC7 mRNA and protein increase slowly until the cells reach the G1/S border,
      at which time the increase is rapid. This suggests that a number of signal
      transduction pathways may have to be activated prior to CDC7 gene expression.
      Interestingly, the ChCdc7-GFP fusion protein formed discrete granules in the
      nuclei of cells arrested in early S phase by aphidicolin, raising the possibility
      that ChCdc7p is part of the "replication factory."

PMID- 11441536
TI  - Allocyclic X chromosome visualized by drug-induced premature chromosome
      condensation.
AB  - Calyculin A, an inhibitor of serine/threonine protein phosphatases, can induce
      premature chromosome condensation (PCC) in human peripheral lymphocytes. In
      female lymphocytes treated with calyculin, one highly condensed chromosome per
      nucleus was frequently observed at early to middle S phase. When these PCC
      spreads were hybridized with a whole chromosome-painting probe for the X
      chromosome, one large spot and a cluster of small spots were observed in a cell.
      Judging from the Giemsa stained image, the former seemed to have finished DNA
      replication, while the latter was in the process of replication. Because this
      large spot was seldom observed in male PCC spreads, it was considered an inactive
      X chromosome. The inconsistency of this observation with earlier reports that the
      inactive X chromosome replicates later than autosomes and the active homolog is
      discussed.

PMID- 11441537
TI  - cDNA sequence and mapping of the mouse Copb gene encoding the beta subunit of the
      COPI coatomer complex.
AB  - COPI-coated vesicles are involved in retrograde-directed selective transport of
      proteins from the Golgi complex to the endoplasmic reticulum (ER) as well as
      mediate anterograde transport of cargo proteins within the Golgi or in endosomal
      trafficking. The COPI protein complex contains an ADP-ribosylation factor (ARF1)
      and seven coatamer subunits (alpha, beta, beta', gamma, delta, epsilon, zeta
      COP). The localization and function of human beta subunit of coatamer (COPB)
      suggests it is likely a candidate gene of ruby-eye-2 (ru2), which is a mouse
      model of human Hermansky-Pudlak syndrome characterized by the dysfunction of
      several subcellular organelles. In this study, we determined the entire coding
      sequence of mouse (Copb) cDNA by combining an overlapping mouse EST contig with
      EST walking. beta-COP was found highly conserved in mouse, rat, and human, and it
      is ubiquitously expressed in mouse. The Copb gene was mapped to mouse Chr 7 at a
      position of 53.3 cM by radiation hybrid mapping. Our RH mapping data, sequencing
      of RT-PCR products, and Western blotting exclude the Copb gene as a candidate for
      ru2.

PMID- 11441538
TI  - Genomics of the human genes encoding four TAFII subunits of TFIID, the three
      subunits of TFIIA, as well as CDK8 and SURB7.
AB  - By in situ chromosomal hybridization, and by somatic cell and radiation hybrid
      analysis, we have determined the genomic position of the human genes encoding
      four TAFII subunits of TFIID (TAFII150, TAFII105, TAFII68, TAFII18), the three
      subunits of TFIIA (TFIIA35 and TFIIA19, both encoded by the same gene, and
      TFIIA12), CDK8, and SURB7. All of these proteins are bona fide components of
      human class II holoenzymes as well as targets of signal transduction pathways
      that regulate genome expression. The genes encoding them are present in the human
      genome in a single copy and are localized at 8q23, 18q11.2, 17q11.1-11.2, 1p21,
      14q31, 15q21-23, 13q12, and 12p12, respectively. We have mapped all of them to
      chromosomal regions where hereditary genetic diseases have been localized or
      which are involved in malignancies, which makes them potential candidates for a
      causal involvement in these phenotypes.

PMID- 11441539
TI  - Effects of implant design and surface on bone regeneration and implant stability:
      an experimental study in the dog mandible.
AB  - BACKGROUND: Previous experimental studies have shown a higher degree of bone
      implant contact for surface-enlarged implants compared with machined implants.
      Yet, there is insufficient evidence that such implants show higher stability and
      an increased survival rate. PURPOSE: The purpose of this investigation was to
      study the integration and stability of grit-blasted implants with retention
      elements on the implant neck, with and without marginal bone defects, compared
      with machined implants without retention elements. MATERIALS AND METHODS: After
      tooth extraction of the mandibular premolars in six dogs, two grit-blasted,
      partly microthreaded Astra Tech implants and one standard Branemark implant were
      bilaterally placed in each dog. On one side, 3 x 3 mm large buccal defects were
      created, to expose three to four implant threads. The contralateral side served
      as control, and no defects were made. The animals were sacrificed after 4 months
      of healing. Implant stability was measured using resonance frequency analysis at
      implant installation and after 4 months of healing. Histologic and
      histomorphometric evaluation was made after 4 months of healing. RESULTS:
      Resonance frequency analysis indicated that all implants in the test and control
      groups were osseointegrated after 4 months, with a tendency toward higher implant
      stability for the Astra Tech implants. There was a statistically significant
      higher increase in resonance frequency for the Astra test implants compared with
      their corresponding controls. Histology and histomorphometry showed well
      integrated implants with varying degrees of bone repair at the defect sites. The
      greater bone-implant contact for the Astra implants was statistically
      significant. No significant difference between the implants in amount of bone
      filling the threads was recorded. CONCLUSIONS: The Astra Tech implants tested
      showed a higher degree of bone-implant contact and higher level of bone
      regenerated at defect sites compared with the Branemark implants. Resonance
      frequency analysis demonstrated a significantly higher increase in the Astra test
      implants compared with their control groups than did the Branemark test implants
      versus their controls.

PMID- 11441540
TI  - Nonsubmerged implants in the treatment of the edentulous lower jaw: a 5-year
      prospective longitudinal study of ITI hollow screws.
AB  - BACKGROUND: Although most implant systems have been designed for a two-stage
      surgical technique, a one-stage surgical technique has always been advocated for
      the ITI Dental Implant System (Straumann AG, Waldenburg, Switzerland). A new
      generation of ITI implants was presented in 1988 and included a hollow cylinder,
      a hollow screw, and a solid screw. PURPOSE: The goal of this study was to
      evaluate the one-stage surgical technique in connection with the ITI hollow screw
      in a longitudinal study over 5 years. MATERIALS AND METHODS: Forty-six patients
      with edentulous lower jaws were supplied with ITI hollow-screw implants. Patients
      who requested an overdenture (n = 18) had four implants inserted; those who
      requested a fixed bridge (n = 28) had five to six implants. The patients have
      been followed annually for 5 years. There was a dropout of three patients (6.5%);
      one patient did not want to cooperate, one moved from the area, and one was
      deceased. The clinical examinations included bridge removal for evaluation of the
      individual implant stability in connection with the 1-, 3-, and 5-year
      examinations. Radiographic examinations were performed with intraoral radiographs
      and the long-cone technique. RESULTS: The survival rate after 5 years was 95.7%.
      The success rate (in which implants undergoing treatment of peri-implantitis were
      not counted as successes) was 91.4%. The mean marginal bone loss between the
      baseline and the 1-year examination was 0.1 mm and between the 1- and 5-year
      examinations was 0.1 mm. These changes in marginal bone level were not
      significant. CONCLUSIONS: The success rate of ITI hollow-screw implants in the
      edentulous mandible was 91.4% after a 5-year observation period. There was no
      significant change in mean bone level between the loading of the implants and the
      5-year examination. Peri-implantitis was diagnosed in three patients with poor
      oral hygiene, and it affected six implants. Five of these failed in spite of
      treatment.

PMID- 11441541
TI  - Evaluation of factors influencing the marginal bone stability around implants in
      the treatment of partial edentulism.
AB  - BACKGROUND: The original protocol of Branemark to achieve predictable
      osseointegration for oral implants has substantially been modified. One may
      question whether results are influenced by those modifications, especially for
      the long-term prognosis. PURPOSE: The goal of the present study was to
      investigate the impact of those parameters that deviate from the original
      protocol as defined by P-I Branemark. MATERIALS AND METHODS: In this study, 246
      patients with 263 fixed partial prostheses supported by 668 Branemark implants
      were followed from 1 to 15 years (mean: 6.3 yr). Radiographs were taken at the
      time of abutment connection, at 3 to 6 months, at 12 months, and then every 3
      years. The bone level was rated mesially and distally from the implants on a
      total of 2588 radiographs. RESULTS: A positive relation between abutment length
      and marginal bone level was found (p > .0001). The maxilla (p = .03), porcelain
      (p = .007), long abutments (p = .008), and regular-sized diameter implants (p =
      .001) all exhibited more bone loss in the first 6 months. After 6 months, only
      long implants showed more bone loss (p = .03). CONCLUSIONS: Overall, the marginal
      bone level remained stable around Branemark implants, never surpassing 2.2 mm,
      even after 15 years. Although longer implants lost more bone over time, this has
      to be interpreted with respect to higher resorption rates in less resorbed jaws.

PMID- 11441542
TI  - Tilted implants as an alternative to maxillary sinus grafting: a clinical,
      radiologic, and periotest study.
AB  - BACKGROUND: Owing to mechanical and anatomic difficulties, implant treatment in
      the atrophic maxilla represents a challenge. The maxillary sinus floor
      augmentation procedure is still not universally accepted because of its
      complexity and its unpredictability. PURPOSE: In this study, a combination of
      tilted and axial implants was used in patients with severely resorbed posterior
      maxillae as an alternative to sinus grafting. MATERIALS AND METHODS: Twenty-five
      patients were rehabilitated with 29 fixed partial prostheses supported by 101
      Branemark System implants. Fifty-nine implants were installed in an axial and 42
      in a tilted direction. The average follow-up period was 37 months (range: 21-87
      mo post loading). RESULTS: After 5 years, the implant cumulative success rate was
      95.2% (survival: rate 100%) for the tilted implants and 91.3% (survival rate:
      96.5%) for the axial implants, and the prosthesis survival rate was 100%. At the
      fifth year, the average marginal bone loss was 1.21 mm for the tilted implants
      and 0.92 mm for the axial ones. The mean Periotest values (PTV) at loading time
      were -2.62 and -3.57, and after 5 years the PTVs were -4.73 and -5.00 for the
      tilted and the axial implants, respectively. During the follow-up, all prostheses
      but two were mechanically stable, retightening of 18 abutment screws and of 5
      gold screws in 14 prostheses was done, and fracture of two abutment screws and
      two occlusal surfaces was experienced. CONCLUSIONS: Results indicate that the use
      of tilted implants is an effective and safe alternative to maxillary sinus floor
      augmentation procedures.

PMID- 11441543
TI  - Branemark implants and osteoporosis: a clinical exploratory study.
AB  - BACKGROUND: Oral implant treatment on patients with poor jaw-bone texture has
      shown increased failure rates in series of studies. PURPOSE: The purpose of the
      present study was to retrospectively follow patients with osteoporosis of the
      axial or appendicular skeleton, including the jaw bone, being subjected to oral
      implant treatment. The outcome of inserted implants, when using an adapted bone
      site preparation technique and extended healing periods, was evaluated. MATERIALS
      AND METHODS: Based on data obtained from preoperative radiographs, patient
      medical history, and resistance of the jaw bone perceived during drilling, 14 of
      16 patients were referred to the Osteoporosis Laboratory, Sahlgren University
      Hospital, Goteborg, Sweden, for bone density measurements. Two patients already
      had an established diagnosis of osteoporosis. Fourteen jaws in 13 patients (11
      females, 2 males; mean age: 68 yr) were subsequently subjected to oral implant
      treatment with a total of 70 implants (Branemark System) of various designs. The
      mean follow-up period was 3 years and 4 months (range: 6 mo-11 yr). RESULTS:
      Osteoporosis of either the spine, the hip, or both regions was diagnosed in 14
      patients, and osteopenia was diagnosed in 2 patients. Two implants failed, and
      the overall implant survival rate at the end of the study period was 97.0% for
      maxillae and 97.3% for mandibles. The marginal bone resorption at the 1-year
      follow-up concurs with the outcome of other studies, irrespective of the
      preoperative bone texture present. CONCLUSION: The outcome of the present study
      showed that implant placement in patients in whom the average bone density showed
      osteoporosis in both lumbar spine and hip as well as poor local bone texture may
      be successful over a period of many years.

PMID- 11441544
TI  - Nonresorbable versus resorbable sutures in oral implant surgery: a prospective
      clinical study.
AB  - BACKGROUND: Regarding the Branemark implant system, nonresorbable sutures have
      been advocated for reapproximation of the flaps. Fast-absorbable sutures are
      frequently used in oral surgery, which is convenient for both the patient and the
      surgeon. It would be advantageous if fast-absorbable sutures are suitable in
      implant surgery as well. PURPOSE: The purpose of this study was to compare
      irradiated polyglactin 910 (Vicryl Rapide, Ethicon GmbH, Norderstedt, Germany)
      suture with a nonresorbable polyfilament suture (Supramid, Schwarz, Resorba GmbH,
      Nurnberg, Germany) used in oral implant surgery. MATERIALS AND METHODS: The study
      comprised 101 edentulous patients (52 females, 49 males) who were provided with
      350 Branemark implants. They were randomized to receive either Vicryl Rapide
      suture (n = 61) or 3-0 Supramid suture (n = 40). The patients were evaluated
      after 10 days and at the time of abutment surgery. Any wound complications and
      implant losses were recorded. RESULTS: The implant failure rate at abutment
      surgery was low (1.2%), and no difference was seen between the two suture groups.
      A higher incidence of complications (mainly wound dehiscence) was found in the
      absorbable suture group, especially when a continuous suture was used.
      CONCLUSIONS: The results of this study indicate that it is possible to use
      irradiated polyglactin 910 sutures in oral implant surgery without affecting the
      rate of early implant failure. However, it is recommended to add interrupted
      "security sutures" if a continuous suture technique is used in combination with
      fast-absorption suture material.

PMID- 11441545
TI  - One-year prospective evaluation of the early loading of unsplinted conical
      Branemark fixtures with mandibular overdentures immediately following surgery.
AB  - BACKGROUND: Prospective evaluation of the early loading of unsplinted Branemark
      implants with mandibular overdentures opposing conventional dentures is not
      evident in the implant-related literature. PURPOSE: To clinically evaluate
      progressive and early loading of 20 unsplinted conical Branemark implants in
      edentulous mandibles with overdentures. MATERIALS AND METHODS: Ten edentulous
      patients all had two conical Branemark implants placed in the anterior mandible
      with mandatory primary stability with bicortical anchorage. Ball abutment
      connection was performed simultaneously. Previously constructed conventional
      mandibular dentures were temporarily relined with tissue conditioner
      postoperatively and worn with moderation for the first 2 weeks to allow
      progressive loading. Early loading of the implants followed after 2 weeks, with
      inclusion of the respective matrices in the mandibular dentures, using a
      definitive reline procedure. RESULTS: All patients successfully functioned with
      their mandibular implant overdentures from 2 to 52 weeks postoperatively. Mean
      marginal bone loss was within established criteria for success: 0.22 mm (SD =
      0.48 mm) mesially and 0.30 mm (SD = 0.39 mm) distally on the conical implants.
      Mobility tests using the Periotest instrument became more negative, although not
      at statistically significant levels. Difficulties in the management of the peri
      implant mucosa between surgery and loading at 2 weeks were observed in 40% of the
      patients. CONCLUSIONS: These preliminary 1-year results show that successful
      early loading of unsplinted conical Branemark implants with mandibular
      overdentures is possible.

PMID- 11441546
TI  - Percutaneous radiofrequency thermal ablation of liver malignancies: techniques,
      indications, imaging findings, and clinical results.

PMID- 11441547
TI  - Thermal ablation of liver metastases.

PMID- 11441548
TI  - Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases.
AB  - BACKGROUND: Many primary tumors may cause liver metastases, which are generally
      treated with surgical resection and/or chemotherapy. After resection of liver
      metastases in patients with colorectal carcinoma, 5-year survival rates are
      achieved in 25-38%, and two-thirds of patients will experience recurrent
      metastases. We examined percutaneous, minimally invasive, laser-induced
      thermotherapy (LITT) as an alternative outpatient procedure. Local tumor control
      rate and survival data were analyzed prospectively. METHODS: Between June 1993
      and August 2000, 7148 laser applications were performed in 1981 lesions in 705
      consecutive patients and 1653 treatment sessions. The complications of the
      procedure were evaluated by clinical examination and magnetic resonance imaging
      (MRI) and computed tomography. Local tumor control was evaluated by plain and
      contrast-enhanced follow-up MRI using T1- and T2-weighted spin-echo and gradient
      echo sequences every 3 months after treatment. Cumulative survival times were
      calculated using the Kaplan-Meier method. RESULTS: The overall rate of
      complications and side effects was 7.5%. The rate of clinically relevant
      complications was 1.3%. Local tumor control rate after 3 months was 99.3%; 6
      months after laser treatment, plain and contrast-enhanced MRI documented a local
      tumor control rate of 97.9%. In patients treated with MR-guided LITT for
      unresectable colorectal liver metastases, the mean survival was 41.8 months (95%
      confidence interval = 37.3-46.4 months). The 1-year survival rate was 93%, the 2
      year survival rate was 74%, the 3-year survival rate was 50%, and the 5-year
      survival was 30%. In patients treated with LITT for liver metastases from breast
      cancer, the mean survival was 4.3 years (95% confidence interval = 3.6-5.0
      years). CONCLUSION: In patients with liver metastases, local tumor destruction
      using minimally invasive, percutaneous LITT under local anesthesia results in
      improved clinical outcomes and survival rates and can be a potential alternative
      to surgical resection.

PMID- 11441549
TI  - Hepatocellular carcinoma recurrence after percutaneous ablation therapy: helical
      CT patterns.
AB  - BACKGROUND: To categorize the helical computed tomographic (CT) intrahepatic
      recurrence patterns of hepatocellular carcinoma (HCC) after treatment with
      percutaneous ablation procedures. METHODS: Double-phase helical CT studies of 67
      patients with HCC recurrence were reviewed. The study population had undergone
      percutaneous ablation therapy procedures (multisession or single-session ethanol
      injection therapy, radiofrequency thermal ablation therapy, and interstitial
      laser photocoagulation therapy) for 120 HCC nodules. RESULTS: Four patterns were
      defined. (A) Enhancing tissue within the edge of the ablated nodule on arterial
      phase images (ingrowth): this pattern was seen in five treated lesions (4.2% of
      all treated nodules) in five patients (7.5% of all patients with recurrence) 3-7
      months after treatment (mean = 4 months). (B) Enhancing tissue around the treated
      nodule but continuously to its border on arterial-phase images (outgrowth): this
      pattern was found in 12 (10%) treated lesions in 12 patients (18%) 3-6 months
      after ablation (mean = 4 months). (C) Enhancing tissue within the same segment of
      the treated nodule on arterial phase images (spread): this pattern was detected
      in 10 (8%) treated lesions in 10 patients (15%) 3-6 months after treatment (mean
      = 5 months). (D) Enhancing tissue within different segments from the treated
      nodule on arterial phase images (progression): this pattern was identified in 34
      patients (51%) with 53 (44%) treated tumors 5-22 months after ablation (mean = 8
      months). A mixed pattern was found in six subjects (9%) with seven (6%) treated
      nodules. Among the 61 patients with a nonmixed pattern, there were 85 treated
      nodules with persistent necrosis, 17 treated nodules with local recurrence
      (pattern A or B), and 107 new nodules due to nonlocal recurrence (pattern C or
      D). Portal phase enhanced images and especially unenhanced images showed a lower
      detection rate and a lower lesion-to-liver conspicuity score (for all patterns
      but mainly for pattern C). CONCLUSION: Four patterns of recurrence after
      percutaneous ablation procedures can be categorized on double-phase helical CT
      and are best depicted on arterial phase images. Knowledge of these patterns is
      relevant for early detection and may be helpful in understanding the recurrence
      mechanism.

PMID- 11441550
TI  - Peritumoral spared area in fatty liver: correlation between opposed-phase
      gradient-echo MR imaging and CT arteriography.
AB  - BACKGROUND: The purpose of the present study was to evaluate the magnetic
      resonance findings of a spared area of fatty liver caused by hepatic tumors and
      clarify the etiology of this phenomenon by computed tomographic (CT)
      arteriography. METHODS: Six patients with hepatic tumors (metastases from colon
      cancer, n = 3; breast cancer, n = 2; hepatocellular carcinoma, n = 1) were
      examined. In-phase (IP) and opposed-phase (OP) T1-weighted spoiled gradient-echo
      images were obtained. CT during arterial portography (CTAP) and CT during hepatic
      arteriography (CTHA) were also performed. Pathologic confirmation was obtained in
      three patients with metastases from colon cancer. RESULTS: In all six patients,
      peritumoral ringlike or wedge-shaped hyperintense areas in relation to the tumor
      and the surrounding steatotic liver parenchyma were clearly visualized on OP
      images alone. This area appeared as a perfusion defect on CTAP and ringlike or
      wedge-shaped enhancement on CTHA. Pathologically, the peritumoral hyperintense
      areas on OP images were compatible with the spared area of fatty liver.
      CONCLUSION: A peritumoral spared area can be demonstrated with OP images. The
      etiology of the phenomenon is correlated with decreased portal flow and increased
      arterial flow in the peritumoral hepatic parenchyma.

PMID- 11441551
TI  - Portal venous gas: detection by gray-scale and Doppler sonography in the absence
      of correlative findings on computed tomography.
AB  - Two cases are described in which portal venous gas (PVG) was detectable by
      ultrasound, but the liver appeared normal on computed tomography (CT). The
      finding of PVG was associated with ischemic bowel in one case but was a benign
      finding in the other case. The gray-scale and Doppler ultrasound findings
      associated with PVG are described. This case report illustrates two key points.
      First, ultrasound may detect gas within the portal venous system when CT is
      negative. Second, when PVG is detected on ultrasound, urgent clinical assessment
      followed by contrast-enhanced CT is indicated to assess for associated intestinal
      ischemia.

PMID- 11441552
TI  - Choledochal cyst due to anomalous pancreatobiliary junction in the adult:
      sonographic findings.
AB  - BACKGROUND: Adult cases of choledochal cyst due to anomalous pancreaticobiliary
      duct junction have been rarely reported. At present, sonography (US) is the first
      tool for diagnosing biliary disorders. The aim of this study was to reevaluate
      the US findings of choledochal cysts due to anomalous pancreaticobiliary duct
      junction in adults. METHODS: We reviewed the clinical manifestations and US
      findings of 12 such adult cases confirmed by endoscopic retrograde
      cholangiopancreatic ductography (ERCP). Patients were assigned to three groups:
      (a) associated with biliary carcinoma (two cases), (b) associated with
      choledocholithiasis (one case), and (c) not associated with other abdominal
      diseases (nine cases). RESULTS: Patients in group c were asymptomatic, and the
      lesions were detected incidentally detected by US. In contrast, patients in group
      a sought medical care because of symptoms such as jaundice and those in group b
      sought medical attention because of abdominal pain. The diameter of a dilated
      bile duct on US was considerably less than that of ERCP (ERCP: 26-58 mm, mean =
      37.6 mm; US: 13-32 mm, mean = 21.8 mm). Its diameter changed significantly under
      probe compression when the dilated bile duct took a purely cystic form but
      changed very little when it took a tubular form. CONCLUSION: Unlike cases in
      children, adult cases of choledochal cyst are generally asymptomatic. Careful US
      observation of the bile duct is thus expected to detect asymptomatic adult
      choledochal cysts cases. Cyst diameter can change significantly under probe
      compression, so it is important not to compress the bile duct during routine US
      examination.

PMID- 11441553
TI  - Gallstone ileus: increased diagnostic sensitivity by combining plain film and
      ultrasound.
AB  - BACKGROUND: Gallstone ileus is an uncommon cause of mechanical obstruction. Its
      high mortality rate can be reduced with earlier diagnosis and treatment. We
      wanted to determine whether ultrasound (US) performed after plain film increases
      the sensitivity for the preoperative diagnosis. METHODS: We performed a 5-year
      retrospective analysis of radiologic and sonographic results of 23 patients who
      had surgery because of gallstone ileus. RESULTS: Rigler's triad was identified by
      plain abdominal film in two patients (9%) and by US in 16 patients (69%). Plain
      abdominal film contributed to a definitive diagnosis in four cases and to a
      probable diagnosis in six cases (sensitivities of 17% for definitive diagnoses
      and 43% for definitive and probable diagnoses). US confirmed the diagnosis in six
      cases of probable gallstone ileus and provided the diagnosis in seven of 13
      patients without suspected gallstone ileus based on plain abdominal film. The
      best results were obtained by combining plain film and US findings, with
      sensitivities of 74% for definitive diagnoses and 96% for definitive plus
      probable diagnoses. CONCLUSION: The preoperative diagnosis of gallstone ileus
      significantly increases by combining plain film and US findings.

PMID- 11441554
TI  - CT appearance of disseminated peritoneal adenomucinosis.
AB  - Disseminated peritoneal adenomucinosis (DPAM) is a relatively rare cause of
      pseudomyxoma peritonei, marked by peritoneal lesions with abundant extracellular
      mucin and little cytologic atypia among exfoliated tumor cells, and usually
      associated with appendiceal adenomas. Peritoneal mucinous carcinomatosis (PMCA)
      also causes diffuse peritoneal tumor but is marked by neoplastic mucinous
      epithelium with cytologic features of carcinoma and associated with appendiceal,
      colon, gastric, or small bowel carcinoma. Compared with PMCA, DPAM has a
      different distribution of disease and a significantly better prognosis. DPAM is
      characterized by the lack of lymph node involvement, with primarily superficial
      peritoneal involvement, and a relatively benign, relapsing course over many
      years. Dominant primary masses may not be evident in DPAM. Despite considerable
      overlap in the two main causes of pseudomyxoma peritonei, there are features of
      the two that may help differentiate between them. We present the computed
      tomographic appearance of DPAM in a series of seven cases and emphasize
      characteristics of the disease.

PMID- 11441555
TI  - Acute mesenteric and retroperitoneal lymphadenitis in systemic lupus
      erythematosus: case report.
AB  - In a young woman with clinical evidence of acute cutaneous, musculoskeletal, and
      neurologic manifestations of systemic lupus erythematosus, computed tomography
      (CT) showed enlarged, centrally hypoattenuating mesenteric and retroperitoneal
      lymph nodes. After treatment with steroids, the CT appearance of the lymph nodes
      returned to normal. The differential diagnosis of lymph nodes with central
      hypoattenuation includes Mycobacterium tuberculosis infection, metastatic disease
      (especially squamous cell carcinoma and germ cell tumor), Whipple's disease, and
      celiac disease in addition to lupus lymphadenitis.

PMID- 11441556
TI  - Widespread abdominal venous thrombosis in paroxysmal nocturnal hemoglobinuria
      diagnosed on CT.
AB  - Paroxysmal nocturnal hemoglobinuria is a rare disorder characterized by
      pancytopenia. One of the main manifestations of this disease is development of
      widespread life-threatening venous thrombosis, which may involve multiple
      abdominal veins. We describe two patients with paroxysmal nocturnal
      hemoglobinuria with clinically unsuspected portal, splenic, and mesenteric venous
      thromboses that were diagnosed on computed tomography. This complication should
      be clinically suspected in patients suffering from paroxysmal nocturnal
      hemoglobinuria who present with abdominal pain, and it should be sought by the
      radiologist on pre- and postcontrast computed tomography.

PMID- 11441557
TI  - Mycotic abdominal aneurysm: report of a case with emphasis on the presence of gas
      echoes.
AB  - Mycotic abdominal aneurysm is a relatively rare disease and its sonographic (US)
      findings have rarely been reported. We present a case of mycotic aneurysm of the
      common iliac artery in which the initial US showed a slightly wall-thickened
      abdominal aorta with gas echoes in the wall, a second US 6 days later showed a
      rapid increase in aortic size, and an emergent surgical intervention showed a
      mycotic aneurysm. This interesting observation suggested that the presence of gas
      echoes is a useful US finding indicating the beginning of a mycotic aneurysm and,
      when encountering this US finding, that emergent treatment should be considered
      to prevent delay in patient management.

PMID- 11441558
TI  - Prostatic abscess in young males: a rare complication of Crohn's disease.
AB  - We report a rare case of prostatic abscess with Crohn's disease in a 21-year-old
      male. Computed tomography showed a typical prostatic abscess. Moreover, filling
      of the abscess cavities with contrast medium was demonstrated after micturition,
      which represented the rupturing of the abscess into the urethra. Crohn's disease
      should be included in the differential diagnosis of prostatic abscesses even in
      young males.

PMID- 11441559
TI  - High-resolution ultrasound in the evaluation of the nonacute testis.
AB  - Ultrasound is the initial imaging modality used in the evaluation of the
      symptomatic testis. Ultrasound is painless and quick and supplements clinical
      examination of the testis. In this review, a range of testicular pathologies are
      discussed and sonographic examples illustrated. Particular attention is drawn to
      testicular microlithiasis and its relation to germ cell neoplasia and also to the
      sonographic features of epidermoid cysts that may allow testis-sparing surgery.

PMID- 11441560
TI  - Primary cancer of the urinary bladder: CT evaluation of the T parameter with
      different techniques.
AB  - The evaluation of mural invasion (T) in primary urinary bladder carcinoma is
      important in the planning of an appropriate surgical or radiochemotherapeutic
      strategy. Previous investigators using computed tomography (CT) have evaluated
      the bladder filled with urine, urine opacified with iodinated contrast material,
      or air insufflation. The purpose of this trial was to establish which of these
      three techniques was the most accurate by comparing data obtained in
      postoperative staging (pT). Sixty-five patients with primary bladder cancer were
      enrolled, all of whom were studied by spiral CT with these three techniques.
      Patients were assigned to four stage groups: Ta-T1, T2-T3a, T3b, and T4. The
      results demonstrated total accuracies of 95% for the air-insufflated bladder,
      90.5% for opacified urine, and 87% for noncontrast studies. In conclusion, the
      air-insufflated bladder is the more accurate technique in the evaluation of the T
      parameter in primary bladder cancer, especially in the first and third stage
      groups.

PMID- 11441561
TI  - Metastatic adrenal tumor from clear-cell renal cell carcinoma: a pitfall of
      chemical shift MR imaging.
AB  - We present a case of adrenal metastasis from clear-cell renal cell carcinoma in
      which presence of a small amount of fat was shown on chemical shift gradient-echo
      magnetic resonance imaging. Radiologists should be aware that signal loss of the
      adrenal tumor on out-of-phase gradient-echo images does not always suggest the
      diagnosis of benign adenoma, particularly in patients with a history of renal
      cell carcinoma.

PMID- 11441562
TI  - Necrotizing perineal fasciitis in two paraplegic nursing-home residents: CT
      imaging findings.
AB  - Necrotizing fasciitis is a severe infection of the superficial fascia. Early
      recognition and aggressive management are essential to the treatment of this
      highly morbid disease. The clinical and physical findings are often the initial
      clues leading to the correct diagnosis. Computed tomography can play a crucial
      role in delineating the anatomy, evaluating for the extent of the infection, and
      for eventual complications. Before the advent of cross-sectional imaging, the
      majority of suspected patients underwent extensive surgical debridement
      procedures with resultant morbidity and mortality. We present two cases in which
      computed tomography played a major role in determining the need for emergent
      surgery and conservative management.

PMID- 11441563
TI  - Functionally-generated pathway theory, application and development in Cerec
      restorations.

PMID- 11441564
TI  - Time to take stock.

PMID- 11441565
TI  - An indirect/direct method for contouring and finishing Cerec restorations.

PMID- 11441567
TI  - Internet news--surfed for you.

PMID- 11441566
TI  - The Trojan horse in the age of computers.

PMID- 11441568
TI  - Enhancing implant surgery planning via computerized image processing.
AB  - Computerized tomography (CT) and magnetic resolution imaging (MRI) are the
      medical imaging modalities to deliver cross-sectional images of the human body. 
      In the last decade, CT has become the most frequently used imaging modality for
      the evaluation of the jaw for dental implants.  Furthermore, image reformatting
      software has been developed in  order to obtain a correct preoperative diagnosis
      and treatment planning regarding osseointegrated implants.  Previous work has
      shown that CT images are affected by a distortion ration from 0% to 6%.  This
      might be due to the alignment of the patient during scanning, to his/her
      movements, or possibly to the saturation of pixels composing the image.  In order
      to solve the former problem, intraoral stents can be used to center the patient's
      head perpendicular to the axis of the implant to be inserted.  However, if more
      than one implant must be placed - possibly with very different axes - it would be
      necessary to acquire the corresponding number of tomograms, each perpendicular to
      the axis of one planned tooth. Obviously, it would be better not to expose the
      patient to multiple CT scanning.  In this work, we present a software approach
      for enhancing implants surgery planning in order to obtain exact morphological
      measurements of the bone and planned teeth with a single CT acquisition.  This is
      achieved by applying image-processing techniques to the original CT images, in
      order to produce new Ct images lying on different planes, and possibly
      perpendicular to a different tooth.  The resulting software system (Dental/Vox)
      has been implemented in C+ + and runs on Intel-based personal computers under the
      Windows operating systems. DentalVox ensures better mechanical results in the
      design and planning of a dental implant compared to other, similar software
      tools; it can reconstruct axial (and panorex and cross-sectional) images once any
      direction is chosen.  This makes it possible to implant a mechanically and
      esthetically superior prothesis in the underlying gnathic morphology.

PMID- 11441569
TI  - Natural history and clinical outcome measures for multiple sclerosis studies. Why
      at the present time does EDSS scale remain a preferred outcome measure to
      evaluate disease evolution?

PMID- 11441570
TI  - Binswanger's disease is not a single entity.
AB  - The clinicopathological findings reported by Binswanger are insufficient to
      qualify as distinct entity the condition named "Binswanger's disease", and
      subsequently by Olszewski (1962) "subcortical arteriosclerotic encephalopathy
      (SAE) (Binswanger's type)". A short summary of the characteristic pathological,
      clinical and neuroimaging features of SAE is reported. The white matter changes
      detected by neuroimaging must be considered aspecific, since identical changes
      may be found in normal elderly as well as in patients with different diseases:
      different biochemical mechanisms can undoubtedly underlie identical neuroimaging
      patterns. Two other relevant points are noteworthy: the occurrence of
      pathological features of SAE in other diseases (CADASIL, pseudoxanthoma
      elasticum, antiphospholipid antibody syndrome) and the observation of some
      patients with pathological changes of SAE but an incomplete clinical picture. The
      clinicopathological features described as Binswanger's disease do not qualify as
      a separate entity since they are common to a variety of illnesses. The
      pathological picture identified by Olszewski can rightly be named, according to
      Caplan, "chronic microvascular leukoencephalopathy" (CML). The
      clinicopathological features of the so-called Binswanger's disease constitute a
      syndrome, the CML syndrome (CMLS), which can be found in some hereditary diseases
      and in acquired conditions. This syndrome shows peculiar cerebrovascular changes
      and, when clinically associated with dementia, identifies one of the subtypes of
      vascular dementia.

PMID- 11441571
TI  - Botulinum toxin treatment for functional disability induced by essential tremor.
AB  - This study aimed to improve botulinum toxin's (BTX) efficacy and to reduce its
      unwanted effects in the treatment of functional disability due to essential
      tremor (ET) of the hand. Twenty patients with disabling ET, not responding to
      conventional pharmacological therapy, were enrolled in this open-label study.
      Activities of daily living self-questionnaire (ADLS) and severity tremor scale
      (STS) were used to establish patients' functional disability and tremor severity.
      Accelerometry and surface electromyography were used to identify the arm muscles
      with tremorogenic activity during impaired positions. Global rating was used to
      measure treatment efficacy and unwanted effects. BTX type A was injected into the
      muscles principally responsible for impaired positions. After BTX treatment,
      there was a significant reduction in both severity and functional rating scales
      scores (ADLS and STS) and of tremor amplitude as measured with accelerometry and
      EMG. Adverse effects were limited to a slight third finger extension weakness in
      15% of patients. BTX injections are effective and safe in reducing disability due
      to ET, if based on the criterion of functional selection.

PMID- 11441572
TI  - Type, causes, and prognosis of stroke recurrence in the province of Teruel,
      Spain. A 5-year analysis.
AB  - Recurrent strokes are an important cause of morbidity and mortality.
      Identification of the causes of recurrence and its treatment may play an
      essential role in the prevention of further strokes. The aim of our work is to
      analyze the type and causes of stroke recurrence in a 5-year period and to
      determine if recurrent stroke is of the same type as index stroke. In a
      retrospective study, we reviewed the clinical records and database of our
      hospitals and found a total of 1108 patients admitted because of primary stroke.
      The patients with recurrent stroke were selected for a comprehensive analysis.
      Age, vascular risk factors and fatality rates of these patients were compared
      with those obtained in recurrence-free patients. We identified 135 patients with
      recurrent stroke. The most frequent type of recurrence was large vessel
      atherothrombotic stroke followed by the cardioembolic or lacunar stroke. The
      major contributing factors were hypertension, atrial fibrillation, and
      cardiomyopathies. The fatality rate did not differ from the overall mortality by
      stroke in these years, but the majority of deaths occurred in long-term
      recurrences. The functional status was worse after recurrent stroke than after
      index stroke. Although any pattern of recurrence is possible, there is a major
      trend to occur in the same vascular territory by the same pathophysiologic
      mechanism. Recurrent stroke frequently carries a worse functional status than
      index stroke. In many patients, despite the appropriate treatment, stroke
      recurrence was an unavoidable consequence.

PMID- 11441573
TI  - Incidence of multiple sclerosis in Bagheria City, Sicily, Italy.
AB  - We investigated the incidence of multiple sclerosis (MS) in a Sicilian community
      located at sea level. The study was a retrospective search for MS patients.
      Incidence was studied in the period from 1 January 1985 to 31 December 1994. We
      searched for definite MS patients, according to Poser's criteria, among the
      population resident in Bagheria (Palermo province). There were 25 subjects
      affected by MS, of which 20 were incident MS patients. The average annual
      incidence was 4.4 per 100,000 persons (n = 453,385 person-years). The incidence
      increased over time (1985-1989 = 3.5, 1990-1994 = 5.3). A parallel decrease of
      the interval between onset and diagnosis of MS was observed (1985-1989, 3.7
      years, 95% CI = 1.6-7.3; 1990-1994, 1.9 years, 95% CI = 1.0-3.3). These results
      confirm that MS is frequent in Sicily.

PMID- 11441574
TI  - Peroneal mononeuropathy: predisposing factors, and clinical and
      neurophysiological relationships.
AB  - The most common mononeuropathy in the lower extremity involves the nerve. We
      retrospectively evaluated the etiological predisposing factors and clinical
      neurophysiological features of 36 patients affected by peroneal mononeuropathy
      (PM). In 30 patients, a clear predisposing factor was identified. PM was more
      frequently perioperative (11 cases), associated with axonal involvement.
      Unexpectedly, PM was not only due to surgery close to the peroneal region, but
      was mostly associated with hip surgery and, rarely, with thoracic-abdominal
      surgery. A postural predisposing factor of PM was also frequently observed,
      usually associated with a pure conduction block. Conversely, most patients with
      bedridden predisposing factor presented axonal involvement, which was rarely
      associated with conduction block. In 25 of 36 PM cases, a long-term follow-up
      lead to an improvement (12 cases) or to good recovery (13 cases) of PM. In
      conclusion, our study shows that: (1) in most PM cases it is possible to identify
      a predisposing factor; (2) there is a good correlation between predisposing
      factor and neurophysiological involvement, and (3) PM usually has usually a good
      prognosis.

PMID- 11441575
TI  - Alcohol-sensitive hereditary essential myoclonus with dystonia: a study of 6
      Brazilian patients.
AB  - We present the clinical profile of a group of patients with myoclonus and
      dystonia sensitive to alcohol and address these cases in the context of essential
      myoclonus. Six patients from 4 families were selected: 4 men and 2 women with
      myoclonus affecting predominantly the arms. Active movements of these segments
      elicited the dystonic and myoclonic movements. A marked improvement with alcohol
      intake was seen. Laboratory findings including EEG, SSEP, and cranial CT and MRI
      were normal. Surface EMG recording showed bursts with duration of 30-112 ms in 3
      patients. One patient showed a triphasic recording pattern (agonist-antagonist
      agonist) of ballistic type. Our findings suggest that the myoclonus-dystonia
      disorder is present in Brazilian patients.

PMID- 11441577
TI  - Epidemiology of multiple sclerosis. Does this really point toward an etiology?
      Lectio Doctoralis.

PMID- 11441578
TI  - A case of spontaneous arm levitation in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy is one of the parkinsonial syndromes causing
      atypical parkinsonism. In recent reports, other than subcortical involvement,
      also cortical structures have been shown to be involved in progressive
      supranuclear palsy patients. One of the clinical presentations of this
      involvement is spontaneous arm levitation which is a component of alien limb
      syndrome. Here we report a clinically diagnosed progressive supranuclear palsy
      patient with spontaneous arm levitation. Clinically spontaneous levitation of one
      arm without denial of ownership suggests the presence of spontaneous arm
      levitation. Spontaneous arm levitation can occur in the setting of progressive
      supranuclear palsy and it possibly demonstrates the cortical involvement in this
      disorder.

PMID- 11441579
TI  - Ante litteram description of atypical parkinsonian cases.
AB  - We have searched in the neurological literature for cases of atypical
      parkinsonism published before the epidemic encephalitis era. Some of these cases
      can be recognized. Therefore the epidemic encephalitis has no etiological
      importance in these clinical syndromes.

PMID- 11441580
TI  - Spinal cord lesion due to epidural anesthesia.

PMID- 11441581
TI  - HIV/AIDS CME--logical changes.

PMID- 11441582
TI  - Cardiac tamponade: an unusual clinical presentation.
AB  - Pericardial effusion with cardiac tamponade is an unusual presentation of
      lymphoma, although cardiac involvement is often a late finding in widespread
      malignancy. Clinical identification can be difficult ante-mortem. New cardiac
      symptoms or classic findings of cardiac tamponade should prompt aggressive
      investigation. We present a case of B-cell lymphoma that initially presented as
      pericardial effusion with tamponade and discuss the characteristic physical
      findings and radiographic data that assist in diagnosis.

PMID- 11441583
TI  - Vermont Oxford Network: effective and efficient medical care for the neonate.
AB  - The Vermont Oxford Network is a non-profit, voluntary collaboration of health
      care professionals supported by membership fees and research grants which
      collects data from 310 intensive care units located in the United States and in
      many countries around the world. Data are collected on infants between 401-1500
      grams and this data is entered into an international database. The information
      generated by the Vermont Oxford Network can be used for comparisons among
      hospitals providing similar levels of care. Medical problems can be identified
      and quality improvement projects implemented. This network also provides an
      opportunity to participate in randomized clinical trials, serves as an
      educational tool for the hospital staff, and the information provided helps the
      physician practice evidence based medicine in an efficient manner. Currently four
      hospitals in Kentucky are participating in this network and the University of
      Louisville Hospital has participated in two controlled, randomized studies.

PMID- 11441585
TI  - OxyContin abuse.

PMID- 11441584
TI  - On persuasion.

PMID- 11441586
TI  - Recent advances in hepatitis C.

PMID- 11441587
TI  - [Latex protein allergy and preventive measures].
AB  - Numerous studies and documents have been recently produced on the topic of latex
      allergy but the unpredictable nature of the clinical reactions and the widespread
      use of natural rubber products in health care has led to incorrect use due to
      inadequate risk assessment. This article is intended to supply a clinical and
      epidemiological outline of latex allergy and its management and prevention. The
      aim is to promote communication between specialists in various disciplines in
      order to protect patients and health care workers from the risk of latex allergy.
      The feasibility analysis of a latex-free stream in a hospital was made by a board
      composed of an allergist, occupational health physicians, a surgeon and an
      anaesthetician to evaluate the various phases of the project. The equipment
      available at the hospital (certified latex-free materials to equip pre and post
      operation trolleys, latex free gloves) and a correct work organization
      (definition and work procedures, check list of materials, alarm bracelet, warning
      signals) will make it possible to achieve a latex-free stream for symptomatic and
      sensitized patients at risk. The use of non-powdered gloves with low levels of
      protein residue, particularly in areas like operating theatres, can minimise the
      occurrence of sensitization to latex, protecting health care workers from serious
      consequences. Also, such measures reduce the cost of health surveillance, allow
      latex-safe areas to be maintained which can be inter-connected so that the best
      possible management ot latex-allergic patients during hospitalization is ensured.

PMID- 11441588
TI  - [Tetanus prophylaxis. Proposed rationalization of procedure in the occupational
      field].
AB  - After a recent increase in cases of tetanus in Italy, the Ministry of Health has
      proposed vaccination of the entire population, inviting local physicians to
      cooperate towards this end. The author suggests periodic dosage of tetanus
      antitoxin antibodies as the most economic and efficient method of identifying
      workers who are not protected by vaccination.

PMID- 11441589
TI  - [Four-year follow-up of a group of workers with allergic sensitization employed
      in breeding of insects for biological pest control].
AB  - In two previous papers we reported allergic diseases in workers employed in
      breeding insects for biological pest control. It was found that Ephestia
      kuehniella, Orius laevigatus and other insects caused allergic
      rhinoconjunctivitis and asthma. The aim of this new study was to assess the
      relationship between the implementation of the recommended preventive measures
      and the decrease in sensitization in exposed workers. We performed a four-year
      follow-up of exposed workers, using the prick test and RAST with specific
      allergens and pulmonary function test at the end of the work shift. The results
      showed a decrease in skin test sensitization for Orius and Ephestia, a decrease
      in allergic diseases in the previously studied workers, and no symptoms in
      recently employed workers. These results confirm the validity of the recommended
      preventive measures: semi-closed cycles, gloves, protective masks, overalls and
      sunglasses.

PMID- 11441590
TI  - Comparison of certain biochemical changes during exercise tests on treadmill and
      bicycle-ergometer with equal workload intensity.
AB  - Ergometrics, using both treadmill (T) and bicycle-ergometer (B), plays an
      important role in assessing physical work capacity. In addition to the other
      important parameters (blood pressure, heart rate, oxygen consumption, oxygen and
      carbon dioxyde-partial pressure in blood, etc.), it is of interest to follow,
      measure and compare values of certain metabolic products immediately after
      completion of exercise on T and B. The aim of this study was to define which test
      develops the most significant changes in metabolic parameters when the same
      workload intensity is maintained. The metabolic parameters measured were:
      lactate, pyruvate, 2.3-diphosphoglycerate (2.3-DPG), lactate dehydrogenase (LDH)
      and aldolase activity. The mean values obtained at the end of both tests were:
      lactate 3.17 mmol/l +/- 1.017 mmol/l (T) and 4.28 mmol/l +/- 1.2 mmol/l (B);
      pyruvate 78.17 mumol/l +/- 30.32 mumol/l (T) and 92.16 mumol/l +/- 32.73 mumol/l
      (B); 2.3-DPG 3.58 mmol/l +/- 1.31 mmol/l (T) and 3.93 mmol/l +/- 1.44 mmol/l (B);
      LDH activity 239.22 U/I +/- 38.24 U/I (T) and 260.5 U/I +/- 61.27 U/I (B);
      aldolase activity 4.93 U/I +/- 1.45 U/I (T) and 5.88 U/I +/- 2.31 U/I (B). The
      results obtained indicate that a much higher production and/or lower elimination
      of acid metabolic products occurs during the test on B. This is most likely due
      to increased muscle pressure in big muscle groups in the legs which, by
      compressing the local blood vessels, diminish oxygen supply and the elimination
      of acid metabolic products. According to the results of the study, the use of T
      can be recommended as a more appropriate method for physical work capacity
      assessment of untrained individuals in occupational medicine.

PMID- 11441591
TI  - [Summary of recommendations for a rational implementation of the ministry of
      health guidelines on the prevention of occupational risks in handling
      antineoplastic agents].
AB  - The Italian Society of Preventive Medicine for Health Care Workers has examined
      the guidelines recently published by the Italian Ministry of Health for
      implementation of safe handling practices for antineoplastic drugs and produced
      recommendations. On the basis of literature data and the field research carried
      out by the Society, different aspects covering risk assessment, environmental and
      biological monitoring, workplace and individual protection measures, education
      and training of health care and technical personnel, health surveillance
      programs, were focused on. The creation of a single central unit for preparing
      antineoplastic drugs or at least a drastic reduction in the number of preparation
      units currently operating in each hospital are the most relevant objectives of
      both the guidelines and the Society document. This must be accompanied by correct
      management of technical and organizational measures, improvement of safety and
      health of personnel involved in different activities and reduction of the number
      of exposed subjects. Finally the importance is stressed of clear specific
      mandatory procedures with which to manage and control the different aspects of
      job organization.

PMID- 11441592
TI  - [Delphi study in the identification of research need in occupational medicine in
      Italy].
AB  - The aim of the study was to identify the research priorities and strategies in
      Occupational Safety and Health (OSH) in Italy with a high degree of consensus.
      Based on the Delphi technique, a two-phase questionnaire was sent to experts at
      Universities, Local Health Units (ASLs) and Trade Unions. In the first phase,
      experts were requested to indicate three research topics in the OSH sector. A
      total of 27 topics for both universities and ASLs and 18 topics for Trade Unions
      were identified. In the second phase, experts were requested to assign a score
      from one (low relevance) to five (high relevance) to each topic previously
      identified. On the basis of a mean score reported for each topic, two ranked
      lists of priorities, one referred to universities and ASLs the other referred to
      Trade Unions, were formulated. The highest priority identified by universities
      and ASLs was occupational carcinogenesis, followed by quality in occupational
      medicine. Workers' information, education and participation was also identified
      with a high degree of priority. For Trade Unions, occupational cancers as well as
      training, information, participation and prevention awareness had the highest
      priority. Trade Unions also identify small-industries and occupational accidents
      as topics with high priority for research development. This study allowed a high
      degree of consensus to be reached regarding the research priorities in the OSH
      sector in Italy. Differences in the topics identified, or regarding the mean
      score of topics commonly identified, were related to the origin of the expert
      recruited to this study (University, ASLs or Trade Unions) and, for universities
      and ASLs, to the geographical area. In the authors' opinion, the full transfer of
      existing scientific data to occupational health practice and the harmonization of
      the priorities identified by this investigation are crucial if the research needs
      in the OSH sector in Italy are to be met.

PMID- 11441593
TI  - Observation of acoustic cavitation bubbles at 2250 frames per second.
AB  - Acoustically induced cavitation at 20 kHz is observed by means of high speed CCD
      recording at a frame-rate of 2250 per second. Using digital image processing the
      bubbles' trajectories are reconstructed. The experimental data reveal that
      collision and coalescence of bubbles is a predominant phenomenon that limits
      their individual lifetime. Measurements of bubble sizes and velocities are in
      agreement with previous results.

PMID- 11441594
TI  - Spatio-temporal dynamics of cavitation bubble clouds in a low frequency reactor:
      comparison between theoretical and experimental results.
AB  - The propagation of ultrasound through a liquid induces the growth of inceptions
      and germs into bubbles. In a low frequency reactor, fragmentary transient bubbles
      emerge due to the acoustic driving. They violently collapse in one cycle and
      fragment into many smaller bubbles than in turn cavitate. This violent collapse
      is responsible for the mechanical effects of ultrasounds effects. The latter
      bubbles gather in a ball-shaped cloud and migrate to pressure antinodes. During
      their migration, their nonexplosive collapses mainly contribute to activate
      chemical reactions by producing OH. radicals. Mathematical modelling is performed
      as a new approach to predict the bubbles field. Through numerical simulation, we
      determinate emergence sites of mechanically active cavitation bubbles. Calculus
      are compared with aluminium foil degradation. The modelling of bubble migration
      allow us to have an insight on the privileged sites of the chemical reactions.
      Validation of the modelling is made through direct comparison with
      chemiluminescence photo. All experiments and computations are made in a 28.2 kHz
      sonoreactor.

PMID- 11441595
TI  - Preliminary results on the effect of power ultrasound on nitrogen oxide and
      dioxide atmosphere in nitric acid solutions.
AB  - The effect of ultrasound (20 kHz, 3 W cm-2) on the kinetics of HNO2 and H2O2
      formation was investigated in a 1 M HNO3 medium for NO2-Ar and NO-Ar gas mixtures
      in various volume fractions (f(NO2) < 1.7 vol% and f(NO) < 1.1 vol%,
      respectively). The H2O2 formation rate measured in 1 M HNO3 in the presence of
      N2H5NO3 was observed to be much lower than that of HNO2 without N2H5NO3, and was
      relatively independent of the NO2 or NO gas volume fractions in the argon
      atmosphere. The HNO2 formation rate increased under ultrasound, and was higher
      with NO than with NO2. The induction period observed without ultrasound
      disappeared when ultrasound was applied. The first step in the sonochemical
      mechanism of HNO2 formation in the presence of NO2 involves thermal decomposition
      of NO2 into NO within the cavitation bubble. In the second step of HNO2
      formation, NO reacts either with HNO3 in the cavitation bubble, or with NO2 in
      the cavitation bubble or at the bubble/solution interface.

PMID- 11441596
TI  - High bubble concentrations produced by ultrasounds in binary mixtures.
AB  - It was discovered that simultaneous insonification and air blowing of different
      aqueous binary solutions such as water/sodium-dodecyl-sulphate (SDS),
      water/methanol or water/potassium-sulphate yields a very concentrated bubble
      cloud invading the whole vessel in a few seconds. After the end of
      insonification, this cloudiness remained in the solution for about 1 min. The
      phenomenon was investigated by computer-treatment of solution pictures recorded
      every second after the end of insonification. Turbidity appeared to increase with
      ultrasound power, and also with SDS concentration. During the disappearance of
      the cloud, a turbidity front appeared rising and spreading upward. This front was
      studied in the characteristic plane and interpreted as a spatial segregation of
      different bubble sizes rising with different terminal velocities. The bubble
      sizes involved were estimated to about 10 microns. Adsorption of surface active
      species are invoked to explain the cloud formation and its abnormally slow
      disappearance, but the occurrence of the phenomenon for potassium-sulphate salt
      remains unexplained.

PMID- 11441597
TI  - Asymmetric reactions in sonochemistry.
AB  - Sonochemical processes involved in asymmetric synthesis are reviewed. The goal of
      this overview is to provide a comprehensive picture about the fields of both
      enantioselective and diastereoselective reactions accelerated or initiated by
      ultrasounds. Since the most, in many cases comparative, data are available in
      heterogeneous metal catalysis, the emphasis will be placed on these
      enantioselective hydrogenations, however, other applications such as phase
      transfer catalysis etc. will also be cited.

PMID- 11441598
TI  - The effect of ultrasound on photochemical reactions.
AB  - Sonochemistry and photochemistry are based on very different physical phenomena,
      which a priori seems to exclude any possibility to observe more than a simple
      superposition of their respective effects. Literature data are examined, first
      the few studies devoted to sonochemical and photochemical reactions in cases
      where a direct comparison is possible. The second part is devoted to an analysis
      of experiments in which both irradiations are effected simultaneously. Cases
      exist from which it can be concluded, at least provisionally, that sonication is
      able to quench long-lived excited states, because of the intense streaming which
      enhances strongly the probability of collisional deactivations.

PMID- 11441599
TI  - Effect of ultrasound on ester hydrolysis in aqueous ethanol.
AB  - Kinetics of the acid-catalyzed hydrolysis of ethyl acetate in ethanol-water
      binary solutions were investigated without sonication and under ultrasound at 22
      kHz. Rate enhancements by 1.03-2.4 times were found with a minimum at 18 wt.% and
      a maximum at 45 wt.% of ethanol. The results suggest that ultrasonic acceleration
      of the reaction may be interrelated to the perturbation of the molecular
      structure of the binary solvent.

PMID- 11441600
TI  - Phase-transfer catalysis and ultrasonic waves II: saponification of vegetable
      oil.
AB  - Saponification of oils which is a commercially important heterogeneous reaction,
      can be speeded up by the application of ultrasound in the presence of phase
      transfer catalyst (PTC). This paper focuses on the ability of ultrasound to cause
      efficient mixing of this liquid-liquid heterogeneous reaction. Castor oil was
      taken as a model oil and the kinetic of the reaction was followed by the extent
      of saponification. The hydrolysis of castor oil was carried out with different
      PTC such as cetyl trimethyl ammonium bromide (CTAB), benzyl triethyl ammonium
      chloride (BTAC) and tetrabutyl ammonium bromide (TBAB) in aqueous alkaline
      solution. As hydroxyl anion moves very slowly from aqueous to oil phase, the
      presence of a PTC is of prime importance. For this purpose, cationic surfactants
      are selected. The sonication of biphasic system were performed by 20 kHz (simple
      horn and cup horn) and 900 kHz. It was found that CTAB was better than the two
      others and this could be related to the molecular structure of the PTCs. The
      effect of temperature was also studied on the saponification process. By
      increasing the temperature, the yield was also increased and this could be
      explained by intermolecular forces, interfacial tension and mass transfer.
      Saponification of three different vegetable oils shows that the almond oil is
      saponified easier than the two others and this could be related to their
      properties such as surface tension, viscosity and density.

PMID- 11441601
TI  - Dehydration of hydroxenin monoacetate in the presence of ultrasound.
AB  - Starting from hydroxenin monoacetate, vitamin A acetate is obtained in a E/Z
      mixture by dehydration. This result could be explained by the formation of a
      small amount of hydrochloric acid from trichloromethane under ultrasound
      irradiation and based on further experiments.

PMID- 11441602
TI  - Sonolytic degradation of volatile pollutants in natural ground water: conclusions
      from a model study.
AB  - In order to evaluate the possibilities of an ultrasound-based cleaning
      technology, the effects of sonication on pollutants in a contaminated natural
      ground water were investigated. After the discussion of the results from this
      model study on the sonolytic degradation of volatile organic compounds, some
      consequences are reported and the important role of water components is
      described. Furthermore, the use of sonication as a cleaning technology for
      polluted water is discussed based on the conclusions from this study.

PMID- 11441603
TI  - Ultrasonic degradation of 2:4:6 trichlorophenol in presence of TiO2 catalyst.
AB  - The degradation of trichlorophenol has been studied at different intensities of
      irradiation using ultrasonic horn by changing the power input to the system.
      Effect of presence of catalyst TiO2 and concentration of catalyst on the
      degradation rates has also been investigated. The rates of degradation are found
      to be higher at higher intensities in the absence of catalyst but reverse trend
      is observed in the presence of catalyst. Adsorption and desorption
      characteristics of trichlorophenol on TiO2 catalyst have been examined. The
      catalyst enhances the rates of degradation but it also adsorbs some amount of TCP
      during the degradation process protecting it from ultrasonic degradation. Thus it
      is essential to consider the adsorption and desorption kinetics to get proper
      estimates of the degradation rates when the rates of degradation of TCP are
      calculated by analyzing the residual concentration of the compound in the liquid.
      The degradation of the pollutant seems to take place in the liquid only and that
      too only after desorption of the same from the solid particles. Solid particles
      seem to play a physical role in the overall degradation scheme, providing
      additional surface cavitation.

PMID- 11441604
TI  - Ultrasound enhanced degradation of Rhodamine B: optimization with power density.
AB  - Degradation of Rhodamine B, a waste water dye effluent was studied under the
      influence of ultrasound. In the present study, optimization of this degradation
      was carried out with power parameters, namely, power density (W/ml) and power
      intensity (W/cm2) using different ultrasonic equipments. From the studies, it has
      been observed that the degradation does not increase indefinitely with an
      increase in the power parameters, but instead, it reaches an optimum value and
      then decreases with a further increase in the power parameters. Also, these
      optima were not the same in all the ultrasonic equipments in which these studies
      were carried out. Difference in the type of acoustic field generated may be
      responsible for the different power optima observed with different ultrasonic
      equipments. The comparative study of the degradation of Rhodamine B using various
      ultrasonic equipments establishes a relationship between the area-specific
      parameter (intensity) and the volume-specific parameter (density) of reactivity.

PMID- 11441605
TI  - Sonochemical degradation for toxic halogenated organic compounds.
AB  - This paper describes the degradation of p-chlorophenol using three different
      ultrasonic devices. The dissipated power in the reaction matrix was measured
      based on calorimetric method. The study showed that hydrogen peroxide can improve
      the sonochemical reaction and gases dissolved in reaction matrix can affect the
      process to a small extent. The reaction mechanism and kinetics of degradation
      were also investigated.

PMID- 11441606
TI  - Sono-oxidation treatment of humic substances in drinking water.
AB  - Currently humic substances are removed from the raw water prior to chlorination
      by the conventional coagulation and filtration method using aluminium sulphate.
      Application of high-intensity (> 10 W/cm2) ultrasonic irradiation in conjunction
      with oxidative process using commercial oxidants H2O2 was investigated as an
      alternative. Sono-oxidation and sonodegradation of natural and synthetic humic
      substances have been followed over time by measuring total organic carbon (TOC)
      and absorbance by ultraviolet spectrometer (UV-VIS). It took approximately 60 min
      to reduce TOC by half and to have a complete degradation of humic acid.

PMID- 11441607
TI  - Sono-photocatalytic degradation of 2-chlorophenol in water: kinetic and energetic
      comparison with other techniques.
AB  - The degradation of 2-chlorophenol in water was kinetically investigated using the
      following different techniques, employed either separately or simultaneously,
      always with the same experimental set-up: light irradiation (315-400 nm),
      sonication, photocatalysis with different types of TiO2, photocatalysis with
      sonication. The influence of the reaction volume and of different gas mixtures,
      containing Ar and O2, as well as O2/O3, was also investigated. Finally, an
      energetic comparison among these different techniques was performed, focused on
      an industrial application of some of them.

PMID- 11441608
TI  - Ultrasonic depolymerization of aqueous polyvinyl alcohol.
AB  - Ultrasonication has proved to be a highly advantageous method for depolymerizing
      macromolecules because it reduces their molecular weight simply by splitting the
      most susceptible chemical bond without causing any changes in the chemical nature
      of the polymer. Most of the effects involved in controlling molecular weight can
      be attributed to the large shear gradients and shock waves generated around
      collapsing cavitation bubbles. In general, for any polymer degradation process to
      become acceptable to industry, it is necessary to be able to specify the
      sonication conditions which lead to a particular relative molar mass
      distribution. This necessitates the identification of the appropriate irradiation
      power, temperature, concentration and irradiation time. According to the results
      of this study the reactors constructed worked well in depolymerization and it was
      possible to degrade aqueous polyvinyl alcohol (PVA) polymer with ultrasound. The
      most extensive degradation took place at the lowest frequency used in this study,
      i.e. 23 kHz, when the input power was above the cavitation threshold and at the
      lowest test concentration of PVA, i.e. 1% (w/w). Thus this study confirms the
      general assumption that the shear forces generated by the rapid motion of the
      solvent following cavitational collapse are responsible for the breakage of the
      chemical bonds within the polymer. The effect of polymer concentration can be
      interpreted in terms of the increase in viscosity with concentration, causing the
      molecules to become less mobile in solution and the velocity gradients around the
      collapsing bubbles to therefore become smaller.

PMID- 11441609
TI  - Crystallization of potash alum: effect of power ultrasound.
AB  - The influence of power ultrasound on the crystallization of potash alum was
      investigated. Experiments have been carried out in a batch stirred vessel. It was
      found that ultrasonic waves decrease the supersaturation limits and modify the
      morphology of the crystals produced. The average crystal size decreases with an
      increase of ultrasonic power. To investigate also the action of ultrasound on
      already existing crystals, crystals produced in silent conditions were suspended
      in saturated potash alum solution at various ultrasonic powers. The results show
      that ultrasound has also an abrasive effect on potash alum crystals for high
      power inputs.

PMID- 11441610
TI  - Influence of hydrostatic pressure and gas content on continuous ultrasound
      emulsification.
AB  - Ultrasound is one means among others of producing emulsions mechanically. Droplet
      disruption in sonicated liquid-liquid systems is considered to be controlled by
      cavitation. Both hydrostatic pressure and gas content of the liquids influence
      the probability and intensity of cavitation. Continuous ultrasound emulsification
      experiments were carried out to elucidate the effect of these parameters on the
      result of droplet disruption. Maximum energy density in the apparatus decreases
      with increasing hydrostatic pressure, probably due to partial suppression of
      cavitation which is the main mechanism of power dissipation. At constant energy
      density there is no significant influence of hydrostatic pressure on the
      emulsification result, however. Corresponding results were obtained for the
      influence of the gas content. Gas saturation or partial degassing prior to
      emulsification lead to a shift in maximum energy density. But, again, at constant
      energy density no clear effect on the droplet size of the emulsion is observed.

PMID- 11441611
TI  - Influence of ultrasound on adsorption processes.
AB  - One of the most popular means for removal of organic water pollutants found in
      small concentrations is by adsorption. An important step in adsorption processes
      is the regeneration of the adsorbent as it does not only affect the adsorption
      desorption cycle but also the expenses of the following process steps. State of
      the art regeneration of adsorbent resins is done by chemical methods. These
      require the use of organic solvents or inorganic chemicals and involve a
      difficult secondary separation step. Therefore, industry seeks for alternative
      methods to regenerate exhausted adsorbents. One of the discussed regeneration
      methods is desorption by ultrasound. Ultrasound does not only promote desorption
      but also enhances the mass transfer of sorption processes. We discuss the arising
      problems and basic effects when applying ultrasound during sorption processes in
      order to show the potentials of this desorption process. The focus is laid in
      particular on the influence of ultrasound frequency and intensity.

PMID- 11441612
TI  - Electroless copper coating of epoxide plates in an ultrasonic field.
AB  - This paper reports the study of ultrasonic irradiation effects on electroless
      copper coating on an epoxide resin. Several parameters were monitored, such as
      plating rates, practical adhesion and internal stress, versus varying acoustic
      powers at a constant frequency of 530 kHz. Exposure conditions were characterised
      by both transmitted power and interfacial mass transfer coefficients. Optimum
      conditions expressed in irradiation time and power were determined. The use of
      ultrasound during electroless copper plating affects the plating rates and the
      deposits properties, particularly the practical adhesion which increases whereas
      the internal stress decreases. Then, the changes in the coating mechanisms are
      discussed.

PMID- 11441613
TI  - Electrochemical behaviour of zinc in 20 kHz sonicated NaOH electrolytes.
AB  - This paper describes the influence of 20 kHz ultrasound upon the corrosion
      behaviour of zinc in NaOH electrolytes. A systematic study of the effects exerted
      by ultrasound on the electrochemical interface was first carried out, so as to
      determine the transmitted power and to characterize mass transfer at the
      electrode. Then attention was focused on the corrosion passivation mechanism of
      zinc in sonicated NaOH solutions (0.1 and 1 M). Investigations were carried out
      using electrochemical techniques to determine corrosion and passivation kinetics
      parameters. SEM analysis of the sonicated zinc surfaces provides complementary
      information on the oxide layer composition and structure.

PMID- 11441614
TI  - The extraction of rutin from flower buds of Sophora japonica.
AB  - The efficiency of extraction of rutin from Sophora japonica is improved by
      ultrasound but is dependent on the solvent employed. Rutin is a compound with
      antioxidant activity and aqueous solvents appear to be unsuitable for ultrasonic
      extractions due to the formation of free radicals from the insonation of the
      solvent. The application of ultrasound to methanolic extraction gave a
      significant reduction in extraction time and an increase in maximum yield.

PMID- 11441615
TI  - An overview of the ultrasonically assisted extraction of bioactive principles
      from herbs.
AB  - This paper presents a review of the ultrasonically assisted extraction of
      bioactive principles from herbs. Much of the work was carried out under European
      community grants under the COPERNICUS programme and in a COST D10 network. Some
      aspects of classical and non-conventional extraction procedures are also
      presented and briefly discussed.

PMID- 11441616
TI  - Ultrasound fibrin clot destruction in vitro in the presence of fibrinolytic
      agent.
AB  - Ultrasound fibrin clot destruction was investigated in vitro using electron
      microscopy and by monitoring the changes in the light transmission of clot debris
      suspension. It has been established that in the course of a combined action of
      ultrasound and fibrinolytic agent at high ultrasound intensities and short
      sonification periods, fibrin clot is disrupted mainly due to sonomechanical
      treatment, while fermentative lysis takes place in parallel and at a
      significantly lower rate. However, the streptokinase action prevails after
      ultrasound switching off and results in the prevention of clot debris
      conglomeration.

PMID- 11441617
TI  - Broad prospects for commercial application of the ultrasonic (cavitation) melt
      treatment of light alloys.
AB  - Theoretical and applied aspects of ultrasonic melt treatment are considered.
      Industrial applications of the cavitation treatment for degassing, filtration,
      and grain refinement are illustrated using data for commercial alloys. Some new
      fields of use such as semisolid processing, low-friction alloys, and natural
      composites are discussed. In general, wide prospects of commercial application
      for the ultrasonic melt treatment of light alloys are shown.

PMID- 11441618
TI  - Journal of Palliative Medicine's new affiliation.

PMID- 11441619
TI  - "But I have promises to keep".

PMID- 11441620
TI  - Response to "Perspectives on increased family reports of pain in dying
      hospitalized patients" (by J.L. Dahl).

PMID- 11441621
TI  - Knowledge: insufficient for change.

PMID- 11441622
TI  - Measuring the quality of dying.

PMID- 11441623
TI  - Stenting the sigmoid colon in a terminally ill patient with prostate cancer.
AB  - Large bowel obstruction in the terminally ill patient can be difficult to manage.
      We describe a patient with sigmoid colon obstruction caused by metastatic
      prostate cancer in the pelvis who required hospitalization because of severe pain
      and obstructive symptoms. Treatment with an endoscopically placed self-expandable
      metal stent allowed the patient to have immediate resolution of symptoms and to
      receive hospice care at home.

PMID- 11441624
TI  - Symptom frequency and severity in patients with metastatic or locally recurrent
      lung cancer: a prospective study using the Lung Cancer Symptom Scale in a
      community hospital.
AB  - PURPOSE: To define symptoms and therapeutic requirements for patients with
      metastatic or locally recurrent lung cancer. METHODS AND MATERIALS: Data were
      collected from 69 consecutive patients with locally advanced lung cancer seen in
      consultation at a radiation oncology facility serving a community hospital in
      Virginia. The Lung Cancer Symptom Scale, a validated quality of life instrument,
      measured the incidence of symptoms in this group. RESULTS: Average survival for
      the entire group was 7 months. Fifty-seven patients received 81 courses of
      radiation therapy, 33 directed at thoracic disease and 48 delivered to sites of
      metastasis. Thirty-three percent of those who received radiation therapy required
      treatment to more than one anatomic site. Every patient was symptomatic at the
      time of consultation, with the number (p = 0.001) and severity (p = 0.001) of
      symptoms they suffered worse in the patient group seen 0 to 3 months prior to
      death rather than 4 to 6 months prior to death. With the exception of cough,
      symptoms were marked in their severity. CONCLUSIONS: Patients with advanced lung
      cancer suffer frequent and severe symptoms that worsen in the final months of
      life. The appropriate timing and combination of radiotherapy and chemotherapy are
      yet to be resolved. Future studies will require use of validated quality of life
      instruments to better catalogue palliation and treatment toxicity.

PMID- 11441625
TI  - A very good death: measuring quality of dying in end-stage renal disease.
AB  - A case is presented of an exceptionally good death after discontinuation of
      dialysis, and the authors trace the evolution of their attempts at measuring
      quality of dying in patients with end-stage renal disease. The Dialysis Quality
      of Dying Apgar is based on the pediatric tool for measuring the condition of
      newborn babies. Previous research with termination of dialysis has revealed that
      staff, patients, and families characterize a good death as being pain-free,
      peaceful, and brief. The quality of dying tool has corresponding domains to which
      it adds advance care planning and non-pain symptoms. Quantification of patient
      deaths combined with descriptive narratives can be used to establish benchmarks
      for the provision of terminal care. Very good deaths need to be recognized and
      valued as goals for palliative medicine.

PMID- 11441626
TI  - Attitudes on end-of-life care and advance care planning in the lesbian and gay
      community.
AB  - Gay men and lesbians have special interests in documenting their preferences
      regarding advance care planning and end-of-life care. A 64-item survey instrument
      was developed to ascertain the preferences of this community regarding approaches
      to end-of-life care, viewpoints on physician-assisted suicide (PAS) and
      euthanasia, and practices regarding advance care planning. The survey was
      completed by 575 participants recruited through community-based health care and
      social service organizations serving the lesbian and gay community, primarily in
      the New York metropolitan area. Respondents represent a diverse group of women
      (36%) and men (63%) from various age, racial/ethnic, and religious/spiritual
      backgrounds; 10% were human immunodeficiency virus (HIV)-positive. Respondents'
      perspectives on end-of-life care are generally consistent with findings from
      other attitudinal studies of U.S. adults: a majority supported legalization of
      PAS and preferred a palliative approach to end-of-life care. However, the gay
      community sample revealed even stronger support for assisted suicide and
      palliative care. Although respondents completed advance directives at a higher
      rate than adults generally, the legal importance for gay men and lesbians to
      execute directives should encourage health care providers and community
      organizations to assume a larger educational role on advance care planning.
      Results confirm other reports on the need to address provider communication
      skills. It is speculated that the HIV epidemic was a major influence behind these
      results because of the overwhelming personal impact of the epidemic on most gay
      men and lesbians during the past two decades.

PMID- 11441627
TI  - Educational interventions to improve cancer pain control: a systematic review.
AB  - CONTEXT: Inadequate pain control is a dismaying reality in cancer patients.
      OBJECTIVES: To review studies on cancer pain control interventions, and describe
      their findings with respect to participants' attitudes and knowledge, pain
      management, and pain levels. DATA SOURCES: Computer searches were made in MEDLINE
      from January 1962, in PsychLIT from January 1974, and in CINAHL from January 1982
      to August 1999, using a search strategy based on a combination of key words.
      STUDY SELECTION: Computerized listings from these sources contained 383, 26, and
      85 articles, respectively. After exclusion of duplicates, abstracts, editorials,
      letters, and irrelevant articles, we retained for review 33 articles, of which 25
      (76%) were interventions targeting health professionals, and 8 (24%)
      interventions targeting patients and family caregivers. DATA EXTRACTION: Study
      reports were reviewed using the following structured framework: Intervention
      Setting, Study Methods, Process Assessment, and Pain Outcome Assessment
      (Attitudes and Knowledge, Pain Management, and Pain Relief/Quality of Life). DATA
      SYNTHESIS AND CONCLUSION: Educational interventions can successfully improve
      cancer pain knowledge and attitudes of health care professionals, but without
      having much impact on patients' pain levels. The most promising avenue for
      improving cancer pain control in ambulatory settings may be brief, nursing
      interventions targeting patients in combination with a daily pain diary. This
      review suggests that further progress may occur through incorporating a
      systematic and valid method of documenting daily fluctuation in pain levels, and
      ensuring that documented uncontrolled pain is followed rapidly by clinical
      reassessment and dose adjustment.

PMID- 11441628
TI  - Reflections on going home.

PMID- 11441629
TI  - Fighting for a peaceful death: a personal essay.

PMID- 11441630
TI  - Fundamentals of education: "Edu-Mentals".
AB  - As new accreditation standards for health professions education increasingly
      require end-of-life (EOL) curriculum and performance-based assessment, health
      professions educators struggle to shift through the educational literature to
      find core principles, practical strategies, emerging trends, and on-line
      resources to advance as educators. A new kind of resource is needed for educators
      in today's health care environment. Emerging literature in the field of faculty
      development and continuing education in health professions highlight key features
      of resources for health professionals. To be effective, this faculty development
      resource must be: timely, problem focused, practical, and easily accessible.
      Based on these principles, the Medical College of Wisconsin initiated a series of
      short, focused fact sheets for educators. Dubbed, "Edu-Mentals" to represent the
      fundamentals of education, the series was launched in late spring 2001 and
      consists of short, focused fact sheets for health care professionals based on the
      parts of a systematic instructional design process.

PMID- 11441631
TI  - Resolving conflict and making decisions.

PMID- 11441632
TI  - Advances in palliative care in Latin America and the Caribbean: ongoing projects
      of the Pan American Health Organization (PAHO).
AB  - The Pan American Health Organization (PAHO) is engaged in field demonstration
      projects in Latin America and the Caribbean to expand the availability and
      effectiveness of palliative care services. Workshops and calls for proposals
      address the multiple causes of inadequate palliative care services that are
      typical for countries in the developing world. These include regulatory barriers
      and drug interdiction policies that interfere with the medical use of opioids,
      lack of education among health professionals, and insufficient palliative care
      infrastructure.

PMID- 11441633
TI  - Asking the right question.

PMID- 11441634
TI  - Improving Care Through the End of Life: launching a primary care clinic-based
      program.

PMID- 11441635
TI  - The Franciscan program: a Canadian perspective.

PMID- 11441636
TI  - "Pseudo-conduction block" in a patient with vasculitic neuropathy.
AB  - A 63-year-old man presented with progressive asymmetric weakness and numbness in
      his hands of 2 weeks duration. Nerve conduction studies showed low amplitude
      motor evoked potentials of both median nerves. The right ulnar, left tibial and
      peroneal nerves had normal potentials on distal stimulation with markedly
      decreased amplitudes proximally, suggestive of "conduction block". Three weeks
      later, amplitudes were decreased throughout. The patient was diagnosed with
      vasculitis. The acute ischemic injury presumably resulted in axonal damage
      between the distal and proximal stimulation sites, with subsequent Wallerian
      degeneration.

PMID- 11441637
TI  - Electromyographic validation of the trapezius and serratus anterior muscles in
      military press exercises with open and middle grip.
AB  - Electromyographic activity of the trapezius muscle and serratus anterior muscle
      was analysed in 4 different modalities of military press exercises, each of them
      with 2 grips: open and middle. It was analyzed 24 male volunteers using a 2
      channel TECA TE 4 electromyograph and Hewlett Packard surface electrodes. The TS
      and SI muscles acted with high and very high activity in all the modalities of
      military press exercises. Statistically, they did not show significative
      difference in the performance of the exercises with open and middle grip,
      justifying the inclusion of this group of exercises with both grips for the
      physical conditioning programmes.

PMID- 11441638
TI  - Test-retest reliability of the soleus H-reflex in three different positions.
AB  - PURPOSE: H-reflex has been clinically useful in the diagnosis of radiculopathies,
      developmental disorders, and measurement of motoneuron excitability. However,
      variability of the H-reflex precluded its routine application. The purpose of
      this study is to evaluate the test-retest and within-subject reliability of the
      soleus H-reflex tested in three different positions. SUBJECTS: Seven men and
      eight women healthy volunteered (20-50 y) with no history of significant low back
      pain or radiculopathy consented to the study. METHODS: The soleus H-reflexes for
      both lower extremities were elicited and recorded using Cadwell 5200-A EMG unit
      and surface recording. The tibial nerve was electrically stimulated at the
      popliteal fossa using 0-5 ms., 0.2 pps pulses at intensity equivalent to H-max.
      Each subject was tested randomly in three different positions: pronelying, free
      standing, and standing while lifting 20% of his/her body weight. Signal were
      amplified (1-5 K) using surface electrodes applied on the soleus muscle at
      midline and 3 cm below the gastrocnemius musculotendinous junction. The peak-to
      peak amplitude and onset latencies of four separate traces were averaged for each
      trial. Subjects were re-tested within 10 days by the same tester following the
      same protocol. RESULTS: Test-retest reliability of the H-reflex amplitude ranged
      from r = .29 in prone position to r = .56 in the loading position. Within day
      reliability of the H-amplitude was high between the three different positions and
      ranged from r = .56 to r = .97. The test-retest reliability of the H-latency were
      extremely high and robust, with the coefficients ranged from r = .92 to r = .94.
      Also the within day reliability of the H-latency ranged from r = .96 to r = .99.
      CONCLUSIONS: Results indicated that, when the H-amplitude is the measure of
      choice, testing the H-reflex in standing and loading positions is more reliable
      than testing in pronelying. Also testing the subject during various procedures in
      the same session is more reliable than testing subject in different
      days/sessions. The H-latency is highly reliable in all three testing positions.

PMID- 11441639
TI  - Multichannel derived median nerve SEP compared to EEG in patients with vascular
      cerebral lesions.
AB  - In order to compare the sensitivity of multichannel derived median nerve SEP with
      EEG in vascular cerebral lesions we examined 22 normals and 23 patients. SEP
      components within the first 50 ms could be divided into main waveform patterns:
      (1) a W-shaped parietal pattern consisting of N20, P25, N35 and P45 in most
      cases. (2) a frontal pattern with P20 and N30 as well as possibly detectible N24,
      P28, P33, N40 and P50. (3) a central P22. Two younger normals showed a V-shaped
      parietal pattern with N20 and P35, a frontal pattern with P20 and N36, and
      central P22 with a remarkably long latency. All components could be analysed
      sufficiently by means of three representative electrode positions (stimulation
      right/left): P3/P4, C3/C4, and F3/F4, which reduces the expense of recording and
      analysing considerably. 21 patients (91.3%) showed abnormal results in SEP,
      whereas 14 patients (60.9%) in EEG. A three channel electrode array can increase
      the usefulness of SEP and detect cerebral dysfunctions in cerebral lesions in
      spite of normal EEG under routine examination conditions. Analysis of
      multichannel derived SEPs during treatment and recovery after stroke and search
      for the prognostic value in the acute stage of the disease should be done in
      future.

PMID- 11441640
TI  - On-line measurement of human CNS re-organization.
AB  - Based on measurements of relative phase and frequency coordination of time-space
      distributed firing of neurons in the human nervous system, methods have been
      developed with which it is possible to functionally re-organize the lesioned or
      not optimally functioning human central nervous system (CNS) and to measure on
      line the organization (the coordination dynamics) of the CNS non-invasively. By
      measuring the present coordination dynamics at different times with ongoing
      coordination dynamic therapy when exercising on a special coordination dynamic
      therapy device, the progress in re-organization of the lesioned CNS can be
      quantified. The coordination dynamic recording method is derived from
      measurements of natural firing patterns of single neurons in the human CNS. The
      method is explained with load changes in the healthy CNS and with essential
      improvement in CNS organization following coordination dynamic therapy in
      traumatic brain lesion, spinal cord lesion, stroke, cerebral palsy, and
      myelomeningocele. Evaluations of CNS re-organization are discussed with respect
      to usefullness and ethics.

PMID- 11441641
TI  - Central motor conduction studies in patients with Guillain Barre syndrome.
AB  - To study the central nervous system involvement in Guillain Barre (GB) syndrome,
      30 patients with GB syndrome were subjected to clinical evaluation, muscle
      testing as per Medical Research Council (MRC) scale, disability score on a 0-5
      scale and central motor conduction studies to abductor digiti minimum (ADM),
      abductor pollicis bravis (APB) and tibialis anterior (TA) bilaterally. Outcome
      was defined at the end of 3 months into complete, partial and poor. Their age
      ranged between 12 and 61 years (mean 3.2) and 11 of them were females. At the
      peak of weakness, the limb muscle power was grade 0 in 8, grade I-II in 10 and
      grade III-IV in 12 patients. Grade 5 disability was present in 12, grade 4 in 12
      and grade 3 in 6 patients. One of these patients had grade 3 muscle power.
      Central motor conduction time (CMCT) correlated with muscle power, disability
      score and outcome. Two of our patients expired during the acute stage and 23
      could be followed up till 3 months. Three patients recovered completely, 15
      partially and 5 had poor recovery. It can be concluded that mild prolongation of
      CMCT although occurs frequently in the patients with GB syndrome, however,
      pronounced slowing of CMCT is rare and may suggest central involvement.

PMID- 11441642
TI  - Electromyography in cycling: difference between clipless pedal and toe clip
      pedal.
AB  - The purpose of this study was to verify if there is electromyographic difference
      in biceps femoris (long portion), semitendinous, semimembranous and gastrocnemius
      (lateralis and medialis) muscles, using clipless pedal and toe clip pedal. Thirty
      seven triathletes answered a questionnaire about their preferred type of pedal,
      which showed that 5.4% used toe clip pedal and 94.6% used clipless pedal. Four
      male triathletes (age: 21.75 +/- 2.50 years old; cycling experience: 5.00 +/-
      2.45 years; preferred cadence: 83.75 +/- 7.5 rpm) rode their own bicycles on a
      stationary roller at 100 rpm. The subjects performed one trial with each type of
      pedal. Bipolar surface electrodes placed on right lower limb picked up the EMG
      signal during 6 s. A band-pass filter (10-600 Hz) was used. Two muscles
      (semitendinous and semimembranous) presented lower activity with clipless pedal
      for all subjects. Biceps femoris and gastrocnemius lateralis presented lower
      activity with clipless pedal for three subjects. This led us to conclude that
      there is less electromyographic activity with the use of clipless pedal.

PMID- 11441643
TI  - Electrophysiological assessment in neurogenic thoracic outlet syndrome.
AB  - OBJECTIVES: To evaluate the value of different electrophysiological techniques in
      the diagnosis of neurogenic thoracic outlet syndrome (TOS). MATERIALS AND
      METHODS: Two females, aged 22 and 30 years, with progressive weakness and wasting
      of the right hand with slight sensory disturbances. Needle EMG, motor and sensory
      conduction along median and ulnar nerves, sensory conduction of medial (MACN) and
      lateral (LACN) antebrachial cutaneous nerves. RESULTS: Chronic neurogenic atrophy
      in small hand muscles, more severe in lateral part of thenar eminency, reduced
      compound muscle action potentials (CMAPs) more severe by median than ulnar
      stimulation, and reduced amplitude of the SNAPs of ulnar and MACN were the main
      findings consistent with neurogenic TOS. Both patients had right cervical rib in
      radiography. CONCLUSIONS: Electrophysiological study is useful in the diagnosis
      of neurogenic TOS. Reduced amplitude of MACN and ulnar nerve SNAPs, predominant
      denervation in thenar eminency, and reduced amplitude of CMAPs, more by median
      than by ulnar stimulation, are consistent with the diagnosis.

PMID- 11441644
TI  - The effect of auditory stimulation on autobiographical recall in dementia.
AB  - Elderly individuals with mild-moderate ("high ability") or moderate ("low
      ability") dementia, answered autobiographical memory questions drawn from three
      life eras (remote, medium-remote, and recent), in familiar music, novel music,
      cafeteria noise or quiet. Recall was significantly better in the high-ability
      than the low-ability group, in sound than in quiet, and in music than in noise.
      Recall was significantly related to life era, declining from remote to recent
      memory. The superiority of recall in music compared with noise was apparent for
      recall from remote and medium-remote but not recent eras. The results are
      interpreted as favoring an explanation of the beneficial effect of auditory
      stimulation, predominantly in terms of enhanced arousal or attention deployment,
      with a possible subsidiary role for associative facilitation.

PMID- 11441645
TI  - Adult aging and listening patterns for spoken prose: spontaneous segmentation
      versus self-paced listening.
AB  - Young and older adults were allowed to control the delivery rate of spoken prose
      for later recall using two methods. In one method (spontaneous segmentation),
      participants were allowed to interrupt speech passages whenever they wished. In
      the other method (self-paced listening), speech passages were presented in
      segments, with participants allowed to initiate presentation of subsequent
      segments via a key-press. Older adults' segment sizes in the spontaneous
      segmentation condition were unchanged when the passages were presented for a
      second time. By contrast, pause latencies to initiating subsequent segments in
      the self-paced listening condition were affected by experience with the passage.
      Results suggested that the segment sizes selected in the spontaneous segmentation
      condition were driven by the linguistic structure and prosody of the speech,
      rather than reflecting ineffective metamemory on the part of the older adults.

PMID- 11441646
TI  - Cognitive functioning in the last year of life as a function of age, gender, and
      race.
AB  - Research has shown that many factors affect cognitive functioning. In this study
      cognitive functioning was analyzed using proxy reports concerning 17,135
      decedents included in the 1993 National Followback Mortality Study conducted for
      the National Center for Health Statistics. These responses form a representative
      sample of all U.S. residents over age 15 who died in 1993 (except for those in
      South Dakota, which did not participate). Decedents had more difficulty
      understanding where they were than remembering what year it was or in recognizing
      family members. Logistic regression models found that age, gender, and race were
      the most important predictors of these basic cognitive functions. Although
      increasing age was associated with more cognitive difficulties, men had fewer
      deficits than women and Black Americans tended to have fewer deficits than White
      Americans. Possible reasons for these findings are discussed as well as some
      general implications for health service provision.

PMID- 11441647
TI  - Effects of education on the quality of life, diet, and cardiovascular risk
      factors in an elderly Spanish community population.
AB  - An inverse relation between education and health has been reported, suggesting
      the importance of examining the underlying mechanism of this association. We
      examined whether cardiovascular risk factors, diet, and indicators of quality of
      life (mood, self-perceived health, social relationships, self-rated sensory, and
      dental adequacy) vary according to educational level among 352 old people (65-95
      years old) in the city of Oviedo (Northern Spain). Lower educational level (LE)
      was associated with unhappiness, poor social relationships, poor self-assessed
      health, and sensory, and masticatory problems. LE elderly consumed less
      vegetables and meat products and more carbohydrates. LE women had a lower
      contribution of proteins and lipids to their total energy intake as well as a
      lower vitamin A intake. Except for hypercholesterolemia, no differences were
      found for the cardiovascular risk factors studied. The educational level of old
      people has a strong influence on their quality of life, nutrient intake and food
      consumption. These findings may provide part of the explanation for the social
      gradient in mortality.

PMID- 11441648
TI  - Assessment of physical function in aging rodents: a strategy for improving
      preclinical testing.
AB  - Geriatric medicine has recently focused on the biological mechanisms contributing
      to disability in the activities of daily living (ADLs), with special emphasis
      given to the study of sarcopenia, an age-related decline in muscle mass.
      Explaining the etiology of sarcopenia may provide useful information for the
      development of targeted interventions, especially those that are pharmacological
      in nature. However, exploratory studies aimed at evaluating the long-term effects
      of a particular intervention are costly and time consuming in a clinical setting.
      Therefore there is a need for preclinical testing of the efficacy of
      pharmacotherapies. This review provides (1) example of factors that contribute to
      the incidence of disability; (2) the conceptualization of a widely accepted human
      model of disability applied to an animal model; and (3) information on the
      potential advantages that may be realized from such translational research.

PMID- 11441649
TI  - Relationship between circulating levels of sex hormones and insulin-like growth
      factor-1 and fluid intelligence in older men.
AB  - The relationship was investigated between baseline serum levels of total
      testosterone (T), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS),
      ESTRADIOL (E2), sex hormone-binding globulin (SHBG), insulin-like growth factor-1
      (IGF-1) and cognitive functioning in 25 healthy older men (mean age 69.1 years). 
      Cognitive tests concerned measures not sensitive to ageing (crystallized
      intelligence), and measures sensitive to ageing (fluid intelligence and verbal
      long-term memory).  Partial correlation coefficients (controlled for level of
      education) revealed significant associations of total T (r = -.52, p = -.009),
      SHBG  (r - .59, p = .002) and IGF-1 (r = .54, p = .007) with the composite
      measure of fluid intelligence test performance, but not with crystallized
      intelligence, nor verbal long-term memory.  Stepwise hierarchical regression
      analysis with the composite measure of fluid intelligence as the dependent
      variable showed that the contributions of SHBG,  total T, and IGF-1 were not
      additive.

PMID- 11441650
TI  - [Genetic diversity of Rh haplotypes among Chinese populations].
AB  - In the statistic study of Rh blood group system, whole Chinese data were re
      calculated for haplotype frequency and linkage ratio, according to Counting
      Method. All Chinese majority populations and minority populations were divided
      into different groups, and variety genetic calculations on their gene diversity
      and gene differentiation were also calculated. The results shown obvious genetic
      differences between and among Southern and Northern Chinese populations. UPGMA
      phylogenetic dendrograms was plotted and the tree demonstrated that the genetic
      relationship among 68 Chinese populations are well corresponded with their
      geographical and linguistic distribution.

PMID- 11441651
TI  - [Chromogranin A gene antisense transgenic mice and the tissue specific promoter
      of chromogranin A gene].
AB  - The vector pGAS1C-lacZ was constructed which contains cga promoter-lacZ and cga
      promoter-cga antisense cDNA two major parts. The pGAS1C-lacZ was integrated into
      genome of PC-12 cells and lacZ gene expressed in PC-12 cells. We cut the pGAS1C
      lacZ with Xba I and Sal I to get rid of the framework of plasmid pGAS1C-lacZ,
      then microinjected the other part which contains antisense DNA into female
      pronucleus of the fertile mouse eggs. All injected fertile eggs were transplanted
      into the oviduct of foster so that the injected eggs developed normally. We
      selected transgenic mice by PCR, and got 14 transgenic founders. The founders
      were hybridized with normal mice respectively to reproduce the offspring F1 of
      founders. We executed all the founders and took their adrenal glands to dye with
      X-Gal respectively. Paraffin sections of the dyed adrenal glands were used to
      determine the level of lacZ expression in transgenic mice, so we selected two
      founders which adrenal glands were dyed deeply, and remained their offsprings.
      Taking different tissues from the transgenic mice to dye with X-Gal respectively,
      and we found the lacZ gene expressed in the adrenal gland and pancreas, but not
      in the muscle and adipose tissues. This result shows the neuroendocrine tissue
      specific promoter of Chromogranin A gene.

PMID- 11441652
TI  - [Bovine alpha-sl-casein gene sequences direct expression of a variant of human
      tissue plasminogen activator in the milk of transgenic mice].
AB  - The fusion gene containing the promoter of casein gene, LAtPA minigene and 3'
      flanking sequences of casein gene was introduced into the fertilized eggs of mice
      by microinjection. Five positive transgenic mice were obtained. The concentration
      of LAtPA in the milk of one female transgenic mouse is 0.18 microgram/ml. This
      result showed that the LAtPA minigene could correctly express the bioactive LAtPA
      in the milk of the transgenic mouse under the control of the regulatory elements
      of the casein gene.

PMID- 11441653
TI  - [Studies of the origin of Chinese domestic fowls].
AB  - A total of 539 bases fragment of mitochondrial DNA D-loop region of six domestic
      chicken breeds (30 individuals) were sequenced and compared to that of red
      junglefowl, grey junglefowl, green junglefowl and Lafayette's junglefowl issued
      in GenBank, and the phylogenetic trees for the chickens constructed based on the
      D-loop sequences. The results indicated that the four species of genus Gallus had
      great differences between each other, the G. g. domesticus was the next of kin to
      red junglefowl in Thailand and its adjacent regions, and near of kin to red
      junglefowl in Indonesian, Lafayette's junglefowl, grey junglefowl and green
      junglefowl one by one in proper order, suggesting that the red junglefowl in
      Thailand and its neighbour areas sufficed as the matriarchic ancestor of Chinese
      domestic fowls. It was also discovered that the two subspecies of Thailand i.e.
      G. g. gallus and G. g. spadiceus should belong to one subspecies because of their
      far lower differentiation compared to that among the domestic breeds.

PMID- 11441654
TI  - [Estimation of phenotypic and genetic parameters for birth type and number of
      lambs born alive in hu sheep].
AB  - A total number of 458 litter records from 115 daughters of 26 stock rams
      collected at the Yuhang Hu Sheep Farm were analysed. The statistical analyses
      indicated that the proportion of 1 to 5 lambs per litter was 21.18%, 49.78%,
      25.76%, 3.06% and 0.22%, respectively. Rams significantly influenced birth type
      and number of lambs born alive in the ewes. Parity didn't affect significantly
      birth type and number of lambs born alive. Birth type of the ewes did not
      significantly influence their number of lambs born alive. The estimated
      heritability was 0.251 for birth type and 0.097 for number of lambs born alive.
      The genetic, phenotypic and environmental correlations between birth type and
      number of lambs born alive were 0.241, 0.008 and 0.181, respectively. The
      coheritability for birth type and number of lambs born alive was 0.038. These
      parameters indicated that birth type and number of lambs born alive were two
      different traits which were not closely correlated genetically. Early selection
      for number of lambs born alive based on ewe birth type was ineffective.

PMID- 11441655
TI  - [Mutations of genes affecting heart development of Drosophila].
AB  - Recent studies suggest that the basic molecular control mechanisms of early heart
      development are remarkably conserved in Drosophila, vertebrate and human being.
      Drosophila can be used as a prototype to explore the genetic basis of
      cardiogenesis in human being. Here, mutations of genes affecting heart
      development of Drosophila are produced by chemical mutagen methanesulfonicaeid
      ethyl. With staining of antibody expressed in heart precussor cells of
      Drosophila, 112 lethal lines were observed to show mutant phenotypes in
      pericardial cells. Of them, 32 lines differ in their mutant phenotypes from those
      of known genes. Analysis of cytogenetic mapping shows that they are located in 13
      chromosomal regions without known heart-related genes, which implies that these
      loci contain genes probably involved in the heart development.

PMID- 11441656
TI  - [QTL mapping of the root traits in rice seedling].
AB  - Drought resistance is one of the most important traits in rice abiotic study. The
      report here analyzed several major root traits affecting drought resistance
      expression with the double haploid population (DH) from ZYQ8 (indica)/JX17
      (japonica) containing 127 lines. After 10 days solution culturing, three rice
      root traits, Maximum Root Length (MRL), Dry Root Weight (DRW) and Root/Shoot
      Ratio of Dry Weight (RSR), were revealed existing significant difference among
      the DH lines. Using the constructed molecular linkage map from this segregating
      population, the QTL mapping was conducted among these three root parameters. MRL,
      DRW, and RSR were found being controlled by 2/1/2 QTLs respectively in JX17,
      2/0/1 QTLs respectively in ZYQ8. Phenotype variance could be explained by 16.4%
      and 17.0% for MRL, 16.4% for DRW, 10.4% and 19.9% for RSR in JX17, 19.6% and
      13.0% for MRL, 13.2% for RSR in ZYQ8. All these QTLs identified were distributed
      on rice chromosome 2, 3, 4, 5, 6, 9 and 10. Comparing with the other mapping
      results, one QTL for each trait (L169-CT106A for MRL, G45-G1314A for DRW, G62
      G144 for RSR) was identical with the results reported previously.

PMID- 11441657
TI  - [Analysis of QTL x environment interaction for rice panicle characteristics].
AB  - The development of molecular genetic linkage map has accelerated the
      identification and mapping of genomics regions controlling quantitative trait
      loci. A recombinant inbred line population derived from Zhenshan 97/Minghui 63
      was grown in two years. Mixed linear model approach was used to jointly identify
      QTLs and QTL x environment interactions for five panicle characteristics. Ten,
      three, six, eight and seven QTLs were detected for spiketets per panicle, grains
      per panicle, seed setting, panicle length and panicle setting density,
      respectively. They collectively explained 29.13%, 19.2%, 29.46%, 26.39% and
      35.76% of phenotypic variations for these traits, respectively. For the five
      traits, QTLs with increasing effects and decreasing effects could be
      simultaneously identified in high value parent and low value parent. QTLs for
      correlative traits clustering located in the similar regions. One QTL for panicle
      length, two QTLs for spikelets per panicle and three QTLs for seed setting
      performed significant interactions with environment. The contributions from
      interactions were slightly larger than that from the QTLs involved in the
      interactions. No QTL x environment interaction was detected for traits with high
      heritabilities such as grains per panicle and panicle setting density.

PMID- 11441658
TI  - [Re-analysis of wide compatibility in rice].
AB  - Utilization of heterosis between rice subspecies has fascinated rice breeders for
      several decades. One of the main obstacles is the hybrid sterility in the F1
      populations of subspecies crosses in rice. Wide compatibility varieties are
      considered to an important way to overcome the problem. But the genetics of the
      wide compatibility is controversial. This paper dealt with the problem through
      three kinds of triple crosses in which a wide compatibility variety, Ketan
      Nangka, was involved. Pollen fertility, spikelet fertility and the
      correlationship between the two fertilities were analyzed in the three kinds of
      triple crosses. The results suggested that male and female sterilities existed in
      indica-japonica hybrids at the same time, while the contribution of male
      sterility to spikelet fertility varied from cross to cross; The characteristic of
      wide compatibility in different triple crosses was coordinated with the hybrid
      sterility between the indica and japonica test varieties used; Ketan Nangka
      possessed the wide compatibility genes on the loci in which the male and female
      sterilities between the test varieties were involved; The genetics of wide
      compatibility gene S-5 fitted to one locus sporo-gametophytic interaction model.

PMID- 11441659
TI  - [Comparison of the detection of QTL for yield traits in different generations of
      a rice cross using two mapping approaches].
AB  - In the F2 and recombinant inbred populations of Zhenshan 97B/Milyang 46, RFLP
      linkage maps were constructed to detect QTL for yield and its component traits.
      Results indicated that QTL having substantial additive effects were generally
      detected in both F2 and recombinant inbred populations. In addition, the trait
      performances were measured either based on a single plant or on replicated trials
      in the recombinant inbred population hardly affected the detection of QTL of
      higher effects.

PMID- 11441660
TI  - [Molecular identification and mapping of a maize gene (Rf3) in S-type CMS using
      AFLP, RFLP and SCAR techniques].
AB  - The maize CMS-S near isogenic line (NIL) developed by author and the backcross
      progeny (BC1) derived from it were used to identify molecular markers linked to
      the Rf3 gene and subsequently determine its chromosomal location on the linkage
      map of maize. Bulk segreant analysis was performed using AFLP technique. From the
      survey of AFLP primer combination, two AFLP markers, (EcoRI-AGG/MseI-CAC and
      EcoRI-AAC/MseI-CAG), which were named RR6 and RR7 respectively, linked to the Rf3
      gene were identified. However, AFLP marker RR6 showed polymorphism between
      parents, and bulks were used to survey the available 100 individuals of the BC1
      population, 2 out of 100 shed recombination. The recombination-rate was 2%. The
      genetic distance between Rf3 gene and AFLP marker RR6, was approximately 2.0 cM.
      And then, the RR6 was successfully cloned and sequenced, primer synthesized and
      converted to SCAR marker so that PCR marker can be developed for the marker
      assisted selection. In RFLP analysis, marker RR6 linked to Rf3 was found to be
      located between RFLP loci asg20 and php20581b, and mapped on chromosome 2L.

PMID- 11441661
TI  - Studies of the inheritance of seed qualities and the exploitation of F2 heterosis
      in low gossypol strains in upland cotton.
AB  - Twenty cross combinations were made with 4 recessive glandless lines (gl2gl2
      gl3gl3) used as females and 5 dominant glandless lines (Gl2eGl2e Gl3Gl3) used as
      male parents to estimate the genetic variance components of kernel oil and
      protein content of seeds, oil and protein index, and kernel index using a genetic
      model for parents, F2 and F3. The results showed that all the analyzed traits
      were mainly controlled by additive effects. Oil content was controlled mainly by
      maternal additive effect, and other traits by direct additive effect. The average
      heterosis of F2 over mid-parent based on population mean was -1.99% to 1.11% for
      all these traits. It suggests that little inbreeding depression exists for F2 and
      F3 seeds. There were 75% and 60% of the F2 and the F3 combinations in which open
      pollinated seeds contained gossypol levels lower than 0.4 gkg-1. This result
      indicated that it is possible to screen and select high yielding F2 hybrids with
      a gossypol content lower than the regulated criterion and without lowering seed
      quality.

PMID- 11441662
TI  - [Expression of Trial in mammalian cell and its apoptosis activation in culture
      cells].
AB  - To develop a system for expression of Trail in mammalian cell. PCR and sequencing
      were used to clone and to confirm Trail gene. Then, we constructed the vector for
      expression of Trail in mammalian cells. HeLa cells, one of sensitive cell lines
      to Trail, were transfected with the vector DNA. After 48 h, flow cytometry was
      used to screen HeLa transfected by Trail. 19% of total cells happened to
      apoptosis. This study conforms that the production of Trail expressing in mammal
      cell can induce apoptosis and exhibit high bio-active. The results indicate the
      potential application of Trail to tumor immunotherapy.

PMID- 11441663
TI  - [Preclinic in the hospital. In-hospital emergency and rescue service in a large
      hospital].
AB  - BACKGROUND AND OBJECTIVE: Many hospitals have a special resuscitation service
      that is responsible for life-threatening emergencies outside the hospitals
      intensive care unit, i.e. in the wards and in patient-treatment areas. In
      contrast, there is generally no emergency service caring for patients, visitors
      or personnel outside of these areas. In order to provide emergency medical help
      in the entire hospital area, in 1999 we instituted an additional in-hospital
      emergency service to cover the larger hospital area. This paper describes the
      structure of our in-hospital emergency service and our experience in the first 26
      months after its establishment. PATIENTS AND METHODS: We analysed the emergency
      protocols of all 147 episodes, that had occurred within the first 26 months. We
      classified them according to type of disease and/or injury by using the NACA
      score (range 1 to 7) to assess the severity of disease and/or injury. RESULTS: 45
      episodes took place within one of the 17 hospital buildings. 92 requests for help
      came from the hospital service and treatment areas including walkways and
      passages, while 3 came from the immediate vicinity outside of the hospital. A
      total of 7 requests turned out to be pranks, and 31.3% responses proved to be
      unnecessary when the team arrived at the scene. Of the total of 125 treated
      cases, 30 had a NACA score between 4 and 6, denoting life-threatening injury
      and/or disease. 6 patients were found dead at the scene or died shortly after
      arrival of the team. 101 of the patients had to be admitted to the hospital's
      emergency room. CONCLUSION: Since its establishment, knowledge of the existence
      of our in-hospital emergency service has steadily increased within the hospital
      community. As a consequence, number of events have likewise steadily increased.
      We believe that a total of 20.4% life-threatening events underscores the
      importance of the service in our large and extended hospital area. We also feel
      that our adherence to the training and personnel requirements demanded of public
      emergency services is necessary in order to insure the quality and efficacy of
      the service. This is also important because of current intentions to use our in
      hospital service as a back-up and/or reserve for the community's public emergency
      services.

PMID- 11441664
TI  - [Lysis of an extensive thrombus in the internal carotid artery using a
      glycoprotein IIb/IIIa receptor antagonist].
AB  - HISTORY: A 55-year-old man was admitted with acute right-sided arm and leg
      paralysis and motor aphasia, which were regressing at time of admission. He was
      known to have had several episodes of abnormal motor function in the right arm
      resulting from transitory cerebral ischaemic attacks. He was a heavy smoker.
      INVESTIGATIONS: Cranial computed tomography (CCT) excluded acute bleeding and
      there was no evidence of a stroke. Duplex sonography showed a filiform stenosis
      at the origin of the left internal carotid artery (ICA) with an echo-poor
      structure in the distal lumen. Subsequent angiography demonstrated an inoperable
      thrombus adherent to the filiform left ICA stenosis and extending to the base of
      the skull. DIAGNOSIS, TREATMENT AND COURSE: The neurological symptoms regressed
      over 24 hours, confirming the diagnosis of prolonged ischaemic neurological
      deficit. CCT having excluded bleeding, but significant left ICA stenosis by a
      thrombus having been demonstrated, treatment with acetyl salicylic acid (aspirin)
      and heparin was initiated. After the described angiographic confirmation of a
      thrombus adherent to the filiform stenosis, treatment with Tirofiban, a
      glycoprotein (GP) IIb/IIIa receptor antagonist, was begun and the thrombus
      completely dissolved. The filiform ICA stenosis was then treated surgically.
      CONCLUSION: This case demonstrates complete lysis of a long thrombus in the ICA
      by Tirofiban, making a primarily inoperable stenosis amenable to surgical
      intervention. It is not yet clear whether administration of GP IIa/IIIb receptor
      antagonists provides a therapeutic option in the treatment of intracranial
      arterial thromboses.

PMID- 11441665
TI  - [Homozygous form of factor V Leiden mutation as the cause of a myocardial
      infarction in patient with an unremarkable coronary vascular system?].
AB  - HISTORY AND ADMISSION FINDINGS: A 32-year-old smoker was referred to our hospital
      for the evaluation of acute chest pain. 9 years earlier he had had a non Q-wave
      myocardial infarction. At that time, angiography showed widely patent coronary
      arteries without atherosclerotic lesions. INVESTIGATIONS: Electrocardiographic as
      well as creatine kinase patterns were consistent with an acute transmural
      myocardial infarction. Cholesterol, triglyceride und homocysteine levels were
      normal. The patient was homozygous for the factor V Leiden mutation. TREATMENT
      AND COURSE: Thrombolysis was performed with streptokinase followed by coronary
      angiography showing a patent left coronary system and a non-occlusive thrombosis
      in the distal part of the right coronary artery. Body weight adapted abciximab
      infusion was started immediately. 9 weeks later coronary angiography was
      repeated. Now, in the distal part of the right coronary artery a minor dissection
      was seen followed by a not flow-limiting stenosis. CONCLUSION: On the evidence of
      this case history, we think it possible that the pronounced thrombophilia created
      by the homozygous factor V Leiden mutation may provoke myocardial infarction even
      if the atherosclerotic lesions are still too trivial to be detected by
      angiography.

PMID- 11441666
TI  - [Chronic lymphocytic leukemia. 1. Diagnosis].

PMID- 11441668
TI  - [Noncompliance: an overview].

PMID- 11441667
TI  - [Chronic lymphocytic leukemia. 2. Therapy].

PMID- 11441669
TI  - [Hypercholesteremia].

PMID- 11441670
TI  - [Conservative therapy for spondylolisthesis].

PMID- 11441671
TI  - [Evaluation of the public health service law of the Saxony-Anhalt region-
      community affairs, transfer of power and loss of control].
AB  - AIM: In the state of Saxony-Anhalt, a new Public Health Service law came into
      force in 1998. Our study investigated whether this new legislation has led to an
      extension of duties performed by regional health departments and to a subsequent
      increase in expenditure. METHODS: Guided interviews at all administrative levels
      of the public health system were conducted. The catalogue of duties was
      systematized and a questionnaire was developed and distributed to all regional
      health departments (response rate: 17 out of 24). Data concerning revenues and
      expenditures of the regional health departments were analysed on the basis of the
      administrative districts' budget data. RESULTS: Regional health departments
      stated that there had been practically no change in their activities over the
      last few years. When questioned about the coverage of 58 specific duties, a
      considerable disparity was evident between departments. A core group of
      "classical" duties comprising environmental health and hygiene, child health
      protection, individual health appraisal, and public health supervision are
      carried out on an established basis. Some duties were handled by external
      institutions, others, mostly community health duties, were not performed on an
      extensive scale. When asked about the desired model for their health department,
      most departments preferred the model of being an executor of sovereign duties,
      however a corporate model was deemed to be almost as acceptable. The following
      fields will gain increasing significance in the future: environmental medicine,
      health reporting, preventive medicine, co-ordination of regional health care, and
      health promotion. Since 1995, staff has been reduced in all regional health
      departments (-10.4%; 1999: 2.92 employees per 10,000 inhabitants). In 1999,
      expenditures amounted to an average of 24.64 German Marks per capita (range 14.20
      44.58 DM). The number of inhabitants and the revenue of the regional districts
      were determinants of their health budgets. CONCLUSION: Our results showed that no
      uncompensated additional expenditure by regional authorities resulted from this
      law. So far, most districts have not perceived regional health as a community
      affair offering possible competitive advantages. The federal state lost
      considerable influence at the regional level. Recommended are regional health
      priorities, conjoint staff development, and state guidance by a head agency
      providing leadership and support, while leaving responsibility with the
      districts.

PMID- 11441672
TI  - [Expectations and satisfaction of patients during inpatient treatment].
AB  - PURPOSE: Aim of the study was to examine the expectations of patients at the
      beginning and the satisfaction at the end of a hospital stay. The hospital
      settings were standardised. METHODS: 510 patients on the cardiological ward were
      asked to fill in a questionnaire on the first and last day of their stay.
      RESULTS: The admitted patients stated clear expectations in respect of the
      hospital facilities and staff. The most important aspects for the patients were
      the qualification of staff and the time physicians and nurses would devote to the
      patient, and the medical and technical equipment of the hospital. Beds per room,
      food, length and costs of the stay were less important in patients' expectations.
      On the day of discharge, the patients were very satisfied with the staff and
      medical equipment, in contrast to a low satisfaction regarding additional fees
      and the number of beds per room (three). CONCLUSIONS: Since cost-benefit is a
      basic need in running a hospital today, financial resources should be enhanced in
      the spheres which are equally medically important for fulfilling the expectations
      of the patients. Therefore, the number of staff and the qualification of the
      medical professionals should be financed instead of supporting architectural and
      room design. Accordingly, the patients' main criteria for choosing a hospital is
      the medical equipment provided and the qualification of the medical staff. In
      conclusion, these aspects should be publicized for meaningful decision-making.
      Medical professionals should be encouraged to inspire competence and to spend as
      much time as possible with each individual patient.

PMID- 11441673
TI  - [Significance of selected preventive, therapeutic and rehabilitation services
      reflected in a population survey].
AB  - BACKGROUND: Statutory health insurance bodies in Germany are experiencing
      increasing deficits, which raises the demand for rationalising health benefits.
      This, however, requires the establishment of priorities unless absolutely
      necessary benefits have to be cut. In other words, we must examine the
      preferences, expectations and experiences of the insured population. Within the
      framework of this study, we tried to find out the preferences and assessment of
      health services by the German population in the Lubeck region. DESIGN: Mail
      survey (questionnaire and two reminders) to register the preferences and
      attitudes to guaranteed medical services in the light of threatening deficits.
      The random sample was drawn by the residents' registration office in Lubeck, the
      criteria being an age of between 25 and 64 years, German nationality and
      principle domicile in Lubeck. INSTRUMENT: Postal questionnaire with 7 pages
      including 9 question complexes on the importance of preventive, curative and
      rehabilitative health services with 88 items and personal data. RESULTS: We
      succeeded in contacting 992 persons and achieved a response rate of 64.1%. 67% of
      the participants (n = 634) conveyed about their opinion on economic decisions in
      health care. 12% refused any involvement. In respect of importance and the cost
      of medical interventions, preventive, curative and rehabilitative interventions
      for children have highest priority. In the curative and rehabilitative sphere the
      emphasis lies on the severity of the illness. Interventions with controversial
      effectiveness were rated less important by the respondents and hence these should
      not be financed by the health insurance companies in every case, in the opinion
      of the persons who had been questioned. CONCLUSIONS: The evaluation shows that
      most participants could cope quite well with this questionnaire and were ready to
      be involved in decisions concerning health care. Like the participants of Ann
      Bowling's survey about the investigation of preferences in the UK, our
      respondents give medical interventions for children (independent from the medical
      sector) a higher priority. Mit vorang. Satz weicht die engl. Zusammenfassung von
      der dt. Zusammenfassung ab Apart from this it is obvious that interventions with
      controversial effectivity should not be covered by the health insurance companies
      to the same extent as those with established effectivity, which is, in a way, in
      contrast to valid German legal regulations.

PMID- 11441674
TI  - [Relevance and financing of health services: a survey of physicians, students,
      patients, nursing personnel and seniors].
AB  - BACKGROUND: In Germany public opinion is increasingly in favour of being included
      in decisions on priority and rationalisation of health care, as practiced in
      other countries for years. One question is, which influence medical know-how and
      patients' experience have on the assessment of health services (importance or
      reimbursement of expenses). In addition to a representative survey it would be
      appropriate to include certain groups like physicians, medical students, nursing
      staff, patients and inhabitants of old people's homes in a relevant survey.
      DESIGN: We conducted a survey of six groups, differing in medical know-how,
      personal affliction and age, by a highly standardized questionnaire. The group of
      physicians received the questionnaire by mail with one reminder. The
      questionnaire was handed out to the other groups (directly). SETTING: 150
      practices of internal specialists and general practitioners in and around Lubeck,
      a preclinical and a clinical semester of the Medical University of Lubeck, an old
      people's home in Lubeck-Travemunde and a cardiological clinic for rehabilitation
      in Bad Segeberg. SUBJECTS: 150 practising physicians (internal specialists,
      general practitioners), 100 medical students of a preclinical semester and
      another 100 of the fifth clinical semester, 100 patients in cardiological
      consulting hours in a cardiological clinic, 100 members of the nursing staff of
      the same clinic and 110 residents in an old people's home. The survey period was
      between December 1997 and February 1998. INSTRUMENT: The questionnaire was
      identical to a parallel public survey. On the one hand defined health services
      were assessed in respect of importance and reimbursement of expenses. On the
      other hand, more general questions were asked regarding possible ways of
      financing or economization in public health. RESULTS: A response rate of 82% was
      achieved in the group of inhabitants of the old people's home. Doctors and
      students showed a response rate between 60% and 70%, while the response rate of
      patients and nursing staff was about 50%. A clear agreement between groups could
      be found in the evaluation of health services in the case of severe illnesses of
      children, which achieved the highest rating. The evaluation of health services of
      controversial effectivity like homoeopathic drugs or acupuncture varied most.
      There was a tendency in the patients' group to rate the importance of the listed
      health services higher than in the other groups, especially doctors and clinical
      students. All groups showed readiness to assign more financial consequences to
      patients with illnesses caused by the patient's behaviour, e.g. dangerous forms
      of sports or smoking. CONCLUSION: Laity as well as experts showed a distinct
      interest in the complex subject. Medical know-how goes along with a more critical
      evaluation of the importance of numerous indications. Patients distinguished less
      between different health services. The questionnaire showed that those directly
      concerned wish to be included in the discussion and feel that decisions
      concerning priority-setting in public health should not be left to politicians
      and health insurance companies alone.

PMID- 11441675
TI  - [Malaria incidence in Germany 1998/99--results of single case studies of the
      Robert Koch Institute].
AB  - Malaria is a common imported infectious disease in Germany. A total of 931 cases
      of malaria were reported in Germany in 1999 (1998: 1,008 cases). Most of the
      infected patients were 24-45 years of age. Eighty per cent of the cases acquired
      infection in Africa, in Asia (8.5%) and in Central and South America (5%).
      Plasmodium falciparum accounted for the largest number of cases (80%) followed by
      Plasmodium vivax (12%). In 1999 60% of all malaria cases were Germans. Most of
      them travelled for holidays or study purposes. 20 deaths, all attributed to
      falciparum malaria, were notified in 1999, most of them (19) were German
      citizens. In 1999 61% of the patients had not taken chemoprophylaxis at all while
      travelling abroad. Improving prophylactic measures is the only way to reduce the
      incidence of malaria cases in Germany.

PMID- 11441676
TI  - [Legionellas in domestic warm water--effects on the health of residents].
AB  - Only few epidemiological data on legionella diseases are available in Germany and
      studies on the prevalence of legionella antibody response in the population are
      scarce. We report on an epidemiological study on immune response in residents of
      homes with heavy and with minor legionella contamination in their hot-water
      system. 53 inhabitants of houseblocks with central hot-water system and high
      legionella contamination (6,049 +/- 17,995 cfu/l; 40% > 1,000 cfu/l) were
      studied. 92 persons living in 1-2 family houses with decentral hot water systems
      (244 +/- 1,434 cfu/l; 3% > 1,000 cfu/l) served as controls. All persons filled in
      a questionnaire on bronchial and fever diseases etc; blood specimen were tested
      for legionella antibodies (different methods: immunofluorescence, and ELISA), and
      urine specimens were analysed for legionella antigen. During this investigation
      in the population exposed to Legionella no cases of legionellosis were reported.
      The prevalence of legionella antibodies was twice as high in the exposed versus
      the control persons. Significant correlation between cfu/l and legionella
      antibody titer in the inhabitants were found. One person with high antibody titer
      and with legionella-free hot-water system in his home had reported about
      pulmonary problems after having stayed in a hotel. The positive antibodies of the
      other persons are most likely the result of asymptomatic infections caused by
      permanent exposure in their home hot-water supply. In conclusion, with regard to
      the increased prevalence of antibody titers against legionellae in the exposed
      inhabitants and the significant correlation between antibody titers and cfu/l in
      hot-water samples, the necessity to control and redevelop hot-water systems in
      homes is confirmed--even though no cases of legionelloses in the exposed
      population were reported.

PMID- 11441677
TI  - [Accidents in preschool children in the Boblingen district--accident causes and
      risk groups].
AB  - The characteristics of childhood accidents including their socio-demographic
      distribution were analysed using a cross-sectional design. In December 1999,
      questionnaires were sent to 50 kindergartens in the 'Landkreis Boblingen'
      (Southern Germany). 2,963 children went to these kindergartens, and the parents
      of the children were asked to fill in the questionnaire which was then analysed
      anonymously by the local health authority of Boblingen. The parents of 1,866
      children sent back the questionnaire; the response rate was 72.0% for children
      with German nationality and 31.6% for the other children. On the average the
      parents reported 26 'accidents leading to a physician contact' per 100 child-life
      years. Four indicators were used for characterising the socio-economic status of
      the parents (per capita income, occupational status of the father, school
      education of the mother, summary index), and three groups (low, medium and high
      socio-economic status) were constructed with each including about 1/3 of the
      children. Children from the low status group had about 13% fewer accidents than
      children from the high status group; for severe accidents, however, a contrary
      association was found (OR of the low as compared with the high status group: 4.1;
      Conf. Inter.: 1.12-14.96). The children with another nationality than German had
      severe accidents more often than German children (OR: 4.63; Conf. Inter.: 2.24
      9.52). Boys had 33% more accidents than girls. About 3/4 of all accidents took
      place at home or in its direct environment. Concerning the age distribution, a
      peak was seen at age 2. The following accidents occurred particularly often:
      falling from stairs (10.2% of the accidents), falling from a playground equipment
      (9.5%), falling from a bicycle (8.9%), falling from a high bed (6.0%), stabs or
      cuts (4.9%), burns or scalds (4.4%), falling from a high chair (3.9%), falling
      from a nursery table (3.2%). The results are used by a regional working group
      which is asked to develop a strategy aimed at reducing accidents of pre-school
      children in the 'Landkreis Boblingen' until 2006 by 10%.

PMID- 11441678
TI  - Prevalence of metronidazole-resistant Trichomonas vaginalis in a gynecology
      clinic.
AB  - OBJECTIVE: To determine the prevalence of in vitro resistance to metronidazole
      among unselected isolates of Trichomonas vaginalis and correlate in vitro
      findings with response to metronidazole therapy. STUDY DESIGN: Vaginal fluid from
      women attending a gynecology clinic at an urban hospital was cultured, isolates
      were tested for in vitro resistance to metronidazole, and these results were
      correlated with therapeutic outcome. RESULTS: Among 911 women, T vaginalis was
      detected by culture in 82 (9.0%). Of the 82 isolates, 2 (2.4%; 95% CI, 0.3-8.5%)
      had low-level in vitro resistance (minimum lethal concentration, 50
      micrograms/mL). Women with positive wet mount examinations were treated with
      metronidazole, 2 g, once and asked to return in one week. Of the 42 infected
      women agreeing to return for a repeat examination and culture, 26 (61.9%) did,
      and all (including one woman with a resistant isolate) were cured. CONCLUSION:
      Isolates of T vaginalis resistant to metronidazole occur widely throughout the
      United States. Although the in vitro susceptibility of T vaginalis to
      metronidazole has been very poorly studied, our study is consistent with a decade
      old prevalence estimate of in vitro resistance (5%), and suggests that high-level
      resistance is uncommon. This study confirmed, in the absence of reinfection, the
      continuing clinical effectiveness of single-dose metronidazole for the large
      majority of trichomoniasis cases.

PMID- 11441679
TI  - Maternal race/ethnicity and twinning rates in the United States, 1989-1991.
AB  - OBJECTIVE: To utilize United States birth certificate data (years 1989-1991) to
      examine the effects of race/ethnicity on twinning rates. STUDY DESIGN: We used a
      database of birth certificate data for the United States (years 1989-1991)
      available on CD-ROM from the United States National Center for Health Statistics.
      This linked birth/infant death data set included a total of 12,036,234 birth
      records, of which 279,073 were twins. Excluded from the analysis were 15,086 twin
      birth records (5.4%) based upon previously described exclusion criteria.
      Statistical analysis included a series of univariate analyses to determine the
      rates of twinning between different racial/ethnic groups correlated with maternal
      age, education, marital status and place of birth. Comparisons were analyzed
      using the chi 2 test, with significance at P < .05. RESULTS: The overall twinning
      rate was 2.26%, with the lowest rate observed in the group denoted non-Hispanic
      other (1.67%) and highest among non-Hispanic blacks (2.69%). Twinning rates
      within various groups representing Hispanics ranged from 1.76% to 2.08%. The
      twinning rate was significantly higher among U.S.-born as compared to non-U.S.
      born women (2.34% vs. 1.88%, P < .005) except for Puerto Ricans, Cubans and
      Central/South Americans, for whom the reverse was true. Women aged 35-39 had the
      highest twinning rate (3.05%), whereas women aged 15-19 had the lowest; that
      trend persisted in all racial/ethnic groups. The study showed a nonsignificant
      relationship between marital status or education and twinning rate. CONCLUSION:
      Race/ethnicity studies can be useful in designing programs that may maximize
      health outcomes of twins in a racially diverse population.

PMID- 11441680
TI  - Microwave endometrial ablation at a frequency of 2.45 GHz. A pilot study.
AB  - OBJECTIVE: To investigate the clinical application of a microwave tissue
      coagulator at 2.45 GHz with a needle electrode customized for endometrial
      ablation. STUDY DESIGN: In a pilot clinical study, endometrial ablation was
      performed under intravenous thiopental anesthesia on five women suffering from
      hypermenorrhea caused by aplastic anemia (3), von Willebrand's disease (1) and a
      submucosal myoma (1) using a microwave tissue coagulator at 2.45 GHz. RESULTS:
      Four patients were amenorrheic after endometrial ablation. The patient with the
      submucosal myoma experienced minor menstrual bleeding. No notable complications
      were observed during or after ablation. CONCLUSION: Endometrial ablation using a
      microwave tissue coagulator at 2.45 GHz is a simple and useful method of treating
      hypermenorrhea.

PMID- 11441681
TI  - A comparative study of raw and prepared semen samples from two consecutive days.
AB  - OBJECTIVE: To study and compare raw and prepared semen samples from two
      consecutive days by conventional sperm parameters, various motility
      characteristics of spermatozoa determined by computer-aided sperm analysis and
      calcium ionophore-induced acrosome reaction. STUDY DESIGN: Semen samples of male
      partners in couples undergoing 81 cycles of double intrauterine insemination were
      studied. The first sample was produced after abstinence of 2-7 days and the
      second, 24 hours after the first. Both samples were processed by isolate sperm
      separation medium. RESULTS: Semen volume, sperm concentration and total motile
      spermatozoa were significantly reduced in day 2 raw and prepared samples, whereas
      normal morphology, motility characteristics and percentage of acrosome-reacted
      spermatozoa increased significantly in day 2 inseminated samples as compared to
      day 1. Oligospermic, asthenospermic and teratozoospermic samples showed a
      significant improvement in concentration, various motility characteristics and
      normal morphology of spermatozoa in day 2 samples as compared to day 1.
      CONCLUSION: Men with normal samples showed improvements in normal morphology and
      acrosome-reacted spermatozoa, whereas those with subnormal semen samples from day
      1 showed a significant improvement in concentration, various spermatozoal
      velocities and normal morphology on day 2.

PMID- 11441682
TI  - Microlaparoscopically assisted vaginal hysterectomy. A preliminary report.
AB  - OBJECTIVE: To evaluate the clinical possibility of using a microlaparoscope in
      laparoscopically assisted vaginal hysterectomy. STUDY DESIGN: Twenty-five women
      with different indications for hysterectomy and a uterine size < 14 weeks'
      gestation underwent laparoscopically assisted vaginal hysterectomy using a
      microlaparoscope and 2-mm instruments. RESULTS: Microlaparoscopic procedures
      included coagulation and separation of infundibulopelvic or uteroovarian round
      ligaments, vesico-uterine-visceral peritoneal fold dissection, and anterior and
      posterior colpotomy. The mean operative time, blood loss and length of hospital
      stay were 84.40 +/- 16.85 minutes, 262.00 +/- 112.99 mL and 3.08 +/- 0.64 days,
      respectively. No patients developed serious complications, but there were two
      minor ones. CONCLUSION: Microlaparoscopy appears to be an efficacious alternative
      treatment option in well-selected patients undergoing laparoscopically assisted
      vaginal hysterectomy.

PMID- 11441683
TI  - Sperm parameters in men with suspected infertility. Sperm characteristics, strict
      criteria sperm morphology analysis and hypoosmotic swelling test.
AB  - OBJECTIVE: To determine the distribution of sperm abnormalities in a population
      of suspected infertile men presenting for the initial investigation of male
      factor infertility. STUDY DESIGN: Results obtained in the analysis of sperm
      viability, motility, conventional morphology (including 12 sperm anomalies),
      strict criteria sperm morphology analysis (SCSMA) and hypoosmotic swelling test
      (HOST) were compared in oligozoospermic (< 5.0, 5.1-10.0 and 10.1-20.0 x
      10(6)/mL), normozoospermic (20.1-40.0, 40.1-100.0 and 100.1-250.0 x 10(6)/mL) and
      polyzoospermic (> 250.0 x 10(6)/mL) semen samples from 233 suspected infertile
      men. RESULTS: Percentage of sperm viability, category a and categories a plus b
      of sperm motility, oval-headed sperm, and normal-headed sperm according to SCSMA
      and HOST had a direct relationship with sperm counts (P < .001). Percentage of
      amorphous heads, pinheads, tapering and combined defects showed an inverse
      relationship with sperm counts (P < .001), whereas the percentage of large-headed
      sperm was highest in semen with > 40.0 x 10(6)/mL (P = .003) and of neck/midpiece
      defects was lowest in semen with < 10.0 x 10(6)/mL (P = .03). No significant
      differences were found in the percentage of small heads, double heads, round
      heads, partially elongated heads, cytoplasmic droplet and tail defects. Based on
      the cutoff points established previously for the sperm characteristics analyzed,
      normal values were found in semen with > 250.0 x 10(6)/mL (viability and
      motility), > 100.0 x 10(6)/mL (conventional morphology) and > 40.0 x 10(6)/mL
      (SCSMA and HOST). CONCLUSION: The incidence of defective spermatozoa is lowest in
      semen with the highest sperm count. However, sperm abnormalities that affect male
      fertility may be detected at any level of sperm density. The data indicate that
      an increase in any sperm abnormality should be regarded as a possible cause of
      decreased fertility.

PMID- 11441684
TI  - Features of shoulder dystocia in a busy obstetric unit.
AB  - OBJECTIVE: To assess the incidence and complications of shoulder dystocia and
      whether those complications could be avoided. STUDY DESIGN: Retrospective
      analysis of shoulder dystocia between 1996 and 1999 to determine whether
      macrosomia, diabetes, height of head at full dilatation, length of second stage
      or instrumental delivery could predict shoulder dystocia. Fetal asphyxia,
      brachial plexus injury, maneuvers used to free the shoulders and experience of
      the attendant were also assessed. RESULTS: There were 56 cases of shoulder
      dystocia in 24,000 births, 59% after spontaneous delivery. McRoberts maneuver was
      used in 48 deliveries but sufficed as a solitary procedure in nine cases. The
      addition of suprapubic pressure was sufficient for 25 patients and 27 when
      bilateral episiotomy was also used. Corkscrew procedures were required in 12
      patients. Midwives were involved in 35 cases and required assistance in 27.
      Macrosomia > 4,000 g was a feature in 20 infants and diabetes in 6. Neither the
      height of the head nor the length of the second stage was helpful. There were 13
      cases of Erb's palsy, seven after vacuum delivery and six after spontaneous
      delivery. Eight of these cases were associated with McRoberts procedure and
      suprapubic pressure, two with no procedure and three with the corkscrew
      procedure. CONCLUSION: If all infants > 4,000 g had been delivered by cesarean
      section, there still would have been 36 cases of shoulder dystocia. If the
      ultrasonically estimated weight were used to select patients for cesarean
      section, seven cases would have been diagnosed. To lessen the degree and
      incidence of fetal injury, labor ward staff are urged to become as familiar as
      possible with the techniques of freeing the shoulders.

PMID- 11441685
TI  - Amniotic fluid index in the uncomplicated term pregnancy. Prediction of outcome.
AB  - OBJECTIVE: To establish whether an association between oligohydramnios and
      pregnancy outcome is present in the uncomplicated term pregnancy. STUDY DESIGN:
      Pregnancies with a singleton fetus in cephalic presentation at term (> or = 37
      weeks), a reactive non-stress test and an antepartum amniotic fluid index
      performed within four days of delivery between January 1994 and September 1998
      were identified. Excluded were those with any maternal or fetal complication or
      unavailable outcome information. The primary outcome measure was rate of
      operative vaginal or abdominal delivery for a nonreassuring fetal heart rate
      tracing. Statistical analysis included Fisher's exact test and one-way analysis
      of variance, with a two-tailed P < .05 considered significant. RESULTS: Two
      hundred thirty-two women met the inclusion criteria; of them, 44 (19%) had an
      amniotic fluid index < or = 5 cm. There was no difference in the operative
      delivery rate for a nonreassuring fetal heart tracing between those with a normal
      amniotic fluid index > 5 cm vs. < or = 5 cm (39 [21%] vs. 5 [11%], P > .05). In
      addition, there were no differences between the two groups in rates of neonatal
      intensive care unit admissions or five-minute Apgar scores < 7. Patients with a
      normal amniotic fluid index had a significantly lower labor induction rate (96
      [51%] vs. 42 [98%], P < .001) and higher rate of meconium-stained amniotic fluid
      (65 [35%] vs. 7 [16%], P = .01) than those with a low amniotic fluid index.
      CONCLUSION: In the uncomplicated pregnancy at term, an amniotic fluid index < or
      = 5 cm increases the incidence of labor induction but does not appear to affect
      the rate of operative delivery for abnormal fetal heart rate tracings.

PMID- 11441686
TI  - Psychosexual aspects of vulvar vestibulitis.
AB  - OBJECTIVE: To explore the psychological, interpersonal and sexual correlates of
      vulvar vestibulitis via qualitative and quantitative analysis. STUDY DESIGN:
      Sixty-nine women diagnosed with vestibulitis were recruited from a vulvar/vaginal
      disease clinic to complete a comprehensive quantitative and qualitative
      questionnaire designed to assess general health concerns, mental health, sexual
      functioning and interpersonal relationships. RESULTS: The majority of
      participants reported drastic changes in sexuality associated with the onset of
      vestibulitis. Upon developing vestibulitis, 88% reported decreased interest in
      sexual activity, 87% indicated that they were less willing to participate in
      sexual activity, and 94% maintained that they were less able to participate in
      sexual activity. High levels of frustration and symptoms of depression also were
      frequently reported. CONCLUSION: Vulvar vestibulitis is associated with
      significant changes in sexuality, intimate relationships and psychological well
      being. When treating women with vestibulitis, medical professionals should
      consider the psychological and sexual aspects of the disease in addition to
      physical concerns.

PMID- 11441687
TI  - Outpatient cervical ripening using a sustained-release prostaglandin E2 vaginal
      insert.
AB  - This clinical trial was undertaken to determine whether a sustained-release
      prostaglandin E2 vaginal insert could be used for outpatient cervical ripening. A
      total of 111 patients, with primarily pregnancy-induced hypertension or
      postdatism, were administered the insert in a simulated outpatient setting. The
      high rates of regular contractions (23.4%) and of removal of the insert before <
      12 hours (27.9%) make its use undesirable outside a hospital.

PMID- 11441688
TI  - Placenta increta/percreta associated with uterine perforation during therapy for
      fetal death. A case report.
AB  - BACKGROUND: Placenta accreta involves abnormal adherence of the placenta to the
      myometrium. Placenta increta and percreta are defined by the degree of
      trophoblastic penetration of the myometrium. These conditions are rarely observed
      in the first trimester; placenta increta and percreta are exceptionally
      infrequent. CASE: A woman had a uterine perforation after suction curettage for
      fetal death at 11 weeks' gestation, requiring hysterectomy for control of a
      profuse hemorrhage. Histopathologic examination of the uterus revealed placenta
      increta involving the lower uterine segment and placenta percreta at the site of
      uterine perforation. CONCLUSION: This is the first report of placenta percreta
      associated with uterine perforation during therapy for first-trimester fetal
      death.

PMID- 11441689
TI  - Cerebral abscess and thrombophilia in pregnancy. A case report.
AB  - BACKGROUND: Cerebral abscess in pregnancy is a rare event, with the etiology not
      well described. We present such a case in association with genetic thrombophilia.
      CASE: A 36-year-old primigravida with a prior history of bilateral popliteal vein
      thrombosis and pulmonary embolism presented in early gestation with right
      hemiparesis, aphasia, disseminated intravascular coagulation and a space
      occupying lesion in the left temporal lobe. Stereotactic biopsy confirmed the
      presence of an abscess. The patient also had a homozygous methylene
      tetrahydrofolate reductase mutation (C677T), protein S deficiency and lupus
      anticoagulant, all of which possibly contributed to the thrombosis, infarct,
      infection and abscess. She was successfully treated with low-molecular-weight
      heparin and antibiotics and had a term vaginal delivery. CONCLUSION: Recently
      genetic thrombophilia was reported in association with various complications of
      pregnancy, but it has never before been described as occurring with a cerebral
      abscess.

PMID- 11441690
TI  - Leiomyosarcoma of the vulva. A case report.
AB  - BACKGROUND: Leiomyosarcoma of the vulva is a rare mesenchymal tumor. Biologic
      features of a low grade tumor were investigated by an immunohistochemical workup.
      CASE: A 38-year-old woman presented with a slowly growing vulvar mass. Surgical
      treatment was performed, and a low grade leiomyosarcoma of the vulva was
      diagnosed. Immunohistochemical reactions were performed with monoclonal
      antibodies against desmin, vimentin, smooth muscle actin, cytokeratin, S-100
      protein, estrogen, progesterone and androgen receptor, p53 protein, Ki-67
      antigen, leukocyte common antigen and polyclonal antibodies to factor VIII
      related antigen. Expression of estrogen, progesterone and androgen receptor was
      present in addition to a moderate number of Ki-67-positive cells and absence of
      p53 protein overexpression and lymphatic cell infiltration besides adequate
      microvessel density for smooth muscle tumors. Since the immunohistochemical
      markers indicated a less aggressive tumor, any further adjuvant therapy was
      rejected. The patient was without recurrence 24 months later. CONCLUSION: The
      immunohistologic profile proved the low histologic grade of vulvar
      leiomyosarcoma. The findings helped to estimate prognosis and plan therapy.

PMID- 11441691
TI  - Septate uterus with double cervix and longitudinal vaginal septum. A case report.
AB  - BACKGROUND: Congenital uterine anomalies in the general population are estimated
      to have an incidence of 0.001-10%. The septate uterus, the most common form of
      structural uterine anomaly, has the highest reproductive failure rate. A rare
      developmental variant is a septate uterus with cervical duplication and a
      complete longitudinal vaginal septum. The existence of this anomaly challenges
      classical mullerian developmental theory. Traditional transabdominal metroplasty
      has been replaced by operative hysteroscopy in the surgical correction of a
      septate uterus, with laparoscopy aiding in the diagnosis and contributing to the
      safety and efficiency of the procedure. CASE: A 28-year-old, nulliparous woman
      with a septate uterus with cervical duplication and complete longitudinal vaginal
      septum was diagnosed by combined laparoscopy and hysteroscopy. Excision of the
      complete longitudinal vaginal septum followed by hysteroscopic partial resection
      of a thick uterine septum with laparoscopic assistance was performed. However,
      because of the septum's broad base and the rigidity of the operative
      resectoscope, we opted to proceed with transabdominal metroplasty. CONCLUSION:
      Only six cases of septate uterus with cervical duplication and complete
      longitudinal vaginal septum have been reported. Although its counterpart, the
      septate uterus, has effects on preterm labor, fetal presentation, infertility and
      spontaneous abortion, its reproductive outcome has not been assessed. Review of
      the literature suggests that surgical correction in the setting of poor
      reproductive outcome has been beneficial. Laparoscopically assisted hysteroscopic
      resection of the uterine septum is a safe, effective surgical technique of
      uterine reunification and is preferable to transabdominal methods. However, in
      certain cases, conventional transabdominal metroplasty may still be required.

PMID- 11441692
TI  - Unilateral deep vein thrombosis associated with a large myoma uteri. A case
      report.
AB  - BACKGROUND: Deep vein thrombosis is a rare complication of myoma uteri. There
      have been few reports on this association. CASE: A 42-year-old woman presented
      with a myoma uteri, 24 weeks in size, that had compressed the pelvic veins and
      caused unilateral deep vein thrombosis of the left leg. After anticoagulation
      therapy, a total abdominal hysterectomy was performed, with an uneventful
      recovery. CONCLUSION: Although deep vein thrombosis associated with myoma uteri
      is a rare event, it can be managed successfully with anticoagulants and
      hysterectomy. Myoma uteri with deep vein thrombosis is an indication for
      hysterectomy.

PMID- 11441693
TI  - [Protection against biting mosquitoes].
AB  - The protection against arthropods especially disease transmitting mosquitoes is
      becoming more and more important. The problems with drugs used for treatment and
      prophylactic of malaria are rapidly growing due to emergence of resistant
      parasites and unwanted side effects. Furthermore the population living in endemic
      area often can't afford the new expensive drugs. A safe and effective way of
      preventing insect bites is needed. One can prevent arthropod born diseases by
      avoiding insect bites through physical and chemical means or a combination of
      both. Repellents are substances applied to the skin, which effectively prevent
      insects from biting. The gold standard is still Diethylbenzamine (DEET), which is
      highly effective, well documented and in use for more than 50 years. The new
      repellent Bayrepel (hydroxyethyl isobutyl piperidin carboxylate) available to the
      consumer since 1998, seems to have an efficacy comparable with DEET. Insecticides
      have a direct toxic effect on the nervous system of arthropods. Mainly synthetic
      pyrethroids, which produce less ecological problems than the older products, are
      used. They are supplied in form of sprays, vaporising mats or coils. An important
      progress is the combination of insecticides with physical means. Insecticide
      treated bed nets or clothes give an excellent protection. Topical or systemic
      Vitamin B1, acoustic devices and electrocuters are still sold and widely used
      although their complete ineffectivity is documented in many studies.

PMID- 11441694
TI  - [Malaria--chemoprophylaxis 2001].
AB  - An estimated 20,000 to 30,000 cases of imported malaria are annually diagnosed in
      industrialised countries. Some 700 of them concern Swiss travellers and foreign
      guests. Exposure prophylaxis and chemoprophylaxis for high risk destinations
      lower the risk of malarial disease. The latter is defined as regular intake of
      antimalarial drugs in subtherapeutic dosage in order to suppress the development
      of clinical disease. Drugs are usually taken from one week before travel until
      four weeks after return from an endemic area. Mefloquine, doxycycline,
      chloroquine plus proguanil, and presumably soon also atovaquone plus proguanil
      are available in Switzerland for chemoprophylaxis.

PMID- 11441695
TI  - [Malaria--rapid diagnostic tests and emergency self-medication].
AB  - WHO recommendations have adopted the option of stand-by emergency treatment (SBT)
      for travellers to areas where malaria is endemic and medical attention may not be
      obtained within 24 hours after onset of symptoms. Indication and choice of drugs
      for SBT depend on use and kind of a chemoprophylactic regimen, situation of
      plasmodial resistance at the destination, and contraindications and tolerability
      in the individual traveller. However, the diagnosis of malaria on clinical
      grounds alone is unreliable, and fever occurs frequently during travel to malaria
      endemic areas from various reasons. The possibility of malaria has to be
      considered in all cases of unexplained fever that starts after the 7th day of
      stay in an endemic area. Studies in European travellers have shown that only 0.5
      1.4% of all travellers to whom SBT medication has been prescribed, will finally
      use it. SBT use in febrile travellers (8.1-10.4% of all travellers) has been 4.9
      17%, but plasmodial infection could be confirmed retrospectively in 10.8-16.7% of
      SBT-users only. The recent introduction of rapid diagnostic tests (RDT) for
      malaria has provided a potential tool to self-diagnose and treat a possible
      malaria attack when medical attention or microscopic diagnosis is not available.
      However, the utilisation of currently available RTDs by travellers has been shown
      to be technically problematic. Healthy volunteers were able to learn how to
      perform the tests, especially when standard written instructions were
      supplemented with verbal information (75 vs. 90% successful performance). But
      their interpretation of test results was unsatisfactory, with a high rate of
      false-negatives (14.1%). In another study in febrile European tourists in Kenya,
      only 68% of patients were able to perform the RDTs correctly, and 10 out of 11
      with microscopically confirmed malaria failed to diagnose themselves accurately.
      Thus, besides appropriate training before departure, technical improvements are
      required before such RDT kits can be recommended for self-use by travellers.

PMID- 11441696
TI  - [Vaccinations for overseas travelers--new evidence and recommendations].
AB  - Vaccinations are an easy and highly effective way to keep travellers healthy.
      There are few problems with compliance, as all vaccinations are administered
      pretravel and many vaccines offer protection rates > 95% after a single dose
      (e.g. hepatitis A, yellow fever). Vaccination of hepatitis A and
      diphtheriatetanus are recommended for all developing countries. Polio is still
      indicated for Asia and Africa. Hepatitis B, if possible in combination with A, is
      recommended for persons travelling for > 30 days, travellers < 35 years, and for
      people showing special risk behaviour (e.g. high-risk sports, unprotected sexual
      intercourse). Depending on destination and kind and duration of travel, further
      vaccinations have to be considered, e.g.: yellow fever (endemic areas, rule of
      entry), rabies (trekking, travel in remote areas), typhoid fever (Indian sub
      continent), meningococcal meningitis (meningitis belt, pilgrims to Saudi-Arabia),
      tick-borne encephalitis (endemic areas in Europe and Asia), influenza (persons at
      special risk of complications), Japanese encephalitis (low standard travel in
      rural areas of Southeast Asia > 30 days), measles (particularly endemic in
      Africa). Cholera vaccination is virtually never indicated. Several vaccines can
      be delivered at the same time.

PMID- 11441697
TI  - [Travelers' diarrhea].
AB  - Diarrhea is the most common health problem of travelers to tropical destinations,
      affecting up to over 50%, with however considerable regional and seasonal
      variation. Orally acquired bacterial pathogens, particularly enterotoxigenic
      Escherichia coli, are the most frequent etiology of travelers' diarrhea occurring
      during the first three weeks of travel. Protozoal infections, e.g. giardia and
      Entamoeba histolytica, are more often the cause of diarrhea and prolonged
      problems of intestinal motility of the returning traveler--as are postinfectious
      irritable bowel syndromes. Prevention seems theoretically simple by avoiding any
      potentially contaminated food and drinks, but the principle of 'cook it, boil it,
      peel it, or avoid it is obviously a goal difficult to achieve. Several
      antibiotics have shown to be able to prevent diarrhea for a short period of time,
      but the potential of adverse effects and selection of resistant pathogens calls
      for a restrictive use for short trips of particularly vulnerable subjects only.
      The use of probiotics--e.g. Saccharomyces boulardi, Streptococcus faecium--gave
      conflicting results--both in prevention and treatment. The basics of treatment is
      appropriate fluid replacement--mostly by the oral route. Although this measure
      can safely bridge the time until spontaneous remission, it fails to reduce the
      duration of illness. Appropriate antibiotics are fairly effective to reduce the
      duration of travelers' diarrhea, especially if combined with loperamid. The
      administration of the later is contraindicated in small children. The most
      commonly used and well documented antibiotics belong to the fluoroquinolones.
      Alternatives for pediatric use are azithromycin and cotrimoxazole. Considering
      the mostly short duration of travelers' diarrhea the administration of
      antibiotics can be limited to cases of acute febrile dysentery and violent
      diarrhea when rapid relief is essential. In cases of febrile diarrhea malaria
      must be considered if the patient has been exposed to the risk of transmission.

PMID- 11441698
TI  - [Travel with small children].
AB  - Travelling with young children can lead to difficult situations. Accordingly,
      travel preparations should be geared towards the needs of the youngest with
      appropriate medical advise. Young children tolerate most means of transportation.
      When travelling long distances by car, clear rules ought to be established, and
      many children require antiemetic measures. With regards to traffic safety,
      compromises during family vacation are not acceptable. Travelling by plane or
      train is less stressful than travelling by bus or car. As a medical advisor, one
      ought to be familiar with age limits for certain immunizations and medications
      (particularly antimalarial agents). Parental knowledge of modern rules for oral
      rehydration in cases of traveller's diarrhoea is frequently insufficient.
      Whenever possible, travelling with young children to high risk regions should be
      avoided.

PMID- 11441699
TI  - [First aid kit for travelers].
AB  - The first aid kit for travellers is essentially thought to permit symptomatic
      self-treatment of common and mostly trivial health problems abroad. If
      professional medical assistance is likely not to be accessible a few additional
      items--e.g. an antibiotic--must be considered. The indications and proper
      handling of any medication which requires a physician's prescription have to be
      carefully explained to its potential user. The decision as to recommend drugs
      other than those in the basic first aid kit must take into account not only the
      risk of particular diseases but also the ability of the traveller to applicate a
      drug in the correct way for defined indications.

PMID- 11441700
TI  - [Travel medicine for HIV-infected patients].
AB  - Many HIV-infected persons travel from temperate zones to (sub)tropical
      destinations. HIV-specific immigration issues, medical resources abroad and
      problems regarding travelling with multiple medications have to be anticipated.
      When prescribing immunizations and specific chemoprophylaxis, the stage of
      immunodeficiency as well as drug interactions with antiretrovirals and
      medicaments against opportunistic infections have to be taken into account. Live
      vaccines may be contraindicated. Immunocompromised HIV-infected travellers have a
      higher risk for serious courses of diseases by enteropathogens. Therefore a good
      information about food hygiene is important and a prescription of an antibiotic
      to take in case of severe diarrhea may be indicated. A new antiretroviral
      combination therapy should not be started immediately before travelling to the
      tropics. The possibility to continue an established HIV treatment during travel
      has to be evaluated cautiously. With good pre-travel advice the risk of severe
      health problems is low for most HIV-infected travellers.

PMID- 11441701
TI  - [Mountaineering and altitude sickness].
AB  - Almost every second trekker or climber develops two to three symptoms of the high
      altitude illness after a rapid ascent (> 300 m/day) to an altitude above 4000 m.
      We distinguish two forms of high altitude illness, a cerebral form called acute
      mountain sickness and a pulmonary form called high altitude pulmonary edema.
      Essentially, acute mountain sickness is self-limiting and benign. Its symptoms
      are mild to moderate headache, loss of appetite, nausea, dizziness and insomnia.
      Nausea rarely progresses to vomiting, but if it does, this may anticipate a
      progression of the disease into the severe form of acute mountain sickness,
      called high altitude cerebral edema. Symptoms and signs of high altitude cerebral
      edema are severe headache, which is not relieved by acetaminophen, loss of
      movement coordination, ataxia and mental deterioration ending in coma. The
      mechanisms leading to acute mountain sickness are not very well understood; the
      loss of cerebral autoregulation and a vasogenic type of cerebral edema are being
      discussed. High altitude pulmonary edema presents in roughly twenty percent of
      the cases with mild symptoms of acute mountain sickness or even without any
      symptoms at all. Symptoms associated with high altitude pulmonary edema are
      incapacitating fatigue, chest tightness, dyspnoe at the minimal effort that
      advances to dyspnoe at rest and orthopnoe, and a dry non-productive cough that
      progresses to cough with pink frothy sputum due to hemoptysis. The hallmark of
      high altitude pulmonary edema is an exaggerated hypoxic pulmonary
      vasoconstriction. Successful prophylaxis and treatment of high altitude pulmonary
      edema using nifedipine, a pulmonary vasodilator, indicates that pulmonary
      hypertension is crucial for the development of high altitude pulmonary edema. The
      primary treatment of high altitude illness consists in improving hypoxemia and
      acclimatization. For prophylaxis a slow ascent at a rate of 300 m/day is
      recommended, if symptoms persist, acetazolamide at a dose of 500 mg/day is
      effective. Mild acute mountain sickness may also be treated with the same dose
      acetazolamide. Glucocorticoids are the first line treatment of the malignant form
      of acute mountain sickness. Nifedipine is effective only for the prophylaxis and
      treatment of high altitude pulmonary edema.

PMID- 11441702
TI  - [Poisonous snake bites: prevention--first aid--clinical management].
AB  - Envenomation due to terrestrial snakes is a rarity in travellers and tourists and
      can be readily controlled by preventive measures. It is a widely underestimated
      health problem of the rural population in tropical and subtropical countries,
      however. Prevention, First Aid, diagnostic procedures, symptomatic and specific
      (antivenom) treatment regimens of envenomation due to terrestrial snakes are
      presented.

PMID- 11441703
TI  - [Air travel--a disease risk? ].
AB  - Civil air traffic moves in an altitude that is dangerous for human beings without
      technical aids. Low temperature and humidity, reduced air pressure combined with
      oxygen pressure, seasonal depending high concentration of ozone and cosmic
      radiation may also be risk factors. Further risks on long haul flights may be jet
      lag, risk of economy class syndrome and contact with permethrin, because of
      disinsection before take-off out of tropical regions. The aim of an airline is to
      offer good cabin air quality, comfort and security for all passengers, may they
      be healthy, old, disabled or sick. Medical incidences on board arise and
      passengers expect modern equipment such as doctor's kit and defibrillators.

PMID- 11441704
TI  - [Clinical evidence].

PMID- 11441705
TI  - [Referral pattern of the heart catheterization laboratory at the Bern Island
      University Hospital].
AB  - Coronary angiography is a common diagnostic procedure to identify patients with
      coronary artery disease who need to undergo revascularization. It is expensive,
      carries a certain risk and must therefore be thoroughly scrutinized. An expert
      panel evaluated the indication criteria (Swiss Guidelines) to serve as a decision
      basis for the work-up of patients. The presented data acquisition considers the
      pathway of assignment as well as demographic data in addition to these criteria.
      A total of 2369 patients were referred to the cardiac catheterization laboratory
      of the University Hospital of Berne in 1996. Of these, 504 (21%) were randomly
      analyzed retrospectively. The selection consisted of the first 84 patients every
      second month. For 90% of these patients, the Swiss Guidelines attested an
      appropriate indication. The majority of the remaining 10% of the patients showed
      an appropriate indication as well which, however, had not been included into the
      Swiss Guidelines. Compared with other studies it is of note that one third of the
      patients underwent no prior stress test. In contrast, in a similar study in
      Frankfurt three quarters of the patients had a stress test to assess the chest
      pain before angiography. An increased percentage of patients with a previous
      coronary angioplasty was found in Berne. It may reflect the more recent period of
      data collection. The data represent a valid impression of the patient mix of the
      cardiac catheterization laboratory at the University Hospital of Berne. The
      indications for coronary angiography were found to be appropriate in virtually
      all cases. Demographic variables and procedure results are in keeping with
      comparable studies.

PMID- 11441706
TI  - [Employment and communication of hearing disabled patients].
AB  - Communicative disorders can remain an uncomfortable, costly, and debilitating
      factor throughout the lives of millions of children and adults. Deafness is a
      common problem and no age group is spared. Causes of hearing loss are numerous,
      and may be multifactorial in an individual. Important causes include trauma,
      including noise and air pressure changes; genetic hearing loss; infection,
      including rubella; drug damage, metabolic and neoplasia. Prompt detection and
      management of hearing loss in children is essential to ensure adequate
      development of language and associated skills. Untreated hearing loss in adults
      may cause them to withdraw from social activities. The patient with a hearing
      loss may represent difficult evaluation and management decisions. While
      individuals with defective hearing have a wide-ranging choice among absolutely
      attractive occupations, that choice is likely to be narrowed along with growing
      severity of the handicap. Hazardous, hearing-related, contact, and noisy
      occupations are not suitable for them. In handling such persons, due
      consideration should be given not only to the handicap proper but very much also
      to psychological aspects.

PMID- 11441707
TI  - [Antibiotic resistance in respiratory tract infections: what can we do?].
AB  - The emergence of resistant bacteria is a worldwide problem. The knowledge about
      the local situation of resistant bacteria, the mechanisms of resistance and the
      judicious use of antibiotics may reduce the spread of resistant bacteria.

PMID- 11441708
TI  - [Sudden left-sided vision loss. Occlusion of the left central retinal artery].
AB  - A 77 year old female patient was admitted to our hospital because of a rapid
      onset left-sided visual loss. Occlusion of the left central retinal artery was
      confirmed by the consultant ophthalmologist. The patient was further evaluated to
      exclude a thromboembolic event. Chest x-ray was consistent with pulmonary
      hypertension. Doppler echocardiography revealed a secundum atrial septal defect
      with a bi-directional shunt. In this 77 year old patient, arterio-arterial
      embolism from atherosclerotic plaques is the most probable cause of her central
      retinal artery occlusion. Yet, paradoxical embolism might be another reason for
      acute visual loss in this setting, which, however, is difficult to confirm
      definitively.

PMID- 11441709
TI  - [Acquired C1-esterase inhibitor deficiency with angioedema in lymphoplasmocytic
      lymphoma].

PMID- 11441710
TI  - [Cicatricial alopecia of the neck in an African. Nuchal keloid acne].

PMID- 11441711
TI  - [Oral medicine].
AB  - Oral medicine is the discipline in dentistry which deals with diagnosis and non
      surgical treatment of lesions and diseases of the oral tissues, particularly
      those of a systemic, multiorgan or drug-induced nature. In the Netherlands, the
      oral and maxillofacial surgeon is usually the one who takes care of oral
      medicine. In the dental curriculum in the Netherlands oral medicine is not taught
      as a separate discipline, but is included in the courses of oral and
      maxillofacial surgery, oral pathology, periodontology and also, amongst others,
      in the course of biochemistry. In the Netherlands it is not a recognised
      speciality and it is questionable whether there really is a need for it. In the
      medical curriculum and in the training program for family doctors only a very few
      hours on oral diseases is included. Since many patients with oral diseases see
      their family doctor first, an extension of the numbers of hours on oral diseases
      in general and, more specific, in oral medicine, in the medical curriculum is
      recommended.

PMID- 11441712
TI  - [Interaction between dentists, general practitioner and medical specialist].
AB  - Dentists and oral hygienists experience nowadays more frequently the need for
      special (medical) care for their patients. After consulting the family doctor or
      medical specialist the dental treatment must often be modified to fit the
      patient's general condition. The dental professional asks in these circumstances
      for expertise; in the field of oral medicine the dentist is the expert for the
      family doctor or medical specialist.

PMID- 11441713
TI  - [Diagnosis and therapy of non-odontogenic orofacial infections].
AB  - This article discusses the non-odontogenic inflammations of the oral mucosa,
      connective tissue, bone and temporomandibular joint. Their occurrence, course and
      treatment are related to the patient's immune status, and to microbial and
      environmental factors, as is always the case with infectious processes. The
      article concerns peculiarly several clinical and therapeutic consequences of non
      dontogenic orofacial infections.

PMID- 11441714
TI  - [Vesiculobullous lesions of the oral mucosa].
AB  - In general practice, the dentist can be confronted with a vesiculobullous lesion
      of the oral mucosa. In many cases the lesion can be classified as recurrent
      herpes labialis, but many other causes can induce a vesiculobullous lesion of the
      oral mucosa and perioral skin as well. This article gives an overview of the
      various vesiculous and bullous lesions of the oral mucous membranes. Special
      attention is given to the possible causes and their treatment.

PMID- 11441715
TI  - [Disorders of taste and smell].
AB  - Disorders of taste and smell not only are uncomfortable to the person involved,
      e.g. because of an impaired hedonic and sensory experience of food or the
      continuous presence of a nasty taste, but can also result in loss of body weight
      and may have a negative influence on the quality of life. In this article both
      the physiology of chemosensory function and dysfunction of taste and smell are
      discussed as well as some clinical consequences and their treatment.

PMID- 11441716
TI  - [Burning mouth syndrome].
AB  - Symptoms of a burning sensation of the oral mucosa mainly occur in the elderly,
      more often in women than in men. Often accompanying symptoms are complaints of a
      dry mouth and taste disturbances, all together referred to as the burning mouth
      syndrome. In the majority of cases there is no detectable cause. Although a
      psychogenic aetiology has often been put forward, no scientific evidence has ever
      been provided on this matter. In the majority of patients the burning mouth
      syndrome will disappear spontaneously, although this may take many years.

PMID- 11441717
TI  - [Oral complications of anorexia nervosa, bulimia nervosa and other metabolic
      disorders].
AB  - Eating disorders like anorexia nervosa and boulimia nervosa may have consequences
      for both the oral tissues and the salivary glands. In the oral cavity these
      eating disorders result frequently in dental erosion, but also in dental caries.
      The salivary glands are regularly swollen without pain; a hypofunction in the
      salivary secretory process may develop resulting in dry mouth feelings. In this
      paper these aspects will be reviewed and illustrated with patient cases.

PMID- 11441718
TI  - [Considerations on vaccinations for the dental staff].
AB  - In this article the available vaccinations in the Netherlands that might be of
      value to dentistry are discussed. This in view of protection of both the patient
      and the medical worker. Furthermore vaccines that are necessary but do not exist
      or have not been developed yet, are mentioned. Of the available vaccinations, the
      one against hepatitis B is of the utmost importance. This has been stressed in
      the Netherlands from all sides for a long time already; nonetheless not all
      dental workers have been vaccinated up until now. The vaccines against human
      immunodeficiency virus (HIV) and viral hepatitis C rank high on the list of
      medical achievements most wanted.

PMID- 11441719
TI  - [Pain database of Oxford].

PMID- 11441720
TI  - Property, politics, and public health.

PMID- 11441721
TI  - An HIV agenda for the new administration.

PMID- 11441722
TI  - HIV in the late 1990s: what we don't know may hurt us.

PMID- 11441723
TI  - The Serostatus Approach to Fighting the HIV Epidemic: prevention strategies for
      infected individuals.
AB  - In the United States, HIV prevention programs have historically tailored
      activities for specific groups primarily on the basis of behavioral risk factors
      and demographic characteristics. Through the Serostatus Approach to Fighting the
      Epidemic (SAFE), the Centers for Disease Control and Prevention is now expanding
      prevention programs, especially for individuals with HIV, to reduce the risk of
      transmission as a supplement to current programs that primarily focus on reducing
      the risk of acquisition of the virus. For individuals with HIV, SAFE comprises
      action steps that focus on diagnosing all HIV-infected persons, linking them to
      appropriate high-quality care and prevention services, helping them adhere to
      treatment regimens, and supporting them in adopting and sustaining HIV risk
      reduction behavior. SAFE couple a traditional infectious disease control focus on
      the infected person with behavioral interventions that have been standard for HIV
      prevention programs.

PMID- 11441724
TI  - Journals of the plague years: documenting the history of the AIDS epidemic in the
      United States.
AB  - This commentary discusses several journalistic, literary, and historical accounts
      of the AIDS epidemic as it has unfolded in the United States over the past 2
      decades. By examining the different ways that different types of storytellers
      chronicle the political, social, public health, medical, and economic aspects of
      epidemic disease, this essay will demonstrate why the AIDS epidemic has been of
      such intense interest not only to physicians and public health experts but also
      to journalists, novelists, playwrights, memoirists, and historians. AIDS is a
      particularly fascinating example of society's broad concern with epidemics
      because it both is a global pandemic and, in recent years, has become a chronic
      disease.

PMID- 11441725
TI  - Expanding the research infrastructure for lesbian health.
AB  - Interest in research about lesbian health has increased dramatically since the
      late 1980s and gained national attention in 1999 when the Institute of Medicine
      published the groundbreaking report Lesbian Health: Current Assessment and
      Directions for the Future. In March 2000, the Department of Health and Human
      Services and partner organizations presented the Scientific Workshop on Lesbian
      Health, during which invited experts on lesbian health worked with federal
      representatives to develop action steps to implement recommendations in the
      Institute of Medicine report. National priorities were thus established for the
      emerging field of lesbian health research. Although researchers of various sexual
      orientation and gender identities will contribute to this field, lesbian
      researchers have a unique perspective and an important role to play. This
      commentary focuses on the preparedness of these individuals to respond to
      challenges set forth by the Institute of Medicine and Scientific Workshop
      reports. Despite differences in their academic backgrounds, lesbian researchers
      have reported common experiences and needs. Substantial proportions have
      encountered barriers because they were lesbians or conducted lesbian research,
      and many expressed willingness to mentor others, to help others to conduct
      research about lesbians, or both.

PMID- 11441726
TI  - Zoning, equity, and public health.
AB  - Zoning, the most prevalent land use planning tool in the United States, has
      substantial implications for equity and public health. Zoning determines where
      various categories of land use may go, thereby influencing the location of
      resulting environmental and health impacts. Industrially zoned areas permit
      noxious land uses and typically carry higher environmental burdens than other
      areas. Using New York City as a case study, the author shows that industrial
      zones have large residential populations within them or nearby. Noxious uses tend
      to be concentrated in poor and minority industrial neighborhoods because more
      affluent industrial areas and those with lower minority populations are rezoned
      for other uses, and industrial zones in poorer neighborhoods are expanded. Zoning
      policies, therefore, can have adverse impacts on public health and equity. The
      location of noxious uses and the pollution they generate have ramifications for
      global public health and equity; these uses have been concentrated in the world's
      poorer places as well as in poorer places within more affluent countries.
      Planners, policymakers, and public health professionals must collaborate on a
      worldwide basis to address these equity, health, and land use planning problems.

PMID- 11441727
TI  - Measles elimination: a mass immunization campaign in Romania.

PMID- 11441728
TI  - The color line: race matters in the elimination of health disparities.

PMID- 11441729
TI  - Them and us: the politics of population taxonomy.

PMID- 11441730
TI  - Paradigm lost: race, ethnicity, and the search for a new population taxonomy.
AB  - The Institute of Medicine (IOM) recently recommended that the National Institutes
      of Health (NIH) reevaluate its employment of "race," a concept lacking scientific
      or anthropological justification, in cancer surveillance and other population
      research. The IOM advised the NIH to use a different population classification,
      that of "ethnic group," instead of "race." A relatively new term, according to
      the IOM, "ethnic group" would turn research attention away from biological
      determinism and toward a focus on culture and behavior. This article examines the
      historically central role of racial categorization and its relationship to racism
      in the United States and questions whether dropping "race" from population
      taxonomies is either possible or, at least in the short run, preferable. In
      addition, a historical examination of "ethnicity" and "ethnic group" finds that
      these concepts, as used in the United States, derive in part from race and
      immigration and are not neutral terms; instead, they carry their own burden of
      political, social, and ideological meaning.

PMID- 11441731
TI  - Jogging and bone mineral density in men: results from NHANES III.
AB  - OBJECTIVES: This cross-sectional population-based study assessed the association
      of jogging with femoral bone mineral density (BMD) in men. METHODS: Data are from
      a nationally representative sample of 4254 men aged 20 to 59 years from the Third
      National Health and Nutrition Examination Survey (NHANES III). Total femoral BMD
      was measured by dual energy x-ray absorptiometry. Jogging was self-reported.
      RESULTS: Jogging (any vs none) was strongly associated with higher BMD in
      multivariate models (P < .01) for both young and middle-aged men. Men who jogged
      9 or more times per month had higher BMD levels than those who jogged only 1 to 8
      times per month (P = .01). CONCLUSIONS: Jogging is associated with higher femoral
      neck BMD in men. Additional large-scale studies that measure all aspects of
      jogging are warranted.

PMID- 11441732
TI  - HIV in the United States at the turn of the century: an epidemic in transition.
AB  - OBJECTIVES: The current status of and changes in the HIV epidemic in the United
      States are described. METHODS: Surveillance data were used to evaluate time
      trends in AIDS diagnoses and deaths. Estimates of HIV incidence were derived from
      studies done during the 1990s; time trends in recent HIV incidence were inferred
      from HIV diagnoses and seroprevalence rates among young persons. RESULTS: Numbers
      of deaths and AIDS diagnoses decreased dramatically during 1996 and 1997 but
      stabilized or declined only slightly during 1998 and 1999. Proportional decreases
      were smallest among African American women, women in the South, and persons
      infected through heterosexual contact, HIV incidence has been roughly constant
      since 1992 in most populations with time trend data, remains highest among men
      who have sex with men and injection drug users, and typically is higher among
      African Americans than other racial/ethnic groups. CONCLUSIONS: The epidemic
      increasingly affects women minorities, persons infected through heterosexual
      contact, and the poor. Renewed interest and investment in HIV and AIDS
      surveillance and surveillance of behaviors associated with HIV transmission are
      essential to direct resources for prevention to populations with greatest need
      and to evaluate intervention programs.

PMID- 11441733
TI  - Biomechanical and psychosocial risk factors for low back pain at work.
AB  - OBJECTIVES: This study determined whether the physical and psychosocial demands
      of work are associated with low back pain. METHODS: A case-control approach was
      used. Case subjects (n = 137) reported a new episode of low back pain to their
      employer, a large automobile manufacturing complex. Control subjects were
      randomly selected from the study base as cases accrued (n = 179) or were matched
      to cases by exact job (n = 65). Individual, clinical, and psychosocial variables
      were assessed by interview. Physical demands were assessed with direct workplace
      measurements of subjects at their usual jobs. The analysis used multiple logistic
      regression adjusted for individual characteristics. RESULTS: Self-reported risk
      factors included a physically demanding job, a poor workplace social environment,
      inconsistency between job and education level, better job satisfaction, and
      better coworker support. Low job control showed a borderline association.
      Physical-measure risk factors included peak lumbar shear force, peak load
      handled, and cumulative lumbar disc compression. Low body mass index and prior
      low back pain compensation claims were the only significant individual
      characteristics. CONCLUSIONS: This study identified specific physical and
      psychosocial demands of work as independent risk factors for low back pain.

PMID- 11441734
TI  - Causal influence of car mass and size on driver fatality risk.
AB  - OBJECTIVES: This study estimated how adding mass, in the form of a passenger, to
      a car crashing head-on into another car affects fatality risks to both drivers.
      The study distinguished the causal roles of mass and size. METHODS: Head-on
      crashes between 2 cars, one with a right-front passenger and the other with only
      a driver, were examined with Fatality Analysis Reporting System data. RESULTS:
      Adding a passenger to a car led to a 14.5% reduction in driver risk ratio (risk
      to one driver divided by risk to the other). To divide this effect between the
      individual drivers, the author developed equations that express each driver's
      risk as a function of causal contributions from the mass and size of both
      involved cars. Adding a passenger reduced a driver's frontal crash fatality risk
      by 7.5% but increased the risk to the other driver by 8.1%. CONCLUSIONS: The
      presence of a passenger reduces a driver's frontal crash fatality risk but
      increases the risk to the driver of the other car. The findings are applicable to
      some single-car crashes, in which the driver risk decrease is not offset by any
      increase in harm to others. When all cars carry the same additional cargo, total
      population risk is reduced.

PMID- 11441735
TI  - Underuse of invasive procedures among Medicaid patients with acute myocardial
      infarction.
AB  - OBJECTIVES: The purpose of this study was to determine whether underuse of
      cardiac procedures among Medicaid patients with acute myocardial infarction is
      explained by or is independent of fundamental differences in age, race, or sex
      distribution; income, coexistent illness; or location of care. METHODS:
      Administrative data from 226 hospitals in New York were examined for 11,579
      individuals hospitalized with a primary diagnosis of acute myocardial infarction.
      Use of various cardiac procedures was compared among Medicaid patients and
      patients with other forms of insurance. RESULTS: Medicaid patients were older,
      were more frequently African American and female, and had lower median household
      incomes. They also had a higher prevalence of hypertension, diabetes, lung
      disease, renal disease, and peripheral vascular disease. After adjustment for
      these and other factors, Medicaid patients were less likely to undergo cardiac
      catheterization, percutaneous transluminal coronary angioplasty, and any
      revascularization procedure. CONCLUSIONS: Factors other than age, race, sex,
      income, coexistent illness, and location of care account for lower use of
      invasive procedures among Medicaid patients. The influence of Medicaid insurance
      on medical practice and process of care deserves investigation.

PMID- 11441736
TI  - Effects of alcohol-related disease on hip fracture and mortality: a retrospective
      cohort study of hospitalized Medicare beneficiaries.
AB  - OBJECTIVES: This study investigated the effect of alcohol-related disease on hip
      fracture and mortality. METHODS: A retrospective cohort design was used. The
      study cohort consisted of hospitalized Medicare beneficiaries with alcohol
      related disease (n = 150,119) and randomly matched controls without alcohol
      related disease (n = 726,218) identified through the 1988-1989 inpatient claims
      file. Incidence rates of hip fracture and mortality were examined. RESULTS:
      During the study period, 20,620 patients developed hip fracture, with 6973 cases
      among patients with alcohol-related disease and 13,647 cases among patients
      without alcohol-related disease. After adjustment for potential confounders,
      patients with alcohol-related disease had a 2.6-fold increased risk of hip
      fracture relative to patients without alcohol-related disease (95% confidence
      interval = 2.5, 2.6). Patients with alcohol-related disease had a higher risk of
      mortality at 1 year after hip fracture. CONCLUSIONS: Alcohol-related disease
      increases the risk of hip fracture significantly and reduces long-term survival.
      The present results suggest that patients hospitalized for alcohol-related
      disease should be targeted for hip fracture prevention programs.

PMID- 11441737
TI  - Mental health services for youths in foster care and disabled youths.
AB  - OBJECTIVES: This study assessed whether mental health services for youths differ
      with respect to medical assistance aid category. METHODS: Computerized claims for
      15,507 youths with Medicaid insurance in a populous county of a mid-Atlantic
      state were used to establish population-based prevalence estimates of mental
      disorders and psychotherapeutic treatments during 1996. RESULTS: An analysis of
      service claims revealed that the prevalence of mental disorders among youths
      enrolled in foster care (57%) was twice that of youths receiving Supplemental
      Security Income (SSI; 26%) and nearly 15 times that of other youths receiving
      other types of aid (4%). Rates of mental health service use were pronounced among
      foster care youths aged 6 to 14 years. Attention deficit/hyperactivity disorder,
      depression, and developmental disorders were the most prevalent disorders.
      Stimulants, antidepressants, and anticonvulsants were the most prevalent
      medications. CONCLUSIONS: Youths enrolled in foster care and youths receiving SSI
      use far more mental health services than do youths in other aid categories.
      Additional research should evaluate the complexity and outcomes of mental health
      services for youths in foster care.

PMID- 11441738
TI  - Counteracting tobacco motor sports sponsorship as a promotional tool: is the
      tobacco settlement enough?
AB  - OBJECTIVES: This study sought to quantify television advertising exposure
      achieved by tobacco companies through sponsorship of motor sports events and to
      evaluate the likely effect of the Master Settlement Agreement on this
      advertising. METHODS: Data from Sponsors Report, which quantifies the exposure
      that sponsors of selected televised sporting events receive during broadcasts of
      those events, were compiled for all motor sports events covered by the service
      for the period 1997 through 1999. RESULTS: From 1997 through 1999, tobacco
      companies achieved 169 hours of television advertising exposure and $410.5
      million of advertising value for their products by sponsoring motor sports
      events. If tobacco companies comply with the Master Settlement Agreement and
      maintain their advertising at 1999 levels, they will still be able to achieve
      more than 25 hours of television exposure and an equivalent television
      advertising value of $99.1 million per year. CONCLUSIONS: Despite a federal ban
      on tobacco advertising on television, tobacco companies achieve the equivalent of
      more than $150 million in television advertising per year through their
      sponsorship of motor sports events. The Master Settlement Agreement likely will
      do little to address this problem.

PMID- 11441739
TI  - Remission from drug abuse over a 25-year period: patterns of remission and
      treatment use.
AB  - OBJECTIVES: Using an epidemiologically obtained sample, we examined patterns of
      illicit drug use, abuse, and remission over a 25-year period and recent treatment
      use. METHODS: The surviving members of the cohort (n = 841), previously surveyed
      in 1972 and 1974, comprised 3 subsamples of Vietnam War enlisted men and civilian
      controls. Retrospectively obtained year-to-year measures from the 1996-1997
      survey included use and remission of sedatives, stimulants, marijuana, cocaine,
      and opiates, as well as substance abuse and psychiatric treatment use. RESULTS:
      Relatively stable patterns of frequent use in adulthood were found, with the mean
      duration from initiation to the last remission ranging from 9 to 14 years. A
      majority attempted to quit; however, most did not use traditional drug treatment
      in their last attempts. Fewer than 9% of the then-current drug users were treated
      in inpatient or outpatient settings at the time of data collection. CONCLUSIONS:
      Most drug abusers who had started using drugs by their early 20s appeared to
      gradually achieve remission. Spontaneous remission was the rule rather than the
      exception. Nonetheless, considerable unmet needs existed for those who had
      continued use into middle age.

PMID- 11441740
TI  - On the wrong side of the tracts? Evaluating the accuracy of geocoding in public
      health research.
AB  - OBJECTIVES: This study sought to determine the accuracy of geocoding for public
      health databases. METHODS: A test file of 70 addresses, 50 of which involved
      errors, was generated, and the file was geocoded to the census tract and block
      group levels by 4 commercial geocoding firms. Also, the "real world" accuracy of
      the best-performing firm was evaluated. RESULTS: Accuracy rates in regard to
      geocoding of the test file ranged from 44% (95% confidence interval [CI] = 32%,
      56%) to 84% (95% CI = 73%, 92%). The geocoding firm identified as having the best
      accuracy rate correctly geocoded 96% of the addresses obtained from the public
      health databases. CONCLUSIONS: Public health studies involving geocoded databases
      should evaluate and report on methods used to verify accuracy.

PMID- 11441741
TI  - Circumstances at HIV diagnosis and progression of disease in older HIV-infected
      Americans.
AB  - OBJECTIVES: This study identified age-related differences in diagnosis and
      progression of HIV by analyzing a nationally representative sample of HIV
      infected adults under care in the United States. METHODS: We compared older (> or
      = 50 years) and younger participants stratified by race/ethnicity. Regression
      models controlled for demographic, therapeutic, and clinical factors. RESULTS:
      Older non-Whites more often had HIV diagnosed when they were ill. Older and
      younger patients were clinically similar. At baseline, however, older non-Whites
      had fewer symptoms and were less likely to have AIDS, whereas at follow-up they
      had a trend toward lower survival. CONCLUSIONS: Later HIV diagnosis in non-Whites
      merits public health attention; clinical progression in this group requires
      further study.

PMID- 11441742
TI  - Epidemiologic trends in the hospitalization of elderly Medicare patients for
      pneumonia, 1991-1998.
AB  - OBJECTIVES: This study determined hospitalization rates of elderly Americans for
      pneumonia from 1991 through 1998. METHODS: Epidemiologic data were described for
      273,143 pneumonia hospitalizations. RESULTS: Annual hospitalizations for
      aspiration pneumonia increased by 93.5%. Pneumonia hospitalization rates
      increased steeply with age, especially among men. Black men were at highest risk
      for aspiration, unspecified, Klebsiella, "other gram-negative," and
      staphylococcal pneumonia; White men had the highest Haemophilus and pneumococcal
      pneumonia rates. Among women, Blacks predominated in aspiration and Klebsiella
      pneumonia; Whites had the highest Haemophilus and bronchopneumonia rates.
      CONCLUSIONS: An epidemic of hospitalization for aspiration pneumonia smoldered
      over 8 years. Significant disparities existed in hospitalization risks by race,
      sex, and principal diagnosis.

PMID- 11441743
TI  - Measuring statewide merchant compliance with tobacco minimum age laws: the
      Massachusetts experience.
AB  - OBJECTIVES: This study evaluated merchant compliance with laws prohibiting the
      sale of tobacco to minors in Massachusetts. METHODS: Stratified cluster sampling
      was used to select outlets from which youths aged 13 to 17 years attempted to
      purchase tobacco. RESULTS: Illegal sales were more common when the youth
      purchasing the tobacco was older, when the clerk was male, and when tobacco was
      obtained from a self-service display or unlocked vending machine. Failure to
      request proof of age was the strongest predictor of illegal sales. CONCLUSIONS:
      Measured compliance rates are strongly influenced by the age of the youths used
      to purchase tobacco.

PMID- 11441744
TI  - Immunization and symptoms of atopic disease in children: results from the
      International Study of Asthma and Allergies in Childhood.
AB  - OBJECTIVES: This study tested the hypothesis that immunization is related to the
      prevalence of atopic disease in childhood. METHODS: We used data from the
      International Study of Asthma and Allergies in Childhood to perform an ecologic
      analysis of national and local immunization rates for tuberculosis, diphtheria
      and tetanus toxoids and pertussis (DTP), and measles and prevalence of atopic
      disease symptoms (asthma, allergic rhinoconjunctivitis, and atopic eczema).
      RESULTS: In 13- to 14-year-old children, there were significant negative
      associations with local birth-year immunization rates for DTP and measles but
      none with rates for tuberculosis. No associations were found in 6- to 7-year-old
      children. No associations with national immunization rates were found.
      CONCLUSIONS: International variations in childhood atopic diseases are unlikely
      to be explained by variations in immunization.

PMID- 11441745
TI  - Tobacco, betel quid, alcohol, and illicit drug use among 13- to 35-year-olds in I
      Lan, rural Taiwan: prevalence and risk factors.
AB  - OBJECTIVES: This study determined the prevalence of and risk factors for
      substance use among rural Taiwanese. METHODS: We used a survey of a
      representative sample of 6318 participants aged 13 to 35 years in I-Lan, Taiwan,
      in 1996 through 1997. RESULTS: Perceived use of illicit drugs by peers, tobacco
      smoking, betel quid chewing, and male gender were the strongest predictors of
      illicit drug use. The prevalence of illicit drug use ranged from 0.3% among those
      who did not use any other substance to 7.1% among those using tobacco, betel
      quid, and alcohol. CONCLUSIONS: Preventive measures should address substance use
      in general rather than aiming at single substances.

PMID- 11441746
TI  - Activity limitations reported in the National Health Interview Survey: an anomaly
      and its effect on estimates of national well-being.

PMID- 11441747
TI  - California adolescents offer a glimpse into the future of multi-ethnicity.

PMID- 11441748
TI  - Emergency contraceptive pills can prevent abortion.

PMID- 11441749
TI  - Adults buy cigarettes for underaged youths.

PMID- 11441750
TI  - Population growth.

PMID- 11441751
TI  - Do census data reflect true female mortality?

PMID- 11441752
TI  - 2000 presidential address: eliminating health disparities.

PMID- 11441753
TI  - Humane resources. In defense of hugs in an age of paranoia.

PMID- 11441754
TI  - Scope of practice.

PMID- 11441755
TI  - HIV-positive youths.

PMID- 11441756
TI  - A preceptor incentive program.

PMID- 11441757
TI  - Preventing food- and water-borne illnesses.

PMID- 11441758
TI  - Hydrofluoric acid burns.

PMID- 11441759
TI  - HIV drug resistance and nursing practice.

PMID- 11441760
TI  - Adherence to HIV regimens: 10 vital lessons.

PMID- 11441761
TI  - HIV prevention: what works?

PMID- 11441762
TI  - HIV and AIDS: separating fact from fiction.

PMID- 11441763
TI  - Young women wanted.

PMID- 11441764
TI  - Privacy: the patient's right.

PMID- 11441765
TI  - HIV: still a problem of sex. Still a problem of bigotry.

PMID- 11441766
TI  - Staving off AIDS in Malawi.

PMID- 11441767
TI  - Working with glutaraldehyde.

PMID- 11441768
TI  - Clinical guidelines for the treatment of depressive disorders, I. Definitions,
      prevalence, and health burden.
AB  - BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for
      Mood and Anxiety Treatments partnered to produce clinical guidelines for
      psychiatrists for the treatment of depressive disorders. METHODS: A standard
      guidelines development process was followed. Relevant literature was identified
      using a computerized Medline search supplemented by review of bibliographies.
      Operational criteria were used to rate the quality of scientific evidence, and
      the line of treatment recommendations included consensus clinical opinion. This
      section on "Definitions, Prevalence, and Health Burden" was 1 of 7 articles
      drafted and reviewed by clinicians. Revised drafts underwent national and
      international expert peer review. RESULTS: The 1-year prevalence rate of major
      depressive disorder (MDD) in Canada is 3.2% to 4.6%, similar to the rates in
      other countries. MDD frequently runs a chronic or recurrent course and carries
      high risks for mortality and morbidity. The significant economic costs and
      disability associated with depressive illness are reduced by effective treatment.
      CONCLUSIONS: MDD is a prevalent medical condition that results in a significant
      health burden in the world. Vigorous efforts to improve diagnosis, treatment, and
      prevention are indicated to reduce the societal and personal costs of depressive
      disorders.

PMID- 11441769
TI  - Clinical guidelines for the treatment of depressive disorders. II. Principles of
      management.
AB  - BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for
      Mood and Anxiety Treatments partnered to produce clinical guidelines for
      psychiatrists for the treatment of depressive disorders. METHODS: A standard
      guidelines development process was followed. Relevant literature was identified
      using a computerized Medline search supplemented by review of bibliographies.
      Operational criteria were used to rate the quality of scientific evidence, and
      the line of treatment recommendations included consensus clinical opinion. This
      section on "Principles of Management" is 1 of 7 articles drafted and reviewed by
      clinicians. Revised drafts underwent national and international expert peer
      review. RESULTS: The principles and goals of psychiatric management with
      psychotherapy and pharmacotherapy are reviewed. Two phases of treatment, acute
      and maintenance, are identified. Special topics, including inpatient management,
      suicide management, and medical-legal issues are also discussed. CONCLUSIONS:
      These principles of psychiatric management provide a framework for the use of
      specific treatments for depressive disorders.

PMID- 11441770
TI  - Clinical guidelines for the treatment of depressive disorders. III.
      Psychotherapy.
AB  - BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for
      Mood and Anxiety Treatments partnered to produce clinical guidelines for
      psychiatrists for the treatment of depressive disorders. METHODS: A standard
      guidelines development process was followed. Relevant literature was identified
      using a computerized Medline search supplemented by review of bibliographies.
      Operational criteria were used to rate the quality of scientific evidence, and
      the line of treatment recommendations included consensus clinical opinion. This
      section on "Psychotherapy" is 1 of 7 articles drafted and reviewed by clinicians.
      Revised drafts underwent national and international expert peer review. RESULTS:
      Recommendations are given for the use of psychotherapy in the treatment of
      depressive disorders. Considerable evidence shows that specific, short-term
      psychotherapies including cognitive-behavioural therapy (CBT) and interpersonal
      therapy (IPT) are effective acute-phase treatments. There is also evidence that
      group and marital/couples formats of psychotherapy are effective. There is only
      limited evidence that psychotherapy is effective for maintenance treatment of
      depressive disorders. CONCLUSIONS: Psychotherapy is effective in the treatment of
      depressive disorders. Despite the evidence for effectiveness of specific
      psychotherapies, there is still limited access to these treatments in the
      community.

PMID- 11441771
TI  - Clinical guidelines for the treatment of depressive disorders. IV. Medications
      and other biological treatments.
AB  - BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for
      Mood and Anxiety Treatments partnered to produce clinical guidelines for
      psychiatrists for the treatment of depressive disorders. METHODS: A standard
      guidelines development process was followed. Relevant literature was identified
      using a computerized Medline search supplemented by review of bibliographies.
      Operational criteria were used to rate the quality of scientific evidence, and
      the line of treatment recommendations included consensus clinical opinion. This
      section, "Medications and Other Biological Treatments," is 1 of 7 articles that
      were drafted and reviewed by clinicians. Revised drafts underwent national and
      international expert peer review. RESULTS: Evidence-based recommendations are
      presented for 1) choosing an antidepressant, based on efficacy, tolerability, and
      safety; 2) the optimal use of antidepressants, including augmentation,
      combination, and switching strategies; 3) maintenance treatment; and 4)
      electroconvulsive therapy (ECT), light therapy, and additional somatic
      treatments. Evidence from metaanalyses is presented first, followed by
      conclusions from randomized controlled trials (RCTs) and, if appropriate, open
      label data. CONCLUSIONS: There is significant evidence to support the role of
      selective serotonin reuptake inhibitors (SSRIs), novel agents, and classic agents
      in the treatment of major depressive disorder (MDD). There is also evidence to
      support the use of somatic treatments, including ECT and light therapy, for some
      patients with MDD. There is limited evidence for the use of specific medications
      to treat subtypes of MDD. There is emerging evidence to support augmentation and
      combination strategies for patients previously nonresponsive to medication.

PMID- 11441772
TI  - Clinical guidelines for the treatment of depressive disorders. V. Combining
      psychotherapy and pharmacotherapy.
AB  - BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for
      Mood and Anxiety Treatments partnered to produce clinical guidelines for
      psychiatrists for the treatment of depressive disorders. METHODS: A standard
      guidelines development process was followed. Relevant literature was identified
      using a computerized Medline search supplemented by review of bibliographies.
      Operational criteria were used to rate the quality of scientific evidence, and
      the line of treatment recommendations included consensus clinical opinion. This
      section, "Combining Psychotherapy and Pharmacotherapy," was 1 of 7 articles
      drafted and reviewed by clinicians. Revised drafts underwent national and
      international expert peer review. RESULTS: Recommendations are given for the use
      of combined psychotherapy and pharmacotherapy for the treatment of depressive
      disorders. Three methods of combined treatment are identified: concurrent
      treatment (psychotherapy plus pharmacotherapy) for the acute-treatment phase,
      sequential treatment (adding the other treatment for nonresponders or partial
      responders to monotherapy in the acute-treatment phase), and crossover treatment
      (switching to psychotherapy for the maintenance-treatment phase after response to
      pharmacotherapy in the acute phase). CONCLUSIONS: Combined treatment with
      psychotherapy and pharmacotherapy is widely used in clinical practice. The
      recommendations for use of combined treatment are, however, based on only a
      limited evidence base.

PMID- 11441773
TI  - Clinical guidelines for the treatment of depressive disorders. VI. Special
      populations.
AB  - BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for
      Mood and Anxiety Treatments partnered to produce clinical guidelines for
      psychiatrists for the treatment of depressive disorders. METHODS: A standard
      guidelines development process was followed. Relevant literature was identified
      using a computerized Medline search supplemented by review of bibliographies.
      Operational criteria were used to rate the quality of scientific evidence, and
      the line of treatment recommendations included consensus clinical opinion. This
      section, "Special Populations," is 1 of 7 articles that were drafted and reviewed
      by clinicians. Revised drafts underwent national and international expert peer
      review. RESULTS: This section reports on the prevalence, course, and outcome of
      depression for specific populations. Psychological, pharmacologic, and other
      biological treatment options for these populations--children and adolescents, the
      elderly, women at times of increased risk within the reproductive cycle, and
      specific ethnocultural groups--are critically evaluated. CONCLUSIONS: Major
      depressive disorder (MDD) is prevalent across the lifespan. In general, clinical
      presentations are more similar than different across age, sex, and cultural
      divides. Although less evidence is available for the efficacy of treatments in
      these subpopulations than in mid-life patients, comparable rates of response for
      pharmacotherapies, electroconvulsive therapy (ECT), and, in some cases, evidence
      based psychotherapies have been reported.

PMID- 11441774
TI  - Clinical guidelines for the treatment of depressive disorders. VII. Comorbidity.
AB  - BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for
      Mood and Anxiety Treatments partnered to produce clinical guidelines for
      psychiatrists for the treatment of depressive disorders. METHODS: A standard
      guidelines development process was followed. Relevant literature was identified
      using a computerized Medline search supplemented by review of bibliographies.
      Operational criteria were used to rate the quality of scientific evidence, and
      the line of treatment recommendations included consensus clinical opinion. This
      section, on Axis I, Axis II, and Axis III comorbidity, is 1 of 7 articles that
      were drafted and reviewed by clinicians. Revised drafts underwent national and
      international expert peer review. RESULTS: Comorbid depression on Axis I is
      particularly prevalent in patients with anxiety disorders, substance use
      disorders, and eating disorders, but it also occurs in patients with
      schizophrenia, attention-deficit hyperactivity disorder (ADHD), and dementia.
      Depressive comorbidity has implications for assessment, management, and outcome.
      The relation between depression and personality disorders is complex. Patient
      with this comorbidity often require longer, more intense, and multimodal
      therapies. Depression is also prevalent in medical illnesses, requires careful
      diagnosis, and responds to standard antidepressant treatments. CONCLUSIONS:
      Comorbidity can influence the course and outcome of both associated conditions.
      Depression-specific psychotherapy and/or pharmacotherapy should be considered
      when comorbid depression is diagnosed.

PMID- 11441775
TI  - Evidence-based psychiatry: the pros and cons.

PMID- 11441776
TI  - ["What's up, doc?" The context, limitations, and issues for clinicians in
      evidence-based medicine].
AB  - BACKGROUND: The evidence-based medicine approach could be considered a new name
      given to the contemporary medicine dialectics between the practice of an art and
      the insight provided by the best scientific data. METHODS: In this 3-part
      article, the background is introduced, then the design limits of the approach are
      shown through an example of metaanalysis applied to 4 psychiatric situations, and
      the conclusion is left to a clinician. RESULTS: In the background, evidence-based
      medicine is first associated with the period of budget cuts, then with the
      widespread popularity of the Internet. A few snags in this seemingly flawless
      system are seen when the subjective items involved in metaanalysis are taken into
      account. There are also problems linked to unpublished data, homogenization of
      populations studied, and the assumption that only random studies lead to valid
      scientific knowledge. The clinician will probably not be surprised and will link
      this to the old debate between empiricists and rationalists. CONCLUSION: In its
      purest form, evidence-based medicine supports the necessary continuous inquiry
      about our practices.

PMID- 11441777
TI  - Recent advances in evidence-based psychiatry.
AB  - BACKGROUND: There is increasing interest in the potential contribution of
      evidence-based medicine to clinical decision making in psychiatry. In this
      article, we describe some of the recent advances in evidence-based psychiatry and
      outline future challenges. METHOD: Narrative review. CONTENT: The successful
      introduction of evidence-based practice into psychiatry requires the acquisition
      of new skills by clinicians. It is also important that policy statements that aim
      to be evidence-based, such as clinical practice guidelines, use rigorous methods
      to synthesize the primary evidence and do not overlook its limitations. One
      result of the systematic reviewing of evidence is the identification of important
      residual clinical uncertainties. Primary research can then be focused on these
      questions. For questions regarding therapy in psychiatry, it will be necessary to
      undertake some large, simple randomized trials. Making the best available
      evidence readily accessible in a clinical setting, however, remains a significant
      challenge. CONCLUSIONS: Collaboration between clinicians, researchers, policy
      makers, and those involved in information technology is required to optimize the
      contribution of evidence-based medicine in psychiatry.

PMID- 11441778
TI  - Canadian and American psychiatrists' attitudes toward dissociative disorders
      diagnoses.
AB  - OBJECTIVE: To compare the opinions of Canadian psychiatrists regarding
      dissociative disorder diagnoses with those of previously surveyed American
      psychiatrists. METHOD: We sent a 1-page questionnaire to a stratified
      representative sample of 550 Canadian psychiatrists. RESULTS: Eighty percent of
      Canadian psychiatrists responded. Fewer than one-third replied that dissociative
      amnesia and dissociative identity disorder should be included without
      reservations in the DSM-IV; fewer than 1 in 7 felt that the validity of these
      diagnoses was supported by strong scientific evidence. French- and English
      speaking Canadians had similar opinions. Overall, Canadians were significantly
      less accepting than Americans. CONCLUSION: Both Canadian and American
      psychiatrists show little consensus regarding the diagnostic status or scientific
      validity of dissociative amnesia and dissociative identity disorder.

PMID- 11441779
TI  - Epidemiology of problem gambling in Prince Edward Island: a Canadian microcosm?
AB  - OBJECTIVES: To gather information that describes the extent of gambling and
      problem gambling in Prince Edward Island (PEI), to rigorously analyze the
      relation between gambling activities and problem gambling, to document cognitive
      and emotional correlates of problem gambling, and to identify an at-risk gambling
      group. METHOD: We selected a random, stratified sample (n = 809) to represent the
      adult population of PEI. We administered both the South Oaks Gambling Screen
      (SOGS) and an early version of the Canadian Problem Gambling Index (CPGI) to
      participants who had gambled. RESULTS: The current rate of problem gambling was
      3.1%. Problem gamblers were likely to be under age 30 years, to be single, and to
      report cognitive, emotional, and substance abuse correlates. Multiple-regression
      analysis identified a unique and substantial relation between problem gambling
      and video lottery terminal (VLT) use. We identified a group of at-risk gamblers
      (scoring 1 or 2 on the SOGS), comprising 14% of the sample. CONCLUSIONS: Gambling
      and problem gambling patterns in PEI resemble those in most other provinces. The
      relation found between problem gambling, VLT use, and cognitive, emotional, and
      substance use correlates should apply to the greater population as well.

PMID- 11441780
TI  - A profile of Canadian adults seeking treatment for gambling problems and
      comparisons with adults entering an alcohol treatment program.
AB  - OBJECTIVE: To empirically describe problem gambling in the Canadian context,
      using a large sample of treatment-seeking adults. METHOD: We assessed 1376
      Winnipeg adults seen in the problem gambling program at the Addictions Foundation
      of Manitoba (AFM) and compared them with 11,661 alcohol-program clients seen over
      the same 4-year time period. RESULTS: Sociodemographic comparisons revealed a
      higher-functioning profile for individuals with gambling problems compared with
      those having alcohol problems (for example, higher education and income levels).
      Most gambling clients did not report symptoms of substance abuse, but almost 70%
      smoked cigarettes. The most frequent gambling activity involved the use of video
      lottery terminals (VLTs) in local bars and restaurant lounges. Lottery tickets,
      bingo, and even casinos were infrequently used by problem gamblers. CONCLUSIONS:
      In several ways, gambling problems in the Canadian context represent a relatively
      novel form of addiction that many clinicians have not previously encountered.
      VLTs were only recently introduced in many parts of Canada, and they appear to
      play a large role in the expression of problem gambling. One potential reason for
      the popularity of neighbourhood bars over casinos or US venues is the increased
      availability of legalized gambling in the community.

PMID- 11441781
TI  - A prospective study of sex-specific effects of major depression on alcohol
      consumption.
AB  - OBJECTIVE: To evaluate the impact of major depression on alcohol use in the
      Canadian general population. METHOD: This study was based on a 2-year follow-up
      of the Canadian National Population Health Survey (NPHS) longitudinal cohort.
      Subjects reporting various patterns of drinking, with and without major
      depression, were selected using the 1994-95 NPHS data. Data collected during a
      reevaluation of these subjects 2 years later were analyzed to determine whether
      having major depression at the 1994-95 interview predicted subsequent changes in
      drinking patterns. RESULTS: Subjects who were depressed in 1994-95 were generally
      not at higher risk of starting drinking or drinking more frequently than once a
      week. However, women who were depressed, especially those who were 19 years old
      or older, were at higher risk of having 5 or more drinks at least once monthly.
      CONCLUSION: These results confirm that mood disorders can impact on alcohol
      consumption in women. A component of the well-known association between alcohol
      consumption and major depression is due to "reverse" causal effects. Proper
      management of depression in women may contribute to the prevention of problem
      drinking.

PMID- 11441782
TI  - Assessing fitness to stand trial: the utility of the Fitness Interview Test
      (revised edition).
AB  - OBJECTIVE: In Canada most evaluations of fitness to stand trial are conducted on
      an inpatient basis. This costs time and money, and deprives those defendants
      remanded for evaluation of liberty. This research assessed the predictive
      efficiency of the Fitness Interview Test, revised edition (FIT) as a screening
      instrument for fitness to stand trial. METHOD: We compared decisions about
      fitness to stand trial, based on the FIT, with the results of institution-based
      evaluations for 2 samples of men remanded for inpatient fitness assessments.
      RESULTS: The FIT demonstrates excellent utility as a screening instrument. The
      FIT shows good sensitivity and negative predictive power, which suggests that it
      can reliably screen those individuals who are clearly fit to stand trial, before
      they are remanded to an inpatient facility for a fitness assessment. CONCLUSION:
      We discuss the implications for evaluating fitness to stand trial, particularly
      in terms of the need for community-based alternatives to traditional forensic
      assessments.

PMID- 11441783
TI  - Crowding and violence on psychiatric wards: explanatory models.
AB  - OBJECTIVE: Violence is widely prevalent on acute-care psychiatric wards, and
      crowding has been identified as a major risk factor. This paper explores why
      patients may respond to crowding with violence. METHOD: We carried out a
      literature review on Medline, using the key words "violence" and "crowding." We
      conducted an additional hand search of the references collected from the reviewed
      papers. RESULTS: Factors specific to the relation between crowding on acute-care
      inpatient psychiatric wards and violence can be divided under the following
      headings: 1) patient density, privacy, and control; 2) ward architecture; 3) the
      social organization of psychiatric wards; 4) interpersonal space; 5) phylogenic
      theories; and 6) anthropological theories of human behaviour. CONCLUSIONS: We
      offer explanatory models for this relation and suggest strategies to counter the
      effects of crowding. Recommendations are made for future studies.

PMID- 11441784
TI  - "Diet pills" and major depression in the Canadian population.
AB  - OBJECTIVE: To evaluate epidemiological associations between self-reported diet
      pill consumption and major depressive episodes (MDEs), using data from a large
      scale, cross-sectional survey of the Canadian population. METHODS: Data from the
      National Population Health Survey (NPHS) were used in this analysis. The NPHS
      interview included a brief version of the Composite International Diagnostic
      Interview (CIDI) depression section, known as the CIDI Short Form for Major
      Depression (CIDI-SFMD), as well as provision for self-reported medication use.
      RESULTS: Approximately 0.5% of the population reported the use of diet pills.
      Diet pill use was more common among women than among men. At the time of data
      collection (1996-1997), the most commonly used medication was fenfluramine (since
      withdrawn from the market because of cardiovascular toxicity). The use of these
      medications was strongly associated with MDE: the annual prevalence among persons
      reporting use was 17.1% (95% CI, 8.6 to 25.6), approximately 4 times the
      underlying population rate. CONCLUSIONS: Because the NPHS was a general health
      survey, and because self-reported exposure to these medications was relatively
      uncommon, the data did not permit a detailed multivariate analysis. These
      findings, however, indicate that depressive psychopathology is strongly
      associated with the use of appetite-suppressant medications.

PMID- 11441785
TI  - The misidentification of Clerambault's and Kandinsky-Clerambault's syndromes.
AB  - Eponymic terms or eponyms are labels describing phenomena that reflect the
      name(s) of the person(s) who first described the phenomena. Using a similar term
      to describe different forms of pathology leads to a muddle. In this paper, we
      describe "Clerambault's syndrome" and "Kandinsky-Clerambault's syndrome" and
      discuss and clarify the confusion surrounding these different syndromes.

PMID- 11441786
TI  - Neurobiology of the use of selective serotonin reuptake inhibitors during
      pregnancy: response.

PMID- 11441787
TI  - Tryptophan for treatment of rapid-cycling bipolar disorder comorbid with
      fibromyalgia.

PMID- 11441788
TI  - Laryngeal dystonia in psychiatry.

PMID- 11441789
TI  - Risperidone-induced edema.

PMID- 11441790
TI  - Mania associated with an energy drink: the possible role of caffeine, taurine,
      and inositol.

PMID- 11441791
TI  - Using databases to prevent inpatient morbidity.

PMID- 11441792
TI  - Gabapentin as prophylaxis against steroid-induced mania.

PMID- 11441793
TI  - St John's wort-induced sexual dysfunction.

PMID- 11441794
TI  - Olanzapine-related hyperglycemia in a nondiabetic woman.

PMID- 11441795
TI  - Suspected neuroleptic catatonia induced by clozapine.

PMID- 11441796
TI  - International effort on geriatric oral health.

PMID- 11441797
TI  - A comparative study of propolis and saline application on human dentin. A SEM
      study.
AB  - The purpose of this study was to compare the texture changes of dentinal surfaces
      after the application of propolis and saline. Twenty-four recently extracted
      human premolar teeth were obtained from the Division of Oral and Maxillofacial
      Surgery, King Saud University, College of Dentistry, Riyadh. The teeth were
      classified as sound, periodontally involved and with recession. Forty-eight, 3 x
      3 mm dentin disc specimens were prepared and only 24 specimens were treated with
      propolis (pH 8.5) and saline (pH 6). They were treated in 4 categories i.e.: (1)
      no application of any material (control); (2) propolis for 60 seconds; (3)
      propolis for 120 seconds and (4) saline for 60 seconds. All experimental
      specimens were burnished with cotton pellet with propolis and saline for the
      prescribed time. All specimens were prepared for scanning electron microscopy
      (SEM) with sputter technique, (Blomlof and Lindskog, 1995), and examined in the
      SEM (Jeol, Japan) operated at 25 KV with a tilt angle between 0-30 degrees. The
      bar was 10 mm and magnification 2000x. There were dentinal tubules occlusion in
      all three groups of dentin treated with propolis for 120 seconds. The propolis
      was better than saline in occluding dentinal tubules. It may be suggested that
      further research is needed for double blind clinical trials of propolis in
      patients with dentinal hypersensitivity.

PMID- 11441798
TI  - Immunofluorescence in oral lichen planus and oral lichenoid reaction. A review.
AB  - Oral lichen is a mucocutaneous disorder, which presents a confusing array of
      patterns and forms. Despite the reported differences between the classical lichen
      planus and lichenoid reaction, several reports have concurred with this lack of
      distinguishing features. As of yet there is no specific test for lichenoid
      reaction, although resolution and recurrence of lichenoid reaction on withdrawal
      and exposure to the drug is probably diagnostic. Thus when the clinical and
      histopathologic evaluation cannot confirm the diagnosis satisfactorily, the use
      of immunofluorescent examination is of great importance. Early diagnoses of these
      conditions are more likely with adjunctive use of immunofluorescent examination.
      Further, this tool may provide an insight into the pathogenesis of these
      disorders.

PMID- 11441800
TI  - Evaluation of immunoglobulin G synthesizing plasma cells in periapical granuloma
      and cyst.
AB  - Immunoglobulin synthesizing plasma cells for IgG were quantitated in 20
      periapical granulomas and 20 periapical cysts, using unlabelled antibody
      peroxidase-antiperoxidase complex method. Result showed that immunoglobulin G
      producing plasma cells were predominant in periapical cyst as compared with
      periapical granuloma. A statistical significant relation was observed between
      these two lesions.

PMID- 11441801
TI  - Calcifying odontogenic cyst. Report of two cases.
AB  - Calcifying odontogenic cyst(COC) is an uncommon developmental odontogenic cyst
      and was first described by Gorlin in 1962. It is considered as extremely rare and
      accounts for only 1% of the jaw cysts reported. Here, we present two cases of
      which one occurred in a 32 year old female with a swelling in the lower anterior
      region crossing the midline and another in a 29 year old male with a swelling in
      the upper anterior region without crossing the midline. The radiograph revealed a
      well circumscribed radiolucency in the first case and with some specks of
      opacities in the second case. It was not associated with any missing or impacted
      tooth. Histopathological examination was done with Hematoxylin and Eosin and in
      addition it was studied immunohistochemically for cytokeratin. The Classical
      histological features of lining epithelium in the form of cords, presence of
      ghost cells and some amount of dentinoid tissue were seen. The nature of COC is
      controversial. Here we have discussed the controversies regarding COC as well as
      the various proposed classifications for this lesion. Based on the
      histopathological findings, the diagnosis was confirmed as calcifying odontogenic
      cyst. These cases are presented here for its rarity.

PMID- 11441802
TI  - Myoepithelioma. A case report.
AB  - A rare case of oral myoepithelioma is reported. The tumour was composed of
      plasmacytoid type of myoepithelial cells. These plasmacytoid cells or hyaline
      cells exhibited a diffuse positivity for pancytokeratin, S-100 and vimentin in
      their cytoplasm. Studies have to be performed in order to find out whether the
      myoepithelial cells M.E. of plasmacytoid type are true M.E. cells of not.

PMID- 11441803
TI  - Study of drug utilization pattern in dental OPD at tertiary care teaching
      hospital.
AB  - Irrational prescribing is a global phenomenon. The objective of the study was to
      find out the prescribing practices of dental prescribers in a tertiary care
      teaching hospital with special emphasis on the utilization of antimicrobial
      agents. A prospective study was conducted in the month of March 2000. A total of
      491 prescriptions were collected randomly. Prescribing pattern was analyzed using
      WHO basic drug indicators. The average number of drugs for prescription was 2.4.
      78.8% of all prescriptions contained antimicrobial agents. It was most commonly
      prescribed (40.37%) group of drugs followed by anti-inflammatory and analgesics
      (33.8%). Fixed dose combination of ampicillin and cloxacillin was most commonly
      prescribed antimicrobial agents. Prophylactic use of AMA (78%) was more than
      therapeutic purpose (21.9%). Prophylactic use of antimicrobial agents was
      irrational in all the cases as duration for the use of antimicrobial agents was
      5.1 +/- 0.5 days. Fixed dose combinations (45%), drugs by brand name (98.5%) were
      frequently used. Drug prescribed from Essential Drug List was maximum when one
      drug was prescribed. Results indicate that there is a scope for improving
      prescribing habits and minimizing the use of antimicrobial agents. This could be
      facilitated by periodic education to the prescribers.

PMID- 11441804
TI  - Visceral organ involvement is infrequent in oral submucous fibrosis (OSF).
AB  - Associated visceral organ involvement evidence by systemic fibrosis has not been
      explored in oral submucous fibrosis (OSF). The investigations in this aspect were
      limited to loco-regional sites of naso/oropharynx and oesophagus. The study of
      whether the oral fibrosis is part of a systemic spectrum of disease involving
      multiple organs is an interesting pursuit. With this intention the patients
      diagnosed on clinical and histological grounds for OSF were concurrently tested
      by biophysical means for the presence of endomyocardial fibrosis (EMF),
      pancreatic (PF) and retroperitoneal fibrosis (RPF), which are endemic to the area
      studied. Twenty-five (n = 25) cases of OSF who visited the Department of Oral
      pathology & Microbiology. Govt. Dental College, Trivandrum, India for symptomatic
      relief of their illness comprised the study group. Ten (n = 10) age and sex
      matched healthy volunteers comprised the control. All the subjects have had
      undergone cardiologic and gastrointestinal investigations to rule out the
      possibility of concurrent EMF and PF. The patients were all of Indian ethnic
      extraction and mostly (> 90%) were from low socio economic classes. The mean age
      of the patients was 54.16 +/- 14.6 years, including 18 females and 7 males (F:M =
      2.57:1). The severity of fibrosis was unrelated to the age of patients (P >
      0.05). All the patients were chewers of areca quid (12%)/tobacco (88%). In
      addition to quid chewing 3/25 (12%) patients smoked 'bidi' and 6/25 (24%)
      consumed home brewed liquor (arrack/toddy) which contain about 40-50% ethanol.
      Statistically no relationship was observed between the clinical stages of OSF and
      severity of epithelial dysplasia in this study (P > 0.05). Out of the 25
      patients, 5 (20%) showed sclerotic aortic value which may be an age related
      finding. Also 7 (28%) patients were found to be hypertensive and interstitial
      lung disease was present in 2 (8%). The possibility of EMF in one female patient
      who showed thickened RV apical endocardium was ruled out by cardiac
      catheterisation. Thus none of the patients showed evidence of endomyocardial
      fibrosis. The pancreas was found to be hyperchoic in 8(32 1/4) by ultra
      sonography. Liver was found to be hyperchoic in 6 (24%). Fat stain in stool
      samples was found to be positive in 13(58%). The hyperchogenecity of pancreas may
      be due to alcoholism or an underlying endocrine pancreatic insufficiency like
      diabetes and not due to pancreatic fibrosis. The positivity of fat stain could be
      due to fatty liver/alcoholism. Thus the study fails to reveal any evidence of
      pancreatic fibrosis in the group. The lack of any evidence of an associated
      visceral organ fibrosis in OSF made it prudent to believe that this is a loco
      regional disease, initiated by local factors and propagated under their influence
      without systemic involvement.

PMID- 11441805
TI  - [Mystery of fermented foods--There are friendly molds too!].

PMID- 11441806
TI  - Evidence: its meanings in health care and in law. IOM and AHRQ workshop. 10 April
      2000.

PMID- 11441807
TI  - Dope: a love story.

PMID- 11441808
TI  - Structural insight into microtubule function.
AB  - Microtubules are polymers that are essential for, among other functions, cell
      transport and cell division in all eukaryotes. The regulation of the microtubule
      system includes transcription of different tubulin isotypes, folding of
      alpha/beta-tubulin heterodimers, post-translation modification of tubulin, and
      nucleotide-based microtubule dynamics, as well as interaction with numerous
      microtubule-associated proteins that are themselves regulated. The result is the
      precise temporal and spatial pattern of microtubules that is observed throughout
      the cell cycle. The recent high-resolution analysis of the structure of tubulin
      and the microtubule has brought new insight to the study of microtubule function
      and regulation, as well as the mode of action of antimitotic drugs that disrupt
      normal microtubule behavior. The combination of structural, genetic, biochemical,
      and biophysical data should soon give us a fuller understanding of the exquisite
      details in the regulation of the microtubule cytoskeleton.

PMID- 11441809
TI  - Properties and biological activities of thioredoxins.
AB  - The mammalian thioredoxins are a family of small (approximately 12 kDa) redox
      proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in
      turn reduce oxidized cysteine groups on proteins. The two main thioredoxins are
      thioredoxin- 1, a cytosolic and nuclear form, and thioredoxin-2, a mitochondrial
      form. Thioredoxin-1 has been studied more. It performs many biological actions
      including the supply of reducing equivalents to thioredoxin peroxidases and
      ribonucleotide reductase, the regulation of transcription factor activity, and
      the regulation of enzyme activity by heterodimer formation. Thioredoxin-1
      stimulates cell growth and is an inhibitor of apoptosis. Thioredoxins may play a
      role in a variety of human diseases including cancer. An increased level of
      thioredoxin-1 is found in many human tumors, where it is associated with
      aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and
      that have antitumor activity.

PMID- 11441810
TI  - Ribozyme structures and mechanisms.
AB  - The past few years have seen exciting advances in understanding the structure and
      function of catalytic RNA. Crystal structures of several ribozymes have provided
      detailed insight into the folds of RNA molecules. Models of other biologically
      important RNAs have been constructed based on structural, phylogenetic, and
      biochemical data. However, many questions regarding the catalytic mechanisms of
      ribozymes remain. This review compares the structures and possible catalytic
      mechanisms of four small self-cleaving RNAs: the hammerhead, hairpin, hepatitis
      delta virus, and in vitro-selected lead-dependent ribozymes. The organization of
      these small catalysts is contrasted to that of larger ribozymes, such as the
      group I intron.

PMID- 11441812
TI  - Bigger nursing staffs linked with lower hospital pneumonia and UTI rates, HHS
      reports.

PMID- 11441811
TI  - FDA committee gives new antibiotic mixed endorsement.

PMID- 11441813
TI  - Investigation of vCJD cluster points to butchering practices.

PMID- 11441814
TI  - Joe Jelinski, Executive Director, Baton Rouge Technology Council. Interview by
      Leigh Berry.

PMID- 11441815
TI  - Drilling for business with a well-designed Web site.

PMID- 11441816
TI  - Computer technology in dentistry.

PMID- 11441817
TI  - Information fatigue.

PMID- 11441818
TI  - Visual vignette.  Hyperparathyroidism due to a parathyroid adenoma.

PMID- 11441819
TI  - [Total hip arthroplasty in rheumatoid arthritis after reconstruction of
      acetabulum with impacted morsellized bone grafts and a cemented polyethylene cup:
      low incidence of aseptic loosening of the cup].

PMID- 11441820
TI  - Earlier decrease in plasma lipids than increase in C-reactive protein during very
      acute phase of myocardial infarction.

PMID- 11441821
TI  - European Lipoprotein Club: report of the 23rd ELC Annual Conference, Tutzing,
      September 11-14, 2000.

PMID- 11441822
TI  - The cell cycle inhibitor p16(INK4A) sensitizes lymphoblastic leukemia cells to
      apoptosis by physiologic glucocorticoid levels.
AB  - The cyclin-dependent kinase inhibitor p16(INK4A) is frequently inactivated in
      childhood T-cell acute lymphoblastic leukemia. To investigate possible
      consequences of this genetic alteration for tumor development, we conditionally
      expressed p16(INK4A) in the T-cell acute lymphoblastic leukemia line CCRF-CEM,
      which carries a homozygous deletion of this gene. In agreement with its reported
      function, p16(INK4A) expression was associated with hypophosphorylation of the
      retinoblastoma protein pRB and stable cell cycle arrest in G(0)/G(1), documenting
      that the pRB/E2F pathway is functional in these cells. Unexpectedly, p16(INK4A)
      expression increased the sensitivity threshold for glucocorticoid (GC)-induced
      apoptosis from therapeutic to physiologic levels. As a possible explanation for
      this phenomenon, we found that p16(INK4A)-arrested cells had elevated GC receptor
      expression associated with enhanced GC-mediated transcriptional activity and
      increased responsiveness of the GC-regulated cyclin D3 gene. These data are
      supported by our previous findings that GC receptor levels critically influence
      GC sensitivity and imply that p16(INK4A) inactivation, in addition to allowing
      unrestricted proliferation, represents a mechanism by which lymphoid tumor cells
      might escape cell death triggered by endogenous GC.

PMID- 11441823
TI  - Influenza virus-induced AP-1-dependent gene expression requires activation of the
      JNK signaling pathway.
AB  - Influenza A virus infection of cells results in the induction of a variety of
      antiviral cytokines, including those that are regulated by transcription factors
      of the activating protein-1 (AP-1) family. Here we show that influenza virus
      infection induces AP-1-dependent gene expression in productively infected cells
      but not in cells that do not support viral replication. Among the AP-1 factors
      identified to bind to their cognate DNA element during viral infections of Madin
      Darby canine kidney and U937 cells are those that are regulated via
      phosphorylation by JNKs. Accordingly, we observed that induction of AP-1
      dependent gene expression correlates with a strong activation of JNK in
      permissive cells, which appears to be caused by viral RNA accumulation during
      replication. Blockade of JNK signaling at several levels of the cascade by
      transient expression of dominant negative kinase mutants and inhibitory proteins
      resulted in inhibition of virus-induced JNK activation, reduced AP-1 activity,
      and impaired transactivation of the IFN-beta promoter. Virus yields from
      transfected and infected cells in which JNK signaling was inhibited were higher
      compared with the levels from control cells. Therefore, we conclude that virus
      induced activation of JNK and AP-1 is part of the innate antiviral response of
      the cell.

PMID- 11441824
TI  - Vancomycin resistance plasmid in Enterococcus faecalis that encodes sensitivity
      to a sex pheromone also produced by Staphylococcus aureus.

PMID- 11441825
TI  - Inhibitor-resistant TEM-33 beta-lactamase in a Shigella sonnei isolate.

PMID- 11441826
TI  - Update on rifampin resistance in the Legionellaceae.

PMID- 11441827
TI  - Levofloxacin-resistant Streptococcus pneumoniae: second look.

PMID- 11441828
TI  - American Institute of Ultrasound in Medicine 45th annual convention. March 11-14,
      2001. Abstracts.

PMID- 11441829
TI  - Sensitivity of CT scout radiography and abdominal radiography for revealing
      ureteral calculi on helical CT: implications for radiologic follow-up.

PMID- 11441830
TI  - Gonadal and sexual function in men treated for childhood cancer.

PMID- 11441831
TI  - Pathology for the 21st century. 85th Meeting of the German Society of Pathology.
      Munster, Germany, 6-9 June 2000. Abstracts.

PMID- 11441832
TI  - Is asthma a risk factor for dental caries? Finding from a cohort study.
AB  - It has been suggested that asthmatic children may have a higher caries risk, both
      as a result of their medical condition and the physical and physiological effects
      of their pharmacotherapy. By examining the association over time between asthma
      and caries increment, this study tested the hypothesis that childhood asthma is
      associated with an increased caries increment. In a long-standing New Zealand
      cohort study, participants' long-term asthma histories and the 3-year net caries
      increment between the ages of 15 and 18 years were examined. Of the 781 who were
      examined at 15 and 18 years, 39 participants were consistently taking anti-asthma
      medication at the ages of 9, 11, 13 and 15 years (and were labelled in this study
      as 'medication-determined asthmatics'), 56 were identified as consistent wheezers
      at the ages of 9, 11, 13 and 15 years ('wheeze-determined asthmatics') and 36
      were members of both groups. A smaller group (n = 9) was identified as being very
      long-term asthmatics (asthma at 5 years of age and at the ages of 9, 11, 13 and
      15 years). Some 206 study members were identified as having no history of asthma,
      asthma medication or significant wheeze at any time up to and including 18 years.
      The overall mean net caries increment between the ages of 15 and 18 years was
      2.06 surfaces (SD, 3.76). There were no significant differences in caries
      increment between the 206 asthma-free participants and any of the asthma groups.
      This study provides little evidence for an asthma-caries causative relationship.

PMID- 11441833
TI  - Effect of selection for increased body weight in turkeys on lymphoid organ
      weights, phagocytosis, and antibody responses to fowl cholera and Newcastle
      disease-inactivated vaccines.
AB  - The influence of selection was studied for increased 16-wk BW in turkeys on in
      vivo phagocytic activity, antibody responses to vaccines, and weight of the
      spleen and bursa of Fabricius. A line (F) of turkeys selected long term for
      increased 16-wk BW and its corresponding randombred control (RBC2) were compared.
      Phagocytic activity was evaluated by the carbon clearance assay. Antibody
      responses to inactivated Newcastle disease virus and Pasteurella multocida
      vaccines were examined by ELISA. Body weight and relative weights of spleen and
      bursa of Fabricius of the two lines were also compared. The F line had lower
      phagocytic activity than the RBC2 line (P < 0.05). In addition, the F line had
      greater BW, relative weight of spleen, and ratio of spleen to bursa of Fabricius
      weight (P < 0.01) but had a lower relative weight of bursa of Fabricius at 9 wk
      of age. However, there were no line differences in the antibody responses to
      Newcastle disease virus or P. multocida vaccines at 1, 2, 3, 4, 5, or 12 wk after
      vaccination. Based on the present results, it is suggested that long-term
      selection for increased 16-wk BW might have resulted in changes in the immune
      system, as indicated by changes in the relative weights of the spleen and bursa
      of Fabricius and phagocytic activity. The decreased phagocytic activity in the F
      line may be partially responsible for increased susceptibility to specific
      diseases in this line.

PMID- 11441834
TI  - Genotype-by-environment interaction with broiler genotypes differing in growth
      rate. 1. The effects of high ambient temperature and naked-neck genotype on lines
      differing in genetic background.
AB  - High ambient temperature (AT) significantly depresses growth rate and meat yield
      of commercial broilers, thus making it a major factor hindering poultry meat
      production, especially in hot climates. The effects of high AT were variably
      moderated when feather coverage was reduced by the naked-neck gene (Na). In this
      study, the effects of high AT and Na were investigated in broiler progeny of hens
      from a sire line and two dam lines, differing in growth rate and meat yield due
      to different breeding histories. Heterozygous naked-neck (Na/na) males were mated
      with normally feathered (na/na) hens from the three lines. The 500 progeny were
      segregated for Na/na and na/na genotypes. After brooding, chicks of each maternal
      background, Na genotype, and sex were equally divided to two similar chambers and
      were reared on litter to 53 d of age. One chamber was set to normal AT, averaging
      25 C; the second chamber was set to high AT, averaging 30 C. The high AT
      treatment reduced growth and meat yield in the progeny of all three groups. This
      reduction increased with age and was highest in the broilers produced by hens
      from a sire line bred for high growth rate and breast meat yield. The two other
      groups, produced by hens from selected and relaxed dam lines, differed in growth
      rate but were similarly affected by the high AT. It is suggested that the
      magnitude of the high AT effect depends not only on differences in potential
      growth rate but also on differences in overall genetic background. It was also
      shown that broiler performance in the final weeks could be improved by
      introducing the Na gene into commercial flocks. The advantage of the Na/na
      genotype was much more pronounced at high AT and in broilers with genetically
      higher growth rate and breast meat yield.

PMID- 11441835
TI  - Genetic parameters of reproductive traits in Brown Tsaiya ducks artificially
      inseminated with semen from Muscovy drakes.
AB  - A selection experiment on maximum duration of fertility of Brown Tsaiya ducks
      after artificial insemination (AI) with pooled Muscovy semen has been conducted
      since 1992. The Brown Tsaiya ducks were divided into two lines: a control line
      (T) with no selection and a selected line (S). The traits measured were the
      number of eggs set that were laid from Days 2 to 15 after one AI (NES), the
      number of fertile eggs at candling (NEF), the total number of dead embryos (NED),
      the maximum duration of fertility (MD), and the number of hatched mule ducklings
      (NEH). The selected trait was NEF. Six generations with a total of 2,127 females
      were measured. The variance components were estimated for each line in a multiple
      trait animal model, using the restricted maximum likelihood (REML) methodology,
      which yields estimates free of bias caused by selection and inbreeding. Estimates
      of the heritability and genetic correlation from the two lines were very similar.
      Heritabilities in the S and T lines, respectively, were 0.14 and 0.10 for NES,
      0.30 and 0.26 for NEF, 0.06 and 0.09 for NED, 0.28 and 0.21 for MD, and 0.18 and
      0.19 for NEH. High and favorable genetic correlations existed between NEF and MD
      (0.96 and 0.92), between NEF and NEH (0.86 and 0.91), and between MD and NEH
      (0.90 and 0.82). The results suggested that selection for NEF could improve the
      maximum duration of fertility, but it could be useful to check the estimates of
      genetic parameters in a meat-type female duck.

PMID- 11441836
TI  - Effect of hatch on the distribution for failure of an embryo to survive
      incubation.
AB  - The objectives of this paper were to validate an improved model to describe
      failure to hatch by using data obtained from two hatches of a line of chickens
      and to examine the effect of hatch on the distribution for time of failure of an
      embryo to survive incubation. Breakout analysis of 11,254 eggs that failed to
      hatch was used to characterize the distribution for time of failure to survive
      and the probability of failure to hatch. The distribution for time of failure to
      survive was modeled by a diphasic Weibull distribution, corresponding to the two
      phases of increased embryonic mortality during incubation. Distribution
      parameters for time of failure to survive were estimated by maximum likelihood
      and minimum Hellinger distance. Goodness-of-fit statistics validated the
      appropriateness of the diphasic Weibull distribution. Overall, the proportion of
      infertility was 0.213, and the proportion of embryonic mortality by the end of
      incubation was 0.086. Among embryos that suffered mortality during incubation,
      the proportion that died during Phase 1 was 0.77; therefore, 0.23 died during
      Phase 2. For Phase 1, mean time of mortality was 2.6 d, and standard deviation
      was 3.3 d. For Phase 2, mean time was 17.4 d, and standard deviation was 2.0 d.
      Time of mortality was distributed differently in the two hatches; this difference
      occurred mostly during Phase 1. Failure rates of the two hatches were different
      during the first 3 d of incubation. The model is useful to assess probability of
      failure to hatch and the distribution for time of failure to survive during
      incubation.

PMID- 11441837
TI  - The effect of mannanoligosaccharides, bambermycins, and virginiamycin on
      performance of large white male market turkeys.
AB  - A study was conducted to evaluate the effects of mannanoligosaccharides (MOS),
      bambermycins (BAM), and virginiamycin (VIR) on the growth performance of male
      turkeys. Hybrid Large White male poults were assigned to six dietary treatments:
      control, MOS, BAM, VIR, MOS+BAM (MB), and MOS+VIR (MV). All diets were formulated
      to meet NRC (1994) nutrient requirements. There were eight replicate floor pens
      per treatment with 20 birds per pen reared from 1 to 140 d. Body weight and feed
      conversion (FC) were collected at 3-wk intervals and at 20 wk of age. Mortality
      and culled birds were recorded daily. All treatments except MV significantly (P <
      0.05) increased 20 wk BW. Body weight was increased at 12 wk by BAM, whereas VIR
      increased BW at Weeks 12 and 15. All treatments improved FC for Weeks 0 to 3,
      whereas VIR, MB, and MV improved FC for Weeks 0 to 12 and 0 to 18. There were no
      treatment effects on cumulative mortality or cull rate. Dietary supplemental MOS,
      BAM, and VIR resulted in improved growth performance of Large White turkeys.
      These results indicate that MOS may be utilized as an alternative to antibiotic
      growth promotants to improve turkey performance.

PMID- 11441838
TI  - Air velocity alters broiler performance under harsh environmental conditions.
AB  - The effect of air velocity (AV) on weight gain, feed intake, and feed efficiency
      was studied in male broiler chickens exposed to a constant 35 C, 60% RH, and
      continuous illumination from 4 through 7 wk of age. In two separate trials, AV of
      0.5, 1.5, 2.0, and 3.0 m/s (Trial 1) and 1.0, 1.5, 2.0, and 2.5 m/s (Trial 2)
      were used. The fifth week was used for acclimation to the targeted environmental
      conditions. Weight gain was significantly higher in broilers exposed to AV of 1.5
      and 2.0 m/s in both trials, which coincided with significantly higher feed intake
      and feed efficiency. Exposure to the low AV (0.5 and 1.0 m/s) resulted in weight
      gain, feed intake, and feed efficiency that were less than those of broilers
      exposed to high AV (2.5 and 3.0 m/s). In all treatments, broilers developed
      hyperthermia, but there were no significant differences in body temperature (Tb)
      among the birds. It can be concluded that AV has a significant effect on broiler
      performance; the optimal AV was found to be 1.5 to 2.0 m/s.

PMID- 11441839
TI  - Efficacy of N-acetylcysteine to reduce the effects of aflatoxin B1 intoxication
      in broiler chickens.
AB  - N-acetylcysteine (NAC) has been used safely in humans and in other mammals as an
      antidote against several toxic and carcinogenic agents, including aflatoxin B1
      (AFB1). The aim of this study was to evaluate the capability of dietary
      supplementation with NAC to ameliorate the effects of subacute intoxication with
      AFB1 in broiler chickens. One hundred twenty male Hubbard 1-d-old chickens were
      allocated into one of four dietary treatments: 1) control group without
      treatment, 2) purified AFB1 added to diet (3 mg/kg of feed) for 21 d, 3) NAC (800
      mg/kg BW, daily), or 4) AFB1 plus NAC at the same doses as Groups 2 and 3.
      Broilers treated with AFB1 plus NAC were shown to be partially protected against
      deleterious effects on BW (57.8%), daily weight gain (49.1%), feed conversion
      index (21.4%), plasma and hepatic total protein concentration (45.2, 66.7%),
      plasma alanine aminotransferase (67.4%), hepatic glutathione-S-transferase
      (18.8%), and reduced glutathione liver concentration (75.0%). In addition, they
      showed less intense liver fading, friable texture, and microvesicular steatosis.
      In the kidney, thickening of glomerular basement membrane was also less severe in
      NAC+AFB1-treated chickens than in AFB1-treated chickens. Our results suggest that
      NAC provided protection against negative effects on performance, liver and renal
      damage, and biochemical alterations induced by AFB1 in broiler chickens. Effects
      of NAC alone on chick performance were also evaluated. Addition of NAC to diet
      (800 mg/kg BW) did not negatively affect feed consumption, conversion index, or
      serum chemistry and did not induce structural changes in the liver or kidney.

PMID- 11441840
TI  - Influence of dietary phytase supplementation on incidence and severity in
      broilers divergently selected for tibial dyschondroplasia.
AB  - A study was conducted to determine the effect of dietary supplementation of
      phytase on the incidence and severity of tibial dyschondroplasia (TD) in chickens
      selected for high (HTD) and low (LTD) incidences of TD for 11 generations. By
      feeding a phosphorus-deficient diet (0.1% nonphytate phosphorous; nPP), HTD and
      LTD chickens were further identified as high-sensitivity birds (HS) and low
      sensitivity birds (LS) to phosphorus deficiency based on mortality. Two hundred
      forty 1-d-old chicks from HTD and LTD lines (five replications of four birds per
      treatment) were randomly assigned to a control diet with 0.5% nPP and two
      treatment diets (0.1% nPP) with and without 600 phytase units (FTU) Natuphos
      phytase/kg. Feed consumption and growth rate were measured for 3 wk, and both
      tibiae were scored for TD incidence, average TD score, and total number of TD
      lesions with the most severe form of the abnormality (lesions that were scored
      3). The addition of phytase had no influence on TD incidence and lesion scores of
      3 in HTD chicks. However, a nonsignificant reduction in TD incidence (P = 0.07),
      TD score, and no. 3 lesions (P < or = 0.01) were observed in LTD chicks.
      Interactions between sensitivity (to P deficiency) and phytase (P < or = 0.01)
      and sensitivity and nPP (P < or = 0.01) were observed for no. 3 scores in LTD
      chicks. These results indicate that phytase was effective in reducing TD
      incidence and severity in LTD chicks but not in HTD chicks.

PMID- 11441841
TI  - n-3 enrichment of chicken meat. 1. Use of very long-chain fatty acids in chicken
      diets and their influence on meat quality: fish oil.
AB  - We assessed the effect of a diet supplemented with fish oil (FO) on the
      performance, fatty acid (FA) composition, quality, and sensory traits of broiler
      meat. Diets enriched with 0, 2, or 4% FO plus tallow (T) up to 8% added fat (T1,
      T2, and T3, respectively) were given to the birds throughout a 38-d growth
      period. T3 was replaced by a mixture of FO, linseed oil (LO), and T (1, 3, and 4%
      respectively) for 1 wk (T4) or 2 wk (T5) before slaughter. Meat quality, taste,
      and FA profile were determined. Higher final weights were recorded for birds fed
      T3, although feed efficiency was not affected. Other performance or objective
      meat quality parameters did not show significant differences among treatments.
      High FO concentrations decreased the saturated and monoenoic FA contents in the
      thigh samples. The amount of polyunsaturated fatty acids (PUFA) increased when
      added to the diet (FO diets), mainly as long-chain n-3 FA [eicosapentaenoic fatty
      acid (EPA), docosapentaenoic fatty acid (DPA), and docosahexaenoic fatty acid
      (DHA)]. On the other hand, levels of total n-6 FA resulted in slight changes,
      mostly in linoleic acid (LA). By replacing the FO diet with the experimental
      mixture (T4, T5), the n-3 and n-6 FA contents increased, mainly in the form of
      linolenic acid and LA, respectively, only 1 wk later. After 1 wk of T4, the DHA
      levels in chicken decreased. Sensory panelists could not identify the meats from
      T4 and T5 as being different from the control diet (T1).

PMID- 11441842
TI  - n-3 enrichment of chicken meat. 2. Use of precursors of long-chain
      polyunsaturated fatty acids: linseed oil.
AB  - To assess the effect of supplying linseed oil (LO) in the diet on performance,
      fatty acid (FA) composition, and quality objective parameters of broiler meat,
      diets enriched with 0, 2, or 4% LO plus tallow (T) up to 8% added fat (T1, T2,
      and T3, respectively) were given to broiler chickens throughout a 38-d growth
      period. T3 birds were slaughtered at 24 or at 52 d of age to study the effect of
      feeding time on FA accumulation in tissue. Objective and subjective evaluations
      of meat quality were performed on samples from 38-d-old birds, and the FA
      profiles of thigh and liver samples were determined. Performance parameters
      showed little difference between treatments. The differences in carcass yield
      values or in the objective quality parameters of the meat between treatments were
      not significant. Increased levels of LO clearly decreased the saturated (SAT) and
      monounsaturated FA (MUFA) contents. LO increased the amount of polyunsaturated FA
      (PUFA), mainly because of the linolenic (LNA) and linoleic (LA) acid content in
      the T3 samples, but they hardly reflected the wide range given in the
      experimental diets. The n-3 long-chain (LC) PUFA content of T3 thighs was
      slightly higher than in T1 thighs. Unexpectedly, longer feeding time of LO diets
      did not result in peripheral tissue accumulation of n-3 LC-PUFA, although
      chickens could convert LNA to longer-chain metabolites in liver at 24 d of age.

PMID- 11441843
TI  - The performance of broiler chicks fed diets containing extruded cottonseed meal
      supplemented with lysine.
AB  - Three experiments were conducted to test the hypothesis that extruding cottonseed
      meal (CSM) with supplemental lysine improves its feeding value by detoxifying
      gossypol. The performance of 1-wk-old straight-run Peterson x Arbor Acres broiler
      chicks fed diets containing 20% feed-grade or extruded CSM was compared with that
      of control chicks fed corn and soybean meal-based broiler rations. All diets were
      formulated to meet minimum NRC requirements. Lysine levels were adjusted by
      addition of synthetic lysine at rates of 0.5 to 2.0% of the protein in CSM. In
      all experiments, weight gain, feed intake, and feed conversion ratio (FCR) of
      broilers at 21 d were significantly affected by the diets. Feeding feed-grade and
      extruded CSM resulted in decreased body weight gain, increased feed intake, and
      inefficient feed utilization. When 2% lysine was added to feed-grade or extruded
      CSM, the body weight gains of chicks were not significantly different from those
      fed the control diet. The FCR of chicks fed feed-grade and extruded CSM plus 2%
      lysine at 21 d was significantly better than that of chicks fed feed-grade or
      extruded CSM alone. Abdominal fat pads (as a percentage of body weight) were
      significantly increased by the inclusion of CSM with or without the addition of
      lysine (P < or = 0.019). Liver, spleen, and heart weights were not affected by
      the presence of 20% CSM in the diet. The effects of CSM on plasma iron level was
      not consistent. Only in Experiment 1 did CSM cause a significant reduction in
      plasma iron. The hemoglobin contents and hematocrit values of blood from chicks
      fed diets with 20% CSM were not significantly different from those of the
      controls. The extrusion process reduced the free gossypol in CSM, but the total
      gossypol level was not changed, and chick performance was not improved. However,
      this study shows that, with adequate supplemental lysine, CSM can be used in
      broiler diets without a reduction in performance.

PMID- 11441844
TI  - Influence of cage density and prior dietary phosphorus level on phosphorus
      requirement of commercial leghorns.
AB  - Two studies were conducted to determine whether cage density and prior dietary
      nonphytate P (NPP) level affect hens' P requirements. In Experiment 1, hens were
      housed at three cage densities (300, 400, and 600 cm2 or 46.5, 62.0, and 93.0
      inches2/hen) and fed four levels of NPP (0.15, 0.25, 0.35, and 0.40%) for 6 wk to
      determine the effect of cage density on the P requirement. Egg production (EP),
      feed consumption (FC), egg weight (EW), and egg specific gravity (ESG) were
      measured to evaluate performance. Cage density influenced EP within Week 1 (P <
      0.01), and during Weeks 5 and 6, there was a cage density x NPP-level interaction
      (P < 0.05). At 300 cm2, EP was more severely affected by 0.15 and 0.25% NPP than
      at 400 and 600 cm2. A linear decrease (P < 0.001) in FC was observed because of
      decreased NPP. Hens at 300 cm2 consumed 4 g less feed/hen per d than hens at 400
      cm2. A linear decrease in EW was observed as the NPP level decreased (P < 0.01)
      from 0.25 to 0.15%, and there was no effect of cage density. Experiment 2 was
      conducted to determine the effect of prior dietary P levels on time required to
      create a P deficiency. Hens fed 0.4% NPP were divided into two groups and fed
      0.25 and 0.4% NPP for 4 wk. At the end of 4 wk, hens fed 0.25% NPP were further
      divided into three groups and were fed diets containing 0.09, 0.25, and 0.30% NPP
      for an additional 6 wk. Hens fed 0.4% NPP were divided into three groups and fed
      diets containing 0.09, 0.4, and 0.45% NPP. Reduction of NPP from 0.4 and 0.25% to
      0.09% reduced EP by 8.5 and 6.8%, respectively, within 3 wk. Prior NPP levels had
      no influence on time required to create a P deficiency in terms of EP. Reduction
      of NPP from 0.4 and 0.25% to 0.09% reduced (P < 0.05) FC. A decline in FC
      occurred 2 wk earlier in hens previously fed 0.4% than those fed 0.25% NPP. This
      result indicates that hens fed 0.4% NPP became P deficient more quickly than hens
      fed 0.25%. We concluded that cage density and prior NPP level affect the hen P
      requirements or time required to create a P deficiency.

PMID- 11441845
TI  - Enterocyte dynamics and mucosal development in the posthatch chick.
AB  - Changes in the morphology of the small intestinal mucosa and enterocyte dynamics
      were examined in posthatch chicks through 12 d. At hatch, enterocytes were round
      and nonpolar; however, within 24 h posthatch, enterocytes lengthened and
      exhibited more typical morphology. Crypts were rudimentary at hatch and by 48 h
      invagination was completed and crypt numbers increased by branching and fission,
      with the number of crypts per villus reaching plateau after 72 h posthatch. All
      epithelial cells were proliferative at hatch. In the crypts, the proportion of
      proliferating enterocytes decreased to 50 to 60% within 2 d posthatch, whereas
      along the villus the proportion of proliferating cells decreased to 10 to 20% by
      6 d. Different patterns of temporal development of villi were observed in the
      duodenum, jejunum and ileum. Individual villus surface area increased steadily in
      the duodenum throughout the experiment, whereas individual jejunal and ileal
      villus surface areas increased more slowly after 4 d posthatch. The number of
      villi per cross-section of intestine increased in the duodenum and jejunum but
      not in the ileum. The total segment villus surface area increased similarly in
      all segments until 3 d posthatch, after which the jejunum increased considerably
      in absorptive area, whereas the duodenum and ileum increased more slowly. This
      study shows that, in the hatching chick, the small intestine matures in a manner
      similar to neonatal mammals, with specific ontogenetic timetables in the
      different small intestinal segments, however, the most dramatic changes occur
      within the first 24 h posthatch.

PMID- 11441846
TI  - The effect of citric acid on the calcium and phosphorus requirements of chicks
      fed corn-soybean meal diets.
AB  - Data previously reported from our laboratory indicated that supplementation of a
      corn-soybean meal diet with citric acid improves P utilization in chicks. The
      four experiments reported herein were conducted to further evaluate the effects
      of citric acid on Ca and P utilization for chicks fed a corn-soybean meal diet.
      Diets in all experiments were fed to chicks from 8 to 21 or 22 d of age. The
      first experiment evaluated the effect of 6% citric acid on the Ca requirement of
      chicks. A Ca-deficient basal diet [23% CP, 0.54% Ca, 0.45% available P (AP)]
      containing 0 to 0.7% supplemental Ca in 0.1% increments was fed with or without
      6% citric acid. The results indicated that citric acid did not significantly
      affect the Ca requirement. A second experiment evaluated different levels of
      citric acid (0, 2, 4, or 6%) on P utilization, and results indicated that 4 and
      6% citric acid produced the largest responses in growth and tibia ash.
      Experiments 3 and 4 were then conducted to determine whether 4 or 6% citric acid
      would reduce the level of supplemental P required. Dietary treatments were a P
      deficient basal diet (23% CP, 1.0 or 1.3% Ca, 0.20% AP) supplemented with 0 to
      0.25% inorganic P with or without 4 or 6% citric acid. When diets contained
      citric acid, weight gain and tibia ash were maximized at lower AP levels than
      when diets contained no citric acid. The results of this study indicate that
      citric acid increases P utilization in corn-soybean meal diets and reduces the AP
      requirement by approximately 0.10% of the diet.

PMID- 11441847
TI  - Use of expander cottonseed meal in broiler diets formulated on a digestible amino
      acid basis.
AB  - This experiment was designed to evaluate the use of expander cottonseed meal
      (CSM) in broiler diets formulated on a digestible amino acid basis and to
      determine the tissue distribution of gossypol enantiomers and their relationship
      to gossypol consumption. Gossypol is an antinutritional polyphenolic pigment
      found in cottonseed. A total of 800 1-d-old broilers (Arbor Acres) was randomly
      divided into 40 groups of 20 birds each and placed in a broiler house with wood
      shavings litter. The CSM was included in starter and grower diets at 0, 7, 14,
      21, and 28% of the diet. Diets were formulated to have similar levels of
      digestible methionine and lysine as the 0% CSM control diet. At 21 d of age, five
      birds per pen were randomly selected for the determination of gossypol
      enantiomers in plasma, liver, heart, and breast muscle. Tissues were again
      collected at 42 d of age. Results of this experiment indicated that at 21 d of
      age cumulative body weight and feed-to-BW ratios of birds fed CSM diets were not
      significantly different from the control. By 35 d of age, feed-to-BW ratios of
      experimental birds fed the 28% CSM diet were significantly greater than the
      control birds, and by 42 d, BW were lower than those of the control group. Tissue
      concentrations of total, (+) and (-) gossypol increased linearly as the level of
      CSM increased. At 42 d, liver had the most gossypol with a ratio of 87% (+)
      gossypol to 13% (-) gossypol. Plasma contained 73% (+) gossypol and 27% (-)
      gossypol. Heart contained 45% (+) gossypol and 55% (-) gossypol. Breast muscle
      had the least gossypol. Results of this experiment indicated that expander
      solvent CSM could be fed to broilers at up to 21% of the total diet if amino acid
      digestibility was considered.

PMID- 11441848
TI  - Steroid hormones during embryonic development in Japanese quail: plasma, gonadal,
      and adrenal levels.
AB  - The purpose of this experiment was to measure plasma, gonad, and adrenal steroid
      hormones during embryonic and early posthatch development in Japanese quail.
      Blood plasma samples were collected from male and female Japanese quail embryos
      at 2-d intervals between Day 10 of incubation and Day 5 posthatch. Gonads and
      adrenal glands were collected from a separate set of embryos at the same ages.
      Concentrations of androgen (testosterone and 5alpha-dihydrotestosterone) and
      17beta-estradiol (E2) were determined by RIA. Plasma androgen changed
      significantly (P < 0.001) with age in males and females, and there were
      significant differences (P < 0.001) between sexes in the hormonal patterns. Males
      had higher plasma androgen than females; conversely, females consistently had
      overall higher levels of estradiol than males. Adrenal gland steroid content
      remained relatively high and did not change significantly with age. In contrast,
      steroid content of gonads followed patterns similar to those observed for plasma
      levels. These results provide evidence for steroid hormone production by the
      gonads of both sexes, as well as for distinct differences in the patterns
      observed in the adrenal gland and gonads. These results provide evidence for
      gonadal regulation of changes in circulating hormone levels. Further, these
      hormonal patterns were associated with the timing of steroid-induced sexual
      differentiation in the Japanese quail, suggesting that plasma gonadal steroids
      are critical in sexual differentiation.

PMID- 11441849
TI  - Influence of dietary fat source, alpha-tocopherol, and ascorbic acid
      supplementation on sensory quality of dark chicken meat.
AB  - We studied the influence of dietary fat source and dl-alpha-tocopheryl acetate
      and ascorbic acid supplementation on the sensory quality of cooked dark chicken
      meat stored at -20 C for different periods. Results showed that dietary fat
      source and alpha-tocopheryl acetate supplementation influenced sensory scores
      (rancid flavor and aroma and acceptability). Ascorbic acid had no influence on
      these scores. Thiobarbituric acid values showed a high correlation with sensory
      scores. In addition, the low levels of alpha-tocopheryl acetate contained in the
      trace mineral-vitamin mix (20 IU/kg of feed) were enough to prevent rancidity
      development in cooked dark chicken meat when broilers were fed a saturated fat
      diet and samples were vacuum-packed and stored at -20 C for 13 mo.

PMID- 11441850
TI  - Influence of age and postchill carcass aging duration on chicken breast fillet
      quality.
AB  - Breast fillet quality was evaluated from 37-, 39-, 42-, 44-, 46-, 49-, and 51-d
      old broilers after post-chill (PC) aging of the carcass 0, 2, 4, or 6 h and
      deboning. Fillets were vacuum sealed in cooking bags and heated to an internal
      temperature of 72 C by submersion in a 95 C water bath. Cook yield was determined
      as the weight percentage of the fillet remaining after cooking. Texture of the
      cooked fillets was measured using a Warner-Bratzler (W-B) shear device. Fillet
      cook yield and shear force values were significantly affected by bird age at
      slaughter, and PC carcass aging duration before deboning. Bird gender
      significantly affected cook yield, whereas the interaction between age and PC
      aging duration significantly affected W-B shear. Fluid lost during cooking was
      greater for fillets aged 0 h PC and decreased when PC aging was 2 h or greater.
      Overall, W-B shear values decreased (more tender) when fillets were aged on the
      carcass at least 2 h PC, with the exception of fillets from 51-d-old broilers.
      After 2 h of PC aging on the carcass, shear force values for fillets from older
      broilers (49- and 51-d-old) were in the "very tough" portion of a texture scale
      (>12.60 kg), whereas textures of fillets from 42- and 44-d-old broilers were in
      the "slightly tough to slightly tender" portion of the scale (8.5 and 7.2 kg,
      respectively). These data show that if poultry processors harvest fillets earlier
      than usual (<2 h PC aging), the fillet texture will be more tender if it
      originates from younger broilers (42- or 44-d-old) instead of older broilers (49-
      or 51-d-old).

PMID- 11441851
TI  - Cooling rate effect on outgrowth of Clostridium perfringens in cooked, ready-to
      eat turkey breast roasts.
AB  - The potential for Clostridium perfringens spores to germinate and grow in cooked,
      ready-to-eat turkey products was evaluated to determine a safe cooling rate
      within the critical temperatures of 48.9 C (120 F) through 12.8 C (55 F). Raw
      turkey deli breast roasts were inoculated with a cocktail of C. perfringens
      spores (NCTC 8238, NCTC 8239, and NCTC 10388) and cooked in a steam oven to an
      internal temperature of 72 C. The sample roasts were then cooled through the
      critical cooling range at rates yielding cooling times of 6, 8, and 10 h. Turkey
      roasts were analyzed for spore growth and multiplication using tryptose-sulfite
      cycloserine agar and anaerobic incubation at 37 C for 48 h. Cooling times of 6
      and 8 h showed no proliferation of C. perfringens that would violate the
      USDA/Food Safety Inspection Service safe cooling standard criteria, which would
      allow no more than a 1 log10 multiplication between 48.9 and 12.8 C. A 9.6-h
      cooling period between the designated temperatures at a 95% confidence interval
      was determined to be adequate for nonproliferation of C. perfringens. On the
      other hand, a 95% tolerance interval would be more stringent in that it suggests
      no more than an 8.9-h cooling period. Tolerance intervals required that 95% of
      all our observations did not exceed the limit of 1 log10 increase in C.
      perfringens. This study indicated that in cooked, ready-to-eat turkey deli
      breasts, a cooling period between 48.9 C (120 F) and 12.8 C (55 F) of no greater
      than 8.9 h should be utilized to prevent possible C. perfringens foodborne
      outbreaks.

PMID- 11441852
TI  - The effect of transportation stress on excretion rates of campylobacters in
      market-age broilers.
AB  - We determined the effects of transportation distance and holding times at a
      commercial slaughter facility on excretion rates of Campylobacter spp. in
      broilers. Fecal samples from broilers in each of 10 flocks were obtained at the
      following three sampling points: at the farms, following transportation, and
      after holding at the plant. The farms examined were divided into two groups based
      on distances and transport times to the plant. The prevalence and levels of
      Campylobacter spp. were evaluated for all specimens taken at the three sampling
      points. A statistically significant increase in counts was observed in samples
      from both groups following transportation (P < 0.05). The resting period at the
      abattoir prior to slaughter did not significantly reduce rates of Campylobacter
      spp. shedding in the flocks examined. Differences in distance travelled and
      transport durations between the two groups was not found to be a statistically
      significant factor in altering excretion rates of the organism. The present study
      demonstrated that transport-induced stress increased shedding of Campylobacter
      spp. in fecal material of broilers that may subsequently result in extensive
      carcass contamination.

PMID- 11441853
TI  - The effect of shell egg pasteurization on the protein quality of albumen.
AB  - The effect of a low-temperature, extended-time, in-shell pasteurization process
      on the protein quality of egg albumen was evaluated. Ten dozen fresh chicken eggs
      were pasteurized in a hot-air oven at 55 C for 180 min. The eggs were
      refrigerated and broken out for analysis on Days 0, 7, 14, 28, 42, and 56
      following pasteurization. There were no significant differences in total or
      soluble protein over the experimental period for the pasteurized or unpasteurized
      albumen. Mean protein content was 80.6 +/- 0.5% for the pasteurized albumen and
      80.9 +/- 0.5% for the unpasteurized albumen. In vitro digestibility, as measured
      by the AOAC method, was 82.4 +/- 0.7% for the pasteurized albumen and 81.7 +/-
      0.6% for the unpasteurized albumen. There were no significant differences over
      the experimental period in the digestibility of the samples. Free amino acids and
      discriminant-computed protein efficiency ratio (DC-PER) also did not differ
      between the pasteurized and unpasteurized albumens or over the experimental
      period. The in-shell pasteurization process used had no effect on the protein
      quality of albumen.

PMID- 11441854
TI  - Detection of Campylobacter spp. in ceca and crops with and without enrichment.
AB  - The purpose of this experiment was to determine how sampling method (direct
      plating or enrichment) affected the rate of Campylobacter spp. isolation from
      crop and cecal samples. In four separate trials, 32 New York-dressed broiler
      carcasses were obtained from commercial plants (n = 128). Crops and ceca were
      removed aseptically, direct plated, and enriched. Samples were direct-plated on
      Campy-Cefex plates that were incubated at 42 C for 36 to 48 h under a
      microaerobic atmosphere (5% O2, 10% CO2, 85% N2). After direct plating, samples
      were enriched in Bolton broth at 37 C for 4 h and 42 C for 20 h under a
      microaerobic atmosphere before plating onto Campy-Cefex plates. Campylobacter
      spp. was detected in 95.3% of direct-plated crop samples and 99.2% of enriched
      crop samples. Campylobacter spp. was detected in 100% of direct-plated cecal
      samples and 63.3% of enriched cecal samples. All 128 crop and cecal samples were
      positive for the organism by one or both methods. Mean counts of Campylobacter
      spp. were 3.6 log10 cfu/g of crop sample and 6.8 log10 cfu/g of cecal sample. For
      these two sample types, both of which tend to be contaminated with many viable
      cells, direct plating is sufficient for isolation of Campylobacter. Direct
      plating also provides an estimate of contamination level. Enrichment of cecal
      samples resulted in a decreased rate of detection and did not allow estimation of
      numbers of Campylobacter. The large numbers of non-Campylobacter species that
      inhabit the intestinal tract may out-compete Campylobacter during enrichment,
      confounding detection.

PMID- 11441855
TI  - [Cancer: what does the future bring?].

PMID- 11441856
TI  - Hyperbaric oxygenation for cerebral palsy.

PMID- 11441857
TI  - Hyperbaric oxygenation for cerebral palsy.

PMID- 11441858
TI  - Hyperbaric oxygenation for cerebral palsy.

PMID- 11441859
TI  - Sentinel node biopsy in breast cancer.

PMID- 11441861
TI  - Trafficking of lacrimal aquaporin-5 in Sjogren's syndrome.

PMID- 11441863
TI  - Helicobacter pylori: the story continues.

PMID- 11441864
TI  - Helicobacter pylori: the story continues.

PMID- 11441865
TI  - Thyroid function tests.

PMID- 11441866
TI  - Thyroid function tests.

PMID- 11441867
TI  - Thyroid function tests.

PMID- 11441868
TI  - Risk of colorectal cancer after breast cancer.

PMID- 11441869
TI  - Changes in ife expectancy in Russia.

PMID- 11441870
TI  - The fourth disease, 1900-1881, RIP.

PMID- 11441871
TI  - Context and health outcomes.

PMID- 11441873
TI  - [A 68-year-old man with speech disturbance as the initial symptom followed by
      bradykinesia and dementia.  Clinical conference].
AB  - We report a 68-year-old man with progressive speech disturbance and dementia. He
      was well until 1995, when he noted an onset of difficulty in speech. He was able
      to name simple objects and understand language, however, he showed great
      difficulty in spontaneous speech. In 1998, he visited our service. He was alert
      and oriented, but he showed moderate degree of dementia. He did not appear to
      have aphasia but he showed marked dysarthria and slurred speech. He showed limb
      kinetic apraxia in his right hand. He showed moderate restriction in his vertical
      gaze, masked face, and dysphagia. He walked normally. No rigidity, ataxia, or
      abnormal involuntary movement was noted. He showed grasp response and he was
      bradykinetic. He was treated with levodopa without effect. His condition
      deteriorated slowly and he was admitted to our service because of fever on
      February 13, 1999. He was alert but almost mute. He was unable to look upward or
      downward. Oculocephalic response was preserved. Axial rigidity was noted but no
      limb rigidity was present. He walked with small steps. Retropulsion was present.
      Deep tendon reflexes were diminished and the plantar response was flexor
      bilaterally. Laboratory examinations were unremarkable and his fever went down
      within a few days by supportive treatment. He was discharged to his home, where
      his condition deteriorated further. He developed cardiopulmonary arrest on May 3,
      1999 and was brought into ER again. Cardiopulmonary resuscitation was
      unsuccessful and he was pronounced dead at 7:30 in the morning on the same day.
      The patient was discussed in a neurological CPC. The chief discussant arrived at
      the conclusion that this patient had corticobasal degeneration. But he felt that
      the differential diagnosis from atypical progressive supranuclear palsy, in which
      cortical pathology and symptoms predominated as in corticobasal degeneration,
      would be extremely difficult. Most of the participants felt that this patient had
      corticobasal degeneration, but a few thought that he had atypical PSP. Post
      mortem examination revealed asymmetric cortical atrophy, which was accentuated in
      the left motor cortical area. Microscopic examination of the precentral cortex
      revealed neuronal loss and gliosis. Ballooned neurons and astrocytic plaques were
      also seen. The substantia nigra showed marked neuronal loss. Neuropil threads
      were observed in the nigra. Those threads were positive for anti-tau
      immunohistochemistry. The internal segment of the globus pallidus, the
      subthalamic nucleus, and the cerebellar dentate nucleus showed mild to moderate
      neuronal loss. A few neurofibrillary tangle-positive neurons were seen in these
      structures. Neuropil threads were also seen throughout. Pathologic changes were
      consistent with the diagnosis of corticobasal degeneration. One of the
      participants pointed out that he was able to walk at the time when he was showing
      marked speech disturbance and limb-kinetic apraxia, which was rather unusual for
      PSP suggesting corticobasal degeneration.

PMID- 11441875
TI  - Current world literature. Gastrointestinal tract.

PMID- 11441874
TI  - Current world literature. Sarcomas.

PMID- 11441876
TI  - Current world literature. Supportive care.

PMID- 11441877
TI  - South Africa in crisis on HIV/AIDS treatment.

PMID- 11441878
TI  - DOE's support of the Sloan Digital Sky Survey.

PMID- 11441879
TI  - The biology of music.

PMID- 11441880
TI  - Structures of the mind and universal music.

PMID- 11441881
TI  - Biologic responses to low doses of ionizing radiation: detriment versus hormesis.
      Part 1. Dose responses of cells and tissues.

PMID- 11441882
TI  - A stoic patient.

PMID- 11441883
TI  - Electric cautery lowers contamination threshold for infection by laparotomies.

PMID- 11441884
TI  - Saving external branch of superior laryngeal nerve during thyroidectomy.

PMID- 11441885
TI  - Cut-closed-reconnected Roux loop.

PMID- 11441886
TI  - The cut-closed-reconnected Roux loop.

PMID- 11441887
TI  - Kocher of the Kocher maneuver.

PMID- 11441888
TI  - The microsatellite instability phenotype in human colorectal carcinoma:
      relationship to sex, age, and tumor site.

PMID- 11441889
TI  - Possible mechanisms for ischemic colitis during alosetron therapy.

PMID- 11441890
TI  - Interleukin 10 and incidence of pancreatitis after therapeutic endoscopic
      retrograde cholangiopancreatography.

PMID- 11441891
TI  - IL-10 in post ERCP pancreatitis.

PMID- 11441892
TI  - Oral health for kids.

PMID- 11441894
TI  - Remove the censors!

PMID- 11441893
TI  - Professional flexibility.

PMID- 11441895
TI  - Oral healthcare in transition in Eastern Europe.
AB  - Big changes have occurred in the oral healthcare delivery systems of most Eastern
      European countries since the fall of the Berlin wall in 1989 and the demise of
      communism in the former USSR in 1991. In the new situation it was necessary to
      reform the political and social systems including healthcare. Reforms were
      started to improve the economy and, in comparison with Western Europe, the
      generally lower living standards. It is difficult to obtain comprehensive data on
      oral healthcare in Eastern European countries but this paper reports data from
      nine countries and provides a 'macro' view of the current situation in these
      countries. Many countries seem to have adopted a Bismarckian model for the
      provision of oral healthcare based on a sickness insurance system.

PMID- 11441896
TI  - Continuing professional development. Setting objectives for the organisation.

PMID- 11441897
TI  - Ingested foreign bodies associated with orthodontic treatment: report of three
      cases and review of ingestion/aspiration incident management.
AB  - Foreign body ingestion/aspiration episodes are potential complications in all
      branches of dentistry. The handling of small orthodontic components requires
      particular care, especially where the patient is supine or semi-recumbent. Three
      cases of foreign body ingestion are presented, involving patients undergoing
      orthodontic treatment. Once the foreign bodies had been located, all instances
      were treated using a combination of serial radiography and 'watchful waiting'.
      All patients remained asymptomatic during this period, although none of the
      foreign bodies were retrieved. No active intervention was deemed necessary, and
      the patients were able to resume their orthodontic treatment. The potential
      complications of ingestion/aspiration episodes are discussed and a management
      regime suggested.

PMID- 11441898
TI  - 'What do our patients really want from us?': Investigating patients perceptions
      of the validity of the Chartermark criteria.
AB  - BACKGROUND: The 'restructuring' of the NHS over the last decade has demanded a
      'market oriented' service more receptive to the needs and priorities of
      'clients'receiving health care. These changes have been important to the
      provision of dental health care in which there has been a similar need to provide
      increasingly patient and market oriented services. One of the ways in which
      quality care has been assessed within NHS Trusts is through the national
      'Chartermark' award, which identifies national centres of excellence in health
      care and research. AIM: The aim of this paper is to assess whether patients
      themselves considered the criteria identified by the Chartermark award important
      in the provision of good quality dental services METHOD: This is a pilot study
      consisting of a structured questionnaire conducted face-to-face with a
      'convenience' sample of 46 patients. ANALYSIS: Data were inputted into SPSS and
      thematic analysis was conducted on the data. RESULTS: The Chartermark criteria
      relevant to patient involvement were divided into four main themes.The findings
      from this small pilot study suggest that in relation to dental care, although
      patients are interested in information on standards, performance and complaints,
      there is considerable disinterest in organisational and financial dimensions.

PMID- 11441899
TI  - Factors predictive of difficulty of mandibular third molar surgery.
AB  - AIM: Historically the difficulty of third molar surgery has been judged using
      radiologically assessed dental factors specifically tooth morphology and
      position. This study investigated additional factors that have a bearing on the
      difficulty of extraction. STUDY DESIGN: A prospective study undertaken by three
      clinical assistant grade surgeons who removed 354 single mandibular third molar
      teeth under day case anaesthesia over the 4-year period (1994-1998). METHOD: Data
      relating to patient, dental and surgical variables were collected
      contemporaneously as the patients were treated. The difficulty of extraction was
      estimated by the surgeons pre-operatively using dental radiographic features and
      compared by the same surgeon within the actual surgical difficulty encountered at
      surgery. Operation time strongly related to both pre and post treatment
      assessments of difficulty and proved to be the best measure of surgical
      difficulty. RESULTS: Univariate analysis identified increased patient age, ethnic
      background, male gender, increased weight, bone impaction, horizontal angulation,
      depth of application, unfavourable root formation, proximity to inferior alveolar
      canal and surgeon as factors increasing operative time. Multivariate analysis
      showed that increasing age (P = 0.014), patient weight (P = 0.024), ethnicity (P
      = 0.019), application depth (P = 0.001), bone impaction (p=0.008) and
      unfavourable root formation (P = 0.009) were independent predictors for
      difficulty of extraction. CONCLUSIONS: Half of the six independent factors that
      predicted surgical difficulty of third molar extraction were patient variables.

PMID- 11441900
TI  - The role of acupuncture in controlling the gagging reflex using a review of ten
      cases.
AB  - The gagging reflex is a physiological reaction which safeguards the airway from
      foreign bodies. In some people this response is exaggerated to the extent that
      the acceptance/provision of dental treatment is not possible. The aim of this
      paper is to review the role of acupuncture in controlling gagging as a safe,
      cheap, quick and relatively non-invasive technique. METHOD: Ten people agreed to
      try ear acupuncture to control gagging during dental treatment. Prior to
      treatment the severity of gagging was assessed. Acupuncture needles were inserted
      into a specific anti-gagging point on each ear, manipulated briefly and left in
      situ. Dental treatment was then carried out and the effectiveness of the
      acupuncture in preventing gagging was assessed. After treatment, the needles were
      removed and the patient discharged. All acupuncture was carried out by a dentist
      trained in its use. RESULTS: Four people had a severe gag reflex which made
      treatment impossible and six had a very severe reflex which made treatment
      impossible and affected their dental attendance. Ear acupuncture completely
      controlled the gag reflex in eight cases (23 treatment episodes) and partially
      controlled the reflex in two cases (two treatment episodes). Dental treatment
      could be carried out in all cases and at all visits. The cost of materials was
      0.2 pounds per person per visit. Additional clinical time was in the order of 2-3
      minutes. There were no adverse reactions to the technique and, on all occasions,
      patients were fit to leave the surgery and travel home unaccompanied.
      CONCLUSIONS: Ear acupuncture was successful in controlling the gag reflex. It is
      a safe, quick, inexpensive and relatively noninvasive technique. A controlled
      clinical trial is required to investigate any placebo effect.

PMID- 11441901
TI  - Student operator-assistant pairs: an update.
AB  - OBJECTIVE: To seek the opinions of undergraduates using the operator-assistant
      pairs system. DESIGN: A five-year evaluation of third-, fourth- and fifth-year
      students using a short, anonymous questionnaire OUTCOME MEASURES: This study set
      out to evaluate, but does not attempt to formally assess, the system. RESULT:
      Most students enjoyed working in pairs, citing mutual support and collaborative
      learning as being the main advantages. However, 67% of responding third- year
      students, 79% of fourth-year students and 54% of fifth-year students indicated
      that they did not know why paired working had been introduced. CONCLUSIONS: The
      majority of students found the pairs system advantageous over teacher-led
      situations. It encouraged greater efficiency, mutual support and help and
      collaborative learning.

PMID- 11441902
TI  - Carvedilol in heart mitochondria: protonophore or opener of the mitochondrial
      K(ATP) channels?
AB  - Carvedilol ([1-[carbazolyl-(4)-oxy]-3-[2-methoxyphenoxyethyl) amino]-propanol
      (2)]) has been shown to protect cardiac mitochondria from oxidative stress. In
      this work we examined the mechanisms responsible for an observed depressive
      effect in the mitochondrial transmembrane potential (delta psi). Two possible
      mechanisms were considered: a protonophoretic activity and the opening of
      mitochondrial ATP-sensitive potassium channels. We show that carvedilol increases
      mitochondrial inner membrane permeability to protons, but not to potassium,
      causing an increase in state IV respiration in the presence and absence of
      oligomycin. By contrast, a K(ATP)-channel inhibitor, 5-hydroxydecanoic acid, did
      not affect carvedilol-induced depolarizations. Hence, our results suggest that
      carvedilol depresses mitochondrial delta psi by a weak protonophoretic mechanism.

PMID- 11441903
TI  - Circulating human corticotropin-releasing factor-binding protein levels following
      cortisol infusions.
AB  - Corticotropin-releasing factor-binding protein (CRF-BP) is a 37 kDa protein
      present in the brain and plasma and is known to regulate the actions of CRF. It
      has been demonstrated that CRF-BP in the brain and the pituitary appears to be
      positively regulated by glucocorticoids. In this study, the effect of various
      doses of hydrocortisone infusions on plasma CRF-BP levels was assessed. Four
      groups of 10 age-matched males received a 100 min infusion of either placebo
      (saline), 40 microg/kg/h, 300 microg/kg/h or 600 microg/kg/h hydrocortisone. CRF
      BP levels were measured via a LIRMA. In addition, levels of plasma ACTH and
      cortisol were measured by standard radioimmunoassay. As expected, plasma cortisol
      levels increased and plasma ACTH levels were suppressed following the infusion.
      When expressed as proportion of pre-infusion baseine, no significant changes in
      plasma CRF-BP levels were observed following the infusion for all hydrocortisone
      groups relative to the control group. However, a significant time-averaged
      positive correlation was found between CRF-BP and cortisol levels at low to
      moderate, but not high, cortisol levels. The data obtained in this study indicate
      that CRF binding protein levels within the time course examined may slightly
      appear to be affected in the peripheral circulation in response to pronounced,
      sustained hypercortisolemia.

PMID- 11441904
TI  - Pharmacological identification of the major subtypes of adrenoceptors involved in
      the canine external carotid vasoconstrictor effects of adrenaline and
      noradrenaline.
AB  - This study investigated the potential effects of adrenaline and noradrenaline on
      the external carotid blood flow of vagosympathectomised dogs and the receptor
      mechanisms involved. One minute (1 min) intracarotid infusions of adrenaline and
      noradrenaline produced dose-dependent decreases in external carotid blood flow
      without changes in blood pressure or heart rate. These responses, which remained
      unaffected after saline, were: (i) mimicked by the adrenoceptor agonists,
      phenylephrine (alpha1) and BHT933 (6-Ethyl-5,6,7,8-tetrahydro-4H-oxazolo [4,5-d]
      azepin-2-amine dihydrochloride; alpha2); (ii) abolished after phentolamine (2000
      microg/kg) unmasking a vasodilator component (subsequently blocked by
      propranolol; 1000 microg/kg); and (iii) partly blocked by rauwolscine (30 and 100
      microg/kg), and subsequently abolished by prazosin (100 microg/kg). Accordingly,
      rauwolscine (100 and 300 microg/kg) markedly blocked the responses to BHT933
      without affecting those to phenylephrine; likewise, prazosin (100 microg/kg)
      markedly blocked the responses to phenylephrine without affecting those to
      BHT933. These results show that both alpha1- and alpha2-adrenoceptors mediate
      vasoconstriction within the canine external carotid circulation. Moreover, after
      blockade of alpha1/alpha2-adrenoceptors, both adrenaline and noradrenaline
      exhibit a beta-adrenoceptor-mediated vasodilator component.

PMID- 11441905
TI  - Immobilization stress-induced thymocyte apoptosis in rats.
AB  - Immobilization of rats is a well known model of emotional stress. We studied
      apoptosis in rat thymocytes during immobilization for 2-8 hours (h). Terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)
      positive cells increased with time of immobilization. The positive cells
      increased significantly after 2 h and comprised about 33% of total cells after 8
      h. The apoptotic cells aggregated as scattered foci predominantly in the cortex
      of the thymus and diffusely distributed with time of the stress. The DNA
      laddering also increased with time of immobilization, which was inhibited by a
      glucocorticoid receptor antagonist, RU-486. These results suggest that the
      emotional stress evoked by immobilization induces thymocyte apoptosis through
      glucocorticoid overflow.

PMID- 11441906
TI  - Central and peripheral catecholamines regulate the exercise-induced elevation of
      plasma interleukin 6 in rats.
AB  - Several recent reports indicate that exercise elevates the plasma interleukin 6
      levels; however, the precise regulation of such an elevation still remains to be
      clarified. In this study, in order to clarify the requirements of central and
      peripheral catecholaminergic system for this exercise-induced interleukin 6
      elevation, rats were either intraperitoneally or intracerebroventricularly
      injected with 6-hydroxydopamine which depletes the catecholamine in the central
      or peripheral tissues. As a result, our exercise protocol elevated the plasma
      interleukin 6, ACTH, and corticosterone levels in response to exercise. All such
      exercise-induced increases in the interleukin 6, ACTH, and corticosterone levels
      were significantly inhibited by pretreatment with an intracerebroventricular
      injection of 6-hydroxydopamine. In the intraperitoneal 6-hydroxydopamine-treated
      animals, the exercise-induced interleukin 6 elevation was significantly
      suppressed compared with the vehicle-treated animals, although no significant
      difference was found in either the ACTH level or the corticosterone level between
      both groups of animals. These results thus suggest that central and peripheral
      catecholamines are involved in the regulation of the exercise-induced interleukin
      6 elevation.

PMID- 11441907
TI  - Human urotensin II increases coronary perfusion pressure in the isolated rat
      heart: potentiation by nitric oxide synthase and cyclooxygenase inhibition.
AB  - Urotensin II (U-II) is a cyclic peptide, recently cloned in man and present in
      cardiac tissue and arteries. The effects of human U-II (hU-II) on coronary
      perfusion pressure (CPP) were investigated in isolated rat hearts perfused
      retrogradely via the aorta at constant flow. hU-II produced a concentration
      dependent increase in CPP (pEC50 8.6 +/- 0.3, n = 8), the maximum increase in CPP
      (12 +/- 4 mmHg) was obtained at 10(-7) M hU-II. At higher concentrations of hU-II
      CPP fell back towards baseline. Endothelin-1 produced a maximum increase in CPP
      of 63 +/- 11 mmHg within the concentration-range studied. Addition of the NO
      synthase inhibitor L N(G)nitro-arginine methyl ester (10(-4) M) and the
      cyclooxygenase inhibitor, indomethacin (10(-5) M) to the perfusion solution had
      no effect on the pEC50 value for hU-II, but significantly increased the maximum
      constriction (to 34 +/- 7 mmHg, n = 8, p < 0.05) and inhibited the later dilator
      response to hU-II. These results suggest that receptors for hU-II are present in
      the coronary vasculature and that smooth muscle contraction is modulated by the
      release of dilator factors, including NO and prostacyclin. Endothelial function
      is therefore likely to be of primary importance in modulating the coronary
      vasoconstrictor effects of hU-II in vivo.

PMID- 11441908
TI  - Effect of St. John's wort on free radical production.
AB  - St. John's wort (Hypericum perforatum) is an herbal compound used in the
      treatment of burns, bruises, swelling, anxiety, and most recently, mild to
      moderate depression. The present study was designed to evaluate the antioxidant
      properties of St. John's wort in both cell-free and human vascular tissue. The
      experiment was performed initially in a cell-free system using Krebs buffer and a
      combination of xanthine/xanthine oxidase to initiate the production of the
      superoxide radical. Additionally, human placental vein was incubated in Krebs
      buffer without xanthine or xanthine oxidase to study the effects of St. John's
      wort on human tissue in vitro. Commercially available formulations of St. John's
      wort, standardized to either hypericin or hyperforin, were dissolved in an
      alkaline solution, and the following dilutions were made: 1:1, 1:2.5, 1:5, 1:7.5,
      1:10, and 1:20. Lucigenin chemiluminescence was used to measure free radical
      production in both systems. A pro-oxidant effect was seen at the highest
      concentration, 1:1. Lower concentrations revealed antioxidant properties of the
      compound. All dilutions below 1:1 in both systems showed a dose-related inverse
      relationship of superoxide inhibition. The largest suppression was seen at the
      most dilute concentration, 1:20. The addition of 10(-3) M tiron inhibited the
      chemiluminescence signal, thereby confirming the production of superoxide. The
      results of this study suggest that St. John's wort inhibits free radical
      production in both cell-free and human vascular tissue.

PMID- 11441909
TI  - Effect of cyclosporine, a P-glycoprotein inhibitor, on the pharmacokinetics of
      cefepime in rat blood and brain: a microdialysis study.
AB  - In clinical application, cefepime and cyclosporine are regularly combined in the
      treatment of organ transplant patients, so the interaction of these two drugs can
      be hypothesized. Therefore, the pharmacokinetics of cefepime alone and in
      combination with cyclosporine in rat using microdialysis coupled with HPLC-UV on
      line system was evaluated in the study. Cefepime at three doses (20, 50, and 100
      mg/kg) showed linear kinetics. After addition of cyclosporine, the mean residence
      time was increased from 34.9 min to 48.6 min (p<0.05, n=6), and the area under
      the concentration versus time curve (AUC) increased from 4775 min microg/ml to
      6960 min microg/ml (p<0.01, n=6). While in the brain, AUC increased from 64.3 min
      microg/ml to 110.2 min microg/ml. In summary, cyclosporine (20 mg/kg) could
      significantly alter the simultaneously administered cefepime (50 mg/kg) unbound
      drug pharmacokinetic parameters in both blood and brain.

PMID- 11441910
TI  - Transcriptional regulation of galectin-10 (eosinophil Charcot-Leyden crystal
      protein): a GC box (-44 to -50) controls butyric acid induction of gene
      expression.
AB  - Galectin-10 (gal-10, also known as Charcot-Leyden crystal protein) is a member of
      the galectin family of beta-galactoside binding proteins that is expressed
      uniquely in eosinophilic and basophilic leukocytes. To gain a better
      understanding of galectin gene expression, we present an analysis of the
      transcriptional regulation of the gene encoding gal-10. Analysis of the minimal
      promoter revealed nine consensus-binding sites for transcription factors,
      including several that are also found in the minimal promoters of galectins -1, 
      2, and -3. The decrease in gal-10 promoter activity after disruption of either
      the GC box (-44 to -50) or the Oct site (-255 to -261) suggests that these sites,
      along with the previously characterized GATA and EoTF sites, are necessary for
      full promoter activity. By supershift analysis, we demonstrate binding of the
      transcription factors Sp1 and Oct1 to the consensus GC box and the Oct site,
      respectively. Similar to gal-1, gal-10 expression is induced by butyric acid, an
      effect that is lost upon ablation of the GC box. Additionally, we demonstrate
      AML3 binding to the consensus AML site and YY1 binding to the Inr sequence, both
      elements functioning as silencers in the gal-10 promoter.

PMID- 11441911
TI  - Non-invasive echocardiographic studies in mice: influence of anesthetic regimen.
AB  - Transgenic murine models of cardiovascular disease offer great potential insights
      regarding mechanisms of human disease, but efficient and reliable methods for
      phenotype evaluation are necessary. We employed non-invasive echocardiography to
      evaluate hemodynamic parameters in mice, and evaluated statistical reliability of
      these parameters with respect to anesthesia regimen. Male CF-1 mice received
      inhaled halothane (0.25-0.75% in 95% O2) or ketamine/xylazine (80/10 mg/kg i.p.)
      and 2-dimensional, M-mode, and Doppler ultrasound imaging were used to assess
      cardiac contractility and aortic flow velocities. Halothane was more convenient
      and reliable with respect to rate of induction, reversal, and control of
      anesthetic depth. At comparable levels of anesthesia, ketamine/xylazine produced
      significant reductions in heart rate (308 +/- 14 vs. 501 +/- 14 bpm, p<0.001),
      left ventricular fractional shortening (41.7 +/- 1.3 vs. 49.3 +/- 1.0%, p<0.001),
      and cardiac output (7.6 +/- 0.5 vs. 11.5 +/- 0.6 ml/min, p<0.001) when compared
      to halothane inhalation. No change in stroke volume or peak aortic velocity was
      observed. Correlation analyses revealed highly significant positive relationships
      between heart rate and fractional shortening (r=0.61, p<0.002) and cardiac output
      (r=0.88, p<0.001) but no relation to stroke volume or aortic velocity.
      Variability of intra-animal and intragroup parameter estimation were frequently 2
      fold larger for ketamine/xylazine anesthesia vs. halothane. Statistical power
      analysis showed the increased measurement error for ketamine/xylazine leads to
      much larger numbers of mice/group to achieve identical statistical sensitivity.
      These data further illustrate the feasibility of echocardiography for rapid, non
      invasive cardiovascular assessment in mice. However, several obtainable
      parameters are highly sensitive to both heart rate and anesthetic used and the
      choice and control of anesthetic are critical for physiologically relevant
      performance parameters and maximal ability to detect statistical differences
      among groups. Thus, for these non-invasive studies, inhalation anesthesia with
      agents such as halothane is superior to anesthesia induced by ketamine/xylazine
      administration.

PMID- 11441912
TI  - Increased oxidative stress in childhood atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease of unknown
      etiology. To examine the involvement of impaired homeostasis of oxygen/nitrogen
      radicals in childhood AD, we compared the levels of urinary 8-hydroxy-2'
      deoxyguanosine (marker of oxidative stress), nitrite/nitrate (marker of nitric
      oxide synthesis) and selenium (marker of selenium store) in 27 children with AD
      to those of 25 healthy control children. Urinary 8-hydroxy-2'-deoxyguanosine was
      significantly higher and nitrite/nitrate levels were significantly lower in
      patients with AD than in the control. Urinary selenium levels were similar in
      both groups. Our findings suggest that impaired homeostasis of oxygen/nitrogen
      radicals and increased oxidative stress are involved in the pathophysiology of
      childhood AD, and indicate that suppression of oxidative stress might be a
      potentially useful strategy for the treatment of AD.

PMID- 11441913
TI  - Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from
      Paecilomyces tenuipes.
AB  - Paecilomyces tenuipes is one of the famous Chinese medicinal entomopathogenic
      fungi that parasites in the lavae of silkworm. Two cytotoxic components were
      isolated from methanolic extract of the carpophores of this fungus that was
      cultivated artificially. Spectral analyses of the cytotoxic components showed
      that they were known ergosterol peroxide (5alpha,8alpha-epidioxy-24(R)
      methylcholesta-6,22-dien-3beta-ol) and acetoxyscirpenediol (4beta-acetoxyscirpene
      3alpha,15-diol) that were isolated for the first time from this fungus. The 50%
      inhibitory concentrations (IC50) of ergosterol peroxide against human gastric
      tumor cell line (SNU-1), human hepatoma cell line (SNU-354), human colorectal
      tumor cell line (SNU-C4) and murine sarcoma-180 were 18.7, 158.2, 84.6 and 74.1
      microM, respectively. The IC50 values of acetoxyscirpenediol against SNU-1, SNU
      C4, SNU-354 and sarcoma-180 were 1.2,4.0, 2.2 and 1.9 microM, respectively.
      Cytotoxic activities of acetoxyscirpenediol were about 4.0-6.6 times stronger
      than those of cisplatin which is currently used clinically for cancer patients.

PMID- 11441914
TI  - Secretion of proadrenomedullin N-terminal 20 peptide from cultured neonatal rat
      cardiac cells.
AB  - Proadrenomedullin N-terminal 20 peptide (PAMP) is generated from post
      transcriptional enzymatic processing of a 185-amino acid precursor for
      adrenomedullin (AM), a potent vasodilator peptide. We have reported that AM is
      secreted from cultured neonatal rat cardiac myocytes and fibroblasts, and that
      secreted AM modulates the growth of these cells; however, it is unknown whether
      or not the cardiac cells produce PAMP. In this study, we examined the production
      of PAMP in cultured neonatal rat cardiac myocytes and fibroblasts. Both the
      cardiac myocytes and fibroblasts cultured with serum-free media secreted PAMP
      time-dependently at rates of 5.7+/-0.9 fmol/10(5) cells/40 h and 8.4+/-0.7
      fmol/5x10(4) cells/48 h (mean+/-SD), respectively. Reverse-phase high performance
      liquid chromatography showed that immunoreactive PAMP secreted from these cells
      was identical to PAMP[1-20], a whole active molecule. PAMP and AM secretions were
      significantly (P<0.01) stimulated by 10(-6) mol/L angiotensin II (Ang II) and 10%
      fetal bovine serum (FBS) in myocytes and fibroblasts, whereas the ratio of PAMP
      to AM secretion in the myocytes was smaller than that of the fibroblasts. These
      results suggest that PAMP is secreted along with AM from rat cardiac myocytes and
      fibroblasts, and the secretion is augmented by the growth-promoting stimuli of
      Ang II and FBS for these cells.

PMID- 11441915
TI  - Effect of cadmium on gap junctional intercellular communication in primary
      cultures of rat renal proximal tubular cells.
AB  - Cadmium mainly accumulates in the kidney and causes renal injury. To clarify the
      mechanism of Cd nephrotoxicity, we investigated the effects of this element on
      intercellular communication through gap junction channels in primary cultures of
      rat renal proximal tubular cells. Sixty minutes after exposure to 100 microM Cd,
      dye coupling experiments showed that gap junctional intercellular communication
      (GJIC) was significantly inhibited. This inhibition occurred before the
      appearance of cytotoxicity. Intracellular calcium concentrations [Ca2+]i, which
      modulate the function of gap junctions, gradually increased after exposure to Cd
      and reached a maximum after 60 minutes. These results suggest that the inhibition
      of GJIC as a result of Cd exposure is related to an increase in [Ca2+]i, and that
      GJIC inhibition may be an indicator of nephrotoxicity.

PMID- 11441916
TI  - Short-term hyperglycemia induces lymphopenia and lymphocyte subset
      redistribution.
AB  - Alterations in lymphocytes are a common finding in both type I and type II
      diabetes. Autoimmune phenomena in type I diabetes, the stage of the diabetic
      disorder and metabolic effects of therapeutic interventions may also affect
      actual distribution of lymphocyte phenotypes. This study investigated
      immunological effects specific to standardized hyperglycemia in non-diabetic
      individuals to exclude immunological changes potentially related to diabetes
      stage and treatment. 37 subjects (mean age +/- SD 39 +/- 5 years) underwent a
      sequence-controlled crossover with oral administration of a solution containing
      either 75 g glucose or artificial sweetener (i.e. placebo). At rest and at two
      hours, counts of white blood cells (WBC), mixed lymphocytes, mature T-cells
      (CD3), T-helper cells (CD4), T-suppressor/ cytotoxic cells (CD8), B-cells (CD19),
      natural killer cells (CD16/CD56), and interleukin-2 receptor bearing peripheral
      blood mononuclear cells (CD25) were measured by flow cytometry. Subjects showed a
      significant decrease in WBC, lymphocytes, and all lymphocyte subsets with the
      OGTT compared with the placebo solution (p < .05 to p < .001). In non-diabetic
      individuals, short-term hyperglycemia induces immunological changes that may be
      relevant to explain similar findings in patients with diabetes mellitus. Future
      studies need to validate these findings and their potential clinical implications
      in a diabetic population.

PMID- 11441917
TI  - Brain t-complex polypeptide 1 (TCP- 1) related to its natural substrate beta1
      tubulin is decreased in Alzheimer's disease.
AB  - The t-complex polypeptide 1 is a selective molecular chaperone in tubulin
      biogenesis, by that nascent tubulin subunits are bound to t-complex polypeptide 1
      and released in assembly competent forms. In neurodegenerative diseases with
      Alzheimer pathology cytoskeletal proteins are deficient and aggregated. Therefore
      we examined t-complex polypeptide 1 as represented by the zeta subunit and its
      specific substrate beta 1 tubulin represented by a truncated product in six brain
      regions of nine patients with Alzheimer's disease, nine patients with Down
      syndrome and nine controls. We used 2 dimensional electrophoresis with in-gel
      digestion and matrix-assisted laser desorption/ ionization- mass spectrometry for
      the separation and identification of human brain t-complex polypeptide 1 and beta
      1 tubulin. When t-complex polypeptide I was related to its natural and specific
      substrate beta 1 tubulin, the ratio was significantly decreased in the temporal,
      frontal, parietal cortex and in thalamus of patients with Alzheimer's disease. In
      Down syndrome the t-complex polypeptide 1/beta 1 tubulin ratio was significantly
      increased in frontal and parietal cortex suggesting a different mechanism for
      aggregation of microfilament proteins e.g. beta 1 tubulin. Relatively decreased
      molecular chaperoning of beta 1 tubulin by t-complex polypeptide 1 may lead to
      misfolded tubulin aggregating and accumulating in plaques and tangles, a hallmark
      of Alzheimer's disease. Our contribution provides first clues for a mechanism of
      microtubular accumulation in Alzheimer's disease and challenges further studies
      on different chaperones and chaperonins in the brain of patients with
      neurodegenerative diseases.

PMID- 11441918
TI  - Impaired repair activity of a truncated DNA polymerase beta protein.
AB  - DNA polymerase beta (polbeta) is an essential enzyme for gap filling synthesis in
      damaged DNA template involved in base excision repair pathway. A truncated
      polbeta protein is expressed in primary colorectal and breast adenocarcinomas. To
      determine a possible alteration in the functions of the enzyme, a human cell line
      named HeLapolbetadelta expressing the truncated form of polbeta has been
      established. These cells revealed a significantly reduced level of repair
      activity evaluated by gap filling synthesis and polbeta activity. More
      importantly, the HeLapolbetadelta cells are hypersensitive to MNNG, a DNA
      alkylating agent. It appears from the responses that the gap filling synthesis of
      WT cells, a HeLa cell line overexpressing wild-type polbeta protein, was
      inhibited by HeLapolbetadelta protein.

PMID- 11441919
TI  - Dexamethasone increases inhibin and estradiol secretion mediated by endogenous
      FSH in equine chorionic gonadotropin (eCG)-primed immature female rats.
AB  - In the present study, we have examined whether the effects of dexamethasone on
      follicle stimulating hormone (FSH) secretion were mediated by hypophysiotropic
      factors, and whether the increased levels of FSH induced by dexamethasone can
      stimulate ovarian functions in equine chorionic gonadotropin (eCG)-primed
      immature female rats. Dexamethasone (500 microg) significantly increased serum
      concentrations of FSH in hypophysectomized rats implanted with pituitary under
      the kidney capsule, as well as in intact rats. Serum concentrations of inhibin
      and estradiol in eCG (2.5, 5 i.u.)-primed rats were significantly increased by
      simultaneous treatment with dexamethasone (500 microg) and eCG. These
      simultaneous effects were not confirmed in hypophysectomized rats. The results
      had shown that hypophysiotropic factors do not mediate the selective increase of
      FSH secretion caused by dexamethasone. Dexamethasone induces the excess amount of
      FSH secretion from anterior pituitary and this FSH can stimulate inhibin and
      estradiol secretion in eCG-primed immature female rat.

PMID- 11441920
TI  - Protective effect of XY99-5038 on hydrogen peroxide induced cell death in
      cultured retinal neurons.
AB  - XY99-5038 is a preparation from a specific formula provided by Dr. Yan Xin, a
      renowned Traditional Chinese Medicine specialist. This formulation has proven to
      be effective without side effects but has not been studied under rigorous
      laboratory conditions. In order to investigate the role of XY99-5038 in
      protecting neurons from degeneration, we used retinal neuronal culture as a model
      system to study the protective effects of XY99-5038 against hydrogen peroxide
      (H2O2) induced cytotoxicity. Basic fibroblast growth factor (bFGF), a potent
      neurotrophic factor, was employed as comparable agent. Retinas of 0-2 days old
      Sprague-Dawley rats were isolated, dissociated, and the neurons maintained for 2
      weeks in a synthetic serum-free media. Cytotoxicity was determined by MTT (3,(4,5
      dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide) and LDH (Lactate
      dehydrogenase) assays, whereas apoptotic cell death was evaluated by the TUNEL
      (TdT-mediated digoxigenin-dUTP nick-end labeling) assay. Treatment with H2O2
      significantly induced death of retinal neurons. Pretreatment with XY99-5038 prior
      to insult greatly inhibited or attenuated H2O2 induced cytotoxicity and
      apoptosis. These effects were shown to be dose-dependent. Our data also show that
      the protective effect of XY99-5038 is more potent than that of bFGF. Our data
      suggest that XY99-5038 could be a potential agent in the treatment of disorders
      associated with oxidative damage.

PMID- 11441921
TI  - Sustained norepinephrine stimulation induces different regulation of expression
      in three alpha1-adrenoceptor subtypes.
AB  - The norepinephrine (NE)-induced regulation of alpha1-adrenoceptors (ARs)
      expression in human embryonic kidney (HEK) 293 cells stably expressing cloned
      alpha1-AR subtypes with similar receptor densities was investigated. In the
      presence of 10 microM propranolol, the treatment of cells with 10 microM NE for 4
      72 h down-regulated alpha1A- and alpha1D-AR. but increased alpha1B-AR expression
      in a time-dependent manner. The down-regulation of alpha1A-AR reached maximum of
      40.3 +/- 14.7 % at 48h. The down-regulation of alpha1D-AR reached maximum of 51.3
      +/- 3.7% at 24h. With the stimulation of NE, alpha1B-AR density was increased
      maximally by 112.4 +/- 43.4% at 48h. The protein kinase C (PKC) inhibitor
      calphostin C or R0-31-8220 abolished the NE-induced down-regulation of alpha1A-
      and alpha1D-AR, but showed no effect on the up-regulation of alpha1B-AR. The PKC
      agonist PMA not only mimicked the NE-induced down-regulation of alpha1A- and
      alpha1D-AR, but also induced a down-regulation of alpha1B-AR. The endoplasmic
      reticulum Ca2+-ATPase inhibitor cyclopiazonic acid (CPA) or thapsigargin, or the
      calcium chelator BAPTA/AM did not affect the down-regulation of alpha1A-AR, but
      inhibited the up-regulation of alpha1B-AR induced by NE. Calmodulin antagonist W
      7. tyrosine kinase inhibitor genistein or tyrphostin A25 had no effect on NE
      induced up-regulation of alpha1B-AR. The results suggest that three alpha1-AR
      subtypes are differently regulated by sustained NE stimulation with different
      signal transduction pathways.

PMID- 11441922
TI  - Protection of salvia miltiorrhiza against aflatoxin-B1-induced
      hepatocarcinogenesis in Fischer 344 rats dual mechanisms involved.
AB  - Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese
      medicine for treating liver diseases. Recent experimental evidence indicates that
      it has anti-tumor potential. In this study, the effect of SM on alfatoxin B1
      (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats.
      AFB1 (40 microg/100 g body wt, by gavage) was administered once a week for 24
      weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week
      by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during
      AFB1 exposure. Results showed that the elevation of serum alanine
      aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was
      almost completely abolished by the treatment of SM, indicating that SM could
      prevent AFB1-induced liver cell injury. It was further observed that SM
      substantially reduced glutathione S-transferase placenta form (GST-P) positive
      foci formation and GST-P mRNA expression caused by AFB1, which clearly suggests
      that SM is effective in preventing AFB1-induced hepatocarcinogenesis.
      Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a
      corresponding decrease in AFB1-DNA adducts formation as well as AFB1-induced
      oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also
      indicate that the protective effect of SM might be mediated through dual
      mechanisms: (i) the enhancement of AFB1 detoxification pathway, especially the
      induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.

PMID- 11441923
TI  - A novel lectin from Pseudostellaria heterophylla roots with sequence simularity
      to Kunitz-type soybean trypsin inhibitor.
AB  - From the roots of the Chinese medicinal herb Pseudostellaria heterophylla a
      single-chained lectin with a molecular weight of 36 kDa and high hemagglutinating
      activity was isolated. The lectin was adsorbed on DEAE-cellulose in 10 mM Tris
      HCI buffer (pH 7.4) and was eluted by the same buffer containing 50 mM NaCl. It
      was adsorbed on SP-Sepharose in 10mM NH4OAc (pH 4.5) and eluted by approximately
      0.5 M NaCl in the same buffer. The hemagglutinating activity of the lectin could
      not be inhibited by a large variety of monosaccharides, but was largely abrogated
      by exposure to 0.05 M HCl, 0.05M NaOH or 80 degrees C. However, about 50% of the
      activity remained after exposure to 0.025M NaOH or 40 degrees C. Despite
      possession of an N-terminal sequence exhibiting some similarity to thaumatin-like
      proteins with antifungal activity, the lectin was devoid of antifungal activity.
      The lectin exerted some inhibitory effect on the glycohydrolases alpha
      glucosidase, beta-glucosidase and beta-glucuronidase which are involved in HIV
      infection but had no suppressive action on human immunodeficiency virus-type 1
      reverse transcriptase.

PMID- 11441924
TI  - Pharmacokinetics of intrathecal transferrin-ricin a chain immunotoxin.
AB  - We have studied the pharmacokinetics of an anti-transferrin receptor immunotoxin
      following intrathecal (i.t.) and intravenous (i.v.) bolus inoculation in healthy
      rats. After i.t. inoculation of 4.9 microg transferrin-ricin A-chain (Tfn-RTA) we
      have measured the immunotoxin concentration in the cerebrospinal fluid (CSF), in
      the brain tissue and in the peripheral blood. After i.v. administration of 4.9
      microg Tfn-RTA the concentration of Tfn-RTA immunotoxin was evaluated in the
      peripheral blood. We found that the clearance of Tfn-RTA from the CSF is rapid
      (9.1 microLmin(-1)), the immunotoxin then diffuses into the brain tissue and in
      the peripheral blood where it reaches concentrations below the MTC50 (Minimum
      Toxin Concentration 50%). The rate of immunotoxin elimination from the peripheral
      blood following either i.v. or i.t. administration are similar (kel = 0.0021 min(
      1) vs. 0.0025 min(-1)). Thus, in the healthy rat the immunotoxin does not
      accumulate following i.t. inoculation, reaching non toxic concentrations in the
      brain tissue and in the peripheral blood, whereas in the CSF as well as at the
      interface CSF/brain tissue the immunotoxin may reach potentially therapeutic
      concentrations. In conclusion we believe that the i.t. inoculation of an
      immunotoxin could be considered a potentially useful route of administration in
      the treatment of leptomeningeal carcinomatosis.

PMID- 11441925
TI  - Heroin-induced changes of catecholamine-containing particles in male rat
      cerebellar cortex.
AB  - The content and distribution of catecholamine-containing formations in the
      cerebellum of untreated and heroin-treated male rats, was visualized by glyoxylic
      acid-induced histofluorescence, in an attempt to define the adaptive mechanisms
      leading to heroin dependent tolerance as well as identify a biological role for
      these formations. Repeated heroin administration increased the number of
      specifically organized intracellular catecholamine containing particles,
      including grain (diameter less than 0.8 microm) and aggregate (diameter greater
      than 1 microm) forms, in all cerebellar cortical layers examined one hour after
      the last injection of the drug, relative to controls. The number of grains in all
      cerebellar cortical layers examined and aggregates in the granular layer,
      returned to normal or near normal baseline levels within twenty four hours after
      the last injection of the drug. The analogous baseline of the aggregates in the
      Purkinje cell layer primarily and the Molecular layer secondarily remained
      significantly elevated by 86% and 50% respectively, relative to controls.
      Catecholamine-heroin interactions most likely mediated this elevation that was
      related directly to the heroin-dependent state of tolerance. These findings
      indicate that heroin administration to heroin-tolerant rats leads to the
      formation of unusually large intracellular aggregates with catecholamines in the
      Purkinje cells of the cerebellum primarily and support a direct role for these
      formations in the modulation of biogenic amine bioavailability. We conclude that
      adaptation to drug exposure involves multiple homeostatic interactions, with
      sympathetic activation at the level of catecholamine reorganization and
      redistribution playing a major role in rat cerebellar cortex.

PMID- 11441926
TI  - Induction of C-reactive protein, serum amyloid P component, and kininogens in the
      submandibular and lacrimal glands of rats with experimentally induced
      inflammation.
AB  - The mRNAs for acute-phase proteins and kininogens were found to be increased in
      the submandibular gland (SMG) and extraorbital and intraorbital lacrimal gland
      (ELG and ILG) in response to experimentally induced inflammation in rats; i.e.,
      24 hours after subcutaneous injection of turpentine oil, mRNAs for C-reactive
      protein (CRP), serum amyloid P component (SAP), and H- and T-kininogens were
      induced in the SMG, ELG, and ILG of rats, whereas these mRNAs were not detected
      in the same tissues of normal control rats. The induction of mRNAs for these
      inflammatory proteins by turpentine oil was preceded by a transient increase in
      the level of mRNA for tumor necrosis factor-alpha (TNF-alpha) at 6 hours after
      subcutaneous injection of the oil. This was confirmed by injection of another
      inflammation inducer, lipopolysaccharide (LPS), which induced the TNF-alpha mRNA
      in the same way at 6 hours as turpentine oil did. The up-regulation of acute
      phase proteins including kininogens in the SMG, ELG, and ILG suggest the
      existence of a strict defense system in the exocrine glands.

PMID- 11441927
TI  - The Swedish Council on Technology Assessment in Health Care (SBU) systematic
      overview of chemotherapy effects in some major tumour types--summary and
      conclusions.
AB  - This report by The Swedish Council on Technology Assessment in Health Care (SBU)
      reviews, classifies, and grades the scientific literature on cancer chemotherapy
      in some major tumour types, describes the practice of chemotherapy in Sweden,
      compares practice with scientific knowledge, and analyses the costs and cost
      effectiveness of chemotherapy. The report is intended primarily for decision
      makers at various levels, both practitioners and administrators. It is also of
      interest for the medical profession. The extensive body of scientific literature
      was reviewed according to strict criteria that reflected the scientific weight of
      the literature. Sixteen experts representing different disciplines (oncology,
      surgery, internal medicine, health economy and quality of life research)
      participated in the literature review. Each section was discussed within the
      project group and was reviewed by at least one, but usually two international
      researchers. Additional input was provided by national experts representing
      different scientific disciplines. For the final evaluation to be as close to the
      objective truth as possible, a concerted effort was made to guarantee objectivity
      and thorough assessment of current knowledge about the effects of chemotherapy on
      the selected cancers. The tumour types selected for this assessment include
      firstly those types where three investigations had shown an increased use of
      chemotherapy in Sweden during the latest decade. These were non-small cell lung
      cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary
      bladder cancer. Secondly, the two tumour types comprising the greatest number of
      patients treated with chemotherapy in Sweden, breast cancer and haematological
      malignancies, were included. Among the haematological malignancies, the most
      prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia
      (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the
      large B-cell type and indolent NHL of follicular type were evaluated. These
      constitute about 75%, of all haematological malignancies. Thirdly, ovarian cancer
      was included since chemotherapy has been extensively used and since, at the time
      of the planning of this overview, a group of very expensive drugs, the taxanes,
      had preliminarily shown promising results. A wealth of scientific literature has
      been published on cancer therapy. The review presented in this report is limited
      to scientific studies judged to be important for evaluating chemotherapy
      efficacy. Assessments of the content and quality of these studies, and a critical
      summary of the results in all stages of the selected tumours, have never before
      been attempted in this way. However, similar comprehensive overviews of certain
      stages of the tumours have previously been made. These overviews were also
      critically evaluated. Totally 1,496 studies involving 558,743 patients were
      reviewed. The survey of practice of chemotherapy use involved all departments of
      surgery, urology, gynaecology, internal medicine including haematologic units,
      pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two
      health care regions in Sweden, covering 39% of the Swedish population. During the
      4 weeks of the survey, all patients with the diagnoses concerned who received
      chemotherapy were registered. The study included 1,590 patients. The working
      group's general conclusions are summarised in the following points: The
      literature on the effects of chemotherapy is extensive. Chemotherapy has a well
      documented role in the curative and palliative treatment of patients with several
      types of cancer. The use of chemotherapy is of utmost importance for the
      possibility of cure in certain tumour types. In other tumours, chemotherapy
      increases the possibility of cure when added to local and regional treatments,
      particularly surgery. In the instances of no possibility of cure, chemotherapy
      may to a variable extent improve both patient survival and well-being. In Sweden
      chemotherapy is largely used in accordance with that documented in the scientific
      literature. The extent of both over- and under-treatment seems to be limited but
      cannot be excluded at the individual patient level. The literature-based
      knowledge is scientifically of lower quality in the most chemotherapy sensitive
      tumours than in tumours showing more limited sensitivity. In the more sensitive
      tumours, positive effects on a symptomatic stage and survival were seen several
      decades ago. In those days, clinical treatment studies did not fulfil the current
      high quality requirements. Small life-prolonging effects of chemotherapy are
      sometimes very well documented in large, high quality scientific studies. Some of
      these s

PMID- 11441928
TI  - The Swedish Council on Technology Assessment in Health Care (SBU) report on
      Cancer Chemotherapy--Project objectives, the working process, key definitions and
      general aspects on cancer trial methodology and interpretation.
AB  - The major objective of the Swedish Council on Technology Assessment in Health
      Care (SBU in its Swedish abbreviation) Chemotherapy Project was to review and
      assess the evidence, as presented in the scientific literature, for the use of
      chemotherapy in some major tumour types. The purpose of this assessment was to
      establish the current evidence-based role of this treatment modality in various
      settings in these tumour types. The basis for the assessment was the perspective
      of the conditions in Swedish health care and a prospective survey within the
      project detailed the use of chemotherapy in two health-care regions in Sweden.
      This formed the basis for an assessment of the use of chemotherapy in relation to
      scientific evidence. The project focused on standard cytotoxic chemotherapy,
      whether delivered at conventional doses or at higher doses with various
      supportive actions, and did not address the role of other emerging approaches
      that could broadly be included under the heading chemotherapy, e.g. drugs with
      anti-angiogenesis and anti-metastatic properties or chemopreventive drugs. In
      this introduction, the project objectives, working process, key definitions and
      general aspects on cancer trial methodology and interpretation are presented and
      discussed.

PMID- 11441929
TI  - What is cancer chemotherapy?
AB  - The importance of chemotherapy for cure of cancer is increasing, especially with
      its use as adjuvants to local therapy. Furthermore, in advanced disease, when the
      tumour has disseminated from its place of origin, chemotherapy has an expanding
      role in efforts to relieve cancer-related symptoms and to prolong life. Despite
      its shortcomings, chemotherapy, therefore, is an important treatment modality in
      oncology and will probably remain so for considerable time. This presentation,
      within the frame of The Swedish Council on Technology Assessment in Health Care
      (SBU) project to review cancer chemotherapy, aims to provide a brief overview of
      the field cancer chemotherapy. It includes a historical perspective of cancer
      chemotherapy, some practical aspects and theoretical considerations with respect
      to the action of, resistance to and metabolism of these drugs. Furthermore, some
      outlooks into the nearest future with respect to ways to improve and develop
      cancer chemotherapy are provided as well as some aspects of chemotherapy from an
      employee-protection perspective.

PMID- 11441930
TI  - Assessment of quality of life during chemotherapy.
AB  - Increasingly more aggressive chemotherapy together with expected small
      differences between treatments with respect to objective endpoints has heightened
      awareness about the importance of addressing how patients experience and value
      the impact that treatment has had on their overall life situation. Assessment of
      a patient's quality of life (QoL) is now conceptually viewed as an important
      complement to traditional objective evaluation measures. It was therefore
      considered important to review the basis for the assessment of this endpoint when
      The Swedish Council of Technology Assessment in Health Care (SBU) performed a
      systematic overview of chemotherapy effects in several tumour types. The group
      came to the following conclusions: QoL assessments, mostly by patient self
      reporting in questionnaires, have come increasingly into use during the past
      decade. A number of general, cancer-specific and cancer diagnosis-specific
      instruments have been developed. There is at present little need for development
      of new cancer instruments, although specific treatment modalities and tumour
      types may need new additional modules. A predefined hypothesis should determine
      the instrument to be used. Since the selection of a QoL instrument in a specific
      study influences both the results and the conclusions, it is essential to
      carefully select the instrument or instruments that have the greatest likelihood
      of identifying relevant differences between treatment alternatives.
      Interpretation of QoL data is more difficult than interpretation of objective
      endpoints such as survival time, objective response rates or toxicity. Despite
      these difficulties, QoL analyses have provided new insights into the advantages
      and disadvantages of various treatments not provided by traditional end-points.
      Some palliative treatments seemingly increase patients' QoL despite side-effects
      or the lack of, or marginal, increases in survival. When using potentially
      curative chemotherapy, it is not a matter of when the treatment should be
      started, but rather when it should be concluded. When using less active
      chemotherapy, the expected small therapeutic gains must be weighed against the
      QoL costs of using the therapy: does the toxicity and/or the inconvenience of the
      proposed treatment justify the expected gain? When it is found that the strain on
      the patient is greater than the effects of the cancer, treatment must be
      discontinued. It is not possible to determine whether or not the advantages of
      palliative chemotherapy are worth their costs without knowledge about patients'
      personal values regarding the influence on factors of relevance for QoL. The
      mostly used QoL questionnaires do not consider individual preferences, which
      therefore need to be addressed in the dialogue with the patient. QoL assessment
      is clearly in need of further methodological improvement before this endpoint can
      be regarded as fully established with respect to ability to provide unequivocally
      useful data in clinical trials. The multitude of questionnaires, missing data,
      lack of pre-study hypotheses of relevant differences between treatments and data
      multiplicity giving a risk for chance findings are examples of serious
      methodological problems. Patient response-shifts over time further complicate the
      interpretation of the data. Thus, QoL data, also from seemingly well-performed
      clinical trials, have to be interpreted cautiously. The international development
      during recent years has aimed at creating increased standardization of QoL
      measures. This has created greater possibilities to compare results from
      different trials. Hopefully, this also implies that it will be possible to draw
      firmer conclusions from QoL measurements in recently completed or ongoing trials
      than has been the case previously. QoL assessments are resource demanding even
      when short standardized questionnaires are used. Since cancer patients also
      generally give priority to anticancer effects over toxicity and convenience, QoL
      assessments in clinical trials are motivated mainly in study settings comparing
      treatments without expected major differences of outcome in objective endpoints.

PMID- 11441931
TI  - A systematic overview of chemotherapy effects in Hodgkin's disease.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on
      chemotherapy for Hodgkin's disease (HD) is based on 113 scientific reports
      including four meta-analyses, 44 randomised studies, 18 prospective studies and
      40 retrospective studies. These studies involve 69,196 patients. The conclusions
      reached can be summarised into the following points: Chemotherapy is of utmost
      importance for the cure of HD. At early stages, extended field radiotherapy cures
      most patients. For the majority of patients with relapse after radiotherapy,
      chemotherapy is curative and the total proportion of cured early stage patients
      is 75-90%. Chemotherapy in addition to extended field radiotherapy reduces
      recurrences but does not improve long-term survival. In early stage HD with a
      large mediastinal mass and/or with systemic symptoms, combined treatment with
      chemotherapy and radiotherapy is recommended. It is likely that chemotherapy will
      play a greater role in the future in the treatment also of early stage patients
      in order to reduce late consequences from extended field radiotherapy. However,
      this conclusion remains to be better documented in the literature. At advanced
      stages, chemotherapy or a combination of chemotherapy and limited field
      radiotherapy are effective treatment options and, using the regimens available 10
      20 years ago, 40-50% of the patients are cured. Based upon more favourable short
      term (three to eight years) results of more recently developed regimens, it can
      be expected that today a higher proportion of the patients will become long-term
      survivors. Several chemotherapy regimens containing four to eight drugs are
      effective in HD. The best regimen considering both antitumour activity and acute
      and late side-effects is not known. The choice of regimen is probably best done
      after considering various pre-treatment factors such as the number of poor
      prognostic signs, concomitant diseases and individual preferences. The results of
      chemotherapy are more favourable in young than in elderly patients. The
      development of less toxic but still effective treatment programmes is therefore
      particularly important for the elderly. High dose chemotherapy with stem cell
      support is presently often used in patients who are chemotherapy induction
      failures, who relapse after a short initial remission or after a longer initial
      remission and treated initially with seven or eight drugs, or who have had
      multiple relapses. However, this use is based on data from uncontrolled or small
      controlled studies, not being fully convincing with respect to effect on
      survival. Persistent side-effects of treatment are common among long-term
      survivors, although most patients have an apparently normal life. The relative
      contributions of chemotherapy and radiotherapy to the persistent effects are not
      well documented.

PMID- 11441932
TI  - A systematic overview of chemotherapy effects in aggressive non-Hodgkin's
      lymphoma.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on
      aggressive, high grade non-Hodgkin's lymphoma (NHL), chiefly diffuse large B-cell
      lymphomas, is based on 111 scientific articles, including 35 randomised trials,
      44 prospective studies and 11 retrospective studies, including totally 21,830
      treated patients. The conclusions reached can be summarised into the following
      points: For patients with localised aggressive NHL (stage I and non-bulky II) a
      combination of chemo- and radiotherapy will result in cure for a large proportion
      of patients. For a subgroup of patients with stage I non-bulky disease and
      without risk factors, local radiotherapy alone is also adequate treatment. For
      patients with disseminated aggressive NHL, including the elderly, the CHOP
      regimen remains the standard primary chemotherapy. In an unselected population,
      this treatment cures about one third of the patients. For most patients with poor
      prognostic factors, CHOP provides insufficient results. The results of therapy
      with dose-intensive combinations of cytotoxic drugs have been conflicting. Most
      randomised studies, using intensive regimens as first line therapy, have failed
      to show any benefit in comparison to CHOP. However, it is possible that regimens
      other than CHOP might be more beneficial in subgroups with 'high risk' disease.
      This remains to be investigated in prospective studies. In young, poor prognosis,
      patients a further intensified induction therapy requiring haematopetic stem cell
      support, i.e. high dose therapy, has been suggested to be beneficial. The best
      results have been reported from studies with full course standard induction
      followed by high-dose therapy. However, the study data are conflicting, which is
      why additional controlled studies are recommended. In patients refractory to or
      relapsing after initial therapy, different chemotherapy combinations may induce a
      new response. The responses are, however, rather short-lived and long-term
      survival is rarely seen. In patients not attaining complete remission after
      initial standard therapy, high-dose therapy with stem cell support may improve
      the response, but the impact on survival is not established. In patients
      refractory to initial standard therapy there is no evidence for a survival
      prolongation from high-dose therapy with stem cell support, although a subset of
      patients might benefit. For patients with chemosensitive relapse, salvage therapy
      followed by high-dose therapy with stem cell support is recommended, since this
      may result in prolonged survival.

PMID- 11441933
TI  - A systematic overview of chemotherapy effects in indolent non-Hodgkin's lymphoma.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for evaluation the scientific literature are described separately
      (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy
      for indolent non-Hodgkin's lymphoma (NHL), predominantly follicular lymphoma, is
      based on 108 scientific reports including 31 randomised studies, 38 prospective
      studies and 18 retrospective studies. These studies involve 8,699 patients. The
      conclusions reached can be summarized into the following points: In initially
      localized disease-- The addition of chemotherapy to radiotherapy as primary
      treatment has not convincingly prolonged remission duration or survival. In
      initially advanced disease-- Alkylating agents are useful palliative treatment
      options which can result in improved well-being for most patients, often for long
      periods. Combinations of chemotherapy have not convincingly resulted in more or
      longer remissions. There is no proof that initial combination chemotherapy will
      prolong survival in comparison with single drugs. The addition of interferon to
      initial combination chemotherapy may increase the response rate, significantly
      prolong remission duration, but prolonged survival has not been unequivocally
      proven. In the absence of disease-related symptoms, treatment can safely be
      deferred. For patients with relapsed lymphoma-- Patients may repeatedly respond
      to alkylating agents or combinations containing an alkylating agent, although the
      proportion responding decreases with each relapse. Patients relapsing after or
      who are refractory to treatment with alkylating agents often respond to treatment
      with combinations containing an anthracycline. Responses are also often seen in
      patients treated with purine analogues alone or in combination with other drugs.
      High dose chemotherapy followed by autologous or allogeneic reestablishment of
      bone marrow function can induce long-term remissions but it is not proven whether
      they are more frequent or of longer duration than with conventionally dosed
      therapy. The impact of the novel treatment strategies including high-dose therapy
      on overall survival is still uncertain. A monoclonal antibody, rituximab, is a
      new active substance for patients with relapsed lymphoma. It can induce
      remissions also in chemoresistant patients.

PMID- 11441934
TI  - A systematic overview of chemotherapy effects in B-cell chronic lymphocytic
      leukaemia.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on
      chemotherapy for B-cell chronic lymphocytic leukaemia (B-CLL) is based on data
      from 20 randomised controlled trials and one meta-analysis. Moreover, data from
      19 prospective studies, one retrospective study and four other articles were
      used. Totally 44 scientific articles are included, involving 11,289 patients. The
      conclusions reached can be summarized into the following points: Primary
      treatment of patients with symptomatic B-CLL is recommended to be an oral
      alkylating agent such as chlorambucil. This drug induces tumour remission and
      symptomatic relief in a majority of patients with progressive disease. Response
      may be long-lasting, but cure is not obtained. Optimum dose and schedule of
      administration of chlorambucil or other alkylating agents have not been defined.
      It is recommended to defer initial therapy until required by disease progression.
      Large randomised trials have demonstrated that early treatment with chlorambucil
      in a continuous or an intermittent schedule does not prolong survival in B-CLL
      patients with low tumour burden (Binet stage A). The addition of corticosteroids
      to alkylator regimens has not been proven to give any benefit. Combination
      chemotherapy as primary treatment has not shown any advantage compared with
      single drugs. Early inclusion of anthracyclines to the therapy does not
      convincingly add to the activity of alkylating agents. The purine analogues
      fludarabine and 2-chlorodeoxyadenosine are active in B-CLL. However, like other
      drugs, they do not appear to be curative. In randomised multicentre trials a
      benefit from fludarabine as primary therapy compared with polychemotherapy (CHOP
      or CAP) has been observed in terms of tolerance and treatment response but not
      yet in survival. No randomised studies have been performed to show whether one of
      the purine analogues should be preferred. At relapse after single drug treatment,
      retreatment with the same drug often induces new remissions. However, the
      proportion of patients responding declines each time chlorambucil or any other
      single agent is readministered. At progression on single alkylating agents, the
      purine analogues or various combinations, mostly CHOP, frequently induce tumour
      remissions. For patients with advanced B-CLL failing to respond to fludarabine or
      CHOP, the prognosis is poor. None of the salvage regimens reported has produced
      durable remissions. High-dose chemo-radiotherapy with stem cell transplantation
      has been evaluated for young patients with B-CLL. A long survival has been shown
      in some patients following allogeneic and autologous transplantation. However,
      the risk of transplantation-related mortality is still high with allo-transplants
      and relapse is common after auto-transplantation. A benefit of purging autologous
      stem cells has been proposed but evidence is lacking. Thus, transplantation
      remains experimental; more patients and a longer follow-up are needed to assess
      if cure can be achieved. In the future an individual risk-adapted therapy will be
      required. The clinical heterogeneity of the disease has pointed to the necessity
      of new predictors for prognosis evaluated in prospective trials.

PMID- 11441935
TI  - A systematic overview of chemotherapy effects in acute myeloid leukaemia.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on
      chemotherapy in patients with acute myeloid leukaemia (AML) is based on 129
      scientific articles: one meta-analysis, 51 randomised trials, 39 prospective and
      18 retrospective studies, and 20 other articles. Altogether, 39,557 patients were
      included in these studies. The conclusions reached can be summarized into the
      following points: Standard induction therapy for patients with AML, consisting of
      daunorubicin and ara-C in conventional doses, results in a complete remission
      (CR) rate of 50-60% in an unselected population and a long-term survival of about
      10-20%. The total doses of both ara-C and daunorubicin are of importance for
      remission duration and in some studies also for survival. High-dose ara-C in the
      induction therapy prolongs remission duration in randomised trials, but has not
      been proven to affect long-term survival. It also increases toxicity and is not
      generally recommended. Idarubicin, another anthracyclin, has been compared with
      daunorubicin in conjunction with ara-C, resulting in a higher CR rate, especially
      in younger patients. In a meta-analysis of the five-randomised trials performed,
      a slight survival advantage was also seen with idarubicin. Yet, there is
      inconclusive evidence to conclude that idarubicin is superior to daunorubicin,
      and further trials are needed. Mitoxantrone improves the outcome of induction
      therapy in comparison with daunorubicin in some randomised studies, but
      conclusive evidence is still lacking. The addition of etoposide to daunorubicin
      or mitoxantrone and ara-C has improved CR rates, but has not convincingly
      improved survival and secondary leukaemias may be induced. New induction
      treatment strategies are defined by identification of prognostic subgroups. A
      risk stratification of AML patients as to chromosomal aberrations might be of
      importance for the choice of therapy. Moreover, the speed and the morphological
      response to the first induction course are predictive for relapse. However, no
      prospective randomised studies are as yet published regarding risk-adapted
      induction therapy. Post-remission dose-intensive chemotherapy prolongs the
      duration of remission, seemingly most in patients < 60 years. However, the data
      in support of these conclusions are sparse. A convincing effect on survival has
      not been shown. Limited data indicate that post-remission maintenance therapy
      with long-term attenuated chemotherapy prolongs time to recurrence, without
      evidence for prolongation of survival. Allogeneic bone marrow transplantation is
      an established practice for consolidation in first remission for young patients
      with an HLA-matched sibling. It is however not known which patients will really
      benefit from transplantation as no truly randomised comparison of allogeneic vs
      autologous transplantation or conventionally-dosed chemotherapy has been
      performed. Patients with and without an HLA-identical sibling have been compared
      on the basis of intention-to-treat principles ('genetic randomisation'). The
      disease-free survival seems to be prolonged in the donor group, due to a lower
      relapse rate with allogeneic transplantation. A higher procedure-related
      mortality makes the effects on total survival uncertain. Randomised trials with
      autologous transplantation vs conventional consolidation show a lower relapse
      rate and a trend for an improved disease-free survival. In one study, in which an
      autograft was added to four courses of intensive therapy, there was also a late
      survival advantage. Thus, the role for intensified post-remission treatment in
      first complete remission with high-dose chemotherapy followed by allogeneic or
      autologous marrow or stem cell transplantation requires further studies.
      Moreover, studies with stratification of therapy according to predictors for
      prognosis in the individual patient are needed. Allogeneic stem cell
      transplantation after minimal or reduced myeloablative conditioning ('mini
      transplantation' or non-myelo stem cell transplantation) induces a host-vs-graft
      tolerance and an immune graft-vs-leukaemia effect. This new concept of
      immunotherapy seems to have a low procedure-related mortality, but long-term
      effects are unknown and evaluation in controlled clinical studies is required.
      Patients with relapsed AML can only infrequently achieve long-term remissions
      with chemotherapy in conventional doses. trolled data indicate that allogeneic
      transplantation can be a curative treatment for these patients a

PMID- 11441936
TI  - A systematic overview of chemotherapy effects in breast cancer.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on
      chemotherapy for breast cancer is based on 233 randomised studies, 9 meta
      analysis of randomised studies, a population-based cohort study and 18
      overviews/retrospective analyses including a total of 155,243 patients. The
      conclusions reached can be summarised into the following points: Adjuvant
      treatment-- There is solid scientific support from randomised studies that
      adjuvant polychemotherapy at 10 years will result in an absolute mortality
      reduction for patients younger than 50 years by 12% for node positive (34%
      relative mortality reduction corresponding to an estimated median survival
      prolongation of several years) and 6% for node negative patients. For women aged
      50 to 69 years, the corresponding figures for node positive and node negative
      patients are 6% and 2%, respectively (approximately 11% relative mortality
      reduction). Anthracycline-containing combinations result in an absolute survival
      benefit at five years of 3%, compared with non-anthracycline based
      polychemotherapy. There are indications that the taxane paclitaxel may further
      improve the survival compared with anthracyclines. However, the limited data
      preclude conclusions for the routine care. The addition of tamoxifen to
      chemotherapy further enhances the survival benefit for receptor positive
      subgroups. The roles of more dose-intensive regimens, including high-dose therapy
      with stem cell support, are presently studied in randomised investigations. The
      data presented so far are conflicting but they do not in general support high
      dose therapy. Quality of life, based on analyses of randomised studies,
      demonstrate that adjuvant polychemotherapy has an initial detrimental effect, but
      long-term follow-up of treated patients demonstrates no impairment of quality of
      life compared with untreated patients. Polychemotherapy in standard doses should
      be offered to premenopausal node positive patients, and the corresponding
      postmenopausal group with a receptor-negative breast cancer and to node negative
      patients with high risk factors. Polychemotherapy should be combined with
      tamoxifen to all patients with receptor-positive tumours. Due to a need of more
      knowledge in this field, patients should be included in investigational
      protocols. Locally advanced breast cancer-- Based on current knowledge, treatment
      of patients with locally advanced breast cancer should include
      neoadjuvant/preoperative polychemotherapy since there is evidence from controlled
      studies that such therapy will statistically significantly increase the number of
      patients who can be offered breast-conserving surgery. Indirect comparisons also
      demonstrate survival improvements, but the scientific support is equivocal.
      Metastatic breast cancer-- The median survival for patients with metastatic
      disease treated with conventional chemotherapy doses and regimens is 12 to 24
      months. Retrospective cohort studies indicate that the use of non-anthracycline
      containing chemotherapy compared with no chemotherapy might add a survival gain
      of six to nine months. However, this estimation is based on equivocal data. Based
      on overview data, polychemotherapy results in a statistically significant
      survival gain compared with single-agent therapy. Based on repeated randomised
      studies, the addition of anthracyclines increases the response rate and
      statistically significantly improves the survival compared with non-anthracycline
      containing chemotherapy, except for CMF combined with prednisone/prednisolone,
      which will statistically significantly improve the survival compared with some
      anthracycline combinations. Second line therapy using vinorelbine or docetaxel is
      statistically significantly better than other regimens with a time to progression
      and survival benefit in the order of one to three months based on few randomised
      studies. The role, if any, of third line therapy is yet to be demonstrated. In
      the metastatic setting, conventional chemotherapy improves the quality of life.
      In standard care, first line therapy should contain an anthracycline and second
      line therapy using vinorelbine or docetaxel could be offered to selected patients
      failing first line therapy. Based on numerous randomised studies, breast cancer
      demonstrates a positive dose-response relationship both in the adjuvant situation
      and for metastatic disease. However, in the conventional dose-range there seems
      to be a plateau in the dose-response curve, with no further survival gains for
      high

PMID- 11441937
TI  - A systematic overview of chemotherapy effects in colorectal cancer.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on
      adjuvant and palliative therapy with cytostatics for colorectal cancer is based
      on 208 scientific articles, including eight meta-analyses and 162 randomised
      studies. These studies involve approximately 126,800 patients. The conclusions
      reached can be summarized into the following points: The benefit of postoperative
      adjuvant chemotherapy with fluorouracil and levamisole in patients with colon
      cancer stage Dukes' C was demonstrated more than ten years ago in two phase III
      trials. There was a reduction of recurrence from 56% to 39% and reduction of
      death from 51% to 40% after more than five years of follow-up. Although this
      combination has been widely accepted as standard adjuvant treatments for stage
      Dukes' C colon cancer, there is still debate on whether adjuvant treatment with
      fluorouracil alone would be equally efficacious. Several phase III trials with
      postoperative adjuvant chemotherapy with fluorouracil and leucovorin in patients
      with colon cancer stage Dukes' C have demonstrated a similar statistically
      significant improvement in disease-free and overall survival in comparison with a
      control arm. Six months of treatment with fluorouracil and leucovorin is as
      efficient as twelve months of fluorouracil and levamisole. This treatment is,
      thus, recommended for routine use. No convincing benefit from adjuvant
      chemotherapy is proven in colon cancer stage Dukes' B although some randomised
      trials have shown the same relative survival gain as seen in stage Dukes' C.
      There is less knowledge on survival benefits from adjuvant chemotherapy for
      Dukes' stage B and C rectal cancer. In small randomised trials, postoperative
      radiochemotherapy has, however, improved survival to the same extent as
      chemotherapy in colon cancer Dukes' stage C. A meta-analysis of nine randomised
      trials revealed a small but statistically significant benefit in five-year
      survival and a reduction in the risk of death for the patients receiving
      immediate postoperative portal vein infusion compared with controls. At present,
      however, the use of portal vein infusion or intraperitoneal therapy outside of a
      research trial cannot be recommended in the light of the limited effects. This
      conclusion is further supported by similarly limited effects in two recently
      reported very large European multicentre trials. In advanced colorectal cancer,
      chemotherapy may prolong survival, decrease tumour-related symptoms, improve
      general well-being or maintain it at a high level for a longer time period
      compared with best supportive care. These effects have been seen using systemic
      chemotherapy and using regional chemotherapy in patients with metastases limited
      to the liver. Subjective responses and quality of life improvements are seen more
      frequently than objective tumour remissions. Although the impact on overall
      survival is modest, i.e. an improvement in median survival of five to six months,
      treatment is recommended also outside clinical trials. High-dose infusional
      regimens with modulated fluorouracil may turn out to be superior to conventional
      bolus regimens, since they result in more tumour regressions, longer times to
      disease progression and possibly longer survival. A plateau seems, however, to
      have been reached with fluorouracil, giving objective response rates of up to 30%
      to 40% with a variety of modulators. Randomised studies of regional therapy,
      mostly hepatic arterial infusions, of liver metastases in colorectal patients
      have demonstrated significantly higher response rates than systemic fluorouracil
      therapy alone without impact on overall survival. The importance of the higher
      response rates for patient benefit in the predominantly asymptomatic patients
      with isolated liver metastasis remains to be elucidated. Regional therapy in
      advanced disease cannot be recommended outside of clinical trials. New cytotoxic
      agents are emerging with antitumour activity similar to fluorouracil-based
      chemotherapy. The addition of oxaliplatin or irinotecan to existing fluorouracil
      regimens improves response rates and duration of response, and possibly overall
      survival. Based upon the results of two randomised studies, there is a role for
      irinotecan as second line therapy for selected patients who have failed first
      line therapy with fluorouracil plus leucovorin. The role of these agents, alone
      or in combinations, in clinical routine remains, however, to be determined due to
      more pronounced toxicity than caused b

PMID- 11441938
TI  - A systematic overview of chemotherapy effects in gastric cancer.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on
      chemotherapy in the treatment of gastric cancer is based on 153 scientific papers
      including one meta-analysis, 18 reviews, 60 randomised studies and 57 prospective
      studies. The trials consist of 12,367 patients. The conclusions reached can be
      summarized into the following points: A meta-analysis of 21 randomised adjuvant
      studies revealed a statistically significant survival benefit. The Odds Ratio
      (OR) is 0.84 (95% confidence interval, 95% CI, 0.74-0.96). However, by analysing
      Western world and Asian studies separately, a statistically significant
      difference can be noticed; the Western world studies showed an OR of 0.96 (95% CI
      0.83-1.12) and the Asian an OR of 0.58 (95% CI 0.44-0.76). The cause of this
      difference is not apparent. There is not sufficient evidence to recommend
      adjuvant chemotherapy as routine treatment in the Western world. Preoperative
      chemotherapy given to patients with non-resectable tumours or locally advanced
      potentially resectable tumours has achieved resectability rates of 40-100% and
      potentially curative resections in 37-80%. One out of two randomised studies
      showed a significant survival benefit, but reported data are not convincing.
      Experimental data in favour of preoperative therapy has not yet been confirmed in
      randomised clinical studies. Therapy is only justified in controlled clinical
      trials. Published studies on the use of intraperitoneal chemotherapy are few and
      not conclusive regarding the efficiency and safety. This method of drug
      administration is, accordingly, justified only in controlled clinical trials. In
      advanced gastric cancer, phase II studies have indicated better response rates
      using drug combinations than using single drug regimens, differences that have
      not, however, been convincingly demonstrated in randomised studies. No firm
      conclusions can be drawn regarding the superiority for any of the studied drug
      combinations with respect to response or survival gain. A statistically
      significant survival benefit has been shown in trials comparing drug combinations
      with a best supportive care arm in the treatment of advanced gastric cancer.
      However, the number of included patients is small. The median survival benefit in
      advanced disease is in the range of three to nine months. The use of chemotherapy
      in advanced gastric cancer is justified in selected patients, e.g. in younger
      patients in good performance status, low tumour burden and no other serious
      medical condition after adequate information of potential gains and risks. The
      influence of chemotherapy on quality of life in advanced gastric cancer has been
      reported in only a few studies. It appears that about 50% of the patients have a
      clinically relevant relief of tumour-related symptoms and thereby improved
      quality of life. In one study, quality-adjusted survival was estimated to a
      median of six months in the treated patients compared with two months in the
      controls. The quality of the literature addressing chemotherapy for gastric
      cancer is frequently poor with few properly designed randomised trials. In a
      number of randomised multi-centre adjuvant studies the inclusions rates are
      remarkably low, which reduces the scientific value of the studies.

PMID- 11441939
TI  - A systematic overview of chemotherapy effects in non-small cell lung cancer.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on
      chemotherapy for non-small cell lung cancer (NSCLC) is based on 53 scientific
      publications including six meta-analyses based on 65 prospective randomised
      trials comprising 15,607 patients and an additional 32 prospective randomised
      studies including 8,902 patients. The conclusions reached can be summarised into
      the following points: In stage IIIB-IV disease, published data demonstrate that
      cisplatin-based chemotherapy confers a modest, median 1.5-3 months, prolongation
      of survival. The closely related compound carboplatin seems to provide similar
      effects. Randomised studies indicate symptomatic relief and improvement of
      indices of quality of life (QoL) for patients who receive platinum-based
      combination chemotherapy or single drug therapy with more recent compounds. Data
      supporting the use of chemotherapy are not available for patients in poor general
      condition (WHO performance status 3 4) and evidence is limited for elderly
      patients (above 70-75 years). Platinum-based chemotherapy can be recommended for
      selective use in routine care of advanced NSCLC although patients should be
      encouraged to participate in controlled clinical trials to further elucidate the
      role of chemotherapy in advanced disease. In advanced disease, recent data
      suggest that the newer agents gemcitabine, paclitaxel, irinotecan and
      vinorelbine, in combination with cisplatin, provide an additional survival
      benefit compared with earlier cisplatin-based regimens. Furthermore, paclitaxel,
      docetaxel and vinorelbine as single agents seemingly provide a survival benefit
      over supportive care alone comparable to that of older cisplatin-based
      combinations. A standard regimen for advanced disease cannot yet be defined.
      Until more data are at hand, it is recommended to be platinum-based and
      preferably combined with one of the newer agents. At progression after platinum
      based chemotherapy for advanced disease, limited data indicate a small survival
      benefit from docetaxel over supportive care alone. Such second-line chemotherapy
      of advanced disease can be recommended for selected patients but should
      preferably be confined to controlled clinical trials. In stage III disease,
      published data show that induction cisplatin-based chemotherapy before radical
      radiotherapy modestly prolongs long-term survival and lowers the incidence of
      distant metastases compared with radiotherapy alone. Furthermore, published data
      show that concurrent chemo- and radiotherapy with cisplatin or carboplatin may
      enhance local control and long-term survival. Chemotherapy in this setting can be
      recommended for selected patients but treatment should preferably be given within
      a controlled clinical trial. In stage IIIAN2 disease, data from pilot studies
      demonstrate that surgery after induction chemotherapy is feasible. Pathologically
      complete remissions have been confirmed in 10-20% of treated patients. Two small
      randomised studies demonstrate a significant survival advantage for induction
      chemotherapy followed by surgery compared with surgery alone. Induction
      chemotherapy can be recommended for selected patients but treatment should
      preferably be given within a controlled clinical trial. The superiority of
      induction chemotherapy plus surgery compared with combined chemotherapy and
      radical irradiation has not been proven in a randomised trial but currently such
      studies are under way. In the adjuvant setting, published data suggest that
      cisplatin-based chemotherapy after radical surgery may increase five-year
      survival from around 50% by a further 5% but the confidence interval for this
      estimate is too wide for firm conclusions. Large-scale prospective randomised
      trials are under way to resolve this important issue and adjuvant chemotherapy
      is, thus, not recommended for routine treatment.

PMID- 11441940
TI  - A systematic overview of chemotherapy effects in ovarian cancer.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This overview on chemotherapy for
      epithelial ovarian cancer is based on a total of 176 scientific reports. Five
      meta-analyses including 17,291 patients, 33 prospective randomised studies
      including 12,340 patients, 36 prospective studies including 3,593 patients and
      one retrospective study including 421 patients. The studies include approximately
      33,642 patients. The conclusions reached can be summarized into the following
      points: Radically operated patients with low-risk early ovarian cancer (stage IA
      or IB non-clear-cell well-differentiated carcinomas or borderline tumours) have a
      very good prognosis and there is no indication for adjuvant therapy. Radically
      operated patients with high-risk early ovarian cancer (clear cell carcinomas or
      FIGO stage IA or IB moderately or poorly differentiated carcinomas or stage IC)
      have a substantial risk for micrometastatic disease. However, the role of
      adjuvant chemotherapy is unclear and such therapy should, thus, only be used
      within clinical trials. The median overall survival for patients with advanced
      (FIGO stages II-IV) ovarian cancer randomised to paclitaxel/platinum-containing
      chemotherapy in three large studies ranged between 36-39 months. Compared with
      historical data, this represents a six to seven times longer median survival time
      than after surgery only. The probability for long-term survival for patients
      treated with a paclitaxel/platinum combination is too early to define. In two
      prospective randomised trials in advanced ovarian cancer, paclitaxel in
      combination with cisplatin has provided a survival benefit over
      cyclophosphamide/cisplatin. Based on these trials, paclitaxel/cisplatin is
      considered to be the standard treatment. This choice of standard therapy might,
      however, be questioned based on the results of the hitherto largest randomised
      study in advanced ovarian cancer, ICON3, which is, as yet only available in
      abstract form. It compared paclitaxel/carboplatin with carboplatin only or a
      platinum combination (cyclophosphamide/doxorubicin/cisplatin). There were no
      statistically significant differences in progression-free or overall survival.
      The drug regimen in the control arms of the previous studies showing superiority
      of the paclitaxel-cisplatin combination may not have been the optimal non
      paclitaxel platinum-containing regimen. Three randomised studies have compared
      carboplatin/paclitaxel with cisplatin/paclitaxel. All three are hitherto only
      published as abstracts with short follow-up precluding survival analyses. None of
      them shows any difference in response rates. All three show less toxicity and one
      also better quality of life with carboplatin. Thus, there are preliminary data
      supporting the substitution of cisplatin with carboplatin. Intraperitoneal
      therapy with cisplatin caused improved survival compared with intravenous therapy
      in one ramdomised study. Further studies have shown trends to better survival and
      longer progression-free interval with intraperitoneal therapy. The accrual to
      studies on intraperitoneal chemotherapy has been poor reflecting that it is a
      cumbersome and not easily accepted treatment. In advanced ovarian cancer, no
      convincing advantage has been shown from more dose-intensive chemotherapy,
      without cytokines or bone marrow stem cell support, compared with standard doses.
      High response rates are achieved with high-dose chemotherapy with stem cell
      support in the salvage situation but response duration is short. Phase III
      studies evaluating high-dose chemotherapy in the first-line situation are
      ongoing. Until supportive controlled clinical trials are presented, high-dose
      chemotherapy should be confined to clinical trials. Tumour response is frequently
      observed on re-treatment with the same drugs as given first-line in patients
      sensitive to first-line platinum-based chemotherapy with a long progression-free
      interval. Thus, in these patients treatment with a platinum/paclitaxel
      combination might be recommended. albeit based on limited data. In patients
      resistant to first-line therapy, a number of single agents induce tumour
      responses in the range of 10-30%. The literature does not permit general
      treatment recommendations in these patients, which are recommended to be included
      in controlled clinical trials.

PMID- 11441941
TI  - A systematic overview of chemotherapy effects in pancreatic cancer.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40:155-65). The conclusions of this overview in
      pancreatic cancer are based on 10 randomised studies with, and 18 randomised
      studies without, an untreated control group. Altogether, 4,028 patients were
      included in the phase III studies. Furthermore, 32 phase II studies or
      retrospective analyses including 1,404 patients have been evaluated. The
      conclusions reached can be summarized into the following points: There is no
      convincing evidence that pancreatic cancer patients benefit from adjuvant
      chemotherapy treatment, with or without concomitant radiotherapy. Adjuvant
      chemotherapy in patients with pancreatic cancer should thus not be used
      routinely. In locally advanced/metastatic pancreatic cancer, six randomised
      trials comparing combination chemotherapy with an untreated control group were
      retrieved. In three trials, two of which were performed recently, chemotherapy
      provided statistically significant prolongation in median survival in the range
      of three to nine months. The three other trials, all reported in the early 80s,
      essentially showed no difference in survival between the treatment groups. In the
      locally advanced/metastatic setting there are also several randomised trials
      comparing various chemotherapy regimens. Except for an improvement in median
      survival of one to two months from gemcitabine compared with 5-FU, no differences
      were observed. There is no convincing evidence that a large fraction of
      pancreatic cancer patients will benefit from palliative chemotherapy. The few
      open-design studies that have explored the influence on symptom relief/quality of
      life indicate that between 20-35% of the patients get clinical benefit, but
      usually short-lived. Recently performed randomised studies, all using adequate
      methodology, indicate that the beneficial effects observed in advanced pancreatic
      cancer are similar to those of accepted therapy in other cancer types. However,
      due to the limited positive effects, palliative chemotherapy in pancreatic cancer
      can only be recommended selectively and should preferably be used within
      controlled clinical trials exploring new treatment combinations or concepts.

PMID- 11441942
TI  - A systematic overview of chemotherapy effects in urothelial bladder cancer.
AB  - A systematic review of chemotherapy trials in several tumour types was performed
      by The Swedish Council of Technology Assessment in Health Care (SBU). The
      procedures for the evaluation of the scientific literature are described
      separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on
      chemotherapy for urothelial bladder cancer is based on 234 scientific reports
      including two meta-analyses, 75 randomised studies and 143 other prospective
      studies, and totally comprising 31,974 patients. The conclusions reached can be
      summarised into the following points: Intravesical chemotherapy administered in
      an adjuvant setting to transurethral resection (TUR-B) of superficial tumour
      reduces short-term (one to three years) recurrence rate by approximately 20%.
      After a median follow-up of eight years, 8%, fewer recurrences were seen after
      intravesical chemotherapy. Long-term maintenance instillation chemotherapy ( > 1
      year) does not further increase the recurrence-free interval nor the long-term
      recurrence rate when compared with immediate postoperative short-term
      intravesical chemotherapy. The majority of studies on intravesical Bacillus
      Calmette-Guerin (BCG) vs intravesical chemotherapy show superior protection from
      tumour recurrence for BCG. Despite prolongation of the disease-free survival,
      adjuvant intravesical chemotherapy has, in the majority of studies, no apparent
      long-term impact on the evolution of superficial into muscle invasive bladder
      cancer. There are no data showing a survival benefit from adjuvant intravesical
      chemotherapy. Chemotherapy with cisplatin-based regimens induce objective tumour
      response in at least 50% of patients with metastatic disease. A prolonged disease
      free and overall survival (median two to three months) is seen in patients
      treated with cisplatin-based polychemotherapy compared with patients treated with
      cisplatin alone or less intensive chemotherapy. With the exception of one
      randomised study, there are no conclusive data on possible survival benefit for
      patients with muscle-invasive bladder cancer treated with neoadjuvant
      chemotherapy prior to cystectomy or radiotherapy. Although the results from use
      of adjuvant chemotherapy after surgery or curative radiotherapy obtained are
      promising, the small studies performed lack statistical power and, hence, there
      is insufficient data to make any conclusion regarding a possible survival benefit
      from adjuvant chemotherapy. A growing body of data indicate that bladder
      preservation can be achieved by multi-modality approach in selected patients and
      that survival in these is similar to that seen after radical cystectomy, but
      randomised trials are still lacking.

PMID- 11441943
TI  - A prospective study of the use of chemotherapy in Sweden and assessment of the
      use in relation to scientific evidence.
AB  - A prospective study on total utilisation of cytotoxic drugs for selected cancers
      was carried out in two Swedish health service regions, during four weeks in the
      autumn of 1997. The study included 1,590 patients; 1,169 with solid tumours and
      421 with haematological malignancies. The majority of patients (75% to 80%) were
      treated at university/regional hospitals, often at oncology or haematology
      departments, and most received treatment as outpatients. Furthermore, most were
      treated according to recommendations in regional or national clinical guidelines,
      so-called care programmes, although the percentage varied by diagnosis. Only 10%
      were participants in a clinical trial. In approximately 40% of the patients,
      treatment was aimed at cure. However, this percentage varied between 0% and 94%
      depending on tumour type. At the population level, a comparison of the scientific
      evidence according to a literature review (Acta Oncol, this issue) with the
      survey showed that treatment with cytotoxic drugs in Sweden was largely evidence
      based. A high percentage of patients received cytotoxic drugs for diseases where
      recommendations to treat were strong, i.e. outcomes were well-documented in the
      literature. A low percentage of patients received chemotherapy in disease
      settings with little or no scientific documentation. The percentage of patients
      treated was also limited in cases where the effects of chemotherapy are
      relatively small, although scientifically well-documented. For methodological
      reasons, one cannot exclude the possibility that cytotoxic drugs may be
      overutilised at the individual level for palliative purposes, e.g. by not
      discontinuing treatment despite the absence of clinical benefits. Likewise, one
      cannot exclude the possibility of underutilisation, e.g. by patients declining
      treatment because they were not informed about the potential benefits.

PMID- 11441944
TI  - Economic aspects of chemotherapy.
AB  - A systematic review of the effect of chemotherapy in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The review also included an assessment of the limited number of studies available
      on the health economics of chemotherapy for diagnoses included in the SBU report.
      The conclusions reached from this assessment can be summarized as follows:
      Several international studies and one Swedish study addressed the cost
      effectiveness of different chemotherapeutic regimens. The quality of the studies
      is generally low and comparability is rather limited. Some of the studies
      compared cytostatic treatment with no cytostatic treatment. Most studies,
      however, compared two or more treatments. The costs were then compared with
      potential differences in treatment outcome. Outcomes are mostly measured as the
      cost per life-year gained. The results from these studies vary by treatment and
      indication. In some cases, after all relevant costs are taken into account,
      chemotherapy shows cost savings. In most studies, chemotherapy is associated both
      with higher costs and improved treatment results, often measured in terms of
      survival. Studies of rather high quality show that the cost per life-year gained
      (quality-adjusted) for most chemotherapeutic regimens with relatively limited
      effects ranges between 100,000 and 250,000 Swedish kronor (SEK). Estimates of
      cost-effectiveness for more effective chemotherapy has not been reported in the
      literature. The estimated costs are in parity with the costs of 'established'
      treatments for other diseases. There is uncertainty about what treatments can be
      considered cost-effective; there is no consensus concerning what costs are
      'reasonable' per life-year gained in health care. The estimates of cost
      effectiveness in most studies are highly uncertain and must be interpreted with
      caution. Improved assessment would require more studies in Sweden. For various
      reasons it is difficult to apply the results from the international studies to
      Sweden.

PMID- 11441945
TI  - Microscopic distribution of iodine radioisotopes in the thyroid of the iodine
      deficient new-born rat: insight concerning the Chernobyl accident.
AB  - Thyroid cancer markedly increased in children exposed to iodine radioisotopes
      following the Chernobyl accident. This increase exceeded predictions based on
      dose estimates to the whole organ. We sought to investigate whether iodine
      deficiency may have influenced the pattern of microscopic distribution of
      radioiodines, which may be important to interpretation of the observed effects.
      Iodine-deficient new-born rats were injected with iodine-129 (129I) and the
      microscopic distribution in the thyroid tissue was studied at 24 hr and at one
      week after administration, using secondary ion mass spectrometry (SIMS). Twenty
      four hr after administration, SIMS images showed large differences in 129I uptake
      among thyroid follicles, with more than a factor ten variation in the local
      concentration. In addition, the distribution of 129I inside follicles varied with
      time. At 24 hr, the highest concentration was found at the periphery of the
      colloid, close to the thyroid cells. There also was enhanced concentration of
      129I at one pole of follicles. Distribution inside follicles was homogeneous at 7
      days. CONCLUSIONS: 1/Dosimetric models, which assume uniform iodine uptake by
      thyroid follicles, give an oversimplified picture of radiation dosimetry in cases
      involving iodine deficiency, which induces patchy tissue irradiation. 2/The
      dynamic pattern of iodine distribution within thyroid follicles suggests that
      decay events from short-lived iodines will occur closer to thyroid cells than
      events resulting from iodine-131.

PMID- 11441946
TI  - The perinatal thyroid in iodine deficient regions: risks of radioiodines--hazards
      of stable iodine overload. A study in the newborn rat.
AB  - Administration of large quantities of stable iodine is an effective means of
      reducing the radiation burden on the thyroid in the event of a nuclear power
      plant accident. Such administration may involve countries with low baseline
      dietary iodine intake. It is questioned whether stable iodine overload is safe,
      and in particular, what are its effects in newborn infants? Iodine-deficient
      newborn rats were submitted to a single acute administration of stable iodine
      (100 microg) on the second day of life. The effects on thyroid structure were
      studied, after 24 hr and after 7 days, using light microscopy. Compared to
      controls, the thyroids of animals submitted to stable iodine overload showed, 7
      days after treatment, signs of acute toxicity including marked desquamation of
      epithelial cells and rupture of a large number of thyroid follicles. Our findings
      in iodine deficient newborn rats suggest that stable iodine overload may have
      side effects during perinatal life. This prophylactic measure should, therefore,
      be accompanied by follow-up of thyroid function. Thyroid hormones are critical
      for brain development, during the first period of life.

PMID- 11441947
TI  - Iodine prophylaxis following nuclear accidents. Concern for the neonate?
AB  - The Professor F. Delange has a substantial experience, since the last decade, in
      implementing universal salt iodization in a lot of countries, and assessing its
      impact on iodine deficiency disorders. He comments here the published results of
      D.E. Hindie et al. concerning the side effects of stable iodine overload on
      thyroid structure in the young rat (N. Colas-Linhart).

PMID- 11441948
TI  - Analytical microscopy observations of rat enterocytes after oral administration
      of soluble salts of lanthanides, actinides and elements of group III-A of the
      periodic chart.
AB  - The behavior in the intestinal barrier of nine elements (three of the group III
      A, four lanthanides and two actinides), absorbed as soluble salts, has been
      studied by two microanalytical methods: electron probe X-ray micro analysis
      (EPMA) and secondary ion mass spectrometry (SIMS). It has been shown that the
      three elements of group III-A, aluminium, gallium and indium; and the four
      lanthanides, lanthanum, cerium, europium and thulium, are selectively
      concentrated and precipitated as non-soluble form in enterocytes of proximal part
      of the intestinal tract. SIMS microscopy has shown that these elements are
      concentrated as a number of submicroscopic precipitates, most of them localized
      in the apical part of the duodenum enterocytes, where they are observed from one
      hour to 48 hr after a single intragastric administration. No precipitate is
      observed after three days. It is suggested that this mechanism of local
      concentration limits the diffusion of these elements through the digestive
      barrier, some of them being toxic and none of them having a recognized
      physiological role. Additionally, the precipitation in duodenal enterocytes, the
      life time of which is on the order of 2-3 days, allows the elements absorbed as
      soluble form to be eliminated as a non-soluble form in the digestive lumen along
      with the desquamation of the apoptotic enterocytes. The intracytoplasmic
      localization of the precipitates are supposed to be the lysosomes although no
      direct evidence could be given here due to the very small sizes of the lysosomes
      of enterocytes. The same results were not observed with the two studied
      actinides. After administration of thorium, only some very sparse
      microprecipitates could be observed in intestinal mucosa and, after
      administration of uranium, no precipitates were observed with the exception of
      some in the conjunctive part of the duodenal villi.

PMID- 11441949
TI  - The example of gastrointestinal damage induced by ionising radiation: are there
      accessible markers?
AB  - Ionising radiation exposure occurs during radiotherapy, diagnostic tests or by
      accident. In all cases the gastrointestinal tract, which is highly sensitive to
      radiation, may be at risk. Each region may respond differently to radiation
      exposure which to some extent is reflected by clinical symptoms. The evaluation
      of injury, whether acute or chronic, depends on the utilization of a variety of
      techniques. It appears that no definitive tests exist and that a multiparametric
      analysis should be undertaken. This review addresses the question of accessible
      markers associated with radiation-induced intestinal pathologies. Several
      approaches are discussed which include clinical observations, measurement of
      faecal parameters, changes in inflammatory mediators and possible applications of
      imaging techniques.

PMID- 11441950
TI  - Tissular distributions and kinetics of two renal 99mTc-radiopharmaceuticals in
      rat.
AB  - A digital radioimager (RI), conventional radioautography (RA), and tracks
      microradioautography (MRA) were used to assess the biodistributions and kinetics
      of 99mTc-dimercaptosuccinic (99mTc-DMSA) and 99mTc-mercaptoacetyltriglycine
      (99mTc-MAG3) in rat at both macroscopic and microscopic levels. Three groups of
      male Wistar rats were studied. Using gamma-counting, kidney, liver, spleen and
      blood kinetics of both tracers were assessed in the three groups. Using RA and
      RI, renal slices were analyzed in group 1 the animals being sacrified from 2 to
      60 min after injection of 99mTc-MAG3, and in group 2 the animals being sacrificed
      from 0.5 to 24 hr after injection of 99mTc-DMSA. Using MRA, renal slices were
      analyzed for 99mTc-DMSA (group 3). RA films and RI images displayed the variation
      with time of the cortical and medullary uptakes of the tracers. No regional
      heterogeneity within the different structures could be seen neither with RA films
      nor with MRA. The remaining activity in the blood 24 hr after injection of 99mTc
      DMSA was evaluated. The tissular distributions of both tracer being homogenous,
      mean values of cortical uptake seems to be acceptable for dosimetric studies. Our
      results incite to use of 99mTc-MAG3 instead of 99mTc-DMSA when both tracers may
      be indicated.

PMID- 11441951
TI  - Advanced radionuclide detection techniques for in vitro and in vivo animal
      imaging.
AB  - This review of the different methodologies used for animal imaging with
      radioactive compounds presents the most recent approaches developed for both in
      vitro and in vivo studies. The choice of a detector for analysis of the spatial
      distribution of radionuclides deposited in biological tissues results in a trade
      off between the size and nature of the region to study (in vitro or in vivo), the
      required spatial resolution and the penetrating characteristics of the ionizing
      radiation. Real time detectors are now available for quantitative imaging of 2D
      or 3D radioactive samples and offer either an increased dynamic range or a
      lowered sensitivity in comparison with film radioautography. For high resolution
      imaging, two specific techniques are proposed for applications to rodents. The
      usefulness of self-triggering intensified charge coupled device (STIC) is
      illustrated for in vitro localization in radiotoxicological studies of alpha
      emitters. For in vivo techniques, the performance of positron emission tomography
      (PET) is discussed, as a promising method of molecular imaging of biological
      processes.

PMID- 11441952
TI  - Total body 4.5 Gy gamma irradiation-induced early delayed learning and memory
      dysfunction in the rat.
AB  - In an attempt to determine the consequences of total body radiation damage on
      learning and memory in the rat, twenty-eight male Wistar rats aged 4 months
      received 4.5 Gy total body gamma-irradiation (TBI) while 28 rats received sham
      irradiation. Sequential behavioral studies of negative reinforcement including a/
      one- and b/ two-way avoidance tasks were undertaken. a/ One-way avoidance test:
      this test was performed before and after TBI. Prior to irradiation both groups
      were similar. At 20 days (D) and at 3 months post-TBI, irradiated rats had a
      significantly lower percentage of avoidance than controls but no statistical
      difference was found at 5 months post-TBI. b/ Two-way avoidance test: this test
      was performed only after TBI. At days 21, 22, 23, 24, (leaming) and at 4 or 6
      months (recalls) post-TBI the mean percentage of avoidance was significantly
      lower in irradiated than in control rats. This study demonstrates that total-body
      exposure to 4.5 Gy gamma-irradiation induces behavioral dysfunction affecting
      learning and transitorily memory. These results suggest that a relatively low
      dose of total body irradiation can induce neurological complications, which
      persist 4-6 months later.

PMID- 11441953
TI  - Low dose of the gamma acute radiation syndrome (1.5 Gy) does not significantly
      alter either cognitive behavior or dopaminergic and serotoninergic metabolism.
AB  - The aim of this study was to evaluate the early-delayed effects of a low dose of
      the gamma acute radiation syndrome (1.5 Gy) on memory and on dopaminergic and
      serotoninergic metabolism in Swiss albino CD1 mice, of various ages (6, 10 and 20
      weeks). At different times after irradiation (from 24 hr to three months), the
      mice were trained in a single-trial passive avoidance task and tested for
      retention either 24 hr or 5 days later. Their performance was compared to that of
      mice that were sham-irradiated. At the end of the behavioral test (days 3, 9, 30
      and 93), the concentrations of dopamine (DA) and serotonin (5HT) and their
      metabolites were determined in hippocampus, anterior cortex and striatum of mice
      irradiated at the age of six weeks. No significant behavioral effect was observed
      whichever the age of the animals or the delay of observation. On the contrary at
      the moderate dose of 4.5 Gy we observed a significant memory deficit 9 days after
      the exposure. Considering the neurochemical study, in the striatum or in the
      frontal cortex, no significant modification was observed whichever the delay or
      the molecule. In the hippocampus slight modifications were noted: an increase
      (+144%, p = 0.002) in DA level on day 3 after exposure, and a decrease (-27%, p =
      0.028) of 5HT level on day 30 post-irradiation. These modifications were only
      transient and not associated to modifications of the catabolites. This study
      demonstrates that total-body exposure to gamma radiation at low dose seems to
      induce only slight effects on the central nervous system.

PMID- 11441954
TI  - Could 99mTc-MIBI be used to visualize the apoptotic MCF7 human breast cancer
      cells?
AB  - Defects in key components of apoptotic pathways provide a survival advantage to
      cells and have been implicated as important factors in tumorogenesis. As
      therapeutic drug-induced apoptosis is a key component in treatment of most
      cancers, alterations in apoptotic pathways may be critical to drug resistance.
      The question is: would it be possible to distinguish apoptotic cells and
      resistant cells with a same radiotracer? In this study, we investigated the
      ability of sodium phenylacetate (NaPa), a natural cytostatic proapoptotic
      metabolite, to induce apoptosis in MCF7 human breast cancer cells. Then, we
      tested the 99mTc-MIBI accumulation in these apoptotic cells. Annexin V-FITC was
      used to identify apoptotic cells by flow cytometry. Ours results demonstrated
      that a 72 hr treatment of MCF7 cells with 40 mM NaPa induced apoptosis in 60% of
      cells. In a parallel way, 99mTc-MIBI accumulation in NaPa treated cells decreased
      for concentrations higher than 20 mM NaPa. Thus, 99mTc-MIBI accumulation
      decreased correlatively with the increasing percentage of apoptotic cells
      obtained by treatment of MCF7 cells with NaPa. These data demonstrate that NaPa
      induced apoptosis in MCF7 cells and that 99mTc-MIBI is a negative tracer of
      apoptosis: the more MCF7 cells were engaged in the apoptotic pathway, the more
      99mTc-MIBI accumulation decreased in these MCF7 apoptotic cells.

PMID- 11441955
TI  - Radiation responses in plasma membrane. Review of the present state and future
      trends.
AB  - Over the last several decades, the membrane system of the cell has been shown to
      be a fairly sensitive target for ionizing radiation. As the complex features of
      membrane functions and structure are revealed more and more, the interest of
      radiation biology grows. The present review of the biological aspects of ionizing
      radiation exposure suggests the importance of cell-to-cell contacts through
      junctions, and the signaling mechanism through receptors.

PMID- 11441956
TI  - Response of avian embryonic brain to spatially segmented x-ray microbeams.
AB  - Duck embryo was studied as a model for assessing the effects of microbeam
      radiation therapy (MRT) on the human infant brain. Because of the high risk of
      radiation-induced disruption of the developmental process in the immature brain,
      conventional wide-beam radiotherapy of brain tumors is seldom carried out in
      infants under the age of three. Other types of treatment for pediatric brain
      tumors are frequently ineffective. Recent findings from studies in Grenoble on
      the brain of suckling rats indicate that MRT could be of benefit for the
      treatment of early childhood tumors. In our studies, duck embryos were irradiated
      at 3-4 days prior to hatching. Irradiation was carried out using a single
      exposure of synchrotron-generated X-rays, either in the form of parallel
      microplanar beams (microbeams), or as non-segmented broad beam. The individual
      microplanar beams had a width of 27 microm and height of 11 mm, and a center-to
      center spacing of 100 microm. Doses to the exposed areas of embryo brain were 40,
      80, 160 and 450 Gy (in-slice dose) for the microbeam, and 6, 12 and 18 Gy for the
      broad beam. The biological end point employed in the study was ataxia. This
      neurological symptom of radiation damage to the brain developed within 75 days of
      hatching. Histopathological analysis of brain tissue did not reveal any radiation
      induced lesions for microbeam doses of 40-160 Gy (in-slice), although some
      incidences of ataxia were observed in that dose group. However, severe brain
      lesions did occur in animals in the 450 Gy microbeam dose groups, and mild
      lesions in the 18 Gy broad beam dose group. These results indicate that embryonic
      duck brain has an appreciably higher tolerance to the microbeam modality, as
      compared to the broad beam modality. When the microbeam dose was normalized to
      the full volume of the irradiated tissue. i.e., the dose averaged over microbeams
      and the space between the microbeams, brain tolerance was estimated to be about
      three times higher to microbeam irradiation as compared with broad beam
      irradiation.

PMID- 11441957
TI  - Early ultrastructural injuries in the thyroid of the normal rat radioinduced by
      diagnostic and/or therapeutic amounts of iodine-131.
AB  - After irradiation, two principal mechanisms of cytolytic cell death can be
      involved: apoptosis and necrosis. By using morphological criteria, cells
      undergoing apoptosis can be distinguished from cells dying by necrosis. In
      nuclear medicine 131I is used to ablate thyroid remnants or to treat well
      differentiated thyroid carcinoma. The aim of study was to describe the
      progressive morphological thyroid changes induced by a diagnostic and/or
      therapeutic amounts of 131I in the rat using electron microscopy, in an attempt
      to determine which is the cell death pathway and to analyse "stunned" thyroid
      tissue to elucidate this effect. Tissular and ultrastructural examinations show
      that damages induced by 131I irradiation of the normal thyroid gland are
      heterogeneous. Thyroid cells die by necrosis after this metabolic irradiation,
      and no signs of apoptosis were observed by electron microscopy. In the other
      hand, stunning effect did not seem to impair the effectiveness of 131I treatment.

PMID- 11441958
TI  - SIMS ion microscopy in cancer research: single cell isotopic imaging for chemical
      composition, cytotoxicity and cell cycle recognition.
AB  - A secondary ion mass spectrometry (SIMS) based isotopic imaging technique was
      used for studies of i/ total calcium stored in cancerous and normal cell lines
      and ii/ intracellular chemical composition (total K, Na, and Ca) in relation to
      DNA staining patterns in taxol-treated breast cancer cells. A Cameca IMS-3f ion
      microscope with 0.5 microm spatial resolution was used. Observations were made on
      frozen freeze-dried cells. In MCF-10A non-tumorigenic breast epithelial cells,
      the nucleus contained 0.6 +/- 0.10 mM and the cytoplasm 1.1 +/- 0.30 mM total
      calcium per unit volume (mean +/- S.D.). MCF-7 tumorigenic breast epithelial
      cells revealed an abnormal total calcium distribution. Their nuclei and cytoplasm
      were not significantly different in stored calcium concentrations (0.5 +/- 0.08
      mM total calcium in the nucleus and 0.6 +/- 0.07 mM in the cytoplasm).
      Furthermore, in MCF-7 cells the cytoplasmic total calcium is significantly less
      than in MCF-10A cells. Both cell lines contained approximately 150 mM
      intracellular potassium and 13 mM sodium. As 80% of the cytoplasmic total calcium
      pool in MCF-10A cells could be released with thapsigargin, it is plausible that
      the calcium storage capacity of the endoplasmic reticulum in tumorigenic MCF-7
      cells is compromised. Correlative SIMS and confocal laser scanning microscopy
      (CLSM) revealed an increase in intracellular sodium and a redistribution of
      calcium in taxol-arrested M-phase cells prior to any noticeable DNA
      fragmentation. This novel correlative approach opens new avenues of research for
      understanding intracellular ionic composition in relation to therapeutic
      cytotoxicity. Other valuable features of SIMS for cancer research shown in this
      study include subcellular imaging of calcium influx using 44Ca, 127I from
      iododeoxyuridine for S-phase recognition, and 19F from fluorinated deoxyglucose.

PMID- 11441959
TI  - SIMS evidence that carbimazole enhances spatial heterogeneity of thyroid iodine
      storage and targeting in a woman with Graves' disease.
AB  - Antithyroid drugs (ATD) are known to reduce 131I efficacy in thyrotoxicosis,
      though the underlying mechanism remains misunderstood. To study the impact of
      long term administration of carbimazole on both iodine stores (127I, secondary
      ion mass spectrometry microscopy) and targeting (125I, radioautography) at the
      intraglandular level in a woman who underwent surgery for Graves' disease. 125I
      distribution was dramatically heterogenous and large areas of the sample appeared
      poorly or no stained at all. This may correspond to flat follicles,
      hypofunctioning or ATD blocked ones and to the various histological changes
      related to the thyroiditis. SIMS counting showed huge variations of the
      interfollicular iodine stores (0 to 1.18 microg/mg) and lower mean values than
      those observed in nodular goiters. SIMS imaging depicted iodine free areas and
      others with preserved thyroglobulin synthesis, as assessed via 32S- mapping, but
      low to undetectable 127I, suggesting focal organification defects. Since ATD
      reduce iodine storage and uptake capabilities and enhance the iodine
      heterogeneity of interfollicular targeting, a related enhancement of the spatial
      131I dose distribution is unavoidable. ATD may reduce 131I efficacy by variably
      reducing the number of follicles which can be actually or significantly targeted,
      e.g. irradiated (antirecruitement effect).

PMID- 11441960
TI  - Distribution of I-BZA (N-2-diethylaminoethyl-4-iodobenzamide) in grafted melanoma
      and normal skin: a study by secondary ion mass spectroscopy.
AB  - Iodobenzamides labelled with radioactive iodine are undergoing clinical
      evaluation as imaging and potential therapeutic agents in malignant melanomas.
      However, the uptake mechanism in melanic tissues remains controversial. Using
      secondary ion mass spectrometry (SIMS), we studied the microscopic distribution
      of N-(2 diethylaminoethyl)-4 iodobenzamide (I-BZA) in B16 murine melanoma
      inoculated to C57BL/6J1 Co mice as well as in normal pigmented skin. SIMS
      provides specific detection of iodine-127 atoms entering 127I-BZA composition. In
      B16 melanoma, 127I-BZA distribution was found to be heterogeneous, with focal
      areas of high concentration corresponding to cells rich in melanin pigments. In
      skin, SIMS analysis showed 127I-BZA distribution appearing as multiple small
      selective concentration areas within the epidermis. The number of these foci
      decreased from the stratum basale towards the stratum corneum. In both tissues,
      the intracellular location appeared specifically intracytoplasmic, with no
      apparent nuclear uptake. Distribution of this molecule mirrored that of melanin
      pigments. There was no enhancement of uptake at the membrane site. These results
      suggest that, in melanic tumors as well as in normal pigmented tissue, specific
      uptake of 127I-BZA occurs in pigment cells, with a possible link to melanin
      pigments.

PMID- 11441961
TI  - Modeling radiation dose and effects from internal emitters in nuclear medicine:
      from the whole body to individual cells.
AB  - In nuclear medicine, proper application of radiation protection principles
      depends on balancing the potential risks of exposure to ionizing radiation
      against its possible benefits. Average doses to organs, in diagnostic or
      therapeutic applications, are not always representative of the doses received at
      the tissue or cellular level. Therefore, understanding of the relationship
      between the overall biological effect and absorbed dose delivered by the
      radiopharmaceutical may require study of doses at the organ, tissue, or cell
      level. In this paper, we review current models for radiation dose assessment,
      with consideration of the different models and assumptions employed for study at
      all levels of investigation.

PMID- 11441962
TI  - In vitro irradiation of blood with 99mTc: evaluation of dose and chromosome
      aberrations in irradiated lymphocytes.
AB  - The use of ionizing radiation for diagnostic or therapeutic purposes in medicine
      represents the principal source of artificial radiation to humans. Calculation of
      radiation dose is essential to the analysis of risks (biological effects) and
      benefits in any application, including nuclear medicine. The dose assessment in
      many cases is not necessarily straightforward. Many radiopharmaceuticals are
      labelled with radionuclides that undergo not only gamma-emission but also
      emission of Auger and internal conversion electrons. A typical example is
      technetium-99m (99mTc), which is used in more than 80% of nuclear medicine
      applications. In this work, in vitro studies have been carried out to evaluate
      the dose delivered to lymphocytes by human serum albumin microspheres (HSAM)
      labelled with 99mTc. Experiments were performed in order to score unstable
      chromosomal aberrations induced by 99mTc-HSAM, using conventional cytogenetic
      techniques. Henceforth, the relationship between activities introduced into blood
      samples and induced chromosomal aberrations were evaluated. To assess the dose
      absorbed in lymphocytes, electron and photon transport was performed in a simple
      model representing the system used for irradiating the cells using the MCNP Monte
      Carlo code. In this report, analysis of dose-effect curve demonstrates a linear
      quadratic response for unstable chromosome aberrations.

PMID- 11441963
TI  - Lymphocyte chromosomal aberrations and their complexity induced in vitro by
      plutonium-239 alpha-particles and detected by FISH.
AB  - G0 human lymphocytes were exposed in vitro to plutonium-239 alpha-particles, with
      doses ranging from 0 to 1.62 Gy, to provide a dose response curve and to compare
      complex rearrangements produced by high LET radiation with low LET data from
      previous work. Metaphase chromosomes 1 and 2 were painted using fluorescence in
      situ hybridization (FISH) whole chromosome probes. All unstable and stable
      aberrations involving the painted chromosomes were scored. The whole genome
      corrected alpha-coefficient for dicentrics was 0.244 +/- 0.023 and for total
      translocations 0.346 +/- 0.032, when considering simple and complex exchanges.
      The ratio of bicoloured total translocations to bicoloured dicentrics was 1.21 +/
      0.15 and the ratio of 2-way to 1-way translocations was 1.73 +/- 0.27 for
      apparently simple exchanges only. A correlation was noted between the
      distributions of dicentrics and translocations and this applied even when the
      complex rearrangements were removed. 20% of the observed rearrangements were
      complex and this observation was independent of dose. Qualitatively, following
      irradiation with alpha-particles the complex rearrangements observed were of a
      greater complexity than seen after X- or gamma-rays. Using the Savage and Simpson
      system to classify the complex rearrangements, the higher order complexes were
      found to be the most common type observed. However the insertion type increased
      while the 2F + 2G types decreased when complex rearrangements induced by alpha
      particles were compared to those formed after X- or gamma-irradiation.

PMID- 11441964
TI  - The cytogenetic dosimetry of recent accidental overexposure.
AB  - When accidental exposure to ionizing radiations is suspected, optimal choice of a
      treatment strategy requires, in addition to information about the clinical signs
      and physical dosimetry, a determination by biological parameters of the dose
      received. The scoring of unstable chromosomal aberrations in peripheral blood
      lymphocytes is the current reference method. Preparation of these samples depends
      on the goal sought--an exact assessment of several irradiations or rapid triage
      in the case of a large-scale accident. Moreover, some adaptation may be necessary
      if the irradiation is either heterogenous or not recent. Despite the robustness
      and adaptability of this procedure, conventional cytogenetics remains a tedious
      and time-consuming technique, and it requires specialized staff. Scoring
      micronuclei in binucleated lymphocytes may be an easier, simpler altemative to a
      dicentric assay. This paper, which is based on the experience acquired by the
      IPSN in recent years in expert assessment of suspected radiations, has as its
      goal to provide a succinct technical guideline of these different approaches, as
      they are adapted to suspected recent irradiation and triage.

PMID- 11441965
TI  - The sievert: an enigmatic unit.
AB  - The concept of effective dose with its unit, the sievert, is frequently
      misunderstood. Originally conceived to simplify radiation protection management,
      this concept is also proposed for another and very ambitions objective: a
      quantitative evaluation of the risks of radio-induced diseases, whatever the
      dose, the dose rate, the nature of radiation.... However, using the sievert for
      the prediction of risks of cancer or hereditary diseases is hazardous, and errors
      of prediction have been observed these last decades, for example the lack of
      prediction of the number of thyroid cancer in the very young children after the
      Chernobyl accident, and the overestimation of the risks such as leukaemia, other
      cancer and hereditary diseases. What are one sievert and its subunits?

PMID- 11441966
TI  - Structure and sequence conservation of a putative hypoxia response element in the
      lactate dehydrogenase-B gene of Fundulus.
AB  - Many aquatic habitats are characterized by periodic or sustained episodes of low
      oxygen concentration, or hypoxia, and organisms that survive in these habitats do
      so by utilizing a suite of behavioral, physiological and biochemical adjustments
      to low oxygen (1-3). In the killifish Fundulus heteroclitus, one response to
      prolonged exposure to hypoxia is an increase in the activity of lactate
      dehydrogenase-B (LDH-B), the terminal enzyme of anaerobic glycolysis, in liver
      tissue (4). An increase in glycolytic enzyme activity also occurs in mammalian
      cells during hypoxia, a process due, in part, to increased rates of gene
      transcription mediated by the hypoxia-inducible transcription factor, HIF-1 (5).
      Given that a homolog of HIF-1 has been identified in fish (6), we hypothesized
      that HIF might be involved in the observed up-regulation of LDH-B in F.
      heteroclitus. Herein, we describe the presence of DNA elements in intron 2 of the
      Ldh-B gene from F. heteroclitus that resemble hypoxia response elements (HRE)
      describedfor mammalian genes (7-10). Specifically, over a region of approximately
      50 base pairs we identified two consensus HIF-1 binding sites, as well as DNA
      elements that may bind other transcription factors (e.g., cyclic AMP response
      elements; CRE). We found that these sites were perfectly conserved among
      geographically diverse populations of F. heteroclitus, as well as being highly
      conserved among multiple species in the genus Fundulus. The spacing, orientation,
      and sequence conservation of these putative regulatory elements suggest that they
      may be functionally involved in the hypoxic regulation of Ldh-B in these fish.

PMID- 11441967
TI  - Neuronal form in the central nervous system of the tadpole larva of the ascidian
      Ciona intestinalis.
AB  - The dorsal tubular central nervous system (CNS) of the ascidian tadpole larva is
      a diagnostic feature by which the chordate affinities of this group, as a whole,
      are recognized. We have used two methods to identify larval neurons of Ciona
      intestinalis. The first is serial electron microscopy (EM), as part of a
      dedicated study of the visceral ganglion (1), and the second is the transient
      transfection of neural plate progeny with green fluorescent protein (GFP) (2), to
      visualize the soma and its neurites of individual neurons in whole-mounted larvae
      of C. intestinalis. Our observations reveal that ascidian larval neurons are
      simple inform, with a single axonal neurite arising from a soma that is either
      monopolar or has only very few, relatively simple neurites arising from it, as
      part of a presumed dendritic arbor. Somata in the visceral ganglion giving rise
      to axons descending in the caudal nerve cord are presumed to be those of motor
      neurons.

PMID- 11441968
TI  - Larval muscle contraction fails to produce torsion in a trochoidean gastropod.
AB  - The causes and effects of ontogenetic torsion in gastropods have been debated
      intensely for more than a century (1-19). Occurring rapidly and very early in
      development, torsion figures prominently in shaping both the larval and adult
      body plans. We show that mechanical explanations of the ontogenetic event that
      invoke contraction of larval retractor muscles are inadequate to explain the
      observed consequences in some gastropods. The classic mechanical explanation of
      Crofts (4, 5) and subsequent refinements of her explanation have been based on
      species with rigid larval shell properties (18, 19) that cannot be extrapolated
      to all gastropods. We present visual evidence of the lack of rigidity of the
      uncalcified larval shell in a basal trochid gastropod, Margarites pupillus
      (Gould), and provide photographic confirmation of our prediction that larval
      retractor muscle contraction is insufficient to produce more than local
      deformation or dimpling at the site of muscle insertion. These findings do not
      refute muscular contraction as a primary cause of ontogenetic torsion in
      gastropods that calcify their larval shells prior to the onset of torsion, nor do
      they refute the monophyly of torsion. They do, however, suggest that torsion may
      be a loosely constrained developmental process with multiple pathways to the more
      constrained end result (20, 21).

PMID- 11441969
TI  - Multiple paternity in Littorina obtusata (Gastropoda, Littorinidae) revealed by
      microsatellite analyses.
AB  - Parental identity for juvenile Littorina obtusata was determined from three egg
      masses by means of microsatellite DNA markers. Results confirm that the attendant
      adult female in each case was the dam of the offspring and that at least 4-6
      males contributed to each brood. This correlates with our behavioral observations
      that indicated multiple copulations between the female and several males in each
      experimental aquarium. A significant number of offspring from each brood were
      sired by non-sampled males (males that had copulated with females before capture)
      whose sperm had been stored by the female. This is the first direct evidence of
      multiple paternity in the Littorinidae. Results are discussed in reference to
      current theories of sperm competition, male precedence, and cryptic female
      choice.

PMID- 11441970
TI  - Development of serotonin-like and SALMFamide-like immunoreactivity in the nervous
      system of the sea urchin Psammechinus miliaris.
AB  - The present immunocytochemical study utilizes serotonin and SALMFamide antisera,
      together with confocal laser scanning microscopy, to provide new information
      about the development of the nervous system in the sea urchin Psammechinus
      miliaris (Echinodermata: Echinoidea). Special attention is paid to the extent of
      the nervous system in later larval stages (6-armed pluteus to metamorphic
      competency), a characteristic that has not been well described in this and other
      species of sea urchin. An extensive apical ganglion appears by the 6-armed
      pluteus stage, forming a complex of 10-20 cells and fibers, including discrete
      populations of both serotonin-like and SALMF-amide-like immunoreactive cells. At
      metamorphosis this complex is large, comprising at least 40 cells in distinct
      arrays. Serotonin-like immunoreactivity is also particularly apparent in the
      lower lip ganglion of 6- to 8-armed plutei; this ganglion consists of 15-18 cells
      that are distributed around the mouth. The ciliary nerves that lie beneath the
      ciliary bands in the larval arms, the esophagus, and a hitherto undescribed
      network associated with the pylorus all show SALMFamide-like immunoreactivity.
      The network of cells and fibers in the pyloric area develops later in larval
      life. It first appears as one cell body and fiber, then increases in size and
      complexity through the 8-armed pluteus stage to form a complex of cells that
      encircles the pylorus. SALMFamide-like, but not serotonin-like, immunoreactivity
      is seen in the vestibule wall, tube feet, and developing radial nerve fibers of
      the sea urchin adult rudiment as the larva gains metamorphic competency.

PMID- 11441971
TI  - Function and functional groupings of the complex mouth apparatus of the squat
      lobsters Munida sarsi Huus and M. tenuimana G.O. Sars (Crustacea: Decapoda).
AB  - Like all other decapods, the anomuran squat lobsters Munida sarsi and M.
      tenuimana have a mouth apparatus composed of six pairs of mouthparts plus labrum
      and paragnaths (upper and lower lips). To study the functional significance of
      this complexity, we examined the mouthparts with scanning electron microscopy and
      also observed their function directly, under laboratory conditions, using macro
      video equipment. No differences were found between the two species. The movement
      patterns of the mouthparts are described in detail and illustrated as serial
      drawings. Proceeding from maxillipeds 3 towards the mandibles, the movement
      pattern gets increasingly stereotypical, with the mandibles performing but a
      single movement in a medio-lateral plane. From morphology, the mouthparts are
      subdivided into 20 parts, but from the functional analyses the 20 parts form 8
      functional groups: 1, transporting mouthparts (maxilliped 2 endopod and
      maxilliped 3 endopod); 2, transporting-aligning mouthparts (maxilliped 1 basis);
      3, sorting-aligning mouthparts (maxilla 1 basis and maxilla 2 basis); 4, current
      generating mouthparts (flagella of maxilliped 2 and maxilliped 3 exopods); 5,
      cutting-crushing mouthparts (incisor and molar processes, labium, and mandibular
      palp); 6, ingesting mouthparts (maxilla 1 coxa, maxilla 2 coxa, and maxilliped 1
      coxa); 7, respiratory mouthparts (scaphognathite, maxilliped 1 epipod, and
      maxilliped 2 and maxilliped 3 exopods); and 8, dorso-ventral mouthparts (maxilla
      1 endopod, maxilla 2 endopod, maxilliped 1 endopod, and maxilliped 1 exopod).
      These groupings apply mostly to the processes of food handling and have little
      significance with respect to grooming. When comparing our results to the
      literature on other decapods, we found much resemblance to conditions in other
      anomurans.

PMID- 11441972
TI  - Phylogeny of hydrothermal-vent-endemic gastropods Alviniconcha spp. from the
      western Pacific revealed by mitochondrial DNA sequences.
AB  - Mitochondrial genes for cytochrome oxidase I (COI) from hydrothermal-vent-endemic
      gastropods of the genus Alviniconcha were sequenced to determine the phylogenetic
      relationships among specimens from three areas in the western Pacific.
      Individuals of Alviniconcha hessleri were collected at two vent fields (depths
      1470 m and 3600 m) in the Mariana Trough. Specimens collected in the North Fiji
      Basin could be divided into two genetically distinct groups, both of which also
      differed from A. hessleri from the Mariana Trough. None of the specimens of the
      genus Alviniconcha collected in the Manus Basin differed genetically from the
      dominant group from the North Fiji Basin. We suggest that the specimens of the
      genus Alviniconcha analyzed in the present study can be tentatively classified
      into A. hessleri and two undescribed species.

PMID- 11441973
TI  - Ecology and behavior of Gecarcoidea natalis, the Christmas Island red crab,
      during the annual breeding migration.
AB  - The terrestrial crab Gecarcoidea natalis is endemic to the forests of Christmas
      Island but must migrate each year to the coast to breed. During 1993 and 1995,
      radio-tracking, mark and recapture, and counting methods were used to establish
      the routes, walking speeds, direction of travel, and destinations of migrating
      crabs, as well as crab numbers and distribution. The density of crabs ranged from
      0.09 to 0.57 crabs per square meter, which gave a population estimate of 43.7
      million adult crabs on the island. During the dry season the crabs were
      relatively inactive but on arrival of the wet season immediately began their
      migration. The crabs generally walked in straight lines, and most crabs from
      around the Island traveled toward the northwest shore instead of simply walking
      toward the nearest shore. The maximum recorded distance walked by a red crab in
      one day was 1460 m, but the mean was 680 m per day in 1993 and 330 m in 1995.
      Comparing the 1993 and 1995 study seasons, there was a 3-week difference in the
      timing of the start of the migration, but the spawning date was fixed by the
      lunar phase and took place 17 to 18 days after mating. In 1993, late rain
      prompted a "rushed" migration and crabs walked directly to their shore
      destinations; in contrast, in 1995 most crabs made stops of 1 to 7 days during
      the downward migration. By giving the crabs a chance to feed along the way and
      minimizing the time that the population was concentrated near the shore, these
      stops may be important in ensuring that the animals have enough food after the
      long dry season. Furthermore, this behavior implies that the crabs are able to
      judge how far away they are from the shore during the migration.

PMID- 11441974
TI  - Metabolic status and respiratory physiology of Gecarcoidea natalis, the Christmas
      Island red crab, during the annual breeding migration.
AB  - With the arrival of the monsoonal rains and after months of inactivity during the
      dry season, the terrestrial crab Gecarcoidea natalis embarks on its annual
      breeding migration to the coast. The physiological demands of the migration were
      assessed by determining respiratory gases in the hemolymph, key metabolites, and
      energy stores in G. natalis during two migratory seasons. At the end of each day
      of migration the pulmonary hemolymph PO2 decreased by 1-2.5 kPa, but the
      hemocyanin remained saturated with O2 and the venous reserve was largely
      unchanged (O2 > 0.4 mmol x l(-1)). The breeding migration of red crabs was
      accomplished without recourse to anaerobiosis, even though at times walking
      speeds (up to 6.2 +/- 0.5 m x min(-1)) exceeded those that promoted anaerobiosis
      in non-migrating crabs and in crabs exercised in the laboratory. In contrast to
      all previous studies, at the end of each day of migrating, red crabs experienced
      an alkalosis (up to 0.1 pH units) rather than any acidosis. This alkalosis was
      removed overnight when the crabs were inactive. Although there were seasonal
      fluctuations in the glycogen, glucose, and triglyceride stores, crabs engaging in
      the migration did not draw on these stores and must have fed along the way. In
      contrast, crabs returning from breeding activities on the shore terraces had
      significantly depleted glycogen stores. Additionally, in 1993, the male crabs
      returning from the breeding activities on the terraces were dehydrated and
      experienced a decrease in muscle tissue water of 11%. In contrast to the breeding
      migration per se, fighting for burrows in which breeding occurs produced severe
      anaerobiosis in males, especially the victors: after 135 s of combat, the maximum
      L-lactate concentration in the hemolymph was 35 mmol x l(-1). It appears that
      burrowing, courtship, and mating are more demanding than the migration itself.
      Furthermore, the data provide evidence that the metabolic responses of migrating
      individuals of G. natalis might be different from those at other times of the
      year.

PMID- 11441975
TI  - Morphology of the symbiosis between Corculum cardissa (Mollusca: Bivalvia) and
      Symbiodinium corculorum (Dinophyceae).
AB  - Light and transmission electron microscopy of tissues of the symbiotic clam
      Corculum cardissa (L) showed that a symbiotic dinoflagellate, Symbiodinium
      corculorum (Trench), is found predominantly in the mantle and the gills. The data
      suggest that in C. cardissa the algae are located in a zooxanthellal tubular
      system that is associated with the hemocoel and is similar to that seen in
      tridacnine ("giant") clams. The algae occur within the lumen of the tertiary
      tubules and are thus separated from the hemolymph by a tissue that is one cell
      layer thick. Under a light microscope the tertiary tubules appear as rows of
      symbionts originating from the digestive diverticulum, presumably branching from
      the primary tubules that are also seen in symbiotic tridacnine clams. This
      morphological arrangement is discussed with regard to the ontogeny and the
      evolution of the tubular system within symbiotic bivalves.

PMID- 11441976
TI  - 5-Hydroxytryptamine stimulates net Ca2+ flux in the ventricular muscle of a
      mollusc (Busycon canaliculatum) during cardioexcitation.
AB  - Noninvasive, self-referencing calcium (Ca2+) electrodes were used to study the
      mechanisms by which 5-hydroxytryptamine (5-HT) affects net Ca2+ flux across the
      sarcolemma of myocytes from ventricular trabeculae (from a marine gastropod,
      Busycon canaliculatum). Treatment of isolated trabeculae with 5-HT causes a net
      Ca2+ efflux, which is 30% blocked by verapamil. These findings suggest that the
      efflux is in part the result of a previous Ca2+ influx through L-type Ca2+
      channels and is due to a rapid Ca2+ extrusion mechanism inherent to the
      sarcolemma of these myocytes. 5-HT-induced net Ca2+ efflux is also reduced by
      about 40% by treatment with a sodium (Na+)-free, lithium (Li+)-substituted
      saline, which shuts down the Na-Ca exchanger during Ca2+ extrusion. Cyclopiazonic
      acid (CPA), an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ ATPase, almost
      completely abolishes the 5-HT-induced net Ca2+ efflux, suggesting that the SR
      rather than the extracellular pool is the primary Ca2+ reservoir serving 5-HT
      induced excitation.

PMID- 11441977
TI  - Prevention of venous thromboembolism: recommendations based on the International
      Consensus and the American College of Chest Physicians Sixth Consensus Conference
      on Antithrombotic Therapy.
AB  - The primary purpose of a Consensus Conference is to provide informed guidance on
      treatment decisions, assisting clinicians to make the optimal therapeutic choice
      for the patient, and providing protection against unjustified malpractice
      actions. The First American College of Chest Physicians (ACCP) Consensus
      Conference took place in 1985 and, using a systematic approach, provided
      recommendations for anti-thrombotic therapy based on published studies, and
      graded those recommendations on the level of clinical evidence. The European
      Consensus Conference was convened in 1991 to build on this process. During this
      period, the main developments included the introduction and widespread use of new
      thromboprophylactic agents such as low-molecular-weight heparins, and improved
      risk assessment, including an awareness that outpatients and general medical
      patients may also be at risk. Subsequently, the recommendations have been
      carefully reviewed and updated by experts who represent the extensive range of
      opinions in the field. The latest International Consensus Statement was published
      in 1997, and the most recent ACCP Consensus in 2001 and they provide extensive
      practice guidelines in the management of venous thromboembolism.

PMID- 11441978
TI  - Vascular thrombohemorrhagic disorders: hereditary and acquired.
AB  - This review has summarized the more important diseases that may be accompanied by
      or lead to a disorder of hemostasis or thrombosis via alterations of the
      vasculature. It is to be stressed that the vascular component of hemostasis is
      often overlooked by clinicians caring for patients with disorders of hemostasis
      and thrombosis. It should be appreciated that the vasculature is intricately
      related to the coagulation protein system and to platelets when involved in
      thrombohemorrhagic diatheses. Although many vascular disorders may lead to
      hemorrhage or thrombosis, it must be appreciated that often it is impossible to
      discern between a primary vascular defect/damage and a defect that has been
      induced by platelet activation/dysfunction or procoagulant abnormalities.

PMID- 11441979
TI  - Anticoagulation: the present and future.
AB  - Thrombin is a central bioregulator of coagulation and is therefore a key target
      in the therapeutic prevention and treatment of thromboembolic disorders,
      including deep vein thrombosis and pulmonary embolism. The current mainstays of
      anticoagulation treatment are heparins, which are indirect thrombin inhibitors,
      and coumarins, such as warfarin, which modulate the synthesis of vitamin K
      dependent proteins. Although efficacious and widely used, heparins and coumarins
      have limitations because their pharmacokinetics and anticoagulant effects are
      unpredictable, with the risk of bleeding and other complications resulting in the
      need for close monitoring with their use. Low-molecular-weight heparins (LMWHs)
      provide a more predictable anticoagulant response, but their use is limited by
      the need for subcutaneous administration. In addition, discontinuation of heparin
      treatment can result in a thrombotic rebound due to the inability of these
      compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are
      able to target both free and clot-bound thrombin. The first to be used was
      hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and
      efegatran, have subsequently been developed, and these agents are better able to
      inhibit clot-bound thrombin and the thrombotic processes that take place at sites
      of arterial damage. Such compounds inhibit thrombin by covalently binding to it,
      but this can result in toxicity and nonspecific binding. The development of
      reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in
      safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as
      ximelagatran, are set to provide a further breakthrough in the prophylaxis and
      treatment of thrombosis.

PMID- 11441980
TI  - Plasma markers of endothelial dysfunction in chronic obstructive pulmonary
      disease.
AB  - We studied some endothelial cell activity plasma markers, nitric oxide (NO),
      thrombomodulin (TM), selectins (sP-, sE-, sL-selectin: platelet-P, endothelium-E,
      leukocyte-L), and tissue factor pathway inhibitor (TFPI) in 14 patients with
      chronic obstructive pulmonary disease (COPD), matched with 20 normal controls, to
      evaluate their endothelial cell dysfunction. Both NO (patients: 23.42 +/- 1.67
      microg/mL: controls: 40.0 +/- 3.38 microg/mL) and TM levels (patients: 5.46 +/-
      1.32 ng/mL; controls: 12.9 +/- 0.51 ng/mL) were significantly decreased in COPD
      (p < 0.001). sP-selectin levels (patients: 79.42 +/- 18.20 ng/mL, controls: 37.5
      +/- 2.84 mg/mL) were significantly higher (p < 0.02), whereas sL-selectin levels
      (patients: 584.9 +/- 78.98 ng/mL, controls: 1,054.02 +/- 61.28 ng/mL) were
      significantly decreased in patients with COPD (p < 0.001). In contrast, no
      differences were seen in sE-selectin. Patients with COPD showed a significantly
      higher (p < 0.001) TFPI antigen plasma level (mean 112.28 +/- 6 .45 ng/mL;
      controls 77.68 +/- 0.28 ng/mL) than controls. Our data support the concept of
      some form of endothelial cell dysfunction, and coagulation abnormalities are
      present in patients with COPD. However, because the endothelium seems to produce
      a defense mechanism, the potential usefulness of an antithrombotic therapy in
      these patients needs further investigation.

PMID- 11441981
TI  - Individual dosing of ASA prophylaxis by controlling platelet aggregation.
AB  - Acetylsalicylic acid is widely used in the primary and secondary prevention of
      cardiovascular diseases. In the current study, we used platelet aggregation ex
      vivo in platelet-rich plasma induced with arachidonic acid as a routine method
      for the determination of the individual dose of acetylsalicylic acid necessary to
      inhibit platelet aggregation in 108 patients with cardiovascular diseases. In 40%
      of all patients studied, a dose of 30 mg/day was sufficient to block the
      arachidonic acid-induced platelet aggregation nearly completely. In 50% of all
      patients, a dose of 100 mg/day was necessary. In 10% of all patients, the dose
      had to be further increased to 300 mg/day or even to 500 mg/day to inhibit
      platelet aggregation nearly completely. These results demonstrate that platelet
      aggregation can be used as a simple routine laboratory method to control
      acetylsalicylic acid treatment in patients with cardiovascular diseases and to
      determine individual doses of acetylsalicylic acid for a nearly complete
      inhibition of platelet aggregation. With a standard dose of 100 mg/day, 10% of
      the patients were nonresponders.

PMID- 11441982
TI  - Low tissue plasminogen activator relative to plasminogen activator inhibitor-1 as
      a marker of cardiac complication in children with Kawasaki disease.
AB  - To determine whether the fibrinolytic system is related to the occurrence of
      cardiac complication in Kawasaki disease, we measured tissue plasminogen
      activator, plasminogen activator inhibitor-1, and related factors in the plasma
      of children with Kawasaki disease. Patients (mean age, 1.8 years) were classified
      into patients with cardiac complication (n = 9) and no complication (n = 14)
      groups echocardiographically. They underwent single, high-dose, intravenous-gamma
      globulin infusion therapy. Blood was drawn just before and the day after the
      single high-dose intravenous gamma-globulin infusion therapy (acute phase), and
      at early and late convalescent phases. Leukocytosis was normalized immediately
      after the single, high-dose, intravenous gamma-globulin infusion therapy. C
      reactive protein and fibrinogen were increased in the acute phase and normalized
      by convalescent phases. D-dimer fraction of fibrin degradation products changed
      in a similar manner. Tissue plasminogen activator and plasminogen activator
      inhibitor-1 were increased in acute phase. The tissue plasminogen
      activator/plasminogen activator inhibitor-1 ratio was lower in the complication
      group than in the no complication group throughout the observation period (0.095
      versus 0.208 after single, high-dose, intravenous gamma-globulin infusion
      therapy, p = 0.006; 0.094 versus 0.183 at late convalescent phase, p = 0.024). A
      low tissue plasminogen activator/plasminogen activator inhibitor-1 ratio can
      predict the propensity for cardiac complication, and can help the physician to
      decide whether additional therapies are necessary in acute phase Kawasaki
      disease.

PMID- 11441983
TI  - Singlet oxygen inhibits agonist-induced P-selectin expression and formation of
      platelet aggregates.
AB  - Major mediators of activated polymorphonuclear leukocytes (PMN) are the oxidants
      HOCl and chloramine, which are a source for the nonradical photon-emitting
      oxidant singlet oxygen (1O2). We were interested in a possible platelet
      modulating activity of 1O2. As a stable 1O2 source we chose the mild oxidant
      chloramine T (CT), which mimics the natural chloramine N-chloro-taurine. Freshly
      drawn native whole blood from donors (n = 5) was incubated at 0 to 3 mM CT for 1
      minute at 37 degrees C. Then saline. 10 microM adenosine diphosphate (ADP), 5
      microg/mL collagen, or 6.25 microM thrombin receptor activator peptide (TRAP)
      were added and the mixtures were allowed to incubate for 3 minutes at 37 degrees
      C. Aliquots of activated blood were fixed in 1% para-formaldehyde. After removal
      of the fixative, platelets were labeled with anti-CD61-FITC and anti-CD62P-PE
      antibodies and analyzed by flow cytometry. An oxidant concentration-dependent
      decrease in the expression of P-selectin appeared (at 3 mM CT to 39, 23, and 20%
      of the 100% saline control level for ADP, collagen, and TRAP, respectively).
      There was also an oxidant concentration-dependent decrease in the formation of
      platelet aggregates (at 3 mM CT to 8, 12, and 13% of the 100% saline control
      level for ADP, collagen, and TRAP, respectively; the 50% effective dose was 1.0
      to 1.5 mM chloramine). In ADP- and TRAP-stimulated platelets, an oxidant-mediated
      increase in platelet fragments appeared (at 3 mM CT: three- to fourfold of the
      initial value). The addition to the blood of 30 mM of the oxyradical scavenger
      mannitol in contrast to excess methionine did not antagonize these oxidative
      modulations of platelet activation. The results were confirmed using equimolar
      concentrations of NaOCI and N-chloro-taurine. This study shows that 1O2 inhibits
      platelets, decreasing the expression of CD62P and the formation of platelet
      aggregates. Activated PMN might modulate hemostasis, shifting it into an
      antithrombotic state. The physiologic signal action and the direct anticoagulant
      action of 1O2 (released by chloramines such as vancomycin) might be a new
      principle for pharmacologic intervention in atherothrombosis.

PMID- 11441984
TI  - Tissue factor pathway inhibitor release induced by defibrotide and heparins.
AB  - We evaluated the release of tissue factor pathway inhibitor (TFPI) induced by
      defibrotide (DF), a single-stranded, negatively charged polydeoxyribonucleotide
      extracted from mammalian organ. Ten normal volunteers were injected with an
      intravenous bolus of 400 mg DF and 2,000 IU unfractionated heparin (UFH). In
      addition, three volunteers were also injected with an intravenous bolus of 2,000
      anti-Xa U of two low-molecular-weight heparins (LMWHs), enoxaparin and
      nadroparin. UFH caused a 4-fold increase in plasma TFPI at 5 minutes, with a
      decrease that was parallel to the heparin level measured by the anti-Xa assay.
      However, at 80 minutes, although the plasma anti-Xa activity of UFH was almost
      undetectable, the level of TFPI remained 2-fold baseline. DF induced an increase
      of TFPI that was 2-fold higher than the baseline level, with a steady state
      achieved between 5 and 20 minutes. At 40 minutes, the TFPI levels returned to
      basal level. This pattern was not coincident with the clearance of DF and at 40
      minutes, the concentration of DF was still one third of the levels at 5 minutes
      (25.4 +/- 4.04 microg/mL). Both of the LMWHs induced a similar TFPI peak level at
      5 minutes (1.5-fold increase) and at 40 minutes the TFPI levels returned to the
      initial levels. At 5 minutes, both LMWHs showed a higher plasma anti-Xa activity
      than UFH, which was detectable even at 80 minutes. The current study demonstrated
      that one of the mechanisms of the antithrombotic activity of DF is mediated via
      TFPI. Furthermore, the release of TFPI by heparin is mediated by non-antithrombin
      III binding fragments. Thus, polyanionic electrolytes are capable of releasing
      TFPI irrespective of their antithrombin III effect.

PMID- 11441985
TI  - Plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tPA/PAI-1
      complex in patients with disseminated intravascular coagulation and thrombotic
      thrombocytopenic purpura.
AB  - In this study, we examined changes in the plasma levels of total plasminogen
      activator inhibitor-I (PAI-I) and tissue-type plasminogen activator (tPA)/PAI-I
      complex in patients with disseminated intravascular coagulation (DIC) and in
      those with thrombotic thrombocytopenic purpura (TTP) to investigate the
      fibrinolytic function and its relation to organ failure. The plasma levels of
      total PAI-1 and tPA/PAI-I complex were significantly higher in patients with DIC,
      pre-DIC, and TTP than in those with non-DIC. The plasma levels of thrombin
      antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer,
      thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex were significantly higher
      in patients with organ failure than in those without organ failure. The plasma
      levels of total PAI-I and tPA/PAI-I complex were markedly increased in patients
      with acute leukemia. The plasma levels of total PAI-I, but not those of tPA/PAI-I
      complex, were significantly increased in patients with sepsis or with solid
      cancer. In all cases, total PAI-I or tPA/PAI-I complex was not significantly
      correlated with any hemostatic marker. Measurement of total PAI-I and tPA/PAI-I
      complex may be useful in the diagnosis of DIC.

PMID- 11441986
TI  - Factor V Leiden and prothrombin G20210A in relation to arterial and/or vein
      rethrombosis: two cases.
AB  - The factor V Leiden (FV Leiden) and prothrombin G20210A mutations, are the most
      common established genetic risk factors for deep vein thrombosis (DVT). However,
      the relationship between these mutations and arterial thrombotic syndromes
      (coronary heart disease, myocardial infarction, stroke) has not been established.
      Some studies have suggested a relationship between them, but other authors have
      considered it unlikely that these anomalies are a major risk factor for arterial
      thrombosis. From the clinical point of view, a question arises concerning the
      risk of repeated thrombosis in patients carrying one of these two mutations. The
      question is whether the recurrence is attributable to the mutations or to the
      presence of additional circumstantial risk factors. As the risk of repeated
      thrombosis varies considerably from one patient to another, decisions about long
      term treatment require weighing the persistence of risk factors for vascular
      disease (venous and arterial), especially in selected cases such as young
      patients or patients with thrombosis of unusual localization.

PMID- 11441987
TI  - Cerebral vein thrombosis and lupus anticoagulant antibodies.

PMID- 11441988
TI  - Alternate methods for laparoscopic management of adnexal masses greater than 10
      cm in diameter.
AB  - PURPOSE: We describe alternate laparoscopic methods for inspection and removal of
      large adnexal masses, and report our experience with 18 cases in which these
      methods were used. PATIENTS AND METHODS: Between April 1994 and January 2000, the
      first author performed operative laparoscopy on 18 patients, each of whom had at
      least one adnexal mass with maximum diameter greater than 10 cm. Mean patient age
      was 32 years (range 11 to 82). Seventeen of the 18 patients were premenopausal.
      All procedures were performed at one of two community hospitals in Seattle or at
      Yuan's General Hospital in Taiwan. Preoperative screening included pelvic exam,
      tumor markers, and ultrasound. RESULTS: One 82-year-old patient underwent planned
      laparoscopic bilateral oopherectomy. In the other 17 cases the operative goal was
      cystectomy or unilateral oopherectomy with conservation of reproductive function.
      Cystectomy was successfully performed in five of these cases (29.4%). The
      remaining 12 patients underwent either unilateral oopherectomy (10 cases, 58.8%),
      or unilateral salpingo oopherectomy (2 cases, 8.8%) due to the extent of their
      mass. Sixteen of the 18 cases in this series were successfully managed by a
      single laparoscopic surgery, one case required a second-look laparoscopy, and in
      one case a malignancy was found by histological analysis of permanent section,
      which required a second laparoscopy for staging and debulking. CONCLUSIONS: Large
      adnexal masses can be successfully managed with minimal hospital stay using
      laparoscopic techniques, when care is taken to avoid rupture and spillage of cyst
      contents, and thorough inspection of the mass and abdominal cavity is made
      possible. The probability of finding an unexpected malignancy is low. In those
      cases where a malignancy is found, appropriate cytoreductive staging surgery can
      be performed immediately.

PMID- 11441989
TI  - Liver tumors and minimally invasive surgery: a feasibility study.
AB  - Laparoscopic liver resection has not yet been established, although recent
      reports document that liver resection can be performed safely by the laparoscopic
      approach. Other interventional procedures like cryoablation have also been
      introduced in treatment of liver metastases. In this report 11 liver resections
      performed laparoscopically in eight patients are presented. Six patients had
      colorectal metastases, one a metastases from a malignant melanoma, and one
      patient had focal nodular hyperplasia. Two patients received synchronous
      cryoablation of remaining liver metastases. During follow up, two patients
      received percutaneous cryoablation of liver recurrences monitored by an open
      configuration magnetic resonance scanner. All except one of the tumors we
      attempted to remove had free resection margins (re-resection of new metastasis).
      No complications occurred except an atelectasis of the left lower pulmonary lobe
      in one patient. Median postoperative hospital stay was 3 days, and median
      postoperative opioid-dependent days was 1. The report demonstrates that minimally
      invasive techniques may safely be combined in hepatic intervention, and that the
      advantages of minimally invasive surgery, such as reduced hospital stay and less
      patient discomfort, also applies to liver resections.

PMID- 11441990
TI  - Extensive liver resection: can it be applicable to laparoscopic surgery?
AB  - Due to major technical barriers, the safety and efficacy of laparoscopic hepatic
      resection is not well established. Laparoscopic liver resection has been
      described. Wedge resections or marginal resections rather than more formal
      hepatic resections for benign diseases only have been described lately. Anatomic
      hepatic resection and nonanatomical resection were also reported. But the
      technique still needs to be standardized and applied in a large-scale population.
      During the last 20 years, there has been a trend toward direct control of hepatic
      injury by adequate debridment of nonviable hepatic tissue along nonanatomical
      lines. The trauma experience emphasized two important concepts: the search for
      the most expedient method of hemorrhage control in the nonstable trauma patient,
      and a hepatic resection that need not be based on precise anatomic planes. The
      aim of this paper is to present the data and instruments available to apply
      toward laparoscopic liver resection.

PMID- 11441991
TI  - Safety and quality assurance of endoscopic surgery.

PMID- 11441992
TI  - Problems with laparoscopic instruments: opinions of experts.
AB  - INTRODUCTION: Laparoscopic surgery is particularly known for its complex
      technique, which calls for operative analysis of laparoscopic instruments. This
      study investigates the opinion of experts about clinical problems with
      instruments occurring during laparoscopic surgery. METHODS: A questionnaire was
      used to obtain the opinions of expert laparoscopic surgeons about difficulties
      experienced operatively using laparoscopic instruments. RESULTS: The laparoscopic
      surgeons indicated that coagulators were especially prone to cause complications
      of the gastro-intestinal tract, vascular injuries, and bile duct injuries.
      Dissectors were considered to play a role in the occurrence of solid organ and
      bile duct injuries, and retractors to cause solid organ injuries. Insufficient
      functionality of the instruments and insufficient quality of the image were
      indicated to contribute to the instrument's risks. CONCLUSION: The questionnaire
      identified technological deficiencies prone to cause operative complications. The
      results provide a basis for the interaction between surgeons and engineers, and
      serve as pilot information on which to base an in-depth object evaluation of
      instrument problems.

PMID- 11441993
TI  - Closure of laparoscopic trocar site wounds with cyanoacrylate tissue glue: a
      simple technical solution.
AB  - Cyanoacrylate-based tissue glue has been widely used for many years around the
      world, and was recently approved for use in the United States, mainly for skin
      cuts and lacerations. Other applications were described, in different surgical
      situations. Although ideal for small, clean incisions, its use in laparoscopic
      surgery is currently limited. Over a year period, 100 patients with more 250
      trocar site wounds had their wounds glued using histoacryl. Infection rate was
      extremely low (one case), and partial dehiscence of the wound happened in two
      patients, where wound edge approximation was not optimal. Cosmetic results were
      excellent and patient satisfaction was high, as no sutures had to be removed.
      Glue application is easy and quick, with no risk of needle sticks, and it is a
      viable option for laparoscopic wound closure.

PMID- 11441994
TI  - Robotically assisted laparoscopic hysterectomy and adnexal surgery.
AB  - BACKGROUND: In this pilot study, we tested the feasibility and safety of using a
      robotic device to perform complex gynecologic surgery. METHODS: Ten female pigs
      underwent adnexal surgery (n = 5) or hysterectomy (n = 5) using the "Zeus"
      robotic device. The surgeon operates while sitting at the console away from the
      surgical table on which the robotic arms are fixed. Both procedures were
      performed solely with the robotic arms. After 1 week of observation the animals
      were sacrificed and the surgical site was explored. RESULTS: The procedure was
      completed successfully in all cases. No animal required conversion to laparotomy
      or nonrobotic laparoscopic assistance. The mean operative time (+/- SD) was 170
      +/- 44 min for adnexal surgery and 200 +/- 57 min for hysterectomy. No
      complications occurred. No ureteral injuries were found on necropsy. CONCLUSION:
      Although designed for laparoscopic microsuturing, this robotic technology has the
      potential to be used for more complex gynecologic procedures.

PMID- 11441995
TI  - Laparoscopic management of abdominal complications in ventriculoperitoneal shunt
      surgery.
AB  - Ventriculoperitoneal (VP) shunts are among the most frequently performed
      operations in the management of hydrocephalus. Abdominal complications, though
      rare, are reported to occur in 5-47%. VP shunt obstruction or malfunction leads
      to raised intracranial pressure, which requires immediate intervention. Recently
      we have used the laparoscope to manage abdominal complications of VP shunt in two
      patients. The first patient had hydrocephalus secondary to tubercular meningitis.
      She developed recurrent intraabdominal cerebrospinal fluid (CSF) pseudocysts,
      possibly due to subtle peritoneal infection. In the second patient, who developed
      hydrocephalus following subarachnoid haemorrhage, the lower end of the shunt was
      malfunctioning due to retraction into the extraperitoneal tissues. The distal end
      of the VP shunt was revised in both patients with the help of a laparoscopically
      assisted technique. Thus, a conventional laparotomy, along with its various
      associated postoperative problems, was avoided without compromising the quality
      of surgery.

PMID- 11441996
TI  - Omental herniation through a 3-mm umbilical trocar site: unmasking a hidden
      umbilical hernia.
AB  - BACKGROUND: The incidence of umbilical hernia following laparoscopic surgery
      varies from 0.02-3.6%. The incidence of pre-existing fascial defects, however,
      may be as high as 18% in patients undergoing abdominal laparoscopic surgery.
      Previous recommendations have been made to close any fascial defect greater than
      or equal to 10 mm. Reported here is a case of herniation through a 3-mm trocar
      site incision and the discovery of a pre-existing fascial defect. CASE REPORT: A
      32-year-old female underwent an uncomplicated laparoscopic tubal ligation using a
      3-mm umbilical port. Prior to umbilical trocar removal at the completion of the
      case, the carbon dioxide was evacuated from the abdomen and the sleeve was
      withdrawn under direct vision. Neither the fascial nor skin incisions were
      sutured. On postoperative day two, the patient returned with omentum herniating
      from the 3-mm site. At surgery, a 1.5-cm pre-existing fascial defect was
      discovered adjacent to the trocar site. The hernia sac tracked laterally to the
      base of the umbilicus, and the omentum had slid into the sac and out the skin
      opening. CONCLUSION: As this report illustrates, herniation associated with
      laparoscopic trocar sites can occur with incisions as small as 3 mm. The presence
      of pre-existing fascial defects can cause increased morbidity in any laparoscopic
      surgery, and as illustrated in this report, may predispose the patient to site
      herniation. The detection and management of these defects is crucial in
      preventing postlaparoscopic complications.

PMID- 11441997
TI  - Regarding: "splenectomy revised: manually assisted splenectomy with the dexterity
      device--a feasibility study in 22 patients" by Meijer et al.

PMID- 11441998
TI  - Thyroid-infiltrating B lymphocytes in Graves' disease are related to marginal
      zone and memory B cell compartments.
AB  - B lymphocytes that infiltrate the thyroid (Thy-B cells) in Graves' patients
      appear to be implicated in the pathophysiology of this disorder. The goal of the
      present study was to examine the nature of these Thy-B cells. To this end, Thy-B
      lymphocytes were isolated from surgical thyroidal samples, and their phenotype
      was determined by using mouse monoclonal antibodies (mAb) directed against a wide
      variety of surface markers, followed by flow cytometry multicolor analysis. The
      results show that most Thy-B cells (approximately 60%) exhibited IgM(+) IgD(low
      to -) surface immunoglobulin (Ig) profile, whereas the minor cell fraction
      (approximately 30%) consisted of switched IgG(+) memory B lymphocytes. Thy-B
      cells expressed low levels of CD5, CD23, and CD62L, which distinguished them from
      the resting B-cell pool, the major B-cell subset in the blood. In addition, they
      lacked CD38, CD10, and CD71, characteristic molecules for the germinal center B
      lymphocytes. In addition, Thy-B lymphocytes showed peculiar patterns both of
      adhesion molecules (CD62L(-), CD44(intermediate)), and of activation molecules
      (CD69(+), CD80(+), and, in part, CD95(+)). Taken together, these results suggest
      that the Thy-B lymphocyte subset consists of a combination of IgM(+) B cells
      resembling marginal zone B lymphocytes, and isotype-switched memory B cells.

PMID- 11441999
TI  - Whole-blood proliferation assay for autoimmune thyroid disease: comparison to
      density-gradient separated-peripheral blood lymphocytes.
AB  - Autoimmune thyroid diseases feature prominent cellular infiltration of the
      thyroid gland as well as autoantibody production to thyroid antigens. The most
      common assay to evaluate cell-mediated immunity is based on incorporation of
      tritiated thymidine into proliferating T cells after stimulation by the test
      antigens. In the past, cell proliferation assays of thyroglobulin (Tg) using
      peripheral blood mononuclear cells (PBMC) of individuals with autoimmune thyroid
      diseases required large quantities of blood and specialized separation
      techniques, and have not yielded high counts or high stimulation indices. We
      therefore developed a proliferation assay using less than 5 mL of whole blood and
      compared proliferation of cells in whole blood to that using PBMCs separated by
      density gradient centrifugation. We also determined if responses could be
      enhanced by addition of interleukin-2 (IL-2) to the cultures. We found that an IL
      2-stimulated proliferation assay to Tg using diluted whole blood is superior to
      the separated cell assay in detecting Tg-specific T-cell proliferation in
      autoimmune thyroid disease patients. Further refinement of this technique and
      larger trials may confirm its value for clinical investigation and special
      diagnostic applications.

PMID- 11442000
TI  - Thyroid stimulating hormone downregulates vascular endothelial growth factor
      expression in FRTL-5 cells.
AB  - We studied the regulation of the expression of vascular endothelial growth factor
      (VEGF) by TSH in monolayer cultures of rat thyroid FRTL-5 cell lines. The VEGF
      mRNA synthesis was significantly inhibited by TSH as well as dibutyryl cyclic
      adenosine monophosphate (cAMP) in a dose-dependent manner in FRTL-5 cells. This
      observation is contrary to previously published results using the thyroid
      follicular culture system. Our results suggest that the direct effect of TSH/cAMP
      is to inhibit the VEGF synthesis in monolayer cells.

PMID- 11442001
TI  - Thyroid hormone stimulates myoglobin expression in soleus and extensorum
      digitalis longus muscles of rats: concomitant alterations in the activities of
      Krebs cycle oxidative enzymes.
AB  - Myoglobin (Mb) gene expression, Citrate Synthase (CS) and Succinate Dehydrogenase
      (SDH) activities of Soleus (S) and Extensorum Digitalis Longus (EDL) muscles were
      studied in intact, thyroidectomized and T3-treated (25 microg/100g, BW, ip, 15
      days) rats. The fiber type composition of S muscle was also evaluated and used as
      control of the T3-induced effects. In the S muscle, the T3 treatment increased
      the Mb mRNA and protein expression, as well as the CS and SDH activity. These
      changes occurred parallel to the expected increase in type II (fast) and decrease
      in type I (slow)-fibers in S muscle. In the hypothyroid state, the Mb mRNA was
      decreased, while the Mb expression and CS activity tended to decrease. In
      contrast the SDH activity was increased, probably due to the enhanced motor
      activity that occurs as a short-term response to the hypothermia induced by
      hypothyroidism. In the EDL, the alterations were milder than those in S muscle in
      both thyroid states. These findings show that Mb gene expression is induced by
      T3. This is concomitant with the enhancement of Krebs Cycle enzyme activities and
      provides additional evidence that thyroid hormone increases the aerobic potential
      of skeletal muscles, as well as the speed of muscle contraction.

PMID- 11442002
TI  - Novel inactivating missense mutations in the thyrotropin receptor gene in
      Japanese children with resistance to thyrotropin.
AB  - We describe Japanese siblings with resistance to thyrotropin (TSH) who are
      compound heterozygotes for two novel mutations in the TSH receptor gene. The
      affected siblings had increased serum TSH, normal serum thyroid hormones, and
      normal positioned but slightly hypoplastic thyroid glands. The mutated paternal
      allele has the substitution of His (CAC) in place of Arg (CGC) at codon 450
      (R450H) of the TSH receptor. The mutated maternal allele has the substitution of
      Ser (AGT) in place of Gly (GGT) at codon 498 (G498S) of the TSH receptor. COS-7
      cells transfected with the R450H mutant exhibited a slightly decreased TSH
      binding and a slightly decreased cyclic adenosine monophosphate (cAMP) response
      to TSH, whereas cells transfected with the G498S mutant exhibited a markedly
      decreased TSH binding and a markedly decreased cAMP response to TSH. Flow
      immunocytofluorometry analysis demonstrated that the G498S mutant resulted in
      extremely low expression at the cell surface as compared with the wild type
      receptor and the R450H mutant, in spite of a normal intracellular synthesis. The
      present cases are the first Japanese patients with TSH resistance in whom
      mutations in the TSH receptor gene have been identified. These novel mutations
      may contribute to understanding of the struc-ture-function relationship of the
      TSH receptor.

PMID- 11442003
TI  - The use of oral radiographic contrast agents in the management of
      hyperthyroidism.
AB  - Oral iodinated radiographic contrast agents such as ipodate and iopanoic acid
      form an important part of the armamentarium used to treat hyperthyroidism. They
      rapidly and dramatically reduce serum triiodothyronine (T3) levels by inhibiting
      conversion of thyroxine (T4) to T3 in the periphery and by blocking secretion
      from the thyroid. Potential risks from the large iodine load resulting from their
      use limit their widespread applicability. In addition, they are ineffective when
      used alone on a long-term basis. However, these agents may be especially useful
      in treating thyrotoxic patients preoperatively, in neonatal Graves' disease, in
      massive levothyroxine ingestion, and when other conventional antithyroid drugs
      are unsuccessful or contraindicated.

PMID- 11442004
TI  - The use of three-dimensional ultrasound for thyroid volumetry.
AB  - Conventional two-dimensional (2-D) ultrasound is the standard method for the
      investigation of thyroid morphology. Volume calculations need model assumptions
      and are observer dependent. The present study performed with a commercially
      available three-dimensional (3-D) system Freescan added to a conventional
      ultrasound scanner compares the accuracy of conventional thyroid volumetry to
      several methods of 3-D volume determination. In vitro measurements were performed
      on thyroid phantoms with known volumes. The standard deviation of the normalized
      differences was 8.0% (3-D segmentation) and 10.5% (conventional). For the
      accuracy of volume determination in human thyroids we performed a postmortem
      study. The thyroid volume was calculated conventionally by the ellipsoid model
      and by two 3-D methods (segmentation and the newly developed multiplanar volume
      approximation). The reference volume was determined after resection by
      submersion. The standard deviation of the normalized differences was 26.9% for
      the conventional method, 9.7% for 3-D segmentation and 11.5% for the multiplanar
      volume approximation, showing significant better results for both 3-D methods and
      no significant difference between the 3-D methods. The 3-D system, therefore,
      achieves a better accuracy for thyroid volumetry than the conventional volumetry
      using planar images. In addition, the 3-D images are stored electronically and
      can be used for follow-up studies.

PMID- 11442005
TI  - Antithyroid drugs inhibit in vivo HLA-DR expression in thyroid follicular cells
      in Graves' disease.
AB  - Antithyroid drugs have been reported to reduce the expression of HLA-DR in
      thyrocytes in Graves' disease, but only circumstantial evidence has been provided
      about their in vivo immunologic effects. This present study was designed to
      examine the in vivo immunologic effect of antithyroid drugs on thyroid follicular
      cells. The study was conducted on 25 patients who had Graves' disease in
      remission or in activity and who were or were not receiving treatment (7 in overt
      thyrotoxicosis, 6 patients in remission, and 12 patients under medication). HLA
      DR expression in thyroid biopsies was verified by immunohistochemistry. The
      follicular cells of all patients in overt thyrotoxicosis expressed HLA-DR whereas
      those of patients in remission were negative for HLA-DR. HLA-DR was also not
      expressed in all patients under medication, but this did not correlate with the
      clinical evolution after thyroid drug withdrawal. In conclusion, antithyroid
      drugs inhibit follicular cell HLA-DR expression in Graves' disease, when
      thyrotoxicosis is controlled. This suggests that additional mechanisms not
      involving HLA-DR play a role in thyroid autoimmune disease.

PMID- 11442006
TI  - Ultrasound-guided fine-needle aspiration of the thyroid assessed by Ultrafast
      Papanicolaou stain: data from 1135 biopsies with a two- to six-year follow-up.
AB  - One of the limitations of fine-needle aspiration (FNA) of the thyroid is
      difficulty in distinguishing the follicular variant (FV) of papillary thyroid
      carcinomas (PTC) from follicular neoplasms. By highlighting the "Orphan Annie
      eyed" clear nuclei of the former, the Ultrafast Papanicolaou stain (UFP) easily
      separates these two entities. One thousand one hundred thirty-five ultrasound
      guided FNAs of the thyroid were assessed by UFP with immediate biopsy results
      reported to the patients in a busy radiology office in Manhattan from November
      1994 to December 1998. Of the 77 thyroid cancers resected, 22 were FVPTC and 17
      were microcarcinomas (1 medullary carcinoma, 16 PTC). The rates of
      "unsatisfactory," "cancer," "suspicious for cancer," "follicular neoplasm," and
      "benign" cytology were 0.7%, 4.4%, 2.6%, 10.2%, and 82.1%, respectively and the
      cancer yields at surgery were 98%, 81.8%, 15.8%, and 0% respectively. Of the 1127
      satisfactory FNAs in the series with a 2- to -6 years of clinical follow-up, a
      false-negative rate of 0% and a false-positive rate of 1.5% were obtained. Of the
      169 surgical follow-ups with satisfactory FNAs, a sensitivity of 100%,
      specificity of 66.7%, positive predictive value of 87.4%, negative predictive
      value of 100%, and global accuracy of 89.9% were achieved. The paradoxical
      combination of low unsatisfactory rate and low false-negative rate is attributed
      to (1) the use of needle puncture without syringe to obtain enough microfollicles
      from the exceedingly bloody aspirates from follicular neoplasms for a diagnosis,
      (2) eliciting history of neck trauma to confirm hematomas, (3) using UFP to
      highlight the grape-like watery clear nuclei of FVPTC evident with a 4x
      objective, and (4) the precise guidance by ultrasound in sampling
      microcarcinomas.

PMID- 11442007
TI  - An unusual presentation of follicular carcinoma of the thyroid.

PMID- 11442008
TI  - A new complication of hypothyroid coma: neurogenic dysphagia: presentation,
      diagnosis, and treatment.
AB  - We report the case of a patient with severe hypothyroid coma in whom hypothyroid
      related neurogenic oropharyngeal dysphagia was suspected, videoscopically
      confirmed, and successfully treated. This complication has not previously been
      described, and may have contributed to the historically high mortality associated
      with severe cases of hypothyroid coma. In the future, the early detection and
      aggressive treatment of this complication and its sequelae should ensure a
      further reduction in mortality from hypothyroid coma.

PMID- 11442009
TI  - Thyroglobulin-positive, radioiodine-negative thyroid cancer.

PMID- 11442010
TI  - Thyroid gland hemiagenesis with Graves' disease.

PMID- 11442011
TI  - Defining thyroid cell death.

PMID- 11442012
TI  - Vitamin D receptor gene polymorphisms in Hashimoto's thyroiditis.

PMID- 11442013
TI  - Studies on coronary arteriopathy in dogs following administration of CI-1020, an
      endothelin A receptor antagonist.
AB  - A selective nonpeptide endothelin A (ETA) receptor antagonist, CI-1020, was
      administered to beagle dogs intravenously (i.v.) for 4 hours to 4 weeks. One
      animal/sex received CI-1020 at 1 mg/kg/hr intravenously for 4, 8, or 24 hours to
      investigate onset of arteriopathy. Control animals (1/sex) received the vehicle
      only. To determine reversibility of arteriopathy, 8 dogs/sex were given CI-1020
      at 1 mg/kg/hr for 4 days. Two dogs/sex were sacrificed 1, 3, 8, and 29 days
      following cessation of infusion. Lesion development with prolonged exposure was
      investigated in 1 male dog. It was given CI-1020 by i.v. bolus at 120 mg/kg/day
      for 4 weeks and Monastral blue dye was administered i.v. to facilitate
      localization of vascular lesions. Coronary blood flow was determined in 4 dogs
      infused with CI-1020 at 0.3, 3, and 30 mg/kg for one hour at each dose.
      Macroscopically, hemorrhage or blue discoloration of Monastral blue was noted in
      the extramural coronary arteries along the coronary groove and atrium.
      Histologically, the earliest coronary changes were noted in animals sacrificed
      after 24 hours of treatment and characterized by medial hemorrhage and necrosis
      with a few infiltrating neutrophils. In the reversibility study, incidence and
      severity of arteriopathy was dependent on time of sacrifice following cessation
      of infusion. Acute necrotizing inflammation of arteries was present in all
      animals (n = 4) on day 1 postinfusion, whereas on day 8 postinfusion, lesions
      characterized by medial small pockets of trapped red cells, cell debris, and
      adventitial thickening were seen in 1 dog/sex. By day 29 postinfusion, coronary
      arteries were similar to controls. In the dog given daily i.v. bolus injections
      of CI-1020 for 4 weeks, arterial inflammatory lesions varied from acute to
      chronic, although most lesions were considered chronic active. Monastral blue
      pigments were noted in the wall of most arteries with chronic or chronic active
      lesions. Acute lesions were similar to those noted in day 1 postinfusion of the
      reversibility study. Medial smooth muscle necrosis and/or fibrosis with mixed
      inflammatory cell infiltrates characterized chronic or chronic active lesions.
      Smooth muscle proliferation and migration into the intima were also noted. There
      were no significant changes in coronary blood flow, coronary vascular resistance,
      or mean arterial blood pressure following CI-1020 infusion for 3 hours. In the 24
      hour infusion study, plasma endothelin 1 (ET-1) levels were mildly elevated (1.5
      4 fold) during CI-1020 infusion when compared to either pretest or control
      values. These results indicate that administration of endothelin antagonist (CI
      1020) to dogs was associated with development of coronary arteriopathy, which was
      completely resolved within 29 days following cessation of treatment. With
      prolonged (4-week) CI-1020 treatment, arterial lesions at varying stages of
      development (acute, chronic active, chronic) were seen, suggesting that tolerance
      to treatment (up to 4 weeks) does not occur.

PMID- 11442014
TI  - Toxicology studies with recombinant staphylokinase and with SY 161-P5, a
      polyethylene glycol-derivatized cysteine-substitution mutant.
AB  - SY 161-P5, a polyethylene glycol derivatized (PEGylated) mutant of the
      recombinant Staphylokinase (rSak) variant SakSTAR, exhibiting reduced
      antigenicity is in clinical development for treatment of acute myocardial
      infarction as a single bolus injection. A series of safety studies were performed
      in vivo as a routine toxicology program with SY 161-P5 (PEG-rSakSTAR) and with
      the recombinant Staphylokinase variant Sak42D (rSak42D). For both compounds,
      intravenous single bolus injections of up to 100-fold therapeutic equivalent, as
      well as repeated injections during 7 to 28 days revealed no significant
      pathological findings in mice, rats or hamsters. However, New Zealand white
      rabbits developed clinically silent, multifocal myocarditis following single or
      repeat doses of SY 161-P5 or of Sak42D. These findings were dose-independent and
      reversible. A similar species-specific cardiotoxic effect has previously been
      described for other proteolytic proteins, including the approved drugs
      Streptokinase and Acetylated Plasminogen Streptokinase Complex (APSAC). The large
      experience with these drugs, as well as the clinical data accumulated both with
      PEGylated and non-PEGylated rSak variants to date, do not indicate cardiotoxic
      hazards associated with the use of these drugs in humans.

PMID- 11442015
TI  - Morphological classification of dental lesions induced by various antitumor drugs
      in mice.
AB  - To characterize and compare maxillary incisor lesions caused by various antitumor
      drugs, male BALB/c mice were given a single intravenous injection of an estimated
      10% lethal dose (LD10)) of 5-fluorouracil (5-FU), adriamycin (ADR), mitomycin C
      (MMC), vinblastine sulfate (VBL). taxotere (TXR), irinotecan hydrochloride (CPT
      11), DX-8951f, or cisplatin (CDDP). After 3, 5, 10, 15, and 60 days, the animals
      were sacrificed, and the maxillary incisors were examined microscopically. The
      dental lesions observed were classified into 4 different types on the basis of
      their morphological features. The lesion due to 5-FU was characterized by focal
      defects in the dentin, and this injury was reversible (transient dentin injury).
      ADR- or MMC-induced lesions were defined by abnormal structure of the apical
      aspect of the tooth and irregular odontogenesis, lasting for a long period
      (persistent apical injury). Treatment with VBL or TXR showed irregular enamel
      formation and abnormal dentinogenesis. Their targets were considered to be both
      immature and mature odontogenic cells (diffuse dental injury). Exposure to CPT
      11, DX-8951f, or CDDP elicited minor reductions in a few precursor cells in the
      epithelial sheath on day 3, but no prominent dental abnormalities were seen
      thereafter (nontoxic injury). In conclusion, antitumor drugs can cause a variety
      of dental lesions that vary temporally and spatially, making histopathological
      examination of the maxillary incisor an important component of the safety
      assessment process for novel antitumor drugs.

PMID- 11442016
TI  - Immunohistochemical and ultrastructural studies of 2,6-dimethylaniline-induced
      nasal proliferative lesions in a rat two-stage nasal carcinogenesis model
      initiated with N-bis(2-hydroxypropyl)nitrosamine.
AB  - Proliferative lesions induced by 2,6-dimethylaniline (DMA) in a two-stage rat
      nasal carcinogenesis model were immunohistochemically and ultrastructurally
      investigated. Male F344 rats received diet containing 3,000 ppm DMA for 52 weeks
      after initiation with a single subcutaneous injection of 2400 mg/kg of N-bis(2
      hydroxypropyl)nitrosamine (DHPN). Histopathologically, proliferation of Bowman's
      glands, glandular hyperplasias, dysplastic foci, adenomas, and carcinomas were
      observed in treated rats. These nasal lesions mostly arose in the olfactory
      mucosa of the nasal cavity. Immunohistochemically, they were positive for
      cytokeratin and/or collagen type IV antibodies. Ultrastructurally,
      intracytoplasmic dense secretory granules (200-850 nm in diameter), identical to
      those in normal Bowman's glands, were observed in all the lesions, providing
      further support from an origin from these glands. Based on their cellular
      characterization, growth pattern and/or proliferative activity, two morphological
      continua were evident, one from dysplastic foci to carcinomas and the other from
      proliferation of Bowman's glands to glandular hyperplasias and adenomas. These
      results suggest that dysplastic foci arise from Bowman's glands and progress to
      carcinomas, while proliferation of Bowman's glands result in glandular
      hyperplasias and adenomas.

PMID- 11442017
TI  - Pathology of ocular irritation with bleaching agents in the rabbit low-volume eye
      test.
AB  - Despite differences in the processes leading to tissue damage, the ocular
      irritation response to various surfactants, two concentrations of an acid and an
      alkali, and an acetone, alcohol, aromatic amine, and aldehyde has been shown to
      depend on the extent of initial injury. The purpose of this study was to assess
      the extent to which this fundamental relationship exists for bleaching agents in
      the rabbit low-volume eye test. Ten microl of sodium perborate monohydrate
      (NaBO3), sodium hypochlorite (NaOCl), 10% hydrogen peroxide (H2O2), and 15% H2O2
      was applied directly to the cornea of the right eye of each rabbit. Macroscopic
      assessments for irritation were made 3 hours after dosing and periodically until
      35 days. Light microscopic examinations were conducted on tissues obtained at 3
      hr and on 1, 3, and 35 days. In vivo confocal microscopy (CM) and measurements of
      dead corneal epithelial cells and keratocytes at 3 hours and 1 day were used to
      characterize quantitatively initial corneal injury, while in vivo CM performed at
      3 hours and 1, 3, 7, 14, and 35 days was used to characterize quantitatively the
      corneal changes over time. The changes with NaBO3 and NaOCl were consistent with
      mild irritancy. For both, corneal injury was limited to the epithelium and
      superficial stroma. The changes with 10% H202 and 15% H2O2 were consistent with
      severe irritation. Both concentrations affected the epithelium and deep stroma,
      with 15% H2O2 also at times affecting the endothelium. However, unlike other
      irritants previously studied, with 10% H2O2 and 15% H2O2 there was an incongruity
      between the extent of epithelial and stromal injury, with stromal injury being
      more extensive than epithelial injury. A similar, although less dramatic, effect
      was observed with NaBO3. Additionally, there was still significant keratocyte
      loss at 35 days with 10% H2O2 and 15% H2O2 even though the eyes at times were
      considered to be macroscopically normal. These observations highlight the need to
      include both epithelial and stromal components in an ex vivo or in vitro
      alternative assay. In conclusion, these results continue to support and extend
      our hypothesis that ocular irritation is principally defined by the extent of
      initial injury despite clear differences in the means by which irritants cause
      tissue damage. Importantly, we have identified unique differences in the ocular
      injury and responses occurring with bleaching agents that are important to
      consider in the development and validation of alternative ocular irritation tests
      to characterize a broad range of materials differing in type and irritancy.

PMID- 11442018
TI  - Induction of pancreatic islet cell tumors in rats by repeated intravenous
      administration of 4-hydroxyaminoquinoline 1-oxide.
AB  - The inducibility of pancreatic islet cell tumors by administration of 4
      hydroxyaminoquinoline 1-oxide (4HAQO) was investigated in male 6-week-old Sprague
      Dawley rats. Rats were given 4HAQO intravenously at a weekly dose of 5 mg/kg 4
      times (group 1) or a single dose of 10 mg/kg (group 2). Control rats received the
      vehicle alone (group 3). Fifty-six weeks after the first 4HAQO administration,
      all surviving animals were killed and the pancreas was examined
      histopathologically, immunohistochemically and ultrastructurally. The incidences
      and multiplicities of islet cell tumors in groups 1, 2, and 3 were 52.3% (p <
      0.05 vs group 2, p < 0.01 vs group 3), 19.2% and 0%, and 0.70/animal (p < 0.05 vs
      group 2, p < 0.01 vs group 3), 0.23 and 0, respectively. Islet cell carcinomas
      were induced only in group 1, accounting for 6/44 (26%) tumors. Islet cell
      hyperplasias were found in 61.4% (p < 0.05 vs group 3), 42.3% and 10.0% of groups
      1, 2, and 3, with multiplicities of 0.95 (p < 0.05 vs groups 2 and 3), 0.54 and
      0.20, respectively. As compared with normal islets from control subjects, islet
      cell tumors showed an increase in the number of insulin positive cells associated
      with cytological features indicative of enhanced insulin synthesis and secretion,
      and a decrease in the number of glucagon positive cells without ultrastructural
      signs of modified secretory activity. Thus our results indicate that repeated
      intravenous administration of 4HAQO to rats is useful for the induction of islet
      cell tumors at high incidence.

PMID- 11442019
TI  - Hepatic toxicity and recovery of Fischer 344 rats following exposure to 2
      aminoanthracene by intraperitoneal injection.
AB  - Humans may be exposed to 2-aminoanthracene (2-AA), a substituted polycyclic
      aromatic hydrocarbon, and a recognized mutagen and carcinogen, through oral and
      respiratory routes from contact with a variety of environmental sources. For the
      present study, we sought to evaluate hepatic damage and recovery in Fischer 344
      rats following multiple i.p. injections of 5 mg of 2-AA. Rats were injected
      weekly for up to 5 weeks. Subgroups were then allowed to recover for 1, 5, or 9
      weeks, and biochemical and pathologic changes were evaluated. We observed that
      weight gains were reduced relative to controls for all groups receiving > or = 2
      injections. Serum enzyme levels indicative of liver damage were evident and
      included alterations in serum aspartate aminotransferase, alkaline phosphatase,
      total protein, albumin, and globulin. These alterations usually returned to
      normal by 5 weeks following cessation of 2-AA administration. In contrast,
      histologic liver changes, including hepatocyte hypertrophy, biliary hyperplasia
      with oval cell proliferation, altered foci, nodular hyperplasia, and one
      hepatocellular adenoma became more severe with time. This experiment demonstrates
      patterns of hepatic damage and recovery in rats exposed to 2-AA.

PMID- 11442020
TI  - Suppression of arylamine toxicity in the Fischer-344 rat following ingestion of a
      complex mixture.
AB  - The toxic effects of a mixture of 2-aminoanthracene (2-AA), benzanthracene (BA),
      and dinitropyrene isomers (DNP), and the toxic effects of these compounds
      individually, were investigated in the Fischer-344 rat following dietary exposure
      via a powdered basal diet. Animals were sacrificed at 14-, 30-, and 80-days of
      dietary exposure. Exposure to dietary 2-AA alone induced anorexia, cachexia,
      variable mortality, and altered serum chemistry profiles in the F-344 rat.
      Reduced lymphocyte counts were also shown in rats exposed to 2-AA. A temporal
      pattern of effect of 2-AA dietary exposure was observed in the progression of
      hepatic lesions in exposed animals. Dietary exposure to either DNP isomers or BA
      at a 10-fold higher concentration in the diet, relative to 2-AA, did not induce
      detectable toxic responses. However, exposure of rats to a mixture of 2-AA, BA,
      and DNP isomers (100 mg/kg, 1.0 g/kg, and 1.0 g/kg of diet, respectively)
      resulted in the attenuation of toxic effects when compared to exposure of F-344
      rats to 2-AA alone. These results indicate that the toxic effects of 2-AA are
      suppressed by co-administration of DNP and BA and suggest that compound
      interactions need to be considered when predicting the toxic potential of
      specific environmental pollutants.

PMID- 11442021
TI  - The effects of ad libitum overfeeding and moderate and marked dietary restriction
      on age-related spontaneous pancreatic islet pathology in Sprague-Dawley rats.
AB  - This study compared the effects of ad libitum (AL) overfeeding and moderate or
      marked dietary restriction (DR) on aged-related degenerative and proliferative
      changes of the endocrine pancreas in Sprague-Dawley (SD) rats. SD rats were fed
      Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68
      72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim
      necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2
      deoxyuridine (BrdU)-filled minipump implantation. Before each necropsy, glucose
      and serum insulin levels were measured. In addition to the routine
      histopathologic examination performed in both sexes, determination of 9
      pancreatic islet stereologic parameters was done in males at 13, 26, and 53
      weeks. In AL-fed rats, early changes in the islet morphology occurred, which
      resulted in a high incidence of islet fibrosis, focal hyperplasias and adenomas
      by two years. DR was dose-proportionally associated with decreased glucose and
      serum insulin levels, and delayed the onset, and decreased the incidence and
      severity of islet fibrosis and hyperplasia. Results of the stereology supported
      the histopathologic and clinical chemistry findings. It demonstrated that,
      compared to AL-fed rats, DR-fed rats had smaller pancreas, smaller pancreatic
      islets, smaller insulin secreting cell volumes, a lower degree of islet fibrosis
      and a lower islet cell BrdU labeling index, which correlated with a lower
      incidence of islet adenoma and carcinoma at study termination. Moderate and
      marked degrees of DR delayed the onset and severity of islet hyperplasia and
      fibrosis in a temporal- and dose-related manner. In contrast to marked DR, which
      dramatically prevented these changes, moderate DR delayed but not prevented onset
      of islet tumors. These findings support the concept that moderate DR results in a
      better-controlled animal model with a lower incidence or delayed onset of chronic
      spontaneous endocrine diseases in the rat bioassay.

PMID- 11442022
TI  - Metastasizing neuroblastomas from taste buds in rats transgenic for the Simian
      virus 40 large T antigen under control of the probasin gene promoter.
AB  - During establishment of a prostate cancer model in rats transgenic for the Simian
      virus 40 large T antigen, under control of the probasin gene promoter, with
      protein expression specific to the prostate, tongue, and spinal cord,
      undifferentiated small round cell tumors were frequently observed. Extensive
      examination of tongues of the transgenic rats, despite a macroscopically normal
      appearance, revealed the tumors to have come from taste buds of the papilla
      circumvallata and papilla foliata. The lesions were positive for the SV40 T
      antigen, PGP9.5 (ubiquitin C-terminal hydrolase), and synaptophysin, neuron and
      neuroendocrine markers. Morphologically and immunohistochemically, the tumors
      were diagnosed as neuroblastomas, considering the neuroepithelial origin.
      Histologically identical tumor cells in the spinal cord and lung were observed
      only in the rats with deeply invading tongue tumors, suggesting that metastasis
      from the tongue tumors had occurred. Castration or supplementation with
      testosterone propionate did not alter tumor development, indicating the tumors to
      be androgen-independent. These results clearly show that taste buds can give rise
      to metastasizing neuroblastomas.

PMID- 11442023
TI  - Cellular and cytokine responses in the circulation and tissue reactions in the
      lung of rhesus monkeys (Macaca mulatta) pretreated with cyclosporin A and
      challenged with staphylococcal enterotoxin B.
AB  - Cyclosporin A (CsA), an inhibitor of T cell cytokine production, protects mice
      against staphylococcal enterotoxin B (SEB) intoxication. To determine whether CsA
      treatment would work in a species closer to humans. 4 rhesus monkeys were given
      50 mg/kg CsA followed by an intratracheal challenge with approximately 6 LD50 of
      SEB. The CsA was not protective: one of the monkeys died and the other three had
      to be euthanised when they became moribund. All monkeys made IL-2, TNF, and IFN
      gamma in response to SEB. In addition, there was about a 10-fold increase in ACTH
      levels 2 hr after SEB challenge. CsA significantly suppressed in vitro
      proliferation of lymphocytes from treated monkeys. Both CsA-treated monkeys and
      monkeys that had been challenged in a previous experiment with a lethal dose of
      SEB but had received no cyclosporin had pathologic changes in several organs. The
      most prominent changes were marked edema and leukocytic infiltration of the
      bronchial and bronchiolar mucosa. The CsA treatment appeared to reduce the
      intensity of lung inflammation, but this effect was not sufficient to protect the
      monkeys. The results suggest that CsA alone may not be an effective therapeutic
      agent for humans suffering from SEB intoxication or gram-positive septic shock.

PMID- 11442024
TI  - Rat kidney pathology induced by chronic exposure to fumonisin B1 includes rare
      variants of renal tubule tumor.
AB  - The carcinogenicity of fumonisin B1 (FB1), a worldwide contaminant of corn
      produced by Fusaria species of fungi, has been tested recently in 2-year feeding
      studies in Fischer F344 rats and B6C3F1 mice. Inclusion of FB1 at 50 and 80 ppm
      in the diet induced liver tumors in female mice, and at 50 and 150 ppm induced
      renal tumors in male rats (22). In the present study, the kidneys from the rat
      bioassay were examined to characterize the various histopathological changes
      associated with renal tumor induction. In all high-dose (150 ppm) and mid-dose
      (50 ppm) male rats, and to a lesser extent in high-dose (100 ppm) female rats,
      there was evidence of sustained nephrotoxicity manifested as basophilia,
      apoptosis, cell regeneration, and simple tubule hyperplasia, affecting proximal
      convoluted tubules in the deep cortex, extending into the outer region of the
      outer stripe of outer medulla. A further alteration consisted of sporadic areas
      of interstitial hyalinization in deep cortex, suggestive of expanded basement
      membrane, coupled with tubule atrophy. The continued presence of nephrotoxicity
      throughout chronic exposure to FB1 suggested that renal tumor development may
      have been an outcome of sustained cell loss and compensatory regeneration. In
      some cases, preneoplastic tubules or incipient renal tumors presented an immature
      or fetal form in association with interstitial hyalinization. The renal tubule
      tumors induced by FB1 were typified by a rare, highly malignant, anaplastic
      variant capable of growth by infiltration. Of the 10 renal tubule tumors
      diagnosed in the mid-dose males, and the 16 in the high-dose males, 8 and 10,
      respectively, were graded as carcinomas. Anaplastic variants represented 50% of
      the mid-dose carcinomas and 80% of the high-dose carcinomas. One of the
      anaplastic carcinomas in a mid-dose male was a true sarcomatoid phenotype not
      previously recorded in the rodent. Metastatic invasion of the lung occurred with
      25% of the mid-dose carcinomas and 50% of the high-dose carcinomas. It was
      speculated that FB1 may have been influencing the growth characteristics of the
      induced renal tumors via its inhibitory action on the synthesis of sphingolipids,
      which in turn, participate in regulating cell contact, growth, and
      differentiation, or alternatively by affecting cell adhesion molecules.

PMID- 11442025
TI  - An in vivo method for using 5-bromo-2'-deoxyuridine (BrdU) as a marker of
      chemically-induced hepatocellular proliferation in the Japanese medaka (Oryzias
      latipes).
AB  - Japanese medaka fish (Oryzias latipes) were used to develop an in vivo method to
      assess hepatocellular proliferation in a nonmammalian model. Proliferative
      responses were assessed in medaka at 7, 17, 24, and 94 days after a 48-hour
      exposure to 10 or 100 mg/L diethylnitrosamine (DEN). Subgroups of medaka were
      exposed to 50 or 75 mg/L of 5-bromo-2'-deoxyuridine (BrdU) in water for 72 hours,
      sacrificed, and then processed for immunohistochemical staining. Proliferative
      indices of BrdU-labeled hepatocytes were quantified and compared using both count
      and area measurements. There was a significant increase (p < 0.05) in
      hepatocellular proliferation in the 100 mg/L DEN-treated fish as compared to
      controls and 10 mg/L DEN-treated fish for the first 3 time points.
      Hepatocarcinogenicity was evaluated 26 weeks post-DEN exposure. There was a
      significant increase (p < 0.0001) in hepatocellular neoplasms in 100 mg/L DEN
      treated fish compared to other fish. Effective BrdU-labeling of S-phase
      hepatocytes in medaka was achieved by adding BrdU to the aquarium water, and an
      increase in hepatocellular proliferation using this method was detected 7 days
      after exposure to a carcinogenic concentration of DEN. Additionally, the new
      method of area measurement indices of proliferation were as precise as count
      indices (R2 > or = 0.92).

PMID- 11442026
TI  - "Have you seen this?" Diffuse hepatic apoptosis.
AB  - One important cell death pathway involves binding of the cell surface receptor
      Fas, which recruits and activates specific initiator and effector caspases. In
      this study Balb/c mice were injected with monoclonal antibody to Fas either alone
      or followed by the tripeptide caspase inhibitor Z-VAD.fmk. At four hours mice
      were killed along with concurrent controls and tissues processed for histological
      examination and immunocytochemical staining for cleaved caspase-3. The livers in
      all animals treated with Fas alone showed massive apoptosis and positive staining
      for cleaved caspase-3 whereas those treated with Fas and Z-VAD.fmk or controls
      showed little or no apoptosis or staining for cleaved caspase-3. These features
      suggest that massive apoptosis may be important in fulminant liver disease.

PMID- 11442027
TI  - "Have you seen this?" Intralobular hepatocellular hyperplasia in Yucatan
      minipigs.

PMID- 11442028
TI  - Retention and mass transfer characteristics in reversed-phase liquid
      chromatography using a tetrahydrofuran-water solution as the mobile phase.
AB  - The characteristics of the retention and the mass transfer kinetics in reversed
      phase liquid chromatography (RPLC) were measured on a system consisting of a C18
      silica gel and a tetrahydrofuran-water (50:50, v/v) solution. These parameters
      were derived from the first and the second moments of the elution peaks,
      respectively. Further information on the thermodynamic properties of this system
      was derived from the temperature dependence of these moments. Some correlations
      previously established were confirmed for this system, namely, an enthalpy
      entropy compensation for both retention and surface diffusion and a linear free
      energy relationship. These results are compared with those observed in other
      similar systems using methanol-water (70:30, v/v) and acetonitnile-water (70:30,
      v/v) solutions. The contribution of surface diffusion to intraparticle diffusion
      in C18-silica gel particles was shown to be important. The analysis of the
      thermodynamic properties of surface diffusion suggests that, in these three RPLC
      systems, its activation energy is lower than the isosteric heat of adsorption.
      The nature and the extent of the influence of the mobile phase composition on the
      parameters describing the retention and the mass transfer kinetics are different
      but the chromatographic mechanisms involved in RPLC systems appear similar,
      irrespective of the nature of the organic modifier in the mobile phase.

PMID- 11442029
TI  - Characterization of dynamically prepared phospholipid-modified reversed-phase
      columns.
AB  - We have modified a reversed-phase (RP8) column by passing through it an aqueous
      solution of phosphatidylcholine-based liposomes. The phospholipids from the
      liposomes adsorb onto the octyl chain of the stationary phase, thus altering the
      nature of the stationary phase and of the chromatographic interactions. The
      properties of the phospholipid-modified column were investigated using solutes
      belonging to several chemical classes. We found that the retention factors of
      negatively and positively charged solutes decreased as the amount of phospholipid
      in the column was increased. For the solutes studied here the extent of the
      decrease was smaller for the positive solutes. With neutral solutes, the
      retention factors of some (benzenediols) increased markedly while with others
      (ketones) the retention factors decreased. The selectivities between the various
      solutes on the phospholipid-modified column were different than on the original
      reversed-phase column. The retention behavior of the solutes can be explained in
      terms of (1) effective shielding of the hydrophobic part of the stationary phase
      by the polar head groups of the phospholipids and (2) hydrogen bond formation
      between the solutes and the carbonyl oxygens as well as the non-ester phosphate
      oxygens in the polar head groups of the phospholipids.

PMID- 11442030
TI  - Study of the polymerization of anthracene oil with AlCl3 by chromatography and
      related techniques.
AB  - The structure and composition of products from the reaction of anthracene oil
      with anhydrous AlCl3 have been examined. Size-exclusion chromatography has been
      carried out using a column with polystyrene-polydivinylbenzene as stationary
      phase, 1-methyl-2-pyrrolidinone at 80 degrees C as eluent and variable-wavelength
      UV-absorption detection. This system provides a chromatogram of the sample with
      several peaks. Molecular masses corresponding to these peaks were estimated using
      a calibration curve obtained with polycyclic aromatic hydrocarbon standards,
      ranging from 92 to 532 u. The most abundant compounds of the substrate were
      dimers and trimers of the main anthracene oil components. These results are
      corroborated on a qualitative level by synchronous UV-fluorescence spectra.

PMID- 11442031
TI  - Reversed-phase and size-exclusion chromatography as useful tools in the
      resolution of peroxidase-mediated (+)-catechin oxidation products.
AB  - The peroxidase-catalysed oxidation of plant phenolics involves one-electron
      oxidation reactions, and yields unstable mono-radical species, which couple to
      generate heterogeneous product mixtures of different degrees of polymerisation.
      One such phenolic susceptible to oxidation by peroxidase is (+)-catechin. Low
      pressure chromatography on Sephadex LH-20, using methanol as mobile phase,
      resolves the main peroxidase-mediated (+)-catechin oxidation products into a
      dimeric compound (dehydrodicatechin A) and an oligomeric fraction with a
      polymerisation degree equal or greater than 5. These pure fractions were used to
      develop rapid high-performance liquid chromatographic methods, both reversed
      phase and size-exclusion chromatography for the direct analysis of the peroxidase
      mediated (+)-catechin oxidation products. The joint use of both chromatographic
      systems permitted the qualitative and quantitative identification of the
      peroxidase-mediated (+)-catechin oxidation products, and can thus be considered
      as a useful tool for analysing the complex mixtures of natural bioactive plant
      products synthesized in reactions catalyzed by plant peroxidases.

PMID- 11442032
TI  - Determination of estrogens in river water by gas chromatography-negative-ion
      chemical-ionization mass spectrometry.
AB  - A method for the determination of estrogens (17alpha-estradiol, 17beta-estradiol,
      estrone, ethynyl estradiol, and estriol) as pentafluorobenzyl-trimethylsilyl (PFB
      TMS) derivatives by gas chromatography-mass spectrometry (GC-MS) with negative
      ion chemical-ionization (NICI) is described. The NICI of all the derivatives
      produced an intense [M-PFB]- ion as the base peak. The reagent gas (methane) flow
      rate and the ion source temperature were determined to be 2.0 ml/min and 240
      degrees C, respectively, for the optimized NICI-selected ion monitoring (SIM)
      conditions. The sensitivities of the PFB-TMS derivatives in the NICI mode were
      8.0-130 times higher than those of the PFB-TMS derivatives in electron ionization
      (EI) mode, and 12-25 times higher than those of all the TMS derivatives in the EI
      mode. This method was applied to the analysis of estrogens in river water using a
      solid-phase extraction as the sample preparation. The recoveries of the target
      chemicals from a river-water sample spiked with standards at 2 ng/l level were
      85.8-126.5% (RSD, 6.2-13.0%). The methodical detection limits ranged from 0.10 to
      0.28 ng/l.

PMID- 11442033
TI  - Improvement of the analysis of dansylated derivatives of polyamines and their
      conjugates by high-performance liquid chromatography.
AB  - The paper described a method for improving the hydrolysis of conjugated
      polyamines in PH fraction, isolated from the lichen Evernia prunastri, as well as
      the optimization of dansylation procedure of these polyamines on the basis of the
      pH value to which derivatization is achieved. Dansylated polyamines have been
      later separated by high-performance liquid chromatography (HPLC) using a gradient
      elution. Hydrolysis of conjugates requires acid treatment at room temperature
      rather than at 110 degrees C, as usually described. Dansylation is improved at
      high pH values, whereas removal of phenolics (mainly evernic acid), from the
      conjugates requires low pH values.

PMID- 11442034
TI  - Analysis of sulfophthalimide and some of its derivatives by liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - A system was developed for the separation of sulfophthalimide (SPI),
      sulfophthalamide (SPAM), sulfophthalamic acid (SPAA) and sulfophthalic acid (SPA)
      by ion-pair liquid chromatography and their detection by electrospray ionization
      tandem mass spectrometry (ESI-MS-MS). Except for SPAM, the 3- and 4-sulfo-isomers
      of the analytes were separated by HPLC using volatile tributylamine as ion
      pairing agent. Initial fragmentations of the analytes in the negative mode
      involve losses of CO2 or HNCO or condensation via H2O or NH3 elimination. ortho
      Effects of the sulfonate group were recognized in the fragmentation of the
      respective 3-sulfo-isomers and allowed us to assign the order of elution of the
      SPAA isomers. Quantitative analysis of these sulfonated aromatic compounds with
      MRM detection was elaborated and resulted in detection limits ranging from 1 pg
      for SPA to 13 pg for SPAA isomers and in limits of quantification of 2-10
      microg/L for 5 microL volumes of injected tap water, municipal wastewater or
      industrial effluents up to salt contents of 0.5-1 g/L. The method was applied to
      study the isomer-specific chemical and microbial transformations of SPI, which
      was previously shown to be formed by white-rot fungi from sulfophthalocyanine
      textile dyes.

PMID- 11442035
TI  - Analysis of glucosinolates from broccoli and other cruciferous vegetables by
      hydrophilic interaction liquid chromatography.
AB  - While methods for the identification and quantification of total plant
      glucosinolate content typically utilize desulfation of glucosinolates followed by
      reversed-phase chromatography, the analysis of intact glucosinolates has been
      problematic. Hydrophilic interaction chromatography offers a novel method for
      analyzing intact glucosinolates and when performed along with ion-pair reversed
      phase chromatography offers a powerful and complementary method for glucosinolate
      analysis.

PMID- 11442036
TI  - Simple high-performance liquid chromatography method for alpha-tocopherol
      measurement in Rosmarinus officinalis leaves. New data on alpha-tocopherol
      content.
AB  - A simple HPLC method for vitamin E (alpha-tocopherol) measurement in the leaves
      of Rosmarinus officinalis has been developed and validated. It has enabled new
      data for alpha-tocopherol content to be established. The leaves, recently
      harvested, were dried in a microwave oven and crushed; then, alpha-tocopherol was
      directly extracted from portions of ground material with acetone, by probe
      sonication. After centrifugation the acetonic extract was analysed by HPLC with
      ergocalciferol (vitamin D2) added as internal standard and a gradient elution
      with a Nucleosil C18 column at 35 degrees C. Validation parameters of the method
      can be considered adequate. For standards: linearity is r=0.999, recovery is
      100+/-2%, intra-assay precision has RSD=+/-3% and inter-assay precision has
      RSD=+/-6%. For samples: linearity is r=0.99, recovery: 93+/-7%, intra-assay
      precision has RSD=+/-4% and inter-assay precision has RSD=+/-7%.

PMID- 11442037
TI  - Integrated pulsed amperometric detection of glufosinate, bialaphos and glyphosate
      at gold electrodes in anion-exchange chromatography.
AB  - A rapid and practical method for direct detection of the herbicides (glufosinate,
      bialaphos and glyphosate) in anion-exchange chromatography has been developed
      with integrated pulsed amperometric detection (IPAD). The electrochemical
      behavior of these herbicides showed catalytic currents based on the oxidation of
      amines in their structures. Waveform in IPAD was similar to that for amino acids,
      which exhibited adsorption/desorption catalytic features at gold electrode
      surface in alkaline solution. Under optimized conditions, detection limits
      (signal-to-noise ratio of 3) for glufosinate, bialaphos and glyphosate were 20,
      65 and 50 ng ml(-1), respectively, with correlation coefficients of 0.995, 0.997
      and 0.996 over concentration ranges of 0.1-45, 0.3-32 and 0.1-50 microg ml(-1),
      respectively. The relative standard deviations (n=5) were 1.7-3.0%. The present
      method was successfully applied to the determination of glyphosate in urine and
      serum.

PMID- 11442038
TI  - Retention behaviour and fluorimetric detection of procaine hydrochloride using
      carboxymethyl-beta-cyclodextrin as an additive in reversed-phase liquid
      chromatography.
AB  - The retention behaviour of procaine hydrochloride on an Alltima octadecyl silica
      (C18) column, with a mobile phase containing negatively charged carboxymethyl
      beta-cyclodextrin (CM-beta-CD), influenced by a combination of hydrophobic and
      electrostatic interactions was systematically investigated. Various factors
      affecting the retention of procaine on the C18 column such as the concentration
      of CM-beta-CD, pH and the methanol percentage in the mobile phase, were studied.
      An equation was applied to estimate the apparent binding constant of the CM-beta
      CD-procaine inclusion complex as an aid for understanding the retention
      mechanism. The first analytical application of CM-beta-CD as a mobile phase
      additive for the determination of procaine was developed. The calibration curve
      was linear in the range 22-1360 ng ml(-1) with an RSD of 2.1%. The detection
      limit based on 3sigma was 1 ng ml(-1) with fluorimetric detection at the
      excitation and emission wavelengths of 305 nm and 350 nm, respectively. The limit
      of quantitation based on 10sigma was 22 ng ml(-1). The proposed method has been
      successfully applied to real sample analysis.

PMID- 11442039
TI  - Sensitive determination of metal ions by liquid chromatography with tris(2,2'
      bipyridine) ruthenium (II) complex electrogenerated chemiluminescence detection.
AB  - Emetine dithiocarbamate metal complex, which is prepared from emetine, carbon
      disulfide, and metal (II), was found to indicate a large chemiluminescence
      intensity on the electrogenerated chemiluminescence of tris(2,2'
      bipyridine)ruthenium(II). Liquid chromatography equipped with the
      chemiluminescence detection was developed for analyzing trace metal ions by use
      of the metal complex formation. The mixture of the Cu(II) and Co(II) complexes as
      a model sample was injected into the LC system. The two metal complexes and an
      excess emetine were successfully separated. The Cu(II) and Co(II) complexes were
      determined over the range 1-300 nM (the detection limit of 650 fg) and 30-5000 nM
      (the detection limit of 17 pg), respectively.

PMID- 11442040
TI  - Gravitational field-flow fractionation for the characterisation of active dry
      wine yeast.
AB  - Gravitational field-flow fractionation (GrFFF) is applied to the fractionation of
      active dry wine yeast. An experimental approach to the analysis of the effects
      that field variation by changing mobile phase composition and flow-rate have on
      the fractionation process of standard particles (polystyrene) was first developed
      to further obtain effective fractionation of wine yeast by GrFFF. Scanning
      electron microscopy and Coulter counter particle size measurements were used to
      monitor the fractionation extent and capabilities of GrFFF to describe the
      distribution of yeast cells populations.

PMID- 11442041
TI  - Study of the mechanism of the interaction of vinyl chloride with water by
      reversed-flow gas chromatography.
AB  - The investigation of the mechanism for the interaction of vinyl chloride (VC)
      with liquid foods is of great significance in food science. In the present work
      the model system VC-water was studied by using the relatively new technique of
      reversed-flow gas chromatography. Using suitable mathematical analysis the
      following physicochemical quantities were determined: (a) diffusion coefficients
      of VC into water, (b) overall mass transfer coefficients of VC in the water, and
      in the carrier gas nitrogen, (c) partition coefficients of VC between water and
      nitrogen, and (d) constants of Henry's law for the adsorption of VC by water.
      From the variation of the above parameters with temperature, and the stirring
      rate of the water, useful conclusions concerning the mechanism for the VC-water
      interaction were extracted. The experimental results for the transfer of VC into
      the bulk water suggest (i) a mechanism consisted of a fast equilibrium step
      between the VC in the gas phase and in the interface, followed by a slow
      adsorption of VC into the bulk of water, which is the rate-determining step, when
      the water is quiescent, and (ii) a mechanism consisted of a slow diffusion of VC
      from the gas phase to the interface, which is the rate-determining step, followed
      by a fast equilibrium step between the VC in the interface and in the water bulk,
      when the water is stirred.

PMID- 11442042
TI  - Effect of efficiency improvement by injecting a sample at a lower carrier gas
      velocity in isothermal gas-liquid chromatography.
AB  - The effect of efficiency improvement of chromatographic system by injecting a
      sample at a lower carrier gas velocity (in comparison with the carrier gas
      velocity at subsequent separation) was studied experimentally and theoretically
      in isothermal gas-liquid chromatography. The suggested technique is based on
      sample introduction in the programmed carrier gas velocity operation mode: the
      injection is realized at low carrier gas velocity, then the velocity is increased
      rapidly up to the operation value. The technique can be applied in
      chromatographic practice.

PMID- 11442043
TI  - Application of programmed-temperature split/splitless injection to the trace
      analysis of aliphatic hydrocarbons by gas chromatography.
AB  - The dependence of the programmed-temperature solvent split sampling technique
      using a PSS (programmed-split/splitless) injection mode on different variables
      affecting the introduction of large sample volumes for a mixture of alkanes in
      capillary GC was evaluated. Apart from the studies found in the literature on
      different factors such as speed of injection. presence of adsorbent in the liner,
      internal diameter of the liner, initial and final injector temperature, split
      flow-rate and initial split time, affecting the chromatographic signal of
      different compounds, others were studied whose influence has not been considered
      until now. They include length of the microsyringe needle, adsorbent distribution
      in the liner, injection volume on analyte discrimination, speed of injector
      heating, time which the column stays at the initial temperature and time that the
      injector stays at the final temperature. Once finalised, the study of the PSS
      injection mode was compared with the conventional mode of gas chromatography
      splitless injection, and found that the proposed method increases sensitivity in
      GC trace analysis. Finally, the application of both injection modes in the
      determination of aliphatic hydrocarbons was tested in an atmospheric particulate
      sample.

PMID- 11442044
TI  - Use of deactivated fused-silica capillary precolumns in pesticide analysis by gas
      chromatography with electron-capture detection.
AB  - The advantages and disadvantages of coupling a retention gap of fused-silica
      between the injection port and the chromatographic column are discussed. The
      influence on the peak width and height of several factors such as the solvent (n
      hexane, acetone, ethyl acetate and methanol), the gap (length, inner diameter,
      deactivation mode), the injection volume and the pesticide concentration has been
      examined. Those factors have very different incidences so, it is not possible to
      extract a general recommendation about the use of gaps. For this reason, checking
      its viability in each particular case is more advisable.

PMID- 11442045
TI  - Application of static liquid-phase microextraction to the analysis of
      organochlorine pesticides in water.
AB  - Static liquid-phase microextraction, with subsequent analysis by gas
      chromatography-electron-capture detection, has been applied to extract eight
      organochlorine pesticides from water. A conventional microsyringe was used to
      extract analytes from water samples over a concentration range of 0.05-100
      microg/l. Factors relevant to the extraction process were investigated. The
      sensitivity of the method was enhanced with agitation, and increasing the
      extraction temperature, of the sample solution. Concentration factors of >50-fold
      were easily achieved within 25 min of extraction. The analytical data exhibited a
      relative standard deviation (RSD) range of 3.2% (lindane) to 10.7% (methoxychlor)
      for the eight pesticides; most RSD values were under 7%. Water samples collected
      from a reservoir, and from tap water in a chemical laboratory were analyzed using
      the procedure.

PMID- 11442046
TI  - Analysis of alkali-lignin in a paper mill effluent decolourised with two
      Streptomyces strains by gas chromatography-mass spectrometry after cupric oxide
      degradation.
AB  - Alkali-lignin samples obtained from an untreated paper mill effluent and from the
      effluent decolourised by the strains Streptomyces avermitilis CECT 3339 and
      Streptomyces scabies UAH 51 were analysed by gas chromatography-mass spectrometry
      (GC-MS) after cupric oxide degradation. The analysis of the depolymerisation
      products of the alkali-lignin from the decolourised effluents showed a strain
      specific modification of the aromatic moiety of the alkali-lignin. Moreover, both
      strains were able to breakdown the aryl-alkyl ether linkages between the cinnamic
      acids and the lignin. Finally, GC-MS analysis showed that both strains oxidised
      the alkali-lignin regardless of its initial degree of oxidation.

PMID- 11442047
TI  - Prediction of electrophoretic behaviour of a series of quinolones in aqueous
      methanol.
AB  - Quinolones are a family of antibacterial agents used in human and veterinary
      clinics. The examination of protonation equilibria is essential because their
      antibacterial activity is pH-dependent. In this work, dissociation constants of
      quinolones in MeOH-water mixtures were obtained using capillary electrophoresis.
      The method is based on a model that relates electrophoretic mobility of the
      solute with pH. The effect of pH, pKa and activity coefficient on electrophoretic
      behaviour was considered. Standard pH values for buffer solutions were previously
      determined in MeOH-water mixtures, and the pH can thus be measured in these media
      as in water. This model is also used to obtain the optimum conditions for the
      separation of a series of substances because it allows one to predict the
      resolution between adjacent peaks from a few experimental data.

PMID- 11442048
TI  - Use of eosin as a fluorophore in capillary electrophoresis with laser detection.
AB  - Eosin has been used to generate the background signal for indirect fluorimetric
      detection of inorganic and organic ions, simultaneously separated by capillary
      zone electrophoresis (CZE). This reagent provides constant fluorescence over the
      pH range of 5-10 and is compatible with the excitation by an argon ion laser at
      488 nm with emission at 520 nm. The use of esosine as fluorophore, H3BO3, and
      Na2B4O7 as electrolyte and diethylentriamine as modifier of the electroosmotic
      flow in CZE were optimised. The analytical potential of the studied buffer was
      tested on a group of 12 anions, used as model compounds. Both, hydrodynamic and
      electrokinetic injection mode were optimised. The detection limits determined by
      the last injection mode, were in the range 0.008-0.037 mg l(-1). By using this
      method, the quantitation of the common anions in tap and mineral water has been
      carried out successfully.

PMID- 11442049
TI  - Isotachophoretic separation behavior of rare-earth EDTA chelates and analysis of
      minor rare-earth elements in an iron ore by bidirectional isotachophoresis
      particle-induced X-ray emission.
AB  - Mobilities of 16 anions of rare-earth-EDTA 1:1 chelate (RE-EDTAs) were
      isotachophoretically measured by using two leading electrolytes (pH 3.6 and 6.0)
      in order to assess their separation behavior. The leading electrolyte was 20 mM
      hydrochloric acid. The pH of the solution was adjusted to 3.6 by adding beta
      alanine and to 6.0 by adding histidine. The obtained mobilities were very close
      to each other in the range 20.1x10(-5)-21.9x10(-5) cm2 V(-1) s(-1) with the
      minimum mobilities for Pr-EDTA and Nd-EDTA for pH 3.6 and 6.0, respectively, and
      pH dependence was hardly observed. On the basis of the above knowledge. minor
      rare-earth elements in a standard iron ore sample were determined as RE-EDTAs by
      bidirectional isotachophoresis-particle-induced X-ray emission (PIXE), where the
      Fe(II) matrix digested by alkali fusion was separated as Fe(II)Phen3(2+) (phen =
      1,10-phenanthroline). Since 5% of the total iron was still detected as
      Fe(III)EDTA- and might disturb PIXE analysis of RE-EDTA-, itaconic acid was used
      as the spacer for Fe(III)EDTA- and RE-EDTA-. The fractions of RE-EDTA- were
      successfully analyzed off-line by a multielemental analytical method, PIXE
      [analytical result (3.62% (w/w) as RE2O3]; the nominal value was 3.37% (w/w) as
      RExOy.

PMID- 11442050
TI  - Chiral separations of transition metal complexes using capillary zone
      electrophoresis.
AB  - Several buffer additives that may facilitate chiral separation for optically
      active transition metal (TM) systems are investigated using capillary zone
      electrophoresis. The TM complexes evaluated exhibit considerable heterogeneity
      with respect to total complex charge (0 to 4+), ligand type, and identity of the
      central metal including Ru2+, Ni2+, Cr3+, and Co3+, threo-D[+]-Isocitrate,
      potassium antimonyl-d-tartrate and dibenzoyl-L-tartrate are identified as the
      most efficient chiral selectors. Interestingly, TM complexes exhibiting a (3+)
      total complex charge exhibit a reversal of enantiomer elution order versus all
      other complexes when separated using the tartrate additives. Operating parameters
      including pH, temperature, and capillary length are discussed, and chiral
      separations of complex mixtures are demonstrated.

PMID- 11442051
TI  - Determination of scutellarin in Erigeron breviscapus extract by liquid
      chromatography-tandem mass spectrometry.
AB  - A quantitative assay for scutellarin by LC-MS-MS (negative ion mode) was
      developed. The scutellarin was extracted from dry Erigeron breviscapus.
      Significant ion suppression was observed, which could be eliminated by increasing
      the turboionspray interface temperature to 350 degrees C and by 1000-fold
      dilution of the extract with solvent. The calibration curve of scutellarin showed
      excellent linearity over a wide concentration range (0.01-100 microg/ml)
      (r=0.998), and the limit of detection was 15 pg/ml using a 10-microl injection
      volume. The analysis time was 4 min/sample.

PMID- 11442052
TI  - Large-scale separation of resveratrol, anthraglycoside A and anthraglycoside B
      from Polygonum cuspidatum Sieb. et Zucc by high-speed counter-current
      chromatography.
AB  - High-speed counter-current chromatography was successfully applied to the large
      scale separation of resveratrol, anthraglycoside A and anthraglycoside B from the
      crude extract of Polygonum cuspidatum Sieb. et Zucc using a two-phase solvent
      system composed of chloroform, methanol and water. Resveratrol, anthraglycoside A
      and anthraglycoside B were separated from multigram quantities (5 g) of crude
      extract of P. cuspidatum. The separation yielded 200 mg to 1 g of these three
      compounds each at over 98% purity as determined by HPLC. The chemical structures
      of these components were identified by nuclear magnetic resonance (NMR) and MS.

PMID- 11442053
TI  - Chromatin structure and phaseolin gene regulation.
AB  - Chromatin structure, the organized packaging of DNA with histones in the nucleus,
      is now seen as a dynamic fabric that changes with development. Here, we use
      studies on the phaseolin (phas) gene that encodes a seed protein to show how
      chromatin structure interacts with the transcription machinery to accomplish
      rigorous spatial regulation of expression. In leaf and other vegetative tissues,
      a nucleosome is rotationally and translationally positioned over an ensemble of
      three phased TATA boxes, denying access to TBP. Current interest focuses on the
      mechanisms by which this architecture is remodeled during embryogenesis. The
      transcription factor PvALF is intrinsically involved, as are other non-histone
      proteins and abscisic acid. These concepts, and the possible modular nature of
      phas expression, are summarized together with speculations concerning the re
      establishment of the nucleosome over the phas promoter during terminal stages of
      embryogenesis.

PMID- 11442054
TI  - Promoter analysis of the nuclear gene encoding the chloroplast glyceraldehyde-3
      phosphate dehydrogenase B subunit of Arabidopsis thaliana.
AB  - The promoter of the nuclear gene, GAPB, which encodes the B subunit of
      chloroplast glyceraldehyde-3-phosphate dehydrogenase (GADPH) of Arabidopsis
      thaliana, was previously shown to contain four direct repeats (Gap boxes, located
      between -237 and -181) that were necessary but not sufficient for light-activated
      gene transcription. To identify additional elements located between the Gap boxes
      and TATA box, various GAPB promoter fragments driving the beta-glucuronidase
      (GUS) reporter gene were constructed in transgenic Arabidopsis. We found a 23 bp
      element (the XXIII element), centered at -119, that is essential for promoter
      activity. Mutations in the XXIII element abolished transcription of GAPB
      completely. Furthermore, we have identified three additional elements, PI,
      Tboxes, and PII that serve as positive modulators in the light-activated
      transcription of GAPB. Mutations in any of these three elements resulted in the
      reduction in light inducibility of the GAPB gene. The PI, XXIII, Tboxes and PII
      sequences are novel cis-acting elements that are not present in the closely
      related GAPA promoter or other promoters that are similarly regulated by light.
      In our current study, we found that transgenic Arabidopsis containing a GAPB
      promoter::GUS construct with all four Gap boxes deleted exhibited significant GUS
      expression albeit reduced to 42% of the optimal expression level. In contrast, in
      previous studies on transgenic tobacco, total abolishment of GUS expression was
      seen when the Gap boxes were deleted. This suggests that different trans-acting
      factors present in heterologous systems may result in variability of the
      expression of the transgene.

PMID- 11442055
TI  - NIMIN-1, NIMIN-2 and NIMIN-3, members of a novel family of proteins from
      Arabidopsis that interact with NPR1/NIM1, a key regulator of systemic acquired
      resistance in plants.
AB  - NPR1/NIM1 is a key regulator of systemic acquired resistance (SAR) in
      Arabidopsis. Using the yeast two-hybrid system, we have identified three novel
      genes, NIMIN-1, NIMIN-2 and NIMIN-3 (NIMIN for NIM1-interacting) that encode
      structurally related proteins interacting physically with NPR1/NIM1. NIMIN-1 and
      NIMIN-2 both bind strongly to NPR1/NIM1 via a common binding motif interacting
      with the C-terminal moiety of NPR1/NIM1, whereas NIMIN-3 interacts with NPR1/NIM1
      via the N-terminal part of NPR1/NIM1. In addition, NIMIN-1, NIMIN-2, and NIMIN-3
      are able to interact via NPR1/NIM1 with basic leucine zipper transcription
      factors of the TGA family in a yeast tri-hybrid system. A mutant protein of
      NPR1/NIM1, npr1-2, which has been shown to be severely impaired in induction of
      SAR gene expression, failed to bind the NIMIN proteins. The NIMIN genes are
      expressed in Arabidopsis plants in response to SAR-inducing treatments, and the
      NIMIN proteins, like NPR1/NIM1, carry functional nuclear localization signals as
      revealed by expression of fusion proteins in yeast and in transgenic plants.
      Taken together, these data indicate that the NIMIN proteins, via physical
      interaction with NPR1/NIM1, are part of the signal transduction pathway leading
      to SAR gene expression in Arabidopsis.

PMID- 11442056
TI  - Characterization of an ATP-dependent type I DNA ligase from Arabidopsis thaliana.
AB  - Here we report the purification and biochemical characterization of recombinant
      Arabidopsis thaliana DNA ligase I. We show that this ligase requires ATP as a
      source for adenylation. The calculated Km [ATP] for ligation is 3 microM. This
      enzyme is able to ligate nicks in oligo(dT)/poly(dA) and oligo(rA)/poly(dT)
      substrates, but not in oligo(dT)/poly(rA) substrates. Double-stranded DNAs with
      cohesive or blunt ends are also good substrates for the ligase. These biochemical
      features of the purified enzyme show the characteristics typical of a type I DNA
      ligase. Furthermore, this DNA ligase is able to perform the reverse reaction
      (relaxation of supercoiled DNA) in an AMP-dependent and PPi-stimulated manner.

PMID- 11442057
TI  - Site specificity of the Arabidopsis METI DNA methyltransferase demonstrated
      through hypermethylation of the superman locus.
AB  - Plants with low levels of DNA methylation show a range of developmental
      abnormalities including homeotic transformation of floral organs. Two independent
      DNA METHYLTRANSFERASEI (METI) antisense transformants with low levels of DNA
      methylation had flowers with increased numbers of stamens which resembled flowers
      seen on the loss-of-function superman (sup) mutant plants and on transgenic
      plants that ectopically express APETALA3 (AP3). These METI antisense plants have
      both increased and decreased methylation in and around the sup gene, compared
      with untransformed controls. DNA from the antisense plants was demethylated at
      least 4 kb upstream of the sup gene, while there was dense methylation around the
      start of transcription and within the coding region of this gene; these regions
      were unmethylated in control DNA. Methylation within the sup gene was correlated
      with an absence of SUP transcripts. The pattern and density of methylation was
      heterogeneous among different DNA molecules from the same plant, with some
      molecules being completely unmethylated. Methylcytosine occurred in asymmetric
      sites and in symmetric CpA/TpG but rarely in CpG dinucleotides in the antisense
      plants. In contrast, segregants lacking the METI antisense construct and
      epimutants with a hypermethylated allele of sup (clark kent 3), both of which
      have active METI genes, showed a higher frequency of methylation of CpG
      dinucleotides and of asymmetric cytosines. We conclude that METI is the
      predominant CpG methyltransferase and directly or indirectly affects asymmetric
      methylation.

PMID- 11442058
TI  - Pollen-specific regulation of vacuolar H+-PPase expression by multiple cis-acting
      elements.
AB  - We dissected the regulatory region of the AVP1 gene encoding the vacuolar H+
      pyrophosphatase (V-PPase) of Arabidopsis thaliana by using a GUS-reporter assay
      system. The cloned 1.4 kb 5'-regulatory region in the GUS-reporter transgenic
      plants was sufficient for the light-induced repression. Furthermore, the 1.4 kb
      regulatory region was active in all tissues examined and its activity was
      especially enhanced in pollen, whereas the shorter 0.4 kb regulatory region was
      active only in pollen. Further detailed analyses revealed that the GUS activity
      in pollen was regulated by at least three cis-acting regions in an additive or
      synergetic manner. These findings establish a distinct mechanism of the tissue
      specific regulation of V-PPase expression in developing pollen. and imply the
      biological significance of the V-PPase in pollen maturation.

PMID- 11442059
TI  - DNA binding mediated by the wheat HMGa protein: a novel instance of selectivity
      against alternating GC sequence.
AB  - The high-mobility-group (HMG) chromosomal protein wheat HMGa was purified to
      homogeneity and tested for its binding characteristics to double-stranded DNA.
      Wheat HMGa was able to bind to P268, an A/T-rich fragment derived from the pea
      plastocyanin gene promoter, producing a small mobility shift in gel retardation
      assays where the bound complex was sensitive to addition of proteinase K but
      resistant to heat treatment of the protein, consistent with the identity of wheat
      HMGa as a putative HMG-I/Y protein. Gel retardation assays and southwestern
      hybridization analysis revealed that wheat HMGa could selectively interact with
      the DNA polynucleotides poly(dA).poly(dT), poly(dAdT).poly(dAdT), and
      poly(dG).poly(dC), but not with poly(dGdC).poly(dGdC). Surface plasmon resonance
      analysis determined the kinetic and affinity constants of sensor chip-immobilized
      wheat HMGa for double-stranded DNA 10-mers, revealing a good affinity of the
      protein for various dinucleotide combinations, except that of alternating GC
      sequence. Thus contrary to prior reports of a selectivity of wheat HMGa for A/T
      rich DNA, the protein appears to be able to interact with sequences containing
      guanine and cytosine residues as well, except where G/C residues alternate
      directly in the primary sequence.

PMID- 11442060
TI  - An upstream region of the Arabidopsis thaliana CDKA;1 (CDC2aAt) gene directs
      transcription during trichome development.
AB  - The cell cycle of eukaryotes is tightly regulated through the activity of cyclin
      dependent kinases. The Arabidopsis thaliana CDKA;1 (CDC2aAt) gene is thought to
      encode such a protein kinase, since it is actively transcribed in proliferating
      tissues and can complement defects in the Schizosaccharomyces pombe cdc2 gene. We
      analyzed the functional structure of the CDKA;1 promoter, using fusion genes
      between various upstream regions of CDKA;1 and the Escherichia coli beta
      glucuronidase (GUS) gene. A 595 bp DNA fragment upstream from the transcription
      start site conferred GUS activity on developing trichomes, but not on
      proliferating tissues. On the other hand, another upstream fragment extending to
      the 5' non-coding transcribed region gave GUS activity to both proliferating
      tissues and developing trichomes. Against the gl2 mutant background, GUS activity
      directed by the 595 bp fragment was detected in single-stalk cells, but not in
      giant cells without obvious polar extension growth. These results revealed that
      the 595 bp fragment lacks cis element(s) essential for proliferating-cell
      specific promoter activity, but can direct transcription in a specific period
      during trichome development, which does not include cell division. This suggests
      that CDKA;1 functions during cell morphogenesis as well as cell proliferation.

PMID- 11442061
TI  - Early and multiple Ac transpositions in rice suitable for efficient insertional
      mutagenesis.
AB  - A GFP excision assay was developed to monitor the excision of Ac introduced into
      rice by Agrobacterium-mediated transformation. The presence of a strong double
      enhancer element of the CaMV 35S promoter adjacent to the Ac promoter induced
      very early excision, directly after transformation into the plant cell,
      exemplified by the absence of Ac in the T-DNA loci. Excision fingerprint analysis
      and characterization of transposition events from related regenerants revealed an
      inverse correlation between the number of excision events and transposed Ac
      copies, with single early excisions after transformation generating Ac
      amplification. New transpositions were generated at a frequency of 15-50% in
      different lines, yielding genotypes bearing multiple insertions, many of which
      were inherited in the progeny. The sequence of DNA flanking Ac in three
      representative lines provided a database of insertion tagged sites suitable for
      the identification of mutants of sequenced genes that can be examined for
      phenotypes in a reverse genetics strategy to elucidate gene function. Remarkably,
      two-thirds of Ac tagged sites showing homology to sequences in public databases
      were in predicted genes. A clear preference of transposon insertions in genes
      that are either predicted by protein coding capacity or by similarity to ESTs
      suggests that the efficiency of recovering knockout mutants of genes could be
      about three times higher than random. Linked Ac transposition, suitable for
      targeted tagging, was documented by segregation analysis of a crippled Ac element
      and by recovery of a set of six insertions in a contiguous sequence of 70 kb from
      chromosome 6 of rice.

PMID- 11442062
TI  - Functional characterization of beta-ketoacyl-CoA synthase genes from Brassica
      napus L.
AB  - Seed-specifically expressed beta-ketoacyl-CoA synthase genes of Brassica napus
      (Bn-FAE1.1 genes) were cloned from two cultivars, namely Askari, a high-erucic
      acid type, and Drakkar, a low-erucic-acid type. The genes from the two cultivars
      were found to be nearly identical. They encode proteins of 507 amino acids, the
      sequences of which differ only at position 282. The Bn-FAE1.1 gene of Askari,
      unlike that of Drakkar, was functionally expressed in yeast cells suggesting that
      the single amino acid exchange effects the low erucic acid phenotype at the E1
      gene locus. In yeast cells the beta-ketoacyl-CoA synthase of Askari elongated not
      only oleoyl but also palmitoleoyl groups as well as saturated acyl groups in such
      a way that monounsaturated acyl groups of 22 carbons and saturated ones of 26
      carbons were formed as main products. A reporter gene fused to the promoter
      region of the Bn-FAE1.1 gene from Askari showed seed-specific expression in
      transgenic rapeseed plants. Over-expression of the coding region of the Askari
      gene in developing seeds of transgenic Drakkar plants resulted in a significant
      increase in the levels of eicosenoic acid and erucic acid esterified in the seed
      oil. On the other hand, in transgenic high-erucic-acid rapeseed plants the
      increase in erucic acid level was at most 60% although the chimeric Bn-FAE1.1
      gene was co-expressed with an erucoyl-CoA-specific lysophosphatidate
      acyltransferase gene enabling trierucoyl glycerol to accumulate in the seed oil.

PMID- 11442064
TI  - Automatic generation of teaching files during routine clinical dictation.

PMID- 11442063
TI  - Three different genes encode the iron-sulfur subunit of succinate dehydrogenase
      in Arabidopsis thaliana.
AB  - The iron-sulfur protein is an essential component of mitochondrial complex II
      (succinate dehydrogenase, SDH), which is a functional enzyme of both the citric
      acid cycle and the respiratory electron transport chain. This protein is encoded
      by a single-copy nuclear gene in mammals and fungi and by a mitochondrial gene in
      Rhodophyta and the protist Reclinomonas americana. In Arabidopsis thaliana, the
      homologous protein is now found to be encoded by three nuclear genes. Two genes
      (sdh2-1 and sdh2-2) likely arose from a relatively recent duplication event since
      they have similar structures, encode nearly identical proteins and show similar
      expression patterns. Both genes are interrupted by a single intron located at a
      conserved position. Expression was detected in all tissues analysed, with the
      highest steady-state mRNA levels found in flowers and inflorescences. In
      contrast, the third gene (sdh2-3) is interrupted by 4 introns, is expressed at a
      low level, and encodes a SDH2-3 protein which is only 67% similar to SDH2-1 and
      SDH2-2 and has a different N-terminal presequence. Interestingly, the proteins
      encoded by these three genes are probably functional because they are highly
      conserved compared with their homologues in other organisms. These proteins
      contain the cysteine motifs involved in binding the three iron-sulfur clusters
      essential for electron transport. Furthermore, the three polypeptides are found
      to be imported into isolated plant mitochondria.

PMID- 11442065
TI  - Assessing portal design skills in the radiation oncology interactive case
      management examination.
AB  - The American Board of Radiology is developing a computerized interactive case
      management examination to be used to evaluate the clinical skills of radiation
      oncologists. In the past, these skills have been evaluated by a pencil and paper
      written examination and an oral examination. With the increasing capabilities of
      computers, these skills can be easily, and perhaps even better, evaluated
      digitally. The aim is to develop an examination, which will be based on actual
      clinical cases, and be interactive so that it better mimics the clinical practice
      of a radiation oncologist than a written examination. It will also be less labor
      intensive and less expensive than an oral examination. One of the most important
      skills of a radiation oncologist is the ability to design treatment portals that
      will encompass the entire cancer and yet minimize the irradiation of critical
      tissues and normal organs. Important parameters for radiation oncologists include
      the direction of the treatment beam, the size and shape of the portals, and the
      location of the margins of the field relative to patient anatomy and tumor
      location. In order to evaluate a physician's ability to design treatment portals,
      the computer-based examination has the capability to interactively construct
      field lines. The computer interface allows the candidate to draw field lines on a
      digitized x-ray image in a manner similar to practice. After the candidate
      illustrates the field lines, the evaluation of the response must be performed
      quickly to avoid interrupting the flow of the examination. The answer key is
      stored as a lossless compressed image. The key contains three regions consisting
      of (1) the must include region, which contains the tumor; (2) the must-exclude
      region, which contains tissues that if damaged would affect patient vitality and
      quality of life; and (3) the envelope of acceptable curves. Each region is
      assigned a unique byte code. The candidate's response is assigned a fourth byte
      code. Using basic logic operations, the response is swiftly evaluated. The
      scoring algorithm scores a candidate's action as correct if his/her drawn area
      encompasses all of the "must-include region" and is within the "envelope of
      acceptable curves." It scores a candidate's action as incorrect if his/her drawn
      area overlaps any part of the "exclude region" and/or exceeds at any point the
      "envelope of acceptable curves."

PMID- 11442066
TI  - Beyond the electronic textbook model: software techniques to make on-line
      educational content dynamic.
AB  - OBJECTIVE: We describe a working software technology that enables educators to
      incorporate their expertise and teaching style into highly interactive and
      Socratic educational material for distribution on the world wide web.
      MATERIALS/METHODS: A graphically oriented interactive authoring system was
      developed to enable the computer novice to create and store within a database his
      or her domain expertise in the form of electronic knowledge. The authoring system
      supports and facilitates the input and integration of several types of content,
      including free-form, stylized text, miniature and full-sized images, audio, and
      interactive questions with immediate feedback. The system enables the
      choreography and sequencing of these entities for display within a web page as
      well as the sequencing of entire web pages within a case-based or thematic
      presentation. Images or segments of text can be hyperlinked with point-and-click
      to other entities such as adjunctive web pages, audio, or other images, cases, or
      electronic chapters. Miniature (thumbnail) images are automatically linked to
      their full-sized counterparts. The authoring system contains a graphically
      oriented word processor, an image editor, and capabilities to automatically
      invoke and use external image-editing software such as Photoshop. The system
      works in both local area network (LAN) and internet-centric environments. An
      internal metalanguage (invisible to the author but stored with the content) was
      invented to represent the choreographic directives that specify the interactive
      delivery of the content on the world wide web. A database schema was developed to
      objectify and store both this electronic knowledge and its associated
      choreographic metalanguage. A database engine was combined with page-rendering
      algorithms in order to retrieve content from the database and deliver it on the
      web in a Socratic style, assess the recipient's current fund of knowledge, and
      provide immediate feedback, thus stimulating in-person interaction with a human
      expert. RESULTS: This technology enables the educator to choreograph a stylized,
      interactive delivery of his or her message using multimedia components assembled
      in virtually any order, spanning any number of web pages for a given case or
      theme. An educator can thus exercise precise influence on specific learning
      objectives, embody his or her personal teaching style within the content, and
      ultimately enhance its educational impact. CONCLUSION: The described technology
      amplifies the efforts of the educator and provides a more dynamic and enriching
      learning environment for web-based education.

PMID- 11442067
TI  - Empowering radiologic education on the Internet: a new virtual website technology
      for hosting interactive educational content on the World Wide Web.
AB  - OBJECTIVE: We describe a virtual web site hosting technology that enables
      educators in radiology to emblazon and make available for delivery on the world
      wide web their own interactive educational content, free from dependencies on in
      house resources and policies. MATERIALS/METHODS: This suite of technologies
      includes a graphically oriented software application, designed for the computer
      novice, to facilitate the input, storage, and management of domain expertise
      within a database system. The database stores this expertise as choreographed and
      interlinked multimedia entities including text, imagery, interactive questions,
      and audio. Case-based presentations or thematic lectures can be authored locally,
      previewed locally within a web browser, then uploaded at will as packaged
      knowledge objects to an educator's (or department's) personal web site housed
      within a virtual server architecture. This architecture can host an unlimited
      number of unique educational web sites for individuals or departments in need of
      such service. Each virtual site's content is stored within that site's protected
      back-end database connected to Internet Information Server (Microsoft Corp,
      Redmond WA) using a suite of Active Server Page (ASP) modules that incorporate
      Microsoft's Active Data Objects (ADO) technology. Each person's or department's
      electronic teaching material appears as an independent web site with different
      levels of access--controlled by a username-password strategy--for teachers and
      students. There is essentially no static hypertext markup language (HTML).
      Rather, all pages displayed for a given site are rendered dynamically from case
      based or thematic content that is fetched from that virtual site's database. The
      dynamically rendered HTML is displayed within a web browser in a Socratic fashion
      that can assess the recipient's current fund of knowledge while providing
      instantaneous user-specific feedback. Each site is emblazoned with the logo and
      identification of the participating institution. Individuals with teacher-level
      access can use a web browser to upload new content as well as manage content
      already stored on their virtual site. Each virtual site stores, collates, and
      scores participants' responses to the interactive questions posed on line.
      CONCLUSION: This virtual web site strategy empowers the educator with an end-to
      end solution for creating interactive educational content and hosting that
      content within the educator's personalized and protected educational site on the
      world wide web, thus providing a valuable outlet that can magnify the impact of
      his or her talents and contributions.

PMID- 11442068
TI  - "WWW.MDTF.ORG": a World Wide Web forum for developing open-architecture, freely
      distributed, digital teaching file software by participant consensus.
AB  - PURPOSE: To foster a community supported evaluation processes for open-source
      digital teaching file (DTF) development and maintenance. The mechanisms used to
      support this process will include standard web browsers, web servers, forum
      software, and custom additions to the forum software to potentially enable a
      mediated voting protocol. The web server will also serve as a focal point for
      beta and release software distribution, which is the desired end-goal of this
      process. CONCLUSIONS: We foresee that www.mdtf.org will provide for widespread
      distribution of open source DTF software that will include function and interface
      design decisions from community participation on the website forums.

PMID- 11442069
TI  - Integrating Digital Imaging and Communications in Medicine (DICOM)-structured
      reporting into the hospital environment.
AB  - The Digital Imaging and Communications in Medicine (DICOM) Standards Committee
      has balloted and accepted a new class of objects dealing with the generation,
      distribution, and management of reports. The structured reporting (SR) objects
      bridge the traditional separation between imaging and information systems. The
      DICOM SR objects offer a higher level of integration of the medical enterprise,
      providing practitioners with an effective tool to cover all aspects of the
      medical process from admission to discharge. This report presents the technical
      challenges posed by integrating the concepts introduced by SR with a complete
      hospital information system (HIS).

PMID- 11442070
TI  - Research and teaching access to a large clinical picture archiving and
      communication system.
AB  - PURPOSE: To identify practical issues surrounding delivering digital images from
      picture archiving and communication systems (PACS) for research and teaching
      purposes. The complexity of Digital Imaging and Communications in Medicine
      (DICOM) access methods, security, patient confidentiality, PACS database
      integrity, portability, and scalability are discussed. A software prototype
      designed to resolve these issues is described. SYSTEM ARCHITECTURE: A six
      component, three-tier, client server software application program supporting
      DICOM query/retrieve services was developed in the JAWA language. This software
      was interfaced to a large GE (Mt Prospect, IL) Medical Systems clinical PACS at
      Northwestern Memorial Hospital (NMH). CONCLUSION: Images can be delivered from a
      clinical PACS for research and teaching purposes. Concerns for security, patient
      confidentiality, integrity of the PACS database, and management of the
      transactions can be addressed. The described software is one such solution for
      achieving this goal.

PMID- 11442071
TI  - Electronic teaching files: seven-year experience using a commercial picture
      archiving and communication system.
AB  - With the advent of electronic imaging and the internet, the ability to create,
      search, access, and archive digital imaging teaching files has dramatically
      improved. Despite the fact that a picture archival and communication system
      (PACS) has the potential to greatly simplify the creation of, archival, and
      access to a department or multifacility teaching file, this potential has not yet
      been satisfactorily realized in our own and most other PACS installations.
      Several limitations of the teaching file tools within our PACS have become
      apparent over time. These have, at our facility, resulted in a substantially
      reduced role of the teaching file tools for conferences, daily teaching, and
      research purposes. With the PACS at our institution, academic folders can only be
      created by the systems engineer, which often serves as an impediment to the
      teaching process. Once these folders are created, multiple steps are required to
      identify the appropriate folders, and subsequently save images. Difficulties
      exist for those attempting to search for the teaching file images. Without pre
      existing knowledge of the folder name and contents, it is difficult to query the
      system for specific images. This is due to the fact that there is currently no
      fully satisfactory mechanism for categorizing, indexing, and searching cases
      using the PACS. There is currently no easy mechanism to save teaching, research,
      or clinical files onto a CD or other removable media or to automatically strip
      demographic or other patient information from the images. PACS vendors should
      provide much more sophisticated tools to create and annotate teaching file images
      in an easy to use but standard format (possibly Radiological Society of North
      America's Medical Image Resource Center [MIRC] format) that could be exchanged
      with other sites and other vendors' PAC systems. The privilege to create teaching
      or conference files should be given to the individual radiologists,
      technologists, and other users, and an audit should be kept of who has created
      these files, as well as keep track of who has accessed the files. Vendors should
      maintain a local PACS library of image quality phantoms, normal variants, and
      interesting cases and should have the capability of accessing central image
      repositories such as the RSNA's MIRC images. Commercial PAC systems should
      utilize a standard lexicon to facilitate the creation and categorization of
      images, as well as to facilitate sharing of images and related text with other
      sites. This should be combined with a very easy to use mechanism to write images
      and related text when appropriate onto removable media (while maintaining a high
      level of security and confidentiality) to make it easier to share images for
      teaching, research, or clinical purposes.

PMID- 11442072
TI  - Digital radiography and film scanners: automating the transition to filmless
      radiology.
AB  - To facilitate the integration of digital radiography (DR) and legacy film/screen
      technology, we have devised a methodology for film digitization that optimizes
      workflow and integrates well with the picture archiving and communication system
      (PACS). This work was performed at Mercy Medical Center (Cedar Rapids, IA) using
      a film digitizer with built-in Digital Imaging and Communications in Medicine
      (DICOM) communication. The radiology department at Mercy has one DR system and
      three separate film/screen systems. The DR system software suite features DICOM
      Modality Worklist capability to provide complete radiology information system
      (RIS) integration functionality. This provides for patient demographic
      information to be automatically downloaded from the RIS worklist to populate the
      DICOM image header. Likewise, we have taken advantage of the film scanner's DICOM
      capability to develop software linking it with the hospital RIS. This capability
      provides a worklist downloading functionality equivalent to that of the DR.
      Patient demographics can then be rapidly downloaded as each film is digitized.
      The worklist capability of the scanner is essential in several respects. First,
      it guarantees that patient demographic information is completely accurate and,
      therefore, that the digitized x-ray image will be merged with the correct patient
      file in the PACS. Additionally, high film scanner throughput is achieved,
      guaranteeing that all inpatient-digitized films are as readily available on the
      PACS as their DR image counterparts. The digitized images have proven to be of
      diagnostic quality on the typical 1K by 1K PACS workstation. Also, as patients
      are admitted to the hospital, prior films from the radiology archive are
      digitized to form a readily available patient history for in-house physicians.
      Over time, we are building archival patient histories of soft-copy images that
      will enable increased availability of patient x-rays to both in-hospital and
      outside referring physicians, especially as more internet-viewing software
      becomes available to the out-of-hospital medical community. Finally, the results
      of this study show that high-throughput RIS integration of film scanning
      equipment is a key component to making a graceful transition to the filmless
      hospital as more DR systems are installed.

PMID- 11442073
TI  - An academic radiology information system (RIS): a review of the commercial RIS
      systems, and how an individualized academic RIS can be created and utilized.
AB  - Current commercial radiology information systems (RIS) are designed for
      scheduling, billing, charge collection, and report dissemination. Academic
      institutions have additional requirements for their missions for teaching,
      research and clinical care. The newest versions of commercial RIS offer greater
      flexibility than prior systems. We sent questionnaires to Cerner Corporation,
      ADAC Health Care Information Systems, IDX Systems, Per-Se' Technologies, and
      Siemens Health Services regarding features of their products. All of the products
      we surveyed offer user customizable fields. However, most products did not allow
      the user to expand their product's data table. The search capabilities of the
      products varied. All of the products supported the Health Level 7 (HL-7)
      interface and the use of structured query language (SQL). All of the products
      were offered with an SQL editor for creating customized queries and custom
      reports. All products included capabilities for collecting data for quality
      assurance and included capabilities for tracking "interesting cases," though they
      varied in the functionality offered. No product offered dedicated functions for
      research. Alternatively, radiology departments can create their own client-server
      Windows-based database systems to supplement the capabilities of commercial
      systems. Such systems can be developed with "web-enabled" database products like
      Microsoft Access or Apple Filemaker Pro.

PMID- 11442074
TI  - Automating clinically relevant prefetch processes in picture archiving and
      communication systems solutions.
AB  - As picture archiving and communication systems (PACS) hit the mainstream of
      projects gaining attention and priority in healthcare organizations, the promise
      of achieving better operational efficiencies in the radiology department is at
      the forefront of the financing discussions. Although some positive economic
      returns have been documented from the early proponents of PACS, most of the PACS
      installations are still working through operational changes in regards to digital
      image prefetching to achieve this objective. The lynchpin for achieving the
      desired operational efficiency is the enabling of an automated, clinically
      relevant prefetch process for comparison studies from the digital archives. This
      report explores the solutions deployed at two hospital systems in Minneapolis to
      utilize a "comparative region of interest" data element to augment the body
      region information typically available for prefetching in the PACS system. With
      this information, the prospective PACS implementer will know how to build in
      their body region requirements up-front in order to maximize their operational
      efficiency benefits later.

PMID- 11442075
TI  - Support of clinician image-related workflow by a user-edited, web-based patient
      list manager.
AB  - Clinician efficiency can be enhanced by worklists that compile useful data for
      rapid access at the time of need. The authors report development of a web-based,
      user-edited "Patient List Manager" for the Clinical Image Management System
      (CIMS). The CIMS List Manager interfaces with the CIMS Archive to provide the
      user with available studies. It has tools that let the user build personal lists
      from the available studies. Listed studies are moved from the archive to the
      cache for rapid access at the time of need. Users can build/edit the list through
      a browser (without viewing pictures) or from within the image viewer. In this
      way, the List Manager distributes list building into knowledgeable hands. This is
      particularly valuable at the current time when health system patient registries
      are not mature enough to reliably support building build anticipatory patient
      lists.

PMID- 11442076
TI  - Automated examination notification of emergency department images in a picture
      archiving and communication system.
AB  - This study compares the timeliness of radiology interpretation of Emergency
      Department (ED) imaging examinations in a picture archiving and communication
      system (PACS) before and after implementation of an automated paging system for
      notification of image availability. An alphanumeric pager for each radiology
      subspecialty (chest, pediatrics, bone, neuroradiology, and body) was used to
      alert the responsible radiologist that an ED imaging examination is available to
      be viewed on the PACS. The paging system was programmed to trigger off of the
      PACS database when an image is received on the appropriate radiology display
      station. The pager message includes the radiology accession number and
      examination description (such as chest, two-view, or c-spine, etc). The PACS
      paging tool performance was assessed by calculating the time elapsed, for each ED
      imaging examination, from the Time Imaged to the Time of Interpretation, where
      the Time Imaged is the actual image completion time measured at the imaging
      modality, and the Time Interpreted is the time a radiology interpretation is
      rendered to the ED, and is measured from the Radiology-to-ED fax time stamp.
      These measures were analyzed pre- and post-paging system implementation to
      determine any impact of the automated notification tool on radiology service
      turnaround time. Results show an improved radiology response time from image
      completion to interpretation rendered to ED clinicians, down from hour(s) to
      minutes, with the automated paging examination notification system. Examinations
      are read by the appropriate radiology specialty section in a more timely fashion,
      and fewer cases go unread by radiology.

PMID- 11442077
TI  - Distance learning in the digital environment.
AB  - The expansion of radiology departments and divisions often can not occur in
      adjacent geographic locations. This leads to a greater separation of staff and
      residents, as well as workers in similar divisions. This makes traditional
      teaching difficult in academic institutions. The economic drive forcing many
      departments to investigate more isolated outpatient imaging centers has further
      hindered the ability to continue effective academic training at many facilities.
      The ability to easily share a digital environment across physical distance can
      greatly enhance the teaching experience, as well as be a valuable tool for
      consultation and case discussion with referring clinicians. The transition to a
      filmless environment with picture archiving and communication systems (PACS) can
      be utilized for distance learning in addition to the clinical arena. It is
      possible to take advantage of the digital transformation to PACS and case-viewing
      browser programs to conduct improved interactions with referring clinicians as
      well as radiologic teaching with relatively minimal hardware and software
      demands. The integration of web-based teleradiology programs with business
      networking software can be used for effective distance learning in the digital
      environment, sufficiently closing the distance on our rapidly expanding
      departments. This same technology allows for greater interaction with referring
      clinicians for real-time consultation and enhanced case discussion to entrench a
      supportive referral base for the radiologic community.

PMID- 11442078
TI  - Using digital certificates for radiology result receipt confirmation.

PMID- 11442079
TI  - Functional requirements of a desktop clinical image display application.

PMID- 11442080
TI  - Minimizing Digital Imaging and Communications in Medicine (DICOM) Modality
      Worklist patient/study selection errors.
AB  - Frequently when patient and study identification information (patient name,
      patient identification, date of birth, sex, and accession number) are manually
      entered at a modality, typographical errors occur that have to be corrected
      before the acquired images can be matched to the proper patient and study on a
      picture archiving and communication system (PACS). The Digital Imaging and
      Communication in Medicine (DICOM) Modality Worklist service alleviates these
      problems by automatically transferring this data from the radiology information
      system (RIS) to the image acquisition modality. The technologist then does not
      have to manually re-enter the data to place it into the image files. With
      modality worklist, precise patient and study data are obtained and placed into
      the image headers with no typographical errors. When the images are sent to the
      PACS, they match the corresponding patient and study records, and are immediately
      incorporated into the electronic patient record. While modality worklist does
      replace the manual keying of the data and virtually eliminates typographical
      problems, it introduces a new source of human error: the incorrect selection of
      the patient and/or study from the computerized worklist, and the resultant
      mislabeling of the images. When these mislabeled images are sent to the PACS,
      they are immediately associated with the wrong patient and/or study, where they
      potentially may cause serious harm. The goal of this report is to raise awareness
      to this problem, to identify the major causes of these errors, and to offer some
      practical suggestions on how to minimize them.

PMID- 11442081
TI  - A web implementation: the good and the not-so-good.
AB  - E-commerce, e-mail, e-greeting, e-this, and e-that everywhere you turn there is a
      new "e" word for an internet or Web application. We, at the Cleveland Clinic
      Foundation, have been "e-nlightened" and will discuss in this report the
      implementation of a web-based radiology information system (RIS) in our radiology
      division or "e-radiology" division. The application, IDXRad Version 10.0 from IDX
      Corp, Burlington, VT, is in use at the Cleveland Clinic Foundation and has both
      intranet (for use in Radiology) and internet (referring physician viewing)
      modules. We will concentrate on the features of using a web browser for the
      application's front-end, including easy prototyping for screen review, easier
      mock-ups of demonstrations by vendors and developers, and easier training as more
      people become web-addicted. Project communication can be facilitated with an
      internal project web page, and use of the web browser can accommodate quicker
      turnaround of software upgrades as the software code is centrally located.
      Compared with other technologies, including client/server, there is a smaller
      roll out cost when using a standard web browser. However, the new technology
      requires a change and changes are never implemented without challenges. A
      seasoned technologist using a legacy system can enter data quicker using function
      keys than using a graphical user interface and pointing and clicking through a
      series of pop-up windows. Also, effective use of a web browser depends on
      intuitive design for it to be easily implemented and accepted by the user. Some
      software packages will not work on both of the popular web browsers and then are
      tailored to specific release levels. As computer-based patient records become a
      standard, patient confidentiality must be enforced. The technical design and
      application security features that support the web-based software package will be
      discussed. Also web technologies have their own implementation issues.

PMID- 11442082
TI  - Picture archiving and communications systems (PACS) in private practice: St. Paul
      Radiology PACS project.
AB  - While much of diagnostic radiology is practiced in a private setting, many of the
      papers and presentations describing picture archiving and communications systems
      (PACS) implementation to date have been sponsored by university and government
      health facilities. We will present a 4-year retrospective review of a private
      practice PACS project. The challenges, benefits, and cost analysis of the PACS
      project will be presented.

PMID- 11442083
TI  - The Legnano radiology picture archiving and communication system/radiology
      information system project implementation.
AB  - The necessity to meet the ever-increasing diagnostic and interventional demands
      in the most cost-effective and efficient way led to the decision to turn the
      Department of Radiology at Legnano City Hospital nearly filmless. Crucial for the
      implementation of this challenging project was the development of a sophisticated
      and efficient digital architecture along with a nearly global renovation of the
      whole department, connecting it in the meantime to the hospital asynchronous
      transfer mode (ATM) backbone. The highlights and drawbacks faced in the
      implementation of the project are described and discussed.

PMID- 11442084
TI  - Trials and tribulations in deploying digital imaging network and picture
      archiving and communication system--film to filmless in 80 days.
AB  - The Naval Medical Center Portsmouth (NMCP) was constructed with the intention of
      deploying a picture archiving and communications system (PACS). All necessary
      infrastructures were installed and considerable planning was done during
      construction with the belief that this would make the deployment of the PACS much
      simpler. This was true during the early deployment; however, as time passed and
      the system was more heavily used, significant problems arose. User/operator
      related and hardware/software-related problems were encountered. Although, most
      have been corrected, some have persisted and will require considerable manpower
      and/or fiscal resources to correct. The lesson learned is that no matter how much
      preparation is done for deploying PACS, many significant problems will surface as
      the system is used that will require the continued attention of the deployment
      project officer.

PMID- 11442085
TI  - Tools to manage the enterprise-wide picture archiving and communications system
      environment.
AB  - The presentation will focus on the implementation and utilization of a central
      picture archiving and communications system (PACS) network-monitoring tool that
      allows for enterprise-wide operations management and support of the image
      distribution network. The MagicWatch (Siemens, Iselin, NJ) PACS/radiology
      information system (RIS) monitoring station from Siemens has allowed our
      organization to create a service support structure that has given us proactive
      control of our environment and has allowed us to meet the service level
      performance expectations of the users. The Radiology Help Desk has used the
      MagicWatch PACS monitoring station as an applications support tool that has
      allowed the group to monitor network activity and individual systems performance
      at each node. Fast and timely recognition of the effects of single events within
      the PACS/RIS environment has allowed the group to proactively recognize possible
      performance issues and resolve problems. The PACS/operations group performs
      network management control, image storage management, and software distribution
      management from a single, central point in the enterprise. The MagicWatch station
      allows for the complete automation of software distribution, installation, and
      configuration process across all the nodes in the system. The tool has allowed
      for the standardization of the workstations and provides a central configuration
      control for the establishment and maintenance of the system standards. This
      report will describe the PACS management and operation prior to the
      implementation of the MagicWatch PACS monitoring station and will highlight the
      operational benefits of a centralized network and system-monitoring tool.

PMID- 11442086
TI  - The process of transitioning to digital operations in a clinic setting.
AB  - Transitioning to digital imaging operations in a department of radiology is often
      difficult for many radiologists, but it is a change that many have made
      effectively. Transitioning to digital operations in a clinic setting is even more
      difficult for the referring physician operating a business in the clinic. This
      paper will discuss our experience with transitioning several off site clinics to
      digital imaging operations. We will discuss the process followed to identify the
      physical equipment required to support clinic operations in a digital imaging
      environment, the process followed to help the physicians adjust their work
      patterns to allow them to practice in a digital imaging environment, and the
      benefits and pitfalls of implementing digital imaging in an off site clinic. Four
      off site clinic locations will be evaluated: 1. cancer clinic located immediately
      adjacent to the main hospital that relies heavily on CT and MRI images in their
      practice, 2. small clinic located about 60 miles from the main hospital that
      acquires xray images on site, 3. larger clinic located about 20 miles from the
      main hospital that acquires xray, MRI and CT images on site, 4. sports medicine
      clinic located about 2 miles from the main hospital that acquires xray images on
      site. Each of these clinics has a very different patient clientele and therefore
      operates differently in nearly all aspects of their daily operations. The
      physician's need for and use of film and digital images varies significantly
      between the sites and therefore each site has presented different challenges to
      our implementation process. As we explain the decisions that were made for each
      of these sites and reveal the methods that were used to help the physicians make
      the transition, the readers should be able to draw information that will be
      helpful to them as they make their own transition to a digital operation.

PMID- 11442087
TI  - Image distribution in a multi-facility radiology practice.
AB  - The Cleveland Clinic Health System is a multifacility practice that distributes
      images electronically. Issues specific to the internal department at the main
      campus must be addressed with regard to the overall commitment to the healthcare
      system. Training for new and old employees on diagnostic and transcription
      equipment is a key issue. Interfacing different systems or different
      configurations of a system, either hospital or radiology information systems, is
      many times difficult and sometimes insurmountable. Issues of confidentiality have
      been addressed. In light of the impending new regulations from the Health
      Insurance Portability and Accountability Act, are the current system security
      practices enough?

PMID- 11442088
TI  - The National Institutes of Health Clinical Center Digital Imaging Network,
      Picture Archival and Communication System, and Radiology Information System.
AB  - In this work, we describe the digital imaging network (DIN), picture archival and
      communication system (PACS), and radiology information system (RIS) currently
      being implemented at the Clinical Center, National Institutes of Health (NIH).
      These systems are presently in clinical operation. The DIN is a redundant meshed
      network designed to address gigabit density and expected high bandwidth
      requirements for image transfer and server aggregation. The PACS projected
      workload is 5.0 TB of new imaging data per year. Its architecture consists of a
      central, high-throughput Digital Imaging and Communications in Medicine (DICOM)
      data repository and distributed redundant array of inexpensive disks (RAID)
      servers employing fiber-channel technology for immediate delivery of imaging
      data. On demand distribution of images and reports to clinicians and researchers
      is accomplished via a clustered web server. The RIS follows a client-server model
      and provides tools to order exams, schedule resources, retrieve and review
      results, and generate management reports. The RIS-hospital information system
      (HIS) interfaces include admissions, discharges, and transfers
      (ATDs)/demographics, orders, appointment notifications, doctors update, and
      results.

PMID- 11442089
TI  - Combining speech recognition software with Digital Imaging and Communications in
      Medicine (DICOM) workstation software on a Microsoft Windows platform.
AB  - This presentation describes our experience in combining speech recognition
      software, clinical review software, and other software products on a single
      computer. Different processor speeds, random access memory (RAM), and computer
      costs were evaluated. We found that combining continuous speech recognition
      software with Digital Imaging and Communications in Medicine (DICOM) workstation
      software on the same platform is feasible and can lead to substantial savings of
      hardware cost. This combination optimizes use of limited workspace and can
      improve radiology workflow.

PMID- 11442090
TI  - A study for watermark methods appropriate to medical images.
AB  - The network system, including the picture archiving and communication system
      (PACS), is essential in hospital and medical imaging fields these days. Many
      medical images are accessed and processed on the web, as well as in PACS.
      Therefore, any possible accidents caused by the illegal modification of medical
      images must be prevented. Digital image watermark techniques have been proposed
      as a method to protect against illegal copying or modification of copyrighted
      material. Invisible signatures made by a digital image watermarking technique can
      be a solution to these problems. However, medical images have some different
      characteristics from normal digital images in that one must not corrupt the
      information contained in the original medical images. In this study, we suggest
      modified watermark methods appropriate for medical image processing and
      communication system that prevent clinically important data contained in original
      images from being corrupted.

PMID- 11442091
TI  - A simple mechanism for sharing and transporting medical digital case information
      across disparate computer language and data storage environments.
AB  - It is challenging to remotely share generic medical case information without an
      agreed upon definition of a medical digital teaching file (DTF). By utilizing an
      application of the extensible markup language (XML) called web-distributed data
      exchange (WDDX) along with an agreed upon WDDX structure, it is technically easy
      to share or syndicate medical case DTFs across computing environments that use
      different information models and computer languages. Thus, this easily
      implemented technology offers us an immediately available means to share and
      increase the value of scientific knowledge.

PMID- 11442092
TI  - The Digital Imaging and Communications in Medicine (DICOM) archive is a dynamic
      component of a clinician image-related workflow solution.
AB  - The authors investigated clinician transactions against the Digital Imaging and
      Communications in Medicine (DICOM) archive within a clinical image management
      system (CIMS) in support of patient care. A Neurosurgical Oncology practice was
      audited for image utilization. There were 400 requests for 233 image studies
      during 297 sessions. Fifty percent were for current studies, and 50% were for
      historical studies. Current studies alone were requested in 37% of the sessions,
      current plus historical in 31%, and historical alone in 32% of the sessions.
      Seventy percent of studies were within 8 weeks old and were rapidly available
      from the CIMS disk cache without an archive image transaction. Conversely, 30%
      were older than 8 weeks, requiring a clinician transaction against the archive
      for image retrieval. Approximately 25% of studies were older than 3 months and
      10% older than 6 months. Clinician image needs are complex and any CIMS solution
      must include a DICOM archive that can support clinician-based transactions.

PMID- 11442093
TI  - Activity-based costing via an information system: an application created for a
      breast imaging center.
AB  - Activity-based costing (ABC) is a process that enables the estimation of the cost
      of producing a product or service. More accurate than traditional charge-based
      approaches, it emphasizes analysis of processes, and more specific identification
      of both direct and indirect costs. This accuracy is essential in today's
      healthcare environment, in which managed care organizations necessitate
      responsible and accountable costing. However, to be successfully utilized, it
      requires time, effort, expertise, and support. Data collection can be tedious and
      expensive. By integrating ABC with information management (IM) and systems (IS),
      organizations can take advantage of the process orientation of both, extend and
      improve ABC, and decrease resource utilization for ABC projects. In our case
      study, we have examined the process of a multidisciplinary breast center. We have
      mapped the constituent activities and established cost drivers. This information
      has been structured and included in our information system database for
      subsequent analysis.

PMID- 11442094
TI  - Conceptual database modeling: a method for enabling end users (radiologists) to
      understand and develop their information management applications.
AB  - As medical technology advances at a rapid pace, clinicians become further and
      further removed from the design of their own technological tools. This is
      particularly evident with information management. For radiologists, clinical
      histories, patient reports, and other pertinent information require sophisticated
      tools for data handling. However, as databases grow more powerful and
      sophisticated, systems require the expertise of programmers and information
      technology personnel. The radiologist, the clinician end-user, must maintain
      involvement in the development of system tools to insure effective information
      management. Conceptual database modeling is a design method that serves to bridge
      the gap between the technological aspects of information management and its
      clinical applications. Conceptual database modeling involves developing
      information systems in simple language so that anyone can have input into the
      overall design. This presentation describes conceptual database modeling, using
      object role modeling, as a means by which end-users (clinicians) may participate
      in database development.

PMID- 11442095
TI  - Creation of a software application for the clinical radiologist.
AB  - PURPOSE: To create a software application that automates a significant portion of
      a clinical radiologist's work. METHODS: The daily workflow of clinical
      radiologists in a university-based department was analyzed, specifically looking
      for manual tasks that could be implemented in software. An application that a
      practicing radiologist would use in his daily work was created. RESULTS: By using
      speech recognition, reports could be created, edited, and verified immediately.
      Online medical reference information could be made instantly accessible. Billing
      data could be captured accurately and completely at report creation time. A
      radiologist could be alerted to important upcoming events by use of a reminder
      system. Reports could be delivered immediately to referring physicians using
      either the internet or telephone. CONCLUSIONS: It is possible to improve the
      productivity of busy practicing clinical radiologists by automating a large
      portion of their workflow and implementing it in an easily mastered software
      application.

PMID- 11442096
TI  - Impact of a diagnostic workstation on workflow in the emergency department at a
      level I trauma center.
AB  - PURPOSE: When a computed tomography (CT) scan on a patient from the emergency
      department is completed at University of Medicine and Dentistry of New Jersey
      (UMDNJ)-University Hospital, a non-picture archiving and communication system
      (PACS) environment, formal diagnostic review cannot begin until the images are
      printed and transported to the on-call radiology resident. The time to reach a
      final diagnosis has been significantly reduced by the introduction of a single
      workstation in the on-call reading room. MATERIALS AND METHODS: Five radiology
      residents were studied. Each read 10 CT studies on film and 10 on a workstation.
      After a training period to familiarize the residents with the workstation,
      measurements were taken of the time required to read the examination and the time
      required for printing and transporting or networking the images. RESULTS: The
      average time required to transmit the images was reduced from approximately 40
      minutes to 16 minutes. Interpretation times between the workstation and film were
      comparable. CONCLUSION: The addition of a single workstation significantly
      reduces the time required to reach a final diagnosis by obviating the need to
      print and transport the images to the on-call radiology resident. Such time
      savings can have a significant impact on the care of trauma patients.

PMID- 11442097
TI  - Real-time volume rendering of four-dimensional images based on three-dimensional
      texture mapping.
AB  - A four-dimensional (4-D) image consists of three-dimensional (3-D) volume data
      that varies with time. It is used to express a deforming or moving object in
      virtual surgery or 4-D ultrasound. It is difficult to obtain 4-D images by
      conventional ray-casting or shear-warp factorization methods because of their
      time-consuming rendering process and the pre-processing stage necessary whenever
      the volume data are changed. Even when 3-D texture mapping is used, repeated
      volume loading is time-consuming in 4-D image rendering. In this study, we
      propose a method to reduce data loading time using coherence between currently
      loaded volume and previously loaded volume in order to achieve real-time
      rendering based on 3-D texture mapping. Volume data are divided into small bricks
      and each brick being loaded is tested for similarity to one that was already
      loaded in memory. If the brick passes the test, it is defined as 3-D texture by
      OpenGL functions. Later, the texture slices of the brick are mapped into polygons
      and blended by OpenGL blending functions. All bricks undergo this test. Using
      continuous deforming, 50 volumes are rendered in interactive time with SGI ONYX.
      Realtime volume rendering based on 3-D texture mapping is currently available for
      personal computers.

PMID- 11442098
TI  - Gradation processing algorithm of digital radiological chest image.
AB  - Gradation processing technology can enhance display contrast of interested region
      by using linear or nonlinear transform. Current algorithms generally calculate
      transform parameters depended on experimental statistical values or some simple
      image processing method such as histogram analysis. They cannot accord with the
      human subjective vision mechanism nor can they intelligently acquire required
      parameters. Therefore, processing results are not very accurate or reliable. We
      propose a gradation processing algorithm of digital radiological chest images
      based on region growing segmentation technology. It combines self-adapted
      segmentation with prior knowledge of directed segmentation, and its computation
      cost is low. It can perform contrast enhancement of the interested regions more
      accurately, and accords with the human subjective vision mechanism better.

PMID- 11442099
TI  - Comparative analysis of texture characteristics of malignant and benign tumors in
      breast ultrasonograms.
AB  - We evaluated various texture features and region of interest (ROI) types of
      breast ultrasonograms in order to determine the best-performing combinations for
      differentiating between benign and malignant solid breast nodules. A total of 21
      breast ultrasonograms (12 benign, nine malignant) containing solid breast nodules
      were evaluated. Eight ROI types were defined around the nodules. The texture
      feature of each ROI was measured and the ratios of texture features were
      calculated for each pair of ROIs. This procedure was repeated for five different
      feature types, thus yielding texture feature ratios for 140 different
      combinations of ROIs and texture features. We evaluated the performance of the
      texture feature ratio in differentiating between benign and malignant nodules
      using t test analysis. Evaluating the top ranked texture and ROI combinations, we
      found edge density and mutual information were the best two texture features, and
      that the ROI types of outside lesion and lesion margin had good performance.

PMID- 11442100
TI  - Segmentation by evolution for visualization of the lower extremity of the Visible
      Man.
AB  - Medical image segmentation is the crucial process for three-dimensional (3D)
      modeling. Many studies have claimed to suggest more accurate ways of
      segmentation. However, such research seems to have the drawback that it works
      against the parsimony principle. These methods have to resegment the regions of
      interest (ROIs) for the already segmented data, without taking advantage of the
      vast amount of past segmentation results. The present report proposes a
      "segmentation by evolution" method. It is an advanced segmentation paradigm that
      incorporates the existing segmentation results. The "segmentation by evolution"
      paradigm was applied to the color images of the Visible Human data.

PMID- 11442101
TI  - Using rigid motion constraints for the registration of free-form surfaces.
AB  - We present a new method for registration of freeform surfaces based on the
      iterative closest point (ICP) method and on geometric properties of reflected
      correspondence vectors. The method is based on computing relative gaps between
      reflected correspondences and between the projections of reflected
      correspondences along the rotation axis and using these to eliminate false
      matches. Experimental results on synthetic data and on real range images
      demonstrate that the method is robust and accurate for image registration with
      small motions.

PMID- 11442102
TI  - Comparisons of different contrast resolution effects on a computer-aided
      detection system intended to cluster microcalcifications detected in dense breast
      images.
AB  - Clustered microcalcifications, which are frequently an important signal of
      possible cancer, are usually hidden in dense breast images, adding more
      difficulty in mammogram medical analysis. In this work we evaluate the
      performance of a previously developed computer-aided detection scheme, modified
      for application to dense breast images. The main focus of this investigation was
      on the effect of different contrast resolutions on the processing performance. We
      have processed dense breast images digitized with 8 and 12 bits to evaluate the
      performance of this computer-aided detection scheme with different contrast
      resolutions. As expected, for most of the 12-bit images, the number of detected
      signals was greater or at least equal to that of the 8-bit images.

PMID- 11442103
TI  - Quality-control issues on high-resolution diagnostic monitors.
AB  - Previous literature indicates a need for more data collection in the area of
      quality control of high-resolution diagnostic monitors. Throughout acceptance
      testing, which began in June 2000, stability of monitor calibration was analyzed.
      Although image quality on all monitors was found to be acceptable upon initial
      acceptance testing using VeriLUM software by Image Smiths, Inc (Germantown, MD),
      it was determined to be unacceptable during the clinical phase of acceptance
      testing. High-resolution monitors were evaluated for quality assurance on a
      weekly basis from installation through acceptance testing and beyond. During
      clinical utilization determination (CUD), monitor calibration was identified as a
      problem and the manufacturer returned and recalibrated all workstations. From
      that time through final acceptance testing, high-resolution monitor calibration
      and monitor failure rate remained a problem. The monitor vendor then returned to
      the site to address these areas. Monitor defocus was still noticeable and
      calibration checks were increased to three times per week. White and black level
      drift on medium-resolution monitors had been attributed to raster size settings.
      Measurements of white and black level at several different size settings were
      taken to determine the effect of size on white and black level settings. Black
      level remained steady with size change. White level appeared to increase by 2.0
      cd/m2 for every 0.1 inches decrease in horizontal raster size. This was
      determined not to be the cause of the observed brightness drift. Frequency of
      calibration/testing is an issue in a clinical environment. The increased
      frequency required at our site cannot be sustained. The medical physics division
      cannot provide dedicated personnel to conduct the quality-assurance testing on
      all monitors at this interval due to other physics commitments throughout the
      hospital. Monitor access is also an issue due to radiologists' need to read
      images. Some workstations are in use 7 AM to 11 PM daily. An appropriate monitor
      calibration frequency must be established during acceptance testing to ensure
      unacceptable drift is not masked by excessive calibration frequency. Standards
      for acceptable black level and white level drift also need to be determined. The
      monitor vendor and hospital staff agree that currently, very small printed text
      is an acceptable method of determining monitor blur, however, a better method of
      determining monitor blur is being pursued. Although monitors may show acceptable
      quality during initial acceptance testing, they need to show sustained quality
      during the clinical acceptance-testing phase. Defocus, black level, and white
      level are image quality concerns, which need to be evaluated during the clinical
      phase of acceptance testing. Image quality deficiencies can have a negative
      impact on patient care and raise serious medical-legal concerns. The attention to
      quality control required of the hospital staff needs to be realistic and not have
      a significant impact on radiology workflow.

PMID- 11442104
TI  - Characterization of artifact simulating aortic dissection in computed tomography
      imaging.
AB  - An artifact simulating aortic dissection has been seen in computed tomography
      (CT) and reported in numerous journals. The purpose of this study is to determine
      the origin. A phantom was constructed to simulate the motion of the ascending
      aorta during the cardiac cycle. Technique factors such as scan time, slice
      thickness, pitch, and reconstruction algorithms were examined for their effect on
      the simulated dissection appearance. Change in the angle of the simulated aorta
      with respect to the scanner axis was also studied. CT images displaying the
      simulated aortic dissection are obtained reproducibly. The amplitude of the
      artifact is more pronounced for increased scan time. The artifact amplitude is
      proportional to the displacement of the phantom. The simulated aortic dissection
      seems to be more pronounced when the scan time is comparable to the cycling time
      of aortic motion.

PMID- 11442105
TI  - Use of a low-cost, PC-based image review workstation at a radiology department.
AB  - Despite the increasing use of diagnostic workstations, film reading is still
      commonplace in most radiology departments all over the world. The purpose of this
      work is to assess the adoption of image review workstations in a radiology
      department where the usual primary diagnosis is film-based and cannot be replaced
      with diagnostic workstations. At our institution, a tertiary care center
      specialized in diagnostic imaging, a pair of PC-based review workstations running
      a Digital Imaging and Communications in Medicine (DICOM)-conformant public domain
      software for image display and analysis were installed in two reading rooms.
      Studies are automatically routed after acquisition from the picture archiving and
      communication system (PACS) server to the workstations and remain available for
      visualization for approximately 15 to 20 days. Data from two radiologists and two
      technologists collected over a 3-month period were analyzed, including purpose of
      use, time savings as compared to traditional manual methods, and overall user
      satisfaction. The results from the analysis presented in this work indicate a
      high degree of approval from the users, who report significant timesavings in
      numerous circumstances, in particular when it comes to discussing findings with
      referring physicians whenever films are not available. It also enriches
      communication between radiologists, facilitating peer review on the telephone
      when one of them has questions at the outcome of any given study. One of the main
      advantages associated with the system is the possibility of using it as a
      powerful tool for teaching and research. In conclusion, even when primary
      diagnosis is performed on film, the availability of a PACS for review can be
      helpful to enhance communication with referring physicians, as well as
      technologists and radiologists' efficiency. Our experience shows that it is
      possible to implement such a system using low-cost or freely available components
      without compromising ease of use while keeping costs down, which is a major
      concern in developing countries.

PMID- 11442106
TI  - Investigations on the effect of different characteristics of images sets on the
      performance of a processing scheme for microcalcifications detection in digital
      mammograms.
AB  - The performance of a computer-aided diagnosis (CAD) scheme is closely dependent
      on the database used for its development and tests. The scheme sensitivity can be
      reduced by 15% to 25%, with only 20% of changes in the database cases.
      Previously, we have developed a processing scheme in order to detect clustered
      microcalcifications in digital mammograms, and we have tested such a procedure
      with two different databases. Further evaluations in developing a CAD scheme for
      mammography have indicated the need for more extensive investigation on the
      effects resulting from different characteristics of the images bank used for
      tests. Therefore, this work reports some results regarding such an investigation,
      with a further discussion over characteristics that can affect the performance of
      a CAD scheme.

PMID- 11442107
TI  - Breast magnetic resonance imaging: a computer-based analysis of enhancement
      curves.
AB  - The aim of this work is to report our experience in contrast-enhanced magnetic
      resonance (MR) automatic analysis. This technique is usually used in our practice
      for the diagnosis of breast cancer. Study execution and semiautomatic data
      analysis require at least 1 hour of the radiologist. So, we decided to develop a
      tool that aids the radiologist in locating the regions of neoplastic angiogenesis
      and quickly plotting the enhancement curves. This is not a computer-aided
      diagnostic tool; of course, the curves are interpreting directly by the
      radiologist. We used a programmable graphical and calculus environment (Matlab,
      The Mathworks, Natick, MA) to develop a tool that interfaces directly with our
      picture archiving and communication system (PACS) via Digital Imaging and
      Communications in Medicine (DICOM), receives images, performs images subtraction,
      and shows some possible regions of interest (ROIs), each with an enhancement
      curve. The radiologist can also select other ROIs. The software shows a good
      performance (sensitivity, 100%). A low specificity (25%) is acceptable because
      the software allows the radiologist to save some time during each study.

PMID- 11442108
TI  - A Java viewer to publish Digital Imaging and Communications in Medicine (DICOM)
      radiologic images on the World Wide Web.
AB  - The world wide web is an exciting service that allows one to publish electronic
      documents made of text and images on the internet. Client software called a web
      browser can access these documents, and display and print them. The most popular
      browsers are currently Microsoft Internet Explorer (Microsoft, Redmond, WA) and
      Netscape Communicator (Netscape Communications, Mountain View, CA). These
      browsers can display text in hypertext markup language (HTML) format and images
      in Joint Photographic Expert Group (JPEG) and Graphic Interchange Format (GIF).
      Currently, neither browser can display radiologic images in native Digital
      Imaging and Communications in Medicine (DICOM) format. With the aim to publish
      radiologic images on the internet, we wrote a dedicated Java applet. Our software
      can display radiologic and histologic images in DICOM, JPEG, and GIF formats, and
      provides a a number of functions like windowing and magnification lens. The
      applet is compatible with some web browsers, even the older versions. The
      software is free and available from the author.

PMID- 11442109
TI  - New aspects of using the structural graph-grammar based techniques for
      recognition of selected medical images.
AB  - This report will describe the application of syntactic pattern recognition
      methods for analysis of morphology and recognition of pathologic symptoms of
      chronic diseases such as upper urinary tract disorders. Detection of these
      lesions will be assisted by the special graph-grammar developed in our institute
      for efficient analysis and recognition of such lesions. We present key points of
      methodology and practical results of its application.

PMID- 11442110
TI  - Integrated voice recognition and picture archiving and communication system:
      development and early experience.
AB  - Voice recognition (VR) and picture archiving and communication system (PACS) both
      have advantages and disadvantages in radiologic practice. We describe a fully
      integrated VR/PACS system running on a single platform. Integration optimizes the
      positive features of both systems and creates a synergy that is not otherwise
      realized. The planning and development of the system is described, as well as a
      number of challenges that were addressed. Radiologists have viewed the process
      changes very positively during initial use.

PMID- 11442111
TI  - The evolution of filmless radiology teaching.
AB  - PURPOSE: The transition from hard-copy film to the picture archiving and
      communication systems (PACS) arena is often a long and difficult path, but the
      complete transformation to the digital environment does not end with the
      successful clinical practice utilizing PACS. The next hurdle for academic
      institutions is similar changes in the teaching field. The loss of hardcopy films
      can greatly hinder the radiology teaching file and teaching conference
      experiences. The next step in our growth is the conversion to digital teaching
      files and conferences. The original work 10 years ago with utilizing computers
      linked with laser disks and magneto-optical media, have now evolved into complex
      networks with expanding and relatively cheap storage media, such as CD-ROM and
      easily to navigate graphic-user interfaces such as hypertext markup language
      (HTML) and extensible markup language (XML), for use with multimedia teaching
      tools. CONCLUSIONS: The transition into the digital arena for radiology education
      and interdepartmental conferences can be accomplished through several different
      paths. These include direct transfer of images into a presentation program, as
      well as exportation of images into suitable image file formats for later use.
      There is also the ability to expand the PACS network to include conference rooms.
      Similar training and teaching can allow radiologists to transition into the
      digital environment for future digital teaching file creation as well as
      correlative radiology interdepartmental conferences.

PMID- 11442112
TI  - Adaptable fuzzy C-Means for improved classification as a preprocessing procedure
      of brain parcellation.
AB  - Parcellation, one of several brain analysis methods, is a procedure popular for
      subdividing the regions identified by segmentation into smaller topographically
      defined units. The fuzzy clustering algorithm is mainly used to preprocess
      parcellation into several segmentation methods, because it is very appropriate
      for the characteristics of magnetic resonance imaging (MRI), such as partial
      volume effect and intensity inhomogeneity. However, some gray matter, such as
      basal ganglia and thalamus, may be misclassified into the white matter class
      using the conventional fuzzy C-Means (FCM) algorithm. Parcellation has been
      nearly achieved through manual drawing, but it is a tedious and time-consuming
      process. We propose improved classification using successive fuzzy clustering and
      implementing the parcellation module with the modified graphic user interface
      (GUI) for the convenience of users.

PMID- 11442113
TI  - The skeleton structure--an improved compression algorithm with perfect
      reconstruction.
AB  - This article presents an improved morphological image representation that can be
      used for image compression, obtaining very high compression rates. The new image
      representation described in this work is called skeleton structure and is a
      natural extension of the morphologic structure. This article will present its
      theoretical background, introduce the new representation, and show some
      application examples.

PMID- 11442114
TI  - Calibration of medium-resolution monochrome cathode ray tube displays for the
      purpose of board examinations.
AB  - This report discusses calibration and set-up procedures for medium-resolution
      monochrome cathode ray tubes (CRTs) taken in preparation of the oral portion of
      the board examination of the American Board of Radiology (ABR). The board
      examinations took place in more than 100 rooms of a hotel. There was one display
      station (a computer and the associated CRT display) in each of the hotel rooms
      used for the examinations. The examinations covered the radiologic specialties
      cardiopulmonary, musculoskeletal, gastrointestinal, vascular, pediatric, and
      genitourinary. The software used for set-up and calibration was the VeriLUM 4.0
      package from Image Smiths in Germantown, MD. The set-up included setting minimum
      luminance and maximum luminance, as well as positioning of the CRT in each
      examination room with respect to reflections of roomlights. The calibration for
      the grey scale rendition was done meeting the Digital Imaging and communication
      in Medicine (DICOM) 14 Standard Display Function. We describe these procedures,
      and present the calibration data in. tables and graphs, listing initial values of
      minimum luminance, maximum luminance, and grey scale rendition (DICOM 14 standard
      display function). Changes of these parameters over the duration of the
      examination were observed and recorded on 11 monitors in a particular room. These
      changes strongly suggest that all calibrated CRTs be monitored over the duration
      of the examination. In addition, other CRT performance data affecting image
      quality such as spatial resolution should be included in set-up and image quality
      control procedures.

PMID- 11442115
TI  - Digital radiology equipment acquisition and installation procedures: a team
      approach at Mayo Clinic, Rochester, MN.
AB  - Digital imaging system integration is a complex process. A project team and a
      defined process for system planning, evaluation, and implementation can improve
      the chance for success. In this presentation, our project team relates their
      experiences.

PMID- 11442116
TI  - An overview of a picture archiving and communications system procurement.
AB  - The implementation and integration of a picture archiving and communications
      system (PACS) wil be one of the most significant initiatives a healthcare
      enterprise will undertake. Developing processes that establish the needs of the
      users, support strategic initiatives, and address risk management is not trivial.
      The development of a plan that provides the PACS selection committees with a step
      by-step roadmap to seek and procure the PACS best suited to their workflow is a
      valuable tool. This report is a high-level overview of steps to consider when
      establishing the process to procure PACS.

PMID- 11442117
TI  - How many people does it take to operate a picture archiving and communication
      system?
AB  - The most frequently asked question without a correct answer is: "Just how many
      people does it take to operate a picture archiving and communication system
      (PACS)?" At Texas Children's Hospital, our consensus is that we do not yet know.
      As soon as we felt we had adequate staffing to provide timely response for
      routine services, we found that including the Intensive Care Units (ICUs)
      increased our demand for urgent response beyond our capacity. The addition of
      inpatient bedside imaging to PACS also increased the demand for round-the-clock
      and weekend PACS services. Our answer to the staffing question changes every
      year, in accordance with changes in the scope of services that our PACS is
      expected to provide. Our administration drew up a 5-year plan for PACS
      implementation, concentrating on purchase and installation of equipment, but
      neglected to estimate requirements for full-time equivalents (FTEs) for PACS. Our
      administration reasonably assumed that existing employees would be galvanized
      into PACS personnel. It is now clear that new FTEs need to be created strictly
      for the PACS service. Our 5-year plan also did not anticipate significant changes
      in the extent of our healthcare enterprise. Our PACS accommodates limited remote
      service: providing a PACS Analyst to travel to the site when a problem is not
      resolved remotely is another demand on staffing. Our PACS service was formed
      using staffing numbers based on assumptions about the minimum number of employees
      needed to perform routine duties, field trouble calls, conduct training, and work
      on special projects, such as adding new acquisition modalities or troubleshooting
      longstanding problems. This staffing was based on a single shift operation, with
      on-call coverage for second, third, and weekend shifts. The number of employees
      also considered absences for vacation, sick leave, and training. The service has
      administrative overhead that should be covered by a secretary. Someone is also
      needed to supervise the team. Once the number of personnel is determined,
      detailed definition of qualifications and responsibilities is required. Each job
      description must accurately reflect what is expected of the employee, but must be
      constructed in such a way to be graded appropriately by Human Resources, without
      excluding potentially desirable applicants. In addition to competitive pay, other
      factors play an important role in recruiting and retention. These include
      training that the hospital provides, opportunities for advancement, relief from
      menial duties, adequate working space and facilities, and opportunities for self
      development. There is high turnover of personnel in computer services, and we are
      in a highly competitive market. The correct number of FTEs must consider that we
      will have to operate the PACS during periods when one or more positions are open
      or occupied by "greenhorns." In our case, where the vendor provides on-site
      service engineers, we are able to operate with fewer FTEs. The more distant and
      tenuous our vendor support, the more we would need to depend on hospital FTEs.
      While remote vendor maintenance is helpful, it is not useful in reducing the
      number of FTEs. Instead of adding PACS responsibilities to supervisors of imaging
      services, we are creating new PACS FTEs outside the PACS service. The idea is to
      give imaging supervisors the assets they need to perform the additional tasks
      involving PACS, such as first-line response to trouble, user training, and
      quality-control oversight. It also frees up PACS service personnel to deal with
      training and problems with customers outside the Radiology Department.

PMID- 11442118
TI  - Developing policies and procedures for a picture archiving and communication
      system.
AB  - Policies and procedures (P&P) constitute the mechanism for planning,
      standardizing, and documenting the provision of clinical services. Upon approval
      by hospital management, the P&P is an official statement of hospital rules and
      regulations. Each P&P establishes organizational responsibility for providing
      services. P&P are a mechanism for communicating standard operating procedures to
      hospital and medical staff. P&P serve as a reference document for unusual events,
      as well as routine procedures. P&P are often reviewed by inspection teams from
      the Joint Commission on Accreditation of Hospital Organizations (JCAHO) to
      determine whether the hospital has documented systematic practices. A picture
      archival and communications system (PACS) provides a new vehicle for providing
      radiology services. P&P that were designed for conventional film-based imaging
      are often not appropriate for electronic imaging. Because PACS is new and not yet
      widespread, good examples of PACS P&P are not yet available. JCAHO has no
      official requirements for PACS: PACS is viewed only as a means for the hospital
      to accomplish its work. Successful P&P development is a team effort, drafted by
      personnel responsible for executing the procedure, assisted by staff proficient
      in PACS technology, and tested in the field. The P&P should be reviewed and
      approved by management personnel knowledgeable about hospital and imaging
      operations. P&P should be written in clear and concise language. Successful P&P
      development is an ongoing effort. P&P must be periodically reviewed and updated
      to reflect changes in PACS technology and changes in clinical operations. New P&P
      must be developed when a deficit is noted. PACS security is a good example of a
      topic worthy of P&P development, especially in the face of the Health Insurance
      Portability and Accountability Act (HIPAA) legislation of 1996. What are the
      provisions for access control? Does the system include a feature for automatic
      shut-off of the software? Are there "generic" passwords and log-ins shared by a
      community of users? How are passwords assigned and how frequently are they
      changed? What security measures are in place to assure passwords are given to the
      appropriate user? Who grants and denies access? Service calls are another topic
      for P&P. Who initiates a service call? What is the process for escalating a
      service call from the operator level to the vendor? What immediate actions are
      expected by the operator in order to restore PACS services? How are service
      events documented? Who is responsible for determining when "downtime" procedures
      should be initiated or suspended? When our hospital's total electrical system had
      to be shut down for an extended period, we found that a P&P was lacking for a
      task as mundane as shutting down and restarting our PACS components. What is the
      sequence for the shutdown? Who is responsible for shutting down and restarting?
      How long can the devices operate on uninteruptible power supplies (UPS)? What
      components are on emergency power? Should we expect the components to survive the
      switchover to generator power? Developing this P&P was worth the effort: it made
      the PACS more fault-tolerant and served as a reference document 3 years later
      when expansion of our physical plant required two more power outages.

PMID- 11442119
TI  - A comparison of image characteristics and convenience in panoramic radiography
      using charge-coupled device, storage phosphor, and film receptors.
AB  - This study compared the image layer characteristics, dose requirements, and
      convenience in use of panoramic radiography using each of four different image
      receptors including traditional indirect exposure x-ray film, a storage phosphor
      system, and two solid-state sensors. The OP 100 D (Instrumentarium Imaging,
      Tuusula, Finland) charge-coupled device (CCD) sensor provided an instant image
      with a wide focal trough, making patient positioning error unlikely, but at the
      same time required a patient dose higher than that used with film. While the
      DigiPan (Trex/Trophy, Marne-la-Vallee, France) CCD significantly reduced the
      patient dose to radiation and also provided an instant image, the focal trough
      was narrower making patient positioning error more likely. The storage phosphor
      system provided high resolution and a reasonable focal trough width, but the
      procedure took longer than traditional film radiography and did not provide a
      dose saving.

PMID- 11442120
TI  - Elastic registration of x-ray mammograms and three-dimensional magnetic resonance
      imaging data.
AB  - Major problems in treating breast cancer are the early detection of tumors and
      accurate biopsy of small volumes of breast (mamma) tissue. This report presents
      an elastic registration algorithm of two x-ray mammograms and a corresponding
      magnetic resonance imaging (MRI) volume. To cope with the soft tissue deformation
      of the breast during mammography, a two-dimensional model of breast deformation
      behavior is used as an elastic transformation. Normalized mutual information is
      employed as a measure of similarity. Regions of interest in the uncompressed x
      ray mammograms are projected into the MRI volume to determine their three
      dimensional origin.

PMID- 11442121
TI  - A Bayesian network for diagnosis of primary bone tumors.
AB  - The authors developed a Bayesian network to differentiate among five benign and
      five malignant neoplasms of the appendicular skeleton using the patient's age and
      sex and 17 radiographic characteristics. In preliminary evaluation with
      physicians in training, the model identified the correct diagnosis in 19 cases
      (68%), and included the correct diagnosis among the two most probable diagnoses
      in 25 cases (89%). Bayesian networks can capture and apply knowledge of primary
      bone neoplasms. Further testing and refinement of the model are underway.

PMID- 11442122
TI  - A use of a neural network to evaluate contrast enhancement curves in breast
      magnetic resonance images.
AB  - For the diagnosis of breast cancer using magnetic resonance imaging (MRI), one of
      the most important parameters is the analysis of contrast enhancement. A three
      dimensional MR sequence is applied before and five times after bolus injection of
      paramagnetic contrast medium (Gd-DTPA). The dynamics of absorption are described
      by a time/intensity enhancement curve, which reports the mean intensity of the MR
      signal in a small region of interest (ROI) for about 8 minutes after contrast
      injection. The aim of our study was to use an artificial neural network to
      automatically classify the enhancement curves as "benign" or "malignant." We used
      a classic feed-forward back-propagation neural network, with three layers: five
      input nodes, two hidden nodes, and one output node. The network has been trained
      with 26 pathologic curves (10 invasive carcinoma [K], two carcinoma-in-situ
      [DCIS], and 14 benign lesion [B]). The trained network has been tested with 58
      curves (36 K, one DCIS, 21 B). The network was able to correctly identify the
      test curves with a sensitivity of 76% and a specificity of 90%. For comparison,
      the same set of curves was analyzed separately by two radiologists (a breast MR
      expert and a resident radiologist). The first correctly interpreted the curves
      with a sensitivity of 76% and a specificity of 90%, while the second scored 59%
      for sensitivity and 90% for specificity. These results demonstrate that a trained
      neural network recognizes the pathologic curves at least as well as an expert
      radiologist. This algorithm can help the radiologist attain rapid and affordable
      screening of a large number of ROIs. A complete automatic computer-aided
      diagnosis support system should find a number of potentially interesting ROIs and
      automatically analyze the enhancement curves for each ROI by neural networks,
      reporting to the radiologist only the potentially pathologic ROIs for a more
      accurate, manual, repeated evaluation.

PMID- 11442123
TI  - Evaluating a voice recognition system: finding the right product for your
      department.
AB  - The Department of Radiology at the University of Utah Health Sciences Center has
      been in the process of transitioning from the traditional film-based department
      to a digital imaging department for the past 2 years. The department is now
      transitioning from the traditional method of dictating reports (dictation by
      radiologist to transcription to review and signing by radiologist) to a voice
      recognition system. The transition to digital operations will not be complete
      until we have the ability to directly interface the dictation process with the
      image review process. Voice recognition technology has advanced to the level
      where it can and should be an integral part of the new way of working in
      radiology and is an integral part of an efficient digital imaging department. The
      transition to voice recognition requires the task of identifying the product and
      the company that will best meet a department's needs. This report introduces the
      methods we used to evaluate the vendors and the products available as we made our
      purchasing decision. We discuss our evaluation method and provide a checklist
      that can be used by other departments to assist with their evaluation process.
      The criteria used in the evaluation process fall into the following major
      categories: user operations, technical infrastructure, medical dictionary, system
      interfaces, service support, cost, and company strength. Conclusions drawn from
      our evaluation process will be detailed, with the intention being to shorten the
      process for others as they embark on a similar venture. As more and more
      organizations investigate the many products and services that are now being
      offered to enhance the operations of a radiology department, it becomes
      increasingly important that solid methods are used to most effectively evaluate
      the new products. This report should help others complete the task of evaluating
      a voice recognition system and may be adaptable to other products as well.

PMID- 11442124
TI  - Study status consistency and duplicate-read protection in a distributed
      architecture.
AB  - This presentation will discuss the benefits and pitfalls of implementing a study
      status and duplicate-read protection mechanism within a distributed picture
      archiving and communication system (PACS) architecture. There are many advantages
      to a distributed PACS network in which image studies are proactively pushed to
      reading stations before they are required by a radiologist. The absence of a
      central server, which serves on demand, makes managing study status and
      protecting against duplicate reads challenging. The system to manage study status
      and read access must be efficient, robust, and easy to administer. A system is
      presented that accomplishes these goals while maintaining the advantages of a
      distributed architecture. METHODS: The basic workflow of the system is that image
      studies acquired at a modality device are automatically sent to an archive
      server. Using a set of advanced routing rules, the archive automatically routes
      studies to diagnostic workstations where studies are candidates for diagnostic
      read. The workstations display a list of all local studies available for reading.
      A monitor application running on the workstations coordinates access to studies
      for diagnostic read. Once the status of a study has been changed, the
      workstations on the networks and the archive are notified, which causes the study
      to be automatically removed from any list on a workstation where it might be a
      read candidate. RESULTS: Implementation of this system provides a balanced
      workflow throughout the system while minimizing the need for costly high-speed
      network hardware. Additionally studies are read as soon as they are available by
      the next available radiologist. This workflow is enabled without the need for
      specific interaction by any of the radiologists on the network. By having the
      images available at the workstation in an organized worklist, this methodology
      increases the efficiency of the radiologist. CONCLUSION: The implementation of
      this system enables a radiology department, or even a specialty group within a
      department, to gain the benefit of a distributed system as well as the benefits
      provided by a central-server architecture. This can be done very cost effectively
      with minimal configuration overhead and hardware requirements.

PMID- 11442125
TI  - Enterprise-class Digital Imaging and Communications in Medicine (DICOM) image
      infrastructure.
AB  - Most current picture archiving and communication systems (PACS) are designed for
      a single department or a single modality. Few PACS installations have been
      deployed that support the needs of the hospital or the entire Integrated Delivery
      Network (IDN). The authors propose a new image management architecture that can
      support a large, distributed enterprise.

PMID- 11442126
TI  - Puncture-proof picture archiving and communication system.
AB  - As we become increasingly dependent on our picture archiving and communications
      system (PACS) for the clinical practice of medicine, the demand for improved
      reliability becomes urgent. Borrowing principles from the discipline of
      Reliability Engineering, we have identified components of our system that
      constitute single points of failure and have endeavored to eliminate these
      through redundant components and manual work-around procedures. To assess the
      adequacy of our preparations, we have identified a set of plausible events that
      could interfere with the function of one or more of our PACS components. These
      events could be as simple as the loss of the network connection to a single
      component or as broad as the loss of our central data center. We have identified
      the need to continue to operate during adverse conditions, as well as the
      requirement to recover rapidly from major disruptions in service. This assessment
      led us to modify the physical locations of central PACS components within our
      physical plant. We are also taking advantage of actual disruptive events
      coincident with a major expansion of our facility to test our recovery
      procedures. Based on our recognition of the vital nature of our electronic images
      for patient care, we are now recording electronic images in two copies on
      disparate media. The image database is critical to both continued operations and
      recovery. Restoration of the database from periodic tape backups with a 24-hour
      cycle time may not support our clinical scenario: acquisition modalities have a
      limited local storage capacity, some of which will not contain the daily
      workload. Restoration of the database from the archived media is an exceedingly
      slow process, that will likely not meet our requirement to restore clinical
      operations without significant delay. Our PACS vendor is working on concurrent
      image databases that would be capable of nearly immediate switchover and
      recovery.

PMID- 11442127
TI  - Finding the optimal picture archiving and communication system (PACS)
      architecture: a comparison of three PACS designs.
AB  - PURPOSE: At present, there are two basic picture archiving and communication
      system (PACS) architectures: centralized with a central cache and controller, and
      distributed with a distributed cache and central controller. A third architecture
      proposed here is an autonomous one with a distributed cache and no controller.
      This report will investigate the performance (as measured be central processing
      unit [CPU] and network load, scalability, and examination retrieval and display
      latency) of these three types. METHODS: The distributed PACS architecture will be
      simulated using an IMPAX R3.5 (AGFA, Ridgefield Park, NJ) PACS, while the
      centralized design will be simulated using an IMPAX R4 (AGFA) PACS. The
      autonomous system will be designed and implemented in-house. The autonomous
      system consists of two types of entities: basic components such as acquisition
      gateways, display stations, and long-term archives, and registry servers, which
      store global state information about the individual PACS components. The key
      feature of the autonomous system will be the replacement of the central PACS
      controller by the registry servers. In this scenario the registry servers monitor
      the interactions between the components, but do not directly govern them. Instead
      each component will contain the application logic it requires and will use the
      state information from the registry servers to take the appropriate action, such
      as routing images, prefetching studies, and expiring images from near line cache.
      In addition the routing of examinations will be optimized to reduce the
      duplication of image data. Display stations will be categorized by specialty
      (neuroradiology, pediatrics, chest, etc) and will retrieve studies for display on
      demand from intermediate servers dedicated to the corresponding specialty.
      Studies will be routed only to the intermediate servers and not to display
      stations. RESULTS: By distributing the application logic, an autonomous PACS
      architecture can provide increased fault tolerance and therefore increased
      uptime. In addition, the lack of a central controller and the use of intermediate
      servers improve the scalability of the system, as well as reduce CPU and network
      loads.

PMID- 11442128
TI  - The Radiological Society of North America's Medical Image Resource Center: an
      update.
AB  - The Radiological Society of North America (RSNA) has initiated a long-term
      project called the Medical Image Resource Center (MIRC). The overall goal of the
      effort is to create an on-line library of medical images and related information
      and to maintain and index a number of other medical image resources. The
      rationale for the project, a summary of the overall requirements and objectives,
      and a finally a brief description of the future plans for MIRC are presented.

PMID- 11442129
TI  - Designing fault-tolerant distributed archives for picture archiving and
      communication systems.
AB  - PURPOSE: Distributed archives in a picture archiving and communication system
      (PACS) environment can provide added fault tolerance and fail-over capability, as
      well as increased load capacity at a more economical price than traditional 'high
      availability" systems. Systems can be configured with varying levels of fault
      tolerance, depending on the amount of redundancy desired. There is, however, a
      direct correlation between the level of hardware redundancy and cost to
      implement. This presentation details the system design for fault-tolerant
      distributed archives as well as several options for redundancy, referencing
      implementation of a fault-tolerant archive system at the University of Utah.
      METHODS: The distributed archive system described here is based on Image Devices'
      image archive software, which can be implemented on multiple individual archive
      servers in order to distribute archive functionality and operational load. The
      configuration and implementation of the individual servers together make up the
      distributed archive system and does not impact the ability of the system to be
      scaled to meet future requirements. Several implementation and configuration
      options exist, including the ability for servers to maintain replicated databases
      containing patient and image information. Thus, each archive can be aware of all
      information and the location of this information within the distributed archive
      system. RESULTS: The goal is to produce systems that will still be operational in
      the event of any single point of failure, ie, a network connection failure
      between facilities or the failure of a single archive server within the
      distributed system. During normal operation, workload for image acquisition,
      image routing and image query requests will be distributed between the archive
      servers. If the system is deployed in a multifacility environment, each archive
      server can be configured to be responsible for the acquisition and image
      distribution management within that server's local facility. If the system is
      deployed in a single facility environment, load can be distributed evenly between
      the archive servers based on an understanding of the workload requirements
      generated be each acquisition and display device in the system. In the event that
      an archive server fails, other archive servers within the system will have the
      ability to provide some or all of the failed server's functionality. The degree
      of fail-over capability is dependent on the archive server's configuration as
      well as hardware redundancy employed. Three levels of fault-tolerant design can
      be achieved with this system architecture: (1) duplicate work capability only;
      (2) duplicate work capability and short-term image cache; (3) duplicate work
      capability, short-term image cache, and longterm image archival. Using the basic
      fault-tolerant design above, we have implemented a multifacility distributed
      archive system at the University of Utah. This system was implemented at a
      fraction of the cost of true "high-availability" archive architectures yet
      provides constant up time for the PACS system. If the network connection between
      the two locations goes down, each site is still fully functional for soft-copy
      read, as well as image acquisition and distribution. If either of the archive
      servers goes down, the image sources are redirected to the other archive server.
      The operational server then handles image distribution for both locations. Access
      to images in the short-term image cache is available to both archive servers and
      is not affected by loss of the network connection or remote server. Because there
      is ony one long-term archive device, the ability to retrieve images from long
      term storage is the only function compromised by a network or server failure.
      CONCLUSION: By implementing distributed archives in a PACS environment, it is
      possible to achieve a highly fault-tolerant system without the expense of high
      availability hardware and software. The design concepts outlined here can be
      applied to any PACS system that supports distributed archive functionality.

PMID- 11442130
TI  - Management of the picture archiving and communications system archive at Texas
      Children's Hospital.
AB  - As hospitals convert from conventional film-based imaging to picture archival and
      communications systems (PACS), methods for managing an enormous library of images
      must change considerably. While most hospitals are required to retain general,
      nonmammographic, radiologic images for 7 years beyond the examination date, our
      pediatric hospital must maintain images until the child's eighteenth birthday,
      plus the 5-year statute of limitations. Although the physical extent of an
      electronic archive is tiny compared with a film archive, a long-range strategy is
      required to ensure that electronic images acquired today can be retrieved and
      viewed 23 years in the future. Challenges to the long-term stability of the
      electronic archive include the limited and uncertain shelf life of high-density
      electronic storage media, the finite maintainability of the electromechanical
      systems for reading the media, the short product lifetime of software for
      accessing the images, rapid development of higher density storage products, and
      the exponential advancement of computer and networking technology that fuels
      product obsolescence. Since we cannot assure the function of our current archive
      in two decades, we are committed to a continual process of migration of old
      electronic image data to newer media and systems. As an early-adopter of PACS
      technology, Texas Children's Hospital's (TCH) archive management experience is
      relevant to others. Although not filled to capacity, our first digital archive,
      based on phase-change write-once-read-many (WORM) technology, was forced into an
      inactive status by software and hardware changes. Our second set of archives was
      partially filled with low-density magneto-optical disk (MOD) media, when the
      drives were upgraded to high density and then filled to capacity. This
      undesirable situation forced us into shelf management of media. Our third
      generation archive is based on a helical tape library with the capacity to
      contain 7 years of examinations. We will describe the motivation for data
      migration, limitations in the methods available to perform the migration, and
      unanticipated benefits of the migration process.

PMID- 11442131
TI  - What Digital Imaging and Communication in Medicine (DICOM) could look like in
      common object request broker (CORBA) and extensible markup language (XML).
AB  - Common object request broker architecture (CORBA) is a method for invoking
      distributed objects across a network. There has been some activity in applying
      this software technology to Digital Imaging and Communications in Medicine
      (DICOM), but no documented demonstration of how this would actually work. We
      report a CORBA demonstration that is functionally equivalent and in some ways
      superior to the DICOM communication protocol. In addition, in and outside of
      medicine, there is great interest in the use of extensible markup language (XML)
      to provide interoperation between databases. An example implementation of the
      DICOM data structure in XML will also be demonstrated. Using Visibroker ORB from
      Inprise (Scotts Valley, CA), a test bed was developed to simulate the principle
      DICOM operations: store, query, and retrieve (SQR). SQR is the most common
      interaction between a modality device application entity (AE) such as a computed
      tomography (CT) scanner, and a storage component, as well as between a storage
      component and a workstation. The storage of a CT study by invoking one of several
      storage objects residing on a network was simulated and demonstrated. In
      addition, XML database descriptors were used to facilitate the transfer of DICOM
      header information between independent databases. CORBA is demonstrated to have
      great potential for the next version of DICOM. It can provide redundant
      protection against single points of failure. XML appears to be an excellent
      method of providing interaction between separate databases managing the DICOM
      information object model, and may therefore eliminate the common use of
      proprietary client-server databases in commercial implementations of picture
      archiving and communication systems (PACS).

PMID- 11442132
TI  - Planning for a multi-imaging center picture archiving and communications system.
AB  - There are fundamental differences in planning and configuring a picture archiving
      and communications system (PACS) for a multisite imaging practice as compared to
      a hospital-based radiology department. In the for-profit, multi-imaging center
      environment, return on investment is more critical and the distributed nature of
      radiology operations presents complex communications, infrastructure, archiving,
      workflow, and distribution requirements. This article discusses desired outcomes
      for a multi-imaging center PACS and the planning, functional, technical, and
      support requirements necessary to achieve those outcomes.

PMID- 11442133
TI  - Integrating digital educational content created and stored within disparate
      software environments: an extensible markup language (XML) solution in real-world
      use.
AB  - OBJECTIVE: To provide a standardized and scaleable mechanism for exchanging
      digital radiologic educational content between software systems that use
      disparate authoring, storage, and presentation technologies. MATERIALS/METHODS:
      Our institution uses two distinct software systems for creating educational
      content for radiology. Each system is used to create in-house educational content
      as well as commercial educational products. One system is an authoring and
      viewing application that facilitates the input and storage of hierarchical
      knowledge and associated imagery, and is capable of supporting a variety of
      entity relationships. This system is primarily used for the production and
      subsequent viewing of educational CD-ROMS. Another software system is primarily
      used for radiologic education on the world wide web. This system facilitates
      input and storage of interactive knowledge and associated imagery, delivering
      this content over the internet in a Socratic manner simulating in-person
      interaction with an expert. A subset of knowledge entities common to both systems
      was derived. An additional subset of knowledge entities that could be
      bidirectionally mapped via algorithmic transforms was also derived. An extensible
      markup language (XML) object model and associated lexicon were then created to
      represent these knowledge entities and their interactive behaviors. Forward
      looking attention was exercised in the creation of the object model in order to
      facilitate straightforward future integration of other sources of educational
      content. XML generators and interpreters were written for both systems. RESULTS:
      Deriving the XML object model and lexicon was the most critical and time
      consuming aspect of the project. The coding of the XML generators and
      interpreters required only a few hours for each environment. Subsequently, the
      transfer of hundreds of educational cases and thematic presentations between the
      systems can now be accomplished in a matter of minutes. The use of algorithmic
      transforms results in nearly 100% transfer of context as well as content, thus
      providing "presentation-ready" outcomes. CONCLUSION: The automation of knowledge
      exchange between dissimilar digital teaching environments magnifies the efforts
      of educators and enriches the learning experience for participants. XML is a
      powerful and useful mechanism for transfering educational content, as well as the
      context and interactive behaviors of such content, between disparate systems.

PMID- 11442134
TI  - Integrating digital teaching-file systems with off-the-shelf presentation
      software to facilitate speaker-led conferences.
AB  - OBJECTIVE: Develop methods for automated transfer of images and associated text
      from a teaching-file repository into presentation material for speaker-led
      conferences. MATERIALS/METHODS: Our institution uses a Microsoft Windows
      (Microsoft Corp, Redmond, WA) software application to maintain a digital teaching
      file database that can store and retrieve content in a case-centric fashion.
      Virtually any number of images can be stored with any given case. Cases and their
      associated images can be retrieved via a module that supports searches by
      American College of Radiology (ACR) code and by free-text Boolean queries on the
      history, findings, diagnosis, and discussion components of a case. In addition to
      the software system serving directly as an interactive teaching tool, the digital
      teaching file itself serves as an image repository and resource for attending
      radiologists who create their own presentations and lectures. To better support
      this use, software modules were developed for interprocess communication and
      automated creation of Powerpoint slides. These modules are fully integrated with
      the teaching-file software application. A single image or a set of selected
      images can be automatically made into individual slides with two mouse clicks.
      Images are automatically centered and optimally sized. A slide title is
      automatically rendered from the user's preference of the case history or
      diagnosis (stored with the case), or via the entry of freeform text. We describe
      the programming techniques that are used, as well as how several features of the
      operating system and Powerpoint itself can be integrated with a customized
      software application to facilitate this objective. RESULTS: The creation of
      presentation-ready Powerpoint slides is fully automated from within our teaching
      file application, and the time required to create a presentation compared to the
      conventional method of manually seeking and inserting files from within
      Powerpoint itself, on a per-slide basis, is drastically reduced. The benefits are
      magnified by having all imagery stored within an organized and searchable
      database system so that desired images can be easily located. CONCLUSION: A
      digital teaching-file system can serve as a useful image repository for purposes
      ancillary to direct computerized instruction. Software that supports these uses,
      such as the automated creation of presentation material for speaker-led
      conferences, facilitates the radiologist's role as an educator.

PMID- 11442135
TI  - The emotional Stroop effect in anxiety disorders: general emotional or disorder
      specificity?
AB  - Selective attentional biases, often documented with a modified Stroop task, are
      considered to play an important role in the etiology and maintenance of anxiety.
      Two competing explanations for these effects are selectivity for highly emotional
      words in general vs. selectivity for disorder-specific words. We tested these
      explanations in 32 patients with generalized anxiety disorder (GAD), 29 patients
      with social phobia (SP), and 31 non-anxious controls. Stimuli were of four kinds:
      GAD-related words, SP-related words, words with a neutral valence, and words with
      a positive valence. Different attentional biases were observed: GAD patients were
      slowed by all types of emotional words, while SP patients were distracted
      specifically by speech-related words.

PMID- 11442136
TI  - Is there a negative association between anxiety sensitivity and arousal
      increasing substances and activities?
AB  - Little research has addressed McNally's hypothesis [(1996). Anxiety sensitivity
      is distinguishable from trait anxiety. In: R. M. Rapee (Ed.), Current
      controversies in the anxiety disorders (pp. 214-227). New York: The Guilford
      Press.] that anxiety sensitivity (AS) should be negatively associated with the
      use of arousal-increasing substances. In the present study, we examined the
      relationship between AS and the self-reported use of two widely available
      stimulants--nicotine and caffeine--and exercise frequency in a sample of 256
      university students. A measure of trait anxiety was also incorporated within the
      design. The associations between use of both substances and levels of AS and
      trait anxiety were weak and nonsignificant. Although inconsistent with McNally's
      hypothesis, some significant findings were found when the lower-order components
      of AS (i.e., fears of physical, psychological, and publicly observable symptoms
      of anxiety) were examined. The associations between exercise frequency and the
      anxiety measures, indicating a negative relationship, were generally consistent
      with McNally's hypothesis. Implications of these findings are discussed with
      reference to future investigation.

PMID- 11442137
TI  - The effects of impression management demands on heart rate, self-reported social
      anxiety, and social competence in undergraduate males.
AB  - The effects of self-presentation demands were evaluated through conversational
      probe (CP) role-play tasks. Participants (N = 29) were required to manage their
      self-presentations (i.e., the impression they made, in each of two conditions).
      During high impression management (IM) demand, participants were evaluated on
      their performance. During Low IM demand, participants evaluated a confederate's
      performance. The High IM demand condition produced significantly higher heart
      rate (HR) and self-reported anxiety. HR and self-reported anxiety accounted for a
      significant amount of the variance in criterion measures of social competence.
      Greater social competence during High IM was associated with higher HR. Greater
      social competence during Low IM was associated with lower HR and lower self
      reported anxiety. Although preliminary, these results suggest that uncontrolled
      IM demands contributed to mixed results found within and between social anxiety
      studies in the literature. Implications for the treatment of social anxiety are
      discussed.

PMID- 11442138
TI  - Assessment of self-statements in agoraphobic situations construction and
      psychometric evaluation of the Agoraphobic Self-Statements Questionnaire (ASQ).
AB  - The study describes the development and psychometric evaluation of a self-report
      questionnaire for use in both treatment-outcome research and process studies: the
      Agoraphobic Self-Statements Questionnaire (ASQ). The ASQ comprises two subscales:
      a positive self-statements subscale and a negative self-statements subscale.
      Confirmatory factor analysis showed that, with the exception of one item, the
      proposed bidimensional structure of the ASQ reappeared in a second agoraphobic
      patient sample. Internal consistency of both subscales was satisfactory. Both
      subscales appeared to be sensitive to change in treatment and discriminated
      between agoraphobic patients and normal controls. Construct validity of the
      negative subscale was satisfactory, whilst additional validation of the positive
      subscale is required. Findings also revealed that positive thinking may serve as
      a coping device and that the occurrence of negative self-statements might be
      considered a sine qua non for the occurrence of positive self-statements. It is
      concluded that the ASQ can contribute to the understanding of cognitive processes
      during treatment of agoraphobia.

PMID- 11442139
TI  - Social anxiety in college students.
AB  - Individuals with social phobia often hold erroneous beliefs about the extent to
      which others experience symptoms of social anxiety and the ways in which others
      evaluate people who appear to be anxious. The purpose of this study was to: (a)
      provide normative data on the frequency with which individuals in a nonclinical
      sample experience particular symptoms of social anxiety (e.g., sweating, shaking,
      etc.); (b) to examine how the perception of anxiety in others influences
      participants' immediate impressions of various personal characteristics (e.g.,
      intelligence, attractiveness, etc); and, (c) investigate the relationship between
      social anxiety and perceptions regarding others who appear to be anxious. Eighty
      one undergraduate students completed self-report measures of social anxiety and
      social desirability, and then rated the degree to which their impressions of
      various personal characteristics were influenced when another individual was
      perceived to be anxious. Results suggested that the vast majority of individuals
      experience symptoms of anxiety in social situations from time to time. In
      addition, individuals who themselves reported elevated social anxiety were more
      likely than individuals less socially anxious to judge others who appear anxious
      to have less strength of character and to be less attractive and more
      compassionate compared to others who do not appear anxious. Clinical implications
      of these results are discussed.

PMID- 11442140
TI  - The utility of the ASI factors in predicting response to voluntary
      hyperventilation among nonclinical participants.
AB  - Empirical research has demonstrated that the Anxiety Sensitivity Index (ASI)
      contains three separable factors and that ASI total scores are useful in
      predicting response to physiological challenge procedures. Little is known,
      however, of the predictive capability of the ASI factors. This study investigated
      the utility of the three factors of the ASI compared to ASI total scores and the
      STAI-T, a more general measure of trait anxiety, in predicting response to
      hyperventilation. As expected, the ASI total score was a significant predictor of
      response to hyperventilation, while the STAI-T was not. Using multiple
      regression, when the physical concerns factor was entered first, the social
      concerns and mental incapacitation factors of the ASI were not significant
      predictors of response to hyperventilation. Furthermore, when the physical
      concerns factor was entered into a regression equation followed by the remainder
      of the ASI items, only the physical concerns factor remained a significant
      predictor of response to hyperventilation. These results suggest that while
      response to physiological challenge procedures is predicted by ASI total scores,
      it may be best predicted by the physical concerns factor, and that the mental
      incapacitation and social concerns subscales do not play key roles in predicting
      response to physiological challenge procedures.

PMID- 11442141
TI  - State and trait anxiety revisited.
AB  - State and trait anxiety theory and assessment are reviewed. The person (trait
      anxiety) and the situation are important in determining levels of state anxiety.
      The facet of trait anxiety and the stressful situation must be congruent in order
      to evoke increases in state anxiety. The multidimensional interaction model is
      reviewed and empirical research is presented. A discussion of anxiety viewed in a
      dimensional versus a categorical conceptualization is presented. Misconceptions
      regarding the multidimensionality of trait anxiety are discussed. Finally, it is
      concluded that anxiety should be viewed as a dimensional construct and that the
      multidimensionality of state and trait anxiety should be considered in both
      theory and assessment.

PMID- 11442142
TI  - Relationships between the anxiety sensitivity index, the suffocation fear scale,
      and responses to CO2 inhalation.
AB  - Interest in documenting ways to predict anxious responding in panic disorder (PD)
      patients has proliferated recently in the literature. In the current study, two
      self-report measures were assessed to determine their relative utility in
      predicting responses to a panicogenic challenge. The Anxiety Sensitivity Index
      (ASI) and the Suffocation Fear Scale (SFS) were evaluated by correlating scores
      on these measures with reactions to inhalation of 35% carbon dioxide (CO2),
      assessed via anxiety ratings, panic symptom intensity, tidal volume (VT) and
      respiratory rate (RR). A sample of 14 PD patients and 14 matched control (MC)
      participants demonstrated that the relationship between ASI scores and responses
      to 35% CO2 were stronger than the relationship between SFS scores and responses
      to CO2. Specifically, both respiratory responses (VT and RR) and self-reported
      reactions (anxiety and symptom intensity) were significantly correlated with
      scores on the ASI. In contrast, scores on the SFS were significantly correlated
      with only one measure of respiratory change (VT). Although preliminary, these
      data indicate that the ASI may be a more useful tool than the SFS in predicting
      self-reported and respiratory responses to CO2 challenges.

PMID- 11442143
TI  - On the association between valproate and polycystic ovary syndrome.
AB  - Recent studies by Isojarvi et al. have raised the issue of an increased incidence
      of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate
      (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries
      (PCO) are a common finding, with a prevalence >20% in the general population, and
      are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is
      comparatively rare: few women with PCO have fully developed PCOS, which includes
      hirsutism, acne, obesity, hypofertility. hyperandrogenemia, and menstrual
      disorders. From an extensive review of the current literature, it appears that
      there are no reliable data on the actual prevalence of PCOS in normal women and
      in women with epilepsy. The pathogenesis of PCO is multifactorial, including
      genetic predisposition and the intervention of environmental factors, among which
      weight gain and hyperinsulinism with insulin resistance may play a part. The
      roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors
      are still debated. PCO and PCOS appear to be more frequent in women with
      epilepsy, but there are no reliable data showing a greater prevalence after VPA.
      The recent studies by Isojarvi et al. may have been biased by the retrospective
      selection of patients. To date, there is no reason to contraindicate the use of
      VPA in women with epilepsy. However, patients should be informed about the risk
      of weight gain and its consequences.

PMID- 11442144
TI  - On the association between valproate and polycystic ovary syndrome: a response
      and an alternative view.

PMID- 11442145
TI  - Valproate and the polycystic ovarian syndrome: final thoughts.

PMID- 11442146
TI  - Classification of epileptic disorders.

PMID- 11442147
TI  - Idiopathic generalized epilepsy with generalized and other seizures in
      adolescence.

PMID- 11442148
TI  - Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid,
      in mice.
AB  - PURPOSE: The purpose of this study was to evaluate in mice the anticonvulsant
      potential of N-palmitoylethanolamide, a putative endocannabinoid that accumulates
      in the body during inflammatory processes. METHODS: N-palmitoylethanolamide was
      injected intraperitoneally (i.p.) in mice and evaluated for anticonvulsant
      activity [in maximal electroshock seizure (MES) and chemical-induced convulsions]
      and for neurologic impairment (rotorod). It was compared with anandamide and with
      different palmitic acid analogues as well as with reference anticonvulsants
      (AEDs) injected under the same conditions. RESULTS: The MES test showed, after
      i.p. administration to mice, that N-palmitoy]ethanolamide had an median effective
      dose (ED50) value comparable to that of phenytoin (PHT; 8.9 and 9.2 mg/kg,
      respectively). In the subcutaneous pentylenetetrazol test and in the 3
      mercaptropropionic acid test, it was effective only against tonic convulsions. N
      palmitoylethanolamide was devoid of neurologic impairment < or = 250 mg/kg,
      yielding a high protective index. CONCLUSIONS: N-palmitoylethanolamide, an
      endogenous compound with antiinflammatory and analgesic activities, is a potent
      AED in mice. Its precise mechanism of action remains to be elucidated.

PMID- 11442149
TI  - Neurosteroid withdrawal model of perimenstrual catamenial epilepsy.
AB  - PURPOSE: Perimenstrual catamenial epilepsy, the increase in seizure frequency
      that some women with epilepsy experience near the time of menstruation, may in
      part be related to withdrawal of the progesterone metabolite allopregnanolone, an
      endogenous anticonvulsant neurosteroid that is a potent positive allosteric gamma
      aminobutyric acidA (GABA(A)) receptor modulator. The objective of this study was
      to develop an animal model of perimenstrual catamenial epilepsy for use in
      evaluating drug-treatment strategies. METHODS: A state of prolonged high serum
      progesterone (pseudopregnancy) was induced in 26-day-old female rats by
      sequential injection of pregnant mares' serum gonadotropin and human chorionic
      gonadotropin. Neurosteroid withdrawal was induced by treatment with finasteride
      (100 mg/kg, i.p.), a 5alpha-reductase inhibitor that blocks the conversion of
      progesterone to allopregnanolone. Plasma progesterone and allopregnanolone levels
      were measured by gas chromatography/electron capture negative chemical ionization
      mass spectrometry. Seizure susceptibility was evaluated with the convulsant
      pentylenetetrazol (PTZ). RESULTS: Plasma allopregnanolone levels were markedly
      increased during pseudopregnancy (peak level, 55.1 vs. control diestrous level,
      9.3 ng/mL) and were reduced by 86% 24 h after finasteride treatment (6.4 ng/mL).
      Progesterone levels were unaffected by finasteride. After finasteride-induced
      withdrawal, rats showed increased susceptibility to PTZ seizures. There was a
      significant increase in the number of animals exhibiting clonic seizures when
      challenged with subcutaneous PTZ (60 mg/kg) compared with control pseudopregnant
      animals not undergoing withdrawal and nonpseudopregnant diestrous females. The
      CD50 (50% convulsant dose) was 46 mg/kg, compared with 73 mg/kg in nonwithdrawn
      pseudopregnant animals and 60 mg/kg in diestrous controls. The threshold doses
      for induction of various seizure signs, measured by constant intravenous infusion
      of PTZ, were reduced by 30-35% in neurosteroid-withdrawing animals compared with
      control diestrous females. No change in threshold was observed in pseudopregnant
      rats treated from days 7 to 11 with finasteride, demonstrating that high levels
      of progesterone alone do not alter seizure reactivity. CONCLUSIONS: Neurosteroid
      withdrawal in pseudopregnant rats results in enhanced seizure susceptibility,
      providing an animal model of perimenstrual catamenial epilepsy that can be used
      for the evaluation of new therapeutic approaches.

PMID- 11442150
TI  - Enhanced anticonvulsant activity of neuroactive steroids in a rat model of
      catamenial epilepsy.
AB  - PURPOSE: Perimenstrual catamenial epilepsy may in part be due to withdrawal of
      the endogenous progesterone-derived neurosteroid allopregnanolone that
      potentiates gamma-aminobutyric acidA (GABA(A)) receptor-mediated inhibition. Here
      we sought to determine whether the anticonvulsant potencies of neuroactive
      steroids, benzodiazepines, phenobarbital (PB), and valproate (VPA) are altered
      during the heightened seizure susceptibility accompanying neurosteroid withdrawal
      in a rat model of perimenstrual catamenial epilepsy. METHODS: Test drugs were
      evaluated for their ability to alter the convulsant activity of pentylenetetrazol
      (PTZ) in young adult female rats, in pseudopregnant rats with prolonged exposure
      to high levels of progesterone (and its neurosteroid metabolites), and in
      pseudopregnant rats 24 h after acute withdrawal of neurosteroids by treatment
      with the 5alpha-reductase inhibitor finasteride. Test drugs were administered at
      doses equivalent to twice their ED50 values for protection against PTZ-induced
      clonic seizures in naive young adult female rats. RESULTS: The anticonvulsant
      activity of allopregnanolone (5 mg/kg, s.c.), pregnanolone (5 mg/kg, s.c.),
      allotetrahydrodeoxycorticosterone (15 mg/kg, s.c.), and
      tetrahydrodeoxycorticosterone (10 mg/kg, s.c.) were enhanced by 34-127% after
      neurosteroid withdrawal. The anticonvulsant activity of PB (65 mg/kg, i.p.) was
      also enhanced by 24% in neurosteroid-withdrawn animals. In contrast, the
      anticonvulsant activity of diazepam (4 mg/kg, i.p.), bretazenil (0.106 mg/kg,
      i.p.), and VPA (560 mg/kg, i.p.) were reduced or unchanged in neurosteroid
      withdrawn animals. CONCLUSIONS: The anticonvulsant activity of neuroactive
      steroids is potentiated after neurosteroid withdrawal, supporting the use of such
      agents in the treatment of perimenstrual catamenial epilepsy.

PMID- 11442151
TI  - Enhanced calcium influx in hippocampal CA3 neurons of spontaneously epileptic
      rats.
AB  - PURPOSE: The spontaneously epileptic rat (SER: tm/tm, zi/zi) shows both absence
      like seizures and tonic convulsions. Our previous electrophysiologic studies have
      demonstrated that SER has abnormal excitability of hippocampal CA3 neurons, which
      shows a long-lasting depolarization shift by a single stimulation of mossy
      fibers, probably resulting from the Ca2+ channel abnorrmalities. The present
      study was performed to determine whether Ca2+ influx is actually enhanced in the
      CA3 area of SER. METHODS: Hippocampal slices were prepared from normal Wistar
      rats and SER aged 11-16 weeks old, when the epileptic seizures had been observed,
      and loaded with fura-2AM. Intracellular Ca2+ concentration ([Ca2+]i) was
      monitored as the ratio of fluorescence intensities excited at wavelengths of 340
      and 380 nm (RF340/F380) with photometric devices. RESULTS: High K+ (10-60 mM)
      applied to the bath for 2 min increased [Ca2+]i in hippocampal CA1, CA3, and
      dentate gyrus (DG) areas of both the normal rats and SER in a concentration
      dependent manner. However, the high K+-induced increase in [Ca2+]i was
      significantly more pronounced in the CA3 area of the SER than in that of the
      normal animals, whereas there were no significant differences in high K+-induced
      increases of [Ca2+]i in CA1 or DG between the SER and controls. The high K+
      induced increases in [Ca2+]i of CA1, CA3, and DG were inhibited by nifedipine (1
      to approximately 10 nM), a Ca2+ channel antagonist in both SER and controls.
      However, the inhibition of the high K+-induced increase in [Ca2+]i by nifedipine
      (1 nM) was significantly greater in the CA3 area of SER than that of controls.
      CONCLUSIONS: These findings suggest that Ca2+ influx through the L-type Ca2+
      channels is much greater in the CA3 area of SER than in that of normal animals
      and is involved in the epileptic seizures of the SER.

PMID- 11442152
TI  - Absence epilepsy with fast rhythmic discharges during sleep: an intermediary form
      of generalized epilepsy?
AB  - PURPOSE: To describe a particular form of absence epilepsy (AE) characterized by
      an atypical EEG pattern (fast rhythmic discharges) during sleep and an
      unfavorable course with the persistence of seizures at a late age and drug
      resistance. METHODS: We reviewed the medical files of 31 patients diagnosed with
      AE at our institution been 1995 and 1999 for whom an EEG during sleep had been
      recorded. Patients with fast rhythmic discharges during sleep were selected for
      the study. RESULTS: Five patients showed the usual criteria of childhood absence
      epilepsy (CAE) or juvenile absence epilepsy (JAE), but with fast discharges of
      rhythmic spikes (10-15 Hz) during sleep. such as those typically observed in
      Lennox-Gastaut syndrome. Four patients were of adult age at the time of the last
      examination. Intellectual capacities were "borderline" in each case, with visible
      social and learning handicaps. Absences were the initial seizure event in all
      patients, but four patients developed generalized tonic-clonic seizures during
      the course of the disease. Treatment using a combination of antiabsence drugs
      such as valproate and lamotrigine led to only marginal improvement. CONCLUSIONS:
      These findings illustrate the utility of sleep EEG in detecting the fast rhythmic
      discharges that are markers of drug resistance in AE and suggest the existence of
      transitional forms of AE that are intermediate between idiopathic and
      cryptogenic/symptomatic generalized epilepsies.

PMID- 11442153
TI  - Does the cause of localisation-related epilepsy influence the response to
      antiepileptic drug treatment?
AB  - PURPOSE: We investigated the response to antiepileptic drug (AED) therapy in
      patients with localisation-related epilepsy associated with different underlying
      causes. METHODS: Five hundred and fifty adolescent and adult patients who had
      partial epilepsy treated with AEDs and who had undergone magnetic resonance
      imaging of brain were followed up prospectively from 1984 at a single centre.
      More than 70% were newly diagnosed. None had had epilepsy surgery. RESULTS: Three
      hundred and twelve (57%) patients had been seizure free at their last clinic
      visit for at least a year. Patients with mesial temporal sclerosis (MTS; n = 73,
      42% seizure free) were less likely to be controlled (p < 0.01) than were those
      with arteriovenous malformation (AVM; n = 14, 78%), cerebral infarction (n = 46,
      67%), primary tumour (n = 35, 63%), cortical gliosis (n = 81, 57%), cerebral
      atrophy (n = 49, 55%), and cortical dysplasia (CD; n = 63, 54%). Among the
      seizure-free patients, those with MTS were more likely to require more than one
      AED compared with those with other aetiologies (48 vs. 35%; p < 0.05). There was
      no difference in outcome between patients with symptomatic and cryptogenic
      epilepsy (n = 361, 58% vs. n = 189, 56% seizure free, respectively). Patients
      with MTS, CD, and cryptogenic epilepsy were more likely (p = 0.02) to have a
      family history of epilepsy than were the other groups. MTS patients also had a
      higher incidence of febrile convulsions (p < 0.001). CONCLUSIONS: The majority of
      patients with focal-onset epilepsy became seizure free on AED treatment. MTS
      related seizures had the worst prognosis. Although many patients with this
      pathology may benefit from epilepsy surgery, a considerable number will be
      controlled with AED therapy.

PMID- 11442154
TI  - Relevance of residual histologic and electrocorticographic abnormalities for
      surgical outcome in frontal lobe epilepsy.
AB  - PURPOSE: To estimate the significance of residual electrocorticographic and
      neuropathologic abnormalities on seizure control after surgery for frontal lobe
      epilepsy with the purpose of determining their relevance in deciding the extent
      of the surgical procedure. METHODS: The presence of epileptiform discharges in
      intraoperative electrocorticograms (ECoGs) and the nature and extent of
      neuropathologic abnormalities were reviewed for 35 patients who underwent frontal
      lobe resections for the treatment of epilepsy at our institution. The relations
      between surgical outcome and presence of the following features were studied: (a)
      presence of abnormal tissue at the limits of the resection; (b) presence of
      sporadic spikes and seizure patterns in the preresection ECoG; (c) their
      abolition in the postresection ECoG; and (d) the topography of residual
      discharges with respect to the margins of the resection. RESULTS: On
      neuropathologic examination, 18 patients showed focal cortical dysplasia (CD),
      and 17 showed other abnormalities (non-CD). Ten CD patients and 11 non-CD
      patients experienced a favourable outcome. Seizure patterns were significantly
      more common in patients with focal cortical dysplasia than in those without, with
      a sensitivity of 94% and a specificity of 75%. Abolition of seizure patterns was
      associated with a favourable surgical outcome (p = 0.031). Abolition of sporadic
      spikes or their presence in the postresection ECoG did not influence outcome.
      There was no clear relation between outcome and location of residual sporadic
      discharges. Seizure patterns persisted in the postresection ECoG in three CD
      patients, were located at the margins of the resection in all three, and these
      patients had a poor outcome. Incomplete removal of abnormal tissue was not
      associated with a poorer outcome in either patient group or in the complete
      sample. CONCLUSIONS: Seizure patterns were significantly more common in patients
      with cortical dysplasia, and their abolition on postresection ECoG recordings was
      associated with a favourable surgical outcome. Persistence of sporadic ECoG
      spikes and incomplete removal of histologic abnormalities did not affect outcome
      significantly.

PMID- 11442155
TI  - Status epilepticus and tiagabine therapy: review of safety data and epidemiologic
      comparisons.
AB  - PURPOSE: To determine whether an increased risk of status epilepticus (SE) and
      complex partial status epilepticus (CPSE) is associated with tiagabine (TGB)
      therapy. METHODS: Thirteen cases in which an EEG, performed on patients with
      altered mental status taking TGB, was reported to demonstrate spike-and-wave
      discharges (SWDs) were reviewed by a panel of experts. In addition, all cases of
      suspected SE from TGB clinical trials were reviewed. The occurrence of SE in four
      epidemiologic cohorts from Rochester, Minnesota, Turku, Finland, Bronx, New York,
      and New Haven, Connecticut was analyzed as an external comparison. RESULTS:
      Review of the 13 cases with reported SWDs found that the majority had had prior
      EEGs with similar findings, and only three were thought to have electrographic
      evidence of SE. There was no difference in the frequency of SE or CPSE in the
      placebo-controlled clinical trials between the TGB-treated (1.0% SE, 0.8% CPSE)
      and placebo-treated (1.5% SE, 1.5% CPSE) groups. The 5% frequency of SE and 3%
      frequency of CPSE in the TGB-treated patients in the long-term safety studies,
      which included 2,248 patients, were very similar to the rates of occurrence of SE
      and CPSE in the four external cohorts. The major risk factor for the occurrence
      of SE and CPSE in all groups was a prior episode of SE (p < 0.0001). CONCLUSIONS:
      Over a 3-year period, SE will occur in 5-10% of patients with epilepsy not in
      remission. At highest risk are those who have had a prior episode of SE.
      Treatment with TGB in recommended doses does not increase the risk of SE in
      patients with partial seizures.

PMID- 11442156
TI  - Propofol and midazolam in the treatment of refractory status epilepticus.
AB  - PURPOSE: To explore outcome differences between propofol and midazolam (MDL)
      therapy for refractory status epilepticus (RSE). METHODS: Retrospective chart
      review of consecutive patients treated for RSE between 1995 and 1999. RESULTS: We
      found 14 patients treated primarily with propofol and six with MDL. Propofol and
      MDL therapy achieved 64 and 67% complete clinical seizure suppression, and 78 and
      67% electrographic seizure suppression, respectively. Overall mortality, although
      not statistically significant, was higher with propofol (57%) than with MDL (17%)
      (p = 0.16). Subgroup mortality data in propofol and MDL patients based on APACHE
      II (Acute Physiology and Chronic Health Evaluation) score did not show
      statistically significant differences except for propofol-treated patients with
      APACHE II score > or = 20, who had a higher mortality (p = 0.05). Reclassifying
      the one patient treated with both agents to the MDL group eliminated this
      statistically significant difference (p = 0.22). CONCLUSIONS: In our small sample
      of RSE patients, propofol and MDL did not differ in clinical and electrographic
      seizure control. Seizure control and overall survival rates, with the goal of
      electrographic seizure elimination or burst suppression rather than latter alone,
      were similar to previous reports. In RSE patients with APACHE II score > or = 20,
      survival with MDL may be better than with propofol. A large multicenter,
      prospective, randomized comparison is needed to clarify these data. If comparable
      efficacy of these agents in seizure control is borne out, tolerance with regard
      to hemodynamic compromise, complications, and mortality may dictate the choice of
      RSE agents.

PMID- 11442157
TI  - Topiramate and metabolic acidosis in pediatric epilepsy.
AB  - PURPOSE: Topiramate (TPM) has been widely used as an adjunctive therapy for
      treating epilepsy. TPM is reported to have multiple mechanisms of action,
      including inhibition of carbonic anhydrase, which may result in metabolic
      acidosis from decreased serum bicarbonate (HCO3-). METHODS: Clinical data from 30
      children who received TPM as adjunctive therapy for medically refractory epilepsy
      were reviewed at Children's Hospital, Boston. Serum HCO3- levels were assessed
      before, during, and after discontinuing TPM (n = 9). When multiple data were
      available, mean values were used for analysis. RESULTS: Of the 30 patients, 21
      had a >10% decrease in HCO3- levels. The mean decrease in HCO3- among the 21
      patients was 4.7 mEq/L, and maximum was 10 mEq/L. No clinical symptoms occurred,
      and HCO3- supplement was not needed, except for one patient who developed
      tachypnea from worsened acidosis after prolonged status epilepticus during a
      suspected viral illness. Among the 21 patients, TPM was discontinued in seven
      children because of a lack of efficacy, and in two because of anorexia. After
      discontinuing TPM, the serum HCO3- returned to the previous level before starting
      TPM in all nine. CONCLUSIONS: Decreased HCO3- levels occurred in the majority of
      patients reviewed, usually only to a small to moderate extent, but by 8 and 10
      mEq/L in two cases. In patients at risk for acidosis, the decrease in HCO3- may
      cause significant consequences, such as severe acidosis or renal calculi.
      Monitoring HCO3- levels before and during TPM therapy may be indicated,
      especially with conditions that predispose to acidosis.

PMID- 11442158
TI  - Photosensitivity in relation to epileptic syndromes: asurvey from an epilepsy
      center in Japan.
AB  - PURPOSE: We examined the incidence and distribution of photosensitivity among the
      different age groups and different types of epilepsies and epileptic syndromes.
      Furthermore, we considered the influence of ethnic and geographic factors on the
      incidence of photoparoxysmal response (PPR) in epilepsy patients. METHODS: We
      analyzed the responses to intermittent photic stimulation (IPS) by using a Grass
      PS22 or PS33 photic stimulator for in 2,187 unselected patients with epilepsy who
      were treated in our center. RESULTS: The classic PPR was elicited in 37 (1.7%)
      patients. The mean age of these 37 patients was 17.0 years. The subpopulation of
      patients having PPR included 2.0% of all patients with symptomatic generalized
      epilepsy. 5.6% (p < 0.01) of those with idiopathic generalized epilepsy, 0.7% of
      those with symptomatic localization-related epilepsy, and 2.9% of those with
      undetermined epilepsy. PPR accounted for 17.4% (p < 0.01) of the patients with
      juvenile myoclonic epilepsy, 7.6% (p < 0.01) of those with grand mal on
      awakening, and 6.1% (p < 0.01) of those with symptomatic occipital lobe epilepsy.
      The incidence of PPR increased in patients up to age 15 years, and suddenly
      decreased after age 20 years. CONCLUSION: The present study presents the first
      report from eastern Asia, analyzing the incidence of PPR with a restricted
      definition comparable to the other studies, and the rate of PPR was relatively
      low compared with the studies performed in the European countries. We could
      confirm the clear relation between age and positive PPR.

PMID- 11442159
TI  - Clinical features and prognosis of nonepileptic seizures in a developing country.
AB  - PURPOSE: To determine the predictive value of clinical features and medical
      history in patients with nonepileptic seizures (NESs). METHODS: One hundred sixty
      one consecutive ictal video-EEGs were reviewed, and 17 patients with 41 NESs
      identified. NES diagnosis was defined as paroxysmal behavioral changes suggestive
      of epileptic seizures recorded during video-EEC without any electrographic ictal
      activity. Clinical features, age, sex, coexisting epilepsy, associated
      psychiatric disorder, social and economic factors, delay in reaching the
      diagnosis of NES, previous treatment, and correlation with outcome on follow-up
      were examined. RESULTS: The study population included 70% female patients with a
      mean age of 33 years. Mean duration of NESs before diagnosis was 9 years. Forty
      one percent had coexisting epilepsy. The most frequent NES clinical features were
      tonic-clonic mimicking movements and fear/anxiety/hyperventilation. The most
      common psychiatric diagnosis was conversion disorder and dependent and borderline
      personality disorder. Seventy-three percent of patients with pure NESs received
      antiepileptic drugs (AEDs), and 63.5% of this group received new AEDs. Fifty-nine
      percent of the patients received psychological/psychiatric therapy. At follow-up,
      23.5% were free of NESs. CONCLUSIONS: All seizure-free patients had two good
      prognostic factors: having an independent lifestyle and the acceptance of the
      nonepileptic nature of the episodes. Video-EEG monitoring continues to be the
      diagnostic method to ensure accurate seizure classification. Establishing
      adequate health care programs to facilitate access to new technology in public
      hospitals as well as the implementation of continuous education programs for
      general practitioners and neurologists could eventually improve the diagnosis and
      treatment of patients with NESs.

PMID- 11442160
TI  - Lateralized postictal EEG delta predicts the side of seizure surgery in temporal
      lobe epilepsy.
AB  - PURPOSE: The concordance of lateralized EEG postictal polymorphic delta activity
      (PPDA) to the side of seizure origin in temporal lobe epilepsy (TLE) has received
      limited study. Our objective was to study the lateralizing value of PPDA in
      patients with documented TLE. METHODS: A cohort of consecutive adults with TLE,
      detailed presurgical evaluation before temporal lobectomy, and minimal follow-up
      of 2 years were included. One author masked the ictal rhythm of presurgical EEGs
      and randomly presented 20 s of preictal and the postictal EEG to two
      electroencephalographers who were blind to all clinical data. They independently
      assigned PPDA to one of three categories: not present, bilateral, or lateralized
      (defined as newly appearing or an amplitude >50% of the preictal record).
      RESULTS: Eighty seizures from 29 patients were studied. Fifteen patients had a
      left, and 14 had a right temporal lobectomy. Twenty-three patients were seizure
      free or substantially improved (defined as simple partial or nocturnal seizures
      only). Lateralized PPDA was present in 64% of all EEGs and at least one record
      from 22 (76%) patients. Lateralized PPDA, when present, was concordant with the
      side of surgery in 96% of the EEGs. CONCLUSIONS: Lateralized PPDA is highly
      predictive of the side of ultimate temporal lobectomy, and by inference the side
      of seizure origin.

PMID- 11442161
TI  - Modification of slow cortical potentials in patients with refractory epilepsy: a
      controlled outcome study.
AB  - PURPOSE: To compare self-regulation of low-frequency EEG components (slow
      cortical potentials, SCPs) with other methods of seizure control for patients
      with drug-refractory partial epilepsy and to separate the real anticonvulsive
      effect from placebo effects. METHODS: Results of a treatment program of SCP self
      regulation (experimental group) are compared with two groups of patients, one of
      which learned self-control of respiratory parameters (end-tidal CO2 and
      respiration rate: RES group); the other received medication with new
      anticonvulsive drugs (AEDs) in combination with psychosocial counseling (MED
      group). Clinical, cognitive, behavioral, and personality measures were assessed
      before and after treatment. In addition, to control for placebo responses,
      patients repeatedly estimated their beliefs in the efficiency of the respective
      treatment, their satisfaction and expectations, and the quality of the
      relationship with their therapists. RESULTS: SCP and MED groups showed a
      significant decrease of seizure frequency, but the RES group did not. Clear
      positive changes in the sociopsychological adjustment were obtained in all three
      groups, with the maximal improvement being attained in the RES group.
      CONCLUSIONS: All kinds of therapy result in considerable improvement of patients'
      emotional state, which may in part be due to potential placebo effects: however,
      this improvement is not related to the quality of the therapeutic effect proper
      (i.e., seizure reduction). Traditional double-blind control group designs are
      inappropriate for behavioral interventions or treatments with psychoactive
      pharmacologic drugs. Rather, specific tests can be developed to control the
      placebo effect and to separate it from the genuine therapeutic effects.

PMID- 11442162
TI  - Correlation of scalp EEG and 1H-MRS metabolic abnormalities in temporal lobe
      epilepsy.
AB  - PURPOSE: To correlate the interictal spike field and region of seizure onset with
      the distribution of 1H-MRS abnormalities in temporal lobe epilepsy (TLE) and
      improve our understanding of the clinical significance of 1H-MRS abnormalities.
      METHODS: Scalp electroencephalogram (EEG) monitoring and proton magnetic
      resonance spectroscopy (1H-MRS) results were correlated in 31 consecutive
      patients with TLE. RESULTS: Lateralized 1H-MRS-based hippocampal abnormalities
      were recorded in 95% of the patients with unilateral interictal spikes, with a
      high degree of concordance for the lateralization side (90%). In 64% of the
      patients with normal or bilateral interictal EEG spikes, 1H-MRS provided
      lateralizing information. Bilateral 1H-MRS abnormalities, with or without
      lateralization, were 3 times more frequent than bitemporal EEG spikes. Anterior
      predominance of the 1H-MRS abnormalities was more frequent in patients with
      anterior temporal EEG spiking (50%), than in patients without this EEG
      distribution (18%). Similar association was noted between distribution of 1H-MRS
      abnormalities and region of EEG seizure onset. CONCLUSIONS: Our results show a
      moderate level of concordance between the distribution of 1H-MRS and EEG
      abnormalities. 1H-MRS identifies abnormalities contralateral to the predominant
      seizure focus more often than does EEG and may provide lateralizing information
      in patients with nonlateralizing interictal EEG.

PMID- 11442163
TI  - The effect of vagus nerve stimulation on epileptiform activity recorded from
      hippocampal depth electrodes.
AB  - PURPOSE: To assess the effect of vagus nerve stimulation (VNS) on interictal
      epileptiform activity in the human hippocampus. Clinical studies have established
      the efficacy of vagus nerve stimulation in patients with epilepsy (VNS Study
      Group, 1995), although the electrophysiologic effects of VNS on the human
      hippocampus and mesial temporal lobe structures remain unknown. METHODS: We
      report a case study in which a patient with an implanted VNS underwent
      intracranial electrode recording before temporal lobectomy for intractable
      complex partial seizures. Epileptiform spikes and sharp waves were recorded from
      a depth electrode placed in the patient's left hippocampus. Spike frequencies and
      sharp-wave frequencies before and during VNS were compared using both a 5- and a
      30-Hz stimulus. Different stimulation rates were tested on different days, and
      all analyses were performed using a Student's t test. RESULTS: We found no
      significant differences in spike frequency between baseline periods and
      stimulation at 5 and 30 Hz. In contrast, stimulation at 30 Hz produced a
      significant decrease in the occurrence of epileptiform sharp waves compared with
      the baseline, whereas stimulation at 5 Hz was associated with a significant
      increase in the occurrence of epileptiform sharp waves. CONCLUSIONS: VNS produces
      a measurable electrophysiologic effect on epileptiform activity in the human
      hippocampus. Although a clinical response to VNS did not occur in our patient
      before surgery, 30-Hz VNS suppressed interictal epileptiform sharp waves that
      were similar in appearance to those seen during the patient's actual seizures. In
      contrast, 5-Hz stimulation appeared to increase the appearance of interictal
      sharp waves.

PMID- 11442164
TI  - Unusual imaging findings in progressive myoclonus epilepsy.
AB  - We describe a patient with progressive myoclonus epilepsy (PME), white matter
      hyperintensities in the corpus callosum, cerebral hemispheres, and left cerebral
      peduncle on magnetic resonance imaging (MRI), and positive oligoclonal bands. A
      phosphorus magnetic resonance spectrum was compatible with mitochondrial
      dysfunction. Abnormal white matter signals are not a feature of the known PME
      syndromes, although they occur in Leber's hereditary optic neuropathy (LHON).
      These abnormalities oriented the diagnosis toward mitochondrial disease.

PMID- 11442165
TI  - Induction of hypersensitivity to a previously tolerated antiepileptic drug by a
      second antiepileptic drug.
AB  - PURPOSE: To describe the induction of hypersensitivity to one antiepileptic drug
      (AED) by a second AED. METHODS: Case report and review of the relevant
      literature. RESULTS: A patient is reported who was treated with phenytoin (PHT)
      for 6 months without adverse effect, but developed a hypersensitivity reaction
      with rash, fever, elevated liver enzymes, lymphadenopathy, and colitis 6 weeks
      after the introduction of carbamazepine (CBZ). PHT and CBZ were discontinued.
      Seizures continued despite treatment with valproic acid and clobazam. A decision
      was made to cautiously reintroduce PHT. Diffuse skin rash and pharyngitis
      appeared after two doses of PHT. CONCLUSIONS: The AED hypersensitivity syndrome
      has been thought to occur as a consequence of preexisting pharmacogenetic and
      immunologic abnormalities. Our case demonstrates induction of hypersensitivity to
      an AED that had been formerly well tolerated, after a hypersensitivity reaction
      to another AED. This is distinct from simple cross-reactivity between one or more
      drugs. Such induction of hypersensitivity with AEDs has not been previously
      described.

PMID- 11442166
TI  - Cryptogenic epilepsy: an infectious etiology?
AB  - PURPOSE: Cryptogenic epilepsy, the group of epilepsy syndromes for which an
      etiology is unknown, comprises approximately 20% of all epilepsy syndromes. We
      selected patients in this subgroup of epilepsy and tested them for evidence of
      Toxoplasma gondii IgG antibodies by the enzyme-linked immunosorbent assay. T.
      gondii is found in up to 20% of the U.S. population forming dormant brain cysts
      in the latent bradyzoite form. We investigated the hypothesis that dormant T.
      gondii infection might be associated with cryptogenic epilepsy. METHODS: We
      selected patients with cryptogenic epilepsies and tested them for evidence of T.
      gondii IgG antibodies by the enzyme-linked immunosorbent assay. A control group
      was also tested for comparison. RESULTS: We have found a statistically
      significant elevation of T. gondii antibodies among cryptogenic epilepsy patients
      as compared to controls [59% increase in optical density (OD), p = 0.013]. This
      association persisted after adjustment for subjects' gender and age in a multiple
      logistic regression model; however, it was no longer as statistically
      significant. CONCLUSIONS: Our results suggest that chronic T. gondii infection
      with brain cysts may be a cause of cryptogenic epilepsy.

PMID- 11442167
TI  - Developed versus undeveloped conditions in the management of epilepsy: advantages
      and disadvantages.

PMID- 11442168
TI  - Prosaposin-derived peptides enhanced sprouting of sensory neurons in vitro and
      induced sprouting at motor endplates in vivo.
AB  - Prosaposin exhibits neurotrophic factor properties that are localized to a 12
      amino acid sequence located in the amino terminal portion of the saposin C
      domain. Prosaptides are peptides derived from the neurotrophic portion of
      prosaposin; these have been previously reported to be bioactive in neuroblastoma
      cell lines in vitro. We report that prosaptides were also bioactive in explants
      of adult primary sensory neurons by dose-dependently increasing both the number
      (3- to 4-fold) and elongation of these neurites by 50%. Local injection of
      prosaptides into the gluteus muscle of adult mice also induced sprouting at the
      motor endplate. Our results indicate that prosaptides are potent neuritogenic
      factors for both sensory and motor neurons of adult peripheral nerve.

PMID- 11442169
TI  - Complement activation in acquired and hereditary amyloid neuropathy.
AB  - The pathogenesis of the axonal degeneration in acquired or hereditary amyloidosis
      is unknown. In this immunohistochemistry study, we examined 20 sural nerve
      biopsies from individuals with amyloid neuropathy (14 acquired and 6 hereditary)
      for evidence of complement activation. Complement activation products were
      detected on and around amyloid deposits within peripheral nerves. We found no
      difference in the extent, location or pattern of complement activation products
      between the 2 forms of amyloidosis. The presence of early classical pathway
      activation markers in the absence of antibody in hereditary cases suggests an
      antibody-independent activation of the classical pathway through binding of C1q.
      The lack of Factor Bb-suggested alternative pathway activation was not
      significant in these cases. The detection of C5b-9 neoantigen on amyloid deposits
      demonstrated that the full complement cascade was activated. Complement
      activation on amyloid deposits and the generation of C5b-9 in vivo may contribute
      to bystander injury of axons in the vicinity of amyloid deposits.

PMID- 11442170
TI  - Detection of host and donor cells in sex-mismatched rat nerve allografts using RT
      PCR for a Y chromosome (H-Y) marker.
AB  - The donor and host source of support cells, such as Schwann cells, in nerve
      allograft segments have been the subject of debate. The objective of the present
      study was to assess the utility of a molecular technique that probes for a Y
      chromosome expressed gene (H-Y) in distinguishing host from donor tissue in sex
      mismatched nerve allograft segments. Forty-two Lewis rats received bilateral
      syngeneic Lewis or allogeneic ACI rat peroneal nerve grafts, with or without
      cyclosporin A (CsA) treatment. At different times thereafter animals were
      sacrificed and samples were harvested. We transplanted males and females
      reciprocally, to study both survival of donor cells (persisting H-Y mRNA in male
      grafts by transcription polymerase chain reaction (RT-PCR), and graft
      infiltration by host cells (detectable H-Y mRNA in female grafts). A kinetic
      analysis revealed a progressive loss of viable donor cells (loss of H-Y mRNA
      signal) from allografts, beginning 2-3 weeks, and culminating at 4 weeks, with
      little detectable H-Y in the absence of CsA treatment. CsA treatment led to
      prolonged survival of allograft cells, confirmed by detectable H-Y mRNA. By
      studying female grafts in male rats we could confirm that loss of viable donor
      tissue in allografts was accompanied by infiltration of host (H-Y mRNA positive)
      cells, whereas no H-Y mRNA signal was seen in males receiving autografts from
      females or in immunosuppressed allograft segments. These data suggest that
      reverse RT-PCR analysis for a Y chromosome gene product can be a valuable tool to
      assess the origin of viable cells in sex-mismatched nerve allotransplantation
      tissue.

PMID- 11442171
TI  - Hereditary motor and sensory neuropathy with absence of large myelinated fibers
      due to absence of large neurons in dorsal root ganglia and anterior horns,
      clinically associated with deafness, mental retardation, and epilepsy (HMSN-ADM).
AB  - Hereditary motor and sensory neuropathy (HMSN) with autosomal recessive
      inheritance represents a genetically heterogeneous group of disorders with
      variable clinical, pathologic and electrophysiologic manifestations. A new
      variant of autosomal recessive HMSN, clinically defined by sensorimotor
      polyneuropathy associated with deafness and mental retardation, has recently been
      described. We report on the first autopsy case with this type of HMSN: a girl of
      non-consanguineous parents with a presumably autosomal recessive type of motor
      and sensory neuropathy clinically associated with deafness, mental retardation,
      and epilepsy. The autopsy showed complete absence of large myelinated fibers in
      peripheral motor and sensory nerves corresponding to a lack of large neurons in
      dorsal root ganglia and anterior horns of the spinal cord, moderate neurogenic
      muscle atrophy, and nearly complete absence of neurons in the dentate nucleus of
      the cerebellum. Molecular genetic analyses in our case revealed neither genetic
      alterations in the survival motor neuron gene nor in the PMP-22 gene.

PMID- 11442172
TI  - Chronic inflammatory demyelinating polyneuropathy caused by HIV infection in a
      patient with asymptomatic CMT 1A.
AB  - It is well known that patients with Charcot-Marie-Tooth (CMT) disease are liable
      to present with episodes of cortisone-responsive demyelination, and a
      superimposed inflammatory component has been suggested. We report a patient who
      presented with a chronic inflammatory demyelinating polyneuropathy due to a
      recent HIV infection, which revealed a previously asymptomatic CMT 1A disease
      documented by identification of the characteristic duplication on the p11.2
      region of chromosome 17. The inflammatory process was characterized by pathologic
      findings on a superficial peroneal nerve biopsy, and the patient improved
      significantly after corticotherapy. This report gives support to the hypothesis
      of a genetic susceptibility to inflammatory demyelinating processes in certain
      CMT kindreds.

PMID- 11442173
TI  - Intraneural nerve metastasis with multiple mononeuropathies.
AB  - Although cancer is a frequent condition, neoplastic involvement of the peripheral
      nervous system is rare. The mechanisms are heterogeneous and include lesions
      within the cerebrospinal fluid (CSF) space, local invasion (e.g. brachial
      plexus), compression, rarely direct infiltration, perineurial spread and even
      rarer intranerval metastasis. A 47-year-old woman had been treated for a
      carcinoid 10 years earlier and had received axillar irradiation. At presentation
      she suffered from weakness of the biceps brachii and was experiencing pain
      radiating from the axilla into the forearm and thumb. MR scans of the brachial
      plexus were negative and her symptoms were primarily considered to stem from a
      postradiation brachial plexopathy, Because of increasing pain, the brachial
      plexus was explored and a metastasis in the left musculocutaneous nerve was
      resected. Several months later, numbness and pain appeared in the ulnar nerve and
      another intrafascicular metastasis in the ulnar nerve was discovered. Resection
      with preservation of remaining fascicles was performed. This rare case report
      demonstrates that multiple mononeuropathies, resembling multiplex neuropathy, may
      be caused by intranerval metastasis.

PMID- 11442174
TI  - The use of antimetabolites with trabeculectomy: a critical appraisal.
AB  - PURPOSE: To examine why most ophthalmologists routinely use mitomycin C or 5
      fluorouracil (antimetabolites) in association with filtering surgery for
      glaucoma. METHODS: Critical analysis of seven medical, social and economic
      trends. RESULTS: The rapid acceptance of the adjunctive use of antimetabolites at
      the time of filtration surgery may be explained by reasons other than anticipated
      increase in the "success" of glaucoma surgery. CONCLUSION: The use of
      antimetabolites in conjuction with filtering glaucoma surgery may be at least
      partially a consequence of changing medical-social-economic factors, rather than
      solely a desire on the part of physicians to improve the "success" of glaucoma
      surgery. This may indicate a need to reevaluate the proper place of
      antimetabolites in association with filtration surgery.

PMID- 11442175
TI  - Hepatocyte growth factor is increased in the aqueous humor of glaucomatous eyes.
AB  - PURPOSE: To assess the concentrations of hepatocyte growth factor (HGF) in the
      aqueous humor of eyes with glaucoma compared with control eyes with cataract
      only. METHODS: Concentrations of HGF were measured in aqueous humor aspirates
      taken during anterior segment surgery from 84 patients, of whom 72 had glaucoma
      (38 cases of primary open-angle glaucoma, 17 angle-closure glaucoma, and 17
      exfoliative glaucoma) and 12 had cataract only, using a sandwich enzyme-linked
      immunosorbent assay kit. RESULTS: Hepatocyte growth factor was detected in all
      samples. The concentration in eyes with cataract only was 563.3 +/- 178.8 pg/mL
      (mean +/- standard deviation), which was significantly lower than that in eyes
      with glaucoma (967.1 +/- 514.7 pg/mL, P < 0.01). Eyes with exfoliative glaucoma
      had significantly higher HGF concentrations (1,425.5 +/- 586.7 pg/mL) than did
      eyes with primary open-angle glaucoma (855.0 +/- 341.5 pg/mL) and angle-closure
      glaucoma (759.4 +/- 511.4 pg/mL) (P < 0.01). There was no effect of age, sex, or
      history of medical, laser, or surgical treatment on the aqueous humor HGF
      concentration (P > 0.05). Aqueous humor and plasma HGF concentrations were
      measured and compared in 28 patients. The aqueous humor HGF concentration (908 +/
      586.2 pg/mL) was significantly higher (P < 0.01) than the plasma concentration
      (521.3 +/- 183.1 pg/mL). No significant correlation could be found between
      aqueous humor and plasma HGF concentrations. CONCLUSIONS: The relatively high
      concentration of HGF in human aqueous humor suggests that HGF may play an
      important role in ocular physiology and disease. The higher concentration in
      patients with glaucoma may indicate a response to injury.

PMID- 11442176
TI  - Retinal nerve fiber layer and physiological central corneal thickness.
AB  - PURPOSE: To determine the relationship between central corneal thickness and the
      measurement of retinal nerve fiber layer thickness around the optic nerve head
      using a confocal scanning laser polarimeter such as the Nerve Fiber Analyzer
      (GDx). METHODS: Forty-four eyes were recruited for this study. Each patient had a
      normal visual field and a healthy optic nerve head, which was assessed by slit
      lamp biomicroscopy with a 90-diopter lens and by a scanning laser ophthalmoscope
      (Heidelberg Retina Tomograph). Using the GDx, retinal nerve fiber layer thickness
      was calculated from 1.75 disc diameters together with some standard GDx
      parameters, including the number, symmetry, superior ratio, inferior ratio,
      maximum modulation, and ellipse modulation. Corneal thickness was measured with
      the DGH-1000 ultrasonic pachymeter. Descriptive analysis was used and Pearson's r
      coefficient of correlation was calculated. RESULTS: Corneal thickness was not
      significantly correlated to retinal nerve fiber layer thickness, but it was
      significantly (P < 0.05) correlated to the other GDx parameters. CONCLUSION: From
      these data. peripapillary retinal nerve fiber layer thickness is shown not to be
      significantly correlated to the corneal thickness, even if for the standard GDx
      parameters a significant correlation was found.

PMID- 11442177
TI  - Influence of scan radius correction for ocular magnification and relationship
      between scan radius with retinal nerve fiber layer thickness measured by optical
      coherence tomography.
AB  - PURPOSE: To investigate how optical coherence tomography (OCT) modifies the
      preset scan parameters to correct the errors resulting from ocular magnification,
      the influence of examiner's final correction of those already modified parameters
      on retinal nerve fiber layer (RNFL) thickness measurements, the induced change on
      RNFL thickness measurements and RNFL estimated integrals (RNFL(estimated
      integrals)) by adjusting the actual scan radius during RNFL examinations
      performed by OCT. METHODS: Thirty-five healthy patients underwent an RNFL
      examination by OCT four times using different scan radii. The first scan was
      performed with the preset circular scan diameter of 3.46 mm; the actual scan
      diameter was different, however, because it was modified by the OCT instrument.
      The second, third, and fourth scans were generated after readjusting the already
      modified scan diameter by the examiner to 3.46, 3.20, and 3.60 mm. The
      relationship of axial length and refractive error with the actual scan radius
      (with ocular magnification calculated by OCT), with the influence of the
      examiner's final correction on RNFL thickness measurements, with the relationship
      between scan radius with RNFL thickness measurements, and with RNFL(estimated
      integrals) were investigated. RESULTS: The actual scan diameter was found to be
      primarily determined by axial length (R = 0.97, P < 0.0001), but the influence of
      refractive error was small (R = -0.26, P = 0.067). Final correction of the actual
      scan radius by the examiner had a significant influence on RNFL thickness
      measurements (P = 0.025). RNFL thickness measurements obtained without correction
      of the actual scan radius for magnification were found to be inversely correlated
      with axial length (R = -0.54, P = 0.001), whereas no similar relationship was
      found when RNFL thickness measurements were obtained with correction (R = 0.21, P
      = 0.11). A reciprocal relationship between 1/scan radius with RNFL thickness
      measurements (they tended to be thinner as scan radii were increased) was found
      (R = 0.41, P = 0.169), but RNFL(estimated integrals) areas were found to be
      independent of the scan radius (P = 0.521). CONCLUSION: To increase the accuracy
      of RNFL thickness measurements, it will be appropriate for the examiner to
      manually correct the actual scan parameters to the desired or preset ones after
      their automatic modification performed by the OCT instrument. Keeping the actual
      scan radius constant for repeated exams is also recommended because RNFL
      thickness measurements were found to depend on scan size. Alternatively,
      RNFL(estimated integrals) could be used because they were found to be independent
      of the scan size.

PMID- 11442178
TI  - Normal retinal nerve fiber layer thickness in the peripapillary region measured
      by scanning laser polarimetry.
AB  - PURPOSE: To measure retinal nerve fiber layer thickness (RNFLT) as a function of
      distance from the optic nerve head using a confocal scanning laser polarimeter,
      such as the Nerve Fiber Analyzer (GDx). METHODS: Twenty eyes of 20 healthy
      patients were recruited for this study. Each patient had a normal visual field
      and a healthy optic nerve head, which was assessed by slit-lamp biomicroscopy
      using a 90-diopter lens and by a scanning laser ophthalmoscope. Using the GDx,
      RNFLT was calculated from 1.1 disc diameters (DD) to 2.5 DD in 0.1-DD increments
      from the outer edge of the optic disc rim. RNFLT was successively evaluated for
      the entire annulus surface, for each quadrant, and for every 10 degree sector.
      RNFLT was calculated in retardation degrees. Differences in RNFLT were calculated
      by analysis of variance. RESULTS: When the entire RNFLT was considered, the
      measurements close to the optic nerve head (at 1.1 and 1.2 DD) were found to be
      significantly (0.05 < or = P < or = 0.01) different from those measured far from
      the disc (at 2.4 and 2.5 DD). The inferior quadrant had the greatest RNFLT
      followed by the superior quadrant. When RNFLT was analyzed for every 10 degrees,
      RNFLT at 1.1 and 1.2 DD was significantly (P < or = 0.001) different from that
      measured at 2.4 and 2.5 DD in almost all 36 sectors. In the 36 considered
      sectors, no significant difference was found for all the RNFLT values that were
      calculated in all the positions of the annulus surface between 1.1 and 1.7 DD.
      CONCLUSION: From these data, peripapillary RNFLT is shown to be significantly (P
      < or = 0.001) thinner in the periphery (2.5 DD) than around the optic disc (1.1
      DD). However, the lack of any difference in RNFLT from 1.1 to 1.7 DD suggested
      that the mild variations to locate the optic disc contour line do not change the
      results of the analysis if the RNFLT is calculated within 1.8 DD.

PMID- 11442179
TI  - Sleep disorders: a risk factor for normal-tension glaucoma?
AB  - PURPOSE: To determine the prevalence of sleep-related symptoms and sleep-related
      breathing disorders by polysomnography in patients with normal-tension glaucoma
      (NTG). PATIENTS AND METHODS: This comparative case series included 23 patients
      with NTG, 14 NTG suspects, and 30 comparison patients without NTG. A sleep
      history was obtained and determined to be positive or negative. Polysomnography
      was offered for patients with a positive sleep history. Prevalence of a positive
      sleep history and prevalence of sleep disorders were the main outcome measures.
      RESULTS: The NTG, NTG suspect, and comparison groups did not differ with respect
      to age, body mass index, systemic disease, gender, or race. Thirteen (57%) of 23
      patients with NTG, 6 (43%) of 14 NTG suspects, and 1 (3%) of 30 comparison
      patients had a positive sleep history (P = 0.001). Nine of 13 patients with NTG
      and four of six NTG suspects with a positive sleep history chose to undergo
      polysomnography. Seven (78%) of nine patients with NTG and all four NTG suspects
      undergoing polysomnography were diagnosed with a sleep disorder. Five patients
      with NTG had sleep apnea and two had sleep hypopnea. Two NTG suspects had sleep
      apnea; one had sleep hypopnea; and one had upper airway resistance syndrome. The
      one comparison patient with a positive sleep history had upper airway resistance
      syndrome by polysomnography. CONCLUSIONS: Sleep-disturbed breathing may be a risk
      factor for NTG. Although we do not provide evidence for a cause-and-effect
      relationship, various physiologic factors produced by sleep-disturbed breathing
      may play a significant role in the pathogenesis of this optic neuropathy. We
      recommend obtaining a sleep history from patients with NTG and performing
      polysomnography in those patients with sleep disturbance symptoms.

PMID- 11442180
TI  - Resource use and costs of patients with glaucoma or ocular hypertension: a one
      year study based on retrospective chart review in the Netherlands.
AB  - PURPOSE: To estimate resource use and costs associated with the diagnosis and
      treatment of glaucoma and ocular hypertension in the Netherlands in 1996 and to
      determine how costs differed between patients, diagnoses, and hospitals. PATIENTS
      AND METHODS: Patient characteristics and glaucoma-related resource use were
      collected for 500 patients with glaucoma or ocular hypertension from the medical
      records of 10 hospitals. Costs were calculated by multiplying the health care
      resource use of each patient with actual unit costs. Multiple least-squares
      regression was used to analyze the relationship between costs and patient
      characteristics, diagnosis, and type of hospital (general or academic). RESULTS:
      The mean annual frequency of visits to the ophthalmologist for patients with
      ocular hypertension and glaucoma was 2.43 and 3.74, respectively, and the mean
      cost per patient was $280 and $559, respectively. The mean cost of patients with
      glaucoma who had no changes in medication therapy was $347 and increased to
      $1,765 in patients with more than three adjustments in medication therapy.
      Outpatient visits to the ophthalmologist and medication contributed most to total
      costs. Regression analysis showed that costs were significantly related to
      intraocular pressure, diagnosis, severe excavation of the optic nerve head, and
      type of hospital. CONCLUSIONS: The costs of patients with glaucoma were twice as
      high as the costs of patients with ocular hypertension. Aside from diagnosis,
      differences in costs between patients could partly be explained by baseline
      patient characteristics. Patients in academic hospitals had more severe glaucoma
      and treatment was considerably more expensive than for patients in nonacademic
      hospitals.

PMID- 11442181
TI  - Correlation of visual field with quality-of-life measures at diagnosis in the
      Collaborative Initial Glaucoma Treatment Study (CIGTS).
AB  - PURPOSE: To examine the relationship between various clinical measures of visual
      field and patient-reported measures of symptoms and health status in a large
      cohort of patients with glaucoma at the time of diagnosis. PATIENTS AND METHODS:
      The 607 patients in the Collaborative Initial Glaucoma Treatment Study received
      standardized examinations of visual field at enrollment. In addition, they
      completed a telephone-administered, health-related quality-of-life questionnaire,
      which included the Visual Activities Questionnaire (VAQ) and a symptom and health
      problem checklist. RESULTS: The Visual Activities Questionnaire total and
      subscale scores, particularly the peripheral vision subscale, correlated weakly
      but significantly with global visual field scores. Symptoms attributed to
      glaucoma also correlated weakly but significantly to visual field scores.
      Correlations with other visual field measures, including only central and
      pericentral test locations in the scores, did not strengthen the association, and
      simulating binocular visual field scores produced only slightly stronger
      correlations. CONCLUSIONS: At diagnosis, most patients were relatively free of
      glaucoma-related impairments. Various visual field measures derived from clinical
      visual field test data were only modestly associated with patients' perceptions
      of health-related quality of life. As the Collaborative Initial Glaucoma
      Treatment Study population is followed up longitudinally, it will be important to
      see whether these pertinent associations become stronger.

PMID- 11442182
TI  - Can the specificity of the FDT for glaucoma be improved by confirming abnormal
      results?
AB  - PURPOSE: To determine whether the specificity of the frequency-doubling
      technology (FDT) perimeter in the screening mode for glaucoma can be improved by
      repeating abnormal screening results. METHODS: The FDT perimeter was used in C-20
      5 screening mode, and the right eye was tested first. After both eyes were
      tested, the screening was repeated in eyes with any abnormal visual field defects
      on FDT perimetry. The printouts were categorized as possible visual field
      abnormality (zero or one miss), probable visual field abnormality (two to four
      misses), and definite visual field abnormality (more than five misses). A
      clinical ophthalmologic examination was conducted on the day of the FDT perimetry
      screening. RESULTS: Complete data were available for 223 people. The participants
      ranged in age from 23 to 91 years (mean, 68.5 years; standard deviation. 13.7
      years), and 119 (53%) were women. The sensitivity of the FDT perimetry screening
      was 100%; both cases of glaucoma showed an abnormality on FDT perimetry both
      times. The specificity improved moderately from the first screening to the second
      screening. The specificity the first time was 62% (95% confidence interval, 53.1
      71.2). The specificity the second time was 68.5% (95% confidence interval, 59.8
      77.1). Improvement on FDT perimetry rescreening varied by the language spoken at
      home. Seven of the 19 non-English speakers without glaucoma improved on
      rescreening, compared with none of the 23 English speakers (P = 0.002). Seven of
      the 25 right eyes with FDT perimetry abnormalities both times and no glaucoma had
      no other detectable diseases. Three of 24 left eyes with FDT perimetry
      abnormalities both times and no glaucoma had no other detectable diseases. Of the
      85 patients who did not have glaucoma but had FDT perimetry abnormalities both
      times, only one did not have some other detectable disease. DISCUSSION: In
      summary, the sensitivity for glaucoma of the C-20-5 screening mode is excellent,
      but a paradigm for screening with the FDT perimeter to improve the overall
      specificity for glaucoma still must be developed.

PMID- 11442183
TI  - Overcoming the language barrier in visual field testing.
AB  - PURPOSE: To evaluate the effect of using recorded instructions in patients'
      native language compared with interpreter-assisted instructions on the
      reliability and duration of the visual field test. PATIENTS AND METHODS: Sixty
      patients referred for visual field testing were included in the study. Thirty
      five had limited or no knowledge of the Hebrew language, and 25 control patients
      were fluent in Hebrew, the native language. None had previous experience with
      automated perimetry. Patients were randomized to receive recorded instructions on
      the visual field test in their native language or translator-assisted
      instructions by the technician before performing the test. For each patient, the
      time required for instructions and test performance and the reliability indices
      were documented. RESULTS: The method of instruction (recorded or interpreter
      assisted) did not affect the time required for patient instructions (66 +/- 24
      seconds and 57 +/- 30 seconds, respectively), the time for test performance (7.2
      +/- 1.5 minutes and 7.8 +/- 1.8 minutes, respectively), and test reliability as
      measured by the rate of fixation losses. Regardless of the method of explanation,
      the time required for instructions and for performing the test were significantly
      shorter for Hebrew speakers than for non-Hebrew speakers. CONCLUSION: The use of
      a recorded explanation in the patient's native language before visual field
      testing is an applicable method for patient instruction. Clinics in areas with
      multilingual populations may use this method to save technicians time, without
      adversely affecting the time required for performing the test and its
      reliability.

PMID- 11442184
TI  - Central corneal thickness, tonometry, and ocular dimensions in glaucoma and
      ocular hypertension.
AB  - PURPOSE: To assess possible correlations between central corneal thickness,
      tonometry, and ocular dimensions. PATIENTS AND METHODS: One hundred seventeen
      eyes of 117 patients who were not taking any intraocular pressure-lowering
      medications were studied prospectively. Forty-one patients had ocular
      hypertension; 13 patients had primary open-angle glaucoma; and 10 patients had
      normal-pressure glaucoma. Twenty-three healthy eyes were included. Thirty
      glaucoma suspects (10 patients monitored for possible normal-pressure glaucoma
      and 20 patients with intermittent ocular hypertension) were included for
      correlation analysis. Tonometry was performed with Goldmann applanation and
      pneumotonometry, and central corneal thickness, anterior chamber depth, lens
      thickness, and axial length were measured ultrasonically. RESULTS: Central
      corneal thickness was lowest in eyes with normal-pressure glaucoma (538 +/- 51
      microm), highest in eyes with ocular hypertension (570 +/- 32 microm), and
      intermediate and similar in eyes with primary open-angle glaucoma and healthy
      eyes (547 +/- 34 microm and 554 +/- 32 microm, respectively). These differences
      were significant (P = 0.028). Goldmann applanation tonometry and central corneal
      thickness were weakly correlated (r = 0.12, P = 0.205), with a 0.2-mm Hg change
      per 10-microm variation in central corneal thickness. Pneumotonometry
      measurements were more strongly correlated with central corneal thickness (r =
      0.21, P < 0.05). Lens thickness was strongly correlated with age (r = 0.57, P <
      0.001). Anterior chamber depth was negatively correlated with lens thickness and
      age (r = -0.29, P < 0.005 and r = -0.25, P < 0.01). Axial length was correlated
      with anterior chamber depth and age (r = 0.5, P < .001 and r = -0.19, P < 0.05).
      CONCLUSION: Eyes diagnosed as having ocular hypertension have thicker corneas and
      eyes labeled as having normal-pressure glaucoma have thinner corneas, when
      compared with healthy eyes or eyes with primary open-angle glaucoma. The effect
      of central corneal thickness on Goldmann applanation tonometry accuracy appears
      to be small and usually not clinically relevant. When corneal thickness is
      markedly different from normal, the clinician may need to factor this into
      diagnosis and management.

PMID- 11442185
TI  - Topical verapamil in glaucoma filtration surgery.
AB  - PURPOSE: Because of the reported antifibroblastic effect of verapamil, a calcium
      channel blocker, we investigated the potential benefit of adjunctive topical
      verapamil in patients undergoing glaucoma filtration surgery. METHODS: This
      prospective, double-masked, randomized study included 56 eyes of 56 consecutive
      patients with chronic open-angle glaucoma undergoing trabeculectomy (primary or
      surgical revision of failed trabeculectomy), trabeculectomy combined with
      cataract surgery, or Molteno drainage device implantation. Postoperatively, the
      treated eyes received verapamil (0.25%) or one drop of placebo four times a day
      for 1 month in addition to 1% prednisolone four times a day and corticosteroid
      antibiotic ophthalmic ointment at bedtime. RESULTS: There were no significant
      differences in preoperative mean intraocular pressure, mean number of
      medications, and glaucoma severity between the verapamil and placebo groups.
      There were also no significant differences between the two groups in filtration
      success rate, mean intraocular pressure, and mean number of medications on
      postoperative days 1, 4, or 7 and at postoperative months 1, 2, 3, 4, 5, and 6 (P
      > 0.05). CONCLUSION: There was no significant benefit of adjunctive topical
      verapamil when it was used after trabeculectomy, trabeculectomy combined with
      cataract surgery, or Molteno drainage device implantation.

PMID- 11442186
TI  - Effect of pilocarpine 4% in combination with latanoprost 0.005% or 8-iso
      prostaglandin E2 0.1% on intraocular pressure in laser-induced glaucomatous
      monkey eyes.
AB  - PURPOSE: To compare the effect of pilocarpine, an agent that reduces uveoscleral
      outflow, on the ocular hypotensive efficacy of latanoprost and 8-iso
      prostaglandin E2 (PGE2). METHODS: Each of the two treatment groups was composed
      of the same eight monkeys with unilateral laser-induced glaucoma. Intraocular
      pressure (IOP) was measured hourly for 6 hours beginning at 9:00 AM on the
      baseline day (Thursday before treatment week) and on treatment days 1, 3, and 5
      (Monday, Wednesday, and Friday). On all five treatment days, one drop of
      pilocarpine 4% was administered at 9:00 AM and 3:00 PM and one drop of
      latanoprost 0.005% or 25 microL of 8-iso PGE2 0.1% was administered at 10:00 AM
      and 4:00 PM. RESULTS: One hour after pilocarpine instillation on day 1, the
      reduction of IOP was similar (P > 0.90) in both treatment groups, 7.6 +/- 1.1 mm
      Hg (mean +/- standard error of the mean ) in the latanoprost group and 7.4 +/-
      0.8 mm Hg in the 8-iso PGE2 group. However, the IOP effects of the two treatment
      groups became significantly different (P < 0.05) beginning 2 hours after dosing
      with latanoprost or 8-iso PGE, on day 1. A difference (P < 0.05) between the two
      groups persisted at all subsequent measurements. The reduction of IOP lessened
      with repeated dosing in the latanoprost and 8-iso PGE2 groups. Three hours after
      dosing with pilocarpine and two hours after dosing with the prostanoids, the IOP
      reduction was 8.3 +/- 0.9 mm Hg in the latanoprost group and 9.9 +/- 0.6 mm Hg in
      the 8-iso PGE2 group on day 1, and 2.1 +/- 1.0 mm Hg in the latanoprost group and
      7.3 +/- 0.9 mm Hg in the 8-iso PGE1 group on day 5. CONCLUSIONS: The smaller
      reductions in IOP with pilocarpine and latanoprost than with pilocarpine and 8
      iso PGE2 show that pilocarpine blocks much more of the ocular hypotensive effect
      of latanoprost than of 8-iso PGE2. The results also indicate that pilocarpine and
      latanoprost are mutually antagonistic. Enhancement of uveoscleral outflow appears
      to account for most of the ocular hypotensive effect of latanoprost and for much
      less of the ocular hypotensive effect of 8-iso prostaglandin E2.

PMID- 11442187
TI  - Effectiveness and safety of brimonidine as adjunctive therapy for patients with
      elevated intraocular pressure in a large, open-label community trial.
AB  - PURPOSE: To determine the effectiveness and safety of brimonidine when used in
      combination with one or more glaucoma medications in patients with glaucoma or
      ocular hypertension. METHODS: Post hoc analysis of a multicenter, 2-month, open
      label, prospective, clinical trial in which 2,335 patients received brimonidine
      as monotherapy, replacement therapy, or combination therapy. Patients who
      received brimonidine as combination therapy (n = 554) were examined in the
      current analysis. Efficacy was determined by the reduction in intraocular
      pressure (IOP) from baseline before the addition of brimonidine. Safety and
      tolerability parameters included adverse events and quality-of-life measures
      (e.g., ocular comfort, energy level, breathing ability, night vision). RESULTS:
      Addition of brimonidine to preexisting regimens resulted in an overall mean
      additional reduction in IOP of 17.9% (4.26 mm Hg) at month 2 (P < 0.001).
      Significant additional IOP lowering was provided by brimonidine in combination
      with each preexisting regimen evaluated (P < or = 0.061). When brimonidine was
      added to monotherapy with a nonselective beta-blocker, the mean additional IOP
      reduction was 15.5% (3.61 mm Hg, P < 0.001). Addition of brimonidine to
      latanoprost monotherapy provided a 32.2% (5.89 mm Hg) mean additional IOP
      reduction (P < 0.001). Addition of brimonidine to combination regimens that
      included latanoprost provided additional mean decreases in LOP ranging from 15.5%
      (3.63 mm Hg, P < 0.002) to 20.1% (6.62 mm Hg, P < 0.001). All quality-of-life
      parameters remained high or improved during the study. Mild to moderate adverse
      events were reported in 5.23% of patients (29 of 552); 98.1% of physicians rated
      brimonidine adjunctive therapy as good or excellent. CONCLUSIONS: Brimonidine,
      when added to existing glaucoma regimens, safely and effectively lowered IOP in
      this community-based trial.

PMID- 11442188
TI  - Effect of timolol 0.5% gel and solution on pulmonary function in older glaucoma
      patients.
AB  - PURPOSE: To evaluate the effect of timolol maleate solution or gel forming
      solution versus placebo on pulmonary function in patients with primary open-angle
      glaucoma or ocular hypertension without reactive airway disease. METHODS: After a
      screening visit, each patient was randomized by a Latin square technique to
      receive placebo twice daily, 0.5% timolol solution twice daily, or 0.5% timolol
      gel once a day (placebo given as second dose) to each eye for 2 weeks. Subjects
      then were crossed over to the two other treatments for 2-week treatment
      intervals. At each visit, patients were received a dose 15 minutes before
      pulmonary function testing. RESULTS: This study began with 25 patients, and 20
      finished the trial. There was no difference between treatment groups for the
      forced expiratory volume at one second (FEV1), forced vital capacity (FVC),
      FEV1/FVC ratio (P > 0.1). The mean FEV1 for timolol solution, timolol gel, and
      placebo was 2.42 L, 2.45 L, and 2.50 L, respectively. The mean FVC for timolol
      solution, timolol gel, and placebo was 3.33 L, 3.38 L, and 3.44 L, respectively.
      No difference in intraocular pressure was observed between the timolol solution
      (17.1 +/- 3.3 mm Hg) and timolol gel (17.1 +/- 3.6 mm Hg) between the treatment
      periods (P > 0.1). No difference in side effects was observed between treatment
      groups (P > 0.05). CONCLUSIONS: In older patients with primary open-angle
      glaucoma or ocular hypertension without reactive airway disease, nonselective
      beta-blockers should not worsen pulmonary function.

PMID- 11442189
TI  - Cystoid macular edema associated with topical latanoprost in glaucomatous eyes
      with a normally functioning blood-ocular barrier.
AB  - PURPOSE: To study prospectively using optical coherence tomography (OCT) whether
      topical latanoprost induces retinal disorders, such as cystoid macular edema, in
      patients with glaucoma and a normally functioning blood-ocular barrier. METHODS:
      Sixty-eight eyes of 38 patients with glaucoma and no history of intraocular
      surgery, uveitis, or laser trabeculoplasty were studied. Before initiation of
      latanoprost treatment and after 1, 3, and 6 months of treatment, OCT images were
      taken, and the following tests were performed: visual acuity examination, fundus
      ophthalmoscopy, intraocular pressure measurement, and fundus color photography.
      To evaluate retinal thickness in the fovea accurately. OCT scanning was repeated
      six times, and the smallest value was used as the retinal thickness in the fovea.
      RESULTS: Latanoprost ophthalmic solution did not influence retinal thickness in
      the fovea at any investigated time points compared with the time before
      instillation, and no changes were observed in visual acuity, ophthalmoscopic
      findings, and fundus photographs. The intraocular pressure was reduced
      significantly at all investigated time points compared with the time before
      instillation. CONCLUSIONS: It is unlikely that topical latanoprost induces
      retinal disorders, such as cystoid macular edema, in glaucomatous eyes with a
      normally functioning blood-ocular barrier.

PMID- 11442190
TI  - Trabeculectomy, risk factors for failure and the preoperative state of the
      conjunctiva.

PMID- 11442191
TI  - Autologous platelet concentrate injection into overfiltrating or leaking
      filtering blebs.

PMID- 11442192
TI  - Interspecific interactions between larval digeneans in the eyes of perch, Perca
      fluviatilis.
AB  - The changes in prevalence and abundance of the three species of metacercariae in
      the humour of the eyes of perch Perca fluviatilis in Slapton Ley, Devon, have
      been monitored over a period of 29 years. Earlier studies had revealed that
      Diplostomum gasterostei was originally the sole occupant of this niche, but
      Tylodelphys clavata colonised in 1973 and T. podicipina in 1976. A decline in the
      number of perch with heavy infections of D. gasterostei was significantly
      negatively correlated with population abundance of T. clavata and a decline in
      recruitment rate of D. gasterostei coincided with the population increase in T.
      podicipino over the period 1976-1979. It was suggested that the decline in
      population size of D. gasterostei was due to inter-specific competition, but this
      hypothesis could not be tested experimentally. Subsequent investigations,
      reported here, confirmed the decline when the data set was extended to 1985. A
      severe decline in the perch population over the winter of 1984/1985 resulted in
      the disappearance of D. gasterostei and T. podicipina and this was followed by a
      slow recovery from 1990 onwards. This natural experiment provided an opportunity
      to test the hypothesis. Only T. clavata survived throughout the perch crash and
      the population continued at pre-crash levels up to 1999. Its congener T.
      podicipina did not re-appear until 1994 and was probably a re-introduction: it
      did not attain pre-crash levels until 1999. It is likely that D. gasterostei
      survived the crash as it re-appeared in 1991, but was confined to young of the
      year fish and barely approached pre-crash levels even in 1999. Its continual low
      levels cannot be explained by changes in the lake or in densities of snail
      intermediate or bird definitive hosts. New data revealed that the suspensory
      ligaments of the eye were the preferred site of all three species and that the
      eye was partitioned out between them. The data from the post-crash period do not
      refute but rather confirm earlier conclusions that inter-specific competition is
      responsible for the decline in D. gasterostei and this remains the preferred
      hypothesis.

PMID- 11442193
TI  - Concomitant infections, parasites and immune responses.
AB  - Concomitant infections are common in nature and often involve parasites. A number
      of examples of the interactions between protozoa and viruses, protozoa and
      bacteria, protozoa and other protozoa, protozoa and helminths, helminths and
      viruses, helminths and bacteria, and helminths and other helminths are described.
      In mixed infections the burden of one or both the infectious agents may be
      increased, one or both may be suppressed or one may be increased and the other
      suppressed. It is now possible to explain many of these interactions in terms of
      the effects parasites have on the immune system, particularly parasite-induced
      immunodepression, and the effects of cytokines controlling polarization to the
      Th1 or Th2 arms of the immune response. In addition, parasites may be affected,
      directly or indirectly, by cytokines and other immune effector molecules and
      parasites may themselves produce factors that affect the cells of the immune
      system. Parasites are, therefore, affected when they themselves, or other
      organisms, interact with the immune response and, in particular, the cytokine
      network. The importance of such interactions is discussed in relation to clinical
      disease and the development and use of vaccines.

PMID- 11442194
TI  - Interactions between species and the structure of helminth communities.
AB  - The role of interspecific interactions in the structure of gastrointestinal
      helminth communities has been at the core of most research in parasite community
      ecology, yet there is no consensus regarding their general importance. There have
      been two different approaches to the study of species interactions in helminths.
      The first one consists of measuring the responses of helminth species in
      concomitant infections, preferably in laboratory experiments. Any change in
      numbers of parasite individuals or in their use of niche space, compared with
      what is observed in single infections, provides solid evidence that the species
      are interacting. The second approach can only provide indirect, circumstantial
      evidence. It consists in contrasting observed patterns either in the distribution
      of species richness of infracommunities from wild hosts, in their species
      composition, or in pairwise associations between helminth species among
      infracommunities, with the random patterns predicted by appropriate null models.
      In many cases, observed patterns do not depart from predicted ones; when they do,
      alternative explanations are usually as plausible as invoking the effect of
      interactions among helminth species. The present evidence suggests that the role
      of species interactions in helminth community structure is often negligible, but
      that it must always be evaluated on a case-by-case basis.

PMID- 11442195
TI  - Interactions involving intestinal nematodes of rodents: experimental and field
      studies.
AB  - Multiple species infections with parasitic helminths, including nematodes, are
      common in wild rodent populations. In this paper we first define different types
      of associations and review experimental evidence for different categories of
      interactions. We conclude that whilst laboratory experiments have demonstrated
      unequivocally that both synergistic and antagonistic interactions involving
      nematodes exist, field work utilizing wild rodents has generally led to the
      conclusion that interactions between nematode species play no, or at most a
      minor, role in shaping helminth component communities. Nevertheless, we emphasize
      that analysis of interactions between parasites in laboratory systems has been
      fruitful, has made a fundamental contribution to our understanding of the
      mechanisms underlying host-protective intestinal immune responses, and has
      provided a rationale for studies on polyparasitism in human beings and domestic
      animals. Finally, we consider the practical implications for transmission of
      zoonotic diseases to human communities and to their domestic animals, and we
      identify the questions that merit research priority.

PMID- 11442196
TI  - Heterologous immunity revisited.
AB  - Heterologous immunity, or protection by one invading organism against another
      across phylogenetic divides, has been recognised for decades. It was initially
      thought to operate largely through enhancement of phagocytosis, but this
      explanation became untenable when it was realised it worked extremely well
      against intraerythrocytic protozoa and killed them while they were free in the
      circulation. Clearly a soluble mediator was called for. This review summarises
      the logic that arose from this observation, which led to a wider appreciation of
      the roles of pro-inflammatory cytokines, and then nitric oxide, in the host's
      response against invaders, as well as the ability of these mediators to harm the
      host itself if they are generated too enthusiastically. This has led to a
      discernable pattern across heterologous immunity as a whole, and its lessons
      influence a range of areas, including vaccine development.

PMID- 11442197
TI  - Use of an optimality model to solve the immunological puzzle of concomitant
      infection.
AB  - Immunological data indicate that different subsets of T-helper cells work best
      against different types of infection. Concomitant infection of a host may thus
      impose either conflicting or synergistic immune response requirements, depending
      upon the extent to which the component optimal immune responses differ. Drawing
      upon empirically-determined optimal responses to single-species infections, an
      optimality model is here used to generate testable hypotheses for optimal
      responses to concomitant infection. The model is based upon the principle that
      the joint immune response will minimize divergence from each of the optima for
      single-species infections, but that it will also be weighted by the importance of
      mounting the correct response against each infectious organism. The model thus
      predicts a weighted average response as the optimal response to concomitant
      infection. Data on concomitant infection of murine hosts by the parasites
      Schistosoma mansoni and Toxoplasma gondii will provide the first test of the
      optimality model. If the weighted average hypothesis holds true, then there are
      no emergent immunological properties of concomitant infections and we may be able
      to understand immune responses to concomitant infection directly via our
      understanding of single-species infections.

PMID- 11442198
TI  - Parasitic diseases and immunodeficiencies.
AB  - In the last two decades, major immunodeficiency syndromes have strongly
      influenced medical parasitology. Some animal parasitoses, once unknown in human
      medicine, have become zoonotic and sometimes anthroponotic. In other cases, the
      clinical evolution of human parasitoses has been severely aggravated and/or
      modified in immunodeficient patients especially in toxoplasmosis,
      cryptosporidiosis, leishmaniasis, strongyloidiasis and scabies. The parasites
      implicated are varied (protozoa, helminths and even Acaridae) but have in common
      the capacity to reproduce in or on the human host. These immunodeficiency
      syndromes are often related to AIDS but other major immunodepressions, such as
      post-therapeutically in organ transplantation, may also be responsible and raise
      difficult problems for prevention. The munological mechanisms involved are not
      always well understood. In addition, genetic predisposition factors, gradually
      becoming better-understood in parasites and man, complete and complicate our
      understanding of the immunological mechanisms.

PMID- 11442199
TI  - Multiple helminth infections in children: impact and control.
AB  - Parasitic worm infections are amongst the most widespread of all chronic human
      infections. It is estimated that there are more than 3 billion infections in the
      world today. In many low income countries it is often more common to be infected
      than not to be. Indeed, a child growing up in an endemic community can expect be
      infected soon after weaning, and to be infected and constantly reinfected for the
      rest of her or his life. Infection is most common amongst the poorest and most
      disadvantaged communities, and is typically most intense in children of school
      going age. As the risk of morbidity is directly related to intensity of
      infection, it follows that children are the most at risk from the morbid effects
      of disease. Multiparasite infections are also common in such communities and
      there is evidence that individuals harbouring such infections may suffer
      exacerbated morbidity, making children even more vulnerable. Thus, these
      infections pose a serious threat to the health and development of children in low
      income countries. For many years, the need to control these infections has lain
      uncontested, and with the advent of broad-spectrum anthelminthic drugs that are
      cheap, safe and simple to deliver, control has at last become a viable option for
      many communities. Furthermore, there is now increased emphasis being placed on a
      multispecies approach as a cost-effective mechanism to control the morbidity of
      virtually all the major helminthic infections of humans.

PMID- 11442200
TI  - Chemotherapy for patients with multiple parasitic infections.
AB  - Multiple parasitic infections have become increasingly recognized as a result of
      improvements in laboratory diagnosis and a growing population of
      immunocompromised individuals. This review examines the principles of
      chemotherapy in groupings of multiple infections which are of particular clinical
      significance.

PMID- 11442201
TI  - Immunoisolation cell therapy for CNS diseases.
AB  - Delivery of potentially therapeutic drugs to the brain is hindered by the blood
      brain barrier (BBB), which restricts the diffusion of drugs from the vasculature
      to the brain parenchyma. One means of overcoming the BBB is with cellular
      implants that produce and deliver therapeutic molecules directly into the CNS
      region of interest. In this paper we describe the current status of one iteration
      of cell-based therapy that uses xenogeneic cells encased within a selectively
      permeable polymeric membrane; this is known as immunoisolation. For the purposes
      of this review, cell immunoisolation for treating CNS diseases is presented in
      terms of device configurations, membrane manufacturing, characterization in
      relevant preclinical model systems, and the current status of clinical trials.

PMID- 11442202
TI  - Antibody-Based targeting of angiogenesis.
AB  - Angiogenesis-the sprouting of new blood vessels from pre-existing ones-is a
      characteristic feature of relevant diseases such as cancer, some blinding ocular
      disorders, rheumatoid arthritis, and psoriasis. This article reviews recent
      progress in the generation of monoclonal antibodies, which recognize and target
      new blood vessels in vivo, while sparing mature vessels and healthy tissues. The
      use of such antibodies as selective "molecular vehicles" is likely to open new
      important diagnostic and therapeutic opportunities.

PMID- 11442203
TI  - Plasmodium coatneyi: observations on periodicity, mosquito infection, and
      transmission to Macaca mulatta monkeys.
AB  - Plasmodium coatneyi has adapted well to experimental studies with Macaca mulatta
      monkeys and Anopheles dirus mosquitoes. Studies were made to determine 1) the
      course of asexual parasitemia, 2) periods when infective gametocytes were
      produced, 3) the laboratory-reared mosquitoes susceptible to infection, 4) the
      mosquito most capable of transmitting the infection to monkeys via bite, 5) the
      pattern of recrudescence, and 6) the prepatent periods following the bites of
      infected An. dirus mosquitoes. The period when infective gametocytes are produced
      is concentrated primarily in the first week when parasitemia exceeds
      1,000/microl. Mosquitoes were more heavily infected on days when the asexual
      parasite counts were highest. Gametocyte counts were generally low. Mature forms
      of the parasite markedly sequestered giving a pattern of high-low periodicity.
      Anopheles dirus and An. freeborni mosquitoes were nearly equal in terms of their
      ability to support oocyst development. Other species (An. stephensi, An.
      maculatus, and An. gambiae.) were less supportive. High sporozoite densities in
      the salivary glands were frequently produced in An. dirus and sporozoite
      transmission was obtained via the bites of these mosquitoes after 12-18 days of
      extrinsic incubation. Prepatent periods ranged from 10 to 15 days. The presence
      of frequent parasitic recrudescences suggests mechanisms similar to that seen in
      human infections with P. falciparum. It is proposed that P. coatneyi in M.
      mulatta monkeys can be a suitable model for studies on cerebral pathology,
      vaccine efficacy, and the testing of antimalarial drugs.

PMID- 11442204
TI  - Pirital virus (Arenaviridae) infection in the syrian golden hamster, Mesocricetus
      auratus: a new animal model for arenaviral hemorrhagic fever.
AB  - Adult Syrian golden hamsters inoculated intraperitoneally with Pirital virus, a
      recently discovered member of the Tacaribe complex of New World arenaviruses,
      developed a progressively severe, fatal illness with many of the pathologic
      features observed in fatal human cases of Lassa fever and other arenaviral
      hemorrhagic fevers. Most of the animals became moribund by Day 5 and were dead by
      Day 7 after inoculation. The most consistent histopathologic changes included
      interstitial pneumonitis, splenic lymphoid depletion and necrosis, and multifocal
      hepatic necrosis without significant inflammatory cell infiltration. The liver
      changes ranged from single cell death by apoptosis to coagulative necrosis of
      clusters of hepatocytes. Immunohistochemical studies of the liver demonstrated
      the presence and accumulation ot Pirital virus antigen within hepatocytes as well
      as Kupffer cells. An in situ terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling (TUNEL) assay showed progressively increasing apoptotic
      activity in the liver of infected hamsters. A human hepatoblastoma cell line (Hep
      G2/C3A) inoculated with Pirital virus also developed progressive cell destruction
      and accumulation of viral antigen, as demonstrated by immunofluorescence. Results
      of this pilot study suggest that the Pirital virus-hamster model is a very
      promising new small animal model for studying the pathogenesis of arenavirus
      infections, particularly, the mechanism of direct virus-induced hepatic injury.
      It may also be useful for testingantiviral agents for treatment of arenaviral
      hemorrhagic fevers.

PMID- 11442205
TI  - Canine visceral leishmaniasis in Colombia: relationship between clinical and
      parasitologic status and infectivity for sand flies.
AB  - We studied the reservoir competency of canines with distinct clinical
      presentations of Leishmania chagasi infection. The parasitologic status of
      asymptomatic and symptomatic dogs was determined by standard culture methods
      Infectivity was assessed by multiple xenodiagnoses with Lutzomyia longipalpis,
      over a period of 2-11 months. Asymptomatic dogs were non-infective (0 of 5) while
      2 of 7 oligosymptomatic dogs infected L longipalpis, transmitting the parasites
      at low rates (range 0.9-5.2% of engorged flies). Polysymptomatic dogs transmitted
      L. chagasi more frequently (4 of 8 dogs) and reached higher infection rates
      (range 5.0-22.5% of engorged flies). The skin of the ear tended to be more
      infective to sand flies than that of the abdomen. Polymerase chain reaction
      hybridization (PCR-H) was a sensitive method for detection of L. chagasi,
      yielding the highest positive rate in serum (16 of 17 dogs) with no distinction
      between clinical groups. No association between skin positivity by PCR-H and
      infectivity to sand flies was found. The infectivity of dogs from clinically
      comparable groups from Colombian and Mediterranean foci differed. This may be a
      reflection of varied nutritional conditions or vector competency of distinct sand
      fly species.

PMID- 11442206
TI  - Flaviviruses isolated from mosquitoes collected during the first recorded
      outbreak of Japanese encephalitis virus on Cape York Peninsula, Australia.
AB  - In response to an outbreak of Japanese encephalitis (JE) virus on Cape York
      Peninsula, Australia, in 1998, mosquitoes were collected using CO2 and octenol
      baited Centers for Disease Control and Prevention light traps. A total of 35,235
      adult mosquitoes, comprising 31 species, were processed for virus isolation. No
      isolates of JE virus were recovered from these mosquitoes. However, 18 isolates
      of Kokobera virus, another flavivirus were obtained from Culex annulirostris.
      Twelve isolates were from western Cape York (minimum infection rate (MIR) of
      0.61: 1,000 mosquitoes) and 6 were from the Northern Peninsula Area (MIR of
      1.0:1,000). Potential explanations for the failure to detect JE virus in
      mosquitoes collected from Cape York Peninsula include the timing of collections,
      the presence of alternative bloodmeal hosts, differences in pig husbandry,
      asynchronous porcine seroconversion, and the presence of other flaviviruses.

PMID- 11442207
TI  - Effect of climatic factors and population density on varicella zoster virus
      epidemiology within a tropical country.
AB  - Blood samples were collected from healthy subjects, aged 9 months-29 years in
      urban and rural communities from 4 distinct regions in Thailand, to determine the
      seroprevalence rate of varicella-zoster virus (VZV) antibody and its relationship
      with demographic, climatic, and socioeconomic factors. The overall seroprevalence
      rate was 52.8% and increased from 15.5% in the 9-month to 4-year-old group to
      75.9% in the 20-29 year-olds. The age-adjusted seroprevalence was significantly
      higher in the cooler than in the warmer regions. In the warmer regions only, the
      age-specific seroprevalence was significantly higher in the urban population than
      in the rural population. In Thailand, climate is the main determinant of VZV
      seroprevalence. The delayed onset of natural immunity is more marked in warmer
      climate areas. Population density is a secondary determinant; in the warmer
      areas, the pattern of adolescent and adult susceptibility was greater in rural
      than in urban areas.

PMID- 11442208
TI  - Antibody to sin nombre virus in rodents associated with peridomestic habitats in
      west central Montana.
AB  - Most human cases of hantavirus pulmonary syndrome are acquired in the
      peridomestic environment, yet studies of the ecology and infection dynamics in
      the reservoir host, the deer mouse (Peromyscus maniculatus), have focused on
      sylvan populations. We describe a 2.5-year study of hantavirus infection in
      rodents associated with peridomestic habitats in west central Montana. Antibodies
      reactive with Sin Nombre virus (SNV) were found in five species. Overall SNV
      antibody prevalence was highest among deer mice (25% of individuals tested). As
      has been demonstrated for sylvan populations, the antibody-positive component of
      the deer mouse population consisted of a higher proportion of adults and males.
      However, the prevalence of antibodies to SNV was higher in this study than has
      been reported in most sylvan studies. The average monthly proportion of deer
      mouse blood samples with antibodies to SNV ranged from approximately 20% to 25%
      and was highest in the late spring/early summer. The higher SNV antibody
      prevalence in peridomestic compared with sylvan settings may be related to
      behavioral differences and/or potentially longer survival of the virus deposited
      inside buildings. Peridomestic settings presented higher concentrations of virus
      and may present a higher risk of human infection than do sylvan settings.

PMID- 11442209
TI  - Hepatitis c and cirrhotic liver disease in the Nile delta of Egypt: a community
      based study.
AB  - Residents of Egypt's Nile river delta have among the world's highest
      seroprevalence of hepatitis C virus (HCV) infection. To assess the impact of HCV
      on chronic liver disease, we studied the association between HCV, other hepatitis
      viruses, and cirrhotic liver disease in a cross-sectional, community-based survey
      of 801 persons aged > or = 10 years living in a semi-urban, Nile delta village.
      Residents were systematically sampled using questionnaires, physical examination,
      abdominal ultrasonography and serologically for antibodies to HCV (confirmed by a
      third-generation immunoblot assay) and to hepatitis A virus (HAV), hepatitis B
      virus (HBV), and hepatitis E virus (HEV). The seroprevalence of HCV increased
      with age from 19% in persons 10-19 years old to about 60% in persons 30 years and
      older. Although no practices that might facilitate HCV transmission were
      discovered, the seroprevalence of HCV was significantly associated with remote (>
      1 year) histories of schistosomiasis. Sonographic evidence of cirrhosis was
      present in 3% (95% CI: 1%, 4%) of the population (0.7% of persons under 30 years
      of age and in 5% of older persons), and was significantly associated with HCV
      seroreactivity. Our findings are consistent with the hypothesis that past mass
      parenteral chemotherapy campaigns for schistosomiasis facilitated HCV
      transmission, and that HCV may be a major cause of the high prevalence of liver
      cirrhosis in this Nile village.

PMID- 11442210
TI  - The increasing burden of infectious diseases on hospital services at St Mary's
      Hospital Lacor, Gulu, Uganda.
AB  - To evaluate the impact of infectious diseases on hospital services in Northern
      Uganda, a retrospective analysis of discharge records concerning 70,304
      inpatients admitted to the Lacor Hospital (Gulu, Uganda) during the period 1992
      1997 was performed. Children less than five years old represented 46.5% of the
      admissions, and the burden of infectious diseases on pediatric admissions
      increased over time, especially due to malaria and measles. Infectious diseases
      accounted for 7 of the 10 leading causes of admission. The most frequent cause
      was malaria (21.8% of total). The second leading infectious disease resulting in
      admission was respiratory tuberculosis (6.2%); given the long hospital stay, this
      is the most important disease in terms of hospital bed days (24.6%). Infectious
      diseases have represented a progressively heavy burden on hospital services,
      mostly due to pediatric admissions. Respiratory tuberculosis and malaria
      represent nearly one-third of the overall burden in terms of hospital bed days.

PMID- 11442211
TI  - Case report: recovery of Calliphora vicina first-instar larvae from a human
      traumatic wound associated with a progressive necrotizing bacterial infection.
AB  - Human myiasis caused by Calliphora vicina is rare in Europe. Here we report a
      case of C. vicina infection occurring in the traumatic leg wound of a healthy 21
      year-old man. Firstly, a progressive necrotizing infection developed in the wound
      despite administration of antibiotics. Aeromonas hydrophila was isolated from the
      wound samples. Secondly, during debridement, C. vicina first-instar larvae were
      isolated from the wound. To our knowledge, this is the first European case of C.
      vicina wound myiasis associated with severe A. hydrophila infection.

PMID- 11442212
TI  - Four cases of acute chagasic myocarditis in French Guiana.
AB  - The authors report four cases of acute chagasic myocarditis which had been
      diagnosed and treated in Cayenne, French Guiana, in the past 6 years. This French
      territory, which has the highest standard of living in South America, should be
      considered an area of risk for sporadic Chagas disease with epidemiologic
      features similar to those of the disease found in dense Amazon forest areas.
      Appropriate measures must be taken to screen and promptly manage Chagas disease
      in the French Guiana population.

PMID- 11442213
TI  - Randomized intervention study comparing several regimens for the treatment of
      moderate anemia among refugee children in Kigoma Region, Tanzania.
AB  - Anemia-specific mortality was markedly elevated among refugee children < 5 years
      of age in Tanzania. In a randomized, double-blind study, 215 anemic children were
      initially treated for malaria and helminth infection and then received 12 weeks
      of thrice-weekly oral iron and folic acid. Group I received placebo and
      chloroquine treatment for symptomatic malaria infection (i.e., no presumptive
      anti-malarial treatment given). Group II received placebo and monthly presumptive
      treatment with sulfamethoxazole-pyrimethamine (SP). Group III also received
      monthly SP and thrice-weekly vitamins A and C (VAC). Mean hemoglobin
      concentration increased from 6.6 to 10.2 g/dL, with no significant differences
      among groups. Group II had lower mean serum transferrin receptor levels (TfR)
      than group I [P = 0.023]. A greater proportion of participants in group III had
      normal iron stores (TfR < 8.5 microg/ mL) than in group II [P = 0.012]. Initial
      helminth and malaria treatment, followed by thrice-weekly iron and folic acid
      supplements resulted in increased hemoglobin levels. Monthly SP and thrice-weekly
      VAC contributed to improve iron stores. Monthly SP may have a role in situations
      where asymptomatic disease is prevalent or where access to care is limited.
      Because administration of VAC also hastened recovery of iron stores over
      administration of monthly SP alone, health care personnel could add VAC to the
      treatment for moderate anemia if maximum recovery of iron stores is desired.

PMID- 11442214
TI  - Community-acquired pneumonia in Ugandan adults: short-term parenteral ampicillin
      therapy for bacterial pneumonia.
AB  - A hospital-based prospective study of 99 patients with community-acquired
      pneumonia (CAP) was carried out in Kampala, Uganda. We evaluated microbiological
      etiologies, clinical features and effectiveness of short-term parenteral
      ampicillin followed by oral amoxicillin for these patients in relation to HIV
      status. We demonstrated a very high prevalence (75%) of HIV-1 infection. No
      significant difference was observed with respect to age, gender, prior antibiotic
      usage, symptoms, laboratory data or bacterial etiology between HIV-1-infected and
      HIV-uninfected CAP patients. Most strains of Streptococcus pneumoniae (n = 19)
      and Haemophilus influenzae (n = 8) isolated from HIV-1-infected patients were
      penicillin-resistant (95%) and beta-lactamase producing (75%) strains,
      respectively. A high percentage of good clinical response was found in both HIV-1
      infected (81%) and HIV-uninfected (86%) among 39 patients with CAP due to a
      defined bacterial pathogen. These data support the use of short-term parenteral
      ampicillin for patients with bacterial CAP irrespective of HIV-status.

PMID- 11442215
TI  - Cost-effectiveness of sulfadoxine-pyrimethamine for the prevention of malaria
      associated low birth weight.
AB  - Prevention of placental malaria through administration of antimalarial
      medications to pregnant women in disease-endemic areas decreases the risk of
      delivery of low birth weight (LBW) infants. In areas of high Plasmodium
      falciparum transmission, two intermittent presumptive treatment doses of
      sulfadoxine-pyrimethamine (SP) during the second and third trimesters of
      pregnancy are effective in decreasing the prevalence of placental malaria in
      human immunodeficiency virus (HlV)-negative women, while HIV-positive women may
      require a monthly SP regimen to reduce their prevalence of placental parasitemia.
      A decision-analysis model was used to compare the cost-effectiveness of three
      different presumptive SP treatment regimens with febrile case management with SP
      in terms of incremental cost per case LBW prevented. Factors considered included
      HIV seroprevalence, placental malaria prevalence, LBW incidence, the cost of SP,
      medical care for LBW infants, and HIV testing. For a hypothetical cohort of
      10,000 pregnant women, the monthly SP regimen would always be the most effective
      strategy for reducing LBW associated with malaria. The two-dose SP and monthly SP
      regimens would prevent 172 and 229 cases of LBW, respectively, compared with the
      case management approach. At HIV seroprevalence rates greater than 10%, the
      monthly SP regimen is the least expensive strategy. At HIV seroprevalence rates
      less than 10%, the two-dose SP regimen would be the less expensive option. When
      only antenatal clinic costs are considered, the two-dose and monthly SP
      strategies cost US $11 and $14, respectively, well within the range considered
      cost effective. Presumptive treatment regimens to prevent LBW associated with
      malaria and the subsequent increased risk of mortality during the first year of
      life are effective and cost effective strategies in areas with both elevated HIV
      prevalence and malaria transmission rates.

PMID- 11442216
TI  - Treatment failure in children in a randomized clinical trial with 10 and 20 days
      of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia
      species.
AB  - Clinical response to supervised treatment of Colombian patients with cutaneous
      leishmaniasis was evaluated in a randomized controlled trial comparing 10 days
      versus 20 days of treatment with meglumine antimonate (20 mg Sb/kg/day). Masked
      examiners evaluated clinical response defined as 100% re-epithelialization of all
      lesions at 13 weeks and no relapses during 52 weeks of follow-up. The efficacy of
      meglumine antimonate for 10 days' treatment was 61% (28 of 46) compared to 67%
      (24 of 36) for 20 days. There was a significantly lower clinical response for
      children < 5 years in both 10-day (11%) and 20-day (25%) groups compared to
      patients aged 5-14 years (67% and 75%, respectively) and 15 years or more (81%
      and 83%, respectively). Overall efficacy of treatment schedules was comparable,
      but lower than expected, mainly because of low efficacy in children.
      Pathogenicity of infection and pharmacokinetics may affect the treatment response
      in children. New therapeutic alternatives should be evaluated in trials that
      include children and women.

PMID- 11442217
TI  - Identification of frequently recognized dimorphic T-cell epitopes in plasmodium
      falciparum merozoite surface protein-1 in West and East Africans: lack of
      correlation of immune recognition and allelic prevalence.
AB  - The merozoite surface protein-1 (MSP1) is the most studied malaria blood-stage
      vaccine candidate. Lymphokines such as interferon gamma (IFN-gamma) and
      interleukin 4 (IL-4) may mediate blood-stage specific protection. Here we
      identify Plasmodiumfalciparum MSP1 T-cell epitopes capable of rapid induction of
      IFN-gamma and/or IL-4 from peripheral blood mononuclear cells of East and West
      African donors. Both allelic forms of these novel MSP1 T-cell epitopes were
      stimulatory. An unusually high numbers of Gambian responders (> 80%) to these
      epitopes were observed, suggesting that MSPI reactivity may have been
      underestimated previously in this population. Surprisingly, IFN-gamma responses
      to allelic T-cell epitopes failed to correlate with differential antigenic
      exposure in The Gambia compared to Kenya. These results suggest an unexpected
      level of immunoregulation of IFN-gamma response with variable allelic T-cell
      reactivity independent of the level of antigenic exposure. Further analysis of
      the mechanisms determining this response pattern may be required if vaccines are
      to overcome this allelic reactivity bias in malaria-exposed populations.

PMID- 11442218
TI  - Short report: IgG1/IgG3 antibody responses to various analogs of recombinant
      ypfmsp119--a study in immune adults living in areas of Plasmodium falciparum
      transmission.
AB  - To further characterize protective-type (IgG1/IgG3) antibody responses to
      Plasmodium falciparum blood stage in putatively immune individuals' plasma, we
      have tested for various analogs of the 19 kDa C-terminus of the MSP1 antigen
      obtained as secreted recombinant proteins from Saccharomyces cerevisiae. One of
      four proteins was then identified on the basis of consistent IgG3, along with
      less variable IgG1 recognition. This protein has thus been selected for further
      functional assays of IgG1/IgG3 antibodies.

PMID- 11442219
TI  - Blood-brain barrier function in cerebral malaria in Malawian children.
AB  - Cerebral malaria (CM) is a serious complication of Plasmodium falciparum
      infection. Binding of parasitized erythrocytes to cerebral endothelium plays a
      key role in disease pathogenesis. Central nervous system signs and symptoms
      (coma, seizures, raised intracranial pressure) predominate in African children,
      whereas in adults, multiorgan system failure is more common. In this study we
      investigated whether changes in blood-brain barrier (BBB) structure and function
      are compatible with the signs and symptoms observed in Malawian children with CM.
      Immunohistochemistry on autopsy brain tissues from eight cases of CM showed
      activation of endothelial cells and macrophages, and disruption of endothelial
      intercellular junctions in vessels containing sequestered parasitized
      erythrocytes, but no gross leakage of plasma proteins. Examination of the
      partition of albumin between circulating plasma and the cerebrospinal fluid from
      72 cases of CM showed subtle but measurable changes compatible with impaired BBB
      function in malaria. These findings suggest that BBB breakdown occurs in areas of
      parasite sequestration in CM in African children.

PMID- 11442220
TI  - Impact of insecurity, the AIDS epidemic, and poverty on population health:
      disease patterns and trends in Northern Uganda.
AB  - A retrospective analysis of the discharge records of 186,131 inpatients admitted
      to six Ugandan hospitals during 1992-1998 was performed to describe the disease
      patterns and trends among the population of Northern Uganda. In all hospitals,
      malaria was the leading cause of admission and the frequency of admissions for
      malaria showed the greatest increase. Other conditions, such as malnutrition and
      injuries, mainly increased in the sites affected by civil conflict and massive
      population displacement. Tuberculosis accounted for the highest burden on
      hospital services (approximately one-fourth of the total bed-days), though it
      showed a stable trend over time. A stable trend was also observed for acquired
      immunodeficiency syndrome (AIDS), which is in contrast to the hypothesis that
      AIDS patients have displaced other patients in recent years. In conclusion,
      preventable and/or treatable communicable diseases, mainly those related to
      poverty and poor hygiene, represent the leading causes of admission and death,
      reflecting the socioeconomic disruption in Northern Uganda.

PMID- 11442221
TI  - Nutritional quality of germinated cowpea flour (Vigna unguiculata) and its
      application in home prepared powdered weaning foods.
AB  - Amino acid profiles, protein digestibility, corrected amino acid scores (PDCAAS),
      chemical scores, essential amino acid indexes, and calculated biological values
      of controlcowpea flour (CCF), germinated cowpea flour (GCF) prepared from cowpeas
      germinated at 25 degrees C for either 24 h or 48 h and weaning foods prepared
      from cowpea flours were determined. Locally available rice, cowpea flour, banana
      pumpkin slurry, and skim milk powder and sucrose in the ratio 35:35:15:15:5 were
      used to formulate weaning food containing not less than 15% protein. The
      ingredients were cooked into a slurry and oven-dried to produce flakes. The
      nutritional and sensory qualities of the weaning products were evaluated.
      Germination had little effect on the amino acid profile of cowpeas. In vitro
      protein quality and starch digestibility were improved in germinated cowpea
      flour. The PDCAAS of 24 h germinated cowpea flour (GCF) weaning food was higher
      (55.49%) than CCF-weaning food (46.74%). Vitamin A activity in 24 h GCF weaning
      food was higher than in CCF-weaning food. In vitro starch digestibilities of 24 h
      GCF and 48 h GCF-weaning foods were higher than that of CCF weaning food. The 24
      h GCF-weaning food which had a higher overall acceptability score by sensory
      panelist than 48 h GCF and CCF-weaning food is recommended for household
      consumption.

PMID- 11442222
TI  - Influence of processing conditions on the nutritive value of Ogi-baba, a Nigerian
      fermented sorghum gruel.
AB  - The effect of germination, cowpea fortification and fermentation on the chemical
      and amino acid composition of ogi-baba, a Nigerian fermented sorghum gruel was
      investigated. The lowest protein value of 1.4% was obtained in the traditionally
      prepared sample, while samples prepared from germinated, fortified sorghum had
      13%. The ash ranged from 0.9% to above 2%, while the fat was in the range of 1.2%
      to 2.8%. Generally, fortification, in addition to germination, improved the
      chemical composition of ogi-baba relative to the control sample. There was
      improvement in the amino acid profile of all the ogi-baba samples compared to the
      unprocessed sorghum grains. Lysine, a limiting amino acid in sorghum, increased
      more than 50% in ogi-baba. However, samples prepared using germinated sorghum
      without the addition of cowpeas had a lower lysine content.

PMID- 11442223
TI  - Total carotenoid and beta-carotene contents of forest green leafy vegetables
      consumed by tribals of south India.
AB  - Seventy edible wild forest green leafy vegetables (GLV) collected and consumed by
      tribals of Andhra Pradesh, India were analyzed for total carotenoids (TC) and
      beta carotene (BC) contents using high performance liquid chromatography (HPLC).
      The vitamin A activity expressed as retinol equivalents (RE) was calculated based
      on in vivo conversion factor given by WHO. The results of the study indicated
      that thirty-six GLV were found to have high vitamin A activity (0.87 to 2.34 RE)
      with TC and BC contents ranging from 12.22 to 36.13 and 5.21 to 14.05 mg %,
      respectively; thirty GLV had moderate vitamin A activity (0.36-0.8 RE) with TC
      and BC contents ranging from 10.60 to 31.33 and 2.19 to 4.78 mg %. Four GLV
      contained low vitamin A activity (0.07-0.32 RE); TC and BC contents ranging from
      5.12 to 13.13 and 0.40 to 1.94, respectively. The percent beta carotene in total
      carotenoids among the three groups of the GLV varied from 19.41 to 73.02, 11.11
      to 46.21 and 5.98 to 37.11, respectively.

PMID- 11442224
TI  - The cholesterol-lowering property of soybeans fed to rats is related to the
      fasting duration.
AB  - Numerous factors affect plasma cholesterol and, therefore, represent potential
      interferences with the specific effects of diet on lipid metabolism. After casein
      intake, serum cholesterol levels depend on many experimental conditions in rats,
      such as the type of casein, the presence or absence of cholesterol in the diet,
      the age and strain of rat, the diet composition, the nutritional status. The
      effect of fasting duration on selected parameters was studied in adult male
      Wistar rats fed a 20% casein and 1% cholesterol-based diet. No changes were
      observed in total serum, lipoproteins-B and HDL cholesterol and in triglyceride
      values after an 8 h-fast compared to non-fasted animals. A significant decrease
      was induced in total and lipoproteins-B cholesterol with a 12 h-fast. A prolonged
      fast resulted in a significant decrease in these parameters and in triglycerides
      and in HDL-cholesterol levels. Fasted animals fed heated soybean meal instead of
      casein did not display a marked decrease in serum lipids. It appeared that the
      fasting effect was more marked in animals fed casein than in animals fed
      soybeans. These results showed the importance of experimental conditions such as
      nutritional status of animals when blood samples are taken in studies of the
      hypocholesterolemic effect of soy protein compared to casein.

PMID- 11442225
TI  - Chemical, sensory and rheological properties of porridges from processed sorghum
      (Sorghum bicolor), bambara groundnut (Vigna subterranea L. Verdc) and sweet
      potato (Ipomoea batatas) flours.
AB  - The chemical, sensory and rheological properties of porridges made from blends of
      sprouted sorghum, bambara groundnuts and fermented sweet potatoes were examined.
      Sorghum and bambara groundnuts were sprouted for 48 h while sweet potatoes were
      fermented for the same period. Blends were formulated from the processed
      ingredients in the ratio of 60:40:0, 57:42:1, 55:44:1 and 52:46:2 (protein basis)
      of sorghum, bambara groundnuts and sweet potatoes. Porridges were prepared from
      the composite flours and the traditional sorghum complementary food. Standard
      assay methods were used to evaluate the flours for nutrient composition. The
      porridges were also tested for sensory properties and viscosity. Processing
      increased the levels of most of the nutrients evaluated. Relative to the sorghum
      traditional complementary food, the composite flours had higher levels of lipids,
      protein, ash, crude fiber and minerals (p < 0.05). The porridges from the
      composite flours were generally liked slightly by the panelists and were about
      seven times less viscous than the porridge from the traditional sorghum
      complementary food. Use of the composite flours, particularly the 52:46:2 blend,
      as a traditional complementary food should be encouraged in Nigeria especially
      with the increasing cost of commercial complementary foods.

PMID- 11442226
TI  - Tannin contents and protein digestibility of black grams (Vigna mungo) after
      soaking and cooking.
AB  - The objective of this research was to ascertain the effects of soaking black
      grams (Cultivar AARI-5732) in different salt solutions at different temperatures
      and different time periods, and different methods of cooking on the tannin
      content and protein digestibility. Tannin content of black grams was reduced to
      various extents by soaking at 30 degrees and 100 degrees C for different time
      periods. However, soaking at 100 degrees C increased the rate of extraction and
      reduced the extraction time of tannins. Soaking black grams in water at 100
      degrees C reduced tannins by 22.14% in 45 minutes whereas about 2.5 times more
      tannin was reduced after soaking in sodium bicarbonate solution with or without
      sodium chloride. Maximum improvement in protein digestibility was also observed
      after soaking black grams in sodium bicarbonate solution. Tannin contents were
      further reduced along with improvement in protein digestibility as a result of
      cooking.

PMID- 11442227
TI  - Influence of tryptophan supplementation of soy-based infant formulas on protein
      quality and on blood and brain tryptophan and brain serotonin in the rat model.
AB  - A 2-wk feeding study with weanling rats was conducted to investigate the effects
      of tryptophan supplementation of soy-based infant formulas on protein quality and
      on the levels of blood and brain tryptophan and brain serotonin and 5-HIAA (5
      hydroxyindole-3-acetic acid), a metabolite of serotonin. The powder and liquid
      concentrate forms of soy-based infant formulas obtained from four manufacturers
      were tested. The tryptophan contents of the test soy-based formulas (10.0-12.3
      mg/g protein) were considerably lower compared to those of human milk (17-19 mg/g
      protein). The infant formulas were fed as the sole source of protein in diets
      containing 8% protein, 20% fat, 5% cellulose and adequate amounts of minerals and
      vitamins. In general, supplementation of the diets containing test formulas with
      graded levels of L-tryptophan (0.1 or 0.2%) had no effect on protein quality
      indices based on rat growth such as PER (protein efficiency ratio), NPR (net
      protein ratio) and relative NPR (RNPR), but resulted in significant (p < 0.05)
      increases in the concentrations of tryptophan in the plasma and brain, and
      serotonin and 5-HIAA in brain of rats. The increased concentrations of brain
      tryptophan and 5-hydroxyindoles (serotonin + 5-HIAA) in rats fed tryptophan
      supplemented formulas compared to those fed unsupplemented formulas support the
      need for further research to investigate the influence of tryptophan
      supplementation of soy-based infant formulas on tryptophan metabolites and their
      potential related effects on sleep latency and neurobehavioral developments in
      infants.

PMID- 11442228
TI  - Retention of quality characteristics of dehydrated green leaves during storage.
AB  - Green leafy vegetables are the most underexploited class of vegetables despite
      high nutritional value. Reports on nutritional composition and storage of some of
      the fresh leaves are available but the storage behavior of dehydrated leaves
      apparently has not been studied. Therefore, in the present study, two green leafy
      vegetables, savoy beets (Beta vulgaris var. bengalensis) and fenugreek
      (Trigonella foenum graecum) were dehydrated in a low temperature drier and stored
      for 9 months under ambient and cold stored conditions after packaging in single
      or double layers of high density polyethylene film (200 gauge). The quality was
      determined on the basis of retention of beta-carotene, ascorbic acid and
      chlorophyll, and the extent of browning during storage. Retention of these
      quality characteristics depended on the crop and storage conditions. Double
      packed and cold stored samples of fenugreek retained 67% beta-carotene, whereas
      savoy beet leaves retained only 57% of the initial beta-carotene under similar
      conditions. Similarly, higher retention of ascorbic acid and chlorophyll, and
      lower browning was observed in double packed, cold stored samples. Results
      indicated the efficacy of double packed and cold stored samples over other
      combinations.

PMID- 11442229
TI  - Updated U.S. Public Health Service Guidelines for the Management of Occupational
      Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.
AB  - This report updates and consolidates all previous U.S. Public Health Service
      recommendations for the management of health-care personnel (HCP) who have
      occupational exposure to blood and other body fluids that might contain hepatitis
      B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
      Recommendations for HBV postexposure management include initiation of the
      hepatitis B vaccine series to any susceptible, unvaccinated person who sustains
      an occupational blood or body fluid exposure. Postexposure prophylaxis (PEP) with
      hepatitis B immune globulin (HBIG) and/or hepatitis B vaccine series should be
      considered for occupational exposures after evaluation of the hepatitis B surface
      antigen status of the source and the vaccination and vaccine-response status of
      the exposed person. Guidance is provided to clinicians and exposed HCP for
      selecting the appropriate HBV PEP. Immune globulin and antiviral agents (e.g.,
      interferon with or without ribavirin) are not recommended for PEP of hepatitis C.
      For HCV postexposure management, the HCV status of the source and the exposed
      person should be determined, and for HCP exposed to an HCV positive source,
      follow-up HCV testing should be performed to determine if infection develops.
      Recommendations for HIV PEP include a basic 4-week regimen of two drugs
      (zidovudine [ZDV] and lamivudine [3TC]; 3TC and stavudine [d4T]; or didanosine
      [ddI] and d4T) for most HIV exposures and an expanded regimen that includes the
      addition of a third drug for HIV exposures that pose an increased risk for
      transmission. When the source person's virus is known or suspected to be
      resistant to one or more of the drugs considered for the PEP regimen, the
      selection of drugs to which the source person's virus is unlikely to be resistant
      is recommended. In addition, this report outlines several special circumstances
      (e.g., delayed exposure report, unknown source person, pregnancy in the exposed
      person, resistance of the source virus to antiretroviral agents, or toxicity of
      the PEP regimen) when consultation with local experts and/or the National
      Clinicians' Post-Exposure Prophylaxis Hotline ([PEPline] 1-888-448-4911) is
      advised. Occupational exposures should be considered urgent medical concerns to
      ensure timely postexposure management and administration of HBIG, hepatitis B
      vaccine, and/or HIV PEP.

PMID- 11442231
TI  - Abattoir survey of dental defects in cull cows.
AB  - The teeth in the severed heads of 501 cull cows, all over 30 months of age, were
      examined at an abattoir in the north of England in 1997/98; 80 per cent of them
      were Friesians or Holsteins. Seventy-three animals (14.6 per cent) had one or
      more missing incisors, most of which were acquired losses. Rotation and
      overlapping of rostral teeth were also common, as was attrition. Congenitally
      absent first lower premolars, other missing teeth, large and often multiple
      interdental spaces, and a few cases of macrodontia, cavitation, multiple defects
      and fractures were observed in the cheek tooth arcades. There were some unusual
      patterns of premolar and molar attrition, often attributable to malocclusion, one
      result of which was the formation of a hook at the posterior extremity of the
      third maxillary molar.

PMID- 11442232
TI  - Confirmation of the presence of Mycoplasma bovis in Hungarian cattle with
      pneumonia resembling pleuropneumonia.
AB  - Cattle from several farms in Hungary were investigated for the presence of
      mycoplasmal infections after the discovery of pulmonary lesions in some animals
      at slaughter. The pneumonic lesions, which resembled those of contagious bovine
      pleuropneumonia (CBPP) macroscopically and histologically were found to be caused
      by Mycoplasma bovis and not Mycoplasma mycoides subspecies mycoides (MmmSC) which
      is the causative agent of CBPP. No other bacterial pathogens were isolated.
      Negative results in complement fixation tests also showed that there was no
      serological evidence of CBPP. PCR tests for the detection of the M mycoides
      cluster and specifically for MmmSC were also negative. However, PCR and
      bacteriological culture detected cases of M bovis and the pneumonias may
      therefore be attributed to this mycoplasma.

PMID- 11442233
TI  - Landscape fragmentation and foot-and-mouth disease transmission.

PMID- 11442234
TI  - Antibiotic resistance in avian bacteriological isolates.

PMID- 11442235
TI  - Hindlimb lameness: clinical judgement versus computerised symmetry measurement.

PMID- 11442236
TI  - Prevalence of antibodies to human adenovirus type 5 in Belgian cattle.

PMID- 11442237
TI  - Prevalence of Neospora caninum antibodies in wild ruminants from the Italian
      Alps.

PMID- 11442238
TI  - Surgical treatment of tethered spinal cord syndrome in a dog with
      myelomeningocele.

PMID- 11442239
TI  - Oral lesions in cattle and sheep.

PMID- 11442240
TI  - Oral lesions in cattle and sheep.

PMID- 11442241
TI  - Transplacental infection with PCV-2 associated with reproductive failure in a
      gilt.

PMID- 11442242
TI  - Postgraduate qualification in veterinary general practice.

PMID- 11442243
TI  - How DRGs hurt academic health systems.
AB  - BACKGROUND: Academic health centers continue their mission of clinical care,
      education, and research. This mission predisposes them to accept patients
      regardless of their individual clinical variation and financial risk. The purpose
      of this study is to assess the variation in costs and the attendant financial
      risk associated with these patients. In addition, we propose a new reimbursement
      methodology for academic health center high-end DRGs that better aligns financial
      risks. STUDY DESIGN: We reviewed clinical and financial data from the University
      of Michigan data warehouse for FY1999 (n = 39,804). The diagnosis-related groups
      were classified by volume (group 1, low volume to group 4, high volume). The
      coefficient of variation for total cost per admission was then calculated for
      each DRG classification. A regression analysis was also performed to assess how
      costs in the first 3 days estimated total costs. A hybrid methodology to estimate
      costs was then determined and its accuracy benchmarked against actual Medicare
      and Blue Cross reimbursements. RESULTS: Low-volume DRGs (< 75 annual admissions)
      had the highest coefficient of variation relative to each of the three other DRG
      classifications (moderate to high volume, groups 2, 3, and 4). The regression
      analysis accurately estimated costs (within 25% of actual costs) in 64.7% of
      patients with a length of stay > or = 4 days (n = 16,287). This regression fared
      well compared with actual FY 1999 DRG-based Medicare and Blue Cross
      reimbursements (n = 9,085 with length of stay > or = 4 days), which accurately
      reimbursed the University of Michigan Health System in only 43.9% of cases.
      CONCLUSIONS: Academic health centers receive a disproportionate number of
      admissions to low-volume, high-variation DRGs. This clinical variation translates
      into financial risk. Traditional risk management strategies are difficult to use
      in health care settings. The application of our proposed reimbursement
      methodology better distributes risk between payers and providers, and reduces
      adverse selection and incentive problems ("moral hazard").

PMID- 11442244
TI  - Malrotation of the small intestine with volvulus.

PMID- 11442245
TI  - Adherent thrombus from bleeding ulcer results in obstructing duodenal
      pseudotumor.

PMID- 11442246
TI  - The lateral approach to laparoscopic sigmoid colon resection.

PMID- 11442247
TI  - Liver hanging maneuver: a safe approach to right hepatectomy without liver
      mobilization.

PMID- 11442248
TI  - Oncotic balance: more decades of confusion?

PMID- 11442249
TI  - Effective treatment of head and neck squamous cell carcinoma by an oncolytic
      herpes simplex virus.
AB  - BACKGROUND: The prognosis of patients with advanced or recurrent head and neck
      squamous cell carcinoma remains poor despite refinements in multimodality
      therapies. This study evaluates the efficacy of a replication-competent,
      attenuated, oncolytic herpes simplex virus, NV1020, as a novel agent in the
      treatment of human head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN:
      Five different HNSCC lines were exposed to NV1020 in vitro at varying viral
      concentrations. The ability of the virus to lyse and replicate within these
      cancer cells in vitro was determined by cytotoxicity assay and plaque assay,
      respectively. Three HNSCC lines were grown in the subcutaneous flanks of athymic
      nude mice and treated with an intratumoral injection of NV1020 or saline as a
      control. Tumor dimensions were subsequently measured at serial time points and
      tumor volumes were calculated. Herpes simplex virus (HSV)-1 immunohistochemistry
      was performed on excised tumors to determine the efficacy of in vivo tumor
      infection by NV1020. RESULTS: NV1020 was highly cytotoxic in vitro to all five
      human HNSCC lines at a concentration of one infectious viral particle per cancer
      cell, and had variable cytotoxicity at a 100-fold lower concentration. Viral
      replication in vitro by NV1020 was efficient in four of five HNSCC lines with a
      greater than 200-fold increase in viral titers. Flank tumors treated with
      intratumoral injections of NV1020 resulted in significant regression of all
      tested HNSCC lines. HSV-1 immunohistochemistry of excised flank tumors treated
      with NV1020 demonstrated positive cytoplasmic staining and areas of tumor
      necrosis at 24 hours after injection. CONCLUSIONS: NV1020 is an oncolytic HSV
      that displays efficient replication and oncolysis in human HNSCC lines in vitro.
      Injection of NV1020 into murine flank tumors demonstrated effective tumor
      regression. Treatment of HNSCC with NV1020 is a promising form of therapy with
      potential clinical applicability in humans.

PMID- 11442250
TI  - The spectrum of vascular lesions in the mammary skin, including angiosarcoma,
      after breast conservation treatment for breast cancer.
AB  - BACKGROUND: With the general acceptance of lumpectomy, axillary staging, and
      radiotherapy as local treatment for infiltrating breast cancer, an appreciation
      is evolving for the spectrum of vascular lesions that occur in the mammary skin
      after this treatment. Most of these lesions develop within the prior radiation
      field after breast conservation treatment. STUDY DESIGN: A retrospective chart
      and slide review was conducted, consisting of five patients with cutaneous
      vascular lesions after breast conservation treatment for infiltrating breast
      cancer. RESULTS: The latent time interval from definitive treatment of breast
      cancer to the clinical recognition of vascular lesions ranged from 5 to 11 years.
      Two patients did not have either arm or breast edema, two patients had breast
      edema, and the fifth patient had arm edema. Lesions arising in the irradiated
      mammary skin included extensive lymphangiectasia (one), atypical vascular lesions
      (two), and cutaneous angiosarcoma (four). CONCLUSIONS: Atypical vascular lesions
      at the skin margins of mastectomy may be predictive of recurrence after resection
      of angiosarcoma. Excision of skin from the entire radiation field may be
      necessary to secure local control of the chest wall in patients with cutaneous
      angiosarcoma after therapeutic breast radiotherapy.

PMID- 11442251
TI  - Results of duct-to-mucosa pancreaticojejunostomy for pancreaticoduodenectomy
      Billroth I type reconstruction in 100 consecutive patients.
AB  - BACKGROUND: This study retrospectively analyzed 100 consecutive patients who
      underwent pancreaticoduodenectomy (PD) and pylorus-preserving PD (PPPD) with a
      Billroth I type reconstruction and pancreaticojejunostomy by duct-to-mucosal
      anastomosis using a continuous running suture. STUDY DESIGN: Seventy patients
      underwent PD and 30 patients PPPD for pancreatic cancer in 33, bile duct cancer
      in 28, ampullary or duodenal tumor in 22, chronic pancreatitis in 8, and other
      gastrointestinal cancer in 9. Postoperative pancreatic anastomotic leakage was
      diagnosed from skin excoriation around the drain site, and was defined as a high
      concentration of amylase in drainage fluid or leakage demonstrated on x-ray.
      RESULTS: The mortality rate was 2% overall (2.8% in PD, 0% in PPPD). The
      morbidity rate was 23% overall (12.8% in PD, 46.7% in PPPD). Pancreatic
      anastomotic leakage was 4.0% overall (2.8% in PD, 6.7% in PPPD).. The incidence
      in the ampullary or duodenal tumors was 9.1% overall (0% in PD, 14.3% in PPPD).
      Biliary leakage occurred in four patients, 4.0% overall (4.3% in PD, 3.3% in
      PPPD), intraabdominal hemorrhage in 2% (2.8% in PD, 0% in PPPD), and lethal
      anastomotic leakage in one patient, overall rate 1% (1.4% in PD, 0% in PPPD).
      Delayed gastric emptying had the highest morbidity and was seen exclusively in
      PPPD (39.3%). CONCLUSIONS: A simple continuous running suture and parachuting for
      duct-to-mucosal pancreaticojejunostomy makes pancreaticoduodenectomy a safe
      procedure, even in a Billroth I type reconstruction.

PMID- 11442252
TI  - Large cystic lesions of the liver in adults: a 15-year experience in a tertiary
      center.
AB  - BACKGROUND: Cystic lesions of the liver consist of a heterogeneous group of
      disorders and may present a diagnostic and therapeutic challenge. Large hepatic
      cysts tend to be symptomatic and can cause complications more often than smaller
      ones. STUDY DESIGN: We performed a retrospective review of adults diagnosed with
      large (> or = 4 cm) hepatic cystic lesions at our center, over a period of 15
      years. Polycystic disease and abscesses were not included. RESULTS: Seventy-eight
      patients were identified. In 57 the lesions were simple cysts, in 8 echinococcal
      cysts, in 8 hepatobiliary cystadenomas, and in 1 hepatobiliary
      cystadenocarcinoma. In four patients, the precise diagnosis could not be
      ascertained. Mean size was 12.1 cm (range, 4 to 30 cm). Most simple cysts were
      found in women (F:M, 49:8). Bleeding into a cyst (two patients) and infection
      (one patient) were rare manifestations. Percutaneous aspiration of 28 simple
      cysts resulted in recurrence in 100% of the cases within 3 weeks to 9 months
      (mean 4(1/2) months). Forty-eight patients were treated surgically by wide
      unroofing or resection (laparoscopically in 18), which resulted in low recurrence
      rates (11% for laparoscopy and 13% for open unroofing). Four of the eight
      patients with echinococcal cysts were symptomatic. All were treated by open
      resection after irrigation of the cavity with hypertonic saline. There was no
      recurrence during a followup period of 2 to 14 years. Hepatobiliary cystadenomas
      occurred more commonly in women (F:M, 7:1) and in the left hepatic lobe
      (left:right, 8:0). Seven were multiloculated. All were treated by open resection,
      with no recurrence, and none had malignant changes. Cystadenocarcinoma was
      diagnosed in a 77-year-old man, and was treated by left hepatic lobectomy.
      CONCLUSIONS: Large symptomatic simple cysts invariably recur after percutaneous
      aspiration. Laparoscopic unroofing can be successfully undertaken, with a low
      recurrence rate. Open resection after irrigation with hypertonic saline is a safe
      and effective treatment for echinococcal cysts. Hepatobiliary cystadenomas have
      predilection for women and for the left hepatic lobe. Malignant transformation is
      an uncommon but real risk. Open resection is a safe and effective treatment for
      hepatobiliary cystadenoma, and is associated with a low recurrence rate.

PMID- 11442253
TI  - Neoadjuvant transjugular intrahepatic portosystemic shunt: a solution for
      extrahepatic abdominal operation in cirrhotic patients with severe portal
      hypertension.
AB  - BACKGROUND: Major abdominal surgery, although technically feasible per se, can be
      contraindicated in some cirrhotic patients because of severe portal hypertension.
      The present study reports our experience of seven such patients who were prepared
      for major abdominal surgery by transjugular intrahepatic portosystemic shunt
      (TIPS). STUDY DESIGN: There were seven cirrhotic patients (six men and one woman
      aged 47 to 69 years) with portal hypertension. Portal hypertension was considered
      severe because of the presence of at least one of the following: history of
      variceal bleeding (five of seven patients), varices at risk of bleeding (red
      signs or cardial location of varices; four of seven patients), or intractable
      ascites (three of seven patients). The planned operations included colon,
      gastroesophageal, kidney, and aortic procedures in three, two, one, and one
      patient, respectively. Because portal hypertension was the leading cause of
      surgical contraindication, the following "two-step strategy" was applied to the
      seven patients: first, TIPS to control portal hypertension, followed, after a
      delay of at least 1 month, by abdominal surgery. RESULTS: The TIPS procedure was
      successfully performed in all patients without complications. The hepatic venous
      pressure gradient decreased from 18+/-5 to 9+/-5 mm Hg (p<0.01). All patients
      were operated on with a delay ranging from 1 month to 5 months after TIPS (2.9+/
      1.3 months; median 3 months). The planned operation was performed in six of the
      seven patients. One patient with cancer of the cardia did not have resection
      because of extensive abdominal spreading of the tumor. Intraoperative transfusion
      was necessary in only two patients. Operative mortality occurred in one patient,
      36 days after resection of a left colon cancer. CONCLUSIONS: The minimally
      invasive nature of TIPS allows us to propose the following two-step management of
      cirrhotic patients with severe portal hypertension needing abdominal surgery:
      decompression of the portal system by TIPS followed by elective surgery.

PMID- 11442254
TI  - Predictors of general surgical complications after heart transplantation.
AB  - BACKGROUND: Several studies have reported the incidence, morbidity, and mortality
      of general surgical conditions (GSCs) in orthotopic heart transplant (OHT)
      patients. The following is the largest reported series of such patients and the
      first study with sufficient patient numbers to formally evaluate peritransplant
      variables as risk factors for GSC development. STUDY DESIGN: A GSC was defined as
      a condition for which a general surgeon had been consulted or as a general
      surgical condition recognized at the time of autopsy. The records of 453
      consecutive patients who underwent OHT between 1981 and 1999 were reviewed to
      identify patients who developed a GSC. Kaplan-Meier actuarial analysis on this
      cohort, and univariate and multivariate logistic regression models applied to a
      subpopulation of 324 consecutive OHT patients between 1987 and 1997 were used to
      determine factors associated with and predictive of GSC after OHT. RESULTS: Of
      453 OHT patients, 371 (81.9%) were men, and the average age was 44.5 +/- 15
      (standard deviation) years. Median followup was 2,086 days (range 1 to 6,642
      days). Ninety-three patients (20.5%) developed 111 GSCs. Of these, 78 were men,
      and the average age was 49.9+/-10.2 years. There were 83 general surgical
      interventions. Actuarial analyses revealed that age greater than 50 years,
      pretransplant diagnosis of ischemic (PTDxI) versus nonischemic heart disease, and
      previous general surgical history were factors associated (p < 0.05) with a
      higher GSC incidence. Gender, more urgent transplant priority status,
      cardiopulmonary bypass time, total graft ischemic time, and intensive care unit
      length of stay were not associated with GSC. Factors associated with GSC on
      univariate analysis, with odds ratios (ORs) and 95% confidence intervals (CIs)
      included: age analyzed as a continuous variable (OR 1.04 per year; CI 1.01, 1.06
      per year; p = 0.0021), PTDxI (OR 2.40; CI 1.39, 4.15; p = 0.0016), and
      pretransplant general surgical history (OR 3.35; CI 1.65, 6.82; p = 0.0008).
      Multivariate analysis revealed that only pretransplant general surgical history
      (OR 3.27; CI 1.58, 6.76; p = 0.0004) and PTDxI (OR 2.37; CI 1.35, 4.16; p =
      0.0023) were associated with subsequent development of GSC. CONCLUSIONS: A
      pretransplant diagnosis of ischemic heart disease and previous history of a
      general surgical procedure are two independent risk factors that predispose OHT
      patients to development of GSC. Because GSC may arise insidiously in
      immunosuppressed patients, identification of OHT patients at higher risk for GSC
      will permit timely intervention decisions, decreasing morbidity and mortality in
      this challenging group of patients.

PMID- 11442255
TI  - What's new in obstetrics and gynecology.

PMID- 11442256
TI  - What's new in pediatric surgery.

PMID- 11442257
TI  - Doctor-patient communication in surgery: attitudes and expectations of general
      surgery patients about the involvement and education of surgical residents.
AB  - BACKGROUND: Education is a major function of academic medical centers. At these
      teaching institutions residents provide a substantial amount of care on medical
      and surgical services. The attitudes of patients about the training of surgical
      residents and the impact of residents on patients' perceptions of care in a
      surgical setting are unknown. STUDY DESIGN: Patients admitted to the
      gastrointestinal surgery service completed a 30-item survey designed for this
      study. Patients included in the study underwent operations and had a
      postoperative inpatient hospital stay. We analyzed patients' answers to determine
      frequency and correlations among answers. RESULTS: Two hundred patients
      participated in the study during a 7-month period between July 1999 and January
      2000. A majority of patients were comfortable having residents involved in their
      care (86%) and felt it was important to help educate future surgeons (91%). Most
      did not feel inconvenienced by being at a teaching hospital (71%) and felt they
      received extra attention there (74%). Patients were more willing to participate
      in resident education if they expected to have several physicians involved in
      their care, felt that they received extra attention, or if the teaching
      atmosphere did not inconvenience them. Despite the stated willingness of patients
      to help with surgical resident education, 32% answered that they would not want
      residents doing any of their operation. CONCLUSIONS: Surgical resident education
      is well received and considered important by patients. Patient orientation to the
      resident education process is vital to patients' perceptions of care and may
      render patients more willing to participate in educational activities.

PMID- 11442258
TI  - The Civil War's medical cadets: medical students serving the union.

PMID- 11442259
TI  - The use and misuse of neck dissection for head and neck cancer.

PMID- 11442260
TI  - A useful in vitro model for transport studies of alveolar epithelial barrier.

PMID- 11442261
TI  - Usefulness of the Kohlrausch-Williams-Watts stretched exponential function to
      describe protein aggregation in lyophilized formulations and the temperature
      dependence near the glass transition temperature.
AB  - PURPOSE: We studied the feasibility of using the Kohlrausch-Williams-Watts
      stretched exponential function (KWW equation) to describe protein aggregation in
      lyophilized formulations during storage. Parameters representing "mean
      aggregation time" (taua) and stretched exponential constant (betaa) were
      calculated according to the KWW equation by assuming that the time required for
      protein molecules to aggregate (tau) varies because of the fact that protein
      aggregation occurs at a rate that depends on the degree of protein deformation
      resulting from stresses created during freeze-drying. The temperature dependence
      of the parameters near the glass transition temperature was examined to discuss
      the possibility of predicting protein aggregation by accelerated testing.
      METHODS: Protein aggregation in lyophilized bovine serum gamma-globulin (BGG)
      formulations containing dextran or methylcellulose, at temperatures ranging from
      10 to 80 degrees C, was followed by size-exclusion chromatography. RESULTS: Non
      exponential BGG aggregation in lyophilized formulations could be described by the
      KWW equation. The taua and betaa, parameters changed abruptly around the NMR
      relaxation-based critical mobility temperature for formulations containing
      dextran and methylcellulose. In the glassy state, in contrast, the taua parameter
      of these formulations exhibited continuous temperature dependence. The parameter
      taur, as calculated from taua, and betaa, reflected differences in tau values
      between the two excipients. CONCLUSIONS: The results indicate that the parameter
      betaa is reflective of physical changes wihtin lyophilized formulations. Within
      the temperature range, during which no abrupt changes in betaa were observed,
      knowledge regarding the taua and betaa parameters allows the rate of protein
      aggregation to be predicted. The parameter taur was found to be useful in
      comparing the protein aggregation behavior of formulations having different taua
      and betaa values.

PMID- 11442262
TI  - Sodium chloride enhances the storage and conformational stability of BDNF and PEG
      BDNF.
AB  - PURPOSE: BDNF, a noncovalent homodimer, was modified by covalently attaching
      polyethylene glycol (PEG) with an average molecular weight of 20kDa to the N
      terminal methionine. Stability of modified BDNF (PEG-BDNF) in aqueous solution
      was compared to BDNF after storage at elevated temperature in the presence and
      absence of NaCl. METHODS: SDS-PAGE. Light Scattering and Size Exclusion
      Chromatography were used to assess conformational stability and chemical
      degradation. In addition, CD spectroscopy was used to follow changes in secondary
      and tertiary structures upon thermal stress of the protein. RESULTS: NaCl
      containing formulations are more stable than NaCl-free formulations. In NaCl-free
      formulations, the main degradation product of BDNF and PEG-BDNF had a molecular
      weight of monomer that was more chemically degraded than the dimer. Additionally,
      the degradation of PEG-BDNF occurred at an accelerated rate compared to BDNF in
      NaCl-free environments. CONCLUSIONS: The addition of NaCl to formulations
      enhances the shelf-life and conformational stability of both BDNF and PEG-BDNF.

PMID- 11442263
TI  - Investigation of solid-state reactions using variable temperature X-ray powder
      diffractrometry. I. Aspartame hemihydrate.
AB  - PURPOSE: The object of this study was to demonstrate the applicability of
      variable temperature X-ray powder diffractometry (XRD) to investigate solid-state
      reactions using aspartame as a model compound. METHODS: Aspartame exists as a
      hemihydrate (ASH) under ambient conditions and converts to aspartame anhydrate
      (ASA) at approximately 130 degrees C. ASA on further heating to approximately 180
      degrees C undergoes decomposition (intramolecular cyclization) to form a
      diketopiperazine derivative (DKP). The dehydration as well as the decomposition
      kinetics were studied isothermally at several temperatures. The unique feature of
      this technique is that it permits simultaneous quantification of the reactant as
      well as the product. RESULTS: While the dehydration of ASH appeared to follow
      first-order kinetics, the cyclization of ASA was a nucleation controlled process.
      The rate constants were obtained at various temperatures, which permitted the
      calculation of the activation energies of dehydration and cyclization from the
      Arrhenius plots. The activation energy of dehydration was also calculated
      according to the method described by Ng (Aust. J. Chem., 28:1169-1178, 1975) and
      the two values were in good agreement. CONCLUSIONS: The study demonstrates that
      XRD is an excellent complement to thermal analysis and provides direct
      information about the solid-states of various reaction phases.

PMID- 11442264
TI  - Influence of crystal structure on the tableting properties of sulfamerazine
      polymorphs.
AB  - PURPOSE: To understand the influence of polymorphic structure on the tableting
      properties of sulfamerazine. METHODS: Bulk powders of sulfamerazine polymorph I
      and of two batches. II(A) and II(B) of different particle size, of polymorph II
      were crystallized. The powders were compressed to form tablets whose porosity and
      tensile strength were measured. The relationships between tensile strength,
      porosity and compaction pressure were analyzed by the method developed by Joiris.
      E., et al. Pharm. Res. 15:1122-1130 (1998). RESULTS: The sensitivity of tensile
      strength to compaction pressure, known as the tabletability, follows the order. I
      >> II(A) > II(B) and the porosity at the same compaction pressure, which measures
      the compressibility, follows the order, I << II(A) < II(B). Therefore. the
      superior tabletability of I over II(A) or II(B) is attributed to its greater
      compressibility. Molecular simulation reveals slip planes in crystals of I but
      not in II. Slip planes provide I crystals greater plasticity and therefore
      greater compressibility and tabletability. Larger crystal size of II(B) than of
      II(A) leads to fewer contact points between crystals in the tablets and results
      in a slightly lower tabletability. CONCLUSIONS: Slip planes confer greater
      plasticity to crystals of I than II and therefore greater tabletability.

PMID- 11442265
TI  - Compaction properties of L-lysine salts.
AB  - PURPOSE: To examine the effects of salt form, i.e., different anions with a
      common cation (L-lysinium), on compaction properties and to identify the factors
      that determine the tensile strength of tablets. METHODS: L-Lysine salts with the
      following anions were compressed at various pressures: acetate, monochloride,
      dichloride, L-aspartate, L-glutamate (dihydrate), and L-lysine (zwitterionic
      monohydrate). The yield strength of each salt was evaluated from the "out-of-die"
      Heckel plot. RESULTS: At low compaction pressures, the tensile strength of the
      compacts increases linearly with increasing compaction pressure. Simultaneously.
      the compact tensile strength decreases exponentially with increasing yield
      strength of the salt. However, at high compaction pressures, the compact tensile
      strength is determined by the interparticulate bonding strength and not by the
      yield strength. The compact tensile strength, extrapolated to zero porosity,
      increases linearly with increasing melting temperature of the salts. CONCLUSIONS:
      The counterion affects the tableting properties of L-lysine salts. The tensile
      strength is controlled by both the yield strength and the interparticulate
      interaction strength with the former predominant at low compaction pressures and
      the latter predominant at high compaction pressures. The melting temperature of
      each L-lysine salt is a good indicator of the tensile strength of its compacts at
      zero porosity.

PMID- 11442266
TI  - Incorporation of the model drug ubidecarenone into solid lipid nanoparticles.
AB  - PURPOSE: The impact of drug incorporation on melt-homogenized tripalmitin
      nanoparticles is investigated with ubidecarenone as a model drug. The dispersions
      are studied with respect to their drug loading capacity, localization and
      physical state of the drug as well as to potential changes of the nanoparticle
      properties due to interactions between drug and triglyceride matrix. METHODS: The
      investigations were carried out using photon correlation spectroscopy,
      differential scanning calorimetry, synchrotron radiation X-ray diffraction,
      ultracentrifugation, and cryo- and freeze-fracture transmission electron
      microscopy. RESULTS: Ubidecarenone can be incorporated into the dispersions in
      concentrations higher than 50% of the dispersed phase. The drug is associated
      with the nanoparticles such that small drug amounts are bound tightly to the
      carrier matrix while excess drug adheres as a liquid phase to the crystalline
      particles. Drug incorporation lowers the crystallization and melting temperature
      of the particle matrix and accelerates the transition of the triglyceride into
      the stable beta-polymorph after crystallization. CONCLUSIONS: Drug incorporation
      may significantly alter important physicochemical parameters of solid lipid
      nanoparticles. Slow release of ubidecarenone may only be possible for the
      fraction of drug which is tightly bound to the matrix while the liquid fraction
      should be rapidly released.

PMID- 11442267
TI  - An investigation into the surface deposition of progesterone on poly (d,l-)
      lactic acid microspheres using micro-thermal analysis.

PMID- 11442268
TI  - An in situ dissolution study of aspirin crystal planes (100) and (001) by atomic
      force microscopy.
AB  - PURPOSE: To observe in situ and on individual aspirin crystal faces the
      comparative rates and processes of dissolution of the dominant faces. METHODS:
      The kinetics of the dissolution rate of two aspirin crystal planes (001) and
      (100) under 0.05M HCl are studied in situ at room temperature using Atomic Force
      Microscopy. The dissolution process of each crystal plane was followed by
      observed changes in topographic features. RESULTS: The results revealed that
      crystal plane (001) dissolves by receding step edges, and has a dissolution rate
      of 0.45 nm s(-1). Conversely. plane (100) displays crystal terrace sinking at an
      average rate of 2.93 nm s(-1). Calculated intrinsic dissolution values (g s(-1)
      cm(-2)) for planes (001) and (100) are 1.37 x 10(-7) gs(-1) cm(-2) and 8.36 x 10(
      7) gs(-1) cm(-2), respectively. CONCLUSIONS: These values indicate that the rate
      of flux of material from plane (100) is approximately six times greater than that
      from plane (001), under 0.05M HCl. Interpretation of the data, based upon
      intrinsic dissolution rates and dissolution rate velocities, correlate with
      reported variations in the dissolution behavior of commercial aspirin products.
      These observations illustrate the suitability of the technique for characterizing
      the dissolution behavior of crystalline drugs.

PMID- 11442269
TI  - Transport properties of ionic drugs in the ammonio methacrylate copolymer
      membranes.
AB  - PURPOSE: Ammonio methacrylate copolymer is a pharmaceutical excipient widely used
      as a coating material for encapsulation of pellet and tablet dosage forms.
      Because of the charged ammonio function groups within the polymer, ionic drugs
      may interact with the coating film while transporting through it. The kinetic
      swelling and drug permeation properties of the ammonio methacrylate copolymer
      membranes were studied to delineate the effect of ionic interaction between the
      ionic drugs and the membranes. METHODS: The pH and ionic strength of the
      solutions and the charged properties of drugs were varied to study the effects on
      the transport properties through the membranes. Ambroxol was chosen as a model
      cationic drug and aspirin as a model anionic drug. RESULTS: The degree of
      membrane swelling in the drug-free solution decreases as the ionic strength
      increases but it is irrelevant to the pH. With the presence of ionic drugs, the
      degree of membrane swelling is affected by the drug species as well as the pH of
      the solutions in addition to the effect of ionic strength. The degree of swelling
      for a membrane in a solution containing aspirin is higher at a lower pH and
      ambroxol is lower at a lower pH. Aspirin experiences a three-stage permeation and
      ambroxol a two-stage one. The ion-exchange reaction between the anionic
      carboxylic groups in aspirin and the cationic ammonio groups in the membranes
      results in a slow permeation stage during the transient state. The pseudo steady
      state permeability for each drug follows the trend as the degree of membrane
      swelling in the drug media at various pH and ionic strengths. However, it is much
      higher for aspirin than ambroxol although the degree of membrane swelling is
      higher in an ambroxol solution than that in an aspirin solution. The permeability
      of ambroxol through the membrane is largely reduced because of the Donnan
      exclusion effect. CONCLUSIONS: The interaction between ionic drugs with the
      cationic groups in the membranes affects the ionic strength of the solutions and
      results in a pH-dependent degree of swelling. The ionic interaction also
      determines the drug permeation rates as well as the transient permeation
      behaviors.

PMID- 11442270
TI  - Iontophoretic delivery of 5-aminolevulinic acid (ALA): effect of pH.
AB  - PURPOSE: To examine the iontophoretic delivery of ALA as a function of pH and to
      determine the principal mechanisms responsible for its electrotransport. METHODS:
      Anodal iontophoretic transport of ALA was measured as a function of its
      concentration and pH of the donor solution. Experiments were performed in vitro
      using skin excised from porcine ears as the membrane. To deduce mechanism, the
      concomitant transport of the electroosmotic marker, mannitol, was also assessed.
      RESULTS: ALA iontophoresis at pH 7.4 is a linear function of concentration over
      the range 1-100 mM. The mechanism was deduced to be electroosmosis. By reducing
      the pH from 7.4 to 4.0, the dominant mechanism of ALA transport was shifted from
      electroosmosis to electrorepulsion as the skin's net negative charge was
      progressively neutralized. However, the total delivery of the compound was not
      altered by lowering the pH suggesting that the increased electrorepulsive
      contribution was essentially balanced by the concomitantly reduced
      electroosmosis. CONCLUSIONS: Significant ALA delivery at pH 7.4 can be achieved
      by increasing the drug concentration in the anodal formulation to 100 mM.
      Lowering the pH does not result in increased ALA transport. Alternative
      strategies are therefore required to maximize and optimize ALA delivery by
      iontophoresis.

PMID- 11442271
TI  - Formulation and evaluation of a folic acid receptor-targeted oral vancomycin
      liposomal dosage form.
AB  - PURPOSE: To demonstrate utility of folic acid-coated liposomes for enhancing the
      delivery of a poorly absorbed glycopeptide, vancomycin. via the oral route.
      METHODS: Liposomes prepared as dehydration-rehydration vesicles (DRVs) containing
      vancomycin were optimized for encapsulation efficiency and stability. A folic
      acid-poly(ethylene oxide)-cholesterol construct was synthesized for adsorption at
      DRV surfaces. Liposomes were characterized by differential scanning calorimetry
      (DSC) and assessed in vitro in the Caco-2 cell model and in vivo in male Sprague
      Dawley rats. Non-compartmental pharmacokinetic analysis of vancomycin was
      conducted after intravenous and oral administration of solution or liposome
      encapsulated vancomycin with or without 0.05 mole ratio FA-PEO-Chol adsorbed at
      liposome surfaces. RESULTS: Optimal loading of vancomycin (32%) was achieved in
      DRVs of DSPC:Chol:DCP, 3:1:0.25 mole ratio (m.r.) after liposome extrusion.
      Liposomes released less than 40% of the entrapped drug after 2 hours incubation
      in simulated gastrointestinal (GI) fluid and simulated intestinal fluid
      containing a 10 mM bile salt cocktail. Incorporation of FA-PEO-Chol in liposomes
      increased drug leakage by 20% but resulted in a 5.7-fold increase in Caco-2 cell
      uptake of vancomycin. Liposomal delivery significantly increased the area under
      the curve of oral vancomycin resulting in a mean 3.9-fold and 12.5-fold increase
      in relative bioavailability for uncoated and FA-PEO-Chol-coated liposomes,
      respectively, compared with an oral solution. CONCLUSIONS: The design of FA-PEO
      Chol-coated liposomes resulted in a dramatic increase in the oral delivery of a
      moderate-size glycopeptide in the rat compared with uncoated liposomes or oral
      solution. It is speculated that the cause of the observed effect was due to
      binding of liposome-surface folic acid to receptors in the GI tract with
      subsequent receptor-mediated endocytosis of entrapped vancomycin by enterocytes.

PMID- 11442272
TI  - Novel polymeric micelles based on the amphiphilic diblock copolymer poly(N-vinyl
      2-pyrrolidone)-block-poly(D,L-lactide).
AB  - PURPOSE: The purpose of this work was to synthesize a new amphiphilic diblock
      copolymer of poly(N-vinyl-2-pyrrolidone and poly(D,L-lactide) (PVP-b-PDLLA)
      capable of self-assembling into polymeric micelles with multiple binding sites
      and high entrapment efficiency. METHODS: The copolymer was synthesized by ring
      opening polymerization of D,L-lactide initiated by potassium PVP hydroxylate. It
      was characterized by gel permeation chromatography, 1H- and 13C-NMR spectroscopy.
      The ability of the copolymer to self-assemble was demonstrated by dynamic and
      static light scattering, spectrofluorimetry and 1H-NMR. The hydrophobic model
      drug indomethacin was incorporated into the polymeric micelles by a dialysis
      procedure. Results. A series of amphiphilic diblock copolymers based on PVP-b
      PDLLA were successfully synthesized. The critical association concentrations in
      water were low, always below 15 mg/L. Micellar size was generally bimodal with a
      predominant population between 40 and 100 nm. PVP-b-PDLLA micelles were
      successfully loaded with the poorly water-soluble drug indomethacin and
      demonstrated an entrapment efficiency higher than that observed with control
      poly(ethylene glycol)-b-PDLLA micelles. It was hypothesized that specific
      interactions with the hydrophilic outer shell could contribute to the increase in
      drug loading. CONCLUSION: PVP-b-PDLLA micelles appear to exhibit multiple binding
      sites and thus represent a promising strategy for the delivery of a variety of
      drugs.

PMID- 11442273
TI  - Binding and internalization of an LFA-1-derived cyclic peptide by ICAM receptors
      on activated lymphocyte: a potential ligand for drug targeting to ICAM-1
      expressing cells.
AB  - PURPOSE: The interaction of cell-adhesion molecules LFA-1/ICAM-1 is critical for
      many inflammatory and immune responses. Blockades of this interaction using
      antibodies or peptide analogs are being developed as therapeutic approaches for
      inflammatory and autoimmune diseases. The aim of this study is to examine the
      binding and internalization mechanisms of LFA-1 peptide [cLAB.L or cyclo-(1,12)
      PenITDGEATDSGC] mediated by ICAM receptors on the surface of lymphocytes.
      METHODS: The binding and internalization of cLAB.L were evaluated using
      fluorescence-labeled cLAB.L on activated Molt-3 cells, measured by flow
      cytometry. Confocal fluorescence microscopy was also used to image the
      distribution of peptide binding and internalization. RESULTS: The binding of FITC
      cLAB.L exhibited bimodal cell distribution and was enhanced by Ca2+ and Mg2+.
      Marked differences in peptide binding were found between 37 and 4 degrees C, as
      well as between activated and non-activated cells. Unlabeled peptide, low
      temperature, and the absence of cell activation suppress the peptide binding. The
      presence of peptide in the cytoplasm was detected in 37 but not 4 degrees C
      binding. Peptide cLAB.L inhibited the binding of monoclonal antibodies to domain
      D1 of ICAM-1 and domain D1 of ICAM-3. CONCLUSIONS: Peptide cLAB.L can bind to the
      D1-domain of ICAM-1 and, to a lesser extent, to ICAM-3 on activated T-cells.
      Peptide binding indicates responses to the multiple and dynamic states of
      activated receptor ICAMs, this peptide may also be internalized by ICAM receptors
      on T-cells. This work suggests that cLAB.L has a therapeutic potential to target
      drugs to ICAM-1 expressing cells including autoreactive lymphocytes and inflamed
      tissues.

PMID- 11442274
TI  - DRV liposomal bupivacaine: preparation, characterization, and in vivo evaluation
      in mice.
AB  - PURPOSE: To evaluate the dehydration-rehydration technique to prepare a
      formulation of liposomal bupivacaine, and to assess its analgesic efficacy.
      METHODS: Bupivacaine hydrochloride (BUP) was encapsulated into dehydration
      rehydration vesicles (DRV) of varying phospholipid (PL) compositions. Two bilayer
      forming phospholipids were used, the "fluid" dimyristoyl-phosphatidylcholine and
      the "solid" distearoyl-phosphatidylcholine (DSPC), with 20 or 40 mol%
      cholesterol, in the presence of bupivacaine at a 1.28 or 0.64 BUP/PL mole ratio.
      After rehydration, drug/lipid ratios were determined. The formulation with the
      highest drug/lipid ratio (DSPC/cholesterol in an 8:2 mole ratio prepared in the
      presence of bupivacaine in a 1.28 BUP/PL mole ratio) was adjusted to a final
      bupivacaine concentration of 3.5% or 0.5%. The duration of skin analgesia after
      subcutaneous injection in mice produced by these formulations was compared with
      the conventional administration of a plain 0.5% solution of BUP. In addition, the
      concentration of residual bupivacaine at the injection site was followed for 96
      h. RESULTS: The relatively low organic solvent/aqueous phase and membrane/aqueous
      phase partition coefficients, together with liposomal trapped volume and BUP/PL
      mole ratio, indicated that most of the drug was encapsulated in the intraliposome
      aqueous phase of the DRV. The DSPC/cholesterol 8:2 mole ratio had the best drug
      encapsulation (BUP/PL = 0.36). Compared to plain BUP, these BUP-DRV produced
      significant prolongation of analgesia, which is explained by longer residence
      time of the drug at the site of injection. CONCLUSIONS: Bupivacaine-DRV may have
      a role in achieving safe, effective, and prolonged analgesia in humans.

PMID- 11442275
TI  - Lyophilized lecithin based oil-water microemulsions as a new and low toxic
      delivery system for amphotericin B.
AB  - PURPOSE: To develop and investigate lecithin based oil-water microemulsions as
      potential amphotericin B (AmB) delivery systems and to evaluate their in vivo
      acute toxicity. METHODS: AmB was added to the microemulsion and its location was
      evaluated by partitioning studies and UV-visible spectrophotometric analysis of
      the drug. Both, non-lyophilized and reconstituted microemulsions were
      characterised and assessed for their stability. Single-dose acute toxicity of the
      AmB microemulsion was studied on male albino Webster-derived CD-1 mice and
      compared with Fungizone. RESULTS: The studies performed showed that AmB was
      intercalated on the oil-water interface of the microemulsion as a complex formed
      with lecithin molecules. AmB addition did not seem to modify the rheological
      properties of the original system, but had an effect on its particle size
      distribution. Lyophilization of the microemulsion led to an oily cake, easily
      reconstituted and stable at the conditions studied. Single-dose acute toxicity
      studies proved that the LD50 of AmB microemulsions was of 4 mg kg(-1) of animal
      weight, compared with 1 mg kg(-1) found for Fungizone. CONCLUSIONS: Lyophilized
      lecithin based oil-water microemulsions appear to be valuable systems for the
      delivery of AmB in terms of easy and low-cost manufacturing, stability and safety
      compared with the formulations already in market.

PMID- 11442276
TI  - Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft
      poly(lactide-co-glycolide): evaluation of antibody response after oral and nasal
      application in mice.
AB  - PURPOSE: Aim of the study was the evaluation of the potential of novel tetanus
      toxoid (TT) loaded nanoparticles (NP) for electing an immune response in mice
      against TT. METHODS: Six week-old female Balb/c mice were immunized by oral
      (p.o.), nasal (i.n.) and intraperitoneal (i.p.) application of TT NP loaded by
      adsorption. As polymer a novel polyester, sulfobutylated poly(vinyl alcohol)
      graft-poly(lactide-co-glycolide), SB(43)-PVAL-g-PLGA was used. Blood samples were
      collected 4 and 6 weeks after immunization and assayed for serum IgG- as well as
      IgA antibody titers by ELISA. NP formulations varying in size and loading were
      compared to alum adsorbates as well as to TT solutions. RESULTS: Both, p.o. and
      i.n. administration of TT associated NP increased serum titers up to 3 x 10(3)
      (IgG) and 2 x 10(3) (IgA). While small NP induced significantly higher titers
      then larger ones after oral administration, intermediate NP induced antibodies
      after nasal application. Of the mucosal routes investigated, i.n. seems to be
      more promising compared to p.o. immunization. CONCLUSIONS: Antigen loaded NP
      prepared from surface modified polyesters combined with CT show considerable
      potential as a vaccine delivery system for mucosal immunization. The results
      warrant further experiments to explore in more detail the potential use of NP as
      mucosal vaccine delivery system.

PMID- 11442277
TI  - Probe calibration in transient microdialysis in vivo.
AB  - PURPOSE: We examine the theoretical basis for calibrating microdialysis probes in
      vivo for pharmacokinetic experiments in which the extracellular analyte
      concentrations vary in time. METHODS: A software package, MICRODIAL. was used to
      simulate microdialysis for illustrative transient situations with linear
      concentration dependence. RESULTS: For a constant distant extracellular analyte
      concentration. the calibration factor (extraction fraction, Ed) exhibits a mass
      transfer transient associated with the development of spatial concentration
      profiles within the tissue and the probe. Processes clearing the analyte from the
      extracellular fluid (ECF) strongly influence the rapidity of approach to steady
      state and affect the magnitude of the steady-state calibration factor, Ess(d).
      For situations in which the distant ECF concentration varies in time as a result
      of exchange with the plasma compartment, different time profiles of the distant
      ECF and plasma concentrations yield different transient E(d). For the linear,
      transient cases examined, the area-under-the-curve (AUC 0-infinity) time integral
      of the distant ECF concentration was found to be proportional to the outflow
      dialysate concentration-time integral with Ess(d) being the proportionality
      constant. CONCLUSIONS: The options for calibrating microdialysis probes in solid
      tissues appear limited under non-steady state conditions; however, AUC integrals
      for linear systems may be determined by continuous microdialysis sampling and
      steady-state probe calibration approaches.

PMID- 11442278
TI  - Dermal pharmacokinetics of microemulsion formulations determined by in vivo
      microdialysis.
AB  - PURPOSE: To investigate the potential of improving dermal drug delivery of
      hydrophilic and lipophilic substances by formulation in microemulsion vehicles
      and to establish a reliable pharmacokinetic model to analyze cutaneous
      microdialysis data. METHODS: After a topical application of microemulsions,
      commercially available creams, and a hydrogel, unbound cutaneous concentrations
      of lidocaine and prilocaine were determined by in vivo microdialysis in rats.
      Recovery was monitored during the experiments via retrodialysis by calibrator.
      RESULTS: The presented pharmacokinetic model provided an excellent fit of the
      microdialysis concentration-time curves with reliable estimation of absorption
      coefficient and lag time. The microemulsion formulations were shown to increase
      the absorption coefficient of lidocaine more than eight times (753 microg/l/min)
      compared with a conventional oil-in-water emulsion-based cream (89 microg/l/min)
      and prilocaine hydrochloride almost two times (8.9 microg/l/min) compared with
      hydrogel (5.2 microg/l/min). CONCLUSIONS: The microemulsion formulations can be
      applied to increase dermal drug delivery of both the hydrophilic and lipophilic
      model drug. The pharmacokinetic model presented in this report is, to the
      author's knowledge, the first example in the literature, providing reliable
      estimation of cutaneous absorption coefficient and lag time from microdialysis
      data of topically applied substances.

PMID- 11442279
TI  - Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in Caco
      2 cells--potential role in carcinogen bioinactivation.
AB  - PURPOSE: Dietary flavonoids, present in fruits, vegetables and beverages have
      been demonstrated to be protective in cancer. Recently, we showed that the
      flavonoid chrysin induced UDP-glucuronosyltransferase (UGT) activity and
      expression in the human intestinal cell line Caco-2. In the present study, we
      determined the specific UGT isoform(s) induced and whether this induction
      facilitates glucuronidation and potential detoxification of the colon carcinogen
      2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP). METHODS:
      The induction was studied by immunoblot analysis with UGT isoform-specific
      antibodies, by Northern blot analysis and using quercetin as an isoform-specific
      catalytic probe. Glucuronidation of N-hydroxy-PhIP was characterized using both
      recombinant UGTs and control and chrysin-treated microsomes. RESULTS: Western
      blot analysis showed that pretreatment of Caco-2 cells with 25 microM chrysin
      induced UGT1A1 without affecting the expression of UGTs 1A6, 1A9 and 2B7.
      Northern blot analysis showed markedly increased expression of UGT1AI mRNA after
      chrysin treatment. Similarly, glucuronidation of quercetin was greatly increased
      in a UGT1A1-specific way. The induction of UGT1A1 in the Caco-2 cells resulted in
      a 10-fold increase in the glucuronidation of N-hydroxy-PhIP. CONCLUSION: Dietary
      flavonoid-mediated induction of intestinal UGT1A1 may be important for the
      glucuronidation and detoxification of colon and other carcinogens as well as for
      the presystemic metabolism of therapeutic drugs.

PMID- 11442280
TI  - Biorelevant dissolution testing to predict the plasma profile of lipophilic drugs
      after oral administration.
AB  - PURPOSE: To quantitatively compare in vitro dissolution data in biorelevant and
      compendial media, to investigate whether in vitro differences are reflected in
      the simulated plasma profile and to specify under which circumstances prediction
      of the plasma profile of orally administered lipophilic drugs can be achieved.
      METHODS: Previously published dissolution data from seven products of four
      lipophilic drugs were compared using the first order model, the RRSBW
      distribution, and a model based on the Noyes-Whitney theory. Simulated plasma
      profiles were then obtained using a model-dependent approach. Simulated and
      observed plasma profiles were compared with the difference factor, f1. RESULTS:
      No model consistently provided the best fit to the in vitro data, which varied
      significantly with medium composition. Prediction of the plasma profile was
      possible (9.6 < or = f1 < or = 34.2) in seven out of eleven cases. CONCLUSIONS:
      Although prediction of the plasma profile of lipophilic drugs solely on the basis
      of in vitro data remains an ambitious target, this study shows that the plasma
      profile of a lipophilic drug can be predicted with appropriate in vitro
      dissolution data, provided that the absolute bioavailability of the drug is known
      and the drug has dissolution limited absorption.

PMID- 11442281
TI  - Role of biantennary glycans and genetic variants of human alpha1-acid
      glycoprotein in enantioselective binding of basic drugs as studied by high
      performance frontal analysis/capillary electrophoresis.
AB  - PURPOSE: To establish a clear understanding of the role of biantennary branching
      glycans and genetic variants of alpha1-acid glycoprotein (AGP) in
      enantioselective bindings of basic drug. METHODS: Human native AGP was separated
      using concanavalin A affinity chromatography into two subfractions, the
      unretained fraction (UR-AGP, defect of biantennary glycan) and the retained
      fraction (R-AGP, possessing biantennary glycan(s)). Imminodiacetate-copper (II)
      affinity chromatography was used to separate human native AGP into A variant and
      a mixture of F1 and S variants (F1*S variants). The mixed solutions of the (R)-
      or (S)-isomer of the model drugs (15 microM disopyramide (DP) or 30 microM
      verapamil (VER)) and 40 microM of respective AGP species were subjected to high
      performance frontal analysis/capillary electrophoresis (HPFA/CE) to determine the
      unbound drug concentrations. RESULTS: The unbound concentrations (Cu) of DP in UR
      AGP solutions were lower than those in R-AGP solutions, whereas there was no
      significant difference in the enantiomeric ratios (Cu(R)/Cu(S)) of DP between UR-
      and R-AGP solutions. In case of genetic variant, the Cu(R)/Cu(S) values of DP in
      F1*S and A solutions were 1.07 and 2.37, respectively. On the other hand, the
      enantiomeric ratio of VER in F1*S and A variant solutions were 0.900 and 0.871,
      respectively. CONCLUSIONS: The biantennary glycan structures are related to
      binding affinity of DP to AGP, but not responsible for the enantioselectivity.
      Genetic variants give significant effect on the enantioselectivity in DP binding,
      but not in VER binding.

PMID- 11442282
TI  - Variability in the bioavailability of phenytoin capsules in males and females.
AB  - PURPOSE: To determine inter-lot and intra-subject variability in the
      bioavailability of the 100 mg extended phenytoin sodium capsules. In addition, to
      determine the effect of gender and menstrual cycle on phenytoin bioavailability.
      METHODS: Three different lots of extended phenytoin sodium capsules were given to
      12 healthy male and 12 healthy female subjects in a crossover fashion. One of the
      lots was also given a second time to each subject. Plasma phenytoin was
      determined, using an HPLC assay, in samples collected over a 73-hr period after
      each dose. RESULTS: The mean Cmax for the four administrations ranged from 1.71
      1.79 microg/ml and mean AUC(0-infinity) values from ranged 53.0-54.1
      microg*hr/ml. The elimination half-life was 3 hr shorter, and the AUC(0-infinity)
      adjusted for the mg/kg dose was 30% lower for females. Average bioequivalence was
      demonstrated between the three lots for both Cmax and AUC(0-infinity) based on
      the BE limit of 80-125%. Further, all confidence intervals of AUC(0-infinity)
      fell within the limit of 90-111%. There were no differences in the confidence
      limits for Cmax and AUC(0-infinity) determined separately for males and females.
      Also, there was no difference in the mean Cmax or AUC(0-infinity) for females
      when analyzed as a function of the week of their menstrual cycle. Individual
      bioequivalence was demonstrated between three lots of phenytoin using the
      constant-scaled method, but not the reference-scaled method. CONCLUSIONS: There
      was very little difference in the bioavailability of the three lots of phenytoin.
      Females exhibited a lower AUC(0-infinity) than males after adjustment of dose for
      body weight, but their inclusion in the study did not affect the assessment of
      bioequivalence. When dose was not adjusted for body weight, no difference in
      AUC(0-infinity) was seen between males and females.

PMID- 11442283
TI  - Influence of tailor-made additives on etching patterns of acetaminophen single
      crystals.

PMID- 11442284
TI  - Cryopreservation enables long-term storage of 9-(2-phosphonylmethoxyethyl)adenine
      prodrug-loaded reconstituted lactosylated high-density lipoprotein.

PMID- 11442285
TI  - Rapid and sensitive assay of tumor necrosis factor-alpha gene transcription.

PMID- 11442286
TI  - Time-frequency parameters of the surface myoelectric signal for assessing muscle
      fatigue during cyclic dynamic contractions.
AB  - The time-dependent shift in the spectral content of the surface myoelectric
      signal to lower frequencies has proven to be a useful tool for assessing
      localized muscle fatigue. Unfortunately, the technique has been restricted to
      constant-force, isometric contractions because of limitations in the processing
      methods used to obtain spectral estimates. A novel approach is proposed for
      calculating spectral parameters from the surface myoelectric signal during cyclic
      dynamic contractions. The procedure was developed using Cohen class time
      frequency transforms to define the instantaneous median and mean frequency during
      cyclic dynamic contractions. Changes in muscle length, force, and electrode
      position contribute to the nonstationarity of the surface myoelectric signal.
      These factors, unrelated to localized fatigue, can be constrained and isolated
      for cyclic dynamic contractions, where they are assumed to be constant for
      identical phases of each cycle. Estimation errors for the instantaneous median
      and mean frequency are calculated from synthesized signals. It is shown that the
      instantaneous median frequency is affected by an error slightly lower than that
      related to the instantaneous mean frequency. In addition, we present a sample
      application to surface myoelectric signals recorded from the first dorsal
      interosseous muscle during repetitive abduction/adduction of the index finger
      against resistance. Results indicate that the variability of the instantaneous
      median frequency is related to the repeatability of the biomechanics of the
      exercise.

PMID- 11442287
TI  - Feedback control of a biodynamical model of HIV-1.
AB  - We describe a continuous differential equation model of the interaction dynamics
      of HIV-1 and CD4 and CD8 lymphocytes in the human body. We demonstrate several
      methods of stable control of the HIV-1 population using an external feedback
      control term that is analogous to the introduction of a therapeutic drug regimen.
      We also show how the immune system components can be bolstered against the virus
      through a feedback control approach.

PMID- 11442288
TI  - Reconstructing spatio-temporal activities of neural sources using an MEG vector
      beamformer technique.
AB  - We have developed a method suitable for reconstructing spatio-temporal activities
      of neural sources by using magnetoencephalogram (MEG) data. The method extends
      the adaptive beamformer technique originally proposed by Borgiotti and Kaplan to
      incorporate the vector beamformer formulation in which a set of three weight
      vectors are used to detect the source activity in three orthogonal directions.
      The weight vectors of the vector-extended version of the Borgiotti-Kaplan
      beamformer are then projected onto the signal subspace of the measurement
      covariance matrix to obtain the final form of the proposed beamformer's weight
      vectors. Our numerical experiments show that both spatial resolution and output
      signal-to-noise ratio of the proposed beamformer are significantly higher than
      those of the minimum-variance-based vector beamformer used in previous
      investigations. We also applied the proposed beamformer to two sets of auditory
      evoked MEG data, and the results clearly demonstrated the method's capability of
      reconstructing spatio-temporal activities of neural sources.

PMID- 11442289
TI  - Estimation of the VA/(Q+VTIS) distribution from single-breath alkane uptake.
AB  - In this paper, it was investigated if the ventilation-perfusion distribution can
      be estimated from the uptake (U) of inert gases with different solubilities
      during the single-breath maneuver. A model was implemented that describes U as a
      function of solubility for inhomogeneously distributed alveolar volume (VA)
      versus blood and tissue volume (Q + VTIS). The VA/(Q + VTIS) distribution
      describes the relative contribution of gas-exchange units with different VA/(Q +
      VTIS) ratios to the expiratory volume. U was derived as the sum of uptakes
      corresponding to different modes in the distribution, weighted with the relative
      contribution to the expiratory volume. This permits an estimation of the
      distribution parameters by fitting U as a function of solubility. The n alkanes
      were used because of their different solubilities. Analysis of the sensitivity of
      the estimated VA/(Q + VTIS) distribution parameters to measurement errors showed
      that mostly two modes can be discerned. The influence of fixed model parameters
      appeared relatively small. The model could well explain U in normal and
      emphysematous subjects, with a larger contribution of high VA/(Q + VTIS) ratios
      in the emphysematous subjects. It was concluded that the VA/(Q + VTIS)
      distribution can be estimated noninvasively from single-breath alkane uptake.

PMID- 11442290
TI  - Neuro-fuzzy extraction of angular information from muscle afferents for ankle
      control during standing in paraplegic subjects: an animal model.
AB  - This paper is part of a project whose aim is the implementation of closed-loop
      control of ankle angular position during functional electrical stimulation (FES)
      assisted standing in paraplegic subjects using natural sensory information. In
      this paper, a neural fuzzy (NF) model is implemented to extract angular position
      information from the electroneurographic signals recorded from muscle afferents
      using cuff electrodes in an animal model. The NF model, named dynamic
      nonsingleton fuzzy logic system is a Mamdani-like fuzzy system, implemented in
      the framework of recurrent neural networks. The fuzzification procedure
      implemented was the nonsingleton technique which has been shown in previous works
      to be able to take into account the uncertainty in the data. The proposed
      algorithm was tested in different situations and was able to predict reasonably
      well the ankle angular trajectories especially for small excursions (as during
      standing) and when the stimulation sites are far from the registration sites.
      This suggests it may be possible to use activity from muscle afferents recorded
      with cuff electrodes for FES closed-loop control of ankle position during quite
      standing.

PMID- 11442291
TI  - Artifact-resistant power-efficient design of finger-ring plethysmographic
      sensors.
AB  - A miniaturized, telemetric, photoplethysmograph (PPG) sensor for long-term,
      continuous monitoring is presented in this paper. The sensor, called a "ring
      sensor," is attached to a finger base for monitoring beat-to-beat pulsation, and
      the data is sent to a host computer via a radio-frequency transmitter. Two major
      design issues are addressed: one is to minimize motion artifact and the other is
      to minimize the consumption of battery power. An efficient double ring design is
      developed to lower the influence of external force, acceleration, and ambient
      light, and to hold the sensor gently and securely on the skin, so that the
      circulation at the finger may not be obstructed. Total power consumption is
      analyzed in relation to characteristics of individual components, sampling rate,
      and CPU clock speed. Optimal operating conditions are obtained for minimizing the
      power budget. A prototype ring sensor is designed and built based on the power
      budget analysis and the artifact-resistive attachment method. It is verified
      through experiments that the ring sensor is resistant to interfering forces and
      acceleration acting on the ring body. Benchmarking tests with FDA-approved PPG
      and electrocardiogram reveal that the ring sensor is comparable to those devices
      in detecting beat-to-beat pulsation despite disturbances.

PMID- 11442292
TI  - High-speed solution switching using piezo-based micropositioning stages.
AB  - Motion-induced vibration is a critical limitation in high-speed micropositioning
      stages used to achieve solution switching. Controlled rapid solution switching is
      used to study the fast activation and deactivation kinetics of ligand-gated ion
      channel populations isolated in excised membrane patches--such studies are needed
      to understand fundamental mechanisms that mediate synaptic excitation and
      inhibition in the central nervous system. However, as the solution-switching
      speed is increased, vibration induced in the piezo-based positioning stages can
      result in undesired, repeated, ligand application to the excised patch. The
      article describes a method to use knowledge of the piezo-stage's vibrational
      dynamics to compensate for and reduce these unwanted vibrations. The method was
      experimentally verified using an open-electrode technique, and fast solution
      switching (100 micros range) was achieved.

PMID- 11442293
TI  - In-shoe multisensory data acquisition system.
AB  - Patients with diabetes and peripheral neuropathy are susceptible to unnoticed
      trauma on the foot that can cause skin breakdown. We have designed an electronic
      system in a shoe that monitors temperature, pressure, and humidity, storing the
      data in a battery-powered device for later uploading to a host computer for data
      analysis. The pressure sensors are located at the heel, and under three
      metatarsal heads. Temperature sensors are located under the medial metatarsal
      head and under the heel. The humidity sensor is located in the toe of the shoe.
      Correlations of data from pressure sensors with known values were high (r >
      0.85), even after extended use. Although data currently are being collected for
      descriptive purposes, the design potentially can be used to provide feedback to
      patients.

PMID- 11442294
TI  - Computer-aided dynamic simulation of microwave-induced thermal distribution in
      coagulation of liver cancer.
AB  - To develop a method of dynamic three-dimensional (3-D) simulation of thermal
      distribution in ultrasound-guided microwave coagulation therapy of liver cancer
      and to verify its accuracy. The specific absorption rate (SAR) values were
      established by measuring the temperature in equivalent phantom tests. Those
      values were different under different power output condition. Dynamic 3-D
      temperature distributions were reconstructed with a finite-element model. Testing
      and rectification were performed through animal experiments and clinical trials,
      respectively. The temperature curves in the experiments corresponded well with
      simulated ones in vitro--91.4% and 88.9% using single and double electrodes,
      respectively. The measured coagulated boundary and simulated temperature boundary
      had a good correspondence in 85.7% of the specimens. In both in vivo experiments
      and clinical trials, blood perfusion influenced the rise in temperature
      significantly. Temperature curves between the simulations and actual measured
      results showed good correspondence--67.8% (19/28) in the patients with
      hepatocellular carcinoma. Distance between electrodes and combined thermal
      distributions were both optimized with computer-aided simulation during
      simultaneous two-electrode coagulation. The results demonstrated that computer
      aided simulation of microwave thermal distribution is an accurate and reliable
      method which provides a theoretical and technical basis for controlling
      coagulated tissue volume and placement of the electrodes during microwave
      coagulation therapy of liver cancer.

PMID- 11442295
TI  - An implantable power supply with an optically rechargeable lithium battery.
AB  - A novel power supply for medical implants has been developed. A wireless near
      infrared power transmission recharges a lithium secondary battery in the power
      supply. A photovoltaic cell array embedded under skin receives near-infrared
      light through the skin and charges the battery directly powering an implanted
      device. We have shown that, for a photodiode area of 2.1 cm2, 17 min of near
      infrared irradiation at a 810-nm wavelength with a power density of 22 mW/cm2 can
      send enough energy to allow regular commercial cardiac pacemakers to run for 24
      h. The temperature rise of the skin during the light irradiation was 1.4 degrees
      C.

PMID- 11442296
TI  - Measurement of functional residual capacity through the transient phase of He
      dilution in newborns.
AB  - Helium dilution maneuver is used to determine the functional residual capacity
      (FRC) 14 newborns ages 1-5 mo. The model equation describes the changing alveolar
      fractions of He and the ventilation promoted by a rebreathing procedure that does
      not exceed 40 s. The model does not involve the volume of the rebreathing bag
      usually needed when applying rebreathing technique and which is a source of
      error. The equation is discretized and solved for recorded data obtained with
      equipment adapted to newborns. Results show a strong relationship between FRC and
      the biometrical indexes, and confirm those found in the literature featuring that
      the measurement duration of FRC can be considerably shortened.

PMID- 11442297
TI  - Aligned microcontact printing of biomolecules on microelectronic device surfaces.
AB  - Microcontact printing (muCP) of extracellular matrix proteins is a fascinating
      approach to control cell positioning and outgrowth, which is essential in the
      development of applications ranging from cellular biosensors to tissue
      engineering. Microelectronic devices can be used to detect the activity from a
      large number of recording sites over the long term. However, signals from cells
      can only be recorded at small sensitive spots. In this paper, we present an
      innovative setup to perform aligned muCP of extracellular matrix proteins on
      microelectronic devices in order to guide the growth of electrogenic cells
      specifically to these sensitive spots. Our system is based on the combination of
      a fine-placer with redesigned micro stamps having a rigid glass cylinder as
      backbone for attachment in the alignment tool. Alignment is performed moving the
      device with an optical table under microscopic control of the superimposed images
      from stamp and device surface. After successful alignment, the stamp is brought
      into contact with the device surface by means of a high-precision lever. With our
      setup, we were able to pattern up to 40 devices per hour. A lateral alignment
      accuracy of < 2microm has been achieved. Aligned neuronal growth on patterned
      devices was demonstrated with dissociated hippocampal neurons.

PMID- 11442298
TI  - Alzheimer's disease: insights from epidemiology.
AB  - While a complete understanding of the pathogenesis of Alzheimer's disease (AD)
      remains elusive, many conclusions can be drawn from the numerous epidemiological
      studies undertaken to date. Prevalence and incidence estimates show consistency,
      following a roughly exponential pattern with a doubling of both parameters
      roughly every five years after age 65. Roughly 7% of the population aged 65 and
      over has AD. The clinical course of the disease is reasonably well established
      and mortality rates rise with increasing levels of cognitive deficit. Four risk
      factors for AD are firmly established: increasing age, the presence of the
      apolipoproteinE-epsilon4 allele, familial aggregation of cases, and Down's
      syndrome. Numerous other associations have been shown in some studies, but not in
      others. For example, women generally appear at higher risk than men, as do people
      with lower levels of education; depression is probably prodromal; head injury is
      an established risk factor, and may interact with the apoE gene; several
      occupational exposures appear hazardous, and exposure to aluminum in the water
      supply confers excess risk. Hypertension and other vascular symptoms appear to
      predispose to AD, which is now seen as nosologically closer to vascular dementia
      than was previously believed. Several apparently protective factors have been
      identified, although preventive trials based on these have so far shown minimal
      effectiveness. The use of non-steroidal anti-inflammatory drugs to treat
      arthritis is associated with a reduced risk of AD, as is estrogen use by post
      menopausal women. Physical activity appears beneficial, as does a diet with high
      levels of vitamins B6, B12 and folate. while red wine in moderate quantities
      appears protective. This review concludes with a discussion of the strengths and
      limitations of current epidemiological methods for studying Alzheimer's disease.

PMID- 11442299
TI  - Neuroinflammation and the genetics of Alzheimer's disease: the search for a pro
      inflammatory phenotype.
AB  - The role of interleukin 1 (IL-1) and interleukin 6 (IL-6) in the pathogenesis of
      Alzheimer's disease (AD) is reviewed within the framework of "inflamm-aging",
      i.e., the characteristic chronic pro-inflammatory status which develops in old
      age, and neuroinflammation, i.e., the peculiar inflammatory process which is
      present in the brain of AD patients. In particular, the data suggesting that
      several IL-1 and IL-6 gene polymorphisms can contribute to the risk of developing
      AD are reviewed. The possibility as well as the difficulty in identifying a pro
      inflammatory phenotype, and its importance for the prevention, diagnosis and
      therapy of AD and other age-related pathologies are discussed.

PMID- 11442300
TI  - Natural history of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the principal cause of dementia in the elderly, and
      affects about 15 million people worldwide. The earliest symptom is usually an
      insidious impairment of memory. As the disease progresses, there is increasing
      impairment of language and other cognitive functions. Problems occur with naming
      and word-finding, and later with verbal and written comprehension and expression.
      Visuospatial, analytic and abstract reasoning abilities, judgment, and insight
      become affected. Behavioral changes may include delusions, hallucinations,
      irritability, agitation, verbal or physical aggression, wandering, and
      disinhibition. Ultimately, there is loss of self-hygiene, eating, dressing, and
      ambulatory abilities, and incontinence and motor dysfunction. Before diagnosis of
      AD, individuals may have memory complaints, which represent a period of mild
      cognitive impairment (MCI). Before MCI, there is a prodromal, ill-defined
      presymptomatic period of disease ('pre-MCI"). In this review, we particularly
      focus on these earliest stages. We also discuss the more advanced stages of AD,
      and address factors that may influence disease course. Understanding the natural
      history of AD will allow better targeting of the disease-modifying treatments
      that are on the horizon.

PMID- 11442301
TI  - Mild cognitive impairment: clinical features and review of screening instruments.
AB  - Clinical criteria to recognize subjects with cognitive impairment in the pre
      dementia stage are becoming available. These are frail subjects, at risk of
      adverse outcomes, such as death, institutionalization, and functional and
      cognitive deterioration. Early identification of these subjects has a great
      importance in order to start rehabilitative or pharmacological interventions that
      could slow the progression of cognitive impairment, and the onset of disability.
      In this regard, cognitive screening tests might be helpful in different clinical
      settings (general practice, acute care, rehabilitation, and nursing home). We
      describe the most frequent clinical presentations of cognitive impairment in the
      pre-dementia stage, and review eleven screening tests to provide recommendations
      on which should be preferred in each setting.

PMID- 11442302
TI  - Structural neuroimaging of Alzheimer's disease and other dementias.
AB  - This paper reviews the use of imaging techniques to aid in the clinical diagnosis
      of dementia. Two approaches are distinguished. One is the exclusionary approach
      in which imaging is used to rule out diseases that would mimic or cause dementia;
      based on the literature, this approach yields very little, if any, information
      that was not identified clinically. The more positive approach uses imaging as a
      diagnostic tool to identify changes specific for causes of dementia; any
      assessment of medial temporal lobe atrophy on Magnetic Resonance Imaging (MRI)
      will result in a reasonably high positive likelihood ratio distinguishing AD
      patients from non-demented individuals, but fails to distinguish AD patients from
      patients with other dementias. For a diagnosis of vascular dementia imaging is
      necessary, although not all vascular changes fulfill requirements of being
      relevant to dementia. Potentially of more importance, given the higher prevalence
      of AD, is the identification of concomitant vascular changes in AD that may be
      amenable to therapy, and may be used to identify subgroups. Structural and
      functional MRI techniques have great potential in identifying patients at risk
      for AD, which will allow for a very early treatment with drugs that slow or even
      halt progression.

PMID- 11442303
TI  - Neuropsychological tests in Alzheimer's disease.
AB  - The recent development of symptomatic pharmacological treatment for Alzheimer's
      disease (AD) and the probable introduction of new therapies in a near future make
      the assessment of dementia at its different stages an even greater scientific and
      public health challenge. Neuropsychological tests, together with clinical data,
      are at present the only in vivo non-invasive screening and diagnostic tools for
      AD and related disorders. This chapter reviews the application to AD of standard
      batteries and short screening tests. It also analyzes the tests to be applied to
      detect and assess the specific deficits of the disease, and discusses the
      advantages and flaws of current screening and diagnostic tests of dementia.
      Emphasis is placed on the need to devise and use tests developed in a rational
      manner, with high sensitivity and specificity, not only in the moderate stages of
      the disease, but also in the very early and even "preclinical" stages, as well as
      during the late stages (severe dementia). It is known that neuropsychological
      tests allow one to determine various patients' profiles. Future research should
      determine the possible predictive value of these profiles. This has important
      implications for therapeutic trials. The current implicit assumption that all
      patients with AD tend to evolve and decline in a similar fashion needs to be
      critically re-examined.

PMID- 11442304
TI  - Clinical aspects of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common of the dementing disorders. AD begins
      insidiously and progresses gradually; it is characterized clinically not only by
      an impairment in cognition, but also by a decline in global function, a
      deterioration in the ability to perform activities of daily living, and the
      appearance of behavioral disturbances. No definitive tests for the diagnosis are
      available, and AD is a diagnosis of inclusion based on patient history, physical
      examination, neuropsychological testing, and laboratory studies. Disease
      progression is highly variable, and median survival after the onset of dementia
      ranges from 5 to 9.3 years. Early recognition of AD allows time to plan for the
      future, and to treat patients before marked deterioration occurs.

PMID- 11442305
TI  - Heart disease and vascular risk factors in the cognitively impaired elderly:
      implications for Alzheimer's dementia.
AB  - The term "cardiogenic dementia" was introduced a few decades ago to indicate an
      alteration of consciousness and cognition due to heart disease. Although this
      term is now disused, the relationship between cardiovascular disease and
      cognitive impairment is currently of great interest, not only for its potential
      therapeutic implications. but also for the recently recognized important role
      that vascular factors appear to play in Alzheimer's disease. The aims of this
      review are therefore 1) to show data supporting the role of cardiac disease-
      namely congestive heart failure, myocardial infarction and atrial fibrillation-
      and other vascular risk factors--i.e., hypertension and diabetes--in the
      development or worsening of cognitive impairment; 2) to highlight recent
      observations on the relationship between presence and severity of congestive
      heart failure/ myocardial infarction/atrial fibrillation and Alzheimer's disease:
      and 3) to uncover the type of studies needed in this field in order to facilitate
      a more precise algorithm of dementia prevention as well as intervention in
      demented patients with cardiovascular disease.

PMID- 11442306
TI  - Is anti-cholinesterase therapy of Alzheimer's disease delaying progression?
AB  - During the last decade, a systematic effort to develop a pharmacological
      treatment for Alzheimer's disease (AD) resulted in three drugs being registered
      for the first time in the US and Europe. All three compounds are cholinesterase
      inhibitors (ChEI). The major therapeutic effect of ChEI on AD patients is to
      maintain cognitive function at a stable level during a 6-month to 1-year period
      of treatment, as compared to placebo. Additional drug effects are to slow down
      cognitive deterioration and improve behavioral and daily living activity. Recent
      studies show that in many patients the cognitive stabilization effect can be
      prolonged up to 24 months. This long-lasting effect suggests a mechanism of
      action other than symptomatic, and directly cholinergic. In vitro and in vivo
      studies have consistently demonstrated a link between cholinergic activation and
      amyloid precursor protein (APP) metabolism. Lesions of cholinergic nuclei cause a
      rapid increase in cortical APP and cholinergic synaptic function; the effect of
      such lesions can be reversed by ChEI treatment. A reduction in cholinergic
      neurotransmission, experimental or pathological, leads to amyloidogenic
      metabolism and contributes to the development of neuropathology and cognitive
      dysfunction. To explain the long-term effect of ChEI, for which evidence is
      available on an experimental as well as clinical level, a mechanism based on beta
      amyloid metabolism is postulated. The question whether cholinergic stabilization
      implies simply slowing down progression of disability or also involves delay of
      disease progression is discussed.

PMID- 11442307
TI  - Economic considerations of Alzheimer's disease and related disorders.
AB  - Economic analyses of geriatric syndromes are seldom performed. However,
      demographic and epidemiological imperatives have led to significant interest in
      the evaluation of AD-related costs. Over 300 papers devoted to economic
      considerations of Alzheimer's disease have been published in peer-reviewed
      journals, within the last five years. In these papers, the chosen perspective
      (costs to society or to specific payers) is important. Analytical methods are
      still evolving and remain complex. Unresolved methodological issues will need to
      be addressed to further our understanding of long-term economic consequences. At
      present, it is clear that diagnostic and drug costs are low compared to the major
      cost of institutionalization. Thus, directing efforts at early diagnosis and
      delaying nursing home placement are two key cost-containment interventions. In
      this respect, the need to support informal care should not be underestimated.

PMID- 11442308
TI  - Sepsis research: what did we do wrong? What would Semmelweis do today?

PMID- 11442309
TI  - Injury-enhanced calcium mobilization in circulating rat neutrophils models human
      PMN responses.
AB  - G-protein coupled (GPC) chemoattractants are important neutrophil (PMN)
      activators in human shock and sepsis, acting in part by increasing cytosolic
      calcium ([Ca2+]i). Rats are widely used as laboratory models of shock and sepsis,
      but reports of [Ca2+]i flux in circulating rat PMN are rare. Moreover, the
      [Ca2+]i values reported often differ markedly from human systems. We developed
      study methods where basal [Ca2+]i values in circulating rat PMN were comparable
      to human PMN, but rat PMN still mobilized calcium poorly after stimulation.
      Trauma (laparotomy) did not change rat PMN basal [Ca2+]i, but induced brisk
      [Ca2+]i responses to chemokine and lipid mediators that approximated human PMN
      responses. This was associated with marked loading of microsomal calcium stores.
      Formyl peptides still mobilized calcium less well in rat than human PMN. Normal
      rat PMN appear to circulate in a less mature or primed form than human PMN. A
      very limited injury rapidly converts rat PMN to a more activated phenotype. PMN
      thus activated act quite similar to human PMN in terms of GPC receptor-mediated
      calcium mobilization. Trauma enhances rat PMN responses to GPC agonists at least
      in part by loading cell calcium stores.

PMID- 11442310
TI  - Mast cells mediate complement activation after acid aspiration.
AB  - A significant role for the alternative complement pathway in acid aspiration has
      been demonstrated by the observation that C3 but not C4 genetic knockout mice are
      protected from permeability edema. Using mast cell-deficient mice (W/Wv), we
      tested the hypothesis that mast cells mediate complement activation after acid
      aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mL/kg 0.1 N
      HCL was instilled in the trachea. After 4 h, extravasation of 125I-albumin was
      used to calculate lung vascular permeability. The serum alternative complement
      pathway hemolytic activity was examined, and lung immunohistochemistry was
      performed. Lung permeability in W/Wv mice was 62% less than that of mast cell
      sufficient (+/+) animals and similar to +/+ mice treated with the chymase
      inhibitor chymostatin (65% decrease). Treatment of +/+ mice with D-PRO2,D
      TRP(7,9)-Substance P, an antagonist to the neuropeptide substance P, reduced
      injury by 66%. Serum complement hemolytic activity was intact in injured w/wv
      mice and +/+ animals treated with chymostatin or dpdt-sp, but was decreased to
      65% in the injured untreated +/+ group. Alveolar C3 deposition was intense in
      injured untreated +/+ mice but absent in the other groups. We interpret these
      data to indicate that mast cells mediate complement activation, via chymase
      degranulation, after acid aspiration. This mast cell activity likely is regulated
      by the release of substance P.

PMID- 11442311
TI  - Possible role of TNF on procalcitonin release in a baboon model of sepsis.
AB  - Procalcitonin (PCT) has been described as an early and discriminating marker of
      bacteria-associated sepsis in patients. However, little is known of its source
      and actions, especially with regard to its relation to tumor necrosis factor
      (TNF). TNF is responsible for the release of several other mediators of sepsis
      e.g., chemokines. We tested the hypothesis that plasma PCT levels during sepsis
      differ with regard to the degree of TNF availability. Severe hyperdynamic sepsis
      was induced in baboons (n = 14) by i.v. infusion of live E. coli (approximately 2
      x 10(9) colony-forming units/kg) over 2 h. Animals were pretreated 2 h before E.
      coli either with 1 mg/kg humanized anti-TNF antibody (CDP571) or placebo (Ringer
      solution). Plasma PCT levels at baseline was barely detectable, but increased to
      about 4000 pg/mL at 4 h after E. coli infusion. Levels were maximal between 8 and
      24 h and had returned nearly to baseline at 72 h. Although no TNF could be
      measured in the treated group, PCT levels were not different between the placebo
      and the TNF antibody treatment group. We conclude that PCT levels are not
      dependent on the systemic presence of TNF in an E. coli sepsis model in baboons.
      Such sepsis induced PCT release is clearly different from the previously reported
      PCT release during infusion of rhTNF in volunteers or chimpanzees.

PMID- 11442312
TI  - Gut luminal endotoxin reduces ischemia-reperfusion injury of the small gut in
      germ-free pigs.
AB  - Translocation of luminal bacteria and their products through the intestinal
      mucosa during ischemia-reperfusion (I/R) may modify I/R injury. To test this
      hypothesis, 16 germ-free pigs were studied prior to and after clamping the
      superior mesenteric artery (SMA) and 12 pigs served as controls. Nine pigs in the
      I/R and 5 in the control group received endotoxin intragastrically, 60 min before
      baseline. Gut absorption of an inert indicator (polyethyleneglycol [PEG] 3350),
      gut intraluminal PCO2 (tonometry), and systemic and regional hemodynamic
      variables were measured up to 4 h after baseline. Gut blood flow was stopped
      during clamping, some reactive hyperemia occurred up to 30 min after declamping
      in the I/R groups, independently of prior endotoxin administration. Gut
      intraluminal-arterial PCO2 gradients were elevated in I/R versus control groups
      during I and for some time during R, prior endotoxin had no effect. However, in
      controls without and with luminal endotoxin, PEG urinary excretion, as percentage
      of the dose administered, was 0.12 +/- 0.12 and 0.17 +/- 0.07, respectively,
      while it measured 1.82 +/- 0.70 in the I/R group and 0.55 +/- 0.37% in the I/R
      and endotoxin groups, respectively (P< 0.001). The data suggest that gut luminal
      endotoxin ameliorates I/R injury of the gut wall in germ-free pigs, without
      altering changes in gut perfusion adequacy and systemic hemodynamics.

PMID- 11442313
TI  - Impairment of the ryanodine-sensitive calcium release channels in the cardiac
      sarcoplasmic reticulum and its underlying mechanism during the hypodynamic phase
      of sepsis.
AB  - Changes in Ca2+-induced Ca2+ release in cardiac sarcoplasmic reticulum (SR)
      during different phases of sepsis were studied. Sepsis was induced by cecal
      ligation and puncture (CLP). The 45Ca2+ release studies show that the amount of
      Ca2+ released from the passively and the actively loaded SR vesicles was
      unaffected during the early sepsis (9 h after CLP), but it was significantly
      decreased during the late phase (18 h after CLP) of sepsis. The [3H]ryanodine
      binding assays reveal that the Bmax for ryanodine binding was unaffected during
      the early phase, but was decreased by 32.1% during the late phase of sepsis. The
      affinity of ryanodine receptor for Ca2+ remained unchanged during sepsis. ATP,
      AMP-PCP, and caffeine stimulated binding, while MgCl2 and ruthenium red inhibited
      [3H]ryanodine binding in control, early sepsis, and late sepsis groups. The EC50
      and IC50 values for these regulators were unaffected during the progression of
      sepsis. Digestion of control SR with phospholipase A2 decreased [3H]ryanodine
      binding and the decrease was reversible by the addition of phosphatidylcholine
      (PC), phosphatidylethanolamine (PE), or phosphatidylserine (PS). Addition of PC,
      PE, or PS to the SR isolated from septic rats stimulated [3H]ryanodine binding.
      These data demonstrate that Ca2+-induced Ca2+ release from cardiac SR remained
      relatively unaffected during the early phase, but was significantly impaired
      during the late phase of sepsis. The sepsis-induced impairment in SR Ca2+ release
      is a result of a quantitative reduction in the number of Ca2+ release channels.
      Furthermore, the reduction is associated with a mechanism involving a
      modification of membrane lipid profile in response to certain stimuli such as
      activation of phospholipase A2.

PMID- 11442314
TI  - Progressive decrease in constrictor reactivity of the non-absorbing intestine
      during chronic sepsis.
AB  - Chronic sepsis leads to an impaired intestinal microcirculation, which might
      reflect altered microvascular control. We hypothesized that intestinal
      microvascular sensitivity to norepinephrine (NE) is decreased during chronic
      sepsis. Chronic sepsis was induced by a polymicrobial inoculation of implanted
      subcutaneous sponges in rats. Septic rats were studied either 24 or 72 h after a
      single inoculation (1-hit) of bacteria. Other rats received a second inoculation
      (2-hit) of bacteria 48 h later and were studied at 24 h after the second
      inoculation. NE (0.01-1.0 microM) responses in the non-absorbing terminal ileal
      arterioles (inflow A1, proximal-p and distal-d premucosal A3) were measured by
      video microscopy. NE threshold sensitivity (pD(T20) = -log of 20% response dose)
      was analyzed. pD(T20) was significantly decreased in A1, pA3, and dA3 of 1-hit 24
      h septic rats (P < 0.05), and was further decreased in all vessels of 2-hit 72-h
      septic rats (P < 0.05). In contrast, the pDT(T20) of all three vessels
      significantly returned toward normal values after 72 h in rats that had only 1
      bacteria inoculation. We conclude that an initial bacterial challenge decreases
      vasoconstrictor reactivity of the intestinal microcirculation and that subsequent
      repeated bacterial challenge exacerbates this defect in vasoconstrictor control
      in the non-absorbing intestine.

PMID- 11442315
TI  - Hypercholesterolemia alters endotoxin-induced endothelial cell adhesion molecule
      expression.
AB  - While there is a growing body of evidence suggesting that hypercholesterolemia
      prior to the onset of atherosclerosis renders tissues more susceptible to
      inflammation, the mechanisms that underlie this exaggerated inflammatory response
      remain poorly defined. The overall objective of this study was to assess the
      influence of hypercholesterolemia on endotoxin-induced endothelial cell adhesion
      molecule (CAM) expression in different vascular beds. Another objective was to
      determine whether the altered endothelial CAM expression in hypercholesterolemic
      animals is associated with a corresponding change in plasma cytokine levels. Male
      Sprague/Dawley rats (SD) were placed either on a normal (control) or high
      cholesterol (HC) diet for 3 weeks. The dual radiolabeled monoclonal antibody
      (mAb) technique was used to measure the expression of P-selectin, E-selectin,
      ICAM-1, and VCAM-1 in different vascular beds after intraperitoneal injection of
      endotoxin (LPS) derived from Salmonella abortus equi. LPS induced a significant
      increase in the expression of all endothelial CAMs in both normocholesterolemic
      and hypercholesterolemic groups. However, hypercholesterolemia enhanced LPS
      induced expression of P-selectin, E-selectin, and ICAM-1 in several vascular
      beds, while VCAM-1 expression was unaffected. Thrombocytopenia, induced with anti
      platelet serum, did not alter LPS-induced P-selectin expression in either group,
      suggesting that platelets do not contribute to this response.
      Hypercholesterolemia was associated with an exaggerated increase in plasma TNF
      alpha, but not IL-1beta, after LPS treatment. These results indicate that
      hypercholesterolemia in rats may render tissues more vulnerable to the
      inflammatory effects of LPS by enhancing the expression of certain endothelial
      CAMs.

PMID- 11442316
TI  - Inducible nitric oxide synthase knockout mice exhibit resistance to the multiple
      organ failure induced by zymosan.
AB  - In the present study, by comparing the responses in wild-type mice (+/+) and mice
      lacking (-/-) the inducible (or type 2) nitric oxide synthase (iNOS), we
      investigated the role played by iNOS in the development of non-septic shock. A
      severe inflammatory response characterized by peritoneal exudation, high
      peritoneal levels of nitrate/nitrite, and leukocyte infiltration into peritoneal
      exudate was induced by zymosan administration in iNOS +/+ mice. This inflammatory
      process coincided with the damage of lung, liver, and small intestine, as
      assessed by histological examination. Lung, small intestine, and liver
      myeloperoxidase (MPO) activity, indicative of neutrophil infiltration and lipid
      peroxidation, were significantly increased in zymosan-treated iNOS +/+ mice.
      Peritoneal administration of zymosan in the iNOS +/+ mice induced also a
      significant increase in the plasma levels of nitrite/nitrate and in the levels of
      peroxynitrite at 18 h after zymosan challenge. Immunohistochemical examination
      demonstrated a marked increase in the immunoreactivity to nitrotyrosine and to
      poly ADP-ribose synthetase (PARS) in the lung, liver, and intestine of zymosan
      treated iNOS +/+ mice. The intensity and degree of nitrotyrosine and PARS were
      markedly reduced in tissue section from zymosan-iNOS -/- mice. Zymosan-treated
      iNOS -/- mice showed a significantly decreased mortality and inhibition of the
      development of peritonitis. In addition, iNOS -/- mice showed a significant
      protection on the development of organ failure since tissue injury and MPO were
      reduced in lung, small intestine, and liver. Furthermore, a significant reduction
      of suppression of mitochondrial respiration, DNA strand breakage, and reduction
      of cellular levels of NAD+ was observed in ex vivo macrophages harvested from the
      peritoneal cavity of iNOS -/- mice subjected to zymosan-induced non-septic shock.
      In vivo treatment with aminoguanidine (300 mg/kg 1 and 6 h after zymosan
      administration) significantly prevents the inflammatory process. Taken together,
      our results clearly demonstrate that iNOS plays an important role in zymosan
      induced non-septic shock.

PMID- 11442317
TI  - The role of bacterial translocation on neutrophil activation during hemorrhagic
      shock in rats.
AB  - Some biological responses to hemorrhage have been reported to be associated with
      bacterial translocation (BT). While the relationship between peripheral blood
      neutrophils and BT in the late phase of hemorrhagic shock or burn injury has been
      reported, this relationship in the early phase has not been fully elucidated. We
      investigate the role of BT in neutrophil activation and priming during
      hemorrhagic shock. The experimental rats were divided into three groups: a group
      with normal intestinal flora (NF group), an antibiotic-decontaminated group (AD
      group), and a sham shock group with normal intestinal flora (sham group).
      Hemorrhagic shock was induced in the NF and AD groups (MAP 30 mm Hg for 30-90
      min). The rats were sacrificed at 30, 60, or 90 min following the shock
      induction. Cultures were taken from the liver, spleen, mesenteric lymph nodes
      (MLNs), and systemic blood to assess the occurrence of BT. Hydrogen peroxide
      generation and CD11b/c expression were assayed by flow cytometry to evaluate
      peripheral blood neutrophil activation and priming, respectively. In the NF
      group, significant BT to the MLNs and spleen was noted from 30 min after the
      shock induction, and significant hydrogen peroxide generation was also noted from
      30 min. The expression of CD11b/c on neutrophils was significantly up-regulated
      at 90 min after the shock induction. Furthermore, BT, as also the aforementioned
      parameters of neutrophil function, was significantly suppressed in the AD group.
      We, therefore, concluded that neutrophil activation and priming during
      hemorrhagic shock might be closely related to BT, and that infectious factors
      possibly influence the host responses starting from the early phase of damage,
      even in noninfectious stress-inducing conditions.

PMID- 11442318
TI  - Calcitonin gene-related peptide-enhanced nitric oxide release and inducible NOS
      activity and mRNA expression in LPS-stimulated mouse peritoneal macrophages.
AB  - Previously we have shown that calcitonin gene-related peptide (CGRP), a
      neuropeptide increases lipopolysaccharide- (LPS) induced nitric oxide (NO)
      production in mouse peritoneal macrophages by using the Griess method. In this
      study we further examined whether CGRP could modulate inducible NO synthase
      (iNOS) protein and mRNA expression from mouse peritoneal macrophages. Macrophages
      were obtained from the peritoneal exude of male Balb/c mouse. The cells were
      plated on culture dishes at a density of 5 x 10(5) cells per well and were
      allowed to adhere for 2 h. After incubation for 24 h, the macrophages were
      cultured with 0.01 to 1 microg/mL LPS with or without CGRP (1-1,000 nM) for 24 h.
      The results showed that CGRP markedly enhanced 0.5 microg/mL LPS-induced NO
      release as compared with that of lower doses of LPS, such as 0.01 and 0.1
      microg/mL LPS. NO was increased from 19.8 +/- 2.6 to the highest level of 31.5 +/
      4.2 microM in 5 x 10(5) cells by 10 nM CGRP in 0.5 microg/mL LPS-stimulated
      macrophages. The cGMP level in macrophages was augmented when CGRP was added with
      LPS. However, when using higher dose (1.0 microg/mL) of LPS to stimulate the
      macrophages, CGRP had no effect at all on NO release. CGRP had no direct effect
      on NO and cGMP production. CGRP increased the expression of inducible NOS protein
      in LPS-stimulated macrophages shown by immunocytochemistry method. The activity
      of iNOS was also enhanced by CGRP as compared with LPS-stimulation alone by
      detecting the 3H-L-citruline formation from 3H-L-arginine. We found that CGRP
      also increased the LPS-induced iNOS mRNA levels by using reverse transcriptase
      PCR method. These data suggest that CGRP enhances LPS-induced NO release, iNOS
      activity, and iNOS mRNA in mouse peritoneal macrophages.

PMID- 11442319
TI  - Treatment of hyperthermia-induced extravasation with hypertonic saline (7.5%) in
      6% dextran 70 (HSD) in Wistar/Furth rats.
AB  - This study determined the effectiveness of hypertonic saline (7.5%) in 6% Dextran
      70 (HSD) in reducing hyperthermia-induced extravasation in Wistar/Furth (WF) rats
      and compared this extravasation with that previously reported in Sprague-Dawley
      (SD) rats. Wistar/Furth rats (male, n = 12/group, 300-325 g) were placed
      unrestrained in a chamber (41.5 degrees C) until a core temperature (Tc) of 42.6
      degrees C was attained. Immediately following heat exposure, HSD or normal saline
      (4 mL/kg) was administered via jugular catheter, followed 15 min later by Evan's
      blue (Eb, 25 mg/kg) in normal saline. After another 15-min interval, animals were
      anesthetized, exsanguinated, tissues removed and washed in normal saline, and Eb
      was extracted with formamide. Another group of normothermic WF rats were also
      given Eb and had tissues harvested. Comparisons were made to extravasation in
      normothermic and hyperthermic SD rats. In hyperthermic SD rats, Eb content
      increased significantly in liver, kidney, and intestinal tissues. In hyperthermic
      WF rats compared to normothermic WF rats, Eb content of kidney and spleen was
      increased; however, Eb content of heart, skeletal muscle, and intestine was
      significantly decreased. HSD-treated WF rats had increased extravasation in
      intestinal tissue compared to that of saline-treated rats. However, HSD treatment
      resulted in significant decreases in wet weight/dry weight ratios of heart (4.34
      +/- 0.10 versus 4.51 +/- 0.11) and skeletal muscle tissue (3.78 +/- 0.08 versus
      3.91 +/- 0.08). Findings of this study indicate that HSD did not prevent the
      hyperthermia-induced extravasation of Eb in kidney and spleen; that the increase
      in plasma volume following HSD administration is most likely due to the movement
      of fluid into the vasculature from the skeletal muscle mass; and that the WF
      strain may have limited value for the study of extravasation.

PMID- 11442320
TI  - Intra-hepatic expression of scavenger receptor and CD14 and their relationship
      with local inflammatory responses in endotoxemia in mice.
AB  - Our objective was to investigate the expression of scavenger receptor (SR) and
      CD14 in the liver and their relationship with local anti-inflammatory and
      proinflammatory responses in endotoxemia in order to uncover the mechanism for
      the liver to turn into effector organ from defense one at the level of cell
      receptors in sepsis. Mouse models of endotoxemia of different severity were
      reproduced by injection of different doses of lipopolysaccharide (LPS) via tail
      vein. Expression of SR and CD14 in the liver was assayed by immunohistochemistry
      and was then analyzed with an image analysis system. The levels of TNFalpha, IL
      6, IL-4, and IL-10 in liver tissue were determined with ELISA. Expression of SR
      in the liver in the high-dose group was markedly decreased 1 h after injection of
      LPS, and also in low- and medium-dose groups at 3 h. The expression of SR in the
      liver in the three groups was shown to be progressively decreased with the time
      prolonged. There was significant difference in average optical density (OD)
      values of SR among the three groups. The expression of CD14 in the liver in the
      three groups was shown to be significantly increased 1 h after injection of LPS,
      and much more with the time prolonged. But there was no significant difference in
      OD values of CD14 among the three groups. The contents of intrahepatic
      proinflammatory mediators TNFalpha and IL-6 and anti-inflammatory mediators IL-4
      and IL-10 were successively significantly increased after injection of LPS. The
      release of anti-inflammatory mediators was shown to be later than that of
      proinflammatory mediators. Correlation analysis indicated that there was negative
      correlation between expression of SR and CD14, and that changes of TNFalpha, IL
      6, IL-4, and IL-10 levels in liver tissues were correlated significantly
      positively with OD values of CD14 and negatively with OD values of SR. Expression
      of SR in the liver was shown to be progressively decreased, and that of CD14
      increased in endotoxemia, which was closely related to the uncontrolled
      inflammatory response in liver. This might be an important mechanism for the
      liver to turn into effector organ from defense one in sepsis.

PMID- 11442321
TI  - Plasma protein loss during surgery: beneficial effects of albumin substitution.
AB  - Plasma protein loss during abdominal surgery is a known phenomenon, but its
      possible pathophysiological relevance has remained unknown. The present study
      evaluates the effects of albumin substitution on systemic and local hemodynamics
      and cellular interactions in the mesenteric microcirculation. Rats underwent
      median laparotomy and exteriorization of an ileal loop for intravital microscopy
      of the mesenteric microcirculation. Plasma protein concentrations, systemic and
      local hemodynamics were recorded during the follow up period, with or without
      albumin substitution. Depending on the time course of plasma protein loss in
      control experiments, 80% of the calculated protein loss was infused during the
      first 2 h of surgery, and the other 20% over the following 5 h of intravital
      microscopy. The control group received a continuous infusion of normal saline.
      Plasma protein loss was mainly due to loss of albumin. A significant increase in
      adherent and rolling leukocytes was observed during the course of mesenteric
      exteriorization, which was almost entirely reversed by albumin replacement.
      Albumin substitution led to stabilisation of mean arterial pressure and abdominal
      blood flow and also attenuated reductions in arterial base excess. Albumin
      infusions to replace plasma protein loss may be a simple and effective measure to
      attenuate microcirculatory disturbances and may be of benefit in patients
      undergoing abdominal surgery.

PMID- 11442322
TI  - Amyotrophic lateral sclerosis: pathogenesis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by
      motor neuron degeneration. A subgroup of familial cases arises from mutations in
      the gene encoding cytosolic superoxide dismutase (SOD1). This review considers
      insight now being gained into ALS pathogenesis from the study of mutant SOD1
      protein and its possible mechanisms of adverse effect on nerve cells. Also
      discussed are the status of other genetic forms of ALS and the elusive question
      of why this disorder so specifically targets motor neurons. Ultimately, it is
      hoped that insights from these types of studies will improve the prospects for
      developing meaningful therapies of ALS.

PMID- 11442323
TI  - Clinical electrophysiology of the upper and lower motor neuron in amyotrophic
      lateral sclerosis.
AB  - Electrophysiology is important in amyotrophic lateral sclerosis (ALS). It helps
      in the assessment of disease severity and rate of progression, and it plays a
      role in evaluating the efficacy of therapeutic trials. Presently,
      electrophysiology is the only means of confirming suspected ALS, and this has
      been incorporated into the El Escorial criteria. Needle electromyography
      identifies disease in clinically "unaffected muscles" including bulbar
      musculature, confirms involvement of anterior horn cells, and can detect early
      involvement of respiratory muscles (intercostals and diaphragm). Conduction
      studies are imperative to rule out motor neuropathy with multifocal conduction
      block. Various techniques (cortical threshold, cortical silent period, double
      stimulation) employing transcranial magnetic stimulation have demonstrated that
      the motor cortex in ALS is hyperexcitable. Central motor conduction is normal in
      ALS but uniquely slow in the D9OA SOD1 mutation. Using peristimulus time
      histograms (PSTHs) it is possible to estimate the size of a unitary excitatory
      postsynaptic potential (EPSP). In ALS the EPSP is typically desynchronized. With
      time it becomes reduced in amplitude and a slow conducting component becomes
      recognizable in the primary peak of the PSTH. This reflects conduction through a
      slow motor pathway. Abnormalities of the PSTH are not seen in Kennedy's disease,
      implying that the changes seen in ALS are due to supraspinal mechanisms.

PMID- 11442324
TI  - Clinical characteristics and management of ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor
      neuron disease in adulthood. The clinical picture was accurately described by
      Charcot over 125 years ago and consists of generalized fasciculations,
      progressive atrophy and weakness of the skeletal muscles, spasticity and
      pyramidal tract signs, dysarthria, dysphagia, and dyspnea. Pseudobulbar affect is
      common. Disease-specific treatment options are still unsatisfactory. However,
      therapeutic nihilism is not justified as a large array of palliative measures is
      available to enhance the quality of life of patients and their families.
      Palliative care in ALS is a multidisciplinary effort requiring careful
      coordination. An open and frank disclosure of the diagnosis is of paramount
      importance. Nutritional deficiency due to pronounced dysphagia can be relieved by
      a percutaneous endoscopic gastrostomy. Respiratory insufficiency can be
      effectively treated by noninvasive home mechanical ventilation. The terminal
      phase of the disease should be discussed, at the latest, when symptoms of dyspnea
      appear in order to prevent unwarranted fears of "choking to death." Collaboration
      with hospice and completion of advance directives can be of invaluable help in
      the terminal phase.

PMID- 11442325
TI  - Clinical trials in ALS: an overview.
AB  - Clinical trials in amyotrophic lateral sclerosis (ALS) have been conducted for
      over half a century now and have incorporated a wide variety of drugs. Most of
      these trials have had negative results and a cure remains elusive. The explosion
      in our understanding of molecular biology and parallel developments in clinical
      epidemiology have opened up a vast number of novel therapeutic strategies.
      However, advances in statistical analysis, computing, and global communications
      have also put greater pressure on scientific investigators to improve the design
      and implementation of clinical trials so that they permit rigorous testing of
      hypotheses within a solid ethical framework. This article documents the first
      published trial for all drugs tried clinically in the treatment of ALS, focusing
      in more detail on the large, multicenter trials of recent years, namely those
      involving riluzole, ciliary neurotrophic factor, insulin-like growth factor-I,
      brain-derived neurotrophic factor, and SR57746A. The problems in the design of
      trials in ALS are discussed, including the selection of end points and surrogate
      markers of disease progression, and the major parameters in ALS assessment are
      reviewed.

PMID- 11442326
TI  - Atypical motor neuron disease and related motor syndromes.
AB  - There is an imperative need for the early diagnosis of amyotrophic lateral
      sclerosis/motor neuron disease (ALS/MND) in the current era of emerging
      treatments. When evaluating the patient with ALS/MND, the neurologist must
      consider a number of other motor neuron disorders and related motor syndromes
      that may have clinical features resembling ALS/MND. The revised Airlie House-El
      Escorial diagnostic criteria have been established through the consensus of
      experts meeting at workshops. However, by definition, using these criteria a
      patient is likely to have fairly advanced disease at the time of a definitive
      ALS/MND diagnosis. The reasons for the difficulty in making an early ALS/MND
      diagnosis are several. No surrogate diagnostic marker currently exists for
      ALS/MND. ALS/MND at its onset is heterogeneous in clinical presentation, its
      clinical course is variable, and several clinical variants are recognized. In
      addition, certain motor syndromes, such as monomelic amyotrophy, postpolio
      muscular atrophy, and multifocal motor neuropathy, can clinically mimic ALS/MND.
      Therefore, not only may the diagnosis of ALS/MND be clinically missed in the
      early stages, but worse, the patient may be wrongly labeled as having ALS/MND.
      The diagnosis of ALS/MND requires a combination of upper motor neuron (UMN) and
      lower motor neuron (LMN) involvement. Motor syndromes in which the deficit is
      restricted to the UMN or LMN through the entire course of the disease are
      described as atypical MND in this review. Approximately 5% of patients with
      ALS/MND have overt dementia with a characteristic frontal affect. ALS/MND with
      parkinsonism and dementia is rare outside the western Pacific region. The
      clinical course of motor disorder in these overlap syndromes does not differ from
      that in typical ALS/MND.

PMID- 11442327
TI  - Spinal muscular atrophy.
AB  - The spinal muscular atrophies are a group of mostly inherited disorders
      selectively affecting the lower motor neuron. There is a wide degree of clinical
      and genetic heterogeneity that must be taken into account when giving prognostic
      information. Autosomal recessive childhood proximal SMA is the commonest form and
      is due to mutations in a gene encoding a novel protein, SMN, that appears to play
      a critical role in RNA metabolism but has also been shown to interact with actin
      binding proteins and mediators of programmed cell death. The identification of
      the genetic basis of SMA has resulted in advances for prenatal diagnosis and in
      new insights into motor neuron biology. The chromosomal location of two of the
      rarer dominant forms of SMA has been found. Identification of the molecular
      pathophysiology of lower motor neuron syndromes can be expected to aid in the
      development of therapy for these disabling disorders.

PMID- 11442328
TI  - Progressive spastic paraparesis: hereditary spastic paraplegia and its relation
      to primary and amyotrophic lateral sclerosis.
AB  - The syndrome of insidiously progressive spastic weakness of both legs occurs in a
      number of etiologically distinct disorders including hereditary spastic
      paraplegia (HSP), primary lateral sclerosis (PLS), and sometimes in amyotrophic
      lateral sclerosis (ALS). This review summarizes the clinical and pathologic
      relationship between these disorders.

PMID- 11442329
TI  - Tracing Woody Guthrie and Huntington's disease.
AB  - Tracing the outlines of Woody Guthrie's life can be maddening. His outpouring of
      songs, words, and images attests to the rare creative spirit which possessed him
      like a devil, or angel, more often both. He was a figure which many of us hold
      dear as an emblematic American symbol of outspoken and independence-minded social
      consciousness. Drawn from Guthrie's collection of published and unpublished
      material in the Woody Guthrie Archives, including song lyrics, poems, prose,
      artwork--in short, every imaginable form of manuscript--the shadows that form and
      delineate Guthrie's life keep moving, much like dancing flames reflecting off a
      wall, illuminating some details while obscuring others. Guthrie, of course, had
      no choice about Huntington's disease (HD) or how it would impact his life.
      Characteristically, he moved with it, sang with it, and even danced with it. When
      HD finally silenced Guthrie in 1967, it nevertheless spurred his second wife,
      Marjorie Mazia, to action-action which continues today with the commitment and
      work of the Huntington's Disease Society of America (HDSA). Was it tragic? Or
      just the natural course of the disease? The interplay between artistry,
      inspiration, and devastation is what we explore here.

PMID- 11442330
TI  - Growth factors: roles in andrology.
AB  - Mesenchymal-epithelial interactions are extremely important during growth and
      development and in the functional cytodifferentiation of male sex accessory
      organs. Interactions between mesenchyme and epithelium occur mainly through a
      paracrine action that is mediated by various growth factors. The role of
      androgens is very important for these organs and the androgenic effect is
      mediated by paracrine interactions. A number of growth factors have been studied
      in prostate and seminal vesicles from mice, rats, and humans because they are
      potent mediators of cellular proliferation, differentiation, and death. This
      review provides an overview of current knowledge about growth factors involved in
      the development of male sex accessory organs, with particular emphasis on the
      prostate.

PMID- 11442331
TI  - Sperm processing: glass wool column filtration.
AB  - The cervical mucus selectively allows only progressively motile sperm of normal
      shape and size to penetrate and migrate through the cervix. The glass wool column
      filtration (GWCF) method for sperm processing, proposed in 1977 and later
      modified and standardized in 1986, selects such a sperm population in vitro.
      Sperm recovered from GWCF is significantly higher in quality than the original
      ejaculate. GWCF processing is reliable and highly repeatable, and when compared
      to other sperm processing techniques, GWCF yields significantly higher sperm
      quality. Sperm penetration into denuded hamster oocytes improves significantly
      with GWCF, while binding to human zona pellucida also occurs in higher numbers.
      IVF outcome also increases as compared to other processing techniques. GWCF,
      based on proven clinical success, is therefore invaluable for sperm processing.

PMID- 11442332
TI  - Nucleons II: cryopreservation and metabolic activity.
AB  - The establishment of intracytoplasmatic sperm injection (ICSI) as a routine
      procedure in assisted fertilization has been used in the treatment of male
      infertility. The major technical problem that has arisen with the use of immotile
      sperm for ICSI has been differentiating between live and dead cells. Nucleons
      from human, pig, hamster, mouse, rat, and bull have been able to induce their
      chromatin decondensation by the action of heparin/GSH. Cryopreservation is
      deleterious to sperm function, killing more than 50% of the spermatozoa during
      the process. Nucleon cryostorage was performed at 5 and -5 degrees C and analyzed
      for total area (mu2), perimeter (mu), width (mu), and length (mu), using
      Metamorph Imaging System software. On the other hand, fluorescein diacetate (FDA)
      is hydrolyzed by intracellular estereases to produce fluorescein, which exhibits
      green fluorescence when excited by blue light. This fact is a striking result
      since the presence of this metabolic activity opens the possibility to select the
      nucleons for ICSI. In the present study, the authors decided to search for a
      suitable metabolic test, which might reflect the metabolism and viability of
      these chromatin structures. This is a simple cryostorage technique that after
      months of cryopreservation, allow the use of nucleons for ICSI with suitable
      fertilization and pregnancies rates.

PMID- 11442333
TI  - Concentration of granulocyte elastase in seminal plasma is not associated with
      sperm motility.
AB  - Although elastase could affect sperm motility in vitro, secretory leukocytes
      protease inhibitor (SLPI) prevents sperm from being attacked by elastase. The
      authors investigated the correlations of elastase level with sperm motility and
      SLPI level in vivo. Semen samples (n = 116) were collected and centrifuged after
      semen analysis. Elastase and SLPI levels were determined by an enzyme
      immunosorbent assay. Samples were classified by elastase levels into low (<250
      ng/mL), moderate (250-1,000 ng/mL), and high elastase groups (> or =1,000 ng/mL).
      Elastase levels (range, 2.8-23,974.4 ng/mL) were not associated with sperm
      motility. The median SLPI level in the high elastase group was 15,900 ng/mL
      (range, 2.860-46,900 ng/mL). However, there was no significant correlation
      between elastase and SLPI levels in seminal plasma. Since SLPI forms a 1:1
      complex with elastase, these results suggest that seminal plasma has a sufficient
      amount of SLPI to protect spermatozoa from elastase.

PMID- 11442334
TI  - Electron microscopic observations of mouse sperm whole mounts after extraction
      for nuclear matrix and intermediate filaments.
AB  - Nuclear matrix and intermediate filaments (NM-IF) can be isolated by sequential
      treatment with non-ionic detergent, high salt. and nuclease. Extracted cells are
      easily observed by unembedded whole-mount transmission electron microscopy.
      Different somatic cell types have been subjected to this procedure and retained
      their essential architecture. To our knowledge, this work describes the first
      application of NM-IF extraction to sperm. After chemical dissection the general
      appearance of mouse sperm cells was preserved, except for head-from-neck
      separation in some cases. The cell membrane, acrosome and mitochondria were not
      present. The nucleus showed no apparent changes and revealed no details excepting
      pore complexes in the posterior part. Tissue-specific cytoskeletal elements
      (perforatorium, postacrosomal sheath, capitulum, segmented columns, outer dense
      fibers, submitochondrial reticulum, annulus, and fibrous sheath) were retained,
      which permitted a parallel between them and intermediate filaments of somatic
      cells. Tail microtubules were also relatively well preserved, showing high
      intrinsic stability. Cell structures could be observed well, with some details in
      the tail even better visible than in ultrathin sections. Observation of mouse
      sperm whole mounts after NM-IF extraction not only revealed intermediate filament
      like properties of their cytoskeletal elements but also offered an additional
      viewpoint to sperm ultrastructure.

PMID- 11442335
TI  - Heparin and glutathione II: correlation between decondensation of bull sperm
      cells and its nucleons.
AB  - The correlation between the kinetics of bull sperm nuclear and nucleon
      decondensation induced by the action of physiological concentrations of
      heparin/GSH was studied. Sperm and nucleon suspensions were incubated at 37
      degrees C in salt medium, at a constant concentration of either heparin or GSH
      and increasing concentrations of the other reagent. Even though nucleons are
      pretreated with DTT/CTAB, when they are incubated alone with GSH for 96 h, they
      remain intact, no matter which concentration is employed, and it was impossible
      to observe the slightest sign of nuclei decondensation. Therefore, rupture of
      disulfide bridges is not the main mechanism to induce nuclei decondensation and
      perhaps the GSH role resides in potentate the heparin effect by increasing its
      negative charge. Nevertheless, nucleons reach 95% of chromatin decondensation in
      the presence of heparin plus GSH or heparin alone. The fact that the correlation
      between heparin and GSH concentrations needed to induce sperm nuclei
      decondensation was 3- to 4-fold greater that in nucleons might be due to the
      complete lack of nucleon membranes. Heparin/GSH seem to induce nuclei
      decondensation by an ionic chromatin charge neutralization mechanism.

PMID- 11442336
TI  - Pig sperm membrane integrity evaluated by lectin labeling.
AB  - Sperm integrity is one of the most carefully examined characteristics for
      artificial insemination in humans and mammals. Techniques have been developed to
      assess the sperm plasma membrane integrity. Some of them need a well-trained
      evaluation for correctness, as is the case of the triple stain technique; others
      are time-consuming and need special equipment, varying from specially adapted
      microscopes to computer-based analyzers. The authors report the use of
      fluorescein-labeled peanut agglutinin plus a fluorescein extender that permits an
      easy evaluation for pig spermatozoa membrane integrity. Sperm integrity in pigs
      was evaluated before and after zona pellucida-induced acrosome reaction in
      capacitated sperm. The sperm acrosome reaction was affected when the zona
      pellucida was reduced.

PMID- 11442337
TI  - Association of selenoprotein P with testosterone production in cultured Leydig
      cells.
AB  - Selenoprotein P, a plasma selenoprotein, is thought to act as an antioxidant in
      the testis, similar to glutathione peroxidase. mRNA encoding selenoprotein P was
      selectively expressed by Leydig cells, suggesting participation in testosterone
      production. On the other hand, testosterone production has been linked to O2
      toxicity in cultured Leydig cells. The authors, therefore, examined changes in
      selenoprotein P mRNA expression and testosterone production following stimulation
      by a stable analog cyclic adenosine 3',5'-monophosphate (cAMP) in cultured Leydig
      cells (MLTC-1 cells) under normal O2 concentrations. Selenoprotein P mRNA was
      analyzed by Northern blotting, while testosterone concentration in culture medium
      was measured by radioimmunoassay. When cAMP was added to cultures at 0, 0.01,
      0.1, or 1 mM, selenoprotein P mRNA expression showed dose-dependent stimulation.
      cAMP was added at 0.1 mM to cultures, and the selenoprotein P mRNA expression and
      testosterone concentration were evaluated after incubation times of 2, 5, 9, 15,
      or 24 h. Selenoprotein P mRNA expression was maximal at 9 h. Testosterone
      concentration in the medium also increased, becoming maximal at 15 h.
      Selenoprotein P induced in Leydig cells following cAMP stimulation may counteract
      O2 toxicity from cAMP-mediated increases in testosterone production.

PMID- 11442338
TI  - GnRH and hCG tests in healthy adolescents and adults.
AB  - With the aim of obtaining reference values of GnRH test and of hCG test in a
      Venezuelan population, the authors evaluated the response of the pituitary LH and
      FSH to the GnRH action in 48 adolescents and 43 adults. Also, in 22 adolescents
      and in 22 adults from the same sample they evaluated the hCG effect on the
      gonadal steroids secretion. The maximum LH increment was obtained 30 min after
      GnRH stimulation, independently from the patients' age and their sexual
      development. FSH maximum increment was obtained 60 min after GnRH in the adults;
      meanwhile, the FSH maximum increment was obtained 30 min after GnRH stimulation
      in the Tanner stage 4 adolescents, and 90 min post-GnRH in the Tanner 5
      adolescents. The gonadal steroid secretion 2, 24, 48, and 72 h post-hCG was
      significantly lower in the Tanner 4 adolescents. The gonadal steroid response
      post-hGC stimulation in the Tanner 5 adolescent group was similar to the one
      obtained in the adults. In late puberty the LH response to GnRH stimulus is not
      related either to age or to sexual development, contrary to the FSH response
      obtained after GnRH and the gonadal steroid response after hCG stimulus, both of
      which are related to age and patients' sexual development.

PMID- 11442339
TI  - Spontaneous nisin-resistant Listeria monocytogenes mutants with increased
      expression of a putative penicillin-binding protein and their sensitivity to
      various antibiotics.
AB  - A concern regarding the use of bacteriocins, as for example the lantibiotic
      nisin, for biopreservation of certain food products is the possibility of
      resistance development and potential cross-resistance to antibiotics in the
      target organism. The genetic basis for nisin resistance development is as yet
      unknown. We analyzed changes in gene expression following nisin resistance
      development in Listeria monocytogenes 412 by restriction fragment differential
      display. The mutant had increased expression of a protein with strong homology to
      the glycosyltransferase domain of high-molecular-weight penicillin-binding
      proteins (PBPs), a histidine protein kinase, a protein of unknown function, and
      ClpB (putative functions from homology). The three former proteins had increased
      expression in a total of six out of 10 independent mutants originating from five
      different wild-type strains, indicating a prevalent nisin resistance mechanism
      under the employed isolation conditions. Increased expression of the putative PBP
      may affect the cell wall composition and thereby alter the sensitivity to cell
      wall-targeting compounds. The mutants had an isolate-specific increase in
      sensitivity to different beta-lactams and a slight decrease in sensitivity to
      another lantibiotic, mersacidin. A model incorporating these observations is
      proposed based on current knowledge of nisin's mode of action.

PMID- 11442340
TI  - Penicillin-resistant Streptococcus pneumoniae in metropolitan New York hospitals:
      case control study and molecular typing of resistant isolates.
AB  - During the 4-month period from January to April, 1998, 476 patients with
      Streptococcus pneumoniae infections were detected in 12 metropolitan New York
      hospitals and 112 penicillin-resistant (PRP) isolates (24%) were identified in 11
      institutions. A case control study of 100 patients with penicillin-resistant and
      susceptible pneumococci from four of the widely dispersed hospitals revealed a
      high incidence of underlying medical illnesses in adult patients (74%), a
      preponderance of patients with pneumonia (63%), and a majority of patients who
      had underlying risk factors for pneumonia or invasive disease (51%). In this
      limited case control study, no difference was noted between cases and controls
      regarding known risk factors for penicillin-resistant pneumococcal infections.
      The percentage of single-patient PRP isolates varied among individual hospitals
      but the mean percentages of PRP from the four participating University Medical
      Centers and seven community hospitals were similar: 26% and 22% respectively. By
      E-test, 60% and 26% were high-level penicillin and ceftriaxone resistant,
      respectively. Pulsed-field gel electrophoresis identified 26 chromosomal
      macrorestriction patterns among the 103 PRP isolates available for analysis, but
      almost half (50 isolates or 48%) of these belong to two drug-resistant
      internationally spread clones, SP(23)-1 and SP(9/14)-3, that were detected in all
      hospitals and were recovered from invasive and noninvasive sites in both children
      and adults.

PMID- 11442341
TI  - Presence of international multiresistant clones of Streptococcus pneumoniae in
      Colombia.
AB  - In Colombia, penicillin resistance of Streptococcus pneumoniae invasive isolates
      recovered from children less than 5 years old has increased from 10% in 1994 to
      49.4% in 1999, suggesting the circulation of international resistant clones in
      the country. A total of 167 S. pneumoniae invasive isolates with diminished
      susceptibility to penicillin (DSP) were studied. The techniques used were pulsed
      field gel electrophoresis (PFGE) and restriction fragment length polymorphism
      (RFLP) of penicillin-binding proteins (PBPs) genes (2B, 2X, and 1A). Forty-nine
      serotype 23F isolates were grouped in two clusters: 15 (31%) multiresistant
      isolates showed PFGE pattern A and PBP I profile, thus making them
      indistinguishable from Spain23F-1 clone, and 34 (69%) with PFGE pattern C, PBP II
      profile, and intermediate level resistance (ILR) to penicillin and TMP-SMX,
      features unique to a Colombian clone. Fifty-five serotype 14 isolates were
      assigned to PFGE B pattern, PBP III profile, having high-level resistance to
      penicillin, and TMP-SMX, similar to the France9V variant 14. This same pattern
      was present in five capsular type 9V isolates. Four serotype 14 isolates were
      assigned to PFGE pattern F, and appeared to be similar to Slovakia(14)-10 PFGE
      pattern, although they had different PBP profiles. Nine capsular type 6B and one
      6A isolates belonged to PFGE pattern M, similar to Spain6B-2, although they
      showed different PBP profiles. The remaining 44 isolates, corresponding to
      serotypes 14, 6B, 19F, and 34, showed variable PFGE and PBP patterns. These
      results show that as many as two international clones may be circulating in
      Colombia as well as a unique, widely distributed 23F clone with ILR to
      penicillin. Additionally, some Colombian isolates capsular type 14 and 6B might
      be related to Slovakia(14)-10 Spain6B-2 clones, respectively.

PMID- 11442342
TI  - Macrolide resistance in Streptococcus pyogenes isolates from throat infections in
      the region of Aachen, Germany.
AB  - Macrolide-resistance was assessed in 216 consecutive Streptococcus pyogenes
      isolates from throat infections in the region of Aachen, Germany. Seventeen
      isolates were resistant to erythromycin: 12 isolates revealed a macrolide (M)
      phenotype and harbored mefA, and five strains expressed an inducible macrolide
      lincosamide-streptogramin B (MLSB) phenotype of which four strains harbored
      ermA(TR) and one strain contained ermB(AM). Telithromycin (HMR 3647) and
      quinupristin/dalfopristin remained active particularly against the ermA(TR)
      containing S. pyogenes isolates studied. Random amplified polymorphic DNA
      analysis identified multiple clones among erythromycin-resistant strains, but did
      not discriminate beyond the emm-type. mefA was present in three isolates either
      with emm2, emm12, or emm75, and in nine isolates with emm4. All four strains with
      ermA(TR) contained emm77, and the single strain with ermB(AM) harbored emm1.
      Despite the relative low rate of macrolide-resistance, these data suggest that at
      least three different macrolide-resistance determinants are prevalent in Germany
      and that mefA has spread rapidly into multiple clones of S. pyogenes.

PMID- 11442343
TI  - Detection and typing of extended-spectrum beta-lactamases in clinical isolates of
      the family Enterobacteriaceae in a medical center in Turkey.
AB  - To determine and type the extended-spectrum beta-lactamases (ESBLs) among the
      family Enterobacteriaceae in a medical center, a total of 668 clinical isolates
      were screened. Of the 668 isolates, the 80 strains were presumptively defined as
      ESBL producers according to the result of disk method using ESBL marker
      antibiotics (aztreonam, ceftazidime, and cefoxitin). These 80 strains were
      retested with the double-disk synergy test (DDST), the E-test ESBL strip, a 5
      microg ceftazidime disk, and agar dilution MICs of ceftazidime with and without
      clavulonic acid. Isoelectric focusing was performed to confirm ESBL production
      and type the beta-lactamases. By evaluation of the results of all tests used for
      ESBL detection together with isoelectric focusing, 33 (4.9%) of the 668 isolates
      were described as ESBL producer. The positive results of the agar dilution test,
      DDST, the E-test strip, and 5-microg ceftazidime disk were 32, 26, 27, and 26 of
      the 33 strains, respectively. ESBL positivity was 48.8% in Klebsiella species,
      15.4% in Citrobacter species, 4.9% in Enterobacter species and 1.1% in
      Escherichia coli strains. The ESBL enzymes frequently determined were SHV-2/6
      like (pI 7.6), SHV-5-like (pI 8.2), SHV-4-like (pI 7.8), and SHV-3-like (pI 7).
      SHV-derived enzymes were commonly observed in Klebsiella spp whereas TEM-related
      enzymes were seen in E. coli strains. The results of this study indicated that
      SHV-2/6-derived (pI 7.6) ESBL expression among the isolates of the family
      Enterobacteriaceae is an important problem in our medical center.

PMID- 11442344
TI  - Prevalence and characteristics of nim genes encoding 5-nitroimidazole resistance
      among Bacteroides strains isolated in Morocco.
AB  - We report here an evaluation of the dissemination of nim genes, encoding 5
      nitroimidazoles resistance, among Bacteroides clinical strains isolated in
      Morocco. This study was done using a PCR method. Among 60 strains studied, nine
      contain a copy of a nim gene. The sequence determination of these genes showed
      that they are homologous to three nim genes previously characterized in strains
      isolated in France: nimB (five genes), nimC (three genes), and nimA (one gene).
      Although the nimA and nimC genes were previously identified on plasmids pIP417
      and pIP419, respectively, we found here that they have a chromosomal location.
      The MICs of three 5-nitroimidazole antibiotics (metronidazole, ornidazole, and
      tinidazole) of the nim gene-containing strains were very low (0.5-2 microg/ml),
      indicating that the nim genes were not efficiently expressed in these clinical
      isolates.

PMID- 11442345
TI  - The Swedish experience of the 1986 year ban of antimicrobial growth promoters,
      with special reference to animal health, disease prevention, productivity, and
      usage of antimicrobials.
AB  - In Sweden the use of antimicrobial growth promoters (AMGP) was banned in 1986.
      The experiences gained from that ban are presented. In production of slaughter
      pigs, specialized beef, and turkeys, no negative clinical effects were reported
      as a consequence of the ban. In broiler chicken production, expected problems
      with necrotic enteritis were prevented by a continuous use of antibiotics,
      largely to the same extent during the first 2 years after the ban. Following the
      implementation of results from experimental activities during that period, the
      general usage of antimicrobials could be stopped and expected problems with
      outbreaks of necrotic enteritis was prevented. In piglet production, significant
      clinical problems emerged that created a demand for antibiotic-medicated feed at
      therapeutic dosages. During the subsequent 4-year period, the use of antibiotics
      increased, involving up to 75% of the pigs. Thereafter, the use of antibiotics
      decreased because of improved management, and could be halved in 1993 followed by
      a gradual further decrease supported by the addition of zinc oxide to the feed.
      In 1998, compared to 1994, the total use of zinc decreased by 90%. In 1998/1999,
      only 5% of weaning piglet producing herds used antibiotic medicated feed and 17%
      used zinc. The AMGP ban has shown that under good production conditions it is
      possible to reach good and competitive production results for the rearing of
      poultry, calves, and pigs without the continuous use of AMGP. As a result of the
      ban and a focus on disease prevention and correct use of antimicrobials, the
      total use of antibacterial drugs to animals in Sweden decreased by approximately
      55% during the last 13-year period, and a relatively low prevalence of
      antimicrobial resistance has been maintained.

PMID- 11442346
TI  - Self-transmissible multidrug resistance plasmids in Escherichia coli of the
      normal intestinal flora of healthy swine.
AB  - The resistance genes and their surroundings on three self-transmissible plasmids
      found in Escherichia coli of the enteric normal flora of healthy pigs have been
      characterized. The resistance elements found are similar to those commonly found
      in clinical isolates, like the transposon Tn1721 including the Tet A tetracycline
      resistance determinant, Tn10 with the Tet B determinant, Tn21 including a class 1
      integron with the aadA1a cassette inserted, sulII encoding sulfonamide
      resistance, and the strA-strB genes responsible for streptomycin resistance. The
      plasmids were able to mobilize into various recipients, including swine
      pathogens, zoonotic bacteria, and commensals when conjugation experiments were
      carried out. Transfer of plasmids did not require optimal conditions concerning
      nutrition and temperature as plasmids were transferred in 0.9% saline at room
      temperature, suggesting that in vivo transfer might be possible. This study shows
      that transferable resistance elements appearing in normal flora bacteria from
      animals are similar to those commonly found in clinical isolates of human origin.
      The results indicate a probable communication between pathogens and the normal
      flora with respect to exchange of resistance factors.

PMID- 11442347
TI  - Trends in antimicrobial resistance of Salmonella isolated from animals, foods of
      animal origin, and the environment of animal production in Canada, 1994-1997.
AB  - The purpose of our study was to determine the occurrence, magnitude, trends, and
      relationships regarding antibiotic resistance of Salmonella isolated from
      animals, animal food products, and the environment of animals. We examined 621
      strains of 67 different serovars isolated in 1994, 721 strains of 75 different
      serovars isolated in 1995, 1,219 strains of 83 different serovars isolated in
      1996, and 1,336 Salmonella strains of 92 different serovars isolated in 1997, for
      resistance to 17 antibiotics at one to three different concentrations with the
      agar dilution method. The overall resistance magnitude regressed from 9.2% in
      1994 to 8.1% in 1997. Resistance to streptomycin (30.4% of 3,897 isolates),
      tetracycline (27.3%), and sulfisoxazole (23.7%) was highest. Resistance to
      streptomycin, tetracycline, kanamycin, and gentamicin declined during the 4-year
      period. Notable increases in resistance to ampicillin, chloramphenicol, and
      neomycin occurred during the 1994-1997 years. None of the isolates was resistant
      to amikacin. None of the isolates was resistant to ciprofloxacin at 1, 2, and 4
      microg/ml. Salmonella bredeney isolates from turkeys showed a decreased
      sensitivity to ciprofloxacin and were resistant at the low level of 0.125
      microg/ml, but none of these isolates was resistant at 1 microg/ml. Resistance to
      nalidixic acid correlated significantly with decreased sensitivity to
      ciprofloxacin; 122 of 127 (96%) isolates resistant to nalidixic acid at 32
      microg/ml were resistant to ciprofloxacin at 0.125 microg/ml but sensitive at 1
      microg/ml. Resistance to S. typhimurium to each of the seven antibiotics
      ampicillin, chloramphenicol, kanamycin, neomycin, streptomycin, sulfisoxazole,
      and tetracycline increased persistently during each of the years 1994-1997, but
      none of the S. typhimurium isolates showed decreased sensitivity to
      ciprofloxacin. Clinical isolates of Salmonella were twice as frequently resistant
      to the antimicrobials in the test panel than isolates obtained during surveys.
      Salmonella isolates from turkeys were more frequently resistant than isolates
      from pigs, cattle, and chickens.

PMID- 11442348
TI  - Annotated draft genomic sequence from a Streptococcus pneumoniae type 19F
      clinical isolate.
AB  - The public availability of numerous microbial genomes is enabling the analysis of
      bacterial biology in great detail and with an unprecedented, organism-wide and
      taxon-wide, broad scope. Streptococcus pneumoniae is one of the most important
      bacterial pathogens throughout the world. We present here sequences and
      functional annotations for 2.1-Mbp of pneumococcal DNA, covering more than 90% of
      the total estimated size of the genome. The sequenced strain is a clinical
      isolate resistant to macrolides and tetracycline. It carries a type 19F capsular
      locus, but multilocus sequence typing for several conserved genetic loci suggests
      that the strain sequenced belongs to a pneumococcal lineage that most often
      expresses a serotype 15 capsular polysaccharide. A total of 2,046 putative open
      reading frames (ORFs) longer than 100 amino acids were identified (average of
      1,009 bp per ORF), including all described two-component systems and aminoacyl
      tRNA synthetases. Comparisons to other complete, or nearly complete, bacterial
      genomes were made and are presented in a graphical form for all the predicted
      proteins.

PMID- 11442349
TI  - Tissue transglutaminase selectively modifies proteins associated with truncated
      mutant huntingtin in intact cells.
AB  - The cause of Huntington's disease (HD) is a pathological expansion of the
      polyglutamine domain within the N-terminal region of huntingtin. Neuronal
      intranuclear inclusions and cytoplasmic aggregates composed of the mutant
      huntingtin within certain neuronal populations are a characteristic hallmark of
      HD. However, how the expanded polyglutamine repeats of mutant huntingtin cause HD
      is not known. Because in vitro expanded polyglutamine repeats are excellent
      glutaminyl-donor substrates of tissue transglutaminase (tTG), it has been
      hypothesized that tTG may contribute to the formation of these aggregates in HD.
      However, an association between huntingtin and tTG or modification of huntingtin
      by tTG has not been demonstrated in cells. To examine the interactions between
      tTG and huntingtin human neuroblastoma SH-SY5Y cells were stably transfected with
      full-length huntingtin containing 23 (FL-Q23) (wild type) or 82 (FL-Q82) (mutant)
      glutamine repeats or a truncated N-terminal huntingtin construct containing 23
      (Q23) (wild type) or 62 (Q62) (mutant) glutamine repeats. Aggregates were rarely
      observed in the cells expressing full-length mutant huntingtin, and no specific
      colocalization of full-length huntingtin and tTG was observed. In contrast, in
      cells expressing truncated mutant huntingtin (Q62) there were numerous complexes
      of truncated mutant huntingtin and many of these complexes co-localized with tTG.
      However, the complexes were not insoluble structures. Further, truncated
      huntingtin coimmunoprecipitated with tTG, and this association increased when tTG
      was activated. Activation of tTG did not result in the modification of either
      truncated or full-length huntingtin, however proteins that were associated with
      truncated mutant huntingtin were selectively modified by tTG. This study is the
      first to demonstrate that tTG specifically interacts with a truncated form of
      huntingtin, and that activated tTG selectively modifies mutant huntingtin
      associated proteins. These data suggest that proteolysis of full-length mutant
      huntingtin likely precedes its interaction with tTG and this process may
      facilitate the modification of huntingtin-associated proteins and thus contribute
      to the etiology of HD.

PMID- 11442350
TI  - Distinct behavioral and neuropathological abnormalities in transgenic mouse
      models of HD and DRPLA.
AB  - Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA)
      are autosomal dominant, neurodegenerative disorders caused by the expansion of
      polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We
      have previously generated mouse models of these disorders, using transgenes
      expressed via the prion protein promoter. Here, we report the first direct
      comparison of abnormalities in these models. The HD mice show abbreviated
      lifespans (4-6 months), hypoactivity, and mild impairment of motor skills. The
      DRPLA mice show severe tremors, are hyperactive, and are profoundly
      uncoordinated. Neuropathological analyses reveal that the distribution of diffuse
      nuclear immunolabeling and neuronal intranuclear inclusions (NII's), in the CNS
      of both models, was remarkably similar. Cytoplasmic aggregates of huntingtin were
      the major distinguishing neuropathological feature of the HD mice; mutant
      atrophin-1 accumulated/aggregated only in the nucleus. We suggest that the
      distinct behavioral and neuropathological phenotypes in these mice reflect
      differences in the way these mutant proteins perturb neuronal function.

PMID- 11442351
TI  - A synaptic mechanism underlying the behavioral abnormalities induced by manganese
      intoxication.
AB  - In the present study we have characterized a rat model of manganese (Mn)
      intoxication leading to behavioral disinhibition in the absence of major motor
      alterations. These behavioral changes were associated with significantly
      increased brain Mn levels but were uncoupled to anatomical lesions of the
      striatum or to morphological and cytochemical changes of the nigrostriatal
      dopaminergic pathway. The analysis of this model at cellular level showed an
      enhanced dopaminergic inhibitory control of the corticostriatal excitatory
      transmission via presynaptic D2-like dopamine (DA) receptors in slices obtained
      from Mn-treated rats. Conversely, the use of agonists acting on presynaptic
      purinergic, muscarinic, and glutamatergic metabotropic receptors revealed a
      normal sensitivity. Moreover, membrane responses recorded from single
      dopaminergic neurons following activation of D2 DA autoreceptors were also
      unchanged following Mn intoxication. Thus, our findings indicate a selective
      involvement of the D2-like DA receptors located on glutamatergic corticostriatal
      terminals in this pathological condition and suggest that the behavioral symptoms
      described in the "early" clinical phase of manganism may be caused by an abnormal
      dopaminergic inhibitory control on corticostriatal inputs. The identification of
      the synaptic mechanism underlying the "early" phase of Mn intoxication might have
      a critical importance to understand the causes of the progression of this
      pathological condition towards an "established" phase characterized by motor
      abnormalities and anatomical lesions of the basal ganglia.

PMID- 11442352
TI  - Neuroprotective effect of a CNTF-expressing lentiviral vector in the quinolinic
      acid rat model of Huntington's disease.
AB  - Neurodegenerative diseases represent promising targets for gene therapy
      approaches provided effective transfer vectors. In the present study, we
      evaluated the effectiveness of LacZ-expressing lentiviral vectors with two
      different internal promoters, the mouse phosphoglycerate kinase 1 (PGK) and
      cytomegalovirus (CMV), to infect striatal cells. The intrastriatal injection of
      lenti-beta-Gal vectors lead to 207, 400 +/- 11,500 and 303,100 +/- 4,300 infected
      cells in adult rats, respectively. Importantly, the beta-galactosidase activity
      was higher in striatal extracts from PGK-LacZ-injected animals as compared to CMV
      LacZ animals. The efficacy of the system was further examined with a potential
      therapeutic gene for the treatment of Huntington's disease, the human ciliary
      neurotrophic factor (CNTF). PGK-LacZ- or PGK-CNTF-expressing viruses were
      stereotaxically injected into the striatum of rats, 3 weeks later the animals
      were unilaterally lesioned with 180 nmol of quinolinic acid (QA). Control animals
      displayed 148 +/- 43 apomorphine-induced rotations ipsilateral to the lesion 5
      days postlesion as compared to 26 +/- 22 turns/45 min in the CNTF-treated group.
      The extent of the striatal damage was significantly diminished in the CNTF
      treated rats as indicated by the 52 +/- 9.7% decrease of the lesion volume and
      the sparing of DARPP-32, ChAT and NADPH-d neuronal populations. These results
      further establish that lentiviruses may represent an efficient gene delivery
      system for the screening of therapeutic molecules in Huntington's disease.

PMID- 11442353
TI  - The frissonnant mutant mouse, a model of dopamino-sensitive, inherited motor
      syndrome.
AB  - The frissonnant (fri) mutation is an autosomic recessive mutation which
      spontaneously appeared in the stock of C3H mice. fri mutant mice have locomotor
      instability and rapid tremor. Since tremor ceases when mutant mice have sleep or
      are anaesthetized, and because of their obvious stereotyped motor behavior, these
      mice could represent an inherited Parkinsonian syndrome. We show here that the
      fri/fri mouse fulfills two out of the three criteria required to validate an
      experimental model of human disease, that is isomorphism, homology and
      predictivity. Indeed, fri/fri mice present an important motor deficit
      accompanying visible tremor and stereotypies. They display some memory deficits
      as in human Parkinson's desease. l-Dopa and apomorphine (dopaminergic agonists),
      ropinirole (selective D2 agonist), and selegiline (an monoamino-oxidase B [MAO-B]
      inhibitor) improve their clinical status. However, neither anatomopathological
      evidence of nigrostriatal lesion, nor decrease in tyrosine hydroxylase production
      could be seen.

PMID- 11442354
TI  - RNA editing at the Q/R site for the glutamate receptor subunits GLUR2, GLUR5, and
      GLUR6 in hippocampus and temporal cortex from epileptic patients.
AB  - Posttranscriptional editing of mRNA is a phenomenon that generates molecular
      heterogeneity and functional variety. With the intention to test if RNA editing
      plays a role in pathological processes, which contribute to seizure maintenance,
      we examined the ratio of the unedited (Q) to edited (R) form of the AMPA receptor
      subunit GluR2 and kainate receptor subunits GluR5 and GluR6 in the hippocampus
      and temporal cerebral cortex, both excised from patients with pharmacoresistant
      temporal lobe epilepsies. We compared the data with samples from nonepileptic
      human control tissue (autopsy tissue). The ratio of Q/R editing was analyzed by
      means of reverse transcription-polymerase chain reaction followed by a
      restriction enzyme assay. We found that the editing efficiency for the kainate
      receptor subunits GluR5 and GluR6 was significantly higher in temporal cortex
      than in normal controls. The alteration in GluR5 and GluR6 mRNA editing in the
      neocortical tissue may reflect an adaptive reaction of ongoing seizure activity
      to prevent excessive Ca(2+) influx.

PMID- 11442355
TI  - Subcellular mechanisms of presenilin-mediated enhancement of calcium signaling.
AB  - Mutations in presenilin-1 (PS1), the leading cause of early-onset, autosomal
      dominant familial Alzheimer's disease (FAD), enhance calcium signaling mediated
      by inositol 1,4,5-trisphosphate (IP3). To elucidate the subcellular mechanisms
      underlying this enhancement, we used high resolution line-scanning confocal
      microscopy to image elementary calcium release events ("puffs") in Xenopus
      oocytes expressing wild-type or mutant PS1. Here we report that mutant PS1
      rendered puffs more sensitive to IP3 and increased both the magnitude and the
      rate of calcium release during each event. These effects were not attributable to
      quantitative changes in the levels of IP3 receptors or their distribution on the
      ER, but were instead associated with an abnormal elevation of ER calcium stores.
      Together, our results suggest that the effects of mutant PS1 on calcium signaling
      are manifested predominantly at the level of the regulation of calcium stores
      rather than via perturbations in the numbers or activity of IP3-activated calcium
      release channels.

PMID- 11442356
TI  - Corticotropin-releasing hormone protects neurons against insults relevant to the
      pathogenesis of Alzheimer's disease.
AB  - We previously reported that mice over-expressing the human amyloid precursor
      protein gene with the double Swedish mutation of familial Alzheimer's disease
      (mtAPP), which exhibit progressive deposition of amyloid beta-peptide in
      hippocampal and cortical brain regions, have an impaired ability to maintain a
      sustained glucocorticoid response to stress. Corticotropin releasing hormone
      (CRH), which initiates neuroendocrine responses to stress by activating the
      hypothalamic-pituitary-adrenal (HPA) axis, is expressed in brain regions prone to
      degeneration in Alzheimer's disease. We therefore tested the hypothesis that CRH
      can modify neuronal vulnerability to amyloid beta-peptide toxicity. In primary
      neuronal culture, CRH was protective against cell death caused by an amyloid-beta
      peptide, an effect that was blocked by a CRH receptor antagonist and by an
      inhibitor of cyclic AMP-dependent protein kinase. The increased resistance of CRH
      treated neurons to amyloid toxicity was associated with stabilization of cellular
      calcium homeostasis. Moreover, CRH protected neurons against death caused by
      lipid peroxidation and the excitotoxic neurotransmitter glutamate. The level of
      mRNA encoding CRH was unchanged in mtAPP mouse brain, whereas the levels of mRNAs
      encoding glucocorticoid and mineralocorticoid receptors were subtly altered. Our
      results suggest that disturbances in HPA axis function can occur independently of
      alterations in CRH mRNA levels in Alzheimer's disease brain and further suggest
      an additional role for CRH in protecting neurons against cell death.

PMID- 11442357
TI  - Modulation (inhibition and augmentation) of complement receptor-3-mediated myelin
      phagocytosis.
AB  - The removal of damaged myelin is central to repair after injury to axons and in
      autoimmune demyelinating diseases. Complement receptor 3 (CR3/MAC-1) plays a
      major role in mediating the phagocytosis of damaged myelin by macrophages and
      microglia. We studied the modulation (inhibition and augmentation) of CR3/MAC-1
      mediated myelin phagocytosis by mAbs that bind to distinct epitopes of subunits
      alphaM and beta2 of CR3/MAC-1. mAb M1/70 anti-alpha(M) and mAb 5C6 anti-alpha(M)
      inhibited, whereas mAb M18/2 anti-beta2 augmented myelin phagocytosis. This mAb
      induced modulation of myelin phagocytosis occurred in the presence and absence of
      active complement. Inhibition induced by M1/70 or 5C6 did not add when the two
      were combined. Combining M1/70 or 5C6 with M18/2 reduced the augmentation induced
      by M18/2 alone. CR3/MAC-1-mediated myelin phagocytosis may thus be subjected to
      modulation between efficient and inefficient functional/activation states. These
      observations and conclusions may offer an explanation for the observed
      discrepancy between efficient myelin phagocytosis in experimental allergic
      encephalomyelitis and inefficient myelin phagocytosis after injury to CNS axons,
      although in both instances macrophages/microglia express CR3/MAC-1.

PMID- 11442358
TI  - Differential regulation of transcripts for dystrophin Isoforms, dystroglycan, and
      alpha3AChR subunit in mouse sympathetic ganglia following postganglionic nerve
      crush.
AB  - Previous data suggest that in mouse superior cervical ganglion (SCG) the
      dystrophin-dystroglycan complex may be involved in the axotomy-induced
      intraganglionic synapse remodeling. Here we analyzed the levels of mRNAs encoding
      dystrophins, dystroglycan (Dg), and the alpha3 subunit of the nicotinic
      acetylcholine receptor (alpha3AChR) in mouse SCG at various postaxotomy
      intervals. We found that axotomy downregulates the levels of transcripts for
      molecules related to synaptic transmission (alpha3AChR) and those presumably
      involved in postsynaptic apparatus organization (dystrophin isoforms) and
      upregulates the transcript encoding Dg, which, by binding dystrophin, bridges the
      actin cytoskeleton and several extracellular matrix proteins and may thus be
      involved in postaxotomy neuronal recovery. The observed transcriptional
      modulation of the components of dystrophin-dystroglycan complexes indicates their
      involvement in injury-induced neuronal plasticity and suggests a role in other
      forms of plasticity such as those required in learning and memory, functions
      often impaired in Duchenne muscular dystrophy patients.

PMID- 11442359
TI  - Hypocretin levels in sporadic and familial cases of canine narcolepsy.
AB  - Familial and sporadic forms of narcolepsy exist in both humans and canines.
      Mutations in the hypocretin receptor 2 gene (Hcrtr 2) cause canine familial
      narcolepsy. In humans, mutations in hypocretin-related genes are rare, but
      cerebrospinal fluid (CSF) hypocretin-1 is undetectable in most sporadic cases.
      Using the canine model, we investigated ( 1 ) whether hypocretin deficiency is
      involved in sporadic cases and ( 2 ) whether alterations in hypocretin neurons or
      ligand levels also contribute to the phenotype in Hcrtr 2 mutants. We found that
      hypocretins were undetectable in the brains of three of three and the CSF of two
      of two sporadic narcoleptic dogs tested. In contrast, hypocretin levels were not
      altered in brains and CSF of genetically narcoleptic Dobermans, and hypocretin
      containing neurons were of normal appearance. Therefore, multiple hypocretin
      related etiologies are likely to be involved in canine narcolepsy. The presence
      of hypocretin peptides in Hcrtr 2-mutated animals suggests that neurotransmission
      through Hcrtr 1 may be intact, arguing for a preferential importance of Hcrtr 2
      mediated function in narcolepsy.

PMID- 11442360
TI  - Lack of nigral pathology in transgenic mice expressing human alpha-synuclein
      driven by the tyrosine hydroxylase promoter.
AB  - alpha-Synuclein has been identified as a major component of Lewy body inclusions,
      which are one of the pathologic hallmarks of idiopathic Parkinson's disease.
      Mutations in alpha-synuclein have been found to be responsible for rare familial
      cases of Parkinsonism. To test whether overexpression of human alpha-synuclein
      leads to inclusion formation and neuronal loss of dopaminergic cells in the
      substantia nigra, we made transgenic mice in which the expression of wild-type or
      mutant (A30P and A53T) human alpha-synuclein protein was driven by the promoter
      from the tyrosine hydroxylase gene. Even though high levels of human alpha
      synuclein accumulated in dopaminergic cell bodies, Lewy-type-positive inclusions
      did not develop in the nigrostriatal system. In addition, the number of nigral
      neurons and the levels of striatal dopamine were unchanged relative to non
      transgenic littermates, in mice up to one year of age. These findings suggest
      that overexpression of alpha-synuclein within nigrostriatal dopaminergic neurons
      is not in itself sufficient to cause aggregation into Lewy body-like inclusions,
      nor does it trigger overt neurodegenerative changes.

PMID- 11442361
TI  - Bis(phthalocyaninato)gadolinium(III) hexacyanobutadienide(1-), [GdPc2]+[C4(CN)6]
      . An electron transfer salt with four paramagnetic sites.

PMID- 11442362
TI  - Invited award contribution for ACS Award in Inorganic Chemistry. Geometric and
      electronic structure contributions to function in bioinorganic chemistry: active
      sites in non-heme iron enzymes.
AB  - Spectroscopy has played a major role in the definition of structure/function
      correlations in bioinorganic chemistry. The importance of spectroscopy combined
      with electronic structure calculations is clearly demonstrated by the non-heme
      iron enzymes. Many members of this large class of enzymes activate dioxygen using
      a ferrous active site that has generally been difficult to study with most
      spectroscopic methods. A new spectroscopic methodology has been developed
      utilizing variable temperature, variable field magnetic circular dichroism, which
      enables one to obtain detailed insight into the geometric and electronic
      structure of the non-heme ferrous active site and probe its reaction mechanism on
      a molecular level. This spectroscopic methodology is presented and applied to a
      number of key mononuclear non-heme iron enzymes leading to a general mechanistic
      strategy for O2 activation. These studies are then extended to consider the new
      features present in the binuclear non-heme iron enzymes and applied to understand
      (1) the mechanism of the two electron/coupled proton transfer to dioxygen binding
      to a single iron center in hemerythrin and (2) structure/function correlations
      over the oxygen-activating enzymes stearoyl-ACP Delta9-desaturase, ribonucleotide
      reductase, and methane monooxygenase. Electronic structure/reactivity
      correlations for O2 activation by non-heme relative to heme iron enzymes will
      also be developed.

PMID- 11442363
TI  - Influence of chelate effects on the water-exchange mechanism of
      polyaminecarboxylate complexes of iron(III).
AB  - The effect of temperature and pressure on the water-exchange reactions of
      complexes of the type [FeIII(L)(H2O)x]n-, where L = edta4-
      (ethylenediaminetetraacetate), Hedta3- (monoprotonated form of edta), cdta4-
      (trans-1,2-diaminocyclohexanetetraacetate), edds4- (s,s
      ethylenediaminedisuccinate), 1,3-pdta4- (1,3-propylenediaminetetraacetate), and
      alpha,beta-eddadp4-(alpha,beta-ethylenediaminediaceatedipropionate), was studied
      by employing 17O NMR techniques. The effect of potentially hexadentate ligands,
      covering a systematic variation of the size, substituents, and overall
      coordination geometry, on iron(III) complexes was investigated in terms of the
      lability of the coordinated water and the underlying exchange mechanism. For most
      of the systems studied, the results are in agreement with a dissociatively
      activated water-exchange mechanism for the seven-coordinate complexes. The
      absolute magnitudes of the volumes of activation are small and fit an I(d)
      mechanism. The results contribute to a better understanding of the nature,
      reactivity, and substitution mechanism of the selected complexes in solution.

PMID- 11442364
TI  - Reversible osmium(VI) nitrido to osmium(II) ammine interconversion in complexes
      containing polypyrazolyl ligands.
AB  - This paper describes the 4e-/3H+ interconversion between NH3 and N3-, which is
      reversible in the coordination spheres of Os complexes containing either tpm (tpm
      = tris(1-pyrazolyl)methane) or Tp (Tp = hydrotris(1-pyrazolyl)borate anion)
      ligands. Electrochemical or chemical reduction of the nitrido complexes
      [Os(VI)(tpm)(Cl)2(N)]+ (1) and Os(VI)(Tp)(Cl)2(N) (2) in acidic aqueous solution
      gives the corresponding Os(II)-ammine complexes, which, after air oxidation and
      workup, are isolated and structurally characterized as
      [Os(III)(tpm)(Cl)2(NH3)](PF6) (3) and Os(III)(Tp)(Cl)2(NH3) (4). The Os(III)
      ammine complexes are reoxidized electrochemically to the nitrido complexes by
      stepwise mechanisms involving the loss of both electrons and protons and
      sequential Os(III-->IV) and Os(IV-->VI) oxidations.

PMID- 11442365
TI  - Structural analysis and magnetic properties of the 1D and 3D compounds
      [Mn(dca)2nbipym] (M = Mn, Cu; dca = dicyanamide; bipym = bipyrimidine; n = 1,2).
AB  - Compounds [Mn(dca)2bipym] (1), [Cu2(dca)4bipym] (2), and [Mn2(dca)4bipym] (3)
      have been synthesized and structural (2, 3) and magnetically characterized.
      Compound 1 is isomorphous with [Mn(dca)2bipy]. Compound 2 crystallizes in the
      monoclinic P2(1)/c space group, Z = 4, with a = 7.5609(9), b = 11.477(42), and c
      = 11.792(2) A and beta = 106.565(6) degrees. Compound 3 crystallizes in the
      monoclinic system, space group P2(1)/n, with a = 7.396(3) A, b = 11.498(7) A, and
      c = 12.349(9) A and beta = 106.61(5) degrees. While compound 1 is one
      dimensional, with the manganese(II) ions bridged by double mu1,5-dicyanamide
      ligands, the structural arrangement in compounds 2 and 3 is three-dimensional
      based on ladder-like moieties. These units, whose steps are bipym groups, extend
      through mu1,5-dca bridges and are connected to another four on the plane
      perpendicular to the extension of the ladders to form the 3D arrangement.
      Magnetic susceptibility measurements show antiferromagnetic couplings in all
      cases, increasing for 1, 3, and 2, respectively.

PMID- 11442366
TI  - High-resolution luminescence and absorption spectroscopy of Cs2GeF6:Os4+.
AB  - The luminescence spectrum of the Os4+ dopant ion occupying O(h) sites of the
      Cs2GeF6 host shows three sets of resolved transitions in the near-infrared at
      approximately 12000, 9000, and 6700 cm(-1), corresponding to intraconfigurational
      transitions between the 1T2g lowest excited electronic state and the Gamma1,
      Gamma4, and Gamma5/Gamma3 spinor levels of the 3T1g ground state, respectively.
      The octahedral OsF6(2-) chromophore does not emit from higher excited states, in
      contrast to related chloride and bromide host lattices, where several excited
      states show luminescence. The highly resolved single-crystal luminescence and
      absorption spectra are rationalized with ligand field parameters 10 Dq = 24570
      cm(-1), B = 500 cm(-1), C = 2380 cm(-1), zeta = 3000 cm(-1). Transition
      intensities reveal an intermediate coupling situation for OsF6(2-): Whereas they
      generally follow the selection rules derived in the L-S coupling scheme,
      additional information can be gained from the j-j coupling limit. The resolved
      vibronic structure allows the identification of the most efficient ungerade
      parity enabling modes (vibronic origins) and shows that progressions along the
      a1g, e(g), and t2g modes occur for some transitions.

PMID- 11442367
TI  - Structure-property relationships of a tetrapyrrolidinyl PNP-lariat ether and its
      complexes with potassium, sodium, and silver cations.
AB  - Spectral properties of the tetrapyrrolidinyl PNP-lariat ether, L, and its
      complexes with K+, Na+, and Ag+ were investigated. Crystal structures of L and
      its complex with potassium iodide [KL]I were determined. Protonation constants of
      the ligand and formation constants of its complexes with Ag+, K+, and Na+ in
      aqueous solutions were determined. 1H NMR, 31P NMR, FTIR, and ESIMS spectra as
      well as potentiometric measurements indicate that complexation of Ag+ involves
      participation of the polyether oxygen donors and the endocyclic nitrogen atom of
      the cyclophosphazene ring. On the other hand, for complexation of K+ and Na+,
      only polyether oxygen atoms are involved. The latter conclusion is confirmed in
      the solid-state structure of the [KL]I complex.

PMID- 11442368
TI  - pH-dependent investigations of vanadium(V)-peroxo-malate complexes from aqueous
      solutions. In search of biologically relevant vanadium(V)-peroxo species.
AB  - The established biochemical potential of vanadium has spurred considerable
      research interest in our lab, with specific focus on pertinent synthetic studies
      of vanadium(III) with a biologically relevant, organic, dicarboxylic acid, malic
      acid, in aqueous solutions. Simple reactions between VCl3 and malic acid in
      water, at different pH values, in the presence of H2O2, led to the crystalline
      dimeric complexes (Cat)4[VO(O2)(C4H3O5)]2*nH2O (Cat = K+, n = 4, 1; Cat = NH4+, n
      = 3, 2) and K2[VO(O2)(C4H4O5)]2*2H2O (3). All three complexes were characterized
      by elemental analysis, FT-IR, and UV/visible spectroscopies. Compound 1
      crystallizes in the monoclinic space group P2(1)/c, with a = 8.380(5) A, b =
      9.252(5) A, c = 13.714(8) A, beta = 93.60(2) degrees, V = 1061(1) A3, and Z = 4.
      Compound 2 crystallizes in the triclinic space group P1, with a = 9.158(4) A, b =
      9.669(4) A, c = 14.185(6) A, alpha = 104.81(1) degrees, beta = 90.31(1) degrees,
      gamma = 115.643(13) degrees, V = 1085.0(7) A(3), and Z = 2. Compound 3
      crystallizes in the monoclinic space group P2(1)/c, with a = 9.123(8) A, b =
      9.439(8) A, c = 10.640(9) A, beta = 104.58(3) degrees, V = 887(1) A3, and Z = 2.
      The X-ray structures showed that, in 1 and 2, the dimers consist of two
      (V(V)=O)2O2 rhombic units to which two malate ligands are attached. The ligands
      are triply deprotonated and, as such, they coordinate to vanadium(V), promoting a
      pentagonal bipyramidal geometry. In 3, the dimeric (V(V)=O)2O2 rhombic unit
      persists, with the two doubly deprotonated malate ligands coordinated to the
      vanadium(V) ions. UV/vis and EPR spectroscopic studies on the intermediate blue
      solutions of the synthesis reactions of 1-3 support the existence of vanadyl
      containing dimeric species. These species further react with H2O2 to yield
      oxidation of V(IV)2O2 to V(V)2O2 and coordination of the peroxide to vanadium(V).
      From the collective data on 1-3, it appears that pH acts as a decisive factor in
      dictating the structural features of the isolated complexes. The details of the
      introduced structural differentiation in the reported complexes, and their
      potential relevance to vanadium(V) dicarboxylate systems in biological media are
      dwelled on.

PMID- 11442369
TI  - Structural and conformational properties of 2-propynylphosphine
      (propargylphosphine) as studied by microwave spectroscopy supplemented by quantum
      chemical calculations.
AB  - The microwave spectrum of 2-propynylphosphine (propargylphosphine), H-C triple
      bond C-CH2-PH2, has been investigated in the 18-26.5 and 32-48 GHz spectral
      regions at about -50 degrees C. Two conformers with different orientation of the
      phosphino group, denoted conformer I and conformer II, respectively, were
      assigned. Conformer I has a symmetry plane (Cs symmetry) with both hydrogen atoms
      of the phosphino group pointing toward the triple bond (C-C-P-H dihedral angles
      approximately 47 degrees from syn-periplanar (0 degrees )). The C-C-P-H dihedral
      angles are 73 and 167 degrees, respectively, from syn-periplanar in conformer II.
      Only one of the hydrogen atoms of the phosphino group points toward the triple
      bond in this rotamer. Conformer I is 1.5(20) kJ/mol more stable than II. The
      dipole moment of II was determined to be (in units of 10(-30) C m) mu(a) = 0
      (assumed), mu(b) = 3.05(7), mu(c) = 1.60(9), and mu(tot) = 3.44(9) [mu(tot) =
      1.03(3) D]. Two vibrationally excited states were assigned for each of the two
      rotamers I and II. Their frequencies were determined by relative intensity
      measurements. Many of the transitions of conformer II were split into two
      components presumably because of tunneling of the phosphino group. The tunneling
      frequency was determined to be 0.814(42) MHz for the ground vibrational state and
      11.49(18) MHz for the first excited state of the C-P torsional vibration. Quantum
      chemical calculations at the B3LYP and MP2 levels of theory using the 6
      311++G(3df,2pd) basis set reproduced experimental rotational constants, quartic
      centrifugal distortion constants, and dipole moment components within a few
      percent. The energy difference between the two conformers was calculated using
      the Gaussian-2 theory, and conformer I was found to be more stable than conformer
      II by 2.1 kJ/mol.

PMID- 11442370
TI  - Vanadium, molybdenum, and sodium triethanolamine complexes derived from an
      assembly system containing tetrathiometalate and triethanolamine.
AB  - The reaction system composed of triethanolamine (TEA) and tetrathiovanadate in
      the presence of MeONa (MeOLi) or NaNH2 was studied to afford vanadium and alkali
      metal TEA complexes. Complexes [M subsetV6O6[N(CH2CH2O)2(CH2CH2OH)]6]2S6 (M = Na
      (1), Li (2)) contain two cyclic V((IV)) [12]metallacrown-6 cations linked by a
      polysulfide S6(2-) anion. Also separated from the reaction system is a novel
      sodium TEA complex [[Na(TEA)]2S6]n (3), in which parallel coordination chains
      [Na(TEA)+]n are connected by O-H...S hydrogen bonds forming 3-D network
      structure. Variable-temperature conductance of 3 was determined to display
      semiconductor feature. The desulfurization of VS4(3-) was observed to form S6(2-)
      anion and/or S8 molecule in the synthetic reactions of 1-3. A striking contrast
      was noted that MoS4(2-) did not desulfurize in the similar reaction to that of
      VS4(3-) with TEA, and a Na/TEA complex containing MoS4(2-), (Et4N)2[Na2(mu
      TEA)2(CH3OH)2](MoS4)2 (4), was obtained instead. The S...H-O and O...H-O hydrogen
      bonds play an important role in forming the one- or three-dimensional structures
      for all these complexes by the linkages between clusters and chains. The IR
      spectrum indicates the structural similarity of complexes 1 and 2. For complex 4,
      the Mo=S stretch vibration at 468 cm(-1) showing widening and slight red-shift
      and the slight movement of the 1H NMR signals of TEA ligand to downfield are
      considered to be the influence of the S...H-O hydrogen bonds. Variable
      temperature magnetic susceptibility data were collected for complex 1. The effect
      magnetic moment per V6 unit varies gradually from 4.04 muB at 300 K to 6.24 muB
      at 5 K, exhibiting ferromagnetic interaction. Heisenberg-type vector-coupling
      model and molecular field approximation were used to treat the interaction
      between the paramagnetic sites and gave a good fitting result: J = 3.97 cm(-1),
      J' = 1.99 cm(-1), g = 1.99, F = 3.64 x 10(-3). Density functional calculation was
      also performed to complex 1 and its Li, K analogues. The lowest total bonding
      energy of -874.001 eV was obtained for [Na subsetV6(mu3-O)6] complex containing
      six unpaired electrons, indicating the stability of a V6 system with six
      independent spins S = 1/2. When the alkali metal ion is inserted into the [V6(mu3
      O)6] cavity, the positive values of the bonding interaction (E(b)) indicate that
      the insertion depresses the total energy and that complexes 1 and 2 together with
      K+ complex may exist. However, the lowest E(b) value of the K+ complex implies
      its instability.

PMID- 11442371
TI  - Lanthanide chemistry with (bis[[bis(carboxymethyl)amino]methyl]phosphinate: what
      does an extra phosphinate group do to EDTA?
AB  - H5XT (bis[[bis(carboxymethyl)amino]methyl]phosphinic acid) is an EDTA(4-)-like
      ligand containing an extra phosphinate group. [Co(II)(XT)]3-, [Co(III)(XT)]2-,
      and a series of [Ln(XT)]2- complexes have been prepared. The phosphinate group is
      not coordinated in the Co complexes but is bound in the lanthanide complexes.
      Solid state and solution behaviors of Ln-XT species are consistent: both
      monoprotonated and nonprotonated species have been found. Protonation of the
      metal complex does not lead to dissociation of a carboxylate; rather, the proton
      distributes around the molecular ion. The pM values of Ln-XT are comparable to
      those of Ln-EDTA but are higher than those of Ln-TMDTA. The inclusion of a
      phosphinate eases the selectivity of an EDTA-type ligand for late lanthanides.

PMID- 11442372
TI  - Tetranuclear mixed-metal M(II)2Cu(II)2 complexes derived from a phenol-based
      macrocyclic ligand having two N(amine)2O2 and two N(imine)2O2 metal-binding
      sites.
AB  - The reaction of N,N'-dimethyl-N,N'-ethylenebis(5-bromo-3-formyl-2
      hydroxybenzylaminato)copper(II) with ethylenediamine in aqueous DMF with excess
      perchloric acid resulted in the [2:2] cyclic condensation of the constituents,
      providing the dinuclear Cu(II) complex [Cu2(H2R)](ClO4)2. It crystallizes in the
      monoclinic space group P2(1)/c, with a = 19.603(3) A, b = 13.370(2) A, c =
      21.072(3) A, beta = 98.87(1) degrees, V = 5456(1) A3, and Z = 4. The ligand R4-
      has two N(amine)2O2 and two N(imine)2O2 metal-binding sites sharing two phenolic
      oxygens, and [Cu2(H2R)](ClO4)2 has the two Cu(II) ions in the N(imine)2O2 sites
      and two protons in the N(amine)2O2 sites. [Cu2(H2R)](ClO4)2 was converted by
      neutralization into [Cu2(R)], from which mixed-metal Cu(II)2M(II)2 complexes
      [Cu2M2(R)Cl4] (M = Co(II), Ni(II), Zn(II)) were derived.
      [Cu2Co2(R)Cl4]*2CHCl3*H2O crystallizes in the monoclinic space group C2/c, with a
      = 32.514(3) A, b = 12.246(3) A, c = 19.827(2) A, beta = 126.082(1) degrees, V =
      6380(1) A3, and Z = 4. [Cu2Zn2(R)Cl4]*2CHCl3*H2O crystallizes in the monoclinic
      space group C2/c, with a = 32.53(1) A, b = 12.242(2) A, c = 19.729(9) A, beta =
      126.03(3) degrees, V = 6354(4) A3, and Z = 4. The two complexes are isotructural
      and have a dimer-of-dimers structure with two separated Cu(II)M(II) units. In
      each dinuclear unit, the Cu(II) is bound to the N(imine)2O2 site and the M(II) is
      bonded to a phenolic oxygen and two nitrogens of the N(amine)2O2 site. The Cu(II)
      and M(II) ions are bridged by a phenolic oxygen and an exogenous chloride ion.
      The Cu(II)2Ni(II)2 complex has a defect double-cubane structure. Cryomagnetic
      studies for the Cu(II)2Co(II)2 complex indicate an antiferromagnetic spin
      exchange interaction within each dinuclear Cu(II)Co(II) unit (J = -9.5 cm(-1)
      based on H = -2JS(Cu)S(Co)). The Cu(II)2Ni(II)2 complex shows a weak
      antiferromagnetic interaction between the adjacent Cu(II) and Ni(II) ions (-3.5
      cm(-1)) and a weak ferromagnetic interaction between the two Ni(II) ions (+2.0
      cm(-1)).

PMID- 11442373
TI  - Solid-state coordination chemistry: structural influences of copper
      phenanthroline subunits on oxovanadium organophosphonate phases. hydrothermal
      synthesis and structural characterization of the two-dimensional materials
      [Cu(phen)(VO)(O3PCH2PO3)(H2O)], [[Cu(phen)]2(V2O5)(O3PCH2CH2PO3)], and
      [[Cu(phen)]2(V3O5)(O3PCH2CH2CH2PO3)2(H2O)] and the three-dimensional phase
      [[Cu(phen)]2(V3O5)(O3PCH2PO3)2(H2O)].
AB  - The hydrothermal reactions of CuCl2*2H2O, Na3VO4, 1,10-phenanthroline, and the
      appropriate organodiphosphonate ligand yield [Cu(phen)(VO)(O3PCH2PO3)(H2O)] (1),
      [[Cu(phen)]2(V2O5)(O3PCH2CH2PO3)] (2), [[Cu(phen)]2(V3O5)(O3PCH2CH2CH2PO3)2
      (H2O)] (3), and [[Cu(phen)]2(V3O5)(O3PCH2PO3)2(H2O)] (4). Compounds 1-3 exhibit
      two-dimensional structures. The structures exhibit distinct vanadium building
      blocks: square pyramidal, mononuclear V(IV) sites in 1, a binuclear unit of
      corner-sharing V(V) tetrahedra in 2, and a trinuclear unit of corner-sharing V(V)
      square pyramids and a V(IV) octahedron in 3. The network structures of 1 and 2
      are constructed from one-dimensional oxovanadium-diphosphonate chains linked by
      Cu(II) square pyramids into two-dimensional layers. In contrast, compound 3
      exhibits a two-dimensional oxovanadium-organodiphosphonate network, with Cu(II)
      sites decorating the surfaces. Compound 4 is unique in exhibiting a framework
      structure, which may be described as a three-dimensional oxovanadium
      organodiphosphonate substructure with [Cu(phen)]2+ subunits covalently attached
      to the surface of channels running parallel to the a-axis. The magnetic
      properties of 1-4 are also correlated to the structural characteristics. The
      magnetic behavior of 2 is thus dominated by antiferromagnetic interactions. The
      magnetic behavior of 1 and 4 is consistent with the presence of two distinct
      paramagnetic metal ions, Cu(II) and V(IV). In contrast, 3 does not exhibit
      ferrimagnetic behavior, but rather weak antiferromagnetic coupling. Crystal data:
      1, C13H10N2CuP2VO8, monoclinic P2(1)/c, a = 9.0656(5) A, b = 8.6584(5) A, c =
      20.934(1) A, beta = 97.306(1) degrees, Z = 4; 2, C26H20N4Cu2P2V2O11, triclinic
      P1, a = 10.6096(5) A, b = 11.6951(5) A, c = 13.1796(6) A, alpha = 71.369(1)
      degrees, beta = 70.790(1) degrees, gamma = 80.738(1) degrees, Z = 2; 3,
      C30H28N4Cu2P4V3O18, triclinic P1, a = 9.4356(6) A, b = 10.6556(6) A, c =
      11.0354(7) A, alpha = 118.187(1) degrees, beta = 91.416(1) degrees, gamma =
      107.821(1) degrees, Z = 1; 4, C26H20N4Cu2P4V3O18, monoclinic, P2(1)/c a =
      8.3947(3) A, b = 16.8401(7) A, c = 11.9144(5) A, beta = 93.903(1) degrees, Z = 2.

PMID- 11442374
TI  - Olefin epoxidation by molybdenum and rhenium peroxo and hydroperoxo compounds: a
      density functional study of energetics and mechanisms.
AB  - A density functional study on olefin epoxidation by rhenium and molybdenum peroxo
      complexes has been carried out. Various intermediates and transition structures
      of the systems CH3ReO3/H2O2, H3NMoO3/H2O2, and H3NOMoO3/H2O2 were characterized,
      including ligated and unligated mono- and bisperoxo intermediates as well as
      hydroperoxo derivatives. For the rhenium system the bisperoxo complex
      CH3ReO(O2)2*H2O was found to be most stable and the one with the lowest
      transition state for epoxidation of ethylene (activation barrier of 16.2
      kcal/mol), in line with experimental findings. However, participation of
      monoperoxo and hydroperoxo complexes in olefin epoxidation cannot be excluded.
      For both molybdenum systems, hydroperoxo species with an additional ammonia model
      ligand in axial position were calculated to be most stable. Inspection of
      calculated activation barriers of ethylene epoxidation reveals that, in both
      molybdenum systems, hydroperoxo mechanisms are competitive if not superior to
      peroxo mechanisms. The reaction barriers of the various oxygen transfer processes
      can be rationalized by structural, orbital, and charge characteristics,
      exploiting a model that interprets the electrophilic nature of the reactive
      oxygen center.

PMID- 11442375
TI  - Halogenodisilanes: precursors for new disilane derivatives.
AB  - Starting from hexachloro- or hexabromodisilane a wide variety of 1,2
      disubstituted tetrachlorodisilanes (RSiCl2SiCl2R) [R = Cp (2a), 4-iPrC6H4(SiMe3)N
      (2b), 2,6-iPr2C6H3(SiMe3)N (2c), (Me3Si)2CH (2d) (Me3Si)3C (2e), (Me3Si)3Si
      (2f)], tetrabromodisilanes (RSiBr2SiBr2R) [R = Cp (3a), 4-iPrC6H4(SiMe3)N (3b),
      (Me3Si)3Si (3f)] and the monosubstituted pentahalogenodisilanes CpSiX2SiX3 [X =
      Cl (4), Br (5)] were prepared. The tetrachlorodisilanes 2a-e are converted to
      various functionalized disilanes. Ammonolysis of 2a-e leads to the
      tetraaminodisilanes [RSi(NH2)2Si(NH2)2R] 6a-e. A reduction of 2d with LiAlH4
      resulted in the formation of the disilane RSiH2SiH2R [R = (Me3Si)2CH] 7 and the
      metathesis with Me3SnF yielded the tetrafluorodisilane RSiF2SiF2R [R =
      (Me3Si)2CH] 8. Treatment of 6d with reagents containing H acidic protons (HX) [X
      = Br, I and OH] leads under elimination of NH3 to the tetrabromo- R2SiBr2SiBr2R
      (3d) tetraiodo- RSiI2SiI2R (9) and the tetrahydroxodisilane RSi(OH)2Si(OH)2R (10)
      [R = (Me3Si)2CH]. Single-crystal X-ray structural analysis of 2d, 6a, 6d, and 9
      are reported.

PMID- 11442376
TI  - Pentacoordinate cobalt(III) thiolate and nitrosyl tropocoronand compounds.
AB  - Reaction of [Co(TC-n,m)]+ with (Me4N)(SC6F5), where (TC-n,m) is a tropocoronand
      with n and m linker chain methylene groups, yielded the thiolate complexes
      [Co(SC6F5)(TC-3,3)] (1a), and [Co(SC6F5)(TC-4,4)] (2a), which were structurally
      characterized. Use of more electron-releasing thiolates afforded the [Co(TC-n,m)]
      reduction product and the corresponding disulfide. The bent nitrosyl complexes
      [Co(NO)(TC-3,3)] (1b) and [Co(NO)(TC-4,4)] (2b) were synthesized from [Co(TC
      n,m)] and NO and their structures were also determined. Compounds 1a and 1b have
      square-pyramidal geometry like all other structurally characterized [MX(TC-3,3)]
      complexes. Compounds 2a and 2b have trigonal-bipyramidal stereochemistry,
      formerly rare for Co(III). Although 1a, 1b, and 2a are paramagnetic, 2b is
      diamagnetic due to the strong antibonding pi-interaction between the metal and NO
      pi* orbitals. In the presence of excess NO, [Co(TC-4,4)] exhibited novel
      reactivity in which a putative Co(N2) adduct formed.

PMID- 11442377
TI  - A unique framework in BaGa2Sb2: a new Zintl phase with large tunnels.
AB  - BaGa2Sb2 was obtained from a direct element combination reaction in a sealed
      graphite tube at 950 degrees C, and its structure was determined by single
      crystal X-ray diffraction methods. It crystallizes in the orthorhombic space
      group Pnma (No. 62) with a = 25.454(5) A, b = 4.4421(9) A, c = 10.273(6) A, and Z
      = 8. The anionic [Ga2Sb6/3]2- framework is assembled by the ethane-like dimeric
      [Sb3Ga-GaSb3] units sharing Sb atoms, forming parallel tunnels with a 26-membered
      ring cross section. These tunnels are filled with Ba atoms. The three-dimensional
      [Ga2Sb6/3]2- framework features a new structure type. The compound satisfies the
      classical Zintl concept. Band structure calculations indicate that the material
      is a semiconductor, and this is confirmed by spectroscopic experiments which show
      E(g) approximately 0.35 eV. The calculations also suggest that the structure is
      stabilized by strong Ga-Ga covalent bonding interactions. Polycrystalline ingots
      of BaGa2Sb2 show room-temperature electrical conductivity of approximately 65
      S/cm and a Seebeck coefficient of +65 muV/K.

PMID- 11442378
TI  - Phosphodiester hydrolysis by lanthanide complexes of bis-tris propane.
AB  - Potentiometric titrations of the mixtures of lanthanide(III) perchlorates and bis
      Tris propane (BTP) reveal formation of dinuclear hydroxo complexes
      M2(BTP)2(OH)n(6-n), where M = La(III), Pr(III), Nd(III), Eu(III), Gd(III), and
      Dy(III) and n = 2, 4, 5, or 6, in the pH range 7-9. ESI-MS data confirm the
      presence of dinuclear species. Kinetics of the hydrolysis of bis(4-nitrophenyl)
      phosphate (BNPP), mono-4-nitrophenyl phosphate (NPP), and 4-nitrophenyl acetate
      (NPA) in the lanthanide(III)-BTP systems has been studied at 25 degrees C in the
      pH range 7-9. The second-order rate constants for the hydrolysis of BNPP by
      individual lanthanide hydroxo complexes have been estimated by using the multiple
      regression on observed rate constants obtained at variable pH. For a given metal,
      the rate constants increase with increasing in the number n of coordinated
      hydroxide ions. In a series of complexes with a given n, the second-order rate
      constants decrease in the order La > Pr > Nd > Eu > Gd > Dy. Hydrolysis of NPP
      follows Michaelis-Menten-type "saturation" kinetics. This difference in kinetic
      behavior can be attributed to stronger binding of NPP dianion than BNPP monoanion
      to the lanthanide(III) species. Activities of lanthanide complexes in the
      hydrolysis of NPA, which is 10(6) times more reactive than BNPP in alkaline or
      aqueous hydrolysis, are similar to those in BNPP hydrolysis indicating unique
      capability of lanthanide(III) cations to stabilize the transition state of
      phosphate diester hydrolysis. Results of this study are analyzed together with
      literature data for other metal cations in terms of the Bronsted correlation and
      transition state-catalyst complexation strength.

PMID- 11442379
TI  - Enhanced second harmonic generation on passing from a mono- to a dicopper(II)
      bis(salicylaldiminato) schiff base complex.
AB  - A new ligand (H2LOH) obtained from the Schiff base condensation of 4
      (diethylamino)salicylaldehyde with 1,3-diamino-2-propanol is reported, which
      yields two different copper(II) complexes: CuLOH and Cu2LO(AcO). Crystal data are
      as follows. CuLOH*EtOH: monoclinic, P2(1)/n, a = 17.810(2) A, b = 8.515(1) A, c =
      18.912(2) A, beta = 112.72(1) degrees, Z = 4. Cu2LO(AcO)*1/2H2O: monoclinic,
      P2(1)/c, a = 21.407(4) A, b = 15.308(2) A, c = 20.156(3) A, beta = 116.83(2)
      degrees, Z = 4. Cu2LO(AcO)*1/2H2O is antiferromagnetically coupled with J = 
      207.7 cm(-1) (J being the parameter of the exchange Hamiltonian H = -J
      S(A).S(B)). CuLOH and Cu2LO(AcO) exhibit good transparencies in the visible
      frequency range with absorption maxima at 353 and 372 nm, respectively. An
      enhancement of 83% of the quadratic hyperpolarizability (beta) is observed by the
      electric field induced second harmonic (EFISH) technique on passing from the mono
      to the dinuclear species. Qualitative ZINDO/SCI quantum-chemical predictions
      give a satisfactory account for this enhancement. The spin dependence of the NLO
      response of Cu2LO(AcO)*1/2H2O is found to be negligible within the framework of
      the DFT theory.

PMID- 11442380
TI  - Heat capacity of the spin crossover complex [Fe(2-pic)3]Cl2*MeOH: a spin
      crossover phenomenon with weak cooperativity in the solid state.
AB  - Heat capacities of the spin crossover complex [Fe(2-pic)3]Cl(2)*MeOH (2-pic: 2
      picolylamine or 2-aminomethylpyridine) were measured with an adiabatic
      calorimeter between 12 and 355 K. A broad heat capacity peak, starting from
      approximately 80 K, culminating at approximately 150 K, and terminating at
      approximately 250 K, was observed. The temperature range of the heat capacity
      anomaly corresponds to that where the low-spin and high-spin states coexist in
      the 57Fe Mossbauer spectra. The enthalpy and entropy changes arising from the
      heat capacity anomaly were 8.88 kJ x mol(-1) and 59.5 J x K(-1) x mol(-1),
      respectively. The entropy gain was much larger than the contribution expected
      from the change in the spin-manifold R ln 5 (13.4 J x K(-1) x mol(-1)) where R is
      the gas constant. The remaining entropy gain is attributed to the contribution
      from the change in the internal vibrations. On the basis of the domain model, the
      number of molecules per domain was found to be very close to unity, implying a
      very weak cooperativity in the spin crossover occurring in the solid state of
      this complex.

PMID- 11442381
TI  - Control of the stereochemical impact of the lone pair in lead(II)
      tris(pyrazolyl)methane complexes. Improved preparation of Na[B[3,5-(CF3)2C6H3]4].
AB  - The reaction of Pb(acac)2 with 2 equiv of [H(Et2O)2][B[3,5-(CF3)2C6H3]4]
      (HBAr(f)) in CH2Cl2 followed by addition of 2 equiv of either HC(pz)3 or HC(3,5
      Me2pz)3 (pz = pyrazolyl ring) leads to the formation of [Pb[HC(pz)3]2][B[3,5
      (CF3)2C6H3]4]2 (1) and [Pb[HC(3,5-Me2pz)3]2][B[3,5-(CF3)2C6H3]4]2 (2),
      respectively. The cation in 1 has a distorted octahedral structure with a
      stereochemically active lone pair on lead(II). In contrast, the cation in 2 is
      trigonally distorted octahedral with the lone pair on the lead(II) clearly
      stereochemically inactive. The driving force for this cation to have a
      stereochemically inactive lone pair is that in this geometric arrangement the
      interligand distances between adjacent 3-position methyl groups are close to 4.0
      A, the sum of the van der Waals radii of two methyl groups. To facilitate this
      chemistry, the synthesis of Na[B[3,5-(CF3)2C6H3]4], needed to prepare HBAr(f),
      has been dramatically improved. The main change is to add NaBF4 to the reaction
      mixture before forming the Grignard from the reaction of magnesium and 3,5
      (CF3)2C6H3Br. The Grignard reacts with the NaBF4 as it forms, reducing the danger
      of explosion and leading to a higher isolated yield of the product.
      Crystallographic information: 1 is triclinic, P1, a = 13.0133(6) A, b =
      17.2210(7) A, c = 24.7634(11) A, alpha = 71.7300(10) degrees, beta = 82.3630(10)
      degrees, gamma = 70.5120(10) degrees, Z = 2; 2 is triclinic, P1, a = 12.756(4) A,
      b = 13.469(4) A, c = 17.160(5) A, alpha = 82.454(7) degrees, beta = 89.904(8)
      degrees, gamma = 72.995(7) degrees, Z = 1.

PMID- 11442382
TI  - Electrochemical synthesis, X-ray single crystal, IR spectroscopic, and quantum
      chemical investigation of molybdenum and tungsten hexamethoxides.
AB  - The anodic oxidation of molybdenum metal in MeOH at both low anodic and cathodic
      current density (0.025 A/cm2) and electrolyte temperatures kept below 20 degrees
      C provides an efficient approach to Mo(OMe)6 (I). W(OMe)6 (II) can be obtained
      from the electrolytes, prepared via anodic dissolution of tungsten, by fractional
      crystallization. The symmetrically independent units in the structures of I and
      II, being isomorphous, follow the C1 (slightly distorted D2d) symmetry.
      Theoretical calculations performed for a free molecule of I indicate that this
      low symmetry may be the result of the packing of the molecules in the crystal
      structure and also an inherent property imposed by the bonding in this compound.
      Crystal data for I: Mo(OMe)6 at 22 degrees C, a = 7.0976(13), b = 6.6103(12), and
      c = 12.286(2) A, beta = 90.068(3) degrees, V = 576.41(18) A3, monoclinic P2/n, Z
      = 2. Crystal data for II: W(OMe)6 at 22 degrees C, a = 7.1164(19), b =
      6.6414(18), and c = 12.304(3) A, beta = 90.047(5) degrees, V = 581.5(3) A3,
      monoclinic P2/n, Z = 2.

PMID- 11442383
TI  - Entropy-controlled solvolytic dissociation kinetics of lanthanide(III) complexes
      with polyaminocarboxylates in aqueous solutions.
AB  - The factors involved in the formation of an inert complex in terms of solvolysis
      reaction have been studied for lanthanide(III)-acyclic polyaminocarboxylate
      complexes, as the basis for kinetically controlled selectivity used in analytical
      methodologies such as HPLC and HPCE. The rate constants for solvolysis and acid
      assisted dissociation processes of the lanthanide complexes were determined in a
      batch system through metal- and ligand-exchange reactions. The reagents used were
      8-amino-2-[(2-amino-5-methylphenoxy)methyl]-6-methoxyquinoline-N,N,N',N'
      tetraacetic acid (Quin2) and O,O'-bis(2-aminophenyl)ethylene glycol-N,N,N',N'
      tetraacetic acid (BAPTA) as octadentate ligands and trans-1,2-diaminocyclohexane
      N,N,N',N'-tetraacetic acid (CyDTA) as a hexadentate ligand. It has been found
      that the rate constants for solvolysis vary from 5.7 x 10(-3) x s(-1) (La3+) to
      1.7 x 10(-6) x s(-1) (Lu3+) depending on the ionic radii of Ln(III) ions for the
      Quin2 complexes, while no such monotonic dependence was observed for the BAPTA
      complexes. Among the parameters of activation, it is worth noting that there is a
      considerably large negative entropy of activation, of up to -250 J x mol(-1) x K(
      1), and it is this which is responsible for the inertness of the Ln
      polyaminocarboxylate complexes. Our data suggest that multiple ligation of the
      ligand in favor of the large coordination number of Ln(III) ions is of key
      importance for formation of the negative entropy of activation, in addition to
      the basicity of the ligand which also plays a significant role in the slow
      dissociation kinetics of the Ln(III) complexes.

PMID- 11442384
TI  - Synthesis and characterization of cyclopentadienyl titanium(aryloxide)sulfide
      complexes.

PMID- 11442385
TI  - Contrasting formation of a (phenylthio)phosphinimine and (phenylthio)phosphazide.
      Synthesis of metal complexes.

PMID- 11442386
TI  - The synthesis and conformation of sterically congested seven-membered rings
      containing tetracoordinate germanium(IV): determination of the DeltaG* for ring
      inversion.

PMID- 11442387
TI  - Synthesis of a diindacycle by transmetalation of 1,8
      bis(trimethylstannyl)naphthalene with InCl3.

PMID- 11442388
TI  - Simple glucal-based linker for the immobilization of alcohols on solid support.

PMID- 11442389
TI  - Solid-phase directed ortho-lithiation and the preparation of a phthalide library.
AB  - An efficient solid-phase synthesis of phthalides is described in which aromatic
      carboxylic acids or acid chlorides and ketones are used as building blocks. The
      carboxylic acid or acid chloride is tethered to aminomethylated polystyrene
      resin, forming a secondary amide, which functions as both the linker and the
      directing metalation group. This allows the resin-bound benzamides to be ortho
      lithiated at 0 degrees C. The ortho-lithiated species can be quenched with
      benzaldehydes, benzophenones, and even acetophenones, affording resin-bound
      alcohols. A cyclative cleavage is induced by simply warming the resin in toluene
      or dioxane, yielding the desired phthalide compounds in exceptionally high
      purity.

PMID- 11442390
TI  - Polymer-supported benzotriazoles as catalysts in the synthesis of
      tetrahydroquinolines by condensation of aldehydes with aromatic amines.
AB  - Four polymer-supported benzotriazoles were prepared by linkage of 5
      (hydroxymethyl)benzotriazole and benzotrizaole-5-carboxylic acid with Wang resin,
      Merrifield resin, and (monomethoxy)poly(ethylene glycol). The solid-phase and
      liquid-phase syntheses of tetrahydroquinolines were achieved by two-pair coupling
      reactions of aldehydes and aromatic amines using these polymer-supported
      benzotriazoles as the promoters. The ether-type benzotriazole prepared by loading
      5-(hydroxymethyl)benzotriazole onto Merrifield resin turned out to be the
      catalyst of choice. Thus, a series of tetrahydroquinoline products were obtained
      in high purity by simple filtration, and the resin was recovered for reuse
      without loss of activity.

PMID- 11442391
TI  - Parallel synthesis and biocatalytic amplification of a cross-conjugated
      cyclopentenone library.
AB  - A combination of parallel chemical synthesis and biocatalysis has been used to
      prepare and amplify a library of cross-conjugated cyclopentenones. A number of
      marine and terrestrial natural products with antibiotic activity are known to
      incorporate this pharmacophore. The library was screened for anticancer,
      antimycobacterial, antifungal, and antibacterial activity. The positive results
      from the screens provide an indication of the structural features that are
      associated with activity in the various assays and suggest promising avenues for
      further inquiry.

PMID- 11442392
TI  - Solid-supported benzotriazoles. 2. Synthetic auxiliaries and traceless linkers
      for the combinatorial synthesis of unsymmetrical ureas.
AB  - Resin-bound benzotriazole chemistry applied to the solid-phase synthesis of
      arrays of unsymmetrical aryl ureas is described here. The chemistry assessment
      process, the monomer rehearsal, the preparation of a discrete library by
      automated parallel synthesis, the parallel purification protocol employing solid
      phase scavenging, and the complete analytical characterization of the library
      components are also presented.

PMID- 11442393
TI  - Solid-phase synthesis of benzoxazoles from 3-nitrotyrosine.
AB  - A method to synthesize benzoxazoles on solid phase using 3-nitrotyrosine as a
      scaffold has been developed. The synthesis couples N-protected 3-nitrotyrosine to
      polystyrene via a Wang-type linker. The polymer-supported 3-nitrotyrosine is
      deprotected and the resultant primary amine converted to a tertiary amine via
      sequential reductive alkylation using aromatic followed by unhindered aliphatic
      aldehydes. The phenol is acylated, and the nitro group is reduced using SnCl(2).
      The resulting amino ester is then dehydratively cyclized to a benzoxazole. The
      synthesis was developed for a large mix and split (50 x 50 x 50) combinatorial
      library. The single compounds presented herein represent a diverse array of the
      types of monomers amenable to the chemistry developed.

PMID- 11442394
TI  - Solid-phase library synthesis of alkoxyprolines.
AB  - The library synthesis of alkoxyprolines was achieved using an acid-stable,
      nucleophile-cleavable solid support. A hydroxythiophenol linker derived from
      Merrifield resin was esterified with the corresponding ethers of BOC
      hydroxyproline. Removal of the BOC protecting group with trifluoroacetic acid
      followed by acylation gave solid-supported hydroxyproline derivatives. Cleavage
      from the solid support with excess primary amines or excess secondary amines
      followed by purification of the crude products from the excess amine by supported
      liquid-liquid extraction gave the alkoxyproline library in high purity.

PMID- 11442395
TI  - Monitored selection of DNA-hybrids forming duplexes with capped terminal C:G base
      pairs.
AB  - Reported here are the results of a search for modified oligodeoxynucleotides with
      a 5'-terminal cytidine residue whose affinity for target strands is enhanced by
      5'-acylamido groups. These acylamido groups were envisioned to act as molecular
      caps that bind to the exposed terminal base pair of the duplex with the target
      strand. A total of 52 capped oligonucleotides of the sequence R-CGGTTGAC, where R
      denotes the 5'-appendage and C a 5'-amino-2',5'-dideoxycytidine residue, were
      tested. Among the building blocks employed to modify the 5'-amino group of the
      DNA strand were carboxylic acid residues, either appended directly or via an
      amino acid residue, and aromatic aldehydes, coupled via reductive amination. The
      carboxylic acids employed ranged from Fmoc-glycine to (Fmoc)(2)-vancomycin and
      included a number of aromatic acids and bile acids. Small libraries were
      subjected to MALDI-monitored nuclease selection experiments, and selected
      compounds were tested in UV-melting assays with target strands. Cholic acid
      appendages stabilized terminal C:G base pairs to the greatest extent, with
      melting point increases of up to 10 degrees C. Further, the cholic acid residue
      enhanced base pairing fidelity at the terminus, as determined in melting analyses
      with target strands containing a mismatched nucleobase at the 3'-terminus.

PMID- 11442396
TI  - Solid-phase development of a L-hydroxybenzotriazole linker for heterocycle
      synthesis using analytical constructs.
AB  - The development of a 1-hydroxybenzotriazole linker for the synthesis of
      heterocyclic derivatives is described, utilizing analytical construct methodology
      to facilitate the analysis of resin samples. A UV-chromophore-containing
      analytical construct enabled the accurate determination of resin loading and the
      automated monitoring of key reactions using only small quantities of resin. The
      syntheses of an array of isoxazole derivatives are reported.

PMID- 11442397
TI  - Development and application of a carbonyl-(13)C-enriched backbone amide linker
      for solid-phase reaction monitoring.
AB  - The synthesis and application of a carbonyl-(13)C backbone amide linker are
      described. The labeled unit is conveniently mixed with commercial resins,
      providing a rapid means of monitoring chemistry performed with this linker on
      solid support using conventional (13)C NMR methods.

PMID- 11442398
TI  - Solid-phase synthesis of peptidomimetic inhibitors for the hepatitis C virus NS3
      protease.
AB  - The NS3 serine protease enzyme of the hepatitis C virus (HCV) is essential for
      viral replication. Short peptides mimicking the N-terminal substrate cleavage
      products of the NS3 protease are known to act as weak inhibitors of the enzyme
      and have been used as templates for the design of peptidomimetic inhibitors.
      Automated solid-phase synthesis of a small library of compounds based on such a
      peptidomimetic scaffold has led to the identification of potent and highly
      selective inhibitors of the NS3 protease enzyme.

PMID- 11442399
TI  - Bis-8-hydroxyquinoline-armed diazatrithia-15-crown-5 and diazatrithia-16-crown-5
      ligands: possible fluorophoric metal ion sensors.
AB  - The synthesis and preliminary photophysical properties of a series of
      diazatrithia-15-crown-5 and diazatrithia-16-crown-5 ligands containing two 8
      hydroxyquinoline sidearms are reported. The ligands were prepared by a two-step
      process. First, diazatrithiacrown ethers 11 and 12 were prepared by treating
      bis(alpha-chloroamide) 5 with various dimercaptans followed by reduction using a
      boron-THF complex. Hydroxymethyl-substituted macrocycle 12 was rearranged to
      hydroxy-substituted diazatrithia-16-crown-5 in refluxing aqueous HCl. Macrocyclic
      diamines 11-13 were converted to either 5-chloro-8-hydroxyquinolin-7-ylmethyl
      substituted diazatrithiacrown ethers 14-16 by a Mannich aminomethylation reaction
      or to 8-hydroxyquinolin-2-ylmethyl-substituted diazatrithiacrown ethers 17-19 by
      reductive amination using 8-hydroxyquinoline-2-carboxaldehyde. Preliminary
      photophysical studies show that ligands 16 and 19 exhibit increased fluorescence
      in the presence of Zn(2+), indicating that these ligands could be chemical
      sensors for Zn(2+).

PMID- 11442400
TI  - Solvent-free asymmetric aminoalkylation of electron-rich aromatic compounds:
      stereoselective synthesis of aminoalkylnaphthols by crystallization-induced
      asymmetric transformation.
AB  - Electron-rich aromatic compounds such as 2-naphthol give a faster and asymmetric
      1-aminoalkylation with high yields when treated with (R)-1-phenylethylamine and
      aromatic aldehydes in solvent-free conditions. An asymmetric transformation of a
      second kind, probably induced by the preferential crystallization of one
      diastereomer, affords the straightforward and stereoselective synthesis of
      aminoalkylnaphthols. Mechanisms predictable for this asymmetric reaction are
      reported. The absolute configurations and the conformations of the unknown
      aminonaphthols are widely ascertained.

PMID- 11442401
TI  - Catalytic asymmetric synthesis of macrocyclic (E)-allylic alcohols from omega
      alkynals via intramolecular 1-alkenylzinc/aldehyde additions.
AB  - The omega-alkynals yielded macrocyclic (S)-allylic alcohols in a one-pot reaction
      sequence involving alkyne monohydroboration, boron to zinc transmetalation, and
      ((+)-DAIB)-catalyzed enantioselective intramolecular ring closure to the aldehyde
      function. A general study of this macrocyclization methodology is presented with
      respect to ligand type, size, and nature of the formed rings.

PMID- 11442402
TI  - Stereocontrolled formation of epoxy peroxide functionality appended to a lactam
      ring.
AB  - The action of tert-butyl hydroperoxide and tin(IV) chloride upon allylic alcohols
      containing a lactam ring leads mainly to epoxy alkyl peroxides with high
      diastereoselection. Both the stereochemistry and the products formed are in
      marked contrast to the reactions of the analogous carbocyclic allylic alcohols
      with tert-butyl hydroperoxide-VO(acac)2.

PMID- 11442403
TI  - Synthesis and unusual chemical reactivity of certain novel 4,5-disubstituted 7
      benzylpyrrolo[2,3-d][1,2,3]triazines.
AB  - The fact that only two pyrrolo[2,3-d][1,2,3]triazines heterocycles had been
      reported in the literature prompted us to initiate studies designed to provide
      additional members of this ring system. Initial attempts to prepare additional
      derivatives of the 7-unsubstituted pyrrolo[2,3-d][1,2,3]triazin-4-ones were
      limited by their low chemical reactivity. Subsequently, 7-benzyl-5
      carboxamidopyrrolo[2,3-d][1,2,3]triazin-4-one (16) was prepared from diethyl 2
      nitropyrrole-3,4,-dicarboxylate via an alkylation, ammonolysis, reduction and
      intramolecular diazocoupling sequence. Conversion of 16 into 7-benzyl-4-(1,2,4
      triazol-1-yl)pyrrolo[2,3-d][1,2,3]triazine-5-carbonitrile (17) was accomplished,
      and nucleophilic displacements of the 4-triazol-1-yl group were studied.
      Treatment of 17 with NH3/CH3CN gave a mixture of 4-amino-7-benzylpyrrolo[2,3
      d][1,2,3]triazine-5-carbonitrile (19) and 2-amino-1-benzylpyrrole-3,4
      dicarbonitrile (21). A mechanism to account for the formation of this mixture is
      described along with studies on the effect that ammonia concentration and a TFA
      catalyst have on the product ratio. Compound 19 was converted into the 5
      carboxamide and 5-thioamide derivatives of 19.

PMID- 11442404
TI  - Dimetalation of pyrazines. a one-pot synthesis of multisubstituted pyrazine C
      nucleosides.
AB  - As a part of our efforts to pursue direct, convergent, and concise methodologies
      for the synthesis of pyrazine C-nucleosides, we have successfully established a
      sequential dilithiation-addition method, which allows one to introduce two
      different functional groups to a pyrazine ring in a one-pot fashion. 2,6
      Dichloropyrazine was dilithiated at -100 degrees C and then allowed to react with
      an electrophile, such as bromine, iodine, or disulfides, followed by a reaction
      with a protected ribonolactone to afford C-nucleosides. After reduction and
      deprotection, tetrasubstituted pyrazine C-nucleosides, including 2,6-dichloro-3
      iodo-5-(beta-D-ribofuranosyl)pyrazine and 2-bromo-3,5-dichloro-6-(beta-D
      ribofuranosyl)pyrazine, were obtained. A tandem reaction sequence occurred when
      disulfides were used, resulting in the formation of 5,6-bis-methylthio-2-chloro-3
      (beta-D-ribofuranosyl)pyrazine and 6-(beta-D-ribofuranosyl)-2,3,5-tris
      phenylthiopyrazine.

PMID- 11442405
TI  - Stereoisomeric sugar-derived indolizines as versatile building blocks: synthesis
      of enantiopure di- and tetrahydroxyindolizidines.
AB  - The synthesis of the sugar-derived (1S,2R,8aR)-1,2-di-O-isopropylidene
      1,2,3,5,6,8a-hexahydro-5-oxoindolizine (8) and by analogy of the corresponding
      stereoisomers ent-8 and ent-7, an epimer at C2 of ent-8, has been accomplished in
      a straightforward manner. The carbon-carbon double bond and the carbonyl
      functionalities on the six-membered ring make these nitrogen-containing
      heterocycles useful building blocks for the efficient preparation of a variety of
      enantiopure polyhydroxylated indolizidines of interest for their glycosidase
      inhibitory activity. We report here the synthesis of 2,8a-diepilentiginosine 12
      from 8 and the preparation of stereoisomeric 1,2,7,8-tetrahydroxyindolizidines 9
      11 performed by OsO4-catalyzed double bond syn dihydroxylation of 7 and 8,
      followed by deoxygenation of the amide group.

PMID- 11442406
TI  - Molecular addition compounds. 18. Borane adducts with hydroxydialkyl sulfide
      borates for hydroboration. New, essentially odorless, water-soluble sulfide
      borane acceptors for hydroboration.
AB  - Hydroxydialkyl sulfides of general formula RS(CH2CH2)nH (R = Et, t-Bu, i-Am; n =
      1-3) and thiodiethanol monomethyl ether (9) have been synthesized and used as
      borane carriers. The compounds 3 and 6 (R = Et, n = 2, 3), 7 (R = t-Bu, n = 3),
      and 9 are completely miscible with water and exhibit only very mild odor. The
      sulfides were transformed into the corresponding borates by treatment either with
      boric acid or with diborane. The borates complex 3 mol of borane per 1 mol of
      borate to give highly reactive, stable, liquid adducts, hydroborating 1-octene in
      15 min at room temperature. The adducts derived from water soluble sulfides 3 and
      9, selected for the hydroboration of more hindered olefins, reacted readily with
      (-)-beta-pinene, 1-methylcyclohexene, and 2,3-dimethyl-2-butene. The carrier
      borates liberated from the adducts during hydroboration are readily hydrolyzed to
      give 3 and 9, which can be washed off with water from trialkylboranes or
      oxidation products. Consequently, hydroxydialkyl sulfides 3 and 9 are the first
      completely water-soluble sulfide borane carriers that can be washed off in the
      workup of hydroboration products. The adducts derived from 3 and 9 are new,
      highly promising reagents suitable for large scale hydroborations and reductions.

PMID- 11442407
TI  - Synthesis of a polymerizable metal-ion-chelating lipid for fluid bilayers.
AB  - Hydrated lipid structures, such as liposomes, that display tethered metal-ion
      chelating groups have proven useful in peptide and protein binding, as well as 2D
      protein crystallization through molecular recognition of accessible histidine
      sites in proteins and peptides. Polymerizable metal-ion-chelating lipids bearing
      a reactive diacetylene group have been described. These interesting compounds can
      be polymerized in the solid-analogous phase. Here we describe the design of the
      first polymerizable metal-ion-chelating lipid that can be used in the fluid,
      i.e., liquid analogous, phase of lipid bilayers. The synthesis of 1-palmitoyl-2
      [8-[(E,E)-2',4'-hexadienoyloxy]octanoyl]-sn-glycero-3-N-[11-[N',N'
      bis[carboxymethyl]imino]-3,6,9-trioxaundecanoyl] phosphatidylethanolamine (1) is
      described. The chelator moiety, iminodiacetate (IDA), was linked to the
      polymerizable phosphatidylethanolamine (PE) with a terminal 2,4-hexadienoyl
      (sorbyl) group through an oligo(ethylene glycol)-based spacer. Lipid 1-Cu complex
      is designed to be combined with the corresponding polymerizable matrix lipids
      (bis-SorbPC) to form functionalized liposomes that can be stabilized by various
      polymerization methods.

PMID- 11442408
TI  - Structures of cordypyridones A-D, antimalarial N-hydroxy- and N-methoxy-2
      pyridones from the insect pathogenic fungus Cordyceps nipponica.
AB  - Bioassay-guided fractionation of the extracts from the insect pathogenic fungus
      Cordyceps nipponica BCC 1389 led to the isolation of N-hydroxy- and N-methoxy-2
      pyridones, cordypyridones A-D (1-4). Structures of these compounds, including
      absolute configuration, were determined by spectroscopic methods, chemical
      conversions and single-crystal X-ray diffraction analyses. Codypyridones A and B,
      atropisomers of each other, exhibited potent in vitro antimalarial activity with
      IC(50) values of 0.066 and 0.037 microg/mL, respectively, while their
      cytotoxicity was much weaker.

PMID- 11442409
TI  - Synthesis of enantiomerically and diastereomerically pure 2(S)-amino-6(R)-hydroxy
      1,7-heptanedioic acid dimethyl ester hydrochloride from cycloheptadiene.
AB  - The complete carbon framework of enantiomerically and diastereomerically pure
      2(S)-amino-6(R)-hydroxy-1,7-heptanedioic acid dimethyl ester hydrochloride was
      derived from cycloheptadiene in six steps utilizing an amino acid-derived
      acylnitroso Diels-Alder reaction as the key step. This versatile amino diester
      has been previously used to synthesize amino-differentiated diaminopimelic acid
      (DAP) and biologically active analogues. In addition, after formation of a novel
      aminoxy diketopiperazine, the newly formed carboxyl groups were differentiated by
      a novel transpeptidation of the amino acid that directed the stereochemistry of
      the initial cycloaddition.

PMID- 11442410
TI  - Ruthenium-catalyzed oxidative cleavage of olefins to aldehydes.
AB  - Three oxidation protocols have been developed to cleave olefins to carbonyl
      compounds with ruthenium trichloride as catalyst (3.5 mol %). These methods
      convert olefins that are not fully substituted to aldehydes rather than
      carboxylic acids. While aryl olefins were cleaved to aromatic aldehydes in
      excellent yields by using the system of RuCl3-Oxone-NaHCO3 in CH3CN-H2O (1.5:1),
      aliphatic olefins were converted into alkyl aldehydes with RuCl3-NaIO4 in 1,2
      dichloroethane-H2O (1:1) in good to excellent yields. It is noteworthy that
      terminal aliphatic olefins were cleaved to the corresponding aldehydes in
      excellent yields by using RuCl3-NaIO4 in CH3CN-H2O (6:1).

PMID- 11442411
TI  - Determination of absolute configuration of acyclic 1,2-diols with Mo2(OAc)4. 1.
      Snatzke's method revisited.
AB  - The method employing dimolybdenum tetraacetate for the assignment of the absolute
      configuration of optically active 1,2-diols is thoroughly revisited and applied
      to several compounds, some of which were synthesized by asymmetric cis
      dihydroxylation. No exceptions were found to the empirical rule relating the sign
      of the induced CD spectrum and the configuration of the substrate, whatever its
      structure and sterical requirements. To broaden the scope of the method, its
      applicability to critical situations commonly encountered with synthetic products
      is tested. It is demonstrated that the method can be applied on samples with low
      chemical and optical purity, and that it may lend itself as a means to estimate
      the ee. The roles of the water content of the sample and of the diol-to
      dimolybdenum ratio are investigated.

PMID- 11442412
TI  - Reactivity of stable trifluoroacetaldehyde hemiaminals. 1. An unexpected reaction
      with enolizable carbonyl compounds.
AB  - In the presence of enolizable carbonyl compounds, hemiaminals of fluoral and
      related polyfluoroaldehydes behave as equivalents of fluoroalkyl iminium
      compounds and provide beta-polyfluoroalkyl beta-dialkylamino ketones, which are
      easily transformed, under acidic conditions, into beta-polyfluoroalkylenones.

PMID- 11442413
TI  - Total synthesis of (+/-)-scopadulin.
AB  - The first total synthesis of (+/-)-scopadulin, an aphidicolane diterpene, is
      described. The core structure (A/B/C/D ring system) was constructed by an initial
      synthesis of the B/C/D ring system by our reported methods and a subsequent A
      ring cyclization by intramolecular aldol condensation. A highly stereoselective
      cyanation of the tetracyclic enone by Et2AlCN gave a trans-fused A/B ring system
      with a beta-cyanide at C-4. Stereoselective construction of a quaternary carbon
      at C-4 was achieved by alpha-alkylation of the cyano group and conversion of the
      sterically hindered cyano group to a methyl group via our novel reaction for
      conversion of primary aliphatic amines into alcohols. Finally, the total
      synthesis of (+/-)-scopadulin was accomplished by a highly chemo- and
      stereoselective methylation at C-16 and modification of the C-4 alpha
      functionality. The stereoselectivity observed in the MeTi(O-i-Pr)3-mediated
      methylation for the generation of a tertiary axial alcohol at C-16 is extremely
      high.

PMID- 11442414
TI  - Synthesis of (+)-juruenolide c: use of sequential 5-exo-digonal radical
      cyclization, 1,5-intramolecular hydrogen transfer, and 5-endo-trigonal
      cyclization.
AB  - Acetylenic alcohol 10 was converted successively into silane 11 and phenylseleno
      carbonate 14. On treatment with Ph3SnH, the latter underwent 5-exo-digonal
      radical cyclization, intramolecular hydrogen transfer, and 5-endo-trigonal
      cyclization, yielding 15. Conversion of the lactone into the lactol benzyl ether
      17, carbon-silicon bond cleavage, and regeneration of the lactone carbonyl gave
      (+)-juruenolide C (1).

PMID- 11442415
TI  - beta-Sulfinyl alpha,beta-unsaturated carbonyl compounds from enantiomerically
      pure sulfenic acids.
AB  - The addition of enantiopure sulfenic acids to oxoalkynes constitutes a new and
      efficient methodology for the synthesis of beta-sulfinyl alpha,beta-unsaturated
      carbonyl compounds. Sulfenic acids 3 and 4 were generated by thermolysis of
      suitable precursors and trapped in situ by oxoalkynes 5, affording (R(S),E)- and
      (S(S),E)-3-alkylsulfinyl-1-phenyl-2-propen-1-ones, 4-alkylsulfinyl-3-buten-2
      ones, and 3-[(1S)-isoborneol-10-sulfinyl]-2-propenoates 6 and 7 in good yields
      and in enantiomerically pure form after simple column chromatography. (R(S),E)-3
      [(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen-1-one (6(R)a) was involved as a
      heterodiene in inverse-electron-demanding Diels-Alder reactions with readily
      available electron-rich dienophiles 14 and 15, corroborating in each case the
      sulfinyl auxiliary capability in controlling the stereochemical outcome of these
      cycloadditions. Furthermore, the addition of methylmagnesium iodide to the
      carbonyl moiety of 6(R)a demonstrated that the chiral sulfur atom exerts a remote
      stereocontrol in this reaction if assisted by the hydroxy group being part of the
      isoborneol substituent.

PMID- 11442416
TI  - Stereocontrolled syntheses of carbocyclic C-nucleosides and related compounds.
AB  - Carbocyclic 9-deazapurine nucleosides (1-4), a spiranic pyrimidone carbocyclic
      compound (5), and an unusual carbocyclic isonucleoside (6) were prepared as
      enantiomerically pure compounds via the key intermediates 10 and 21 from 1,4
      gamma-ribonolactone. The key intermediate 10 was prepared by stereoselective
      reduction with Bu3SnH and then converted to carbocyclic C-ribonucleosides 1, 3,
      and 4. 2',3'-Didehydro-2',3'-dideoxycarbocyclic 9-deazainosine (2) was prepared
      from a 2',3'-dimesylate 17 by treatment with Li2Te followed by an acidic
      deprotection. The key bicyclic intermediate 21 was prepared from a diol 20 by an
      intramolecular cyclization using CHI3-Ph3P-imidazole and converted to the
      spiranic compound 5 and an olefinic nucleoside 6 by the construction of the
      heterocyclic moiety followed by deprotection.

PMID- 11442417
TI  - Solvent effect on the alpha-effect for the reactions of aryl acetates with butane
      2,3-dione monoximate and p-chlorophenoxide in MeCN-H2O mixtures.
AB  - Second-order rate constants have been measured spectrophotometrically for the
      nucleophilic reactions of three substituted phenyl acetates with butane-2,3-dione
      monoximate (Ox(-)) as an alpha-nucleophile and p-chlorophenoxide (ClPhO(-)) as
      corresponding normal nucleophile, in MeCN-H2O mixtures of varying compositions at
      25.0 +/- 0.1 degrees C. The reactivity of Ox(-) toward the aryl acetates
      decreases upon addition of MeCN to the reaction medium up to ca. 30 mol % MeCN,
      followed by a gradual increase in rate upon further addition of MeCN. A similar
      result has been obtained for the reaction of ClPhO(-) with the aryl acetates.
      However, the decrease in rate is more significant for the less reactive ClPhO(-)
      than for the more reactive Ox(-). Thus, for all the aryl acetates studied, Ox(-)
      exhibits a sizable alpha-effect (k(Ox)-/k(ClPhO)-) whose magnitude increases as
      the mol % MeCN in the reaction medium increases. The relative basicities
      (DeltapK(a)) of Ox(-) and ClPhO(-) have been determined spectrophotometrically
      using piperazine as a reference base. The DeltapK(a) values increase on
      increasing the mol % MeCN in the medium for both Ox(-) and ClPhO(-). The
      difference in the relative basicities of these nucleophiles (DeltaDeltapK(a))
      becomes larger with increasing mol % MeCN. The plots of log k(Ox)-/k(ClPhO)- vs
      DeltaDeltapK(a) for the three substrates are linear with near-unit slope,
      indicating that the difference in the relative basicity of the nucleophiles is
      largely responsible for the increasing alpha-effect with medium composition in
      this system.

PMID- 11442418
TI  - Enantioselective synthesis for the (-)-antipode of the pyrazinone marine
      alkaloid, hamacanthin A.
AB  - A short enantioselective total synthesis for the (-)-antipode of the antifungal
      marine alkaloid, hamacanthin A, (6R)-3,6-bis(6-bromoindol-3-yl)-5,6-dihydro-2(1H)
      pyrazinone, is described. This synthesis proceeds through the coupling of 3
      indolyl-alpha-oxoacetyl chloride and 3-indolyl azidoethylamine, followed by
      intramolecular aza-Wittig type cyclization. A concise and useful approach for the
      synthesis of (1R)-1-(indol-3-yl)-2-azidoethylamine using the Sharpless asymmetric
      dihydroxylation reaction followed by stereospecific azidation is also presented.

PMID- 11442419
TI  - Stereoselective hydroformylation: key step for the assembly of polypropionate
      subunits.
AB  - An anti-selective hydroformylation of 2-propylidene-substituted 1,3-dioxanes 16,
      17, and 26 with excellent levels of acyclic stereocontrol has been achieved. The
      basis of this result was a careful substrate design making use of a syn-pentane
      interaction as the decisive stereochemical control element. Confirmation of this
      working hypothesis came from conformational analysis studies on alkenic substrate
      16 employing 2D NOESY experiments in solution and MACROMODEL/MM3 calculations.
      This stereoselective, transition metal-catalyzed, C-C bond-forming reaction could
      serve as a key step for the construction of the all-anti and syn-anti stereotriad
      building blocks 20, 21, and 31, which should be well-suited for target-oriented
      polypropionate synthesis. Application of this methodology for the construction of
      a C5-C11 building block for the synthesis of bafilomycin A1 is described.

PMID- 11442420
TI  - Synthesis of a bicyclic analogue of AZT restricted in an unusual O4'-endo
      conformation.
AB  - The [3.2.0]bicyclic beta-nucleoside analogue 5 has been designed as a
      conformationally restricted analogue of the anti-HIV drug AZT. The synthesis of 5
      as well as its alpha-anomer 29 is hereby described. The synthesis was
      accomplished from D-arabinose via a modified Corey-Link procedure
      stereoselectively incorporating the azide moiety as well as a methyl ester
      function. When the tert-butyldiphenylsilyl group was used as a permanent
      protecting group, a selective formation of an oxetane ring failed. When using the
      p-methoxyphenyl group as a permanent protecting group, 5 and 29 were efficiently
      obtained via a selective reduction of the ester, a nucleobase coupling followed
      by separation of the anomers and ring-closing procedures. The nucleoside 5 is
      conformationally restricted in an unusual O4'-endo (East) conformation, which is
      an intermediate between the North- and South-type conformations. Nevertheless,
      neither 5 nor 29 displayed any anti-HIV activity.

PMID- 11442421
TI  - Nucleophilic substitution and Claisen rearrangement reactions of model
      fluoroalkenes of general structure R-CF=CF-CF3.
AB  - Fluoroalkenes of general structure R-CF=CF-CF3 (2a, R = cyclopentyl and 2b, R =
      cyclohexyl), prepared in high yield in two steps from hexafluoropropene and the
      appropriate cycloalkane, react with oxygen, carbon, and hydrogen nucleophiles to
      give R-CX=CF-CF3 derivatives (X = H, OR, R, Ar). Reaction of fluoroalkenes 2a and
      2b with allylic alkoxides gave products arising from Claisen rearrangement,
      providing access to keto-alkenes bearing >CFCF3 units in mid-aliphatic chain
      positions.

PMID- 11442422
TI  - Synthesis of 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine as
      potential in vivo precursors of fluorinated norepinephrines.
AB  - The title compounds were prepared by the aldol condensation of 3,4-dibenzyloxy-2
      fluorobenzaldehyde and 4,5-dibenzyloxy-2-fluorobenzaldehyde with the
      oxazolidinone 2, a chiral glycine equivalent. Removal of the chiral auxiliary and
      blocking groups produced the target amino acids 2-fluoro- and 6-fluoro-(2S,3R)
      (3,4-dihydroxyphenyl)serine (1b and 1c) in >98% ee.

PMID- 11442423
TI  - Selective oxidation of a keramaphidin B model.
AB  - A crucial step in the Baldwin and Whitehead proposal for explaining the
      biogenesis of the marine alkaloid manzamine A is the selective oxidation of
      natural keramaphidin B to an iminium salt 3, which is then hydrolyzed to give the
      aldehyde 4. Conditions are now presented in which this selective oxidation can be
      performed on model compound 8, leading to the iminium salt 16. Although this salt
      can be considered as a model equivalent of the proposed aldehyde intermediate 4,
      it was found to be very resistant to hydrolysis as was the corresponding amide
      20. From a synthetic point of view, the reported results illustrate the
      usefulness of the temporary protection of tertiary amines as aminoborane
      derivatives and constitute a good method for the oxidation of a sterically
      hindered tertiary nitrogen atom in the presence of a second nitrogen.

PMID- 11442424
TI  - Stereoselective synthesis of 2-alkenylaziridines and 2-alkenylazetidines by
      palladium-catalyzed intramolecular amination of alpha- and beta-amino allenes.
AB  - Whereas palladium-catalyzed reaction of N-arylsulfonyl-alpha-amino allenes with
      an aryl iodide (4 equiv) in the presence of potassium carbonate (4 equiv) in DMF
      at around 70 degrees C affords the corresponding 3-pyrroline derivatives, the
      reaction in refluxing 1,4-dioxane under otherwise identical conditions yields
      exclusively or most predominantly the corresponding 2-alkenylaziridines bearing
      an aryl group on the double bond. Similarly, N-arylsulfonyl-beta-amino allenes
      can be also cyclized into the corresponding alkenylazetidines bearing a 2,4-cis
      configuration under palladium-catalyzed cyclization conditions in DMF.

PMID- 11442425
TI  - Novel versatile fullerene synthons.
AB  - We report the synthesis of three novel, versatile fullerene intermediates whose
      main feature is the presence of an amino end group. Simple condensation reactions
      of these intermediates under standard conditions produce new derivatives that are
      useful for applications in materials science and medicinal chemistry.

PMID- 11442426
TI  - Intermolecular metallo-ene reaction catalyzed by palladium.

PMID- 11442427
TI  - Solution synthesis and characterization of aza-beta(3)-peptides (N(alpha)
      substituted hydrazino acetic acid oligomers).

PMID- 11442428
TI  - Supramolecular structures by recognition and self-assembly of complementary
      partners: an unprecedented ionic hydrogen-bonded triple-stranded helicate.

PMID- 11442429
TI  - General stereoselective synthesis of chemically differentiated alpha-diamino
      acids: synthesis of 2,6-diaminopimelic and 2,7-diaminosuberic acids.

PMID- 11442430
TI  - A convenient synthesis of the novel hypoglycemic agent SDZ PGU 693.

PMID- 11442431
TI  - A highly diastereoselective synthesis of new polyhydroxy 2
      aminonorbornanecarboxylic acids.

PMID- 11442432
TI  - High-yield double cyclopropanation of benzene.

PMID- 11442433
TI  - Template effects in the self-assembly of a [2]rotaxane and a [2]pseudorotaxane
      with the same binding sites in the linear component.

PMID- 11442434
TI  - Recent reviews. 61.
AB  - Reviews are listed in order of appearance in the sources indicated. In
      multidisciplinary review journals, only those reviews which fall within the scope
      of this Journal are included. Sources are listed alphabetically in three
      categories: regularly issued review journals and series volumes, contributed
      volumes, and other monographs. Titles are numbered serially, and these numbers
      are used for reference in the index. Major English-language sources of critical
      reviews are covered. Encyclopedic treatises, annual surveys such as Specialist
      Periodical Reports, and compilations of symposia proceedings are omitted. This
      installment of Recent Reviews covers principally the early part of the 2001
      literature. Previous installment: J. Org. Chem. 2001, 66(7), 2538-46.

PMID- 11442435
TI  - Abnormal signals on proton density-weighted MRI of the superior cerebellar
      peduncle in progressive supranuclear palsy.
AB  - OBJECTIVE: To assess MRI signal abnormalities of the superior cerebellar peduncle
      (SCP) in progressive supranuclear palsy (PSP) patients. MATERIAL AND METHODS:
      Signal changes were examined on proton density-weighted images (PDWI) and on T2
      weighted images (T2WI) of SCP in 9 PSP patients, and findings were compared to
      those in 20 Parkinson's disease patients and 20 age-matched control subjects.
      RESULTS: We observed effacement or lack of clarity of the low signal on PDWI in
      SCP in 4 of 9 PSP patients, but not in any of the Parkinson's disease patients or
      control subjects. These signal changes were not observed on T2WI. CONCLUSIONS:
      The signal changes on PDWI may be a specific finding reflecting demyelination and
      gliosis of SCP in PSP. Our findings suggest that evaluation of SCP on PDWI may be
      helpful in the diagnosis of PSP patients.

PMID- 11442436
TI  - Antiepileptic drug utilization: a Danish prescription database analysis.
AB  - OBJECTIVES: The purpose of the study was to use prescription data from a Danish
      database to analyse and evaluate antiepileptic drug (AED) utilization, and
      compare with other prevalence studies. METHODS: A Danish research database
      covering outpatient prescription data from a population of 471,873 persons was
      used. Prescription records on all patients prescribed AEDs during 1998 were
      retrieved. A cohort was extracted from the group of AED users. RESULTS: We
      identified 5426 AED users. A total of 3756 of the 5426 AED users were included in
      our cohort. Of the subjects in the cohort 74% were on monotherapy, 19% used two
      AEDs and only 7% used three or more AEDs. The eight most frequent regimens were
      all monotherapy: carbamazepine, oxcarbazepine, phenobarbital, valproic acid,
      lamotrigine, clonazepam, phenytoin and primidon in that order. The estimated
      crude 1-year prevalence of AED use was 0.77% for women and 0.83% for men
      (P<0.001), and it increased with age for both genders. CONCLUSIONS: The
      prescription pattern reported here is in accordance with the general guidelines
      for the treatment of epilepsy in Denmark, except for a surprisingly extensive use
      of phenobarbital. With specific reservations the figures appear to be reasonable
      estimates of the prevalence of epilepsy.

PMID- 11442437
TI  - Juvenile myoclonic epilepsy--an experience from north western India.
AB  - OBJECTIVES: The clinical data on cases of Juvenile Myoclonic Epilepsy (JME) were
      analysed. Response to initial small dosages (lower than usual) of sodium
      valproate and further lower maintenance dosages in patients who were seizure free
      for 2 years on drug were assessed. MATERIAL AND METHODS: Seventy-six patients who
      were diagnosed to have Juvenile Myoclonic Epilepsy on definite criteria were
      studied. All patients were put on sodium valproate in dosages (lower than usual)
      for initial control and further lower maintenance dosage and response evaluated.
      RESULTS: The clinical profile was found to be similar as in other parts of India.
      There was a female preponderance and average delay of 4.9 years in final
      diagnosis. Forty-eight (63.1%) patients showed good control on 15 mg/kg/day
      dosages of sodium valproate. After a seizure free interval of 2 years, 58% of
      patients could be maintained on small dosages ranging from 3-5 mg/kg/day to 6-8
      mg/kg/day. CONCLUSION: The majority of JME patients responded well not only to
      sodium valproate in dosages lower than usually prescribed but required very small
      dosages for maintenance after a seizure free period of 2 years.

PMID- 11442438
TI  - Butyrylcholinesterase in lumbar and ventricular cerebrospinal fluid.
AB  - OBJECTIVES: This study establishes reference data for human lumbar CSF
      butyrylcholinesterase (E.C.3.1.1.8.) activity and investigates the enzyme
      activity in ventricular CSF. We comment on the relationship between CSF
      butyrylcholinesterase activity and other laboratory parameters. SUBJECTS AND
      METHODS: We investigated 64 lumbar CSF samples obtained from a clinically healthy
      population and 169 ventricular CSF samples collected from 90 neurosurgical
      patients. RESULTS: The reference range we recommend for lumbar CSF
      butyrylcholinesterase activity is 5.4 to 17.0 nmol/min x ml. The majority of
      ventricular butyrylcholinesterase activities in our patient subset ranged up to 5
      nmol/min x ml. CONCLUSIONS: We established the relative influence of serum and
      CNS components on total CSF butyrylcholinesterase activity. The CNS fraction
      predominates the total butyrylcholinesterase activity in normal lumbar CSF. In
      ventricular CSF enzyme influx from serum outweighs the CNS component.

PMID- 11442439
TI  - Correlations of brain MRI parameters to disability in multiple sclerosis.
AB  - OBJECTIVES: The objective was to correlate magnetic resonance imaging (MRI) T2
      weighted lesion load and measures of white matter atrophy in the brain to
      disability in a population-based sample of patients with multiple sclerosis (MS).
      MATERIAL AND METHODS: A well defined cohort of patients was drawn at random from
      the general MS population by using the Danish Multiple Sclerosis Registry. A semi
      automated local thresholding technique was used to quantify T2-weighted lesions
      on MRI; whereas manual tracing was applied to measure the corpus callosum brain
      ratio (CCR) and the ventricle brain ratio (VBR). RESULTS: A sample of 86 patients
      with a mean age of 43.3 years (SD 4.3), mean disease duration of 13.6 years (SD
      4.4) and a median Expanded Disability Status Score (EDSS) of 6.0 was identified.
      The correlation between total lesion area of the brain (TLA) and disability
      (EDSS) for the whole sample was moderate (Spearman rank correlation coefficient
      r=0.48, P<0.001). Also correlations of CCR and VBR to disability (r=0.32-0.46)
      were significant. CONCLUSIONS: Correlations of TLA and disability in this study
      were rather strong. Hence, T2-weighted MRI lesion load in the brain still plays
      an important role as a surrogate marker of disease and as a secondary outcome
      measure in phase III treatment trials.

PMID- 11442440
TI  - Visually evoked potentials in respiratory chain disorders.
AB  - OBJECTIVES: Little is known about the frequency of abnormal visually evoked
      potentials (VEPs) in patients with respiratory chain disorders (RCDs). We thus
      wanted to investigate the frequency of abnormal VEPs in RCDs, how often VEPs are
      abnormal despite normal visual acuity, and which of the VEP variables are most
      often abnormal. MATERIAL AND METHODS: Reversal checkerboard VEPs of 26 patients
      with RCDs, aged 32-74 years, were evaluated. RESULTS: VEPs were abnormal in 17 of
      the 26 cases (65%). The P100 latency was prolonged at least unilaterally in 16
      patients. The P100/N145 amplitude was decreased in a single patient. VEPs were
      abnormal without visual impairment in 9 cases (53%). CONCLUSION: VEPs prove
      useful to detect clinical or subclinical impairment of the optical tract in
      patients with RCDs. In the majority of the cases, the P100 latencies are
      prolonged while the P100/N145 amplitude remains normal.

PMID- 11442441
TI  - Altered inhibition of motor responses in Tourette Syndrome and Obsessive
      Compulsive Disorder.
AB  - OBJECTIVES: The Gilles de la Tourette Syndrome (TS) and Obsessive Compulsive
      Disorder (OCD) have been shown to display impaired cognitive and motor
      inhibition. This study investigated inhibitory mechanisms of motor responses in
      order to expand the understanding of sensorimotor integration processes in both
      disorders. We hypothesized that both patient groups would display altered frontal
      inhibitory activity. MATERIAL AND METHODS: To this end event-related brain
      potentials (ERPs) were recorded in a STOP-paradigm in groups of TS and OCD
      patients and in a control group. The paradigm required the execution of a motor
      response after a "go" signal was given and the occasional suppression of this
      response after a second "stop" signal occurred. RESULTS: Behavioral parameters
      and Lateralized Readiness Potential (LRP) confirmed that both patient groups were
      well able to initiate motor responses. "Go" and "stop" stimuli elicited an
      enhanced frontal negative activity in both patient groups. In addition, "stop"
      stimuli were associated with a frontal shift of the NoGo-Anteriorization (NGA) in
      the TS group but not in the OCD group. CONCLUSIONS: The data are interpreted to
      indicate altered frontal inhibitory functions. Similarities and dissimilarities
      between the findings for TS and OCD are discussed with respect to other
      pathophysiologic aspects of the disorders.

PMID- 11442442
TI  - Clinical trial of acetazolamide in SCA6, with assessment using the Ataxia Rating
      Scale and body stabilometry.
AB  - OBJECTIVE: To investigate the effect of acetazolamide on spinocerebellar ataxia
      type 6 (SCA6). METHODS: Acetazolamide (250-500 mg/day) was administered orally
      for 88 weeks to 6 patients with SCA6, and its effect was quantitatively monitored
      using the Ataxia Rating Scale (ARS) and body sway analysis by stabilometry.
      RESULTS: During administration of acetazolamide, the ARS score and the amplitude
      of body sway were significantly reduced compared with before administration.
      However, the response became weaker after 1 year of treatment. CONCLUSION:
      Although this was an open trial, the results suggested that acetazolamide can
      temporarily reduce the severity of symptoms during the progression of SCA6.

PMID- 11442443
TI  - Repeated thalamic haemorrhage: case report and review of the literature.
AB  - Recurrence of thalamic haemorrhage has rarely been reported. A 70-year-old woman
      had recurrent thalamic haemorrhage five-times during a period of 6 years. The
      first, second and fifth haemorrhages were located in the right thalamic region,
      and the third and fourth haemorrhages in the left thalamic region. Cranial
      computed tomography and magnetic resonance imaging revealed no abnormal lesion.
      After the first, second, and third haemorrhage with medical treatments, the
      patient recovered her functional ability or was at least capable of self-care at
      home. However, after the fourth and fifth haemorrhage, with medical therapy the
      patient's prognosis was severe disability. In this case, systemic blood pressure
      was normalized without antihypertensive agents after the first attack. However,
      there was an episode of sudden hypertension at each attack. Although the
      mechanism of rebleeding has not been clarified, rebleeding might be associated
      with changes of cerebral circulation following the previous haemorrhage.

PMID- 11442444
TI  - Autonomic dysfunction associated with multiple pelvic ganglioneuromas.
AB  - We describe the case of a 59-year-old male in which several symptoms of autonomic
      dysfunction resulted associated with the presence of multiple ganglioneuromas in
      the adrenal glands and in paravertebral spaces. In a 2-year period, the patient
      developed sexual dysfunctions, micturitional disturbances and severe orthostatic
      hypotension and was erroneously diagnosed as having primary autonomic failure.
      However, the examination of all the autonomic functions showed that papillary
      function and cardiovascular reflexes were normal. CT scan of the abdomen revealed
      the presence of several small masses in the adrenal glands and along the lumbar
      sympathetic chain. Cytologic examination of the adrenal glands showed clusters of
      ganglionlike cells interspersed with Schwann cells, leading to the diagnosis of
      ganglioneuromas. Patients with signs and symptoms of autonomic dysfunction need
      an extensive clinical and laboratory examination of all the autonomic functions
      in order to exclude secondary causes of the symptomatology.

PMID- 11442445
TI  - Overlapping Guillain-Barre syndrome and Bickerstaff's brainstem encephalitis
      associated with anti-GQ1b IgG antibody after herpes simplex virus infection.
AB  - Herpes simplex virus (HSV) is a rare, antecedent infectious agent in Guillain
      Barre syndrome (GBS). We report a patient with overlapping GBS and Bickerstaff's
      brainstem encephalitis (BBE). The patient had a vesicular lesion on her nose.
      Antecedent HSV type 1 (HSV-1) infection was confirmed by isolation of the virus
      and detection of the presence of serum anti-HSV-1 IgM antibody during the acute
      phase. Her serum IgG had high anti-GQ1b antibody titer. External ophthalmoplegia
      has been noted in 2 of 4 reported cases of HSV-associated GBS. Herpetic brainstem
      encephalitis cases of poor prognosis are known, but only 2 cases of benign
      brainstem encephalitis secondary to HSV infection, in which there was acute
      ophthalmoplegia and clinical features consistent with those of BBE have been
      reported.

PMID- 11442446
TI  - Phenytoin cerebellopathy without epilepsy.

PMID- 11442447
TI  - 5-Hydroxytryptamine-induced microvascular pressure transients in lungs of
      anaesthetized rabbits.
AB  - We determined lung microvascular pressure transients induced by 5
      hydroxytryptamine (5HT), by the micropuncture technique. We mechanically
      ventilated anaesthetized (halothane 0.8%), open-chested rabbits, in which we
      recorded pulmonary artery (PA), left atrial (LA) and carotid artery pressures and
      cardiac output. For 4-min periods of stopped ventilation, we constantly inflated
      the lung with airway pressure of 7 cmH2O, then micropunctured the lung to
      determine pressures in arterioles and venules of 20-25 microm diameter. An
      intravenous bolus infusion of 5HT (100 microg), increased total pulmonary
      vascular resistance by 59%. Prior to 5HT infusion, the arterial, microvascular
      and venous segments comprised 30, 50 and 19% of the total pulmonary vascular
      pressure drop, respectively. However 14 s after 5HT infusion, the PA-arteriole
      pressure difference (arterial pressure drop) increased 46%, while the venule-LA
      pressure difference (venous pressure drop) increased >100%. The arteriole-venule
      pressure difference (microvascular pressure drop) was abolished. The increase in
      the arterial pressure drop was maintained for 4.8 min, whereas the increased
      venous pressure drop reverted to baseline in <1 min. We conclude that in the
      rabbit lung in situ, a 5HT bolus causes sustained arterial constriction and a
      strong but transient venous constriction.

PMID- 11442448
TI  - Intermittent hypoxia improves atrial tolerance to subsequent anoxia and reduces
      stress protein expression.
AB  - We tested the hypothesis that 21 days of intermittent hypoxia (IH) increases the
      tolerance of the spontaneously beating guinea-pig double atria preparation to
      acute in-vitro hypoxia, and reduces cardiac stress protein expression. A total of
      28 guinea-pigs were divided into four groups: (i) IH; (ii) IH + in-vitro hypoxia
      (IH + IV); (iii) control (CON); (iv) control + in-vitro hypoxia (CON + IV). The
      IH animals were exposed to 8% O2/0.3% CO2 for 12 h day-1 for 21 days. Normoxic
      controls were exposed to room air for the same duration. Acute in-vitro hypoxia
      (20, 10, 5 and 0% O2 in 5% CO2) was introduced into the atrial preparation. Heat
      shock protein (Hsp) 70 and Hsp90 content were determined by Western blotting.
      Intermittent hypoxia groups demonstrated typical responses to chronic hypoxic
      exposure, characterized by significantly (P < 0.05) lower body weights, reduced
      growth rates and increased heart weight/body weight ratios. In the CON + IV
      group, in-vitro hypoxia reduced heart rate (20% O2, -30 +/- 8 beats min (-1); 10%
      O2, -34 +/- 8 beats min (-1); 5% O2, -37 +/- 9 beats min (-1) and 0% O2, -51 +/-
      9* beats min (-1): *P < 0.05 vs. 20% O2). At 0% O2, the decrease in the rate
      response was significantly attenuated in the IH + IV (-30 +/- 8 beats min (-1);
      n=10) compared with the CON + IV (-51 +/- 9 beats min (-1); n=10). IH
      significantly reduced atrial Hsp70 and Hsp90 expression, however, levels of both
      proteins were unchanged in the ventricle. Furthermore, Hsp90 and to a lesser
      degree Hsp70 in the atria remained suppressed following in-vitro hypoxia in the
      IH group. Our results show that the increased resistance of the isolated atria to
      anoxia following IH may contribute to the concomitant reductions in basal and
      hypoxia-induced Hsp expression as the overall stress response is reduced.

PMID- 11442449
TI  - Acute effects of pulmonary artery banding in sheep on right ventricle pressure
      volume relations: relevance to the arterial switch operation.
AB  - The first stage of the two-stage arterial switch operation (ASO) for
      transposition of the great arteries (TGA) is associated with depressed
      ventricular function and an unstable immediate post-operative course. It is
      unclear if this is because of the acute increase in afterload of the thin-walled,
      low-pressure ventricle by pulmonary artery banding (PAB). To determine the acute
      effects of afterload increase on the contractile function of thin-walled
      ventricles, we studied the right ventricular pressure-volume relations of seven
      sheep before and 30 min after PAB using combined pressure-conductance catheters
      during inflow reduction. Load independent indices of systolic and diastolic
      performance were derived from these relations. Pulmonary artery banding increased
      the mean ratio between right and left ventricular systolic pressure from 0.34 +/-
      0.05 to 0.64 +/- 0.10, P < 0.05 (mean +/- SD). There were no significant changes
      in heart rate and end-systolic volume after banding although there was an
      incremental trend in the end-diastolic volume and stroke volume. Right
      ventricular output (530 +/- 163-713 +/- 295 mL min (-1), P < 0.05), slope of the
      end-systolic pressure-volume relation (ESPVR) (3.7 +/- 2.8-10.0 +/- 4.8 mmHg mL (
      1), P < 0.05) and slope of the pre-load recruitable stroke work (PRSW) relation
      (9.6 +/- 1.8-15.0 +/- 3.1 mmHg, P < 0.05) were significantly increased indicating
      improved contractile state after banding. The diastolic function curve was
      unchanged after banding although the right ventricle (RV) was operating at a
      larger end-diastolic volume. Hence, the RV of sheep responded to acute pressure
      overload by demonstrating enhanced contractility and evidence of the Frank
      Starling mechanism without associated change in right ventricular diastolic
      performance.

PMID- 11442450
TI  - An ordinary mixed meal transiently impairs endothelium-dependent vasodilation in
      healthy subjects.
AB  - This study was designed to evaluate the effects of an ordinary mixed meal on
      endothelium-dependent vasodilation. Ten young healthy volunteers were given a
      mixed meal (minced meat sauce with rice, 900 kcal, 34% of the energy content was
      fat). In the fasting state, at 60 and 120 min after the start of the meal,
      endothelium-dependent vasodilation and endothelium-independent vasodilation were
      evaluated by local infusion of metacholine (4 microg min (-1)) and sodium
      nitroprusside (10 microg min (-1)) in the brachial artery. Blood flow in the
      forearm was measured using venous occlusion plethysmography. Endothelium
      dependent vasodilation decreased from 15.4 +/- 3.3 (mean +/- SD) at fasting to
      13.7 +/- 3.5 mL min (-1) (100 mL tissue)-1 (P < 0.01) 60 min after feeding, but
      had returned to the fasting level at 120 min. At 60 min, but not in the fasting
      state, the serum level of free fatty acids was inversely related to endothelium
      dependent vasodilation (r=-0.74, P < 0.05), although no significant net changes
      in FFA levels were seen. Endothelium-independent vasodilation was not affected by
      the mixed meal. No similar attenuations in endothelium-dependent vasodilation
      were seen during control meals. In conclusion, an ordinary mixed meal transiently
      attenuated endothelium-dependent vasodilation. Free fatty acids may be involved
      in this effect on endothelial function.

PMID- 11442451
TI  - Enhanced intestinal motility influences absorption in anaesthetized rat.
AB  - The subject of this investigation was to study influence of the intestinal
      motility on absorption of 3-o-methyl-D-glucose (3-OMG), mannitol and polyethylene
      glycol (PEG 4000), used as absorption route markers, while monitoring
      cardiovascular parameters in an intestinal in situ model in rats. Rats were
      anaesthetized with Inactin(R) and Rapinovet(R). A segment of duodenum,
      approximately 10 cm, was perfused single-pass with saline containing unlabelled
      and radioactive 3-OMG, PEG 4000 or mannitol. The PEG 4000 was recovered almost
      completely in the intestinal perfusate suggesting an intact mucosal integrity.
      Most animals exhibited an intestinal contractile activity resembling fed motility
      except seven out of 19 given Rapinovet, which showed a 'burst-type' pattern
      resembling migrating motor complex (MMC). Absorption of 3-OMG in rats with MMC
      like motility appears to be lower than in rats with fed-like motility, while no
      such difference was seen for mannitol. Moreover, there was a positive correlation
      (r 2=0.75) between intestinal activity (fed) and absorption of 3-OMG, but not
      with absorption of mannitol. The carrier-mediated absorption of 3-OMG was not
      only influenced by intestinal motility, but also by its pattern. This was not
      observed with mannitol, which is passively absorbed.

PMID- 11442452
TI  - Expression of heat shock protein 72 in atrophied rat skeletal muscles.
AB  - Changes in the expression of heat shock protein 72 (HSP72) in response to
      atrophic-inducing perturbations of muscle involving chronic mechanical unloading
      and denervation were determined. Adult male Wistar rats were assigned randomly to
      a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU
      plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN
      group. Tenotomy and DEN involved cutting the Achilles tendon and removing a
      segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the
      soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P <
      0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat
      shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN
      + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05).
      Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU
      + TEN group. Hind limb unloading alone had little effect on the HSP72 level in
      either muscle. Reduced levels of HSP72 were associated with a decreased soleus
      (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results
      indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are
      responsive to a chronic decrease in the levels of loading and/or activation and
      suggest that the neuromuscular activity level and the presence of innervation of
      a muscle are important factors that induce HSP72 expression.

PMID- 11442453
TI  - Regulation of synthesis of fibrillar collagens in rat skeletal muscle during
      immobilization in shortened and lengthened positions.
AB  - Immobilization has been shown to cause muscle atrophy and decreased total
      collagen synthesis in skeletal muscle. These changes can be counteracted by
      stretch. The purpose of this study was to find out the early effects of
      immobilization in shortened and lengthened positions on expression of type I and
      III collagen at pre- and post-translational level. The mRNA levels of type I and
      III collagen, prolyl 4-hydroxylase activity, total collagen concentration and the
      proportions of type I and III collagens were analysed in soleus (SOL),
      gastrocnemius (GM), extensor digitorum longus and tibialis anterior (TA) muscles
      during immobilization in shortened and lengthened positions for 1, 3 and 7 days.
      The mRNA levels for type I and III collagens decreased during 3-7 days in all
      muscles, except TA. In shortened GM and SOL, the mRNA level of type I collagen
      was lower than in the corresponding lengthened muscles. Prolyl 4-hydroxylase
      activity decreased in all muscles during 3-7 days. The activity in shortened GM
      was 30-37% lower than in the lengthened one during 3-7 days. Total collagen
      concentration and proportions of type I and III collagen showed no change during
      the 7-day immobilization period. The present study suggests that immobilization
      results in rapid down-regulation of total muscular collagen synthesis and that
      the timing and degree is roughly similar in type I and III collagens. Stretch
      seems to partially counteract these effects. Immobilization effect and the
      partially preventive effect of stretch on down-regulation of gene expression of
      prolyl 4-hydroxylase and fibrillar collagens during immobilization seems to be
      greater in weight-bearing SOL and GM than ankle joint dorsiflexors.

PMID- 11442454
TI  - Effect of 10-day cast immobilization on sarcoplasmic reticulum calcium regulation
      in humans.
AB  - This study investigated the effects of 10-day lower limb cast immobilization on
      sarcoplasmic reticulum (SR) Ca2+ regulation. Muscle biopsies were analysed in
      eight healthy females for maximal rates of SR Ca2+ release, Ca2+ uptake and Ca2+
      ATPase activity at control, during immobilization at day 3 (IM 3), day 6 (IM 6)
      and day 10 (IM 10). Quadriceps muscle cross-sectional area (CSA) and 1-repetition
      maximum (1RM) leg extension strength were measured to determine the extent of
      muscle size and strength adaptations. Muscle CSA and strength decreased following
      10 days of immobilization (11.8 and 41.6%, respectively, P < 0.01). A decrease in
      SR Ca2+ uptake rate (analysed per g wet wt) was found at IM 3 (13.2%, P=0.05),
      with a further decrease at IM 10 (19.8% from control, P < 0.01). At IM 10, a
      decrease in SR Ca2+ uptake rate (per mg protein) also occurred (19.9%, P < 0.01).
      Sarcoplasmic reticulum Ca2+ ATPase activity and rate of Ca2+ release were not
      altered with 10 days of immobilization. This study observed a decrease in SR Ca2+
      uptake rate, muscular atrophy and strength loss over 10 days of immobilization in
      humans.

PMID- 11442455
TI  - Influence of ruminal water-loading on renal sodium excretion and water intake
      following feeding in sheep.
AB  - We investigated the effect of ruminal water loading before feeding on the
      natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of
      chaff drank 1360 +/- 150 mL during the 5 h immediately following feeding and
      increased renal Na excretion. Plasma Na concentration increased by 4 mmol L (-1)
      and plasma osmolality by 9 mosmol kg (-1) within 1.5 h and remained elevated. A
      rumen load of water administered before feeding prevented the increases in plasma
      Na and osmolality without affecting feeding. The natriuresis, water drinking and
      vasopressin secretion in response to feeding were abolished. Total sodium
      excreted during the experiment was halved in water-loaded animals compared with
      untreated animals (30.4 +/- 2.1 mmol (-1) cf. 63.8 +/- 2.9 mmol-1; P < 0.01).
      Ruminal loading with isotonic saline caused a 33% reduction in postprandial
      drinking, however, reducing cerebrospinal fluid NaCl concentration abolished
      postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran
      appeared to delay the onset of water intake without changing the total volume of
      water drunk, suggesting a role of plasma volume in initiating drinking. We
      conclude from the data that central osmoregulatory mechanisms that include
      increased sodium excretion as well as thirst and vasopressin release are
      activated following food intake by sheep.

PMID- 11442456
TI  - Prostatic MR imaging in the dark.

PMID- 11442457
TI  - Prostatic MR imaging. Accuracy in differentiating cancer from other prostatic
      disorders.
AB  - PURPOSE: We assessed the accuracy of MR imaging in differentiating between cancer
      and other prostatic disorders, and evaluated the diagnostic criteria for various
      prostatic diseases. MATERIAL AND METHODS: A total of 74 endorectal coil MR
      studies were performed on 72 patients. Twenty patients had prostatic cancer, 20
      benign prostatic hyperplasia (BPH), 4 acute bacterial prostatitis, 5 chronic
      bacterial prostatitis (2 also belonging to the previous category), 19 chronic non
      bacterial prostatitis/chronic pelvic pain syndrome, and 6 were symptomless
      voluntary controls. All studies were interpreted by two experienced radiologists
      in random order. Radiologists were blinded to all clinical data including the age
      of the patients. Based on MR findings, both radiologists filled in a form
      covering diagnostic criteria and diagnosis. RESULTS: Accuracy in diagnosing
      prostate cancer was 74%. Sensitivity was 50% and specificity 83%, and positive
      and negative predictive values were 53 and 82%, respectively. Bacterial
      prostatitis showed some features similar to carcinoma. Abundant BPH rendered
      cancer detection more difficult. No diagnostic criterion was clearly better than
      the others. Interobserver agreement on the MR diagnosis ranged from moderate to
      good. CONCLUSION: Without knowledge of accurate clinical data, MR seems to be too
      insensitive in detecting prostate cancer to be used as a primary diagnostic tool.

PMID- 11442458
TI  - Long-term follow-up of reflux nephropathy in adults with vesicoureteral reflux-
      radiological and pathoanatomical analysis.
AB  - PURPOSE: To study the long-term development of urographic renal morphology in
      adults with vesicoureteral reflux, to investigate the relationship between renal
      damage and reflux grade, and to analyse the association between the long-term
      urographic outcome and the occurrence of acute pyelonephritis and reflux during
      follow-up. The purpose was also to try to distinguish between acquired and
      developmental renal damage, based on analyses of renal histological specimens and
      urographic features, and to analyse associated congenital urogenital
      abnormalities and family history of reflux, reflux nephropathy, urological
      malformation or death from end-stage renal disease. MATERIAL AND METHODS: Renal
      damage was identified in 100 (83 women) of 115 adults, selected because of
      documented reflux. Eighty-seven patients had two urographies done (median
      interval 14.3 years). The extent and progression of renal damage were assessed
      and features of developmental renal damage were determined. Histological renal
      specimens were available in 23 patients with renal damage. RESULTS AND
      CONCLUSIONS: The extent of renal damage correlated positively with the severity
      of reflux. No renal damage developed during the follow-up in 45 previously
      undamaged kidneys and progression of renal damage was rare (4 of 120 previously
      damaged kidneys), despite persisting reflux in half of the cases and episodes of
      acute pyelonephritis during follow-up. Thus, repeated renal imaging is rarely
      justified in adults with reflux nephropathy. Histological examination showed
      "chronic pyelonephritis" in all 23 cases and co-existing renal dysplasia in 1
      case. The detailed urographic analysis did not reveal support for developmental
      renal damage. High frequencies of associated congenital urogenital abnormalities
      and of a positive family history were found. Thus, congenital and/or hereditary
      factors cannot be discarded as background factors for the development of renal
      damage.

PMID- 11442459
TI  - Diffusion-weighted MR and apparent diffusion coefficient in the evaluation of
      severe brain injury.
AB  - PURPOSE: To study apparent diffusion coefficient (ADC) maps in severely brain
      injured patients. MATERIAL AND METHODS: Four deeply comatose patients with severe
      brain injury were investigated with single-shot, diffusion-weighted, spin-echo
      echoplanar imaging. The tetrahedral diffusion gradient configuration and four
      iterations of a set of b-values (one time of 0 mm2/s, and four times of 1000
      mm2/s) were used to create isotropic ADC maps with high signal-to-noise ratio.
      ADC values of gray and white matter were compared among patients and 4 reference
      subjects. RESULTS: One patient was diagnosed as clinically brain dead after the
      MR examination. The patient's ADC values of gray and white matter were
      significantly lower than those of 3 other brain-injured patients. In addition the
      ADC value of white matter was significantly lower than that of gray matter.
      CONCLUSION: The patient with fatal outcome shortly after MR examination differed
      significantly from other patients with severe brain injury but non-fatal outcome,
      with regard to ADC values in gray and white matter. This might indicate a
      prognostic value of ADC maps in the evaluation of traumatic brain injury.

PMID- 11442460
TI  - Neonatal periventricular-intraventricular hemorrhage. Subacute and chronic MR
      findings.
AB  - PURPOSE: To evaluate MR findings at subacute and chronic stages after neonatal
      periventricular-intraventricular hemorrhage (PIVH), and to determine the clinical
      significance of follow-up MR. MATERIAL AND METHODS: Twenty-six children
      (estimated gestational age, 23-39 weeks; mean 29 weeks) with a history of
      previous PIVH underwent MR examination during their subacute and chronic clinical
      courses. PIVHs were initially detected with ultrasound examination in all cases.
      PIVH was divided into three grades (mild, moderate, and severe) according to the
      findings at the initial US studies, which were correlated to the MR findings.
      RESULTS: Abnormal signal intensities related to hemorrhage were demonstrated in
      10 of 21 patients (47.6%) on initial MR studies; the very low signal intensities
      on T2-weighted images found on the periventricular wall with a linear or a spotty
      shape had disappeared at one year after the initial US. The children with
      ventriculomegaly and periventricular leukomalacia (PVL) were increased in number
      on the follow-up studies. CONCLUSION: MR imaging provided valuable information
      about the consequences of neonatal PIVH such as developments of ventriculomegaly
      or PVL. It is noteworthy that hemorrhagic lesions could not be detected in half
      of the cases at the subacute or chronic stage of PIVH.

PMID- 11442461
TI  - MR imaging of the lingual thyroid. Comparison to other submucosal lesions.
AB  - PURPOSE: To study MR findings for clues to the diagnosis of lingual thyroid.
      MATERIAL AND METHODS: MR findings and clinical and scintigraphic data of 5 cases
      of lingual thyroid were reviewed and the MR findings were compared to those of 16
      cases of other submucosal lesions in the base of the tongue. RESULTS: Four of the
      5 patients with lingual thyroid were women and all had hypothyroidism. MR imaging
      depicted lingual thyroid in the midline in the base of the tongue (n=5) and
      additional ectopic thyroid glands in the floor of the mouth (n=2) or between the
      right and left sternohyoid muscles (n=1). Ectopic thyroid glands appeared
      isointense or hyperintense relative to muscle tissue on T1-weighted images and
      showed slight or fair contrast enhancement. All glands had low to intermediate T2
      signal, which was also seen in 1 case of non-Hodgkin's lymphoma and 1 case of
      adenoid cystic carcinoma. All ectopic thyroid glands had well-defined margins,
      whereas malignant tumors tended to have ill-defined margins and to invade the
      surrounding structures. All but the 5 cases of lingual thyroid had an MR
      demonstrable thyroid gland in the normal cervical position. CONCLUSION: A well
      defined mass of low-intermediate T2 signal in the midline base of the tongue,
      neither with invasive tendency nor with a cervical thyroid gland in the normal
      site on MR imaging, may strongly indicate lingual thyroid.

PMID- 11442462
TI  - Dynamic helical CT-guided needle localization of non-palpable and
      mammographically occult breast lesions. Case reports.
AB  - Dynamic helical CT-guided needle localization of non-palpable and
      mammographically occult breast lesions is described. Dynamic helical CT-technique
      enabled fast volume scanning of the whole breast during the early contrast
      enhancement phase, which provided sufficient contrast to localize the target
      lesions. The procedures were successfully completed without complications.

PMID- 11442463
TI  - Detection of myocardial ischemia by electron beam CT. Experimental studies.
AB  - PURPOSE: To determine if contrast-enhanced electron beam CT (EBCT) can detect
      areas of acute myocardial ischemia, and if pharmacological stress testing
      improves the diagnostic accuracy of EBCT. MATERIAL AND METHODS: We injected 0.5
      ml/kg and 1.0 ml/kg b.w. of iopromide at a rate of 4 ml/s into the right atrium
      of 5 ventilated female minipigs at rest and after occlusion of the left anterior
      descending (LAD) coronary artery. Both ventricles were examined at six short axis
      levels with an EBCT unit. Myocardial perfusion was calculated from the time
      density curves of four left ventricular myocardial segments and the aorta. We
      also tested the effect of the contrast agent on myocardial density after i.v.
      administration of 0.6 mg/kg dipyridamole before and after LAD occlusion. RESULTS:
      At rest, the contrast agent increased myocardial density by 28+/-2 HU,
      corresponding to a myocardial perfusion estimate of 67+/-7 ml/min/100 g. After
      dipyridamole, myocardial density increased by 29+/-4 HU. Following occlusion of
      the LAD, anteroseptal myocardium displayed 10+/-4 HU density increase. The area
      of non-enhancement corresponded to ischemic myocardium in stained pathologic
      sections. CONCLUSION: Contrast-enhanced stress EBCT can be used to detect areas
      of myocardial ischemia, and EBCT stress perfusion imaging may be necessary to
      consistently differentiate ischemic from non-ischemic myocardial tissue.

PMID- 11442464
TI  - Long-term results of combined surgical and radiological intervention in
      complicated aortic dissection type-A. A case report.
AB  - We report the long-term results of combined surgical and radiological
      intervention in a patient with complicated aortic dissection, type-A. Following
      surgical graft-repair of a dissected part of the ascending aorta, embolization of
      the splenic artery, and stenting of the major abdominal arteries and of the left
      renal artery, was performed. The patient was able to return to normal active
      life, and all stented arteries remained patent after 32 months. A stent that was
      mispositioned across the aortic lumen did not cause any symptoms.

PMID- 11442465
TI  - Nontumorous perfusion abnormalities of liver parenchyma adjacent to the falciform
      ligament as revealed by angiographic helical CT and angiography.
AB  - PURPOSE: To investigate nontumorous abnormalities in the liver around the
      falciform ligament as revealed by arteriography and helical CT arterial
      portography (CTAP) and helical CT during hepatic arteriography (CTHA). MATERIAL
      AND METHODS: One hundred and seventeen patients simultaneously underwent hepatic
      arteriography and CTAP and CTHA of the common hepatic artery. The number, size,
      and shape of nontumorous defects of portal perfusion in the liver adjacent to the
      falciform ligament on CTAP as well as the nontumorous contrast enhancement in the
      same area on CTHA were determined. In 1 case, in which nontumorous enhancement
      was observed on CTHA, selective arteriography from the gastric arteries was
      performed. RESULTS: On CTAP a nontumorous area of decreased portal perfusion of
      the liver around the falciform ligament was detected in 18 (15.4%) of the 117
      patients, while nontumorous enhancement on CTHA was seen in 7 (6.0%). In 4
      patients, both of these nontumorous abnormalities were observed. In the patient
      undergoing selective gastric arteriography, nonportal venous inflow to the liver
      in the direction to the liver adjacent to the falciform ligament was seen.
      CONCLUSION: One cause of nontumorous vascular abnormalities adjacent to the
      falciform ligament as shown on angiographic helical CT is aberrant gastric venous
      inflow to this region.

PMID- 11442466
TI  - Imaging and estimation of the prognostic features of primary sclerosing
      cholangitis by ultrasonography and MR cholangiography.
AB  - PURPOSE: To evaluate the ability of US and MR cholangiography (MRC) to detect
      bile duct changes and prognostic signs of primary sclerosing cholangitis (PSC)
      seen at endoscopic retrograde cholangiography (ERC). MATERIAL AND METHODS: In a
      prospective study, 9 patients with PSC underwent US, MRC, MR imaging and ERC of
      the bile ducts and the liver. Eight age- and sex-matched control patients were
      examined with MRC, MR imaging and ERC. A segmental comparison was performed to
      assess the ability of MRC-MR and US to reveal the accurate ductal involvement in
      different segments of the biliary tree and the specific criteria of poor
      prognostic outcome in PSC. The ability of MRC-MR to detect the presence of PSC in
      different patients was analysed blindly. RESULTS: MRC-MR depicted changes of PSC
      correctly in 9 patients (radiologist 1) and in 8 patients with 1 false-positive
      finding (radiologist 2) in the blinded analysis. In the segmental comparison, MRC
      missed especially bile duct dilatations. MRC was too pessimistic in the
      evaluation of the outcome. US detected features suggestive of PSC in 8 patients
      (radiologist 3). US was unable to show the predictors of poor outcome.
      CONCLUSION: MRC and US seem to be useful in the detection of PSC. US is unable
      and MRC is too pessimistic to estimate the outcome of PSC.

PMID- 11442467
TI  - MR imaging of primary, secondary, and mixed forms of lymphedema.
AB  - PURPOSE: To describe the pathological features and assess the diagnostic
      information of different MR sequences in patients with primary, secondary, and
      mixed (phlebo-, lipophlebo-, or lipolymphedema) forms of lymphedema of the lower
      leg. MATERIAL AND METHODS: In 26 patients with clinical diagnoses of primary
      (n=10), pure secondary (n=4), mixed (n=9) and combined secondary and mixed forms
      of lymphedema (n=3), MR imaging was performed with coronal and axial T1 SE, T2
      TSE, fat-suppressed (SPIR) T2 sequences and axial T1 SE after i.v. injection of
      Gd-DTPA. RESULTS: In 24 patients there was a honeycomb pattern in the subcutis
      with a signal intensity corresponding to fluid (n=11), fibrosis (n=3), or both
      (n=10). Five patients with primary lymphedema showed subfascial fluid
      accumulation. Dermal edema was noted in 23 patients. Fat or edema components in
      the muscles were mostly seen in patients with phlebolymphedema. The honeycomb
      pattern was best seen on coronal T1 images, and fluid accumulations on axial SPIR
      T2 images. Fibrosis was only assessible from the T2 TSE sequence. Gd-DTPA did not
      improve the diagnostic information. CONCLUSION: For evaluation of lymphedema and
      its mixed forms, an axial T2-weighted SPIR sequence in conjunction with a coronal
      T1 SE sequence are sufficient.

PMID- 11442468
TI  - MR imaging of displaced meniscal tears of the knee. Importance of a
      "disproportional posterior horn sign".
AB  - PURPOSE: Meniscal tears associated with displaced fragments are clinically
      significant. We propose the "disproportional posterior horn sign" as a supportive
      criterion to identify a posterocentrally displaced meniscal fragment on MR
      imaging studies. If the meniscal posterior horn in the central portion appears
      larger than that in the peripheral section, it is considered positive for
      "disproportional posterior horn sign". MATERIAL AND METHODS: MR images obtained
      in 42 patients with 43 lesions, confirmed to have displaced meniscal tears, were
      included in this study. The MR images were retrospectively evaluated for the
      presence of the "disproportional posterior horn sign", as well as the other known
      signs. RESULTS: The "disproportional posterior horn sign" was seen in 9 (20.9%)
      of 43 lesions, including 1 lateral discoid meniscal tear, 5 lateral meniscal
      tears and 3 medial meniscal tears. Five of them also had other signs of a
      displaced meniscal fragment. However, the remaining 4 cases only exhibited the
      "disproportional posterior horn sign". For the other MR signs, the "absent bow
      tie sign" was detected in 40 (93%) of 43 lesions, the "flipped meniscus sign" in
      27 (62.8%) of 43 lesions, the "double posterior cruciate ligament sign" in 17
      (39.5%) of 43 lesions and the "notch fragment sign" in 22 (51.2%) of 43 lesions.
      CONCLUSION: The "disproportional posterior horn sign" is helpful in demonstrating
      a posterocentrally displaced meniscal fragment, especially when other
      characteristic signs are unremarkable or absent.

PMID- 11442469
TI  - Ionic and non-ionic contrast agent-mediated endothelial injury. Quantitative
      analysis of cell proliferation during endothelial repair.
AB  - PURPOSE: To quantitatively evaluate endothelial injury in vivo and to assess the
      time course of cellular repair after endothelial cell exposure to ionic and non
      ionic contrast media. MATERIAL AND METHODS: Local changes at the cellular level
      following intraaortic injection of 1 ml of the ionic contrast agent ioxithalamate
      or 1 ml of the non-ionic contrast agent iomeprol, each with an iodine content of
      300 mg/ml, were investigated using rat endothelium as an in vivo model. A
      sorbitol solution iso-osmolar to iomeprol served as control. Quantitative
      analysis of endothelial changes by autoradiography of 3H-thymidine-labeled
      endothelial cells was assessed after 3, 5 and 10 days, determining the 3H
      thymidine index and the DNA synthesis rate. RESULTS: Ioxithalamate showed a clear
      harmful effect on the endothelium, with an elevated 3H-thymidine index of 7.68%
      on day 3 and 6.89% on day 5, versus 2.97% on day 3 and 2.55% on day 5 for
      iomeprol and 2.29% on day 3 and 1.91% on day 5 for the control. CONCLUSION: Ionic
      contrast agents lead to reversible transient focal endothelial cell injury. No
      such side effect was detectable for non-ionic contrast agents.

PMID- 11442470
TI  - Radiological image data migration. Practical experience and comparison of the
      costs of work.
AB  - PURPOSE: To identify costs deriving from data migration of obsolete digital
      archives by measuring the workload, and to analyse migration-associated problems.
      MATERIAL AND METHODS: Two digital archives were used (DTL and MOD) and the
      capacity of these archives could no longer support the needs of the Medical
      Imaging Centre. The entire content of the DLT archive and selected data from the
      MOD archive were transferred to the current higher capacity (17 TB) tape archive.
      The running time of work processes was measured by self-reporting, and the cost
      of work was calculated. RESULTS: The transfer of 43,096 studies required 314
      working hours over the course of 15 months in total. The work was partly manual,
      partly automatic. The percentage of non-retrievable MOD images was 35. Less than
      0.2% of the DLT image transfers failed due to incorrect patient or image data.
      The MOD - DLT transfer cost was six times higher per study than the DLT - DLT
      transmission cost. CONCLUSION: At present, data migration may be inevitable as
      the amount of data increases and technology advances. The data transfer proved to
      be labour intensive, with high fault sensitivity regarding the MOD archive. The
      cost of work of data migration was 0.4% of estimated digital archiving total
      yearly cost. Automated data migration is preferable.

PMID- 11442471
TI  - Erythrophagocytosis associated with AML-M5 and t(8;16).

PMID- 11442472
TI  - Acute cerebellar syndrome following intermediate-dose cytarabine.

PMID- 11442473
TI  - Near-patient testing devices to monitor oral anticoagulant therapy.

PMID- 11442474
TI  - Origins of the discipline 'neonatal haematology', 1925-75.

PMID- 11442475
TI  - Protein assays for diagnosis of Wiskott-Aldrich syndrome and X-linked
      thrombocytopenia.
AB  - Mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASp) give
      rise to Wiskott-Aldrich syndrome (WAS), a condition that exhibits a wide spectrum
      of clinical severity. Patients may develop mild thrombocytopenia or suffer from a
      wide range of associated disorders including eczema, immune dysfunction,
      autoimmune disease and malignancy. The clinical diagnosis of Wiskott-Aldrich
      syndrome (WAS) can be difficult and is usually supported by the detection of WASp
      gene mutations using genetic analysis. Recently, protein-based assays have been
      used to demonstrate the absence of WASp in patients known to have WASp gene
      mutations. We have now reversed this approach and report on the use of immunoblot
      assays to rapidly diagnose WAS in 13 patients. There was a complete absence of
      WASp in 10 out of 13 patients and an abnormal protein form was detected in the
      remaining three patients. In all cases, subsequent genetic analysis confirmed the
      presence of a WASp gene mutation. We believe that protein-based assays should be
      employed as the first line of investigation in the diagnosis of WAS spectrum
      disorders.

PMID- 11442476
TI  - Congenital thrombocytopenia and radio-ulnar synostosis: a new familial syndrome.
AB  - The association of bone marrow failure and skeletal defects has been frequently
      noted, however, the genetic basis for most of these syndromes remains unclear. We
      describe a previously uncharacterized autosomal dominant syndrome of
      amegakaryocytic thrombocytopenia associated with radial-ulnar synostosis. The
      clinical features of this syndrome appear to be distinct from other similar
      conditions, including Fanconi's anaemia and thrombocytopenia-absent radii (TAR).
      The physical findings at diagnosis and clinical management of each case are
      detailed, as well as a discussion of this disorder in the context of other
      syndromes in which marrow failure and skeletal defects are prominent features. We
      also review recent developments in molecular genetics that may provide important
      clues to the underlying aetiology of this condition.

PMID- 11442477
TI  - The storage defects in grey platelet syndrome and alphadelta-storage pool
      deficiency affect alpha-granule factor V and multimerin storage without altering
      their proteolytic processing.
AB  - Among proteins stored in alpha-granules, multimerin and factor V share unusual
      features: they bind to each other, are proteolysed to unique forms and are stored
      eccentrically in alpha-granules. These unique features of their processing led us
      to study these proteins in alpha delta storage pool deficiency (alphadelta-SPD)
      and grey platelet syndrome (GPS, alpha-SPD), two conditions known to impair alpha
      granule protein storage. Platelet factor V and multimerin were severely reduced
      in GPS, whereas they ranged from reduced to normal in alphadelta-SPD. The
      platelet levels of factor V and multimerin in these disorders indicated
      multimerin deficiency was not predictive of platelet factor V deficiency,
      although it reduced the amount of multimerin associated with platelet factor V.
      In GPS only, the defect in storing proteins was associated with increased
      multimerin and multimerin-factor V complexes in plasma. Like normal platelets,
      GPS and alphadelta-SPD platelets contained factor V mainly in granules. Platelet
      factor V and multimerin were proteolysed to normal platelet forms in GPS and
      alphadelta-SPD platelets, indicating that these conditions preserve some aspects
      of normal alpha-granule protein processing. Although we found factor V can be
      stored in platelets deficient in multimerin, our data indicate that multimerin
      storage influences the point at which multimerin binds factor V.

PMID- 11442478
TI  - Characterization of a partial prostaglandin endoperoxide H synthase-1 deficiency
      in a patient with a bleeding disorder.
AB  - Thromboxane A2 (TXA2), synthesized in platelets, is a powerful aggregating agent
      and vasoconstrictor. To induce platelet aggregation, the platelets' enzyme,
      prostaglandin endoperoxide H synthase-1 (PGHS-1), first converts arachidonic acid
      (AA) into prostaglandin H2 (PGH2). PGH2 is then converted by the enzyme
      thromboxane synthase into TXA2. Finally, TXA2 is secreted and can activate the
      TXA2 receptor on the platelet surface. The importance of TXA2 in haemostasis has
      been demonstrated by the presence of a bleeding tendency in patients showing an
      inherited defect in the TXA2 production pathway. We studied an 18-year-old woman
      with a lifelong bleeding disorder, moderate thrombocytopenia (55-71 x 109/l) and
      a prolonged bleeding time (12.5 min). Her platelets aggregated in the presence of
      both PGH2 and a stable TXA2 analogue, but did not aggregate in the presence of
      AA. The activity of PGHS-1 in platelets, measured using thin-layer chromatography
      and radioactive counting of TXA2 formation from [14C]-AA, was reduced to 13% of
      the activity measured in control subjects. PGHS-1 protein levels, measured using
      Western blot analysis, were also markedly reduced to 10% of control values. Such
      levels of PGHS-1 enzyme were too low to sustain platelet aggregation in the
      patient, even if the enzyme was active. The PGHS-1 protein level was also reduced
      in the patient's immortalized B lymphocytes, suggesting a systemic expression
      defect. Northern blot analysis was then carried out with poly (A)+ RNA extracted
      from the patient's immortalized B lymphocytes. PGHS-1 mRNA was detected as a 2.8
      kb band in both the patient and control. The intensity of the band representing
      the patient's PGHS-1 mRNA was similar to that of the control subject. The
      Northern blot result suggests a normal transcriptional rate of the PGHS-1 gene
      for the patient. Therefore, the defect responsible for the reduced levels of PGHS
      1 protein is probably post-transcriptional.

PMID- 11442479
TI  - Determination of heparin-platelet factor 4-IgG antibodies improves diagnosis of
      heparin-induced thrombocytopenia.
AB  - Only a few patients with heparin-induced antibodies develop heparin-induced
      thrombocytopenia (HIT). In this study, we investigated whether different
      immunglobulin classes can be used to differentiate between antibody-positive
      patients with and without HIT. Four different patient populations were
      investigated: 32 patients with the immune type of HIT with thromboembolic
      complications, 13 patients with HIT without thromboembolism, 24 patients with
      heparin-platelet factor 4 (PF4) antibodies without clinical symptoms of HIT, and
      20 heparin-treated patients with thrombocytopenia caused by other reasons. In all
      patients the immunglobulin mixture of IgG, IgM and IgA, and the single
      immunglobulin classes of heparin-PF4 antibodies, were investigated. No
      significant differences between HIT patients with thromboembolic complications
      and patients with isolated HIT were found concerning the different immunglobulin
      classes. Antibody-positive patients with HIT had significantly higher levels of
      IgG antibodies than those without HIT (P < 0.05), while they did not differ
      concerning IgM and IgA antibodies. By determining IgG antibodies, the specificity
      of the enzyme-linked immunosorbent assay (ELISA) system was increased without
      loss of sensitivity. Heparin-PF4-IgG antibodies can identify patients at risk of
      developing life-threatening HIT. Future ELISAs should only include this
      immunglobulin class, as the determination of the antibody mixture may lead to
      overestimation of HIT.

PMID- 11442480
TI  - Interaction of cytokines and growth factor in the regulation of verotoxin-induced
      apoptosis in cultured human endothelial cells.
AB  - The role of CD77, inflammatory cytokines and endothelial cell growth factor
      (ECGF) in verotoxin (VT)-induced apoptosis in human umbilical vein endothelial
      cells (HUVECs) was studied. Apoptosis was detected using annexin V and propidium
      iodide staining. The expression of CD77 antigen was measured on a FACStar flow
      cytometer using specific monoclonal antibodies. Our experiments showed that
      HUVECs had very low initial levels of CD77 and were resistant to VT. Treatment
      with tumour necrosis factor alpha (TNF-alpha) resulted in a significant
      upregulation of CD77 expression and sensitized endothelial cells to VT-mediated
      apoptosis. HUVECs incubated with a combination of cytokines [TNF-alpha and
      interferon gamma (IFN-gamma), both 500 U/ml] showed more pronounced upregulation
      of CD77 expression (> sixfold at 48 h) and underwent apoptosis, suggesting that
      TNF-alpha and IFN-gamma have a synergistic effect on CD77 expression in HUVECs
      and can induce apoptosis without VT. Cells pretreated with TNF-alpha and IFN
      gamma and incubated with VT showed the most pronounced (14-fold) increase in CD77
      expression. ECGF had a partial protective effect against cytokine- and VT-induced
      apoptosis. Taken together, our data suggest that CD77 antigen is involved in the
      regulation of endothelial cell apoptosis.

PMID- 11442481
TI  - Protein S levels are lower in women receiving desogestrel-containing combined
      oral contraceptives (COCs) than in women receiving levonorgestrel-containing COCs
      at steady state and on cross-over.
AB  - This study aimed to identify specific haemostatic changes that might account for
      previous observations of higher venous thromboembolic risk among users of
      combined oral contraceptives (COCs) containing desogestrel (DSG) than
      levonorgestrel (LNG). Sixty-three current users of monophasic 30 microg oestrogen
      COCs containing either LNG or DSG omitted one pill-free interval (PFI), switching
      immediately either to the opposite formulation for one cycle or continuing with
      the same pill. Venesection followed the initial PFI after one cycle (21 tablets)
      and two cycles (42 tablets) of continuous pill taking, and after the following
      PFI. Protein S was lower in users of DSG than LNG formulations after the first
      PFI (mean +/- SD, 0.67 +/- 0.09 vs 0.76 +/- 0.10, P < 0.001) and after one cycle
      (0.61 +/- 0.09 vs 0.76 +/- 0.09, P < 0.0001). Protein S decreased when switching
      from LNG to DSG pills (0.77 +/- 0.07-0.65 +/- 0.06, P < 0.0001), mirrored by an
      increase at switching from DSG to LNG formulations (0.61 +/- 0.08-0.73 +/- 0.10,
      P < 0.005). Mean protein S levels remained within the normal range. Three
      different markers of thrombin generation remained unaltered. Potential
      explanations for COC-related thrombotic events are 'acquired resistance to
      activated protein C' or inhibition of fibrinolysis. A potential role has been
      described for protein S deficiency in both. A further triggering factor is a
      probable prerequisite for actual thrombosis, but pill-takers whose levels of
      protein S were in the lowest percentiles may be at greatest risk.

PMID- 11442482
TI  - Increased activation of protein C, but lower plasma levels of free, activated
      protein C in uraemic patients: relationship with systemic inflammation and
      haemostatic activation.
AB  - Chronic renal failure (CRF) courses with both systemic inflammatory reaction and
      haemostatic activation. We explored the relationship of these processes with
      plasma levels of free, activated protein C (APC) and complexes of APC with its
      inhibitors in patients with CRF under conservative treatment. Plasma
      concentrations of inflammatory cytokines [tumour necrosis factor alpha (TNFalpha)
      and interleukin 8], acute-phase proteins (C-reactive protein, fibrinogen, alpha1
      anti-trypsin and von Willebrand factor), and markers of haemostatic activation
      (thrombin-anti-thrombin complexes, plasmin-anti-plasmin complexes, and fibrin and
      fibrinogen degradation products) were higher in patients than in controls.
      Inflammatory and haemostatic markers were significantly and positively
      correlated. Total plasma APC and APC:alpha1-anti-trypsin (alpha1AT) complexes
      were 44% and 75% higher in patients than in controls (P = 0.0001), whereas free
      APC was 20% lower (P < 0.015). No significant difference was observed in
      APC:protein C inhibitor (PCI) complexes between both groups. The free/total APC
      ratio was significantly lower in patients than in controls (P < 0.0001). Total
      plasma APC and APC:alpha1AT were positively correlated with activation markers of
      haemostasis and acute-phase proteins, whereas free APC was inversely correlated
      with plasma levels of creatinine, acute-phase proteins and fibrin degradation
      products (FnDP). Systemic inflammation and activation of haemostasis are
      interrelated processes in CRF. APC generation was increased in response to
      elevated thrombin production, but the inflammatory reaction, associated with
      increased synthesis of alpha1AT, reduced its anticoagulant effect. Lower free
      plasma APC in CRF may be pathogenically associated with atherothrombosis, a major
      cause of death in this disease.

PMID- 11442483
TI  - Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent
      miscarriage.
AB  - While it has been established that anti-phospholipid antibodies (aPL) are
      associated with recurrent miscarriage (RM), the importance of anti-beta2
      glycoprotein 1 (GP1) IgG and anti-annexin V IgG antibodies as risk factors for RM
      is undefined. We have investigated the prevalence of anti-beta2 GP1 IgG and anti
      annexin V IgG antibodies in 54 aPL-positive and 48 aPL-negative women with RM.
      The prevalence of IgG anti-beta2 GP1 antibodies was not significantly different
      in persistently aPL-positive women with RM (7%), aPL-negative women with RM (6%)
      and the normal parous control group (3%). Anti-annexin V IgG antibody prevalence
      was significantly increased in aPL-positive women with RM compared with aPL
      negative women with RM (P = 0.01). The elevations were found in 35%, 19% and 16%
      of aPL-positive women with RM, aPL-negative women with RM and the control group
      respectively. No women showed positivity for both anti-beta2 GP1 IgG and anti
      annexin V antibodies. Anti-beta2 GP1 IgG antibodies do not appear to be
      contributory to the investigation of women with RM. Anti-annexin V antibody
      positivity, although associated with aPL positivity in women with RM, is not an
      independent risk marker.

PMID- 11442484
TI  - Epitope mapping of factor VIII inhibitor antibodies of Chinese origin.
AB  - Epitopes recognized by factor VIII (FVIII) inhibitors of Chinese origin were
      analysed by immunoblotting with full-length recombinant FVIII (rFVIII), thrombin
      activated FVIII (FVIIIa) and 16 FVIII fusion proteins synthesized by bacteria.
      Twenty-eight patients, 12 with haemophilia A and 16 with autoimmune diseases,
      were recruited. Antibodies from 22 patients showed reactivity with rFVIII, 20
      with FVIIIa, and one reacted only with FVIII fusion proteins. Of these 22 cases,
      most were reactive with A2-a2 and A3-C1-C2 of FVIII(a). Of the nine cases that
      depicted binding to the fusion proteins, three were reactive with the A domains,
      three with only the B domain, and the other three with both the A and B (or C)
      domains. An epitope for a neutralizing antibody of a haemophilia A patient,
      designated TWN-112, was localized to residues 323-390, specified by FVIII fusion
      proteins. The same epitope also appeared on an FVIII-expression phage library
      screening. Immunoabsorption of antibodies from TWN-112 with the epitope reduced
      the neutralizing activity of the inhibitor by 33%. The incidence of a1 of FVIII
      is higher, and that of a3 is lower, than previously reported. Two novel epitopes,
      reported for the first time in this paper, were localized on the 8B2 (amino acid
      residues 1022-1204) and 8A2(V) (residues 673-740) fusion proteins. These two
      epitopes were able to reduce inhibitory antibody activity by 24% and 25%
      respectively. Changes of FVIII fragment specificity were also observed in one of
      six patients for whom multiple samples, collected at different times, were
      available. Our initial finding showed that the FVIII inhibitors in these Chinese
      patients shared epitopes with those of patients from very different genetic
      backgrounds, suggesting a common mechanism for the development of FVIII
      inhibitors.

PMID- 11442485
TI  - Identification of both myeloid CD11c+ and lymphoid CD11c- dendritic cell subsets
      in cord blood.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells described to
      date. In human peripheral blood, both myeloid and lymphoid subsets of DCs have
      been identified. In contrast, cord blood (CB) DCs have recently been described as
      being exclusively of the immature CD11c- lymphoid DC subset. Using an alternative
      method of enrichment, based on a negative selection system, both lymphoid (HLA
      DR+ CD123+++ CD11c- CD33-) and myeloid (HLA-DR++ CD123+ CD11c+ CD33+) DCs were
      identified in CB. Although the majority of CB DCs showed a lymphoid phenotype, a
      significant number of CD11c+ myeloid DCs (25.6% +/- 14.5%, n = 13) were also
      present. Other markers, such as CD80 and CD83, were negative in both subsets.
      Analyses of the allostimulatory capacity of both subsets showed that freshly
      isolated CB lymphoid DCs failed to induce a potent allostimulation of naive CB T
      cells. These features are therefore consistent with previous work reporting an
      immature phenotype for lymphoid DCs in adult blood. The significance of the
      inverted CD11c+/CD11c- ratio observed in CB DCs (1:3) with respect to adult blood
      DCs (3:1) remains to be explained.

PMID- 11442486
TI  - Two further British families with the 'cryohydrocytosis' form of hereditary
      stomatocytosis.
AB  - We describe two families with the 'cryohydrocytosis' form of stomatocytosis. Both
      show a mild stomatocytic anaemia with Hb levels of 12-16 g/dl and reticulocyte
      counts of 4.3-24%, with very marked autohaemolysis at refrigerator temperatures
      and pseudohyperkalaemia as a result of loss of K from red cells on storage at
      room temperature. The ouabain + bumetanide-insensitive 'passive leak' K influx
      showed a 'U'-shaped temperature dependence, with a minimum at 23 degrees C. In
      one family, there was consistent variation in haematological severity within the
      pedigree. In the other, the parents of the proposita were normal, but all three
      of her children were affected, consistent with a new mutation of a dominant
      condition. Cold storage of the red cells led to a very marked increase in osmotic
      fragility and macrospherocytosis, explaining why a diagnosis of 'hereditary
      spherocytosis' can easily be reached in these pedigrees.

PMID- 11442487
TI  - Congenital sideroblastic anaemia successfully treated using allogeneic stem cell
      transplantation.
AB  - Therapy for patients with congenital sideroblastic anaemia has been limited to
      blood transfusions and chelation. Three children with congenital sideroblastic
      anaemia (SA) who were blood transfusion dependent underwent stem cell
      transplantation (SCT) from matched sibling donors. Conditioning consisted of
      cyclophosphamide 50 mg/kg/d for 4 d, busulphan 4 mg/kg/d for 4 d and anti
      thymocyte globulin (ATG) 30 mg/kg for four doses pretransplant. Graft-versus-host
      disease (GVHD) prophylaxis was with cyclosporin A and methotrexate. All patients
      engrafted, and are alive and transfusion independent. SCT can be curative for
      patients with SA.

PMID- 11442488
TI  - Irradiation enhances the support of haemopoietic cell transmigration,
      proliferation and differentiation by endothelial cells.
AB  - Endothelial cells (ECs) are a critical component of the bone marrow stroma in the
      regulation of haemopoiesis. Recovery of bone marrow aplasia after radiation
      exposure depends, in part, on the repair of radiation-induced endothelial damage.
      Therefore, we assessed the ability of an irradiated human bone marrow EC line
      (TrHBMEC) to support transmigration, proliferation and differentiation of CD34+
      bone marrow cells either irradiated or not in transendothelial migration or co
      culture models. Radiation-induced EC damage was reflected by an increased release
      of soluble intercellular adhesion molecule (sICAM)-1 and platelet endothelial
      cell adhesion molecule (PECAM)-1. Irradiation of TrHBMECs with a 10 Gy dose
      strongly enhanced the transmigration of CD34+ cells, granulo-monocytic
      progenitors (CFU-GM) and erythroid progenitors (BFU-E). While ICAM-1 and PECAM-1
      expression on irradiated TrHBMECs was increased, only antibodies against PECAM-1
      inhibited the radiation-induced enhanced transmigration of haemopoietic cells.
      Irradiation of TrHBMECs (5-15 Gy) also increased proliferation and
      differentiation towards the granulo-monocytic lineage of co-cultured CD34+ cells,
      as well as colony formation by those cells and the production of interleukin 6
      (IL-6), IL-8, granulocyte colony-stimulating factor (CSF) and granulocyte
      macrophage CSF. Irradiated TrHBMECs were more capable of stimulating irradiated
      (1,2 Gy) CD34+ cells and haemopoietic progenitors than non-irradiated TrHBMECs.
      Together, these results suggest that, despite the radiation-induced damage,
      irradiated ECs may favour haemopoietic reconstitution after radiation exposure.

PMID- 11442489
TI  - Accumulation of gamma-globin mRNA and induction of erythroid differentiation
      after treatment of human leukaemic K562 cells with tallimustine.
AB  - Human leukaemic K562 cells can be induced in vitro to erythroid differentiation
      by a variety of chemical compounds, including haemin, butyric acid, 5
      azacytidine, cytosine arabinoside, mithramycin and chromomycin, cisplatin and
      cisplatin analogues. Differentiation of K562 cells is associated with an increase
      of expression of embryo-fetal globin genes, such as the zeta-, epsilon- and gamma
      globin genes. The K562 cell line has been proposed as a very useful in vitro
      model system to determine the therapeutic potential of new differentiating
      compounds as well as to study the molecular mechanism(s) regulating changes in
      the expression of embryonic and fetal human globin genes. Inducers of erythroid
      differentiation stimulating gamma-globin synthesis could be considered for
      possible use in the therapy of haematological diseases associated with a failure
      in the expression of normal beta-globin genes. We have analysed the effects of
      tallimustine and distamycin on cell growth and differentiation of K562 cells. The
      results demonstrated that tallimustine is a potent inducer, while distamycin is a
      weak inducer, of K562 cell erythroid differentiation. Erythroid differentiation
      was associated with an increase of accumulation of gamma-globin mRNA and of
      production of both haemoglobin (Hb) Gower 1 and Hb Portland. In addition,
      tallimustine-mediated erythroid induction occurred in the presence of activation
      of the apoptotic pathway. The reasons for proposing tallimustine as an inducer of
      gamma-globin gene expression are strongly sustained by the finding that this
      compound stimulates fetal haemoglobin production in human erythroid precursor
      cells from normal subjects.

PMID- 11442490
TI  - Short-term phytohaemagglutinin-activated mononuclear cells induce endothelial
      progenitor cells from cord blood CD34+ cells.
AB  - Endothelial progenitor cells (EPCs) were recently demonstrated to exist in human
      cord blood. Phytohaemagglutinin (PHA), a potent mitogen for mononuclear cells was
      used to induce EPCs from unsorted cord blood mononuclear cells (CBMCs). Adherent
      cells in clusters appeared approximately 24 h after CBMCs were cultured in plain
      Roswell Park Memorial Institute media containing 10% fetal bovine serum (culture
      media) and PHA. Adherent cells were further propagated for 1 week in plain
      culture media. Flow cytometry and Di-I staining analyses showed that CD45-,
      CD34+, Flk-1+, CD31+ or VE-cadherin+ EPCs were induced and that they were mainly
      from the CD34+ cell compartment. When enriched CD34+ cells alone were stimulated
      with culture supernatant of the PHA-activated CBMCs, they neither proliferated
      readily nor induced EPCs. Because EPCs first appeared within the clustering cells
      that expressed high levels of fibronectin and vascular endothelial growth factor
      (VEGF), our data suggest that both cell-cell/cell-matrix interaction and the
      local VEGF action are important in the induction of EPCs. Thus, we demonstrate
      for the first time that EPCs are induced from human cord blood stem cell
      populations that interact with neighbouring PHA-activated CBMCs. This finding may
      have a significant implication in inflammatory cell-mediated vasculogenesis and
      angiogenesis in vivo.

PMID- 11442491
TI  - A cautionary tale: how to delete mouse haemopoietic stem cells with busulphan.
AB  - In this study treating mice with the 'correct' dose of busulphan did not
      necessarily destroy all haematopoietic stem cells. In certain circumstances host
      stem cells survived undetected and subsequently resumed haemopoiesis. This may
      apply to the use of busulphan clinically. We found that the following conditions
      determined the deletion of mouse stem cells using busulphan: (1) graft size-
      grafting more than 106 marrow cells ( approximately 0.3% of the animal's stem
      cells) concealed the survival of stem cells; (2) dose of busulphan--insufficient
      busulphan did not kill all host stem cells; (3) old or improperly stored
      busulphan failed to delete all host stem cells; furthermore (4) the survival of
      host stem cells should be assessed by typing many kinds of circulating cells; and
      (5) tests should be carried out to determine if busulphan has killed all host
      stem cells by typing circulating blood cells at appropriate intervals.

PMID- 11442492
TI  - Proliferative activity of leukaemic blasts and cytosine arabinoside
      pharmacodynamics are associated with cytogenetically defined prognostic subgroups
      in acute myeloid leukaemia.
AB  - The biological mechanisms responsible for the association of specific karyotypes
      with prognosis in acute myeloid leukaemia (AML) remain largely unclear. A
      prospective study was performed to evaluate how far cytogenetically defined
      prognostic subgroups of AML differ in their proliferative activity as a potential
      mechanism for differential sensitivities to S-phase-specific induction
      chemotherapy comprising cytosine arabinoside (AraC). One hundred and eighty-seven
      patients with de novo AML were included in the study; 25 patients with a
      favourable [inv(16), t(8;21), t(15;17)] karyotype, 99 with a normal karyotype, 29
      with an unfavourable karyotype (-5, 5q-, -7, 7q-, complex aberrations) and 34
      with cytogenetic aberrations of unknown prognostic significance (all others). The
      favourable group demonstrated the highest ex vivo proliferative activity (PA)
      (3.41 pmol/105 cells), significantly (P = 0.02) exceeding the unfavourable group
      with the lowest PA (0.72) and the group with a normal karyotype (1.06) or with
      karyotype of unknown significance (1.05) that both demonstrated an intermediate
      PA. Samples with a high PA (> median of the whole group) were more likely to
      produce interleukin 3, granulocyte macrophage colony-stimulating factor (GM-CSF),
      granulocyte CSF (G-CSF) (56%, 43% and 50%) than cells with a low PA (33%, 36% and
      36%; n.s.). The effect of priming by exogenous GM-CSF or G-CSF was significantly
      more pronounced in samples with a low PA than in rapidly proliferating samples (P
      < 0.01). For the whole group, a high PA was closely associated with an increased
      incorporation of AraC triphosphate (AraCTP) into the DNA (P < 0.0001).
      Clinically, a high PA was associated with a better complete remission (CR) rate
      in the normal (95% versus 62%) and the unfavourable group (75% versus 33%). The
      significant differences in proliferative activity between cytogenetic subgroups
      of AML are associated with increased cytosine arabinoside pharmacodynamics and
      constitute one potential mechanism for the different response of cytogenetic
      subgroups to AraC-based induction therapy.

PMID- 11442493
TI  - Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia.
AB  - Genomic DNA from 97 cases of adult de novo acute myeloid leukaemia (AML) was
      screened using polymerase chain reaction (PCR) and conformation-sensitive gel
      electrophoresis (CSGE) for FLT3 exon 20 mutations. Initial sequencing of four
      cases, representing the spectrum of CSGE abnormalities, revealed changes
      affecting codon Asp835 in three cases and also an intron 20 A to G change. In
      order to identify all possible Asp835 alterations, as well as the frequency of
      the intronic change nucleotide 2541 + 57 A-->G, the patient PCR products were
      digested with EcoRV and NlaIII respectively. Seven cases (7.2%) possessed a
      mutation affecting Asp835; these were identified, following DNA sequencing, as
      Asp835Tyr (n = 5), Asp835His (n = 1) and Asp835del (n = 1). Alterations affecting
      Asp835 were not found in 80 normal control DNA samples. In contrast, the
      nucleotide 2541 + 57 A-->G change was shown to be a polymorphism, with an allelic
      frequency of 0.24 for the G and 0.76 for the A allele. This study reports, for
      the first time, point mutations in the human FLT3 gene that, because of their
      homology with other class III receptor tyrosine kinase mutations, probably result
      in constitutive activation of the receptor.

PMID- 11442494
TI  - Intercellular adhesion molecule-1 in extravasation of normal mononuclear and
      leukaemia cells.
AB  - Interaction of intercellular adhesion molecules (ICAMs) with their receptors has
      a key role in normal leucocyte adhesion and migration, whereas in leukaemia this
      has not been well established. In this study, we have evaluated the roles of
      different adhesion molecules in normal and leukaemia cell extravasation in a
      novel organotypic model for vessel wall and measured plasma ICAM-1 and -2 levels
      in acute leukaemia patients at diagnosis and during chemotherapy. We found that
      both normal mononuclear cells and blast cells from acute leukaemia patients, as
      well as retinoic acid-treated promyelocytic leukaemia cells, rapidly extravasated
      through endothelial cell layers into the underlying collagen matrix. ICAM-1
      antibody prevented the extravasation, while antibodies to other adhesion
      molecules showed little (CD18, ICAM-2) or no inhibition (CD11a and ICAM-3).
      Soluble ICAM-1 (sICAM-1) protein had no effect. We also observed increased plasma
      sICAM-1 and -2 levels in leukaemia patients and found that they correlated only
      weakly with the white blood cell count. No correlation was found between sICAM-1
      or -2 levels and the response to therapy. Although elevated sICAM-2 levels
      decreased rapidly during chemotherapy, sICAM-1 levels did not. Because sICAM-1
      protein had no effect on leukaemia cell extravasation in vitro, it is probable
      that the increased plasma sICAM-1 levels in leukaemia patients may not play a
      role in leukaemia cell infiltration. However, as we showed that ICAM-1 mediated
      leukaemia cell extravasation on the cell surface, it is possible that cellular
      ICAM-1 has an important role in disease progression.

PMID- 11442495
TI  - Analysis of Vgamma/Jbeta trans-rearrangements in paediatric patients undergoing
      chemotherapy.
AB  - The frequency of the hybrid Vgamma/Jbeta trans-rearrangement in peripheral blood
      lymphocytes (PBLs) was analysed in a transversal study of paediatric patients (n
      = 210) with acute lymphoblastic leukaemia (ALL) and solid tumours (ST). Different
      amounts of DNA were used as the template for a nested polymerase chain reaction
      to evaluate the frequency of hybrid Vgamma/Jbeta genes, using silver-stained
      gels. The frequency of the rearrangement was evaluated in groups before, during
      and after therapy. A greatly increased frequency of Vgamma/Jbeta trans
      rearrangement was found in PBLs of both groups of patients during exposure to
      chemotherapeutic agents compared with patients before chemotherapy. In patients
      who had finished treatment, the frequency of the rearrangement fell promptly to
      the baseline levels in ST but showed a slow decrease in ALL in those in whom
      increased levels could be found until 4 years after the end of treatment. We
      hypothesize that the chemotherapeutic agents are able to induce the Vgamma/Jbeta
      trans-rearrangement, but this is transient in most cases. The exact relationship
      between the persistence of the rearrangement and the occurrence of secondary
      leukaemia remains to be determined.

PMID- 11442496
TI  - In vitro induction of apoptosis for nasal angiocentric natural killer cell
      lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A.
AB  - Epstein-Barr virus (EBV)-associated nasal T/natural killer (NK) cell lymphoma has
      often been reported in Asian countries and has been recently confirmed as a novel
      clinicopathological entity. The prognosis of advanced stage disease is quite poor
      and an effective chemotherapeutic modality is strongly advocated. We have
      established the novel cell line NK-YS, which preserves the original
      characteristics of EBV-associated nasal angiocentric T/NK cell lymphoma. Using
      this cell line, we investigated the induction of apoptosis by apoptosis-inducing
      agents, and expression of P-glycoprotein (P-gp), p53 and bcl-2 proteins. NK-YS
      showed resistance towards apoptosis-inducing agents and expressed bcl-2 and P-gp
      but not p53. To overcome this drug resistance, we added cyclosporine A (CsA) and
      these agents to culture media as a P-gp antagonist. The combination of CsA and
      etoposide or CsA and doxorubicin induced apoptotic cell death. These results
      indicated that P-gp-mediated drug resistance is an essential mechanism of drug
      resistance of the NK-YS cell line. Combined therapy of conventional anti-cancer
      agents with CsA may have an important place in the establishment of a curative
      therapy for disseminated nasal angiocentric NK cell lymphoma.

PMID- 11442497
TI  - Cost-effectiveness of high-dose chemotherapy in first-line treatment of advanced
      multiple myeloma.
AB  - The cost-effectiveness of high-dose chemotherapy in multiple myeloma was
      considered as part of a UK National Health Service Executive regional evidence
      based appraisal process. The use of high-dose chemotherapy supported by
      autologous stem cell transplantation in patients under 65 years of age was shown
      to provide a marginal benefit of 0.7 life-years over conventional chemotherapy.
      This corresponded to an incremental cost 'per life-year gained' figure of
      approximately pound15 000, based upon initial treatment costs and trial-period
      data only. The use of high-dose chemotherapy in the first-line treatment of
      advanced multiple myeloma improves event-free and overall survival and appears to
      be a cost-effective treatment option.

PMID- 11442498
TI  - Interferon as therapy for multiple myeloma: an individual patient data overview
      of 24 randomized trials and 4012 patients.
AB  - Many randomized trials have evaluated alpha-interferon as myeloma therapy, some
      suggesting a benefit and others not. Most were too small to give reliable
      answers, so a systematic overview has been performed to provide a more reliable
      estimate of the effect of interferon. The main end-points were response rates
      (induction trials), progression-free survival (PFS) and overall survival (OS).
      Individual patient data were supplied for 24 trials involving 4012 patients, 12
      induction trials (2469 patients) and 12 maintenance trials (1543 patients). In
      induction, response rates were slightly better with interferon (57.5% versus
      53.1%, P = 0.01). PFS was better with interferon (33% versus 24% at 3 years, P <
      0.00001), an effect seen in both induction (P = 0.0003) and maintenance (P <
      0.00001) trials. Median time to progression was increased by about 6 months in
      both settings. OS was somewhat better with interferon (53% versus 49% at 3 years,
      P = 0.01) with median survival increased by about 4 months. This benefit was
      restricted to the smaller trials. The effect of interferon was not significantly
      related to the dose or duration of interferon or to patients' characteristics.
      PFS was improved with interferon, but the survival benefit, if any, was small and
      needs balancing against cost and toxicity.

PMID- 11442499
TI  - Long-term follow-up of a prospective, double-blind, placebo-controlled randomized
      trial of clodronate in multiple myeloma.
AB  - Oral clodronate (1600 mg/d) has been shown to significantly reduce the incidence
      of skeletal complications in multiple myeloma. Preliminary analysis of a double
      blind placebo-controlled trial of this treatment indicated that clodronate might
      prolong survival in patients without vertebral fractures at presentation. This
      issue was re-examined after further follow-up of the patients recruited into the
      Medical Research Council (MRC) VIth Myeloma Study. The trial examined the effects
      of clodronate on the natural history of skeletal disease in multiple myeloma; 619
      patients were randomized between June 1986 and May 1992 commencing 15 d after the
      start of ABCM [adriamycin, BCNU (carmustine), cyclophosphamide, melphalan]
      chemotherapy or 43 d after ABCMP (ABCM + prenisolone); 535 patients who received
      clodronate or placebo were included in the analysis. The presence or absence of
      spinal fractures was assessed centrally from spinal X-rays; long-bone fractures
      were assessed locally. With a median follow-up of 8.6 years, there was no overall
      significant difference in survival between the two treatment groups (O/E, chi2 =
      0.78, P = 0.38). Among the subgroup of 153 patients with no skeletal fractures at
      presentation there was a significant survival advantage (O/E, chi2 = 7.52, P =
      0.006) in favour of the 73 patients receiving clodronate, with median survivals
      being, respectively, 59 months (95% CI 43-71 months) and 37 months (95% CI 31-52
      months), and 5-year survivals being 46% and 35%. The original analysis of this
      study shows that there is a benefit in taking 1600 mg clodronate daily for
      patients with myelomatosis to prevent the development of new skeletal disease.
      Bearing in mind the limitations of subgroup analysis, the present study indicates
      that treatment may prolong survival in patients without overt skeletal disease at
      diagnosis. These observations, however, require confirmation in prospective
      clinical trials.

PMID- 11442500
TI  - A modified high-dose dexamethasone regimen for primary systemic (AL) amyloidosis.
AB  - High-dose dexamethasone (HD-Dex) has been reported to benefit AL amyloidosis
      patients with varying response rates. Our preliminary experience with the usual
      HD-Dex schedule indicated that the induction phase was rather toxic in AL
      patients. We therefore adopted a milder schedule consisting of dexamethasone 40
      mg on d 1-4 q21 d for up to eight cycles. Overall 8 out of 23 (35%) treated
      patients responded to treatment in a median time of 4 months (range 2-6 months)
      without significant toxicity. This regimen may be considered front-line therapy
      when autologous stem cell transplantation is not feasible and when a rapid
      response is particularly important.

PMID- 11442501
TI  - True histiocytic lymphoma following B-acute lymphoblastic leukaemia: case report
      with evidence for a common clonal origin in both neoplasms.
AB  - True histiocytic lymphoma (THL) is a very rare type of non-Hodgkin's lymphoma
      (NHL) in which neoplastic cells exhibit markers of histiocytic differentiation.
      Some cases of THL have been reported in patients with previous acute
      lymphoblastic leukaemia (ALL), especially in children and young adults, in whom
      the acute leukaemia was of T-cell origin. The relationship between the initial
      lymphoid tumour and the secondary THL remains unclear, as a common monoclonal
      origin shared by both neoplasms has never been definitively demonstrated. We
      report a patient with B-ALL who developed a nodal and extranodal tumour with
      histological and immunohistochemical features of THL 4 years after the initial
      diagnosis. Genotypic study showed that both neoplasms contained the same
      immunoglobulin heavy gene rearrangement, which has not been reported previously.

PMID- 11442502
TI  - Severe and long-lasting disruption of T-cell receptor diversity in human myeloma
      after high-dose chemotherapy and autologous peripheral blood progenitor cell
      infusion.
AB  - Vaccine-based strategies are currently under investigation as a means of inducing
      tumour-specific immune responses and improving the clinical outcome of multiple
      myeloma (MM) patients in remission after high-dose chemotherapy and peripheral
      blood progenitor cell (PBPC) infusion. The immune competence of these patients
      was investigated by determining the overall diversity of the T-cell receptor
      (TCR) repertoire in the peripheral blood (PB) and bone marrow (BM). The average
      time after transplantation was 13 months. The clonality and reciprocal usage of
      BV gene segments (TCRBV repertoire) was estimated at the cDNA level and membrane
      protein expression. The TCRBV repertoire of MM was severely disrupted compared
      with age-matched normal donors. On average, one-third of the total repertoire in
      both the PB and the BM consisted of T cells expressing oligoclonal TCRbeta
      transcripts. Flow cytometry showed an increased frequency of abnormally expanded
      BV subfamilies at both sites. BV expansions were predominantly CD8+ and had the
      phenotype of antigen-experienced memory T cells as well as T cells with the naive
      phenotype. Oligoclonality was not restricted to phenotypically expanded BV
      subfamilies, but also involved normally represented BV subfamilies. The TCR
      repertoire of MM in remission was then compared with monoclonal gammopathy of
      undetermined significance (MGUS) and MM patients at diagnosis. The degree of TCR
      diversity was similar in age-matched normal donors and MGUS, but progressively
      decreased from MGUS to MM at diagnosis and then to MM in remission. These data
      indicate that: (1) there is a long-lasting and severe disruption of TCR diversity
      after high-dose chemotherapy and PBPC infusion, and (2) the extent of TCR
      disruption may affect the clinical outcome of vaccine-based strategies delivered
      at the stage of minimal residual disease.

PMID- 11442503
TI  - Patient cytomegalovirus seropositivity with or without reactivation is the most
      important prognostic factor for survival and treatment-related mortality in stem
      cell transplantation from unrelated donors using pretransplant in vivo T-cell
      depletion with anti-thymocyte globulin.
AB  - We evaluated the cytomegalovirus (CMV) serostatus as a risk factor for survival
      and treatment-related mortality (TRM) in 125 patients allografted from an
      unrelated donor between 1994 and 1999. All patients received pretransplant in
      vivo T-cell depletion using rabbit anti-thymocyte globulin (ATG). Only one
      patient had primary graft failure and severe grade III/IV graft-versus-host
      disease occurred in 14% of the patients. The overall survival (OS) at 3 years was
      70% for CMV-negative patients (n = 76) and 29% in the seropositive cohort (n =
      49) (P > 0.001). In multivariate analyses, CMV seropositivity remained an
      independent negative prognostic factor for OS (RR: 2.1; CI: 1.2-3.8; P = 0.014),
      apart from age > 20 years (RR: 2.74; CI: 1.2-3.8; P = 0.004) and late leucocyte
      engraftment (RR: 2.4; CI: 1.2-4.9; P = 0.015). The TRM for all patients was 27%.
      Despite monitoring for CMV antigenaemia and preemptive therapy with ganciclovir
      when reactivation occurred, seropositive patients had a three times higher risk
      of fatal treatment-related complications than seronegative patients. In
      multivariate analyses, CMV seropositivity remained the strongest independent
      negative factor for TRM (RR: 5.3; CI: 1.9-14.6; P = 0.002), followed by age > 20
      years (RR: 4.8; CI: 1.3-18.1; P = 0.02) and delayed leucocyte engraftment (RR:
      3.6; CI: 1.2-11; P = 0.02). The TRM was identical in seropositive patients with
      (n = 27) or without (n = 22) CMV reactivation (44% versus 50%). We conclude that
      CMV seropositivity, despite preemptive ganciclovir therapy and even without
      reactivation, is a major negative prognostic factor for survival as well as for
      TRM in unrelated stem cell transplantation using pretransplant in vivo T-cell
      depletion with ATG.

PMID- 11442504
TI  - Estimating the relapse stage in chronic myeloid leukaemia patients after
      allogeneic stem cell transplantation by the amount of BCR-ABL fusion transcripts
      detected using a new real-time polymerase chain reaction method.
AB  - We have used a new single-step real-time reverse transcription polymerase chain
      reaction (RT-PCR) method to quantify BCR-ABL transcripts, thereby estimating the
      relapse stage in chronic myeloid leukaemia patients after allogeneic transplants.
      In 402 samples from 172 patients, BCR-ABL expression was determined and
      normalized, using the GAPDH housekeeping gene product as an endogenous reference.
      In our real-time RT-PCR assay, serial dilutions of RNA of the K562 cell line
      remained positive down to 7.5 pg. The median normalized BCR-ABL amount differed
      significantly (P < 0.001) between the various disease stages and was 0.06% (range
      0.001-1.55%), 3.2% (range 1.4-5.6%) and 21.5% (range 6.8 -827%) in 17 patients
      with a molecular relapse, in eight patients with a cytogenetic relapse and in 10
      patients with a haematological relapse respectively.

PMID- 11442505
TI  - Genomic structure of human FLT3: implications for mutational analysis.

PMID- 11442506
TI  - Serendipity and the use of random donor platelets in fetomaternal alloimmune
      thrombocytopenia (FMAIT).

PMID- 11442507
TI  - Priming of neutrophil function in the newborn.

PMID- 11442509
TI  - TEL/MN1 fusion in a de novo acute myeloid leukaemia-M2 patient who showed strong
      resistance to treatment.

PMID- 11442510
TI  - The contribution of F. W. Peabody to the study of pernicious anaemia.

PMID- 11442511
TI  - Low frequency of reverse transcription polymerase chain reaction-detectable
      chromosome aberrations in relapsed acute myeloid leukaemia: implications for
      detection of minimal residual disease.

PMID- 11442512
TI  - Antenatal testing for haemoglobinopathies.

PMID- 11442513
TI  - Clinical monitoring after cessation of enzyme replacement therapy in M. Gaucher.

PMID- 11442515
TI  - Interruption in enzyme replacement therapy for Gaucher disease.

PMID- 11442517
TI  - Effects of imilglucerase withdrawal on an adult with Gaucher disease.

PMID- 11442518
TI  - Ethics of surgical innovation.

PMID- 11442519
TI  - Medical negligence and the law.

PMID- 11442520
TI  - Systematic review and meta-analysis of emergency ultrasonography for blunt
      abdominal trauma.
AB  - BACKGROUND: How precise and reliable is ultrasonography as a primary tool for
      injury assessment in blunt abdominal trauma? METHODS: A systematic review and
      meta-analysis were conducted of prospective clinical trials of ultrasonography
      for blunt abdominal trauma. Publications were retrieved by structured searching
      among databases, review articles and major text books. Authors and experts in the
      field were contacted for original and unpublished data. For statistical analysis,
      summary receiver operating characteristic curves (SROCs) were computed using
      weighted and robust regression models, with Q* denoting the shoulder of the
      curve. Post-test probabilities were calculated as a function of pooled likelihood
      ratios (LRs). RESULTS: Thirty of 123 trials enrolling 9047 patients were eligible
      for final analysis. With respect to targeting organ lesions, ultrasonography
      showed a summary Q* value of 0.91 (inverse variance weights, 95 per cent
      confidence interval (c.i.) 0.76-1.07); negative predictive values ranged from
      0.72 to 0.99. A similar SROC slope was calculated for screening for free fluid
      (Q* = 0.89 (95 per cent c.i. 0.73-1.05)). Ultrasonography detects the presence of
      organ lesions, but fails to exclude abdominal injuries (random effects negative
      LR 0.23 (95 per cent c.i. 0.18-0.28)). Given a pretest probability of 50 per cent
      for blunt abdominal injury, a post-test probability of nearly 25 per cent remains
      in the case of a negative sonogram. CONCLUSION: Despite its high specificity,
      ultrasonography has an unexpectedly low sensitivity for the detection of both
      free fluid and organ lesions. In clinically suspected abdominal trauma, another
      assessment (e.g. helical computed tomography) must be performed regardless of the
      initial ultrasonographic findings.

PMID- 11442521
TI  - Meta-analysis of low molecular weight heparin in the prevention of venous
      thromboembolism in general surgery.
AB  - BACKGROUND: Low molecular weight heparins (LMWHs) have become routine
      thromboprophylaxis in general surgery. However, their actual clinical effect, its
      magnitude relative to that of unfractionated heparin (UFH), and the optimal dose
      are still debated. METHODS: A meta-analysis was performed of all available
      randomized trials in general surgery comparing LMWH with placebo or no treatment,
      or with UFH. RESULTS: Comparison versus placebo or no treatment confirmed that
      the significant reduction in asymptomatic deep vein thrombosis (DVT) obtained
      with LMWH (n = 513; relative risk (RR) 0.28 (95 per cent confidence interval 0.14
      0.54)) was associated with a significant reduction in clinical pulmonary embolism
      (n = 5456; RR 0.25 (0.08-0.79)) and clinical venous thromboembolism (VTE) (n =
      4890; RR 0.29 (0.11-0.73)), and a trend towards a reduction in overall mortality
      rate. Comparison versus UFH showed a trend in favour of LMWH, with a significant
      reduction in clinical VTE (P = 0.049), a trend also found for cancer surgery.
      LMWH at doses below 3400 anti-Xa units seemed to be as effective as, and safer
      than, UFH, while higher doses yielded slightly superior efficacy but increased
      haemorrhagic risk, including that of major haemorrhage. CONCLUSION: Asymptomatic
      DVT may be regarded as a reliable surrogate endpoint for clinical outcome in
      studies investigating thromboprophylaxis in general surgery. LMWH seems to be as
      effective and safe as UFH. Determination of the optimal dose regimen of LMWH for
      this indication requires further investigation.

PMID- 11442522
TI  - Prospective randomized trial of polypropylene mesh compared with nylon darn in
      inguinal hernia repair.
AB  - BACKGROUND: The main aim of this study was to evaluate outcome in patients
      undergoing open inguinal hernia repair with either polypropylene mesh or nylon
      darn. METHODS: This was a randomized prospective trial of patients who underwent
      the procedure with follow-up at 1 week, 6 weeks and 1 year. RESULTS: One hundred
      men underwent 105 repairs by consultant surgeons and registrars; there were 54
      mesh and 51 nylon repairs. Demographics in both groups were similar at the start
      of the trial, as were the types of hernia. The pain scores at 24, 48 and 72 h
      were similar, as was the duration of analgesia requirement. There were no
      differences in early or late complications. Return to normal activity in each
      group was also similar, with a mean time of 5 weeks. The recurrence rate in both
      groups was comparable: 4 per cent after mesh repair and 4 per cent after darn
      repair at 1-year review. CONCLUSION: Open inguinal hernia repair with a nylon
      darn was equivalent to polypropylene mesh with respect to early measures of
      postoperative outcome and recurrence at 1 year.

PMID- 11442523
TI  - Provocation of experimental aortic inflammation and dilatation by inflammatory
      mediators and Chlamydia pneumoniae.
AB  - BACKGROUND: The macrophage appears to have a key role in the inflammation and
      proteolysis associated with the growth and development of abdominal aortic
      aneurysms. The role of inflammatory mediators and Chlamydia pneumoniae in
      stimulating the influx of macrophages and dilatation of the abdominal aorta was
      investigated in an experimental model. METHODS: Periaortic application of calcium
      chloride solution (and monocyte chemoattractant protein (MCP) 1, a cocktail of
      cytokines or C. pneumoniae) to the abdominal aorta of New Zealand White rabbits
      was performed at laparotomy. Some animals were fed a cholesterol-rich diet. The
      diameter of the aorta was measured by ultrasonography and after perfusion
      fixation, 3 weeks after laparotomy. Aortic sections were stained with RAM-11 to
      identify macrophages for counting. The presence of C. pneumoniae DNA was
      confirmed using the polymerase chain reaction. RESULTS: Aortic macrophage influx
      in response to MCP-1, thioglycollate or C. pneumoniae was more than doubled in
      the cholesterol-fed animals. In response to human recombinant MCP-1 (1 microg)
      the mean(s.d.) macrophage count increased from 79(19) to 340(215) per unit area
      (P < 0.02). Even in cholesterol-fed animals, application of MCP-1 (recombinant
      human or rabbit form) was not associated with aortic dilatation. Application of
      thioglycollate 0.1 mol/l, or live or formalin-inactivated C. pneumoniae (0.5 x
      108 organisms), was associated with a similar increase in macrophages to that
      caused by MCP-1 and a significant (approximately twofold) increase in aortic
      diameter after 3 weeks. CONCLUSION: Macrophage influx into rabbit abdominal
      aorta, without macrophage activation, is insufficient to cause experimental
      aortic dilatation. C. pneumoniae antigens appeared to stimulate aortic
      dilatation, probably by specific activation of macrophages.

PMID- 11442524
TI  - A single normal ultrasonographic scan at age 65 years rules out significant
      aneurysm disease for life in men.
AB  - BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has been carried out in
      Gloucestershire since 1990. All men in the county are offered aortic
      ultrasonography in their 65th year. Men with an aortic diameter of less than 26
      mm are considered 'normal' and no follow-up is arranged. The aim of this study
      was to ascertain if men with 'normal' aortic diameters at age 65 years ever
      develop a clinically significant aneurysm. METHODS: A cohort study was performed
      on 223 65-year-old men who had an aorta of less than 26 mm in diameter in 1988.
      These men had repeat ultrasonography in 1993 and 2000. The causes of death in men
      who died during this interval were investigated. RESULTS: Eight men were lost to
      follow-up. As far as it was possible to ascertain, none of the 86 men who died
      over the 12-year interval did so from ruptured AAA. There was no clinically
      significant increase in mean aortic diameter in the remaining 129 men who had
      three serial ultrasonographic scans over the 12-year interval. CONCLUSION: A
      single, 'normal' ultrasound scan at age 65 years effectively rules out the risk
      of clinically significant aneurysm disease for life in men.

PMID- 11442525
TI  - Association between plaque instability, angiogenesis and symptomatic carotid
      occlusive disease.
AB  - BACKGROUND: Angiogenesis is a recognized feature of the atherosclerotic process
      and has been described in the context of unstable coronary atherosclerotic
      lesions. The aim of this study was to assess the association between angiogenesis
      in atherosclerotic carotid plaques and microscopic features of plaque
      instability, in particular intraplaque haemorrhage. METHODS: Consecutive patients
      undergoing carotid endarterectomy were included. Endarterectomy specimens were
      divided into their constituent atherosclerotic lesions. Histological sections
      were prepared and stained with haematoxylin and eosin, and immunohistochemically
      with an endothelial cell marker (CD34). The quantity of intraplaque haemorrhage
      was measured in transverse histological sections using computerized image
      analysis. Microvessel counts were performed in CD34-stained sections and were
      verified through computerized image analysis. RESULTS: Some 239 atherosclerotic
      lesions from 73 patients were available for analysis; 73 were early lesions, 74
      were raised fibroatheromas and 92 were unstable atherosclerotic plaques. One
      hundred and fifty lesions were not haemorrhagic; 89 exhibited intraplaque
      haemorrhage, of which 28 involved less than 50 per cent of the plaque sectional
      area. There were higher microvessel counts in plaques containing over 50 per cent
      haemorrhage (P < 0.0001), unstable atherosclerotic lesions (P < 0.0001) and
      atherosclerotic lesions obtained from symptomatic patients (P < 0.001).
      CONCLUSION: There are strong associations between plaque vascularity, quantity of
      intraplaque haemorrhage and presence of symptomatic carotid occlusive disease.

PMID- 11442526
TI  - Differences in the detection of cyclo-oxygenase 1 and 2 proteins in symptomatic
      and asymptomatic carotid plaques.
AB  - BACKGROUND: The expression of cyclo-oxygenase (COX) 1 and 2 has been demonstrated
      in atherosclerotic arteries. In the present study this was correlated with
      symptoms arising from a carotid plaque. METHODS: Carotid plaques from 12
      asymptomatic patients were compared with 11 plaques from patients who had had
      neurological symptoms within the preceding 30 days. Sections were stained with
      haematoxylin and eosin, elastin van Gieson and goat antihuman antibodies to COX-1
      and COX-2. Plaque morphology was correlated with neurological symptoms. The area
      with positive COX-1 and COX-2 staining was measured by computerized planimetry in
      entire cross-sections and in specific areas of the plaque. RESULTS: There was a
      significant association between cap thinning and plaque rupture with symptoms (P
      = 0.003). The percentage area of positive staining in entire cross-sections for
      both COX-1 and COX-2 was significantly greater in symptomatic plaques (P = 0.001
      and 0.0004 respectively). Staining in symptomatic plaques was significantly
      greater in the cap (COX-1: P = 0.001; COX-2: P = 0.0001) and shoulder (COX-1: P =
      0.008; COX-2: P = 0.007) regions of the plaque. COX-1 expression in the sclerotic
      area was not increased (P = 0.15) although COX-2 staining was significantly
      greater (P = 0.04). CONCLUSION: Both COX-1 and COX-2 detection was increased in
      symptomatic plaques. COX may contribute to plaque rupture and the onset of
      symptoms.

PMID- 11442527
TI  - Portsmouth POSSUM models for abdominal aortic aneurysm surgery.
AB  - BACKGROUND: The Portsmouth Physiological and Operative Severity Score for
      enUmeration of Mortality and morbidity (P-POSSUM) equation permits comparative
      audit that allows for differences in case mix. The methodology has previously
      been shown accurately to model general surgical and vascular surgical patients.
      Patients with a ruptured abdominal aortic aneurysm (AAA) are, however, very
      different from elective patients and it may be hypothesized that they require
      their own specific risk model. METHODS: POSSUM data on 444 (213 emergency, 231
      elective) admissions for AAA surgery between August 1993 and July 2000 were
      analysed using the P-POSSUM equation for general surgery and the P-POSSUM
      equations developed for vascular surgery. RESULTS: All equations successfully
      modelled the elective aneurysms but failed to fit the emergency aneurysms, and
      the elective and emergency aneurysms combined. This suggested that admission
      method (not a POSSUM data item) is an important factor for patients with AAA.
      However, with these data it was not possible to generate a model, including
      admission method, that successfully modelled the combined elective and emergency
      data. The 213 emergency aneurysm repairs were divided into two groups by
      operation date. The first 106 (training set) were used to form logistic
      regression models following the P-POSSUM methodology. These models were found
      successfully to fit the remaining 107 records (test set) on prospective
      application (chi2 = 4.50, 4 d.f., P = 0.345). CONCLUSION: Ruptured AAAs appear to
      be different from elective AAAs and other vascular cases and require their own
      risk model.

PMID- 11442528
TI  - Performance indicators from routine hospital data: death following aortic surgery
      as a potential measure of quality of care.
AB  - BACKGROUND: There is increasing pressure to monitor surgical performance. In the
      UK, the Department of Health has produced clinical indicators based on routine
      data to monitor performance. This study analysed whether such data could measure
      performance in aortic surgery. METHODS: Routine hospital data on postoperative
      mortality were collected for 1995-1997 in the Trent region. Procedural and
      diagnostic codes, modes of admission, districts of residence, treatment and
      specialty data were compared with audit data and the Operating Theatre
      Information System. RESULTS: Inaccuracies in the Health Resource Group (HRG)
      codes meant that 21.4 per cent of elective aortic cases (HRG Q02) were probably
      emergencies and 26 per cent of probable ruptured aneurysms were not coded as a
      vascular emergency. Case mix and patient selection introduced a bias, apparent
      between tertiary and district general hospitals. For patients aged over 80 years,
      two district hospitals undertook no elective aortic surgery; the rate for
      emergency aortic surgery varied between 16 and 25 per cent in the district
      hospitals, and was 77 per cent in the tertiary centre. CONCLUSION: Crude
      mortality rates used as an indicator of performance are subject to bias and
      distortion owing to the collection of incorrect information, variation in patient
      selection between hospitals and case-mix differences. There was a considerable
      variation in selection and outcomes of patients undergoing aortic surgery in this
      study.

PMID- 11442529
TI  - Clinicopathological factors predicting outcome after resection of mass-forming
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The prognosis for patients with intrahepatic cholangiocarcinoma
      differs according to macroscopic type. The identification of clinical and
      pathological features that predict outcome in patients with mass-forming
      intrahepatic cholangiocarcinoma is required in order to determine optimal
      surgical strategies for patients with this type of tumour. METHODS: The details
      of 35 patients with resected mass-forming intrahepatic cholangiocarcinomas were
      analysed retrospectively. Univariate analysis of potential prognostic factors was
      performed. RESULTS: The cumulative survival rate at 1, 3 and 5 years after
      operation was 58, 33 and 33 per cent respectively. Patients with stage II tumours
      had a better outcome than those with advanced stage tumours. By univariate
      analysis, lymphatic invasion, lymph node metastasis, intrahepatic satellite
      lesions and microscopic resection margin involvement were found to be highly
      significant variables and were identified as possible risk factors for a poor
      outcome after operation. CONCLUSION: When frozen-section examination of lymph
      nodes reveals negative nodal metastasis, extensive anatomical hepatic resection
      is indicated for mass-forming intrahepatic cholangiocarcinomas. Intraoperative
      frozen-section examination of the resection margin to confirm the absence of
      cancer cells is recommended.

PMID- 11442530
TI  - Late mortality in patients with severe acute pancreatitis.
AB  - BACKGROUND: Mortality due to severe or necrotizing acute pancreatitis most often
      results from multiorgan dysfunction syndrome (MODS) occurring either early
      (within the first 14 days) or 2 weeks or more after the onset of symptoms due to
      septic complications. The aim of this study was to analyse the course of the
      disease in patients who died from severe acute pancreatitis. METHODS: Between
      January 1994 and August 2000 details of 263 consecutive patients with acute
      pancreatitis were entered prospectively into a database. All patients were
      treated in an intermediate or intensive care unit. RESULTS: The overall mortality
      rate was 4 per cent (ten of 263 patients). The mortality rate was 9 per cent (ten
      of 106) in patients with necrotizing disease. No patient died within the first 2
      weeks of disease onset. The median day of death was 91 (range 15-209). Six
      patients died from septic MODS. Ranson score, Acute Physiology and Chronic Health
      Evaluation (APACHE) II score during the first week of disease, pre-existing co
      morbidity, body mass index, infection and extent of necrosis were significantly
      associated with death (P < 0.01 for all parameters). However, only infection of
      the necrotic pancreas was an independent risk factor in the multivariate
      analysis. CONCLUSION: Early deaths in patients with severe acute pancreatitis are
      rare, mainly as a result of modern intensive care treatment. Nine of the ten
      deaths occurred more than 3 weeks after disease onset. Infection of pancreatic
      necrosis was the main risk factor for death.

PMID- 11442531
TI  - Resection rate and effect of postoperative chemotherapy on survival after surgery
      for colorectal liver metastases.
AB  - BACKGROUND: The purpose of this study was to investigate whether adjuvant therapy
      can improve survival after curative resection of colorectal liver metastases.
      METHODS: Some 235 patients had 256 liver resections for metastatic colorectal
      cancer. There were no predefined criteria for resectability with regard either to
      the number or size of the tumours or to locoregional invasion, except that
      resection had potentially to be complete and macroscopically curative. All
      patients who had curative hepatic resection were advised to start postoperative
      adjuvant chemotherapy. RESULTS: The resectability rate in screened patients was
      91 per cent (235 of 259 patients); the postoperative mortality rate was 4 per
      cent. In 35 patients resection of the primary tumour was performed simultaneously
      with partial liver resection. Forty-four patients (19 per cent) developed intra
      abdominal recurrence; 14 (6 per cent) underwent reoperation and the recurrent
      tumour was resected. Adjuvant chemotherapy was given to 99 patients (55 per
      cent), most treatments being based on 5-fluorouracil with folinic acid. The
      overall actuarial survival rates at 1, 3 and 5 years were 87, 60 and 36 per cent
      respectively. In a multivariate analysis, four or more metastases, preoperative
      carcinoembryonic antigen level higher than 5 ng/ml and a positive resection
      margin were independent predictors of poor outcome. Adjuvant chemotherapy
      improved the 5-year survival rate to 53 per cent. CONCLUSION: This study provides
      some evidence that postoperative chemotherapy is beneficial; however, prospective
      randomized studies are necessary to define its exact role.

PMID- 11442532
TI  - Gamma-glutamyl transpeptidase messenger RNA may serve as a diagnostic aid in
      hepatocellular carcinoma.

PMID- 11442533
TI  - Patterns of pelvic invasion are prognostic in the treatment of locally recurrent
      rectal cancer.
AB  - BACKGROUND: Local recurrence of rectal cancer after curative resection remains a
      difficult clinical problem. The aim of this study was to elucidate prognostic
      risk factors after resection of recurrent cancer. METHODS: Between January 1983
      and December 1999, 83 patients with locally recurrent rectal cancer were studied
      retrospectively for survival benefit by re-resection. Sixty patients underwent
      resection for recurrent cancer, including total pelvic exenteration in 30
      patients and sacrectomy in 23 patients. The extent of locally recurrent tumour
      was classified by the pattern of pelvic invasion as follows: localized, sacral
      invasion and lateral invasion. RESULTS: Multivariate analysis showed that the
      pattern of pelvic invasion was a significant prognostic factor which
      independently influenced survival after resection of recurrent cancer (P <
      0.001). The 5-year survival rates were 38 per cent in the localized type (n =
      27), 10 per cent in the sacral invasive type (n = 16) and zero in the lateral
      invasive type (n = 17). CONCLUSION: Resection for locally recurrent rectal cancer
      is potentially curative in patients with localized or sacral invasive patterns of
      recurrence. Alternatives should be explored in patients with recurrence involving
      the lateral pelvic wall.

PMID- 11442534
TI  - Criteria for extramural perineural invasion as a prognostic factor in rectal
      cancer.
AB  - BACKGROUND: An abundant extramural autonomic nerve network is an anatomical
      feature of the rectum. Extramural perineural invasion (PNI) may influence the
      prognosis after resection of rectal cancer, however, few assessment criteria
      exist. METHODS: PNI was investigated in 364 patients who underwent curative
      surgery for rectal cancer penetrating the muscular layer. A grading system was
      established based on the 'intensity' (number of PNI foci in a 20-power field) and
      'depth' (distance from the muscularis propria) of PNI. PNI-0 was defined as
      without PNI, PNI-1 as 'intensity' of less than five foci and 'depth' less than 10
      mm, and PNI-2 as five or more foci or 10 mm or greater 'depth' of invasion.
      RESULTS: PNI was observed in 52 patients (14 per cent) and strongly correlated
      with pathological tumour node metastasis (pTNM) stage. Five-year survival was
      related to PNI grade (74 per cent in PNI-0, 50 per cent in PNI-1 and 22 per cent
      in PNI-2). The rate of local recurrence was also related to PNI stage: 43 per
      cent in PNI-2 and 9 per cent in both PNI-0 and PNI-1. Multivariate analyses
      showed that graded PNI was associated both with local recurrence and long-term
      survival, independent of tumour depth (pTNM T) and nodal involvement (pTNM N).
      CONCLUSION: The PNI grading system may be useful in prognosis and allow case
      selection for intensive postoperative adjuvant therapy.

PMID- 11442535
TI  - Randomized study of coagulation and fibrinolysis during and after gasless and
      conventional laparoscopic cholecystectomy.
AB  - BACKGROUND: Carbon dioxide pneumoperitoneum may be an important
      pathophysiological factor stimulating the coagulation system during conventional
      laparoscopic cholecystectomy. The aim of this study was to test the hypothesis
      that gasless laparoscopy produces smaller changes in the coagulation and
      fibrinolytic system than carbon dioxide pneumoperitoneum in patients undergoing
      laparoscopic cholecystectomy. METHODS: Fifty patients were allocated randomly to
      conventional (n = 26) or gasless (n = 24) laparoscopic cholecystectomy. Blood
      samples were obtained on admission, after induction of anaesthesia, after
      insufflation or traction, 30 min after introduction of the laparoscope, 10 min
      after exsufflation of carbon dioxide or traction, 4 h after extubation and 24 h
      after operation. RESULTS: The two groups were comparable with respect to age,
      sex, body mass index and duration of operation. Plasma levels of prothrombin
      fragment 1 and 2 (F1 + 2), soluble fibrin and D-dimer did not differ between the
      two groups. F1 + 2 levels varied significantly in both groups during and after
      operation (P < 0.001). Soluble fibrin and D-dimer levels did not change during
      operation in either group, but after operation the levels increased significantly
      in both groups (P < 0.001). CONCLUSION: Carbon dioxide pneumoperitoneum does not
      enhance the activation of coagulation and fibrinolysis associated with
      laparoscopic cholecystectomy. The coagulation and fibrinolytic systems are
      activated during and after gasless as well as conventional laparoscopic
      cholecystectomy.

PMID- 11442536
TI  - Outcome and resource utilization in gastroenterological surgery.
AB  - BACKGROUND: A small minority of patients undergoing gastroenterological surgery
      are at high risk for postoperative complications, which may lead to prolonged
      hospital stay, disproportionate use of resources and increased mortality. The
      nature and frequency of, and predictive factors for, postoperative complications
      were studied and the impact of complications on resource utilization was
      assessed. METHODS: A prospective observational study was undertaken of 503
      patients undergoing gastroenterological surgery in a tertiary care centre. The
      incidence of cardiorespiratory, infective and surgical complications was
      assessed. The need for reoperation, intensive care and length of hospital stay,
      readmission, death at 6 months and costs were evaluated. RESULTS: Some 235
      patients (47 per cent) had at least one complication, most commonly delayed oral
      intake (n = 70). Complications were associated with cardiovascular disease,
      prolonged operation, high Physiological and Operative Severity Score for the
      enUmeration of Mortality and morbidity, and increased number of Shoemaker's
      criteria. The length of hospital stay of patients with complications was longer
      than that of those without complications (11 versus 6 days). Morbidity resulted
      in a twofold increase in median costs. CONCLUSION: High-risk patients could be
      identified by simple clinical criteria, although the commonly used risk criteria
      were not very sensitive. A reduction in postoperative complication rates would
      result in marked cost savings.

PMID- 11442537
TI  - The Seldinger technique for difficult transurethral catheterization: a gentle
      alternative to suprapubic puncture (Br J Surg 2000; 87: 1729-30).

PMID- 11442538
TI  - The Seldinger technique for difficult transurethral catheterization: a gentle
      alternative to suprapubic puncture (Br J Surg 2000; 87: 1729-30).

PMID- 11442540
TI  - Gender differences in the longitudinal pressure profile of the anal canal related
      to anatomical structure as demon strated on three-dimensional anal endosonography
      (Br J Surg 2000; 87: 1674-9).

PMID- 11442542
TI  - Rectal adenocarcinoma with liver metastases: management of the primary tumour (Br
      J Surg 2001; 88: 163-4).

PMID- 11442543
TI  - Epidemiology of abdominal aortic aneurysms in the Asian community (Br J Surg
      2001; 88: 382-4).

PMID- 11442544
TI  - Randomized trial of needlescopic versus laparoscopic cholecystectomy (Br J Surg
      2001; 88: 45-7).

PMID- 11442545
TI  - Randomized trial of needlescopic versus laparoscopic cholecystectomy (Br J Surg
      2001; 88: 45-7).

PMID- 11442547
TI  - The National Institute for Clinical Excellence and hernia repair.

PMID- 11442548
TI  - Probiotics (Br J Surg 2001; 88: 161-2).

PMID- 11442549
TI  - Low-dose aspirin for migraine prophylaxis in women.

PMID- 11442550
TI  - Headache in the HIV patient: a review with special attention to the role of
      imaging.
AB  - Headache is one of the most commonly encountered neurologically related
      complaints in HIV patients. The authors review the relationship between HIV
      infection and headache and discuss the role of neuroimaging in this select
      patient group.

PMID- 11442551
TI  - Low-dose aspirin for migraine prophylaxis in women.
AB  - Although migraine is more common among women than men, the only two large,
      randomized trials of low-dose aspirin for migraine prophylaxis have been
      conducted in men. As part of the Women's Health Study, an ongoing randomized
      trial of low-dose aspirin and vitamin E among 39 876 female health professionals
      aged 45 and older, 1001 women with frequent migraine attacks were assigned to 100
      mg of aspirin every other day (n = 525) or aspirin placebo (n = 476). Migraine
      frequency, as well as severity, duration, and degree of incapacitation, were
      assessed by self-report on questionnaires 12 months and 36 months after
      randomization, and also by monthly diaries kept before and after randomization.
      Women assigned to aspirin reported small and consistent decreases in migraine
      frequency (59.6% vs. 56.4% assigned to placebo reporting improvement at 36
      months; odds ratio 1.13, 95% confidence interval, 0.86--1.48), as well as
      decreases in severity, duration, and migraine-related incapacitation. These
      reductions were not, however, statistically significant. These data are
      compatible with a small treatment effect of low-dose aspirin in the prophylaxis
      of migraine among middle-aged women.

PMID- 11442552
TI  - Influence of intense light stimulation on trigeminal and cervical pain perception
      thresholds.
AB  - Thirty-three migraineurs and 23 healthy controls were submitted to pressure
      algometry before and after light-induced discomfort was elicited by progressive
      light stimulation in a monoblind fashion. Pressure algometries were performed on
      the emergence of the supraorbital, infraorbital, mental and greater occipital
      nerves, and over the temporal muscles, always throughout the same sequence and
      from right to left. Measurements were carried out before and immediately after
      light stimulation and after 10 min of the second algometry. The final result for
      each site measured at each time-point was the mean of the three measurements.
      Light stimulation was carried out progressively until light-induced discomfort
      was reported, to a maximum of 20,000 lux. A heat-blocking glass protected
      patients' eyes. Migraineurs presented significant and persistent drops in pain
      perception thresholds after light stimulation, at all sites tested (P = 0.002 to
      < 0.0001). These drops were not seen in controls, in whom, conversely, a less
      significant increase was seen on right infraorbital and left temporal muscle
      sites. Our results indicate that in migraineurs, light may have a relevant role
      in trigeminal and cervical pain perception thresholds.

PMID- 11442553
TI  - Pain thresholds and tenderness in neck and head following acute whiplash injury:
      a prospective study.
AB  - OBJECTIVE OF THE INVESTIGATION: In a 6-month prospective study of 141 consecutive
      acute whiplash-injured participants, and 40 acute, ankle-injured controls, pain
      and tenderness in the neck/head, and at a distant control site, were measured.
      BASIC PROCEDURES: Muscle palpation and pressure algometry in five head/neck
      muscle-pairs were performed after 1 week and 1, 3 and 6 months after injury.
      Algometry was performed at a distant control site. MAIN FINDINGS: Whiplash
      injured patients had lowered pressure-pain-detection thresholds and higher
      palpation-score initially in the neck/head, but the groups were similar after 6
      months, and the control site was not sensitized. PRINCIPAL CONCLUSION: Focal, but
      not generalized, sensitization to musculoskeletal structure is present until 3
      months, but not 6 months, after whiplash injury, and probably does not play a
      major role in the development of late whiplash syndrome. Pressure algometry and
      palpation are useful clinical tools in the evaluation of neck and jaw pain in
      acute whiplash injury.

PMID- 11442554
TI  - New-onset cluster headache in middle-age and elderly women.
AB  - Cluster headache is usually considered to affect young men. We hereby report on
      new-onset cluster headache in middle-aged and elderly women. We performed a
      retrospective chart review of female patients diagnosed with cluster headache
      (IHS criteria), and studied the charts of women in whom the headache started
      after the age of 50 years. Out of 168 patients (26 women, 15%) diagnosed with
      cluster headache, the headache started after the age of 50 years in seven women,
      of whom three reported past tension-type or migraine headaches. The mean age at
      the beginning of the headache was 61 +/- 8 years (range 52--72 years). In all
      cases, the pain was severe, strictly unilateral, and accompanied by at least one
      autonomic symptom. The average duration of the pain was 70 min (range 20 min--3
      h), recurring daily for an average period of 7 weeks (range 1--16 weeks). Five
      patients had 1--2 pain attacks each day, while the other two experienced up to
      eight episodes of pain in 1 day. In two patients the periodicity of the pain was
      currently undetermined. In the remainder, the headache periods recurred every 1-
      4 years. Cluster headache is commonly considered to be a young-male disorder, but
      middle-aged and elderly women may also be affected. The characteristics of the
      pain and its manner of occurrence were similar in our cases to those reported in
      the young-male population.

PMID- 11442555
TI  - Quality of life in adolescents with chronic pain in the head or at other
      locations.
AB  - The differences in quality of life and school absence were studied in one hundred
      adolescents from the open population who had reported chronic headache or
      chronic, physically unexplained, pain at other locations. The adolescents kept a
      3-week diary about their pain and completed a quality of life questionnaire. Of
      all chronic pain sufferers in this study, it was the adolescents with headache
      who showed the least frequent pain, but they reported the poorest quality of life
      and the largest school absence due to their pain. Adolescents with headache or
      adolescents with back pain showed the highest negative correlations between pain
      parameters and quality of life. Headache sufferers showed highly negative
      relationships between pain parameters and most quality of life domains (median r
      = -0.46), and only in headache sufferers did this involve both intensity and
      frequency of pain. Qualitative studies are needed to reveal the background to
      these differences.

PMID- 11442556
TI  - The Vaga study; epidemiology of headache I: the prevalence of ultrashort
      paroxysms.
AB  - In a large-scale study of headache epidemiology in Vaga, Norway, 1838 adult
      parishioners(18--65 years of age) were examined, and this represents 88.6% of the
      target group. Jabs and jolts syndrome/idiopathic stabbing headache (ISH) was
      verified in 35.2% of the questioned parishioners. This prevalence is much higher
      than previously observed ones. There were clearly more females than males, the
      female/male ratio being 1.49, as compared to a ratio of 1.06 in the study cohort
      (P-value: < 0.0001, chi(2) test). The ratio, 1.49, also differs clearly from a
      previously observed one: 6.6 (P-value = 0.0003, Fisher's exact test). Control
      studies included blinded re-check of 100 work-ups, with complete concurrence
      (kappa-value of 1.00 and blinded re-check of 41 individuals (kapp value of
      0.841). Jabs and jolts/ISH are frequent and almost the sole shortlasting
      (generally < 3 s duration) cephalic paroxysms.

PMID- 11442557
TI  - Supraorbital neuralgia: a clinical study.
AB  - A series of 18 patients suffering from supraorbital neuralgia have been studied
      through a seven year period. Appropriate investigations ruled out other
      headaches. There was a female (67%) preponderance. Mean age at onset was 51.6
      years. The mean headache duration was 5.9 years. Five patients had a history of
      ipsilateral forehead trauma. The main areas of pain were the forehead and orbit.
      The pain was dull with short sharp or burning exacerbations. The temporal pattern
      was either remitting (n = 7) or chronic continuous (n = 11). Autonomic
      accompaniments were generally lacking. Neurological assessment was normal in all
      but 4 patients who were found to have signs/symptoms of sensory dysfunction in
      the forehead of the symptomatic side. Trials of different drugs, including
      migraine and anti-neuralgic drugs, only provided slight relief. Anaesthetic nerve
      blocks of the supraorbital nerve provided an absolute but transitory relief of
      pain. Although aetiology and pathogenesis of supraorbital neuralgia is largely
      unknown, entrapment of the supraorbital nerve at its outlet and successful
      decompressive surgery have been previously reported. This and other pathogenic
      hypotheses are discussed.

PMID- 11442558
TI  - Quantitative EEG responses to ischaemic arm stress in migraine.
AB  - Several studies suggest that patients with migraine respond physiologically to
      stress differently from controls, yet experimental data are scarce. In order to
      evaluate the reactivity to stress in migraine, we recorded the quantitative
      electroencephalogram (qEEG) during non-noxious and noxious ischaemic arm stress
      in two groups of healthy controls and compared the results with the effects of
      non-noxious ischaemic arm stress in a group of patients with migraine. In the
      controls, non-noxious mild stress did not produce any qEEG change but noxious
      stress induced a significant decrease of the alpha power. By contrast, in
      migraine patients the non-noxious mild stress was sufficient to induce a
      significant decrease of the alpha power in all brain regions. The results of our
      study show that migraine sufferers display a lower threshold to physical stress
      and confirm previous studies indicating that migraine is a disease characterized
      by a state of altered neuronal excitability.

PMID- 11442559
TI  - Headache caused by drinking cold water is common and related to active migraine.
AB  - The primary aim of this study was to estimate the prevalence of cold-induced
      headache and to test if it is associated with migraine. Women attending a
      population-based mammography screening programme were asked to participate in the
      study. Fifty-one of 669 women (7.6%) experienced a headache after ingesting 150
      ml of ice-cold water through a straw. Women who had experienced one or more
      migraine attacks in the last year (active migraine) were twice as likely to
      experience a headache from ingesting the cold water as women who had never
      suffered from migraine. Ninety-five women who had experienced their most recent
      migraine attack more than 1 year ago (inactive migraine) were not at increased
      risk. The prevalence of active and inactive migraine was 19.4 and 14.2%,
      respectively. Headache caused by drinking cold water is common in women. The
      results indicate that active migraine facilitates the perception of forehead pain
      induced by a cold palatal stimulus.

PMID- 11442560
TI  - Short-lasting unilateral neuralgiform headache with conjunctival injection and
      tearing (SUNCT) following presumed dorsolateral brainstem infarction.

PMID- 11442561
TI  - Haemophilus influenzae: from the post-vaccination era to antibiotic resistance.

PMID- 11442562
TI  - HIV-associated visceral leishmaniasis.

PMID- 11442563
TI  - Recent developments in staphylococcal scalded skin syndrome.
AB  - Staphylococcal scalded skin syndrome describes a spectrum of superficial
      blistering skin disorders caused by the exfoliative toxins of Staphylococcus
      aureus. In its severe form, the exfoliation can spread to cover the entire body
      surface area. Two S. aureus exfoliative toxin serotypes affecting humans have
      been identified, but their purpose and mechanism of action have remained elusive.
      Based on their interaction with human and mouse epidermis, their three
      dimensional structure and site-directed mutagenesis studies, it is speculated
      that they act as atypical serine proteases, and desmoglein-1 has now been
      identified as the specific epidermal substrate. Recent studies also suggest that
      the toxins may have a unique superantigenic activity. Clinically, new rapid
      diagnostic tests have been developed, including one that is able to detect the
      toxins directly from serum. With early diagnosis and appropriate management,
      mortality in children remains low and long-term complications are rare because
      the lesions are superficial and heal rapidly without scarring. In adults,
      however, the condition carries a mortality of almost 60% despite aggressive
      treatment, usually because of serious underlying illness. The recent developments
      in our understanding of the exfoliative toxins should lead to new and improved
      diagnostic and therapeutic strategies, including the use of specific antixoxins
      to prevent exfoliation.

PMID- 11442564
TI  - Resistance to antibiotics and biocides among non-fermenting Gram-negative
      bacteria.
AB  - OBJECTIVE: To investigate the antibiotic and biocide susceptibilities of clinical
      isolates of rarely encountered Gram-negative, non-fermenting bacteria. METHODS:
      Thirty Gram-negative non-fermenting bacterial strains were isolated from blood
      cultures of oncology patients. These were studied for their resistance to 11
      antibiotics. Their susceptibilities to seven biocides used in hospitals were also
      examined. RESULTS: Isolates of Stenotrophomonas maltophilia and Ochrobactrum
      anthropi were generally resistant to at least five of the antibiotics, whereas
      isolates of Comamonas acidivorans, Flavobacterium oryzihabitans, Aeromonas
      hydrophila, Sphingobacterium spiritivorum, Acinetobacter junii and Acinetobacter
      lwoffi were generally sensitive to at least nine of the antibiotics.
      Trovafloxacin and trimethoprim-sulfamethoxazole were the most effective
      antibacterial agents tested, with 0% and 7%, respectively, of isolates being
      resistant, whereas 63% of isolates were resistant to aztreonam. Some isolates,
      sensitive to meropenem and/or ceftazidime in vitro, possessed very high MBC/MIC
      ratios for these beta-lactams. Two out of three biocides used in hospital
      pharmacies showed lethal activity towards all strains tested when used at less
      than one-third of their recommended in-use concentration. Proceine 40 failed to
      give a 5 log reduction in bacterial cell number for the isolates tested when used
      at its "in-use" concentration. A concentration of > 500 mg/L chlorhexidine was
      required to achieve a 5 log reduction for the same isolates. CONCLUSIONS: We have
      examined the antibiotic susceptibilities of non-fermenting Gram-negative
      bacterial strains isolated from immunocompromised patients. Despite being
      sensitive to certain antibiotics in vitro, some isolates were still able to cause
      serious bacteremia. We have also reported for the first time the susceptibilities
      of non-fermenting Gram-negative bacteria to common biocides used in hospital
      infection control, and have shown that some strains are able to persist at the
      "in-use" concentration of particular biocides. It is therefore important to study
      further this particular group of organisms, and, in particular, to examine
      whether there exists a link between resistance to antibiotics and resistance to
      biocides.

PMID- 11442565
TI  - Surveillance of antimicrobial resistance--what, how and whither?
AB  - OBJECTIVE: To express the views of a working party held to consider antibiotic
      resistance surveillance systems, their strengths and weaknesses, and their
      current and future applications. METHODS: The participants, all of whom were
      experienced in this field, discussed the development of surveillance systems in
      relation to the increasing prevalence of resistance to antibacterial agents and
      the current interest in surveillance systems shown by many official bodies, in
      both the human and veterinary fields. The problems inherent in surveillance
      systems were considered together with the applications of different systems.
      RESULTS: The properties of good antibiotic resistance surveillance systems were
      defined. Surveillance systems vary widely from those with a narrow base, focusing
      on few organisms in one disease area, to those covering many diseases, many
      organisms (including normal flora) and many compounds. Whatever their design,
      they should be able to detect significant differences and shifts in
      susceptibility to various antibacterial agents, and the information derived from
      them should reach as many interested parties as possible in a timely manner. In
      using this information to decide strategies, criteria for action need to be
      determined by pragmatic consensus. Funding remains a major problem, with few
      large studies being supported by official bodies in spite of their professed
      enthusiasm for surveillance. In consequence, many current systems are funded by
      the pharmaceutical industry and are of necessity restricted in their focus.
      CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well
      planned and well executed. Many current systems suffer from well-recognized but
      uncorrected biases. Consortium funding will be necessary for large schemes to be
      successful. There is no "ideal" surveillance system.

PMID- 11442566
TI  - Interpretive criteria of ceftibuten disk diffusion susceptibility tests according
      to the DIN 58 940 method.
AB  - OBJECTIVE: This study aimed to establish interpretive criteria for agar diffusion
      tests with ceftibuten disks according to DIN standards. METHODS: Minimal
      inhibitory concentrations (MICs) and inhibition zones produced by ceftibuten in
      the disk diffusion test were determined for 275 recent bacterial isolates,
      including 11 species with 25 strains each. Regression analysis was performed for
      two disk loads (10 microg and 30 microg). RESULTS: Correlation of MICs and zone
      diameters was good, with correlation coefficients of r = - 0.97 for both tested
      disk loads. Evaluation of the calculated zone size criteria for all species
      showed no very major discrepancies or no major discrepancies. The 30-microg
      disks, however, produced unacceptably large inhibition zones for very susceptible
      strains, so that usage of 10-microg disks must be recommended when testing
      according to DIN standards. CONCLUSION: Based on the MIC breakpoints recommended
      by the DIN (> or =8 mg/L and < or = 1 mg/L), the following interpretive
      breakpoints for disk diffusion susceptibility tests with 10-microg ceftibuten
      disks were calculated using regression line analysis: < or =19 mm for resistance
      and > or = 27 mm for susceptiblity. Proposed inhibition zone diameters for the
      reference strain Escherichia coli ATCC 25922 are between 31 and 36 mm.

PMID- 11442567
TI  - Comparative evaluation of three commercial software packages for analysis of DNA
      polymorphism patterns.
AB  - OBJECTIVE: In the present study we have compared three commercial software
      packages, GelCompar, Molecular Analyst Fingerprinting, and BioImage, to determine
      if the results generated by the programs were comparable and correlated
      adequately with visual interpretation of electrophoretic gels, in the analysis of
      several well characterized incidents of infections. METHODS: Infections caused by
      Pseudomonas aeruginosa, Candida dubliniensis, C. albicans, and serotypes of
      Salmonella were characterized by restriction endonuclease analysis,
      macrorestriction analysis of genomic DNA with pulsed-field gel electrophoresis,
      and random amplified polymorphic DNA. The genotypes were visually detected based
      on band presence or absence in the different gels. The similarity values of DNA
      profiles were computed using Dice coefficient and were presented in dendrograms
      by UPGMA. The concordance or agreement between the number of genotypes obtained
      and their clustering, using the computerized programs, was determined. RESULTS:
      In general, agreement in number of genotypes obtained visually and by using the
      commercial DNA analysis software was achieved, but discrepancies were also
      denoted between the systems. The concordance between the visual and the
      computerized analysis ranged from 72% to 100%. CONCLUSION: In our experience,
      although the programs evaluated in the present study performed acceptably well,
      such programs may be used as an aid in the analysis of complex banding patterns,
      and they do not provide an indisputably correct analysis in genotype definition.

PMID- 11442568
TI  - Diagnosis at first glance: septic shock in a patient with multiple episodes of
      fever, abdominal pain and leg inflammation.

PMID- 11442569
TI  - Susceptibility of pneumococci to evernimicin: effect of CO2 and different
      methodologies.

PMID- 11442570
TI  - Antimicrobial susceptibilities and ESBL production rates of Salmonella and
      Shigella strains in Turkey.

PMID- 11442573
TI  - Effects of a high-fat meal on resistance vessel reactivity and on indicators of
      oxidative stress in healthy volunteers.
AB  - High fat meals postprandially impair macrovascular endothelial function and a
      link to increased oxidative stress is suggested. Few information, on the other
      hand, exists on the effect of postprandial hyperlipidaemia on resistance vessel
      function. Under normal circumstances this vascular bed regulates tissue perfusion
      and, by controlling flow, impacts on macrovascular nitric oxide formation. The
      impact of a high fat meal (1200 kcal, 90 g fat, 46 g protein and 47 g
      carbohydrates) on postprandial resistance vessel reactivity and on indicators of
      oxidative stress was studied in 11 healthy subjects by venous-occlusion
      plethysmography using another six subjects as time control group. Ingestion of
      the test meal resulted in a pronounced increase of serum triglycerides from 1.05
      +/- 0.61 mmol l(-1) in the fasting state to peak postprandial values of 1.94 +/-
      0.41 mmol l(-1) (P < 0.001) reached after 4 h and a return to baseline after 8 h.
      Fasting peak reactive hyperaemia (RH) was 19.6 +/- 2.4 ml min(-1) (100 ml)(-1).
      Two hours after ingestion of the test meal peak RH was transiently reduced to
      16.8 +/- 2.2 ml min(-1) (100 ml)(-1) (P < 0.05). No alteration of resting forearm
      perfusion was observed. The time course of peak RH suggested a potential biphasic
      effect of the test meal with an early impairment and a late increase of RH.
      Ingestion of a lipid rich test meal did not exert any influence on either total
      plasma antioxidant capacity given in trolox equivalents (513 +/- 26 micromol l(
      1) at baseline) or on plasma peroxides measured as H2O2 equivalents (469 +/- 117
      micromol l(-1)). Our results suggest that ingestion of a meal containing 90 g of
      fat results in a transient impairment of reactive hyperaemia in healthy subjects
      but these vascular alterations are not accompanied by signs of systemically
      increased oxidative stress.

PMID- 11442574
TI  - Heart rate dynamics and cardiorespiratory coordination in diabetic and breast
      cancer patients.
AB  - Objective of this study was to evaluate cardiac autonomic function in female
      breast cancer patients on the basis of linear and non-linear heart rate
      variability (HRV) as well as on musical heart rate rhythmicity. The latter method
      has been recently developed and enables particularly the quantification of
      cardiorespiratory coordination solely on the basis of ECG recordings. To provide
      a broad basis of comparability, 37 breast cancer patients were compared with 37
      age-matched healthy women and 40 age-matched female diabetic patients who serve
      as pathological controls. During night sleep, all parameters showed a tendency
      towards lower variability, complexity or rhythmicity of HRV in cancer patients.
      The most prominent alterations were found for the binary pattern predominance
      (PP) and for the ratio of heart rate and respiration. In particular, when
      comparing metastasized and non-metastasized cancer patients, the discriminatory
      power of binary heart rate rhythmicity emerges: the histograms of 1-h intervals
      during night sleep with a predominance of cyclically recurrent phase locking
      patterns unveiled a clear transition from higher to lower cardiorespiratory
      coordination ratios and to a loss of coordination capability in metastasized
      patients.

PMID- 11442575
TI  - Alveolar albumin leakage during large tidal volume ventilation and surfactant
      dysfunction.
AB  - Detergent given as an aerosol and large tidal volume ventilation (LTVV) have been
      observed, by us, to promote lung injury by an additive effect on alveolocapillary
      barrier function. The surfactant system may be further damaged if protein leakage
      occurs into the alveoli. The aim was to study the effect of detergent and LTVV on
      the alveolar leakage of albumin and also the effect of detergent on surface
      activity of lung washings and lung tissue extracts. Technetium-99m-labelled human
      serum albumin was given intravenously. The alveolar leakage of albumin was
      measured after perturbing the surfactant system with the detergent dioctyl sodium
      sulfosuccinate either singly or in combination with LTVV. Four groups of rabbits
      were studied after 3 h of experimental ventilation. Surface tension measurements
      of tissue extracts, lung mechanics and gas exchange did not show any differences
      between groups. Wet lung weight and albumin leakage were significantly increased
      in the two groups subjected to LTVV compared with groups given normal tidal
      volume ventilation. Low doses of detergent did not affect surface activity of
      lung tissue extracts or alveolar leakage of albumin. LTVV increased alveolar
      leakage of albumin and produced oedema. No additive effect was seen when
      detergent and LTVV were combined.

PMID- 11442576
TI  - Spectral analysis of heart rate variability and respiration during sleep in
      cocaine-exposed neonates.
AB  - This study's objective was to examine the autonomic control of heart rate and
      respiration during the neonatal period in human infants with prenatal exposure to
      cocaine. Four-hour daytime recordings of the electrocardiogram (ECG) were
      obtained from 15 cocaine-exposed and 13 non-exposed full-term neonates at 2 weeks
      of age during quiet sleep (QS) and active sleep (AS). For each 1-min epoch of
      sleep, the power spectrum of the R-R intervals was computed from the ECG to
      obtain the total power (0-2 Hz), and spectral power in the high-frequency (HFP,
      0.3-2 Hz), mid-frequency (MFP, 0.1-0.2 Hz), and low-frequency (LFP, 0.03-0.1 Hz)
      bands. Respiration was also monitored and processed using similar spectral
      analysis procedures. Cocaine-exposed neonates showed enhanced heart rate
      variability reflected by an increase in spectral power across all frequency
      bands. Spectral power in LFP and MFP was higher in cocaine-exposed neonates
      during both sleep states, but only in HFP during QS. There were no respiratory
      patterning differences between the groups to account for these findings. The
      index of sympathovagal balance (LFP + MFP)/HFP, showed no differences between the
      groups. We conclude that infants exposed to cocaine in utero show differences in
      the modulation of heart rate reflecting an increase in both vagal and sympathetic
      influences.

PMID- 11442577
TI  - The mode of left ventricular pumping: is there an outer contour change in
      addition to the atrioventricular plane displacement?
AB  - The outer contour of the heart has in some studies been shown to be constant
      during the heart cycle and the epicardial apex almost stationary whilst the base
      of the ventricles moves towards apex during systole. The base of the left
      ventricle has been regarded as a cylinder with constant cross-sectional area with
      changes in height during the heart cycle, the latter corresponding to the
      amplitude of mitral annulus motion (MAM). In this echocardiographic study,
      including 20 healthy adults, the stroke volume calculated by the cylinder model
      was significantly lower than by a reference method (modified Simpson's rule). MAM
      explained 82% of the stroke volume and 18% must, therefore, be explained by an
      inward motion of the outer left ventricular wall. A mean outer diameter
      shortening of about 3% (about 2 mm) was calculated.

PMID- 11442578
TI  - An integrated model of the human ventilatory control system: the response to
      hypercapnia.
AB  - This work presents a mathematical model of the human respiratory control system,
      based on physiological knowledge. It includes three compartments for gas storage
      and exchange (lungs, brain tissue and other body tissues), and various kinds of
      feedback mechanisms. These comprehend peripheral chemoreceptors in the carotid
      body, central chemoreceptors in the medulla and a central ventilatory depression.
      The latter acts by reducing the response of the central neural system to the
      afferent peripheral chemoreceptor activity during prolonged hypoxia of the brain
      tissue. Furthermore, the model considers local blood flow adjustments in response
      to O2 and CO2 arterial pressure changes. In this study, the model has been
      validated by simulating the response to square changes in alveolar PCO2,
      performed at different constant levels of alveolar PO2. A good agreement with
      data reported in the literature has been checked. Subsequently, a sensitivity
      analysis on the role of the main feedback mechanisms on ventilation response to
      CO2 has been performed. The results suggest that the ventilatory response to CO2
      challenges during hyperoxia can be almost completely ascribed to the central
      chemoreflex, while, during normoxia, the peripheral chemoreceptors provide a
      modest contribution too. By contrast, the response to hypercapnic stimuli during
      hypoxia involves a complex superimposition among different factors with disparate
      dynamics. Hence, results suggest that the ventilatory response to hypercapnia
      during hypoxia is more complex than that provided by simple empirical models, and
      that discrimination between the central and peripheral components based on time
      constants may be misleading.

PMID- 11442579
TI  - An integrated model of the human ventilatory control system: the response to
      hypoxia.
AB  - The mathematical model of the respiratory control system described in a previous
      companion paper is used to analyse the ventilatory response to hypoxic stimuli.
      Simulation of long-lasting isocapnic hypoxia at normal alveolar PCO2 (40
      mmHg=5.33 kPa) shows the occurrence of a biphasic response, characterized by an
      initial peak and a subsequent hypoxic ventilatory decline (HVD). The latter is
      about as great as 2/3 of the initial peak and can be mainly ascribed to prolonged
      neural hypoxia. If isocapnic hypoxia is performed during hypercapnia (PACO2=48
      mmHg =6.4 kPa), the ventilatory response is stronger and HVD is minimal (about
      1/10-1/5 of the initial peak). During poikilocapnic hypoxia, ventilation exhibits
      smaller changes compared with the isocapnic case, with a rapid return toward
      baseline within a few minutes. Moreover, a significant undershoot occurs at the
      termination of the hypoxic period. This undershoot may lead to apnea and to a
      transient destabilization of the control system if the peripheral chemoreflex
      gain and time delay are twofold greater than basal.

PMID- 11442580
TI  - The effect of glutamine on protein balance and amino acid flux across arm and leg
      tissues in healthy volunteers.
AB  - BACKGROUND: Glutamine is important in nitrogen transportation and the
      physiological control of acid-base regulation. In addition, it has been assumed
      that glutamine regulates protein balance in skeletal muscles based on findings in
      both experimental and clinical studies. However, little information on glutamine
      and its effect on protein dynamics in normal individuals is available. Therefore,
      the aim of this study was to evaluate whether glutamine improves protein balance
      and uptake of various indispensable amino acids across peripheral tissue in
      healthy individuals. MATERIAL AND METHODS: Standard primed constant infusions of
      L-[ring-2H5]phenylalanine and [ring 3,3-2H2]tyrosine (2 micromol kg(-1) h(-1))
      were performed after overnight fast in five healthy male volunteers before and
      during infusions of a standard and a glutamine/tyrosine enriched amino acid
      solution. Flux measurements of amino acids (AA) including 3-methylhistidine,
      glucose, lactate and free fatty acids (FFA) were performed across arm and leg
      tissues. RESULTS: Infusion of the standard AA solution (0.2 g N kg(-1) day(-1))
      increased the net uptake of individual amino acids, but provision of the enriched
      solution (0.4 g N kg(-1) day(-1)) with increased amounts of glutamine and
      tyrosine seemed to compete unfavourably with the net uptake of other key amino
      acids as methionine and phenylalanine, which are indispensable in muscles for
      protein synthesis. Increased flux of amino acids across peripheral tissues did
      not influence on flux of glucose, free fatty acid and lactate. CONCLUSIONS:
      Glutamine provision did neither stimulate protein synthesis nor attenuate
      breakdown of either globular or myofibrillar proteins in skeletal muscles of
      healthy volunteers.

PMID- 11442581
TI  - Spirometric reference values in Estonian schoolchildren.
AB  - This study was conducted to describe the relationship between anthropometric
      parameters and lung function in Estonian children, to determine the reference
      values for spirometry, and to compare these results with other data sets. The
      results are based on 1170 healthy non-smoking children (643 girls and 527 boys),
      aged 6-18 years. The spiroanalyser Pneumoscreen II (Jaeger) was used to register
      dynamic lung parameters. Natural logarithmic values of lung volumes, standing or
      sitting height and age were used in the final regression model. Prediction
      equations for forced vital capacity (FVC), forced expiratory volume in 1 s
      (FEV1), peak expiratory flow, forced expiratory flows when 50 and 75% of FVC has
      been exhaled, and mean forced expiratory flow over the middle 50% of the FVC for
      both sexes are presented. In comparison with recent data from European children
      the reference values were close for FVC, the differences were bigger for FEV1 and
      forced expiratory flows, especially in taller children.

PMID- 11442582
TI  - Bone mineral density of visually handicapped women.
AB  - While physical activity is an essential factor for muscle performance and
      development and also for the maintenance of bone mass in the loaded bones,
      apparently low intensity of physical activity of blind persons may compromise the
      muscle performance and bone mineral density (BMD). Therefore, the aim was to
      study whether there are differences in BMD of the weight-bearing or non-weight
      bearing bones between visually handicapped persons and those with normal sight.
      Nineteen visually handicapped premenopausal women and their matched pairs were
      recruited to the study. The mean age of the visually handicapped women was 39.9
      years (SD 8.1) and that of the women with normal vision 39.7 years (6.5). BMD of
      the distal radius, femoral neck and trochanter was measured with dual energy X
      ray absorptiometry (DXA), and isometric muscle strength of the extremities and
      trunk with a dynamometer. Between-group differences were compared with paired
      Student's t-test. The BMD at the femur was 8% higher in favour of the group with
      normal sight, whereas radial BMD was similar in the two groups. The t-score was 
      1.0 (95% confidence interval -1.5 to -0.5) for the femoral neck BMD and -0.7 (
      1.1 to -0.2) for the trochanter BMD in the group with impaired vision. The
      respective t-scores for the group with normal sight were -0.3 (-0.9 to 0.3) for
      the femoral neck and 0 (-0.7 to 0.7) for the trochanter. Visual handicap seems to
      be a risk for lower BMD of the weight-bearing proximal femur, but not for lower
      BMD of the non-weight-bearing distal radius.

PMID- 11442583
TI  - Isoresistive dynamometer measurement of trunk muscle velocity at different
      angular phases of flexion and extension.
AB  - Isoresistive trunk muscle dynamometer is a potentially useful piece of equipment
      in evaluation of trunk muscle velocity, but to date, studies analysing the
      possibilities and limitations of such measurements are scarce. The aim of this
      study was to analyse the trunk muscle velocity in repetitive flexion and
      extension movements at three different angular phases, using an isoresistive
      trunk muscle dynamometer, and to assess the reliability of the measurements. The
      study population consisted of 120 healthy, sedentary men and women who
      volunteered for the study. The measurements were carried out before and after a
      22-week training intervention programme. The results show that the peak
      velocities of the phases between 15 and 35 degrees in flexion and 20-0 degrees in
      extension (i.e. the second phases) correlated highly (r=0.99 in flexion and in
      extension) with the peak velocity of the whole movement ranging from -5 to 55
      degrees in flexion and 40 to -20 degrees in extension. Correlations were high,
      both before and after the intervention. The LISREL model analysis showed high
      reliability of measurement for the second angular phases (in flexion and
      extension). According to the model, the correlation between the first and second
      measurement (with a 22-week training intervention in between) was 0.78 in flexion
      and 0.81 in extension. In conclusion, the angular phases from 15 to 35 degrees in
      flexion and from 20 to 0 degrees in extension represent the peak velocity of the
      whole movement. Negative residual correlations between the first and last angular
      phases in the LISREL model reflect the way of performing the movement: the faster
      the start the slower the end, and vice versa.

PMID- 11442584
TI  - Evidence-based medicine for dermatologic surgeons: concepts in critical appraisal
      of information.
AB  - BACKGROUND: The term evidence-based medicine (EBM) is increasingly being used.
      Physicians, journal editors, insurance companies, and patients are applying its
      tenets to clinical decision making. Although there are concerns about the overly
      zealous application of EBM to clinical situations, many of the basic concepts are
      important in improving decision making. OBJECTIVE: To define evidence-based
      medicine and to review potential problems in basing decision making entirely on
      less-than-ideal evidence. METHODS: We reviewed the EBM literature and looked for
      examples in dermatology of pitfalls in decision making based on poor evidence.
      RESULTS: Following a definition of EBM, we review problems inherent in anecdotes
      and uncontrolled trials, including the placebo effect. Examples of medical
      practice that have been altered by doing more rigorous studies are provided.
      CONCLUSIONS: Concepts of EBM as currently defined should be considered by
      dermatologic surgeons in assessing the available information for clinical
      decision making.

PMID- 11442585
TI  - Laser resurfacing-induced hypopigmentation: histologic alterations and
      repigmentation with topical photochemotherapy.
AB  - BACKGROUND: Hypopigmentation is a relatively common side effect of CO2 laser
      resurfacing. Little is known regarding the histologic features of the areas of
      pigmentation loss. To date, hypopigmentation is considered a permanent
      complication of this procedure. OBJECTIVE: To assess the histologic features of
      hypopigmentation caused by laser resurfacing and to evaluate the efficacy and
      safety of topical psoralen photochemotherapy. METHODS: Ten patients were included
      in this pilot study. Four had baseline biopsies performed. Histologic parameters
      assessed included epidermal melanin, dermal melanophages, perivascular
      inflammation, Mel-5 immunostaining for melanocytes, and dermal fibrosis. Seven
      patients were treated twice a week with topical photochemotherapy utilizing
      0.001% 8-methoxypsoralen. RESULTS: All of the biopsy specimens demonstrated
      varying quantities of epidermal melanin and residual epidermal melanocytes. Mild
      perivascular inflammation was evident in two specimens. Superficial dermal
      fibrosis was noted in all biopsy specimens. Topical photochemotherapy induced
      moderate to excellent repigmentation in 71% of the treated patients. Adverse
      effects were minimal. CONCLUSION: The results of this investigation suggest that
      hypopigmentation induced by laser resurfacing may result from a suppression of
      melanogenesis rather than destruction of area melanocytes. The preliminary data
      further suggest that hypopigmentation caused by laser resurfacing can be
      effectively treated by topical photochemotherapy.

PMID- 11442586
TI  - Treatment of pyogenic granuloma with a sclerosing agent.
AB  - BACKGROUND: Pyogenic granulomas have been treated by cryosurgery, curettage,
      electrodesiccation, chemical cauterization, and laser surgery. The therapeutic
      effects of these conservative treatments are limited, however. OBJECTIVE: In this
      study, the efficacy of a sclerosing agent (monoethanolamine oleate) was evaluated
      for the treatment of pyogenic granuloma. METHODS: Pyogenic granuloma was treated
      by local injection of the monoethanolamine oleate solution in nine patients who
      were from 1 to 57 years of age (median 18 years). The treatment effect was
      determined by physical examination. RESULTS: All lesions were removed completely
      with no recurrence, and scars were inconspicuous in all cases. Complications
      occurred in only one patient who complained of pain due to an avoidable injection
      of excess solution. CONCLUSION: Sclerotherapy with monoethanolamine oleate is
      effective in the treatment of pyogenic granuloma and offers an alternative to
      conventional methods in cases for which conservative treatment is preferable.

PMID- 11442587
TI  - Microdermabrasion: a clinical and histopathologic study.
AB  - BACKGROUND: Microdermabrasion is a widely performed skin rejuvenation procedure.
      Few studies have examined its efficacy. OBJECTIVE: To evaluate the clinical and
      histopathologic effects of microdermabrasion. METHODS: Fourteen patients
      underwent microdermabrasion treatments over 12-14 weeks. Self-rated
      questionnaires were given before and after the treatment series and were
      evaluated by a paired t-test. Three of the 14 patients were treated for moderate
      to severe acne scarring. Acute histologic effects were assessed ex vivo on human
      abdominal skin. Chronic histopathologic effects were examined in three volunteers
      who underwent skin biopsies before and after a treatment series on the dorsal
      forearms. RESULTS: By patient assessment, there was statistically significant
      improvement in roughness, mottled pigmentation, and overall improvement of skin
      appearance, but not in rhytides. Acne scarring sometimes improved, but required
      deeper ablation. Acutely the stratum corneum was homogenized and focally
      compacted. Chronically there was epidermal hyperplasia, decreased melanization,
      and some increase in elastin. CONCLUSION: Microdermabrasion improves some aspects
      of photoaging and select cases of acne scarring.

PMID- 11442588
TI  - Perineural invasion of cutaneous malignancies.
AB  - BACKGROUND: Perineural invasion is an important mode of tumor spread and is
      associated with increased aggressiveness and a propensity for recurrence among
      cutaneous malignancies. OBJECTIVE: To review the pathogenesis, diagnosis, and
      treatment of cutaneous tumors exhibiting perineural invasion. METHODS: This
      article is based on a review of the medical literature concerning tumors with
      perineural involvement. RESULTS: This article describes the clinical signs and
      histologic features of cutaneous malignancies exhibiting perineural involvement.
      CONCLUSION: Appropriate patient care mandates consideration of perineural
      invasion in the evaluation of cutaneous tumors. As the majority of patients
      present without symptoms of neural involvement, physicians must be vigilant in
      the search for this type of tumor spread.

PMID- 11442589
TI  - Multi-injection plate for botulinum toxin application in the treatment of
      axillary hyperhidrosis.

PMID- 11442590
TI  - Cryostripping of the long saphenous vein with a percutaneously guided probe.
AB  - BACKGROUND: Although the technique of vein removal with a cryoprobe is both
      simple and well known, it has not yet been widely accepted. A modified probe now
      eliminates difficulties in its use. OBJECTIVE: The original probe has a tip that
      can be cooled with NO2 or CO2 to -85 degrees C to permit stripping by freezing
      the vein to the probe from inside the vein. This tip has now been provided with
      an anatomic curvature and a flexible guide tip, making it easier to introduce the
      probe into the incision and guide it distally with percutaneous support. WE
      report on the use of this modified instrument to strip 325 long saphenous veins.
      RESULTS: The modified probe has permitted us to increase the percentage of
      complete stripping procedures without further distal incisions from 67% to 91%.
      The procedure was successful in 62% of veins that had already undergone previous
      sclerosing procedures. Incomplete removal or duplicated long saphenous veins were
      easily remedied by subsequent stripping starting proximally from a small, distal
      incision. CONCLUSION: Stripping of the long saphenous vein with this modified and
      easily guided cryoprobe is rapid, uncomplicated, highly effective, and leaves
      fewer scars.

PMID- 11442591
TI  - Skin temperature measurements during intense pulsed light emission.
AB  - BACKGROUND: Although lasers and intense pulsed light sources have improved the
      capability of injuring veins without affecting the overlying skin, work is needed
      to improve the procedure. OBJECTIVE: To create a method for predicting skin
      reaction to pulsed light. METHODS: Twenty patients were divided into four groups
      according to skin type (I-IV). An industrial thermometer equipped with a laser
      aiming system was adapted to the intense pulsed light source handpiece. Patients
      received shots of increasing intensity while the skin temperature was measured.
      RESULTS: Fluence and temperature data were analyzed by logistic regression to
      evaluate possible injury. The stepwise method selected skin type and temperature
      variation as predictors of skin injury. Logistic curves indicated the maximum
      temperature variation tolerable for each skin type. More pigmented skin types
      tolerated less temperature increase. CONCLUSION: Skin type can predict cutaneous
      reaction to intense pulsed light through measurements of temperature variation.
      This method may help achieve successful selective photothermolysis.

PMID- 11442592
TI  - Current histologic preparation methods for Mohs micrographic surgery.
AB  - BACKGROUND: Recently Mohs micrographic surgery, which is widely used for the
      removal of nonmelanoma skin cancers, has been used to remove lentigo maligna with
      both rush permanent sections and frozen sections. Several investigators have
      incorporated the use of immunohistochemical techniques to aid in the
      interpretation of the specimens. OBJECTIVE: To determine the current practices of
      Mohs surgery laboratories, including the use of immunostains and automation of
      laboratory processes. METHODS: A total of 108 laboratories responded to a written
      questionnaire with 13 items about the types of tumors resected, routine stains
      performed, average number of slides processed per day, and use of automation and
      immunostains. RESULTS: Forty-nine percent of the laboratories are completely
      manual and 51% are automated. The Linistainer automated system, which is the
      predominant one used, decreased processing time by about 30% and provided an
      estimated 21-30% improved quality. Automation was associated with the number of
      slides processed. Immunostaining is performed by a limited number of laboratories
      which use the technique for basal and squamous cell carcinoma, lentigo maligna,
      and dermatofibrosarcoma protuberans. CONCLUSION: Automation of routine slide
      preparation with a Linistainer decreased staining variability by providing a
      consistent environment, and decreased processing time. Most laboratories do not
      perform immunostaining. The relatively high cost of reagents, lack of a reliable
      automated process, the additional time to process specimens, and the additional
      technician and physician time makes the procedure impractical for many
      laboratories.

PMID- 11442593
TI  - Squamous cell carcinoma in situ (Bowen's disease) in renal transplant patients
      treated with 5% imiquimod and 5% 5-fluorouracil therapy.
AB  - BACKGROUND: Depending upon the patient's age at transplant, skin type, sun
      exposure, and the need for immunosuppressive therapy to prevent rejection, there
      is escalation in the development of cutaneous malignancies in organ transplant
      patients a number of years after transplantation. Thus, with the expansion in
      these procedures over the past decades, and the ever-lengthening survival of
      these patients, we are seeing an increase in cutaneous malignancies in this
      patient population. OBJECTIVE: To determine if combined therapy with 5% 5
      fluorouracil and 5% imiquimod may be useful in the treatment of squamous cell
      carcinoma in situ. METHODS: We present five renal transplant patients, all more
      than 10 years posttransplantation, three with insulin-dependent diabetes, who
      developed multiple areas of squamous cell carcinoma (SCC) in situ. All these
      patients were on chronic immunosuppressive chemotherapy to prevent rejection, but
      were otherwise doing well. All the patients had biopsy-proven SCC in situ on
      their lower extremities that even in normal patients may be a challenge to treat.
      RESULTS: We treated these five patients with a combination of a local immune
      therapy, imiquimod cream, and a topical chemotherapeutic agent, 5% 5-fluorouracil
      (5-FU), with clearing of the areas of SCC in situ. CONCLUSION: Although
      immunotherapy must be used with caution in organ transplant patients to avoid
      graft rejection, topical imiquimod is a local immune modulator that potentiates
      local innate and possible adaptive immunity without measurable effects on
      systemic immunity. In addition, there is evidence that cytokines induced by
      imiquimod may improve the therapeutic efficacy of topical 5% 5-FU in the
      treatment of SCC in situ.

PMID- 11442594
TI  - Treatment of vitiligo with suction epidermal grafting by the use of an ultrapulse
      CO2 laser with a computerized pattern generator.
AB  - BACKGROUND: Laser ablation is used to remove the recipient epidermis in the
      suction epidermal grafting in vitiligo surgery. OBJECTIVE: To evaluate the
      effectiveness and safety of a suction epidermal grafting method after the removal
      of the epidermis by the use of the Ultrapulse CO2 laser with a computerized
      pattern generator. METHODS: Eleven patients with 34 lesions of refractory stable
      vitiligo were studied. RESULTS: Of the 34 lesion sites, excellent repigmentation
      was seen in 30 and the other 4 had good repigmentation. No complications
      occurred. CONCLUSION: The Ultrapulse CO2 laser is particularly well suited for
      deepithelialization in vitiligo surgery.

PMID- 11442595
TI  - Improved scalp surgery results by controlling tension vector forces in the
      tissues by galea to pericranium fixation sutures.
AB  - BACKGROUND: Tension, manifesting at the time of wound closure, limits the extent
      of tissue excision and predisposes to complications. Extensive undermining may be
      an unreliable technique to reduce tissue tension in surgery. Pericranium is a
      rarely used tissue in scalp surgery. OBJECTIVE: To show that the surgical
      technique of deep plane fixation reduces tissue tension at and adjacent to the
      wound, allowing relatively greater excision and reduced tension closure, and
      extensive undermining may be an ineffectual and potentially harmful surgical
      technique. I also update the surgical anatomy of the pericranium and determine
      its utility in scalp reconstructive surgery. METHODS: More than 1000 scalp
      operations, including 700 clinical investigative procedures, were done which
      included pericranial flaps, subgaleal and subperiosteal scalp reductions, and
      deep plane fixation. RESULTS: The alopecia removal operation described herein
      utilizing deep plane fixation is largely complication free and achieves tension
      reduced closure and between 18% and 50% greater tissue removal compared with
      conventional alopecia reduction procedures. CONCLUSION: Pericranium is a valuable
      and readily usable tissue in reconstructive scalp surgery.

PMID- 11442596
TI  - Distal digital keratoacanthoma: two cases with a review of the literature.
AB  - BACKGROUND: Distal digital keratoacanthoma (DKA) is an uncommon tumor difficult
      to diagnose clinically, and even histologically, with certainty. OBJECTIVE: Our
      purpose is to report on two new cases and to discuss the clinical, histologic,
      and differential diagnosis. METHODS: We have reviewed all well documented cases
      published in the literature. RESULTS: No single diagnostic criterion is
      sufficiently sensitive and specific to be pathognomonic. CONCLUSION: The
      diagnosis of DKA should be based on the correlation of clinical, radiological and
      pathologic findings, but the tumor is frequently diagnosed histologically as
      "squamous cell carcinoma, keratoacanthoma type" or as keratocarcinoma.

PMID- 11442597
TI  - Longitudinal melanonychia.
AB  - BACKGROUND: Ungual melanoma is the most serious disease affecting the nail. The
      majority start with a longitudinal brown streak in the nail. OBJECTIVE: To
      outline the different nail pigmentations, their differential diagnoses,
      treatment, and prognosis. METHOD: Clinical and histologic evaluation of dark nail
      pigmentations. CONCLUSION: Brown to black nail pigmentation may be due to
      different coloring substances of exogenous and endogenous origin. Exogenous
      pigmentations usually are not streaky or do not present as a stripe of even width
      with regular borders. Bacterial pigmentation, most commonly due to Pseudomonas
      aeruginosa or Proteus spp., have a greenish or grayish hue and the discoloration
      is often confined to the lateral edge of the nail. Subungual hematoma may result
      from a single heavy trauma or repeated microtrauma which often escapes notice.
      The latter is usually found on the medial aspect of the great toe. Although oval
      in shape, it commonly does not form a neat streak. Melanin pigmentation in the
      form of a longitudinal streak in the nail is due to a pigment-producing focus of
      melanocytes in the matrix. Neither the color intensity nor the age of the patient
      are proof of benignity or malignancy although subungual melanomas are very rare
      in children and malignant longitudinal melanonychia is usually wider than 5 mm.
      Hutchinson's melanotic whitlow, nail dystrophy, and a bleeding mass strongly
      suggest malignancy. Treatment is as conservative as possible in order to keep the
      tip of the digit; once the melanoma is completely removed, amputations have not
      been shown to prolong the disease-free survival time.

PMID- 11442598
TI  - Basal cell carcinoma arising from epidermoid cyst: a case report.
AB  - Cutaneous epidermoid cysts are very common lesions, but neoplastic transformation
      of their epithelium is extremely rare. We describe a patient with basal cell
      carcinoma arising in the wall of an epidermoid cyst present on the back for 20
      years. We emphasize the advisability of a close histologic examination of all
      cutaneous cysts that are seemingly benign in order to avoid incorrect diagnosis.

PMID- 11442599
TI  - Radiotherapy for genital extramammary Paget's disease in situ.
AB  - BACKGROUND: Radiotherapy as a first-choice treatment for extramammary Paget's
      (EMP) disease in situ has been seldom used. OBJECTIVE: To review the most
      relevant aspects of radiotherapy as first-choice treatment in selected cases of
      anogenital EMP disease in situ. METHODS: Two men with an age range of 71-79 years
      (mean age 75 +/- 5.6 years) with EMP disease in situ localized in the genital
      region were treated by means of X-rays of 100 kV, 440 cGy/day, 3 days a week over
      3 weeks until a total dose of 3960 cGy was completed. RESULTS: Complete
      regression of EMP disease in situ was observed in both patients after radical
      radiation therapy and neither local recurrences nor internal malignancies have
      been documented. CONCLUSION: Radiotherapy is a curative treatment in selected
      cases of EMP disease in situ affecting large areas of the anogenital region.

PMID- 11442600
TI  - Subungual osteochondroma: a case report.
AB  - Osteochondromas are among the most common bone tumors of the foot. However, they
      rarely occur in subungual locations. Clinically they appear as slow-growing
      masses causing deformity of the overlying nail. Here we present a case of
      subungual osteochondroma with characteristic clinical, radiologic, and
      histopathologic features. The lesion was successfully treated by total excision.

PMID- 11442601
TI  - Single-handed needle holder loading: a safer and more efficient cuticular stitch.
AB  - BACKGROUND: Needle sticks are one of the most common and feared occupational
      hazards that surgeons face. OBJECTIVE: To devise a safer and more efficient
      suturing method. METHODS: A cuticular stitch that minimizes direct contact with
      the needle is described. The literature is searched for similar suturing methods.
      RESULTS: Decreased direct contact with the needle lowers the risk for inadvertent
      sticks. Efficiency is improved when superfluous steps are eliminated from the
      suturing technique. CONCLUSION: Single-handed needle holder loading enhances
      safety while optimizing efficiency during the placement of cuticular stitches.

PMID- 11442602
TI  - Vertical harvesting in hair transplantation.
AB  - BACKGROUND: There are several methods for harvesting from donor area, including
      punch graft, multiple bladed knife, or single bladed knife excision followed by
      excision of an ellipse. Vertical harvesting is excellent for avoiding follicular
      transections because of complete visualization of the angle of the hair exiting
      the scalp. Also, the donor area is easier to visualize because of rock-hard
      tumescence achieved during the totality of procedure. Only an experienced surgeon
      using a multiple bladed knife would have fewer follicular transections.
      OBJECTIVE: Optimal yield of the donor area: ie, minimal transection, thus less
      hair follicle transection. METHOD: Vertical harvesting of slivers of hair
      measuring 0.75-1.85 cm in height, and 3-4 millimeters in width using #10 solitary
      bladed knife and Optivisor (as magnification). RESULT: In our opinion, there is
      less transection of the follicular bulbs leading to an increase in yield.
      CONCLUSION: Patient comfort is maximized because the patient lies on one side.
      Another advantage is the reduced role of the technician, therefore requiring
      fewer technicians.

PMID- 11442603
TI  - Repair of large helical rim defect.

PMID- 11442605
TI  - Regarding temporal artery biopsy technique.

PMID- 11442606
TI  - Regarding tretinoin peeling.

PMID- 11442607
TI  - Islam, teaching dermatologic surgery, and porcine parts.

PMID- 11442608
TI  - Regarding appropriate delays in reconstructing large, deep, or extensive
      midfacial defects following surgical management of skin cancer.

PMID- 11442609
TI  - Commentary on HIV lipodystrophy.

PMID- 11442610
TI  - Current approaches to venous ulcers and compression.
AB  - BACKGROUND: Venous ulcers affect as many as 2.5 million people in the United
      States and can cause substantial pain and loss of function. OBJECTIVE: To review
      current approaches to venous ulcers and compression. METHOD: Treatment options
      that have been proposed in the literature are discussed utilizing the Cochrane
      library database, Medline, and the author's clinical experience. RESULTS:
      Diagnostic findings and management strategies for venous ulcers are reviewed.
      CONCLUSION: Good wound care and compression therapy will heal the majority of
      small venous ulcers of short duration. For ulcers that are slow to heal, other
      approaches such as venous surgery and grafting with conventional or bioengineered
      skin substitutes should be considered.

PMID- 11442611
TI  - Comparison of long-pulsed diode and long-pulsed alexandrite lasers for hair
      removal: a long-term clinical and histologic study.
AB  - BACKGROUND: Unwanted facial and body hair is a common problem, generating a high
      level of interest for treatment innovations. Advances in laser technology over
      the past several years has led to the development and distribution of numerous
      red and infrared lasers and light sources to address this issue. Despite the
      impressive clinical results that have been reported with the use of individual
      laser hair removal systems, long-term comparative studies have been scarce.
      OBJECTIVE: To compare the clinical and histologic efficacy, side effect profile,
      and long-term hair reduction of long-pulsed diode and long-pulsed alexandrite
      laser systems. METHODS: Twenty women with Fitzpatrick skin types I-IV and dark
      terminal hair underwent three monthly laser-assisted hair removal sessions with a
      long-pulsed alexandrite laser (755 nm, 2-msec pulse, 10 mm spot) and a long
      pulsed diode laser (800 nm, 12.5 msec or 25 msec, 9 mm spot). Axillary areas were
      randomly assigned to receive treatment using each laser system at either 25 J/cm2
      or 40 J/cm2. Follow-up manual hair counts and photographs of each area were
      obtained at each of the three treatment visits and at 1, 3, and 6 months after
      the final laser session. Histologic specimens were obtained at baseline,
      immediately after the initial laser treatment, and 1 and 6 months after the third
      treatment session. RESULTS: After each laser treatment, hair counts were
      successively reduced and few patients found it necessary to shave the sparsely
      regrown hair. Optimal clinical response was achieved 1 month after the second
      laser treatment, regardless of the laser system or fluence used. Six months after
      the third and final treatment, prolonged clinical hair reduction was observed
      with no significant differences between the laser systems and fluences used.
      Histologic tissue changes supported the clinical responses observed with evidence
      of initial follicular injury followed by slow follicular regeneration. Side
      effects, including treatment pain and vesiculation, were rare after treatment
      with either laser system, but were observed more frequently with the long-pulsed
      diode system at the higher fluence of 40 J/cm2. CONCLUSION: Equivalent clinical
      and histologic responses were observed using a long-pulsed alexandrite and a long
      pulsed diode laser for hair removal with minimal adverse sequelae. While long
      term hair reduction can be obtained in most patients after a series of laser
      treatments, partial hair regrowth is typical within 6 months, suggesting the need
      for additional treatments to improve the rate of permanent hair removal.

PMID- 11442612
TI  - Photorejuvenation for Asian skin by intense pulsed light.
AB  - BACKGROUND: Dermabrasion and deep chemical peeling are used in the treatment of
      photoaged skin. These ablative procedures are effective enough to produce a
      certain improvement but have often caused postinflammatory hyperpigmentation
      among Asian patients. To avoid such adverse effects, a new, nonablative procedure
      has been sought. OBJECTIVE: To determine the effectiveness of photorejuvenation
      for Asian skin using intense pulsed light (IPL). The specific parameters used,
      improvement ratios, side-effects, and downtime required are also discussed.
      METHODS: Ninety-seven patients were treated for photoaging using IPL. The cutoff
      filters of 550 nm and 570 nm were utilized for three to six treatments at
      intervals of 2 to 3 weeks. RESULTS: Treatment results were evaluated and rated by
      both patients and physicians at the end of the third treatment based on
      improvement in pigmentation, telangiectasia, and skin texture. A combined rating
      of "good" or "excellent" was given to more than 90% of the patients for
      pigmentation, more than 83% for telangiectasia, and more than 65% for skin
      texture. There were some minor complications in four cases: one had erythema that
      continued to the next day and three had minor blisters leaving no marks.
      CONCLUSION: Photorejuvenation using IPL is a completely safe and effective
      procedure even for Asian skin. It will be increasingly used for skin rejuvenation
      in the future.

PMID- 11442613
TI  - The effect of cold air cooling on 585 nm pulsed dye laser treatment of port-wine
      stains.
AB  - BACKGROUND: The use of cryogen spray cooling in the course of dye laser treatment
      of port-wine stains has established itself in recent years because of its good
      analgesic and epidermally protective effects. The disadvantages of this kind of
      evaporative cooling are the cost and, in the case of dichlorodifluoromethane, the
      effects on the ozone layer. Cold air is an innovative cooling method that costs
      nearly nothing to use, is environmentally friendly, and can be easily adapted to
      existing laser systems. OBJECTIVE: To examine and evaluate cold air cooling as an
      alternative method of cooling in laser treatment. METHODS: In a prospective
      study, 13 patients (9 female, 4 male) with port-wine stains were treated with a
      pulsed dye laser (lambda = 585 nm, tau(p) = 450 microsec). In every case, either
      the entire area or a sample area of the port-wine stain was treated with cold air
      cooling on 50% of the surface and without on the other 50%. Clearance, analgesia,
      and adverse and concomitant effects were assessed. RESULTS: In nine patients
      (69%) there were similar results in terms of clearance. In four cases, better
      lightening results (in two patients) and worse lightening results (in two other
      patients) were achieved in the area treated with cold air. Nine of the patients
      (69%) felt that the laser impulses accompanied by cold air were significantly
      less painful. Adverse effects (purpura, erythema, edema) and concomitant effects
      (hypopigmentation, hyperpigmentation, scars) were much less marked in the cooled
      areas. CONCLUSION: Cold air is a safe and effective alternative to cryogen spray
      cooling. It is easy to use, economical, and environmentally friendly. Continuing
      studies are necessary to determine if there are interactions which affect the
      tissue.

PMID- 11442614
TI  - Gross and microscopic findings in patients undergoing microdermabrasion for
      facial rejuvenation.
AB  - BACKGROUND: Microdermabrasion (MDA) is a new procedure used for the treatment of
      cosmetic problems, particularly to combat photoaging and intrinsic aging. Though
      excellent clinical improvement has been well documented, histologic support is
      limited. OBJECTIVE: To determine if microscopic changes correlate with clinical
      improvement and to examine the depth of penetration compared to chemical peels.
      METHODS: Seven women were submitted to five MDA sessions at weekly intervals.
      Skin biopsies were performed in all of them, before and after the treatment.
      Clinical and photographic assessments were recorded weekly. Data concerning skin
      features, including oiliness, thickness, dilated pores, and general appearance,
      were all assessed. Microscopic improvement of changes associated with cutaneous
      aging in the epidermis and dermis where all assessed. For statistical analysis, a
      t-test for small samples was utilized. RESULTS: All the patients showed clinical
      and microscopic improvement in all of the parameters assessed. The t-test for
      small samples showed a P <.05. CONCLUSION: MDA is a good alternative for facial
      rejuvenation. Improvements in both clinical and microscopic parameters are
      readily demonstrable.

PMID- 11442615
TI  - Prevention of hypertrophic scars and keloids by the prophylactic use of topical
      silicone gel sheets following a surgical procedure in an office setting.
AB  - BACKGROUND: Topical silicone gel sheeting has been used for more than 20 years to
      help reduce the size of hypertrophic scars and keloids. Its clinical efficacy and
      safety is well established. OBJECTIVE: To determine whether topical silicone gel
      sheeting can be used to prevent hypertrophic scars and keloids from forming
      following dermatologic skin surgery. METHODS: Patients undergoing skin surgery
      were stratified into two groups: those with no history of abnormal scarring (low
      risk group) and those with a history of abnormal scarring (high-risk group).
      Following the procedure, patients within each group were randomized to receive
      either routine postoperative care or topical silicone gel sheeting (48 hours
      after surgery). Patients were followed for 6 months. RESULTS: In the low-risk
      group, there were no statistical differences between individuals using routine
      postoperative care or using topical silicone gel sheets. In the high-risk group,
      there was a statistical difference (39% versus 71%) between patients who did not
      develop abnormal scars and used topical silicone gel sheeting and patients who
      developed abnormal scars after routine postoperative treatment. Those individuals
      having a scar revision procedure also showed a statistical difference if topical
      silicone gel sheeting was used following surgery. CONCLUSION: Topical silicone
      gel sheeting, with a 20-year history of satisfaction in dermatology, now appears
      to be useful in the prevention of hypertrophic scars and keloids in patients
      undergoing scar revision.

PMID- 11442616
TI  - The role of frozen storage in preserving adipose tissue obtained by suction
      assisted lipectomy for repeated fat injection procedures.
AB  - BACKGROUND: The injection of autologous free fat obtained by suction-assisted
      lipectomy for the correction of soft tissue defects is a common procedure in
      plastic surgery. However, unpredictable partial absorption of the injected fat
      often necessitates repeated procedures. OBJECTIVE: To examine the role of frozen
      storage as a means of preserving the fat obtained by suction-assisted lipectomy
      for repeated procedures. METHODS: Human adipose tissue obtained by suction
      assisted lipectomy was stored in a domestic refrigerator at -18 degrees C for 2
      weeks. After thawing, the fat was injected into nude mice. In the control group,
      the fat was injected immediately after the harvesting procedure. Grafts were
      dissected out and compared 15 weeks postinjection. RESULTS: Injected fat survived
      in both study and control groups. No significant differences were found between
      fat graft weight and volume, or in any of the histologic parameters examined.
      CONCLUSION: Fat obtained by suction-assisted lipectomy may be preserved for
      future use by freezing.

PMID- 11442617
TI  - Artificial skin for closure and healing of wounds created by skin cancer
      excisions.
AB  - BACKGROUND: A dermal regeneration template indicated for life-threatening third
      degree burn injuries is a product with potential application to smaller wounds to
      aid in healing and closure of complex excision sites. OBJECTIVE: To assess the
      effectiveness of dermal regeneration template for closure of skin cancer excision
      sites that would have otherwise required complicated closures. METHODS: Five
      patients, 61-84 years old, with skin cancer surgery yielding a total of six
      wounds were treated with the dermal regeneration template to close and heal their
      wounds. RESULTS: Four of five patients had complete healing (five of six wounds)
      with cosmetically acceptable results. The one treatment failure was application
      of the dermal regeneration template over exposed skull where inadequate neodermis
      formed. Successful healing was observed in five complex skin cancer excision
      sites including two wounds in previously irradiated grafted skin, a large and
      deep temporal defect, a wide excision in the supraclavicular region, and an
      excision down to cartilage on the antihelix of the ear. No infections were noted,
      although in four of five patients prophylactic oral antibiotics (either
      erythromycin or cephalexin) were prescribed postoperatively for 1-2 weeks.
      CONCLUSION: The product simplified wound care, subjectively appeared to decrease
      pain and postoperative bleeding, and yielded cosmetically acceptable wound
      repair. Autografting was not necessary; wounds healed in 2-4 months by
      epithelialization over neodermis after removal of the silicone layer.
      Furthermore, the product was a convenient long-term dressing and healing device
      for wounds where complex repairs, autografts, and/or flaps would otherwise be
      considered for closure.

PMID- 11442618
TI  - Nasolabial V-Y advancement for closure of the midface defects.
AB  - BACKGROUND: V-Y subcutaneous advancement flaps receive an excellent blood supply
      from subcutaneous tissue and are ideal for use on the face. Also it is
      advantageous cosmetically compared to other local flaps. OBJECTIVE: Nasolabial V
      Y advancement flaps are very useful in closing defects of the midface region
      after tumor resection. METHODS: Our experience with nasolabial V-Y flaps in 22
      patients is reported. The average defect size was 2.4 cm x 3.2 cm. RESULTS: Minor
      flap necrosis occurred in one patient and simple lower eyelid ectropion in
      another. CONCLUSION: Nasolabial V-Y advancement flap is a simple and satisfactory
      alternative for closing relatively large defects in the midface when compared
      with other methods such as skin graft and rotation or transposition flaps. It is
      easy to design, reliable, and offers good cosmetic results.

PMID- 11442619
TI  - Trichoblastic carcinoma: a report of two cases of a deeply infiltrative
      trichoblastic neoplasm.
AB  - BACKGROUND: Trichoblastoma is a benign neoplasm with primitive hair follicle
      differentiation. The tumor is characterized by nests and cords of epithelial
      cells in an organized relationship with stroma. Some of the epithelial cells
      resemble follicular germ and other cells show follicular sheath differentiation.
      The neoplasm is symmetrical and well circumscribed. In addition, cytologic
      examination shows no atypia. Concept of its malignant counterpart is poorly
      understood. OBJECTIVE: We report two trichoblastic neoplasms that show histologic
      features of malignancy. METHODS: Skin biopsies from the lip region of a 53-year
      old female and a 74-year-old male who had presented with the neoplasms in that
      location for several years were reviewed. Excised specimens measured 2 x 1 x 1 cm
      and 1.6 x 0.7 x 0.8 cm respectively. RESULTS: The histologic sections revealed
      locally aggressive neoplasms showing prominent differentiation towards hair germ
      and follicular sheath with formation of papillary mesenchymal bodies, follicular
      bulb-like structures, small keratin cysts and rare malformed hair shaft. The
      neoplasm showed asymmetry of architecture and massive subcutaneous and muscular
      infiltration. CONCLUSION: With demonstration of these two cases and references of
      few other reported cases we raise the possibility of existence of trichoblastic
      carcinoma that is distinct from basal cell carcinoma.

PMID- 11442620
TI  - Multiple basal cell carcinomas developed after radiation therapy for tinea
      capitis: a case report.
AB  - Development of skin neoplasms is the most important complication of radiation
      therapy. There are contradictive reports about the type of these neoplasms.
      Squamous cell carcinomas are considered the most frequent tumors arising on
      chronic radiodermatitis areas, but recent studies have demonstrated that the type
      of neoplasm occurring in response to ionizing radiation exposure depends on
      several factors. Herein we report a patient who had received low-dose radiation
      for the treatment of tinea capitis and developed multiple basal cell carcinomas
      in the radiated areas after a long latent period of 53 years.

PMID- 11442621
TI  - Treatment of "Cyrano" angioma with pulsed dye laser.
AB  - BACKGROUND: Hemangiomas of the nasal tip, the so-called Cyrano nose, are often
      deep, disfiguring, and persistent. OBJECTIVE: To evaluate the effect of treatment
      with pulsed dye laser on Cyrano nose. METHODS: A 3-month-old boy with hemangioma
      of the nasal tip of 1-months duration underwent six sessions of pulsed dye laser
      treatment with a 7 mm collimated beam at fluences of 5.75-6.5 J/cm2, 6 weeks
      apart. RESULTS: Initial improvement was noted after two treatments, and the
      lesion showed a marked reduction in size and improvement in color over a total
      treatment period of 9 months. CONCLUSION: Treatment with the 585 nm pulsed dye
      laser should be considered in the management of infants with mild to moderate
      degrees of nasal tip hemangiomas since it effectively reduces the lesions with
      minimal adverse effects.

PMID- 11442622
TI  - Pigmented Bowen's disease (squamous cell carcinoma in situ): a mimic of malignant
      melanoma.
AB  - BACKGROUND: Darkly pigmented individuals may manifest unusual or uncharacteristic
      presentations of various skin conditions, including heavy pigmentation of
      cutaneous tumors. OBJECTIVE: To increase the awareness of an unusual presentation
      of Bowen's disease in a darkly pigmented individual. METHODS: We report the case
      of a 52 year old black woman that presented with a lesion clinically consistent
      with malignant melanoma. However, histopathologic examination revealed pigmented
      Bowen's disease. RESULTS: A biopsy is almost always indicated to confirm the
      diagnosis of lesions in darkly pigmented individuals. CONCLUSION: This case is
      presented to reinforce the idea that pigmented Bowen's disease should be
      considered in the differential diagnosis of malignant melanoma.

PMID- 11442623
TI  - Atrophic facial scars secondary to discoid lupus erythematous: treatment using
      the Erbium:YAG laser.
AB  - BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic inflammatory skin
      condition notorious for causing disfiguring scars and alopecia. We describe the
      case of a 66-year-old woman with a 25-year history of relapsing DLE who developed
      extensive cribriform scarring on her face. OBJECTIVE: To assess the safety and
      efficacy of laser resurfacing in the treatment of facial scars in DLE. METHODS:
      One patient was treated with an Er:YAG laser and followed for more than 2 years.
      RESULTS: The patient showed remarkable cosmetic improvement with no hypertrophic
      scarring and no reactivation of her disease. CONCLUSION: Er:YAG laser resurfacing
      may be safe and effective in the treatment of patients with DLE-induced atrophic
      scars.

PMID- 11442624
TI  - Neglected microcystic adnexal carcinoma: the second reported case in a black
      patient.
AB  - BACKGROUND: Microcystic adnexal carcinoma (MAC) is a histologically aggressive
      appendageal neoplasm that often pursues a beguilingly indolent clinical course.
      MAC has previously been reported only once in a black patient. OBJECTIVE: To
      present the second MAC ever recorded in a black patient. METHODS: We describe a
      MAC of substantial dimension occurring in a black patient. The literature was
      subsequently examined for MAC occurring in ethnic patients. RESULTS: This MAC is
      remarkable not only for its occurrence in a black patient, but also because it is
      one of the largest MACs ever recorded (8 cm), it occurs in a relatively less
      common site (scalp), and its latency period before diagnosis is the longest ever
      definitively documented (31 years). CONCLUSION: MAC is rare among non-Caucasians.
      Its relatively indolent clinical growth, especially in sites that are poorly
      accessible to patient observation, may lead to significant delay in diagnosis and
      treatment.

PMID- 11442625
TI  - Inverted pyramidal biopsy.
AB  - We describe a biopsy technique that is simple, rapid, and effective for numerous
      cutaneous lesions. The inverted pyramidal biopsy (IPB) creates an acute geometric
      tissue defect with an apex located in the dermis. A cosmetically pleasing result,
      while still providing adequate tissue to render a histologic description and
      diagnosis, is obtained. The technique can also be employed to remove a host of
      benign lesions, including dermatofibroma, fibrous papules, and chalazion, among
      others.

PMID- 11442626
TI  - Surgical treatment for vitiligo through hair follicle grafting: how to make it
      easy.

PMID- 11442627
TI  - Total lower lip reconstruction with innervated muscle-bearing flaps: a
      modification of the Webster flap.
AB  - BACKGROUND: Mohs surgery and other surgical techniques are used for the removal
      of squamous cell carcinoma of the lower lip and may leave a large defect in the
      vermilion and underlying tissue. When nearly the entire lower lip is excised,
      reconstruction of this defect is a challenge. Repair requires the matching of
      vermilion color, maintenance of oral sphincter function and mouth opening size,
      and retention of sensation. Several techniques have been suggested. We present a
      modification of the Webster flap for total lower lip reconstruction using
      innervated muscle-bearing flaps. OBJECTIVE: To present a surgical technique for
      the reconstruction of total lower lip defects after excision of squamous cell
      carcinoma. METHODS: Innervated muscle-bearing flaps are used and demonstrated in
      one case. The surgical technique is discussed in detail. RESULTS: The
      reconstructive results were excellent. There were no postoperative complications.
      CONCLUSION: The use of innervated muscle-bearing flaps is a useful and effective
      option for the reconstruction of total lower lip defects.

PMID- 11442628
TI  - Repair of a large lateral forehead defect.

PMID- 11442629
TI  - Undermining definitions, concepts, and execution.

PMID- 11442630
TI  - Yeast Saccharomyces cerevisiae has two cis-prenyltransferases with different
      properties and localizations. Implication for their distinct physiological roles
      in dolichol synthesis.
AB  - BACKGROUND: Dolichol is a family of long-chain polyprenols, which is utilized as
      a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). We
      have identified a key enzyme of the dolichol synthesis, cis-prenyltransferase, as
      Rer2p from Saccharomyces cerevisiae. We have also isolated a multicopy suppressor
      of an rer2 mutant and named it SRT1. It encodes a protein similar to Rer2p but
      its function has not been established. RESULTS: The cis-prenyltransferase
      activity of Srt1p has been proved biochemically in the lysate of yeast cells
      lacking Rer2p. The polyprenol product of Srt1p is longer in chain length than
      that of Rer2p and is not sufficiently converted to dolichol and dolichyl
      phosphate, unlike that of Rer2p. The subcellular localization of these two
      isozymes has been examined by immunofluorescence microscopy and by the use of GFP
      fusion proteins. Whereas GFP-Rer2p is localized to the continuous ER and some
      dots associated with the ER, GFP-Srt1p shows only punctate localization patterns.
      Immunofluorescence double staining with Erg6p, a marker of lipid particles in
      yeast, indicates that Srt1p is mainly localized to lipid particles (lipid
      bodies). RER2 is mainly expressed in the early logarithmic phase, while the
      expression of SRT1 is induced in the stationary phase. CONCLUSIONS: We have shown
      that yeast has two active cis-prenyltransferases with different properties. This
      result implies that the two isozymes have different physiological roles during
      the life cycle of the yeast.

PMID- 11442631
TI  - A member of the YER057c/yjgf/Uk114 family links isoleucine biosynthesis and
      intact mitochondria maintenance in Saccharomyces cerevisiae.
AB  - BACKGROUND: Two paralogs, YIL051c and YER057c, in the Saccharomyces cerevisiae
      genome are members of the YER057c/Yigf/Uk114 family, which is highly conserved
      among Eubacteria, Archaea and Eukarya. Although the molecular function of this
      protein family is not clear, previous studies suggest that it plays a role in the
      regulation of metabolic pathways and cell differentiation. RESULTS: Yil051cp is
      70% identical in amino acid sequence to Yer057cp, and differs in that the former
      is longer by 16 amino acids containing, in part, the mitochondrial targeting
      signal at the N-terminus of the protein. An HA-tagged protein of Yil051cp is
      localized strictly in mitochondria, while that of Yer057cp is found in both
      cytoplasm and nucleus. Disruption of YIL051c (yil051cDelta) resulted in severe
      growth retardation in glucose medium due to isoleucine auxotroph, and no growth
      in glycerol medium due to the loss of mitochondria. An extract prepared from
      yil051cDelta cells showed no transaminase activity for isoleucine, while that for
      valine or leucine was intact. Haploid yil051cDelta cells newly isolated from the
      YIL051c/yil051cDelta hetero-diploids gradually lost mitochondrial DNA within 24 h
      in the absence of, but not in the presence of, an isoleucine. Mutants either
      requiring leucine (leu2-112) or isoleucine-valine (bat1Delta, bat2Delta) in a
      YIL051c background showed no changes in mitochondrial DNA maintenance in the
      absence of requirements. CONCLUSIONS: Based on these results, we named Yil051c as
      Ibm1 (Isoleucine Biosynthesis and Mitochondria maintenance1) and concluded that:
      (i) Ibm1p determines the specificity of isoleucine biosynthesis, probably at the
      transamination step, (ii) Ibm1p is required for the maintenance of mitochondrial
      DNA when isoleucine is deficient, and (iii) Isoleucine compensates for the lack
      of Ibm1p. Taken together, Ibm1p may act as a sensor for isoleucine deficiency as
      well as a regulator determining the specificity for branched amino acid
      transaminase.

PMID- 11442632
TI  - MST1-JNK promotes apoptosis via caspase-dependent and independent pathways.
AB  - BACKGROUND: MST1 is an upstream kinase of the JNK and p38 MAPK pathways whose
      expression induces apoptotic morphological changes such as nuclear condensation.
      During apoptosis, caspase cleavage of MST1 removes a C-terminal regulatory
      domain, increasing the kinase activity of the MST1 N-terminal domain. Downstream
      pathways of MST1 in the induction of apoptosis remain to be clarified. RESULTS:
      In this study, we found that the expression of MST1 resulted in caspase-3
      activation. Therefore, MST1 is not only a target of caspases but also an
      activator of caspases. This caspase activation and apoptotic changes occur
      through JNK, since the co-expression of a dominant-negative mutant of JNK
      inhibited MST1-induced morphological changes as well as caspase activation. In
      contrast, neither a dominant-negative p38 nor the p38 inhibitor SB203580
      inhibited them. MST1 induced nucleosomal DNA fragmentation, which was suppressed
      by caspase inhibitors or ICAD (Inhibitor of Caspase-Activated DNase).
      Surprisingly, however, other changes such as membrane blebbing and chromatin
      condensation were not inhibited by caspase inhibitors. CONCLUSION: These results
      suggest that MST1 most likely promotes two events through JNK activation; first,
      MST1 induces the activation of caspases, resulting in CAD-mediated DNA
      fragmentation, and second, MST1 induces chromatin condensation and membrane
      blebbing without utilizing downstream caspases.

PMID- 11442633
TI  - Identification and characterization of DAlk: a novel Drosophila melanogaster RTK
      which drives ERK activation in vivo.
AB  - BACKGROUND: The mammalian receptor protein tyrosine kinase (RTK), Anaplastic
      Lymphoma Kinase (ALK), was first described as the product of the t(2;5)
      chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of
      ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo
      role for this orphan insulin receptor family RTK has been described. RESULTS: We
      describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to
      band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes
      a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK
      but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK
      reveals that the ALK family of RTKs contains a newly identified MAM domain within
      their extracellular domains. Like its mammalian counterpart, DAlk appears to be
      expressed in the developing CNS by in situ analysis. However, in addition to
      expression of DAlk in the Drosophila brain, careful analysis reveals an
      additional early role for DAlk in the developing visceral mesoderm where its
      expression is coincident with activated ERK. CONCLUSION: In this paper we
      describe a Drosophila melanogaster Alk RTK which is expressed in the developing
      embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk
      RTK pathway in Drosophila. We show that ERK participates in this pathway, and
      that it is activated by DAlk in vivo. Expression patterns of dALK, together with
      activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway,
      leading to ERK activation in the developing visceral mesoderm.

PMID- 11442634
TI  - Sendai virus C protein physically associates with Stat1.
AB  - BACKGROUND: The P/C gene of the Sendai virus (SeV), a member of the family
      Paramyxoviridae, encodes C protein, which plays a crucial role in counteracting
      the antiviral effect of interferon (IFN). The C protein blocks IFN signalling to
      prevent the activation of IFN stimulated genes. However, its underlying molecular
      mechanism remains to be defined. RESULTS: Signal transducer and activator of
      transcription 1 (Stat1) is a critical component of IFN-alpha/beta and IFN-gamma
      signalling. We found that both unphosphorylated Stat1 and tyrosine-phosphorylated
      (pY) Stat1 were present in a form of aberrant high molecular weight complexes
      (HMWCs) of over 2 MDa in infected cell extracts under low-salt conditions. Of
      recombinant vaccinia viruses carrying each SeV gene, only those expressing the C
      gene induced Stat1-HMWC. SeV infected cell extracts further displayed an in vitro
      ability to convert the pY-Stat1 homodimer to pY-Stat1-HMWC. This cell extract
      activity was not seen after removal of the C protein from the extracts. C protein
      was therefore involved in the formation of HMWCs. The HMWCs decomposed into
      smaller complexes in a high-salt buffer, and under this stringent (high-salt)
      condition, as well as a physiological (isotonic) condition, both unphosphorylated
      Stat1 and pY-Stat1 were co-precipitated with anti-C antibody. CONCLUSION: The C
      protein physically associates with Stat1. This suggests that SeV C protein
      directly targets Stat1 for inhibitory control on the transcriptional activation
      of IFN stimulated genes.

PMID- 11442635
TI  - Diverse gene expression and function of semaphorins in developing lung: positive
      and negative regulatory roles of semaphorins in lung branching morphogenesis.
AB  - BACKGROUND: Previously, we reported that Sema3A, one of the secreted repulsive
      axon guidance molecules, CRMP (collapsin response mediator protein)-2, a putative
      intracellular signalling molecule for Sema3A and Sema3A receptor neuropilin-1 are
      expressed in the developing lung. Sema3A inhibits branching morphogenesis of
      embryonic lung in organ culture. RESULTS: We examined the gene expression of
      Sema3A, Sema3C, Sema3F and their receptors, NP-1, NP-2 and plexin-A1 by in situ
      hybridization. Transcripts of all six genes were detected in mouse lung from
      embryonic day E11.5 to E17.5, and displayed highly specific spatiotemporal
      distributions. The distribution of the receptor genes was detected in patterns
      which were consistent with known receptor usage of the semaphorins. In contrast
      to Sema3A, we found that the other class 3 semaphorins, Sema3C and Sema3F,
      stimulated branching morphogenesis. This stimulatory effect of Sema3C or Sema3F
      was accompanied by a moderate increase in the incorporation of bromodeoxyuridine
      (BrdU) into DNA in the terminal epithelial cells. CONCLUSION: The coordinated
      expression patterns of different semaphorins and their receptors, together with
      the specific activities affecting branching morphogenesis, suggest that the
      semaphorins act as both positive and negative regulators of branching
      morphogenesis in the developing lung.

PMID- 11442636
TI  - Guidelines on the diagnosis, management and prevention of hepatitis in
      haemophilia.

PMID- 11442637
TI  - Lack of evidence for increased inhibitor incidence in patients switched from
      plasma-derived to recombinant factor VIII.
AB  - De novo inhibitor development is a rare event in PTPs switched from pdFVIII to
      rFVIII. Based on previously published data of clinical studies a change in FVIII
      product is unlikely to provoke inhibitor formation.

PMID- 11442638
TI  - Treatment of haemophilia in the United Kingdom 1981-1996.

PMID- 11442639
TI  - An approach to study the viral safety of plasma-derived products in previously
      treated, non-infected patients.
AB  - Using the polymerase chain reaction (PCR), we designed a study concept to
      evaluate the safety of plasma derivatives in previously treated patients who are
      non-infected by the specific viruses studied. Several product lots can be studied
      in a single patient, with a study period for each lot of 3 months. In the present
      study 19 patients were included for treatment with Baxter Hyland Immuno's PCR
      screened factor VIII concentrate Immunate (n=7), factor IX concentrate Immunine
      (n=10), the by-passing agent FEIBA plus Immunine (n=1), and the protein C
      concentrate Ceprotin (n=1). PCR testing for hepatitis B, C or HIV genomic
      material in patient samples was done as well as serological testing. All patients
      remained negative for the tested markers. All seven Immunate patients completed
      three treatment periods with three different lots of the study drug. The median
      study period was 282 days and the median dose 115 000 units, with a median of 115
      exposure days. Five of the 10 Immunine patients completed three treatment periods
      and four patients, two treatment periods. One Immunine patient was discontinued
      from the study for reasons unrelated to the study drug administration. The median
      study period was 305 days and the median total dose 82 200 units, with a median
      of 88 exposure days. Our study presents a new design to approach the evaluation
      of viral safety of new plasma derivatives in previously treated, non-infected
      patients (NIPs) and offers several advantages over the currently recommended
      studies using testing for serological markers of infection in previously
      untreated patients (PUPs).

PMID- 11442640
TI  - Purity of factor VIII product and incidence of inhibitors in previously untreated
      patients with haemophilia A.
AB  - It has been suggested that ultrapure clotting factor products carry a greater
      risk for inhibitor development in patients with haemophilia. We compared the
      incidence of inhibitors in 59 previously untreated patients (PUPs) with severe
      haemophilia (endogenous factor VIII < 0.01 U L-1) A, who were initially treated
      with cryoprecipitate or intermediate purified products, with that in 22 patients
      exclusively treated with monoclonally purified and recombinant factor VIII.
      Persistent inhibitors were those with 1 Bethesda unit per mL or more, on more
      than one occasion, combined with a decrease in recovery. Incidences of persistent
      inhibitors were 17% (10/59) for patients who were treated with cryoprecipitate or
      intermediate-purity products and 9% (2/10) for monoclonally purified and
      recombinant factor VIII. Transient inhibitors appeared to develop earlier during
      treatment with ultrapure products as compared to treatment with intermediate/low
      purity products. In conclusion, ultrapure products appear not to carry a higher
      risk for inhibitor development.

PMID- 11442641
TI  - Influence of von Willebrand factor on the reactivity of human factor VIII
      inhibitors with factor VIII.
AB  - In order to determine the difference in reactivity of factor (F) VIII inhibitors
      against the FVIII/von Willebrand factor (vWF) complex and against vWF-deficient
      FVIII, we investigated a panel of 10 antibodies to FVIII from multitransfused
      individuals with severe haemophilia A and other pathologies. Immunoblotting of
      purified FVIII and purified thrombin-cleaved FVIII revealed that in all cases
      inhibitor epitopes could be localized in the heavy chain (A2 subunit) while in
      four cases they were also present in the light chain. One of the FVIII inhibitors
      remained unclassified. The effect on FVIII:C of purified IgG from inhibitor
      plasmas was tested against a high purity FVIII/vWF concentrate and a monoclonally
      purified FVIII concentrate with only trace contents of vWF, by two different
      functional assays. Our results suggest that for those inhibitors showing A2 plus
      light chain (LC) reactivity, the IgG concentration required to inhibit 50% of
      FVIII activity in vitro is higher for the FVIII/vWF complex than for the vWF
      deficient FVIII. We conclude that there might be a protective role of vWF (at
      least in vitro) against FVIII inhibitors with A2 and LC subunit specificity.

PMID- 11442642
TI  - von Willebrand factor in factor VIII concentrates protects against neutralization
      by factor VIII antibodies of haemophilia A patients.
AB  - We investigated the neutralization activity of factor VIII (FVIII) antibodies of
      12 haemophilia A patients, acquired during treatment with plasma-derived FVIII
      concentrates. All plasma samples, drawn in a clinically stable situation before
      any immunotolerance treatment, contained anti-A2 domain and anti-light-chain
      FVIII antibodies. In nine patients' plasmas, containing relatively high amounts
      of FVIII light-chain antibodies (53-96%), a higher neutralization activity was
      found against recombinant FVIII concentrate (Recombinate) than against plasma
      derived von Willebrand factor (vWF)-containing concentrate (Haemoctin SDH). No
      difference in neutralization of the two concentrates was found in two patients'
      plasmas with almost equal content of FVIII light- and heavy-chain antibodies, or
      one plasma with predominantly heavy-chain antibodies. These results suggest that
      haemophilia A patients with relatively high amounts of FVIII light-chain
      antibodies in plasma might benefit by infusion of FVIII concentrates containing
      vWF because vWF appears to have some protective effect on FVIII. This hypothesis
      should be tested by a clinical study.

PMID- 11442643
TI  - Site and type of mutations in the factor VIII gene in patients and carriers of
      haemophilia A.
AB  - Haemophilia A is an X-linked bleeding disorder caused by reduced or absent FVIII
      (FVIII) protein caused by mutations in the FVIII gene. We have used Southern
      blotting and chemical mismatch analysis (CMA) to identify the mutations causing
      haemophilia A in 59 local or referred patients or carriers of haemophilia A.
      Southern blot analysis of 87 families with FVIII : C < 5% identified 31 as
      positive for the intron 22 inversion. Analysis of 19 of the inversion-negative
      families and a further nine families with mild or moderate haemophilia A by CMA
      resulted in the identification of a heterogeneous spectrum of mutations in the
      FVIII gene comprising 21 single base-pair substitutions and nine deletions.
      Seventeen of the base-pair substitutions are missense, two nonsense, and two are
      splice-site mutations. Two patients were found to have compound mutations with
      two mutations identified on a single X chromosome. Six of the point mutations and
      six of the deletions have not been reported previously in the haemophilia A
      mutation database. Unusually, a missense mutation, as well as deletion and splice
      site mutations, was found to be associated with exon-skipping events.

PMID- 11442644
TI  - Barriers to compliance with prophylaxis therapy in haemophilia.
AB  - Prophylaxis, or the practice of routine replacement infusions of clotting factor
      concentrate in persons with severe haemophilia, is a demanding medical regimen.
      Prophylactic infusions require direct venepuncture or sterile entry into a
      central venous access device on a regular basis. A telephone survey was conducted
      to elicit information regarding the barriers to compliance with prophylaxis. The
      Mountain States Regional Haemophilia and Thrombosis Center has recommended
      prophylaxis to 52 male patients with haemophilia A or B. The haemophilia nurse
      attempted to contact all of these patients or their parents, and contact was made
      with 38 (73.1%) of them. Respondents were asked about the following issues: their
      decision to initiate prophylaxis; their self-rated compliance; the challenges,
      barriers, and facilitators of prophylaxis; and their perceived value of the
      therapy. Four patients (10.5%) elected not to begin prophylaxis. Of the 34
      persons who began prophylaxis, 20 respondents (58.8%) rated their compliance as
      excellent. Nearly one-third of the families with excellent compliance (giving 75
      100% of prescribed infusions) stated that the time-consuming nature of
      prophylaxis was the most significant challenge of the regimen. In addition, 58.3%
      of the families that gave less than the prescribed number of infusions reported
      that the time commitment was the primary reason for missing infusions. Knowledge
      of the benefits of prophylaxis was the primary facilitator of compliance for
      44.1% of families. Ninety-seven percent of respondents rated prophylaxis as very
      valuable. These data show that despite the known benefits of prophylaxis, it is a
      demanding medical regimen, and compliance is imperfect. In addition, this study
      underscores the importance of providing continuing support and education for
      patients and families who are implementing prophylaxis.

PMID- 11442645
TI  - Improvement of patient education and information: development of a patient's
      information dossier.
AB  - The demand for patient information in modern medical care is increasing and sound
      information for patients is becoming a necessity. For haemophilia patients,
      information about their disease and its complications is already widely
      available. In order to increase the organization of this information, a 'Patient
      Information Dossier' (PID) and communication check lists were developed at the
      Dutch National Hemophilia Center, the Van Creveldkliniek, in cooperation with the
      Department of Patient Education of the University Medical Center Utrecht. The PID
      has an unique double function: (1) it contains patient tailored information about
      the practical facts of hospital care; and (2) it provides a communication
      checklist used by various members of the comprehensive care team, in order to
      supply patients with more uniform information. In order to gain a better insight
      of the gaps in information supply, according to patients and healthcare workers,
      the Department of Patient Education formulated a questionnaire. The PID itself
      was written by a study group consisting of members of the comprehensive care
      team. The entire process was developed, edited and coordinated by an advisor of
      the Department of Patient Education. The above-mentioned study group developed a
      specific PID on haemophilia care. Its 10 chapters provide information and
      guidelines, and advise patients where to find more information about this
      subject. Each chapter includes a checklist for patients, enabling them to prepare
      subjects for discussion during clinical visits. The team also developed a
      communication checklist to be used by various team members during a patient's
      visit to the clinic, as well as specific checklists covering the possible problem
      subjects of the PID. The PID is the lifelong property of the patient, and can be
      used during each visit to the clinic. The PID was implemented in February 2000,
      and within 4 months, was distributed among 200 patients visiting the Van
      Creveldkliniek. Evaluation by use of a questionnaire showed that most patients
      found the information in the PID sufficient and in accordance with that which
      they had received previously.

PMID- 11442646
TI  - A new strategy for prenatal diagnosis in a sporadic haemophilia B family.
AB  - Although the quality of life for haemophiliacs has clearly improved in the last
      few years, haemophilia still remains a serious disorder justifying prenatal
      diagnosis (PD) and, if necessary, termination. Because chorionic villus sampling
      (CVS) is performed in the first trimester of pregnancy, an increasing number of
      carriers are interested in this test. It has been shown that waiting for the
      results is particularly distressing for pregnant women, therefore decreasing the
      diagnostic procedure time can be psychologically helpful. Here we report on PD in
      a sporadic haemophilia B family based on the direct identification of the
      pathogenic mutation in a CVS taken at the 12th gestational week. In order to
      hasten the results, we recovered DNA from a single villus fragment boiled in
      water and used it directly for PCR reaction. Conformation-sensitive gel
      electrophoresis (CSGE) was used to detect the mutation in the haemophilia carrier
      and in the foetus. This approach allowed us to obtain a diagnosis within 24 h of
      CVS, thus avoiding the long-term psychological effects on the pregnant woman.

PMID- 11442647
TI  - Mild haemophilia A discovered in a previously multi-operated 73-year-old man:
      characterization of a new mutation.
AB  - A mild haemophilia A (factor VIII [FVIII] 10%) was discovered in a 73-year-old
      man during the preoperative haemostasis tests before a total knee arthroplasty
      for treatment of degenerative senile arthropathy. No history of previous abnormal
      bleeding was noted in spite of several previous challenging surgical procedures.
      Acquired haemophilia was ruled out and no other cases of haemophilia were found
      in the family. The surgery was successfully performed under recombinant FVIII
      aimed at achieving an FVIII level above 60%. This therapy induced the transient
      appearance of low-titre FVIII antibodies. A still unpublished mutation within the
      exon 3 (Gly73Ala) was found with molecular studies. This case report underlines
      the importance of haemostasis tests before high-risk bleeding surgical procedures
      even in elderly patients without a past history of haemorrhagic tendency.

PMID- 11442648
TI  - Postpartum inhibitor to factor VIII: treatment with high-dose immunoglobulin and
      dexamethasone.
AB  - Spontaneous occurrence of an acquired inhibitor to factor VIII (FVIII) is a rare
      event. About 50% of cases are idiopathic. Among younger people, inhibitors are
      often found in the postpartum period. Treatment must be administered either to
      overcome haemorrhagic symptoms or to eradicate the inhibitor. Several approaches
      have been proposed for inhibitor eradication, based on immunosuppressive drugs
      such as corticosteroids, cyclophosphamide and azathioprine, with varying results.
      High-dose immunoglobulin (HDIg) has been recently proposed as first-line therapy.
      We report on four cases with acquired inhibitor to FVIII occurring 4-8 months
      after delivery. At diagnosis, inhibitor titre was < 5 Bethesda units mL(-1) (BU
      mL(-1)) in three cases and > 5 BU mL(-1) in one. Factor VIII coagulant activity
      (FVIII:C) was < 1 U dL(-1)> in three cases and 12 U dL(-1) in one. We treated the
      patients with HDIg (400 mg kg-1 day(-1) for 5 consecutive days) and dexamethasone
      (24 mg day(-1) for 5-7 consecutive days), administered at the same time. In three
      women, the inhibitor was suppressed in 2-50 weeks. After an off-therapy period
      ranging from 20 to 104 weeks, the FVIII:C was persistently normal and the
      inhibitor undetectable. The fourth woman remained unresponsive. In two cases,
      recombinant activated factor VII administration stopped the bleeding. Thus,
      intermediate- to high-dose dexamethasone and HDIg given at the same time could be
      a successful and safe therapeutic approach for a rapid and complete remission
      from the development of FVIII inhibitors.

PMID- 11442649
TI  - Acquired haemophilia in the elderly is a severe disease: report of five new
      cases.
AB  - Acquired haemophilia is a rare but life-threatening bleeding disease that can be
      observed in males or females at various ages. In the present study, we report on
      five cases of acquired factor (F) VIII inhibitors diagnosed in the elderly
      population over a period of 5 years between 1995 and 1999 in our hospital. The
      median age of the patients at the time of diagnosis was 76.2 years (66-92 years).
      In all cases, the diagnosis was suggested by mild to severe bleeding with no
      previous bleeding history. While the absence of associated conditions is
      frequently reported especially among the elderly, in our series an underlying
      disease was found in four out of the five cases: kidney tumour (two cases) and
      autoimmune disease (two cases). The bleeding was controlled in four patients
      using porcine FVIII (two cases) or recombinant FVIIa (two cases). The inhibitors
      were completely resolved in two patients (kidney tumour, GoodPasture syndrome) by
      treatment of the underlying disease. However, three patients died as direct or
      indirect consequence of having an inhibitor. Our series confirms and extends
      previous data reporting the complexity and severity of this disorder. Because
      bleeding is often severe, a prompt and correct diagnosis is required to provide
      adequate therapeutic options that take the advanced age of the patients into
      account.

PMID- 11442650
TI  - A case of chronic myelomonocytic leukaemia and factor XI deficiency with a
      circulating anticoagulant.
AB  - Inhibitors against factor XI (FXI) have been frequently described in patients who
      acquired inhibitors (due to auto-immune disorders, malignancies or infections),
      but less often in those with a congenital deficiency of this factor, who had
      received plasma infusions. The present report concerns one such inhibitor found
      in the plasma of a patient with chronic myelomonocytic leukaemia and infected by
      B19 parvovirus, who was neither a heterozygote nor a homozygote for FXI
      deficiency, and who had no bleeding tendency despite a very low FXI level. Taking
      this case into account, we discuss and present the clinical and biological
      features of acquired FXI deficiency caused by an inhibitor.

PMID- 11442651
TI  - Tai Chi Chuan for persons with haemophilia: commentary.

PMID- 11442652
TI  - Tai Chi Chuan for people with haemophilia.

PMID- 11442653
TI  - Induction of immune tolerance and suppression of anaphylaxis in a child with
      haemophilia B by simple plasmapheresis and antigen exposure: progress report.

PMID- 11442654
TI  - Novel therapeutic strategy for advanced prostate cancer using antisense
      oligodeoxynucleotides targeting anti-apoptotic genes upregulated after androgen
      withdrawal to delay androgen-independent progression and enhance
      chemosensitivity.
AB  - Progression to androgen-independence remains the main obstacle to improving
      survival for patients with advanced prostate cancer. In this review, findings are
      summarized that have recently been demonstrated to establish novel therapeutic
      strategy targeting several genes playing functionally important roles after
      androgen withdrawal and during androgen-independent progression. The authors
      initially characterized changes in gene expression after androgen withdrawal in
      the androgen-dependent Shionogi and LNCaP tumor models using cDNA arrays. Based
      on these results, they focused on genes highly upregulated after androgen
      ablation (i.e. bcl-2, bcl-xL, TR.PM-2, IGFBP-5), which have anti-apoptotic or
      mitogenic activities, and thereby confer a resistance to androgen withdrawal as
      well as cytotoxic chemotherapy. The authors further demonstrated the efficacy of
      an antisense oligodeoxynucleotide (ODN) strategy for patients with advanced
      prostate cancer through the inhibition of target gene expression, resulting in a
      delay in the progression to androgen-independence by enhancing apoptotic cell
      death induced by androgen ablation and chemotherapy. The authors also showed the
      effectiveness of combined antisense ODN therapy and cytotoxic chemotherapy by
      achieving additive or synergistic effects. These findings provide a basic
      significance for the design of clinical studies using antisense ODN either alone
      or in combination with chemotherapeutic agents in patients with advanced prostate
      cancer.

PMID- 11442655
TI  - A new portable measuring cup for voided volume.
AB  - When recording daily urine volumes for the frequency-volume chart, a patient must
      measure voided urine volume throughout the whole day. Unless the patient stays at
      home, the conventional 500-mL paper or plastic cup must be carried with at all
      times, which can be very embarrassing and troublesome for the patient, so a
      collapsible, portable measuring cup has been developed. To determine the
      measuring accuracy of the new cup, the visual estimate was compared with the
      actual volume. The cup was found to be a highly accurate and useful container for
      measuring voided urine volume.

PMID- 11442656
TI  - Chrono and clinical pharmacokinetic study of tacrolimus in continuous intravenous
      administration.
AB  - BACKGROUND: The circadian variation of clinical pharmacokinetics of tacrolimus in
      kidney transplant recipients receiving continuous intravenous administration has
      not been clarified. The aim of this study was to evaluate the circadian variation
      of this drug in continuous intravenous administration, with regard to the dosing
      scheme for conversion from intravenous to oral therapy. METHODS: The blood
      concentration-time curve was studied in 10 living-related kidney transplant
      recipients, aged 18-51 years (mean, 36.5 years), 1 day before operation for
      preoperative oral administration, the third postoperative day for continuous
      intravenous administration and the sixth postoperative day at the conversion from
      intravenous to oral therapy. RESULTS: Although the total body clearance of
      daytime was slightly higher than that of night-time, the intravenous tacrolimus
      infusion maintained an adequate therapeutic blood concentration for 24 h. There
      were significant differences between the preoperative and the postoperative state
      in the area under the curve, total body clearance and bioavailability for the
      oral administration. The mean absolute bioavailability was 17.7% in preoperative
      and 11.1% in postoperative state, respectively and a large interindividual
      variation was confirmed in this parameter, which was 7.0-27.2% for preoperative
      and 6.4-22.0% for postoperative area under the curve, respectively. CONCLUSION:
      This study proposes that intravenous administration is a safe and appropriate
      method to achieve the required blood concentration in patients with various
      tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus
      absorption was found to be variable between preoperative and postoperative states
      in identical patients, the conversion dosage cannot be calculated from
      preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood
      concentration monitoring is needed to ensure safe treatment.

PMID- 11442657
TI  - The prevalence of renal cell carcinoma: a nation-wide survey in Japan in 1997.
AB  - BACKGROUND: The present study was conducted to investigate the incidence of renal
      cell carcinoma by sex, age group and different regions in Japan. METHODS: The
      survey was conducted from the beginning of January 1997 to the end of December
      1997. A total of 1306 Institutions in all 47 prefectures throughout Japan were
      requested to register cases. RESULTS: There were 6358 persons with renal cell
      carcinoma, consisting of 4372 men and 1986 women. The age-specific incidence
      rates showed a peak in the age group of 65-70 years in both men and women. The
      crude incidence rates per 100 000 population for men and women were 7.1 and 3.1,
      respectively, and age-standardized incidence rates per 100 000 population for men
      and women were 4.9 and 1.8, respectively. The incidence rates in the Hokkaido
      region were significantly higher than in other regions (P < 0.05), among which
      there was no significant difference in incidence rates. CONCLUSIONS: The present
      study showed that the incidence rates of renal cell carcinoma in Japan were
      approximately the same as among Japanese in Los Angeles. The rates were, however,
      lower than North American and European countries, but higher than China, Central
      or South American countries and African countries. The reasons for the high
      incidence of renal cancer in the Hokkaido region are not entirely clear. Further
      epidemiologic research is required.

PMID- 11442658
TI  - Prognostic factors for survival and bladder recurrence in transitional cell
      carcinoma of the upper urinary tract.
AB  - BACKGROUND: Prognostic factors for survival in transitional cell carcinoma of the
      upper urinary tract have been extensively evaluated, but detailed analyses of
      patterns of bladder recurrence after surgery have been rare. METHODS: The outcome
      and tumor recurrence of 93 patients with transitional cell carcinoma of the upper
      urinary tract surgically treated between 1975 and 1999 were reviewed,
      retrospectively. Disease-specific survival by pathologic stage and grade were
      analyzed by the Kaplan-Meier METHOD: Prognostic factors for survival and bladder
      recurrence were examined by univariate and multivariate analysis. RESULTS: The 5
      year disease-specific survival rates of the patients with pTa, T1 and T2 were
      92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9%
      and the median survival of the pT4 cases was only 7 months. Bladder recurrence
      was seen in 40 cases and recurrences occurred within 1 year in 32 of these
      patients. The stage and grade of metachronous bladder tumors usually resembled
      those of primary tumors, but invasive recurrences were seen in 19% of recurrent
      cases with primary pTa, pT1 tumors. The significant prognostic factor for
      survival was pathologic stage (pT3, pT4), but no significant variables were
      detected for bladder recurrence by multivariate analysis. CONCLUSIONS: The
      prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is
      necessary. Invasive bladder recurrence occurred in 19% of patients with
      superficial primary tumors. As no significant prognostic variables for bladder
      recurrence were identified, careful follow up for bladder recurrence is important
      even if the primary tumors are non-invasive.

PMID- 11442659
TI  - M1 prostate cancer with a serum level of prostate-specific antigen less than 10
      ng/mL.
AB  - BACKGROUND: M1 prostate cancer, which is invasive, is usually associated with a
      serum level of prostate-specific antigen (PSA) greater than 10 ng/mL, but cases
      are occurring where the serum PSA level is less than this. The present study
      investigated the clinical and pathologic characteristics of these cases of M1
      prostate cancer. METHODS: Between April 1989 and March 1998, 167 cases of M1
      prostate cancer were diagnosed by transrectal needle biopsy and eight of these
      with a serum PSA level less than 10 ng/mL were investigated. The patients' ages
      ranged from 57 to 79 years (median, 73) and the serum PSA levels ranged from less
      than 4.0 to 9.8 ng/mL. In all cases except one, the distal metastasis was to
      bones only. All cases had received hormonal therapy as the initial therapy.
      Immunostaining of PSA, chromogranin A, neuron-specific enolase, carcinoembryonic
      antigen and vimentin were performed in five of the eight cases. RESULTS: Four
      cases were poorly differentiated, two were undifferentiated, one was a mixture of
      poorly differentiated and undifferentiated and one case was moderately
      differentiated. Of the five cases in the immunohistochemical study, three cases
      with an undifferentiated carcinoma component showed negative staining reactions
      for PSA and all cases were positive for carcinoembryonic antigen. Four of the
      patients died of prostate cancer. In two of these four cases, hormonal therapy
      was ineffective, but systemic chemotherapy and irradiation therapy had been
      moderately effective. The overall 3-year survival rate was 33.3%. CONCLUSIONS:
      The cases of M1 prostate cancer with a serum PSA less than 10 ng/mL are almost
      always poorly differentiated or undifferentiated and have a poor prognosis
      compared with the usual M1 prostate cancer. Because hormonal therapy is
      ineffective in these cases, systemic chemotherapy and irradiation therapy should
      be chosen as the initial therapy.

PMID- 11442660
TI  - One-stage urethroplasty for strictures: Nigerian experience.
AB  - PURPOSE: To analyze the effects on voiding and complications of one-stage
      urethroplasty for urethral stricture. METHODS: All patients who underwent one
      stage urethroplasty for stricture in two health institutions in Enugu, Nigeria,
      between January 1989 and December 1998, were included. The age of the patient,
      duration of symptoms and the cause of the stricture were noted. Retrograde
      urethrogram and, when necessary, micturating cystourethogram was done.
      Urethroplasty was either by substitution using pedicled penile skin flap or by
      end-to-end anastomosis. Patients were followed up monthly for 1 year during which
      the patient's ability to urinate satisfactorily was assessed and any
      complications were noted. One hundred and forty-four (144) men, aged between 11
      and 76 years (mean 36.3 +/- 11.2 years), were studied. These included 121 cases
      who had rapidly recurring strictures after internal urethrotomy or dilatation and
      23 cases of complete stricture. Etiology of the stricture included external
      trauma (43.8%), postinflammatory (36.1%) and iatrogenic (post-catheterization;
      20.1%). Ninety-one (63.2%) strictures were in the anterior urethra, 47 (32.6%) in
      the posterior urethra and six (4.2%) bulbomembranous. The mean length of the
      strictures was 3.1 +/- 1.4 cm. RESULTS: Anastomotic urethroplasty was performed
      in 98 (68.1%) patients and substitution in 46 (31.9%). Hospital stay was between
      12 and 14 days, except in those who developed complications. Normal voiding was
      achieved in 124 (86.1%) patients. Urethral fistula was encountered in five (3.5%)
      patients and recurrent stricture in 15 (10.4%). There was no mortality.
      CONCLUSIONS: One-stage urethroplasty affords an excellent cost-effective means of
      reconstruction of the urethra in patients with stricture of various etiologies.
      In our environment in particular, it avoids the fulminating infection often
      encountered after the first stage of a two-staged operation.

PMID- 11442661
TI  - Apoptotic cell death and Smad4 expression in transitional cell carcinoma of the
      renal pelvis and ureter.
AB  - PURPOSE: To investigate the frequency of apoptosis and the expression of Smad4
      protein as well as their roles in transitional cell carcinoma (TCC) of the renal
      pelvis and ureter. METHODS: Apoptosis was detected by using terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)
      technique in 34 formalin-fixed and paraffin-embedded specimens of renal pelvic
      and ureteral TCC. The expression of Smad4 was immunohistochemically studied.
      RESULTS: The incidence of apoptosis ranged from 1.10 to 3.75% with a median of
      2.50% in TCC of the renal pelvis and ureter. The incidence of apoptosis was noted
      to be closely related to histologic grade but not to pathologic stage of the
      cancer. The expression of Smad4 was detected in six of 34 cases (17.6%).
      Regarding subcellular distribution, Smad4 protein was localized both in cytoplasm
      and nucleus of the cancer cells. In comparing the incidence of apoptosis with the
      expression of Smad4, no significant associations were seen between them. The
      expression of Smad4 was not related to the tumor grade nor stage of the cancer.
      CONCLUSIONS: The present study demonstrated close association of the incidence of
      apoptosis with the tumor grade of TCC of the renal pelvis and ureter.
      Significance of Smad4 expression was not noted in the study. It suggests that
      apoptotic cell death may play an important role in the tumor progression of renal
      pelvic and ureteral TCC.

PMID- 11442662
TI  - Retroperitoneoscopic ureterolithotomy for impacted ureteral stone.
AB  - Retroperitoneoscopic ureterolithotomy was successfully performed in two patients
      with impacted upper ureteral stone. The retroperitoneal space was extended using
      a balloon dissector and four ports were established into the retroperitoneal
      space according to Gaur's procedure (1993). The impacted ureteral stone was
      removed after the ureter was incised using a hook electrode. An indwelling splint
      or stent was placed in the ureter. The incised ureter was not sutured and an
      indwelling drain was placed in the retroperitoneal space. Urine leakage ceased
      within 3 days postoperatively. With regard to complications, the first patient
      developed wound infection caused by methicillin-resistant Staphylococcus aureus
      and the second patient had abscess formation in the psoas muscle.
      Retroperitoneoscopic ureterolithotomy should be useful as an alternative
      treatment for impacted ureteral stones because it involves minimal postoperative
      pain.

PMID- 11442663
TI  - Multiple endocrine neoplasia type 2B.
AB  - We report a case of multiple endocrine neoplasia type 2B (MEN 2B) in a 30-year
      old woman. There was no family history of MEN 2B in her family. DNA testing was
      carried out and a point mutation was found in exon 16, codon 918 (ATG to ACG) in
      the RET proto-oncogene. The woman died of medullary thyroid carcinoma, 13 years
      after a total thyroidectomy.

PMID- 11442664
TI  - Collecting duct carcinoma with long survival treated by partial nephrectomy.
AB  - A case is reported of collecting duct carcinoma of the left kidney treated with
      partial nephrectomy. A 57-year-old woman presented for evaluation of the left
      renal mass, which was detected by screening ultrasonography. A computed
      tomography scan and magnetic resonance imaging showed a solid mass at the upper
      pole of the left kidney. The renal tumor biopsy revealed a low-grade renal cell
      carcinoma or a tubulopapillary adenoma. Subsequently, left partial nephrectomy
      was performed. Microscopically, the tumor showed tubulopapillary proliferation
      with a fibrous capsule. Histochemically, the tumor cells reacted with lectins or
      antibodies against the collecting duct. Twenty-four months after partial
      nephrectomy, the patient is alive and has no distant metastatic lesions. We
      review the literature on collecting duct carcinoma, in addition to the case of
      partial nephrectomy.

PMID- 11442665
TI  - Synchronous occurrence of bladder carcinosarcoma and testicular seminoma.
AB  - We report a case of urinary bladder carcinosarcoma with simultaneous testicular
      seminoma. A 60-year-old male presented with painless gross hematuria and a left
      testicular mass. The bladder tumor was deeply infiltrating muscular tissue and
      had histologic features of both carcinoma and sarcoma. Testicular tumor was
      diagnosed as classical seminoma. Radical cystectomy, pelvic and left-modified
      retroperitoneal lymphadenectomy were performed. The lymph nodes did not show
      metastasis. At the 26 months follow-up, the patient is free of disease.

PMID- 11442666
TI  - Adenocarcinoma arising from the prostatic duct mimicking transitional cell
      carcinoma.
AB  - A 71-year-old man was first diagnosed with primary transitional cell carcinoma of
      the prostate with a skip lesion on the distal urethra. The patient received three
      courses of intra-arterial chemotherapy of cisplatin (CDDP) and pirarubicin (THP
      ADM) followed by a radical prostatectomy. Histopathologic examination of the
      prostatectomy specimen revealed adenocarcinoma invasion along the prostatic duct
      extending to the peripheral acini, which was diagnosed as ductal adenocarcinoma.
      The clinical and histopathologic features of this case are entirely different
      from usual adenocarcinomas of the prostate. This rare histopathologic feature
      should be recognized as 'ductal carcinoma of the prostate', to distinguish it
      from papillary adenocarcinoma or adenocarcinoma with endometrioid features. The
      patient has had no sign of recurrence 14 months after the operation. CDDP-based
      chemotherapy followed by radical prostatectomy may be one of the promising
      therapeutic modalities for this rare entity.

PMID- 11442667
TI  - Prostatic adenocarcinoma with marked neuroendocrine differentiation.
AB  - A case is presented of prostatic cancer with marked neuroendocrine
      differentiation. Double-labeled immunohistochemical staining was performed with
      prostate-specific antigen and Chromogranin A. Both antibodies were localized to
      some of the cancer cells with Paneth cell-like features. Furthermore, most of the
      cancer cells were positively stained with luminal cell marker CAM 5.2, suggesting
      that neuroendocrine cells originated from the prostatic luminal cells.

PMID- 11442668
TI  - Gene and immune therapy for renal cell carcinoma.
AB  - Conventional therapy for metastatic renal cell carcinoma is associated with a
      poor response rate and few patients are long-term survivors. The occurrence of
      spontaneous regression and the prolonged latency period between primary tumor
      removal and the appearance of metastases in some patients suggest the existence
      of important host immune responses to autologous tumor cells. With the advent of
      molecular gene transfer techniques and increased knowledge of the basic pathways
      of immune activation, the field of cancer immunotherapy has finally begun to
      develop novel and effective approaches for harnessing the immune system as a
      therapeutic agent. Current immunotherapy and gene therapy strategies, including
      methods of cytokine delivery and tumor-cell-based vaccines, are presented.

PMID- 11442669
TI  - Suicide gene therapy on LNCaP human prostate cancer cells.
AB  - The efficacy of combination suicide gene therapy was evaluated using a Herpes
      simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) system and an Escherichia
      coli cytosine deaminase/5-fluorocytosine (CD/5-FC) system on the LNCaP human
      prostate cancer cell model. Two types of plasmid vectors with the HSV-TK gene
      were constructed. A constitutive chicken beta-actin promoter drove one and a
      prostate-specific antigen (PSA) promoter drove the other. Similarly, a pair of
      plasmids with the CD gene under a cytomegalovirus (CMV) promoter and the PSA
      promoter was also constructed. LNCaP cells were transfected in vitro with either
      or both of those plasmids using a cationic lipid reagent. Transfected cells were
      treated with GCV and/or 5-FC. The percentage of viable LNCaP cells 7 days after
      treatment with HSV-TK/GCV or CD/5-FC under a constitutive promoter was 40% and
      41% of controls, respectively. The cell viability when two suicide genes were
      combined was 23%. The cell viabilities after four days with PSA promoter-HSV-TK
      vectors, CD vectors and a combination of both were 79%, 88% and 88%,
      respectively. Suicide gene therapy using either HSV-TK/GCV, CD/5-FC, or both, was
      effective in the LNCaP model. An additive effect was observed when the two
      suicide genes were used together. The PSA promoter did not seem to be effective
      enough to elicit cytotoxicity under the experimental conditions used here.

PMID- 11442670
TI  - Radical prostatectomy: making it a better operation in the new millennium.
AB  - Radical prostatectomy provides the best hope for long-term survival, free of
      disease, for organ-confined adenocarcinoma of the prostate. The operation is
      performed successfully only by understanding the remarkable anatomic variability
      of the prostate apex and the cylindrical nature of the striated urethral
      sphincter. When surgical techniques are used that take into account variations at
      the apex, with preservation of (i) neurovascular structures; (ii) the sphincteric
      urethra; and (iii) the adjacent levator ani, patients can look forward to a cure
      and the rapid return of urinary control and erectile function.

PMID- 11442671
TI  - Radical prostatectomy: time trends, morbidity and quality of life.
AB  - In recent years, increased screening for prostate cancer, primarily with prostate
      specific antigen testing, has led to an apparent increase in the incidence of
      prostate cancer and resulted in a shift to an earlier patient age and tumor stage
      at diagnosis. From the early 1980s, there have been great advances in surgical
      technique. In the 1990s, radical prostatectomy gained popularity among Japanese
      urologists. Time trends and morbidity of contemporary anatomical radical
      prostatectomy in Japan are reported here. In addition, the quality of life in men
      undergoing radical prostatectomy is discussed.

PMID- 11442672
TI  - Androgen deprivation in combination with radical prostatectomy for localized
      prostate cancer.
AB  - Radical prostatectomy is the only potential modality for cure in patients with
      localized prostate cancer. However, the lack of reliable and accurate clinical
      staging frequently leads to incomplete excision of tumor, with the consequences
      of early local recurrence or distant metastasis. Thus, the role of neoadjuvant or
      adjuvant hormonal treatment has been investigated in improving disease-free or
      cause-specific survival. This review reports the current status and problems of
      such androgen deprivation in combination with radical prostatectomy for localized
      prostate cancer.

PMID- 11442673
TI  - Brachytherapy for prostate cancer in Japan.
AB  - The temporary implantation of iridium-192 (Ir-192) is available in Japan if the
      patient is isolated in a radiation control area during the treatment. In this
      study, brachytherapy for prostate cancer was preceded by using low-dose rate Ir
      192. Twenty-six patients with localized prostate cancer were treated with
      brachytherapy since December 1997. The age of patients ranged from 61 to 82
      (median 76) years and the initial serum prostate-specific antigen (PSA) level
      ranged from 4.3 to 141 (median 17.4) ng/ml. Ten to 14 needles with Teflon sheaths
      were introduced into the prostate via a transperineal approach and an Ir-192 wire
      was placed in each sheath. The dose-distribution curve based on computed
      tomography imaging was drawn and the irradiation time was calculated for the
      whole prostate to receive over 70 Gy. During the 1-22-month follow-up period, all
      cases with an initial PSA level of less than 25 ng/ml showed continuous PSA
      decrease without biochemical failure. Magnetic resonance imaging demonstrated
      tumor regression in all cases within 6 months after the treatment. One-year
      biopsy specimens from patients with PSA failure demonstrated viable tumor cells,
      and the specimens from patients with favorable progress revealed fibrosis
      replacement without any variable tumor cells. Characterization of nocturnal
      penile tumescence data and IIEF 15 score proved the minimal effect of the
      treatment on erectile function. No major side effects or complications were
      observed. Brachytherapy using Ir-192 is a less invasive and safe procedure, which
      is expected to become a standard treatment for localized prostate cancer patients
      with relatively low PSA levels.

PMID- 11442674
TI  - Autocrine expression of neurotrophins and their receptors in prostate cancer.
AB  - Previously, it has been demonstrated that the neurotrophins and their receptors
      are present in human prostate tissue, but neither their functional role nor
      localization is clearly understood. We studied the expression of neurotrophins
      and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer
      specimens were obtained from patients undergoing radical prostatectomy, of whom
      25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The
      specimens were analyzed immunohistochemically for neurotrophins (nerve growth
      factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and
      their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed
      that both benign and malignant prostate gland epithelial cells expressed the
      neurotrophins and their receptors to various degrees, but no obvious
      immunopositive reaction was observed in stromal cells. In benign epithelial
      cells, the neurotrophins were localized to secretory cells and the receptors were
      localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a
      similar extent in prostate cancer specimens obtained from patients both with and
      without NHT. In contrast, the expression of TrkB was down-regulated and the
      expression of p75NTR was up-regulated in prostate cancer after hormonal therapy.
      These findings suggest that neurotrophins are secreted by prostate cancer cells
      in an autocrine fashion. Neurotrophins may be involved, through their receptors,
      in the escape mechanism from cell death after androgen depletion found in
      prostate cancer.

PMID- 11442675
TI  - Induction of apoptosis by cyclooxygenase-2 inhibitors in prostate cancer cell
      lines.
AB  - Prostaglandins are thought to play an important role in the proliferation of
      prostate cancer and are highly expressed in prostate cancer tissue.
      Cyclooxygenase-2 (COX-2), or prostaglandin endoperoxide synthase, is a key enzyme
      in the conversion of arachidonic acid into prostaglandin. In several cancers, COX
      2 contributes to the proliferation and metastasis of cancer cells. To assess the
      role of COX-2 in prostate cancer, we investigated whether the inhibition of COX-2
      affected the proliferation of prostate cancer cells. The human prostate cancer
      cell lines, LNCaP and PC 3, and a normal prostate stromal cell line (PrSC) were
      treated with COX-2 inhibitors NS 398 and Etodolac. The proliferation rate of the
      cell lines was examined using 3(4,5-dimethylethiazoly 1-2-) 2,5-diphonyl
      tetrazolium bromide (MTT) assays. A DNA fragmentation assay was also used for
      proof of apoptosis. COX-2 inhibitors could suppress the proliferation of LNCaP
      and PC 3 cells. In contrast, PrSC was not affected by COX-2 inhibitors. These
      suppressive effects occurred in a time- and dose-dependent manner. One of
      mechanisms responsible for cell death was apoptosis. COX-2 seems to play a
      significant role in the progression of prostate cancer. COX-2 may be a
      therapeutic target for prostate cancer. Since COX-2 inhibitors suppress
      proliferation and induce apoptosis in prostate cancer cells, and have no effect
      in normal prostate stromal cells, COX-2 inhibitors will be useful for the
      treatment of prostate cancer.

PMID- 11442677
TI  - The concept of care in male nurse work: an ontological hermeneutic study in acute
      hospitals.
AB  - AIMS: The aims of the study were to facilitate reflection upon an aspect of
      practice chosen by the participants, to explore and analyse these experiences and
      compare them with current literature on the concept of care in nursing practice.
      BACKGROUND: The concept of care is commonly used in the attempt to define what is
      unique about the role of the nurse, and both nursing and the concept of care are
      frequently associated with womanhood. Little research has been undertaken in
      relation to male nurse experiences and views on the concept. METHODS: The study
      used ontological hermeneutics to explore the concept of care in male nurse work
      in the acute general hospital setting. Eight male voluntary subjects from acute
      general hospital areas participated in the study and were asked to complete a
      summary of an experience from their practice that they felt exemplified care.
      Data for the study included the participants choice of practice experience, their
      subsequent reflections, the interview itself, the field journal and relevant
      literature and research. RESULTS: Six of the participants selected positive
      experiences in which they felt that their performance was satisfactory even
      though the events chosen for reflection were difficult and/or sad. The remaining
      two participants chose to reflect further on the difficulties they had within the
      experience. A conceptual model was constructed showing that the meeting of needs,
      effective communication and information giving were central to these nurses'
      explanations of care within their practice. All but two of the participants
      broadened their gaze to include the significant others of the patient.
      CONCLUSIONS: The reflections of these participants emphasize the emotional load
      of practice and a sensitivity on their part to the male stereotype of being able
      to cope with such pressures. It is suggested therefore that those providing and
      managing clinical supervision take into account the possible reluctance of male
      nurses to seek such support. Issues of gender should be emphasized in nurse
      education, as these nurses were sensitive to the impact of gender on their
      practice, both with patient/clients and their significant others, and with
      colleagues.

PMID- 11442678
TI  - The effects of unit morale and interpersonal relations on conflict in the nursing
      unit.
AB  - BACKGROUND: Health care organizations face major changes, and these changes are
      likely to increase conflict in organizations. Although numerous studies have
      focused on conflict management, few have considered causes and effect of conflict
      in nursing units. METHODS: The investigation tested a structural equation that
      examined the relationships among individual and contextual variables and
      intragroup conflict, job satisfaction, team performance effectiveness, and
      anticipated turnover. The nonrandom sample consisted of 141 nurses employed on 13
      inpatient units at a state-supported, 597-bed academic medical centre in a
      southeastern city. RESULTS: Intragroup conflict was higher on smaller units with
      a higher ratio of RNs to total staff. Intragroup conflict was not associated with
      satisfaction with pay or anticipated turnover. In the final model, the unit
      morale and interpersonal relations dimension of team performance effectiveness
      was negatively associated with intragroup conflict and anticipated turnover, and
      positively associated with satisfaction with pay. High perceptions of unit morale
      and interpersonal relations buffered the effect of unit size and skill mix on
      intragroup conflict. Goodness of fit statistics indicated a good fit of the model
      to data. CONCLUSION: The findings have implications for nursing educators and
      administrators, and provide direction for future research.

PMID- 11442679
TI  - From tall poppies to squashed weeds*: why don't nurses pull together more?
AB  - AIMS: To develop a conceptual framework to account for interpersonal conflict in
      nursing. To extend the boundaries of debate on the causes of interpersonal
      conflict in nursing. BACKGROUND/RATIONALE: In nursing, attempts to offer an
      explanation for staff conflict or, as it is traditionally referred to, horizontal
      violence, have, nearly always, been influenced by oppression and feminist
      theories. Such macrolevel analyses avoid discussing the details of individual
      acts of aggression in favour of considering nurses' alleged disempowerment in
      relation to other perceived dominant groups, especially male doctors, and the
      violence these groups inflict in terms of the denial of power, control, and
      access to rewards - material or otherwise. METHODOLOGY: A critical analysis of an
      extended literature review adapted from a doctoral dissertation. DISCUSSION:
      While the oppression and feminist perspectives can be insightful they are also
      limiting in that they omit the finer grained-analysis necessary for a fuller
      understanding of staff conflict. At least three levels of explanation can be
      offered to account for poor staff relationships - a macrolevel, which focuses on
      nurses' relationships vis-a-vis dominant groups, a mesolevel analysis, which
      concentrates on organizational structures, including workplace practices - many
      of which are controlled by nurses themselves, and a microlevel analysis, which
      emphasizes the interactional nature of interpersonal conflict. CONCLUSIONS: It is
      contented that it is not only the alleged misogyny intrinsic to oppression theory
      that shackles and impedes nurses, but nurses themselves, who in their everyday
      work and interpersonal interactions, act as insidious gatekeepers to an
      iniquitous status quo.

PMID- 11442680
TI  - A systems approach to the reduction of medication error on the hospital ward.
AB  - AIMS: To discuss a potentially powerful approach to safer medication
      administration on the hospital ward, based on principles of safety developed in
      other high-risk industries, and consistent with recent national reports on safety
      in health care released in the United Kingdom (UK) and United States of America
      (USA). To discuss why punitive approaches to safety on the hospital ward and in
      the nursing literature do not work. BACKGROUND: Drug administration error on the
      hospital ward is an ever-present problem and its occurrence is too frequent.
      Administering medication is probably the highest-risk task a nurse can perform,
      and accidents can lead to devastating consequences for the patient and for the
      nurse's career. Drug errors in nursing are often dealt with by unsystematic,
      punitive, and ineffective means, with little knowledge of the factors influencing
      error generation. Typically, individual nurses are simply blamed for their
      carelessness. By focusing on the individual, the complete set of contributing
      factors cannot be known. Instead, vain attempts will be made to change human
      behaviour - one of the most change-resistant aspects of any system. A punitive,
      person-centred approach therefore, severely hampers effective improvements in
      safety. By contrast, in other high-risk industries, such as aviation and nuclear
      power, the systems-centred approach to error reduction is routine. CONCLUSIONS:
      Accidents or errors are only the tip of the incident iceberg. Through effective,
      nonpunitive incident reporting, which includes reports of near-misses and system
      problems in addition to actual accidents, the systems-approach allows the
      complete set of contributing factors underlying an accident to be understood and
      addressed. Feedback to participants and targeted improvement in the workplace is
      also important to demonstrate that incident data are being used appropriately,
      and to maintain high levels of on-going reporting and enthusiasm for the scheme.
      Drug administration error is a serious problem, which warrants a well-reasoned
      approach to its improvement.

PMID- 11442681
TI  - Homeless children: the lives of a group of Brazilian street children.
AB  - AIM: To evaluate the life trajectories of a group of school-age street children
      frequenting two Sao Paulo city public shelters. BACKGROUND: A large proportion of
      the Brazilian child population suffers extreme disadvantage, although the
      Brazilian government gave the issue 'absolute priority' in 1990. Maternal and
      Under 5 mortality rates remain unacceptably high. In the metropolitan region of
      Sao Paulo an estimated 200 000 minors do not live with their mothers. Brazilian
      street children live lives of extreme personal and social risk. STUDY METHOD: The
      data were collected through individual, semi-structured interviews, with 14
      school age (7-12 years) participants frequenting two city public refuges, with
      their legal guardians' consent. Data analysis was based on Social Representation
      Theory and used content analysis. FINDINGS: The children's most meaningful
      experiences were grouped into the thematic categories of family, the street,
      friends, drugs, the police, the shelters and the future. Synthesis of these
      categories showed the lives of these children to be permeated by violence,
      resulting in experiences restricting their full development. CONCLUSION: The
      solution to their problems depends on pressure being put on the State by the
      civilian community in order to establish social and health policies that conform
      to the Child and Adolescent Statute (ECA). We consider that assisting street
      children involves attitudes that go beyond professional performance and demands
      acts of citizenship. RECOMMENDATIONS: The development of an ethical-political
      attitude by professionals to the problems of homeless street children is
      essential, and educational curricula should be appropriately constituted.
      Political projects to develop health and welfare policies and education should be
      directed to these children and their relatives, and include participation by
      health professionals to provide the necessary preventive and curative services.

PMID- 11442682
TI  - John Bowlby and James Robertson: theorists, scientists and crusaders for
      improvements in the care of children in hospital.
AB  - AIMS: John Bowlby and James Robertson, two men who were extremely influential in
      the latter part of the 20th Century, combined scientific theory with evangelism
      to bring about changes in the way in which children were cared for in hospitals
      and other institutions. This paper discusses their work together, their theories
      and their influence on the care of children and paediatric nursing. BACKGROUND:
      Bowlby and Robertson collaborated early in their working relationship on research
      about separation of mother and child. Bowlby was the scientist who developed
      classic theories about maternal separation. Robertson focused his research on
      separation of mother and child due to hospital admission. Between the two of
      them, they derived a classic theory about the phases of 'protest', 'despair' and
      'denial' (Bowlby called this last stage 'detachment') through which small
      children pass when isolated from their mothers for a length of time. DISCUSSION:
      Bowlby became an internationally recognized theorist, widely acclaimed and
      considered an expert in the field of maternal care and child development.
      Robertson, with his wife, Joyce, not only continued Bowlby's work investigating
      children separated from their mothers, but also took on the role of campaigner
      for the welfare of children in hospital. James Robertson, with his impressive
      speaking powers, established an international reputation proselytizing the need
      to admit parents to hospital with their children. The work of Bowlby and
      Robertson coincided with new knowledge about cross-infection, which had been one
      of the reasons for excluding parents from hospital wards. At the same time, and
      influenced by their work, community groups, which championed the idea of
      admitting parents with their children, developed. The combination of these
      factors provided a catalyst for changes within the health systems of many
      developed countries. Because of the theoretical work of Bowlby and Robertson's
      missionary zeal, government policies, staff attitudes and parents' expectations
      changed. Children's wards and hospitals in developed countries today admit
      parents as part of normal routine and actively involve them in the planning and
      implementation of their child's care.

PMID- 11442683
TI  - Nursing older dying patients: findings from an ethnographic study of death and
      dying in elderly care wards.
AB  - Nursing older dying patients: findings from an ethnographic study of death and
      dying in elderly care wards Background and aim. The aim of the study was to
      explore the experiences of dying patients and nurses working in three elderly
      care wards focusing on the management of care for dying patients. The majority of
      patients who die in hospital are over the age of 65 and evidence suggests that
      three fifths are over the age of 75. Older patients pose tremendous problems and
      challenges to nurses and doctors regarding the provision of good terminal care,
      particularly in relation to developing effective communication. METHOD: An
      ethnographic research design was chosen. The research sample consisted of 74
      patients, 29 nurses and 8 physicians. The principle data collection methods were
      participant observation and semi-structured interviews. All respondents were
      interviewed following a period of observation on each of the ward areas. The data
      obtained from participant observation were then used to structure the interview
      questions. The purpose of asking questions about meanings associated with
      observational material was to evaluate the extent to which convergence or
      divergence of the data was taking place. FINDINGS: The findings demonstrate that
      the care of older dying patients was defined by a lack of 'emotional engagement'
      with the patient and the institutionalized nondisclosure of information about
      death and dying. The study raises issues concerning the lack of effective
      communication about terminal diagnosis and the strategies used by nurses and
      doctors for disclosing information about death and dying. The findings suggest
      that although nurses provide individual care to dying patients, much of this was
      aimed at meeting patients' physical needs. Nurses reported psychosocial aspects
      including spiritual and emotional care to be important, although there was little
      evidence of them being orientated towards this in practice. CONCLUSION: The
      indicative conclusions from this study suggest that terminal care for some
      elderly patients remains hampered by a reluctance of nurses and doctors to be
      more open in their communication about death. It would appear that hospital
      culture and the mores, beliefs and ideologies that emanate from the biomedical
      model, significantly shape the experiences of older dying patients.

PMID- 11442684
TI  - Case studies of food shopping, cooking and eating habits in older women with
      Parkinson's disease.
AB  - AIMS: The principal aim of this study was to investigate how married and single
      living older women diagnosed with Parkinson's disease managed to shop for food,
      cook and carry out their meals; and to observe whether their nutritional needs
      were satisfied. A secondary aim was to identify women with severe motor problems
      and describe their food-related situation. BACKGROUND: Parkinson's disease is
      associated with motor and eating problems, which, combined with age-related
      declines in physical functioning, may affect activities of daily living and
      dietary intake. METHODS: Qualitative interviews and food survey were carried out
      in the homes of 10 women aged 67-80 years. The sample was recruited from
      outpatient registers. RESULTS: Decreased sense of smell, appetite and taste in
      combination with problems transporting food to the mouth and swallowing were
      risks for nutritional well-being. Food shopping was most difficult to manage, but
      six cooked even if their cooking style was changed. Married women with healthy
      husbands received support from their spouses. Single-living women suffering from
      motor problems had to call for help, which represented a threat to their well
      being. Independence was given high priority. CONCLUSIONS: The whole situation -
      including psychosocial and stress factors - must be taken into account when
      discussing shopping, cooking and eating among old women with Parkinson's disease.
      A home-helper should not take over but facilitate procedures so that the woman
      can manage as long as possible. This gave them self-esteem.

PMID- 11442685
TI  - Group reminiscence among people with end-stage chronic lung diseases.
AB  - BACKGROUND: Reminiscence is a process of recalling long-forgotten memorable
      experiences and events through verbal interaction between the person eliciting
      memories and one or more persons. Reminiscence is considered an effective
      treatment for various groups of people, particularly the elderly. AIM: This paper
      describes an intervention study on group reminiscence intervention for people
      with end-stage chronic lung diseases. The following hypotheses were proposed: (1)
      Depression in people with end-stage chronic lung diseases will decrease after
      participating in a reminiscence group. (2) Self-esteem in people with end-stage
      chronic lung diseases will increase after participating in a reminiscence group.
      (3) People with end-stage chronic lung diseases will report increased well-being
      after participating in a reminiscence group. METHODS: The research design was
      quasi-experimental, using Beck Depression Inventory and Rosenberg's Self-Esteem
      Survey pre- and posttreatment, in addition to conducting semistructured
      interviews after the treatment was finished and qualitatively evaluating outcomes
      of selected nursing diagnosis. A total of 12 patients participated, 10 women
      (mean age 70 years) and two men (mean age 86 years). The treatment was provided
      by two nurses to a group of patients dwelling at a long-term unit for people with
      end-stage lung diseases located in Iceland. A total of 13 group meetings were
      held, with 5-8 participants each time. Each group meeting had a preselected
      focus. It started with a short period of relaxation followed by a selected
      reading from a biography or from Icelandic literature and then the group
      discussion started, focusing on the topic of the day. RESULTS: The first two
      hypotheses were not supported. The following themes support the third hypothesis:
      (a) enjoyment, (b) feeling well and (c) closeness and affirmation of self and
      others. CONCLUSIONS: The purpose of the study was partly achieved. Although
      hypotheses one and two were not supported, the third was supported by the
      qualitative results, which clearly demonstrated that participation in the
      intervention increased well-being.

PMID- 11442686
TI  - Meeting the needs of consumers in the community: a working partnership in mental
      health in New Zealand.
AB  - AIM: The aim was to evaluate whether the services community mental health nurses
      provide are meeting the needs of consumers in the community. RATIONALE: The role
      of the mental health nurse in the community is changing as a result of
      deinstitutionalization, the consumer movement and the market model of health care
      delivery. In this context it is important for mental health nurses to evaluate
      whether the service they are currently providing is meeting the needs of
      consumers. DESIGN: This was a joint project between nurses and consumers. It was
      a service-specific descriptive research project utilizing qualitative methods of
      data collection and analysis that provides a model for working in partnership.
      FINDINGS: The results of this research identify collaboration in planning care
      and sharing information as two areas of concern but generally the consumers were
      very satisfied with the care provided by community mental health nurses. The
      analysis of the data suggests that consumers value nursing care because nurses
      provide support in their own home; they help consumers develop strategies for
      coping with their illness and their life; they provide practical assistance when
      it is required; they are vigilant about any deterioration or improvement; and
      they are available and accessible. CONCLUSION: The results of this study have
      demonstrated that nurses will remain critical to the success of community-based
      care because of their ability and willingness to be flexible to the demands of
      their own organization and the users of services.

PMID- 11442687
TI  - Risk factors associated with noncompliance with methadone substitution therapy
      (MST) and relapse among chronic opiate users in an Outer London community.
AB  - AIMS: The purpose of this study was to identify the risk factors associated with
      noncompliance with methadone substitution therapy (MST) and hence relapse in
      chronic opiate-dependent users, as this has major clinical implications
      especially in community-based detoxification programmes. BACKGROUND: Community
      mental health nurses (CMHNs) and other health/social care professionals need to
      be aware of the main risk factors associated with MST noncompliance among long
      term opiate users living within their catchment areas. The sex-matched patterns
      of biopsychosocial risk factors can be useful predictors of the ability of
      clients to comply with MST and their likelihood to complete the detoxification
      programme. A knowledge of the patterns of these high-risk factors also allows the
      care professionals to: (1) draw-up or re-draw care contracts that reflect their
      patients' biopsychosocial circumstances; (2) initiate much broader, client
      centred, relapse prevention strategies; (3) select suitable patients for
      specialized detoxification contracts; and (4) modify the care approach from
      detoxification to maintenance contracting particularly for clients with low
      predicted scores for the former contract-type. METHODS: As successfully
      demonstrated in this semi-quantitative descriptive investigation, identification
      of these sex-typed biopsychosocial high-risk factors can easily be undertaken
      during assessment and when the clients attend regular review. In this study,
      numerical information was gathered during personal face-to-face interviews, and
      was supplemented with that contained in past multidisciplinary case notes.
      RESULTS: Overall, the medication noncompliant female clients were associated with
      personality trait, decreased educational expectations, everyday life stresses,
      ambivalent thoughts, social company availability, comorbidity, boredom, and
      family-related conflicts; whereas the noncompliant male clients were associated
      with poor motivation, fashion and reputation, peer association, uncontrollable
      drug-cravings, drug availability, major life events, too stringent
      prescribing/poor client-centred care package, heavy intravenous users, young
      polydrug users, and triple users. CONCLUSIONS: These findings have important
      nursing practice connotations. This study is advocating the routine
      identification of biopsychosocial high-risk factors associated with MST
      noncompliance by all CMHNs working with chronic opiate-dependent users.

PMID- 11442688
TI  - Disclosure of minor mental health problems: an exploratory theoretical study.
AB  - AIM: The aim of this study was to explore people's experiences, concerns and
      beliefs about disclosing minor mental health problems by focusing on the ways in
      which such disclosures are interpreted. BACKGROUND: Approximately half of people
      with mental health problems do not seek help. The decision to consult represents
      just one aspect of the process of revealing one's illness to others. People with
      mental health problems are known to be reluctant to reveal the existence of those
      problems through fear of how others might then view them. DESIGN: A qualitative
      approach was employed. In-depth interviews were carried out with 47 users and
      nonusers of community mental health services. Interviews were tape-recorded,
      transcribed and analysed. RESULTS: The data suggest that when people reveal minor
      mental health problems others interpret these in relation to a number of
      perceived contextual factors. These include perceptions of the severity and
      duration of any possible causes, the inner 'strength' of the person, the expected
      ability of the person to either solve or suppress the experience, and the form
      and context of the expression itself. The data presented included individuals who
      were seeking help for relatively 'minor' mental health problems (primarily
      depression and anxiety) and individuals who had no current mental health problems
      but routinely managed expressions of their own emotions. Throughout the data
      there appeared to be no distinct difference between these two groups other than
      one of the severity of psychological experience. CONCLUSION: The key elements
      involved in the interpretation of people's expressions of sadness were
      essentially the same as those involved in the interpretation of expressions of
      depression. An appreciation of these contextual factors influencing the
      interpretation and disclosure of minor mental health problems may aid the
      development of more person-centred mental health services and inform the content
      of health education in the mental health field.

PMID- 11442689
TI  - Patients' perceptions of self-determination as expressed in the context of care.
AB  - AIM: The aim of this study was to describe patients' perceptions of how self
      determination finds expression in the context of care. BACKGROUND: Self
      determination is an important concept within health care as well as an important
      patient right. New legislation on patient rights in Sweden and Europe is aimed at
      increased patient self-determination. DESIGN AND METHOD: Data were collected
      through semi-structured, tape-recorded interviews with 17 strategically chosen
      patients within somatic care and analysed using a method inspired by
      phenomenography. RESULTS: The analysis found three descriptive categories of the
      informants' perceptions: trusting, accepting and a feeling of powerlessness. The
      patients expressed a great sense of trust and confidence in the care provided and
      they accepted the health care procedures. At the same time, they expressed a
      feeling of powerlessness because of not being part of decision-making, as well as
      lacking knowledge and information about treatment strategies. The patients wished
      to have the right of more self-determination but lacked the strength and
      knowledge to be able to influence their own care. CONCLUSIONS: Patients'
      perceptions of self-determination suggest that, in their encounters with the
      professional care, knowledge is expressed as power. The feeling of a lack of self
      determination can be reduced by help and support from a nurse who allocates time
      for communication in order to learn the patient's needs and reach a mutual
      understanding.

PMID- 11442690
TI  - Clinical decision making in nursing: theoretical perspectives and their relevance
      to practice.
AB  - AIM OF PAPER: This paper is a response to Thompson's paper 'A conceptual
      treadmill: the need for a middle ground in clinical decision making theory'
      published in the Journal of Advanced Nursing in 1999. SUMMARY OF CONTENT: This
      author agrees with his main recommendations, which are to seek a middle ground in
      the current polarized debate over clinical decision making in nursing, and to
      draw upon Hammond's Cognitive Continuum theory to do so. The theoretical
      background is sketched out, and the implications of these recommendations are
      analysed against this. It is argued that nurses now need to move the academic
      debate forward in such a way as to make serious impact on developing and
      improving practice. Cognitive continuum theory, in the way in which it focuses on
      practice, holds considerable potential to assist this move. CONCLUSION: Drawing
      on cognitive continuum theory necessarily leads to consequences which are not
      addressed in Thompson's paper: namely a need to consider the quality of nursing
      decisions, and a willingness to consider approaches to decision making which have
      been neglected or criticised by nurses. These consequences are explored here, and
      the implications of adopting this approach for nurses are outlined.

PMID- 11442694
TI  - The implications of contact with the mentor for preregistration nursing and
      midwifery students.
AB  - AIM OF THE PAPER: To examine the extent to which preregistration nursing and
      midwifery students have contact with their named mentor, and the implications of
      this. BACKGROUND/RATIONALE: Mentorship has an important part to play in enabling
      preregistration nursing and midwifery students to gain the maximum benefit from
      clinical placements. Previous research has indicated that the benefits of
      mentorship to learners are related to the number of occasions on which the
      student and mentor work together. DESIGN/METHODS: A research project commissioned
      by the Sheffield and North Trent College of Nursing and Midwifery (now the
      University of Sheffield School of Nursing and Midwifery) provided an opportunity
      to examine the extent to which their named mentors were available to Project 2000
      students, and the implications of this. Students and their named mentors were
      asked to keep an activity diary for 1 week. The main objective was to collect
      activity data to inform an analysis of the costs and benefits of clinical
      placements to service providers. This cost-benefit study has been published
      elsewhere. However, the data also cast light on the extent to which mentors were
      available to students, and the implications of this, and it is these findings
      which are presented here. RESULTS/FINDINGS: Students frequently worked shifts
      without their named mentors even though unrostered students often worked
      weekends, evening and night shifts in order to maximize time spent with their
      mentors. In the mentor's absence, other members of staff covered for some of
      their activities (in particular, direct and indirect supervision of students).
      However, students whose named mentors were absent spent significantly less time
      than other students working with a qualified member of staff as a partner in
      giving care. CONCLUSIONS: It is suggested that the extent to which named mentors
      are unavailable to Project 2000 students may be detrimental to the education and
      professional development of those students.

PMID- 11442695
TI  - Nursing students' perceptions of research: usefulness, implementation and
      training.
AB  - AIMS: The present study explored students' perceptions of the usefulness of
      research for nursing practice; beliefs about difficulties in implementing
      research on the wards; and finally, their satisfaction with the research training
      received. BACKGROUND: Anecdotal reports of nursing students' dislike of research.
      METHOD: Recruiting preregistration students for the present study was the first
      obstacle, and so the sample size remained small, consisting of 12 students. Semi
      structured interviews were conducted and later transcribed. RESULTS: The findings
      indicated that resistance, both by students and by qualified nurses, was a
      recurring issue. Several students disagreed with the training and expressed a
      need for more practical experience. CONCLUSIONS: Overall, the present study
      suggests that educational and organizational improvements need to be introduced
      to transform nursing into a research-active profession.

PMID- 11442696
TI  - Perceptions of labour pain by mothers and their attending midwives.
AB  - AIMS: The aim of the current study was to examine the perception of pain by
      labouring women and their attendant midwife, from the onset of labour to
      delivery. RATIONALE: Accurate measurement and appropriate management of pain is a
      significant problem for attendant medical and nursing personnel. Both the
      experience and perception of pain are regarded as subjective and are therefore
      difficult to measure objectively. Indeed, much of the literature reports that
      pain is often under- or over-estimated by nursing staff who as a consequence
      consistently fail to administer adequate analgesia. Few studies have specifically
      examined the ability of midwives to assess the pain of labouring women. DESIGN:
      The short form McGill Pain Questionnaire (SF-MPQ), routinely used to assess pain
      in obstetric environments, was used to determine pain perception. Thirteen
      labouring women and nine midwives completed the SF-MPQ every 15 minutes beginning
      at the time of admittance to the delivery suite. Peak pain ratings for the
      preceding 15 minutes were obtained without reference to prior ratings or each
      other's scores. Further, midwives in the maternity unit of The Queen Elizabeth
      Hospital (TQEH), Adelaide, South Australia completed a survey investigating the
      cues they use to assess pain during labour. RESULTS: On each measure of pain on
      the SF-MPQ, the midwives scores correlated with the mothers' scores across the
      entire pain range. Further analysis showed that mothers' and midwives' pain
      scores were similar at mild-moderate pain levels, but midwives significantly
      underestimated pain intensity at levels that mothers described as severe. The
      survey responses indicated that midwives rely on both verbal and nonverbal cues
      to assess pain levels. CONCLUSIONS: The cues used by midwives to differentiate
      pain intensities and qualities are similar to those used in other clinical
      settings, but may have limited discriminatory value as pain levels become severe.

PMID- 11442697
TI  - Constructions of sexuality for midlife women living with chronic illness.
AB  - AIM: In this paper, we reveal constructions of sexuality that were articulated by
      women who participated in an inquiry which aimed to understand the experiences of
      midlife women who live with chronic illness. The aim of this paper is to
      illuminate sexuality as an important health issue for women living with chronic
      illness and to offer ways that nurses may acknowledge and facilitate sexuality
      issues for women. BACKGROUND: The first author, as part of her doctoral study,
      corresponded with 81 women living with chronic illness. The participatory inquiry
      was framed by feminist principles and enabled women to anonymously share their
      experiences and collaborate in the direction of the research. During the analysis
      phase of the research, it became evident that illness had altered the way in
      which women conceptualized sexuality. DESIGN: The three authors performed
      secondary analysis of the original data set in order to re-examine the impact
      that chronic illness had on the sexuality of midlife women who live with chronic
      illness. Whilst we acknowledge that sexuality has multiple meanings, in this
      paper we describe the way in which women themselves have constructed and
      articulated their sexuality. FINDINGS: We found that sexuality incorporated
      women's desires, appearance, sexual feelings and expression and imposed on
      aspects of their lives that they had not needed to acknowledge before illness
      intruded. Three concerns are discussed; the changing body, meeting the needs of
      others and communicating sexuality. CONCLUSIONS: This paper reveals that issues
      of sexuality are an important health concern for women who live with long-term
      illness and should be acknowledged in sensitive and responsive health practices.
      The paper concludes that it is important for nurses to provide women opportunity
      for open and genuine communications about sexuality. In this way, a foundation of
      acceptance for the whole person is established which provides women permission to
      ask questions and seek assistance with sexuality issues.

PMID- 11442698
TI  - A study of practising nurses' perceptions and experiences of intimacy within the
      nurse-patient relationship.
AB  - AIM: This study investigated the perceptions and experiences of intimacy within
      the nurse-patient relationship. BACKGROUND: Intimacy is an increasingly
      recognized nursing concept, which is intrinsically related to the therapeutic
      potential of nursing. However, the nature of intimacy as practised in nursing
      remains largely unexplored. A qualitative design was used and a purposive sample
      of 10 nurses was involved. Data were collected by means of semistructured
      interviews and diaries. FINDINGS: Content analysis of the data yielded five
      categories relating to the nature of intimacy, involvement, resources, affinity
      for the patient and the rejection of intimacy. This paper focuses on the first of
      these categories. Intimacy emerged as a complex concept and included the
      subcategories of disclosure, levels of disclosure, sharing personal experiences,
      patient dependency and vulnerability, instrumental touch and intimacy and
      intimacy as an inappropriate term for the nurse-patient relationship. These
      findings are discussed in the light of existing theories and recommendations made
      for further research to expand and develop the issues highlighted. CONCLUSIONS:
      The paper concludes by highlighting the complexity of the concept and identifies
      some of the constraints to intimacy in practice such as insufficient resources,
      the health care system and role changes.

PMID- 11442699
TI  - Women's narratives during the acute phase of their myocardial infarction.
AB  - AIM: The purpose of this study was to illuminate the meaning of lived experiences
      during the acute phase of an acute myocardial infarction (AMI). METHOD: Ten women
      (< 60 years old) afflicted with AMI narrated their experiences during their stay
      in the coronary care unit (CCU). The interview texts were interpreted using a
      method with a phenomenological hermeneutic approach, inspired by the philosophy
      of Ricoeur. The text was divided into meaning units that were condensed and
      abstracted. Three themes were then extracted from the text. FINDINGS: One theme
      was 'oneself as vulnerable' with the subthemes: 'the feeling of being dependent
      upon others', 'the feeling of being insulted' and 'the feeling of being a
      troublesome person'. Another theme was 'oneself as distanced', with the
      subthemes: 'not facing the reality', 'captive in an unreal situation', and
      'inhibition out of concern for others'. The last theme was: 'oneself as making
      sense' with the subthemes: 'acquirement of some insight' and 'discovery of a new
      meaning with life'. CONCLUSION: The reported comprehensive understanding revealed
      the phenomena guilt and shame. These, in combination with the experience of being
      in an unreal situation and the withholding of feelings may have led to a
      deterioration of communication. It seems that relatives and the staff at CCU were
      not allowed to share the burden of being afflicted with an AMI.

PMID- 11442700
TI  - Going home from hospital: the carer/patient dyad.
AB  - AIMS: This study aimed to provide an in-depth understanding of the process of
      hospital discharge experienced by the carers of patients 'at risk' of
      unsuccessful discharge from medical wards in three hospitals in the North of
      England. BACKGROUND: The Community Care Act and the Carers Recognition and
      Services Act placed responsibility on service providers to ensure the smooth
      discharge of patients from hospital making sure that appropriate community
      services are in place to support the patient and their informal carer following
      discharge from hospital. The study, from which this paper is taken, identified
      patients at risk of unsuccessful discharge and tracked the experiences of the
      patient and their carer through the discharge process. For the purpose of the
      study unsuccessful discharge is defined as unplanned readmission within 6 weeks
      of discharge or extended length of stay. DESIGN: The study combined qualitative
      and quantitative methods to identify factors leading to unsuccessful discharge.
      Logistic regression was used retrospectively with the records of 1500 patients to
      identify factors predicting unsuccessful discharge. A sample of medical patients
      predicted to be at risk of unsuccessful discharge, their formal and informal
      carers, were followed through the discharge process using qualitative techniques
      to look at decision-making and outcomes related to discharge. FINDINGS: This
      paper presents findings relating to patient/carer experiences of the discharge
      process. It explores the obligate moral climate in which the role of carer is
      negotiated between professionals, patients, family members, friends and
      neighbours and the differing assumptions about duty associated with caring roles
      in hospital and in family and community settings. CONCLUSION: The discussion
      adopts a critical theory perspective to examine the contradictions confronting
      practitioners, patients and carers arising from hospital policies which promote
      cost-effective and efficient use of expensive technical resources while
      simultaneously seeking to identify and meet the needs of patients and carers for
      care.

PMID- 11442701
TI  - The quality of life for Hong Kong dialysis patients.
AB  - AIM: This study set out to measure the quality of life (QoL) of the dialysis
      patient. The first aim was to investigate the QoL of Hong Kong dialysis patients,
      and the second to understand the relationship between the demographic data and
      the QoL of the subjects. RATIONALE: Patients undergoing dialysis experience
      problems with disease-specific symptoms. The combination of a decrease in energy,
      the unavoidable emergence of socioeconomic problems, and emotional reactions
      compounds the stress facing the patient. The life of a dialysis patient may be
      lacking in quality. Few studies have examined the QoL of Hong Kong dialysis
      patients. More information is needed to establish how patients can be helped to
      lead more productive lives. METHODS: The Chinese Dialysis QoL Scale was used. A
      convenience sampling method was used to recruit patients from the outpatient
      clinics of dialysis centres. The distribution score on each item and the overall
      score were computed, with a lower score indicating greater negative impact of
      dialysis. To compare whether there is a difference in the average QoL score
      obtained between different groups on each of the demographic variables, one-way
      ANOVA followed by Tukey's post hoc analysis were used. Pearson's product moment
      correlation was used to examine the relationships between the demographic
      variables and the overall QoL score. FINDINGS: Of the 180 scales distributed, 164
      were returned, giving a response rate of 91%. The mean of the total score was
      132.5 with SD 16.68, varying between 97 and 179. The item mean score was 3.31.
      Marital status, type of modalities, and age appear to have no relationship to
      QoL. CONCLUSION: Patients undergoing dialysis in this study experienced multiple
      physical, social, economic and psychological changes. The priority of healthcare
      services should therefore be to provide support in the areas of family and social
      life, information and employment.

PMID- 11442702
TI  - Developing an evidence base for interdisciplinary learning: a systematic review.
AB  - AIM OF THE STUDY: The overall aim of the study was to explore the feasibility of
      introducing interdisciplinary education within undergraduate health professional
      programmes. This paper reports on the first stage of the study in which a
      systematic review was conducted to summarize the evidence for interdisciplinary
      education of undergraduate health professional students. METHODS: Systematic
      reviews integrate valid information providing a basis for rational decision
      making about health care which should be based on empirical and not anecdotal
      evidence. The accepted principles for systematic reviews were adapted in order to
      allow integration of the literature to produce recommendations for educational
      practice and guidelines for future research. FINDINGS: The literature on
      interdisciplinary education was found to be diverse, including relatively small
      amounts of research data and much larger amounts of evaluation literature.
      Methodological rating schemes were used to test for confounding influences in the
      research studies. The number of studies found was 141 but only 30 (21%) were
      included in the analysis because of lack of methodological rigour in the research
      and poorly developed outcome measures. CONCLUSIONS: Student health professionals
      were found to benefit from interdisciplinary education with outcome effects
      primarily relating to changes in knowledge, skills, attitudes and beliefs.
      Effects upon professional practice were not discernible and educational and
      psychological theories were rarely used to guide the development of the
      educational interventions.

PMID- 11442703
TI  - Methodologies analysing individual practice in health care: a systematic review.
AB  - AIM OF THE REVIEW: The aim of the systematic review was to identify, explore and
      evaluate the current level of knowledge of methodologies used in comparative
      analyses of the individual practice of doctors, nurses and midwives. RATIONALE:
      The question of how roles and responsibilities might be shared differently
      between professional groups in order to promote improved, cost-effective health
      care requires a systematic analysis of existing roles and practice. To do this
      effectively, knowledge of the methodologies available for such an analysis is
      essential. METHODS: A systematic review of the literature published since 1989
      comparing the practice of doctors, nurses and midwives was undertaken. FINDINGS:
      The findings are presented in tabular format and include the following categories
      of published methodologies: experimental/quasi-experimental;
      descriptive/nonexperimental and qualitative studies. The discussion centres on a
      critique of quantitative methodologies used to analyse individual practice in
      relation to role substitution and diversification. The potential contribution of
      qualitative methodologies in the analysis of individual practice is discussed.
      CONCLUSIONS: The authors conclude that the current level of knowledge is biased
      towards quantitative research. It is argued that the assessment of health care
      roles and responsibilities would be well served by a more balanced approach that
      recognizes the strengths of both quantitative and qualitative work.

PMID- 11442704
TI  - Continuous video recording: a new clinical research tool for studying the nursing
      care of cancer patients.
AB  - AIM: The aim of this study was to clarify issues around the patient-nurse
      interaction during pulsed dose rate (PDR) brachytherapy. BACKGROUND: Cancer
      diagnosis, response and survival rates as well as the side-effects of radiation
      therapy are well described in international literature. However, no scientific
      data apparently exist on the reactions and behaviour of cancer patients during
      stressful irradiation treatments nor on nursing performance in these situations.
      The study involved gynaecological and anal cancer patients. Treatment needles (10
      20 cm) were implanted in the tumours of these patients during the PDR
      brachytherapy. This treatment was administered during a 15-30-minute period each
      hour, for a duration of 30-60 hours. Patients were partially isolated and
      immobilized, and typically positioned on the back or side. In preparation for the
      therapy, patients had to fast and drink sparingly. Observation and nursing care
      could only be performed during pauses in the treatment. METHOD: This paper is
      based on 142 hours of continuous video recording of patients undergoing PDR
      brachytherapy. Data were collected on five patients and 17 nurses. FINDINGS: The
      study shows that nurses were with patients for approximately 1/4 of the available
      time. The majority (75%) of any communication with patients centred around
      physical care. Although patients were in a stressful situation, they did not
      anticipate receiving any psychological support from nursing staff. Patients
      showed individual patterns of behaviour and coping. CONCLUSIONS: Continuous video
      recording, as a research tool can document accurately interaction and behaviour
      between cancer patients and nursing staff. Video recording discloses examples of
      both eminent and negligent nursing care and as such can be a useful tool for
      instruction and for future research. The credibility, validity and limitations of
      using video recording are discussed.

PMID- 11442705
TI  - Improvements in the quality of co-ordination of nursing care following
      implementation of the Resident Assessment Instrument in Dutch nursing homes.
AB  - AIM: To study the effect of implementation of the Resident Assessment Instrument
      (RAI) on the quality of co-ordination of nursing care in Dutch nursing homes.
      BACKGROUND: The Resident Assessment Instrument (RAI) was designed to improve the
      quality of care and quality of life in nursing homes. Until now, only
      noncontrolled studies on the effects of implementation of the RAI have been
      carried out. DESIGN/METHODS: Quasi-experimental; intervention wards with RAI
      compared with wards with no intervention. We used the co-ordination of nursing
      care instrument, which includes measures for case history, care plan, end of
      shift report, communication, patient allocation and patient report. The scores on
      these scales represent the quality of nursing procedures on a ward. The
      measurements were done 1 month before and 8 months after RAI-implementation in 18
      wards in 10 nursing homes in the Netherlands. RESULTS: Out of 348 somatic
      patients on the participating wards who met the inclusion criteria and signed an
      informed consent, 278 could be measured at the first and 218 at the second data
      collection. 175 residents could participate twice. We used a meta-analysis
      technique to study the mean differences between eight couples of RAI/control
      wards before and after the intervention. The mean difference scores showed
      significant positive improvement in the RAI group for case history, there were
      minor (not statistically significant) improvements for all other scores and the
      total score. These results are encouraging especially in light of the fact that
      RAI-implementation in all the experimental wards did not proceed according to
      plan, owing to staffing and software problems. CONCLUSIONS: We conclude that the
      RAI has the potential to improve the quality of co-ordination of care in nursing
      homes.

PMID- 11442706
TI  - The team survey: a tool for health care team development.
AB  - AIMS: The aim of this study was to validate a psychometric tool, the team survey,
      in a health care setting with a range of teams from a Large National Health
      Service (NHS) Trust. BACKGROUND: The team survey was developed by Millward and
      Ramsay (1998) to measure the team dimensions identified in the cognitive
      motivational model of team effectiveness (Millward & Purvis 1998). The team
      dimensions are team potency, team identification, Shared Mental Models and team
      meta-cognitions. DESIGN AND METHODS: The psychometric properties of the tool as a
      reliable and valid predictor of team effectiveness was assessed by way of a
      survey of 10 teams (comprising 124 members in all) located on different premises,
      within a large NHS Trust. Team size ranged between 5 and 19 members, with average
      team size being 10 members. Two independent ratings of 'effectiveness' were made
      for each team. Factor and multiple regression analyses were employed to identify
      the most powerful predictors of health care team effectiveness from a cognitive
      and motivational perspective. RESULTS: The results suggest that the team survey
      is psychometrically robust within a health care setting. CONCLUSIONS: It is
      concluded that the tool has a potentially key role in informing and evaluating
      team development initiatives in support of the work of practice development
      nurses and nursing team leaders.

PMID- 11442707
TI  - Methodological issues in interviewing families in family nursing research.
AB  - AIM OF THE STUDY: The aim of this study is to discuss what methodological
      problems can be met in family research with one family member as an interviewee
      speaking on behalf of the whole family and, vice versa, what is the meaning of
      having multiple family members or the whole family unit as informants.
      BACKGROUND: Family nursing research is part of multidisciplinary research with
      families. It is a basis for family nursing and contributes to research,
      especially from the perspective of family welfare and its promotion. Family
      nursing research generates knowledge concerning families' and family members'
      wellbeing and experiences and expectations of nursing and health care. METHODS:
      The examination of methodological problems while pursuing family research is
      based on two studies conducted in Finland. FINDINGS: Quantitative methods add to
      the general knowledge of families. Qualitative methods are well suited to the
      study of family experiences. Family interviews performed for research purposes
      differ from interviews aiming at caring for families. They aim at obtaining
      knowledge of families on a general level so as to improve family nursing. Family
      research has to be looked at as a whole. It faces many challenges such as the
      definition of the family, gaining access, methods of data collection and data
      management. CONCLUSIONS: A family is a complex system and research with families
      need flexible, sensitive and practical methods. Family research should also aim
      at developing new methods for data collection and analysis.

PMID- 11442708
TI  - The quality of perioperative care: development of a tool for the perceptions of
      patients.
AB  - AIM OF THE STUDY: To find out how surgical hospital patients (n=874) perceived
      the quality of perioperative care they received in an operating department and in
      the recovery room. BACKGROUND: Patients' perceptions of the perioperative care
      have not been included systematically in the improvement of the care.
      Accordingly, there is no standardized, valid, and reliable instrument or system
      in common use that we could use for the evaluation. The nursing care in operating
      departments has an important role in modern health care, and therefore more
      research concerning perioperative care quality is needed urgently and the
      development of the measurement tool is urgent. METHOD: The data were collected
      using a structured questionnaire in five operating departments in southern
      Finland during 1998. RESULTS: Physical activities (such as pain management and
      temperature maintenance) were rated as excellent, as were staff characteristics
      and the physical and social environment. The most critical comments were made
      with regard to supporting patient initiative, encouragement and educational
      activities. Patients stated they would have liked more information and it was
      felt that they should have been encouraged to ask more questions about unclear
      matters. Some of the patients said they had only very limited influence over
      their own care. The patients were very pleased with their care in the recovery
      room. There were only minor differences between the views of patients from
      different departments. CONCLUSIONS: Overall the quality of care was considered
      extremely good, but comparisons of different quality categories did reveal some
      problems. Although it has already proved to be a useful tool, the questionnaire
      needs to be developed and tested further.

PMID- 11442709
TI  - Spread and prevention of some common viral infections in community facilities and
      domestic homes.

PMID- 11442710
TI  - The influence of packaging methodology on the microbiological and fatty acid
      profiles of refrigerated African catfish fillets.
AB  - AIMS: The shelf-life of refrigerated catfish fillets was determined at 2 degrees
      C, to simulate retail conditions, using two types of packaging materials, vacuum
      packing (VP) and oxygen permeable packaging (OPP). METHODS AND RESULTS:
      Representative samples (n=5) from both types of packaging methods were drawn at
      random every 2 d until a microbiological count of 106 cfu g-1 was reached.
      Samples were pooled and screened microbiologically using standard methods. Fatty
      acid analyses of total lipids, neutral lipid, glycolipid and phospholipid
      fractions were also conducted, to determine at which point the fish was regarded
      as spoiled and which packaging method provided a longer shelf-life. OPP limits
      storage to a maximum of 4 d (aerobic plate count of 8.2 x 105 cfu g-1), whereas
      VP extends the shelf-life of the fillets to between 6 and 8 d (aerobic plate
      count of 9.2 x 104 cfu g-1 and 1.66 x 106 cfu g-1, respectively). Similarly,
      coliform counts increased with time; however, packaging material had no
      statistical influence thereon. CONCLUSION: Until d 13, when the experiment was
      terminated, no deterioration in lipid composition of the various fractions was
      noted. SIGNIFICANCE AND IMPACT OF THE STUDY: An extended shelf-life
      microbiologically-speaking, for potential processors, could thus be obtained by
      using VP instead of OPP.

PMID- 11442711
TI  - Real-time PCR used to measure stress-induced changes in the expression of the
      genes of the alginate pathway of Pseudomonas aeruginosa.
AB  - AIMS: To measure the concentration of mRNAs transcribed from four genes involved
      in alginate production using real-time PCR. METHODS AND RESULTS: The mRNA
      concentrations in cells grown in normal and stress conditions were compared. A
      difference in the expression of algD, the key gene leading to overproduction of
      alginate, was detected between alginate-producing and non-alginate-producing
      strains grown under normal conditions. After growth on 3% ethanol (known to
      stimulate alginate production), but not after heat-shock, an increase in algD
      mRNA levels and a corresponding decrease in mucB (a regulatory gene) mRNA levels
      were detected in all strains. CONCLUSION: The quantitative results suggest that
      the mucB gene may have a role in recognition of stress conditions, and that
      having a disrupted mucA gene does not always result in a mucoid phenotype.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Real-time PCR can be used to quantify mRNA
      and is a convenient method of analysing bacterial gene expression.

PMID- 11442712
TI  - Enumeration of Campylobacter in New Zealand recreational and drinking waters.
AB  - AIMS: To use a published polymerase chain reaction (PCR) method for the detection
      and identification of thermotolerant Campylobacter species (Camp. jejuni, Camp.
      coli and Camp. lari) in tandem with a Most Probable Number (MPN) technique to
      enumerate these species in water samples. METHODS AND RESULTS: An initial study
      of 42 river water samples compared the use of conventional culture and PCR
      methods for the detection of Campylobacter in MPN enrichment tubes. It was found
      that all samples positive by culture were also positive by PCR. Thirty-seven
      percent more MPN tubes were positive by PCR compared with culture. The MPN/PCR
      technique was subsequently applied to 96 additional samples collected from
      rivers, drinking, roof and shallow ground water. Campylobacter was especially
      prevalent in river water (60% positive) and shallow ground water (75% positive)
      samples. Drinking water (29.2% positive) and roof water (37.5% positive) also
      contained Campylobacter, but the numbers detected were very low (maximum 0.3 and
      0.56 MPN 100 ml-1, respectively). CONCLUSION: River waters contained
      Campylobacter at higher levels than any other water type and in a high percentage
      of the samples. Although Campylobacter was present in treated drinking water, the
      levels detected were low. SIGNIFICANCE AND IMPACT OF THE STUDY: These results
      suggest that water may act as a significant transmission route for human
      campylobacteriosis.

PMID- 11442713
TI  - The effects of surface roughness and type of denture acrylic on biofilm formation
      by Streptococcus oralis in a constant depth film fermentor.
AB  - AIMS: To investigate the effects of surface roughness and type of denture acrylic
      on the early development of a Streptococcus oralis biofilm in a constant depth
      film fermentor (CDFF). METHODS AND RESULTS: Streptococcus oralis was incubated
      with acrylic of known surface roughness in the CDFF. Adherent Strep. oralis were
      enumerated by viable counting. Cold-cure acrylic was rougher (P < 0.01) than heat
      cure acrylic after polishing with abrasive paper of any given grit-grade. Heat
      cure acrylic was colonized by fewer (P < 0.001) bacteria than cold-cure acrylic
      at any given surface roughness. The number of bacteria adhering to heat-cure and
      cold-cure acrylic increased linearly with mean surface roughness after 2 h
      incubation, the increase being greater (P < 0.001) for the cold-cure compared
      with the heat-cure acrylic. However, after 4 h incubation, surface roughness
      appeared to have no effect on the number of adherent bacteria. CONCLUSION: The
      type of acrylic used, and its roughness, affect the early stages of biofilm
      formation by Strep. oralis. SIGNIFICANCE AND IMPACT OF THE STUDY: Choosing an
      appropriate type of smooth acrylic could lead to reduced biofilm formation in
      vivo.

PMID- 11442714
TI  - Population dynamics and antagonistic potential of enterococci colonizing the
      phyllosphere of grasses.
AB  - AIMS: To investigate the spatial and temporal dynamics of enterococci colonizing
      forage grass and their ability to produce bacteriocins. METHODS AND RESULTS:
      Enterococci could be detected on above-ground plant parts throughout the growing
      season, with high continuity but low cell numbers (2.60 x 101-6.16 x 104 cfu g-1
      fresh matter). A total of 750 strains were isolated and identified by their whole
      cell protein patterns as Enterococcus faecalis (7.9%), Ent. mundtii (7.9%), Ent.
      casseliflavus (5.5%), Ent. faecium (5.2%) and Ent. sulfureus (0.1%). The vast
      majority of the strains (69.7%) formed a homogeneous 16S rDNA genotype that
      differed from those of known enterococci. A screening for antagonistic activity
      using an agar spot test revealed that 18.4% of all isolates were potential
      antagonists. Partially-purified proteins extracted from cell-free culture
      supernatant fluids of various species were characterized as pH- and heat-stable
      bacteriocins active against a wide range of lactic acid bacteria, clostridia and
      Listeria. The producing strains were antagonistically active even on 'phylloplane
      agar' at temperatures between 4 and 37 degrees C. CONCLUSION: Enterococci are a
      common part of the epiphytic microflora of grasses, displaying probably some
      antagonistic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The results provide
      new information on the distribution, species diversity and antagonistic potential
      of enterococci in the phyllosphere.

PMID- 11442715
TI  - The role of non-Saccharomyces species in releasing glycosidic bound fraction of
      grape aroma components--a preliminary study.
AB  - AIMS: The purpose of the study was to evaluate the effect of beta-glycosidase
      activity in wine yeasts in releasing terpene glycosides from grape juice. METHODS
      AND RESULTS: Glycosidase activity was screened in 160 yeasts by testing their
      ability to hydrolyse arbutine on agar plates. Only non-Saccharomyces species
      exhibited beta-glycosidase activity. Enzyme activity, based on hydrolytic
      activity on p-nitrophenyl-beta-glycoside, was mainly located in the whole cell
      fraction, with smaller amounts in permeabilized cells being released into the
      growth medium. The hydrolysis of glycosides was determined by HRGC-MS, confirming
      the role of yeast in the liberation of monoterpenols, especially linalool and
      geraniol. CONCLUSION: The results indicate the potential of microbial beta
      glycosidases for releasing flavour compounds from glycosidically-bound, non
      volatile precursors, with significant implications for wines made from less
      aromatic grapes. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms the
      role of non-Saccharomyces species in enhancing wine aroma and flavour, suggesting
      that the future lies with controlled use of mixed cultures in winemaking.

PMID- 11442716
TI  - Analysis of Salmonella enteritidis strains isolated from food-poisoning cases in
      Taiwan by pulsed field gel electrophoresis, plasmid profile and phage typing.
AB  - AIMS: To establish the molecular typing data for Salmonella enteritidis due to
      its increasing role in Salmonella infections in Taiwan. METHODS AND RESULTS:
      Sixty-three Salm. enteritidis strains isolated from related and unrelated
      patients suffering from food-borne poisoning during 1991-97 were collected and
      subjected to pulsed field gel electrophoresis (PFGE), plasmid analysis and phage
      typing. For PFGE, XbaI, SpeI and NotI restriction enzymes were used for
      chromosomal DNA digestion. The results showed that, for these 63 Salmonella
      strains, 10 PFGE pattern combinations were found. Of these, pattern X3 S3 N3 was
      the major subtype, since 46 strains isolated from different locations at
      different times during 1991-97 showed this PFGE pattern. Plasmid analysis showed
      only three plasmid profiles and phage typing showed that most of the Salmonella
      strains were of the phage type PT4. CONCLUSION: Most of the Salm. enteritidis
      strains circulating in Taiwan are of very similar genetic types or are highly
      related and that strains of PFGE pattern X3 S3 N3 are the prevalent and
      recirculating strains of Salm. enteritidis which caused food-poisoning cases in
      Taiwan in 1991-97. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides
      information that in Salmonella infection, certain subtypes of Salm. enteritidis
      should be scrutinized.

PMID- 11442717
TI  - Possible mechanisms for the relative efficacies of ortho-phthalaldehyde and
      glutaraldehyde against glutaraldehyde-resistant Mycobacterium chelonae.
AB  - AIMS: This investigation compared glutaraldehyde (GTA)-sensitive and -resistant
      strains of Mycobacterium chelonae and examined the effects of pretreatment of GTA
      sensitive and -resistant strains of Myco. chelonae with chemical agents that
      interfere with cell wall synthesis. METHODS AND RESULTS: When exposed to 2% (v/v)
      GTA at 25 degrees C, GTA-resistant strains of Myco. chelonae dried on to glass
      carriers were not inactivated to any significant extent. By contrast, GTA
      sensitive strains of Myco. chelonae and a strain of Myco. terrae suffered a > 6
      log reduction in viability in 5 min. However, ortho-phthalaldehyde (OPA; 0.5%
      w/v) achieved a corresponding inactivation against two GTA-resistant strains
      within 5-10 and 10-20 min, respectively. Electron microscopy, using a non
      aldehyde fixation process and also negative staining, failed to detect any
      extensive changes in GTA-sensitive and -resistant cultures exposed to GTA or OPA.
      Thin-layer chromatography was unsuccessful in detecting differences between GTA
      resistant and -sensitive strains of Myco. chelonae. However, pretreatment of GTA
      resistant cells with mycobacterial cell wall synthesis inhibitors increased their
      subsequent susceptibility further to OPA but not to GTA. CONCLUSION: Ortho
      phthalaldehyde is an effective new biocidal agent that, at its in-use
      concentration, is rapidly bactericidal to non-sporulating bacteria, including GTA
      sensitive and -resistant mycobacteria. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Pretreatment of GTA-resistant cells with mycobacterial cell wall synthesis
      inhibitors increased their subsequent susceptibility to OPA but not to GTA.

PMID- 11442718
TI  - A study of the effect of isothiazolones on the performance and characteristics of
      a laboratory-scale rotating biological contactor.
AB  - AIMS: To study the effect of the isothiazolone biocide (Kathon WT) on the
      performance of laboratory-scale rotating biological contactors (RBCs) and their
      component biofilms. METHODS AND RESULTS: Biofilms were established on the RBCs
      and then exposed to 0.7-15 p.p.m. isothiazolones. Young, 1-week-old, biofilms
      were found to attain treatment efficiency equal to that of mature, 2-month-old,
      biofilms. Isothiazolone concentrations at 3 p.p.m. and above caused a progressive
      decline in treatment efficiency and 15 p.p.m. isothiazolones inhibited all
      microbial activity and resulted in the death of the biofilms. Bio-oxidation and
      the biodegradation of isothiazolones within the biofilms ontinued unhindered at
      concentrations which caused the total inhibition of planktonic bacteria.
      CONCLUSION: There was at least a 10-fold difference in susceptibility of
      planktonic and biofilm bacteria to isothiazolones. The chemical oxygen demand
      (COD) test was shown to be a reliable tool for investigating the efficiency of
      wastewater treatment units when the influent contains isothiazolones, while the
      biochemical oxygen demand (BOD) was unreliable due to the inhibition of bio
      oxidation by the biocide. SIGNIFICANCE AND IMPACT OF THE STUDY: The results show
      that RBCs can be used to treat effluents containing isothiazolones at
      concentrations up to 1.5 p.p.m.

PMID- 11442719
TI  - Surface hygiene monitored using a reporter of fis in Escherichia coli.
AB  - AIMS: To examine the value of the fis promoter in monitoring regrowth of a
      surface-attached bacterial population following exposure to chemical stress using
      several candidate reporters, beta-galactosidase (lacZYA), bacterial luciferase
      (luxAB) and enhanced green fluorescent protein (EGFP). METHODS AND RESULTS: The
      pattern of expression for the reporters within Escherichia coli cells attached to
      surfaces was determined. Both the bacterial luciferase reporter and EGFP were
      readily detected, but EGFP was found to overcome problems associated with
      luciferase and beta-galactosidase. The effect of surface pretreatment, using
      polymer systems, on bacterial attachment and growth confirmed the usefulness of
      this approach. CONCLUSION: The fis promoter, combined with EGFP, can be used
      successfully to study adhesion, biocidal damage and recovery. The stability of
      the EGFP enabled the magnitude of the total recovery response to be monitored as
      cells remained fluorescent after the decline in fis expression. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The E. coli Pfis-egfp reporter system provides a new,
      versatile and sensitive tool to investigate bacterial adhesion both
      quantitatively and qualitatively.

PMID- 11442720
TI  - A repeatable laboratory method for testing the efficacy of biocides against
      toilet bowl biofilms.
AB  - AIMS: The purpose of this study was to develop a laboratory biofilm growth
      reactor system that simulated the toilet bowl environment and which could be used
      for biocide efficacy testing. METHODS AND RESULTS: A microbial biofilm reactor
      system incorporating intermittent flow and nutrient provision was designed. The
      reactor system was open to the air and was inoculated with organisms collected
      from toilet bowl biofilms. Once per hour, reactors were supplied with a nutrient
      solution for a period of 5 min, then flushed and refilled with tap water or tap
      water amended with chlorine. Quantitative measures of the rate and extent of
      biofilm accumulation were defined. Biofilm accumulated in untreated reactors to
      cell densities of 108 cfu cm-2 after approximately 1 week. Biofilm accumulation
      was also observed in reactors in the continuous presence of several milligrams
      per litre of free chlorine. Repeatability standard deviations for the selected
      efficacy measures were low, indicating high repeatability between experiments.
      Log reduction values of viable cell numbers were within ranges observed with
      standard suspension and hard surface disinfection tests. Biofilm accumulated in
      laboratory reactors approximately seven times faster than it did in actual toilet
      bowls. The same ranking was achieved in tests between laboratory biofilms and
      field-grown biofilms with three of the four measures, using three different
      concentrations of chlorine. CONCLUSION: This reactor system has been shown to
      simulate, in a repeatable way, the accumulation of bacterial biofilm that occurs
      in toilet bowls. The results demonstrate that this system can provide repeatable
      assays of the efficacy of chlorine against those biofilms. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The laboratory biofilm reactor system described herein can
      be used to evaluate potential antimicrobial and antifouling treatments for
      control of biofilm formation in toilet bowls.

PMID- 11442721
TI  - An integrated method for the enrichment and selective isolation of
      Actinokineospora spp. in soil and plant litter.
AB  - AIMS: To devise and evaluate a method for isolating the rare, zoosporic
      actinomycetes, Actinokineospora spp. in soil and plant litter. METHODS AND
      RESULTS: The newly developed method consists of two enrichment stages followed by
      plating on a selective medium. The source material is initially incubated with
      calcium carbonate to multiply the population of Actinokineospora spp., and is
      then air-dried. The second stage consists of rehydration-centrifugation, in which
      the amended substrate is immersed in phosphate buffer-soil extract to liberate
      actinomycete zoospores, and nonmotile microbial associates are then eliminated by
      centrifugation. Portions of the supernatant enriched with zoospores are plated on
      humic-acid vitamin agar supplemented with fradiomycin, kanamycin, nalidixic acid
      and trimethoprim. We examined 39 soil and plant-litter samples taken from fields,
      forests and stream banks. The proposed method consistently enriched and
      selectively isolated Actinokineospora spp. in 17 samples. Evidence for
      antimicrobial activity was found in most of the isolates. CONCLUSION: A
      combination of enrichment and a medium containing selective antibiotics can be
      used successfully for efficient isolation of certain rare actinomycete taxa.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The development of new methodologies with
      which to isolate rare actinomycetes is of great importance to extend our
      understanding of their ecology, taxonomy and bioactivity.

PMID- 11442722
TI  - An analysis of bacteriocins produced by lactic acid bacteria isolated from malted
      barley.
AB  - AIMS: The aim of this study was to perform a detailed characterization of
      bacteriocins produced by lactic acid bacteria (LAB) isolated from malted barley.
      METHODS AND RESULTS: Bacteriocin activities produced by eight LAB, isolated from
      various types of malted barley, were purified to homogeneity by ammonium sulphate
      precipitation, cation exchange, hydrophobic interaction and reverse-phase liquid
      chromatography. Molecular mass analysis and N-terminal amino acid sequencing of
      the purified bacteriocins showed that four non-identical Lactobacillus sakei
      strains produced sakacin P, while four Leuconostoc mesenteroides strains were
      shown to produce bacteriocins highly similar or identical to leucocin A, leucocin
      C or mesenterocin Y105. Two of these bacteriocin-producing strains, Lb. sakei 5
      and Leuc. mesenteroides 6, were shown to produce more than one bacteriocin.
      Lactobacillus sakei 5 produced sakacin P as well as two novel bacteriocins, which
      were termed sakacin 5X and sakacin 5T. The inhibitory spectrum of each purified
      bacteriocin was analysed and demonstrated that sakacin 5X was capable of
      inhibiting the widest range of beer spoilage organisms. CONCLUSION: All
      bacteriocins purified in this study were class II bacteriocins. Two of the
      bacteriocins have not been described previously in the literature while the
      remaining purified bacteriocins have been isolated from environments other than
      malted barley. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents a
      thorough analysis of bacteriocin-producing LAB from malt and demonstrates, for
      the first time, the variety of previously identified and novel inhibitory
      peptides produced by isolates from this environment. It also highlights the
      potential of these LAB cultures to be used as biological controlling agents in
      the brewing industry.

PMID- 11442723
TI  - A novel in vitro model system to grow films of oral bacteria for the study of
      human tooth root surface caries.
AB  - AIMS: To develop a simple and flexible novel in vitro model system to grow films
      of oral bacteria that could be used to study aspects of dental caries. METHODS
      AND RESULTS: Standardized suspensions of bacteria were inoculated into Ultrafree
      CL (Millipore) ultrafiltration units at various densities. These were incubated
      for varying time intervals with a range of carbon sources. The bacterial films
      reproducibly achieved between 107 and 108 cfu cm-2, irrespective of the number
      inoculated and with no significant changes for 14 d. However, Streptococcus
      mutans grew through membranes with pores of diameter greater than 0.1 microm
      after 6 d. Culture of films in sucrose or water for 6 d led to a decreased number
      of colony-forming units, but returning them to broth reversed this. CONCLUSION:
      Reproducible films of oral bacteria can be cultured in Ultrafree-CL units.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study has shown that Ultrafree-CL
      units can be used as a simple model system to grow biofilms that could be used
      for dental caries research.

PMID- 11442724
TI  - Production of growth-inhibiting factors by Lactobacillus delbrueckii.
AB  - AIMS: The detection of growth-inhibiting factors produced by Lactobacillus
      delbrueckii. METHODS AND RESULTS: A bioscreen assay was developed to study the
      effect of Lact. delbrueckii culture supernatant fluids on the growth of
      phylogenically or functionally related bacteria in broth cultures. Several growth
      inhibiting factors could be distinguished based on differential effects on
      different test strains, separation by ultrafiltration and sensitivity to heat,
      proteinase treatment or catalase addition. CONCLUSION: Lactobacillus delbrueckii
      strain VI1007 was found to produce at least three growth-inhibiting factors,
      other than lactic acid, when grown under microaerobic conditions in MRS broth.
      These included H2O2 and a bacteriocin-like, heat- and proteinase-sensitive
      bactericidal molecule or complex with a molecular weight greater than 50 kDa. A
      third factor inhibited the growth of Streptococcus thermophilus. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The assay system used allows the detection of subtle
      interactions between strains, that are likely to be of ecological importance in
      mixed cultures but would go unnoticed in classical agar diffusion tests.

PMID- 11442725
TI  - Inhibition of adhesion of food-borne pathogens to Caco-2 cells by Lactobacillus
      strains.
AB  - AIMS: To select adhesive strains among strains of Lactobacillus and to apply them
      to inhibit adhesion of food-borne pathogens. METHODS AND RESULTS: Twelve
      Lactobacillus strains (10 from intestine) were examined for adhesion using Caco-2
      cell cultures. The two most adhesive strains, Lactobacillus crispatus JCM 8779
      and Lact. reuteri JCM 1081, were used to test antiadhesion activity against
      enterotoxigenic Escherichia coli, Salmonella typhimurium and Enterococcus
      faecalis strains. Adhesion of the pathogens was inhibited by both Lactobacillus
      strains. Adhesion of Ent. faecalis was especially strongly inhibited by JCM 8779.
      Although antimicrobial activity was not detected in the culture supernatant fluid
      by agar well diffusion assay, the supernatant fluid obtained from the harvested
      JCM 8779 cell suspension showed bactericidal activity against Ent. faecalis.
      CONCLUSION: The strong antiadhesion activity of JCM 8779 against Ent. faecalis
      appears to be due to the combined effect of both bactericidal activity and
      competition for attachment site. SIGNIFICANCE AND IMPACT OF THE STUDY: This is
      the first report that Lact. crispatus produces a bactericidal substance.

PMID- 11442726
TI  - Effect of galactose and glucose on the exopolysaccharide production and the
      activities of biosynthetic enzymes in Lactobacillus casei CRL 87.
AB  - AIMS: The objective of this work was to study the influence of the sugar source
      on exopolysaccharide (EPS) production and the activities of the enzymes involved
      in the synthesis of sugar nucleotides in Lactobacillus casei CRL 87. The
      relationship between these enzymes and EPS formation was determined. METHODS AND
      RESULTS: The concentration of EPS was estimated by the phenol/sulphuric acid
      method while the chemical composition of purified EPS was investigated using gas
      liquid chromatography. Biosynthetic enzyme activities were determined
      spectrophotometrically by measuring the formation or disappearance of NAD(P)H at
      340 nm. Polysaccharide production by Lb. casei CRL 87 was 1.7 times greater on
      galactose than on glucose. The isolated polymer was composed of rhamnose, glucose
      and galactose. The activities of uridine-diphosphate (UDP)-glucose
      pyrophosphorylase, thymidine-diphosphate (dTDP)-glucose-pyrophosphorylase and the
      dTDP-rhamnose-synthetic enzyme system were higher in galactose-grown than in
      glucose-grown cells. When an EPS- mutant strain was used, galactokinase activity
      was not detected on galactose, this sugar not being available for the formation
      of sugar nucleotides for further EPS production. dTDP-glucose-pyrophosphorylase
      and dTDP-rhamnose-synthetic enzyme system activities were lower than the values
      found for the wild type strain. CONCLUSION: The carbon source present in the
      culture medium affects EPS production by Lb. casei CRL 87. The greater polymer
      synthesis by galactose-grown cells is correlated with the higher UDP-glucose
      pyrophosphorylase, dTDP-glucose-pyrophosphorylase and dTDP-rhamnose-synthetic
      enzyme system activities. Initial sugar metabolism is also an important step for
      the synthesis of EPS precursors by this strain. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Knowledge of the effect of the sugar source on EPS production and the
      activities of biosynthetic enzymes provides information about the mechanisms of
      regulation of the synthesis of EPS which can contribute to improving polymer
      production.

PMID- 11442727
TI  - Microscopic observation of aerobic granulation in sequential aerobic sludge
      blanket reactor.
AB  - AIMS: This paper attempts to provide visual evidence of how aerobic granulation
      evolves in sequential aerobic sludge blanket reactors. METHODS AND RESULTS: A
      series of experiments were conducted in two column-type sequential aerobic sludge
      reactors fed with glucose and acetate as sole carbon source, respectively. The
      evolution of aerobic granulation was monitored using image analysis and optical
      and scanning electron microscopy. The results indicated that the formation of
      aerobic granules was a gradual process from seed sludge to compact aggregates,
      further to granular sludge and finally to mature granules with the sequential
      operation proceeding. Glucose- and acetate-fed granules have comparable
      characteristics in terms of settling velocity, size, shape, biomass density and
      microbial activity. However, the microbial diversity of the granules was
      associated with the carbon source supplied. In this work, an important aerobic
      starvation phase was identified during sequential operation cycles. It was found
      that periodical aerobic starvation was an effective trigger for microbial
      aggregation in the reactor and further strengthened cell-cell interaction to form
      dense aggregates, which was an essential step of granulation. The periodical
      starvation-induced aggregates would finally be shaped to granules by hydrodynamic
      shear and flow. CONCLUSION: Aerobic granules can be formed within 3 weeks in the
      systems. The periodical starvation and hydrodynamic conditions would play a
      crucial role in the granulation process. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Aerobic granules have excellent physical characteristics as compared with
      conventional activated sludge flocs. This research could be helpful for the
      development of an aerobic granule-based novel type of reactor for handling high
      strength organic wastewater.

PMID- 11442728
TI  - Prediction of growth of Bacillus megaterium spores as affected by gamma radiation
      dose and spore load.
AB  - AIMS: To provide data on the interaction of radiation dose (x1) and microbial
      contamination load (x2), as predictor variables, on the percentage of vials
      exhibiting growth of Bacillus megaterium spores (y). METHODS AND RESULTS: The
      influence of a wide range of spore loads (1-50 000 spores of B. megaterium vial
      1) and gamma radiation doses (0.2-10 kGy) on the contaminated samples was
      determined. Each contamination load was studied by adding the specified number of
      spores to 100 vials containing nutrient broth and exposing them to various doses
      of gamma radiation. Curves representing the number of contaminated vials against
      the dose of radiation were sigmoidal in shape and the data showed an indirect
      relationship. Data were analysed by regression analysis which revealed a
      significant correlation (R2=0.85). The relationship among the tested variables is
      exponential and can be described by the following equation: y = 1 - (1 -
      e(0.0173x(1)))(x(2)) It was also estimated that, for each increase of 1 in the
      number of spores per vial, there is an increase of 1 in the number of
      contaminated vials. CONCLUSION: The two variables (x1 and x2) have great
      influence on the radiation sterilization efficiency and the proposed mathematical
      model is valid for the prediction of this efficiency. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The results of the present investigation can be of useful industrial
      application and can help to set acceptance and rejection limits for the
      production of materials vulnerable to microbial contamination.

PMID- 11442729
TI  - Screening for the production of extracellular hydrolytic enzymes by non
      Saccharomyces wine yeasts.
AB  - AIMS: The objective of this study was to investigate what types of enzymes are
      being produced by non-Saccharomyces yeasts isolated from grapes in South Africa
      vineyards and clarified grape juice. These enzyme profiles could pave the way for
      attributing specific effects in wine to some of these enzymes produced by so
      called wild yeasts associated with grape must. METHODS AND RESULTS: In this study
      245 yeast isolates, belonging to the genera Kloeckera, Candida, Debaryomyces,
      Rhodotorula, Pichia, Zygosaccharomyces, Hanseniaspora and Kluyveromyces were
      screened for the production of extracellular pectinases, proteases beta
      glucanases, lichenases, beta-glucosidases, cellulases, xylanases, amylases and
      sulphite reductase activity. These yeasts, representing 21 species, were
      previously isolated from grapes and clarified grape juice. The production of all
      extracellular hydrolytic enzymes screened for was observed except beta
      glucosidase activity. The amount and range of enzymes produced varied with
      different isolates of the same species. CONCLUSION: This study clearly revealed
      the potential of non-Saccharomyces wine yeasts to produce a wide range of useful
      extracellular enzymes during the initial phase of wine fermentation. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Enzymes produced by indigenous yeasts associated with
      grapes and juice might be harnessed to catalyse desired biotransformations during
      wine fermentation.

PMID- 11442730
TI  - Validation of smoking status in clinical research into inflammatory periodontal
      disease.
AB  - BACKGROUND: Tobacco smoking is an accepted risk factor for periodontal disease.
      Most studies in the periodontal literature rely on reported smoking habits which
      can be unreliable. This review specifically addresses this problem. METHODS:
      Methods of assessing tobacco smoke exposure, variation in individual smoking
      habits, classification of former/ex-smokers, and validation of abstinence in
      smoking cessation studies receive attention. DISCUSSION: Additionally, clinical
      studies that have examined periodontal health in subjects with validated smoking
      status are discussed.

PMID- 11442731
TI  - Subgingival polishing with a teflon-coated sonic scaler insert in comparison to
      conventional instruments as assessed on extracted teeth (II). Subgingival
      roughness.
AB  - AIM: To assess the root surface roughness and topography on extracted teeth using
      different instruments. MATERIAL AND METHODS: In the present study, laser
      profilometry was used to examine the 3-D roughness values Ra and Rz and
      topography of root surfaces of periodontally-involved teeth instrumented in vivo
      with curette, conventional ultrasonic device, conventional or teflon-coated sonic
      scaler insert, or the Periotor instrument (12 teeth per instrument type), and
      compare these with uninstrumented cementum surfaces. RESULTS: The roughness
      values Ra and Rz of the roots treated with the different instruments showed a
      similar pattern: curettes and the Periotor instrument produced the smoothest
      surfaces (Ra about 1.5 microm, Rz 30 microm); the 4 other instruments created
      similar Ra values of approximately 2-3 microm and Rz roughness of about 50-70
      microm, which equals the untreated root surface. For Ra, the difference between
      the curette or the Periotor instrument and the teflon-coated sonic insert or
      ultrasonic insert was significant, and for Rz, a significant difference was found
      between the curette or the Periotor instrument and ultrasonic insert. As opposed
      to surfaces debrided with the Periotor and teflon-coated sonic scaler, it appears
      that hand instruments markedly reconfigure surfaces. CONCLUSION: The lowest root
      surface roughness values were obtained with hand instruments. The teflon tubing
      on the sonic scaler insert effected no change of topography or roughness as
      compared to uninstrumented, control surfaces. However, it must be pointed out
      that hard-tissue removal was not investigated.

PMID- 11442732
TI  - Molar root anatomy and management of furcation defects.
AB  - BACKGROUND, AIMS: Furcally-involved teeth present unique challenges to the
      success of periodontal therapy. Anatomical and morphological complicating factors
      dictate modifications in treatment approaches used for managing these areas.
      METHOD: Various treatment approaches are available for furcally-involved teeth,
      the choice of which depends on selected interdependent factors. RESULTS: These
      factors, along with various approaches used in the treatment of furcally
      compromised teeth are discussed in this review, with particular emphasis on
      morphology, etiology, classification and diagnosis.

PMID- 11442733
TI  - On the symmetry of periodontal disease.
AB  - BACKGROUND/AIM: Symmetry is a common feature of biological systems, and can be
      observed in multiple aspects of the human body. The purpose of this study was to
      estimate the impact of symmetry on variance observed in intraoral topographic
      distribution patterns of chronic periodontitis. METHOD: This analysis was
      performed on a data set from 56 subjects, including clinical and microbiological
      variables, recorded at the mesial and distal aspect of every tooth in the entire
      dentition. The impact of contralateral conditions was determined on the level of
      the site, the tooth, and the quadrant. RESULTS: Significant correlations were
      detected between probing depths, recession, attachment levels, total cultivable
      bacterial counts and the plaque index recorded on the right and left side on all
      levels of analysis. The odds for bleeding on sampling, as well as for the
      presence of P. intermedia/nigrescens and A. actinomycetemcomitans increased
      significantly if the respective contralateral site was positive for the same
      parameter. In combining ipsilateral and contralateral parameters into the
      analysis it could be shown in several instances that this contralateral effect
      was stronger than the impact of other, ipsilateral factors. As an example, the
      odds for bleeding on sampling increased up to 10 fold if the contralateral site
      was bleeding, whereas the ipsilateral total cultivable count, determined at the
      same site, explained less than 30% of the variation in the bleeding tendency.
      CONCLUSION: These findings support the view that the development of periodontal
      disease in any site cannot be explained by the influence of local detrimental
      factors alone.

PMID- 11442734
TI  - Computer-based intraoral image analysis of the clinical plaque removing capacity
      of 3 manual toothbrushes.
AB  - BACKGROUND: (I) Introducing an intraoral camera system with a special positioner
      to allow computer-based analysis of reproducible images on lingual tooth surfaces
      and (II) comparing plaque removal by three manual toothbrushes with different
      brushhead designs (convex, multilevel and flat trimmed) on lingual mandibular
      tooth surfaces. METHOD: In a clinical single-blind, crossover, 24-h plaque
      regrowth study on 25 subjects, a computer-based index (PPI) was used to evaluate
      pre- and postbrushing plaque on lingual surfaces of mandibular premolars and
      molars. Subjects brushed their teeth under standardized conditions at three
      visits, each time with a different, randomly assigned toothbrush. RESULTS: The
      intraoral camera system allowed a reproducible and relatively convenient access
      to the lingual surfaces of the mandibular teeth and provided an increase in
      objectivity. Overall, each brush achieved statistically significant plaque
      removal, however, none reached clinical relevance. The multilevel brush was
      superior at specific sites, but failed to show statistically significant
      superiority in terms of overall plaque reduction. Without regard of the
      toothbrush used, the right handed subjects were less efficient in removing plaque
      from the right side compared to the left. CONCLUSIONS: The method is able to
      detect even small differences in plaque reduction. None of the different
      brushhead designs was able to compensate an insufficient brushing techniques.

PMID- 11442735
TI  - Utilisation of locally delivered doxycycline in non-surgical treatment of chronic
      periodontitis. A comparative multi-centre trial of 2 treatment approaches.
AB  - AIM: In the present 6-month multicentre trial, the outcome of 2 different
      approaches to non-surgical treatment of chronic periodontitis, both involving the
      use of a locally delivered controlled-release doxycycline, was evaluated.
      MATERIAL AND METHODS: 105 adult patients with moderately advanced chronic
      periodontitis from 3 centres participated in the trial. Each patient had to
      present with at least 8 periodontal sites in 2 jaw quadrants with a probing
      pocket depth (PPD) of > or =5 mm and bleeding following pocket probing (BoP), out
      of which at least 2 sites had to be > or =7 mm and a further 2 sites > or =6 mm.
      Following a baseline examination, including assessments of plaque, PPD, clinical
      attachment level (CAL) and BoP, careful instruction in oral hygiene was given.
      The patients were then randomly assigned to one of two treatment groups:
      scaling/root planing (SRP) with local analgesia or debridement (supra- and
      subgingival ultrasonic instrumentation without analgesia). The "SRP" group
      received a single episode of full-mouth supra-/subgingival scaling and root
      planing under local analgesia. In addition, at a 3-month recall visit, a full
      mouth supra-/subgingival debridement using ultrasonic instrumentation was
      provided. This was followed by subgingival application of an 8.5% w/w doxycycline
      polymer at sites with a remaining PPD of > or =5 mm. The patients of the
      "debridement" group were initially subjected to a 45-minute full-mouth
      debridement with the use of an ultrasonic instrument and without administration
      of local analgesia, and followed by application of doxycycline in sites with a
      PPD of > or =5 mm. At month 3, sites with a remaining PPD of > or =5 mm were
      subjected to scaling and root planing. Clinical re-examinations were performed at
      3 and 6 months. RESULTS: At 3 months, the proportion of sites showing PPD of < or
      =4 mm was significantly higher in the "debridement" group than in the "SRP" group
      (58% versus 50%; p<0.05). The CAL gain at 3 months amounted to 0.8 mm in the
      "debridement" group and 0.5 mm in the "SRP" group (p=0.064). The proportion of
      sites demonstrating a clinically significant CAL gain (> or =2 mm) was higher in
      the "debridement" group than in the "SRP" group (38% versus 30%; p<0.05). At the
      6-month examination, no statistically significant differences in PPD or CAL were
      found between the two treatment groups. BoP was significantly lower for the
      "debridement" group than for the "SRP" group (p<0.001) both at 3- and 6 months.
      The mean total treatment time (baseline and 3-month) for the "SRP" patients was
      3:11 h, compared to 2:00 h for the patients in the "debridement" group (p<0.001).
      CONCLUSION: The results indicate that simplified subgingival instrumentation
      combined with local application of doxycycline in deep periodontal sites can be
      considered as a justified approach for non-surgical treatment of chronic
      periodontitis.

PMID- 11442736
TI  - Relationship between oral health and mortality in cardiovascular diseases.
AB  - BACKGROUND, AIMS: The purpose of the study was to investigate the relationship
      between periodontal health and fatal cardiovascular diseases (CVD). METHODS: The
      investigation was conducted on a sample of 1393 individuals in the County of
      Stockholm. The subjects were examined in an epidemiological study in 1970 with
      respect to dental health. At a follow-up in 1997, the mortality rate of the
      sample during the years 1970-1996 was registered as well as cause of death
      according to the death certificate. Stepwise logistic regression analysis was
      performed in order to evaluate the influence of the investigated variables on the
      incidence of death from CVD. RESULTS: The interactional effect between plaque and
      oral health score (a sum of scores for number of missing teeth, apical lesions,
      caries lesions and marginal bone loss), adjusted for age, gender, smoking and CVD
      at baseline, was significantly correlated to fatal coronary events. For
      individuals younger than 45 years of age, the age-adjusted incidence odds ratio
      of death due to CVD was 2.7 (p=0.04) if subjects with mean marginal bone loss of
      >10% were compared with subjects with mean marginal bone loss < or =10 %. If the
      stratum of individuals <45 years of age is confined to smokers, the odds ratio
      was found to be 3.4 (p=0.03). CONCLUSION: Dental health was found to be a risk
      indicator of death due to CVD, especially in combination with another risk
      factor, smoking habits.

PMID- 11442737
TI  - Effect of nicotine-treated epithelial cells on the proliferation and collagen
      production of gingival fibroblasts.
AB  - BACKGROUND, AIMS: Several in vitro and in vivo studies have indicated that
      tobacco smoking may be an important risk factor for the development and severity
      of inflammatory periodontal disease. METHOD: In the present study, we developed
      an in vitro model to study the interactions between nicotine-treated epithelial
      cells (EC) and gingival fibroblasts (GF) derived from the same patient. EC were
      treated with nicotine concentrations varying from 1 microg/ml to 500 microg/ml
      and their effect on different functions of GF was studied. The proliferation of
      GF was evaluated by the incorporation of 3H-thymidine. A dose-dependent
      inhibition was observed with nicotine concentrations > or =100 microg/ml. Similar
      results were observed when studying the total protein synthesis of GF by
      incorporation of 3H-proline into non-dialyzable material. RESULTS: When collagen
      production was evaluated by 3H-proline incorporation into collagenase-sensitive
      protein, a dose-dependent reduction was observed: the degree of inhibition varied
      from 25% with 50 microg/ml nicotine, to almost 60% with 500 microg/ml.
      Interestingly, the production of non-collagenous proteins decreased by almost 50%
      only when EC were treated with the highest concentration of nicotine.
      CONCLUSIONS: The results suggest that epithelial cells, acting as mechanical
      barrier, can reduce but not completely eliminate the deleterious effect of
      nicotine on gingival fibroblasts.

PMID- 11442738
TI  - Effects of metal salts on the oral production of volatile sulfur-containing
      compounds (VSC).
AB  - BACKGROUND/AIM: Halitosis, mainly caused by bacteria located on the posterior
      dorsum of the tongue and in periodontal pockets, is due to formation of volatile
      sulfur compounds (VSC). The hypothesis to be tested was that the affinity of a
      metal for sulfur determines its anti-VSC activity. METHOD: Clinical tests were
      carried out on 12 subjects who rinsed with cysteine to induce halitosis
      (baseline) before rinsing with 7.34 mM ZnCl2, SnF2 and CuCl2. Mouth air VSC
      analyses were repeated following cysteine rinses at 1 h, 2 h and 3 h using a gas
      chromatograph. In vitro experiments tested toxic metals Hg2+, Pb2+ and Cd2+. 10
      microl aliquots of metal salts were added to 1-ml aliquots of human whole saliva
      from 30 subjects. Samples were incubated overnight at 37oC and saliva headspace
      was analyzed for VSC in a gas chromatograph. CLINICAL RESULTS: Cu2+>Sn2+>Zn2+
      (supports hypothesis). Zn2+ had significantly less anti-VSC effect compared with
      Cu2+ and Sn2+ at 1, 2 and 3 h. In vitro results indicated that Hg2+, Cu2+ and
      Cd2+ had close to 100% anti-VSC effect, and that Pb2+ was less effective and Cd2+
      more effective than expected in inhibiting VSC. CONCLUSIONS: Apart from Hg2+ and
      Cu2+, the metals had a significantly greater effect on H2S than on CH3SH. Cu2+
      and Hg2+ have well-known antibacterial activity and may presumably also operate
      by this mechanism.

PMID- 11442739
TI  - Subantimicrobial dose doxycycline as an adjunct to scaling and root planing: post
      treatment effects.
AB  - BACKGROUND/OBJECTIVE: Subantimicrobial dose doxycycline (SDD 20 mg bid) plus
      scaling and root planing (SRP) significantly improved clinical attachment level
      (CAL) and reduced probing depth (PD) compared with placebo plus SRP in a double
      blind, placebo-controlled, multicenter study of patients with adult periodontitis
      (AP). In a study conducted as a follow-up, the post-treatment effects of SDD were
      assessed in patients who completed the SRP study. METHODS: The SRP study was a 9
      month, active-treatment study and the follow-up was a 3-month, no-treatment
      study. In the SRP study, tooth sites in qualifying quadrants were scaled and root
      planed and patients were randomized to receive twice daily SDD 20 mg or placebo.
      In the follow-up, patients received no study drug; investigators and patients
      remained blinded to the previous treatment group assignments. Efficacy measures
      included the change in CAL and PD from baseline values determined at the start of
      the SRP study in tooth sites stratified by baseline PD (i.e., 0-3 mm, 4-6 mm, >
      or =7 mm). Safety was evaluated using adverse event data and the results of
      clinical laboratory tests, oral pathology examinations, and microbiological
      assessments. RESULTS: Within each disease stratum, the incremental improvements
      in PD and CAL demonstrated in the SDD group over 9 months of active treatment
      were maintained through 3 additional months of no treatment. Treatment cessation
      did not result in an accelerated regression of periodontal health. No differences
      in the incidence of adverse events (including those related to infection) or
      laboratory or microbiological parameters were noted between the SDD group and the
      placebo group. CONCLUSIONS: The administration of SDD 20 mg bid for a period of
      up to 9 months is not associated with rebound effects or delayed or negative
      after-effects for a 3-month period after cessation of therapy.

PMID- 11442740
TI  - Pre-treatment conceptions of periodontal disease and treatment in periodontal
      referrals.
AB  - BACKGROUND: Patients preconceptions of periodontal therapy have not been
      extensively studied and are poorly understood. AIMS: To register specific
      anxieties and preconceptions held by patients referred for specialist periodontal
      treatment and to investigate the risks such patients were prepared to take of
      progressive periodontal problems before deciding that periodontal treatment was
      necessary. MATERIALS AND METHODS: 79 patients referred for specialist treatment
      completed a structured questionnaire. Participants completed visual analogue
      scales to quantify the risks which they were prepared to take of various symptoms
      of periodontal disease before they believed treatment was essential. RESULTS: The
      majority (71%) had anxieties about pending treatment with the main concern being
      pain. Those who had sought information prior to treatment mainly did so from
      close relatives. The majority of patients opted to take no or a very low (<20%)
      risk of any periodontal problems and, therefore, were supportive of treatment.
      The loss of many teeth due to periodontal disease was the least acceptable
      outcome followed by tooth mobility. Patients were prepared to accept a
      significantly higher risk of bleeding on brushing (p<0.0001) than any of the
      other outcomes investigated. Females recorded substantially lower risk scores
      than males particularly in relation to developing recession or tooth mobility in
      the absence of treatment. Patients who were worried about experiencing pain
      during treatment recorded lower risk scores than those who had no anxiety
      regarding pain. CONCLUSION: It is concluded that the Norwegian periodontal
      referrals studied were prepared to take very low risks of further periodontal
      symptoms despite high levels of anxiety and evidence of a lack of knowledge
      regarding periodontal treatment.

PMID- 11442741
TI  - Changes in subgingival microflora and humoral immune response following
      periodontal therapy.
AB  - OBJECTIVES: To investigate the effect of scaling and root planing (SRP) on the
      microflora and humoral immune response in adult periodontitis. MATERIALS &
      METHODS: Clinical measurements, subgingival plaque samples, gingival crevicular
      fluid and sera were taken from 4 sites in 28 adult periodontitis patients before
      and after SRP. Polymerase chain reaction was used to determine the presence of A.
      actinomycetemcomitans, P. gingivalis, B. forsythus, P. intermedia, and T.
      denticola. ELISA was used to investigate the systemic and local antibody titres
      to these organisms, and thiocyanate dissociation for the determination of serum
      antibody avidity. RESULTS: SRP produced a good clinical improvement. On a subject
      basis there was little significant change in the microflora. However, on a site
      basis, there were significant reductions in P. intermedia, B. forsythus and T.
      denticola. There was little change in systemic and local antibody titres
      following SRP, although there was a significant reduction in antibody avidity to
      P. gingivalis and P. intermedia CONCLUSION: Post-therapy clinical improvement was
      associated with a reduction in bacterial prevalence, but statistical significance
      was only reached at a site level and this microbial reduction was not significant
      for all organisms. No significant post-therapy effects on the humoral immune
      response were noted other than a reduced antibody avidity to P. gingivalis and P.
      intermedia. The lack of a clear pattern in the humoral immune response may
      reflect a failure of the host response to produce adequate levels of biologically
      functional antibodies, and complex interactions between the subgingival flora and
      the host response.

PMID- 11442742
TI  - Comparison of the validity of periodontal probing measurements in smokers and non
      smokers.
AB  - AIM: To determine whether the reduced inflammation and bleeding and increased
      fibrosis reported in tobacco smokers affect the validity of clinical probing
      measurements by altering probe tip penetration. METHOD: A constant force probe
      was used to measure probing depths and sound bone levels at six sites on 64 molar
      teeth (384 sites) in 20 smoking and 20 non-smoking patients from grooves made
      with a bur at the gingival margin prior to extraction. Connective tissue
      attachment levels were measured from the grooves with a dissecting microscope
      following extraction. Data were analysed using robust regression with sites
      clustered within subjects. RESULTS: Sites in smokers showed more calculus but
      less bleeding than sites in non-smokers (p<0.05). The mean clinical probing depth
      was not significantly different (smokers: 5.54 mm, confidence intervals=4.81 to
      6.28; non-smokers: 6.05 mm, ci=5.38 to 6.72). The corresponding post-extraction
      pocket depth measurements (smokers: 4.95 mm, ci=4.30 to 5.61; non-smokers: 5.23
      mm, ci=4.49 to 5.96) were less than clinical probing depth in sites from both
      smokers and non-smokers (p<0.01). However, the proportional difference was less
      in smokers (p<0.05), particularly in deeper pockets, indicating that clinical
      probe tip penetration of tissue was greater in non-smokers. Regression analysis
      indicated that the presence of calculus and bleeding also influenced the
      difference in clinical probe penetration (p<0.05). CONCLUSION: Clinical probing
      depth at molar sites exaggerates pocket depth, but the probe tip may be closer to
      the actual attachment level in smokers due to less penetration of tissue. This
      may be partly explained by the reduced inflammation and width of supra-bony
      connective tissue in smokers. These findings have clinical relevance to the
      successful management of periodontal patients who smoke.

PMID- 11442743
TI  - Life and death signaling in epidermis: following a planned cell death pathway
      involving a trail that does not lead to skin cancer.

PMID- 11442744
TI  - A comprehensive guide for the accurate classification of murine hair follicles in
      distinct hair cycle stages.
AB  - Numerous strains of mice with defined mutations display pronounced abnormalities
      of hair follicle cycling, even in the absence of overt alterations of the skin
      and hair phenotype; however, in order to recognize even subtle, hair cycle
      related abnormalities, it is critically important to be able to determine
      accurately and classify the major stages of the normal murine hair cycle. In this
      comprehensive guide, we present pragmatic basic and auxiliary criteria for
      recognizing key stages of hair follicle growth (anagen), regression (catagen) and
      quiescence (telogen) in C57BL/6NCrlBR mice, which are largely based on previous
      work from other authors. For each stage, a schematic drawing and representative
      micrographs are provided in order to illustrate these criteria. The basic
      criteria can be employed for all mouse strains and require only routine
      histochemical techniques. The auxiliary criteria depend on the
      immunohistochemical analysis of three markers (interleukin-1 receptor type I,
      transforming growth factor-beta receptor type II, and neural cell-adhesion
      molecule), which allow a refined analysis of anatomical hair follicle
      compartments during all hair cycle stages. In contrast to prior staging systems,
      we suggest dividing anagen III into three distinct substages, based on
      morphologic differences, onset and progression of melanogenesis, and the position
      of the dermal papilla in the subcutis. The computer-generated schematic
      representations of each stage are presented with the aim of standardizing reports
      on follicular gene and protein expression patterns. This guide should become a
      useful tool when screening new mouse mutants or mice treated with pharmaceuticals
      for discrete morphologic abnormalities of hair follicle cycling in a highly
      reproducible, easily applicable, and quantifiable manner.

PMID- 11442745
TI  - In vitro visualization and quantification of oleic acid induced changes in
      transdermal transport using two-photon fluorescence microscopy.
AB  - In a novel application of two-photon scanning fluorescence microscopy, three
      dimensional spatial distributions of the hydrophilic and hydrophobic fluorescent
      probes, sulforhodamine B and rhodamine B hexyl ester, in excised full-thickness
      human cadaver skin were visualized and quantified. Both sulforhodamine B and
      rhodamine B hexyl ester were observed to lie primarily in the lipid multilamellae
      region surrounding the corneocytes within the stratum corneum. From the two
      photon scanning fluorescence microscopy scans, the changes in the concentration
      gradient and the vehicle to skin partition coefficient of each probe induced by
      the oleic acid enhancer action were calculated relative to the control sample
      (not exposed to oleic acid), and subsequently applied to theoretically derived
      mathematical expressions of transdermal transport to quantitatively characterize
      the oleic acid-induced relative changes in the skin diffusion coefficient and the
      skin barrier diffusion length of the permeant. For the hydrophobic probe
      rhodamine B hexyl ester, the permeability enhancement was primarily driven by an
      increase in the vehicle to skin partition coefficient, leading to an increase in
      the steepness of the concentration gradient across the skin. The primary oleic
      acid-induced changes in the transport properties of the hydrophilic probe
      sulforhodamine B included increases in the vehicle to skin partition coefficient
      and the skin diffusion coefficient. These findings utilizing the two-photon
      scanning fluorescence microscopy methodology and data analysis described here
      demonstrate that, in addition to providing three-dimensional images that clearly
      delineate probe distributions in the direction of increasing skin depth, the
      subsequent quantification of these images provides additional important insight
      into the mechanistic changes in transdermal transport underlying the visualized
      changes in probe distributions across the skin.

PMID- 11442746
TI  - Assembly of desmosomal cadherins into desmosomes is isoform dependent.
AB  - Desmosomes are intercellular adhesive junctions that exhibit cell- and
      differentiation-specific differences in their molecular composition. In complex
      epithelia, desmosomes contain multiple representatives of the desmosomal cadherin
      family, which includes three desmogleins and three desmocollins. Rules governing
      the assembly of desmosomal cadherin isoforms into desmosomes of different cell
      types are unknown. Here we compared the assembly properties of desmoglein 2
      (Dsg2) and desmocollin 2 (Dsc2), which are widely expressed, with Dsg1 and Dsc1,
      which are expressed in the differentiated layers of complex epithelia, by
      introducing myc-tagged forms into simple and squamous epithelial cells that do
      not express Dsg1 or Dsc1. Dsc2.myc and Dsg2.myc assembled efficiently into
      desmosomes in every cell type in spite of significant shifts in the
      stoichiometric relationship between desmogleins and desmocollins. In contrast,
      Dsc1a.myc, Dsc1b.myc, and Dsg1.myc did not stably incorporate into desmosomes in
      any line. Coexpression of Dsc1a.myc or Dsc1b.myc and Dsg1.myc did not lead to
      their colocalization and failed to enhance incorporation of either cadherin into
      desmosomes. Dsg1.myc, but not Dsc1a, Dsc1b, disrupted desmosome assembly in a
      cell-type-specific manner, and disruption correlated with the recruitment of
      Dsg1.myc, but not Dsc1a or Dsc1b, into a Triton-insoluble pool. The plakoglobin:E
      cadherin ratio decreased in Dsg1-expressing cells with disrupted desmosomes, but
      a decrease was also observed in a Dsc1a line. Thus, a modest reduction of
      plakoglobin associated with E-cadherin is apparently not sufficient to disrupt
      desmosome assembly. Our results demonstrate that desmosome assembly tolerates
      large shifts in cadherin stoichiometry, but is sensitive to isoform-specific
      differences exhibited by desmogleins and desmocollins.

PMID- 11442747
TI  - 15-Lipoxygenase-2 expression in benign and neoplastic sebaceous glands and other
      cutaneous adnexa.
AB  - 15-Lipoxygenase-2 has a limited tissue distribution in epithelial tissues, with
      mRNA detected in skin, cornea, lung, and prostate. It was originally cloned from
      human hair rootlets. In this study the distribution of 15-lipoxygenase-2 was
      characterized in human skin using immunohistochemistry and in situ hybridization.
      Strong uniform 15-lipoxygenase-2 in situ hybridization (n = 6) and immunostaining
      (n = 16) were observed in benign cutaneous sebaceous glands, with expression in
      differentiated secretory cells. Strong 15-lipoxygenase-2 immunostaining was also
      observed in secretory cells of apocrine and eccrine glands. Variable reduced
      immunostaining was observed in skin-derived sebaceous neoplasms (n = 8). In the
      eyelid, Meibomian glands were uniformly negative for 15-lipoxygenase-2 in all
      cases examined (n = 9), and sebaceous carcinomas apparently derived from
      Meibomian glands were also negative (n = 12). The mechanisms responsible for
      differential expression in cutaneous sebaceous vs eyelid Meibomian glands remain
      to be established. In epidermis, positive immunostaining was observed in the
      basal cell layer in normal skin, whereas five examined basal cell carcinomas were
      negative. Thus, the strongest 15-lipoxygenase-2 expression is in the androgen
      regulated secretory cells of sebaceous, apocrine, and eccrine glands. This
      compares with the prostate, in which 15-lipoxygenase-2 is expressed in
      differentiated prostate secretory cells (and reduced in the majority of prostate
      adenocarcinomas). The product of 15-lipoxygenase-2, 15-hydroxyeicosatetraenoic
      acid, may be a ligand for the nuclear receptor peroxisome proliferator activated
      receptor-gamma, which is expressed in sebocytes, and contribute to secretory
      differentiation in androgen regulated tissues such as prostate and sebaceous
      glands.

PMID- 11442748
TI  - Generation of free fatty acids from phospholipids regulates stratum corneum
      acidification and integrity.
AB  - There is evidence that the "acid mantle" of the stratum corneum is important for
      both permeability barrier formation and cutaneous antimicrobial defense. The
      origin of the acidic pH of the stratum corneum remains conjectural, however. Both
      passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g.,
      proton pumps) mechanisms have been proposed. We assessed here whether the free
      fatty acid pool, which is derived from phospholipase-mediated hydrolysis of
      phospholipids during cornification, contributes to stratum corneum acidification
      and function. Topical applications of two chemically unrelated secretory
      phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3
      trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the
      pH of murine skin surface that was paralleled not only by a permeability barrier
      abnormality but also altered stratum corneum integrity (number of strippings
      required to break the barrier) and decreased stratum corneum cohesion (protein
      weight removed per stripping). Not only stratum corneum pH but also all of the
      functional abnormalities normalized when either palmitic, stearic, or linoleic
      acids were coapplied with the inhibitors. Moreover, exposure of intact murine
      stratum corneum to a neutral pH for as little as 3 h produced comparable
      abnormalities in stratum corneum integrity and cohesion, and further amplified
      the inhibitor-induced functional alterations. Furthermore, short-term
      applications of an acidic pH buffer to inhibitor-treated skin also reversed the
      abnormalities in stratum corneum integrity and cohesion, despite the ongoing
      decrease in free fatty acid levels. Finally, the secretory-phospholipase
      inhibitor-induced alterations in integrity/cohesion were in accordance with
      premature dissolution of desmosomes, demonstrated both by electron microscopy and
      by reduced desmoglein 1 levels in the stratum corneum (shown by
      immunofluorescence staining and visualized by confocal microscopy). Together,
      these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid
      processing for normal stratum corneum acidification; and (ii) the potentially
      important role of this pathway not only for barrier homeostasis but also for the
      dual functions of stratum corneum integrity and cohesion.

PMID- 11442749
TI  - Ultraviolet-radiation-induced keratinocyte apoptosis in C1q-deficient mice.
AB  - Exposure to ultraviolet B radiation is an important trigger of both systemic and
      cutaneous disease flares in individuals with systemic lupus erythematosus. More
      than 90% of individuals with homozygous C1q deficiency develop a systemic-lupus
      erythematosus-like illness, which is typically associated with a severe
      photosensitive rash. Apoptotic, human keratinocytes have been shown in vitro to
      bind C1q, in the absence of antibody. These observations, together with the
      hypothesis that a major source of the autoantigens driving the immune response in
      systemic lupus erythematosus comes from apoptotic cells, led us to investigate
      the effects of murine C1q deficiency on ultraviolet-radiation-induced
      keratinocyte apoptosis in vivo. In this work, we demonstrated C1q binding to
      apoptotic murine keratinocytes in vitro and showed for the first time that C1q is
      also present on sunburn cells in vivo. In addition to C1q, we detected C3
      deposition on sunburn cells in both wild-type and C1q-deficient mice, suggesting
      activation of the alternative pathway. Following acute ultraviolet exposure in
      vivo, no difference in the rate of clearance of sunburn cells was found in C1q
      deficient mice from three different genetic backgrounds, compared with strain
      matched wild-type controls. Furthermore, chronic ultraviolet exposure did not
      result in the production of autoantibodies or the development of
      glomerulonephritis. Our findings suggest that C1q does not play a critical role
      in the physiologic clearance of apoptotic murine keratinocytes in vivo.

PMID- 11442750
TI  - Ultraviolet light downregulates CD95 ligand and TRAIL receptor expression
      facilitating actinic keratosis and squamous cell carcinoma formation.
AB  - Long-term ultraviolet light exposure of human skin epidermis in Caucasians is
      associated with an increased risk for the development of melanoma and nonmelanoma
      skin cancers. Ultraviolet radiation not only induces DNA damage in epidermal
      cells, it also interferes with skin homeostasis, which is maintained by a unique
      distribution pattern of apoptosis-inducing and apoptosis-preventing molecules. We
      demonstrate that, beside CD95 ligand, TRAIL and TRAIL receptors also function as
      important sensors in the human epidermis preserving skin integrity and preventing
      cell transformation. Ultraviolet irradiation extensively changes the expression
      pattern of some of these molecules, diminishing their sensor function. In
      particular, CD95 ligand and to a somewhat lesser extent TRAIL receptors are
      downregulated upon ultraviolet light exposure. CD95 ligand downregulation is not
      due to protein degradation as in situ hybridization experiments strongly support
      a transcriptional regulation. The downregulation of these molecules with sensor
      function increases the risk that aberrant cells are less efficiently eliminated.
      This concept is supported by the fact that the expression of these molecules is
      also low or absent in actinic keratosis, a precancerous state that has developed
      as the consequence of long-term ultraviolet exposure. Progression to invasive
      neoplasms is then accompanied by an upregulation of CD95 ligand and a
      downregulation of CD95 and of the TRAIL receptors. The high expression of CD95
      ligand, TRAIL, and FLIP in squamous cell carcinoma may then contribute to the
      immune escape of the tumor, whereas the lack of expression of CD95 and TRAIL
      receptors prevents autolysis of the tumor.

PMID- 11442751
TI  - Expression of the alphavbeta6 integrin promotes migration and invasion in
      squamous carcinoma cells.
AB  - The integrin alphavbeta6 is a fibronectin receptor whose expression is not
      detectable on normal oral epithelium but is increased significantly in healing
      and in oral epithelial dysplasia and oral squamous cell carcinoma, suggesting it
      may promote changes associated with tumor development. To study whether
      alphavbeta6 may drive invasive behavior we have used transfection and retroviral
      infection to create a panel of epithelial cell lines expressing various levels of
      alphavbeta6. We report that increased expression of alphavbeta6 in malignant
      keratinocytes promotes invasion and leads to an increased capacity for migration
      towards fibronectin. alphavbeta6 expression may have a significant role in
      contributing to the malignant behavior of epithelial cells.

PMID- 11442752
TI  - Peroxynitrite production, DNA breakage, and poly(ADP-ribose) polymerase
      activation in a mouse model of oxazolone-induced contact hypersensitivity.
AB  - Peroxynitrite-induced poly(ADP-ribose) polymerase activation has been implicated
      in the pathogenesis of various inflammatory conditions. Here we have investigated
      whether peroxynitrite and poly(ADP-ribose) polymerase may play a role in the
      pathophysiology of the elicitation phase of contact hypersensitivity. We have
      detected nitrotyrosine, DNA breakage, and poly(ADP-ribose) polymerase activation
      in the epidermis of mice in an oxazolone-induced contact hypersensitivity model.
      As tyrosine nitration is mostly mediated by peroxynitrite, a nitric-oxide-derived
      cytotoxic oxidant capable of causing DNA breakage, we have applied peroxynitrite
      directly on mouse skin and showed poly(ADP-ribose) polymerase activation in
      keratinocytes and in some scattered dermal cells. We have also investigated the
      cellular effects of peroxynitrite in HaCaT cells, a human keratinocyte cell line.
      We found that peroxynitrite inhibited cell proliferation and at higher
      concentrations also caused cytotoxicity. Peroxynitrite activates poly(ADP-ribose)
      polymerase in HaCaT cells and poly(ADP-ribose) polymerase activation contributes
      to peroxynitrite-induced cytotoxicity, as indicated by the cytoprotective effect
      of the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide. The cytoprotective
      effect of 3-aminobenzamide cannot be attributed to inhibition of apoptosis, as
      apoptotic parameters (caspase activation and DNA fragmentation) were not reduced
      in the presence of 3-aminobenzamide in peroxynitrite-treated cells. Moreover,
      poly(ADP-ribose) polymerase inhibition by 3-aminobenzamide dose-dependently
      reduced interferon-induced intercellular adhesion molecule 1 expression as well
      as interleukin-1beta-induced interleukin-8 expression. Our results indicate that
      peroxynitrite and poly(ADP-ribose) polymerase regulate keratinocyte function and
      death in contact hypersensitivity.

PMID- 11442753
TI  - Identification of rab7 as a melanosome-associated protein involved in the
      intracellular transport of tyrosinase-related protein 1.
AB  - The melanosome is a unique secretory granule of the melanocyte in which melanin
      pigments are synthesized by tyrosinase gene family glycoproteins. Melanogenesis
      is a highly regulated process because of its inherent toxicity. An understanding
      of the various regulatory mechanisms is important in delineating the
      pathophysiology involved in pigmentary disorders and melanoma. We have purified
      and analyzed the total melanosomal proteins from B16 mouse melanoma tumors in
      order to identify new proteins that may be involved in the control of the
      melanogenesis process. Melanosomal proteins were resolved by two-dimensional
      sodium dodecyl sulfate polyacrylamide gel electrophoresis, a predominant spot (27
      kDa with isoelectric point 5.8-6.4) was excised and digested with cyanogen
      bromide, and the fragments were sequenced. Synthetic oligonucleotide primers were
      synthesized corresponding to the peptide sequences, and reverse transcriptase
      polymerase chain reaction amplification of total RNA from B16 cells was carried
      out. Sequencing of one of the polymerase-chain-reaction-mediated clones
      demonstrated 80%-97% sequence homology of 200 bp nucleotide with GTP-binding
      proteins at the 3'-untranslated region. GTP-binding assay on two-dimensional gels
      of melanosomal proteins showed the presence of several (five to six) small GTP
      binding proteins, suggesting that small GTP-binding proteins are associated with
      the melanosome. Among the known GTP-binding proteins with similar molecular
      weight and isoelectric point ranges, rab3, rab7, and rab8 were found to be
      present in the melanosomal fraction by immunoblotting. Confocal
      immunofluorescence microscopy showed that rab7 is colocalized with the tyrosinase
      related protein 1 around the perinuclear area as well as, in part, in the
      perikaryon, thereby suggesting that rab7 might be involved in the intracellular
      transport of tyrosinase-related protein 1. Tyrosinase-related protein 1 transport
      was blocked by the treatment of B16 cells with antisense oligonucleotide to rab7.
      We suggest (i) that rab7 is a melanosome-associated molecule, (ii) that
      tyrosinase-related protein 1 is present in late-endosome delineated granules, and
      (iii) that rab7 is involved in the transport of tyrosinase-related protein 1 from
      the late-endosome delineated granule to the melanosome.

PMID- 11442754
TI  - Cutaneous injury induces the release of cathelicidin anti-microbial peptides
      active against group A Streptococcus.
AB  - Cathelicidins are a family of peptides thought to provide an innate defensive
      barrier against a variety of potential microbial pathogens. The human and mouse
      cathelicidins (LL-37 and CRAMP, respectively) are expressed at select epithelial
      interfaces where they have been proposed to kill a number of gram-negative and
      gram-positive bacteria. To determine if these peptides play a part in the
      protection of skin against wound infections, the anti-microbial activity of LL-37
      and CRAMP was determined against the common wound pathogen group A Streptococcus,
      and their expression was examined after cutaneous injury. We observed a large
      increase in the expression of cathelicidins in human and murine skin after
      sterile incision, or in mouse following infection by group A Streptococcus. The
      appearance of cathelicidins in skin was due to both synthesis within epidermal
      keratinocytes and deposition from granulocyctes that migrate to the site of
      injury. Synthesis and deposition in the wound was accompanied by processing from
      the inactive prostorage form to the mature C-terminal peptide. Analysis of anti
      microbial activity of this C-terminal peptide against group A Streptococcus
      revealed that both LL-37 and CRAMP potently inhibited bacterial growth. Action
      against group A Streptococcus occurred in conditions that typically abolish the
      activity of anti-microbial peptides against other organisms. Thus, cathelicidins
      are well suited to provide defense against infections due to group A
      Streptococcus, and represent an important element of cutaneous innate immunity.

PMID- 11442755
TI  - A novel keratinocyte mitogen: regulation of leptin and its functional receptor in
      skin repair.
AB  - Wound re-epithelialization represents a tissue movement that crucially
      participates in wound closure. Recently, we demonstrated that supplemented leptin
      improved re-epithelialization processes in leptin-deficient ob/ob mice. In this
      study we investigated regulation of the leptin system during normal repair in
      healthy animals. We found leptin to be present at the wound site during healing,
      although leptin levels were clearly reduced upon injury compared with uninvolved
      control skin. The functional leptin receptor subtype obRb was observed to be
      constitutively expressed in nonwounded skin. During early healing, the leptin
      receptor obRb was downregulated, but re-increased again from day 5 postwounding.
      Immunohistochemistry revealed that highly proliferative keratinocytes of the
      wound margin epithelia strongly expressed the functional leptin receptor subtype
      obRb. In vitro studies demonstrated that murine and human primary epidermal
      keratinocytes responded to exogenously added leptin with a proliferative
      response. Moreover, specificity of leptin-mediated mitogenic effects on primary
      keratinocytes could be shown by completely blocking leptin actions by a soluble,
      nonfunctional chimeric leptin receptor. Finally, we report that leptin, besides
      the recently described activation of the janus tyrosine kinase signal
      transducers, also activated extracellular signal-regulated kinase-controlled
      signaling pathways in primary keratinocytes.

PMID- 11442756
TI  - Expression of the peptide antibiotics human beta defensin-1 and human beta
      defensin-2 in normal human skin.
AB  - Normal human skin is remarkably resistant to infection from the large numbers of
      microorganisms that routinely colonize its surface. In addition to the role of
      skin as a mechanical barrier, it has long been recognized that skin and other
      epithelia can produce a range of anti-microbial chemicals that play an important
      part in eliminating potential cutaneous pathogens. Anti-microbial peptides are an
      important evolutionarily conserved innate host defense mechanism in many
      organisms. Human beta defensin-1 and -2 are cysteine-rich, cationic, low
      molecular weight anti-microbial peptides that have recently been shown to be
      expressed in epithelial tissues. In this study, we describe the characterization
      of human beta defensin-1 and -2 mRNA and peptide expression in normal human skin.
      Using reverse transcription-polymerase chain reaction we demonstrate that human
      beta defensin-1 is consistently expressed in skin samples from various body
      sites. Human beta defensin-2 demonstrates expression that is more variable and is
      more readily detectable in facial skin and foreskin compared with skin from
      abdomen and breast. In situ hybridization localizes the human beta defensin-1 and
      -2 transcripts to keratinocytes within interfollicular skin. Using specific
      antibodies, we have shown that human beta defensin-1 and -2 peptides are
      localized to the Malpighian layer of the epidermis and/or stratum corneum and
      that there are interindividual and site-specific differences in intensity of
      immunostaining and the pattern of peptide localization. The localization of human
      beta defensins to the outer layer of the skin is consistent with the hypothesis
      that human beta defensins play an essential part in cutaneous innate immunity.

PMID- 11442757
TI  - Modification of fibroblast gamma-interferon responses by extracellular matrix.
AB  - Fibroblasts from scaffold-based three-dimensional human cultures have been
      demonstrated to colonize ulcer wound beds and persist for at least 6 mo without
      rejection. This study examines the expression in these cultures of molecules
      associated with activation of the immune system in acute rejection. Studies in
      monolayer cultures showed that fibroblasts expressed CD40 at about 10% of the
      surface density seen in umbilical vein endothelial cells, whereas HLA-DR was
      undetectable. In these cultures, both molecules were induced by gamma-interferon.
      In scaffold-based three-dimensional cultures, however, a majority of the
      fibroblasts showed little induction of CD40 and HLA-DR in response to gamma
      interferon, although HLA class I expression was increased. Fibroblasts re-
      isolated from the three-dimensional cultures and cultured in monolayers recovered
      HLA-DR induction in response to gamma-interferon. Fibroblasts cultured in an
      alternative three-dimensional system using collagen gels showed CD40 and HLA-DR
      induction by gamma-interferon in the same manner as monolayer cultures.
      Comparison of phosphorylation of signal transducer and activator of transcription
      1 on tyrosine-701 showed it to be similar in monolayer and three-dimensional
      culture, and phospho-signal transducer and activator of transcription 1 moved
      into the nucleus. Induction of the class II transcription activator was greatly
      reduced, however. We propose that interaction of fibroblasts with the fibroblast
      derived extracellular matrix is an important modulator of gamma-interferon
      responsiveness and that this interaction may play a role in the low
      immunogenicity of allogeneic fibroblasts grown on scaffolds.

PMID- 11442758
TI  - Dysregulation of lymphocyte interleukin-12 receptor expression in Sezary
      syndrome.
AB  - Initial phase I and II clinical trials with recombinant human interleukin-12 have
      demonstrated the therapeutic efficacy of this cytokine in early stage cutaneous T
      cell lymphoma as compared with more advanced stages such as the leukemic Sezary
      syndrome. In an effort to optimize the use of recombinant human interleukin-12,
      using flow cytometry we studied the regulation of the interleukin-12 receptor
      beta1 (high affinity chain) and beta2 (chain necessary for interleukin-12 signal
      transduction) on normal volunteer CD4+ and CD8+ T cells and CD4+ and CD8+ cells
      from eight patients with different degrees of leukemic involvement with Sezary
      syndrome. The beta1 chain was not readily detectable on resting normal and T
      cells from Sezary patients, but expression was induced following T cell
      activation with phytohemagglutinin. Similarly, the beta2 chain was not detectable
      on resting normal volunteer T cells, but could be induced following
      phytohemagglutinin stimulation. Moreover, the beta2 chain on normal volunteer T
      cells was markedly upregulated following short-term culture with interferon-gamma
      or recombinant human interleukin-12. CD8+ T cells routinely exhibited a greater
      expression of beta2 than did CD4+ T cells. In marked contrast, both CD4+ and CD8+
      T cells from patients with Sezary syndrome and a high tumor cell burden (> 50%
      circulating atypical Sezary T cells) failed to express the beta2 chain under any
      culture conditions. Although, culture with anti-interleukin-10 also markedly
      increased beta2 expression on normal volunteer T cells, this failed to induce
      expression on either CD4+ or CD8+ T cells from Sezary patients and a high tumor
      burden. Investigation of patients with Sezary syndrome and a low tumor cell
      burden (< 15% circulating Sezary T cells) revealed a pattern of beta2 expression
      that was intermediate between advanced Sezary syndrome and normal volunteers.
      Both CD4+ and CD8+ peripheral blood T cells from these earlier stage patients
      were induced to express the beta2 chain, although at a lower frequency of
      positivity than T cells from normals, following culture with phytohemagglutinin,
      interferon-gamma, recombinant human interleukin-12, or anti-interleukin-10. These
      results indicate that short-term culture with interferon-gamma and recombinant
      human interleukin-12 potently upregulates beta2 chain expression on T cells from
      normal volunteers, whereas a similar, but less marked effect occurs on T cells
      from Sezary syndrome patients and a low circulating tumor cell burden. In
      contrast, the beta2 chain appears to be suppressed on both CD4+ and CD8+ T cells
      from Sezary patients with a heavy circulating tumor cell burden and it is not
      induced by interferon-gamma or recombinant human interleukin-12. Therefore,
      recombinant human interleukin-12 is likely to be most effective for early stage
      cutaneous T cell lymphoma due to a greater display of beta2 receptors on
      responding CD8+ anti-tumor cytotoxic T cells.

PMID- 11442759
TI  - Mosaic pattern of maternal and paternal keratinocyte clones in normal human
      epidermis revealed by analysis of X-chromosome inactivation.
AB  - During early development of the female embryo, one X-chromosome is randomly
      inactivated in each cell. As a result of growth, migration, and differentiation,
      the adult female becomes a mosaic of cells with either the paternal or the
      maternal X-chromosome inactivated. It is not known what structure the X
      chromosome inactivation pattern has in skin of normal individuals. We
      investigated normal skin from four healthy females, heterozygous for the HUMARA
      microsatellite on the X-chromosome. Following careful microdissection, DNA from
      adjacent epidermal samples consisting of approximately 35 basal keratinocytes was
      digested with the methylation-sensitive enzyme HpaII. The inactivated X
      chromosome remained intact due to extensive methylation. The enzyme-digested DNA
      was amplified using polymerase chain reaction and fragments were analyzed for
      size. Through examination of adjacent samples and consecutive sections, we found
      normal human skin to be composed of a fine mosaic of tiles with either maternal
      or paternal X-chromosome inactivated. The sizes of these tiles were between 20
      and 350 basal cells. The method described has the potential to resolve the clonal
      status in normal as well as pathologic conditions.

PMID- 11442760
TI  - Interleukin-6-resistant melanoma cells exhibit reduced activation of STAT3 and
      lack of inhibition of cyclin E-associated kinase activity.
AB  - Development of cytokine resistance is an important feature of melanoma cells
      during tumor progression. To study the mechanisms of interleukin-6 resistance, we
      examined an interleukin-6 sensitive (WM35) and an interleukin-6 unresponsive cell
      line (WM9). Interleukin-6 treatment resulted in rapid inhibition of cyclin
      dependent kinase 2/cyclin E activity and accumulation of the hypophosphorylated
      retinoblastoma protein in WM35 but not in WM9 cells. In contrast to previous
      reports, no differences in the expression of the cyclin-dependent kinase 2
      inhibitor p21Cip1/WAF1 upon interleukin-6 treatment were found in both cell
      lines. Interleukin-6-induced inhibition of cyclin-dependent kinase 2 was also not
      due to changes in protein expression of cyclin-dependent kinase 2, cyclin E,
      p27Kip1 and cdc25A, a phosphatase positively regulating cyclin-dependent kinase 2
      activity. As it is established that interleukin-6 resistance of WM9 cells is not
      caused by differential interleukin-6 receptor expression, we studied whether this
      is due to defective interleukin-6 signaling in which activation of signal
      transducer and activator of transcription 3 is a critical step. WM9 cells showed
      reduced tyrosine phosphorylation, DNA binding, and delayed nuclear translocation
      of signal transducer and activator of transcription 3 as compared with WM35
      cells. The kinase upstream of signal transducer and activator of transcription 3,
      Janus kinase 1, was constitutively tyrosine-phosphorylated in WM9 cells and did
      not respond to interleukin-6 with increased phosphorylation. As compared with
      WM35 cells, interleukin-6 treatment of WM9 cells was not paralleled by reduced
      activity of the mitogen-activated protein kinase kinase-1, which suppresses
      activation of signal transducer and activator of transcription 3. Our data
      suggest that resistance of advanced melanoma cells to interleukin-6 is associated
      with reduced inhibition of cyclin-dependent kinase 2, which appears to be a
      consequence of a complex alteration in interleukin-6 signal transduction.

PMID- 11442761
TI  - Differential ultraviolet-B-induced immunomodulation in XPA, XPC, and CSB DNA
      repair-deficient mice.
AB  - Ultraviolet B irradiation has serious consequences for cellular immunity and can
      suppress the rejection of skin tumors and the resistance to infectious diseases.
      DNA damage plays a crucial role in these immunomodulatory effects of ultraviolet
      B, as impaired repair of ultraviolet-B-induced DNA damage has been shown to cause
      suppression of cellular immunity. Ultraviolet-B-induced DNA damage is repaired by
      the nucleotide excision repair mechanism very efficiently. Nucleotide excision
      repair comprises two subpathways: transcription-coupled and global genome repair.
      In this study the immunologic consequences of specific nucleotide excision repair
      defects in three mouse models, XPA, XPC, and CSB mutant mice, were investigated.
      XPA mice carry a total nucleotide excision repair defect, whereas XPC and CSB
      mice only lack global genome and transcription-coupled nucleotide excision
      repair, respectively. Our data demonstrate that cellular immune parameters in
      XPA, XPC, and CSB mice are normal compared with their wild-type (control)
      littermates. This may indicate that the reported altered cellular responses in
      xeroderma pigmentosum patients are not constitutive but could be due to external
      factors, such as ultraviolet B. Upon exposure to ultraviolet B, only XPA mice are
      very sensitive to ultraviolet-B-induced inhibition of Th1-mediated contact
      hypersensitivity responses and interferon-gamma production in skin draining lymph
      nodes. Lipopolysaccharide-stimulated tumor necrosis factor alpha and interleukin
      10 production are significantly augmented in both XPA and CSB mice after
      ultraviolet B exposure. Lymph node cell numbers were increased very significantly
      in XPA, mildly increased in CSB, and not in XPC mice. In general XPC mice do not
      exhibit any indication of enhanced ultraviolet B susceptibility with regard to
      the immune parameters analyzed. These data suggest that both global genome repair
      and transcription-coupled repair are needed to prevent immunomodulation by
      ultraviolet B, whereas transcription-coupled repair is the major DNA repair
      subpathway of nucleotide excision repair that prevents the acute ultraviolet-B
      induced effects such as erythema.

PMID- 11442762
TI  - Can increasing the viscosity of formulations be used to reduce the human skin
      penetration of the sunscreen oxybenzone?
AB  - The effect of adding thickening agents on the penetration of a sunscreen
      benzophenone-3 through epidermal and a high-density polyethylene membrane was
      studied using both very thick (infinite dose) and thin (in use) applications.
      Contradictory results were obtained. Thickening agents retard skin penetration,
      in a manner consistent with a diffusional resistance in the formulation, when
      applied as an infinite dose. In contrast, when applied as in thin (in use) doses,
      thickening agents promote penetration, most likely through greater stratum
      corneum diffusivity arising from an enhanced hydration by the thicker
      formulations. The two key implications from this work are (i) a recognition of
      the danger in the potential extrapolation of infinite dosing to in use
      situations, and (ii) to recognize that thicker formulations may sometimes enhance
      the penetration of other topical agents when applied "in use".

PMID- 11442763
TI  - Suppression of melanoma cell proliferation by histidine decarboxylase specific
      antisense oligonucleotides.
AB  - Histidine decarboxylase (HDC) is expressed by the cells of melanoma, in which the
      histamine content tends to be relatively high. This study shows that elevated
      expression of HDC was found by western blot analysis of primary and metastatic
      melanoma tissue using a polyclonal HDC specific antibody. The specificity of anti
      HDC antibody was confirmed by inhibition of HDC translation (i.e.,
      immunopositivity) in melanoma cells by HDC-specific antisense oligonucleotide.
      Moreover, the decrease in proliferation caused by HDC antisense oligonucleotides
      indicates considerable functional relevance of histamine synthesis in melanoma
      growth and suggests a possible in situ application of specific antisense
      oligonucleotides for HDC in melanoma therapy.

PMID- 11442764
TI  - L-ascorbic acid increases NFkappaB binding activity in UVA-irradiated HaCaT
      keratinocytes.

PMID- 11442765
TI  - The Pro162 variant is a loss-of-function mutation of the human melanocortin 1
      receptor gene.

PMID- 11442766
TI  - Melanosomal pH, pink locus protein and their roles in melanogenesis.

PMID- 11442767
TI  - A novel A(-4)-to-G acceptor splice site mutation leads to three bases insertion
      in ferrochelatase mRNA in a patient with erythropoietic protoporphyria.

PMID- 11442768
TI  - Mechanical stress induced by hyperosmolarity.

PMID- 11442770
TI  - Interferon-gamma production in skin during contact hypersensitivity. No
      contribution from keratinocytes.

PMID- 11442771
TI  - Differential and age-dependent effects of maternal deprivation on the
      hypothalamic-pituitary-adrenal axis of brown norway rats from youth to
      senescence.
AB  - In this study, the hypothesis was tested that infants deprived from maternal care
      show persistent changes in hypothalamic-pituitary-adrenal activity. For this
      purpose, we studied the effect of maternal deprivation in one cohort of the
      healthy ageing Brown Norway rat strain showing still more than 80% survival rate
      at 32 months of age. Three-day-old male Brown Norway rats were either maternally
      deprived for 24 h or remained with the dam. In 3, 12 and 30-32 months (young,
      adult, senescent) deprived rats and their nondeprived littermates (controls), we
      determined basal resting and stress-induced plasma adrenocorticotropic hormone
      (ACTH) and corticosterone as well as corticotropin releasing hormone (CRH) mRNA
      expression in the paraventricular nucleus (PVN) of the hypothalamus.
      Mineralocorticoid (MR) and glucocorticoid receptors (GR) in hippocampus and PVN
      were also assessed using in vitro cytosol binding and in situ hybridization. The
      effect of ageing per se showed that in the control nondeprived Brown Norway rats,
      basal corticosterone and ACTH concentrations did not change during life. However,
      with age, the corticosterone response to novelty stress became progressively
      attenuated, but prolonged, while there was an age-related increase in the ACTH
      response. CRH mRNA expression in PVN decreased with age. Hippocampal MR binding
      and MR mRNA expression in the dentate gyrus were reduced at senescence, as were
      the GR binding capacities in hippocampus and hypothalamus. Maternal deprivation
      did not affect survival rate, body weight, nor adrenal weight of the ageing Brown
      Norway rats. Basal corticosterone and ACTH levels were not affected by
      deprivation, except for a rise in basal corticosterone concentrations at 3
      months. At this age, the corticosterone output in response to novelty was
      attenuated in the deprived rats. In contrast, a striking surge in novelty stress
      induced corticosterone output occurred at midlife while, at senescence, the
      corticosterone and ACTH responses were attenuated again in the deprived animals,
      particularly after the more severe restraint stressor. CRH mRNA expression was
      reduced only during adulthood in the deprived animals. After maternal
      deprivation, the MR mRNA in dentate gyrus showed a transient midlife rise. GR
      binding in hypothalamus and hippocampus GR binding was reduced in young rats
      while, in the senescent deprived animals, a reduced GRmRNA expression was
      observed in PVN and hippocampal CA1. In conclusion, in the Brown Norway rat,
      ageing causes a progressive decline in corticosterone output after stress, which
      is paralleled at senescence by decreased MR and GR mRNA expression in hippocampus
      and hypothalamus. The long-term effects of maternal deprivation become manifest
      differently at different ages and depend on test conditions. The deprivation
      effect culminates in a midlife corticosterone surge and results at senescence in
      a strongly reduced corticosterone output.

PMID- 11442772
TI  - Serine/threonine phosphatase inhibitors decrease adrenergic arylalkylamine n
      acetyltransferase induction in the rat pineal gland.
AB  - Adrenergic regulation of the pineal enzyme serotonin N-acetyltransferase
      [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87] accounts for the
      circadian rhythm in melatonin formation. In the present study, the role of
      protein phosphatases in the adrenergic regulation of rat pineal AA-NAT was
      investigated using specific inhibitors. In cultured pineals, the serine/threonine
      phosphatase type 1 and type 2A inhibitors okadaic acid and calyculin A
      significantly decreased adrenergically or cAMP-induced AA-NAT activity, whereas
      the serine/threonine phosphatase type 2B inhibitor cypermethrin and tyrosine
      phosphatase inhibitor dephostatin were ineffective. Reverse transcriptase
      polymerase chain reaction (RT-PCR) data indicate that okadaic acid exerts its
      effect on cAMP-dependent AA-NAT induction by downregulating the amount of AA-NAT
      transcript. The 'third' messengers, inducible cAMP early repressor (ICER) and Fos
      related antigene-2 (Fra-2), are believed to play a negative role in pineal AA-NAT
      transcription. Okadaic acid increased the cAMP responsiveness of neither ICER
      mRNA nor Fra-2 mRNA. Therefore, the regulatory role of pineal serine/threonine
      phosphatases in adrenergically stimulated AA-NAT expression probably does not
      depend on ICER or Fra-2.

PMID- 11442773
TI  - Analysis of the post-translational processing of chromogranin A in rat
      neuroendocrine tissue employing an N-terminal site-specific antiserum.
AB  - Chromogranin A (CgA) is a complex prohormone expressed as a constituent of the
      regulated secretory pathway of numerous neuroendocrine cells. Recent
      investigations have demonstrated that CgA is selectively cleaved to generate
      distinct peptides in different neuroendocrine tissues. This investigation
      employed a site-specific antiserum that detects residues 98-106 rat CgA to
      examine the amino-terminal processing of CgA to generate beta-granin and related
      peptides in rat neuroendocrine tissues. Immunohistochemistry revealed moderate to
      intense beta-granin-like immunostaining in cells scattered throughout the
      anterior pituitary, thyroid, in the islets of Langerhans and in the mucosa of the
      gastrointestinal tract. Variable intensities of immunostaining were observed in
      distinct clusters of chromaffin cells. Quantitatively, the highest concentration
      of beta-granin-like immunoreactivity was detected in pituitary extracts.
      Significantly lower concentrations were detected in adrenal and thyroid glands,
      brain, ventral and dorsal pancreatic lobes and gastrointestinal tissue extracts.
      Chromatography resolved three distinct beta-granin-like immunoreactants; a large
      CgA-like form, an intermediate molecular form presumably corresponding to beta
      granin (rat CgA1-128) and small immunoreactants that coeluted with the synthetic
      peptide. Two beta-granin-like immunoreactants, 21 and 22 kDa, were detected
      following immunoblot analysis of pituitary extracts. This study has demonstrated
      that chromogranin A is subject to distinct amino-terminal patterns of tissue-and
      cell-specific processing to generate a beta-granin-like immunoreactant which is
      additionally cleaved in pancreatic, fundic and colonic tissue to generate
      previously unidentified peptides.

PMID- 11442774
TI  - Effect of nitric oxide synthase inhibition on fos expression in the hypothalamus
      of female rats following central oxytocin and systemic urethane administration.
AB  - Three experiments were carried out to investigate the pattern of neuronal
      activation induced by central oxytocin administration and its modulation by
      nitric oxide (NO). First, we compared the induction of Fos-like immunoreactivity
      (lir) in the supraoptic (SON) and paraventricular (PVN) nuclei and medial
      preoptic area (MPOA) after central oxytocin administration between nonlactating
      and lactating rats. Next, we investigated whether NO modulated Fos induction
      following central oxytocin administration using a nitric oxide synthase (NOS)
      inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Finally, to determine
      whether the effects of NOS inhibition on Fos induction would generalize to
      stimuli other than oxytocin, we compared Fos-lir in the SON and PVN of lactating
      and nonlactating rats following L-NAME and urethane administration. In the first
      two experiments, oxytocin (50 ng in 2 microl) or vehicle was administered into
      the third ventricle. L-NAME (50 mg/kg) was given by an intraperitoneal (i.p.)
      injection 30 min before oxytocin administration (experiment 2) or an i.p.
      injection of urethane (1.4 g/kg) (experiment 3). In all experiments, lactating
      rats were tested on day 12 or 13 postpartum and nonlactating females at least 11
      days after surgery or the start of the experiment. Central oxytocin infusion
      induced Fos expression in the SON and PVN in lactating and nonlactating rats and
      in the MPOA and bed nucleus of the stria terminalis in lactating rats. Overall,
      lactating rats that received L-NAME and oxytocin had a greater number of cells
      showing Fos-lir in both the SON and PVN. Conversely, L-NAME administration
      reduced Fos-lir in the SON and PVN in oxytocin-stimulated nonlactating rats. In
      urethane-treated rats, L-NAME administration did not change Fos-lir in lactating
      rats but reduced Fos-lir in nonlactating rats. These data suggest that the role
      of NO in modulating the activity of neurones in discrete nuclei in the
      hypothalamus varies across reproductive state and with the stimulus presented.

PMID- 11442775
TI  - The effect of acute and chronic restraint on the central expression of prepro
      neuropeptide Y mRNA in normotensive and hypertensive rats.
AB  - Neuropeptide Y (NPY), one of the most abundant neuropeptides found in the central
      nervous system (CNS), has been implicated in the regulation of many autonomic
      functions, including cardiovascular control and the central stress response. The
      present study represents a detailed investigation of the effects of acute and
      chronic restraint stress on the expression of the mRNA encoding the NPY
      precursor, prepro-NPY, in the CNS of normotensive Wistar-Kyoto (WKY) rats and
      spontaneously hypertensive rats (SHR) using in situ hybridization histochemistry.
      Basal (unstressed) levels of prepro-NPY mRNA expression were found to be
      significantly increased in the hypothalamic arcuate nucleus of SHR compared to
      WKY rats, with similar levels of prepro-NPY mRNA expression found in the
      remaining central nuclei. Following exposure to both acute and chronic restraint,
      significant changes in prepro-NPY mRNA expression were found in a variety of
      central regions in both strains, including the arcuate nucleus and hippocampus
      (both strains), medial amygdala and cortex (WKY only), and dentate gyrus, nucleus
      of the solitary tract and ventrolateral medulla (SHR only). A comparison of the
      temporal response to restraint revealed that significant differences between
      strains existed in regions such as the arcuate nucleus, hippocampus and dentate
      gyrus, providing further evidence that hypertensive rats apparently have an
      impaired neural stress response. The present study demonstrates that exposure to
      restraint results in significant changes in prepro-NPY mRNA expression in
      specific nuclei of both WKY and SHR that are components of not only the central
      circuitry regulating the stress response, but also the neural network modulating
      autonomic function.

PMID- 11442776
TI  - Tamoxifen diminishes methamphetamine-induced striatal dopamine depletion in
      intact female and male mice.
AB  - It has been demonstrated that the nigrostriatal dopaminergic system of male mice
      is more sensitive to the neurotoxic effects of methamphetamine (MA). The basis
      for this difference can be related to oestrogen, which has the capacity to
      function as a neuroprotectant against neurotoxins that target the nigrostriatal
      dopaminergic system. We examined the effects of the anti-oestrogen, tamoxifen
      (TMX), upon MA-induced neurotoxicity of the nigrostriatal dopaminergic system in
      intact female and male CD-1 mice. Striatal dopamine concentrations of TMX-treated
      female and male mice receiving MA were significantly greater than mice receiving
      MA alone. In female, but not male, mice, oestrogen treatment also resulted in
      greater striatal dopamine concentrations compared to mice receiving MA alone.
      Interestingly, male mice treated with oestrogen were particularly sensitive to
      the acute toxic effects of MA and displayed no evidence of nigrostriatal
      neuroprotection. The dihydroxyphenylacetic acid/dopamine ratios following MA for
      female and male mice treated with TMX or females treated with oestrogen were
      significantly reduced compared to MA-treated mice and oestrogen + MA-treated male
      mice. No differences among the treatment groups were obtained for dopamine in the
      hypothalamus or olfactory bulb. These data demonstrate that TMX treatment of
      intact female and male mice diminishes striatal dopamine depletions to the
      nigrostriatal dopaminergic neurotoxin, MA. Oestrogen also displayed this capacity
      when administered to female, but accentuated acute toxicity in male mice. These
      effects are relatively specific for the nigrostriatal dopaminergic system. Such
      data suggest that TMX can function as a nigrostriatal dopaminergic
      neuroprotectant against MA-induced neurotoxicity in intact female and male mice.

PMID- 11442777
TI  - Corticosterone exerts site-specific and state-dependent effects in prefrontal
      cortex and amygdala on regulation of adrenocorticotropic hormone, insulin and fat
      depots.
AB  - Chronic stress stimulates corticosterone secretion and recruits brain pathways
      that regulate energy balance (caloric acquisition and deposition) and facilitate
      hypothalamic-pituitary-adrenal responsiveness to new stressors. We implanted
      corticosterone or cholesterol bilaterally either near the central nucleus of the
      amygdala (CeA) or in the prefrontal cortex to determine whether high
      concentrations of the steroid act at either site, with or without chronic stress.
      Rats were adrenalectomized and treated systemically with low doses of
      corticosterone. Half were maintained at room temperature and the other half were
      exposed to 5 degrees C cold for 5 days before all rats were restrained. There was
      limited diffusion of corticosterone from brain implants. Corticosterone in
      prefrontal cortex, but not CeA, decreased plasma insulin and adrenocorticotropic
      hormone (ACTH) responses to acute restraint in both control and chronically cold
      stressed rats. Corticosterone implants near CeA decreased the weight of fat
      depots only in cold; corticosterone implants in prefrontal cortex were
      ineffective. We conclude that (i) corticosterone inhibits insulin and ACTH
      secretion by an action in prefrontal cortex but not CeA; (ii) high concentrations
      of corticosterone secreted during chronic stress alter metabolism through
      (autonomic) outputs of the CeA and prefrontal cortex in site- and variable
      specific fashion; and (iii) the amygdala is a component of a stress-recruited,
      state-dependent pathway.

PMID- 11442778
TI  - High voltage-activated Ca2+ currents in rat supraoptic neurones: biophysical
      properties and expression of the various channel alpha1 subunits.
AB  - The diversity of Ca2+ currents was studied in voltage-clamped acutely dissociated
      neurones from the rat supraoptic nucleus (SON), and the expression of the various
      corresponding pore-forming alpha1 subunits determined by immunohistochemistry. We
      observed the presence of all high voltage-activated L-, N-, P/Q- and R-type
      currents. We did not observe low-voltage-activated T-type current. The multimodal
      current/voltage relationships of L- and R-type currents indicated further
      heterogeneity within these current types, each exhibiting two components that
      differed by a high (-20 mV) and a lower (-40 mV) threshold potential of
      activation. L- and R-type currents were fast activating and showed time-dependent
      inactivation, conversely to N- and P/Q-type currents, which activated more slowly
      and did not inactivate. The immunocytochemical staining indicated that the soma
      and proximal dendrites of SON neurones were immunoreactive for Cav1.2, Cav1.3
      (forming L-type channels), Cav2.1 (P/Q-type), Cav2.2 (N-type) and Cav2.3 subunits
      (R-type). Each subunit exhibited further specificity in its distribution
      throughout the nucleus, and we particularly observed strong immunostaining of
      Cav1.3 and Cav2.3 subunits within the dendritic zone of the SON. These data show
      a high heterogeneity of Ca2+ channels in SON. neurones, both in their functional
      properties and cellular distribution. The lower threshold and rapidly activating
      L- and R-type currents should underlie major Ca2+ entry during action potentials,
      while the slower and higher threshold N- and P/Q-type currents should be
      preferentially recruited during burst activity. It will be of key interest to
      determine their respective role in the numerous Ca2+-dependent events that
      control the activity and physiology of SON neurones

PMID- 11442779
TI  - Antagonism of central vasopressin receptors blocks hypoglycemic stress induced
      inhibition of luteinizing hormone release in male rhesus macaques.
AB  - The first objective of this study was to investigate whether the inhibitory
      effect of insulin-induced hypoglycemia (IIH) on luteinizing hormone (LH)
      secretion was the same in unrestrained adult male rhesus macaques as has been
      previously reported in restrained female macaques. Since IIH did inhibit
      pulsatile LH secretion in adult male macaques, and some previous studies have
      implicated arginine vasopressin (AVP) as a central mediator of this inhibition,
      the second objective was to investigate whether antagonism of AVP action could
      reverse the IIH-induced inhibition of LH release in males. Ten adult male rhesus
      macaques (Macaca mulatta) were studied during 15-h periods (07.00-22.00 h), with
      blood samples collected every 15-min. There were three experimental groups;
      controls (n = 5), IIH (n = 6) and IIH plus vasopressin antagonist (AVPa; n = 6).
      During the hypoglycemia studies, the first 5 h served as a control for that
      occasion and an insulin bolus of 1 U/kg was administered intravenously at 12.00
      h. During the IIH plus AVPa, the vasopressin antagonist was infused intravenously
      from 12.00 h to 17.00 h. LH and testosterone decreased progressively after the
      insulin bolus in the IIH group reaching a minimum value at 4 h after the
      infusion. However, compared to the preinfusion levels, secretion of LH and
      testosterone was not suppressed by hypoglycemia in the group treated with the AVP
      antagonist. The present study shows that in male macaques not subjected to the
      psychological stress of restraint, IIH suppresses LH and testosterone secretion.
      This inhibition of LH release can be blocked in some animals by antagonism of
      central vasopressin receptors, suggesting that vasopressin is involved in the
      suppression of gonadotropin releasing hormone/LH release induced by hypoglycemia.

PMID- 11442780
TI  - Pharmacokinetic terms: symbols and units.

PMID- 11442781
TI  - Depletion study of trimethoprim and sulphadiazine in milk and its relationship
      with mastitis pathogenic bacteria strains minimum inhibitory concentrations
      (MICs) in dairy cows.
AB  - Time-related concentrations in milk of a combination of trimethoprim
      sulphadiazine (TMP-SDZ) intramammary formulated infusion and its relationship
      with pathogenic bacteria strains minimum inhibitory concentrations (MICs)
      isolated from clinical mastitis cows were analysed. The MICs study was performed
      for Escherichia coli, Staphylococcus aureus and Streptococcus sp. strains. The
      SDZ concentrations in milk were analysed using high-performance liquid
      chromatography (HPLC) and TMP using a microbiological assay. Ten lactating cows
      milked three times daily were used in the time-concentration studies of TMP-SDZ.
      Milk samples (approximately 20 mL) from the treated mammary quarters were taken
      at 6, 12, 24, 30 and 36 h after first administration. In order to define the
      withdrawal time, milk samples from the treated mammary quarters were taken at 24,
      36, 48, 72, 84 and 96 h, after finishing the therapy. The MICs fluctuated between
      1 and 8 microg/mL. Effective therapeutic concentrations lasted for 36 h when
      intramammary infusion was repeated three times every 12 h. No TMP was detected in
      milk for 24 h after finishing therapy. Milk SDZ concentrations were below 0.1
      microg/mL in all treated cows after 84 h finishing therapy. At 96 h after
      finishing therapy, no SDZ milk concentrations were found in six animals, although
      four animals of the experimental group still had concentrations of 0.07
      microg/mL.

PMID- 11442782
TI  - Ropivacaine in the horse: its pharmacological responses, urinary detection and
      mass spectral confirmation.
AB  - This report evaluates the pharmacological responses, urinary detection and mass
      spectral confirmation of ropivacaine in horses. Ropivacaine, a potent local
      anesthetic (LA) recently introduced in human medicine, has an estimated highest
      no-effect dose (HNED) of about 0.4 mg/site as determined in our abaxial sesamoid
      block model. Apparent ropivacaine equivalents were detectable by ELISA screening
      using a mepivacaine ELISA test after administration of clinically effective
      doses. Mass spectral examination of postadministration urine samples showed no
      detectable parent ropivacaine, but a compound indistinguishable from authentic 3
      hydroxyropivacaine was recovered from these samples. The study shows that
      ropivacaine is a potent LA in the horse, that clinically effective doses can be
      detected in postadministration samples by ELISA-based screening, and that its
      major post administration urinary metabolite is 3-hydroxyropivacaine.

PMID- 11442783
TI  - Pharmacokinetics of moxidectin and ivermectin following intravenous injection in
      pigs with different body compositions.
AB  - Macrocyclic lactones (ML) are highly effective anthelmintics that provide a long
      protective period after administration because of their extensive distribution
      into fat. This study examined whether the body composition of the animal at the
      time of treatment had any influence on the pharmacokinetics of two MLs,
      moxidectin (MOX) and ivermectin (IVM). 'Fat' and 'lean' lines of pigs were
      established using two different diets, with weekly determination of liveweight
      and backfat thickness confirming the difference in body condition between the
      groups. Blood samples were taken at regular intervals following i.v. injection of
      IVM or MOX at a dose of 300 microg/kg and the plasma was analysed using
      fluorescence high performance liquid chromatography (HPLC) to determine the
      concentration of IVM or MOX in the samples. Regardless of body composition IVM
      and MOX kinetics were very different with MOX having a greater apparent volume of
      distribution, longer distribution and elimination half-lives and a slower
      clearance rate than IVM, which led to MOX being detectable in plasma for >40 days
      compared with only 8-10 days for IVM. Altering body composition had no detectable
      influence on the kinetic disposition of IVM in this study. In contrast, although
      there was no difference in AUC or the volume of distribution, MOX was distributed
      within and eliminated from the lean animals more rapidly than from the fat
      animals.

PMID- 11442784
TI  - The oral bioavailability of ibuprofen enantiomers in broiler chickens.
AB  - Doses of racemic ibuprofen ranging from 5 to 20 mg/kg body weight were
      administered intravenously (i.v.) and orally to broiler chickens and plasma
      concentration-time profiles for both ibuprofen enantiomers were determined. The
      absorption of ibuprofen was evaluated after a bolus administration of a
      commercially available suspension into the crop and proventriculus, respectively.
      An enterohepatic circulation as described for other nonsteroidal anti
      inflammatory drugs (NSAIDs) in other species could be suggested for both
      enantiomers after i.v. and oral administration. Significantly higher area under
      the curve (AUC) values for S(+)-ibuprofen compared with R(-)-ibuprofen were
      collected after crop and proventriculus administration. Several factors could be
      responsible for the significant differences in AUC values between both
      enantiomers.

PMID- 11442785
TI  - Absorption, tissue distribution and excretion of flumequine and oxolinic acid in
      corkwing wrasse (Symphodus melops) following a single intraperitoneal injection
      or bath treatment.
AB  - The pharmacokinetic properties of the antibacterial agents oxolinic acid and
      flumequine were studied in corkwing wrasse (Symphodus melops) after either
      intraperitoneal injection or bath treatment. Following intraperitoneal
      administration the peak plasma concentrations (Cmax) and the time to peak plasma
      concentrations (Tmax) were estimated to be 2.0 microg/mL and 12 h, respectively,
      for oxolinic acid and 2.6 microg/mL and 12 h, respectively, for flumequine. In
      muscle, Cmax and Tmax were estimated to 6.7 microg/g and 12 h, respectively, for
      oxolinic acid with corresponding values of 8.5 microg/g and 13 h, respectively,
      for flumequine. In liver, Cmax and Tmax were calculated to 7.0 microg/g and 12 h,
      respectively, for oxolinic and 12.2 microg/g and 11 h, respectively, for
      flumequine. Elimination half-lives (t1/2 beta) of 26, 24 and 29 h, respectively,
      for plasma, muscle and liver were calculated for flumequine. For oxolinic acid
      two distinct elimination phases were found and calculated to be 16 h (t1/2 beta)
      and 57 h (t1/2 gamma) in plasma, 15 and 59 h, respectively, in muscle and 20 and
      72 h, respectively, in liver. Bath treatment using 150 mg/L of flumequine or 200
      mg/L of oxolinic acid for 72 h resulted in flumequine concentrations of 1.0
      microg/mL in plasma, 5.0 microg/g in muscle and 12.4 microg/g in liver.
      Corresponding values for oxolinic acid were 1.0 microg/g in plasma, 2.5 microg/g
      in muscle and 4.9 microg/g in liver.

PMID- 11442786
TI  - Albendazole sulphoxide enantiomeric ratios in plasma and target tissues after
      intravenous administration of ricobendazole to cattle.
AB  - The comparative concentration profiles of the (+) and (-) albendazole sulphoxide
      (ABZSO) enantiomers obtained in plasma and in selected target tissues/fluids
      after intravenous (i.v.) administration of a racemic formulation of ricobendazole
      (RBZ) to cattle were characterised. Fourteen Holstein calves received RBZ
      (racemic solution, 150 mg/mL) by i.v. administration at 7.5 mg/kg. Jugular blood
      samples were collected over 48 h post-treatment (plasma kinetic trial) and two
      animals were sacrificed at either 4, 12, 20, 28 or 32 h post-treatment to obtain
      samples of abomasal/small intestine mucosal tissue, abomasal/small intestine
      fluids, bile, liver and lung tissue (tissue distribution study). The (-)ABZSO
      enantiomer was depleted significantly faster from plasma compared with the
      (+)ABZSO antipode. The plasma AUC for (+)ABZSO (38.3 microg. h/mL) was
      significantly higher (P < 0.05) compared with that obtained for (-)ABZSO (20.5
      microg. h/mL). The (+)ABZSO enantiomer was the predominant antipode measured in
      bile, abomasal fluid and abomasal mucosa. For instance, at 12 h post-treatment
      the (+)/(-) concentration ratios were: 12.9 (plasma), 1.62 (abomasal mucosa),
      13.0 (abomasal fluid), 2.92 (intestinal mucosa), 9.87 (intestinal fluid) and 21.5
      (bile). No marked differences between the concentration profiles of both
      enantiomers were observed in the liver tissue. Albendazole (ABZ) was recovered
      from the liver, lung and gastrointestinal (GI) mucosal tissues of RBZ-treated
      calves up to 32 h post-treatment, probably produced by a GI microflora-mediated
      sulphoreduction of RBZ. An enantioselective kinetic behaviour may account both
      for the faster depletion of the (-) enantiomer and for the higher availabilities
      of the (+) antipode observed in plasma and in most of the tissues/fluids
      investigated. The simultaneous evaluation of the plasma kinetics and tissue
      concentration profiles of both enantiomeric forms reported here, may help to
      interpret the relationship between chiral behaviour and pharmacological action
      for sulphoxide derivatives of benzimidazole (BZD) methylcarbamate anthelmintics.

PMID- 11442787
TI  - Feasibility of interspecies extrapolation in determining the bioequivalence of
      animal products intended for intramuscular administration.
AB  - To examine the validity of extrapolating parenteral product bioequivalence
      determinations across target animal species, the relative bioavailability of two
      injectable formulations of ampicillin trihydrate (PolyflexR, a water-based
      suspension, and Ampi-kel 10R, an oil-based suspension) was examined in calves,
      sheep and swine. Employing products recognized to be bioinequivalent provided an
      opportunity to explore potential species-by-formulation interactions. As compared
      with PolyflexR, Ampi-kel 10R exhibited lower area under the curve (AUC) estimates
      but higher peak concentrations in all target animal species. Nevertheless, marked
      interspecies differences were noted in the width and bounds of the confidence
      intervals about the differences in treatment means. Potential physiological and
      physico-chemical reasons for these findings are discussed.

PMID- 11442788
TI  - Pharmacokinetics of amikacin after single intravenous and intramuscular
      administration in calves.

PMID- 11442789
TI  - The ATCvet classification system for veterinary medicinal products.

PMID- 11442790
TI  - Pharmacokinetics of intravenous imipramine hydrochloride in cattle.

PMID- 11442791
TI  - GC-MS characterization of urinary metabolites and changes of ethisterone and
      testosterone profile after oral administration of danazol in equine.

PMID- 11442792
TI  - The disposition of marbofloxacin in Eurasian buzzards (Buteo buteo) after
      intravenous administration.

PMID- 11442793
TI  - Bioavailability and disposition of sodium and procaine penicillin G
      (benzylpenicillin) administered orally with milk to calves.
AB  - Eighteen 1-week-old Holstein calves were randomly assigned to one of three
      groups: (a) sodium penicillin G administered intravenously, (b) sodium penicillin
      G administered orally, or (c) procaine penicillin G administered orally. All
      calves were dosed with penicillin G at 4.0 mg/kg BW. At 5 weeks of age, the
      calves were dosed again. Blood samples were taken serially for 24 h after both
      dosings. Plasma was assayed for penicillin G by high performance liquid
      chromatography (HPLC). For i.v. administration, the area under the concentration
      time curve (AUC), 7456 and 5508 ng/mL h, and systemic clearance, 0.54 and 0.73
      L/kg h, were significantly different (P < 0.05) at 1 and 5 weeks of age,
      respectively. There were no significant differences between orally administered
      sodium and procaine penicillin G within the same age groups. Following oral
      (p.o.) administration, there were significant differences (P < 0.01) at 1 and 5
      weeks of age in the AUC, 760 and 409 ng/mL h, terminal half-life, 2.1 and 1.6 h,
      time of maximum concentration (TMAX), 3.0 and 2.3 h, and maximum plasma
      concentration (CMAX), 85 and 58 ng/mL, respectively. Bioavailability was 10.2 and
      7.4% at 1 and 5 weeks, respectively.

PMID- 11442794
TI  - Influence of verapamil on the efflux and metabolism of 14C moxidectin in cultured
      rat hepatocytes.
AB  - Moxidectin (MOX) is an antiparasitic drug widely used in cattle, sheep and
      companion animals. As a result of the implication of cytochrome P450 3 A in the
      metabolism of MOX and the role of competitor substrates of P-glycoprotein (Pgp)
      in modification of the bioavailability of endectocides, we studied the influence
      of verapamil (a multidrug-resistance reversing agent) on the metabolism of 14C
      moxidectin in cultured rat hepatocytes over 72 h. The metabolism of MOX remained
      low: 10.79 +/- 1.99% of the total 14C moxidectin for the main detected metabolite
      in verapamil-treated cells and 7.17 +/- 0.74% for the control cells after 24 h.
      The main detected metabolite in rat hepatocytes was the same as that detected in
      rat hepatic microsomes (the C29 monohydroxymethyl metabolite). Verapamil
      increased the quantity of MOX in the cells after 24, 48 and 72 h. Examination of
      the Area Under the concentration time Curve (AUC) of the main detected metabolite
      revealed a significant increase in the exposure of cells to MOX after verapamil
      treatment throughout the experiment. It is hypothesized that verapamil interfered
      with MOX as a substrate for Pgp during the initial incubation period. After this
      initial interaction, verapamil metabolites were able to interfere with Pgp. This
      experiment demonstrated the implication of Pgp in the transport of MOX and
      allowed prediction of the drug-drug interactions which might modify the
      bioavailability of endectocides.

PMID- 11442795
TI  - Enantiospecific pharmacokinetics of ketoprofen in plasma and synovial fluid of
      horses with acute synovitis.
AB  - Pharmacokinetic parameters were established for enantiomers of the nonsteroidal
      anti-inflammatory drug (NSAID) ketoprofen (KTP) administered as the racemic
      mixture at a dose of 2.2 mg/kg and as separate enantiomers, each at a dose of 1.1
      mg/kg to a group of six horses (five mares and one gelding). A four-period cross
      over study in a LPS-induced model of acute synovitis was used. After
      administration of the racemic mixture S(+)KTP was the predominant enantiomer in
      plasma as well as in synovial fluid. Unidirectional inversion of R(-) to S(+)KTP
      was demonstrated but the inversion was less marked than previously reported. It
      is suggested that this reduction could be because of the influence of the
      inflammatory reaction on hepatic metabolism. The disposition of KTP enantiomers
      after administration of the racemic mixture was similar to those observed after
      administration of S(+) and R(-)KTP. The S(+) and R(-)KTP concentrations in
      synovial fluid were low and short lasting. After administration of R(-)KTP
      significant concentrations of the optical antipode were detected in synovial
      fluid.

PMID- 11442796
TI  - Comparison of cefepime pharmacokinetics in neonatal foals and adult dogs.
AB  - The pharmacokinetics of cefepime, a new fourth generation cephalosporin with
      enhanced antibacterial activity, was examined in neonatal foals and adult dogs.
      Cefepime was administered intravenously (i.v.) at a dose of 14 mg/kg to five
      neonatal foals and six adult dogs. Blood samples were collected in both groups of
      animals and plasma cefepime concentrations measured by reverse-phase high
      performance liquid chromatography (HPLC). Cefepime concentrations in both groups
      of animals were described by a two-compartment pharmacokinetic model with
      elimination half-lives of 1.65 and 1.09 h for the foal and dog, respectively. We
      tested whether or not pharmacokinetic parameters for cefepime could be scaled
      across species using principles of allometry. The parameters of elimination half
      life (t(1/2)beta), apparent volume of distribution (VDarea), and systemic
      clearance (CL) were scaled linearly to body weight on a double logarithmic plot
      with allometric exponents for body weight of 0.26, 1.08 and 0.72, respectively.
      This study further determined doses for cefepime, a potentially useful antibiotic
      for neonatal foals and dogs, from the pharmacokinetic values. An i.v. dose of
      cefepime estimated from this study for treating sensitive bacteria was 11 mg/kg
      every 8 h for neonatal foals and 40 mg/kg every 6 h for dogs.

PMID- 11442797
TI  - Allometric analysis of thiamphenicol disposition among seven mammalian species.
AB  - The pharmacokinetics of thiamphenicol (TAP), a broad-spectrum antibiotic, was
      determined in male mice, rats, rabbits, dogs, pigs, sheep and calves. The
      relationship between the main pharmacokinetic parameters of TAP and body weight
      (W) was studied across these seven mammalian species, using double-logarithmic
      plots. The experimental values of volume of distribution (Vss), clearance (Cl)
      and elimination half-life (t(1/2)beta) were plotted, and extrapolated values were
      determined from corresponding allometric equations. These parameters were fitted
      to the following equations: Vss=0.98W0.92, Cl=15.80W0.76 and
      t(1/2)beta=0.94W0.20, and present good correlation (Vss: r2=0.997, P < 0.001; Cl:
      r2=0.976, P < 0.001, t(1/2)beta: r2=0.852, P < 0.005), that is expected of a drug
      eliminated primarily by renal glomerular filtration, with insignificant hepatic
      metabolism. For the t(1/2)beta, the extrapolated and observed values were
      similar. The extrapolated values of Cl were close to the experimental values,
      except for the mouse and pig mean percent error [(M.E.) equal to 62 and 119%,
      respectively], while the extrapolated and observed values for the Vss were very
      similar. The comparison between experimental and extrapolated values suggests
      that it could be possible to extrapolate, with good prediction, the kinetic
      parameters of this drug for mammalian species, using allometric scaling, except
      for the species that eliminate the drug by a combination of renal excretion and
      hepatic metabolism.

PMID- 11442798
TI  - Pharmacokinetics of ricobendazole in calves.
AB  - The pharmacokinetics of ricobendazole (RBZ) and its major metabolite albendazole
      sulphone (ABZSO2) were studied in six calves, after administration of RBZ (7.5
      mg/kg), using a 10% experimental solution by the intravenous (i.v.) route, a 10%
      commercial solution by the subcutaneous (s.c.) route, and a 10% experimental
      suspension by the intraruminal (i.r.) route. Blood samples were drawn during a 60
      h period. Plasma drug and metabolite concentrations were determined by HPLC. The
      pharmacokinetic evaluation in each case was prepared by weighted least-squares
      nonlinear regression analysis. Ricobendazole i.v. data were best fitted by a two
      compartment model. The best pharmacokinetic exponents and coefficients were
      estimated, and the pharmacokinetic variables for RBZ and ABZSO2 were calculated
      from them. Similar patterns of plasma disposition were found for RBZ after i.r.
      and s.c. administration, suggesting delayed release from the s.c. site resembling
      the slow release of the drug from the rumen.

PMID- 11442799
TI  - Endothelin receptor mediating contraction of isolated bovine coronary artery.
AB  - We studied endothelin (ET) receptors and their subtypes on isolated bovine
      coronary arteries. Endothelin receptors that mediated contraction of isolated
      bovine coronary artery were characterized by the use of antagonists and agonists.
      Contractions induced by the nonselective agonist ET-1 (10-10-10-7 M) were not
      affected by the removal of the endothelium (pEC50: 8.52, maximal contraction:
      105% of that induced by 60 mM KCl). BQ-123 (3 x 10-7 M) antagonized contractions
      of endothelium-denuded coronary rings induced by low concentrations of ET-1 (10
      10 or 10-9 M), but potentiated the contractions induced by higher concentrations
      of ET-1 (3 x 10-8 and 10-7 M). BQ-788 (10-6 M) potentiated contractions induced
      by ET-1 (3 x 10-10 and 10-7 M). In the presence of BQ-788 (10-6 M), BQ-123 (3 x
      10-8-3 x 10-6 M) concentration - dependently inhibited contractions induced by ET
      1 (3 x 10-10 and 10-7 M) (pA2: 6.61). Sarafotoxin S6b (10-9-3 x 10-7 M) evoked
      contractions in the denuded coronary artery (pEC50: 8.49, maximal contraction:
      139% of 60 mM KCl). The BQ-123 caused a concentration-dependent rightward shift
      of contractions induced by sarafotoxin S6b (pA2: 7.89). The present study
      indicates that ET-1 and sarafotoxin S6b contract the isolated bovine coronary
      artery by stimulating ETA receptors on smooth muscle cells, and that ETB
      receptors might suppress the ET-1-induced contractions.

PMID- 11442800
TI  - Inflammatory mediators induce endothelium-dependent adherence of equine
      eosinophils to cultured endothelial cells.
AB  - Accumulation of equine eosinophils at sites of parasite infestation or allergic
      inflammation depends upon their adherence to vascular endothelial cells and
      subsequent migration through the endothelium and extracellular matrix. This study
      has examined whether cytokines, which cause endothelial cell-dependent eosinophil
      adherence in other species, and histamine and substance P, which increase
      adherence of equine eosinophils to protein coated plastic, induce equine
      eosinophil adherence to cultured equine digital vein endothelial cell (EDVEC)
      monolayers. The EDVEC monolayers were stimulated with recombinant human (rh)
      interleukin (IL)-1beta, rhTNFalpha, substance P or histamine for different times
      and with a range of concentrations of mediators and the adherence of blood
      eosinophils from normal horses examined. All four mediators caused time- and
      concentration-dependent increases in adherence. However, neither the response to
      substance P, nor that to histamine, reached a maximum at the highest
      concentration tested (10-3 M: 10.6 +/- 2.6% and 4.5 +/- 0.6% adherent cells vs.
      background adherence of 1.9 +/- 0.4% and 1.1 +/- 0.2%; values for substance P and
      histamine, respectively, expressed as a percentage of total cells added
      initially; n=4). These data suggest that, as in other species, cytokines induce
      endothelial cell-dependent eosinophil adherence and mediators released during
      allergic inflammation may play a role in eosinophil recruitment by this
      mechanism.

PMID- 11442801
TI  - Effects of 8-epi-PGF2alpha on isolated bronchial smooth muscle of healthy and
      heaves-affected horses.
AB  - 8-Epi-PGF2alpha, a prostaglandin-like compound generated by oxidative stress, has
      been shown to be an in vitro bronchoconstrictor in airways from healthy
      laboratory animals and healthy humans, but it has never been studied in diseased
      airways. Here, the bronchoconstrictive capacity of 8-epi-PGF2alpha on isolated
      bronchial rings (BR) of healthy and heaves-affected horses was evaluated by
      comparing the maximal effect and the potency of 8-epi-PGF2alpha to those of (1)
      acetylcholine (ACh), (2) its stereoisomer PGF2alpha and (3) its synthetic
      receptor agonist, U46619. Furthermore, the potential capacity of 8-epi-PGF2alpha
      to enhance the cholinergic (ACh) responsiveness of bronchial smooth muscle was
      investigated. 8-Epi-PGF2alpha contracted BR with a rank order of efficacy of Ach
      > U44619 > PGF2alpha > 8-epi-PGF2alpha in both healthy and heaves-affected
      horses. The contractile maximal response elicited by 8-epi-PGF2alpha was
      significantly smaller than that elicited by the other drugs, but was
      significantly higher in BR from heaves-affected horses than in those sampled in
      healthy horses, whilst pD2 values were similar. A subthreshold concentration of 8
      epi-PGF2alpha (10-7 M) did not induce in vitro cholinergic hyper-responsiveness
      in BR of either healthy or heaves-affected horses. In conclusion, it has been
      demonstrated that 8-epi-PGF2alpha is an in vitro bronchoconstrictor of minor
      importance in healthy horses, but whose efficacy is significantly increased in
      heaves-affected horses.

PMID- 11442802
TI  - Stereoselective pharmacokinetics of ketoprofen in llamas following intravenous
      administration.

PMID- 11442803
TI  - Pharmacokinetics of phenylbutazone in llamas following single intravenous and
      oral doses.

PMID- 11442804
TI  - Concentration-dependent inhibition of sheep erythrocyte ghost plasma membrane
      Ca2+-ATPase activity by Berenil.

PMID- 11442805
TI  - Pharmacokinetics and side-effects of gentamicin in healthy and pseudomonas
      aeruginosa infected sheep.

PMID- 11442806
TI  - A coelectroporation method for the isolation of cryptic plasmids from Lactococcus
      lactis.
AB  - AIMS: A coelectroporation method using a marker plasmid for indirect selection of
      lactococcal plasmids with unassigned functions was evaluated. METHODS AND
      RESULTS: Cryptic plasmids were mixed with an erythromycin resistance (Eryr)
      marker plasmid and introduced into a recipient strain by electroporation,
      followed by plasmid extraction of erythromycin-resistant transformants. By
      optimizing the ratio between the marker plasmid and the cryptic plasmids, an
      average of 20% cotransformants was obtained, including combinations of more than
      one cryptic plasmid. The marker plasmid pSA3 was easily eliminated from the
      cotransformed cells by subculture without selective pressure. CONCLUSION: This
      cotransformation approach reduces the number of colonies that must be screened to
      find transformants harbouring cryptic plasmids. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The method facilitates the isolation of cryptic plasmids, helps in
      assigning functions to unknown plasmids and allows construction of food-grade
      lactococcal strains with new combinations of wild-type plasmids.

PMID- 11442807
TI  - Optimization of carotenoid production from hyper-producing Rhodotorula glutinis
      mutant 32 by a factorial approach.
AB  - AIMS: Optimization of carotenoid production by a mutant of Rhodotorula glutinis.
      METHODS: The growth and carotenoid production was optimized in shake flasks using
      a two-level, three-variable factorial design. RESULTS: The volumetric carotenoid
      production could be increased to 129 +/- 2 mg x 1(-1) in a medium containing (g x
      l(-1)) yeast extract 11.74, glucose 46 and threonine 18 along with other
      micronutrients, wherein, beta-carotene yield was 102 +/- 2 mg x l(-1), accounting
      for 80% of the total carotenoids. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      medium optimization resulted in a fourfold increase in volumetric production and
      a twofold increase in the cellular accumulation of carotenoids. In view of such
      high yields, the mutant of Rhodotorula glutinis can be a potential source of beta
      carotene.

PMID- 11442808
TI  - A microwave-based method for nucleic acid isolation from environmental samples.
AB  - AIMS: A simple and rapid method was described for DNA isolation directly from
      activated sludge or other environmental sources, including soil and sediments.
      METHODS AND RESULTS: The present method is based on microwave thermal shock and
      provides DNA suitable for further analysis. It is also effective for RNA
      extraction. CONCLUSION: The protocol is effective, easy, fast and does not
      require the use of expensive equipment or reagents. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The described method can be applied to difficult substrates in
      environmental microbiology studies.

PMID- 11442809
TI  - Biodecolorization screening of synthetic dyes by four white-rot fungi in a solid
      medium: possible role of siderophores.
AB  - AIMS: Four selected fungi were screened for their ability to decolourize a
      textile effluent and commercial reactive dyes in a solid medium. METHODS AND
      RESULTS: Ligninolytic enzymes activities (lignin peroxidase, manganese peroxidase
      and laccase) and siderophores presence were monitored in decolourized plates.
      RESULTS: The results showed low lignin peroxidase activity and no manganese
      peroxidase activity was detected for all fungi. Laccase activity was observed in
      Reactive Blue 19 decolourized plates by Trametes versicolor and Trametes villosa.
      Siderophores presence was observed in Trametes versicolor, Phanerochaete
      chrysosporium and Lentinus edodes decolourized plates. CONCLUSION: Lentinus
      edodes displayed the greatest decolourization ability both in terms of extent and
      rapidity of decolourization. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      transformation observed for dyes open the possibility to study siderophores to
      treat dyes and textile effluents.

PMID- 11442810
TI  - RAPD-PCR characterization of lactobacilli isolated from artisanal meat plants and
      traditional fermented sausages of Veneto region (Italy).
AB  - AIMS: The study was carried out to evaluate the use of randomly amplified
      polymorphic DNA-polymerase chain reaction (RAPD-PCR) as a method for the
      identification of lactobacilli isolated from meat products. METHODS AND RESULTS:
      RAPD-PCR with primers M13 and D8635 was applied to the identification and
      intraspecific differentiation of 53 lactobacilli isolates originating from
      traditional fermented sausages and artisanal meat plants of the Veneto region
      (Italy). Most of the isolates were assigned to the species Lactobacillus sakei
      and Lact. curvatus; differentiation of groups of strains within the species was
      also possible. CONCLUSION: RAPD-PCR could be applied to the identification of
      lactobacilli species most commonly found in meat products. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The method, which is easy and rapid to perform, could be
      useful for the study of the lactobacilli populations present in fermented
      sausages, and could help in the selection of candidate strains to use as starter
      cultures in meat fermentation.

PMID- 11442811
TI  - Development of a rapid method for the detection of verocytotoxin-producing
      Escherichia coli (VTEC).
AB  - AIMS: The object of this study was to adapt a new test kit to achieve the rapid
      identification of verocytotoxin-producing Escherichia coli (VTEC). METHODS AND
      RESULTS: The kit, which is based on reversed passive latex agglutination (RPLA),
      was combined with a method for identifying heat-labile enterotoxin-producing E.
      coli (LT-ETEC). An answer can thereby be obtained within a single working day.
      Over 200 strains, both VTEC and non-VTEC, of human and animal origin, belonging
      to a variety of serotypes were tested in this new rapid technique. Apart from
      three false-positive results, all other strains gave the correct answer by this
      rapid method. CONCLUSION: The method should enable the diagnosis of these
      important human pathogens to be made rapidly by most microbiological
      laboratories, and permit appropriate actions to be taken rapidly and therefore
      more effectively.

PMID- 11442812
TI  - Immunomagnetic separation of Escherichia coli O26, O111 and O157 from vegetables.
AB  - AIMS: Raw fruits and vegetables have been increasingly associated with human
      infections caused by Shiga toxin-producing Escherichia coli. This study evaluates
      the isolation and detection of E. coli O26, O111 and O157 from vegetable samples
      using immunomagnetic particles. METHODS AND RESULTS: Standard cultivation and
      immunomagnetic separation (IMS) procedures were compared. It was found that
      immunomagnetic particles could efficiently concentrate E. coli cells, detecting
      significantly more bacteria than with standard cultivation procedures.
      CONCLUSION: Bacteria were detected in 93-100% of the inoculated samples using the
      IMS procedure, but only 36-93% samples tested by standard cultivation procedures
      were found to be positive. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
      indicate that E. coli O26, O111 and O157 immunomagnetic particles can be a very
      useful and efficient tool for the detection of E. coli strains in raw vegetables,
      and could probably be used with samples of animal origin.

PMID- 11442813
TI  - Production of asporogenous mutants of Bacillus sphaericus 2362 in continuous
      culture.
AB  - AIMS: To report the production of asporogenous mutants (Spo-) of Bacillus
      sphaericus 2362 in continuous culture. METHODS AND RESULTS: Microbial culture
      samples were taken at 0.05 h-1 dilution rate and plated out on nutrient agar
      plates. Translucent colonies were obtained with vegetative morphology under phase
      contrast microscope. Heat resistance evaluations at different temperature
      settings showed that the Spo- mutants had lower heat resistance than the Spo+
      wild type. Western blots analyses carried out on both wild type and the mutants
      indicated the presence of binary protein toxins of 42 and 51 kDa in both.
      Bioassays carried out on the wild type and the Spo- mutants against mosquitoes
      showed the mutants to be 100-fold less toxic in comparison to the wild type.
      CONCLUSION: Existence and production of asporogenous mutants of Bacillus
      sphaericus 2362 in continuous culture at low dilution rates is demonstrated by
      this study. The organism's ability to produce toxins appears to be significantly
      reduced by the mutational process. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      production of asporogenous mutants had not been reported previously among strains
      of Bacillus sphaericus. The present report on the toxigenic capability of
      asporogenous mutants also raises the possibility of using continuous culture to
      significantly improve the productivity of toxin production in future.

PMID- 11442814
TI  - Detection of extracellular bound proteinase in EPS-producing lactic acid bacteria
      cultures on skim milk agar.
AB  - AIMS: Skim milk agar was developed to investigate extracellular cell-bound
      proteinase in yogurt cultures, Streptococcus thermophilus and Lactobacillus
      bulgaricus. METHODS AND RESULTS: The Lact. bulgaricus cultures produced more
      extracellular cell-bound proteinase than did Strep. thermophilus cultures. Strong
      positive correlations between the size of the exopolysaccharide (EPS) layer and
      extracellular cell-bound proteinase were found for both Streptococcus and
      Lactobacillus cultures. CONCLUSION: Strong positive linear relationships existed
      between the EPS size and colony size and the diameter of clear zone and colony
      size for Streptococcus cultures, whereas weak positive linear relationships were
      observed for Lactobacillus cultures. SIGNIFICANCE AND IMPACT OF THE STUDY: These
      data are useful to validate the relationship between extracellular proteinase and
      the EPS size of LAB. Also, a convenient medium to detect the presence of
      extracellular cell-bound proteinase of LAB is valuable for dairy industries.

PMID- 11442815
TI  - Effect of trans-2-hexenal on the growth of Aspergillus flavus in relation to its
      concentration, temperature and water activity.
AB  - AIMS: The antifungal activity of trans-2-hexenal on Aspergillus flavus in a model
      system in relation to its concentration, incubation temperature and aw was
      assessed. METHODS AND RESULTS: A model describing the antifungal activity of the
      aldehyde in relation to these variables was obtained. CONCLUSION: According to
      this model, the inhibition of A. flavus was weakly dependent on the incubation
      temperature (at least within the range of values considered) and strongly
      affected by the trans-2-hexenal concentration and aw, which showed a remarkable
      synergistic effect. SIGNIFICANCE AND IMPACT OF THE STUDY: Trans-2-hexenal proved
      to be a molecule with remarkable antimicrobial properties, even when added in
      closed systems at low concentration.

PMID- 11442816
TI  - Pleomorphism of the marine bacterium Teredinobacter turnirae.
AB  - AIMS: A morphology transition for the marine bacterium, Teredinobacter turnirae
      is reported. METHODS AND RESULTS: When grown in the rod-shaped morphology, the
      cells require high concentrations of NaCl (0.3 mol x l(-1)) and secrete
      extracellular protease and endoglucanase activity. When this bacterium is grown
      in a medium containing casein as a sole carbon and nitrogen source, a major
      change in morphology to a stable aggregated form is obtained. CONCLUSION: In the
      aggregated morphology, much higher protease production rates (170 Units x ml(-1)
      x d-1 for aggregates vs. 15 Units x ml(-1) x d(-1) for rods, for the same initial
      biomass) and negligible endoglucanase titres are obtained. In addition, the
      aggregated morphology does not require sodium chloride for growth. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The phenomenon reported here describes a novel
      relationship between the cell morphology and the biochemical characteristics of
      the bacterium.

PMID- 11442817
TI  - Correlation between medium acidification and pathogenicity in environmental
      halophilic non-cholera vibrios.
AB  - AIMS: The metabolic characterization and pathogenicity of vibrios isolated from
      seafood were studied. METHODS AND RESULTS: Strains of halophilic vibrios, grown
      in the presence of 0.5% glucose, induced high medium acidification and were non
      culturable after 24 h, while moderately acidifying strains were culturable,
      produced cytotoxins, and remained lethal when inoculated intraperitoneally in
      mice. Highly acidifying strains failed to elicit pathogenicity in vivo and in
      vitro. CONCLUSION: The high acidification of the medium and the self-killing
      activity of NCVs might be considered a significant phenotypic marker of virulence
      and/or cytotoxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: We suggest the medium
      acidification test as possible screening method for pathogenic NCVs in food
      microbiology.

PMID- 11442818
TI  - Differentiation of Enterococcus spp. by cell membrane fatty acid methyl ester
      profiling, biotyping and ribotyping.
AB  - AIMS: Gas chromatographic analysis of cell membrane fatty acid methyl esters
      (FAME), biochemical profiling (biotyping) and EcoRI restriction endonuclease
      profiling of DNA containing ribosomal RNA sequences (ribotyping) were compared
      for differentiation of Enterococcus spp. METHODS AND RESULTS: FAME profiling,
      biotype profiling and ribotyping of 41 strains from retail Swiss-type cheeses and
      five strains from culture collections resulted in 17, 25 and 26 groups,
      respectively, with only two pairs of strains having the same FAME group, biotype
      profile and ribogroup. CONCLUSION: Substantial overlap occurred in groupings
      assigned by the three methods. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Differentiation of Enterococcus spp. strains increases if multiple methods are
      used.

PMID- 11442819
TI  - Differentiation of industrial wine yeast strains using microsatellite markers.
AB  - AIMS: To differentiate nine industrial wine strains of Saccharomyces cerevisiae
      using microsatellite (simple sequence repeats, SSR) markers. METHODS AND RESULTS:
      Six of the strains were indigenous yeasts currently used as high-density starter
      monocultures by the Uruguayan wine industry. Unequivocal differentiation of these
      six native strains and three commercial S. cerevisiae wine strains was achieved
      by PCR amplification and polymorphism analysis of loci containing microsatellite
      markers. CONCLUSION: We recommend the use of this reproducible and simple
      molecular method to routinely discriminate wine yeast strains. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Microsatellites are superior to other methods for typing
      yeasts because the results can be exchanged as quantitative data. Knowledge of
      the frequencies of the alleles for different SSR markers will eventually lead to
      an accurate typing method to identify industrial wine yeast strains.

PMID- 11442820
TI  - Optimization of submerged culture conditions for the mycelial growth and exo
      biopolymer production by Cordyceps militaris.
AB  - AIMS: The objective of the present study was to determine the optimal culture
      conditions for exo-biopolymer production by Cordyceps militaris in shake flask
      culture. METHODS AND RESULTS: The optimal temperature and initial pH for both
      mycelial growth and exo-biopolymer production by Cordyceps militaris in shake
      flask culture were found to be 20 degrees C and 6.0, respectively. Sucrose (40 g
      x l(-1)) and corn steep powder (10 g x l(-1)) were the most suitable carbon and
      nitrogen source for both mycelial growth and exo-biopolymer production.
      CONCLUSION: Under optimal culture conditions, the maximum exo-biopolymer
      concentration in a 5-l jar fermenter indicated 10.3 g x l(-1), which was
      approximately three times higher than that in shake flask culture. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This process can have a significant impact on the
      industrial scale when sucrose and corn steep powder were used as carbon and
      nitrogen source.

PMID- 11442821
TI  - Long-term preservation of strains of Burkholderia cepacia, Pseudomonas spp. and
      Stenotrophomonas maltophilia isolated from patients with cystic fibrosis.
AB  - Long-term preservation methods are important in the maintenance of bacteria for
      downstream research applications. Most clinical laboratories have only limited
      resources for archiving isolates and therefore require cost-effective and simple
      methods. An effective and cheap storage method using debrinated blood and
      maintenance at -80 degrees C is described.

PMID- 11442822
TI  - Effect of oral Bacillus coagulans administration on the density of vancomycin
      resistant enterococci in the stool of colonized mice.
AB  - AIMS: A mouse model of vancomycin-resistant enterococcus (VRE) stool colonization
      was used to study the effect of Bacillus coagulans, a biotherapeutic agent, on
      the density of colonization. METHODS AND RESULTS: VRE-colonized mice received
      orally administered B. coagulans (107 cfu) or saline daily for four days. For one
      VRE strain, the density of VRE at one and four days after treatment was 1.4
      log10cfu x g(-1) lower in experimental vs. control mice (P=0.03), and 35% of
      experimental vs. 0% of control mice had no detectable VRE four days after
      treatment (P=0.03). For two additional strains, there was no statistically
      significant reduction of VRE density in the B. coagulans groups. CONCLUSION: B.
      coagulans therapy reduced the density of colonization for one of three VRE
      strains tested. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests a
      potential role for biotherapeutic agents as a means to reduce the density of VRE
      intestinal colonization.

PMID- 11442823
TI  - Ethanol-induced dimorphism and lipid composition changes in Mucor fragilis CCMI
      142.
AB  - AIMS: To study the effect of ethanol on morphology, lipid production and fatty
      acid profile of Mucor fragilis CCMI 142 cultures. METHODS AND RESULTS: Cell
      inhibition in shake flask cultures due to alcohol toxicity grew linearly from
      0.418 mol x 1(-1) to 0.816 mol x 1(-1) ethanol corresponding to a decrease of
      specific growth rate. The growth inhibition constant took the value of 2.27 mol x
      1(-1). The germination of fungal spores into hyphae is inhibited by
      concentrations from 0.418 mol x 1(-1) to 0.816 mol x 1(-1) ethanol. In this
      range, M. fragilis CCMI 142 spores form, exclusively, budding yeast-like cells
      instead of filaments. Below 0.418 mol 1-1 ethanol the formation of yeast-like
      cells was stimulated and there was a spore germination delay. CONCLUSION: The
      lipid content decreased as the concentration of ethanol increased, and was
      associated with an increase of unsaturated/saturated fatty acid ratio.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The major conclusion of the study is the
      production of an enriched unsaturated fatty acids final product with particular
      emphasis to the presence of gamma-linolenic acid (18:3omega6) a biologically
      active compound with a useful impact in nutraceutical science.

PMID- 11442824
TI  - Bacterial DNA ligases.
AB  - DNA ligases join breaks in the phosphodiester backbone of DNA molecules and are
      used in many essential reactions within the cell. All DNA ligases follow the same
      reaction mechanism, but they may use either ATP or NAD+ as a cofactor. All
      Bacteria (eubacteria) contain NAD+-dependent DNA ligases, and the uniqueness of
      these enzymes to Bacteria makes them an attractive target for novel antibiotics.
      In addition to their NAD+-dependent enzymes, some Bacteria contain genes for
      putative ATP-dependent DNA ligases. The requirement for these different isozymes
      in Bacteria is unknown, but may be related to their utilization in different
      aspects of DNA metabolism. The putative ATP-dependent DNA ligases found in
      Bacteria are most closely related to proteins from Archaea and viruses.
      Phylogenetic analysis suggests that all NAD+-dependent DNA ligases are closely
      related, but the ATP-dependent enzymes have been acquired by Bacterial genomes on
      a number of separate occasions.

PMID- 11442825
TI  - Sites of pH regulation of the urea channel of Helicobacter pylori.
AB  - Helicobacter pylori (Hp) and Streptococcus salivarius (Ss) require intrabacterial
      urease for acid resistance and express a urea channel, UreI. The presence of UreI
      was shown to increase urea permeability approximately 300-fold over that of a non
      polar ureI deletion mutant. Expression of SsUreI in Xenopus oocytes increased
      urea uptake pH independently, whereas HpUreI shows an acidic pH dependence, half
      maximal at pH 6.0. Mutagenesis of all histidines, aspartates, glutamates and the
      lysine in the periplasmic domain of HpUreI showed that His-123, His-131, Asp-129,
      Asp-140, Glu-138 and Lys-132 in the second periplasmic loop (PL2) and His-193 in
      the C-terminus (Ct) were important for activation of transport. With the
      exception of a lysine that was shown to substitute for His-193 in HpUreI, these
      charged amino acids are absent in SsUreI. A chimera in which PL1 of HpUreI was
      replaced by PL1 of SsUreI retained activity at acidic pH and gained partial
      activity at neutral pH. Exchange of PL2 inactivated transport, whereas exchange
      of Ct had no effect. Chimeras, in which either PL1 or PL2 of HpUreI replaced
      those of SsUreI, retained wild-type transport, but replacement of the Ct or both
      loops inactivated transport. PL1 appears to be important for restricting
      transport through HpUreI at neutral pH, whereas protonation of three histidines
      in PL2 and Ct and the presence of three dicarboxylic amino acids in PL2 appears
      to be necessary to activate HpUreI at acidic pH.

PMID- 11442826
TI  - The roles of the multiple CheW and CheA homologues in chemotaxis and in
      chemoreceptor localization in Rhodobacter sphaeroides.
AB  - Rhodobacter sphaeroides has multiple homologues of most of the Escherichia coli
      chemotaxis genes, organized in two major operons and other, unlinked, loci. These
      include cheA1 and cheW1 (che Op1) and cheA2, cheW2 and cheW3 (che Op2). We have
      deleted each of these cheA and cheW homologues in-frame and examined the
      chemosensory behaviour of these strains on swarm plates and in tethered cell
      assays. In addition, we have examined the effect of these deletions on the polar
      localization of the chemoreceptor McpG. In E. coli, deletion of either cheA or
      cheW results in a non-chemotactic phenotype, and these strains also show no
      receptor clustering. Here, we demonstrate that CheW2 and CheA2 are required for
      the normal localization of McpG and for normal chemotactic responses under both
      aerobic and photoheterotrophic conditions. Under aerobic conditions, deletion of
      cheW3 has no significant effect on McpG localization and only has an effect on
      chemotaxis to shallow gradients in swarm plates. Under photoheterotrophic
      conditions, however, CheW3 is required for McpG localization and also for
      chemotaxis both on swarm plates and in the tethered cell assay. These phenotypes
      are not a direct result of delocalization of McpG, as this chemoreceptor does not
      mediate chemotaxis to any of the compounds tested and can therefore be considered
      a marker for general methyl-accepting chemotaxis protein (MCP) clustering. Thus,
      there is a correlation between the normal localization of McpG (and presumably
      other chemoreceptors) and chemotaxis. We propose a model in which the multiple
      different MCPs in R. sphaeroides are contained within a polar chemoreceptor
      cluster. Deletion of cheW2 and cheA2 under both aerobic and photoheterotrophic
      conditions, and cheW3 under photoheterotrophic conditions, disrupts the cluster
      and hence reduces chemotaxis to any compound sensed by these MCPs.

PMID- 11442827
TI  - alpha-Enolase of Streptococcus pneumoniae is a plasmin(ogen)-binding protein
      displayed on the bacterial cell surface.
AB  - Binding of human plasminogen to Streptococcus pneumoniae and its subsequent
      activation promotes penetration of bacteria through reconstituted basement
      membranes. In this study, we have characterized a novel pneumococcal surface
      protein with a molecular mass of 47 kDa, designated Eno, which specifically binds
      human plasmin(ogen), exhibits alpha-enolase activity and is necessary for
      viability. Using enzyme assays, we have confirmed the alpha-enolase activity of
      both pneumococcal surface-displayed Eno and purified recombinant Eno protein.
      Immunoelectron microscopy indicated the presence of Eno in the cytoplasm as well
      as on the surface of encapsulated and unencapsulated pneumococci. Plasminogen
      binding activity was demonstrated with whole pneumococcal cells and purified Eno
      protein. Binding of activated plasminogen was also shown for Eno; however, the
      affinity for plasmin is significantly reduced compared with plasminogen. Results
      from competitive inhibition assays indicate that binding is mediated through the
      lysine binding sites in plasmin(ogen). Carboxypeptidase B treatment and amino
      acid substitutions of the C-terminal lysyl residues of Eno indicated that the C
      terminal lysine is pivotal for plasmin(ogen)-binding activity. Eno is
      ubiquitously distributed among pneumococcal serotypes, and binding experiments
      suggested the reassociation of secreted Eno to the bacterial cell surface. The
      reassociation was also confirmed by immunoelectron microscopy. The results
      suggest a mechanism of plasminogen activation for human pathogens that might
      contribute to their virulence potential in invasive infectious processes.

PMID- 11442828
TI  - AraC/XylS family members, HilC and HilD, directly bind and derepress the
      Salmonella typhimurium hilA promoter.
AB  - During infection, Salmonella enterica serovar Typhimurium colonizes the small
      intestine of its hosts. This process requires a type III secretion system encoded
      by several genes on Salmonella pathogenicity island 1 (SPI1), a 40 kb region of
      DNA near centisome 63 of the Salmonella chromosome. SPI1 gene expression is
      controlled by a complex regulatory cascade. HilA, a member of the OmpR/ToxR
      family of transcriptional regulators, directly activates the expression of two
      SPI1 operons encoding type III apparatus components. hilA transcription is
      repressed by many environmental conditions and regulatory mutations. This
      repression requires an upstream repressing sequence (URS) located between -314
      and -68 relative to the hilA transcription start site. The repressing activity of
      the URS is counteracted by two AraC/XylS family members named HilC and HilD. We
      show that HilC and HilD bind directly to the hilA promoter region in vitro. We
      also provide evidence that HilC and HilD bind to the same or overlapping sites
      within the URS. Our data are consistent with a model in which HilC and HilD
      derepress hilA expression by binding directly to the URS and counteracting its
      repressing effect in vivo.

PMID- 11442829
TI  - The recX gene potentiates homologous recombination in Neisseria gonorrhoeae.
AB  - In the pathogen Neisseria gonorrhoeae (Gc), the RecA protein is necessary for DNA
      repair, DNA transformation and pilus antigenic variation. Many bacteria contain a
      gene, recX, which has been suggested to downregulate recA through an unknown
      mechanism. To investigate the possible role of recX in Gc, we cloned and
      insertionally inactivated the recX gene. The recX loss-of-function mutant showed
      decreases in pilus phase variation, DNA transformation and DNA repair ability
      compared with wild type. We were able to complement all these deficiencies by
      supplying a functional copy of recX elsewhere in the chromosome. The recX mutant
      still showed increases in pilus phase variation under conditions of iron
      starvation, and the recX mutant showed levels of RecA protein equivalent to wild
      type. Although the precise role of recX in recombination remains unclear, RecX
      aids all RecA-related processes in Gc, and this is the first demonstration of a
      role for recX in homologous recombination in any organism.

PMID- 11442830
TI  - Carbon catabolite repression in Aspergillus nidulans involves deubiquitination.
AB  - The best studied role of ubiquitination is to mark proteins for destruction by
      the proteasome but, in addition, it has recently been shown to promote
      macromolecular assembly and function, and alter protein function, thus playing a
      regulatory role distinct from protein degradation. Deubiquinating enzymes, the
      ubiquitin-processing proteases (ubps) and the ubiquitin carboxy-terminal
      hydrolases (uchs), remove ubiquitin from ubiquitinated substrates. We show here
      that the creB gene involved in carbon catabolite repression in Aspergillus
      nidulans encodes a functional member of the novel subfamily of the ubp family
      defined by the human homologue UBH1, thus implicating ubiquitination in the
      process of carbon catabolite repression. Members of the novel subfamily of ubps
      that include CreB are widespread amongst eukaryotes, with homologues present in
      mammals, nematodes, Drosophila and Arabidopsis, but mutations in the genes have
      only been identified in A. nidulans. From phenotypes of the A. nidulans mutants
      it is probable that this subfamily is involved in complex regulatory pathways.
      Mutations in the gene encoding the WD40 repeat protein CreC result in an
      identical phenotype, implicating both genes in this pathway.

PMID- 11442831
TI  - degS (hhoB) is an essential Escherichia coli gene whose indispensable function is
      to provide sigma (E) activity.
AB  - DegS (HhoB), a putative serine protease related to DegP/HtrA, regulates the basal
      and induced activity of the essential Escherichia coli sigma factor sigma (E),
      which is involved in the cellular response to extracytoplasmic stress. DegS
      promotes the destabilization of the sigma (E)-specific anti-sigma factor RseA,
      thereby releasing sigma (E) to direct gene expression. We demonstrate that degS
      is an essential E. coli gene and show that the essential function of DegS is to
      provide the cell with sigma (E) activity. We also show that the putative active
      site of DegS is periplasmic and that DegS requires its N-terminal transmembrane
      domain for its sigma (E)-related function.

PMID- 11442832
TI  - The highly conserved domain of the Caulobacter McpA chemoreceptor is required for
      its polar localization.
AB  - We have fused GFP to the C-terminus of McpA to study chemoreceptor polar
      localization in Caulobacter crescentus. The full-length McpA-GFP fusion is
      polarly localized and methylated. The methylation is dependent on the
      chemoreceptor methyltransferase (cheR) and chemoreceptor methylesterase (cheB)
      genes present in the mcpA operon. C-terminal and internal deletions of McpA were
      constructed and fused to the N-terminus of GFP to identify the domains required
      for polar localization. When the R1 methylation domain was deleted, the McpA-GFP
      fusion was still polarly localized, suggesting that this domain is dispensable
      for polar localization. However, when the highly conserved domain (HCD), which is
      involved in interacting with CheW, was deleted either by an internal deletion or
      C-terminal deletion, the resulting McpA-GFP fusions were completely delocalized.
      When the mcpA operon, which contains the cheW and cheA homologues, was deleted,
      the full-length McpA-GFP fusion was delocalized. Although additional chemotaxis
      genes are required for the polar localization of McpA-GFP, the presence of the
      single polar flagellum is not required. However, in filamentous cells, which are
      frequently found in C. crescentus fliF mutants, the McpA-GFP fusion was observed
      at mid-cell positions.

PMID- 11442833
TI  - Roles of trehalose phosphate synthase in yeast glycogen metabolism and
      sporulation.
AB  - Trehalose is a major storage carbohydrate in budding yeast, Saccharomyces
      cerevisiae. Alterations in trehalose synthesis affect carbon source-dependent
      growth, accumulation of glycogen and sporulation. Trehalose is synthesized by
      trehalose phosphate synthase (TPS), which is a complex of at least four proteins.
      In this work, we show that the Tps1p subunit protein catalyses trehalose
      phosphate synthesis in the absence of other TPS components. The tps1-H223Y allele
      (glc6-1) that causes a semidominant decrease in glycogen accumulation exhibits
      greater enzyme activity than wild-type TPS1 because, unlike the wild-type enzyme,
      TPS activity in tps1-H223Y cells is not inhibited by phosphate. Poor sporulation
      in tps1 null diploids is caused by reduced expression of meiotic inducers encoded
      by IME1, IME2 and MCK1. Furthermore, high-copy MCK1 or heterozygous hxk2
      mutations can suppress the tps1 sporulation trait. These results suggest that the
      trehalose-6-phosphate inhibition of hexokinase activity is required for full
      induction of MCK1 in sporulating yeast cells.

PMID- 11442834
TI  - The elimination of the yeast [PSI+] prion by guanidine hydrochloride is the
      result of Hsp104 inactivation.
AB  - In the yeast Saccharomyces cerevisiae, Sup35p (eRF3), a subunit of the
      translation termination complex, can take up a prion-like, self-propagating
      conformation giving rise to the non-Mendelian [PSI+] determinant. The replication
      of [PSI+] prion seeds can be readily blocked by growth in the presence of low
      concentrations of guanidine hydrochloride (GdnHCl), leading to the generation of
      prion-free [psi-] cells. Here, we provide evidence that GdnHCl blocks seed
      replication in vivo by inactivation of the molecular chaperone Hsp104. Although
      growth in the presence of GdnHCl causes a modest increase in HSP104 expression
      (20-90%), this is not sufficient to explain prion curing. Rather, we show that
      GdnHCl inhibits two different Hsp104-dependent cellular processes, namely the
      acquisition of thermotolerance and the refolding of thermally denatured
      luciferase. The inhibitory effects of GdnHCl protein refolding are partially
      suppressed by elevating the endogenous cellular levels of Hsp104 using a
      constitutive promoter. The kinetics of GdnHCl-induced [PSI+] curing could be
      mimicked by co-expression of an ATPase-negative dominant HSP104 mutant in an
      otherwise wild-type [PSI+] strain. We suggest that GdnHCl inactivates the ATPase
      activity of Hsp104, leading to a block in the replication of [PSI+] seeds.

PMID- 11442835
TI  - SeqA, the Escherichia coli origin sequestration protein, is also a specific
      transcription factor.
AB  - The SeqA protein is a negative regulator of initiation of DNA replication in the
      Escherichia coli chromosome. Here, we demonstrate that SeqA stimulates
      transcription from the bacteriophage lambda pR promoter both in vivo and in
      vitro. The activity of the lambda pL promoter was found not to be affected by
      this protein. SeqA-mediated stimulation of pR was dependent on the state of
      template methylation: transcription was activated on fully methylated and
      hemimethylated templates but not on an unmethylated template. Using
      electrophoretic mobility shift assay and electron microscopy, we demonstrated
      that SeqA interacts specifically with a pR promoter region located on both fully
      methylated and hemimethylated DNA molecules, but not on unmethylated DNA. The
      activity of SeqA was found to affect the initiation of lambda plasmid replication
      positively in vivo, probably via pR-dependent expression of lambda replication
      genes and transcriptional activation of ori lambda. We conclude that, apart from
      its function in the control of DNA replication, SeqA is also a specific
      transcription factor.

PMID- 11442836
TI  - Role of the response regulator RssB in sigma recognition and initiation of sigma
      proteolysis in Escherichia coli.
AB  - In growing Escherichia coli cells, the master regulator of the general stress
      response, sigmaS (RpoS), is subject to rapid proteolysis. In response to stresses
      such as sudden carbon starvation, osmotic upshift or shift to acidic pH, sigmaS
      degradation is inhibited, sigmaS accumulates and numerous sigmaS-dependent genes
      with stress-protective functions are activated. sigmaS proteolysis is dependent
      on ClpXP protease and the response regulator RssB, whose phosphorylated form
      binds directly to sigmaS in vitro. Here, we show that substitutions of aspartate
      58 (D58) in RssB, which result in higher sigmaS levels in vivo, produce RssB
      variants unable to bind sigmaS in vitro. Thus, RssB is the direct substrate
      recognition factor in sigmaS proteolysis, whose affinity for sigmaS depends on
      phosphorylation of its D58 residue. RssB does not dimerize or oligomerize upon
      this phosphorylation and sigmaS binding, and RssB and sigmaS exhibit a 1:1
      stoichiometry in the complex. The receiver as well as the output domain of RssB
      are required for sigmaS binding (as shown in vivo and in vitro) and for
      complementation of an rssB null mutation. Thus, the N-terminal receiver domain
      plays an active and positive role in RssB function. Finally, we demonstrate that
      RssB is not co-degraded with sigmaS, i.e. RssB has a catalytic role in the
      initiation of sigmaS turnover. A model is presented that integrates the details
      of RssB-sigmaS interaction, the RssB catalytic cycle and potential stress signal
      input in the control of sigmaS proteolysis.

PMID- 11442837
TI  - The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in
      Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae FPS1 gene encodes a glycerol channel protein
      involved in osmoregulation. We present evidence that Fps1p mediates influx of the
      trivalent metalloids arsenite and antimonite in yeast. Deletion of FPS1 improves
      tolerance to arsenite and potassium antimonyl tartrate. Under high osmolarity
      conditions, when the Fps1p channel is closed, wild-type cells show the same
      degree of As(III) and Sb(III) tolerance as the fps1Delta mutant. Additional
      deletion of FPS1 in mutants defective in arsenite and antimonite detoxification
      partially suppresses their hypersensitivity to metalloid salts. Cells expressing
      a constitutively open form of the Fps1p channel are highly sensitive to both
      arsenite and antimonite. We also show by direct transport assays that arsenite
      uptake is mediated by Fps1p. Yeast cells appear to control the Fps1p-mediated
      pathway of metalloid uptake, as expression of the FPS1 gene is repressed upon
      As(III) and Sb(III) addition. To our knowledge, this is the first report
      describing a eukaryotic uptake mechanism for arsenite and antimonite and its
      involvement in metalloid tolerance.

PMID- 11442838
TI  - Glycosylation with heptose residues mediated by the aah gene product is essential
      for adherence of the AIDA-I adhesin.
AB  - The diffuse adherence of Escherichia coli strain 2787 (O126:H27) is mediated by
      the autotransporter adhesin AIDA-I (adhesin-involved-in-diffuse-adherence)
      encoded by the plasmid-borne aidA gene. AIDA-I exhibits an aberrant mobility in
      denaturing gel electrophoresis. Deletion of the open reading frame (ORF) A
      immediately upstream of aidA restores the predicted mobility of AIDA-I, but the
      adhesin is no longer functional. This indicates that the mature AIDA-I adhesin is
      post-translationally modified and the modification is essential for adherence
      function. Labelling with digoxigenin hydrazide shows AIDA-I to be glycosylated.
      Using carbohydrate composition analysis, AIDA-I contains exclusively heptose
      residues (ratio heptose:AIDA-I approximately 19:1). The deduced amino acid
      sequence of the cytoplasmic open reading frame (ORF) A gene product shows
      homologies to heptosyltransferases. In addition, the modification was completely
      abolished in an ADP-glycero-manno-heptopyranose mutant. Our results provide
      direct evidence for glycosylation of the AIDA-I adhesin by heptoses with the ORF
      A gene product as a specific (mono)heptosyltransferase generating the functional
      mature AIDA-I adhesin. Consequently, the ORF A gene has been denoted 'aah'
      (autotransporter-adhesin-heptosyltransferase). Glycosylation by heptoses
      represents a novel protein modification in eubacteria.

PMID- 11442839
TI  - Disruptions of the Ustilago maydis REC2 gene identify a protein domain important
      in directing recombinational repair of DNA.
AB  - The REC2 gene of Ustilago maydis encodes a homologue of the Escherichia coli RecA
      protein and was first identified in a screen for UV-sensitive mutants. The
      original isolate, rec2-1, was found to be deficient in repair of DNA damage,
      genetic recombination and meiosis. We report here that the rec2-197 allele, which
      was constructed by gene disruption, retains some biological activity and is
      partially dominant with respect to REC2. The basis for the residual activity is
      probably as a result of expression of a diffusible product from the rec2-197
      allele that augments or interferes with REC2 functions. This product appears to
      be a polypeptide expressed from a remnant of the 5' end of the open reading frame
      that was not removed in creating the gene disruption. The mutator activity and
      disturbed meiosis of rec2-197 suggest that the Rec2 protein functions in a
      process that avoids spontaneous mutation and insures faithful meiotic chromosome
      segregation. A prediction based on the phenotype of rec2-197 is that Rec2 protein
      interacts with one or more other proteins in directing these functions. To
      identify interacting proteins we performed a yeast two-hybrid screen and found
      Rad51 as a candidate. Rec2-197 and Rad51 appear to interact to a similar degree.

PMID- 11442840
TI  - Unique regulation of SclB - a novel collagen-like surface protein of
      Streptococcus pyogenes.
AB  - Slipped-strand mispairing at sites containing so-called coding repeats (CRs) can
      lead to phase variation of surface proteins in Gram-negative bacteria. This
      mechanism, believed to contribute to virulence, has so far not been identified in
      a Gram-positive bacterium. In the genome of the Gram-positive human pathogen
      Streptococcus pyogenes, we identified pentanucleotide CRs within a putative
      signal sequence of an open reading frame (ORF) encoding a novel collagen-like
      surface protein, denoted SclB. In 12 S. pyogenes strains, the number of CRs in
      the sclB gene varied from three to 19, rendering the start codon in frame with
      the downstream ORF in four strains and out of frame in eight strains. A protein
      reacting with anti-SclB antibodies could only be solubilized from three strains,
      all containing an intact sclB gene. Variations in the number of CRs were observed
      within strains of the same M serotype and occurred during growth of S. pyogenes
      in fresh human blood, but not in medium. The SclB protein has a hypervariable N
      terminal part, a collagen-like central part and a typical cell wall sorting
      sequence containing the LPXTGX motif. SclB is related to the collagen-like SclA
      and is, like SclA, involved in the adhesion of S. pyogenes bacteria to human
      cells. However, the Mga protein, known to upregulate sclA and several additional
      genes encoding virulence factors of S. pyogenes, downregulates sclB
      transcription. This observation and the potential of SclB to phase vary by
      slipped-strand mispairing emphasize the unique regulation of this novel S.
      pyogenes surface protein.

PMID- 11442841
TI  - Impact of the regulatory loci agr, sarA and sae of Staphylococcus aureus on the
      induction of alpha-toxin during device-related infection resolved by direct
      quantitative transcript analysis.
AB  - The cytotoxic alpha-toxin (encoded by hla) of Staphylococcus aureus is regulated
      by three loci, agr, sarA and sae, in vitro. Here, we assess the regulation of hla
      in a guinea pig model of device-related infection by quantifying RNAIII (the
      effector molecule of agr) and hla directly in exudates accumulating in infected
      devices without subculturing of the bacteria. LightCycler reverse transcription
      polymerase chain reaction (RT-PCR) was used to quantify the transcripts. Strains
      RN6390 and Newman expressed considerably smaller amounts of RNAIII in the guinea
      pig than during in vitro growth. The residual RNAIII expression decreased during
      the course of infection and was negatively correlated with bacterial densities.
      As with RNAIII, the highest hla expression was detected in both strains early in
      infection. Even in strain Newman, a weak hla producer in vitro, a pronounced
      expression of hla was observed during infection. Likewise, four S. aureus
      isolates from cystic fibrosis (CF) patients expressed Q1hla despite an inactive
      agr during device-related infection as in the CF lung. Mutation of agr and sarA
      in strain Newman and RN6390 had no consequence for hla expression in vivo. In
      contrast, the mutation in sae resulted in severe downregulation of hla in vitro
      as well as in vivo. In conclusion, S. aureus seems to be provided with regulatory
      circuits different from those characterized in vitro to ensure alpha-toxin
      synthesis during infections.

PMID- 11442842
TI  - Solute-binding protein-dependent ABC transporters are responsible for solute
      efflux in addition to solute uptake.
AB  - The ATP-binding cassette (ABC) transporter superfamily is one of the most
      widespread of all gene families and currently has in excess of 1100 members in
      organisms ranging from the Archaea to manQ1. The movement of the diverse solutes
      of ABC transporters has been accepted as being strictly unidirectional, with
      recent models indicating that they are irreversible. However, contrary to this
      paradigm, we show that three solute-binding protein-dependent (SBP) ABC
      transporters of amino acids, i.e. the general amino acid permease (Aap) and the
      branched-chain amino acid permease (Bra) of Rhizobium leguminosarum and the
      histidine permease (His) of Salmonella typhimurium, are bidirectional, being
      responsible for efflux in addition to the uptake of solutes. The net solute
      movement measured for an ABC transporter depends on the rates of uptake and
      efflux, which are independent; a plateau is reached when both are saturated. SBP
      ABC transporters promote active uptake because, although the Vmax values for
      uptake and efflux are not significantly different, there is a 103-104 higher
      affinity for uptake of solute compared with efflux. Therefore, the SBP ABC
      transporters are able to support a substantial concentration gradient and provide
      a net uptake of solutes into bacterial cells.

PMID- 11442843
TI  - Immunoglobulin G response of periodontitis patients to Porphyromonas gingivalis
      capsular carbohydrate and lipopolysaccharide antigens.
AB  - Porphyromonas gingivalis clonal types that participate in periodontal infections
      express serologically distinct surface antigens. This investigation sought to
      determine whether serum antibodies titers against the serotype-specific capsular
      carbohydrate K antigen and lipopolysaccharide antigens of P. gingivalis might
      reveal which serotypes are most likely to be responsible for subgingival
      infections in subjects with adult periodontitis. Immunoglobulin G (IgG) titers to
      purified K antigen and lipopolysaccharide from different P. gingivalis strains
      were measured by ELISA for 28 healthy controls and 51 patients with periodontal
      pockets known to be infected with genetically and serologically distinct P.
      gingivalis clonal types. Titers to purified K antigen from strains W50, HG184,
      A7A1-28, 49417, HG1690 and HG1691, representing serotypes K1-K6, respectively,
      and lipopolysaccharide from strains 381, HG1691 and W50, representing serotypes
      O1-O3, respectively, were measured for all subjects. Chi-square likelihood
      ratios, Mann-Whitney tests and receiver-operating characteristic sensitivity
      specificity plots were used to compare the accuracy with which titer results for
      different target antigens classified subjects with or without disease. Results
      from assays targeting K2, K3, K4, K5, O1 and O2 generally gave poor diagnostic
      accuracy, whether evaluated separately or as summed titer pairs corresponding to
      the K/O combinations actually expressed by the target antigen parent strains.
      Exceptions were O3 (from W50) and K5+O2 (both from HG1690), which gave moderate
      accuracy in classifying subjects. In contrast, highly significant diagnostic
      accuracy was achieved using individual K1 (W50) and K6 (HG1691) titer data and
      K1+O3 (W50) and K6+O2 (HG1691) titer sum values. These observations suggest that
      P. gingivalis clonal types expressing K/O serotypes matching those of W50 (K1/O3)
      and HG1691 (K6/O2) are more likely than others to participate in periodontal
      infections in adult periodontitis patients and thus are more likely than others
      to express relevant virulence factors.

PMID- 11442844
TI  - Functional characteristics of antibodies induced by Arg-gingipain (HRgpA) and Lys
      gingipain (Kgp) from Porphyromonas gingivalis.
AB  - Arginine-specific gingipain (HRgpA) and lysine-specific gingipain (Kgp), enzymes
      produced by Porphyromonas gingivalis, may be candidates for an anti-P. gingivalis
      vaccine. The purpose of our study was to determine whether HRgpA and Kgp have
      opsonic target sites and whether these sites are available and accessible on
      intact P. gingivalis cells. Rabbits were used to generate polyclonal antibodies
      to both proteins. Animals were immunized and immunoglobulin G (IgG) fractions
      were isolated from preimmune and immune sera. Functional characteristics of the
      antibodies were assessed by determining antibody titers by enzyme-linked
      immunosorbent assay (ELISA), generating Western immunoblots, and measuring
      antibody enhancement of P. gingivalis opsonization, phagocytosis and killing by
      polymorphonuclear leukocytes (PMN) of intact cells of strains of P. gingivalis
      representative of the four serotypes. Strains studied included 33277 (serotype
      A), A7A1-28 (serotype B), W50 (serotype C) and 381 (serotype D). Both HRgpA and
      Kgp induced high titers of IgG antibody. Anti-HRgpA and anti-Kgp bound to both
      HRgpA and Kgp demonstrating a large proportion of shared antigenic epitopes. The
      two antibodies bound equally well to all four P. gingivalis serotypes with titers
      ranging from 77 to 205 ELISA units when compared to preimmune IgG set at 1 ELISA
      unit. The immunoblot patterns of binding of the two antibodies to HRgpA and Kgp
      and to sonicates of the four P. gingivalis serotypes were virtually identical.
      Both antibodies detected components in HRgpA at 27, 35 and 45 kDa and in Kgp at
      27, 32, 35, 40 and 55 kDa. The antibodies also detected components at or near
      these same positions in addition to multiple high molecular mass components in
      the cell sonicates of P. gingivalis. Both proteins induced antibodies that
      significantly enhanced opsonization as assessed by chemiluminescence, with values
      ranging from 130 mV to 375 mV for anti-HRgpA IgG and from 240 mV to 475 mV for
      anti-Kgp IgG. Both antibodies significantly enhanced PMN-mediated bacterial
      killing of the four P. gingivalis serotypes, although the percentage of killing
      varied among the serotypes (24-81% for anti-HRgpA and 37-89% for anti-Kgp). Thus,
      both HRgpA and Kgp express opsonic target sites and induce high titers of
      antibodies that opsonize and enhance killing of all four serotypes of P.
      gingivalis. These two proteins appear to be potential candidate antigens for an
      anti-P. gingivalis vaccine.

PMID- 11442845
TI  - Studies on the aminopeptidase activities of Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is an asaccharolytic bacterium that requires nitrogen
      substrates as carbon and energy sources. The aims of this study were to
      investigate the aminopeptidase activities of P. gingivalis and to evaluate the
      effect of aminopeptidase inhibitors on bacterial growth. Only arginine
      aminopeptidase and dipeptidyl aminopeptidase IV activities were detected.
      Experimental evidence was obtained suggesting that the Arg-gingipains of P.
      gingivalis can function as both an endopeptidase and an aminopeptidase. Firstly,
      the arginine aminopeptidase activity was found to be inhibited by leupeptin, a
      well-known inhibitor of Arg-gingipain activity. Secondly, a preparation of Arg
      gingipain activity could hydrolyze the chromogenic substrate for arginine
      aminopeptidase. Lastly, a mutant of P. gingivalis constructed via gene disruption
      by use of suicide plasmids and deficient in both Arg-gingipain A and B was also
      devoid of arginine aminopeptidase activity. To investigate the key role of
      aminopeptidase activities in growth of P. gingivalis, aminopeptidase inhibitors
      were incorporated in the culture medium prior to inoculation. Bestatin and
      actinonin were the only ones to inhibit growth of P. gingivalis. Their mechanism
      of growth inhibition appears to be different but does not involve inhibition of
      the two major aminopeptidase activities (arginine aminopeptidase and dipeptidyl
      aminopeptidase IV).

PMID- 11442846
TI  - The recA gene in Porphyromonas gingivalis is expressed during infection of the
      murine host.
AB  - The recA gene in Porphyromonas gingivalis is involved in DNA repair. To further
      elucidate the importance of the recA locus in the pathogenesis of P. gingivalis,
      we assessed its ability for expression in an animal host. The promoterless xa
      tetA(Q)2 cassette was used in heterodiploid mutants to study recA promoter
      activity during infection. P. gingivalis FLL118.1 had the xa-tetA(Q)2 cassette
      under the control of recA promoter whereas P. gingivalis FLL119 had the cassette
      in the opposite orientation. xa encodes a bifunctional xylosidase/arabinosidase
      enzyme (XA) and the tetA(Q)2 gene product confers tetracycline resistance.
      Intramuscular infection in a mouse model allowed the recovery of the bacteria
      from inguinal lymph nodes. Infusion of tetracycline in the animals permitted the
      enrichment P. gingivalis FLL118.1 over the wild-type strain, during a mixed
      infection. The xylosidase activity of FLL118.1 could be detected on agar plates
      in the presence of 5-methylumbellifiry-beta-D-xyloside. No such enrichment for
      xylosidase activity was detected when the mixture of P. gingivalis W83 and P.
      gingivalis FLL119 was used to infect the mouse or cultured in vitro. These
      results indicated that recA promoter was transcriptionally active during the
      infection of the murine host and further support the importance of this locus
      during the P. gingivalis infection process.

PMID- 11442847
TI  - Distribution of the tetracycline resistance determinant tetQ gene in oral
      isolates of black-pigmented anaerobes in Japan.
AB  - We investigated the distribution of tetracycline resistance determinant tetQ in
      oral black-pigmented anaerobes using a polymerase chain reaction (PCR) METHOD: A
      total of 185 healthy subjects were divided into 3 groups based on subject age:
      young (6 to 10 years, n=58), middle (11 to 40 years, n=96), and elder (exactly 70
      years, n=31). The prevalence of black-pigmented anaerobes in the gingival sulcus
      among these groups was 29.3%, 28.2%, and 64.5%, respectively. The prevalence of
      Prevotella nigrescens among these groups was 22.4%, 15.6%, and 32.3%,
      respectively, whereas the prevalence of Prevotella intermedia was 1.7%, 4.2%, and
      35.5%, respectively. Porphyromonas gingivalis was found only in the elder group
      (16.1%). The prevalence of the tetQ gene in the black-pigmented anaerobes
      positive subjects was almost the same among the 3 groups (approximately 30%). The
      tetQ gene was found in 27.5% (46 of 167) of P. nigrescens isolates, whereas it
      was found in only 6.4% (3 of 47) of P. intermedia isolates and in none of the 19
      P. gingivalis isolates. Restriction endonuclease digestion patterns of the PCR
      products revealed 83.6% of 49 tetQ-positive isolates were of subtype A2H2 (AluI
      type 2, HpaII type 2).

PMID- 11442848
TI  - Porphyromonas endodontalis binds, reduces and grows on human hemoglobin.
AB  - Porphyromonas endodontalis is a black-pigmented, obligate anaerobic rod-shaped
      bacterium implicated as playing a major role in endodontic infections. We have
      previously shown that P. endodontalis requires the porphyrin nucleus, preferably
      supplied as hemoglobin, as a growth supplement. The bacteria also actively
      transport free iron, although this activity does not support growth in the
      absence of a porphyrin source. The purpose of this study was to further
      investigate the binding and subsequent utilization of human hemoglobin by P.
      endodontalis. P. endodontalis binds hemoglobin and reduces the Fe(III) porphyrin,
      resulting in a steady accumulation of ferrous hemoglobin. Reduction of
      methemoglobin was similar to the extracellular reduction of nitrobluetetrazolium
      in the presence of oxidizable substrate. Turbidimetric and viable cell
      determinations showed that P. endodontalis grew when supplied only hemoglobin.
      Therefore, we conclude that hemoglobin appears to serve as a sole carbon and
      nitrogen source, and that these bacteria reduce extracellular compounds at the
      expense of oxidized substrates.

PMID- 11442849
TI  - Phenotypic and genotypic diversity of Streptococcus sanguis in infants.
AB  - Streptococcus sanguis comprises a heterogeneous group of oral streptococci
      indigenous to the oral cavity of humans. A total of 289 isolates from an infant
      population (n=37) were tentatively identified as S. sanguis on the basis of the
      distinctive colony morphology as shown on MM10-sucrose non-selective medium.
      These isolates were divided into four biovars of S. sanguis as determined by an
      extended panel of biochemical attributes. Chromosomal DNA was extracted from each
      isolate, and an AP-PCR fingerprint profile was obtained to allow study of the
      diversity within and among the infants. In this study, all four biovars of S.
      sanguis were detected in the infants. A wide genotypic diversity of S. sanguis
      was observed among these isolates; on average, each infant harbored 2.7 unique
      amplitypes as shown by the AP-PCR fingerprints. To explore the phylogenic
      relationship among these S. sanguis isolates, 20 strains representing the four
      biovars were selected at random for sequencing of their 16S rDNA and 16S-23S rDNA
      intergenic spacer chromosomal loci. Two major sequence patterns were identified
      within the 16S rDNA sequences. A phylogenic analysis showed that members from
      each of the four biovars of S. sanguis bore close relationship with the type
      strain ATCC 10556 sequence, and that all of the isolates representing the four
      biovars could be clustered into two main phylotypes. The biovars were distributed
      throughout the phylotypes, indicating no correlation between the genetic and
      phenotypic groupings.

PMID- 11442850
TI  - Increase of Candida cell virulence by anticancer drugs and irradiation.
AB  - The influence of anticancer drugs and irradiation on Candida cell proliferation,
      adherence to HeLa cells and susceptibility to antifungal drugs (amphotericin B
      and miconazole) and neutrophils were examined using two Candida albicans strains.
      After treatment with 5-fluorouracil (25 microg/ml to 250 microg/ml), cis-diammine
      dichloroplatinum (10 microg/ml to 100 microg/ml), peplomycin (0.5 microg/ml to 5
      microg/ml) or 137Cs (20 Gy to 40 Gy) for 3 days or more, surviving Candida cells
      proliferated more rapidly than did untreated control cells. Anticancer agent
      pretreated Candida cells revealed an increased adhesion to HeLa cells
      corresponding to an increase of binding to the lectins. The concentration of half
      limited colony formation (IC50) of amphotericin B and miconazole was increased to
      near two-fold that of the control by pretreatment of Candida cells with the
      anticancer agents, except peplomycin, which only weakly increased IC50. In
      addition, the enolase and Candida acid proteinase activities in the culture
      supernatants were increased by pretreatment with the drugs and irradiation.
      Correspondingly, surviving Candida cells after these treatments were resistant to
      neutrophils, with a reduction to half of the killing. These results indicate that
      anti-cancer drugs and irradiation potentiate the virulence of Candida cells, or
      they eliminate Candida cells with low virulence, thereby enhancing the risk of
      oral and systemic candidiasis.

PMID- 11442851
TI  - Antifungal activity of histatin-5 against non-albicans Candida species.
AB  - Fungicidal effects of histatin-5 against 26 oral isolates belonging to 5 non
      albicans Candida species were examined. Fifty microM of histatin-5 killed more
      than 95% of Candida tropicalis and Candida guilliermondii isolates and more than
      90% of Candida parapsilosis and Candida krusei. However, Candida glabrata was
      less sensitive to the peptide (mean 62.9%). Our results, taken together,
      demonstrated that histatin-5 possessed the fungicidal activity against Candida
      species other than C. glabrata.

PMID- 11442852
TI  - Antimicrobial effect of acidified nitrite on periodontal bacteria.
AB  - The antimicrobial agent nitric oxide (NO) is formed in the mouth and its
      concentration is directly related to salivary nitrite, which in turn is related
      to dietary nitrate intake. The aim of this study was to determine whether nitrite
      under acidic conditions will have an inhibitory effect, possibly occurring
      through NO production, on the periodontal disease pathogens Fusobacterium
      nucleatum, Eikenella corrodens and Porphyromonas gingivalis. Whereas the growth
      of these organisms was inhibited by a more acid pH, the addition of nitrite
      caused a marked, further dose-dependent reduction in bacterial numbers after
      exposure. The ability of these bacteria to recover from nitrite exposure was also
      affected by pH and nitrite concentration. At acidity levels below pH 5.0, low
      concentrations of nitrite (0.2 mM) caused effective complete killing of the
      periodontal bacteria. Addition of sodium thiocyanate did not increase the
      bacteriostatic or bacteriocidal activity of acidified nitrite against any of the
      3 bacteria. These results demonstrate the possibility that nitrite in saliva,
      under appropriate conditions, may have an effect on the growth and survival of
      the bacteria implicated in periodontal disease.

PMID- 11442853
TI  - What we don't know about childhood obstructive sleep apnoea.

PMID- 11442854
TI  - Anaesthesia and laparoscopic surgery in children.

PMID- 11442855
TI  - An audit of perioperative management of autistic children.
AB  - BACKGROUND: Autistic children are very difficult to manage in the hospital
      setting because they react badly to any change in routine. METHODS: We have
      developed a unique management program for autistic children admitted for medical
      and surgical procedures requiring a general anaesthetic. Details of each patient
      managed according to this program have been prospectively entered into an
      Autistic Register. RESULTS: An audit of this database shows that we have
      administered anaesthesia on 87 occasions for 59 autistic children over 4 years.
      CONCLUSIONS: There is great variation in the severity of autism and hospital
      needs of these children. The focus is on early communication with the patient's
      families, flexibility to individualize the admission process and anaesthetic plan
      with admission and early discharge on the day of surgery whenever possible. Oral
      midazolam is an effective premedication for the milder cases and oral ketamine is
      the most reliable for moderate and severe cases. Comparison of oral midazolam and
      ketamine shows no significant different postoperative recovery and hospital
      discharge times. Routine intravenous fluids and antiemesis prophylaxis with
      removal of the i.v. cannula before return to the ward are also seen as important
      steps to decrease stress and smooth the postoperative phase. This program has
      also successfully been extended to the management of problem children due to
      other causes.

PMID- 11442856
TI  - Prediction of difficult airway in school-aged patients with microtia.
AB  - BACKGROUND: Because the ear and mandible develop from the first and second
      branchial arches and first branchial cleft, abnormalities of the ear may be a
      sign that intubation will be difficult. We hypothesized that children with
      microtia would have a greater incidence of difficult laryngeal visualization with
      conventional rigid laryngoscopy compared to those with normal facial anatomy.
      METHODS: We enrolled 93 consecutive school-aged patients with microtia undergoing
      the first stage of total reconstruction of the auricle. Age-matched patients with
      normal facial anatomy served as controls. Each patient was examined for the
      presence or absence of the five dysmorphic features of hemifacial microsomia:
      orbital asymmetry, mandibular hypoplasia, ear deformity, nerve involvement, soft
      tissue deficiency (OMENS classification). After a standardized induction of
      anaesthesia, the laryngeal view during rigid laryngoscopy was graded. RESULTS:
      The incidence of difficult laryngeal view was 42% in the patients with bilateral
      microtia, 2% in those with unilateral microtia and 0% in the controls.
      CONCLUSIONS: There was a strong positive correlation between the number of
      involved abnormal anatomical components according to the OMENS classification and
      the degree of difficult visualization of the larynx in patients with both
      bilateral and unilateral microtia (Spearman rank order correlation
      coefficient=0.85 and 0.88, respectively).

PMID- 11442857
TI  - Pharmacokinetics and analgesic effect of ropivacaine following
      ilioinguinal/iliohypogastric nerve block in children.
AB  - BACKGROUND: The aim was to investigate the efficacy, tolerance and
      pharmacokinetics of ropivavcaine when administered for
      ilioinguinal/iliohypogastric block in children. METHODS: We examined the
      pharmacokinetics and analgesic efficacy after ilioinguinal/iliohypogastric nerve
      block with 3 mg.kg-1 ropivacaine 5 mg.ml-1 in 22 children, aged 1-12 years, who
      were scheduled for inguinal surgery. Sixteen of 22 patients had a postoperative
      pain score < 4 (Objective Pain Scale). Nine children were given supplementary
      analgesics during the first six postoperative hours. RESULTS: The peak plasma
      concentration of total ropivacaine was 1.50 +/- 0.93 mg.l-1 (mean +/- SD) (range
      0.64-4.77 mg.l-1) 15-64 min after the injection. The peak plasma concentration of
      free ropivacaine was 0.05 +/- 0.03 mg.l-1 (0.02-0.14 mg.l-1), which is well below
      the threshold for toxicity in adults. The terminal half-life was 2.0 +/- 0.7 h.
      No safety concerns or symptoms suggestive of systemic toxicity were observed.
      CONCLUSION: A dose of 3 mg.kg-1 of ropivacaine given as a single
      ilioinguinal/iliohypogastric nerve block in 1-12-year-old children provides
      satisfactory postoperative pain relief, and is well tolerated.

PMID- 11442858
TI  - The effect on intraocular pressure of tracheal intubation or laryngeal mask
      insertion during sevoflurane anaesthesia in children without the use of muscle
      relaxants.
AB  - BACKGROUND: We studied the effects of sevoflurane on intraocular pressure after
      induction in children undergoing either tracheal tube (TT) or laryngeal mask
      airway (LMA) insertion without a muscle relaxant METHODS: The study included 38
      children. Anaesthesia was induced (8%) and maintained (3-4%) with sevoflurane in
      100% O2. No muscle relaxant was used. A TT was inserted in group I (n=20), and an
      LMA in group II (n=18). IOPs were measured after induction, insertion of TT or
      LMA and at 1, 2 and 3 min thereafter. The heart rate, mean arterial pressures
      were also recorded. RESULTS: Intraocular pressures increased significantly in
      group I after TT (P < 0.01) and remained high until after 3 min. The pressures
      were similar in the LMA group at all measurements. CONCLUSION: Sevoflurane does
      not prevent the increase in IOP after intubation without muscle relaxants. LMA
      does not increase IOP in children after sevoflurane induction.

PMID- 11442859
TI  - Distal oesophageal pH measurement in children during general anaesthesia using
      the laryngeal mask airway, tracheal tube and face mask.
AB  - BACKGROUND: Distal oesophageal pH was measured during controlled ventilation in
      children with the laryngeal mask airway (LMATM), tracheal tube (TT) and face mask
      (FM). METHODS: Fifty-six children scheduled for inguinal surgery with a
      standardized general anaesthetic technique were randomly allocated to receive LMA
      (n=21), TT (n=18) or FM (n=19). A 14 Fr pH probe was placed into the distal
      oesophagus and pH values were measured over 1 min at 2-min intervals during the
      first 20 min of anaesthesia. RESULTS: The median values of pH were 4.4 (3.5-5.5),
      4.2 (3.3-4.9), 4.1 (3.2-5.1), 4.1 (3.3-5.0), 4.0 (3.3-4.9), 4.0 (3.4-5.1); 4.2
      (3.3-5.1), 4.2 (3.6-5.0), 4.2 (3.5-5.0), 4.2 (3.5-5.2), 4.2 (3.5-5.0), 4.1 (3.5
      5.0) and 4.2 (3.6-5.0), 4.2 (3.8-5.8), 4.1 (2.8-5.2), 4.2 (3.3-5.1), 4.2 (3.4
      5.1), 4.3 (3.4-5.1) for LMA, TT and FM groups, respectively. CONCLUSION: There
      was no difference in the median pH values, within and between the groups (P >
      0.05). We conclude that there is no difference in gastro-oesophageal reflux, when
      using a LMA, TT or FM during controlled ventilation in anaesthetized children.

PMID- 11442860
TI  - Unlicensed and off label analgesic use in paediatric pain management.
AB  - BACKGROUND: The management of pain in children has advanced enormously in recent
      years. Pharmacological treatment of pain is complicated however, by the
      widespread use of unlicensed and off label medicines in the paediatric
      population, leading to everyday practical problems. This study aimed to document
      the incidence and nature of unlicensed and off label analgesic agents in
      children. METHODS: Data regarding analgesic use were collected prospectively over
      a 4-week period from two wards. The data were analysed to determine whether the
      drug use was licensed, unlicensed or off label. RESULTS: Seven hundred and
      fifteen prescription episodes were analysed. Some 480 of these (67%) were
      licensed; 235 were licensed medicines used in an off label manner (33%). No
      medicines were unlicensed. Paracetamol was the most common analgesic used.
      CONCLUSION: Issues regarding the use of off label drugs in children at risk of
      pain are discussed. Suggestions are made regarding the way forward for the
      future.

PMID- 11442861
TI  - Survey of the use of oesophageal and precordial stethoscopes in current
      paediatric anaesthetic practice.
AB  - BACKGROUND: The aim of the study was to examine the use of oesophageal and
      precordial stethoscopes for monitoring in current paediatric anaesthetic practice
      in the UK and Ireland. METHODS: A postal survey of members of the Association of
      Paediatric Anaesthetist of Great Britain and Ireland was undertaken. RESULTS: One
      hundred and forty-five questionnaires were returned with a response rate of
      67.4%. Some 35.2% of anaesthetists never use an oesophageal or precordial
      stethoscope and the majority of the remaining 64.8% use one in less than one
      third of their practice. CONCLUSION: Use of the stethoscope as a continuous
      monitor has decreased and most anaesthetists feel it has been superseded by other
      monitoring. However, almost one-third of anaesthetists recorded critical
      incidents they had been involved with where an oesophageal or precordial
      stethoscope detected the incident early. Complications of these monitoring
      devices were rare and the main factors limiting their use was the presence of
      better monitoring, such as pulse oximetry and capnography, and lack of
      availability.

PMID- 11442862
TI  - Comparison of recovery after intermediate duration of anaesthesia with
      sevoflurane and isoflurane.
AB  - BACKGROUND: The purpose of this study was to compare recovery from anaesthesia
      after sevoflurane and isoflurane were administered to children for more than 90
      min. METHODS: After parental informed consent and ethical committee approval,
      children aged between 2 months and 6 years, ASA I or II, were randomly allocated
      to sevoflurane (n=20) or isoflurane (n=20) groups. Halogenated agents were
      discontinued following skin closure and patients were ventilated mechanically
      with 100% oxygen until minimum alveolar concentration (MAC) values awake were
      obtained (endtidal concentrations 0.6 MAC for sevoflurane and 0.4 MAC for
      isoflurane). Effective perioperative analgesia was provided by a caudal block.
      RESULTS: The mean (+/- SD) duration of anaesthesia was 132 +/- 38 min and 139 +/-
      49 min for sevoflurane and isoflurane, respectively. Early recovery occurred
      sooner in the isoflurane group (time to extubation was 16 +/- 7 min and 11 +/- 5
      min, P<0.01; Aldrete's score at 0 min was 5.5 +/- 1.5 and 7.4 +/- 1.8, P<0.001,
      respectively). But the time to be fit for discharge from recovery room was
      similar at 136 +/- 18 min and 140 +/- 20 min, respectively. CONCLUSIONS: After
      intermediate duration of anaesthesia administered to children for up to 90 min,
      isoflurane and sevoflurane allow recovery after approximatively the same lapse of
      time.

PMID- 11442863
TI  - Assessment of pain by parents in young children following surgery.
AB  - BACKGROUND: We asked parents to assess pain in young children following surgery.
      METHODS: Assessments were carried out by both parents and an independent assessor
      using a behavioural observational scale. RESULTS: Forms were returned from the
      parents of 42 children aged 1-5 years. There were 123 joint assessments and there
      was a strong correlation between the scores by the observer and the parents
      (r2=0.84). Twenty-nine children experienced pain following discharge from
      hospital. CONCLUSION: Our findings suggest that parents can assess pain in young
      children following surgery. The management of pain following discharge from
      hospital can be improved.

PMID- 11442864
TI  - Pain management in children with and without cognitive impairment following spine
      fusion surgery.
AB  - BACKGROUND: We compared pain assessment and management practices in children with
      and without cognitive impairment (CI) undergoing spine fusion surgery. METHODS:
      The medical records of 42 children (19 with CI and 23 without) were reviewed and
      data related to demographics, surgery, pain assessment and management, and side
      effects were recorded. RESULTS: Fewer children with CI were assessed for pain on
      postoperative days (POD) 0-4 compared to those without CI (P < 0.002). Self
      report was used for 81% of pain assessments in children without CI, while a
      behavioural tool was used for 75% of assessments in cognitively impaired
      children. Children with CI received smaller total opioid doses on POD 1-3
      compared to those without CI (P < or = 0.02). Furthermore, children without CI
      received patient/nurse-controlled analgesia for more postoperative days than
      children with CI (P=0.02). CONCLUSION: Our data demonstrate a discrepancy in pain
      management practices in children with and without CI following spine fusion.

PMID- 11442865
TI  - Comparison of caudal morphine and tramadol for postoperative pain control in
      children undergoing inguinal herniorrhaphy.
AB  - OBJECTIVES: We compared the quality and duration of analgesia, the effect on
      perioperative sevoflurane requirement after a single, presurgical caudal block
      with either tramadol or morphine in children undergoing inguinal herniorrhaphy.
      Our study was also designed to evaluate the preemptive analgesic efficacy of
      morphine administered caudally in children. METHODS: Patients were randomly
      divided into three groups to receive 2 mg.kg-1 tramadol (group T, preemptive
      group) or morphine sulphate 0.03 mg.kg-1 (group M, preemptive group). The
      patients in control group (group C, postincisional group) received morphine
      sulphate 0.03 mg.kg-1 at the end of surgery, caudally. Cardiorespiratory data,
      sedation and pain were recorded for 24 h following recovery from anaesthesia.
      RESULTS: There were no differences between the three groups in baseline blood
      pressure or heart rate; or duration of anaesthesia, surgery. The inhaled
      sevoflurane concentration was significantly lower in group M and group T than in
      the control group. The quality and duration of postoperative pain relief did not
      differ between the three groups. There were no intergroup differences in
      postoperative nausea, vomiting, or other complications. CONCLUSION: Caudal
      tramadol (2 mg.kg-1) provided reliable postoperative analgesia similar to caudal
      morphine (0.03 mg.kg-1) in quality and duration of pain relief in our study
      children who were undergoing herniorrhaphy. We also concluded that presurgical
      caudal morphine or tramadol reduced perioperative sevoflurane requirements and
      either presurgical or postsurgical caudal morphine did not make any difference to
      postoperative analgesia.

PMID- 11442866
TI  - Early tracheal extubation after paediatric cardiac surgery: the use of propofol
      to supplement low-dose opioid anaesthesia.
AB  - BACKGROUND: After institutional approval and parental consent, 103 children, aged
      6 months to 18 years, who were undergoing repair of simple and complex congenital
      heart lesions using cardiopulmonary bypass (CPB) were studied and compared with a
      group of 135 children who had undergone similar surgery in our institution in the
      year before. METHODS: Anaesthesia for study patients included fentanyl (< 20
      microg.kg-1) and isoflurane. Infusions of propofol (median infusion rate 70
      microg.kg-1.min-1) and morphine (median infusion rate 20 microg.kg-1.h-1) were
      started after weaning from CPB and continued postoperatively. Preestablished
      criteria were used in the intensive care unit (ICU) to assess readiness for
      tracheal extubation. RESULTS: Median time from admission to ICU to tracheal
      extubation was 5 h. Fifty-six children were extubated within 6 h and 73 within 9
      h of ICU admission. Mean ICU stay for study patients was 1.7 days [95% confidence
      interval (CI) 1.2-2.2] and 2.6 days (95% CI 2.3-2.9) in the comparison group
      (P<0.005). CONCLUSIONS: We found the propofol regimen to be satisfactory with a
      shorted ICU stay for these patients.

PMID- 11442867
TI  - Review of ethics in paediatric anaesthesia: research issues.
AB  - This is the second of a series of three articles reviewing the recent changes in
      the law in relation to ethics and the practice of paediatric anaesthesia. The
      review covers, in a practical question and answer format, the topics of consent,
      research, intensive care issues and organ donation in children.

PMID- 11442868
TI  - Mediastinal mass obscured by a large pericardial effusion in a child: a potential
      cause of serious anaesthetic morbidity.
AB  - Anaesthesia in the presence of a mediastinal mass is known to be hazardous. We
      report a case of a 5-year-old boy with a presumed postviral pericardial effusion
      presenting for pericardiocentesis under general anaesthesia. Cardiorespiratory
      collapse following induction of anaesthesia occurred due to an undiagnosed
      mediastinal tumour. The reasons for misdiagnosis, mechanisms for perioperative
      complications and optimal management are discussed. Mediastinal masses and
      underlying malignancy should always be considered in patients with large
      pericardial effusions.

PMID- 11442869
TI  - Anaesthetic management and high frequency oscillatory ventilation.
AB  - In an effort to decrease morbidity and mortality, newer modes of mechanical
      ventilation have been introduced into the critical care arena. One such
      technique, high frequency oscillatory ventilation (HFOV) relies on respiratory
      rates greater than 150 b.min-1, small tidal volumes, and the maintenance of a
      constant distending pressure thereby limiting peak inflating pressure and
      potentially the incidence of barotrauma. Despite the frequent application of this
      technique in the ICU setting, there is limited information concerning its
      intraoperative use. We present three infants who represent the perioperative
      applications of HFOV: (i) elective preoperative use to minimize lung movement and
      interference with surgical exposure during thoracotomy and PDA ligation; (ii)
      intraoperative application when progressive alterations in respiratory compliance
      led to ineffective intraoperative ventilation/oxygenation; and (iii) anaesthetic
      care for a neonate already receiving HFOV. The techniques of HFOV and previous
      reports of perioperative use are reviewed.

PMID- 11442870
TI  - Anaesthetic considerations for a child with combined Prader-Willi syndrome and
      mitochondrial myopathy.
AB  - We report the anaesthetic management of a child with Prader-Willi syndrome and
      mitochondrial myopathy for open heart surgery. We used ketamine, fentanyl,
      rocuronium and caudal morphine together with a propofol infusion with no untoward
      effects. The implications of both conditions for anaesthesia are discussed.

PMID- 11442871
TI  - Cervical subcutaneous emphysema: an unusual complication of adenotonsillectomy.
AB  - Removal of the tonsils and adenoid tissue because of recurrent infection and/or
      respiratory obstruction is one of the most commonly performed operations. A rare
      complication during this intervention is subcutaneous surgical emphysema. The
      awareness of anaesthesiologists and otolaryngological surgeons will protect the
      patient from serious consequences. We report our experience with this
      complication and provide a review of the literature.

PMID- 11442872
TI  - Anaesthetic management of a patient with myotonic dystrophy.
AB  - A 13-year-old boy with myotonic dystrophy underwent insertion of a percutaneous
      gastrostomy feeding tube under general anaesthesia. We used a laryngeal mask
      airway and a spontaneously breathing technique with propofol total intravenous
      anaesthesia. Postoperative vomiting and aspiration, 12 h after the procedure,
      subsequently required intubation and ventilation. We discuss the anaesthetic
      management of this case and review the features of the disease to be considered
      when contemplating anaesthesia in such patients.

PMID- 11442873
TI  - Anaesthetic management of a child with a positive family history of malignant
      hyperthermia for posterior fossa surgery in the sitting position.
AB  - A 6-year-old boy with a positive family history of malignant hyperthermia
      presented for posterior fossa craniectomy and excision of medulloblastoma. A
      nontriggering anaesthetic was therefore planned using infusions of propofol and
      remifentanil and a vapour free anaesthetic system delivering an oxygen/air
      mixture. The surgery was carried out with the child in the sitting position.

PMID- 11442874
TI  - Complicated airway management in a child with prune-belly syndrome.
AB  - We describe a 15-month-old boy with prune-belly syndrome (PBS) in whom airway
      management was complicated. Following an inhalation induction using sevoflurane,
      tracheal intubation by direct laryngoscopy proved impossible after repeated
      attempts. A laryngeal mask airway (LMAtrade mark) was inserted and the child had
      an uneventful anaesthetic course.

PMID- 11442875
TI  - Doppler ultrasound guided vascular access needle in paediatric patients.

PMID- 11442877
TI  - Intraosseous needles: an essential emergency adjunct in paediatric anaesthesia.

PMID- 11442878
TI  - Successful treatment of intraoperative erection in a 15-month-old child with
      intracavernous epinephrine.

PMID- 11442879
TI  - High spinal anaesthesia in a formerly preterm infant undergoing pyloromyotomy.

PMID- 11442880
TI  - Alterations of nitric oxide and monoamines in the brain of the EL mouse treated
      with phenobarbital and zonisamide.
AB  - The effects of phenobarbital (PB; doses, 5, 10, and 25 mg/kg, intraperitoneally
      (i.p.)) and zonisamide (ZNS; doses, 30, 75, and 150 mg/kg, i.p.) on nitric oxide
      (NO) production, and those of coadministration of PB (5 mg/kg, i.p.) and ZNS (75
      mg/kg, i.p.) on monoamines in the brain of the seizure-susceptible EL mouse were
      investigated. Nitric oxide production was obtained by measuring the combined
      level of nitrite plus nitrate (NOx). Zonisamide and PB dose-dependently
      suppressed the seizure of the EL mouse, and coadministration of PB (5 mg/kg) and
      ZNS (75 mg/kg) induced a greater degree of seizure suppression than treatment
      with ZNS or PB alone. Although PB (5 mg/kg) had no effect on brain NOx levels,
      ZNS (150 mg/kg) and coadministration of ZNS (75 mg/kg) and PB (5 mg/kg) decreased
      NOx levels significantly. Phenobarbital (5 mg/kg) did not influence monoamines,
      while coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) decreased
      dihydroxyphenylacetic acid and increased 5-HT concentrations. The effect of the
      coadministration of two drugs on monoamines were similar to that of ZNS alone.
      These results suggest that one of the anticonvulsant effects of coadministration
      of PB and ZNS may be caused by changes in NOx levels.

PMID- 11442881
TI  - Influences of caffeine to nitric oxide production and zonisamide concentration in
      the brain of seizure-susceptible EL mice.
AB  - To investigate changes of nitric oxide (NO) productions and zonisamide (ZNS)
      concentrations in the brain of seizure-susceptible EL mice given caffeine orally,
      mice were given caffeine (600 microg/mL) solution ad libitum as a drinking fluid
      for 1-3 weeks. Nitric oxide production in the brain was determined by measuring
      levels of nitrite plus nitrate (NOx). The brain NOx levels of mice treated with
      caffeine for 3 weeks were significantly higher than the control. Seizures in mice
      treated with caffeine for 2 and 3 weeks were not suppressed by ZNS at a dose of
      75 mg/kg. Serum ZNS concentrations of mice with caffeine intake for 1-3 weeks
      were higher than in untreated mice. Conversely, brain ZNS concentrations of mice
      with caffeine intake for the same periods were significantly lower than in
      untreated mice. These results suggested that caffeine influenced brain NO
      production and ZNS concentrations in the seizure susceptibility of EL mice.

PMID- 11442882
TI  - Hypothalamically induced emotional behavior and immunological changes in the cat.
AB  - Numerous animal studies on the correlation between stress and immunity have been
      performed but few such studies have been made concerning the relationship between
      various kinds of stress-related emotional behavior and immunological changes.
      Electrical stimulation of the hypothalamus in cats elicits various emotional
      behaviors such as restlessness, defensive attack, defensive retreat and quiet
      biting attack. We examined changes in the lymphocyte proliferative responses and
      plasma cortisol level which accompanied such emotional behavior. A significant
      increase in plasma cortisol was observed in the restlessness, defensive attack
      and defensive retreat groups, but not in the quiet biting attack or non-response
      (control) groups. A significant increase in the lymphocyte proliferative
      responses to phytohemagglutinin (PHA) was observed in the restlessness and
      defensive attack groups but not in the defensive retreat, quiet biting attack or
      non-response groups. These results suggest that various kinds of emotional
      behavior appear to be differentially correlated with the lymphocyte proliferative
      responses, while also being differentially correlated with the plasma cortisol
      concentration. Because the changes in lymphocyte responses and plasma cortisol
      did not always completely correlate with one another, the changes in the
      lymphocyte responses are not considered to be influenced by plasma cortisol
      alone.

PMID- 11442883
TI  - Physical and sexual abuse histories in patients with eating disorders: a
      comparison of Japanese and American patients.
AB  - Physical and sexual abuse among patients with eating disorders has been a focus
      of attention in Western countries, however, there is no study comparing the
      incidence of these factors in Western and Asian countries. Japanese subjects
      consisted of 38 patients with anorexia nervosa restricting type (AN-R), 46
      patients with anorexia nervosa binge eating/purging type (AN-BP), 76 patients
      with bulimia nervosa purging type (BN) and 99 controls. Subjects from the USA
      consisted of 29 AN-R, 34 AN-BP and 16 BN. The Physical and Sexual Abuse
      Questionnaire was administered to all subjects. Minor sexual abuse such as
      confronting exhibitionism or being fondled by a stranger tended to be more
      prevalent among Japanese subjects, while victimization by rape or incest was more
      prevalent among USA subjects. Conversely, physical abuse history was similarly
      distributed across each diagnostic subgroup in both countries. Events related to
      physical abuse, such as an abusive family background, may contribute whether
      eating disorder patients are restricting or bulimic and regardless of culture.

PMID- 11442884
TI  - Effects of combination psychotropic drug treatment on heart rate variability in
      psychiatric patients.
AB  - The aim of this study was to evaluate the effects of combination psychotropic
      drug treatment on heart rate variability (HRV), which was mainly controlled by
      the parasympathetic nervous system. Mean R-R intervals (mRR) and coefficient of
      variation (CV), an index of HRV, were studied in 22 psychiatric patients and 21
      age- and sex-matched healthy controls. Next, in the patient group focusing on
      both anticholinergic and antidopaminergic properties, combination psychotropic
      drug daily doses were converted into biperiden milligram equivalents (BPDeq) and
      chlorpromazine milligram equivalents (CPZeq), respectively. The relationship
      between mRR and CV and these equivalent dosages was examined. A significant
      reduction in both mRR (P < 0.05) and CV (P < 0.05) was found in the patient
      group. In addition, significant negative correlations were observed between the
      dose of BPDeq and mRR (P < 0.05), and between the dose of BPDeq and CV (P <
      0.005). In contrast, no significant correlations were observed between the dose
      of CPZeq and either parameter. These findings suggest that the effects of
      combination psychotropic drug treatment on HRV are mainly due to their
      anticholinergic properties. Therefore, CV is a useful indicator to assess the
      parasympathetic activity of psychiatric patients under combination psychotropic
      drug treatment.

PMID- 11442885
TI  - Changes in auditory P300 with clinical remission in schizophrenia: effects of
      facial-affect stimuli.
AB  - The auditory P300 is affected by arousal and emotion. We examined the effect of
      drawings expressing sadness or pleasure on auditory event-related potentials
      (ERP) during recovery from schizophrenia. Oddball-paradigm auditory ERP were
      recorded while presenting one of these drawings to nine patients with paranoid
      schizophrenia and seven patients with other types of schizophrenia during the
      acute stage and again during remission. P300 parameters (amplitude, area, and
      latency), reaction time, and symptom scores were evaluated. P300 amplitude and
      area were significantly greater in the recovery than in the acute phase.
      Increases were larger when viewing drawings that expressed sadness than when
      viewing drawings that expressed pleasure. In paranoid-type patients, P300 when
      viewing pleasurable drawings was similar to that when viewing sad drawings during
      the acute phase; in remission, P300 was significantly larger when viewing sad
      drawings than when viewing pleasurable drawings. In non-paranoid patients, P300
      while viewing pleasurable drawings was significantly larger than that while
      viewing sad drawings during the acute phase; this difference disappeared during
      recovery. P300 latency and reaction time were not influenced by facial-affect
      stimuli or recovery. A significant negative correlation was noted between
      amplitude and negative symptom scores. P300 amplitude and area may be useful
      state markers during recovery in schizophrenic patients. Effects involving
      attention resources and emotional arousal are also involved.

PMID- 11442886
TI  - Efficacy and safety of olanzapine, an atypical antipsychotic, in patients with
      schizophrenia: results of an open-label multicenter study in Japan.
AB  - This first clinical study of olanzapine in Japanese patients with schizophrenia
      was conducted to investigate the efficacy and safety of olanzapine. Eighty-one
      patients were included in the analysis set. Mean modal dose for those patients
      were 9.4 +/- 3.6 mg/day. For the primary efficacy measure (Final Global
      Improvement Rating score), 14.8% of patients had remarkable improvement, 59.3% of
      patients had moderate improvement or better, and 86.4% of patients had slight
      improvement or better. Results from the Brief Psychiatric Rating Scale showed
      improvement from baseline in all clusters including positive psychotic symptoms
      (thought disturbance) but also against negative symptoms (anergia). The most
      commonly reported treatment-emergent signs and symptoms with > or =10% incidence,
      were insomnia, weight increase, excitement, sleepiness, and anxiety. There was a
      low incidence of extrapyramidal treatment-emergent signs and symptoms, and events
      reported were tremor (6.2%), muscle rigidity (3.7%), and akathisia (2.5%). The
      most commonly reported treatment-emergent laboratory changes, with > or = 20% of
      incidence, were prolactin elevations (24.3%) followed by increases in
      triglycerides (20.4%). However, mean prolactin values tended to be normalized
      during the study. This study result suggests that olanzapine is an "atypical"
      antipsychotic.

PMID- 11442887
TI  - Visual event-related potential in mild dementia of the Alzheimer's type.
AB  - Visual event-related potentials (ERP) and behavioral measures were recorded
      during a geometrical-figure discrimination task to examine sensory processing in
      10 patients with mild dementia of the Alzheimer's type (DAT) and 10 age-matched
      controls. No difference existed between the groups in P1, N1, and P2 potentials,
      which reflects the early stage of sensory processing, as well as in NA potential,
      which reflects pattern recognition. The patients showed reduced amplitude of P3
      potential, retarded reaction time, and increased behavioral errors compared to
      controls. These findings suggest that the patients with mild DAT were intact in
      early sensory processing including pattern recognition but were selectively
      compromised in higher-level processing, including integration of information and
      memory matching, which may influence behavioral deviation.

PMID- 11442888
TI  - CYP2D6*4 polymorphism is not associated with Parkinson's disease and has no
      protective role against Alzheimer's disease in the Korean population.
AB  - CYP2D6*4 polymorphism is reported to be associated with Parkinson's disease (PD)
      and to have protective role against Alzheimer's disease (AD). Such findings are
      not extensively studied in the Oriental population, especially Koreans. The
      effects of CYP2D6*4 polymorphism on AD and PD were investigated by polymerase
      chain reaction-restriction fragment length polymorphism in Korean subjects.
      Heterozygous mutant allele was found in four of 93 patients with PD, 0 of 32
      patients with AD and one of 121 control subjects (59 stroke, 59 normal controls
      and four other psychiatric disorders), but no homozygous mutant allele was found.
      There were no statistically significant differences between the AD group and
      controls, and between the PD group and controls. In conclusion, we suggest that
      CYP2D6*4 polymorphism does not confer susceptibility to PD in the Korean
      population. Also, due to such a rare occurrence of the CYP2D6*4 polymorphism, we
      can not confirm the protective role of the polymorphism against AD in the Korean
      population.

PMID- 11442889
TI  - Caregiver depression predicts early discontinuation of care for disabled elderly
      at home.
AB  - This longitudinal study investigates the caregiving experiences among Japanese
      caregivers who provided informal care at home for disabled elderly between 1998
      and 1999. Forty-seven caregivers of the impaired elderly continued caregiving at
      home in Matsuyama Town, a rural area of northern Japan, while 18 caregivers
      discontinued it. The mean score of the Center for Epidemiologic Studies
      Depression Scale in 1998 among those who gave up caregiving was significantly
      higher than that of those who continued caregiving, indicating that depression
      predicts early discontinuation of care in the home. This is one of the few
      studies in Japan to suggest that initial caregiver depression is a factor in the
      decision to terminate care for the disabled elderly at home.

PMID- 11442890
TI  - Correlation of panic attacks and hostility in chronic schizophrenia.
AB  - The aim of this study was to investigate the relationship between panic attacks
      and hostility in patients with chronic schizophrenia. Thirty-two patients with a
      minimum 2-year history of treatment for schizophrenia were interviewed. The
      patients took mood stablizers lithium, carbamazepine and valproate adjunctively
      for hostility and anger attacks. Panic attacks were defined by Structure Clinical
      Interview of DSM-IV. Severity of psychopathology was assessed by the Hamilton
      Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale (BPRS).
      Functional level was assessed by the Global Assessment of Functioning Scale
      (GAF). Eight (25%) patients met the diagnostic criteria for panic attacks (DSM
      IV) with affective symptoms including hostility and sudden spells of anger. Their
      HDRS scores were significantly higher (P < 0.01), and GAF scores were
      significantly lower (P < 0.05) than those of patients without panic attacks.
      Patients with panic attacks displayed significantly higher hostility in the score
      of the BPRS (P = 0.01). Those who received higher doses of neuroleptics were more
      likely to be considered hostile. Multivariate analysis revealed that panic
      attacks were correlated with more severe depression, greater hostility and lower
      GAF scores. The results suggest that increased hostility and anger spells may be
      symptoms of panic attacks, which are overlooked by psychiatrists.

PMID- 11442891
TI  - Outcome of severe anorexia nervosa patients receiving inpatient treatment in
      Japan: an 8-year follow-up study.
AB  - Sixty-one subjects with anorexia nervosa (AN) were followed for a minimum of 4
      years after discharge (mean 8.3 years). They were evaluated using the Morgan
      Russell Outcome Assessment Scale. Thirty-one (51%) were categorized as having
      good outcome, eight (13%) as intermediate, 15 (25%) as poor, and seven (11%) had
      died. As predictors of outcome, later onset (after 20 years of age) and low
      minimum body mass index were associated with poor prognosis. The outcome of AN in
      Japan is relatively similar to those in Western countries, irrespective of
      different sociocultural backgrounds and health systems.

PMID- 11442892
TI  - A survey on the drug therapy for delirium.
AB  - Delirium, which is experienced by 10-30% of inpatients, is commonly seen in daily
      practice. A survey was conducted of the delirium medications, and results were
      obtained from 28 psychiatric departments and related facilities. Haloperidol was
      used in 67% cases for the treatment of delirium. Ninety-seven per cent of
      facilities considered haloperidol as the drug of first choice, while 57% thought
      this drug had few side-effects and was easy to use. However, because the use of
      this drug is not covered by health insurance in Japan, its use is limited. We
      expect that this study on medication for the treatment of delirium will be a
      first step in increasing the approved indications for drugs used for the
      treatment of delirium, and to reduce off-label use.

PMID- 11442893
TI  - Olanzapine versus haloperidol in the treatment of patients with chronic
      schizophrenia: results of the Japan multicenter, double-blind olanzapine trial.
AB  - This randomized double-blind trial was conducted to test the efficacy and safety
      of olanzapine in Japanese patients with schizophrenia. Importantly, this study
      also represents the first large clinical trial of olanzapine conducted in an
      Asian population. Patients (n = 182) were randomly assigned to treatment with
      olanzapine or haloperidol over a period of 8 weeks. The primary analyses
      included: (i) a test of non-inferiority of olanzapine compared with haloperidol
      in efficacy using the Final Global Improvement Rating (FGIR); and (ii) comparison
      between the treatment groups in extrapyramidal symptom severity using the Drug
      Induced Extrapyramidal Symptoms Scale (DIEPSS). Olanzapine was comparable to
      haloperidol in efficacy in treating positive symptoms and significantly superior
      in treating negative symptoms. Extrapyramidal symptom severity was significantly
      improved for olanzapine-treated patients versus haloperidol-treated patients.
      Olanzapine was shown to be more effective and better tolerated than haloperidol
      in the treatment of Japanese patients suffering from chronic schizophrenia.

PMID- 11442894
TI  - Pitch perception shift: a rare side-effect of carbamazepine.
AB  - Carbamazepine-induced pitch perception shifts have rarely been described. Two
      cases of shifted pitch perception developing during medication with carbamazepine
      are described. Case 1 possessed absolute pitch. Her pitch perception shift
      disappeared with the discontinuance of carbamazepine. Case 2 did not have
      absolute pitch. Even though he experienced a pitch perception shift, he developed
      a tolerance to the shift. We concluded that carbamazepine was the cause of the
      pitch perception shift in the first case, while the second case probably became
      attuned to the change in pitch perception because he did not possess absolute
      pitch.

PMID- 11442895
TI  - The manual zero potential shifting method in dipole analysis: comparison with
      neuroimagings in a patient with epilepsy.
AB  - We previously introduced the manual zero potential shifting (MZPS) method into
      dipole analysis to reduce the influence by error potential at the analytical
      stage. The source localizations of epileptic spikes as an equivalent current
      dipole (ECD) were estimated in a patient with symptomatic epilepsy and contrasted
      with findings obtained by magnetic resonance imaging (MRI) and single photon
      emission computed tomography (SPECT). When spikes were analyzed by the MZPS
      method, ECDs had high values of dipolarity, an indicator of ECD reliability.
      Moreover, their locations corresponded with lesions shown by MRI and SPECT. When
      the same spikes were analyzed by the conventional method, dipolarity values were
      declined and the locations did not correspond with lesions. These results provide
      further evidence that the MZPS method is of clinical utility in evaluating the
      electric source generator of epileptic spikes.

PMID- 11442896
TI  - Severe, isolated thrombocytopenia under polytherapy with carbamazepine and
      valproate.
AB  - It is not known whether polytherapy with carbamazepine (CBZ) and valproate (VPA)
      increases the risk of thrombocytopenia. A 67-year-old woman with symptomatic
      epilepsy since age 6 years, classified as Lennox-Gasteau syndrome, developed
      severe, isolated thrombocytopenia of 5 GIGA/L (normal: 150-360 GIGA/L) after
      being on CBZ (1200 mg/day) for 15 days and additional VPA (300 mg/day) for 5 days
      in combination. After discontinuation of CBZ and VPA and two thrombocyte
      transfusions, the thrombocyte count normalized within 3 days. Because she had
      been taking VPA for only 5 days in addition to CBZ, it could not be confirmed
      whether it was CBZ alone or the combination of CBZ and VPA that was responsible
      for the severe thrombocytopenia.

PMID- 11442897
TI  - Association analysis of the 5-HT6 receptor polymorphism C267T with depression in
      patients with Alzheimer's disease.
AB  - A significant increase of 267C allele of the 5-HT(6) receptor gene has been
      reported in patients with Alzheimer's disease (AD). Because a deficit in
      serotonergic neurotransmission is involved in major depression, we tried to find
      out whether 267C allele is associated with depressive disorders in AD. A
      psychiatrist interviewed all AD patients and their caregivers for evidence of
      depression using a Chinese version of the Standard Clinical Interview for DSM-III
      R. The difference in the 5-HT(6) genotype or allele distributions between the AD
      patients with depressive disorders (n = 25) and those without (n = 120) was not
      significant.

PMID- 11442898
TI  - Usefulness of Biplanar Transesophageal Echocardiography in Arrhythmogenic Right
      Ventricular Dysplasia: Clinical Experience with Seven Cases.
AB  - This study evaluated the clinical usefulness of biplanar transesophageal
      echocardiography (TEE) in suspected arrhythmogenic right ventricular dysplasia
      (ARVD). Seven symptomatic subjects (3 male and 4 female: ages 18-64 years, mean
      45) with clinical features of ARVD (typical ventricular arrhythmias) underwent
      comprehensive noninvasive assessment including transthoracic echocardiography
      (TTE), nuclear magnetic resonance (NMR), and TEE. Other systemic and cardiac
      diseases were reasonably excluded. TEE identified a significant right ventricular
      regional alteration in one subject with negative TTE and NMR, and nonsignificant
      abnormalities in two subjects with negative or no TTE and positive NMR. TEE
      confirmed the pathological findings detected by TTE in the four remaining
      patients and visualized several more abnormalities that approximately
      corresponded to NMR results. On the basis of these initial results, biplanar TEE
      appears to be comparable to NMR in the assessment of ARVD and a promising
      technique in identifying ARVD morphological alterations. (ECHOCARDIOGRAPHY,
      Volume 13, January 1996)

PMID- 11442899
TI  - Quantitative Texture Analysis in Two-Dimensional Echocardiography: Application to
      the Diagnosis of Myocardial Hemochromatosis.
AB  - BACKGROUND: Myocardial reflectivity is abnormally increased in patients with
      thalassemia major under transfusion treatment, probably due to myocardial iron
      deposits and/or secondary structural changes. Such increased reflectivity has
      been detected by both qualitative and subjective analysis of two-dimensional
      echocardiographic (2-D echo) images and quantitative assessment of integrated
      backscatter amplitude with noncommercially available ultrasound prototypes. The
      purpose of this study was to assess the acoustic properties of myocardium in
      patients with beta-thalassemia major and iron overload by means of quantitative
      computerized offline textural analysis of conventionally recorded 2-D echo
      images, and to compare textural data with other qualitative (visual assessment)
      and quantitative (ultrasound backscatter analysis) approaches for myocardial
      ultrasound tissue characterization simultaneously applied to these patients.
      METHODS AND RESULTS: Thirty-five young patients with thalassemia major, without
      clinical signs of cardiac failure, and 20 age and sex matched normal controls
      were studied by echocardiography. Each patient was receiving blood transfusion
      every 2-3 weeks. Two-dimensional echo images, obtained with a commercially
      available echocardiograph using the parasternal long-axis view, were digitized
      off line and analyzed by first and second order texture algorithms applied to
      regions of interest in the myocardium (septal and posterior wall). The mean gray
      level value was higher in thalassemic patients than in controls on both the
      septum (110 +/- 25 vs 57 +/- 13, arbitrary units on a 0-255 scale; P < 0.01) and
      posterior wall (91 +/- 25 vs 67 +/- 18; P < 0.01). Among second order statistical
      parameters, contrast and angular second moment significantly (P < 0.01)
      differentiated septal and posterior walls of patients and controls. In
      thalassemic patients, no consistent correlation was found between wall texture
      parameters and hematologic (years of transfusions and chelation, number of
      transfusions), 2-D echo (posterior wall thickness, left ventricular end-diastolic
      diameter), and Doppler (transmitral E/A waves ratio) parameters. Myocardial walls
      with visually assessed increased echo reflectivity showed a trend toward higher
      values of mean gray level when compared with myocardial segments with
      qualitatively assessed normal reflectivity (septum: 121 +/- 26 vs 106 +/- 24;
      posterior wall: 105 +/- 23 vs 87 +/- 23). Although radiofrequency integrated
      backscatter has been demonstrated to be capable of identifying thalassemic
      patients, no significant correlation was found between mean gray level (by
      texture analysis) and radiofrequency data (septum: r = 0.03; posterior wall: r =
      0.09; P = NS for both). CONCLUSIONS: Myocardial walls affected by hemochromatosis
      show ultrasound image texture alterations that may be quantified with digital
      image analysis techniques and appear mostly unrelated to hematologic and
      conventional, as well as radiofrequency-based, echocardiographic parameters.
      These changes in quantitatively evaluated echo reflectivity are present even
      before the development of clinical and echocardiographic signs of cardiac
      dysfunction. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442900
TI  - Transesophageal Echocardiographic Assessment of Lesions of the Right Ventricular
      Outflow Tract and Pulmonic Valve.
AB  - To establish the role of biplane transesophageal echocardiography (TEE) in the
      assessment of congenital and acquired lesions involving the right ventricular
      outflow tract (RVOT) and pulmonic valve (PV), 28 consecutive RVOT and PV lesions
      in 22 consecutive patients were studied by two-dimensional and color Doppler
      transthoracic echocardiograms (n = 22), horizontal (n = 22) and vertical (n = 22)
      plane TEEs, cardiac catheterization (n = 15), cardiac surgery (n = 6), and
      magnetic resonance imaging (n = 1). Sixteen patients had congenital lesions, and
      six had acquired lesions. Longitudinal TEE clearly imaged 25 of 28 abnormalities,
      transverse TEE clearly imaged 12 of 28, and transthoracic echocardiography
      clearly imaged 9 of 28. Two-dimensional TEE scanning revealed the lesion or site
      of stenosis. Color Doppler revealed conspicuous mosaic jets in relation to a
      structural abnormality in most cases. Longitudinal TEE was more sensitive in the
      detection of small vegetations of the PV, in the depiction of PV doming in cases
      of valvar pulmonic stenosis, and in the display of the RVOT and PV so that the
      longitudinal extent of involvement of larger masses could be appreciated.
      However, longitudinal TEE was not able to assess the gradient of a stenosis at
      the RVOT or PV level in any case. Biplane TEE is helpful in the anatomic
      assessment of congenital and acquired lesions of the RVOT and PV in adults.
      (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442901
TI  - Multivariate Analysis of Left Ventricular Mass Determinants in Adults: Different
      Patterns in Men and Women.
AB  - Echocardiographic left ventricular mass (LVM) estimates are strong predictors of
      subsequent mortality and cardiovascular events. It is known that blood pressure
      (BP), weight (WT), and age are significantly correlated with LVM. We hypothesized
      that stroke volume (SV) measured by Doppler echocardiography would also be
      correlated with LVM. Two hundred and thirteen patients referred for routine
      echocardiography had determination of LVM, cuff BP, and Doppler SV. Those with
      localized LV disease, valvular disease, or cor pulmonale were excluded. In both
      men and women, systolic BP (SBP) was more closely correlated with LVM than was
      diastolic blood pressure or mean arterial pressure, and SV was more closely
      correlated with LVM than cardiac output or cardiac index. Stepwise regression,
      followed by multiple regression showed that four variables (WT, SV, SBP, and AGE)
      explained 32.3% of the variability in LVM in men and 48.5% of the variability in
      LVM in women. WT and SV were significant determinants of LVM in both men and
      women. Age was also significant in men and SBP was also significant in women. For
      both men and women, SV was more significantly correlated with LVM than was SBP.
      The changes in LVM associated with 1 SD increments of SV and SBP, respectively,
      were 8 and 5 g for men and 13 and 11 g for women. We conclude that men and women
      have different patterns of variables influencing LVM. Doppler echocardiographic
      SV is a newly described determinant of LVM that has a greater correlation with
      LVM than does SBP. This study reemphasizes the importance of WT as the major
      determinant of LVM. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442902
TI  - Temporality in Ultrasound-Induced Cell Lysis In Vitro.
AB  - To test the hypothesis that the full extent of in vitro cell lysis due to
      ultrasound becomes evident with time lapse following insonation, human
      erythrocytes (2% hematocrit) in autologous plasma were mixed with Albunex(R), a
      pulse echo contrast agent, and exposed to 1-MHz, continuous-wave ultrasound (US)
      (5 W/cm(2) SPTA intensity) for 60 seconds while in a rotating (200 rpm) dialysis
      membrane vessel. Exposed and sham-exposed samples were subsequently assayed for
      hemolysis colorimetrically, either immediately or after a delay of 3 hours.
      Hemolysis was dependent on the interval between US exposure and assay, with
      significantly greater lysis evident with delayed assay. There was also
      temporality in lytic yield with sample number, i.e., with time postpreparation of
      the blood sample, US-induced cell lysis decreased. The temporality of lytic yield
      was eliminated by maintenance at ice water temperatures, or by waiting about 1
      hour before beginning treatments. The collective data indicate that the full
      extent of US-induced cell lysis is not evident upon assay immediately after
      insonation, and that with time postpreparation and preinsonation, erythrocytes
      may undergo changes in sensitivity to US. (ECHOCARDIOGRAPHY, Volume 13, January
      1996)

PMID- 11442903
TI  - Intraventricular Flow During Isovolumic Relaxation: Comparison of Normal and
      Paced Ectopic Excitation Under Varied Loading Conditions.
AB  - In this study, isovolumetric relaxation time (IVRT) flow velocities recorded by
      pulsed Doppler were induced or augmented in nine patients (aged 60 +/- 20 years)
      with permanent pacemakers. Six subjects had evidence of IVRT flow (>/=0.2 m/sec)
      during native rhythm, only three of whom exhibited cavity obliteration. Mean +/-
      SD left ventricular (LV) ejection fraction and end-diastolic and end-systolic
      volumes were 60% +/- 5%, 104 +/- 50 mL, and 39 +/- 27 mL, respectively. IVRT
      flows were induced or augmented (P < 0.003) in all patients during paced ectopic
      stimulation of the right ventricle and during pacing combined with sublingual
      nitroglycerin (NTG; 0.4 mg). However, IVRT flows were not significantly increased
      with NTG alone. IVRT flow duration was prolonged >50% by pacing (P < 0.05). These
      data suggest that IVRT flows may be present in patients without cavity
      obliteration and may be accentuated by asynchronous LV relaxation.
      (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442904
TI  - Echocardiographic Features of Large Posterobasal Left Ventricular Aneurysms.
AB  - We describe the echocardiographic characteristics of 12 patients with left
      ventricular aneurysms involving posterobasal segments of the ventricular septum
      and of the adjacent ventricular wall. In 5, the septal as well as ventricular
      wall components of the aneurysm were both conspicuous; in 3 the septal but not
      ventricular wall component was large; and in 4 the ventricular wall part of the
      aneurysm was predominant. In all, the mouth (rim) of the aneurysm was wider than
      its fundus, thus distinguishing the posterobasal ventricular aneurysm from a
      pseudoaneurysm. The echographic features are striking, but are easily overlooked
      in standard echo planes. Aneurysmal complications (acquired ventricular septal
      defect, mural thrombus) can also be detected. Together with echo appearances,
      other consistent findings of this entity include deep, wide inferior Q waves,
      posteromedial papillary muscle calcification, and total or subtotal occlusion of
      right coronary or circumflex coronary artery. (ECHOCARDIOGRAPHY, Volume 13,
      January 1996)

PMID- 11442905
TI  - Detection of Abdominal Aortic Aneurysm During Routine Echocardiography.
AB  - OBJECTIVE: To determine the feasibility of detecting abdominal aortic aneurysms
      (AAAs) in the elderly by adding abdominal screening to a standard
      echocardiographic study. METHODS: Prospective consecutive screening was performed
      on 250 patients (men over 55 years and women over 65 years) referred for standard
      echocardiography. After completion of the standard echocardiographic exam,
      abdominal aortic diameter was measured using the echocardiographic transducer.
      RESULTS: Adequate aortic images were obtained in 216 patients. Thirteen aneurysms
      (ranging from 3.3-6.6 cm in diameter, nearly equally divided between men and
      women) were found. CONCLUSIONS: Screening of the abdomen in elderly men and women
      presenting for echocardiographic examination results in a significant yield of
      AAAs. This simple procedure should be added to the standard echocardiographic
      examination in the older population. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442906
TI  - False Aneurysm of the Aortic Root and Right Ventricular Outflow Obstruction: An
      Unusual Complication of Surgically Treated Infective Endocarditis.
AB  - Aortic root abscess often complicates the course of aortic valve endocarditis. In
      severe cases, left ventricular-aortic discontinuity may occur, providing
      challenging technical problems for the surgeon. Moreover, surgical intervention
      sometimes takes place in a semi-emergency context, and the patches and prosthesis
      are sutured into friable tissues and subjected to high systemic pressures.
      Subsequently, paravalvular leaks and prosthesis dehiscence are not uncommon;
      postoperative false aneurysm of the aortic root is a much more unusual
      complication. We report one case of right ventricular outflow obstruction that
      occurred after surgical treatment of an aortic root abscess. Echocardiographic
      data were useful, but magnetic resonance imaging provided valuable information
      about the anatomic extent of the cavity. (ECHOCARDIOGRAPHY, Volume 13, January
      1996)

PMID- 11442907
TI  - Aortic Dissection in Progress Diagnosed by Transthoracic Echocardiography.
AB  - This report describes a patient who presented with vague chest pain, syncope, and
      seizures. The diagnosis of dissection of the ascending aorta was clearly
      established by transthoracic echocardiography. The dissection was initially
      limited to the ascending aorta. Using the suprasternal window, it was possible to
      monitor the progression of the dissection almost beat by beat as it extended from
      the ascending aorta and across the aortic arch to the descending thoracic aorta.
      Surgical intervention was carried out immediately with successful results.
      Although transesophageal echocardiography is the procedure of choice in aortic
      dissection, definitive information can be obtained quickly and safely using the
      transthoracic approach. The suprasternal window in this case showed the dramatic
      progression of the disease process. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442908
TI  - Double Orifice Mitral and Tricuspid Valves.
AB  - Atrioventricular valve duplication is a rare congenital cardiac anomaly. The
      anomaly is usually recognized as an incidental finding at autopsy, open heart
      surgery, or two-dimensional echocardiography. In this article we present the
      transthoracic and transesophageal presentation of a case of mitral and a case of
      tricuspid valve duplication. The hemodynamic consideration of the lesions is
      discussed with a review of the literature. (ECHOCARDIOGRAPHY, Volume 13, January
      1996)

PMID- 11442909
TI  - Atrial Septal Aneurysm and Dilated Sinus of Valsalva in a Patient with Wolff
      Parkinson-White Syndrome.
AB  - Atrial septal aneurysm and a dilated sinus of Valsalva were noted on
      echocardiography in a 30-year-old male with Wolff-Parkinson-White syndrome. The
      relative low probability of all three coexisting by chance alone suggests the
      possibility of a common developmental origin. (ECHOCARDIOGRAPHY, Volume 13,
      January 1996)

PMID- 11442910
TI  - The Role of Multiplane Transesophageal Echocardiography in Diagnosing PDA in an
      Adult.
AB  - The usefulness of multiplane transesophageal echocardiography in diagnosing PDA
      in asymptomatic adults is described. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442911
TI  - Tricuspid Valve Aneurysm Formation in a Child with Suspected Endocarditis.
AB  - Aneurysms of the aortic and mitral valve are a known complication of infective
      endocarditis in adults. We report an unusual case of tricuspid valve endocarditis
      in a child with resultant aneurysm formation as its presenting finding after a
      brief clinical course. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

PMID- 11442912
TI  - Transesophageal Echocardiographic Findings in Sclerosing Mediastinitis.
AB  - We report the usefulness of transesophageal echocardiography in evaluating a
      patient with sclerosing mediastinitis. The technique enabled us to identify a
      mass obstructing the superior vena cava and right upper and lower pulmonary
      veins, and infiltrating and invaginating into the left atrial cavity.
      Transesophageal echocardiography was superior to computed tomography and
      transthoracic echocardiography in delineating these findings. (ECHOCARDIOGRAPHY,
      Volume 13, January 1996)

PMID- 11442913
TI  - Automatic Border Detection to Assess Right Ventricular Function Following
      Surgical Treatment of Thromboembolic Pulmonary Hypertension.
AB  - Automatic border detection (ABD) has been developed as a potentially useful means
      for evaluating ventricular function on line in an automatic fashion. Its success
      with tracking left ventricular function is established, but little is known about
      its ability to assess right ventricular (RV) function. Accordingly, 20 patients
      with severe pulmonary hypertension due to chronic thromboembolic disease
      underwent standard two-dimensional echocardiography and imaging with ABD before
      and after pulmonary thromboendarterectomy to correct pulmonary hypertension. ABD
      derived results were compared to manually planimetered RV areas calculated from
      the apical four-chamber view. Doppler tricuspid regurgitant velocity fell
      significantly with surgery from 4.4 +/- 0.6 to 2.9 +/- 0.7 m/sec (P < 0.001). The
      mean values for RV areas derived by manual planimetry and ABD were similar, as
      was fractional area shortening, which improved significantly with surgery (manual
      0.24 +/- 0.01 preoperative vs 0.31 +/- 0.11 postoperative, P < 0.05; and ABD 0.19
      +/- 0.05 preoperative vs 0.32 +/- 0.15 postoperative, P < 0.001). There was,
      however, very little correlation between the individual values for ABD versus
      manually derived RV areas and fractional area shortening, with the best
      correlation being the RV end-diastolic areas after surgery (y = 0.684x + 7.9, r =
      0.564, P = 0.01). These results demonstrate that both manually planimetered RV
      areas and those determined by ABD can adequately follow changes in ventricular
      function over time. However, variability within each technique may prevent direct
      comparison of the absolute values of the two techniques. (ECHOCARDIOGRAPHY,
      Volume 13, March 1996)

PMID- 11442914
TI  - Influence of Echocardiographic Guidance on Positioning of the Buttoned Occluder
      for Transcatheter Closure of Atrial Septal Defects.
AB  - Ideal position of the buttoned device for occlusion of atrial septal defects was
      achieved more often with transesophageal than with transthoracic
      echocardiographic guidance (10/11 vs 7/23; P = 0.001). Patients with ideal device
      position were less likely to have residual shunts, device unbuttoning, or
      atrioventricular valve regurgitation (2/17 vs 11/17; P = 0.002). We therefore
      recommend the use of transesophageal echocardiography to guide implantation of
      the buttoned device. (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442915
TI  - Atrial Mechanical Function Before and After Electrical or Amiodarone
      Cardioversion in Atrial Fibrillation: Assessment by Transesophageal
      Echocardiography and Pulsed Doppler.
AB  - In some patients with atrial fibrillation (AF), it has been suggested that left
      atrial mechanical dysfunction can develop after successful electrical
      cardioversion, justifying postcardioversion anticoagulant treatment. The purpose
      of this study was to investigate differences in left atrial appendage peak flow
      velocities and the incidence of left atrial spontaneous echo contrast in patients
      with AF before and after electrical cardioversion or intravenous amiodarone,
      studied using transesophageal echocardiography (TEE) and pulsed Doppler. We
      performed a control TEE in 7 patients in the electrical group and 6 in the
      amiodarone group, with no significant clinical differences between both groups. A
      second TEE was performed immediately in the 7 patients with successful electrical
      cardioversion. The peak flow velocities in the appendage before and after the
      procedure were: filling 43.3 +/- 22 vs 27.7 +/- 28 cm/sec (P = 0.01) and emptying
      35.5 +/- 22 vs 23.6 +/- 17 cm/sec (P = 0.01), respectively. The spontaneous echo
      contrast increased in 4 of the 7 patients. In 4 patients of the amiodarone group,
      the peak flow velocities in the appendage during AF and within the first 24 hours
      after restoration of sinus rhythm were: filling 37.4 +/- 12 vs 37.8 +/- 18 cm/sec
      and emptying 36.4 +/- 18 vs 35.9 +/- 18 cm/sec, respectively (P = NS). There was
      no change in spontaneous echo contrast. In conclusion, patients with AF reverted
      to sinus rhythm using amiodarone did not show changes in left atrial mechanical
      function; however, patients with electrical cardioversion showed mechanical
      dysfunction. Further investigations on the effects of amiodarone and other drugs
      on the mechanical function of the atria are needed to determine if patients
      reverted pharmacologically require anticoagulation post reversion.
      (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442916
TI  - Prosthetic Aortic Valve Thrombosis Detected by Doppler Echocardiography.
AB  - Thrombosis of the prosthetic valve is a highly lethal medical emergency that
      requires immediate diagnosis and prompt therapy. Establishing the diagnosis may
      be difficult, despite numerous physical, echocardiographic, fluoroscopic, and
      angiographic signs, which have been described. We report a case of prosthetic
      aortic valve thrombosis diagnosed by Doppler echocardiography. (ECHOCARDIOGRAPHY,
      Volume 13, March 1996)

PMID- 11442917
TI  - Doppler Echocardiography During Pregnancy: Physiological and Abnormal Findings.
AB  - Despite continuous improvements in diagnostic cardiology techniques,
      echocardiography remains the cornerstone for noninvasive cardiovascular
      assessment of the pregnant woman with heart disease or suspected cardiac
      abnormality. Reversible physiological cardiac remodeling of pregnancy associated
      with changes in valve patency or transvalvular flow pattern can be suitably
      assessed by the complementary use of quantitative pulsed- and continuous Doppler
      and qualitative color Doppler technology. These techniques are also useful for a
      better understanding of the pathophysiology of the hemodynamic consequences of
      fixed valve stenosis during pregnancy with respect to the labile nature of
      gradients resulting from variable loading conditions as occurs during pregnancy.
      Recent and specific areas of clinical use including cardiac output estimation,
      contrast echocardiography minimizing radioscopy during cardiac catheterization,
      and transesophageal echocardiography for selection of patients with mitral
      stenosis suitable for percutaneous catheter valvotomy illustrate the large
      spectrum of capabilities of this versatile method during pregnancy.
      (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442918
TI  - A Form Fruste of Shone's Complex Diagnosed by Transesophageal Echocardiography.
AB  - Shone's complex is a developmental complex of parachute mitral valve,
      supravalvular ring of the left atrium, subaortic stenosis, and coarctation of the
      aorta. Little clinical experience has been accumulated since the original
      description by Shone et al. This may be due to underrecognition of the condition
      by transthoracic echocardiography (TTE). We describe a forme fruste of Shone's
      complex which is definitively diagnosed only after precise demonstration of the
      anatomy by transesophageal echocardiography (TEE). Demonstration of these
      abnormalities by TEE was of little clinical significance in our patient, but may
      be important in others in whom prior TTE has been suboptimal. (ECHOCARDIOGRAPHY,
      Volume 13, March 1996)

PMID- 11442919
TI  - Early Recurrence of Malignant Fibrous Histiocytoma of the Heart.
AB  - Malignant fibrous histiocytoma is a pleomorphic soft tissue sarcoma, which
      constitutes only 2% of all cardiac malignancies and is typically located in the
      left atrium. We report a young male patient with malignant fibrous histiocytoma
      located on the right side of the heart. Early recurrence was observed after
      extensive surgical resection to relieve symptoms of outflow tract obstruction.
      Noninvasive evaluation and management with regard to the literature are
      discussed. (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442920
TI  - Usefulness of Transesophageal Echocardiography in Diagnosing and Guiding Correct
      Placement of a Right Ventricular Assist Device Malpositioned in the Left Atrium.
AB  - In this report, we describe how transesophageal echocardiography was used not
      only to diagnose incorrect cannula position of a right ventricular assist device
      in the left atrium through a patent foramen ovale, but also to guide and to
      confirm correct cannula placement. (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442921
TI  - Pushing Echocardiography Past the Aortic Root.

PMID- 11442922
TI  - Congenital Anomalies of the Aortic Arch.
AB  - Congenital anomalies of the aortic arch can occur either in isolation or in
      conjunction with other intracardiac defects. This review will examine congenital
      aortic arch anomalies as if they occur in isolation, with the awareness that
      intracardiac defects often coexist. The three general classes of abnormalities to
      be reviewed are: (1) abnormal connections between the aorta and pulmonary
      arterial system; (2) aortic arch obstructions; and (3) defects in the formation
      of the aortic arch typified by right aortic arches, vascular rings, and cervical
      aortic arches. (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442923
TI  - Magnetic Resonance Imaging of the Thoracic Aorta.
AB  - Magnetic resonance imaging (MRI) is well-suited for imaging the vascular system
      and is of particular value in assessing the anatomy and pathologies of the
      thoracic aorta. The intrinsic contrast between the blood pool and the vascular
      structures allows excellent depiction of intra- and extravascular anatomy and
      eliminates the need for intravenous contrast agents. A large field of view
      provides a complete evaluation of the mediastinum and chest. Both qualitative and
      quantitative techniques are available, which can yield physiological data in
      addition to anatomical information. The multiplanar capability offers images in
      any plane, allowing an accurate assessment of the longitudinal extent of disease
      and providing images perpendicular to vessels, even when tortuous. MRI currently
      represents an essential component of the imaging strategies available to assess
      the thoracic aorta and may come to function as a gold standard for certain
      conditions. As the technology continues its rapid evolution, MRI will most likely
      be able to serve as an effective noninvasive evaluation to provide all of the
      anatomical, pathological, and physiological information required of a
      comprehensive examination of the thoracic aorta. (ECHOCARDIOGRAPHY, Volume 13,
      March 1996)

PMID- 11442924
TI  - Ultrasonic Evaluation of the Abdominal Aorta.
AB  - Ultrasound is a very accurate and cost-effective method for evaluating the aorta
      and identifying abdominal aortic aneurysms. It is also valuable for following
      aneurysms for expansion. In the future, the use of color flow Doppler imaging may
      further prevent the risk of rupture by identifying specific high risk flow
      patterns. (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442925
TI  - Imaging Modalities in the Diagnosis of Acute Aortic Dissection.
AB  - The management of patients with acute aortic dissection requires a rapid
      diagnosis and precise information about the localization and extent of the
      dissection. Four imaging techniques are currently available to diagnose aortic
      dissection: aortography; contrast-enhanced computerized tomography (CECT);
      magnetic resonance imaging (MRI); and transesophageal echocardiography (TEE). All
      of these techniques have their specific advantages and inherent limitations.
      Recent studies have demonstrated that MRI may best provide a comprehensive and
      detailed evaluation of the thoracic aorta, therefore proposing this technique as
      a "new gold standard" in the diagnosis of acute aortic dissection. TEE, however,
      may be the best alternative technique, as it combines high sensitivity and
      specificity with high practicality. The practicality is particularly important in
      hemodynamically unstable patients in whom a rapid bedside imaging modality is
      required. CECT might be necessary in selected cases in whom TEE fails to provide
      a definite diagnosis. Aortography may be necessary in patients in whom clinical
      signs are suggestive of organ ischemia and in whom coronary anatomy needs to be
      delineated before operation. (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442926
TI  - Thoracic Aortic Aneurysms: Role of Echocardiography.
AB  - This article describes the evolving role of echocardiography for the detection
      and evaluation of thoracic aortic aneurysms. A brief summary of the clinical,
      anatomical, and pathological features of the etiologic categories of thoracic
      aneurysms is presented. The advantages and limitations of echocardiography and
      its comparison with other techniques (computed tomographic scanning, magnetic
      resonance imaging, and aortography) are discussed. (ECHOCARDIOGRAPHY, Volume 13,
      March 1996)

PMID- 11442927
TI  - Transesophageal Echocardiography in Thoracic Aortic Atherosclerosis.
AB  - Transesophageal echocardiography opened a new window to the thoracic aorta and
      for the first time permitted in vivo imaging of aortic atherosclerotic disease.
      The technique is useful in assessing the extent of the disorder, its
      complications, and possible treatment modalities. It will also be useful in the
      assessment of the progression as well as the possible regression of the disorder
      with appropriate (dietary or chemical) therapy. (ECHOCARDIOGRAPHY, Volume 13,
      March 1996)

PMID- 11442928
TI  - Transesophageal Echocardiography in the Evaluation of Aortic Trauma.
AB  - Transesophageal echocardiography (TEE) is superior to other imaging techniques
      for the diagnosis of aortic trauma. It can accurately, rapidly, and safely
      diagnose life-threatening conditions such as aortic rupture, pseudoaneurysm,
      traumatic aortic dissection, and intramural hematoma. TEE is useful for the
      diagnosis and prevention of iatrogenic aortic trauma induced by cardiovascular
      surgery, intraaortic procedures, and cardiopulmonary resuscitation.
      (ECHOCARDIOGRAPHY, Volume 13, March 1996)

PMID- 11442929
TI  - Severity of Aortic Regurgitation Assessed by Digital Image Processing of Doppler
      Spectral Recordings.
AB  - Visual estimates of the intensity of the regurgitant signal (RS) obtained by
      continuous-wave (CW) Doppler has been used as an indicator of the severity of
      aortic regurgitation (AR). This study was designed to test this concept
      quantitatively using digital image processing methods. Twenty-one patients with
      AR were studied, 14 of whom had concomitant mitral valve disease. Patients with
      aortic stenosis were excluded. By angiography, 10 patients had mild (grade 1 or
      2), 5 had moderate (grade 3), and 6 severe (grade 4) AR. We digitized three well
      defined AR envelopes and calculated the mean pixel intensity (MPI) of the RS and
      the systolic flow signal (SFS) using an offline computer analysis system
      developed in our laboratory. To negate the effects of different gain settings,
      the ratio of RS to SFS (RS/SFS ratio) was compared to angiographic grade of AR.
      Thus, each patient served as his own control. The mean RS/SFS ratio was 0.54 +/-
      0.42 SD (range 0.46-0.59) for mild AR, 0.76 +/- 0.71 SD (range 0.65-0.82) for
      moderate AR, and 0.84 +/- 0.52 (range 0.77-0.92) for severe AR. This RS/SFS ratio
      correlated well with angiographic severity of AR (r = 0.9). A ratio of <0.6
      identified patients with mild AR and >0.6 correlated with moderate-to-severe AR.
      We conclude that the ratio of the regurgitant to systolic flow CW Doppler signal
      is an accurate noninvasive indicator of AR severity. (ECHOCARDIOGRAPHY, Volume
      13, May 1996)

PMID- 11442930
TI  - Significance of "Strands" on Mitral Mechanical Prostheses During Late Follow-Up
      After Surgery.
AB  - The presence of "strands" on mitral mechanical prostheses (MMP) has been
      described, although their significance has yet to be established. The aim of this
      study was to determine the incidence and clinical implications of "strands" on
      MMP in late follow-up by a retrospective analysis of 320 consecutive patients who
      had undergone a transesophageal echocardiographic (TEE) examination under
      standardized conditions 7 +/- 6 years after mitral surgery. Twenty patients
      (6.25%) with "strands," defined as highly mobile linear echogenic densities, were
      identified. This group was compared with a control group of 38 patients, matched
      for age, sex, and interval between surgery and TEE study, selected at random from
      this population. Patients with MMP dysfunction were excluded. Type of prosthesis,
      echographic characteristics (left atrial diameter, spontaneous echo contrast,
      ejection fraction), and anticoagulant status were not found to bear any
      relationship to the presence of strands. However, the prevalence of previous
      embolic events was significantly higher in the "strand" group (10/20 [50%]) than
      in the control group (7/38 [18.4%]) (P < 0.05). The "strand" group also contained
      more patients with a prior history of mitral prosthesis thrombosis (7/20 [35%] vs
      1/30 [2.6%]; P < 0.05). However, long-term follow-up (1-4 years) was uneventful.
      These results suggest that: (1) in late follow-up, strands are rare in patients
      with MMP (6%); and (2) strands were related to previous thromboembolic episodes.
      (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442931
TI  - On-Line Myocardial Tissue Characterization with a New Commercially Produced
      Software.
AB  - Myocardial tissue characterization has been performed using various ultrasonic
      techniques, one of which is the cyclic variation of integrated backscatter, a
      method that analyzes the acoustic properties of the myocardium using
      backscattered radiofrequency signals to provide information about myocardial
      structure and function. Previous studies using prototype equipment have
      demonstrated a reduction in the cardiac cycle variation of integrated backscatter
      in various pathologic states. Recently, a commercially produced software package
      that allows online analysis of cyclic variation of integrated backscatter has
      been made available for testing by various investigators. To evaluate this new
      commercially produced software, we compared integrated backscatter results in
      three groups of patients: a control group; an end-stage cardiomyopathy group; and
      a heart transplant recipient group. Integrated backscatter of the septum and
      posterior walls in the parasternal long axis and 12, 3, 6, and 9 o'clock regions
      in the short axis was performed using a commercially produced program (Hewlett
      Packard Sonos 1500). In the control group, the mean cyclic variation of
      integrated backscatter was 5.04 +/- 1.60 dB in the septum and did not
      significantly vary from the rest of the regions studied. In comparison, cyclic
      variation of integrated backscatter in every region studied was reduced in the
      cardiomyopathy and heart transplant groups. Intraobserver variability,
      interobserver variability, and reproducibility over a 3-month interval was found
      to be 6.5%, 5.7%, and 7.5%, respectively. These results indicate that: (1) online
      analysis of cardiac cyclic variation of integrated backscatter is possible
      utilizing commercially produced software; (2) results obtained are consistent
      with a low intraobserver and interobserver variability and are reproducible over
      time; and (3) as observed in the comparison between the transplant and control
      groups, this information may detect changes in cardiac structure even in the
      absence of changes in function. (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442932
TI  - Supine Bicycle Exercise Echocardiography: A Potent Immediately Available Tool for
      Detection and Localization of Myocardial Ischemia for the Initial Cardiologist.
AB  - BACKGROUND: Exercise echocardiography (EE) is being used increasingly as an
      investigative technique now that dynamic images can be captured digitally. Its
      equivalent reliability with scintigraphic methods has been demonstrated in a
      hospital setting. This study analyzes its impact on daily practice. MATERIALS AND
      METHODS: Standardized progressive stress was produced by supine bicycle
      ergometry. Echocardiographic images of complete cardiac cycles were obtained in
      standard apical and parasternal short-axis views before, during, and after
      maximum effort, and digitized for simultaneous analysis of synchronized images at
      rest and during exercise. Two hundred sixteen patients (175 men and 41 women;
      mean age 58 +/- 10 years) were studied. RESULTS: Image quality was suboptimal in
      4 cases. In the remaining 212 cases, ischemia was detected in 91 cases, and the
      test was negative in 114 cases and doubtful in 7 cases. Control by selective
      coronary angiography, as indicated by the clinical situation, was performed in 52
      cases. In this particular group, EE showed 87% sensitivity, which is
      significantly higher than the 59% recorded for conventional exercise testing (P <
      0.0001). CONCLUSIONS: EE by bicycle ergometer in the supine position is a valid,
      noninvasive investigative technique that can be used in an outpatient situation
      (feasibility 95%) since it is readily available. Its value appears to be greatest
      in cases in which exercise ECG is not conclusive. A negative result enables the
      initial cardiologist to reassure the patient immediately, which has been
      demonstrated in the literature to have favorable prognostic value.
      (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442933
TI  - Pericardial Tamponade: A Manifestation of Pericardial Sac Sarcoma-A Case Report.
AB  - Cardiac tamponade was manifested in a 30-year-old male with a 6-month history of
      fever and weight loss prior to admission. Cross-sectional echocardiography
      demonstrated huge pericardial effusion with a large mass in the posterior
      pericardial space. Pericardiocentesis revealed exudative fluid with no malignant
      cells. Surgery performed to determine the nature of the mass disclosed the mass
      originating from the posterior pericardium, invading the posterior pleural sac
      and adjacent structures. Histopathology identified spindle cell sarcoma. The
      preoperative diagnosis of the mass and its presenting features and nature are
      discussed. (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442934
TI  - Left Ventricular Thrombus After Pregnancy: Choice of Surgical Access Using
      Dynamic Three-Dimensional Echocardiography.
AB  - Two idiopathic thrombi loosely attached to the left ventricular wall were
      detected by dynamic three-dimensional echocardiography. Because the thrombi were
      shown to be lobulated and extremely mobile, urgent surgical treatment was
      mandatory. Three-dimensional image reconstruction enhanced appreciation of left
      ventricular thrombi by enabling accurate imaging of the spatial relationship
      between the thrombus, the myocardial wall, and the valvular apparatus, so that
      the most advantageous surgical access could be chosen. (ECHOCARDIOGRAPHY, Volume
      13, May 1996)

PMID- 11442935
TI  - Nonsurgical Repair of Femoral Artery Pseudoaneurysm with Color Flow Guided
      Ultrasound Transducer Compression.
AB  - Arterial pseudoaneurysm is a significant complication following invasive
      angiographic procedures. A definitive diagnosis is usually obtainable with
      ultrasound imaging, including color flow Doppler. Treatment modalities include
      surgical repair or transducer directed compression. In our experience, 26 of 29
      patients (89.7%) with femoral artery pseudoaneurysm were successfully treated
      utilizing transducer directed compression. One pseudoaneurysm thrombosed
      spontaneously before the procedure was completed. No complications were
      encountered. Our experience suggests that surgical repair is not required for
      most femoral artery pseudoaneurysms. (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442936
TI  - Echocardiographic Features of Ventricular Septal Rupture with Right Ventricular
      Aneurysm After Acute Myocardial Infarction.
AB  - Postinfarction ventricular septal defect is a life-threatening disorder that may
      be adequately treated if the diagnosis is obtained promptly. Two-dimensional
      color Doppler echocardiography is a reliable tool for this diagnosis and gives
      additional information regarding its location, size, and shape. The authors
      emphasize the feasibility of this method to depict a particular form of
      postinfarction interventricular septal rupture, which developed an aneurysm
      inside the right ventricular cavity. Its characteristics were completely defined
      by color Doppler echocardiography and confirmed at surgery. (ECHOCARDIOGRAPHY,
      Volume 13, May 1996)

PMID- 11442937
TI  - Transesophageal Color Doppler Echocardiographic Diagnosis of Cardiac Rupture
      Following Acute Myocardial Infarction.
AB  - This report describes a case of cardiac rupture following acute myocardial
      infarction accurately diagnosed by transesophageal color Doppler
      echocardiography, which showed a very narrow transmural tract from the left
      ventricle into the pseudoaneurysm cavity. Such a small, slitlike rupture would
      most likely have been missed by an otherwise routine transesophageal examination,
      and we stress the importance of color Doppler interrogation in its accurate
      diagnosis. (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442938
TI  - Congenital Aortic Valve and Aortic Arch Anomalies: Part I.

PMID- 11442939
TI  - Noninvasive Evaluation of Aortic Valve Anatomy.
AB  - Although aortic valve anatomy is three-dimensionally complex, careful
      echocardiographic investigation can yield surgically relevant information. The
      promise of intravascular and transesophageal imaging is in yielding the raw data
      of sufficient resolution to make the three-dimensional reconstruction clinically
      meaningful. (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442940
TI  - Aortic Stenosis or Atresia with Associated Hypoplasia of the Left Ventricle:
      Imaging Before and After Reconstructive Surgery.
AB  - Aortic atresia or stenosis, when associated with hypoplasia of the left
      ventricle, presents the cardiac surgeon with a challenging reconstruction. Many
      preoperative and intraoperative decisions are now made on the basis of ultrasound
      data. Furthermore, echocardiography provides the most convenient way to time the
      stages of the reconstructive sequence and assess the hemodynamic result.
      (ECHOCARDIOGRAPHY, Volume 13, May 1996)

PMID- 11442941
TI  - Ultrasonic Imaging of Vascular Rings and Other Anomalies Causing Tracheobronchial
      Compression.
AB  - Display of aortic arch anatomy using single plane views does not readily allow
      for a three-dimensional interpretation of structural relationships. A method that
      includes a sweep consisting of multiple contiguous frontal planes has been
      developed for the evaluation of the arch sidedness and number, brachiocephalic
      vessel pattern, upper descending thoracic aorta sidedness, ductus arteriosi
      site(s), and proximal pulmonary arteries. The addition of Doppler color flow
      mapping aids in the tracing of multiple vascular structures in complex cases, and
      in assessing ductus arteriosi and arch patency. Posterior angulation can display
      encirclement of the air-filled trachea in cases of double aortic arch. Vascular
      ring segments without lumens cannot be displayed. (ECHOCARDIOGRAPHY, Volume 13,
      May 1996)

PMID- 11442942
TI  - Quantification of Mitral and Tricuspid Regurgitation Using Jet Centerline
      Velocities: An In Vitro Study of Jets in an Ambient Counterflow.
AB  - A method for quantifying mitral and tricuspid regurgitant volume that utilizes a
      measure of jet orifice velocity U(0) - m/sec), a distal centerline velocity (U(m)
      - m/sec), and the intervening distance (X - cm) was recently developed; where jet
      flow rate (Q(cal) - L/min) is calculated as Q(cal) = (U(m)X)(2)/(26.46U(o)). This
      method, however, modeled the regurgitant jet as a free jet, whereas many atrial
      jets are counterflowing jets because of jet opposing intra-atrial flow fields
      (counterflows). This study concentrated on the feasibility of using the free jet
      quantification equation in the atrium where ambient flow fields may alter jet
      centerline velocities and reduce the accuracy of jet flow rate calculations. A 4
      cm wide chamber was used to pump counterflows of 0, 4, and 22 cm/sec against jets
      of 2.3, 4.8, and 6.4 m/sec originating from a 2-mm diameter orifice. For each
      counterflow-jet combination, jet centerline velocities were measured using laser
      Doppler anemometry. For free jets (no counterflow), flow rate was calculated with
      98% mean accuracy. For all jets in counterflow, the calculation was less accurate
      as: (i) the ratio of jet orifice velocity to counterflow velocity decreased
      (U(o)/U(c), where U(c) is counterflow velocity), i.e., the counterflow was
      relatively more intense, and (ii) centerline measurements were made further from
      the orifice. But although counterflow lowered jet centerline velocities beneath
      free jet values, it did so only significantly in the jet's distal portion (X/D >
      16, i.e., >16 orifice diameters from the origin of the jet). Thus, the initial
      portion (X/D < 16) of a jet in counterflow behaved essentially as a free jet. As
      a result, even in significant counterflow, jet flow rate was calculated with >93%
      accuracy and >85% for jets typical of mitral and tricuspid regurgitation,
      respectively. Counterflow lowers jet centerline velocities beneath equivalent
      free jet values. This effect, however, is most significant in the distal portion
      of the jet. Therefore, regurgitant jets, although not classically free because of
      systolic atrial inflow or jet-induced intra-atrial swirling flows, will decay in
      their initial portions as free jets and thus are candidates for quantification
      with the centerline technique. (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442943
TI  - Impact of Beta Blockers on Dobutamine-Atropine Stress Echocardiography.
AB  - Dobutamine increases oxygen demand in the myocardium and is used in conjunction
      with echocardiography to detect coronary artery disease. Beta blockers (BB) are
      partial antagonists of dobutamine and, therefore, offset dobutamine effects.
      Still, the impact of BB therapy on dobutamine stress echocardiography is not
      clear. One hundred forty-one dobutamine-atropine echocardiographic studies have
      retrospectively been analyzed: 27 patients were on BB (19%; group I); and 114 off
      BB (81%; group II). Coronary angiography was performed in a similar percentage of
      patients (97% and 85%, respectively; P = NS). No differences in clinical and
      angiographic profile were found between the groups. Sensitivity (83% vs 71%; P =
      NS) and specificity (100% vs 95%; P = NS) for coronary artery disease were
      similar in both groups. Atropine was infused more frequently to patients from
      group I (67% vs 46%; P = 0.04). Limiting side effects and prolonged ischemia
      presented with the same frequency in both groups. When the dobutamine test was
      positive, severe extent of ischemia appeared more often in patients from group I
      than in patients from group II (66% vs 33%; P = 0.03). The majority of patients
      from group I (55%) with severe extent of ischemia and only 12% from group II
      received atropine (P = 0.02). No differences were found in dobutamine time and
      extent of ischemia in patients from group I who had a positive response to
      dobutamine. On the contrary, patients from group II with one vessel disease had a
      dobutamine time longer (10.5 +/- 3.8 vs 7.8 +/- 3.7 min; P < 0.05) and extent of
      ischemia smaller (1.8 +/- 0.4 vs 2.6 +/- 0.5 segments; P < 0.05) than patients
      from group II with multivessel disease. We conclude that: 1) sensitivity of
      dobutamine-atropine echocardiography for diagnosis of coronary artery disease
      remains even if patients are on BB; 2) patients with significant coronary artery
      disease who are taking BB often develop severe myocardial ischemia during
      dobutamine-atropine stress echocardiography; and 3) BB therapy precludes
      stratification of a positive echocardiographic response. These conclusions should
      be confirmed in a prospective study to be considered as definitive.
      (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442944
TI  - Relationship Between Intravascular Hemolysis and Bright Sparkling Echoes Detected
      by TEE in the Vicinity of Mechanical Mitral Prosthesis.
AB  - The significance of abnormal bright and sparkling echoes in patients with
      mechanical mitral prosthetic valves (MMPV) has yet to be established. In the
      present study, the incidence of this phenomenon and its relationship with
      hemolysis was evaluated. Thirty-five consecutive patients with MMPV, each
      examined by transesophageal echocardiography (TEE), were divided into four
      groups: (1) no bright echoes (n = 11 patients); (2) minor echoes (+) (n = 11
      patients); (3) moderate echoes (++) (n = 7 patients); and (4) numerous echoes
      (+++) (n = 6 patients). Hemolysis was evaluated from assays of serum haptoglobin,
      serum lactic dehydrogenase (LDH) and hydrobutyric dehydrogenase (HDH), plasma
      hemoglobin, indirect bilirubin, and LDH1 and LDH2 isoenzymes. Serum haptoglobin
      was significantly lower in the patients with bright echoes (0.17 vs 0.63; P <
      0.05). In patients with (++) and (+++) bright echoes, the plasma hemoglobin
      levels and indirect bilirubin levels were significantly higher than the levels
      found in those patients with minor echoes or with no echoes. These results
      suggest that bright echoes in patients with MMPV are related to intravascular
      hemolysis, and the more intense the echo the more severe the hemolysis.
      Furthermore, there was a higher incidence of bright echoes in the patients with
      bileaflet prosthetic valves than in those fitted with the Bjork valve (84.6% vs
      22%). (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442945
TI  - Echocardiographic Evaluation of Common Atrioventricular Canal Defects: A Study of
      206 Consecutive Patients.
AB  - An accurate echocardiographic evaluation of common atrioventricular canal (CAVC)
      requires in-depth knowledge of the wide spectrum of morphological and
      physiological variations in this group of anomalies. In order to evaluate the
      incidence and morphological distribution of AV canal defects in a large series of
      patients and to define a systematic approach to the echocardiographic
      examination, we reviewed the echocardiograms of 206 consecutive patients with
      CAVC studied at Texas Children's Hospital over a 32-month period. The complete
      form of CAVC was most common (68.4%) and presented at an earlier age (mean +/-
      SD: 1.6 +/- 2.4 months). A partial AV canal (ostium primum atrial septal defect
      [ASD]) was found in 42 patients (20.4%) and their age at presentation was higher
      (9.2 +/- 10 months). Twenty-three patients (11.2%) had a transitional AV canal.
      Down syndrome was diagnosed in 34% of patients, the majority of whom (79%) had a
      complete CAVC. Associated malformations were found in 46% of patients: anomalies
      of the conotruncus were most frequent (18%), followed by secundum ASD (14.1%),
      anomalous pulmonary venous connection (11.2%), and heterotaxy syndrome (11.2%).
      Subaortic obstruction and mitral stenosis were less common. The AV canal was
      unbalanced in 14.1% of patients, with the right ventricular dominant form being
      more common than the left ventricular dominant form (10.7% and 3.4%,
      respectively). Based on our experience, we developed a systematic, segment-by
      segment approach to the echocardiographic examination in infants with CAVC.
      Together with detailed anatomical information, Doppler evaluation provides
      crucial hemodynamic information that allows planning of surgical repair.
      (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442946
TI  - Spontaneous Microbubbles in Transit in the Right Cardiac Chambers.
AB  - We present two patients with echocardiographically detected small echoes passing
      through the right heart cavities, consistent with the clinical picture of
      thromboemboli. After anticoagulant treatment, pulmonary artery pressure fell and
      the echocardiographic picture of small echoes in transit disappeared. In the
      authors' opinion, the detected echoes passing through the right heart represented
      microthromboemboli in transit. (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442947
TI  - Rupture of Aortic Dissection During Attempted Transesophageal Echocardiography.
AB  - Transesophageal echocardiography (TEE) provides a rapid and accurate diagnosis in
      patients with dissection of the thoracic aorta. The procedure is considered to be
      safe. We report a case where rupture of a dissecting thoracic aneurysm occurred
      during attempted TEE in a patient, who had been clinically stable for 1 week. TEE
      was performed because aortic valve endocarditis was suspected, and the procedure
      did not include close surveillance of the blood pressure. Careful manipulation of
      the probe, adequate sedation, monitoring, and treatment of acute rises in blood
      pressure was recommended in patients with even a slight suspicion of dissection
      undergoing TEE. (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442948
TI  - Myocardial Stunning and Unique ECG Changes Associated with Dobutamine Stress
      Echocardiography.
AB  - The clinical, electrocardiographic, and echocardiographic changes associated with
      myocardial stunning during dobutamine stress echocardiography in a patient with
      severe left main coronary artery disease are presented. (ECHOCARDIOGRAPHY, Volume
      13, July 1996)

PMID- 11442949
TI  - Multiplane Transesophageal Echocardiographic Detection and Differential Diagnosis
      of Isolated Right Pulmonary Artery Agenesis.
AB  - We present a case report of isolated right pulmonary artery agenesis detected by
      multiplane transesophageal echocardiography (TEE). A special emphasis is placed
      on its important role in the differential diagnosis and hemodynamic and
      functional evaluation of patients with unilateral pulmonary oligemia on chest
      radiograph. We also present a case report of pulmonary embolism with complete
      obstruction of the right pulmonary artery for better understanding and for
      comparison of TEE images in patients with pulmonary artery agenesis.
      (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442950
TI  - Ultrasonic Tissue Characterization: Review of a Noninvasive Technique for
      Assessing Myocardial Viability.
AB  - The determination of myocardial perfusion and myocardial viability has prognostic
      and therapeutic implications, particularly in the current era of percutaneous
      transluminal coronary angioplasty and thrombolytic therapy. Several modes of
      investigation, including positron emission tomography, thallium-201 scintigraphy,
      and nuclear magnetic resonance imaging are used to differentiate viable from
      nonviable myocardium. Though these noninvasive tests are useful diagnostic
      modalities, they are expensive, time consuming, and too cumbersome to be used in
      the acute setting. Expeditious distinction between viable and nonviable
      myocardium, during acute coronary syndromes, is of great importance since
      reperfusion can minimize the extent of ischemic injury and infarction. An
      expanding body of evidence confirms that ultrasonic tissue characterization has
      great potential to become a practical bedside diagnostic tool in the search for
      salvageable myocardium. Further clinical investigative studies would help
      accomplish a better understanding of the complex interaction between ultrasound
      and myocardium. (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442951
TI  - Flail Aortic Valve in Systemic Lupus Erythematosus: Diagnosis by Transesophageal
      Echocardiography.
AB  - This case report describes a patient with systemic lupus erythematosus who
      demonstrated by transesophageal echocardiography (TEE) a flail right coronary
      cusp of the aortic valve causing severe aortic regurgitation. This finding was
      confirmed at surgery, which showed near detachment of the right coronary leaflet
      near the commissure. Destruction of areas of the aortic valve has been reported
      in one previous case report in the absence of infective endocarditis or a
      traumatic process. This is the second case to our knowledge and the first to
      describe identification by TEE. (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442952
TI  - Isolation of the Left Innominate Artery.
AB  - Isolation of the left innominate artery is a rare anomaly associated with a right
      aortic arch. Presented here is a case of a 3-day-old infant with an isolated
      innominate artery along with d-transposition of the great arteries, and a ductal
      dependent circulation. These two lesions have not previously been reported
      together. (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442953
TI  - Transesophageal Echocardiographic Imaging for Congenital Lesions of the Left
      Ventricular Outflow Tract and the Aorta.
AB  - A comprehensive transthoracic echocardiographic imaging is possible for most
      pediatric patients. However, for patients in whom accurate anatomical and
      physiological assessment is not possible, transesophageal echocardiography (TEE)
      provides a supplemental diagnostic modality. Imaging the left ventricular outflow
      tract and the aorta involves a complicated technique of rotation, flexion, and
      changes in the depth of the transesophageal probe because the areas of
      interrogation involve multiple planes within the thoracic cavity. Furthermore,
      the relationship between the esophagus and the cardiovascular structures changes
      at various levels of the thorax. Transesophageal probes having characteristics of
      frequency agility, all forms of Doppler capability, and a higher number of
      crystal elements are now available. Abnormalities of the subaortic area, the
      aortic valve, coronary arteries, and the entire thoracic aorta can be clearly
      demonstrated. TEE also has played a complementary role in diagnostic and
      interventional catheterization. It has become vital in the operating room for the
      preoperative definition of certain aspects of the anatomy and for immediate
      postoperative evaluation of the result of surgery. (ECHOCARDIOGRAPHY, Volume 13,
      July 1996)

PMID- 11442954
TI  - The Value of Aortic Valve and Aortic Arch Imaging in the Identification of
      Genetic Syndromes.
AB  - Echocardiographers imaging the aortic valve, root, and arch may observe
      coincidental extracardiac malformations, unusual facial features or body habitus,
      and/or mental or growth retardation. The pattern of anomalies may indicate a
      previously unrecognized genetic malformation syndrome. Echocardiographers also
      encounter genetic syndromes when clinicians specifically refer patients with
      certain syndromes for prospective detection of cardiac anomalies. Although aortic
      valve, root, and arch anomalies occur in a large number of syndromes, this
      article will focus on the most distinctive associations. In addition to
      discussing structural congenital cardiovascular malformations, aortic root
      dilation occurring in inherited disorders of connective tissue will be included.
      (ECHOCARDIOGRAPHY, Volume 13, July 1996)

PMID- 11442955
TI  - Antibiotic Prophylaxis for Endocarditis Prevention During Transesophageal
      Echocardiography: Controversy, Consideration, and What Really Happens.
AB  - A survey was conducted in order to gain a better understanding of actual practice
      policies followed by academically affiliated institutions regarding the use of
      prophylactic antibiotics during transesophageal echocardiography. Results
      revealed that 10 of the 20 centers routinely used intravenous antibiotic
      prophylaxis for high risk transesophageal echocardiography. However, 5 of the 20
      centers did not use any prophylactic antibiotics routinely, and the remaining 5
      centers used primarily oral prophylactic regimens. In addition, the type of
      patient that was considered high risk for which antibiotic prophylaxis was used
      differed among institutions. Practice guidelines in 4 of the 20 institutions have
      changed in the last 5 years. These findings demonstrate a wide variation in the
      actual practice policies of different institutions, probably reflecting, in part,
      the lack of convincing evidence that prophylactic antibiotics benefit this
      subgroup of patients. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442956
TI  - Reduced Left Ventricular Contractile Reserve Identified by Low Dose Dobutamine
      Echocardiography as an Early Marker of Cardiac Involvement in Asymptomatic
      Patients with Thalassemia Major.
AB  - Patients with beta thalassemia major present with severe anemia and need
      continuous transfusion therapy. The consequent iron overload leads to
      hemochromatosis. Initial cardiac involvement can be present in thalassemic
      patients without clinical manifestations of heart failure. The purpose of this
      study was to assess the contractile reserve of the left ventricle in patients
      with normal baseline two-dimensional (2-D) echocardiographic findings using low
      dose dobutamine echocardiography. The underlying hypothesis was that, at an early
      stage, structural impairment of the myocardial wall due to myocardial iron
      deposits and/or secondary fibrotic changes could be so subtle so as not to impair
      resting systolic function, but is severe enough to blunt or even exhaust the
      contractile response to inotropic stimulation. Twenty-four consecutive patients
      (13 men and 11 women; ages 18 +/- 3.8 years) with beta thalassemia major
      undergoing evaluation for bone marrow transplantation entered the study. By
      selection, all were asymptomatic, without clinical signs of cardiac failure, and
      had normal regional and global systolic function at baseline echocardiographic
      study. A control group of 16 age and sex matched subjects was also studied. All
      underwent baseline, 2-D, and Doppler study, as well as dobutamine stress (up to 5
      &mgr;g/kg per min) 2-D echocardiographic study. Patients and controls showed
      comparable values of indexes of global (ejection fraction: 0.64 +/- 0.06 vs 0.65
      +/- 0.05, P = NS) and regional (systolic thickening of posterior wall: 90 +/- 34
      vs 91 +/- 34%, P = NS) function at baseline. Left ventricular diastolic filling
      was evaluated with Doppler echocardiography. Peak flow velocity in early diastole
      was increased in thalassemic patients compared to controls (114 +/- 16 vs 96 +/-
      18 cm/sec, P < 0.01), and flow velocity deceleration time was reduced (139 +/- 17
      vs 157 +/- 20 msec, P < 0.01). At peak dobutamine, thalassemic patients showed a
      blunted contractile response compared to controls for indexes of both global
      (ejection fraction: 0.62 +/- 0.06 vs 0.69 +/- 0.05, P < 0.01) and regional (%
      systolic thickening of posterior wall: 91 +/- 36 vs 130 +/- 39%, P < 0.01)
      function. When individual patient analysis was performed, echocardiographic
      parameters were beyond the 95% confidence limits obtained from normal controls in
      5 (21%) of the 24 study patients by one or more Doppler diastolic indexes, in 6
      (25%) by indexes of contractile reserve, and in 11 (46%) by one of either
      diastolic function or contractile reserve indexes. These data demonstrate that
      the "iron heart" of asymptomatic thalassemic patients is a weak heart. Even if
      the regional and global systolic functions are similar to normals under resting
      conditions, the application of an inotropic challenge unmasks the weakness of
      these hearts, which can be identified at an earlier stage of their natural
      history through the blunted contractile response following the infusion of low
      dose dobutamine. The information on contractile reserve is not redundant, but
      rather incremental and in addition to that provided by Doppler echocardiographic
      indexes, which may be abnormal in these patients. (ECHOCARDIOGRAPHY, Volume 13,
      September 1996)

PMID- 11442957
TI  - Is a Full Digital Echocardiography Laboratory Feasible for Routine Daily Use?
AB  - To determine the feasibility and accuracy of digital echocardiography for routine
      interpretation of two-dimensional and Doppler echocardiography, we studied 93
      consecutive patients chosen at random from our daily workload. The parameters
      studied included cavity sizes, biventricular regional and global systolic and
      diastolic function, valvular structure and function, and presence or absence of
      pericardial disease. The results were first interpreted using quad screen,
      digital format cine loops. These results were then compared with the results
      obtained from reviewing the video-tape images. Seventy-nine patients (87%) showed
      complete concordance between the digital system and video tape. Among the 1156
      echocardiographic parameters/measurements examined in all patients, a 99%
      concordance rate (normal vs abnormal) was found. Disagreements between the
      digital system and video tape in the patients undergoing two-dimensional/Doppler
      exams included mitral valve prolapse in 3, mild valvular insufficiency in 5, a
      small pleural effusion in 2, and a wall-motion abnormality in 3 patients. In
      conclusion, the use of digital technology for evaluation of routine
      echocardiograms appears to compare favorably with the interpretation of images
      using the conventional video tape. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442958
TI  - Peripheral Artery Pseudoaneurysm: Treatment by Transcutaneous Compression Guided
      by Ultrasonography.
AB  - Pseudoaneurysm is a well-recognized complication of invasive arterial procedures
      that is easily diagnosed with ultrasound. While most pseudoaneurysms will be
      resolved spontaneously within 3 months, some may lead to limb swelling, ischemia,
      thromboembolism, or nerve damage. To forestall such complications, we attempted
      to close the lesion using ultrasound to guide application of pressure in 13
      patients with pseudoaneurysms following arterial catheterizations. Successful
      closure averaged 64 minutes (range 20-180) with successful results achieved in 11
      (85%) of the 13 patients. No complications followed the application of either
      manual or device-assisted pressure. We conclude that transcutaneous compression
      is a generally safe and successful treatment of uncomplicated pseudoaneurysm and
      should be used as the treatment of choice for this lesion. (ECHOCARDIOGRAPHY,
      Volume 13, September 1996)

PMID- 11442959
TI  - Ultrasound Densitometric Analysis: Comparison Between an Online Digital
      Acquisition Acoustic Program and an Offline Analog Program.
AB  - Videodensitometric analysis of myocardial contrast echocardiography is
      traditionally performed off line. Recently, an online contrast ultrasound
      analysis system, Acoustic Densitometry (Hewlett-Packard), was introduced. We
      compared pixel intensities acquired with Acoustic Densitometry to pixel
      intensities derived from videodensitometry. A tissue phantom was imaged in phase
      I using three transducer frequencies (2.5, 3.5, and 5.0 MHz). In phase II, an in
      vitro flowing tube model with various concentrations of Albunex(R) was imaged at
      two flow rates, 0.6 and 1.2 m/sec, and at two transducer frequencies, 2.5 and 3.5
      MHz. The relationship between pixel intensities yielded by the two systems for
      identical ultrasound signals was determined with linear regression. Intensities
      derived with Acoustic Densitometry strongly correlated with those derived from
      the offline videodensitometry system. The intensities were related by a
      predictive multiplicative factor based on display characteristics of the two
      systems. These results suggest that semiquantitative, online perfusion analysis
      with Acoustic Densitometry is as sensitive as analysis offline with
      videodensitometry. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442960
TI  - Echocardiographic Findings in Rupture of Long False Tendons: Report of Two Cases.
AB  - Long left ventricular false tendons, which connect distant sites on the
      ventricular endocardium, are common incidental echocardiographic findings. We
      describe two cases in which rupture of such long false tendons produced unusual,
      highly mobile, intracavitary echo densities that could be mistaken for other
      important pathologies, such as thrombus or vegetation. The differentiation of
      ruptured long false tendons and intact short apical false tendons from other
      entities they may mimic is described. (ECHOCARDIOGRAPHY, Volume 13, September
      1996)

PMID- 11442961
TI  - Transesophageal Three-Dimensional Echocardiographic Assessment of Normal and
      Stenosed Coronary Arteries.
AB  - We describe our preliminary experience in assessing normal and stenosed coronary
      arteries using transesophageal three-dimensional echocardiography (3-D echo) in
      27 adult patients. Multiplane transesophageal two-dimensional images of the
      coronary arteries (20 left, 3 right, 3 both left and right, and 1 posterior
      descending) were first acquired in the TomTec computer in 3 degrees sequential
      increments, from 0 degrees to 180 degrees, and then 3-D reconstruction was
      performed. The entire left main (LMC, measuring 0.5 to 1.7 cm, mean 1.0 cm) as
      well as variable lengths of proximal or both proximal and middle segments of the
      left anterior descending (LAD, measuring 0.2 to 2.5 cm, mean 0.8 cm) and
      circumflex (LCX, measuring 0.2 to 2.8 cm, mean 0.9 cm) coronary arteries together
      with some of their branches could be visualized in 3-D in 22 of 23 patients. In
      the remaining patient, the LMC was absent, and both LAD and LCX could be
      visualized in 3-D as having separate but adjacent origins from the left sinus of
      Valsalva (proven by angiography). In two patients, long segments of
      interventricular and great cardiac veins were also visualized accompanying the
      LAD and LCX, respectively. The right coronary artery (RCA, measuring 0.7 to 3.0
      cm, mean 1.9 cm) was also successfully delineated in 3-D in all six patients in
      whom an attempt was made to visualize it during echo examination. Using the
      transgastric approach, a long (1.8 cm) segment of the posterior descending branch
      (PDA) of RCA was imaged in one patient. In addition, nine significantly stenotic
      lesions (>50% lumen diameter) were identified by 3-D in eight patients involving
      LMC (1), proximal LAD (1), mid LAD (1), proximal LCX (2), proximal RCA (3), and
      mid PDA (1). Eight of these 9 lesions were confirmed by coronary angiography. The
      remaining lesion (mid PDA) could not be confirmed since the patient did not
      undergo angiography. Our preliminary study demonstrates the usefulness of
      transesophageal 3-D echo not only in delineating normal coronary arteries but
      also diagnosing significant atherosclerotic stenosis in these vessels.
      (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442962
TI  - Doppler Detection of Cerebral Emboli.

PMID- 11442963
TI  - Cerebral Embolism as a Cause of Stroke and Transient Ischemic Attack.
AB  - The most frequent cause of stroke and transient ischemic attacks is cerebral
      embolism. Cardiogenic cerebral embolization is common among patients with any
      cause of atrial fibrillation (AF) but particularly in AF resulting from rheumatic
      and arteriosclerotic heart disease. Rare causes of cerebral embolism include fat
      entering the bloodstream after trauma, tumor cells arising from atrial myxomata,
      and gas embolism. Cerebral embolic infarctions and their sources of origin can
      now be confirmed during life by many invasive (I) and noninvasive (NI) procedures
      including computerized tomography (CT) scanning (NI), magnetic resonance imaging
      (MR) (NI), contrast angiography (I), digital subtraction angiography (I),
      magnetic resonance angiography (NI), carotid Doppler and transcranial Doppler
      (NI), and echocardiography (NI) without and with contrast. These tests visualize
      the following: embolic occlusions of small and large cerebral arteries, resultant
      cerebral infarctions in appropriate vascular territories, plaques within the
      aorta, subclavian, vertebral, and carotid arteries, and mural thrombi located
      within the heart and aortocephalic arteries. Transcranial Doppler monitoring of
      the middle cerebral artery detects both small (asymptomatic) and large
      (symptomatic) cerebral emboli, as well as transseptal cardiac shunting, which is
      a cause of paradoxical embolization. Holter monitoring detects episodic cardiac
      dysrhythmias not apparent during routine ECG. CT or MRI identify cerebral
      infarctions resulting from virtually all large cerebral emboli. Early recognition
      and identification of types of cerebral embolism are important because of the
      availability of effective prophylactic therapies. (ECHOCARDIOGRAPHY, Volume 13,
      September 1996)

PMID- 11442964
TI  - Detection of Embolism with Doppler Ultrasound: A Review.
AB  - Doppler detection of venous and arterial gas emboli has been recognized since
      1968. The technology has been applied using 5-MHz ultrasound to study
      decompression sickness and monitor cardiopulmonary bypass and intracranial
      surgery. Since the advent of transcranial Doppler, which requires the use of
      lower ultrasonic carrier frequencies to penetrate the temporal bone, the
      detection of particulates moving in the bloodstream has been available. Using 2
      MHz, microembolic signals have been detected in a variety of clinical situations,
      including cardiac conditions known to have high probabilities to produce embolic
      stroke. The basic features of a Doppler embolic signal have been clarified, and
      many investigators are applying the technology to determine the clinical
      significance of the detected emboli and their use in diagnosis and medical and
      surgical treatments. The basis for automatic sizing, counting, and characterizing
      the emboli is under development. The applications of Doppler detection of emboli
      will range from diagnosis and localization of embolic sources to improvement in
      surgical techniques and adjustments in medical treatments. (ECHOCARDIOGRAPHY,
      Volume 13, September 1996)

PMID- 11442965
TI  - Microembolism in Carotid Artery Disease.
AB  - Abnormal high intensity transient signals detectable with transcranial Doppler
      (TCD) sonography have been associated with formed cerebral microembolism. Using
      long-term TCD monitoring, these clinically silent microembolic events can be
      observed in patients with cerebrovascular disease. Downstream of high grade
      internal carotid artery (ICA) stenosis, they occur significantly more frequently
      in neurologically symptomatic than in asymptomatic patients. Although the
      occurrence of microemboli is random, the individual rate underlies circadian
      fluctuations and seems to decline within the first weeks after an ischemic event.
      Pathoanatomic work suggests that luminal ulcer and thrombosis of the stenosed ICA
      are the major sources of microemboli. Thus, by tapping into an important
      pathomechanism, the detection of clinically silent cerebral microembolism appears
      to provide paraclinical evidence of "unstable carotid artery disease" and may
      help to evaluate more specific treatment strategies. (ECHOCARDIOGRAPHY, Volume
      13, September 1996)

PMID- 11442966
TI  - Microembolism in Cerebral Angiography.
AB  - Using transcranial Doppler monitoring of middle cerebral artery blood flow
      velocity, a number of studies have detected transient high intensity embolic
      signals during cerebral angiography. These are particularly frequent during
      contrast injection, but also sometimes occur at the time of catheter and wire
      manipulations and following saline flushes. These embolic signals appear to be
      asymptomatic, although a correlation with subtle neurological damage, by
      neuropsychological evaluation for example, has not been made. Experimental
      studies in flow models and animal models suggest that the majority of these
      signals represent air emboli. These are most commonly introduced at the time the
      contrast is drawn up and at the time of contrast injection. The former can be
      reduced by allowing the contrast to stand prior to injection. The latter appears
      to be due to cavitation bubbles and can be reduced by reducing the speed of
      injection. Using current transcranial Doppler machines, it is impossible to be
      certain whether some of the embolic signals, particularly at times other than
      contrast injection, may be due to particulate, rather than air, emboli, but
      technological improvements may allow this distinction to be made in the future.
      (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442967
TI  - Carotid Endarterectomy and Intraoperative Emboli Detection: Correlation of
      Clinical, Transcranial Doppler, and Magnetic Resonance Findings.
AB  - Carotid endarterectomy (CEA) performed with continuous transcranial Doppler (TCD)
      monitoring provides a unique opportunity to determine the number of cerebral
      microemboli and to relate their occurrence to the surgical technique. The purpose
      of this study was to assess in CEA the impact of cerebral microembolism on
      clinical outcome and brain morphology. We also evaluated the influence of the
      audible TCD signal on the surgeon and his/her technique. In a prospective series
      of 301 endarterectomies, brain function was monitored with electroencephalography
      and TCD ultrasonography. Preoperative and intraoperative risk factors were
      entered in a logistic regression analysis program to assess their correlation
      with cerebral outcome. To evaluate the impact of cerebral microembolism on brain
      morphology, we compared preoperative and postoperative magnetic resonance (MR)
      images of the brain in a subgroup of 40 patients. Microemboli (>10) observed
      during the dissection phase of the operation were related to intraoperative (P <
      0.002) and postoperative (P < 0.02) cerebral complications. Microemboli that
      occurred during shunting were also related to intraoperative complications (P <
      0.007). Finally, the phenomenon of >10 microemboli during dissection was
      significantly (P < 0.005) related to new hyperintensive lesions on the
      postoperative T(2)-weighted MR images. The presence of microembolism (>10) during
      the dissection phase of carotid endarterectomy shows a statistically significant
      relationship with perioperative cerebral complications and with new ischemic
      lesions on MR images of the brain. Microembolism during shunting is also related
      to intraoperative complications. Surgeons can be guided by the audio Doppler and
      emboli signals by changing their technique, which may result in a decline of the
      intraoperative stroke rate. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442968
TI  - Doppler Microembolic Signals for Diagnosis of Ulcerated Carotid Artery Plaques.
AB  - BACKGROUND: Finding the pathological meaning of Doppler microembolic signals is
      important to developing the clinical applications of this new technology.
      METHODS: Two hundred eighty-four plaques, removed at carotid endarterectomy, were
      examined by the surgeon and pathologist for evidence of ulceration. The
      ipsilateral middle cerebral artery was monitored, with 2-MHz pulsed Doppler,
      preoperatively and during surgical mobilization of the carotid arteries.
      Associated Doppler embolic signals representing formed element emboli (FEE) were
      sought for 15-273 (mean 60) minutes. The embolization rate was calculated in
      FEE/hour. RESULTS: Preoperatively, 21% of patients demonstrated FEEs. During
      surgical mobilization of the carotid arteries, 51% demonstrated FEEs. A 79%
      prevalence of plaque ulceration was found. Analysis demonstrated 61% sensitivity
      and specificity, and an 86% positive predictive value. The positive predictive
      value increased progressively with higher FEE rates, up to 100% for patients with
      >60 FEE/hour. CONCLUSIONS: FEEs detected in the middle cerebral artery
      ipsilateral to carotid artery stenosis are diagnostic of plaque ulceration or
      luminal thrombus formation. Other embolic sources may be ruled out by monitoring
      the contralateral carotid artery system and the ipsilateral carotid arteries.
      There is no significant relationship between the number and prevalence of FEEs
      and the severity of stenosis or preoperative symptoms. Postoperative cerebral
      complications of stroke were associated with more FEEs than were postoperative
      transient ischemic attacks. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442969
TI  - Emboli and Neuropsychological Outcome Following Cardiopulmonary Bypass.
AB  - The dramatic decline in mortality related to cardiac surgery has resulted in over
      330,000 surgeries involving cardiopulmonary bypass (CPB) being performed yearly
      in the United States. Although few patients die as a result of cardiac surgery,
      over two thirds of the patients demonstrate evidence of acute neuropsychological
      dysfunction postoperatively. The potential mechanisms contributing to post-CPB
      neuropsychological deficits are many, but two major inter-related etiologic
      factors, hypo-perfusion and emboli, are suggested as the probable culprits. If
      embolism is the cause of the deficits, increasing cerebral perfusion would
      deliver more emboli and increase the amount and severity of injury. Conversely,
      if hypoperfusion is the cause of the injury, then decreasing brain blood flow to
      minimize embolic delivery would increase the likelihood of perfusion injury. By
      monitoring the carotid arteries of patients undergoing coronary artery bypass
      graft surgery, we have determined the frequency and quantity of embolic signals
      that occur during CPB. Although we have not been able to determine the nature of
      the embolus, gaseous or solid, we have demonstrated a relationship between the
      overall embolic load and the probability of having NP dysfunction.
      (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442970
TI  - Histologic Studies of Brain Microemboli in Humans and Dogs After Cardiopulmonary
      Bypass.
AB  - Emboli become lodged in the brains of patients undergoing cardiopulmonary bypass
      (CPB) and can cause death, stroke, or more subtle neurological and
      neuropsychological deficits. Using a specialized vascular stain (for alkaline
      phosphatase) in autopsy tissues from the brains of patients who underwent CPB
      shortly before death, we found large numbers of microemboli. All of these
      microemboli contain lipid, some contain small birefringent particles, and some
      may contain aluminum or silicon. Within a few weeks after CPB, most of the
      microemboli had disappeared from the brain tissues, but some persisted for at
      least 6 months. After several days, the endothelial cells of some of the vessels
      containing microemboli showed subtle damage in the form of loss of alkaline
      phosphatase reactivity, and some vessels appeared to be degenerating. Sometimes
      the surrounding neuropil also showed degeneration. Since skin and muscle biopsies
      can be readily obtained before, during, and after CPB, we investigated their
      suitability as surrogate tissues for brain; however, they were unsuitable because
      they had so few microemboli. By injecting microspheres into dogs at various times
      during CPB, we have investigated the timing of the production of microemboli. We
      are also exploring the use of rat brains to trap microemboli from the injected
      blood of patients undergoing CPB. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

PMID- 11442971
TI  - Fundamental Concepts Regarding Sizing and Discrimination of Air Bubbles and Red
      Cell Aggregates Using Pulsed-Doppler Ultrasound.
AB  - The embolus to blood power ratio (EBR) model is briefly described, which predicts
      that emboli become more detectable as Doppler carrier frequency decreases and
      vessel diameter decreases. The EBR model indicates that the use of the
      backscattered power from the blood in the Doppler sample volume and the use of
      more than one carrier frequency will be useful in discriminating size and
      composition of an embolic signal. The EBR model is shown to provide both sizing
      and discrimination of red cell aggregates from air bubbles, using dual frequency
      interrogation of an embolus (1.6 and 2.4 MHz). (ECHOCARDIOGRAPHY, Volume 13,
      September 1996)

PMID- 11442972
TI  - Microembolus Sizing in a Blood-Mimicking Fluid Using a Novel Dual-Frequency
      Pulsed Doppler.
AB  - Sizing of emboli in a blood-mimicking fluid is explored with the application of a
      theoretical description of emboli to embolic signatures obtained in a phantom
      flow loop. The theoretical predictions for the backscattered power versus embolus
      size are based on the embolus to blood power ratio (EBR) model. The experimental
      setup utilizes a customized ultrasound pulsed Doppler that is capable of
      interrogating a sample volume with two different frequencies concurrently.
      Polystyrene "emboli" having nominal diameters of 161 &mgr;m are placed in a
      specially constructed flow loop and scattering signatures are recorded. These
      signatures are investigated and the effect of beam refraction is discussed,
      which, combined with the EBR theory, yields a method to determine embolus size
      from an embolic signal. Embolus size determined experimentally is in close
      agreement with manufacturer's reported size. (ECHOCARDIOGRAPHY, Volume 13,
      September 1996)

PMID- 11442973
TI  - The Contribution of the Left Atrioventricular Plane Displacement During Low Dose
      Dobutamine Stress Echocardiography in Predicting Recovery of Left Ventricular
      Dyssynergies.
AB  - The aim of this study was to assess the significance of the left systolic
      atrioventricular (AV) plane displacement during low dose dobutamine stress
      echocardiography (DSE), in predicting the recovery of left ventricular
      dyssynergies after revascularization. In 30 infarctiers with left ventricular
      dysfunction scheduled for RE (14 percutaneous transluminal coronary angioplasty
      and 16 coronary artery bypass graft) and in 25 age- and sex-matched healthy
      subjects, a DSE, using a 16 ventricular segment model and a four-grade scoring
      system for the assessment of regional wall motion of the left ventricle was
      performed. Prior and during DSE, the left systolic AV plane displacement was
      recorded from the apical four- and two-chamber views, by M-mode echo, at four
      left ventricular sites, corresponding to the septal, lateral, anterior, and
      inferior walls, both in patients and controls. The study was repeated in all
      patients 101 +/- 14 days after successful revascularization. Healthy subjects
      showed a significant increase of left systolic AV plane displacement at all left
      ventricular sites during dobutamine infusion (DI) (P < 0.001). Patients also
      exhibited a significant maximum increase of left systolic AV plane displacement
      during DSE only in the dyssynergic sites with functional improvement in the
      postrevascularization echocardiogram (P < 0.001). In the remaining dyssynergic
      sites, without functional improvement after revascularization, the left systolic
      AV plane displacement did not change (P > 0.05). Selecting a maximum LAVPD
      increase of >2 mm at any site of the left ventricule to predict recovery of the
      regional ventricular dyssynergies, results in a sensitivity of 91%, specificity
      of 83%, positive predictive value of 88%, and negative predictive value of 87%.
      When two-dimensional DSE was used for the detection of reversible dysfunction,
      sensitivity and specificity were found to be 81.5% and 87.5%, respectively, while
      the positive and negative predictive values were 90% and 78%, respectively. When
      the two methods were in agreement the sensitivity was 90%, the specificity 100%,
      and the positive and negative predictive values were 100% and 84.2%,
      respectively. The assessment of left systolic AV plane displacement during DI
      constitutes a new, simple, and accurate method in the prediction of left
      ventricular dyssynergy recovery after revascularization. The combination of this
      method and two-dimensional DSE are basic predictor markers of viability of
      dysfunctional myocardium. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442974
TI  - Validation of Automated Border Detection in Intravascular Ultrasound Images.
AB  - Intravascular ultrasound (IVUS) imaging provides cross-sectional views of the
      vessel lumen; however, lumen measurements still rely on operator-dependent border
      delineation and time-consuming lumen tracings. We tested a new system for
      automated lumen border detection in IVUS images based on acoustic quantification
      of blood and vessel wall. In 10 rabbits, 29 segments of the aorta were imaged in
      vivo using a 2.9-Fr IVUS catheter. IVUS images were obtained during motorized
      pullbacks of aortic segments of 18 mm length. Automated measurements of lumen
      dimensions were compared to automated measurements of a second pullback through
      the same segment, lumen measurements derived from visual border tracings in IVUS
      images, and to quantitative angiography. The automated system showed good
      reproducibility: Correlations for repeated measurements of lumen area, maximal
      and minimal lumen diameters were r = 0.97, r = 0.91, and r = 0.93, respectively.
      Automated measurements also correlated well to visual image analysis (lumen area,
      r = 0.97; maximal lumen diameter, r = 0.89; minimal lumen diameter, r = 0.89) and
      to angiographic measurements (lumen area, r = 0.93; lumen diameter, r = 0.95). In
      12% of the images, the automated system overestimated lumen dimensions because of
      weak wall signals in the presence of echolucent structures next to the wall.
      Signal artifacts from the IVUS catheter itself or strong blood backscatter
      resulted in lumen underestimation in 6% of the images. Over- and underestimation
      of lumen by the border detection system were often associated with eccentric
      catheter position. Thus, lumen measurements in vivo IVUS images can be performed
      using an automated border detection system based on acoustic quantification of
      blood and vessel wall. The system allows reproducible and accurate measurements
      of lumen area and diameters. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442975
TI  - Intravascular Ultrasound Catheter Evaluation of the Left Ventricle in Mice: A
      Feasibility Study.
AB  - With the advent of transgenic technology, it has become increasingly important to
      find a method for evaluating left ventricular (LV) anatomy and function in intact
      wild type, intervened, and transgenic mice. Mice are 1/10th the size of rats, and
      have body masses of 10-60 g, LV masses of 40-150 mg, LV wall thicknesses of 0.5-2
      mm, and LV internal dimensions of 1-3 mm. Although the murine LV has been imaged
      by transthoracic (TTE) two-dimensional directed M-mode echocardiography, we
      explored the use of intravascular ultrasound (IVUS) catheters, with imaging from
      various positions, to see if better two-dimensional images of the LV could be
      obtained by IVUS than TTE. Eight normal mice were anesthetized using
      pentobarbital or avertin. The mice were studied using a commercially available
      IVUS system (Endosonics, Inc.). Two IVUS catheters (3.5 and 5.0 Fr) with 20-MHz
      multielement array transducers were used. Each catheter had a 4.0-mm imaging
      depth of field in all directions (360 degrees ) from the mid-point of the
      catheter core. Multiple imaging approaches were attempted: transesophageal (TEE);
      transjugular (TJ); transperitoneal (TP); and open chest, from both epicardial
      surface (Ep) and via direct LV puncture. TEE and TJ approaches afforded
      insufficient depth of field to image the entire LV in cross section. TP and Ep
      approaches resulted in poor images, related both to inadequate depth of field and
      to relatively small sector angles subtended by imaging elements. LVP
      (intracavitary imaging) was capable of satisfactorily imaging the LV epicardium,
      but was unable to image the endocardium, probably because the latter was within
      the 1.9-mm "ringdown" catheter artifact. All IVUS approach studies lacked
      sufficient temporal resolution (10 frames/sec) to reliably display systolic and
      diastolic frames necessary for evaluation of LV function. In contrast, as
      previously reported, transthoracic two-dimensionally directed M-mode
      echocardiograms have sufficient temporal and spatial resolution to permit
      accurate estimates of LV mass and systolic function. Currently, IVUS catheter
      based approaches are not feasible for imaging murine LV anatomy and function.
      Limitations include: (1) inadequate temporal resolution might be improved by ECG
      gating; (2) limited depth of field possibly resolvable by lower frequency
      transducers; and (3) relatively large catheter size. (ECHOCARDIOGRAPHY, Volume
      13, November 1996)

PMID- 11442976
TI  - Three-Dimensional Echocardiographic Reconstruction of the Left Ventricle by a
      Transesophageal Tomographic Technique: In Vitro and In Vivo Validation of its
      Volume Measurement.
AB  - Accurate determination of left ventricular (LV) volume has important therapeutic
      and prognostic implications in patients with cardiac disease. Volume estimations
      by two-dimensional techniques are not very accurate due to geometric assumptions.
      OBJECTIVES: To validate LV volume determinations by a new transesophageal three
      dimensional echocardiographic technique. We performed three-dimensional
      reconstruction of the LV using an echo-computed tomographic (CT) technique based
      on serial pullback parallel slice imaging technique in both in vitro and in vivo
      settings. Fourteen latex balloons with various sizes (30-235 mL) and shapes
      (conical, pear shaped, round, elliptical, and aneurysms in various locations)
      filled with known volumes of water were imaged in a water bath. From the static
      three-dimensional image, the LV long axis was defined and the LV was sectioned
      perpendicular to this axis into 2-mm slices. The volume of each slice was
      calculated with the observer blinded to the actual volume as the product of the
      slice thickness and the manually traced perimeter of the slice and the LV volume
      as the sum of the volumes of the slices (Simpson's method). The calculated LV
      volume closely correlated with the actual volume (r = 0.99, P < 0.0001,
      calculated volume = 1.06x - 11.3, Deltavolume = -5.7 +/- 10.0 cc). Using the same
      system, transesophageal echocardiographic (TEE) images of the LV were obtained in
      15 patients gated to respiration and ECG. Satisfactory dynamic three-dimensional
      reconstruction of the LV was possible in ten patients. The three-dimensional LV
      volumes (systolic and diastolic) using Simpson's method correlated well with
      those obtained from biplane or multiplane TEE images using the area length method
      (r = 0.89, p < 0.0001, y = 12.7 + 0.84x, Deltavolume = 1.3 +/- 18.1 cc). The LV
      major-axis diameters by the two methods showed very close correlations as well (r
      = 0.86, P < 0.0001, y = 19 + 0.74x, Deltadiameter = 1.0 +/- 7.2 mm). We conclude
      that three-dimensional LV volume calculation by the echo-CT technique is
      intrinsically sound, is independent of LV geometry, and with some limitations, is
      applicable in vivo. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442977
TI  - A Case of Cardiac Amyloidosis Presenting with Mid- to Late Diastolic Retrograde
      Flow from the Left Atrium to the Pulmonary Vein: Transesophageal Pulsed Doppler
      Echocardiographic Observations.
AB  - A patient of cardiac amyloidosis was found to have mid- to late diastolic
      retrograde flow from the left atrium (LA) to the pulmonary vein. Congo-red
      staining was positive for amyloid in the rectal tissue. M-mode and two
      dimensional echocardiograms revealed symmetric hypertrophy and typical speckled
      pattern of the left ventricle (LV). The LV pressure curve showed a dip and
      plateau configuration during diastole, and end-diastolic pressure was 28 mmHg. In
      addition, the LV pressure was high at mid-diastole, surpassing the pulmonary
      capillary wedge pressure from mid- to late diastole. The transmitral flow
      velocity revealed "restrictive" pattern, and the pulmonary venous flow velocity
      showed retrograde flow from the LA to the pulmonary vein during mid-diastole and
      atrial systole. It is suggested that recording of the pulmonary venous flow
      velocity by transesophageal pulsed Doppler echocardiography is useful for
      understanding the mechanism of the development of pulmonary congestion or edema.
      (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442978
TI  - Mediastinal Tumor Presenting as Expanding Aortic Aneurysm Diagnosed by
      Transesophageal Echocardiography.
AB  - This article describes a patient with suspected expanding ascending aortic
      aneurysm in whom transesophageal echocardiography appropriately determined the
      presence of a mediastinal soft tissue mass and visualized compression of the
      superior vena cava. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442979
TI  - Color Doppler Transesophageal Echocardiography in Detection of Massive Pulmonary
      Embolism: Is Pulmonary Angiography Always the Gold Standard?
AB  - In this article, the potential value of color Doppler in improving diagnostic
      accuracy of transesophageal echocardiography (TEE) in patients with incomplete
      obstruction of large pulmonary vessels is illustrated. We present an unusual case
      of massive pulmonary embolism that was unequivocally detected by color Doppler
      TEE both before and after pulmonary angiography, which failed to demonstrate
      filling defects in the pulmonary artery. (ECHOCARDIOGRAPHY, Volume 13, November
      1996)

PMID- 11442980
TI  - Mitral Stenosis, Sinus Venosus Atrial Septal Defect, and Partial Anomalous
      Pulmonary Venous Return: Diagnosis by Multiplane Transesophageal
      Echocardiography.
AB  - We describe a 42-year-old man with rheumatic mitral stenosis, sinus venosus
      atrial septal defect, and anomalous drainage of the right upper pulmonary vein to
      the superior vena cava. Transthoracic echocardiography (TTE) failed to identify
      the atrial septal defect and the partial anomalous pulmonary venous return.
      Transesophageal echocardiography (TEE), using a multiplane probe, was useful in
      delineating the abnormalities. To our knowledge, this is the first reported
      patient with rheumatic mitral stenosis and sinus venosus defect.
      (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442981
TI  - Acquired Intercostal Arteriovenous Fistulas: Transesophageal Doppler
      Echocardiographic Diagnosis.
AB  - Acquired intercostal arteriovenous fistulas are recognized complications of
      traumatic injuries. In this article, transesophageal Doppler echocardiographic
      findings in a patient with posttraumatic acquired intercostal arteriovenous
      fistulas are presented. The findings have been confirmed by angiography. The
      demonstration of intercostal arteriovenous fistulas by transesophageal Doppler
      echocardiography has not been reported before. (ECHOCARDIOGRAPHY, Volume 13,
      November 1996)

PMID- 11442982
TI  - Postmyocardial Infarction Intramyocardial Hematoma and Rupture.

PMID- 11442983
TI  - Color Doppler Visualization of Intramyocardial Coronary Arteries Using a New Echo
      System: Effect of Contrast Enhancement and Vasodilation.
AB  - Utilizing a new echocardiographic system, intramyocardial coronary arteries could
      be demonstrated by color Doppler in a small number of open chest animals. Both
      intravenous and intracoronary injections of a contrast agent (Levovist) resulted
      in significant enhancement of color flow signals with an increase in the length,
      width, and the number of these vessels. Similar results were obtained with
      intravenous infusion and direct intracoronary injections of a vasodilator
      (adenosine). (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442984
TI  - Multiplane Transesophageal Echocardiography for Congenital Heart Disease:
      Leveling the Playing Field.

PMID- 11442985
TI  - The Usefulness of Transesophageal Echocardiography in the Surgical Management of
      Older Children with Subaortic Stenosis.
AB  - Subaortic stenosis is a complex lesion that often presents in older children and
      adolescents. A clear depiction of the lesion is required for optimization of
      surgery. Due to the large size of these patients, is not always possible from
      surface echocardiography. Intraoperative multiplane echocardiography (MTEE) has
      been performed at our institute in older children for several different
      congenital heart lesions including many patients with subaortic stenosis. A
      retrospective analysis of our experience with MTEE in patients with subaortic
      stenosis was performed to assess its usefulness in the preoperative diagnosis and
      postoperative assessment of repair. Our results show that intraoperative MTEE was
      useful preoperatively by correcting or confirming suspected diagnosis, and giving
      additional details of the lesion in many patients. Postoperatively, MTEE was
      highly useful in the assessment of repair. We strongly recommend the use of
      intraoperative MTEE in older children and adolescents with subaortic stenosis.
      (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442986
TI  - Multiplane Transesophageal Echocardiographic Evaluation of Defects of the
      Atrioventricular Septum: The Crux of the Matter.
AB  - The availability of multiplane transesophageal probes has dramatically
      facilitated visualization of complex cardiac anatomy, with full dynamic tracking
      of anatomic contiguity. This report describes the unique applicability of
      multiplane transesophageal echocardiography (TEE) for visualization and
      assessment of a spectrum of congenital cardiac defects involving the cardiac
      crux, including the atrioventricular septum, inlet muscular septum, and the
      atrioventricular valves. With further evolution and progressive miniaturization
      of these probes, the use of this echocardiographic modality will hopefully
      encroach into the young infant age range, permitting enhanced preoperative and
      perioperative depiction of complex congenital cardiac anatomy. (ECHOCARDIOGRAPHY,
      Volume 13, November 1996)

PMID- 11442987
TI  - 7.5-MHz Pediatric Phased Array Transesophageal Endoscope.
AB  - This work extends the clinical benefits of phased array transesophageal
      echocardiography with high detail and contrast resolution to include neonatal
      patients. We have built several prototype, 64-element, 7.5-MHz phased array
      transducers housed in 6.2-mm endoscope shafts for use with commercially available
      imaging systems. The acoustic design is standard, but the miniaturized packaging
      of the electrical connections was quite challenging. The endoscopes demonstrate
      very good structural resolution and excellent sensitivity for color flow imaging
      and continuous-wave Doppler. They have been used on patients as small as 1.9 kg,
      frequently as an anatomical guide during catheter-based interventions and during
      congenital heart surgery. Array test data and representative clinical studies are
      shown. (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442988
TI  - Pediatric Transesophageal Echocardiography by Means of a Miniature 5-MHz
      Multiplane Transducer.
AB  - The development of a miniature multiplane transesophageal echocardiographic (TEE)
      transducer for pediatric use is the latest development in TEE. Horizontal,
      longitudinal, and all possible intermediate oblique planes can be obtained with
      minimal transducer manipulation. We studied 48 patients with an experimental 5
      MHz transducer, which contains 48 transmitting elements. The dimensions of the
      tip are 27 x 10.6 x 7.9 mm. Patients ages ranged from 2 days to 16 years, their
      weights from 3.6-67 kg. Multiplane TEE proved to be complementary to the single
      horizontal plane in assessing the right ventricular outflow tract, the left
      ventricular outflow tract, ascending aorta, the atrial septum, the
      atrioventricular (AV) valves, especially in AV septal defects, and double inlet
      left ventricle (DILV). Moreover, multiplane TEE was extremely helpful in judging
      the outflow tracts and ventricular septal defects in more complex heart defects
      such as DILV, double outlet right ventricle, and hearts with discordant
      connections. Multiplane TEE offered superb monitoring of cardiac interventions.
      We conclude that multiplane TEE provides new imaging planes and enables
      visualization of every major structure of the heart by unlimited scan planes.
      Multiplane TEE is indispensable in congenital heart defects. Thus, multiplane TEE
      adds to diagnostic assurance and enhances decision making for surgery.
      (ECHOCARDIOGRAPHY, Volume 13, November 1996)

PMID- 11442990
TI  - Antimicrobial resistance trends in common urinary pathogens.
AB  - Urinary tract infections (UTIs) are the second most common infectious
      presentations in community practice. Over 90% of UTIs are due to a single
      species. Escherichia coli alone accounts for 80% to 90% of UTIs. In young,
      healthy women, Staphylococcus saprophyticus accounts for approximately 5% to 15%
      of cases of uncomplicated cystitis, but is rarely associated with pyelonephritis
      or complicated infections. Other gram-negative species comprise the majority of
      the remaining causes of UTIs. Because initial antimicrobial therapy for UTIs is
      generally empiric, it is important to account for local susceptibility trends
      when selecting an antimicrobial agent. In Canada, resistance among community
      acquired (as opposed to nosocomial or hospital-acquired) isolates of E. coli
      varies depending on the antimicrobial agent being tested. Ampicillin has the
      lowest activity against community-acquired E.coli isolates, with resistance rates
      ranging from 23% to 41%. Trimethoprim-sulphamethoxazole (TMP-SMX) resistance
      rates range from 8.4% to 19.2%, while the resistance to the fluoroquinolone
      ciprofloxacin has remained at 0% to 1.8% since its introduction over 10 years
      ago. Current studies suggest that there are no regional differences in resistance
      rates among community-acquired urinary tract pathogens across Canada.

PMID- 11442991
TI  - Urinary tract infections in women.
AB  - Urinary tract infections (UTIs) are the most common infections seen in the
      hospital setting, and the second most common infections seen in the general
      population. Due to women's anatomy, UTIs are especially problematic for them, and
      up to one-third of all women will experience a UTI at some point during their
      lifetimes. Appropriate treatment of a UTI requires accurate classification that
      includes infection site, complexity of the infection, and the likelihood of
      recurrence. The predominant pathogen in both complicated and uncomplicated UTI
      remains pathogenic Escherichia coli, although Klebsiella sp. and Proteus appear
      with increased frequency in complicated UTI. Most often, bacteria cause UTIs by
      ascending means through the urethra into the bladder. Bacteria must possess
      virulence factors to cause UTI. Host defense factors that predispose patients to
      UTI include urinary stasis, abnormal urinary tract anatomy, diabetes mellitus,
      debility, and aging. Estrogen-related issues and short urethras predispose women
      to UTI. Although urine culture, with >105 colony-forming units/mL (CFU/mL) in
      symptomatic patients, remains the diagnostic "gold standard," correlation of the
      patient's history and physical examination with urinalysis (including nitrite
      dipstick and leukocyte esterase test) results usually suffices to diagnose UTI.
      Three-day of antimicrobial treatment is recommended for simple cystitis. Acute
      pyelonephritis, an infection of the kidney parenchyma tissue, is treated with
      antibiotics for 7 to 14 days depending on the antimicrobial agent used and the
      severity of infection. In addition, patient classification determines the need
      for hospitalization or for urological imaging studies. Women with recurrent UTIs
      merit consideration for antimicrobial prophylaxis. Self-administered topical
      vaginal estradiol cream is an important adjunct in UTI prevention for
      postmenopausal women. Asymptomatic bacteruria only merits antimicrobial therapy
      in high-risk patients or those colonized with Proteus species.

PMID- 11442992
TI  - Complicated urinary tract infections in patients with voiding dysfunction.
AB  - Complicated urinary tract infections (UTIs) occur in patients who have
      structurally or functionally abnormal urinary tracts -- in contrast to simple
      cystitis, which usually occurs in young, healthy females who have normal anatomy.
      Because of their abnormal anatomy, patients with complicated UTIs can be
      exceedingly difficult to treat. Successful treatment usually requires correction
      of the underlying anatomical problem, but this may not possible, so relapse of
      the infection is the general rule. Although most infections are still caused by
      Escherichia coli, many are caused by more exotic and highly resistant coliforms,
      such as citrobacter and pseudomonas. As well, gram-positive bacteria such as
      staphylococcus and enterococcus can be found. In patients with spinal cord
      injuries, high bladder pressure due to obstruction at the sphincter level can
      cause obstruction and/or reflux. In these patients, as well as in patients with
      benign prostatic hypertrophy, and in geriatric women, high residual bacteria
      levels prevent washout of bacteria. Other possibly significant risk factors
      include poor fluid intake, poor hygiene, and poor nutrition that results in
      decreased immunity. Finally, the unavoidable use of catheters actively introduces
      bacteria into the urinary tracts of these patients. Prevention by modifying as
      many of these risk factors as possible is essential to reduce attack rates of
      UTIs. Treatment must be guided by the results of urine cultures. Broad-spectrum
      coverage including anti-pseudomonal activity is preferable, and the
      fluoroquinolones, eg. ciprofloxacin or levofloxacin, seem to fit this bill
      perfectly. If possible, physicians should start by prescribing oral antibiotics
      for a minimum of 10 days and maybe for a lot longer, as indicated. There is no
      role for short-course therapy. Other options include oral, second-generation
      cephalosporins, or intravenous therapy with aminoglycosides and piperacillin.
      Physicians must be prepared to treat aggressively for prolonged periods.
      Unfortunately, reinvestigation, reculturing, and retreatment are usually
      required.

PMID- 11442993
TI  - Pediatric urinary tract infections: current controversies.
AB  - Few topics in pediatric urology engender such vigorous debate as the who, when,
      how, and why related to the investigation of pediatric urinary tract infections
      (UTIs). Further controversy stems from management of the underlying pathology.
      This article first discusses the patient characteristics that are important in
      the evaluation of pediatric patients with UTIs, and the indications for screening
      tests (such as voiding cystourethrograms, ultrasound, dimercaptosuccinic acid
      renal scintigraphy, and intravenous pyelography). Following this, the author
      reviews what is known about three controversial aspects about the management of
      these patients. First, although the role of the prepuce in pediatric UTI is well
      established, the role of routine circumcision is not. Second, the natural history
      and etiology of antenatally detected vesicoureteral reflux (VUR) has provoked us
      to view the concept of "primary reflux" in a new light. Third, although the way
      to diagnose vesicoureteral reflux is generally agreed upon, the utility of our
      surgical management in view of long-term follow-up is less clear.

PMID- 11442994
TI  - Use of antibiotics in chronic prostatitis syndromes.
AB  - Chronic prostatitis is a common condition, with an incidence estimated at between
      9%-14% of men worldwide. It is a medically controversial condition with
      significant attendant morbidity. According to a recent consensus report from the
      National Institutes of Health (NIH), chronic prostatitis patients fall into one
      of three categories: chronic bacterial prostatitis (category II prostatitis);
      chronic pelvic pain syndrome (category III prostatitis); or asymptomatic
      inflammation (category IV prostatitis). Prostatic tissues are best penetrated by
      drugs with a high pKa and high lipid solubility, such as quinolones, macrolides,
      tetracyclines, and sulfa drugs. Ciprofloxacin has been shown to be effective in
      the treatment of chronic bacterial prostatitis caused by Escherichia coli. The
      older quinolones demonstrate superiority against chronic bacterial prostatitis
      caused by gram-negative pathogens; the newer quinolones may be more effective
      against gram-positive pathogens and anaerobes. Despite continuing controversy,
      antimicrobial agents are the most common therapy employed in the treatment of
      chronic prostatitis. While some patients with nonbacterial (category III)
      prostatitis do improve with antibiotics, prolonged courses in the absence of
      documented infection or symptomatic improvement are not warranted. Prospective,
      randomized, placebo-controlled trials will hopefully lead to a clearer
      understanding of the role of antimicrobial agents in chronic bacterial
      prostatitis within the next year.

PMID- 11442995
TI  - The management of acute pyelonephritis in adults.
AB  - Acute pyelonephritis should be classified clinically at the time of presentation
      into either uncomplicated or complicated categories. The diagnostic workup
      includes history, physical examination, urinalysis (including a Gram stain), and
      urine culture. Patients with suspected complicated pyelonephritis require the
      standard assessment plus blood cultures and urinary tract imaging, preferably a
      computed tomography (CT) scan. Patients with moderate, uncomplicated
      pyelonephritis can be managed as outpatients with either a fluoroquinolone (7-14
      days) or trimethoprim/sulfamethoxazole (at least 14 days). Patients with severe,
      uncomplicated pyelonephritis can be considered for short-term hospitalization and
      initial administration of intravenous antibiotics. Therapy for patients with
      complicated pyelonephritis should include initial hospitalization, supportive
      therapies, administration of wide spectrum intravenous antibiotic therapy, and
      relief of aggravating conditions. Such maneuvers could consist of simple bladder
      catheterization, percutaneous nephrostomy drainage, or definitive surgery.
      Patients with complicated pyelonephritis require longer duration of culture
      specific antibiotic dosing, careful monitoring, long-term follow-up, and possible
      definitive management of their underlying condition.

PMID- 11442996
TI  - Hypoxia regulation of gene transcription.
AB  - The adaptive responses to hypoxia include the transcriptional activation of
      various genes like those encoding for glycolytic enzymes, growth factors and
      vasoactive peptides that tend to ameliorate the damaging effect of the lack of
      oxygen. Most of these genes are regulated by the hypoxia-inducible factor 1
      complex (HIF-1), a heterodimer protein complex that activates transcription
      through binding to specific hypoxic-responsive sequences (HRE) present in those
      genes. Hypoxia induces HIF-1 complex formation by stabilizing the HIF-1alpha sub
      unit, which under normoxic conditions is degraded by the ubiquitin-proteasome
      system. The molecular mechanisms by which cells sense the hypoxic signal and
      transduce the hypoxic response are still not clear. The more accepted models for
      oxygen sensing involve the participation of heme-proteins sensors or are based in
      redox-reactions which may or not involve participation of mitochondria.

PMID- 11442997
TI  - Hypoxia-dependent protein expression: erythropoietin.
AB  - Normal cell homeostasis relies on the ordered flow of nutrients and substrates
      through metabolic pathways. Any perturbation of this flow eventually leads to
      dysfunction, impairment of defense mechanisms, loss of viability and death. High
      altitude and pathological hypoxia represent a serious and frequent cause for the
      loss of cell viability. Although organisms customarily respond by triggering
      adaptive or maladaptive mechanisms, all forms of life eventually succumb to
      hypoxia if it is severe enough, irrespectively of the primary cause. This paper
      reviews one of the mechanisms by which organisms respond to hypoxia:
      erythropoiesis. Although such response is not always beneficial, the discovery of
      the biochemical mechanisms underlying erythropoiesis has triggered an active
      field of research that is actually applying lessons learned in the mountains to a
      more clinical environment.

PMID- 11442998
TI  - Potential genetic contributions to control of the pulmonary circulation and
      ventilation at high altitude.
AB  - This review examines evidence that genetic factors may be important determinants
      of response of the pulmonary circulation and ventilation at high altitude. Early
      observations of cattle at high altitude with brisket disease-pulmonary
      hypertension with right heart failure-found that the disorder ran in families.
      Subsequent studies confirmed a genetic determination of the pulmonary
      vasoconstrictor response to hypoxia by selective breeding of cattle for high and
      low responses. Clear interspecies and interstrain differences in the hypoxic
      pulmonary pressor response also underscore a major role for genetic influence in
      animals. In humans, differences in pulmonary hemodynamics are also evident among
      discrete populations living at altitude in the Andes, Himalayas, and North
      America suggesting an evolutionary, genetic influence on the response of the lung
      circulation to the hypoxia of altitude. Ventilation is increased by the hypoxia
      of high altitude. The strength of the ventilatory response to hypoxia shows
      considerable variation among individuals at low altitude. Family clusters of high
      and low responses and greater concordance among identical than fraternal twins
      suggest a strong genetic modulation of the human hypoxic ventilatory response.
      Similar effects are seen in interstrain differences among inbred strains of rats
      and mice. Differences among diverse altitude populations support the possible
      influence of genetic variation in the hypoxic response on ventilation and
      adaptation at altitude. Mechanisms linking genetic influences to variation in the
      hypoxic pulmonary pressor and ventilatory responses are unknown, but could
      reflect effects on hypoxic sensor, mediator or effector limbs of the response.

PMID- 11442999
TI  - Role of vascular smooth muscle in the development of high altitude pulmonary
      hypertension: an interspecies evaluation.
AB  - There is a marked variability in the degree of pulmonary hypertension induced by
      long-term exposure to altitudes above 3000 m among low altitude species, ranging
      from hyporesponders (sheep and dogs) to hyper-responders (cattle and pigs). The
      amount of inherent muscularization of small pulmonary arteries appears to be a
      determinant of this hypertensive response, as does the presence or absence of
      collateral ventilation. Hyper-responders also exhibit marked pulmonary vascular
      hypertrophy when exposed to long-term hypoxia. Humans exhibit similar inter- and
      intra-population variability. Animal species indigenous to high altitudes exhibit
      less variable, attenuated pulmonary hypertensive responses with little pulmonary
      vascular hypertrophy. This attenuated response is also apparent among human high
      altitude populations, particularly in Andean and Tibetan populations. Thus,
      successful adaptation to high altitudes is evident in species that do not sustain
      the acute cardiopulmonary compensations that occur upon initial exposure to high
      altitude.

PMID- 11443000
TI  - Challenges implicit to gene discovery research in the control of ventilation
      during hypoxia.
AB  - Appointing physiological function to specific genetic determinants requires a
      systems physiologist to consider ways of assessing precise phenotypic mechanisms.
      The integration of ventilation, metabolism and thermoregulation, for example, is
      very complex and may differ among small and large mammalian species. This
      challenge is particularly applicable to the study of short- and long-term
      adaptation of these systems to hypoxic exposure associated with high altitude.
      Our laboratory has initiated a research effort to dissect the complexity of
      hypoxic adaptation using traditional quantitative genetic analysis and
      contemporary DNA genotyping techniques. Although the current evidence in murine
      models demonstrates that specific genes influence control of hypoxic ventilatory
      responses (HVR), the relevance of these determinants to human adaptation to
      altitude remains open to exploration. Our review discusses the progress and
      uncertainties associated with assigning a genetic basis to variation in acute and
      chronic HVR.

PMID- 11443001
TI  - Angiotensin-converting enzyme and genetics at high altitude.
AB  - As part of the renin-angiotensin system (RAS), angiotensin-converting enzyme
      (ACE) plays a key role in circulatory homeostasis. ACE degrades vasodilator
      kinins and generates angiotensin II. A polymorphism in intron 16 of the human ACE
      gene has been identified in which the presence (insertion, I allele) rather than
      the absence (deletion, D allele) of a 287 bp fragment is associated with lower
      serum and tissue ACE activity. The I allele has been associated with some aspects
      of endurance performance, being found with excess frequency in elite distance
      runners, rowers, and other elite athletes. Mountaineers also demonstrate an
      allele skew with a significant excess of the I allele and II genotype in elite,
      male, British mountaineers who have ascended beyond 7000 m without the use of
      supplemental oxygen. This review evaluates the evidence for and against an
      association of the I allele with human endurance, and performance at high
      altitude. We conclude that the I allele does confer an advantage, most likely
      mediated via improved muscle efficiency with secondary benefits in terms of
      conservation of non-fat mass.

PMID- 11443002
TI  - Limits on inferring genetic adaptation to high altitude in Himalayan and Andean
      populations.
AB  - Many physiological and anthropological studies have investigated the unique
      Andean and Himalayan populations that have resided for many hundreds of
      generations at high altitude (HA). A nonscientific survey of the extant
      literature reveals a relatively liberal tradition of inferring genetic
      (evolutionary) adaptation to HA in these groups, often based on limited evidence
      and/or based on study designs insufficient to fully address the issue. In order
      to provide some perspective, I review relevant methodological issues that should
      be considered before evolutionary inference is made. On the whole, this paper
      takes a conservative stance and cautions against evolutionary inference based on
      the serious limitations of currently applied research approaches.

PMID- 11443003
TI  - Origin and evolutionary relationships of native Andean populations.
AB  - This paper represents an effort to explore the origin and the evolutionary
      relationships of native Andean populations using a multidisciplinary approach.
      Archeological and linguistic evidence is briefly reviewed. A genetic distance
      analysis among major linguistic groupings and among Andean and Amazonian native
      populations, together with information obtained from archaeological and
      linguistic sources was used to generate a migration model. It is suggested that
      in the late Pleistocene a group of nomadic hunters entered South America through
      the Isthmus of Panama and split afterwards into two groups, one moving southward
      into the central and south Andean areas and after crossing the Colombian, Equador
      and Peruvian highlands to people northwestern Argentina, the open park country of
      east Brazil and the Argentine Pampas. The second group migrated eastwards into
      Venezuela and Guyana and later southward, peopling the Brazilian Amazon.
      Following available waterways the Amazonian Indians expanded east and west
      arriving probably at the eastern slopes of the Andes some 3,500 years ago. It is
      hypothesized that present day Andean natives are descendants of the Amazonian
      groups that migrated eastwards.

PMID- 11443004
TI  - The evidence for hereditary factors contributing to high altitude adaptation in
      Andean natives: a review.
AB  - Humans have occupied the high plateaus and mountain valleys of the Andes and the
      Himalayas for thousands of years. Although sea level natives can, and often do,
      travel in these rarefied reaches, there is little doubt that natives born and
      raised in the "thin" air are better equipped to deal with the reduced
      availability of oxygen at altitude. What fraction of the hypoxia defense response
      of high altitude native populations is due to developmental adaptations acquired
      during growth and what fraction is due to a genetic component reflecting the
      effects of selective transmission of beneficial genetic variants through hundreds
      of generations of antecedents is as yet unresolved. This paper summarizes some of
      the studies that have been undertaken to address this issue in Andean indigenous
      populations, primarily with respect to those adaptations thought to be involved
      in the uptake, distribution and utilization of oxygen in children and adults.
      Specifically, it focuses on changes in chest morphology, pulmonary function,
      metabolism and hematology. Space constraints preclude extending this review to
      the large body of literature concerning prenatal and maternal adaptations
      although this critical stage in development has likely been subject to
      significant selective pressures. It is apparent that both nature and nurture
      influence the acquisition of a high altitude phenotype in humans and while there
      is some evidence for genetic adaptation in Andean highlanders, it is evident that
      these characteristics are expressed in concert with substantial environment
      dependent developmental adjustments.

PMID- 11443005
TI  - Human genetic adaptation to high altitude.
AB  - Some 140 million persons live permanently at high altitudes (>2500 m) in North,
      Central and South America, East Africa, and Asia. Reviewed here are recent
      studies which address the question as to whether genetic adaptation to high
      altitude has occurred. Common to these studies are the use of the oxygen
      transport system and the passage of time as organizing principles, and the
      recognition of the multifaceted ways in which genetic factors can influence
      physiological processes. They differ in terms of study approach and sources of
      evidence for judging duration of high altitude residence. Migrant, family set,
      and admixture study designs have been used for comparisons within populations.
      These collectively demonstrate the existence of genetic influences on
      physiological characteristics of oxygen transport. Differences in oxygen
      transport-related traits between Tibetan, Andean and European populations have
      been interpreted as having demonstrated the existence of genetic influences on
      high altitude adaptation but there is not consensus as to which groups are the
      best-adapted. Part of the controversy lies in the kinds of evidence used to
      assess duration of high altitude habitation. More other information is needed for
      a fuller appreciation of duration of residence and also features of population
      history (genetic drift, gene flow) but existing data are consistent with Tibetans
      having lived at high altitude longer than the other groups studied. Another issue
      surrounds usage of the term "adaptation." The definition should be based on
      evolutionary biology and physiological traits linked to indices of differential
      fertility and/or mortality. Two examples are developed to illustrate such
      linkages; intrauterine growth restriction (IUGR) at high altitude and the
      prevalence of Chronic Mountain Sickness (CMS). Interpopulational as well as
      intrapopulational variation exists in these conditions which appear linked to
      characteristics of oxygen transport. Both adversely influence survival and appear
      to be less severe (IUGR) or less common (CMS) among Tibetans than other groups.
      Thus available evidence suggest that Tibetans are better adapted. Needed,
      however, are studies which are better controlled for population ancestry,
      especially in South America, to determine the extent to which Tibetans differ
      from Andean highlanders. More precise information is also needed regarding the
      genetic factors underlying characteristics of oxygen transport. Such studies in
      Tibetan, Andean and Europeans as well as other high altitude populations offers a
      promising avenue for clarifying the adaptive value of physiological components of
      oxygen transport and the extent to which such factors differ among high altitude
      populations.

PMID- 11443008
TI  - Assessment of high altitude tolerance in healthy individuals.
AB  - The most reliable prediction of high altitude tolerance can be derived from the
      clinical history of previous comparable exposures. Unfortunately, there are no
      reliable tests for prediction prior to first-time ascents. Although
      susceptibility to AMS is usually associated with a low hypoxic ventilatory
      response (HVR), there is too much overlap with the range of normal values, which
      precludes measuring HVR or O(2) saturation during brief hypoxia for reliable
      identification of susceptibility to AMS. A low HVR and an exaggerated rise in
      pulmonary artery pressure with (prolonged) hypoxia, or exercise in normoxia, are
      markers of susceptibility to high altitude pulmonary edema (HAPE). These tests
      can not be recommended for routinely determining high altitude tolerance because
      the prevalence of susceptibility to HAPE is low and because specificity and
      sensitivity of these tests are not sufficiently established. On the other hand,
      HAPE may be avoided in susceptible individuals by ascent rates of 300 m per day
      above an altitude of 2000 m. Since prediction of risk of mountain sickness is
      difficult, it is important during the physician consultation prior to ascent to
      consider the altitude profile, the type of ascent, the performance capacity, the
      history of previous exposures, and the medical infrastructure of the area.

PMID- 11443009
TI  - Highlights of the Congress on Hypothermia and Cold Injuries: Brunico (Bruneck),
      Italy; September 21-24, 2000.

PMID- 11443010
TI  - Isolated facial and hypoglossal nerve palsies at high altitude.
AB  - A variety of neurological disorders other than high altitude cerebral edema have
      been described at high altitude. This report documents isolated facial and
      hypoglossal nerve palsies that occurred in two travellers at high altitude in the
      Nepal Himalaya. The possible pathophysiological mechanisms of these neurological
      deficits are discussed.

PMID- 11443011
TI  - Mountain medicine citations.

PMID- 11443013
TI  - The Silver Hut expedition.

PMID- 11443014
TI  - The burden of the Himalayan porter.

PMID- 11443016
TI  - Telemedicine and the older patient.

PMID- 11443017
TI  - My place or yours--what is the best place for early stroke care?

PMID- 11443018
TI  - Distal forearm fracture--time for action?

PMID- 11443019
TI  - Teleconsultation in psychology: the use of videolinks for interviewing and
      assessing elderly patients.
AB  - Although elderly people are one of the major target groups for telemedicine
      applications, they remain under-represented in studies of teleconsultation.
      Videolinks appear to be easily used by many elderly people as a means of
      communicating with health-care staff, including psychologists and doctors. To
      date, studies of psychometric teleconsultation have been confined to screening
      tests, or have used very small numbers of patients. There is a need to examine
      the reliability of more complex psychometric batteries and to use larger samples
      of older people. Some recommendations for conducting clinical interviews and
      psychometric tests are presented, based on clinical experience and a review of
      the literature. The importance of ergonomic considerations, patient comfort and
      professional preparation are explained.

PMID- 11443020
TI  - Does admission to hospital improve the outcome for stroke patients?
AB  - OBJECTIVES: to identify the factors associated with hospital admission and the
      differences in management and outcome of stroke patients between hospital and
      home. DESIGN: a prospective community stroke register (1995-8) with multiple
      notification sources. SETTING: an inner city multi-ethnic population of 234 533
      in South London, UK. PARTICIPANTS: 975 subjects with first in a lifetime strokes,
      whether or not they were admitted to hospital. Patients dying suddenly and those
      already hospitalized at the time of stroke were excluded. MAIN OUTCOME MEASURES:
      factors associated with hospital admission; differences in management in the
      acute phase of stroke; mortality and dependency assessed by the Barthel index 3
      months post-stroke. RESULTS: 812 patients were admitted to hospital for stroke;
      163 were managed in the community. Factors independently associated with hospital
      admission included stroke severity, pre-stroke independence, atrial fibrillation,
      having an intracranial haemorrhage and having a non-lacunar infarction. Computed
      tomography scan rates were higher in admitted (78%) than non-admitted patients
      (63%; P=0.001). By 3 months, 285 (35%) of the admitted patients had died compared
      with 13 (8%) of non-admitted patients (P<0.001). Of the admitted patients, 241
      (47%) had a Barthel index > or =18 compared with 106 (72%) of those who were not
      admitted (P<0.001). After adjusting for case-mix variables, the odds ratios for
      death and dependency (Barthel index<18) in admitted and non-admitted patients
      were 2.21 (0.96-5.12) and 2.39 (1.35-4.22) respectively. CONCLUSION: patients
      with clinical indicators for a more severe stroke were more likely to be admitted
      to hospital. Hospitalized stroke patients may have poorer survival and disability
      rates than those who remain at home, even after adjustment for case mix. There
      may be some aspects of acute hospital care that may be detrimental to outcome in
      certain groups of stroke patients. This requires further investigation.

PMID- 11443021
TI  - Pharmacist-led medication review in patients over 65: a randomized, controlled
      trial in primary care.
AB  - BACKGROUND: regular medication review has been recommended for those over 75 and
      those on multiple drug therapy. Pharmacists are a potential source of assistance
      in reviewing medication. Evidence of the benefits of this process is needed.
      OBJECTIVE: to study the effect of medication review led by a pharmacist on
      resolution of pharmaceutical care issues, medicine costs, use of health and
      social services and health-related quality of life. DESIGN: randomized,
      controlled trial. SETTING: general medical practices in the Grampian region of
      Scotland. SUBJECTS: patients aged at least 65 years, with at least two chronic
      disease states who were taking at least four prescribed medicines regularly.
      METHODS: pharmacists reviewed the drug therapy of 332 patients, using information
      obtained from the practice computer, medical records and patient interviews. In
      168 patients, a pharmaceutical care plan was then drawn up and implemented. The
      164 control patients continued to receive normal care. All outcome measures were
      assessed at baseline and after 3 months. RESULTS: all patients had at least two
      pharmaceutical care issues at baseline. Half of these were identified from the
      prescription record, the rest from notes and patient interview. Of all the
      issues, 21% were resolved by information found in notes and 8.5% by patient
      interview. General practitioners agreed with 96% of all care issues documented on
      the care plans in the intervention group. At the time of follow-up, 70% of the
      remaining care issues had been resolved in the intervention group, while only 14%
      had been resolved in the control group. There were no changes in medicine costs
      or health-related quality of life in either group. There were small increases in
      contacts with health-care professionals and slightly fewer hospital admissions
      among the intervention group than the control group. CONCLUSIONS: pharmacist-led
      medication review has the capacity to identify and resolve pharmaceutical care
      issues and may have some impact on the use of other health services.

PMID- 11443022
TI  - Recovery of physical function after limb injuries in independent older people
      living at home.
AB  - OBJECTIVES: to describe changes in physical functioning after fall-related
      injuries to the limbs in independently living older people. DESIGN: prospective
      cohort study, including a pre-injury assessment and post-injury assessments at 8
      weeks and 5 and 12 months. SETTING: the study is part of the larger, population
      based prospective and longitudinal Groningen Longitudinal Aging Study on the
      determinants of health-related quality of life of people aged 57 and over, who
      are living independently in the north of the Netherlands. SUBJECTS: 171 patients
      who sustained injuries at various sites on the limbs and who had completed all
      four assessments (66% of the eligible population). Patients were grouped
      according to injury site. OUTCOME MEASURE: self-reported grades of difficulties
      with performing basic and instrumental activities of daily living as measured by
      the Groningen Activity Restriction Scale. RESULTS: 1 year after the injury, pre
      injury (mean) levels of functioning were not regained in any of the groups
      studied. However, only those with fractures of the wrist or hip experienced a
      substantial decrease in ability to perform basic and instrumental activities of
      daily living between baseline and the final assessment. Furthermore, of the 44
      subjects with wrist fractures, seven (15.9%) needed help with at least one
      relevant activity at baseline and 18 (40.9%) at 12 months. Of the 34 subjects
      with hip fractures, four (11.8%) needed help with at least one activity at
      baseline and 18 (52.9%) at 12 months. Practically no changes were found in any of
      the groups after 5 months post-injury. CONCLUSIONS: not only hip fractures, but
      also wrist fractures may reduce older people's chances of remaining independent.
      Prospects of further recovery are minimal 5-6 months after the injury.

PMID- 11443023
TI  - Does the mini nutritional assessment predict hospitalization outcomes in older
      people?
AB  - BACKGROUND: the Mini Nutritional Assessment is a validated clinical tool for the
      assessment of nutritional status in older people. Moderate to severe malnutrition
      is common in elderly patients in hospital and is associated with a poor outcome.
      OBJECTIVES: to determine whether the Mini Nutritional Assessment can predict the
      outcome of hospital stay in older individuals. SETTING: a tertiary-care geriatric
      hospital. METHODS: we evaluated nutritional status using the Mini Nutritional
      Assessment in 1319 patients (mean age 84.2, 70% women) admitted between February
      1996 and January 1998; 1145 complete assessments were available for analysis. The
      assessment was carried out on admission and studied in relation to length of stay
      and in-hospital mortality for all patients, and discharge to a nursing home for
      those living at home before admission. RESULTS: Mini Nutritional Assessment
      scores averaged 19.9+/-3.8 (mean+/-SD) with a range of 8.0-27.5, and a median of
      20.5. A score below 17, corresponding to malnutrition, was associated with an
      almost threefold increase in mortality and in the rate of discharge to a nursing
      home; this contrasted with a score above 24, which indicates satisfactory
      nutritional status (11.3% vs 3.7%; P<0.01 and 20.3% vs 7.7%; P<0.001,
      respectively). Length of stay was longer in the low scoring group (42.0 days vs
      30.5 days; P<0.0002). CONCLUSION: Poor nutritional status as measured by the Mini
      Nutritional Assessment was associated with increased in-hospital mortality, a
      higher rate of discharge to nursing homes and a longer length of stay.

PMID- 11443024
TI  - Can skin wrinkling in a site that has received limited sun exposure be used as a
      marker of health status and biological age?
AB  - OBJECTIVES: to determine if skin wrinkling in a site that had received limited
      sun exposure may be a marker of health status and biological age. DESIGN:
      population-based, cross-sectional study. PARTICIPANTS: we evaluated the health
      status of representative samples of elderly Greek-born people living in
      Melbourne, Greeks living in rural Greece, Anglo-Celtic Australians living in
      Melbourne and Swedes living in Sweden. We carried out microtopographic assessment
      of their skin and measured plasma dehydroepiandrosterone concentrations. METHODS:
      we derived activities of daily living, well-being, memory and general health
      status scores from a cross-cultural questionnaire. We measured skin wrinkling
      using cutaneous microtopographic methods and plasma dehydroepiandrosterone by
      enzyme immuno-assay. RESULTS: skin wrinkling was positively correlated with age
      (r(s)=0.27, P<0.0001) and negatively with body mass index (r(s)=-0.19, P<0.0001).
      Therefore, all analyses were controlled for these variables. Plasma
      dehydroepiandrosterone was higher in smokers than non-smokers (2.86 vs 2.08;
      P<0.001) and men had significantly higher plasma dehydroepiandrosterone than
      women (2.74 vs 1.69; P<0.0001). In the pooled data, skin wrinkling was negatively
      associated with general health score (r(s)=-0.13, P<0.01) and activities of daily
      living score (r(s)=-0.14, P<0.05) after controlling for age, body mass index and
      smoking. These associations were more pronounced in women. Finally, those with
      the least skin wrinkling had the highest dehydroepiandrosterone level (r(s)=
      0.12, P=0.06) after adjusting for age, smoking and sex. CONCLUSION: skin
      wrinkling in a site with limited sun exposure might be used as a marker of health
      status and, to some extent, biological age--particularly for women.

PMID- 11443025
TI  - Antioxidant defences and oxidative stress markers in erythrocytes and plasma from
      normally nourished elderly Alzheimer patients.
AB  - OBJECTIVES: to investigate blood markers of oxidative stress, and enzymatic and
      non-enzymatic antioxidants in normally nourished elderly people with Alzheimer's
      disease. DESIGN: case-control study. SUBJECTS: twenty patients with Alzheimer's
      disease and 23 elderly control subjects, living at home, free from disease and
      not undergoing any treatment known to have a strong influence on blood oxidative
      stress markers or antioxidant defence systems. METHODS: we performed a
      nutritional evaluation, including anthropometric and biological measures and a 3
      day dietary record. We determined concentrations of antioxidant vitamins (alpha
      tocopherol, retinol) and malondialdehyde in plasma and erythrocytes. We also
      measured erythrocyte enzymatic activities of glutathione peroxidase and copper
      zinc superoxide dismutase. RESULTS: the two groups were similar in age, body mass
      index, dietary record and serum albumin concentration. After adjustment for age,
      sex and cardiovascular co-morbidity, mean plasma concentration of alpha
      tocopherol was lower in those with Alzheimer disease than in control subjects
      (15+/-3.5 mg/l compared with 18.2+/-3.5; P=0.002), as was the mean plasma
      concentration of retinol (0.54+/-0.2 mg/l vs 0.7+/-0.2; P=0.014). The mean
      concentration of free plasma malondialdehyde was higher in those with Alzheimer's
      disease (0.70+/-0.2 mmol/l vs 0.5+/-0.1; P=0.036). In Alzheimer disease patients,
      free plasma malondialdehyde concentrations were inversely correlated with levels
      of alpha-tocopherol (P=0.002) and retinol (P=0.025). Erythrocyte levels of
      vitamins and enzymatic activities were similar in the two groups. CONCLUSION:
      lower plasma concentrations of alpha-tocopherol and retinol in normally nourished
      elderly patients with Alzheimer's disease than in controls could suggest that
      these antioxidant vitamins had been consumed as a result of excessive production
      of free radicals.

PMID- 11443026
TI  - Eligibility criteria for elderly mentally ill continuing-care National Health
      Service patients: are they being met and do they need revision?
AB  - BACKGROUND: in 1996, the British government directed health authorities to draw
      up local eligibility criteria for National Health Service continuing health care.
      OBJECTIVES: to examine whether elderly mentally ill continuing-care National
      Health Service patients fulfilled a variety of eligibility criteria for their
      placement, and to identify the characteristics of patients who met local
      eligibility criteria. DESIGN: descriptive study. SETTING: four continuing-care
      units for elderly mentally ill patients in and around London. SUBJECTS: 67
      continuing-care inpatients. METHODS: interview with nurse carer and, where
      possible, the patient with the use of standard global, functional, behavioural
      and cognitive rating scales. We determined fulfillment of Royal College of
      Psychiatrists' guideline criteria and three local eligibility criteria for
      elderly mentally ill continuing care. We identified clinical differences between
      those eligible and ineligible. RESULTS: although there were wide variations
      between local eligibility criteria, their effects were the same. In total, 58% of
      patients fulfilled all local eligibility criteria; 42% fulfilled none. Patients
      who fulfilled local eligibility criteria scored much higher on ratings of
      aggression, activity disturbance (wandering, and purposeless and inappropriate
      activity) and paranoid and delusional ideation. Ten percent of patients fulfilled
      Royal College of Psychiatrists' criteria but not local eligibility criteria.
      CONCLUSIONS: comprehensive and unambiguous national eligibility criteria should
      be introduced to reflect clinical needs and provide equity of access.

PMID- 11443027
TI  - A comparison of the new executive functioning domains of the CAMCOG-R with
      existing tests of executive function in elderly stroke survivors.
AB  - AIM: to compare the two new executive function tests of the revised Cambridge
      Cognitive Examination (CAMCOG-R), a bedside measure of cognitive function, with
      existing neuropsychological assessments of executive function in elderly stroke
      survivors. METHODS: we assessed 83 stroke survivors at 1 and 3 months post-stroke
      with the new CAMCOG-R, the Weigl colour form sorting test and Raven's coloured
      progressive matrices. We assessed functional recovery with the Barthel index and
      depression with the self-report 15-item geriatric depression scale. We used
      descriptive statistics, Pearson correlation coefficients, paired t-tests and
      principal axis factor analyses to interpret the data. RESULTS: the new CAMCOG-R
      executive functioning tests showed moderate correlation with the Weigl and Raven
      tests (P<0.01). Improved functional outcome as measured by the Barthel index was
      significantly associated with higher executive function test scores (P<0.05).
      Depression was significantly associated with poorer performance on all tasks of
      executive function (P<0.05). A factor analysis of the scores on all of the
      neuropsychological tests revealed a single strong factor that accounted for 66%
      of the variance. The CAMCOG-R and the executive functioning subscales used in
      this population established sensitivity to change over time. CONCLUSION: although
      the new executive tests of the CAMCOG-R compared reasonably well with the Weigl
      and Raven neuropsychological tests, the extra time taken to administer the CAMCOG
      R may not be justified. The new CAMCOG-R executive function tests were vulnerable
      to the effects of depression. Finally, the executive function tests might have
      provided more of a global measure of cognitive function, raising doubts about
      their construct validity in our patient population.

PMID- 11443028
TI  - Distal forearm fracture history in an older community-dwelling population: the
      Nottingham Community Osteoporosis (NOCOS) study.
AB  - OBJECTIVES: to assess the prevalence of a history of Colles' fracture (occurring
      after the age of 40 years) and to ascertain the extent of investigation and
      treatment of osteoporosis in this population. METHODS: we studied subjects aged >
      or =60 years from the age-sex register of three general practices. We recorded a
      history of fractures and details of any previous investigation for osteoporosis
      and treatment with bone-protective drugs. Bone mineral density was performed at
      the heel using dual-energy x-ray absorptiometry (Lunar PIXI machine). We
      classified subjects into normal, osteopaenic or osteoporotic according to the
      machine manufacturer's recommended World Health Organisation 'equivalent T-score
      thresholds' (0.6 for osteopaenia and 1.6 for osteoporosis). RESULTS: of the 605
      subjects invited, we recruited 259 women and 194 men (response rate=74.8%).
      Twenty-eight (10.8%) of the women and five (2.6%) of the men had a history of
      Colles' fracture. Of women with a prevalent Colles' fracture, 39% were
      osteoporotic and 36% were osteopaenic. These rates were significantly greater
      than in women without a Colles' fracture (19.9% osteoporotic, 29.4% osteopaenic;
      P=0.018). Assuming the same PIXI thresholds for men, two (40%) of the five men
      with a history of Colles' fractures were osteoporotic and the rest were
      osteopaenic, compared with 20.6 and 31.2% of men without a history of Colles'
      fractures. None of the subjects in the Colles' fracture group had previously been
      investigated with bone densitometry. Women with and without a history of Colles'
      fracture did not differ significantly in ever having (32.1% vs 27.2%; P=0.4) or
      currently having (14.3% vs 10.4%; P=0.4) hormone replacement treatment. None of
      the men and only one woman with a previous Colles' fracture had ever taken a non
      hormone replacement treatment for osteoporosis. CONCLUSIONS: older community
      dwelling subjects with previous Colles' fracture have a high prevalence of
      osteoporosis and are under-investigated and under-treated. Methods for
      identifying subjects with a previous Colles' fracture need to be developed in
      primary and secondary care.

PMID- 11443029
TI  - Peak flow technique and the 'windmill' trainer in older subjects admitted with
      acute airflow limitation.
AB  - METHODS: peak expiratory flow technique was assessed as being satisfactory or
      unsatisfactory in consecutive patients >60 years with an acute exacerbation of
      airflow obstruction, admitted to an integrated medical and elderly unit. RESULTS:
      at baseline assessment, 16 (25%) of 63 patients had satisfactory peak expiratory
      flow technique. After conventional teaching, this improved to 38 (60%) of 63
      (P<0.0001). Further instruction using a 'windmill' device failed to improve the
      number with a satisfactory technique.

PMID- 11443030
TI  - Is physical activity protective against hip fracture in frail older people?
AB  - BACKGROUND: there is limited evidence of a protective effect of physical activity
      in preventing hip fractures among older people living in institutions and in
      those aged 80 or over. OBJECTIVE: to examine the relationship between physical
      activity and risk of hip fracture in frail older people. DESIGN: a case-control
      study. SETTING: Auckland, New Zealand. SUBJECTS: a random sample of individuals
      hospitalized with a fracture of the femoral neck (n=911) and 910 randomly
      selected age- and sex-matched individuals from the lists of a random sample of
      general practitioners. METHODS: we sought information on physical activity and
      other potential risk factors for hip fracture from cases and controls, using a
      standardized interviewer-administered questionnaire. We conducted multivariate
      analyses, separately for those living in private homes and residential
      institutions. RESULTS: increasing hours of physical activity per week protected
      against the risk of hip fracture among individuals living in private homes,
      including those who are over 80. However, among individuals living in
      institutions, physical activity levels were extremely low (<15% participated in
      >/=2 h per week) and there was limited evidence of a protective effect.
      CONCLUSIONS: efforts to prevent hip fractures in individuals living in care homes
      and institutions should focus on passive interventions which are known to be
      effective.

PMID- 11443031
TI  - Efficacy of in-home screening for risk of functional decline.

PMID- 11443032
TI  - Rehabilitation research in frail older people.

PMID- 11443033
TI  - Predicting outcomes of proximal femoral fractures by analysis of 'get well'
      cards.

PMID- 11443034
TI  - Miller Fisher syndrome in an elderly man.

PMID- 11443035
TI  - Lonely nights in long-term care.

PMID- 11443036
TI  - Microvillar cell surface as a natural defense system against xenobiotics: a new
      interpretation of multidrug resistance.
AB  - The phenomenon of multidrug resistance (MDR) is reinterpreted on the basis of the
      recently proposed concept of microvillar signaling. According to this notion,
      substrate and ion fluxes across the surface of differentiated cells occur via
      transporters and ion channels that reside in membrane domains at the tips of
      microvilli (MV). The flux rates are regulated by the actin-based cytoskeletal
      core structure of MV, acting as a diffusion barrier between the microvillar tip
      compartment and the cytoplasm. The expression of this diffusion barrier system is
      a novel aspect of cell differentiation and represents a functional component of
      the natural defense system of epithelial cells against environmental hazardous
      ions and lipophilic compounds. Because of the specific organization of epithelial
      Ca(2+) signaling and the secretion, lipophilic compounds associated with the
      plasma membrane are transferred from the basal to the apical cell surface by a
      lipid flow mechanism. Drug release from the apical pole occurs by either direct
      secretion from the cell surface or metabolization by the microvillar cytochrome P
      450 system and efflux of the metabolites and conjugation products through the
      large multifunctional anion channels localized in apical MV. The natural
      microvillar defense system also provides a mechanistic basis of acquired MDR in
      tumor cells. The microvillar surface organization is lost in rapidly growing
      cells such as tumor or embryonic cells but is restored during exposure of tumor
      cells to cytotoxins by induction of a prolonged G(0)/G(1) resting phase.

PMID- 11443037
TI  - Pools of actin in polarized cells: some filaments are more stable than others.
      Focus on "Functionally distinct pools of actin in secretory cells".

PMID- 11443038
TI  - Functional modeling of tight junctions in intestinal cell monolayers using
      polyethylene glycol oligomers.
AB  - Despite significant advances in the characterization of tight junction (TJ)
      proteins, little is known about how molecular changes relate to function due
      primarily to the limitations of conventional paracellular probes. To address
      this, the paracellular pathway in Caco-2 and T84 cell lines was profiled by
      measuring the permeabilities of 24 polyethylene glycols (PEG) of increasing
      molecular radius (3.5--7.4 A) analyzed by mass spectrometry. When combined with a
      paracellular sieving model, these data provided quantitative descriptors of the
      pathway under control conditions and after exposure to TJ modulators. PEG
      profiles in both cell lines conformed to a biphasic process involving a
      restrictive pore (radius 4.3--4.5 A) and a nonrestrictive component responsible
      for permeability of larger molecules. PEG profiling revealed significant
      differences between the effects of EGTA and sodium caprate (C10). The restrictive
      component of EGTA-treated cells lost all size discrimination due to an increase
      in pore radius. Sodium caprate had no effect on pore radius but increased
      permeability via a different mechanism possibly involving increased numbers of
      functional pores. PEG profiling provides a useful tool for probing the functional
      regulation of the paracellular route.

PMID- 11443039
TI  - Resistance training improves single muscle fiber contractile function in older
      women.
AB  - The purpose of this study was to 1) examine single cell contractile mechanics of
      skeletal muscle before and after 12 wk of progressive resistance training (PRT)
      in older women (n = 7; 74 +/- 2 yr) and 2) to compare these results to our
      previously completed single cell PRT work with older men (n = 7; 74 +/- 2 yr)
      (Trappe S, Williamson D, Godard M, Porter D, Rowden G, and Costill D. J Applied
      Physiol 89:143--152, 2000). Knee extensor PRT was performed 3 days/wk at 80% of
      one-repetition maximum. Muscle biopsies were obtained from the vastus lateralis
      before and after the PRT. Chemically skinned single muscle fibers (n = 313) were
      studied at 15 degrees C for peak tension (P(o)), unloaded shortening velocity
      (V(o)), and power. Due to the low number of hybrid fibers identified post-PRT,
      direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter
      increased 24% (90 +/- 2 to 112 +/- 6 microm; P < 0.05) in MHC I fibers with no
      change in MHC IIa fibers. P(o) increased (P < 0.05) 33% in MHC I (0.76 +/- 0.04
      to 1.01 +/- 0.09 mN) and 14% in MHC IIa (0.73 +/- 0.04 to 0.83 +/- 0.05 mN)
      fibers. Muscle fiber V(o) was unaltered in both fiber types with PRT. MHC I and
      IIa fiber power increased (P < 0.05) 50% [11 +/- 2 to 17 +/- 2 microN. fiber
      length (FL). s(-1)] and 25% (40 +/- 8 to 51 +/- 6 microN. FL. s(-1)),
      respectively. However, when peak power was normalized to cell size, no pre- to
      postimprovements were observed. These data indicate that PRT in elderly women
      increases muscle cell size, strength, and peak power in both slow and fast muscle
      fibers, which was similar to the older men. However, in contrast to the older
      men, no change in fiber V(o) or normalized power was observed in the older women.
      These data suggest that older men and women respond differently at the muscle
      cell level to the same resistance-training stimulus.

PMID- 11443040
TI  - Functionally distinct pools of actin in secretory cells.
AB  - Acid secretion by the gastric parietal cell is controlled through movement of
      vesicles containing the proton pump, the H(+)-K(+)-ATPase (HK). We have used
      latrunculin B (Lat B), which binds to monomeric actin, to investigate actin
      turnover in the stimulated parietal cell. In isolated gastric glands, relatively
      high concentrations of Lat B were required to inhibit acid accumulation (ED(50)
      approximately 70 microM). Cultured parietal cells stimulated in the presence of
      low Lat B (0.1--1 microM) have reduced lamellipodia formation and some aberrant
      punctate phalloidin-stained structures, but translocation of HK and vacuolar
      swelling appeared unaffected. High Lat B (10--50 microM) resulted in gross
      changes in actin organization (punctate phalloidin-stained structures throughout
      the cell and nucleus) and reduced translocation of HK and vacuolar swelling.
      Resting parietal cells treated with high Lat B showed minor effects on morphology
      and F-actin staining. If resting cells treated with high Lat B were washed
      immediately before stimulation, they exhibited a normal stimulated morphology.
      These data suggest distinct pools of parietal cell actin: a pool highly
      susceptible to Lat B primarily involved in motile function of cultured cells; and
      a Lat B-resistant pool, most likely microvillar filaments, that is essential for
      secretion. Furthermore, the stimulation process appears to accentuate the effects
      of Lat B, most likely through Lat B binding to monomer actin liberated by the
      turnover of the motile actin filament pool.

PMID- 11443041
TI  - Mechanisms of reduced SR Ca(2+) release induced by inorganic phosphate in rat
      skeletal muscle fibers.
AB  - The effects of inorganic phosphate (P(i)) on Ca(2+) release from the sarcoplasmic
      reticulum (SR) were studied in mechanically skinned rat skeletal muscle fibers.
      Application of caffeine or T-tubule depolarization was used to induce Ca(2+)
      release from the SR, which was detected using fura 2 fluorescence. Addition of
      P(i) (1-40 mM) caused a reversible and concentration-dependent reduction in the
      caffeine-induced Ca(2+) transient. This effect was apparent at low P(i)
      concentration (<5 mM), which did not result in detectable precipitation of
      calcium phosphate within the SR. The inhibitory effect of P(i) exhibited a marked
      dependence on free Mg(2+) concentration. At 0.5 mM free Mg(2+), 5 mM P(i) reduced
      the caffeine-induced transient by 25.1 +/- 4.1% (n = 13). However, at 1.5 mM free
      Mg(2+), 5 mM P(i) reduced the amplitude of caffeine-induced Ca(2+) transients by
      68.9 +/- 3.1% (n = 10). Depolarization-induced SR Ca(2+) release was similarly
      affected. These effects of P(i) may be important in skeletal muscle fatigue, if
      an inhibitory action of P(i) on SR Ca(2+) release is augmented by the rise in
      cytosolic Mg(2+) concentration, which accompanies ATP breakdown.

PMID- 11443042
TI  - Energy dependence of restitution in the gastric mucosa.
AB  - Rapid epithelial repair (restitution) after injury is required to maintain
      barrier function of the gastrointestinal mucosa and skin and is thought to be a
      highly ATP-dependent process that would be inhibited under hypoxic conditions.
      However, little is known about the metabolic pathways required for restitution.
      Thus, this study was undertaken to evaluate, in vitro, the role of oxidative
      respiration and glycolysis in restitution after injury. To this end, restitution
      of the bullfrog gastric mucosa was evaluated under the following conditions: 1)
      blockade of mitochondrial respiration; 2) blockade of glycolysis; or 3) absence
      of glucose. The extent of mucosal repair after injury was evaluated by
      electrophysiology and morphology. Cell migration, repolarization, and the
      formation of tight junctions after injury occurred during blockade of
      mitochondrial respiration, whereas the recovery of mucosal barrier function did
      not. In contrast, glycolytic inhibition completely blocked all aspects of
      restitution by inhibiting the migration of surface epithelial cells. Restitution
      occurred in tissues incubated with glucose-free solutions, suggesting that cells
      contain sufficient glucose (glycogen) to drive glycolysis for many hours. Our
      results demonstrate that the glycolytic pathway is essential for restitution
      after injury in the bullfrog gastric mucosa and that all but complete repair of
      barrier function occurs in the absence of mitochondrial respiration.

PMID- 11443043
TI  - Intravascular pressure regulates local and global Ca(2+) signaling in cerebral
      artery smooth muscle cells.
AB  - The regulation of intracellular Ca(2+) signals in smooth muscle cells and
      arterial diameter by intravascular pressure was investigated in rat cerebral
      arteries (approximately 150 microm) using a laser scanning confocal microscope
      and the fluorescent Ca(2+) indicator fluo 3. Elevation of pressure from 10 to 60
      mmHg increased Ca(2+) spark frequency 2.6-fold, Ca(2+) wave frequency 1.9-fold,
      and global intracellular Ca(2+) concentration ([Ca(2+)](i)) 1.4-fold in smooth
      muscle cells, and constricted arteries. Ryanodine (10 microM), an inhibitor of
      ryanodine-sensitive Ca(2+) release channels, or thapsigargin (100 nM), an
      inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, abolished sparks and
      waves, elevated global [Ca(2+)](i), and constricted pressurized (60 mmHg)
      arteries. Diltiazem (25 microM), a voltage-dependent Ca(2+) channel (VDCC)
      blocker, significantly reduced sparks, waves, and global [Ca(2+)](i), and dilated
      pressurized (60 mmHg) arteries. Steady membrane depolarization elevated Ca(2+)
      signaling similar to pressure and increased transient Ca(2+)-sensitive K(+)
      channel current frequency e-fold for approximately 7 mV, and these effects were
      prevented by VDCC blockers. Data are consistent with the hypothesis that pressure
      induces a steady membrane depolarization that activates VDCCs, leading to an
      elevation of spark frequency, wave frequency, and global [Ca(2+)](i). In
      addition, pressure induces contraction via an elevation of global [Ca(2+)](i),
      whereas the net effect of sparks and waves, which do not significantly contribute
      to global [Ca(2+)](i) in arteries pressurized to between 10 and 60 mmHg, is to
      oppose contraction.

PMID- 11443044
TI  - Localization of endogenous and recombinant Na(+)-driven anion exchanger protein
      NDAE1 from Drosophila melanogaster.
AB  - Na(+)-dependent Cl(-)/HCO exchange activity helps maintain intracellular pH
      (pH(i)) homeostasis in many invertebrate and vertebrate cell types. Our
      laboratory cloned and characterized a Na(+)-dependent Cl(-)/HCO exchanger (NDAE1)
      from Drosophila melanogaster (Romero MF, Henry D, Nelson S, Harte PJ, and
      Sciortino CM. J Biol Chem 275: 24552--24559, 2000). In the present study we used
      immunohistochemical and Western blot techniques to characterize the developmental
      expression, subcellular localization, and tissue distribution of NDAE1 protein in
      D. melanogaster. We have shown that a polyclonal antibody raised against the
      NH(2) terminus of NDAE1 (alpha CWR57) recognizes NDAE1 electrophysiologically
      characterized in Xenopus oocytes. Moreover, our results begin to delineate the
      NDAE1 topology, i.e., both the NH(2) and COOH termini are intracellular. NDAE1 is
      expressed throughout Drosophila development in the central and peripheral nervous
      systems, sensilla, and the alimentary tract (Malpighian tubules, gut, and
      salivary glands). Coimmunolabeling of larval tissues with NDAE1 antibody and a
      monoclonal antibody to the Na(+)-K(+)-ATPase alpha-subunit revealed that the
      majority of NDAE1 is located at the basolateral membranes of Malpighian tubule
      cells. These results suggest that NDAE1 may be a key pH(i) regulatory protein and
      may contribute to basolateral ion transport in epithelia and nervous system of
      Drosophila.

PMID- 11443045
TI  - Differential contribution of sialic acid to the function of repolarizing K(+)
      currents in ventricular myocytes.
AB  - We investigated the contribution of sialic acid residues to the K(+) currents
      involved in the repolarization of mouse ventricular myocytes. Ventricular K(+)
      currents had a rapidly inactivating component followed by slowly decaying and
      sustained components. This current was produced by the summation of three
      distinct currents: I(to), which contributed to the transient component; I(ss),
      which contributed to the sustained component; and I(K,slow), which contributed to
      both components. Incubation of ventricular myocytes with the sialidase
      neuraminidase reduced the amplitude of I(to) without altering I(K,slow) and
      I(ss). We found that the reduction in I(to) amplitude resulted from a
      depolarizing shift in the voltage of activation and a reduction in the
      conductance of I(to). Expression of Kv4.3 channels, a major contributor to I(to)
      in the ventricle, in a sialylation-deficient Chinese hamster ovary cell line
      (lec2) mimicked the effects of neuraminidase on the ventricular I(to).
      Furthermore, we showed that sialylated glycolipids have little effect on the
      voltage dependence of I(to). Finally, consistent with its actions on I(to),
      neuraminidase produced an increase in the duration of the action potential of
      ventricular myocytes and the frequency of early afterdepolarizations. We conclude
      that sialylation of the proteins forming Kv4 channels is important in determining
      the voltage dependence and conductance of I(to) and that incomplete glycosylation
      of these channels could lead to arrhythmias.

PMID- 11443046
TI  - Focal adhesion kinase signaling is decreased in polyamine-depleted IEC-6 cells.
AB  - Polyamines are essential to the migration of epithelial cells in the intestinal
      mucosa. Cells depleted of polyamines do not attach as rapidly to the
      extracellular matrix and do not form the actin stress fibers essential for
      migration. Because both attachment and stress fiber formation depend on integrin
      signaling and the formation of focal adhesions, we examined these and related
      processes in polyamine-depleted IEC-6 cells. There was general decreased tyrosine
      phosphorylation of focal adhesion kinase (FAK), and, specifically, decreased
      phosphorylation of Tyr-925, the paxillin binding site. In control cells, FAK
      phosphorylation was rapid after attachment to the extracellular matrix, while
      attached cells depleted of polyamines had significantly delayed phosphorylation.
      FAK activity was also significantly inhibited in polyamine-depleted cells as was
      the phosphorylation of paxillin. Polyamine-depleted cells failed to spread
      normally after attachment, and immunocytochemistry showed little colocalization
      of FAK and actin compared with controls. Focal adhesion complex formation was
      greatly reduced in the absence of polyamines. These data suggest that defective
      integrin signaling may, at least in part, account for the decreased rates of
      attachment, actin stress fiber formation, spreading, and migration observed in
      polyamine-depleted cells.

PMID- 11443047
TI  - Dual trafficking of Slit3 to mitochondria and cell surface demonstrates novel
      localization for Slit protein.
AB  - Drosophila slit is a secreted protein involved in midline patterning. Three
      vertebrate orthologs of the fly slit gene, Slit1, 2, and 3, have been isolated.
      Each displays overlapping, but distinct, patterns of expression in the developing
      vertebrate central nervous system, implying conservation of function. However,
      vertebrate Slit genes are also expressed in nonneuronal tissues where their
      cellular locations and functions are unknown. In this study, we characterized the
      cellular distribution and processing of mammalian Slit3 gene product, the least
      evolutionarily conserved of the vertebrate Slit genes, in kidney epithelial
      cells, using both cellular fractionation and immunolabeling. Slit3, but not
      Slit2, was predominantly localized within the mitochondria. This localization was
      confirmed using immunoelectron microscopy in cell lines and in mouse kidney
      proximal tubule cells. In confluent epithelial monolayers, Slit3 was also
      transported to the cell surface. However, we found no evidence of Slit3
      proteolytic processing similar to that seen for Slit2. We demonstrated that Slit3
      contains an NH(2)-terminal mitochondrial localization signal that can direct a
      reporter green fluorescent protein to the mitochondria. The equivalent region
      from Slit1 cannot elicit mitochondrial targeting. We conclude that Slit3 protein
      is targeted to and localized at two distinct sites within epithelial cells: the
      mitochondria, and then, in more confluent cells, the cell surface. Targeting to
      both locations is driven by specific NH(2)-terminal sequences. This is the first
      examination of Slit protein localization in nonneuronal cells, and this study
      implies that Slit3 has potentially unique functions not shared by other Slit
      proteins.

PMID- 11443048
TI  - Increased neuronal excitability and seizures in the Na(+)/H(+) exchanger null
      mutant mouse.
AB  - Mice lacking the Na(+)/H(+) exchanger isoform 1 (NHE1) manifest neurological
      diseases that include ataxia, motor deficits, and a seizure disorder. The
      molecular basis for the phenotype has not been clear, and it has not been
      determined how the lack of NHE1 leads, in particular, to the seizure disorder. We
      have shown in this work that hippocampal CA1 neurons in mutant mice have a much
      higher excitability than in wild-type mice. This higher excitability is partly
      based on an upregulation of the Na(+) current density (608.2 +/- 123.2 pA/pF in
      NHE1 mutant vs. 334.7 +/- 63.7 pA/pF in wild type in HCO/CO(2)). Alterations in
      Na(+) channel characteristics, including steady-state inactivation (shift of 18
      mV in the depolarization direction in the mutant), recovery from inactivation
      (tau(h) = 5.22 +/- 0.49 ms in wild-type neurons and 2.20 +/- 0.20 ms in mutant
      neurons), and deactivation (at -100 mV, tau(d) = 1.75 +/- 0.53 ms in mutant and
      0.21 +/- 0.05 ms in wild-type neurons) further enhance the differences in
      excitability between mutant and wild-type mice. Our investigation demonstrates
      the existence of an important functional interaction between the NHE1 protein and
      the voltage-sensitive Na(+) channel. We hypothesize that the increased neuronal
      excitability and possibly the seizure disorder in mice lacking the NHE1 is due,
      at least in part, to changes in Na(+) channel expression and/or regulation.

PMID- 11443049
TI  - Epidermal growth factor regulation of rat NHE2 gene expression.
AB  - Epidermal growth factor (EGF) is involved in acute regulation of Na(+)/H(+)
      exchangers (NHEs), but the effect of chronic EGF administration on NHE gene
      expression is unknown. The present studies showed that EGF treatment increased
      NHE2-mediated intestinal brush-border membrane vesicle Na(+) absorption and NHE2
      mRNA abundance by nearly twofold in 19-day-old rats. However, no changes were
      observed in renal NHE2 mRNA or intestinal and renal NHE3 mRNA abundance. To
      understand the mechanism of this regulation, we developed the rat intestinal
      epithelial (RIE) cell as an in vitro model to study the effect of EGF on NHE2
      gene expression. EGF increased functional NHE2 activity and mRNA abundance in
      cultured RIE cells, and this stimulation could be blocked by actinomycin D (a
      transcriptional inhibitor). Additionally, NHE2 promoter reporter gene assays in
      transiently transfected RIE cells showed an almost twofold increase in promoter
      activity after EGF treatment. We conclude that rat NHE2 activity can be
      stimulated by chronic EGF treatment and that this response is at least partially
      mediated by gene transcription.

PMID- 11443050
TI  - Negative regulation of ligand-initiated Ca(2+) uptake by PKC-beta II in
      differentiated HL60 cells.
AB  - In phagocytic cells, fMet-Leu-Phe triggers phosphoinositide remodeling,
      activation of protein kinase C (PKC), release of intracellular Ca(2+) and uptake
      of extracellular Ca(2+). Uptake of extracellular Ca(2+) can be triggered by store
      operated Ca(2+) channels (SOCC) and via a receptor-operated nonselective cation
      channel(s). In neutrophilic HL60 cells, the PKC activator phorbol myristate
      acetate (PMA) activates multiple PKC isotypes, PKC-alpha, PKC-beta, and PKC
      delta, and inhibits ligand-initiated mobilization of intracellular Ca(2+) and
      uptake of extracellular Ca(2+). Therefore PKC is a negative regulator at several
      points in Ca(2+) mobilization. In contrast, selective depletion of PKC-beta in
      HL60 cells by an antisense strategy enhanced fMet-Leu-Phe-initiated Ca(2+) uptake
      but not mobilization of intracellular Ca(2+). Thapsigargin-induced Ca(2+) uptake
      through SOCC was not affected by PKC-beta II depletion. Thus PKC-beta II is a
      selective negative regulator of Ca(2+) uptake but not release of intracellular
      Ca(2+) stores. PKC-beta II inhibits a receptor-operated cation or Ca(2+) channel,
      thus inhibiting ligand-initiated Ca(2+) uptake.

PMID- 11443051
TI  - Key role for constitutive cyclooxygenase-2 of MDCK cells in basal signaling and
      response to released ATP.
AB  - Madin-Darby canine kidney (MDCK) cells release ATP upon mechanical or biochemical
      activation, initiating P2Y receptor signaling that regulates basal levels of
      multiple second messengers, including cAMP (J Biol Chem 275: 11735--11739, 2000).
      Data shown here document inhibition of cAMP formation by Gd(3+) and niflumic
      acid, channel inhibitors that block ATP release. cAMP production is stimulated
      via Ca(2+)-dependent activation of cytosolic phospholipase A(2), release of
      arachidonic acid (AA), and cyclooxygenase (COX)-dependent production of
      prostaglandins, which activate prostanoid receptors coupled to G(s) and adenylyl
      cyclase. In the current investigation, we assessed the expression and functional
      role of the two known isoforms of COX, COX-1 and COX-2. Treatment of cells with
      either a COX-1-selective inhibitor, SC-560, or COX-2-selective inhibitors, SC
      58125 or NS-398, inhibited basal and UTP-stimulated cAMP levels. COX inhibitors
      also decreased forskolin-stimulated cAMP formation, implying this response is in
      part attributable to an action of AA metabolites. These findings imply an
      important role for the inducible form of COX, COX-2, under basal conditions.
      Indeed, COX-2 expression was readily detectable by immunoblot, and treatments
      that induce or reduce COX-2 expression in other cells (interleukin-1beta, tumor
      necrosis factor-alpha, phorbol ester, or dexamethasone) had minimal or no effect
      on the levels of COX-2 immunoreactivity. RT-PCR using isoform-specific primers
      detected COX-2 mRNA. We conclude that COX-2 is constitutively expressed in MDCK
      D(1) cells and participates in basal and P2Y(2)-mediated signaling, implying a
      key role for COX-2 in regulation of epithelial cell function.

PMID- 11443052
TI  - Identification of mediators stimulating proliferation and matrix synthesis of rat
      pancreatic stellate cells.
AB  - The aim of this study was to identify fibrogenic mediators stimulating
      activation, proliferation, and/or matrix synthesis of rat pancreatic stellate
      cells (PSC). PSC were isolated from the pancreas of normal Wistar rats and from
      rats with cerulein pancreatitis. Cell activation was demonstrated by
      immunofluorescence microscopy of smooth muscle alpha-actin (SMA) and real-time
      quantitative RT-PCR of SMA, fibronectin, and transforming growth factor (TGF)
      beta(1). Proliferation was measured by bromodeoxyuridine incorporation. Matrix
      synthesis was demonstrated on the protein and mRNA level. Within a few days in
      primary culture, PSC changed their phenotype from fat-storing to SMA-positive
      myofibroblast-like cells expressing platelet-derived growth factor (PDGF) alpha-
      and PDGF beta-receptors. TGF-beta(1) and tumor necrosis factor (TNF)-alpha
      accelerated the change in the cells' phenotype. Addition of 50 ng/ml PDGF and 5
      ng/ml basic fibroblast growth factor (bFGF) to cultured PSC significantly
      stimulated cell proliferation (4.37 +/- 0.49- and 2.96 +/- 0.39-fold of control).
      Fibronectin synthesis calculated on the basis of DNA was stimulated by 5 ng/ml
      bFGF (3.44 +/- 1.13-fold), 5 ng/ml TGF-beta(1) (2.46 +/- 0.89-fold), 20 ng/ml
      PDGF (2.27 +/- 0.68-fold), and 50 ng/ml TGF-alpha (1.87 +/- 0.19-fold). As shown
      by RT-PCR, PSC express predominantly the splice variant EIII-A of fibronectin.
      Immunofluorescence microscopy and Northern blot confirmed that in particular bFGF
      and TGF-beta(1) stimulated the synthesis of fibronectin and collagens type I and
      III. In conclusion, our data demonstrate that 1) TGF-beta(1) and TNF-alpha
      accelerate the change in the cell phenotype, 2) PDGF represents the most
      effective mitogen, and 3) bFGF, TGF-beta(1), PDGF, and, to a lesser extent, TGF
      alpha stimulate extracellular matrix synthesis of cultured rat PSC.

PMID- 11443053
TI  - Signaling by eNOS through a superoxide-dependent p42/44 mitogen-activated protein
      kinase pathway.
AB  - Expression of endothelial nitric oxide synthase (eNOS) in transfected U-937 cells
      upregulates phorbol 12-myristate 13-acetate (PMA)-induced tumor necrosis factor
      alpha (TNF-alpha) production through a superoxide (O(2)(-))-dependent mechanism.
      Because mitogen-activated protein kinases (MAPK) have been shown to participate
      in both reactive oxygen species signaling and TNF-alpha regulation, their
      possible role in eNOS-derived O(2)(-) signal transduction was examined. A redox
      cycling agent, phenazine methosulfate, was found to both upregulate TNF-alpha
      (5.8 +/- 1.0 fold; P = 0.01) and increase the phosphorylation state of p42/44
      MAPK (3.1 +/- 0.2 fold; P = 0.01) in PMA-differentiated U-937 cells. Although S
      nitroso-N-acetylpenicillamine, a nitric oxide (NO) donor, also increased TNF
      alpha production, NO exposure led to phosphorylation of p38 MAPK, not p42/44
      MAPK. Upregulation of TNF-alpha production by eNOS transfection was associated
      with increases in activated p42/44 MAPK (P = 0.001), whereas levels of
      phosphorylated p38 MAPK were unaffected. Furthermore, cotransfection with Cu/Zn
      superoxide dismutase, which blocks TNF-alpha upregulation by eNOS, also abolished
      the effects on p42/44 MAPK. Expression of Gln(361)eNOS, a mutant that produces
      O(2)(-) but not NO, still resulted in p42/44 MAPK phosphorylation. In contrast,
      two NADPH binding site deletion mutants of eNOS that lack oxidase activity had no
      effect on p42/44 MAPK. Finally, PD-98059, a p42/44 MAPK pathway inhibitor,
      blocked TNF-alpha upregulation by eNOS (P = 0.02). Thus O(2)(-) produced by eNOS
      increases TNF-alpha production via a mechanism that involves p42/44 MAPK
      activation.

PMID- 11443054
TI  - Hypotonic swelling-induced Ca(2+) release by an IP(3)-insensitive Ca(2+) store.
AB  - Hypotonic swelling increases the intracellular Ca(2+) concentration ([Ca(2+)](i))
      in vascular smooth muscle cells (VSMC). The source of this Ca(2+) is not clear.
      To study the source of increase in [Ca(2+)](i) in response to hypotonic swelling,
      we measured [Ca(2+)](i) in fura 2-loaded cultured VSMC (A7r5 cells). Hypotonic
      swelling produced a 40.7-nM increase in [Ca(2+)](i) that was not inhibited by
      EGTA but was inhibited by 1 microM thapsigargin. Prior depletion of inositol
      1,4,5-trisphosphate (IP(3))-sensitive Ca(2+) stores with vasopressin did not
      inhibit the increase in [Ca(2+)](i) in response to hypotonic swelling. Exposure
      of (45)Ca(2+)-loaded intracellular stores to hypotonic swelling in permeabilized
      VSMC produced an increase in (45)Ca(2+) efflux, which was inhibited by 1 microM
      thapsigargin but not by 50 microg/ml heparin, 50 microM ruthenium red, or 25
      microM thio-NADP. Thus hypotonic swelling of VSMC causes a release of Ca(2+) from
      the intracellular stores from a novel site distinct from the IP(3)-, ryanodine-,
      and nicotinic acid adenine dinucleotide phosphate-sensitive stores.

PMID- 11443055
TI  - p38 MAPK mediates renal tubular cell TNF-alpha production and TNF-alpha-dependent
      apoptosis during simulated ischemia.
AB  - Ischemia causes renal tubular cell loss through apoptosis; however, the
      mechanisms of this process remain unclear. Using the renal tubular epithelial
      cell line LLC-PK(1), we developed a model of simulated ischemia (SI) to
      investigate the role of p38 MAPK (mitogen-activated protein kinase) in renal cell
      tumor necrosis factor-alpha (TNF-alpha) mRNA production, protein bioactivity, and
      apoptosis. Results demonstrate that 60 min of SI induced maximal TNF-alpha mRNA
      production and bioactivity. Furthermore, 60 min of ischemia induced renal tubular
      cell apoptosis at all substrate replacement time points examined, with peak
      apoptotic cell death occurring after either 24 or 48 h. p38 MAPK inhibition
      abolished TNF-alpha mRNA production and TNF-alpha bioactivity, and both p38 MAPK
      inhibition and TNF-alpha neutralization (anti-porcine TNF-alpha antibody)
      prevented apoptosis after 60 min of SI. These results constitute the initial
      demonstration that 1) renal tubular cells produce TNF-alpha mRNA and biologically
      active TNF-alpha and undergo apoptosis in response to SI, and 2) p38 MAPK
      mediates renal tubular cell TNF-alpha production and TNF-alpha-dependent
      apoptosis after SI.

PMID- 11443056
TI  - Rho activation in excitatory agonist-stimulated vascular smooth muscle.
AB  - Small GTPase Rho and its downstream effector, Rho kinase, have been implicated in
      agonist-stimulated Ca(2+) sensitization of 20-kDa myosin light chain (MLC(20))
      phosphorylation and contraction in smooth muscle. In the present study we
      demonstrated for the first time that excitatory receptor agonists induce
      increases in amounts of an active GTP-bound form of RhoA, GTP-RhoA, in rabbit
      aortic smooth muscle. Using a pull-down assay with a recombinant RhoA-binding
      protein, Rhotekin, we found that a thromboxane A(2) mimetic, U-46619, which
      induced a sustained contractile response, induced a sustained rise in the amount
      of GTP-RhoA in a dose-dependent manner with an EC(50) value similar to that for
      the contractile response. U-46619-induced RhoA activation was thromboxane A(2)
      receptor-mediated and reversible. Other agonists including norepinephrine,
      serotonin, histamine, and endothelin-1 (ET-1) also stimulated RhoA, albeit to
      lesser extents than U-46619. In contrast, ANG II and phorbol 12,13-dibutyrate
      failed to increase GTP-RhoA. The tyrosine kinase inhibitor genistein
      substantially inhibited RhoA activation by these agonists, except for ET-1. Thus
      excitatory agonists induce Rho activation in an agonist-specific manner, which is
      thought to contribute to stimulation of MLC(20) phosphorylation Ca(2+)
      sensitivity.

PMID- 11443057
TI  - Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth
      muscle.
AB  - Vasoconstrictors activate the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 in rat aortic
      smooth muscle, but the mechanism is unknown. Efflux of (86)Rb(+) from rat aorta
      in response to phenylephrine (PE) was measured in the absence and presence of
      bumetanide, a specific inhibitor of NKCC1. Removal of extracellular Ca(2+)
      completely abolished the activation of NKCC1 by PE. This was not due to
      inhibition of Ca(2+)-dependent K(+) channels since blocking these channels with
      Ba(2+) in Ca(2+)-replete solution did not prevent activation of NKCC1 by PE.
      Stimulation of NKCC1 by PE was inhibited 70% by 75 microM ML-9, 97% by 2 microM
      wortmannin, and 70% by 2 mM 2,3-butanedione monoxime, each of which inhibited
      isometric force generation in aortic rings. Bumetanide-insensitive Rb(+) efflux,
      an indication of Ca(2+)-dependent K(+) channel activity, was reduced by ML-9 but
      not by the other inhibitors. Stretching of aortic rings on tubing to increase
      lumen diameter to 120% of normal almost completely blocked the stimulation of
      NKCC1 by PE without inhibiting the stimulation by hypertonic shrinkage. We
      conclude that activation of the Na(+)-K(+)-2Cl(-) cotransporter by PE is the
      direct result of smooth muscle contraction through Ca(2+)-dependent activation of
      myosin light chain kinase. This indicates that the Na(+)-K(+)-2Cl(-)
      cotransporter is regulated by the contractile state of vascular smooth muscle.

PMID- 11443058
TI  - Response to caffeine and ryanodine receptor isoforms in mouse skeletal muscles.
AB  - The response to caffeine was studied in mouse muscles [diaphragm, soleus, and
      extensor digitorum longus (EDL)] with different ryanodine receptor isoform (RyR1,
      RyR3) composition and in single permeabilized muscle fibers dissected from
      diaphragm of wild-type (WT) and RyR3-deficient (RyR3-/-) mice at 1, 15, 30, and
      60 postnatal days (PND). The caffeine response decreased during development, and,
      in adult mice, was greater in diaphragm, lower in EDL, and intermediate in
      soleus. This suggests a direct relation between response to caffeine and RyR3
      expression. The lack of RyR3 reduced caffeine response in young, but not in adult
      mice, and did not abolish the age-dependent variation and the intermuscle
      differences. In diaphragm single fibers, the response to caffeine increased
      during development and was reduced in fibers lacking RyR3 both at 15 and 60 PND.
      A population of fibers highly responsive to caffeine was present in adult WT and
      disappeared in RyR3-/-. The results confirm the contribution of RyR3 to calcium
      release for contractile response and clarify the contribution of RyR3 to
      developmental changes and intermuscle differences.

PMID- 11443059
TI  - Rabbit conjunctival epithelium transports fluid, and P2Y2(2) receptor agonists
      stimulate Cl(-) and fluid secretion.
AB  - Rabbit conjunctival epithelium exhibits UTP-dependent Cl(-) secretion into the
      tears. We investigated whether fluid secretion also takes place. Short-circuit
      current (I(sc)) was 14.9 +/- 1.4 microA/cm(2) (n = 16). Four P2Y(2) purinergic
      receptor agonists [UTP and the novel compounds INS365, INS306, and INS440
      (Inspire Pharmaceuticals)] added apically (10 microM) resulted in temporary
      (approximately 30 min) I(sc) increases (88%, 66%, 57%, and 28%, respectively; n =
      4 each). Importantly, the conjunctiva transported fluid from serosa to mucosa at
      a rate of 6.5 +/- 0.7 microl x h(-1) x cm(-2) (range 2.1--15.3, n = 20). Fluid
      transport was stimulated by mucosal additions of 10 microM: 1) UTP, from 7.4 +/-
      2.3 to 10.7 +/- 3.3 microl x h(-1) x cm(-2), n = 5; and 2) INS365, from 6.3 +/-
      1.0 to 9.8 +/- 2.5 microl. h(-1) x cm(-2), n = 5. Fluid transport was abolished
      by 1 mM ouabain (n = 5) and was drastically inhibited by 300 microM quinidine
      (from 6.4 +/- 1.2 to 3.6 +/- 1.0 microl x h(-1) x cm(-2), n = 4). We conclude
      that this epithelium secretes fluid actively and that P2Y(2) agonists stimulate
      both Cl(-) and fluid secretions.

PMID- 11443060
TI  - A role for MAP kinase in regulating ectodomain shedding of APLP2 in corneal
      epithelial cells.
AB  - We previously reported an increased secretion of amyloid precursor-like protein 2
      (APLP2) in the healing corneal epithelium. The present study sought to
      investigate signal transduction pathways involved in APLP2 shedding in vitro.
      APLP2 was constitutively shed and released into culture medium in SV40
      immortalized human corneal epithelial cells as assessed by Western blotting, flow
      cytometry, and indirect immunofluorescence. Activation of protein kinase C (PKC)
      by phorbol 12-myristate 13-acetate (PMA) caused significant increases in APLP2
      shedding. This was inhibited by staurosporine and a PKC-epsilon-specific, N
      myristoylated peptide inhibitor. Epidermal growth factor (EGF) also induced APLP2
      accumulation in culture medium. Basal APLP2 shedding as well as that induced by
      PMA and EGF was blocked by a mitogen-activated protein kinase (MAPK) kinase
      inhibitor, U-0126. Our results suggest that MAPK activity accounts for basal as
      well as PKC- and EGF-induced APLP2 shedding. In addition, PKC-epsilon may be
      involved in the induction of APLP2 shedding in corneal epithelial cells.

PMID- 11443061
TI  - Alterations in airway ion transport in NKCC1-deficient mice.
AB  - Airways of Na(+)-K(+)-2Cl(-) (NKCC1)-deficient mice (-/-) were studied in Ussing
      chambers to determine the role of the basolateral NKCC1 in transepithelial anion
      secretion. The basal short-circuit current (I(sc)) of tracheae and bronchi from
      adult mice did not differ between NKCC1-/- and normal mice, whereas NKCC1-/-
      tracheae from neonatal mice exhibited a significantly reduced basal I(sc). In
      normal mouse tracheae, sensitivity to the NKCC1 inhibitor bumetanide correlated
      inversely with the age of the mouse. In contrast, tracheae from NKCC1-/- mice at
      all ages were insensitive to bumetanide. The anion secretory response to
      forskolin did not differ between normal and NKCC1-/- tissues. However, when
      larger anion secretory responses were induced with UTP, airways from the NKCC1-/-
      mice exhibited an attenuated response. Ion substitution and drug treatment
      protocols suggested that HCO secretion compensated for reduced Cl(-) secretion in
      NKCC1-/- airway epithelia. The absence of spontaneous airway disease or pathology
      in airways from the NKCC1-/- mice suggests that the NKCC1 mutant mice are able to
      compensate adequately for absence of the NKCC1 protein.

PMID- 11443062
TI  - Characterization and imaging of A6 epithelial cell clones expressing
      fluorescently labeled ENaC subunits.
AB  - A6 model renal epithelial cells were stably transfected with enhanced green
      fluorescent protein (EGFP)-tagged alpha- or beta-subunits of the epithelial Na(+)
      channel (ENaC). Transfected RNA and proteins were both expressed in low
      abundance, similar to the endogenous levels of ENaC in native cells. In living
      cells, laser scanning confocal microscopy revealed a predominantly subapical
      distribution of EGFP-labeled subunits, suggesting a readily accessible pool of
      subunits available to participate in Na(+) transport. The basal level of Na(+)
      transport in the clonal lines was enhanced two- to fourfold relative to the
      parent line. Natriferic responses to insulin or aldosterone were similar in
      magnitude to the parent line, while forskolin-stimulated Na(+) transport was 64%
      greater than control in both the alpha- and beta-transfected lines. In response
      to forskolin, EGFP-labeled channel subunits traffic to the apical membrane. These
      data suggest that channel regulators, not the channel per se, form the rate
      limiting step in response to insulin or aldosterone stimulation, while the number
      of channel subunits is important for basal as well as cAMP-stimulated Na(+)
      transport.

PMID- 11443063
TI  - ENaC- and CFTR-dependent ion and fluid transport in mammary epithelia.
AB  - Mammary epithelial 31EG4 cells (MEC) were grown as monolayers on filters to
      analyze the apical membrane mechanisms that help mediate ion and fluid transport
      across the epithelium. RT-PCR showed the presence of cystic fibrosis
      transmembrane conductance regulator (CFTR) and epithelial Na(+) channel (ENaC)
      message, and immunomicroscopy showed apical membrane staining for both proteins.
      CFTR was also localized to the apical membrane of native human mammary duct
      epithelium. In control conditions, mean values of transepithelial potential
      (apical-side negative) and resistance (R(T)) are -5.9 mV and 829 Omega x cm(2),
      respectively. The apical membrane potential (V(A)) is -40.7 mV, and the mean
      ratio of apical to basolateral membrane resistance (R(A)/R(B)) is 2.8. Apical
      amiloride hyperpolarized V(A) by 19.7 mV and tripled R(A)/R(B). A cAMP-elevating
      cocktail depolarized V(A) by 17.6 mV, decreased R(A)/R(B) by 60%, increased short
      circuit current by 6 microA/cm(2), decreased R(T) by 155 Omega x cm(2), and
      largely eliminated responses to amiloride. Whole cell patch-clamp measurements
      demonstrated amiloride-inhibited Na(+) currents [linear current-voltage (I-V)
      relation] and forskolin-stimulated Cl(-) currents (linear I-V relation). A
      capacitance probe method showed that in the control state, MEC monolayers either
      absorbed or secreted fluid (2--4 microl x cm(-2) x h(-1)). Fluid secretion was
      stimulated either by activating CFTR (cAMP) or blocking ENaC (amiloride). These
      data plus equivalent circuit analysis showed that 1) fluid absorption across MEC
      is mediated by Na(+) transport via apical membrane ENaC, and fluid secretion is
      mediated, in part, by Cl(-) transport via apical CFTR; 2) in both cases,
      appropriate counterions move through tight junctions to maintain
      electroneutrality; and 3) interactions among CFTR, ENaC, and tight junctions
      allow MEC to either absorb or secrete fluid and, in situ, may help control
      luminal [Na(+)] and [Cl(-)].

PMID- 11443064
TI  - Regulation of epithelial transport and barrier function by distinct protein
      kinase C isoforms.
AB  - The phorbol ester phorbol 12-myristate 13-acetate (PMA) inhibits Cl(-) secretion
      (short-circuit current, I(sc)) and decreases barrier function (transepithelial
      resistance, TER) in T84 epithelia. To elucidate the role of specific protein
      kinase C (PKC) isoenzymes in this response, we compared PMA with two non-phorbol
      activators of PKC (bryostatin-1 and carbachol) and utilized three PKC inhibitors
      (Go-6850, Go-6976, and rottlerin) with different isozyme selectivity profiles.
      PMA sequentially inhibited cAMP-stimulated I(sc) and decreased TER, as measured
      by voltage-current clamp. By subcellular fractionation and Western blot, PMA (100
      nM) induced sequential membrane translocation of the novel PKC epsilon followed
      by the conventional PKC alpha and activated both isozymes by in vitro kinase
      assay. PKC delta was activated by PMA but did not translocate. By
      immunofluorescence, PKC epsilon redistributed to the basolateral domain in
      response to PMA, whereas PKC alpha moved apically. Inhibition of I(sc) by PMA was
      prevented by the conventional and novel PKC inhibitor Go-6850 (5 microM) but not
      the conventional isoform inhibitor Go-6976 (5 microM) or the PKC delta inhibitor
      rottlerin (10 microM), implicating PKC epsilon in inhibition of Cl(-) secretion.
      In contrast, both Go-6976 and Go-6850 prevented the decline of TER, suggesting
      involvement of PKC alpha. Bryostatin-1 (100 nM) translocated PKC epsilon and PKC
      alpha and inhibited cAMP-elicited I(sc). However, unlike PMA, bryostatin-1
      downregulated PKC alpha protein, and the decrease in TER was only transient.
      Carbachol (100 microM) translocated only PKC epsilon and inhibited I(sc) with no
      effect on TER. Go-6850 but not Go-6976 or rottlerin blocked bryostatin-1 and
      carbachol inhibition of I(sc). We conclude that basolateral translocation of PKC
      epsilon inhibits Cl(-) secretion, while apical translocation of PKC alpha
      decreases TER. These data suggest that epithelial transport and barrier function
      can be modulated by distinct PKC isoforms.

PMID- 11443065
TI  - MAPK p38 antagonism as a novel method of inhibiting lymphoid immune suppression
      in polymicrobial sepsis.
AB  - Although studies indicate that a shift from a Th1 to a Th2 response contributes
      to a marked suppression of cell-mediated immunity during sepsis, the mechanism by
      which this occurs remains unknown. Given that the mitogen-activated protein
      kinase (MAPK) p38 plays a critical role in the activation and function of immune
      cells, the aim of this study was to determine the contribution of MAPK p38
      activation to the immune dysfunction seen in polymicrobial sepsis. To study this,
      polymicrobial sepsis was induced in C3H/HeN male mice by cecal ligation and
      puncture (CLP). Splenic lymphocytes and purified T cells were harvested 24 h post
      CLP, pretreated with the specific MAPK p38 inhibitor SB-203580, and then
      stimulated with a monoclonal antibody against the T cell marker CD3. The results
      indicate that interleukin (IL)-2 release is markedly depressed while the release
      of the immunosuppressive mediator, IL-10, as well as mRNA levels of IL-10 and IL
      4, are augmented after CLP. Inhibition of MAPK p38 suppressed in vitro IL-10
      levels as well as IL-10 and IL-4 gene expression while restoring the release of
      IL-2. To determine whether these in vitro findings could be translated to an in
      vivo setting, mice were given 100 mg of SB-203580/kg body wt or saline vehicle
      (intraperitoneal) at 12 h post-CLP. Examination of ex vivo lymphocyte
      responsiveness indicated that, as with the in vitro finding, septic mouse Th1
      responsiveness was restored. In light of our recent finding that delayed in vivo
      SB-203580 treatment also improved survival after CLP, we believe that these
      results not only illustrate the role of MAPK p38 in the induction of
      immunosuppressive agents in sepsis but demonstrate that SB-203580 administration
      after the initial proinflammatory state of sepsis significantly prevents the
      morbidity from sepsis.

PMID- 11443066
TI  - Functional and molecular characterization of the K-Cl cotransporter of Xenopus
      laevis oocytes.
AB  - The K-Cl cotransporters (KCCs) have a broad range of physiological roles, in a
      number of cells and species. We report here that Xenopus laevis oocytes express a
      K-Cl cotransporter with significant functional and molecular similarity to
      mammalian KCCs. Under isotonic conditions, defolliculated oocytes exhibit a Cl(-)
      dependent (86)Rb(+) uptake mechanism after activation by the cysteine-reactive
      compounds N-ethylmaleimide (NEM) and mercuric chloride (HgCl(2)). The activation
      of this K-Cl cotransporter by cell swelling is prevented by inhibition of protein
      phosphatase-1 with calyculin A; NEM activation of the transporter was not blocked
      by phosphatase inhibition. Kinetic characterization reveals apparent values for
      the Michaelis-Menten constant of 27.7 +/- 3.0 and 15.4 +/- 4.7 mM for Rb(+) and
      Cl(-), respectively, with an anion selectivity for K(+) transport of Cl(-) =
      PO(4)(3-) = Br(-) > I(-) > SCN(-) > gluconate. The oocyte K-Cl cotransporter was
      sensitive to several inhibitors, including loop diuretics, with apparent half
      maximal inhibition values of 200 and 500 microM for furosemide and bumetanide,
      respectively. A partial cDNA encoding the Xenopus K-Cl cotransporter was cloned
      from oocyte RNA; the corresponding transcript is widely expressed in Xenopus
      tissues. The predicted COOH-terminal protein fragment exhibited particular
      homology to the KCC1/KCC3 subgroup of the mammalian KCCs, and the functional
      characteristics are the most similar to those of KCC1 (Mercado A, Song L, Vazquez
      N, Mount DB, and Gamba G. J Biol Chem 275: 30326--30334, 2000).

PMID- 11443067
TI  - Factor Xa is a fibroblast mitogen via binding to effector-cell protease receptor
      1 and autocrine release of PDGF.
AB  - The coagulation cascade protease thrombin is a fibroblast mitogen, but the
      proliferative potential of other coagulation proteases is not known. In this
      study we show that factor Xa stimulated human fetal lung fibroblast DNA synthesis
      in a concentration-dependent manner from 1 nM onward with a fourfold increase at
      200 nM. The mitogenic effect of factor Xa was confirmed using a colorimetric
      proliferation assay and direct cell counting. Factor Xa and thrombin had
      equivalent potencies, and their stimulatory effects followed a similar time
      course. Comparable results were also obtained with primary human adult
      fibroblasts derived from lung, kidney, heart, skin, and liver. Factor VIIa also
      stimulated fibroblast proliferation, but only at concentrations >10 nM, whereas
      factor IXa had no effect. To begin to address the mechanism by which factor Xa is
      acting, we show that human fibroblasts express effector-cell protease receptor-1
      and that blocking antibodies to this receptor and the catalytic site of factor Xa
      inhibited its mitogenic effect. Furthermore, factor Xa upregulated platelet
      derived growth factor-A (PDGF-A) mRNA expression, whereas PDGF-B could not be
      detected, and a blocking antibody to PDGF inhibited the mitogenic effect of
      factor Xa. We conclude that factor Xa acts as a fibroblast mitogen via binding to
      effector-cell protease receptor-1 and the autocrine release of PDGF.

PMID- 11443068
TI  - Stretch-activated cation channels in skeletal muscle myotubes from sarcoglycan
      deficient hamsters.
AB  - Deficiency of delta-sarcoglycan (delta-SG), a component of the dystrophin
      glycoprotein complex, causes cardiomyopathy and skeletal muscle dystrophy in
      Bio14.6 hamsters. Using cultured myotubes prepared from skeletal muscle of normal
      and Bio14.6 hamsters (J2N-k strain), we investigated the possibility that the
      delta-SG deficiency may lead to alterations in ionic conductances, which may
      ultimately lead to myocyte damage. In cell-attached patches (with Ba(2+) as the
      charge carrier), an approximately 20-pS channel was observed in both control and
      Bio14.6 myotubes. This channel is also permeable to K(+) and Na(+) but not to Cl(
      ). Channel activity was increased by pressure-induced stretch and was reduced by
      GdCl(3) (>5 microM). The basal open probability of this channel was fourfold
      higher in Bio14.6 myotubes, with longer open and shorter closed times. This was
      mimicked by depolymerization of the actin cytoskeleton. In intact Bio14.6
      myotubes, the unidirectional basal Ca(2+) influx was enhanced compared with
      control. This Ca(2+) influx was sensitive to GdCl(3), signifying that stretch
      activated cation channels may have been responsible for Ca(2+) influx in Bio14.6
      hamster myotubes. These results suggest a possible mechanism by which cell damage
      might occur in this animal model of muscular dystrophy.

PMID- 11443069
TI  - Inhibition of TASK-1 potassium channel by phospholipase C.
AB  - The two-pore-domain K(+) channel, TASK-1, was recently shown to be a target of
      receptor-mediated regulation in neurons and in adrenal glomerulosa cells. Here,
      we demonstrate that TASK-1 expressed in Xenopus laevis oocytes is inhibited by
      different Ca(2+)-mobilizing agonists. Lysophosphatidic acid, via its endogenous
      receptor, and ANG II and carbachol, via their heterologously expressed ANG II
      type 1a and M(1) muscarinic receptors, respectively, inhibit TASK-1. This effect
      can be mimicked by guanosine 5'-O-(3-thiotriphosphate), indicating the
      involvement of GTP-binding protein(s). The phospholipase C inhibitor U-73122
      reduced the receptor-mediated inhibition of TASK-1. Downstream signals of
      phospholipase C action (inositol 1,4,5-trisphosphate, cytoplasmic Ca(2+)
      concentration, and diacylglycerol) do not mediate the inhibition. Unlike the G(q)
      coupled receptors, stimulation of the G(i)-activating M(2) muscarinic receptor
      coexpressed with TASK-1 results in an only minimal decrease of the TASK-1
      current. However, additional coexpression of phospholipase C-beta(2) (which is
      responsive also to G(i) beta gamma-subunits) renders M(2) receptor activation
      effective. This indicates the significance of phospholipase C activity in the
      receptor-mediated inhibition of TASK-1.

PMID- 11443070
TI  - PI 3-kinases and Src kinases regulate spreading and migration of cultured VSMCs.
AB  - Pulmonary artery smooth muscle cell (PASMC) adhesion, spreading, and migration
      depend on matrix-stimulated reorganization of focal adhesions. Platelet-derived
      growth factor (PDGF) activates intracellular signal transduction cascades that
      also regulate adhesion, spreading, and migration, but the signaling molecules
      involved in these events are poorly defined. We hypothesized that
      phosphatidylinositol (PI) 3-kinases and Src tyrosine kinases translate matrix and
      PDGF-initiated signals into cell motility. In experiments with cultured canine
      PASMCs, inhibition of PI 3-kinases with wortmannin (0.3 microM) and LY-294002 (50
      microM) and of Src kinase with PP1 (30 microM) did not decrease spontaneous
      (nonstimulated) or PDGF-stimulated (10 ng/ml) adhesion onto collagen. PI 3-kinase
      and Src kinase activities, however, were necessary for cell spreading: PP1
      inhibited cell spreading and Src Tyr-418 phosphorylation in a concentration
      dependent manner. Inhibition of PI 3-kinase and Src partially reduced cell
      migration, while at 10 and 30 microM, PP1 eliminated migration, likely due to
      inhibition of PDGF receptors. In conclusion, both PI 3-kinases and Src tyrosine
      kinases are components of pathways that mediate spreading and migration of
      cultured PASMCs on collagen.

PMID- 11443071
TI  - Contrasting effects of thiol-modulating agents on endothelial NO bioactivity.
AB  - The bioactivity of endothelium-derived nitric oxide (NO) is an important
      component of vascular homeostasis that is sensitive to intracellular redox
      status. Because glutathione (GSH) is a major determinant of intracellular redox
      state, we sought to define its role in modulating endothelial NO bioactivity. In
      porcine aortic endothelial cells (PAECs), we depleted intracellular GSH (>70%)
      using 1) buthionine-(S,R)-sulfoximine (BSO), which inhibits GSH synthesis; 2)
      diamide, which oxidizes thiols; or 3) 1-chloro-2,4-dinitrobenzene (CDNB), which
      putatively depletes GSH through glutathione S-transferase activity. Cellular GSH
      depletion with BSO had no effect on endothelial NO bioactivity measured as A
      23187-induced cGMP accumulation. In contrast, oxidation of intracellular thiols
      with diamide inhibited both A-23187-induced cGMP accumulation and the cGMP
      response to exogenous NO. Diamide treatment of either PAECs, PAEC membrane
      fractions, or purified endothelial nitric oxide synthase (eNOS) resulted in
      significant inhibition (approximately 75%) of eNOS catalytic activity measured as
      L-[(3)H]arginine-to-L-[(3)H]citrulline conversion. This effect appeared related
      to oxidation of eNOS thiols as it was completely reversed by dithiothreitol.
      Glutathione depletion with CDNB inhibited A-23187-stimulated cGMP accumulation
      but not the cGMP response to exogenous NO. Rather, CDNB treatment impaired eNOS
      catalytic activity in intact PAECs, and this effect was reversed by excess NADPH
      in isolated purified eNOS assays. Consistent with these results, we found
      spectral evidence that CDNB reacts with NADPH and renders it inactive as a
      cofactor for either eNOS or glutathione reductase. Thus thiol-modulating agents
      exert pleiotropic effects on endothelial NO bioactivity, and these data may help
      to resolve a number of conflicting previous studies linking GSH status with
      endothelial cell NO bioactivity.

PMID- 11443072
TI  - Direct in situ reverse transcriptase-polymerase chain reaction.
AB  - In situ hybridization has been used for localization of specific nucleic acid
      sequences at the cellular level despite providing relatively low-detection
      sensitivity. In situ reverse transcriptase-polymerase chain reactions (RT-PCR)
      enhance sensitivity and thus enable localization of low-abundance mRNA in a cell.
      However, the available methods are fraught with problems of nonspecific
      amplifications as a result of mispriming and/or amplification from partially
      digested residual genomic DNA in tissue. Herein, we demonstrate that nonspecific
      background amplification can be eliminated by pretreatment of samples with
      restriction enzymes before DNase I digestion. Primers tagged with a far-red
      shifted fluorescent dye such as Cy5 in PCR reactions allow identification of
      target mRNA by fluorescence microscopy. These novel modifications lead to
      increased specificity and rapid in situ detection of cellular mRNA and thus may
      be used for pathological diagnosis.

PMID- 11443073
TI  - Transposition of IS1397 in the family Enterobacteriaceae and first
      characterization of ISKpn1, a new insertion sequence associated with Klebsiella
      pneumoniae palindromic units.
AB  - IS1397 and ISKpn1 are IS3 family members which are specifically inserted into the
      loop of palindromic units (PUs). IS1397 is shown to transpose into PUs with
      sequences close or identical to the Escherichia coli consensus, even in other
      enterobacteria (Salmonella enterica serovar Typhimurium, Klebsiella pneumoniae,
      and Klebsiella oxytoca). Moreover, we show that homologous intergenic regions
      containing PUs constitute IS1397 transpositional hot spots, despite bacterial
      interspersed mosaic element structures that differ among the three species.
      ISKpn1, described here for the first time, is specific for PUs from K.
      pneumoniae, in which we discovered it. A sequence comparison between the two
      insertion sequences allowed us to define a motif possibly accounting for their
      specificity.

PMID- 11443074
TI  - Complex regulation of the organic hydroperoxide resistance gene (ohr) from
      Xanthomonas involves OhrR, a novel organic peroxide-inducible negative regulator,
      and posttranscriptional modifications.
AB  - Analysis of the sequence immediate upstream of ohr revealed an open reading
      frame, designated ohrR, with the potential to encode a 17-kDa peptide with
      moderate amino acid sequence homology to the MarR family of negative regulators
      of gene expression. ohrR was transcribed as bicistronic mRNA with ohr, while ohr
      mRNA was found to be 95% monocistronic and 5% bicistronic with ohrR. Expression
      of both genes was induced by tert-butyl hydroperoxide (tBOOH) treatment. High
      level expression of ohrR negatively regulated ohr expression. This repression
      could be overcome by tBOOH treatment. In vivo promoter analysis showed that the
      ohrR promoter (P1) has organic peroxide-inducible, strong activity, while the ohr
      promoter (P2) has constitutive, weak activity. Only P1 is autoregulated by OhrR.
      ohr primer extension results revealed three major primer extension products
      corresponding to the 5' ends of ohr mRNA, and their levels were strongly induced
      by tBOOH treatment. Sequence analysis of regions upstream of these sites showed
      no typical Xanthomonas promoter. Instead, the regions can form a stem-loop
      secondary structure with the 5' ends of ohr mRNA located in the loop section. The
      secondary structure resembles the structure recognized and processed by RNase III
      enzyme. These findings suggest that the P1 promoter is responsible for tBOOH
      induced expression of the ohrR-ohr operon. The bicistronic mRNA is then processed
      by RNase III-like enzymes to give high levels of ohr mRNA, while ohrR mRNA is
      rapidly degraded.

PMID- 11443075
TI  - Molecular characterization of Desulfovibrio gigas neelaredoxin, a protein
      involved in oxygen detoxification in anaerobes.
AB  - Desulfovibrio gigas neelaredoxin is an iron-containing protein of 15 kDa, having
      a single iron site with a His(4)Cys coordination. Neelaredoxins and homologous
      proteins are widespread in anaerobic prokaryotes and have superoxide-scavenging
      activity. To further understand its role in anaerobes, its genomic organization
      and expression in D. gigas were studied and its ability to complement Escherichia
      coli superoxide dismutase deletion mutant was assessed. In D. gigas, neelaredoxin
      is transcribed as a monocistronic mRNA of 500 bases as revealed by Northern
      analysis. Putative promoter elements resembling sigma(70) recognition sequences
      were identified. Neelaredoxin is abundantly and constitutively expressed, and its
      expression is not further induced during treatment with O(2) or H(2)O(2). The
      neelaredoxin gene was cloned by PCR and expressed in E. coli, and the protein was
      purified to homogeneity. The recombinant neelaredoxin has spectroscopic
      properties identical to those observed for the native one. Mutations of Cys-115,
      one of the iron ligands, show that this ligand is essential for the activity of
      neelaredoxin. In an attempt to elucidate the function of neelaredoxin within the
      cell, it was expressed in an E. coli mutant deficient in cytoplasmic superoxide
      dismutases (sodA sodB). Neelaredoxin suppresses the deleterious effects produced
      by superoxide, indicating that it is involved in oxygen detoxification in the
      anaerobe D. gigas.

PMID- 11443076
TI  - Methionine regeneration and aspartate aminotransferase in parasitic protozoa.
AB  - Aspartate aminotransferases have been cloned and expressed from Crithidia
      fasciculata, Trypanosoma brucei brucei, Giardia intestinalis, and Plasmodium
      falciparum and have been found to play a role in the final step of methionine
      regeneration from methylthioadenosine. All five enzymes contain sequence motifs
      consistent with membership in the Ia subfamily of aminotransferases; the
      crithidial and giardial enzymes and one trypanosomal enzyme were identified as
      cytoplasmic aspartate aminotransferases, and the second trypanosomal enzyme was
      identified as a mitochondrial aspartate aminotransferase. The plasmodial enzyme
      contained unique sequence substitutions and appears to be highly divergent from
      the existing members of the Ia subfamily. In addition, the P. falciparum enzyme
      is the first aminotransferase found to lack the invariant residue G197 (P. K.
      Mehta, T. I. Hale, and P. Christen, Eur. J. Biochem. 214:549-561, 1993), a
      feature shared by sequences discovered in P. vivax and P. berghei. All five
      enzymes were able to catalyze aspartate-ketoglutarate, tyrosine-ketoglutarate,
      and amino acid-ketomethiobutyrate aminotransfer reactions. In the latter,
      glutamate, phenylalanine, tyrosine, tryptophan, and histidine were all found to
      be effective amino donors. The crithidial and trypanosomal cytosolic
      aminotransferases were also able to catalyze alanine-ketoglutarate and glutamine
      ketoglutarate aminotransfer reactions and, in common with the giardial
      aminotransferase, were able to catalyze the leucine-ketomethiobutyrate
      aminotransfer reaction. In all cases, the kinetic constants were broadly similar,
      with the exception of that of the plasmodial enzyme, which catalyzed the
      transamination of ketomethiobutyrate significantly more slowly than aspartate
      ketoglutarate aminotransfer. This result obtained with the recombinant P.
      falciparum aminotransferase parallels the results seen for total
      ketomethiobutyrate transamination in malarial homogenates; activity in the latter
      was much lower than that in homogenates from other organisms. Total
      ketomethiobutyrate transamination in Trichomonas vaginalis and G. intestinalis
      homogenates was extensive and involved lysine-ketomethiobutyrate enzyme activity
      in addition to the aspartate aminotransferase activity. The methionine production
      in these two species could be inhibited by the amino-oxy compounds canaline and
      carboxymethoxylamine. Canaline was also found to be an uncompetitive inhibitor of
      the plasmodial aspartate aminotransferase, with a K(i) of 27 microm.

PMID- 11443077
TI  - Novel topology of BfpE, a cytoplasmic membrane protein required for type IV
      fimbrial biogenesis in enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) produces the bundle-forming pilus (BFP),
      a type IV fimbria that has been implicated in virulence, autoaggregation, and
      localized adherence to epithelial cells. The bfpE gene is one of a cluster of bfp
      genes previously shown to encode functions that direct BFP biosynthesis. Here, we
      show that an EPEC strain carrying a nonpolar mutation in bfpE fails to
      autoaggregate, adhere to HEp-2 cells, or form BFP, thereby demonstrating that
      BfpE is required for BFP biogenesis. BfpE is a cytoplasmic membrane protein of
      the GspF family. To determine the membrane topology of BfpE, we fused bfpE
      derivatives containing 3' truncations and/or internal deletions to alkaline
      phosphatase and/or beta-galactosidase reporter genes, whose products are active
      only when localized to the periplasm or cytoplasm, respectively. In addition, we
      constructed BfpE sandwich fusions using a dual alkaline phosphatase/beta
      galactosidase reporter cassette and analyzed BfpE deletion derivatives by sucrose
      density flotation gradient fractionation. The data from these analyses support a
      topology in which BfpE contains four hydrophobic transmembrane (TM) segments, a
      large cytoplasmic segment at its N terminus, and a large periplasmic segment near
      its C terminus. This topology is dramatically different from that of OutF,
      another member of the GspF family, which has three TM segments and is
      predominantly cytoplasmic. These findings provide a structural basis for
      predicting protein-protein interactions required for assembly of the BFP
      biogenesis machinery.

PMID- 11443078
TI  - The type IV fimbrial subunit gene (fimA) of Dichelobacter nodosus is essential
      for virulence, protease secretion, and natural competence.
AB  - Dichelobacter nodosus is the essential causative agent of footrot in sheep. The
      major D. nodosus-encoded virulence factors that have been implicated in the
      disease are type IV fimbriae and extracellular proteases. To examine the role of
      the fimbriae in virulence, allelic exchange was used to insertionally inactivate
      the fimA gene, which encodes the fimbrial subunit protein, from the virulent type
      G D. nodosus strain VCS1703A. Detailed analysis of two independently derived fimA
      mutants revealed that they no longer produced the fimbrial subunit protein or
      intact fimbriae and did not exhibit twitching motility. In addition, these
      mutants were no longer capable of undergoing natural transformation and did not
      secrete wild-type levels of extracellular proteases. These effects were not due
      to polar effects on the downstream fimB gene because insertionally inactivated
      fimB mutants were not defective in any of these phenotypic tests. Virulence
      testing of the mutants in a sheep pen trial conducted under controlled
      environmental conditions showed that the fimA mutants were avirulent, providing
      evidence that the fimA gene is an essential D. nodosus virulence gene. These
      studies represent the first time that molecular genetics has been used to
      determine the role of virulence genes in this slow growing anaerobic bacterium.

PMID- 11443079
TI  - Identification of some DNA damage-inducible genes of Mycobacterium tuberculosis:
      apparent lack of correlation with LexA binding.
AB  - The repair of DNA damage is expected to be particularly important to
      intracellular pathogens such as Mycobacterium tuberculosis, and so it is of
      interest to examine the response of M. tuberculosis to DNA damage. The expression
      of recA, a key component in DNA repair and recombination, is induced by DNA
      damage in M. tuberculosis. In this study, we have analyzed the expression
      following DNA damage in M. tuberculosis of a number of other genes which are DNA
      damage inducible in Escherichia coli. While many of these genes were also induced
      by DNA damage in M. tuberculosis, some were not. In addition, one gene (ruvC)
      which is not induced by DNA damage in E. coli was induced in M. tuberculosis, a
      result likely linked to its different transcriptional arrangement in M.
      tuberculosis. We also searched the sequences upstream of the genes being studied
      for the mycobacterial SOS box (the binding site for LexA) and assessed LexA
      binding to potential sites identified. LexA is the repressor protein responsible
      for regulating expression of these SOS genes in E. coli. However, two of the
      genes which were DNA damage inducible in M. tuberculosis did not have
      identifiable sites to which LexA bound. The absence of binding sites for LexA
      upstream of these genes was confirmed by analysis of LexA binding to overlapping
      DNA fragments covering a region from 500 bp upstream of the coding sequence to
      100 bp within it. Therefore, it appears most likely that an alternative mechanism
      of gene regulation in response to DNA damage exists in M. tuberculosis.

PMID- 11443080
TI  - Isolation and characterization of a soluble NADPH-dependent Fe(III) reductase
      from Geobacter sulfurreducens.
AB  - NADPH is an intermediate in the oxidation of organic compounds coupled to Fe(III)
      reduction in Geobacter species, but Fe(III) reduction with NADPH as the electron
      donor has not been studied in these organisms. Crude extracts of Geobacter
      sulfurreducens catalyzed the NADPH-dependent reduction of Fe(III)
      nitrilotriacetic acid (NTA). The responsible enzyme, which was recovered in the
      soluble protein fraction, was purified to apparent homogeneity in a four-step
      procedure. Its specific activity for Fe(III) reduction was 65 micromol. min(-1).
      mg(-1). The soluble Fe(III) reductase was specific for NADPH and did not utilize
      NADH as an electron donor. Although the enzyme reduced several forms of Fe(III),
      Fe(III)-NTA was the preferred electron acceptor. The protein possessed methyl
      viologen:NADP(+) oxidoreductase activity and catalyzed the reduction of NADP(+)
      with reduced methyl viologen as electron donor at a rate of 385 U/mg. The enzyme
      consisted of two subunits with molecular masses of 87 and 78 kDa and had a native
      molecular mass of 320 kDa, as determined by gel filtration. The purified enzyme
      contained 28.9 mol of Fe, 17.4 mol of acid-labile sulfur, and 0.7 mol of flavin
      adenine dinucleotide per mol of protein. The genes encoding the two subunits were
      identified in the complete sequence of the G. sulfurreducens genome from the N
      terminal amino acid sequences derived from the subunits of the purified protein.
      The sequences of the two subunits had about 30% amino acid identity to the
      respective subunits of the formate dehydrogenase from Moorella thermoacetica, but
      the soluble Fe(III) reductase did not possess formate dehydrogenase activity.
      This soluble Fe(III) reductase differs significantly from previously
      characterized dissimilatory and assimilatory Fe(III) reductases in its molecular
      composition and cofactor content.

PMID- 11443081
TI  - Eukaryotic translation initiation factor 4E-dependent translation is not
      essential for survival of starved yeast cells.
AB  - The eukaryotic translation initiation factor 4E (eIF4E) interacts with the mRNA
      5' cap structure (m(7)GpppX) and is essential for the appropriate translation of
      the vast majority of eukaryotic mRNAs. Most studies of the yeast Saccharomyces
      cerevisiae CDC33 gene product, eIF4E, have been carried out with logarithmically
      growing cells, and little is known about its role in starved, nonproliferating
      cells that enter the stationary phase (SP). It has previously been found that the
      rate of translation in SP cells is more than 2 orders of magnitude lower than it
      is in dividing yeast cells. Here we show that this low rate of translation is
      essential for maintaining the viability of starved yeast cells that enter SP.
      Specifically, starved cells whose eIF4A is inactive or treated with cycloheximide
      rapidly lose viability. Moreover, after heat inactivation of the cdc33
      temperature-sensitive product, the synthesis of most proteins is abolished and
      only a small group of proteins is still produced. Unexpectedly, starved cdc33
      mutant cells whose eIF4E is inactive and which therefore fail to synthesize the
      bulk of their proteins remain viable for long periods of time, indistinguishable
      from their isogenic wild-type counterparts. Taken together, our results indicate
      that eIF4E-independent translation is necessary and sufficient for survival of
      yeast cells during long periods of starvation.

PMID- 11443082
TI  - Identification, cloning, expression, and characterization of the extracellular
      acarbose-modifying glycosyltransferase, AcbD, from Actinoplanes sp. strain SE50.
AB  - An extracellular enzyme activity in the culture supernatant of the acarbose
      producer Actinoplanes sp. strain SE50 catalyzes the transfer of the acarviosyl
      moiety of acarbose to malto-oligosaccharides. This acarviosyl transferase (ATase)
      is encoded by a gene, acbD, in the putative biosynthetic gene cluster for the
      alpha-glucosidase inhibitor acarbose. The acbD gene was cloned and heterologously
      produced in Streptomyces lividans TK23. The recombinant protein was analyzed by
      enzyme assays. The AcbD protein (724 amino acids) displays all of the features of
      extracellular alpha-glucosidases and/or transglycosylases of the alpha-amylase
      family and exhibits the highest similarities to several cyclodextrin
      glucanotransferases (CGTases). However, AcbD had neither alpha-amylase nor CGTase
      activity. The AcbD protein was purified to homogeneity, and it was identified by
      partial protein sequencing of tryptic peptides. AcbD had an apparent molecular
      mass of 76 kDa and an isoelectric point of 5.0 and required Ca(2+) ions for
      activity. The enzyme displayed maximal activity at 30 degrees C and between pH
      6.2 and 6.9. The K(m) values of the ATase for acarbose (donor substrate) and
      maltose (acceptor substrate) are 0.65 and 0.96 mM, respectively. A wide range of
      additional donor and acceptor substrates were determined for the enzyme.
      Acceptors revealed a structural requirement for glucose-analogous structures
      conserving only the overall stereochemistry, except for the anomeric C atom, and
      the hydroxyl groups at positions 2, 3, and 4 of D-glucose. We discuss here the
      function of the enzyme in the extracellular formation of the series of acarbose
      homologous compounds produced by Actinoplanes sp. strain SE50.

PMID- 11443083
TI  - Properties of a revertant of Escherichia coli viable in the presence of
      spermidine accumulation: increase in L-glycerol 3-phosphate.
AB  - Escherichia coli CAG2242 cells are deficient in the speG gene encoding spermidine
      acetyltransferase. When these cells were cultured in the presence of 0.5 to 4 mM
      spermidine, their viability was greatly decreased through the inhibition of
      protein synthesis by overaccumulation of spermidine. When the cells were cultured
      with a high concentration of spermidine (4 mM), a revertant strain was obtained.
      We found that a 55-kDa protein, glycerol kinase, was overexpressed in the
      revertant and that synthesis of a ribosome modulation factor and the RNA
      polymerase sigma(38) subunit, factors important for cell viability, was increased
      in the revertant. Levels of L-glycerol 3-phosphate also increased in the
      revertant. Transformation of glpFK, which encodes a glycerol diffusion
      facilitator (glpF) and glycerol kinase (glpK), to E. coli CAG2242 partially
      prevented the cell death caused by accumulation of spermidine. It was also found
      that L-glycerol 3-phosphate inhibited spermidine binding to ribosomes and
      attenuated the inhibition of protein synthesis caused by high concentrations of
      spermidine. These results indicate that L-glycerol 3-phosphate reduces the
      binding of excess amounts of spermidine to ribosomes so that protein synthesis is
      recovered.

PMID- 11443084
TI  - Novel genes of the sox gene cluster, mutagenesis of the flavoprotein SoxF, and
      evidence for a general sulfur-oxidizing system in Paracoccus pantotrophus GB17.
AB  - The novel genes soxFGH were identified, completing the sox gene cluster of
      Paracoccus pantotrophus coding for enzymes involved in lithotrophic sulfur
      oxidation. The periplasmic SoxF, SoxG, and SoxH proteins were induced by
      thiosulfate and purified to homogeneity from the soluble fraction. soxF coded for
      a protein of 420 amino acids with a signal peptide containing a twin-arginine
      motif. SoxF was 37% identical to the flavoprotein FccB of flavocytochrome c
      sulfide dehydrogenase of Allochromatium vinosum. The mature SoxF (42,832 Da)
      contained 0.74 mol of flavin adenine dinucleotide per mol. soxG coded for a novel
      protein of 303 amino acids with a signal peptide containing a twin-arginine
      motif. The mature SoxG (29,657 Da) contained two zinc binding motifs and 0.90
      atom of zinc per subunit of the homodimer. soxH coded for a periplasmic protein
      of 317 amino acids with a double-arginine signal peptide. The mature SoxH (32,317
      Da) contained two metal binding motifs and 0.29 atom of zinc and 0.20 atom of
      copper per subunit of the homodimer. SoxXA, SoxYZ, SoxB, and SoxCD (C. G.
      Friedrich, A. Quentmeier, F. Bardischewsky, D. Rother, R. Kraft, S. Kostka, and
      H. Prinz, J. Bacteriol. 182:4476-4487, 2000) reconstitute a system able to
      perform thiosulfate-, sulfite-, sulfur-, and hydrogen sulfide-dependent
      cytochrome c reduction, and this system is the first described for oxidizing
      different inorganic sulfur compounds. SoxF slightly inhibited the rate of
      hydrogen sulfide oxidation but not the rate of sulfite or thiosulfate oxidation.
      From use of a homogenote mutant with an in-frame deletion in soxF and
      complementation analysis, it was evident that the soxFGH gene products were not
      required for lithotrophic growth with thiosulfate.

PMID- 11443085
TI  - Respiration capacity of the fermenting bacterium Lactococcus lactis and its
      positive effects on growth and survival.
AB  - Oxygen is a major determinant of both survival and mortality of aerobic
      organisms. For the facultative anaerobe Lactococcus lactis, oxygen has negative
      effects on both growth and survival. We show here that oxygen can be beneficial
      to L. lactis if heme is present during aerated growth. The growth period is
      extended and long-term survival is markedly improved compared to results obtained
      under the usual fermentation conditions. We considered that improved growth and
      survival could be due to the capacity of L. lactis to undergo respiration. To
      test this idea, we confirmed that the metabolic behavior of lactococci in the
      presence of oxygen and hemin is consistent with respiration and is most
      pronounced late in growth. We then used a genetic approach to show the following.
      (i) The cydA gene, encoding cytochrome d oxidase, is required for respiration and
      plays a direct role in oxygen utilization. cydA expression is induced late in
      growth under respiration conditions. (ii) The hemZ gene, encoding ferrochelatase,
      which converts protoporphyrin IX to heme, is needed for respiration if the
      precursor, rather than the final heme product, is present in the medium.
      Surprisingly, survival improved by respiration is observed in a superoxide
      dismutase-deficient strain, a result which emphasizes the physiological
      differences between fermenting and respiring lactococci. These studies confirm
      respiratory metabolism in L. lactis and suggest that this organism may be better
      adapted to respiration than to traditional fermentative metabolism.

PMID- 11443086
TI  - Genome size determination and coding capacity of Sodalis glossinidius, an enteric
      symbiont of tsetse flies, as revealed by hybridization to Escherichia coli gene
      arrays.
AB  - Recent molecular characterization of various microbial genomes has revealed
      differences in genome size and coding capacity between obligate symbionts and
      intracellular pathogens versus free-living organisms. Multiple symbiotic
      microorganisms have evolved with tsetse fly, the vector of African trypanosomes,
      over long evolutionary times. Although these symbionts are indispensable for
      tsetse fecundity, the biochemical and molecular basis of their functional
      significance is unknown. Here, we report on the genomic aspects of the secondary
      symbiont Sodalis glossinidius. The genome size of Sodalis is approximately 2 Mb.
      Its DNA is subject to extensive methylation and based on some of its conserved
      gene sequences has an A+T content of only 45%, compared to the typically AT-rich
      genomes of endosymbionts. Sodalis also harbors an extrachromosomal plasmid about
      134 kb in size. We used a novel approach to gain insight into Sodalis genomic
      contents, i.e., hybridizing its DNA to macroarrays developed for Escherichia
      coli, a closely related enteric bacterium. In this analysis we detected 1,800
      orthologous genes, corresponding to about 85% of the Sodalis genome. The Sodalis
      genome has apparently retained its genes for DNA replication, transcription,
      translation, transport, and the biosynthesis of amino acids, nucleic acids,
      vitamins, and cofactors. However, many genes involved in energy metabolism and
      carbon compound assimilation are apparently missing, which may indicate an
      adaptation to the energy sources available in the only nutrient of the tsetse
      host, blood. We present gene arrays as a rapid tool for comparative genomics in
      the absence of whole genome sequence to advance our understanding of closely
      related bacteria.

PMID- 11443087
TI  - Identification of the domains of UreR, an AraC-like transcriptional regulator of
      the urease gene cluster in Proteus mirabilis.
AB  - Proteus mirabilis urease catalyzes the hydrolysis of urea to CO(2) and NH(3),
      resulting in urinary stone formation in individuals with complicated urinary
      tract infections. UreR, a member of the AraC family, activates transcription of
      the genes encoding urease enzyme subunits and accessory proteins, ureDABCEFG, as
      well as its own transcription in the presence of urea. Based on sequence homology
      with AraC, we hypothesized that UreR contains both a dimerization domain and a
      DNA-binding domain. A translational fusion of the leucine zipper dimerization
      domain (amino acids 302 to 350) of C/EBP and the C-terminal half of UreR (amino
      acids 164 to 293) activated transcription from the ureD promoter (p(ureD)) and
      bound to a 60-bp fragment containing p(ureD), as analyzed by gel shift. These
      results were consistent with the DNA-binding specificity residing in the C
      terminal half of UreR and dimerization being required for activity. To localize
      the dimerization domain of UreR, a translational fusion of the DNA-binding domain
      of the LexA repressor (amino acids 1 to 87) and the N-terminal half of UreR
      (amino acids 1 to 182) was constructed and found to repress transcription from
      p(sulA)-lacZ (sulA is repressed by LexA) and bind to the sulA operator site, as
      analyzed by gel shift. Since LexA binds this site only as a dimer, the UreR(1
      182)-LexA(1-87) fusion also must dimerize to bind p(sulA). Indeed, purified UreR
      Myc-His eluted from a gel filtration column as a dimer. Therefore, we conclude
      that the dimerization domain of UreR is located within the N-terminal half of
      UreR. UreR contains three leucines that mimic the leucines that contribute to
      dimerization of AraC. Mutagenesis of Leu147, Leu148, or L158 alone did not
      significantly affect UreR function. In contrast, mutagenesis of both Leu147 and
      Leu148 or all three Leu residues resulted in a 85 or 94% decrease, respectively,
      in UreR function in the presence of urea (P < 0.001). On the contrary, His102 and
      His175 mutations of UreR resulted in constitutive induction in the absence of
      urea. We conclude that a dimerization domain resides in the N-terminal half of
      the polypeptide, that Leu residues may contribute to this function, and that
      sequences within the C-terminal half of UreR are responsible for DNA binding to
      the urease promoter regions. Selected His residues also contribute significantly
      to UreR function.

PMID- 11443088
TI  - Isolation and characterization of anaerobic ethylbenzene dehydrogenase, a novel
      Mo-Fe-S enzyme.
AB  - The first step in anaerobic ethylbenzene mineralization in denitrifying Azoarcus
      sp. strain EB1 is the oxidation of ethylbenzene to (S)-(-)-1-phenylethanol.
      Ethylbenzene dehydrogenase, which catalyzes this reaction, is a unique enzyme in
      that it mediates the stereoselective hydroxylation of an aromatic hydrocarbon in
      the absence of molecular oxygen. We purified ethylbenzene dehydrogenase to
      apparent homogeneity and showed that the enzyme is a heterotrimer
      (alphabetagamma) with subunit masses of 100 kDa (alpha), 35 kDa (beta), and 25
      kDa (gamma). Purified ethylbenzene dehydrogenase contains approximately 0.5 mol
      of molybdenum, 16 mol of iron, and 15 mol of acid-labile sulfur per mol of
      holoenzyme, as well as a molydopterin cofactor. In addition to ethylbenzene,
      purified ethylbenzene dehydrogenase was found to oxidize 4-fluoro-ethylbenzene
      and the nonaromatic hydrocarbons 3-methyl-2-pentene and ethylidenecyclohexane.
      Sequencing of the encoding genes revealed that ebdA encodes the alpha subunit, a
      974-amino-acid polypeptide containing a molybdopterin-binding domain. The ebdB
      gene encodes the beta subunit, a 352-amino-acid polypeptide with several 4Fe-4S
      binding domains. The ebdC gene encodes the gamma subunit, a 214-amino-acid
      polypeptide that is a potential membrane anchor subunit. Sequence analysis and
      biochemical data suggest that ethylbenzene dehydrogenase is a novel member of the
      dimethyl sulfoxide reductase family of molybdopterin-containing enzymes.

PMID- 11443089
TI  - Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic
      microcin J25.
AB  - Escherichia coli microcin J25 (MccJ25) is a plasmid-encoded, cyclic peptide
      antibiotic consisting of 21 unmodified amino acid residues. It is primarily
      active on gram-negative bacteria related to the producer strain, inducing cell
      filamentation in an SOS-independent way. A mutation causing resistance to MccJ25
      was isolated. Genetic analysis indicated that it resided in the rpoC gene,
      encoding the beta' subunit of RNA polymerase, at 90 min on the E. coli genetic
      map. The mutation was genetically crossed on to a plasmid containing the wild
      type rpoC gene. The presence of the recombinant plasmid conferred complete
      resistance to otherwise sensitive strains. Nucleotide sequencing of the plasmid
      borne, mutant rpoC gene revealed a ACC (Thr)-to-ATC (Ile) change at codon 931,
      within homology block G, an evolutionarily conserved region in the large subunits
      of all RNA polymerases. MccJ25 decreased RNA synthesis both in vivo and in vitro.
      These results point to the RNA polymerase as the target of microcin action. We
      favor the possibility that the filamentous phenotype induced by MccJ25 results
      from impaired transcription of genes coding for cell division proteins. As far as
      we know, MccJ25 is the first peptide antibiotic shown to affect RNA polymerase.

PMID- 11443090
TI  - Mechanism of chloride elimination from 3-chloro- and 2,4-dichloro-cis,cis
      muconate: new insight obtained from analysis of muconate cycloisomerase variant
      CatB-K169A.
AB  - Chloromuconate cycloisomerases of bacteria utilizing chloroaromatic compounds are
      known to convert 3-chloro-cis,cis-muconate to cis-dienelactone (cis-4
      carboxymethylenebut-2-en-4-olide), while usual muconate cycloisomerases transform
      the same substrate to the bacteriotoxic protoanemonin. Formation of protoanemonin
      requires that the cycloisomerization of 3-chloro-cis,cis-muconate to 4
      chloromuconolactone is completed by protonation of the exocyclic carbon of the
      presumed enol/enolate intermediate before chloride elimination and
      decarboxylation take place to yield the final product. The formation of cis
      dienelactone, in contrast, could occur either by dehydrohalogenation of 4
      chloromuconolactone or, more directly, by chloride elimination from the
      enol/enolate intermediate. To reach a better understanding of the mechanisms of
      chloride elimination, the proton-donating Lys169 of Pseudomonas putida muconate
      cycloisomerase was changed to alanine. As expected, substrates requiring
      protonation, such as cis,cis-muconate as well as 2- and 3-methyl-, 3-fluoro-, and
      2-chloro-cis,cis-muconate, were not converted at a significant rate by the K169A
      variant. However, the variant was still active with 3-chloro- and 2,4-dichloro
      cis,cis-muconate. Interestingly, cis-dienelactone and 2-chloro-cis-dienelactone
      were formed as products, whereas the wild-type enzyme forms protoanemonin and the
      not previously isolated 2-chloroprotoanemonin, respectively. Thus, the
      chloromuconate cycloisomerases may avoid (chloro-)protoanemonin formation by
      increasing the rate of chloride abstraction from the enol/enolate intermediate
      compared to that of proton addition to it.

PMID- 11443091
TI  - DNA microarray-mediated transcriptional profiling of the Escherichia coli
      response to hydrogen peroxide.
AB  - The genome-wide transcription profile of Escherichia coli cells treated with
      hydrogen peroxide was examined with a DNA microarray composed of 4,169 E. coli
      open reading frames. By measuring gene expression in isogenic wild-type and oxyR
      deletion strains, we confirmed that the peroxide response regulator OxyR
      activates most of the highly hydrogen peroxide-inducible genes. The DNA
      microarray measurements allowed the identification of several new OxyR-activated
      genes, including the hemH heme biosynthetic gene; the six-gene suf operon, which
      may participate in Fe-S cluster assembly or repair; and four genes of unknown
      function. We also identified several genes, including uxuA, encoding mannonate
      hydrolase, whose expression might be repressed by OxyR, since their expression
      was elevated in the DeltaoxyR mutant strain. In addition, the induction of some
      genes was found to be OxyR independent, indicating the existence of other
      peroxide sensors and regulators in E. coli. For example, the isc operon, which
      specifies Fe-S cluster formation and repair activities, was induced by hydrogen
      peroxide in strains lacking either OxyR or the superoxide response regulators
      SoxRS. These results expand our understanding of the oxidative stress response
      and raise interesting questions regarding the nature of other regulators that
      modulate gene expression in response to hydrogen peroxide.

PMID- 11443092
TI  - Computation-directed identification of OxyR DNA binding sites in Escherichia
      coli.
AB  - A computational search was carried out to identify additional targets for the
      Escherichia coli OxyR transcription factor. This approach predicted OxyR binding
      sites upstream of dsbG, encoding a periplasmic disulfide bond chaperone
      isomerase; upstream of fhuF, encoding a protein required for iron uptake; and
      within yfdI. DNase I footprinting assays confirmed that oxidized OxyR bound to
      the predicted site centered 54 bp upstream of the dsbG gene and 238 bp upstream
      of a known OxyR binding site in the promoter region of the divergently
      transcribed ahpC gene. Although the new binding site was near dsbG, Northern
      blotting and primer extension assays showed that OxyR binding to the dsbG
      proximal site led to the induction of a second ahpCF transcript, while OxyR
      binding to the ahpCF-proximal site leads to the induction of both dsbG and ahpC
      transcripts. Oxidized OxyR binding to the predicted site centered 40 bp upstream
      of the fhuF gene was confirmed by DNase I footprinting, but these assays further
      revealed a second higher-affinity site in the fhuF promoter. Interestingly, the
      two OxyR sites in the fhuF promoter overlapped with two regions bound by the Fur
      repressor. Expression analysis revealed that fhuF was repressed by hydrogen
      peroxide in an OxyR-dependent manner. Finally, DNase I footprinting experiments
      showed OxyR binding to the site predicted to be within the coding sequence of
      yfdI. These results demonstrate the versatile modes of regulation by OxyR and
      illustrate the need to learn more about the ensembles of binding sites and
      transcripts in the E. coli genome.

PMID- 11443093
TI  - Cytotoxic and genotoxic consequences of heat stress are dependent on the presence
      of oxygen in Saccharomyces cerevisiae.
AB  - Lethal heat stress generates oxidative stress in Saccharomyces cerevisiae, and
      anaerobic cells are several orders of magnitude more resistant than aerobic cells
      to a 50 degrees C heat shock. Here we characterize the oxidative effects of this
      heat stress. The thermoprotective effect in anaerobic cells was not due to
      expression of HSP104 or any other heat shock gene, raising the possibility that
      the toxicity of lethal heat shock is due mainly to oxidative stress. Aerobic but
      not anaerobic heat stress caused elevated frequencies of forward mutations and
      interchromosomal DNA recombination. Oxidative DNA repair glycosylase-deficient
      strains under aerobic conditions showed a powerful induction of forward mutation
      frequencies compared to wild-type cells, which was completely abolished under
      anaerobiosis. We also investigated potential causes for this oxygen-dependent
      heat shock-induced genetic instability. Levels of sulfhydryl groups, dominated
      mainly by the high levels of the antioxidant glutathione (reduced form) and
      levels of vitamin E, decreased after aerobic heat stress but not after anaerobic
      heat stress. Aerobic heat stress also led to an increase in mitochondrial
      membrane disruption of several hundredfold, which was 100-fold reduced under
      anaerobic conditions.

PMID- 11443094
TI  - Roles of LcrG and LcrV during type III targeting of effector Yops by Yersinia
      enterocolitica.
AB  - Yersinia enterocolitica target effector Yop proteins into the cytosol of
      eukaryotic cells by a mechanism requiring the type III machinery. LcrG and LcrV
      have been suggested to fulfill essential functions during the type III targeting
      of effector Yops. It is reported here that knockout mutations of lcrG caused
      mutant yersiniae to prematurely secrete Yops into the extracellular medium
      without abolishing the type III targeting mechanism (Los phenotype [loss of type
      III targeting specificity]). Knockout mutations in lcrV reduced type III
      targeting of mutant yersiniae but did not promote secretion into the
      extracellular medium (Not [no type III targeting]). However, knockout mutations
      in both genes caused DeltalcrGV yersiniae to display a Los phenotype similar to
      that of strains carrying knockout mutations in lcrG alone. LcrG binding to LcrV
      resulted in the formation of soluble LcrGV complexes in the bacterial cytoplasm.
      Membrane-associated, bacterial-surface-displayed or -secreted LcrG could not be
      detected. Most of LcrV was located in the bacterial cytoplasm; however, small
      amounts were secreted into the extracellular medium. These data support a model
      whereby LcrG may act as a negative regulator of type III targeting in the
      bacterial cytoplasm, an activity that is modulated by LcrG binding to LcrV. No
      support could be gathered for the hypothesis whereby LcrG and LcrV may act as a
      bacterial surface receptor for host cells, allowing effector Yop translocation
      across the eukaryotic plasma membrane.

PMID- 11443095
TI  - Competence repression under oxygen limitation through the two-component MicAB
      signal-transducing system in Streptococcus pneumoniae and involvement of the PAS
      domain of MicB.
AB  - In Streptococcus pneumoniae, a fermentative aerotolerant and catalase-deficient
      human pathogen, oxidases with molecular oxygen as substrate are important for
      virulence and for competence. The signal-transducing two-component systems CiaRH
      and ComDE mediate the response to oxygen, culminating in competence. In this work
      we show that the two-component MicAB system, whose MicB kinase carries a PAS
      domain, is also involved in competence repression under oxygen limitation.
      Autophosphorylation of recombinant MicB and phosphotransfer to recombinant MicA
      have been demonstrated. Mutational analysis and in vitro assays showed that the C
      terminal part of the protein and residue L100 in the N-terminal cap of its PAS
      domain are both crucial for autokinase activity in vitro. Although no insertion
      mutation in micA was obtained, expression of the mutated allele micA59DA did not
      change bacterial growth and overcame competence repression under microaerobiosis.
      This was related to a strong instability of MicA59DA-PO(4) in vitro. Thus,
      mutations which either reduced the stability of MicA-PO(4) or abolished kinase
      activity in MicB were related to competence derepression under microaerobiosis,
      suggesting that MicA-PO(4) is involved in competence repression when oxygen
      becomes limiting. The micAB genes are flanked by mutY and orfC. MutY is an
      adenine glycosylase involved in the repair of oxidized pyrimidines. OrfC shows
      the features of a metal binding protein. We did not obtain insertion mutation in
      orfC, suggesting its requirement for growth. It is proposed that MicAB, with its
      PAS motif, may belong to a set of functions important in the protection of the
      cell against oxidative stress, including the control of competence.

PMID- 11443096
TI  - Regulation of Staphylococcus aureus type 5 and type 8 capsular polysaccharides by
      CO(2).
AB  - Staphylococcus aureus expression of capsular polysaccharide type 5 (CP5) has been
      shown to be downregulated by CO(2). Here we show that CO(2) reduces CP5
      expression at the transcriptional level and that CO(2) regulates CP8 expression
      depending on the genetic background of the strains. Growth in the presence of air
      supplemented with 5% CO(2) caused a significant decrease in CP8 expression in
      four S. aureus strains, a marginal effect in four strains, and higher CP8
      expression in strain Becker. Absolute CP8 expression in the nine S. aureus
      strains differed largely from strain to strain. Four groups of strains were
      established due to sequence variations in the promoter region of cap5 and cap8.
      To test whether these sequence variations are responsible for the different
      responses to CO(2), promoter regions from selected strains were fused to the
      reporter gene xylE in pLC4, and the plasmids were electrotransformed into strains
      Becker and Newman. XylE activity was negatively regulated by CO(2) in all
      derivatives of strain Newman and was always positively regulated by CO(2) in all
      derivatives of strain Becker. Differences in promoter sequences did not influence
      the pattern of CP8 expression. Therefore, the genetic background of the strains
      rather than differences in the promoter sequence determines the CO(2) response.
      trans-acting regulatory molecules may be differentially expressed in strain
      Becker versus strain Newman. The strain dependency of the CP8 expression
      established in vitro was also seen in lung tissue sections of patients with
      cystic fibrosis infected with CP8-positive S. aureus strains.

PMID- 11443097
TI  - The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of
      high-frequency phenotypic switching in Candida albicans.
AB  - Five histone deacetylase genes (HDA1, RPD3, HOS1, HOS2, and HOS3) have been
      cloned from Candida albicans and characterized. Sequence analysis and comparison
      with 17 additional deacetylases resulted in a phylogenetic tree composed of three
      major groups. Transcription of the deacetylases HDA1 and RPD3 is down-regulated
      in the opaque phase of the white-opaque transition in strain WO-1. HOS3 is
      selectively transcribed as a 2.5-kb transcript in the white phase and as a less
      abundant 2.3-kb transcript in the opaque phase. HDA1 and RPD3 were independently
      deleted in strain WO-1, and both switching between the white and opaque phases
      and the downstream regulation of phase-specific genes were analyzed. Deletion of
      HDA1 resulted in an increase in the frequency of switching from the white phase
      to the opaque phase, but had no effect on the frequency of switching from the
      opaque phase to the white phase. Deletion of RPD3 resulted in an increase in the
      frequency of switching in both directions. Deletion of HDA1 resulted in reduced
      white-phase-specific expression of the EFG1 3.2-kb transcript, but had no
      significant effect on white-phase-specific expression of WH11 or opaque-phase
      specific expression of OP4, SAP1, and SAP3. Deletion of RPD3 resulted in reduced
      opaque-phase-specific expression of OP4, SAP1, and SAP3 and a slight reduction of
      white-phase-specific expression of WH11 and 3.2-kb EFG1. Deletion of neither HDA1
      nor RPD3 affected the high level of white-phase expression and the low level of
      opaque-phase expression of the MADS box protein gene MCM1, which has been
      implicated in the regulation of opaque-phase-specific gene expression. In
      addition, there was no effect on the phase-regulated levels of expression of the
      other deacetylase genes. These results demonstrate that the two deacetylase genes
      HDA1 and RPD3 play distinct roles in the suppression of switching, that the two
      play distinct and selective roles in the regulation of phase-specific genes, and
      that the deacetylases are in turn regulated by switching.

PMID- 11443098
TI  - Evolution of an autotransporter: domain shuffling and lateral transfer from
      pathogenic Haemophilus to Neisseria.
AB  - The genomes of pathogenic Haemophilus influenzae strains are larger than that of
      Rd KW20 (Rd), the nonpathogenic laboratory strain whose genome has been
      sequenced. To identify potential virulence genes, we examined genes possessed by
      Int1, an invasive nonencapsulated isolate from a meningitis patient, but absent
      from Rd. Int1 was found to have a novel gene termed lav, predicted to encode a
      member of the AIDA-I/VirG/PerT family of virulence-associated autotransporters
      (ATs). Associated with lav are multiple repeats of the tetranucleotide GCAA,
      implicated in translational phase variation of surface molecules. Laterally
      acquired by H. influenzae, lav is restricted in distribution to a few pathogenic
      strains, including H. influenzae biotype aegyptius and Brazilian purpuric fever
      isolates. The DNA sequence of lav is surprisingly similar to that of a gene
      previously described for Neisseria meningitidis. Sequence comparisons suggest
      that lav was transferred relatively recently from Haemophilus to Neisseria,
      shortly before the divergence of N. meningitidis and Neisseria gonorrhoeae.
      Segments of lav predicted to encode passenger and beta-domains differ sharply in
      G+C base content, supporting the idea that AT genes have evolved by fusing
      domains which originated in different genomes. Homology and base sequence
      comparisons suggest that a novel biotype aegyptius AT arose by swapping an
      unrelated sequence for the passenger domain of lav. The unusually mobile lav
      locus joins a growing list of genes transferred from H. influenzae to Neisseria.
      Frequent gene exchange suggests a common pool of hypervariable contingency genes
      and may help to explain the origin of invasiveness in certain respiratory
      pathogens.

PMID- 11443099
TI  - Green fluorescent protein-Dal80p illuminates up to 16 distinct foci that
      colocalize with and exhibit the same behavior as chromosomal DNA proceeding
      through the cell cycle of Saccharomyces cerevisiae.
AB  - Four GATA family DNA binding proteins mediate nitrogen catabolite repression
      sensitive transcription in Saccharomyces cerevisiae. Gln3p and Gat1p are
      transcriptional activators, while Dal80p and Deh1p repress Gln3p- and Gat1p
      mediated transcription by competing with these activators for binding to DNA.
      Strong Dal80p binding to DNA is thought to result from C-terminal leucine zipper
      mediated dimerization. Many Dal80p binding site-homologous sequences are
      relatively evenly distributed across the S. cerevisiae genome, raising the
      possibility that Dal80p might be able to "stain" DNA. We demonstrate that cells
      containing enhanced green fluorescent protein-Dal80p (EGFP-Dal80p) exhibit up to
      16 fluorescent foci that colocalize with DAPI (4',6'-diamidino-2-phenylindole)
      positive material and follow DNA movement through the cell cycle, suggesting that
      EGFP-Dal80p may indeed be useful for monitoring yeast chromosomes in live cells
      and in real time.

PMID- 11443100
TI  - Roles for the Rhodobacter sphaeroides CcmA and CcmG proteins.
AB  - Rhodobacter sphaeroides cells containing an in-frame deletion within ccmA lack
      detectable soluble and membrane-bound c-type cytochromes and are unable to grow
      under conditions where these proteins are required. Only strains merodiploid for
      ccmABCDG were found after attempting to generate cells containing either a ccmG
      null mutation or a ccmA allele that should be polar on to expression of ccmBCDG,
      suggesting that CcmG has another important role in R. sphaeroides.

PMID- 11443101
TI  - Involvement of stringent factor RelA in expression of the alkaline protease gene
      aprE in Bacillus subtilis.
AB  - Expression of Bacillus subtilis aprE, encoding an extracellular alkaline
      protease, is positively regulated by phosphorylated DegU, the regulator of a two
      component regulatory system, DegS-DegU. We found that the expression of an aprE'
      'lacZ fusion was greatly reduced in a disruption mutant with a mutation of relA,
      which encodes the stringent factor RelA. The level of DegU in the relA mutant was
      similar to that in the wild-type cell. A relA degU double mutation did not result
      in a further decrease of the aprE'-'lacZ level found in a degU single mutant. The
      expression of the aprE'-'lacZ fusion in the relA mutant was stimulated by
      multicopy degR or the degU32(Hy) and degS200(Hy) mutations that cause the
      stabilization of phosphorylated DegU. Furthermore, the expression of sacB'-'lacZ,
      which is also dependent on phosphorylated DegU, was stimulated by the relA
      mutation, and this stimulation was not seen in the relA degU double mutant. These
      results show that RelA (or its product guanosine-3',5'-bisdiphosphate [pp Gpp])
      does not affect the phosphorylation of DegU and suggest that it participates in
      the expression of aprE and sacB through the regulation of DegU-dependent
      transcription.

PMID- 11443102
TI  - Virulence plasmid-borne spvB and spvC genes can replace the 90-kilobase plasmid
      in conferring virulence to Salmonella enterica serovar Typhimurium in
      subcutaneously inoculated mice.
AB  - In a mouse model of systemic infection, the spv genes carried on the Salmonella
      enterica serovar Typhimurium virulence plasmid increase the replication rate of
      salmonellae in host cells of the reticuloendothelial system, most likely within
      macrophages. A nonpolar deletion in the spvB gene greatly decreased virulence but
      could not be complemented by spvB alone. However, a low-copy-number plasmid
      expressing spvBC from a constitutive lacUV5 promoter did complement the spvB
      deletion. By examining a series of spv mutations and cloned spv sequences, we
      deduced that spvB and spvC could be sufficient to confer plasmid-mediated
      virulence to S. enterica serovar Typhimurium. The spvBC-bearing plasmid was
      capable of replacing all of the spv genes, as well as the entire virulence
      plasmid, of serovar Typhimurium for causing systemic infection in BALB/c mice
      after subcutaneous, but not oral, inoculation. A point mutation in the spvBC
      plasmid preventing translation but not transcription of spvC eliminated the
      ability of the plasmid to confer virulence. Therefore, it appears that both spvB
      and spvC encode the principal effector factors for Spv- and plasmid-mediated
      virulence of serovar Typhimurium.

PMID- 11443103
TI  - Activation by gene amplification of pitB, encoding a third phosphate transporter
      of Escherichia coli K-12.
AB  - Two systems for the uptake of inorganic phosphate (P(i)) in Escherichia coli,
      PitA and Pst, have been described. A revertant of a pitA pstS double mutant that
      could grow on P(i) was isolated. We demonstrate that the expression of a new P(i)
      transporter, PitB, is activated in this strain by a gene amplification event.

PMID- 11443104
TI  - ZitB (YbgR), a member of the cation diffusion facilitator family, is an
      additional zinc transporter in Escherichia coli.
AB  - The Escherichia coli zitB gene encodes a Zn(II) transporter belonging to the
      cation diffusion facilitator family. ZitB is specifically induced by zinc. ZitB
      expression on a plasmid rendered zntA-disrupted E. coli cells more resistant to
      zinc, and the cells exhibited reduced accumulation of (65)Zn, suggesting ZitB
      mediated efflux of zinc.

PMID- 11443105
TI  - Transcriptional analysis and regulation of expression of the ScrFI restriction
      modification system of Lactococcus lactis subsp. cremoris UC503.
AB  - ScrFI is a type II restriction-modification system from Lactococcus lactis which
      recognizes the nucleotide sequence 5'-CC downward arrow NGG-3', cleaving at the
      point indicated by the arrow, and it comprises an endonuclease gene that is
      flanked on either side by genes encoding two 5-methylcytosine methylases. An open
      reading frame (orfX) of unknown function is located immediately upstream of these
      genes. In this study Northern analysis was performed, and it revealed that orfX,
      scrFIBM, and scrFIR are cotranscribed as a single polygenic mRNA molecule, while
      scrFIAM is transcribed independently. 5' extension analysis indicated that the
      start site for the scrFIAM promoter was a thymine located 4 bp downstream of the 
      10 motif. The transcriptional start site for the orfX promoter was also found to
      be a thymine which is more atypically located 24 bp downstream of the -10 motif
      proximal to the start codon. A helix-turn-helix motif was identified at the N
      terminal end of one of the methylases (M.ScrFIA). In order to determine if this
      motif played a role in regulation of the ScrFI locus, M.ScrFIA was purified. It
      was then employed in gel retardation assays using fragments containing the two
      promoters found on the ScrFI operon, one located upstream of orfX and the other
      located just upstream of scrFIAM. M.ScrFIA was found to bind to the promoter
      region upstream of the gene encoding it, indicating that it may have a regulatory
      role. In further studies the two putative promoters were introduced into a vector
      (pAK80) upstream of a promoterless lacZ gene, and cloned fragments of the ScrFI
      locus were introduced in trans with each of these promoter constructs to
      investigate the effect on promoter activity. These results implicated M.ScrFIA in
      regulation of both promoters on the ScrFI locus.

PMID- 11443106
TI  - Loss of Pseudomonas aeruginosa PhpA aminopeptidase activity results in increased
      algD transcription.
AB  - Inactivation of Pseudomonas aeruginosa phpA, encoding a putative leucine
      aminopeptidase, results in increased transcription of algD. The homologous
      protein in Escherichia coli, PepA, is multifunctional, possessing independent
      aminopeptidase and DNA-binding activities. Here we provide in vitro evidence that
      PhpA is an aminopeptidase and show that this activity is the relevant property
      with regard to algD expression. This regulation occurred at the previously mapped
      algD transcription initiation site and was not due to activation of an
      alternative promoter.

PMID- 11443107
TI  - The potential role of proteoglycans in cationic lipid-mediated gene delivery.
      Studies of the interaction of cationic lipid-DNA complexes with model
      glycosaminoglycans.
AB  - Recent evidence supports a role for proteoglycans in polycation-mediated gene
      delivery. Therefore, the interaction of glycosaminoglycans with cationic lipid
      DNA complexes (CLDCs) has been characterized using a combination of biophysical
      approaches. At low ionic strength, CLDCs bind to heparin-derivatized Sepharose
      particles, with the ratio of cationic lipid to DNA controlling the binding.
      Incorporation of the helper lipids cholesterol or 1,2-dioleoyl
      phosphatidylethanolamine increases the amount of bound CLDC. Heparin also induces
      the aggregation of CLDCs, with cholesterol reducing this effect. Isothermal
      titration calorimetry demonstrates an endothermic heat for the binding of heparin
      to CLDCs at low ionic strength, whereas circular dichroism studies suggest a
      heparin-stimulated release of DNA from CLDCs at a greater than 20-fold charge
      excess. Increasing the ionic strength to 0.11 reduces CLDC binding to heparin
      beads, and greatly enhances the release of DNA from CLDCs by heparin. The ability
      of the cell surface glycosaminoglycan heparan sulfate to release DNA from CLDCs
      is more sensitive than heparin to the incorporation of the cholesterol or 1,2
      dioleoyl-phosphatidylethanolamine. Titration calorimetry reveals an exothermic
      heat for the interaction glycosaminoglycans with CLDCs at higher ionic strength.
      These results are consistent with the direct involvement of proteoglycans in
      transfection.

PMID- 11443108
TI  - Insulin up-regulates tumor necrosis factor-alpha production in macrophages
      through an extracellular-regulated kinase-dependent pathway.
AB  - Hyperinsulinemia has recently been reported as a risk factor for atherosclerotic
      diseases such as coronary heart disease; however, the effect of insulin on the
      development of atherosclerosis is not well understood. Here we have investigated
      the direct effect of insulin on macrophages, which are known to be important in
      the atherosclerotic process. We treated THP-1 macrophages with insulin (10(-7) m)
      and examined the gene expression using nucleic acid array systems. The results of
      array analysis showed that insulin stimulated gene expression of tumor necrosis
      factor-alpha (TNF-alpha) the most among all genes in the analysis. In addition,
      insulin administration to macrophages enhanced both mRNA expression and protein
      secretion of TNF-alpha in a dose-dependent manner. To determine the signaling
      pathway involved in this TNF-alpha response to insulin, we pretreated the cells
      with three distinct protein kinase inhibitors: wortmannin, PD98059, and SB203580.
      Only PD98059, which inhibits extracellular signal-regulated kinases, suppressed
      insulin-induced production of TNF-alpha mRNA and protein in THP-1 macrophages.
      These observations indicate that insulin stimulates TNF-alpha production in
      macrophages by regulating the expression of TNF-alpha mRNA and that the
      extracellular signal-regulated kinase signaling pathway may have a critical role
      in stimulating the production of TNF-alpha in response to insulin in macrophages.

PMID- 11443109
TI  - Transglutaminase 5 cross-links loricrin, involucrin, and small proline-rich
      proteins in vitro.
AB  - Transglutaminases (TGases) are seven enzymes, cross-linking proteins by gamma
      glutamil-epsilon-lysine bonds, four of which are expressed in the skin. A new
      member of the TGase family, TGase 5, has been identified recently, and in the
      present study we evaluated its role in keratinocyte differentiation in vitro. In
      addition to the previously described isoforms, full-length TGase 5 and Delta3
      (deletion of exon 3), we identified two new splicing variants, Delta11 and
      Delta3Delta11 (deletion of exons 11 or 3, 11). We expressed full-length TGase 5,
      Delta3, Delta11, and Delta3Delta11 isoforms in the keratinocyte and baculovirus
      systems. The results indicate that both full-length TGase 5 and Delta11 are
      active, whereas Delta3 and Delta3Delta11 have very low activity. Expression
      studies show that full-length TGase 5 is induced during the early stages of
      keratinocyte differentiation and is differently regulated in comparison with the
      other epidermal TGases. Kinetic and in vitro cross-linking experiments indicate
      that full-length TGase 5 is very efficient in using specific epidermal substrates
      (loricrin, involucrin, and SPR3). In keratinocyte expression system, TGase 5
      isoforms are retained in an intermediate filament-enriched fraction, suggesting
      its association with insoluble proteins. Indeed, TGase 5 co-localize with
      vimentin and it is able to cross-link vimentin in vitro.

PMID- 11443110
TI  - Identification and characterization of SppA, a novel light-inducible chloroplast
      protease complex associated with thylakoid membranes.
AB  - A new component of the chloroplast proteolytic machinery from Arabidopsis
      thaliana was identified as a SppA-type protease. The sequence of the mature
      protein, deduced from a full-length cDNA, displays 22% identity to the serine
      type protease IV (SppA) from Escherichia coli and 27% identity to Synechocystis
      SppA1 (sll1703) but lacks the putative transmembrane spanning segments predicted
      from the E. coli sequence. The N-terminal sequence exhibits typical features of a
      cleavable chloroplast stroma-targeting sequence. The chloroplast localization of
      SppA was confirmed by in organello import experiments using an in vitro
      expression system and by immunodetection with antigen-specific antisera.
      Subfractionation of intact chloroplasts demonstrated that SppA is associated
      exclusively with thylakoid membranes, predominantly stroma lamellae, and is a
      part of some high molecular mass complex of about 270 kDa that exhibits
      proteolytic activity. Treatments with chaotropic salts and proteases showed that
      SppA is largely exposed to the stroma but that it behaves as an intrinsic
      membrane protein that may have an unusual monotopic arrangement in the
      thylakoids. We demonstrate that SppA is a light-inducible protease and discuss
      its possible involvement in the light-dependent degradation of antenna and
      photosystem II complexes that both involve serine-type proteases.

PMID- 11443111
TI  - Phosphorylation and nuclear translocation of a regulator of G protein signaling
      (RGS10).
AB  - Heterotrimeric G proteins are involved in the transduction of hormonal and
      sensory signals across plasma membranes of eukaryotic cells. Hence, they are a
      critical point of control for a variety of agents that modulate cellular
      function. Activation of these proteins is dependent on GTP binding to their alpha
      (Galpha) subunits. Regulators of G protein signaling (RGS) bind specifically to
      activated Galpha proteins, potentiating the intrinsic GTPase activity of the
      Galpha proteins and thus expediting the termination of Galpha signaling. Although
      there are several points in most G protein controlled signaling pathways that are
      affected by reversible covalent modification, little evidence has been shown
      addressing whether or not the functions of RGS proteins are themselves regulated
      by such modifications. We report in this study the acute functional regulation of
      RGS10 thru the specific and inducible phosphorylation of RGS10 protein at serine
      168 by cAMP-dependent kinase A. This phosphorylation nullifies the RGS10 activity
      at the plasma membrane, which controls the G protein-dependent activation of the
      inwardly rectifying potassium channel. Surprisingly, the phosphorylation-mediated
      attenuation of RGS10 activity was not manifested in an alteration of its ability
      to accelerate GTPase activity of Galpha. Rather, the phosphorylation event
      correlates with translocation of RGS10 from the plasma membrane and cytosol into
      the nucleus.

PMID- 11443112
TI  - Identification and characterization of RRM-containing coactivator activator
      (CoAA) as TRBP-interacting protein, and its splice variant as a coactivator
      modulator (CoAM).
AB  - We previously cloned and characterized thyroid hormone receptor-binding protein
      (TRBP) as an LXXLL-containing general coactivator that associates with
      coactivator complexes through its C terminus. To identify protein cofactors for
      TRBP action, a Sos-Ras yeast two-hybrid cDNA library was screened using TRBP C
      terminus as bait. A novel coactivator was isolated, coactivator activator (CoAA),
      that specifically associates with TRBP. Human CoAA is composed of 669 amino acids
      with a TRBP-interacting domain and two highly conserved RNA recognition motifs
      (RRM) commonly found in ribonucleoproteins. A splice variant lacking the entire
      TRBP-interacting domain was also isolated as a coactivator modulator (CoAM), a
      156-amino acid protein containing only the RRM region. Human CoAA and CoAM mRNAs
      are encoded by a single gene located on chromosome 11q13; alternative splicing in
      exon 2 of CoAA yields CoAM. CoAA interacts with both TRBP and p300 in vitro. In
      addition, CoAA potently coactivates transcription mediated by multiple hormone
      response elements and acts synergistically with TRBP and CREB-binding protein
      (CBP). Furthermore, CoAA is associated with the DNA-dependent protein kinase
      poly(ADP-ribose) polymerase complex. Strikingly, CoAM, which lacks a TRBP
      interacting domain, strongly represses both TRBP and CBP action suggesting that
      CoAM may modulate endogenous CoAA function. These data suggest that CoAA may
      serve as a mediator of coactivators such as TRBP in gene activation.

PMID- 11443113
TI  - Site-directed mutagenesis of acyl carrier protein (ACP) reveals amino acid
      residues involved in ACP structure and acyl-ACP synthetase activity.
AB  - Acyl carrier protein (ACP) interacts with many different enzymes during the
      synthesis of fatty acids, phospholipids, and other specialized products in
      bacteria. To examine the structural and functional roles of amino acids
      previously implicated in interactions between the ACP polypeptide and fatty acids
      attached to the phosphopantetheine prosthetic group, recombinant Vibrio harveyi
      ACP and mutant derivatives of conserved residues Phe-50, Ile-54, Ala-59, and Tyr
      71 were prepared from glutathione S-transferase fusion proteins. Circular
      dichroism revealed that, unlike Escherichia coli ACP, V. harveyi-derived ACPs are
      unfolded at neutral pH in the absence of divalent cations; all except F50A and
      I54A recovered native conformation upon addition of MgCl(2). Mutant I54A was not
      processed to the holo form by ACP synthase. Some mutations significantly
      decreased catalytic efficiency of ACP fatty acylation by V. harveyi acyl-ACP
      synthetase relative to recombinant ACP, e.g. F50A (4%), I54L (20%), and I54V
      (31%), whereas others (V12G, Y71A, and A59G) had less effect. By contrast, all
      myristoylated ACPs examined were effective substrates for the luminescence
      specific V. harveyi myristoyl-ACP thioesterase. Conformationally sensitive gel
      electrophoresis at pH 9 indicated that fatty acid attachment stabilizes mutant
      ACPs in a chain length-dependent manner, although stabilization was decreased for
      mutants F50A and A59G. Our results indicate that (i) residues Ile-54 and Phe-50
      are important in maintaining native ACP conformation, (ii) residue Ala-59 may be
      directly involved in stabilization of ACP structure by acyl chain binding, and
      (iii) acyl-ACP synthetase requires native ACP conformation and involves
      interaction with fatty acid binding pocket residues, whereas myristoyl-ACP
      thioesterase is insensitive to acyl donor structure.

PMID- 11443114
TI  - Down-regulation of the alpha-Gal epitope expression in N-glycans of swine
      endothelial cells by transfection with the N-acetylglucosaminyltransferase III
      gene. Modulation of the biosynthesis of terminal structures by a bisecting
      GlcNAc.
AB  - The down-regulation of the alpha-Gal epitope (Galalpha1,3Galbeta-R) in swine
      tissues would be highly desirable, in terms of preventing hyperacute rejection in
      pig-to-human xenotransplantation. In an earlier study, we reported that the
      introduction of the beta1,4-N-acetylglucosaminyltransferase (GnT) III gene into
      swine endothelial cells resulted in a substantial reduction in the expression of
      the alpha-Gal epitope. In this study, we report on the mechanism for this down
      regulation of the alpha-Gal epitope by means of structural and kinetic analyses.
      The structural analyses revealed that the amount of N-linked oligosaccharides
      bearing the alpha-Gal epitopes in the GnT-III-transfected cells was less than 10%
      that in parental cells, due to the alteration of the terminal structures as well
      as a decrease in branch formation. In addition, it appeared that the addition of
      a bisecting GlcNAc, which is catalyzed by GnT-III, leads to a more efficient
      sialylation rather than alpha-galactosylation. In vitro kinetic analyses showed
      that the bisecting GlcNAc has an inhibitory effect on alpha-galactosylation, but
      does not significantly affect the sialylation. These results suggest that the
      bisecting GlcNAc in the core is capable of modifying the biosynthesis of the
      terminal structures via its differential effects on the capping
      glycosyltransferase reactions. The findings may contribute to the development of
      a novel strategy to eliminate carbohydrate xenoantigens.

PMID- 11443115
TI  - Glucose-induced toxicity in insulin-producing pituitary cells that coexpress
      GLUT2 and glucokinase. Implications for metabolic engineering.
AB  - We have shown that intermediate lobe (IL) pituitary cells can be engineered to
      produce sufficient amounts of insulin (ins) to cure diabetes in nonobese diabetic
      mice but, unlike transplanted islets, ILins cells evade immune attack. To confer
      glucose-sensing capabilities into these cells, they were further modified with
      recombinant adenoviruses to express high levels of GLUT2 and the beta-cell
      isoform of glucokinase (GK). Although expression of GLUT2 alone had negligible
      effects on glucose usage and lactate production, expression of GK alone resulted
      in approximately 2-fold increase in glycolytic flux within the physiological (3
      20 mm) glucose range. GLUT2/GK coexpression further increased glycolytic flux at
      20 mm glucose but disproportionately increased flux at 3 mm glucose. Despite
      enhanced glycolytic fluxes, GLUT2/GK-coexpressing cells showed glucose dose
      dependent accumulation of hexose phosphates, depletion of intracellular ATP, and
      severe apoptotic cell death. These studies demonstrate that glucose-sensing
      properties can be introduced into non-islet cells by the single expression of GK
      and that glucose responsiveness can be augmented by the coexpression of GLUT2.
      However, in the metabolic engineering of surrogate beta cells, it is critical
      that the levels of the components be closely optimized to ensure their
      physiological function and to avoid the deleterious consequences of glucose
      induced toxicity.

PMID- 11443116
TI  - Phosphoinositide 3-kinase gamma mediates angiotensin II-induced stimulation of L
      type calcium channels in vascular myocytes.
AB  - Previous results have shown that in rat portal vein myocytes the betagamma dimer
      of the G(13) protein transduces the angiotensin II-induced stimulation of calcium
      channels and increase in intracellular Ca(2+) concentration through activation of
      phosphoinositide 3-kinase (PI3K). In the present work we determined which class I
      PI3K isoforms were involved in this regulation. Western blot analysis indicated
      that rat portal vein myocytes expressed only PI3Kalpha and PI3Kgamma and no other
      class I PI3K isoforms. In the intracellular presence of an anti-p110gamma
      antibody infused by the patch clamp pipette, both angiotensin II- and Gbetagamma
      mediated stimulation of Ca(2+) channel current were inhibited, whereas
      intracellular application of an anti-p110alpha antibody had no effect. The anti
      PI3Kgamma antibody also inhibited the angiotensin II- and Gbetagamma-induced
      production of phosphatidylinositol 3,4,5-trisphosphate. In Indo-1 loaded cells,
      the angiotensin II-induced increase in [Ca(2+)](i) was inhibited by intracellular
      application of the anti-PI3Kgamma antibody, whereas the anti-PI3Kalpha antibody
      had no effect. The specificity of the anti-PI3Kgamma antibody used in functional
      experiments was ascertained by showing that this antibody did not recognize
      recombinant PI3Kalpha in Western blot experiments. Moreover, anti-PI3Kgamma
      antibody inhibited the stimulatory effect of intracellularly infused recombinant
      PI3Kgamma on Ca(2+) channel current without altering the effect of recombinant
      PI3Kalpha. Our results show that, although both PI3Kgamma and PI3Kalpha are
      expressed in vascular myocytes, the angiotensin II-induced stimulation of
      vascular L-type calcium channel and increase of [Ca(2+)](i) involves only the
      PI3Kgamma isoform.

PMID- 11443117
TI  - Pre-steady state quantification of the allosteric influence of Escherichia coli
      phosphofructokinase.
AB  - Stopped-flow kinetics was utilized to determine how allosteric activators and
      inhibitors of wild-type Escherichia coli phosphofructokinase influenced the
      kinetic rate and equilibrium constants of the binding of substrate fructose 6
      phosphate. Monitoring pre-steady state fluorescence intensity emission changes
      upon an addition of a ligand to the enzyme was possible by a unique tryptophan
      per subunit of the enzyme. Binding of fructose 6-phosphate to the enzyme
      displayed a two-step process, with a fast complex formation step followed by a
      relatively slower isomerization step. Systematic addition of fructose 6-phosphate
      to phosphofructokinase in the absence and presence of several fixed
      concentrations of phosphoenolpyruvate indicated that the inhibitor binds to the
      enzyme concurrently with the substrate, forming a ternary complex and inducing a
      conformational change, rather than a displacement of the equilibrium as predicted
      by the classical two-state model (Monod, J., Wyman, J., and Changeux, J. P.
      (1965) J. Mol. Biol. 12, 88-118). The activator, MgADP, also altered the affinity
      of fructose 6-phosphate to the enzyme by forming a ternary complex. Furthermore,
      both phosphoenolpyruvate and MgADP act by influencing the fast complex formation
      step while leaving the slower enzyme isomerization step essentially unchanged.

PMID- 11443118
TI  - CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays
      a role in Lyn-mediated receptor signaling.
AB  - The erythropoietin (Epo) receptor transduces its signals by activating physically
      associated tyrosine kinases, mainly Jak2 and Lyn, and thereby inducing tyrosine
      phosphorylation of various substrates including the Epo receptor (EpoR) itself.
      We previously demonstrated that, in Epo-stimulated cells, an adapter protein,
      CrkL, becomes tyrosine-phosphorylated, physically associates with Shc, SHP-2, and
      Cbl, and plays a role in activation of the Ras/Erk signaling pathway. Here, we
      demonstrate that Epo induces binding of CrkL to the tyrosine-phosphorylated EpoR
      and SHIP1 in 32D/EpoR-Wt cells overexpressing CrkL. In vitro binding studies
      showed that the CrkL SH2 domain directly mediates the EpoR binding, which was
      specifically inhibited by a synthetic phosphopeptide corresponding to the amino
      acid sequences at Tyr(460) in the cytoplasmic domain of EpoR. The CrkL SH2 domain
      was also required for tyrosine phosphorylation of CrkL in Epo-stimulated cells.
      Overexpression of Lyn induced constitutive phosphorylation of CrkL and activation
      of Erk, whereas that of a Lyn mutant lacking the tyrosine kinase domain
      attenuated the Epo-induced phosphorylation of CrkL and activation of Erk.
      Furthermore, Lyn, but not Jak2, phosphorylated CrkL on tyrosine in in vitro
      kinase assays. Together, the present study suggests that, upon Epo stimulation,
      CrkL is recruited to the EpoR through interaction between the CrkL SH2 domain and
      phosphorylated Tyr(460) in the EpoR cytoplasmic domain and undergoes tyrosine
      phosphorylation by receptor-associated Lyn to activate the downstream signaling
      pathway leading to the activation of Erk and Elk-1.

PMID- 11443119
TI  - The photocycle of a flavin-binding domain of the blue light photoreceptor
      phototropin.
AB  - The plant blue light receptor, phot1, a member of the phototropin family, is a
      plasma membrane-associated flavoprotein that contains two ( approximately 110
      amino acids) flavin-binding domains, LOV1 and LOV2, within its N terminus and a
      typical serine-threonine protein kinase domain at its C terminus. The LOV (light,
      oxygen, and voltage) domains belong to the PAS domain superfamily of sensor
      proteins. In response to blue light, phototropins undergo autophosphorylation. E.
      coli-expressed LOV domains bind riboflavin-5'-monophosphate, are photochemically
      active, and have major absorption peaks at 360 and 450 nm, with the 450 nm peak
      having vibronic structure at 425 and 475 nm. These spectral features correspond
      to the action spectrum for phototropism in higher plants. Blue light excitation
      of the LOV2 domain generates, in less than 30 ns, a transient approximately 660
      nm-absorbing species that spectroscopically resembles a flavin triplet state.
      This putative triplet state subsequently decays with a 4-micros time constant
      into a 390 nm-absorbing metastable form. The LOV2 domain (450 nm) recovers
      spontaneously with half-times of approximately 50 s. It has been shown that the
      metastable species is likely a flavin-cysteine (Cys(39) thiol) adduct at the
      flavin C(4a) position. A LOV2C39A mutant generates the early photoproduct but not
      the adduct. Titrations of LOV2 using chromophore fluorescence as an indicator
      suggest that Cys(39) exists as a thiolate.

PMID- 11443120
TI  - Acetylcholinesterase H and T dimers are associated through the same contact.
      Mutations at this interface interfere with the C-terminal T peptide, inducing
      degradation rather than secretion.
AB  - Acetylcholinesterase (AChE) exists as AChE(H) and AChE(T) subunits, which differ
      by their C-terminal H or T peptides, generating glycophosphatidylinositol
      anchored dimers and various oligomers, respectively. We introduced mutations in
      the four-helix bundle interface of glycophosphatidylinositol-anchored dimers, and
      analyzed their effect on the production and oligomerization of AChE(H), of
      AChE(T), and of truncated subunits, AChE(C) (without H or T peptide).
      Dimerization was reduced for all types of subunits, showing that they interact
      through the same contact zone; the formation of amphiphilic tetramers (Torpedo
      AChE(T)) and 13.5 S oligomers (rat AChE(T)) was also suppressed. Oligomerization
      appeared totally blocked by introduction of an N-linked glycan on the surface of
      helix alpha(7,8). Other point mutations did not affect the synthesis or the
      catalytic properties of AChE but reduced or blocked the secretion of AChE(T)
      subunits. Secretion of AChE(T) was partially restored by co-expression with Q(N),
      a secretable protein containing a proline-rich attachment domain (PRAD); Q(N)
      organized PRAD-linked tetramers, except for the N-glycosylated mutants. Thus, the
      simultaneous presence of an abnormal four-helix bundle zone and an exposed T
      peptide targeted the enzyme toward degradation, indicating a cross-talk between
      the catalytic and tetramerization domains.

PMID- 11443121
TI  - Sterol regulatory element-binding protein-1c mimics the negative effect of
      insulin on phosphoenolpyruvate carboxykinase (GTP) gene transcription.
AB  - We have assessed the potential role of sterol regulatory element-binding protein
      1c (SREBP-1c) on the transcription of the gene for the cytosolic form of
      phosphoenolpyruvate carboxykinase (GTP) (EC ) (PEPCK-C). SREBP-1c introduced into
      primary hepatocytes with an adenovirus vector caused a total loss of PEPCK-C mRNA
      and a marked induction of fatty acid synthase mRNA that directly coincided with
      the appearance of SREBP-1c in the hepatocytes. It also blocked the induction of
      PEPCK-C mRNA by cAMP and dexamethasone in these cells. In contrast, a dominant
      negative form of SREBP-1c (dnSREBP-1c) stimulated the accumulation of PEPCK-C
      mRNA in these cells. SREBP-1c completely blocked the induction of PEPCK-C gene
      transcription by the catalytic subunit of protein kinase A (PKA), and increasing
      concentrations of dnSREBP-1c reversed the negative effect of insulin on
      transcription from the PEPCK-C gene promoter in WT-IR cells. The more than 10
      fold induction of PKA-stimulated PEPCK-C gene transcription caused by the co
      activator CBP, was also blocked by SREBP-1c. In addition, dnSREBP-1c reversed the
      strong negative effect of E1A and NF1 on PKA-stimulated transcription from the
      PEPCK-C gene promoter. An analysis of the possible site of action of SREBP-1c
      using stepwise truncations of the PEPCK-C gene promoter indicated that the
      negative effect of SREBP-1c on transcription is exerted at a site between -355
      and -277. We conclude that SREBP-1c is an intermediate in the action of insulin
      on PEPCK-C gene transcription in the liver and acts by blocking the stimulatory
      effect cAMP that is mediated via an interaction with cAMP-binding protein.

PMID- 11443122
TI  - Exposure of bovine cytochrome c oxidase to high triton X-100 or to alkaline
      conditions causes a dramatic change in the rate of reduction of compound F.
AB  - The final step in the catalytic cycle of cytochrome oxidase, the reduction of
      oxyferryl heme a(3) in compound F, was investigated using a binuclear
      polypyridine ruthenium complex ([Ru(bipyridine)(2)](2)(1,4-bis[2-(4'-methyl-2, 2'
      bipyrid-4-yl)ethenyl]benzene)(PF(6))(4)) as a photoactive reducing agent. In the
      untreated dimeric enzyme, the rate constant for reduction of compound F decreased
      from 700 s(-1) to 200 s(-1) as the pH was increased from 7.5 to 9.5. Incubation
      of dimeric enzyme at pH 10 led to an increase in the rate constant to 1650 s(-1),
      which was independent of pH between pH 7.4 and 10. This treatment resulted in a
      decrease in the sedimentation coefficient consistent with the irreversible
      conversion of the enzyme to a monomeric form. Similar results were obtained when
      the enzyme was incubated with Triton X-100 at pH 8.0. These treatments, which
      have traditionally been used to convert dimeric enzyme to monomeric form, have no
      effect on the steady-state activity. The data indicate that either the conversion
      of the bovine oxidase to a monomeric form or some structural change coincident
      with this conversion strongly influences the rate constant of this step in the
      catalytic cycle, perhaps by influencing the proton access to the heme-copper
      binuclear center.

PMID- 11443123
TI  - Cyclin-dependent kinase 5 promotes insulin exocytosis.
AB  - Cyclin-dependent kinase 5 (Cdk5) is widely expressed although kinase activity has
      been described preferentially in neuronal systems. Cdk5 has an impact on actin
      polymerization during neuronal migration and neurite outgrowth and deregulation
      of the kinase has been implicated in the promotion of neurodegeneration. Recently
      it was shown that Cdk5 modulates dopamine signaling in neurons by regulating
      DARPP-32 function. In addition, Cdk5 phosphorylates munc-18 and synapsin I, two
      essential components of the exocytotic machinery. We have shown by reverse
      transcriptase-polymerase chain reaction, immunocytochemistry, and Western
      blotting that Cdk5 is present in the insulin-secreting pancreatic beta-cell.
      Subcellular fractionation of isolated beta-cells revealed a glucose-induced
      translocation of membrane-bound Cdk5 protein to lower density fractions.
      Inhibition of Cdk5 with roscovitine reduced insulin secretion with approximately
      35% compared with control after glucose stimulation and with approximately 65%
      after depolarization with glucose and KCl. Capacitance measurements performed on
      single beta-cells that expressed a dominant-negative Cdk5 mutant showed impaired
      exocytosis. The effect on exocytosis by Cdk5 appeared to be independent of
      changes in free cytoplasmic Ca(2+) concentration. Taken together these results
      show that Cdk5 is present in beta-cells and acts as a positive regulator of
      insulin exocytosis.

PMID- 11443124
TI  - 5-azaC treatment enhances expression of transforming growth factor-beta receptors
      through down-regulation of Sp3.
AB  - We have previously reported that Sp3 acts as a transcriptional repressor of
      transforming growth factor-beta receptors type I (RI) and type II (RII). We now
      present data suggesting that treatment of MCF-7L breast and GEO colon cancer
      cells with 5-aza cytidine (5-azaC) leads to down-regulation of Sp3 and the
      concomitant induction of RI and RII. Western blot and gel shift analyses on 5
      azaC-treated MCF-7L and GEO nuclear extracts indicated reduced Sp3 protein levels
      and decreased binding of Sp3 protein to radiolabeled consensus Sp1
      oligonucleotide. Southwestern analysis detected decreased binding of Sp3 to RI
      and RII promoters in 5-azaC-treated MCF-7L and GEO cells, suggesting a
      correlation between decreased Sp3 binding and enhanced RI and RII expression in
      these cells. Reverse transcription-polymerase chain reaction and nuclear run-on
      data from 5-azaC-treated MCF-7L and GEO cells indicated down-regulation of Sp3
      mRNA as a result of decreased transcription of Sp3. We reported earlier that 5
      azaC treatment induces RI and RII expression through increased Sp1 protein
      levels/activities in these cells. These studies demonstrate that the effect of 5
      azaC involves a combination of effects on Sp1 and Sp3.

PMID- 11443125
TI  - The role of the cysteine residues of ThiI in the generation of 4-thiouridine in
      tRNA.
AB  - The enzyme ThiI is common to the biosynthetic pathways leading to both thiamin
      and 4-thiouridine in tRNA. We earlier noted the presence of a motif shared with
      sulfurtransferases, and we reported that the cysteine residue (Cys-456 of
      Escherichia coli ThiI) found in this motif is essential for activity (Palenchar,
      P. M., Buck, C. J., Cheng, H., Larson, T. J., and Mueller, E. G. (2000) J. Biol.
      Chem. 275, 8283-8286). In light of that finding and the report of the involvement
      of the protein IscS in the reaction (Kambampati, R., and Lauhon, C. T. (1999)
      Biochemistry 38, 16561-16568), we proposed two mechanisms for the sulfur transfer
      mediated by ThiI, and both suggested possible involvement of the thiol group of
      another cysteine residue in ThiI. We have now substituted each of the cysteine
      residues with alanine and characterized the effect on activity in vivo and in
      vitro. Cys-108 and Cys-202 were converted to alanine with no significant effect
      on ThiI activity, and C207A ThiI was only mildly impaired. Substitution of Cys
      344, the only cysteine residue conserved among all sequenced ThiI, resulted in
      the loss of function in vivo and a 2700-fold reduction in activity measured in
      vitro. We also examined the possibility that ThiI contains an iron-sulfur cluster
      or disulfide bonds in the resting state, and we found no evidence to support the
      presence of either species. We propose that Cys-344 forms a disulfide bond with
      Cys-456 during turnover, and we present evidence that a disulfide bond can form
      between these two residues in native ThiI and that disulfide bonds do form in
      ThiI during turnover. We also discuss the relevance of these findings to the
      biosynthesis of thiamin and iron-sulfur clusters.

PMID- 11443126
TI  - Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin
      receptor regulates its coupling to G(s)-, to G(i)-, and to G(q)-coupled effector
      signaling.
AB  - The prostacyclin receptor (IP) is primarily coupled to G alpha(s)-dependent
      activation of adenylyl cyclase; however, a number of studies indicate that the IP
      may couple to other secondary effector systems perhaps in a species-specific
      manner. In the current study, we investigated the specificity of G
      protein:effector coupling by the mouse (m) IP overexpressed in human embryonic
      kidney 293 cells and endogenously expressed in murine erythroleukemia cells. The
      mIP exhibited efficient G alpha(s) coupling and concentration-dependent increases
      in cAMP generation in response to the IP agonist cicaprost; however, mIP also
      coupled to G alpha(i) decreasing the levels of cAMP in forskolin-treated cells.
      mIP coupling to G alpha(i) was pertussis toxin-sensitive and was dependent on
      protein kinase (PK) A activation status. In addition, the mIP coupled to
      phospholipase C (PLC) activation in a pertussis toxin-insensitive, G alpha(i)-, G
      beta gamma-, and PKC-independent but in a G alpha(q)- and PKA-dependent manner.
      Whole cell phosphorylation assays demonstrated that the mIP undergoes cicaprost
      induced PKA phosphorylation. mIP(S357A), a site-directed mutant of mIP,
      efficiently coupled to G alpha(s) but failed to couple to G alpha(i) or to
      efficiently couple to G alpha(q):PLC. Moreover, mIP(S357A) did not undergo
      cicaprost-induced phosphorylation confirming that Ser(357) is the target residue
      for PKA-dependent phosphorylation. Finally, co-precipitation experiments
      permitted the detection of G alpha(s), G alpha(i), and G alpha(q) in the
      immunoprecipitates of mIP, whereas only G alpha(s) was co-precipitated with
      mIP(S357A) indicating that Ser(357) of mIP is essential for G alpha(i) and G
      alpha(q) interaction. Moreover, inhibition of PKA blocked co-precipitation of mIP
      with G alpha(i) or G alpha(q). Taken together our data indicate that the mIP, in
      addition to coupling to G alpha(s), couples to G alpha(i) and G alpha(q);
      however, G alpha(i) and G alpha(q) coupling is dependent on initial cicaprost
      induced mIP:G alpha(s) coupling and phosphorylation of mIP by cAMP-dependent PKA
      where Ser(357) was identified as the target residue for PKA phosphorylation.

PMID- 11443127
TI  - Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic
      abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3.
AB  - Sphingosine 1-phosphate (S1P) exerts diverse physiological actions by activating
      its cognate G protein-coupled receptors. Five S1P receptors have been identified
      in mammals: LP(B1)/EDG-1, LP(B2)/H218/AGR16/EDG-5, LP(B3)/EDG-3, LP(B4)/NRG-1/EDG
      8, and LP(C1)/EDG-6. One of these receptors, LP(B1), has recently been shown to
      be essential for mouse embryonic development. Here we disrupted the lp(B3) gene
      in mice, resulting in the complete absence of lp(B3) gene, transcript, and LP(B3)
      protein. LP(B3)-null mice were viable and fertile and developed normally with no
      obvious phenotypic abnormality. We prepared mouse embryonic fibroblast (MEF)
      cells to examine effects of LP(B3) deletion on S1P-induced signal transduction
      pathways. Wild-type MEF cells expressed lp(B1), lp(B2), and lp(B3) but neither
      lp(B4) nor lp(C1), and they were highly responsive to S1P in phospholipase C
      (PLC) activation, adenylyl cyclase inhibition, and Rho activation. Identically
      prepared LP(B3)-null MEF cells showed significant decreases in PLC activation,
      slight decreases in adenylyl cyclase inhibition, and no change in Rho activation.
      Retrovirus-mediated rescue of the LP(B3) receptor in LP(B3)-null MEF cells
      restored S1P-dependent PLC activation and adenylyl cyclase inhibition. These
      results indicate a nonessential role for LP(B3) in normal development of mouse
      but show nonredundant cellular signaling mediated by a single type of S1P
      receptor.

PMID- 11443128
TI  - A phosphorylation-regulated brake mechanism controls the initial endocytosis of
      opioid receptors but is not required for post-endocytic sorting to lysosomes.
AB  - The delta-opioid receptor (DOR) can undergo proteolytic down-regulation by
      endocytosis of receptors followed by sorting of internalized receptors to
      lysosomes. Although phosphorylation of the receptor is thought to play an
      important role in controlling receptor down-regulation, previous studies disagree
      on whether phosphorylation is actually required for the agonist-induced
      endocytosis of opioid receptors. Furthermore, no previous studies have determined
      whether phosphorylation is required for subsequent sorting of internalized
      receptors to lysosomes. We have addressed these questions by examining the
      endocytic trafficking of a series of mutant versions of DOR expressed in stably
      transfected HEK 293 cells. Our results confirm that phosphorylation is not
      required for agonist-induced endocytosis of truncated mutant receptors that lack
      the distal carboxyl-terminal cytoplasmic domain containing sites of regulatory
      phosphorylation. However, phosphorylation is required for endocytosis of full
      length receptors. Mutation of all serine/threonine residues located in the distal
      carboxyl-terminal tail domain of the full-length receptor to alanine creates
      functional mutant receptors that exhibit no detectable agonist-induced
      endocytosis. Substitution of these residues with aspartate restores the ability
      of mutant receptors to undergo agonist-induced endocytosis. Studies using green
      fluorescent protein-tagged versions of arrestin-3 suggest that the distal tail
      domain, when not phosphorylated, inhibits receptor-mediated recruitment of beta
      arrestins to the plasma membrane. Biochemical and radioligand binding studies
      indicate that, after endocytosis occurs, phosphorylation-defective mutant
      receptors traffic to lysosomes with similar kinetics as wild type receptors. We
      conclude that phosphorylation controls endocytic trafficking of opioid receptors
      primarily by regulating a "brake" mechanism that prevents endocytosis of full
      length receptors in the absence of phosphorylation. After endocytosis occurs,
      subsequent steps of membrane trafficking mediating sorting and transport to
      lysosomes do not require receptor phosphorylation.

PMID- 11443129
TI  - Differential cooperation between regulatory sequences required for human CD53
      gene expression.
AB  - CD53 is a tetraspanin protein mostly expressed in to the lymphoid-myeloid
      lineage. We have characterized the human CD53 gene regulatory region. Within the
      proximal 2 kilobases, and with opposite transcriptional orientation, is located
      the promoter-enhancer of a second gene, which does not affect CD53. Twenty-four
      copies of a CA dinucleotide repeat separate these two gene promoters. The
      proximal enhanceosome of the human CD53 gene is comprised between residues -266
      and +84, and can be subdivided into four major subregions, two of them within
      exon 1. Mutational analysis identified several cooperating sequences. An Sp1 and
      an ets-1 site, at positions -115 and +62, respectively, are essential for
      transcriptional competence in all cell lines. Five other regulatory sequences
      have a dual role, activator or down-regulator, depending on the cell line. At the
      end of the non-coding exon 1, +64 to +83, there is a second ets-1 regulatory
      element, which is required for high level of transcription, in cooperation with
      the Sp1 site, in K562 and Molt-4, but not in Namalwa cells, where it functions as
      a repressor. This Sp1 site also cooperates with another ets-1/PU.1 site at -172.
      Different cell types use different regulatory sequences in the enhanceosome for
      the expression of the same gene.

PMID- 11443130
TI  - Insulin rescues retinal neurons from apoptosis by a phosphatidylinositol 3
      kinase/Akt-mediated mechanism that reduces the activation of caspase-3.
AB  - The ability of insulin to protect neurons from apoptosis was examined in
      differentiated R28 cells, a neural cell line derived from the neonatal rat
      retina. Apoptosis was induced by serum deprivation, and the number of pyknotic
      cells was counted. p53 and Akt were examined by immunoblotting after serum
      deprivation and insulin treatment, and caspase-3 activation was examined by
      immunocytochemistry. Serum deprivation for 24 h caused approximately 20% of R28
      cells to undergo apoptosis, detected by both pyknosis and activation of caspase
      3. 10 nm insulin maximally reduced the amount of apoptosis with a similar potency
      as 1.3 nm (10 ng/ml) insulin-like growth factor 1, which acted as a positive
      control. Insulin induced serine phosphorylation of Akt, through the
      phosphatidylinositol (PI) 3-kinase pathway. Inhibition of PI 3-kinase with
      wortmannin or LY294002 blocked the ability of insulin to rescue the cells from
      apoptosis. SN50, a peptide inhibitor of NF-kappaB nuclear translocation, blocked
      the rescue effect of insulin, but neither insulin or serum deprivation induced
      phosphorylation of IkappaB. These results suggest that insulin is a survival
      factor for retinal neurons by activating the PI 3-kinase/Akt pathway and by
      reducing caspase-3 activation. The rescue effect of insulin does not appear to be
      mediated by NF-kappaB or p53. These data suggest that insulin provides trophic
      support for retinal neurons through a PI 3-kinase/Akt-dependent pathway.

PMID- 11443131
TI  - Glucosylceramide synthases, a gene family responsible for the biosynthesis of
      glucosphingolipids in animals, plants, and fungi.
AB  - Glucosylceramides are membrane lipids in most eukaryotic organisms and in a few
      bacteria. The physiological functions of these glycolipids have only been
      documented in mammalian cells, whereas very little information is available of
      their roles in plants, fungi, and bacteria. In an attempt to establish
      appropriate experimental systems to study glucosylceramide functions in these
      organisms, we performed a systematic functional analysis of a glycosyltransferase
      gene family with members of animal, plant, fungal, and bacterial origin. Deletion
      of such putative glycosyltransferase genes in Candida albicans and Pichia
      pastoris resulted in the complete loss of glucosylceramides. When the
      corresponding knock-out strains were used as host cells for homologous or
      heterologous expression of candidate glycosyltransferase genes, five novel
      glucosylceramide synthase (UDP-glucose:ceramide glucosyltransferase) genes were
      identified from the plant Gossypium arboreum (cotton), the nematode
      Caenorhabditis elegans, and the fungi Magnaporthe grisea, Candida albicans, and
      P. pastoris. The glycosyltransferase gene expressions led to the biosynthesis of
      different molecular species of glucosylceramides that contained either C18 or
      very long chain fatty acids. The latter are usually channeled exclusively into
      inositol-containing sphingolipids known from Saccharomyces cerevisiae and other
      yeasts. Implications for the biosynthesis, transport, and function of
      sphingolipids will be discussed.

PMID- 11443132
TI  - Oxidative stress induces neuronal death by recruiting a protease and phosphatase
      gated mechanism.
AB  - Reactive oxygen species (ROS) cause death of cerebellar granule neurons. Here, a
      15-min pulse of H(2)O(2) (100 microm) induced an active process of neuronal death
      distinct from apoptosis. Oxidative stress activated a caspase-independent but
      calpain-dependent decline of calcium/calmodulin-dependent protein kinase IV and
      cAMP- responsive element-binding protein (CREB). Calpain inhibitors restored
      calcium/calmodulin-dependent protein kinase IV and CREB but did not influence
      phosphorylated CREB levels or survival, indicating recruitment of an additional
      dephosphorylation process. Co-treatment with calpain and serine/threonine
      phosphatase inhibitors restored pCREB levels and rescued neurons. This
      phosphatase-activated signaling pathway was shown to be dependent on de novo
      protein synthesis. Further, gene transfer studies revealed that CREB is a common
      final effector of both apoptosis and ROS-induced death. Our data indicate that
      dephosphorylation and proteolytic signaling mechanisms underlie ROS-induced
      programmed cell death.

PMID- 11443133
TI  - Different roles for basic and aromatic amino acids in conserved region 2 of
      Escherichia coli sigma(70) in the nucleation and maintenance of the single
      stranded DNA bubble in open RNA polymerase-promoter complexes.
AB  - Amino acid residues in region 2 of final sigma(70) have been shown to play an
      important role in the strand separation step that is necessary for formation of
      the functional or open RNA polymerase-promoter complex. Here we present a
      comparison of the roles of basic and aromatic amino acids in the accomplishment
      of this process, using RNA polymerase bearing alanine substitutions for both
      types of amino acids in region 2. We determined the effects of the substitutions
      on the kinetics of open complex formation, as well as on the ability of the RNA
      polymerase to form complexes with single-stranded DNA, and with forked DNA
      duplexes carrying a single-stranded overhang consisting of bases in the -10
      region. We concluded that two basic amino acids (Lys(414) and Lys(418)) are
      important for promoter binding and demonstrated distinct roles, at a subsequent
      step, for two aromatic amino acids (Tyr(430) and Trp(433)). It is likely that
      these four amino acids, which are close to each other in the structure of final
      sigma(70), together are involved in the nucleation of the strand separation
      process.

PMID- 11443134
TI  - Regulation of Raf by Akt controls growth and differentiation in vascular smooth
      muscle cells.
AB  - The stimulation of platelet-derived growth factor (PDGF) receptors shifts
      vascular smooth muscle (VSM) cells toward a more proliferative phenotype.
      Thrombin activates the same signaling cascades in VSM cells, namely the
      Ras/Raf/MEK/ERK and the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathways.
      Nonetheless, thrombin was not mitogenic, but rather increased the expression of
      the smooth muscle-specific myosin heavy chain (SM-MHC) indicative of an in vitro
      re-differentiation of VSM cells. A more detailed analysis of the temporal pattern
      and relative signal intensities revealed marked differences. The strong and
      biphasic phosphorylation of ERK1/2 in response to thrombin correlated with its
      ability to increase the activity of the SM-MHC promoter whereas Akt was only
      partially and transiently phosphorylated. By contrast, PDGF, a potent mitogen in
      VSM cells, induced a short-lived ERK1/2 phosphorylation but a complete and
      sustained phosphorylation of Akt. The phosphorylated form of Akt physically
      interacted with Raf. Moreover, Akt phosphorylated Raf at Ser(259), resulting in a
      reduced Raf kinase activity and a termination of MEK and ERK1/2 phosphorylation.
      Disruption of the PI 3-kinase signaling prevented the PDGF-induced Akt and Raf
      Ser(259) phosphorylation. Under these conditions, PDGF elicited a more sustained
      MEK and ERK phosphorylation and increased SM-MHC promoter activity. Consistently,
      in cells that express dominant negative Akt, PDGF increased SM-MHC promoter
      activity. Furthermore, expression of constitutively active Akt blocked the
      thrombin-stimulated SM-MHC promoter activity. Thus, we present evidence that the
      balance and cross-regulation between the PI 3-kinase/Akt and Ras/Raf/MEK
      signaling cascades determine the temporal pattern of ERK1/2 phosphorylation and
      may thereby guide the phenotypic modulation of vascular smooth muscle cells.

PMID- 11443135
TI  - Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base
      phosphates and lysophosphatidic acid: modulation of cellular activity of
      sphingosine 1-phosphate.
AB  - Sphingolipids have been implicated in the regulation of cell growth,
      differentiation, and programmed cell death. Sphingosine 1-phosphate (SPP) has
      recently emerged as an important lipid messenger and a ligand for the endothelial
      differentiation gene receptor family of proteins through which it mediates its
      biologic effects. Recent studies in Saccharomyces cerevisiae in our laboratory
      implicated the yeast oligomycin resistance gene (YOR1), a member of the ATP
      binding cassette family of proteins, in the transport of SPP. The cystic fibrosis
      transmembrane regulator is a unique member of the ATP binding cassette
      transporter family and has high homology with YOR1. We therefore set out to
      investigate if this member of the family can regulate SPP transport. We
      demonstrate that C127/cystic fibrosis transmembrane regulator (CFTR) cells,
      expressing wild type CFTR, exhibited significantly higher uptake of sphingosine 1
      phosphate than either cells expressing a mutant CFTR C127/DeltaF508 or C127/mock
      transfected cells. This effect was specific, dose-dependent, and competed off by
      dihydrosphingosine 1-phosphate and lysophosphatidic acid. There was no difference
      in uptake of sphingosine, C(16)-ceramide, sphingomyelin, lysophingomyelin,
      phosphatidylcholine, lysophosphatidylcholine, or phosphatidic acid among the
      different cell lines. Pretreatment with forskolin or isobutylmethylxanthine to
      stimulate cAMP did not affect the uptake in any of the cell lines. Moreover, we
      found that mitogen-activated protein kinase activation by SPP was less responsive
      in C127/CFTR as compared with C127/mock-transfected cells, suggesting that uptake
      of SPP by CFTR may divert it from interacting with its cell surface receptors and
      attenuate signaling functions. Taken together, these data implicate CFTR in
      uptake of SPP and the related phosphorylated lipids dihydrosphingosine 1
      phosphate and lysophosphatidic acid. This uptake influences the availability of
      SPP to modulate biologic activity via endothelial differentiation gene receptors.
      These studies may have important implications to cystic fibrosis.

PMID- 11443136
TI  - Novel mechanism of hydrolysis of therapeutic beta-lactams by Stenotrophomonas
      maltophilia L1 metallo-beta-lactamase.
AB  - Stopped-flow tryptophan fluorescence under single turnover and pseudo-first-order
      conditions has been used to investigate the kinetic mechanism of beta-lactam
      hydrolysis by the Stenotrophomonas maltophilia L1 metallo-beta-lactamase. For the
      cephalosporin substrates nitrocefin and cefaclor and the carbapenem meropenem, a
      substantial quench of fluorescence is observed on association of substrate with
      enzyme. We have assigned this to a rearrangement event subsequent to formation of
      an initial collision complex. For the colorimetric compound nitrocefin, decay of
      this dark inter- mediate represents the overall rate-determining step for the
      reaction and is equivalent to decay of a previously observed state in which the
      beta-lactam amide bond has already been cleaved. For both cefaclor and meropenem,
      the rate-determining step for hydrolysis is loss of a second, less quenched
      state, in which, however, the beta-lactam amide bond remains intact. We suggest,
      therefore, that the mechanism of hydrolysis of nitrocefin by binuclear metallo
      beta-lactamases may be atypical and that cleavage of the beta-lactam amide bond
      is the rate-determining step for breakdown of the majority of beta-lactam
      substrates by the L1 enzyme.

PMID- 11443137
TI  - Tumor necrosis factor-alpha-induced adipose-related protein (TIARP), a cell
      surface protein that is highly induced by tumor necrosis factor-alpha and adipose
      conversion.
AB  - Tumor necrosis factor-alpha (TNF alpha) is involved in the physiological and
      biological abnormalities found in two opposite metabolic situations: cachexia and
      obesity. In an attempt to identify novel genes and proteins that could mediate
      the effects of TNFalpha on adipocyte metabolism and development, we have used a
      differential display technique comparing 3T3-L1 cells exposed or not to the
      cytokine. We have isolated a novel adipose cDNA encoding a TNF alpha-inducible
      470-amino acid protein termed TIARP, with six putative transmembrane regions
      flanked by a large amino-terminal and a short carboxyl-terminal domain, a
      structure reminiscent of channel and transporter proteins. Commitment into the
      differentiation process is required for cytokine responsiveness. The
      differentiation process per se is accompanied by a sharp emergence of TIARP mRNA
      transcripts, in parallel with the expression of the protein at the plasma
      membrane. Transcripts are present at high levels in white and brown adipose
      tissues, and are also detectable in liver, kidney, heart, and skeletal muscle.
      Whereas the biological function of TIARP is presently unknown, its pattern of
      expression during adipose conversion and in response to TNF alpha exposure as a
      transmembrane protein mainly located at the cell surface suggest that TIARP might
      participate in adipocyte development and metabolism and mediate some TNF alpha
      effects on the fat cell as a channel or a transporter.

PMID- 11443138
TI  - A novel method to determine the topology of peroxisomal membrane proteins in vivo
      using the tobacco etch virus protease.
AB  - Most proteins essential for the biogenesis of peroxisomes (peroxins) that are
      identified to date are associated with or are integral components of the
      peroxisomal membrane. A prerequisite in elucidating their function is to
      determine their topology in the membrane. We have developed a novel tool to
      analyze the topology of peroxisomal membrane proteins in the yeast Hansenula
      polymorpha in vivo using the 27-kDa NIa protease subunit from the tobacco etch
      virus (TEVp). TEVp specifically cleaves peptides containing the consensus
      sequence, EXXYXQ downward arrowS (tev). We show that cytosolic TEVp and
      peroxisomal TEVp.SKL are selectively active on soluble cytosolic and peroxisomal
      tev-containing proteins in vivo, respectively, without affecting the viability of
      the yeast cells. The tev sequence was introduced in between the primary sequence
      of the peroxisomal membrane proteins Pex3p or Pex10p and the reporter protein
      enhanced green fluorescent protein (eGFP). Co-synthesis of these functional tev
      GFP tagged proteins with either cytosolic TEVp or peroxisomal TEVp.SKL revealed
      that the C termini of Pex3p and Pex10p are exposed to the cytosol. Additional
      applications of the TEV protease to study peroxisome biogenesis are discussed.

PMID- 11443139
TI  - Essential role of the conformational flexibility of helices 1 and 5 on the lipid
      binding activity of apolipophorin-III.
AB  - It has been recently postulated that the conformational flexibility of helices 1
      and 5 of Locusta migratoria apoLp-III could play an important role in early steps
      of binding of this apolipoprotein to a lipid surface (Soulages, J. L., and
      Arrese, E. L. (2000) J. Biol. Chem. 275, 17501-17509). To test this model, we
      have designed a double Cys mutant in which a disulfide bond linking helices 1 and
      5 could be formed, resulting in an apolipoprotein with reduced conformational
      flexibility of its N- and C-terminal helices. Substitution of Thr(18) and
      Ala(147) by Cys residues provided a protein that under nonreducing conditions was
      fully oxidized. The far-UV CD spectra of this mutant in the reduced and oxidized
      states indicated that their secondary structures were identical to the structure
      of the wild type recombinant apoLp-III, which contains no Cys residues. Near-UV
      CD studies confirmed the formation of a disulfide bond and the absence of
      structural perturbations. The lipid binding activity of the reduced mutant, as
      determined by its ability to form discoidal lipoproteins, was nearly identical to
      that of the wild type protein. Contrarily, the disulfide form of the mutant was
      not able to form discoidal lipoproteins with liposomes of either
      dimirystoylphosphatidylcholine or dimyristoylphosphatidylglycerol. It is
      concluded that the separation of the helices 1 and 5 constitutes one of the key
      steps along the complex pathway for the formation of the final apolipoprotein
      lipid-bound state. It is inferred that the conformational flexibility of helices
      1 and 5 is a key property of apoLp-III, allowing the exposure of hydrophobic
      protein regions and the interaction of the hydrophobic faces of the amphipathic
      alpha-helices with the lipoprotein lipid surface.

PMID- 11443140
TI  - Kruppel-like factors: three fingers in many pies.

PMID- 11443143
TI  - Clinical review 130: Addison's disease 2001.
AB  - Whereas it is now more than 150 yr since T. Addison first described the clinical
      and pathological features of adrenal failure (1 ), the disease remains
      underdiagnosed, leading to unnecessary morbidity and mortality. Over the past
      decade, there have been important advances in elucidating the pathogeneses and
      underlying genetics of the individual forms of the disease. This review
      emphasizes the multiple etiologies and the diagnostic steps to be taken with
      consideration to age at onset and gender and summarizes new genetic insights in
      the disease.

PMID- 11443144
TI  - Clinical review 131: Gene therapy for thyroid cancer: where do we stand?

PMID- 11443145
TI  - Acromegaly and cancer: not a problem?

PMID- 11443146
TI  - Clinical perspective: acromegaly and cancer: a problem.

PMID- 11443147
TI  - Endocrinology resources on the internet.

PMID- 11443148
TI  - Polycystic ovarian syndrome--relationship to epilepsy and antiepileptic drug
      therapy.

PMID- 11443149
TI  - Characterization of reproductive endocrine disorders in women with epilepsy.
AB  - An increased frequency of reproductive endocrine disorders has been reported in
      women with epilepsy. A possible role of the seizure disorder or, alternatively,
      of the use of antiepileptic drugs (AEDs) has been suggested as the pathogenic
      mechanism. The aim of the present study was to assess the frequency of
      reproductive endocrine disorders in a series of women with epilepsy, examining
      the possible relationships of these disturbances with different epilepsy
      syndromes and AED treatment. Fifty epileptic women, all of reproductive age and
      none pubertal, pregnant, or lactating, were submitted to clinical
      endocrinological evaluation, hormonal assessment, and ovarian ultrasonography.
      Subjects with abnormal findings in this preliminary study underwent additional
      evaluations. Reproductive endocrine disorders were diagnosed in 16 (32%),
      consisting of polycystic ovary syndrome in 13, hypothalamic amenorrhea in 2, and
      luteal phase deficiency in 1. There was no significant association of these
      disturbances with epilepsy type or AED treatment. Patients with reproductive
      endocrine disorders often showed delayed ovulation with shortened luteal phase.
      The results of this study suggest that the prevalence of disordered ovulation, in
      particular polycystic ovary syndrome, is increased in epilepsy, independent of
      antiepileptic medications or type of seizure disorder.

PMID- 11443151
TI  - Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal
      hyperplasia in five middle European countries.
AB  - Despite the fact that congenital adrenal hyperplasia (CAH) is one of the most
      common inborn endocrine disorders, some patients are not identified, or may even
      die, in an acute salt-losing crisis. In a retrospective study covering the last
      30 yr, we examined the time elapsing before diagnosis of CAH patients, in 5
      Middle European countries, and the mortality rate in diagnosed patients and their
      siblings during childhood; we also attempted to estimate how many patients are
      not diagnosed clinically each year. Basic and follow-up clinical data and the
      family histories of 484 patients with classical forms of CAH diagnosed between
      1969 and 1998 were collected and recorded in 5 Middle European countries. The sex
      ratio, time elapsing before diagnosis, and mortality among siblings and patients
      were calculated, and the number of undiagnosed patients was estimated. We found
      significantly fewer genetic males (43.0%) than females (57.0%) among 484 classic
      CAH patients, and the percentage of diagnosed boys did not increase with time;
      64.7% of them suffered from the salt-wasting (SW) form, and 35.3% from the simple
      virilizing (SV) form, of the disease. The diagnosis of CAH was established
      significantly later in males than in females in both forms [SW: 26 vs. 13 days
      (median), P < 0.0001; SV: 5.0 vs. 2.8 yr, P = 0.03]. Infant mortality in the
      general population was significantly lower than in either siblings (1.8% vs.
      7.0%; P < 0.0001) or in SW (2.29% vs. 11.3%; P < 0.0001). According to our
      calculations, by our current praxis of clinical ascertainment, 2-2.5 SW and up to
      5 SV stay undiagnosed, out of 40 expected CAH patients per year in the countries
      investigated. Both clinical detection and treatment of CAH patients, at least in
      males, were insufficient in the five Middle European countries examined during
      the last 30 yr. Neonatal mass screening and/or greater awareness of the medical
      community are discussed as ways of improving the efficacy of CAH management. Our
      experience may be applicable to other countries with similar health care systems.

PMID- 11443152
TI  - If gonadotropin-releasing hormone plus growth hormone (GH) really improves growth
      outcomes in short non-GH-deficient children, then what?

PMID- 11443153
TI  - A randomized controlled trial of three years growth hormone and gonadotropin
      releasing hormone agonist treatment in children with idiopathic short stature and
      intrauterine growth retardation.
AB  - We assessed the effectiveness and safety of 3 yr combined GH and GnRH agonist
      (GnRHa) treatment in a randomized controlled study in children with idiopathic
      short stature (ISS) or intrauterine growth retardation (IUGR). Gonadal
      suppression, GH reserve, and adrenal development were assessed by hormone
      measurements in both treated children and controls during the study period.
      Thirty-six short children, 24 girls (16 ISS/8 IUGR) and 12 boys (8 ISS/4 IUGR),
      with a height SD score of -2 SD or less in early puberty (girls, B2-3; boys, G2
      3), were randomly assigned to treatment (n = 18) with GH (genotropin 4 IU/m(2).
      day) and GnRHa (triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the
      start of the study mean (SD) age was 11.4 (0.56) or 12.2 (1.12) yr whereas bone
      age was 10.7 (0.87) or 10.9 (0.63) yrs in girls and boys, respectively. During 3
      yr of study height SD score for chronological age did not change in both treated
      children and controls, whereas a decreased rate of bone maturation after
      treatment was observed [mean (SD) 0.55 (0.21) 'yr'/yr vs. 1.15 (0.37) 'yr'/yr in
      controls, P < 0.001, girls and boys together]. Height SD score for bone age and
      predicted adult height increased significantly after 3 yr of treatment; compared
      with controls the predicted adult height gain was 8.0 cm in girls and 10.4 cm in
      boys. Furthermore, the ratio between sitting height/height SD score decreased
      significantly in treated children, whereas body mass index was not influenced by
      treatment. Puberty was effectively arrested in the treated children, as was
      confirmed by physical examination and prepubertal testosterone and estradiol
      levels. GH-dependent hormones including serum insulin-like growth factor I and
      II, carboxy terminal propeptide of type I collagen, amino terminal propeptide of
      type III collagen, alkaline phosphatase, and osteocalcin were not different
      between treated children and controls during the study period. Thus, a GH dose of
      4 IU/m(2) seems adequate for stabilization of the GH reserve and growth in these
      GnRHa-treated children. We conclude that 3 yr treatment with GnRHa was effective
      in suppressing pubertal development and skeletal maturation, whereas the addition
      of GH preserved growth velocity during treatment. This resulted in a considerable
      gain in predicted adult height, without demonstrable side effects. Final height
      results will provide the definite answer on the effectiveness of this combined
      treatment.

PMID- 11443154
TI  - Somatostatin receptor-specific analogs: effects on cell proliferation and growth
      hormone secretion in human somatotroph tumors.
AB  - Somatostatin (SST) acts through a family of seven transmembrane domain G protein
      coupled receptors to inhibit hormone secretion and cell proliferation in a
      variety of neuroendocrine tissues. In normal and neoplastic human pituitary
      somatotroph cells, SST-specific receptor types (SSTR) 1, 2, 3, and 5 are
      prevalently expressed, and SST and its analogs have been shown to inhibit GH
      secretion. However, in somatotroph adenomas, little is known regarding: 1)
      effects of SST and its analogs on pituitary tumor proliferation; 2) the
      relationship between the effects of SST analogs on GH secretion and tumor cell
      proliferation; and 3) whether SSTR expression predicts the antiproliferative
      effects of SST analogs in human somatotroph tumors. We investigated the effects
      of SST-14, lanreotide, and SSTR 2 (BIM-23190) and SSTR 5 (BIM-23268) specific
      analogs in 18 somatotroph pituitary adenomas in primary culture. Our results
      showed that cell proliferation was significantly inhibited by SST-14, lanreotide,
      BIM-23190, and BIM-23268 in 4, 7, 3, and 4 tumors, respectively (range of
      proliferation suppression 5-60%; median, 16%). Tumors that were responsive to
      SSTR 2- and 5-specific analogs were also responsive to lanreotide. SST-14
      inhibited GH secretion in 8 of 13 tumors; lanreotide, BIM-23190, and BIM-23268
      inhibited GH secretion in six tumors each (range of GH secretion inhibition 23
      43%; median 33%). SSTR 2 and 5 messenger RNA was expressed in all tumors
      investigated, whereas SSTR 1 and 3 messenger RNA was expressed in 11 and 12
      tumors, respectively. We observed a dissociation between the in vitro effects of
      SST-14 or lanreotide on tumor cell proliferation and the effects on GH secretion
      in human somatotroph tumors. Although differences in receptor concentration and
      the presence of other SST receptor subtypes may play a role, the presence of SSTR
      2 and/or 5 did not have a predictive value. These data suggest that inhibition of
      cell proliferation occurs independently of effects on GH secretory pathways.
      Further studies are needed to clarify the mechanism of SST induced
      antiproliferative effects.

PMID- 11443155
TI  - Serum leptin, gonadotropin, and testosterone concentrations in male patients with
      anorexia nervosa during weight gain.
AB  - Amenorrhea in female patients with anorexia nervosa is associated with low leptin
      secretion, thus suggesting a causal link. In an attempt to address the hypothesis
      that leptin also influences the hypothalamo-pituitary-gonadal function in males,
      we studied three male patients with acute anorexia nervosa longitudinally. Serum
      levels of leptin, LH, FSH, testosterone, and SHBG were measured on a biweekly
      basis during weight gain. Leptin levels at low body mass index values were below
      the 5th percentile. During weight gain, leptin levels reached or surpassed the
      95th percentile. The temporal dynamics of body mass index and fat mass were
      closely related to those of leptin concentrations in serum. Leptin increments
      were paralleled by increments of gonadotropins, testosterone, and the free
      androgen index (FAI). In each of the patients, serum concentrations of leptin
      were positively correlated with those of testosterone (P = 0.0001, P = 0.01, P =
      0.07, respectively) and FAI (P = 0.0001, P = 0.0001, P = 0.09, respectively). In
      addition, in the combined data set of all patients changes of leptin over time
      were positively correlated with changes in LH (P = 0.01), FSH (P = 0.0001),
      testosterone (P = 0.002), and FAI (P = 0.002). In conclusion, these data suggest
      that leptin might also play an important role in the regulation of the
      hypothalamo-pituitary-gonadal axis and fertility in underweight males as has
      previously been shown in underweight females.

PMID- 11443156
TI  - Modulation of cortisol metabolism by the growth hormone receptor antagonist
      pegvisomant in patients with acromegaly.
AB  - Pegvisomant is a GH receptor antagonist and highly efficacious new treatment for
      acromegaly. The two isoenzymes of 11beta-hydroxysteroid dehydrogenase are
      responsible for the interconversion of cortisol and its inactive metabolite
      cortisone. We demonstrated previously that the type I isoform, which is
      principally responsible for conversion of cortisone to cortisol, is partially
      inhibited by GH. The net activity of the enzyme can be measured by analysis of
      the urinary ratio of 11-hydroxy/11-oxo cortisol metabolites or of the urinary
      ratio of tetrahydrocortisol/tetrahydrocortisone [(tetrahydrocortisol + 5alpha
      tetrahydrocortisol)/tetrahydrocortisone]. We studied the influence of pegvisomant
      on cortisol metabolism in patients with active acromegaly. Seven patients (four
      women and three men; median age, 58 yr; range, 39-72) were studied at baseline
      and again after a mean of 46 weeks of treatment. The mean insulin-like growth
      factor I (IGF-I) level at baseline fell from 939.7 +/- 271.1 to 346.9 +/- 379.0
      ng/mL on 20 mg/day pegvisomant. The 11-hydroxy/11-oxo ratio increased from a
      pretreatment mean value of 0.61 +/- 0.18 to 0.88 +/- 0.20 (P < 0.02) and when the
      six patients in whom serum IGF-I normalized were considered separately, the
      change was from 0.62 +/- 0.19 to 0.90 +/- 0.21 (P < 0.04). The
      tetrahydrocortisols/tetrahydrocortisone ratio increased from a pretreatment mean
      value of 0.64 +/- 0.21 to 0.98 +/- 0.26 (P < 0.02) and in the six patients in
      whom serum IGF-I normalized, the ratio rose from 0.66 +/- 0.23 to 1.01 +/- 0.26
      (P < 0.04). These data 1) indicate that blockade of GH action with pegvisomant in
      patients with acromegaly is associated with reversal of the inhibition of 11beta
      hydroxysteroid dehydrogenase and correction of cortisol metabolism, and 2)
      suggest that in active acromegaly, cortisol clearance is accelerated and that
      this is reversed by successful treatment. This is further evidence of the
      efficacy of pegvisomant in the management of acromegaly and has important
      implications for determining optimum glucocorticoid replacement.

PMID- 11443157
TI  - Evaluation of the hypothalamic-pituitary-adrenal axis in children with leukemia
      before and after 6 weeks of high-dose glucocorticoid therapy.
AB  - Among the adverse effects arising from chronic high-dose glucocorticoid
      treatment, adrenal insufficiency secondary to suppression of the hypothalamic
      pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced
      adrenal suppression is related to the duration of therapy, type of steroid used
      and dosage, and schedule of glucocorticoid administration. To evaluate the
      suppression and recovery time of the HPA axis in children with acute leukemia, we
      performed the ovine CRH (oCRH) stimulation test in 15 patients, who were given
      high doses of dexamethasone as part of their induction chemotherapy for 42 days.
      The oCRH tests were performed before, and 7 and 14 days after, discontinuation of
      the glucocorticoid. The ACTH levels were not significantly different among the 3
      tests. The cortisol levels, however, were significantly (albeit mildly) lower,
      both basally and after oCRH, 1 and 2 weeks post treatment than before therapy.
      Six patients had cortisol values that remained suppressed 2 weeks after
      discontinuation of therapy. One of these patients had manifestations of mild
      adrenal insufficiency, 6-8 days after discontinuation of therapy, but required no
      glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of
      6 weeks of high-dose dexamethasone administration, the HPA axis of patients with
      acute leukemia is mildly suppressed but infrequently associated with clinical
      manifestations of adrenal insufficiency. This may indicate that major stress,
      when concurrent with glucocorticoid treatment, may prevent clinically significant
      adrenal suppression.

PMID- 11443158
TI  - Elevated plasma level of lipotropin revealing an occult carcinoid tumor with
      normal plasma adrenocorticotropin.
AB  - The increases in the level of plasma lipotropin (LPH) and in the LPH/ACTH ratio
      are considered diagnostic tools in ectopic ACTH syndrome. However, plasma ACTH is
      also elevated in this syndrome. We report a case of a small carcinoid tumor with
      an increase in both ACTH and LPH in plasma before surgery. Eight months after the
      tumoral resection, plasma LPH alone was increased again, whereas plasma ACTH and
      plasma and urinary cortisol remained normal in this apparently cured patient.
      This repeated abnormality was the only available feature that allowed successful
      removal of the occult tumoral residue.

PMID- 11443159
TI  - Usefulness of different biochemical markers of the insulin-like growth factor
      (IGF) family in diagnosing growth hormone excess and deficiency in adults.
AB  - The diagnostic approach to acromegaly and GH deficiency frequently includes
      measurement of several components of the insulin-like growth factor (IGF) system.
      IGF-I levels are reported to be good predictors of active and cured acromegaly,
      but are commonly found within the normal age-adjusted range in adult GH-deficient
      (GHD) patients. Circulating concentrations of IGF-binding protein-3 (IGFBP-3),
      acid-labile subunit (ALS), and free IGF-I reflect the GH secretory status, but
      their diagnostic accuracy is still debated. In this study serum levels of total
      and free IGF-I, IGFBP-3, ALS, and IGFBP-3-IGF-I and IGFBP-3-ALS complexes were
      determined in patients previously diagnosed with active (n = 67) or inactive (n =
      16) acromegaly and adult GHD (n = 34) and compared with results obtained in 58
      healthy controls. In healthy subjects, IGF-I, IGFBP-3, ALS, and both IGFBP-3
      complexes declined with age; a correlation was found between IGF-I and IGFBP-3 (r
      = 0.59; P < 0.001), ALS (r = 0.67; P < 0.001), and free IGF-I (r = 0.40; P <
      0.05). Active acromegalic patients showed a significant increase in all
      parameters tested. IGF-I concentrations were above +2 SD in 100% of patients,
      whereas slightly lower sensitivities were shown for IGFBP-3 (85%), ALS (88%), and
      free IGF-I (94%). In this group, IGF-I exhibited a slightly higher correlation
      with IGFBP-3 (r = 0.83; P < 0.001) than with ALS levels (r = 0.78; P < 0.001). In
      cured acromegalic patients, we observed the normalization of all parameters but
      free IGF-I levels. Adult GHD patients showed a significant reduction of all
      hormones. Unlike active acromegalic patients, all parameters had only a modest
      sensitivity in GHD; suppression below -2 SD was observed in 41% of GHD patients
      for IGF-I, 47% for IGFBP-3, 32% for ALS, and 35% for free IGF-I measurements.
      Previous radiotherapy and GH peak response below 3 microg/L were associated with
      significantly lower IGF-I, IGFBP-3, and ALS levels. IGF-I levels were
      significantly correlated to ALS (r = 0.68; P < 0.001) and IGFBP-3 (r = 0.64; P <
      0.001) as well as with free IGF-I (r = 0.67; P < 0.001) levels. By multiple
      regression analysis, the number of anterior pituitary hormones impaired was the
      most predictive indicator of IGF-I, IGFBP-3, and free IGF-I levels in GHD
      patients; conversely, the GH peak response better anticipated ALS concentrations.
      The pattern of IGFBP-3 complexes paralleled previous hormonal findings. In active
      acromegalic patients, IGFBP-3-IGF-I levels were 5.4-fold higher than in controls
      and were above +2 SD in 95% of patients, whereas IGFBP-3-ALS levels were elevated
      in 15% of cases. On the other hand, both IGFBP-3 complexes were able to predict
      GHD in only a minority of cases. Taken together, these data support the
      diagnostic role of IGF-I in acromegaly and suggest that free IGF-I and the IGFBP
      3-IGF-I complex can assist diagnostic strategies in this condition. All markers
      are of limited predictive value in adult GHD, as hormonal values are commonly
      found within the normal limits. In these patients, low IGFBP-3 and IGF-I
      concentrations can add further clinical information on the residual GH activity.

PMID- 11443160
TI  - Normal pituitary hypertrophy as a frequent cause of pituitary incidentaloma: a
      follow-up study.
AB  - Enlargement of the pituitary gland is a frequent cause of incidentaloma and of
      referrals to endocrinologists for hormonal evaluation and therapeutic advice. In
      neuroradiological series, 25-50% of healthy women who are 18-35 yr old have a
      convex superior pituitary contour, but pituitary height exceeds 9 mm in less than
      0.5% of cases. This study was performed to provide thorough clinical and hormonal
      data and long-term endocrinological and imaging follow-up data on subjects with
      incidentally discovered pituitary hypertrophy (height > 9 mm). Seven eugonadal
      nulliparous women, 15-27 yr old, referred between 1989 and 1998 with incidentally
      diagnosed pituitary gland enlargement (height > 9 mm) and a suspected pituitary
      tumor, were studied. At presentation and at yearly intervals, PRL plasma levels
      and corticotropic, somatotropic, and thyrotropic pituitary function were
      measured; and pituitary dimensions and signal on magnetic resonance imaging
      (MRI), before and after iv gadolinium-diethylene-triamine-pentaacetic acid
      injection, were assessed. PRL plasma levels were normal; and corticotropic,
      somatotropic, and thyrotropic pituitary function was considered normal in all
      cases. In all the women, the upper boundary of the pituitary was convex, on MRI,
      and touched the optic chiasm in four cases. The width and anteroposterior
      diameter of the gland were normal. The pituitary itself seemed normal, with a
      homogeneous signal, on plain and dynamic studies with iv contrast injection.
      Despite normal initial hormone values, two women underwent surgery, by the
      transsphenoidal approach, in another center. During surgery, the pituitary seemed
      normal in both cases, with no evidence of tumoral or inflammatory processes.
      Biopsy specimens showed the morphologic characteristics of a normal,
      nonhyperplastic pituitary gland. All seven women were seen at yearly intervals
      for 2-8 yr (median, 4 yr). Clinical and hormonal status remained stable, as did
      the structure and size of pituitary, on serial MRI. No tumor formation occurred,
      supporting the diagnosis of physiologic hypertrophy of the pituitary gland. In
      conclusion, these observations suggest that careful examination of MRI results
      may help to distinguish physiologic pituitary hypertrophy from pituitary tumors
      and infiltrating lesions. The former diagnosis is confirmed by normal baseline
      pituitary function in extensive hormonal tests. Correct identification of such
      patients is important to avoid unnecessary pituitary surgery and costly MRI
      surveillance.

PMID- 11443161
TI  - The effect of antithyroid drug pretreatment on acute changes in thyroid hormone
      levels after (131)I ablation for Graves' disease.
AB  - Acute changes in thyroid hormone levels before and after radioiodine therapy for
      Graves' disease were compared in 42 patients randomized to receive either
      antithyroid drug pretreatment or no pretreatment. Five patients (11.9%),
      including 3 in the pretreatment arm and 2 in the no pretreatment arm experienced
      a late exacerbation of thyrotoxicosis after radioiodine therapy. The majority (19
      of 21, 90.5%) of pretreated patients experienced a transient increase in free
      T(4) and free T(3) after discontinuation of antithyroid drugs, with little
      further elevation after radioiodine therapy. After stopping antithyroid drugs and
      before radioiodine administration, mean serum free T(4) values rose from 14.7 +/-
      6.9 to 21.6 +/- 12.1 pmol/L, representing a 46.9% increase, whereas serum free
      T(3) levels rose from 4.9 +/- 1.7 to 8.1 +/- 6.3 pmol/L, representing a 65.3%
      increase. The average pretreated patient experienced a 52.4% increase [95%
      confidence interval (CI), +26.4% to +78.5%] in free T(4) and a 61.8% increase
      (95% CI, +23.5% to +100.0%) in free T(3). Conversely, the majority (19 of 21,
      90.5%) of nonpretreated patients experienced a rapid decline in thyroid hormone
      levels after radioiodine treatment. Over the 14 days after radioiodine therapy
      mean free T(4) values in nonpretreated patients fell from 85.8 +/- 60.4 to 58.0
      +/- 76.5 pmol/L, representing a 32.4% decrease, whereas mean free T(3) levels
      fell from 16.1 +/- 8.0 to 10.8 +/- 11.1 pmol/L, representing a 32.9% decrease.
      The average nonpretreated patient experienced a 20.6% decrease (95% CI, -47.3% to
      +7.0%) in free T(4) and a 24.3% decrease (95% CI, -1.2% to -47.4%) in free T(3)
      during this time period. Excluding 2 patients with a late exacerbation after
      radioiodine, 19 nonpretreated patients experienced a decrease in mean free T(4)
      values from 76.8 +/- 46.6 to 36.6 +/- 19.8 pmol/L, representing a 52.3% decrease,
      whereas mean free T(3) levels fell from 15.5 +/- 7.7 to 7.8 +/- 3.6 pmol/L,
      representing a 49.7% decrease. The average decrease in free T(4) levels among
      this subgroup of patients was 30.1% (95% CI, -4.6% to -55.6%), whereas the
      average decrease in free T(3) was 34.4% (95% CI, -13.7% to -55.1%). High levels
      of TSH receptor autoantibodies at diagnosis were associated with an acute
      worsening of thyrotoxicosis after stopping antithyroid drug pretreatment. We
      conclude that pretreatment with antithyroid drugs does not protect against
      worsening thyrotoxicosis after radioiodine, but may allow such patients to start
      from a lower baseline level should an aggravation in thyrotoxicosis occur. The
      findings support the recommendation that most patients with Graves' disease do
      not require antithyroid drug pretreatment before receiving radioiodine.

PMID- 11443162
TI  - Lipolysis in African-American children: is it a metabolic risk factor
      predisposing to obesity?
AB  - Rates of obesity and type 2 diabetes are higher in African-American (AA),
      compared with American white (AW), adults and children. It is not known whether
      biologic and/or environmental differences are responsible for this racial
      disparity. We and others have demonstrated that AA children are hyperinsulinemic,
      compared with their AW peers. This investigation tested the hypothesis that
      hyperinsulinemia in AA children is associated with lower rates of lipolysis,
      which could be a risk factor for future obesity. Forty prepubertal children (20
      AA and 20 AW) with comparable body composition (assessed by dual-energy x-ray
      absorptiometry) and visceral adiposity (evaluated with computed tomography scan)
      were studied. Total body lipolysis was measured with [(2)H(5)]glycerol after
      overnight fasting. Basal lipolysis was approximately 40% lower in AA vs. AW
      children, whether the data were expressed for total body (85.7 +/- 8.9 vs. 130.3
      +/- 14.1 micromol/min, P = 0.011) or per-kilogram BW (2.4 +/- 0.2 vs. 3.8 +/- 0.4
      micromol/min.kg, P = 0.002) or per kilogram fat free mass (FFM) (3.3 +/- 0.3 vs.
      5.2 +/- 0.5 micromol/min.kg FFM, P = 0.004), or per kg fat mass (FM) (13.7 +/-
      1.6 vs. 21.3 +/- 3.3 micromol/min.kg FM, P = 0.046). Fasting insulin levels were
      higher in AA children (99.6 +/- 7.8 vs. 77.4 +/- 5.9 pmol/L, P = 0.032).
      Lipolysis correlated positively with fat mass, percent body fat, and abdominal
      fat mass. However, in multiple-regression analysis models after controlling for
      insulin and body composition, race remained a significant contributor to the
      variance in lipolysis. In summary, the present study demonstrates that rates of
      lipolysis are significantly lower in AA children, compared with their white
      peers. This may constitute an early metabolic phenotype that may mediate fat
      trapping and susceptibility to obesity in a specific environmental context of
      energy excess conducive to fat accretion.

PMID- 11443163
TI  - Longitudinal changes of insulin sensitivity in essential hypertension: influence
      of blood pressure control and familial predisposition to hypertension.
AB  - The aim of this study was to evaluate the influence of blood pressure (BP)
      control and familial predisposition to hypertension on longitudinal changes in
      insulin sensitivity in essential hypertension. We evaluated 6 groups of subjects
      twice (basal: before any treatment; 2nd: after at least 18 months): 42
      hypertensives (H) with a family history of hypertension (F+) and 30 H without a
      family history of hypertension (F-) successfully treated with angiotensin
      converting enzyme inhibitors and/or calcium channel blockers (2nd: 24-h BP < or =
      130/80 mm Hg); 22 untreated (UT) HF+ and 18 UTHF- (2nd: 24-h BP >140 and/or 90 mm
      Hg); 18 normotensives F+ and 15 normotensives F-. The parameters evaluated were
      as follows: glucose, insulin, and C-peptide (Cp) response to an oral glucose
      load. Glucose was normal in all of the subjects, similar among the 6 groups, and
      unchanged at the 2nd evaluation. At the basal evaluation insulin and Cp were
      higher and the metabolic clearance rate (MCR) of glucose was lower in the three
      F+ groups compared with the corresponding F- groups. In the 2nd evaluation
      insulin and Cp were reduced and the MCR of glucose increased in THF-, whereas all
      metabolic parameters were unchanged in THF+; in both UT hypertensive groups
      insulin and Cp increased and the MCR of glucose decreased, more so in F+ than in
      F-; in normotensive groups metabolic parameters did not change. A familial
      predisposition to hypertension influences insulin sensitivity changes during
      successful antihypertensive therapy, with an improvement in insulin sensitivity
      in F- and no changes in F+. A persistently high BP has a negative influence on
      insulin sensitivity in F+ and F-; this influence is greater when high BP is
      associated with a familial predisposition to hypertension.

PMID- 11443164
TI  - High levels of antigen-specific islet antibodies predict future beta-cell failure
      in patients with onset of diabetes in adult age.
AB  - It is unclear whether high levels of antigen-specific islet antibodies [GADA
      (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine
      phosphatase-like protein antibodies)] predict beta-cell failure in patients with
      onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the
      diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later
      in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median,
      57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta
      cell failure (undetectable fasting plasma C-peptide) was only present in 4
      patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At
      diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure
      after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5
      percentile of healthy controls) were detected in all 21 (100%) with but also in
      23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a
      higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05).
      With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were
      detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127
      (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA
      levels in IA2-ab-negative patients were associated with progressive but not
      complete beta-cell failure within the study period. Hence, high GADA and/or IA2
      ab levels predict a future complete beta-cell failure, whereas low GADA levels
      predict slowly progressive beta-cell insufficiency.

PMID- 11443165
TI  - Nocturnal application of transdermal estradiol patches produces levels of
      estradiol that mimic those seen at the onset of spontaneous puberty in girls.
AB  - The objective of pubertal induction in children with hypogonadism is to mimic
      spontaneous puberty in terms of physical and psychological development. In a
      clinical observation study, we induced puberty in 15 girls with hyper- or
      hypogonadotropic hypogonadism using low doses of transdermal estradiol patches
      attached only during the night and compared the estradiol concentrations obtained
      with those in healthy girls. Pubertal induction was started between the ages of
      12.3 and 18.1 yr. A transdermal matrix patch of 17beta-estradiol (25 microg/24 h;
      Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1,
      4.2, or 6.2 microg/24 h initially and attached to the buttock. After 4-14 months,
      the dose was increased gradually. Serum 17beta-estradiol concentrations were
      measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results
      show that it is possible to mimic the spontaneous levels as well as the diurnal
      pattern of serum 17beta-estradiol in early puberty, by cutting a transdermal
      17beta-estradiol matrix patch and attaching a part of it, corresponding to 0.08
      0.12 microg estradiol/kg BW, to the buttock nocturnally. In most of the girls,
      breast development occurred within 3-6 months of the start of treatment.

PMID- 11443166
TI  - Effects of an isoflavone-free soy diet on ovarian hormones in premenopausal
      women.
AB  - Soy intakes have been associated with reduced rates of breast cancer in some
      Asian populations. The isoflavones daidzein and genistein and other components of
      soybeans may modulate endocrine function and lead to beneficial health effects.
      This study determined the effects of a soy diet containing minimum amounts of
      isoflavones on circulating levels of ovarian hormones and gonadotropins. Nine
      healthy, regularly cycling women consumed a constant soya-containing diet on a
      metabolic unit starting on day 2 of a menstrual cycle until day 2 of the next
      cycle. The soy diet was calculated to maintain constant body weight and included
      a 36-oz portion of soymilk that provided 334 kilocalories and less than 5 mg/day
      of total isoflavones. The energy distribution of the soy diet was 35.9% fat,
      14.0% protein, and 49.8% carbohydrate whereas the home diets averaged 39% fat,
      16.6% protein, and 42.5% carbohydrate. For the group, the soya diet provided more
      carbohydrate (P = 0.002) and less protein (P = 0.005) than the home diets. Daily
      consumption of the soya diet reduced daily circulating levels of 17beta-estradiol
      over the entire menstrual cycle by 20% (P < 0.01, paired t test, two-tailed) and
      progesterone by 33% (P < 0.0001) compared with levels during the home diet
      period, but had no effect on LH, FSH, or sex hormone-binding globulin. The
      decreases in follicular phase 17beta-estradiol during the soy diet can be
      accounted for by changes in energy intakes, nutrient density, and fiber intake,
      whereas changes in luteal phase 17beta-estradiol were most strongly associated
      with differences in fiber intake. Changes in progesterone levels were most
      strongly associated with changes in protein intake and much less with other
      nutrients. Isoflavones were not detectable in plasma and urine during either the
      soy or home diet periods. These results suggest that at least under the
      conditions of this study, a soy diet with low levels of isoflavones and low
      energy intake from protein can reduce circulating ovarian steroids without
      altering gonadotropins. Our results are consistent with previous studies showing
      decreased ovarian hormone levels and decreased risk of breast cancer in
      populations consuming soya diets and an inverse relationship between animal
      protein intake and breast cancer risk and, therefore, may have implications for
      breast cancer prevention.

PMID- 11443167
TI  - Dietary soy has both beneficial and potentially adverse cardiovascular effects: a
      placebo-controlled study in men and postmenopausal women.
AB  - To address the cardiovascular effects of dietary soy containing phytoestrogens,
      we measured blood pressure (BP), lipids, vascular function (systemic arterial
      compliance and pulse wave velocity), and endothelial function (flow-mediated
      vasodilation) in a randomized, double-blind trial. Two hundred thirteen healthy
      subjects (108 men and 105 postmenopausal women), 50-75 yr old, received either
      soy protein isolate (40 g soy protein, 118 mg isoflavones) or casein placebo for
      3 months. There were 34 withdrawals (16%), with 179 subjects (96 men and 83
      women) completing the protocol. After intervention in the soy group, compared
      with casein placebo, urinary phytoestrogens increased, accompanied by a
      significant fall in BP reflected by the BP model (P < 0.01) encompassing mean
      change (+/-SEM) in systolic (-7.5 +/- 1.2 vs. -3.6 +/- 1.1 mm Hg, P < 0.05),
      diastolic (-4.3 +/- 0.8 vs. -1.9 +/- 0.7 mm Hg, P < 0.05), and mean BP (-5.5 +/-
      1 vs. -0.9 +/- 1 mm Hg, P < 0.008). In the lipid model, soy induced greater
      changes, compared with placebo (P < 0.001). On individual analysis, significant
      contributors included a reduction in the low- to high-density lipoprotein ratio (
      0.33 +/- 0.1 vs. 0.04 +/- 0.1 mmol/L, P < 0.05) and triglycerides (-0.2 +/- 0.05
      vs. -0.01 +/- 0.05 mol/L, P < 0.05) and an increase in Lp(a) lipoprotein (+/- 95%
      confidence interval) [42 (range, 17-67) vs. 4 (range, -22-31) mg/L, P < 0.05],
      whereas total, low-density lipoprotein, and high-density lipoprotein cholesterol
      improved in both groups; but no treatment effect was demonstrated. The arterial
      functional model demonstrated no difference between groups; although again,
      overall function improved in both groups. On individual analysis, peripheral PWV
      (reflecting peripheral vascular resistance) improved with soy (P < 0.01), whereas
      flow-mediated vasodilation (reflecting endothelial function) declined (in males
      only), compared with casein placebo (P < 0.02). No effect of treatment on the
      hypothalamic-pituitary-gonadal axis was noted in males or females. In
      normotensive men and postmenopausal women, soy improved BP and lipids but,
      overall, did not improve vascular function. Potential adverse effects were noted,
      with a decline in endothelial function (in males only) and an increase in Lp(a).
      Further research in hypertensive and hyperlipidemic populations is needed.

PMID- 11443168
TI  - Recommendations for the diagnosis and management of Turner syndrome.
AB  - Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the
      care of affected individuals were published in 1994. In the light of recent
      advances in diagnosis and treatment of TS, an international multidisciplinary
      workshop was convened in March 2000, in Naples, Italy, in conjunction with the
      Fifth International Symposium on Turner Syndrome to update these recommendations.
      The present paper details the outcome from this workshop. The genetics and
      diagnosis of the syndrome are described, and practical treatment guidelines are
      presented.

PMID- 11443169
TI  - Long term outcome in adult males with classic congenital adrenal hyperplasia.
AB  - The effects of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency on final height and fertility were evaluated in 30 affected males,
      aged 17-43 yr. The mean adult height of these patients was 165.64 +/- 8.4 cm
      (mean +/- SD), with a mean SD score of -1.65 +/- 1.2 cm. The difference between
      the mean final height SD score and mean target height SD score was -1.67 +/- 1.0
      cm. All patients had short stature and did not reach their estimated target
      heights. There was no difference in height SD score between the salt-wasting and
      simple virilizing CAH patients. No correlation between the final height and
      degree of hormonal control or bone age advancement was observed. Of the 30
      subjects, 18 had testicular sonograms. Abnormal sonogram findings of testicular
      adrenal rests were present in 9 patients (group 1), whereas sonogram without
      adrenal rests comprised the remaining 9 patients (group 2). In group 1, 8 of 9
      patients and in group 2, 4 of 9 patients were salt-wasters; the remainder were
      simple virilizers. In group 1, 7 of 9 patients had semen analysis, and all were
      judged infertile. Of the 6 patients in group 2 who had semen analysis, 1 was
      azoospermic, and the remainder were normal. During optimal adrenal hormone
      suppression, gonadotropins at baseline and after GnRH stimulation were
      significantly higher in group 1 than in group 2, reflecting the loss of Leydig
      cell function to secrete testosterone. In conclusion, adult males affected with
      CAH due to 21-hydroxylase deficiency do not achieve the height predicted from
      parental heights. The presence of adrenal rests within the testes of adult males
      with classic CAH are more frequent in the salt-wasting form and are associated
      with a higher risk for infertility.

PMID- 11443170
TI  - Additional beneficial effects of alendronate in growth hormone (GH)-deficient
      adults with osteoporosis receiving long-term recombinant human GH replacement
      therapy: a randomized controlled trial.
AB  - We conducted a randomized controlled trial in osteoporotic adult GH-deficient
      (GHD) patients to assess whether additional treatment with a bisphosphonate would
      further favorably influence parameters of bone turnover and bone mineral density
      measurements (BMD). All patients were receiving stable recombinant human (rhGH)
      replacement therapy for 4 yr at the start of the study. Eighteen GHD patients
      with osteoporosis were randomized to continue their rhGH maintenance dose or to
      receive combination therapy with rhGH and alendronate for 12 months. All patients
      were calcium and vitamin replete, and there were no changes in calcium, vitamin
      D, or hormone replacement therapy for the duration of the study. At baseline
      there were no significant differences between the alendronate and the control
      group in parameters of bone turnover, BMD, or prevalence of vertebral fractures.
      Childhood-onset and adult-onset GHD were equally distributed between the groups,
      with no statistical differences in age and gender or other parameters between
      groups. Mean serum osteocalcin, serum bone-specific alkaline phosphatase, and
      urinary N-telopeptide/creatinine ratio were within the normal range at the start
      of the study. In the alendronate group all measured parameters of bone turnover,
      i.e. bone-specific alkaline phosphatase, osteocalcin, and urinary N
      telopeptide/creatinine ratio, significantly decreased after 6 months, with no
      further decrease thereafter. No changes were observed in the control group. In
      the alendronate-treated patients serum bone-specific alkaline phosphatase
      decreased from 10.9 +/- 0.9 to 6.8 +/- 0.7 microg/L at 6 months (P < 0.001),
      serum osteocalcin decreased from 3.9 +/- 0.4 to 1.7 +/- 0.3 microg/L (P < 0.001),
      and the urinary N-telopeptide/creatinine ratio decreased from 27.3 +/- 7.0 to 6.4
      +/- 0.8 nmol/mmol (P = 0.01). In this group, lumbar spine BMD significantly
      increased from baseline by 3.4% at 6 months (P = 0.001) and by 4.4% at 12 months
      (P < 0.001) of treatment, with no further significant increase between 6 and 12
      months (P = 0.217). No changes in lumbar spine BMD were observed in the control
      group. There were no significant changes in femoral neck BMD in either group for
      the duration of the study. No incident vertebral or peripheral fractures were
      documented in either group at the end of the study. In summary, this is the first
      report indicating that treatment with alendronate was able to significantly
      increase BMD at the lumbar spine in GHD patients with osteoporosis receiving
      stable rhGH replacement for 4 yr. This increase was significantly greater in
      alendronate-treated patients than in patients maintained on rhGH. The increase in
      lumbar spine BMD in the alendronate-treated patients was associated with a
      decrease in the measured markers of bone turnover, whereas these markers did not
      change further in the patients maintained on rhGH. This controlled study suggests
      that additional treatment with alendronate in GHD patients with osteoporosis
      receiving stable rhGH replacement therapy is effective in increasing BMD at the
      lumbar spine. Further investigation is required to assess whether rhGH
      replacement alone or combined treatment with rhGH and alendronate is able to
      reduce the increased fracture risk associated with GHD.

PMID- 11443171
TI  - Vitamin D status and redefining serum parathyroid hormone reference range in the
      elderly.
AB  - Subclinical vitamin D insufficiency is characterized by mild secondary
      hyperparathyroidism and enhanced risk of osteoporotic fracture. However, although
      low levels of 25-hydroxyvitamin D (25OHD) are common in otherwise normal elderly
      people, vitamin D status has not generally been taken into account in the
      previously published reference values for serum PTH. We measured fasting morning
      serum (obtained from April through June) PTH, total calcium, albumin, phosphate,
      creatinine, bone markers, and 25OHD in 280 healthy subjects (140 men and 140
      women), aged 60-79 yr. Serum PTH was measured by means of 2 immunoradiometric
      assays, the Allegro intact PTH assay (Nichols Institute Diagnostics) and the new
      CAP assay (Scantibodies Laboratory, Inc.). We found a high prevalence (167 of
      280; 59.6%) of low 25OHD (< or =30 nmol/L) in these otherwise healthy
      individuals. The PTH concentrations (95% confidence interval) obtained in the
      whole group of 280 subjects ranged from 13-64 ng/L for the Allegro assay and from
      10-44 ng/L for the CAP assay. In the subjects with a serum 25OHD concentration
      greater than 30 nmol/L, values for both PTH assays were lower, 10-46 and 9-34
      ng/L for the Allegro and the CAP assays, respectively. By using these values as a
      reference range, approximately 25% of the subjects with a serum 25OHD level of 30
      nmol/L or less had a high serum PTH level (whatever the assay), reflecting
      secondary hyperparathyroidism. This might be missed if the reference PTH values
      are those obtained in the entire group, as is usually done. These results
      strongly suggest that vitamin D status should be taken into account when
      establishing reference values for serum PTH in elderly subjects.

PMID- 11443172
TI  - Pseudohypoparathyroidism Ia and hypercalcitoninemia.
AB  - Pseudohypoparathyroidism Ia (PHP Ia) is characterized by resistance to PTH and
      many other stimuli because of deficiency of stimulatory G protein alpha-subunit.
      To determine the incidence, natural history, and mechanism of C cell dysfunction
      in PHP, calcitonin assays were performed in six patients with PHP Ia and four
      with pseudopseudohypoparathyroidism from three unrelated families. Controls
      included healthy subjects and patients with PHP Ib or hypoparathyroidism. The
      mean basal level of calcitonin was higher in PHP Ia patients than in controls
      (95.3 +/- 112.7 vs. 3.7 +/- 2.4 pg/mL; P = 0.005; n < 10). In PHP Ia patients,
      calcitonin levels rose over the normal range (30 pg/mL) after pentagastrin
      infusion in five patients and remained normal in one. Familial medullary thyroid
      carcinoma was clinically, biologically, and ultrasonographically ruled out over a
      mean follow-up exceeding 3 yr. Genomic screening for RET protooncogene mutations
      failed to reveal any anomaly. The calcitonin infusion test, which induced a
      significant increase in plasma cAMP in controls 30 and 60 min after infusion,
      failed to produce this response in PHP Ia patients, suggesting that the action of
      calcitonin was specifically impaired. PHP Ia may therefore be an independent
      etiology of hypercalcitoninemia and hyperresponsiveness to pentagastrin infusion.

PMID- 11443173
TI  - Novel patterns of gene expression in pituitary adenomas identified by
      complementary deoxyribonucleic acid microarrays and quantitative reverse
      transcription-polymerase chain reaction.
AB  - Pituitary adenomas account for approximately 10% of intracranial tumors, but
      little is known of the oncogenesis of these tumors. The identification of tumor
      specific genes may further elucidate the pathways of tumor formation. We used
      complementary DNA microarrays to examine gene expression profiles in
      nonfunctioning, PRL, GH, and ACTH secreting adenomas, compared with normal
      pituitary. Microarray analysis showed that 128 of 7075 genes examined were
      differentially expressed. We then analyzed three genes with unique expression
      patterns and oncogenic importance by RT-real time quantitative PCR in 37
      pituitaries. Folate receptor gene was significantly overexpressed in
      nonfunctioning adenomas but was significantly underexpressed in PRL and GH
      adenomas, compared with controls and to other tumors. The ornithine decarboxylase
      gene was significantly overexpressed in GH adenomas, compared with other tumor
      subtypes but was significantly underexpressed in ACTH adenomas. C-mer proto
      oncogene tyrosine kinase gene was significantly overexpressed in ACTH adenomas
      but was significantly underexpressed in PRL adenomas. We have shown that at least
      three genes involved in carcinogenesis in other tissues are also aberrantly
      regulated in the major types of pituitary tumors. The evaluation of candidate
      genes that emerge from these experiments provides a rational approach to
      investigate those genes significant in tumorigenesis.

PMID- 11443174
TI  - Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing
      effects on monocyte chemotaxis in endometriosis.
AB  - The peroxisome proliferator-activated receptors (PPARs) alpha and gamma are
      nuclear receptors that play important roles in inflammatory diseases like
      ulcerative colitis and arthritis. In this study, we examined the possible role of
      PPARs in macrophage attraction into the peritoneal cavity of patients with
      endometriosis. We identified PPAR-alpha and -gamma messenger RNA by RT-PCR and
      protein by immunoblotting of lysates of peritoneal macrophages and monocytic U937
      cells. Using immunocytochemistry, we localized PPAR-alpha and -gamma within the
      nuclei of both cell types. Monocyte chemotactic activity of peritoneal fluid from
      patients with endometriosis was quantified in Boyden chambers. Migration of U937
      cells was increased by WY 14643 and reduced by rosiglitazone. Peritoneal fluid
      from patients with endometriosis activated U937 cells transiently transfected
      with a PPAR-alpha/GAL4 luciferase reporter. By contrast, peritoneal fluid did not
      cause significant activation of PPAR-gamma/GAL4 constructs. The U937 cells
      transiently transfected with a PPAR response element luciferase reporter showed
      disease stage-dependent up-regulation when treated with peritoneal fluid from
      patients with endometriosis. Treatment with peritoneal fluid from healthy
      controls down-regulated PPAR response element transactivation. We conclude that
      peritoneal fluid of endometriosis patients contains activators of PPAR-alpha that
      stimulate macrophage chemotaxis. Inhibitors of PPAR-alpha or activators of PPAR
      gamma could be developed for the treatment of inflammation associated with
      endometriosis.

PMID- 11443175
TI  - Phosphatidyl-inositol-3 kinase-independent insulin action pathway(s) in the human
      ovary.
AB  - Hyperandrogenism observed in women with a variety of insulin-resistant states is
      thought to be due to a stimulatory effect of insulin on ovarian steroid hormone
      production. However, it is not known what mechanisms could allow the ovary to
      remain sensitive to insulin while classical target organs for insulin action
      (liver, fat, and muscle) exhibit insulin resistance. One hypothesis proposed to
      explain this paradox suggests that a postbinding divergence of insulin receptor
      signaling occurs in the ovary and that signaling pathways for steroid hormone
      synthesis and other ovarian effects of insulin may be distinct from classical
      glucose signaling pathways. We now report that activation of phosphatidyl
      inositol-3 (PI-3) kinase, which is crucial for glucose transport, is not
      necessary for the insulin-induced stimulation of progesterone production or for
      the insulin-induced inhibition of insulin-like growth factor binding protein 1
      (IGFBP-1) production in cultured human ovarian cells. Human granulosa cells
      obtained during in vitro fertilization procedures were cultured with 10, 10(2),
      10(3), or 10(4) ng/mL insulin with or without preincubation with 100 nM
      wortmannin, a specific irreversible inhibitor of PI-3 kinase. IGFBP-1
      concentration in the conditioned medium was measured using immunoradiometric
      assay or by Western blot analysis. Progesterone concentration was measured using
      RIA. Additional studies were carried out in cultures of human ovarian cells
      prepared from homogenized whole ovarian tissue of a woman with a family history
      of breast cancer and a mutation of BRCA-1 gene who underwent bilateral
      oophorectomy. These cells were cultured with 10(3) ng/mL insulin with or without
      preincubation with 100 nM wortmannin. Two-way ANOVA was used to compare mean
      values of IGFBP-1 and progesterone according to insulin dose and the use of
      wortmannin. In cultured granulosa cell medium, progesterone production was
      stimulated by insulin in a dose-related manner up to 175% of control (P <
      0.0001). In tissue culture medium from ovarian cells obtained from a patient with
      BRCA-gene mutation, concentration of progesterone in the tissue culture medium
      increased from 2.5 +/- 0.2 ng/mL for control to 5.4 +/- 0.3 ng/mL for cells
      incubated with insulin (P < 0.001). IGFBP-1 production in tissue culture medium
      from human granulosa cells was inhibited by insulin to the nadir of 45% of
      control (P < 0.0001). Preincubation with wortmannin, despite complete inhibition
      of PI-3 kinase in both cell systems confirmed by Western blot analysis, failed to
      significantly alter these results. We conclude that inhibition of PI-3 kinase by
      wortmannin fails to abolish stimulatory effect of insulin on progesterone
      production or inhibitory effect of insulin on IGFBP-1 production in cultured
      human ovarian cells. These findings suggest that activation of PI-3 kinase, an
      enzyme crucial for insulin-stimulated glucose transport, is not necessary for the
      above effects of insulin in the ovary. These data provide evidence for the
      presence of PI-3 kinase-independent insulin signaling pathway(s) in human ovarian
      cells.

PMID- 11443176
TI  - Continuation of growth hormone (GH) substitution during fasting in GH-deficient
      patients decreases urea excretion and conserves protein synthesis.
AB  - The consequences of GH deficiency during conditions in which endogenous GH
      release is acutely stimulated are largely unknown. Short-term fasting constitutes
      a robust GH stimulus, but the metabolic significance of GH during fasting is
      uncertain. To address both of these issues, we therefore evaluated the effect of
      GH on substrate metabolism during fasting in adults with GH deficiency. Seven
      hypopituitary GH-deficient patients were each studied twice during a 40-h fast:
      once with GH replacement continued and once with GH discontinued during the fast.
      After 40 h of fasting, protein synthesis and turnover were higher with than
      without GH replacement [phenylalanine incorporation (micromol/kg fat free
      mass/h): 36.6 +/- 1.2 (GH) vs. 32.8 +/- 1.4, P < 0.05; phenylalanine flux
      (micromol/kg fat free mass/h): 41.3 +/- 1.0 (GH) vs. 38.0 +/- 1.8, P < 0.05].
      During continued GH replacement, urea excretion decreased during nighttime [urea
      excretion (mmol/24 h): 269 +/- 51 (GH) vs. 390 +/- 69, P < 0.05], and a
      significant decline in urea-N synthesis rate was found [urea-N synthesis rate
      (mmol/h): 14.7 +/- 1.6 (GH) vs. 21.1 +/- 2.2, P < 0.01]. GH replacement was
      associated with increased lipid oxidation [lipid oxidation (mg/kg per min): 0.91
      +/- 0.07 (GH) vs. 0.70 +/- 0.03, P < 0.05]. Finally, continuation of GH induced
      moderate elevations in plasma glucose levels without significant changes in total
      glucose turnover or oxidation. In summary, continued GH substitution during
      fasting conserves nitrogen, which involves stimulation or maintenance of protein
      synthesis. Our data support the importance of GH replacement in hypopituitary
      adults.

PMID- 11443177
TI  - Troglitazone reduces the expression of PPARgamma while stimulating that of
      PPARalpha in mononuclear cells in obese subjects.
AB  - We have recently demonstrated that troglitazone exerts an anti-inflammatory
      effect in the insulin resistant obese in vivo in parallel with its insulin
      sensitizing effect. Because these effects are thought to be mediated through
      peroxisome proliferator-activated receptors alpha and gamma (PPARalpha and
      PPARgamma), we have now examined the possibility that troglitazone may modulate
      the expression of PPARalpha and PPARgamma. Seven obese hyperinsulinemic subjects
      were administered 400 mg troglitazone daily for 4 weeks. Fasting blood samples
      were obtained before and during troglitazone therapy at 1, 2, and 4 weeks.
      Fasting insulin concentrations fell at week 1 and persisted at lower levels till
      4 weeks. PPARgamma expression fell significantly at week 1 and fell further at
      weeks 2 and 4. In contrast, PPARalpha expression increased significantly at week
      2 and further at week 4. 9- and 13-hydroxyoctadecanoic acid, products of linoleic
      acid peroxidation and agonists of PPARgamma, decreased during troglitazone
      therapy. We conclude that troglitazone, an agonist for both PPARalpha and
      PPARgamma, has significant but dramatically opposite effects on PPARalpha and
      PPARgamma. These effects may be relevant to its insulin sensitizing and anti
      inflammatory effects.

PMID- 11443178
TI  - Postprandial remnant-like lipoproteins in hypertriglyceridemia.
AB  - It has been proposed that remnants of chylomicrons and very-low-density
      lipoproteins (VLDL) are atherogenic. We have used an immunochemical method to
      isolate remnant-like particles (RLP) and measured them in terms of their
      cholesterol and triglycerides (TG). RLP consist of apoB-48-containing
      triglyceride-rich lipoproteins and remnant-like VLDL containing apoB-100. The
      study aim was to look for information from postprandial RLP data that could not
      be known from other markers of triglyceride-rich lipoproteins and fasting TG and
      RLP data alone. A total of 41 subjects were studied. Eight subjects had
      hypertriglyceridemia (HTG) and low high-density lipoprotein (HDL), 14 had
      combined hyperlipidemia (CH), 5 had the apo E2/2 genotype receiving gemfibrozil,
      10 were normolipidemic (NL) controls, and 4 had hypercholesterolemia. As a whole
      group, there was correlation among 1) fasting TG, RLP cholesterol (RLP-C), and
      RLP-TG but not VLDL apo B100, VLDL apo B48 and their respective postprandial
      responses measured as incremental area under the curve (IAUC), 2) fasting TG and
      postprandial IAUC of RLP-C and RLP-TG, 3) RLP-C IAUC, RLP-TG IAUC, and TG IAUC,
      retinyl palmitate (RP) IAUC, and VLDL apo B48 IAUC but not VLDL apo B100 IAUC.
      The HTG/low HDL-C and CH groups had higher IAUC for RLP-C, RLP-TG, TG, and RP
      than the NL group. Fasting and postprandial RLP were triglyceride enriched in the
      HTG/low HDL-C group and to a lesser extent in the CH group. The HTG/low HDL-C and
      CH groups had a delay in their RLP-C but not RLP-TG peaks suggesting a delay in
      hepatic clearance of RLP and/or a protracted period of lipolysis and/or
      processing of RLP. The fasting and postprandial RLP-C/RLP-TG and RLP-C/TG ratios
      were elevated in the apo E2/2 group in spite of gemfibrozil therapy. The
      increment in postprandial RLP was, however, not exaggerated. Our data indicate
      that 1) postprandial RLP lipemia is enhanced in HTG subjects when compared with
      NL subjects, 2) postprandial RLP lipemia is proportional to fasting RLP and TG
      levels and mirrors, to a large extent, increases in postprandial TG, RP, and VLDL
      apo B48 but not VLDL apo B100, 3) there are compositional differences in fasting
      and postprandial RLP in the three forms of HTG studied, RLP being triglyceride
      enriched in the HTG/low HDL-C group and to a lesser extent in the CH group, and
      cholesterol-enriched in the apo E2/2 group, and 4) apo E2/2 subjects had high
      fasting and postprandial RLP-C concentrations in spite of being on treatment with
      gemfibrozil and having normal fasting and postprandial TG concentrations.

PMID- 11443179
TI  - Short-term estradiol replacement in postmenopausal women selectively mutes
      somatostatin's dose-dependent inhibition of fasting growth hormone secretion.
AB  - How estradiol stimulates pulsatile GH secretion in the human is not well
      understood. Here, we test the clinical hypothesis that estradiol stimulates GH
      secretion, in part, by opposing somatostatin's inhibition of GH release. To this
      end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg
      micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively
      randomized, patient-blinded, within-subject cross-over design. For each
      intervention, the dose-dependent suppressive actions of somatostatin were
      evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h
      somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting
      state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h
      concurrently with, and for 1 h after each infusion. Serum GH concentrations were
      quantitated in an ultrasensitive chemiluminescence-based assay (detection
      threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv
      somatostatin infusions inhibited steady-state serum GH concentrations (valley
      mean during the last 60 min of the infusion interval) in a dose-dependent manner
      (P < 10(-4) interventional effect). Maximally effective doses of somatostatin
      reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific
      preinfusion baseline. Estrogen administration increased the serum estradiol
      concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L]
      (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)),
      and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean)
      serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol
      supplementation did not alter somatostatin's maximal suppression of GH by 89 +/-
      4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying
      unchanging somatostatin efficacy. In contrast, estradiol replacement
      significantly elevated the half-maximally inhibitory dose of infused somatostatin
      by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals)
      (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting
      muting of somatostatin's inhibitory potency. The latter inference was confirmed
      by a concomitant 4-fold decrease in the exponential steepness of the somatostatin
      inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs.
      0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects
      were specific, because estrogen did not alter somatostatin's dose-dependent
      enhancement (P < 10(-4)) of the orderliness of GH release patterns, as
      quantitated via the approximate entropy regularity statistic. In summary, short
      term replacement of estradiol to midfollicular phase levels in postmenopausal
      women selectively reduces the potency, but not the efficacy, of somatostatin's
      dose-dependent inhibition of GH release. Estrogen supplementation does not modify
      somatostatin's reciprocal enhancement of the quantifiable orderliness
      (approximate entropy) of the GH secretory process. Accordingly, we postulate that
      estradiol can facilitate pulsatile GH secretion, in part, by opposing the
      repressive actions of somatostatin.

PMID- 11443180
TI  - Placental regulation of insulin-like growth factor axis in monochorionic twins
      with chronic twin-twin transfusion syndrome.
AB  - To test the hypothesis that severe growth restriction (intrauterine growth
      retardation) in donor twins with chronic twin-twin transfusion syndrome (TTTS), a
      common complication of monochorionic twin pregnancy, is due to an aberration in
      the insulin-like growth factor (IGF) axis, we studied 25 sets of monochorionic
      twins with (n = 13) and without (n = 12) TTTS. Maternal and cord blood samples
      were collected at birth and analyzed for IGF-I, IGF-II, IGF-binding protein-1
      (IGFBP-1), and IGFBP-1 phosphorylation status. Fetal IGF-II levels in the
      recipient twins with TTTS were higher than those in the donor twins (829 +/- 45
      vs. 543 +/- 60 ng/mL; P < 0.001), but were comparable with those in the non-TTTS
      twin pairs. IGF-I levels in recipient and donor twin pairs were similar. The
      total IGFBP-1 concentration was higher in the donor twins than in the recipients
      (1153 +/- 296 vs. 419 +/- 108 ng/mL; P < 0.001) and non-TTTS twin pairs (P <
      0.01). The percent less phosphorylated IGFBP-1 was higher in the recipients than
      in the donor twins (P < 0.05). There were no differences in IGF-I, IGF-II, and
      IGFBP-1 levels between non-TTTS twin pairs. Maternal levels of IGFs were
      comparable in the two groups. In the TTTS group, fetal birth weight gave a
      positive correlation with serum IGF-II levels (y = 0.25x + 361.1; r = 0.47; P <
      0.05), and a negative association with IGFBP-1 levels (y = -0.72x + 1593.6; r =
      0.58; P < 0.01). Our data argue against intertwin transfusion as the cause of
      intrauterine growth retardation in the donor twin and provide evidence that the
      placenta is the key regulator of the fetal IGF axis, especially when fetal
      genotype and maternal environments are similar.

PMID- 11443181
TI  - The influence of aging and sex hormones on expression of growth hormone-releasing
      hormone in the human immune system.
AB  - GHRH is a neuropeptide that has also been localized to the immune system. The
      physiological function of GHRH in the immune system has not been elucidated. This
      study was conducted to determine whether immune GHRH expression is altered in
      certain pathological states, such as immune cell tumors, and whether gender,
      aging, and alterations in the sex steroid milieu influence the expression of this
      peptide in immune cells. Using double color flow cytometry, GHRH protein was
      found to be expressed in less than 2% of peripheral blood mononuclear cells
      (PBMC). Monocytes and B and T cells all expressed GHRH protein, although a
      greater percentage of T cells compared with B cells and monocytes expressed GHRH
      (5- to 7-fold). Semiquantitative RT-PCR was used to quantify GHRH messenger
      ribonucleic acid (mRNA) in PBMC and several immune cell-derived tumors. PBMC and
      granulocytes expressed low levels of GHRH mRNA with relatively higher levels of
      expression in monocytes. The tumor cell lines CEMX 174 (B/T cells), HUT 78 (T
      cells), WIL2-N (B cells), U937 (monocytes/macrophages), and JM 1 (pre-B cell
      lymphoma) all showed greater expression of GHRH mRNA relative to PBMC. However,
      two cell lines, CCRF-SB, a B lymphoblastoid cell line, and HL-60, a promyelocytic
      cell line, expressed GHRH mRNA at similar levels as PBMC. A significant decrease
      in the percentage of lymphocytes (CD45(+) cells) expressing GHRH protein was
      found in age-advanced men and women compared with young men and women. This
      decline was noted in B cells (CD20(+)) and monocytes (CD14(+)), but not in T
      cells (CD3(+)). GHRH mRNA expression in PBMC derived from postmenopausal women
      was lower than that from premenopausal women. However, no differences in PBMC
      GHRH mRNA expression were found in young and old men. Although in older men there
      were fewer peripheral lymphocytes that express GHRH protein, these cells secreted
      significantly more GHRH in vitro than cells from postmenopausal women with no
      hormone replacement therapy (HRT), but similar levels as cells from women
      receiving HRT. PBMC from women receiving HRT secreted more GHRH in vitro than
      cells from women receiving no hormone replacement. This study demonstrates that
      the expression of immune GHRH is dynamic, and therefore likely to be regulated.
      Increased expression of GHRH in certain immune tumors suggests that GHRH may be
      mitogenic under certain conditions and therefore play a role in the pathogenesis
      of select immune cell tumors. Collectively, these results suggest a role for GHRH
      as a local immune modulator and in the pathophysiology of immunosenescence and
      immune cell tumors.

PMID- 11443182
TI  - Osteoprotegerin serum levels in men: correlation with age, estrogen, and
      testosterone status.
AB  - Previous studies have suggested an important role for androgens and estrogens in
      bone metabolism in men. However, their local mode of action has not been clearly
      established. Osteoprotegerin (OPG) is a secreted decoy receptor that inhibits
      osteoclast formation and activity by neutralizing its cognate ligand. To assess
      the role of OPG on bone metabolism in men, we conducted a study aimed at
      evaluating OPG serum levels and their correlation with age, bone mineral density,
      biochemical markers of bone turnover, and testosterone and estradiol levels in
      252 men, aged 19-85 yr. Serum concentrations of OPG increased significantly with
      age (r = 0.41; P = 0.0001), and were positively correlated with free testosterone
      index and free estradiol index (r = 0.20; P < 0.002 and r = 0.15; P < 0.03,
      respectively) after adjustment for age and body weight. Beyond the age of 40 yr,
      OPG serum concentrations were negatively correlated with urinary excretion of
      total deoxypyridinoline (r = -0.20; P < 0.01) and PTH serum levels (r = -0.23; P
      < 0.01). In contrast, there was no correlation with biochemical markers of bone
      formation, 25-hydroxyvitamin D(3) levels, or bone mineral density at any site.
      Our data reveal that age as well as androgen and estrogen status are significant
      positive determinants, whereas PTH is a negative determinant, of OPG serum levels
      in men. These data suggest that OPG may be an important paracrine mediator of
      bone metabolism in elderly men and highlight the role of estrogens in the
      homeostasis of the male skeleton.

PMID- 11443183
TI  - Absence of an increase in the duration of the circadian melatonin secretory
      episode in totally blind human subjects.
AB  - The daily rhythm of melatonin influences multiple physiological measures,
      including sleep tendency, circadian rhythms, and reproductive function in
      seasonally breeding mammals. The biological signal for photoperiodic changes in
      seasonally breeding mammals is a change in the duration of melatonin secretion,
      which in a natural environment reflects the different durations of daylight
      across the year, with longer nights leading to a longer duration of melatonin
      secretion. These seasonal changes in the duration of melatonin secretion do not
      simply reflect the known acute suppression of melatonin secretion by ocular light
      exposure, but also represent long-term changes in the endogenous nocturnal
      melatonin episode that persist in constant conditions. As the eyes of totally
      blind individuals do not transmit ocular light information, we hypothesized that
      the duration of the melatonin secretory episode in blind subjects would be longer
      than those in sighted individuals, who are exposed to light for all their waking
      hours in an urban environment. We assessed the melatonin secretory profile during
      constant posture, dim light conditions in 17 blind and 157 sighted adults, all of
      whom were healthy and using no prescription or nonprescription medications. The
      duration of melatonin secretion was not significantly different between blind and
      sighted individuals. Healthy blind individuals after years without ocular light
      exposure do not have a longer duration of melatonin secretion than healthy
      sighted individuals.

PMID- 11443184
TI  - Missense mutations cluster within the carboxyl-terminal region of DAX-1 and
      impair transcriptional repression.
AB  - DAX-1 is an orphan nuclear receptor that plays a key role in the development and
      function of the adrenal gland and hypothalamic-pituitary gonadal axis. Mutations
      in the gene encoding DAX-1 result in X-linked adrenal hypoplasia congenita (AHC).
      Affected boys typically present with primary adrenal failure in infancy or
      childhood and hypogonadotropic hypogonadism at the time of puberty. The majority
      of DAX1 mutations described to date are nonsense or frameshift mutations that
      result in premature truncation of the DAX-1 protein and loss of DAX-1 repressor
      function. Relatively few missense mutations in DAX1 have been reported. Here, we
      describe missense mutations in three additional families with X-linked AHC. When
      combined with previous reports, the DAX1 missense mutations appear to cluster
      within restricted regions of the putative ligand-binding domain of DAX-1 and
      affect amino acids that are evolutionarily conserved, suggesting that these
      regions correspond to critical functional domains. Transcription assays, using a
      variety of artificial and native target genes, were performed to assess the
      effects of these mutations on the function of DAX-1. All DAX-1 missense mutant
      constructs showed marked loss of repressor function, with the exception of I439S,
      a mutation previously shown to be associated with delayed-onset adrenal failure
      and incomplete hypogonadotropic hypogonadism. These data indicate that most DAX1
      missense mutations associated with classic AHC exhibit marked loss of function.
      The locations of these mutations thereby identify important functional domains in
      the carboxyl-terminus of the protein.

PMID- 11443185
TI  - Mineralocorticoid receptor blockade by canrenoate increases both spontaneous and
      stimulated adrenal function in humans.
AB  - Animal studies indicate that mineralocorticoid receptors (MR) in the hippocampus
      play a major role in the glucocorticoid feedback control of the hypothalamo
      pituitary-adrenal (HPA) axis. Specifically, MR mediate the proactive feedback of
      glucocorticoids in the maintenance of basal HPA activity. The stimulatory effect
      of intracerebroventricular and intrahippocampal MR blockade on the HPA axis in
      animals has been clearly shown, whereas the effect of systemic administration of
      mineralocorticoid antagonists in humans is still contradictory. To clarify this
      point, in seven normal young women (aged 25-32 yr; body mass index, 19.0-23.0
      kg/m(2)) we studied the effects of canrenoate (CAN; 200 mg as iv bolus at 2000 h,
      followed by 200 mg infused in 500 mL saline over 4 h up to 2400 h) or placebo
      (saline, 1.0 mL as iv bolus at 2000 h, followed by 500 mL over 4 h up to 2400 h)
      on the spontaneous ACTH, cortisol, dehydroepiandrosterone (DHEA) and aldosterone
      secretion as well as on the ACTH, cortisol, and DHEA responses to human CRH (2.0
      microg/kg as iv bolus at 2200 h) or arginine vasopressin (AVP; 0.17 U/kg as im
      bolus at 2200 h). Blood samples were taken every 15 min from 2000-2400 h. During
      placebo, spontaneous ACTH and cortisol levels showed progressive decreases (P <
      0.05) from 2000-2400 h (baseline vs. nadir, mean +/- SEM, 2.0 +/- 0.3 vs. 1.4 +/-
      0.2 pmol/L and 115.1 +/- 23.7 vs. 63.5 +/- 24.3 nmol/L), whereas DHEA and
      aldosterone levels did not change. CRH induced clear increases in ACTH, cortisol,
      and DHEA levels (peaks, mean +/- SEM, 7.1 +/- 1.1 vs. 1.6 +/- 0.2 pmol/L, 322.9
      +/- 19.5 vs. 92.8 +/- 24.5 nmol/L, and 44.2 +/- 2.7 vs. 20.0 +/- 3.0 nmol/L; P <
      0.05). Similarly, AVP elicited significant increases in ACTH, cortisol, and DHEA
      levels (3.8 +/- 0.3 vs. 1.5 +/- 0.1 pmol/L, 211.9 +/- 27.2 vs. 67.7 +/- 9.7
      nmol/L, and 51.6 +/- 4.0 vs. 16.3 +/- 2.0 nmol/L; P < 0.05). During CAN
      treatment, ACTH, cortisol, and DHEA levels showed progressive rises, which begun
      at approximately 60 min and peaked between 2300 and 2400 h (ACTH, 3.4 +/- 0.4 vs.
      1.1 +/- 0.3 pmol/L; cortisol, 314.5 +/- 49.6 vs. 123.3 +/- 13.2 nmol/L; DHEA,
      52.0 +/- 8.8 vs. 21.0 +/- 2.3 nmol/L; P < 0.05 vs. baseline as well as vs. the
      same time points during placebo). Aldosterone secretion was not modified by CAN.
      The ACTH, cortisol, and DHEA responses to human CRH were enhanced by CAN (10.0 +/
      1.7 pmol/L, 462.2 +/- 36.9 nmol/L, and 66.3 +/- 8.8 nmol/L), although
      statistical significance (P < 0.05) was obtained for cortisol and DHEA only. Also
      the ACTH, cortisol and DHEA responses to AVP were amplified by CAN (8.0 +/- 2.6
      pmol/L, 324.0 +/- 34.8 nmol/L, and 77.8 +/- 4.0 nmol/L); again, statistical
      significance (P < 0.05) was obtained for cortisol and DHEA only. In conclusion,
      our study shows that the blockade of MR by CAN significantly enhances the
      activity of the HPA axis in humans, indicating a physiological role for MR in its
      control. These results also suggest that the stimulatory effect of CAN on HPA
      axis is mediated by concomitant modulation of CRH and AVP release.

PMID- 11443186
TI  - Longitudinal changes in body fat in African American and Caucasian children:
      influence of fasting insulin and insulin sensitivity.
AB  - Obesity is associated with hyperinsulinemia and reduced insulin sensitivity, both
      risk factors for type 2 diabetes. However, it is not clear whether these risk
      factors occur as a result of obesity or whether they contribute to the
      development of obesity. The aims of this study were to determine whether baseline
      (first visit) or changes in insulin measures over time were associated with
      longitudinal changes in body fat mass during growth in children. The study group
      consisted of 137 children (83 Caucasian and 54 African American) with a mean age
      of 8.1 yr at baseline. The children returned for 3-6 annual visits for
      measurement of fasting insulin, insulin sensitivity (Si), and acute insulin
      response (AIR) from the tolbutamide-modified frequent sampling iv glucose
      tolerance test and for determination of body composition by dual energy x-ray
      absorptiometry. Data were analyzed using SAS Proc mixed growth models. Total fat
      mass increased with time by 15.6%/yr (P = 0.013), but the rate of increase was
      not significantly influenced by race, sex, or Tanner stage. However, fasting
      insulin (positive effect), Si (negative effect), and AIR (positive effect) were
      significantly associated with the rate of increase in fat mass. In conclusion, in
      this cohort of children, growth-related increases in body fat were significantly
      associated with increases in fasting insulin and AIR and decreases in Si.

PMID- 11443187
TI  - Gender factors affect fatty acids-induced insulin resistance in nonobese humans:
      effects of oral steroidal contraception.
AB  - Plasma free fatty acids and intramyocellular triglycerides (IMCL) content
      modulate whole body insulin sensitivity in humans. To test whether the
      interactions between fatty acid metabolism and insulin action in nonobese humans
      are related to gender factors, we studied 15 young, normal weight, healthy men
      and 15 women matched for life habits and whole body insulin sensitivity,
      determined with the euglycemic-hyperinsulinemic clamp, by means of indirect
      calorimetry to assess substrate oxidation, localized (1)H nuclear magnetic
      resonance spectroscopy of calf muscles to assess IMCL content, and dual energy x
      ray absorption to assess body composition. In addition, to test whether
      perturbation of the feminine hormonal milieu modifies these interactions, we
      studied 15 matched females using oral steroidal contraception (OSC). Insulin
      sensitivity in women, notwithstanding increased body fatness, plasma free fatty
      acids, IMCL content, and circulating beta-hydroxybutyrate levels and reduced
      lipid oxidation, was similar to that in men. Women using OSC showed a 40%
      reduction of insulin sensitivity associated with increased plasma free fatty
      acids, beta-hydroxybutyrate, cholesterol, and triglycerides levels and a slight
      increment in IMCL content compared with women with intact hormonal cycles. In all
      groups the IMCL content was inversely related to insulin sensitivity. In
      conclusion, nonobese, healthy, young women are as insulin sensitive as men,
      notwithstanding the higher levels of postabsorptive circulating and tissue-stored
      fatty acids; OSC-induced insulin resistance is associated with abnormal fatty
      acid metabolism and loss of this gender-related feature.

PMID- 11443188
TI  - Deletion hybrid genes, due to unequal crossing over between CYP11B1 (11beta
      hydroxylase) and CYP11B2(aldosterone synthase) cause steroid 11beta-hydroxylase
      deficiency and congenital adrenal hyperplasia.
AB  - Chromosomal rearrangements are natural experiments that can provide unique
      insights into in vivo regulation of genes and physiological systems. We have
      studied a patient with congenital adrenal hyperplasia and steroid 11beta
      hydroxylase deficiency who was homozygous for a deletion of the CYP11B1 and
      CYP11B2 genes normally required for cortisol and aldosterone synthesis,
      respectively. The genes were deleted by unequal recombination between the
      tandemly arranged CYP11B genes during a previous meiosis, leaving a single hybrid
      gene consisting of the promoter and exons 1-6 of CYP11B2 and exons 7-9 of
      CYP11B1. The hybrid gene also carried an I339T mutation formed by intracodon
      recombination at the chromosomal breakpoint. The mutant complementary DNA
      corresponding to this gene was expressed in COS-1 cells and was found to have
      relatively unimpaired 11beta-hydroxylase and aldosterone synthase activities.
      Apparently the 11beta-hydroxylase deficiency and the adrenal hyperplasia are due
      to the lack of expression of this gene in the adrenal zona
      fasciculata/reticularis resulting from replacement of the CYP11B1 promoter and
      regulatory sequences by those of CYP11B2.

PMID- 11443189
TI  - Efficacy of ipriflavone in preventing adverse effects of leuprolide.
AB  - The purpose of this study was to evaluate the efficacy of ipriflavone in
      preventing bone loss, decreasing in serum cholesterol and decreasing the rate of
      appearance of vasomotor symptoms, as well as the effects of ipriflavone on
      reduction of myoma volume by estrogen deficiency during treatment with the GnRH
      analog leuprolide. One hundred two women (mean age, 44.3 +/- 0.53 yr) receiving
      leuprolide therapy for uterine leiomyoma were randomly allocated to two groups
      (group A, leuprolide only; group B, leuprolide with ipriflavone). Bone mineral
      density of the lumbar spine was measured by dual-energy x-ray absorptiometry
      before and after treatment for 6 months. Levels of serum total cholesterol (TC),
      triglyceride (TG), high-density lipoprotein cholesterol, and low-density
      lipoprotein cholesterol (LDL-C) were measured before treatment and after 3 and 6
      months of treatment. Subjects were asked to report the appearance of vasomotor
      symptoms throughout treatment. Myoma node volumes were measured before treatment
      and after treatment for 6 months. Bone mineral density was reduced in both
      groups, with reduction rates of -5.26% in group A and -3.70% in group B (P < 0.01
      vs. group A). Changes in bone markers were not significant in either group. TC
      was significantly increased in both groups, and TG levels were increased
      significantly after 3 and 6 months of treatment in group A but not in group B.
      There was no significant difference between these two groups in amount of
      increase of either TC or TG. LDL-C levels were increased significantly after 3
      and 6 months of treatment in both groups, and the differences between the groups
      (11.7% in group A vs. 7.5% in group B at 3 month and 22.6% in group A vs. 8.4% in
      group B at 6 month) were significant. Severe vasomotor symptoms were reduced in
      group B. The rates of reduction of myoma volume were 49.8% in group A and 52.9%
      in group B; this difference between groups was not significant. Ipriflavone
      efficaciously alleviated the adverse effects of estrogen deficiency such as bone
      loss and increase in LDL-C level, and the ability of leuprolide therapy to reduce
      myoma volume was not decreased by ipriflavone administration.

PMID- 11443190
TI  - Evidence that longer androgen receptor polyglutamine repeats are a causal factor
      for genital abnormalities.
AB  - Moderate to severe undermasculinized genitalia was recently shown to be
      associated with longer polyglutamine repeats within the androgen receptor
      [AR(Gln)n]. However, it was unknown whether this was because longer AR(Gln)n
      contributed to the: 1) etiology; 2) severity; and/or 3) testicular maldescent.
      Therefore, AR(Gln)n length in 175 males with abnormal genitalia were analyzed
      according to etiology (known or unknown), severity (complete, severe, and
      moderate), or testis position (abdominal, inguinal, or scrotal). Etiology (P =
      0.01) and severity (P = 0.02) but not testis position (P = 0.52) were associated
      with AR(Gln)n length. The association between the severity of the genital
      abnormalities and AR(Gln)n length was due to the close association of severity
      with the etiology (P < 0.0001). A highly selected group with moderate to severe
      genital abnormalities and multiple criteria to exclude known etiological factors
      had a greater AR(Gln)n length (mean, 25.33) than all other samples (mean, 23.11;
      P = 0.0004). The results suggest that AR(Gln)n length does not influence the
      severity of undermasculinization or testis descent but instead contributes to the
      causation of genital abnormalities in a subset of patients. These findings,
      together with a demonstrated relationship between severity and multifactorial
      etiology, are incorporated into a proposed model for the involvement of AR(Gln)n
      length in genital abnormalities.

PMID- 11443191
TI  - RET/PTC rearrangements in thyroid nodules: studies in irradiated and not
      irradiated, malignant and benign thyroid lesions in children and adults.
AB  - Rearrangements of the RET proto-oncogene may occur in both naturally occurring
      and radiation-induced papillary thyroid carcinomas. Conflicting results on the
      frequency and type of RET/PTC rearrangements have been reported in relation to
      age, radiation exposure, and histological tumor variant. We designed the present
      study to evaluate in a single laboratory, using the same methodologies, the
      pattern of RET/PTC activation in thyroid tumors from different groups of patients
      (exposed or not exposed to radiation, children or adults, with benign or
      malignant tumors) in relationship to the above mentioned variables. We studied
      154 patients with benign nodules (n = 65) or papillary thyroid cancer (n = 89).
      In the last group, 25 were Belarus children exposed to the post-Chernobyl
      radioactive fallout, 17 were Italian adults exposed to external radiotherapy for
      benign diseases, and 47 were Italian subjects (25 children and 22 adults) with no
      history of radiation exposure. Among patients with benign thyroid nodules, 21
      were Belarus subjects (18 children and 3 adults) exposed to the post-Chernobyl
      radioactive fallout, 8 were Italian adults exposed to external radiation on the
      head and neck, and 36 were Italian adults with naturally occurring benign
      nodules. The overall frequency of RET/PTC rearrangements in papillary thyroid
      cancer was 55%. The highest frequency was found in post-Chernobyl children and
      was significantly higher (P = 0.02) than that found in Italian children not
      exposed to radiation, but not significantly higher than that found in adults
      exposed to external radiation. No difference of RET/PTC rearrangements was found
      between samples from irradiated (external x-ray) or not irradiated adult
      patients, as well as between children and adults with naturally occurring, not
      irradiated, thyroid cancer. When analyzing the type of RET/PTC rearrangement
      (RET/PTC1 or RET/PTC3), no major difference was apparent. In addition, eight
      cases with an unknown RET/PTC rearrangement and three cases with the concomitant
      expression of RET/PTC1 and RET/PTC3 were found. No significant correlation was
      observed between the frequency and/or the type of RET/PTC rearrangement and
      clinical-epidemiological features of the patients such as age at diagnosis, age
      at exposure, histological variant, gender and tumor-node-metastasis (TNM)
      categories. RET/PTC rearrangements were also found in 52.4% of post-Chernobyl
      benign nodules, in 37.5% of benign nodules exposed to external radiation and in
      13.9% of naturally occurring nodules (P = 0.005, between benign post-Chernobyl
      nodules and naturally occurring nodules). The relative frequency of RET/PTC1 and
      RET/PTC3 in rearranged benign tumors showed no major difference. In conclusion,
      our results indicate that the presence of RET/PTC rearrangements in thyroid
      tumors is not restricted to the malignant phenotype, is not higher in radiation
      induced tumors compared with those naturally occurring, is not different after
      exposure to radioiodine or external radiation, and is not dependent from young
      age. Other factors, probably influenced by ethnic or genetic background, may act
      independently from or in cooperation with radiation, to trigger the DNA damage
      leading to RET proto-oncogene activation.

PMID- 11443192
TI  - Five-day pulsatile gonadotropin-releasing hormone administration unveils combined
      hypothalamic-pituitary-gonadal defects underlying profound hypoandrogenism in men
      with prolonged critical illness.
AB  - Central hyposomatotropism and hypothyroidism have been inferred in long-stay
      intensive care patients. Pronounced hypoandrogenism presumably also contributes
      to the catabolic state of critical illness. Accordingly, the present study
      appraises the mechanism(s) of failure of the gonadotropic axis in prolonged
      critically ill men by assessing the effects of pulsatile GnRH treatment in this
      unique clinical context. To this end, 15 critically ill men (mean +/- SD age, 67
      +/- 12 yr; intensive care unit stay, 25 +/- 9 days) participated, with baseline
      values compared with those of 50 age- and BMI-matched healthy men. Subjects were
      randomly allocated to 5 days of placebo or pulsatile iv GnRH administration (0.1
      microg/kg every 90 min). LH, GH, and TSH secretion was quantified by
      deconvolution analysis of serum hormone concentration-time series obtained by
      sampling every 20 min from 2100-0600 h at baseline and on nights 1 and 5 of
      treatment. Serum concentrations of gonadal and adrenal steroids, T(4), T(3),
      insulin-like growth factor I (IGF), and IGF-binding proteins as well as
      circulating levels of cytokines and selected metabolic markers were measured.
      During prolonged critical illness, pulsatile LH secretion and mean LH
      concentrations (1.8 +/- 2.2 vs. 6.0 +/- 2.2 IU/L) were low in the face of
      extremely low circulating total testosterone (0.27 +/- 0.18 vs. 12.7 +/- 4.07
      nmol/L; P < 0.0001) and relatively low estradiol (E(2); 58.3 +/- 51.9 vs. 85.7 +/
      18.6 pmol/L; P = 0.009) and sex hormone-binding globulin (39.1 +/- 11.7 vs. 48.6
      +/- 27.8 nmol/L; P = 0.01). The molar ratio of E(2)/T was elevated 37-fold in ill
      men (P < 0.0001) and correlated negatively with the mean serum LH concentrations
      (r = -0.82; P = 0.0002). Pulsatile GH and TSH secretion were suppressed (P < or =
      0.0004), as were mean serum IGF-I, IGF-binding protein-3, and acid-labile subunit
      concentrations; thyroid hormone levels; and dehydroepiandrosterone sulfate.
      Morning cortisol was within the normal range. Serum interleukin-1beta
      concentrations were normal, whereas interleukin-6 and tumor necrosis factor-alpha
      were elevated. Serum tumor necrosis factor-alpha was positively correlated with
      the molar E(2)/testosterone ratio and with type 1 procollagen; the latter was
      elevated, whereas osteocalcin was decreased. Ureagenesis and breakdown of bone
      were increased. C-Reactive protein and white blood cell counts were elevated;
      serum lactate levels were normal. Intermittent iv GnRH administration increased
      pulsatile LH secretion compared with placebo by an increment of +8.1 +/- 8.1 IU/L
      at 24 h (P = 0.001). This increase was only partially maintained after 5 days of
      treatment. GnRH pulses transiently increased serum testosterone by +174% on day 2
      (P = 0.05), whereas all other endocrine parameters remained unaltered. GnRH
      tended to increase type 1 procollagen (P = 0.06), but did not change serum
      osteocalcin levels or bone breakdown. Ureagenesis was suppressed (P < 0.0001),
      and white blood cell count (P = 0.0001), C-reactive protein (P = 0.03), and
      lactate level (P = 0.01) were increased by GnRH compared with placebo infusions.
      In conclusion, hypogonadotropic hypogonadism in prolonged critically ill men is
      only partially overcome with exogenous iv GnRH pulses, pointing to combined
      hypothalamic-pituitary-gonadal origins of the profound hypoandrogenism evident in
      this context. In view of concomitant central hyposomatotropism and
      hypothyroidism, evaluating the effectiveness of pulsatile GnRH intervention
      together with GH and TSH secretagogues will be important.

PMID- 11443193
TI  - Leptin receptor gene polymorphisms are associated with insulin in obese women
      with impaired glucose tolerance.
AB  - Leptin receptors are present on beta-cells as well as on muscle and fat cells,
      thus enabling leptin to modulate both insulin secretion and insulin action.
      Leptin inhibits especially the glucose-stimulated insulin secretion from
      pancreatic cells. The leptin receptor (LEPR) gene could thus play a role in the
      regulation of glucose and insulin after an oral glucose load. Therefore, the
      relationship between LEPR polymorphisms and glucose and insulin response to an
      oral glucose tolerance test (OGTT) was investigated. Three LEPR polymorphisms
      (Lys(109)Arg, Gln(223)Arg, and Lys(656)Asn) were typed on genomic DNA of 358
      overweight and obese women, aged 18-60 yr. Based on an OGTT, 269 subjects were
      defined with normal glucose tolerance, and 89 with impaired glucose tolerance
      (IGT). Associations between genotypes and glucose metabolism were analyzed with a
      general linear models procedure in pre- and postmenopausal women separately,
      after adjusting the data for age and fat mass. In postmenopausal women with IGT
      (n = 24), associations were found with Lys(109)Arg and Lys(656)Asn for fasting
      insulin (P = 0.05) and with Lys(109)Arg and Gln(223)Arg for the insulin response
      to an OGTT (P < 0.02). In the same group, trends were found with Lys(656)Asn for
      fasting glucose as well as in response to the OGTT. In premenopausal women with
      IGT (n = 65), associations were found with Lys(109)Arg and Lys(656)Asn for
      overall glucose response to the glucose load. In contrast, no associations with
      insulin or glucose were found in women with normal glucose tolerance. In
      conclusion, these data indicate that LEPR polymorphisms are associated with
      insulin and glucose metabolism in women with impaired glucose homeostasis.

PMID- 11443194
TI  - Mutational analysis in X-linked spondyloepiphyseal dysplasia tarda.
AB  - Spondyloepiphyseal dysplasia tarda (SEDT) is an X-linked recessive disorder
      characterized by short stature due to defective growth of the vertebral bodies.
      In addition, deformities of the femoral heads result in early onset secondary
      osteoarthritis of the hips. The disorder affects males only with heterozygous
      female carriers showing no consistent abnormalities. The gene causing SEDT, which
      is located on Xp22.12-p22.31, consists of 6 exons of which only exons 3, 4, 5,
      and 6 are translated to yield an 140 amino acid protein, referred to as SEDLIN.
      SEDLIN mutations have been observed in SEDT patients, and we have undertaken
      studies to characterize such mutations in four unrelated SEDT kindreds by DNA
      sequence analysis. We identified two nonsense and two intragenic deletional
      frameshift mutations. The nonsense mutations occurred in exons 4 (TGG-->TGA,
      Trp70Stop) and 6 (CGA-->TGA, Arg122Stop). Both of the intragenic deletions, which
      were approximately 750 bp and 1300-1445 bp in size, involved intron 5 and part of
      exon 6 and resulted in frameshifts that lead to premature termination (Stop)
      signals. Thus, all four mutations are predicted to result in truncated proteins.
      The results of our study expand the spectrum of SEDLIN mutations associated with
      SEDT, and this will help to elucidate further the role of this novel protein in
      the etiology of this form of osteochondrodysplasia.

PMID- 11443195
TI  - Antigonadotropic action of adenosine triphosphate in human granulosa-luteal
      cells: involvement of protein kinase Calpha.
AB  - The presence of P2U purinoceptor in human granulosa-luteal cells (hGLCs)
      indicates a potential role of ATP in regulating ovarian function. In this study
      an inhibitory effect of ATP on hCG-induced cAMP production was observed.
      Extracellular ATP has been shown to activate protein kinase C (PKC) after binding
      to a purinoceptor. To understand the role of PKC in mediating ATP action, hCG
      stimulated cAMP level was examined in the presence of the PKC activator, 1
      micromol/L phorbol 12-myristate 13-acetate (PMA), or the PKC inhibitor, 1
      micromol/L staurosporin or 1 micromol/L bisindolylmaleimide I. PMA, like 10
      micromol/L ATP, significantly reduced hCG-evoked cAMP production. In addition,
      the inhibitory effect of ATP was reversed by staurosporin and bisindolylmaleimide
      I. To further investigate the involvement of PKC isoforms in mediating the
      inhibitory effect of ATP, the presence of PKC isoforms in cultured hGLCs was
      examined by Western blot using monoclonal antibodies against specific isoforms.
      Translocation of PKC isoforms from cytosolic fraction to membrane fraction was
      studied to identify the active PKC isozymes subsequent to ATP treatment. The
      change in PKC isoform in PKC-depleted cells (achieved by exposure to PMA for 18
      h) was also examined. Our results demonstrated the presence of PKCalpha, -delta, 
      iota, and -lambda isoforms in hGLCs and the translocation of PKCalpha subsequent
      to ATP treatment. In PKC-depleted cells the PKCalpha level was reduced, and no
      significant effect of ATP on hCG-stimulated cAMP production was observed. To our
      knowledge, this is the first demonstration of PKC isoforms in hGLCs and the
      involvement of activated PKC in mediating the antigonadotropic effect of
      extracellular ATP. Taken together, these results further support a role of this
      neurotransmitter in regulating human ovarian function.

PMID- 11443196
TI  - Effect of glycemic optimization on electronegative low-density lipoprotein in
      diabetes: relation to nonenzymatic glycosylation and oxidative modification.
AB  - The effect of insulin therapy on low-density lipoprotein (LDL) oxidizability,
      proportion of electronegative LDL [LDL(-)] and LDL composition was studied in 33
      type 2 diabetic patients. Before glycemic control improvement, type 2 diabetic
      subjects presented higher triglyceride and very low-density lipoprotein
      cholesterol and lower high-density lipoprotein cholesterol than 25 healthy
      matched subjects. Furthermore, their LDL was more susceptible to oxidation (lag
      phase 45.9 +/- 5.4 min vs. 49.7 +/- 7.6 min, P < 0.05), contained a higher
      proportion of LDL(-) (19.0 +/- 8.7% vs. 14.3 +/- 5.5%, P < 0.05), and was
      enriched in triglyceride and depleted in cholesterol and phopholipids.
      Lipoprotein profile improved after glycemic optimization but failed to change
      either LDL oxidizability (45.3 +/- 6.2 min) or LDL(-) (17.9 +/- 8.2%). These data
      suggest that oxidation rather than nonenzymatic glycosylation could be related to
      the high LDL(-) found in these patients and disagree with results obtained in a
      previous study of type 1 diabetic patients. A second study was conducted in 10
      type 1 and 10 type 2 diabetic subjects under insulin therapy, and the proportions
      of glycated LDL (gLDL) and LDL(-) were determined. Basal gLDL (2.8 +/- 0.6%) and
      LDL(-) (20.7 +/- 6.1%) decreased in type 1 diabetics after glycemic optimization
      (1.9 +/- 0.6% and 15.4 +/- 3.4%, respectively; P < 0.05). In type 2 patients,
      even though gLDL decreased (from 2.2 +/- 0.6% to 1.6 +/- 0.6%, P < 0.05) no
      effect was observed on LDL(-) (from 17.3 +/- 2.9% to 16.0 +/- 4.3%). We conclude
      that nonenzymatic glycosylation, which appears as a determinant of the high
      proportion of LDL(-) in type 1 diabetes, does not play a major role in LDL(-)
      generation in type 2 diabetes.

PMID- 11443197
TI  - Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of
      troglitazone in obese patients with type 2 diabetes: evidence of an
      antiinflammatory action?
AB  - It has been shown recently that troglitazone exerts an anti-inflammatory effect,
      in vitro, and in experimental animals. To test these properties in humans, we
      investigated the effect of troglitazone on the proinflammatory transcription
      factor nuclear factor-kappaB and its inhibitory protein IkappaB in mononuclear
      cells (MNC) and plasma soluble intracellular adhesion molecule-1, monocyte
      chemoattractant protein-1, plasminogen activator inhibitor-1, and C-reactive
      protein. We also examined the effect of troglitazone on reactive oxygen species
      generation, p47(phox) subunit expression, 9-hydroxyoctadecadienoic acid (9-HODE),
      13-HODE, o-tyrosine, and m-tyrosine in obese patients with type 2 diabetes. Seven
      obese patients with type 2 diabetes were treated with troglitazone (400 mg/day)
      for 4 weeks. Blood samples were obtained at weekly intervals. Nuclear factor
      kappaB binding activity in MNC nuclear extracts was significantly inhibited after
      troglitazone treatment at week 1 and continued to be inhibited up to week 4. On
      the other hand, IkappaB protein levels increased significantly after troglitazone
      treatment at week 1, and this increase persisted throughout the study. Plasma
      monocyte chemoattractant protein-1 and soluble intracellular adhesion molecule-1
      concentrations did not decrease significantly after troglitazone treatment,
      although there was a trend toward inhibition. Reactive oxygen species generation
      by polymorphonuclear cells and MNC, p47(phox) subunit protein quantities,
      plasminogen activator inhibitor-1, and C-reactive protein levels decreased
      significantly after troglitazone intake. 13-HODE/linoleic acid and 9
      HODE/linoleic acid ratios also decreased after troglitazone intake. However, o
      tyrosine/phenylalanine and m-tyrosine/phenylalanine ratios did not change
      significantly. These data show that troglitazone has profound antiinflammatory
      effects in addition to antioxidant effects in obese type 2 diabetics; these
      effects may be relevant to the recently described beneficial antiatherosclerotic
      effects of troglitazone at the vascular level.

PMID- 11443198
TI  - Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in
      mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?
AB  - In view of the fact that insulin resistance is associated with atherogenesis and
      that troglitazone, an insulin sensitizer, has anti-inflammatory effects, which
      may be potentially antiatherogenic in the long term, we have now investigated
      whether insulin has potential anti-inflammatory effects. We infused 2.0 to 2.5
      IU/h in 5% dextrose (100 mL/h) iv into 10 obese subjects for 4 h followed by 5%
      dextrose alone for 2 h. The rate of insulin infusion was varied to maintain
      glucose concentrations as close to the baseline as possible. Blood samples were
      obtained before and at 2, 4, and 6 h. Subjects were also infused with 5% dextrose
      without insulin and with saline on separate occasions. Intranuclear nuclear
      factor kappaB (NFkappaB) in mononuclear cells fell at 2 and further at 4 h,
      reverting toward the baseline at 6 h (P < 0.05). IkappaB increased significantly
      at 2 h, increasing further at 4 h and remaining elevated at 6 h (P < 0.001).
      Reactive oxygen species (ROS) generation by mononuclear cells fell significantly
      at 2 h and fell further at 4 h; it partially reverted to baseline at 6 h (P <
      0.005). p47(phox) subunit, the key protein of nicotinamide adenine dinucleotide
      phosphate oxidase also fell at 2 h and 4 h, reverting toward the baseline at 6 h
      (P < 0.05). In addition, soluble intercellular adhesion molecule-1 (sICAM-1),
      monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1
      (PAI-1) fell significantly following insulin infusion. Glucose or saline
      infusions without insulin caused no alteration in NFkappaB, IkappaB, ROS
      generation, p47(phox) subunit, sICAM-1, MCP-1, or PAI-1. We conclude that insulin
      has a potent acute anti-inflammatory effect including a reduction in intranuclear
      NFkappaB, an increase in IkappaB, and decreases in ROS generation, p47(phox)
      subunit, plasma soluble intercellular adhesion molecule-1 (sICAM-1), monocyte
      chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1.
      This acute anti-inflammatory effect, if demonstrated in the long term, may have
      implications for atherosclerosis and its complications.

PMID- 11443199
TI  - Impaired regulation of glucose transporter 4 gene expression in insulin
      resistance associated with in utero undernutrition.
AB  - The aim of this study was to investigate whether insulin resistance-associated in
      utero undernutrition was related to changes in insulin action on gene expression
      of molecules involved in the insulin signaling pathway and peripheral glucose
      metabolism in muscle and adipose tissue. Thirteen insulin-resistant subjects born
      with intrauterine growth retardation (IUGR) were matched for age, gender, and
      body mass index to 13 controls. Gene expression of insulin receptor, insulin
      receptor substrate-1, p85alpha phosphatidylinositol 3-kinase, glucose transporter
      4 (GLUT4), hexokinase II, and glycogen synthase was studied in skeletal muscle at
      baseline and after a 3-h euglycemic insulin stimulation. Target messenger
      ribonucleic acid (mRNA) levels were quantified using the RT-competitive PCR
      method. Insulin-stimulated glucose uptake was significantly lower in IUGR-born
      subjects than in controls (36.9 +/- 12, 7 vs. 53.9 +/- 12.7 micromol/kg.min; P =
      0.007), affecting both the glucose oxidation rate and the nonoxidative glucose
      disposal rate. At baseline, the expression of the six genes in muscle did not
      significantly differ between the two groups. The insulin-induced changes over
      baseline were comparable in both groups for all mRNAs, except GLUT4. In contrast
      to what observed in the control group (mean increment, 49 +/- 23%; P = 0.0009),
      GLUT4 expression was not stimulated by insulin in the IUGR group (8 +/- 8%; P =
      0.42). Moreover, the magnitude of the defect in GLUT4 mRNA regulation by insulin
      was correlated to the degree of insulin resistance (r = 0.73; P = 0.01). A
      similar lack of significant GLUT4 mRNA stimulation by insulin was observed in the
      adipose tissue of IUGR-born subjects. In conclusion, insulin resistance in IUGR
      born subjects is associated with an impaired regulation of GLUT4 expression by
      insulin in muscle and adipose tissue. Our data provide additional information
      about the mechanism of insulin resistance associated with in utero undernutrition
      and strengthen the role of glucose transport in the control of insulin
      sensitivity.

PMID- 11443200
TI  - Involvement of prostaglandin E(2) in interleukin-1alpha-induced parathyroid
      hormone-related peptide production in synovial fibroblasts of patients with
      rheumatoid arthritis.
AB  - Synovial fibroblasts, established in culture from patients with RA, were treated
      with proinflammatory cytokines and prostaglandin E(2) (PGE(2)) for 24 h. These
      cells enhanced the production and the messenger RNA expression of PTH-related
      peptide (PTHrP) using proinflammatory cytokines, such as interleukin (IL)-1alpha,
      tumor necrosis factor-alpha without the coordination of other cytokines. In
      addition, PGE(2) which has been induced with IL-1, also enhanced the production
      of PTHrP. The IL-1alpha-induced PTHrP production was inhibited by PG H synthetase
      (Cox) inhibitors, indomethacin, and also by Cox-2 inhibitor, NS398. The synovial
      fibroblasts expressed PGE(2) receptor subtypes, EP2, EP3, EP4, but not EP1, as
      detected by RT-PCR. Of the PGE(2) receptor agonists, EP4 agonist showed the most
      marked induction of PTHrP, and EP2 agonist partly induced the production.
      However, these PGE(2) receptors were not induced by the treatment with IL-1alpha
      and PGE(2). These results suggest that induction of PGE(2) by IL-1alpha may be an
      important component of the PTHrP production of the inflammatory process in
      synovial tissues from patients with RA. These findings are the first to
      demonstrate that PGE(2) stimulates PTHrP production, which is mediated mostly by
      EP2 and EP4 receptors.

PMID- 11443201
TI  - Growth hormone-releasing peptide-2 stimulates GH secretion in GH-deficient
      patients with mutated GH-releasing hormone receptor.
AB  - GH-releasing peptides (GHRPs) are synthetic peptides that bind to specific
      receptors and thereby stimulate the secretion of pituitary GH. In vivo it is
      uncertain whether these peptides act directly on somatotroph cells or indirectly
      via release of GHRH from the hypothalamus. In this study we compared the
      pituitary hormone response to GHRP-2 in 11 individuals with isolated GH
      deficiency (GHD) due to a homozygous mutation of the GHRH receptor (GHRH-R) gene
      and in 8 normal unrelated controls. Basal serum GH levels were lower in the GHD
      group compared with controls [0.11 +/- 0.11 (range, <0.04 to 0.38) vs. 0.59 +/-
      0.76 microg/L (range, 0.04-2.12 microg/L); P = 0.052]. After GHRP-2
      administration there was a 4.5-fold increase in serum GH relative to baseline
      values in the GHD group (0.49 +/- 0.41 vs. 0.11 +/- 0.11 microg/L; P = 0.002),
      which was significantly less than the 79-fold increase in the control group (46.8
      +/- 17.6 vs. 0.59 +/- 0.76 microg/L; P = 0.008). Basal and post-GHRP-2 serum
      levels of ACTH, cortisol, and PRL were similar in both groups. Basal levels of
      serum TSH were significantly higher in the GHD group than in the control group
      (3.23 +/- 2.21 vs. 1.37 +/- 0.34 microIU/mL; P = 0.003). TSH levels in both
      groups did not change after GHRP-2 administration. These results suggest that an
      intact GHRH signaling system is not an absolute requirement for GHRP-2 action on
      GH secretion and that GHRP-2 has a GHRH-independent effect on pituitary
      somatotroph cells.

PMID- 11443202
TI  - Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations
      in healthy adults and leptin-deficient subjects: evidence for possible partial
      TSH regulation by leptin in humans.
AB  - Leptin signals the status of energy reserves to the brain. Leptin stimulates
      biosynthesis of TRH in vitro and influences the activity of the hypothalamic
      pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin
      and TSH display diurnal variation with a distinct nocturnal rise, we sought to
      determine whether a relationship exists between fluctuations in circulating
      leptin and TSH. We measured serum leptin and TSH levels every 7 min for 24 h in
      five healthy men and found that both leptin and TSH levels are highly organized
      and pulsatile. A similar pattern of leptin and TSH rhythms was observed, with TSH
      and leptin levels reaching a nadir in late morning and a peak in the early
      morning hours. Importantly, cosinor analysis on the absolute leptin and TSH
      levels revealed a statistically significant fit for a 24-h period and the two
      hormones showed similar probabilities of rhythm and superimposable peak values.
      Furthermore, this study shows a strong positive Pearson correlation between the
      24-h patterns of variability of leptin and TSH in healthy subjects. Finally, the
      ultradian fluctuations in leptin levels showed pattern synchrony with those of
      TSH as determined by cross-correlation analysis, by cross-approximate enthropy
      and Bayessian analysis applied independently. To further explore whether these
      associations could reflect an underlying regulation of TSH secretion by leptin,
      we also studied frequently sampled leptin and TSH levels in four brothers,
      members of a family with leptin deficiency (one normal homozygote, two
      heterozygotes, and one leptin-deficient homozygote). Leptin levels of the
      homozygous leptin-deficient subject are detectable but bioinactive, and the
      rhythm of his TSH is disorganized. 24-h pattern of leptin and TSH variability in
      the heterozygous subjects, although significantly correlated, showed a weaker
      correlation compared with the strong correlation in the normal subjects. These
      data are consistent with the possibility that leptin may regulate TSH pulsatility
      and circadian rhythmicity, but interventional studies are needed to definitively
      prove whether leptin regulates the minute-to-minute oscillations and ultradian
      rhythm of TSH levels.

PMID- 11443203
TI  - Dietary caloric restriction prevents the age-related decline in plasma melatonin
      levels of rhesus monkeys.
AB  - Rhesus monkeys exhibit an age-associated decrease in peak plasma melatonin levels
      analogous to that reported for humans. This decrease is essentially abolished in
      monkeys subjected to a 30% reduction in caloric intake over a 12-yr period. The
      caloric restriction (CR) effect does not seem to be a reversal, but rather a long
      term prevention, of the age-related decline in hormone concentrations. The age
      effect does not seem to be due to a phase shift in the peak of melatonin
      secretions, as has been observed in some populations of aged humans. It is also
      extremely unlikely that the CR effect simply reflects a phase shift, since old
      monkeys on the diet have nocturnal melatonin levels equal to or greater than
      adult fully fed controls. Thus, if peak times (approximately 0200 h) were
      actually shifted, maximal levels in old CR monkeys would be even higher. These
      findings, coupled with previous observations in humans, suggest that peak plasma
      melatonin levels may represent a possible candidate "biomarker of aging" in
      primates. Moreover, this index of age-associated physiological decrement seems to
      be inhibited by dietary CR.

PMID- 11443204
TI  - Lactate and glycerol release from adipose tissue in lean, obese, and diabetic
      women from South Africa.
AB  - Abnormalities observed in intermediary metabolism may be related to the
      pathogenesis of obesity-related diseases such as type 2 diabetes. Glycerol and
      lactate production was estimated in the sc adipose tissue of two anatomical
      regions of 10 lean (LW), 10 obese (OW), and 10 matched diabetic (DW) black urban
      women. This was done with the sc microdialysis technique and combined with
      adipose tissue blood flow (ATBF) rates calculated from (133)Xe clearance.
      Biochemical measurements were made in the postabsorptive and postprandial state.
      Bioimpedance and computed tomography scans were used to define body composition.
      DW present with more visceral fat (DW, 138 +/- 5.0; OW, 66.6 +/- 5.0 cm; P <
      0.01). This was associated with elevated free testosterone levels (DW, 1.21 +/-
      0.1; OW, 0.75 +/- 0.1 nmol/L; P < 0.05). The fasting FFA, glycerol, and lactate
      levels increased across the three groups (LW < OW < DW). During the oral glucose
      tolerance test, glucose levels were elevated in DW, with higher insulin levels [0
      h: DW, 207 +/- 8.6; OW, 100 +/- 7.2 pmol/L (P < 0.01); 1 h: DW, 410 +/- 15.2; OW,
      320 +/- 10.9 pmol/L (P < 0.05)], but with a flat Cpeptide response (1 h: DW, 932
      +/- 40; OW, 1764 +/- 40 pmol/L; P < 0.05). Plasma lactate levels increased
      significantly in LW and OW at 1 h (P < 0.001), but remained lower in LW vs. OW
      for all time points. ATBF was highest in LW [abdominal, 0 h: DW, 4.5 +/- 0.2; OW,
      1.7 mL/100 g.min (P < 0.01); femoral, 0 h: DW, 3.4 +/- 0.2; OW, 1.8 +/- 0.3
      mL/100 g.min (P < 0.01)]. ATBF did not increase in DW during the oral glucose
      tolerance test. Glycerol release (GR) was used to assess the lipolytic rate and
      was highest in LW in the abdominal area [0 h: LW, 1.7 +/- 0.2; OW, 1.1 +/- 0.2
      micromol/kg.min (P < 0.05); DW, 0.78 +/- 0.05 micromol/kg.min (P < 0.05 vs. OW)].
      By contrast, GR was higher in the femoral area of OW (0 h: OW, 1.6 +/- 0.2; LW,
      1.15 +/- 0.1 micromol/kg.min; P < 0.05). Regional differences were observed for
      GR in both OW and DW (femoral > abdominal). Lactate release (LR) was low in DW
      [abdominal, 0 h: DW, 3.5 +/- 0.4; OW, 7.8 +/- 1.0 micromol/kg.min (P < 0.001);
      femoral, 0 h: DW, 3.1 +/- 0.3; OW, 9.0 +/- 0.9 micromol/kg.min (P < 0.001)]. LR
      was appropriately low for body fat mass in LW, with a brisk increase between 0
      and 1.5 h. A negative correlation exists between GR (abdominal area) and insulin
      levels in the postabsorptive state (P < 0.0001). In conclusion, 1) the fasting
      lipolytic rate is associated with insulin levels; 2) OW and DW have more adipose
      tissue insulin resistance than LW; 3) OW and DW have a brisker lipolysis in the
      femoral area; and 4) in DW, higher visceral mass is associated with elevated free
      testosterone and FFA concentrations. Obesity in the black population is therefore
      characterized by a marked degree of adipose tissue lipolysis. This degree of
      resistance together with increasing body fat mass may predispose the obese women
      to developing type 2 diabetes. Once this disease is established, the onset of
      adipose tissue vascular insulin resistance will sustain ongoing insulin
      resistance, even in the presence of relative insulinopenia.

PMID- 11443205
TI  - Lowering total plasma insulin-like growth factor I concentrations by way of a
      novel, potent, and selective growth hormone (GH) receptor antagonist, pegvisomant
      (B2036-peg), augments the amplitude of GH secretory bursts and elevates
      basal/nonpulsatile GH release in healthy women and men.
AB  - The present clinical study implements a novel interventional strategy of short
      term profound and selective blockade of GH receptors to reduce plasma insulin
      like growth factor I (IGF-I) concentrations reversibly in healthy eumetabolic
      adults. Thereby, we examine the feedback role of systemic IGF-I on GH secretion
      without introducing the complex metabolic disarray that can otherwise accompany
      secondary IGF-I deprivation. To this end, we sampled blood at 10-min intervals
      for 10 h overnight in 8 men (aged 19-46 yr) and 4 women (aged 19-39 yr) to
      quantitate endogenous GH secretion and half-life 72 h after the prospective,
      randomly ordered, double blind, and within-subject cross-over administration of
      pegvisomant (1 mg/kg) or saline (0.5 mL) sc. Pegvisomant is an oligopegylated
      recombinant human GH peptide mutated to antagonize GH receptor-dependent
      signaling. Statistical analyses of paired plasma IGF-I concentrations and
      deconvolution-based quantitation of pulsatile GH secretion revealed that GH
      receptor blockade 1) suppressed fasting total IGF-I concentrations by 31%, viz.
      from (mean +/- SEM) 276 +/- 42 (placebo) to 190 +/- 20 microg/L (pegvisomant; P =
      0.006) 84 h after drug injection; 2) increased the 10-h mean serum GH
      concentration by 71% from 1.4 +/- 0.33 (placebo) to 2.4 +/- 0.58 (pegvisomant; P
      = 0.024); 3) augmented the amplitude of underlying GH secretory bursts by 2.1
      fold (i.e. from 0.13 +/- 0.032 to 0.27 +/- 0.076 microg/L.min; P = 0.0088); and
      4) elevated the basal/nonpulsatile rate of GH secretion by 2.5-fold (from 2.3 +/-
      0.77 to 5.07 +/- 1.8 microg/L.10 h; P = 0.022). The rise in the amplitude of GH
      secretory bursts correlated with the fall in plasma IGF-I concentrations (r =
      0.603; P = 0.038). In contrast, IGF-I depletion did not alter GH secretory pulse
      frequency, half-duration, interpulse interval, percentage of pulsatile GH
      release, or half-life of endogenous GH. In summary, selective short-term
      reduction of systemic IGF-I concentrations in healthy eumetabolic adults drives
      GH secretion via the specific bipartite neuroregulatory mechanism of amplified GH
      secretory burst amplitude and elevated basal/nonpulsatile GH release. Endogenous
      GH half-life and frequency-related features of pulsatile GH secretion are not
      measurably affected, thus identifying a highly distinctive mode of IGF-I feedback
      dependent control of GH output. As the increment in GH secretory burst amplitude
      correlated with the decrement in plasma IGF-I concentrations, we infer that
      variations in circulating IGF-I availability within the adult midphysiological
      range can influence pulsatile and basal GH production by way of negative
      feedback. Based on data in experimental animals, we speculate that the negative
      feedback actions of systemic IGF-I on GH secretion are mediated via increased
      hypothalamic somatostatin release, decreased GHRH (or GH-releasing peptide)
      secretion, and/or suppressed pituitary GH biosynthesis.

PMID- 11443206
TI  - Identification of the peptides that inhibit the function of human monoclonal
      thyroid-stimulating antibodies from phage-displayed peptide library.
AB  - Autoantibodies against TSH receptor (TSHR) are known to be involved in the
      occurrence of Graves' disease. It is obvious that mapping of epitopes of the
      autoantibodies found in the patients with Graves' disease is an important step in
      elucidating possible mechanism of generation of the autoantibodies against TSHR
      as well as in developing effective diagnostic and therapeutic approaches for
      Graves' disease. In this report we have identified the peptide sequences that
      bind to two human monoclonal thyroid-stimulating antibodies (mTSAbs; B6B7 and 101
      2) from a disulfide-constrained phage-displayed peptide library. The peptides
      selected by three rounds of biopanning showed half-maximal inhibitory activities
      for cAMP synthesis induced by mTSAbs at about 0.1 micromol/L. SPWTLGA and TQWNMQH
      selected for B6B7 and 101-2, respectively, show specificity for their respective
      antibodies. This means that different clones of mTSAbs may have different
      epitopes for TSHR. The IgG of the patient from whom B6B7 was derived binds with
      specificity to the respective immobilized peptide in an enzyme-linked
      immunosorbant assay format, and its cAMP generation was also inhibited by
      selected peptide. It may be possible that the epitopes of TSAbs identified from
      the phage-displayed peptide library could be used for the classification of
      different clones of TSAbs present in patients with Graves' disease and for
      development of drugs to treat Graves' disease.

PMID- 11443207
TI  - Hypoglycemia and resistance to ketoacidosis in a subject without functional
      insulin receptors.
AB  - Humans with congenital absence of the islets of Langerhans and mice rendered null
      for the insulin receptor rapidly develop severe hyperglycemia and ketoacidosis
      and, if untreated, die in the early neonatal period. In contrast, children with
      homozygous or compound heterozygous mutations of the insulin receptor gene,
      although hyperglycemic postprandially, survive for many months without developing
      ketoacidosis. Paradoxically, they often develop hypoglycemia. The rarity of the
      condition and the difficulties of undertaking metabolic studies in ill infants
      have limited the physiological information that might explain the clinical
      features. We studied a boy with Donohue's syndrome who represents a further
      example of the null phenotype, with two different and novel nonsense mutations in
      the alpha-subunit of the receptor. He survived for 8 months without developing
      ketoacidosis, and fasting hypoglycemia was a frequent problem. Despite the
      complete absence of insulin receptors, evidence for persistent insulin-like
      effects on fat and liver was seen; fasting plasma beta-hydroxybutyrate and
      nonesterified fatty acid levels were low, fell further during the early
      postprandial period, and failed to rise in response to hypoglycemia. The inverse
      relationships between plasma insulin and insulin-like growth factor-binding
      protein-1 levels were maintained, suggesting persistent hepatic effects of
      insulin. GH levels measured over a 6.5-h period were low throughout. Thus, the
      differences between congenital insulin deficiency vs. insulin receptor deficiency
      in humans may be explained by persistent insulinomimetic activity of the grossly
      elevated plasma insulin presumably being mediated through the type 1 insulin-like
      growth factor receptor. As GH plays a critical role in the regulation of
      ketogenesis during insulinopenia in humans, but not in rodents, this may
      contribute to the distinct phenotype of human vs. mouse insulin receptor
      knockouts.

PMID- 11443208
TI  - Clinical review 132: The sodium iodide symporter and its potential role in cancer
      therapy.

PMID- 11443209
TI  - Clinical review 133: Progress in understanding the etiology of thyroid autonomy.

PMID- 11443210
TI  - Decreased type III and V collagen expression in chorionic villi of hydatidiform
      mole.
AB  - To investigate the characteristic structure of hydatidiform mole, various types
      of collagen expression were determined in human villous tissues obtained from
      normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect
      immunofluorescent staining was performed to detect type I, III, and VI collagen
      with specific monoclonal antibodies. Collagens were also extracted from the
      villous tissues obtained from normal pregnancy and hydatidiform mole by the salt
      precipitation method. Immunohistochemical staining for type I, III, and VI
      collagen revealed weak staining of the villous stroma in hydatidiform mole
      compared with that in normal pregnancy. Both the ratios of type III to type I
      collagen and the ratios of type V to type I collagen in the villous tissues were
      significantly decreased (P < 0.05) in molar pregnancy compared with those in
      normal pregnancy. These results suggest that alterations in the distribution and
      composition of collagen might play an important role in determining the
      pathophysiology and structure of hydatidiform mole.

PMID- 11443211
TI  - Expression of reduced nicotinamide adenine dinucleotide phosphate oxidase (ThoX,
      LNOX, Duox) genes and proteins in human thyroid tissues.
AB  - The large homolog of NADPH oxidase flavoprotein LNOX2, and probably LNOX1, are
      flavoproteins involved in the thyroid H(2)O(2) generator. Western blot analysis
      of membrane proteins from normal human thyroid, using antipeptide antibodies,
      indicated that LNOX1,2 are 164-kDa glycoproteins and that N-glycosylated motifs
      account for at least 10-20 kDa of their total apparent molecular mass. Northern
      blot analysis of 23 different human tissues demonstrated that LNOX2 messenger RNA
      (mRNA) is strongly expressed only in the thyroid gland, although blast analysis
      of expressed sequence tags databases indicated that LNOX genes are also expressed
      in some nonthyroid cells. We investigated LNOX1,2 gene and protein expressions in
      normal and pathological human thyroid tissues using real-time kinetic
      quantitative PCR and antipeptide antibodies, respectively. In normal tissue,
      LNOX1,2 are localized at the apical pole of thyrocytes. Immunostaining for
      LNOX1,2 was heterogeneous, inside a given follicle, with 40-60% of positive
      follicular cells. Among normal and pathological tissues, variations of LNOX1 and
      LNOX2 mRNA levels were parallel, suggesting a similar regulation of both gene
      expressions. Whereas LNOX mRNAs seemed slightly affected in benign disease, the
      expression of protein was highly variable. In multinodular goiters, 40-60% of
      cells were stained. In hypofunctioning adenomas, LNOX immunostaining was highly
      variable among follicles, whereas sodium/iodide (Na+/I-) symporter immunostaining
      was decreased. In hyperfunctioning thyroid tissues, only few cells (0-10%) were
      weakly stained, whereas sodium/iodide symporter staining was found in the
      majority of follicular cells. In conclusion, LNOX proteins are new apical
      glycoproteins with a regulation of expression that differs from other thyroid
      markers.

PMID- 11443212
TI  - Enhanced angiogenic capacity and urokinase-type plasminogen activator expression
      by endothelial cells isolated from human endometrium.
AB  - The endometrium is a tissue unique for its cyclic destruction and rapid
      regeneration of blood vessels. Angiogenesis, indispensable for the regeneration
      process, provides a richly vascularized, receptive endometrium fundamental for
      implantation, placentation, and embryogenesis. Human endometrial microvascular
      endothelial cells (hEMVEC) were isolated to better understand the properties and
      angiogenic behavior of these cells. Unlike human foreskin microvascular
      endothelial cells (hFMVEC), which proliferated better upon stimulation by basic
      fibroblast growth factor, hEMVEC were much more sensitive to vascular endothelial
      growth factor A (VEGF-A) stimulation, probably due to enhanced VEGF receptor 2
      expression. In addition, hEMVEC displayed an enhanced expression of the urokinase
      type plasminogen activator (u-PA) compared with hFMVEC. No differences were found
      in tissue-type PA, PA inhibitor-1, and u-PA receptor expression. The high
      expression of u-PA by hEMVEC was also found in tissue sections. hEMVEC formed
      capillary-like structures when cultured in 20% human serum on top of three
      dimensional fibrin matrices, and VEGF-A or basic fibroblast growth factor
      increased this tube formation. This is in contrast with hFMVEC, which formed
      tubes only after simultaneous stimulation by a growth factor and tumor necrosis
      factor-alpha. The high basal level of u-PA contributes to and may explain the
      higher angiogenic properties of hEMVEC (in vitro).

PMID- 11443213
TI  - Reduced expression of stromal-derived factor 1 in autonomous thyroid adenomas and
      its regulation in thyroid-derived cells.
AB  - Stromal-derived factor 1 (SDF-1) and CXCR4 comprise a unique chemokine/chemokine
      receptor pair, exhibiting important functions in morphogenesis and growth
      regulation as well as attractant properties on T lymphocytes. No data are
      available on SDF-1 and CXCR4 in normal or pathological thyroid tissues. SDF-1,
      CXCR4, and CD18 messenger ribonucleic acid (mRNA) as a marker of leukocytic
      infiltration were quantified in tissues affected by thyroid adenoma (n = 11) and
      Graves' disease (GD; n = 16) using competitive RT-PCR. SDF-1 mRNA levels differed
      significantly between autonomous adenomas and the corresponding normal tissue,
      but not in GD between patients with low or high leukocyte infiltration, thyroid
      peroxidase, and TSH receptor autoantibodies, respectively. We found a strong
      correlation between CXCR4 and CD18 mRNA, which indicates CXCR4 expression by
      leukocytes. To define the cellular source of SDF-1 and CXCR4 in thyroid tissue,
      we examined various thyroid-derived cells. Fibroblasts are the most potent
      producers of SDF-1, although thyrocytes also secrete SDF-1 in vitro. Leukocytes
      showed very weak SDF-1 mRNA levels and no secretion of the chemokine.
      Immunohistology confirmed and extended these results; SDF-1 expression was found
      in fibroblasts, but not or very weakly in CD45(+) leukocytes and thyrocytes. Only
      leukocytes were CXCR4(+). As examined by flow cytometry, the number of CD3(+) T
      cells expressing CXCR4 is significantly higher in the thyroid than in peripheral
      blood. SDF-1 seems to be involved in thyroid tissue homeostasis in thyroid
      adenoma, but not in the maintenance of lymphocytic infiltration in GD.

PMID- 11443214
TI  - Luteal angiogenesis: prevention and intervention by treatment with vascular
      endothelial growth factor trap(A40).
AB  - The possibility of stimulating or inhibiting paracrine factors regulating
      angiogenesis may lead to new approaches for the treatment of pathological
      conditions of the female reproductive tract. We examined the effects of a
      clinical candidate, a soluble truncated form of the Flt-1 receptor, vascular
      endothelial growth factor trap(A40) (VEGF trap), in a primate model to determine
      its ability to prevent the onset of luteal angiogenesis or intervene with the on
      going process. Marmosets were treated from the day of ovulation until luteal day
      3 (prevention regimen) or on luteal day 3 for 1 day (intervention regimen).
      Effects of VEGF inhibition were studied by obtaining a proliferation index using
      bromodeoxyuridine incorporation, quantifying endothelial cell area using CD31,
      and assessing luteal function by plasma progesterone. After both treatments,
      intense luteal endothelial proliferation was suppressed, a concomitant decrease
      in endothelial cell area confirmed the inhibition of vascular development, and a
      marked fall in plasma progesterone levels showed that luteal function was
      compromised. In situ hybridization was used to localize and quantify compensatory
      effects on the expression of angiogenic genes. VEGF messenger ribonucleic acid
      (mRNA) expression in luteal cells was increased, whereas expression of its
      receptor, Flt, was decreased. Inhibition of VEGF resulted in localized increased
      expression of angiopoietin-2 mRNA and its receptor, Tie-2. The results show that
      the VEGF trap can prevent luteal angiogenesis and inhibit the established process
      with resultant suppression of luteal function. Luteal Flt mRNA expression is
      dependent upon VEGF, and VEGF inhibition results in abortive increases in
      expression of VEGF, angiopoietin-2, and Tie-2.

PMID- 11443215
TI  - HOXA10 expression is repressed by progesterone in the myometrium: differential
      tissue-specific regulation of HOX gene expression in the reproductive tract.
AB  - HOX genes are essential regulators of development in all multicellular organisms,
      including humans. We have previously shown that HOXA10 is expressed in the
      developing uterus and later in the adult human endometrium. HOX genes regulate
      endometrial development in response to sex steroids. Here, we demonstrate that
      HOXA10 is expressed in the myometrium as well. In situ hybridization reveals
      abundant HOXA10 expression, and Northern analysis demonstrates differential HOX
      gene expression in the myometrium throughout the menstrual cycle. HOXA10
      expression decreases in the midsecretory phase, coinciding with high serum
      progesterone levels. Treatment of primary myometrial cell cultures with
      progesterone decreases HOXA10 expression in vitro-paralleling the expression seen
      in vivo. Despite the presence of progesterone receptors in the endometrium and
      myometrium, HOXA10 is differentially regulated in each tissue by progesterone.
      HOXA10 expression is induced in the stroma and decreased in the myometrium by
      progesterone. The differential tissue-specific response of this gene in response
      to progesterone is likely mediated by sex steroid receptor coactivators or
      corepressors. Decreased myometrial expression of developmental regulatory genes
      such as HOXA10 in the nonpregnant uterus may dedifferentiate the myometrium and
      allow growth in preparation for pregnancy.

PMID- 11443216
TI  - Joint growth hormone and cortisol spontaneous secretion is more asynchronous in
      older females than in their male counterparts.
AB  - In humans, cortisol and GH are secreted in a pulsatile manner, and an interaction
      between GH and the hypothalamic-pituitary-adrenal axis has been established. In
      view of the sexually dimorphic pattern in GH secretion, we investigated the GH
      cortisol bihormonal secretory dynamics in male and female healthy older
      individuals. We studied the GH and cortisol secretory patterns in 83 healthy
      subjects (45 men and 38 women; age range, 59.4-73.0 yr) by determining serum GH
      and cortisol concentrations at 20-min intervals for 24 h. The irregularity of GH
      and cortisol secretion was assessed using approximate entropy (ApEn), a scale-
      and model-independent statistic. The synchrony of joint GH-cortisol spontaneous
      secretion was quantified using the cross-ApEn statistic. Cross-correlation
      analysis of GH and cortisol patterns was computed at various time lags covering
      the 24-h period. Mean 24-h serum GH concentrations were significantly higher in
      females (mean, 1.31 mU/L; SD, 0.87) than in males (mean, 0.88 mU/L; SD, 0.42; P =
      0.009), whereas mean 24-h serum total cortisol concentrations were higher in
      males (mean, 9.0 microg/dL; SD, 1.4) than in females (mean, 7.3 microg/dL; SD,
      1.4; P = 0.0001). GH secretion was more irregular in females (mean ApEn, 0.81;
      SD, 0.23) than in males (mean ApEn, 0.60; SD, 0.20; P < 0.001). No significant
      difference in the regularity of cortisol secretion was noted between sexes. Cross
      ApEn values of paired GH-cortisol were higher in females (mean, 1.15; SD, 0.18)
      than in males (mean, 1.01; SD, 0.16; P = 0.0003). Stepwise multiple linear
      regression analysis indicated that estradiol and insulin-like growth factor
      binding protein-3 concentrations were independently related to GH ApEn values
      (r(2) = 0.14; P = 0.01), whereas cross-ApEn values of paired GH-cortisol were
      best predicted by FSH concentrations (r(2) = 0.37; P = 0.003). Cross-correlation
      analysis revealed a significant positive correlation between GH and cortisol,
      peaking at lag time of 4.7 h in males (r = 0.30; P < 0.0001) and 4.3 h in females
      (r = 0.14; P < 0.0001), with GH leading cortisol by these time intervals. In
      addition, a significant negative correlation between the two hormones was noted
      over time, peaking at 4.7 h in males (r = -0.21; P < 0.0001) and 6.3 h in females
      (r = -0.25; P < 0.0001), with cortisol leading GH by these time intervals. The
      above results indicate that in the elderly, females have a more disordered GH
      secretory pattern and a more asynchronous joint GH-cortisol secretion than their
      male counterparts. These observations most likely reflect bidirectional
      interactions between the GH and hypothalamic-pituitary-adrenal axis in humans as
      well as diminution of subsystem integrity and synchronous control of
      interconnected hormonal systems with advancing age.

PMID- 11443217
TI  - Adenovirus-mediated targeted expression of toxic genes to adrenocorticotropin
      producing pituitary tumors using the proopiomelanocortin promoter.
AB  - Management of Cushing's disease remains challenging, despite advances in its
      diagnosis and treatment. Here, we describe a strategy for targeting the
      expression of toxic genes to ACTH-producing tumor cells using adenoviral vectors.
      The POMC promoter was used to express either a marker gene (beta-galactosidase)
      or a toxic gene [herpes simplex virus thymidine kinase (TK)]. In ACTH-producing
      AtT20 cells, infection with recombinant adenoviruses containing the POMC promoter
      (AdPOMCGal; AdPOMCTK) led to high-level gene expression. Stereotactic injection
      of AdPOMCGal into the rat pituitary resulted in localized expression of the beta
      galactosidase transgene in corticotrope cells. Cytotoxicity studies were
      performed using the TK-containing vectors and treatment with ganciclovir.
      AdPOMCTK caused greater than 95% cytotoxicity of AtT20 cells at a viral dose
      (multiplicity of infection, 5 plaque-forming units/cell) that induced minimal
      toxicity using control viruses. No cellular toxicity was seen using a
      nonpituitary cell line (T47D breast tumor cells). AtT20 cells transplanted into
      nude mice induced features of Cushing's syndrome and were used as an in vivo
      model of ACTH-producing tumors. Injection of the AdPOMCTK virus caused
      significant regression of the transplanted AtT20 tumors. These studies suggest
      that the POMC promoter may provide a useful gene therapy strategy for the
      adjunctive treatment of pituitary tumors causing ACTH-dependent Cushing's
      syndrome.

PMID- 11443218
TI  - Familial neurohypophysial diabetes insipidus in a large Dutch kindred: effect of
      the onset of diabetes on growth in children and cell biological defects of the
      mutant vasopressin prohormone.
AB  - Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant
      trait in which expression of a mutant vasopressin prohormone reduces vasopressin
      production. We investigated the NP85 Cys-->Gly mutant vasopressin prohormone in a
      large kindred in The Netherlands. We demonstrate that growth retardation is an
      important early sign in two children from this kindred, which recuperates by
      substitution therapy with 1-desamino-8-D-arginine vasopressin. To obtain clues
      about the basis for the dominant inheritance of FNDI, we analyzed the trafficking
      and processing of the mutant vasopressin prohormone in cell lines by metabolic
      labeling and immunoprecipitation. The mutant vasopressin prohormone was retained
      in the endoplasmic reticulum and thus was not processed to vasopressin. This
      defect was not caused by dimerization of the vasopressin prohormone via its
      unpaired cysteine residue. High level expression of the mutant vasopressin
      prohormone in cell lines resulted in strong accumulation in the endoplasmic
      reticulum and an altered morphology of this organelle. We hypothesize that
      disturbance of the endoplasmic reticulum results in dysfunction and ultimately
      cell death of the cells expressing the mutant prohormone. Our data support the
      hypothesis that FNDI is a progressive neurodegenerative disease with delayed
      onset of symptoms. Its treatment requires early detection of symptoms for which
      growth parameters are useful.

PMID- 11443219
TI  - Survival of human ovarian follicles from fetal to adult life: apoptosis,
      apoptosis-related proteins, and transcription factor GATA-4.
AB  - The majority of oocytes present in fetal ovaries are depleted before birth, and
      only about 400 will ovulate during the normal fertile life span. Studies on
      animals have shown that apoptosis is the mechanism behind oocyte depletion and
      follicular atresia. In the present study, we investigated the extent and
      localization of apoptosis in human fetal (aged 13-40 weeks) and adult ovaries.
      Furthermore, the expression of apoptosis-regulating proteins, bcl-2 and bax, and
      the relationship of transcription factor GATA-4 were studied. Apoptosis was found
      in ovarian follicles throughout fetal and adult life. During fetal development,
      apoptosis was localized mainly to primary oocytes and was highest between weeks
      14-28, decreasing thereafter toward term. Expression of bcl-2 was observed only
      in the youngest fetal ovaries (weeks 13-14), and bax was present in the ovaries
      throughout the entire fetal period. In adult ovaries, apoptosis was detected in
      granulosa cells of secondary and antral follicles, and Bcl-2 and bax were
      expressed from primary follicles onwards. During fetal ovarian development, GATA
      4 messenger RNA and protein were localized to the granulosa cells, with
      expression being highest in the youngest ovaries and decreasing somewhat toward
      term. The expression pattern of GATA-4 suggests that it may be involved in the
      mechanisms protecting granulosa cells from apoptosis from fetal to adult life.
      The results indicate that depletion of ovarian follicles in the human fetus
      occurs through intrinsic mechanisms of apoptosis in oocytes, and later in adult
      life the survival of growing follicles may be primarily determined by granulosa
      cell apoptosis.

PMID- 11443220
TI  - Low concentrations of the histone deacetylase inhibitor, depsipeptide (FR901228),
      increase expression of the Na(+)/I(-) symporter and iodine accumulation in poorly
      differentiated thyroid carcinoma cells.
AB  - Thyroid carcinoma accounts for the majority of deaths from endocrine cancers. A
      major cause of treatment failure is the inability to trap iodine.
      Chemotherapeutic agents with differentiating properties have been tried in an
      attempt to increase iodine uptake. We examined the ability of the novel histone
      deacetylase (HDAC) inhibitor, depsipeptide (FR901228), to modulate the expression
      of thyroid-specific genes. Four cell lines, two derived from follicular thyroid
      carcinomas (FTC 133 and FTC 236) and two derived from anaplastic thyroid
      carcinomas (SW-1736 and KAT-4) were used. In these four cell lines, a very low
      concentration of depsipeptide (1 ng/mL) increased histone acetylation and
      expression of both thyroglobulin and the Na(+)/I(-) symporter messenger RNAs.
      After 3 days, messenger RNA levels approached those of a normal thyroid control.
      Depsipeptide induced increases in (125)I accumulation indicated that a functional
      Na(+)/I(-) symporter protein was induced. Transient transfections indicate that
      the effects are mediated at least in part by a trans-activating factor. These in
      vitro results suggest that depsipeptide or other histone deacetylase inhibitors
      might be used clinically in thyroid carcinomas that are unable to trap iodine as
      an adjunct to radioiodine therapy.

PMID- 11443221
TI  - The analyses of 17beta-hydroxysteroid dehydrogenase isozymes in human endometrial
      hyperplasia and carcinoma.
AB  - Intratumoral metabolism and synthesis of estrogens are considered to play very
      important roles in the pathogenesis and development of human endometrial
      adenocarcinoma. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes
      catalyze the interconversion of estradiol (E2) and estrone and thereby serve to
      modulate the tissue levels of bioactive E2. To elucidate the possible involvement
      of this enzyme in human endometrial carcinoma, we first examined the expression
      of 17beta-HSD type 1 and type 2 in 20 normal cycling human endometria, 36
      endometrial hyperplasia, and 46 endometrial endometrioid adenocarcinoma using
      immunohistochemistry, and we then studied immunoreactivity of 17beta-HSD type 2
      using immunoblotting analyses, the activity of 17beta-HSD type 1 and type 2 using
      thin-layer chromatography and their expression using RT-PCR in endometrial
      endometrioid adenocarcinoma. We correlated these findings with various
      clinicopathological parameters to examine the biological significance of 17beta
      HSDs in human endometrial disorders. 17beta-HSD type 2 immunoreactivity in normal
      endometrium was present in all cases of secretory phase (n = 14), but not in any
      endometrial mucosa of proliferative phase (n = 6). In addition, 17beta-HSD type 2
      immunoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 17 of
      46 (37%) carcinoma cases. 17beta-HSD type 1 immunoreactivity was not detected in
      all the cases examined. In both endometrial hyperplasia and carcinoma cases there
      were significant positive correlations between 17beta-HSD type 2 and progesterone
      receptor labeling index (LI). In carcinoma cases, a significant inverse
      correlation was detected between 17beta-HSD type 2 immunoreactivity and age. In
      addition, 17beta-HSD type 2 immunoreactivity was also correlated with 17beta-HSD
      type 2 enzymatic activity, and semiquantitative analyses of 17beta-HSD type 2
      messenger RNA. No significant correlations were detected between 17beta-HSD type
      2 and estrogen receptor LI, Ki67 LI, amount of aromatase messenger RNA or
      histological grade. These data indicated that the expression of 17beta-HSD type 2
      in hyperplastic and/or neoplastic endometrium may represent altered cellular
      features through hyperplastic and neoplastic transformation. However, 17beta-HSD
      type 2 may also play some protective and/or suppressive roles toward unopposed
      estrogenic effects through inactivating E2 in situ, especially in premenopausal
      patients.

PMID- 11443222
TI  - Cellular localization of orexin receptors in human pituitary.
AB  - Orexins-A and -B are hypothalamic peptides derived from a precursor called prepro
      orexin and relationated with the stimulation of food intake. They act on G
      protein receptors named orexin receptor 1 (OX(1)R) and orexin receptor 2
      (OX(2)R), respectively. In the present study, we used RT-PCR and
      immunohistochemical techniques to detect the presence of OX(1)R and OX(2)R in
      human pituitary. A band of the expected size for both OX(1)R and OX(2)R was shown
      in human pituitary by RT-PCR. The cellular localization of OX(1)R and OX(2)R was
      carried out using histological techniques. By consecutive sections we
      demonstrated that OX(1)R was present in acidophil, diffusely distributed cells,
      which represent the half of the total adenohypophysis cell population. As was
      expected, these cells were shown to coexpress GH. OX(2)R was found in the pars
      intermedia and in clusters of basophil cells of the anterior pituitary, which
      coexpress ACTH. These results were confirmed by double immunofluorescence
      techniques. We also found focal positivity in axon terminals of neurohypophysis,
      more intense for OX(2)R than for OX(1)R. In conclusion, these results
      demonstrated for the first time that OX(1)R and OX(2)R were expressed by
      somatotrope and corticotrope cells, respectively.

PMID- 11443223
TI  - A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid
      obesity.
AB  - Mutations in the melanocortin 4 receptor gene (MC4R) are the most common cause of
      monogenic human obesity. As part of our ongoing project entitled 'Turkish Obesity
      Genome Study' we determined the nucleotide sequence of the entire coding region
      of the MC4R gene in 40 morbidly obese subjects from independent families. Here we
      report a novel heterozygous mutation (N274S) in an adult female obese individual
      (age: 52 yrs, BMI 41.7 kg/m(2), height 158 cm, weight: 104 Kg). The sister of the
      index case (age: 55 yrs, height: 160 cm, weight: 110 Kg, BMI: 43 kg/m(2)) also
      carries the same mutation. Although both sisters were morbidly obese and
      hypertensive the index case had normal plasma insulin and fasting blood glucose
      levels whereas her sister had type 2 diabetes mellitus. No abnormalities of the
      reproductive function were present. Despite marked hyperphagia in childhood both
      sisters had a history of relatively diminished intensity of appetite after the
      age of 20. Of notice, index case was diagnosed to have cyclothymia whereas her
      sister was being treated for bipolar affective disorder. Detailed clinical
      evaluation revealed normal bone mineral density and serum calcium parameters as
      well as intact thyroid axis and hypothalamus-pituitary-adrenal axis in both
      patients. The human MC4-R deficient phenotype resembles the murine deficient
      state with regard to preserved reproductive function although hyperphagia,
      increased linear growth and absence of diabetes in mice are not observed in
      humans. Affected individuals have hyperphagia in childhood, which looses
      intensity later in life, and they also present with normal height and diabetes
      mellitus. Accumulating evidence indicate that melanocortin endocrine system or
      defective melanocortin signaling has inherently different characteristics in mice
      and humans resembling the variation observed with regard to leptin deficiency in
      both species.

PMID- 11443224
TI  - Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall
      thickness in type 2 diabetes.
AB  - There have been increasing evidences that thiazolidinediones, peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonists, may have some
      antiatherogenic actions. We have previously reported that troglitazone has a
      potent inhibitory effect on common carotid arterial intima-media thickness (IMT)
      in subjects with type 2 diabetes. However, some studies suggested a possibility
      that PPARgamma activators may have protoatherogenic actions, raising concern
      about their detrimental effects in diabetic subjects. In the present study, we
      investigated the effect of treatment with pioglitazone, another PPARgamma
      agonist, on IMT in a total of 106 Japanese subjects with type 2 diabetes.
      Pioglitazone (30 mg daily) was administered for 6 months in 53 patients. Compared
      to control group (n = 53), the group given pioglitazone showed a significant
      decrease in IMT as early as 3 months after the administration. The decrease in
      IMT was also found after 6 months (IMT change: -0.084[SE 0.023] mm vs. control
      0.022[SE 0.006] mm, P < 0.001), although the difference between those after 3 and
      6 months did not reach any statistical significance. These findings indicate that
      thiazolidinediones cause an inhibition of early atherosclerotic process PPARgamma
      activation.

PMID- 11443225
TI  - Intracellular Ca2+ release sparks atrial pacemaker activity.
AB  - Electrical excitation of the mammalian heart originates from specialized
      pacemaker cells in the right atrium. Pacemaker activity depends on multiple ion
      channels and transport mechanisms that reside primarily within the plasma
      membrane. However, recent evidence indicates that intracellular Ca2+ release from
      the sarcoplasmic reticulum also contributes importantly to atrial pacemaker
      function.

PMID- 11443226
TI  - Polyamines: new cues in cellular signal transduction.
AB  - The naturally occurring polyamines putrescine, spermidine, and spermine are
      involved in signal transduction. This has been demonstrated by using inhibitors
      for polyamine biosynthesis (such as alpha-difluoromethylornithine) or adding
      polyamines to cultured cells. Different polyamines, preferentially activated
      protein kinases (tyrosine kinases and MAP kinases), stimulated the expression of
      nuclear protooncogenes (myc, jun, and fos).

PMID- 11443227
TI  - Pleiotropic functions and tissue-specific expression of erythropoietin.
AB  - Erythropoietin (EPO) is produced in the brain, uterus, and oviduct. Brain EPO
      plays a neuroprotective role, and uterine EPO is likely involved in estrogen
      dependent angiogenesis. Hypoxic induction of brain EPO markedly differs from that
      in the kidney. EPO in the uterus and oviduct is estrogen inducible.

PMID- 11443229
TI  - Molecular physiology of renal p-aminohippurate secretion.
AB  - Renal proximal tubules secrete various organic anions, including drugs and p
      aminohippurate (PAH). Uptake of PAH from blood into tubule cells occurs by
      exchange with intracellular alpha-ketoglutarate and is mediated by the organic
      anion transporter 1. PAH exit into tubule lumen is species specific and may
      involve ATP-independent and -dependent transporters.

PMID- 11443230
TI  - Molecular solutions to mammalian lens transparency.
AB  - The mammalian lens generates an internal microcirculation that maintains
      transparency in the avascular lens. Significant progress has been made in
      characterizing the membrane transport proteins associated with this circulation.
      By combining physiological and molecular evidence, a more comprehensive
      understanding of normal lens function and cataractogenesis is emerging.

PMID- 11443231
TI  - A nonconventional role of molecular chaperones: involvement in the
      cytoarchitecture.
AB  - A hallmark of chaperone action is assistance in protein folding. Indeed, folding
      of nascent prokaryotic proteins proceeds mostly as a chaperone-assisted,
      posttranslational event. On the contrary, in nonstressed eukaryotic cells folding
      related tasks of eukaryotic chaperones are restricted to a subset of proteins,
      and "jobless" chaperones may form an extension of the cytoarchitecture,
      facilitating intracellular traffic of proteins and other macromolecules.

PMID- 11443232
TI  - Molecular structure of tight junctions and their role in epithelial transport.
AB  - Tight junctions create a paracellular barrier with physiological properties that
      differ among epithelia. Among these differences are electrical resistance and
      discrimination for solute size and charge. Emerging evidence suggests that a
      large family of transmembrane proteins called the claudins create these variable
      properties.

PMID- 11443233
TI  - Small is mighty: EmrE, a multidrug transporter as an experimental paradigm.
AB  - EmrE is a multidrug transporter from Escherichia coli that functions as a
      homooligomer and is unique in its small size. In each monomer there are four
      tightly packed transmembrane segments and one membrane-embedded charged residue.
      This residue provides the basis for the coupling mechanism as part of a binding
      site "time shared" by substrates and protons.

PMID- 11443234
TI  - Energy and water balance at high altitude.
AB  - Many studies have shown that subjects lose significant amounts of body mass, fat
      mass as well as fat-free mass, during a climb to and/or a stay at high altitude.
      Altitude-induced weight loss is mainly caused by malnutrition due to hypoxia
      related satiety, independent of acute mountain sickness.

PMID- 11443235
TI  - Of slow waves and spike patches.
AB  - In the small intestines, the major task of the slow wave is to induce mechanical
      movements in the intestinal wall by generating local calcium spikes. High
      resolution electrical mapping reveals fundamental differences in propagation
      between slow waves and calcium spikes. These differences suggest that slow waves
      and spikes are propagated by different mechanisms through different cell
      networks.

PMID- 11443236
TI  - [Somatic development of asthmatic children and youth].
AB  - Systemic diseases especially the chronic ones, causing substance and oxygen
      insufficiency may lead to disturbances in growth, in the nutritional status and
      slowing of the maturation processes. Bronchial asthma is the most frequent
      inflammatory chronic disease of the respiratory system and it is estimated, that
      5-10% of the population in the development period suffers from it. Somatic
      development retardation, disturbances in the nutritional status and maturation
      may be caused by respiratory insufficiency leading to anoxia, improper
      nutritional habits, recurrent or chronic infections, long-term physical and
      mental stress, limited physical activity and also pharmacological therapy. THE
      AIM of this work was to conduct, in children with bronchial asthma, the
      evaluation of: somatic development, body proportions, nutritional status, sexual
      maturation depending on the duration and degree of severity of the disease. The
      second aim was to assess whether the assumed standard for complex treatment
      depending on the severity of the diseases may lead to normal somatic development.
      MATERIAL: In the research comprised 508 children (3 1 5 boys and 93 girls)
      between 7 and 1 5 years of age, treated for bronchial asthma in the Paediatric
      Department of the Institute of Tuberculosis and Lung Diseases in Rabka. Due to
      the multiplicity of factors influencing the course of development, the following
      were observed in the studied groups: birth weight and length, average height of
      parents (selected genetic factors); place of domicile and educational level of
      the parents (social-economic factors). The study concerned children born with
      normal birth weight and length. Evaluation of the impact of genetic factors, was
      based on the analysis of parent's height; it did not differ in the studied groups
      with regard to the women's or men's height in the average population. The
      majority of the studied children lived in towns, every third child lived in the
      country. Parents of the studied children suffering from asthma had a higher
      educational level than the Polish population. METHODS: The level of somatic
      development and body proportions were evaluated with reference to direct
      anthropometric measurements: body height and weight, head and chest
      circumference, length of trunk, width of shoulders and hips, width and depth of
      the chest, and indexes of the trunk length, shoulder-hip and chest. The
      nutritional status was evaluated by the following anthropometric measurements,
      according to WHO/FAO recommendations: circumference of the arm and thigh,
      subscapular and abdominal skinfold thickness, BMI and the arm muscle
      circumference, according to Frisancho. All the above anthropometric measurements
      and indices were analyzed in groups of children depending on the severity and
      duration of the disease (classification according to the Global Strategy for
      Asthma Management and Prevention NHLBI/WHO, NIH Publication, 1998) group I --
      episodic and mild asthma (I and II degree) duration up to 3 years, group II --
      moderate and severe asthma (III and IV degree) duration up to 3 years, group III 
      - episodic and mild asthma (I and II degree) duration over 3 years group IV --
      moderate and severe asthma (III and IV degree) duration over 3 years. The
      obtained results were compared with data for healthy Warsaw population. In order
      to compare the level and variation of different somatic measurements and indices
      in children at different ages measurement results were transformed to standard
      normal distribution with a mean of 0 and standard deviation of 1. Moreover, in
      order to evaluate the variation of features with normal distribution within the
      groups and between the studied groups, analysis of variance ANOVA was used (acc.
      to the STATISTICA programme). This enabled the comparison of anthropometric
      measurements and indices in children with bronchial asthma in the four studied
      groups. To determine the statistical significance between the arithmetical means
      of the studied features in children with bronchial asthma and in healthy
      children, the t-Student test for independent samples was applied. These
      differences between selected groups depending on the degree of severity of the
      disease and its duration and between the four groups, based on the severity of
      the disease and its duration, on one hand and healthy children on the other were
      evaluated. The features and anthropometric indexes with naturally skewed
      distribution of measurement results were evaluated using centile values and
      medians. The subscapular and abdominal skinfold thickness after calculating
      centile values, were estimated on centile charts for this feature in the Warsaw
      population. The value of the skinfold thickness in centile intervals in isolated
      groups depending on severity of the illness and its duration and in the four
      groups, considering severity and duration of illness, was also analyzed.
      (ABSTRACT TRUNCATED)

PMID- 11443237
TI  - Isomeric icosaboranes B20H26: the synchrotron structure of 1,1'-bis(nido
      decaboranyl).
AB  - An isomer of B20H26, isolated from the autolysis of nido-B10H14 in a silent
      electrical discharge, is shown to be the title compound 1,1'-bis(nido
      decaboranyl). The molecule has crystallographic inversion symmetry and a long
      intercage B-B bond of 1.704 (3) A.

PMID- 11443238
TI  - Potassium thiocyanate argentates: K3[Ag(SCN)4], K4[Ag2(SCN)6] and K[Ag(SCN)2] .
AB  - The anions of the title compounds contain [Ag(SCN)4] units, with the S atoms
      coordinating to Ag+ in a tetrahedral arrangement. Whereas in the isolated anions
      of tripotassium tetrathiocyanatoargentate(I), K3[Ag(SCN)4], (I), all SCN- groups
      are bonded as terminal ligands, in tetrapotassium di-mu-thiocyanato-S:S
      bis[dithiocyanatoargentate(I)], K4[Ag2(SCN)6], (II), two AgS4 tetrahedra share
      one common edge. In poly[potassium [argentate(I)-di-mu-thiocyanato-S:S]],
      K[Ag(SCN)2], (III), edge- and vertex-sharing of AgS4 tetrahedra results in
      infinite [Ag(SCN)2]- layers.

PMID- 11443239
TI  - Monoclinic superstructure of SrMgF4 with perovskite-type slabs.
AB  - Crystals of Ce-doped SrMgF4, strontium magnesium tetrafluoride, have been found
      to have a monoclinic P2(1) structure with doubled a and tripled c cell lengths
      compared with the orthorhombic Cmcm structure previously reported in the
      literature. The perovskite-type slabs, composed of corner-sharing MgF6 octahedra
      and Sr atoms, are stacked along the b axis. The six crystallographically
      independent MgF6 octahedra are rotated so as to provide long periodicities along
      a and c. The coordination numbers and bond distances around the six
      crystallographically independent Sr atoms are slightly different in each case. In
      the superstructure, the Sr atoms lie on local mirror planes which are thought to
      originate at the high-temperature phase transition.

PMID- 11443240
TI  - Diphenyl(2-thioxo-1,3-dithiole-4,5-dithiolato-S,S')plumbane at 295 K and
      diphenyl(2-thioxo-1,3-dithiole-4,5-dithiolato-S,S')stannane at 150 K.
AB  - Molecules of diphenyl(2-thioxo-1,3-dithiole-4,5-dithiolato-S,S')plumbane,
      [Pb(C3S5)(C6H5)2], are linked into sheets via two intermolecular Pb...S(thione)
      interactions of 3.322 (4) and 3.827 (4) A; the Pb centre has a distorted
      octahedral geometry. In contrast, molecules of diphenyl(2-thioxo-1,3-dithiole-4,5
      dithiolato-S,S')stannane, [Sn(C3S5)(C6H5)2], are linked into chains via a single
      intermolecular Sn--S(thione) interaction of 2.8174 (9) A; the Sn centre has a
      distorted trigonal-bipyramidal geometry.

PMID- 11443241
TI  - A urea complex of copper(II) hypophosphite at 293, 100 and 15 K.
AB  - The crystal structure of poly[copper(II)-di-mu-hypophosphito-mu-urea],
      [Cu(H2PO2)2(CH4N2O)]n, has been determined at 293, 100 and 15 K. The geometry of
      the hypophosphite anion is very close to ideal, with point symmetry mm2. Each Cu
      atom lies on an inversion centre and is coordinated to six O atoms from four
      hypophosphite anions and two urea molecules, forming a tetragonal bipyramid. The
      unique urea molecule lies on a twofold axis. Each hypophosphite anion in the
      structure is coordinated to two Cu atoms. The hypophosphite anions, urea
      molecules and Cu(II) cations form polymeric ribbons. The Cu(II) cations in the
      ribbon are linked together by two hypophosphite anions and a urea molecule, which
      is coordinated to Cu via an O atom. The ribbons are linked to each other by N
      H...O hydrogen bonds and form polymeric layers.

PMID- 11443242
TI  - trans-Chloro(methyl)bis(tricyclohexylphosphine)platinum(II).
AB  - The crystal structure of the title compound, [PtCl(CH3)(C18H33P)2], is
      isostructural with various platinum(II) and palladium(II) complexes containing
      two bulky tricyclohexylphosphine ligands in a trans orientation. The Pt atom
      resides on an inversion centre, resulting in a 50% statistical disorder in the
      chloro and methyl positions. The most significant geometrical parameters are Pt-P
      2.3431 (8), Pt-Cl 2.440 (4) and Pt-C1 2.179 (13) A, and P-Pt-P 180, P-Pt-Cl 89.15
      (12) and 90.85 (12), and C-Pt-Cl 172.7 (5) degrees. The effective and Tolman cone
      angles for the tricyclohexylphosphine ligands were calculated as 160 and 162
      degrees, respectively.

PMID- 11443243
TI  - Two atropisomers of tricarbonyl[eta6-6-chloro-3-(3-chloro-2-methylphenyl)-2,4,8
      trimethyl-1,2,3,4-tetrahydro-2,4-dibora-1,3-diazanaphthlene]-chromium(0).
AB  - The structures of two atropisomers of the title compound,
      [Cr(C16H18B2Cl2N2)(CO)3], are reported. For both compounds, the Cr(CO)3 moiety is
      bound to the C6 aromatic ring of the molecule; the existence of atropisomers
      resulting from the non-equivalence of both faces of the C6 aromatic ring is a
      consequence of the 3-chloro-2-methylphenyl ring being nearly perpendicular to the
      mean plane of the 2,4-dibora-1,3-diazanaphthalene ring. The orientation of the
      Cr(CO)3 tripod relative to the C6 aromatic ring is such that it is nearly
      eclipsed in one isomer (2.4 degrees rotation from being eclipsed with C--N, C--Cl
      and C--H) and slightly twisted (16.2 degrees ) from an eclipsed conformation in
      the other.

PMID- 11443244
TI  - A three-dimensional inorganic/organic hybrid material, [Ni(4,4'-bipy)3
      (H2O)2V4O12]*2.5H2O.
AB  - The title compound, poly[[[diaqua(mu-4,4'-bipyridyl)dinickel(II)]-bis(mu-4,4'
      bipyridyl)-di-mu-hexaoxodivanadate(2-)] 2.5-hydrate],
      [Ni2(V2O6)2(C10H8N2)3(H2O)2]*2.5H2O, has been prepared hydrothermally and
      characterized by elemental analyses, IR spectroscopy and single-crystal X-ray
      diffraction. The structure consists of [V2O6], [Ni(4,4'-bipy)4O2] and
      [Ni(H2O)2(4,4'-bipy)2O2] polyhedra, and water of crystallization. The Ni atoms
      and one bipyridyl group lie on centres of symmetry.

PMID- 11443245
TI  - Potassium bis(carbonato-O,O')(ethylenediamine-N,N')cobaltate(III) monohydrate at
      173 K.
AB  - The title salt, K[Co(C2H8N2)(CO3)2].H2O, consists of a distorted octahedral
      cobalt complex anion and a seven-coordinate potassium cation. Both metal atoms
      have crystallographic twofold symmetry, one C2 axis passing through the Co atom
      and C--C bond, and another along a short K--O (water) bond of 2.600 A (corrected
      for libration). The carbonate is bidentate to both cobalt and potassium and the
      water forms a hydrogen bond to a carbonate O atom.

PMID- 11443246
TI  - Dichloro(d-methionine-n,s)platinum(ii) at 130 k.
AB  - The asymmetric unit of the title compound, [PtCl2(C5H11NO2S)], a D-methionine
      derivative, contains two molecules with opposite chirality at the S atoms. The
      amino acid acts as a bidentate ligand and coordinates simultaneously through the
      N (amino) and S (thioether) atoms. The molecules are packed in pairs which are
      connected through two hydrogen bonds between the protonated carboxyl groups, with
      O.O distances of 2.633 (10) and 2.663 (12) A.

PMID- 11443247
TI  - A novel hydrogen-bonded microporous framework constructed from two different
      metal complexes.
AB  - A hydrogen-bonded coordination supramolecule, (meso-5,7,7,12,14,14-hexamethyl
      1,4,8,11-tetraazacyclotetradecane-kappa4N)nickel(II) [N,N-o-phenylenebis(oxamato)
      kappa4O,N,N',O']nickelate(II) dihydrate, [Ni(C16H36N4)][Ni(C10H4N2O6)]*2H2O or
      [Ni(meso-cth)][Ni(opba)]*2H2O, has been prepared and characterized by X-ray
      crystallographic analysis. The two complex ions, i.e. [Ni(meso-cth)]2+ and
      [Ni(opba)]2-, are hydrogen bonded to each other, resulting in two-dimensional
      neutral supramolecular sheets. The sheets stack along the a direction to produce
      a three-dimensional architecture with one-dimensional channels in which hydrogen
      bonded chains of water molecules are included.

PMID- 11443248
TI  - A pseudo-trigonal bipyramidally coordinated Pt atom in dicarbonylbis(octacarbonyl
      mu-dicyclohexylphosphidodirhenio)platinum(II).
AB  - In the title compound, [PtRe4(C12H22P)2(CO)18] or [(mu-PCy2)(CO)8Re2]2Pt(CO)2 (Cy
      is cyclohexyl), two phosphido-bridged dirhenium groups are linked by a Pt(CO)2
      unit and show different bonding patterns for stereochemical reasons. The Re--Re
      distances are 3.2620 (15) and 3.0739 (15) A, and the Pt--Re distances are 2.9165
      (12), 2.9025 (15) and 2.8548 (13) A.

PMID- 11443249
TI  - [N,N'-bis(salicylidene)-2,2-dimethyl-1,3-propanediaminate]nickel(II) and [N,N'
      bis(salicylidene)-2,2-dimethyl-1,3-propanediaminate]copper(II).
AB  - In the title compounds, [2,2'-[2,2-dimethyl-1,3
      propanediylbis(nitrilomethylidyne)]diphenolato-kappa4N,N',O,O']nickel(II),
      [Ni(C19H20N2O2)], and [2,2'-[2,2-dimethyl-1,3
      propanediylbis(nitrilomethylidyne)]diphenolato-kappa4N,N',O,O']copper(II),
      [Cu(C19H20N2O2)], the Ni(II) and Cu(II) atoms are coordinated by two iminic N and
      two phenolic O atoms of the N,N'-bis(salicylidene)-2,2-dimethyl-1,3
      propanediaminate (SALPD2-, C17H16N2O2(2-)) ligand. The geometry of the
      coordination sphere is planar in the case of the Ni(II) complex and distorted
      towards tetrahedral for the Cu(II) complex. Both complexes have a cis
      configuration imposed by the chelate ligand. The dihedral angles between the
      N/Ni/O and N/Cu/O coordination planes are 17.20 (6) and 35.13 (7) degrees,
      respectively.

PMID- 11443250
TI  - (E)-5-[hydroxyimino(phenyl)methyl]-1-methyl-3-4-dihydro-2H-pyrrolium
      trifluoromethanesulfonate.
AB  - The cation of the title compound, C12H15N2O+*CF3SO3-, exists as an E-configured
      hydroxyimino derivative conjugated with a nearly planar iminium system. The twist
      angle between the phenyl ring and the oxime group is 72.2 (2) degrees. An O-
      H...O hydrogen bond links the oxime group of the cation to the anion.

PMID- 11443251
TI  - Piperidinium 3-[(4-hydroxy-5-dimethyl-2-oxo-2H-chromen-3-yl)-phenylmethyl]-5,7
      dimethyl-2-oxo-2H-chromen-4-olate.
AB  - In the title salt, C5H12N+*C29H23O6-, both benzopyran systems are planar.
      Intermolecular N--H...O hydrogen bonds and a short O--H...O intramolecular
      hydrogen bond are observed in the structure.

PMID- 11443252
TI  - 3-(p-chlorophenyl)-4-phenyl-4,5-dihydroisoxazole-5-spiro-2'-1',2',3',4'
      tetrahydronaphthalen-1'-one.
AB  - In the title compound, C24H18ClNO2, the phenyl ring and the tetralone moiety are
      approximately orthogonal to the isoxazoline ring. The isoxazoline ring adopts an
      envelope conformation, while the cyclohexenone ring of the tetralone moiety has
      an intermediate sofa/half-chair conformation. In this structure, one C--H...N
      intermolecular and two C--H...O intramolecular hydrogen bonds occur; the H.A
      distances are 2.60, and 2.35 and 2.57 A, respectively. The molecules are held
      together by an intermolecular C--H...N hydrogen bond, forming a one-dimensional
      chain along the [100] direction.

PMID- 11443253
TI  - 10-(4-fluorophenyl)-3,3,6,6,9-pentamethyl-3,4,6,7,9,10-hexahydroacridine
      1,8(2h,5h)-dione and 10-(4-fluorophenyl)-3,3,6,6-tetramethyl-9-propyl
      3,4,6,7,9,10-hexahydroacridine-1,8(2h,5h)-dione.
AB  - 10-(4-fluorophenyl)-3,3,6,6,9-pentamethyl-3,4,6,7,9,10-hexahydroacridine
      1,8(2H,5H)-dione, C24H28FNO2, (I), crystallizes with two crystallographically
      independent molecules (which differ slightly in conformation), while 10-(4
      fluorophenyl)-9-propyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine
      1,8(2H,5H)-dione, C26H32FNO2, (II), crystallizes with one molecule per asymmetric
      unit. In both structures, the central ring in the acridine moiety is in a sofa
      conformation, while the outer rings adopt intermediate half-chair/sofa
      conformations. The central pyridine ring is orthogonal to the substituted phenyl
      ring. In both structures, the packing of the crystal is stabilized by C--H...O
      intermolecular hydrogen bonds.

PMID- 11443254
TI  - Beta-1-acetamido-4-O-beta-D-galactopyranosyl-D-glucopyranose dihydrate.
AB  - The crystal structure of the title compound, C14H25NO11*2H2O, has been
      determined. The glucose and galactose residues are in a 4C1 conformation. The N
      acetyl group has a Z-anti conformation.

PMID- 11443255
TI  - Two isostructural carboranes: 3-phenyl-1,2-dicarba-closo-dodecaborane(12) and 1
      phenyl-1,7-dicarba-closo-dodecaborane(12).
AB  - Two phenyl-substituted carboranes, 3-phenyl-1,2-dicarba-closo-dodecaborane(12),
      C8H16B10, (I), and 1-phenyl-1,7-dicarba-closo-dodecaborane(12), C8H16B10, (II),
      were found to be isostructural. Comparison of the bond angles at the ipso-C atoms
      of the phenyl substituent for (I) and (II) [117.71 (3) and 118.45 (10) degrees,
      respectively] indicates that electron donation of the carborane cage for B- and C
      substituted carboranes is different.

PMID- 11443256
TI  - 2-amino-4-(4-pyridyl)pyrimidine and the 1:1 adduct with 4-aminobenzoic acid.
AB  - The structure of the title compound, C9H8N4, comprises non-planar molecules that
      associate via pyrimidine N--H...N dimer R2(2)(8) hydrogen-bonding associations
      [N...N 3.1870 (17) A] and form linear hydrogen-bonded chains via a pyrimidine N-
      H...N(pyridyl) interaction [N...N 3.0295 (19) A]. The dihedral angle between the
      two rings is 24.57 (5) degrees. The structure of the 1:1 adduct with 4
      aminobenzoic acid, C9H8N4*C7H7NO2, exhibits a hydrogen-bonding network involving
      COOH...N(pyridyl) [O...N 2.6406 (17) A], pyrimidine N--H...N [N...N 3.0737 (19)
      and 3.1755 (18) A] and acid N--H...O interactions [N...O 3.0609 (17) and 2.981
      (2) A]. The dihedral angle between the two linked rings of the base is 38.49 (6)
      degrees and the carboxylic acid group binds to the stronger base group in
      contrast to the (less basic) complementary hydrogen-bonding site.

PMID- 11443257
TI  - p-methyltetrahomodioxacalix[4]arene.
AB  - The title compound, 7,13,21,27-tetramethyl-3,17
      dioxapentacyclo[23.3.1.1(5,9).1(11,15).1(9,23)]ditriaconta
      1(29),5,7,9(30),11(31),-12,14,19(32),20,22,25,27-dodecaene-29,30,31,32-tetraol,
      C34H36O6, assumes in the solid state a very distorted cone-like conformation
      stabilized by intramolecular simple and bifurcated hydrogen bonds involving both
      phenolic and ether O atoms. One part of the molecule, comprising an ether link,
      is included in the cavity of an adjacent calixarene related by a screw axis,
      giving rise to a one-dimensional self-inclusion polymer.

PMID- 11443258
TI  - Tris(tert-butyl)phosphine sulfide, a phosphine sulfide with three bulky
      substituents.
AB  - The title compound, C12H27PS, has crystallographic C3 symmetry. The bond angles
      at phosphorus are tetrahedral [C--P--S 109.31 (12) degrees and C--P--C 109.63
      (12) degrees ] and the P--C bond length is 1.899 (4) A. The shortest
      intermolecular contacts exist between methyl H atoms and the S atom (3.09, 3.12
      and 3.28 A). A survey of various phosphine sulfides containing three equal
      ligands (Me3PS, Et3PS, Cy3PS, tBu3PS, etc.) shows the influence of substituents
      with different steric demand on the geometry at phosphorus and on the P--C bond
      length.

PMID- 11443259
TI  - Strong hydrogen-bonded amino acid dimers in L-alanine alaninium nitrate.
AB  - The title compound, C3H7NO2*C3H8NO2+*NO3-, contains L-alanine-alaninium dimers
      bonded via the carboxyl groups by a strong asymmetric hydrogen bond with an O...O
      distance of 2.4547 (19) A. The neutral alanine molecule exists as a zwitterion,
      where the carboxyl group is dissociated and the amino group is protonated. The
      alaninium cation has both groups in their acidic form. The alanine molecule and
      the alaninium cation differ only slightly in their conformation, having an N
      C(alpha)-C=O torsion angle close to -25 degrees. The dimers and the nitrate anion
      are joined through a three-dimensional hydrogen-bond network, in which the full
      hydrogen-bonding capabilities of the amino groups of the two alanine moieties are
      realised.

PMID- 11443260
TI  - (-)-gibberic acid: hydrogen-bonding pattern of the monohydrate of a non-racemic
      tetracyclic delta-keto acid derivative of gibberellin A3.
AB  - In the the title compound, 1,7-dimethyl-8-oxo-4balpha,7alpha-gibba-1,3,4a(10a)
      triene-10beta-carboxylic acid monohydrate, C18H20O3*H2O, the water of hydration
      accepts a hydrogen bond from the carboxyl and donates hydrogen bonds to the
      carboxyl carbonyl and the ketone in two different screw-related neighbors, which
      are mutually translational, yielding a complex three-dimensional hydrogen-bonding
      array.

PMID- 11443261
TI  - The lack of C2 molecular symmetry in (1R,2R,3S,6S)-3,6-dibenzyloxycyclohex-4-ene
      1,2-diol.
AB  - The results of a single-crystal X-ray experiment and density functional theory
      calculations performed for the title compound, C20H22O4, demonstrate that the
      lowest energy conformation of this molecule does not contain C2 molecular
      symmetry.

PMID- 11443262
TI  - Amarisolide monohydrate, a 2-(beta-glucosyl)neoclerodane.
AB  - The absolute configuration of the neoclerodane glycoside amarisolide, presented
      here as the monohydrate, C26H36O9*H2O, has been determined by association with
      the known configuration of the glucose moiety. Its structure was established as
      2beta-(O-beta-D-glucopyranosyl)neocleroda-3,13(16),14-trien-15,16-epoxy-18,19
      olide. Extensive hydrogen bonding among the hydroxyl groups of the sugar moiety
      forms layers which are interconnected by water molecules.

PMID- 11443263
TI  - Ketazolam.
AB  - The title compound, 11-chloro-8,12b-dihydro-2,8-dimethyl-12b-phenyl-4H
      [1,3]oxazino[3,2-d][1,4]benzodiazepine-4,7(6H)-dione, C20H17ClN2O3, is a
      benzodiazepine with an additional d-face-fused heterocyclic ring. In the
      molecule, a dihedral angle of 86.2 (1) degrees is formed by the planes of the
      phenyl and benzo rings and the former is axially oriented from the core, i.e. the
      fused 6,7,6-tricyclic system. Both heterocycles in the core suffer significant
      deviations from planarity. The central diazepine ring is a twist-boat and the
      oxazine ring exhibits a conformation intermediate between half-chair and sofa.

PMID- 11443264
TI  - 1,6-interactions between dimethylamino and aldehyde groups in two biphenyl
      derivatives.
AB  - The title compounds, 2-(dimethylamino)biphenyl-2'-carboxaldehyde, C15H15NO, and 2
      (dimethylamino)biphenyl-2',6'-dicarboxaldehyde, C16H15NO2, show similar 1,6
      interactions [N...C=O 2.929 (3) to 3.029 (3) A] between the dimethylamino and
      aldehyde groups located in the ortho positions of the two rings, which lie at
      58.1 (1)-62.4 (1) degrees to each other.

PMID- 11443265
TI  - Chlorotris(N,N'-dicyclohexylthiourea-S)tellurium(II) chloride, a tellurium
      complex with a TeClS3 coordination sphere.
AB  - During the synthesis of a series of square-planar [TeCl2(stu)2] complexes, where
      stu represents bulky di- or tetrasubstituted thioureas, the title compound,
      [TeCl[(C6H11NH)2CS]3]Cl or C39H72ClN6S3Te+*Cl-, was the unexpected result when
      stu was N,N'-dicyclohexylthiourea. The complex is square planar, with Te-S
      distances of 2.5803 (4), 2.6211 (4) and 2.8214 (4) A, and a Te-Cl distance of
      2.6485 (4) A, indicating a small trans influence of the thiourea ligand.

PMID- 11443266
TI  - trans-4-[(4-dimethylaminophenyl)-iminomethyl]-N-methyllpyridinium para
      toluenesulfonate.
AB  - In the title compound, C15H18N3+*C7H7O3S-, the phenylene and pyridyl rings are
      somewhat twisted with respect to each other, forming a dihedral angle of 23.49
      (6) degrees. The compound contains a dipolar chromophoric cation, but
      crystallizes in the centrosymmetric space group P2(1)/n and is thus not expected
      to display quadratic non-linear optical effects.

PMID- 11443267
TI  - 5-(2-pyridyl)-1,3-dithiane-2-thione.
AB  - The title compound, C9H9NS3, crystallizes with two molecules in the asymmetric
      unit. In both molecules, the dithiane-2-thione rings adopt a symmetric half-boat
      conformation with the C atom opposite the C--S(thione) bond out of the plane. The
      pyridine ring is in an equatorial position and is twisted out of the plane of the
      half-boat by 82.7 (2) and 84.5 (2) degrees in the two molecules, so that the N
      atom is trans to the axial C--H bond in both cases.

PMID- 11443268
TI  - A series of three (E)-2-alkylidene-1,4-di-p-tosyl-1,2,3,4-tetrahydroquinoxaline
      compounds.
AB  - The three title quinoxaline derivatives, (E)-2-(4-methylbenzylidene)-1,4-di-p
      tosyl-1,2,3,4-tetrahydroquinoxaline, C30H28N2O4S2, (II), (E)-2-(4
      methoxybenzylidene)-1,4-di-p-tosyl-1,2,3,4-tetrahydroquinoxaline, C30H28N2O5S2,
      (III), and (E)-2-(3-chlorobenzylidene)-1,4-di-p-tosyl-1,2,3,4
      tetrahydroquinoxaline, C29H25ClN2O4S2, (IV), were synthesized by palladium
      catalyzed hetero-annulation. The E configuration of the exocyclic double bond in
      the three compounds has been established by the present X-ray study. The
      saturated part of the quinoxaline moiety in all three compounds assumes a
      distorted chair conformation. The numerical descriptors indicate a high degree of
      isostructurality between compounds (II) and (III), but no isostructurality with
      compound (IV).

PMID- 11443269
TI  - Intermolecular contacts in the crystal packing of 2,2'-(N,N'-oxalyldiimino)bis(3
      phenylpropanamide) dimethyl sulfoxide solvate.
AB  - In the title compound, C20H22N4O4*C2H6OS, two distinct hydrogen-bond systems
      connect oxalamide groups in one pattern and primary amide groups in the other to
      form a two-dimensional network perpendicular to the c axis. These hydrophilic
      layers are joined to the three-dimensional structure through C--H...pi
      interactions. The hydrogen-bonded waved layers shape holes which are occupied by
      disordered dimethyl sulfoxide solvent molecules.

PMID- 11443270
TI  - 2,9-bis(3-nitrophenyl)-1-azaadamantan-4-one.
AB  - The title compound, 2,9-bis(3-nitrophenyl)-1-azatricyclo[3.3.1.1(3,7)]decan-4
      one, C21H19N3O5, has a tricyclic structure. The torsion angles may be used to
      describe the relationship of the carbonyl group to the adjacent faces, whereby it
      is seen that the angles on the face of the arylpiperidinone side [122.0 (3) and 
      122.0 (3) degrees ] are greater than those on the cyclohexanone side [-119.8 (4)
      and 119.9 (4) degrees ]. Although these differences may explain a facial
      selectivity during nucleophilic addition to the carbonyl group, the presence of
      the aryl rings is probably also important.

PMID- 11443271
TI  - Octafluoronaphthalene-diphenylacetylene (1/1).
AB  - The structure of the title complex, C10F8*C14H10, comprises mixed stacks of
      alternating diphenylacetylene and octafluoronaphthalene molecules, both lying at
      inversion centres and parallel to within 8.6 (1) degrees, in contrast with the
      herring-bone packing observed in crystals of either pure component.

PMID- 11443272
TI  - Melaminium bis(4-hydroxybenzenesulfonate) dihydrate.
AB  - The crystals of a new melaminium salt, 2,4,6-triamino-1,3,5-triazine-1,3-diium
      bis(4-hydroxybenzenesulfonate) dihydrate, C3H8N6(2+)*2C6H5O4S-*2H2O, are built up
      from doubly protonated melaminium(2+) residues, dissociated p-phenolsulfonate
      anions and water molecules. The doubly protonated melaminium dication lies on a
      twofold axis. The hydroxyl group of the p-hydroxybenzenesulfonate residue is
      roughly coplanar with the phenyl ring [dihedral angle 13 (2) degrees ]. A
      combination of ionic and donor-acceptor hydrogen-bond interactions link the
      melaminium and p-hydroxybenzenesulfonate residues and the water molecules to form
      a three-dimensional network.

PMID- 11443273
TI  - 2:1 complexes of 2-chloro-4-nitrobenzoic acid and 2-chloro-5-nitrobenzoic acid
      with pyrazine.
AB  - 2-chloro-4-nitrobenzoic acid and 2-chloro-5-nitrobenzoic acid form O--H...N
      hydrogen bonds with pyrazine to afford 2:1 complexes of 2C7H4ClNO4*C4H4N2, (I)
      and (II), respectively, that are located on inversion centers. The
      2C7H4ClNO4*C4H4N2 units in both complexes are connected by weak C--H...O hydrogen
      bonds; the units build a three-dimensional hydrogen-bond network in (I) and a
      ribbon structure in (II).

PMID- 11443274
TI  - A simple compound with an unexpectedly complex structure: 4-pyridone 6/5-hydrate.
AB  - The crystal structure of the title compound, C5H5NO*6/5H2O, contains five
      independent molecules of pyridone and six independent water molecules. The space
      group is P2(1), but four of the pyridones and four waters correspond closely to
      P2(1)/n. The packing involves two layers; one consists of head-to-tail chains of
      pyridone molecules 1-4 linked by N--H...O hydrogen bonds, and a second layer
      involves all the waters and the fifth pyridone. The layers are linked by hydrogen
      bonds from water to pyridone oxygen. The four water O atoms that accept only one
      classical hydrogen bond have their environment completed by C--H...O
      interactions.

PMID- 11443275
TI  - Filamentous fungus Aspergillus oryzae has two types of alpha-1,2-mannosidases,
      one of which is a microsomal enzyme that removes a single mannose residue from
      Man9GlcNAc2.
AB  - alpha-Mannosidase activities towards high-mannose oligosaccharides were examined
      with a detergent-solubilized microsomal preparation from a filamentous fungus,
      Aspergillus oryzae. In the enzymatic reaction, the pyridylaminated substrate
      Man(9)GlcNAc(2)-PA was trimmed to Man(8)GlcNAc(2)-PA which lacked one alpha-1,2
      mannose residue at the nonreducing terminus of the middle branch (Man8B isomer),
      and this mannooligosaccharide remained predominant through the overall reaction.
      Trimming was optimal at pH 7.0 in PIPES buffer in the presence of calcium ion and
      kifunensine was inhibitory with IC(50) below 0.1 microM. These results suggest
      that the activity is the same type as was previously observed with human and
      yeast endoplasmic reticulum (ER) alpha-mannosidases. Considering these results
      together with previous data on a fungal alpha-1,2-mannosidase that trimmed
      Man(9)GlcNAc(2) to Man(5)GlcNAc(2) (Ichishima, E., et al. (1999) Biochem J, 339:
      589-597), the filamentous fungi appear to have two types of alpha-1,2
      mannosidases, each of which acts differently on N-linked mannooligosaccharides.

PMID- 11443276
TI  - Structural studies of the glycopeptides of B-chain of cinnamomin--a type II
      ribosome-inactivating protein by nuclear magnetic resonance.
AB  - Cinnamomin is a plant type II ribosome-inactivating protein (RIP) isolated from
      the seeds of Cinnamomum camphora. It consists of two nonidentical polypeptide
      chains (A- and B-chain) held together through one disulfide linkage. Its A- and B
      chain contain 0.3% and 3.9% sugars respectively. The B-chain of cinnamomin was
      digested by pronase E and then the liberated glycopeptides were separated from
      non-glycopeptides by gel filtration chromatography on a Bio-Gel P-4 column. Three
      crude glycopeptides were obtained by continuing chromatography over anion
      exchange resin (AG1-X2) in the buffer of 2% pyridine-acetic acid (pH 8.3) with a
      polygradient elution system. Through further purification by the gel filtration
      chromatography and HPLC, three major glycopeptides, GP1, GP2 and GP3 were
      obtained. Mainly by two-dimensional Nuclear Magnetic Resonance (NMR) including
      TOCSY, DQF-COSY, NOESY, HMQC and HMBC, their primary structures were analyzed as:
      Man?balpha1,3Man?balpha1,6(Man?balpha1,3)(Xyl?bbeta1,2)Man?bbeta1,4GlcNAc?bbeta1,
      GlcNAc?bbeta1-(Gly-)Asn-Asn-Thr(GP1),
      Man?balpha1,6(Man?balpha1,3)(Xyl?bbeta1,2)Man?bbeta1,4GlcNAc?bbeta1,4(Fuc?balpha1
      3)GlcNAc?bbeta1-Asn-Ala
      Thr(GP2),Man?balpha1,6(Man?balpha1,3)Man?balpha1,6(Man?balpha 1,2
      Man?balpha1,3)Man?bbeta1,4GlcNAc?bbeta1,4GlcNAc?bbeta1-(Ala-)Asn-Gly-Thr(GP3).

PMID- 11443277
TI  - Reverse hyaluronan substrate gel zymography procedure for the detection of
      hyaluronidase inhibitors.
AB  - Little is known of the ubiquitous inhibitors of hyaluronidase, molecules that may
      be important for the deposition of hyaluronan. A reverse hyaluronan-substrate gel
      procedure is described here that detects such inhibitors, even in crude
      biological extracts, and is independent of the catalytic mechanism of the target
      enzyme. Following electrophoresis, hyaluronan-containing gels are incubated in a
      hyaluronidase solution. Alcian blue-staining bands indicate hyaluronan protected
      from degradation and the location of hyaluronidase inhibitors. Coordinated use of
      hyaluronan substrate gel and reverse substrate gel procedures provides estimates
      of the number and relative molecular sizes of both enzymes and their inhibitors.

PMID- 11443278
TI  - The oligosaccharyltransferase complex from pig liver: cDNA cloning, expression
      and functional characterisation.
AB  - Oligosaccharyltransferase (OST) is an oligomeric protein complex which catalyses
      the transfer en bloc of Glc(3)-Man(9)-GlcNAc(2) from Dol-PP to specific
      asparagine residues in the nascent polypeptide chain. In order to study the
      function of the pig enzyme subunits, we have cloned OST48, ribophorin I and
      ribophorin II and characterized these proteins after in vitro translation as well
      as after expression in COS-1 cells. The individual full-length cDNAs contained
      open reading frames (ORFs) encoding polypeptides with calculated molecular masses
      of approximately 48.9 kDa (OST48), approximately 68.7 kDa (ribophorin I) and
      approximately 69.3kDa (ribophorin II), respectively. A Kyte and Doolittle
      hydrophobicity analysis revealed that OST48, ribophorin I and ribophorin II
      possess a type I membrane topology with the bulk of their polypeptide chains
      directed towards the ER-lumen. In contrast to OST48, ribophorin I and II contain,
      respectively, three or two potential N-glycosylation sites of the Asn-Xaa-Thr/Ser
      type; only one is found to function as the acceptor site in each protein.
      Transfection of COS-1 cells with vector constructs encoding either OST48,
      ribophorin I, or a ribophorin I variant tagged with a myc-peptide sequence,
      resulted in the over-expression of polypeptides whose molecular masses were
      similar to those calculated from the respective cDNA ORFs. None of these three
      polypeptides, or ribophorin II, were found to display OST activity when over
      expressed alone. By contrast, a modest but reproducible approximately 25%
      increase of activity was observed when OST48 together with ribophorin I, or OST48
      and myc-tagged ribophorin I, were co-expressed, indicating that these two
      subunits are probably responsible for the catalytic activity in the hetero
      oligomeric OST complex. The only modest over-expression of transferase activity
      suggests that either the dimeric enzyme complex is catalytically unstable, or
      that the OST48 and ribophorin I polypeptides are unable to fold properly when
      other subunit components of the hetero-oligomeric OST complex are lacking. OST48
      as well as ribophorin I are expressed in COS-1 cells as ER-resident proteins.
      Whereas OST48 carries a double-lysine motif in the -3/-5 position of its
      cytosolic C-terminal domain, ribophorin I does not contain recognizable ER
      retention information. Replacing the lysine residue in the -3 position by leucine
      resulted in plasma membrane expression of the OST48-Leu polypeptide, indicating
      that this sequence motif may be able to influence OST48 localisation. No cell
      surface staining was observed when OST48-Leu was co-expressed with ribophorin I.
      This suggests that localisation of OST48 in the ER is mediated by interaction
      with ribophorin I rather than by the double-lysine motif.

PMID- 11443279
TI  - Retinoic acid induction of sialyltransferase activity in neuroblastoma cells of
      differing sialylation potentials.
AB  - In order to determine how glycosylation changes associated with cellular
      differentiation may be influenced by the basal cellular sialylation potential,
      the effect of retinoic acid (RA)-induced differentiation was investigated in
      neuroblastoma cells expressing differing levels (and activities) of the
      alpha2,6(N) sialyltransferase (ST6N) enzyme. The increase in ST activity was
      proportional to the basal cellular sialylation potentials with the high activity
      clones showing the greatest increase. This was paralleled by an up-regulation of
      the level of overall sialoglycoprotein glycosylation level. An increase in the
      levels of the polysialic acid (PSA) epitope was associated with a parallel
      increase in the levels of the neural cell adhesion molecule (NCAM) protein
      backbone although there was no overall change in the PSA:NCAM ratio following RA
      treatment.

PMID- 11443280
TI  - Inhibitory activity of sulphoglycolipid derivatives towards pancreatic trypsin.
AB  - Amphipathic sulpholipids have been shown to inhibit pancreatic serine proteases
      due to their detergent-like properties. To evaluate the structural requirement
      for this inhibitory activity, we examined the effects of various derivatives of
      sulphoglycolipids, some of which were prepared by deacylation with sphingolipid
      ceramide N-deacylase, followed by acylation with acyl chloride, on the activity
      of pancreatic trypsin. Both deacylated sulphatides and seminolipids exhibited
      inhibitory activity towards trypsin without any requirement for solubilisation
      and preincubation. On the other hand, stronger inhibition was observed for
      acylated sulphatides than for deacylated ones, but increasing the chain length of
      the fatty acid moiety resulted in the need for a solubilisation agent and
      preincubation in order to achieve maximal inhibitory activity. The structural
      isomers of sulphoglycolipids, such as I(6)SO(3)-GalCer, and phytosphingosine- and
      diglyceride-containing sulphoglycolipids, showed similar inhibitory activity,
      indicating the involvement of sulphate and hydrophobic groups, irrespective of
      the fine structure, in the inhibition. Among the sulphoglycolipids examined,
      II(3)SO(3)-LacCer was found to exhibit the highest inhibitory activity.

PMID- 11443281
TI  - Biosynthesis of glycosaminoglycans and proteoglycans by the lymph node.
AB  - Previous studies of hyaluronan uptake and catabolism by lymph nodes indicated
      that the nodes might also add some HA of low molecular weight to the unabsorbed
      fraction that passes through from afferent to efferent lymph vessels. The ability
      of lymph nodes to synthesise HA and proteoglycans was therefore examined (i) by
      perfusion of [(3)H] acetate through an afferent lymph vessel in vivo, and
      recovery of labeled products from the efferent lymph vessel and from the node
      after perfusion; and (ii) by tissue culture of lymph nodes with [(3)H] acetate.
      Perfusion of lymph nodes with [(3)H] acetate in situ yielded: (a), in outflowing
      lymph, small amounts of chondroitin/dermatan sulfate within the first hour which
      continued to be produced for up to 24 h; heparin in the second hour and HA in the
      third. In the nodes removed 17 to 19 h later, equal amounts of hyaluronan and
      chondroitin/dermatan sulfate and heparan sulfate proteoglycans were detected. In
      the tissue culture of lymph nodes: (1) HA, heparin and proteoglycans of heparan
      sulfate and chondroitin/dermatan sulfate were released into the medium but in the
      cell extract only heparan sulfate proteoglycan was detected; and (ii) molecular
      weight of the released hyaluronan ranged widely but was mostly less than 4
      5x10(5)D; heparan sulfate proteoglycan was 2.8x10(4) to 9.4x10(5)D; heparin
      7.9x10(4)D and chondroitin sulfate 1.3x10(4)D, suggesting that the chondrotin
      sulfate were released from their proteoglycans core by enzymic degradation. It is
      concluded that lymph nodes can release HA, heparin, heparan sulfate and
      chondroitin/dermatan sulfate proteoglycans into efferent lymph but the amount of
      hyaluronan is likely to be small without immune or other stimulation and its
      molecular weight is lower than in other tissues.

PMID- 11443282
TI  - A novel CFTR disease-associated mutation causes addition of an extra N-linked
      oligosaccharide.
AB  - We have examined the influence of a novel missense mutation in the fourth
      extracytoplasmic loop (EL4) of CFTR detected in a patient with cystic fibrosis.
      This substitution (T908N) creates a consensus sequence (N X S/T) for addition of
      an N-linked oligosaccharide chain near the C-terminal end of EL4. Oligosaccharyl
      transferase generally does not have access to this consensus sequence if it is
      closer than about twelve amino acids from the membrane. However, the T908N site
      is used, even though it is within four residues of the predicted membrane
      interface and the oligosaccharide chain added binds calnexin, a resident
      chaperone of the ER membrane. The chloride channel activity of this variant CFTR
      is abnormal as evidenced by a reduced rate of (36)Cl(-) efflux and a noisy single
      channel open state. This may reflect some displacement of the membrane spanning
      sequence C-terminal of EL4 since it contains residues influencing the ion pore.

PMID- 11443283
TI  - The carbohydrate deposits detected by histochemical methods in the molecular
      layer of the dentate gyrus in the hippocampal formation of patients with
      schizophrenia, Down's syndrome and dementia, and aged person.
AB  - Post-mortem brain tissue was obtained from 28 patients with brain disorders, of
      which 15 had clinically diagnosed schizophrenia, 6 Alzheimer type dementia, 5
      dementia with tangles and 2 cases of Down's syndrome. The controls were 22 cases
      from autopsies without brain disorders or with no known episodes of brain
      disorder. The tissues were stained for the detection of carbohydrate deposits in
      the hippocampal formation, using lectin, immunohistochemical and conventional
      staining methods. The staining revealed the existence of spherical deposits in
      the inner and middle molecular layers of the dentate gyrus in the hippocampal
      formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl
      glucosamine, sialic acid, mannose and chondroitin sulfate. The number of the
      deposits was higher in patients with brain disorder such as schizophrenia,
      Alzheimer type dementia, dementia with tangles or Down's syndrome, and in some
      aged individuals, in comparison to those in younger individuals. No deposits were
      detected in a few younger or aged individuals. Spherical deposits 3-10 microm in
      diameter may be an immature form of the corpora amylacea, since they were similar
      in the histochemical characteristics with lectin, immunohistochemical and
      conventional staining methods. However, differing staining ability by
      hematoxylin, periodic acid Schiff's reagent and antibodies against the
      intracellular degraded proteins such as ubiquitin and tau-protein was observed.
      The antibodies against ubiquitin and tau-protein showed clear reactivity with the
      corpora amylacea and no reactivity with spherical deposits, indicating that the
      corpora amylacea has an intracellular origin and spherical deposits an
      extracellular matrix origin. The results obtained in this study indicate that not
      only neuronal degeneration but also unusual glycometabolism in neurons may
      disturb the neuronal function and cause brain disorders, and that spherical
      deposits may cause dysfunction of the neuronal network in the dentate gyrus of
      the hippocampus which is closely linked with recognition and memory functions.

PMID- 11443284
TI  - A neurodynamical model of visual attention: feedback enhancement of spatial
      resolution in a hierarchical system.
AB  - Human beings have the capacity to recognize objects in natural visual scenes with
      high efficiency despite the complexity of such scenes, which usually contain
      multiple objects. One possible mechanism for dealing with this problem is
      selective attention. Psychophysical evidence strongly suggests that selective
      attention can enhance the spatial resolution in the input region corresponding to
      the focus of attention. In this work we adopt a computational neuroscience
      perspective to analyze the attentional enhancement of spatial resolution in the
      area containing the objects of interest. We extend and apply the computational
      model of Deco and Schurmann (2000), which consists of several modules with
      feedforward and feedback interconnections describing the mutual links between
      different areas of the visual cortex. Each module analyses the visual input with
      different spatial resolution and can be thought of as a hierarchical predictor at
      a given level of resolution. Moreover, each hierarchical predictor has a
      submodule that consists of a group of neurons performing a biologically based 2D
      Gabor wavelet transformation at a given resolution level. The attention control
      decides in which local regions the spatial resolution should be enhanced in a
      serial fashion. In this sense, the scene is first analyzed at a coarse resolution
      level, and the focus of attention enhances iteratively the resolution at the
      location of an object until the object is identified. We propose and simulate new
      psychophysical experiments where the effect of the attentional enhancement of
      spatial resolution can be demonstrated by predicting different reaction time
      profiles in visual search experiments where the target and distractors are
      defined at different levels of resolution.

PMID- 11443285
TI  - A laterally interconnected neural architecture in MST accounts for psychophysical
      discrimination of complex motion patterns.
AB  - The complex patterns of visual motion formed across the retina during self
      motion, often referred to as optic flow, provide a rich source of information
      describing our dynamic relationship within the environment. Psychophysical
      studies indicate the existence of specialized detectors for component motion
      patterns (radial, circular, planar) that are consistent with the visual motion
      properties of cells in the medial superior temporal area (MST) of nonhuman
      primates. Here we use computational modeling and psychophysics to investigate the
      structural and functional role of these specialized detectors in performing a
      graded motion pattern (GMP) discrimination task. In the psychophysical task
      perceptual discrimination varied significantly with the type of motion pattern
      presented, suggesting perceptual correlates to the preferred motion bias reported
      in MST. Simulated perceptual discrimination in a population of independent MST
      like neural responses showed inconsistent psychophysical performance that varied
      as a function of the visual motion properties within the population code. Robust
      psychophysical performance was achieved by fully interconnecting neural
      populations such that they inhibited nonpreferred units. Taken together, these
      results suggest that robust processing of the complex motion patterns associated
      with self-motion and optic flow may be mediated by an inhibitory structure of
      neural interactions in MST.

PMID- 11443286
TI  - A model of a segmental oscillator in the leech heartbeat neuronal network.
AB  - We modeled a segmental oscillator of the timing network that paces the heartbeat
      of the leech. This model represents a network of six heart interneurons that
      comprise the basic rhythm-generating network within a single ganglion. This model
      builds on a previous two cell model (Nadim et al., 1995) by incorporating
      modifications of intrinsic and synaptic currents based on the results of a
      realistic waveform voltage-clamp study (Olsen and Calabrese, 1996). Due to these
      modifications, the new model behaves more similarly to the biological system than
      the previous model. For example, the slow-wave oscillation of membrane potential
      that underlies bursting is similar in form and amplitude to that of the
      biological system. Furthermore, the new model with its expanded architecture
      demonstrates how coordinating interneurons contribute to the oscillations within
      a single ganglion, in addition to their role of intersegmental coordination.

PMID- 11443287
TI  - The transient precision of integrate and fire neurons: effect of background
      activity and noise.
AB  - We study the response of an integrate and fire neuron to a randomly timed step
      stimulus. We calculate the latency to the first spike after stimulus onset and
      its jitter. Background activity, seen in most neurons, reduces latency but causes
      substantial jitter in the response, indicating a tradeoff between timing
      precision and latency. The effect of intrinsic noise and synaptic noise on this
      tradeoff is studied. For synaptic noise we find that, unexpectedly, jitter does
      not increase for larger synaptic amplitudes, instead, jitter is practically
      independent of synaptic amplitude. Constant intrinsic noise interacts
      counterintuitively with latency and jitter, and depending on the stimulus
      strength, noise shifts the tradeoff in either direction.

PMID- 11443288
TI  - Localized bumps of activity sustained by inhibition in a two-layer thalamic
      network.
AB  - Based on head direction experiments in rats, the existence of localized bumps of
      thalamic activity has been proposed. We computationally demonstrate the existence
      of a novel class of localized bump solutions in a two-layer conductance-based
      thalamic network and analyze the mechanisms behind these stable patterns. In
      contrast to previous models of bump activity, here inhibition plays a crucial
      role in initially spreading neuronal firing and in subsequently sustaining it. In
      our model, we incorporate local strong, fast GABA(A) inhibition and diffuse weak,
      slow GABA(B) inhibition, based on previous biophysical experiments. These forms
      of inhibition contribute in different, yet complementary, ways to the observed
      pattern formation.

PMID- 11443291
TI  - [Brain sonography in 2001. Evaluation of macrocrania in the infant].
AB  - Transfontanelle sonography has become a routine imaging modality to assess
      infants with macrocrania: detection of hydrocephalus and diagnosis of its
      underlying etiology, detection and mapping of extra-axial collections, value of
      Doppler US for diagnosis of intracranial lesions, hemodynamic evaluation using
      pulsed Doppler imaging.

PMID- 11443292
TI  - [Sonography of thoracic diseases in children].
AB  - This article reviews the major indications for chest sonography in children.
      Sonography should be performed after chest radiographs have been obtained in
      order to assess the need for further imaging with CT and/or MRI. Sonography
      allows accurate assessment of the pleural compartment especially for evaluation
      of pleural effusions, the diaphragm, peripheral lung lesions and anterior, middle
      and postero-inferior mediastinal lesions. Imaging of the thymus is emphasized
      because normal thymus can mimic pathologic situations and tumors may arise within
      the thymus. This technique allows tissue characterization and it is superior to
      other modalities in characterization of fluid. Sonography may be used to guide
      aspirations and biopsies. Sonography of the chest is the modality of choice in
      children because of its lack of ionizing radiation and ease to perform.

PMID- 11443293
TI  - [Sonography of the pediatric abdomen: liver and biliary tract].
AB  - Ultrasound is a routine imaging modality that is quite valuable to assess the
      pediatric abdomen. The objective of this article is to describe the sonographic
      appearance of the liver and bile ducts in children. Our goal is to emphasize
      normal variants and specific pediatric diseases, even if some of them may be
      encountered in adults.

PMID- 11443294
TI  - [Sonography of the pediatric abdomen: pancreas and spleen].
AB  - Ultrasound is a routine imaging modality that is quite valuable to assess the
      pediatric abdomen. The objective of this article is to describe the sonographic
      appearance of the pancreas and spleen in children. Our goal is to emphasize
      normal variants and specific pediatric diseases, even if some of them may be
      encountered in adults.

PMID- 11443295
TI  - [Role of ultrasound in children with emergency gastrointestinal diseases].
AB  - Over the last twenty years, ultrasound has progressively become the primary
      modality used to assess the acute pediatric abdomen. The lack of radiation
      exposure and the high diagnostic efficacy of US have contributed to broaden the
      use of US. During his career, any radiologist may be involved in the evaluation
      of an acute abdomen in a child. He has to be familiar with the sonographic
      findings and the age-related symptoms which allow diagnosis of intussusception,
      hypertrophic pyloric stenosis, midgut volvulus, and appendicitis. He also has to
      be familiar with the findings which help to exclude these diseases. For
      experienced radiologists the accuracy in detecting appendicitis and
      intussusception are respectively close to 95% and 100%. In this chapter, we will
      also discuss the differential diagnoses of the most frequent causes of acute
      pediatric abdomen and the technical limitations of US. The learning objectives
      will be

PMID- 11443296
TI  - [Ultrasound in pediatric urology].
AB  - GENERAL OBJECTIVE: To review technical considerations, indications, findings and
      limitations of ultrasound and Doppler in pediatric urology. EDUCATIONAL
      OBJECTIVES: This course aims to help the reader improve his/her own technical
      skills and knowledge of ultrasound findings as well as their significance in
      pediatric urology. The most common causes of misinterpretation and limitations
      are reviewed. The scope of the article is limited to common diseases: infection,
      urinary tract malformation, trauma and tumor. Because ultrasound cannot be
      separated from other imaging modalities, the indications for each of these
      imaging modalities are provided in relevant sections.

PMID- 11443297
TI  - [Echography of the hip and other imaging techniques in pediatrics].
AB  - OBJECTIVES: To standardize the ultrasound evaluation in congenital hip dysplasia
      according to the consensus meeting of 1991 in Paris. Detection of congenital
      anomalies is a daily pediatric challenge. The coronal plane at US of the hip is
      considered as the gold standard: its technique, its morphologic and dynamic
      results either normal or pathological, have been described. A standardized report
      and a simple terminology are proposed. 2. To explain the role of ultrasound, when
      performed in close collaboration with a pediatric orthopedic surgeon, for initial
      diagnosis and follow-up of anatomical anomalies. The role of arthrography and MR
      imaging will be discussed. 3. To describe the benefit of the ultrasound in cases
      of painful hip in children, including osteoarthritis, acute synovitis,
      osteochondritis. . . In these cases, the assessment of the hip is also done with
      radiographs, computer tomography, MR imaging and bone scan.

PMID- 11443298
TI  - Increased efficiency of mRNA 3' end formation: a new genetic mechanism
      contributing to hereditary thrombophilia.
AB  - The G-->A mutation at position 20210 of the prothrombin or coagulation factor II
      gene (F2) represents a common genetic risk factor for the occurrence of
      thromboembolic events. This mutation affects the 3'-terminal nucleotide of the 3'
      untranslated region (UTR) of the mRNA and causes elevated prothrombin plasma
      concentrations by an unknown mechanism. Here, we show that the mutation does not
      affect the amount of pre-mRNA, the site of 3' end cleavage or the length of the
      poly(A) tail of the mature mRNA. Rather, we demonstrate that the physiological F2
      3' end cleavage signal is inefficient and that F2 20210 G-->A represents a gain
      of-function mutation, causing increased cleavage site recognition, increased 3'
      end processing and increased mRNA accumulation and protein synthesis. Enhanced
      mRNA 3' end formation efficiency emerges as a novel principle causing a genetic
      disorder and explains the role of the F2 20210 G-->A mutation in the pathogenesis
      of thrombophilia. This work also illustrates the pathophysiologic importance of
      quantitatively minor aberrations of RNA metabolism.

PMID- 11443299
TI  - Experimentally-derived haplotypes substantially increase the efficiency of
      linkage disequilibrium studies.
AB  - The study of complex genetic traits in humans is limited by the expense and
      difficulty of ascertaining populations of sufficient sample size to detect subtle
      genetic contributions to disease. Here we introduce an application of a somatic
      cell hybrid construction strategy called conversion that maximizes the genotypic
      information from each sampled individual. The approach permits direct observation
      of individual haplotypes, thereby eliminating the need for collecting and
      genotyping DNA from family members for haplotype-based analyses. We describe
      experimental data that validate the use of conversion as a whole-genome
      haplotyping tool and evaluate the theoretical efficiency of using conversion
      derived haplotypes instead of conventional genotypes in the context of haplotype
      frequency estimation. We show that, particularly when phenotyping is expensive,
      conversion-based haplotyping can be more efficient and cost-effective than
      standard genotyping.

PMID- 11443300
TI  - Acute fatal poisoning by methomyl caused by inhalation and transdermal
      absorption.

PMID- 11443301
TI  - Contamination of medicinal herbs with organophosphorus insecticides.

PMID- 11443302
TI  - Estimation of Co and Mn in some medicinal plants.

PMID- 11443303
TI  - Exposure to nitrogen dioxide in buses, taxis, and bicycles in Perth, Western
      Australia.

PMID- 11443304
TI  - Blood mercury concentrations in the population of Rabat area, Morocco.

PMID- 11443305
TI  - Heavy metals in human hair related to age groups and automotive pollution levels
      of Bandarlampung City, Indonesia.

PMID- 11443306
TI  - Micronucleus frequency in cytokinesis-blocked bovine lymphocytes from regions
      with different pollution levels in Slovakia.

PMID- 11443307
TI  - Determination of dialkyl phthalates in high altitude atmosphere for validation of
      sampling method using a helicopter.

PMID- 11443308
TI  - Genotoxicity testing of some metals in the Drosophila wing somatic mutation and
      recombination test.

PMID- 11443309
TI  - Monitoring stream water quality with mouse cell culture and on-site allium tests.

PMID- 11443310
TI  - Biochemical biomarkers in fish from different river systems reflect exposure to a
      variety of anthropogenic stressors.

PMID- 11443311
TI  - Influence of food-capture nets on cadmium uptake by net-spinning caddisfly
      (Trichoptera: Hydropsychidae) larvae.

PMID- 11443312
TI  - Organochlorine residue sequestration by Anopheles culicifacies sensu lato
      mosquito larvae.

PMID- 11443313
TI  - PCBs in three predatory birds from Galicia (NW Spain).

PMID- 11443314
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in surface sediments from
      Pearl River Delta in China.

PMID- 11443315
TI  - Distribution of polychlorinated biphenyls in the Bering and Chukchi Sea.

PMID- 11443316
TI  - Influence of soil aggregate size on atrazine and trifluralin leaching.

PMID- 11443317
TI  - Microalgae in petrochemical effluent: growth and biosorption of total dissolved
      solids.

PMID- 11443318
TI  - Parasitism and phagocytic function among sand lance Ammodytes hexapterus Pallas
      exposed to crude oil-laden sediments.

PMID- 11443319
TI  - Acute toxicity of 33 herbicides to the green alga Chlorella pyrenoidosa.

PMID- 11443320
TI  - Heavy metal resistance Chlorella spp., isolated from tannery effluents, and their
      role in remediation of hexavalent chromium in industrial waste water.

PMID- 11443321
TI  - Ecotoxicological study of the Niger-Delta area of the River Niger.

PMID- 11443322
TI  - Monitoring granular terbufos breakthrough: comparison of cotton gauze and alpha
      cellulose.

PMID- 11443323
TI  - Potentially toxic colorant precursors and preservatives used in finger-paints.

PMID- 11443324
TI  - Pulmonary histopathology in ring-billed gulls (Larus delawarensis) from colonies
      near steel mills and in rural areas.

PMID- 11443325
TI  - Utilization of Odontesthes regia (Atherinidae) from the south eastern Pacific as
      a test organism for bioassays: study of its sensitivity to six chemicals.

PMID- 11443326
TI  - Biomarkers of oxidative stress in the polychaete Eurythoe complanata
      (Amphinomidae) under short term copper exposure.

PMID- 11443327
TI  - Biochemical biomarker responses and chlorinated compounds in the fish Leusciscus
      cephalus along a contaminant gradient in a polluted river.

PMID- 11443328
TI  - Effects of 17-beta estradiol exposure on metallothionein and fat soluble
      antioxidant vitamins in juvenile lake trout (Salvelinus namaycush).

PMID- 11443329
TI  - Toxicokinetics and acute toxicity of waterborne zinc in abalone (Haliotis
      diversicolor supertexta Lischke).

PMID- 11443330
TI  - Comparison of acetylcholinesterase and glutathione S-transferase activity in
      Chironomus riparius Meigen exposed to chemical-spiked sediments.

PMID- 11443331
TI  - Influence of protective agents on metal induced respiratory distress in Labeo
      rohita (Ham).

PMID- 11443332
TI  - Impact of distillery effluent on physiological consequences in the freshwater
      teleost Channa punctatus.

PMID- 11443333
TI  - Growth and cytology of Chlamydomonas acidophila under acidic stress.

PMID- 11443334
TI  - Bioaccumulation of mercury by Tucunare (Cichla ocellaris) from Tapajos River
      region, Brazilian Amazon: a field dose-response approach.

PMID- 11443335
TI  - Mercury concentrations in yellow perch (Perca flavescens) from Vilas County,
      Wisconsin: 1920s versus 1980s.

PMID- 11443336
TI  - Hydrocarbon pollution in the Arabian Gulf catfish (Arius bilineatus Val.).

PMID- 11443337
TI  - Occurrence of herbicides and their degradates in Hawaii's groundwater.

PMID- 11443338
TI  - Residual fate of metribuzin on carrot (Daucus carota) crop.

PMID- 11443339
TI  - Influence of the formulation on the sorption and the mobility of diuron in soil.

PMID- 11443340
TI  - Disappearance of polychlorinated biphenyls (PCBs) when incubated with tissue
      cultures of different plant species.

PMID- 11443341
TI  - Organochlorine insecticide residues in dairy milk samples collected in Lucknow,
      India.

PMID- 11443342
TI  - Application of photoacoustic spectroscopy in studies of environment contamination
      effect on needles of Scots pine (Pinus silvestris L.).

PMID- 11443343
TI  - A phylogenetic framework for the aquaporin family in eukaryotes.
AB  - A comprehensive evolutionary analysis of aquaporins, a family of intrinsic
      membrane proteins that function as water channels, was conducted to establish
      groups of homology (i.e., to identify orthologues and paralogues) within the
      family and to gain insights into the functional constraints acting on the
      structure of the aquaporin molecule structure. Aquaporins are present in all
      living organisms, and therefore, they provide an excellent opportunity to further
      our understanding of the broader biological significance of molecular evolution
      by gene duplication followed by functional and structural specialization. Based
      on the resulting phylogeny, the 153 channel proteins analyzed were classified
      into six major paralogous groups: (1) GLPs, or glycerol-transporting channel
      proteins, which include mammalian AQP3, AQP7, and AQP9, several nematode
      paralogues, a yeast paralogue, and Escherichia coli GLP; (2) AQPs, or aquaporins,
      which include metazoan AQP0, AQP1, AQP2, AQP4, AQP5, and AQP6; (3) PIPs, or
      plasma membrane intrinsic proteins of plants, which include PIP1 and PIP2; (4)
      TIPs, or tonoplast intrinsic proteins of plants, which include alphaTIP,
      gammaTIP, and deltaTIP; (5) NODs, or nodulins of plants; and (6) AQP8s, or
      metazoan aquaporin 8 proteins. Of these groups, AQPs, PIPs, and TIPs cluster
      together. According to the results, the capacity to transport glycerol shown by
      several members of the family was acquired only early in the history of the
      family. The new phylogeny reveals that several water channel proteins are
      misclassified and require reassignment, whereas several previously undetermined
      ones can now be classified with confidence. The deduced phylogenetic framework
      was used to characterize the molecular features of water channel proteins. Three
      motifs are common to all family members: AEF (Ala-Glu-Phe), which is located in
      the N-terminal domain; and two NPA (Asp-Pro-Ala) boxes, which are located in the
      center and C-terminal domains, respectively. Other residues are found to be
      conserved within the major groups but not among them. Overall, the PIP subfamily
      showed the least variation. In general, no radical amino acid replacements
      affecting tertiary structure were identified, with the exception of Ala-->Ser in
      the TIP subfamily. Constancy of rates of evolution was demonstrated within the
      different paralogues but rejected among several of them (GLP and NOD).

PMID- 11443344
TI  - Phylogenetic analysis of evolutionary relationships of the planctomycete division
      of the domain bacteria based on amino acid sequences of elongation factor Tu.
AB  - Sequences from the tuf gene coding for the elongation factor EF-Tu were amplified
      and sequenced from the genomic DNA of Pirellula marina and Isosphaera pallida,
      two species of bacteria within the order Planctomycetales. A near-complete (1140
      bp) sequence was obtained from Pi. marina and a partial (759-bp) sequence was
      obtained for I. pallida. Alignment of the deduced Pi. marina EF-Tu amino acid
      sequence against reference sequences demonstrated the presence of a unique 11
      amino acid sequence motif not present in any other division of the domain
      Bacteria. Pi. marina shared the highest percentage amino acid sequence identity
      with I. pallida but showed only a low percentage identity with other members of
      the domain Bacteria. This is consistent with the concept of the planctomycetes as
      a unique division of the Bacteria. Neither primary sequence comparison of EF-Tu
      nor phylogenetic analysis supports any close relationship between planctomycetes
      and the chlamydiae, which has previously been postulated on the basis of 16S
      rRNA. Phylogenetic analysis of aligned EF-Tu amino acid sequences performed using
      distance, maximum-parsimony, and maximum-likelihood approaches yielded
      contradictory results with respect to the position of planctomycetes relative to
      other bacteria. It is hypothesized that long-branch attraction effects due to
      unequal evolutionary rates and mutational saturation effects may account for some
      of the contradictions.

PMID- 11443345
TI  - Poxviruses and the origin of the eukaryotic nucleus.
AB  - A number of molecular forms of DNA polymerases have been reported to be involved
      in eukaryotic nuclear DNA replication, with contributions from alpha-, delta-,
      and epsilon-polymerases. It has been reported that delta-polymerase possessed a
      central role in DNA replication in archaea, whose ancestry are thought to be
      closely related to the ancestor of eukaryotes. Indeed, in vitro experiment shown
      here suggests that delta-polymerase has the potential ability to start DNA
      synthesis immediately after RNA primer synthesis. Therefore, the question arises,
      where did the alpha-polymerase come from? Phylogenetic analysis based on the
      nucleotide sequence of several conserved regions reveals that two poxviruses,
      vaccinia and variola viruses, have polymerases similar to eukaryotic alpha
      polymerase rather than delta-polymerase, while adenovirus, herpes family viruses,
      and archaeotes have eukaryotic delta-like polymerases, suggesting that the
      eukaryotic alpha-polymerase gene is derived from a poxvirus-like organism, which
      had some eukaryote-like characteristics. Furthermore, the poxvirus's
      proliferation independent from the host-cell nucleus suggests the possibility
      that this virus could infect non-nucleated cells, such as ancestral eukaryotes. I
      wish to propose here a new hypothesis for the origin of the eukaryotic nucleus,
      posing symbiotic contact of an orthopoxvirus ancestor with an archaebacterium,
      whose genome already had a delta-like polymerase gene.

PMID- 11443346
TI  - Evolution rates of genes on leading and lagging DNA strands.
AB  - One of the main causes of bacterial chromosome asymmetry is replication
      associated mutational pressure. Different rates of nucleotide substitution
      accumulation on leading and lagging strands implicate qualitative and
      quantitative differences in the accumulation of mutations in protein coding
      sequences lying on different DNA strands. We show that the divergence rate of
      orthologs situated on leading strands is lower than the divergence rate of those
      situated on lagging strands. The ratio of the mutation accumulation rate for
      sequences lying on lagging strands to that of sequences lying on leading strands
      is rather stable and time-independent. The divergence rate of sequences which
      changed their positions, with respect to the direction of replication fork
      movement, is not stable-sequences which have recently changed their positions are
      the most prone to mutation accumulation. This effect may influence estimations of
      evolutionary distances between species and the topology of phylogenetic trees.

PMID- 11443347
TI  - The effect of branch length variation on the selection of models of molecular
      evolution.
AB  - Models of sequence evolution play an important role in molecular evolutionary
      studies. The use of inappropriate models of evolution may bias the results of the
      analysis and lead to erroneous conclusions. Several procedures for selecting the
      best-fit model of evolution for the data at hand have been proposed, like the
      likelihood ratio test (LRT) and the Akaike (AIC) and Bayesian (BIC) information
      criteria. The relative performance of these model-selecting algorithms has not
      yet been studied under a range of different model trees. In this study, the
      influence of branch length variation upon model selection is characterized. This
      is done by simulating sequence alignments under a known model of nucleotide
      substitution, and recording how often this true model is recovered by different
      model-fitting strategies. Results of this study agree with previous simulations
      and suggest that model selection is reasonably accurate. However, different model
      selection methods showed distinct levels of accuracy. Some LRT approaches showed
      better performance than the AIC or BIC information criteria. Within the LRTs,
      model selection is affected by the complexity of the initial model selected for
      the comparisons, and only slightly by the order in which different parameters are
      added to the model. A specific hierarchy of LRTs, which starts from a simple
      model of evolution, performed overall better than other possible LRT hierarchies,
      or than the AIC or BIC.

PMID- 11443348
TI  - The structure and evolution of Penelope in the virilis species group of
      Drosophila: an ancient lineage of retroelements.
AB  - The Penelope element is the key element responsible for mobilization of other
      transposable elements in the course of hybrid dysgenesis in Drosophila virilis.
      Penelope has an unusually complex, highly variable organization in all studied
      species of the virlis group. Thc BRIDGE1 element from the fish Fugu rubripes is
      homologous to Penelope, and database searches detected additional homologous
      sequences among Expressed Sequence Tags from the flatworm Schistosoma mansonii
      and the nematode Ancylostoma caninum. Phylogenetic analysis shows that the
      reverse transcriptase of the Penelope group does not belong to any of the
      characterized major retroelement lineages, but apparently represents a novel
      branch of non-LTR retroelements. Sequence profile analysis results in the
      prediction that the C-terminal domain of the Penelope polyprotein is an active
      endonuclease related to intron-encoded endonucleases and the bacterial repair
      endonuclease UvrC, which could function as an integrase. No retroelements
      containing a predicted endonuclease of this family have been described
      previously. Phylogenetic analysis of Penelope copies isolated from several
      species of the virilis group reveals two subfamilies of Penelope elements, one of
      which includes full-length copies whose nucleotide sequences are almost
      identical, whereas the other one consists of highly diverged defective copies.
      Phylogenetic analysis of Penelope suggests both vertical transmission of the
      element and probable horizontal transfers. These findings support the notion that
      Penelope invasions occurred repeatedly in the evolution of the virilis group.

PMID- 11443349
TI  - Enzymic and structural studies on Drosophila alcohol dehydrogenase and other
      short-chain dehydrogenases/reductases.
AB  - Enzymic and structural studies on Drosophila alcohol dehydrogenases and other
      short-chain dehydrogenases/reductases (SDRs) are presented. Like alcohol
      dehydrogenases from other Drosophila species, the enzyme from D. simulans is more
      active on secondary than on primary alcohols, although ethanol is its only known
      physiological substrate. Several secondary alcohols were used to determine the
      kinetic parameters kcat and Km. The results of these experiments indicate that
      the substrate-binding region of the enzyme allows optimal binding of a short
      ethyl side-chain in a small binding pocket, and of a propyl or butyl side-chain
      in large binding pocket, with stereospecificity for R(-) alcohols. At a high
      concentration of R(-) alcohols substrate activation occurs. The kcat and Km
      values determined under these conditions are about two-fold, and two orders of
      magnitude, respectively, higher than those at low substrate concentrations.
      Sequence alignment of several SDRs of known, and unknown three-dimensional
      structures, indicate the presence of several conserved residues in addition to
      those involved in the catalyzed reactions. Structural roles of these conserved
      residues could be derived from observations made on superpositioned structures of
      several SDRs with known structures. Several residues are conserved in tetrameric
      SDRs, but not in dimeric ones. Two halohydrin-halide-lyases show significant
      homology with SDRs in the catalytic domains of these enzymes, but they do not
      have the structural features required for binding NAD+. Probably these lyases
      descend from an SDR, which has lost the capability to bind NAD+, but the enzyme
      reaction mechanisms may still be similar.

PMID- 11443350
TI  - A test of amino acid reversibility.
AB  - In studies of molecular evolution, the assumption that protein evolution is
      reversible has often been made, but rarely tested. Here we use a large set of
      orthologous murid protein coding sequences to perform a simple test of
      reversibility, and find no evidence to reject the assumption of reversibility in
      protein evolution.

PMID- 11443351
TI  - Phylogenetic analysis of metabolic pathways.
AB  - The information provided by completely sequenced genomes can yield insights into
      the multi-level organization of organisms and their evolution. At the lowest
      level of molecular organization individual enzymes are formed, often through
      assembly of multiple polypeptides. At a higher level, sets of enzymes group into
      metabolic networks. Much has been learned about the relationship of species from
      phylogenetic trees comparing individual enzymes. In this article we extend
      conventional phylogenetic analysis of individual enzymes in different organisms
      to the organisms' metabolic networks. For this purpose we suggest a method that
      combines sequence information with information about the underlying reaction
      networks. A distance between pathways is defined as incorporating distances
      between substrates and distances between corresponding enzymes. The new analysis
      is applied to electron-transfer and amino acid biosynthesis networks yielding a
      more comprehensive understanding of similarities and differences between
      organisms.

PMID- 11443352
TI  - Molecular chaperones encoded by a reduced nucleus: the cryptomonad nucleomorph.
AB  - Molecular chaperones mediate the correct folding of nascent or denatured proteins
      and are found in both the organelles and cytoplasm of eukaryotic cells.
      Cryptomonad algae are unusual in possessing an extra cytoplasmic compartment (the
      periplastid space), the result of having engulfed and retained a photosynthetic
      eukaryote. Within the periplastid space is a diminutive nucleus (the nucleomorph)
      that encodes mostly genes for its own expression as well as a few needed by the
      plastid. Two plastid-encoded chaperones (GroEL and DnaK) and a nucleomorph
      encoded chaperone (Cpn60) have been reported from the cryptomonad, Guillardia
      theta. Here we analyse G. theta nucleomorph genes for members of the cytosolic
      HSP70 and HSP90 families of molecular chaperones, a heat shock transcription
      factor (HSF), and all eight subunits of the group II chaperonin, CCT. These are
      presumably all active in the periplastid space, assisting in the maturation of
      polypeptides required by the cell; we propose a central role for them also in the
      structure and assembly of a putative relict mitotic apparatus. Curiously, none of
      the genes for co-chaperones of HSP70, HSP90, or CCT have been detected in the
      nucleomorph genome; they are either not needed or are encoded in the host nuclear
      genome and targeted back into the periplastid space. Endoplasmic reticulum (ER)
      homologs of HSP70 and HSP90 are also not present. Striking differences in the
      degree of conservation of the various nucleomorph-encoded molecular chaperones
      were observed. While the G. theta HSP70 and HSP90 homologs are well conserved,
      each of the eight CCT subunits (alpha, beta, gamma, delta, epsilon, eta, theta,
      and zeta) is remarkably divergent. Such differences are likely evidence for
      reduced/different functional constraints on the various molecular chaperones
      functioning in the periplastid space.

PMID- 11443353
TI  - Plasticity of fitness and diversification process during an experimental
      molecular evolution.
AB  - A simplified experimental evolution encompassing the essence of natural one was
      designed in an attempt to understand the involved mechanism. In our system,
      molecular evolution was observed through three serial cycles of consecutive
      random mutagenesis of the glutamine synthetase gene and chemostat culture of the
      transformed Escherichia coli cells containing the mutated genes. Selection
      pressure was imposed solely on the glutamine synthetase gene when varieties of
      mutant genes compete in an unstructured environment of the chemostat. The
      molecular phylogeny and population dynamics were deduced from the nucleotide
      sequences of the genes isolated from each of the chemostat runs. An initial
      mutant population in each cycle, comprised of diversified closely-related genes,
      ended up with several varieties of mutants in a state of coexistence. Competition
      between two mutant genes in the final population of the first cycle ascertained
      that the observed coexisting state is not an incidental event and that cellular
      interaction via environmental nutrients is a possible mechanism of coexistence.
      In addition, the mutant gene once extinct in the previous passage was found to
      have the capacity to reinvade and constitute the gene pool of the later cycle of
      molecular evolution. These results, including the kinetic characteristics of the
      purified wild-type and mutant glutamine synthetases in the phylogenetic tree,
      revealed that the enzyme activity had diverged, rather than optimized, to a
      fittest value during the course of evolution. Here, we proposed that the
      plasticity of gene fitness in consequence of cellular interaction via the
      environment is an essential mechanism governing molecular evolution.

PMID- 11443354
TI  - The evolution of an alternatively spliced exon in the alphaA-crystallin gene.
AB  - The evolutionary aspects of alternative splicing, as a mechanism to increase the
      diversity of gene products, are poorly understood. Here we analyse the evolution
      of a 69-bp exon that is alternatively spliced in the primary transcript of the
      gene for the mammalian eye lens protein alphaA-crystallin. In rodents, the
      skipping of this exon 2 is attributed to the presence of a non-consensus 5'
      splice site GC, and results in the expression of 10-20% of alphaA(ins)
      crystallin, with an insert of 23 residues, as compared with normal alphaA
      crystallin. alphaA(ins)-crystallin is also expressed in some non-rodent mammals,
      including kangaroo, while lacking in others. We now demonstrate that the
      alternatively spliced exon 2 is present in mammals from different orders that do
      not express alphaA(ins)-crystallin. The expression of this exon has thus been
      silenced independently in various lineages. Sequence comparison in 16 species
      reveals that--whether or not alphaA(ins)-crystallin is expressed--exon 2 is
      always flanked by the non-consensus donor splice site GC, while a consensus
      branch point sequence and 3' pyrimidine-rich region are hardly detectable in the
      downstream intron. Increased numbers of amino acid replacements in the peptide
      encoded by exon 2 indicate that it is subject to much lower selective constraints
      than the exons that code for normal alphaA-crystallin. The absence of any
      apparent advantage at the protein level may suggest that exon 2 DNA sequences are
      conserved as cis-acting factors for proper splicing of the alphaA-crystallin
      transcript.

PMID- 11443355
TI  - Genetic divergence of orangutan subspecies (Pongo pygmaeus).
AB  - Microsatellites and mitochondrial DNA sequences were studied for the two
      subspecies of orangutans (Pongo pygmaeus), which are located in Borneo (P. p.
      pygmaeus) and Sumatra (P. p. abelii), respectively. Both subspecies possess
      marked genetic diversity. Genetic subdivision was identified within the Sumatran
      orangutans. The genetic differentiation between the two subspecies is highly
      significant for ND5 region but not significant for 16s rRNA or microsatellite
      data by exact tests, although FST estimates are highly significant for these
      markers. Divergence time between the two subspecies is approximately 2.3 +/- 0.5
      million years ago (MYA) estimated from our data, much earlier than the isolation
      of their geological distribution. Neither subspecies underwent a recent
      bottleneck, though the Sumatran subspecies might have experienced expansion
      approximately 82,000 years ago. The estimated effective population sizes for both
      subspecies are on the order of 104. Our results contribute additional information
      that may be interpreted in the context of orangutan conservation efforts.

PMID- 11443356
TI  - Are red algae plants? A critical evaluation of three key molecular data sets.
AB  - Whether red algae are related to green plants has been debated for over a
      century. Features present due to their shared photosynthetic habit have been
      interpreted as support for an evolutionary sisterhood of the two groups but,
      until very recently, characters endogenous to the host cell have provided no
      reliable indication of such a relationship. In this investigation, we examine
      three molecular data sets that have provided key evidence of a possible
      relationship between green plants and red algae. Analyses of an expanded
      alignment of DNA-dependent RNA polymerase II largest subunit sequences indicate
      that their support for independent origins of rhodophytes and chlorophytes is not
      the result of long-branch attraction, as has been proposed elsewhere. Differences
      in the pol II C-terminal domain, an essential component of plant mRNA
      transcription, also suggest different host cell ancestors for the two groups. In
      contrast, concatenated sequences of two groups of mitochondrial genes, those
      encoding subunits of NADH-dehydrogenase as well as cytochrome c oxidase subunits
      plus apocytochrome B, appear to cluster red algal and green plant sequences
      together because both groups have evolved relatively slowly and share a super
      abundance of ancestral positions. Finally, analyses of elongation factor 2
      sequences demonstrate a strong phylogenetic signal favoring a
      rhodophyte/chlorophyte sister relationship, but that signal is restricted to a
      contiguous segment comprising approximately half of the EF2 gene. These results
      argue for great caution in the interpretation of phylogenetic analyses of ancient
      evolutionary events but, in combination, indicate that there is no emerging
      consensus from molecular data supporting a sister relationship between red algae
      and green plants.

PMID- 11443357
TI  - The closest BLAST hit is often not the nearest neighbor.
AB  - It is well known that basing phylogenetic reconstructions on uncorrected genetic
      distances can lead to errors in their reconstruction. Nevertheless, it is often
      common practice to report simply the most similar BLAST (Altschul et al. 1997)
      hit in genomic reports that discuss many genes (Ruepp et al. 2000; Freiberg et
      al. 1997). This is because BLAST hits can provide a rapid, efficient, and concise
      analysis of many genes at once. These hits are often interpreted to imply that
      the gene is most closely related to the gene or protein in the databases that
      returned the closest BLAST hit. Though these two may coincide, for many genes,
      particularly genes with few homologs, they may not be the same. There are a
      number of circumstances that can account for such limitations in accuracy (Eisen
      2000). We stress here that genes appearing to be the most similar based on BLAST
      hits are often not each others closest relative phylogenetically. The extent to
      which this occurs depends on the availability of close relatives present in the
      databases. As an example we have chosen the analysis of the genomes of a
      crenarcheaota species Aeropyrum pernix, an organism with few close relatives
      fully sequenced, and Escherichia coli, an organism whose closest relative,
      Salmonella typhimurium, is completely sequenced.

PMID- 11443358
TI  - Transformation pathways of 14c-chlorothalonil in tropical soils.
AB  - Chlorothalonil (CTN) is a chlorinated wide-spectrum fungicide, heavily and widely
      applied throughout the world. This study was undertaken to directly evaluate the
      rates and forms of 14C-labeled CTN dissipation in three acid Brazilian soils
      (Typic Humaquept [GH], Typic Quartzipsamment [AQ], and Typic Hapludox [LE]).
      Mineralization was not the major metabolic pathway of CTN-degrading
      microorganisms. However, CTN dissipation was fast in all soils and was mainly due
      to biodegradation (responsible for 50%, 54%, and 73% of 14C-CTN dissipation in
      the GH, LE, and AQ soils, respectively), as well as to formation of soil-bound
      14C residues (responsible for 46%, 34%, and 18% of 14C-CTN dissipation in the GH,
      LE, and AQ soils, respectively). Most soil-bound 14C residues were formed in the
      first day, but aging also contributed to the formation of less reversible forms
      of CTN-soil complexes. In these acid soils, the most abundant metabolite formed
      from CTN degradation was 3-carbamyl-2,4,5-trichlorobenzoic acid. A significant
      fraction of the CTN that had been assumed to be rapidly degradable in soils in
      previous reports has turned out to be soil-bound residues. Although
      bioavailability of any compound is reduced when soil complexes are formed,
      further research is needed to evaluate accumulation and availability of CTN soil
      bound residues over long-term applications, and the consequent detrimental
      effects on the environment and on soil quality and fertility.

PMID- 11443359
TI  - The evaluation of metal retention by a constructed wetland using the pulmonate
      gastropod Helisoma trivolvis (Say).
AB  - Constructed wetlands are built because they can act as sinks for many pollutants,
      thereby protecting the water quality of downstream ecosystems. The treatment
      performance is generally assessed using mass balance calculations. Along with the
      mass balance approach, we compared the metal content of populations of a common
      pond snail (Helisoma trivolvis Say) collected upstream and downstream of a 3-year
      old constructed wetland. Snails were collected in early May, June, and August
      1998. At the same time, water samples for particulate and dissolved metals were
      taken every 3 days for the duration of the experiment. Overall, the wetland
      retained most dissolved metals, including Fe, Mn, Cu, Zn, Ni, and Pb, but
      released dissolved As. However, the wetland released particulate Fe and Mn. With
      the exception of Zn, the metal concentrations of the downstream snails were on
      average higher than those measured in the upstream population. The higher metal
      content of downstream snails was likely related to the significant export of
      particulate metals by the wetland, despite the overall retention of dissolved
      metals. This study points to the need for biological as well as chemical
      monitoring to determine the treatment efficiency and toxicological risk
      associated with constructed wetlands.

PMID- 11443360
TI  - Immunotoxicity of explosives-contaminated soil before and after bioremediation.
AB  - Soils from the Yorktown Naval Base contaminated with trinitrotoluene (TNT) and
      other explosives were used to prepare eluates before and after bioremediation
      using microbial growth amendments in the presence (P1 eluates) or absence (P2
      eluates) of exogenous white rot fungus. Effectiveness of bioremediation was
      examined by several immunotoxicity assays-viability/growth of lymphocytes,
      cytokine production, and expression of the interleukin-2 (IL-2) receptor-using
      human peripheral blood mononuclear cells exposed to the eluates. Although TNT
      concentrations decreased in both P1 and P2 eluates relative to untreated baseline
      soil (BL) eluates, a recovery in lymphocyte growth/viability and IL-2 secretion
      was seen with P2 but not P1 eluates relative to BL eluates. IL-2 receptor levels
      were higher in cells exposed to BL and P2 eluates than when exposed to P1
      eluates. Interferon-gamma, tumor necrosis factor-beta, and IL-10 levels were
      highest in BL and P2 eluates and lowest in P1 eluates. Taken together, these
      results suggest that treatment of the soil with microbial growth amendments in
      the absence but not the presence of exogenous white rot fungi lead to partial
      bioremediation as assessed by lymphocyte functions.

PMID- 11443361
TI  - Toxicity of freshwater sediments in the vicinity of an old sawmill: application
      of three bioassays.
AB  - Toxicity of contaminated sediments collected from an old sawmill area and the
      downstream river-lake system was assessed with three different bioassays.
      Survival and growth were used as endpoints in subchronic (10-day) test with
      Chironomus riparius and growth and reproduction in long-term (28-day) test with
      Lumbriculus variegatus. A microbial bioluminescent direct contact assay, the
      Flash test, was also included in the test set to measure acute toxicity. In every
      bioassay, sediment from a pool of the sawmill was found to be toxic, and some
      adverse effects were found in other sediments as well. The bioassays were then
      compared to chemical analysis results, which showed the presence of several
      toxicants. These results could not, however, be directly connected to any
      individual toxicant, nor did they show any obvious trend downstream from the
      mill.

PMID- 11443362
TI  - Influence of aqueous sediment extracts from the Oder River (Germany/Poland) on
      survival of Diplostomum sp. (Trematoda: Diplostomidae) cercariae.
AB  - Laboratory experiments were carried out to test whether the life span of
      Diplostomum sp. cercariae is affected by contamination of its aquatic
      environment. Freshly emerged cercariae therefore were exposed to either
      standardized water, Oder River (Germany/Poland) or Lake Odersee (Germany)
      extracts of aqueous sediments; mortality patterns and mean survival times (MSTs)
      were compared. Cercariae added to extracts of aqueous sediments from the Oder
      River and Lake Odersee exhibited impaired survival with significantly different
      mortality pattern and reduced MST compared to that of controls. A significant
      negative correlation (r = -0.843, p < 0.05) was found between MST and mercury
      content of sediments, indicating a potential impact of mercury on survival of
      Diplostomum sp. cercariae. The results indicate that contamination of freshwater
      habitats may influence the viability of free-living transmission stages of
      helminth parasites of fish and may thus be of epizootiological significance.

PMID- 11443363
TI  - Effects of dissolved organic material on binding and toxicokinetics of pyrene in
      the waterflea Daphnia magna.
AB  - The binding and bioavailability of pyrene was studied in the laboratory in two
      humic fresh waters and in a reference water without dissolved organic material
      (DOM), measured as dissolved organic carbon (DOC). The uptake of pyrene by
      Daphnia magna in short-term (24 h) accumulation experiments was fitted to a first
      order rate-kinetic equation to calculate simultaneous uptake and elimination
      rates. The partition coefficients of pyrene to DOC (KDOC) were 37.1 x 103 in
      Pielisjoki River (9.4 mg DOC L(-1)), and 34.9 x 103 in Lake Kontiolampi (17.4 mg
      DOC L(-1)) waters, indicating similar binding affinities of pyrene for both humic
      waters. The uptake clearance of pyrene (ku) in the DOC-rich Lake Kontiolampi
      water was 290.4 ml g wet weight(-1) h(-1), which was lower than those in
      Pielisjoki River and DOC-free waters (395.8 and 346.0 ml g wet weight(-1) h(-1),
      respectively). Pyrene elimination (ke) was in average 0.2 h(-1) with no
      significant differences between the waters. The observed bioconcentration factors
      of pyrene in Pielisjoki River and Lake Kontiolampi waters were 84% and 46% of
      that in the DOC-free reference water, respectively, thus indicating that a high
      concentration of DOC is needed to decrease the bioavailability of waterborne
      pyrene to D. magna.

PMID- 11443364
TI  - Accumulation of 109Cd by second-generation chironominae propagated from wild
      populations sampled from low-, mid-, and high-saline environments.
AB  - Our objective was to determine if second-generation (F2) chironomids propagated
      from adults of larvae sampled from low-, mid-, and high-saline environments
      differed in their ability to accumulate cadmium from their environment. Second
      generation chironomids cultured from wild populations were exposed to 109Cd at 0,
      0.7, and 4.3 ppt salinity for 10 days, at which time survival and amounts of
      109Cd accumulated were determined. Cultures included two of Chironomus tentans
      from a freshwater lake (lake 78; 0 ppt), and the euryhaline C. athalassicus from
      a mid- (lake 71; 0.7 ppt) and high (lake 56; 4.3 ppt)-saline environment. A
      laboratory-reared culture of C. tentans was included as a positive control.
      Species-dependent accumulation of 109Cd occurred; second-generation C.
      athalassicus cultured from the high-salinity lake survived in the three
      salinities and accumulated significantly greater amounts of the radiotracer at 0
      and 0.7 ppt compared to the second-generation freshwater species, C. tentans.
      Second-generation C. athalassicus cultured from lake 71 also survived all
      salinities with 109Cd accumulation tending to be greater than the freshwater
      species at the mid-salinity range. In contrast, the freshwater species cultured
      from lake 78 as well as the laboratory-reared culture did not survive the highest
      salinity of 4.3 ppt and accumulated less 109Cd compared to the species from the
      high-saline environments. Species-dependent differences in metal accumulation
      need to be considered in studies that assess metal concentrations in aquatic
      organisms across an environmental gradient, such as salinity.

PMID- 11443365
TI  - Toxicity and bioaccumulation of arsenic and chromium in epigean and hypogean
      freshwater macroinvertebrates.
AB  - Lethal toxicity levels of two inorganic water pollutants, chromium (Cr6+) and
      arsenic (As3+), were determined toward six freshwater macroinvertebrate species
      collected from a single field site. Crustaceans were represented by two amphipod
      species, an epigean one (Gammarus fossarum) and a hypogean one (Niphargus
      rhenorhodanensis), and by an isopod species (Asellus aquaticus). There were two
      insect larvae, Heptagenia sulphurea (Ephemeroptera) and Hydropsiche pellucidula
      (Trichoptera) and a snail, Physa fontinalis. Median lethal concentrations (LC50s)
      were determined over 96-h and 240-h periods for chromium and over a 240-h period
      for arsenic. Arsenic bioaccumulation was studied, too. The macroinvertebrates
      tested showed a wide range of sensitivity and bioaccumulation. A comparison
      between 96-h and 240-h experiments demonstrated that there was an increase in
      toxicity values following a longer time exposure for chromium. Also chromium was
      more toxic toward crustaceans than arsenic; conversely, arsenic was more toxic
      for the insect larvae and snail tested here. The lethal concentrations determined
      for the two metals were discussed and compared to results from other toxicity
      studies. The use of such macroinvertebrates, collected in the field and tested
      for longer exposure periods than within the standardized 96-h tests, should
      provide more suitable results for monitoring the general environmental quality of
      freshwater systems.

PMID- 11443366
TI  - Organochlorine pesticides and PCBs in a southern Atlantic coastal lagoon
      watershed, Argentina.
AB  - There recently have been increasing interest in South America on organic
      pollutants from the coastal marine environment. This study intended to seek out
      the occurrence and distribution of persistent organochlorine compounds in the Mar
      Chiquita coastal lagoon watershed. The levels were measured in sediments and
      associated crabs. Though a significant number of PCBs (mainly penta- and
      hexachlorinated congeners) were detected, the concentrations were very low (in
      the order of ppbs), indicative of an estuarine environment with little industrial
      development. On the other hand, pesticide residues were higher than PCBs in one
      or two orders of magnitude, as a result of the important agricultural activities
      in the area. Heptachlor epoxide, DDT and its metabolites, and gamma-HCH were the
      predominant OC pesticides in sediments as well as in crabs. Significant
      differences among geographical areas: Channel 5 and Vivorata Creek (northern and
      southern sampling sites, respectively) contained detectable pesticide
      concentrations (heptachlor epoxide, DDE, DDD, and mirex).

PMID- 11443367
TI  - Use of Japanese medaka (Oryzias latipes) and Tilapia (Oreochromis mossambicus) in
      toxicity tests on different industrial effluents in Taiwan.
AB  - In Taiwan, aquatic toxicity tests for industrial effluents are not required for
      discharge permits. However, relying on traditional chemical and physical
      characteristics of an effluent to monitor and regulate such discharges to manage
      water quality of a receiving water is insufficient. In this study, we used two
      fish species, Japanese medaka (Oryzias latipes) and tilapia (Oreochromis
      mossambicus), and three toxic endpoints, including acute and subacute toxicity,
      to determine toxicity of seven different types of industrial effluents. Prior to
      the study, two reference toxicants were tested on two fish species. The LC50s of
      CdCl2 for tilapia and medaka juveniles were 29.6 +/- 15.3 mg/L and 2.2 +/- 1.2
      mg/L, respectively. The sensitivity of medaka embryo mortality and hatching
      inhibition to CdCl2 were about the same, with the LC50 and EC50 of 0.3 +/- 0.1
      mg/L and 0.1 +/- 0.1 mg/L, respectively. The LC50s for tilapia and medaka
      juveniles to sodium dodecyl sulfate (SDS) were 19.7 +/- 10.6 mg/L and 12.5 +/-
      5.9 mg/L. The medaka embryo was less sensitive to SDS than to CdCl2. The embryo's
      LC50 for SDS was 5.8 +/- 2.8 mg/L and the hatching inhibition EC50 was 1.3 +/-
      1.1 mg/L. Results of toxicity tests on different effluents showed that the
      electroplating effluent was the most toxic, followed by acrylonitrile
      manufacturing and pulp/paper mill discharges. The LC50s of the electroplating
      effluent to different assays were in the range of several percents of the whole
      effluent. The pulp/paper effluent was toxic only to the medaka embryo. The rest
      of the industrial effluents tested showed either moderate or no toxicity to the
      animals.

PMID- 11443368
TI  - Effects of dissolved copper on select hematological, biochemical, and
      immunological parameters of wild rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) were sampled from a creek in the western
      Sierra Nevada, Plumas County, CA, that receives run-off from a 40-ha copper (Cu)
      tailings pile. Reference sites included a site upstream of the Cu input and
      another site located on a nearby creek. Hepatic Cu concentrations were
      significantly elevated in trout from sites with elevated dissolved Cu
      concentrations compared with concentrations in trout from reference sites. Trout
      at the Cu-contaminated sites also exhibited decreased hematocrit (Hct), leukocrit
      (Lct), and percentage of lymphocytes in blood compared to trout from reference
      sites. The percentage of monocytes in blood and respiratory burst activity were
      affected by gender and age, respectively. Condition factor, percentage of
      neutrophils in blood, muscle glycogen and protein, and plasma
      acetylcholinesterase were not affected by dissolved Cu concentration or gender.
      Age also did not appear to be a factor. The data from this study support the use
      of immune system parameters to assess alterations in salmonids experiencing
      prolonged exposure to low-level Cu contamination and illustrate the variability
      in physiological responses of wild fish caused by demographic features. Overall,
      of the parameters measured, Hct, Lct, and percentage of lymphocytes in blood
      appeared to offer robust measures for assessing effects of metals on wild fish
      and did not appear affected by select demographic features.

PMID- 11443369
TI  - Nonuniform accumulation of cadmium and copper in kidneys of wild brown trout
      (Salmo trutta) populations.
AB  - Cadmium and copper accumulated nonuniformly in the kidney of wild brown trout on
      a longitudinal gradient as follows: the concentration in head kidney < anterior
      portion of tail kidney < posterior portion(s) of tail kidney. Zinc accumulated
      uniformly along the length of the kidney. Cadmium and copper accumulation in
      brown trout kidneys was lowest in the head kidney, where hematopoietic tissue
      dominates, and greatest in posterior tail sections, where filtration tissues
      dominate. Sampling programs designed to monitor cadmium and copper accumulation
      in trout kidneys should utilize the entire kidney, including the head kidney, to
      create comparable data sets.

PMID- 11443370
TI  - The effects of tributyltin (TBT) and 3,3',4,4',5-pentachlorobiphenyl (PCB-126)
      mixtures on antibody responses and phagocyte oxidative burst activity in channel
      catfish, Ictalurus punctatus.
AB  - The organotin tributyltin (TBT) is an antifouling biocide used in marine paints
      and is a common pollutant in harbor estuaries. We previously demonstrated that
      the immune system of channel catfish, Ictalurus punctatus, is a sensitive target
      organ of TBT. Exposure strongly suppresses humoral immune responses. Harbor
      estuaries often contain polychlorinated biphenyls (PCBs) due to their ubuquitous
      distribution. The coplanar congener 3,3',4,4'5'-polychlorinated biphenyl (PCB
      126) is also immunotoxic to channel catfish, but it suppresses only the innate
      immune responses and only at high doses. In this study we exposed channel catfish
      to TBT, PCB-126, or both in mixtures, with canola oil (CO) serving as the carrier
      control. Antibody responses to Vibrio anguillarum and phagocyte oxidative burst
      activity were measured after (1) a single dose of 0.01 or 1 mg/kg of each or both
      in combination, and (2) six injections of 1.7 or 170 microg/kg of each (or in
      combination) given every 3 days over a 16-day period to yield a cumulative dose
      of 0.01 or 1 mg/kg, respectively. We measured antibody responses to V.
      anguillarum 21 days after immunization and oxidative burst activities 14 and 21
      days after the final treatment. The highest dose of TBT suppressed antibody
      responses after a single exposure. The high dose of PCB-126 also suppressed
      antibody responses. The addition of PCB-126 to TBT doses did not alter the
      antibody responses beyond the effects of TBT alone. In the repeated exposure
      group, only the high dose of TBT suppressed antibody responses. In animals
      exposed to mixtures, high levels of PCB-126 enhanced suppression associated with
      low levels of TBT, whereas PCB-126 protected against suppression associated with
      high levels of TBT. Single exposures to TBT or PCB-126 suppressed phagocyte
      oxidative burst activity. In animals exposed to mixtures, as a single exposure,
      the addition of a low dose PCB-126 protected against low dose TBT-related
      oxidative burst activity suppression. In the repeated exposure groups TBT
      suppressed oxidative burst activity, but only at the highest dose on day 21,
      while high doses of PCB-126 suppressed activity on day 14. Furthermore, low
      levels of PCB-126 reversed the suppressed oxidative burst activity associated
      with high levels of TBT on day 21. Overall, this study demonstrates moderate
      additivity in terms of the immunotoxicity of TBT and PCB-126 mixtures using these
      two endpoints of immune function in the channel catfish model.

PMID- 11443371
TI  - Altered serum sex steroids and vitellogenin induction in walleye (Stizostedion
      vitreum) collected near a metropolitan sewage treatment plant.
AB  - Several recent in situ studies have reported that domestic and mixed
      domestic/industrial sewage effluents contain one or more natural or anthropogenic
      estrogenic substances. Those studies examined caged or feral fish for the
      presence of the egg yolk precursor protein, vitellogenin (VTG), in the blood of
      male fish. We have previously reported that male, feral carp (Cyprinus carpio)
      obtained from the effluent channel of a major sewage treatment plant (STP)
      exhibited depressed serum testosterone (T) concentrations, as well as detectable
      levels of VTG. The present study examines male and female walleye (Stizostedion
      vitreum), a native species with a different life history and feeding habits,
      collected from the same Mississippi River locations below the St. Paul
      metropolitan STP. All male and female walleye collected from the effluent channel
      contained measurable levels of VTG in their blood. Males from that location also
      exhibited depressed serum T concentrations and elevated serum estradiol-17beta
      (E2) concentrations compared with males from the Snake River reference site.
      Males obtained from Mississippi River Navigational Pool #2 (MRP-2), 3-20 miles
      downstream of the STP also exhibited reduced serum T concentrations, but showed
      no alterations in E2 concentrations or the presence of VTG in the serum. Females
      collected at the STP site had greatly elevated serum E2 concentrations, but serum
      T concentrations were not different from females collected in the Snake River.
      Our results demonstrate that the St. Paul metropolitan STP continues to release
      an estrogenic effluent, capable of inducing VTG production and altering normal
      serum sex steroid concentrations in a commercially valuable, native fish, the
      walleye. Additional studies will be required to determine whether these
      observations portend long-term population level effects.

PMID- 11443372
TI  - Failed recruitment of southern toads (Bufo terrestris) in a trace element
      contaminated breeding habitat: direct and indirect effects that may lead to a
      local population sink.
AB  - We conducted a transplant study in which embryonic southern toads (Bufo
      terrestris) were held in a site polluted with coal ash (site AB; containing As,
      Cd, Cr, Cu, Se, and other elements) and a reference site (site R) through
      hatching and early larval development. To examine the remainder of the larval
      period, surviving larvae in AB were then transplanted to R and back-transplanted
      to AB, whereas surviving larvae from R were back-transplanted to R. Survival
      through early larval development was lower in AB than in R (34% versus 50%).
      However, site of hatching did not influence traits later in development (larval
      metabolic rate, larval morphology, duration of larval period, size at
      metamorphosis, or average hopping distance by metamorphs). Toads that spent the
      entire larval period in R had high rates of survival (70-94% of individuals
      transplanted after the embryonic period) regardless of where they spent the
      embryonic and early larval period. However, toads held in AB for the duration of
      the larval period suffered 100% mortality. Algal resources were scarce and their
      trace element concentrations high in AB compared to R, suggesting that mortality
      of larval toads resulted from a combination of direct toxicity (via sediment- and
      foodborne exposure) and indirect effects on resource abundance. The study
      suggests that the widespread practice of disposing of coal ash in open aquatic
      basins may result in sink habitats for some amphibian populations.

PMID- 11443373
TI  - Sensitivity to urea fertilization in three amphibian species.
AB  - Forest fertilization with granular urea is a well-established management practice
      in many forested regions of the world. We hypothesize that chemical forest
      fertilizers may be affecting forest-dwelling wildlife. In the laboratory, we
      studied the effects of fertilization doses of granular urea on three species of
      forest-dwelling amphibians (Plethodon vehiculum, Rhyacotriton variegatus, and
      Taricha granulosa). In avoidance experiments, the three species avoided a
      substrate treated with a dose of 225 kg N/ha urea. In toxicity experiments, we
      exposed amphibians to urea at doses of 225 kg N/ha and 450 kg N/ha for 4 days.
      The observed effects increased with time and dose, and there were significant
      differences in sensitivity among the species. Both treatment levels had an acute
      effect on survival of P. vehiculum and R. variegatus. At 24 h, mortality at the
      highest dose was 67% for P. vehiculum, and 47% for R. variegatus. In contrast,
      there was no mortality for T. granulosa at these concentrations. We suggest that
      environmental levels of urea could be affecting behavior and survival of some
      amphibians species in fertilized forests.

PMID- 11443374
TI  - Organochlorine pesticides, PCBs, dibenzodioxin, and furan concentrations in
      common snapping turtle eggs (Chelydra serpentina serpentina) in Akwesasne, Mohawk
      Territory, Ontario, Canada.
AB  - Subsamples of eight clutches of common snapping turtle eggs (Chelydra serpentina
      serpentina) were collected from four sites from the territory of the Mohawk
      Nation, Akwesasne, on the shore of the St. Lawrence River. Egg contents were
      analyzed for organochlorine pesticides, polychlorinated biphenyls (PCBs),
      dibenzodioxins, and furans. The sites were 2 to 13 km downstream from PCB
      contaminated landfill sites. Maximum concentrations of total PCBs in snapping
      turtle clutches were extremely high, and ranged from 2 378.2 ng/g to 737 683 ng/g
      (wet weight) and are among the highest recorded in any tissue of a free-ranging
      animal. Similarly, in a pooled sample of eggs from all four sites, the summed
      concentrations of non-ortho PCBs (n = 6 congeners) was also very high at 54.54
      ng/g and the summed dioxin and furan concentrations (n = 11 congeners) was 85.8
      ng/g. Sum organochlorine pesticide levels varied from 28 to 2,264 ng/g among the
      four sites. The levels of PCBs found in turtle eggs exceed concentrations
      associated with developmental problems and reduced hatching success in snapping
      turtles and other species and also exceed the Canadian tissue residue guidelines
      for toxic equivalency concentrations. The extremely high levels of organochlorine
      contaminants demonstrate the high degree of contamination in the environment in
      the Akwesasne area.

PMID- 11443375
TI  - Effects of multiple exposures of small doses of Pembina Cardium crude oil and
      diesel in rats.
AB  - In lands used for agricultural purposes, petroleum- or diesel-contaminated wastes
      and accidental spills of crude oil at some drilling sites pose exposure risks for
      occupational public, livestock, and wildlife. This study has assessed the effects
      of an Alberta crude oil, Pembina Cardium crude oil (PCCO), and a commercial
      diesel fuel #2 (CDF-2) in Sprague-Dawley rats after repeated exposures at small
      dose levels. Rats were given by gavage on day 1, 3, 5, and 8 specified dosages of
      either the control vehicle, methylcellulose (MC) (1.25 ml/kg), or PCCO (0.25-1.25
      ml/kg), or CDF-2 (1.25 ml/kg). Exposure of rats to these dose levels of the test
      substances caused no overt symptoms of intoxication. A small but statistically
      significant increase in liver somatic index was observed in rats exposed to 1.25
      ml/kg doses of PCCO and CDF-2; however, kidney somatic index was not
      significantly affected by these treatments. Blood analyses for hematological and
      clinical indicators of systemic impairments did not show any significant changes
      (p > 0.05) between the control and PCCO- or CDF-2-exposed rats. Biochemical
      assessment of liver and kidney tissues showed that compared to the control group,
      the PCCO- and CDF-2-exposed groups had a marked and significant increase (p <
      0.05) in the hepatic activity of ethoxyresorufin-O-deethylase (EROD, a cytochrome
      P-450 [CYP] 1A1/A2-linked enzyme). In PCCO-exposed rats, the induction of EROD
      was dose-dependent. Exposure of rats with PCCO and CDF-2 also caused dose-related
      increases from the unexposed (control) or MC dosed rats in (1) hepatic activities
      of aryl hydrocarbon hydroxylase (AHH, a CYP 1A1-linked enzyme), ethoxycoumarin-O
      deethylase (ECOD, a CYP 2B/1A-linked enzyme), glutathione transferase (GT), and
      NADPH-catalyzed microsomal lipid peroxidation; and (ii) ECOD activity in kidneys.
      The induction of hepatic CYP-linked enzymatic activities by PCCO and CDF-2 could
      be due to de novo synthesis of selected isoforms, as evidenced by the relative
      differences in the inhibition of EROD activity with 7,8-benzoflavone or
      metyrapone.

PMID- 11443376
TI  - Cadmium in organic and conventional pig production.
AB  - The main sources of cadmium (Cd) input to soils have been phosphate fertilizers
      and deposition from air. In organic farming, phosphate fertilizers are not used,
      which may in the long term result in lower Cd levels. In the present study, feed,
      kidney, liver, and manure from growing/finishing pigs raised conventionally and
      organically on the same farm were microwave-digested and analyzed for Cd by
      graphite furnace atomic absorption spectrometry. Cd was also analyzed in soil and
      water. A quality control program was included. The organic pigs (n = 40) were
      raised outdoors and fed an organic feed; the conventional pigs (n = 40) were
      raised indoors and given a conventional feed. The Cd levels in organic and
      conventional feed were 39.9 microg/kg and 51.8 microg/kg, respectively. Organic
      feed contained 2% potato protein, which contributed 17% of the Cd content.
      Conventional feed contained 5% beet fiber, which contributed 38% of total Cd
      content. Both feeds contained vitamin-mineral mixtures with high levels of Cd:
      991 microg/kg in organic and 589 microg/kg in conventional feed. There was a
      significant negative linear relationship between Cd concentration in kidney and
      kidney weight. There was no significant difference in liver Cd levels between
      organic and conventional pigs and the mean +/- SD was 15.4 +/- 3.0. In spite of
      the lower level of Cd in the organic feed, the organic pigs had significantly
      higher levels in kidneys than the conventional pigs, 96.1 +/- 19.5 microg/kg wet
      weight (mean +/- SD; n = 37) and 84.0 +/- 17.6 microg/kg wet weight (n = 40),
      respectively. Organic pigs had higher Cd levels in manure, indicating a higher Cd
      exposure from the environment, such as ingestion of soil. Differences in feed
      compositions and bioavailability of Cd from the feed components may also explain
      the different kidney levels of Cd.

PMID- 11443377
TI  - Organochlorine pesticide levels in maternal adipose tissue, maternal blood serum,
      umbilical blood serum, and milk from inhabitants of Veracruz, Mexico.
AB  - Organochlorine pesticides, due to their persistence, accumulate in food chains
      and cause elevated contamination in human beings. These residues bioconcentrate
      in lipid-rich tissues according to the equilibrium pattern of internal transport
      and lipid tissue content. The analyses of maternal adipose tissue, maternal blood
      serum, umbilical blood serum, colostrum, and mature milk indicate circulation of
      these compounds through all compartments of the maternal body, including their
      crossover of the placental barrier. The greatest residue levels found correspond
      to DDTs, with highest levels determined in colostrum (5.71 mg/kg of DDT total),
      followed by adipose tissue with 5.66 mg/kg and in mature milk with 4.70 mg/kg.
      Among DDTs, pp'DDE is the most predominant compound. The paired analyses of
      organochlorine pesticide residue levels between mother blood serum and umbilical
      blood serum demonstrate significant correlation and their transfer from mother to
      fetus through the placenta. The paired analyses of adipose tissue and colostrum
      and mature milk contamination levels indicate a high degree of coherence,
      principally of DDT, in the body and lactation as a decontamination means.

PMID- 11443378
TI  - Hair mercury speciation as a function of gender, age, and body mass index in
      inhabitants of the Negro River basin, Amazon, Brazil.
AB  - Human mercury contamination can be monitored through hair analysis of mercury's
      inorganic and organic form as methylmercury (Me-Hg). Hair total mercury and Me-Hg
      were studied in a Negro River fish-eating population in relation to age, gender,
      and body mass index (BMI). This riverbank population eats fish at least twice a
      day and is exposed to high levels of Me-Hg. Total mercury ranged from 1.51
      microg/g to 59.01 microg/g, with only 21% of the sampled population having Hg
      concentration of less than 10 microg/g hair. The mean percentage of Me-Hg was
      71.3% (range 34% to 100%) of the total mercury in hair. No statistically
      significant differences were found in regard to age groups (children and adults)
      or BMI. However, women had significantly lower total mercury in hair than men,
      but the percentage of Me-Hg was not significantly different. Women in fertile age
      (15-40 years) had hair total mercury ranging from 1.65-32.63 microg/g, and 65% in
      this subgroup had hair mercury above 10 microg/g hair. The percentage of Me-Hg
      concentration in hair of this freshwater, fish-eating population is comparable to
      populations eating ocean fish from different parts of the world and does not seem
      to be affected by age, gender, and BMI.

PMID- 11443379
TI  - Adaptive management on public lands in the United States: commitment or rhetoric?
AB  - Adaptive management (AM) is the process of implementing land management
      activities in incremental steps and evaluating whether desired outcomes are being
      achieved at each step. If conditions deviate substantially from predictions,
      management activities are adjusted to achieve the desired outcomes. Thus, AM is a
      kind of monitoring, an activity that land management agencies have done poorly
      for the most part, at least with respect to ground-based monitoring. Will they do
      better in the future? We doubt it unless costs, personnel, and future commitment
      are seriously addressed. Because ecosystem responses to management impacts can
      ripple into the distant future, monitoring programs that address only the near
      future (e.g., 10-20 years), are probably unreliable for making statements about
      resource conditions in the distant future. We give examples of this. Feedback
      loops between ecosystem response and adjustment of management actions are often
      broken, and therefore AM again fails. Successful ground-based monitoring must
      address these and other points that agencies commonly ignore. As part of the
      solution, publics distrustful of agency activities should be included in any
      monitoring program.

PMID- 11443380
TI  - Industrial development versus environmental conservation at local scale: a case
      study from southeastern Spain.
AB  - Local scale has an important role in environmental management. In Spain, rapid
      industrialization has occurred in the last three decades, leading to substantial
      changes in socioeconomic relations and resulting in significant environmental
      degradation. This paper describes the environmental status of the township of Sax
      (Alicante, in southeast Spain), which has passed from agriculture to industrial
      manufacturing in 50 years. The human population has grown exponentially during
      the second half of the 20th century, with a 91% increase from 1955 to 1995,
      coinciding with strong growth in manufacturing (factories increased fivefold in
      the period 1955-1976) and important changes in the working population and land
      use. Illegal rubbish dumps, water pollution, forest fires, erosion, and
      degradation of wildlife habitats are the main outcomes of these dramatic
      socioeconomic and demographic changes. The administration has focused on the
      control of water pollution and waste management, while nongovernmental
      organizations have concentrated on the prevention of forest fires and the
      development of environmental education programs. These measures are insufficient
      to manage current environmental degradation, and an environmental management plan
      for the study area is discussed. Increasing effort in waste management and
      industrial wastewater control, changes in land-use policy, and the creation of an
      advisory committee to increase public participation in decision-making have been
      identified as environmental target objectives for the coming years.

PMID- 11443381
TI  - Does community-based conservation shape favorable attitudes among locals? an
      empirical study from nepal.
AB  - Like many developing countries, Nepal has adopted a community-based conservation
      (CBC) approach in recent years to manage its protected areas mainly in response
      to poor park-people relations. Among other things, under this approach the
      government has created new "people-oriented" conservation areas, formed and
      devolved legal authority to grassroots-level institutions to manage local
      resources, fostered infrastructure development, promoted tourism, and provided
      income-generating trainings to local people. Of interest to policy-makers and
      resource managers in Nepal and worldwide is whether this approach to conservation
      leads to improved attitudes on the part of local people. It is also important to
      know if personal costs and benefits associated with various intervention
      programs, and socioeconomic and demographic characteristics influence these
      attitudes. We explore these questions by looking at the experiences in Annapurna
      and Makalu-Barun Conservation Areas, Nepal, which have largely adopted a CBC
      approach in policy formulation, planning, and management. The research was
      conducted during 1996 and 1997; the data collection methods included random
      household questionnaire surveys, informal interviews, and review of official
      records and published literature. The results indicated that the majority of
      local people held favorable attitudes toward these conservation areas. Logistic
      regression results revealed that participation in training, benefit from tourism,
      wildlife depredation issue, ethnicity, gender, and education level were the
      significant predictors of local attitudes in one or the other conservation area.
      We conclude that the CBC approach has potential to shape favorable local
      attitudes and that these attitudes will be mediated by some personal attributes.

PMID- 11443382
TI  - Assessing public participation techniques for comfort, convenience, satisfaction,
      and deliberation.
AB  - Public participatory techniques have been the focus of a large and growing body
      of environmental literature. There is some consensus among those who study these
      techniques that there is a need to develop and implement new techniques that meet
      certain criteria. These include that the techniques be comfortable, convenient,
      and satisfying to participants. Authors have also frequently called for the use
      of deliberative techniques, which allow participants to express and listen to a
      variety of perspectives regarding the issue at hand. However, the literature on
      public participation lacks a set of widely applicable evaluation methods to
      determine whether participants in techniques find them comfortable, convenient,
      satisfying, or deliberative. This paper reports on the implementation of two
      different techniques that participants scored fairly high on all of these
      factors, as well as the scale-based survey questions developed to measure these
      factors.

PMID- 11443383
TI  - Environmental initiative prioritization with a Delphi approach: a case study.
AB  - India is fast finding its place in the industrialized world and that is beginning
      to raise its environmental consciousness. The Delphi technique was used to
      prioritize specific needs and articulate a sustainable urban improvement strategy
      for the city of Mumbai (formerly Bombay). The Delphi technique is a means of
      achieving consensual validity among raters by providing them feedback regarding
      other raters' responses. Mumbai has several indigenous environmental groups that
      were tapped for activists and leaders; the study was conducted using ten
      environmentalists. In the initial phases the responses resulted in a range of
      possible program alternatives. The last two stages helped to seek out information
      that generated a consensus on the part of the respondent group. Statistical
      analysis methods included a hierarchical cluster analysis, mean, median, mode,
      and percent of agreement calculations using SPSS software. The face-to-face
      discussion in phase 4 clarified some issues and helped the group as a whole to
      outline the strategy for putting in place the essential elements of a framework
      to improve the quality of life in an urban environment.

PMID- 11443384
TI  - Nest-Site Selection by black sparrowhawks Accipiter melanoleucus: implications
      for managing exotic pulpwood and sawlog forests in South Africa.
AB  - This study provides timber growers with silvicultural guidelines for establishing
      and maintaining nest-tree habitat for native black sparrowhawks (Accipiter
      melanoleucus) in commercial planted forests in South Africa. In this country,
      exotic eucalypts and pines are planted principally for pulpwood and sawlog
      production. Nineteen nests were sampled in indigenous forests and 58 nests in
      exotic forests. Although mean nest heights differed between indigenous and exotic
      trees, in all trees, nests were positioned, on average, at 64% of tree height.
      Black sparrowhawks nested near stand edges, probably seeking a compromise between
      nesting adjacent to open hunting habitat and selecting an insulated tree from
      within the forest. Black sparrowhawks nested in tall trees ( X- = 18-33 m for
      different tree species classes) with a large diameter (>60 cm). Unfortunately,
      the South African pulpwood and sawlog industry employ short rotations (<16 years)
      and high tree densities (>700 trees/ha) that do not allow the trees to attain the
      characteristics suitable for black sparrowhawk nesting sites. Eucalypt and pine
      nest stands must be of 25 x 25 m minimum size and incorporate 10 trees at minimum
      heights of 21 and 18 m and diameters of 37 and 35 cm, respectively. If such nest
      tree stands are set aside as islands in a sea of commercial forests, and black
      sparrowhawks and other forest raptors nest in them, timber growers will improve
      the tree-nesting raptor diversity of planted forests. If, however, these raptors
      prey upon species of conservation importance, the management recommendations
      could be reversed to limit the potential for predation.

PMID- 11443385
TI  - Managing birds and controlling aircraft in the kennedy airport-jamaica bay
      wildlife refuge complex: the need for hard data and soft opinions.
AB  - During the 1980s, the exponential growth of laughing gull (Larus atricilla)
      colonies, from 15 to about 7600 nests in 1990, in the Jamaica Bay Wildlife Refuge
      and a correlated increase in the bird-strike rate at nearby John F. Kennedy
      International Airport (New York City) led to a controversy between wildlife and
      airport managers over the elimination of the colonies. In this paper, we review
      data to evaluate if: (1) the colonies have increased the level of risk to the
      flying public; (2) on-colony population control would reduce the presence of
      gulls, and subsequently bird strikes, at the airport; and (3) all on-airport
      management alternatives have been adequately implemented. Since 1979, most (2987,
      87%) of the 3444 bird strikes (number of aircraft struck) were actually bird
      carcasses found near runways (cause of death unknown but assumed to be bird
      strikes by definition). Of the 457 pilot-reported strikes (mean = 23 +/- 6
      aircraft/yr, N = 20 years), 78 (17%) involved laughing gulls. Since a gull
      shooting program was initiated on airport property in 1991, over 50,000 adult
      laughing gulls have been killed and the number of reported bird strikes involving
      laughing gulls has declined from 6.9 +/- 2.9 (1983-1990) to 2.6 +/- 1.3 (1991
      1998) aircraft/yr; nongull reported bird strikes, however, have more than doubled
      (6.4 +/- 2.6, 1983-1990; 14.9 +/- 5.1, 1991-1998). We found no evidence to
      indicate that on-colony management would yield a reduction of bird strikes at
      Kennedy Airport. Dietary and mark-recapture studies suggest that 60%-90% of the
      laughing gulls collected on-airport were either failed breeders and/or
      nonbreeding birds. We argue that the Jamaica Bay laughing gull colonies, the only
      ones in New York State, should not be managed at least until all on-airport
      management alternatives have been properly implemented and demonstrated to be
      ineffective at reducing bird strikes, including habitat alterations and
      increasing the capability of the bird control unit to eliminate bird flocks on
      airport using nonlethal bird dispersal techniques. Because the gull-shooting
      program may be resulting in a nonsustainable regional population of laughing
      gulls (>30% decline), we also recommend that attempts be made to initiate an
      experimental colony elsewhere on Long Island to determine if colony relocation is
      a feasible management option.

PMID- 11443386
TI  - Developing an ecosystem perspective from experimental monitoring programs: I.
      Demographic responses of a rare geothermal grass to soil temperature.
AB  - The geysers panic grass [Dichanthelium lanuginosum Spellenberg var. thermale
      (Bol.) Spellenberg or DILA] is exclusively associated with surface geothermal
      manifestations in Sonoma County, California, USA (38 degrees 46'N, 122 degrees
      38'W). Steam extraction by power plants could alter the subsurface distribution
      of heat and water to the site, potentially impacting subpopulations of this rare
      plant. The purpose of this study was to use demographic monitoring to determine:
      (1) temporal and spatial patterns of soil temperature in relation to the
      distribution of established DILA individuals at Little Geysers, (2) in situ
      response of experimental populations of DILA to spatial variations in soil
      temperature, and (3) habitat requirements of DILA as an indicator of its
      tolerance to variations in surficial geothermal features. Thermocouple transects
      and a datalogger provided data for characterizing the spatial and temporal
      patterns of soil temperature in four microhabitats (fumarole, DILA stand,
      Andropogon stand, and cleared). Experimental populations were established by
      precisely sowing and monitoring DILA seeds in these microhabitats. The results
      indicated that spatial and temporal variations in soil temperature had
      significant effects on the processes of germination, growth, survivorship, and
      reproduction, thus producing a readily observed metapopulation patch dynamic in
      relation to geothermal activity. Seasonal depressions of soil temperature near
      the fumaroles by cold air and prolonged rainfall events also promoted the
      emergence and survival of DILA seedlings in a microhabitat that was previously
      too hot to occupy. Over longer periods of time, DILA metapopulation dynamism
      reflected climatic and geothermal variation. Drought years inhibited germination
      for lack of water, but more importantly for the lack of requisite soil
      temperature depressions in the fumarole microhabitat. Wet years promoted
      subpopulation expansion into transition areas that were once too hot and dry.
      There have also been shifts in the underground distribution of steam into areas
      distant from known geothermal features. The demographic responses of DILA to
      spatial and temporal variations in soil temperature indicate that heat is an
      absolutely essential component of the steam resource. In its absence,
      germination, seeding survivorship, growth, and maturation are significantly
      inhibited even if soil conditions are favorable and potential competitors are
      controlled. Ultimately, persistence of the species depends on maintaining the
      ecosystem dynamic of colonization and extirpation in response to variations in
      surficial geothermal features over long spatial and temporal scales. This should
      shift management perspective from its narrow focus on individual plants to a
      wider focus on monitoring the essential habitat component of steam.

PMID- 11443387
TI  - Developing an ecosystem perspective from experimental monitoring programs: II.
      Ecophysiological responses of a rare geothermal grass to soil water.
AB  - Measurements of xylem water potential, leaf conductance, and leaf pressure-volume
      characteristics on the geothermal endemic Dichanthelium lanuginosum var. thermale
      (DILA) were used to delineate operational ranges during wet and dry years and
      among several microsites at Little Geysers, Sonoma County, California, USA.
      Plants seldom experienced water potentials more negative that -1.5 MPa. Other
      nongeothermal, widespread species experienced the lower water potentials typical
      of chaparral and woodland plants. DILA was able to effectively utilize geothermal
      water while the widespread species could not and was able to keep stomata open
      during most of the year. There was evidence to suggest that DILA had some ability
      to acclimate with significant shifts in Pio and psio during the dry 1994 summer,
      especially in the upland microhabitat. Nevertheless, minimum leaf turgor values
      in the upland came very close to, or dropped below, the 0.2-0.3 MPa threshold
      thought necessary to maintain stomatal opening and photosynthesis. DILA thus
      depends upon the unique water status of fumarole soils in the vicinity of the
      Little Geysers to persist in an otherwise lethal regional mosaic of climate,
      soil, and vegetation. The physiological data were used to derive reference ranges
      for subsequent monitoring of DILA at Little Geysers. Such ranges are required to
      determine the future impact, if any, of geothermal development on the persistence
      of this rare grass and its complex ecosystem.

PMID- 11443388
TI  - Impacts of urbanization on stream habitat and fish across multiple spatial
      scales.
AB  - We analyzed the relation of the amount and spatial pattern of land cover with
      stream fish communities, in-stream habitat, and baseflow in 47 small southeastern
      Wisconsin, USA, watersheds encompassing a gradient of predominantly agricultural
      to predominantly urban land uses. The amount of connected impervious surface in
      the watershed was the best measure of urbanization for predicting fish density,
      species richness, diversity, and index of biotic integrity (IBI) score; bank
      erosion; and base flow. However, connected imperviousness was not significantly
      correlated with overall habitat quality for fish. Nonlinear models were developed
      using quantile regression to predict the maximum possible number of fish species,
      IBI score, and base flow for a given level of imperviousness. At watershed
      connected imperviousness levels less than about 8%, all three variables could
      have high values, whereas at connected imperviousness levels greater than 12%
      their values were inevitably low. Connected imperviousness levels between 8 and
      12% represented a threshold region where minor changes in urbanization could
      result in major changes in stream condition. In a spatial analysis, connected
      imperviousness within a 50-m buffer along the stream or within a 1.6-km radius
      upstream of the sampling site had more influence on stream fish and base flow
      than did comparable amounts of imperviousness further away. Our results suggest
      that urban development that minimizes amount of connected impervious surface and
      establishes undeveloped buffer areas along streams should have less impact than
      conventional types of development.

PMID- 11443389
TI  - Strategic environmental assessment of plans and programs: a methodology for
      estimating effects on biodiversity.
AB  - We developed a methodology for biodiversity evaluations within the process of
      Strategic Environmental Assessment and we applied it to the estimation of the
      effect of two Regional Plans of Development on all bird species inhabiting the
      Castilla y Leon region (northwestern Spain). The methodology is based on the
      evaluation of the effects of main development actions on the habitat requirements
      of species. From these evaluations, and from data on the current distribution and
      population size (number of individuals) of each species, we estimated the most
      likely pattern of distribution and population size after the full implementation
      of the plans for each species. The impacts of the plans were quantified as the
      differences between the pre- and postproject patterns after codifying them to
      compensate for differences in the quality of the information available among
      species. Overall, we conclude that the proposed methodology fulfills the
      requirements for its use within the SEA process as it allows for the assessment
      of cumulative impacts on every species, highlighting the development directions
      and the habitat types with major impacts, and ascertaining whether impacts affect
      species with either low or high conservation and/or economic value.
      Generalization of the proposed methodology to other regions or species will
      require wildlife-habitat models adequate for SEA analyses, so that we also
      propose guidelines for the development and validation of these models.

PMID- 11443390
TI  - Femoropopliteal artery obstructions: from the balloon to the stent-graft.

PMID- 11443391
TI  - Intracardiac ultrasound assessment of atrial septal defect: comparison with
      transthoracic echocardiographic, angiocardiographic, and balloon-sizing
      measurements.
AB  - PURPOSE: Accurate evaluation of the size, location and adjacent structure of an
      atrial septal defect (ASD) is very important in the selection of patients for
      further management. We directly compared the utility of transthoracic
      echocardiography, angiocardiography, balloon sizing, and intracardiac ultrasound
      (ICUS) in the detection of ASD. METHODS: Twenty-one children underwent an ICUS
      study of ASD after routine clinical and laboratory studies. All patients had
      received transthoracic echocardiography (TTE), cardiac catheterization,
      cineangiography, and balloon sizing before the ICUS to evaluate the ASD. RESULTS:
      There was a significant correlation between the ICUS-derived ASD diameter and the
      other methods (p < 0.001). The balloon-sizing diameter was estimated by the
      equation: TTE diameter x 1.09 + 3.9 mm. There was a good correlation between the
      predicted and measured balloon-sizing diameter (r = 0.963; p < 0.001).
      CONCLUSION: It is worthwhile spending a few minutes to perform ICUS during
      cardiac catheterization since it will provide more detailed information on and
      high resolution images of atrial septal morphology, especially for patients
      undergoing transcatheter closure by device.

PMID- 11443392
TI  - Complications encountered with a transfemorally placed port-catheter system for
      hepatic artery chemotherapy infusion.
AB  - A port-catheter system was implanted via femoral artery access for hepatic artery
      chemotherapy infusion. Implantation was attempted in 90 patients and was
      successful in 88. Blood flow redistribution was performed using embolization
      coils. In the first ten patients a soft heparin-coated infusion catheter was
      used. For the following 78 patients we used a stiffer catheter coated with
      fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer. The catheter was
      connected to a port implanted subcutaneously below the level of the inguinal
      ligament. Complications during the procedure and after placement were observed in
      7 of 90 patients and 24 of 88 patients, respectively. These included catheter
      obstruction (11%), dislocation of the catheter tip (10%), drug toxicity (5.7%),
      and catheter infection (3.4%). In 6 of 10 patients with catheter obstruction,
      recanalization of the port system was achieved. In 7 of 9 patients with
      dislocation of the indwelling catheter tip, replacement of the port system was
      successful. Our complications appear to be comparable with those encountered with
      the subclavian/brachial approach when the new catheter coating is used. Notable
      is the avoidance of cerebral infarcts.

PMID- 11443393
TI  - Dilatation of stent-grafts by luminal pressures: experimental evaluation of
      polytetrafluoroethylene (PTFE) and woven polyester grafts.
AB  - PURPOSE: To evaluate the effect on dilatation of three types of covering
      materials used for endovascular stent-grafts. METHODS: Stent-grafts with three
      types of covering material [0.1-mm polytetrafluoroethylene (PTFE), 0.2-mm PTFE,
      and 0.15-mm woven polyester] were placed in a fluid circuit. For the pulsatile
      pressure test, the luminal pressure of 190/130 mmHg was loaded up to 300,000
      pulses. For the static pressure test, the luminal pressure was increased from 50
      to 300 mmHg at 50-mmHg increments. The percent of dilatation of each stent-graft
      was compared. RESULTS: The 0.1-mm PTFE stent-graft was significantly more dilated
      than the 0.2-mm PTFE and the 0.15-mm woven polyester stent-graft (p < 0.005) in
      both examinations. There was no significant difference between the 0.2-mm PTFE
      and the 0.15-mm woven polyester stent-grafts. The dilatation of the 0.1-mm PTFE
      stent-graft was irreversible. CONCLUSION: The 0.15-mm woven polyester and the 0.2
      mm PTFE stent-grafts may be preferable to the 0.1-mm PTFE stent-graft with regard
      to dilatation and deformity.

PMID- 11443394
TI  - Endoluminal treatment of ruptured abdominal aortic aneurysm with small intestinal
      submucosa sandwich endografts: a pilot study in sheep.
AB  - PURPOSE: To evaluate efficacy of small intestinal submucosa (SIS) Sandwich
      endografts for the treatment of acute rupture of abdominal aortic aneurysms (AAA)
      and to explore the short-term reaction of the aorta to this material. METHODS: In
      eight adult sheep, an infrarenal AAA was created transluminally by dilation of a
      short Palmaz stent. In six sheep, the aneurysm was then ruptured by overdilation
      of the stent with a large angioplasty balloon. Two sheep with AAAs that were not
      ruptured served as controls. A SIS Sandwich endograft, consisting of a Z stent
      frame with 5 bodies and covered inside and out with SIS, was used to exclude the
      ruptured and non-ruptured AAAs. Follow-up aortography was done immediately after
      the procedure and before sacrifice at 4, 8, or 12 weeks. Autopsy and histologic
      studies followed. RESULTS: Endograft placement was successful in all eight sheep.
      Both ruptured and non-ruptured AAAs were successfully excluded. Three animals
      with AAA rupture developed hind leg paralysis due to compromise of the arterial
      supply to the lower spinal cord and were sacrificed 1 day after the procedure. In
      five animals, three with rupture and two controls, follow-up aortograms revealed
      no aortic stenoses and no perigraft leaks. Gross and histologic studies revealed
      incorporation of the endografts into the aortic wall with replacement of SIS by
      dense neointima that was completely endothelialized in areas where the endograft
      was in direct contact with the aortic wall. In central portions of the endograft,
      in contact with the thrombosed aneurysm, endothelialization was incomplete even
      at 12 weeks. CONCLUSION: The SIS Sandwich endografts effectively excluded simple
      AAAs and ruptured AAAs. They were rapidly incorporated into the aortic wall. A
      detailed long-term study is warranted.

PMID- 11443395
TI  - CT-guided transfemoral portocaval shunt creation.
AB  - A patient with superior vena cava (SVC) occlusion presented with severe ascites
      and urgent transjugular intrahepatic portosystemic shunt (TIPS) was requested.
      The patient had a chronically occluded SVC. An alternative to classic TIPS was
      employed using CT guidance to traverse the left portal vein to the inferior vena
      cava with a small gauge needle. Fluoroscopic guidance was then used to snare a
      wire placed through the needle and then work from the femoral vein to create a
      portocaval shunt that passed through the caudate lobe. This procedure was a
      technical success and improved the patient's ascites.

PMID- 11443396
TI  - Endoluminal repair of a Dardik prosthesis pseudoaneurysm using the wallgraft
      endoprosthesis.
AB  - A 58-year-old man with a history of severe invalidating claudicatio intermittens
      underwent femoropopliteal bypass with a human umbilical vein graft. Seven years
      later he presented with a painful enlarging mass in the middle portion of his
      right thigh. The duplex scan showed a pseudoaneurysm of the body of the
      prosthesis, which was confirmed by angiography. As an alternative to surgical
      management, Wallgraft endoprosthesis was used for endoluminal exclusion of the
      pseudoaneurysm. To our knowledge, this technique has never been used before in
      such a case.

PMID- 11443397
TI  - Iliac artery injury following placement of the memotherm arterial stent.
AB  - Iliac rupture and aneurysm formation at the site of stent placement has rarely
      been described in the literature. We report four cases, three of iliac rupture,
      including a delayed rupture, and an aneurysm, with the use of a single type of
      stent, the Memotherm stent. We believe the design of the stent significantly
      contributed to damage to the arterial wall and subsequently prevented closure of
      the arterial tear by balloon tamponade in the two cases where this was attempted.
      Two patients, one with rupture and one with an aneurysm, were successfully
      treated with a covered stent obviating surgery and two ruptures resulted in
      death. We recommend that all interventionists carrying out iliac angioplasty
      and/or stenting should have access to covered stents for such emergencies.

PMID- 11443398
TI  - The spectrum of findings in supra-aortic Takayasu's arteritis as seen on spiral
      CT angiography and digital subtraction angiography.

PMID- 11443399
TI  - Closure using a surgical closure device of inadvertent subclavian artery
      punctures during central venous catheter placement.
AB  - Severe complications can and do occur when central venous catheters are
      inadvertently placed into subclavian arteries. Two cases are discussed that
      describe how these inadvertent arterial punctures can be closed using the
      Perclose device (Abbott Laboratories, Redwood City, CA, USA).

PMID- 11443400
TI  - Re: Continuous hemorrhage from transdiaphragmatic empyema necessitatis due to
      tuberculosis: preoperative flow control by arterial embolization.

PMID- 11443401
TI  - Gastric and duodenal stents: follow-up and complications.
AB  - PURPOSE: To assess the efficacy of self-expanding metallic stents in treating
      inoperable gastric and duodenal stenoses during follow-up and to evaluate the
      complications encountered. METHODS: A total of 31 patients suffering from
      gastroduodenal obstruction (29 malignant, 2 benign) were treated with a self
      expanding metallic stent (Wallstent). In 24 cases insertion was by the peroral
      route, in seven cases via gastrostomy. RESULTS: All the strictures were
      successfully negotiated under fluoroscopic guidance without having to resort to
      endoscopy. A total of 27 patients (87%) were able to resume a regular diet, a
      soft diet, or a liquid diet orally. Complications included one case of stent
      malpositioning, one case of leakage of ascitic fluid through the gastrostomy
      orifice, one case of perforation and fistula to the biliary tree, and two cases
      of hematemesis. In two patients (6%) additional stents were implanted to improve
      patency. In all patients follow-up was maintained until death. Recurrence of
      symptoms immediately before death occurred in seven cases (23%). Mean survival
      time of patients was 13.3 weeks (SE +/- 4.6). CONCLUSIONS: The deployment of
      gastroduodenal stents resulted in good palliation of inoperable gastric and
      duodenal stenoses. Certain technical aspects, e.g., adaptation of stents to bowel
      morphology, is critical to proper stent function and avoidance of complications.

PMID- 11443402
TI  - Subintimal recanalization of long superficial femoral artery occlusions through
      the retrograde popliteal approach.
AB  - PURPOSE: To investigate the value of the retrograde popliteal artery approach for
      the percutaneous intentional extraluminal recanalization (PIER) of long
      superficial femoral artery (SFA) occlusions. METHODS: During a period of 17
      months, PIER through ultrasound-guided retrograde popliteal artery puncture was
      performed for 39 long SFA occlusions in 37 patients. In six patients, six
      additional iliac artery stenoses were also treated via the popliteal approach.
      RESULTS: The procedure was technically successful in 32 (82%) of 39 SFA
      occlusions; in 29, lesions were treated with balloon angioplasty alone, and in
      three, stents were also used. Cumulative patency rate was 66% at 6 months, 62% at
      1 year, and 59% at 18 months. Additional iliac artery stenoses were successfully
      treated in the same session. Complications included two minor hematomas and two
      SFA ruptures, which required no treatment. CONCLUSION: PIER through retrograde
      popliteal puncture is a safe and effective method in the treatment of long
      femoropopliteal occlusions, with a high technical success, low complication rate
      and a reasonable short-term patency rate. The technique offers an alternative in
      cases where standard PIER is unsuccessful or contraindicated.

PMID- 11443403
TI  - Frequency of arteriovenous shunts in hepatic cavernous hemangiomas in adults as
      seen on selective arteriography and postembolization radiography.
AB  - PURPOSE: To study the frequency and angiographic findings of arteriovenous shunts
      (AVS) associated with adult cavernous hemangiomas of the liver (CHL) on hepatic
      artery digital subtraction angiography (DSA) and optimize the imaging technique
      of DSA to improve its diagnostic efficacy. METHODS: We retrospectively analyzed
      43 intraarterial DSA procedures performed on 30 adults with CHL. Of the 30
      patients 22 were found to have an AVS. Transcatheter arterial embolization with
      Lipiodol (L-TAE) was performed on 21 of these and radiographs were taken
      immediately after embolization to observe the distribution of the injected
      iodized oil. The results were compared with those of the AVS found on DSA images.
      RESULTS: AVS were identified by DSA in 22 (73.3%) of 30 patients. All AVS were
      located in the peritumoral liver tissue and had a parallel track appearance, or
      early filling of small draining veins during the arterial phase of DSA.
      Radiographs taken immediately after L-TAE in 21 of the 22 cases with AVS showed
      iodized oil filling a few portal branches or draining veins as a result of
      incompletely occluded shunts in 11 patients. In 10 patients there was complete
      occlusion and no filling of any vein, or only the originating end of draining
      veins filled with iodized oil. No evidence of AVS was found in the other eight
      patients in this series, and in six of these the DSA was not considered
      diagnostic. CONCLUSION: The present study indicates that AVS are frequently seen
      in adults with CHL. DSA with high-quality images is helpful in identifying small
      AVS of CHL. The formation of an AVS in CHL may be closely related to the
      pathological changes in the peritumoral liver tissue.

PMID- 11443404
TI  - Popliteal artery stenting using flexible tantalum stents.
AB  - PURPOSE: To evaluate the safety and efficacy of stent therapy for the treatment
      of residual stenoses after percutaneous transluminal angioplasty (PTA) of
      popliteal stenoses and occlusions. METHODS: In a prospective single-center study,
      flexible tantalum stents were implanted in 32 popliteal arteries for the
      treatment of residual stenosis greater than 50% after PTA of stenoses (n = 17) or
      occlusions (n = 15) in the P1 (n = 16), the P2 (n = 13), or both P1 and P2
      segment (n = 3). Follow-up patency was assessed by clinical examination, ankle
      brachial index, and color Doppler sonography or angiography. RESULTS: Early stent
      thrombosis (10 days): 1 of 32 arteries (3%). 1-year and 2-year primary patency
      rate (PPR): 81% +/- 7.1% and 74% +/- 9.1%, respectively. 1-year PPRs for
      subgroups: stented stenoses versus stented occlusions: 88% +/- 7.8% vs 73% +/-
      12.0%, p = 0.12; good lower limb runoff versus poor: 84.0% +/- 8.7% vs 76.0% +/-
      12.4; p = 0.09; P1 versus P2: 77.3% +/- 9.8% vs 85.7% +/- 9.4%, p = 0.38.
      Recurrent PTA lesions treated with stents showed higher restenosis rate than de
      novo lesions. CONCLUSION: The results of stent therapy of residual popliteal
      stenosis after PTA are encouraging and warrant further investigation.

PMID- 11443405
TI  - Intraarterial chemotherapy or chemoembolization for locally advanced and/or
      recurrent hepatic tumors: evaluation of the feeding artery with an interventional
      CT system.
AB  - PURPOSE: To evaluate the utility of an interventional CT system for intraarterial
      chemotherapy or chemoembolization for locally advanced and/or recurrent hepatic
      tumors. METHODS: Thirty-eight patients with locally advanced or recurrent hepatic
      tumors underwent 73 intraarterial contrast-enhanced CT (IA-CECT) examinations
      immediately before chemotherapy or chemoembolization. The degree of tumor
      vascularity on angiography and enhancement on IA-CECT was classified into three
      grades: no, mild, or marked vascularity. The IA-CECT grades were compared with
      the angiographic grades. RESULTS: Twenty-nine (69%) of 42 examinations that were
      interpreted as having no or mild vascularity on angiography were classified as
      marked enhancement on IA-CECT. Based on IA-CECT findings, the position of the
      catheter was changed in 14 (19%) of 73 CT examinations. The reasons for the
      reposition were as follows: weak or no enhancement of the tumor (n = 11) or
      strong enhancement of the gallbladder wall (n = 3). The treatment strategy was
      changed in three patients (8%). No major complications relating to the
      interventional procedures were observed. CONCLUSIONS: IA-CECT is a reliable
      method when evaluating the perfusion of the tumor and adjacent normal tissues.
      The interventional CT system is useful for performing safe and effective
      intraarterial chemotherapy or chemoembolization in patients with locally advanced
      and/or recurrent hepatic tumors.

PMID- 11443406
TI  - Central venous access ports placed by interventional radiologists: experience
      with 125 consecutive patients.
AB  - PURPOSE: To assess safety and function of central venous port systems implanted
      percutaneously in the interventional radiology suite. METHODS: One hundred and
      twenty-five consecutive ports in 123 patients were evaluated retrospectively. One
      hundred and twenty ports were implanted via the subclavian vein. RESULTS:
      Technical success was 100%. Fourteen patients (11.2%) experienced immediate
      procedural complications, all minor (pneumothorax 1.6%). During follow-up (4-343
      days, mean service period 97.8 days), nine complications occurred, six of which
      were major. These were three port infections which led to hospitalization and
      port removal, one chamber penetration through the skin, and two port occlusions.
      Port removal as a result of complications was performed in six patients.
      Altogether, 20 complications occurred within a total of 11,056 days of service,
      which means 1.8 events per 1000 days of service. CONCLUSION: Percutaneous
      implantation of central venous port systems is safe and easy to perform.
      Complication rates of this study compare favorably with those of other
      radiological and surgical series.

PMID- 11443407
TI  - Safety of conscious sedation in interventional radiology.
AB  - PURPOSE: To identify rates of adverse events associated with the use of conscious
      sedation in interventional radiology. METHODS: In a 5-month period, prospective
      data were collected on patients undergoing conscious sedation for interventional
      radiology procedures (n = 594). Adverse events were categorized as respiratory,
      sedative, or major adverse events. Respiratory adverse events were those that
      required oral airway placement, ambu bag, or jaw thrust. Sedation adverse events
      were unresponsiveness, oxygen saturation less than 90%, use of
      flumazenil/naloxone, or agitation. Major adverse events were hypotension,
      intubation, CPR, or cardiac arrest. The frequency of adverse events for the five
      most common radiology procedures were determined. RESULTS: The five most common
      procedures (total n = 541) were biliary tube placement/exchange (n = 182),
      tunneled catheter placement (n = 135), diagnostic arteriography (n = 125),
      vascular interventions (n = 52), and other catheter insertions (n = 46). Rates
      for respiratory, sedation, and major adverse events were 4.7%, 4.2%, and 2.0%,
      respectively. The most frequent major adverse event was hypotension (2.0%).
      Biliary procedures had the highest rate of total adverse events (p < .05) and
      respiratory adverse events (p < .05). CONCLUSION: The frequency of adverse events
      is low with the use of conscious sedation during interventional procedures. The
      highest rates occurred during biliary interventions.

PMID- 11443408
TI  - Double-balloon catheter for isolated liver perfusion: an experimental study.
AB  - PURPOSE: Further development of a previously described interventional method for
      isolated liver perfusion (ILP) with a new double-lumen balloon catheter, and
      evaluation of the side-effects of such isolation. METHODS: In six pigs a double
      balloon occlusion catheter was placed via the transjugular approach with its tip
      in the portal vein. One of the balloons was positioned in the inferior vena cava
      (IVC), cranial to the origin of the hepatic veins and the other balloon in the
      portal vein. By the transfemoral approach, a single-balloon occlusion catheter
      was placed in the IVC caudal to the origin of the hepatic veins. A third catheter
      was placed by the transfemoral route with the occlusion balloon in the proper
      hepatic artery. After inflation of all balloons 99Tc(m)-labelled human serum
      albumin was recirculated through the liver. The isolation was evaluated by
      repeated measurement of radioactivity levels in peripheral blood. Laboratory
      tests of liver and pancreas function, and hemoglobin, were taken before, at the
      end of, and 3 days after the procedure. Blood gases were tested at the beginning
      and end of the procedure. RESULTS: One pig died during the procedure due to
      technical failure and was excluded from the study. In the other pigs leakage from
      the isolated liver to the systemic circulation increased slowly, up to 9.7%
      (mean) during 30 min of recirculation of the perfusate through the liver.
      Laboratory tests were normal in all pigs except insignificant acidosis directly
      after the procedure and the slight elevation of s-ALAT after 3 days. CONCLUSIONS:
      Only minor leakage from the liver to the systemic circulation was noted during
      ILP performed with a new, double-balloon catheter. There were no serious side
      effects.

PMID- 11443409
TI  - Treatment of occluded distal splenorenal shunts with endovascular stents: a
      report of two cases.
AB  - Surgical treatment of an occluded or stenotic portosystemic shunt is difficult
      and carries a high risk of mortality. We report two cases of early thrombosis of
      distal splenorenal shunt (DSRS) successfully treated by transcatheter
      recanalization and stent placement. At 18-month follow-up, the patients remained
      asymptomatic and control venograms showed continued patency of the shunt with no
      evidence of stenosis or collaterals.

PMID- 11443410
TI  - Carotid stenting in a case of combined kinking and stenosis.
AB  - Endarterectomy is currently the preferred treatment for severe carotid stenosis.
      The technique of eversion endarterectomy allows correction of severe vessel
      elongation and kinking. The latter is generally believed to be a relative
      contraindication for endovascular stent placement. We report successful
      percutaneous transluminal angioplasty and stenting of a left internal carotid
      artery with high-grade stenosis and severe kinking which was not amenable to
      endarterectomy because of the distal location of the stenosis. Advanced stent
      technology with flexible materials makes endovascular treatment of carotid
      stenosis feasible even in cases of kinking.

PMID- 11443411
TI  - Stent-graft repair of a splenic artery aneurysm.
AB  - We present a case of splenic artery aneurysm (SAA) treated with stent-grafts.
      This new method offers the benefit of preserving the blood flow through the
      splenic artery. This in turn allows for subsequent sequential embolization of the
      spleen when indicated, as in our patient with hypersplenism. This is the first
      reported case of stent-graft repair of SAA.

PMID- 11443412
TI  - Re: The malpositioned central venous catheter: a noninvasive technique for
      repositioning the catheter tip.

PMID- 11443413
TI  - Results and complications of laparoscopic cholecystectomy in childhood.
AB  - BACKGROUND: The purpose of our study was to evaluate the results and
      complications of laparoscopic cholecystectomy in a case series of 110 infants.
      METHODS: Over a 5-year period (1993-98), we performed laparoscopic
      cholecystectomy in 110 pediatric patients. Surgery was performed at different
      institutions by three different surgeons. The patient population was composed of
      69 girls and 41 boys; their ages ranged from 1 to 16 years (median, 8.5). All of
      the 110 children had symptomatic cholelithiasis, which was confirmed at
      ultrasound examination. An associated pathology was present in 27 patients
      (sickle cell disease in 17 cases, hereditary spherocytosis in seven cases,
      thalassemia in three); the other 83 infants were affected by idiopathic
      cholelithiasis. In 107 patients, the operation was performed using four ports; in
      three patients, it was done using five ports. In three patients, we also
      performed a concomitant splenectomy. RESULTS: Median duration of simple
      cholecystectomy was 45 min (range, 25-75) and hospital stay ranged from 1 to 10
      days (median, 2). Only 15 children required drainage. We had 17 complications in
      our series (15.5%), including a gallbladder perforation during dissection in 11
      patients, a fall of stones into the abdominal cavity during extraction in one
      patient, and a trocar orifice infection in the postoperative period in five
      patients. At a maximum follow-up of five years (range, 1-5), all patients were
      doing well. CONCLUSION: Laparoscopic cholecystectomy in children seems to be as
      effective as open surgery in cases of symptomatic cholelithiasis. In pediatric
      patients more than in adults, an accurate and precise dissection and a sound
      knowledge of possible congenital biliary abnormalities are essential to avoid any
      kind of complication.

PMID- 11443415
TI  - Trocar-site metastasis is not always due to laparoscopy.
AB  - The use of laparoscopic surgical techniques for the management of gynecologic
      malignancies has increased over the last years. Metastasis developing at the
      trocar insertion site is an emerging problem. We present the case of a 66-year
      old woman with endometrial cancer who was diagnosed with an umbilical tumor after
      laparoscopically assisted vaginal hysterectomy (LAVH) and bilateral
      salpingoophorectomy. The interval between LAVH and diagnosis of the umbilical
      tumor was 13 months. The tumor was excised, and metastasis of endometrial cancer
      was histologically confirmed. Review of computer tomograms taken before LAVH
      showed a tumor in the umbilical area that had not been recognized before therapy.
      Therefore, tumor manifestation at the abdominal wall after laparoscopic surgery
      should not automatically be considered the result of iatrogenic spreading.

PMID- 11443416
TI  - Laparoscopic placement of Tenchkoff catheters.

PMID- 11443418
TI  - Laparoscopic wedge resection for benign gastric tumors.
AB  - BACKGROUND: Both laparoscopic wedge resection and formal laparoscopic resection
      are used in the treatment of benign and malignant gastric diseases. METHODS: We
      performed totally laparoscopic wedge resection using stapling devices and three
      or four trocars. PATIENTS: Four patients were treated with this technique. All
      four suffered from gastrointestinal stromal tumors (GIST), and one presented with
      an additional gastric adenoma. Two were morbidly obese, and two had additional
      operations performed at the same time. Two patients were admitted for acute upper
      GI bleeding. RESULTS: All of the tumors were removed successfully. Operating time
      ranged from 135 to 215 min. Oral feeding commenced on days 2-4. Postoperative
      hospital stay ranged from 5 to 11 days. CONCLUSION: Laparoscopic wedge resection
      of benign gastric tumors is a safe, reliable method that should be further
      investigated and used on a broader scale.

PMID- 11443419
TI  - Azygos vein aneurysm as a diagnostic pitfall. The role of thoracoscopy.
AB  - We report the case of an azygos vein aneurysm that was found intraoperatively in
      a 66-year-old woman followed for esophageal carcinoma. She underwent video
      assisted thoracoscopy surgery (VATS) for biopsy of a mediastinal mass. This mass
      was diagnosed in the 2nd year of postoperative follow-up for a T2N0M0 esophageal
      carcinoma by computed tomography, which revealed a heterogeneous mass of ~2 cm in
      diameter in a retrotracheal location. Preoperative echoendoscopy demonstrated an
      extraesophageal lesion. A diagnostic thoracoscopy was done in order to exclude a
      metastatic lymph node disease.

PMID- 11443420
TI  - Experimental assessment of tumor growth and dissemination of a microscopic
      peritoneal carcinomatosis after CO2 peritoneal insufflation or laparotomy.
AB  - BACKGROUND: Based on clinical observations and previous animal studies,
      laparoscopic surgery for malignant disease is regarded as controversial. We used
      a rat model to measure and compare the tumor growth, proliferation, and
      dissemination of a microscopic peritoneal carcinomatosis after CO(2)
      intraperitoneal insufflation or laparotomy. METHODS: Peritoneal carcinomatosis
      was induced in three groups of 27 BD IX rats each with intraperitoneal injections
      of 106 DHD/K12 cells, an aneuploid tumor cell line. At 48 h after tumor cell
      injection, the animals were randomly divided into three groups to undergo
      different types of intervention. All animals were anesthetized for 20 min
      (Halothane). The control group had no surgical intervention (group C), group I
      had CO(2) insufflation (7 mmHg),and group L had a midline laparotomy (5-cm).
      Neither bowel manipulation nor any other traumatic action was performed. Two
      weeks later, the rats were killed and the incidence, type, and dissemination of
      carcinomatosis were evaluated. We also measured the tumor's weight. Malignant
      omentum was sampled for flow cytometry analysis (DNA ploidy, S-phase fraction).
      RESULTS: The incidence of carcinomatosis did not differ among the groups. The
      mean score of macroscopic characteristics of the carcinomatosis was 2.8 +/- 1.9
      in group L, 2.9 +/- 1.9 in group I, and 3 +/- 1.9 in group C (NS). The location
      of the implants did not differ, except for parietal peritoneum location, which
      was more frequent in group L (p < 0.01). The tumor weight was 4.96 g +/- 3.2 in
      group L, 5.55 g +/- 3.2 in group C, and 5.75 g +/- 3.4 in group I (NS). The
      percentage of aneuploid cells and S-phase fraction did not differ statistically
      among the groups. CONCLUSION: These results indicate that CO(2) insufflation does
      not cause more effects than laparotomy when tumors cells are present before the
      beginning of the surgery. Further studies are needed to determine the influence
      of other steps in laparoscopic surgery on tumor growth and dissemination.

PMID- 11443421
TI  - Cholecystoenteric fistula (CF) is not a contraindication for laparoscopic
      surgery.
AB  - BACKGROUND: Cholecystoenteric fistula (CF) is a rare complication of
      cholelithiasis. The aim of this study was to evaluate the safety and risk of
      complications when the laparoscopic approach is applied in patients with CF.
      METHODS: A questionnaire was mailed to all surgeons with experience of >100
      cholecystectomies working in Naples, Italy, and the neighboring area. RESULTS:
      Between February 1990 and May 1999, 34 patients presented with cholecystoenteric
      fistula (0.2% of >15,000 laparoscopic cholecystectomies performed in the same
      period). These patients were allocated into two groups: the LT group (those who
      underwent laparotomic conversion after the diagnosis of CF), which consisted of
      20 patients, four men and 16 women, with a mean age of 66.5 +/- 9.3 years (range,
      46-85) and the LS group (laparoscopically treated patients), which consisted of
      14 patients, three men and 11 women, with a mean age of 65.6 +/- 8.8 years
      (range, 51-74). They types of CF observed were as follows: in the former group of
      patients, cholecystoduodenal fistulas (n = 11, 55%), cholecystocolic fistulas (n
      = 5, 25%), cholecystojejunal fistulas (n = 3, 15%), and cholecystogastric
      fistulas (n = 1, 5%); in the latter group, cholecystoduodenal fistulas (n = 8,
      5.1%), and cholecystocolic fistulas (n = 4, 28.6) and cholecystojejunal fistulas
      (n = 2, 14.3%). Stapler closure of CF was done in four LT patients and three LS
      patients with cholecystoduodenal fistula; it was also done in three LT patients
      and three LS patients with cholecystocolic fistula. Hand-sutured fistulectomy was
      performed in six LT patients and three LS patients with cholecystoduodenal
      fistula, in two LT patients with cholecystocolic fistula, and in all patients
      with cholecystojejunal or cholecystogastric fistula. There were no deaths or
      intraoperative complications in either group. One patient in the LT group
      developed a bronchopneumonia postoperatively. Postoperative hospital stay was
      significantly longer in LT patients-17 +/- 4 vs 3+/-1 days (p < 0.001).
      CONCLUSION: Cholecystoenteric fistula is an occasional intraoperative finding
      during laparoscopic cholecystectomy. The results of this study, which are based
      on the collective experiences of 19 surgeons, illustrate the growing success of
      the laparoscopic approach to this condition, including a decreasing rate of
      conversion to open surgery over the last 3 years.

PMID- 11443422
TI  - Pneumoperitoneum with carbon dioxide and liver metastases.

PMID- 11443423
TI  - Does a laparoscopic approach to total abdominal colectomy and proctocolectomy
      offer advantages?
AB  - BACKGROUND: Controversy exists regarding the feasibility, safety, and outcomes of
      laparoscopic total abdominal colectomy (LTAC) and laparoscopic total
      proctocolectomy (LTPC). The object of this study was to assess the outcomes of
      LTAC and LTPC and compare them with those of institutional open procedure used as
      controls. METHODS: Perioperative data and surgical outcomes of patients who
      underwent TAC or TPC were analyzed and compared retrospectively at a single
      institution between 1991 and 1999. RESULTS: A total of 73 TACs performed during a
      9-year period were evenly distributed between laparoscopic (n = 37) and open (n =
      36) approaches. There were no significant differences between patient groups with
      respect to genders, age, weight, proportion of patients with inflammatory bowel
      disease, and the number of patients undergoing ileorectal anastomosis. The median
      operative time was longer with the laparoscopic method (270 vs 178 min; p =
      0.001), but the median length of hospital stay was significantly shorter (6 vs 9
      days; p = 0.001). The short-term postoperative complication rate up to 30 days
      from surgery was not statistically different (25% vs 44%; p = 0.137), although
      there was a clear trend toward a reduced number of overall complications in the
      laparoscopic group (9 vs 24). Wound complications were significantly fewer (0% vs
      19%; p = 0.015) and postoperative pneumonia was nonexistent in laparoscopic
      patients. Long-term complications also were less common in the laparoscopic group
      (20% vs 64%; p = 0.002), largely because of reduced incidence of impotence,
      incisional hernia, and ileostomy complications. Total proctocolectomy was
      performed laparoscopically in 15 patients and with an open procedure in 13
      patients over the same period. There were no statistically significant
      differences between the two groups with respect to gender, age, weight, and
      diagnosis. Median operating time was longer for the laparoscopic patients (400 vs
      235 min; p = 0.001), whereas the length of hospital stay, morbidity, and
      mortality were not significantly different. CONCLUSIONS: The results indicate
      that LTAC can be performed safely with a statistically significant reduction in
      wound and long-term postoperative complications, as compared with its open
      counterpart. Operating time is increased, but there is a marked reduction in
      length of hospital stay. Preliminary results demonstrate that LTPC also is
      technically feasible and safe, with equal morbidity, mortality, and hospital
      stay, as compared with open procedures. Studies with larger numbers of patients
      and a randomized controlled trial giving special attention to patient quality-of
      life issues are needed to elucidate the real advantages of this minimally
      invasive technique.

PMID- 11443424
TI  - The influence of intraoperative complications on adhesion formation during
      laparoscopic and conventional cholecystectomy in an animal model.
AB  - BACKGROUND: The aim of this study was to evaluate the extent of postoperative
      adhesion formation after laparoscopic and open cholecystectomy. MATERIALS AND
      METHODS: Qualified surgeons performed 60 experimental laparoscopic
      cholecystectomies (LC) in dogs with the aim to acquire the laparoscopic
      technique. To assess the relation between the complications during the operation
      (bleeding, laceration of the liver bed, or gallbladder perforation) and the
      formation of adhesions, surviving animals were divided into four groups according
      to the type of complication occurred. Assessment of the results was made by
      second-look laparoscopy 4 weeks after LC using the adhesion index (AI; score
      range, 0-4). The animals then were killed so the extent of adhesion formation
      could be measured. As a control, open cholecystectomy was performed in 15 dogs
      without intraoperative complications. The Mann-Whitney rank-sum test and Dunn's
      method were used for statistical analysis. RESULTS: No adhesion formation or
      intraoperative complications were registered in the laparoscopic group I. In all
      the cases wherein bleeding or laceration of the liver bed occurred and was
      managed with electrocoagulation, adhesions formed. Adhesion formation in these
      groups was significantly higher than in "ideal LC" or cases of gallbladder
      perforation alone (p < 0.01). All the animals in the control group developed
      significantly more adhesions than those in the experimental group (p < 0.05).
      CONCLUSIONS: It seems that LC has a lower rate of adhesion formation than the
      conventional open technique. Complications such as bleeding or laceration of the
      liver bed during LC can enhance adhesion formation. No adhesion formation can be
      mentioned in relation to gallbladder perforation during LC.

PMID- 11443425
TI  - Laparoscopic hernia repair in 2000. Update of the European Association for
      Endoscopic Surgery (EAES) Consensus Conference in Madrid, June 1994.
AB  - The 1994 meeting of the European Association for Endoscopic Surgery (E.A.E.S.) in
      Madrid highlighted a consensus-developing conference on the then new laparoscopic
      procedure for hernia repair. The conference was chaired by A. Paul from Cologne,
      Germany, and A. Fingerhut, from Poissy, France. The other members of the jury
      were B. Millat (France), L. Nyhus (USA), J. Himpens (Belgium), J.-L. Dulucq
      (France), V. Schumpelick (Germany), E. Laporte Rosello (Spain), C. Klaiber
      (Switzerland), J. Mouiel (France), P. Go (Netherlands), and J.-H. Alexandre
      (France). At that time, there were, in all, only three randomized trials
      available for analysis. Today, there are more than 60 trials and more than 12,500
      patients have been entered into them. An update, presented this year in Vienna,
      is summarized herein.

PMID- 11443426
TI  - Laparoscopic cholecystectomy in adults with sickle cell disease.
AB  - BACKGROUND: Chronic hemolysis predisposes adults with sickle cell disease (SCD)
      to the formation of bilirubinate cholelithiasis. METHODS: To study the impact of
      laparoscopic cholecystectomy (LC) on this groups, we reviewed our records of all
      patients with SCD and cholelithiasis treated electively from 1991 to 1999. During
      that period, 13 consecutive patients with SCD underwent elective LC for
      symptomatic cholelithiasis. Nine patients (69.2%) were managed with a
      preoperative transfusion regimen to achieve a hemoglobin value of >/=10 g/dl,
      independent of hemoglobin S percentage. Five patients who presented with jaundice
      were referred for preoperative endoscopic retrograde cholangiopancreatography
      (ERCP), which identified choledocholithiasis in two of them. Three other patients
      underwent intraoperative cholangiography, which revealed common bile duct stones
      in one patient. RESULTS: One patient developed pyrexia for 2 days. There were no
      vaso-occlusive crises or deaths. The mean hospital stay was 3.3 days.
      CONCLUSIONS: LC has proven to be a safe and efficacious method for the treatment
      of symptomatic cholelithiasis in this high-risk population. Hematologists are now
      more willing to refer early, well-prepared patients with SCD and uncomplicated
      gallbladder disease for elective LC.

PMID- 11443427
TI  - Understanding and optimizing laparoscopic videosystems.
AB  - As tactile feedback and degree of freedom for instrument movement are restricted
      in laparoscopic surgery, the video image plays the most crucial role in giving
      the surgeon information about the performance of the operation. The development
      of small, reliable, high-resolution imaging systems is essential for the
      surgeon's acquisition detailed information about the tissues being manipulated.
      Image quality depends on each component of the laparoscopic imaging unit. In this
      context, it is crucial for the surgeon to have an understanding of how the video
      signal is formed, transmitted, and displayed. Moreover, the surgeon also needs to
      have an idea about the basic principles and specifications of the surgical video
      systems (i.e. charge-coupled device (CCD) camera, monitors, and digitizers). This
      knowledge is essential for choosing pieces of equipment and knowing how to
      assemble them into a functional operating suite. The aim of this review is to
      provide the surgeon with the basics of video signaling, and to familiarize him or
      her with the technical principles of the surgical video systems. An insight into
      the future of laparoscopic video systems also is made, and practical tips for
      improving image quality and troubleshooting are given throughout the article.

PMID- 11443428
TI  - Obesity adversely affects the outcome of antireflux operations.
AB  - BACKGROUND: We hypothesized that obesity was associated with long-term failure of
      antireflux procedures, and that in obese patients antireflux operations were
      easier to perform via thoracotomy, and therefore likely to have a higher success
      rate than transabdominal (laparoscopic or open) antireflux procedures. The aims
      of this study was to determine the impact of obesity on the success of antireflux
      operations, and to compare the success rates of transthoracic and laparoscopic
      approaches in obese patients with gastroesophageal reflux. METHODS: The records
      of 224 consecutive patients undergoing antireflux surgery by two surgeons in a
      university-based tertiary care center were reviewed and patients contacted for
      follow-up assessment. The patients were classified into groups based on the type
      of operation performed and the calculated body mass index (BMI): normal (BMI 30).
      Recurrences were documented by symptoms responsive to acid-suppressive medication
      and radiologic or pH probe studies. RESULTS: Among the 224 patients included in
      this study, 187 underwent laparoscopic Nissen fundoplications (LNF) and 37
      underwent Belsey Mark IV(BM4) procedures. The mean follow-up period was 37
      months. The three groups included 89 (39.7%) patients classified as having normal
      weight, 87 (38.8%) as overweight and 48 (21.4%) as obese. Normal, overweight, and
      obese patients were similar in terms of age, gender, hiatal hernia size, degree
      of esophagitis, and comorbid conditions. A total of 26 recurrences occurred,
      giving an overall recurrence rate of 11.6%. There were 4 recurrences in the
      normal group (4.5%), 7 in the overweight group (8.0%; p not significant vs
      normal), and 15 in the obese group (31%; p < 0.001 vs normal; p <.001 vs
      overweight). The recurrence rate was similar between LNF and BM4 in each BMI
      subgroup, although in aggregate, the recurrence rate after BMW was greater than
      after LNF (10/37 vs 16/187; p < 0.02). CONCLUSIONS: Obesity adversely affects the
      long-term success of antireflux operations. Although athoracotomy provides
      optimal exposure of the hiatal structures in obese patients, a transthoracic
      approach was associated with a higher recurrence rate than LNF. Given the high
      failure rate of antireflux operations in obese patients, intensive efforts at
      sustained weight loss should be made before consideration of surgery.

PMID- 11443429
TI  - An unusual case of port site seeding.
AB  - We present an unusual case of a port site tumor from a colonic adenocarcinoma
      following laparoscopic cholecystectomy. A 66-year-old woman with a previous renal
      transplant underwent elective laparoscopic cholecystectomy for symptomatic
      cholelithiasis. Three months later, she re-presented with pain localized to the
      right lateral port wound. Subsequent investigation revealed an adenocarcinoma in
      the ascending colon with no evidence of local spread or liver metastases. The
      patient was enrolled in the ALCCAS trial (an Australasian multicenter prospective
      randomized clinical study comparing laparoscopic and conventional open surgical
      treatments of colon cancer in adults) and randomized to the laparoscopic arm. At
      laparoscopy, nodules of tumor were located at the sites of the previous right
      flank and umbilical trocar sites. The procedure was converted to an open
      hemicolectomy with excision of port sites. To our knowledge, only one other case
      of a colon carcinoma metastasizing to a port site following laparoscopic
      cholecystectomy has been reported. This case illustrates a number of points: (a)
      This was an advanced tumor at the time of diagnosis and was undoubtedly present
      at laparoscopic cholecystectomy. (b) This tumor was not manipulated at the time
      of laparoscopic cholecystectomy. (c) The patient was immunosuppressed at the time
      of laparoscopic cholecytstectomy. (d) The patient developed clinical recurrence
      in her laparotomy wound within 3 months of her open procedure. This case supports
      current arguments that the etiology of port site metastases is likely to be
      mulifactorial.

PMID- 11443430
TI  - Recurrent septic episodes following gallstone spillage at laparoscopic
      cholecystectomy.
AB  - A 51-year-old woman underwent emergency laparoscopic cholecystectomy. Stone loss
      occurred during gallbladder dissection. Histology showed empyema of the
      gallbladder. Postoperatively, she developed a subhepatic abscess that required
      percutaneous drainage. Two years after surgery, she re-presented with a right
      paracolic abscess. Transsciatic CT-guided drainage of the abscess was performed.
      Barium enema excluded colonic pathology. Two weeks later, she developed a right
      gluteal abscess deep to the recent drain site. Ultrasound-guided drainage was
      performed followed by a sonogram. The sonogram ruled out communication with the
      peritoneum. Two further subhepatic abscesses occurred during the next 5 years;
      the first abscess was drained percutaneously, but the second required open
      drainage: At laparotomy, gallstone fragments were found within the abscess
      cavity. The site of the previous gluteal drain continued to discharge
      intermittently. An MRI scan showed an uncomplicated sinus track. Subsequent
      sinography of the right gluteal track demonstrated an opacity at the apex of the
      sinus. The sinus was laid open and a gallstone retrieved. The patient has
      remained well for 3 years. Complications due to gallstone spillage generally
      manifest themselves shortly after surgery. This case demonstrates that lost
      stones may cause chronic abdominal and abdominal wall sepsis. In cases of chronic
      abdominal sepsis after laparoscopic cholecystectomy, the possibility of lost
      stones should be considered even if stones are not positively shown on imaging.

PMID- 11443431
TI  - Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of
      infancy.
AB  - BACKGROUND: A 4-week-old male infant (4.9 kg) with persistent hyperinsulinemic
      hypoglycemia of infancy (PHHI) underwent a laparoscopic pancreatectomy to
      evaluate its feasibility. Preoperative medications included diazoxide and
      glucagon to maintain adequate blood glucose levels. METHODS: Laparoscopic
      pancreatectomy was performed using a 5-mm cannula at the umbilicus, external
      fixation, transcutaneous suture-assisted gastric retraction to expose the lesser
      sac, and three additional 3.5-mm cannula sites. The pancreas was resected from
      the splenic hilum to the mesenteric vessels. The splenic vein was dissected from
      the under surface of the pancreas using electrocautery, and the spleen was easily
      preserved. Surgery time was 75 min, and minimal blood loss occurred. RESULTS: The
      child required no narcotic medication and tolerated a regular diet immediately
      after surgery. Serum glucose levels did decrease postoperatively, and the child
      required diazoxide, dextrose infusion, glucagon, and octreotide. On postoperative
      day 7, the child underwent an open near-total pancreatectomy, after which he
      remained asymptomatic. Essentially no scarring was found in the lesser sac, and
      the remaining pancreatic remnant was resected without difficulty. CONCLUSIONS:
      Laparoscopic pancreatectomy can be performed safely, even in a newborn patient,
      without prolonged operative time or unnecessary risk. The technique using
      external fixation and transcutaneous suture-assisted gastric retraction provides
      excellent exposure to the pancreas and lesser sac. In patients with PHHI, in whom
      reoperative additional pancreatectomy is very likely, this technique is the ideal
      initial surgical approach.

PMID- 11443432
TI  - Laparoscopic excision of duodenal tumors.
AB  - We present three patients with bleeding duodenal tumors who were managed by
      laparoscopic excision. This represents the largest study of such an experience.
      The literature is reviewed, and the various technical approaches are discussed.

PMID- 11443433
TI  - Successful emergency endometrial ablation for intractable uterine bleeding in a
      postmenopausal woman complicated with liver cirrhosis and morbid obesity.
AB  - Life-threatening intractable uterine bleeding is difficult to treat when
      concurrent medical complications contraindicate invasive surgery. We present a
      case of heavy uterine bleeding in a postmenopausal woman that was complicated by
      liver cirrhosis and morbid obesity. The bleeding was successfully halted through
      emergency endometrial ablation after failure of uterine artery embolization.

PMID- 11443434
TI  - Laparoscopic wedge resection of a gastric leiomyoma.
AB  - Gastric stromal tumors represent a small percentage of gastric neoplasms.
      Establishing a diagnosis when these lesions are encountered usually is not
      possible with limited biopsies. Benign and malignant gastric stromal tumors
      require only local excision for definitive treatment. However, most lesions are
      not amenable to endoscopic excision. As a result, laparoscopic local excision
      offers the ideal method to establish a diagnosis and to treat patients with
      gastric smooth muscle tumors. We present a minimally invasive local excision of a
      gastric stromal tumor. We also review the previously published management of
      gastric stromal tumors and show how it is being influenced by laparoscopy.

PMID- 11443435
TI  - Small bowel perforation from a migrated biliary stent.
AB  - Stenting of the biliary tract is performed for a variety of benign and malignant
      disorders. Although uncommon, proximal and distal migration of these stents is
      known to occur. We report a case of jejunal perforation from a distally migrated
      biliary stent.

PMID- 11443436
TI  - Minimally invasive retrieval of a foreign body after penetrating lung injury.
AB  - Minimally invasive techniques are increasingly used in the management of trauma
      victims. We report the case of a young man in a motor vehicle crash who sustained
      a penetrating wound to the anterior left chest caused by the automobile stick
      shift. Subsequent imaging demonstrated a large foreign body in the left lung. The
      foreign body was removed successfully by videothoracoscopy, and the patient made
      a full recovery. This case demonstrates the inroads that minimally invasive
      surgery is making in care of the injured and highlights an excellent technique
      for dealing with pulmonary foreign bodies.

PMID- 11443437
TI  - Thoracoscopic techniques in the management of benign mediastinal dumbbell tumors.
AB  - Mediastinal dumbbell tumors can be resected with a variety of open surgical
      approaches. Recently, thoracoscopic techniques have been suggested for the
      treatment of benign neurogenic lesions. Over a 5-year period, three patients with
      a benign mediastinal dumbbell tumor were treated via a combined
      microneurosurgical and thoracoscopic approach. The neurosurgical phase consisted
      of a posterior laminectomy to free the tumor from the spinal cord, followed by an
      intervertebral foraminotomy. Thoracoscopic resection of the lesion was then
      performed in the same setting. The operative times were 240, 260, and 280 min,
      and there were no operative complications. The postoperative stays were 6, 7, and
      7 days; the postoperative period was uneventful in all three patients. Pathologic
      examination revealed a benign schwannoma in two cases and an angiolipoma in one
      case. One patient reported the onset of paraesthesia in the left hypocondrium on
      the distribution area of the transected T10 and T11 intercostal nerves; slight
      paraesthesia still remains 15 months from surgery. We conclude that the combined
      posterior neurosurgical and thoracoscopic approach is a safe and effective method
      for the removal of benign mediastinal dumbbell tumors, whether neurogenic or
      nonneurogenic in origin.

PMID- 11443438
TI  - Incomplete large bowel obstruction caused by a duodenal stent.
AB  - Gastric outlet obstruction secondary to benign or malignant disease can be
      treated with self-expanding metallic stents. This obviates the need for surgical
      bypass procedures and returns most patients to a normal diet. Prosthesis
      displacement is described as a late complication. A case of stent migration to
      the rectum, presenting with the symptoms and signs of incomplete large bowel
      obstruction, is described.

PMID- 11443439
TI  - Palliation of a primary malignant melanoma of the distal esophagus by stent
      implantation. Report of a case.
AB  - BACKGROUND: A 55-year-old woman suffering from progressive dysphagia,
      retrosternal pain, and annoying foetor ex ore is described. Esophagogastroscopy
      showed a dark, necrotic tumor extending from 28 cm below the front teeth to the
      esophagogastric border, and biopsy showed it to be a primary malignant melanoma.
      The underlying progressive tumor stage with pericardial infiltration and intra
      abdominal lymph node metastasis precluded the possibility of curative surgical
      treatment. METHODS: For palliation, we implanted a metal stent (Ultraflex,
      Microvasive, Boston Scientific Corporation, Watertown, MA, USA) in the distal
      esophagus to alleviate the dysphagia. RESULTS: Permanent recanalization of the
      tumor-obstructed esophagus by stent implantation alleviates symptoms, thereby
      significantly improving quality of life. Radiochemotherapy can be performed
      despite the presence of the stent. CONCLUSIONS: Surgery is the therapy of choice
      for resectable primary malignant melanoma of the esophagus. Endoscopic therapy
      should be considered for alleviating dysphagia if surgery is impossible.

PMID- 11443440
TI  - Laparoscopic cholecystectomy in the new millennium.
AB  - BACKGROUND: Laparoscopic cholecystectomy has become the gold standard for the
      treatment of symptomatic cholelithiasis. Many authors-including investigators at
      our institution, who reported one of the initial experiences with laparoscopic
      cholecystectomy in July 1992-have documented a definite learning curve associated
      with this procedure. We present a follow-up study of our experience with
      laparoscopic cholecystectomy and compare these data to an earlier study of the
      initial experience with laparoscopic cholecystectomy at the Beth Israel Medical
      Center. METHODS: We retrospectively reviewed 300 consecutive patients from March
      1998 through March 1999. The patient population was epidemiologically similar to
      that of the original study with regard to age, sex, and American Society of
      Anesthesia (ASA) classification. However, whereas the initial population included
      only patients with chronic disease, in our study 13.7% of the patients had been
      admitted through the emergency room with acute stone disease of the biliary
      tract. RESULTS: We found a 5.7% conversion rate, a 1% rate of major complication,
      and a 5.7% rate of minor complication rates, as compared to the initial study's
      rates of 12%, 4%, and 10%, respectively. Whereas none of the patients in the
      original study left the hospital on the day of surgery and only 49% were
      discharged within 1 day, in our group, 29 patients (10%) underwent ambulatory
      procedures and an additional 186 patients (62%) were discharged on the 1st post
      operative day. The average duration of the operation was 90 min, which did not
      represent a statistical improvement over the time of 93 min reported in the
      earlier study. CONCLUSIONS: Since 1992, both the conversion rate and length of
      stay have declined at our hospital, but operative time has remained essentially
      the same. These findings probably reflect a bimodal learning curve, the increase
      in the number of cholangiograms and additional intraoperative procedures now
      performed, the greater severity of gallbladder disease currently treated with
      laparoscopic cholecystectomy, and increases in the number of attending physicians
      as well as the level of residents who perform this procedure.

PMID- 11443441
TI  - Laparoscopic management of malfunctioning peritoneal dialysis catheters.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) is an established
      alternative method to hemodialysis for treating end-stage renal disease patients.
      However, this method is associated with a significant number of complications,
      such as catheter malposition, omental wrapping, and infection. The purpose of
      this study was to determine the efficacy of laparoscopy in the treatment of
      malfunctioning CAPD catheters. METHODS: Between November 1994 and June 1999, a
      total of 16 patients with CAPD underwent laparoscopy for the evaluation and
      management of CAPD catheter dysfunction. Two trocars (10-mm and 5-mm) were used.
      Recorded data included patient demographics, catheter implantation method, date
      of malfunction, cause of dysfunction, procedure performed, complications, and
      catheter outcome. RESULTS: The primary etiology of dysfunction was omentum and/or
      small bowel wrapping with adhesions in eight cases, malpositioning in five cases,
      and infection in the remaining three cases. Adhesiolysis was performed in the
      eight cases with adhesions. In the five cases with malpositioning but no
      adhesions, the catheters were repositioned in the pelvic cavity. Two catheters
      had to be withdrawn because of infection. In one case with tunnel infection, the
      catheters were exchanged simultaneously. There was only one perioperative
      complication, consisting of temporary dialysate leakage. There were no mechanical
      or infection problems. The overall success rate of catheter function (>30 days
      after laparoscopy) was 100%, except for two cases in which the catheters had to
      be removed. CONCLUSION: Laparoscopy is a highly effective and successful method
      for the evaluation and management of peritoneal dialysis catheter dysfunction.

PMID- 11443442
TI  - Increased platelet-derived growth factor (PDGF) release after laparotomy
      stimulates systemic tumor growth in mice.
AB  - BACKGROUND: Our laboratory has demonstrated that tumors grow larger and are more
      easily established following laparotomy than after carbon dioxide (CO2)
      pneumoperitoneum or anesthesia alone. We have also shown that tumor cells
      incubated with serum from laparotomized mice proliferated significantly faster in
      vitro than those incubated with plasma from mice that underwent laparoscopy or
      anesthesia alone. We hypothesized that differing levels of a plasma-soluble
      growth factor(s) postoperatively causes tumors to proliferate faster after
      laparotomy. This study's purpose was to isolate and characterize the plasma
      growth factor(s) responsible for the increased growth of systemic tumors after
      laparotomy. METHODS: Female Balb/C mice (n = 100) were randomized to two groups:
      anesthesia control (AC) or midline sham laparotomy (4 cm) (Open). Plasma was
      collected on Postoperative day 4. For the tumor proliferation assay, C-26 colon
      cancer cells were incubated in media with either 10% AC or Open "raw" plasma (not
      passed through column), or AC or Open plasma that had been passed through the
      column. For elution of heparin-binding proteins, plasma from each group was
      passed through a heparin-sepharose column. Elution of bound proteins was
      accomplished with a 0.1-2 M NaCl gradient. Each fraction was examined for protein
      content. For the anti-platelet-derived growth factor (PDGF) neutralizing antibody
      study, C-26 cells were incubated with one of four plasma preparations: AC or Open
      plasma alone, or AC or Open plasma incubated with anti-PDGF antibody. For both
      studies, tumor proliferation was determined after 2 days with an MTS/PMS assay.
      Results from each group were compared and differences determined using analysis
      of variance (ANOVA) and Tukey-Kramer tests. RESULTS: On heparin chromatography, a
      single elution peak consistent with PDGF was present in both AC and Open plasma
      and was 1.5 times greater in the Open plasma. The first tumor proliferation assay
      showed that tumor cells incubated with Open plasma proliferated 2.5 times faster
      than those with AC plasma (p < 0.0001). Passage of AC plasma through the column
      did not alter its mitogenic activity, but Open plasma thus treated demonstrated
      significantly decreased mitogenic activity. The second tumor proliferation assay
      showed that anti-PDGF antibody had no effect on the mitogenic activity of the AC
      plasma but decreased the mitogenic activity of the Open plasma to the AC plasma
      level. CONCLUSIONS: Laparotomy is associated with higher levels of a heparin
      binding plasma factor, consistent with PDGF. The enhanced mitogenic activity of
      the OP plasma was neutralized with anti-PDGF antibody. Increased plasma levels of
      PDGF after laparotomy may be responsible for accelerated tumor growth following
      laparotomy in mice.

PMID- 11443443
TI  - Initial results with an electrothermal bipolar vessel sealer.
AB  - BACKGROUND: An electrothermal bipolar vessel sealer (EBVS; Ligasure, Valleylab,
      Boulder, CO, USA) was developed as an alternative to suture ligatures, hemoclips,
      staplers, and ultrasonic coagulators for ligating vessels and tissue bundles. The
      EBVS seals vessels up to 7 mm in diameter by denaturing collagen and elastin
      within the vessel wall and surrounding connective tissue. This study is the first
      to determine the clinical efficacy and safety of this instrument and delineate
      its potential timesavings in both experimental (animal) and clinical scenarios.
      METHODS: A prospective review of the author's clinical experience with the EBVS
      in laparoscopic and open operations from October 1998 to March 2000 was
      performed. In addition, five Yorkshire domestic pigs underwent 150-cm small
      intestine resections (n = 10) using the EBVS (n = 5) and suture ligatures (n =
      5). Measurements included time to complete intestinal resection, the number of
      applications per minute for each method, and the presence of postapplication
      bleeding. Statistical analysis was performed using Student's t-test. RESULTS: The
      EBVS was used in 98 cases (46 laparoscopic and 52 open) with a mean of 43
      applications (range, 10-150 applications) per case. The operations included 53
      colon and/or small bowel resections (54.1%), 24 fundoplications (24.5%), 12
      gastric resections (12.2%), 3 splenectomies, 2 pancreatectomies, 1 adrenalectomy,
      1 bilateral salpingo-oopherectomy, 1 pancreatic cyst-jejunostomy, and 1 vagotomy
      with gastrojejunostomy. In all these cases, the EBVS was intended to be the only
      means of vessel ligation. An alternative ligation technique was required for
      bleeding in only 13 (0.3%) of more than 4,200 applications of the EBVS. No
      postoperative hemorrhagic complications occurred. There was an estimated mean
      reduction in operative time of 39 min per open procedure, and a mean prolongation
      in operative time of 8 min per laparoscopic procedure when the EBVS was used in
      lieu of suture ligatures, hemoclips, staplers, or ultrasonic coagulators. In the
      animal model, the mean time for completion of the intestinal resection was 251.9
      s for the EBVS and 702.0 s for ligatures (p < 0.001). The mean number of
      applications per minute was 7.6 for the EBVS and 1.8 for ligatures (p < 0.001).
      No postapplication bleeding was seen. CONCLUSIONS: Initial clinical results from
      the use of EBVS in laparoscopic and open procedures demonstrate it to be safe and
      effective, reducing operative time in open procedures. Suture ligatures, ties,
      hemoclips, and other ligating techniques were used rarely (0.3%) after an
      application of the EBVS. In an experimental animal model, the EBVS was
      significantly faster and more efficient (more applications per minute) than
      ligatures for intestinal resection.

PMID- 11443444
TI  - Converted laparoscopic colorectal surgery.
AB  - BACKGROUND: Conversion rates following laparoscopic colorectal surgery vary
      widely between studies, and the outcome of converted patients remains
      controversial. METHODS: A comprehensive search of the English-language literature
      was updated until May 1999. RESULTS: Twenty-eight studies on 3232 patients were
      considered for analysis. The overall conversion rate was 15.38%. Seventy nine
      percent of the studies did not include a definition for conversion; in these
      studies, the conversion rate was significantly lower than in the series where a
      specific definition was considered (13.7% vs 18.9%, chi-square test, p < 0.001).
      Converted patients had a prolonged hospital stay (11.38 vs 7.41 days) and
      operative time (209 vs 189 min) in comparison with laparoscopically completed
      patients (95% confidence interval (CI), 1.70-4.00 and 35.90-37.10, respectively).
      The factors associated with an increased rate for conversion were left colectomy
      (Odds Ratio [OR] = 1.061), anterior resection of the rectum (OR = 1.088),
      diverticulitis (OR = 1.302), and cancer (OR = 2.944) (for each parameter, Wald
      chi-square value, p < 0.001). CONCLUSIONS: In nonrandomized studies, the rate of
      laparoscopically completed colorectal resections is close to 85%. Because
      converted patients have a distinct outcome, a clear definition of conversion is
      required to compare the results of randomized trials. Such trials should also
      consider a 20% rate of conversion when estimating the sample size for the desired
      power level. It is likely that converted patients will have a significant impact
      on the results of future clinical research in laparoscopic colorectal surgery.

PMID- 11443445
TI  - Evaluation of endoscopic and laparoscopic training practices in surgical
      residency programs.
AB  - BACKGROUND: The ability to adequately train surgical residents in flexible and
      rigid endoscopy has become a difficult challenge for program directors. The
      American Board of Surgery requires residents to be familiar in these procedures
      but the methods for training have not been well defined nor formally outlined.
      The goals of this study were to evaluate resident experience in flexible
      endoscopy and laparoscopy and to investigate the specific methods used by
      surgical programs for the training of residents. METHODS: A survey was created by
      the authors and the Resident Education Committee of the Society of American
      Gastrointestinal Endoscopic Surgeons and was mailed to all program directors in
      general surgery in the United States based on the data base of the Association of
      Program Directors in Surgery (APDS). RESULTS: Ninety-six of 283 surveys were
      returned (33.9%). The surgeon played a greater role in flexible endoscopic
      training in 1998 as compared to 1988 (p=0.002). When analyzed by type of
      institution, community programs showed a similar trend but this was not seen in
      academic programs. Formal endoscopy rotations existed in 60% of programs but
      flexible endoscopy (5.2%) and laparoscopy (10.4%) fellowships were uncommon. No
      significant differences in the number of advanced laparoscopic procedures
      performed were found between academic and community programs. The presence of a
      laparoscopic fellow did not significantly decrease the number of cases per
      resident. CONCLUSION: According to our survey, surgery departments have a greater
      impact on flexible endoscopic training in 1998 than in 1988. This is likely due
      to the creation of formal endoscopy rotations and the hiring of fellowship
      trained endoscopic instructors. In addition, community programs have been able to
      provide adequate experience in both basic and advanced laparoscopic techniques as
      compared to academic programs. As with flexible endoscopy, however, formal
      laparoscopic rotations may be necessary to allow more intensive experience for
      each resident.

PMID- 11443447
TI  - A unified approach to recurrent laparoscopic hernia repairs.
AB  - BACKGROUND: The problem of recurrence after laparoscopic hernia repair is
      relatively new, and the best way to handle it remains uncertain. The question of
      whether an open approach, a laparoscopic approach, or some combination of
      techniques should be preferred has not yet been resolved. The purpose of this
      study was to determine if the laparoscopic approach could deal with the problem
      safely and successfully. METHODS: A retrospective review was done of the cases
      performed at the Center for Hernia Repair by one surgeon between July 1991 and
      September 1999. Laparoscopic hernioplasties for hernias that had previously been
      repaired laparoscopically were analyzed. All remedial repairs were begun using a
      transabdominal approach. RESULTS: Seventeen of 1960 hernias repaired were for
      failed laparoscopic repairs. Ten were repaired totally laparoscopically and two
      via an open approach with mesh, while five required a small anterior
      counterincision. There were no serious complications and one recurrence.
      CONCLUSION: The laparoscopic transabdominal approach to failed laparoscopic
      repairs is feasible, safe, and reliable when used in combination with a modified
      anterior approach when appropriate.

PMID- 11443448
TI  - Diagnostic laparoscopy and laparoscopic ultrasonography optimize the staging and
      resectability of intraabdominal neoplasms.
AB  - BACKGROUND: Despite technical improvements, preoperative imaging studies often
      fail to predict intraoperative findings. We investigated the potential use of
      diagnostic laparoscopy (DL) and laparoscopic ultrasonography (LUS) for the
      assessment of disease in patients with abdominal neoplasms. METHODS: Fifty
      consecutive patients with abdominal neoplasms underwent spiral computed
      tomography with oral and intravenous contrast using 5-mm contiguous sections. In
      addition, eight patients underwent ultrasonography, six underwent magnetic
      resonance imaging, and eight underwent positron emission tomography. All patients
      then underwent DL and LUS using a 7.5-MHz ultrasound probe. RESULTS: There were
      29 men and 21 women with a mean age of 63 years (range, 35-84). Most had a
      diagnosis of colorectal cancer (19 cases), melanoma (12 cases), or hepatoma (five
      cases). In nine cases (18%), DL revealed peritoneal metastatic implants not shown
      on preoperative images. In 18 cases (36%), LUS was more accurate than
      preoperative imaging. Combined DL and LUS findings radically changed the
      operative management in 16 patients (32%). CONCLUSION: As compared with
      preoperative imaging, the combination of DL and LUS provides more accurate
      information regarding staging and resectability. Moreover, it helps to determine
      the extent of operation and reduces the number of unnecessary laparotomies. DL
      and LUS should be used as an adjunct to preoperative imaging studies in patients
      with primary or metastatic intraabdominal neoplasms.

PMID- 11443449
TI  - Extraperitoneal laparoscopic hernia repair with local anesthesia.
AB  - BACKGROUND: This review aimed to compare laparoscopic preperitoneal herniorrhaphy
      (LPPH) using a laryngeal mask airway and local anesthesia with conventional open
      herniorrhaphy using similar anesthetic conditions. METHODS: A retrospective
      review of 238 hernia operations was conducted from October 1996 through September
      1998. Laparoscopic preperitoneal hernia repairs with the patient under laryngeal
      mask airway anesthesia were performed initially using 10 ml of 0.5% bupivacaine
      (LPPH+10 group). This was compared with hernia repair using 30 ml of 0.5%
      bupivacaine (LPPH+30 group). Both LPPH groups were compared with a plug and patch
      "Gilbert" hernia repair group. Postoperative pain was compared in the recovery
      room and outpatient suite. RESULTS: The LPPH+30 group required significantly less
      postoperative pain medication than the LPPH+10 group. The LPPH+30 group required
      slightly more pain medication in the recovery room than the open hernia repair
      group, but in the postanesthesia care unit (PACU) unit, the LPPH+30 group used
      less pain medication. A similar number of LPPH+30 patients, and open hernia
      repair patients required no pain medication. CONCLUSIONS: The use of a long
      acting local anesthetic, (30 ml of 0.5% bupivacaine via laryngeal mask airway)
      for laparoscopic preperitoneal hernia repair compared favorably with conventional
      open hernia repair using similar anesthetic techniques.

PMID- 11443450
TI  - Technique for using pledgeted sutures in laparoscopic Nissen fundoplication.

PMID- 11443451
TI  - Laparoscopic antireflux surgery at an outpatient surgery center.
AB  - BACKGROUND: Laparoscopic fundoplication (LF) procedures have been shown to be
      safe and effective for the control of gastroesophageal reflux disease (GERD).
      Preliminary reports suggest that LF can be performed safely in an ambulatory
      surgery center. We report on our extensive experience with outpatient LF.
      METHODS: Since May 1995, we have performed laparoscopic antireflux procedures in
      557 consecutive patients at a freestanding outpatient surgery center. All
      patients had esophageal manometrics and esophagogastroduodenoscopy (EGD) within 1
      year of their surgical procedure. This series included 16 patients with large
      paraesophageal hernias (mostly type III) and 22 patients with prior antireflux
      procedures. Most patients (n = 494) underwent Nissen fundoplication. RESULTS:
      Patients were typically given clear liquids 6 hs postoperatively and discharged
      home in

PMID- 11443452
TI  - Trocar site recurrence in laparoscopic surgery for colorectal cancer.
AB  - BACKGROUND: Laparoscopic colorectal surgery has been associated with less
      postoperative pain, an early return of bowel function, a shorter period of
      hospitalization and disability, and better cosmetic results. However, the
      application of laparoscopic techniques to the curative resection of colorectal
      cancer is still controversial, owing to reports of cancer recurrence at the port
      site wounds. The accumulation of numerous such reports in a relatively short
      period raised concern that there might be an extraordinary high rate of port site
      metastases after laparoscopic colorectal surgery. This concern has led to intense
      clinical and basic research aimed at determining the incidence and causes of
      wound recurrence and developing preventative measures to address this problem.
      Despite these efforts, it is still not clear whether port site metastasis is
      really an inherent drawback to laparoscopic cancer surgery. METHODS: In this
      review of the literature on port site metastasis, we gathered data from clinical
      series of laparoscopic surgery for colorectal cancer. We eliminated series of <50
      patients, since they may be flawed by the learning curve required for this
      technically demanding procedure. RESULTS: The rate of port site recurrences in
      the 1737 patients who participated in these series was 1%. Although the methods
      and criteria for patient selection in these studies varied, this figure appears
      to be comparable to the incidence reported for other malignancies and for
      laparotomies performed to treat colorectal cancer. CONCLUSION: This review
      suggests that wound recurrence may actually be the result of an unfortunate
      learning curve, rather than an inherent concern. However, we must await the final
      results of large randomized studies before drawing any definitive conclusions.

PMID- 11443453
TI  - Automated high-frequency posture sampling for ergonomic assessment of
      laparoscopic surgery.
AB  - BACKGROUND: Despite widespread acknowledgement that strain injuries do occur to
      surgeons, ergonomic assessments in minimally invasive surgery are comparatively
      rare. Current assessment techniques rely on labor-intensive manual recording
      techniques, so there is a need for an automated system. METHODS: We used an
      optoelectronic measurement system to make postural measurements at frequencies of
      ~5 Hz and then converted these measurements to ergonomic stress scores using a
      modified Rapid Upper Limb Assessment (RULA) method. RESULTS: We successfully
      recorded postures at least once per second during 96% of the time the surgeon was
      performing tissue manipulation tasks. We found that the ergonomic stress scores
      were comparatively high throughout the procedure, particularly for the wrist.
      CONCLUSION: An automated high-frequency postural measurement system is feasible
      for making ergonomic assessments in an intraoperative setting. Such a system will
      also be a critical component in validating surgical simulations for use in
      training and credentialing surgeons and in designing and evaluating equipment.

PMID- 11443454
TI  - Alterations in hemodynamics and hepatic and splanchnic circulation during
      laparoscopy in rats.
AB  - BACKGROUND: There is growing evidence that a pneumoperitoneum with increased
      intraabdominal pressure exerts adverse cardiovascular and splanchnic circulatory
      effects, whereby portal blood flow, in particular, is disturbed. METHODS:
      Cardiovascular hemodynamics and the blood flow of hollow viscus and solid organs
      were evaluated in rats undergoing laparotomy, followed by diagnostic carbon
      dioxide (CO2) laparoscopy with an intraabdominal pressure of either 4 or 10 mmHg
      and rapid desufflation of the abdominal cavity. The method we employed used g
      labeled microspheres and conventional hemodynamic measurements. RESULTS: During
      CO2 laparoscopy, cardiac output and mean arterial pressure were significantly
      reduced to between 20.5% and 25% and 14.8% and 18% respectively. After rapid
      desufflation, cardiovascular hemodynamics normalized to baseline values. During
      laparoscopy, blood flow in the hollow viscus organs was less disturbed than that
      in the solid organs. Although small and large bowel blood flow was reduced
      significantly (26.6% and 23.9%, respectively), gastric blood flow remained
      unchanged. The decreases in the liver, spleen, pancreas, and kidney circulation
      were 29-37.2%, 37.6-64.6%, 51.2-57.5%, and 34.8-40.6%, respectively. Total
      hepatic blood flow was influenced predominantly by portal blood flow, which was
      particularly decreased; hepatic arterial flow remained stable. CONCLUSIONS:
      Severe alterations in cardiovascular hemodynamics, and to hepatic and splanchnic
      circulation occur rapidly during CO2 laparoscopy. It can be presumed that both
      increased intraabdominal pressure and hypercapnia are the main factors underlying
      these disturbances.

PMID- 11443455
TI  - Laparoscopy and the internet. A surgeon survey.
AB  - BACKGROUND: The Internet has become an important new tool for the delivery and
      acquisition of medical information. METHODS: A 13-item questionnaire designed to
      collect information on the attitudes and practices of surgeons regarding the use
      of the Internet as a medical resource was posted on the World Wide Web and also
      sent via e-mail. RESULTS: Over a 2-month period, 459 surgeons were enrolled in
      this study. Most of the respondents were identified as male surgeons (96%)
      between the ages of 31 and 50 years (79.25%). They accessed the Internet mainly
      from their homes (67.10%) and offices (17%) using 56 Kbps (34.86%) and 33.6 Kbps
      (21.79%) modems. These participants indicated that they use the Internet to
      expand their knowledge of general surgery (78.87%), learn more about technologies
      related to the practice of surgery (74.51%), access the Medline medical database
      (73.20%), and locate other resources for academic purposes (68%). Approximately
      half of them said that they favored the use of robotic assist devices in the
      operating room (53%), and most supported the use of technology for telementoring
      purposes (78%). Almost 80% professed an interest in video streaming technology
      applied to surgical education. CONCLUSIONS: This study showed that the Internet
      is a useful and powerful real-time survey tool that can help us to assess the
      impact of the World Wide Web and related technologies on surgical education and
      practice. However, the respondents in this study belong to a biased group that is
      already familiar with the Internet and computer technology and thus may not be
      representative of the surgical community as a whole.

PMID- 11443456
TI  - Thoracoscopic surgery and conventional open thoracotomy in metastatic lung
      cancer.
AB  - BACKGROUND: We performed a retrospective comparison of the oncological outcome of
      thoracoscopic surgery for pulmonary metastasis with that of conventional open
      thoracotomy. METHODS: The patient population for our retrospective comparison was
      comprised of 45 patients undergoing pulmonary resections via video-assisted
      thoracoscopy (thoracoscopy group) and 55 undergoing similar resections by open
      thoracotomy (open group) for pulmonary metastases between 1994 and 1999. RESULTS:
      Solitary metastasis was resected more frequently with thoracoscopy than open
      thoracotomy. There were no significant intergroup differences in rates of local
      recurrence from the initial pulmonary resection site. The actuarial 1-year, 2
      year, and 3-year survival rates were, respectively, 82.8%, 70.0%, and 62.3% in
      the thoracoscopy group and 93.6%, 64.6%, and 52.7% in the open group. The rates
      of pulmonary recurrence and survival also did not differ significantly between
      the two groups with solitary metastases. CONCLUSION: Thoracoscopic surgery for
      metastatic lung disease appears to be feasible as long as the preoperative
      metastatic tumor evaluation using chest computed tomography (CT) is accurate.

PMID- 11443457
TI  - Intraoperative cholangiography in laparoscopic cholecystectomy during residency
      in general surgery.
AB  - BACKGROUND: The role of laparoscopic intraoperative cholangiography (IC) in the
      diagnosis of asymptomatic choledocholithiasis is still controversial. The aim of
      this study was to evaluate the diagnostic-therapeutic impact and the educational
      implications of this method for residents specializing in general surgery.
      METHODS: We reviewed the records of 835 patients who underwent laparoscopic
      cholecystectomy for cholecystolithiasis without choledocholithiasis. IC was
      routinely performed by both expert surgeons and residents in general surgery.
      RESULTS: The cholecystectomy was completed laparoscopically in 804 cases, but
      conversion to open surgery was required in 31 cases. IC was not completed in 140
      cases (17.4%), and in 44 cases it revealed a suspected choledocholithiasis. The
      stones were treated via laparoscopy in 36 cases, laparotomy in six cases, and
      endoscopic retrograde cholangiopancreatography (ERCP) in two cases. Five patients
      were not diagnosed wit h choledocholithiasis. In one case, a lesion of the
      choledochus was discovered and treated laparoscopically. A total of 610 IC were
      done by expert surgeons and 225 by residents. The duration of the cholecystectomy
      with IC was significantly different between the two groups (76.9 +/- 12 vs 92.4
      +/- 11), as was the feasibility index (88.6% vs 80.6%). CONCLUSIONS: Laparoscopic
      IC is a safe and accurate procedure for the diagnosis of unrecognized
      choledocholithiasis. Teaching of this procedure as part of the specialization in
      general surgery would be opportune because it would provide surgical residents
      with an additional tool for the diagnosis and treatment of this pathology of the
      common bile duct.

PMID- 11443458
TI  - Effects of CO2 pneumoperitoneum on the basilar artery.
AB  - BACKGROUND: Laparoscopic surgery provides many benefits to the patients. The
      purpose of this study was to evaluate cerebral blood flow changes and the
      possibility of ischemia-reperfusion injury occurring during carbon dioxide
      (CO(2)) pneumoperitoneum. METHODS: Forty-eight New Zealand white rabbits were
      divided into four experimental and two control groups. Rabbits were subjected to
      CO(2) pneumoperitoneum with an intraabdominal pressure of 8 and 15 mmHg for 60 or
      180 min as designed for experimental groups. We then assessed the changes in
      physiological and transcranial Doppler ultrasonographic parameters, as well as
      brain malondialdehyde levels. RESULTS: Transcranial Doppler sonography of the
      basilar artery revealed elevated mean velocity and decreased resistance index and
      pulsatility index values with the longer-duration and higher-pressure CO(2)
      pneumoperitoneum. However, there were no statistically significant difference in
      m alondialdehyde values. CONCLUSION: Elevated intraabdominal pressure by CO(2)
      pneumoperitoneum, which does not lead to ischemia-reperfusion injury of the brain
      tissue, results in increased cerebral blood flow and reduced cerebrovascular
      resistance as an autoregulatory cerebral answer for CO(2).

PMID- 11443459
TI  - Abdominal malignancies missed during laparoscopic cholecystectomy.
AB  - BACKGROUND: We present our experience with intra-abdominal malignancies different
      from gallbladder cancer not diagnosed preoperatively and undiscovered during
      laparoscopic cholecystectomy METHODS: This study involved retrospective analysis
      of 10 patients hospitalized in the Second Department of General Surgery between
      1993 and 2000. In all of them, laparoscopic cholecystectomy had been performed
      between one week and 21 months earlier. RESULTS: Primary or metastatic neoplasms
      were diagnosed in five men and five women patients ages 38 to 79 years. In three
      patients with colorectal cancer, a radical resection was possible. Nonresectable
      pancreatic cancer was found in three patients. In one of two patients with
      gastric cancer, palliative, distal gastrectomy was performed. In a patient who
      had small bowel cancer with metastasis to the ovary, a radical operation was
      possible. In one patient, liver metastasis from lung cancer was found.
      CONCLUSIONS: In patients with atypical symptoms of gallbladder lithiasis, a
      thorough workup before laparoscopic cholecystectomy should be performed. During
      the laparoscopic procedure, a detailed examination of the whole peritoneal cavity
      is essential. In cases of prolonged convalescence after laparoscopic
      cholecystectomy, a source of symptoms different from cholelithiasis should be
      suspected.

PMID- 11443460
TI  - The Z-line appearance and prevalence of intestinal metaplasia among patients
      without symptoms or endoscopical signs indicating gastroesophageal reflux.
AB  - BACKGROUND: A four-graded classification of the Z-line appearance (ZAP) has been
      proposed, which was shown to correlate with the prevalence of intestinal
      metaplasia (IM) among patients with gastroesophageal reflux disease (GERD). The
      aim of this study was to determine the ZAP grade and the prevalence of IM among
      patients without GERD. METHODS: In this study, 53 consecutive patients without
      signs or symptoms of GERD were included. RESULTS: A normal Z-line (ZAP grade 0)
      was found in 26 patients (51%), and this group had a lower prevalence of
      Helicobacter pylori infection and atrophy in the cardia than ZAP grade patients.
      The non-GERD patients in this study had less ZAP pathology than the GERD patients
      in our previous study. Intestinal metaplasia at the Z-line, observed in 17% of
      the patients, was found to associate with peptic ulcer and carditis. CONCLUSION:
      The normal Z-line is feasibly defined as ZAP grade 0.

PMID- 11443461
TI  - Evaluation of a head-mounted display (HMD) in the performance of a simulated
      laparoscopic task.
AB  - BACKGROUND: Head-mounted display (HM) units are used in various industries, but
      they have been tried only recently in surgery. In this study, we evaluated
      whether a commercially available HMD would improve or impede a laparoscopic task
      in this case, suturing. METHODS: Six participants performed a total of 120
      laparoscopic suture knots in an experimental model. The Olympus FMD011 model with
      a two-dimensional image was used. The order of each task with or without the head
      display unit was random. The time to complete each knot was recorded, and the
      results were analyzed. RESULTS: The display unit prolonged the suturing times of
      the subjects by 10% (p < 0.04). CONCLUSIONS: In this experimental model, the HMD
      we utilized did not appear to improve laparoscopic suturing. More developments,
      such as improved depth perception and better resolution, may increase its
      usefulness for laparoscopic tasks.

PMID- 11443462
TI  - Validation of a new experimental model of colon cancer.
AB  - BACKGROUND: Most of the published animal studies that have evaluated tumor growth
      and port site metastases in laparoscopy have utilized a cell suspension model and
      thus cannot be compared to the clinical situation. Although solid tumor models
      have been developed, there has been no experimental model that establishes an
      orthotopic tumor in the rectum, reflecting the clinical situation of a solid
      colonic cancer. METHODS: Tumor cells (colon adenocarcinoma DHD/K1/TRb) were
      administered intraperitoneally in rats, which were used as solid tumor donors. A
      20-mg piece of solid tumor from the donor was placed in a submucosal blister
      created in the rectum wall of the study rats. The approach to the submucosal
      blister was made through the mucosa after contralateral enterotomy. In order to
      validate the model, this intervention was performed in 10 cases (group A). After
      10 days of intervention, the rats were submitted to resection of the rectum and
      histological examination of the specimen. In another 10 rats (group B),
      manipulation of the tumor was performed after 10 days to cause tumor cell
      spillage. The likelihood of tumor dissemination was investigated in this group 20
      days after this intervention. RESULTS: Group A developed solid tumors in seven of
      10 cases (70%). All of the tumors were localized between the muscular and the
      mucosal layer, with preservation of the serosa and without affecting the
      enterotomy. In all of the rats in group B, macroscopic tumor was observed in the
      upper rectum (100%) 10 days after its induction. Twenty days after tumor
      manipulation, nine rats had local tumor dissemination; two of them also had
      general tumor dissemination in the abdominal cavity. CONCLUSIONS: We established
      a novel solid colonic tumor model in rats for the investigation of intraoperative
      tumor cell spillage during resection of the colon and the development of port
      site metastases.

PMID- 11443463
TI  - A proteinase inhibitor decreases tumor growth in a laparoscopic rat model.
AB  - BACKGROUND: The balance between proteolysis and protease inhibition in the
      formation and breakdown processes of the extracellular matrix plays a major role
      in tumor cell invasion. An understanding of this relationship gave rise to the
      therapeutic concept of lowering tumor cell invasion by inhibiting protease
      activity. Phosphoramidon is an unspecific proteinase inhibitor. This experimental
      study investigated the effect of intraperitoneal phosphoramidon administration on
      tumor growth in a laparoscopic rat model. METHODS: In the first phase of the
      study, we investigated the influence of phosphoramidon on tumor cell invasion in
      a collagen matrix gel chamber in vitro. In a second experiment, a suspension of
      colon carcinoma cells (CC531) was introduced into the peritoneal cavity of male
      WAG rats. Prior to laparoscopy (at 6 mmHg for 20 min), the animals were
      randomized to two groups. At the start of laparoscopy, the test substance was
      applied intraperitoneally (group 1: controls, 1 ml 0.9% NaCl; group 2: 250 mg
      phosphoramidon in 1 ml 0.9% NaCl). Three weeks after the injection of tumor
      cells, the animals were autopsied and the tumor mass determined. RESULTS: In
      comparison with the control group (tumor weight 7.42 +/- 1.01 g), intraperitoneal
      tumor growth in the experimental group was significantly (p < 0.001) reduced by
      the application of phosphoramidon (tumor weight, 3.22 +/- 1.06 g). Phosphoramidon
      also significantly (p < 0.05) reduced tumor cell invasion through the matrix gel.
      CONCLUSION: The proteinase inhibitor phosphoramidon reduced tumor cell invasion
      in vitro and tumor cell growth in vivo in this laparoscopic rat model.

PMID- 11443464
TI  - A single-trocar technique for minimally-invasive surgery of the chest.
AB  - BACKGROUND: In thoracic surgery, the classic thoracoscope is used to perform
      simple maneuvers in the chest. We have devised a minimally invasive technique
      that requires only a single trocar. This technique is used in our department to
      diagnose and treat a wide range of thoracic pathologies. METHODS: Between October
      1998 and August 1999, 37 patients underwent surgery prospectively for a thoracic
      disease through a single trocar. There were 19 men and 18 women with a mean age
      of 60 years (range, 40-85). The trocar was flexible or soft and had a diameter of
      15-20 mm. A 2-cm skin incision was made in the planned intercostal space. The
      chest drain was always inserted under video control. RESULTS: The mean operative
      time was 53 +/- 5 min. One patient developed intraoperative bleeding that
      required intubation and a 5-cm mini-thoracotomy. In one patient with stage II
      empyema, it was necessary to insert another trocar. Chest tubes were removed
      after 77.7 +/- 7 h. Hospital stay was 4 +/- 1 days (range, 2-14). Histologic
      examination revealed malignant disease in 26 cases and benign disease in 11. Two
      patients (5.4%) developed wound infections. None of the patients had port site
      metastasis. There were no hospital deaths. CONCLUSION: Because of its simplicity,
      we recommend the use of this mini-invasive technique in place of the classic
      thoracoscope or video-mediastinoscope.

PMID- 11443465
TI  - Evaluation of the cost for laparoscopic-assisted Billroth I gastrectomy.
AB  - BACKGROUND: Despite the rapid spread of laparoscopic gastric surgery in Japan, no
      one has yet evaluated the costs for this new technique. The aim of this study was
      to analyze and compare the hospital charges for laparoscopic-assisted gastrectomy
      with those for conventional open gastrectomy. METHODS: The study included 48
      consecutive patients who underwent laparoscopic-assisted Billroth I gastrectomy
      and 43 who had a conventional open Billroth I gastrectomy for cure of early
      gastric cancer between May 1994 and April 2000. Hospital charges covered all
      costs incurred during the hospital stay; they were divided into charges for
      consultation, prescription, injection, nursing care, operating theater,
      laboratory, radiology, ward and meal, and others. RESULTS: The patients who
      underwent laparoscopic gastrectomy were similar to those who had open gastrectomy
      in terms of symptoms, concurrent illness, operation time, proximal resection
      margin, number of harvested lymph nodes, and stage of the disease. Hospital stay
      after laparoscopic gastrectomy was shorter than that after open gastrectomy (16.1
      vs 20.5 days, p < 0.01). Charges for nursing care, charges for ward and meal, and
      total hospital charges were less in the laparoscopic group than in the open group
      ( yen5800 vs yen8010, p < 0.01; yen461 x 10(3) vs yen512 x 10(3), p < 0.05;
      yen1336 x 10(3) vs yen1411 x 10(3), p = 0.072). When we compared laparoscopic
      gastrectomies performed during 1994-96 with those done during 1997-2000, we found
      a decrease in charges for ward and meal and total hospital charges ( yen498 x
      10(3) vs yen421 x 10(3), p < 0.01; yen1390 x 10(3) vs yen1277 x 103, p < 0.01).
      CONCLUSION: Laparoscopic-assisted Billroth I gastrectomy is less expensive than
      conventional open Billroth I gastrectomy because both the postoperative recovery
      period and the hospital stay are shorter. In patients who undergo gastrectomy,
      the additional costs of the disposable instruments can be fully offset by the
      lower charges for ward and meal and nursing care associated with laparoscopic
      gastrectomy.

PMID- 11443466
TI  - Effects of prolonged increased intra-abdominal pressure on gastrointestinal blood
      flow in pigs.
AB  - BACKGROUND: The aim of the study was to investigate the effects of prolonged
      intra-abdominal pressure on systemic hemodynamics and gastrointestinal blood
      circulation. METHODS: The intra-abdominal pressure in anesthetized pigs was
      elevated to 20 mmHg (7 animals), 30 mmHg (7 animals), and 40 mmHg (4 animals),
      respectively. These pressures were maintained for 3 h by intra-abdominal infusion
      of Ringer's solution. A control group of seven animals had normal intra-abdominal
      pressure (IAP). Transit time flowmetry and colored microspheres were used to
      measure blood flow. RESULTS: An IAP of 20 mmHg did not cause significant changes
      in systemic hemodynamics or tissue blood flow. An IAP of 30 mmHg caused reduced
      blood flow in the portal vein, gastric mucosa, small bowel mucosa, pancreas,
      spleen, and liver. Serum lactate increased in animals with an IAP of 30 mmHg, but
      microscopy did not disclose mucosal damage in the stomach or small bowel. An IAP
      of 40 mmHg was followed by severe circulatory changes. CONCLUSIONS: Prolonged IAP
      at 20 mmHg did not cause changes in general hemodynamics or gastrointestinal
      blood flow. Prolonged IAP at 30 mmHg caused reduced portal venous blood flow and
      reduced tissue flow in various abdominal organs, but no mucosal injury. A
      prolonged IAP of 40 mmHg represented a dangerous trauma to the animals.

PMID- 11443467
TI  - Technical considerations in laparoscopic liver surgery.
AB  - BACKGROUND: Laparoscopic solid organ surgery has gained growing acceptance, but
      this does not hold for laparoscopic surgery of the liver. Laparoscopic liver
      surgery mainly comprizes diagnostic procedures and treatment of liver cysts.
      However, we believe there is room for a laparoscopic approach to the liver in
      selected cases, with the benefits that may be expected from laparoscopic solid
      organ surgery. METHODS: Between 1993 and 2000, 10 patients with various lesions
      of the liver underwent laparoscopic surgery. Indications consisted of cystic
      disease (n = 2), hemangioma (n = 2), focal nodular hyperplasia (n = 2), liver
      abcess (n = 1), and liver metastasis (n = 3). Laparoscopic treatment varied from
      fenestration (n = 3) to wedge resections (n = 5), and formal left lateral
      hepatectomy (n = 2). RESULTS: The mean patient age was 54 years (range, 34-71
      years). The mean operative time, including laparoscopic ultrasonography, measured
      180 min (range, 80-240 min). Peroperative blood loss ranged from 200 to 450 ml.
      There was no mortality. In two patients, conversion to laparotomy was necessary.
      There were no postoperative complications. The mean hospital stay was 6 days
      (range, 4-11 days). CONCLUSION: Laparoscopic treatment should be considered in
      selected patients with benign and malignant lesions in the left lobe or frontal
      segments of the liver.

PMID- 11443468
TI  - The diagnostic dilemma of traumatic rupture of the diaphragm.
AB  - BACKGROUND: Traumatic rupture of diaphragm is caused by blunt or penetrating
      trauma. Early diagnosis is difficult, and complications such as visceral
      herniation may arise. A 10-year evaluation of all diagnostic procedures used in
      patients with surgically proved traumatic rupture of the diaphragm is presented.
      METHODS: A review of all patients with surgically proved diaphragmatic injury
      from 1988 to 1998 was conducted. All diagnostic methods were analyzed in terms of
      their ability to identify diaphragmatic rupture. RESULTS: During the study
      period, 31 patients with a mean age of 34 years were treated. Of these patients,
      20 sustained blunt trauma and 11 experienced penetrating trauma. The initial
      chest x-ray was diagnostic for 6 of the 31 patients, nonspecific for 15 of the
      patients, and normal for 10 of the patients. In no case was sonography
      diagnostic. Thoracoabdominal computed tomography (CT), performed in 22 of the
      patients, led to diagnosis for 5 patients and unspecific findings for 17
      patients. Statistical analyses showed no significant difference between initial
      chest x-ray and thoracoabdominal CT. No significant difference between blunt or
      penetrating trauma or between left-side and right-side ruptures could be
      recognized with any diagnostic tool. CONCLUSIONS: All the diagnostic methods
      investigated in this study showed unsatisfying results, and traumatic rupture of
      the diaphragm seems to remain a diagnostic dilemma. Endoscopic techniques not
      tested in this study and discussed controversially may offer a good chance for
      early diagnosis and repair of the injured diaphragm.

PMID- 11443469
TI  - Morphology of the murine peritoneum after pneumoperitoneum vs laparotomy.
AB  - BACKGROUND: Although there have been studies of the effects of pneumoperitoneum
      on the peritoneal cavity, we still do not know whether the morphologic changes to
      the peritoneum are different for pneumoperitoneum vs laparotomy. Using scanning
      electron microscopy, we examined the murine peritoneum after pneumoperitoneum vs
      laparotomy and compared the changes. METHODS: Forty-five mice were anesthetized
      with diethyl ether and divided into seven groups. Pneumoperitoneum was
      established at 5 mmHg for 30 min with carbon dioxide (CO(2)) (n = 9), helium (n =
      9), and air (n = 9). One group underwent laparotomy for 30 min (n = 9), and a
      control group underwent anesthesia only (n = 3). CO(2) pneumoperitoneum was
      further established at 10 mmHg for 30 min (n = 3) and at 5 mmHg for 60 min (n =
      3). After the procedures, the peritoneum was resected from the mesenterium of the
      small intestine in each animal and examined by scanning electron microscope for
      morphologic changes of the mesothelial cells. RESULTS: Bulging up of the
      mesothelial cells was evident immediately after pneumoperitoneum, whereas
      detachment of the mesothelial cells was present immediately after laparotomy.
      Bulging up of the mesothelial cells was reduced at 24 h after CO(2)
      pneumoperitoneum and fully resolved at 72 h in all pneumoperitoneum groups,
      whereas the mesothelial cells remained detached at 72 h in the laparotomy group.
      Intercellular clefts were found immediately after helium pneumoperitoneum and
      were present at 24 h and 72 h after helium pneumoperitoneum, but they were not
      seen after air pneumoperitoneum and were only evident after CO(2)
      pneumoperitoneum at 10 mmHg. Depression of the mesothelial cell surface was
      observed when pneumoperitoneum lasted 60 min. CONCLUSION: Morphologic peritoneal
      alterations after pneumoperitoneum differed from those after laparotomy and were
      influenced by the type of gas, amount of pressure, and duration of insufflation.
      These peritoneal changes after pneumoperitoneum may be associated with a specific
      intraperitoneal tumor spread after laparoscopic cancer surgery.

PMID- 11443470
TI  - Lipid peroxidation and the use of emulsified propofol in laparoscopic surgery.
AB  - BACKGROUND: Free radical-induced lipid peroxidation associated with a decrease of
      antioxidant capacity in plasma is observed after the deflation of the
      pneumoperitoneum in laparoscopic surgery. In this study, we evaluated the effect
      of the continuous administration of lipid peroxidation derivatives on emulsified
      propofol. METHODS: Two groups of 20 patients each who underwent laparoscopic
      surgery were studied prospectively. Maintenance of anesthesia was achieved with
      66% nitrous oxide and either isoflurane or continuous propofol administration.
      The level of thiobarbituric acid-reactive substances (TBARS) in the plasma was
      determined as a measure of free radicals before and after surgery. RESULTS: Ten
      patients in the propofol group had reduced TBARS, as compared to only one in the
      isoflurane group (p = 0.003). There was a statistically significant difference in
      age between the patients with reduced TBARS and those without reduced TBARS (p =
      0.009) in the propofol group. CONCLUSIONS: Anesthesia with continuous propofol
      infusion in laparoscopic surgery has a significant scavenging action on the
      formation of free radicals and exerts its greatest antioxidant effect in patients
      >/=48 years of age.

PMID- 11443471
TI  - Increased expression of P-cadherin mRNA in the mouse peritoneum after carbon
      dioxide insufflation.
AB  - BACKGROUND: Although systemic responses to carbon dioxide (CO(2))
      pneumoperitoneum have been studied, there have been few reports of local
      responses within the peritoneum. We investigated the expression of mRNA for
      adhesion molecules involved in cell-cell interactions, including ICAM-1, VCAM-1,
      CD44, E-cadherin, P-cadherin, and N-cadherin, after the induction of a CO(2)
      pneumoperitoneum in mice. METHODS: Mice were treated with CO(2) pneumoperitoneum
      (4-6 mmHg for 30 min) and then killed after 24 h, 48 h, and 72 h. The peritoneum
      of the abdominal wall was resected, and total RNA was extracted by the acid
      guanidinium thiocyanate-phenol-chloroform extraction procedure, cDNA were
      synthesized by reverse transcription. Expression of the mRNA for each gene was
      normalized to that of b-actin for semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: The expression of P-cadherin mRNA
      was significantly increased at 48 h (p = 0.007) and returned to the control level
      by 72 h after CO(2) pneumoperitoneum. The expression of CD44 increased gradually,
      reaching a peak at 48 h and returning to the control value by 72 h after CO(2)
      pneumoperitoneum. Expression of ICAM-1 mRNA was not changed significantly after
      the application of CO(2). CONCLUSION: The expression of P-cadherin mRNA in the
      peritoneum can be induced to repair injuries to mesothelial cells caused by CO(2)
      pneumoperitoneum.

PMID- 11443472
TI  - Preincisional intravenous low-dose ketamine and local infiltration with
      ropivacaine reduces postoperative pain after laparoscopic cholecystectomy.
AB  - BACKGROUND: The preincisional use of ketamine combined with local tissue
      infiltration with Ropivacaine may reduce noxious input during surgery. The goal
      of this study was to examine whether this combination improves postoperative pain
      control after laparoscopic cholecystectomy. METHODS: A total of 55 patients were
      randomly assigned to one of three groups. Group 1 received placebos
      preincisional. Group 2 received preincisional saline IV and local infiltration
      with 20 ml ropivacaine (10 mg/ml). Group 3 received preincisional ketamine 1
      mg/kg IV and local infiltration with 20 ml ropivacaine (10 mg/ml). Postoperative
      pain was rated at 0, 3, 6, 12, 24, and 48 h postoperatively by visual analogue
      scale scores (VAS). Cumulative analgesic consumption and time until first
      analgesic medication request were recorded. RESULTS: Group 3 experienced
      significantly (p < 0.05) less pain than group 2 at 6 h and 12 h postoperatively.
      Groups 2 and 3 did not differ significantly by VAS at 0 h, 3 h, 24 h, and 48 h.
      Group 1 had significantly higher VAS scores than groups 2 and 3 at 0 h, 3 h, 6 h,
      12 h, and 24 h postoperatively. The consumption of analgesics was significantly
      higher in group 1 than in groups 2 and 3. Although the consumption of analgesics
      was higher in group 3 than in group 2, this difference did not reach statistical
      significance. The time to first request for analgesics was significantly longer
      in groups 2 and 3 than in group 1, with no statistical difference between groups
      2 and 3. CONCLUSION: Preincisional treatment with low-dose IV ketamine and local
      infiltration with ropivacaine 1% reduces postoperative pain after laparoscopic
      cholecystectomy.

PMID- 11443473
TI  - The umbilicus in laparoscopic surgery.
AB  - BACKGROUND: This study examines the factors related to infection and incisional
      herniation after laparoscopy at the umbilicus, as compared with those at remote
      sites. METHODS: From a prospective database of 561 cholecystectomies, 190
      inguinal hernia repairs, 71 Nissen fundoplications, and 51 ventral hernia
      repairs, 873 consecutive Hasson cannula sites, 748 umbilicus sites, and 125
      remote sites were analyzed. RESULTS: The wound infection rate was found to be 6%:
      7% at the umbilicus (9% after cholecystectomy and 2% after other operations [p <
      0.05]) and 0% at remote sites (p < 0.05). Excluding cholecystectomy, the
      umbilical infection rate was 2%, similar to that at remote sites. The
      postoperative ventral hernia rate was at 0.8%, the same at the umbilicus as
      elsewhere. The rate was similar for gallbladder and nongallbladder operations and
      correlated with the postoperative wound infection rate, but not with the
      preexisting fascial defect rate. CONCLUSIONS: Wound infection at the umbilicus is
      similar to that at other sites, except after cholecystectomy. Postoperative
      ventral hernia at the umbilicus is similar to that at other sites and not related
      to preexisting fascial defects.

PMID- 11443474
TI  - Practical recommendations for the prediction and management of common bile duct
      stones in patients with gallstones.
AB  - BACKGROUND: Approximately 10% of patients with symptomatic gallstones may have
      associated common bile duct stones (CBDS). However, the predictive value of
      noninvasive tests as well as the preoperative diagnosis and management of CBDS
      have not been well defined. The aim of this study was to define an accurate and
      simple model for the prediction and management of CBDS. METHODS: A prospective
      database containing 986 cholecystectomies performed from 1994 through 1999 was
      evaluated. Univariate analysis using the Pearson chi-square test was performed to
      determine the factors significantly related to the presence of CBDS. Then
      logistic regression analysis was performed for multivariate analysis to discover
      independent predictors. RESULTS: Of the 986 patients in this study, 48 (5%) had
      CBDS. Of the 48 patients with choledocholithiasis, 22 (46%) were men and 26 (54%)
      were women. The mean age was 55.3 years (range, 16-87 years). As a result of
      multivariate analysis, abdominal ultrasonographic findings suggestive of CBDS
      (common bile duct diameter exceeding 8 mm or visible stones), total bilirubin,
      and gamma glutamyl transpeptidase levels above normal were the independent
      predictors of CBDS in patients age 70 or younger. On the other hand, an elevated
      bilirubin level was found to be the single independent factor related to CBDS in
      the elderly. CONCLUSIONS: For patients with gallstones, suggestive
      ultrasonographic findings in those younger than 71 years and elevated direct or
      total bilirubin level in those older than 70 years are the most valuable and
      practical predictors of CBDS, and thus are the proper indications for
      preoperative endoscopic retrograde cholangiography.

PMID- 11443475
TI  - Risk factors resulting in conversion of laparoscopic cholecystectomy to open
      surgery.
AB  - BACKGROUND: Laparoscopic cholecystectomy has become the standard treatment for
      symptomatic gallbladder diseases. However, there still is a substantial
      proportion of patients in whom laparoscopic cholecystectomy cannot be
      successfully performed, and for whom conversion to open surgery is required.
      METHODS: In this study, 1,000 laparoscopic cholecystectomies performed at Ankara
      Numune Hospital, Fourth Department of Surgery, from March 1992 to July 1999 were
      prospectively analyzed. The patients studied included 804 women (80.4%) and 196
      men (19.6%) with a mean age of 43.8 years (range, 30-80 years). From the data
      collected, only factors available to the surgeon preoperatively were considered
      for analysis. These factors included age, gender, history of acute cholecystitis,
      jaundice or pancreatitis, previous abdominal surgery, obesity and concomitant
      disease, white blood cell (WBC) count, preoperative liver function tests,
      ultrasound findings of the gallbladder, preoperative endoscopic retrograde
      cholangiopancreatography (ERCP), and suspicion of common bile duct stones. Also
      we analyzed the case numbers as a measure of institutional experience. RESULTS:
      Of the 1,000 patients in whom laparoscopic cholecystectomy was attempted, 48
      (4.8%) required conversion to open surgery. The most common reason for conversion
      was inability to define anatomy in patients with inflamed contracted gallbladder
      (n = 34). Significantly independent predictive factors for conversion were male
      gender, previous abdominal surgery, acute cholecystitis, thickened gallbladder
      wall on preoperative ultrasonography, and suspicion of common bile duct stones.
      CONCLUSIONS: An appreciation for the aforementioned predictors of conversion will
      allow appropriate planning by the patient, the institution, and the surgeon.

PMID- 11443476
TI  - Laparoscopic colorectal resection in octogenarians.
AB  - BACKGROUND: The number and proportion of patients aged ?80 years are increasing.
      These patients often require surgical care and suffer subsequent high rates of
      morbidity and mortality. However, the surgical outcomes of laparoscopic
      colorectal resection in octogenarians are not well documented. METHODS:
      Octogenarians were identified from a large prospective database comprising 507
      consecutive laparoscopic colorectal resections performed between 1991 and 1999 in
      a university setting. Preoperative comorbidity and surgical outcomes were
      analyzed. RESULTS: Sixty-two patients (30 men, 32 women) aged ?80 years were
      identified. Their mean age and weight were 85 years and 63 kg, respectively.
      Seven patients (11%) were converted to an open procedure. Four (6%)
      intraoperative complications occurred in four patients (one colon perforation,
      one small bowel perforation, one burned gallbladder serosa, and one missed
      lesion), necessitating two conversions. Twenty -four postoperative complications
      occurred in 19 patients (31%) (six ileus [10%], five wound infections [8%], five
      cardiac problems [8%], two urinary retentions [3%], two hemorrhages [3%], one
      abscess [2%], one pneumonia [2%], and two other [3%]). Intraoperative
      complications did not increase postoperative morbidity. Three patients (5%) died
      within 30 days of surgery. When the procedure was completed laparoscopically, the
      overall median postoperative hospital stay was 10.0 days; occurrence of a
      postoperative complication increased the median length of stay to 15.0 days.
      CONCLUSIONS: These results are superior to published historical controls
      involving open colorectal resection in octogenarians. Overall mortality, lung,
      and urinary tract complications were decreased, and there were no reoperations
      for small bowel obstruction. Laparoscopic colorectal resection is technically
      feasible and can be done safely in elderly patients. Results require
      randomization against those for open surgery to elucida te the real advantages of
      this technique.

PMID- 11443477
TI  - The effect of laparoscopic instrument working angle on surgeons' upper extremity
      workload.
AB  - BACKGROUND: Laparoscopic surgery may be kinder to the patient, but it is more
      demanding on the surgeon. Fixed trocar positions often require the surgeon to
      work with instruments at awkward angles to their body. We studied the effect of
      horizontal and vertical laparoscopic instrument working angle on the surgeon's
      thumb, forearm, and shoulder muscle work. METHODS: Electronyographic (EMG)
      signals were collected from the thenar compartment (TH), flexor digitorum
      superficialis (FDS), and deltoid (DEL) muscles of the dominant arm of eighth
      surgeons while they were closing a standard pistol-grip disposable laparoscopic
      grasper against a fixed resistance of 3 N. With the aid of a special testing
      bench, the instruments' position was randomly changed among 15 degrees, 45
      degrees, and 75 degrees of horizontal angulation relative to the surgeons'
      sagital plane, and 15 degrees, 45 degrees, and 75 degrees degrees of vertical
      angulation relative to a horizontal plane. EMG signals were rectified and
      smoothed using analogue circuitry and digitally sampled at l0 Hz using a National
      Instruments DAQCard-700 connected to a Macintosh PowerBook 5300c running LabVIEW
      software. Statistical analysis was carried out by analysis of variance (ANOVA).
      RESULTS: The effects of vertical and horizontal working angles on the muscle
      effort were as follows: TH (horizontal, N.S.; vertical, N.S.), FDS (horizontal, p
      45 degrees to the surgeon's sagital plane significantly increases the workload of
      the flexor digitorium superficialis and deltoid muscles. The deltoid muscle is
      also adversely affected by vertical angulation of the instrument. The instrument
      working angle has no effect on the thenar muscles. Whenever possible,
      laparoscopic surgeons should strive to place their instruments and trocars so as
      to minimize extreme horizontal or vertical displacement of their hands away from
      a resting position of comfort.

PMID- 11443478
TI  - Laparoscopic radiofrequency ablation of unresectable hepatic malignancies. A
      phase 2 trial.
AB  - BACKGROUND: Radiofrequency ablation (RFA) of hepatic malignancies has been
      performed successfully via a percutaneous route or at laparotomy. We analyzed the
      efficacy and utility of laparoscopic intraoperative ultrasound and RFA in
      patients with unresectable hepatic malignancies. METHODS: Between November 1997
      and November 1999, 27 patients with unresectable hepatic malignancies and no
      evidence of extrahepatic disease were entered in a phase 2 trial of laparoscopic
      intraoperative ultrasound and RFA. Real-time ultrasonography was used to guide
      RFA, and lesions were ablated at a temperature of 100 degrees C for 10 min.
      Overlapping ablations were performed for larger lesions. RESULTS: Additional
      tumors were identified in 10 (37%) of the 27 study patients by laparoscopy and
      laparoscopic intraoperative ultrasound despite extensive preoperative imaging.
      Radiofrequency ablation of 85 hepatic tumors yielded no mortality and only one
      case of postoperative bleeding. During a mean follow-up period of 14 months, four
      tumors (4.7%) locally recurred. Of the 27 patients, 11 (41%) remain free of
      disease at this writing; (22%) are alive with disease; and 10 (37%) have died
      with disease. CONCLUSION: Laparoscopic RFA and intraoperative ultrasound
      constitute a safe and accurate method for ablation of unresectable hepatic
      tumors.

PMID- 11443479
TI  - Use of laparoscopy in the management of mesenteric venous thrombosis.
AB  - Mesenteric vein thrombosis is a relatively rare cause of intestinal ischemia. We
      present a case of idiopathic superior mesenteric and portal vein thrombosis,
      which was not associated with any infarcted bowel. The patient was treated
      successfully with anticoagulation using low-molecular weight heparin and
      warfarin, and did not require bowel resection. This case highlights the value of
      diagnostic laparoscopy for assessing intestinal viability in this situation,
      showing how it avoids the morbidity and complications associated with a formal
      laparotomy.

PMID- 11443480
TI  - Nodular amyloidosis: case report and literature review.
AB  - BACKGROUND: Amyloidosis refers to a group of depositional diseases that are
      classified into two main types: systemic and localized. Large nodules of
      localized cutaneous amyloidosis of the nasal ala and surrounding skin are rare
      and the treatment is often unsatisfactory. OBJECTIVE: We report a case of rapidly
      enlarging, localized, nodular cutaneous amyloidosis of the nose and the
      surrounding skin with a brief review of the current literature regarding
      treatment of this rare disease. CONCLUSION: Nodular amyloidosis can be treated
      successfully with cold steel excision in combination with carbon dioxide laser.
      Close followup of these patients is warranted, as nodular amyloidosis may be the
      precursor to systemic amyloidosis.

PMID- 11443481
TI  - Measurement properties of Skindex-16: a brief quality-of-life measure for
      patients with skin diseases.
AB  - BACKGROUND: An accurate, sensitive, but brief quality-of-life outcomes measure is
      needed for studies of dermatologic care. OBJECTIVE: To construct a single-page
      version of Skindex (a dermatologic quality-of-life instrument) that would have
      two new features compared with the current 29-item version: (1) fewer items to
      which a majority of patients choose the same response, and (2) measurement of
      bother rather than frequency of patient experiences. METHODS: Random samples of
      patients waiting for dermatology appointments in clinics of Veterans Affairs
      hospitals and in private dermatology practices completed questionnaires; 692
      patients responded to the parent instrument and 541 additional patients responded
      to the brief version. Reproducibility, internal consistency reliability,
      validity, and responsiveness of the brief version of Skindex were determined.
      RESULTS: For 16 items of the current 29-item version (55%), more than 50% of
      patients responded "Never." After an explicit process of item analysis and
      elimination, a single-page 16-item version was composed that asks patients about
      bother from their experiences; responses are reported as three scales, Symptoms,
      Emotions, and Functioning. For 6 items of the 16-item version (38%), more than
      50% of patients responded "Never." Scale scores were reproducible after 72 hours
      (r = 0.88-0.90) and were internally reliable (Cronbach's alpha = 0.86-0.93). The
      instrument demonstrated both content and construct validity: Most patients'
      responses to an open-ended question about their skin disease was addressed by the
      items; patients with inflammatory dermatoses had higher scores than those with
      isolated lesions; and in an exploratory principal axes factor analysis with an
      oblique rotation, 74% of the common variance was explained by three factors that
      correlated with the a priori scales. Mean scale scores stayed the same or changed
      in the expected direction in patients who reported that their skin was the same
      or had improved. CONCLUSION: This brief single-page version of Skindex accurately
      and sensitively measures how much patients are bothered by their skin conditions.

PMID- 11443482
TI  - Teledermatology in New Zealand.
AB  - BACKGROUND: Teledermatology is the delivery of specialist dermatological services
      at a distance. It has become possible because of technological advances in
      digital imaging and telecommunications. Consultations may be "interactive" using
      video-conferencing equipment or "store-and-forward" using prerecorded text and
      images. The best method to deliver teledermatology services is unknown.
      OBJECTIVE: Studies were designed to determine (a) if it was possible to diagnose
      and manage skin diseases using video-conferencing equipment, (b) if
      teledermatology was acceptable to patients and medical practitioners, and (c)
      whether it offered any economic advantages. We have also compared interactive and
      store-and-forward techniques. METHOD: The trials were conducted in collaboration
      with the Institute of Telemedicine & Telecare, Queen's University, Belfast, as
      part of the UK Teledermatology Trials. RESULTS: The trials have involved more
      than 300 teledermatology consultations. Having established that a diagnosis can
      be made in more than two-thirds of the cases, the majority of video consultations
      have resulted in satisfactory management, with only small numbers of patients
      requiring face-to-face review. Teledermatology is generally popular with patients
      and can save them considerable time and money. Routine clinics continue in three
      centers. We have found that effective store-and-forward teledermatology requires
      very good images and comprehensive historical referral data.

PMID- 11443483
TI  - The morbid anatomy of the dermatologic genome: an update for the third
      millennium.
AB  - BACKGROUND: Much progress has been made in recent years in the identification of
      genes underlying many hereditary skin diseases. OBJECTIVE: To provide an update
      on the status of the identification of genes involved in hereditary skin
      disorders and to compare the current standing with that in the last decade.
      METHODS: A review of the literature is presented here in a series of lists
      describing the chromosomal location, specific gene, clinical relevance, and
      availability of molecular-based genetic tests for each genodermatosis. RESULTS:
      Progress has been made in identifying the genes underlying many disorders of
      cornification, genodermatoses with malignant potential, bullous disorders,
      pigmentary disorders, disorders affecting the epidermal appendages and the
      dermis, and other miscellaneous genodermatoses. CONCLUSION: The great progress
      made toward the completion of the human gene sequence and the continued efforts
      of many clinical and molecular scientists to identify disease genes will make
      diagnosis of hereditary dermatological disorders more precise and allow accurate
      family counseling as well as possibly leading to more targeted therapies during
      this millennium.

PMID- 11443484
TI  - Postirradiation multiple minute digitate porokeratosis.
AB  - BACKGROUND: Development of multiple minute digitate hyperkeratoses (MMDH) after
      irradiation has been reported previously. The keratotic lesions in these cases
      were confined within the irradiation field, and histopathological examination
      disclosed a focal column of parakeratosis (cornoid lamella) arising from an
      epidermis devoid of granular layer. OBJECTIVE: We describe a 78-year-old woman
      who developed multiple, discrete, tiny, filiform, keratotic papules on the
      anterior aspect of the right chest wall, 13 months after postmastectomy cobalt
      irradiation therapy for mammary infiltrating ductal carcinoma. CONCLUSION:
      Postirradiation MMDH represents a peculiar radiation-induced disorder that we
      believe should be distinguished from other cases of MMDH and included within the
      spectrum of porokeratosis.

PMID- 11443485
TI  - Alopecia areata universalis in an infant.
AB  - BACKGROUND: Alopecia areata (AA) is common during childhood and rarely reported
      in infants. The four reported cases of AA in infants all exhibited circumscribed
      patches of alopecia that appeared at birth or shortly thereafter. OBJECTIVE: We
      report a case of alopecia areata universalis that developed after birth along
      with fingernail changes of shortening (onychomadesis) and onycholysis. Scalp
      biopsy at 2 years of age revealed rare, intermediate, terminal follicles in
      catagen associated with sparse peribulbar lymphocytic infiltrates. RESULTS: This
      constellation of clinicopathologic features was interpreted as AA. We discuss the
      differential diagnosis of generalized alopecia in healthy infants, in particular,
      Clouston's syndrome, a hair-nail (hidrotic) ectodermal dysplasia found in this
      region. Genetic testing for linked polymorphisms to the Clouston gene locus were
      negative in this child and his parents. CONCLUSIONS: Alopecia areata should be
      included in the differential diagnosis of generalized alopecia presenting at or
      shortly after birth. For purposes of genetic counseling and prognosis, it is
      crucial that a correct diagnosis be made.

PMID- 11443486
TI  - Disseminated scleroderma of a Japanese patient successfully treated with bath
      PUVA photochemotherapy.
AB  - BACKGROUND: Localized scleroderma is known to be resistant to therapies.
      Recently, it has been reported that bath PUVA photochemotherapy is effective for
      treating this dermatosis. OBJECTIVES: Although according in earlier reports
      mainly white populations have been treated successfully with bath PUVA therapy,
      there is little knowledge of whether it is effective in treating colored
      populations. We treated a 64-year-old Japanese woman suffering from disseminated
      scleroderma with bath PUVA photochemotherapy to see its effects. CONCLUSION:
      Although rather high cumulative UVA doses were required for this patient compared
      with those needed in earlier reports, no adverse effects were observed. The
      lesions were markedly improved, suggesting that this therapeutic modality is well
      tolerated and useful for colored patients such as the Japanese. Furthermore, it
      turns out that the thermographical assessment is useful to estimate clinical
      improvement of this sclerosing skin disorder.

PMID- 11443487
TI  - The role of psychological stress in skin disease.
AB  - BACKGROUND: Numerous case reports and studies have suggested that psychological
      stress may have a role in the onset or exacerbation of a variety of skin
      diseases. OBJECTIVE: We review the literature pertaining to the role of
      psychological stress in the exacerbation of psoriasis, urticaria, eczematous
      dermatitis, herpesvirus infections, and other skin diseases; discuss potential
      mechanisms of stress-induced skin disease; and review studies and case reports of
      psychotherapeutic interventions that have been found helpful in the therapy of
      skin diseases. CONCLUSIONS: There is evidence linking psychological stress to
      exacerbation of certain skin diseases. Both the clinical and the basic science
      evidence, however, can be hard to interpret in light of the difficulty of
      defining and quantifying psychological stress as well as the questions regarding
      the etiologic significance of neuroimmunologic findings in skin diseases.

PMID- 11443488
TI  - Prediction of energy expenditure in a whole body indirect calorimeter at both low
      and high levels of physical activity.
AB  - OBJECTIVES: In studies that involve the use of a room calorimeter, 24 h energy
      intake is often larger than 24 h energy expenditure (24 h EE) because of a
      decrease in activity energy expenditure due to the confined space. This positive
      energy balance can have large consequences for the interpretation of substrate
      balances. The objective of this study was to develop a method for predicting an
      individual's 24 h EE in a room calorimeter at both low (1.4xRMR) and high
      (1.8xRMR) levels of physical activity. METHODS: Two methods are presented that
      predict an individual's 24 h EE in a metabolic chamber. The first method was
      based on three components: (1) a 30 min measurement of resting metabolic rate
      (RMR) using a ventilated hood system; (2) measurement of exercise energy
      expenditure during 10 min of treadmill walking; and (3) estimation of free-living
      energy expenditure using a tri-axial motion sensor. Using these measurements we
      calculated the amount of treadmill time needed for each individual in order to
      obtain a total 24 h EE at either a low (1.4xRMR) or a high (1.8xRMR) level of
      physical activity. We also developed a method to predict total 24 h EE during the
      chamber stay by using the energy expenditure values for the different levels of
      activity as measured during the hours already spent in the chamber. This would
      provide us with a tool to adjust the exercise time and/or energy intake during
      the chamber stay. RESULTS: Method 1: there was no significant difference in
      expected and measured 24 h EE under either low (9.35+/-0.56 vs 9.51+/-0.47
      MJ/day; measured vs predicted) or high activity conditions (13.41+/-0.74 vs
      13.97+/-0.78 MJ/day; measured vs predicted). Method 2: the developed algorithm
      predicted 24 h EE for 97.6+/-4.0% of the final value at 3 h into the test day,
      and for 98.6+/-3.7% at 7 h into the test day. CONCLUSION: Both methods provide
      accurate prediction of energy expenditure in a room calorimeter at both high and
      low levels of physical activity. It equally shows that it is possible to
      accurately predict total 24 h EE from energy expenditure values obtained at 3 and
      7 h into the study.

PMID- 11443489
TI  - Physical inactivity as a determinant of the physical activity level in the
      elderly.
AB  - OBJECTIVE: To assess the relationship between the mean physical activity level
      (PAL) and the time spent on activities of three different intensity levels in an
      elderly population. Data was compared with previously obtained data from a group
      of younger adults. SUBJECTS: Fourteen elderly women and 14 elderly men (61+/-4 y;
      27+/-5 kg/m(2); 33+/-7% body fat), and 14 young women and 16 young men (27+/-5 y,
      24+/-2 kg/m(2)). MEASUREMENTS: PAL was determined as average daily metabolic rate
      (ADMR) combined with a measurement of basal metabolic rate (BMR): PAL=ADMR/BMR.
      ADMR was measured with the doubly labeled water method. BMR was measured with a
      ventilated hood system. Time spent on activity and activity intensity was
      measured by using a tri-axial accelerometer (7x2x0.8 cm, 30 g) over a 2 week
      interval. RESULTS: Mean PAL was 1.65+/-0.14. PAL was inversely related to the
      percentage of time spent on low-intensity activity (lying, sitting and standing),
      r= -0.43; P<0.05. Older subjects spent significantly more time at these
      activities than 20 to 35-y-old subjects (82+/-7% vs 65+/-7%; P<0.0001). A
      significant relation was not observed between PAL and the percentage of time
      spent on moderate (walking) or high (household activities, exercise and sports)
      intensity activity, or activity monitoring time (14.4+/-1.2 h/day). CONCLUSION:
      In the elderly, spending relatively more time on low-intensity activities affects
      the mean PAL negatively. To obtain a higher PAL does not necessarily imply high
      intensity activities like sports.

PMID- 11443490
TI  - Leisure-time physical activity and regular walking or cycling to work are
      associated with adiposity and 5 y weight gain in middle-aged men: the PRIME
      Study.
AB  - OBJECTIVE: To examine the influence of physical activity on body mass index
      (BMI), waist circumference (W) and body mass changes (DeltaBMI) in middle-aged
      men, with special regard to moderate-intensity activities. DESIGN: Longitudinal
      study of adults who participated in the PRIME Study. SUBJECTS: A cohort of 8865
      men aged 50-59 y, free of coronary heart disease. MEASUREMENTS: BMI and W at
      baseline, body mass changes over a 5 y period. Detailed baseline assessment of
      net energy expenditure due to physical activity (PAE) in the preceding year,
      according to category of activity, by means of the MOSPA Questionnaire. PAE was
      expressed in weekly metabolic equivalent scores (MET h/week). RESULTS: After
      adjustment for confounders, the multiple regression analyses indicated that BMI,
      W and DeltaBMI were inversely associated with PAE spent in getting to work (P<10(
      5), <10(-5) and 0.04, respectively) and practice of high-intensity (>or=6 MET)
      recreational activities (<0.01, <10(-5) and <0.01). Men who regularly spent more
      than 10 MET h/week in walking or cycling to work had a mean BMI, W and DeltaBMI
      respectively 0.3 kg/m(2), 1 cm and 0.06 kg/m(2) lower than those who did not
      expend energy in getting to work. In the subgroup of subjects who did not perform
      high-intensity activities, the level of recreational PAE was inversely associated
      with BMI and W but not with subsequent weight-gain. CONCLUSION: These findings
      indicate that, in middle-aged men, physical activities of moderate-intensity,
      which are probably easier to promote than more vigorous activities and, in
      particular, a more current daily activity, walking or cycling to work, may have a
      favourable effect on body fat markers and body mass gain.

PMID- 11443491
TI  - Do African-American and Caucasian overweight women differ in oxygen consumption
      during fixed periods of exercise?
AB  - OBJECTIVE: To examine whether there are ethnic differences in oxygen consumption
      during fixed periods of exercise. DESIGN: Cross-sectional. SUBJECTS: Twenty-seven
      African-American and 120 Caucasian overweight adult women (body mass index=32.8+/
      4.1 kg/m(2), age=36.7+/-5.6 y) prior to initiating a weight loss program.
      MEASUREMENTS: Measurement of oxygen consumption occurred during four stages of a
      graded exercise test, with body composition assessed by dual-energy X-ray
      absorptiometry. RESULTS: There were no significant differences between overweight
      African-American and Caucasian women for absolute oxygen consumption or oxygen
      consumption adjusted for either body weight or fat-free mass across four levels
      of a submaximal graded exercise test. CONCLUSION: The results from this study
      suggest that African-American and Caucasian women do not differ in energy
      expenditure during fixed workloads of exercise, suggesting that this may not
      contribute to differences in energy balance and body weight regulation between
      women in these two ethnic groups.

PMID- 11443492
TI  - Twenty-four hour energy expenditure and substrate oxidation before and after 6
      months' ad libitum intake of a diet rich in simple or complex carbohydrates or a
      habitual diet.
AB  - OBJECTIVE: To investigate 24 h energy expenditure (24 h EE) and substrate
      oxidations in overweight and obese subjects before and after 6 months' ad libitum
      intake of a low-fat, high-simple carbohydrate diet (SCHO), a low-fat, high
      complex carbohydrate diet (CCHO), or a habitual control diet (CD). SUBJECTS:
      Twenty-four healthy overweight and obese subjects (11 males and 13 females; body
      mass index 30.7+/-0.6 kg/m(2); age 42.2+/-1.8 y). MEASUREMENTS: Twenty-four hour
      EE, substrate oxidation rates and spontaneous physical activity (SPA) measured in
      a respiration chamber, and food intake. RESULTS: After the intervention no
      differences were seen in 24 h EE, postprandial thermogenesis, basal metabolic
      rate or SPA. Carbohydrate oxidation, adjusted for energy balance, increased on
      both carbohydrate-rich diets (SCHO 13.0%, CCHO 11.5%) and decreased on the CD
      diet (6.5%); however, the changes were not significantly different between diets.
      The opposite pattern was seen for fat oxidation, which increased by 2.9% on the
      CD diet and decreased by 17.1 and 25.6% on the SCHO and CCHO, respectively. The
      changes only differed between the CD and CCHO diet (P=0.03). CONCLUSION: Six
      months' ad libitum intake of a diet rich in simple or complex carbohydrates or a
      habitual diet induced a shift in the oxidation pattern to closely reflect the
      diet composition in overweight and obese subjects. No differences between diets
      were seen in 24 h EE.

PMID- 11443493
TI  - Low physical performance in obese adolescent boys with metabolic syndrome.
AB  - OBJECTIVE: To assess cardiorespiratory exercise function in obese children with
      and without metabolic syndrome (MS). DESIGN: Comparing three groups of subjects
      with different cardiovascular risk profiles. SUBJECTS: Twenty-two MS (body weight
      (mean+/-s.d.) 97.3+/-15.3 kg; age (mean+/-s.d.) 14.2+/-1.9 y), 17 obese (82.6+/
      15.7 kg; 14.2+/-2.6 y) and 29 normal weight control (64.3+/-8.5 kg; 15.3+/-1.0 y)
      boys. MEASUREMENTS: Exercise duration (ED), resting heart rate (HR(0)), peak
      heart rate (HR(peak)), physical working capacity at 170 beat/min (PWC-170), peak
      oxygen consumption (VO(2peak)) and the lactic acidosis threshold (LAT) were
      determined on treadmill, using a continuous ramp protocol. RESULTS: ED (MS
      (mean+/-s.d.); 655+/-86 s; obese 703+/-64 s; control 750+/-0 s) in absolute value
      and PWC-170 normalised for body weight (139+/-40 w; 177+/-40 w; 211+/-40 w) were
      significantly shorter and lower in the MS group, as compared to obese and control
      groups (P<0.05). VO(2peak) (2.2+/-0.4 l/min; 2.4+/-0.5 l/min; 2.9+/-0.4 l/min)
      and LAT (1.3+/-0.4 l/min; 1.5+/-0.4 l/ min; 1.8+/-0.4 l/min) normalised for body
      weight, were significantly shorter and lower in the MS group, as compared to
      control group (P<0.05). HR(0) was significantly higher (P<0.05) in MS group than
      in obese and control groups (88+/-12 bpm; obese 78+/-10 bpm; 73+/-10 bpm).
      CONCLUSION: Cardiorespiratory exercise performance capacity in MS boys are
      reduced. It still remains to be elucidated whether the metabolic alterations or
      the decreased physical activity is responsible for the observed reduction in
      cardiorespiratory performance.

PMID- 11443494
TI  - Food and activity preferences in children of lean and obese parents.
AB  - BACKGROUND: Children of obese parents have a substantially higher risk of adult
      obesity than children of lean parents. Adoption and twin studies have shown that
      this risk is largely genetic but the proximal mechanisms of the genetic risk are
      not known. Comparisons of energy intake or expenditure in children of obese and
      lean parents have produced mixed, but generally negative results. An alternative
      hypothesis is that the early expression of obesity risk is through food and
      activity preferences, which provides a basis for later weight gain. The aim of
      this study was therefore to compare food and activity preferences in a large
      sample of young children from obese and lean families using parental obesity as a
      marker of the obesity-risk phenotype. Because the children from the families with
      obese parents were not yet overweight, differences observed in the two types of
      families are more likely to be causes than effects of obesity. METHODS: A total
      of 428 children aged 4-5 y, whose parents were either obese/overweight or normal
      weight/lean were selected from a population sample of families with twin births.
      Food and activity preferences were assessed with a combination of food intake and
      taste tasks, and questionnaires completed by the mother during a home visit.
      FINDINGS: Children from the obese/overweight families had a higher preference for
      fatty foods in a taste test, a lower liking for vegetables, and a more
      'overeating-type' eating style. They also had a stronger preference for sedentary
      activities, and spent more time in sedentary pastimes. There were no differences
      in speed of eating or reported frequency of intake of high-fat foods. CONCLUSION:
      Part of the process whereby a genetic risk of obesity is transmitted to the next
      generation could be through differences in diet and activity preferences, which
      would place susceptible individuals at risk of positive energy balance in the
      permissive nutritional environment of industrialised countries today.

PMID- 11443495
TI  - Does waist circumference predict fat gain in children?
AB  - OBJECTIVE: The aim of this study was to identify in a group of 8-y-old
      prepubertal children the anthropometric parameter with the highest prediction
      power of overweight, measured 4 y later. SUBJECTS: One-hundred and twelve
      Caucasian children (54 males, 58 females), aged 8.7+/-0.9 y, were studied.
      RESULTS: An analysis of the association between relative body mass index (BMI) at
      follow-up (%) and some indexes of adiposity like relative BMI (%), waist
      circumference, subscapular and triceps skinfolds, the sum of four skinfolds and
      percentage fat mass measured at baseline, showed that relative BMI (relBMI) at
      baseline had the highest association with relBMI at follow-up (r=0.77; P<0.001);
      waist circumference had a slightly lower significant association with relBMI at
      follow-up (r=0.74; P<0.001). In a multiple regression analysis, waist
      circumference (adjusted for age) accounted for approximately 64% of the variation
      of relBMI at follow-up (P<0.001). RelBMI measured at baseline accounted for
      approximately 59% of the variation of relBMI at follow-up (P<0.001). Multiple
      logistic regression analysis included waist circumference, adjusted for age,
      mother's BMI and relBMI measured at baseline as independent variables in the
      final equation. In particular, each centimeter increase of waist circumference at
      the age of 8 y doubled the risk of having a relBMI greater than 120% at the age
      of 12 y. CONCLUSION: The results of this study, the first which has approached
      this investigation in children, showed that waist circumference measured at the
      age of 8 y, which is simple to perform and easy to reproduce, may be a promising
      index to assess adiposity as well as to predict overweight at puberty.

PMID- 11443496
TI  - Serum lipids, serum insulin, plasma fibrinogen and aerobic capacity in obese and
      non-obese Singaporean boys.
AB  - OBJECTIVES: To compare blood lipids, lipoproteins, apoproteins, fibrinogen,
      insulin and aerobic capacity in obese and non-obese Chinese Singaporean boys. To
      examine relationships between blood metabolites, body composition and aerobic
      capacity in these groups. DESIGN: Cross-sectional. SUBJECTS: Forty Chinese
      Singaporean boys aged 13-15 y. Classified as obese (n=20) or non-obese (n=20)
      based on adiposity (fat mass/fat free mass): >0.60=obese, <0.40=non-obese.
      MEASUREMENTS: Body composition (dual energy X-ray absorptiometry), waist
      circumference, peak oxygen consumption (VO(2) peak), serum concentrations of
      total cholesterol, triacylglycerol, high density lipoprotein cholesterol (HDL-C),
      total cholesterol/HDL-C, apoproteins AI and B, lipoprotein(a), insulin and
      glucose. Plasma concentration of fibrinogen. RESULTS: Obese boys had
      significantly (P<0.01) higher (mean+/-s.d.) concentrations of serum
      triacylglycerol (1.51+/-0.65 vs 1.04+/-0.34 mmol/l), serum insulin (24.1+/-11.5
      vs 12.3+/-4.45 mU/l) and plasma fibrinogen (4.01+/-0.54 vs 3.35+/-0.76 g/l) than
      non-obese boys. Within the non-obese group plasma fibrinogen concentration was
      significantly related to percentage body fat (r=0.546, P<0.05). VO(2) peak
      relative to body mass (ml/kg/min or ml/kg(-0.67)/min) was significantly (P<0.001)
      lower in obese compared to non-obese boys but absolute VO(2) peak (l/min),
      adjusted for fat-free mass via analysis of covariance, was higher in obese than
      non-obese boys (P<0.01). Partial correlations revealed that none of the blood
      metabolites were significantly related to VO(2) peak independent of body fatness.
      CONCLUSIONS: Obesity was related to elevated concentrations of serum
      triacylglycerol, serum insulin and plasma fibrinogen in Chinese Singaporean boys.
      These elevated concentrations did not appear to be associated with a lower
      aerobic capacity (independent of body fatness) in the obese.

PMID- 11443497
TI  - Transmissibility of adenovirus-induced adiposity in a chicken model.
AB  - BACKGROUND: We previously reported that human adenovirus Ad-36 induces adiposity
      and paradoxically lower levels of serum cholesterol (CHOL) and triglycerides (TG)
      in animals. OBJECTIVE: To evaluate the transmissibility of Ad-36 and Ad-36
      induced adiposity using a chicken model. DESIGN: Experiment 1--four chickens were
      housed (two per cage) and one from each cage was inoculated with Ad-36. Duration
      of presence of Ad-36 DNA in the blood of all chickens was monitored. Experiment 2
      -two groups of chickens were intranasally inoculated with Ad-36 (infected donors,
      I-D) or media (control donors, C-D). Blood drawn 36 h later from I-D and C-D
      groups was inoculated into wing veins of recipient chickens (infected receivers,
      I-R, and control receivers, C-R, respectively). On sacrifice, 5 weeks post
      inoculation, blood was drawn, body weight noted and visceral fat was separated
      and weighed. RESULTS: Experiment 1--Ad-36 DNA appeared in the blood of the
      inoculated chickens and that of uninoculated chickens (cage mates) within 12 h of
      inoculation and the viral DNA persisted up to 25 days in the blood. Experiment 2-
      compared with C-D, visceral and total body fat were significantly greater and
      CHOL significantly lower for the I-D and I-R. TG were significantly lower for the
      I-D. Ad-36 was isolated from 12 out of 16 blood samples of the I-D that were used
      for inoculating I-R chickens. Ad-36 DNA was present in the blood and the adipose
      tissue of the I-D and I-R but not in the skeletal muscles of animals selected
      randomly for testing. CONCLUSION: As seen in experiment 1, Ad-36 infection can be
      transmitted horizontally from an infected chicken to another chicken sharing the
      cage. Additionally, experiment 2 demonstrated blood-borne transmission of Ad-36
      induced adiposity in chickens. Transmissibility of Ad-36-induced adiposity in
      chicken model raises serious concerns about such a possibility in humans that
      needs further investigation.

PMID- 11443498
TI  - NMDA receptor-mediated modulation of ventilation in obese Zucker rats.
AB  - BACKGROUND: Ventilation in response to hypoxia is reduced in some obese humans
      and is believed to represent part of the pathogenesis of obesity hypoventilation
      syndrome (OHS). Ventilation in response to hypoxic exposure is closely related to
      the release of excitatory neurotransmitters, in particular glutamate, acting
      specifically on N-methyl-D-aspartate (NMDA) receptors. OBJECTIVES: The aim of the
      present study was to investigate whether NMDA receptor-mediated mechanisms are
      responsible for the altered ventilatory response to sustained hypoxia observed in
      obese Zucker (Z) rats. SUBJECTS: Seven lean and seven 15-week-old obese male Z
      rats were studied. MEASUREMENTS: Ventilation ([V](E)) at rest and during 30 min
      sustained hypoxic (10% O(2)) exposure was measured by the barometric method.
      [V](E) was assessed following the blinded-random administration of equal volumes
      of either saline (vehicle) or dextromethorphan (DM, 10 mg/kg), a non-competitive
      glutamate NMDA receptor antagonist. RESULTS: DM had no effects on resting [V(E)
      in both lean and obese rats during room air breathing. Lean rats treated with DM
      exhibited a significant (P<0.05) depression in [V](E), V(T), and V(T)/T(I) during
      either the early (5 min) or the late phase (30 min) of ventilatory response to
      sustained hypoxia. In contrast, DM administration in obese rats did not change
      [V(E), V(T), or V(T)/T(I) during the early phase of ventilatory response to
      hypoxia. During the late phase of ventilatory response to hypoxia. obese rats
      treated with DM exhibited a similar depression in [V](E) and V(T) as observed in
      lean rats, but had no significant change in V(T)/T(I) during the 30 min hypoxic
      exposure. CONCLUSION: Our findings indicate that altered glutamatergic mechanisms
      acting on NMDA receptors are partially responsible for a blunted early phase of
      ventilatory response to hypoxia noted in obese rats and also contribute to their
      reduced neural respiratory drive.

PMID- 11443499
TI  - The anorectic effect of a chronic peripheral infusion of amylin is abolished in
      area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats.
AB  - OBJECTIVE: Neurons in the area postrema/nucleus of the solitary tract (AP/NTS)
      region mediate amylin's anorectic effect elicited by a single intraperitoneal
      (i.p.) injection of a low dose (5 microg/kg). Here, we tested if a sustained
      elevation in amylin levels which was achieved by chronic amylin infusion reduces
      food intake by acting in the AP/NTS region or, possibly, at other brain sites.
      Further, we tested the role of the AP/NTS region in mediating the anorectic
      effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT)
      after an acute single injection. DESIGN: Amylin (2 microg/kg/h) was chronically
      infused i.p. by osmotic minipumps in AP/NTS-lesioned (AP-X) or sham-lesioned
      (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses
      of 0.5 (only sCT), 5 or 50 microg/kg. Food intake was measured by a computerized
      system. Body weight was assessed by manually weighing the rats. RESULTS: Amylin
      significantly reduced cumulative food intake for about 7 days in SHAM but not in
      AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size
      of nocturnal meals (eg average meal size during the first four dark phases; SHAM,
      NaCl 4.1+/-0.6 vs amylin 2.6+/-0.4 g; n=6, P<0.05; AP-X, 2.6+/-0.3 vs 3.7+/-0.3)
      while light phase food intake was unaffected. Body weight gain over the whole 14
      day infusion period was reduced by amylin in SHAM (NaCl 61+/-6 vs amylin 46+/-4
      g; P<0.05) but not in AP-X rats (54+/-4 vs 62+/-4). After single injection, the
      anorectic effect of high doses of amylin and sCT (50 microg/kg) was attenuated,
      but not abolished, in AP-X rats. CONCLUSION: We conclude that, under our
      experimental conditions, neurons in the AP/NTS region are necessary for
      chronically elevated peripheral amylin to reduce food intake in rats. High doses
      of amylin, however, may be able to overrun these receptors and reduce feeding by
      acting at other brain sites.

PMID- 11443500
TI  - Polymorphisms in the insulin response element of APOC-III gene promoter influence
      the correlation between insulin and triglycerides or triglyceride-rich
      lipoproteins in humans.
AB  - OBJECTIVE: To assess whether the -455 and -482 mutations in APOC-III gene insulin
      response element affect the relationships between plasma insulin and triglyceride
      rich lipoprotein levels. DESIGN: Population-based studies. SUBJECTS: The
      population sample was composed of 983 subjects (485 men and 498 women), aged
      between 35 and 65 y, randomly sampled from the electoral rolls in Northern France
      and stratified on gender and 10 y age groups. MEASUREMENTS: Plasma triglyceride,
      apolipoprotein C-III, apoB, LpC-III:B and LpE:B lipoprotein particles and insulin
      levels were measured. Two polymorphisms in APOC-III gene insulin response element
      (T-->C at -455 and/or C-->T at -482) were determined. RESULTS: Plasma insulin was
      positively correlated to triglyceride levels (P<0.0001), apo C-III (P<0.003), LpC
      III:B (P<0.0001), apoB (P<0.0001) and LpE:B (P<0.0001). This association differed
      significantly according to APOC-III insulin response element polymorphisms. The
      relationship between insulin and LpC-III:B (P<0.02) or apoB (P<0.02) was greater
      in women bearing the C allele of -455 than the T allele. Similarly, the
      relationship between insulin and LpC-III:B (P<0.02) or LpE:B (P<0.05) was greater
      in women bearing the T allele of -482 than the C allele. There was no evidence
      for any effect in men. CONCLUSION: These results suggest that the relationship
      between plasma insulin and triglyceride-rich lipoprotein levels is partly
      influenced by polymorphisms in APOC-III insulin response element.

PMID- 11443501
TI  - TNFalpha and leptin inhibit basal and glucose-stimulated insulin secretion and
      gene transcription in the HIT-T15 pancreatic cells.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNFalpha), a cytokine produced at
      inflammatory sites and in adipose tissue, is known primarily for its detrimental
      effects on insulin action. There is evidence to suggest that TNFalpha may also
      influence beta-cell function. Leptin is another adipose tissue-derived hormone
      that might also act on beta-cells. OBJECTIVE: We explored the independent and
      combined effects of TNFalpha and leptin upon basal and glucose-stimulated insulin
      transcription and secretion in the HIT-T15 pancreatic beta cell line. METHODS:
      Cells were cultured for 40 h in the presence of near-normal basal (7 mM) or high
      (16.7 mM) glucose and treated with either TNFalpha (1, 10 and 50 ng/ml) or leptin
      (10, 50 and 100 ng/ml) or both together. Insulin concentrations were measured by
      radioimmunoassay. Insulin mRNA levels were evaluated by a semi-quantitative
      reverse transcription-polymerase chain reaction (RT-PCR) method, after
      normalization with beta-actin mRNA. RESULTS: TNFalpha significantly suppressed
      basal and glucose-stimulated insulin secretion and proinsulin mRNA transcription
      in a dose-dependent manner, an effect that was more powerful in the presence of
      high glucose. Leptin also inhibited dose-dependent insulin mRNA and protein at
      both glucose concentrations, but did not appear to further potentiate the
      suppressive effects of TNFalpha. CONCLUSION: TNFalpha suppresses both basal and
      glucose-stimulated insulin transcription and secretion in HIT-T15 cells, an
      effect that is enhanced significantly by high glucose. Leptin also independently
      inhibits basal and glucose-stimulated insulin secretion and transcription but
      does not modify TNFalpha effects. These effects might contribute to the
      abnormalities of glucose metabolism that characterize conditions of increased
      TNFalpha and/or leptin production.

PMID- 11443502
TI  - Adipose depot-specific expression of cIAP2 in human preadipocytes and modulation
      of expression by serum factors and TNFalpha.
AB  - BACKGROUND: Visceral obesity is more closely associated with many deleterious
      metabolic sequelae than obesity per se. The identification of properties that
      distinguish fat cells of the omentum from adipocytes situated elsewhere in the
      body may lead to the development of therapeutic strategies targeting visceral
      obesity. We have previously demonstrated that cIAP2 mRNA is significantly
      overexpressed in omental (Om) compared with subcutaneous (Sc) adipocytes. This
      molecule is involved in the TNFalpha signalling pathway and may inhibit
      apoptosis. OBJECTIVE: To examine the effect of serum agents and TNFalpha upon
      cIAP2 mRNA expression in human primary culture preadipocytes. DESIGN: Paired
      omental and subcutaneous adipose tissue biopsies were obtained from 11 patients,
      nine female and two male, with ages ranging from 29 to 82. These were cultured in
      either serum containing medium or serum-free medium with or without the addition
      of TNFalpha for 4 h and mRNA levels analysed by quantitative reverse
      transcription polymerase chain reaction. RESULTS: When human preadipocytes were
      cultured in a defined medium containing foetal calf serum the Om cells had a
      greater level of expression of cIAP2 mRNA than Sc cells from the same individual
      (mean 3.5-fold higher Sc>Om; P<0.01). However, when serum was removed from this
      media for a transitory period the level of cIAP2 mRNA decreased in the omental
      depot such that Sc preadipocytes had greater cIAP2 expression than their Om
      counterparts. Addition of TNFalpha induced a large increase in mRNA levels of
      cIAP2 (mean 20-fold). CONCLUSIONS: These results demonstrate that cIAP2 is
      expressed in a depot-specific manner in human preadipocytes and that levels of
      expression are regulated by serum factors and TNFalpha. Thus there may be
      intrinsic differences between preadipocyte cells from different adipose depots
      and this may play a role in the regulation of body fat distribution via the
      modulation of fat cell apoptosis.

PMID- 11443503
TI  - Heritability of obesity-related traits among Nigerians, Jamaicans and US black
      people.
AB  - OBJECTIVE: The mean values for anthropometric traits vary across population
      groups and this variation is clearly determined for the most part by the
      environment. The familiarity of anthropometric traits also varies in reports from
      different populations, although this variation has not been shown to follow a
      consistent pattern. To examine whether heritability is influenced by socio
      cultural factors, we conducted a cross-cultural study of populations of the
      African diaspora. PARTICIPANTS: Data were collected on 1868 family members from
      Nigeria, 623 from Jamaica and 2132 from metropolitan Chicago, IL, USA.
      MEASUREMENTS: Height and weight were measured and body mass index (kg/m(2))
      calculated. Fat-free mass, fat mass and percentage body fat were estimated using
      bioelectrical impedance analysis. Plasma leptin concentrations were also
      measured. The proportion of variance attributable to additive genetic and non
      shared environmental components was estimated with the maximum likelihood
      variance decomposition method. RESULTS: Mean values for all anthropometric traits
      increased along the socio-cultural gradient, and obesity increased from 5% in
      Nigeria to 23% in Jamaica and 39% in the USA. Within populations the
      relationships among traits both within individuals and within families were
      highly consistent. Heritability estimates for weight, body mass index, fat mass
      and percentage body fat were approximately 50% for all groups. Heritability for
      height was lower in Nigeria (62%) than in Jamaica (74%) or the US (87%).
      CONCLUSION: The familial patterns of body size and energy storage appear to be
      consistent in these genetically related populations across a wide range of
      environmental conditions.

PMID- 11443504
TI  - Risk factors for coronary heart disease in obese non-diabetic subjects.
AB  - OBJECTIVE: To examine relationships between body mass index (BMI) and coronary
      risk factors in obese subjects presenting to a dedicated obesity clinic. STUDY
      DESIGN: Cross-sectional population survey from a single centre. SUBJECTS: Three
      hundred and eighty-six consecutive non-diabetic obese subjects (301 women, 85
      men) attending an obesity clinic for the first time (mean BMI 43.3 kg/m(2); range
      30.6-71.5), aged 17-69 y (mean 40.1). MEASUREMENTS: Height, weight, resting blood
      pressure, fasting plasma cholesterol, triglyceride, glucose and uric acid
      concentrations. RESULTS: All variables measured showed an increase with higher
      BMI (triglycerides, P=0.04; glucose, P=0.007; urate, P<0.001; systolic BP,
      P<0.001; diastolic BP, P<0.001) as measured by one-way ANOVA, except cholesterol
      concentration which showed no relationship with BMI. In comparison with the group
      of subjects with BMI 30-35 kg/m(2) mean values for all variables were higher in
      the more obese subjects. CONCLUSIONS: Non-diabetic subjects with BMI>35 kg/m(2)
      carry a burden of common coronary risk factors which appears to increase with
      greater obesity. The risk factor pattern observed echoes that described in
      insulin resistance syndromes. Plasma cholesterol concentration appears not to be
      related to BMI.

PMID- 11443505
TI  - Abdominal and total adiposity and risk of coronary heart disease in men.
AB  - BACKGROUND: Waist circumference is a simpler measure of abdominal adiposity than
      waist/hip ratio (WHR), but few studies have directly compared the two measures as
      predictors of coronary heart disease (CHD) in men. In addition, whether the
      association of abdominal adiposity is independent of total adiposity as measured
      by body mass index (BMI) in men remains uncertain. OBJECTIVE: To compare waist
      circumference and WHR as predictors of CHD in men, and to determine whether the
      association is independent of BMI. DESIGN: Prospective cohort study. METHODS: We
      compared WHR, waist circumference and BMI with risk of CHD (myocardial infarction
      or coronary revascularization) among men in the Physicians' Health Study, a
      randomized trial of aspirin and beta-carotene among 22 071 apparently healthy US
      male physicians, aged 40-84 y at baseline in 1982. Men reported height at
      baseline, and weight, waist and hip measurements on the 9 y follow-up
      questionnaire. RESULTS: Among the 16 164 men who reported anthropometric
      measurements and were free from prior CHD, stroke or cancer, a total of 552
      subsequent CHD events occurred during an average follow-up of 3.9 y. After
      adjusting for age, randomized study agent, smoking, physical activity, parental
      history of myocardial infarction, alcohol intake, multivitamin and aspirin use,
      men in the highest WHR quintile (>or=0.99) had a relative risk (RR) for CHD of
      1.50 (95% CI 1.14-1.98) compared with those in the lowest quintile (<0.90). Men
      in the highest waist circumference quintile (>or=103.6 cm) had a RR of 1.60 (CI,
      1.21-2.11) for CHD compared with men in the lowest quintile (<88.4 cm). Further
      adjustment for BMI substantially attenuated these associations: men in the
      highest WHR and waist circumference quintiles had relative risks for CHD of 1.23
      (CI, 0.92-1.66) and 1.06 (CI, 0.74-1.53), respectively. Men in the highest BMI
      quintile (>or=27.6 kg/m(2)) had a multivariate RR of CHD of 1.73 (CI, 1.29-2.32),
      after adjustment for WHR. No significant effect modification by age of the
      relationship between either measure of abdominal adiposity and risk of CHD was
      observed. CONCLUSIONS: These data support a modest relationship between abdominal
      adiposity, as measured by either WHR or waist circumference, and risk of CHD both
      in middle-aged and older men. However, abdominal adiposity did not remain an
      independent predictor of CHD after adjustment for BMI.

PMID- 11443506
TI  - Relationships between body weight change and cardiovascular disease risk factors
      in male former athletes.
AB  - OBJECTIVE: To evaluate the cardiovascular disease risk factor profile in former
      athletes according to their weight-change patterns during the postcompetitive
      period. DESIGN: Cohort study with a retrospective assessment of baseline weight
      of male former top-level athletes. SUBJECTS: One-hundred and fifty top-level
      athletes aged 35-60 y were divided into four groups according to the weight
      change patterns during the postcompetitive period (weight loss, constant weight,
      weight gain over 3.0 kg and weight gain over 10.0 kg). MEASUREMENTS:
      Anthropometric measurements (height, weight, BMI, percentage fat, skinfolds,
      waist-to-hip-ratio (WHR), resting systolic and diastolic blood pressure (SBP,
      DBP), serum lipids and lipoproteins (CHOL, HDL-C, LDL-C, TG), and physical
      working capacity. A questionnaire was drawn up to evaluate current and previous
      physical activity, lifestyle indices and to record weight at the age of 20
      (according to sports diaries). RESULTS: Weight gain over 10.0 kg in former
      athletes was closely associated with higher body mass index, percentage body fat,
      skinfold thickness, WHR, SBP, DBP, LDL-C and TG values, as well as lower HDL-C,
      HDL-C/CHOL ratio and physical working capacity values. After adjustment for
      confounders, the weight gainers over 10.0 kg revealed a higher risk of
      hypertension (OR 6.65; 95% CI 2.99-11.65), abdominal fat distribution pattern (OR
      10.51; 95% CI 6.11-16.24), elevated LDL-C (OR 1.88; 95% CI 1.15-3.06) and
      hypertriglyceridemia (OR 3.52; 95% CI 1.12-8.56) compared with those whose weight
      was constant. Weight loss and weight gain less than 10.0 kg were significantly
      related to increased risk for abdominal fat distribution pattern. CONCLUSION: The
      results of the present study showed that weight gain during the postcompetitive
      period was associated with a higher prevalence of cardiovascular disease risk
      factors in male former athletes.

PMID- 11443507
TI  - Effects of ten year body weight variability on cardiovascular risk factors in
      Japanese middle-aged men and women.
AB  - OBJECTIVE: The purpose of the present study was to determine the effects of
      weight variability on cardiovascular risk factors (CRF) based on a large sample
      of community-resident Japanese males and females. METHOD: A total of 3564 men and
      1955 women, all Japanese, aged 30-69 y in the baseline year (1987), were followed
      up for up to 10 y (end-point in 1996). Height, body weight, systolic and
      diastolic blood pressure, fasting serum total cholesterol, triglyceride and
      fasting plasma glucose were measured as an annual health check-up. At least six
      times in 10 y, body mass index (BMI) mean was calculated as an index of the BMI
      level of each subject (BMI mean). Direction and magnitude of the change in a
      subject's BMI was determined by a regression slope of BMI values over time (BMI
      slope). BMI fluctuation was defined as the root mean square error (BMI RMSE) of a
      regression line. The slopes of the five CRF were calculated using each regression
      equation over time. RESULTS: The BMI slope strongly correlated to each CRF slope
      independent of baseline age, baseline CRF value, smoking habit, BMI mean and BMI
      RMSE. BMI RMSE did not correlate to any CRF slopes. CONCLUSION: This study
      indicates that weight gain and weight loss have a much greater effect on CRF
      change than does weight fluctuation in Japanese middle-aged men and women.

PMID- 11443508
TI  - Relationship of obesity distribution and peripheral arterial occlusive disease in
      elderly men.
AB  - OBJECTIVE: To examine the relationships between total body fatness and abdominal
      fat distribution with peripheral arterial disease. DESIGN: Cross-sectional.
      SUBJECTS: Population-based sample of 708 men aged 55-74. MEASUREMENTS: Body mass
      index (BMI) to estimate total body fatness and waist-to-hip ratio for abdominal
      fat distribution; peripheral arterial disease defined by ankle/brachial index
      <0.9; cardiovascular risk factors. RESULTS: Peripheral arterial disease was
      observed in 13.4% of subjects. BMI did not correlate with peripheral arterial
      disease, whereas an increased waist-to-hip ratio over 0.966 (median value)
      doubled the prevalence of arterial disease. After controlling for smoking,
      diabetes, hypertension, high-density lipoprotein cholesterol and triglycerides,
      increased waist-to-hip ratio was independently associated with peripheral
      arterial disease (odds ratio 1.68; 95% confidence interval 1.05-2.70).
      CONCLUSION: Abdominal fat distribution, but not total body fatness, is associated
      with peripheral arterial occlusive disease, independently of concurrent
      cardiovascular risk factors.

PMID- 11443509
TI  - Biases in the mortality risk versus body mass index relationship in the NHANES-1
      Epidemiologic Follow-Up Study.
AB  - BACKGROUND: Conflicting research findings have created uncertainty as to the
      ideal body weight. OBJECTIVE: To test whether average-adulthood BMI (body mass
      index, weight in kilograms per height in meters squared) is a more reliable
      predictor of mortality risk than the one-time baseline BMI measurement which has
      been used in previous studies. DESIGN: Prospective cohort study with a 20 y
      follow-up period, the First National Health and Examination Survey (NHANES 1)
      Epidemiologic Follow-up Study (NHEFS). SUBJECTS: A random probability sample of
      14,407 adults aged 25-74 y in the 1971-1975 NHANES 1. MEASUREMENTS: Body-weight
      data were derived from measurements in the 1971-1975 and 1982-1984 NHEFS surveys,
      and current and recalled estimates by subjects in the 1971-1975, 1982-1984, 1986
      and 1987 surveys. Height was measured in the 1971-1975 survey. Socio-economic and
      lifestyle covariates were derived from questionnaires administered in all four
      surveys. Almost all deaths were verified by death certificates. RESULTS: The
      shape of the morality risk vs baseline BMI curve varied due to a bias (late-life
      bias) caused by a steep decrease in BMI among the elderly toward the end of the
      lifespan. In a particular analysis, the portion of subjects at baseline who were
      deceased elderly with lower BMI than age-matched censored subjects indicated the
      size of the bias, and appeared to be the proximate cause. Strong evidence was
      found to support the proximate cause being the actual cause. Excluding deaths
      during early follow-up was only able to remove the late-life bias in limited
      circumstances. Using average-adulthood BMI as mortality predictor and baseline
      BMI as covariate was very effective in removing the late-life bias. It also
      appeared to remove the reverse-causation and regression-dilution biases, and
      yielded robustly positive mortality risk vs average-adulthood BMI curves in all
      analyses in which it was tested. CONCLUSIONS: Average-adulthood BMI appears to be
      an appropriate predictor of mortality risk, provided baseline BMI is used as a
      covariate. Among non-elderly persons, being leaner meant a lower mortality risk,
      down to the lowest category of leanness in the study-<20 kg/m(2). Future survival
      analyses of the mortality-BMI relationship should account for the effects of the
      regression-dilution, reverse-causation and late-life biases.

PMID- 11443510
TI  - Weight gain and its predictors in Chinese adults.
AB  - OBJECTIVE: To describe 8 y weight change in Chinese adults and to determine the
      baseline characteristics of those who gained weight. DESIGN: A population-based
      cohort study of weight change and its predictors from 1989 to 1997. PARTICIPANTS:
      A cohort of 2488 adults aged 20-45 in 1989 drawn from seven provinces in China
      using multistage, random cluster sampling. MEASUREMENTS: Weight change over 8 y
      was the outcome variable. The key exposures were baseline energy intake, physical
      activity at work, alcohol consumption and smoking status. Baseline weight, weight
      status, height, age, residence, income and educational attainment were control
      variables. RESULTS: Overweight (body mass index, BMI>or=25 kg/m(2)) doubled in
      females (10.4-20.8%) and almost tripled in males (5.0-14.1%). Low physical
      activity was a strong predictor of weight gain. Compared to those whose weight
      remained stable (+/-2 kg/8 y), males and females who experienced large weight
      gain (>5 kg/8 y) were 3 and 1.8 times more likely to engage in light rather than
      heavy work-related physical activity. CONCLUSION: The prevalence of overweight
      increased dramatically in this cohort. Light work-related physical activity was
      the strongest predictor of this weight gain.

PMID- 11443511
TI  - The effects of 2-week ingestion of (--)-hydroxycitrate and (--)-hydroxycitrate
      combined with medium-chain triglycerides on satiety, fat oxidation, energy
      expenditure and body weight.
AB  - OBJECTIVE: Assessment of the effect of 2-week supplementation with (--)
      hydroxycitrate (HCA) and HCA combined with medium-chain triglycerides (MCT) on
      satiety, fat oxidation, energy expenditure (EE) and body weight (BW) loss.
      DESIGN: Three intervention periods of 2 weeks separated by washout periods of 4
      weeks. Double-blind, placebo-controlled, randomised and cross-over design.
      SUBJECTS: Eleven overweight male subjects (mean+/-s.d.; age, 47+/-16 y; body mass
      index, 27.4 +/- 8.2 kg/m(2)). INTERVENTION: Subjects consumed three self-selected
      meals and four iso-energetic (420 kJ) snacks daily with either no supplementation
      (PLA), 500 mg HCA (HCA) or 500 mg HCA and 3 g MCT (HCA+MCT). Each intervention
      ended with a 36 h stay in the respiration chamber. RESULTS: There was a
      significant BW loss during the 2 weeks of intervention (PLA, -1.0 +/- 0.4 kg,
      P<0.05; HCA, -1.5 +/- 0.5 kg, P<0.01; HCA+MCT, -1.3 +/- 0.2 kg, P<0.001), but
      this reduction was not different between treatments. 24 h EE (PLA, 11.8 +/- 0.2
      MJ; HCA, 11.7 +/- 0.1 MJ; HCA+MCT, 11.5 +/- 0.1 MJ), 24 h RQ (0.85 +/- 0.00 in
      all treatments) and the area under the curve of the appetite-related parameters
      were not different between treatments. CONCLUSION: Two-week supplementation with
      HCA and HCA combined with MCT did not result in increased satiety, fat oxidation,
      24 h EE or BW loss compared to PLA, in subjects losing BW.

PMID- 11443512
TI  - Gastrointestinal side effects of orlistat may be prevented by concomitant
      prescription of natural fibers (psyllium mucilloid).
AB  - OBJECTIVES: This placebo-controlled open study was designed to test the
      hypothesis that most of the gastrointestinal (GI) side events induced by
      treatment of obese patients with orlistat (a gastrointestinal lipase inhibitor)
      could be prevented or ameliorated by concomitant use of natural fibers (psyllium
      mucilloid). DESIGN: Two groups of obese women (BMI>27 kg/m(2)) were treated with
      orlistat 120 mg three times a day. One group (A, n=30) was randomized to receive
      orlistat and, approximately 6.0 g of orange-flavored psyllium mucilloid dissolved
      in water and the other group (B, n=30) received orlistat and orange-flavored
      placebo. At the end of 30 days and 2 weeks of washout, group A switched to
      placebo and group B received psyllium while continuing orlistat three times a
      day. SUBJECTS: Sixty professional women, more than 21-y-old with a body mass
      index (BMI) between 27.3 and 48.0 kg/m(2), who were not receiving any other
      medication. MEASUREMENTS: Assessments included weekly visits to attending
      physician, filling a form in which GI events were recorded, monthly measurements
      of body weight, blood pressure and serum lipids. The frequency and severity of GI
      events were evaluated by a score system, based on information provided by the
      patients. RESULTS: Both groups A and B significantly lost (P<0.01) weight after
      60 days of orlistat (A=96.8 to 94.9 kg and B=98.7 to 96.5 kg). Similarly, BMI
      values declined significantly in both groups. While in the psyllium plus orlistat
      group (group A) the mean +/-s.e.m. of the scores reflecting GI events was 13.0+/
      1.8, the placebo plus orlistat group (B) had a value of 35.9+/-2.7 (P<0.01). When
      the reverse situation was instituted the placebo and orlistat group presented a
      mean score of 36.1+/-3.6 and the psyllium plus orlistat a mean score of 8.9+/-1.5
      (P<0.01). CONCLUSIONS: Psyllium hydrophilic mucilloid concomitantly prescribed to
      obese patients receiving 120 mg of orlistat three times a day is an effective and
      safe adjunct therapy that is helpful in controlling the GI side effects of this
      pancreatic lipase inhibitor.

PMID- 11443513
TI  - Inverse relationship between calf and breast size in obese females.

PMID- 11443516
TI  - Association of a GTP-binding protein Go alpha subunit mutation with
      schizophrenia.

PMID- 11443517
TI  - The role of genes and family in trauma exposure and posttraumatic stress
      disorder.

PMID- 11443518
TI  - Proposed endophenotypes of dysthymia: evolutionary, clinical and pharmacogenomic
      considerations.
AB  - Dysthymia is highly prevalent--though underdiagnosed--occurring in at least 3% of
      the population. We conceptualize it as the clinical extension of adaptive traits
      that have developed during evolution to cope with stress and failure. A
      classification of dysthymias into anxious and anergic subtypes--and their
      putative association to bipolarity--is proposed. We further posit neurochemical
      and neurophysiological substrates for the two subtypes. A better recognition and
      understanding of dysthymic subtypes and their respective place in the affective
      spectrum will increase the proportion of people that may benefit from targeted
      treatments. It would also expand the pool of subjects that may be enrolled in
      genetic and pharmacogenomic research studies.

PMID- 11443519
TI  - MAO-A and COMT polymorphisms and gene effects in narcolepsy.
AB  - Narcolepsy presents one of the tightest associations with a specific HLA antigen
      (DQB1*0602) but there is strong evidence that non-HLA genes also confer
      susceptibility. Recent observations have implicated the hypocretin/orexin system
      in narcolepsy in both humans and animals. In addition, the implication of
      monoaminergic systems in the pathophysiology of narcolepsy is well established
      and a significant association between the monoamine oxydase-A (MAO-A) gene and
      human narcolepsy has recently provided a possible genetic link. We investigated
      polymorphisms of MAO-A and catechol-O-methyltransferase (COMT) in 97 Caucasians
      with well-defined narcolepsy-cataplexy and sought for genotypic effects on
      disease symptoms. No evidence of association between genotype or allele
      frequencies of both MAO-A or COMT gene and narcolepsy was found. However, a
      sexual dimorphism and a strong effect of COMT genotype on disease severity were
      found. Women narcoleptics with high COMT activity fell asleep twice as fast as
      those with low COMT activity during the multiple sleep latency test (MSLT) while
      the opposite was true for men. COMT genotype also strongly affected the presence
      of sleep paralysis and the number of REM sleep onsets during the MSLT. In
      agreement with well-documented pharmacological results in canine narcolepsy, this
      study reports the first genetic evidence for the critical involvement of the
      dopaminergic and/or noradrenergic systems in human narcolepsy.

PMID- 11443520
TI  - RNA editing of the 5-HT(2C) receptor is reduced in schizophrenia.
AB  - 5-HT(2C) receptor (5HT(2C)R, serotonin-2C) RNA undergoes editing to produce
      several receptor variants, some with pharmacological differences. This
      investigation comprised two parts: the characterisation of 5-HT(2C)R RNA editing
      in a larger human control sample than previously examined, and a comparative
      study in subjects with schizophrenia. Secondary structure analysis of the
      putative edited region of the human 5-HT(2C)R gene predicted the existence of a
      double stranded (ds) RNA loop, essential for RNA editing in this receptor. RNA
      was then extracted from frontal cortex of five controls and five subjects with
      schizophrenia. RT-PCR products of the edited region were cloned and sequenced (n
      = 100). Reduced RNA editing, increased expression of the unedited 5-HT(2C-INI)
      isoform in schizophrenia (P = 0.001) and decreased expression of the 5-HT(2C-VSV)
      and 5-HT(2C-VNV) isoforms were detected in the schizophrenia group. In addition,
      two novel mRNA edited variants were identified: 5-HT(2C-MNI) and 5-HT(2C-VDI).
      Screening of the 5-HT(2C)R gene did not reveal any mutations likely to disrupt
      the dsRNA loop, suggesting that the reduced RNA editing in schizophrenia may
      instead be caused by altered activity of the editing enzyme(s). Since the
      unedited 5-HT(2C-INI) is more efficiently coupled to G proteins than the other
      isoforms, its increased expression in schizophrenia may lead to enhanced 5
      HT(2C)R-mediated effects. The results also illustrate that potentially important
      receptor alterations may occur in schizophrenia which are not detectable merely
      in terms of receptor abundance.

PMID- 11443521
TI  - The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down
      regulated by the antipsychotic drug clozapine.
AB  - We show here that clozapine, a beneficial antipsychotic, down-regulates the
      expression of the glutamate transporter GLT-1 in the rat cerebral cortex, thereby
      reducing glutamate transport and raising extracellular glutamate levels.
      Clozapine treatment (25--35 mg kg(-1) day(-1) orally) reduced GLT-1
      immunoreactivity in several brain regions after 3 weeks; this effect was most
      prominent after 9 weeks and most evident in the frontal cortex. GLT-1 protein
      levels were reduced in the cerebral cortex of treated rats compared with controls
      and were more severely affected in the anterior (71.9 +/- 4.5%) than in the
      posterior (53.2 +/- 15.4%) cortex. L-[(3)H]-glutamate uptake in Xenopus laevis
      oocytes injected with mRNA extracted from the anterior cerebral cortex of rats
      treated for 9 weeks was remarkably reduced (to 30.6 +/- 8.6%) as compared to
      controls. In addition, electrophysiological recordings from oocytes following
      application of glutamate revealed a strong reduction in glutamate uptake currents
      (46.3 +/- 10.2%) as compared to controls. Finally, clozapine treatment led to
      increases in both the mean basal (8.1 +/- 0.7 microM) and the KCl-evoked (28.7 +/
      7.7 microM) output of glutamate that were 3.1 and 3.5, respectively, higher than
      in control rats. These findings indicate that clozapine may potentiate
      glutamatergic synaptic transmission by regulating glutamate transport.

PMID- 11443522
TI  - Mutation analysis of SYNJ1: a possible candidate gene for chromosome 21q22-linked
      bipolar disorder.
AB  - Genes involved in the regulation of synaptic vesicle function are potential
      candidates for the development of psychiatric disorders. In addition to
      experimental and theoretical considerations, a number of genes involved in
      synaptic vesicle function map to regions of the genome that have been linked to
      bipolar disorder (BPD) and schizophrenia (SZ). One is synaptojanin 1 (SYNJ1)
      which maps to 21q22.2, a chromosomal region that has been linked to BPD in a
      subset of families in several studies. Synaptojanin 1 is an inositol 5
      phosphatase that has an important role in synaptic vesicle endocytosis. Mutation
      screening of 32 exons, intron--exon junctions, and 839 bases of 5'-flanking DNA
      resulted in the identification of 11 mutations of which four were very common and
      seven were very rare. Of the 11 mutations identified, several may have functional
      significance including two coding variants, two that may affect the binding of a
      transcription factor, and two that involve known splicing regulatory domains.
      Five bipolar patients out of 149 analyzed were found who have one of the four
      rare variants that were most likely to have functional significance compared with
      0/148 controls. The allele frequencies for three of the four common variants were
      very similar in bipolar patients and controls. A slight difference in allele
      frequency was found for an interesting mutation we detected in intron 12 in which
      two non-adjacent thymidine residues are deleted in a poly-AT tract located near
      the exon 12 splice donor site (chi(2) = 2.45, P = 0.12, 2-tailed). Although we
      failed to unequivocally identify a specific SYNJ1 allele that could be
      responsible for putative chromosome 21q22-linked BPD, several interesting
      variants were found to be increased in bipolar subjects and should be further
      investigated.

PMID- 11443523
TI  - A genome screen of a large bipolar affective disorder pedigree supports evidence
      for a susceptibility locus on chromosome 13q.
AB  - Bipolar affective disorder is a severe mood disorder that afflicts approximately
      1% of the population worldwide. Twin and adoption studies have indicated that
      genetic factors contribute to the disorder and while many chromosomal regions
      have been implicated, no susceptibility genes have been identified. In this
      present study, we undertook a 10 cM genome screen using 400 microsatellite
      markers in a large multigenerational bipolar pedigree consisting of 40
      individuals, including six affecteds. We found strongest evidence for linkage to
      chromosome 13q14. A maximum NPL score of 4.09 (P = 0.008) was obtained between
      markers D13S1272 and D13S153 using GENEHUNTER. A maximum two-point LOD score of
      2.91 (theta = 0.0) was found for marker D13S153 and a maximum three-point LOD
      score of 3.0 was obtained between markers D13S291 and D13S153 under a recessive
      model with 90% maximum age-specific penetrance and including bipolar I and
      unipolar individuals as affected. Several other markers in the region, D13S175,
      D13S218, D13S263, and D13S156 had two-point LOD scores greater than 1.5. These
      results meet the criteria for evidence of suggestive linkage. Haplotype analysis
      enabled us to narrow the likely disease region to a 6 cM region between markers
      D13S1272 and D13S1319, which contains the serotonin 2A receptor candidate gene.
      Two single nucleotide polymorphisms were identified in this gene but we did not
      detect any significant differences in allele frequency in a case-control sample.
      The region on chromosome 13q14-32 has previously been implicated in other bipolar
      and schizophrenia cohorts. Our results provide further support for the existence
      of a susceptibility locus on chromosome 13q14.

PMID- 11443524
TI  - Common effects of chronically administered antipanic drugs on brainstem GABA(A)
      receptor subunit gene expression.
AB  - Panic disorder is an anxiety disorder that can be treated by long-term
      administration of tricyclic antidepressants such as imipramine, monoamine oxidase
      inhibitors such as phenelzine, or the selective serotonin reuptake inhibitor
      (SSRI) antidepressants. Clinical data also indicate that some benzodiazepines,
      such as alprazolam, are effective antipanic agents, and that their therapeutic
      onset is faster than that of antidepressants. Benzodiazepines are well known for
      their action at GABA(A) receptors, and preclinical data indicate that imipramine
      and phenelzine also interfere with the GABAergic system. In addition some
      clinical data lend support to decreased benzodiazepine-sensitive receptor
      function in panic disorder patients. Using imipramine, phenelzine and alprazolam,
      we investigated, in rats, the possibility that the therapeutic efficacy of
      antipanic agents stems from the remodeling of GABAergic transmission in the pons
      medulla region. Of the 12 GABA(A) receptor subunit (alpha 1--6, beta 1--3, gamma
      1--3) steady-state mRNA levels investigated, we observed an increase in the
      levels of the alpha 3-, beta 1- and gamma 2-subunit transcripts with all three
      antipanic agents tested. The effects of imipramine and phenelzine on these
      subunits occurred after 21 days of treatment, while alprazolam effects were
      observed after 3 days of administration. Histochemical data suggest that the
      alpha 3 beta 1 gamma 2 subunits comprise a receptor subtype in the pons-medulla
      region. Therefore, we conclude that these molecular events parallel the
      therapeutic profile of the drugs examined. We further propose that these events
      may correspond to a remodeling of the GABA(A) receptor population, and may be
      useful markers for investigation of the antipanic properties of drugs.

PMID- 11443525
TI  - D10S1423 identifies a susceptibility locus for Alzheimer's disease in a
      prospective, longitudinal, double-blind study of asymptomatic individuals.
AB  - Typical, later-onset forms of Alzheimer's disease (AD) appear to be influenced by
      multiple susceptibility loci, combinations of which contribute to the development
      of this disorder. We previously reported the results of a systematic survey of
      the human genome for the identification of highly informative DNA polymorphisms
      (SSTRPs) that target new AD risk genes. In addition to the APOE locus, our survey
      detected five new candidate susceptibility loci for AD, including D10S1423. An
      association of the D10S1423 234-bp allele with AD has been reported in three
      independent samples of AD cases and controls (Boston, Pittsburgh, Bonn). Data
      from our case-control studies suggest a strong synergistic interaction between
      the D10S1423 234-bp and APOE E4 risk alleles (234-bp carrier: OR = 2.5, 95% CI =
      1.4--4.5; E4 carrier: OR = 8.3, 95% CI = 4.3--15.8; both alleles: OR = 23.1, 95%
      CI = 5.3--99.5). This report describes the prospective, longitudinal, double
      blind assessment of the age-specific risk of AD encountered by 325 asymptomatic
      first-degree relatives of AD probands who carried the D10S1423 234-bp allele, the
      APOE E4 allele, or both, after 11.5 years of systematic follow-up. A total of 18
      incident cases of AD were detected during the first 3379 subject-years of this
      longitudinal study. The effects of carrying either or both of the D10S1423 234-bp
      and APOE E4 alleles on the age-specific risk of developing AD were determined
      using Kaplan-Meier survival analysis. The age-specific risk of developing AD was
      the greatest for individuals who carried both alleles (Mantel--Cox statistic =
      20.12, df = 3, P = 0.0002; Breslow statistic = 13.36, df = 3, P = 0.004). Cox
      proportional hazards models were developed to estimate the risk ratios for each
      genotype, controlling for the potential effects of age at recruitment, sex, and
      years of education. In the resulting best fitting model, only individuals who
      carried both risk alleles exhibited a risk ratio that differed significantly from
      1 (risk ratio = 16.2, P = 0.008, 95% CI = 2.1--128.3). After controlling for
      these genotypes, female gender was also significantly associated with increased
      risk of developing AD (risk ratio = 5.1, P = 0.02, 95% CI = 1.2--21.1). Neither
      age at recruitment nor years of education made significant contributions to the
      model.

PMID- 11443526
TI  - Dopa decarboxylase gene polymorphisms and attention deficit hyperactivity
      disorder (ADHD): no evidence for association in the Irish population.
AB  - Dopa decarboxylase (DDC) is an enzyme which catalyses the decarboxylation of both
      dopa to dopamine and L-5 hydroxytryptophan to serotonin. Both catecholamines are
      major neurotransmitters of the mammalian nervous system. It has been suggested
      that genes involved in the dopaminergic system play a primary role in
      predisposing to attention deficit hyperactivity disorder (ADHD). In this study,
      the 4-bp insertion/deletion variant mapped to the first neuronally expressed exon
      1 at the dopa decarboxylase gene and two microsatellite markers flanking the gene
      were investigated for possible association with ADHD. Using HHRR, we observed an
      increased transmission (though not significant) of the 4-bp insertion (allele 1)
      to ADHD cases (chi(2) = 2.72, P = 0.1, RR = 1.25). However marginally significant
      excess transmission of allele 10 (213 bp) of the 3' microsatellite D7S2422 (
      approximately 0.75 cM distal to dopa decarboxylase gene) was found (chi(2) = 4.2,
      P = 0.04, RR=1.48). Interestingly, a haplotype containing both alleles is
      transmitted more frequently (chi(2)= 5, P = 0.025). Analysing data by the sex of
      transmitting parent showed a greater relative risk for paternal transmission of
      the 4-bp insertion allele and allele 10 of the D7S2422 (RR = 1.48 and 1.63
      respectively). This provides preliminary evidence that this locus or a closely
      mapped DNA variant may be involved in the genetic susceptibility to ADHD.
      However, further studies are required to either confirm or refute these
      observations.

PMID- 11443527
TI  - Association study of a dopamine transporter polymorphism and attention deficit
      hyperactivity disorder in UK and Turkish samples.
AB  - Molecular genetic studies in attention deficit hyperactivity disorder (ADHD) have
      focussed on candidate genes within the dopamine system, which is thought to be
      the main site of action of stimulant drugs, the primary pharmacological treatment
      of the disorder. Of particular interest are findings with the dopamine
      transporter gene (DAT1), since stimulant drugs interact directly with the
      transporter protein. To date, there have been eight published association studies
      of ADHD with a 480 base-pair allele of a variable number tandem repeat (VNTR)
      polymorphism in the 3'-untranslated region of the gene, five that support an
      association and three against. We have analysed the same VNTR marker in a dataset
      of UK Caucasian children and an independent dataset of Turkish Caucasian children
      with DSM-IV ADHD, using the transmission disequilibrium test (TDT). Results from
      the UK (chi(2) = 8.97, P = 0.001, OR = 1.95), but not the Turkish sample (chi(2)
      = 0.93, P = 0.34) support association and linkage between genetic variation at
      the DAT1 locus and ADHD. When considered alongside evidence from other published
      reports, there is only modest evidence for the association, consistent with a
      very small main effect for the 480-bp allele (chi(2) = 3.45, P = 0.06, OR =
      1.15), however we find significant evidence of heterogeneity between the combined
      dataset (chi(2) = 22.64, df = 8, P = 0.004).

PMID- 11443528
TI  - Two dopamine genes related to reports of childhood retrospective inattention and
      conduct disorder symptoms.
AB  - The 7-repeat allele of the dopamine receptor D4 gene (DRD4) and the 10 repeat
      allele of the dopamine transporter gene (DAT1) have shown association and linkage
      with symptoms of attention deficit hyperactivity disorder (ADHD) in childhood.
      The parents of ADHD children (clinic group, n = 80 fathers and 107 mothers) and
      control children (control group, n = 42 fathers and 51 mothers) were the focus of
      this study. These parents reported retrospectively on their level of ADHD
      Inattention and Conduct Disorder symptoms in adolescence. In analyses of the
      relation of symptom levels to the DRD4 and DAT1 genotypes, fathers possessing the
      7 repeat DRD4 allele had greater levels of both inattention and conduct disorder
      symptoms. Mothers with the 10/10 genotype had higher levels of inattention
      symptoms. Thus, genetic associations found in children may be replicable in their
      parents.

PMID- 11443529
TI  - Role of the serotonin transporter gene in the behavioral expression of autism.
AB  - The promoter polymorphism of the serotonin transporter gene (HTT, locus SLC6A4)
      is of special interest in autism given the well-replicated platelet
      hyperserotonemia of autism, treatment effects of serotonin reuptake inhibitors,
      and the role of serotonin in limbic functioning and neurodevelopment. Parent
      offspring transmission of the long (l) and short (s) alleles of the
      deletion/insertion polymorphism in the HTT promoter region was examined in
      families of 71 children with autism using the transmission test for linkage
      disequilibrium (TDT). Transmission of HTT promoter alleles did not differ between
      probands with autism and their unaffected siblings. However, allelic transmission
      in probands was dependent upon severity of impairments in the social and
      communication domains, with greater s allele transmission in severely impaired
      individuals and greater l transmission in mild/moderately impaired individuals.
      This relationship between HTT promoter alleles and severity of autistic
      impairment was also seen when ratings of social and communication behaviors were
      compared across genotypes. The data indicate that HTT promoter alleles by
      themselves do not convey risk for autism, but, rather, modify the severity of
      autistic behaviors in the social and communication domains. The results require
      replication and, given the size of the groups and subgroups examined, must be
      considered still preliminary. The results suggest that future research on the
      genetics of autism should carefully assess each of the major behavioral domains
      and seriously consider the possible role of modifying loci.

PMID- 11443530
TI  - Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor
      gene: evidence of association but no linkage in a UK sample.
AB  - Recent studies report association and linkage between attention deficit
      hyperactivity disorder (ADHD) and the 7-repeat allele of a 48 base-pair repeat in
      the dopamine D4 receptor gene (DRD4). We examined the frequency of this allele in
      a sample of probands with DSM-IV ADHD using a case-control design, as well as the
      transmission disequilibrium test (TDT) and haplotype-based haplotype relative
      risk (HHRR) in the subset of probands with DNA available from both parents. One
      hundred and thirty-two ADHD probands were compared with 189 controls (chi(2) =
      6.17, 1 df, P = 0.01, OR = 1.73, 95% CI = 1.11--2.71). A total of 85 complete
      trios were available for within-family tests of association and linkage. Fifty
      two heterozygous parents carrying one copy of the 7-repeat were informative for
      the TDT (29 transmitted vs 23 non-transmitted, chi(2) = 0.69). Analysis of the
      entire sample of 132 probands using TRANSMIT provided no additional evidence for
      excess transmission of the 7-repeat allele (58 transmitted vs 54 non
      transmitted). HHRR gave similar results. We conclude that the case-control
      findings are likely to be falsely positive, resulting from genetic
      stratification. However we can not rule out alternative explanations of low
      statistical power and gene-environment correlation.

PMID- 11443531
TI  - Increased S100B blood levels in unmedicated and treated schizophrenic patients
      are correlated with negative symptomatology.
AB  - S100B, a calcium-binding protein produced by astroglial cells, is a marker of
      astroglial cellular integrity. It has been shown to be increased in acute brain
      damage and neurodegeneration. A recent study showed increased S100B levels in
      medicated acutely psychotic patients with schizophrenia. The study presented here
      included 26 drug-free patients with acute schizophrenia and 26 matched healthy
      controls. S100B blood concentrations were determined using a quantitative
      immunoassay upon admission and after 6 weeks of neuroleptic treatment. The PANSS
      was used to investigate psychopathology. Unmedicated schizophrenic patients
      showed significantly increased S100B levels compared to matched healthy controls.
      After 6 weeks of treatment, 11 patients showed normal S100B levels while in 15
      patients the levels remained increased. These patients showed significantly
      higher PANSS negative scores upon admission and after 6 weeks of treatment.
      Schizophrenic patients display a loss of astroglial integrity which is not caused
      by neuroleptic medication. Continuously increased S100B levels are associated
      with negative symptomatology.

PMID- 11443532
TI  - Further evidence for a bipolar risk gene on chromosome 12q24 suggested by
      investigation of haplotype sharing and allelic association in patients from the
      Faroe Islands.
AB  - A number of studies have strongly suggested a susceptibility locus for bipolar
      affective disorder on chromosome 12q24. The present study investigates for a
      shared chromosomal segment among distantly related patients with bipolar
      affective disorder from the Faroe Islands, using 17 microsatellite markers
      covering 24 cM in the previously suggested region on chromosome 12q24. D12S342
      showed possible allelic association to bipolar affective disorder (P-value using
      CLUMP below 0.01). Increased sharing among cases of two-marker haplotypes were
      suggested at D12S1614--D12S342 (P-values using CLUMP below 0.01), and D12S2075-
      D12S1675 (P-values using CLUMP around 0.001). The region of most interest is
      around 6 cM and bounded by markers D12S1614 and D12S1675 as suggested by the
      interesting two-marker haplotypes. This area contains the minimum interesting
      region between D12S342 and D12S1658 suggested by the previously reported
      haplotypes in the two Danish families with bipolar affective disorder.

PMID- 11443533
TI  - Exon/intron boundaries, novel polymorphisms, and association analysis with
      schizophrenia of the human synaptic vesicle monoamine transporter (SVMT) gene.
AB  - The synaptic vesicular monoamine transporter (SVMT), alternatively vesicular
      monoamine transporter 2 (VMAT2), pumps cytosolic monoamines including dopamine,
      norepinephrine, serotonin, and histamine into synaptic vesicles. Altered
      functions of SVMT have been implicated in the pathogensis of several
      neuropsychiatric diseases. We determined exon/intron boundaries of the human SVMT
      gene and performed mutational analysis for the exonic and neighboring intronic
      regions of the gene. Detected polymorphisms were subject to association analysis
      with schizophrenia in a family-based design. The human SVMT gene consists, of 16
      exons and 15 introns, which is consistent with the murine SVMT gene. When
      mutational analysis was performed by the single strand conformational
      polymorphism (SSCP) analysis, we found two and four single nucleotide
      polymorphisms (SNPs) in exons and neighboring introns, respectively. Neither
      exonic SNP results in an amino acid change. In family-based association analyses
      in a sample of 50 Japanese schizophrenics and their parents, no significant
      association was found for the intronic polymorphisms. Our data suggest that there
      is no common polymorphism in the SVMT gene affecting the primary structure of the
      human SVMT protein. Furthermore, we obtained no evidence for the major effect of
      the novel polymorphisms on susceptibility to schizophrenia.

PMID- 11443534
TI  - Voltage-gated calcium channel gamma 2 subunit gene is not deleted in velo-cardio
      facial syndrome.
AB  - Velo-cardio-facial syndrome (VCFS) has been associated with schizophrenic
      symptoms in some patients and is caused by a deletion of 22q11.21--q11.23. The
      voltage-gated calcium channel (VGCC) gamma 2 subunit is located on chromosome 22
      and is telemeric to the most commonly observed VCFS deletion region but is near a
      putative marker for schizophrenia (D22S278). Metaphase spreads of four controls,
      four patients with VCFS, and one patient with VCFS and schizophrenia were
      evaluated for the VCFS deletion using the VCFS-diagnostic probe, TUPLE 1, and for
      deletion of VGCC gamma 2 subunit gene using probes for that gene's exon 1 and
      exons 3 and 4. All of the VCFS patients had deletion of the TUPLE 1 probe on one
      chromosome of the chromosome 22 pair. None showed deletion of the gamma 2 subunit
      exons studied. The location of the gamma 2 subunit gene at 22q13.1 was confirmed
      by FISH in all cases. This study did not show a deletion of the gamma 2 subunit
      gene as a distinguishing feature of our patient with VCFS and schizophrenia.

PMID- 11443535
TI  - Identification of a compound short tandem repeat stretch in the 5'-upstream
      region of the cholecystokinin gene, and its association with panic disorder but
      not with schizophrenia.
AB  - The cholecystokinin gene (CCK) is thought to play a role in the pathogenesis of
      both panic disorder and schizophrenia. In this study, we have extended the 5'
      upstream sequence of the CCK gene, and identified a compound short tandem repeat
      (STR), located approximately -2.2 to -1.8 kb from the cap site. This STR was
      found to be polymorphic with ten different allele lengths. Case-control studies
      using 73 panic patients, 305 schizophrenics and 252 controls showed a significant
      allelic association with panic disorder (P = 0.025), but not with schizophrenia.
      Dividing the STR alleles into three classes according to length, Long (L), Medium
      (M) and Short (S), produced strong genotypic (MM) (nominal P = 0.0014) and
      allelic (M) (nominal P = 0.0079) associations with panic disorder. screening the
      newly extended promoter region detected not only the previously identified -36c>t
      and -188a>g single nucleotide polymorphisms (SNPs) but a new rare snp, -345g>C.
      Neither of the former two SNPs showed significant association with either panic
      disorder or schizophrenia. Haplotypic distributions of the STR and SNPs -188 and 
      36 were significantly different between panic samples and controls (P = 0.0003).
      These findings suggest that the novel STR or a nearby variant may confer
      susceptibility to the development of panic disorder.

PMID- 11443536
TI  - Brain-derived-neurotrophic-factor (BDNF) stress response in rats bred for learned
      helplessness.
AB  - Stress-induced elevation of glucocorticoids is accompanied by structural changes
      and neuronal damage in certain brain areas. This includes reduced expression of
      brain-derived neurotrophic factor (BDNF) in the hippocampus which can be
      prevented by chronic electroconvulsive seizures and antidepressant drug
      treatment. In the last years we have bred two strains of rats, one which reacts
      with congenital helplessness to stress (cLH), and one which congenitally does not
      acquire helplessness when stressed (cNLH). After being selectively bred for more
      than 40 generations these strains have lost their behavioural plasticity
      including their sensitivity to antidepressant treatment. We show here that in cLH
      rats, acute immobilization stress does not induce a reduction of BDNF expression
      in the hippocampus which is observed in Sprague--Dawley and cNLH rats. All
      animals tested exhibited elevated corticosterone levels when stressed, an
      indication, that in cLH rats regulation of BDNF expression in the hippocampal
      formation is uncoupled from corticosterone increase induced through stress. This
      may explain the lack of adaptive responses in this strain.

PMID- 11443537
TI  - Treatment with interferon-alpha (IFN alpha) of hepatitis C patients induces lower
      serum dipeptidyl peptidase IV activity, which is related to IFN alpha-induced
      depressive and anxiety symptoms and immune activation.
AB  - We have shown that treatment with interleukin-2 (IL-2) or interferon-alpha (IFN
      alpha) may induce depressive symptoms and activation of the cytokine network and
      that IL-2 treatment may diminish serum dipeptidyl pepdidase IV (DPP IV) activity.
      DPP IV (EC 3.4.14.5) is a membrane bound serine protease which catalyzes the
      cleavage of some cytokines and neuroactive peptides which modulate T cell
      activity. The aims of the present study were to examine the effects of IFN alpha
      based immunotherapy on serum DPP IV activity in relation to induction of the
      inflammatory response system. In 18 patients with chronic active hepatitis C, we
      determined the Montgomery and Asberg Rating Scale (MADRS), the Hamilton Anxiety
      Rating Scale (HAM-A), serum DPP IV activity, the kynurenine/tryptophan (K/T)
      quotient, which is an indicator of cytokine (in particular IFN)-induced
      catabolism of tryptophan, and serum interleukin-8 (IL-8) before starting therapy
      and 2, 4, 16 and 24 weeks after immunotherapy with IFN alpha. IFN alpha
      immunotherapy significantly suppressed serum DPP IV 2--4 weeks and 16--24 weeks
      after starting IFN alpha-based immunotherapy. The reduction in serum DPP IV
      activity was more pronounced 16--24 weeks after starting immunotherapy than after
      2--4 weeks. The IFN alpha-induced suppression of serum DPP IV activity was
      significantly correlated to IFN alpha-induced increases in the MADRS and HAM-A
      and increases in the K/T quotient and serum IL-8. In conclusion, long-term
      immunotherapy with IFN alpha suppresses serum DPP IV activity and the
      immunotherapy-induced changes in DPP IV are related to increases in severity of
      depression, anxiety and activation of the inflammatory response system.

PMID- 11443538
TI  - Borna disease virus-specific circulating immune complexes, antigenemia, and free
      antibodies--the key marker triplet determining infection and prevailing in severe
      mood disorders.
AB  - Borna disease virus (BDV), a unique genetically highly conserved RNA virus
      (Bornaviridae; Mononegavirales), preferentially targets neurons of limbic
      structures causing behavioral abnormalities in animals. Markers and virus in
      patients with affective disorders and schizophrenia have raised worldwide
      interest. A persistent infection was suggestive from follow-up studies, but
      inconstant detectability weakened a possible linkage.This study for the first
      time discloses that detection gaps are caused by BDV-specific circulating immune
      complexes (CIC), and their interplay with free antibodies and plasma antigens
      (p40/p24). Screening 3000 sera each from human and equine patients over the past
      4 years by new enzyme immunoassays (EIAs) revealed that BDV-CICs indicate 10
      times higher infection rates (up to 30% in controls, up to 100% in patients) than
      did previous serology. Persistence of high amounts of CICs and plasma antigens
      correlates with severity of depression. Even BDV RNA could be detected in plasma
      samples with strong antigenemia. Our discovery not only explains the course of
      persistent infection, but offers novel easy-to-use diagnostic tools by which new
      insights into BDV-related etiopathogenesis of disease and epidemiology are
      possible.

PMID- 11443539
TI  - Linkage and association studies of prostate cancer susceptibility: evidence for
      linkage at 8p22-23.
AB  - Multiple lines of evidence have implicated the short arm of chromosome 8 as
      harboring genes important in prostate carcinogenesis. Although most of this
      evidence comes from the identification of frequent somatic alterations of 8p loci
      in prostate cancer cells (e.g., loss of heterozygosity), studies have also
      suggested a role for 8p genes in mediation of inherited susceptibility to
      prostate cancer. To further examine this latter possibility, we performed linkage
      analyses, in 159 pedigrees affected by hereditary prostate cancer (HPC), using 24
      markers on the short arm of chromosome 8. In the complete set of families,
      evidence for prostate cancer linkage was found at 8p22-23, with a peak HLOD of
      1.84 (P=.004), and an estimate of the proportion of families linked (alpha) of
      0.14, at D8S1130. In the 79 families with average age at diagnosis >65 years, an
      allele-sharing LOD score of 2.64 (P=.0005) was observed, and six markers spanning
      a distance of 10 cM had LOD scores >2.0. Interestingly, the small number of
      Ashkenazi Jewish pedigrees (n=11) analyzed in this study contributed
      disproportionately to this linkage. Mutation screening in HPC probands and
      association analyses in case subjects (a group that includes HPC probands and
      unrelated case subjects) and unaffected control subjects were carried out for the
      putative prostate cancer-susceptibility gene, PG1, previously localized to the
      8p22-23 region. No statistical differences in the allele, genotype, or haplotype
      frequencies of the SNPs or other sequence variants in the PG1 gene were observed
      between case and control subjects. However, case subjects demonstrated a trend
      toward higher homozygous rates of less-frequent alleles in all three PG1 SNPs,
      and overtransmission of a PG1 variant to case subjects was observed. In summary,
      these results provide evidence for the existence of a prostate cancer
      susceptibility gene at 8p22-23. Evaluation of the PG1 gene and other candidate
      genes in this area appears warranted.

PMID- 11443540
TI  - Global analysis of ATM polymorphism reveals significant functional constraint.
AB  - ATM, the gene that is mutated in ataxia-telangiectasia, is associated with
      cerebellar degeneration, abnormal proliferation of small blood vessels, and
      cancer. These clinically important manifestations have stimulated interest in
      defining the sequence variation in the ATM gene. Therefore, we undertook a
      comprehensive survey of sequence variation in ATM in diverse human populations.
      The protein-encoding exons of the gene (9,168 bp) and the adjacent intron and
      untranslated sequences (14,661 bp) were analyzed in 93 individuals from seven
      major human populations. In addition, the coding sequence was analyzed in one
      chimpanzee, one gorilla, one orangutan, and one Old World monkey. In human ATM,
      88 variant sites were discovered by denaturing high-performance liquid
      chromatography, which is 96%-100% sensitive for detection of DNA sequence
      variation. ATM was compared to 14 other autosomal genes for nucleotide diversity.
      The noncoding regions of ATM had diversity values comparable to other genes, but
      the coding regions had very low diversity, especially in the last 29% of the
      protein sequence. A test of the neutral evolution hypothesis, through use of the
      Hudson/Kreitman/Aguade statistic, revealed that this region of the human ATM gene
      was significantly constrained relative to that of the orangutan, the Old World
      monkey, and the mouse, but not relative to that of the chimpanzee or the gorilla.
      ATM displayed extensive linkage disequilibrium, consistent with suppression of
      meiotic recombination at this locus. Seven haplotypes were defined. Two
      haplotypes accounted for 82% of all chromosomes analyzed in all major
      populations; two others carrying the same D126E missense polymorphism accounted
      for 33% of chromosomes in Africa but were never observed outside of Africa. The
      high frequency of this polymorphism may be due either to a population expansion
      within Africa or to selective pressure.

PMID- 11443541
TI  - Fragile-X carrier screening and the prevalence of premutation and full-mutation
      carriers in Israel.
AB  - Fragile-X syndrome is caused by an unstable CGG trinucleotide repeat in the FMR1
      gene at Xq27. Intermediate alleles (51-200 repeats) can undergo expansion to the
      full mutation on transmission from mother to offspring. To evaluate the
      effectiveness of a fragile-X carrier-screening program, we tested 14,334 Israeli
      women of child-bearing age for fragile-X carrier status between 1992 and 2000.
      These women were either preconceptional or pregnant and had no family history of
      mental retardation. All those found to be carriers of premutation or full
      mutation alleles were offered genetic counseling and also prenatal diagnosis, if
      applicable. We identified 207 carriers of an allele with >50 repeats,
      representing a prevalence of 1:69. There were 127 carriers with >54 repeats,
      representing a prevalence of 1:113. Three asymptomatic women carried the fully
      mutated allele. Among the premutation and full-mutation carriers, 177 prenatal
      diagnoses were performed. Expansion occurred in 30 fetuses, 5 of which had an
      expansion to the full mutation. On the basis of these results, the expected
      number of avoided patients born to women identified as carriers, the cost of the
      test in this study (U.S. $100), and the cost of lifetime care for a mentally
      retarded person (>$350,000), screening was calculated to be cost-effective.
      Because of the high prevalence of fragile-X premutation or full-mutation alleles,
      even in the general population, and because of the cost-effectiveness of the
      program, we recommend that screening to identify female carriers should be
      carried out on a wide scale.

PMID- 11443542
TI  - A transmission/disequilibrium test that allows for genotyping errors in the
      analysis of single-nucleotide polymorphism data.
AB  - The present study assesses the effects of genotyping errors on the type I error
      rate of a particular transmission/disequilibrium test (TDT(std)), which assumes
      that data are errorless, and introduces a new transmission/disequilibrium test
      (TDT(ae)) that allows for random genotyping errors. We evaluate the type I error
      rate and power of the TDT(ae) under a variety of simulations and perform a power
      comparison between the TDT(std) and the TDT(ae), for errorless data. Both the
      TDT(std) and the TDT(ae) statistics are computed as two times a log-likelihood
      difference, and both are asymptotically distributed as chi(2) with 1 df. Genotype
      data for trios are simulated under a null hypothesis and under an alternative
      (power) hypothesis. For each simulation, errors are introduced randomly via a
      computer algorithm with different probabilities (called "allelic error rates").
      The TDT(std) statistic is computed on all trios that show Mendelian consistency,
      whereas the TDT(ae) statistic is computed on all trios. The results indicate that
      TDT(std) shows a significant increase in type I error when applied to data in
      which inconsistent trios are removed. This type I error increases both with an
      increase in sample size and with an increase in the allelic error rates. TDT(ae)
      always maintains correct type I error rates for the simulations considered.
      Factors affecting the power of the TDT(ae) are discussed. Finally, the power of
      TDT(std) is at least that of TDT(ae) for simulations with errorless data. Because
      data are rarely error free, we recommend that researchers use methods, such as
      the TDT(ae), that allow for errors in genotype data.

PMID- 11443543
TI  - The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in
      TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further
      genetic heterogeneity of periodic fevers.
AB  - Mutations in the extracellular domain of the 55-kD tumor-necrosis factor (TNF)
      receptor (TNFRSF1A), a key regulator of inflammation, define a periodic-fever
      syndrome, TRAPS (TNF receptor-associated periodic syndrome [MIM 142680]), which
      is characterized by attacks of fever, sterile peritonitis, arthralgia, myalgia,
      skin rash, and/or conjunctivitis; some patients also develop systemic
      amyloidosis. Elsewhere we have described six disease-associated TNFRSF1A
      mutations, five of which disrupt extracellular cysteines involved in disulfide
      bonds; four other mutations have subsequently been reported. Among 150 additional
      patients with unexplained periodic fevers, we have identified four novel TNFRSF1A
      mutations (H22Y, C33G, S86P, and c.193-14 G-->A), one mutation (C30S) described
      by another group, and two substitutions (P46L and R92Q) present in approximately
      1% of control chromosomes. The increased frequency of P46L and R92Q among
      patients with periodic fever, as well as functional studies of TNFRSF1A, argue
      that these are low-penetrance mutations rather than benign polymorphisms. The
      c.193-14 G-->A mutation creates a splice-acceptor site upstream of exon 3,
      resulting in a transcript encoding four additional extracellular amino acids.
      T50M and c.193-14 G-->A occur at CpG hotspots, and haplotype analysis is
      consistent with recurrent mutations at these sites. In contrast, although R92Q
      also arises at a CpG motif, we identified a common founder chromosome in
      unrelated individuals with this substitution. Genotype-phenotype studies
      identified, as carriers of cysteine mutations, 13 of 14 patients with TRAPS and
      amyloidosis and indicated a lower penetrance of TRAPS symptoms in individuals
      with noncysteine mutations. In two families with dominantly inherited disease and
      in 90 sporadic cases that presented with a compatible clinical history, we have
      not identified any TNFRSF1A mutation, despite comprehensive genomic sequencing of
      all of the exons, therefore suggesting further genetic heterogeneity of the
      periodic-fever syndromes.

PMID- 11443544
TI  - Schizophrenia and affective disorders--cosegregation with a translocation at
      chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300
      findings in a family.
AB  - A family with a (1;11)(q42;q14.3) translocation significantly linked to a
      clinical phenotype that includes schizophrenia and affective disorders is
      described. This translocation generates a LOD score of 3.6 when the disease
      phenotype is restricted to schizophrenia, of 4.5 when the disease phenotype is
      restricted to affective disorders, of 7.1 when relatives with recurrent major
      depression, with bipolar disorder, or with schizophrenia are all classed as
      affected. This evidence for linkage is among the strongest reported for a
      psychiatric disorder. Family members showed no distinctive features by which the
      psychiatric phenotype could be distinguished from unrelated cases of either
      schizophrenia or affective disorders, and no physical, neurological, or
      dysmorphic conditions co-occurred with psychiatric symptoms. Translocation
      carriers and noncarriers had the same mean intelligence quotient. Translocation
      carriers were similar to subjects with schizophrenia and different from
      noncarriers and controls, in showing a significant reduction in the amplitude of
      the P300 event-related potential (ERP). Furthermore, P300 amplitude reduction and
      latency prolongation were measured in some carriers of the translocation who had
      no psychiatric symptoms-a pattern found in other families with multiple members
      with schizophrenia, in which amplitude of and latency of P300 appear to be trait
      markers of risk. The results of karyotypic, clinical, and ERP investigations of
      this family suggest that the recently described genes DISC1 and DISC2, which are
      directly disrupted by the breakpoint on chromosome 1, may have a role in the
      development of a disease phenotype that includes schizophrenia as well as
      unipolar and bipolar affective disorders.

PMID- 11443545
TI  - Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect
      and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy.
AB  - Cerebro-oculo-facio-skeletal (COFS) syndrome is a recessively inherited rapidly
      progressive neurologic disorder leading to brain atrophy, with calcifications,
      cataracts, microcornea, optic atrophy, progressive joint contractures, and growth
      failure. Cockayne syndrome (CS) is a recessively inherited neurodegenerative
      disorder characterized by low to normal birth weight, growth failure, brain
      dysmyelination with calcium deposits, cutaneous photosensitivity, pigmentary
      retinopathy and/or cataracts, and sensorineural hearing loss. Cultured CS cells
      are hypersensitive to UV radiation, because of impaired nucleotide-excision
      repair (NER) of UV-induced damage in actively transcribed DNA, whereas global
      genome NER is unaffected. The abnormalities in CS are caused by mutated CSA or
      CSB genes. Another class of patients with CS symptoms have mutations in the XPB,
      XPD, or XPG genes, which result in UV hypersensitivity as well as defective
      global NER; such patients may concurrently have clinical features of another NER
      syndrome, xeroderma pigmentosum (XP). Clinically observed similarities between
      COFS syndrome and CS have been followed by discoveries of cases of COFS syndrome
      that are associated with mutations in the XPG and CSB genes. Here we report the
      first involvement of the XPD gene in a new case of UV-sensitive COFS syndrome,
      with heterozygous substitutions-a R616W null mutation (previously seen in
      patients in XP complementation group D) and a unique D681N mutation-demonstrating
      that a third gene can be involved in COFS syndrome. We propose that COFS syndrome
      be included within the already known spectrum of NER disorders: XP, CS, and
      trichothiodystrophy. We predict that future patients with COFS syndrome will be
      found to have mutations in the CSA or XPB genes, and we document successful use
      of DNA repair for prenatal diagnosis in triplet and singleton pregnancies at risk
      for COFS syndrome. This result strongly underlines the need for screening of
      patients with COFS syndrome, for either UV sensitivity or DNA-repair
      abnormalities.

PMID- 11443546
TI  - Maternal folate polymorphisms and the etiology of human nondisjunction.
AB  - Attempts to identify genetic contributors to human meiotic nondisjunction have
      met with little, if any, success. Thus, recent reports linking Down syndrome to
      maternal polymorphisms at either of two folate metabolism enzymes,
      methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase
      (MTRR), have generated considerable interest. In the present report, we asked
      whether variation at MTHFR (677C-->T) or MTRR (66A-->G) might be associated with
      human trisomies other than trisomy 21. We analyzed maternal polymorphisms at
      MTHFR and MTRR in 93 cases of sex-chromosome trisomy, 44 cases of trisomy 18, and
      158 cases of autosomal trisomies 2, 7, 10, 13, 14, 15, 16, 18, or 22, and
      compared the distributions of genotypes to those of control populations. We
      observed a significant increase in the MTHFR polymorphism in mothers of trisomy
      18 conceptuses but were unable to identify any other significant associations.
      Overall, our observations suggest that, at least for the sex chromosomes and for
      a combined set of autosomal trisomies, polymorphisms in the folate pathway are
      not a significant contributor to human meiotic nondisjunction.

PMID- 11443547
TI  - Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin
      dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia.
AB  - Classic tetrahydrobiopterin (BH(4)) deficiencies are characterized by
      hyperphenylalaninemia and deficiency of monoamine neurotransmitters. In this
      article, we report two patients with progressive psychomotor retardation,
      dystonia, severe dopamine and serotonin deficiencies (low levels of 5
      hydroxyindoleacetic and homovanillic acids), and abnormal pterin pattern (high
      levels of biopterin and dihydrobiopterin) in cerebrospinal fluid. Furthermore,
      they presented with normal urinary pterins and without hyperphenylalaninemia.
      Investigation of skin fibroblasts revealed inactive sepiapterin reductase (SR),
      the enzyme catalyzing the final two-step reaction in the biosynthesis of BH(4).
      Mutations in the SPR gene were detected in both patients and their family
      members. One patient was homozygous for a TC-->CT dinucleotide exchange,
      predicting a truncated SR (Q119X). The other patient was a compound heterozygote
      for a genomic 5-bp deletion (1397-1401delAGAAC) resulting in abolished SPR-gene
      expression and an A-->G transition leading to an R150G amino acid substitution
      and to inactive SR as confirmed by recombinant expression. The absence of
      hyperphenylalaninemia and the presence of normal urinary pterin metabolites and
      of normal SR-like activity in red blood cells may be explained by alternative
      pathways for the final two-step reaction of BH(4) biosynthesis in peripheral and
      neuronal tissues. We propose that, for the biosynthesis of BH(4) in peripheral
      tissues, SR activity may be substituted by aldose reductase (AR), carbonyl
      reductase (CR), and dihydrofolate reductase, whereas, in the brain, only AR and
      CR are fully present. Thus, autosomal recessive SR deficiency leads to BH(4) and
      to neurotransmitter deficiencies without hyperphenylalaninemia and may not be
      detected by neonatal screening for phenylketonuria.

PMID- 11443548
TI  - Many roads lead to a broken heart: the genetics of dilated cardiomyopathy.

PMID- 11443549
TI  - Expression dynamics of human cytomegalovirus immune evasion genes US3, US6, and
      US11 in the blood of lung transplant recipients.
AB  - Delayed elimination of human cytomegalovirus (HCMV)-infected cells by the host
      immune system may contribute to viral dissemination and pathogenesis of HCMV
      infection. The mRNA expression dynamics of HCMV-encoded immune evasion genes US3,
      US6, and US11 expressed after active HCMV infection were analyzed in blood
      samples of lung transplant recipients by means of quantitative nucleic acid
      sequence-based amplification. The results were compared with the expression
      dynamics of IE1 mRNA and pp67 late mRNA, levels of pp65 antigenemia, and
      antiviral treatment. During acute infection, high levels of US3 and US6 RNA were
      detected before antigenemia, which were detected simultaneously with IE1 RNA.
      US11 RNA was detected simultaneously with antigenemia but before late pp67 RNA.
      These data suggest an active role of viral immune evasion during HCMV infection
      in vivo. Interestingly, immune evasion RNA remained detectable after clinical
      recovery, often independently of IE1 RNA expression, indicating persistent viral
      activity, which may have implications for long-term control of HCMV.

PMID- 11443550
TI  - Human immunodeficiency virus-infected patients receiving highly active
      antiretroviral therapy maintain activated CD8+ T cell subsets as a strong
      adaptive immune response to cytomegalovirus.
AB  - CD8(+) T lymphocyte function specific for human cytomegalovirus (CMV) was
      evaluated in 14 patients infected with human immunodeficiency virus (HIV)
      receiving highly active antiretroviral therapy (HAART) and 26 CMV-seropositive
      donors without HIV infection. Fifty-seven percent of the HIV-infected group had
      CMV-specific cytolytic activity in freshly isolated peripheral blood mononuclear
      cells (PBMC) against targets expressing CMV pp65. Both interferon (IFN)-gamma
      secretion by CD8(+) T cells and the frequency of human leukocyte antigen (HLA)
      tetramer-positive T cells in HLA-A*0201-positive HIV-infected subjects correlated
      with CMV-specific cytolysis. In contrast, PBMC from healthy CMV-seropositive
      donors did not have either measurable CMV-specific cytolysis or secretion of IFN
      gamma without in vitro stimulation. The T helper response to CMV antigens was
      vigorous in healthy CMV-seropositive donors but low in the cohort of HIV-infected
      patients. Potent CD8(+) cytotoxic T lymphocyte responses to CMV in HIV-infected
      patients receiving HAART is the converse of what is found in healthy CMV
      seropositive subjects and may be the predominant adaptive immune response against
      CMV in HIV-infected patients.

PMID- 11443551
TI  - The etiology of community-acquired pneumonia at an urban public hospital:
      influence of human immunodeficiency virus infection and initial severity of
      illness.
AB  - In a prospective study, the etiology of community-acquired pneumonia (CAP) was
      investigated among consecutive patients admitted to an academic, urban public
      hospital in Seattle. The study population was uniquely young, was predominantly
      male, and had high rates of homelessness, cigarette smoking, alcoholism,
      injection drug use, and human immunodeficiency virus (HIV) infection. Leading
      causes of CAP among HIV-negative patients were aspiration, followed by
      Streptococcus pneumoniae, Legionella species, and Mycoplasma pneumoniae. Among
      HIV-positive patients, Pneumocystis carinii, Mycobacterium tuberculosis, S.
      pneumoniae, and M. pneumoniae were the most common etiologic agents. Severe CAP
      was associated with typical bacterial infections and aspiration pneumonia but not
      Legionella infection among HIV-negative patients and with Pseudomonas aeruginosa
      infections among HIV-positive patients. These findings emphasize the need to
      tailor empirical antibiotic therapy according to local patient populations and
      individual risk factors and highlight the importance of recognizing underlying
      HIV infection in patients who are hospitalized with CAP.

PMID- 11443552
TI  - Suburban transmission of Q fever in French Guiana: evidence of a wild reservoir.
AB  - The annual incidence of Q fever in French Guiana was found to have increased in
      1996 and was 37/100,000 population over the last 4 years. Subsequent
      investigations in Cayenne and its suburbs indicated that a wild reservoir of the
      bacteria was responsible for the epidemiologic pattern. A case-control study
      showed that residence near a forest and occupations and activities that result in
      exposure to aerosols of dusts from the soil are risk factors for Q fever. By
      means of time-series analysis, a strong positive correlation between rainfall and
      the incidence of Q fever with a time lag of 1-3 months was found. The spatial
      distribution of the cases showed that transmission occurs widely throughout
      greater Cayenne, which is incompatible with a pinpoint source of contamination.
      Transmission from livestock and dissemination of the bacteria by the wind
      appeared to be unlikely, which strengthens the hypothesis that a wild reservoir
      is responsible for transmission.

PMID- 11443553
TI  - Antibodies to capsular polysaccharides of group B Streptococcus in pregnant
      Canadian women: relationship to colonization status and infection in the neonate.
AB  - In a cohort study of 1207 pregnant women in Alberta, Canada, the serotype
      distributions of vaginal-rectal group B Streptococcus (GBS) isolates were
      compared with all isolates from neonates with invasive GBS disease identified by
      population-based surveillance. Serum concentrations of Ia, Ib, II, III, and V
      capsular polysaccharide (CPS)-specific IgG also were determined, according to
      serotype of the vaginal-rectal colonizing GBS strain. GBS colonization was
      detected in 19.5% (235 of 1207) of women. Serotype III accounted for 20.6% (48 of
      233) of colonizing strains available for typing but for 37% (27 of 73) of
      invasive isolates from neonates (P<.01). Maternal colonization with type III was
      least likely to be associated with moderate concentrations of III CPS-specific
      IgG. Serotype III GBS is more invasive than other serotypes in this population;
      this may be due, at least in part, to poor maternal type III CPS-specific
      antibody response.

PMID- 11443554
TI  - Microbiological and inflammatory factors associated with the development of
      pneumococcal pneumonia.
AB  - Pneumococcal pneumonia still is associated with a high mortality rate, despite
      appropriate antimicrobial therapy. Many gaps remain in the understanding of the
      pathogenesis of this deadly infection. The microbial and inflammatory events that
      characterize survival or death after intranasal inoculation of mice with an
      LD(50) inoculum of Streptococcus pneumoniae were investigated. Survival was
      associated with rapid bacterial clearance and low inflammation (surfactant and
      red blood cells in alveoli), but no neutrophil recruitment or lung tissue injury
      was noted. By contrast, death was preceded by strong bacterial growth that peaked
      48 h after the infection and was associated with gradual increases in pulmonary
      levels of interleukin-6, macrophage inflammatory protein (MIP)-1alpha, MIP-2,
      monocyte chemoattractant protein-1, KC, and neutrophil recruitment. The injection
      of tumor necrosis factor-alpha or the addition of lipopolysaccharide or heat
      killed S. pneumoniae to the inoculum enhanced early host response and survival.
      These observations may help develop appropriate markers of evolution of
      pneumonia, as well as new therapeutic strategies.

PMID- 11443555
TI  - CXC chemokine receptor 2 contributes to host defense in murine urinary tract
      infection.
AB  - CXC chemokines have been implicated in the recruitment of neutrophils to sites of
      infection. To determine the role of CXC chemokines in the host response to
      urinary tract infection (UTI), female mice were treated with an antibody against
      the major CXC chemokine receptor in the mouse, CXCR2, before intravesical
      inoculation with Escherichia coli. Anti-CXCR2 prevented the influx of neutrophils
      in urine and kidneys. The absence of a neutrophil response only temporarily
      impaired the clearance of bacteria from the urinary tract, as indicated by 100-
      and 1000-fold more E. coli colony-forming units in urine and kidneys of anti
      CXCR2-treated mice at 24 h, but not at 48 h, after the infection. UTI induced
      increases in the renal concentrations of the CXCR2 ligands macrophage
      inflammatory protein-2 and KC, which were not influenced by anti-CXCR2
      administration. CXC chemokines play an important role in the development of a
      local inflammatory response to UTI.

PMID- 11443556
TI  - Protective anti-Helicobacter immunity is induced with aluminum hydroxide or
      complete Freund's adjuvant by systemic immunization.
AB  - To determine whether systemic immunization against Helicobacter pylori could be
      achieved with an adjuvant approved for human use, the efficacy of vaccination
      with Helicobacter antigen in combination with aluminum hydroxide (AlOH) was
      evaluated in a murine model of Helicobacter infection. Immunization with antigen
      and AlOH induced interleukin-5-secreting, antigen-specific T cells, and
      immunization with antigen and complete Freund's adjuvant induced interferon-gamma
      secreting, antigen-specific T cells, as determined by ELISPOT assay. Both immune
      responses conferred protection after challenge with either H. pylori or H. felis,
      as confirmed by the complete absence of any bacteria, as assessed by both
      histology and culture of gastric biopsy samples. Protection was antibody
      independent, as demonstrated with antibody-deficient muMT mice (immunoglobulin
      gene knockout mice), and CD4(+) spleen T cells from immunized mice were
      sufficient to transfer protective immunity to otherwise immunodeficient rag1(-/-)
      recipients. These results suggest an alternative and potentially more expeditious
      strategy for development of a human-use H. pylori vaccine.

PMID- 11443557
TI  - Lewis antigen expression by Helicobacter pylori.
AB  - Although Helicobacter pylori express Lewis antigens as a component in the
      lipopolysaccharide, their role in the infectious process is not well understood.
      Lewis antigen expression with growth phase was investigated, as well as the
      distribution of Lewis antigens among isolates from asymptomatic and symptomatic
      individuals. Lewis antigens are expressed by H. pylori in a growth phase
      dependent manner, with the greatest expression occurring in the logarithmic phase
      of growth. As growth proceeds, an increasing amount of Lewis antigens are shed
      into the culture supernatant. Lewis antigen expression among H. pylori isolates
      from asymptomatic individuals is characterized by an absence of type I Lewis
      antigens, a decrease in Le(x) expression, and an increase in nontypeable H.
      pylori, as compared with that among H. pylori isolates from symptomatic patients.
      The data support a role for Lewis antigens in the pathogenesis associated with
      symptomatic H. pylori infection in colonized individuals.

PMID- 11443558
TI  - Patterns and implications of naturally acquired immune responses to environmental
      and tuberculous mycobacterial antigens in northern Malawi.
AB  - Interferon (IFN)-gamma responsiveness to 12 purified protein derivative (PPD) and
      new tuberculin antigens from 9 species of mycobacteria was assessed, using a
      whole blood assay, in 616 young adults living in northern Malawi, where
      Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccination provides no
      protection against pulmonary tuberculosis. The prevalence of IFN-gamma
      responsiveness was highest for PPDs of M. avium, M. intracellulare, and M.
      scrofulaceum (the MAIS complex). Correlations between responsiveness paralleled
      genetic relatedness of the mycobacterial species. A randomized, controlled trial
      was carried out, to assess the increase in IFN-gamma responsiveness to M.
      tuberculosis PPD that can be attributed to M. bovis BCG vaccination. The BCG
      attributable increase in IFN-gamma response to M. tuberculosis PPD was greater
      for individuals with low initial responsiveness to MAIS antigens than for those
      with high initial responsiveness. Although not statistically significant, the
      trend is consistent with the hypothesis that prior exposure to environmental
      mycobacteria interferes with immune responses to BCG vaccination.

PMID- 11443559
TI  - Nitric oxide synthase 2(Lambarene) (G-954C), increased nitric oxide production,
      and protection against malaria.
AB  - A point mutation in the promoter of the nitric oxide synthase 2 gene (NOS2),
      termed NOS2(Lambarene) (NOS2-G954C), protects heterozygous carriers against
      severe malaria as effectively as the sickle cell trait. In a prospective
      longitudinal study, 841 individual infections of initially 200 children (151 wild
      type vs. 49 NOS2(Lambarene) carriers) were monitored for 4 years, to assess the
      rates of malarial attacks in the 2 groups; carriers of the NOS2(Lambarene)
      polymorphism were significantly less likely to experience malarial attacks than
      were others (P=.002). The distribution of the NOS2(Lambarene) polymorphism was
      investigated in malaria-endemic areas. It was found to be present with the
      highest frequency in Africa and at a lower frequency in Asia. Ex vivo studies
      showed that cells isolated from people with this polymorphism have a 7-fold
      higher baseline NOS activity, compared with the levels detected in cells from
      subjects with the wild-type gene (P=.003).

PMID- 11443560
TI  - Host-pathogen interactions: the attributes of virulence.
AB  - Virulence is one of a number of possible outcomes of host-microbe interaction. As
      such, microbial virulence is dependent on host factors, as exemplified by the
      pathogenicity of avirulent microbes in immunocompromised hosts and the lack of
      pathogenicity of virulent pathogens in immune hosts. Pathogen-centered views of
      virulence assert that pathogens are distinguished from nonpathogens by their
      expression of virulence factors. Although this concept appears to apply to
      certain microbes that cause disease in normal hosts, it does not apply to most
      microbes that cause disease primarily in immunocompromised hosts. The study of
      virulence is fraught with the paradox that virulence, despite being a microbial
      characteristic, can only be expressed in a susceptible host. Thus, the question
      "What is a pathogen?" begs the question, "What is the outcome of the host-microbe
      interaction?" We propose that host damage provides a common denominator that
      translates into the different outcomes of host-microbe interaction.

PMID- 11443561
TI  - Lassa fever encephalopathy: Lassa virus in cerebrospinal fluid but not in serum.
AB  - The pathogenesis of neurologic complications of Lassa fever is poorly understood.
      A Nigerian patient had fever, disorientation, seizures, and blood-brain barrier
      dysfunction, and Lassa virus was found in cerebrospinal fluid (CSF) but not in
      serum. The concentration of Lassa virus RNA in CSF corresponded to 1 x 10(3)
      pfu/mL, as determined by a quantitative real-time polymerase chain reaction
      assay. To characterize the Lassa virus in CSF, the 3.5-kb S RNA was sequenced. In
      the S RNA coding sequences, the CSF strain differed between 20% and 24.6% from
      all known prototype strains. These data suggest that Lassa virus or specific
      Lassa virus strains can persist in the central nervous system and thus contribute
      to neuropathogenesis. Lassa virus infection should be considered in West African
      patients or in travelers returning from this area who present only with fever and
      neurologic signs.

PMID- 11443562
TI  - Phase 1 evaluation of the respiratory syncytial virus-specific monoclonal
      antibody palivizumab in recipients of hematopoietic stem cell transplants.
AB  - Intravenous palivizumab (15 mg/kg) was investigated in 2 phase 1 studies among
      recipients of hematopoietic stem cell transplants (HSCTs). Study 1 included 6
      HSCT patients without active respiratory syncytial virus (RSV) infection. Study 2
      included 15 HSCT patients with RSV upper respiratory tract infection (URTI; n=3)
      or RSV interstitial pneumonia (IP; n=12), all of whom also received aerosolized
      ribavirin. Peak serum concentrations of palivizumab in the 2 studies were
      similar. The mean serum half-life was 22.4 days in study 1, which mainly included
      autologous HSCT recipients, and 10.7 days in study 2, which mainly included
      allogeneic HSCT recipients. No antibodies to palivizumab were detected in study
      1. No adverse events were attributed to palivizumab in the 2 studies. In study 2,
      all 3 patients with RSV URTI recovered without progression to lower respiratory
      tract disease, and 10 (83%) of the 12 patients with RSV IP survived the 28-day
      study period. Thus, palivizumab appears to be safe and well tolerated in HSCT
      recipients.

PMID- 11443563
TI  - Local interferon-gamma levels during respiratory syncytial virus lower
      respiratory tract infection are associated with disease severity.
AB  - To investigate the role of cell-mediated immunity during respiratory syncytial
      virus (RSV) infection, interferon (IFN)-gamma and interleukin (IL)-10 levels in
      nasopharyngeal secretions were measured in infants with lower respiratory tract
      infection (LRTI) caused by RSV. A novel technique was used to measure in vivo
      cytokine levels in nasopharyngeal aspirates (NPAs). Cytokine levels in the NPAs
      of 17 mechanically ventilated infants and 43 nonventilated hospitalized infants
      were compared. As expected, mechanically ventilated infants were significantly
      younger than nonventilated infants (7 vs. 14 weeks). IFN-gamma levels were above
      the limit of detection in the NPAs of 3 (18%) mechanically ventilated infants and
      in the NPAs of 26 (60%) nonventilated infants. IL-10 levels in the NPAs of
      mechanically ventilated and nonventilated infants were comparable. It is
      hypothesized that maturation-related mechanisms have a key role in the
      development of RSV LRTI that results in mechanical ventilation.

PMID- 11443564
TI  - Sexual transmission risk among noninjecting heroin users infected with human
      immunodeficiency virus or hepatitis C virus.
AB  - To assess whether human immunodeficiency virus (HIV)-infected and/or hepatitis C
      virus (HCV)-infected noninjecting heroin users (NIUs) are a potential sexual
      transmission bridge to "lower risk" partners, 180 HIV- or HCV-infected NIUs
      recruited in New York City were interviewed about their sexual behaviors and
      partnerships. Sixty-two percent were former injecting drug users (IDUs). Partners
      reported not to be HIV infected, IDUs, or men who have sex with men were defined
      as lower risk. Among 54 HIV-infected NIUs, lower risk partners were reported by
      54% of never IDUs and 23% of former IDUs (P=.02). Among 155 HCV-infected NIUs,
      lower risk partners were reported by 54% of never IDUs and 45% of former IDUs
      (not significant). Engaging in unprotected vaginal or anal sex and having lower
      risk partners was reported by 29% of HIV-infected never IDUs, 12% of HIV-infected
      former IDUs, 29% of HCV-infected never IDUs, and 34% of HCV-infected former IDUs.
      HIV-infected NIUs, particularly never IDUs, and, possibly, HCV-infected NIUs, are
      a potential sexual transmission bridge.

PMID- 11443565
TI  - Trends in human immunodeficiency virus type 1 (HIV-1) load among HIV-1-infected
      children with hemophilia.
AB  - In human immunodeficiency virus type 1 (HIV-1)-infected persons, virus load
      (serum/plasma level of HIV) predicts outcome. Virus load trends have been
      characterized in adults and infants but not in children. Virus load trends in 22
      male children with hemophilia who acquired HIV-1 postnatally (age 0.7-5.2 years
      at seroconversion) were studied. The mean HIV-1 load 2 years after seroconversion
      was 4.40 log10 copies/mL, and the mean change over time (slope) was 0.03 log10
      copies/(mL x year). Significant among-children variation was apparent: a random
      effects model predicted that 95% of children had early virus loads 3.75-5.04
      log10 copies/mL and slopes -0.07 to 0.12 log10 copies/(mL x year). Higher early
      virus loads and higher slopes were each associated with increased mortality
      (P=.006 and P=.03, respectively). In conclusion, those subjects had virus load
      trends similar to those in adults. Early virus loads were lower than those in
      vertically infected infants, which suggests that factors changing soon after
      birth affect viral replication.

PMID- 11443566
TI  - Nosocomial outbreak of multiple bloodborne viral infections.
AB  - In resource-limited countries, nosocomial transmission of bloodborne pathogens is
      a major public health concern. After a major outbreak of human immunodeficiency
      virus (HIV) infection in approximately 400 children in 1998 in Libya, we tested
      HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) markers in 148 children
      and collected epidemiological data in a subgroup of 37 children and 46 parents.
      HIV infection was detected in all children but one, with HCV or HBV coinfection
      in 47% and 33%, respectively. Vertical transmission was ruled out by analysis of
      parents' serology. The children visited the same hospital 1-6 times; at each
      visit, invasive procedures with potential blood transmission of virus were
      performed. HIV and HCV genotypic analyses identified a HIV monophyletic group,
      whereas 4 clusters of HCV sequences were identified. To our knowledge, this is
      the largest documented outbreak of nosocomial HIV transmission.

PMID- 11443567
TI  - Effects of anti-inflammatory agents on serum levels of calcitonin precursors
      during human experimental endotoxemia.
AB  - Calcitonin precursor (CTpr) levels are both markers and mediators of
      inflammation. The duration of their elevation after intravenous endotoxin
      challenge and the effects of anti-inflammatory therapies were studied in 52
      subjects. CTpr levels maximized at 24 h in all subjects. At 7 days (n=4), after
      levels of acute-phase cytokines and C-reactive protein had normalized, CTpr
      levels remained 2-4-fold above baseline levels. The elimination half-life of CTpr
      levels ranged from 26.9 to 45.7 h. At 24 h, endotoxin and ibuprofen (compared
      with endotoxin alone) increased CTpr levels approximately 2-fold (P=.03), whereas
      soluble tumor necrosis factor receptor blunted the increase in CTpr levels by 2-3
      fold (P=.0015). However, soluble interleukin-1 receptor failed to alter the
      increase in CTpr levels. Thus, the fact that anti-inflammatory agents may alter
      CTpr levels resulting from a single stimulus must be considered when CTpr is used
      as a clinical marker. Of importance, this study reveals that anti-inflammatory
      agents may modulate the CTpr level, which is a potential toxic mediator of
      inflammation.

PMID- 11443568
TI  - Influence of prior meningococcal C polysaccharide vaccination on the response and
      generation of memory after meningococcal C conjugate vaccination in young
      children.
AB  - To determine whether the immunological hyporesponsiveness induced by
      meningococcal AC polysaccharide (MACP) vaccines can be overcome by meningococcal
      C conjugate (MCC) vaccine in young children, serum bactericidal antibody (SBA)
      serogroup C-specific IgG and IgG avidity indices were measured in young children
      who received MACP vaccine, followed 7 months later by MCC vaccine, and their
      responses were compared with those in age-matched MACP-naive control children,
      who received a single dose of MCC vaccine. For children <1 year of age at MACP
      vaccination, the SBA geometric mean titer (GMT) after MCC vaccination was lower
      (P=.022) and proportions with SBA titers <8 (P=.0083) or <128 (P=.0091) were
      higher than those in the control children. For older children, there was no
      difference in the SBA GMTs between the study and control groups (P>.5) or in the
      proportion with SBA titers <8 (P=1.00) or <128 (P=.98). No increase in avidity
      occurred after MACP vaccination, whereas avidity increased significantly 1 month
      after MCC vaccination, with a further increase at 6 months, which indicates that
      the induction of immunological memory was not impaired.

PMID- 11443569
TI  - Treatment of diarrhea caused by Giardia intestinalis and Entamoeba histolytica or
      E. dispar: a randomized, double-blind, placebo-controlled study of nitazoxanide.
AB  - A prospective randomized, double-blind, placebo-controlled study was conducted to
      assess the efficacy and safety of nitazoxanide in the treatment of diarrhea
      caused by Giardia intestinalis or Entamoeba histolytica and/or E. dispar in 89
      adults and adolescents, 22 of whom were diagnosed with G. intestinalis, 53 with
      E. histolytica and/or E. dispar, and 14 with both G. intestinalis and E.
      histolytica and/or E. dispar. The study medication was administered as 1
      nitazoxanide 500-mg tablet or a matching placebo twice daily for 3 days. Thirty
      eight (81%) of 47 patients in the nitazoxanide treatment group resolved diarrhea
      within 7 days (median, 3 days) after initiation of treatment, versus 17 (40%) of
      42 in the placebo group (P=.0002). With its efficacy in treating a broad spectrum
      of enteric protozoan pathogens, nitazoxanide could play an important role in the
      management of diarrhea caused by enteric protozoa, reducing morbidity and costs
      associated with these diarrheal illnesses.

PMID- 11443570
TI  - Detection of serum IgG antibodies specific for Wolbachia surface protein in
      rhesus monkeys infected with Brugia malayi.
AB  - The mechanism of lymphedema development in individuals with lymphatic filariasis
      is presently poorly understood. To investigate whether Wolbachia, symbiotic
      bacteria living within filarial nematodes, may be involved in disease
      progression, Wolbachia-specific immune responses were assayed in a group of
      Brugia malayi-infected rhesus monkeys. Serum IgG antibodies specific for a major
      Wolbachia surface protein (WSP) were detected in 2 of 12 infected monkeys. It is
      interesting that both of these monkeys developed lymphedema after becoming
      amicrofilaremic. WSP-specific antibody responses were temporally associated with
      increases in antifilarial IgG1 antibodies as well as lymphedema development.
      These findings suggest that Wolbachia may be important in understanding disease
      caused by filarial worms.

PMID- 11443571
TI  - Hepatitis A virus infection and atherosclerosis.

PMID- 11443573
TI  - mTOR inhibitors: an overview.
AB  - Inhibitors of the mammalian target of rapamycin are a new class of
      immunosuppressants. In contrast to other macrolides, such as tacrolimus and
      cyclosporine A, they do not inhibit calcineurin and thus signal I of T-cell
      activation. By inhibiting signal III, the mechanism of action and side effects of
      sirolimus (rapamycin) and its derivative RAD are distinct from other
      immunosuppressants. Reports of synergism with cyclosporine A and tacrolimus in
      preclinical and clinical studies, avoidance of nephrotoxicity, and possible
      treatment or prevention of chronic allograft rejection are leading to high
      expectations for this new class of immunosuppressants. Furthermore, studies
      evaluating tolerance induction are being conducted. This review summarizes
      preclinical and clinical results published to date and exploits the future value
      of sirolimus and RAD for clinical transplantation.

PMID- 11443574
TI  - Right hepatic lobe donation for living donor liver transplantation: impact on
      donor quality of life.
AB  - Adult right hepatic lobe living donor liver transplantation (LDLT) has rapidly
      gained widespread acceptance as an effective procedure for selected patients with
      end-stage liver disease. However, there are currently no published data on the
      effect of this procedure on the quality of life of donors. We report the results
      of a survey of our living liver transplant donors to determine the effect of
      right hepatic lobe donation on quality of life. We have performed 30 LDLTs since
      1997; 24 of these have a follow-up of 4 months or longer. In August 2000, these
      patients were sent a questionnaire (including a Medical Outcomes Study 36-Item
      Short-Form Survey) regarding psychosocial outcomes and symptoms after surgery.
      Major complications occurred in 4 of 24 patients (16%), and minor complications,
      in 4 of 24 patients (16%). Complete recovery occurred in 75% of patients at a
      mean time of 3.4 months. Ninety-six percent of patients returned to the same
      predonation job after a mean time of 2.4 months, and 66% of patients required a
      period of light-duty work for a mean of 2.8 months before returning to full-duty
      work. A change in body image was reported in 42% of patients, and 71% reported
      mild ongoing symptoms (primarily abdominal discomfort) that they related to the
      donor surgery for which 29% sought evaluation by a physician. The donor's
      relationship with the recipient was the same or better in 96% of donors, and the
      relationship with the donor's significant other was the same or better in 88% of
      donors. Mean out-of-pocket expenses incurred by donors were $3,660. Sixty-three
      percent of donors reported experiencing more pain than anticipated. All patients
      would donate again if necessary, and 96% benefited from the donor experience. In
      conclusion, (1) all our donors are alive and well after donation; (2) almost all
      donors were able to return to predonation employment status within a few months;
      (3) most donors have mild persistent abdominal symptoms, and some donors had a
      change in body image that they attribute to the donor surgery; and (4) this
      information should be provided to potential donors so they may better understand
      the impact of donor surgery.

PMID- 11443575
TI  - Proceed with caution: live living donation of lobes of liver for transplantation.

PMID- 11443576
TI  - Clinical validation of an artificial neural network trained to identify acute
      allograft rejection in liver transplant recipients.
AB  - Artificial neural networks (ANNs) are techniques of nonlinear data modeling that
      have been studied in a wide variety of medical applications. An ANN was developed
      to assist in the diagnosis of acute rejection in liver transplant recipients. We
      investigated the diagnostic accuracy of this ANN on a new data set of patients
      from the same hospital. In addition, we compared the diagnostic accuracy of the
      ANN with that of the individual input variables (alanine aminotransferase [ALT]
      and bilirubin levels and day posttransplantation). Clinical and biochemical data
      were collected retrospectively for 124 consecutive liver transplantations (117
      patients) over the first 3 months after transplantation. Diagnostic accuracy was
      calculated using receiver operating characteristic (ROC) curve analysis. The ANN
      differentiated rejection from rejection-free episodes in the new data set over
      the first 3 months posttransplantation with an area under the ROC curve of 0.902
      and sensitivity and specificity of 80.0% and 90.1% at the optimum decision
      threshold, respectively. The ANN was significantly more specific than ALT or
      bilirubin level or day posttransplantation at their corresponding optimum
      decision thresholds (P <.0001). Peak ANN output occurred 1 day earlier than peak
      values for either ALT or bilirubin (P <.005). The diagnostic accuracy of the ANN
      was greater than that of any of the individual variables that had been used as
      inputs. It would be a useful adjunct to conventional liver function tests for
      monitoring liver transplant recipients in the early postoperative period.

PMID- 11443577
TI  - A multicenter study of lamivudine treatment in 33 patients with hepatitis B after
      liver transplantation.
AB  - Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to
      severe and rapidly progressive graft failure. Antiviral treatment may be of
      benefit in selected patients with recurrent hepatitis B post-LT. The aim of this
      prospective open-label study is to determine the safety and efficacy of
      lamivudine in 33 liver transplant recipients with active HBV infection. The
      median time from LT to study enrollment was 51 months, all patients were
      hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable
      hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median
      duration of lamivudine treatment on study was 85 weeks, during which time median
      HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously
      detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most
      patients and normalized in 27% of patients with elevated values pretreatment.
      Serum bilirubin and albumin levels significantly improved in patients with
      abnormal values at entry (P <.05). Virological breakthrough was detected in 13
      subjects after a median of 61 weeks of lamivudine treatment and was confirmed to
      be caused by YMDD mutants in all patients tested. None of the patients with
      virological breakthrough showed a complete loss of clinical response to
      lamivudine. Serum ALT and bilirubin levels in patients with and without
      virological breakthrough were not significantly different at last study follow
      up. Study results show that lamivudine is safe and effective in liver transplant
      recipients with recurrent hepatitis B. However, the high rate of virological
      breakthrough with prolonged therapy indicates the need for further studies of
      combination antiviral therapy in this patient population. Our results and others
      further establish the improving long-term outcomes with LT for patients with
      hepatitis B through advances in prevention of reinfection, as well as the
      availability of safe and effective antiviral therapies to treat patients with HBV
      recurrence.

PMID- 11443578
TI  - Lamivudine for hepatitis B after liver transplantation.

PMID- 11443579
TI  - Transmission of hepatitis B infection from hepatitis B core antibody--positive
      liver allografts is prevented by lamivudine therapy.
AB  - Donor shortage has led to the use of hepatitis B core antibody (anti-HBc)-
      positive (anti-HBc(+)) liver allografts for patients in need of relatively urgent
      orthotopic liver transplantation (OLT). Because anti-HBc(+) allografts transmit
      hepatitis B virus (HBV) infection at a high rate, effective prophylaxis is
      required. We assessed the effectiveness of lamivudine in preventing HBV
      transmission by anti-HBc(+) allografts. Between March 1996 and March 2000 at
      Cedars-Sinai Medical Center (Los Angeles, CA), 15 of 169 patients (8.9%) received
      liver allografts from anti-HBc(+) donors. Six patients were hepatitis B surface
      antigen (HBsAg)(+) (group 1), and 9 patients were HBsAg negative (HBsAg(-); group
      2) before OLT. All patients were administered lamivudine, 100 or 150 mg/d, orally
      after OLT. Patients who were HBsAg(+) before OLT also were administered hepatitis
      B immunoglobulin (HBIG) prophylaxis. Hepatitis B serological tests were performed
      on all patients, and HBV DNA was determined in liver tissues in 10 patients. All
      15 patients remained HBsAg(-) at their last follow-up 2 to 40 months (mean, 17
      months) post-OLT. All patients in group 1 had antibody to HBsAg (anti-HBs) titers
      greater than 250 mIU/mL post-OLT (mean follow-up, 20 months; range, 7 to 40
      months). Of the 2 patients in group 1 who underwent liver biopsy after OLT, 1
      patient had detectable hepatic HBV DNA despite being anti-HBs(+) and HBsAg(-).
      Among the patients in group 2, none acquired anti-HBc or HBsAg. Hepatic HBV DNA
      was undetectable in the 7 patients in group 2 who underwent liver biopsy after
      OLT. Anti-HBc(+) allografts can be safely used in patients who undergo OLT for
      chronic hepatitis B and susceptible transplant recipients if prophylaxis with
      combination HBIG and lamivudine or lamividine alone is administered after OLT,
      respectively. However, more data are needed to determine the efficacy of
      lamivudine monotherapy in preventing transmission of HBV infection from anti
      HBc(+) liver allografts to susceptible recipients.

PMID- 11443580
TI  - Transmission of hepatitis B infection from hepatitis B core antibody--positive
      livers: background and prevention.

PMID- 11443581
TI  - A cross-sectional study of SEN virus in liver transplant recipients.
AB  - A new DNA virus, referred to as SEN virus (SEN V), has been isolated and is
      associated with blood-product transfusion and possibly Non A to Non E hepatitis.
      We performed a cross-sectional analysis of SEN V in liver transplant recipients
      at our center. Polymerase chain reaction was used to test for 2 genotypes of SEN
      V (SEN V:C/H and SEN V:D) in 58 unselected patients. Comparisons were made
      between SEN V--positive and SEN V--negative groups in terms of age, time
      posttransplantation, indications for transplantation, serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and
      cytomegalovirus and Epstein-Barr virus status. Thirty of 58 transplant recipients
      (51.7%) were SEN V positive; 15.5% were positive for SEN V:C/H, 24.1% for SEN:D,
      and 12.1% for both strains. No significant differences were found based on
      primary indication for transplantation, including hepatitis C virus (HCV). Of the
      14 of 21 patients with HCV seropositivity and HCV reinfection, 79% were positive
      for SEN V (P =.02). There was no difference in the proportion of patients with
      abnormal serum ALT and/or AST levels. A trend for the SEN V--positive group to
      have a greater mean ALT level (82 v 41 U/L; P =.067) was attributable to the
      subgroup with HCV recurrence because there was no difference in mean ALT levels
      (34.9 v 34.5 U/L; P =.968) in non--HCV-infected transplant recipients. Even in
      the subgroup (n = 14) with recurrent HCV, there was no statistically significant
      difference in mean ALT levels (140 v 105 U/L; P =.665). Age and cytomegalovirus
      or Epstein-Barr virus status were not significantly different between the 2
      groups, but a significant difference in posttransplantation time was noted (16.8
      v 32 months; P =.021). We conclude that SEN V is common among liver transplant
      recipients but does not appear to cause graft dysfunction as an isolated agent.
      There is a suggestion that SEN V may be associated with HCV recurrence, but we
      did not detect biochemical differences attributable to SEN V.

PMID- 11443582
TI  - Effects of prostaglandin E(1) on the efficacy of xenogeneic extracorporeal pig
      liver perfusion in a canine model of acute liver failure.
AB  - Xenogeneic extracorporeal liver perfusion (ECLP) has the potential to become an
      important tool in the management of patients with severe liver failure. We
      previously showed that xenogeneic pig liver perfusion may be prolonged for up to
      9 hours by the administration of prostaglandin E(1) (PGE(1)). In this study, we
      used a canine model of acute liver failure to evaluate the effects of PGE(1) on
      the efficacy of ECLP as a liver-assist device. Liver failure was surgically
      induced in 12 beagle dogs, with a control group (group 1, n = 4) not connected to
      the ECLP circuit. Direct cross-circulation between the dogs and the ECLP circuit
      using a pig liver was performed without (group 2, n = 4) or with (group 3, n = 4)
      continuous administration of PGE(1) through the portal vein of the pig liver. The
      duration of cross-circulation in group 3 (9.4 +/- 1.2 hours) was significantly
      longer than in group 2 (4.3 +/- 1.0 hours). In addition, elevation of blood
      ammonia, total bile acid, and hyaluronic acid levels was less marked in group 3
      compared with the other 2 groups. The ratio of branched-chain amino acids to
      aromatic amino acids was also improved in group 3. The mean survival time in
      group 3 (26.6 +/- 0.4 hours) was significantly longer than in group 1 (15.5 +/-
      1.3 hours) or group 2 (17.1 +/- 2.9 hours). Continuous administration of PGE(1)
      to xenogeneic ECLP resulted in a significant improvement in both liver function
      and survival time of dogs with surgically induced liver failure.

PMID- 11443583
TI  - Beneficial effects of converting liver transplant recipients from cyclosporine to
      tacrolimus on blood pressure, serum lipids, and weight.
AB  - Hypertension and hyperlipidemia are more prevalent after liver transplantation
      with cyclosporine as the primary immunosuppressive agent compared with
      tacrolimus. To determine whether blood pressure, serum lipid level, or weight
      improves when patients switch immunosuppression therapy, we retrospectively
      studied 26 liver transplant recipients with stable graft function who had been
      converted from cyclosporine to tacrolimus therapy with a median follow-up of 8
      months. One of the 26 patients developed pruritus necessitating withdrawal of
      tacrolimus. The results therefore concern the remaining 25 patients. With the
      exception of a small decrease in bilirubin level (P <.05), there was no
      difference in graft or renal function after conversion. Mean systolic blood
      pressure decreased from 158 +/- 25 to 148 +/- 22 mm Hg over a mean of 8 +/- 3
      months after conversion to tacrolimus (P =.015), whereas mean serum cholesterol
      level decreased from 5.3 +/- 0.9 to 4.9 +/- 0.9 mmol/L (P =.01). Sixty-eight
      percent of the patients lost weight, from a mean of 79.4 +/- 22.6 to 76.1 +/-
      20.1 kg, in the 11 months after switching to tacrolimus therapy (P =.024). Serum
      triglyceride and blood glucose levels did not change, and no patient developed
      diabetes mellitus after conversion. These results indicate that switching from
      cyclosporine to tacrolimus can reduce blood pressure, serum cholesterol level,
      and weight after liver transplantation.

PMID- 11443584
TI  - Type of donor aortic preservation solution and not cold ischemia time is a major
      determinant of biliary strictures after liver transplantation.
AB  - The development of biliary strictures (BSs) after liver transplantation (LT)
      continues to affect 10% to 30% of patients, causing substantial morbidity. The
      cause of BSs is multifactorial, including technical, immune, and, in particular,
      ischemic factors. The importance of adequate flushing of the peribiliary arterial
      tree has been stressed. We hypothesized that high-viscosity (HV) preservation
      solutions in the donor do not completely flush the small donor peribiliary
      plexus, leading to inadequate preservation of the bile ducts and posttransplant
      BSs. To test this hypothesis, we retrospectively compared the incidence of BSs in
      2 groups of adults undergoing LT using different types of aortic preservation
      solution in the donor: group 1 (n = 24), low-viscosity (LV) Marshall solution;
      and group 2 (n = 27), HV University of Wisconsin (UW) solution. All donors in
      both groups received additional portal flushes with UW. All LTs were performed
      between November 1995 and August 1998 at 2 centers by the same surgeon,
      eliminating a technical bias. Terminal duct-to-duct anastomosis was performed in
      all recipients except 1 patient in group 1, who underwent a bile duct-to-jejunum
      anastomosis. BSs were first suspected on clinical and biochemical grounds and
      then confirmed by endoscopic retrograde cholangiopancreatography. Identical
      medical protocols were used in all patients. One-year patient survival rates in
      groups 1 and 2 were 92% and 100%, respectively (P =.9). One-year graft survival
      was identical to patient survival. The incidence of BSs in group 1 was 4.1% (1 of
      24 patients), compared to 29.7% in group 2 (8 of 27 patients; P =.02). The BS in
      group 1 occurred 4 months post-LT and was anastomotic. BSs in group 2 occurred
      between 1 and 12 months post-LT and were anastomotic, extrahepatic, intrahepatic,
      or combined intrahepatic and extrahepatic. There were no significant differences
      in the following factors between groups 1 and 2: donor age, local versus imported
      liver, split-liver or full-liver transplantation, incidence of multiple vessels
      in the donor liver, indications for LT, recipient age, T-tube versus no T-tube,
      post-LT peak aspartate aminotransferase level, and treatment for rejection. There
      was no hepatic artery thrombosis or primary nonfunction in either group.
      Interestingly, cold ischemia time (CIT) was longer in group 1, which had the
      least incidence of BSs (692 +/- 190 v 535 +/- 129 minutes in group 2; P =.001).
      Follow-up was longer in group 1 (28.9 +/- 8.3 v 15.6 +/- 8 months in group 2; P
      =.0001). Preservation costs per procurement were 1.9 times greater in the UW
      group than in the Marshall group. Donor aortic flushing with an HV preservation
      solution leads to more frequent BSs compared with an LV preservation solution.
      The impact of preservation solution outweighs the previously described
      deleterious impact of prolonged CIT. Mixed preservation solution (Marshall
      solution in the aorta, UW solution in the portal vein) might protect against BS
      formation while providing optimal liver graft preservation, function, and
      survival despite a mean CIT longer than 10 hours.

PMID- 11443585
TI  - Images of deadly fungal infections after liver transplantation.

PMID- 11443586
TI  - Use of intraoperative Doppler ultrasound to diagnose hepatic venous obstruction
      in a right lobe living donor liver transplant.
AB  - Right lobe liver transplantation is a relatively new and technically challenging
      method of living donor transplantation. Integrity of the hepatic venous
      anastomosis is crucial for successful transplantation. We describe the use of
      intraoperative Doppler sonography to diagnose stenosis of the hepatic vein
      anastomosis, with associated compromise of venous drainage and graft perfusion.

PMID- 11443587
TI  - Technical challenges of hepatic venous outflow reconstruction in right lobe adult
      living donor liver transplantation.
AB  - A right lobe graft that is drained by the right hepatic vein (RHV) is obtained by
      transecting the liver on the right side of the middle hepatic vein (MHV). On
      occasion, a small RHV that only drains a portion of the right lobe, with the
      predominant outflow achieved by the MHV, is encountered. If such variation is not
      recognized while performing right lobe liver transplantation and the RHV only is
      used for reconstruction, venous outflow obstruction with subsequent graft
      congestion and eventual graft failure will occur. Additionally, preservation of
      the main MHV and its branch drainage of the left lobe is crucial to avoid outflow
      blockage to the remaining segment 4 in the donor. We report 4 cases showing a
      variant type of small RHV and large MHV branch that drain not only segments 5 and
      8, but also segments 6 and 7. These variations were simultaneously associated
      with a large-caliber inferior RHV that also required reconstruction. The methods
      used to diagnose such anatomic variations and the techniques for reconstruction
      in the donor and recipient are described.

PMID- 11443588
TI  - Successful tacrolimus therapy for a severe recurrence of type 1 autoimmune
      hepatitis in a liver graft recipient.
AB  - A 34-year-old woman underwent orthotopic liver transplantation (OLT) for
      decompensated type 1 autoimmune hepatitis (AIH). She was administered standard
      triple-drug immunosuppressive therapy (cyclosporine, steroids, and azathioprine).
      Ten years after OLT, she developed a recurrence of AIH, with emergence of
      serological markers of autoimmunity (high anti--smooth muscle antibody [ASMA]
      titer, high serum gamma globulin level), abnormal liver function test results,
      and characteristic histological features on liver biopsy. Despite intensified
      steroid therapy, her clinical and liver function deteriorated. The onset of
      cutaneous alternariosis led to a steroid dose reduction and cyclosporine
      replacement by tacrolimus. Clear-cut amelioration was observed, with an
      improvement in liver function test results and reduction in ASMA titer. One year
      after the recurrence of AIH, the patient has normal liver function and physical
      findings. Tacrolimus therefore may be effective in patients with severe recurrent
      autoimmune liver disease. Further studies are needed to assess tacrolimus therapy
      in patients who fail to respond to standard immunosuppressive therapy.

PMID- 11443589
TI  - Statins as immunosuppressive agents.
AB  - BACKGROUND: Coronary artery disease in the transplanted heart, also known as
      cardiac allograft vasculopathy, is one of the major causes of mortality late
      after heart transplantation. This accelerated form of atherosclerosis also
      affects the donor organs of other transplant recipients including that of liver,
      kidney and lung. There are multiple immune and non-immune risk factors associated
      with this disease process, one of which is hyperlipidemia. Use of lipid lowering
      agents, specifically HMG-CoA reductase inhibitors (statins) was initially
      reported to have outcomes benefit and possibly immunosuppressive effects in a
      single center study of heart transplant recipients. Other subsequent studies have
      supported this beneficial effect. METHOD AND RESULTS: In a recent paper by Kwak
      and colleagues, the specific mechanism for this immunosuppressive effect has been
      elucidated through the use of experiments monitoring cell surface expression
      assayed by fluorescence-activated cell sorting and by immunofluorescence as well
      as mRNA levels of major histocompatibility complex class II (MHC-II). They report
      that statins repress induction of MHC-II by interferon-gamma and that this in
      turn represses activation of T-lymphocytes and other cell types including primary
      human smooth muscle cells and fibroblasts, as well as in established cell lines
      such as ThP1, melanomas, and HeLa cells. CONCLUSION: In addition to previous
      clinical and laboratory publications this work by Kwak and colleagues has
      provided a firm scientific rationale to support the use of statins as adjunct
      immunosuppressive agents in organ transplantation.

PMID- 11443590
TI  - Hepatic xenotransplantation will benefit from strategies aimed to reduce
      complement activation.

PMID- 11443591
TI  - Synovitis subsequent to total-hip arthroplasty with and without hydroxyapatite
      coatings: a study in dogs.
AB  - OBJECTIVE: To establish whether hydroxyapatite (HA) coatings applied to metal
      total-hip-replacement components increased synovitis in the coxofemoral joint of
      dogs. Study Design-An in vivo research trial and histologic study. ANIMALS:
      Twenty-three large, mixed-breed dogs. METHODS: Arthroplasty components were
      implanted with HA on neither stem nor cup, or with HA applied to either the
      femoral component or with both stem and cup having HA applied in 23 dogs.
      Synovial inflammation was scored 3, 6, and 12 months after surgery. Synovial
      membrane thickness; polyethylene particulate load; fibrin exudate; membrane
      edema; mitotic index; giant-cell, mononuclear histiocyte, lymphocyte, and
      polymorph number; and collagen degeneration were scored and statistical analyses
      performed. RESULTS: Operated-side synovial thickness was greatly increased
      relative to control. Fibrin deposition, intramembranous edema, and collagen
      degeneration were similar within each time interval among the various component
      groups. The majority of inflammatory scores among the groups were unchanged. In
      this 12-month study, the presence of HA coatings appear not to have a marked
      impact on the development of synovial inflammation. CONCLUSIONS: HA-coated
      components do appear to contribute somewhat to the inflammatory load within the
      periprosthetic environment, but this effect is not marked. CLINICAL RELEVANCE:
      The major advantage of HA addition to arthroplasty components is enhanced
      osteoconductivity around metallic surfaces. The slight increase in particulate
      load seen in the presence of HA coatings may contribute to the development of
      aseptic loosening of arthroplasty components, but is unlikely to be the major
      causative factor.

PMID- 11443592
TI  - Use of an endoscopic suturing device for laparoscopic resection of the apex of
      the bladder and umbilical structures in normal neonatal calves.
AB  - OBJECTIVE: To develop a laparoscopic technique using an endoscopic suturing
      device for the resection of the apex of the bladder and the umbilical structures
      in large-animal neonates. Study Design-Experimental study. Animals or Sample
      Population-Seven healthy male Holstein calves. METHODS: A laparoscopic technique
      for resection of the apex of the bladder was developed on 2 calf cadavers, then
      evaluated on 5 anesthetized calves. The calves were positioned in dorsal
      recumbency, and 4 ventral abdominal portals were used. The umbilical vessels were
      double-ligated using an endoscopic suturing device and subsequently transected.
      The apex of the bladder was transected between a row of laparoscopic clips
      applied near the apex and atraumatic laparoscopic forceps applied distally; then,
      the edges were apposed using an endoscopic suturing device. The dissected
      umbilical remnants were removed from the abdomen through a small incision
      centered at the umbilicus. One month later, the calves were euthanatized and a
      second-look laparoscopy performed; then, bladders were collected for gross and
      histologic examination. RESULTS: No major complications occurred during or after
      surgery. The endoscopic suturing device permitted both effective ligation of the
      umbilical vessels and closure of the bladder. During second-look laparoscopy,
      healing of the peritoneal surface of the bladder and umbilical vessels was
      assessed to be excellent in 4 calves. A focal adhesion of omentum to the bladder
      suture line was observed in 1 calf. Focal adhesions of the omentum to the
      umbilical incision site occurred in 2 calves. The bladder mucosa was completely
      healed at the surgical sites. CONCLUSION AND CLINICAL RELEVANCE: Resection of the
      apex of the bladder and umbilical vessels in calves can be accomplished
      laparoscopically using an endoscopic suturing device.

PMID- 11443593
TI  - Penile amputation and sheath ablation in the horse.
AB  - OBJECTIVE: To report a surgical technique for penile amputation and sheath
      ablation in horses. Study Design-Retrospective study. Animals or Sample
      Population-Twenty-five adult geldings of various breeds with conditions requiring
      penile amputation and sheath ablation. METHODS: The medical records of horses
      that had penile amputation and sheath ablation were reviewed. Briefly, the
      technique involved en bloc resection of the skin and subcutaneous tissues of the
      inner and outer lamina of the prepuce and penile shaft. Resection of the penile
      shaft, proximal to diseased segments, and spatulation of the urethral mucosa was
      followed by fixation of the penis to the ventral abdomen and closure of the
      peripreputial skin over the ventral aspect of the penis and creation of a new
      mucocutaneous junction at the urethral orifice. RESULTS: Mild to moderate
      postoperative hemorrhage occurred in all horses. Partial dehiscence of the
      mucocutaneous junction occurred in 8 horses; all healed by second intention.
      Postoperative pain lasting 24 to 48 hours occurred in 7 horses; 1 required
      epidural analgesia for pain relief. Long-term follow-up was available for 8
      horses; none had any long-term complications. CLINICAL RELEVANCE: Partial
      amputation of the penis with pexy to the ventral abdomen and revision of the
      peripreputial skin can be used as an alternative to en bloc resection and penile
      retroversion for lesions involving the free part of the penis and the prepuce. It
      requires smaller incisions and results in less alteration to the normal
      appearance of the external genitalia than retroversion techniques, while still
      allowing the surgeon to remove extensive portions of the penis and extirpate the
      regional lymph nodes.

PMID- 11443594
TI  - A biomechanical comparison of headless tapered variable pitch and AO cortical
      bone screws for fixation of a simulated lateral condylar fracture in equine third
      metacarpal bones.
AB  - OBJECTIVE: To compare drilling, tapping, and screw-insertion torque, force, and
      time for the 4.5-mm AO and 6.5-mm Acutrak Plus (AP) bone screws, and to compare
      the mechanical shear strength and stiffness of a simulated complete lateral
      condylar fracture of the equine third metacarpal bone (MC3) stabilized with
      either an AO or AP screw. STUDY DESIGN: In vitro biomechanical assessment of
      screw-insertion variables, and shear failure tests of a bone-screw-stabilized
      simulated lateral condylar fracture. SAMPLE POPULATION: Eight pairs of cadaveric
      equine MC3s METHODS: Metacarpi were placed in a fixture and centered on a biaxial
      load cell in a materials-testing system to measure torque, compressive force, and
      time for drilling, tapping, and screw insertion. Standardized simulated lateral
      condylar fractures were stabilized by either an AO or AP screw and tested in
      shear until failure. A paired t test was used to assess differences between
      screws, with significance set at P < .05. RESULTS: Insertion and mechanical shear
      testing variables were comparable for AO and AP insertion equipment and screws.
      CONCLUSION: The 6.5-mm tapered AP screw can be inserted in equine third
      metacarpal condyles and is mechanically comparable with the 4.5-mm AO screw for
      fixation of a simulated lateral condylar fracture. CLINICAL RELEVANCE:
      Considering the comparable mechanical behavior, the potential for less-persistent
      soft-tissue irritation with the headless design, and the ability to achieve
      interfragmentary compression by inserting the screw in one hole drilled
      perpendicular to the fracture plane, the 6.5-mm tapered AP screw may be an
      attractive alternative for repair of incomplete lateral condylar fractures in
      horses.

PMID- 11443595
TI  - A comparative mechanical study of 3 external fixator clamps.
AB  - OBJECTIVE: To compare external fixator clamps from Kirschner-Ehmer (K-E),
      Synthes, and Meynard with respect to 6 mechanical parameters. Study Design-A
      bench test of mechanical properties. METHODS: Specially designed fixtures were
      used to mechanically test 6 clamps of each type at 2.5, 5.0, and 7.5 Newton
      Meters of clamp bolt-tightening torque. RESULTS: Components slipped axially and
      torsionally in the K-E clamp at higher forces for all parameters except for clamp
      bolt axis pivot. No bolt axis pivot occurred with the Synthes clamp. Instead, the
      clamp plastically deformed at the fixator-pin interface. This failure occurred at
      a higher applied torque than the pivot torque for other clamps. The Meynard clamp
      withstood significantly greater force than the K-E clamp when torsion was applied
      to the clamp bolt axis in the clockwise direction. Pivot forces for the K-E clamp
      were significantly higher than the Meynard clamp in the counterclockwise
      direction. CONCLUSIONS: Overall, the K-E clamp was able to resist higher axial
      and torsional forces before slipping than the Meynard clamp or the Synthes clamp.
      The Synthes clamp was best able to resist torsion around the clamp bolt axis.
      Torsional resistance at the clamp-fixator pin and clamp-connecting bar interface
      was the weakest parameter of clamp mechanics. CLINICAL RELEVANCE: The ability to
      resist motion within a clamp is related to fracture-reduction stability.
      Knowledge of the mechanical properties of fixator clamps will improve a
      clinician's ability to apply rigid fixation.

PMID- 11443596
TI  - Analgesic effect of the transdermal fentanyl patch during and after feline
      ovariohysterectomy.
AB  - OBJECTIVE: To evaluate the efficacy of the transdermal fentanyl patch in
      relieving perioperative pain and stress associated with ovariohysterectomy in
      cats. STUDY DESIGN: Prospective laboratory trial. ANIMALS: Twenty-four female,
      purpose-bred cats. METHODS: Each cat was randomly assigned to groups 1-3. Group 1
      received a 25-microg/h transdermal fentanyl patch only. Group 2 received the
      patch and anesthesia. Group 3 received anesthesia only. Patches were left in
      place for 72 hours. Rectal temperature, heart rate, respiratory rate, indirect
      blood pressure, blood glucose, serum cortisol concentration, plasma fentanyl
      concentration, pain score, and excitement/sedation score were monitored at
      prescribed intervals over an 81-hour period. Cats from groups 1-3 were reassigned
      to groups 4 and 5. Group 4 received the patch, anesthesia, and an
      ovariohysterectomy. Group 5 received anesthesia and an ovariohysterectomy only.
      The study period and monitored parameters were the same as for groups 1-3.
      RESULTS: Serum cortisol concentrations were significantly lower in group 4 than
      group 5 during the surgical and early postsurgical time periods. A similar effect
      was noted in blood glucose concentrations during the surgical period. Rectal
      temperature was significantly higher in group 2 when comparing all anesthetized
      groups during the early postsurgical period. Pain scores were significantly
      higher in groups 4 and 5 than in groups 2 and 3 during the early postsurgical
      period. There was no significant difference in pain scores between groups 4 and 5
      during this period, however. CONCLUSIONS: The transdermal fentanyl patch affects
      biochemical markers of perioperative pain and stress associated with
      ovariohysterectomy in cats, attenuating rises in serum cortisol and blood glucose
      concentrations during the surgical and early postsurgical periods. CLINICAL
      RELEVANCE: The transdermal fentanyl patch is effective in alleviating
      perioperative pain and stress associated with ovariohysterectomy in cats as
      evidenced by attenuated rises in cortisol and blood glucose concentrations in
      cats that were operated on and treated with the patch.

PMID- 11443597
TI  - A comparison of the effects of unilateral thyroarytenoid lateralization versus
      cricoarytenoid laryngoplasty on the area of the rima glottidis and clinical
      outcome in dogs with laryngeal paralysis.
AB  - OBJECTIVE: To compare the clinical effects of unilateral thyroarytenoid
      lateralization versus unilateral cricoarytenoid laryngoplasty for the treatment
      of canine laryngeal paralysis. Study Design-A prospective, clinical trial.
      ANIMALS: Twenty client-owned dogs admitted to Glasgow University Veterinary
      Hospital (GUVH) between 1997 and 1999 with a diagnosis of laryngeal paralysis.
      METHODS: A thorough evaluation of each dog was undertaken that included history,
      physical and neurologic examinations, complete blood count, serum biochemistry
      profile, serum thyroxine (T4) level, and thyroid-stimulating hormone (TSH) assay.
      The exercise tolerance of each dog was investigated by assessing respiratory rate
      and arterial blood gas analysis at rest and after 5 minutes of mild exercise.
      Animals were included in the study on the basis of a definitive diagnosis of
      laryngeal paralysis made by endoscopic observation of the larynx in the lightly
      anesthetized patient. The animals were randomly assigned to 1 of 2 treatment
      groups: unilateral thyroarytenoid lateralization or unilateral cricoarytenoid
      laryngoplasty, with all procedures being performed by the same surgeon. Video
      images of the rima glottidis were recorded pre- and postoperatively using video
      endoscopy. Video images were digitized and the area of the rima glottidis
      measured using image-analysis software. An increase in the area of the rima
      glottidis was expressed as a percentage of the preoperative area. All animals
      were reassessed 6 weeks' postoperatively, and exercise tolerance tests were
      repeated. RESULTS: The mean increase in the area of the rima glottidis
      postoperatively when compared with the preoperative area was 140% for those
      animals undergoing unilateral thyroarytenoid lateralization (range, 120%-158%)
      and 207% for those animals undergoing unilateral cricoarytenoid laryngoplasty
      (range, 183%-228%). This difference was statistically significant (P < .0001). At
      the 6-week postoperative examination, there was no significant difference in
      improvement between the 2 groups when compared on either a clinical basis or
      exercise tolerance tests. The mean surgical time in the 2 groups was 25 minutes
      for thyroarytenoid lateralization and 43 minutes for cricoarytenoid
      laryngoplasty. This was a statistically significant difference (P = .002).
      CONCLUSION: Although increase in area of the rima glottidis was significantly
      greater after unilateral cricoarytenoid laryngoplasty compared with unilateral
      thyroarytenoid lateralization, no difference in clinical outcome could be
      detected. However, the cricoarytenoid laryngoplasty procedure required
      significantly more surgical time. CLINICAL RELEVANCE: Both unilateral
      cricoarytenoid laryngoplasty and unilateral thyroarytenoid lateralization are
      successful methods for the treatment of laryngeal paralysis; however,
      thyroarytenoid lateralization requires less surgical time to perform.

PMID- 11443598
TI  - Comparison of two methods for presurgical disinfection of the equine hoof.
AB  - OBJECTIVES: To determine for equine hooves the normal resident aerobic bacterial
      population and the efficacy of 2 methods of disinfection. Study Design
      Measurement of total bacterial, gram-positive bacterial, and gram-negative
      bacterial surface populations from the frog, sole, and hoof wall after each step
      of 2 different preoperative surgical disinfection techniques. ANIMALS: Six adult
      horses. METHODS: Hoof wall, sole, and frog samples were collected for
      quantitative bacteriology before, during, and after 2 multistep antiseptic
      preparation techniques: Method A-6-minute scrub with povidone-iodine soap,
      followed by 24-hour submersion in povidone-iodine solution-soaked cotton; and
      Method B-initial removal of superficial layer of hoof capsule before completing
      Method A disinfection procedures. RESULTS: Removal of the superficial hoof layer,
      application of the povidone iodine scrub, and completion of the povidone-iodine
      soak all significantly (P < .0008) decreased total bacterial numbers. Method B
      had significantly lower bacterial counts than method A at each consecutive step.
      Final total bacterial counts remained greater than 10(5) bacteria per gram of
      tissue regardless of preparation method. CONCLUSIONS: The hoof surface hosts a
      broad spectrum of aerobic gram-positive and -negative bacteria, many of which are
      potential pathogens. Bacterial numbers can be significantly reduced by removal of
      the superficial hoof surface, by application of a povidone-iodine scrub, and by
      use of a 24-hour povidone-iodine soak. However, bacterial populations >10(5) g
      per tissue persist after these disinfection procedures. CLINICAL RELEVANCE:
      Regardless of the preparation methods used in this study, bacterial populations
      capable of inducing wound infection remain on the hoof capsule.

PMID- 11443599
TI  - Effects of epidural anesthesia on microcirculatory blood flow in free medial
      saphenous fasciocutaneous flaps in dogs.
AB  - OBJECTIVE: To assess the effects of epidural anesthesia using lidocaine on
      microcirculatory blood flow, volume, and velocity in free fasciocutaneous flaps
      in dogs. Study Design-In vivo experimental investigation. Animal Population-Ten
      adult dogs weighing 20 to 25 kg. METHODS: A medial saphenous fasciocutaneous free
      flap was removed and an orthotopic transfer was performed by anastomosing the
      primary flap vessels back to the medial saphenous vessels. Blood flow
      (mL(LD)/min/100 g), volume (%volume or tissue hematocrit) and velocity (mm/s) in
      the flap were recorded throughout the procedure. After epidural anesthesia, blood
      flow, volume, and velocity values were again recorded. RESULTS: Microcirculatory
      blood flow, volume, and velocity, as measured by a laser-Doppler flowmeter,
      failed to reveal any significant changes over time. Immediately after epidural
      anesthesia, mean arterial pressure was significantly reduced and remained
      depressed throughout the experimental procedure. CONCLUSIONS: Epidural anesthesia
      combined with general anesthesia does not improve microcirculatory flow in free
      flaps in the pelvic limbs of dogs. No significant change in blood flow to the
      medial saphenous fasciocutaneous free flap occurred after division and
      anastomosis of the vascular pedicle. CLINICAL RELEVANCE: We recommend that
      epidural anesthesia with 2% lidocaine be used with caution in dogs undergoing
      microvascular free-flap transfer.

PMID- 11443601
TI  - Axial characteristics of circular external skeletal fixator single ring
      constructs.
AB  - OBJECTIVE: Evaluate the effects of varying ring diameter, wire tension, and wire
      divergence angle on the axial stiffness characteristics of circular external
      skeletal fixator single-ring constructs. Study Design-Biomechanical evaluation
      using circular fixator components and a Delrin cylinder bone model. METHODS:
      Single ring constructs using two 1.6 mm diameter Kirschner wires to secure a 19
      mm Delrin cylinder centered within the ring were examined. Component variables
      evaluated were ring diameter (50 mm, 66 mm, 84 mm, and 118 mm), wire-divergence
      angle (30 degrees, 60 degrees, and 90 degrees ), and wire tension (0 kg, 30 kg,
      60 kg, and 90 kg). A total of 48 constructs were examined. Rings were rigidly
      mounted on a universal testing system and the cylinder loaded in axial
      compression (7.4 N/s) to 220 N. Load/displacement curves were analyzed to
      determine the following: the displacement (mm) that occurred before the slope of
      each load/displacement curve became linear, the stiffness (N/mm) of the linear
      portion of each load/deformation curve, and the total displacement (mm) produced
      at maximal load. Least-squares linear regression was used to model response
      variables as linear functions of ring diameter, wire divergence angle, and wire
      tension. Three-way interactions and 2-way interactions among independent
      component variables were evaluated first in the modeling process and included in
      a best model if response variables were found to have statistically significant
      regression coefficients. The regression coefficients and corresponding standard
      errors and covariances were used to estimate the maximal effect and standard
      error attributable to wire divergency angle (change from 30 degrees to 90 degrees
      ) and wire tension (change from 0 to 90 kg) for each ring diameter. RESULTS: All
      load/deformation curves had an initial exponential increase in stiffness, with
      the slope becoming linear at higher loads. The exponential phase was more
      pronounced in larger-diameter ring constructs and was mitigated by tensioning the
      wires. Ring diameter had the greatest influence on displacement that occurred
      before the curve became linear (semipartial r(2) [sp-r2] = .89), stiffness (sp-r2
      = .94), and total displacement (sp-r2 = .93). Wire tension exerted a smaller
      influence on displacement that occurred before the curve became linear (sp-r2
      =.06), stiffness (sp-r2 = .03), and total displacement (sp-r2 = .05). Wire
      divergence angle had a nominal effect on displacement that occurred before the
      curve became linear (sp-r2 = .0001), on stiffness (sp-r2 = .004), and on total
      displacement (sp-r2 =.003). CONCLUSIONS: Ring diameter had a profound effect on
      the axial stiffness characteristic of single ring constructs. Tensioning of the
      fixation wires can improve the axial stiffness characteristics of these
      constructs, particularly in larger diameter ring constructs, by mitigating the
      initial exponential phase of the load/deformation curve. Wire divergence angle
      had only a nominal differential effect on axial stability. CLINICAL RELEVANCE:
      Understanding how individual component variables and their interactions influence
      bone segment stability should help surgeons to optimize interfragmentary strain.
      Tensioning fixation wires is probably unnecessary in 50 mm diameter ring
      constructs, but assumes greater importance as ring diameter increases.

PMID- 11443600
TI  - Combined omental pedicle grafts and thoracodorsal axial pattern flaps for the
      reconstruction of chronic, nonhealing axillary wounds in cats.
AB  - OBJECTIVE: To assess the results of an omental pedicle graft in combination with
      a thoracodorsal axial pattern flap for the reconstruction of chronic nonhealing
      axillary wounds in 10 cats caused by forelimb entrapment within a collar. STUDY
      DESIGN: A prospective, clinical trial. ANIMALS USED: Ten client-owned domestic
      shorthair cats. METHODS: Routine biochemical and hematologic evaluation was
      performed on each cat, and all were tested for feline immunodeficiency virus
      (FIV) and feline leukemia virus (FeLV). Microbial culture was performed on
      samples from the wounds. After surgical debridement, omentalization using a
      vascular pedicle of greater omentum, and closure of the chronic axillary wounds,
      using a thoracodorsal axial pattern flap, was performed. All excised tissue was
      examined histologically. RESULTS: The sex distribution was 7 males and 3 females,
      with a mean age of 3.5 years. The cats had undergone a median number of 3
      previous repair attempts over a 1.5- to 25-month period before referral (mean,
      10.2 months). No hematologic or biochemical abnormalities were noted apart from
      moderately elevated creatine kinase and aspartate transaminase concentrations in
      some cats. All cats were negative for FIV and FeLV. Histologic examination of
      resected tissue revealed hair (foreign body) in 2 cats and an unidentified
      foreign-body reaction in 3 other cats. Complete healing occurred in all cats
      (mean follow-up period of 21.7 months), with 2 cats requiring further surgery: 1
      for flap dehiscence at 4 days after surgery, and 1 for donor-site dehiscence at 4
      days after surgery. One other cat developed a large seroma in the axilla that
      resolved by 10 days following surgery. CONCLUSION: The use of an omental pedicle
      graft in combination with a thoracodorsal axial pattern flap is the first
      consistently successful 1-step technique for the management of chronic nonhealing
      axillary wounds in cats.

PMID- 11443602
TI  - Consanguinity and family history of cancer in children with leukemia and
      lymphomas.
AB  - BACKGROUND: In native population of the United Arab Emirates (UAE), the rate of
      consanguineous marriages is 50.5%. This study was designed to determine whether
      the rates of consanguinity and family history of cancer among the families of
      children with lymphoid malignancy are different from those in the general
      population. METHODS: The study comprised 117 patients from the whole of the
      country with acute lymphocytic leukemia (ALL) and Hodgkin lymphoma (HL) and non
      Hodgkin lymphoma (NHL), ranging in age from 2 to 14 years. The consanguinity rate
      in the study group was compared with the rate in the general population. To study
      family history of cancer, the authors matched patients with 117 controls. In a
      telephone interview, each mother was asked to provide data regarding the biologic
      relationship between her and her husband as well as that between both sets of
      grandparents; each was also asked whether any family relative had a cancer and,
      if so, of what type. RESULTS: Among the 69 ALL cases, 80% of families were
      consanguineous and 20% were nonconsanguineous. Among the 26 NHL and 22 HL cases,
      each group included 3 consanguineous families, 12% and 14%, respectively. The
      consanguinity rates for ALL, NHL, and HL were all significantly different from
      the 50.5% consanguinity rate in the UAE population (all three P values < 0.0001).
      The family history of cancer was more often positive in ALL patients than in
      controls (odds ratio, 2.14; confidence interval, 1.01--4.53). Overall and for
      each lymphoid malignancy, there was no difference in family history of cancer
      between consanguineous and nonconsanguineous groups of cases. CONCLUSIONS: The
      consanguinity rate in the families of patients with ALL is significantly higher
      and in those with NHL and HL significantly lower than that in the UAE population.
      The family history of cancer is more often positive among ALL cases than controls
      -consanguinity having no effect.

PMID- 11443603
TI  - High-dose liposomal daunorubicin and high-dose cytarabine combination in patients
      with refractory or relapsed acute myelogenous leukemia.
AB  - BACKGROUND: Liposomal encapsulation of daunorubicin (DaunoXome, DNX; Nexstar
      Pharmaceutical, Boulder, CO) changes the pharmacology profile to increase
      delivery to tumor sites and decrease toxicity. The authors investigated the
      effect of daunorubicin in combination with ara-C in patients with refractory or
      recurring acute myelogenous leukemia (AML). PATIENTS AND METHODS Sixty-two
      patients with refractory or recurring AML received escalating doses of
      daunorubicin of 75, 100, 125, or 135 mg/m(2) daily for 3 days together with ara-C
      1 g/m(2) intravenous continuous infusion daily for 4 days. RESULTS: Eighteen
      patients (29%) achieved a complete remission (CR) and 7 (11%) a hematologic
      improvement (i.e., met all criteria for CR except for platelet count < 100 x
      10(9)/L) for an overall response rate of 40%. The dose-limiting toxicity was
      mucositis in 4 in 9 (44%) patients treated at the 150 mg/m(2) dose level, but
      minimal at 125 mg/m(2) (2 of 32, 6%) or 135 mg/m(2) (1 of 13, 8%). Cardiotoxicity
      Grade 2 was observed in 4 patients (6%) and Grade 3 or higher in 4 patients (6%).
      The median CR duration was 63 weeks, and overall survival rate was 25 weeks, with
      28% patients alive after 1 year. CONCLUSIONS: The combination of DNX (or
      liposomal daunorubicin) and ara-C has significant antileukemia activity with
      acceptable toxicity. Further studies are warranted to investigate the role of
      high-dose anthracyclines in frontline AML therapy.

PMID- 11443604
TI  - Excellent therapeutic efficacy and minimal late neurotoxicity in children treated
      with 18 grays of cranial radiation therapy for high-risk acute lymphoblastic
      leukemia: a 7-year follow-up study of the Dana-Farber Cancer Institute Consortium
      Protocol 87-01.
AB  - BACKGROUND: In the current study, the authors evaluated late neuropsychologic
      effects 7 years after diagnosis and the long-term survival in a cohort of
      patients treated for high-risk childhood acute lymphoblastic leukemia (ALL) with
      cranial radiation therapy. Efficacy and toxicity were evaluated in relation to
      patient age at diagnosis (age < or > or = 36 months). METHODS: Two hundred and
      one patients treated for high-risk ALL on the Dana-Farber Cancer Institute
      Consortium Protocol 87-01 were included, 147 of whom were in continuous complete
      disease remission and were eligible for cognitive testing. Sixty-one patients
      consented to undergo testing. All patients received 18 grays (Gy) of cranial
      radiation as a component of central nervous system treatment. RESULTS: For all
      201 patients, the 5-year overall survival (% +/- the standard error) was 82% +/-
      2 and the 5-year event-free survival (% +/- the standard error) was 75% +/- 3.
      Only two patients developed a central nervous system recurrence. Intelligence
      quotient (IQ) and memory were at the expected mean for age, but performance on a
      complex figure drawing task was found to be reduced. Children who were age < 36
      months at the time of diagnosis were found to have an IQ in the average range,
      but showed verbal deficits. CONCLUSIONS: The results of the current study
      demonstrate excellent efficacy of therapy and relatively limited late
      neurotoxicity on a childhood ALL therapy protocol in which all evaluated patients
      had received 18 Gy of cranial radiation. Efficacious therapy that includes
      cranial radiation does not appear to necessarily incur a heightened risk for
      significant cognitive impairment.

PMID- 11443605
TI  - A comparison of four treatment strategies for ductal carcinoma in situ using
      decision analysis.
AB  - BACKGROUND: The goals of the current study were to compare four treatment
      approaches in the management of ductal carcinoma in situ (DCIS), to determine the
      conditions where mastectomy may be preferred to breast-conserving therapy (BCT),
      and to determine conditions where the addition of tamoxifen produces better
      results than BCT alone. METHODS: A decision analysis model was used to compare
      four treatment approaches after local excision for DCIS: mastectomy, irradiation,
      irradiation plus adjuvant tamoxifen, or observation. The model weighed the
      potential benefits of each treatment approach (reduction of ipsilateral and/or
      contralateral breast carcinoma) against the potential risks of treatment-related
      toxicities. In addition, the model adjusted for the potential detrimental impact
      of local recurrence or treatment-related toxicity on health-related quality of
      life (HRQOL). Base-case estimates were obtained from published randomized trial
      data. One-way and two-way sensitivity analyses were performed. RESULTS: According
      to the model, the optimal treatment for DCIS was strongly dependent on the
      individual's risk of local recurrence and the patient's attitudes toward
      mastectomy. Mastectomy was preferred in patients whose estimated 10-year risk of
      local recurrence was > 15%, provided that mastectomy resulted in a very low
      reduction in quality of life (i.e., utility estimate > 0.97). Conditions where
      the addition of tamoxifen was preferred to breast-conserving therapy alone
      included the following: estimated 10-year risk of local recurrence > 38%,
      estimated 10-year risk of developing a contralateral breast carcinoma > 6%, or a
      significant decrement in HRQOL associated with the development of an invasive
      local recurrence or salvage mastectomy (utility estimates < 0.85). CONCLUSION:
      Based on this quality-adjusted model, BCT appeared to be the preferred treatment
      for DCIS. The most important determinants of optimal management for DCIS included
      the risk of local recurrence and the utility of mastectomy. Formal evaluation of
      utilities in the context of DCIS and more accurate determination of the risk of
      recurrence are required.

PMID- 11443606
TI  - No elevation in long-term breast carcinoma risk for women with fibroadenomas that
      contain atypical hyperplasia.
AB  - BACKGROUND: The authors previously showed that women with a fibroadenoma have a
      relative risk of invasive breast carcinoma of approximately 2.0 compared with
      women of similar age from the general population. This relative risk approaches
      1.0 when family history and proliferative changes in the adjacent parenchyma are
      removed and rises to > 3.0 if the fibroadenoma has complex histology. The risk
      for developing breast carcinoma in women with atypical lobular hyperplasia (ALH)
      and atypical ductal hyperplasia (ADH) or their minimal variants within a
      fibroadenoma is unknown. METHODS: The authors conducted a long-term,
      retrospective cohort study of 1834 women with adequate follow-up who presented
      with fibroadenoma at three local hospitals between 1950 and 1968. Histology was
      reviewed using established criteria, and the patients were categorized with ALH,
      ADH, minimal atypia, or no atypia. RESULTS: The overall prevalence of ALH or ADH
      within fibroadenomas was 0.81%. Minimal or true atypia within a fibroadenoma
      appeared to be correlated with proliferative disease in the adjacent parenchyma
      but could not predict for the presence there of well-established atypia. Only 7%
      of women with well-developed atypia developed invasive carcinoma on follow-up.
      Three women with minimal atypia developed invasive carcinoma. CONCLUSIONS: In
      this study of a large cohort of women with fibroadenoma, the authors found that
      atypia within a fibroadenoma cannot predict for the presence of atypia within
      adjacent breast parenchyma. They also found that atypia confined to a
      fibroadenoma does not incur a clinically meaningful risk of future breast
      carcinoma development greater than that of fibroadenoma alone.

PMID- 11443607
TI  - Frequency distributions of breast cancer characteristics classified by estrogen
      receptor and progesterone receptor status for eight racial/ethnic groups.
AB  - BACKGROUND: The National Cancer Institute's Surveillance, Epidemiology, and End
      Results (SEER) cancer registries have been collecting data regarding estrogen
      receptor (ER) and progesterone receptor (PR) status in breast cancer since 1990.
      The current study reports on some of these data for eight racial/ethnic groups.
      METHODS: Stratified by ER and PR status, the frequency distributions of 112,588
      breast cancer cases diagnosed between 1992--1997 in 11 SEER cancer registries
      were examined by age at diagnosis, stage at diagnosis, histologic grade, and
      tumor type for white, black, Hispanic, Japanese, Chinese, Filipino, Native
      Hawaiian, and American Indian and Alaska Native (AI/AN) females. RESULTS: For
      each racial/ethnic group, the percentage of ER positive (+)/PR+ was > ER-PR- >
      ER+PR- > ER-PR+ tumors. For the two major ER/PR groups, the ER+PR+ tumors were
      different from the ER-PR- tumors in several ways. For white females, there were
      differences in the age distributions, stage at diagnosis, and histologic grade.
      For black females, the differences involved the age distributions and tumor
      grades. For Hispanic and Japanese females, there were differences with regard to
      the age distributions and tumor grades. For Filipino, Chinese, and AI/AN females,
      the tumor stages and grades differed. For Native Hawaiians, the histologic tumor
      grades were different. CONCLUSIONS: For each racial/ethnic group, the ER/PR
      status appeared to divide breast cancer patients into two or more subgroups with
      unique tumor characteristics. In general, ER status appeared to have the greatest
      impact on delineating these subgroups, whereas in some cases, PR status was able
      to modify the subgroups further. It is hoped that reporting these tumor
      characteristics by ER/PR status for each racial/ethnic group will spur more
      investigation into the significance of ER/PR status in each racial/ethnic group.

PMID- 11443608
TI  - The fate and prognostic value of occult metastatic cells in the bone marrow of
      patients with breast carcinoma between primary treatment and recurrence.
AB  - BACKGROUND: The current study examines the fate of occult metastatic cells
      detected in bone marrow (BM) at primary diagnosis and evaluates whether
      persistently positive findings support the prognostic influence of these cells in
      patients with Stage I--III (International Union Against Cancer) breast carcinoma.
      METHODS: The authors analyzed BM aspirates, at the time of primary diagnosis and
      after a median interval of 19 months (range, 7--67 months), from 89 patients who
      were free of recurrence. The presence of cytokeratin (CK) positive cells was
      assessed with the monoclonal anti-CK antibody A45-B/B3. Patients were observed
      prospectively for a median of 41 (range, 12--78) months after the first
      aspiration. RESULTS: At the time of primary diagnosis, 24 of 89 patients (27%)
      presented with occult metastatic cells in the BM. Of the same 89 patients, 25
      (28%) had a positive BM finding at the time of the second BM analysis. Among
      those patients with an initially negative BM finding, 15 patients (17%) had
      occult metastatic cells at time of the second BM aspiration, whereas 10 patients
      (11%) had a persistently positive BM finding. Patients with a persistently
      negative BM status (n = 50) had a significantly better overall survival than
      patients with a positive BM status at the time of the second BM aspiration (n =
      25), both by univariate analysis (P = 0.045, log-rank) and multivariate analysis
      (P = 0.034, Cox regression). CONCLUSIONS: In many patients with primary breast
      carcinoma, minimal residual disease can be detected by follow-up examination of
      the BM. This finding is prognostically relevant and provides reason to include BM
      monitoring in future clinical trials.

PMID- 11443609
TI  - Prognostic significance of BRCA1 expression in Japanese sporadic breast
      carcinomas.
AB  - BACKGROUND: BRCA1 is a tumor suppressor gene that is responsible for hereditary
      breast and ovarian carcinoma syndrome. The primary objective of the current study
      was to investigate the influence of BRCA1 expression on the prognoses of sporadic
      breast carcinomas. METHODS: A cohort of 175 Japanese women with invasive breast
      carcinoma who had no family history in first-degree relatives was studied.
      Expression of BRCA1 was determined by an immunohistochemical procedure in which
      the MS110 monoclonal antibody was used. Kaplan--Meier and Cox proportional
      regression survival analyses were used to compare negative and positive BRCA1
      patients. RESULTS: One hundred fifteen (65.7%) of the 175 specimens showed
      positive BRCA1 staining (> 10% cells were immunoreactive). During a median follow
      up of 4.4 years, negative BRCA1 patients had worse disease free survival than
      positive BRCA1 patients (35 % vs. 7%, respectively; P < 0.0001). BRCA1 expression
      was significantly inversely correlated with histologic grade (P < 0.0001) but not
      with lymph node status or other conventional prognostic markers. In multivariate
      analysis using the Cox regression model, positive BRCA1 emerged as an independent
      prognostic indicator for disease free survival. CONCLUSIONS: The results of this
      study suggest that BRCA1 may be a valuable marker for identifying women with
      sporadic breast carcinoma at high risk of developing recurrence, and who may be
      candidates for trials investigating new therapies in combination with standard
      adjuvant therapy.

PMID- 11443610
TI  - Reduced C-terminal Src kinase activity is correlated inversely with pp60(c-src)
      activity in colorectal carcinoma.
AB  - BACKGROUND: Specific kinase activity of the proto-oncogene product pp60(c-src) is
      reported to be elevated in patients with carcinoma of the colon, and a novel
      cytoplasmic protein-tyrosine kinase, C-terminal Src kinase (Csk), has been found
      to inactivate the members of the Src family protein-tyrosine kinase. In this
      study, Csk activity and pp60(c-src) activity were examined in colorectal tumors
      as well as in colon carcinoma cell lines. METHODS: Colorectal carcinoma tissue
      and adjacent nonneoplastic tissue from 24 patients, from 8 colon carcinoma cell
      lines, and from 1 normal colon cell line were used. The levels of pp60(c-src) and
      Csk in colorectal tissue and cell lines were analyzed by Western and/or Northern
      blot analysis, and their kinase activity levels were measured by in-gel kinase
      assay. RESULTS: In the samples from 24 patients with colorectal carcinoma, pp60(c
      src) kinase activity and protein levels were increased by 7.8 +/- 0.55 and 2.6 +/
      0.13 times the control levels, respectively. Conversely, the Csk protein level
      and its kinase activity were reduced by 0.53 +/- 0.08 and 0.53 +/- 0.09 times the
      control levels, respectively. pp60(c-src) kinase activity was correlated
      inversely with Csk activity (correlation coefficient = -0.71; P < 0.0001). Of the
      cell lines, pp60(c-src) kinase activity and protein levels, respectively, were
      7.4 +/- 1.22 and 1.86 +/- 0.28 times greater than normal control levels. Csk
      protein level and kinase activity, respectively, were 0.54 +/- 0.13 and 0.52 +/-
      0.11 times less normal control levels and were correlated with mRNA amount.
      CONCLUSIONS: Csk mRNA, protein, and its kinase activity were reduced in
      colorectal carcinoma and were correlated with pp60(c-src) kinase activity level.
      The reduced activity of Csk may be involved in the transformation of a subset of
      colorectal carcinoma.

PMID- 11443611
TI  - Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by
      complete resection and intraperitoneal chemotherapy.
AB  - BACKGROUND: Peritoneal carcinomatosis (PC) is fatal, despite standard systemic
      chemotherapy. A new approach that combines maximal surgery with maximal regional
      chemotherapy has potential to cure selected patients who have colorectal PC. The
      authors have reported the oncologic results of this combined treatment. METHODS:
      The authors performed a retrospective study of 64 patients who had PC arising
      from colorectal adenocarcinomas, 19 (29.6%) of whom also had other metastases.
      These patients were treated by complete resection of all detectable tumors and by
      a 5-day course of early intraperitoneal chemotherapy (EPIC) with mitomycin C,
      then by 5-fluorouracil (n = 37), or by intraoperative intraperitoneal
      chemohyperthermia (IPCH) with mitomycin C, alone or combined with cisplatin (n =
      27), in 2 separate trials. In the trial of IPCH, aimed at selecting the most
      reliable procedure in terms of spatial diffusion and thermal homogeneity, the 27
      patients were treated with 7 different procedures. The extent of PC was assessed
      precisely by using a peritoneal index. The median follow-up period for the entire
      patient population was 51.7 months. RESULTS: The postoperative mortality and
      morbidity rates were 9.3% and 54.6%, respectively. Most severe complications
      occurred in patients who required extensive cytoreductive surgery. Global and
      disease-free survival rates were respectively 60.1% and 54.7% at 2 years and were
      27.4% and 18.4% at 5 years. Results were significantly better (P = 0.04) when
      patients were metastasis-free (apart from PC) and when the peritoneal index was
      lower than 16 (P = 0.005). IPCH seemed to be more effective than EPIC for
      treatment of PC. CONCLUSION: This treatment plan, which combined maximal surgery
      with maximal regional chemotherapy, cured approximately 25% of patients. This
      strategy was mainly applicable to patients with limited intraperitoneal cancer
      volume and no extraperitoneal involvement. IPCH proved to be more effective than
      EPIC but more difficult to use correctly. Future results should improve through
      routine use of the optimal hyperthermia procedure, with improvements in the
      composition of instillate, better patient selection, and the reduction in the
      rate of complications that occurs with physician experience.

PMID- 11443612
TI  - Management of inguinal lymph node metastases in patients with carcinoma of the
      anal canal: experience in a series of 270 patients treated in Lyon and review of
      the literature.
AB  - BACKGROUND: The authors performed a specific analysis of the clinical
      significance of inguinal lymph nodes metastases in patients with anal canal
      carcinoma (ACC). METHODS: A retrospective analysis was conducted of 270 patients
      who were treated in Lyon between 1980 and 1996 with radiotherapy with curative
      intent for ACC: No elective irradiation of clinically normal inguinal areas was
      performed. Patients with metastatic inguinal lymph nodes were treated with
      inguinal dissection and postoperative irradiation with a dose of 50 grays over 5
      weeks. Concomitant chemoradiation, usually with a regimen of fluorouracil and
      cisplatinum, was given to 159 patients. RESULTS: The median follow-up for the
      whole series was 72 months. Synchronous inguinal metastases were observed in 10%
      of patients (n = 27; the rate was 16% for patients with T3--T4 lesions), and the
      5-year overall survival rate was 54.4%. Metachronous inguinal metastases were
      seen in 19 patients (7.8%), and the 5-year overall survival rate of these
      patients was 41.4%. An original finding was that, when the primary tumor clearly
      was located on a single lateral side of the anal canal, the inguinal lymphatic
      metastases was always homolateral to it (36 of 36 synchronous plus metachronous
      tumors). CONCLUSIONS: The data from this series of patients and a review of the
      literature are in favor of a selective approach in the management of inguinal
      lymph node involvement for patients with ACC, depending on the disease stage and
      the location of the primary tumors.

PMID- 11443613
TI  - Patients with pseudomyxoma peritonei associated with disseminated peritoneal
      adenomucinosis have a significantly more favorable prognosis than patients with
      peritoneal mucinous carcinomatosis.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a poorly understood condition
      characterized by disseminated intraperitoneal mucinous tumors, often with
      mucinous ascites. The term PMP has been applied historically as a pathologic
      diagnostic term to both benign and malignant mucinous neoplasms that produce
      abundant extracellular mucin, resulting in a variable and poorly predictable
      prognosis. A recent study reported a pathologic classification that separated
      patients into prognostically distinct groups, but the follow-up was relatively
      short. METHODS: Long-term follow-up data were analyzed for a previously reported
      series of 109 patients with PMP to examine the prognostic utility of a pathologic
      classification system that divided patients into three groups: disseminated
      peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and
      peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA
      I/D). Patients whose tumors were classified 25 DPAM (n = 65 patients) had disease
      that was characterized by histologically bland to low-grade adenomatous mucinous
      epithelium associated with abundant extracellular mucin and fibrosis, often with
      an identifiable appendiceal mucinous adenoma that was the source of the
      peritoneal lesions. Patients whose tumors were classified 25 PMCA (n = 30
      patients) had disease that was characterized by peritoneal lesions that displayed
      the cytologic and architectural features of mucinous carcinoma associated with
      extracellular mucin, often with an identifiable invasive mucinous adenocarcinoma
      of the gastrointestinal tract. Patients whose tumors were classified 25 PMCA-I (n
      = 11 patients) had peritoneal lesions that combined the features of DPAM and PMCA
      derived from well differentiated mucinous adenocarcinomas associated with
      adenomas. Patients whose tumors were classified 25 PMCA-D (n = 3 patients) had
      markedly atypical appendiceal adenomas associated with peritoneal lesions similar
      to PMCA. RESULTS: Patients with DPAM had 5-year and 10-year survival rates of 75%
      and 68%, respectively (mean follow-up, 96 months; median follow-up, 104 months).
      Patients with PMCA and PMCA-I/D had a significantly worse prognosis, with 5-year
      and 10-year survival rates, respectively, of 50% and 21% for PMCA-I/D (mean
      follow-up, 58 months; median follow-up, 51 months) and 14% and 3% for PMCA (mean
      follow-up, 27 months; median follow-up, 16 months; P = 0.0001). CONCLUSIONS: The
      term PMP should be used only as a clinical descriptor for patients who have the
      syndrome of mucinous ascites accompanied by a characteristic distribution of
      peritoneal mucinous tumors with the pathologic features of DPAM. DPAM should be
      used as a pathologic diagnostic term for patients with the bland peritoneal
      mucinous tumors associated with ruptured appendiceal mucinous adenomas and PMP.
      These patients should not be diagnosed with carcinoma, because they have disease
      that is distinct pathologically and prognostically from PMCA.

PMID- 11443614
TI  - A genome-wide study of microsatellite instability in advanced gastric carcinoma.
AB  - BACKGROUND: Microsatellite instability (MSI) has been described in many human
      carcinomas, including gastric carcinomas (GCs). There are inconsistent findings
      regarding the association of MSI with various subsets of GC with specific
      clinicopathologic features. The objective of this study was to define MSI in
      advanced GC at a genome-wide level and to evaluate the clinical relevance of MSI
      in these patients. METHODS: Forty-one gastric adenocarcinomas with serosa
      invasion (T3) were analyzed at 59 loci that detected at least one site per arm of
      each autosome in human genome. The expression patterns of mismatch repair
      proteins hMLH1 and hMSH2 were examined by immunohistochemistry. Comparisons were
      made by categorizing tumors into three groups: tumors with MSI at multiple loci
      (at more than three loci), tumors with MSI at low level (at one to three loci),
      and microsatellite-stable (MSS) tumors. Clinical significance of MSI in advanced
      GC was evaluated. The relative rates of hypermutability of the 59 markers also
      were determined. RESULTS: A significant association was found between tumors with
      MSI at multiple loci and the expanding type of tumor growth by Ming's histologic
      classification (P = 0.001), whereas tumors with MSI at low level and MSS tumors
      are clinicopathologically indistinguishable. The 59 dinucleotide repeat markers
      displayed varying degrees of susceptibility toward genetic instability. The
      relative rates of hypermutability of these markers were consistent with a normal
      distribution pattern in which the frequency of unstable tumors detected at
      different chromosomal loci varied from 0% to 20%. CONCLUSIONS: The authors'
      results showed that advanced GC with MSI at multiple loci progress preferentially
      in an expanding mode, supporting the notion that high MSI tumors and low MSI/MSS
      tumors evolve through different genetic pathways. Thus, microsatellite testing
      may have clinical utility as a favorable prognostic marker.

PMID- 11443615
TI  - Determination of county-level prostate carcinoma incidence and detection rates
      with Medicare claims data.
AB  - BACKGROUND: To the authors' knowledge, national-level population-based data
      regarding prostate carcinoma incidence and detection currently are not available.
      The availability of such data could identify those regions with a
      disproportionately high cancer incidence as well as the population-level
      association between prostate carcinoma detection and incidence. METHODS:
      Inpatient, hospital outpatient, and physician/supplier Medicare claims from 1997
      were used to identify incident cases of prostate carcinoma in men age > or = 65
      years and to calculate state and county-level incidence rates. The 1991 and 1997
      claims data were used to determine small area rates of prostate-specific antigen
      (PSA) testing and prostate biopsy and to determine their correlation with
      incidence. RESULTS: The calculated incidence rates for 1997 were 890 per 100,000
      and 1196 per 100,000, respectively, in white males and African-American males and
      varied substantially between counties (i.e., 25--75th percentile, 676--1124 per
      100,000). Rates of PSA and prostate biopsy increased markedly from 1991 to 1997
      in both white men (1580 per 100,000 to 24,286 per 100,000) and African-American
      men (1277 per 100,000 to 15,190 per 100,000), and considerable variation in
      detection between counties was observed. Counties that had higher rates of
      prostate biopsy also had higher age-adjusted incidence rates, and county-level
      PSA testing was found to be associated with incidence in African-American
      patients, but not in white patients. CONCLUSIONS: Medicare claims may provide an
      alternative source of population-based data, particularly for areas in which
      registry data are not readily available or are of limited scope. In addition,
      claims provide otherwise unavailable national data concerning cancer detection.

PMID- 11443616
TI  - National survey of head and neck verrucous carcinoma: patterns of presentation,
      care, and outcome.
AB  - BACKGROUND: Verrucous carcinoma is distinguished by controversy regarding
      appropriate diagnosis and treatment. This study provides a contemporary survey of
      demographics, patterns of care, and outcome for this disease in the United
      States. METHODS: The National Cancer Data Base had 2350 cases of verrucous
      carcinoma of the head and neck diagnosed between 1985 and 1996. Statistical
      procedures included chi-square analyses, Student t tests, and relative survival.
      RESULTS: Tumors originated most frequently in the oral cavity (55.9%) and larynx
      (35.2%). Although most patients were male (60.0%), oral cavity tumors were more
      common among older females. The most prevalent treatment was surgery alone
      (69.7%), followed by surgery combined with irradiation (11.0%) and irradiation
      alone (10.3%). For oral cavity tumors, surgery alone was more common among early
      (85.8%) than advanced cases (56.9%); a larger proportion of advanced disease
      received radiation alone or surgery and irradiation combined. Most laryngeal
      tumors were treated with surgery (60.3% for early and 55.6% for advanced
      disease), but a higher proportion received radiation alone or surgery combined
      with radiation compared with oral cavity cases. Five-year relative survival was
      77.9%. For localized disease, survival after surgery was 88.9% compared with
      57.6% after irradiation. CONCLUSIONS: Demographic differences implicate different
      mechanisms of carcinogenesis for verrucous carcinoma arising in the oral cavity
      and the larynx. Although selection bias may account for the differences observed,
      patients receiving initial treatment with surgery had better survival than those
      treated with irradiation, especially for cases originating in the oral cavity.

PMID- 11443617
TI  - Routine brain imaging is unwarranted in asymptomatic patients with
      rhabdomyosarcoma arising outside of the head and neck region that is metastatic
      at diagnosis: a report from the Intergroup Rhabdomyosarcoma Study Group.
AB  - BACKGROUND: To the authors' knowledge, the incidence of brain metastases at the
      time of diagnosis in children with metastatic rhabdomyosarcoma (RMS) arising
      outside the head and neck region is unknown, and routine imaging to identify
      metastatic brain involvement is costly. METHODS: The authors retrospectively
      reviewed the results of computed tomography (CT) or magnetic resonance imaging
      (MRI) scans of the head, which was mandated by protocol, in patients with
      metastatic RMS arising outside the head and neck region who were enrolled on the
      fourth Intergroup Rhabdomyosarcoma Study (IRS-IV; 1991--1997). RESULTS: Of 100
      eligible patients with metastatic RMS arising outside the head and neck region,
      56 (56%) underwent head CT (n = 51) and/or MRI (n = 11) scans. Seven of these 56
      patients (12.5%) had abnormal scans. Three patients with physical findings
      suggesting head or neck pathology underwent imaging that confirmed the presence
      of metastases in bone (one patient), orbit (one patient), or lymph nodes (one
      patient). One patient who presented with seizures had imaging findings consistent
      with cerebral embolic infarctions. Of three asymptomatic patients, one had bone
      metastases that also were identified on skeletal survey and one had bone
      metastases in the base of the skull that were not identified on bone scan. The
      remaining asymptomatic patient had a retroperitoneal paraspinal tumor with spinal
      canal extension and subsequently developed leptomeningeal disease dissemination.
      CONCLUSIONS: Brain metastases are uncommon at the time of initial diagnosis of
      metastatic RMS arising outside the head and neck region, and the majority of
      abnormalities detected on head CT or MRI scans are evident clinically or on other
      imaging studies. Patients with clinical findings suggesting intracranial
      pathology and those with paraspinal tumors may benefit from brain imaging, but
      cost savings may be realized by foregoing imaging in patients without these
      features.

PMID- 11443618
TI  - Prognostic factors for survival in patients with compensated cirrhosis and small
      hepatocellular carcinoma after percutaneous ethanol injection therapy.
AB  - BACKGROUND: The objective of this study was to identify clinical, biochemical,
      ultrasound, and/or pathologic parameters capable of predicting survival in a
      cohort of patients with well compensated cirrhosis and small hepatocellular
      carcinoma (HCC) who were treated with percutaneous ethanol injection (PEI).
      METHODS: The study group included 111 patients with Child--Pugh Class A cirrhosis
      and with one (93 patients) or two (18 patients) HCC nodules measuring < 5 cm in
      greatest dimension. All patients underwent multisession PEI. The prognostic
      values of pretreatment and post-treatment variables were analyzed using the
      Kaplan-Meier method. RESULTS: The overall 3-year and 5-year survival rates of 62%
      and 41%, respectively, were not influenced by age, gender, duration of chronic
      hepatitis, serum albumin, prothrombin time ratio, total bilirubin, gamma-glutamyl
      transferase, hepatitis B surface antigen, antihepatitis C virus, HCC size, HCC
      ultrasound pattern, HCC histologic or cytologic grading, greatest spleen
      dimension, esophageal varices, or ascites. Levels of alpha-fetoprotein (AFP) > 14
      ng/mL (P < 0.006), alanine aminotransferase > 75 IU/L (P < 0.04), and aspartate
      aminotransferase > 80 IU/L (P < 0.009) and platelet count < 92 x 10(9)/L (P <
      0.02) before treatment were independent predictors of decreased survival. Among
      post-treatment parameters, AFP levels 6 months after PEI > 13.3 ng/mL (P < 0.003)
      and HCC recurrence in another segment of the liver (P < 0.04) were linked to
      decreased survival in univariate analysis. CONCLUSIONS: Among patients with Child
      -Pugh Class A cirrhosis with small uninodular or binodular HCC who are treated
      with multisession PEI, those with elevated serum AFP and transaminase levels and
      low platelet count before treatment are characterized by decreased survival.
      During follow-up, intrahepatic recurrence of the tumor is the main factor
      affecting survival.

PMID- 11443619
TI  - beta-Catenin mutation and overexpression in hepatocellular carcinoma:
      clinicopathologic and prognostic significance.
AB  - BACKGROUND: beta-Catenin has been recognized as a critical member of the Wnt
      signaling pathway, and inappropriate activation of this pathway has been
      implicated in carcinogenesis. METHODS: To determine the clinical significance of
      beta-catenin in hepatocellular carcinoma (HCC), we performed mutational analysis
      at exon 3 of the gene, investigated the subcellular protein expression, and
      analyzed their clinicopathologic and prognostic significance in 60 patients with
      resected primary HCC. RESULTS: By direct DNA sequencing, somatic mutations of the
      beta-catenin gene were detected in 7 (12%) HCCs. All the mutations were found at
      the region (exon 3) responsible for phosphorylation and ubiquitination, therefore
      likely to result in stabilization of free cytoplasmic beta-catenin. Nuclear
      accumulation of the beta-catenin protein, similar to the response to the Wnt
      signal, was found in 10 (17%) HCCs and was closely associated with gene mutation
      (P < 0.001). In the remaining cases, nonnuclear type overexpression, that is,
      overexpression in the cytoplasm and/or cytoplasmic membrane, was observed in 31
      (62%) HCCs, thus suggesting that the mechanisms leading to beta-catenin
      overexpression may be heterogeneous. HCCs with a nonnuclear type of beta-catenin
      overexpression were more frequently larger than 5 cm in diameter (P = 0.022) and
      had poorer cellular differentiation (P = 0.037), and the patients had
      significantly shorter disease-free survival lengths (P = 0.041). Review of the
      data from previous studies in HCC showed that beta-catenin mutations were more
      frequent in HCV-associated HCC than in HBV-associated ones. CONCLUSIONS: beta
      catenin mutation and deregulation may play an important role in
      hepatocarcinogenesis. Nonnuclear type beta-catenin overexpression appeared to
      have pathologic and prognostic significance.

PMID- 11443620
TI  - Sequential combination chemotherapy in patients with advanced nonsmall cell lung
      carcinoma: carboplatin and gemcitabine followed by paclitaxel.
AB  - BACKGROUND: The objective of this Phase II study was to evaluate the concept of
      sequential chemotherapy in the treatment of patients with advanced nonsmall cell
      lung carcinoma (NSCLC) by the administration of carboplatin plus gemcitabine
      followed by of paclitaxel. METHODS: Patients with Stage IIIB (pleural effusion)
      or Stage IV NSCLC and a Southwest Oncology Group (SWOG) performance status (PS)
      of 0--2 were eligible. Therapy consisted of three cycles of carboplatin (area
      under the concentration-time curve = 5.5 mg/mL per minute) on Day 1 and
      gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days followed by three cycles
      of paclitaxel 225 mg/m(2) every 21 days. RESULTS: Of the 37 eligible patients,
      81% had Stage IV disease, and 27% had a PS of 2; all were assessable for survival
      and toxicity; 32 patients were assessable for response. After treatment with
      carboplatin plus gemcitabine, there were no complete responses (CRs) and eight
      partial responses (PRs) (response rate [RR], 25%; 95% confidence interval [95%
      CI], 11--43%). The best overall response was two CRs and eight PRs (RR, 31%; 95%
      CI, 16--50%). The median survival time was 9.5 months, the 1-year survival rate
      was 36% (95% CI, 26--44%), the 2-year survival rate was 11% (95% CI, 3--25%), and
      the median time to disease progression was 4.9 months. The median survivals were
      11.2 months for patients with a PS of 0--1 and 6.4 months for patients with a PS
      of 2. Noncumulative, reversible thrombocytopenia was the principal toxicity with
      carboplatin/gemcitabine therapy. Paclitaxel therapy was well tolerated, and
      moderate (Grade 3) neutropenia was the primary toxic effect. One cardiac death
      occurred, possibly related to paclitaxel. CONCLUSIONS: This study is the first to
      evaluate planned sequential chemotherapy in patients with NSCLC. Carboplatin plus
      gemcitabine followed by paclitaxel was well tolerated and resulted in promising
      survival in this patient population. This pilot experience forms the basis for an
      ongoing SWOG trial. Cancer 2001;92:146-52. Published 2001 American Cancer
      Society.

PMID- 11443621
TI  - Early lung cancer action project: initial findings on repeat screenings.
AB  - BACKGROUND: The Early Lung Cancer Action Project (ELCAP) was designed to evaluate
      the usefulness of annual computed tomography (CT) screening for lung carcinoma.
      With the baseline results having been reported previously, the focus of the
      current study was on the early results of the repeat screenings. METHODS: A
      cohort of 1000 high-risk individuals was recruited for baseline and annual repeat
      CT screening. At last follow-up, a total of 1184 annual repeat screenings had
      been performed. A positive result from the screening test was defined as newly
      detected, one to six noncalcified pulmonary nodules with interim growth. The
      diagnostic workup of the individuals was guided by recommendations supplied by
      the ELCAP investigators to the collaborating clinicians. RESULTS: Of the 1184
      repeat CT screenings, the test result was positive in 30 (2.5%). In 2 of these 30
      cases, the individual died (of an unrelated cause) before diagnostic workup and
      the nodule(s) resolved in another 12 individuals. In the remaining 16
      individuals, the absence of further growth was documented by repeat CT in 8
      individuals and further growth was documented in the remaining 8 individuals. All
      eight individuals with further nodular growth underwent biopsy and malignancy was
      diagnosed in seven. Six of these seven malignancies were nonsmall cell carcinomas
      (five of which were Stage IA and one of which was Stage IIIA) and the one small
      cell carcinoma was found to be of limited stage. The median size dimension of
      these malignancies was 8 mm. In another two subjects, symptoms prompted the
      interim diagnosis of lung carcinoma. Neither of these malignancies was nodule
      associated but rather were endobronchial; one was a Stage IIB nonsmall cell
      carcinoma and the other was a small cell carcinoma of limited stage. CONCLUSIONS:
      False-positive screening test results are uncommon and usually manageable without
      biopsy; compared with no screening, such screenings permit diagnosis at
      substantially earlier and thus more curable stages. Annual repetition of CT
      screening is sufficient to minimize symptom-prompted interim diagnoses of nodule
      associated malignancies.

PMID- 11443622
TI  - Emergence of increased cerebral metastasis after high-dose preoperative
      radiotherapy with chemotherapy in patients with locally advanced nonsmall cell
      lung carcinoma.
AB  - BACKGROUND: In recent years, combined modality induction therapy has defined a
      new standard of care in the treatment of patients with American Joint Committee
      on Cancer (AJCC) Stage III nonsmall cell lung carcinoma, providing improved local
      control and improved disease-free survival. However, the majority of Stage III
      patients still die of recurrent disease. METHODS: Forty-two consecutive patients
      with AJCC Stage IIIA/IIIB nonsmall cell lung carcinoma (NSCLC) who were
      undergoing induction chemoradiotherapy followed by surgical resection of the
      primary NSCLC tumor between December 1, 1987 and September 1, 1999 were analyzed
      for resectability, survival, and patterns of disease failure. These patients
      received cisplatin (60 mg/m(2)) on Days 1 and 22 and etoposide (100 mg/m(2)) on
      Days 1, 2, and 3, and Days 22, 23, and 24 together with 5940 centigrays (cGy) of
      radiation in 180-cGy fractions delivered over 6 weeks. RESULTS: Thirty-one of the
      42 patients (74%) underwent surgical resection of the primary lung tumor and
      mediastinal lymph nodes after chemoradiotherapy. No surgical deaths were
      reported. The median survival of these 31 patients was 52 months. The 5-year
      survival estimate using the Kaplan-Meier method was 49.9%. The local control rate
      was 80%. The incidence of distant metastases other than in the brain was reduced.
      The most frequently involved site of isolated first recurrence was the brain. The
      median time to brain recurrence was 7.5 months from the time of surgical
      resection. All brain metastases were detected within 2 years. CONCLUSIONS: The
      high incidence of isolated brain metastasis after induction chemoradiotherapy and
      curative resection and their response to treatment suggest that routine scans of
      the brain may be indicated in the follow-up of patients with locally advanced
      NSCLC.

PMID- 11443623
TI  - Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact
      on prognosis and on neoangiogenesis.
AB  - BACKGROUND: Hypoxia-inducible factor (HIF)1 alpha is considered to play a key
      role in the adaptation of cells to hypoxia by stimulating angiogenesis via
      regulation of vascular endothelial growth factor and by metabolic adaptation to
      O(2) deprivation. METHODS: Expression of HIF-1 alpha protein and p53 was
      investigated by immunohistochemistry in 51 specimens of supratentorial pure
      oligodendrogliomas. Microvessels density (MVD) was determined by anti-CD34
      immunostaining. The influence of HIF-1 alpha expression on survival was
      investigated using univariate and multivariate analysis. RESULTS: Strong
      expression of HIF-1 alpha was observed in 12 (23.5%) specimens, moderate in 21
      (41.2%) specimens, and weak in 8 (15.7%) cases, and no expression was found in 10
      samples (19.6%). There was no correlation of HIF-1 alpha expression with
      histologic grading (P = 0.428, Mann-Whitney test). Hypoxia-inducible factor-1
      alpha expression and MVD showed a strong correlation (P < 0.001, r = 0.735,
      Spearman coefficient of correlation). Overexpression of p53 was observed in only
      two cases. Patients with strong or moderate expression of HIF-1 alpha had a
      significantly shorter overall survival rate compared with those with low or no
      expression in univariate (P = 0.0434; log-rank test) and multivariate analysis (P
      = 0.0187). CONCLUSIONS: Overexpression of HIF-1 alpha indicates a diminished
      prognosis in oligodendrogliomas, independent of p53 status. This finding may be
      explained by the strong vascularization of these tumors that prevents hypoxia and
      allows O(2) diffusion and henceforth tumor progression.

PMID- 11443624
TI  - Increased risk of soft tissue sarcoma after radiotherapy in women with breast
      carcinoma.
AB  - BACKGROUND: Numerous studies to date have suggested an association between
      radiation exposure and the development of soft tissue sarcoma. The current study
      was performed to quantify the risk of soft tissue sarcoma in the vicinity of
      previously irradiated anatomic regions in women with breast carcinoma. METHODS:
      In this population-based, retrospective cohort study, 194,798 women who were
      diagnosed with invasive breast carcinoma (exclusive of those with distant
      metastasis) between 1973--1995 were identified, and subsequent soft tissue
      sarcoma cases utilizing the data from the Surveillance, Epidemiology, and End
      Results Program (SEER) were ascertained. Poisson regression analysis was used to
      calculate age standardized incidence ratios (SIR) and to model the influence of
      radiotherapy (RT) on the relative risk (RR) between the RT and non-RT cohorts.
      RESULTS: A total of 54 women in the RT cohort and 81 women in the non-RT cohort
      subsequently developed soft tissue sarcoma. In the RT cohort, the SIR was 26.2
      (95% confidence interval [95% CI], 16.5--41.4) for angiosarcoma and was 2.5 (95%
      CI, 1.8--3.5) for other sarcomas; in the non-RT cohort, the SIRs were 2.1 (95%
      CI, 1.0--4.4) and 1.3 (95% CI, 1.0--1.7), respectively. The RT cohort
      demonstrated a higher risk of developing both angiosarcoma (RR: 15.9; 95% CI, 6.6
      -38.1) and other sarcomas (RR: 2.2; 95% CI, 1.4--3.3) compared with the non-RT
      cohort, and the largest increase was observed in the chest wall/breast. The
      elevated RR was significant even within 5 years of RT, but it reached a maximum
      between 5--10 years. CONCLUSIONS: The risk of soft tissue sarcoma, especially
      angiosarcoma, was elevated after RT in women with breast carcinoma.

PMID- 11443625
TI  - Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?
AB  - BACKGROUND: The CDH1 gene encodes E-cadherin, an epithelial cell adhesion
      molecule. Germline CDH1 mutations recently were identified in families with
      hereditary diffuse gastric carcinoma in a pattern suggestive of autosomal
      dominant inheritance with incomplete penetrance. METHODS: The proband was a woman
      age 47 years with a strong family history of diffuse gastric carcinoma. A
      germline E-cadherin gene mutation was identified in this patient, her brother,
      and three first cousins. All five family members underwent endoscopic
      evaluations, which were negative for malignancy, and elected to undergo a
      prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy. RESULTS:
      Pathologic examination of the proband's stomach revealed several microscopic foci
      of intramucosal signet ring cell adenocarcinoma in the cardia and proximal
      gastric body. Postgastrectomy specimens from the proband's brother and three
      first cousins all showed intramucosal signet ring cell adenocarcinoma in various
      regions of the stomach. Immunoperoxidase studies performed on gastric tissue from
      these five patients demonstrated diminished or absent E-cadherin reactivity in
      the cancerous mucosa. CONCLUSIONS: Although total gastrectomy was performed as a
      prophylactic intervention, occult gastric carcinoma was discovered in all five
      patients. Thus, total gastrectomy should be curative for gastric carcinoma in
      these patients. Based on their successful outcomes and the lack of efficacious
      surveillance methods for diffuse gastric carcinoma, prophylactic total
      gastrectomy may be the management of choice for germline E-cadherin gene mutation
      carriers. However, prophylactic total gastrectomy should be undertaken cautiously
      because the procedure may be associated with considerable morbidity.

PMID- 11443626
TI  - Relation between cyclooxygenase-2 expression and tumor invasiveness and patient
      survival in transitional cell carcinoma of the urinary bladder.
AB  - BACKGROUND: Expression of the inducible form of cyclooxygenase (COX)-2 is known
      to correlate with development of transitional cell carcinoma (TCC) of the human
      urinary bladder. However, the clinical significance of COX-2 expression with
      respect to clinicopathologic findings and patient survival is unknown. METHODS:
      COX-2 expression was examined immunohistochemically in tumor tissues obtained
      from 108 patients who underwent radical cystectomy for TCCs, without knowledge of
      clinicopathologic findings. Correlation between COX-2 expression and
      clinicopathologic findings and patient survival was determined. RESULTS: COX-2
      expression was detected in 34 of 108 (31%) tumors but in none of 10 normal
      uroepithelial samples. Univariate logistic regression analysis showed a
      significant correlation between COX-2 expression and local invasion, infiltration
      pattern, lymphatic invasion, and venous invasion. However, multivariate logistic
      regression analysis revealed that only local invasion correlated significantly
      with COX-2 expression (P = 0.047). Cox proportional hazards regression analysis
      showed that both local invasion (P = 0.008) and lymph node metastasis (P = 0.001)
      were independent prognostic factors; however, COX-2 expression (P = 0.16) was
      not. CONCLUSIONS: The authors showed that COX-2 overexpression plays a role in
      development and invasion of TCCs, but not prognosis of patients with TCC. COX-2
      inhibitors may be useful for chemoprevention of TCCs and treatment of invasive
      disease.

PMID- 11443627
TI  - Gemcitabine modulation of alkylator therapy: a phase I trial of escalating
      gemcitabine added to fixed doses of ifosfamide and doxorubicin.
AB  - BACKGROUND: The authors investigated the maximum tolerated dose (MTD) and dose
      limiting toxicity (DLT) associated with the addition of a biomodulating dose of
      gemcitabine to an established regimen of ifosfamide and doxorubicin as part of a
      program to explore the potential of low-dose gemcitabine to modulate the activity
      of alkylating agents. METHODS: A Phase I trial was carried out in a population of
      patients with bladder or pelvic carcinoma for whom no standard therapy was
      available. Doses of ifosfamide and doxorubicin were held fixed at 2 g/m(2) for 4
      days and 20 mg/m(2) for 3 days, respectively. Gemcitabine was given on Day 2 and
      Day 4 at doses of 90 mg/m(2), 150 mg/m(2), and 200 mg/m(2) per dose. RESULTS: A
      total of 18 patients received 53 courses of therapy. Myelosuppression was dose
      limiting. Nonhematologic toxicity also was significant, with 10 of 18 patients
      experiencing toxicity of Grade 3 or greater. For previously untreated patients
      with an intact performance status, the MTD for gemcitabine in this context was at
      least 150 mg/m(2) per dose. According to an intent-to-treat analysis, 11 of 18
      patients demonstrated a clinically significant response to this regimen.
      CONCLUSIONS: The regimen of ifosfamide and doxorubicin with the addition of
      gemcitabine was significantly toxic but has promising activity. Based on the
      observed activity and the generally reversible nature of the toxicity, the
      authors have initiated a Phase II trial of this regimen in patients with
      untreated, metastatic urothelial carcinoma.

PMID- 11443628
TI  - Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional
      cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40
      patients.
AB  - BACKGROUND: The prognosis of patients with human immunodeficiency virus (HIV)
      related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete
      response (CR) rate, approximately 50% of these patients die from progressive
      lymphoma. METHODS: From November 1994 to April 2000, the authors treated 40
      patients with resistant or recurrent HIV-related NHL with a 96-hour continuous
      intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin
      (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). RESULTS: The median
      number of cycles administered was two (range, one to six cycles). A CR was
      documented in 4 of 40 patients (10%), and a partial remission (PR) was documented
      in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+
      months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median
      survival was 4 months (range, < 1--33 months), and the median survival for
      responding patients was 10 months. CONCLUSIONS: The current data confirm that
      infusional cyclophosphamide, doxorubicin, and etoposide is active in patients
      with refractory or recurrent HIV-related NHL. However, the median survival of
      these patients remains poor, and the other innovative approaches should be used.

PMID- 11443629
TI  - Colony specificity in a social call of mouse lemurs (Microcebus ssp.).
AB  - Nocturnal primate species are often difficult to discriminate by gross visual
      bodily characteristics. This is also true for the world's smallest primate taxon,
      the Malagasy mouse lemurs. Recent findings imply that this taxon contains sibling
      species that can be diagnosed noninvasively by their species-specific
      advertisement call. We used comparative bioacoustics in order to explore
      variation of this call type and to assess species status of three European
      colonies. Acoustic variation was compared within and between colonies as well as
      with known species-specific differences. It was further related to morphological
      and genetic variations to investigate in how far it covaries with them. Results
      show that acoustic and genetic differences revealed by random amplified
      polymorphic DNA (RAPD) fingerprinting separated colonies reliably, but were on a
      different level than known species-specific differences. A Mantel test showed
      that acoustic differences were weakly correlated to genetic, but not to
      morphological differences. Our study is the first to reveal that both acoustic
      signaling and genetics clearly establish the species status for nocturnal primate
      populations. It also suggests that acoustic traits change at a more obvious and
      rapid pace than morphology in isolated populations, and may be used as an
      indication of conditions that may favor the evolution of subspecies.

PMID- 11443630
TI  - Benefits of polyspecific associations for the Goeldi's monkey (Callimico
      goeldii).
AB  - Polyspecific associations are an important component of Callimico goeldii
      behavior and ecology. On average, Callimico goeldii was found in proximity to or
      in vocal contact with Saguinus troops (S. fuscicollis and S. labiatus) during 53%
      of all time intervals sampled. Polyspecific associations varied considerably
      between seasons, however, with association rates peaking during the wet-season
      month of February (89%) and declining in the dry season, with the lowest rate
      (13%) in July. The primary benefits of associations appear to be an increased use
      of the lower and middle canopy, and an increase in feeding behaviors during the
      wet season. Thus, Callimico goeldii appear to benefit most from associations
      during the wet season when fruits are its principal food source. Fruits are eaten
      more in the forest canopy than in the understory; thus, an increase in height use
      likely permits an increase in the fruit resources on which Callimico goeldii can
      forage and feed. In addition, Saguinus groups, with their smaller home ranges,
      are likely to be more knowledgeable than Callimico goeldii about the location and
      abundance of ripe fruits in their home ranges. Thus, Callimico goeldii may
      parasitize Saguinus for their fruit knowledge by following them through their
      ranges. In the dry season, limited dietary overlap between Callimico goeldii and
      Saguinus groups is likely to make associations less beneficial for Callimico
      goeldii as they adopt different foraging and ranging strategies.

PMID- 11443631
TI  - Parental failure in captive cotton-top tamarins (Saguinus Oedipus).
AB  - Several New World monkey species experience high rates of infant mortality in
      captivity, and parental failure in the form of infant neglect and abuse is often
      regarded as one of the leading causes of this problem. We explored a large
      archival database to assess environmental, familial, and biological variables
      identified as significant for parental success in previous studies of captive
      tamarins, through several generations and across several dozen pedigrees. Using a
      stepwise multiple regression analysis we developed a model including the fewest
      variables able to identify statistically significant predictors of infant
      outcome. We found that seven independent variables could predict infant outcome
      in the colony. The most important appeared to be the presence of helpers with
      whom parents could share infant carrying. Mother's experience and litter size
      were two other variables that contributed to a significant extent to explaining
      parental failure. Moreover, the model showed that there is a measurable
      contribution to infant outcome due to the health status of both parents. Finally,
      we found a distinct role for mothers and fathers, and that parental failure
      follows different patterns for abuse and rejection.

PMID- 11443632
TI  - Detection of antibodies to selected human pathogens among wild and pet macaques
      (Macaca tonkeana) in Sulawesi, Indonesia.
AB  - Human-to-primate disease transmission can potentially cause significant morbidity
      and mortality among wild primate populations and thus constitutes an important
      conservation issue. Our cross-sectional study examines serological evidence of
      exposure to human pathogens among wild and pet macaques in Sulawesi. Serum
      samples taken from 11 pet and 15 wild macaques (Macaca tonkeana) were analyzed
      for antibodies to a panel of viruses commonly encountered in human populations.
      Antibodies to measles, influenza A, and parainfluenza 1 were detected in sera of
      both pet and wild macaques. Antibodies to parainfluenza 2 and 3 were found in the
      sera of wild macaques only. Possible routes of exposure, as well as implications
      for conservation are discussed.

PMID- 11443633
TI  - The diagnosis of hairy cell leukemia can be established by flow cytometric
      analysis of peripheral blood, even in patients with low levels of circulating
      malignant cells.
AB  - The diagnosis of hairy cell leukemia (HCL) has traditionally been based on
      microscopic means. Immunophenotypic analysis of peripheral blood by flow
      cytometry is not widely recognized as a method for diagnosing HCL, perhaps due to
      the expectation of low yield of neoplastic cells in patients who are
      characteristically leukopenic. The abnormal coexpression of CD103, CD25, and
      intense CD11c and CD20 on monotypic, slightly large B-lymphocytes has previously
      been shown to be highly characteristic of HCL. We wished to determine if this
      pattern was valuable in the diagnosis of HCL in leukopenic patients with low
      levels of neoplastic cells in the peripheral blood. The abnormal immunophenotype
      above was observed in 25 peripheral blood specimens from patients with
      unexplained cytopenias or suspected lymphoproliferative processes. Ten of the 25
      blood samples exhibited this abnormal phenotype in less than 5% of circulating
      leukocytes (ranging from <1% to 4%). All 10 patients had other manifestations of
      HCL, including cytopenias (mean white blood cell count, 1.8 x 10(3)/mm(3);
      hemoglobin, 11.0 gm/dl; platelets, 74 x 10(3)/mm(3)), splenomegaly, and typical
      bone marrow morphologic changes. Eight of the 10 patients achieved an excellent
      response to one course of 2-CDA, with significant improvement of cytopenias (mean
      white blood cell count: 5.3 x 10(3)/mm(3); hemoglobin: 14.4 g/dl; platelets: 181
      x 10(3)/mm(3)) and regression of splenomegaly. One patient had a partial response
      to alpha interferon and a subsequent complete response to 2-CDA, and one died
      during treatment. In conclusion, flow cytometric immunophenotyping of peripheral
      blood is capable of detecting low levels of circulating malignant cells in HCL,
      even in leukopenic patients. As such, it can be a very useful, non-invasive tool
      in the diagnosis of this disorder.

PMID- 11443634
TI  - Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic
      transplantation for advanced myelodysplastic syndrome and acute myelogenous
      leukemia.
AB  - Sixty-two adults underwent marrow or blood stem cell transplantation from an HLA
      matched related donor using high-dose thiotepa, busulfan, and cyclophosphamide
      (TBC) as the preparative regimen for treatment of advanced myelodysplastic
      syndrome (MDS) (refractory anemia with excess blasts with or without
      transformation) or acute myelogenous leukemia (AML) past first remission. All
      evaluable patients engrafted and had complete donor chimerism. A grade 3-4
      regimen-related toxicity occurred in eight (13%) patients, and a diagnosis of MDS
      was the only independent risk factor for grade 3-4 regimen-related toxicity
      (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19%.
      Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4,
      P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis
      reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients,
      the three-year relapse rate was 43% (95% CI, 28%-58%). Refractoriness to
      conventional induction chemotherapy prior to transplantation was an independent
      risk factor for relapse (hazard ratio 10.8, P = 0.02). Three-year survival was
      26% (95% CI, 14%-37%); survival rates were 29% for those transplanted for AML in
      second remission, 31% transplanted for AML in relapse, and 17% with MDS, and
      there were no independent risk factors for survival. TBC is an active preparative
      regimen for advanced AML. Patients with advanced MDS appeared to have a higher
      risk of toxicity and early mortality, and alternative preparative regimens should
      be considered for these patients.

PMID- 11443635
TI  - Infiltration of cervical lymph nodes by B- and T-cell non-Hodgkin's lymphoma and
      Hodgkin's lymphoma: preliminary ultrasonic findings.
AB  - Ultrasonography has been used in the evaluation of enlarged lymph nodes in
      patients with malignant lymphoma, which comprises a variety of histopathological
      subtypes. We assessed ultrasonic findings of infiltration in cervical lymph nodes
      of 47 patients with previously untreated malignant lymphoma and correlated them
      with histopathological subtypes. Common findings among various histopathological
      subtypes were hypoechoic masses, spot and/or line echoes, involvement of multiple
      nodes, and posterior enhancement. In addition, each histopathological subtype
      showed characteristic findings: Hodgkin's disease had a contour with a lobular
      pattern (9/10 cases), septum-like echo (9/10 cases), and tubular structure (9/10
      cases) in the internal echo, reflecting histopathologically fibrous connective
      tissue surrounding lymph nodes and small vessels. In B-cell lymphoma, there was
      characteristically a tendency for lymph node fusion (19/28 cases) and spot and/or
      line echoes (17/28 cases), reflecting histopathological replacement and
      destruction of the structure of lymph node and capsule by proliferation of
      lymphocytes. These findings were strengthened in diffuse large B-cell lymphoma. T
      cell lymphoma was distinguished from other types of lymphoma by the presence of a
      hilum-like echo (6/9 cases), reflecting histopathologically prominent
      vascularization in lymph nodes accompanied by a dilated hilum area. In summary,
      this preliminary study suggests that ultrasonic findings of infiltration of
      cervical lymph nodes in major subtypes of malignant lymphoma could reflect
      characteristic histopathological structures, therefore providing information
      helpful for differentiating them.

PMID- 11443636
TI  - Therapeutic choices for patients with hemophilia and high-titer inhibitors.
AB  - Effective treatment of bleeding episodes in hemophilia with high titer inhibitors
      (HTI) remains a challenge, despite the fact that the therapeutic armamentarium
      has expanded considerably over the past few years. Treatment safety has improved
      with the availability of porcine factor VIII (FVIII) and bypassing products such
      as recombinant factor VIIa (rFVIIa), and plasma-derived activated Prothrombin
      Complex Concentrates (aPCCs) that are virally inactivated. The major drawbacks of
      rFVIIa and aPCCs are their unpredictable hemostatic effect, lack of laboratory
      assays to monitor efficacy and dosing frequency, and the risk of thrombosis. The
      proceedings of a one-day workshop of physicians who specialized in treating
      patients with hemophilia held in Vienna on May 13, 2000 have been summarized. In
      making a decision regarding the choice of product, physicians often consider the
      type of bleeding episode (life or limb threatening), age of the patient, volume
      of the reconstituted product, previous exposure to plasma derived products, cost,
      efficacy, and safety. For plasma naive patients, to achieve rapid hemostasis a
      majority of the panelists used porcine FVIII (for patients who lack porcine
      inhibitory antibodies) or rFVIIa. For patients previously treated with plasma
      derived factors, in addition to the above concentrates, aPCCs were recommended.
      Although no data exists regarding safety and efficacy, switching products was
      routinely practiced either because of availability or cost. Furthermore, the
      panelists were uncertain about the efficacy of bypassing agents in the prevention
      of joint disease in inhibitor patients. The workshop participants felt that
      future research offers the best solution to resolve some of the dilemmas faced by
      clinicians and may help individualise treatment in a hemophilia patient with a
      high titer inhibitor.

PMID- 11443637
TI  - Laboratory method to study mutational effects on human erythrocyte spectrin
      tetramerization.
AB  - We have developed a laboratory method combining a random mutagenesis method and a
      yeast two-hybrid system to study effects of mutation on human erythrocyte
      spectrin tetramerization. A PCR-based procedure was used to generate random
      mutations in DNA fragments of the first 55 residues of alpha-spectrin. Each of
      the DNA fragments from random mutagenesis was fused with a DNA fragment of native
      spectrin consisting of residues 56 to 368 to give a DNA fragment of the first 368
      residues in alpha-spectrin. The alpha-spectrin DNA fragment and a DNA fragment
      containing the last 449 residues in beta-spectrin were introduced into the yeast
      two-hybrid system for rapid screening of alpha- and beta-spectrin interaction.
      Yeast colonies with interacting alpha- and beta-peptides were blue, and those
      with non-interacting alpha- and beta-peptides were white. Six single amino acid
      mutations (R27G, Y35N, F38S, L49H, Y53N, and Y53C) and a double amino acid
      mutation (K16M, I24N) were identified from 8 white colonies, but no mutations
      were found in the DNA fragments of 14 blue colonies. Thus this simple laboratory
      method allows us to study effects of mutation on interactions of alpha- and beta
      spectrin at the tetramerization site.

PMID- 11443638
TI  - Successful treatment of severe aplastic anemia associated with human parvovirus
      B19 and Epstein-Barr virus in a healthy subject with allo-BMT.
AB  - Several reports have noted pancytopenia associated with Human parvovirus B19
      (PVB19) or Ebstein-Barr virus (EBV) infections in patients who have no history of
      immunodeficiency. To our knowledge, we report the first case of severe aplastic
      anemia associated with both EBV and PVB19 infections in a previously healthy 22
      year-old man. He was admitted to our hematology service due to anemia and
      thrombocytopenia. He had no symptoms or signs of infections of these viruses. His
      bone marrow biopsy revealed a hypocellular marrow. Specific IgM and IgG
      antibodies to EBV and PVB19 were elevated. EBV and PVB19 virus genomes were
      detected by PCR in the bone marrow nucleated cells and the peripheral blood
      lymphocytes. Two months after treatment with prednisone, acyclovir, and
      intravenous immune globulin (IVIg), the genomes of both these viruses
      disappeared. However, his transfusion requirement for platelet suspensions and
      packed red blood cells persisted. The patient underwent allogeneic bone marrow
      transplant (allo-BMT) and has had an enduring complete hematological response for
      8 months.

PMID- 11443639
TI  - Report of three cases of circulating heparin-like anticoagulants.
AB  - Clinically significant endogenous circulating heparin-like anticoagulant activity
      has been associated with hematological malignancies, liver damage, and other
      pathological conditions. The source of high plasma concentrations of endogenous
      heparin-like anticoagulants is poorly understood. We report three cases of
      circulating heparin-like anticoagulants in three patients with hematological
      malignancies: CLL, multiple myeloma, and T-prolymphocytic leukemia. The severity
      of bleeding in our patients ranged from severe epistaxis and deep-site hematoma
      to bleeding of biopsy site and occasional ecchymosis.

PMID- 11443640
TI  - Massive plasmocytosis due to methimazole-induced bone marrow toxicity.
AB  - Pancytopenia is a rare complication of the thionamide therapy reported secondary
      to aplastic anemia, the bone marrow being invariably hypocellular. We present a
      case of a 16-year-old female with Graves' disease who presented with massive bone
      marrow plasmocytosis mimicking multiple myeloma. The patient had already been on
      methimazole for a month when she was admitted to the Pediatric Unit with the
      diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed
      hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI
      was discontinued and the patient was started on broad-spectrum antibiotics,
      dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo
      normocellular marrow, with remaining 6% plasma cells. Myeloma screen was
      negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months
      after patient's discharge, her clinical condition, CBC, and bone marrow remained
      normal. To our knowledge this is the first report of pancytopenia due to MMI,
      where the usual hypoplasia found is replaced by massive plasmocytosis.

PMID- 11443641
TI  - Antibody against platelet membrane glycoprotein VI in a patient with systemic
      lupus erythematosus.
AB  - Platelet-collagen interaction is important in primary hemostasis and collagen
      receptors on the platelet surface include membrane glycoprotein (GP) Ia/IIa and
      VI. Platelets from a 47-year-old woman with systemic lupus erythematosus (SLE)
      and a mild bleeding symptom showed a defective collagen-induced aggregation and
      an impaired adhesion to collagen surface. The patient's platelets had a markedly
      decreased content of GPVI. The patient had an antibody against GPVI in serum and
      the patient's plasma induced aggregation and release reaction of normal
      platelets. These findings indicate that GPVI is an important receptor for
      collagen on the platelet surface, and that anti-GPVI antibody activates the
      platelets, resulting in aggregation. This is the first documented case of SLE who
      acquired a platelet-aggregating anti-GPVI antibody.

PMID- 11443642
TI  - Management of heparin allergy in pregnancy.
AB  - Thromboembolic disease during pregnancy has traditionally been treated with
      heparin. If heparin cannot be used, then treatment options remain limited.
      Despite the recent availability of new anticoagulation agents, data relating to
      their use during pregnancy is lacking. Hirudin, a relatively new anti-thrombotic
      agent, through animal models has been shown to have a very low transplacental
      transfer, thus making it a candidate drug to be used during pregnancy in case of
      heparin allergy. This report describes a case of heparin allergy in a pregnant
      patient with recurrent DVT that was successfully managed with hirudin and
      coumadin.

PMID- 11443643
TI  - Critical regions for deubiquitinating activity of DUB-2 expressed in T
      lymphocytes.
AB  - Ubiquitin- and proteasome-mediated protein degradation is involved in many
      intracellular processes, including cell cycle regulation, transcriptional
      activation, and signal transduction in all eukaryotes. Novel subfamily members of
      the ubp superfamily, DUB-1 and DUB-2, are known to be immediate-early genes and
      are specifically expressed in B-lymphocytes and T-lymphocytes, respectively. With
      the site-directed mutagenesis in four conserved amino acids (Cys60, Asp133,
      His298, and His307) and a series of deletion in the carboxy-terminal region, we
      demonstrate that these conserved amino acids are critical, but not the C
      terminus, for the deubiquitinating activity of DUB-2.

PMID- 11443644
TI  - Primary granulocytic sarcoma of the nasopharynx.

PMID- 11443645
TI  - Masked deficit of B(12) and folic acid in thalassemia.

PMID- 11443646
TI  - Secondary myelodysplastic syndrome after treatment of prostate cancer with oral
      estramustine.

PMID- 11443647
TI  - Effect of pregnancy on isolated platelet factor 3 (PF3) defect.

PMID- 11443648
TI  - Near-haploidy in myeloid antigen positive childhood acute lymphoblastic leukemia.

PMID- 11443649
TI  - Simvastatin-induced thrombocytopenia.

PMID- 11443650
TI  - Flow cytometric analysis of an expansion paroxysmal nocturnal hemoglobinuria
      (PNH) clone in a patient with bone marrow failure.

PMID- 11443651
TI  - Thalassemia trait or thalassemia intermedia.

PMID- 11443654
TI  - Noncovalent Synthesis Using Hydrogen Bonding.
AB  - Hydrogen bonds are like human beings in the sense that they exhibit typical
      grouplike behavior. As an individual they are feeble, easy to break, and
      sometimes hard to detect. However, when acting together they become much stronger
      and lean on each other. This phenomenon, which in scientific terms is called
      cooperativity, is based on the fact that "1+1 is more than 2". By using this
      principle, chemists have developed a wide variety of chemically stable structures
      that are based on the reversible formation of multiple hydrogen bonds. More than
      20 years of fundamental studies on these phenomena have gradually developed into
      a new discipline within the field of organic synthesis, and is nowadays called
      "noncovalent synthesis". This review describes noncovalent synthesis based on the
      reversible formation of multiple hydrogen bonds. Starting with a thorough
      description of what the "hydrogen bond" really is, it guides the reader through a
      variety of bimolecular and higher order assemblies and exemplifies the general
      principles that determine their stability. Special focus is given to reversible
      capsules based on hydrogen-bonding interactions that exhibit interesting
      encapsulation phenomena. Furthermore, the role of hydrogen-bond formation in self
      replicating processes is actively discussed, and finally the review briefly
      summarizes the development of novel materials (nanotubes, liquid crystals,
      polymers, etc.) and principles (dynamic libraries) that recently have emanated
      from this intriguing field of research.

PMID- 11443656
TI  - Superconductivity in MgB(2) at 39 K-A Sensational and Curious Discovery.

PMID- 11443655
TI  - Alkyl, Silyl, and Phosphane Ligands-Classical Ligands in Nonclassical Bonding
      Modes.
AB  - Alkyl, silyl, and phosphane ligands are amongst the most familiar and ubiquitous
      ligands in organometallic and coordination chemistry. The C, Si, and P donor
      atoms of these ligands are sp(3)-hybridized and the ligands are related to each
      other by the isolobal analogy: (CR(3))(-)&harrcir;(SiR(3))(-)&harrcir;PR(3).
      Herein, we demonstrate that although a number of unusual observations concerning
      the reactivity and bonding of these ligands appears unrelated at first sight,
      they in fact provide offer an exiting and consistent picture that may form the
      basis for new paradigms. The characterization of stable complexes in which alkyl,
      silyl, and phosphane ligands behave as symmetrical bridges confirms that there is
      no inherent thermodynamic instability associated with these bonding situations,
      and, in fact, reactivity studies suggest that these ligands should be able to
      bridge between metal centers in reaction intermediates or transition states.

PMID- 11443657
TI  - RNA Interference: A New Way to Analyze Protein Function.

PMID- 11443658
TI  - First Metallabenzenes and now a Stable Metallabenzyne.

PMID- 11443659
TI  - Unprecedented Seven- and Eight-Connected Lanthanide Coordination Networks This
      work was supported by the Royal Society and the Engineering and Physical Sciences
      Research Council (Royal Society K. C. Wong and EPSRC postdoctoral fellowships to
      D.-L.L.). 

PMID- 11443660
TI  - Working Supramolecular Machines Trapped in Glass and Mounted on a Film Surface We
      thank the National Science Foundation and the Sandia National Laboratories for
      supporting this research. 

PMID- 11443661
TI  - Helical Superstructures of a C(2)-Symmetric Molecule Exhibiting Strong Second
      Harmonic Generation in the Solid-State Financial support from the DST
      (Swarnajayanti Fellowship) and the use of the National Single Crystal
      Diffractometer Facility (funded by the DST at the School of Chemistry, University
      of Hyderabad) are gratefully acknowledged. P.G. thanks the University Grants
      Commission for a senior research fellowship. We thank du Pont Deutschland for a
      generous gift of 1,2-diaminocyclohexane. 

PMID- 11443662
TI  - A New Family of Layered Molybdenum(V) Cobalto-Phosphates Built up of

PMID- 11443663
TI  - The First Inorganic "Tennis Ball" Encapsulating an Anion This work was
      financially supported by a Korean Research Foundation grant (No. 1997-011-D
      00013). 

PMID- 11443664
TI  - Optically Active Seleninic Acids: Optical Resolution and Stability.

PMID- 11443665
TI  - [{]

PMID- 11443666
TI  - A Very Rigid Bis-bispidine Tetraazamacrocycle and Its Unusual Copper(II) Complex
      This work was supported by the Deutsche Forschungsgemeinschaft (DFG).
      Bispidine=3,7-diazabicyclo

PMID- 11443667
TI  - Novel Amide-Based Molecular Knots: Complete Enantiomeric Separation, Chiroptical
      Properties, and Absolute Configuration We would like to thank Prof. F. V. Schurig
      for his advice regarding the separation of the enantiomers. The results reported
      here were, in part, presented in Chamonix (September 2000; W.L.) and in Vienna,
      Tsukuba, Kopenhagen, Bordeaux, and Strasbourg (October-December 2000; F.V.). 

PMID- 11443668
TI  - Synthesis of the First 1,3,4-Triphosphole Complex This work was supported by the
      Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. We thank
      Andreas Weinkauf for measuring the X-ray data. 

PMID- 11443669
TI  - Unexpected Splitting of ansa-Ytterboacene and ansa-Calcoacene: Formation of

PMID- 11443671
TI  - Low-Temperature Selective Catalytic Reduction (SCR) of NO with NH(3) by Using Mn,
      Cr, and Cu Oxides Supported on Hombikat TiO(2) We are grateful to the Ohio Coal
      Development Office (OCDO), Columbus, Ohio, for financial support and for allowing
      us to publish the findings. 

PMID- 11443670
TI  - A New Strategy for Synthesizing Endohedral Metallocenophanes This work was
      supported by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen
      Industrie, and the BASF AG Ludwigshafen. 

PMID- 11443672
TI  - Total Synthesis of Colombiasin A This work was financially supported by the
      National Institutes of Health (USA) and The Skaggs Institute for Chemical
      Biology, postdoctoral fellowships from Bayer AG (to R.K. and W.M.), and grants
      from Abbott, Amgen, ArrayBiopharma, Boehringer-Ingelheim, Glaxo, Hoffmann-La
      Roche, DuPont, Merck, Novartis, Pfizer, and Schering Plough. 

PMID- 11443673
TI  - Reactions of Organoselenenyl Iodides with Thiouracil Drugs: An Enzyme Mimetic
      Study on the Inhibition of Iodothyronine Deiodinase This study was supported by
      the Alexander von Humboldt-Stiftung in the form of a research fellowship to G. M.

PMID- 11443675
TI  - Separation of Enantiomers by Extraction Based on Lipase-Catalyzed Enantiomer
      Selective Fluorous-Phase Labeling This work was supported by the Deutsche
      Forschungsgemeinschaft (grant: TH 562/3-1) and the Fonds der Chemischen
      Industrie. 

PMID- 11443674
TI  - Tuning the Electronic Structure of Halidobis(o-imino-benzosemiquinonato)iron(III)
      Complexes This work was supported by the Fonds der Chemischen Industrie. H. Chun
      thanks the Alexander von Humboldt Foundation for a stipend. 

PMID- 11443676
TI  - A New Type of Doubly Silylamido-Bridged Cyclopentadienyl Group 4 Metal Complexes
      We thank the Direccion General de Ensenanza Superior e Investigacion Cientifica
      (DGESEIC) for financial support of this work (Project PB97-0776). J.C. thanks the
      CAM for a Postgraduate Fellowship. 

PMID- 11443677
TI  - Tetrathiafulvaleno-Annelated Porphyrins We gratefully acknowledge financial
      support from Carlsbergfondet and Bengt Lundquists Minnesfond for a post-doctoral
      position to T. B., the University of Odense for a Ph.D. scholarship to J. O. J.
      and the French Embassy Copenhagen for a travel grant to J. B. We thank HASYLAB at
      DESY, Hamburg for beam time at beam line BW1 and DANSYNC for financial support.
      The gift of Jan Skov Peterson's FORTRAN program LSQREFL is gratefully
      acknowledged. Finally, we thank Prof. K. S. Murray, University of Monash,
      Australia for helpful discussions. 

PMID- 11443678
TI  - Bis(germavinylidene)

PMID- 11443679
TI  - A Synthetic Pore-Mediated Transmembrane Transport of Glutamic Acid This work is
      supported by a grant from the National Institutes of Health (Grant: GM52190). 

PMID- 11443680
TI  - Stereoselective Hydrocyanation of Alkenyl Sulfoxides as a Method to Highly
      Enantiomerically Enriched Compounds with Tertiary and Quaternary Chiral Carbon
      Atoms This work was supported by the Direccion General de Investigacion
      Cientifica y Tecnica (grants BQU 2000-0246 and PB98-0102). 

PMID- 11443681
TI  - Synthesis of a Remarkably Stable Dehydro

PMID- 11443682
TI  - IR-UV Double-Resonance Photodissociation of Nitric Acid (HONO(2)) Viewed as
      Molecular Information Processing This work was supported by the James Franck
      Program for Laser-Matter Interaction. 

PMID- 11443683
TI  - Oxide Addition to a Reactive Polysulfide Flux: Synthesis of K(4)Ba

PMID- 11443684
TI  - Switching a Catalyst System from Ethene Polymerization to Ethene Trimerization
      with a Hemilabile Ancillary Ligand Netherlands Institute for Catalysis Research
      (NIOK) publication RUG 01-04-02. 

PMID- 11443685
TI  - An Insoluble Polymer-Bound Bis-Oxazoline Copper(II) Complex: A Highly Efficient
      Heterogeneous Catalyst for the Enantioselective Mukaiyama Aldol Reaction This
      work was supported by MURST, Universita di Pisa (National Project
      "Stereoselezione in Sintesi Organica, Metodologie ed Applicazioni"), and
      Consiglio Nazionale delle Ricerche (CNR). 

PMID- 11443686
TI  - Self-Assembly of Pyramidal Tetrapalladium Complexes with a Halide at the Apex
      This work was supported by the DGESIC (Project No. MAT99-0971) and the JCyL
      (Project No. VA17/00B). We thank Prof. Odile Eisenstein for very useful
      discussions during her stay as Iberdrola Visiting Professor. 

PMID- 11443687
TI  - Tin-Free Radical Acylation Reactions with Methanesulfonyl Oxime Ether We thank
      the CMDS and the BK21 project for financial support. 

PMID- 11443688
TI  - Cyclodextrin Cavities as Probes for Ligand-Exchange Processes.

PMID- 11443689
TI  - Ruthenium Nitrides: Redox Chemistry and Photolability of the Ru-Nitrido Group
      This work was supported by the "Fonds National Suisse de la Recherche
      Scientifique" (Grant No. 20-61'246.00). 

PMID- 11443691
TI  - A Three-Component Coupling Reaction of Aldehydes, Amines, and Alkynes.

PMID- 11443690
TI  - DFT Calculation of Intermolecular Nuclear Spin-Spin Coupling in van der Waals
      Dimers The authors wish to thank V. G. Malkin and O. L. Malkina for providing the
      deMon-NMR program and for helpful discussions. 

PMID- 11443692
TI  - Unprecedented Detection of Distinct Barriers Involving Formally Enantiotopic
      Substituents: Phenyl Rotation in Solid Diphenyl Sulfoxide Conformational Studies
      by Dynamic NMR. Part 82. For Part 80 see ref. 1a, for Part 81 see ref. 1b. We
      thank J. E. Anderson (University College, London, UK), S. E. Biali (Hebrew
      University, Jerusalem, Israel), R. K. Harris (University of Durham, UK), W. B.
      Jennings (University College, Cork, Ireland), A. Rassat (Ecole Normale
      Superieure, Paris, France) for critical reading of the manuscript, and
      I.Co.C.E.A., CNR, Bologna for access to the 400-MHz and solid-state NMR
      spectroscopy facilities. Financial support was received from MURST (national
      project "Stereoselection in Organic Synthesis") and from the University of
      Bologna (Funds for selected research topics 1999-2001). 

PMID- 11443693
TI  - Exceptionally Long (>/=2.9 A) C-C Bonds between

PMID- 11443694
TI  - Introduction to this issue: the clinician's duty to warn or protect.

PMID- 11443695
TI  - Current analysis of the Tarasoff duty: an evolution towards the limitation of the
      duty to protect.
AB  - In 1976, the Tarasoff case established a new legal duty to protect third parties
      from a psychiatric patient's foreseeable violence. After the Tarasoff case,
      courts expanded the scope and role of a clinician's duty to protect, sometimes in
      novel ways. Later interpretations of Tarasoff began to limit significantly the
      situations in which a duty to protect would attach. Recent Tarasoff-type cases in
      which courts have rejected the clinician's duty to warn suggest that Tarasoff is
      declining in significance. The advent of state statutes that codify the
      establishment and discharge of Tarasoff duty have contributed to a further
      limitation of the duty to protect. Lastly, when faced with the management of
      dangerous patients, we advocate for a thorough, well documented assessment of
      risk of violence as the best means for addressing concern about potential legal
      liability.

PMID- 11443696
TI  - Moral justification for Tarasoff-type warnings and breach of confidentiality: a
      clinician's perspective.
AB  - After brief review of the background and context of the Tarasoff case and its
      impact on clinicians, the author examines the "Tarasoff warning," proposed in the
      1974 Tarasoff opinion, from a moral position, with brief discussion of its
      clinical and risk management dimensions. Moral issues considered include
      confidentiality itself, agency, fiduciary duty, a shift in the victim paradigm,
      the emergency context, a novel risk, and a proposed approach. The dilemma
      presented by the original Tarasoff fact situation is re-examined. The author
      stresses the need for individualized responses to the risks posed by patients.

PMID- 11443697
TI  - To warn and to control: two distinct legal obligations or variations of a single
      duty to protect?
AB  - Prior to the Tarasoff decisions, jurisprudence pertaining to the duty to warn, or
      inform, to prevent violence to third persons, was separate from that pertaining
      to the duty to control to prevent such violence. The Tarasoff Principle
      consolidated preventive obligations in the face of foreseeable violence under a
      single "duty to protect." Even as courts adopted divergent rules for establishing
      foreseeability, many held to a single duty to protect with warnings as one
      possibility for fulfilling this option. Particularly over the past decade, courts
      have again disengaged the duty to warn and the duty to control, each requiring
      different legal predicates to occur. In recent years, courts have upheld or
      rejected a duty to warn, upheld or rejected a duty to control; and several courts
      have, within a single opinion, articulated fundamental distinctions between these
      two separate protective duties.

PMID- 11443698
TI  - Assessing violence risk in Tarasoff situations: a fact-based model of inquiry.
AB  - Although significant advances in risk assessment research and practice have been
      made in recent years, there has not been any analysis in the professional
      literature regarding how and whether the emerging practice recommendations apply
      in Tarasoff-type situations. We suggest that, when faced with a Tarasoff-type
      situation, the appraisal of risk should be guided by a method that is primarily
      fact-based and deductive, rather than by the more inductive risk assessment
      approach for general violence recidivism, which is guided primarily by base rates
      and historical risk factors. We review the principles underlying a fact-based, or
      threat assessment, approach and outline six areas of inquiry that can guide the
      appraisal of risk: A-attitudes that support or facilitate violence, C-capacity, T
      thresholds crossed, I-intent, O-other's reactions, and N-noncompliance with risk
      reduction interventions.

PMID- 11443699
TI  - Clinical training and the duty to protect.
AB  - Given that the duty to protect is now a well established clinical and legal
      expectation, training in professional psychology should assist students in
      developing conceptual models for violence risk assessment and management. This
      report presents a training model incorporating recent advancements in risk
      assessment (such as the assessment of psychopathy), the need for basic legal
      understanding, and knowledge of specific risk management strategies.
      Additionally, academic and internship training programs in Michigan were surveyed
      by telephone about current training patterns. Preliminary results indicated
      program strengths in general awareness and training in risk factors. However, the
      data also suggested a need to formalize a faculty role in risk education, improve
      the training of students in relevant legal information, and establish coherent
      conceptual models of dealing with potential patient violence. It is argued that
      improving training of future professionals in this way will improve clinical
      practice, reduce legal liability, and improve public safety.

PMID- 11443700
TI  - Genetic risk: the new frontier for the duty to warn.
AB  - Mental health professionals usually think of the "duty to warn" in the context of
      mental illness. However, two state appellate courts have endorsed a duty to warn
      when children of a patient may be at risk genetically for acquiring the disease
      of their parents. In these cases, the courts held that a physician's legal
      obligations extended beyond his or her patient to the patient's children. This
      article discusses these cases, as well as issues regarding implementation of such
      a duty and the implications for the physician-patient relationship in a health
      care environment that will be dominated increasingly by genetics issues. The
      article concludes that it is premature to apply a duty to warn to the treatment
      of mental illness and to concerns regarding future criminal behavior.

PMID- 11443701
TI  - Psychologists' perceptions of their duty to protect uninformed sex partners of
      HIV-positive clients.
AB  - The purpose of the present study was to determine whether mental health
      professionals would breach the confidentiality of HIV-infected patients with
      uninformed sex partners, and how any such disclosure would occur. Subjects read
      one of eight vignettes that depicted a patient who refused to disclose his viral
      status. Results revealed a split of opinion about breaching confidentiality and
      about the preferred mode for doing so. Neither diagnosis nor mode of viral
      transmission significantly influenced breaching decisions. Subjects demonstrated
      a high level of AIDS risk knowledge but only a moderate level of legal/ethical
      knowledge. Implications of these findings are discussed.

PMID- 11443702
TI  - Potential erosion of psychotherapist-patient privilege beyond California: dangers
      of "criminalizing" Tarasoff.
AB  - The "dangerous patient exception" to psychotherapist-patient privilege, adopted
      almost a decade before the celebrated case of Tarasoff v. Regents of the
      University of California (1976), was mentioned in a footnote to that decision in
      the context of an analogy. Although intended to permit testimony in civil
      commitment proceedings, this exception has been used to "criminalize" the
      Tarasoff duty in California. California courts eroded the privilege initially
      primarily to permit victims to sue psychotherapists and later to require
      psychotherapists to testify against their patients in criminal proceedings and
      appear to have confused evidentiary privilege and confidentiality. If consistent,
      similar reasoning in California in the future should allow therapists to testify
      against their patients if they were civilly committed in the past for
      dangerousness and attorneys to testify against their clients in criminal cases if
      at some earlier time they believed their clients represented a risk of future
      harm. Although most other jurisdictions may not word their privilege exceptions
      for civil commitment in the same way as California, most states have some type of
      privilege exception for civil commitment that could allow for such an
      interpretation. The United States Supreme Court in Jaffee v. Redmond (1996) found
      a psychotherapist-patient privilege, but stated in a footnote that an exception
      to the privilege would exist if a serious threat of harm to the patient could be
      averted only by means of disclosure by the therapist. Other jurisdictions have
      begun to consider these issues. Rather than being unique to California, similar
      reasoning could lead to the "criminalization" of Tarasoff in other jurisdictions
      and thereby compel therapists outside California to testify against their
      patients in criminal proceedings.

PMID- 11443703
TI  - Parahydrogen-induced polarization in imaging: subsecond (13)C angiography.
AB  - High nuclear spin polarization of (13)C was reached in organic molecules.
      Enhancements of up to 10(4), compared to thermal polarization at 1.5 T, were
      achieved using the parahydrogen-induced polarization technique in combination
      with a field cycling method. While parahydrogen has no net polarization, it has a
      high spin order, which is retained when hydrogen is incorporated into another
      molecule by a chemical reaction. By subjecting this molecule to a sudden change
      of the external magnetic field, the spin order is transferred into net
      polarization. A (13)C angiogram of an animal was generated in less than a second.
      Magn Reson Med 46:1-5, 2001.

PMID- 11443704
TI  - Hyperechoes.
AB  - A novel spin-echo-based refocusing strategy called a hyperecho mechanism is
      introduced by which the full coherence of magnetization submitted to a sequence
      of arbitrary RF pulses can be reinstalled. First implementations illustrate the
      potential of hyperecho formation-especially for Rapid Acquisition with Relaxation
      Enhancement (RARE) imaging, in which the full image intensity can be retrieved
      using a fraction of the RF power of a fully refocused sequence. The contribution
      of stimulated echo pathways to the hyperecho signal leads to an increased signal
      intensity at a given refocusing time for tissues with T(1) > T(2). For identical
      T(2) contrast, longer echo times have to be used. Further possibilities for using
      hyperechoes in gradient-echo sequences and for spin selection are discussed. Magn
      Reson Med 46:6-12, 2001.

PMID- 11443705
TI  - In vivo imaging of the neutron capture therapy agent BSH in mice using (10)B MRI.
AB  - Boron neutron capture therapy (BNCT) is an experimental cancer treatment modality
      requiring the targeting of (10)B-enriched compounds to the tumor, which is then
      irradiated by low-energy neutrons. One of the boron-containing compounds used for
      this purpose is the mercaptoborane Na(2)B(12)H(11)SH (BSH). The first in vivo MR
      images of (10)B-enriched BSH are presented here. BSH, injected into the tail vein
      of mice with implanted M2R melanoma xenografts, was imaged using 3D gradient echo
      (10)B MRI. (10)B NMR spectroscopy, localized mainly to the tumor by virtue of the
      use of a small surface coil, was applied to measure the T(1) (2.9 +/- 0.3 ms) and
      T(2) (1.75 +/- 0.25 ms) values of the (10)B signal. The MRI experiments detected
      levels of about 20 ppm (microg boron / g tissue) at 6 x 6 x 6 mm spatial
      resolution in a total scan time of 16 min. Magn Reson Med 46:13-17, 2001.

PMID- 11443706
TI  - Diffusion tensor imaging of the developing mouse brain.
AB  - It is shown that diffusion tensor MR imaging (DTI) can discretely delineate the
      microstructure of white matter and gray matter in embryonic and early postnatal
      mouse brains based on the existence and orientation of ordered structures. This
      order was found not only in white matter but also in the cortical plate and the
      periventricular zone, which are precursors of the cerebral cortex. This DTI-based
      information could be used to accomplish the automated spatial definition of the
      cortical plate and various axonal tracts. The DTI studies also revealed a
      characteristic evolution of diffusion anisotropy in the cortex of the developing
      brain. This ability to detect changes in the organization of the brain during
      development will greatly enhance morphological studies of transgenic and knockout
      models of cortical dysfunction. Magn Reson Med 46:18-23, 2001.

PMID- 11443707
TI  - 7T vs. 4T: RF power, homogeneity, and signal-to-noise comparison in head images.
AB  - Signal-to-noise ratio (SNR), RF field (B(1)), and RF power requirement for human
      head imaging were examined at 7T and 4T magnetic field strengths. The variation
      in B(1) magnitude was nearly twofold higher at 7T than at 4T ( approximately 42%
      compared to approximately 23%). The power required for a 90 degrees pulse in the
      center of the head at 7T was approximately twice that at 4T. The SNR averaged
      over the brain was at least 1.6 times higher at 7T compared to 4T. These
      experimental results were consistent with calculations performed using a human
      head model and Maxwell's equations. Magn Reson Med 46:24-30, 2001.

PMID- 11443708
TI  - Differential routing of choline in implanted breast cancer and normal organs.
AB  - Choline is an essential nutrient participating as the initial substrate in major
      metabolic pathways. The differential metabolic routing of choline was
      investigated in MCF7 human breast cancer implanted in nude mice and in the
      kidney, liver, and brain of these mice. The distribution of metabolites following
      infusion of [1,2-(13)C]-choline was monitored by (13)C magnetic resonance
      spectroscopy. This infusion led to an 18-fold increase in plasma choline and to
      concomitant changes in the content and distribution of choline metabolites. In
      vivo kinetic studies of the tumor during the infusion demonstrated accumulation
      of choline in the interstitium and intracellular synthesis of phosphocholine. The
      amount of unlabeled choline metabolites was 7.1, 4.1, 3.5, and 1.4 micromol/g in
      the kidney, liver, tumor, and brain, respectively. The variations in the labeled
      metabolites were more pronounced with high amounts in the kidney and liver (8.0
      and 4.3 micromol/g, respectively) and very low amounts in the tumor and brain
      (0.33 and 0.12 micromol/g, respectively). In the kidney and liver, betaine
      (unlabeled and labeled) was the predominant choline metabolite. The dominant
      unlabeled metabolite in breast cancer was phosphocholine and in the brain
      glycerophosphocholine. Magn Reson Med 46:31-38, 2001.

PMID- 11443709
TI  - Alternative 1-(13)C glucose infusion protocols for clinical (13)C MRS
      examinations of the brain.
AB  - Clinical utility of (13)C MRS is limited by cost and long examination times.
      Three 1-(13)C glucose infusion protocols-a high-dose i.v., low-dose i.v., and
      oral administration of 1-(13)C glucose-were compared on a GE 1.5T MR scanner.
      Resolution and sensitivity were sufficient to identify (13)C glucose (1alpha and
      1beta), glutamate (C1-C4), glutamine (C1-C4), aspartate (C2 and C3), lactate,
      alanine, and bicarbonate in brain spectra. The three protocols were efficacious,
      as measured by cerebral enrichment of 1-(13)C glucose (62%, 42%, and 38%) and its
      principal metabolite, 4-(13)C glutamate (13%, 11%, and 16%), respectively.
      Intravenous infusion of 1-(13)C glucose 0.23 g/kg body weight (low dose) provides
      equivalent information at one third the cost of previous regimes. Magn Reson Med
      46:39-48, 2001.

PMID- 11443710
TI  - Time-dependent effects of hormone-deprivation therapy on prostate metabolism as
      detected by combined magnetic resonance imaging and 3D magnetic resonance
      spectroscopic imaging.
AB  - Combined MRI and 3D spectroscopic imaging (MRI/3D-MRSI) was used to study the
      metabolic effects of hormone-deprivation therapy in 65 prostate cancer patients,
      who underwent either short, intermediate, or long-term therapy, compared to 30
      untreated control patients. There was a significant time-dependent loss of the
      prostatic metabolites choline, creatine, citrate, and polyamines during hormone
      deprivation therapy, resulting in the complete loss of all observable metabolites
      (total metabolic atrophy) in 25% of patients on long-term therapy. The amount and
      time-course of metabolite loss during therapy significantly differed for healthy
      and malignant tissues. Citrate levels decreased faster than choline and creatine
      levels during therapy, resulting in an increase in the mean (choline +
      creatine)/citrate ratio with duration of therapy. Due to a loss of all MRSI
      detectable citrate, this ratio could not be used to identify cancer in 69% of
      patients on long-term therapy. In the absence of citrate, however, residual
      prostate cancer could still be detected by elevated choline levels
      (choline/creatine ratio > or =1.5), or the presence of only choline in the proton
      spectrum. The loss of citrate and the presence of total metabolic atrophy
      correlated roughly with decreasing serum prostatic specific antigen levels with
      increasing therapy. In summary, MRI/3D-MRSI provided both a measure of residual
      cancer and a time-course of metabolic response following hormone-deprivation
      therapy. Magn Reson Med 46:49-57, 2001.

PMID- 11443711
TI  - Localized two-dimensional shift correlated MR spectroscopy of human brain.
AB  - A two-dimensional (2D) chemical shift correlated MR spectroscopic (COSY) sequence
      integrated into a new volume localization technique (90 degrees -180 degrees -90
      degrees ) is proposed for whole-body MR spectroscopy (MRS). Using the product
      operator formalism, a theoretical calculation of the volume localization as well
      as the coherence transfer efficiencies in 2D MRS is presented. Phantom model
      solutions were used to test and optimize the efficiency of the proposed sequence.
      A combination of different MRI transmit/receive RF coils was used: a head MRI
      coil and a 3" surface coil receive combined with a body coil transmit. The J
      cross-peaks due to N-acetyl aspartate (NAA), glutamate/glutamine (Glx), myo
      inositol (mI), creatine (Cr), choline (Ch), aspartate (Asp), gamma-aminobutyrate
      (GABA), taurine (Tau), glutathione (GSH), threonine (Thr), and macromolecules
      (MM) were identified. The cross-peak intensities excited by the proposed 2D
      sequence were asymmetric with respect to the diagonal peaks. Localized COSY (L
      COSY) spectra of cerebral prefrontal and occipital gray/white matter regions in
      15 healthy controls are presented. Magn Reson Med 46:58-67, 2001.

PMID- 11443712
TI  - Compartmentation of intracellular water in multicellular tumor spheroids:
      diffusion and relaxation NMR.
AB  - Diffusion and relaxation of water in C6 glioma and MLS human ovarian carcinoma
      spheroids were measured from 1D projections acquired using a 2D diffusion
      relaxation correlation pulse sequence and processed by non-negative least-square
      (NNLS) analysis. Systematic underestimation of I(s) and ADC(s) were observed for
      I(s)/(I(s) + I(f)) < 0.001. In the presence of spheroids, two apparent diffusion
      coefficient (ADC) compartments were observed, where ADC(f), ADC(s), and I(f),
      I(s) are the respective ADCs and signal intensities of the fast and slow
      compartments. These compartments differed also in their T(2) relaxation (ADC(s) =
      0.5-0.74 x 10(-5) cm(2)/s, T(2) = 36-45 ms; and ADC(f) = 2.2-2.8 x 10(-5)
      cm(2)/s, T(2) = 280-316 ms). The two ADC compartments and the slow T(2)
      compartment were consistent with slow exchange. The fast T(2) compartment showed
      a drift with diffusion weighting, suggesting that it represents water exchanging
      between compartments that differ in their ADC and T(2). Both ADC(s) and I(s) were
      markedly attenuated with increasing diffusion time (Delta) for Delta < 100 ms,
      and increased at longer Delta. These results are consistent with restricted
      diffusion and fast relaxation of intracellular water for short diffusion time
      (T(1)' = 46.6 ms), and with predominant extracellular contribution to ADC(s) at
      longer diffusion times. Magn Reson Med 46:68-77, 2001.

PMID- 11443713
TI  - Background suppression using magnetization preparation for contrast-enhanced MR
      projection angiography.
AB  - In contrast-enhanced MR projection angiography, vessel conspicuity is determined
      by the T(1)-weighted signal difference between blood and surrounding tissues. For
      slice-selective excitation pulses, the excitation angle varies across the slice,
      leading to poor saturation of the background signal at the slice edge and
      reducing the blood-background signal difference. This work reports on the use of
      magnetization preparation to enhance the T(1)-weighted contrast between blood and
      background tissue. Applying the prepulse nonselectively reduces the influence of
      the slice profile imperfections of the excitation pulse by keeping the background
      tissue at the slice edge saturated. Analytical calculations and in vitro
      experiments show that a prepulse angle of 110 degrees -130 degrees and a delay
      time of 20-25 ms enhance the contrast between contrast-enhanced blood (T(1) < 50
      ms) and background tissues (T(1) > 200 ms), and improve the slice weighting
      profile. Magnetization preparation is shown to effectively suppress signal from
      background tissue, resulting in a threefold increase of the vessel-to-background
      signal ratio. Magnetization preparation eliminates the need for subtraction at
      the cost of a slight increase in scan time. Possible applications, such as
      projection MRA, detection of contrast arrival, and test-bolus tracking are
      demonstrated in a pig model. Magn Reson Med 46:78-87, 2001.

PMID- 11443714
TI  - High-sensitivity single-shot perfusion-weighted fMRI.
AB  - A method is presented for measurement of perfusion changes during brain
      activation using a single-shot pulsed spin labeling technique. By employing a
      double-inversion labeling strategy, stationary tissue (background) signal was
      suppressed while minimally affecting perfusion sensitivity. This allowed omission
      of the otherwise required reference scan, resulting in twofold-improved temporal
      resolution. The method was applied to visual and motor cortex activation studies
      in humans, and compared to standard FAIR-type perfusion labeling techniques.
      Experiments performed at 1.5T and 3.0T indicate a close to 90% suppression of
      background signal, at a cost of an 11% and 9%, respectively, reduction in
      perfusion signal. Combined with the twofold increase in signal averaging, and a
      reduction in background signal fluctuations, this resulted in a 64% (1.5T, N = 3)
      and a 128% (3T, N = 4) overall improvement in sensitivity for the detection of
      activation-related perfusion changes. Magn Reson Med 46:88-94, 2001. Published
      2001 Wiley-Liss, Inc.

PMID- 11443715
TI  - Rapid measurement of aortic wave velocity: in vivo evaluation.
AB  - A 1D MR sequence has been developed for determining aortic flow wave velocity
      (WV), a metric of arterial compliance, within a single cardiac cycle. Studies
      were carried out on the thoracic aortas of 10 normal volunteers. Correlative WV
      data were also acquired from each subject using a conventional phase-velocity 2D
      mapping technique. Aortic WV in this cohort was found to range from 411 to 714
      cm/s and was highly correlated (R = 0.95) between the two methods. Peak blood
      velocity was also measured using both methods and found to agree closely. The
      reproducibility of WV measurements using the rapid 1D method averaged 7.6%, which
      is comparable or better than that achieved using existing noninvasive techniques.
      Magn Reson Med 46:95-102, 2001.

PMID- 11443716
TI  - Trabecular bone volume fraction mapping by low-resolution MRI.
AB  - Trabecular bone volume fraction (TBVF) is highly associated with the mechanical
      competence of trabecular bone. TBVF is ordinarily measured by histomorphometry
      from bone biopsies or, noninvasively, by means of high-resolution microcomputed
      tomography and, more recently, by micro-MRI. The latter methods require spatial
      resolution sufficient to resolve trabeculae, along with segmentation techniques
      that allow unambiguous assignment of the signal to bone or bone marrow. In this
      article it is shown that TBVF can be measured under low-resolution conditions by
      exploiting the attenuation of the MR signal resulting from fractional occupancy
      of the imaging voxel by bone and bone marrow, provided that a reference signal is
      available from a marrow volume devoid of trabeculation. The method requires
      accurate measurement of apparent proton density, which entails correction for
      various sources of error. Key among these are the spatial nonuniformity in the RF
      field amplitude and effects of the slice profile, which are determined by B(1)
      field mapping and numerical integration of the Bloch equations, respectively. By
      contrast, errors from variations in bone marrow composition (hematopoietic vs.
      fatty) between trabecular and reference site are predicted to be small and
      usually negligible. The method was evaluated in phantoms and in vivo in the
      distal radius and found to be accurate to 1% in marrow volume fraction. Finally,
      in a group of 12 patients of varying skeletal status, TBVF in the calcaneus was
      found to strongly correlate with integral bone mineral density of the lumbar
      vertebrae (r(2) = 0.83, p < 0.0001). The method may fail in large imaging objects
      such as the human trunk at high magnetic field where standing wave and RF
      penetration effects cause intensity variations that cannot be corrected. Magn
      Reson Med 46:103-113, 2001.

PMID- 11443717
TI  - High-resolution fMRI using multislice partial k-space GR-EPI with cubic voxels.
AB  - The premises of this work are: 1) the limit of spatial resolution in fMRI is
      determined by anatomy of the microcirculation; 2) because of cortical gray matter
      tortuosity, fMRI experiments should (in principle) be carried out using cubic
      voxels; and 3) the noise in fMRI experiments is dominated by low-frequency BOLD
      fluctuations that are a consequence of spontaneous neuronal events and are pixel
      wise dependent. A new model is proposed for fMRI contrast which predicts that the
      contrast-to-noise ratio (CNR) tends to be independent of voxel dimensions (in the
      absence of partial voluming of activated tissue), TE, and scanner bandwidth.
      These predictions have been tested at 3 T, and results support the model. Scatter
      plots of fMRI signal intensities and low-frequency fluctuations for activated
      pixels in a finger-tapping paradigm demonstrated a linear relationship between
      signal and noise that was independent of TE. The R(2) value was about 0.9 across
      eight subjects studied. The CNR tended to be constant across pixels within a
      subject but varied across subjects: CNR = 3.2 +/- 1.0. fMRI statistics at 20- and
      40-ms TE values were indistinguishable, and TE values as short as 10 ms were used
      successfully. Robust fMRI data were obtained across all subjects using 1 x 1 x 1
      mm(3) cubic voxels with 10 contiguous slices, although 1.5 x 1.5 x 1.5 mm(3) was
      found to be optimum. Magn Reson Med 46:114-125, 2001.

PMID- 11443718
TI  - Chemical shift imaging with spectrum modeling.
AB  - A new chemical shift imaging technique was developed to efficiently obtain
      separate images for multiple chemical shift peaks from a set of spin-echo
      acquisitions. Information from localized NMR spectroscopy was used to model the
      chemical shift spectrum as sharp peaks with known resonance frequencies but
      unknown amplitudes. Based on this model, a set of spin-echo images with shifted
      180 degrees RF pulses were acquired, in which the magnetization vectors of
      different chemical components were put into different directions. The amplitudes
      of the chemical shift peaks were obtained by solving nonlinear equations in a
      region-growing process. Experimental results on an ethanol phantom as well as a
      subject with silicone breast implants are presented. Magn Reson Med 46:126-130,
      2001.

PMID- 11443719
TI  - Fast T(1) mapping with volume coverage.
AB  - Four different sequences which enable high-resolution, multislice T(1) relaxation
      time mapping are presented. All these sequences are based on the Look-Locker
      method with differences arising from the use of either a saturation-recovery or
      inversion-recovery module prior to data acquisition with a full k-space or banded
      k-space acquisition scheme. The methods were implemented on a standard clinical
      scanner and the accuracy of the T(1) results was evaluated against spectroscopic
      measurements. The accuracy of the T(1) maps validated by phantom imaging
      measurements is around 1% for species which relax with T(1) times that mimic
      gray/white matter (T(1) < or = 1000 ms). Additionally, the inherent multislice,
      multipoint capability of the methods is demonstrated. Finally, in vivo results of
      the human brain obtained using the faster method are presented. The fastest data
      acquisition was achieved with a saturation-recovery, banded k-space method where
      k-space was divided into three segments; an overall acquisition time of around 5
      min (for species with T(1) < or = 1 sec) was achieved for a T(1) map which can,
      in principle, provide whole-brain coverage with a matrix size of 256 x 256 at
      multiple time-points. Magn Reson Med 46:131-140, 2001.

PMID- 11443720
TI  - Theoretical analysis of the effect of imperfect slice profiles on tagging schemes
      for pulsed arterial spin labeling MRI.
AB  - Pulsed arterial spin labeling (ASL) techniques provide a noninvasive method of
      obtaining qualitative and quantitative perfusion images with MRI. ASL techniques
      employ inversion recovery and/or saturation recovery to induce perfusion
      weighting, and thus the performance of these techniques is dependent on the slice
      profiles of the inversion or saturation pulses. This article systematically
      examines through simulations the effects of slice profile imperfections on the
      perfusion signal for nine labeling schemes, including FAIR, FAIRER, and EST
      (UNFAIR). Each sequence is evaluated for quantitative accuracy, suppression of
      stationary signal, and magnitude of perfusion signal. Perfusion effects are
      modeled from a modified Bloch equation and experimentally determined slice
      profiles. The results show that FAIR, FAIRER, and EST have excellent tissue
      suppression. The magnitude of the perfusion signal is comparable for FAIR and
      FAIRER, with EST providing a slightly weaker signal. For quantitative
      measurements, all three methods underestimate the perfusion signal by more than
      20%. Of the additional six ASL techniques examined, only one performed well in
      this model. This method, which combines inversion and saturation recovery, yields
      improved signal accuracy (<15% difference from the theoretical value) and tissue
      suppression similar to that of FAIR and its variants, but has only half the
      signal. Magn Reson Med 46:141-148, 2001.

PMID- 11443721
TI  - Characterization and reduction of the transient response in steady-state MR
      imaging.
AB  - Refocused steady-state free precession (SSFP) imaging sequences have recently
      regained popularity as faster gradient hardware has allowed shorter repetition
      times, thereby reducing SSFP's sensitivity to off-resonance effects. Although
      these sequences offer fast scanning with good signal-to-noise efficiency, the
      "transient response," or time taken to reach a steady-state, can be long compared
      with the total imaging time, particularly when using 2D sequences. This results
      in lost imaging time and has made SSFP difficult to use for real-time and cardiac
      gated applications. A linear-systems analysis of the steady-state and transient
      response for general periodic sequences is shown. The analysis is applied to
      refocused-SSFP sequences to generate a two-stage method of "catalyzing," or
      speeding up the progression to steady-state by first scaling, then directing the
      magnetization. This catalyzing method is compared with previous methods in
      simulations and experimentally. Although the second stage of the method exhibits
      some sensitivity to B(1) variations, our results show that the transient time can
      be significantly reduced, allowing imaging in a shorter total scan time. Magn
      Reson Med 46:149-158, 2001.

PMID- 11443722
TI  - Quantitative model for the interecho time dependence of the CPMG relaxation rate
      in iron-rich gray matter.
AB  - A quantitative model is proposed for computing the dependence on the interecho
      time of the NMR relaxation rate in iron-rich gray matter obtained with a Carr
      Purcell-Meiboom-Gill sequence. The model consists of representing
      oligodendrocytes as identical magnetic spheres arranged in a spatially random
      pattern, and in approximating water diffusion as isotropic and unrestricted.
      Predictions of the model are calculated numerically using a Monte Carlo technique
      and, for the weak field limit, using an analytic formula. The model is shown to
      provide a good fit to experimental measurements of in vitro samples of monkey
      brain at field levels of 1.0 T and 1.5 T. These field levels are not sufficient
      to fully determine the model parameters, but it is argued that this may be
      possible at 3.0 T. The model is potentially of value for multiple-spin-echo MRI
      studies of iron-related neurodegenerative disorders, such as Parkinson's disease.
      In particular, the model can be applied to correlate MRI data with the cellular
      distribution of iron in gray matter. Magn Reson Med 46:159-165, 2001.

PMID- 11443723
TI  - Evaluation of regional pulmonary perfusion using ultrafast magnetic resonance
      imaging.
AB  - An ultrafast MR sequence was used to measure changes in signal intensity during
      the first pass of intravascular contrast through the pulmonary circulation. From
      this, mean transit time, relative blood volume, and relative blood flow were
      calculated. Data were collected in an isogravitational plane in six healthy
      subjects. A slight but significant gradient in transit time was present, with
      faster times at the lung apex. A significant decrease in blood volume, compared
      with the lung base, was also seen in the apex. Significant decreases in blood
      volume and blood flow, compared with central portions of the lung, were seen in
      the lung periphery. Six additional subjects were imaged along a gravitational
      plane. A significant gradient in transit time was seen, with faster transit in
      dependent regions of the lung. MRI is able to evaluate regional differences in
      pulmonary perfusion with high spatial and temporal resolution. Magn Reson Med
      46:166-171, 2001.

PMID- 11443724
TI  - Perfusion imaging using spin-labeling methods: contrast-to-noise comparison in
      functional MRI applications.
AB  - In this study the performance of FLASH imaging with selective inversion
      preparation for functional perfusion studies was investigated. In addition to the
      absolute quantification of perfusion by measurement of the longitudinal
      relaxation times with global (T(1glob)) and selective (T(1sel)) inversion, the
      measurement of absolute (BASE) and relative (FAIR) perfusion increases by
      subtraction of appropriately weighted images was also considered. The subject
      averages of absolute perfusion obtained by the quantitative method were 70.7 +/-
      4.0 ml/100g/min in gray matter, 10.2 +/- 3.4 ml/100g/min in white matter, and
      89.0 +/- 3.1 ml/100g/min in visual cortex. These values, as well as the average
      increase of perfusion due to visual stimulation (44.4 +/- 3.7 ml/100g/min), agree
      well with respective data reported by PET and other MRI studies. However, for
      individual subjects the standard deviations over single ROIs inside the visual
      cortex lay around 100% which prevented the detection of significant activation.
      BASE and FAIR, on the other hand, were able to detect significant activation in
      single subjects. The measured average perfusion increases were 51.7 +/- 6.6
      ml/100g/min and 56.5 +/- 13.8%, respectively. Magn Reson Med 46:172-182, 2001.

PMID- 11443725
TI  - Rapid three-dimensional diffusion MRI facilitates the study of acute stroke in
      mice.
AB  - MRI studies using mouse brain models of ischemia are becoming a valuable tool for
      understanding the mechanism of stroke, since transgenic models are now available.
      However, the small size of the mouse brain and the surgical complexity of
      creating ischemia in mice make it technically challenging to obtain high-quality
      MRI data. Therefore, there are few reports of MRI studies in murine cerebral
      ischemia. In this project a newly developed rapid 3D diffusion-weighted imaging
      (DWI) technique was applied to study experimental stroke in a mouse model of
      reversible middle cerebral artery occlusion (MCAO). Ischemic volumes were
      successfully delineated using this 3D whole-brain imaging technique with high
      spatial (0.34 x 0.5 x 1.0 mm(3) before zero-filling) and temporal (7 min)
      resolution. The 3D observation revealed the characteristic evolution of stroke
      after transient MCAO. There was a temporarily high diffusion constant in the
      cortex during early reperfusion, followed by a secondary energy failure in the
      cortex and caudate-putamen at 6 and 21 h of reperfusion. Magn Reson Med 46:183
      188, 2001.

PMID- 11443726
TI  - External standard method for the in vivo quantification of choline-containing
      compounds in breast tumors by proton MR spectroscopy at 1.5 Tesla.
AB  - Quantification of choline-containing compounds observed with (1)H MRS of breast
      tumors is of interest since such compounds have been linked to malignancy.
      Experiments were performed at 1.5 T with an external standard containing
      phosphocholine for calibration. In phantom studies, good precision was achieved
      after correction for T(1)/T(2) effects. T(2) values for choline were estimated
      for two breast cancer patients. A choline concentration of 2.0 mM was calculated
      for a third patient, a result comparable to in vitro findings. Magn Reson Med
      46:189-192, 2001.

PMID- 11443727
TI  - Improved perfusion quantification in FAIR imaging by offset correction.
AB  - Perfusion quantification using pulsed arterial spin labeling has been shown to be
      sensitive to the RF pulse slice profiles. Therefore, in Flow-sensitive
      Alternating-Inversion Recovery (FAIR) imaging the slice selective (ss) inversion
      slab is usually three to four times thicker than the imaging slice. However, this
      reduces perfusion sensitivity due to the increased transit delay of the incoming
      blood with unperturbed spins. In the present article, the dependence of the
      magnetization on the RF pulse slice profiles is inspected both theoretically and
      experimentally. A perfusion quantification model is presented that allows the use
      of thinner ss inversion slabs by taking into account the offset of RF slice
      profiles between ss and nonselective inversion slabs. This model was tested in
      both phantom and human studies. Magn Reson Med 46:193-197, 2001.

PMID- 11443728
TI  - Artifact due to B(0) fluctuations in fMRI: correction using the k-space central
      line.
AB  - Magnetic resonance experiments require the main magnetic field, B(0), to remain
      very stable. Several external sources, such as moving ferromagnetic objects
      and/or changing electromagnetic fields, can significantly change the value of
      B(0) over time. This work describes an apparent displacement along the phase
      encoding axis caused by a variation in B(0). This artifact was observed in fMRI
      images acquired with EPI. The effect was characterized and tested using an
      immobile phantom. The image displacement motion along the phase-encoding axis
      closely followed the changes in B(0). The phase of the central line in the
      Fourier space was successfully used to correct this artifact. Fluctuations in
      B(0) may result in artifacts that mimic subject head motion, and must be
      appropriately corrected. Magn Reson Med 46:198-201, 2001.

PMID- 11443729
TI  - Cerebral perfusion during anesthesia with fentanyl, isoflurane, or pentobarbital
      in normal rats studied by arterial spin-labeled MRI.
AB  - The influence of anesthetic agents on cerebral blood flow (CBF) was tested in
      normal rats. CBF is quantified with arterial spin-labeled MRI in rats
      anesthetized with either an opiate (fentanyl), a potent inhalation anesthetic
      agent (isoflurane), or a barbiturate (pentobarbital) using doses commonly
      employed in experimental paradigms. CBF values were found to be about 2.5-3 times
      lower in most regions analyzed during anesthesia with either fentanyl (with
      N(2)O/O(2)) or pentobarbital vs. isoflurane (with N(2)O/O(2)), in agreement with
      findings utilizing invasive measurement techniques. CBF was heterogeneous in rats
      anesthetized with isoflurane (with N(2)O/O(2)), but relatively homogeneous in
      rats anesthetized with either fentanyl (with N(2)O/O(2)) or pentobarbital, also
      in agreement with studies using other techniques. Magn Reson Med 46:202-206,
      2001.

PMID- 11443730
TI  - Evidence for further breast cancer susceptibility genes in addition to BRCA1 and
      BRCA2 in a population-based study.
AB  - We used data from a population based series of breast cancer patients to
      investigate the genetic models that can best explain familial breast cancer not
      due to the BRCA1 and BRCA2 genes. The data set consisted of 1,484 women diagnosed
      with breast cancer under age 55 registered in the East Anglia Cancer registry
      between 1991-1996. Blood samples taken from the patients were analysed for
      mutations in BRCA1 and BRCA2. The genetic models were constructed using
      information on breast and ovarian cancer history in first-degree relatives and on
      the mutation status of the index patients. We estimated the simultaneous effects
      of BRCA1, BRCA2, a third hypothetical gene BRCA3, and a polygenic effect. The
      models were assessed by likelihood comparisons and by comparison of the observed
      numbers of mutations and affected relatives with the predicted numbers. BRCA1 and
      BRCA2 could not explain all the familial clustering of breast cancer. The best
      fitting single gene model for BRCA3 was a recessive model with a disease allele
      frequency 24% and penetrance 42% by age 70. However, a polygenic model gave a
      similarly good fit. The estimated population frequencies for BRCA1 and BRCA2
      mutations were similar under both recessive and polygenic models, 0.024 and
      0.041%, respectively. A dominant model for BRCA3 gave a somewhat worse fit,
      although the difference was not significant. The mixed recessive model was
      identical to the recessive model and the mixed dominant very similar to the
      polygenic model. The BRCA3 genetic models were robust to the BRCA1 and BRCA2
      penetrance assumptions. The overall fit of all models was improved when the known
      effects of parity on breast and ovarian cancer risks were included in the model
      in this case a polygenic model fits best. These findings suggest that a number of
      common, low-penetrance genes with additive effects may account for the residual
      non-BRCA1/2 familial aggregation of breast cancer, but Mendelian inheritance of
      an autosomal recessive allele cannot be ruled out.

PMID- 11443731
TI  - Heritability of plasma amyloid beta in typical late-onset Alzheimer's disease
      pedigrees.
AB  - Plasma amyloid beta42 peptide (Abeta42) levels are significantly elevated in all
      genetic forms of early-onset Alzheimer's disease caused by familial Alzheimer's
      disease mutations or Down's syndrome. Moreover, recent studies have determined
      that both plasma Abeta42 and Abeta40 levels are significantly elevated in late
      onset Alzheimer's disease (LOAD) patients, their cognitively normal first-degree
      relatives, and members of typical LOAD families when compared to appropriate
      controls. To determine the magnitude of the genetic component affecting plasma
      Abeta levels, we estimated the heritability of plasma Abeta42 and Abeta40 in 15
      extended, multigenerational LOAD pedigrees, using a variance components method.
      Heritability estimates as high as 73 and 54% were found for plasma Abeta42 and
      Abeta40 levels, respectively. Inclusion of the ApoE epsilon4 dosage as a
      covariate was not found to have a significant effect on the heritability of these
      traits. These results suggest that genetic determinants other than ApoE account
      for a very substantial percentage of the phenotypic variance in plasma Abeta
      levels. The high heritability and the significant elevation of these traits in
      LOAD pedigrees suggest that at least some of the genetic determinants of plasma
      Abeta levels may lead to elevated Abeta and LOAD in these families. Thus, we
      suggest that plasma Abeta levels are quantitative traits that may be excellent
      surrogate markers for use in linkage analysis to identify loci that are important
      in typical LOAD.

PMID- 11443732
TI  - Lod scores for gene mapping in the presence of marker map uncertainty.
AB  - Multipoint lod scores are typically calculated for a grid of locus positions,
      moving the putative disease locus across a fixed map of genetic markers. Changing
      the order of a set of markers and/or the distances between the markers can make a
      substantial difference in the resulting lod score curve and the location and
      height of its maximum. The typical approach of using the best maximum likelihood
      marker map is not easily justified if other marker orders are nearly as likely
      and give substantially different lod score curves. To deal with this problem, we
      propose three weighted multipoint lod score statistics that make use of
      information from all plausible marker orders. In each of these statistics, the
      information conditional on a particular marker order is included in a weighted
      sum, with weight equal to the posterior probability of that order. We evaluate
      the type 1 error rate and power of these three statistics on the basis of results
      from simulated data, and compare these results to those obtained using the best
      maximum likelihood map and the map with the true marker order. We find that the
      lod score based on a weighted sum of maximum likelihoods improves on using only
      the best maximum likelihood map, having a type 1 error rate and power closest to
      that of using the true marker order in the simulation scenarios we considered.

PMID- 11443733
TI  - Multipoint development of the weighted pairwise correlation (WPC) linkage method
      for pedigrees of arbitrary size and application to the analysis of breast cancer
      and alcoholism familial data.
AB  - The weighted pairwise correlation (WPC) method is a simple and powerful model
      free method of linkage analysis that has the advantages of being applicable to
      binary, ordered categorical, quantitative, or censored traits, and to consider
      all pairs of relatives in large pedigrees. The originally implemented approach
      was limited to the use of the identical by state (IBS) information, and we
      recently extended the WPC method to incorporate the identical by descent (IBD)
      information for two-point linkage analysis. Here, we develop a multipoint WPC
      method suitable for pedigrees of arbitrary size and large number of markers. The
      multipoint IBD estimation procedure for relative pairs is based on the efficient
      regression approach developed for pedigrees implemented in SOLAR. A robust and
      fast Monte-Carlo procedure is used to determine reliable P values. Application of
      the method to the 214 pedigrees from the Breast Cancer Linkage Consortium
      provided for the Genetic Analysis Workshop (GAW) 9 shows that multipoint WPC
      statistic values were not far from two-point maximum lod-score values obtained by
      the classical parametric linkage method and were higher than multipoint variance
      component analysis lod-scores obtained with SOLAR. The multipoint WPC method is
      also used to analyze the familial Collaborative Study of the Genetics of
      Alcoholism data on alcoholism released for GAW11. It allows a better
      specification of the linkage results previously obtained within the chromosome 4
      region.

PMID- 11443734
TI  - A general and accurate approach for computing the statistical power of the
      transmission disequilibrium test for complex disease genes.
AB  - Transmission disequilibrium test (TDT) is a nuclear family-based analysis that
      can test linkage in the presence of association. It has gained extensive
      attention in theoretical investigation and in practical application; in both
      cases, the accuracy and generality of the power computation of the TDT are
      crucial. Despite extensive investigations, previous approaches for computing the
      statistical power of the TDT are neither accurate nor general. In this paper, we
      develop a general and highly accurate approach to analytically compute the power
      of the TDT. We compare the results from our approach with those from several
      other recent papers, all against the results obtained from computer simulations.
      We show that the results computed from our approach are more accurate than or at
      least the same as those from other approaches. More importantly, our approach can
      handle various situations, which include (1) families that consist of one or more
      children and that have any configuration of affected and nonaffected sibs; (2)
      families ascertained through the affection status of parent(s); (3) any mixed
      sample with different types of families in (1) and (2); (4) the marker locus is
      not a disease susceptibility locus; and (5) existence of allelic heterogeneity.
      We implement this approach in a user-friendly computer program: TDT Power
      Calculator. Its applications are demonstrated. The approach and the program
      developed here should be significant for theoreticians to accurately investigate
      the statistical power of the TDT in various situations, and for empirical
      geneticists to plan efficient studies using the TDT.

PMID- 11443735
TI  - Consanguinity and the transmission/disequilibrium test for allelic association.
AB  - Consanguineous marriages, usually between first cousins or between uncle and
      niece, are common in certain societies. The transmission/disequilibrium test
      (TDT) compares the transmission from parents to an affected child of alleles at a
      marker locus, and differential transmission indicates linkage and allelic
      association between the marker locus and a disease locus. We investigate the
      consequences for the TDT, as a test for allelic association, of consanguineous
      marriages. For each parental marker mating type, we calculate the frequency of
      each disease mating type, and the associated probability that an offspring is
      affected. We use Bayes' Theorem to estimate the probability that an affected
      child inherits the given allele from a heterozygous parent, then combine our
      results across marker mating types. The effect of consanguineous marriage is
      usually small. For candidate genes, the effects were greater for uncle-niece
      marriages, for rare disease alleles, and for high genotype relative risk. For
      markers, the effects were generally negligible. The Type I error probability of
      the TDT is essentially unchanged by intermarriage, except for a purely recessive
      disease allele. The power of the TDT is increased for a recessive allele and
      decreased for a dominant allele. However, consideration of levels of
      consanguinity that arise in practice indicates that standard power calculations
      for the TDT will usually need only minor modification.

PMID- 11443736
TI  - Lack of desmin results in abortive muscle regeneration and modifications in
      synaptic structure.
AB  - Desmin, a muscle-specific intermediate filament protein, is expressed in all
      muscle tissues. Its absence leads to a multisystemic disorder involving cardiac,
      skeletal, and smooth muscles. In skeletal muscle, structural abnormalities
      include lack of alignment of myofibrils, Z disk streaming, and focal muscle
      degeneration. In this study, we have examined the consequences of an absence of
      desmin on the mechanisms of regeneration and the integrity of the neuromuscular
      junction. The muscles of desmin knock-out and wild-type mice were made to
      regenerate by injecting cardiotoxin and were examined 7 to 42 days following the
      injection. The absence of desmin resulted in a delayed and modified regeneration
      and an accumulation of adipocytes. This was associated with a persistence of
      small diameter muscle fibers containing both N-CAM and developmental myosin
      isoforms. The amount of the slow myosin was increased, whereas there was a
      decrease in the fast isoform in the regenerated muscles of desmin knock-out mice.
      Both regeneration and aging led to the appearance of elongated neuromuscular
      junctions with diffuse acetylcholinesterase staining and a decrease in the
      overall acetylcholinesterase activity in the muscles of these mice. The
      neuromuscular junctions were markedly disorganised and in some cases
      postjunctional folds were absent. We conclude that desmin is essential for
      terminal muscle regeneration, maturation of muscle fibers, and maintaining the
      complex folded structure of the postsynaptic apparatus of the neuromuscular
      junctions.

PMID- 11443737
TI  - Mutagenesis of beta-tubulin cysteine residues in Saccharomyces cerevisiae:
      mutation of cysteine 354 results in cold-stable microtubules.
AB  - Cysteine residues play important roles in the control of tubulin function. To
      determine which of the six cysteine residues in beta-tubulin are critical to
      tubulin function, we mutated the cysteines in Saccharomyces cerevisiae beta
      tubulin individually to alanine and serine residues. Of the twelve mutations,
      only three produced significant effects: C12S, C354A, and C354S. The C12S
      mutation was lethal in the haploid, but the C12A mutation had no observable
      phenotype. Based on interactive views of the electron crystallographic structure
      of tubulin, we suggest that substitution of serine for cysteine at this position
      has a destabilizing effect on the interaction of tubulin with the exchangeable
      GTP. The two C354 mutations, although not lethal, produced dramatic effects on
      microtubules and cellular processes that require microtubules. The C354 mutant
      cells had decreased growth rates, a slowed mitosis, increased resistance to
      benomyl, and impaired nuclear migration and spindle assembly. The C354A mutation
      produced a more severe phenotype than the C354S mutation: the haploid cells had
      chromosome segregation defects, only 50% of cells in a culture were viable, and a
      significant percentage of the cells were misshapened. Cytoplasmic microtubules in
      the C354S and C354A cells were longer than in the control strain and spindle
      structures appeared shorter and thicker. Both cytoplasmic and spindle
      microtubules in the two C354 mutants were extremely stable to cold temperature.
      After 24 h at 4 degrees C, the microtubules were still present and, in fact, very
      long and thick tubulin polymers had formed. Evidence exists to indicate that the
      C354 residue in mammalian tubulin is near the colchicine binding site and the
      electron crystal structure of tubulin places the residue at the interface between
      the alpha- and beta-subunits. The sulfhydryl group is situated in a polar
      environment, which may explain why the alanine mutation is more severe than the
      serine mutation. When the C12S and the two C354 mutations were made in a diploid
      strain, the mutated tubulin was incorporated into microtubules and the resulting
      heterozygotes had phenotypes that were intermediate between those of the mutated
      haploids and the wild-type strains. The results suggest that the C12 and C354
      residues play important roles in the structure and function of tubulin.

PMID- 11443738
TI  - Remodeling of the actin cytoskeleton of target hepatocytes and NK cells during
      induction of apoptosis.
AB  - Natural Killer cells are immune cells that recognize and eliminate altered and
      non-self cells from the circulation. To study the interaction between NK cells
      and target cells, we set up an experimental system consisting of rat Interleukin
      2 activated Natural Killer cells (A-NK cells) and rat hepatocytes with a masked
      Major Histocompatibility Complex (MHC). The masking of the MHC induces
      recognition of the hepatocytes by the NK cells as non-self. We showed that in
      vitro apoptosis is rapidly induced in the hepatocytes [Blom et al., 1999] after
      co-incubation with A-NK cells. Now we describe the morphological changes that
      occur during and after interaction of A-NK cells with hepatocytes. Confocal laser
      scanning microscopy showed that the actin cytoskeleton of the NK cells was
      remodeled during attack of hepatocytes. Some NK cells were in close contact with
      the hepatocytes while others had formed actin-containing dendrites of varying
      length that made contact with the hepatocytes. However, dendrite formation is not
      obligatory for induction of apoptosis because cells that were unable to form
      these did induce FAS-dependent apoptosis in hepatocytes. Apparently both direct
      as well as distant contact resulted in apoptosis. Formation of the dendrites was
      calcium-dependent as EGTA largely prevented it. Importantly, chelation of the
      calcium also suppressed killing of the hepatocytes. Within 1 h after addition of
      the A-NK cells, morphological changes in hepatocytes that are characteristic of
      apoptosis, such as the formation of apoptotic bodies and fragmented nuclei,
      became apparent. Specifically, the actin cytoskeleton of the hepatocytes was
      remodeled resulting in the formation of the apoptotic bodies. Inhibition of
      caspase activity by z-Val-Ala-DL-Asp-fluoromethylketone (100 microM) partly
      protected against the rearrangement of the actin filaments in the hepatocytes.

PMID- 11443739
TI  - Initiation of cell locomotility is a morphogenetic checkpoint in thyroid
      epithelial cells regulated by ERK and PI3-kinase signals.
AB  - Epithelial locomotility is a fundamental determinant of tissue patterning that is
      subject to strict physiological regulation. The current study sought to identify
      cellular signals that initiate cell migration in cultured thyroid epithelial
      cells. Porcine thyroid cells cultured as 3-dimensional follicles convert to 2
      dimensional monolayers when deprived of agents that stimulate cAMP/PKA signaling.
      This morphogenetic event is driven by the activation of cell-on-substrate
      locomotility, providing a convenient assay for events that regulate the
      initiation of locomotion. In this system, the extracellular signal regulated
      kinase (ERK) pathway became activated as follicles converted to monolayer, as
      demonstrated by immunoblotting for activation-specific phosphorylation and
      nuclear accumulation of ERK. Inhibition of ERK activation using the drug PD98059
      effectively prevented cells from beginning to migrate. PD98059 inhibited cell
      spreading, actin filament reorganization and the assembly of focal adhesions,
      cellular events that mediate the initiation of thyroid cell locomotility. Akt
      (PKB) signaling was also activated during follicle-to-monolayer conversion and
      the phosphoinositide 3-kinase (PI3-kinase) inhibitor, wortmannin, also blocked
      the initiation of cell movement. Wortmannin did not, however, block activation of
      ERK signaling. These findings, therefore, identify the ERK and PI3-kinase
      signaling pathways as important stimulators of thyroid cell locomotility. These
      findings are incorporated into a model where the initiation of thyroid cell
      motility constitutes a morphogenetic checkpoint regulated by coordinated changes
      in stimulatory (ERK, PI3-kinase) and tonic inhibitory (cAMP/PKA) signaling
      pathways.

PMID- 11443740
TI  - Interaction of elongation factor 1alpha from Zea mays (ZmEF-1alpha) with F-actin
      and interplay with the maize actin severing protein, ZmADF3.
AB  - EF-1alpha is an abundant eukaryotic protein whose principle function appears to
      be to bind aminoacyl-tRNA to the ribosome. However, it is also known that EF
      1alpha from other sources binds both microtubules and microfilaments. We report
      the expression of Zea mays EF-1alpha (ZmEF-1alpha) in bacteria and that this
      protein has similar actin-binding properties as other EF-1alpha members. ZmEF
      1alpha bundles actin filaments at low pH (6.5) and inhibits the addition of
      monomer at both filament ends, possibly as a consequence. ZmEF-1alpha binds actin
      filaments at all pH values tested (pH 6.0-8.0), indicating that one actin binding
      site is not pH sensitive. One of the actin-binding sites was determined to reside
      within domain I (1-223) of ZmEF-1alpha, but this domain did not affect the
      kinetics of polymerisation. We show that the bundling activity of ZmEF-1alpha is
      modulated by ZmADF3 a (a Zea mays ADF/cofilin), an actin filament severing
      protein, in vitro. Bundling of actin filaments caused by ZmEF-1alpha was enhanced
      in the presence of ZmADF3. The pH-dependent activities of both proteins in vitro
      suggests that they may work together to respond to temporal and spatial
      intracellular pH changes to regulate the pattern of the growth of plant cells.

PMID- 11443742
TI  - AJCC stage groupings for head and neck cancer: should we look at alternatives? A
      report of the Head and Neck Sites Task Force.

PMID- 11443743
TI  - A comparison of published head and neck stage groupings in carcinomas of the oral
      cavity.
AB  - BACKGROUND: The combination of T, N, and M classifications into stage groupings
      is meant to facilitate a number of activities, including the estimation of
      prognosis and the comparison of therapeutic interventions among similar groups of
      cases. We tested the UICC/AJCC 5th edition stage grouping and seven other TNM
      based groupings proposed for head and neck cancer for their ability to meet these
      expectations in a specific site: carcinomas of the oral cavity. METHODS: We
      defined four criteria to assess each grouping scheme: (1) the subgroups defined
      by T, N, and M that make up a given group within a grouping scheme have similar
      survival rates (hazard consistency); (2) the survival rates differ among the
      groups (hazard discrimination); (3) the prediction of cure is high (outcome
      prediction); and (4) the distribution of patients among the groups is balanced.
      We identified or derived a measure for each criterion, and the findings were
      summarized by use of a scoring system. The range of scores was from 0 (best) to 7
      (worst). The data are population based from a prospectively gathered series in
      Southern Norway, with 556 patients diagnosed from 1983 through 1995. Clinical
      stage assignment was used, and the outcome of interest was cause-specific
      survival. RESULTS: Summary scores across the eight schemes ranged from 1.66 for
      TANIS-3 to 6.50 for UICC/AJCC-5. The TANIS-7 staging scheme performed best on the
      hazard consistency criterion. The Kiricuta scheme performed best on the hazard
      discrimination criterion. Synderman predicted outcome best overall and Berg
      produced the most balanced distribution of cases among its groups. CONCLUSIONS:
      UICC/AJCC stage groupings were defined without empirical investigation. When
      tested, this scheme did not perform as well as any of seven empirically derived
      schemes we evaluated. Our results suggest that the usefulness of the TNM system
      could be enhanced by optimizing the design of stage groupings through empirical
      investigation.

PMID- 11443744
TI  - Unusual T- and T/NK- cell non-Hodgkin's lymphoma of the larynx: a diagnostic
      challenge for clinicians and pathologists.
AB  - BACKGROUND: Lymphomas of T-cell and T/natural killer (T/NK)-cell types rarely
      involve the larynx. Early symptoms are subtle and nonspecific, and confirmation
      of the diagnosis is often difficult. Because of the rarity of this disease
      entity, the optimal management remains controversial. METHODS: The case records
      of patients with the diagnosis of lymphoma involving the larynx were
      retrospectively reviewed. Details of the pathologic condition, the difficulties
      in diagnosis, and treatment were presented. RESULTS: One case of T-cell lymphoma
      (Lennert's lymphoma subtype) and two cases of T/NK-cell lymphomas involving the
      larynx were presented. The diagnoses were all difficult to establish. All three
      patients received either multiagent chemotherapy or radiotherapy as the first
      line treatment. They all died of the disease within 32 months of diagnosis.
      CONCLUSIONS: T- and T/NK-cell non-Hodgkin's lymphoma of the larynx is a
      diagnostic challenge for clinicians and pathologists. Conventional chemotherapy
      or radiotherapy has not been effective. A more aggressive therapy should be
      considered.

PMID- 11443745
TI  - Association of p53 and BCL-2 expression with Epstein-Barr virus infection in the
      cancers of head and neck.
AB  - BACKGROUND: Reports that have both evaluated the site-specific Epstein-Barr virus
      (EBV) infection and compared it with the expression of the EBV-related proto
      oncogenes and tumor suppressor genes in the various cancers of head and neck are
      scarce. METHODS: Thirty-eight nasopharyngeal carcinoma (NPC) cases, 32
      oropharyngeal or hypopharyngeal carcinoma (OPC/HPC) cases, and 93 laryngeal
      carcinoma (LC) cases were evaluated with in situ hybridization on EBV-encoded
      small RNA (EBER) and immunohistochemical assessments of the p53, bcl-2, and
      epidermal growth factor receptor (EGFR) by use of formalin-fixed paraffin
      embedded tissue array slides. RESULTS: The expression of viral EBERs was observed
      in more than two thirds (71.1%) of the NPC cases. In contrast, only 1 case of OPC
      and none of the HPC or LC cases exhibited EBV positivity. In the nonkeratinizing
      NPC, the EBV positivity was significantly associated with both frequent p53
      overexpression (p =.033) and bcl-2 expression (p =.001). In the EBV-positive
      nonkeratinizing NPC, a correlation between p53 overexpression and the tumor
      infiltration lymphocyte (TIL) density was noted (p =.012). CONCLUSIONS: A site
      specific expression of viral EBER was demonstrated in the head and neck cancers,
      which suggests an important role for both p53 and bcl-2 in the carcinogenesis of
      an EBV-infected NPC. The correlation between p53 overexpression and the TIL
      density in the EBV-infected NPC suggests that the product of a lymphoepithelial
      interaction, such as A20, can induce a dysfunctional p53 protein.

PMID- 11443746
TI  - The use of brush cytology and directed biopsies for the detection of
      nasopharyngeal carcinoma and precursor lesions.
AB  - BACKGROUND: It has been proposed that nasopharyngeal carcinoma (NPC) has an early
      noninvasive stage, designated nasopharyngeal intraepithelial neoplasia (NPIN).
      Hence, the detection and treatment of NPIN will prevent NPC from developing, and
      this would be similar to the strategies used for cervical cancer prevention. We
      wanted to ascertain the feasibility of using a brush sampler to collect cells for
      the cytologic diagnosis of NPIN and NPC. If successful, the technique could be
      used as a screening test in endemic areas. METHODS: A disposable sampler
      (Uterobrush) was used to collect nasopharyngeal mucosal brushings from 546
      patients for cytologic examination. After this, most patients had biopsies, and
      this allowed histologic-cytologic correlation to be undertaken. RESULTS: In 528
      patients (96.7%) there were satisfactory cytologic and biopsy specimens for
      evaluation. There were 149 cases with positive histology and 103 had positive
      cytology (specificity was 100% and the sensitivity was 69.1%). One case of NPC
      with concurrent NPIN was seen among the biopsy specimens, but no case of NPIN was
      detected cytologically. CONCLUSIONS: The cytologic pickup of NPC was
      substantially lower than that obtained on biopsy. More importantly, NPIN was
      uncommon. Therefore, a screening test that depends on the collection of cells for
      the microscopic diagnosis of NPIN and NPC is unlikely to have a major impact on
      the incidence of NPC. Furthermore, obtaining a good cytologic specimen from the
      nasopharynx is not simple, and this further limits this technique for mass
      screening purposes. The concept of a cytologic test for NPC, similar to the Pap
      test for the prevention of uterine cervix cancer, has still to be realized.

PMID- 11443747
TI  - Clinical relevance of Fas (APO-1/CD95) expression in laryngeal squamous cell
      carcinoma.
AB  - BACKGROUND: Expression of Fas receptors renders tumor cells potentially
      susceptible to the host immune system. In squamous cell carcinomas of the head
      and neck, Fas has recently been found to be down-regulated in some cases; its
      prognostic value and correlation with clinicopathologic parameters, however, is
      yet to be delineated. METHODS: Paraffin-embedded specimens of 88 primary
      laryngeal squamous cell carcinomas were investigated for Fas protein expression
      by immunohistochemistry. Apoptotic tumor cells were visualized using the nick end
      labeling method. To assess the immunologic reaction to the neoplasm, the
      intensity of lymphoplasmocytic stroma reaction was determined. The mean follow-up
      time amounted to 45.9 months (range, 1-144 months). RESULTS: In tumor-adjacent
      normal mucosa and in most well-differentiated tumors, Fas expression was
      restricted to basal and parabasal cell layers. A diffuse pattern of staining
      reactions predominated in high-grade lesions (p <.001). The degree of Fas
      expression revealed a positive relationship with the intensity of
      lymphoplasmocytic stroma reaction (p =.002) but was unrelated to
      clinicopathologic parameters and to apoptotic rates of tumors. Neither Fas nor
      the lymphoplasmocytic stroma reaction had any impact on patient survival.
      CONCLUSIONS: Up-regulation of cell surface Fas expression in laryngeal carcinoma
      seems to have a stimulatory effect on the immune cell infiltration of the stromal
      tissue. Its lack of clinical relevance might be due to an inhibition of
      intracellular Fas signal transduction, which represents a frequent strategy of
      tumor cells to escape Fas-mediated apoptosis.

PMID- 11443748
TI  - Surgical treatment of squamous cell carcinoma of the base of tongue.
AB  - INTRODUCTION: Squamous cell carcinoma (SSC) of the tongue base has historically
      been shown to be associated with a poor prognosis. We reviewed our experience
      with primary surgery followed by postoperative radiation therapy (XRT) to
      determine the impact of our treatment protocols on outcome. METHODS: We
      retrospectively reviewed the records of all patients presenting to the University
      of Pittsburgh with previously untreated SSC of the tongue base between 1980-1997.
      Patients who were treated nonoperatively were excluded from analysis. Surgical
      excision of the primary was performed with ipsilateral neck dissection. The
      contralateral neck was dissected when the primary lesion was located in the
      midline or for clinically positive contralateral neck nodes. Postoperatively,
      most patients (93%) received XRT to the primary site and neck. Adjuvant
      chemotherapy was offered if histologic signs of aggressive behavior were
      identified (multiple nodes or extracapsular spread). RESULTS: Of 87 patients
      identified, 39 (45%) were initially seen with T1 or T2 tumors. Seventy-nine
      patients (91%) were initially seen with stage III or IV disease. Contralateral
      neck dissection was performed in 36 patients (41%). Metastatic disease was
      demonstrated in 84% of ipsilateral neck nodes and in 47% of contralateral neck
      nodes. Occult metastases were found in 61% of clinically N0 necks. Local
      recurrence occurred in 5 patients, regional recurrence occurred in 12 patients,
      and distant metastases developed in 22 patients. Overall and disease-specific
      survival rates at 5 years for all patients were 49% and 56%, respectively. The 5
      year disease-specific survival rates for stage I, stage II, stage III, and stage
      IV disease were 100%, 86%, 62%, and 48%. The 5-year disease-specific survival
      rate was 88% for T1 lesions, 64% for T2 lesions, 58% for T3 lesions, and 30% for
      T4 lesions (p <.05, log-rank test). CONCLUSIONS: Surgical treatment of SCC of the
      tongue base is highly effective in achieving local disease control and disease
      free survival for early lesions. Because both functional outcome and survival are
      poor after surgical treatment of advanced lesions, we now offer brachytherapy
      with XRT or participation in a combined chemoradiation protocol rather than
      primary surgical therapy to patients with advanced disease. Prospective studies
      are needed to compare the effect of these organ-preserving therapies with
      traditional combined surgery and XRT to determine the effect on functional
      outcome and quality of life.

PMID- 11443749
TI  - Accelerated hyperfractionated irradiation for advanced head and neck cancer:
      effect of shortening the median treatment duration by 13 days.
AB  - BACKGROUND AND PURPOSE: Optimal treatment duration of altered fractionation
      schedules in head and neck cancer is still undefined. A retrospective study on
      local tumor control, survival, and complications of accelerated hyperfractionated
      irradiation in head and neck cancer was undertaken to investigate whether there
      was an advantage in further shortening overall time from 6.5 weeks. METHODS: Four
      hundred nineteen consecutive male patients treated with radiation alone for cure
      1987-1998 were analyzed. Patients with stage I, or treated also with
      brachytherapy implants or chemotherapy, were excluded. Treatment with accelerated
      hyperfractionation was performed twice daily, at a median of 1.6 Gy/fraction, to
      a total median dose of 68 Gy in 39 days. The patient population was divided into
      two groups: those with < or =39 days overall treatment time (group A, n = 227;
      median, 33 days) and those with >39 days (group B, n = 192; median, 46 days).
      Group A received a significant median tumor dose reduction of 7% compared with
      group B. RESULTS: The 7-year actuarial local control (LC) rates were 59% and 48%
      for groups A and B, respectively (p =.02). The actuarial LC rates for T1-2
      patients were 79% and 74% at 7 years for groups A and B, respectively (p = NS).
      Similarly, for T3-4 patients, they were 47% and 35% (p =.02), respectively. The 7
      year actuarial disease-free survival (DFS) rates for groups A and B were 39% and
      26% (p =.01), respectively. For stage II patients, DFS was 62% and 60% at 7 years
      (p = NS) for groups A and B, respectively. And similarly, for stage III-IV
      patients, DFS was 33% and 20% (p =.04), respectively, at 7 years. LC and DFS
      rates at 7 years for T4 and stage IV patients, respectively, were significantly
      improved in group A. Cox regression analyses for LC showed that both T stage and
      overall time were significant prognostic factors. Similarly, UICC clinical stage
      and overall time were significant prognostic factors for DFS. There was no
      difference in acute morbidity between the two groups: 3% of patients in both
      groups required tube or parenteral feeding. The 7-year actuarial probability of
      RTOG/EORTC grades 3-5 late effects was 15% and 13%, respectively, for each group
      (p = NS). CONCLUSIONS: This study, with the limitations of a retrospective study,
      has shown a significant improvement in local tumor control and disease-free
      survival, in patients treated with shorter overall treatment times (median, 33
      days) with an accelerated hyperfractionated irradiation schedule compared with
      those treated with a median duration of 46 days. No significant enhancement of
      acute reactions and late morbidity were observed with the shorter schedule.

PMID- 11443750
TI  - Validation of the RTOG recursive partitioning classification for head and neck
      tumors.
AB  - BACKGROUND: We previously demonstrated that a mathematical technique called
      recursive partitioning analysis (RPA), when applied to the Radiation Therapy
      Oncology Group Head and Neck Cancer database, created rules that formed subgroups
      ("classes") having unique outcomes. We sought to learn if the application of RPA
      derived rules to a new head and neck database would create classes that were
      similarly associated with outcome and thereby validate this technique. METHODS:
      The rules derived from recursive partitioning analysis of the previous database
      were used to subgroup an independent, new head and neck cancer database (RTOG 85
      27), created as part of a phase III trial of the hypoxic-cell radiosensitizer,
      Etanidazole. The resulting classes were compared with each other and with the
      classes formed from the previous database. RESULTS: The rules derived by RPA from
      our previous database correctly grouped the tumors in the new database into
      unique classes of similar outcome. RPA could successfully use either survival or
      local-regional control of disease as the measure of outcome. As judged by
      comparison of the 95% confidence intervals, the outcome of the classes in the new
      database is essentially indistinguishable from the outcome of the classes in the
      previous database. CONCLUSION: RPA-derived rules provide a reliable method to
      assort head and neck tumors into unique classes that are predictive of outcome.
      These rules can be successfully applied to new databases that were not used in
      the creation of the rules and thereby validate the methodology.

PMID- 11443751
TI  - Concomitant twice-a-day radiotherapy and chemotherapy in unresectable head and
      neck cancer patients: A long-term quality of life analysis.
AB  - BACKGROUND: The purpose of this study is to make a comparative analysis between
      acute toxicity with late toxicity. This study is based upon a French quality of
      life (QoL) questionnaire in a cohort of advanced head and neck (H&N) cancer
      patients treated by concomitant twice-a-day continuous radiotherapy with no
      acceleration and chemotherapy with cisplatin and 5-fluorouracil. METHODS: From
      September 1992 to November 1997, a prospective data bank of 91 patients was
      constituted. In November 1999, 31 patients were still alive and followed for more
      than 3 years. All patients had stage IV strictly unresectable squamous cell
      carcinoma of oropharynx or hypopharynx. A French specific H&N cancer QoL
      questionnaire was used at the end of radiotherapy and at the last date of follow
      up of each patient (during 1999). p values reflect comparison of percentages
      obtained at the end of treatment with percentages at long-term follow-up.
      Statistical analysis was performed using chi(2) test (p <.05 considered as
      significant). Percentages obtained by the QoL questionnaire correspond to
      moderate-severe problems only. RESULTS: Twenty-nine of 31 (94%) patients
      participated in the QoL study. Acute treatment toxicities were severe with
      declines in virtually all QoL and functional domains. Globally, with an average
      long-term follow-up of 4.5 years (range 3-7 years after treatment), there is a
      statistical improvement in the following symptoms: dry mouth and sticky saliva
      (97% versus 55%, p <.05); tasting problems (35% versus 21%, not significant);
      swallowing problems (77% versus 36%, p <.05); and H&N pain (86% versus 9%, p
      <.05). Financial problems were not improved (21% versus 14%, not significant),
      and psychological problems (59% versus 5%) were statistically significant.
      Fourteen of 29 (48%) patients were drinking and 8 of 29 (28%) were smoking at
      long-term follow-up; at the diagnosis they were 86% and 90%, respectively. At
      long-term follow-up 22 of 29 presented good or very good QoL, and 25 of 29 said
      they had improved their initial QoL. CONCLUSION: The interest of twice-a-day
      radiotherapy with concomitant chemotherapy is to increase total radiotherapy
      equivalent dose without increasing late toxicity and also to improve locoregional
      control, survival, and long-term QoL/effectiveness ratio. Best supportive care is
      recommended to obtain both good QoL and cancer control in a long-term follow-up.

PMID- 11443752
TI  - Genomic instability in head and neck cancer patients.
AB  - BACKGROUND: In the normal host, there are a variety of cellular systems that
      ensure the accurate replication and repair of DNA. Recent evidence suggests that
      there are individual variations in the ability to preserve the genome. Certain
      individuals have defects in these checkpoints and have an inherent genomic
      instability. They are susceptible to the accumulation of DNA damage and are prone
      to carcinogenesis. This article examines the role of genomic instability in the
      development of head and neck cancer. RESULTS: Patients with either the
      chromosomal instability syndromes or the Li-Fraumeni syndrome have marked defects
      in either DNA repair or apoptosis. These patients are prone to have head and neck
      neoplasms develop. Head and neck cancer patients also have a diminished ability
      to repair DNA damage compared with the "normal" population. Abnormalities have
      been identified in mutagen sensitivity, the expression of DNA mismatch repair
      enzymes, the expression of p53, and telomerase activity when head and neck cancer
      patients are compared with controls. CONCLUSION: Subpopulations exist who have
      increased genomic instability. These individuals are at an increased risk for the
      accumulation of DNA mutations and the development of head and neck cancer. More
      research is needed to identify specific mechanisms of genomic instability and to
      further define the importance of this phenomenon.

PMID- 11443753
TI  - Calcifying epithelial odontogenic (Pindborg) tumor with malignant transformation
      and metastatic spread.
AB  - BACKGROUND: Pindborg tumors (calcifying epithelial odontogenic tumors) are
      uncommon neoplasms of odontogenic origin most often located in the posterior
      mandible. First described in detail in 1955 by Pindborg, these tumors are
      considered benign but can be locally aggressive in nature, with recurrence rates
      of 10% to 15% reported. The malignant form of this tumor is exceedingly rare.
      METHODS: We describe the case of a 64-year-old woman initially treated for a
      painful infected left mandibular third molar. The patient underwent extraction of
      the tooth and excision of an associated soft tissue component. Subsequent
      histologic review identified a Pindborg tumor of the left posterior mandible.
      RESULTS: After initial excision, this tumor recurred twice, with the recurrences
      exhibiting a progression to a malignant Pindborg tumor (odontogenic carcinoma)
      with vascular invasion and spread to a cervical lymph node. Further treatment
      involved radical surgery and adjuvant radiotherapy. At last review 12 months
      after treatment, the patient was disease free. CONCLUSIONS: This article
      describes only the second case of odontogenic carcinoma. The transformation from
      benign to malignant histologic findings has not previously been documented in
      this tumor. The salient clinical features of this case are presented along with
      supportive pathologic and radiologic evidence.

PMID- 11443754
TI  - Strategies for influencing outcomes in pre-ESRD and ESRD patients.

PMID- 11443755
TI  - Protein restriction in the pre-end-stage renal disease (ESRD) patient: who, when,
      how, and the effect on subsequent ESRD outcome.
AB  - The protein and energy requirements of patients with chronic renal failure are
      similar to those of healthy subjects, and evidence indicates that both nephrotic
      and nonnephrotic chronic renal failure patients can activate normal homeostatic
      responses allowing them to maintain lean body mass when dietary protein intake is
      restricted. The benefits of low protein (and phosphorus) diets include the
      amelioration of uremic symptoms and some of its metabolic complications, and
      possibly slowing the rate of progression of renal failure. Moreover, there is no
      evidence that the use of low protein diets (LPD) in the predialysis period
      results in worse outcomes once dialysis is initiated. When LPD are prescribed,
      patients should be monitored to assess dietary compliance and to ensure
      nutritional adequacy. Recent evidence that nutritional indices of patients with
      progressive chronic renal failure declines when they consume unrestricted diets
      should not be interpreted as justification against the use of LPD. Rather, it is
      a compelling argument to institute dietary therapy to minimize complications of
      renal failure while maintaining nutritional status. Finally, the use of LPD is
      compatible with "timely" initiation of dialysis in accordance with recommended
      guidelines.

PMID- 11443756
TI  - Incremental dialysis.
AB  - The National Kidney Foundation-Dialysis Outcome Quality Initiative Peritoneal
      Dialysis Adequacy Clinical Practice Guideline 1 and Appendix A offered the first
      formal in-depth discussion of the concept of incremental dialysis (1). The
      context of the work group's concern was that it is paradoxical that we
      nephrologists have focused on optimizing urea clearance for end-stage renal
      disease patients, but not in pre-end-stage renal disease patients. Because so
      much evidence from the collective peritoneal dialysis experience suggested that a
      weekly Kt/Vurea of 2.0 is appropriate, the National Kidney Foundation-Dialysis
      Outcome Quality Initiative Peritoneal Dialysis Adequacy Work Group recommended
      that when the residual renal Kt/Vurea drops below 2.0, supplemental Kt/Vurea
      should be added incrementally by dialysis. This article describes this concept in
      more detail.

PMID- 11443757
TI  - Modality selection.
AB  - Dialysis modality selection should be based on patient preference and medical
      indications. Every effort should be made to provide adequate dosing of dialysis
      by using guidelines supported by clinical outcome evidence. All patients should
      receive explicit information on all modalities of therapy, including
      transplantation, in a balanced presentation before initiation of dialysis. The
      patient should be an active participant in the selection process. The advantages,
      disadvantages, indications, and contraindications for hemodialysis and the
      various modalities of peritoneal dialysis are reviewed in light of the state of
      the art knowledge. Further research is critical to answer three unresolved
      issues: (1) What are the equivalent doses for peritoneal dialysis and
      hemodialysis? (2) Are dialytic and renal clearances equivalent? and (3) Will
      survival improve by providing peritoneal dialysis doses above those currently
      recommended?

PMID- 11443758
TI  - Clinical experience: how much earlier should patients really start renal
      replacement therapy?
AB  - Data are needed to better determine the effect of initiation of dialysis on
      outcome. At present, it is unknown whether any of the previously reported
      improvements in survival "on" dialysis in patients who start "early" is solely
      due to lead time bias. Everyone involved with the care of ESRD patients must
      understand the concept of timely initiation, believe in it, and become fully
      educated about it. Incremental dialysis will require closer follow-up and
      proactive intervention. Protein restriction to prevent progression and timely
      initiation to prevent symptomatology are not mutually exclusive as noted by the
      MDRD experience. It is uncertain how much earlier the average ESRD patient would
      need to start dialysis. However, based on the MDRD experience, timely initiation
      of dialysis may likely only represent starting dialysis 4 to 5 mo sooner than the
      current approach to initiation in patients followed by nephrologists pre-ESRD.
      This "timely" initiation of dialysis would hopefully improve patient outcomes and
      in the long run be less costly. A multicentered, prospective, randomized trial is
      needed to better define the answers to these questions.

PMID- 11443759
TI  - Improving access patency: pre-end-stage renal disease strategies.
AB  - Hemodialysis vascular access has emerged as a major cause of patient morbidity
      and cost in the end-stage renal disease (ESRD) program. It is currently estimated
      that the maintenance and placement of ESRD vascular access may account for up to
      25% of the ESRD budget and the responsible for up to 25% of all hospital stays.
      The National Kidney Foundation Dialysis Outcome Quality Initiative showed that
      arteriovenous (AV) fistulas have a patency and cost that are significantly better
      than native AV grafts. Conversely, new evidence suggests that a rigorous program
      of prospective screening for fibromuscular dysplasia combined with intervention
      significantly improves AV graft longevity to levels approaching AV fistulas but
      at significant cost. Nonetheless, native AV fistulas remain superior, despite
      these advances both in terms of patency and cost. Efforts to increase the number
      of AV fistulas in the prevalent U.S. population are needed. New and innovative
      pre-ESRD strategies that lead to increased percentage of AV fistula formation are
      the goal for rapid improvement in access patency and decrease in access
      morbidity. A primary barrier to native AV fistula formation is lack of timely
      referral. Strategies to increase AV fistula formation require early referral to
      nephrology and early placement of AV fistulas.

PMID- 11443760
TI  - Strategies for optimizing peritoneal dialysis catheter outcomes: catheter
      implantation issues.

PMID- 11443761
TI  - End-stage renal disease patients: referral for transplantation.
AB  - Patients who receive kidney transplants have a higher quality of life, a less
      costly form of therapy, and less risk of death than those who are treated with
      dialysis. This success of transplantation and a simultaneous lack of success in
      increasing the number of cadaveric organ donors has created a supply-demand
      crisis. The United Network of Organ Sharing has attempted to develop a fair
      allocation system for placing patients on waiting lists for kidney
      transplantation. An increase in the number of organs available would allow
      physicians to transplant patients earlier in the time frame of their chronic
      disease.

PMID- 11443762
TI  - Is there data to support the concept that educated, empowered patients have
      better outcomes?
AB  - Achieving positive patient outcomes through the delivery of high quality services
      encompasses a broad range of indicators, including quality of life, employment,
      satisfaction with care, utilization of services, cost-benefit, as well as the
      clinical indices frequently targeted. Empowering and educational initiatives have
      been shown to positively impact the quality of life of renal patients in both the
      psychosocial and functional domains. This has extreme relevance in the context of
      overall care, as empirical evidence has indicated that health-related quality of
      life measures are associated with improved hospitalization and survival. Home
      care and self-care training have been associated with better quality of life
      measures in hemodialysis. Educational efforts have also been associated with
      better outcomes such as decreased utilization of medical services, the
      maintenance of employment, consumer satisfaction with care, and a positive cost
      benefit. There are data to support that the educated, empowered patient has
      better outcomes. This evidence will be explored.

PMID- 11443763
TI  - Epidemiology of cardiovascular disease in chronic renal disease.
AB  - The risk of cardiovascular disease in patients with chronic renal disease appears
      to be far greater than in the general population. For example, among patients
      treated by hemodialysis or peritoneal dialysis, the prevalence of coronary artery
      disease is approximately 40% and the prevalence of left ventricular hypertrophy
      is approximately 75%. Cardiovascular mortality has been estimated to be
      approximately 9% per year. Even after stratification by age, gender, race, and
      the presence or absence of diabetes, cardiovascular mortality in dialysis
      patients is 10 to 20 times higher than in the general population. Patients with
      chronic renal disease should be considered in the highest risk group for
      subsequent cardiovascular events. Cardiac failure is more common in chronic renal
      disease patients than in the general population, and is an independent predictor
      of death in chronic renal disease. Among hemodialysis and peritoneal dialysis
      patients, the prevalence of cardiac failure is approximately 40%. Both coronary
      artery disease and left ventricular hypertrophy are risk factors for the
      development of cardiac failure. In practice, it is difficult to determine whether
      cardiac failure reflects left ventricular dysfunction or extracellular fluid
      volume overload. Patients who develop clinical manifestations of cardiac failure
      should be evaluated for cardiovascular disease.

PMID- 11443764
TI  - Strategies for influencing outcomes in pre-ESRD and ESRD patients.

PMID- 11443765
TI  - Epidemiology of cardiovascular risk factors in chronic renal disease.
AB  - Treatment and prevention of cardiovascular disease in the general population has
      benefited greatly from the identification of cardiovascular disease risk factors.
      Given the particularly high risk of cardiovascular disease and total mortality
      among patients with chronic renal insufficiency (CRI) and end-stage renal disease
      (ESRD), it is important to assess the role of traditional and nontraditional risk
      factors for cardiovascular disease. This review discusses the foundations of risk
      factor epidemiology and briefly summarizes the evidence regarding cardiovascular
      risk factors in renal disease. Diabetes and hypertension have a very high
      prevalence in patients with CRI. Patients with CRI and ESRD also have a higher
      frequency of cardiac dysfunction and left ventricular hypertrophy, which further
      increase the risk of cardiovascular disease. Finally, patients with renal disease
      have a higher prevalence of less established risk factors, including low HDL, and
      high triglycerides, lipoprotein(a), and homocysteine, where prospective studies
      and clinical trials are needed to provide a scientific basis for reduction of
      cardiovascular risk among patients with renal disease.

PMID- 11443766
TI  - Controlling the epidemic of cardiovascular disease in chronic renal disease:
      report from the National Kidney Foundation Task Force on cardiovascular disease.

PMID- 11443767
TI  - Pre-end-stage renal disease care in the United States: a state of disrepair.
AB  - Patients with end-stage renal disease (ESRD) experience significant morbidity and
      mortality. Despite improvements in mortality rates, the life expectancies for
      dialysis patients are still between 16 and 37% of the age-, gender-, and race
      matched U.S. population. One of the factors that thus far has received scant
      attention, but could significantly contribute to morbidity and mortality among
      ESRD patients, is the timing and quality of care before initiation of dialysis
      (pre-ESRD care). Pre-ESRD care involves early detection of progressive renal
      disease, interventions to retard its progression, prevention of uremic
      complications, attenuation of comorbid conditions, adequate preparation for renal
      replacement therapy (RRT), and timely initiation of dialysis. Despite the
      benefits of pre-ESRD care, recent studies suggest that the quality of pre-ESRD
      care in the United States is suboptimal. However, indices of quality of pre-ESRD
      care have been neither clearly defined nor validated. Furthermore, few estimates
      of the size of the pre-ESRD population are available. This review examines the
      prevalence of several factors that could reasonably be used to define suboptimal
      pre-ESRD care, including failure of early detection of renal disease, paucity of
      interventions to slow its progression, predialysis hypoalbuminemia and severe
      anemia, suboptimal pre-ESRD education and uninformed choice of modality of RRT,
      delayed placement of a permanent vascular access, and delayed initiation of RRT.
      Although the data presented strongly suggest that the quality of pre-ESRD care in
      the United States is suboptimal, further research is needed for a better
      definition and validation of indices of quality pre-ESRD care, a more accurate
      estimate of the size of the pre-ESRD population, examination of the causes of
      suboptimal pre-ESRD care, and identification of populations at risk for
      suboptimal pre-ESRD care. This understanding would facilitate development of
      strategies to improve pre-ESRD care and, eventually, outcomes among patients on
      RRT.

PMID- 11443768
TI  - Cardiovascular disease: risk factors, secular trends, and therapeutic guidelines.
AB  - A brief review of cardiovascular disease incidence and risk factors for coronary
      heart disease and cardiac failure is presented. Secular trends in cardiovascular
      disease risk factors, morbidity, and mortality are a major focus. Declines in
      cardiovascular disease mortality over the past 30 yr, a more modest decline in
      coronary heart disease, and an increase in cardiac failure are demonstrated.
      Emphasis is placed on evidence from large-scale, prospective, observational and
      interventional studies, and the pertinent U.S. guidelines and recommendations for
      care are provided. Consideration is given to the major risk factors, including
      lipids, blood pressure, smoking, and diabetes mellitus. Additional information is
      also given concerning the role of vitamins, homocysteine metabolism, and left
      ventricular hypertrophy. Although this review focuses on commonly accepted risk
      factors in the general population, where appropriate, specific information that
      is relevant to patients with chronic renal disease is provided.

PMID- 11443769
TI  - End-stage renal disease treatment: a European perspective.
AB  - There is presently much debate about the optimal flow chart of pre-end-stage
      renal disease (ESRD) and ESRD patients. This article summarizes two important
      nonmedical factors that affect the outcome of ESRD patients in Europe: late
      referral and the structure of the health care system. In a European survey, 30%
      of patients were referred to a nephrologist less than 1 mo before the start of
      renal replacement therapy (RRT). This had an impact on the modality choice, as
      77.5% of late versus 51.1% of early referrals were started on hemodialysis.
      Hospitalization at start of RRT was longer in late versus early referrals (15.1
      +/- 16.0 versus 27.8 +/- 23.7 d respectively, P < 0.001). There were more
      patients without antihypertensive medication in the late referral group (28.6%
      versus 15.5%, P = 0.004), and diastolic BP in this group was higher (83.5 +/-
      15.8 versus 74.4 +/- 15.0 mmHg, P = 0.03). One year after the start of dialysis,
      the number of deaths in the late referrals was higher (26.7 versus 16.4%, P =
      0.07) and the number of transplanted patients was lower (4.7 versus 17.5%, P =
      0.02). Creatinine clearance at start of RRT was 7.0 +/- 3.5 ml/min in the
      patients who died during the first year after start of RRT versus 9.5 +/- 3.6
      ml/min in those surviving. Only 18% of patients were started with a creatinine
      clearance > 10 ml/min, as recommended by the Dialysis Outcomes Quality Initiative
      guidelines. It is concluded that late referral to a nephrologist is still a major
      problem that has a negative influence on modality choice for peritoneal dialysis,
      and on morbidity and mortality of ESRD patients.

PMID- 11443770
TI  - Approach to volume control, cardiac preservation, and blood pressure control in
      the pre-end-stage renal disease patient.

PMID- 11443771
TI  - Angiotensin-converting enzyme inhibitor for slowing progression of diabetic and
      nondiabetic kidney disease.
AB  - A growing body of evidence suggests that agents that inhibit the angiotensin
      converting enzyme are renoprotective. In experimental animal models of chronic
      renal injury, such renoprotection can virtually eliminate progression of the
      renal injury, provided that therapy is started at the time of injury. In humans
      with chronic renal injury, renoprotection has been successfully demonstrated only
      late in the course of the renal disease. The rate of progression to end-stage
      renal failure can be delayed, but progression continues at a slower pace. Further
      study is required to determine whether earlier intervention can better preserve
      nephron structure and function. A strategy for future trials is recommended. It
      emphasizes more sensitive outcome measures so as to achieve greater statistical
      power.

PMID- 11443772
TI  - Prevention of metabolic bone disease in the pre-end-stage renal disease setting.
AB  - The methods for preventing hyperparathyroid bone disease, the major variety of
      renal osteodystrophy, from developing in patients with renal impairment are
      reviewed. With far-advanced chronic renal failure (creatinine clearance [CCr] <
      15 to 20 ml/min), when many of these patients are seen by nephrologists, the use
      of diets very low in protein, and hence also very low in phosphorus content,
      combined with calcium-containing phosphate binders, have been shown to lower
      serum intact PTH levels and improve the osseous pathology. However, the degree of
      dietary restriction required to achieve success may be quite difficult to follow
      by most patients encountered in clinical practice. In less-advanced renal
      insufficiency (CCr, 25 to 60 ml/min), the active vitamin D sterols calcitriol or
      alfacalcidol [1 alpha-hydroxyvitamin D3] have been shown to ameliorate the
      skeletal lesions of renal osteodystrophy. The results of six double-blind,
      placebo-controlled studies and five major open-labeled studies with calcitriol or
      alfacalcidol are reviewed. Skeletal biopsies were improved and sometimes
      normalized by using calcitriol or alfacalcidol in daily doses of 0.25 to 0.5
      microgram/d, and the incidence of hypercalcemia was quite low with these doses.
      When the dosage was increased in one study, there was a higher incidence of
      hypercalcemia. Improved bone mineral density of the spine and hip was reported
      after 1 yr in calcitriol-treated patients compared with results in the placebo
      group. Another report documented more favorable intact PTH suppression with
      intermittent dosing of 2.0 micrograms given either once or three times weekly
      compared with daily dosing (0.5 microgram/d); there was no rise of serum Ca over
      the 3-mo trial with any protcol. Other data support the greater likelihood of
      having normal bone if treatment is initiated when CCr exceeds 25 ml/min. There
      was no risk of more rapid progression of renal insufficiency in any of the
      studies reviewed, which include 242 patients who were given an active vitamin D
      sterol. One trial that used a calcitriol dose of 0.5 microgram/d noted a fall in
      CCr and a rise in serum creatinine, but true GFR (inulin clearance) did not
      change. A calcitriol-induced reduction of tubular creatinine secretion is
      suggested. The risk of inducing low bone turnover (adynamic bone) seems to be
      quite low with 10.4% of alfacalcidol-treated patients versus 6.5% of placebo
      developing this "lesion" after 2 yr. Despite the lack of Food and Drug
      Administration approval for use of these sterols in the predialysis state,
      evidence is compelling that: there are benefits in retarding the development or
      progression of metabolic bone disease; there is minimal risk, providing that low
      doses are used; and there is close monitoring of serum Ca, P, and creatinine. The
      optimal benefits may be obtained if this treatment is started early in the course
      of renal insufficiency (CCr in the range of 25 to 60 ml/min).

PMID- 11443773
TI  - Catabolism in uremia: the impact of metabolic acidosis.
AB  - Chronic metabolic acidosis stimulates the catabolism of bone and muscle in
      experimental animals and humans. The toxicity caused by acidosis involves changes
      in endocrine function and toxicity arising from the homeostatic responses that
      are activated by the body to maintain pH near normal levels. Glucocorticoids,
      insulin, insulin-like growth factor-1, and parathyroid hormone play important
      roles in the homeostatic responses of bone and muscle to acid. Bone buffering of
      acid and the resulting increase in renal calcium excretion leads to negative
      calcium balance. Activation of the ubiquitin-proteasome proteolytic system and
      branched-chain ketoacid dehydrogenase in muscle, along with hepatic glutamine
      synthesis in the liver and renal glutamine uptake, are homeostatic mechanisms
      that cause negative nitrogen balance and loss of muscle mass. Treating the
      acidosis of chronic renal insufficiency improves both bone and muscle metabolism
      by reducing the loss of calcium and protein and amino acids in the two organs,
      respectively. Thus, treating acidosis suppresses both bone and muscle catabolism
      in patients with normal and reduced renal function.

PMID- 11443774
TI  - Anemia in predialysis chronic renal failure: what are we treating?

PMID- 11443775
TI  - Growth retardation in children with chronic renal insufficiency.
AB  - Progressive growth retardation is a complication of chronic renal insufficiency
      (CRI) in children and often results in patients attaining a final adult height SD
      score of -1.88 or worse. Although a host of factors may contribute to the
      subnormal height velocity associated with CRI, disorders of the growth
      hormone/insulin-like growth factor (IGF) axis predominate. An excess of one or
      more of the six IGF binding proteins in the 35-kD serum fractions results in
      depressed bioactivity of the IGF and impaired stimulation of linear growth.
      Treatment with recombinant human growth hormone likely increases the IGF levels
      in the 35-kD serum fractions and restores IGF bioactivity, which is associated
      with an increase in height velocity. Nevertheless, the use of recombinant human
      growth hormone remains limited in patients with CRI, and more than one-third of
      this population are severely growth-retarded. Strategies designed to
      prevent/correct the growth retardation that accompanies CRI should ideally occur
      during the pre-end-stage renal disease period.

PMID- 11443776
TI  - The role of the nephrologist in ESRD/Pre-ESRD care: a collaborative approach.
AB  - The number of patients with chronic renal failure and end-stage renal disease
      continues to increase. Nonetheless, there are increasing pressures to decrease
      the number of nephrologists. To provide highly specialized care for these complex
      patients, nephrologists must render less care for more patients, or allow less
      qualified providers to render care. Use of a highly specialized professional
      colleague, the properly trained nephrology nurse practitioner, allows the
      nephrologist to provide care for a great number of patients while maintaining
      quality using an integrated collaborative practice model. This article describes
      the successful use of nurse practitioners to extend the scope of nephrology care
      with this paradigm. This model allows the nephrologist to provide specialized
      care to more patients, maintain quality control, improve cost effectiveness of
      care rendered, and is enthusiastically embraced by the patients cared for by the
      team.

PMID- 11443777
TI  - Argument for timely initiation of dialysis.

PMID- 11443778
TI  - Environmental concerns move to the forefront: an interview with DEP Deputy
      Secretary Robert Barkanic. Interview by Dr. Richard Galeone.

PMID- 11443779
TI  - Environmental Task Force update.

PMID- 11443780
TI  - Household hazardous waste: what can you do about it?

PMID- 11443781
TI  - First, do no harm.

PMID- 11443782
TI  - Let wisdom & experience guide you.

PMID- 11443783
TI  - Getting off to the right start in your new practice.
AB  - Purchasing and starting up a new practice is one of the most important moves you
      will make in your career. Anticipating and responding effectively to day-to-day
      situations can help get you off to the right start in building the kind of
      practice you've always wanted.

PMID- 11443784
TI  - Is a partnership or associateship right for you?
AB  - Weight your options carefully before bringing another dentist into your practice.
      This includes careful evaluation of your current situation and what you hope to
      achieve in the future.

PMID- 11443785
TI  - Contracting with third-party payors. A primer for the new practitioner.
AB  - The options for billing and receiving dental fees have increased in recent years.
      The savvy dentist will make sure he or she understands all the options before
      signing on to a particular plan.

PMID- 11443786
TI  - Dental design basics.
AB  - For some dentists, designing their office was the most rewarding phase of
      establishing their practice. Providing services in an environment that enables
      and enhances quality, with a staff that enjoys coming to work, is professionally
      fulfilling. Take your time, consult with respected professionals and insist on
      the best.

PMID- 11443787
TI  - If you don't have something good to say, stick with the facts.

PMID- 11443788
TI  - Third-party blues.

PMID- 11443789
TI  - Effect of pulsed Nd:YAG laser irradiation on acid demineralization of enamel and
      dentin.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of Nd:YAG
      laser irradiation on the acid demineralization of enamel and dentin by
      spectrophotometry. A mechanism of acquired acid resistance is also proposed.
      SUMMARY BACKGROUND DATA: The ability of Nd:YAG laser irradiation to the enhanced
      resistance to artificial caries formation is still controversial. METHODS: A
      pulsed Nd:YAG laser at 1.064-micron wavelength was used to irradiate the human
      enamel and dentin samples from 20 extracted human molars at the parameters of 1,
      2, and 3 W and 20 pps for a total of 9 sec after painting with black ink. Samples
      were then subjected to 2 microliters of 0.1 M lactic acid solution (pH 4.8) for
      24 h at 36 degrees C. The parts per million (ppm) of calcium ion (Ca2+) dissolved
      in each solution was determined by atomic absorption spectrophotometry and the
      morphological changes were also investigated by scanning electron microscopy
      (SEM). RESULTS: The lowest mean Ca2+ ppm was recorded in the samples irradiated
      at 3 W, in those by irradiated at 2 W and 1 W. The unlased samples showed the
      highest Ca2+ ppm. SEM observation showed that in the lased areas, the smear layer
      was partially melted and the underlying primary enamel or dentin seemed to be
      thermally degenerated. CONCLUSIONS: The results of this study suggested that
      melted smear layer and underlying enamel or dentin degenerated thermally by the
      heat treatment of Nd:YAG laser might play a major role to enhance resistance to
      artificial caries-like formation.

PMID- 11443790
TI  - Light, enlightenment, and learning.

PMID- 11443791
TI  - Modulator of heme biosynthesis induces apoptosis in leukemia cells.
AB  - OBJECTIVE: The purpose of this research is the investigation of the possible
      cause(s) of the dark-cell death phenomenon induced by 1,10-phenanthroline (Oph),
      a porphyrin biosynthesis modulator. SUMMARY BACKGROUND DATA: We have previously
      shown that porphyrin biosynthesis modulators, such as Oph, which is also an iron
      chelating agent, enhance protoporphyrin IX (Proto) accumulation in mammalian
      neoplastic cells treated with delta-aminolevulinic acid (ALA). As a result of the
      enhanced Proto accumulation, a significant increase in photodynamic damage was
      observed under illumination. Also tetrapyrrole and heme-biosynthesis modulators
      have been shown to cause death in treated insect larvae in darkness, a phenomenon
      referred to as dark-cell death. Dark-cell death was also observed in Oph + ALA
      treated transformed mammalian cells. METHODS: Neoplastic cells were treated with
      ALA, Oph, and ALA + Oph, and the following cell properties were investigated:
      growth arrest, membrane permeability, cell survival, nucleosomal cleavage, and
      cell cycle alterations. RESULTS: It was observed that Oph but not ALA induced
      growth arrest, in a T-cell leukemia line (MLA 144) as assessed by reduction in
      DNA synthesis. Exogenous Proto and isomers of Oph lacking the iron-chelating
      property of Oph also caused a dose-dependent inhibition of proliferation in MLA
      144 cells. Although the plasma membrane of Oph-treated cells remained intact
      following 3 h of dark-incubation, the cells exhibited DNA internucleosomal
      cleavage, characteristic of cells undergoing apoptosis. Cell cycle analysis using
      the DNA intercalating dye propidium iodide (PI) coupled to flow cytometry,
      indicated that 81 +/- 5.6% of Oph-treated MLA 144 cells were apoptotic, with the
      majority of the cells arrested in the early S phase. On the other hand, treatment
      with either ALA or Proto did not alter the cell cycle. Also, using a double
      labeling protocol with Hoechst 33342, and PI, and analysis by flow cytometry, Oph
      treated cells were found to be 82% apoptotic after 3 h of dark-incubation.
      Apoptosis was reduced by 75% (p < 0.05) by the cytoplasmic protein synthesis
      inhibitor cycloheximide. CONCLUSIONS: These results indicate that in addition to
      enhancing Proto accumulation, the heme biosynthesis modulator Oph also induces
      growth arrest and apoptosis in transformed cells in darkness.

PMID- 11443792
TI  - Effects of erbium, chromium:YSGG laser irradiation on root surface: morphological
      and atomic analytical studies.
AB  - OBJECTIVE: The purpose of this study was to investigate the morphological and
      atomic changes on the root surface by stereoscopy, field emission-scanning
      electron microscopy (FE-SEM), and energy dispersive X-ray spectroscopy (SEM-EDX)
      after erbium, chromium:yttrium, scandium, gallium, garnet (Er,Cr:YSGG) laser
      irradiation in vitro. SUMMARY BACKGROUND DATA: There have been few reports on
      morphological and atomic analytical study on root surface by Er,Cr:YSGG laser
      irradiation. METHODS: Eighteen extracted human premolar and molar teeth were
      irradiated on root surfaces at a vertical position with water-air spray by an
      Er,Cr:YSGG laser at the parameter of 5.0 W and 20 Hz for 5 sec while moving. The
      samples were then morphologically observed by stereoscopy and FE-SEM and examined
      atomic-analytically by SEM-EDX. RESULTS: Craters having rough but clean surfaces
      and no melting or carbonization were observed in the samples. An atomic
      analytical examination showed that the calcium ratio to phosphorus showed no
      significant changes between the control and irradiated areas (p > 0.01).
      CONCLUSIONS: These results showed that the Er,Cr:YSGG laser has a good cutting
      effect on root surface and causes no burning or melting after laser irradiation.

PMID- 11443793
TI  - Endoscopic foraminoplasty: a prospective study on 250 consecutive patients with
      independent evaluation.
AB  - OBJECTIVE: This study focused on the efficacy of endoscopic decompression of the
      foramen guided by endoscopic aware-state pain source definition. BACKGROUND DATA:
      Endoscopic foraminoplasty consists of undercutting of the facet joint and
      endoscopic discectomy, mobilization and neurolysis of the exiting and transiting
      nerves, and ablation of osteophytes. This study sought the outcome of endoscopic
      foraminoplasty in 250 consecutive patients followed for a minimum of 2 years,
      reviewed and assessed by an external independent assessor. It was applied to
      patients with back pain and sciatica in multilevel degenerative disc disease and
      also to those with prior surgery. METHODS: A prospective study of endoscopic
      laser foraminoplasty was performed on 121 males and 129 females with an average
      age of 48 years (21-86 years), followed for an average period of 30 months (26-43
      months). The average preoperative duration of back, buttock, or leg pain was 6.1
      years (5-11 years). A total of 30% had undergone prior open spinal surgery.
      RESULTS: The cohort integrity at follow up was 97%. Outcome was analyzed using
      the percentage change in Oswestry Disability Scores and visual analogue pain
      scores. Clinically relevant change in pain and disability was observed in 73%.
      Using a percentage change in Oswestry Disability Score of 50 or more to determine
      good and excellent outcomes, 60% of patients exceeded this score. A total of 95%
      patients required no further surgical intervention. CONCLUSIONS: Endoscopic laser
      foraminoplasty provides a minimalist means of exploring the extraforaminal zone,
      the foramen, the disc, and the epidural space and performing discectomy, lateral
      recess decompression, osteophytectomy, and neural mobilization. Performed in the
      aware state, it serves to identify and localize precisely the causal source of
      pain in multilevel disc disease, in revision surgery, and in the infirm and
      elderly without open fusion or decompression.

PMID- 11443794
TI  - Microleakage of a resin sealant after acid-etching, Er:YAG laser irradiation and
      air-abrasion of pits and fissures.
AB  - OBJECTIVE: The aim of this in vitro study was to assess microleakage underneath a
      filled pit-and-fissure sealant bonded to occlusal surfaces treated by four enamel
      etching techniques. SUMMARY BACKGROUND DATA: There has been no report of a study
      assessing microleakage of a pit-and-fissure sealant, comparing acid-etching,
      Er:YAG laser and air-abrasion for treating enamel surface. METHODS: Forty
      extracted human third molars were selected and randomly assigned into four groups
      of ten teeth: group I, the occlusal surfaces were acid-etched; group II, a very
      short pulsed Er:YAG laser was used to treat the surfaces; group III, aluminum
      oxide air-abrasion was associated with acid-etching; group IV, Er:YAG laser was
      associated with acid-conditioning. The surfaces were sealed and the teeth were
      stored for 7 days in distilled water. Then, specimens were thermocycled, immersed
      in a 0.2% rhodamine solution, sectioned, and analyzed for leakage using an
      optical microscope connected to a video camera. The images were digitized and
      analyzed by software that allowed microleakage assessment in millimeters.
      RESULTS: Statistical analysis showed that occlusal surfaces treated exclusively
      by the Er:YAG laser (group II) provided the poorest marginal sealing and that
      acid-etching (group I) was statistically similar to aluminum oxide air-abrasion +
      acid etching (group III) and to Er:YAG laser + acid-etching (group IV).
      CONCLUSIONS: The results suggest that complementing either air-abrasion or Er:YAG
      laser irradiation with a subsequent acid-conditioning did not lessen microleakage
      at the enamel-sealant interface when compared with an acid-etched group. It was
      also observed that treating the enamel surface exclusively by Er:YAG laser
      resulted in the highest degree of leakage.

PMID- 11443795
TI  - Relative variation to received dose of some erythrocytic and leukocytic indices
      of human blood as a result of low-level laser radiation: an in vitro study.
AB  - OBJECTIVE: This study investigated the in vitro effects of low-level laser
      radiation (LLLR) on selected rheologic constants of the human blood. The
      variations of CBC parameters to the received dose were determined, as well as of
      blood viscosity (an erythrocyte aggregation index), as a research method for some
      structural alteration of blood proteins. This was also confirmed by the
      electrophoretic study of plasma proteins from the irradiated blood. METHODS:
      Fresh blood samples (whole blood) from 16 adult regular blood donors were
      irradiated with a He-Ne laser (lambda = 632.8 nm; power output = 6 mW; mean
      irradiance on blood samples approximately 180 mW.cm-2; beam spot diameter
      approximately 2 mm), operating in continuous wave. Doses ranged between 0
      (control sample) and 9.346 J.cm-3.EDTA (for CBC and viscosity measurements) or
      citrate (for electrophoresis) anticoagulant was used. Measurements were performed
      before (control samples) and after irradiation. In most of the cases, the
      measurements were made immediately after irradiation. In some cases, the
      measurements were made after 24 or 48 h after irradiation, respectively, to
      conclude whether the modifications caused from irradiation occur in time, or
      immediately after irradiation. RESULTS: Following irradiation, marked variations
      of some erythrocyte and leukocyte indices and changes of the erythrocyte
      aggregation (viscosity), as a function of received dose, were observed.
      Significant differences between control and irradiated blood samples were found
      for the following rheologic factors: RBC (in 22.2% of cases); HGB (26.8%); HCT
      (82.4%); MONO and GRAN (36.7%); viscosity (82.5%). From the plasma proteins:
      albumin (22.2%); alpha 1 globulin and gamma globulin (18.5%); fibrinogen (70.4%).
      In most of the cases, remarkable effects (maxima) were noticed around 1.2 J.cm-3
      dose value. We consider this dose value as optimal, one that can lead to
      beneficial effects. The cell membrane integrity was not affected from
      irradiation, for doses between 0 and 9.346 J.cm-3, and will probably not even be
      affected at higher doses (see MCV and MCHC behavior). CONCLUSIONS: The effect of
      LLLR on red blood cells confirms the nonresonant mechanism of this biostimulating
      effect, by the changes occurring in the cell membrane (in our case, blood cells),
      by revitalizing of red blood cell functional capacities and by several
      biochemical effects at the membrane's level. These are to be studied thoroughly
      in future studies. The physical-biochemical and biological effects caused by LLLR
      on blood can influence the physical-chemical parameters needed for the long-term
      storage of blood products. These effects can also lead to a quicker
      revitalization of the erythrocyte membrane (which was subjected to the action of
      some physical and biochemical factors during the preservation process), to
      perform its oxyphoric function in transfusion procedures.

PMID- 11443796
TI  - Cosmetic makeover simulations in a windows environment, Part 2: Marketing tool
      strategies.

PMID- 11443797
TI  - Digital radiography: tips for clinical practice.

PMID- 11443798
TI  - Transform your practice with high technique, Part 1: How technology solves
      staffing problems.

PMID- 11443799
TI  - Watch your head (overhead, that is).

PMID- 11443800
TI  - Brave new mouth?

PMID- 11443801
TI  - NIH examines current state of caries research.

PMID- 11443802
TI  - World TB day highlights global concern for deadly disease.

PMID- 11443803
TI  - Surgical errors are the most frequent, most costly.

PMID- 11443804
TI  - New PDR for Nutritional Supplements evaluates validity of health claims.

PMID- 11443805
TI  - Chlorhexidine: a periodontal alternative.

PMID- 11443806
TI  - The link between chronic smoking and periodontal disease.

PMID- 11443807
TI  - Women have special oral health needs.

PMID- 11443808
TI  - Smile aesthetics demands teamwork.

PMID- 11443809
TI  - Survey focuses on powered toothbrushes.

PMID- 11443810
TI  - Productive hygiene scheduling: is anyone in charge?

PMID- 11443811
TI  - Introduction of a new rotary endodontic system: progressively tapering files.

PMID- 11443812
TI  - Canal diameter: the forgotten dimension.

PMID- 11443813
TI  - Common sense dentistry.

PMID- 11443814
TI  - Herpes simplex virus: clinical presentation and treatment.

PMID- 11443815
TI  - Improve your bleaching results with bleaching trays that fit.

PMID- 11443816
TI  - Ultimate provisionals.

PMID- 11443817
TI  - Veneer preparations using a clear stint reduction guide.

PMID- 11443818
TI  - Sharing techniques.

PMID- 11443819
TI  - Occlusion problems.

PMID- 11443820
TI  - Laser vs laser.

PMID- 11443821
TI  - The art of the reline.

PMID- 11443822
TI  - Winning the mind of the patient, Part 3: How a new caries classification system
      causes "little hinges to swing big doors" in patient perception.

PMID- 11443823
TI  - Oral cancer: the role of the dentist in prevention and early detection.

PMID- 11443824
TI  - Combining microabrasion with tooth whitening to treat enamel defects.

PMID- 11443825
TI  - Craniofacial muscle pain: review of mechanisms and clinical manifestations.
AB  - Epidemiologic surveys of temporomandibular disorders (TMD) have demonstrated that
      a considerable proportion of the population--up to 5% or 6%--will experience
      persistent pain severe enough to seek treatment. Unfortunately, the current
      diagnostic classification of craniofacial muscle pain is based on descriptions of
      signs and symptoms rather than on knowledge of pain mechanisms. Furthermore, the
      pathophysiology and etiology of craniofacial muscle pain are not known in
      sufficient detail to allow causal treatment. Many hypotheses have been proposed
      to explain cause-effect relationships; however, it is still uncertain what may be
      the cause of muscle pain and what is the effect of muscle pain. This article
      reviews the literature in which craniofacial muscle pain has been induced by
      experimental techniques in animals and human volunteers and in which the effects
      on somatosensory and motor function have been assessed under standardized
      conditions. This information is compared to the clinical correlates, which can be
      derived from the numerous cross-sectional studies in patients with craniofacial
      muscle pain. The experimental literature clearly indicates that muscle pain has
      significant effects on both somatosensory and craniofacial motor function.
      Typical somatosensory manifestations of experimental muscle pain are referred
      pain and increased sensitivity of homotopic areas. The craniofacial motor
      function is inhibited mainly during experimental muscle pain, but phase-dependent
      excitation is also found during mastication to reduce the amplitude and velocity
      of jaw movements. The underlying neurobiologic mechanisms probably involve
      varying combinations of sensitization of peripheral afferents, hyperexcitability
      of central neurons, and imbalance in descending pain modulatory systems. Reflex
      circuits in the brain stem seem important for the adjustment of sensorimotor
      function in the presence of craniofacial pain. Changes in somatosensory and motor
      function may therefore be viewed as consequences of pain and not factors leading
      to pain. Implications for the diagnosis and management of persistent muscle pain
      are discussed from this perspective.

PMID- 11443826
TI  - Aural symptoms in temporomandibular disorder patients attending a craniofacial
      pain unit.
AB  - AIMS: To determine (1) the prevalence of aural symptoms in orofacial pain
      patients and (2) a potential association between temporomandibular disorders
      (TMD) and aural health, while controlling for covariates known to be associated
      with TMD or auditory dysfunction. METHODS: In a retrospective study, health
      questionnaires, medical histories, clinical findings, diagnoses, and treatments
      were systematically retrieved from the charts of 776 patients. The dates of
      initial assessment ranged from May 1987 to June 1999. Of the included subjects,
      39.7% were female; the median age was 39 years; 16.4% displayed only aural
      symptoms (otalgia, tinnitus, vertigo, or perceived hearing loss); 26.4% had both
      TMD and aural symptoms; 17.8% had TMD but no aural complaints; and 39.4% had
      neither TMD nor aural symptoms. RESULTS: Of the 344 subjects who had TMD, 59.9%
      complained of aural symptoms, versus 29.2% of the 432 patients without TMD. Of
      the subjects with otalgia, tinnitus, vertigo, or perceived hearing loss, 67%,
      64.1%, 65.2%, and 62.2% had TMD, respectively. Subjects with aural symptoms were
      significantly more likely to be female; to consider themselves in poor health; to
      smoke; or to have TMD, orofacial pain, headaches (temporal, occipital, or
      frontal), neck and shoulder pain, altered vision and sensation, sleep
      disturbances, loss of appetite, memory loss, or low energy. Clinical findings
      indicated that pathognomonic signs of TMD were associated with an increased risk
      of aural complaints in this patient population. A significantly greater negative
      impact on normal life functions was found in subjects exhibiting aural symptoms
      versus those who only had TMD complaints. CONCLUSION: These findings indicate
      that TMD is significantly correlated to aural health, although no cause-and
      effect relationship has yet been demonstrated. Aural symptoms were also found to
      have a measurable impact on the subjects' quality of life.

PMID- 11443827
TI  - Health care utilization and cost among health maintenance organization members
      with temporomandibular disorders.
AB  - AIMS: Little has been reported on the use of health care services and consequent
      costs among persons with temporomandibular disorders (TMD). This project compared
      the use and cost of medical and dental care services for TMD patients and matched
      comparison subjects. METHODS: Patients were continuously enrolled members of
      Kaiser Permanente Northwest Division who had at least 1 TMD Clinic visit or TMD
      related procedure between January 1990 and December 1995 (n = 8,801). An equal
      number of comparison subjects were identified electronically and matched on 14
      variables, including age and gender. Utilization and cost estimates were
      determined and compared for selected medical and dental services. RESULTS: For
      both groups, the mean age was about 40.5 years, and approximately 80% were
      female. The TMD subjects used significantly more services than did comparison
      subjects and had mean costs that were 1.6 times higher for all services.
      Outpatient visits accounted for about 40% of the difference in mean costs. About
      10% of TMD subjects and comparison subjects accounted for about 40% and 47% of
      the costs in each group, respectively. Female TMD subjects and comparison
      subjects had higher costs than their male counterparts, and male TMD subjects had
      higher costs than female comparison subjects. CONCLUSION: Patients with TMD used
      more of all types of services and had higher costs. A small proportion of the
      subjects accounted for a large proportion of the costs. Gender was an important
      factor in utilization and cost. Utilization and cost differences were consistent
      over a wide range of service categories and could not be explained by TMD alone.

PMID- 11443829
TI  - The promises and pitfalls of polymorphisms and pain.

PMID- 11443828
TI  - Orofacial pain as the sole manifestation of syringobulbia-syringomyelia
      associated with Arnold-Chiari malformation.
AB  - This is a case report of a male patient who presented with orofacial pain for a
      year as the only manifestation of syringobulbia-syringomyelia associated with
      Arnold-Chiari malformation. This article places emphasis on the clinical
      presentation and possible differential diagnoses. The pain was continuous and
      affected the left side of the face. It was exacerbated by coughing and physical
      effort, possibly as a consequence of an increase in intracranial pressure.
      Paroxysmal pain crises developed over this background of continuous pain,
      compatible with neurogenic trigeminal pain of the left second branch, together
      with pain episodes similar to cluster headache on the same side. The symptoms
      were resolved following neurosurgical management with amplification of the
      foramen magnum.

PMID- 11443830
TI  - The etiology of temporomandibular disorders: implications for treatment.
AB  - This article begins by reviewing the history of etiologic thinking in the field
      of temporomandibular disorders (TMD). I conclude from this review that not only
      are the old mechanistic etiologic concepts incorrect, but also that 2 of the most
      popular current concepts (biopsychosocial and multifactorial) are seriously
      flawed. Therefore, what we really have at the individual TMD patient level is
      nearly always an idiopathic situation--we simply do not know enough, or cannot
      measure enough, or cannot precisely determine why each patient has a TMD. In
      addition, we do not understand the host resistance factors that ultimately
      determine why one person gets sick while another does not. The issue of "why"
      (etiology) must be differentiated from the issue of "how" (pathophysiology), both
      semantically and intellectually, to discuss all of this properly. However, our
      current inability to precisely identify etiologies in TMD patients does not
      prevent us from providing sensible (and often successful) treatment for most of
      these patients. Many health conditions currently are treated by physicians and
      dentists with either incomplete or flawed understanding of their etiology, but
      the availability of empirical data about treatment outcomes permits some level of
      appropriate care to be given. Fortunately, a large number of comparative studies
      have been done in the field of TMD therapy, providing us with a basis for
      selecting initial therapies as well as for dealing with treatment failures. Even
      in the absence of a perfect understanding of etiology, we still can provide good
      conservative care, and we should avoid aggressive and irreversible treatments,
      especially when they are based on flawed concepts of etiology. The article
      concludes by discussing current basic science research activities in the field of
      TMD and orofacial pain. I propose that these ongoing studies of the molecular and
      cellular mechanisms of joint disease, muscle pain, and chronic pain are the most
      likely avenues to future progress in this field, as specific countermeasures are
      developed to become the basis for more precisely targeted therapies.

PMID- 11443831
TI  - [Balance nutrition in the diabetic patient].
AB  - Nutrition is an integral part of the monitoring and care of diabetes. Compliance
      with a nutritional plan is, however, one of the most difficult goals to achieve
      due to the changes in lifestyle that it implies. In order to integrate nutrition
      effectively into the follow-up and control of diabetic patients, it is necessary
      to have a multidisciplinary team of professionals basically comprising a doctor
      specializing in Endocrinology and Nutrition, a dietician and a trainer in
      diabetes issues. These team members have to apply an individualized approach for
      each patient and provide nutritional education to enable patients to be self
      sufficient. Test results (blood-glucose levels, HbA1c, lipids, blood pressure and
      quality of life) must be regularly assessed and, if the desired goals are not
      achieved, the necessary changes must be indicated for future monitoring and
      overall management of the condition.

PMID- 11443832
TI  - [Relation between the viscosity of enteral diets and mechanical complications in
      their administration according to the nasogastric catheters].
AB  - OBJECTIVE: The use of enteral nutrition has increased enormously over the last
      few years and at the same time the standard indications for parenteral nutrition,
      whether in hospitals or at home, have gradually been defined. The most common way
      to administer enteral nutrition is intermittently and using gravity, through a
      nasogastric catheter or through gastrostomy. In our daily practice it has been
      observed that there was at times a considerable delay in the administration of
      the diet by means of a nasogastric catheter and the tube was sometimes blocked
      due to its small calibre and/or the excessive viscosity of the formula. It was
      therefore proposed to study the viscosities of polymeric enteral diets with and
      without fibre at this hospital to identify the relationship with the time taken
      for their intermittent, gravity-driven administration through different calibres
      of nasogastric catheter at the maximum flow rate. RESULTS: Some of the enteral
      diets under study exceeded the recommended time for intermittent administration
      by gravity (20-40 minutes). CONCLUSIONS: We feel it is essential for the product
      label to provide information on the optimal calibre of the nasogastric catheter
      required for administration of the product.

PMID- 11443833
TI  - [Audit of artificial nutrition in an intensive care unit].
AB  - OBJECTIVE: To study compliance with an artificial nutrition protocol at an
      Intensive Care Unit. During a second stage and after introducing the
      modifications considered appropriate in the protocol, to verify its
      implementation and compare both series. REFERENCE POPULATION: All patients with
      artificial nutrition support were included. Artificial nutrition (AN) was deemed
      to be the dispensation of commercial preparations for enteral nutrition, formulas
      with amino acids and glucose and the parenteral provision of fat, including
      propofol in this case, even where it was the only source of energy. The provision
      of crystalloid solutions was not considered to be AN. The period of observation
      was two months in both cases. INTERVENTION: The provision of AN to all such
      patients was systematically recorded on a daily basis. After analysis of the
      first series, the members at the unit agreed to increase the nitrogen provision.
      A second series was recorded, with the data being collected for patients with AN
      during a similar period. RESULTS: The study of the first series revealed the
      provisions of energy and nitrogen were below theoretical levels (both in the
      corrected Harris-Benedict test and at the fixed prescription of 25 kcal/kg). In
      the second series, there was greater agreement between the theoretical values and
      the amounts actually received. The deviation in energy and nitrogen was
      significantly less in the second series. And although the total nitrogen load per
      patient did not reveal any differences, there were discrepancies in the daily
      provision per patient. On most days, the diet provided covered over 75% of the
      energy requirements. With parenteral nutrition on its own or in combination with
      enteral nutrition, the requirements of energy and nitrogen were exceeded. There
      were no differences between the two series. The type of provision was enteral on
      55% of the days and parenteral on 18%. There was no difference in the type of
      provision between the two series, although there was a difference in the type of
      diet administered in that the second series saw a significant increase in the
      provision of hyperproteic diets, both enterally and through patenteral
      formulations, rising from 9-13 grammes to 18-20 grammes of nitrogen. Using the
      enteral route on its own, there was a discreet increase in the energy load in the
      second series, but this did not occur in the other types of provision. Both
      series revealed over-nutrition in terms of both calories and nitrogen when
      enteral and parenteral nutrition were used together, although there was no
      difference between the series. CONCLUSIONS: Early enteral nutrition is possible
      in critically-ill patients, while artificial nutrition was used most frequently
      and for longer in our patients. The existence of nutrition protocols allow
      acceptable levels of nutritional provision. Their controlled use allows the
      correction of deviations between real and theoretical provisions, customizing the
      nutrition for each patient. The use of parenteral formulas with high levels of
      nitrogen requires more accurate adjustment in order to avoid over-nutrition.

PMID- 11443834
TI  - [Evaluation of a dessert in patients with deglutition changes, one more step in
      advanced basic feeding].
AB  - BACKGROUND: Decrease in the capacity to deglutition solids and liquids is a
      problem in many people, this problem decreases quality of life. The objective of
      our work is to evaluate the acceptance degree of a dessert (stewed fruit)
      (including in the normal diet of the Hospital) in a group of patients with
      dysphagia. METHODS: Forty seven patients were studied in Hospital Universitario
      del Rio Hortega (Valladolid) in July of 2000. The main pathology of these
      patients was; (n = 12) 25.5% acute stroke, (n = 16) 34% aerodigestive tumors
      (Jarynx carcinoma (n = 5), cavum carcinoma (n = 9), oesophagus carcinoma (n = 2))
      and 40.4% (n = 19) chronic neurologic disease (Alzheimer, vascular dementia, and
      parkinson). All patients took a oral triturated diet, a dessert with apple and
      pear (Resource fruits Instant). All patients took a portion of the dessert and
      after that a acceptance questionnaire was filled. RESULTS: Global acceptance of
      the product was 7.25 +/- 1.5, this punctuation was higher in the tumoral group 8
      +/- 1.1 points, 6.86 +/- 1.4 in patients with acute stroke and 6.7 +/- 1.5 in
      patients with chronic neurologic disease (p < 0.05). Different organoleptic
      characteristics were analyzed, mean punctuation in texture was 1.79 +/- 0.6,
      color 2.2 +/- 0.5, smell 2.24 +/- 0.59 and taste 1.95 +/- 0.61, in a scale of 1
      (very good) until 5 (very bad), a total of 57.9% patients responded very good (1)
      or good (2) in texture scale, 71.1% in color scale, 60.5% in smell scale and
      63.2% in taste scale. CONCLUSIONS: Acceptance of this product in patients with
      dysphagia has been elevated, showing useful in these patients with nutrition
      alterations.

PMID- 11443835
TI  - Risk factors for malnutrition in patients undergoing gastroenterological and
      hernia surgery: an analysis of 374 patients.
AB  - OBJECTIVE: The aim of this study was to assess the nutritional status of 374
      surgical patients with gastrointestinal disease and hernias of the abdominal
      wall; to identify risk factors associated with a poorer nutritional status in
      this group of patients and to assess awareness of the patient's nutritional
      status by medical teams. SUMMARY BACKGROUND DATA: Malnutrition is prevalent among
      surgical patients and is associated with higher surgical complication rates and
      mortality. The major causes of poor nutritional status are related to the
      underlying disease, socio-economic factors, age, and length of hospitalization.
      Despite its high prevalence, medical teams often overlook malnutrition, and
      screening of these patients is not routine. It is of utmost importance to
      identify patients at risk for malnutrition in order to prevent related
      complications. METHODS: The 374 patients evaluated in this study were a subgroup
      of a larger multicenter, cross-sectional, randomized study that was carried out
      in 1996. Nutritional status was assessed by using Subjective Global Assessment.
      RESULTS: Malnutrition was present in 55% of the patients, with 19% of the
      patients severely malnourished. The presence of cancer, infection, age over 60
      years, upper gastrointestinal disease, and longer length of hospital stay all
      negatively influenced nutritional status. Despite the high prevalence of
      malnutrition, the medical teams only assessed the nutritional status of a few
      patients. CONCLUSION: Malnutrition was highly prevalent in this setting of
      patients. Therefore, patients with the risk factors above presented should
      routinely undergo nutritional screening and/or assessment in order to be able to
      early diagnose or prevent malnutrition and its correlated morbidity and
      mortality.

PMID- 11443836
TI  - Clusters of Shigella sonnei in men who have sex with men, British Columbia, 2001.

PMID- 11443837
TI  - Fatal and severe hepatitis associated with rifampin and pyrazinamide for the
      treatment of latent tuberculosis infection--New York and Georgia, 2000.

PMID- 11443838
TI  - [Endovascular treatment of abdominal aorta aneurysm in high risk patients].

PMID- 11443839
TI  - [Genetics-based prognosis evaluation of patients surgically treated for sporadic
      colorectal cancer].
AB  - The basic assumption as rationale of this research was that DNA repair genes (MMR
      system) are at beginning of the genetic mutational cascade causing the induction
      of oncogenesis of sporadic colorectal cancers as well as their multiclonal
      heterogeneity. In a previous study the Authors randomly selected, from a series
      of 256 patients, 29 patients up to the age of 60 years who underwent surgery for
      colorectal carcinoma with radical intent. All selected cases were considered as
      sporadic cancers from a clinical point of view, since none of them fulfilled the
      Amsterdam criteria for HNPCC and familial adenomatous polyposis was included too.
      Mismatch repair gene proteins expression and, in particular, gene hMSH2 protein
      was investigated by immunohistochemistry analysis. In 12 cases (41.4%) hMSH2
      exhibited strong expression in the tumoral cells as well as in the surrounding
      mucosa and at distant mucosa. In 14 cases (48.3%) loss of hMSH2 protein
      expression was observed in tumoral cells and low immunoreactivity was detected in
      peritumoral mucosa while strong hMSH2 expression was observed in distant mucosa.
      In a third small group of patients (10.3%) loss of hMSH2 protein expression was
      detected in tumoral, adjacent and at distance normal mucosa. After a five years
      follow up, 100% of twelve patients of first group are still alive vs 64.3% of
      fourteen patients of second group, while in the third group only one patient
      survives. These results support the hypothesis of an involvement of hMSH2 gene
      defect in development of a subset of sporadic colorectal cancer. For the patients
      with strong expression of hMSH2 in the tumoral cells as well as in the
      surrounding mucosa and at distant mucosa, this parameter could represent an
      independent criterion for a good prognostic value.

PMID- 11443840
TI  - Breast cancer in pregnancy.
AB  - Breast cancer in pregnancy involves a psychosocial, religious, multidisciplinary
      medical decision. From 1991 the Authors have surgically treated six patients
      affected by breast cancer in pregnancy. The Authors, in this papers, review
      analysing current therapeutic approach for this disease.

PMID- 11443841
TI  - [Non-parasitic splenic cysts].
AB  - The Authors report their experience matured during the last decade in the
      Institute of III Surgical Clinic of the University "La Sapienza" in Rome,
      relatively to 174 patients operated of splenectomy of which 8 for not parassitair
      benign cystic pathology. After the nosologic organization of the varied types of
      cystics splenopaty is examined the different symptomatology and is discussed the
      different treatment.

PMID- 11443842
TI  - [Surgical treatment of abdominal aortic aneurysm. Factors affecting mortality and
      morbidity].
AB  - In this report, based on a 5 year experience, 76 operation were performed
      electively for intact abdominal aortic aneurysm and 55 were emergency procedure
      for ruptured aneurysm. Factor affecting mortality and morbidity in the cases are
      analysed. Three patients died of cardiac causes following elective aneurysm
      repair, a mortality rate of 3.9%. No patients died of pulmonary causes, renal
      failure or required dialysis. No patient developed a graft infection, stroke or
      intestinal ischemia. Mortality rates for surgical repair of ruptured AAA averaged
      32% and the principal cause of death is cardiac disease (50%). The second cause
      is renal failure. Declining of operative mortality for intact aortic aneurysm is
      related to earlier diagnosis using non invasive methods and correct preoperative
      study.

PMID- 11443843
TI  - [Antibiotic and immunostimulating prophylaxis in colorectal surgery].
AB  - The Authors, after considering post-operatory sepsis as cause of failures and as
      an important economic damage, make among them a distinction according to the
      arising area and to the seriousness of their manifestations. They, later,
      describe corrective and prophylactic measures which in colo-rectal surgery ase
      campulsory assumptions for sepsis prevention. After relating their experience,
      Authors reaffirm short-term protocol validity and point out validity of
      alternation of large spectrum molecules in order to avoid possible arising of
      bacterial resistances.

PMID- 11443844
TI  - Laparoscopic adrenalectomy. Personal experience in 78 patients.
AB  - Laparoscopic adrenalectomy has proved to be the technique of choice for the
      treatment of benign pathologies of the adrenals and also for the treatment of
      isolated adrenal metastases, especially arising from lung tumor, but it shouldn't
      be performed for primitive adrenal carcinoma. The harmonic scalpel is very useful
      for laparoscopic adrenalectomy showing a significant reduction in operative time.
      The Authors retrospectively investigated 78 laparoscopic adrenalectomies
      performed from April 1995 to April 2000 using a transperitoneal approach with the
      patient on a lateral position as suggested by Gagner. Special care was taken to
      improve the surgical approach to the adrenals also by means of new technological
      devices as the Harmonic scalpel. The 78 laparoscopic adrenalectomies were
      performed in 70 cases for benign neoplasms: incidentalomas 24, Cushing's disease
      16, Conn's disease 20, pheochromocytomas 9, myelolipoma 1. In the remaining 8
      patients laparoscopic adrenalectomy was performed in 7 cases for isolated adrenal
      masses (5 metastases, 2 adenomas) in neoplastic patients, and in 1 patient for a
      preoperatively diagnosed adrenal carcinoma. Patients operated for functioning
      neoplasms had all remission or improvement of symptoms and humoral parameters;
      patients operated for isolated adrenal metastases showed this survival: 3
      patients 3 years asymptomatic and disease free, 1 patient 18 months, and 3
      patients are still alive and healthy after 6-12-15 months. A fast onset of local
      recurrence was seen in a patient operated for a preoperatively diagnosed adrenal
      carcinoma. We analyzed the operating time dividing the patients in three groups:
      a) 14 patients operated in the first semester of 1998 when we completed the
      training curve (average operative time 120.7 minutes); b) 14 patients operated
      from 1998-1999 (average operative time 118 minutes); c) the last 14 patients
      (operated from December 1999 to April 2000) where surgery was performed using the
      Harmonic scalpel (HS) (average operative time 94 minutes). The analysis of the
      average operative time comparing groups B and C using T-Student Test showed a
      significant reduction (p = 0.004). The morbility rate was 2.6%, mortality 1.3%,
      and a conversion rate of 2.6%. Laparoscopic approach results to be an extremely
      reliable procedure also for the treatment of incidentalomas up to 4-5 cm in which
      the incidence of adrenal carcinoma is about 13%. Doubts may yet result for the
      treatment of adrenal carcinomas preoperatively diagnosed. When laparoscopic
      adrenalectomy in performed using HS the operative time is significantly reduced
      and surgery is easier.

PMID- 11443845
TI  - [Bilateral hernioplasty: sonographic study of prosthetic integration as a
      function of fixation to the hernia opening].
AB  - The Authors report in this paper the outcomes of a post-operative study based on
      echo and echo-color imaging in 10 patients who underwent surgery for bilateral
      groin hernia. On both sides the operation was performed with a "patch and plug"
      implantation, according to the Rutkow technique. On right sides the polypropilene
      mesh was fixed to the inguinal orifice with cardinal stitches, while on left
      sides the mesh was shaped and spreaded on the orifice without any fixation. The
      U.S. postoperative pictures, performed up to 30 th p.o. day, showed a better
      stretching of the unfixed meshs, probably owed to a better adapting capability of
      the free mesh inside the tissues in standing position. The Authors consider
      significative the correlation between images showing in 7 patient's right sides
      little irregularities in mesh display, with presence of thin liquid filled
      spaces, and the moderate postoperative pain, that occurred in the same side in 6
      of them.

PMID- 11443846
TI  - [Endoscopic obstruction treatment].
AB  - The Authors reported the last year personal experience of disobstruction
      endoscopic therapy; they described therefore an examination of the several
      techniques proposed from the international literature and in particular dwell
      upon laser-therapy and airway stents implantation. They emphasized the treatment
      importance, mostly palliative, but the effective symptomatology improvement due
      to airway obstruction, bleeding, pain and secretions retenction. They emphasize
      finally the necessity of a careful and scrupulous patients selection for
      disobstruction endoscopic therapy.

PMID- 11443847
TI  - [Endoscopic treatment of non-neoplastic cholestasis].
AB  - Now, draining the cholestasis by endoscopic way is a safe and effective solution.
      The most of Authors think that the non neoplastic cholestasis find her
      substantial solution by endoscopic methodology. We reported the most important
      endoscopic techniques used in these cases, especially the papillosphincterotomy,
      the pneumatic dilatation and the placing of endoprosthesis.

PMID- 11443848
TI  - Genetic disorders of endocrine neoplasia. Introduction..

PMID- 11443849
TI  - Multiple endocrine neoplasia type 2: clinical aspects.

PMID- 11443850
TI  - von Hippel-Lindau disease: genetic and clinical observations.

PMID- 11443851
TI  - Hamartoma and lentiginosis syndromes: clinical and molecular aspects.
AB  - The classic hamartoma syndromes and the related conditions discussed in this
      chapter show varying degrees of phenotypic and genetic overlap. Knowledge of the
      susceptibility genes underlying their phenotypes has provided additional
      information for the classification of these syndromes. Germline PTEN mutations
      appear to cause both CS and BRR. These two syndromes are therefore likely to be
      different manifestations of a single disease with variable expression. It has
      been suggested that PTEN mutation-positive CS and BRR should be grouped as a
      single entity for clinical purposes and classified as the 'PTEN hamartoma-tumour
      syndrome' [111]. Germline PTEN mutations are unlikely to cause JPS. However,
      germline SMAD4 mutation, especially a well-described 4-bp deletion, can be used
      to confirm a clinical diagnosis of JPS. Like the hamartoma syndromes, the
      lentiginoses also show substantial clinical overlap; it remains to be seen
      whether this is reflected in the molecular pathways that are involved in the
      pathogenesis of these syndromes. Given that the degree and type of cancer
      susceptibility between the hamartoma and lentiginosis syndromes is different,
      clarification of these syndromes at the molecular level is predicted to allow
      directed cancer surveillance. The molecular story is still evolving with regards
      to aspects of genetic heterogeneity, signalling pathways and the manner in which
      these hamartoma genes function in the development of their respective syndromes.
      It is likely that in all of these syndromes, tumours develop against a background
      created by loss of the growth-suppressive function of their susceptibility gene
      via mechanisms including disruption of the cell cycle and the activation of anti
      apoptotic pathways.

PMID- 11443852
TI  - Identification and characterization of disease-related genes: focus on endocrine
      neoplasias.

PMID- 11443853
TI  - Clinical and molecular aspects of multiple endocrine neoplasia type 1.

PMID- 11443854
TI  - Hereditary endocrine neoplasias: fundamental insights and the practice of
      clinical cancer genetics.

PMID- 11443855
TI  - Multiple endocrine neoplasia type 2: molecular aspects.

PMID- 11443856
TI  - EBV and malignant lymphoma with special emphasis on pyothorax-associated
      lymphoma.

PMID- 11443857
TI  - AIDS lymphoma: its virological aspects.

PMID- 11443858
TI  - Replication licensing of the EBV oriP minichromosome.
AB  - The latent EBV genome may persist in the integrated form as well as the circular
      episomal form. However, most of the latent viral DNA molecules are known to exist
      in the circular episomal form, which binds to host chromosomes during mitosis.
      The DS element of oriP in the circular episomal DNA functions as a replication
      origin. As it replicates once in a single S phase, it is possible that oriP is
      regulated by the cellular replication licensing mechanism including the MCM
      family of replication licensing factors. Transient replication analysis using the
      oriP plasmid and HeLa/EB1 cells revealed that the DS element requires early G1
      phase for the next round of replication, the same cell-cycle window in which the
      replication licensing of cellular chromatin occurs. After this phase, the
      sedimentation velocity of the oriP minichromosome increases. MCM2 associates with
      the oriP minichromosome at late G1 but not at G2/M, and this association requires
      the DS element in the plasmid. The interaction of EBNA1 and the MCM proteins on
      the DS element was also suggested. These results suggested that the cellular
      licensing mechanism controls the replication from oriP. This also suggested a
      similarity in the replication machinery of the cellular chromatin and the latent
      EBV genome. In addition to DS-dependent replication, the EBV genome replicates in
      a manner independent of the DS element in several cultured cell lines. The DS
      dependent replication is likely to be suppressed in these cell lines by the
      expression of other viral proteins. In contrast, EBV-positive Burkitt's lymphoma
      and circulating EBV-infected B cells express only EBNA1 or both EBNA1 and LMP2.
      DS-dependent replication may play a major role in these EBNA1-only cells, and the
      licensing regulation of oriP is important for maintenance of the EBV genome
      during this latent period of the viral life cycle. EBNA1 is required for
      efficient nuclear retention and partitioning of oriP-carrying plasmid by its
      binding to the FR element, thus providing stable persistence of the latent EBV
      genome during cell division. The copy number of latent EBV DNA molecules in B
      cell lines remains fairly constant during multiple passage in culture. However,
      very little is known about the mechanism by which the viral DNA molecules are
      equally segregated into daughter cells. To understand the mechanisms responsible
      for stable nuclear retention and partitioning of the latent viral genome, it is
      essential to analyze the episomal and integrated viral DNAs at a single-cell
      level by FISH and other techniques.

PMID- 11443859
TI  - Role of Epstein-Barr virus in Burkitt's lymphoma.
AB  - We established an in vitro system representing BL-type EBV infection, which is
      characterized by expression of EBNA1, EBER, BARF0, and LMP2A, and absence of
      EBNA2 and LMP1 expression (Shimizu et al. 1994; Komano et al. 1998). Comparison
      of EBV-positive and -negative Akata cell clones revealed that EBV contributes to
      the malignant phenotype and resistance to apoptosis. This is clear evidence that
      EBV is not a passenger and plays a role in BL. Moreover, we found that EBERs are
      responsible for these phenotypes (Komano et al. 1999). In the transfection study,
      EBER-expressing Akata cell clones restored the malignant phenotype, resistance to
      apoptosis and upregulated expression of bcl-2 protein to a level comparable to
      the restoration rate of EBER expression compared with EBV-reinfected cell clones.
      Many RNAs are known to have catalytic functions; however, there has been no
      report describing an oncogenic RNA. This is the first paper that provides
      evidence that RNA polymerase III-transcribed virus-encoded small RNAs affect the
      malignant phenotype and resistance to apoptosis. Like Akata cells (Takada et al.
      1991), all the BL cells possess a chromosomal translocation involving the c-myc
      locus, which results in constitutive activation of the c-myc gene (Klein 1981).
      In mammalian cells, deregulated expression of c-myc has been shown to contribute
      not only to tumorigenesis (Land et al. 1983) but also to induce apoptosis (Askew
      et al. 1991; Evan et al. 1992; Milner et al. 1993). Therefore, BL cells are
      predisposed to c-myc-induced apoptosis. Our data imply that EBV infection would
      upregulate expression of bcl-2 protein to protect cells from c-myc-induced
      apoptosis, and to allow c-myc to exert its oncogenic functions (Vaux et al. 1988;
      Brito-Babapulle et al. 1991; Bissonnette et al. 1992; Fanidi et al. 1992; Karsan
      et al. 1993; Mohammad et al. 1993; Oltvai et al. 1993; Marin et al. 1995). In
      this way bcl-2 might cooperate with c-myc in the development of BL (Fig. 5).

PMID- 11443860
TI  - EBV regulates c-MYC, apoptosis, and tumorigenicity in Burkitt's lymphoma.

PMID- 11443861
TI  - Epstein-Barr virus infection of human epithelial cells.

PMID- 11443862
TI  - Characterization of EBV-infected epithelial cell lines from gastric cancer
      bearing tissues.

PMID- 11443863
TI  - A new animal model for Epstein-Barr virus pathogenesis.

PMID- 11443864
TI  - Adoptive immunotherapy of EBV-associated malignancies with EBV-specific cytotoxic
      T-cell lines.

PMID- 11443865
TI  - EBV's plasmid replicon: an enigma in cis and trans.

PMID- 11443866
TI  - Epstein-Barr virus nuclear protein 2-induced activation of the EBV-replicative
      cycle in Akata cells: analysis by tetracycline-regulated expression.

PMID- 11443867
TI  - Two Epstein-Barr virus glycoprotein complexes.

PMID- 11443868
TI  - EBV replication enzymes.

PMID- 11443869
TI  - Pathology and molecular pathology of Epstein-Barr virus-associated gastric
      carcinoma.

PMID- 11443870
TI  - Antibody interactions with rhinovirus: lessons for mechanisms of neutralization
      and the role of immunity in viral evolution.

PMID- 11443871
TI  - A model for neutralization of viruses based on antibody coating of the virion
      surface.

PMID- 11443872
TI  - Antibody-mediated enhancement of viral disease.

PMID- 11443873
TI  - The role of the antibody response in influenza virus infection.

PMID- 11443874
TI  - Role of antibodies in controlling alphavirus infection of neurons.

PMID- 11443875
TI  - Role of mucosal antibodies in viral infections.

PMID- 11443876
TI  - The role of the complement system in virus infections.

PMID- 11443877
TI  - Intrabodies as antiviral agents.

PMID- 11443878
TI  - T-bodies as antiviral agents.

PMID- 11443879
TI  - Structural studies on antibody interacting with viruses.

PMID- 11443880
TI  - Shape and electrostatic complementarity at viral antigen-antibody complexes.

PMID- 11443881
TI  - Structural studies on viral escape from antibody neutralization.

PMID- 11443882
TI  - Affinity, complementarity, cooperativity, and specificity in antibody
      recognition.

PMID- 11443883
TI  - Mechanisms of virus neutralization by antibody.

PMID- 11443884
TI  - Skin diseases associated with HIV infection.

PMID- 11443885
TI  - Skin lesions of fibrocytic and fibrohistiocytic differentiation: a new concept
      and classification.

PMID- 11443886
TI  - Applications of molecular virology to modern dermatopathology.

PMID- 11443887
TI  - Clinicopathological differential diagnosis of drug-induced toxic epidermal
      necrolysis (Lyell's syndrome) and acute graft-versus-host reaction.

PMID- 11443888
TI  - Histopathology of Spitz naevi and "Spitzoid" melanomas.

PMID- 11443889
TI  - New concepts in cutaneous B-cell lymphomas.

PMID- 11443890
TI  - Clinical and prognostic significance of molecular studies in cutaneous T-cell
      lymphoma.

PMID- 11443891
TI  - Carbohydrate expression in the intestinal mucosa.
AB  - The understanding of mechanisms responsible for alterations in mucin synthesis
      and secretions is essential in elucidating the aetiology of intestinal disorders.
      The existence of distinct mucins and M-cell transport mechanisms, and their
      beneficial effects, have long been recognised. Since nutritional and bacterial
      factors alter the mucin characteristics and are relevant to planning preventative
      strategies for intestinal diseases, the studies described in this monograph were
      designed to test the hypothesis that mucin composition and endocrine status of
      the intestinal tract are altered by dietary constituents and microbial flora. A
      study of gut-associated lymphoid tissue (GALT) was undertaken to test the
      hypothesis that lymphocyte-epithelial interactions influence the glycosylation of
      cells overlying Peyer's patches. The effects of diet and microbial flora were
      analysed by comparing the data from male Wistar germ-free rats, with conventional
      or human flora. Such rats were fed either a commercial diet, containing crude
      fibre, or a purified diet. Bone marrow transfers from syngeneic Balb/c mice to
      severe combined immunodeficient (SCID) mice were made to induce the formation of
      GALT. A comparison was made of the glycoconjugate profile of Peyer's patches in
      the guts of mice and humans. The results of the study showed that feeding a fibre
      rich diet to germ-free rats resulted in increased villus-crypt lengths, decreased
      carboxylated mucin content of goblet cells, increased N-acetylglucosamine and
      sialic acid residues in the surface goblet cells, and a reduction in the number
      of endocrine cells in the small intestine. The lectin markers revealed M-cell
      development in the dome epithelium of the reconstituted SCID mice. Mouse M cells
      were labelled by fucose-specific lectins but in human Peyer's patches no distinct
      M-cell-staining pattern was observed. CONCLUSIONS: (1) the interactions between
      diet and flora alter the mucosal architecture and the activity of endocrine
      cells; (2) the dietary changes are influential in modifying the epithelial mucin
      predominantly in the small intestine while the microbial flora influences the
      mucosal architecture predominantly in the large intestine; (3) the use of bone
      marrow transplantation from syngeneic mice into SCID mice along with lectin
      markers for M cells can be used to study the histogenesis of Peyer's patches; (4)
      the distinct differences between mouse and human Peyer's patches suggest that
      when considering cell surface glycoconjugates as target molecules appropriate
      lectin should be used for each species. A future challenge in intestinal
      epithelial cell biology is identifying the nature and distribution of cell
      surface receptors for specific dietary components and bacteria.

PMID- 11443892
TI  - [Chemistry of medicinal plants (review)].
AB  - Data on the chemical composition related to synthesis of physiologically active
      substances (alkaloids, terpenoids, glycosides, phenolic compounds, etc.), and
      accumulation of individual elements or groups of five to ten elements (e.g., Cr,
      Co, Mn, and Zn) in medicinal plants were reviewed. Chemical features of medicinal
      plants serve as an integral determinant of their species specificity and
      pharmacological properties and enabling their wide use in medical practice. The
      relationship between the synthesis of physiologically active substances and
      accumulation of elements is mediated by several levels of molecular regulation.

PMID- 11443893
TI  - [Immunomodulatory properties of 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate
      and search for its new derivatives].
AB  - A strong immunomodulatory effect of 2-C-methyl-D-erythritol-2,4
      cyclopyrophosphate (MEC) responsible for the survival of bacteria was shown on
      isolated macrophages and in experimental infections in mice (typhoid and
      tularemia). Derivatives of MEC were found by 1H-NMR spectroscopy under stress
      conditions in colorless mutants of the bacteria and isolated to be subsequently
      purified and used for modulation of the immune system of animals.

PMID- 11443894
TI  - [Effect of inhibitors of enzymatic DNA methylation on the formation of
      reproductive structures and carotenoid production in Neurospora crassa].
AB  - The effect of inhibitors of DNA methylation on light-sensitive developmental
      stages of the filamentous fungus Neurospora crassa was studied. Under conditions
      of nitrogen starvation, when blue light induced protoperithecia development and
      inhibited conidia formation, 5-azacytidine (3-300 microM) inhibited
      protoperithecia formation and stimulated conidia formation (a 700-fold increase
      after light induction). After treatment of the mycelium with 5-azacytidine, the
      protoperithecia formation was accompanied by inversely proportional changes in
      the formation of conidia, both in the dark and after illumination. In the
      mycelium cultivated on the Vogel's medium, 5-azacytidine (up to 30 microM) and
      methotrexate (up to 3 microM) stimulated the light-induced carotenoid synthesis
      by 30%, whereas higher concentrations of these agents were toxic to carotenoid
      synthesis and growth.

PMID- 11443895
TI  - [Oxidation of indole and its derivatives by heme-independent chloroperoxidases].
AB  - Indole, indolylacetic acid, and tryptophan were oxidized by cloroperoxidases
      isolated from strains of Streptomyces lividans and Pseudomonas pyrrocinia. Indigo
      (indoxyl), isatin, and anthranilic acid (intermediate products of oxidative
      degradation of indole and indole derivatives) were extracted from the reaction
      medium.

PMID- 11443896
TI  - [Study of the lytic activity of actinomycetes isolated from various soils in
      Georgia].
AB  - The lytic activities of 310 cultures from the Collection of Actinomycetes of the
      Institute of Biochemistry and Biotechnology, National Academy of Sciences of
      Georgia, were studied; 18% of these strains appeared capable of lysing the yeast
      cell wall. The active producer of the enzyme was selected. This culture was
      isolated from chestnut soil in Gardabani raion (Central Georgia). Its cultural
      morphological, biochemical, and antagonistic properties allowed the culture to be
      ascribed to the species Geodermatophilus obseurus Luedemann, 1968. The maximal
      lytic activity under deep cultivation conditions, exceeding twofold the activity
      of Actinomyces griseinus, was observed during the logarithmic growth phase.

PMID- 11443897
TI  - [Rugulosuvines A and B--diketopiperazine alkaloids from Penicillium rugulosum and
      Penicillium piscarium fungi].
AB  - Two diketopiperazine alkaloids, rugulosuvines A and B (tryptophan and
      phenylalanine are precursors), were isolated and purified from the culture liquid
      of Penicillium rugulosum VKM F-352 and Penicillium piscarium VKM F-325 fungi.
      Physical and physicochemical studies showed the absolute structure of
      rugulosuvine A. The absolute structure of rugulosuvine B was demonstrated to be
      similar to that of rugulosuvine A.

PMID- 11443898
TI  - [Dependence of the activity of L-amino acid oxidase in the fungus Aspergillus
      niger R-3 on the source of nitrogen in growth media].
AB  - Various populations of peroxisomes in cells of Aspergillus niger R-3 were formed
      under the growth in media containing 0.5% glucose and various sources of nitrogen
      (1/4 of optimal concentrations of (NH4)2SO4, L-alanine, and L-methionine).
      Different levels of of L-amino acid oxidase activity were found in these
      populations of peroxisomes.

PMID- 11443899
TI  - [Isolation of peptide antibiotic virginiamycin components and selection of their
      producer Streptomyces virginiae].
AB  - A method for chromatographic separation and quantitative determination of
      individual components of the antibiotic virginiamycin, produced by
      microbiological synthesis (Streptomyces virginiae strain 147), is described. The
      components, M1-2 and S1-5, were isolated from fermentation broth and identified
      by HPTLC and HPLC (the results obtained using the two methods correlate well with
      each other). Conditions of culturing of the producer and compositions of
      nutritive media were optimized. Using UV irradiation as a mutagenic factor, the
      producer was selected for increased level of synthesis of the antibiotic; this
      was achieved by inducing mutations that impart resistance to virginiamycin and
      meta-fluorophenylalanine, an analog of phenylalanine.

PMID- 11443900
TI  - [Biosynthes of polyketide antibiotics by various actinomycin producing
      Streptomyces species].
AB  - A collection of actinomycin-producing Streptomyces strains, their variants with
      different levels of antibiotic biosynthesis, and recombinant strains were
      screened in order to select new strains that produce polyketide antibiotics.
      Screening with the use of the cloned act gene encoding a component of
      actinorhodin polyketide synthase (PKS) multienzyme complex from Streptomyces
      coelicolor revealed that many strains tested can synthesize polyketide
      antibiotics along with actinomycins. A relationship between biosynthetic pathways
      of actinomycins and polyketides is discussed.

PMID- 11443901
TI  - [Microelements preparations obtained during processing of natural flint affect
      the physiology and biochemistry of bifidobacteria].
AB  - Microelement preparations obtained in the course of processing of flint powder
      stimulate the biological activity of Bifidobacterium adolescentis 94 BIM, grown
      on complex and synthetic nutritive media. The composition of the microelement
      preparations differed in the content of cations and anions. Introduction of the
      preparations into the cultures of physiologically active or anabiotic forms of
      bifidobacteria changed the parameters of exponential growth: compared to
      controls, the cultures were characterized by increased specific growth rate and
      decreased generation time. In the presence of microelements, the development of
      populations of bifidobacteria was associated with more pronounced accumulation of
      metabolic products (acetate, lactate, and ethanol). Introduction of microelement
      preparations increased the rate of synthesis of the extracellular proteinase
      (maximum content of the enzyme was observed after 3 h, whereas control cultures
      attained this level only after 6 h).

PMID- 11443902
TI  - [The respiratory activity of Rhodococcus rhodochrous M8 cells producing nitrile
      hydrolyzing enzymes].
AB  - The respiratory activity of Rhodococcus rhodochrous M8 cells containing nitrile
      hydratase and amidase was studied in the presence of nitriles and amides of
      carbonic acids. Culturing of cells with acrylonitrile and acrylamide yielding
      their maximum respiratory activity was studied. The optimum conditions for
      measurements and maintenance of respiratory activity were found. Curves for the
      linear concentration dependence of cell respiratory activity on 0.01-0.5 mM
      acrylonitrile, 0.025-1.0 mM acetonitrile, and 0.01-0.1 mM acrylamide were
      plotted. The selectivity of cell respiratory activity for some substrates was
      analyzed.

PMID- 11443903
TI  - [Structure and characteristics of glucomannans from Eremurus iae and
      E.zangezuricus: detection of acetyl group localization in macromolecules].
AB  - Water-soluble glucomannans from roots of Eremurus iae and E. zangezuricus were
      studied. These polysaccharides were shown to contain 28.8; 69.0, and 2.2% (E.
      iae) and 22.6; 74.8, and 2.6% (E. zangezuricus) of D-glucose, D-mannose and
      acetyl groups, respectively. Their IR spectra were identical and revealed the
      presence of 1,4-beta-glycosidic bonds and ester carbonyl groups. 13C-NMR
      spectroscopy revealed both polysaccharides to be linear partially acetylated 1,4
      beta-D-glucomannans. Acetyl groups substituted C-2- and C-3-hydroxyls of
      mannopyranose residues. Comparison of 13C-NMR data and the results of correlation
      analysis enables a conclusion to be made that acetyl groups can substitute no
      more than one OH-group in the mannopyranosyl residue. [alpha]D = -34.0 degrees,
      [eta] and molecular weights (MW) for E. iae polysaccharide were determined to be 
      34.0, 6.5 dl/g, and 265.5 kDa, respectively, and for E. zangezuricus
      polysaccharide -38.2, 5.4 dl/g, and 233.5 kDa, respectively. A correlation
      between intrinsic viscosities of polysaccharides and their molecular masses
      determined by HPLC was revealed.

PMID- 11443904
TI  - [Enzymatic proteinaceous hydrolyzate from the processing waste of the Iceland
      scallop Chlamys islandica].
AB  - Dry enzymatic hydrolyzate was derived from the protein containing wastes of the
      Iceland scallop fishery using the complex of proteinases from the king red crab
      hepatopancreas. The finished product contains not less than 80% of free amino
      acids and the lowest peptides. Leucine, isoleucine, arginine, lysine and aspartic
      acids account for to 50% of free amino acids. The applicability appraisal of
      proteinaceous hydrolyzate from the wastes of the Iceland scallop fishery to use
      them as the constituents in the nutrient medium for microorganisms was conducted.
      The approbation of hydrolyzate in the composition of nutrient medium on the test-
      cultures indicated the high sensibility and germinating capacity of
      microorganisms.

PMID- 11443905
TI  - [Mineral composition of cultured Ginseng cells].
AB  - The contents of macroelements and microelements in ginseng roots and callus
      cultures was determined by atom absorption spectroscopy. Ginseng cells and
      tissues were shown to accumulate considerable amounts of microelements. The
      content of six of eleven mineral components studied (K, Ca, Na, Mo, Mn, and Cr)
      in callus cultures was higher than that in roots of agricultural ginseng plants.
      We revealed good correlations between the contents of microelements (K, Ca, and
      Mg), as well as between the concentrations of macroelements (Mo, Li, Cu, and Cr)
      in ginseng cultures. The ability to accumulate elements varied between ginseng
      species, which was probably related to their genetic features. Our findings
      indicate that cultured ginseng cells hold much promise as the source of
      microelements.

PMID- 11443906
TI  - [Isolation of genetically modified potato plant containing the gene of defensive
      peptide from Amaranthus].
AB  - The plants of potato (Solanum tuberosum L., var. Desire) have been transformed
      with a pH22Kneo vector carrying the gene ac2, encoding the fungicidal peptide
      (defensin) from the seed of amaranth (Amaranthus caudatus L.). The transformation
      involved co-cultivation of potato stem explants (excised from aseptically grown
      plants) and Agrobacterium tumefaciens on solid MS medium. Factors affecting in
      vitro regeneration of the explants and the transformation efficiency were
      optimized. Regenerated potato plants harboring the amaranth defensin gene were
      selected by two traits, growth and ability to form roots on kanamycin
      supplemented MS medium. The transgenic state was confirmed PCR analysis of ac2 in
      tissues of the kanamycin-resistant plants. The transgenic organisms thus obtained
      differed from the original ambiol-treated plants in growth patterns and proton
      translocation across the plasma membrane of the tuber cells.

PMID- 11443907
TI  - [Effect of arachidonic acid on potato tubers during storage].
AB  - Potato (Solanum tuberosum L.) tubers were treated with various concentrations
      (10(-9) to 10(-4) M) of the biogenic elicitor arachidonic acid during the period
      of storage (from October to July). The data showed that the resistance-inducing
      concentration of arachidonic acid was 10(-6) M in autumn and 10(-9) M in spring.
      Possible causes of the change in the immunizing concentration of arachidonic acid
      during storage of potato tubers are discussed.

PMID- 11443908
TI  - [Lipids of microorganisms from the family Vibrionaceae causing diseases in
      fishes].
AB  - Lipid fractional and fatty acid compositions of microorganisms from the genera
      Aeromonas, Pseudomonas, and Vibrio (the family Vibrionaceae), causing diseases of
      different fish species, were studied. Motile aeromonads and vibrios displayed
      higher relative contents of membrane lipids and oleic acid and lower relative
      contents of storage lipids compared with immotile aeromonads and pseudomonads,
      which is connected with the activities of their movements. Immotile aeromonads
      and vibrios exhibited higher levels of polyunsaturated fatty acids and higher
      absolute phospholipid contents compared to motile aeromonads and pseudomonads.
      This is likely to be related to host specificity of these bacteria and reflects
      the specific patterns of fatty acid compositions of the infected fish (salmonid
      and cyprinid) tissues.

PMID- 11443909
TI  - [Adaptive changes in fatty acid compositions of whitefish Coregonus lavaretus L.
      tissue lipids induced by anthropogenic factors].
AB  - Adaptive processes in the body of whitefish (Coregonus lavaretus L.) caused by
      anthropogenic effects on aquatic systems were studied. It was demonstrated that
      the content of fatty acid acyls correlated with the water pollution level. The
      role of a decrease in the content of arachidonic acid in fish reproduction under
      adverse conditions is discussed. It is underlined that the quantitative
      alterations in the gonad and liver fatty acid patterns are unidirectional. A
      compensatory character of the changes discovered is hypothesized.

PMID- 11443910
TI  - [Use of highly dispersed materials for culturing and isolation of granular
      Agrobacterium radiobacter preparations ].
AB  - The effects of synthetic and natural high-dispersion materials on the growth of
      Agrobacterium radiobacter were studied. Natural minerals montmorillonite and
      palygorskite (10 g/l nutrient medium) were more potent than high-dispersion
      silica and its modified forms in stimulating growth of Agrobacterium radiobacter.
      The interaction of Agrobacterium radiobacter with clay minerals increased the
      survival rate of bacteria at supraoptimal temperatures. We elaborated new
      granular bacterial preparation, which enhanced the productivity of cucumbers by
      12-15%.

PMID- 11443911
TI  - [The effect of soil inoculation with microbial pesticide destructors on plant
      growth and development].
AB  - Soil inoculation with liquid cultures of Bacillus megaterium 501 and Exophiala
      nigrum A-29 capable of degrading several organophosphorus pesticides accelerated
      growth and development of experimental plants, formation of their generative
      organs, and improved their productivity. This was particularly observed under
      stress plant growth conditions on phytotoxic peach substrates. The microorganisms
      inoculated can probably degrade phytotoxins present in soils, thereby favoring
      the plant development.

PMID- 11443912
TI  - [Effect of thermolability of milk proteins on ion distribution in two-phase
      system of skimmed milk-water-salt].
AB  - Significant increases in concentrations of bivalent metals (Ca2+, Mg2+, and Cd2+)
      in the protein phase were observed after acidification (pH 4.7) of skimmed milk
      preheated at 95 degrees C for 90 min. The increase was caused by denaturation of
      milk whey proteins and formation of protein-protein and protein-carbohydrate
      aggregates. Preheating did not influence the distribution of nitrate ions in the
      two-phase system.

PMID- 11443913
TI  - [Introduction to plant genomics].
AB  - The success in complete sequencing of "small" genomes and development of new
      technologies which sharply accelerate processes of cloning and sequencing made
      real an intensive development of plant genomics and complete sequencing of DNA of
      some species. It is assumed that the success in plant genomics will result in
      revolutionary changes in biotechnology and plant breeding. However, the enormous
      size of genomes (tens of billions bp), their extraordinary enrichment in
      repetitive sequences, and allopolyploidy (the presence in a nucleus of several
      related but not identical genomes) force us to think that only few "basic" will
      undergo complete sequencing, whereas the genome investigations in other species
      will follow principles of comparative genomics. By the present time, complete
      sequencing of the Arabidopsis genome (125 Mbp) is completed and that of the rice
      genome (about 430 Mbp) is close to its end. Studying other plant genomes,
      including those economically valuable, already began on the basis of these
      investigations. Peculiarities of plant genomes make extraordinarily important the
      knowledge on plant chromosomes which, in its turn, requires expansion of
      investigations in this direction and development of new chromosome technologies,
      including the DNA-sparing methods of high-resolution banding.

PMID- 11443914
TI  - [Angiogenin and its role in angiogenesis].
AB  - The review is devoted to angiogenin, one of the factors that induce formation of
      blood vessels, which is unique among them in that it is a ribonuclease.
      Consideration is given to the tertiary structure of human angiogenin; the
      catalytic and cell-receptor binding sites, their significance for angiogenic
      activity; the human angiogenin gene structure, chromosomal localization, and
      expression; the specificity of angiogenin as a ribonuclease and abolishment of
      protein synthesis; the nuclear localization of angiogenin in proliferating
      endothelial cells and its significance for angiogenic activity; angiogenin
      binding to a cell-surface actin as a plausible mechanism of inducing
      neovascularization (enhancement of plasminogen activation by actin with
      angiogenin, stimulation of the cell-associated proteolytic activity by
      angiogenin; promotion of the cultured cells invasiveness); modulation of
      mitogenic stimuli in endothelial, smooth muscle, and fibroblast cells by
      angiogenin. The importance of angiogenin as an adhesive molecule for endothelial
      and tumor cells is discussed too, as well as the modulation of tubular
      morphogenesis by bovine angiogenin, prevention of tumor growth in vivo by
      angiogenin antagonists, prospects of the use of angiogenin and angiogenin
      encoding recombinant plasmids and vaccinia virus in therapeutic practice.

PMID- 11443915
TI  - [First advances in molecular endocrinology obtained using the Cre/LoxP system].
AB  - The insulin-like growth factor I (IGF-I) is produced in the liver and is
      considered mediating the effect of the growth hormone (GH). However, a knock-out
      only in liver IGF-I slightly disturbs the growth and development of mice. Such
      mice develop insulin resistance of various organs, including muscles. A knock-out
      in the liver insulin gene also results in insulin resistance. Selective
      inactivation of the gene for glucokinase (a target of insulin) in pancreatic
      islets or in the liver suppresses insulin secretion in the pancreas.

PMID- 11443916
TI  - [Presence of MIR-elements in the complete nucleotide sequence of human chromosome
      22].
AB  - The location of mammalian interspersed repeats (MIRs) and their density have been
      determined in the complete nucleotide sequence of human chromosome 22. The
      approach developed by us has allowed detection of 9675 MIRs at a statistically
      significant level, which by 15% exceeds the MIR number revealed by all previous
      approaches. It has been demonstrated that a considerable amount of MIRs missed by
      the algorithms applied earlier occurs in known DNA sequences of the human genome.
      The study of the MIR density revealed substantial irregularity of their
      distribution along the chromosome. The data on the MIRs thus found and the
      computer program searching for diverged sequences are available by E-mail:
      katrin2@mail.ru or katrin22@mtu-net.ru.

PMID- 11443917
TI  - [Gene for structural proteins of the SMC family in the common vole Microtus
      arvalis].
AB  - Genes for four subfamilies of SMC (structural maintenance of chromosomes)
      proteins have been isolated from the genome of a common vole Microtus arvalis.
      The high degree of homology between representatives of each SMC protein subfamily
      of different classes of organisms has been demonstrated. The full-sized copy of a
      mammalian gene encoding SMC4 protein has been isolated and analyzed for the first
      time. The SMC proteins enter into the composition of complexes responsible for
      cohesion of sister chromatids, formation of mitotic chromosomes, recombination,
      DNA repair, and regulation of gene expression. We discuss the possible
      participation of the SMC proteins in inactivation of the X chromosome in
      mammalian females. Common voles of genus Microtus group "arvalis" serve a unique
      model for the study of the inactivation process.

PMID- 11443918
TI  - [Analysis of the structure-functional features of a highly-repeating centromere
      sequence from the Fringilla coelebs L. (Aves: Passeriformes) genome].
AB  - A highly repetitive centromeric Fringilla coelebs PstI (FCP) element was cloned
      and sequenced. The FCP tandem repeats with unit 505 or 506 nt accounted for about
      0.9% of the entire genome and had 57% GC. Direct genomic sequencing with FCP
      specific primers and ThermoFidelase 2A revealed the consensus sequence and the
      five most common single-nucleotide polymorphisms (SNPs) for the FCP unit. FCP may
      be transcribed and may play a role in spatial arrangement of the genome.

PMID- 11443919
TI  - [Insertion-deletion polymorphism of the serotonin carrier gene and evaluation of
      neurotism as a temperament trait in patients with affective disorders and
      mentally healthy people].
AB  - Some studies associate the insertion/deletion polymorphism of the serotonin
      transporter (5-HTT) gene with anxiety-related personality traits in mentally
      healthy people, the short (s) allele being associated with a higher neuroticism
      score. The 5-HTT genotype and neuroticism score were established for 114
      affective patients, 87 healthy relatives of endogenous psychosis patients, and
      for 156 mentally healthy people without familial psychiatric history. The effects
      of sex and age on the association between the two parameters was studied.
      Neuroticism proved to be not associated with the 5-HTT genotype.

PMID- 11443920
TI  - [Connection of HindIII-polymorphism of the lipoprotein lipase gene with risk of
      developing myocardial infarct].

PMID- 11443921
TI  - [Mapping allelic deletions on the short arm of human chromosome 3 in kidney
      neoplasms].
AB  - Allelic deletions along the short arm of human chromosome 3 were mapped in 57
      pairs of DNA samples from tumor and normal tissue of renal carcinoma patients in
      order to locate potential tumor suppressor genes. Twenty highly polymorphic
      microsatellite markers were used for deletion mapping. Allelic deletions were
      found in most of the samples (91%). Extended terminal deletions (56%) prevailed
      over shorter internal and multiple deletions and dominated (65%) in the most
      aggressive histopathological kidney cancer subtype, clear-cell carcinoma.
      Frequency analysis of loss of heterozygosity allowed detection of the human
      chromosome 3 regions most essential for renal carcinomas: the region adjacent to
      the gene VHL (3p26-p25), the region of homozygous deletions AP20 (3p22-p21.33),
      and a new region between markers D3S2420 and D3S2409 (3p21.31, 2.2 Mbp).

PMID- 11443922
TI  - [Removal of the 3'- and 5'-untranslated region amplifies expression of the
      erythropoietin gene in mammalian cells].
AB  - The effect of the 5T- and 3T-untranslated regions (UTR) of human erythropoietin
      gene (gEpo) on its expression in mammalian cells was investigated. 5T-UTR
      deleted, 3T-UTR-deleted, and 5T,3T-UTR-deleted gEpos were transfected into COS-7
      cells, and the amount of transiently expressed Epo was measured. Cells
      transfected with the 5T,3T-UTR-deleted gEpo showed the highest expression, 2.6
      times that with wild-type gEpo. Northern blot analysis indicated that the
      enhanced expression of 5T,3T-UTR-deleted gEpo might be related with the
      transcription efficiency.

PMID- 11443923
TI  - [Features of spatial organization of the human dystrophin gene: analysis of the
      probing with endogenous topoisomerase II].

PMID- 11443924
TI  - [Isolation and identification of PACE-binding protein rpn4--a new transcription
      activator, participating in regulation of 26S proteosome and other genes].
AB  - A new upstream activating sequence (UAS) 5'-GGTGGCAAA-3' was detected in the
      promoters of 27 out of the 33 proteasomal genes and of several genes related to
      the ubiquitin-proteasomal system of Saccharomices cerevisiae. The sequence was
      termed proteasome-associated control element (PACE). Gel retardation assay
      revealed specific binding of PACE with an extracted protein. The protein (64K)
      was purified by affinity chromatography and was homogeneous by SDS-PAGE.
      Microsequencing showed that the protein is Rpn4p. The ability of Rpn4p to
      activate transcription was demonstrated with constructs containing fragments of
      the RPN5 and CDC48 gene promoters and reporter cat. Binding to PACE, Rpn4p may
      act as a common transcription factor on the proteasomal and proteasome-related
      genes.

PMID- 11443925
TI  - [Interaction of topotecan--a DNA topoisomerase inhibitor--with dual-stranded
      polydeoxyribonucleotides. I. Dimerization of topotecan in solution].
AB  - Behavior of topotecan, DNA topoisomerase I inhibitor, was studied in aqueous
      solutions by optical methods. Topotecan absorption spectra were recorded in the
      pH range 0.5-11.5 and its pKa were determined. Quantum chemical calculations were
      made for all charge states of the topotecan molecule in lactone and carboxylate
      form. The calculated absorption maxima agree well with the experimental data.
      Protonation of the topotecan D ring (pKa = 3.6) was revealed. Comparison of
      experimental and calculated data showed topotecan structure with a proton at the
      oxygen atom at C16a rather than N4 to be the most preferable. Topotecan molecules
      were shown to form dimers at concentrations above 10(-5) M. Topotecan
      dimerization is accompanied by an increase in the pKa of hydroxy group of the A
      ring from 6.5 ([TPT] = 10(-6) M) to 7.1 ([TPT] = 10(-4) M), which indicates
      participation of this group in dimer stabilization, perhaps due to intermolecular
      hydrogen bonding with N1 of the B ring of a neighboring molecule. Probable dimer
      structures were proposed. The topotecan dimerization constant was determined, K =
      (4.0 +/- 0.7) x 10(3) M-1.

PMID- 11443926
TI  - [Interaction of topotecan--a DNA topoisomerase I inhibitor--with dual-stranded
      polydeoxyribonucleotides. II. Formation of a complex containing several DNA
      molecules in the presence of topotecan].
AB  - This study is a continuation of a series of papers dealing with topotecan
      interaction with double-stranded polydeoxyribonucleotides. We showed earlier that
      topotecan molecules form dimers in solution at concentration above 10(-5) (per
      base pair). Topotecan interaction with calf thymus DNA in solutions of low ionic
      strength was studied by fluorescence, circular dichroism, and linear flow
      dichroism. The data obtained indicate that topotecan forms two types of complex
      with DNA, DNA molecules combining with each other during formation of one of
      these complexes. The association constant of two topotecan-filled DNA molecules
      with each other was estimated at 10(4) M-1 (per base pair) in 1 mM sodium
      cacodylate buffer, pH 6.8, at 20 degrees C. A possibility of modulation of DNA
      topoisomerase I activity by topotecan due to complexation with several sites of a
      supercoiled DNA molecule is discussed.

PMID- 11443927
TI  - [Change in entropy of the free polypeptide chain during formation of hydrogen
      bonds].
AB  - Formation probabilities of different hydrogen bonds between carbonyl oxygen and
      amide hydrogen were determined by Monte Carlo simulations using a computer model
      in the space of sterically allowable conformations of alanine and glycine
      oligopeptides, and the corresponding entropy losses for the peptide backbone, T
      delta S, were calculated. The model was studied at different criteria of steric
      interactions. Comparison with the data of other authors showed the values of T
      delta S to be mainly determined by overall extent and type of the state space and
      to be only slightly dependent on its energy profile. Both short-range and long
      range steric interactions were shown to prevent hydrogen bonding, especially in
      alanine peptides. In the model studied, the initiation of alpha(R)-helices is
      associated with T delta S = 8-10 kT, and prior formation of a 3/10-turn or one
      three-center H-bond does not appreciably decrease this entropy barrier.
      Elongation of the alpha(R)-helix by one residue leads to T delta S = 3.0-3.7 kT,
      the helices begin to stabilize after at least three sequential H-bonds are
      formed. The difference in the probability of insertion of Ala and Gly into the
      helix is lower than it follows from comparison of their mobility. The results
      could be explained assuming that factors different from helical H-bonds take part
      in the stabilization of the helices. One may suppose upon modeling of folding
      that even three sequential H-bonds are unable to fix the structure of a flexible
      peptide loop, while the elongation of alpha(R)-helices in the supersecondary
      helix-loop-helix structure is favorable as long as the loop conformation remains
      nearly optimal.

PMID- 11443928
TI  - [Effect of the hepatocarcinogen ortho-aminoazotoluene on induction of tyrosine
      aminotransferase by glucocorticoids in mouse liver].
AB  - o-Aminoazotoluene (OAT) suppressed more than twofold the glucocorticoid induction
      of tyrosine aminotransferase (TAT) in the liver of SWR mice, which are sensitive
      to the hepatocarcinogenic effect of OAT, but not in resistant AKR mice. The
      hormone- and DNA-binding activities of the glucocorticoid receptor (GR) were not
      affected in either line. The OAT-dependent suppression proved to be associated
      with a decrease in the DNA-binding activity of HNF3 in liver cell extracts. The
      content of the HNF3 mRNA did not change, suggesting a posttranscriptional effect
      of OAT.

PMID- 11443929
TI  - [Status of the human DNA papillomavirus in cervical tumors].
AB  - Cervical carcinoma is etiologically associated with the human papilloma virus
      (HPV), HPV 16 and HPV 18 being the most common. Viral DNA is thought to persist
      mostly in the episomal form in early tumor development, and in the integrated
      form in carcinomas. This assumption was checked with a new method that
      discriminated between RNAs transcribed from episomal and integrated HPV DNAs.
      Both forms were detected in carcinomas of Russian patients regardless of the
      disease stage. The data were verified by two other methods. RNA with sequences of
      the HPV transforming gene E7 proved to be transcribed from either DNA form. The
      results suggest that HPV integration is not crucial for carcinoma progression.

PMID- 11443930
TI  - [Variation in the nucleotide sequences of a 16S rRNA gene fragment from
      cyanobacteria from picoplankton from Lake Baika from natural samples and
      laboratory cultures].
AB  - Nucleotide sequences were determined for the 16S rRNA gene 5T-terminal regions of
      29 strains of picoplankton cyanobacteria from the lake Baikal in Russia and four
      strains from the lake Constance (Bodensee) in Germany. Sequences of a 387-bp
      region of the gene of cultivated strains designated A, B, C, D, and E had only a
      few (1-3) substitutions as compared with the 3-27 sequence of the clones obtained
      earlier by cloning from a pooled sample of Baikalian winter picoplankton. The
      specific 4-33 sequence obtained earlier from a dominant species of Baikalian
      picoplankton was not found in cultivated cyanobacteria.

PMID- 11443931
TI  - [Identification of the protease-binding domain in the N-terminal region of the
      influenza A virus matrix protein M1].
AB  - A region responsible for protease binding by influenza virus (Flu) matrix protein
      M1 was identified. Trypsin binding was attributed to the N-terminal 9-kDa
      fragment obtained by hydrolyzing M1 with formic acid. The binding was inhibited
      by monoclonal antibodies (mAb) to the N-terminal moiety and by antiserum to
      region 21-45 of M1, whereas mAb to the middle and C-terminal regions had no
      effect. Thus, the protease-binding domain (PBD) was mapped to the N-terminal
      moiety of M1.

PMID- 11443932
TI  - [Comparative study of the morphology and antigenic properties of recombinant
      analogs of a Marburg virus nucleoprotein].
AB  - The full-length gene for Marburg virus (MV) nucleoprotein (NP) was cloned in
      prokaryotic pQE32 under the control of the T5 promoter and in eukaryotic pTM1
      under the control of the promoter for T7 RNA polymerase. Recombinant NP was
      synthesized in Escherichia coli and in human kidney cell line 293 cotransfected
      with recombinant vaccinia virus vTF7-3 expressing T7 RNA polymerase. On evidence
      of electron microscopy with immune detection, recombinant NP formed tubules of
      two types in E. coli and of a single type in cell line 293. ELISA and
      immunoblotting with polyclonal and monoclonal antibodies revealed common
      antigenic determinants in recombinant NP and natural MV NP.

PMID- 11443933
TI  - [Reduction of the functional match of influenza virus hemagglutinin and
      neuraminidase after reassortation of genes].
AB  - Influenza virus A (FluA) reassortants with low-functional neuraminidase (NA) of
      subtype N1 and hemagglutinin (HA) of subtypes H2, H3, H4, and H13 display virion
      aggregation and accumulate to a lower titer because sialyl residues are not
      completely removed from virion components. Nonaggregating variants of FluA
      (H13N1) were shown to result from a mutation that reduces the HA affinity for
      sialyl substrates. Amino acid substitution K156E, which increases a negative
      charge at the edge of the receptor-binding pocket of HA large subunit (HA1), was
      revealed in two independent variants. This substitution was the only difference
      between HA1 of the original reassortant and one of its variants and, therefore,
      accounted for restoration of the functional match between HA and NA.

PMID- 11443934
TI  - [Differences in the spatial structure of an envelope protein from tobacco mosaic
      virus and its mutant, detected by tritium planigraphy].
AB  - Mutant ts21-66 of the tobacco mosaic virus (TMV) differs from the wild-type TMV
      U1 by two mutations (Ile-21-->Thr and Asp-66-->Gly) in the coat protein (CP) gene
      and in symptoms produced in infected N' plants. The CP structure in TMV-U1 and
      ts21-66 virions was probed by tritium planigraphy. Compared with the wild-type
      CP, labeling of the N-terminal region of mutant CP was half as high and suggested
      its greater shielding. A role of this CP region in virus interactions with the N'
      resistance system is discussed.

PMID- 11443935
TI  - [Isolation and identification of tyrosine kinase from the cytosolic fraction of
      bovine retinal rod outer segments].
AB  - It was shown that the cytosol fraction of bovine retinal rod outer segments
      contains three forms of tyrosine kinase. One of them was purified 171-fold to
      attain a specific activity of 1.6 nmol/min per mg protein. The isolated protein
      had a molecular weight of about 54,000 in SDS electrophoresis. It was shown that
      this protein is a tyrosine-specific protein kinase, capable of
      autophosphorylation at the tyrosine residues and restoration of kinase activity
      upon denaturation-renaturation.

PMID- 11443936
TI  - [ITS1, 5.8S and A-type ITS2 rDNA sequences from Plasmoidum vivax and development
      of a method for retrospective PCR diagnosis of malaria by stained thick blood
      smears].
AB  - Stages life cycle of the malaria parasite differ in the rate of replication and
      the structural properties of functionally active A-, S-, and O-type ribosomes.
      Regions of A-type rDNA including ITS1, 5.8S, and ITS2 from two strains of
      Plasmodium vivax with different incubation periods were amplified and sequenced.
      No substantial differences in the sequences of two strains were revealed.
      Phylogenetic analysis of the obtained and homologous sequences of ITS1 rDNA of A,
      S, and O types of P. vivax; A and S types of P. falciparum; and Cryptosporidium
      parvum, Eimeria maxima, Toxoplasma gondii as outgroup, by the maximum parsimony
      method using PAUP 4.0 revealed that divergence of ITS1 might have occurred after
      speciation and at different rates in individual lineages of the Plasmodium genus.
      Basing on the results of the analysis of orthologous sequences of P. vivax and P.
      falciparum, we developed genus- and species-specific primers for PCR diagnostics
      of malaria, as well as a one-step effective method of DNA isolation from Giemsa
      Romanovsky-stained thick blood smears. It was demonstrated that stained
      preparations could be a reliable source of plasmodial DNA, and the quality of
      preparations and storage time (10-20 years) did not interfere with the results of
      PCR analysis.

PMID- 11443937
TI  - [Synthesis of modified peptides with C-terminal alpha-amino aldehydes].
AB  - Various synthetic approaches to modified peptides with the C-terminal aldehyde
      group, capable of inhibiting a number of proteolytic enzymes belonging to the
      classes of thiol, serine, and aspartyl proteases, are considered. Both chemical
      methods, including solid phase peptide synthesis now widely used, and
      biocatalytic synthetic methods for obtaining these substances are discussed in
      detail.

PMID- 11443938
TI  - [Synthesis, immunogenicity and antigenic characteristics of the glycoprotein E
      fragments from the tick-borne encephalitis virus].
AB  - Six peptide fragments of the envelope protein E of the tick-borne encephalitis
      virus involving the predicted T-helper epitopes were synthesized. Their ability
      to induce antibodies without conjugation with any high-molecular-mass carrier was
      studied in mice of three lines. Five of six synthesized peptides exhibited
      immunogenic properties, which differed in dependence on the haplotype of
      immunized mice. The peptide binding to the antiviral antibodies was studied, and
      two peptides were revealed that demonstrated a high ability to recognize the
      viral antibodies in the horse and human sera. These peptides are promising for
      the development of diagnostic agents for the tick-borne encephalitis virus.

PMID- 11443939
TI  - [Semax and selank inhibit the enkephalin-degrading enzymes from human serum]].
AB  - A dose-dependent effect of synthetic heptapeptides Semax (Met-Glu-His-Phe-Pro-Gly
      Pro) and Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) on the enkephalin-degrading enzymes
      of human serum was demonstrated. The inhibitory effects of Semax (IC50 10 microM)
      and Selank (IC50 20 microM) are more pronounced than those of puromycin (IC50 10
      mM), bacitracin, and some other inhibitors of peptidases. Beside the
      heptapeptides, their pentapeptide fragments also possessed an inhibitory effect;
      tri-, tetra-, and hexapeptide fragments did not display such an effect. As the
      above enzymes take part in degradation of not only enkephalins but also other
      regulatory peptides, it can be assumed that one of the mechanisms of biological
      activity of Semax and Selank is related to this inhibitory activity of theirs.

PMID- 11443940
TI  - [Protein engineering of uridine phosphorylase from Escherichia coli K-12. II.
      Comparative study of hybrid and mutant forms of uridine phosphorylases].
AB  - Genes for hybrid uridine phosphorylases (UPases) consisting of fragments of amino
      acid sequences of UPases from Escherichia coli and Salmonella typhimurium were
      constructed. Producing strains of the corresponding proteins were genetically
      engineered. Mutant forms of the E. coli K-12 UPase were produced by site-directed
      mutagenesis. A comparative study of the enzyme properties of the mutant and
      hybrid forms of bacterial UPases was performed. It was shown that Asp27 unlike
      Asp5 and Asp29 residues of the E. coli UPase forms part of the active site of the
      protein. A scheme of the involvement of Asp27 in the binding of inorganic
      phosphate is proposed.

PMID- 11443941
TI  - [Polymethylene derivatives of nucleic bases with omega-functional groups. II.
      Adenine and hypoxanthine derivatives].
AB  - N9-Polymethylene derivatives of adenine and hypoxanthine with various functional
      groups in the omega-position of the alkyl substituent were synthesized. Their
      physico-chemical properties and effect on the HIV reverse transcriptase and DNA
      topoisomerase I were studied.

PMID- 11443942
TI  - [Reagents for modification of protein-nucleic acids complexes. II. Site-specific
      photomodification of DNA-polymerase beta complexes with primers elongated by the
      dCTP exo-N-substituted arylazido derivatives].
AB  - Substrate properties of the earlier synthesized and characterized dCTP
      derivatives bearing in the exo-N-position of cytosine 2-(4-azido-2,3,5,6
      tetrafluorobenzoylamino)ethyl (I), 2-(2-nitro-5-azidobenzoylamino)ethyl (II), 2
      (4-azido-2,3,5,6-tetrafluorobenzylideneaminooxymethylcarbonylamino)ethyl (III), 4
      (4-azido-2,3,5,6-tetrafluorobenzylideneaminooxy)butyloxy (IV), or 4-(4-azido
      2,3,5,6-tetrafluorobenzylidenehydrazinocarbonyl)butyl- carbonylamino (V) groups
      were studied in the primer extension reaction catalyzed by rat DNA polymerase
      beta. Unlike the earlier results obtained with HIV reverse transcriptase, dCTP
      derivatives (I)-(III) were not recognized by rat DNA polymerase beta as dTTP
      analogues, and all the five nucleotides were utilized as dCTP analogues. When
      compared with dCTP, Km values for the synthesized dCTP derivatives were higher by
      a factor of 4-20; Vmax were 1-2.3 times higher for (I)-(III) and (V) but 20-fold
      lower for derivative (IV). Site-specific photomodifications of the primer
      template-DNA polymerase beta complexes were carried out using photoreactive
      reagents PRI-PRV, obtained in situ by extension of 5'-32P-labeled primers with
      dCTP analogues (I)-(V), respectively, when exposed to UV irradiation at 303-313
      nm. Reagents PRI and PRIV provided the maximum photocrosslinking of the 5'-32P
      labeled primer to the DNA template (56%) and to the enzyme (20%), respectively.
      The lowest efficiency of photocrosslinking was observed for PRII (about 1%).

PMID- 11443943
TI  - [Preparation of photoreactive oligonucleotide duplexes and their application for
      photoaffinity modification of DNA-binding proteins].
AB  - To introduce photoreactive dNTP residues to the 3'-end of a mononucleotide gap,
      base-substituted photoreactive deoxynucleoside triphosphate derivatives, (5-[N
      (2,3,5,6-tetrafluoro-4-azidobenzoyl)-trans-3-aminopropenyl-1]- and 5-(N-[N-(4
      azido-2,5-difluoro-3-chloropyridine-6-yl)-3-aminopropionyl]- trans-3
      aminopropenyl-1)-2'-deoxyuridine 5'-triphosphates, were used as substrates in the
      DNA polymerase beta-catalyzed reaction. The resulting nick, containing a modified
      base at the 3'-end, was sealed by T4 phage DNA ligase. This approach enables the
      preparation of DNA duplexes bearing photoreactive groups at predetermined
      position(s) of the nucleotide chain. Using the generated photoreactive DNA
      duplexes, the photoaffinity modifications of DNA polymerase beta and human
      replicative protein A (hRPA) were carried out. It was shown that DNA polymerase
      beta and hRPA subunits were modified with the photoreactive double-stranded DNA
      considerably less effectively than by the nicked DNA. In the case of double
      stranded DNA, the hRPA p70 subunit was preferentially labeled, implying a crucial
      role of this subunit in the protein-DNA interaction.

PMID- 11443944
TI  - [Synthesis of oligodeoxyribonucleotides containing oleylamine moieties].
AB  - A method for directional introduction of oleylamine residues to any position of
      oligodeoxyribonucleotides during their automated synthesis was developed. The
      presence of oleylamine residues in 3'- or 5'-terminal nucleotides was shown to
      have no effect on the thermodynamic stability of DNA duplexes formed by such
      oligonucleotides and the complementary sequences. The rate of the snake venom
      phosphodiesterase hydrolysis of oligonucleotides containing oleylamine residues
      in the 3'-terminal units was shown to be markedly lower than that of natural
      oligonucleotides.

PMID- 11443945
TI  - [Synthesis of 1-hydroxyalkyl-3-substituted ureas and thioureas as a substrates
      for alcohol dehydrogenase].
AB  - A series of 1-(2-hydroxyethyl)- and 1-(3-hydroxyethyl)-3-substituted ureas and
      thioureas were synthesized. 1-(3-Hydroxyethyl)-3-acylthioureas were shown to be
      specific substrates for alcohol dehydrogenase in vitro.

PMID- 11443946
TI  - [The weak neurotoxin from Naja kaouthia Cobra venom decreases the arterial blood
      pressure in rats].
AB  - The weak neurotoxin from the Naja kaouthia cobra venom was found to reduce, under
      the intravenous administration to rats, the arterial blood pressure and increase
      the heart rate.

PMID- 11443947
TI  - [Cobra venom contains a protein belongs to the CRISP family].
AB  - Amino acid sequences of several fragments of the 25 k protein (molecular mass
      24,953 Da) previously isolated from cobra Naja kaouthia (Kukhtina et al. Bioorg.
      Khim., 2000, vol. 26, pp. 803-807) were determined. Their comparison with the
      primary structures of known proteins showed that the 25 k protein belongs to the
      CRISP family and is the first protein of this type identified in cobra venoms.

PMID- 11443948
TI  - [Arachidonoylcholine and N,N-dimethylaminoethyl arachidonate are new cholinergic
      compounds].
AB  - Choline and N,N-dimethylaminoethyl esters of arachidonic and some other fatty
      acids were synthesized. Experiments on the embryos and larvae of sea urchins,
      sensitive to cholinergic compounds, showed that arachidonoylcholine exhibited
      cholinomimetic activity similar to that of nicotine whereas N,N
      dimethylaminoethyl arachidonate acted as an acetylcholine antagonist. The
      corresponding esters of docosahexaenoic acid displayed similar biological
      properties.

PMID- 11443949
TI  - [Nucleic acids and signal transduction. Symposium, July 26-29, 2000., Waltham,
      MA, USA].

PMID- 11443950
TI  - [RNA interference-- a novel mechanism of gene expression regulation and a novel
      method for study of their functions].

PMID- 11443951
TI  - A new economical method to remove humic substances in water: adsorption onto a
      recycled polymeric material with surfactant addition.
AB  - Cationic surfactants were used to enhance the adsorption of dissolved organic
      matter (DOM), contained in the effluent of municipal wastewater, onto
      polypropylene (PPL), a polymeric synthetic adsorbent made from recycled plastics.
      Both batch and continuous up-flow column experiments were carried out. The DOM,
      in the form of humic acid, was treated with a range of cationic surfactants,
      then, adsorption experiments were conducted to evaluate the adsorption of the
      mixture onto PPL in both its soluble and precipitated forms. This research
      validated the feasibility of the proposed system in which anionic humic acid is
      removed from the aqueous phase by forming neutral hydrophobic molecules with
      cationic surfactants and subsequently by adsorbing them on the hydrophobic
      surface of PPL.

PMID- 11443952
TI  - Impact of cold and dilute sewage on pre-fermentation--a case study.
AB  - The municipal sewage treatment plant (STP) of the city of Ghent (Belgium) has to
      be retrofitted to a 43%-increase in the nitrogen treatment capacity and to
      phosphorus removal. Cold weather, dilute sewage and a critical COD over N ratio
      make the retrofit a challenge for full biological nutrient removal. The potential
      for fermentation of primary sludge to alter those critical feed sewage
      characteristics was experimentally evaluated. The idea was that the pinpoint
      introduction of fermentate could optimise the available reactors by achieving
      high-rate denitrification and enhanced biological phosphorus removal. The
      fermentation process was evaluated with a bench scale apparatus. At 20 degrees C
      (heated process), the hydrolysis yield--expressed in terms of soluble COD--varied
      from 11% to 24% of the total sludge COD. The fermentation yield expressed in VFA
      COD varied from 8% to 13% of the total sludge COD. The efficiency of heated
      fermentation of primary sludge was lower during cold and wet weather, due to the
      different sewage characteristics, as a result of extended dilution periods and
      low temperature. The raw sewage, the primary effluent and the fermentate were
      fractionated according to the requirements for the IAWQ Activated Sludge Model
      No. 2d. The results clearly show that fermentation in the sewer played an
      important role and temperature was the driving parameter for the characteristics
      of the dissolved COD. Instead, the weather flow conditions were the driving
      parameter for the characteristics of the suspended COD. The results of the
      detailed fractionation were used as background for process evaluation. The final
      scenario choice for the retrofit depends on a cost-efficiency calculation.

PMID- 11443953
TI  - Experimental validation of a single-OUR method for wastewater RBCOD
      characterisation.
AB  - Wastewater characterisation is of primary importance for the correct design and
      management of a treatment plant. The aim of this work was the evaluation of a new
      rapid and easy to use respirometric technique for the characterisation of readily
      biodegradable COD (RBCOD). When the necessary calibration curve is obtained, the
      RBCOD assessment procedure needs less than 30 minutes. On the contrary,
      conventional techniques require some hours. The first step consists in
      calculating a calibration curve in order to point out the correlation between
      oxygen consumed and known amount of added Sodium Acetate. To a well aerated
      biomass (in order to remove residual readily biodegradable substrate) a known
      amount of Sodium Acetate is added and the related OUR is measured. The oxygen
      consumed (delta DO) is related to the added COD (as Sodium Acetate). Therefore,
      the RBCOD concentration in wastewater samples can be obtained according to the
      following steps: (1) measure delta DO; (2) multiply delta DO by the Volume of
      aerated mixed liquor used in the test; (3) from the calibration curve, calculate
      the readily biodegradable COD equivalent to Acetate; (4) estimate RBCOD
      concentration multiplying the wastewater sample volume tested in the reactor.
      Some advantages of this technique are described in the paper.

PMID- 11443954
TI  - Full-scale application of the SHARON process for treatment of rejection water of
      digested sludge dewatering.
AB  - At the Rotterdam Dokhaven WWTP the first full-scale application of the SHARON
      process has been constructed. In the SHARON process, rejection water from
      dewatering of digested sludge is treated for N-removal. It concerns a highly
      active process operating without sludge retention. The single tank reactor is
      intermittently aerated. Due to differences in growth rate nitrite oxidisers are
      washed out of the system while ammonia oxidisers can be maintained, resulting in
      N-removal over nitrite. The SHARON process has been selected after comparison
      with several other techniques. The feed of the SHARON tank is concentrated, with
      ammonia concentrations over 1 g N/l. The first results show that conversion rates
      of 90% are quite possible with N-removal mainly via the nitrite route. The
      process was shown to be stable. Due to the high inlet concentrations pH control
      is of great importance, preventing process inhibitions. The acidifying effect of
      nitrification can be compensated completely by CO2 stripping during aeration and
      by denitrification. Heat production by biological conversions appeared to be
      significant, due to the high inlet concentrations, and contributes to the optimal
      operating temperature of 30-40 degrees C.

PMID- 11443955
TI  - Prediction of full-scale dewatering results of sewage sludges by the physical
      water distribution.
AB  - The dewaterability of sewage sludge can be described by the total solids
      concentration of the sludge cake and the polymer-demand for conditioning. The
      total solids concentration of the sludge cake depends on the physical water
      distribution. The various types of water in sewage sludge are mainly
      distinguished by the type and the intensity of their physical bonding to the
      solids. In a sewage sludge suspension four different types of water can be
      distinguished. These are the free water, which is not bound to the particles, the
      interstitial water, which is bound by capillary forces between the sludge flocs,
      the surface water, which is bound by adhesive forces and intracellular water.
      Only the share of free water can be separated during mechanical dewatering. It
      can be shown, that by thermo-gravimeteric measurement of the free water content,
      an exact prediction of full-scale dewatering results is possible. By separation
      of all free water during centrifugation the maximum dewatering result is reached.
      Polymer conditioning increases the velocity of the sludge water release, but the
      free water content is not influenced by this process. Furthermore it is not
      possible, to replace the measuring of the water distribution by other individual
      parameters such as ignition loss.

PMID- 11443956
TI  - Transfer number in fine bubble diffused aeration systems.
AB  - On the basis of full-scale data from 58 clean water tests performed in 26
      activated sludge tanks equipped with fine bubble diffusers and of a theoretical
      approach, it can be stated that fine bubble aeration systems with total floor
      coverage arrangement provide higher kLa values and the lowest spiral liquid
      circulation. An efficiency criterion for oxygen transfer (NT) was defined on the
      basis of the dimensional analysis. The transfer number NT allows us to take
      account of the impact of vertical liquid circulation movements on oxygen
      transfer. The values of NT calculated from the results of full scale nonsteady
      state clean water tests vary from 5.3 x 10(-5) to 9.1 x 10(-5) and are directly
      dependent upon the arrangement of air diffusers. It has been shown that the
      highest transfer numbers corresponded to the total floor coverage arrangement and
      the average calculated NT values is 7.7 x 10(-5), independently of the diffuser
      density and of the gas velocity, over the ranges studied. The lowest transfer
      numbers are obtained when the diffusers are located in separate grids, and the
      transfer number is reduced with increasing air flow rate.

PMID- 11443957
TI  - Kinetic start-up performance of two large treatment plants for nutrient removal.
AB  - In 1987 an action plan was passed in the Danish Parliament demanding a
      considerable reduction of the discharge of nutrients to the aquatic environment
      in Denmark. Consequently, the two largest wastewater treatment plants in the
      Copenhagen area had to be upgraded to include nutrient removal. For more than 8
      years an extensive effort has been made to determine an optimum solution for this
      upgrading from a technical and financial point of view. The work included six
      years of comprehensive pilot plant investigations with the aim of thoroughly
      studying and interpreting the kinetics of the processes involved. The
      investigations revealed valuable information particularly concerning limitations
      of the nitrification process. Consequently, the investigations contributed to an
      expectation of no unforeseen problems during the implementation of the upgraded
      plants. This paper presents the results of the start-up of the two full-scale
      plants with the main emphasis laid on the kinetic performance in relation to the
      information achieved from the pilot tests. The results showed that the start-up
      of the full scale plants proceeded with great accuracy as expected from the
      investigations. Accordingly, the implementation of the plants was carried out
      successfully, ending an era of more than 10 years in total.

PMID- 11443958
TI  - A modification to the Activated Sludge Model No. 2 based on the competition
      between phosphorus-accumulating organisms and glycogen-accumulating organisms.
AB  - A modification to the ASM2 is proposed which permits representation of the
      competition between phosphorus accumulating organisms (PAOs) and glycogen
      accumulating organisms (GAOs) in a nutrient removal activated sludge system. Some
      important aspects, which are not considered in ASM2, are discussed. The proposed
      modification includes denitrification by PAOs, PAO glycogen storage capability
      and GAO metabolism model. It is shown that the proposed modification is capable
      of describing pilot plant data using a single set of stoichiometric and kinetic
      parameters over three different sludge ages (16, 14 and 12 days). The modified
      ASM2 may be applicable to a wide range of situations where PAOs and GAOs can
      compete. This modification may well provide a better understanding about GAO
      behaviour.

PMID- 11443959
TI  - Polyvinyl alcohol as an immobilization matrix--a case of gold biosorption.
AB  - The use of polyvinyl alcohol (PVA) as a matrix for cell immobilization has been
      extensively studied in various biological systems. However, its suitability has
      not been reported in biosorption studies where inactivated cells are used as
      biosorbents. In this work, PVA and alginate as immobilization matrices (for the
      biosorption of gold by a fungal biomass) were investigated by examining their
      physical and chemical properties. Compared to alginate gels, PVA gels were shown
      to be more resistant to mechanical abrasion, and more stable over a wide pH
      range. Although the PVA matrix did not affect the equilibrium uptake in gold
      biosorption studies, the time required to attain a removal of 80% of the initial
      metal concentration was 1.7 times that of the freely suspended biosorbent. This
      contrasts with the alginate immobilized biosorbent which required an increase of
      well over ten times the duration to attain the same removal efficiency. Results
      indicated that PVA gels conferred a lower mass transfer resistance than alginate
      gels. Gold biosorption by the PVA-immobilized fungi followed the commonly used
      Langmuir and Freundlich adsorption isotherm models although the former gave a
      better fit. The uptake of gold was dependent on the initial gold concentration
      and the biomass loading. Using a fungal biosorbent and gold ions as the model
      system, the results demonstrate the potential in the use of the PVA as a cell
      immobilisation matrix for biosorption studies.

PMID- 11443960
TI  - Numerical modelling of dynamic sludge blanket behaviour in secondary clarifiers.
AB  - New developments in numerical modelling of turbulent and density-affected flow in
      secondary clarifiers are reported. The sludge blanket is included in the
      computation domain which allows us to account for sedimentation and resuspension
      of sludge as well as the growth and diminution of the sludge blanket and at the
      same time respecting mass conservation. It is shown how strongly the prediction
      of the sludge-blanket height depends on the approaches to describe the settling
      behaviour of the sludge and the rheological properties within the sludge blanket.
      Further, an example of dynamic simulation is presented and discussed. This
      demonstrates how the sludge blanket behaves during load variation and that
      instabilities may occur at the interface of sludge blanket and supernatant,
      potentially resulting in sludge wash-off during transient phases, which is not
      only during load increase but also during load decrease.

PMID- 11443961
TI  - UV dose distribution characterization using fractal concepts for system
      performance evaluation.
AB  - This paper presents a mathematical model for estimating the UV dose distribution
      delivered by continuous-flow UV disinfection processes. The model adopts fractal
      concepts and a stochastic method to simulate microorganism (particle)
      trajectories through the irradiation zone of an open-channel UV system. The
      irregularity of particle trajectories attributable to random movements was
      characterized by fractal dimension. In turn, trajectory-specific doses were
      calculated by integrating UV intensity over travel time. Results of these
      simulations indicated that radiation intensities along the trajectories could be
      highly variable. Therefore, microorganisms are expected to receive a broad range
      of radiation doses as a result of variations in radiation intensity along their
      trajectories and spatial heterogeneity in the radiation intensity field. This
      supports previous assertions that the conventional averaged-dose approach will
      result in substantial deviations between predicted and actual system performance.
      Implications of the results in terms of treatment efficiency and system design
      are discussed. The presented approach is found to be useful as a tool for rapid
      estimation of the dose distribution delivered by UV processes.

PMID- 11443962
TI  - Improving the efficiency of a wastewater treatment plant by fuzzy control and
      neural network.
AB  - One of the main problems in operating a wastewater treatment plant is the
      purification of the excess water from dewatering and pressing of sludge. Because
      of a high load of organic material and of nitrogen it has to be buffered and
      treated together with the inflowing wastewater. Different control strategies are
      discussed. A combination of neural network for predicting outflow values one hour
      in advance and fuzzy controller for dosing the sludge water are presented. This
      design allows the construction of a highly non-linear predictive controller
      adapted to the behaviour of the controlled system with a relatively simple and
      easy to optimise fuzzy controller. Measurement results of its operation on a
      municipal wastewater treatment plant of 60,000 inhabitant equivalents are
      presented and discussed. In several months of operation the system has proved
      very reliable and robust tool for improving the system's efficiency.

PMID- 11443963
TI  - Experimental considerations on monitoring ORP, pH, conductivity and dissolved
      oxygen in nitrogen and phosphorus biological removal processes.
AB  - An experimental study on monitoring Oxidation Reduction Potential (ORP), pH,
      Conductivity and Dissolved Oxygen (DO) in an Enhanced Biological Nutrient Removal
      process has been carried out. In the anaerobic phase, while ORP and conductivity
      were not reliable in monitoring simultaneously denitrification and P-release, pH
      showed the best performances. A significant relationship between P-released and
      pH variation was found. During the aerobic phase both ORP and pH were able to
      monitor successfully the nitrification, even though pH was much more reliable. pH
      can be also used for monitoring and control enhanced P-uptake. It has been
      concluded that, for a reliable and effective control of biological N and P
      removal processes a more sophisticated control system seems to be necessary.

PMID- 11443964
TI  - State estimation for a biological phosphorus removal process using an asymptotic
      observer.
AB  - This study investigated the use of an asymptotic observer for state estimation in
      a continuous biological phosphorus removal process. The estimated states are the
      concentration of heterotrophic, autotrophic and phosphorus accumulating
      organisms, polyphosphate, glycogen and PHA. The reaction scheme describing the
      process was simplified from a combined ASM 1-Delft model. Three examples were
      investigated: operation at steady state, operation at steady state with a random
      white-noise in the measurements and operation with a ramp disturbance. In each
      case, the estimation was quite accurate even if the convergence, driven by the
      dilution rate, was slow (from 15 to 60 days). The propagation of the measurement
      noise and a bias in the estimation of glycogen and PHA could be the result of the
      high condition number of one of the matrices used in the algorithm of the
      asymptotic observer for the aerated tanks.

PMID- 11443965
TI  - Provision of data for on-line simulation.
AB  - A crucial factor for the quality and results of the on-line simulation of a
      municipal sewage treatment system is the provision of the requisite data in
      adequate quality and density. Since the measured data cannot be incorporated in a
      simulation model without prior processing, it should be prepared in such a way
      that it can be converted to the model-related input quantities. If individual
      input measuring signals fail, substitute value concepts must be developed which
      are based on the remaining information. With this it is possible to ensure the
      continuous provision of data. Various approaches are possible in seeking a
      solution to this problem. At the Wupperverband a detailed programme of
      investigation on the subject area of the processing of inflow data is being
      implemented as a component of future on-line simulation at Wuppertal-Buchenhofen
      STP.

PMID- 11443966
TI  - A scientific approach to wastewater recovery and reuse in the textile industry.
AB  - Wastewater recovery and reuse in industries requires all the basic steps of
      quality management. It should involve a comprehensive in plant survey of
      processes with wastewater generation, identification of recoverable streams, and
      treatment requirements for reuse. It should equally undertake evaluation of
      wastewater quality remaining after segregation of the recovered portion, with
      specific emphasis on technological implications of appropriate treatment and
      compliance with effluent limitations. In this study, all these factors were
      experimentally assessed and evaluated for a knit fabric processing textile plant.

PMID- 11443967
TI  - Application of membrane and ozonation technologies to remove color from agro
      industry effluents.
AB  - The results of membrane and ozonation experiments carried out on various agro
      industry effluents including fermentation (baker's yeast), corrugated board,
      opium alkaloid and textile dying industries are presented. The experiments were
      performed using lab-scale membrane and ozonation reactors. Color removals were in
      the range of 80 to 99% for the membrane treatment studies. Ozonation experiments
      have shown that color removals in the range of 83 to 98% are possible for the
      investigated wastewaters. Final color levels were lower than 100 Pt-Co unit,
      which is quite acceptable aesthetically. The relative unit treatment costs of
      ozonation were about two times higher than membrane systems especially for very
      strong colored effluents including fermentation and opium alkaloid industries.
      The study has demonstrated that both membrane and ozonation technologies are
      viable options for color removal.

PMID- 11443968
TI  - Abattoir effluent treatment and protein production.
AB  - A modified SBR process was evaluated for biological pretreatment of abattoir
      effluent. One of the main objectives was to produce a biomass with low SVI that
      can be used as a protein feed addition for animals. A pilot plant was used with
      reactor working volume of 60 kl. The process was easy to operate and adapted
      readily to changes in raw effluent generation. COD removal was in excess of 85%.
      A biomass was produced with SVI lower than 80 ml/g that included aerobic granular
      sludge. Filamentous organism growth could be limited by controlling the dissolved
      oxygen concentration in the reactor. Crude protein values of 27 to 37% were
      obtained. The optimum cell residence time to maximise protein production was
      between 4 and 5 days. The process can be described as a protein recovery and
      production process.

PMID- 11443969
TI  - Nitrate and pesticide removal by a combined bioelectrochemical/adsorption
      process.
AB  - Biological denitrification and trace pesticide removal in a combined biofilm
      electrode reactor/adsorption process has been investigated. In long-term (more
      than 260 days) continuous experiments, influent and effluent concentrations of
      nitrate, nitrite, isoprothiolane and gas composition were measured at different
      electric current and pesticide loading conditions. Experimental results showed
      that complete and stable denitrification was achieved in BER without accumulation
      of nitrite and nitrous oxide. Isoprothiolane (IPT) was removed by adsorption onto
      either granular activated carbon or silicone resin. Removal efficiency of IPT
      exceeding 97% was achieved and effluent concentration was below the guideline
      value (40 micrograms/l). Theoretically predicted effluent concentrations were in
      good agreement with the observed results. From these results, it is concluded
      that the combined process is applicable to treat nitrate and pesticide
      contaminated drinking water. Moreover, from comparison with former studies,
      different possible options to further enhance the decomposition of pesticide were
      suggested.

PMID- 11443970
TI  - Full-scale evaluation of heat balance for autothermal thermophilic aerobic
      treatment of food processing wastewater.
AB  - A full-scale autothermal thermophilic aerobic treatment (ATAT) of food-processing
      wastewater was evaluated in this study. The wastewater was rich in oil and grease
      at concentrations of 1,500-2,000 mg/L. The system has been operated for more than
      one and a half years since the startup. Under steady state conditions, the ATAT
      process was capable of spontaneous reaction at temperatures of 45-55 degrees C
      without the addition of external heat. Treatment efficiency was as high as 95% in
      COD reduction at a volumetric COD loading of 4.1 kg/m3-d. A mathematical heat
      balance model was developed based on the theoretical considerations of heat
      sources and losses for the ATAT process. A computer algorithm was established to
      evaluate specific heat potential (Hs) of the wastewater under steady state
      conditions. Six months of steady-state data were used for the evaluation. The
      result shows that on average the wastewater had a specific heat potential (Hs) of
      4,720 kcal/kg-COD removed and the biological heat contributed 41.4% of the total
      heat input. A net heat flux of 4,270 kcal/min and volumetric heat intensity (Hv)
      of 38.0 kcal/L was necessary to maintain reaction temperature at 48.2 degrees C
      for the ATAT process. The full-scale ATAT process showed the typical
      characteristics of high removal rate, low sludge yield, and poor solids
      settleability for thermophilic aerobic treatment reported in the literature.

PMID- 11443971
TI  - Struvite precipitation potential for nutrient recovery from anaerobically treated
      wastes.
AB  - Geochemical equilibrium speciation modeling was used to determine optimum
      conditions for precipitation of magnesium ammonium phosphate, or struvite, for
      the recovery of nutrients from anaerobically digested wastes. Despite a wide
      range of pH values with the potential to precipitate struvite, the optimum pH was
      determined to be 9.0. Bench experiments conducted on effluent from an anaerobic
      sequencing batch reactor (ASBR) treating swine wastes achieved a maximum of 88%
      ammonia removal at a pH of 9.5 with added magnesium and phosphate to achieve an
      ammonium: magnesium: phosphate molar ratio of 1:1.25:1. Struvite precipitation
      was performed on a continuous basis in a pilot-scale ASBR treating swine wastes.
      Through the addition of supplemental magnesium and phosphate, the ammonia
      concentration was reduced from 1500 mg/L as nitrogen to less than 10 mg/L. The
      supenatant from the struvite precipitation clarifier was recycled to the feed of
      the ASBR without adverse impact, simulating on-farm effluent reuse as flush
      water.

PMID- 11443972
TI  - Inhibition by chromium and cadmium of anaerobic acidogenesis.
AB  - The effects of chromium (III) and cadmium on the anaerobic acidogenesis of a
      simulated dairy waste were examined using serum vials. At Cd dosages less than 20
      mg/l, the acidogenesis process was enhanced by the dosage, resulting in a higher
      degree of acidification, protein conversion, and hydrogen production than the
      control. At dosages over 20-mg/l, Cd inhibited the acidogenesis. The Cr (III)
      dosage of 5 mg/l reduced overall volatile fatty acid and alcohol generation,
      degree of acidification, conversions of lactose, lipid and protein, and total
      biogas production, with the exception of accumulation of hydrogen and propionate.
      At dosages exceeding 5 mg/l, Cr (III) had a severe inhibition on the
      acidogenesis. The Cd concentrations which caused a 50% reduction in total
      volatile fatty acid and alcohol production, degree of acidification and
      cumulative gas production were higher than the corresponding values caused by Cr
      (III), suggesting that Cr (III) was more toxic to acidogenic bacteria than Cd.

PMID- 11443973
TI  - Enhancement of anaerobic treatability of olive oil mill effluents by addition of
      Ca(OH)2 and bentonite without intermediate solid/liquid separation.
AB  - Previous work on the anaerobic treatment of olive oil mill effluents (OME) have
      shown: (a) lipids, even if more easily degraded than phenols, were potentially
      capable of inhibiting methanogenesis more strongly; (b) a pretreatment based on
      addition of Ca(OH)2 and bentonite removed lipids almost quantitatively; (c)
      preliminary biotreatability tests performed on the pretreated OME showed high
      bioconversion into methane at very low dilutions ratios, especially when the
      mixture (OME, Ca(OH)2 and bentonite) was fed to the biological treatment without
      providing an intermediate phase separation. This paper was directed towards two
      main aims: (a) to optimize pretreatment: the best results in terms of methane
      production were obtained by addition of Ca(OH)2 up to pH 6.5 and of 10 g L-1 of
      bentonite; (b) to evaluate the enhancement of anaerobic treatability of OME
      pretreated under optimized conditions in a lab-scale continuous methanogenic
      reactor fed with the substrate without intermediate solid/liquid separation: very
      satisfactory performances were obtained (at an organic load of 8.2 kg COD m-3 d-1
      and at a dilution ratio of 1:1.5 total COD removal was 91%, biogas production was
      0.80 g CH4 (as COD)/g tot. COD, lipids removal was 98%, phenols removal was 63%).
      The results confirm the double role played by bentonite (adsorption of the
      inhibiting substances and release of the adsorbed biodegradable matter in the
      methanogenic reactor).

PMID- 11443974
TI  - Marine-based waste stabilisation ponds: an evaluation of the hydraulic viability.
AB  - Marine-Based Waste Stabilisation Ponds, formed by floating boom/skirt curtain
      enclosures anchored in sheltered waters, have recently been proposed for
      provision of low-cost effluent treatment facilities where land availability is
      limited in rapidly expanding coastal cities in the Third World. This paper
      outlines findings from a viability assessment, which drew on a preliminary site
      evaluation and baseline environmental survey (for a site in sheltered waters in
      the Far East), laboratory studies involving scale model tests in
      wave/wind/current flumes, and a structural and design loading study. It focuses
      on hydraulic and hydrodynamic considerations and reports the study's conclusions.

PMID- 11443975
TI  - Duckweed based wastewater treatment (DWWT): design guidelines for hot climates.
AB  - Conventional wastewater treatment systems are expensive in either investment or
      running costs. On the other hand, waste stabilisation ponds may be unable to meet
      effluent standards for nutrients. Wastewater treatment using duckweed therefore
      becomes more significant as an option capable of achieving effluent standards and
      generating revenue from selling the duckweed. However existing duckweed based
      wastewater treatment (DWWT) systems have high land requirements despite being
      able to reduce concentrations of organic compounds and pathogens to acceptable
      levels. Improved guidelines for the design of DWWT are necessary to obtain a
      reliable and cost-effective wastewater treatment plant using duckweed. This
      guideline provides a DWWT design program using spreadsheets for different
      configurations of wastewater treatment units using duckweed. The design program
      developed suggests that a combination of anaerobic ponds, DWWT systems and
      maturation ponds can minimise land requirements and capital costs while achieving
      specified effluent standards. In order to achieve effluent standards, the land
      required is typically from 1.5 to 1.8 m2/capita (excluding associated
      facilities), capital costs are in the range from 7.9 to 9.7 USD/capita, with a
      retention time from 15 to 18 days. Income generation is dependent mainly on the
      social and cultural acceptability of duckweed use within the community.

PMID- 11443976
TI  - Comparison of operational design criteria for subsurface flow constructed
      wetlands for wastewater treatment.
AB  - Many communities are investigating the use of constructed wetlands as a simple,
      viable alternative to poorly operating on-site wastewater treatment. Currently,
      the most popular design models in the U.S.A. for subsurface flow units are the US
      Environmental Protection Agency (EPA) and the Tennessee Valley Authority (TVA)
      methods. However, there has been limited data verifying if the operating
      performance is up to design standards. In order to address this problem, this
      paper documents the performance of such treatment systems over a broad range of
      conditions in North Alabama. The operational data is used to determine a best-fit
      value of reaction rate constant and proposes improved input parameters for both
      design models. According to this data, the average plug-flow reaction rate
      constant was calculated to be 0.70 d-1 for the EPA method, while the recommended
      organic loading criterion is 11.4 m2/kg BOD5 per day into the wetland for the TVA
      method.

PMID- 11443977
TI  - Control measures for wastewater treatment plants during storm flow.
AB  - In the context of the development of treatment plant control techniques, three
      measures for maintaining a high efficiency of treatment plants during rainfall
      events were tested. The three measures are increasing the nitrification volume by
      operating a facultative aeration, bypassing the primary sedimentation and adding
      flocculants before secondary sedimentation. Ammonia concentrations and ammonia
      loads were used in combination with rainfall forecasts as the criteria for
      putting the measures into operation. A simulation based on the Activated Sludge
      Model No. 1 and a pilot scale plant were used for testing the measures. The
      results show that all three measures may be suitable to cope with peak loads of
      treatment plants during rainfall events.

PMID- 11443978
TI  - Control and separation of algae particles from WSP effluent by using floating
      aquatic plant root mats.
AB  - In this paper, the potential uses of water hyacinth and its root mats for
      separating algae particles in the effluent from waste stabilization ponds (WSPs)
      were discussed. Pilot-scale integrated processes consisting of WSPs and multiple
      WHPs (water hyacinth ponds) were operated in order to extract effects of the root
      mats on the reduction of algae concentrations. Root mats in the bottom of WHPs
      separated significant amount of the algae cells through attachment as the
      effluent from WSPs passed through them. Attachment of the algae particles to the
      surface of live roots was found to be similar to adsorption phenomena but it
      lasted even at saturation, probably due to the continuous reproduction of active
      attachment sites by detachment and growth of the roots. Additionally, this paper
      discusses attachment mechanisms and other issues concerning design and polishing
      of the WSPs effluent by WHPs.

PMID- 11443979
TI  - Performance evaluation of a UASB--activated sludge system treating municipal
      wastewater.
AB  - Recent research has indicated the advantages of combining anaerobic and aerobic
      processes for the treatment of municipal wastewater, especially for warm-climate
      countries. Although this configuration is seen as an economical alternative, is
      has not been investigated in sufficient detail on a worldwide basis. This work
      presents the results of the monitoring of a pilot-scale plant comprising of an
      UASB reactor followed by an activated sludge system, treating actual municipal
      wastewater from a large city in Brazil. The plant was intensively monitored and
      operated for 261 days, divided into five different phases, working with constant
      and variable inflows. The plant showed good COD removal, with efficiencies
      ranging from 69% to 84% for the UASB reactor, from 43% to 58% for the activated
      sludge system only and from 85% to 93% for the overall system. The final effluent
      suspended solids concentration was very low, with averages ranging from 13 to 18
      mg/l in the typical phases of the research. Based on the very good overall
      performance of the system, it is believed that it is a better alternative for
      warm-climate countries than the conventional activated sludge system, especially
      considering the total low hydraulic detention time (4.0 h UASB; 2.8 h aerobic
      reactor; 1.1 h final clarifier), the savings in energy consumption, the absence
      of primary sludge and the possibility of thickening and digesting the aerobic
      excess sludge in the UASB reactor itself.

PMID- 11443980
TI  - Wastewater collection and treatment technologies for semi-urban areas of India: a
      case study.
AB  - Sanitation and wastewater management problems in small and medium towns in India
      (referred to as "semi-urban areas"--SUAs) are distinctly different from those of
      large cities or rural villages. There is an apparent lack of choices of
      appropriate sanitation options for these semi-urban areas, leading them to adopt
      on-site sanitation technologies. A field study of four such small towns in India
      was conducted to evaluate the suitability of available low-cost wastewater
      collection and treatment technologies, in light of their current practice. Based
      on the field study, this paper suggests a system comprising "combined surface
      sewers" and "reed-bed channel" for collection and treatment of wastewater for
      semi-urban areas, that can utilize all the existing infrastructure to effect
      better sanitation at lower costs. The suggested system involves converting the
      existing open wastewater collection drains on the road sides, as "decentralized"
      networks of covered drains with simple structural modifications to collect both
      wastewater and stormwater; and, converting the large open drains on the outskirts
      of SUAs that carry wastewater to agricultural fields, as gravel media filled beds
      planted with local reeds. Cost estimates for the towns studied indicate this
      system to be over 70% cheaper compared to conventional collection and treatment
      systems.

PMID- 11443981
TI  - Moving-bed biological treatment (MBBT) of municipal wastewater: denitrification.
AB  - Denitrification in a full-scale installation and a pilot plant for moving-bed
      biological treatment (MBBT) was subject to detailed investigation. Two different
      types of carriers were used in conventional activated sludge reactors: foam cubes
      and plastic tubes (Kaldnes). Both investigated carriers showed the same behavior
      with regard to denitrification capacity, temperature dependency and maximum COD
      and nitrate turnover. In contrast to the plastic tubes (Kaldnes), the sponge
      cubes stored remarkable amounts of substrate. The maximum denitrification rate
      with acetate as a substrate was 420 gNm-3d-1 at 10 degrees C and 730 gNm-3d-1 at
      20 degrees C. An average denitrification rate of 240 gNm-3d-1 (10 degrees C) was
      achieved with wastewater. A maximum of 37% of the COD in the influent was
      denitrified with a volumetric loading rate in the anoxic zone of 2.2 kgCODm-3d-1.

PMID- 11443982
TI  - Constructed wetland technology transfer to Nepal.
AB  - Constructed Wetland (CW) technology is still not wide spread in developing
      countries despite having great potential. This paper describes an approach
      carried out in Nepal to transfer CW technology for wastewater treatment. Three
      CWs (hospital wastewater treatment--20 m3/d, greywater treatment of a single
      household, septage treatment--40 m3/d) were built and two have been investigated
      so far. All systems are subsurface flow systems with at least one vertical flow
      stage. Their treatment efficiency turned out to be very high. Median load
      elimination rates of the hospital wastewater and greywater treatment plants were
      for TSS: 97 to 99%; BOD5: 97 to 99%; COD: 94 to 97%; NH4-N 80 to 99%; PO4-P: 5 to
      69%; Total Coliforms: 99.87 to 99.999% (3-5 log steps). Beside the treatment task
      the plants play an important role as demonstration sites to make common people
      and especially decision makers aware of the existing environmental problems and
      one possible solution. Several recommendations are pointed out to promote the
      technology in developing countries.

PMID- 11443983
TI  - Polyurethane foam based biofilter media for toluene removal.
AB  - Polyurethane foam medium was manufactured and analyzed to determine its
      suitability as a solid support medium for use in gas-phase biofilters. Physical
      and chemical studies were conducted to determine the medium's characteristics.
      The medium's ability to support an active biofilm capable of degrading volatile
      organic compounds was assessed using a laboratory scale biofilter fed a model
      waste stream containing toluene for more than 250 days with empty bed residence
      times (EBRTs) ranging from two to four minutes. Results are presented that show
      how a polyurethane foam medium with high porosity, suitable pore size, low
      density, and an ability to sorb water was able to remove over 99% of the influent
      toluene when fed at a concentration of 200 ppm. An operating strategy is
      described which effectively prevented two problems common to conventionally
      operated biofilter systems: nutrient limitations and biosolid accumulation.

PMID- 11443984
TI  - Field observations of dilution on the Ipanema Beach outfall.
AB  - Field observations of the Ipanema Beach, Rio de Janeiro, ocean sewage outfall are
      presented. Measurements of dilution and other wastefield characteristics were
      obtained by adding dye tracer to the effluent and measuring in-situ. Simultaneous
      measurements of oceanographic conditions were made by Acoustic Doppler Current
      Profilers, thermistor strings, and profiling instruments. Four experiments were
      performed, two during unstratified conditions when the plume was surfacing, and
      two during conditions of strong stratification when the plume was submerged. The
      minimum dilution varied from 30 to 130. The measurements reflect the worst case
      conditions as the campaigns were all made for weak currents.

PMID- 11443985
TI  - Effect of solids retention time on the performance and biological characteristics
      of a membrane bioreactor.
AB  - The purpose of this study was to compare the performance of a pilot-scale
      membrane bioreactor (MBR) in the treatment of municipal strength wastewater at
      solid retention times (SRTs) ranging from 30 days to two days. Cumulative
      nitrogen and phosphorus mass balances resulted in closures exceeding 90% at each
      steady state period. Biomass production rate and biomass viability generally
      increased with decreasing SRT, whereas overall enzymatic activity did not change
      significantly at most SRTs, but was highest at the two day SRT. Nitrification
      decreased at two day SRT but did not fail completely. At higher SRTs,
      nitrification was not noticeably affected by the sludge age. Phospholipid fatty
      acid (PLFA) analysis showed substantially diverse biomass in the sludge at
      different SRTs. Different ratios of gram positive bacteria, eukaryotic organisms,
      and yeast cells were observed in the mixed liquor at varying SRTs. On the other
      hand, BIOLOG analysis indicated that the overall capacity of the biomass to
      degrade different carbon substrates did not change significantly at different
      SRTs. The concentration of metals in the MBR mixed liquor declined steadily with
      decreasing SRT. The MBR effluent contained negligible amounts of Fe, Zn, Mn, and
      Co at each condition, indicating the retention of these metals regardless of the
      SRT.

PMID- 11443986
TI  - Aerobic treatment of inhibitory wastewater using a high-pressure bioreactor with
      membrane separation.
AB  - Wastewater high in phenolic content (948 mg/l) and dissolved solids (5.4 g/l) had
      to be treated to remove most of the organic material and toxic compounds. A
      laboratory scale High Pressure (3 bar) Bioreactor (HPB) was developed and
      operated to treat the wastewater using a ceramic ultra filtration membrane as
      biomass separator. The performance of the system was compared to a normal
      activated sludge plant (ASP) using sludge settling for separation. The HPB was
      more stable than the ASP, which twice became unstable with a resulting biomass
      loss. Both reactors removed 90% of the chemical oxygen demand (COD) loading,
      reducing the phenol concentration below 20 mg/l. The maximum COD removal rate of
      the HPB was 28 kg/m3.d compared to 15 kg/m3.d of the ASP, while the HPB achieved
      16-32 times better oxygen transfer than the ASP. It was concluded that the HPB
      was the preferred treatment system compared to the ASP, when treating high
      strength inhibitory wastewaters, due to its stable operating performance and high
      COD removal rate.

PMID- 11443987
TI  - Potential and limitations of alum or zeolite addition to improve the performance
      of a submerged membrane bioreactor.
AB  - In this study, alum and natural zeolite were added to a submerged membrane
      bioreactor (MBR) not only to reduce membrane fouling but also to increase the
      removal of nitrogen and phosphorus. Alum addition reduced significantly the
      rising rate of suction pressure and also resulted in stable and better COD
      removal. Although phosphorus removal was more than 90% by chemical precipitation,
      nitrification inhibition was observed. With the addition of natural zeolite,
      membrane permeability was greatly enhanced by the formation of rigid floc that
      had lower specific resistance than that of the control activated sludge floc. In
      particular, the nitrification efficiency was over 95% even at N-shock loading due
      to the ion-exchange capacity of zeolite. The mechanisms for improved membrane
      permeability through alum or zeolite addition were discussed in detail.

PMID- 11443988
TI  - Evaluation of refractory organic removal in combined biological powdered
      activated carbon--microfiltration for advanced wastewater treatment.
AB  - Biological powdered activated carbon (BPAC) was incorporated with a
      microfiltration (MF, 0.2 micron pore size) system to remove the refractory
      organic matter contained in secondary sewage effluent. A synthetic secondary
      sewage effluent was used as influent in this study, containing both non
      biodegradable organic substances (such as humic acid, lignin sulfonate, tannic
      acid and arabic gum powder) and biodegradable ones. These refractory organic
      materials were possibly degraded in contact with microorganisms for 20-27 days.
      Although humic acid and arabic gum were weakly adsorbed on the activated carbon,
      they could be effectively removed in the BPAC reactor. The TOC removal at a
      powdered activated carbon (PAC) concentration of 20 g/L was higher than at 0.5-2
      g PAC/L (83% and 66-68%, respectively). The higher removal efficiency was due to
      the increased rejection at the membrane module in which most of the PAC was
      accumulated. More than 90% of non-biodegradable compounds removal (detected as
      E280, UV absorption at 280 nm) occurred in the BPAC reactor. The biological
      growth parameter b/Y, used in system design, was estimated to be 0.017 d-1.
      Relatively high permeate flux of 1.88 m/d could be obtained even at higher PAC
      concentration of 20 g/L.

PMID- 11443989
TI  - Activated sludge flocculation: direct determination of the effect of calcium
      ions.
AB  - The effect of calcium on activated sludge flocculation dynamics is investigated
      using a unique experimental technique. The technique allows on-line analysis of
      the size of activated sludge flocs during flocculation and provides valuable
      insight into the mechanisms of flocculation. Activated sludge samples were
      firstly sonicated for 3 minutes at 50 W and then stirred at 100 rpm. The floc
      size was subsequently measured on-line using a Malvern Mastersizer/E. For
      concentrations of calcium less than 4 meq/L no significant increase in final floc
      size was observed even though an increase in the initial rate of change of floc
      size could be seen. Addition of calcium greater than 4 meq/L resulted in a
      dramatic increase in floc size. Results from this investigation support the
      theory that cations are involved in flocculation through cationic bridging, and
      will be used in ongoing investigations to model the flocculation process.

PMID- 11443990
TI  - Flotation with polyelectrolytes as a first step of a more sustainable wastewater
      treatment system.
AB  - Within the framework of a research programme into more sustainable wastewater
      treatment systems based on physical-chemical pretreatment the application of
      dissolved air flotation (DAF) with polyelectrolytes as a primary treatment was
      investigated. Experiments with municipal wastewater were carried out in 2.5 I
      flotation batches and in a 100 I DAF pilot reactor. Two cationic polyelectrolytes
      (PEs) with molecular weights of 4 x 10(6) g/mol and 8 x 10(6) g/mol, were tested.
      The higher weight PE was more effective in removing turbidity and was used in the
      pilot experiments for coagulation/flocculation. Within the pilot system
      experiments the dry solids concentration of the float layer as well as the
      removal efficiencies of turbidity, CODparticulate, CODdissolved and nutrients,
      were studied. Typical results were that the obtained dry solids concentration of
      the floated sludge was 10%, when the float layer was removed after several hours.
      By using polyelectrolytes it was possible to remove more than 80% of
      CODparticulate and turbidity at dosages of 7-8 mg/g influent COD (i.e. 5 mg
      PE/100 NTU). The removal efficiency of CODdissolved was low. There was a
      proportional relationship between CODparticulate and turbidity. This led to the
      conclusions that by introducing a dosing control strategy based on continuous
      turbidity measurements a constant CODparticulate removal efficiency can be
      obtained.

PMID- 11443991
TI  - Improved performance of a chitosan-based adsorbent for the sequestration of some
      transition metals.
AB  - Polyethyleneimine (PEI) was chemically introduced onto chitosan by its reaction
      with epoxide groups of grafted poly(glycidyl methacrylate) (poly(GMA)) chains for
      enhanced metal chelating properties and improved physical stability in acidic
      conditions. Graft polymerization of poly(GMA) onto chitosan was initiated by
      Ce(IV) ammonium nitrate (CAN). Infrared spectroscopy revealed the presence of
      significant epoxide groups to confirm the success of both grafting and amination
      stages. Batch adsorption experiments showed the higher affinity of the modified
      chitosan resin for Cu2+, Zn2+ and Pb2+. The capacity enhancement was even more
      pronounced in the case of Zn2+ and Pb2+, which exhibits more complicated three
      dimensional coordination requirements. Optimum metal adsorption occurs at above
      pH4. Regeneration of the resin with sulphuric acid-ammonium sulphate was also
      found to be feasible.

PMID- 11443992
TI  - Direct influent filtration as a pretreatment step for more sustainable wastewater
      treatment systems.
AB  - Within the scope of a research programme into wastewater treatment scenarios
      based on physical-chemical pretreatment, the application of direct influent
      filtration (DIF) as a first treatment step in a wastewater treatment system was
      investigated. The aim of the experimental research was to investigate the
      feasibility of DIF as a pretreatment step for advanced particle removal. With a
      large scale pilot-plant filter at WWTP Leiden-Noord, The Netherlands the removal
      characteristics for suspended and colloidal material were investigated as well as
      operational conditions of eight different filter configurations. From the
      experimental research it was concluded that filtration of raw wastewater is
      possible, notwithstanding the relatively short run-times due to clogging. In
      general, the filters produced a filtrate with a constant quality with low
      concentrations of solids and low turbidity. Without addition of chemicals hardly
      any colloids and solubles were retained, but only suspended particulates were
      removed. After dosage of iron or polymer, it was possible to remove more
      suspended matter and a high proportion of colloidal material. Finally it was
      concluded that DIF could be applied as a compact treatment system to produce a
      high quality primary effluent with a constant composition, but for practical
      application further research has to be done.

PMID- 11443993
TI  - Influence of pre-treatments and recycled flows on the COD fractions of a
      wastewater: a case study.
AB  - Physical-chemical and biological fractionation methods were used at different
      parts of the Evry WWTP in order to assess the influence of effluents recycled
      from the primary settling tanks and sludge treatment processes on the
      characteristics of the wastewater. The RBCOD doubled between the WWTP influent
      and the biological reactor inlet, thus doubling the denitrifying potential of the
      plant. The primary sludge gravity thickener effluent, subject to a great
      variability, appeared to contribute up to 38% of the RBCOD contained in the
      biological reactor influent, whereas only 30% seemed to come from the WWTP inlet.
      No notable increase of RBCOD was observed at the primary settling tanks' outlet
      for the longer residence time. The significant variations of RBCOD across the
      plant were not caused by fluctuations of the physical-chemical COD fractions.

PMID- 11443994
TI  - Phosphate, nitrogen and iron enrichment in the polluted Izmir Bay, Aegean Sea.
AB  - Izmir Bay is one of the most polluted estuaries in the Mediterranean Sea. The
      extent of pollution due to anthropogenic inputs in the Izmir Bay is investigated
      on the basis of nutrients together with basic oceanographic parameters.
      Significant phosphate, nitrogen (N) and iron (Fe) enrichment has been found in
      the water of inner Izmir Bay. The situation of middle Izmir Bay is also similar
      but not as critical as in inner Izmir Bay, whereas outer Izmir Bay shows 'typical
      Mediterranean coastal marine ecosystem' characteristics. The average atomic
      ratios of apparent oxygen utilization (AOU) and nutrient fractions (N and
      phosphorous [P]) have been found as AOU:P (49:1), AOU:N (48:1) and N:P (5:1). A
      comparative evaluation of these ratios leads to the conclusion that they are too
      low; e.g. such a low AOU:P ratio supports fairly high P enrichment. Principal
      component analysis (PCA) indicates that 31% of the variation in the data is
      related to enrichment parameters, i.e. dissolved inorganic phosphate, NH4+,
      reactive Fe, 15% is related to NO3-, pH and 13% is related to temperature and
      total Fe. Additionally, PCA shows that the middle Izmir Bay has an ecological
      transient character between the inner and outer Izmir Bay.

PMID- 11443995
TI  - Mytilus californianus as an indicator of heavy metals on the northwest coast of
      Baja California, Mexico.
AB  - Samples of Mytilus californianus were analyzed to determine the spatial and
      temporal distribution of Ag, Al, Cd, Cr, Cu, Mn, Pb and Zn concentrations on the
      northwest coast of Baja California and to compare the results with levels
      reported for California, USA. The samples were collected at eight sites from the
      US-Mexican border to San Quintin, BC (300 km south of the border) in February and
      July 1982 and 1994. During both years, north-south gradients in the concentration
      of Ag and Pb were observed, with the highest values close to the US-Mexican
      border (Ag = 0.60-1.54 and Pb = 0.21-2.89 micrograms g-1) and the lowest in the
      southern part of the study area (Ag = 0.05-0.10 and Pb = not detectable-0.03
      microgram g-1). The Ag and Pb gradients suggest that their distributions are
      affected by anthropogenic activities close to the US-Mexican border. South-north
      gradients in the concentration of Cd (minimum = 0.59-2.16 and maximum = 2.61
      12.93 micrograms g-1), for both 1982 and 1994, were observed. The geographic
      annual means of Pb for California (average of six stations along the entire
      state) were significantly higher than those of this study (average of the eight
      sampling sites) in 1982 and 1994. Cu in California was significantly greater than
      that of this study only in 1994. Cluster analyses on all metals indicate three
      similar geographic zones in 1982 and 1994, suggesting a relative consistency in
      the processes that determine the spatial variability of the concentration of some
      metals in M. californianus on the northwest coast of Baja California.

PMID- 11443996
TI  - Punctuated recovery of sediments and benthic infauna: a 19-year study of tailings
      deposition in a British Columbia fjord.
AB  - Sediment organic and metal chemistry, benthic infauna and tissue contaminants
      surveys have been conducted over 19 years before and following tailings
      deposition from a metal (Mo, Pb, Zn) mine in Alice Arm, a British Columbia fjord.
      We found changes in benthic fauna and habitat after tailings disposal to be
      predictable in terms of sediment chemistry and faunal recolonization. What was
      not predictable was the timing and extent of slope failure or resuspension
      following abandonment. These events can have essentially the same or greater
      effect than the initial tailings disposal and produce long-term unpredictability
      particular to cases of submarine disposal on slopes. The present study focused on
      the submarine deposition of 4 x 10(6) tonnes of tailings during an 18-months
      period ending October 1982. When the mine closed, gross defaunation had occurred
      at three stations in the tailings path, and two others showed recent defaunation
      and recolonization. A year later, a large tailings slump near the outfall
      transported tailings to the deep basin; fauna were impoverished both in the slump
      region and through most of the deep basin. Declining metal concentrations in
      surface sediments was accompanied by considerable recovery of fauna 3 years after
      the mine closed. Nevertheless, fauna at the three stations defaunated at the time
      of mine closure could still be statistically distinguished from all other
      stations due to high abundances of small opportunistic polychaetes and bivalves.
      A resuspension in tailings between 1988 and 1990 coincided with a moderate
      decline in abundance of all macrofauna taxa. From 1989 to 1995 recovery toward
      natural sediment conditions was evident as increasing organic content together
      with the highest faunal biomass values found during the study. Small polychaetes
      were the first recolonizers in defaunated areas, whereas small bivalves were more
      tolerant of moderate tailings deposition. By 1989 and 1995 small colonizers had
      declined and amphipods and larger echinoderms had increased. Dominant species
      patterns and exceptionally high biomass values in 1995 show that the largest
      fauna did not recover until much later than smaller taxa. One genus of bivalve
      (Yoldia spp.) accumulated metals in a pattern similar to the sediment chemistry,
      indicating that the metals from the most recent mine had entered the benthic food
      chain. It is not possible to tell from this study whether biota were affected by
      toxicity from metals. However, many of the observed biotic effects could be
      caused by physical disruption from tailings.

PMID- 11443997
TI  - Micropollutants and organic carbon concentrations in surface and deep sediments
      in the Tunisian coast near the city of Sousse.
AB  - A radioactive tracer was used to map the plume of the effluent of a municipal
      water treatment plant located on the Tunisian coast, close to the city of Sousse.
      A sampling campaign was programmed on the basis of the radioactivity
      distribution. The extent of sediment contamination was investigated to determine
      the impact of the plant effluent. Organic carbon and organic micropollutants
      (PCBs and chlorinated pesticides) were analysed on resuspendable particulate
      matter, on grab and core sediments. The area distributions of different compounds
      analysed were studied and relationships were investigated between radioactivity
      and organic carbon and micropollutant data. The study shows that sludge particles
      are deposited and accumulate in the zone south of the effluent outlet,
      contaminating sediments. Good correlations were found which demonstrate the
      efficiency of the technique used to plan the sampling and the link between
      organic carbon and organic micropollutants.

PMID- 11443998
TI  - Status of persistent organic pollutants in the sediment from several estuaries in
      China.
AB  - Sediment samples from three estuaries on the east coast of China were analyzed
      for persistent organic pollutants. Total PCB, PAH, and DDT concentrations in the
      sediments from Minjiang, Jiulongjiang, and Zhujiang estuaries ranged from 2 to 14
      ng/g, 400 to 1500 ng/g, and 6 to 73 ng/g, respectively, in the sediments from
      these estuaries. The sources of PAH contamination were inferred from PAH
      compositions, with pyrogenic PAHs being the dominant source for Minjiang Estuary
      and petroleum related PAHs being the primary contributors to Jiulongjiang and
      Zhujiang estuaries. The high concentrations of DDT in the sediments from these
      estuaries were likely the result of widespread use of DDT in China in the 1960s
      and 1970s. Butyltin compounds were detected in the sediment from Jiulongjiang
      Estuary and Victoria Harbor, Hong Kong. Presence of butyltin compounds probably
      result from the shipping activities in these estuaries. Butyltin compounds were
      not detected in the sediments from Minjiang and Zhujiang estuaries. Contaminant
      concentrations were generally below levels expected to affect benthic organisms
      with the exception of DDTs.

PMID- 11443999
TI  - Mercury concentrations in deer mouse (Peromyscus maniculatus) tissues from Isle
      Royale National Park.
AB  - We used deer mice (Peromyscus maniculatus) to investigate variation in mercury
      exposure across the terrestrial ecosystem of Isle Royale National Park (Michigan,
      USA). Although previous work suggested that mercury (Hg) levels may be higher
      inside the Sargent Lake watershed of Isle Royale than outside the watershed, Hg
      concentrations in livers were higher outside the Sargent Lake watershed (100.13
      ng Hg/g dry tissue) than inside the watershed (35.50 ng Hg/g dry tissue; P =
      0.06). Mercury levels in kidneys did not differ significantly (P = 0.57) between
      samples collected outside (443.23 ng Hg/g dry tissue) and inside (360.62 ng Hg/g
      dry tissue) the Sargent Lake watershed. Mean Hg concentrations in the livers of
      mice at some sites in Isle Royale are not significantly lower (P = 0.62) than Hg
      concentrations considered by some government agencies to be unhealthy for human
      consumption. Although Hg concentrations in mouse tissues were not remarkably high
      (compared to heavily polluted sites), concern is warranted because: (1) Isle
      Royale National park is a protected area in a remote location; (2) any exposure
      in deer mice represents a path for biomagnification in the terrestrial food web;
      and (3) the source of this mercury remains unidentified.

PMID- 11444000
TI  - Effect of composting on characterization and leaching of copper, manganese, and
      zinc from swine manure.
AB  - This research was conducted to study the influence of composting on the
      concentrations, water solubility, and phase association of Cu, Mn, and Zn from
      swine (Sus domesticus) feces. Composting of separated swine manure was performed
      in two piles for 122 days. The metal concentrations increased rapidly during the
      first 49 days and leveled off thereafter. All metal concentrations increased
      approximately 2.7-fold in the final compost due to decomposition of organic
      matter. A sequential extraction protocol was used to evaluate the humification
      process and partition metals into water-soluble, exchangeable, organically
      complexed, organically bound, solid particulate, and residual fractions. Temporal
      changes in the water-soluble fractions of Cu, Mn, and Zn were reflected by water
      soluble organic C concentrations, which rapidly increased to a maximum at Day 18
      and declined thereafter. An increase in the humic acid/fulvic acid ratio in
      Na4P2O7 or NaOH extracts at various stages of composting represented the
      humification process. During composting, the major portions of Cu, Mn, and Zn
      were in the organically-bound, solid particulate, and organically complexed
      fractions, respectively. Metal distributions in different chemical fractions were
      generally independent of composting age and, thus, independent of respective
      total metal concentrations in the composts.

PMID- 11444001
TI  - Toxicological response of a bioluminescent microbial assay to Zn, Pb and Cu in an
      artificial soil solution: relationship with total metal concentrations and free
      ion activities.
AB  - The relationship between toxicological response and both total concentrations and
      free ion activities of Pb, Cu and Zn in an artificial soil solution has been
      investigated using lux-marked Escherichia coli HB101 (pUCD607) as a bioassay.
      SO4(2-) (as K2SO4) was added as an inorganic complexing agent up to 0.01 M
      representing the range of ionic strengths found in soil solutions and giving a
      wide range of free metal ion activities. EC50 values expressed in terms of
      concentration, varied significantly with K2SO4 molarity for all metals. However,
      when EC50 values were expressed in terms of free ion activity they were not
      significantly different for Pb and Zn, supporting the free ion activity model.
      Conversely, EC50 values expressed as free Cu activity did vary significantly with
      K2SO4 molarity, possibly due to a greater degree of adsorption of Cu onto
      inactive sites on the cell surfaces than for Zn and Pb. Linear regression
      analysis of bioluminescence on free ion activity revealed significant
      correlations for each metal above the toxicity threshold. In conclusion, lux
      marked E. coli is suitable for investigating the toxicity of metal ions and
      complexes in non saline systems although cell surface adsorption effects could be
      important for some metals, e.g. Cu.

PMID- 11444002
TI  - Is it possible to develop a QSPR model for direct photolysis half-lives of PAHs
      under irradiation of sunlight?
AB  - By the use of the partial least squares method and 11 fundamental quantum
      chemical descriptors computed from the PM3 Hamiltonian, a Quantitative Structure
      Property Relationship model was obtained for direct photolysis half-lives of
      selected polycyclic aromatic hydrocarbons (PAHs) under irradiation of sunlight.
      Direct photolysis half-lives for some other PAHs without reported values were
      predicted. It was concluded from the model that the main factors affecting
      photolysis half-lives of PAHs under irradiation of sunlight are PAH absolute
      hardness and electronegativity, which are related to the energy difference
      between the lowest unoccupied molecular orbital and the highest occupied
      molecular orbital, (Elumo - Ehomo) and (Elumo + Ehomo), respectively. Increasing
      Ehomo and the average molecular polarizability (alpha) values of the PAHs leads
      to decrease of photolysis half-lives. Increasing (Elumo - Ehomo) and Elumo values
      of the PAHs leads to an increase of the PAH photolysis half-lives.

PMID- 11444003
TI  - Effects of vapours of chlorpropham and ethofumesate on wild plant species.
AB  - Effects of vapours of two herbicides on plantlets of fourteen wild higher plant
      species and two bryophytes were screened in fumigation experiments using foliar
      injury, chlorophyll fluorescence and growth as response parameters. After
      vaporisation of the herbicides for 48 h, concentrations in the chambers reached
      77 micrograms m-3 in the chlorpropham treatments and 184 ng m-3 in the
      ethofumesate treatments. Despite the higher concentrations of the volatile
      chlorpropham (vapour pressure, VP: 1.3 mP), plants showed no foliar injury, but
      vapours of this herbicide caused leaf crinkling in the agriophyte Agrostemma
      githago. The less volatile ethofumesate (VP: 0.56 mP) caused foliar injury in all
      higher species, with lowest no observed effect concentrations (NOECs) of 75 ng m
      3. Chlorpropham affected growth only in Agrostemma, while ethofumesate reduced
      growth in one third of the higher plant species. Chlorophyll fluorescence proved
      to be a less suitable response parameter compared to foliar injury and growth. No
      adverse effects were observed in mosses, probably due to the slow growth and
      hence small doses of herbicides taken up. The extent of foliar injury due to
      ethofumesate showed a weak positive relationship to relative growth rates and
      specific leaf area in the tested higher plant species.

PMID- 11444004
TI  - Dissolved and colloidal transport of Cd, Pb, and Zn in a silt loam soil affected
      by atmospheric industrial deposition.
AB  - As a result of processing of metal ores, trace metals have contaminated large
      areas of northern France. Metal migration from the soil to groundwater presents
      an environmental risk that depends on the physico-chemical properties of each
      contaminated soil. Soil water samples were obtained over the course of 1 year
      with zero-tension lysimeters from an acidic, loamy, metal contaminated soil. The
      average trace metal concentrations in the soil water were high (e.g. for Zn 11 mg
      l-1 under the surface horizon), but they varied during the sampling period. Zn
      concentrations were not correlated with pH or total organic carbon in the
      solutions but were correlated with Cd concentrations. On average, 95% of the Zn
      and Cd but only 50% of Pb was present in a dissolved form. Analytical
      transmission electron microscopy was used to identify the Zn or Pb carriers.
      Colloids containing Pb and Zn were biocolloids, whereas colloids containing only
      Zn were smectites.

PMID- 11444005
TI  - Contaminant residues in seabird eggs from the Canadian Arctic. Part I. Temporal
      trends 1975-1998.
AB  - Concentrations of total mercury, selenium and a suite of organochlorine compounds
      were measured in eggs of thick-billed murres (Uria lomvia), northern fulmars
      (Fulmarus glacialis) and black-legged kittiwakes (Rissa tridactyla) collected on
      Prince Leopold Island in Lancaster Sound, Nunavut, Canada, between 1975 and 1998.
      Mercury levels in thick-billed murre and northern fulmar eggs increased
      significantly during this period while selenium concentrations decreased
      significantly in northern fulmar eggs. Mercury and selenium concentrations in
      black-legged kittiwake eggs exhibited no significant temporal trends.
      Concentrations of sigma PCB, sigma DDT and total chlorobenzenes decreased over
      time for all three species and there was a shift in the PCB congener pattern as
      the hexachlorobiphenyl fraction of sigma PCB increased and the lower chlorinated
      biphenyl fraction decreased. Total chlordane, dieldrin and mirex concentrations
      decreased in kittiwake eggs while no significant trends were observed for the
      other two species. Increases in sigma HCH levels were detected in thick-billed
      murre eggs but not in northern fulmar and black-legged kittiwake eggs. Levels of
      the beta-HCH isomer, however, increased significantly in murres and fulmars.
      Stable-nitrogen isotope analyses (delta 15N) indicate that the temporal trends
      observed for contaminant concentrations in eggs were not the result of shifts in
      trophic level. Changing deposition patterns of xenobiotic compounds over the
      summer and winter ranges of these birds provide a likely explanation for
      differing exposures through time.

PMID- 11444006
TI  - The seasonal changes in the concentration of polycyclic aromatic hydrocarbons in
      precipitation and aerosol near Lake Balaton, Hungary.
AB  - The concentration of polycyclic aromatic hydrocarbons (PAHs) in atmospheric
      precipitation and aerosol samples was monitored in a rural site by Lake Balaton,
      Hungary to examine the seasonal variation. The seasonal mean concentration of
      individual 3-6-ring PAHs in precipitation varied from 1 to 54 ng l-1 and from 3
      to 350 ng l-1 in summer and winter, respectively. In the atmospheric aerosol
      samples the seasonal mean concentration of PAHs varied from 4 to 880 pg m-3, from
      4 to 300 pg m-3, from 11 to 1050 pg m-3 and from 36 to 5000 pg m-3 in spring,
      summer, autumn and winter, respectively. Wet (412 micrograms m-2 year-1) and
      aerosol (190-300 micrograms m2 year-1) deposition rates were also estimated
      indicating that the two processes are of comparable importance in the removal of
      3-6-ring PAHs from the atmosphere.

PMID- 11444007
TI  - Heavy metal budgets for two headwater forested catchments in background areas of
      Finland.
AB  - Mean annual (1994-1996) budgets for Cd, Cu, Ni, Pb and Zn at two background,
      forested catchments, VK and HJ, in Finland are presented. Budgets for plots (VK3,
      HJ1 and HJ4) included throughfall (TF), litterfall (LF) and soil leaching fluxes,
      and for catchments terrestrial retention and leaching and lake sedimentation
      fluxes. Total deposition (TD) loads were relatively low (Cd < 0.1, Cu < 2, Ni <
      1, Pb < 3 and Zn < 5 mg m-2 year-1) and that even in these areas almost half of
      the TD was in the form of dry deposition. Retention of TD within catchments was >
      or = 77% for all metals, except for Ni at VK (54%). For Cu and Pb, the retention
      was 94-97%. Most of the retention (74-97%) took place in the terrestrial part of
      the catchment, lake sedimentation accounting for the remainder. Plot-scale soil
      leaching fluxes at 40 cm of Cd, Cu (VK3) and Ni (VK3) were greater (> or = 100%)
      than TD inputs. Most of the catchment retention must therefore have taken place
      either deeper in the soil or in the lowland peatland areas. The humus layer was
      particularly effective in retaining Cu and Cd (65-81% and 51-78% of total inputs
      to the forest floor (TF + LF)). The retention of Pb by the humus layer was less
      than expected (26-54% of TF + LF). Litterfall was a particularly important
      internal flux for Zn.

PMID- 11444008
TI  - Metal extraction by Arabidopsis halleri grown on an unpolluted soil amended with
      various metal-bearing solids: a pot experiment.
AB  - Most studies dealing with phytoremediation have considered metal extraction
      efficiency in relation to metal concentration of bulk soil samples or metal
      concentration of the soil solution. However, little is known about the effect of
      various metal-bearing solids on plant growth and metal extraction of
      hyperaccumulators. In this study, we investigated the ability of Arabidopsis
      halleri to grow and extract metals from different substrates consisting in an
      unpolluted soil amended with various metal-bearing solids collected in soils
      around a Zn smelter complex. The metal-bearing solids used as amendments were:
      fresh and decomposing organic residues in the soil, a soil clay fraction and two
      waste slags. Pure mono-metallic salt (ZnSO4) was also used. Two series of
      substrates were produced, one moderately polluted, and the other highly polluted.
      An additional substrate was formed by the unamended soil, and used as an
      unpolluted control. Zn, Cd, Cu, and Pb were measured in the substrates, and in
      the roots and shoots of A. halleri. The dry matter yield of A. halleri was shown
      not to depend on the nature of the metal-bearing solid used, except when Cu
      toxicity was suspected. On highly-polluted substrates, Zn extraction by A.
      halleri depended on the nature of metal-bearing solids used, showing the
      following trend: pure mono-metallic salt > waste slags and soil clay fraction >
      fresh and decomposing organic matter. We explained these differences by the high
      solubility of Zn in the mono-metallic salt, whereas in the mineral metal-bearing
      solids and in both fresh and decomposing organic matter, Zn release required
      mineral weathering or organic matter mineralization, respectively. This work
      clearly showed that phytoremediation studies have to consider the nature of metal
      bearing solids in contaminated soils to better predict the efficiency of plant
      extraction.

PMID- 11444009
TI  - Repeated use of two Chlorella species, C. vulgaris and WW1 for cyclic nickel
      biosorption.
AB  - Two living Chlorella species were used to remove nickel from solution containing
      30 micrograms Ni ml-1 in 10 successive cycles. The present study also examined
      the continued viability of these two algal species after repeated exposure to
      nickel. The two species of Chlorella were Chlorella vulgaris (commercially
      available) and WW1 (indigenous species isolated from domestic sewage and was
      tentatively identified as Chlorella miniata). The nickel removal percentage of
      WW1 cells was maintained at around 85% in the first five cycles, then declined
      slightly from the fifth cycle onwards, and finally achieved around 70% removal at
      the end of the 10th cycle. On the contrary, the removal efficiency of C. vulgaris
      declined from 50 to 30% during the 10 cycles of nickel bisorption. At the end of
      these 10 successive cycles, WW1 accumulated a substantial amount of Ni2+ (the
      cumulative cellular Ni concentration was 0.92% dry w.), while the value was only
      0.17% in the case of C. vulgaris. These results suggest that the local isolate,
      WW1, had more consistent and satisfactory ability for removing Ni than the
      commercial C. vulgaris. Both algal species were still capable of dividing after
      each nickel treatment cycle, suggesting that the cells were not killed even when
      significant amounts of nickel were adsorbed/absorbed. However, Ni exposure
      adversely affected the physiological activity of algal cells as reflected by the
      decline in division rate and chlorophyll-a activity in both species. Such
      negative effects became more obvious as the number of cyclic treatments was
      increased. Nevertheless, WW1 cells appeared to recover from nickel treatment when
      re-cultivated in commercial medium for 2 weeks.

PMID- 11444010
TI  - Accumulation of Al, Mn, Fe, Cu, Zn, Cd and Pb by the bryophyte Scapania undulata
      in three upland waters of different pH.
AB  - Measurements were made of the contents of Al, Mn, Fe, Cu, Zn, Cd and Pb in
      Scapania undulata in three streams (D2, D5, D11) in the English Lake District.
      The stream waters had average pH values of 5.35 (D2), 5.81 (D5) and 7.26 (D11),
      the main differences in other major chemical components being in Mg, Al, Ca and
      alkalinity. There was generally more metal accumulation in the older parts of the
      plants, but this was not significant in all cases. Extents of accumulation varied
      with stream pH and dissolved metal concentration. For Al, accumulation was
      greatest in streams D2 and D5. Mn accumulated most in D5 and Fe was without
      preference. Cu, Zn and Cd accumulated mostly in the plants in stream D11 and Pb
      accumulated more in D5 and D11. In terms of enrichment factors (amount of metal
      in the plants divided by stream water concentration) the sequence was Zn < Cd <
      Cu < Mn < Pb < Al < Fe. Laboratory experiments supported the findings of the
      field data, providing evidence that uptake increases with pH at constant total
      metal concentration. The results are interpreted qualitatively in terms of the
      chemical speciation of the metals in the stream water and competition between
      metal ions and protons at the plant-water interface. It is suggested that Al, Cu,
      Zn, Cd and Pb behave according to chemical complexation, whereas redox processes
      and/or colloidal interactions may be significant for Mn and Fe.

PMID- 11444011
TI  - Critical evaluation of an intercalibration exercise undertaken in the framework
      of the MED POL biomonitoring program.
AB  - The results of an intercalibration exercise among the laboratories participating
      in the MED POL program for monitoring biological effects of pollutants along the
      Mediterranean coasts are presented. Three established biomarkers, i.e. lysosomal
      membrane stability, metallothionein concentration and ethoxyresorufin-O
      deethylase (EROD) activity, were intercalibrated. The stability of lysosomal
      membranes in mussels (Mytilus galloprovincialis Lam.) was assessed with a
      cytochemical method. The four participating laboratories were able to
      discriminate between control animals (membrane labilization times ranging from 21
      to 35 min) and Cu-exposed animals (40 micrograms/l Cu for 3 days) (labilization
      times ranging from 4.5 to 7.4 min). The metallothionein concentration was
      evaluated in digestive gland homogenates of control mussels and of animals
      exposed to 200 micrograms/l Cd for 7 days. The eight participating laboratories
      were able to discriminate between controls and treated samples using a
      spectrophotometric method. The EROD activity was evaluated by 11 laboratories.
      All laboratories were able to discriminate between liver microsomal preparations
      obtained from control and from benzo-a-pyrene exposed fish (Dicentrarchus
      labrax), with values ranging from 0.5 to 15.88 pmol/min/mg protein in controls
      and from 5.41 to 165.13 pmol/min/mg protein in treated animals. Using S9
      fractions, it was possible to correctly identify control and treated fish, with a
      variation similar to that found using microsomal fractions, albeit with an
      inevitable difference in specific activity. As a corollary, all laboratories
      involved produced comparable data and were able to identify pollutant-induced
      stress syndromes in sentinel organisms. Thus, intercalibration enables the use of
      biomarkers in large biomonitoring programs.

PMID- 11444012
TI  - Organic contaminant distributions in sediments, polychaetes (Nereis virens) and
      American lobster (Homarus americanus) from a laboratory food chain experiment.
AB  - A laboratory experiment was conducted to investigate the transfer of organic
      contaminants from an environmentally contaminated marine sediment through a
      simple marine food chain. The infaunal polychaete, Nereis virens, was exposed to
      contaminated sediment collected from the Passaic River, NJ, USA, for 70 days.
      These polychaetes were then fed to the American lobster, Homarus americanus, for
      up to 112 days. Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), 2,4,6,8-tetrachlorodibenzothiophene (TCDT),
      polychlorinated biphenyls (PCBs), and several chlorinated pesticides were
      accumulated by polychaetes following exposure to the contaminated sediment. Some
      of these contaminants were also accumulated by lobsters which were exposed to the
      contaminated sediment and/or fed contaminated polychaetes. Only the lesser
      chlorinated PCDDs and PCDFs (mostly tetra- and pentachlorinated congeners) and
      2,4,6,8-TCDT were detected in the polychaetes and lobster. Significant
      alterations were noted in the PCB patterns found in both species, particularly
      the lobster. The non-ortho-substituted PCBs (such as congeners 77 and 126) became
      enriched in the PCB mixtures of the polychaetes and especially the lobsters
      relative to the sediment, probably because these congeners were not metabolized.
      These congeners and the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents
      of the PCB mixtures were enriched by a factor of about six in the lobsters
      relative to the sediment. Elimination of PCB congeners containing vicinal
      hydrogens in the meta-para region is consistent with cytochrome P450IIB-type
      metabolism. Based on the concentration trends for some PCB congeners and
      chlorinated pesticide ratios measured in the lobsters during this experiment, it
      appears that this metabolic system is inducible in the American lobster.

PMID- 11444013
TI  - Elevated serum vitellogenin levels and gonadal abnormalities in wild male
      flounder (Pleuronectes yokohamae) from Tokyo Bay, Japan.
AB  - Concentrations of vitellogenin (VTG) in serum of wild male flounder (Pleuronectes
      yokohamae) were investigated, as a biomarker for environmental estrogens in
      marine waters, from January 1997 to May 1998 in Tokyo Bay, Japan (n = 130) and
      from a reference site in Hokkaido, Japan, far from urban areas (about 40 km from
      Hakodate city) from March 1997 to June 1998 (n = 62). Statistically higher
      concentrations of serum VTG were detected in wild male flounder collected in
      Tokyo Bay (range: 25-2200 ng ml-1) compared to fish from Hokkaido (range: 31-91
      ng ml-1) throughout the entire sampling period. Three out of 20 males collected
      off Haneda, in the inner part of Tokyo Bay, showed testes containing small
      numbers of oocytes. This intersex condition was not found among males collected
      from the reference site. This study suggests that the abnormally high levels of
      VTG and the presence of oocytes in the testis of male flounder collected from
      Tokyo Bay could be the effect of environmental estrogens.

PMID- 11444014
TI  - Tissue distribution of metals in striped dolphins (Stenella coeruleoalba) from
      the Apulian coasts, southern Italy.
AB  - Tissue distributions of metals (mercury, lead, cadmium, zinc, copper, iron,
      manganese) were determined in six specimens of striped dolphins (Stenella
      coeruleoalba, Meyen) stranded on the Apulian coasts (Southern Italy) between
      February and June 1987. Methyl mercury and selenium were also determined in the
      liver samples. The liver accumulated the highest concentrations of metals, except
      for cadmium and chromium. Metal levels were higher than those found in dolphins
      living in the Atlantic, but lower than those recorded in the same species from
      the French Mediterranean coasts. Necroscopic surveys found that all specimens
      were affected by haemorrhagic gastritis, but the cause was not clear. While it
      was not possible to related the death of dolphins to a specific cause, or to
      contaminants, the accumulation of metals is likely to contribute to the health of
      the organism and represents a risk factor for dolphins.

PMID- 11444015
TI  - Evaluating environmental contamination in Ria Formosa (Portugal) using stress
      indexes of Spartina maritima.
AB  - Species of Spartina are potentially useful for biomonitoring coastal systems
      because they are abundant in the intertidal and have a wide geographic
      distribution in temperate zones. In this study, three indexes of physiological
      stress, thiolic protein concentration, adenylic energy charge (AEC) index [AEC =
      ATP + 0.5ADP/(ATP + ADP + AMP)] and photosynthetic efficiency (Fv/Fm), are
      measured in Spartina maritima plants collected at four sites and compared with
      metal concentrations in the sediments and Spartina tissues. Two sites were close
      to urban centers and two were located further away, in less contaminated areas.
      Concentrations of copper, cadmium, lead and zinc were determined by atomic
      absorption spectrophotometry, thiolic proteins were determined by polarography
      and adenilic nucleotides were determined by high performance liquid
      chromatography. Photosynthetic efficiencies were measured with a fluorometer. The
      sediments of sites closer to urban centers had higher concentrations of metals
      than the sites located further away. Metal concentration within plants did not
      follow this spatial pattern, probably due to spatial differences in metal
      bioavailability, uptake rates, internal transport and excretion processes.
      Concentrations of all metals studied were higher in underground plant structures
      than aerial, except cadmium whose levels were not significantly different. On the
      other hand, the stress indexes followed the spatial pattern of metals in the
      sediment. Thiolic protein concentrations were higher in plants from polluted
      sites, and were three to four times higher in aerial than in underground plant
      structures. Leaf AEC ratios and photosynthetic efficiencies were lower in plants
      from polluted sites indicating that they were growing under stressful conditions.
      We conclude that the use of these indexes in S. maritima represent a useful tool
      to monitor contamination in Ria Formosa lagoon as they provide an integrated
      measure of the toxicological burden of contamination.

PMID- 11444016
TI  - Development of an air bubble curtain to reduce underwater noise of percussive
      piling.
AB  - Underwater bubbles can inhibit sound transmission through water due to density
      mismatch and concomitant reflection and absorption of sound waves. For the
      present study, a perforated rubber hose was used to produce a bubble curtain, or
      screen, around pile-driving activity in 6-8-m depth waters of western Hong Kong.
      The percussive hammer blow sounds of the pile driver were measured on 2 days at
      distances of 250, 500, and 1000 m; broadband pulse levels were reduced by 3-5 dB
      by the bubble curtain. Sound intensities were measured from 100 Hz to 25.6 kHz,
      and greatest sound reduction by the bubble curtain was evident from 400 to 6400
      Hz. Indo-Pacific hump-backed dolphins (Sousa chinensis) occurred in the immediate
      area of the industrial activity before and during pile driving, but with a lower
      abundance immediately after it. While hump-backed dolphins generally showed no
      overt behavioral changes with and without pile driving, their speeds of travel
      increased during pile driving, indicating that bubble screening did not eliminate
      all behavioral responses to the loud noise. Because the bubble curtain
      effectively lowered sound levels within 1 km of the activity, the experiment and
      its application during construction represented a success, and this measure
      should be considered for other appropriate areas with high industrial noises and
      resident or migrating sound-sensitive animals.

PMID- 11444017
TI  - Genetic studies of Psammolestes tertius (hemiptera: reduviidae: triatominae)
      using male genital morphology, morphometry, isoenzymes, and random amplified
      polymorphic DNA.
AB  - Two Brazilian populations of Psammolestes tertius (Ceara and Minas Gerais)
      collected from thornbird nests (Furnariidae) were compared by male genital
      morphology, morphometry, isoenzymes, and random amplified polymorphic DNA (RAPD).
      Male genitalia showed no difference between the populations. In contrast,
      morphometry, isoenzyme, and RAPD clearly distinguished the two populations.
      Possible mechanisms of dispersal and the origin of Psammolestes are discussed.

PMID- 11444018
TI  - Complementation cloning and characterization of the pyrroline 5-carboxylate
      reductase gene from Drosophila melanogaster.
AB  - The first insect cDNA and genomic sequences encoding pyrroline 5-carboxylate
      reductase (EC 1.5.1.2) have been isolated from Drosophila melanogaster. The cDNA
      sequence was identified by interspecies complementation of an E. coli proline
      auxotroph and encodes a protein 280 amino acids in length with 25-41% identity to
      pyrroline 5-carboxylate reductases isolated from other organisms. The
      corresponding gene is single copy and is located at cytological position 91E-F,
      and in one of the P1 clones in that region. With a single 61-bp intron, and an
      impressively small 135- to 200-bp region that presumably acts as a bidirectional
      promoter, the gene itself shows remarkable economy. The calculated molecular
      weight of 29,700 predicts that the native enzyme is likely an octomer. Sequencing
      of the promoter region and expression studies, as well as the known function of
      the enzyme in redox regulation and the high levels of free proline in insects,
      suggest that this housekeeping gene encodes an enzyme with a crucial role in
      intermediary metabolism.

PMID- 11444019
TI  - cDNA of a novel mRNA expressed predominantly in mouse kidney.
AB  - We examined embryonic carcinoma (EC) cells for a potential prototype molecule of
      C3, the third component of complement. PCR primers, corresponding to the base
      sequence derived from the C3 cDNA of several species, were used for PCR
      amplification of the EC cell cDNA. All the PCR products obtained had the same
      sequence and showed no sequence homology to C3. Subsequently, cDNA clones were
      isolated from a mouse liver cDNA library using the PCR product as a probe.
      Unexpectedly, neither the base sequence of the cDNA clones nor the amino acid
      sequence deduced from the cDNA showed homology to C3, although partial homology
      was observed to a number of sequences from EST databases. We designated this new
      clone NCU-G1. Northern hybridization experiments revealed that NCU-G1 is
      expressed constitutively not only in the mouse fetus but also in various mouse
      tissues, and is most abundant in the kidney cortex.

PMID- 11444020
TI  - Genetic variation in Indian populations of Scirpophaga incertulas as revealed by
      RAPD-PCR analysis.
AB  - Scirpophaga incertulas, commonly referred to as yellow stem borer, is a
      predominant pest of rice causing serious losses in its yield. Genetic variation
      among populations of Scirpophaga incertulas collected from 28 hotspot locations
      in India was examined using the randomly amplified polymorphic DNA-polymerase
      chain reaction (RAPD-PCR). In all, 32 primers were used and 354 amplification
      products were observed. No RAPD-PCR bands diagnostic to the pest population from
      any specific region were identified. Cluster analysis using UPGMA showed that,
      with the exception of the pest population from Pattambi, all the populations
      cluster as one group with GD values in the range of 6-22%, suggesting that gene
      flow between populations is independent of geographic distance and appears to be
      unrestricted. The relatively high GD value of 48% exhibited by the pest
      population from Pattambi was the only exception.

PMID- 11444021
TI  - Characterization of baboon (Papio hamadryas) milk proteins.
AB  - The major proteins of baboon milk were identified as beta-lactoglobulin (beta
      LG), alpha-lactalbumin (alpha LA), lysozyme, lactoferrin, casein, and albumin by
      immobiline isoelectric focusing, SDS-PAGE, immunoblotting of gels with rabbit
      antisera to human alpha LA, lysozyme, and albumin and bovine beta LG and casein,
      and N-terminal sequencing of proteins blotted from gels. The first 30 N-terminal
      residues of baboon beta LG are identical to those of macaque (Macaca fasicularis)
      beta LG except for a (D/N) polymorphism at residue 2. The complete cDNA sequence
      and derived amino acid composition of beta LG were elucidated using RT-PCR
      amplification of poly(A)+ mRNA purified from lactating mammary gland. Baboon beta
      LG consists of 168 amino acid residues (M(r) 20,750) and is the longest beta LG
      identified to date. beta LG and alpha LA polymorphisms with three (A, B, and C)
      and two (A and B) variants, respectively, were detected by immobiline IEF, pH 4
      6, of individual baboon milk samples at varying stages of lactation.

PMID- 11444022
TI  - Reduced enzyme activity following Hsp70 overexpression in Drosophila
      melanogaster.
AB  - Acclimation to environmental change can impose costs to organisms. One potential
      cost is the change in cell metabolism that follows a physiological response,
      e.g., high expression of heat shock proteins may alter specific activity of
      important enzymes. We examined the significance of this cost in a pair of
      Drosophila melanogaster lines transformed with additional copies of a gene that
      encodes the heat shock protein, Hsp70. Heat shock induces Hsp70 expression in all
      lines, but lines with extra copies produce much more Hsp70 than do excision
      control strains. The consequence of this supranormal Hsp70 expression is to
      reduce specific activity of both enzymes analyzed, adult alcohol dehydrogenase
      (ADH), which is heat sensitive, and lactate dehydrogenase, which is not. Strain
      differences were most pronounced under those conditions where Hsp70 expression
      was maximized, and not where the heat stress denatured proteins. That result
      supported the idea that Hsp70 expression is constrained evolutionarily by its
      tendency to bind nascent peptides when overabundant within the cell.

PMID- 11444023
TI  - Correlates of protection against rotavirus infection and disease.
AB  - Repeated infections with the 'mucosal' pathogen rotavirus are common in children.
      Subsequent rotavirus infections usually cause milder symptoms than first-time
      infections. Therefore, although natural rotavirus infection attenuates the
      severity of subsequent infections, it does not prevent reinfection or mild
      disease. On the other hand, natural infection with 'systemic' viruses such as
      measles, mumps, rubella, or varicella often confers life-long protection against
      mild disease associated with reinfection. The degree to which differences in the
      pathogenesis of systemic and mucosal pathogens determines differences in the
      capacity of natural infection to induce life-long protective immunity will be
      discussed. This paradigm will be used to explore the immunological effector
      functions associated with protection against rotavirus challenge.

PMID- 11444024
TI  - Rotavirus epidemiology and surveillance.
AB  - There is extensive antigenic and genomic diversity among co-circulating human
      rotaviruses. They are differentiated into groups, subgroups and types. There are
      at least 7 groups (A-G) and 4 subgroups within group A. To distinguish types
      within group A, a dual classification system has been established with the
      glycoprotein VP7 defining G types, and the protease-sensitive protein VP4
      defining P types. At least 14 G types and more than 20 P types have been
      distinguished, of which at least 10 G types and at least 11 P types have been
      found in humans. Using the typing system, the complex molecular epidemiology of
      rotaviruses was investigated. Rotaviruses of different G and P types co
      circulate. The main types found are G1P1A[8], G2P1B[4], G3P1A[8], G4P1A[8]; their
      relative incidence rates change over time in any one location and are different
      at the same time between different locations. Viruses with G/P constellations
      such as G1P1B[4] and G2P1A[8] are mostly natural reassortants of the co
      circulating main virus types emerging after double infection of hosts. Viruses
      carrying G and or P types not represented in the four most common types, e.g.
      G8P[8], G1P[6] or G9P[6], could be introduced into the population by reassortment
      with animal viruses, or directly from animals or exotic human sources. Naturally
      circulating rotaviruses constantly undergo point mutations which can be used to
      classify lineages and sublineages within types. The full significance of human
      infections with group B and C rotaviruses remains to be established. Surveillance
      of rotavirus types in different parts of the world is essential to monitor the
      emergence of new types or of new G/P constellations which may predominate over
      time. The efficacy and effectiveness of any future rotavirus vaccine may differ
      depending on the predominant natural strain types. Detailed epidemiological and
      molecular surveillance data should be utilized to study the transmission dynamics
      of rotaviruses.

PMID- 11444025
TI  - A rotavirus vaccine for prevention of severe diarrhoea of infants and young
      children: development, utilization and withdrawal.
AB  - The importance of rotaviruses (RVs) as the single most important cause of severe
      diarrhoea of infants and young children is well recognized. At NIH, we developed
      a quadrivalent (tetravalent [TV]) vaccine to protect against the four
      epidemiologically important RV serotypes. It is comprised of live attenuated
      rhesus RV (RRV), a VP7 serotype G3 strain (the 'Jennerian' approach), and three
      reassortant RVs, each containing 10 RRV genes and one human RV gene that codes
      for the major outer protein, VP7, that determines serotype G1, G2 or G4
      specificity (the 'modified Jennerian' approach). The vaccine was safe and
      effective against severe diarrhoea in a major prelicensure collaborative effort
      of phase III trials. In February 1998 and again in June 1998, the Advisory
      Committee on Immunization Practices (ACIP) recommended routine immunization with
      three oral doses at 2, 4 and 6 months of age. The tetravalent vaccine
      (RotaShield) was licensed in the USA by the FDA in August 1998. In July 1999,
      after about 1.5 million doses had been given, the CDC recommended suspending
      administration of the vaccine because post-licensure surveillance of adverse
      events had suggested an association with intussusception. After further
      investigation by CDC, in October 1999, the ACIP withdrew its recommendation
      concluding that '...intussusception occurs with significantly increased frequency
      in the first 1-2 weeks after vaccination with RRV-TV, particularly following the
      first dose'. The implications of these developments from a practical,
      epidemiological, analytical and ethical perspective are discussed.

PMID- 11444026
TI  - The molecular biology of human caliciviruses.
AB  - Within the last decade molecular analyses of the genome of Norwalk-like viruses
      (NLVs) have confirmed that this important group of infectious agents belongs to
      the Caliciviridae family. NLVs have a positive-sense, single-stranded RNA genome
      of approximately 7700 nucleotides excluding the polyadenylated tail. The genome
      encodes three open reading frames: ORF 1 is the largest (approximately 1700 amino
      acids) and is expressed as a polyprotein precursor that is cleaved by the viral
      3C-like protease; ORF 2 encodes the viral capsid (550 amino acids); and ORF 3
      encodes a small basic protein of unknown function. Comparative sequencing studies
      of human caliciviruses have revealed a second distinct group of viruses known as
      Sapporo-like viruses (SLVs). SLVs also have a single-stranded, positive-sense RNA
      genome of approximately 7400 nucleotides and the small 3' terminal ORF (NLV-ORF3
      equivalent) is retained. Phylogenetic analyses of NLV and SLV genomic sequences
      have assigned these viruses to two different genera with each genus comprised of
      two distinct genogroups. The fundamental difference in genome organization
      between NLVs and SLVs is that the polyprotein and capsid ORFs are contiguous and
      fused in SLVs. Progress in understanding the molecular biology of human
      caliciviruses is hampered by the lack of a cell culture system for virus
      propagation. Studies on viral replication and virion structure have therefore
      relied on the expression of recombinant virus proteins in heterologous systems.
      Norwalk virus capsid expressed in insect cells assembles to form virus-like
      particles (VLPs). Structural studies have shown that Norwalk virus VLPs are
      comprised of 90 dimers of the capsid protein.

PMID- 11444027
TI  - Molecular epidemiology of human enteric caliciviruses in The Netherlands.
AB  - Caliciviruses are among the most common causes of gastroenteritis in people of
      all age groups. These antigenetically and genetically diverse viruses have been
      grouped into two genera within the family Caliciviridae, designated Norwalk-like
      viruses (NLV) and Sapporo-like viruses (SLV). To gain more insight in their
      epidemiology, we have developed a tentative genotyping scheme, which was used to
      differentiate the viruses detected in a set of epidemiological studies. NLVs and
      SLVs were detected by generic RT-PCR in stool specimens from 5.1% and 2.4% of
      cases with acute gastroenteritis for which a general practitioner was consulted,
      and in 16.5% and 6.3% of community cases of gastroenteritis. In addition, NLVs
      were associated with more than 80% of reported outbreaks of gastroenteritis from
      1994-1999. Typically, several genotypes of NLV co-circulate in the community.
      Occasionally, however, several consecutive outbreaks were caused by essentially
      the same virus, although an epidemiological link had not previously been noted.
      This was most pronounced in 1995/1996, when a Lordsdale-like variant was detected
      that subsequently was found worldwide. This epidemic spread suggests differences
      in virulence or mode of transmission. In addition, we found that related NLVs are
      highly prevalent in calves in The Netherlands, raising questions about their
      potential for zoonotic transmission.

PMID- 11444028
TI  - Molecular biology of astroviruses: selected highlights.
AB  - Human astrovirus, the prototype of the Astroviridae family, is a non-enveloped
      positive-strand RNA virus with distinctive morphology. Initially named for a
      characteristic 5-6 point star evident on the surface of faecally shed viral
      particles by direct electron microscopy, a recent study using cryoelectron
      microscopy and image reconstruction indicates that viral particles consist of a
      smoothly rippled, solid capsid decorated with short spikes. Mechanisms underlying
      the assembly of these viral particles have not been fully elucidated. However,
      studies of two full-length cDNA clones of human astrovirus serotype 1 suggest
      that capsid residue Thr227 plays a critical role in the assembly of infectious
      viral progeny. The development of a full-length clone (pAVIC) from which
      infectious RNA can be transcribed has also facilitated studies of the viral 3C
      like serine protease, encoded in ORF1a. These studies demonstrate that the full
      length ORF1a product (101 kDa) is processed in vitro to an N-terminal 64 kDa
      fragment and a C-terminal 38 kDa fragment. Mutation of the predicted catalytic
      triad inhibits proteolysis. In other studies based on modifications of pAVIC,
      preliminary evidence supports the feasibility of developing a reporter cell line
      to facilitate astrovirus detection.

PMID- 11444029
TI  - Molecular epidemiology of human astroviruses.
AB  - Human astroviruses (HAstVs) are associated with 5-9 percent of cases of
      gastroenteritis in young children. Seven serotypes (HAstV-1 to -7), which
      correlate with genotypes, have been defined by using immune typing methods. We
      have used partial nucleotide sequence information from the capsid protein gene
      for molecular typing of 29 unique human astrovirus strains obtained from
      prospective studies of children with gastroenteritis in Egypt and Malawi. HAstV-1
      was the most commonly detected strain, consistent with previous studies, but a
      surprising variety of strains were identified in both collections. An eighth
      astrovirus type, HAstV-8, has been defined on the basis of the complete capsid
      protein gene sequence and was detected in both collections analysed in this
      study. Although HAstV-8 and HAstV-4 strains segregate into well resolved clades
      by analysis of sequences from the region encoding protein P2 (VP32), the pair
      wise distances between these types are less than those between strains of the
      other serotypes. In contrast, analysis of sequences from the region encoding
      protein P3 unambiguously resolve HAstV-4 and HAstV-8 strains, consistent with
      their classification as distinct serotypes. Overall, strains representing six of
      the eight serotypes were detected in two collections of samples from prospective
      studies of gastroenteritis in young children indicating that multiple astrovirus
      types are frequently co-circulating within communities.

PMID- 11444030
TI  - Enteric infections with coronaviruses and toroviruses.
AB  - Many enteric viruses are difficult or impossible to propagate in tissue culture.
      Coronaviruses and toroviruses are large, enveloped, plus-strand RNA viruses in
      the order Nidovirales that cause enteric disease in young pigs, cows, dogs, mice,
      cats and horses. Two different serogroups of mammalian coronaviruses cause
      frequent respiratory infections in humans, and coronaviruses and toroviruses have
      been implicated in human diarrhoeal disease by immunoelectron microscopy.
      However, there is as yet no consensus about the importance of these enveloped
      viruses in human diarrhoea, and little is known about their genetic variability.
      The large spike (S) glycoprotein is an important determinant of species
      specificity, tissue tropism and virulence of coronavirus infection. To infect
      enterocytes, both S glycoproteins and the viral envelope must resist degradation
      by proteases, low and high pH, and bile salts. One specific site on the S
      glycoprotein of bovine coronavirus must be cleaved by an intracellular protease
      or trypsin to activate viral infectivity and cell fusion. S glycoprotein binds to
      specific receptors on the apical membranes of enterocytes, and can undergo a
      temperature-dependent, receptor-mediated conformational change that leads to
      fusion of the viral envelope with host membranes to initiate infection. Analysing
      spike-receptor interactions may lead to new ways to propagate these enteric
      viruses as well as new strategies for development of novel antiviral drugs.

PMID- 11444031
TI  - Structural studies on gastroenteritis viruses.
AB  - There are many recent advances in our understanding of the structure-function
      relationships in rotavirus, a major pathogen of infantile gastroenteritis, and
      Norwalk virus, a causative agent of epidemic gastroenteritis in humans. Rotavirus
      is a large (1000 A) and complex icosahedral assembly formed by three concentric
      capsid layers that enclose the viral genome of 11 dsRNA segments. Because of its
      medical relevance, intriguing structural complexity, and several unique
      strategies in the morphogenesis and replication, this virus has been the subject
      of extensive biochemical, genetic and structural studies. Using a combination of
      electron cryomicroscopy and computer image processing together with atomic
      resolution X-ray structural information, we have been able to provide not only a
      better description of the rotavirus architecture, but also a better understanding
      of the structural basis of various biological functions such as trypsin-enhanced
      infectivity, virus assembly and the dynamic process of endogenous transcription.
      In contrast to rotavirus, Norwalk virus has a simple architecture with an
      icosahedral capsid made of 180 copies of a single protein. We have determined the
      structure of the Norwalk virus capsid to a resolution of 3.4 A using X-ray
      crystallographic techniques. These studies have provided valuable information on
      domain organization in the capsid protein, and residues that may be critical for
      dimerization, assembly, strain-specificity and antigenicity.

PMID- 11444032
TI  - Viruses causing diarrhoea in AIDS.
AB  - Opportunistic viral enteritis is an important gastrointestinal manifestation of
      HIV related disease. Cytomegalovirus (CMV) is a well established aetiological
      agent of disease in the gastrointestinal tract in this group. CMV enteritis may
      affect any region of the bowel, most commonly the colon. Diagnosis and management
      of these infections may be difficult. The role of other viruses in so-called
      'pathogen-negative' diarrhoea remains controversial. The clinical importance of
      HIV-specific enteropathy is probably limited. Several viruses including
      astrovirus, picobirnavirus, small round structured virus and rotavirus have been
      implicated HIV-related diarrhoea. In addition, adenovirus has been linked to
      persistent diarrhoea in patients with a characteristic adenovirus colitis. The
      spectrum of disease morbidity and mortality amongst HIV patients has altered
      dramatically since the wide spread use of highly active antiretroviral therapy
      (HAART). Opportunistic infections, including CMV infection of the
      gastrointestinal tract in patients with AIDS, have diminished greatly. AIDS
      patients with CMV are able successfully to discontinue anti-CMV treatment without
      disease reactivation and with a parallel reduction in CMV viraemia following the
      initiation of HAART.

PMID- 11444033
TI  - Treatment of gastrointestinal viruses.
AB  - The most common enteric viruses responsible for diarrhoea are rotavirus, enteric
      adenoviruses, caliciviruses including the Norwalk agent and astrovirus. These
      infections are usually mild to moderate in severity, self-limiting and of short
      duration and thus, specific antiviral therapy is not recommended. The standard
      management of these infections is restoration of fluid and electrolyte balance
      and then maintenance of hydration until the infection resolves. WHO oral
      rehydration therapy (ORT) was introduced about 30 years ago and has saved the
      lives of many infants and young children. During the last 10 years it has become
      evident that the efficacy of ORT can be increased by reducing the osmolality of
      the WHO oral rehydration solution (ORS) to produce a relatively hypotonic
      solution. Hypotonic ORS appears to be safe and effective in all forms of acute
      diarrhoea in childhood. Complex substrate ORS, which is also usually hypotonic,
      has been shown to have increased efficacy in cholera but not in other bacterial
      or viral diarrhoeas. Nevertheless, the scientific rationale for using rice or
      resistant starch as substrate in ORS is of physiological interest. Other
      treatments such as hyperimmune bovine colostrum, probiotics and antiviral agents
      are largely experimental and have not been introduced into routine clinical
      practice. Cytomegalovirus (CMV) infection of the gastrointestinal tract occurs
      mainly in the immunocompromised although it has been reported in immunocompetent
      individuals. CMV infects both the oesophagus and colon to produce oesophagitis,
      often with discrete ulcers, and colitis, respectively. Both conditions can be
      treated with ganciclovir or foscarnet. Failure to respond to monotherapy is an
      indication to use both agents concurrently.

PMID- 11444034
TI  - Early events of rotavirus infection: the search for the receptor(s).
AB  - The entry of rotaviruses into epithelial cells seems to be a multistep process.
      Infection competition experiments have suggested that at least three different
      interactions between the virus and cell surface molecules take place during the
      early events of infection, and glycolipids as well as glycoproteins have been
      suggested to be primary attachment receptors for rotaviruses. The infectivity of
      some rotavirus strains depends on the presence of sialic acid on the cell
      surface, however, it has been shown that this interaction is not essential, and
      it has been suggested that there exists a neuraminidase-resistant cell surface
      molecule with which most rotaviruses interact. The comparative characterization
      of the sialic acid-dependent rotavirus strain RRV (G3P5[3]), its neuraminidase
      resistant variant nar3, and the human rotavirus strain Wa (G1P1A[8]) has allowed
      us to show that alpha 2 beta 1 integrin is used by nar3 as its primary cell
      attachment site, and by RRV in a second interaction, subsequent to its initial
      contact with a sialic acid-containing cell receptor. We have also shown that
      integrin alpha V beta 3 is used by all three rotavirus strains as a co-receptor,
      subsequent to their initial attachment to the cell. We propose that the
      functional rotavirus receptor is a complex of several cell molecules most likely
      immersed in glycosphingolipid-enriched plasma membrane microdomains.

PMID- 11444035
TI  - Gastroenteritis viruses: an overview.
AB  - Acute gastroenteritis is among the most common illnesses of humankind, and its
      associated morbidity and mortality are greatest among those at the extremes of
      age, children and the elderly. In developing countries, gastroenteritis is a
      common cause of death in children < 5 years that can be linked to a wide variety
      of pathogens. In developed countries, while deaths from diarrhoea are less
      common, much illness leads to hospitalization or doctor visits. Much of the
      gastroenteritis in children is caused by viruses belonging to four distinct
      families--rotaviruses, caliciviruses, astroviruses and adenoviruses. Other
      viruses, such as the toroviruses, picobirnaviruses, picornavirus (the Aichi
      virus), and enterovirus 22, may play a role as well. Viral gastroenteritis occurs
      with two epidemiologic patterns, diarrhoea that is endemic in children and
      outbreaks that affect people of all ages. Viral diarrhoea in children is caused
      by group A rotaviruses, enteric adenoviruses, astroviruses and the caliciviruses;
      the illness affects all children worldwide in the first few years of life
      regardless of their level of hygiene, quality of water, food or sanitation, or
      type of behaviour. For all but perhaps the caliciviruses, these infections
      provide immunity from severe disease upon reinfection. Epidemic viral diarrhoea
      is caused primarily by the Norwalk-like virus genus of the caliciviruses. These
      viruses affect people of all ages, are often transmitted by faecally contaminated
      food or water, and are therefore subject to control by public health measures.
      The tremendous antigenic diversity of caliciviruses and short-lived immunity to
      infection permit repeated episodes throughout life. In the past decade, the
      molecular characterization of many of these gastroenteritis viruses has led to
      advances both in our understanding of the pathogens themselves and in development
      of a new generation of diagnostics. Application of these more sensitive methods
      to detect and characterize individual agents is just beginning, but has already
      opened up new avenues to reassess their disease burden, examine their molecular
      epidemiology, and consider new directions for their prevention and control
      through vaccination, improvements in food and water quality and sanitary
      practices.

PMID- 11444036
TI  - Rotavirus RNA replication and gene expression.
AB  - Rotavirus mRNAs are capped but non-polyadenylated and serve as templates for both
      the synthesis of viral proteins and the segmented dsRNA genome. Viral proteins
      involved in RNA replication include the RNA polymerase (VP1), the core scaffold
      protein (VP2) and the non-structural RNA-binding proteins (NSP2 and NSP5). VP2
      enhances dsRNA synthesis in vitro, possibly by forming platform structures on
      which VP1 functions. NSP2 octamers have NTPase and helix-destabilizing activity,
      and in conjunction with the phosphoprotein NSP5, are proposed to facilitate RNA
      packaging. The structure of the mRNA template contributes importantly to RNA
      replication. In particular, base-pairing between the 5' and 3'-ends of viral mRNA
      generates panhandle structures which promote minus-strand synthesis. For the
      group A rotaviruses, the 3'-consensus sequence, 5'-UGUGACC-3', which extends as a
      3'-tail from the panhandles, also contributes to efficient minus-strand
      synthesis. Besides containing cis-acting replication signals, the 3'-end of viral
      mRNAs contains information that stimulates gene expression in infected cells.
      Specifically, the last four nucleotides of the 3'-consensus sequence, 5'-GACC-3',
      operate as a virus-specific translation enhancer (3'TE) via a process thought to
      involve recognition of the element by NSP3. The NSP3-3'TE complex may mimic the
      function of complexes formed by eukaryotic poly(A)-tails and poly(A)-binding
      protein, thereby promoting more efficient translation of viral mRNAs.

PMID- 11444037
TI  - Pathogenesis of rotavirus gastroenteritis.
AB  - The outcome of intestinal infection with rotaviruses is more complex than
      initially appreciated, and it is affected by a complex interplay of host and
      viral factors. Rotaviruses infect intestinal enterocytes, and the early events in
      infection are mediated by virus-epithelial cell interactions. Diarrhoea may be
      caused by several mechanisms including (i) malabsorption that occurs secondary to
      the destruction of enterocytes, (ii) villus ischaemia and activation of the
      enteric nervous system that may be evoked by release of a vasoactive agent from
      infected epithelial cells in the absence of significant pathologic lesions or
      enterocyte damage, and (iii) intestinal secretion stimulated by the intracellular
      or extracellular action of the rotavirus non-structural protein, NSP4, a novel
      enterotoxin and secretory agonist with pleiotropic properties. New studies of
      rotavirus infection of polarized intestinal epithelial cells show that
      rotaviruses infect cells differently depending on whether or not they require
      sialic acid for initial binding, and infection alters epithelial cell functions.
      NSP4 also affects epithelial cell function and interactions. NSP4 (i) induces an
      age- and dose-dependent diarrhoeal response in young rodents that is similar to
      virus-induced disease, (ii) stimulates a Ca(2+)-dependent cell permeability where
      the secretory response is age-dependent, and (iii) alters epithelial cell
      integrity. Antibody to NSP4 protects mouse pups from diarrhoea induced by
      homotypic and heterotypic viruses. These data support a new mechanism of
      rotavirus-induced diarrhoea whereby a viral enterotoxin triggers a signal
      transduction pathway that alters epithelial cell permeability and chloride
      secretion. This new information about how a gastrointestinal virus causes disease
      demonstrates common pathogenic mechanisms for viral and bacterial pathogens not
      previously appreciated. These results also suggest new approaches to prevent or
      treat rotavirus-induced diarrhoea.

PMID- 11444039
TI  - Timing cell-cycle exit and differentiation in oligodendrocyte development.
AB  - During animal development many cells permanently stop dividing and terminally
      differentiate. For the most part, the mechanisms that control when the cells exit
      the cell cycle and differentiate are not known. We have been studying the
      mechanisms in the oligodendrocyte cell lineage. Studies of oligodendrocyte
      precursor cells (OPCs) in culture suggest that each OPC has a built-in timing
      mechanism that helps determine when the cell stops dividing and differentiates.
      This intrinsic timer consists of at least two components--a timing component,
      which measures elapsed time, and an effector component, which stops cell division
      and initiates differentiation at the appropriate time. The timer seems to involve
      both transcriptional and posttranscriptional mechanisms, with some proteins
      progressively increasing and others progressively decreasing over time.

PMID- 11444040
TI  - Splitting the chromosome: cutting the ties that bind sister chromatids.
AB  - In eukaryotic cells, replicated DNA molecules remain physically connected from
      their synthesis in S phase until they are separated during anaphase. This
      phenomenon, called sister chromatid cohesion, is essential for the temporal
      separation of DNA replication and mitosis and for the equal separation of the
      duplicated genome. Recent work has identified a number of chromosomal proteins
      required for cohesion. In this review we discuss how these proteins may connect
      sister chromatids and how they are removed from chromosomes to allow sister
      chromatid separation at the onset of anaphase.

PMID- 11444041
TI  - The cell cycle machinery and asymmetric cell division of neural progenitors in
      the Drosophila embryonic central nervous system.
AB  - Asymmetric cell divisions can be mediated by the preferential segregation of
      intrinsic cell fate determinants into one of two sibling daughters. In dividing
      Drosophila neural progenitors the apical-basal orientation of the mitotic
      spindle, the basal cortical localization of the cell fate determinants Numb
      and/or Prospero as well as the coordination of these events are mediated by
      several proteins which include Bazooka (Baz), Inscuteable (Insc) and Partner of
      Inscuteable (Pins) which localize as an apical cortical complex starting at
      interphase. Here I will summarize data which suggest that the formation of this
      apical complex involves two distinct steps: (1) during the initiation of apical
      complex formation in interphase neuroblasts, there appears to be a hierarchical
      relation amongst these components where Baz recruits Insc and Baz/Insc in turn
      recruit Pins to the apical cortex/stalk; (2) while in delaminated mitotic
      neuroblasts the maintenance of the apical cortical localization of these proteins
      is dependent on the presence of all three components. Moreover, we show that the
      maintenance of this apical protein complex is essential for the correct execution
      of asymmetric division. Finally, the localization of the various asymmetrically
      localized proteins shows cell cycle dependence; however, the involvement of the
      cell cycle regulator in asymmetric cell divisions has not been previously shown.
      Here we present evidence from ongoing experiments which suggest a requirement for
      the key cell cycle regulator cdc2 in asymmetric cell divisions.

PMID- 11444042
TI  - Spindle positioning during the asymmetric first cell division of Caenorhabditis
      elegans embryos.
AB  - Cell division during development in many cases generates daughter cells that
      differ not only in fate, but also in size. We investigate the mechanisms that
      ensure proper spindle positioning during such asymmetric divisions using the one
      cell stage Caenorhabditis elegans embryo as a model system. We utilized a UV
      laser microbeam as an in vivo microtubule-severing device to probe the forces
      driving spindle positioning. Our results indicate that extra-spindle pulling
      forces acting on the spindle poles dictate spindle position along the anterior
      posterior embryonic axis. Importantly, forces acting on the posterior spindle
      pole appear more extensive than those acting on the anterior one, thus explaining
      the overall posterior spindle displacement that leads to the asymmetric division
      of the wild-type one-cell stage embryo. In separate work, we analysed a locus
      called zyg-8, which plays a key role in ensuring proper spindle positioning. Our
      data show that zyg-8 is required to promote microtubule growth and/or stability
      during anaphase. We identified the molecular nature of the zyg-8 locus in the
      course of a large-scale RNAi-based functional genomics screen. ZYG-8 harbours two
      notable protein domains: a Ca2+/calmodulin-dependent kinase domain, and a domain
      related to doublecortin, a human microtubule-associated protein involved in
      neuronal migration.

PMID- 11444043
TI  - Growth factors controlling imaginal disc growth in Drosophila.
AB  - In the imaginal discs of Drosophila, contact-dependent cell interactions are
      important both for promoting cell proliferation and for limiting it at the end of
      the growth period. However, recent work indicates that diffusible growth factors
      are also important in regulating growth and proliferation. We have identified a
      family of five imaginal disc growth factors (IDGFs) by purifying mitogenic
      proteins that accumulate in conditioned medium during culture of imaginal disc
      cell lines. These proteins cooperate with insulin to stimulate not only
      proliferation, but also polarization and motility of imaginal disc cells. They
      are produced by the fat body and are probably active on a variety of peripheral
      tissues. The IDGFs are structurally related to chitinases, but they show an amino
      acid substitution that is known to abrogate catalytic activity and to transform
      chitinases into lectins. We suggest that these proteins act as endogenous
      mitogenic lectins and mediate nutritional effects on tissue growth, possibly by
      interacting with the insulin receptor pathway. Glycoproteins similar to the IDGFs
      are found in mammals and may constitute a novel class of growth factors and/or
      inflammatory cytokines.

PMID- 11444044
TI  - Imprinted genes and the coordination of fetal and postnatal growth in mammals.
AB  - A substantial proportion of genes that control fetal growth in placental mammals
      are imprinted. Imprinted genes can act in fetal tissues to regulate growth by
      cell proliferation, cell death and the make up of extracellular space. Imprinted
      growth-promoting genes such as Igf2 probably act predominantly in an endocrine
      fashion, thus coordinating organ growth with the growth of the organism. In
      overgrowth and growth deficiency syndromes, however, imprinted growth factors can
      act by more local mechanisms, resulting in disproportionate growth. In addition
      to controlling fetal growth directly and thereby determining the nutritional
      demand of the fetus, imprinted genes can also apparently limit the nutritional
      supply to the fetus through the placenta. Imprinted genes may also be involved in
      postnatal growth up to weaning.

PMID- 11444045
TI  - The temporal control of cell cycle and cell fate in Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans develops through two major phases: the first
      phase, embryogenesis, consists of a rapid series of cleavage cell divisions
      leading to morphogenesis of a first stage larva. The second phase is
      postembryonic development, which consists of developmentally regulated cell
      cycles that occur during the four larval stages leading to the adult. Precursor
      cells set aside during embryogenesis divide through stereotypical cell lineage
      patterns during the four larval stages to generate larval and adult structures.
      The precise timing of the postembryonic cell divisions is under strict control,
      in most cases with a developmentally regulated G1. In certain postembryonic cell
      lineages, various aspects of the cell division cycle, including cell cycle exit,
      or G1/S progression, are controlled by temporal regulatory genes of the
      heterochronic gene pathway. Heterochronic genes also control the timing of
      numerous other developmental events, indicating that this pathway functions to
      coordinate the schedule of cell division and cellular differentiation throughout
      the animal. Some choices of cell fate that occur in response to inductive or
      lateral signals are linked to cell cycle progression, suggesting that cell cycle
      phase can confer a critical period for developmental potential in certain cells.

PMID- 11444046
TI  - Responses to DNA damage in Xenopus: cell death or cell cycle arrest.
AB  - Xenopus embryos divide rapidly following fertilization. During this rapid period
      of cleavage, cell divisions are not sensitive to DNA replication or spindle
      assembly inhibition. Here, we have investigated the consequences of eliciting DNA
      damage in these embryos. We show that the rapid cell divisions are not affected
      by DNA damage. However, as the embryos reach the onset of gastrulation, they
      undergo rapid and synchronous apoptosis. We have investigated the regulation on
      this delayed apoptotic response to DNA damage. Next, we have reconstituted a DNA
      damage cell cycle checkpoint in vitro, demonstrating that all the checkpoint
      signalling components are present in the embryos but are not activated under the
      experimental conditions used to generate DNA damage in the embryo.

PMID- 11444047
TI  - Control of cell fate in plant meristems.
AB  - In contrast to animals, plants do not stop to initiate organs with the end of
      embryogenesis. Instead, most of the growth and development of higher plants will
      take place during later phases following germination of the seed. Plant
      development depends on the activity of two meristems, the root meristem and the
      shoot apical meristem (SAM), that are located at opposite ends of the plant
      embryo. These meristems serve as a source of pluripotent stem cells and, in case
      of the SAM, provide a centre for repetitive organ initiation. In order to
      maintain the SAM throughout plant life, the cells that are lost from the meristem
      through organ initiation and differentiation have to be replaced from the stem
      cell population. In this paper, we will discuss recent results indicating that
      the fate of stem cells in plant meristems is controlled by directional signalling
      systems.

PMID- 11444048
TI  - Pattern- and growth-linked cell cycles in Drosophila development.
AB  - During Drosophila development the cell cycle is subject to diverse regulatory
      inputs. In embryos, cells divide in stereotypic patterns that correspond to the
      cell fate map. There is little cell growth during this period, and cell
      proliferation is regulated at G2/M transitions by patterned transcription of the
      Cdk1-activator, Cdc25/String. The string locus senses pattern information via a >
      40 kb cis-regulatory region composed of many cell-type specific transcriptional
      enhancers. Later, in differentiated larval tissues, the cell cycle responds to
      nutrition via mechanisms that sense cellular growth. These larval cell cycles
      lack mitoses altogether, and are regulated at G/S transitions. Cells in
      developing imaginal discs exhibit a cycle that is regulated at both G1/S and G2/M
      transitions. G2/M progression in disc cells is regulated, as in the embryo, by
      string transcription and is thus influenced by the many transcription factors
      that interact with string's 'pattern-sensing' control region. G1/S progression in
      disc cells is controlled, at least in part, by factors that regulate cell growth
      such as Myc, Ras and phosphatidylinositol-3-kinase. Thus G1/S progression appears
      to be growth-coupled, much as in the larval endocycles. The dual control
      mechanism used by imaginal disc cells allows integration of diverse inputs which
      operate in both cell specification and cell metabolism.

PMID- 11444050
TI  - Cell cycle transitions in early Xenopus development.
AB  - Xenopus oocytes and embryos undergo two major maternally controlled cell-cycle
      transitions: oocyte maturation and the mid-blastula transition (MBT). During
      maturation, the essential order of events in the cell cycle is perturbed in that
      the M phases of Meiosis I and II occur consecutively without an intervening S
      phase. Use of U0126, a new potent inhibitor of MAPK kinase (MEK), shows that MAPK
      activation is essential to inhibit the anaphase-promoting complex and cyclin B
      degradation at the MI/MII transition. If MAPK is inactivated, cyclin B is
      degraded, S phase commences and meiotic spindles do not form. These events are
      restored in U0126-treated oocytes by a constitutively active form of the protein
      kinase p90Rsk. Thus all actions of MAPK during maturation are mediated solely by
      activation of p90Rsk. At the MBT, commencing with the 13th cleavage division,
      there are profound changes in the cell cycle. MBT events such as maternal cyclin
      E degradation and sensitivity to apoptosis are regulated by a developmental timer
      insensitive to inhibition of DNA, RNA or protein synthesis. Other events, such as
      zygotic transcription and the DNA replication checkpoint, are controlled by the
      nuclear:cytoplasmic ratio. Lengthening of the cell cycle at the MBT is caused by
      increased Tyr15 phosphorylation of Cdc2 resulting from degradation of the
      maternal phosphatase Cdc25A and continued expression of maternal Wee1. Ionizing
      radiation causes activation of a checkpoint mediating apoptosis when administered
      before but not after the MBT. Resistance to apoptosis is associated with
      increased p27Xic1, the relative fraction of Bcl-2 or Bax in pro- versus anti
      apoptotic complexes, and the activity of the protein kinase Akt.

PMID- 11444049
TI  - Regulation of the embryonic cell proliferation by Drosophila cyclin D and cyclin
      E complexes.
AB  - Cell proliferation during Drosophila development occurs in a well known spatial
      and temporal pattern which can readily be studied in vivo. The cells which form
      the larval epidermis exit from the cell division cycle during embryogenesis after
      the 16th round of mitosis when they enter for the first time into a G1/0 phase.
      We are interested in the mechanistic basis of this cell proliferation arrest. We
      have shown that the arrest requires the down-regulation of cyclin E/Cdk2 activity
      by inhibition of cyclin E expression and parallel activation of Dacapo/p27
      expression. In addition, up-regulation of Fizzy-related is observed and is
      required for inhibition of Cdk1 activity. Do these processes result from the down
      regulation of D-type cyclin/Cdk complexes? Extensive evidence from mammalian
      cells, and in particular from tumour cells has suggested that these complexes act
      as master regulators of cell proliferation upstream of cyclin E. Our genetic
      analyses indicate that Drosophila cyclin D/Cdk4, which interacts with the
      Drosophila Rb family member as expected, does not play an essential role in the
      regulation of cell proliferation.

PMID- 11444051
TI  - Cell cycle regulation in early mouse embryos.
AB  - For a long time it has been thought that the cell cycles of the early mouse
      embryo do not differ from the somatic cell cycle. They are long and are composed
      of classical G1, S, G2 and M phases and have functional checkpoint controls.
      However, a few characteristics observed during the earliest mitotic cleavage
      divisions suggest that the embryonic cell cycle could differ significantly from
      the somatic ones. Understanding these differences could have an important impact
      on our understanding of both general cell cycle mechanisms as well as the
      developmental programme of the early mouse embryo. Over the last few years our
      laboratories have undertaken a project focused on describing the differences in
      the first two cell cycles of the mouse embryo. We discuss here the results
      concerning (1) the way mouse oocytes switch from the meiotic to the mitotic cell
      cycle upon activation of development (inactivation of the cytostatic factor,
      CSF); (2) how the entry into the first and the second mitotic M phase is
      regulated (nucleus-independent activation of M phase-promoting factor, MPF); and
      (3) how the duration of the early embryonic mitoses is regulated. These data show
      that developmentally regulated phenomena are superimposed on and highly
      coordinated with the cell cycle machinery.

PMID- 11444052
TI  - Family support and acceptance, gay male identity formation, and psychological
      adjustment: a path model.
AB  - While heterosexist family undermining has been demonstrated to be a developmental
      risk factor in the life of persons with same-gender orientation, the issue of
      protective family factors is both controversial and relatively neglected. In this
      study of Israeli gay males (N = 114), we focused on the interrelations of family
      support, family acceptance and family knowledge of gay orientation, and gay male
      identity formation, and their effects on mental health and self-esteem. A path
      model was proposed based on the hypotheses that family support, family
      acceptance, family knowledge, and gay identity formation have an impact on
      psychological adjustment, and that family support has an effect on gay identity
      formation that is mediated by family acceptance. The assessment of gay identity
      formation was based on an established stage model that was streamlined for cross
      cultural practice by defining three basic processes of same-gender identity
      formation: self-definition, self-acceptance, and disclosure (Elizur & Mintzer,
      2001). The testing of our conceptual path model demonstrated an excellent fit
      with the data. An alternative model that hypothesized effects of gay male
      identity on family acceptance and family knowledge did not fit the data.
      Interpreting these results, we propose that the main effect of family
      support/acceptance on gay identity is related to the process of disclosure, and
      that both general family support and family acceptance of same-gender orientation
      play a significant role in the psychological adjustment of gay men.

PMID- 11444053
TI  - Attributions and emotional reactions to the identity disclosure ("coming out") of
      a homosexual child.
AB  - This study examined factors that contribute to parental rejection of gay and
      lesbian youth. College students (N = 356) were asked to imagine being the parent
      of an adolescent son who recently disclosed that he was gay. Consistent with
      study hypotheses and based on attribution and moral affect theory, results of
      regression analyses indicated that greater perceptions of control over
      homosexuality, higher proneness to experience shame, and lower proneness to
      experience guilt were associated with increasing negative reactions toward an
      imagined homosexual child. Also in line with study hypotheses, greater
      willingness to offer help to the hypothetical child was predicted by lower
      perceptions of control over homosexuality, less intensely unfavorable emotional
      reactions, less proneness to experience guilt, and greater reported likelihood of
      experiencing affection toward him. Theoretical and clinical implications of this
      research are discussed.

PMID- 11444054
TI  - Mother and child perceptions of child functioning: relationship to maternal
      distress.
AB  - The relationship between maternal distress and mother's reports of psychosocial
      problems in their children has been well-documented. However, relatively little
      research has investigated the relationship between maternal and family distress
      and young children's perception of their own functioning. Using a brief
      questionnaire designed for use with children, data were collected from 166
      mothers and their children aged 5-12 years. Children provided information about
      their own daily functioning, and mothers provided information about their own,
      their child's, and their family's psychosocial functioning. Findings indicated
      that while children generally agreed with the reports of their mothers, children
      of distressed mothers self-reported better daily functioning than their mothers
      did. Distressed mothers tended globally to report negatively about themselves,
      their child, and their family. The present findings suggest that when assessing
      mothers or children, the reports of children should be considered as well as the
      reports of mothers.

PMID- 11444055
TI  - Triangulation and adolescent development in the U.S. and Japan.
AB  - Using an indirect measure of family structure, relationships between parents and
      adolescents were studied in 99 U. S. and 60 Japanese families. As two-person
      relationships tend toward instability under stress, a third person may be drawn
      in to stabilize the system. Parents, for example, may avoid the tension in the
      marital relationship by focusing together on an adolescent's problem, or pull the
      adolescent into a coalition with one parent. Either way the parents are said to
      have "triangled" the adolescent. In this study, a relationship is found between
      parents avoiding tension in their own relationship and their tendency to triangle
      an adolescent. Triangled daughters, in both cultures, had lower scores on ego
      development, supporting the hypothesis that such patterns can be detrimental to
      the adolescent's personal development. The discussion includes comments on cross
      cultural research.

PMID- 11444056
TI  - Comparing the second-order factor structure of the Family Environment Scale
      across husbands' and wives' perceptions of their family environment.
AB  - The Family Environment Scale (Moos & Moos, 1986) is one of the most widely used
      environmental measures in clinical and family research. Clinicians and
      researchers often use the FES for comparing spouses' perceptions of their family
      environment, under the assumption that the underlying structure of the FES is the
      same for husbands and wives. However, no studies have actually compared the
      structure of the FES across spouse responses to the FES. Additionally, a review
      of the literature generally suggests a lack of consensus regarding the factor
      structure of the FES. Using confirmatory factor analyses, we examined whether the
      second-order factor structures of the FES, as identified in the literature, were
      consistent across spouses' perceptions of their family environment. Husbands and
      wives in 130 nonclinical families responded to Form R of the FES. The findings
      supported the two-factor solution presented by Fowler (1981) and by Boake and
      Salmon (1983), and did not differ across responses by husbands and wives. In
      contrast, responses by husbands and wives to the FES could not be modeled using
      the three-factor solutions presented by Moos and Moos (1986) and by others. The
      importance of using a measure that is structurally the same across different
      groups of respondents is discussed.

PMID- 11444057
TI  - The impact of psychiatric diagnosis and family system relationship on problems
      identified by families coping with a mentally ill member.
AB  - The purpose of this study was to explore how psychiatric diagnosis and family
      relationships relate to problems identified by participants in three one-day
      public family psychoeducation workshops for families with a member with a serious
      mental illness. Workshop participants generated lists of problems they had faced,
      which were coded into eleven categories. Logistic regression models predicting
      listing of categories were developed based on ill member (diagnosis, sex,
      treatment compliance) and family member (sex, age, relationship to the ill
      member) characteristics. For models predicting content category from ill member
      characteristics, only denial/noncompliance and interpersonal/social categories
      were significantly predictive as dependent variables. For models predicting
      content categories from family member characteristics, only the
      resources/benefits model was predictive. The significant findings, in conjunction
      with the important negative results, suggest implications for further development
      of family intervention models. Building on previous research, groups composed of
      families coping with more than a single diagnosis and including a variety of
      family member relationships have the potential to reach consensus on curriculum
      topics.

PMID- 11444058
TI  - Translation and validation of the Spanish version of the RELATE questionnaire
      using a modified serial approach for cross-cultural translation.
AB  - This article describes the initial translation and validation of the Spanish
      version of the RELATionshhip Evaluation (RELATE) questionnaire with a sample of
      monolingual English speakers (n = 78), a sample of monolingual Spanish speakers
      (n = 18), and two samples of Spanish/English Bilinguals (n = 27 and n = 34).
      Cross-cultural and cross-language equivalence of the Spanish version of RELATE to
      the original English version were assessed using a Modified Serial Approach (MSA)
      for instrument translation. Face and content validity of the Spanish RELATE were
      established. Test-retest reliability indices obtained with the translated version
      among the monolingual and bilingual Spanish speaking groups were consistently
      equivalent to, and in some cases higher than, the baseline reliability obtained
      with the monolingual English speaking group. Applications of the Spanish version
      of RELATE and use of the MSA for researchers and practitioners are presented.

PMID- 11444059
TI  - Conflict and healing in family experience of second-generation emigrants from
      India living in North America.
AB  - In this article, I describe a study that generates a substantive theory of
      healing from the conflict experienced by second-generation emigrants from India
      living in North America. Qualitative methodology, specifically, the Grounded
      Theory method of data analysis and theory building, was used. Literature
      elucidating the differences between North American and Indian cultural values was
      used as a basis for exploration. Results suggest that cultural conflict stems
      from areas such as education and success, pressure from parents to maintain
      traditional cultural values, family bonds and lack of boundaries, parental
      control and abuse, and dating and marriage. The results of the conflict are
      discussed by participants in terms of loneliness and pain, lying, rebellion, or
      acceptance of cultural values. The factors that mediate the conflict and that
      determine the degree to which participants rebel or accept the cultural values
      seem to be linked to the approval and acceptance individuals received from their
      family or community and their level of self-esteem. Finally, I discuss how
      individuals can heal from the conflict. Methods of healing include communication
      with and education for parents, therapy in the areas of anger, resentment, and
      self-esteem, and developing an alternative support system, which may include
      other second-generation individuals.

PMID- 11444060
TI  - Let's end the bleaching controversy.

PMID- 11444061
TI  - About informed consent.

PMID- 11444062
TI  - Smile on! MDA launches new TV ads, hot new Web site!

PMID- 11444063
TI  - The dental Web: using it to your advantage.

PMID- 11444064
TI  - MDA position paper on vital tooth bleaching.

PMID- 11444065
TI  - Palatogingival developmental groove.

PMID- 11444066
TI  - Fixed partial dentures with an all-ceramic system: a case report.
AB  - The success of a dental prosthesis is judged according to function, comfort,
      phonetics, and esthetics. The purpose of a treatment is to come as close as
      possible to replicating the natural state. For anterior fixed partial dentures,
      the all-ceramic system IPS Empress 2 offers light transmission and reflection
      comparable to that of natural teeth, provided that the pink esthetics are
      optimized in the preprosthetic treatment phase. In this case report, a laboratory
      made provisional was placed after extraction of an anterior tooth. Six months
      later, preprosthetic periodontal surgery was carried out to enhance gingival
      harmony. The design of the post and core, preparation, and cementation are
      important parameters for the success of all-ceramic restorations.

PMID- 11444067
TI  - The "flexible augmented flange technique" for fabricating complete denture record
      bases.
AB  - A technique for fabricating complete denture record bases that features flanges
      augmented with resilient liner is reintroduced and recommended. It is coined the
      "flexible augmented flange technique." The technique takes advantage of the
      elastic properties of tissue conditioner, available anatomic undercuts in
      definitive casts, and the rigidity of record base resin to create stable,
      retentive, well-fitting, and comfortable record bases that minimally abrade
      casts. Tissue conditioner, which strongly bonds to the intaglio surface of record
      base flanges, replaces blockout wax to form augmented flanges with flexible inner
      sections that are sufficiently elastic to engage and then release from undercuts.
      The flexibility of the inner section of the flanges permits atraumatic insertion
      and removal from a patient's mouth, despite overall record base rigidity.
      Accurate, verifiable, maxillomandibular jaw relation records can be obtained with
      the flexible augmented flange technique.

PMID- 11444068
TI  - Effects of drugs and systemic factors on orthodontic treatment.
AB  - Orthodontic tooth movement and bone remodeling activity are dependent on systemic
      factors such as nutritional factors, metabolic bone diseases, age, and use of
      drugs. Therefore, a comprehensive review of the effects of these factors on
      orthodontic tooth movement is attempted in this article. Systemic hormones such
      as estrogen, androgen, and calcitonin are associated with an increase in bone
      mineral content, bone mass, and a decrease in the rate of bone resorption.
      Consequently, they could delay orthodontic tooth movement. On the contrary,
      thyroid hormones and corticosteroids might be involved in a more rapid
      orthodontic tooth movement during orthodontic therapy and have a less stable
      orthodontic result. Drugs such as bisphosphonates, vitamin D metabolites, and
      fluorides can probably cause a reduction of tooth movement after the orthodontic
      force is applied. Nonsteroidal anti-inflammatory drugs have also been shown to
      reduce bone resorption. Long-term administration of these drugs may therefore
      delay the necessary bone response to respective tooth-borne pressure and should
      not be administered for long periods of time to patients undergoing orthodontic
      tooth movement. Attention has also been focused on the effects of prostaglandins
      and leukotrienes in orthodontic tooth movement. It seems that they might have
      future clinical applications that could result in enhanced tooth movement. The
      use of the above drugs should be considered by every dentist in evaluating the
      treatment time and in planning treatment when tooth movement is attempted.

PMID- 11444069
TI  - Prevalence and distribution of dentin hypersensitivity and plaque in a dental
      hospital population.
AB  - OBJECTIVE: Dentin hypersensitivity (DH) is a commonly reported dental problem.
      Conflicting results on the degree of plaque accumulation at sites with DH have
      been reported. Therefore, the prevalence and distribution of DH and dental plaque
      were studied in a dental hospital population. METHOD AND MATERIALS: A total of
      302 adult patients were examined for the presence of DH by means of a
      questionnaire and intraoral examinations. Oral hygiene was measured by Silness
      and Loe's Plaque Index. RESULTS: The overall prevalence of DH was 52.6%.
      Significantly more women complained of DH than men. Dentin hypersensitivity and
      Plaque Index scores were found to be significantly higher in the older age group
      than in younger groups. Spearman's correlation test revealed no correlation for
      DH with plaque. About half of the patients reported DH for a duration of within 1
      month, while 23% claimed that their DH lasted for 1 to 5 years. Approximately 64%
      of the patients reported that sensitivity did not interfere with their ability to
      eat, drink, or brush their teeth, with slight to moderate discomfort, while 11.4%
      had a severe concern, thereby avoiding these activities most of the time. Of the
      patients, 17% received professional treatment, while 25% used desensitizing
      toothpastes. Dentin hypersensitivity was found in all types of teeth, but was
      most common in first molars and mandibular incisors and canines. CONCLUSION:
      Because there was no correlation for DH with plaque, a careful assessment of the
      etiologic or predisposing factors must be considered before attempting the
      management of patients complaining of hypersensitive teeth.

PMID- 11444070
TI  - Use of tissue conditioner in pediatric dentistry: a clinical case report.
AB  - This report intends to show the use of tissue conditioners on esthetic and
      functional removable partial dentures, placed by the technique of direct relining
      immediately after surgery to protect the surgical wound and aid the
      cicatrization.

PMID- 11444071
TI  - Use of dental implants in children: a literature review.
AB  - The aim of this literature review is to discuss the use of dental implants in
      growing patients and the influence of maxillary and mandibular skeletal and
      dental growth on the stability of those implants. It is recommended to wait for
      the completion of dental and skeletal growth, except for severe cases of
      ectodermal dysplasia.

PMID- 11444072
TI  - Effect of solvent and rewetting time on dentin adhesion.
AB  - OBJECTIVE: The purpose of this in vitro study was to determine the influence of
      solvent and rewetting time on microtensile dentin bond strengths of four dentin
      adhesives. METHOD AND MATERIALS: Sixty human molar specimens were divided into
      four dentin adhesive treatment groups: (1) a water-based total-etch dentin
      adhesive, EBS Multi; (2) an ethanol-based total-etch adhesive, Excite; (3) an
      acetone-based total-etch adhesive, Prime & Bond NT; and (4) an ethanol- and water
      based total-etch adhesive, Single Bond. For each dentin adhesive, three specimens
      were assigned to five dentin moisture conditions. Specimens were tested in the
      tensile mode. RESULTS: When adhesives were applied to moist dentin, bond
      strengths varied from 26.2 MPa for Prime & Bond NT to 29.5 MPa for Single Bond
      without any statistical differences. When applied to dentin that had been dried
      for 15 seconds, Prime & Bond NT and Excite resulted in the lowest mean bond
      strengths, but they were statistically similar to each other (7.9 and 8.3 MPa,
      respectively). Single Bond resulted in a mean bond strength of 12.7 MPa, which
      was significantly lower than that of EBS Multi (24.1 MPa). For the latter, all
      mean bond strengths were statistically similar when some amount of moisture was
      present on the surface. For the other three adhesives, mean bond strengths
      returned to the range obtained on moist dentin only when dentin was rewet for 30
      seconds. CONCLUSION: Bond strengths upon rewetting depend on the type of solvent
      in the bonding system, and rewetting time.

PMID- 11444073
TI  - Marginal adaptation of amalgam and resin composite restorations in Class II
      conservative preparations.
AB  - OBJECTIVE: The purpose of this study was to compare and contrast the performance,
      in terms of marginal adaptation, of a non-gamma-2 amalgam alloy with a compact
      filled light-cured composite in the restoration of Class II preparations of
      conservative design. METHOD AND MATERIALS: Fifty recently extracted teeth were
      selected for the study. The teeth were restored with either a non-gamma-2 amalgam
      alloy, Dispersalloy, or a compact-filled resin composite, Z100, using standard
      techniques. The marginal adaptation of the restorative materials to the proximal
      surface outline form of each preparation was assessed at magnification x30.
      RESULTS: Highly significant differences were demonstrated in the mean percentages
      of perfect margins in all 3 segments of the proximal boxes of the restorations
      with the resin composite performing significantly better than the amalgam. The
      percentages of marginal fissuring were significantly higher in the amalgam
      restorations, except at the cervical margin, where the incidence of fissuring was
      almost the same for the amalgam and resin composite restorations. The resin
      composite restorations had significantly fewer underfilled margins than the
      amalgam restorations. CONCLUSION: In the conservative Class II preparations, the
      amalgam restorations were of poor quality with respect to marginal adaptation,
      compared with the resin composite restorations. It is suggested that the use of
      amalgam as a control in a clinical evaluation of resin composite restorations in
      conservative preparations cannot be justified, because it is apparently not
      possible to compare restorations of equivalent initial quality.

PMID- 11444074
TI  - The outcome of teeth with periapical periodontitis treated with nonsurgical
      endodontic treatment: a computerized morphometric study.
AB  - OBJECTIVES: This study investigated the prognosis for successful endodontic
      treatment and the correlation between the size of the periapical lesion, the
      quality of the root canal treatment, and the type of coronal restoration. METHOD
      AND MATERIALS: Periapical radiographs of 319 teeth with periapical periodontitis
      were studied. The area of each lesion was measured before treatment and 1 to 12
      years after completion of the endodontic treatment. The measurements were
      performed using computerized morphometry. RESULTS: In 65.2% of the teeth, the
      size of the lesion decreased, while in 34.8% of teeth, there was an increase.
      Lesions larger than 10 mm2 had a greater tendency for healing. CONCLUSION: No
      significant correlation was found between the quality of root canal treatment,
      the type of the coronal restoration, and the success rate of the endodontic
      treatment.

PMID- 11444075
TI  - Surface hardness of light-activated resin composites cured by two different
      visible-light sources: an in vitro study.
AB  - OBJECTIVE: Microhardness values of upper and lower surfaces of disk specimens of
      3 commercially available resin composites were compared and cured using both the
      traditional halogen source and a plasma arc lamp. METHOD AND MATERIALS: Twenty
      samples of each of the resin composites were cured in nylon washers. Ten samples
      of each composite were cured using the appropriate halogen lamp protocol, and 10
      samples of each were cured using the plasma lamp protocol. Surface microhardness
      measurements were carried out using a calibrated Vickers indenter on both top and
      bottom surfaces after 7 days of storage in air at 20 degrees C. Statistical
      analysis of the data was carried out using a commercial statistical package. The
      data for top and bottom surfaces were analyzed separately using a repeated
      measures analysis of variance (ANOVA). RESULTS: Lamp, composite, and the
      interaction between lamp and composite were significant in determining the
      results for both top and bottom surfaces of the disk-shaped specimens. The plasma
      lamp yielded lower hardness values for all surfaces compared with the halogen
      source, but the size of the difference depended on the composite. CONCLUSION:
      Caution must be exercised in the plasma irradiation of resin composites as a
      curing method due to the possibility of reduced surface microhardness values that
      may reflect a reduced percent conversion of monomer to polymer.

PMID- 11444076
TI  - Abrasiveness of an air-powder polishing system on root surfaces in vitro.
AB  - OBJECTIVE: The purpose of this study was to evaluate the abrasiveness of a new
      air polisher on root surfaces. METHOD AND MATERIALS: Fifty extracted human teeth
      were air polished for 5 seconds. RESULTS: All root surfaces showed a circular
      defect visible with the naked eye. Scanning electron microscope examination
      showed smooth crater walls and a few open dentin tubules, but most seemed to be
      obliterated. Laser profilometry of the exposed areas revealed defects with an
      average depth of 484 microns, whereas the unexposed root surfaces showed
      irregularities with an average depth of 323 microns. The depths of the abraded
      areas were evaluated in relation to the values for the unexposed surfaces, and an
      average depth of 161 microns was found. The difference between the exposed and
      unexposed surfaces was statistically significant. CONCLUSION: The present study
      indicates that the air polisher has a strong abrading effect on exposed root
      surfaces and should therefore be used with caution on patients with gingival
      retractions.

PMID- 11444077
TI  - In vitro microleakage of composite restorations after nonvital bleaching.
AB  - OBJECTIVE: After bleaching treatment, esthetic restorations often need to be
      replaced due to color changes. Some papers have shown alterations in the bond of
      adhesive restorations to bleached teeth. The purpose of this study was to
      evaluate tooth and resin composite adhesion when submitted to nonvital dental
      bleaching. METHOD AND MATERIALS: One hundred and twenty bovine teeth were
      assigned to 3 groups (n = 40); paste of sodium perborate and water; 37% carbamide
      peroxide gel; and no bleaching (control). After 3 weeks of continuous bleaching
      treatment, standardized Class V cavities were prepared at the cementoenamel
      junction and restored with Single Bond adhesive system and Z100 resin composite.
      The samples were thermocycled 1,500 times (5 +/- 1/55 +/- 1 degrees C) with a 1
      minute dwell time. Then, they were immersed in a 2% methylene blue solution (pH
      7) for 4 hours, sectioned, and analyzed by stereomicroscopy. Microleakage
      analyses were done, using scores from 0 to 4, considering leakage on the incisal
      wall (enamel) and the cervical wall (dentin). Data were analyzed by Kruskal
      Wallis and Mann-Whitney tests (alpha = 0.05). RESULTS: The results showed that
      sodium perborate and carbamide peroxide gel significantly increase the
      microleakage in Class V resin composite restorations to dentin but not to enamel
      margins. CONCLUSION: The risk of microleakage in dentin margins is increased soon
      after bleaching treatment.

PMID- 11444078
TI  - Osteoid osteoma.

PMID- 11444079
TI  - Initiation of osteoporosis treatment after bone mineral density testing.
AB  - The aim of the study was to describe initiation of osteoporosis drug therapy
      after bone mineral density (BMD) testing and to determine any association with
      BMD test results obtained, physician factors, or both. The setting was the Kaiser
      Foundation Health Plan (KFHP), a large health maintenance organization (HMO) in
      Northern California. Data were collected from bone densitometry centers at four
      KFHP medical centers sites in Sacramento, San Rafael, Fresno, and Oakland. We
      identified 17,290 women aged > or = 45 years who had BMD testing between January
      1, 1997 and June 30, 1999. After excluding those for whom any osteoporosis drugs
      were prescribed in the year before testing, 8020 women were available for
      analysis. Using logistic regression, we examined the association between BMD
      diagnosis (i.e., osteoporosis or osteopenia versus normal) and initiation of drug
      therapy, for osteoporosis (including hormone replacement therapy (HRT),
      alendronate, etidronate, raloxifene and calcitonin) within 6 months after the
      test. Among the 8020 women, 1934 (24%) filled a prescription for an osteoporosis
      drug within 6 months after BMD testing. Compared with women who had a normal BMD
      test result, women diagnosed with osteopenia were nearly 4 times more likely (OR
      = 3.7; CI = 3.0-4.4), and women diagnosed with osteoporosis were 15 times more
      likely (OR = 15.0; CI = 12.5-18.1), to fill a prescription for an osteoporosis
      drug within 6 months after BMD testing. Women with high exposure to
      corticosteroid agents were twice as likely (OR = 2.1; CI = 1.7-2.7) to start
      osteoporosis drug therapy compared with women who were not similarly exposed;
      women diagnosed with recent osteoporotic fractures were 50% more likely (OR =
      1.5; CI = 1.2-1.9) to begin therapy than women without such fractures. Despite
      the strong association between BMD and initiating treatment, nearly half the
      osteoporotic women did not initiate treatment. In addition, we found that age
      strongly influenced choice of osteoporotic drug. Compared with osteoporotic women
      aged 45-54 years, women aged 55-64 years who started drug therapy were 40% more
      likely (OR = 1.4; CI = 1.0-2.2) and women aged > or = 65 years were twice as
      likely (OR = 2.0; CI = 1.4-2.8) to start non-HRT drugs. BMD test results
      indicating osteoporosis were thus strongly associated with increased likelihood
      of beginning drug therapy, and half of such women initiated therapy. Drug
      initiation was also associated with other factors, including age, use of
      corticosteroid agents, recent fracture, and physician characteristics. However,
      these factors showed much weaker associations than those found for BMD. Health
      care providers must consider whether test results will influence treatment
      decisions, and our data indicate that results of BMD testing do influence
      management decisions regarding osteoporosis drug use for women.

PMID- 11444080
TI  - Bone mineral density and body composition in ulcerative colitis: a six-year
      follow-up.
AB  - Reduced bone mineral density (BMD) has been reported in ulcerative colitis (UC),
      but there are no data concerning body composition (fat and lean mass) in such
      patients. We used whole body dual-energy X-ray absorptiometry (Hologic QDR 1000
      W) at baseline and after 6 years of follow-up to study bone density, and fat and
      lean mass in 43 outpatients with mild UC (21 men, mean age 36 years, range 21-57
      years, and 22 women, mean age 35 years, range 23-45 years at baseline; disease
      extent: 2 proctitis, 18 proctosigmoiditis, 8 left colitis, 5 substantial colitis,
      10 pancolitis; mean disease duration 8 years, range 2-18 years; no
      hospitalization; few relapses during the follow-up) and 111 healthy volunteers
      matched by sex, age and body mass index. There were 5 drop-outs. We observed no
      significant difference in BMD, or fat and lean mass between the male patients and
      controls at baseline or after 6 years. The total lean mass (Z-score = -3.2, p =
      0.001) and trunk lean mass (Z-score = -2.01, p = 0.03) of the female patients
      were lower than those of the controls at baseline, whereas their limb lean mass
      was higher at both the beginning and the end of the study (Z-score = 2.14, p =
      0.03; Z-score = 2.8, p = 0.004, respectively). At baseline there was a
      significant negative correlation between lifetime steroid intake (enteral and
      parenteral) and lumbar spine BMD, obtained as whole body subregion (r = -0.53, p
      = 0.0006). After 6 years there was a significant negative correlation in women
      between whole body and lumbar spine BMD and both steroid intake (r = -0.53, p =
      0.01; and r = -0.62, p = 0.003) and the number of relapses (r = -0.49, p = 0.02;
      and r = -0.44, p = 0.05). Mild UC thus does not represent a risk factor for
      osteopenia per se. The differences in lean mass between the female patients and
      controls do not seem to be clinically relevant.

PMID- 11444081
TI  - Regular physical exercise and bone mineral density: a four-year controlled
      randomized trial in middle-aged men. The DNASCO study.
AB  - The aim of the study was to investigate the effects of regular aerobic exercise
      training on bone mineral density (BMD) in middle-aged men. A population based
      sample of 140 men (53-62 years) was randomly assigned into the exercise and
      reference groups. BMD and apparent volumetric BMD (BMDvol) of the proximal femur
      and lumbar spine (dual-energy X-ray absorptiometry, DXA) and anthropomorphic
      measurements were performed at the randomization and 2 and up to 4 years later.
      The participation rate was 97% and 94% at the second and third BMD measurements,
      respectively. As another indication of excellent adherence and compliance, the
      cardiorespiratory fitness (aerobic threshold) increased by 13% in the exercise
      group. The 2% decrease in the reference group is regarded as an age-related
      change in cardiorespiratory fitness. Regardless of the group, there was no
      association between the increase in aerobic threshold and change in BMD. In the
      entire group, age-related bone loss was seen in the femoral neck BMD and BMDvol
      (p < 0.01). BMD and BMDvol values increased with age in L2-L4 (p < 0.004). An
      increased rate of bone loss at the femoral neck was observed in men with a low
      energy-adjusted calcium intake (p = 0.003). Men who increased their alcohol
      intake during the intervention showed a decrease in the rate of bone loss at the
      femoral neck (p = 0.040). A decrease in body height associated with decreased
      total femoral BMD (r = 0.19, p = 0.04) and the change in body height was a
      predictor of bone loss in the femoral neck (beta = 0.201). Long-term regular
      aerobic physical activity in middle-aged men had no effect on the age-related
      loss of femoral BMD. On the other hand, possible structural alterations, which
      are also essential for the mechanical strength of bone, can not be detected by
      the DXA measurements used in this study. The increase seen in lumbar BMD reflects
      age-related changes in the spine, thus making it an unreliable site for BMD
      follow-up in men.

PMID- 11444082
TI  - Cost-effectiveness of preventing hip fracture in the general female population.
AB  - The aims of this study were to determine whether treatments that reduce the
      incidence of hip fracture might be used in the general female population rather
      than screening or case-finding strategies. Cost-effectiveness, measured as cost
      per quality-adjusted life-year (QALY) gained using threshold values for cost
      effectiveness of $20,000 or $30,000/QALY gained, was assessed during and after
      treatment using a computer simulation model applied to the female population of
      Sweden. The base case assumed a 5-year intervention that reduced the risk of hip
      fracture by 35% during the treatment period, and an effect that reversed to the
      pretreatment risk during the next 5 years. Sensitivity analyses included the
      effects of age, different treatment costs and effectiveness. Cost-effectiveness
      was critically dependent upon the age and costs of intervention. Reasonable cost
      effectiveness was shown even with relatively high intervention costs for women at
      average risk at the age of 84 years or more. For the cheapest interventions
      ($63/year) cost-effectiveness could be found from the age of 53 years. Variations
      in effectiveness (15-50% risk reduction) had marked effects on the age that
      treatment was worthwhile. We conclude that segments of the apparently healthy
      population could be advantaged by treatment if efficacy were supported by
      randomized controlled studies.

PMID- 11444083
TI  - Skeletal site bone mineral density heterogeneity in women and men.
AB  - The heterogeneity of skeletal bone mineral density, measured on a single dual
      energy X-ray absorptiometer, was examined in a large cohort of 7050 women and 702
      men referred for investigation of osteoporosis. The men were significantly older
      (64.8 +/- 13.2 vs 60.2 +/- 11.5 years) and had an increased prevalence of
      nontraumatic fractures (ODR: 2.18; 95% CI: 1.82-2.61). The detection rate
      (sensitivity) for any osteoporosis (spine or hip) in women was 87.1% and 45.1%
      when assessed at the anteroposterior (AP) spine and femoral neck respectively.
      The corresponding osteoporosis detection rate in men was 69.3% and 67.5% at the
      AP spine and femoral neck respectively. Age-related AP spine degenerative changes
      increased significantly and at a similar rate for both women and men.
      Misclassification, that is osteoporosis (T-score < -2.5) at one site and normal
      (T-score > -1) bone mass at the other, was low in both genders (< 4.5%), but 3.1
      (95% CI: 2.1-4.6) times more likely in women when the diagnosis was based on the
      femoral neck compared with the AP spine. Our findings suggest that there are
      significant age- and gender-related bone mineral density differences between the
      spine and hip skeletal sites which have to be considered if only one site is
      selected for investigation.

PMID- 11444084
TI  - Vertebral deformities and low bone mineral density in adults with cystic
      fibrosis: a cross-sectional study.
AB  - Patients with cystic fibrosis (CF) have low bone mineral density (BMD). The
      clinical relevance of this is not clearly established. The aim of this study was
      to determine the prevalence of low BMD and vertebral deformities in CF adults
      with varied disease severity. One hundred and seven patients (58 men) aged 18-60
      years underwent dual-energy X-ray absorptiometry scanning of the lumbar spine and
      hip, radiology of the spine and biochemical studies. Thirty-eight percent had a Z
      score of < -1, with 13% having Z-scores < -2. Seventeen percent had evidence of
      vertebral deformity on radiography, mostly in the thoracic spine. Thirty-five
      percent reported past fractures, of which 9% were rib fractures. Percent
      predicted forced expiratory volume in 1 second (FEV1) and the amount of daily
      physical activity were positively related to BMD. The number of intravenous
      antibiotic courses in the previous 5 years was negatively related to BMD.
      Patients with a history of rib fracture and CF-related diabetes had significantly
      lower femoral neck BMD (p < 0.02). The median serum 25-hydroxyvitamin D was 28
      nmol/l, with 36% of patients having levels below 25 nmol/l despite vitamin D
      supplementation. Forty-four percent had raised levels of urinary pyridinium
      crosslinks (NTx). In conclusion, fragility fractures and hypovitaminosis D occur
      commonly in adult patients with CF. Low BMD occurs in patients with more severe
      disease and significantly relates to FEV1, infective exacerbations and daily
      energy expended in physical activity.

PMID- 11444085
TI  - Maintenance of body weight, physical activity and calcium intake helps preserve
      bone mass in elderly women.
AB  - This prospective study focused on lifestyle factors and weight maintenance that
      may modulate the rate of bone loss at the weight-bearing proximal femur and non
      weight-bearing distal radius in elderly women. Altogether 128 women of 134
      subjects participated in this study with a mean follow-up time 3.9 years (range
      2.9-5.3 years). The initially 60- to 65-year-old subjects were originally
      selected by their level of physical activity [high (PA+) and low (PA-)] and
      calcium intake [high (Ca+) and low (Ca-)], and the original groups were
      maintained in this study. Physical fitness and bone mineral content (BMC)
      decreased significantly at a similar rate in all four study groups without any
      statistically significant between-group difference. The mean change in the muscle
      strength of leg extensors was -3.3% (95% CI -5% to -1.5%) at follow-up when
      including all individuals. The leg extension strength was still 9.2% (95% CI 2.7%
      to 16.1%) better in the PA+ groups compared with PA- groups at follow-up. The
      mean change in the forearm flexion strength was -14% (95% CI -16.5% to -11.3%) at
      follow-up with no difference in the strength level between PA+ and PA- groups.
      The mean change in the estimated oxygen uptake was -3.4% (95% CI -5.6% to -1.1%)
      at follow-up. The PA+ groups were still fitter, the between-group difference in
      the estimated oxygen uptake being 11.9% (95% CI 4.8% to 19.5%). The mean changes
      in BMC at follow-up were -2.1% (95% CI -3.0% to -1.2%) at the femoral neck, -1.9%
      (95% CI -3.2% to -0.5%) at the trochanter, and -12.4% (95% CI -15.4% to -9.4%) at
      the distal radius, indicating mean annual losses of 0.6% (95% CI 0.3% to 0.8%),
      0.5% (95% CI 0.1% to 0.8%), and 3.2% (95% CI 2.4% to 4.0%), respectively.
      Decreased body weight was associated with higher bone loss in all measured bone
      sites. High calcium intake and better preservation of physical fitness were
      associated with a smaller decrease in femoral neck BMC.

PMID- 11444086
TI  - The effect of fluvastatin on parameters of bone remodeling.
AB  - Statins decrease the hepatic biosynthesis of cholesterol, and reduce the
      incidence of myocardial infarction in women who have already experienced a
      myocardial infarction. Statins also reduce the risk of atherosclerosis in
      diabetic patients, but it is unknown whether they influence the glucose
      tolerance. It has further been suggested that they may influence bone metabolism.
      Vitamin C is an antioxidant and it decreases serum cholesterol moderately.
      Antioxidants may also have other metabolic effects, but these are insufficiently
      studied. The aim of the present study was to investigate the metabolic effects of
      the cholesterol-lowering agent fluvastatin and the antioxidant vitamin C. Sixty
      eight elderly, postmenopausal women with osteoporosis and mild
      hypercholesterolemia were randomly assigned to 12 weeks open treatment with
      either fluvastatin (40 mg daily) + 500 mg vitamin C (n = 45) or vitamin C only (n
      = 23). We measured biochemical markers of bone formation (serum osteocalcin and
      total alkaline phosphatase) and bone resorption (serum and urinary CTX),
      parameters related to diabetes and serum lipids and lipoproteins. Fluvastatin in
      combination with vitamin C had no effect on bone formation markers. We found a
      weak decrease in parameters of bone resorption, which was significant from
      baseline, but not different between the two groups. There were no significant
      effects on any of the other markers of either fluvastatin or vitamin C. The lipid
      lowering effect of fluvastatin was confirmed with a decrease of 20% and 30% in
      serum total cholesterol and LDL-cholesterol, respectively. We conclude that
      fluvastatin given in clinically relevant doses has no influence on parameters of
      bone remodeling. Other statins remain to be investigated.

PMID- 11444087
TI  - Withdrawal of hormone replacement therapy is associated with significant
      vertebral bone loss in postmenopausal women.
AB  - This study aimed to assess the changes in vertebral bone mineral density (BMD)
      after cessation of hormone replacement therapy (HRT) in postmenopausal women who
      had been treated on a long-term basis. Fifty healthy postmenopausal women who had
      been followed both during the course of HRT and after cessation of treatment in
      our menopause clinic were included in this study. All women had started HRT
      within the first 3 years after the postmenopause and had received HRT (either 1.5
      mg/day of 17 beta-estradiol given percutaneously or 50 micrograms/day of 17 beta
      estradiol given as a transdermal patch, combined in all women with natural
      progesterone or a 19-norprogesterone derivative) for a mean 5 +/- 2.4 years. In
      all women, vertebral BMD was assessed during the course of HRT up to the last 6
      months before estrogen withdrawal, then at least once within the first 18 months
      after cessation of treatment. Of the initial population, 30 women were
      additionally reviewed later on and up to 8 years after cessation of treatment
      (mean duration of follow-up for the whole population: 3.9 +/- 1.7 years). Rates
      of changes in vertebral BMD were compared with those determined in a group of
      healthy untreated women who had been followed within the first years of
      postmenopause during the same time period as the study population. In the study
      group, bone loss was found to accelerate within the first 2 years after HRT
      withdrawal and the annual rate of loss was identical to that which occurs within
      the first 2 years of postmenopause in untreated women (-1.64% +/- 1.3% vs -1.52
      +/- 0.9%, NS). Beyond this first 2-year time period, the annual rate of bone loss
      decreased as a function of time following cessation of treatment, as was observed
      following the menopause in untreated women (between 3 and 5 years: -0.83% + 1.35%
      in the study group vs -0.70% +/- 0.8% in the control group, NS). On average, 3
      years after cessation of HRT mean vertebral BMD when expressed as a Z-score was
      significantly higher (-0.13 vs -0.89, p < 0.01) than at baseline, before HRT was
      started, which suggested a lasting beneficial effect on bone mass. However, even
      though our findings do not support the hypothesis that bone loss might continue
      to be accelerated several years after cessation of treatment we cannot fully
      address the question as to whether any residual benefit on bone mass over a
      longer period of time may be observed. In conclusion, the pattern of bone loss
      observed after cessation of estrogen therapy was found to be comparable to that
      which occurs in younger women within the first years after the menopause. Such a
      pattern needs to be kept in mind when the decision to stop HRT is taken,
      especially in women who were given HRT to prevent osteoporosis. The issue of
      assessing their risk of fracture several years after cessation of treatment thus
      needs to be addressed.

PMID- 11444088
TI  - Clinical performance of a highly portable, scanning calcaneal ultrasonometer.
AB  - The aim of this study was to establish a normative database, assess precision,
      and evaluate the ability to identify women with low bone mass and to discriminate
      women with fracture from those without for a highly portable, scanning calcaneal
      ultrasonometer: the QUS-2. Fourteen hundred and one Caucasian women were
      recruited for the study. Among them were 794 healthy women 25-84 years of age
      evenly distributed per 10-year period to establish a normative database. Of
      these, 171 aged 25-34 years were defined as the young normal group for the
      purpose of T-score determination. Precision was assessed within 1 day (short
      term) and over a 16-week period (long-term) in 79 women aged 25-84 years. Five
      hundred twenty-eight women ranging from 50 to 84 years of age with or without
      prevalent fractures of the spine, hip or forearm were measured to compare the QUS
      2 with bone mineral density (BMD) of the hip and spine. Mean calcaneal broadband
      ultrasound attenuation (BUA) was constant in healthy women from 25 to 54 years of
      age and decreased with increasing age thereafter. Short-term precision, with and
      without repositioning of the heel, and long-term precision yielded comparable
      results (BUA SDs of 2.1-2.4 dB/MHz, coefficients of variations (CVs) of 2.5
      2.9%). Calcaneal BUA was significantly correlated with BMD of the total hip (TH),
      femoral neck (FN) and lumbar spine (LS) in 698 women (r = 0.6-0.7, all p <
      0.0001). A similar relationship was observed for LS BMD compared with either TH
      or FN BMD (r = 0.7, p < 0.0001). Prevalence of osteoporosis in our population
      (WHO criteria) was 20%, 17%, 21%, and 24% for BUA, BMD of the TH, FN and LS,
      respectively. Age-adjusted values for a 1 SD reduction in calcaneal BUA and TH
      and FN BMD predicted prevalent fractures of the spine, forearm, and hip with
      significant (p < 0.05) odds ratios of 2.3, 2.0 and 2.1, respectively. Areas under
      the receiver operating characteristic curves for age-adjusted bone mass values
      predicting prevalent fracture were 0.62 for BUA, 0.59 for TH BMD, 0.60 for FN
      BMD, and 0.57 for LS BMD; all statistically equivalent. We conclude that the QUS
      2 calcaneal ultrasonometer exhibits reproducible clinical performance that is
      similar to BMD of the spine and hip in identifying women with low bone mass and
      discriminating women with fracture from those without.

PMID- 11444089
TI  - Ultrasound velocity and cortical bone characteristics in vivo.
AB  - Axial transmission of ultrasound along cortical bone may reflect a combination of
      material and structural properties of long bone cortices. The goal of this study
      was to determine the association of speed of sound (SOS) with cortical density
      (CoD), cortical wall thickness (CWT), and total cortical area (CoA). Quantitative
      ultrasound (QUS) and peripheral quantitative computed tomography (pQCT) were used
      to measure the above variables in the distal third of radius and the midshaft of
      tibia in 51 postmenopausal women aged 62 to 71 years. Univariate regression
      analysis showed that the site-specific CoD accounted for 34% of the variability
      in the radial SOS and 29% of that in the tibial SOS (p < 0.001 both). SOS was
      only moderately associated with radial CWT (R2 = 0.14, p < 0.05) and CoA (R2 =
      0.12, p < 0.05), but not with tibial CWT nor CoA. After controlling for CoD,
      these dimension-related associations disappeared. Stepwise multiple regression
      analysis showed that CoD was the only significant determinant of radial SOS
      (adjusted R2 = 0.31), whereas for tibia, not only CoD but also the years since
      menopause were associated with SOS (adjusted R2 = 0.41). In conclusion, out of
      the studied macroscopic cortical variables, CoD (an apparent surrogate for
      material properties of bone) was the only determinant of SOS measured in vivo at
      radial and tibial shafts. The key question that still needs to be answered is
      whether the SOS information obtained from the peripheral long bone cortical
      shafts can be translated to describe the mechanical competence and quality of
      clinically pertinent bones (e.g. proximal femur) of a given individual.

PMID- 11444090
TI  - Genetic variation in bone mineral density and calcaneal ultrasound: a study of
      the influence of menopause using female twins.
AB  - The aim of the study was to determine whether the genetic variance in bone
      mineral density (BMD) and calcaneal ultrasound differs in pre- and postmenopausal
      women and to establish whether the genes operating before the menopause are the
      same as those after the menopause. Twins aged 18-75 years were recruited from the
      St Thomas' UK Adult Twin Registry. Quantitative model fitting techniques were
      used to test for differences in genetic influences in pre- and postmenopausal
      twins of several BMD sites and calcaneal ultrasound measures accounting for age.
      BMD and heel ultrasound variables were measured in 2490 female twins: 360
      monozygotic pairs and 885 dizygotic pairs. The heritability in the group overall
      ranged from 19% to 76%. A significant increase in total variance was seen for
      most BMD sites after the menopause. The proportion of total variance explained by
      genetic influence was higher premenopausally at all sites except the femoral
      neck. For example, the genetic proportion of total variance for spine BMD was 88%
      premenopausally and 77% postmenopausally. In contrast there was no significant
      difference in total variance of ultrasound measures with menopause. There was no
      indication that traits are influenced by different genes before and after
      menopause. This study demonstrates that genetic and environmental influences
      differ significantly in pre- and postmenopausal groups for BMD, but not for
      calcaneal ultrasound. The total variance in BMD is greater postmenopausally, but
      there is evidence that the same genes are involved. These data stress the
      importance of accounting for menopause-gene interactions in the genetic analysis
      of data on osteoporosis.

PMID- 11444091
TI  - Ultrasound measurements at the proximal phalanges in male patients with psoriatic
      arthritis.
AB  - Bone ultrasound parameters at the proximal phalanges of the hands were measured
      in 55 male patients with psoriatic arthritis (PA) (39 with peripheral radiologic
      involvement and 16 with axial involvement), comparing the findings with those in
      16 rheumatoid arthritis (RA) patients, 20 ankylosing spondylitis (AS) patients
      and 55 age- and sex-matched normal controls. Mean values of amplitude-dependent
      speed of sound (Ad-SoS) and ultrasound bone profile score (UBPS) were
      significantly lower in RA (p < 0.001 and p < 1 x 10(-5)) and PA (p < 0.03 and p <
      1 x 10(-6)) patients than in controls, while there was no statistically
      significant difference between AS patients and healthy subjects. Ultrasound
      parameters showed a significant negative correlation with age in all groups. In
      each patient group ultrasound values were unrelated either to disease duration or
      to inflammatory indices such as erythrocyte sedimentation rate and C-reactive
      protein. Moreover no significant differences were observed between ultrasound
      parameters of the dominant and the nondominant hand. PA patients with and without
      axial radiologic changes did not show any differences in ultrasound parameters.
      However, PA subjects with peripheral involvement only had significantly higher Ad
      SoS (p < 0.04) and UBPS (p < 0.04) values than RA patients. PA patients with
      axial lesions had significantly lower (p < 0.04 and p < 0.01) ultrasound values
      than AS patients. These findings suggest that PA ultrasound techniques performed
      at the peripheral level are of value to speculate on bone involvement, although
      we think that ultrasound measurements cannot yet be recommended for monitoring
      bone involvement in these patients.

PMID- 11444092
TI  - The burden of osteoporotic fractures: a method for setting intervention
      thresholds.
AB  - The aim of this study was to assess the relationship between morbidity from hip
      fracture and that from other osteoporotic fractures by age and sex based on the
      population of Sweden. Osteoporotic fractures were designated as those associated
      with low bone mineral density (BMD) and those that increased in incidence with
      age after the age of 50 years. Severity of fractures was weighted according to
      their morbidity using utility values based on those derived by the National
      Osteoporosis Foundation. Morbidity from fractures other than hip fracture was
      converted to hip fracture equivalents according to their disutility weights.
      Excess morbidity was 3.34 and 4.75 in men and women at the age of 50 years, i.e.
      the morbidity associated with osteoporotic fractures was 3-5 times that accounted
      for by hip fracture. Excess morbidity decreased with age to approximately 1.25
      between the ages of 85 and 89 years. On the assumption that the age- and sex
      specific pattern of fractures due to osteoporosis is similar in different
      communities, the computation of excess morbidity can be utilized to determine the
      total morbidity from osteoporotic fractures from knowledge of hip fracture rates
      alone. Such data can be used to weight probabilities of hip fracture in different
      countries in order to take into account the morbidity from fractures other than
      hip fracture, and to modify intervention thresholds based on hip fracture risk
      alone. If, for example, a 10-year probability of hip fracture of 10% was
      considered an intervention threshold, this would be exceeded in women with
      osteoporosis aged 65 years and more, but when weighted for other osteoporotic
      fractures would be exceeded in all women (and men) with osteoporosis.

PMID- 11444093
TI  - Oxidative stress: cause or consequence of hypertension.

PMID- 11444094
TI  - Protection against oxidative stress by nitroxides.

PMID- 11444095
TI  - Cytotoxicity related to oxidative and nitrosative stress by nitric oxide.

PMID- 11444096
TI  - Raf-1 protein kinase, signal transduction, and targeted intervention of radiation
      response.

PMID- 11444097
TI  - In vivo protection against gamma-irradiation with 5-androstenediol.

PMID- 11444098
TI  - Chelated metal ions for therapeutic and diagnostic applications.
AB  - Use of radiolabeled monoclonal antibodies (mAb's) that localize and bind to
      malignant cells continues to be an attractive mechanism for targeting and
      delivering either an imagable isotope, be it a y-emitter or B(+)-emitter, or a
      particle emitter such as a B(-)-emitter or an a-emitter for therapeutic
      applications.

PMID- 11444099
TI  - A critical review of atypical cerebellum-type Creutzfeldt-Jakob disease: its
      relationship to "new variant" CJD and bovine spongiform encephalopathy.
AB  - Shortly after the appearance of bovine spongiform encephalopathy (BSE),
      Creutzfeldt-Jakob disease (CJD) was identified in young patients with
      nonclassical presentation such as difficulty in balancing and ataxia. The
      classical CJD in older patients starts with dementia. To distinguish between the
      two types, CJD in young persons has been termed "new variant" (nvCJD). The
      distinguishing features of classical CJD include initial presentation with
      dementia, confluent spongiform changes are very unusual in the cerebellum, and
      PrP plaques are rarely observed. For nvCJD, initially, difficulty with balancing
      and ataxia occurs, confluent spongiform changes are seen in the cerebellum, and a
      large number of PrP plaques are seen. The icelandic observation of sheep scrapie
      revealed a predominantly ataxic form of scrapie, termed Type II, rather than the
      itchy form termed Type I. Both types have been known to exist in Europe. Since
      the clinical signs of Type II scrapie in sheep with trembling and ataxia are
      similar to those seen in BSE and nvCJD, this suggests that Type II is the cause
      of BSE and nvCJD. Over 8 years, from 1989 to 1996, I examined the clinical
      histories of 33 CJD cases aged between the ages of 18 and 84. Six under the age
      of 40 and 15 over the age of 40 had leading clinical features such as difficulty
      in balancing and ataxia similar to those seen in the young cases classified as
      "nvCJD." Brains were examined from the six of 15 cases over the age of 40, which
      revealed similar pathology to that seen in young patients classified as "nvCJD."
      These findings suggest that all age groups are susceptible to the strain of the
      agent derived from BSE cattle.

PMID- 11444100
TI  - Lingering doubts about spongiform encephalopathy and Creutzfeldt-Jakob disease.
AB  - Bovine spongiform encephalopathy (BSE) is an infectious disease and has been
      transmitted orally to many other animals, including humans. There is clear
      evidence of maternal transmission, although disagreement on the source of the BSE
      agent remains. The current theories link the origin of BSE to common scrapie in
      sheep. Twenty different strains of the scrapie agent have been isolated from
      sheep. A search of the literature indicates two distinct clinical syndromes in
      sheep, both of which have been called scrapie. I have designated these Type I
      (the common type), which exhibits itchiness and lose their wool, and Type II,
      which exhibits trembling and ataxia. Sheep inoculated with BSE develop Type II
      scrapie and they exhibit trembling. When cattle or mink are injected with the
      Type I strain, only a few will develop a clinical disease. By contrast, no
      clinical disease has so far been shown in cattle or mink by feeding them with
      Type I-infected sheep brains. However, either by injecting or feeding with the
      BSE strain, 100% of calves and mink develop the clinical disease. Evidence
      suggests that Type II is the cause of BSE. Identical clinical signs of Type II
      trembling are found in kuru and many of the recent cases of Creutzfeldt-Jakob
      disease. The BSE agent has caused spongiform encephalopathies (SEs) in domestic
      cats, tigers, and in some species of ruminants in zoos. The nature of the BSE
      agent remains unchanged when passaged through a range of species, irrespective of
      their genetic make up, demonstrating that variations in the host PrP gene are not
      a major factor in the susceptibility to the BSE agent. Since more than 85 zoo
      animals of many species have been diagnosed with SEs, from these studies it seems
      reasonable to conclude that the BSE agent can infect almost all mammalian
      species, including humans. For eradication of BSE and to reduce the risk of
      infection to humans, the development of a vaccine against BSE is suggested. Such
      a possibility should be fully explored.

PMID- 11444101
TI  - Corneal epithelial wound healing.
AB  - One of the important functions of the cornea is to maintain normal vision by
      refracting light onto the lens and retina. This property is dependent in part on
      the ability of the corneal epithelium to undergo continuous renewal. Epithelial
      renewal is essential because it enables this tissue to act as a barrier that
      protects the corneal interior from becoming infected by noxious environmental
      agents. Furthermore, the smooth optical properties of the corneal epithelial
      surface are sustained through this renewal process. The rate of renewal is
      dependent on a highly integrated balance between the processes of corneal
      epithelial proliferation, differentiation, and cell death. One experimental
      approach to characterize these three aspects of the renewal process has been to
      study the kinetics and dynamics of corneal re-epithelialization in a wound
      healing model. This effort has employed in vivo and in vitro studies. From such
      studies it is evident that the appropriate integration and coordination of
      corneal epithelial proliferation, adhesion, migration, and cell demise is
      dependent on the actions of a myriad of cytokines. Our goal here is to provide an
      overview into how these mediators and environmental factors elicit control of
      cellular proliferation, adhesion, migration, and apoptosis. To this end we review
      the pertinent literature dealing with the receptor and the cell signaling events
      that are responsible for mediating cytokine control of corneal epithelial
      renewal. It is our hope that a better appreciation can be obtained about the
      complexity of the control processes that are responsible for assuring continuous
      corneal epithelial renewal in health and disease.

PMID- 11444102
TI  - Copper control as an antiangiogenic anticancer therapy: lessons from treating
      Wilson's disease.
AB  - The search for new anticopper drugs for Wilson's disease is culminating in two
      excellent new drugs: zinc for maintenance therapy and tetrathiomolybdate (TM) for
      initial therapy. Both are effective and nontoxic. TM is a very potent, fast
      acting new anticopper drug and its properties may be useful well beyond Wilson's
      disease. Angiogenesis (new blood vessel growth) is required for tumor growth, and
      a sufficient level of copper appears to be required for angiogenesis. We
      hypothesize that there is a "window" to which the copper level can be reduced
      that inhibits angiogenesis in tumors, but does not interfere with vital cellular
      functions of copper. Using TM therapy, this approach has worked to slow or
      stabilize tumor growth in several animal tumor models, and preliminary results
      are also very encouraging in human patients with a variety of advanced and
      metastatic malignancies. A hypothesis is advanced that copper availability has
      played a fundamental role in growth regulation throughout evolution and that is
      the reason that so many angiogenic promoters appear to be dependent upon copper
      levels.

PMID- 11444103
TI  - Ontogenic regulation of components of ileal bile acid absorption.
AB  - The apical sodium-dependent bile acid cotransporter (ASBT) and the ileal bile
      acid binding protein (IBABP) are two components of ileal bile acid absorption.
      During the third postnatal week of the rat, there is a dramatic increase in ASBT
      and IBABP expression. The goals of this study were to examine the role of
      hormones on the ontogenic expression of ASBT mRNA and the role of weaning for
      both ASBT and IBABP mRNA. Administration of various doses of dexamethasone during
      the second postnatal week induced ASBT mRNA levels, and this effect was
      significantly increased with concomitant thyroxine treatment. Early weaning and
      weaning prevention were utilized to investigate the influence of dietary factors.
      ASBT and IBABP mRNA levels were significantly elevated by early weaning and were
      decreased by weaning prevention compared with littermate controls. Thus,
      glucocorticoids and thyroxine appear to play a role in the ontogenic expression
      of ASBT mRNA and weaning appears to participate in both ASBT and IBABP
      expression.

PMID- 11444104
TI  - Transplantation of normal islets into the portal vein of Otsuka Long Evans
      Tokushima Fatty rats prevents diabetic progression.
AB  - To investigate the long-term effects of normal pancreatic islet transplantation
      on progression of obese type 2 diabetes mellitus (DM), 1500 normal islets (per
      rat) from Wistar King A rats at 8 weeks of age were transplanted into the liver
      through the portal vein of Otsuka Long Evans Tokushima Fatty (OLETF) rats, an
      animal model of obese type 2 DM, at 12 weeks of age. Body weight in the
      transplanted OLETF (IT) rats 8 and 28 weeks after islet transplantation did not
      differ from that in the corresponding sham-operated (SO) rats, but was greater
      than that in lean littermates (LETO rats; P < 0.05 for each group). In the early
      phase, 8 weeks after transplantation, rats in both IT and SO groups were
      normoglycemic, but hyperinsulinemic (P < 0.05 for each compared with LETO rats),
      probably resulting from increased body weight. In the late phase, 28 weeks after
      transplantation, hyperglycemia in the IT group was greatly attenuated compared
      with the SO group (P < 0.05), but hyperinsulinemia remained in both the IT and
      the SO groups compared with that in the LETO group (P < 0.05 for each).
      Immunohistochemical studies demonstrated that hypertrophic and fibrotic changes
      in pancreatic islets, together with mesangial proliferation of the glomerular
      matrix, an indicator for diabetic nephropathy, were attenuated predominantly in
      the IT group at the late phase after transplantation compared with those in the
      corresponding phase of the SO group. Islet transplantation into the liver of
      OLETF rats thus prevented further progression of obese type 2 DM. A possible
      mechanism is that islet transplantation may prevent development of hyperglycemia
      by improving abnormal hepatic glucose metabolism and consequently insulin
      resistance, which may lead to blockade of a vicious cycle between advancing
      damage to pancreatic islet cells and increased demand for insulin secretion, thus
      sparing original pancreatic cells from exhaustion induced by increased demand for
      insulin secretion.

PMID- 11444105
TI  - Regulation of PECAM-1 in endothelial cells during cell growth and migration.
AB  - Endothelial cells (EC) that form the inner lining of blood vessels remain
      quiescent in the normal adult vasculature except during angiogenesis and
      reendothelialization, which result in EC proliferation and migration. EC placed
      in culture at subconfluent density also undergo cell multiplication and movement.
      This report demonstrates that whereas in confluent EC in a compact monolayer, the
      EC-EC adhesion molecule platelet-endothelial cell adhesion molecule-1 (PECAM-1)
      is strongly expressed at cell borders, little or no PECAM-1 immunostaining is
      detected in sparse or migrating cultured EC. Consistent with this observation,
      steady-state PECAM-1 mRNA expression was much lower in subconfluent EC than in
      confluent EC. The absence of PECAM-1 expression in sparse EC appeared not to be
      linked to ability to proliferate, since PECAM-1 expression remained low even in
      the presence of nitric oxide (NO) or mitomycin C, agents that inhibit EC growth.
      However, another growth-inhibitory agent, TGF-beta 1, did not alter PECAM-1
      staining. Based on these observations, it is hypothesized that cell-associated
      mechanical forces underlying cell tensegrity regulate PECAM-1 expression.

PMID- 11444106
TI  - Acute pancreatitis signals activation of apoptosis-associated and survival genes
      in mice.
AB  - In experimental models of acute pancreatitis (AP), acinar cell death occurs by
      both necrosis and programmed cell death or apoptosis. Apoptosis is an active form
      of cell death associated with a tightly regulated expression of gene products
      that are either pro- or antiapoptotic. The aim of this study was to characterize
      pancreatic mRNA levels by Northern blotting analysis of apoptosis-associated
      genes used during the course of cerulein-induced AP in mice. Histone H3 mRNA
      levels were also examined as an indicator of cell proliferation. Acinar cell
      apoptosis was confirmed histologically. The findings show that AP modifies
      pancreatic mRNA levels of both pro- and antiapoptotic genes simultaneously.
      Pancreatic bclXL, bax, and p53 mRNA levels increased significantly in a temporal
      fashion during induction of AP. Pancreatic bcl-2 mRNA levels were unchanged
      during AP. Pancreatic mRNA levels of insulin-like growth factor-1 (IGF-1), a
      mitogen and cell survival factor, and its receptor (IGF-1R) also increased in a
      temporal fashion during induction of AP. In summary, this study indicates that
      acinar cell death during cerulein-induced AP in mice can occur by the apoptotic
      pathway. Since factors promoting and antagonistic for cell survival are activated
      simultaneously, regulation of acinar cell survival appears complex and dynamic
      during AP.

PMID- 11444107
TI  - GnRH and gonadotropin release is decreased in chronic nitric oxide deficiency.
AB  - Nitric oxide synthetase (NOS), the conversion enzyme for nitric oxide (NO) is
      localized in the anterior pituitary of female rats, particularly in gonadotrophs
      and folliculo-stellate cells, suggesting that NO regulates the release of
      luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior
      pituitary. The focus of this study was to determine the effect of chronic NO
      deficiency on the subsequent pituitary release of LH and FSH in vitro and the
      hypothalamic immunoexpression of GnRH in vivo. NO deficiency was induced by
      adding the NOS inhibitor, N-nitro-L-arginine (L-NNA, 0.6 g/L) to the drinking
      water of female Wistar rats. After 8 weeks, the animals were euthanized, the
      pituitaries were removed, and they were incubated in vitro. Pituitaries were
      perfused for 4 hr in the presence of pulsatile gonadotropin release hormone
      (GnRH, 500 ng/pulse) every 30 min. S-Nitroso-L-acetyl penicillamine (SNAP, an NO
      donor, 0.1 mM) or L-nitro-argine methyl ester (L-NAME, a NOS inhibitor, 0.1 mM)
      was added to the media and perfusate samples were collected at 10-min intervals.
      LH and FSH levels in the perfusate were measured by double antibody
      radioimmunoassays. Pituitaries from the NO-deficient rats had a significantly
      smaller GnRH-stimulated release of LH and FSH compared with proestrous control
      rats. The addition of S-NAP to the perfusate resulted in decreased LH and FSH
      secretion in the control group, but increased LH secretion in the NO-deficient
      group. The addition of L-NAME to the perfusate suppressed LH secretion from
      control pituitaries, but not in pituitaries from NO-deficient animals.
      Immunohistochemistry of brain slices demonstrated that NO-deficient rats had a
      large qualitative decrease of GnRH in the median eminence compared with their
      controls. This decrease was particularly evident in the external capillary plexus
      of the median eminence. We concluded that chronic NO deficiency is associated
      with a decreased GnRH in neurosecretory terminals in the external capillary layer
      of the median eminence, accompanied by a decrease in LH and FSH release from the
      pituitaries.

PMID- 11444108
TI  - Melatonin attenuates estradiol-induced oxidative damage to DNA: relevance for
      cancer prevention.
AB  - Estrogens exert pro-oxidative effects and have been shown to damage DNA,
      potentially leading to cancer. Melatonin is a well-known antioxidant, free
      radical scavenger, and oncostatic agent. Changes in the levels of 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxodGuo), an index of DNA damage, and the levels of
      malondialdehyde + 4-hydroxyalkenals, an index of lipid peroxidation, were
      measured in kidneys, liver, and testes from hamsters treated with E2 (75 mg/kg
      body wt) and were collected 3 or 5 hr later. Other animals were treated with
      melatonin (15 mg/kg body wt, 30 min before and 120 min after E2 treatment) or
      were given both compounds. Additionally, lipid peroxidation was measured in liver
      homogenates exposed to ferrous sulfate (15 microM) in vitro. E2 treatment caused
      an increase in 8-oxodGuo levels in kidneys collected 5 hr after E2
      administration, and in liver 3 hr after estrogen treatment. Melatonin completely
      prevented E2-induced DNA damage in both organs. Melatonin alone or when given
      with E2 and examined 3 hr later decreased the base level of 8-oxodGuo in testes.
      A tendency for a reduction in in vivo lipid peroxidation was observed after
      treatment of hamsters with either melatonin, E2, or both compounds, with a
      statistically significant decrease being measured in the liver following E2
      administration. In vitro exposure to iron significantly enhanced lipid
      peroxidation in hepatic homogenates from untreated, melatonin-treated, or E2
      injected hamsters; in the hepatic homogenates of hamsters given both E2 and
      melatonin, ferrous sulfate failed to augment lipid peroxidation. Our results
      confirm the dual actions of estrogens relative to oxidative damage, i.e.,
      estrogen increases oxidative destruction of DNA while reducing lipid
      peroxidation. Melatonin had antioxidative actions in reducing oxidative damage to
      both DNA and to membrane lipids. Melatonin completely prevented the damaging
      action of E2 on DNA and synergized with the steroid to reduce lipid peroxidation.

PMID- 11444109
TI  - Bronchoscopy. Year 2001 and beyond.
AB  - The current revolution in technology, imaging, and information processing will be
      of major influence on bronchoscopy within the next two decades. Clinicians will
      be able to visualize structures in vivo that up to now only the pathologist could
      see. Clinicians will reach anatomic structures that are inaccessible by the
      bronchoscope, yet treat diseases that are still the domain of surgeons, medical
      oncologists, and radiotherapists. Clinicians will be able to communicate online
      worldwide, improving standards of patient care, teaching, and finally even
      perform interventional procedures by way of networks. Because of the exponential
      growth of sciences like nanotechnology and biotechnology, these changes will come
      very rapidly. The new quality of these intelligent instruments will demand a new
      ideological and ethical discourse on the future of science in general.

PMID- 11444110
TI  - Role of bronchoscopy in modern medical intensive care unit.
AB  - This article gives a broad overview of the increasingly important applications of
      bronchoscopy, flexible (FOB) and rigid (RB), in a modern medical intensive care
      unit. Special emphasis is made to bronchoscopy use in mechanically ventilated
      patients. Therapies such as endobronchial stenting and Nd:YAG laser are being
      used to improve respiratory failure and facilitate weaning from mechanical
      ventilation. Practical applications of recent advancements in technology
      (endobronchial stenting, laser therapy, and so forth), the increasing use of
      rigid bronchoscopy, and the new generation of flexible bronchoscopes like battery
      bronchoscopes, and ultra-thin bronchoscopes, are also discussed. The risks,
      potential benefits, complications, and suggested technique of performing
      bronchoscopy in mechanically ventilated patients are reviewed.

PMID- 11444111
TI  - Flexible bronchoscopy in nosocomial pneumonia.
AB  - In this article, an overview on the diagnostic performances of bronchoscopic
      techniques for the diagnosis of nosocomial pneumonia is given with special
      emphasis on the inherent problems of the methodology of validation applied to
      different studies. The current evidence about the importance of bronchoscopic
      techniques for the outcome is reviewed. It is outlined that future prospects of
      bronchoscopic investigations mainly include the evaluation of its role in the
      reassessment of the patient with pneumonia not responding to the initial
      antimicrobial treatment.

PMID- 11444112
TI  - The flexible bronchoscope. A tool for anesthesiologists.
AB  - Fiberoptic intubation is the technique of choice in management of a difficult
      intubation. It should be a first choice, not a last resort after attempts with
      conventional techniques have failed. It should be mastered by all physicians
      involved in airway management. The technique is cost-effective because it avoids
      airway trauma and cancellation of surgical cases because of failed intubation.
      The flexible bronchoscope for airway management as a diagnostic, therapeutic, and
      problem-solving tool is not used to the degree that it deserves.
      Anesthesiologists and other critical care physicians should master the technique
      and use it on a daily basis. The widespread use of the instrument for airway
      management deserves encouragement.

PMID- 11444113
TI  - Flexible bronchoscopy in the elderly.
AB  - The established roles of flexible bronchoscopy in patients with diverse
      respiratory diseases, together with the demographic imperative posed by the aging
      of the population, make it important to understand factors relevant to this
      procedure in the elderly and to identify ways to optimize its performance.
      Relatively few investigations address specific influences of age on bronchoscopy
      but suggest that older patients age alone neither requires major modification of
      the approach nor introduces unacceptable hazards. The crucial relationships
      between bronchoscopy, the prevalence of specific respiratory diseases under
      consideration, and the impact of the procedure on patient management algorithms
      must be addressed in the future prospective investigations of the process of care
      in the elderly.

PMID- 11444114
TI  - The emerging role of flexible bronchoscopy in pediatrics.
AB  - Great advances had been made in rigid instrumentation, with the introduction of
      the glass rod telescope. With relatively few exceptions, however, bronchoscopy
      was still performed primarily for therapeutic indications, such as the removal of
      foreign bodies from the airway. It would remain for the introduction of the
      flexible bronchoscope to stimulate the widespread development of diagnostic
      bronchoscopy in pediatric practice.

PMID- 11444115
TI  - Adult airway foreign body removal. What's new?
AB  - Signs and symptoms of adult FB aspiration are most often nonspecific.
      Misdiagnosis and delay in diagnosis frequently occur. Radiographic evaluation is
      helpful, but flexible bronchoscopy is the gold standard in the identification and
      localization of an airway foreign body. With increasing experience and
      development of better accessories, removal using a flexible bronchoscope under
      local anesthesia can be performed safely and successfully. Review of large series
      of FB removal indicates a success rate of 86% in more than 400 procedures with
      flexible bronchoscopy.

PMID- 11444116
TI  - Role of bronchoalveolar lavage in interstitial lung disease.
AB  - Bronchoalveolar lavage remains an important research tool in understanding ILD.
      It is still an important part of the clinical management of patients with ILD. It
      is most useful in detecting unusual forms of ILD. It helps the clinician narrow
      down the possible causes of the interstitial pattern. It also can confirm a
      clinical impression of certain conditions. Although rarely diagnostic, it is
      often supportive. In conjunction with high-resolution CT scan, most patients with
      ILD can be diagnosed using relatively noninvasive methods.

PMID- 11444117
TI  - Flexible bronchoscopy in molecular biology.
AB  - Flexible fiberoptic bronchoscopy has allowed researchers to use the bench to
      bedside approach in the study and therapy of lung diseases. Through bronchoscopy,
      the lung is a relatively convenient source of samples for the direct evaluation
      of human gene expression and function. Sampling of respiratory epithelium is
      performed by brushing with a cytology brush, whereas the epithelial lining fluid
      and the inflammatory cells in the bronchoalveolar space are obtained by
      bronchoalveolar lavage. Furthermore, bronchoscopy has been a cornerstone
      essential to gene therapy trials for lung disease.

PMID- 11444118
TI  - Rigid bronchoscopy in the twenty-first century.
AB  - Rigid bronchoscopy, a procedure more than 100 years old, now has been performed
      in three centuries. The "open tube" bronchoscope provides safe access to the
      lower airways and has proved to be compatible with newer, more sophisticated
      therapies as they have been introduced into the practice of bronchology. The
      twenty-first century surely will provide the bronchoscopist with exciting new
      diagnostic and therapeutic tools for the management of lung diseases, and it is
      likely that the rigid bronchoscope will continue to play an important role in
      delivering these tools to the airways. Pulmonologists need to appreciate the use
      of this classic instrument and prevent rigid bronchoscopy from becoming a
      forgotten art.

PMID- 11444119
TI  - Training bronchoscopists for the new era.
AB  - Gustav Killian introduced bronchoscopy a little more than a century ago. At that
      time, the only way others could learn to perform bronchoscopy was by one-on-one
      tutoring, using a rigid bronchoscope with no side portals and no imaging devices
      such as a television camera and monitor. One-on-one teaching remains an integral
      part of learning how to perform bronchoscopy well, but many new technologies have
      emerged that make it far less labor intensive to train bronchoscopists. This
      article focuses on the training of bronchoscopists for the new era.

PMID- 11444120
TI  - Documentation in bronchology.
AB  - With the performance of more endoscopic procedures and newly developed diagnostic
      and therapeutic modalities, a wealth of information around the actual procedure
      is created. To date, accepted guidelines for standardized documentation are
      lacking. The authors present recommendations for minimal guidelines that may help
      to facilitate good documentation and also address future developments that will
      be possible with the help of computer-assisted approaches.

PMID- 11444121
TI  - Patient selection for dental implants. Part 2: Contraindications.
AB  - In today's dentistry, dental implants have become an excellent choice of
      treatment for multiple situations. The prognosis of this treatment modality, like
      any other in dentistry, is highly dependent on appropriate case selection. A
      multi-stepped data-gathering process, while lengthy, is very important. This
      process should include a patient interview to gather personal information, the
      chief complaint, medical history, and dental history. Extra-oral and intra-oral
      clinical examinations and a radiographic examination should be included.

PMID- 11444122
TI  - How to build patient loyalty.
AB  - When it comes to judging the quality of dental care they receive, patients often
      rely on more than the dental care itself. Patients judge quality by what they can
      see, touch, feel, and sense. A quality practice dedicated to nurturing loyal
      patients must create an environment that, in the eyes and perception of its
      patients, stands apart it from the competition. Many of today's service
      corporations can teach us how to market our practices and services and, in turn,
      keep our patients happy with their dental care and all aspects of the dental care
      experience.

PMID- 11444123
TI  - Treatment of the peg lateral incisor: a case study.
AB  - If guidelines are properly followed, porcelain laminate veneers can offer
      enviable and predictable results. Advantages of veneers include a highly esthetic
      outcome, durability and stability, all accomplished with a reasonably
      conservative approach. This case study illustrates the use of veneers to restore
      a peg lateral incisor of a young patient.

PMID- 11444124
TI  - Stress, disease, and dentistry.
AB  - There is increasing evidence that chronic stress, by suppressing the immune
      system, can lead to physical illnesses and, in turn, impact dental outcomes.
      Often, how patients cope with chronic stress is a common underlying factor in the
      outcome of both dental and systemic illnesses. Integrative dental medicine
      emphasizes an understanding of how dental diseases and systemic diseases
      interrelate. By developing positive coping strategies, raising self-awareness,
      and establishing a state of emotional balance, we can learn to identify the
      stressors in our lives and cope with them in more effective ways.

PMID- 11444125
TI  - Treating syncope in the dental office.

PMID- 11444126
TI  - Researchers discover genetic cause of bone disorder.

PMID- 11444127
TI  - Promising results for cancer-fighting mouthwash announced.

PMID- 11444128
TI  - American Pain Society: curb medication abuse but don't deprive patients.

PMID- 11444129
TI  - The hygienist's role in oral malodor treatment.

PMID- 11444130
TI  - Serving the hearing-impaired patient.

PMID- 11444131
TI  - Achieving an aesthetic smile design with integrated single- and multi-unit metal
      free restorations.

PMID- 11444132
TI  - Treatment planning for implants versus tooth retention: a contemporary dilemma.

PMID- 11444133
TI  - Utilizing pressed ceramic restorations to solve various aesthetic and functional
      dilemmas.

PMID- 11444134
TI  - Multiple uses for vinylpolysiloxane bite registration material.

PMID- 11444135
TI  - Remember the great teachers.

PMID- 11444136
TI  - Alternative orthodontic treatment for adult crossbites and overbites.

PMID- 11444137
TI  - Emergency medicine: preparation and basics of management.

PMID- 11444138
TI  - Pain control and the apprehensive patient.

PMID- 11444139
TI  - One-appointment indirect composite crowns: clinical technique.

PMID- 11444140
TI  - The use of glass ionomer materials in pediatric dentistry.

PMID- 11444141
TI  - Changing faces with indirect veneers.

PMID- 11444142
TI  - Common incidental periapical opacities encountered by the general dental
      practitioner.

PMID- 11444143
TI  - Video-assisted vision: a new approach to clinical dentistry.

PMID- 11444144
TI  - Using the computer for practice management and achieving job accountability.

PMID- 11444145
TI  - Chloride distribution in the CA1 region of newborn and adult hippocampus by light
      microscopic histochemistry.
AB  - GABA, the main inhibitory neurotransmitter in the central nervous system, exerts
      its effect by rendering the postsynaptic GABAA receptors permeable to chloride
      ions. Thus, depolarizing or excitatory effects of GABA, experienced in early
      postnatal life or in certain regions and/or conditions of the adult brain, is
      thought to be associated with a reversed transmembrane chloride gradient.
      However, there is only limited direct information about the correlation of the
      actual excitatory versus inhibitory effects of GABA and the local chloride
      distribution. Precipitation of chloride with silver is a potential way to
      immobilize and visualize chloride ions in biological tissue. We examined the
      applicability of light microscopic histochemistry, based on trapping tissue
      chloride with silver ions during freeze-substitution or aldehyde fixation, to
      visualize the chloride distribution in hippocampal slices. The freeze
      substitution procedure yielded better chloride retention while with aldehyde
      fixation tissue preservation was more appropriate. Both methods were qualitative
      only, had limited applicability to the superficial 20-30 microns of slices, but
      were able to demonstrate a reduced extracellular-to-intracellular chloride
      gradient in the CA1 pyramidal neurons of the newborn hippocampus as compared to
      adult animals. In the 4-aminopyridine model of epilepsy, redistribution of
      chloride from extracellular to intracellular space could also be demonstrated.

PMID- 11444146
TI  - Distribution of type-1 and type-2 angiotensin receptors in the normal human lung
      and in lungs from patients with chronic obstructive pulmonary disease.
AB  - This study was designed to examine the cellular distribution of the angiotensin
      II type-1 (AT1) and type-2 (AT2) receptors in the normal human and pathological
      human lung. Riboprobes were prepared against specific portions of each receptor
      DNA and labelled with FITC for detection using an anti-FITC antibody in
      combination with the alkaline phosphatase-anti-alkaline phosphatase technique and
      new Fuchsin. These were used to detect the presence of receptor mRNA in the lung.
      Specific antibodies were used to detect receptor protein in cells by
      immunocytochemistry. Image analysis was used in order to semi-quantify receptor
      density. AT1 receptor mRNA and protein were localised on vascular smooth muscle
      cells, macrophages and in the stroma underlying the airways epithelium probably
      relating to underlying fibroblasts. The AT1 receptor protein was not expressed in
      the epithelium although there was a low level of mRNA. In contrast, AT2 receptor
      RNA and protein was observed in the epithelium, with strong staining on the
      bronchial epithelial cell brush border and also on many of the underlying mucous
      glands. The AT2 receptor was also present on some endothelial cells. These
      findings were supported by the presence of mRNA in each case. In patients with
      chronic obstructive pulmonary disease, there was a five- to sixfold increase in
      the ratio of AT1 to AT2 receptors in the regions of marked fibrosis surrounding
      the bronchioles. This correlated well with the reduced lung function as expressed
      by the forced expiratory volume.

PMID- 11444147
TI  - Autometallography allows ultrastructural monitoring of zinc in the endocrine
      pancreas.
AB  - Zinc is intimately involved in insulin metabolism, its major known role being the
      binding of insulin in osmotically stable hexamers in beta-cell granules. To
      investigate the anatomical distribution of zinc ions necessary for insulin
      binding we examined the rat pancreas by autometallography (AMG). AMG demonstrates
      chelatable zinc and is a sensitive marker for zinc in vesicles and also a
      surrogate marker for recently described zinc pumps regulating intravesicular zinc
      metabolism. Zinc ions were found in alpha- and beta-cell granules, primarily in
      the periphery of the granules. Only occasionally was zinc seen in other islet
      cell types. AMG allows the study of the microscopic and ultrastructural
      localisation of free zinc ions in the pancreas. The applicability of the method
      at the ultrastructural level in particular makes AMG a very sensitive tool in
      future studies on the role of zinc ions in the pancreas.

PMID- 11444148
TI  - Guanylin in the human pancreas: a novel luminocrine regulatory pathway of
      electrolyte secretion via cGMP and CFTR in the ductal system.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a channel and
      regulator protein that is crucially involved in transepithelial ion transport. In
      the exocrine pancreas, the CFTR-mediated secretion of an electrolyte-rich fluid
      is a major but as yet incompletely understood function. We show here that the
      peptide guanylin is a specific activator of CFTR function in the human pancreas
      implicating regulation of pancreatic electrolyte secretion. Guanylin and its
      affiliated signaling and effector proteins including guanylate cyclase C, cGMP
      dependent protein kinase II, CFTR, and the epithelial Cl-/HCO3- exchanger, anion
      exchanger 2, are highly expressed in the human pancreas. Guanylin is localized
      specifically to the typical centroacinar cells and proximal duct cells which,
      based on its additional presence in the pancreatic juice, is obviously released
      luminally into the pancreatic ducts. The guanylin receptor and the respective
      functional downstream proteins are all confined to the apical membrane of the
      duct cells implicating an as yet unknown route of luminal regulatory pathway of
      electrolyte secretion in the ductal system. Functional studies in two different
      human pancreatic duct cell lines expressing the CFTR Cl- channel that is
      functionally intact in CAPAN-1 cells but defective (delta F508) in CFPAC-1 cells
      clearly identify guanylin as a specific regulator of pancreatic CFTR channel
      function. Whole-cell patch-clamp recordings in CAPAN-1 cells revealed that
      forskolin induces an increase of Cl- conductance mediated by cAMP. In contrast,
      guanylin increased Cl- conductance in the same cells via cGMP but not cAMP; the
      respective membrane current was largely blockable by the sulfonylurea
      glibenclamide. In CFPAC-1 cells, however, neither guanylin nor forskolin produced
      a current activation. Based on the present findings we conclude that guanylin is
      an intrinsic pancreatic regulator of Cl- current activation in pancreatic duct
      cells via cGMP and CFTR. Remarkably, in the pancreas guanylin may exert its
      function through an intriguing luminocrine mode via the pancreatic juice.

PMID- 11444149
TI  - Molecular cloning and developmental expression of rat fibroblast growth factor
      receptor 3.
AB  - Fibroblast growth factors (FGFs) are involved in the control of a variety of
      biological functions including regulation and differentiation of various cell
      types. Furthermore, they play important roles in the processes of regeneration,
      angiogenesis, and chemotaxis. The family of FGF receptors (FGFRs) comprises four
      members, FGFR-1 to -4, which exist in several differentially expressed splice
      variants. Except for FGFR-3, primary structures and expression of the three other
      FGFRs have been described in the rat system. Although expression studies with
      heterologous probes of FGFR-3 from mice have been performed in the rat system,
      these analyses were limited and the complete set of receptors has not yet been
      revealed. To understand the developmental functions of FGFR-3, it is important to
      elucidate the expression pattern in embryos of different stages. In this study,
      we have isolated a cDNA of FGFR-3 from rat brain. Expression analyses by RT-PCR
      of adult rat revealed expression in several tissues, however, expression levels
      were highest in lung and brain. During embryonic development, FGFR-3 displays a
      diffuse expression in most tissues at embryonic day 14 (E14), as observed by in
      situ hybridization experiments. In E18 the expression pattern is more restricted,
      showing strong signals in spinal cord, dorsal root ganglia, cortex, chondrocytes,
      and endothelial cells. The temporal and spatial pattern of FGFR-3 expression
      suggests specific functions in several tissues during development.

PMID- 11444150
TI  - Colocalization of beta 1,4galactosyltransferase with mannose 6-phosphate receptor
      in monensin-induced TGN-derived structures.
AB  - Previously, we demonstrated that beta 1,4galactosyltransferase (gal-T1)
      reversibly segregates from alpha 2,6sialyltransferase (ST6Gal) to swollen
      vesicles after monensin treatment of the cells. To further explore this
      phenomenon, we investigated the response to monensin of various Golgi proteins.
      Within 30 min of monensin treatment, gal-T1 moved from the Golgi apparatus, as
      defined by localization of giantin, to swollen vesicles whereas ST6Gal, alpha
      2,3(N)sialyltransferase, mannosidase II, and N-acetylgalactosaminyltransferase 2
      remained associated with the Golgi apparatus. Stably transfected CHO cells
      exhibited a similar phenomenon of monensin-induced displacement of recombinant
      gal-T1 to swollen vesicles while recombinant ST6Gal remained colocalized with
      endogenously expressed giantin. Gal-T1 and the cation-insensitive mannose 6
      phosphate receptor colocalized in swollen vesicles as observed at both light and
      electron microscopic levels. When monensin was replaced by chloroquine, gal-T1
      remained arrested in swollen vesicles. Brefeldin A treatment known to cause
      relocation of Golgi-associated gal-T1 to the endoplasmic reticulum had no effect
      on gal-T1 trapped in swollen vesicles. This evidence suggests that monensin
      blocks gal-T1 trafficking in post-Golgi structures and argues against swelling of
      gal-T1-containing trans Golgi cisternae as previously assumed.

PMID- 11444151
TI  - Immunohistochemistry of the golden hamster pituitary during chronic
      administration of diethylstilbestrol: a quantitative analysis using confocal
      laser scanning microscopy.
AB  - The aim of this study was to examine by immunohistochemistry the morphologic
      changes affecting pituitary cell populations in male Syrian hamsters undergoing
      chronic exposure (3 days to 9 months) to diethylstilbestrol (DES). Cell
      proliferation in the hypophysis was monitored by the immunohistochemical
      demonstration of S-phase cells after pulse labeling with 5-bromo-2'-deoxyuridine.
      Cell proliferation analysis was combined with the identification of different
      cell populations by immunostaining with antisera raised against hypophyseal
      hormones. Sections processed for double-label immunofluorescence were examined by
      confocal microscopy. In the adenohypophysis, the relative surface occupied by
      gonadotrophs and thyrotrophs decreased rapidly during the first months of
      treatment while corticotroph and somatotroph populations remained unaffected.
      Accordingly, the incidence of S-phase cells in these four cell populations was
      lower than or similar to control values. In contrast, lactotrophs increased
      gradually during the first month of exposure to DES to reach a maximum value at 2
      4 months. At the beginning, this increase was primarily due to hyperplasia but
      later on it also involved cellular hypertrophy. Somatomammotrophs did not seem to
      be involved in this model. In the pars intermedia, the labeling index of
      melanotrophs rose rapidly to reach values 5-6 times higher than controls. After 4
      months, neoplasms originating from the pars intermedia were seen invading both
      the neuro- and the adenohypophysis. At the end of treatment, the pituitary was
      markedly enlarged resulting from the development of an adenoma of the pars
      intermedia.

PMID- 11444152
TI  - Heat shock proteins, HSP25 and HSP70, and apoptosis in developing endocardial
      cushion of the mouse heart.
AB  - Formation of the atrioventricular channels and valves from the endocardial
      cushion occurs through growth and remodeling of the initial endocardial cushion.
      This process requires balanced coordination of proliferation and apoptosis by
      still unknown factors. To detect a possible role for the heat shock proteins 25
      and 70 (HSP25 and HSP70) as apoptosis-associated proteins and differentiation
      factors in the development of the endocardial cushion, we analyzed their temporal
      and regional occurrence during cell proliferation and apoptosis in E11-E17
      embryos. The distribution and timing of these events and factors were consistent
      with the hypothesis that HSP25 is related to myocardial development whereas HSP70
      is related to differentiation of the endocardial cushion by cell proliferation
      and apoptosis.

PMID- 11444153
TI  - Effects of childhood physical abuse on course and severity of substance abuse.
AB  - The present study sought to assess the course and severity of Substance Related
      Disorder (SRD) in relation to childhood physical abuse (CPA) using retrospective
      data on CPA and current indices of substance use, abuse, and related morbidity. A
      total of 642 patients were assessed, of whom 195 (30.4%) experienced CPA, were
      assessed in two university medical centers with Alcohol-Drug Programs located
      within departments of psychiatry. A research assistant obtained demographic data,
      family history of substance abuse, problems related to substance abuse, and
      treatment of substance abuse. Data on severity included two measures of SRD
      associated problems (one patient-rated and one psychiatrist-rated), substance
      abuse vs. dependence, self-help activities, and previous treatment. The study
      found that patients with CPA were more likely to be women, have lower
      socioeconomic status, and have more extended family members with substance abuse.
      Their substance abuse was more severe on five out of six severity measures.
      Patients with CPA showed more lifetime treatment on three out of four measures.
      Physical abuse during childhood resulted in a more morbid course of substance
      abuse later in adulthood. Although female gender and lower SES were both
      associated with CPA, the relationships were separate (i.e., women did not have
      lower SES).

PMID- 11444154
TI  - Gradual dose taper following chronic buprenorphine.
AB  - This paper describes the time course of withdrawal and relapse in opioid
      dependent volunteers (n = 8) who completed a gradual outpatient buprenorphine
      dose taper (28 days). Compliance with treatment was very high, as evidenced by
      clinic attendance (96-100%). Urinalysis showed that 6 of the 8 volunteers had
      relapsed to opiates by the end of the dose taper, even though reports of
      withdrawal were generally low. Relapse may have been triggered by a desire to re
      experience the drug's positive subjective effects, craving, or low motivation to
      remain drug-free. A longer taper combined with an expanded range of treatments
      may improve prognosis.

PMID- 11444155
TI  - The role of alcohol use in intimate partner femicide.
AB  - The purpose of this study was to examine alcohol use by victims and perpetrators
      as a risk factor for intimate partner violence and femicide. A case control
      design was used to describe alcohol use among Femicide/Attempted Femicide victims
      (n = 380), Abused Controls (n = 384) and Non-Abused Controls (n = 376), and their
      intimate partners. Telephone interviews of proxies (family members or friends) of
      femicide victims and actual survivors of attempted femicide were conducted in 10
      cities. The purpose of the interviews was to gather information about
      relationship violence and alcohol use by femicide victims, attempted femicide
      survivors, and their perpetrators. Telephone interviews of controls, recruited
      from the same cities by random digit dialing, were also conducted. Perpetrator
      problem drinking was associated with an eight fold increase in partner abuse (e
      beta = 8.24, p < .0001) and a two fold increased risk of femicide/attempted
      femicide (e beta = 2.39, p = .001), controlling for demographic differences.

PMID- 11444156
TI  - The links between alcohol, crime and the criminal justice system: explanations,
      evidence and interventions.
AB  - Many studies indicate that alcohol abuse and dependence are closely linked with
      the criminal justice system (CJS). Alcohol was consumed prior to about half of
      all homicides and assaults, and nearly 40 percent of state prisoners report
      committing their current offense under the influence of alcohol. Alcohol abuse
      cost approximately $13 billion in 1992 non-health related costs. This article
      seeks to address this burden on the CJS and society. It presents a conceptual
      framework for explaining the alcohol-crime nexus, reviews empirical evidence of
      the complex associations between alcohol consumption and crime, and links these
      with promising intervention strategies to reduce alcohol-related crime.

PMID- 11444157
TI  - Interest in smoking cessation among injection drug users.
AB  - We describe the degree of nicotine addiction and readiness to quit smoking among
      people with a history of injection drug use, comparing those in a methadone
      maintenance treatment program (MMTP) with active illicit drug injectors in a
      needle exchange program (NEP). Interview data were collected from 452 persons in
      Providence, RI, from July 1997 to March 1998. Ninety-one percent (91%) of the
      population currently smoked cigarettes. Smokers were more likely to be female and
      from an NEP. Higher nicotine dependence by the Fagerstrom Test for Nicotine
      Dependence was found in Caucasians, those with a Methadone dose greater than 80
      mg per day, those with less than high school education, and those with active
      alcohol abuse. Those more likely to be contemplating smoking cessation in the
      next six months were those from MMTP, older than 35, and without alcohol abuse.
      Although smoking cessation counseling should be offered to all smokers,
      interventions directed towards older individuals enrolled in MMTP may target the
      group most interested in smoking cessation.

PMID- 11444158
TI  - Reason for medical hospitalization among adult alcohol and drug abusers.
AB  - This study attempts to identify the associations between types of substance use
      and particular medical problems as causes of acute hospital admission on an
      inpatient substance abuse consultation service. Records of all consultations
      performed from 1994 to 1998 were analyzed. A total of 4,526 complete records were
      available. Cocaine (p < .01), heroin (p < .001), and injection drug (p < .001)
      users were more likely to be admitted to the hospital for infection. Both alcohol
      (p < .001) and marijuana (p < .001) users were more likely to be hospitalized for
      trauma related injuries. Individuals that used alcohol were also more likely to
      be admitted for the treatment of gastrointestinal disorders (p < .001).
      Clinicians who treat patients with these diagnoses should have a high index of
      suspicion of co-morbid substance use disorders. Effective treatment of substance
      use disorders can lead to a decrease in medical morbidity, improved outcomes for
      individual patients, and decreased costs for the health care system.

PMID- 11444159
TI  - An overview of controlled studies of adolescent substance abuse treatment.
AB  - Although several treatments for adolescents with substance use disorders are
      available, there are few well-controlled studies in the extant literature that
      compare these treatments for efficacy. This paper provides an overview of
      controlled treatment studies for adolescents with substance use disorders. It
      focuses specifically on five main treatment modalities: family-based and multi
      systemic interventions, behavioral therapy, cognitive behavioral therapy,
      pharmacotherapy, and twelve step approaches. Examples of adolescent-specific
      standardized assessment instruments are also provided, the inclusion of which may
      improve future treatment comparison studies. While the results look especially
      promising for cognitive behavioral therapy and family-based/multi-systemic
      therapies for adolescents with SUDs, most of the relevant studies fail to utilize
      validated outcome measures, making it difficult to conclude that one treatment
      approach is more effective than another.

PMID- 11444160
TI  - Safety and efficacy of risperidone in substance abusers with psychosis.

PMID- 11444161
TI  - Methylphenidate in stimulants abuse: three case reports.

PMID- 11444162
TI  - Serum thyroid-stimulating hormone measurement for assessment of thyroid function
      and disease.
AB  - Third generation thyroid stimulating hormone (TSH) assays have emerged as the
      single most useful test of thyroid function, and are used widely and
      appropriately as a screening test. TSH measurement alone may be misleading in
      complicated patients and those undergoing treatment for thyroid dysfunction.
      Before obtaining thyroid function tests, clinicians need to consider whether the
      patient might have pituitary or hypothalamic disease or severe nonthyroidal
      illness, and whether assessment of the pituitary-thyroid axis reflects steady
      state conditions. Subclinical hyperthyroidism is associated with adverse effects
      on the skeleton and the heart, and is best assessed by measurement of serum TsH
      with a third-generation assay.

PMID- 11444163
TI  - Free thyroid hormone measurement. A critical appraisal.
AB  - The main purpose of free T4 and free T3 assays is to distinguish reliably between
      thyrotoxicosis, hypothyroidism, and the euthyroid state, an objective that cannot
      be attained with assays of total T4 and T3 because of hereditary and acquired
      variations in the concentrations of binding proteins. Effective correction for
      changes in the serum concentration of TBG can be achieved with numerous types of
      free hormone estimate, but other changes in binding are not well accommodated.
      Despite remarkable methodologic ingenuity, no current method reflects the free T4
      concentration in undiluted serum under in vivo conditions. Equilibrium dialysis,
      widely considered the reference method for free T4 measurement, is also subject
      to error, either preanalytic, owing to generation of NEFA in the sample leading
      to an overestimate of free T4, or analytic with underestimation of the effect of
      competitors to increase free T4. Current approaches to free T4 measurement are
      vulnerable to several method-dependent artifacts: abnormal albumin binding of T4
      or of the assay tracer, the inhibition of T4 binding to TBG by medications, and
      the effects of critical illness, especially in heparin-treated patients,
      pregnancy, and the abnormalities in sick premature infants. Because of systematic
      variation between methods (i.e., whether a technique is albumin dependent or
      prone to incubation or dilution artifacts), it is essential to consider
      methodologic details in evaluating free T4 estimates in these situations and
      whenever estimates of free T4 are clinically discordant. False-positive
      abnormalities are more frequent than false-negative results. When free T4 results
      are correlated with the serum TSH concentration with attention to the assumptions
      that define this relationship, the majority of false-positive results can be
      readily identified. If a free T4 anomaly remains unexplained on repeat sampling,
      it is appropriate to use an alternative free T4 method that depends on a
      different assay principle and to correlate the result with an authentic total T4
      measurement.

PMID- 11444164
TI  - Radioiodine uptake and thyroid scintiscanning.
AB  - This article reviews the technical aspects and clinical applications of the
      radioactive iodine uptake test and thyroid scintiscanning. The choice of
      radionuclide for the tests is discussed. The main uses of the radioactive iodine
      uptake test are to identify the cause of hyperthyroidism and to aid in the
      selection of the I-131 dose in the treatment of hyperthyroidism. Factors other
      than thyroid diseases that alter uptake results are identified. Thyroid
      scintiscanning is used in the identification of normal and ectopic thyroid
      tissue, in the diagnosis of the cause of a patient's hyperthyroidism, and as part
      of the evaluation of selected patients with thyroid nodules.

PMID- 11444165
TI  - Thyroid autoantibodies.
AB  - Although assays to detect thyroid autoantibodies have been available for more
      than 40 years, their place in the clinical management of thyroid disease has
      remained controversial; however, novel automated detection techniques using
      recombinant antigens are increasing the sensitivity and specificity of the
      assays, particularly for antibodies to the TSH receptor. In addition, new
      antigenic targets have been defined including the sodium-iodide symporter and
      four eye muscle proteins targeted in Graves' ophthalmopathy. This article
      summarizes the immunobiology, assay methodology and prevalence in thyroid
      diseases of each of the major thyroid autoantibodies before discussing the
      clinical indications for their use in thyroid diseases.

PMID- 11444166
TI  - Thyroid ultrasound.
AB  - Evaluation of the thyroid gland can be performed by several imaging techniques.
      Although ultrasound (US) lacks specificity for tissue diagnosis and can rarely
      distinguish benign from malignant disease, it can distinguish solid nodules from
      simple and complex cysts. It allows accurate estimation of thyroid size, gives a
      rough estimate of tissue density (echogenicity), shows vascular flow and velocity
      (color-flow Doppler), can identify regional lymphadenopathy, and aids in the
      accurate placing of needles for diagnostic or therapeutic purposes. In addition,
      it is widely available, relatively rapid and cheap, visualizes the whole anterior
      neck, and does not involve ionizing irradiation. This article aims at clarifying
      the role of US in clinical thyroidology by pointing to areas where the technology
      can aid in clinical decision making. It is argued that more clinician
      endocrinologists should master and use this technology for diagnostic and
      therapeutic purposes.

PMID- 11444167
TI  - Fine-needle aspiration biopsy of the thyroid.
AB  - The routine use of thyroid FNAB caused profound changes in the management of
      thyroid nodules. FNAB allows a prompt identification and treatment of thyroid
      malignancies and avoids unnecessary surgery in patients with benign lesions,
      improving quality of life in patients with thyroid nodules. Furthermore, FNAB
      provides guidance for the type of surgery and reduces costs of care. On average,
      standard FNAB is nondiagnostic in 25% to 40% of cases, which include inadequate
      specimens and indeterminate (suspicious) diagnoses. In addition, a small
      percentage of false-negative diagnoses occur, which are unavoidable and raise
      concern of a late diagnosis of cancer. To minimize the limitations of FNAB, every
      center should reach and maintain a high standard of expertise in all of the steps
      of smear preparation and interpretation. Alternative modes of sampling or sample
      preparation may result in a reduction of nondiagnostic samples and better
      accuracy. Every center should set up clinical guidelines tailored to their own
      FNAB results and including the evaluation of clinical data. More work is needed
      to increase the accuracy of FNAB in suspicious cases. Toward this goal a variety
      of molecular markers have been evaluated; although none of them are ideal, some
      are promising. More studies need to be carried out in larger series to further
      evaluate the accuracy of these markers in identifying specific cancer histotypes
      within the group of suspicious lesions. It is hoped that, in the near future, the
      routine use of a combination of these markers will cost-effectively improve the
      diagnosis of malignant nodules classified as suspicious on traditional cytology.
      Statistical methods such as bayesian analysis or neural networks can be
      advantageously used to integrate different relevant information derived from
      family and personal history, clinical data, cytologic results, and evaluation of
      molecular markers.

PMID- 11444168
TI  - Evaluation of substernal goiters using computed tomography and MR imaging.
AB  - Computed tomography and MR imaging are valuable techniques for determining the
      presence and extent of substernal goiters, their impingement on adjacent
      structures in the neck and chest, and whether mediastinal masses are thyroidal in
      origin. This article discusses the advantages and disadvantages of each technique
      and the radiologic characteristics of substernal goiters. Radiographic examples
      of both techniques are included to illustrate common clinical settings. Finally,
      suggestions for choosing which patients will benefit from scanning and which
      technique will safely provide the maximum information in various clinical
      settings are discussed.

PMID- 11444169
TI  - Clinical, metabolic, and organ-specific indices of thyroid function.
AB  - Presently there are a sufficient number of sensitive and specific tests of
      thyroid function to establish a diagnosis of thyroid disease with a high degree
      of precision. A variety of clinical situations, however, including but not
      limited to thyroid hormone resistance states, alterations in thyroid-binding
      proteins and nonthyroidal illness, challenge the clinician to evaluate the
      thyroid status of the patient beyond that which can be done with routine
      laboratory tests. This article reviews several clinical, cardiac, skeletal
      muscle, and other laboratory studies that have been suggested to complement the
      overall assessment of thyroid status.

PMID- 11444170
TI  - Serum thyroglobulin measurement. Utility in clinical practice.
AB  - Serum thyroglobulin measurement has greatly facilitated the clinical management
      of patients with differentiated thyroid cancer and a variety of other thyroid
      disorders. Thyroglobulin autoantibodies remain a significant obstacle to the
      clinical use of thyroglobulin measurement. The interpretation of any given
      thyroglobulin value requires the careful synthesis of all pertinent clinical and
      laboratory data available to the clinician. The diagnostic use of rhTSH
      stimulated thyroglobulin levels has greatly facilitated the follow-up of low-risk
      patients with thyroid cancer. Although the measurement of thyroglobulin mRNA from
      peripheral blood is likely to affect the future management of these patients, it
      is expected that serum thyroglobulin measurement will continue to have a
      principal role in the care of patients with differentiated thyroid cancer.

PMID- 11444171
TI  - Isotope imaging for metastatic thyroid cancer.
AB  - Many isotopes are available for imaging patients with suspected thyroid cancer
      recurrence and metastases. TSH-stimulated low-dose 131I whole-body scanning with
      serum thyroglobulin either by standard LT4 withdrawal or rhTSH stimulation is the
      preferred test for monitoring patients without palpable disease or elevated serum
      thyroglobulin on LT4 therapy (Fig. 5). This approach has the advantage of finding
      disease that may be amenable to 131I therapy, although low-dose 131I scans are
      less sensitive than are scans with other imaging agents. 123I has better imaging
      characteristics than 131I and has been shown to be equivalent or superior to low
      dose 131I in recent studies. As the availability of 123I increases and the cost
      decreases, this agent may replace 131I in imaging for recurrent or metastatic
      thyroid cancer. Patients who have an elevated serum thyroglobulin on LT4 therapy
      or after TSH stimulation but have a negative low-dose 131I scan require other
      imaging procedures to find the suspected disease. The authors currently perform a
      sensitive neck ultrasound to look for surgically remediable disease and consider
      a noncontrast CT scan of the chest to look for small pulmonary metastases that
      poorly concentrate low doses of 131I (Fig. 5). Fluoro-18-deoxyglucose PET, 99mTc
      MIBI, 201Tl, and 99mTc tetrofosmin are primarily useful in the setting of a
      negative whole-body 131I scan and elevated serum thyroglobulin. 18FDG-PET seems
      to have the highest sensitivity in this setting and would be the preferred
      imaging agent, but availability and cost are major issues (Fig. 5). Although some
      researchers have advocated these radiopharmaceuticals as first-line agents
      replacing 131I, there is little support for this position. This approach to
      imaging is not cost-effective because positive scans in these patients would most
      likely require 131I scintigraphy to determine whether the lesions are amenable to
      radioiodine therapy. 99mTc pertechnetate, 99mTc furifosmin, and somatostatin
      receptor scintigraphy have a limited role in imaging for recurrent or metastatic
      differentiated thyroid carcinoma. In choosing among 99mTc MIBI, 201Tl, and 99mTc
      tetrofosmin, the technetium label of sestamibi and tetrofosmin results in better
      image quality and faster imaging than 201Tl. Although 99mTc sestamibi and 99mTc
      tetrofosmin have not been compared in a large series, the higher tumor-to
      background ratio and consistently high sensitivities of 99mTc tetrofosmin suggest
      that it could potentially have additional value over 99mTc sestamibi, but there
      is still limited experience with 99mTc tetrofosmin.

PMID- 11444172
TI  - Genetic markers in thyroid neoplasia.
AB  - Cancer is a disease of genes. Detection of genetic abnormalities associated with
      cancers of various cell types can now be used for genetic counseling, diagnosis
      or treatment selection. In the case of thyroid cancer, genetic testing for
      mutations of the RET oncogene has had a profound effect on the management of
      medullary thyroid carcinomas. There is also considerable information on the
      genetic changes associated with development and progression of cancers of thyroid
      follicular cells, although these have not yet proven to be of practical value for
      clinical diagnosis or to guide prognosis and therapy.

PMID- 11444173
TI  - [Fetal breathing movements and onset of delivery at term].
AB  - It has been studied the relation between fetal breathing activity and labor among
      216 patients in uncomplicated pregnancies at term. It has been also described the
      value of fetal breathing movements in the evaluation of fetal well-being. Among
      patients where fetal breathing movements were absent 81.9% women delivered within
      3 days since ultrasonographic examination. And among patients with visible fetal
      breathing activity only 25.0% delivered within this period. The analysis of
      newborn condition based on Apgar score in pregnant women with or without fetal
      breathing movements showed no significant statistical differences. The absence of
      fetal breathing movements has no prognostic value concerning the evaluation of
      fetal well-being in antepartum period. The cessation of fetal breathing activity
      facilitates to prognose the time of labor in mature pregnancies.

PMID- 11444174
TI  - [Analysis of selected parameters of maternal and fetal status during stimulation
      of fetal lung maturation].
AB  - At patients threatened with premature childbirth the influence of glicocorticoids
      on short and tong-term fetal heart rate variability and the occurrence of
      respiratory arrhythmia was evaluated. It has been ascertained statistical
      significant lowering of the incidence of fetal respiratory arrhythmia and short
      term variability. Described changes had a temporary character and surrendered of
      normalization in the course 72 of hours after last use of glicocorticoids. The
      influence of glicocorticoids on select biochemical and biophysical parameters of
      state pregnant women was also studied. One specified occurrence of incidental
      symptoms in road drove of therapy. Pregnant women in road of treatment
      glicocorticoids have also observed a temporary weakness of feeling of fetal
      movements.

PMID- 11444175
TI  - [Evaluation of the value of hysteroscopy or doppler ultrasonography for
      monitoring treatment effects of radiotherapy in patients with cervix carcinoma].
AB  - The aim of this study was to investigate the useful of colour flow doppler (CDF)
      and hysteroscopy to determine the endometrium status in endometrial cancer
      patients who were treated by radiotherapy alone. The study group comprised 33
      patients. There were hysteroscopy and CDF performed in obligatory regular
      periods. High useful of hysteroscopy was confirmed. It appeared 89% of
      sensitivity and 91% of specificity. CDF sensitivity was 69% and specificity 75%.
      Absence of the flow signal in endometrial tissue was correlated with no of
      malignant pathology in uterus. Pulsatility and resistance indexes in CDF were not
      characterised for histopathology status of endometrium.

PMID- 11444176
TI  - [Integrin alpha-6 in cervix neck squamous cell carcinoma HPV 16/18 positive and
      negative].
AB  - In the present paper we study expression of alpha-6 integrin in normal
      paraepidermal epithelium, in CIN and in cervical invasive carcinoma HPV 16/18
      positive and negative. The results suggest that alpha-6 integrin might be a
      marker for the evaluation of malignancy of squamous cell carcinoma. There is no
      correlation between the expression of alpha-6 integrin and the presence of HPV.

PMID- 11444177
TI  - [Evaluation of risk factors after intraperitoneal chemotherapy in patients with
      ovarian cancer].
AB  - DESIGN: The authors sought to evaluate risk factors of patients with ovarian
      cancer treated with intraperitoneal cisplatin based chemotherapy (IPC). MATERIAL
      AND METHODS: From January 1996 to December 1998, 24 patients with recurrent or
      persistent ovarian cancer were treated. We divide them in two groups first
      beneath 65 year old (19 patients), second above 65 year (5 patients), and in
      three groups with residual microscopic diseases, residual below 0.5 cm, and
      between 0.5 and 2 cm in the time of the beginning of treatment with IPC. We also
      estimate stage (FIGO) as a risk factor. RESULTS: In the first group the study
      showed (CRP) among 9 patients (SD) among 2 patients PD in among patients. In the
      second group CRP were observed among 2 patients PD among 2 patients, and SD 1
      patient. CONCLUSION: IPC is the valuable method of second line chemotherapy for
      ovarian cancer. Age is not a risk factor in IPC. IPC prolongs survival in ovarian
      cancer patients, progression free survival, and gives only slightly adverse
      effects.

PMID- 11444178
TI  - [Analysis of hormone profile in women during the pre- and postmenopausal period
      using hormone replacement therapy, and analysis of the mammography image in these
      women].
AB  - The hormonal profile and mammography results were analysed in 120 women in
      premenopause (group A) and 130 in postmenopausal period (group B). The analysis
      developed biphasic menstrual cycle, with high progesterone levels in the second
      cycle's period in 57 subjects (group A--mean P concentration--53.7 nmol/ml), and
      elevated E2 levels in monophasic cycle in 63 subjects (group A2--man E2 205.4
      pg/dl). In case of post-menopausal women mean E2 level during therapy was 104.6
      pg/dl. In examined group 8 subject have been undergoing hormonal replacement
      therapy for 1-3 years, 30 of them for 5 years, 20 more than 5 years. In
      mammography in one case from group A1 with high progesterone concentration
      abnormally opaqueness has been observed. Histological examination confirmed
      incidence of cancer cells. No other changes have been observed. High serum
      progesterone concentration in pre-menopausal women increase risk of cancer.

PMID- 11444179
TI  - [Evaluation of incidence of Chlamydia trachomatis infections among the group of
      infertile women diagnosed by laparoscopy, and based on properties of Chlamydia
      trachomatis in the cervical canal, peritoneal fluid and ovarian cyst puncture].
AB  - The number of 75 patients who underwent diagnostic et operative laparoscopy was
      analysed. The percentage of infection cases caused by Chlamydia Trachomatis was
      9.33% investigations proved correlation between fallopian tube factor and
      infection. It seems that pelvic infection not always undergoes with infection of
      uterine cervix.

PMID- 11444180
TI  - [Comparison of the frequency of selected gynecologic operations conducted as
      laparotomy and laparoscopy during 1993-1997].
AB  - The aim of the study was to compare frequency of four gynecological operations:
      myomectomy, tubal surgery, cystectomy and operative management of ectopic
      pregnancy, performed by laparotomy or laparoscopy, by the same team of surgeons.
      In the years 1994-1997 in Division of Reproduction Poznan University Medical
      School 647 cystectomies, 208 myomectomies, 68 tuboplasties and 50 surgical
      treatments of ectopic pregnancy were done. Among 973 operations--684 (70.3%) were
      performed by laparoscopy. There was a gradual tendency in increasing endoscopic
      procedures. Comparing the year 1994 and 1997 percentage of operations performed
      by laparoscopy significantly changed: In tuboplasty from 83% to 95%, cystectomy
      from 35.9% to 80.3%, ectopic pregnancy from 61.5% to 91.7% and myomectomy from
      52.7% to 61.5%. Patient hospital stay decreased significantly after laparoscopic
      procedures (from 5.1 days to 3.25 days). During the study period open surgery
      followed laparoscopy only in 8 cases (1.1%) because of complications or technical
      difficulties. CONCLUSION: 1. Operative laparoscopy is a safe and effective
      procedure, in many cases replacing open surgery. 2. Shortening of hospital stay
      and recovery period after laparoscopy is one of the main advantages of this
      method of treatment.

PMID- 11444181
TI  - [The value of skin densitometry in diagnosis of decreased bone mass in the spine
      of women during the period around and post-menopause].
AB  - OBJECTIVE: In peri- and postmenopausal women, the association of skin thickness
      with bone mass is well described, and a low skin thickness is a useful predictor
      of osteoporosis. In this study the association between skin thickness and bone
      mass of lumbar spine in peri- and postmenopausal women was assessed; and the
      potential for skin thickness as a screening test for osteoporosis evaluated.
      DESIGN/METHODS: Skin thickness was measured at the arm by ultrasonography (probe
      22 MHz). Bone mass was measured at lumbar spine by dual-energy X-ray
      absorptiometry. One hundred and three peri- and postmenopausal women were
      studied. RESULT: Successive decrease of skin thickness going along with the loss
      of lumbar spine bone mass was found. There was a statistically significant
      difference (p < 0.05) in skin thickness between group of females with normal bone
      mass and group with osteoporosis. CONCLUSIONS: Ultrasound skin measurement is a
      very simple method which can be used in the diagnostics of osteoporosis of the
      lumbar spine in peri- and postmenopausal women.

PMID- 11444182
TI  - [Complications caused by nonabsorbable surgical sutures].
AB  - The author presents the case of complication caused by nonabsorbable silk
      surgical sutures which occurred two years and seven month after cesarean section
      and next hysterectomy performed at the same time. The sutures caused the
      formation of big vesical stone as well the appearance of acute recurrent
      pyelonephritis and stricture of the urethra. After lithotripsy, the patient
      completely recovered.

PMID- 11444183
TI  - [Eradication, elimination of congenital rubella syndrome].
AB  - The strategies of World health Organisation for elimination of congenital rubella
      syndrome were presented. The ways of prevention of congenital rubella syndrome by
      appropriate immunization programs were discussed. The concomitant adverse effects
      and risks were presented. On the basis of epidemiology of rubella in Poland the
      authors propose the adjusted vaccination policy.

PMID- 11444184
TI  - [The role of nitric oxide in carcinogenesis and progression of neoplastic
      processes].
AB  - The aim of the review is to outline the current knowledge about the role of
      nitric oxide in the processes of proliferation and apoptosis in tumor. Special
      emphasis has been placed on its direct cytotoxic influence on a cell where as a
      highly active free radical it may compromise different cellular functions. Nitric
      oxide literature, regarding its role in the pathogenesis of some gynecological
      and breast cancer has been briefly reviewed.

PMID- 11444185
TI  - Multimegapixel images in histopathology.
AB  - OBJECTIVE: To describe methods and procedures for the assembly of very large
      scale microscopic image arrays. STUDY DESIGN: Microscopic imagery was recorded on
      different video microphotometers, equipped either with a three-chip CCD Sony MD
      760 (Park-ridge, New Jersey, U.S.A.), a COHU vidicon (San Diego, California,
      U.S.A.) or a PROGRES camera (JenOptik, Jena, Germany), yielding image tiles of
      512 x 470, 512 x 470 or 1,496 x 1,120 pixels, respectively. The slide was moved
      while mounted on a Maerzheuser scanning stage with 0.1-micron precision, under
      computer control. The MERGE software. (Optical Sciences Center, University of
      Arizona, Tucson, Arizona, U.S.A.) was written in C and currently implemented on a
      Sun. Ultra Sparc 2 computer (Sun Microsystems, Palo Alto, California, U.S.A.).
      RESULTS: The MERGE program allows the assembly of very large scale digitized
      image arrays preserving exact tile alignment such that even within a single
      nucleus, highly precise registration is maintained. Images up to 150 megapixels
      have been assembled, although most practical applications required assembly of
      only 60-300 tiles. CONCLUSION: The single limiting effect of assembling very
      large image arrays is the problem of angular misalignment between CCD scan line
      orientation and scanning stage travel direction. For misalignment of even less
      than 1 degree, very large arrays need substantial tile overlap. For object areas
      extending over only 5-10 mm, the effects can be controlled.

PMID- 11444186
TI  - Quantitative assessment of oxyphilic cell lesions of the thyroid gland on fine
      needle aspiration samples.
AB  - OBJECTIVE: To assess the possible contribution by a multiparametric quantitative
      approach to the cytologic diagnosis of oxyphilic cell (OC) thyroid lesions. STUDY
      DESIGN: Ten cases of chronic lymphocytic (Hashimoto) thyroiditis and 10 nodular
      goiters containing oxyphilic cells plus 20 cases of tumors subsequently
      classified as oxyphilic cell adenomas (10 cases) or oxyphilic cell well
      differentiated carcinomas (10 cases) were evaluated. The study was performed on
      May-Grunwald-Giemsa-stained smears for planimetric measurements. The same smears
      were destained and Feulgen restained for densitometric measurements. The latter
      were performed using static cytometry equipment measuring 100 and 20-30
      lymphocytes per case for the determination of integrated optical density (IOD).
      The following parameters were considered: nuclear area, perimeter, maximum
      diameter, form ELL, form PE, IOD, 5c exceeding rate (5cER) and visual
      classification of histograms as euploid, polyploid and aneuploid. RESULTS: Mean
      nuclear area of carcinomas was smaller than that of adenomas, goiter and
      thyroiditis. Nuclear area was larger in adenomas than in other benign lesions and
      carcinomas. All the other planimetric parameters were similar in the lesions
      examined. Four carcinomas and three adenomas were aneuploid, and all the rest
      were euploid. All the cases of thyroiditis and goiter were euploid or polyploid;
      four thyroiditis cases showed polyploid histograms and 5cER values > 1.
      CONCLUSION: Morphometric and densitometric procedures have a limited role in the
      discrimination of OC lesions, but small nuclear area values may be useful in
      distinguishing OC carcinoma from other lesions. The role of densitometry seems
      even more limited because aneuploid histograms may be found among adenomas and
      carcinomas. Further studies are needed to explain polyploidy and 5cER > 1 in
      Hashimoto thyroiditis.

PMID- 11444187
TI  - Nucleolar morphometry in fine needle aspiration biopsies of the prostate.
AB  - OBJECTIVE: To find efficient morphometric nucleolar features for distinguishing
      different prostatic atypia groups in fine needle aspiration biopsies. STUDY
      DESIGN: A computerized interactive morphometry program was used to outline
      nucleoli of prostate cells. The samples were divided into three groups: group 1
      (definitely benign [n = 10] and atypical but benign [n = 13]), group 2
      (moderately atypical [n = 11] or highly suspicious [n = 13]) and group 3
      (definitely malignant [n = 17]). RESULTS: The analysis revealed a difference in
      the number of nucleoli between definitely benign samples and other atypia groups
      but not between the latter. Nucleolar size features were best in distinguishing
      between atypia groups. The sample-associated mean size features were more
      powerful than cell group-associated size features. CONCLUSION: The sample
      associated mean area, defined from cells selected by an experienced cytologist,
      if larger than 2 micron 2, was strongly associated with definitely malignant
      samples. The same was true for the largest nucleolar area if larger than 5.0
      micron 2. Morphometric nucleolar size features appeared efficient in
      distinguishing between definitely malignant and other samples.

PMID- 11444188
TI  - Nuclear texture features for classifying benign vs. dysplastic or malignant
      squamous epithelium of the larynx.
AB  - OBJECTIVE: To search for nuclear features and feature combinations able to assess
      malignancy and premalignant changes on tissue sections of laryngeal squamous
      epithelium. STUDY DESIGN: A total of 139 lesions of benign changes (BC) (n = 44),
      epithelial dysplasias (ED) (n = 50) and invasive laryngeal cancer (LC) (n = 45)
      were retrieved from archival pathology specimens. The goal of this study was to
      identify the best features or feature combinations that discriminate BC from LC
      and also reflect the degree of ED. In order to verify the results on independent
      data, the groups were split into two separate subgroups, one for training and one
      for testing. RESULTS: On the test set of slides, the overall correct
      classification of BC vs. LC cases was 82% using only one feature, fractal2_area.
      This classification rate could be increased to 91% when a discriminant function
      based on 10 features was used. However, this gain was not significant.
      CONCLUSION: Fractal texture features can be used to assess malignancy on tissue
      sections as an alternative to DNA measurement. In this study feature combinations
      did not significantly improve classification rates.

PMID- 11444189
TI  - Morphometric characterization of endometrial glands using quantitative cytology.
AB  - OBJECTIVE: To determine the usefulness of the combination of confocal laser
      scanning microscopy (CLSM), image cytometry and three-dimensional (3D) imaging
      for analyzing architectural changes indicative of endometrial hyperplasia and
      grade 1 adenocarcinoma. STUDY DESIGN: Papanicolaou-stained endometrial samples (n
      = 180) were analyzed for specific cellular characteristics and analyzed by CLSM.
      Confocal images were obtained and then analyzed cytometrically and used for 3D
      reconstruction. RESULTS: Values obtained after image cytometry and 3D imaging
      increased significantly (P < .01) with the degree of cellular atypia. CONCLUSION:
      The combination of CLSM, image cytometry and 3D imaging is a valuable method for
      differential diagnosis of endometrial hyperplasia and grade 1 adenocarcinoma.

PMID- 11444190
TI  - Roles of DNA cytometry and detection of EBERs in predicting a diagnosis of
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: To analyze the suitability of DNA cytometry and detection of Epstein
      Barr virus (EBV)-encoded RNAs (EBERs) on nasopharyngeal brushings for predicting
      a diagnosis of nasopharyngeal carcinoma (NPC). STUDY DESIGN: Cytologic
      preparations in 66 cases suspicious for NPC were evaluated for NPC diagnosis in
      comparison with the histologic diagnosis. Based on cytologic examination, 38
      cases containing cytologically proven cancer and 8 cases interpreted as
      cytologically negative for cancer with adequate cellularity in the smear
      specimens were analyzed for DNA ploidy with an image analyzer and for EBER
      expression by in situ hybridization (ISH). RESULTS: Based on the cytologic
      diagnosis, DNA aneuploidy analysis, DNA nondiploidy analysis and EBER detection
      demonstrated a sensitivity of 50%, 84% and 92%, respectively, with the same
      specificity, 100%, for predicting a diagnosis of cancer. Their negative
      predictive values were 30%, 57% and 73%, respectively. There was a significant
      difference between DNA aneuploidy analysis and EBER analysis in sensitivity (P <
      .001) and in negative predictive value (P < .05) but not between DNA nondiploidy
      analysis and EBER analysis even though EBER analysis showed a slightly higher
      value in both parameters (P > .1 and P > .5, respectively). CONCLUSION: ISH for
      EBERs in cytologic smears showed a role superior to that of DNA aneuploidy
      analysis in the diagnosis of NPC. Considering its advantages of simple
      experimental conditions and lower cost as compared with DNA measurement, EBER
      detection can play a practical and important diagnostic role in patients
      suspected of having primary NPC.

PMID- 11444191
TI  - Nasopharyngeal carcinoma heterogeneity of DNA content identified on cytologic
      preparations.
AB  - OBJECTIVE: To evaluate tumor heterogeneity of DNA content in nasopharyngeal
      carcinoma (NPC) performed on cytologic specimens. STUDY DESIGN: Image cytometric
      analysis of DNA ploidy status of 40 NPCs was performed on nasopharyngeal brushing
      smears stained with the Feulgen method after hematoxylin eosin staining. If the
      DNA distribution pattern from the same tumor exhibited diploid, aneuploid or/and
      tetraploid peaks or some combination of these patterns, the presence of tumor
      heterogeneity of DNA content was identified. RESULTS: Thirty-four cases (85%) had
      a nondiploid DNA pattern among the 40 NPCs. Twenty-eight cases exhibited tumor
      heterogeneity of DNA content (70%). Of the 28 tumors, 13 (46%) had a combination
      of diploid and tetraploid patterns, 10 (37%) had a combination of diploid and
      aneuploid patterns, 3 cases (11%) had a combination of tetraploid and aneuploid
      patterns, and 2 cases had two aneuploid stem lines. The relationship between DNA
      ploidy pattern and tumor histologic and cytologic morphology was also examined.
      CONCLUSION: There is a high incidence of DNA content heterogeneity in NPC. The
      relevance of tumor heterogeneity to the biologic behavior of NPC awaits further
      study. DNA quantification with image cytometry on destained cytologic
      preparations is feasible and reliable.

PMID- 11444192
TI  - Computerized image analysis of Ki-67 in ductal breast carcinoma in situ.
AB  - OBJECTIVE: To develop and determine the staining protocols and computerized image
      analysis methods that are the most effective combination for performing
      quantitative analysis of Ki-67. STUDY DESIGN: We compared conventional bright
      field light microscopy and refractive optical enhancement methods in combination
      with various immunodetection and filter enhancement methods, including immunogold
      in combination with epipolarization refractive optics and enzymatic conversion of
      chromogenic substrates in combination with optical filter enhancement. Initial Ki
      67 tests were performed on lymph node tissues and cultured human breast cells and
      then applied to 200 ductal carcinoma in situ (DCIS) samples. DCIS acini were
      digitally acquired, and a region of interest was manually outlined in each one
      with a digital stylus to include only the cellular component; then the Ki-67
      staining index was quantified by segmentation analysis. RESULTS: Although
      combining epipolarization analysis with immunohistogold staining was the most
      sensitive detection method, nonspecific binding was too high. The streptavidin
      horseradish-peroxidase enzymatic conversion of 3,3'-diaminobenzidine (DAB) in
      combination with optical enhancement filters was the most effective method
      tested. Ki-67 stain was associated with dense fibrillar structures of the
      nucleoli in the less intensely staining nuclei and was most intense in paired
      nuclei. CONCLUSION: The method of measuring Ki-67 expression by DAB staining
      combined with optical enhancement filters and quantification via computer
      assisted image analysis techniques produced objective and reproducible results.
      As such, this method can offer (1) less intraobserver and interobserver
      variability, (2) a digital archival record, and (3) a baseline for digital
      exchange of information between studies.

PMID- 11444193
TI  - Cyclin A and Ki-67 with DNA content in benign and malignant prostatic epithelial
      lesions.
AB  - OBJECTIVE: To evaluate the usefulness of immunohistochemical staining of cyclin A
      and Ki-67 together with DNA content in the classification of benign prostatic
      hyperplasia, prostatic intraepithelial neoplasm (PIN) and prostatic carcinoma
      foci and to compare these parameters with each other and with parameters obtained
      from conventional histopathology. STUDY DESIGN: We selected 37 carcinoma, 18 PIN
      and 8 hyperplastic foci from prostatectomies done during 1996 and 1997 at Turku
      University Central Hospital. Cyclin A and Ki-67 staining was assessed by
      immunohistochemistry and DNA content by image cytometry. RESULTS: The
      hyperplastic, PIN and carcinoma foci differed clearly in their 2.5c exceeding
      rates, image cytometric proliferation indices and staining indices for cyclin A
      and Ki-67. No significant differences were found between these histologic
      entities in their modal DNA ploidy values. In carcinomas, cyclin A and Ki-67
      indices differed between low, intermediate and high Gleason and World Health
      Organization grading groups. Diploid and tetraploid carcinomas had similar cyclin
      A and Ki-67 indices, which differed from those of aneuploid carcinomas.
      CONCLUSION: The 2.5c exceeding rate and image cytometric proliferation index as
      well as the cyclin A and Ki-67 indices differed significantly between different
      types of prostatic lesions. Cyclin A and Ki-67 had good correlations with the
      histologic grade of carcinoma.

PMID- 11444194
TI  - Prognostic value of DNA flow cytometry in sympathoadrenal paragangliomas.
AB  - OBJECTIVE: To determine whether ploidy patterns are related to prognosis in
      sympathoadrenal paragangliomas (SAP) using flow cytometry. STUDY DESIGN: DNA flow
      cytometric analysis of formalin-fixed, paraffin-embedded tumor samples from 36
      patients with SAP was performed. Eight cases fulfilled at least one of the
      following malignancy criteria: (1) extensive invasion of adjacent structures (5
      cases), (2) local recurrence (3 cases), or (3) metastases (4 cases). RESULTS: Of
      the 36 tumors, 22 (61%) showed nondiploid patterns (12 aneuploid, 10 tetraploid).
      All diploid tumors were benign, while all malignant cases showed nondiploid
      patterns (P = .0131). The differences between diploid and aneuploid tumors and
      between diploid and tetraploid tumors, with regard to the malignancy of the
      disease, were statistically significant (P = .03311 and .01976, respectively).
      Only one malignant tumor had a DNA index < 1.75 (P = .00259). CONCLUSION:
      Anomalous DNA ploidy patterns are frequent in SAP, without necessarily implying
      malignancy. However, diploid DNA content may be a marker of a good prognosis. The
      likelihood of malignancy is greater in the tetraploid and peritetraploid range.

PMID- 11444195
TI  - Early uterine serous carcinoma: clonal origin of extrauterine disease.
AB  - Uterine serous carcinoma (USC) is an uncommon but aggressive type of endometrial
      carcinoma that is frequently associated with extrauterine disease despite minimal
      or no myometrial invasion. The origin of the extrauterine tumors in this setting
      remains controversial. The majority of USCs (90%) and endometrial intraepithelial
      carcinomas (78%), the putative precursor of USC, have p53 mutations, suggesting
      that p53 alterations occur early in the pathogenesis of USC. To determine if the
      extrauterine tumors associated with minimally invasive USC and endometrial
      intraepithelial carcinoma (EIC) represent metastases or multifocal primary
      tumors, we examined the mutational pattern of the p53 gene in 3 cases of
      minimally invasive USC and 1 case of EIC and in the corresponding extrauterine
      tumors associated with each of the cases. In all 4 cases, the primary tumors and
      the associated extrauterine tumor foci had identical p53 mutations. Our results
      support the premise that extrauterine serous tumors found in association with EIC
      or minimally invasive USC represent a unifocal process and thus are early
      metastases.

PMID- 11444196
TI  - Immunohistochemical expression of gastric mucin and p53 in minimal deviation
      adenocarcinoma of the uterine cervix.
AB  - Comparative immunostaining with antibodies against gastric mucin and p53 was
      performed on 6 cases of minimal deviation adenocarcinoma (MDA) of the uterine
      cervix. The MDAs consisted of predominant areas of glands lined by extremely well
      differentiated tall columnar epithelial cells with little cytological atypia and
      minor foci of less well-differentiated glandular epithelium with a minor degree
      of nuclear atypia. Immunostaining for gastric mucin with a monoclonal antibody
      HIK1083 revealed that all the tumors areas of typical MDA were partly
      immunoreactive for HIK1083, but the coexisting less well-differentiated glands
      were essentially negative. Four MDAs focally contained cells with p53 positive
      nuclei that were located exclusively in the less well-differentiated cells that
      lacked gastric mucin. In the pelvic lymph nodes in 2 cases, most of the
      metastatic tumor was less differentiated and a positive reaction for HIK1083 was
      observed only in small foci of typical MDA. No significant overexpression of p53
      was observed in the metastases. Immunohistochemical expression of gastric mucin
      and p53 may be related to the histological differentiation of MDA, and detection
      of p53 overexpression may help to identify critical steps in the local
      progression of MDA.

PMID- 11444197
TI  - Demonstration of focal p53 expression without genetic alterations in
      endometriotic lesions.
AB  - Their monoclonal origin (as indicated by recent investigations) indicates the
      neoplastic nature of most endometriotic lesions. p53, a representative tumor
      suppressor, regulates cell proliferation, and genetic alterations in p53 are
      involved in carcinogenesis in a wide variety of human cancers. The aim of this
      study was to examine endometriotic lesions for p53 expression and genetic
      alterations in p53. An immunohistochemical study revealed that 20% (13/64) of
      endometriotic lesions showed focal p53 expression in the epithelial cells. Using
      serial paraffin sections, we employed a microdissection method to extract DNA
      from the endometriotic tissues that showed p53 expression. No mutations were
      found in exons 5-8 in p53 by cleavase fragment length polymorphism scanning and
      polymerase chain reaction-DNA sequencing. Moreover, neither loss of
      heterozygosity nor microsatellite instability was detected at the microsatellite
      marker sites of p53. These results suggest that the focal p53 expression
      recognized in the endometriotic epithelia may be due to overproduction of wild
      type p53 protein.

PMID- 11444198
TI  - Alpha-smooth muscle actin-positive myofibroblasts in endometrial stroma are not a
      reliable criterion for the diagnosis of well differentiated endometrioid
      adenocarcinoma in small tissue samples.
AB  - Although a desmoplastic stromal reaction in well-differentiated endometrioid
      adenocarcinoma is considered a major criterion in the differential diagnosis with
      atypical hyperplasia, this histologic feature has not met with universal
      approval. Since alpha-smooth muscle (alpha-SM) actin positive myofibroblasts
      characterize the desmoplastic stromal response in a variety of neoplasms, the
      present study was undertaken in order to establish whether these cells are also
      prominent in the stroma of endometrioid carcinoma and if present could be used as
      a valid criterion in the differential diagnosis between benign and malignant
      lesions. The present study of 100 endometrial samples showed focal desmoplastic
      stromal reaction with alpha-SM actin positive myofibroblasts in 30% of small
      samples and in 50% of hysterectomy specimens with endometrioid carcinoma. In
      normal endometrium and in benign lesions lacking a desmoplastic reaction, focal
      stromal alpha-SM actin positivity was a very common finding. Stromal alpha-SM
      actin-positive cells were also frequently seen in nondesmoplastic stroma of
      endometrioid carcinoma. Thus the common presence of alpha-SM actin-positive
      myofibroblasts in normal endometrial stroma and in benign and malignant lesions
      precludes its usefulness in the diagnosis of well differentiated endometrioid
      adenocarcinoma, especially in small tissue samples.

PMID- 11444199
TI  - Uterine leiomyomas with Eosinophils: a clinicopathologic study of 3 cases.
AB  - Although leiomyomas (LMs) of the uterus are common, hematopoietic components
      within these tumors are not. Lymphoid and other hematopoietic elements have been
      previously recognized, but eosinophilic infiltrates in LMs have received little
      attention in the literature. The clinical and pathologic features of 3 cases of
      uterine LM with eosinophilic infiltration were studied. The patients ranged in
      age from 35 to 62 years and presented with abdominal and/or pelvic pain and
      abnormal uterine bleeding. None had peripheral blood eosinophilia or clinical
      evidence of allergy or parasitic infection. One patient had a benign LM, and the
      other 2 patients had smooth muscle tumors of uncertain malignant potential. The
      tumors contained variable numbers of eosinophils and Giemsa stains showed
      variable numbers of mast cells in addition to the eosinophils. We also performed
      immunohistochemical and in situ hybridization studies to assess for interleukin-5
      (IL-5) and eotaxin in these LMs. There was no consistent association between the
      presence of eosinophils and either IL-5 or eotaxin in smooth muscle cells,
      suggesting that mechanisms other than IL-5 or eotaxin production may account for
      the eosinophilia. Because eosinophils are believed to be involved in wound
      healing, tissue remodeling, and fibrosis, their presence within LMs may reflect a
      response to tissue injury produced by the neoplasm rather than intrinsic
      recruitment by chemotactic factors produced by the smooth muscle cells. Their
      presence, however, does not appear to have any clinical significance.

PMID- 11444200
TI  - k-ras mutation may be an early event in mucinous ovarian tumorigenesis.
AB  - We explored the possible pathogenetic pathway for mucinous ovarian tumorigenesis
      by examining the k-ras mutational patterns in ovarian mucinous tumors (OMTs) with
      benign, borderline, and invasive epithelium in which the different types of
      mucinous epithelium are in close proximity. Sixteen patients with ovarian
      mucinous borderline tumors (OMBTs) and 4 patients with grade 1 ovarian mucinous
      adenocarcinomas (OMCs) were selected for the presence of a single histologic
      section which contained a clear "transition" zone from benign mucinous epithelium
      to borderline mucinous epithelium, and in four cases, to invasive epithelium. A
      PixCell II Laser Capture Microscope was used to microdissect and retrieve benign,
      borderline, and invasive epithelium separately from the 20 OMTs. Normal ovarian
      stroma from the same histologic section in each case was also microdissected and
      retrieved for use as a control. k-ras mutations were detected in these samples by
      PCR-SSCP analysis followed by direct PCR cycle sequencing. k-ras mutations were
      found in 8/16 (50%) of the OMBTs and 2/4 (50%) of the grade 1 OMCs. In 6 of these
      10 cases (4 in OMBTs, 2 in grade 1 OMCs), the same k-ras mutation was found in
      both the benign and borderline (and invasive) regions. In 3 cases in which k-ras
      mutations were identified, the mutation was found in either the benign or
      borderline tissue samples alone, and in one case, two distinct mutations were
      found. No k-ras mutations were identified in the normal ovarian stroma. The
      presence of a k-ras mutation in adjacent benign and borderline regions of a
      single OMT may suggest a progression in the development of OMTs from benign to
      borderline and grade 1 OMCs. k-ras mutations, when they occur, are likely early
      genetic changes but may not alone be sufficient for malignant transformation of
      ovarian epithelium.

PMID- 11444201
TI  - Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract.
AB  - Clear cell carcinoma of the gynecologic tract has been defined in terms of its
      clinical and histologic features; however, its immunophenotypic profile has not
      been fully characterized. Seventeen cases of primary clear cell carcinoma from
      various sites within the female genital tract (11 ovary, 5 uterus, 1 vagina) were
      analyzed by immunohistochemistry. These tumors were assessed for the expression
      of cytokeratin 7 (CK7), cytokeratin 20 (CK20), low and high molecular weight
      cytokeratin, (CAM5.2 and 34 beta E12, respectively), carcinoembryonic antigen
      (CEA), Leu-M1, vimentin, estrogen receptor (ER), progesterone receptor (PR), bcl
      2, p53, HER-2/neu, and CA-125. The characteristic immunoprofile for all sites was
      positivity for CK7, CAM5.2, 34 beta E12, CEA, Leu-M1, vimentin, bcl-2, p53, and
      CA-125; variably positivity for ER and HER-2/neu; and negativity for CK20 and PR.
      For comparison, two cases of urologic clear cell carcinoma (1 bladder, 1 urethra)
      were also studied, and their profile was found to be similar to the gynecologic
      cases. Aside from minor differences, clear cell carcinoma appears to have the
      same immunophenotype regardless of whether it originates in the endometrium,
      ovary, or genitourinary tract. Much of its profile is similar to other
      gynecologic adenocarcinomas, but some of the markers studied may be useful in the
      differential diagnosis of this tumor.

PMID- 11444202
TI  - Immunohistochemical distribution of tumor-associated antigen CA6 in gynecological
      neoplasms as detected by monoclonal antibody DS6.
AB  - DS6 is a murine monoclonal antibody developed using ovarian papillary serous
      adenocarcinoma as the immunogen. DS6 immunohistochemically reacts with a tumor
      associated antigen, CA6, which has a limited range of expression in normal human
      tissues and is not expressed by benign mesothelium. We have studied the spectrum
      of immunohistochemical reactivity of antibody DS6 in 293 formalin-fixed, paraffin
      embedded human gynecological neoplasms. The CA6 antigen shows strong expression
      in serous adenocarcinomas of the ovary (56/58 cases) and endometrium (6/6). CA6
      is also expressed by the majority of ovarian endometrioid adenocarcinomas and
      Brenner tumors and by the majority of endometrioid adenocarcinomas, mucinous
      adenocarcinomas, and clear cell adenocarcinomas of the endometrium. CA6 is
      detected in 14% of ovarian clear cell carcinomas and is not detected in ovarian
      mucinous cystadenomas (0/7), mucinous intestinal-type borderline tumors (0/8),
      mucinous adenocarcinomas (0/10), or in malignant mesotheliomas (0/8). In
      neoplasms with papillary or glandular growth patterns, CA6 is detected along
      luminal cell membranes. CA6 is also seen along peripheral cell membranes and
      focally in the cytoplasm in some epithelial neoplasms. There is heterogeneity in
      immunohistochemical staining for DS6 both within an individual neoplasm and
      between neoplasms. Reactivity is not detected in neoplasms of sex cord-stromal,
      mesenchymal or germ cell origin.

PMID- 11444203
TI  - Ovarian endometriosis and clear cell carcinoma, leiomyomatosis peritonealis
      disseminata, and endometrial adenocarcinoma: an unusual, pathogenetically related
      association.
AB  - A 42 year-old female with a preoperative clinical diagnosis of ovarian cancer
      underwent laparotomy which revealed leiomyomatosis peritonealis disseminata (LPD)
      in the peritoneum and omentum and a left ovarian endometriotic cyst associated
      with a clear cell carcinoma. A grade 1, superfically invasive villoglandular
      endometrial endometrioid adenocarcinoma was also found. Microscopically, the
      endometriotic cyst wall contained an extensive peripheral band-like condensation
      of stromal cells. These cells were strongly positive for alpha inhibin and may
      have been the hormonal source responsible for the induction of the simultaneous
      LPD and endometrial adenocarcinoma. It is proposed that endometriosis is not only
      a precursor of clear cell carcinoma but, through secondary hormonal induction of
      the surrounding ovarian stroma, may also provide a hormonal stimulus for diverse
      proliferative processes.

PMID- 11444204
TI  - Recurrent atypical myxoid fibroepithelial polyp associated with vulvar Crohn's
      disease.
AB  - Fibroepithelial polyps of the lower female genital tract are common lesions that
      can rarely exhibit atypical features including increased and atypical mitoses,
      bizarre nuclei, and hypercellularity, a combination of findings that may suggest
      malignancy. Five recurrent cases have been published to date, two of which were
      in pregnant females; the other three followed incomplete excisions. Our case is
      that of a 25-year-old female with Crohn's disease who developed multiple
      recurrences of polypoid and domed lesions of the labium minus following surgical
      excision. Histologic findings in the initial and recurrent lesions were
      consistent with atypical myxoid fibroepithelial polyps with underlying vulvar
      Crohn's disease. The lesions subsequently improved with standard Crohn's
      treatment including 5-amino-salicylic acid (Pentasa) and prednisone. The present
      case represents the only example of this entity associated with Crohn's disease,
      and it is the only reported recurrent case not associated with pregnancy,
      tamoxifen administration, or positive excision margins. The clinical,
      microscopic, and immunohistochemical findings of this case suggest that atypical
      fibroepithelial polyps of the lower female genital tract, cutaneous pleomorphic
      fibroma, and lesions such as fibroepithelial polyps of the anus may represent
      variants of the same atypical reparative process.

PMID- 11444205
TI  - Intraplacental smooth muscle tumor: a case report.
AB  - We present the second reported case of a smooth muscle neoplasm involving the
      placental parenchyma. On gross examination, the tumor easily separated from the
      uterus and had a whorled cut surface with finger-like extensions into the villous
      parenchyma, very similar to the previously described case. The differential
      diagnosis included a primary smooth muscle tumor of the placenta (placental
      leiomyoma), a primary uterine neoplasm incorporated into the placenta, and a
      metastatic sarcoma. In this case, the infant was male, and the polymerase chain
      reaction technique demonstrated the presence of Y chromosome gene in the
      placental parenchyma and its absence in the placental neoplasm. Thus, this
      neoplasm, despite its gross appearance of a primary placental tumor, actually
      represented an incorporated benign uterine leiomyoma.

PMID- 11444206
TI  - History of gynecological pathology. X. Dr. Robert Meyer.

PMID- 11444207
TI  - Large cell neuroendocrine carcinoma of the cervix associated with adenocarcinoma
      in situ: evidence of a common origin.

PMID- 11444208
TI  - [Time management: realities for parents living with children with motor
      deficiencies].
AB  - A quantitative study involving 244 families from three health and social service
      regions of Quebec was undertaken to explore how families function. Fourteen
      families agreed to participate in the qualitative part of this study. Twenty
      eight parents participated through an in-depth interview. During the interviews,
      the impact of the presence of a child with a motor disability on the parents' use
      of time was discussed. An analysis of the themes and categories highlighted the
      different aspects of the impact of a handicapped child on the parents' use of
      time in relation to the four spheres of life. In fact, the parents that were
      interviewed indicated that the presence of their child greatly influenced the
      time they had available for their personal, conjugal and family life as well as
      for doing any paid work. In general, mothers devoted more time than fathers to
      the care of the child. This situation has a direct impact on the way the mothers
      manage their time. Based on an analysis of the respondents' comments, the author
      recommends to offer support to the parents in order to assist them with time
      management.

PMID- 11444209
TI  - An unlikely savior. Consultant tries to save rural Ga. county hospital.

PMID- 11444210
TI  - A college rescues Ohio hospital.

PMID- 11444211
TI  - Enhancing the baccalaureate's value.

PMID- 11444212
TI  - Plasmid biology 2000: international symposium on molecular biology of bacterial
      plasmids. Prague, Czech Republic, September 19-25, 2000. Abstracts.

PMID- 11444213
TI  - [Problems associated with the National Health Insurance coverage for nursing].

PMID- 11444214
TI  - [Current status and the future prospects of guidelines for the care of
      psychiatric patients].

PMID- 11444216
TI  - 8th International Conference on Wilson Disease and Menkes Disease. Leipzig,
      Germany, April 16-18, 2001. Abstracts.

PMID- 11444215
TI  - 4th Decennial International Conference on Nosocomial and Healthcare-Associated
      Infections. March 5-9, 2000, Atlanta, Georgia. Proceedings.

PMID- 11444217
TI  - The newborn at high risk of brain damage. EURope Against Infant Brain Injury
      (EURAIBI) international workshop. Siena, Italy, April 5-7, 2001. Proceedings.

PMID- 11444219
TI  - ASGE (American Society for Gastrointestinal Endoscopy) meeting. May 20-23, 2001,
      Atlanta, Georgia. Program and abstracts.

PMID- 11444218
TI  - Innate immune trouble detectors.

PMID- 11444220
TI  - The Royal Society of Medicine in Ireland. Section and society meetings 1995-1999.
      Abstracts.

PMID- 11444221
TI  - Abstracts of the 8th International Congress on Schizophrenia Research. British
      Columbia, Canada, April 28-May 2, 2001.

PMID- 11444222
TI  - 11th European Congress of Clinical Microbiology and Infectious Diseases.
      Istanbul, Turkey, 1-4 April 2001. Abstracts.

PMID- 11444223
TI  - Proceedings of SCANNING 2001. May 5-7, 2001, New York, New York, USA. Abstracts.

PMID- 11444224
TI  - 11th meeting of the European Neurological Society. 21-25 April, 2001, Paris,
      France. Abstracts.

PMID- 11444225
TI  - 49th ASMS conference on mass spectrometry and allied topics. May 27-31, 2001,
      Chicago, Illinois. Program.

PMID- 11444226
TI  - [Entire or cervix neck ablation of the uterus].

PMID- 11444227
TI  - Neonatal screening in the 21st century. Proceedings of the 3rd Asia-Pacific
      regional meeting of the International Society for Neonatal Screening. November 15
      18, 1998, Chiang Mai, Thailand.

PMID- 11444228
TI  - Neurological complications of cervical spine manipulation.

PMID- 11444229
TI  - The Good Soldier Svejk syndrome.

PMID- 11444230
TI  - Service-profit chain: the new economics of service.

PMID- 11444231
TI  - One amino acid residue cannot determine the differences in the catalytic and
      regulatory properties of monoamine oxidases A and B.

PMID- 11444232
TI  - Data dilemmas. Standardization urged for Calif.'s Medi-Cal providers.

PMID- 11444233
TI  - Measurement of the stiffness of endoscopes - a plea for commonality.

PMID- 11444234
TI  - Research outcomes in British gastroenterology: an audit of the subsequent full
      publication of abstracts presented at the British Society of Gastroenterology.

PMID- 11444235
TI  - Leptin in the human stomach.

PMID- 11444236
TI  - Histological and genetic heterogeneity in synchronous hepatocellular carcinoma.

PMID- 11444237
TI  - Phenotypic expression of the HFE gene mutation (C282Y) among the hospitalised
      population.

PMID- 11444238
TI  - The African enigma: the parasite's perspective.

PMID- 11444241
TI  - Current reading in nuclear medicine.

PMID- 11444240
TI  - Guidelines for the management of iron deficiency anaemia.

PMID- 11444242
TI  - Trying to keep "mad cow disease" out of U.S. herds.

PMID- 11444243
TI  - Highlights of FDA food safety efforts: fruit juice, mercury in fish.

PMID- 11444244
TI  - The power of Accutane. The benefits and risks of a breakthrough acne drug.

PMID- 11444245
TI  - Frances Oldham Kelsey. FDA medical reviewer leaves her mark on history.

PMID- 11444246
TI  - Grappling with the quality of life. Patients, FDA and drug companies struggle to
      link therapies with well-being.

PMID- 11444247
TI  - Online laetrile vendor ordered to shut down.

PMID- 11444248
TI  - Company gets a guilty reading in glucose monitor case.

PMID- 11444249
TI  - Court orders refund to purchasers of gas grill igniters.

PMID- 11444250
TI  - Living in a world with thalidomide: a dose of reality.

PMID- 11444251
TI  - Making medical progress. A look at FDA approvals in 2000.

PMID- 11444252
TI  - Proposed rules issued for bioengineered foods.

PMID- 11444253
TI  - Review of two phase III randomized trials of single-agent docetaxel in previously
      treated advanced non--small cell lung cancer.
AB  - Randomized phase III studies reported this year prove that docetaxel is superior
      both to best supportive care (BSC) and to a standard regimen of vinorelbine or
      ifosfamide as second-line therapy for advanced non--small cell lung cancer. In a
      landmark study authored by Dr Frances Shepherd, 204 patients with stage IIIB/IV
      non--small cell lung cancer who had failed previous cisplatin-based chemotherapy
      were randomized to receive either docetaxel (100 mg/m(2) or 75 mg/m(2) every 3
      weeks) or BSC. The median survival of patients assigned to docetaxel was 7.6
      months, significantly longer than the median of 4.6 months in patients treated
      with BSC alone. The rate of febrile neutropenia was 22% in patients receiving 100
      mg/m(2) docetaxel but only 1.8% when the dose was 75 mg/m(2). Patients treated
      with docetaxel required less additional opioid analgesia and palliative
      radiotherapy than those receiving BSC. Patients in the docetaxel 75 mg/m(2) arm
      also were significantly less likely to lose 10% or more body weight and to
      experience severe fatigue. In a second phase III study led by Dr Frank Fossella,
      373 patients were randomized to docetaxel 100 mg/m(2), docetaxel 75 mg/m(2), or a
      control arm of vinorelbine 30 mg/m(2) or ifosfamide 2 g/m(2). Median survival was
      similar between the two groups (range, 5.5 to 5.7 months). However, the survival
      rate at I year was significantly higher in patients assigned to 75 mg/m(2) than
      in the control arm. Patients receiving docetaxel 75 mg/m(2) experienced better
      global quality of life (Lung Cancer Symptom Scale: patient-rated) than patients
      receiving vinorelbine or ifosfamide. A higher incidence of grade 4 neutropenia
      and febrile neutropenia was observed in the docetaxel arms of the study, but the
      incidence of infections was low and nonhematologic toxicities were similar across
      all treatment arms. These studies show docetaxel provides meaningful survival and
      clinical benefits in second-line non-small cell lung cancer. The dose recommended
      in this setting is 75 mg/m(2) every 3 weeks.

PMID- 11444254
TI  - [The experimental study of the anti-enterovirus effects of drugs in vitro].
AB  - OBJECTIVE: To screen the safe and effective anti-enterovirus drugs for clinical
      application. METHODS: The cytotoxicity of Ribavirin, Shuanghuanglian and Garlic
      were evaluated through MTT colorimetry and cell morphology. The antiviral
      activity of Ribavirin, Shuanghuanglian and Garlic were studied in HEL and Vero
      cells infected with CBV3 and ECHO11 by observing cytopathic effect (CPE), MTT
      colorimetry and plaque-reduction assay. The antiviral activity of these three
      drugs were compared and that of Shuanghuanglian and Garlic were also compared
      before and after ECHO11 absorbing by plaque-reduction assay. RESULTS: (1) The
      cytotoxicity of these three drugs were expressed as TC50(50% toxic
      concentration). TC50 of Ribavirin was 2 mg/ml, of Shuanghuanglian 5 mg/ml, of
      Garlic 12.5 micrograms/ml. (2) Ribavirin could inhibit CBV3 and ECHO11 at the
      concentration ranged from 1 mg/ml to 1.5 mg/ml. Shuanghuanglian could inhibit
      CBV3 and ECHO11 at the concentration of 0.5 mg/ml and the viral inhibiting effect
      was concentration-dependent. Garlic could inhibit CBV3 and ECHO11 at the
      concentration ranged from 2.5 micrograms/ml to 7.5 micrograms/ml and 5
      micrograms/ml was the most effective. (3) Plaque-reduction assay was used to test
      the anti-virus (CBV3 and ECHO11) activity of these three drugs: plaque reduction
      rate of 1.5 mg/ml Ribavirin was 43.2% and 37.2%, of 2.5 mg/ml Shuanghuanglian was
      81.1% and 88.4% and of 5 micrograms/ml Garlic was 66.2% and 77.4% respectively.
      The plaque reduction rate of Ribavirin was lower than the other two drugs (P <
      0.05), between these two showed no significant difference (P > 0.05). The anti
      ECHO11 activity of Shanghuanglian before ECHO11 adsorbing was higher than after
      ECHO11 adsorbing (P < 0.05). There was no significant difference between the
      plaque reduction rates of Garlic before and after ECHO11 adsorbin. CONCLUSION:
      All of the three drugs have anti-virus activity in vitro while Shuanghuanglian
      and Garlic are more effective. Among these three drugs, the cytotoxicity of
      Shuanghuanglian is the most weak and the anti-virus activity is the strongest.
      The antiviral activity of Shuanghuanglian adding before virus adsorbing was
      higher, so it seems that Shuanghuanglian can prevent EV infection.

PMID- 11444255
TI  - Cases from the aerospace medicine residents' teaching file. Decompression
      sickness.
AB  - Decompression sickness is an uncommon but serious risk associated with flying and
      SCUBA diving with potential for significant morbidity and mortality. It can occur
      in both novice and experienced individuals. This case illustrates an atypical
      presentation of decompression sickness in an experienced amateur SCUBA diver.
      Clinical suspicion must be high, since the presenting symptoms can be nonspecific
      as in this case. Early recognition and treatment are important for maximum
      recovery.

PMID- 11444256
TI  - Effect of sulfosulfuron on the urine and urothelium of male rats.
AB  - Sulfosulfuron, developed as a herbicide, caused increased microcrystalluria and
      the formation of urinary tract calculi when fed to male and female rats in a
      chronic 2-year study at doses of 5,000 ppm and 20,000 ppm. Hyperplasia was also
      seen in urinary bladders at 5,000 ppm and 20,000 ppm, almost exclusively in the
      presence of observable calculi/microcalculi. Urinary bladder tumors were found in
      2 females in the 5000 ppm group, both in the presence of calculi. No increased
      microcrystalluria, calculi, or tumors were found at doses of 500 ppm and lower.
      In the current study, 5 groups of male Sprague-Dawley rats were fed sulfosulfuron
      at doses of 50, 500, 5,000, and 20,000 ppm for 10 weeks. Ten animals were co
      administered 5,000 ppm sulfosulfuron with 12,300 ppm NH4Cl to determine if
      inhibition of the formation of calculi would prevent any urothelial effects of
      treatment with sulfosulfuron. Ten animals in the control group and in the high
      dose sulfosulfuron group were fed only basal diet for an additional 10 weeks to
      determine if the effects of sulfosulfuron on the bladder epithelium were
      reversible. There was an increased incidence of microcrystalluria observed at
      5,000 and 20,000 ppm. There was no increase in microcrystalluria observed in the
      urine of rats co-administered sulfosulfuron and NH4Cl. Urinary bladder calculi
      were found in the bladder of 1 animal fed 20,000 ppm. Examination by light
      microscopy showed diffuse papillary/nodular hyperplasia of the bladder epithelium
      in this animal. No increased microcrystalluria was observed after withdrawal of
      the chemical from the diet and the bladder epithelium was normal by light
      microscopy. The hyperplastic effects associated with the feeding of high doses of
      sulfosulfuron occur only with the appearance of urinary tract calculi. Based on
      these results and anatomical differences between rats and humans, it may be
      concluded that the hyperplastic and carcinogenic effects of sulfosulfuron in rats
      are high-dose, threshold phenomena that are not likely to occur in humans under
      environmentally relevant exposures.

PMID- 11444257
TI  - Neuropsychiatric assessment of Alzheimer's disease and related dementias.
AB  - Alzheimer's disease (AD) patients exhibit a variety of behavioral alterations
      including agitation, apathy, depression, anxiety, delusions, irritability and
      disinhibition. Most patients with AD exhibit neuropsychiatric symptoms, and
      behavioral changes become more frequent with advancing disease severity. The NPI
      is a valid and reliable means of assessing neuropsychiatric symptoms in patients
      with dementia. The NPI correlates with increasing disability in activities of
      daily living and increasing cognitive impairment. Physical illness contributes
      little to behavioral symptoms measured by the NPI. Reduced frontal lobe
      metabolism and perfusion have been identified in patients with apathy, agitation,
      psychosis and depression. Patients with elevated agitation scores on the NPI have
      a higher burden of frontal lobe neurofibrillary tangles than patients without
      agitation. The NPI is sensitive to behavioral improvements following treatment
      with cholinesterase inhibitors and psychotropic agents. Neuropsychiatric symptom
      profiles differ among dementia syndromes, and the NPI provides a means of
      assessing neuropsychiatric symptoms that may aid in differential diagnosis.
      Evaluation of neuropsychiatric symptoms is a critical aspect of dementia
      diagnosis and management.

PMID- 11444258
TI  - Incidence, prevalence and the rates of cutaneous reactions to drugs.

PMID- 11444259
TI  - What's new in psoriasis.

PMID- 11444260
TI  - Atopic dermatitis and diet.

PMID- 11444261
TI  - Diet and atopic dermatitis.

PMID- 11444262
TI  - What's new in linear IgA disease?

PMID- 11444263
TI  - Drug-induced photosensitivity with antimycotics.

PMID- 11444264
TI  - Photosensitivity induced by oral itraconazole.

PMID- 11444265
TI  - How to treat oral leucoplakia.

PMID- 11444266
TI  - Oral pigmentation.
AB  - Oral pigmentation may be physiological or pathological in nature. It may
      represent a localized anomaly of limited significance or the presentation of
      potentially life-threatening multisystem disease. Evaluation of a patient with
      oral pigmentation requires a systematic approach with resource to appropriate
      investigations in certain circumstances. A full history of evolution of the
      pigmentary changes, as well as inquiring into family history, drug ingestion and
      systemic symptoms of concurrent disease are clearly important in the assessment.
      The duration, pattern, hue and distribution of colour changes can provide useful
      diagnostic clues. Special attention is given to newly appearing lesions, or those
      that have changed significantly in appearance, and biopsy may be needed to
      validate the clinical impression. This review should enable the reader to
      increase their familiarity with the assessment of oral pigmentation, the common
      causes of oral pigmentary change and the rarer disorders of pigmentation seen in
      this area. The systemic diseases that may give rise to oral pigmentation are
      detailed and the early signs of oral melanoma are highlighted, as well as the
      drugs which may cause pigmentary changes in this area and the different pattern
      of pigmentation they may induce.

PMID- 11444267
TI  - The epidemiology of onychomycosis: possible role of smoking and peripheral
      arterial disease.
AB  - BACKGROUND: Onychomycosis is a relatively common condition the aetiology of which
      appears to be multifactorial, with both genetic and acquired factors being
      responsible. In our clinical practice we have observed that smokers and
      individuals with peripheral arterial disease may have an increased prevalence of
      onychomycosis compared to normal individuals. PATIENTS AND METHODS: Patients
      attending a vascular clinic in a hospital were asked about a history of smoking
      and peripheral arterial disease. The lower extremity was assessed for peripheral
      arterial disease. Material was obtained from toenails for mycological evaluation.
      RESULTS: Two hundred and fifty-four patients (male 146, female 108; age, mean +/-
      standard error, 66.6 +/- 0.8 years) were enrolled. Abnormal-appearing nails and
      onychomycosis were present in 49.2% and 22.4% of patients, respectively. Factors
      associated with onychomycosis included, increasing age (risk odds ratio [ROR]
      1.05, P = 0.002), male gender (ROR 1.7, P = 0.09), smoking (packs per day) (ROR
      1.9, P = 0.02) and peripheral arterial disease (ROR 4.8, P = 0.02). CONCLUSIONS:
      The factors predisposing to the development of onychomycosis are multifactorial.
      Both smoking (number of packs of cigarettes consumed per day) and peripheral
      arterial disease are independent predictors of onychomycosis. Awareness of these
      factors may help in the prevention of onychomycosis and the optimal management of
      this disease.

PMID- 11444268
TI  - Melanoma screening: results of the first one-day campaign in Belgium ('melanoma
      Monday').
AB  - BACKGROUND: Although the incidence of melanoma is increasing and many informative
      campaigns have been organized. The general population is still little informed
      about this tumour. AIMS: To organize a media campaign, with more relevant
      information and the opportunity for free skin inspections. METHODS: A 'Task
      Force' organized a media campaign in April 1999 and convinced 65% of the Belgian
      dermatologists to give up 4 h of their time to do free skin examinations for skin
      cancer on Monday 26 April 1999; it was called 'Melanoma Monday'. RESULTS: A total
      2767 patients were screened. We found 25 melanomas and suspected 59 basal cell
      carcinomas. In the following 4 weeks another 141 melanomas were found. These 166
      melanomas found in one month represent 15-20% of the total number of melanomas
      per year in Belgium. SUMMARY: A media campaign with relevant information combined
      with screening opportunities can lead to the early detection of melanomas in a
      large number of patients and can continue to alert people at risk in the
      following weeks.

PMID- 11444269
TI  - Acitretin and treatment of the oral leucoplakias. A model to have an active
      molecules release.
AB  - AIMS: The aim of this study was to investigate the effectiveness of acitretin in
      a new topical formulation (mucoadhesive two-layer tablets) for the treatment of
      oral leucoplakias. METHODS: Twenty-one volunteers, 16 men, five women, with oral
      leucoplakia (histologically diagnosed), were included in this double-blind
      placebo-controlled study. Patients were randomized in three groups (A, B, C) of
      seven patients each. Groups A and B received tablets with different in vitro
      release profiles, and group C subjects (controls) received tablets without
      acitretin. The acitretin dose was 20 mg/day (two 10 mg tablets daily). Serum
      aspartate aminotransferase, alanine aminotransferase, cholesterol and
      triglycerides were evaluated before and after treatment. At the end of therapy
      the concentrations of acitretin in plasma, saliva and tissue were measured by
      high-performance liquid chromatography. RESULTS: At the end of the study 71%
      (groups A and B) of patients showed clinical remission or marked improvement. No
      improvement was noted in the control subjects (group C). These results were
      further confirmed by histological findings. There were no significant changes in
      laboratory values in the three groups. The acitretin concentration in plasma and
      tissue ranged from 0 to 50 mg with no difference between groups A and B, and it
      was very high in saliva (ranging from 4.9 to 43 mg) with higher concentrations in
      group A than in group B (due to a longer adhesion time in group A). Patients'
      compliance was excellent. The results show that mucoadhesive tablets of topical
      acitretin are efficacious in the treatment of oral leucoplakia without systemic
      side-effects.

PMID- 11444270
TI  - Second malignancies in melanoma patients in Thuringia.
AB  - OBJECTIVE: The incidence of melanoma is increasing. Melanoma patients are at risk
      for the development of second neoplasias. Data for the new German Bundeslander
      are not available, but would be suitable to define frequency, site and type of
      secondary malignancies and conclusions for follow-up of melanoma patients.
      DESIGN: Retrospective study at the Melanoma Outpatient Clinic of the Department
      of Dermatology and Allergology at the University of Jena (Germany) for patients
      seen between June 1966 and June 1999. To investigate the impact of second
      malignancies on survival a case-comparison study of mortality was performed. The
      log-rank test and chi2-test were used to investigate statistical significance.
      There were 554 patients with malignant melanoma, 237 male and 317 female, with an
      age at time of diagnosis between 17.0 and 90.1 years (mean 53.7 years). The mean
      follow-up was 5.6 years. RESULTS: Sixty-one patients (11.0%) developed a second
      tumour. The total number of tumours was 83. Forty-five patients developed one, 16
      developed > or = 2 second tumours. Basal cell carcinoma (BBC) was the most
      frequent neoplasia (17 patients, 22 tumours; mean age 64.9 years). A second
      melanoma was found in 15 patients, while two developed a third melanoma. The mean
      tumour thickness was 0.81 mm (in second or third melanomas) compared with 1.92 mm
      of primary melanomas. Seven female patients developed breast cancer (eight
      cancers; mean age 57.3 years). The other second tumours included skin cancer
      (eight), gastrointestinal tract tumours (four), genital cancers (19), brain
      tumours (two), lung cancer (two) and other tumours (six). The difference in
      survival of patients with second tumours was not statistically significant from
      age-, sex- and melanoma thickness-matched controls. CONCLUSIONS: Second
      malignancies were seen in 11.0% of melanoma patients. Most important are second
      skin tumours such as second melanomas and BCC, recommending follow-up by the
      dermatologist. In a group of patients with regular follow-up examinations, no
      negative impact of second tumours (BCC, melanoma, breast cancer) on overall
      survival could be detected.

PMID- 11444271
TI  - Topical cidofovir for severe cutaneous human papillomavirus and molluscum
      contagiosum infections in patients with HIV/AIDS. A pilot study.
AB  - BACKGROUND: Cidofovir is a nucleoside analogue of deoxycytidine with a strong
      activity against several DNA viruses, including herpes, pox and human papilloma
      virus (HPV). MATERIAL AND METHODS: Fourteen acquired immunodeficiency syndrome
      patients, 10 with extensive HPV lesions and four with molluscum contagiosum (MC)
      infections, unresponsive to conventional therapies, were treated with a cream
      containing cidofovir 1%. All the subjects had been on treatment with highly
      active antiretroviral therapy for almost 1 year before starting the cream.
      Measured end-points of therapy were efficacy, tolerability, side-effects and
      freedom from recurrence. RESULTS: Thirteen of the 14 patients (92.8%) completed
      the therapy, one dropped out. These 13 eventually cleared their MC or warts, over
      varying periods of time. In nine, the lesions regressed 2 weeks from the end of
      the first cycle of therapy. Three patients needed two cycles and the last three
      consecutive courses of topical therapy before the cutaneous lesions healed. No
      recurrence was observed in nine patients over an average follow-up period of 24.1
      months (range 12-30 months). Four patients had isolated relapses, which were
      successfully treated with simple curettage. SIDE-EFFECTS: All the patients
      experienced side-effects where they applied the cream. Inflammation, erosion and
      a burning sensation were the most frequent. Postinflammatory hyperpigmentation
      was observed in six cases, while two developed a transient alopecia on the beard
      area. No systemic side-effects or alteration of laboratory data were noted.
      CONCLUSION: Cidofovir appears to offer an effective therapeutic alternative
      option for lesions that are unresponsive to conventional methods. Appropriate
      clinical trials are required, however, to confirm the true efficacy and safety of
      topical cidofovir.

PMID- 11444272
TI  - Dermatological symptoms and sexual abuse: a review and case reports.
AB  - Dermatological symptoms in cases of sexual abuse can be very diverse. To
      establish a causal relationship between skin diseases and sexual abuse is
      particularly difficult. In dermatology, three main areas of presentation can be
      identified. ACUTE CONSEQUENCES: Direct injuries found on the genitalia and body.
      Behaviour and psychological changes seen. Sexually transmitted diseases (STD) may
      be identified, after an appropriate incubation period. LONG-TERM CONSEQUENCES: In
      the long term, even decades later, patients may manifest with a wide spectrum of
      psychosomatic manifestations of skin diseases, particularly factitious disorders.
      IMITATIONS: A group whose skin manifestations may mimic and be mistaken for
      sexual abuse. The initial suspicion of sexual abuse and the need for specific
      questioning and investigations can lead to a disturbance in the doctor-patient
      relationship.

PMID- 11444273
TI  - Circle hairs: a clinical curiosity.
AB  - A case of circle hairs is reported and the literature on the subject reviewed.
      Differential diagnoses are discussed as well as some theories on the nature of
      circle hairs.

PMID- 11444274
TI  - Erythromelalgia in a patient with AIDS.
AB  - Erythromelalgia is a clinical syndrome characterized by burning pain in the
      extremities together with erythema and increased skin temperature. Typically, the
      patients experience relief from cold, and aggravation from warmth. Symptoms are
      hypothesized to be caused by arteriovenous shunting and reduced nutritive skin
      capillary perfusion with corresponding tissue hypoxia. Erythromelalgia is most
      often primary, but may be secondary to a wide variety of diseases. We report
      erythromelalgia in a patient with acquired immune deficiency syndrome (AIDS). At
      peak pain intensity he actively cooled hands and feet for more than 12 h/day.
      Many doctors handling human immunodeficiency virus/AIDS patients are unfamiliar
      with erythromelalgia, and the condition can easily be overlooked, especially the
      more common milder cases.

PMID- 11444275
TI  - Photosensitivity induced by oral itraconazole.
AB  - A case of photosensitivity induced by itraconazole is reported. A 70-year-old
      woman had erythema, oedema and vesicles on sun-exposed areas after 5 days of
      itraconazole treatment for oral candidiasis. Oral photochallenge using
      itraconazole and sun irradiation was positive, but photopatch test was negative.
      Photosensitivity from azoles is an uncommon adverse effect. Only three other
      cases have been described, two induced by ketoconazole and one by itraconazole.

PMID- 11444276
TI  - Occupational protein contact dermatitis and paronychia from natural rubber latex.
AB  - Protein contact dermatitis (PCD) is a chronic recurrent dermatitis caused by
      contact with a proteinaceous material. PCD may also present as paronychia. Here a
      case of PCD and paronychia from natural rubber latex (NRL) is presented. The
      correct diagnosis would not have been established if prick testing with NRL had
      not been performed. This case shows that contact allergy presenting as dermatitis
      may occur despite negative patch test results. PCD from NRL may be relatively
      common, although very few cases have been published. This is probably due to the
      fact that the term contact urticaria is so closely connected to NRL that
      automatically all cases of type I allergy to NRL are considered contact
      urticaria, although the clinical picture is a dermatitis, i.e. PCD.

PMID- 11444277
TI  - Burn-induced linear IgA dermatosis.
AB  - There have been several reports of linear IgA dermatosis (LAD) associated with
      drug exposure and lymphoproliferative malignancy, but trauma and burns have been
      suggested only in patients with bullous pemphigoid. We present a case of burn
      induced LAD in a 48-year-old caucasian male presenting with a recent history of
      blistering eruption on the periphery of a cicatricial area caused by boiling
      methyl alcohol. Clinically, he presented a widespread bullous eruption. The
      direct immunofluorescence examination of a perilesional biopsy revealed an
      intense homogeneous linear pattern of IgA deposition consistent with the
      diagnosis of LAD. The patient responded to therapy with systemic steroids.

PMID- 11444278
TI  - Polypoid clear cell acanthoma: case report.
AB  - Clear cell acanthoma of Degos is a rare benign tumour of epidermal origin with
      distinct histological features. Clinically, clear cell acanthoma is characterized
      by a 'stuck on' appearance of a nodule or dome-shaped plaque that usually occurs
      on the legs of middle-aged or elderly persons. We observed an unusual case of
      polypoid clear cell acanthoma on the right thigh of a 58-year-old male.

PMID- 11444279
TI  - Microalbuminuria as a subclinical marker of renal impairment in subjects with
      psoriasis vulgaris.

PMID- 11444280
TI  - Pityriasis rubra pilaris: a retrospective study of 12 patients.

PMID- 11444281
TI  - The significance of karyorrhexis in lichen planus.

PMID- 11444282
TI  - Immunohistochemical findings in granuloma faciale. The role of eosinophilic
      granulocytes.

PMID- 11444283
TI  - Drug eruptions: a study including all inpatients and outpatients at a dermatology
      clinic of a university hospital.

PMID- 11444284
TI  - Childhood atopic dermatitis treated with specific food elimination.

PMID- 11444285
TI  - Perioral psoriasis.

PMID- 11444286
TI  - Society for the Study of Reproduction. 34th annual meeting. July 28 - August 1,
      2001. Ottawa, Ontario, Canada. Abstracts.

PMID- 11444287
TI  - Stem cell research needs united support.

PMID- 11444288
TI  - A global paleoclimate observing system.

PMID- 11444290
TI  - Earth system science sentiments.

PMID- 11444289
TI  - Climate variability and global warming.

PMID- 11444292
TI  - Impact of hairy vetch cover crop on herbicide transport under field and
      laboratory conditions.
AB  - This study was conducted to evaluate the effect of hairy vetch cover crop residue
      on runoff losses of atrazine and metolachlor under both no-till corn field plots
      and from a laboratory runoff system. A 2-year field study was conducted in which
      losses of atrazine and metolachlor from vetch and non-vetch field plots were
      determined from the first runoff event after application (5 and 25 days after
      application in 1997 and 1998, respectively). A laboratory study was conducted
      using soil chambers, designed to simulate field soil, water, vegetation, and
      herbicide treatment conditions, subjected to simulated rain events of 5, 6, 20
      and 21 days after application, similar to the rainfall pattern observed in the
      field study. Atrazine losses ranged from 1.2 to 7.2% and 0.01 to 0.08% and
      metolachlor losses ranged from 0.7 to 3.1% and 0.01 to 0.1% of the amount applied
      for the 1997 and 1998 runoff events, respectively. In the laboratory study,
      atrazine runoff losses ranged from 6.7 to 22.7% and 4.2 to 8.5% and metolachlor
      losses ranged from 3.6 to 9.8% and 1.1 to 4.7% of the amount applied for the 5-6
      and 20-21 day events, respectively. The lower losses from the field study were
      due to smaller rainfall amounts and a series of small rains prior to the runoff
      event that likely washed herbicides off crop residue and into soil where
      adsorption could occur. Runoff losses of both herbicides were slightly higher
      from non-vetch than vetch field plots. Losses from the laboratory study were
      related to runoff volume rather than vegetation type.

PMID- 11444293
TI  - Photolysis of PAHs in aqueous phase by UV irradiation.
AB  - The photooxidation of polycyclic aromatic hydrocarbons (PAHs) was investigated in
      an aqueous ethanolic solution irradiated with a medium-pressure mercury lamp in
      laboratory photoreactors equipped with a quartz immersion well. Degradation
      photolysis of fluorene was more efficient than sensitized photolytic oxidation in
      the presence of TiO2 suspensions. Photolysis kinetics was dependent on molecular
      weight and the presence and type of substituents. During the photolytic
      degradation of fluorene and its derivatives, 9-fluorenone and its corresponding
      derivatives, which were more resistant to photolysis, were formed.

PMID- 11444294
TI  - Polycyclic aromatic hydrocarbons: a QSPR study. Quantitative structure-property
      relationships.
AB  - This work deals with 48 substances composed exclusively of unsubstituted six
      membered fused aromatic rings. In the first step, physicochemical properties
      which are relevant in environmental studies such as the boiling temperature (Tb),
      the retention index (RI), n-octanol/water partition coefficient (KOW) and
      solubility (S) are related with a series of electronic, geometric and topological
      descriptors. Among them are: electron affinity, the difference between electron
      affinity and ionization potential (GAP), Wiener, and connectivity indexes,
      volume, surface area, length-to-breadth ratio and enthalpy of formation. In a
      second step, these properties were incorporated into the descriptor matrix to
      build several quantitative structure-property relationships and to obtain
      prediction rules for the log KOC, log KOA, bioconcentration factor (BCF) and
      Henry's law constant (H). Finally, the photo-induced toxicity of freshwater
      organism Daphinia-Magna is modeled using the following transformed electronic
      descriptors: electron affinity, ionization potential and Gap.

PMID- 11444295
TI  - Polycyclic aromatic hydrocarbons (PaHs) in subcutaneous biopsies of Mediterranean
      cetaceans.
AB  - The aim of the present study was to measure polycyclic aromatic hydrocarbon (PAH)
      levels in free-ranging Mediterranean cetaceans as they are likely to cause
      chemical stress in the organisms of this basin. Blubber samples were collected
      from live specimens of fin whales (Balaenoptera physalus) and striped dolphins
      (Stenella coeruleoalba) by means of biopsies, a non-destructive biological
      method. Fin whales were sampled in the Ligurian Sea, whereas striped dolphins
      were collected in the Ligurian and the Ionian Seas. A fingerprint of 14 PAHs was
      obtained for both species. In whales, the median value of total PAHs was 1970 ppb
      fresh weight (f.w.) while median carcinogenic PAH values were 89.80 ppb f.w.; in
      dolphins, the median values of total and carcinogenic PAHs were 29,500 and 676.00
      ppb f.w., respectively. The different PAH values between the two species can be
      attributed to the different positions they take in the Mediterranean food web.
      The sampling period significantly influenced PAH concentrations of fin whales.

PMID- 11444296
TI  - PAHs associated with the leaves of three deciduous tree species. II: uptake
      during a growing season.
AB  - Leaves from three species of deciduous tree (oak, ash and hazel) were sampled at
      intervals through a growing season in a mature, mixed-deciduous woodland.
      Polycyclic aromatic hydrocarbon (PAH) concentrations remained within a small
      range for all species between May and September, deviating significantly only
      when increases in atmospheric concentrations of PAHs (notably from the 'Bonfire
      night' festival in early autumn) have been shown. We concluded that the influence
      of air concentrations was more important than meteorological conditions
      (temperature, humidity and rainfall) in determining plant concentrations of PAHs
      over a growing season. Concentrations of 4-, 5- and 6-ring PAHs were positively
      correlated with time for all species, but there were significant differences in
      the PAH profile between species sampled from the canopy (oak and ash) compared
      with the understorey (hazel). Oak and ash had similar PAH profiles, while hazel
      leaves had proportionally greater concentrations of the heavier molecular weight
      (4-, 5- and 6-ring) PAHs, and the ratios of these compounds to 3-ring PAHs was
      positively correlated with time. This affirms earlier work conducted on the same
      species in the same woodland, where we concluded that the canopy was filtering
      particles and attendant PAHs from air passing over or through it, and that these
      particles were transferred to the understorey and the woodland floor.

PMID- 11444297
TI  - No enhancement in bioconcentration of organic contaminants by low levels of DOM.
AB  - The aim of the present work was to systematically study the effect of low
      concentrations of dissolved organic matter (DOM) on the bioconcentration of
      organic contaminants, in order to show whether the phenomenon of enhanced
      bioconcentration factors (BCFs), that has been reported in the literature, is
      generally found at low levels of DOM or if BCF enhancements are more likely due
      to a random scatter in the experimental data. The first part of the study tested
      the hypothesis that low levels of DOM affect the uptake kinetics of organic
      contaminants, leading to transient enhancements of BCFs, relative to DOM-free
      controls, which could have been reported as BCF enhancements in short-term
      studies. We found that the presence of low concentrations of two different types
      of DOM consistently decreased the bioconcentration of benzo[a]pyrene (BaP) in the
      water flea Daphnia magna at all exposure times (1-24 h), and that no transient
      BCF enhancements occurred. The second part of the study systematically
      investigated if low concentrations of DOM from a wide range of different aquatic
      systems can cause enhancements in the bioconcentration of organic contaminants.
      Water fleas were exposed to combinations of four different organic contaminants
      (BaP, tetrachlorobiphenyl, pentachlorophenol and naphthalene) with low
      concentrations of 12 different types of DOM that had been collected from various
      regions throughout Europe. In several of the DOM treatments, we found mean BCFs
      being higher than mean BCFs in the controls (especially for naphthalene). This
      shows that the experimental setup used in this study (and similarly in previous
      studies) can produce seeming BCF enhancements at low concentrations of DOM.
      However, statistical analyses showed that treatment means were not significantly
      different from control means. Thus, this systematic study suggests that the BCF
      enhancements that have been reported in the literature are more likely the result
      of random, experimental variations than the result of a systematic enhancement of
      bioconcentration.

PMID- 11444298
TI  - Treatment of N,N-dimethylacetamide waste gas by a trickle-bed air biofilter.
AB  - The system performance of a trickle-bed air biofilter (TBAB) for treating N,N
      dimethylacetamide (DMAC) waste gas was investigated under different gas flow
      rates and influent concentrations. In the pseudo-steady-state conditions, the
      DMAC elimination capacity increased but the removal efficiency decreased as the
      influent loading increased. More than 90% and 80% DMAC removal efficiencies are
      achieved for influent loadings below 20.2 and 34.5 g DMAC/m3/h, respectively. The
      TBAB appears to be an effective treatment process for controlling DMAC emission
      with low-to-medium loadings and the effectiveness could be maintained over a long
      period operation.

PMID- 11444299
TI  - Extraction of organic contaminants from marine sediments and tissues using
      microwave energy.
AB  - In this study, we compared microwave solvent extraction (MSE) to conventional
      methods for extracting organic contaminants from marine sediments and tissues
      with high and varying moisture content. The organic contaminants measured were
      polychlorinated biphenyl (PCB) congeners, chlorinated pesticides, and polycyclic
      aromatic hydrocarbons (PAHs). Initial experiments were conducted on dry standard
      reference materials (SRMs) and field collected marine sediments. Moisture content
      in samples greatly influenced the recovery of the analytes of interest. When wet
      sediments were included in a sample batch, low recoveries were often encountered
      in other samples in the batch, including the dry SRM. Experiments were conducted
      to test the effect of standardizing the moisture content in all samples in a
      batch prior to extraction. SRM1941a (marine sediment). SRM1974a (mussel tissue),
      as well as QA96SED6 (marine sediment), and QA96TIS7 (marine tissue), both from
      1996 NIST Intercalibration Exercise were extracted using microwave and
      conventional methods. Moisture levels were adjusted in SRMs to match those of
      marine sediment and tissue samples before microwave extraction. The results
      demonstrated that it is crucial to standardize the moisture content in all
      samples, including dry reference material to ensure good recovery of organic
      contaminants. MSE yielded equivalent or superior recoveries compared to
      conventional methods for the majority of the compounds evaluated. The advantages
      of MSE over conventional methods are reduced solvent usage, higher sample
      throughput and the elimination of halogenated solvent usage.

PMID- 11444300
TI  - Organochlorine burdens in blood of ringed and bearded seals from north-western
      Svalbard.
AB  - Ringed seal (Phoca hispida) and bearded seal (Erignathus barbatus) are the main
      prey of polar bears (Ursus maritimus), and information on organochlorines (OCs)
      in these pinniped species is important to understand the transport, fate and
      effects of persistent organic pollutants in the Arctic ecosystem. Thus, OCs were
      analysed in blood samples of bearded and ringed seals from the coastal ecosystem
      of the north-western Svalbard archipelago (Kongsfjorden, 78.55degrees N). The
      relative contribution of OCs could be ranked as follows: Ringed seal females:
      sigmaPCB > sigma DDT > sigma CHL > sigma HCH > HCB > Mirex. Ringed seal males:
      sigma PCB > or = sigma DDT > sigma CHL > sigma HCH > or = HCB > Mirex. Bearded
      seal females: sigma PCB > sigma HCH > or = sigma CHL > sigma DDT > Mirex > HCB.
      Bearded seal males: sigma PCB > sigma DDT > or = sigma CHL > sigma HCH > Mirex >
      or = HCB. The concentrations of sigmaPCB and sigma DDT were higher in ringed
      seals than in bearded seals, whereas sigma HCH was higher in bearded than in
      ringed seals. In ringed seal females and males sigma PCB was 337 +/- 95 ng/g (n=
      6) and 625 +/- 443 ng/g (n=6), whereas sigma DDT was 165 +/- 47 ng/g (n=6) and
      621 +/- 559 ng/g (n = 6), respectively. In bearded seal females and males,
      sigmaPCB was 159 +/- 132 ng/g (n = 6) and 248 +/- 93 ng/g (n = 5), whereas
      sigmaDDT was 46 +/- 41 ng/g (n = 6) and 161 +/- 71 ng/g (n = 5), respectively.
      The inter-species differences are caused by a higher trophic position of ringed
      seals in the Svalbard ecosystem compared to bearded seals. OC levels in ringed
      seals at Svalbard are similar to those reported from the North-American Arctic
      and in the lower range compared to previously reported data from Svalbard.

PMID- 11444301
TI  - Photoinductive properties of soil humic acids and their fractions obtained by
      tandem size exclusion chromatography-polyacrylamide gel electrophoresis.
AB  - Humic acids (HAs) from three soils of different origin (Chernozem, Ferralsol and
      Ranker) have been fractionated by coupling size exclusion chromatography (SEC)
      and polyacrylamide gel electrophoresis (PAGE) on three fractions (fractions A, B,
      C + D) with different molecular sizes (MSs) and exactly defined electrophoretic
      mobility (EM). Fractions identically marked had similar EM and MS, independently
      of HA sources. The photoinductive properties of the whole HAs and their fractions
      were compared by studying the photoinduced transformation of fenuron at 365 nm.
      High MS fractions A and B appeared to exhibit poor photoinductive activities
      compared to the whole HAs, whereas low MS fraction C + D in Chernozem and Ranker
      were more efficient than the whole HAs. A fourth intermediary fraction containing
      a mixture of fractions B and C + D with small amount of D was shown to
      photoinduce poorly the transformation of fenuron. It was therefore concluded that
      the molecules capable of photoinducing the transformation of fenuron were mainly
      contained in fraction D. Fluorescence properties of Chernozem HA and its
      fractions have been tested. Fraction C + D exhibited a very similar fluorescence
      emission spectrum in comparison with the whole HA and in contrast, the fractions
      A and B emitted very weakly.

PMID- 11444302
TI  - The modelling of trichloroethene photodegradation in Brij 35 surfactant by two
      stage reaction.
AB  - Various clean-up technologies have been developed for the removal and/or
      destruction of trichloroethene (TCE) in the subsurface. Surfactant-aided soil
      washing followed by photodegradation could be a promising approach to such a
      task. The modelling of TCE photodegradation by UV in Brij 35 surfactant micelles
      is therefore investigated. Two stages of TCE degradation are observed in
      surfactant Brij 35 systems. A lag phase is observed at the commencement of the
      degradation, but the duration of the lag phase is significantly reduced as the
      initial pH increases. As the overall decay of TCE is also found to be faster at
      higher pH levels, it is suggested that the free radical reaction is dominant at
      high pH levels, and the formation of lag phases is mainly due to the deficiency
      of free radicals at lower pH levels. Since the period of the lag phase gradually
      decreases with the increase of initial pH level, and the two pseudo first-order
      reaction constants (one for the lag phase and one for the subsequent fast decay)
      for TCE decay in both stages are also pH dependent, a non-steady-state
      mathematical model is developed for the prediction of TCE photodegradation in
      Brij 35 solutions, in which the remaining fraction of TCE (C/C0) in the system
      can be determined at any instant by using a simple parameter of the initial
      system pH.

PMID- 11444303
TI  - Investigation of uptake, translocation and fate of trichloroacetic acid in Norway
      spruce (Picea abies/L./Karst.) using 14C-labelling.
AB  - [1,2-14C]TCA of a high specific activity (3.7 GBq/mmol) and appropriate
      radioindicator techniques were used, to study the effect of trichloroacetic acid
      (TCA) on conifers. Easy uptake of TCA from soil through spruce roots and its
      further translocation by the transpiration stream up to the needles (where damage
      of the photosynthetic apparatus occurs) has been proved. During the growth
      period, after one-shot load of TCA, the uptake was most intensive in current-year
      needles at first; over an extended period a decrease in the level of [1,2-14C]TCA
      derived radioactivity was found in the current-year needles while in older
      needles (C + 2), the level rose. Symptoms of TCA biodegradation and/or metabolism
      were found in the plant/soil system under study. During an eight-week exposure
      significant losses of radioactivity into the atmosphere were noticed, at least a
      part of them in the form of carbondioxide. The results of these more or less
      preliminary experiments demonstrated the suitability and advantages of the
      radioisotopic technique used.

PMID- 11444304
TI  - Analysis of photochemical pollution in summer and winter using a photochemical
      box model in the center of Tokyo, Japan.
AB  - In order to give an effective and rapid analysis of the photochemical pollution
      and information for emission control strategies, a photochemical box model (PBM)
      was applied to one moderate summer episode, 11 July 1996, and one typical winter
      episode, 3 December 1996, in the center of Tokyo, Japan. The box model gave a
      good prediction of the photochemical pollution with minimal investment. As
      expected, the peak ozone in summer is higher than in winter. The NOx
      concentrations in winter are higher than those in summer. In summer, NO and NO2
      have one peak in the morning. In winter, NO and NO2 show two peaks during the
      day. Three model runs including no reactions, a zero ozone boundary condition and
      dark reactions were conducted to understand the photochemical processes. The
      effects of emission reduction on the formation of the photochemical pollution in
      the center of Tokyo have been studied. The results show that the reduction of
      NMHC emission can decrease the ozone, however, the reduction of NOx emission can
      increase the ozone. It can be concluded that if the NOx emission are reduced, the
      reduction of NMHC should be more emphasized in order to decrease the ozone
      concentration in the center of Tokyo, Japan, especially the reduction of the NMHC
      from stationary source emission.

PMID- 11444305
TI  - Degradation of herbicides in two sandy aquifers under different redox conditions.
AB  - We examined the potential for complete degradation (mineralisation) of the four
      [ring-U-14C]herbicides mecoprop, isoproturon, atrazine, and metsulphuron-methyl
      in two sandy aquifers representing aerobic, denitrifying, sulphate-reducing, and
      methanogenic conditions. Slurries with sediment and groundwater were set-up
      aerobically or anaerobically in the presence of the electron-acceptor prevailing
      at the sampling site, amended with 25 microg l(-1) herbicide, and incubated at 10
      degrees C. Considerable mineralisation was only observed in sediment from the
      plough layer incubated aerobically. Here, 30% of 14C-mecoprop was recovered as
      14CO2 after 15 days and 15% of isoproturon was recovered as 14CO2 after 267 days.
      Only 7% of mecoprop was recovered as 14CO2 after 313 days in sediment from the
      aquifer below sampled at 1.95-3.00 mbs (m below the surface). In denitrifying and
      methanogenic slurries, 3% of 14C added as mecoprop was recovered as 14CO2.
      Isoproturon was not mineralised except in the aerobic plough layer, and atrazine
      and metsulphuron-methyl were not mineralised under any of the conditions applied.

PMID- 11444306
TI  - Formation of nitrophenols upon UV irradiation of phenol and nitrate in aqueous
      solutions and in TiO2 aqueous suspensions.
AB  - The formation of nitrophenols was studied as a consequence of ultra violet (UV)
      irradiation of aqueous solutions of phenol and nitrate in the range of pH 1-12.
      The study was performed both in homogeneous phase and in the presence of water
      suspended TiO2. The effects of pH, dissolved oxygen and 2-propanol as .OH
      scavenger have been evaluated. A reaction mechanism is proposed, based on the
      experimental results.

PMID- 11444307
TI  - Continuous monitoring of photocatalytic treatments by flow injection. Degradation
      of dicamba in aqueous TiO2 dispersions.
AB  - The possible use of flow injection (FI) to monitor the photocatalytic
      mineralization of dicamba (3,6-dichloro-2-methoxybenzoic acid) present at the
      trace level in aqueous solutions containing TiO2 suspensions has been evaluated.
      Experiments were performed in a stirred photochemical reactor equipped with a
      simple FI manifold, integrating an online filtration unit able to perform the
      monitoring of the UV absorbance of the irradiated solution every 4 min. The light
      source used was a medium pressure mercury lamp (125 W). During the initial steps
      of the reaction the formation of UV absorbing intermediates, which completely
      disappear in less than 80 min, was evidenced. Additional HPLC, DOC and chloride
      ion measurements carried out on manually taken samples confirmed the complete
      mineralization of dicamba within about 90 min. The proposed on-line monitoring
      looks particularly suitable for the control of degradation treatments where
      primary degradation and mineralization steps take place after a comparable
      irradiation time.

PMID- 11444308
TI  - Aerosolization of an anionic surfactant (LAS) and dissolved organic carbon (DOC)
      under laboratory conditions.
AB  - Aerosolization of natural salt and brackish waters under laboratory conditions is
      responsible for the transfer of synthetic surfactants such as linear alkylbenzene
      sulphonate (LAS) from water to the atmosphere. Excluded the lagoon sample which
      stands apart, on the average ca. 45% of the LAS present at concentrations between
      0.1 and 4.1 microg l(-1) in the tested coastal and offshore marine and lagoon
      waters was transferred to the aerosol extract. The distribution of the individual
      LAS homologs in the aerosol is very similar to that in water, which indicates no
      preferential removal from the bulk water of any LAS homolog. The fraction of
      dissolved organic carbon (DOC) undergoing aerosolization under the same
      conditions for each tested sample was on an average ca. 3.3%, corresponding to
      ca. 5.6 mg l(-1). On the average, the enrichment factor of the sea samples,
      resulting from the changing of the LAS/DOC ratio before and after aerosolization,
      was ca. 20.

PMID- 11444309
TI  - Use of zebra mussel (Dreissena polymorpha) to assess trace metal contamination in
      the largest Italian subalpine lakes.
AB  - Trace metal (Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn) contamination was evaluated in
      zebra mussels from the lakes Maggiore, Lugano, Como, Iseo and Garda, which are
      located in the most highly populated and industrialised area in Italy. Zebra
      mussels from Lake Maggiore contained the highest concentrations (3.44, 1.51,
      4.97, 0.158, 5.87, 346 microg g(-1) for Cd, Co, Cr, Hg, Pb, Zn, respectively) of
      all metals analysed except Cu and Ni. The lowest levels of most metals were in
      animals from Garda and Lugano (0.78 and 0.60 microg g(-1) for Cd, 2.87 and 2.03
      microg g(-1) for Cr, 0.065 and 0.049 microg g(-1) for Hg, 12.1 and 11.9 microg g(
      1) for Ni, 1.96 and 2.46 microg g(-1) for Pb, 158 and 163 microg g(-1) for Zn).
      The most contaminated sites and possible local sources of metals were identified
      for each lake, and the lakes classified into quality classes concerning metal
      pollution.

PMID- 11444310
TI  - Concentrations of monosaccharides in humic substances in the early stages of
      humification.
AB  - Deteriorated liquid packaging board (LPB) and biowaste compost are matrices,
      mainly consisting of cellulose, in the early stages of humification. Degradative
      studies on these matrices allow an examination of the role of carbohydrates in
      the synthesis of humic substances. Samples of different age were collected and
      divided by extraction into hot water extract (HWE), bitumen, humic acid (HA),
      fulvic acid (FA) and humin or residual fibre fractions. The following
      monosaccharides were identified in these fractions: L-arabinose, D-ribose, D
      xylose, L-fucose, D-mannose, D-fructose, D-galactose, D-glucose, L-rhamnose and
      xylitol. The main component in all fractions was glucose. The concentrations of
      monosaccharides in humic acids (HAs) of LPB ranged from 67 to 503 mg/g of organic
      matter, and the concentrations in HAs of compost from 52 to 101 mg/g. As a
      general trend, the concentrations of monosaccharides decreased during LPB
      degradation and composting in all fractions. At the same time the relative
      amounts of D-xylose, D-mannose and D-galactose increased in HAs of compost
      samples.

PMID- 11444311
TI  - Combined treatment of textile effluent using the sequence Phanerochaete
      chrysosporium-ozone.
AB  - Textile effluents cause a high environmental impact when released into the
      environment without correct treatment. In this work, we have evaluated the
      capacity of treatment of a textile effluent using a biological and a chemical
      method using the sequence Phanerochaete chrysosporium-ozone. The fungal treatment
      was performed by direct incubation of a fungus spore suspension in textile
      effluent for nine days. Then, the effluent was ozonized at pH 11 and room
      temperature. Color, total organic carbon, molecular mass distribution and total
      phenols were determined. In biological experiments, enzymatic activity (lignin
      peroxidase, manganese peroxidase and laccase) were also monitored. Toxicity tests
      were carried out with Scenedesmus subspicatus and with Escherichia coli. Good
      decoloration, total phenols reduction and textile effluent molecular mass
      reduction were obtained during the process. No significant total organic carbon
      reduction was observed. The toxicity of the textile effluent was reduced with
      both test organisms showing no inhibition at the end of the treatment.

PMID- 11444312
TI  - Biodegradation of aliphatic-aromatic copolyesters: evaluation of the final
      biodegradability and ecotoxicological impact of degradation intermediates.
AB  - The biological degradation behaviour of the aliphatic-aromatic copolyester
      Ecoflex was investigated with regard to the degree of degradation and the
      intermediates formed during the degradation process. The individual thermophilic
      strain Thermomonospora fusca, isolated from compost material, was used for the
      degradation experiments in a defined synthetic medium at 55 degrees C. After 22
      days of degradation more than 99.9% of the polymer had depolymerized and with
      regard to the degradation of the diacid and diol components of Ecoflex only the
      monomers of the copolyesters (1,4-butanediol, terephthalate and adipate) could be
      detected by gas chromatography/mass spectroscopy (GC-MS) measurements in the
      medium. In interrupted degradation experiments predominantly the monoesters of
      adipic acid and terephthalic acid with 1,4-butanediol were observed in addition
      to the monomers. In toxicological tests with Daphnia magna and Photobacterium
      phosphoreum no significant toxicological effect was observed, neither for the
      monomeric intermediates nor for the oligomeric intermediates. From a risk
      assessment it can be concluded that there is no indication for an environmental
      risk when aliphatic-aromatic copolyesters of the Ecoflex-type are introduced into
      composting processes.

PMID- 11444313
TI  - Monitoring of organochlorine pesticide residues in the Indian marine environment.
AB  - Organochlorine pesticide residues in sediment and fish samples collected from the
      east and west coasts of India are presented. HCH isomers and DDT and its
      metabolites are the predominantly identified compounds in most of the samples.
      Despite the higher quantity of consumption, HCH and DDT levels in fish in India
      were lower than those in temperate countries suggesting a lower accumulation in
      tropical fish, which could be due to rapid volatilization and degradation of
      these insecticides in the tropical environment. The predominance of alpha- and
      beta-HCH reflect the use of technical grade HCH in India. The high temperature in
      the tropics also enhances the elimination rate of chemicals in fish, as the
      biological half-lives of semivolatile compounds such as DDT are short at high
      temperature.

PMID- 11444314
TI  - Spray deposits of crop protection products on plants--the potential exposure of
      non-target arthropods.
AB  - Spray deposits of plant protection products on cultivated plants present a
      potential hazard to non-target arthropods. This hazard is considered in the risk
      assessment procedure when such products are registered. The results of deposit
      measurements in the laboratory and field, including mean spray deposits on plant
      surfaces, their variability and their relation to the delivered dose are
      presented. Initial deposits expressed as ng/cm2 plant surface were measured on
      individual leaves of various plant species using a fluorescent tracer. The
      results show that the mean deposit is plant-specific but with a high degree of
      variability. Mean deposits on field-grown cereals were 3, 9 (growth stage BBCH
      10) and 4, 7-14 ng/cm2 (growth stage BBCH 29-63) at a delivered dose rate of 20 g
      sodium flourescein (SF) per ha. This is equivalent to 200 ng tracer per cm2
      ground area. On apple leaves, mean deposits varied between 18 and 50 ng/cm2 at a
      rate of 20 g tracer/10,000 m2 fruitwall. Coefficients of variation of leaf
      deposits ranged between 30% and 90%. In addition to the leaf-to-leaf variability,
      there was a notable variation of the deposit on individual leaves themselves as
      shown for wheat. Data from field measurements were supported principally by data
      from tray-grown plants on a laboratory spray track which gives information on
      targets positioned in a more or less two-dimensional system.

PMID- 11444315
TI  - Polychlorinated biphenyls and hexachlorobenzene in atmosphere, sea-surface
      microlayer, and water measured with semi-permeable membrane devices (SPMDs).
AB  - The time evolution of polychlorinated biphenyl (PCB) levels and hexachlorobenzene
      (HCB) levels in air, seawater, and at the sea-air boundary layer was examined
      during autumn and winter at a near-shore location in the Western Wadden Sea
      (Netherlands), using semi-permeable membrane devices (SPMDs). Performance
      reference compounds (PRCs) were added to the SPMDs prior to exposure for
      measuring the in situ exchange kinetics. For PCBs, a fair degree of equilibrium
      between atmosphere and water was found. HCB concentrations in the atmosphere were
      about eight times higher than the equilibrium concentration. PCB concentrations
      in seawater and atmosphere fell by a factor of 2-10, respectively, during the
      sampling period. HCB concentrations in water increased by a factor of 2.
      Atmospheric concentrations of HCB showed a decrease by a factor of about 10.
      Results for the sea-surface microlayer (SSM) deployment showed that the chemical
      activities at the air-water interface did not differ from those in deeper water
      layers. This means that the SSM was of no special toxicological significance in
      this study as far as PCBs and HCB are concerned.

PMID- 11444316
TI  - A screening model-based study of transport fluxes and fate of airborne mercury
      deposited onto catchment areas.
AB  - Dynamics of airborne mercury deposited onto catchment areas is investigated
      within the framework of a simulation model. Model results show that, for a
      particular atmospheric deposition rate, significant interannual variability in
      mercury transport flux in catchments is caused by climatology and corresponding
      differences in catchment soil loss rates; in comparison to the normal year,
      runoff flux increased by a factor of 2-3 for the wet year (rainfall 35% above
      normal) while for the dry year (rainfall 18% below normal) runoff flux decreased
      by factors of 5-7. The interaction of parameters describing soil type, topography
      and vegetation cover causes variability in both transport and emission fluxes
      among catchments; as soil loss rate increases by a factor of 5 due to variations
      in these parameters among the examined catchments, annual average transport flux
      increases by a factor of 3; and annual average emission flux of mercury (as Hg0)
      from soil to the atmosphere decreases by a factor of 2 due to the decreased
      levels of soil mercury associated with catchment soil loss increases. Seasonal
      variability of transport flux is associated with seasonal changes in
      precipitation and soil loss rates while seasonal changes of emission flux are
      primarily due to changes in soil moisture regime and temperature. Although
      modeled results are consistent with observational data from previous studies,
      they must be interpreted in a relative sense due to the screening-level character
      of this study.

PMID- 11444317
TI  - Does tumor size influence the outcome of laparoscopic adrenalectomy?
AB  - BACKGROUND: Laparoscopic adrenalectomy is safe and effective for small adrenal
      tumors, but its role for large adrenal tumors and the influence of tumor size on
      the outcome of laparoscopic adrenalectomy have been questioned. PATIENTS AND
      METHODS: Thirty-one patients with unilateral adrenal tumors operated on between
      January 1997 and April 2000 were selected for this study. The indications for
      surgery were Conn's adenoma in 16 patients, pheochromocytoma in 7 patients,
      Cushing's adenoma in 4 patients, and incidental lesions in 4 patients. The
      patients were divided in two groups: 19 patients with tumors <3.5 cm (Group I)
      and 12 patients with tumors > or = 3.5 cm (Group II). The outcomes of the two
      groups were compared. RESULTS: None of the laparoscopic procedures was converted
      to open surgery. The tumor size correlated with operative time (r = 0.434; P =
      0.015) and blood loss (r = 0.513; P = 0.003), with both being significantly
      greater for larger tumors. No patient required a blood transfusion during or
      after surgery. One preoperative complication occurred in Group I. There was no
      peroperative complication in Group II. The median postoperative hospital stay and
      opioid requirement did not differ significantly between the groups. One patient
      in Group I developed pneumonia, while no postoperative complications were
      recorded in Group II. CONCLUSION: Surgery for large adrenal tumors can safely be
      performed laparoscopically with outcomes comparable to those of surgery for small
      tumors.

PMID- 11444318
TI  - Simple technique for proper approximation and closure of peritoneal and rectus
      sheath defects at port site after laparoscopic surgery.
AB  - Complex intra-abdominal surgical procedures can now be performed with
      laparoscopy, and laparoscopic cholecystectomy has become the gold standard in the
      care of patients with cholelithiasis. This and other surgically challenging
      procedures involve use of multiple large (10-mm-15-mm) ports. A standard
      laparoscopic cholecystectomy employs two 10-mm trocar incisions. Development of
      incisional hernia from these port sites is well recognized unless the rectus
      sheath is closed properly. This makes proper closure of the incisions for larger
      ports critical, especially 10-mm to 15-mm ports. However, securing abdominal wall
      bleeding and closing facial defects through a small incision can be a cumbersome
      task. We have developed a simple technique using the regular curved needle and
      sutures for closure of rectus sheath defects through a small port-site incision.

PMID- 11444319
TI  - New ergonomic design criteria for handles of laparoscopic dissection forceps.
AB  - BACKGROUND: The shape of laparoscopic instrument handles can cause physical
      discomfort. This problem may be ascribed to a lack of standards for instrument
      design. In this study, new ergonomic requirements for the design of laparoscopic
      dissection forceps were created. Three representative handles (a Karl Storz
      [click-line] scissors handle, an Access Plus scissors handle, and an Aesculap
      cylindrical handle) currently available on the market were evaluated according to
      the new list of ergonomic criteria. MATERIALS AND METHODS: The handles were
      subjectively (questionnaire) and objectively (video analyses) tested in order to
      find out whether the new requirements are valid for the evaluation and design of
      instrument handles. RESULTS: The outcome of the subjective and objective tests
      matched the predictions by the new criteria list. New criteria were introduced
      (neutral wrist excursions), and existing general criteria were specified (e.g., a
      minimal contact area of 10 mm). Significant differences were found among the
      three handles. The Storz handle met 8 of the 10 requirements, the Access handle
      met 5, and the Aesculap handle met only 4. CONCLUSIONS: The new list of ergonomic
      requirements is a valid tool to determine the ergonomic value of a handle for
      laparoscopic dissecting tasks. It gains its strength from its specialized
      character. Significant differences were found among the three tested handles.
      Cylindrical handles were inferior to scissors handles.

PMID- 11444320
TI  - Robotic Nissen fundoplication: alternative surgical technique for the treatment
      of gastroesophageal reflux disease.
AB  - The first robotic Nissen fundoplication using the da Vinci robotic surgical
      system was performed on a 56-year-old woman with a 20-year history of severe
      gastroesophageal reflux disease refractory to medical management. The recovery
      was uneventful, and follow-up continues.

PMID- 11444321
TI  - A giant ectopic ovary.
AB  - A young woman with a congenital chest-wall defect presented with abdominal pain,
      irregular menses, and a palpable mass at the defect. The mass, removed
      laparoscopically, was found to be a functioning ovary that tracked along the
      retroperitoneum, reflecting its embryologic origin.

PMID- 11444322
TI  - Laparoscopic cholecystectomy in the presence of a lumboperitoneal shunt.
AB  - Laparoscopic cholecystectomy was performed safely in a 70-year-old man with a
      lumboperitoneal shunt. Techniques for preventing retrograde flow of carbon
      dioxide are described.

PMID- 11444323
TI  - Symptomatic post-traumatic cyst of the liver: treatment by laparoscopic surgery.
AB  - We report a case of a large post-traumatic liver cyst in a symptomatic patient
      treated by laparoscopic excision in an ambulatory setting. This rare lesion can
      be treated safely by this alternative modality on an outpatient basis, with
      minimal morbidity.

PMID- 11444324
TI  - Tracheal injury during endoscopic hemithyroidectomy.
AB  - Unsuspected tracheal injury during endoscopic hemithyroidectomy is described. The
      diagnosis was delayed because of absent symptomatology. Surgical repair was
      planned but deferred because of infection. The patient was managed with a
      tracheostomy tube and antibiotics, and the wound healed completely without any
      residual abnormality or complications.

PMID- 11444325
TI  - Abdominal wall abscess secondary to spilled gallstones: late complication of
      laparoscopic cholecystectomy and preventive measures.
AB  - Spilled gallstones left in the abdominal cavity or trapped at trocar sites may
      cause considerable morbidity. We saw a patient with an abdominal wall abscess 2
      years after laparoscopic cholecystectomy secondary to spilled stones. After we
      reviewed the operative procedure in addition to the accumulated experience in
      laparoscopic surgery, we believe that retrieval of specimens and their contents
      is of paramount importance, especially when the gallbladder is infected, contains
      several stones, or may harbor malignancy. Therefore, we made use of a simple
      surgical glove with a long pursestring suture surrounding the opening to collect
      the specimen. This method proved to be simple and quite convenient, with the
      needed materials readily available. It can collect the spilled stones within the
      abdominal cavity as well as the gallbladder and can transport these stones out of
      the abdominal cavity with ease and safety. It also protects the specimen in
      contact with the wound and cuts short the operating time. The technique and
      advantages are described.

PMID- 11444326
TI  - Physiology of intra-abdominal and intrathoracic Nissen fundoplications in a
      porcine model.
AB  - BACKGROUND: The physiologic competency of intrathoracic fundoplications remains
      controversial. This study compared the physiologic qualities of intra-abdominal
      Nissen fundoplications (IAF) with those of intrathoracic Nissen fundoplications
      (ITF) in a porcine model. METHODS: The lower esophageal sphincter (LES) length
      (cm), LES resting pressure (mm Hg), and intragastric pressure (mm Hg) necessary
      to produce reflux or wrap distribution were manometrically assessed before and
      after IAF and ITF in 10 pigs. Mean +/- SD were compared using analysis of
      variance. RESULTS: There was no difference in LES length before and after IAF or
      ITF, but there was a significant increase in resting LES pressure after eithe

PMID- 11444327
TI  - Effects of topical tumoricidal agents on port-site recurrence of colon cancer: an
      experimental study in rats.
AB  - BACKGROUND: Reports of metastatic spread of colon and rectal cancer to port sites
      after laparoscopic resection of potentially curable lesions has raised doubt
      regarding the efficacy and safety of laparoscopic technology in cancer surgery.
      Experimental study in animals has led us to believe that the mode of spread of
      these metastases is via the direct route. We hypothesized, therefore, that we
      could decrease the rate of trocar-site recurrences by treating the individual
      port sites with a topical tumoricidal agent. MATERIALS AND METHODS: Male BD-IX
      rats weighing 240 to 360 g were injected with syngeneic colon cancer to simulate
      free intraperitoneal cancer spread to trocar sites. All rats were subjected to a
      sham laparoscopic operation after 2 x 10(5) viable cancer cells had been injected
      into their peritoneal cavities. Five-millimeter trocars were inserted into each
      rat after abdominal insufflation to 10 mm Hg. Pneumoperitoneum was maintained for
      10 minutes before the trocars were removed simultaneously. Trocar sites were then
      subjected to one of three treatments, with each animal receiving a maximum of two
      different treatments. Sites were treated with 70% ethanol (N = 42), povidine/
      iodine (N = 40), or no topical treatment (N = 46). Three weeks later, the animals
      were euthanized and autopsied. Subcutaneous tumors at trocar sites or tumors with
      >50% volume within the wound were considered implants. RESULTS: Control sites
      revealed a metastasis rate of 41% (19/46). The tumor implant rate was 36% (15/42)
      at alcohol-treated sites and 20% (8/40) at sites treated with povidone-iodine (P
      < 0.05). CONCLUSION: Topical administration of povidone-iodine to trocar wounds
      after laparoscopic surgery can significantly reduce the incidence of port-site
      metastasis in a syngeneic animal model of colon cancer.

PMID- 11444328
TI  - Framework convention on tobacco control: the way out.

PMID- 11444329
TI  - The outcome of tuberculosis treatment at a rural hospital in southern Ethiopia.
AB  - We evaluated the treatment results of 239 patients with sputum positive pulmonary
      tuberculosis (TB) and describe potential factors associated with reduced
      programme performance in aTB treatment programme in Ethiopia.The TB registry was
      incomplete and 64 (26.8%) patients were not recorded in the control programme. Of
      the 239 patients, 34.3% received short-course chemotherapy (SCC) as a first
      treatment, 5.9% received SCC having previously been treated with standard long
      course chemotherapy (LCC), and 54.4% were initially put on LCC. After excluding
      the 75 patients (31.4%) who were transferred to other health institutions outside
      the control area, 100 (61.0%; 95% CI 53.0-68.4) were cured (22.6%) or completed
      the treatment (38.4%) falling short of the target of 85%. Five months or later
      during treatment 1.8% remained smear-positive, 7.3% died and 29.9% interrupted
      their treatment. Sputum tests were done in 78% of the eligible patients at 2
      months, in 20% at 5 months and in 60.2% at the expected time of treatment
      completion. By July 1998, 5.4% of the patients initially on LCC had relapsed and
      were retreated with SCC. None of those initially cured with SCC needed to be
      retreated. Compared with patients in theTB registry, non-registered patients had
      lower treatment completed and cure rates (42.3% versus 65.2%; P = 0.047), more
      patients were transferred out of the TB programme (59.4% versus 21.1%; P<0.001)
      and the defaulter rate was higher (57.7% versus 24.6%; P=0.002). Weaknesses in
      the programme performance include organizational issues such as the under use of
      theTB registry, deficient follow-up procedures, the common usage of LCC and
      unsatisfactory rates of defaulting.

PMID- 11444330
TI  - A psychiatric ward in an African district hospital.
AB  - In most African district hospitals there are no separate facilities for
      psychiatric patients. Aformer general medical officer describes how a ward for
      these patients was set up at a rural district hospital in Zimbabwe using the
      already available resources. The effects on the psychiatric care at the hospital
      and the district are illustrated by two case reports. It is concluded that
      psychiatric care integrated in primary healthcare, with due regard for the
      cultural aspects and with cooperation of local healers is feasible, provided that
      it is supported by additional diagnostic and treatment facilities at the district
      hospital.

PMID- 11444331
TI  - Shortfalls in the use of adenosine deaminase in tuberculous meningitis.

PMID- 11444332
TI  - Risk factors for severe pneumonia in children in Basrah.
AB  - A case-control study was undertaken in Basrah Maternity and Children Hospital,
      Iraq. We studied 148 children who were admitted to hospital with severe pneumonia
      according to the World Health Organization (WHO) criteria and the controls were
      250 children attending the out-patient department for non-severe respiratory
      infections. Significant risk factors were younger age (2-6 months), low parental
      education, smoking at home, prematurity, weaning from breast milk at < 6 months,
      a negative history of diphtheria, pertussis and tetanus vaccination, anaemia and
      malnutrition.

PMID- 11444333
TI  - Measles vaccine coverage and immune response in children of Caiabi and Metuktire
      Indian tribes living in malarial endemic area: Parque indigena do Xingu, Central
      Brazil.
AB  - Measles vaccination efficiency was evaluated in children from two Indian tribes -
      Caiabi and Metuktire - living in the Amazon region, in the Parque Indigena do
      Xingu (PIX). The population sample, selected at random, made up 37 Caiabi and 28
      Metuktire children, aged from 20-75 months (40%). For operational and
      epidemiological reasons, measles vaccine is given from 6 months of age. The
      average age of children when they received the vaccine was 11.5 months for the
      first dose and 20 months for the second. The search for IgG antibodies against
      measles virus and Plasmodium falciparum was made through immunofluorescence assay
      (IFA). Measles vaccine coverage has reached 60% at 12 months of age and 92% at 18
      months, whereas post-vaccine serum conversion was 95% in Caiabi children
      (geometric mean of titres (GMT) 126) and 89% in Metuktire (GMT 109). The
      difference in GMT is not statistically significant. Seventy-three per cent of
      Caiabi children (GMT 101) and 100% of Metuktire children (GMT135) were plasmodium
      antibody positive, showing they had been exposed to malarial infection. Despite
      the differences detected, the immune response to measles vaccine was satisfactory
      in both groups, with a positive percentage consistent with that achieved in non
      malarial areas in Americas. The results show the efficiency of a vaccination
      programme in an indigenous area despite the difficulties in reaching the villages
      and maintaining the cold chain, and also despite the malaria endemicity.

PMID- 11444334
TI  - MOSHI: a culture-tailored management game for African hospital managers.
AB  - The computer-based management game MOSHI (management of small hospitals) was
      developed in Tanzania and became an integrated component of a training programme
      for East African hospital managers. Players are in charge of a 120-bed hospital
      in rural Tanzania and have to make strategic and tactical decisions according to
      their own traditions and values. Thus, it becomes possible that the cultural gap
      between western management philosophy and traditional African values is bridged.

PMID- 11444335
TI  - Anti-CagA antibodies in Helicobacter pylori-positive patients and blood donors
      from Nigeria.
AB  - The prevalence of antibodies to CagA protein was evaluated in 174 Helicobacter
      pylori-positive. subjects: 110 patients submitted to upper gastrointestinal
      endoscopy and 64 male blood donors. The patients were from different regions of
      Nigeria: Jos, North, Benue,West and East and the blood donors were from Jos. Sera
      were assayed for anti-CagA antibodies using Helicobacter p120, CagA ELISA (Viva
      Diagnostika, Hurth, Germany). Anti-CagA antibodies were detected in 104 (94.5%)
      patients and in 61 (95.3%) blood donors (P=1.0). Patients from the Benue region
      presented a lower frequency of anti-CagA antibodies than patients from the other
      regions (P=0.0004). When the subjects were stratified by age, a significant
      increase in IgG concentration was observed among the men (P=0.03) but not among
      the women (P=0.57) or among the blood donors (P=0.83). In conclusion, similarly
      toAsian countries, CagA-positive H. pylori infection is highly frequent in
      Nigeria.

PMID- 11444336
TI  - Metabolic complications of organophosphate and carbamate poisoning.
AB  - The clinical manifestations of acute organophosphate (OP) and carbamate poisoning
      have already been well described. Most of these reports were on the cardiac,
      neurologic, respiratory and other clinical complications of these compounds.
      However, very little attention has been given to the metabolic aspects of this
      problem, particularly those accompanying carbamate poisoning. This paper
      describes the metabolic complications seen in 84 adult patients after acute
      poisoning with these compounds.

PMID- 11444337
TI  - Results of group-circumcision of Muslim boys in Malaysia with a new type of
      disposable clamp.
AB  - This study evaluates the safety and results of surgery usingTaraKlamp
      Circumcision Device during a group circumcision. Atotal of 64 circumcisions of
      Muslim boys were performed by Medical Assistants supervised by Medical Doctors in
      a hall in Kuala Lumpur, Malaysia. A new type disposable clamp was used, which was
      removed 4 days after the operation. No major complications occurred and the boys
      experienced in general mild pain postoperatively. Mostly good cosmetic results
      were obtained and 90% of the parents would recommend this new clamp to others.
      Group circumcisions withTaraKlamp Circumcision Device (Kuala Lumpur, Malaysia)
      are safe, although proper patient selection and adequate training in using the
      device are mandatory.

PMID- 11444338
TI  - Pyomyositis in adults: a 12 year review.
AB  - From January 1988 to December 1999, 43 adults with pyomyositis were managed at
      Ahmadu Bello UniversityTeaching Hospital, Zaria, Nigeria. Staphylococcus
      aureuswas the most commonly cultured organism (92.5%). All the 41 patients
      responded well to incision and adequate drainage, antibiotics and partial
      thickness skin grafting in 10 patients (23.2%).Two patients (4.65%) died from
      septicaemia, while being resuscitated.

PMID- 11444339
TI  - Thyroid function testing in eastern Nepal and the impact of CME on subsequent
      requests.
AB  - This study reveals 1 year's experience of the introduction of thyroid function
      tests (TFT) in B P Koirala Institute of Health Sciences (BPKIHS), a Medical
      University situated in eastern Nepal. These were performed on theadvice of
      doctors working in this region. The rational TFT advice by the medical
      practitioners was evaluated according to how closely the advice was in line with
      the algorithms recommended in the textbooks. Only about 14% of the TFT advice
      followed some rational strategy. A retrospective analysis showed that rational
      TFT advice could have reduced the cost of a TFT investigation to 43.11% without
      altering the patient management and disease outcome. Continuing medical education
      (CME) lectures arranged for a limited number of doctors were found to improve the
      quality of the subsequentTFT advising pattern. This emphasizes the importance of
      CME while introducing a costly laboratory test panel (e.g.TFT, lipid profile)
      needing a strategic approach.

PMID- 11444340
TI  - The use of misoprostol for mid-trimester therapeutic termination of pregnancy.
AB  - Extra-amniotic prostaglandin F2alpha (PG F2alpha) is probably the most widely
      used medical method for mid-trimester termination of pregnancy. The method is
      highly effective but is financially costly, particularly for poor countries faced
      with restricted health budgets. The aim of this study was to establish whether
      misoprostol administered vaginally is as effective as PG F2alpha. Sixty-one
      patients were prospectively randomized to receive either misoprostol (n=30)
      vaginally, or PG F2alpha (n=31) extra-amniotically. The overall success rate was
      83.6%. The success rates in the misoprostol and PG F2alpha groups were 83.3% and
      83.8% respectively. There was no statistical difference in the groups in relation
      to side effects. In this carefully selected group of patients, misoprostol was as
      safe and effective as PG F2alpha in mid-trimester termination of pregnancy. In
      these days of financial constraints, misoprostol is the preferred method for mid
      trimester termination of pregnancy.

PMID- 11444341
TI  - Maternal comprehension of home-based growth chart in Bahrain.
AB  - The objectives of this study were to assess Bahrain mothers' understanding and
      interpretation of currently used home-based growth monitoring chart, and how
      their education effects their comprehension of it. A sample of 472 mothers of
      children who were less than 6 years old were selected from 18 health centres in
      Bahrain. About 73% brought the growth chart with them during their visits. The
      education of the mothers had a significant effect on the comprehension of the
      growth chart. Highly-educated mothers were more likely to read the information in
      the growth chart (69%) than middle (52%) and low-educated mothers (16%)
      (P<0.0001). Also highly-educated mothers got more benefit from the growth chart
      (P<0.0001) and more of them understood the reason for the colour in the chart
      (P<0.0001) than other groups. The majority of husbands (85%) showed no interest
      in reading the growth chart. Of the mothers, 42% did not know at which age the
      growth chart should be used. It is important, therefore, that the current growth
      chart should be reviewed and the mothers and health workers should be involved in
      the process of designing the chart. Suggestions for improvement of the growth
      chart currently used were provided.

PMID- 11444342
TI  - The improvised atraumatic suture: a cost-reducing technique, not only for the
      tropics?
AB  - A simple technique to produce your own atraumatic suture is described. All that
      is needed is a simple injection needle and any kind of thread.The thread is
      introduced into the cavity of the needle and fixed by squeezing its end after
      having broken the hub. This method is very easy to apply and extremely
      economical.

PMID- 11444343
TI  - Microbial keratitis in eastern Nepal.

PMID- 11444344
TI  - Declining trend of rheumatic fever observed in Bangladesh, 1991-1997.

PMID- 11444345
TI  - Copper sulphate densitometry: a screening tool for anaemia in rural antenatal
      clinics.

PMID- 11444346
TI  - Emergency craniotomy using improvised instruments.

PMID- 11444347
TI  - Stingray injury of the hand: review of management.

PMID- 11444348
TI  - New challenges in tropical medicine and parasitology.

PMID- 11444349
TI  - The treatment of severe burns of head, hands and feet.

PMID- 11444350
TI  - Statement on the hypothesis that an experimental polio vaccine was origin of HIV.
      World Health Organization Communications Office.

PMID- 11444351
TI  - Malaria: major killer in Africa--but bednets can save lives. Roll Back Malaria.

PMID- 11444352
TI  - Chronic subdural haematoma in two patients with HIV infection.

PMID- 11444353
TI  - Hepatitis C virus infection: a disease of poverty.

PMID- 11444354
TI  - Treatment of vaginal discharge in South Asia.

PMID- 11444355
TI  - Resurgence of schistosomiasis mansoni in Oman.

PMID- 11444356
TI  - Could cultural scarification contribute to the high prevalence of HIV in central
      Africa?

PMID- 11444357
TI  - Anthropometric measurements in children with congenital heart disease.

PMID- 11444358
TI  - Consensus on use of co-trimoxazole.

PMID- 11444359
TI  - Norwegian Agency for International Development (NORAD).

PMID- 11444360
TI  - Transient hyperinsulinism in an asphyxiated newborn infant with hypoglycemia.
AB  - We describe a case of transient hyperinsulinism in an asphyxiated newborn infant
      with hypoglycemia. Although hypoglycemia in birth asphyxiated infants is
      generally attributed to depletion of glycogen stores, we observed severe
      hyperinsulinism associated with the hypoglycemia. The hypoglycemia was refractory
      to high glucose delivery rates (25 mg/kg/min), but responded to a combination of
      octreotide and diazoxide. At 3 weeks of age, the medications were discontinued
      and infant was normoglycemic on glucose infusion rates of 5-8 mg/kg/min.
      Subsequent insulin studies were within normal limits. Transient hyperinsulinism
      should be considered in asphyxiated infants with protracted hypoglycemia and
      medications designed to suppress insulin secretion may be useful in refractory
      cases.

PMID- 11444361
TI  - Chromosomal mosaicism in a pregnant woman treated with acyclovir for herpes
      simplex encephalitis.
AB  - At 17th week of pregnancy, a 28-year-old woman was diagnosed as having herpes
      simplex encephalitis and treated with intravenous acyclovir. Follow-up by the
      serial ultrasound examinations, intrauterine growth retardation (IUGR) was found.
      During the course of disease, cordocentesis was performed to evaluate the risk of
      the disease and the infant's chromosomal constitution. No herpes simplex virus
      infection on cord blood sample was observed; however, chromosomal analysis
      revealed: 46,XX/47,XX,+2/47,XX,+11/47,XX,+19/48,XX,+11. After termination of
      pregnancy, the fetus was found as having ventricular septum defect. The presence
      of the triploid cell lines mocaicism involving chromosome 2 and 19 were confirmed
      by the analysis of fetal skin tissues. No attributable finding to herpes simplex
      virus infection and acyclovir treatment was found, and the presence of the
      triploid cell lines mocaicism were appeared to be purely coincidental.

PMID- 11444362
TI  - Cerebral blood flow velocity acutely decreases in newborns who respond to inhaled
      nitric oxide.
AB  - Regional cerebral blood flow is directly proportional to the Doppler velocity
      time integral of flow in corresponding cerebral arteries. This study was
      performed to determine whether an acute change in the velocity time integral of
      cerebral blood flow occurs in newborns with pulmonary hypertension who experience
      an acute improvement in pulmonary hemodynamics and gas exchange at the onset of
      inhaled nitric oxide therapy. Twenty-two newborns with lung disease and an
      oxygenation index >25 were treated with 10 to 20 parts per million inhaled nitric
      oxide. Measurements of heart rate, blood pressure, arterial blood gases, right
      and left ventricular planimetry, and Doppler ultrasonography were performed
      before and after 30 to 60 minutes of therapy. Nitric oxide inhalation was
      associated with a significant acute change in arterial blood pressure, pH,
      arterial carbon dioxide tension, arterial oxygen tension, proportion of right-to
      left ductal shunt, estimated systolic pulmonary arterial pressure, and right
      ventricular diastolic and systolic areas. In the middle cerebral artery, peak
      systolic flow velocity (49+/-5 vs. 41+/-4, cm/sec), diastolic flow velocity (21+/
      3 vs. 14+/-3, cm/sec), and the velocity time integral (10.3+/-1.1 vs. 7.9+/-1.1,
      cm) all decreased (p<0.05). These changes only occurred in a subgroup of 17
      patients who experienced an improvement in arterial oxygen tension > or =10 mm
      Hg. The velocity time integral of flow in the middle cerebral artery is acutely
      decreased in newborns with pulmonary hypertension who experience an acute
      increase in oxygenation after the onset of inhaled nitric oxide.

PMID- 11444363
TI  - Influence of hemostatic factors on spontaneous abortion.
AB  - To assess the relationship between hemostatic factors and spontaneous abortion,
      134 pregnant women presenting to the emergency department were recruited and
      followed through 22 weeks' gestation. Cases were women experiencing a spontaneous
      abortion and controls were women who maintained their pregnancy. Fibrinogen,
      factor VII antigen, activated protein C-sensitivity ratio (APC-SR), protein S,
      and plasmin-antiplasmin (PAP) were measured. Cases had lower mean levels of
      fibrinogen and factor VII antigen compared with controls (3.1 g/L vs. 3.7 g/L and
      89% of normal vs. 109% of normal, respectively). Regression analyses found that
      women with fibrinogen levels below 3.0 g/L had a five-fold increased risk of
      spontaneous abortion (OR = 5.1, 95% CI: 1.8-14.4) and women with factor VII
      antigen levels below 94% of normal had a threefold increased risk of spontaneous
      abortion normal (OR = 3.3, 95% CI: 1.2-8.5). Similar mean levels of APC-SR,
      protein S, and PAP were found in the two groups.

PMID- 11444364
TI  - Three-dimensional measurement of gestational and yolk sac volumes as predictors
      of pregnancy outcome in the first trimester.
AB  - Along with crown-rump length (CRL), the size (diameter) of embryonic structures
      such as gestational sac (GS) and yolk sac (YS) may have prognostic value for
      embryonic development. We proposed that first-trimester volume calculations of
      these structures using transvaginal three-dimensional ultrasound technique may
      have value as predictors of adverse reproductive outcome. Forty-nine consecutive
      patients (treated for infertility) with singleton pregnancies were included in
      this prospective study. Seventy-three examinations were performed in case of
      pregnancies with normal, and 12 with abnormal outcome. GS and YS volumes were
      plotted against gestational age (GA) (25-65 days post ovulation) to create
      nomograms for normal outcome and the same procedure was carried out with CRL
      measurements as well. Measurements of abnormal pregnancies were compared with
      these nomograms. Specificity, sensitivity, positive and negative predictive
      values were also calculated. Regression analysis revealed a power correlation
      between GS volumes and GA, logarithmic relationship was observed when YS volumes
      were plotted against GA. CRL showed logarithmic correlation with GA as well. Both
      GS volumetry and CRL measurements proved to have statistically significant
      predictive value for adverse outcome (p<0.05). However, no statistically
      significant difference was found when YS volumes of normal and abnormal
      pregnancies were compared. Specificity, sensitivity, positive and negative
      predictive values of GS volumes and CRL were similar. Mean YS/GS ratios also had
      good predictive values (p<0.05). Volume determination of YS and GS can be
      performed quickly and simply applying three-dimensional sonography. Volumetry of
      GS proved to be a sensitive predictor for pregnancy outcome and can be a good 
      supplement to CRL measurements.

PMID- 11444365
TI  - A case of acute inflammatory demyelinating polyradiculoneuropathy in early
      pregnancy.
AB  - Acute or chronic inflammatory demyelinating polyradiculoneuropathy is a rare
      disorder that presents with weakness, hyporeflexia, and sensory loss. Treatment
      consists of immunosuppression and/or plasma exchange. A woman in the first
      trimester of pregnancy presents with flaccid quadriplegia and numbness.
      Electromyography demonstrated a demyelinating polyneuropathy with active
      denervation. The diagnosis of acute inflammatory demyelinating
      polyradiculoneuropathy was made. She was treated with corticosteroids and
      plasmapheresis. Despite slow improvement, she decided to terminate the pregnancy
      at 18 weeks' gestation. At 1 year postpartum she is still in remission.
      Inflammatory demyelinating polyradiculoneuropathy should be considered in the
      differential diagnosis of every pregnant woman with new onset peripheral
      neuropathy. It is suggested that relapse occurs three times more common during
      pregnancy. Plasmapheresis is the recommended treatment.

PMID- 11444366
TI  - Ultrasonographic femur-tibial length ratio: a marker of Down syndrome from the
      late second trimester.
AB  - An observational prospective study reported that newborn babies with Down
      syndrome (DS) had short upper limbs that reach up to their pelvis. The shortening
      was most marked in the forearm (the middle segment of the upper limb) and this
      relative shortening resulted in an alteration of the proximal to middle segment
      length ratio. This study assumes that there is a similar alteration in the ratio
      of the lower limb. We propose to study the proximal to middle segment ratio in
      the lower limb in normal fetuses at different gestational ages. Against these
      norms we propose to study the ratio in fetuses with DS to see at what stage in
      intrauterine life the altered ratio becomes evident. We also propose to take
      postnatal measurements of upper and middle segments of both upper and lower limbs
      of babies born with DS and compare them with normal babies. Fetal femoral and
      tibial lengths were measured by routine antenatal ultrasound scans at a General
      hospital with 6000 deliveries a year. All babies delivered were examined for
      phenotypical evidence of DS. The in utero measurements recorded of babies born
      with DS were compared with the measurements in normal babies. Postnatal
      measurements of the arm and forearm, and the thigh and leg of babies with DS were
      taken soon after birth. These were compared with a control group of 20
      consecutive normal babies born over 2 days. There were 3690 readings of 3075
      normal fetuses and 8 measurements of 7 Down fetuses. The leg, the upper arm, and
      arm of newborns with DS were significantly shorter than controls (p<0.01). The
      upper limb reached up to the pelvis in infants with DS and not up to mid thigh as
      in normal babies. The forearm was shorter than the arm in infants with DS. This
      is a reversal of the ratio seen in controls. The ratio of femoral to tibial
      length remains near constant at 1.1 after 13 weeks' gestation in normal fetuses.
      It rises from 1.2 to 1.4 from 22 weeks' to 38 weeks' gestation in fetuses with
      DS. The mean standard deviation score of fetuses with DS was 4.53 compared with
      norms (SD 1.7, p<0.01). Conclusions of this study are: (1) short upper limbs
      (reaching only up to the pelvis) is a clinical feature of DS at birth; and (2)
      after 20 weeks' gestation, the ratio of femoral-tibial length can be a marker of
      DS in utero.

PMID- 11444367
TI  - Maternal and neonatal outcome of 100 consecutive triplet pregnancies.
AB  - The objective of this study is to determine the maternal and neonatal outcome of
      a large group of triplet gestations. A retrospective review of 100 triplet
      gestations managed and delivered between January 1992 and September 1999 by a
      single perinatal group is examined. These pregnancies were managed on an
      outpatient basis. Prophylactic interventions were not utilized. Ninety-six
      percent of the pregnancies had at least one complication, with preterm labor the
      most common. The median gestational age at delivery was 33 weeks (range 20.4 to
      37, SD 4.1 weeks) with 14% of pregnancies delivering prior to 28 weeks'
      gestation. The corrected perinatal mortality rate was 97/1000. Minimal long-term
      morbidity was seen with delivery after 27 weeks' gestation. Pregnancy outcome did
      not vary with birth order or mode of conception. Triplet pregnancy is associated
      with a high rate ofantenatal complications. Favorable neonatal outcome can be
      obtained without the use of prophylactic interventions.

PMID- 11444368
TI  - The first example of a Hoogsteen base-paired DNA duplex in dynamic equilibrium
      with a Watson-Crick base-paired duplex--a structural (NMR), kinetic and
      thermodynamic study.
AB  - A single-point substitution of the O4' oxygen by a CH2 group at the sugar residue
      of A6 (i.e. 2'-deoxyaristeromycin moiety) in a self-complementary DNA duplex, 5'
      d(C1G2C3G4A5A6T7T8C9G10C11G12)2(-3), has been shown to steer the fully Watson
      Crick basepaired DNA duplex (1A), akin to the native counterpart, to a doubly
      A6:T7 Hoogsteen basepaired (1B) B-type DNA duplex, resulting in a dynamic
      equilibrium of (1A)<==>(1B): Keq = k1/k(-1) = 0.56+/-0.08. The dynamic conversion
      of the fully Watson-Crick basepaired (1A) to the partly Hoogsteen basepaired (1B)
      structure is marginally kinetically and thermodynamically disfavoured [k1 (298K)
      = 3.9 0.8 sec(-1); deltaHdegrees++ = 164+/-14 kJ/mol; -TdeltaS degrees++ (298K) =
      -92 kJ/mol giving a deltaG degrees++ 298 of 72 kJ/mol. Ea (k1) = 167 14 kJ/mol]
      compared to the reverse conversion of the Hoogsteen (1B) to the Watson-Crick (1A)
      structure [k-1 (298K) = 7.0 0.6 sec-1, deltaH degrees++ = 153 13 kJ/mol; 
      TdeltaSdegrees++ (298K) = -82 kJ/mol giving a deltaGdegrees++(298) of 71 kJ/mol.
      Ea (k-1) = 155 13 kJ/mol]. Acomparison of deltaGdegrees++(298) of the forward
      (k1) and backward (k-1) conversions, (1A)<==>(1B), shows that there is ca 1
      kJ/mol preference for the Watson-Crick (1A) over the double Hoogsteen basepaired
      (1B) DNA duplex, thus giving an equilibrium ratio of almost 2:1 in favour of the
      fully Watson-Crick basepaired duplex. The chemical environments of the two
      interconverting DNA duplexes are very different as evident from their widely
      separated sets of chemical shifts connected by temperature-dependent exchange
      peaks in the NOESY and ROESY spectra. The fully Watson-Crick basepaired structure
      (1A) is based on a total of 127 intra, 97 inter and 17 cross-strand distance
      constraints per strand, whereas the double A6:T7 Hoogsteen basepaired (1B)
      structure is based on 114 intra, 92 inter and 15 cross-strand distance
      constraints, giving an average of 22 and 20 NOE distance constraints per residue
      and strand, respectively. In addition, 55 NMR-derived backbone dihedral
      constraints per strand were used for both structures. The main effect of the
      Hoogsteen basepairs in (1B) on the overall structure is a narrowing of the minor
      groove and a corresponding widening of the major groove. The Hoogsteen
      basepairing at the central A6:T7 basepairs in (1B) has enforced a syn
      conformation on the glycosyl torsion of the 2'-deoxyaristeromycin moiety, A6, as
      a result of substitution of the endocyclic 4'-oxygen in the natural sugar with a
      methylene group in A6. A comparison of the Watson-Crick basepaired duplex (1A) to
      the Hoogsteen basepaired duplex (1B) shows that only a few changes, mainly in
      alpha, sigma and gamma torsions, in the sugar-phosphate backbone seem to be
      necessary to accommodate the Hoogsteen basepair.

PMID- 11444369
TI  - Branched nanowire based guanine rich oligonucleotides.
AB  - Self-assembly and aggregation of guanine rich sequences can provide useful
      insights into DNA nanotechnology and telomeric structure and function. In this
      paper, we designed a guanine rich sequence d(GGCGTTTTGCGG). We found that it can
      form stable structure in appropriate condition and it exhibits an anomalous CD
      spectra. This structures can be imaged in ambient environment with a Nanoscope
      III AFM (Digital Instruments). We found it forms branch structure and long
      multistrand DNA nanowire after incubation at 37 degrees C for 6-12 hours in 25 mM
      TE (pH=8.0) + 5 mM Mg2+ + 50 mM K+. The ability to self-assemble into branches
      and long wires not only clearly demonstrate its potential as scaffold structures
      for nanotechnology, but also give aids to understand telomeric structure further.
      We have proposed a model to explain how these structures formed.

PMID- 11444370
TI  - Comparison of complex DNA mixtures with generic oligonucleotide microchips.
AB  - The reproducibility of melting curves for repeated hybridizations of target DNA
      with generic oligonucleotide microchips is shown experimentally to depend on the
      character of matching between fragments of target DNA and immobilized
      oligonucleotides. The reproducibility of melting curves is higher for the perfect
      match duplexes and decreases as the number of mismatched pairs within duplexes
      increases. This effect was applied to the comparative analysis of complex DNA
      mixtures. We developed a scheme in which we can identify and discriminate between
      the probe oligonucleotides responsible for the distinctions between target DNA
      mixtures. A scheme is illustrated by comparing DNA mixtures corresponding to V-D
      J genes connected with populations of mRNAs CDR3 TCR Vb (T-cell receptor beta
      complementarity determining region 3) from the thymus and pancreas of NOD mice.
      Our results demonstrate that generic microchips can be applied efficiently to the
      analysis of DNA mixtures.

PMID- 11444371
TI  - The occurence of the syn-C3' endo conformation and the distorted backbone
      conformations for C4'-C5' and P-O5' in oligo and polynucleotides.
AB  - The nucleoside constituents of nucleic acids prefer the anti conformation (1).
      When the sugar pucker is taken into account the nucleosides prefer the C2'endo
      anti conformation. Of the nearly 300 nucleosides known, about 250 are in the anti
      conformation and 50 are in the syn-conformation, i.e., anti to syn conformation
      is 5:1. The nucleotide building blocks of nucleic acids show the same trend as
      nucleosides. Both the deoxy-guanosine and riboguanosine residues in nucleosides
      and nucleotides prefer the syn-C2'endo conformation with an intra-molecular
      hydrogen bond (for nucleosides) between the O5'-H and the N3 of the base and, a
      few syn-C3'endo conformations are also observed. Evidence is presented for the
      occurrence of the C3'endo-syn conformation for guanines in mis-paired double
      helical right-handed structures with the distorted sugar phosphate C4'-C5' and P
      O5' bonds respectively, from g+ (gg) and g- to trans. Evidence is also provided
      for guanosine nucleotides in left-handed double-helical (Z-DNA) oligo and
      polynucleotides which has the same syn-C3'endo conformation and the distorted
      backbone sugar-phosphate bonds (C4'-C5' and P-O5') as in the earlier right-handed
      case.

PMID- 11444372
TI  - Molecular dynamics studies of sequence-directed curvature in bending locus of
      trypanosome kinetoplast DNA.
AB  - The macroscopic curvature induced in the double helical B-DNA by regularly
      repeated adenine tracts (A-tracts) plays an exceptional role in structural
      studies of DNA because this effect presents the most well documented example of
      sequence specific conformational modulations. Recently, a new hypothesis of its
      physical origin has been put forward. According to it, the intrinsic bends in B
      DNA may represent one of the consequences of the compressed frustrated state of
      its backbone. The compressed backbone hypothesis agrees with many data and
      explains some controversial experimental observations. The original arguments of
      this theory came out from MD simulations of a DNA fragment with a strong bending
      propensity. Its sequence, however, was not experimental. It was constructed
      empirically so as to maximize the magnitude of bending in calculations. To make
      sure that our computations reproduce the experimental effect we carried out
      similar simulations with an A-tract repeat of a natural base pair sequence found
      in a bent locus of a minicircle DNA. We demonstrate spontaneous development of
      static curvature in the course of MD simulations excluding any initial bias
      except the base pair sequence. Its direction and magnitude agree with
      experimental estimates. The results confirm earlier qualitative conclusions and
      agree with the hypothesis of a compressed backbone as the origin of static
      bending in B-DNA.

PMID- 11444373
TI  - Investigation of DNA binding modes for a symmetrical cyanine dye trication:
      effect of DNA sequence and structure.
AB  - The DNA binding behavior of a tricationic cyanine dye (DiSC3+(5)) was studied
      using the [Poly(dA-dT)]2, [Poly(dI-dC)]2 and Poly(dA) x Poly(dT) duplex sequences
      and the Poly(dA) x 2Poly(dT) triplex. Optical spectroscopy and viscometry results
      indicate that the dye binds to the triplex structure by intercalation, to the
      nonalternating Poly(dA) x Poly(dT) duplex through minor groove binding and to the
      alternating [Poly(dA-dT)]2 duplex by a combination of two binding modes:
      intercalation at low concentration and dimerization within the minor groove at
      higher concentration. Dimerization occurs at lower dye concentrations for the
      [Poly(dI-dC)]2 sequence, consistent with our previous investigations on an
      analogous monocationic cyanine dye. [Seifert, J.L., et al. (1999) J. Am. Chem.
      Soc. 121, 2987-2995] These studies illustrate the diversity of DNA binding modes
      that are available to a given ligand structure.

PMID- 11444374
TI  - Unusual DNA binding exhibited by synthetic distamycin analogues lacking the N
      terminal amide unit under high salt conditions.
AB  - The binding of three analogues of the minor-groove binding antiviral antibiotic
      distamycin (Dst) with double-stranded (ds)-DNA were monitored using ds-DNA
      melting temperature (Tm) measurements, ethidium bromide (EtBr) displacement
      assay, footprinting analysis and induced circular dichroism (ICD). These
      compounds contained 3-5 N-methyl-pyrrole-carboxamide units and lacked the N
      terminal formamide unit present in Dst. These experiments suggested that the
      present analogues did not compromise their AT-specificity despite the deletion of
      the N-terminal formamide unit. The binding affinities, however, were
      significantly affected. Interestingly, the analogue with three N-methyl-pyrrole
      carboxamide units exhibited an initial decrease in ICD at > 40 mM salt
      concentrations. This was followed by a pronounced recovery of ICD at > 1.6 M salt
      concentrations, a phenomenon hitherto not observed with any other DNA binding
      molecules. The pentapyrrole analogue exhibited the highest binding affinity with
      CT-DNA under normal (40 mM) salt conditions. However, it suffered maximum
      relative dissociation under high salt conditions and did not exhibit any recovery
      in ICD at higher NaCl concentrations. The analogues possessing four and five
      pyrrole rings exhibited intense ICD signals with poly d(GC) in the ligand
      absorption region in the presence of 40 mM NaCl, unlike the one with three
      pyrrole rings. These ICD signals were however, highly susceptible to changes in
      ionic strength. Thus subtle modifications in the ligand molecular structure can
      have dramatic effect on their DNA binding properties.

PMID- 11444375
TI  - Analysis of the codon usage pattern in the Vibrio cholerae genome.
AB  - The codon usage in the Vibrio cholerae genome is analyzed in this paper. Although
      there are much more genes on the chromosome 1 than on chromosome 2, the codon
      usage patterns of genes on the two chromosomes are quite similar, indicating that
      the two chromosomes may have coexisted in the same cell for a very long history.
      Unlike the base frequency pattern observed in other genomes, the G+C content at
      the third codon position of the V. cholerae genome varies in a rather small
      interval. The most notable feature of codon usage of V. cholerae genome is that
      there is a fraction of genes show significant bias in base choice at the second
      codon position. The 2,006 known genes can be classified into two clusters
      according to the base frequencies at this position. The smaller cluster contains
      227 genes, most of which code for proteins involved in transport and binding
      functions. The encoding products of these genes have significant bias in amino
      acids composition as compared with other genes. The codon usage patterns for the
      1,836 function unknown ORFs are also analyzed, which is useful to study their
      functions.

PMID- 11444376
TI  - Electronic properties of the amino acid side chains contribute to the structural
      preferences in protein folding.
AB  - A database of 118 non-redundant proteins was examined to determine the
      preferences of amino acids for secondary structures: alpha-helix, beta-strand and
      coil conformations. To better understand how the physicochemical properties of
      amino acid side chains might influence protein folding, several new scales have
      been suggested for quantifying the electronic effects of amino acids. These
      include the pKa at the amino group, localized effect substituent constants
      (esigma), and a composite of these two scales (epsilon). Amino acids were also
      classified into 5 categories on the basis of their electronic properties: O
      (strong electron donor), U (weak donor), Z (ambivalent), B (weak electron
      acceptor), and X (strong acceptor). Certain categories of amino acid appeared to
      be critical for particular conformations, e.g., O and U-type residues for alpha
      helix formation. Pairwise analysis of the database according to these categories
      revealed significant context effects in the structural preferences. In general,
      the propensity of an amino acid for a particular conformation was related to the
      electronic features of the side chain. Linear regression analyses revealed that
      the electronic properties of amino acids contributed about as much to the folding
      preferences as hydrophobicity, which is a well-established determinant of protein
      folding. A theoretical model has been proposed to explain how the electronic
      properties of the side chain groups might influence folding along the peptide
      backbone.

PMID- 11444377
TI  - The role of surfactant-associated protein A in pulmonary host defense.
AB  - Resident alveolar macrophages play a key role in the initial defense against
      inhaled pathogens. Surface molecules bind opsonized as well as nonopsonized
      microbes and mediate their internalization by the macrophage. The recent
      discovery that specific C-type lectins can bind to the surface of a wide range of
      pathogens has led to the hypothesis that these lectins are involved in the
      initial phases of microbe recognition by the macrophage. Studies in our
      laboratory focus on the role of the lung-specific lectin surfactant associated
      protein A (SP-A) in host defense against pulmonary pathogens. SP-A contains a
      carbohdyrate recognition domain that appears to bind specifically to exposed
      carbohydrate residues on the surface of microorganisms. This lectin-microorganism
      interaction leads to entry of specific pathogens into macrophages and activation
      of intracellular pathways, resulting in the production of antimicrobial mediators
      such as nitric oxide. Many studies, including those involving SP-A-deficient
      mice, underscore the importance of this protein in pulmonary innate immunity.
      However, the intramacrophage mechanisms underlying the effects of SP-A are still
      unclear. This article describes our current knowledge of SP-A and its
      interactions with immune cells and pathogens with a focus on recent findings from
      our laboratory regarding SP-A interactions with mycobacteria.

PMID- 11444378
TI  - Regulation of antigen receptor gene assembly in lymphocytes.
AB  - Somatic alterations affecting the mammalian genome occur exclusively in B and T
      cells. Developing lymphocytes employ a series of DNA recombination events (V(D)J
      recombination) to assemble a diverse repertoire of immunoglobulin (Ig) and T cell
      receptor (TCR) variable regions from a large array of germline gene segments.
      V(D)J recombination is required not only for receptor diversification but also
      for lymphocyte development. At a molecular level, these recombination events are
      directed by conserved DNA sequences flanking all antigen receptor gene segments
      that function as recognition signals for a single recombinase activity. Despite
      these shared features, recombination events are controlled at the levels of stage
      and tissue-specificity. Our primary research focus is to dissect the mechanisms
      that regulate assembly of antigen receptor loci by rendering certain gene
      segments accessible to a common V(D)J recombinase. This article discusses recent
      discoveries from the author's laboratory that address this long-standing issue.
      We have found that transcriptional promoters are critical cis-acting regulatory
      elements for targeting efficient recombination of chromosomal gene segments. We
      have also demonstrated that activation of NF-kappaB signaling in precursor B
      cells is required for global regulation of Ig light chain gene assembly.
      Together, these findings provide key insights into the genetic mechanisms that
      regulate antigen receptor diversity and the developmental pathways leading to the
      acquisition of lymphocyte effector function.

PMID- 11444379
TI  - Genetic and structural determinants of virus neutralizing antibodies.
AB  - Neutralizing antibodies (Abs) are the principal protective mechanism against
      disease caused by reinfection with viruses. Ab-mediated neutralization of viruses
      is a complex process comprising multiple mechanisms. Every structural aspect of
      Abs is potentially capable of modulating the level of neutralizing activity or
      the mechanisms of neutralization. The focus of our laboratory is to understand
      the genetic and structural basis of Ab-mediated neutralization of human viral
      pathogens. We demonstrated the unexpected finding that virus antigen-binding
      fragments of Abs (Fabs) mediate potent virus neutralizing effects in vivo. This
      work has led to a broad investigation of the importance of the genetics,
      chemistry, and structure of the combining site to the neutralizing activity of
      antiviral Abs. Ongoing work in our laboratory reveals that effect or functions
      specified by the Ab isotype such as polymer formation, interactions with
      complement, interactions with Fc receptors, and the ability to transcytose
      mucosal epithelia, also modulate the mechanism and level of neutralizing effects
      mediated by antiviral Abs.

PMID- 11444380
TI  - Regulation of B lymphocyte development and activation by Bruton's tyrosine
      kinase.
AB  - The generation and maintenance of B lymphocytes is controlled by biochemical
      signals transmitted by the B cell antigen receptor(BCR) complex. These signals
      are transduced by multiple cytoplasmic protein tyrosine kinases (PTKs) including
      Lyn, Syk, and Bruton's tyrosine kinase (BTK). Upon BCR engagement, these PTKs
      activate downstream effectors, including transcription factors that modulate gene
      expression. In turn, activation of downstream effectors is critical for B cell
      survival, cell cycle progression, and antibody production. Our studies focus on
      the role of BTK in these biological responses. We have discovered that BTK is
      required for activation of the BCR-responsive transcription factor, NF-kappaB.
      Furthermore, BTK-dependent activation of NF-kappaB is essential for reprogramming
      the expression of genes that control B cell survival and proliferation. The
      biochemical mechanisms by which BTK regulates signaling components that activate
      NF-kappaB, and the identification of BTK-responsive genes are under
      investigation. Elucidation of these regulatory mechanisms is expected to reveal
      new therapeutic targets for B cell pathologies involving defects in BTK,
      including X-linked agammaglobulinemia (XLA).

PMID- 11444381
TI  - Molecular mechanisms in lymphocyte activation and growth.
AB  - Transcription factor NF-kappaB is biochemically coupled to the T cell antigen
      receptor (TCR) and activated transiently during an adaptive immune response. The
      author's laboratory is investigating the signal-dependent regulation of NF
      kappaB, its downstream gene targets, and its function in lymphocyte biology. Our
      studies have revealed novel enzymatic checkpoints in the NF-kappaB signaling
      pathway and constitutive repressors of NF-kappaB that might be clinically
      applicable for therapeutic control of the immune system. We have also found that
      the Tax transforming protein encoded by human T cell leukemia virus type 1
      (HTLV1) binds to and persistently activates an inducible protein kinase in the
      TCR/NF-kappaB axis. This viral/host interaction appears to trigger the
      inappropriate expression of NF-kappaB and the development of HTLV1-associated
      disease.

PMID- 11444382
TI  - T cell signaling mechanisms that regulate HIV-1 infection.
AB  - The ability of human immunodeficiency virus type-1 (HIV-1) to establish a
      persistent infection is critically dependent on the cellular signals that
      regulate HIV-1 replication within target cells. The balance between numerous host
      factors that either enhance or suppress viral infection determines the clinical
      outcome. Perturbation of the steady-state level of viral replication can
      significantly influence the course and the speed at which the infection develops
      into clinical disease. Activation signals delivered to T cells by cytokines and
      antigen-presenting cells (APC), are key modulators of viral replication. Our
      laboratory seeks to decipher how HIV-1 exploits T cell signaling mechanisms and
      host factors that regulate viral replication. Elucidation of the molecular
      mechanisms by which cellular signals regulate the HIV-1 life cycle within target
      cells will significantly advance our understanding of host-virus interactions.

PMID- 11444383
TI  - IL-4 signaling, gene transcription regulation, and the control of effector T
      cells.
AB  - The central goal of our laboratory is to understand the regulation of lymphoid
      cells through molecular mechanisms of signal transduction and transcriptional
      control. A long-standing focus has been on changes that influence the effector
      function of mature lymphocytes. Work in the laboratory is oriented toward the
      identification of new regulatory mechanisms using cell lines and primary cells,
      and the validation of these in vitro findings in mouse models of immune responses
      and diseases. In this review, we summarize key insights into the regulation of T
      helper cell function during the phase of immunity where effector responses arise
      de novo. Particular interest has been centered on cytokine gene regulation as
      part of T cell differentiation into the Th1 and Th2 subsets. Information on IL-4
      receptor signaling and the role of NF-kappaB transcription factors is reviewed.
      Our more recent work is designed to understand how regulation at the Th1/2
      effector stages is related to the control of memory T cell survival, immune
      recall responses, and the role of these responses in immune-mediated disease.

PMID- 11444384
TI  - Transcriptional reprogramming during T helper cell differentiation.
AB  - Our laboratory employs reporter transgenic mice as model systems to study the
      transcriptional reprogramming that accompanies T helper cell differentiation.
      These studies demonstrate that changes in the activity of simple transcriptional
      elements associated with the IFN-gamma gene can recapitulate alterations in gene
      expression. In addition, our studies have revealed a key role for the
      transcription factor, CAMP response element binding protein (CREB), in the
      protection of differentiating T cells from apoptosis. Together, these findings
      further our understanding of the logic employed by T cells to alter gene
      expression profiles in response to differentiation signals.

PMID- 11444385
TI  - Accessory proteins that control the assembly of MHC molecules with peptides.
AB  - The stable assembly of Major Histocompatibility Complex (MHC) molecules with
      peptides is controlled by a number of cofactors, including proteins with general
      housekeeping functions and proteins with dedicated functions in MHC assembly.
      Recent work in my laboratory has focused on two chaperones, tapasin (tpn) and DM,
      that play critical roles in the loading of peptides onto MHC class I and MHC
      class II molecules, respectively. Tapasin is a transmembrane protein that tethers
      empty class I molecules in the endoplasmic reticulum to the transporter
      associated with antigen processing. DM is a peptide exchange factor that binds
      with empty and peptide-loaded class II molecules in endosomal and lysosomal
      compartments. Although a number of different functions for tapasin and DM have
      been proposed, emerging evidence suggests that both of these chaperones retain
      unstable MHC molecules in peptide-loading compartments until they bind with high
      affinity peptides. These cofactors therefore promote the surface expression of
      long-lived MHC-peptide complexes.

PMID- 11444386
TI  - Immune recognition, response, and regulation: how T lymphocytes do it.
AB  - Effective immunity to infectious agents requires the initial recognition of
      antigen by specific receptors, which leads to the activation of immunocytes and
      the elicitation of an immune response. Because T cell antigen recognition and
      directed responses are complex processes, they are initiated and quelled in a
      highly regulated manner. Our laboratory has focused on defining the molecular
      processes that control T cell antigen presentation and recognition. Research in
      this area is focused on determining the chemical nature of antigens displayed by
      Major histocompatibility, complex (MHC)-encoded class I molecules and the
      nonclassical class I-like protein CD1d. Quantitative aspects of antigen
      presentation and recognition are also being studied to determine how these
      factors control the initiation of a T cell response. Our studies provide insights
      into the biochemical basis of T cell antigen recognition and response as well as
      the molecular processes underlying the initiation and regulation of immune
      responses by CD1d-restricted natural T lymphocytes.

PMID- 11444387
TI  - Mucosal T cell response to reovirus.
AB  - During the last three decades, immunologists and gastroenterologists have
      witnessed the formation of mucosal immunology as a discipline in biomedical
      science, and studies of reovirus infection have substantially contributed to this
      evolution. We have focused on mucosal T cell responses induced by reovirus in
      conventional, germfree, nude, and NF-kappaB deficient mice. Several major facets
      of T cell function in the immune responses to this mucosal pathogen have been
      examined, including viral selection of oligoclonal-T cells, extrathymic T cell
      development, and distinct signaling pathways used by CD8 sublineages. In
      addition, our findings with virus-specific T cells selected in the mucosa have
      suggested novel mechanisms for the rearrangement, selection, and expansion of TCR
      genes. With the increasing application of molecular tools, reovirus will continue
      to be a useful model pathogen to study mucosal immunology and will further our
      understanding of mucosal immunity in health and disease.

PMID- 11444388
TI  - Antigen-specific responses in autoimmunity and tolerance.
AB  - Autoantibodies to the hormone insulin arise spontaneously in the insulin
      autoimmune syndrome and in the prodrome of type I diabetes. Further,
      administration of insulin to individuals without autoimmune disease routinely
      results in antibodies that bind autologous hormone. These observations suggest
      that physiological levels of hormones, such as insulin, are below critical
      thresholds for signaling tolerance induction, a state termed clonal ignorance. In
      contrast, studies from our laboratory on the genetic origins and structure of V
      genes used by insulin antibodies suggest that the anti-insulin repertoire is
      tightly regulated. We have shown that B cells in mice harboring an insulin
      antibody transgene are functionally silenced. These findings verify that
      tolerance is active for small molecules, even when they are present at low
      concentrations. Despite active tolerance, insulin antibodies are sustained in the
      repertoire of normal animals by several mechanisms, including activation by TI
      antigen signals, unique display of conformational epitopes, and the recruitment
      of B cells previously selected by responses to other antigens. This essay reviews
      our current understanding of escape pathways for anti-insulin B cells.

PMID- 11444389
TI  - Immunotherapy of inflammatory demyelinating diseases of the central nervous
      system.
AB  - Inflammatory demyelinating diseases comprise a heterogeneous group of disorders
      that affect the peripheral and central nervous system. Multiple sclerosis (MS) is
      the most common disease affecting the CNS white matter. Close similarities
      between MS and the animal model of the disease, experimental allergic
      encephalitis (EAE), have suggested that MS might be an autoimmune disease, which
      is triggered by an infectious agent. Our laboratory has directed its effort in
      identifying and designing therapies that interfere with key signaling pathways
      that mediate CNS inflammation in experimental allergic encephalitis. These have
      included naturally occurring cytokines such as TGFbeta and synthetic small
      molecules, lysofyline and tyrphostin, which inhibit the inflammatory response and
      prevent the development of EAE.

PMID- 11444390
TI  - CD40-ligand in primate cardiac allograft and viral immunity.
AB  - Our laboratory has studied the role of CD40 ligand (CD40L, CD154) in the primate
      immune response to allogenic and infectious challenges. We find that intensive
      early blockade of CD40L reliably attenuates acute rejection of primate cardiac
      allografts. Monotherapy fails to prevent late graft loss, which often occurs in
      association with rising antidonor antibody titers and allograft vasculopathy,
      despite continuing anti-CD40L therapy. In contrast, the primary humoral response
      to T helper dependent influenza viral antigen is inhibited during anti-CD40L
      therapy, and responses to subsequent immunization are blunted after
      discontinuation of therapy. These results are encouraging with regard to the
      tolerogenic potential of costimulatory blockade for specific T helper dependent
      antigens. However, these findings also indicate that pathogenic allograft
      responses in primates are probably not entirely CD40L-dependent. As such,
      additional immunomodulatory strategies are needed to facilitate tolerance to a
      transplanted organ.

PMID- 11444391
TI  - VEGF as a mediator of tumor-associated immunodeficiency.
AB  - Decreased immune function in cancer patients is well-characterized (1), and tumor
      cells have developed a variety of mechanisms to avoid anti-tumor immune responses
      (2-8). One mechanism for inhibition of immune cell function by tumors is the
      production of soluble factors, such as IL- 10, TNF, TGF-beta, and Vascular
      Endothelial Growth Factor (VEGF). The effects of these factors appear to be
      twofold: To inhibit effector function and to impair the development of immune
      cells by acting on earlier stages of immunopoiesis. Immune suppression by tumors
      is accomplished by a variety of cellular and molecular mechanisms, and virtually
      all branches of the immune system can be affected. VEGF and its receptors have
      profound effects on the early development and differentiation of both vascular
      endothelial and hematopoetic progenitors (9). It induces proliferation of mature
      endothelial cells and is an important component in the formation of tumor
      neovasculature (10). VEGF is abundantly expressed by a large percentage of solid
      tumors and this over-expression is closely associated with a poor prognosis
      (11,12). Some of the earliest hematopoetic progenitors express receptors for VEGF
      (13), and we have demonstrated that VEGF causes a defect in the functional
      maturation of dendritic cells (DC) from progenitors. This developmental defect is
      associated with impaired activation of NF-kappaB (14-17). This review describes
      research demonstrating that VEGF is not only important for tumor vascularization,
      but is also a key factor produced by solid tumors to inhibit recognition and
      destruction of tumor cells by the immune system.

PMID- 11444392
TI  - Neuroendocrine-immune system interactions in amphibians: implications for
      understanding global amphibian declines.
AB  - Amphibians are ancient creatures valued by biologists and naturalists around the
      world. They share with all other vertebrates a complex neuroendocrine system that
      enables them to flourish in a variety of aquatic and semiaquatic environments.
      Studies from a number of laboratories have demonstrated that the immune system of
      amphibian species is nearly as complex as that of mammals. Yet for reasons that
      are not well understood, amphibian species are facing greater survival challenges
      than in the recent past. This article will review our current understanding of
      the neuroendocrine immune system interactions in amphibians and address the
      question of whether environmental stressors may contribute to immunosuppression
      and amphibian declines.

PMID- 11444393
TI  - Effects of androgens on T and B lymphocyte development.
AB  - The sexually dimorphic nature of normal immune responses and the remarkably
      higher incidence of autoimmune diseases in females have suggested a role for
      gonadal steroid hormones as modulators of immune system function. We have
      investigated the effects of androgens on the development of lymphocytes in the
      thymus and bone marrow. Expression of the androgen receptor, the ligand-activated
      transcription factor that mediates hormone actions, has been documented in
      lymphoid and nonlymphoid cells of thymus and bone marrow, but not in mature
      peripheral lymphocytes. This expression pattern suggests that the major impact of
      androgens must be on the developmental maturation of T and B lymphocytes rather
      than on the mature effector cells. Recent experiments have explored whether
      developing lymphoid precursors are the direct targets of androgen action or
      whether supporting cells, such as thymic epithelial cells and bone marrow stromal
      cells, are required for the receptor-mediated effects of androgens on lymphoid
      cell development. Bone marrow transplantation techniques using an androgen
      resistant mouse strain permit the creation of chimeric mice with androgen
      receptor-defective lymphoid or epithelial/stromal cellular compartments. Hormonal
      manipulation experiments in these chimeric animals have suggested that thymic
      epithelial cells and bone marrow stromal cells are mediators of androgenic
      effects on immature lymphocytes. The long-range goal of these studies is to
      understand the basis for the disproportionate occurrence of autoimmune diseases
      in females.

PMID- 11444394
TI  - Functional genomics of the murine immune system.
AB  - The mouse and human genome sequences provide new opportunities to characterize
      mammalian gene functions on a genome-wide level. Toward this end, we have
      developed strategies for tagged-sequence mutagenesis in mice. Tagged-sequence
      mutagenesis has been used first, to analyze genes implicated in
      posttranscriptional gene regulation, and second, to identify genes important in
      immune cell development and function.

PMID- 11444395
TI  - Immunology at Vanderbilt University.

PMID- 11444396
TI  - Innate immunity and inflammation: a transcriptional paradigm.
AB  - The innate immune response and the process of inflammation are interwoven.
      Excessive and continuing cytokine production in response to bacterial
      lipopolysacharides (LPS) or superantigens is a hallmark of the systemic
      inflammatory response (IR), which can be life-threatening. Dissemination of these
      bacterial products induces waves of proinflammatory cytokines that cause vascular
      injury and multiple organ dysfunction. Both LPS and superantigens induce
      signaling to the nucleus in mononuclear phagocytes and T cells, respectively.
      These signaling pathways are mediated by NF-kappaB and other stress-responsive
      transcription factors (SRTFs), which play a critical role in reprogramming gene
      expression. The nuclear import of NF-kappaB allows transcriptional activation of
      over 100 genes that encode mediators of inflammatory and immune responses. We
      have developed a novel method to block nuclear import of NF-kappaB through cell
      permeable peptide transduction in monocytes, macrophages, T lymphocytes, and
      endothelial cells. Strikingly, a cell-permeable peptide that antagonizes nuclear
      import of NF-kappaB and other SRTFs, suppressed the systemic production of
      proinflammatory cytokines (TNFalpha and interferon gamma) in mice challenged with
      a lethal dose of LPS, and increased their survival by at least 90%. Thus,
      systemic inflammatory responses are critically dependent on the transcriptional
      activation ofcytokine genes that are controlled by NF-kappaB and other SRTFs.

PMID- 11444397
TI  - Brain tumor resection in the awake patient.

PMID- 11444398
TI  - How physician gender shapes the communication and evaluation of medical care.

PMID- 11444399
TI  - Awake craniotomy for aggressive resection of primary gliomas located in eloquent
      brain.
AB  - OBJECTIVE: To determine with intraoperative neurologic and language examinations
      the maximal tumor resection achievable with acceptable postoperative neurologic
      dysfunction in patients undergoing awake stereotactic glial tumor resection in
      eloquent regions of the brain. PATIENTS AND METHODS: Between October 1995 and
      December 2000, 65 patients underwent frameless stereotactic resection of glial
      tumors located in functioning tissue. During the resection, continuous
      examinations by a neurologist and speech pathologist were performed. The goal of
      surgery was to resect the maximum neurologically permissible tumor volume defined
      on preoperative T2 imaging. Tumor resection was stopped at the onset of
      neurologic dysfunction. Novel segmentation software was used to measure tumor
      cytoreduction based on pre- and postoperative magnetic resonance imaging. All
      patients underwent 3-month postoperative neurologic examinations to determine
      functional outcomes. RESULTS: The cortical and subcortical white matter tracts at
      risk for injury were the left frontal operculum in 15 patients, the central
      lobule in 38, the insula in 11, and the left angular gyrus in 1. Thirty-four
      (52%) had a greater than 90% reduction in T2 signal postoperatively. In 26
      patients thought to have low-grade tumors based on preoperative imaging, 12
      proved to have grade 3 gliomas. Forty-eight patients (74%) developed
      intraoperative deficits; 34 (71%) recovered to a modified Rankin grade of 0 or 1
      at 3 months postoperatively, 11 (23%) achieved a modified Rankin grade of 2, and
      3 patients (6%) achieved a modified Rankin grade of 3 or 4 at 3-month follow-up.
      There was no operative mortality; 17 patients (26%) died from tumor progression
      during the follow-up period. CONCLUSIONS: Combining frameless computer-guided
      stereotaxis with cortical stimulation and repetitive neurologic and language
      assessments facilitates tumor resection in functioning brain regions. Resecting
      tumor until the onset of neurologic deficits allows for a good functional
      recovery. Imaging software can objectively and accurately measure preoperative
      and postoperative tumor volumes.

PMID- 11444400
TI  - Prevalence of use of herbal products by adults in the Minneapolis/St Paul, Minn,
      metropolitan area.
AB  - OBJECTIVES: To document the prevalence of use of herbal products among adults in
      a large metropolitan area and to examine issues surrounding such use. SUBJECTS
      AND METHODS: Of people aged 18 years and older residing in the Minneapolis/St
      Paul, Minn, metropolitan area, 752 were randomly selected from Minnesota
      Department of Public Safety Driver and Vehicle Service Division data tapes.
      Between June and August 1999, surveys were mailed to determine use of any herb
      and use of 13 specific herbs. Rationale for use, perceived efficacy, and source
      of product information were assessed for each of the specific herbs. RESULTS: Of
      the initial 752 persons, 580 were eligible, and 376 returned a completed survey,
      resulting in a response rate of 65%. When asked whether they had used an herb
      during the past 12 months, 230 respondents (61.2%) reported that they had.
      Prevalence of use of specific herbs ranged from 30.9% for ginseng to 3.0% for
      milk thistle. The most commonly reported reasons for using herbs varied by the
      type of herb, although for 5 of the herbs, the most frequently mentioned reason
      was to promote general health/well-being. For 11 of the 13 herbs, less than 60%
      of those who used the herb rated it as effective or very effective. Family,
      friends, and written materials were the leading sources of product information
      among those taking 9 of the 13 specific herbs. CONCLUSIONS: Herbs are used
      frequently to treat or prevent an array of health conditions. At present, people
      who use herbal products appear to rely predominantly on family and friends for
      information.

PMID- 11444401
TI  - Symptom-triggered therapy for alcohol withdrawal syndrome in medical inpatients.
AB  - OBJECTIVE: To assess the efficacy of symptom-triggered therapy vs usual care for
      alcohol withdrawal syndrome (AWS) in medical inpatients. PATIENTS AND METHODS:
      This study was a retrospective analysis of patients admitted to general medical
      services between January 1, 1995, and December 31, 1998, who experienced AWS
      during the admission. This study was conducted at Saint Marys Hospital,
      Rochester, Minn. Patients were identified from hospital discharge diagnoses and
      pharmacy data. Symptom-triggered therapy for AWS was initiated in 1997. Patients
      were divided into preimplementation (1995-1996) and postimplementation (1997
      1998) cohorts. Age, sex, medical comorbid conditions, previous AWS (including
      seizures and delirium tremens), duration of treatment for AWS, benzodiazepine use
      and dose, complications of AWS, and adverse outcomes of treatment during the
      incident admission were abstracted from the medical records of eligible patients.
      Comorbid conditions were classified according to the Charlson comorbidity index.
      Differences between the cohorts were assessed with use of logistic regression
      models and analysis of covariance. RESULTS: Review of medical records from 638
      admissions (536 patients) yielded 216 admissions eligible for this study. After
      adjustment for age, sex, Charlson comorbidity index, previous AWS, previous
      alcohol withdrawal seizures, and previous delirium tremens, we found no
      significant difference between cohorts for duration of treatment (P=.16),
      benzodiazepine use (P=.21), total dose of benzodiazepine (P=.38), or total
      complication rate (P=.053). We did observe a significant difference in the
      occurrence of delirium tremens between the 2 treatment groups (P=.04). This was
      especially apparent for patients with no history of delirium tremens.
      CONCLUSIONS: Symptom-triggered therapy is effective treatment for AWS in medical
      inpatients. In this retrospective study, it did not result in shorter duration of
      treatment but was associated with a decreased occurrence of delirium tremens, the
      most severe and life-threatening complication of AWS. This result was most
      apparent in patients with no history of delirium tremens.

PMID- 11444402
TI  - Lymph node-positive prostate cancer: evaluation of the results of the combination
      of androgen deprivation therapy and radiation therapy.
AB  - OBJECTIVE: To evaluate the outcome of patients with pathologic stage IV prostate
      cancer treated with androgen ablation plus external-beam radiation therapy.
      PATIENTS AND METHODS: Sixty consecutive patients treated between August 1986 and
      February 1995 with androgen ablation plus radiation therapy for stage IV (T1-4 N1
      M0) adenocarcinoma of the prostate were selected for outcome analysis in this
      retrospective study. Bilateral pelvic lymphadenectomy was performed in 56
      patients (93%). The 4 remaining patients had pelvic adenopathy on computed
      tomography, which was confirmed histologically in all patients. The median
      pretreatment prostate-specific antigen (PSA) level was 28.8 ng/mL (mean, 55 ng/
      mL; range, 0.1-428 ng/mL). All patients received radiation therapy to the
      prostate, and 29 (48%) had pelvic node radiation. Biochemical failure was defined
      according to the American Society for Therapeutic Radiology and Oncology criteria
      of 3 successive increases in the PSA level. RESULTS: The median follow-up
      duration for surviving patients was 101.1 months (range, 20-134 months).
      Biochemical failure with (in 2 patients) or without (in 10 patients) clinically
      evident disease relapse was noted in 12 patients (20%). Four additional patients
      (7%) had clinical relapse without biochemical failure. Local recurrences were
      observed in 6 patients (10%), and this clinical impression was confirmed by
      biopsy in 4 patients. Thirteen patients (22%) died of causes related to prostate
      cancer. The biochemical relapse-free, clinical disease-free, overall, and cause
      specific survival rates at 5 years were 82%, 84%, 76%, and 80%, respectively.
      CONCLUSIONS: This observational case series of patients treated with the
      combination of external-beam radiation therapy and permanent androgen ablation
      for pathologic stage IV prostate cancer suggests that the addition of androgen
      deprivation therapy to radiation therapy may improve disease outcome. In the
      absence of randomized trial results, these observations may be beneficial in
      clinical decision making.

PMID- 11444403
TI  - Predictors of macrovascular disease in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To assess the importance of classic and nonclassic risk factors in the
      development of coronary artery disease (CAD) or cerebrovascular disease (CVD) in
      patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS: In this
      community-based, prospective cohort study, quantitative measurements for
      cholesterol, triglycerides (TGs), glucose, and lipoprotein(a) detected as a
      sinking pre-beta-lipoprotein band on electrophoresis were obtained from 1968
      through 1982 from 449 patients who were free of CAD and CVD but had type 2 DM.
      Demographic data and covariables obtained were age, body mass index, duration of
      diabetes, sex, smoking, and hypertension. The relationship of individual
      continuous factors to the development of CAD and CVD as well as multivariate
      models were evaluated with use of the Cox proportional hazards model. The primary
      outcome was to determine which risk factors are associated with development of
      CAD or CVD in patients with type 2 DM. RESULTS: After a mean follow-up of 13
      years, 216 CAD and 115 CVD events had developed. The hazard ratio estimates with
      95% confidence intervals (CIs) for CAD after multivariate analysis were
      significant for age, 1.45 (95% CI, 1.27-1.67); fasting glucose levels at
      enrollment, 1.63 (95% CI, 1.17-2.25); smoking, 1.45 (95% CI, 1.10-1.91); and TGs,
      1.49 (95% CI, 1.15-1.92). The hazard ratio estimates for CVD were significant for
      age, 1.95 (95% CI, 1.59-2.38); hypertension, 1.89 (95% CI, 1.30-2.74); fasting
      glucose levels at enrollment, 1.69 (95% CI, 1.06-2.70); and smoking, 1.57 (95%
      CI, 1.07-2.30). CONCLUSION: In diabetic patients, age, fasting glucose levels,
      smoking, and TG levels are independent risk factors for development of CAD
      events. Age, hypertension, glucose, and smoking predicted development of CVD
      events.

PMID- 11444404
TI  - Prevention of Lyme disease: a review of the evidence.
AB  - The Healthy People 2010 public health goals targeted a 44% decrease in the
      incidence of Lyme disease, the most commonly reported tick-borne illness in the
      United States. To review Lyme disease prevention, clinical trials,
      epidemiological and experimental studies, and predictive models were evaluated.
      Geographic distribution of ixodid vectors and local landscape predict Lyme
      disease risk. Density of infected ticks correlates with incidence and prevalence
      of Lyme disease, but risk quantitation is made uncertain by tick aggregation and
      inability to predict tick-human interactions. Outdoor activities are
      inconsistently or weakly associated with risk, and most infections likely occur
      in residential areas during routine activities. Tick control (burning or removing
      vegetation, acaricide use, and deer elimination) reduces Ixodes scapularis
      populations by up to 94%, and acaricide application to wildlife decreases nymphal
      I scapularis populations by up to 83%. The effect of these strategies on
      incidence of Lyme disease in humans is unknown. Studies show that only 40% to 50%
      of adults take precautions against tick bites even when they are aware of Lyme
      disease. Effective protection afforded by personal precautions (wearing
      protective clothing, avoiding ticks, and using insect repellant) has not been
      shown prospectively. Antimicrobial prophylaxis of tick bites is not warranted.
      Clinical trials showed vaccines containing recombinant OspA of Borrelia
      burgdorferi to be efficacious and well tolerated. Currently, vaccination is the
      only empirically demonstrated method to prevent Lyme disease. The best evidence
      supports prevention efforts focused on practices that encourage immunization,
      Lyme disease awareness, and possibly treatment of deer.

PMID- 11444405
TI  - Clostridium difficile-associated diarrhea and colitis.
AB  - Clostridium difficile is a spore-forming toxigenic bacterium that causes diarrhea
      and colitis, typically after the use of broad-spectrum antibiotics. The clinical
      presentation ranges from self-limited diarrhea to fulminant colitis and toxic
      megacolon. The incidence of this disease is increasing, resulting in major
      medical and economic consequences. Although most cases respond quickly to medical
      treatment, C difficile colitis may be serious, especially if diagnosis and
      treatment are delayed. Recurrent disease represents a particularly challenging
      problem. Prevention is best accomplished by limiting the use of broad-spectrum
      antibiotics and following good hygienic techniques and universal precautions to
      limit the transmission of bacteria. A high index of suspicion results in early
      diagnosis and treatment and potentially reduces the incidence of complications.

PMID- 11444406
TI  - Endoscopic palliation of malignant dysphagia.
AB  - Esophageal cancer is the primary cause of malignant dysphagia, a major cause of
      morbidity and mortality. In patients with esophageal cancer that is unresectable
      at the time of diagnosis, palliation is the major goal. Surgical treatment as
      well as radiation and chemoradiation therapy are traditional approaches for such
      patients. Endoscopic therapy is useful for patients with poor performance status,
      those in whom other treatments have failed, and those with tracheoesophageal
      fistulas. In recent years, self-expanding metal stents have become an important
      new endoscopic treatment modality for palliation of malignant dysphagia in a wide
      range of patients. Appropriate patient selection is paramount when a mode of
      palliation for malignant dysphagia is being selected. Although various treatment
      options exist for palliation of malignant dysphagia, comparative studies among
      these modalities are needed.

PMID- 11444407
TI  - Treating depression with selective serotonin reuptake inhibitors: a practical
      approach.
AB  - Depression is a common disorder that is becoming better understood as an illness
      that can be chronic, recurrent, and refractory to treatment. Depression can
      produce substantial suffering and profoundly affect a patient's self-esteem,
      relationships, and functional capacity. The improved adverse-effect profile and
      safety from overdose of selective serotonin reuptake inhibitors (SSRIs) have led
      to treatment of milder forms of depression and thus increased treatment of
      depression overall. This article synthesizes several previously published reviews
      and psychopharmacology resources and addresses practical issues related to
      initiating, monitoring, continuing, and discontinuing SSRIs. Precautions related
      to SSRI use and important considerations for various types of depression are
      discussed.

PMID- 11444408
TI  - 73-year-old woman with painful lower extremity ulcers.

PMID- 11444409
TI  - Calciphylaxis associated with cholangiocarcinoma treated with low-molecular
      weight heparin and vitamin K.
AB  - Calciphylaxis is a rare disorder of small-vessel calcification and cutaneous
      infarction associated with chronic renal failure. Rare cases of calciphylaxis not
      associated with chronic renal failure have been reported with breast cancer,
      hyperparathyroidism, and alcoholic cirrhosis. To our knowledge, we report the
      first case of calciphylaxis without chronic renal failure associated with
      cholangiocarcinoma and the first attempt to treat calciphylaxis with vitamin K. A
      56-year-old woman presented with necrotic leg ulceration. She was treated
      initially with low-molecular-weight heparin, with no effect. A coagulation work
      up showed vitamin K deficiency. During vitamin K therapy, the patient had
      fulminant progression of the calciphylaxis. She died, and an autopsy showed
      metastatic cholangiocarcinoma. Thrombosis and protein C deficiency have been
      implicated in the pathophysiology of calciphylaxis. Functional protein C
      deficiency may be one of several factors contributing to the development of
      calciphylaxis. Vitamin K therapy was ineffective in our patient and may have been
      detrimental.

PMID- 11444410
TI  - Calcium embolism of the coronary arteries after percutaneous mitral balloon
      valvuloplasty.
AB  - Two cases of rare, catastrophic calcium emboli to the coronary arteries
      immediately after percutaneous mitral balloon valvuloplasty are presented.
      Preoperative echocardiographic findings may identify patients at risk for this
      complication. These cases should increase the awareness of calcium emboli and
      lead to consideration of urgent coronary angiography for patients with signs or
      symptoms of acute coronary occlusion after valvuloplasty.

PMID- 11444411
TI  - Chronic renal failure secondary to oxalate nephropathy: a preventable
      complication after jejunoileal bypass.
AB  - Enteric hyperoxaluria is a commonly seen adverse event after the jejunoileal
      bypass procedure. The increased concentration of urinary oxalate predisposes
      bypass patients to various renal complications such as nephrolithiasis and
      oxalate nephropathy. If not diagnosed and appropriately treated, these
      complications can lead to irreversible renal damage. We describe 3 patients in
      whom severe renal complications developed with irreversible compromise of renal
      function after a jejunoileal bypass. Patients who undergo a jejunoileal bypass
      require lifelong follow-up with close monitoring of their renal function. Marked
      decline in renal function mandates prompt investigation and aggressive
      intervention, including reversal of the jejunoileal bypass if necessary. Chronic
      renal failure secondary to oxalate nephropathy is preventable and treatable but
      may require conversion of a jejunoileal bypass to a more current form of bypass.

PMID- 11444412
TI  - Work-related factors and mortality -- what is the burden?

PMID- 11444413
TI  - Epidemiologic estimate of the proportion of fatalities related to occupational
      factors in Finland.
AB  - OBJECTIVES: This study attempts to estimate the proportion of annual deaths
      related to occupational factors in Finland and considers related methodological
      issues and associated uncertainties. METHODS: Statistics on causes of death,
      numbers of subjects exposed, and risk ratios obtained from the epidemiologic
      literature were used to estimate the population attributable fraction and disease
      burden for causes of death from work-related diseases. Gender-, age- and disease
      specific numbers of deaths were provided by Statistics Finland for 1996.
      Information on the size of the population, broken down by gender, age,
      occupation, and industry, was acquired from population censuses. A Finnish job
      exposure matrix supplied data on the prevalence of exposure for specific agents
      and the level of exposure among exposed workers. RESULTS: The attributable
      fraction of work-related mortality in the relevant disease and age categories was
      estimated to be 7% (10% for men and 2% for women), and for all diseases and ages
      the fraction was 4%. For the main cause-of-death categories, the attributable
      fraction became 12% for circulatory system diseases, 8% for malignant neoplasms,
      4% for respiratory system diseases, 4% for mental disorders, 3% for nervous
      system diseases, and 3% for accidents and violence. The following estimates were
      obtained for specific important diseases: 24% for lung cancer, 17% for ischemic
      heart disease, 12% for chronic obstructive pulmonary disease, and 11% for stroke.
      Based on these fractions, the total number of work-related deaths that occurred
      in Finland in 1996 was calculated to be on the order of 1800 (employed work force
      of 2.1 million); 86% involved men. CONCLUSIONS: High-quality epidemiologic
      studies and national survey data are essential for obtaining reliable estimates
      of the proportion of deaths attributable to occupational factors. The magnitude
      of work-related mortality is an insufficiently recognized contributor to total
      mortality in Finland, especially from circulatory diseases and other diseases
      caused by exposure to agents other than asbestos.

PMID- 11444414
TI  - Mortality attributable to work.

PMID- 11444415
TI  - A comparison of intakes of breast-fed and bottle-fed infants during the first two
      days of life.
AB  - OBJECTIVE: In the first days of life, breast-fed infants consume minimal amounts
      of milk; this may be explained by substrate limitation (limited milk output)
      and/or by self-limitation (through low appetite and/or suck-swallow competency).
      The spontaneous milk intake of unrestricted formula-fed infants has not been
      studied to date. We compared the spontaneous formula intake of unrestricted
      formula-fed infants to that of breast-fed infants over the first 48 hours of
      life. We hypothesized that 1) spontaneous formula intake of unrestricted infants
      is much higher than that of breast-fed infants and 2) spontaneous formula intake
      correlates positively with gestational age or birthweight. METHODS: We studied 43
      healthy, term infants. By maternal choice, 15 infants were exclusively breast-fed
      and 28 were formula-fed ad libitum every four hours. Breast-fed infants were
      weighed before and one hour after initiation of feeding, and intake was
      calculated from the difference between the measurements and corrected
      individually for the infant's normal postnatal decrease in body weight. Bottles
      offered to formula-fed infants contained 60 cc, and the remainder was carefully
      measured. Intakes were expressed as cc/kg/d, and weight changes as % of
      birthweight. Statistical methods included Student's t tests and stepwise
      regression analysis. RESULTS: Breast feeding on Day I was 9.6 +/- 10.3 (mean +/-
      SD) vs. 18.5 +/- 9.6 cc/kg/d in formula-fed infants (p=0.011); on Day 2 it was
      13.0 +/- 11.3 vs. 42.2 +/- 14.2 cc/kg/d (p<0.001). Breast-fed infants lost
      significantly more weight on Day 2 (p=0.015). In multiple regression, when the
      dependent variable was the second-day intake, the significant independent
      variables were group (higher intake in the formula-fed group), weight loss (the
      higher the weight loss, the lower the intake), and first-day intake (the higher
      the first-day intake, the higher the second-day intake). CONCLUSION: Newborn
      infants offered formula ad libitum every four hours consumed much larger amounts
      than breast-fed infants fed according to the same schedule. In addition, weight
      loss was more marked in breast-fed infants on Day 2 of life.

PMID- 11444416
TI  - Potential antioxidant effects of zinc and chromium supplementation in people with
      type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the effects of combined zinc (Zn) and chromium (Cr)
      supplementation on oxidative stress and glucose homeostasis of people with type 2
      diabetes. DESIGN: Tunisian adult subjects with HbA1C > 7.5% were supplemented for
      6 months with 30 mg/d of Zn as Zn gluconate or 400 microg/d of Cr as Cr pidolate
      or combined Zn/Cr supplementation or placebo. The effects of supplementation on
      plasma zinc (Zn), copper (Cu), selenium (Se), urinary Zn, Cr, plasma
      thiobarbituric acid reactive substances (TBARS), Cu-Zn superoxide dismutase (SOD)
      and Se glutathione peroxidase (GPx) in red blood cells, blood lipids and
      lipoproteins, HbA1C and fasting glucose were measured at the beginning of the
      study and after six months. RESULTS: At the beginning of the study, more than 30%
      of the subjects may have been Zn deficient with plasma Zn values less than 10.7
      mircomol/L, whereas levels of plasma Cu, Se and antioxidant RBC enzyme activities
      were in the normal ranges. Following supplementation, there were significant
      decreases of plasma TBARS in the Cr (13.6%), Zn (13.6%) and Zn/Cr (18.2%) groups
      with no significant changes in the placebo group. The value for the TBARS of the
      control healthy Tunisian subjects was 2.08 +/- 0.04 micromol/L and that of the
      Tunisian subjects with diabetes was 3.32 +/- 0.05 micromol/L. This difference of
      1.24 micromol/L between the control group and the subjects with diabetes was
      reduced from 36% to 50% in the three supplemented groups. Supplementation did not
      modify significantly HbAIC nor glucose homeostasis. No adverse effects of Zn
      supplementation were observed on Cu status. HDL cholesterol nor interactions in
      Zn or Cr. CONCLUSIONS: These data suggest the potential beneficial antioxidant
      effects of the individual and combined supplementation of Zn and Cr in people
      with type 2 DM. These results are particularly important in light of the
      deleterious consequences of oxidative stress in people with diabetes.

PMID- 11444417
TI  - Calcium intake and bone mass development among Israeli adolescent girls.
AB  - OBJECTIVE: To determine the possible relationship between food and life style
      habits and bone health in adolescent Israeli females. METHODS: 2,000 adolescent
      Israeli Jewish and Arab high-school girls (mean age 14.5) completed a semi
      quantitative food frequency questionnaire and a personal history questionnaire.
      27 food components were calculated for each subject. Bone mineral content and
      density were determined for 112 subjects with calcium intake below 800 mg/day.
      RESULTS: Average calcium intake was found to be 1,260 mg/day, but 20% of all
      girls had a calcium intake below 800 mg/day. All low-energy diets were very low
      in calcium, as mean calcium intake per 1,000 calories was 411 128 grams. A large
      percentage of diets with less than 800 mg calcium were also deficient in
      phosphorus (95.2%), magnesium (84.8%). iron (90.5%) and zinc (100%). Due to
      differences in food sources. Jewish girls had more phosphorus in their diet, but
      less magnesium and iron compared to Arab girls. Calcium and zinc deficiencies in
      Jewish and Arab diets were similar. A negative correlation was found between body
      mass index (BMI) and age at menarche for all girls in the study. Bone mineral
      density (BMD) measured for girls with calcium intake below 800 mg/day distributed
      normally around the average when compared to age matched controls despite their
      low calcium intake. There was a strong positive correlation between BMD and bone
      mineral content (BMC) at all sites and body weights. CONCLUSIONS: Low calcium
      intake, other nutritional deficiencies and delayed menarche due to low-energy
      diet in the growing period and in adolescence may prevent the formation of
      healthy bones. There is no evidence of lower bone mass among the low calcium
      intake group in the study population at this stage. It remains to be documented
      if the window of opportunity for optimal bone accretion for this group will be
      missed in the future. possibly leading to increased risk of osteoporosis.

PMID- 11444418
TI  - Hypocholesterolemic effect of an enteric-coated garlic supplement.
AB  - OBJECTIVE: To evaluate the hypocholesterolemic effect of an enteric-coated garlic
      supplement standardized for allicin-releasing potential in mild to moderate
      hypercholesterolemic patients. METHODS: A double-blind randomized, placebo
      controlled intervention study was conducted in 46 hypercholesterolemic subjects
      who had failed or were not compliant with drug therapy. Each subject was given
      dietary counseling to lower fat intake and enteric-coated Australian garlic
      powder tablets with 9.6 mg allicin-releasing potential or matching placebo
      tablets. RESULTS: After 12 weeks, the garlic supplement group (n=22) had a
      significant reduction in total cholesterol (TC, -0.36 mmol/L. -4.2%) and LDL
      cholesterol (LDL-C, -0.44 mmol/L, -6.6%) while the placebo group (n=24) had a non
      significant increase in TC (0.13 mmol/L, 2.0%) and LDL-C (0.18 mmol/L, 3.7%). HDL
      cholesterol was significantly increased in the placebo group (0.09 mmol/L, 9.1%),
      compared to the garlic group (-0.02 mmol/L, -0.9%). and no significant difference
      in triglycerides or in LDL/HDL ratio was observed between groups. CONCLUSIONS:
      The study demonstrates that enteric-coated garlic powder supplements with 9.6 mg
      allicin-releasing potential may have value in mild to moderate
      hypercholesterolemic patients when combined with a low fat diet. Taken with other
      evidence, the efficacy of garlic for lipoprotein metabolism might require allicin
      bioavailability to be enhanced through the use of, for example, an enteric-coated
      dose form. If this is the case, the possibility remains that greater
      hypocholesterolemic efficacy may be evident at a higher allicin dose. Also
      noteworthy in this study was a small reduction in energy intake with garlic
      compared with placebo, attributable to reduction in fat, carbohydrate and alcohol
      intakes. This may also have contributed to the effects on blood lipids. This
      study suggests that garlic supplementation has a cholesterol-lowering effect,
      which may be mediated by direct action of a biologically active compound or
      compounds and in part through the effect on food and nutrient intake.

PMID- 11444419
TI  - No significant effects of lutein, lycopene or beta-carotene supplementation on
      biological markers of oxidative stress and LDL oxidizability in healthy adult
      subjects.
AB  - OBJECTIVE: The objective of this study was to determine the effect of individual
      carotenoid supplementation on biochemical indices of oxidative status in
      apparently healthy adult males. METHODS: The study was a placebo controlled
      single blind study. Healthy male volunteers (n= 175) were assigned to four
      groups. They received daily supplements of beta-carotene (15 mg), lutein (15 mg),
      lycopene (15 mg) and placebo for three months. The effects of the supplementation
      on antioxidant status were monitored by plasma carotenoid, vitamin C and A
      levels, glutathione (GSH and GSSG) concentrations, protein SH groups. erythrocyte
      antioxidant enzyme activities (Cu-Zn SOD, Se-GSH-Px) and susceptibility of LDL to
      copper-induced oxidation. RESULTS: beta-carotene, lycopene and lutein
      supplementation led to significant plasma and LDL increases in each of these
      carotenoids, without modifications of other carotenoid levels in plasma or in
      LDL. The supplementation failed to enhance the resistance of LDL to oxidation or
      to modify the LDL polyunsaturated/ saturated fatty acid ratio. Vitamin C, GSH,
      protein SH groups and antioxidant metalloenzyme activities were also unchanged.
      CONCLUSION: We did not observe beneficial or adverse effects of lutein, lycopene
      or beta-carotene supplementation on biomarkers of oxidative stress. In apparently
      healthy subjects, carotenoid supplementation does not lead to significantly
      measurable improvement in antioxidant defenses.

PMID- 11444420
TI  - Absorbability and cost effectiveness in calcium supplementation.
AB  - BACKGROUND: Cost-effectiveness of calcium supplementation depends not only on the
      cost of the product but on the efficiency of its absorption. Published cost
      benefit analyses assume equal bioavailability for all calcium sources. Some
      published studies have suggested that there are differences in both the
      bioavailability and cost of the major calcium supplements. DESIGN: Randomized
      four period, three-way cross-over comparing single doses of off-the-shelf
      commercial calcium supplements containing either calcium carbonate or calcium
      citrate compared with a no-load blank and with encapsulated calcium carbonate
      devoid of other ingredients; subjects rendered fully vitamin D-replete with 10
      microg/day 25(OH)D by mouth, starting one week prior to the first test. SUBJECTS:
      24 postmenopausal women METHODS: Pharmacokinetic analysis of the increment in
      serum total and ionized calcium and the decrement in serum iPTH induced by an
      oral calcium load, based upon multiple blood samples over a 24-hour period;
      measurement of the rise in urine calcium excretion. Data analyzed by repeated
      measures ANOVA. Cost calculations based on average retail prices of marketed
      products used in this study from April through October, 2000. RESULTS: All three
      calcium sources (marketed calcium carbonate, encapsulated calcium carbonate and
      marketed calcium citrate) produced identical 24-hour time courses for the
      increment in total serum calcium. Thus, these were equally absorbed and had
      equivalent bioavailability. Urine calcium rose slightly more with the citrate
      than with the carbonate preparations. but the difference was not significant.
      Serum iPTH showed the expected depression accompanying the rise in serum calcium,
      and there were no significant differences between products. CONCLUSION: Given the
      equivalent bioavailability of the two marketed products, the cost benefit
      analysis favors the less expensive carbonate product.

PMID- 11444421
TI  - Iron and folate in fortified cereals.
AB  - BACKGROUND: Fortification of cereal-grain products was introduced in 1941 when
      iron and three vitamins were added to flour and bread. Ready-to-eat cereals were
      fortified at about the same time. These fortifications have contributed to
      increased dietary iron intake and reductions in iron deficiency anemia in the US.
      In 1996, FDA finalized rules for fortification of specific enriched cereal-grain
      products with folic acid. This measure was instituted to increase the folate
      intakes of women of child-bearing age and thereby reduce the risk of having a
      pregnancy affected with a neural tube birth defect. However, with recent
      increases in fortification, public health officials in the US are concemed that
      excess intake of specific nutrients such as iron and folic acid may result in
      toxic manifestations. OBJECTIVE: Our objective was to measure iron and total
      folate content in breakfast cereals and compare assay to label values for % Daily
      Value. We also determined by weight the amount of a ready-to-eat breakfast cereal
      adults would eat and compared this to the labeled serving size, for which the
      reference amount for this cereal per eating occasion was 1 cup or 30 g. DESIGN:
      Twenty-nine breakfast cereals were analyzed for iron content using the
      bathophenanthroline reaction. Twenty-eight cereals were analyzed for total
      folate, utilizing a microbiological assay with tri-enzyme digestion. Serving size
      quantities were estimated in seventy-two adults who regularly ate breakfast
      cereal and were asked to fill a 16 or 22 cm round bowl with the amount of cereal
      that they would consume for breakfast. RESULTS: When the labeled value was
      compared to the assayed value for iron content 21 of the 29 breakfast cereals
      were 120% or more of the label value and 8 cereals were 150% or more of the label
      value. Overall, analyzed values for iron ranged from 80% to 190% of label values.
      Analyzed values for folate ranged from 98% to 320% of label values. For 14 of 28
      cereals, analyzed values exceeded label declarations by more than 150%. Bran
      containing cereals contained the highest amounts of folate relative to their
      label declarations. The median analyzed serving size for the breakfast cereal was
      47 g for females, 61 g for males with a combined median of 56 g as compared to
      the label value of 30 g. CONCLUSIONS: Analyzed values of iron and folic acid in
      breakfast cereals were considerably higher than labeled values. For adults, the
      amount of cereal actually consumed was approximately 200% of the labeled serving
      size. When the quantity of cereal consumed is more than the labeled serving size
      and when the levels of iron and folate are higher than declared, the intake of
      both will be significantly greater than the labeled values. It will be important
      to continue monitoring serum ferritin and folate levels in NHANES IV, since daily
      consumption of breakfast cereals may contribute to excessive intakes of iron and
      folate.

PMID- 11444422
TI  - Relation of serum ascorbic acid to mortality among US adults.
AB  - PURPOSE: To examine the relation between serum ascorbic acid (SAA), a marker of
      dietary intake (including supplements), and cause-specific mortality. SUBJECTS
      AND METHODS: We analyzed data from a probability sample of 8,453 Americans age >
      or = 30 years at baseline enrolled in the Second National Health and Nutrition
      Examination Survey (NHANES II), who were followed for mortality endpoints. We
      calculated relative hazard ratios as measures of disease association comparing
      the mortality rates in three biologically relevant SAA categories. RESULTS:
      Participants with normal to high SAA levels had a marginally significant 21% to
      25% decreased risk of fatal cardiovascular disease (CVD) (p for trend = 0.09) and
      a 25% to 29% decreased risk of all-cause mortality (p for trend <0.001) compared
      to participants with low levels. Because we determined that gender modified the
      association between SAA levels and cancer death, we analyzed these associations
      stratified by gender. Among men, normal to high SAA levels were associated with
      an approximately 30% decreased risk of cancer deaths, whereas such SAA levels
      were associated with an approximately two-fold increased risk of cancer deaths
      among women. This association among women persisted even after adjustment for
      baseline prevalent cancer and exclusion for early cancer death or exclusion for
      prevalent cancer. CONCLUSIONS: Low SAA levels were marginally associated with an
      increased risk of fatal CVD and significantly associated with an increased risk
      for all-cause mortality. Low SAA levels were also a risk factor for cancer death
      in men, but unexpectedly were associated with a decreased risk of cancer death in
      women. If the association between low SAA levels and all-cause mortality is
      causal, increasing the consumption of ascorbic acid, and thereby SAA levels,
      could decrease the risk of death among Americans with low ascorbic acid intakes.

PMID- 11444423
TI  - Role of endothelin in diabetic vascular complications.
AB  - Endothelin-1 (ET-1), a 21 amino acid peptide originally purified from conditioned
      medium of cultures of porcine aortic endothelial cells, is recognized as a
      product of many other cells as well. It is now known that there are three
      endothelin genes in the human genome (ET-1, ET-2, and ET-3). ET-1 and ET-2 are
      both strong vasoconstrictors, whereas ET-3 is a potentially weaker
      vasoconstrictor than the other two isoforms. Besides being the most potent
      vasoconstrictor yet known, ET-1 also acts as a mitogen on the vascular smooth
      muscle, and, thus, it may play a role in the development of vascular diseases. It
      is well known that accelerated angiopathy is a major complication in diabetes
      mellitus. As generalized endothelial cell damage is thought to occur in diabetic
      patients, ET-1, being released from the damaged endothelial cells, is able to
      make contact with the underlying vascular smooth muscle cells and thus could be
      one important cause of diabetic angiopathy. This article summarizes the reported
      literature of the role of ET-1 in the development of diabetic complications, with
      particular focus on the possible role of ET-1 in mediating the effects of
      angiotensin-converting enzyme inhibitors.

PMID- 11444425
TI  - Regulation of insulin-stimulated tyrosine phosphorylation of Shc and Shc/Grb2
      association in liver, muscle, and adipose tissue of epinephrine- and
      streptozotocin-treated rats.
AB  - Shc protein phosphorylation has been extensively characterized as the initial
      step that activates a complex mitogenic pathway through its association with
      Grb2. In the present study, we investigated the adrenergic control of insulin
      induced Shc phosphorylation and Shc-Grb2 association, and the modulating effect
      of streptozotocin-induced diabetes mellitus on Shc phosphorylation and Shc/Grb2
      association. Acute treatment with epinephrine, which leads to a normoglycemic
      insulin-resistant state, does not affect insulin-induced Shc tyrosine
      phosphorylation or Shc-Grb2 association in liver, muscle, or fat. By contrast, a
      significant increase in insulin-induced Shc phosphorylation is observed in liver
      and muscle of rats treated with streptozotocin. The association of Shc/Grb2 is
      also increased in both tissues following insulin treatment. These data suggest
      that while epinephrine preserves the insulin-induced phosphorylation of Shc and
      the mitogenic pathway stimulated by Shc-Grb2 association, treatment with
      streptozotocin leads to a tissue-specific increase in the activity of the initial
      step that ultimately results in the activation of the Shc/Grb2 mitogenic pathway.

PMID- 11444424
TI  - Hormonal regulation and implication of cell signaling in calcium transfer by
      placenta.
AB  - During pregnancy, the human placenta transfers about 30 g of calcium (Ca2+) from
      the mother to the fetus. This transfer is mainly done during the third trimester,
      at a rate of 140 mg/(kg x d). It allows adequate growth and development of the
      fetus, since Ca2+ is vital for the mineralization of the fetus's skeleton and
      many cellular functions. Because Ca2+ flows through the placenta against an
      electrochemical gradient, calcemic hormones could also be involved to overcome
      this gradient. Hormones such as calcitonin, parathyroid hormone (PTH), and PTH
      related peptide (PTHrP) have been found in maternal and fetal circulation, and
      they originate from both parties, as well as from the placenta in the case of
      PTHrP. As the placenta possesses most of the G-protein-coupled receptors to bind
      these hormones, it is likely that they play an important role in maternal-fetal
      Ca2+ homeostasis. More studies are needed to assess the importance of these
      hormones in the regulation of Ca2+ management during pregnancy, and to understand
      better the cell-signaling pathways involved. This article addresses the current
      knowledge in this field to guide future investigations on the roles, functions,
      and localizations of the components involved during Ca2+ transfer by
      syncytiotrophoblasts.

PMID- 11444426
TI  - Glycogen accumulation in rat pancreatic islets: in vitro experiments.
AB  - Under conditions of sustained hyperglycemia, glycogen accumulates in pancreatic
      islets, but not so in acinar pancreatic cells. Advantage conceivably could be
      taken from such a situation in the perspective of the noninvasive imaging of the
      endocrine pancreas. The present experiments aim, therefore, at characterizing the
      time course for glycogen accumulation in pancreatic islets cultured at a high
      concentration (30 mM) of D-glucose in the presence of tracer amounts of either D
      [U-14C]glucose or 2-deoxy-2-[18F]fluoro-D-glucose. The 14C-labeled glycogen
      content of the cultured islets increased with time (150 min to 72 h), exceeded
      that found in acinar tumoral cells, and did not decrease over 60 min of
      incubation at 30 mM D-glucose in the absence of D-[U-14C]glucose. Glycogenolysis
      was observed, however, when the concentration of D-glucose was decreased to 2.8
      mM and, in such a case, was further enhanced by forskolin and theophylline. Such
      a glycogenolysis coincided with the generation of 14CO2 from radioactive
      intracellular precursors and alteration of the B-cell secretory response to D
      glucose. The radioactive glycogen content was higher in islets exposed to 2-deoxy
      2-[18F]fluoro-D-glucose than D-[U-14C]glucose. Prior exposure of the islets to
      streptozotocin suppressed the accumulation of glycogen during their subsequent
      culture at high D-glucose concentration. These findings may help to define the
      experimental conditions optimal for the labeling and accumulation of islet
      glycogen in vivo.

PMID- 11444427
TI  - Effect of 1alpha,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 on
      metalloproteinase activity and cell maturation in growth plate cartilage in vivo.
AB  - Recent studies indicate that 1alpha,25-dihydroxyvitamin D3 (1alpha,25[OH]2D3) and
      24R,25-dihydroxyvitamim D3 (24R,25[OH]2D3) differentially regulate proliferation,
      differentiation, and matrix synthesis of growth plate chondrocytes. To determine
      whether both metabolites play the same or different roles in vivo, we used the
      vitamin D-deficient rat as a model. Rickets was induced and then reversed by
      administering a single dose of ergocalciferol, 1alpha,25(OH)2D3, or 24R,25(OH)2D3
      and euthanizing the animals after 4, 24, 48, or 72 h. Growth plates were either
      processed for histology and histomorphometry or extracted with buffered guanidine
      HCl. Neutral metalloproteinase activity in the extracts was measured by use of
      aggrecan-containing beads, and collagenase activity was determined by use of
      radioactive type I collagen. The levels of tissue inhibitor of metalloproteinases
      (TIMP) and plasminogen activator were also determined. The morphology of the
      growth plate varied as a function of treatment. While 24R,25(OH)2D3 appeared to
      affect cell maturation and 1alpha,25(OH)2D3 appeared to affect terminal
      differentiation and calcification, response to ergocalciferol was indicative of
      the combined responses to the individual metabolites. Enzyme activity was
      regulated in a differential manner. Treatment with ergocalciferol produced a
      rapid decline in both neutral metalloproteinase and collagenase activities that
      was statistically significant by 4 h. By contrast, 1alpha,25(OH)2D3 had no effect
      on neutral metalloproteinase activity but caused a significant decrease in both
      active and total collagenase activity by 4 h, while 24R,25(OH)2D3 decreased
      neutral metalloproteinase activity by 48 h and had no effect on collagenase
      activity. Ergocalciferol had no effect on TIMP levels at any time examined,
      whereas 1alpha,25(OH)2D3 caused an increase at 48 and 72 h and 24R,25(OH)2D3
      completely blocked TIMP production at 4 and 24 h. By contrast, plasminogen
      activator activity by ergocalciferol was decreased at 4 h, increased by
      1alpha,25(OH)2D3 at 4 and 24 h, and decreased by 24R,25(OH)2D3 at all time points
      examined. These in vivo results confirm our previous cell culture observations
      showing that growth plate chondrocytes are differentially regulated by
      1alpha,25(OH)2D3 and 24R,25(OH)2D3. Moreover, they show definitively that these
      two vitamin D metabolites play distinct roles not only in regulating neutral
      metalloproteinase and collagenase activities in growth plate cartilage but in
      cell maturation and calcification of this tissue in vivo.

PMID- 11444428
TI  - Gene expression of gonadotropin-releasing hormone and its receptor in rat
      pancreatic cancer cell lines.
AB  - The regression of experimental and clinical pancreatic cancers by treatment with
      gonadotropin-releasing hormone (GnRH) agonists or antagonists has been repeatedly
      reported and is usually presumed to result from the creation of a sex steroid
      deficiency. There are, however, indications that GnRH analogs can also suppress
      the growth of the tumor cells in vitro and that specific binding sites for GnRH
      are present on membranes of these cells. The regulatory role of GnRH in rat
      pancreatic adenocarcinoma was investigated by examining the gene for GnRH and
      GnRH receptor (GnRH-R) in two pancreatic tumor cell lines (AR42J and ARIP).
      Reverse transcriptase polymerase chain reaction and Southern blot analysis
      indicated both GnRH-mRNA and GnRH-R-mRNA transcripts in the two cell lines. This
      is the first report raising the possibility of an autocrine/paracrine role for
      GnRH in rodent malignant pancreas.

PMID- 11444429
TI  - Dopamine D2 receptor gene expression in human adenohypophysial adenomas.
AB  - The inhibitory effects of dopamine on adenohypophysial cells are mediated via
      dopamine subtype 2 receptor (D2R). Dopamine agonists inhibit hormone release and
      induce tumor shrinkage in most prolactin-secreting adenomas, whereas in other
      adenoma types such effects are sporadic. We investigated D2R gene expression by
      in situ hybridization (ISH) and immunocytochemistry in different types of
      pituitary adenomas. By ISH, a variable D2R signal was detected in 79 of 89 cases:
      4 of 6 densely granulated and 8 of 8 sparsely granulated somatotroph, 4 of 4
      mammosomatotroph, 7 of 7 mixed somatotroph-lactotroph, 4 of 4 acidophil stem
      cell, 16 of 16 sparsely granulated lactotroph, 11 of 16 corticotroph (functioning
      and silent), 3 of 4 silent subtype 3, 5 of 5 thyrotroph, 5 of 6 gonadotroph, 5 of
      6 null cell, and 7 of 7 oncocytic adenomas. By immunocytochemistry, D2R protein
      was localized in cytoplasm and nuclei of 60 of 62 adenomas. In lactotroph
      adenomas, long-acting bromocriptine (BEC-LAR) induced a major increase in D2R
      mRNA, which was not accompanied by increased D2R immunoreactivity, suggesting
      mRNA stabilization. In conclusion, D2R gene is expressed in the majority of
      pituitary adenomas representing all tumor types. The significance of nuclear
      localization of D2R protein remains to be clarified.

PMID- 11444430
TI  - Sustained activity of luteal cytosolic phospholipase A2 during luteolysis in
      pseudopregnant rats: its possible implication in tissue involution.
AB  - We investigated the expression and activity of cytosolic phospholipase A2 (cPLA2)
      in the corpus luteum during spontaneous and induced luteolysis in pseudopregnant
      rats. In both models, luteal PLA2 activity rose in association with functional
      regression and persisted during the following structural regression. Tissue
      concentration of prostaglandin F2alpha with a luteolytic potency showed a similar
      fluctuation. The enzyme activity was almost completely suppressed by a cPLA2
      specific inhibitor. Expression of cPLA2, analyzed by immunohistochemistry, became
      enhanced during luteolysis with preferential localization to phagocytotic and
      fibrotic replacement sites. Taken together with our previous finding, the data
      indicate a persistent elevation in luteal cPLA2 expression and activity that may
      affect tissue involution in vivo.

PMID- 11444431
TI  - Effects of cortisol and estradiol on pituitary expression of proopiomelanocortin,
      prohormone convertase-1, prohormone convertase-2, and glucocorticoid receptor
      mRNA in fetal sheep.
AB  - We hypothesized that in the late-gestation sheep fetus there is an interaction
      between the prepartum rise in cortisol and the increase in placental estradiol
      production that allows expression of key components of the fetal hypothalamic
      pituitary-adrenal (HPA) axis. Therefore, the goal of this study was to
      investigate the effects of cortisol on the fetal HPA axis in the presence and
      absence of increased placental estradiol production. We obtained fetal plasma
      samples and pituitary tissue from animals that had received an infusion of either
      cortisol, cortisol and 4-hydroxyandrostenedione (40HA, an aromatase inhibitor),
      saline, or saline + 40HA controls. Cortisol significantly decreased plasma
      adrenocorticotropic hormone concentrations, and in the presence of 40HA reduced
      pituitary proopiomelanocortin (POMC) mRNA levels in the pars distalis. There was
      no effect of any treatment on the expression of the key POMC processing enzymes,
      prohormone convertase-1 or -2 in the fetal pituitary. Conversely, levels of
      glucocorticoid receptor (GR) mRNA in the pituitary were increased with cortisol
      treatment in the absence of increased estradiol. We suggest that in the late
      gestation sheep fetus, cortisol and estradiol have opposite effects on pituitary
      POMC and GR mRNA expression, and interact to regulate these key components of the
      fetal HPA axis.

PMID- 11444432
TI  - Intracerebroventricular insulin-like growth factor-1 decreases feeding in
      diabetic rats.
AB  - Insulin-like growth factor-1 (IGF-1) is a hormone that is important in the
      regulation of growth processes and additionally has been demonstrated to modulate
      metabolic and autonomic responses. Some of its effects are mediated by the
      central nervous system (CNS), and there are IGF-1 receptors dispersed throughout
      the CNS. Both IGF-1 and insulin alter peripheral metabolic and autonomic nervous
      activity by a central mechanism, and the well-defined role of insulin in the
      regulation of feeding, especially in diabetes, led us to investigate the effect
      of chronic central administration of IGF-1 on metabolic and feeding parameters in
      normal and diabetic rats. Normal and diabetic rats with intracerebroventricular
      cannulas were given IGF-1, insulin (0.5 nmol/animal), or artificial cerebrospinal
      fluid via cannula twice daily for 4 d. Blood samples were collected on d 2 and 4,
      and the body weights and food intake were recorded daily. IGF-1 administered
      intracerebroventricularly did not alter plasma glucose, insulin, body weight, or
      food intake in normal rats. However, in diabetic animals, IGF-1 decreased food
      intake but did not alter blood glucose or plasma insulin. In correlated studies,
      intracerebroventricular insulin decreased food intake in both normal and diabetic
      animals. From these studies, we conclude that IGF-1 may act centrally to decrease
      food intake in the hyperphagic diabetic animals but not in normal animals. This
      suggests that diabetic animals have an increased sensitivity to CNS IGF-1.

PMID- 11444433
TI  - Effects of mutating different steroidogenic factor-1 protein regions on gene
      regulation.
AB  - The involvement of cyclic adenosine monophosphate cAMP-dependent protein kinase A
      (PKA) in the regulation of the steroidogenic acute regulatory protein (StAR) and
      the high-density lipoprotein receptor (HDL-R) genes by steroidogenic factor-1 (SF
      1) and cAMP were examined. Cotransfection studies carried out in Kin 8 cells, a
      Y1 cell line (mouse adrenal) with a mutation in the type I PKA regulatory
      subunit, demonstrated that an intact PKA is required for maximal activation and
      that SF-1 participates in cAMP regulation of these genes. Site-directed
      mutational analysis was performed to examine which SF-1 regions could be involved
      in SF-1 transcriptional activation of the StAR and HDL-R genes. SF-1 regions
      protein analyzed were amino acids Thr 60, Ser 203, Ser 431, Thr 462, and the
      activation function-2 domain (amino acids 449-462). Plasmids encoding each of the
      mutated SF-1 proteins were cotransfected with the StAR and HDL-R promoter
      constructs into human bladder carcinoma (HTB-9) cells in the presence or absence
      of dibutyryl cAMP. The results of these studies suggest that although SF-1 is
      required for optimal promoter response to cAMP, transcriptional activation of
      genes by SF-1 and cAMP are promoter dependent, perhaps resulting from gene
      specific interactions of this transcription factor with other regulatory
      proteins.

PMID- 11444434
TI  - Regulation of chicken embryonic growth hormone secretion by corticosterone and
      triiodothyronine: evidence for a negative synergistic response.
AB  - We reported that growth hormone (GH)-secreting cells differentiated by d 16 of
      chick embryonic development and that these somatotrophs were responsive to GH
      releasing hormone and thyrotropin-releasing hormone. The present experiments
      evaluated effects of corticosterone and triiodothyronine (T3) on embryonic GH
      secretion. Anterior pituitary cells from embryonic day (e) 16, e18, and e20 were
      subjected to reverse hemolytic plaque assays (RHPAs) for GH in the absence or
      presence of corticosterone or T3. Corticosterone increased GH secretion from
      embryonic somatotrophs, an effect particularly evident on e16 and e18. T3
      decreased GH secretion on e16, while no effect of T3 was significant on e18 or
      e20. Next, pituitary cells were subjected to RHPAs with T3 and corticosterone
      alone or in combination. Combined treatment with these hormones suppressed GH
      secretion from e16, e18, and e20 somatotrophs to levels below those found under
      basal conditions. We conclude that corticosterone can stimulate GH secretion in
      vitro at all embryonic ages tested. Furthermore, T3 can suppress basal GH
      secretion on e16, and the combination of T3 and corticosterone can suppress GH
      secretion at all ages. These findings indicate that GH secretion during the end
      of chicken embryonic development may be regulated by the interactions of
      endogenous glucocorticoids and thyroid hormones that increase prior to hatching.

PMID- 11444435
TI  - Frequency and significance of Pro12Ala and Pro115Gln polymorphism in gene for
      peroxisome proliferation-activated receptor-gamma regarding metabolic parameters
      in a Caucasian cohort.
AB  - Peroxisome proliferation-activated receptor-gamma2 (PPARgamma2) is exclusively
      expressed in adipose tissue and belongs to the transcriptional regulators of
      adipocyte differentiation. Recently, two missense single-point mutations have
      been described in the PPARgamma2 gene: Pro12Ala and Pro115Gln. It was our aim to
      determine the frequency of these polymorphisms in a Caucasian cohort and to
      investigate their possible role in the pathogenesis of obesity, type 2 diabetes,
      and related metabolic disorders. The genotypes of 359 subjects (149 males, 210
      females) with varying degrees of obesity and with or without type 2 diabetes were
      determined. Subsequent to genomic polymerase chain reaction amplification, the
      HpaII restriction fragment length polymorphism (RFLP) analysis and the HindII
      RFLP analysis were used for genotyping the Pro12Ala and Pro115Gln polymorphism,
      respectively. For the Pro115Gln polymorphism, all 359 subjects showed wild-type
      sequence, emphasizing the very rare occurrence of the mutated allele. For the
      Pro12Ala polymorphism, 276 subjects (76.9%) were homozygous for the wild-type
      allele, 80 (22.3%) were heterozygous, and only 3 (0.8%) were homozygous for the
      mutated allele. Genotype frequency was calculated to be 0.88 for the wild-type
      allele and 0.012 for the mutated allele. No significant differences were found in
      age; gender; body mass index; total cholesterol; low-density, high-density, and
      very low density lipoproteins; triglycerides; Lp(a); uric acid; and diabetes
      manifestation by comparing the different genotypes. Therefore, a major role of
      these polymorphisms in the pathogenesis of obesity and diabetes can be excluded.

PMID- 11444436
TI  - Impact of maternal undernutrition on hypothalamo-pituitary-adrenal axis and
      adipocyte functions in male rat offspring.
AB  - Malnutrition induces profound deleterious effects on several metabolic and
      neuroendocrine functions. In the present study, we examined the impact of
      maternal food restriction, during gestation and lactation, on the metabolic
      neuroendocrine function of their male offspring at 21 and 60 d of age. Well
      nourished (WN) and undernourished (UN) pregnant rats were used, during gestation
      and lactation, until pups were weaned. Twenty-one-day-old WN and UN male pups
      were studied in basal and postinsulin conditions. Additional groups of weaned (WN
      and UN) male rats were fed either ad libitum (WN-WN and UN-WN) or in a restricted
      fashion (WN-UN and UN-UN) until experimentation at age 60 d. Body weights of
      mothers and their male offspring were monitored. Basal and postinsulin plasma
      concentrations of several metabolic fuels were evaluated. Our results indicate
      that 21-d-old UN male rats exhibited (vs their WN counterparts), decreased body
      weights, similar basal and postinsulin glycemia, similar basal plasma
      adrenocorticotropic hormone (ACTH) and corticosterone levels but diminished ACTH
      response to insulin treatment, and basal hypoleptinemia and significant insulin
      induced leptin release. Finally, at 60 d of age, long-term UN (WN-UN and UN-UN)
      rats showed lower plasma (basal and postinsulin) glucose, and basal triglyceride
      levels than their counterparts (WN-WN and UN-WN). Sixty-day-old rats submitted to
      either food restriction protocol also showed a reduced hypothalamo-pituitary
      adrenal axis response to insulin-induced hypoglycemia and basal hypoleptinemia,
      in spite of restoration of normal body weights. These results further indicate a
      clear metabolic-neuroendocrine dysfunction in male pups of UN mothers, with the
      abnormality partially present at weaning and deteriorated by adulthood, even
      after the recovery of normal body weight. Our study strongly supports the
      importance of the irreversibility of a deleterious allostatic state resulting
      from fetal and early postnatal undernutrition.

PMID- 11444437
TI  - Labeling of pancreatic glycogen by D-[U-14c]glucose in hyperglycemic rats.
AB  - Under conditions of sustained hyperglycemia, glycogen accumulates in pancreatic
      islets, but not so in acinar pancreatic cells. We investigated whether advantage
      could be taken of such a situation in the perspective of the noninvasive imaging
      of the endocrine pancreas. Control rats or animals injected with streptozotocin
      (STZ) were infused with solutions of D-glucose mixed with a tracer amount of D-[U
      14C]glucose, and the radioactive glycogen content of both liver and pancreas was
      then measured. After 48 h of infusion, the radioactive glycogen content of the
      pancreas was 30 times lower in STZ rats than in control animals, coinciding with
      a 50 times lower insulin content. In the control rats, a sizable labeling of
      pancreatic glycogen was also recorded when D-[U-14C]glucose was infused for only
      the last 4 h of unlabeled D-glucose infusion; such a labeling was not decreased
      when the animals were further infused for 1 h with only the unlabeled hexose.
      Moreover, a pronounced difference in the pancreatic gland and blood radioactive
      content of control rats was still observed when the hyperglycemic animals were
      killed only 40 min after the i.v. injection of D-[U-14C]glucose. In STZ rats
      transplanted with islets and later infused with D-[U-14C]glucose, the total
      radioactive content and radioactive glycogen content were both much higher in the
      transplanted islets than in the pancreatic gland. These results allow one to
      define the conditions under which the administration of either 2-deoxy-2
      [18F]fluoro-D-glucose or 11C-labeled D-glucose could conceivably be used to favor
      the selective labeling of the endocrine, as distinct from exocrine, pancreas.

PMID- 11444438
TI  - Insulin-like growth factor binding proteins in the bovine anterior pituitary.
AB  - Insulin-like growth factor binding proteins (IGFBPs) were characterized in bovine
      anterior pituitary tissue, pituitary conditioned media, and serum collected
      during the preovulatory and early luteal phases of the estrous cycle. Effects of
      in vitro treatments of pituitaries with luteinizing hormone-releasing hormone
      (LHRH), estradiol, and progesterone on IGFBP secretion were also evaluated.
      Predominant IGFBPs detected in anterior pituitary tissue by immunoprecipitation,
      ligand blotting, and Northern blotting were IGFBP-5 (29 kDa), IGFBP-2 (32 kDa),
      and IGFBP-3 (36 and 39 kDa doublet). Conditioned culture media contained IGFBP-5,
      a slightly larger form of IGFBP-2 (33 kDa), the 36- and 39-kDa forms of IGFBP-3,
      and a more extensively glycosylated form of IGFBP-3 (44 kDa). In serum, IGFBP-5
      was not readily detected, and IGFBP-3 (40- and 44-kDa doublet) and IGFBP-2 (34
      kDa) were larger than in pituitary tissue. Levels of IGFBP-2, -3, and -5 in
      pituitary tissue decreased during the preovulatory period and were lowest in the
      early luteal phase. Treatment with LHRH increased IGFBP-2 levels in media
      twofold. Estradiol or progesterone did not alter IGFBP secretion in vitro.
      Predominant IGFBPs produced and released by anterior pituitary tissue were IGFBP
      2, -3 and -5. The activity of IGFBPs fluctuates in the pituitary in association
      with changes in stage of estrous cycle, implicating IGFBPs as potential
      regulators of gonadotrope function.

PMID- 11444439
TI  - Ovarian hormones elicit phosphorylation of Akt and extracellular-signal regulated
      kinase in explants of the cerebral cortex.
AB  - Estradiol and progesterone both have been demonstrated to afford neuroprotection
      against various insults. In an attempt to identify potential mechanisms
      underlying these neuroprotective effects, two key elements within signal
      transduction pathways linked to neuroprotection were evaluated. In mouse cerebral
      cortical explants, both estradiol and progesterone elicited the phosphorylation
      of Akt, a downstream effector of the phosphoinositide-3 (PI-3) kinase pathway.
      Progesterone also elicited the phosphorylation of extracellular-signal regulated
      kinase (ERK), a component of the mitogen-activated protein kinase (MAPK) pathway.
      These effects were not inhibited by the progesterone receptor antagonist, RU486.
      However, inhibition of either MAPK/ERK kinase with PD98059 or PI-3 kinase with
      LY294002 successfully inhibited progesterone's actions on ERK and Akt,
      respectively. Collectively, the data offer novel mechanisms for both progesterone
      and estrogen action in the central nervous system, demonstrating the functional
      and mechanistic diversity of gonadal hormones and supporting their
      neuroprotective potential for such neurodegenerative disorders as Alzheimer
      disease.

PMID- 11444440
TI  - Steroid hormone receptors in target cell membranes.
AB  - Numerous reports of rapid steroid hormone effects in diverse cell types cannot be
      explained by the generally prevailing theory that centers on the activity of
      hormone receptors located exclusively in the nucleus. Cell membrane forms of
      steroid hormone receptors coupled to intracellular signaling pathways may also
      play an important role in hormone action. Membrane-initiated signals appear to be
      the primary response of the target cell to steroid hormones and may be
      prerequisite to subsequent genomic activation. Recent dramatic advances in this
      area have intensified efforts to delineate the nature and biologic roles of all
      receptor molecules that function in steroid hormone-signaling pathways. This work
      has profound implications for our understanding of the physiology and
      pathophysiology of hormone actions in responsive cells and may lead to
      development of novel approaches for the treatment of many cell proliferative,
      metabolic, inflammatory, reproductive, cardiovascular, and neurologic defects.

PMID- 11444441
TI  - Effects of weight loss on leptin, sex hormones, and measures of adiposity in
      obese children.
AB  - Adipose tissue influences steroid conversion by paracrine and autocrine
      mechanisms. Leptin is secreted by adipocytes and influenced by sex hormones and
      adiposity. Short-term weight loss in the treatment of childhood obesity reduces
      leptin and adipose tissue. We therefore asked, Do alterations in sex hormones
      occur owing to weight loss? and can these alterations be explained by changes in
      fat mass or sc fat and are alterations in sex hormones directly related to the
      fall in leptin? Twenty obese boys and 40 obese girls were studied before and
      after 3 wk of low-calorie diet and physical activity. The weight loss program
      significantly lowered fat mass, abdominal fat distribution, sc fat (all p <
      0.0001), leptin, insulin, and estradiol (all p < 0.0001) but not testosterone.
      Changes in leptin were related to changes in body mass and to changes in fat mass
      in boys. In girls, changes in leptin were related to changes in sc fatness and
      also to changes in insulin. In boys, the reduction in sc fat was positively
      correlated to changes in testosterone (r = 0.54; p < 0.01) and inversely related
      to the fall in estradiol (r = -0.41; p < 0.05). In girls, changes in testosterone
      (r = 0.33; p < 0.05) and in estradiol (r = 0.40; p < 0.01) were related to
      changes in insulin. Stepwise regression showed that initial leptin was the best
      determinant for the fall in leptin (adjusted R2 = 0.87; p < 0.0001). The results
      show that alterations in sex hormones are related to changes in certain fat
      depots in boys whereas in girls changes in insulin might participate in changes
      in sex hormones. A greater fall in leptin owing to short-term weight loss is not
      associated with greater alterations in sex hormones and initial leptin is the
      best determinant to explain the variability in changes in leptin. The possibility
      of sex differences in changes in sex hormones secondary to the reduction in
      fatness warrants further study.

PMID- 11444442
TI  - Detecting coagulation disorders of pregnancy: bleeding time or platelet count?

PMID- 11444443
TI  - CSE for labour: the debate goes on ..

PMID- 11444444
TI  - Clonidine as adjuvant for mepivacaine, ropivacaine and bupivacaine in axillary,
      perivascular brachial plexus block.
AB  - PURPOSE: To evaluate the effects of clonidine on three local anesthetics
      (mepivacaine 1%, ropivacaine 0.75% and bupivacaine 0.5%) with comparable potency
      and almost the same concentration-response relationship. METHODS: One hundred and
      twenty trauma-patients were randomly allocated into six groups. In the control
      groups (Mo/Ro/Bo) brachial plexus was performed using 40 mL of local anesthetic
      plus 1 mL of NaCL 0.9%. In the clonidine-groups (Mc/Rc/Bc) brachial plexus was
      performed using each 40 mL of drug plus 1 mL (0.150 mg) of clonidine. Onset-time
      and the duration of the sensory block were recorded. Data are expressed as mean
      +/- SD. RESULTS: According to the average sensory block determined by a visual
      analog scale in the median, ulnar and radial nerve distributions and ranging from
      100 (no sensory blockade) to 0 (complete sensory blockade), both mepi-groups
      showed a rapid onset (at 10 min: -Mo 20 +/- 15/Mc 19 +/- 14; at 30 min: -Mo 3 +/-
      4/Mc 5 +/- 4). The ropi-and bupi- groups both had a longer onset time (at 10 min:
      -Ro 23 +/- 19/Rc 25 +/- 22/Bo 24 +/- 15; at 30 min -Ro 10 +/- 6/ Rc 11 +/- 6 /Bo
      12 +/- 4). The onset time in group-Bc was significantly prolonged (at 10 min: -45
      +/- 21; at 30 min: -20 +/- 6). Duration of motor blockade was prolonged by
      clonidine only in the mepivacaine and bupivacaine groups; (in minutes: Mo 212 +/-
      47 -Mc 468 +/- 62; Ro 702 +/- 52 -Rc 712 +/- 82; Bo 728 +/- 36 -Bc 972 +/- 72).
      CONCLUSION: The present study shows that the addition of clonidine has a
      different impact on each of the three local anesthetics investigated in terms of
      onset and duration of block.

PMID- 11444445
TI  - Anesthetic considerations in a patient with visceral leishmaniasis.
AB  - PURPOSE: To describe the anesthetic problems in a patient with visceral
      leishmaniasis undergoing general anesthesia. CLINICAL FEATURES: A 17-yr-old man
      with visceral leishmaniasis was booked for emergency appendectomy. He received
      parentral sodium stibogluconate 600 mg per day. The patient was pale, afebrile
      and had hepatosplenomegaly. Preoperative investigations showed a hemoglobin of
      6.2 g.dL(-1), platelet count of 80 x 10(9).L(-1) and serum albumin of 2.1 g.dL(
      1). The electrocardiogram and chest x-ray were normal. Anesthesia was induced
      with 100 microg fentanyl and 50 mg propofol iv and tracheal intubation was
      facilitated with 3 mg vecuronium iv. Maintenance of anesthesia was done with
      intermittent positive pressure ventilation using 50% nitrous oxide and 0.4%
      isoflurane in oxygen. Reversal of neuromuscular blockade was achieved with 1.0 mg
      neostigmine and 0.2 mg atropine iv. 50 mg tramadol iv every six hours was used
      for postoperative analgesia. The perioperative course was uneventful. CONCLUSION:
      Patients with visceral leishmaniasis have problems unique to them that may
      influence the anesthetic management. Of particular concern to an anesthesiologist
      are the presence of hematological abnormalities (anemia, leukopenia,
      thrombocytopenia), and hypoalbuminic malnutrition. The combination of low
      hemoglobin and thrombocytopenia may necessitate blood component therapy
      perioperatively. Drugs affecting coagulation should be used judiciously.
      Hypoalbuminemia may adversely affect the pharmacokinetics of agents that are
      highly protein bound. The anesthetic management in a patient with visceral
      leishmaniasis may be further complicated by the presence of coexisting infections
      like pneumonia and tuberculosis. Leishmaniasis is a recognized complication of
      infection with human immunodeficiency virus.

PMID- 11444446
TI  - Desflurane reduces the effective therapeutic infusion rate (ETI) of cisatracurium
      more than isoflurane, sevoflurane, or propofol.
AB  - PURPOSE: The present study investigated the interaction between the cumulative
      dose requirements of cisatracurium and anesthesia with isoflurane, sevoflurane,
      desflurane or propofol using closed-loop feedback control. METHODS: Fifty-six
      patients (18-85 yr, vitrectomies of more than one hour) were studied. In the
      volatile anesthetics groups, anesthesia was maintained by 1.3 MAC of isoflurane,
      sevoflurane or desflurane; in the propofol group, anesthesia was maintained by a
      continuous infusion of 6-8 mg.kg(-1).hr(-1) propofol. After bolus application of
      0.1 mg.kg(-1) cisatracurium, a T1%-level of 10% of control level (train-of-four
      stimulation every 20 sec) was maintained using closed-loop feedback controlled
      infusion of cisatracurium. The effective therapeutic infusion rate (ETI) was
      estimated from the asymptotic steady-state infusion rate Iss. The Iss was derived
      from fitting an asymptotic line to the measured cumulative dose requirement
      curve. The ETI of the different groups was compared using Kruskal-Wallis- test,
      followed by rank sum test, corrected for the number of comparisons, P <0.05 was
      regarded as showing significant difference. RESULTS: ETI in the isoflurane group
      was 35.6 +/- 8.6 microg.m(-2).min(-1), in the sevoflurane group 36.4+/- 11.9
      microg m(-2).min(-1), in the desflurane group 23.8 +/- 6.3 microg.m(-2).min(-1).
      The ETI of the volatile anesthetic groups were all significantly lower than the
      ETI in the propofol group at 61.7 +/- 25.3 microg.m(-2).min(-1) (P <0.002). The
      ETI in the desflurane group was significantly lower than in all other groups (P
      <0.02). CONCLUSION: In comparison to propofol, isoflurane, sevoflurane and
      desflurane reduce the cumulative dose requirements of cisatracurium to maintain a
      90% neuromuscular blockade by 42%, 41% and 60%, respectively.

PMID- 11444447
TI  - Epidural anesthesia with lidocaine reduces propofol injection pain.
AB  - PURPOSE: To determine whether epidural lidocaine reduces the severity of propofol
      injection pain compared with iv lidocaine. METHODS: A prospective, randomized
      double-blind clinical study was conducted in 120 female patients scheduled for
      elective gynecological laparotomy. A lumbar epidural catheter and an iv catheter
      placed in the cephalic vein of the non-dominant hand were used in all patients.
      Patients of the control group (Group C) were given epidural normal saline
      followed by iv normal saline then iv propofol. Patients of Group E were given
      epidural 2% lidocaine (0.08 mL.cm(-1)) followed by iv normal saline and then
      propofol. Patients of Group V were given epidural normal saline followed by iv 2%
      lidocaine (0.05 mL.kg(-1)) then propofol. Pain was scored as no pain=0, minimal
      pain=1, moderate pain=2, severe pain=3. RESULTS: The pain scores, in group E; 1
      (0-2) and group V; 2 (0-2), were significantly lower than in group C; 2 (1-3);
      median (25th-75th percentile) (P <0.001). There was no difference in pain score
      between groups E and V The plasma lidocaine concentration 15 min after epidural
      lidocaine was 2.74 +/- 0.54 microg.ml(-1), compared with 1.54 +/- 0.31 microg.mL(
      1) at three minutes after iv lidocaine. CONCLUSION: Epidural and iv lidocaine
      equally reduced the severity of propofol injection pain despite higher lidocaine
      plasma concentrations in epidurally administered lidocaine.

PMID- 11444448
TI  - Pain after laparoscopic cholecystectomy: the effect and timing of incisional and
      intraperitoneal bupivacaine.
AB  - PURPOSE: To examine the combined preemptive effects of somatovisceral blockade
      during laparoscopic cholecystectomy (LC). METHODS: One hundred fifty-seven
      patients under general anesthesia receiving local infiltration and/or topical
      peritoneal local anesthesia were studied. Patients were randomized to receive a
      total of 150 mg (0.25% 60 mL) bupivacaine via periportal (20 mL) and
      intraperitoneal (40 mL with 1:200,000 epinephrine) administration of each. Group
      A received preoperative periportal bupivacaine before incision and
      intraperitoneal bupivacaine immediately after the pneumoperitoneum. Group B
      received periportal and intraperitoneal bupivacaine at the end of the operation.
      Group C (preoperative) and Group D (postoperative) received only periportal
      bupivacaine and Group E (preoperative) and Group F (post-operative) received only
      intraperitoneal bupivacaine. The control group received no treatment. Pain and
      nausea were recorded at one, two, three, six, nine, 12, 24, 36, and 48 hr
      postoperatively. RESULTS: Throughout the postoperative 48 hr, incisional somatic
      pain dominated over other pain localizations in the control group (P <0.05). The
      incisional pain of groups A, B, C and D was significantly lower than that of the
      control group in the first and second hours. The incisional pain of groups A and
      C was significantly lower than that of the control group in the first three
      hours. CONCLUSION: Incisional pain dominated during the first two post-operative
      days after LC. Preoperative somato-visceral or somatic local anesthesia reduced
      incisional pain during the first three post-operative hours. A combination of
      somato-visceral local anesthetic treatment did not reduce intraabdominal pain,
      shoulder pain or nausea more than somatic treatment alone. Preoperative
      incisional infiltration of local anesthetics is recommended.

PMID- 11444449
TI  - Intrathecal bupivacaine with morphine or neostigmine for postoperative analgesia
      after total knee replacement surgery.
AB  - PURPOSE: To compare the postoperative analgesic efficacy and safety of
      intrathecal (IT) neostigmine and IT morphine in patients undergoing total knee
      replacement under spinal anesthesia. METHODS: Sixty patients scheduled for
      elective total knee replacement under spinal anesthesia were randomly divided
      into three equal groups which received IT 0.5% hyperbaric bupivacaine 15 mg with
      either normal saline 0.5 mL, neostigmine 50 microg, or morphine 300 microg. The
      maximal level of sensory block, duration of analgesia, time to use of rescue
      analgesics, the overall 24-hr and four-hour interval visual analogue scale (VAS)
      pain score, and the incidence of adverse effects were recorded for 24 hr after
      administration. RESULTS: There was no significant difference in maximal level of
      sensory block among the three groups. The morphine group had a later onset of
      postsurgical pain and longer time to first rescue analgesics than the neostigmine
      group (P <0.05). Overall 24-hr VAS pain scores were significantly higher in the
      saline group vs the morphine and neostigmine groups (P <0.05). Motor block lasted
      significantly longer in the neostigmine group than in the morphine and saline
      groups (P <0.05). The incidence of adverse effects was similar in the neostigmine
      and morphine groups except for pruritus (70%) occurring more frequently in the
      morphine group than in the neostigmine and saline groups (0%; P <0.05). Overall
      satisfaction rates were better in the neostigmine group than in the morphine and
      saline groups (P <0.05). CONCLUSIONS: IT neostigmine 50 microg produced
      postoperative analgesia lasting about seven hours with fewer side effects and
      better satisfaction ratings than IT morphine 300 microg.

PMID- 11444450
TI  - Left ventricular contractility is reduced by hypercapnic acidosis and
      thoracolumbar epidural anesthesia in rabbits.
AB  - PURPOSE: We have previously observed that sympathetic blockade by epidural
      anesthesia (EA) modifies the cardiovascular response to marked hypercapnic
      acidosis in dogs. Our objective was to determine whether the combination of
      marked hypercapnic acidosis and EA reduce left ventricular contractility.
      METHODS: We randomly assigned 22 Japanese white rabbits anesthetized with
      isoflurane (1.0%) to two groups according to the absence (control group, n= 11)
      or presence (EA group, n= 11) of thoracolumbar EA. After epidural injection (0.5
      mL.kg(-1) of 0.9% saline in the control group or 1% mepivacaine in the EA group)
      and during subsequent hypercapnia (mean arterial CO2 tension 85 mmHg), we
      measured left ventricular pressure, left ventricular volume by using conductance
      catheter and plasma catecholamine concentrations. Left ventricular contractility
      was assessed by the slope of the linear approximation of the left ventricular end
      systolic pressure-volume relationship, [i.e., end-systolic elastance (Ees)].
      RESULTS: The combination of hypercapnic acidosis and thoracolumbar EA caused a
      65% decrease in Ees (P <0.05). Hypercapnic acidosis alone caused a 16% decrease
      (P <0.05) and thoracolumbar EA alone caused a 49% decrease in Ees (P <0.05). In
      the EA group, epidural injection caused an 85% decrease in the epinephrine
      concentration (P <0.05) and a 39% decrease in the norepinephrine concentration (P
      <0.05), even during hypercapnic acidosis. However, in the control group,
      hypercapnic acidosis caused no change in the circulating epinephrine
      concentration but a 74% increase in the circulating norepinephrine concentration
      (P <0.05). CONCLUSION: Combined hypercapnic acidosis and EA markedly reduce left
      ventricular contractility in an additive fashion in rabbits receiving general
      anesthesia.

PMID- 11444451
TI  - Platelet count may predict abnormal bleeding time among pregnant women with
      hypertension and preeclampsia.
AB  - BACKGROUND: Anesthesiologists often require laboratory data to estimate the
      bleeding risk among hypertensive pregnant women prior to administering regional
      anesthesia. Many rely on the bleeding time (BT) in making this determination. We
      examined whether the platelet count can adequately predict BT among a group of
      hypertensive parturients. METHODS: This retrospective subgroup analysis, taken
      from a cohort of 2,051 hypertensive pregnant women, comprises 87 individuals who
      underwent both a BT and platelet count prior to delivery. We calculated the
      correlation between the platelet count and BT at three platelet cut-off points
      with respect to prolonged BT of eight minutes or more. RESULTS: There was a
      significant negative correlation between platelet count at delivery and BT [r= 
      0.45, 95% confidence interval (CI) -0.26 to -0.60; P <0.0001]. All three platelet
      cut-off points had a sensitivity of less than 66% with negative predictive values
      below 75% for an abnormal BT. A platelet count > or =75 x 109/L [corrected] was
      specific for the presence of an abnormal BT (specificity 97.8%, 95% CI 91.7
      100.0), with a positive predictive value of 95.5% (95% CI 83.1-100.0) and a
      positive likelihood ratio of 24 (95% CI 3.3-168). CONCLUSIONS: In a group of
      hypertensive parturients, the platelet count appears to be very specific for
      predicting a prolonged BT The platelet count may aid the anesthesiologist in
      determining the risk of bleeding from regional anesthesia. Given the study's
      potential for bias future research is needed to validate these findings.

PMID- 11444452
TI  - Either sufentanil or fentanyl, in addition to intrathecal bupivacaine, provide
      satisfactory early labour analgesia.
AB  - PURPOSE: The study was aimed primarily at comparing the duration of analgesia
      produced by intrathecal fentanyl 25 microg with sufentanil 5 microg when added to
      bupivacaine 1.25 mg as the initial component of the combined spinal epidural
      (CSE) technique in early labour. METHODS: Forty healthy parturients were randomly
      assigned into two groups to receive either intrathecal sufentanil 5 microg plus
      bupivacaine 1.25 mg (Group S) or intrathecal fentanyl 25 microg plus bupivacaine
      1.25 mg (Group F). Apart from the duration of analgesia, pain scores and side
      effects were also evaluated. RESULTS: There was no significant difference in the
      duration of analgesia (mean 109 +/- SD 49 min in Group F vs 118 +/- 54 min in
      Group S, P=0.9). Group F had a more rapid onset of analgesia (P <0.05) and a
      higher cephalad block (median T4 vs T7, P <0.05) in the first 30 min after the
      block. No difference in the side effects was detected. CONCLUSION: Fentanyl 25
      microg is a good alternative to sufentanil 5 microg when added to bupivacaine
      1.25 mg for early labour analgesia.

PMID- 11444453
TI  - Clinical case discussion: anesthesia for Cesarean section in a parturient with a
      large intrathoracic tumour.
AB  - PURPOSE: To report the anesthetic management of a parturient with a large
      intrathoracic tumour, presenting for Cesarean section. CLINICAL FEATURES: A 28-yr
      old parturient, gravida 1, presented at 33 weeks gestation with a one month
      history of increasing cough and dyspnea. A computed tomography scan demonstrated
      a large mass filling the right hemothorax, causing mediastinal displacement to
      the left and carinal compression. Both mainstem bronchi were compressed and there
      was near total obliteration of the lumens of the right lobar bronchi. A decision
      was taken to expedite delivery to allow for staging and treatment of her disease
      and Cesarean section was scheduled. She was seen in consultation and prescribed
      oxygen by nasal prongs, dextromethorphan for cough and ranitidine the evening
      before and the morning of surgery. A subarachnoid block was performed and a block
      to the upper thoracic dermatomes was achieved; surgery proceeded uneventfully
      with the patient's head and upper body elevated about 15 degrees from the supine.
      The patient was discharged to the medical oncology service for evaluation and
      treatment. CONCLUSIONS: Intrathoracic tumours are uncommon in pregnancy. The
      physiological changes of pregnancy may mask not only the initial presentation but
      also, even advanced intrathoracic disease. Regional anesthesia is the anesthetic
      of choice and is rarely contraindicated by maternal condition.

PMID- 11444454
TI  - Use of inhaled nitric oxide for emergency Cesarean section in a woman with
      unexpected primary pulmonary hypertension.
AB  - PURPOSE: Use of inhaled nitric oxide (iNO) could be of importance in emergency
      cases of primary pulmonary hypertension (PPH) in pregnant patients during labour
      and delivery. iNO acts as a selective pulmonary bed vasodilator avoiding systemic
      hemodynamic effects due to its ease of administration. Pulmonary bed vasodilation
      improves right ventricular function directly and left ventricular function
      indirectly. CLINICAL FEATURES: We report the case of a pregnant patient with
      unexpected PPH in whom an emergency Cesarean section (CS) had to be performed.
      PPH was diagnosed on admission as she arrived in active labour at 34 weeks
      gestational age. An emergency CS was performed under epidural anesthesia for
      breech presentation . All along labour, delivery and the first 24 hr, iNO was
      administered via a noninvasive ventilation device. CS was uneventful. A severe
      pulmonary hypertensive crisis was observed 12 hr after delivery and resolved with
      an increase of iNO concentration and administration of isoprenalin. The patient
      and baby returned home on day ten. CONCLUSION: The ease of administration of iNO
      allowed the optimal control of pulmonary arterial hypertension. No interaction
      with epidural anesthesia was observed. Use of iNO can improve the management of
      urgent CS in women with unexpected PPH.

PMID- 11444455
TI  - Perioperative management of biventricular failure after closure of a long
      standing massive arteriovenous fistula.
AB  - PURPOSE: To report the perioperative management of arteriovenous fistula (AVF)
      closure in a patient with high-output heart failure and pulmonary hypertension.
      CLINICAL FEATURES: In a 71-yr-old man, closure of a long-standing massive AVF
      between the right femoral artery and vein was performed. After closure of the
      AVF, his pulmonary artery pressure (PAP) increased from 52/21 mmHg to 68/26 mmHg,
      his cardiac index decreased from 5.27 L.min(-1).m(-2) to 3.18 L.min(-1).m(-2),
      and his pulmonary wedge pressure increased from 15 mmHg to 32 mmHg due to an
      acute increase in afterload. Co-administration of prostaglandin E and a
      phosphodiesterase III inhibitor improved the cardiac index and the PAP.
      CONCLUSIONS: Surgical closure of the fistula may not always lead to resolution of
      the high output cardiac failure. In this case, afterload management using
      arterial dilators (prostaglandin E1, phosphodiesterase III inhibitor), use of
      inotropic drugs (phosphodiesterase III inhibitor), and close attention to volume
      status was crucial for a successful outcome after surgical AVF closure.

PMID- 11444456
TI  - Lightwand intubation using the Trachlight: a brief review of current knowledge.
AB  - PURPOSE: About 1% to 3% of laryngoscopic intubations can be difficult or
      impossible. Light-guided intubation has been proven to be an effective, safe, and
      simple technique. This article reviews current knowledge about the newer version
      lightwand: the Trachlight (TL). SOURCE: To determine its clinical utility and
      limitations, we reviewed the current literature (book and journal articles) on
      the TL since its introduction in 1995. PRINCIPAL FINDINGS: TL has been shown to
      be useful both in oral and nasal intubation for patients with difficult airways.
      It may also be useful in "emergency" situations or when direct laryngoscopy or
      fiberoptic endoscopy is not effective, such as with patients who have copious
      secretions or blood in the oropharynx. TL can also be used for tracheal
      intubation in conjunction with other devices (laryngeal mask airway -LMA-,
      intubating LMA, direct laryngoscopy). However, TL should be avoided in patients
      with tumours, infections, trauma or foreign bodies in the upper airway.
      CONCLUSIONS: Based on the clinical reports available, the TL has proven to be a
      useful option for tracheal intubation. In addition, the device can also be used
      together with other intubating devices, such as the intubating LMA and the
      laryngoscope, to improve intubating success rates. A clear understanding of the
      principle of transillumination of the TL, and an appreciation of its indications,
      contraindications, and limitations, will improve the effectiveness of the device
      as well as reducing the likelihood of complications. Finally, regular practice
      with the TL with routine surgical patients requiring tracheal intubation will
      further improve intubation success rates.

PMID- 11444457
TI  - Removal of the connector on the laryngeal mask airway provides a useful
      alternative to the intubating laryngeal mask.
AB  - PURPOSE: We describe two cases in which fiberoptic intubation through the
      standard laryngeal mask airway (LMA) was successful with large-bore tracheal
      tubes (TTs) when an intubating LMA (ILMA) could not be used. CLINICAL FEATURES:
      Patient # 1, with obstructive sleep apnea, underwent elective surgical repair.
      His mouth opening was just under 25 mm, but difficult intubation was not
      anticipated. We induced general anesthesia, easily ventilated the patient by
      mask, and established neuromuscular blockade. Direct laryngoscopy and attempts to
      insert either a #5 or a #4 ILMA into the mouth failed. A standard #4 LMA, with
      the connector removed, was inserted, through which a 7.0 mm nasal RAE TT,
      fiberoptically guided, passed into the trachea at the first attempt. Patient #2,
      with a loosened implant after left hip arthroplasty, underwent revision
      prosthesis. Her neck movement was limited. We thus planned awake securing of the
      airway, but the patient refused. We induced anesthesia and established bag-mask
      valve ventilation. The limited neck movement prevented direct laryngoscopy.
      Visualizing the laryngeal inlet with the fiberoptic bronchoscope (FOB) proved
      impossible as bloody secretions obscured the FOB's tip. Ventilation by mask was
      easy. As an ILMA was not available, we removed a #5 LMAs connector and passed an
      8.0 mm nasal RAE TT through the LMA. Fiberoptic-guided intubation was easy. In
      both cases, the remainder of the intraoperative course was uneventful.
      CONCLUSION: A standard LMA whose connector has been removed to allow passage of
      TTs of >6.0 mm internal diameter may be substituted for the ILMA when necessary.

PMID- 11444458
TI  - Routine use of the intubating laryngeal mask airway results in increased upper
      airway morbidity.
AB  - PURPOSE: The classic laryngeal mask airway (LMA) has a soft, silicone tube and
      the intubating laryngeal mask airway (ILM) has a rigid, silicone-coated steel
      tube. We compare postoperative pharyngolaryngeal morbidity in patients randomised
      to receive either device. METHODS: Sixty-five female patients (ASA physical
      status class I or II, aged 18-80 yr) undergoing balanced regional anesthesia for
      gynecological laparotomy expected to last one to two hours were randomly assigned
      for airway management with the LMA or ILM. Intracuff pressure was maintained at
      60 cm H20. Postoperative pharyngolaryngeal morbidity (sore throat, difficulty
      swallowing, sore mouth, sore neck/jaw, hoarseness) was assessed at two, 24 and 48
      hr by blinded investigators. RESULTS: The number of insertion attempts and
      duration of anesthesia was similar between groups. Sore throat was more common
      for the ILM at two hours (44 vs 15%, P=0.01), 24 hr (59 vs 21%, P=0.008) and 48
      hr (34 vs 3%, P=0.005). Sore mouth was more common for the ILM at two hours (16
      vs 0%, P=0.02) and 24 hr (12 vs 0%, P=0.04), but not at 48 hr (6 vs 3%).
      Difficulty swallowing was more common for the ILM at two hours (25 vs 0%,
      P=0.04), but not at 24 hr (31 vs 3%) and 48 hr (12 vs 9%). There were no
      differences in the incidence of sore jaw/neck (ILM, 3-12%; LMA, 0-3%) and
      hoarseness (ILM, 12-31%; LMA, 16-18%). There was no correlation between
      postoperative pharyngolaryngeal morbidity and duration of anesthesia. CONCLUSION:
      Pharyngolaryngeal morbidity is more common with the ILM than the LMA following
      anesthesia lasting one to two hours.

PMID- 11444459
TI  - Special challenges with new digital anesthesia machines.

PMID- 11444460
TI  - Epidural anesthesia and splanchnic perfusion.

PMID- 11444461
TI  - Good advice on airways, but measurements are not parameters.

PMID- 11444462
TI  - Convulsions after the administration of high dose ropivacaine following an
      interscalenic block.

PMID- 11444463
TI  - Medication safety in anesthetic practice.

PMID- 11444464
TI  - What role, if any, for laparoscopic surgery in Crohn disease of the hindgut?

PMID- 11444465
TI  - Helicobacter pylori and gastroesophageal reflux disease: to treat or not to
      treat?

PMID- 11444466
TI  - Expression of decorin and biglycan in rat gastric tissue: effects of ulceration
      and basic fibroblast growth factor.
AB  - BACKGROUND: The small chondroitin/dermatan sulphate proteoglycans decorin and
      biglycan participate in organizing the network of collagen fibrils and interact
      with non-collagenous matrix proteins. In addition, via interactions with
      cytokines they are directly or indirectly involved in signalling, growth and cell
      differentiation. We aimed to analyse their expression in normal gastric tissue
      and during gastric ulcer healing. METHODS: Proteoglycan expression was studied by
      immunohistochemistry and in situ hybridization in acetic acid-induced gastric
      ulcers in rat during early phases and during chronic ulceration. The effects of
      treatment with an acid stable mutein of FGF-2 (bFGF) were also studied. RESULTS:
      In normal gastric tissue, both proteoglycans were most strongly expressed in the
      submucosal layer. However, some epithelial cells were positive for biglycan and,
      surprisingly, also for decorin. In the early phase after ulcer induction
      exclusively decorin became induced in the muscularis mucosae, while biglycan
      became detectable in this layer only after 2 weeks. There was no up-regulation of
      either proteoglycan in other layers, nor could an effect of FGF-2 treatment be
      seen. CONCLUSIONS: The expression of decorin could be observed for the first time
      in epithelial cells. Decorin, but not biglycan, appears as an early phase
      reactant in the muscularis mucosae in accordance with its putative role during
      angiogenesis and the prevention of apoptosis.

PMID- 11444467
TI  - Pooled analysis on the efficacy of the second-line treatment regimens for
      Helicobacter pylori infection.
AB  - BACKGROUND: Although many of the currently available Helicobacter pylori
      eradication regimens fail to cure 5%-12% of patients, an optimal re-treatment
      therapy for eradication-failure patients has still not been established. The aim
      of this study was to examine all reports concerning the efficacy of re
      eradication regimens for H. pylori infection, and to establish optimal re
      eradication regimens. METHODS: Studies concerning re-eradication regimens were
      retrieved from the MEDLINE database, reference lists and major congress abstract
      lists up through December 1999. Data from all selected reports were pooled into
      several groups depending on second-line or initial therapies. Pooled eradication
      rates of re-treatment regimens were compared using Fisher's exact test (P <
      0.05). RESULTS: Sixteen articles and 24 abstracts with 75 total treatment arms
      were included in this study. Pooled re-eradication rates by proton-pump inhibitor
      (PPI)-based dual therapy, PPI-based triple therapy, ranitidine bismuth-based
      triple therapy and quadruple therapy were 45.8%, 69.8%, 80.2% and 75.8%,
      respectively. Eradication rates from studies with two new antimicobials added
      were higher than rates from studies with only one new antimicrobial added (P =
      0.0064). CONCLUSION: Ranitidine bismuth-based triple therapies, as well as
      quadruple therapies, seem to be the most effective re-treatment therapies in all
      currently undertaken therapies. The strategy of adding two new antimicrobials to
      previous regimens was also effective in re-eradication therapy.

PMID- 11444468
TI  - Helicobacter pylori and iron deficiency anaemia in children.
AB  - BACKGROUND: Both iron deficiency anaemia and Helicobacter pylori infection are
      rare in developed countries. A possible connection has been suggested between
      these two diseases and our aim was to define the clinical picture and to study
      the effect of bacterial eradication in H. pylori colonized children with severe
      anaemia. METHODS: Eight children with iron deficiency anaemia refractory to iron
      supplementation were examined with gastroscopy because of suspicion of H. pylori
      infection. Anaemia was treated with oral ferrous sulphate. Two patients needed
      blood transfusions. Eradication therapy was given either with combination of
      colloidal bismuth subcitrate and metronidazole or with omeprazole, clarithromycin
      and amoxycillin. Eradication was confirmed by urea breath test 4 weeks post
      treatment. RESULTS: H. pylori infection was confirmed histologically and
      microbiologically in all children, who also presented with chronic, active
      gastritis. Bacteria were successfully eradicated in 7/8 patients. Correction of
      haemoglobin values was observed post-treatment, iron stores still being deficient
      at control in 4/8 children. CONCLUSIONS: Our results suggest that H. pylori might
      have a role in causing iron deficiency anaemia in school-age children. Screening
      for H. pylori should be extended to cover those patients with other clinical
      manifestations than symptoms from gastrointestinal tract.

PMID- 11444469
TI  - Helicobacter pylori-induced expression of interleukin-8 and cyclooxygenase-2 in
      AGS gastric epithelial cells: mediation by nuclear factor-kappaB.
AB  - BACKGROUND: Helicobacter pylori infection might activate nuclear factor-kappaB
      (NF-kappaB), a transcriptional regulator of inducible expression of inflammatory
      genes, interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). We studied the role of
      NF-kappaB on expression of IL-8 and COX-2 in H. pylori-stimulated AGS gastric
      epithelial cells by using antisense oligonucleotide (AS ODN) for NF-kappaB
      subunit p50 and an antioxidant, glutathione (GSH) as well as a NF-kappaB
      inhibitor, pyrrolidine dithiocarbamate (PDTC). METHODS: AGS cells were treated
      with p50 AS ODN, GSH or PDTC in the presence of H. pylori. mRNA expression and
      protein levels for IL-8 and COX-2 were determined by Northern blot analysis and
      Western blot analysis. Levels of IL-8, 6-keto-prostaglandin F1alpha (6-keto
      PGF1alpha) and thromboxane B2 (TXB2) were measured in the medium by enzyme-linked
      immunosorbent assay. NF-kappaB activation was examined by electrophoretic
      mobility shift assay. RESULTS: H. pylori induced a time-dependent expression of
      mRNA and protein for IL-8 and COX-2 via activation of NF-kappaB and increased the
      levels of IL-8, 6-keto-PGF1alpha and TXB2, which were inhibited by GSH and PDTC.
      H. pylori-induced expression of IL-8 and COX-2 was blocked in AGS cells
      transfected with p50 AS ODN. CONCLUSION: NF-kappaB may play a novel role in
      expression of IL-8 and COX-2 in H. pylori-induced gastric inflammation.

PMID- 11444470
TI  - Helicobacter pylori and bleeding duodenal ulcer: prevalence of the infection and
      role of non-steroidal anti-inflammatory drugs.
AB  - BACKGROUND: Several authors have reported low prevalence of Helicobacter pylori
      infection in patients with upper gastrointestinal bleeding (UGIB). Our aim was to
      study the prevalence of H. pylori in bleeding duodenal ulcer (DU), with both
      invasive and non-invasive methods, and to assess the role of non-steroidal anti
      inflammatory drugs (NSAIDs). METHODS: Ninety-two patients with bleeding DU were
      prospectively studied. The use of NSAIDs was evaluated by specific questionnaire.
      As a control group, 428 patients undergoing outpatient evaluation for the
      investigation of dyspepsia and found to have a DU at endoscopy were included. At
      endoscopy, two antral biopsies were obtained (H&E stain). A 13C-urea breath test
      was carried out in all patients. Breath test was repeated in patients treated
      with omeprazole during the hospitalization if H. pylori was not detected with the
      first test. RESULTS: Gastric biopsies could be obtained in 39 patients with UGIB.
      Three patients with UGIB treated with omeprazole and being H. pylori-negative
      with the first breath test were finally considered infected with the second test.
      Overall, 92.4% (95% CI, 85%-96%) of the patients with UGIB were infected (89.7%
      with histology and 92.4% with breath test (P = 0.15)). Concordance kappa value
      for both diagnostic tests was 0.64. NSAID intake was more frequent in patients
      with UGIB (34%) than in those without UGIB (5.6%) (P < 0.001), while H. pylori
      infection was less frequent in patients with UGIB (92.4% (85%-96%)) than in those
      without UGIB (99.1% (98%-100%); P < 0.001). Even in patients with UGIB, NSAID
      intake was the only risk factor in 5% of cases. The proportion of cases without
      H. pylori infection and without NSAID intake was very low in both bleeding and
      non-bleeding ulcers (2% and 0.5%, respectively; P = 0.146). H. pylori prevalence
      in bleeding ulcers was of 84% (67%-93%) in patients with NSAID intake, and 96.7%
      (89%-99%) when patients taking NSAIDs were excluded. In the multivariate
      analysis, NSAID intake (odds ratio, 9.8 (5.2-18.4)) correlated with UGIB;
      however, neither H. pylori status nor the interaction between H. pylori infection
      and NSAID intake correlated with UGIB. In the multivariate analysis in the
      subgroup of patients with UGIB, NSAID use was the only variable which correlated
      with H. pylori prevalence (odds ratio, 0.18 (0.03-0.97)). CONCLUSIONS: The most
      important factor associated with H. pylori-negative bleeding DU is NSAID use, and
      if this factor is excluded prevalence of infection is almost 100% (97%), similar
      to that found in patients with non-bleeding DU (and without NSAID intake).
      Bleeding DU patients with neither H. pylori infection nor NSAID use are extremely
      rare (only 2%), which suggests that the pathogenesis of bleeding DU is similar to
      that of non-complicated DU disease.

PMID- 11444471
TI  - Impact of sex and psychological factors on the water loading test in functional
      dyspepsia.
AB  - BACKGROUND: The pathogenesis of upper abdominal symptoms in patients with
      functional dyspepsia (FD) is still unclear. The water loading test (WLT) is a new
      method for evaluation of gastric function. Our aim was to determine the impact of
      sex, age and psychological factors on the results of WLT in FD patients, FD
      subgroups and healthy controls (HCs), and to evaluate the safety of the test.
      METHODS: Fifty-six HCs and 35 consecutive patients with FD drank mineral water
      (100 ml/min) until intolerable. Serum samples for sodium, potassium and
      creatinine was taken before and after drinking. Water quantity was registered and
      symptoms were assessed after maximal water intake and 30 min later using a VAS
      scale. Participants also completed questionnaires measuring psychological general
      well-being (PGWB) and gastrointestinal symptoms (GSRS and Mearin score). RESULTS:
      Healthy men drank more than healthy women, 2350 +/- 105 ml versus 1860 +/- 100 ml
      (P < 0.01), and the same gender difference was noted in FD patients, 1770 +/- 115
      ml versus 1180 +/- 110 ml (P < 0.01). Maximal water intake was significantly
      higher in HC than in FD patients, both in males (P < 0.001) and females (P <
      0.0001). Age had no impact on drinking capacity. FD patients had more symptoms 30
      min after maximal water intake than HCs. Serum sodium decreased from 141 +/- 0.3
      mmol/l to 138 +/- 0.5 mmol/l. Two of the assessed psychological factors, general
      health and depressed mood, correlated with water intake in FD patients (Rho =
      0.47, P < 0.01 respectively Rho = 0.41, P < 0.05). CONCLUSION: WLT is a useful,
      simple and safe test for evaluating symptoms in FD patients. Sex, but not age
      affects the results of the WLT. Furthermore, psychological factors must also be
      taken into consideration when interpreting the WLT.

PMID- 11444472
TI  - Antisecretory effect of loperamide in colon epithelial cells by inhibition of
      basolateral K+ conductance.
AB  - BACKGROUND: The mechanism of the antisecretory effect of loperamide was
      investigated in cultured highly differentiated colon epithelial cells (HT-29/B6).
      METHODS: Chloride secretion was stimulated via cAMP by forskolin (FSK, 10(-5) M),
      via Ca2+ by the muscarinic agonist carbachol (CCh, 10(-4) M), and via protein
      kinase C by the phorbol ester PMA (5 x 10(-9) M). Stimulated Cl- secretion was
      quantified as short circuit current (I(SC)) of HT-29/B6 monolayers mounted in
      Ussing-type chambers. RESULTS: Loperamide (5 x 10(-5) M) inhibited I(SC)
      stimulated by FSK, CCh and PMA. The antisecretory action of loperamide was
      unaffected by preincubation with naloxone (10(-5) M). Furthermore, loperamide
      strongly inhibited basolateral 86Rb efflux. Like loperamide, the calmodulin
      antagonist trifluoperazine (10(-4) M) inhibited I(SC) induced by FSK, CCh or PMA.
      The Ca2+ channel blocker verapamil (5 x 10(-5) M), on the other hand, inhibited
      only PMA-stimulated I(SC),but had no effect on FSK or CCh-induced I(SC)
      CONCLUSIONS: Loperamide exerts a direct antisecretory action on chloride
      secretion of colon epithelial cells independently of the respective stimulatory
      signal transduction pathway. This antisecretory effect is not mediated by opiate
      receptors and reflects inhibition of basolateral K+ conductance.

PMID- 11444473
TI  - Differential expression of gastrin, cholecystokinin-A and cholecystokinin-B
      receptor mRNA in human pancreatic cancer cell lines.
AB  - BACKGROUND: It has been assumed that gastrin stimulates the growth of pancreatic
      cancer in an autocrine way through co-expression of gastrin and the
      cholecystokinin-B receptor (CCK-BR). However, pancreatic cancer cell lines
      established directly from patients have revealed a great heterogeneity in cell
      proliferation when exposed to CCK, gastrin and their receptor antagonists. The
      aim of this study was therefore to examine co-expression of CCK-A and CCK-B
      receptor (CCK-AR and CCK-BR), and gastrin mRNA as well as the secretion of CCK
      and gastrin peptides in these cell lines. METHODS: Fourteen cell lines were
      established from primary pancreatic cancers or their metastases. Total RNA was
      isolated from the cell lines and reverse-transcribed into single-stranded cDNA. A
      PCR technique based on Taq polymerase-antibody interaction and CCK-AR, CCK-BR and
      gastrin-specific primers, followed by Southern blot analysis, were the methods
      used. The incubation mediums were analysed for the presence of secreted
      CCK/proCCK and gastrin/progastrin peptides by specific radioimmunoassays (RIA).
      RESULTS: By means of nested Reverse-Transcribed Polymerase Chain Reaction (nested
      RT-PCR), combined with Southem blot analysis of the PCR amplified products, CCK
      AR and gastrin mRNA co-expression was detected in cell lines LPC-6p and LPC-10m,
      whereas CCK-BR and gastrin mRNA could be detected in cell lines LPC-8p and LPC
      12m. A low level of secreted CCK peptides was detected in cell line LPC-6p, which
      also expressed CCK-AR mRNA. In no other cases were CCK or gastrin peptides
      detected in the cell culture mediums. CONCLUSION: The lack of CCK-BR and gastrin
      mRNA co-expression, and not detectable levels of secreted CCK and gastrin in
      culture media, does not lend support to the hypothesis that concomitant gene
      expression of CCK receptors and gastrin or CCK are essential to maintaining
      pancreatic cancer cell proliferation.

PMID- 11444474
TI  - Effect of sodium butyrate on reactive oxygen species generation by human
      neutrophils.
AB  - BACKGROUND: Short-chain fatty acids enema has been shown to be effective in the
      treatment of ulcerative colitis (UC). However, the mechanisms that lead to this
      response have not been well characterized. The aims of this study were to
      investigate the effect sodium butyrate has on reactive oxygen species (ROS)
      generation by human neutrophils, which are responsible for mucosal injury.
      METHODS: Human neutrophils incubated with or without sodium butyrate were
      stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). ROS
      generation was largely differentiated with flow cytometry assays of hydroethidine
      oxidation and dichlorofluorescein oxidation for superoxide anion and hydrogen
      peroxide respectively, and luminol-dependent chemiluminescence for
      myeloperoxidase-mediated oxidants. RESULTS: Sodium butyrate (up to 50 mM) did not
      alter hydroethidine oxidation upon stimulation of the OZ or PMA. However, sodium
      butyrate at a concentration of 25 mM elevated dichlorofluorescein oxidation to
      125 + 8% (P = 0.028) of control upon stimulation of OZ and to 191 +/- 30% (P =
      0.0016) upon stimulation of PMA. Contrary to these results, sodium butyrate
      greatly inhibited chemiluminescence responses in a dose-dependent manner. The
      inhibition by 50 mM sodium butyrate was 61 +/- 6% upon OZ and 71 +/- 9% upon PMA,
      respectively. CONCLUSIONS: These data indicate that sodium butyrate up-regulates
      hydrogen peroxide generation but down-regulates generation of myeloperoxidase
      mediated oxidants, the latter being more potent in killing microorganisms and in
      inducing tissue injury. A possible mechanism is suggested whereby sodium butyrate
      may inhibit myeloperoxidase activity and hence attenuate the destructive
      activities of neutrophils in UC.

PMID- 11444475
TI  - Ulcerative colitis and colorectal carcinoma: DNA-profile, laminin-5 gamma2 chain
      and cyclin A expression as early markers for risk assessment.
AB  - BACKGROUND: Ulcerative colitis patients are at increased risk for developing
      colorectal carcinomas. Despite expensive surveillance programmes, clinical
      practice reflects an uncertainty in individual risk assessment. The aim of the
      study was to evaluate independent cellular features with possible predictive
      value. METHODS: Two patient groups were selected: group A comprised 8 patients
      with ulcerative colitis-associated colorectal carcinomas, group B comprised 16
      ulcerative colitis patients with risk factors (duration of disease, extent of
      inflammation, epithelial dysplasias). A total of 683 paraffin-embedded mucosal
      biopsies were retrospectively evaluated for inflammatory activity, grade of
      dysplasia, ploidy status, laminin-5 gamma2 chain and cyclin A expression.
      RESULTS: Mild or moderate inflammatory activity was present in 78% of all
      biopsies, low- or high-grade dysplasia in 5.5%. There was no difference in
      inflammatory activity and dysplasia between patient groups. In group A, 75% of
      the biopsies exhibited aneuploid DNA distribution patterns. Group B showed mainly
      proliferative-diploid cell populations (85% / P = 0.006). Laminin-5 gamma2 chain
      was expressed in 13% of all biopsies, with a higher frequency in group A (P =
      0.002). Cyclin A expression was found in 98% of all biopsies, with a higher
      number of immunopositive cells in group A biopsies (P = 0.014). CONCLUSIONS:
      Combined nuclear DNA assessment, laminin-5 gamma2 chain and cyclin A expression
      may help to identify ulcerative colitis patients with an increased risk for
      cancer development.

PMID- 11444476
TI  - Bone density reduction in patients with Crohn disease and associations with
      demographic and disease variables: cross-sectional data from a population-based
      study.
AB  - BACKGROUND: The extent of bone density reduction in patients with Crohn disease
      is still being debated. The aim of this study was to examine bone mineral density
      (BMD) and factors associated with reduced BMD in a representative population of
      patients with Crohn disease aged between 20 and 70 years. METHODS: BMD (using
      dual energy X-ray absorptiometry) was measured in spine and hip in 55 patients
      with Crohn disease recruited from the entire Crohn population (n = 96) in a
      defined area of southern Norway. Demographic and clinical data were also
      collected. The patients were compared with 52 age- and gender-matched healthy
      controls. Potential demographic and disease-related factors associated with BMD
      reduction were statistically tested with bi- and multivariate analyses. RESULTS:
      The BMD reduction in patients with Crohn disease was 7.1% (P = 0.02) in spine L1
      4, 6.1% (P = 0.08) in femoral neck and 8.4% (P = 0.02) in total hip as compared
      with the controls. In total hip and femoral neck, age, body weight and gender
      were independently associated with reduced BMD, but in the spine only body
      weight. Among the disease-related variables, only ever use of prednisolone was
      independently associated with reduction in BMD but this only in the femoral neck.
      CONCLUSIONS: The spine and hip BMD reduction of 6%-8% is similar to that found in
      a comparable population-based study performed in another area in Norway. Among
      the disease-related variables tested for, only the use of prednisolone was
      independently associated with BMD reduction. However, the BMD reduction measured
      in this study indicates that disease-related mechanisms are involved.

PMID- 11444477
TI  - Maternal susceptibility locus for obstetric cholestasis maps to chromosome region
      2p13 in Finnish patients.
AB  - BACKGROUND: Obstetric cholestasis, attributed to maternal hypersensitivity to
      estrogens, is a pregnancy-specific disorder characterized by pruritus and
      biochemical cholestasis in the second or third trimester of pregnancy. The
      pathophysiology of the disorder is incompletely understood, but the familial
      nature of the disease has long been recognized. Carriership of long-chain 3
      hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency has been reported to be
      associated with an increased risk of obstetric cholestasis and the gene is
      located in the p23 region of chromosome 2. METHODS: On the basis of this
      information, we conducted population-based linkage disequilibrium (LD) screening
      to find potential cholestasis-associated loci on chromosome 2. The study was
      carried out in 47 unrelated control women and in 45 cholestatic women, eight of
      whom had a positive family history. RESULTS: During initial screening with
      chromosome 2-specific microsatellite markers, the tetranucleotide marker D2S1394
      was found to be in LD in the 2p13 region. Screening this region with additional
      microsatellite markers revealed that the adjacent marker D2S1374 was also
      significantly associated with obstetric cholestasis, whereas no association was
      found with the markers located in the vicinity of the hydroxyacyl-CoA
      dehyrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit (HADHA)
      gene. CONCLUSIONS: Collectively, these data suggest that there may be a novel
      obstetric cholestasis-associated gene located in the vicinity of the 2p13 LD
      region.

PMID- 11444478
TI  - Faecal elastase-1: lyophilization of stool samples prevents false low results in
      diarrhoea.
AB  - BACKGROUND: In patients with diarrhoea, faecal elastase-1 is used to detect
      exocrine pancreatic insufficiency. Diarrhoea is defined as >85% stool water
      content. METHODS: We analysed elastase-1 in 519 stool samples from 310 patients
      unprocessed as well as after lyophilization in a standard laboratory
      lyophilizator. Stool water content was calculated by weight difference before and
      after lyophilization. RESULTS: 151 stool samples were classified as 'diarrhoea'
      (mean stool water content 88.8%); all others had a mean water content of 75.4%.
      In the 'diarrhoea' samples, elastase-1 levels were considerably higher after
      lyophilization--with a calculated normal water content of 75% (606 +/- 359
      microg/g, mean +/- s)--compared to measurement when unprocessed (279 +/- 151
      microg/g; P < 0.0001). In 16 of the 151 cases (11%), the abnormally low elastase
      1 level below 200 microg/g found in unprocessed stools proved normal (>200
      microg/g) after lyophilization and correction for stool water content.
      CONCLUSION: Diarrhoea can result in falsely decreased elastase-1 levels in a
      number of patients with non-pancreatogenic diarrhoea. Lyophilization is a simple
      measure by which to determine elastase-1 independently of stool water content.
      Lyophilization of stool samples can therefore help to prevent wrong positive
      elastase-1 test results.

PMID- 11444479
TI  - Economic burden of NSAID-induced gastropathy in Sweden.
AB  - BACKGROUND: Gastrointestinal side effects carry a significant cost related to the
      use of NSAID medications. METHODS: The economic burden of NSAID-induced gastric
      side effects is estimated using the cost-of-illness methodology. Costs are
      calculated using both a prevalence (top-down) approach and an incidence (bottom
      up) approach. RESULTS: Using the top-down approach, the total cost in 1998 of
      NSAID-induced ulcers was MSEK 329-586, direct costs accounting for 76%-83%. The
      bottom-up approach gives an estimate of MSEK 320, of which MSEK 290 was direct
      cost. About one-quarter of total costs for ulcer disease can be attributed to the
      use of NSAIDs. CONCLUSIONS: Gastrointestinal side effects carry a significant
      cost from the use of NSAIDs, costs that are as important as the price of NSAIDs.
      This should be considered when choice of drug and prophylaxis is being made.

PMID- 11444480
TI  - Idiosyncratic drug allergic phenprocoumon-induced hepatitis with subacute liver
      failure initially misdiagnosed as autoimmune hepatitis.
AB  - BACKGROUND: Coumarin anticoagulants are known to cause hepatotoxicity, but only a
      few cases have been reported. Coumarins are usually administered following
      cardiovascular surgery and the differential diagnosis is post-transfusion
      hepatitis. METHODS: We report the case of a 46-year-old woman who presented with
      jaundice, elevated liver function tests, positive antinuclear and smooth muscle
      antibodies following prodromal signs of fatigue and nausea. The patient had been
      treated with phenprocoumon for 5 months in order to prevent thromboembolism after
      two strokes assumed to be due to an open foramen ovale and an aneurysmatic atrial
      septum. RESULTS: There was no evidence of viral or other causes of hepatitis. The
      patient rapidly developed subacute liver failure with encephalopathy and
      phenprocoumon treatment was stopped. With intensive care support, as well as high
      dose prednisolone treatment, she recovered. Owing to positive antinuclear and
      smooth muscle antibodies, the initial diagnosis 'acute autoimmune hepatitis with
      liver failure was made. CONCLUSION: The lack of hypergammaglobulinaemia and the
      rapid recurrence of hepatitis following re-exposure to phenprocoumon led to the
      final diagnosis of phenprocoumon-induced idiosyncratic drug allergic hepatitis
      with secondary autoimmune phenomena.

PMID- 11444481
TI  - Pleural effusion as the initial manifestation of gastric adenocarcinoma: a report
      of four cases.

PMID- 11444482
TI  - Gender identity: a multidimensional analysis with implications for psychosocial
      adjustment.
AB  - This study examined the relations between components of gender identity and
      psychosocial adjustment. The aspects of gender identity assessed were (a)
      feelings of psychological compatibility with one's gender (i.e.. feeling one is a
      typical member of one's sex and feeling content with one's biological sex), (b)
      feelings of pressure from parents, peers, and self for conformity to gender
      stereotypes. and (c) the sentiment that one's own sex is superior to the other
      (intergroup bias). Adjustment was assessed in terms of self-esteem and peer
      acceptance. Participants were 182 children in Grades 4 through 8. Felt gender
      compatibility (when operationalized as either self-perceived gender typicality or
      feelings of contentment with one's biological sex) was positively related to
      adjustment, whereas felt pressure and intergroup bias were negatively associated
      with adjustment. The results provide new insights into the role of gender
      identity in children's well-being, help identify sources of confusion in previous
      work, and suggest directions for future inquiry.

PMID- 11444483
TI  - When girls versus boys play alone: nonsocial play and adjustment in kindergarten.
AB  - The goal of the present study was to examine the relations between different
      forms of children's nonsocial play behaviors and adjustment in kindergarten. The
      participants in this study were 77 kindergarten children (38 boys, 39 girls; mean
      age = 66.16 months, SD = 4.11 months). Mothers completed ratings of child shyness
      and emotion dysregulation. Children's nonsocial play behaviors (reticent,
      solitary-passive. solitary active) were observed during free play. In addition,
      teachers rated child behavior problems (internalizing and externalizing) and
      social competence; academic achievement was assessed through child interviews.
      Results from regression analyses revealed that different types of nonsocial play
      were differentially associated with child characteristics and indices of
      adjustment. For some forms of nonsocial play, the nature of these associations
      differed significantly for boys and girls.

PMID- 11444484
TI  - Mothers' emotional expressivity and children's behavior problems and social
      competence: mediation through children's regulation.
AB  - The relations between mothers' expressed positive and negative emotion and 55-79
      month-olds' (76% European American) regulation, social competence, and adjustment
      were examined. Structural equation modeling was used to test the plausibility of
      the hypothesis that the effects of maternal expression of emotion on children's
      adjustment and social competence are mediated through children's dispositional
      regulation. Mothers' expressed emotions were assessed during interactions with
      their children and with maternal reports of emotions expressed in the family.
      Children's regulation, externalizing and internalizing problems. and social
      competence were rated by parents and teachers, and children's persistence was
      surreptitiously observed. There were unique effects of positive and negative
      maternal expressed emotion on children's regulation. and the relations of
      maternal expressed emotion to children's externalizing problem behaviors and
      social competence were mediated through children's regulation. Alternative models
      of causation were tested; a child-directed model in which maternal expressivity
      mediated the effects of child regulation on child outcomes did not fit the data
      as well.

PMID- 11444485
TI  - Getting older, getting better? Personal strivings and psychological maturity
      across the life span.
AB  - Measures of psychological maturity based on personal strivings (R. A. Emmons,
      1989) were administered to 108 adults aged 17-82. On the basis of organismic
      theoretical assumptions regarding maturity, age was hypothesized to be positively
      associated with K. M. Sheldon and T. Kasser's (1995, 1998) two goal-based
      measures of personality integration. E. Erikson's (1963) assumptions regarding
      maturity were the basis for the hypothesis that older people would tend to list
      more strivings concerning generativity and ego integrity and fewer strivings
      concerning identity and intimacy. Finally, on the basis of past research
      findings, maturity and age were hypothesized to be positively associated with
      subjective well-being. Results supported these hypotheses and also showed that
      measured maturity mediated the relationship between age and well-being. Thus,
      older individuals may indeed be more psychologically mature than younger people
      and may be happier as a result.

PMID- 11444486
TI  - Marital behavior, parenting behavior, and multiple reports of preschoolers'
      behavior problems: mediation or moderation?
AB  - Associations among positive and conflictual marital behavior and multiple reports
      of child behavior problems were examined in a community sample of 78 families
      with 3-year-old children. Maternal and paternal parenting behaviors were tested
      as potential mediators and moderators. Parents reported on child behavior
      problems and were observed during parent-child interaction and couple discussion
      in the presence of the child. Observers and preschool teachers also reported on
      child behavior problems. Less positive marital engagement and greater conflict
      were associated with observers' reports, but not with parents' or teachers'
      reports, of more behavior problems. Associations between marital behavior and
      child behavior problems were not explained by maternal or paternal behavior;
      stronger support was found for moderating effects of parenting. Also, positive
      marital engagement was a slightly better predictor of child behavior problems
      than was marital conflict.

PMID- 11444487
TI  - Correlates of victimization in Chinese children's peer groups.
AB  - This study reports a cross-sectional investigation of the behavioral and academic
      correlates of victimization in Chinese children's peer groups. The participants
      were 296 children (161 boys and 135 girls; mean age = 11.5 years) from Tianjin,
      China. Multi-informant assessments (peer nominations, teacher ratings, and self
      reports) of peer victimization, aggression, submissiveness-withdrawal,
      assertiveness-prosociability, and academic functioning were obtained. Structural
      equation models indicated that peer victimization was associated with poor
      academic functioning, submissive-withdrawn behavior, aggression, and low levels
      of assertive-prosocial behavior. These findings suggest that there is
      considerable similarity in the social processes underlying peer group
      victimization across Chinese and Western cultural settings.

PMID- 11444488
TI  - Infant temperament and the brainstem auditory evoked response in later childhood.
AB  - Brainstem auditory evoked responses (BAERs) were evaluated on 10-12-year-old
      children (N = 56) who had been classified as high or low reactive to unfamiliar
      stimuli at 4 months of age. BAER measurement was selected because high reactive
      infants tend to become inhibited or fearful young children, and adult introverts
      have a faster latency to wave V of the BAER than do extroverts. Children
      previously classified as high reactive at 4 months had larger wave V components
      than did low reactive children, a finding that possibly suggests greater
      excitability in projections to the inferior colliculus. The fact that a
      fundamental feature of brainstem activity differentiated preadolescent children
      belonging to two early temperamental groups supports the value of gathering
      physiological data in temperament research.

PMID- 11444489
TI  - Visual short-term memory in the first year of life: capacity and recency effects.
AB  - A span task was developed to assess the amount of information infants could hold
      in short-term memory. In this task, infants were presented with up to 4 items in
      succession and then tested for recognition by successively pairing each item with
      a novel one. A large sample of full-terms and low-birth-weight preterms (< 1,750
      g) was tested longitudinally, at 5, 7, and 12 months of age. Results were similar
      for both groups: (a) Longer spans were more difficult, especially at the 2
      younger ages; (b) memory capacity increased over the 1st year of life--whereas
      less than 25% of the sample could hold as many as 3-4 items in mind at once at
      the younger ages, nearly half could do so by 12 months of age; (c) there was a
      marked recency effect (greater memory for the final item) for spans of 3 and 4 at
      all ages; and (d) there were modest cross-age correlations, indicating that
      individual differences in memory capacity showed some stability from age to age.

PMID- 11444490
TI  - Peer rejection as an antecedent of young children's school adjustment: an
      examination of mediating processes.
AB  - A short-term longitudinal design (N = 399) was used to examine peer relations
      processes that may mediate the relation between peer rejection and children's
      emotional and academic adjustment during kindergarten. These proposed mediating
      processes extend the current literature by explicating behavioral pathways via
      which the attitudinal construct of peer rejection may affect adjustment outcomes.
      Structural equatiton modeling results supported the hypothesis that negative peer
      treatment (e.g., victimization, refusal of peer group entry bids, and exclusion
      from peer activities) and classroom participation partially mediate the
      relationship between rejection and adjustment outcomes. Rejected children were
      more likely to experience negative peer treatment, more likely to show decreases
      in classroom participation, and more likely to report loneliness, to express a
      desire to avoid school, and to perform less well on achievement measures.

PMID- 11444491
TI  - The development of reaching and looking preferences in infants to objects of
      different sizes.
AB  - Reaching and looking preferences and movement kinematics were recorded in 5-15
      month-old infants, who were divided into 3 age groups. Infants were presented
      with pairs of cylinders of 3 different diameters: small (1-cm diameter), medium
      (2.5-cm diameter), and large (6-cm diameter). Whereas infants between 5 and 12
      months of age showed a preference for looking first at the large object, a
      significant preference for reaching to smaller (graspable) objects was observed
      in 81/2-12-month-old infants. Kinematic measures suggest that the onset of object
      oriented action requires a slowing down of the reach and an extended "homing-in"
      phase. The divergent looking and reaching preferences in infants at different
      ages may reflect a dissociation during development of visual processing streams
      subserving object-related action from those related to visual orienting.

PMID- 11444492
TI  - Influence of atenolol on the kinetics of RT interval rate adaptation in conscious
      dogs.
AB  - The objective was to test an effect of atenolol independent of heart rate on
      electrocardiographic RT rate adaptation by investigating RT adaptation during
      spontaneous rate and after an abrupt change of atrial rate (study of RT delay).
      Digital electrocardiograms were recorded from eight conscious dogs. Analysis of
      RT interval (measured from QRS apex to end of T) was performed on a beat-to-beat
      basis. The protocol was repeated in the control state and after atenolol
      administration (2 mg/kg). Regarding spontaneous heart rate, an increased or
      decreased RR duration did not modify the beat-to-beat relative adaptation of RT
      to a change of RR (2.15 +/- 1% during control). Atenolol increased mean RR (p <
      0.001) and decreased relative adaptation of RT (0.22 +/- 0.18%, p < 0.001). The
      inverse correlation between mean RR and the relative RT adaptation (r = -0.76, p
      < 0.05) disappeared after atenolol administration. Regarding RT delay, complete
      adaptation of RT required 3 min; 48 +/- 16% of this adaptation was observed after
      the first beat and 60 +/- 11% was observed after the 20th. Atenolol attenuated
      this adaptation during the first six beats following the abrupt cycle length
      change (p < 0.05). We concluded that the attenuation of RT rate adaptation after
      atenolol is related to heart rate modulation and to the time delay in RT rate
      adaptation.

PMID- 11444493
TI  - Protease-activated receptor (PAR) 1 but not PAR2 or PAR4 mediates endothelium
      dependent relaxation to thrombin and trypsin in human pulmonary arteries.
AB  - Endothelial protease-activated receptors (PARs) may be important sensors of
      vascular inflammation and injury. Activation of endothelial PAR1 and PAR2 causes
      nitric oxide-mediated arterial smooth muscle relaxation in a number of species
      and PAR4 activation causes similar responses in isolated rat aorta. However, it
      is unclear whether these receptors mediate such responses in human arteries
      because the most potent activators of PAR1, PAR2, and PAR4, thrombin and trypsin,
      cause endothelium-dependent relaxation of human coronary arteries through a
      common PAR1-like receptor. This study aimed to determine whether this unique
      pharmacology of PARs in human coronary arteries extends to human pulmonary
      arteries. PAR1 and PAR2 mRNA and protein were detected in human pulmonary
      arteries via reverse transcription polymerase chain reaction and
      immunohistochemistry, respectively. PAR4 mRNA was also detected in human
      pulmonary arteries. Contracted human pulmonary artery ring segments suspended for
      isometric tension measurement relaxed in a concentration- and endothelium
      dependent manner to thrombin (0.001-0.1 U/ml), trypsin (0.01-1 U/ml), and the
      PAR1-activating peptide, SFLLRN (0.1-10 microM). By contrast, the PAR2- and PAR4
      activating peptides, SLIGKV and GYPGQV, respectively, caused neither contraction
      nor relaxation of precontracted human pulmonary arteries. Relaxations to thrombin
      and trypsin cross-desensitized, while tachyphylaxis to SFLLRN abolished
      subsequent relaxations to both thrombin and trypsin. We conclude that human
      pulmonary arteries express PAR1, PAR2, and PAR4, but that only PAR1, or a PAR1
      like receptor, is coupled to endothelium-dependent relaxation.

PMID- 11444494
TI  - Effects of polychlorinated biphenyl 19 (2,2',6-trichlorobiphenyl) on contraction,
      Ca2+ transient, and Ca2+ current of cardiac myocytes.
AB  - Polychlorinated biphenyls (PCBs) have been known as serious environmental
      pollutants, causing developmental delays, motor dysfunction, and decrease in
      brain dopamine level in humans and animals. We have investigated the effects of a
      PCB congener, 2,2',6-trichlorobiphenyl (PCB 19) on contractile force, Ca2+
      transient, and L-type Ca2+ current (I(Ca,L)) in guinea pig ventricular myocytes
      stimulated at a rate of 0.25-0.33 Hz. PCB 19 decreased contractile force in a
      concentration-dependent manner. During the negative inotropic response, the
      action potential duration at 20% (APD20), 90% of repolarization (APD90), and the
      action potential amplitude (APA) were decreased concentration dependently: 30
      microM PCB 19 reduced APD20, APD90 and APA by 36.7 +/- 3.5%, 22.6 +/- 3.9%, and
      2.4 +/- 0.6%, respectively (n = 11, p < 0.01). PCB 19 30 microM decreased the
      Ca2+ transient and the I(Ca,L) by 46.8 +/- 1.8% (n = 9, p < 0.01) and 47.1 +/-
      3.1% (n = 9, p < 0.01), respectively. The results suggest that PCB 19 decreased
      the Ca2+ transient through inhibition of L-type Ca2+ channels and that the
      decreased Ca2+ transient consequently caused a negative inotropic effect in
      cardiac myocytes.

PMID- 11444495
TI  - Analysis of vasodilator responses to novel nitric oxide donors in the
      hindquarters vascular bed of the cat.
AB  - Controlled release of nitric oxide (NO*) may be useful in the treatment of a
      variety of vascular disorders. NO* donors of the diazeniumdiolate family with
      different rates of spontaneous NO* release have been synthesized. In the current
      study responses to seven diazeniumdiolate NO* donors (DEA/NO*, DETA/NO*, OXI/NO*,
      PIPERAZI/NO*, PROLI/NO*, SPER/NO*, and SULFI/NO*) were investigated in the
      hindquarters vascular bed of the cat. Intravenous injections of all NO* donors
      caused dose-dependent decreases in systemic arterial pressure and the rank order
      of potency was SNP > DEA/NO* > PIPERAZI/NO* > SPER/NO* > PROLI/NO* > OXI/NO*.
      Injections of all NO* donors into the hindlimb perfusion circuit caused dose
      related decreases in hindquarters perfusion pressure that were similar to the
      order of potency in decreasing systemic arterial pressure. The rank order of the
      time required for the response to return to 50% of the maximal decrease in
      pressure (T(1/2)) and total duration of action of the NO* donors was SPER/NO* >
      PIPERAZI/NO* > DEA/NO* > OXI/NO* > DETA/NO* > PROLI/NO* > SULFI/NO*. After
      treatment with the NO* synthase inhibitor, N(omega)-nitro-L-arginine methyl ester
      (100 mg/kg, i.v.), hindlimb vasodilator responses to the NO* donors were not
      significantly different, but vasodilator responses to acetylcholine were
      significantly reduced. After treatment with zaprinast (2 mg/kg, i.v.), a type V
      cyclic 3',5'-guanosine monophosphate-specific phosphodiesterase inhibitor, the
      duration of vasodilator responses to the NO* donors, as measured by T(1/2), was
      increased significantly, whereas the duration of the response to the beta2
      adrenergic receptor agonist albuterol was unchanged. These data suggest that
      diazeniumdiolate NO* donors are endothelium-independent, directly stimulate
      soluble guanylate cyclase, and decrease vascular resistance by increasing cyclic
      3',5'-guanosine monophosphate levels in the hindquarters vascular bed of the cat.

PMID- 11444496
TI  - Effects of SK&F 96365 and mefenamic acid on Ca2+ influx in stimulated endothelial
      cells and on endothelium-derived hyperpolarizing factor-mediated arterial
      hyperpolarization and relaxation.
AB  - This study was undertaken to assess how Ca2+ influx into endothelial cells via
      Ca2+-permeable nonselective cation channels (NSCCs) is important in vascular
      responses mediated by endothelium-derived hyperpolarizing factor (EDHF). In
      cultured porcine aortic endothelial cells, the sustained increases in the
      intracellular Ca2+ concentration ([Ca2+]i) elicited by bradykinin and
      cyclopiazonic acid, which were strongly dependent on the presence of
      extracellular Ca2+, were suppressed by the NSCC blockers, SK&F 96365 and
      mefenamic acid. In porcine coronary artery with intact endothelium, bradykinin
      elicited a rapid fall in the membrane potential, followed by sustained
      hyperpolarization with a slow decay. In the presence of SK&F 96365 or mefenamic
      acid, the peak amplitude was severely reduced and the decay phase of
      hyperpolarization to bradykinin was greatly accelerated, which was apparently
      similar to the response obtained in Ca2+-free medium. Cyclopiazonic acid caused
      sustained hyperpolarization in an extracellular Ca2+-dependent manner, an effect
      which was markedly diminished by SK&F 96365 and mefenamic acid. In rings of
      coronary artery precontracted with U46619, bradykinin and cyclopiazonic acid
      produced endothelium-dependent relaxations even in the presence of N(G)-nitro-L
      arginine and indomethacin. SK&F 96365 and mefenamic acid significantly attenuated
      the relaxant responses. These results indicate that the increase in [Ca2+]i of
      endothelial cells due to Ca2+ entry via NSCCs plays a crucial role in the
      maintenance of the EDHF-mediated vascular responses.

PMID- 11444497
TI  - Effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on
      angiotensin II-induced facilitation of sympathetic neurotransmission in the rat
      mesenteric artery.
AB  - SUMMARY: The effect of the AT1-receptor antagonists losartan, irbesartan, and
      telmisartan on angiotensin II (Ang II)-induced facilitation of noradrenergic
      neurotransmission was investigated in the isolated rat mesenteric artery under
      isometric conditions. Electrical field stimulation (2, 4, and 8 Hz) caused a
      frequency-dependent increase of contractile force. At stimulation frequencies of
      2, 4, and 8 Hz, Ang 11 (10 nM) increased the stimulation-induced vasoconstrictor
      responses by a factor 4.8 +/- 0.9, 2.9 +/- 0.7, and 1.3 +/- 0.1, respectively (p
      < 0.05 compared with control for all frequencies). The enhancement could be
      concentration-dependently antagonized by losartan (1 nM-1 microM), irbesartan
      (0.1 nM-0.1 microM), and telmisartan (0.01 nM-0.01 microM). At a stimulation
      frequency of 2 Hz, the relation between stimulation-induced vasoconstrictor
      responses (in presence of Ang II 10 nM) and the concentration of the AT1
      antagonists used could be described by linear regression. The order of potency
      concerning sympathoinhibition was telmisartan > irbesartan > losartan (p < 0.05
      between linear regression lines). Contractile responses to exogenous
      noradrenaline were unaltered in the presence of Ang II 10 nM. We conclude that
      the facilitating effect of Ang II on noradrenergic neurotransmission is mediated
      by presynaptically located AT1-receptors. Conversely, this facilitating effect
      can be dose-dependently counteracted by blockade of these receptors.
      Sympathoinhibitory properties are likely to contribute to the therapeutic effect
      of AT1-blockers, in particular in conditions in which the sympathetic nervous
      system is activated, such as congestive heart failure and hypertension.

PMID- 11444498
TI  - Potentiation of sildenafil-induced hypotension is minimal with nitrates
      generating a radical intermediate.
AB  - Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced
      into therapy for erectile dysfunction. Because of the phosphodiesterase-5
      inhibitor-induced increases of cyclic GMP in the vasculature, vasodilation in
      various vascular beds is induced, which in combination with various
      nitrovasodilators (e.g., when used simultaneously for the treatment of coronary
      artery disease), may lead to excessive hypotension. Thus nitrovasodilators are
      contraindicated when sildenafil may be used and reports of a number of accidents
      have recently been published. We therefore studied the acute interactions of
      glyceryl trinitrate (GTN), pentaerythritol tetranitrate (PETN), and isosorbide
      dinitrate (ISDN) with sildenafil in six chronically instrumented conscious dogs
      for each nitrate to assess the magnitude of blood pressure drops (and
      compensatory increases in heart rate) during a 24-h nitrate administration
      (infusion into the pulmonary artery). Sildenafil (3 mg/kg) was given orally
      (after a 24-h fast) 30 min after start of nitrate infusion. GTN, PETN, or ISDN
      (which follow different steps of metabolic conversion to nitric oxide) were
      applied at submaximal dosages leading to 90% of maximal coronary artery dilation
      at 1.5 microg/kg per min, 0.75 microg/kg per min, or 6 microg/kg per min,
      respectively. During GTN infusion sildenafil caused a maximum drop in mean blood
      pressure of 21 +/- 3 mm Hg (rise in heart rate from 117.0 +/- 7.2 to 126.0 +/- 6
      .0/min) and during ISDN infusion of 18 +/- 3 mm Hg (rise in heart rate from 115.0
      +/- 7.0 to 125 +/- 6/min), which was significantly less (p < 0.01) during PETN
      (only 6 +/- 1 mm Hg with a rise in heart rate from 107.0 +/- 5.0 to 122.0 +/-
      7.0/min). When sildenafil is used during exposure to nitrates (e.g., in coronary
      artery disease), the PETN-induced drop in blood pressure at equi-effective
      dosages (with regard to coronary dilation) is substantially smaller compared with
      that of GTN or ISDN, which is probably because of lesser potentiation of
      phosphodiesterase-5 inhibitor-induced effects in the arteriolar bed, thus
      minimizing critical drops in blood pressure.

PMID- 11444499
TI  - Controlled nicorandil administration for myocardial protection during coronary
      artery bypass grafting under cardiopulmonary bypass.
AB  - Nicorandil is a hybrid potassium channel opener, and recent experimental studies
      have demonstrated its efficacy in myocardial protection against ischemia
      reperfusion. This clinical study was designed to examine the myocardial
      protective effect of nicorandil administered during cardiopulmonary bypass.
      Seventy adult patients, 53 men and 17 women, undergoing elective coronary artery
      bypass grafting were randomly assigned to two groups, one receiving nicorandil
      during cardiopulmonary bypass (group N, n = 35) and the other receiving no
      nicorandil for control (group C, n = 35). Nicorandil was administered at each
      dose of 0.1 mg/kg into the cardiopulmonary bypass circuit according to the
      following schedule: (1) bolus injection at the initiation of cardiopulmonary
      bypass, (2) continuous infusion for 5 min before aortic cross-clamping, (3) bolus
      administration at 5 min before reperfusion, and (4) continuous infusion for 5 min
      before reperfusion. The time required for achieving cardiac arrest after the
      initial cardioplegia was significantly reduced in group N in comparison with that
      in group C. After aortic unclamping, the number of patients showing a significant
      ST segment change on the electrocardiogram was significantly fewer in group N,
      whereas the number of patients showing spontaneous recovery of heart beat was
      significantly greater. As for the myocardial protective effect, group N showed
      lower plasma levels of malondialdehyde, human-heart fatty acid-binding protein,
      and peak creatine kinase-MB, and required lower doses of catecholamine. Our
      results suggest that nicorandil administration during cardiopulmonary bypass
      provides enhanced myocardial protective effects against ischemia-reperfusion in
      patients undergoing coronary artery bypass grafting.

PMID- 11444500
TI  - Nonselective endothelin receptor antagonist initiated soon after the onset of
      myocardial infarction may deteriorate 24-hour survival.
AB  - To investigate the effects of endothelin blockade initiated immediately after the
      onset of myocardial infarction on survival and left ventricular remodeling,
      treatment with the nonselective receptor antagonist TAK-044 (n = 22) or saline (n
      = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The
      24-h survival rate was significantly lower in the TAK-044 group than in the
      saline group. The systolic blood pressure 24 h after the onset of myocardial
      infarction was similar in the saline and TAK-044 groups, although it was
      significantly lower in the TAK-044 group during the 3-week protocol. Heart
      weight/tibial length was significantly increased in the TAK-044 group compared
      with the saline group. As all deaths in the TAK-044 group occurred within 24 h
      after myocardial infarction, we performed additional experiments using a separate
      group of rats 12-16 h after myocardial infarction. Plasma and myocardial
      endothelin-1 levels were significantly increased, and a bolus injection of TAK
      044 significantly reduced left ventricular dP/dtmax in these rats that had had a
      myocardial infarction compared with sham-operated rats. Endothelin receptor
      blockade initiated immediately after the onset of myocardial infarction may
      deteriorate acute-phase survival and left ventricular remodeling. Inhibition of
      the positive inotropic action of endothlin-1 may partially explain the increased
      24-h mortality.

PMID- 11444501
TI  - Effect of telmisartan on angiotensin II-mediated collagen gel contraction by
      adult rat cardiac fibroblasts.
AB  - The possible contributions of the angiotensin receptor subtypes 1 and 2 on the
      angiotensin II-induced collagen gel contraction by adult rat cardiac fibroblasts
      were studied using the specific angiotensin receptor type 1 and 2 antagonists
      telmisartan and P-186, respectively. Cardiac fibroblasts (from normal male adult
      rats) from passage 2 were cultured to confluency and added to a hydrated collagen
      gel, with or without angiotensin II, angiotensin II plus telmisartan, or
      angiotensin II plus P-186 in Dulbecco's Modified Eagle's Medium containing 5%
      fetal bovine serum for 1, 2, or 3 days. Control gels containing adult rat cardiac
      fibroblasts showed a significant amount of contraction after 3 days of
      incubation, causing a contraction to 67.9 +/- 7.1% of the area after 1 day.
      Angiotensin II (10(-7) M) stimulated (p < or = 0.05) the contraction of collagen
      mediated by cardiac fibroblasts after 1, 2, or 3 days. Telmisartan (10(-7) M)
      completely blocked the angiotensin II-induced collagen contraction by cardiac
      fibroblasts. P-186 (10(-7) M) had no effect on the angiotensin II-induced
      collagen contraction by cardiac fibroblasts. Addition of telmisartan and P-186
      alone did not affect the collagen gel contraction by cardiac fibroblasts. Our
      data demonstrate that the effects of angiotensin II on the collagen gel
      contraction by adult rat cardiac fibroblasts are angiotensin II type 1 receptor
      mediated because they were abolished by the specific angiotensin II type 1
      receptor antagonist telmisartan but not by the specific angiotensin II type 2
      receptor antagonist P-186.

PMID- 11444502
TI  - Oxidative stress increases endothelin-1 synthesis in human coronary artery smooth
      muscle cells.
AB  - Endothelins, nitric oxide, and oxygen-derived free radicals decisively regulate
      vascular tone. An imbalance in the biosynthesis of these substances in
      pathophysiologic conditions may trigger vasospasm and promote the development of
      atherosclerosis. Previous studies have shown that oxygen-derived free radicals
      can increase the synthesis of endothelin-1 in cultured endothelial cells.
      Interestingly, conditions of increased oxidative stress within smooth muscle
      cells as induced by angiotensin II infusion or hypercholesterolemia have been
      shown to be associated with increased autocrine synthesis of endothelin-1.
      Because endothelin-1 formed in smooth muscle cells can trigger hypersensitivity
      to vasoconstrictors, we tested whether oxidative stress per se may affect
      endothelin expression in vascular smooth muscle cells. Cultured human coronary
      artery smooth muscle cells were exposed to oxidative stress generated by the
      xanthine/xanthine oxidase reaction or by hydrogen peroxide. Preproendothelin-1
      mRNA content was quantitated by means of quantitative polymerase chain reaction
      and endothelin-1 protein was measured by radioimmunoassay. Incubation with
      xanthine/xanthine oxidase significantly increased preproendothelin-1 mRNA
      synthesis, whereas GAPDH remained unchanged. Likewise, xanthine/xanthine oxidase
      also led to a dose-dependent increase of intracellular endothelin-1. The increase
      in ET-1 expression induced by xanthine/xanthine oxidase was significantly
      inhibited by superoxide dismutase but not by catalase. We conclude that oxygen
      derived free radicals can stimulate the synthesis of endothelin-1 in endothelial
      and vascular smooth muscle cells by increasing preproendothelin-1 mRNA content
      and that this effect is mediated predominantly by superoxide anions. We therefore
      have identified a new mechanism in the interaction of oxidative stress and
      endothelin-1 expression in smooth muscle cells that may have important
      implications in diseases such as atherosclerosis and hypertension.

PMID- 11444503
TI  - Presynaptic regulation of cardiac norepinephrine release in ischemia.
AB  - In myocardial ischemia presynaptic regulation of norepinephrine release may be
      altered either by ischemic effects on presynaptic receptor signaling or by
      ischemia-evoked accumulation of endogenous agonists. Because presynaptic
      receptors are targets of several drugs. such alterations may have
      pharmacotherapeutic implications. We investigated the effect of brief ischemic
      periods on presynaptic regulation of norepinephrine release by alpha2
      adrenoceptors, beta2-adrenoceptors, adenosine A1-, angiotensin AT1-, and
      bradykinin B2-receptors in isolated perfused rat hearts. Exocytotic
      norepinephrine release was evoked by electrical field stimulation. Paired
      stimulations were performed to compare the pharmacologic intervention (S2) with
      the release under baseline conditions (S1), and the effects of receptor agonists
      and antagonists were compared under nonischemic and stop-flow conditions. In
      summary. during brief myocardial ischemia, presynaptic modulation of
      norepinephrine release is differentially regulated. Autoinhibitory alpha2
      adrenoceptors lose their activity, whereas stimulatory beta2-adrenoceptors are
      sensitized. Inhibitory adenosine A1-receptors gain importance during ischemia
      owing to endogenous adenosine formation. Bradykinin- and angiotensin-mediated
      stimulation of norepinephrine release is not affected under ischemic conditions.

PMID- 11444504
TI  - Lipophilic statins augment inducible nitric oxide synthase expression in cytokine
      stimulated cardiac myocytes.
AB  - Nitric oxide production by inducible nitric oxide synthase (iNOS) may play an
      important role in the pathogenesis of cardiovascular dysfunction. We investigated
      the effects of statins on iNOS expression and subsequent nitric oxide synthesis
      in cardiac myocytes and the mechanism by which statins exert their effects. We
      measured the production of nitrite, a stable metabolite of nitric oxide, in
      cultured neonatal rat cardiac myocytes with the Griess reagent. iNOS mRNA and
      protein expression were assayed by reverse transcription polymerase chain
      reaction and Western blotting, respectively. The lipophilic statins fluvastatin
      and lovastatin significantly increased interleukin-1beta-induced nitrite
      production by cardiac myocytes, whereas hydrophilic pravastatin did not.
      Increased nitrite production by fluvastatin was accompanied by increased iNOS
      mRNA and protein accumulation. Exogenous mevalonate, but not squalene,
      significantly blocked the stimulatory effect of fluvastatin on nitrite
      production. Cotreatment with geranylgeranyl-pyrophosphate also reversed the
      effect of fluvastatin. Furthermore, both Rho inhibitor C3 exoenzyme and Rho
      kinase inhibitor Y-27632 significantly increased interleukin-1beta-induced
      nitrite accumulation in cardiac myocytes. These results demonstrated that
      lipophilic statins upregulate iNOS expression and subsequent nitric oxide
      formation in cardiac myocytes via inhibition of Rho.

PMID- 11444505
TI  - Effect of repeated regional myocardial ischemia in the rat heart on reperfusion
      arrhythmias and release of norepinephrine.
AB  - We tested the hypothesis that repetitive regional myocardial ischemia in the rat
      could decrease reperfusion ventricular arrhythmias, possibly acting by diminished
      release of norepinephrine. Isolated perfused working rat hearts were pre-labeled
      with tritiated norepinephrine (NE3H). The efflux of 3H-labeled compounds was
      measured in the effluent coronary flow. Each heart was subjected to two
      consecutive periods of regional myocardial ischemia induced by ligature of the
      left coronary artery. The duration of the first ischemic period was 5 or 10 min
      and that of the second was 10 min. Serious rhythm disturbances did not occur
      during the first period of ischemia but did after reperfusion. The amount of NE3H
      liberated during the reperfusion period was more marked after an initial ischemic
      period of 10 min than after 5 min of ischemia. Reperfusion arrhythmias were of
      little importance after 5 min of ischemia but developed in a sustained pattern
      when reperfusion followed 10 min of ischemia. After 5 min of ischemia, the mean
      duration of reperfusion arrhythmias was 12.8 +/- 10.4 s during the first 3 min of
      reperfusion, but after 10 min of ischemia the mean duration of serious rhythm
      disturbances was 149.7 +/- 16.7 s. Reperfusion after the second 10-min occlusion
      increased the release of NE3H. In series 5-10, the percentage of NE3H compared
      with the total radioactivity was a mean of 71.4 +/- 3.3% during the 5 min of
      ligature, 79.0 +/- 5.3% during the first 3 min of reperfusion. During the 10-10
      series in which the ligature was maintained for 10 min, the percentage of NE3H
      compared with the total radioactivity was 70.6 +/- 5.1%, 81.1 +/- 8.7% during the
      first 3 min of reperfusion. These results show no reduction of any catecholamine
      release or of reperfusion arrhythmias by repetitive regional ischemia and provide
      no evidence for any preconditioning effect after short periods of regional
      ischemia. The antiarrhythmic effects of repetitive myocardial ischemia such as
      preconditioning previously reported may depend on the exact protocols used.

PMID- 11444506
TI  - Influence of nitric oxide synthase inhibition and endothelin-1 receptor blockade
      on acetylcholine-induced coronary artery contraction in vitro in dilated and
      ischemic cardiomyopathies.
AB  - The normal dilatory response to acetylcholine (ACH) is reduced in coronary
      vessels from patients with dilated cardiomyopathy (DCM) and reversed to a
      contraction in patients with coronary artery disease (CAD) and ischemic
      cardiomyopathy (ICM). This study investigated the influence of nitric oxide
      synthase inhibition and endothelin (ET)-1 receptor blockade on the reactivity to
      ACH of coronary arteries isolated from patients with end-stage congestive heart
      failure (CHF) associated or not with CAD. Small (approximately 400 microm)
      epicardial right coronary arteries were isolated from explanted hearts of
      patients undergoing transplantation for DCM or ICM. Segments were mounted on a
      wire myograph to record changes in isometric tension. ACH (1 microM) dilated pre
      contracted vessels from DCM hearts but contracted pre-contracted vessels from ICM
      hearts. In the absence of pre-contraction, ACH (10(-9)-3 x 10(-5) M) induced a
      small contraction of rings from DCM hearts and a larger contraction (p < 0.05) of
      rings from ICM hearts. N(omega)-nitro-L-arginine (L-NNA, 100 microM), a NO
      synthase inhibitor, increased (p < 0.05) sensitivity and maximal response to ACH
      of vessels from DCM hearts only. In the presence of L-NNA, blockade of ET(A) with
      BQ123 (1 microM) prevented the effects of L-NNA in DCM, whereas blockade of
      ET(A/B) receptors with bosentan (10 microM) only reduced vascular sensitivity to
      ACH without significantly reducing the maximal contraction to ACH in DCM. The
      antagonists had no effects in vessels from ICM hearts. ACH, however, induced
      similar contractions of vessels without endothelium in DCM and ICM. These results
      suggest that ACH induces a contraction by stimulating smooth muscle muscarinic
      receptors. In coronary arteries isolated from DCM hearts, the contraction is
      regulated by NO and ET-1, whereas these factors seem to have little influence in
      ICM. This suggests that endothelial muscarinic receptors are either not expressed
      or uncoupled in ICM hearts.

PMID- 11444507
TI  - The kidney in congestive heart failure: renal adverse event rate of treatment.
AB  - In this paper we review the effect of medical treatment on renal function in
      patients with congestive heart failure. We have examined data from the large
      scale heart failure studies with angiotensin-converting enzyme inhibitors,
      angiotensin receptor blockers, calcium channel blockers, beta-receptor blockers,
      an aldosterone antagonist, and a vasopeptidase inhibitor. Renal outcome was
      reported in almost all of the studies with angiotensin-converting enzyme
      inhibitors. Despite concern about renal adverse events with drugs in this class,
      they seem to be safe in patients with congestive heart failure. In contrast, we
      did not find any report about renal function in patients treated with beta
      receptor blockers for congestive heart failure.

PMID- 11444508
TI  - Oligodendroglial neoplasms: current concepts, misconceptions, and folklore.
AB  - Given current prognostic and therapeutic implications, the accurate
      classification and grading of oligodendroglial neoplasms has become critical.
      However, the prevalence of morphologically ambiguous gliomas, subjective
      histologic criteria, personal biases, oligodendroglioma mimics, and the lack of
      specific oligodendroglioma markers has led to high interobserver variability and
      created a contentious problem encountered daily in active surgical neuropathology
      practices. Since histologic assessment is still a powerful prognosticator, it
      appropriately remains the diagnostic gold standard. However, recent efforts have
      focused on identifying the most reproducible and clinically relevant criteria,
      standardizing classification and grading schemes, and searching for useful
      ancillary biologic and genetic markers capable of further stratifying an
      otherwise heterogeneous patient population. This paper reviews the morphologic
      and genetic spectrum of oligodendroglial neoplasms, recent diagnostic and
      prognostic developments, and potential future directions.

PMID- 11444509
TI  - Non-Hodgkin's lymphoma involving the gynecologic tract: a review of 88 cases.
AB  - Non-Hodgkin's lymphoma (NHL) involving the gynecologic tract is unusual and may
      cause confusion for the pathologist not familiar with its clinical and histologic
      features. The literature regarding this topic is also confusing, as modern NHL
      classification systems were not used or patients were not staged according to the
      Ann Arbor system in many prior reports. In addition, immunophenotypic data is not
      available for many cases, particularly in older studies. In the past year, there
      has been an interest in NHL involving the gynecologic tract and 88 cases have
      been collected. These cases were reviewed in the Pathology Department of M.D.
      Anderson Cancer Center during the past two decades, and many of these patients
      were treated at this hospital. In this review, these cases are reported using
      updated terminology and almost all cases were immunophenotyped using
      immunohistochemical methods or flow cytometric methods in a small subset of
      cases. These cases have also been segregated into two groups: 1) localized NHL,
      that presumably initially arose in the gynecologic tract and therefore are
      primary; and 2) NHL that involved the gynecologic tract as a part of systemic
      disease, and therefore most likely represent secondary involvement of the
      gynecologic tract. The differential diagnosis of NHL involving gynecologic organs
      is discussed.

PMID- 11444510
TI  - Lymphoma immunophenotyping: a new era in paraffin-section immunohistochemistry.
AB  - Recent advances in immunohistochemistry have made it possible to investigate
      lymphomas for the expression of a wide range of antigens in fixed tissues.
      Epitope retrieval, sensitive detection methods, and the availability of new
      monoclonal antibodies have all contributed to one's ability to perform detailed
      immunophenotyping that previously could only be done in cryostat sections or by
      flow cytometry. Current lymphoma classifications make use of characteristic
      immunophenotypic profiles that aid in the reproducible diagnosis and
      subcassification of these neoplasms. The following is a review of the current
      state of immunophenotyping for lymphoid neoplasms in fixed tissues.

PMID- 11444511
TI  - Early mycosis fungoides: can the diagnosis be made reliably?
AB  - The diagnosis of early mycosis fungoides is often regarded as difficult or
      impossible due to the lack of clear-cut histopathologic criteria. Many authors
      have published observations of histologic features seen in biopsies of patients
      with mycosis fungoides and have offered parameters that may be helpful in
      diagnosis. In the study, undertaken by members of the EORTC Cutaneous Lymphoma
      Study Group, the proposed histologic features are tested for sensitivity and
      specificity. This commentary discusses some of the historical issues and the
      value of the EORTC study pertaining to the diagnosis of early mycosis fungoides.

PMID- 11444512
TI  - MLC-based IMRT-Part II.

PMID- 11444513
TI  - Inverse planning for photon and proton beams.
AB  - The concept of inverse planning for intensity-modulated radiation therapy and its
      application for photon and charged particle beams is presented. Starting from
      theoretical solutions of the "inverse problem" in radiation therapy, a clinically
      applied optimization approach is discussed. A central topic is the mathematical
      formulation of clinical objectives in terms of physical parameters such as dose
      levels and irradiated volumes. Examples for practical inverse treatment planning
      and its clinical application for photon beams are provided. Inverse treatment
      planning of dose delivery techniques with charged particle beams is discussed by
      extending the conventional planning concept. A new multimodality inverse planning
      tool is described and applied to an example of comparative planning between
      photon and proton IMRT.

PMID- 11444514
TI  - Commissioning and quality assurance for MLC-based IMRT.
AB  - The commissioning and quality assurance (QA) associated with the implementation
      of linear accelerator multileaf collimator (MLC)-based intensity-modulated
      radiation therapy (IMRT) at the University of Nebraska Medical Center are
      described. Our MLC-based IMRT is implemented using the PRIMUS linear accelerator
      interface through the IMPAC record and verification system to the CORVUS
      treatment planning system. The "step-and-shoot" technique is used for this MLC
      based IMRT. Commissioning process requires the verification of predefined
      parameters available on the CORVUS and the collection of some machine data. The
      machine data required are output factor in air and output factor in phantom, and
      percent depth dose for a number of field sizes. In addition, inplane and
      crossplane dose profiles of 4 x 4 cm and 20 x 20 cm field sizes and diagonal dose
      profiles of a large field size have to be measured. Validation of connectivity
      and dose model includes the use of uniform intensity bar strips, triangular
      shaped nonuniform intensity bar strip, and N-shaped target. QA procedure follows
      the recommendation of the AAPM Task Group No. 40 report. In addition, the leaf
      position accuracy and reproducibility of the MLC should be checked at regular
      intervals. The dose validation is implemented through the hybrid plan where the
      patient beam parameters are applied to a flat phantom. Independent dose
      calculation method is used to confirm the dose delivery plan and data input to
      the CORVUS.

PMID- 11444515
TI  - Independent dose calculations for the corvus MLC IMRT.
AB  - Two independent dose calculation methods have been explored to validate MLC-based
      IMRT plans from the NOMOS CORVUS system. After the plan is generated on the
      CORVUS planning system, the beam parameters are imported into an independent
      workstation. The beam parameters consist of intensity maps at each gantry angle.
      In addition, CT scans of the patient are imported into the independent
      workstation to obtain the external contour of the patient. The coordinate system
      is defined relative to the alignment point chosen in the CORVUS plan. The 2
      independent calculation methods are based on a pencil beam kernel convolution and
      a Clarkson-type differential scatter summation, respectively. The pencil beam
      data for a 1 x 1-cm beam, as formed by the multileaf collimator, were measured
      for the 6-MV photon beam from a Siemens PRIMUS linear accelerator using film
      dosimetry. In the pencil beam method, the dose at a point is calculated using the
      depth and off-axis distance from a given pencil beam, corrected for beam
      intensity. The scatter summation method used the conversion of measured depth
      dose data into scatter maximum ratios. In this method, the differential scatter
      from each pencil beam is corrected for the beam intensity. Isodose distributions
      were generated using the independent dose calculations and compared to the CORVUS
      plans. Although isodose distributions from both methods show good agreement with
      the CORVUS plan, our implementation of the differential scatter summation
      approach seems more favorable. The 2 independent dose calculation algorithms are
      described in this paper.

PMID- 11444516
TI  - Intensity-modulated radiosurgery/radiotherapy using a micromultileaf collimator.
AB  - Intensity modulation with inverse treatment planning for 3 clinical stereotactic
      radiotherapy cases were directly compared against forward planning techniques
      using beam modification by enhanced dynamic wedge. Dose-volume histogram (DVH)
      analysis demonstrated that a significant reduction in dose to neighboring
      critical structures can-be achieved through intensity modulation patterns
      determined from inverse planning, while a marginal change is achieved in the
      target volume dose uniformity. This study also demonstrates that the intensity
      modulated dose patterns generated from inverse planning may differ significantly
      from the intuitive beam modified patterns developed in the forward planning
      model. These results suggest that one advantage of intensity modulated
      radiosurgery/radiotherapy with inverse planning is the significant reduction in
      dose to normal tissue and critical structures, with its coincident implications
      for dose escalation studies.

PMID- 11444517
TI  - Intensity modulation using multileaf collimators: current status.
AB  - Intensity-modulated radiation therapy (IMRT) extends the capability of 3D
      conformal methods (3D-CRT). Studies show that these methods can clinically reduce
      complications and can allow a larger safety margin for dose escalation. The
      ultimate goal is improved survival and improved quality of life. IMRT methods
      typically require more fields, or segments, and more monitor units for a given
      dose, as compared to conventional CRT methods. Because of this, some multileaf
      collimator (MLC) parameters take on more importance. A review of current standard
      MLC configurations are discussed, along with the concept of integral dose. An
      effective quality assurance (QA) program for IMRT involves more than dose
      modeling of the MLC. Integrity of data flowing from 3D radiograph databases to
      treatment planning to delivery sequencing files to verify-and-record function is
      required. End users need to be aware of differences in commercial availability
      vs. in-house developments for configuring a system. Great strides have been made
      in streamlining the whole process. This is evidenced by the first major symposium
      on community-based IMRT. Research continues to improve accuracy and productivity.

PMID- 11444518
TI  - Monte Carlo simulation for MLC-based intensity-modulated radiotherapy.
AB  - This article describes photon beam Monte Carlo simulation for multi leaf
      collimator (MLC)-based intensity-modulated radiotherapy (IMRT). We present the
      general aspects of the Monte Carlo method for the non-Monte Carloist with an
      emphasis given to patient-specific radiotherapy application. Patient-specific
      application of the Monte Carlo method can be used for IMRT dose verification,
      inverse planning, and forward planning in conventional conformal radiotherapy.
      Because it is difficult to measure IMRT dose distributions in heterogeneous
      phantoms that approximate a patient, Monte Carlo methods can be used to verify
      IMRT dose distributions that are calculated using conventional methods.
      Furthermore, using Monte Carlo as the dose calculation method for inverse
      planning results in better-optimized treatment plans. We describe both aspects
      and present our recent results to illustrate the discussion. Finally, we present
      current issues related to clinical implementation of Monte Carlo dose
      calculation. Monte Carlo is the most recent, and most accurate, method of
      radiotherapy dose calculation. It is currently in the process of being
      implemented by various treatment planning vendors and will be available for
      clinical use in the immediate future.

PMID- 11444519
TI  - Delivery systems of intensity-modulated radiotherapy using conventional multileaf
      collimators.
AB  - Intensity-modulated radiotherapy (IMRT) using conventional multileaf collimators
      (MLCs) has gained much attention in the radiation therapy community. To implement
      IMRT safely and efficiently, it is essential to understand the characteristics of
      MLCs, the associated delivery systems, and the limitations of each system when
      applied to IMRT. In this article, 3 major manufactured MLC collimators are
      reviewed, including the general descriptions such as the location of the MLC,
      whether or not it is single focused or double focused, the physical
      characteristics of leaves, the leaf movement restrictions, and the maximum
      achievable field size for IMRT delivery. MLC-based static and dynamic mechanisms
      are reviewed, and the delivery systems for these 3 collimators are described.
      Machine-related and patient plan-related quality assurance issues are discussed.
      Our conclusions are that MLC-based IMRT delivery is practical; however, extensive
      efforts are needed when IMRT is implemented in clinics.

PMID- 11444520
TI  - Dosimetric validation for multileaf collimator-based intensity-modulated
      radiotherapy: a review.
AB  - The creation of intricate dose distributions produced by intensity-modulated
      radiotherapy (IMRT) depends on complex planning systems and specialized
      mechanical devices. The many possible sources of inaccuracy and the complexity of
      the dose maps themselves require that a substantial effort be made to ensure that
      calculated and delivered dose distributions agree. This review provides an
      overview of the current status of the validation of dose predictions of IMRT
      planning systems by comparisons with measurements. Emphasis is placed on
      multileaf collimator- (MLC) based IMRT. Discrepancies between calculations and
      measurements may be due to any of 3 causes: errors and uncertainties in the dose
      calculation algorithm, in measurements, or in beam delivery by the
      accelerator/MLC combination. Some of the factors affecting dosimetry include: the
      technique employed for modulating the fluence, the dose calculation algorithm and
      other aspects of the planning system, mechanical limitations of the MLC hardware,
      dosimetric characteristics of the MLC, such as MLC leakage and rounded leaf ends,
      the choice of dosimeter, and the measurement geometry and technique. The
      advantages and drawbacks of various dosimeters including film, ion chambers,
      thermoluminescent dosimetry, and electronic portal imaging devices are discussed.
      The steps involved in validating dosimetrically a planning system are outlined,
      including the various fields that need to be measured, the phantoms that may be
      used, and measurement techniques. The achievable accuracy of dosimetry for IMRT
      is discussed.

PMID- 11444521
TI  - Inverse planning algorithms for external beam radiation therapy.
AB  - Intensity-modulated radiation therapy (IMRT) is a new treatment technique that
      has the potential to produce superior dose distributions to those of conventional
      techniques. An important step in IMRT is inverse planning, or optimization. This
      is a process by which the optimum intensity distribution is determined by
      minimizing (or maximizing) an objective function. For radiation therapy, the
      objective function is used to describe the clinical goals, which can be expressed
      in terms of dose and dose/volume requirements, or in terms of biological indices.
      There are 2 types of search algorithms, stochastic and deterministic. Typical
      algorithms that are currently in use are presented. For clinical implementations,
      other issues are also discussed, such as global minimum vs. local minima, dose
      uniformity in the target and sparing of normal tissues, smoothing of the
      intensity profile, and skin flash. To illustrate the advantages of IMRT, clinical
      examples for the treatment of the prostate, nasopharynx, and breast are
      presented. IMRT is an emerging technique that has shown encouraging results thus
      far. However, the technique is still in its infancy and more research and
      improvements are needed. For example, the effects of treatment uncertainties on
      the planning and delivery of IMRT requires further study. As with any new
      technology, IMRT should be used with great caution.

PMID- 11444522
TI  - Leaf sequencing techniques for MLC-based IMRT.
AB  - The nonuniform fields required by intensity-modulation radiation therapy (IMRT)
      can be delivered using conventional multileaf collimators (MLC) as beam
      modulators. In MLC-based IMRT, the nonuniform field is initially converted into
      an intensity map represented as a matrix of beam intensities. The intensity map
      is then decomposed into a series of subfields or segments of uniform intensities.
      Although there are many ways of segmenting the beam intensity matrix, a resulting
      subfield is only deliverable if it satisfies the constraints imposed by the MLC.
      These constraints exist as a result of the design of the MLC. The simplest
      constraint of the MLC is that its pairs of leaves can only move in and out in one
      dimension. Additional constraints include collision of opposing leaves and the
      need to match the tongue-and-groove to reduce interleaf leakage. The practical
      aspect of MLC-based IMRT requires that an optimized algorithm decomposes the
      nonuniform field into the least number of segments and therefore reduces the
      delivery time. This paper examines the static use and the dynamic use of MLCs to
      perform MLC-based IMRT.

PMID- 11444523
TI  - Dose verification for patients undergoing IMRT.
AB  - At Emory Clinic intensity-modulated radiation therapy (IMRT) was started by using
      dynamic multileaf collimators (dMLC) as electronic tissue compensators in August
      1998. Our IMRT program evolved with the inclusion of a commercially available
      inverse treatment planning system in September 1999. While the introduction of
      electronic tissue compensators into clinical use did not affect the customary
      radiation oncology practice, inverse treatment planning does alter our basic
      routines. Basic concepts of radiation therapy port designs for inverse treatment
      planning are different from conventional or 3D conformal treatments. With inverse
      treatment planning, clinicians are required to outline a gross tumor volume
      (GTV), a clinical target volume (CTV), critical normal structures, and to design
      a planning target volume (PTV). Clinicians do not designate the volume to be
      shielded. Because each IMRT radiation portal is composed of many beamlets with
      varying intensities, methods and practice used to verify delivered dose from IMRT
      portals are also different from conventional treatment portals. Often, the
      validity of measured data is in doubt. Therefore, checking treatment planning
      computer output with measurements are confusing and fruitless, at times.
      Commissioning an IMRT program and routine patient dose verification of IMRT
      require films and ionization chamber measurements in phantom. Additional
      specialized physics instrumentation is not required other than those available in
      a typical radiation oncology facility. At this time, we consider that routine
      quality assurance prior to patient treatments is necessary.

PMID- 11444524
TI  - IMRT: high-definition radiation therapy in a community hospital.
AB  - A multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT)
      program was implemented successfully at Monmouth Medical Center, a community
      hospital at Long Branch, New Jersey. Our clinical experience gained in the
      treatment of over 80 patients using IMRT for prostate, head and neck, and brain
      is reviewed, and some of the clinical issues are also, discussed. Implementation
      of the IMRT requires a treatment planning system, computer-controlled beam
      shaping aperture, electronic record and verify system, and a good physics quality
      assurance program. These components, by grouping them efficiently, have created a
      seamless workflow for our complete radiotherapy process of IMRT. Each of these
      radiotherapy processes are discussed for clarity and the clinical importance is
      also evaluated. Of particular interest is inverse treatment planning that will
      impact treatment delivery such as beam orientation, treatment ports, and organ
      motion of IMRT. A checklist for physics and departmental quality assurance is
      suggested, with the intention of providing systematic workflow, making IMRT
      feasible at a community medical center setting. This is especially important
      because most of our cancer patients received radiation therapy locally. Lastly,
      the reimbursement issue affecting the implementation of IMRT at our medical
      center is also discussed to justify this new treatment protocol for future
      clinical outcomes.

PMID- 11444525
TI  - Dosimetry bibliography.

PMID- 11444526
TI  - Responsiveness to transforming growth factor-beta (TGF-beta)-mediated growth
      inhibition is a function of membrane-bound TGF-beta type II receptor in human
      breast cancer cells.
AB  - Transforming growth factor-beta (TGF-beta) is a potent inhibitor of growth and
      proliferation of breast epithelial cells, and loss of sensitivity to its effects
      has been associated with malignant transformation and tumorigenesis. The
      biological effects of TGF-beta are mediated by the TGF-beta receptor complex, a
      multimer composed of TGF-beta receptor type I (TbetaR-I) and TGF-beta receptor
      type II (TbetaR-II) subunits. Evidence suggests that loss of expression of
      Tbeta3R-II is implicated in the loss of sensitivity of tumorigenic breast cell
      lines to TGF-beta-mediated growth inhibition. A panel of human breast cell lines,
      including the immortalized MCF-10F and tumorigenic MCF-7, ZR75-1, BT474, T47-D,
      MDA-MB231, BT20, and SKBR-3 cell lines, was characterized for responsiveness to
      TGF-beta-induced G1 growth arrest. Only the nontumorigenic MCF-10F and the
      tumorigenic MDA-MB231 cell lines demonstrated a significant inhibitory response
      to TGF-beta1 and a significant binding of 125I-labeled TGF-beta ligand. While
      expression of TbetaR-I mRNA was similar across the panel of cell lines, TbetaR-II
      mRNA expression was decreased significantly in all seven tumorigenic cell lines
      in comparison with the nontumorigenic MCF- 10F cell line. When total cellular
      protein was fractionated by centrifugation, TbetaR-I protein was observed in both
      the cytosolic and membrane fractions at similar levels in all cell lines;
      however, TbetaR-II protein was present in the cytosolic fraction in all cell
      lines, but was observed in the membrane fraction of only the TGF-beta-responsive
      MCF-10F and MDA-MB231 cells. Thus, lack of membrane-bound TbetaR-II protein
      appears to be an important determinant of resistance to TGF-beta-mediated growth
      inhibition in this group of breast cell lines.

PMID- 11444527
TI  - Peroxisome proliferator-activated receptor alpha-dependent induction of cell
      surface antigen Ly-6D gene in the mouse liver.
AB  - Spontaneous peroxisome proliferation-related pleiotropic responses occurring in
      the liver of mice lacking peroxisomal fatty acyl-CoA oxidase (AOX-/-) are
      attributed to sustained activation of peroxisome proliferator-activated receptor
      alpha (PPARalpha) by its putative natural ligands that require AOX for their
      metabolism. In this study, using a gene expression screen, we show that Ly-6
      (lymphocyte antigen 6 complex, locus D; mouse ThB), which belongs to a
      distinctive family of low molecular weight phosphatidyl inositol anchored cell
      surface glycoproteins, is upregulated in mouse liver with peroxisome
      proliferation. Increases in Ly-6D mRNA levels are observed in AOX-/- mouse liver
      with spontaneous peroxisome proliferation and also in the liver of wild-type mice
      treated with synthetic peroxisome proliferators. Peroxisome proliferators failed
      to increase hepatic Ly-6D mRNA levels in mice lacking PPARalpha (PPARalpha-/-),
      suggesting a regulatory role for PPARalpha in the induction of Ly-6D. These
      observations suggest that changes in certain cell surface proteins also form part
      of the pleiotropic responses associated with peroxisome proliferation.

PMID- 11444528
TI  - Inhibition of 5alpha-reductase in rat prostate reveals differential regulation of
      androgen-response gene expression by testosterone and dihydrotestosterone.
AB  - The growth and development of some of the male sex accessory organs such as the
      prostate requires the conversion of testosterone to dihydrotestosterone (DHT) by
      5alpha-reductase. To provide insights into the role of testosterone versus DHT in
      the prostate, we studied the impact of finasteride, a potent and specific
      inhibitor of 5alpha-reductase, on the expression of prostatic androgen-response
      genes in testis-intact rats and in 7-day castrated rats. Finasteride inhibition
      of the conversion of testosterone to DHT was confirmed by measuring serum and
      intraprostatic androgens. As expected, finasteride treatment caused a reduction
      in the wet weight of the prostate in the testis-intact rats and inhibited the
      testosterone-stimulated prostatic regrowth in the 7-day castrated rats. Although
      finasteride treatment had little or no effect on the expression of the surveyed
      androgen-response genes in testis-intact rats, its administration enhanced the
      expression of many androgen-response genes during the testosterone-stimulated
      regrowth of the regressed prostate in castrated rats. These observations suggest
      that testosterone is more potent than DHT in stimulating the expression of many
      androgen-response genes in the regressed prostate. The expression of androgen
      response genes is mainly prostate specific and thus is likely to be associated
      with androgen-dependent prostatic differentiation. Therefore, testosterone is
      more potent than DHT in inducing differentiation and weaker in stimulating
      proliferation during prostate regrowth. The fact that testosterone is a strong
      inducer of prostatic differentiation has potential clinical implications.

PMID- 11444529
TI  - Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro
      caspase-3 and cytochrome c.
AB  - Mitochondrial cytochrome c release in response to pro-apoptotic signals leads to
      the formation of a cytochrome c/Apaf-1/procaspase-9 complex (the apoptosome) and
      resultant activation of caspase-9 and caspase-3. Here we demonstrate that the
      molecular chaperone, Hsp27, inhibits this cytochrome c-mediated activation of
      caspase-3. Immunodepeletion of Hsp27 from cytochrome c-activated cytosols
      resulted in decreased caspase activity. Furthermore, immunoprecipitation of Hsp27
      resulted in the coprecipitation of both cytochrome c and procaspase-3. In
      reciprocal experiments, immunoprecipitation of both procaspase-3 and cytochrome c
      resulted in coprecipitation of Hsp27, indicating two independent interactions.
      These results point to Hsp27 mediating its inhibition of procaspase-3 activation
      through its ability to sequester both cytochrome c and procaspase-3, and thus
      prevent the correct formation/function of the apoptosome complex.

PMID- 11444530
TI  - Downregulation of constitutive and heavy metal-induced metallothionein-I
      expression by nuclear factor I.
AB  - Although the existence of repressor protein(s) involved in the regulation of
      highly inducible metallothionein-I (MT-I) gene expression has been postulated,
      none has been identified to date. We considered nuclear factor I (NFL) protein as
      a potential repressor, as three half-sites for NFI binding are present on MT-I
      promoter and NFI is known to downregulate several cellular gene promoters.
      Overexpression of all four isoforms of mouse NFI protein (NFI-A, -B, -C, and -X)
      suppressed both constitutive and heavy metal-induced activation of the MT-I
      promoter in HepG2 cells. However, unlike other target genes of NFI, direct
      interaction of NFI with MT-I promoter is not necessary to mediate its repression.
      Point mutation of the NFI binding sites within the MT-I promoter that abrogates
      NFI binding in vitro could not alleviate the repression. Similarly, NFI proteins
      also repress activity of minimal MT-I promoter deficient in the NFI binding
      sites. Further, an NFI-C deletion mutant lacking the DNA binding domain continued
      to repress MT-I promoter. Overexpression of MTF-1, the key trails-acting factor
      involved in MT-I gene transcription, surmounted NFI-mediated repression of the
      basal and zinc-induced MT-I promoter activity. These data demonstrate that NFI is
      a repressor of MT-I expression, where its DNA binding activity is not essential
      to downregulate the MT-I promoter. Interaction of NFI with another protein(s),
      probably MTF-I, may be involved in this repression.

PMID- 11444532
TI  - Blue-on-yellow perimetry with a scanning laser ophthalmoscope: small alterations
      in the central macula with aging.
AB  - The sensitivity of short-wavelength-sensitive (SWS) cone pathways was measured in
      the central fields of 74 normal subjects, aged 17-86 yr, with healthy maculas.
      The new fundus perimetry technique used a research scanning laser ophthalmoscope
      with a small entrance pupil to present blue static perimetry targets on a bright
      yellow background. Simultaneous infrared imaging aided target positioning and
      rapid assessment of potential pathology in elderly subjects. Targets were
      positioned peripheral to fixation, avoiding both the SWS-cone-free area and the
      peak macular pigment, determined in 11 subjects. Sensitivity declined 0.019 log
      unit per decade, while intraindividual variability across loci increased. The
      nasal-temporal asymmetry remained constant. Sensitivity of older subjects was
      relatively less for the most central targets but was unrelated to transmission
      through macular pigment. Retinal changes with age occur to differing extents or
      at differing rates and are readily detectable in the central macula.

PMID- 11444533
TI  - Effects of retinal scattering in the ocular double-pass process.
AB  - The validity of double-pass wave-front measurements in the eye is reviewed
      analytically and computationally. A mathematical description of the scalar
      optical field in the exit pupil plane after an ocular double-pass process is
      presented. With the help of this description, the relationship between the phase
      information losses and the statistical properties of retinal scattering is
      demonstrated.

PMID- 11444531
TI  - Atypical mouse cerebellar development is caused by ectopic expression of the
      forkhead box transcription factor HNF-3beta.
AB  - To assess the role of hepatocyte nuclear factor-3beta (HNF-3beta) in hepatocyte
      specific gene transcription, we reported the characterization of the liver
      phenotype with transgenic mice in which the -3-kb transthyretin (TTR) promoter
      functioned to increase HNF-3beta expression. During breeding of the TTR-HNF-3beta
      transgenic mice we noticed that they displayed severe ataxia. In this study, we
      describe the analysis of our transgenic cerebellar phenotype and demonstrate that
      ectopic expression of HNF-3beta disrupted cerebellar morphogenesis and caused
      reduction in cerebellar size. In postnatal cerebellum, the HNF-3beta transgene
      expression pattern is colocalized to glial fibrillary acidic protein-positive
      cerebellar astrocytes and Bergmann glial cells. As a result of protracted
      expression, the transgenic cerebella are impaired in terms of astrocyte dispersal
      and formation of Bergmann glial cell processes. This caused a disruption in
      neuronal cell migration to the cortical laminar layers and Purkinje dendritic
      arbor maturation, thus leading to diminished foliation. Differential
      hybridization of cDNA arrays was used to identify altered expression of
      cerebellar genes, which is consistent with the observed defect in transgenic
      cerebellar morphogenesis and size as well as glial maturation. These include
      diminished expression of the brain lipid-binding protein, which is required for
      glial morphological differentiation, and the basic helix-loop-helix NeuroD/Beta2
      and homeodomain Engrailed-2 transcription factors, which are required for normal
      cerebellar morphogenesis and foliation. Undetectable levels of ataxia
      telangiectasia (ATM), which is required for proper development of the Purkinje
      dendritic arbor, were found in postnatal transgenic cerebella. Furthermore, the
      transgenic cerebella displayed levels of insulin-like growth factor binding
      protein-1 elevated to 22 times greater than those measured for wild-type
      cerebella, an elevation consistent with the reduction in transgenic cerebellar
      size.

PMID- 11444534
TI  - Wavelength dependence of the Stiles-Crawford effect explained by perception of
      backscattered light from the choroid.
AB  - To explain the wavelength dependence of the directional sensitivity of human
      foveal cones (Stiles-Crawford I effect) we extended an existing fundus
      reflectance model for calculation of the total absorption by visual pigment. We
      took experimental data from literature for both the psychophysical and the
      optical Stiles-Crawford effect and optimized parameters to fit the experimental
      data. The wavelength dependence of the Stiles-Crawford effect could be well
      described with the geometrical optics model. Essential elements are self
      screening and the inclusion of backscattered choroidal light for perception.

PMID- 11444535
TI  - Calculation of optical imbalances in ophthalmic lenses using a new algorithm
      based on the local dioptric power matrix formalism.
AB  - We present a new algorithm to calculate the optical imbalances and differential
      prismatic effects that appear when two eyes look at an object through correcting
      eyeglasses. These are important magnitudes in ophthalmic optics because large
      amounts of them will disturb the binocular vision of the spectacle wearer. As a
      practical application of our algorithm, the distribution of optical imbalances
      and differential prismatic powers for a pair of progressive addition lenses has
      been calculated, and we obtain information about the effects of this kind of lens
      on the binocular vision of the wearer.

PMID- 11444536
TI  - Diffraction tomography reconstruction algorithms for quantitative imaging of
      phase objects.
AB  - A new reconstruction algorithm for phase-object imaging is proposed that is based
      on the principle of diffraction tomography and utilizes the Fourier
      transformation property of a finite-size phase object. From the measured
      scattered intensity, the imaginary part of the Fourier transform of the object
      can be extracted, and the three-dimensional structure of the object can be
      reconstructed. Numerical simulations show that the algorithm also can be used for
      a weak absorption object if the phase shift is much larger than the absorption.

PMID- 11444537
TI  - Rigorous electromagnetic analysis of a microcylindrical axilens with long focal
      depth and high transverse resolution.
AB  - We first present nonparaxial designs for a microcylindrical axilens with
      different long focal depths and rigorously analyze electromagnetic field
      distributions of the axilens using integral equations and the boundary-element
      method. Numerical results show that the designed axilenses indeed have the
      special feature of attaining a long focal depth while keeping high transverse
      resolution for numerical apertures of 2.4, 2.0, and 1.0. The ratio between the
      extended focal depth of the designed axilens and the focal depth of the
      conventional focal lens is 1.41, the corresponding maximal extended focal depth
      of the axilens can reach 28 microm, and the spot size of the focal beam is
      approximately 10 microm over the focal range.

PMID- 11444538
TI  - Spectral control of thermal emission by periodic microstructured surfaces in the
      near-infrared region.
AB  - Thermal emissive properties of microstructured surfaces are measured in the near
      infrared region. Two-dimensional periodic microstructured surfaces with metal
      coatings are fabricated with Si anisotropic etching and laser ablation
      techniques. The structural periods of the samples are 2.0 and 1.5 microm. Clear
      selective-emission bands are observed experimentally. This selective emission is
      attributed to the resonance effect between the emissive field and the surface
      microstructures. In addition, numerical calculation computed with rigorous
      coupled-wave analysis (RCWA) is performed on the microstructured samples. The
      selective-emission peaks measured through experiments can be reproduced well by
      RCWA, and this result suggests strongly that the thermal radiation from periodic
      structures may have spatial coherence. It is confirmed that the surface
      microstructure can be applied to the control of spectral emission from high
      temperature materials.

PMID- 11444539
TI  - Diffraction by a subwavelength-sized aperture in a metal plane.
AB  - We present an experimental study on the diffraction of light by an aperture small
      compared with the wavelength. The aperture is illuminated by laser light guided
      in a metal-clad tapered optical fiber. We investigate different orientations of
      the aperture in the plane: normal to the cleaved plane, oblique to the cleaved
      plane, and off-center. We measure the far-field, two-dimensional intensity
      distributions of the diffracted light as functions of angle coordinates theta and
      phi in a full half-space for various polarization states and analyze the patterns
      by using low-order multipole fields. We also examine the near- and far-field
      effects of placing small periodic corrugations near the aperture, focusing on the
      role of surface-wave excitations. We measure the near-field intensity
      distributions near the aperture with a near-field scanning optical microscope and
      discuss their relation to the far-field diffracted fields.

PMID- 11444540
TI  - Focusing diffractive cylindrical mirrors: rigorous evaluation of various design
      methods.
AB  - The performance characteristics of focusing diffractive mirrors designed with
      various methods are evaluated by using the rigorous boundary element method.
      Quantitative results are presented for (1) conventional-zero-thickness mirror
      designs, (2) alternative-zero-thickness designs that incorporate an off-axis
      correction factor and (3) finite-thickness designs. For TM polarization, the
      mirrors designed by using the alternative-zero-thickness method perform
      considerably worse than those designed by using the conventional-zero-thickness
      method, which contradicts predictions made in an earlier paper.

PMID- 11444541
TI  - Modeling considerations for rigorous boundary element method analysis of
      diffractive optical elements.
AB  - Critical modeling issues relating to rigorous boundary element method (BEM)
      analysis of diffractive optical elements (DOEs) are identified. Electric-field
      integral equation (EFIE) and combined-field integral equation (CFIE) formulations
      of the BEM are introduced and implemented. The nonphysical interior resonance
      phenomenon and thin-shape breakdown are illustrated in the context of a guided
      mode resonant subwavelength grating. It is shown that modeling such structures by
      using an open geometric configuration eliminates these problems that are
      associated with the EFIE BEM. Necessary precautions in defining the incident
      fields are also presented for the analysis of multiple-layer DOEs.

PMID- 11444542
TI  - High-order perturbation theory for light scattering from a rough metal surface.
AB  - The angular distribution of the mean diffuse intensity scattered from a metal
      surface with one-dimensional roughness is studied with perturbation theory. From
      an approach based on the reduced Rayleigh equations in p polarization, exact
      perturbation terms up to eighth order in the height parameter are developed for
      surface roughness consistent with a stationary Gaussian process. The theory is
      evaluated for a number of cases in which surface plasmon polariton excitation is
      significant and produces effects such as backscattering enhancement. For surface
      roughness having a wide Gaussian power spectrum, it is found that the high-order
      terms lead to roughness-induced broadening of the backscattering peak. For
      rectangular spectra, two cases are studied in which backscattering effects are
      due to sixth- and eighth-order terms; both cases provide good comparisons with
      previously unexplained experimental results. Further, because of an eighth-order
      term, the diffuse intensity is shown to contain a specular peak that also relies
      on polariton excitation. This new effect is studied in detail and is found to
      arise from the constructive interference of contributions produced by multiple
      scattering processes, although the time-reversed paths that produce
      backscattering enhancement are not essential to the specular effect.

PMID- 11444543
TI  - Variational solution for modal wave-front projection functions of minimum-error
      norm.
AB  - Common wave-front sensors such as the Hartmann or curvature sensor provide
      measurements of the local gradient or Laplacian of the wave front. The expression
      of wave fronts in terms of a set of orthogonal basis functions thus generally
      leads to a linear wave-front-estimation problem in which modal cross coupling
      occurs. Auxiliary vector functions may be derived that effectively restore the
      orthogonality of the problem and enable the modes of a wave front to be
      independently and directly projected from slope measurements. By using
      variational methods, we derive the necessary and sufficient condition for these
      auxiliary vector functions to have minimum-error norm. For the specific case of a
      slope-based sensor and a basis set comprising the Zernike circular polynomials,
      these functions are precisely the Gavrielides functions.

PMID- 11444544
TI  - Analytical solutions for time-resolved fluorescence lifetime imaging in a turbid
      medium such as tissue.
AB  - An analytical solution is developed to quantify a site-specific fluorophore
      lifetime perturbation that occurs, for example, when the local metabolic status
      is different from that of surrounding tissue. This solution may be used when
      fluorophores are distributed throughout a highly turbid media and the site of
      interest is embedded many mean scattering distances from the source and the
      detector. The perturbation in lifetime is differentiated from photon transit
      delays by random walk theory. This analytical solution requires a priori
      knowledge of the tissue-scattering and absorption properties at the excitation
      and emission wavelengths that may be obtained from concurrent time-resolved
      reflection measurements. Additionally, the solution has been compared with the
      exact, numerically solved solution. Thus the presented solution forms the basis
      for practical lifetime imaging in turbid media such as tissue.

PMID- 11444545
TI  - Optical cross-sectional imaging with pulse ultrasound wave assistance.
AB  - We have developed an optical cross-sectional imaging method for turbid media with
      the aid of a pulse ultrasound wave. Observation of deep regions in turbid media,
      such as tissue samples, is difficult owing to the rapid dispersion of an incoming
      laser beam by scattering. A pulse ultrasound wave, which is less scattered in
      tissues, can indicate the measuring point on the basis of the change of the
      optical scattering properties in a localized region. A depth-resolving capability
      can be achieved from the time-dependent measurement of the scattered-light
      intensity as the pulse ultrasound wave propagates in the sample. We verified the
      method by observing absorptive objects embedded in silicone rubber and by
      obtaining the cross-sectional image of an absorbing object surrounded by a strong
      scattering medium.

PMID- 11444546
TI  - Time-resolved Fourier optical diffuse tomography.
AB  - Time-resolved Fourier optical diffuse tomography is a novel approach for imaging
      of objects in a highly scattering turbid medium with use of an incident (near)
      plane wave. The theory of the propagation of spatial Fourier components of the
      scattered wave field is presented, along with a fast algorithm for three
      dimensional reconstruction in a parallel planar geometry. Examples of successful
      reconstructions of simulated hidden absorptive or scattering objects embedded
      inside a human-tissue-like semi-infinite turbid medium are provided.

PMID- 11444547
TI  - Optical dipole model for photodetection in the near field.
AB  - Near-field photodetection optical microscopy (NPOM) is a scanning probe technique
      that has been developed to perform nanometer-scale optical intensity mapping and
      spectroscopy. In NPOM a nanometer-scale photodiode detector absorbs power
      directly as it is scanned in the near field of an illuminated sample surface. A
      model of photodetection in the near and intermediate fields is presented. A brief
      review of far-field absorption is given for comparison. Far-field absorption
      measurements measure the imaginary part of the polarizability to first order. In
      contrast, photodetection in the near field measures the real part of the
      polarizability. Other aspects of near-field photodetection are also examined,
      including contrast mechanisms and lateral resolution. NPOM measurements performed
      on isolated 300-nm spheres show good agreement with the theory.

PMID- 11444548
TI  - Propagation and diffraction of locally excited surface plasmons.
AB  - With the use of optical near-field techniques, it is now possible to excite or
      observe surface plasmons with high lateral resolution. A theoretical study is
      presented of surface plasmon excitation by near-field optical probes and the
      influence of well-defined structures on surface plasmon propagation and surface
      plasmon detection in the far field. The generation and the diffraction of the
      surface plasmon is calculated by using a theoretical scheme founded upon a first
      order perturbation expansion of the Rayleigh-Fano method. A very good agreement
      is obtained between numerical and experimental results. The theoretical tools
      used should prove a useful guideline for future experiments of nanooptics with
      surface plasmons.

PMID- 11444549
TI  - Material parameter estimation with terahertz time-domain spectroscopy.
AB  - Imaging systems based on terahertz (THz) time-domain spectroscopy offer a range
      of unique modalities owing to the broad bandwidth, subpicosecond duration, and
      phase-sensitive detection of the THz pulses. Furthermore, the possibility exists
      for combining spectroscopic characterization or identification with imaging
      because the radiation is broadband in nature. To achieve this, we require novel
      methods for real-time analysis of THz waveforms. This paper describes a robust
      algorithm for extracting material parameters from measured THz waveforms. Our
      algorithm simultaneously obtains both the thickness and the complex refractive
      index of an unknown sample under certain conditions. In contrast, most
      spectroscopic transmission measurements require knowledge of the sample's
      thickness for an accurate determination of its optical parameters. Our approach
      relies on a model-based estimation, a gradient descent search, and the total
      variation measure. We explore the limits of this technique and compare the
      results with literature data for optical parameters of several different
      materials.

PMID- 11444550
TI  - High-aperture beams.
AB  - Beams of a high angle of convergence and divergence are called high-aperture
      beams. Different ways of defining high-aperture generalizations to paraxial beams
      are reviewed for both scalar beams and electromagnetic beams. The different
      approaches are divided into three types. The particular examples of Gaussian
      beams and Bessel beams are discussed. For Gaussian beams, beams that exhibit a
      Gaussian variation in the waist necessarily include evanescent components, which
      rules out their use in describing propagation over all space. Generalizations of
      the definitions of beam width and the beam-propagation factor M2 for high
      aperture beams are described. The similarities among the three types of high
      aperture beams and the different models of ultrashort-pulsed beams are discussed.

PMID- 11444551
TI  - Gaussian beam and pulsed-beam dynamics: complex-source and complex-spectrum
      formulations within and beyond paraxial asymptotics.
AB  - Paraxial Gaussian beams (GB's) are collimated wave objects that have found wide
      application in optical system analysis and design. A GB propagates in physical
      space according to well-established quasi-geometric-optical rules that can
      accommodate weakly inhomogeneous media as well as reflection from and
      transmission through curved interfaces and thin-lens configurations. We examine
      the GB concept from a broad perspective in the frequency domain (FD) and the
      short-pulse time domain (TD) and within as well as arbitrarily beyond the
      paraxial constraint. For the formal analysis, which is followed by physics
      matched high-frequency asymptotics, we use a (space-time)-(wavenumber-frequency)
      phase-space format to discuss the exact complex-source-point method and the
      associated asymptotic beam tracking by means of complex rays, the TD pulsed-beam
      (PB) ultrawideband wave-packet counterpart of the FD GB, GB's and PB's as basis
      functions for representing arbitrary fields, GB and PB diffraction, and FD-TD
      radiation from extended continuous aperture distributions in which the GB and the
      PB bases, installed through windowed transforms, yield numerically compact
      physics-matched a priori localization in the plane-wave-based nonwindowed
      spectral representations.

PMID- 11444552
TI  - Polarization basis for vortex beams.
AB  - Attention is called to a polarization basis formed by four Jones vectors that is
      reducible to two basic structures. In these states the field is linearly
      polarized at any point, but the polarization direction changes with the angular
      coordinate. Very simple equations hold for the field lines of these basis
      vectors. The adoption of this basis is of interest for beams possessing a single
      vortex of any order, say, m, as well as for beams with two vortices of opposite
      charges, m and -m. As an example, the application to vectorial Bessel-Gauss beams
      is briefly discussed.

PMID- 11444553
TI  - Nonparaxial Bessel-Gauss beams.
AB  - We study the nonparaxial propagation of Bessel-Gauss beams of any order. Closed
      form expressions of all corrections to be added to the solution that is pertinent
      to the corresponding paraxial problem are found. Such corrections are expressed
      in terms of two families of polynomials, defined through recurrence rules, that
      encompass the Laguerre-Gauss polynomials for the particular case of a fundamental
      Gaussian beam. Numerical examples are shown.

PMID- 11444554
TI  - Elegant Laguerre-Gauss beams as a new tool for describing axisymmetric flattened
      Gaussian beams.
AB  - A new superposition scheme for representing flattened Gaussian (FG) beams is
      proposed. Such a representation, unlike the original proposed by Gori [Opt.
      Commun. 107, 335 (1994)], is based on an expansion in terms of the so-called
      elegant Laguerre-Gaussian beams. This new representation allows us to obtain the
      closed-form expression of a FG beam of any order propagating through a paraxial
      ABCD optical system by means of a simple recurrence rule, which turns out to be
      particularly stable even when it is applied to FG beams of very high orders (>
      10(4)).

PMID- 11444555
TI  - Characterizing output beams for lasers that use high-magnification unstable
      resonators.
AB  - Laser beams generated from high-magnification on-axis unstable resonators by use
      of hard-edged optics typically have a doughnut-shaped distribution in the near
      field (i.e., a flat-top profile with a hole in the middle for an axially coupled
      beam). We derive analytical expressions describing this distribution by using the
      flattened Gaussian beams concept. The superposition of two flattened Gaussian
      beams whose flatness and steepness of edges are controlled by defined parameters
      (i.e., the beam width and the order) is used to analyze the output beam intensity
      along the propagation axis. Finally, experimental measurements of beam
      propagation from a copper-vapor laser fitted with a high-magnification unstable
      resonator show excellent agreement with theoretical predictions.

PMID- 11444556
TI  - Quasi-diffraction-free beams.
AB  - A diffraction-free beam is obtained by the superposing of plane waves whose wave
      vectors make an angle with the propagation axis. These plane waves are realized
      with point sources that are distributed uniformly around a circle and an
      infinitely large aperture lens. After the field passes through the lens it has
      nondiffracting properties and is described by the zero-order Bessel function.
      Relaxing these conditions makes the beam diffraction free within only a limited
      region. The beam generated from such a geometry is referred to as a quasi
      diffraction-free beam. The effects of the width of the annular source on the beam
      spread are discussed and compared with those for a Gaussian beam. Approximate
      expressions for quasi-diffraction-free beams are also obtained.

PMID- 11444557
TI  - Shape-invariance properties of a quartic-aberrated TEM00 Gaussian beam.
AB  - The concepts of shape-invariance error (SIE) and shape-invariance range (SIR)
      have recently been introduced to specify in a quantitative way the shape changes
      suffered by a beam on propagation. Here such parameters are evaluated for the
      case of a fundamental Gaussian beam in the presence of a quartic aberration of
      its wave front. Numerical results are presented for the case of a collimated
      aberrated beam. Generalization to the case of noncollimated beams is also given.

PMID- 11444558
TI  - Vectorial theory of propagation in uniaxially anisotropic media.
AB  - We describe propagation in a uniaxially anisotropic medium by relying on a
      suitable plane-wave angular-spectrum representation of the electromagnetic field.
      We obtain paraxial expressions for both ordinary and extraordinary components
      that satisfy two decoupled parabolic equations. As an application, we obtain, for
      a particular input beam (a quasi-Gaussian beam), analytical results that allow us
      to identify some relevant features of propagation in uniaxial crystals.

PMID- 11444559
TI  - Transmission of a two-dimensional Gaussian beam into a uniaxial crystal.
AB  - We study the transmission of a two-dimensional (2-D) TM Gaussian beam through a
      plane interface between an isotropic medium (e.g., air) and a uniaxially
      anisotropic crystal. The optic axis of the crystal is taken to be in the plane of
      incidence but is arbitrarily oriented relative to the interface normal. We show
      that, in the paraxial approximation, a nontruncated transmitted 2-D TM Gaussian
      beam inside a uniaxial crystal can be expressed in a form similar to that of a
      scalar Gaussian beam that propagates in a homogeneous medium. We also show that
      the transmitted beam corresponding to an incident 2-D TM Gaussian beam with its
      main propagation direction along the interface normal is tilted inside the
      crystal by the same angle as is the transmitted axial ray that corresponds to a
      normally incident ray.

PMID- 11444560
TI  - Transmission of a Gaussian beam into a biaxial crystal.
AB  - We derive integral representations that are suitable for studying the
      transmission of an electromagnetic Gaussian beam through a plane interface that
      lies between an isotropic medium and a biaxially anisotropic crystal for the case
      in which the interface normal is along one of the principal axes of the crystal.
      To that end, we use recently developed exact solutions for the transmitted fields
      to derive explicit expressions for the corresponding dyadic Green's functions as
      well as integral representations that are suitable for asymptotic analysis and
      efficient numerical evaluation.

PMID- 11444561
TI  - Vectorial structure of nonparaxial electromagnetic beams.
AB  - A representation of the general solution of the Maxwell equations is proposed in
      terms of the plane-wave spectrum of the electromagnetic field. In this
      representation the electric field solution is written as a sum of two terms that
      are orthogonal to each other at the far field: One is transverse to the
      propagation axis, and the magnetic field associated with the other is also
      transverse. The concept of the so-called closest field to a given beam is
      introduced and applied to the well-known linearly polarized Gaussian beam.

PMID- 11444562
TI  - Scattering of a Hermite-Gaussian beam field by a chiral sphere.
AB  - Scattering of a Hermite-Gaussian beam field by a chiral sphere is analyzed. A
      Hermite-Gaussian beam field is expressed as a superposition of multipole fields
      at complex-source points. Electromagnetic fields are expanded in terms of the
      spherical vector wave functions. The unknown expansion coefficients for the
      scattered field and the internal field are determined by the boundary conditions.
      As numerical examples, the scattered near fields of the beam incidence are
      calculated, and the effects of the chirality and the radius of the chiral sphere
      on the fields are examined. The results for a Gaussian beam incidence are also
      compared with those of a plane-wave incidence.

PMID- 11444563
TI  - Extinction and scattering of a guided beam in a hollow dielectric waveguide.
AB  - We present a theoretical approach to the problem of mode scattering by a
      spherical object that is placed inside a circular dielectric waveguide. This
      approach is based on the separation-of-variables method for each subsystem,
      namely, the spherical inclusion and the circular dielectric cylinder, and on the
      concept of the generalized recursive T-matrix algorithm for multilayered
      structures. We apply the technique to the backward and the forward scattering of
      a quasi-optical beam in the form of the fundamental HE11 mode by a sphere inside
      a circular hollow dielectric waveguide. The results calculated for the perfectly
      conducting spherical objects inside the circular hollow dielectric waveguide are
      compared with corresponding measured data of the backward-and the forward
      scattering characteristics at the 4-mm wave band.

PMID- 11444564
TI  - Radiation efficiency of partially coherent electromagnetic beams.
AB  - We present a general definition of the radiation efficiency of stationary
      electromagnetic fields and prove that it is bounded between zero and unity for
      beams of any state of coherence and polarization. The radiation efficiency may be
      interpreted as a measure of how directed the radiated fields are, and therefore
      it can be used to assess the allowed spatial coherence and intensity variations
      across a beam. We consider a class of partially coherent electromagnetic fields
      that were recently introduced in the literature and evaluate the radiation
      efficiencies for two particular examples, namely, the azimuthally polarized
      symmetric beams and the dipolar beams that are nearly linearly polarized in the
      central region. The results show that the radiation efficiency is fairly
      insensitive to the state of polarization and that it differs appreciably from
      unity for only small values of source and correlation widths.

PMID- 11444565
TI  - Asymptotic description of pulsed ultrawideband electromagnetic beam field
      propagation in dispersive, attenuative media.
AB  - The asymptotic description of the coupled spatial and temporal evolution of a
      pulsed ultrawideband electromagnetic beam field as it propagates through a
      dispersive, attenuative material that occupies the half-space z > or = z(0) is
      obtained from the angular spectrum of plane waves representation. This angular
      spectrum representation expresses the wave field as a superposition of both
      homogeneous and inhomogeneous plane waves. The paraxial approximation of the
      spatial part of this representation for nontruncated beam fields results in a
      description that explicitly displays the temporal evolution of the pulsed-beam
      field through a single-contour integral that is of the same form as that obtained
      for a pulsed plane-wave field propagating in the positive z direction in a lossy,
      dispersive medium. The accuracy of this paraxial approximation is shown to
      improve as the material's attenuation increases.

PMID- 11444566
TI  - Self-focusing and frequency broadening of an intense short-pulse laser in
      plasmas.
AB  - An intense ultrafast laser pulse propagating through a plasma undergoes self
      focusing and self-phase-modulation as a result of relativistic mass nonlinearity.
      The inclusion of a quartic (r4) term in the expansion of the eikonal in the
      radial coordinate r allows the modification of the shape of the radial intensity
      profile. The front of the pulse, under the combined effects of time-dependent
      self-focusing and frequency downshifting, acquires a severely distorted temporal
      shape. The radial profile for I(lambda)2(mu) < 2.8 x 1018 W/cm2, where I is the
      axial laser intensity and lambda(mu), is the laser wavelength in micrometers, is
      transformed from a Gaussian to a super-Gaussian because of the faster convergence
      of the marginal rays than the paraxial rays. In the opposite case of
      I(lambda)(2)(mu) > 2.8 x 10(18) W/cm2 when nonlinear plasma permittivity
      approaches saturation, the radial profile in the axial region becomes broader
      than the Gaussian.

PMID- 11444567
TI  - Role of the instantaneous spectrum on pulse propagation in causal linear
      dielectrics.
AB  - A model-independent theorem demonstrates how a causal linear dielectric medium
      responds to the instantaneous spectrum, that is, the spectrum of the electric
      field pulse that is truncated at each new instant (as a given locale in the
      medium experiences the pulse). This process leads the medium to exchange energy
      with the front of a pulse differently than with the back as the instantaneous
      spectrum laps onto or off of nearby resonances. So-called superluminal pulse
      propagation in either absorbing or amplifying media as well as highly subluminal
      pulse propagation are understood qualitatively and quantitatively within this
      context.

PMID- 11444568
TI  - Complete spatial characterization of a pulsed doughnut-type beam by use of
      spherical optics and a cylindrical lens.
AB  - A complete spatial characterization (in second-order moments) of a doughnut-type
      beam from a pulsed transversely excited atmospheric CO2 laser is described. It
      includes the measurement of the orbital angular momentum carried by the beam. The
      key element in the characterization is the use of a cylindrical lens in addition
      to the usual spherical optics. Internal features of the beam that would have
      remained hidden if only spherical optics were employed were revealed by use of
      the cylindrical lens. The experimental results are compared and agree with a
      theoretical Laguerre-Gauss mode beam.

PMID- 11444569
TI  - Time-resolved spatial profile of TEA CO2 laser pulses: influence of the gas
      mixture and intracavity apertures.
AB  - The evolution of the intensity profile of transversely excited atmospheric CO2
      laser pulses is investigated within the intensity moment formalism. The beam
      quality factor M2 is used to study the mode evolution. Attention is focused on
      the influence of both the gas mixture (N2 :CO2 :He) and the diameter of an
      intracavity diaphragm placed to attenuate higher-order modes. The degree of
      accuracy that can be attained by approximating the laser field amplitude by means
      of the lower-order terms of a Hermite-Gauss expansion is also analyzed. In
      particular, a bound for the truncation error is given in terms of two time
      resolved spatial parameters, namely the beam width and the M2 parameter.

PMID- 11444570
TI  - Photorefractive beam-fanning effect and self-pulsations in coated LiNbO3 slabs.
AB  - We investigate the dynamical behavior of optical Fabry-Perot resonators
      consisting of LiNbO3 slabs (x and c cut) that are coated with different
      (absorbing or lossless) dielectric multilayers deposited on both sides of the
      slabs. Bistable switching is observed experimentally. The buildup of beam fanning
      with time leads to destructive interference for a portion of the incident beam,
      inducing a change in absorption and heating, hence to switching off. As a result,
      self-pulsations appear whose frequency depends strongly on the input light
      intensity, the spot size, and the focusing. Switching and self-pulsations are not
      observed in the case of lossless coatings or for bare LiNbO3 slabs, although
      strong photorefractive beam fanning is still present. We also study the influence
      of the incident-beam characteristics (width and focusing) on the beam-fanning
      process and the pulsating behavior.

PMID- 11444571
TI  - Electromagnetic theory of an open resonator.
AB  - Particular higher-order sources give rise to electromagnetic Gaussian beams,
      which are linearly polarized and have their maximum in the propagation direction.
      For this dipolar beam the cross-sectional shape changes in the propagation
      direction. Nodal surfaces exist on which the tangential component of the electric
      field vanishes in the standing wave that is formed by the two oppositely directed
      dipolar, electromagnetic Gaussian beams. These surfaces are identified as the
      mirror shapes for an open resonator that supports this standing wave. For
      standing waves that have a particular cross-sectional shape at the waist the
      cross section of the beam near the mirror surfaces is circular. The resonant
      frequencies for the fundamental transverse mode of such a resonator have been
      determined as a function of the geometry and the axial mode number. By a
      perturbation technique the resonant frequency of an open resonator with spherical
      mirrors has been obtained. This result is valid in only the paraxial
      approximation. Illustrative numerical results are included.

PMID- 11444572
TI  - Corrugated waveguides as resonance optical filters--advantages and limitations.
AB  - The role of the excitation of guided waves propagating in a corrugated dielectric
      waveguide is discussed in view of the resonance anomalies in reflectivity. Narrow
      wavelength filtering properties that are due to these sharp anomalies have been a
      topic of interest for some time, but a proper understanding of device
      performances requires an analysis of tolerances with respect to the incident-beam
      collimation and to waveguide losses. Such an analysis is proposed in this paper,
      and the conclusion is that the incident-beam divergence plays a critical role in
      reducing the maximum reflectivity for narrow-band filters.

PMID- 11444573
TI  - Polarization conversion by reflection in a thin-film grating.
AB  - A dielectric-film waveguide with a grating etched on its film-cover interface can
      be used as a polarization converter. The e wave can be converted into the h wave
      and vice versa if the guided wave is incident obliquely to the grating vector.
      The polarization converter is analyzed by use of a quasi-optic technique. A high
      degree of polarization-conversion efficiency is achieved by a suitable choice of
      the grating length. The Bragg angles of incidence and observation, the maximum
      polarization-conversion efficiency, and the frequency and the angular selectivity
      are all found to increase with an increase in the grating period. An illustrative
      numerical example is presented.

PMID- 11444574
TI  - An evaluation of the hemostatic effects of hydrophilic, alcohol, and lipophilic
      extracts of notoginseng.
AB  - STUDY OBJECTIVE: To compare the hemostatic effects of hydrophilic, alcohol, or
      lipophilic extract of notoginseng with those of the control and placebo. DESIGN:
      Hemorrhagic rat model. SETTING: Hartford Hospital, Hartford, Connecticut; animals
      were housed at the Hartford Hospital animal facility. ANIMALS: Sixty-two male
      Wistar rats. Intervention. Administration of placebo (wheat flour), and alcohol,
      hydrophilic (water), and lipophilic (hexane) extracts of notoginseng. METHODS:
      Rats were divided into five groups, and their tails were transected 5 mm from the
      tip. Group 1 received no treatment (control), group 2 received placebo, group 3
      received alcohol extract, group 4 received hydrophilic extract, and group 5
      received lipophilic extract. Total bleeding time was determined and compared
      among the groups. MAIN RESULTS: Bleeding time was shorter for the placebo group
      than the control group (p=0.035). The alcohol extract group had the shortest
      bleeding time, which was significantly shorter than that of the control
      (p<0.0001), placebo (p=0.0124), and lipophilic extract groups (p=0.002). The
      hydrophilic extract group had a shorter bleeding time than the control group
      (p=0.0058) and showed a trend toward shorter bleeding time than the lipophilic
      extract group (p=0.068). CONCLUSIONS: The alcohol extract of notoginseng results
      in the shortest bleeding time and provides better hemostatic effects than no
      treatment, placebo treatment, and treatment with lipophilic extract.

PMID- 11444575
TI  - Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation.
AB  - P-glycoprotein (P-gp) is a cell membrane-associated protein that transports a
      variety of drug substrates. Although P-gp has been studied extensively as a
      mediator of multidrug resistance in cancer, only recently has the role of P-gp
      expressed in normal tissues as a determinant of drug pharmacokinetics and
      pharmacodynamics been examined. P-glycoprotein is present in organ systems that
      influence drug absorption (intestine), distribution to site of action (central
      nervous system and leukocytes), and elimination (liver and kidney), as well as
      several other tissues. Many marketed drugs inhibit P-gp function, and several
      compounds are under development as P-gp inhibitors. Similarly, numerous drugs can
      induce P-gp expression. While P-gp induction does not have a therapeutic role, P
      gp inhibition is an attractive therapeutic approach to reverse multidrug
      resistance. Clinicians should recognize that P-gp induction or inhibition may
      have a substantial effect on the pharmacokinetics and pharmacodynamics of
      concomitantly administered drugs that are substrates for this transporter.

PMID- 11444576
TI  - Role of coenzyme Q10 in chronic heart failure, angina, and hypertension.
AB  - PURPOSE: Coenzyme Q10 (CoQ10) has a pathophysiologic role in many disease states.
      The purpose of this review is to provide recommendations regarding the safety,
      efficacy, and dosing of CoQ10 in the management of chronic heart failure (CHF),
      angina, and hypertension. DATA SOURCES: Literature pertaining to the safety and
      efficacy of CoQ10 specifically in cardiovascular indications was reviewed. We
      used relevant clinical trials, articles, reviews, and letters that were selected
      from a literature search of the MEDLINE database (1974-2000), Micromedex
      Healthcare Series, and the Natural Medicines Comprehensive Database. FINDINGS:
      Coenzyme Q10 administered orally has favorable actions in the described
      cardiovascular conditions and appears to be safe and well tolerated in the adult
      population. Issues concerning optimum target dosages, potential interactions,
      monitoring parameters, and the role of CoQ10 as a monotherapeutic agent need to
      be investigated further. Favorable effects of CoQ10 on ejection fraction,
      exercise tolerance, cardiac output, and stroke volume are demonstrated in the
      literature; thus, the use of CoQ10 as adjuvant therapy in patients with CHF may
      be supported. CONCLUSIONS: Coenzyme Q10 therapy in angina and hypertension cannot
      be substantiated until additional clinical trials demonstrate consistent
      beneficial effects. However, CoQ10 may be recommended as adjuvant therapy in
      selected patients with CHE At this time, CoQ10 should not be recommended as
      monotherapy or first-line therapy in any disease state.

PMID- 11444577
TI  - Cholesterol risk management: a systematic examination of the gap from evidence to
      practice.
AB  - Hypercholesterolemia is a major risk factor for coronary heart disease, and data
      indicate that aggressive cholesterol reduction decreases mortality and morbidity
      associated with this disease. Many patients with hypercholesterolemia, however,
      are not screened, prescribed appropriate lipid-lowering therapy, or treated to
      target cholesterol levels. Practice patterns are particularly inadequate for
      those patients at highest risk for having a cardiac event. We performed a
      literature search to identify studies of practice patterns in the management of
      patients with hypercholesterolemia with regard to screening, implementing lipid
      lowering therapy, and treating to lipid goals. The findings highlight the
      potential for substantial opportunities to improve patient outcomes. Future
      studies should evaluate reasons for suboptimal cholesterol management as well as
      provide steps to improve management.

PMID- 11444578
TI  - Assessment of hypercholesterolemia control in a managed care organization.
AB  - To determine the extent of achievement of goal low-density lipoprotein
      cholesterol (LDL) as defined by National Cholesterol Education Program-Adult
      Treatment Panel II (NCEP-ATP 11) and American Diabetes Association (ADA) 2000
      guidelines, we conducted a retrospective study by integrating data from medical,
      laboratory, and pharmacy claims databases. Subjects were selected from a 232,000
      member staff-model managed care organization consisting of 19 clinics in the
      Minneapolis-St. Paul, Minnesota, metropolitan area. A total of 124,971 members
      aged 18 years and older, who had been continuously enrolled from July 1, 1996
      June 6, 1998, were included. Outcome measures were the extent of achievement of
      goal LDL as defined by NCEP-ATP II and the use of antihyperlipidemic drugs for
      patients with and without diabetes at various levels of risk for coronary heart
      disease (CHD). Of 124,971 subjects, 6538 had a history of CHD, 1523 of whom met
      their LDL goal. Of the population with CHD who did not achieve goal, 1141 (43%)
      missed by over 30 mg/dl; 621 (54%) of these patients were not receiving drug
      therapy A total of 17,267 had no history of CHD but had two or more risk factors;
      3,298 of these achieved their LDL goal. Of those who did not achieve goal, 1,136
      (35%) missed by over 30 mg/dl; 897 (79%) of these were not receiving drug therapy
      A total of 6,586 had a history of diabetes; 1,004 and 2,340 reached an LDL of 100
      mg/dl or lower and less than 130 mg/dl, respectively Of those with diabetes who
      had an LDL greater than 100 mg/dl, 1,276 (49%) missed their goal by over 30
      mg/dl; 898 (70%) of these were not receiving drug therapy. Inadequate use of
      pharmacologic agents plays a significant role in failure to achieve goal LDL for
      patients with CHD, without CHD, and with diabetes. Analysis of the data based on
      the new ADA guidelines for LDL demonstrates the need for continued vigilance.
      Finally, the successful merging of medical, laboratory, and pharmacy claims
      databases provides a benchmark for other institutions.

PMID- 11444579
TI  - Patient-reported adherence to guidelines of the Sixth Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
AB  - OBJECTIVES: To compare antihypertensive drug compliance with treatment guidelines
      established by the Sixth Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure (JNC VI), and to identify
      patient adherence to antihypertensive drugs and factors affecting prescribing
      patterns. METHODS: Patients filling antihypertensive drug prescriptions in
      metropolitan New York area pharmacies were enrolled. Pharmacy externs collected
      patient-reported demographics, medical and drug histories, and blood pressure
      measurements. Compliance with JNC VI guidelines was assessed. RESULTS: Eight
      hundred twenty-one patients from 102 pharmacies participated. Blood pressure was
      controlled in 61% of patients at the time of the study. The most prescribed class
      of antihypertensive agents was angiotensin-converting enzyme inhibitors, followed
      by diuretics and beta-blockers. Over the study period, compliance with JNC VI
      guidelines decreased significantly from 85% to 64% (p<0.05). Thirty-seven percent
      of patients reported consistent adherence to their antihypertensive regimens.
      Patients' education level was the only factor found to correlate positively with
      the appropriateness of antihypertensive agents prescribed. CONCLUSION: Compliance
      with JNC VI guidelines decreased over time, and patient adherence to drug therapy
      was suboptimal. Continuing-education efforts to reinforce optimal blood pressure
      management are necessary.

PMID- 11444580
TI  - Prepharmacy predictors of success in pharmacy school: grade point averages,
      pharmacy college admissions test, communication abilities, and critical thinking
      skills.
AB  - Good admissions decisions are essential for identifying successful students and
      good practitioners. Various parameters have been shown to have predictive power
      for academic success. Previous academic performance, the Pharmacy College
      Admissions Test (PCAT), and specific prepharmacy courses have been suggested as
      academic performance indicators. However, critical thinking abilities have not
      been evaluated. We evaluated the connection between academic success and each of
      the following predictive parameters: the California Critical Thinking Skills Test
      (CCTST) score, PCAT score, interview score, overall academic performance prior to
      admission at a pharmacy school, and performance in specific prepharmacy courses.
      We confirmed previous reports but demonstrated intriguing results in predicting
      practice-based skills. Critical thinking skills predict practice-based course
      success. Also, the CCTST and PCAT scores (Pearson correlation [pc] = 0.448, p <
      0.001) were closely related in our students. The strongest predictors of practice
      related courses and clerkship success were PCAT (pc=0.237, p<0.001) and CCTST (pc
      = 0.201, p < 0.001). These findings and other analyses suggest that PCAT may
      predict critical thinking skills in pharmacy practice courses and clerkships.
      Further study is needed to confirm this finding and determine which PCAT
      components predict critical thinking abilities.

PMID- 11444581
TI  - Retrospective analysis of serum valproate levels and need for an antidepressant
      drug.
AB  - We sought to determine whether patients receiving valproate plus an
      antidepressant had significantly lower serum valproate levels before initiation
      of the antidepressant than those patients receiving valproate without an
      antidepressant. We further sought to identify the prevalence of antidepressant
      induced mania and to determine if valproate provided a protective effect against
      antidepressant-induced mania. A computer database search from January 1, 1990
      June 30, 1998, identified patients with bipolar or schizoaffective disorder
      treated with valproate. Patients receiving an antidepressant during valproate
      therapy were identified as the treatment group (9 patients), and the remaining
      patients served as the control group (17 patients). Serum valproate levels were
      recorded just before starting the antidepressant for the treatment group and
      monthly during a comparable period for the control group. The mean time to
      antidepressant initiation was 15 +/- 8 weeks. The mean serum valproate level just
      before antidepressant initiation was significantly lower for the treatment group
      compared with the mean serum valproate level averaged over 16 +/- 6 weeks for the
      control group (54 +/- 24 vs 73 +/- 13 microg/ml, p<0.05). Four patients (44%)
      developed antidepressant-induced mania. Three required discontinuation of the
      antidepressant; their serum valproate levels were 54, 60, and 71 microg/ml.
      Patients requiring the addition of an antidepressant had significantly lower
      valproate serum levels than those who did not require an antidepressant. Further
      study is necessary to determine whether higher serum valproate levels are needed
      for prevention of depressive symptoms in bipolar and schizoaffective disorders.

PMID- 11444582
TI  - Cunninghamella bertholletiae infection in a bone marrow transplant patient:
      amphotericin lung penetration, MIC determinations, and review of the literature.
AB  - Infections caused by Cunninghamella bertholletiae, an opportunistic fungal
      organism, have an extremely high mortality rate. A fatal case of C. bertholletiae
      fungal pneumonia occurred in a man who had received an allogeneic bone marrow
      transplant. Aggressive debridement and high-dose liposomal amphotericin B failed
      to eradicate the infection. Right lung tissue samples obtained during lobectomy
      were assayed for amphotericin B concentrations by high-performance liquid
      chromatography, and minimum inhibitory concentration (MIC) determinations of
      amphotericin B against C. bertholletiae were determined by the macrobroth
      dilution method. The MIC for the isolate of C. bertholletiae was 4 microg/ml.
      Amphotericin B lung concentrations averaged 9.5 microg/ml (range 3.7-13.8
      microg/ml), with a corresponding serum trough concentration of 0.9 microg/ml. To
      our knowledge, this is the first reported case of amphotericin B concentrations
      measured at the site of infection in a patient with a pulmonary Cunninghamella
      infection, together with a corresponding MIC of the organism. The patient's
      death, which occurred despite aggressive debridement and high amphotericin B lung
      concentrations, highlights the need for novel strategies to treat infections
      caused by invasive molds such as C. bertholletiae.

PMID- 11444583
TI  - Lipodystrophy syndrome in children infected with human immunodeficiency virus.
AB  - Lipodystrophy syndrome (LDS), a fat-wasting condition commonly reported in adults
      infected with human immunodeficiency virus (HIV), has been linked to the use of
      antiretroviral agents. Recently, LDS was observed in children infected with HIV
      Little is known about the pathophysiology of this condition, although it is
      believed that LDS has many causes and modes of presentation. Even less is known
      about what long-term effects LDS will have on HIV-infected patients. Three
      patients who developed LDS were observed in a pediatric HIV clinic. Due to the
      lack of knowledge about the condition's natural course and the benefits versus
      risks of treatment, they were not treated specifically for LDS. Their lipid
      profiles, however, continue to be monitored closely twice/year.

PMID- 11444584
TI  - Possible roxithromycin-induced fulminant hepatic failure in a child.
AB  - A pediatric formulation of roxithromycin is a relatively new addition to the
      antibiotic market in Australia. A previously healthy 5-year-old boy with no
      significant medical history was treated with roxithromycin 50 mg twice/day for
      cough, fever, and anorexia. After completing a 5-day course of the agent, he
      developed a nonpruritic, nonurticarial, erythematous, maculopapular, generalized
      rash and occasional vomiting. Three days later his symptoms included jaundice,
      dark urine, and pale stools. Laboratory results revealed acute hepatitis, and the
      patient was admitted to the hospital. His hepatic function continued to
      deteriorate, so the boy was transferred to a tertiary pediatric hospital. His
      condition continued to worsen, and 6 days after transfer, he underwent liver
      transplantation. Clinicians should be aware of potential hepatic complications
      associated with the use of roxithromycin.

PMID- 11444585
TI  - Torsades de pointes associated with chlorpromazine: case report and review of
      associated ventricular arrhythmias.
AB  - PURPOSE: To present a case of chlorpromazine-associated torsades de pointes,
      review established cases of ventricular arrhythmias associated with
      chlorpromazine, and describe the proarrhythmic characteristics of this drug. DATA
      SOURCES: Articles identified through a search of MEDLINE and IDIS from January
      1966-November 2000 and thorough review of the article bibliographies. Patient
      cases also were identified from a search of the Food and Drug Administration's
      Adverse Event Reporting System database (November 1997-March 2001). Cases
      involving intentional overdoses of chlorpromazine were excluded. RESULTS: In
      addition to the case reported herein, 12 cases of documented, chlorpromazine
      associated ventricular arrhythmias were identified; five had characteristic
      features of torsades de pointes. Chlorpromazine delayed repolarization and
      produced electrocardiographic abnormalities; although, whether chlorpromazine
      induced torsades de pointes through a mechanism of early afterdepolarizations is
      unclear. Similar to other instances of drug-induced torsades de pointes,
      concurrent factors such as electrolyte deficiencies may place the patient at
      increased risk for arrhythmia. CONCLUSIONS: Chlorpromazine can delay
      repolarization and produce electrocardiographic abnormalities. These can result
      infrequently in ventricular arrhythmias and torsades de pointes, particularly in
      patients with confounding factors.

PMID- 11444586
TI  - Levofloxacin and warfarin interaction.
AB  - Numerous case reports have documented an enhanced hypoprothrombinemic effect
      caused by an interaction between fluoroquinolones (most notably, ciprofloxacin)
      and warfarin sodium. Conflicting data exist regarding the clinical significance
      of this interaction. Two patients who had elevated international normalized
      ratios after receiving concurrent levofloxacin and warfarin sodium are described.

PMID- 11444587
TI  - Fenofibrate and warfarin interaction.
AB  - A 79-year-old man with atrial fibrillation and coronary heart disease who was
      taking warfarin (Coumadin) was converted to fenofibrate from gemfibrozil therapy
      for persistently elevated triglyceride levels. The patient took fenofibrate for 1
      month and subsequently experienced rectal bleeding that required a visit to the
      emergency room. Before starting fenofibrate therapy, his coagulation values were
      within therapeutic range, but when measured in the emergency room the
      international normalized ratio (INR) was grossly elevated. The patient denied any
      changes in diet, alcohol ingestion, compliance with therapy, or use of other new
      drugs except for fenofibrate. His drug therapy profile consisted of digoxin,
      fosinopril, and furosemide for chronic heart failure, allopurinol for gout, and
      potassium supplementation. To minimize the risk of supratherapeutic INR values
      and/or hemorrhagic events, clinicians should perform serial monitoring of INR
      when initiating fenofibrate therapy in a patient previously stabilized on a
      coumarin anticoagulant.

PMID- 11444588
TI  - Increase of phosphoinositide hydrolysis and diacylglycerol production by PAF in
      isolated rat liver nuclei.
AB  - When isolated rat liver nuclei were treated with platelet-activating factor
      (PAF), a rapid increase in the mass of diacylglycerol (DAG) occurred. This effect
      was dose- and time-dependent. The maximum effect was observed after 1 min of 10(
      7) M PAF treatment. A concomitant decrease of polyphosphoinositides and
      phosphatidic acid (PA) levels was observed. PAF-induced DAG accumulation was
      inhibited by the treatment with WEB 2086 or PCA-4248, specific PAF-receptor
      antagonists. This result may suggest that PAF exerts its action in the nucleus
      through specific nuclear PAF binding sites. The findings described herein are due
      to the activation of phospholipase C, as the results from experiments using
      U73122, a phospholipase C inhibitor, indicate. These are the first data on the
      action of

PMID- 11444589
TI  - Molecular cloning and functional characterization of the canine prostaglandin E2
      receptor EP4 subtype.
AB  - Prostaglandin E2 (PGE2) is an important mediator of diverse biologic functions in
      many tissues and binds with high affinity to four cell surface, seven
      transmembrane domain, G protein-coupled receptors (EP1-EP4). The EP4 receptor
      subtype has a long intracellular carboxy-terminal region and is functionally
      coupled to adenylate cyclase, resulting in elevated intracellular cyclic
      adenosine 5' monophosphate (cAMP) levels upon activation. To further study EP4
      receptor subtype function, a canine kidney cDNA library was screened and three
      clones were isolated and sequenced. The longest clone was 3,103 bp and contained
      a single open reading frame of 1,476 bp, potentially encoding a protein of 492
      amino acids with a predicted molecular weight of 53.4 kDa. Sequence analysis of
      this open reading frame reveals 89% identity to the human EP4 protein coding
      region at the nucleotide level and 90% identity when the putative canine and
      human protein sequences are compared. Northern blot analysis showed relatively
      high levels of canine EP4 expression in heart, lung and kidney, while Southern
      blot analysis of canine genomic DNA suggests the presence of a single copy gene.
      Following transfection of canine EP4 into CHO-KI cells, Scatchard analysis
      revealed a dissociation constant of 24 nM for PGE, while competition binding
      studies using 3H-PGE2 as ligand demonstrated specific displacement by PGE2
      prostaglandin E, (PGE1), and prostaglandin A3 (PGA3). Treatment with PGE2 also
      resulted in increased levels of cAMP in transfected, but not in parental, CHO-KI
      cells. In contrast, butaprost, an EP2 selective ligand, and sulprostone, an
      EP1/EP3 selective ligand, did not bind to this receptor at the maximal
      concentration used (320 nM). To further investigate secondary signaling, the
      canine EP4 cDNA was truncated to produce an 1,117 bp fragment encoding a 356
      amino acid protein lacking the intracellular carboxy-terminus. When transfected,
      this truncated cDNA produced a protein with a dissociation constant of 11 nM for
      PGE2 and a binding and cAMP accumulation profile similar to that of the full
      length protein. Both full-length and truncated canine EP4 underwent short term
      PGE2-induced desensitization as shown by a lack of continuing cAMP accumulation
      after the initial PGE2 stimulation, suggesting no involvement of the C-terminal
      intracellular tail. This result is in contrast to that reported for the human EP4
      receptor, where residues within the C-terminal intracellular tail were shown to
      mediate short term, ligand induced desensitization.

PMID- 11444590
TI  - Aqueous flare elevation induced by transcorneal application of highly selective
      agonists for prostaglandin E2 receptor subtypes in pigmented rabbits: effect of
      tetramethylpyrazine.
AB  - We examined the disruptive effect of highly selective agonists for prostaglandin
      E2 receptor subtypes (EP1, EP2, EP3 and EP4) on the blood-aqueous barrier, and
      evaluated the inhibitory effect of tetramethylpyrazine, an active component of
      Ligusticum wallichii, on the elevation of aqueous flare induced by the EP
      agonists in pigmented rabbits. Highly selective EP agonists (ONO-DI-004, EP1
      agonist; ONO-AE1-259-01, EP2 agonist; ONO-AE-248, EP3 agonist; ONO-AE1-329, EP4
      agonist) at 12.5 to 250 microg/ml were transcorneally administered to the eyes of
      pigmented rabbits using a glass cylinder. Animals were pretreated intravenously
      with tetramethylpyrazine (10 or 30 mg/kg) 30 minutes before application of the
      EP2 or the EP4 agonist. Aqueous flare was measured using a laser flare-cell
      meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in
      arbitrary units. After administration of ONO-AE1-259-01 or ONO-AE1-329, aqueous
      flare increased and then gradually decreased. ONO-DI-004 and ONO-AE-248 had
      almost no effect on aqueous flare elevation. The AUC of eyes in rabbits
      pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was significantly
      smaller than that of eyes in rabbits treated with ONO-AEI-259-01 alone. The AUC
      of eyes in rabbits pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was
      not significantly smaller than that of eyes in rabbits treated with ONO-AEI-329
      only. The results indicated that EP2 and EP4 agonists induced aqueous flare
      elevation in pigmented rabbits, and that tetramethylpyrazine inhibited the
      aqueous flare elevation induced by the EP2 agonist but did not suppress the
      elevation induced by the EP4 agonist.

PMID- 11444591
TI  - Obesity is induced in mice heterozygous for cyclooxygenase-2.
AB  - In mice heterozygous for the cyclooxygenase-2 gene (COX-2+/-) the body weight was
      enhanced by 33% as compared to homozygous COX-2-/- mice. The weights of the
      gonadal fat pads in COX-2+/- mice were enhanced by 3.5 to 4.7 fold as compared to
      COX-2-/- mice and by 1.5 to 3.5 fold as compared to wild-type controls+/+ Serum
      leptin levels and leptin release by cultured adipose tissue of COX-2+/- mice were
      both elevated as compared to either control or COX-2-/- animals. The basal
      release of PGE2 or 6 keto PGF1alpha per fat pad over a 24 h incubation of adipose
      tissue was reduced by 80% and 95% respectively in tissue from COX-2-/- mice. NS
      398, a specific COX-2 inhibitor, inhibited leptin release by 27% in adipose
      tissue from control mice, 31% in tissue from COX-1-/- mice and by 23% in tissue
      from COX-2+/- mice while having no effect on leptin release by adipose tissue
      from COX-2-/- mice. These data indicate that heterozygous COX-2 mice develop
      obesity which is not secondary to a defect in leptin release by adipose tissue.

PMID- 11444592
TI  - The science and complexity of bitter taste.
AB  - Food choices and eating habits are largely influenced by how foods taste. Without
      being the dominant taste sensation, bitter taste contributes to the complexity
      and enjoyment of beverages and foods. Compounds that are perceived as bitter do
      not share a similar chemical structure. In addition to peptides and salts, bitter
      compounds in foods may include plant-derived phenols and polyphenols, flavonoids,
      catechins, and caffeine. Recent studies have shown that humans possess a
      multitude of bitter taste receptors and that the transduction of bitter taste may
      differ between one compound and another. Studies of mixture interactions suggest
      further that bitter compounds suppress or enhance sweet and sour tastes and
      interact with volatile flavor molecules. Caffeine, a natural ingredient of tea,
      coffee, and chocolate, has a unique flavor profile. Used as a flavoring agent, it
      enhances the sensory appeal of beverages. Research developments on the genetics
      and perception of bitter taste add to our understanding of the role of bitterness
      in relation to food preference.

PMID- 11444593
TI  - Nutrition transition in Latin America: the case of Chile.
AB  - The nutritional situation of Latin America is changing rapidly from one
      characterized by underweight and stunting to one where chronic diseases such as
      cancer, cardiovascular disease, and type 2 diabetes are increasingly prevalent.
      In Chile, under-nutrition has virtually disappeared, but rising obesity rates and
      risk factors for chronic diseases indicate the need to modify existing programs
      and emphasize prevention of diet-related chronic diseases.

PMID- 11444594
TI  - Insulin resistance associated with leptin deficiency in mice: a possible model
      for noninsulin-dependent diabetes mellitus.
AB  - Leptin deficiency, found in transgenic lipodystrophic mice and in obese (ob/ob)
      mice, was shown to cause increased lipogenesis in liver, through action of the
      sterol regulatory element-binding protein-1c, and increased liver
      gluconeogenesis, through a decline in the insulin receptor substrate-2. The
      resulting stimulation of insulin secretion by the pancreas owing to high blood
      glucose initiates a vicious cycle of insulin resistance.

PMID- 11444595
TI  - Are eating disorders more prevalent in females with type 1 diabetes mellitus when
      the impact of insulin omission is considered?
AB  - Although prevalence estimates vary in women with type 1 diabetes mellitus,
      studies suggest the occurrence of eating disorders is comparable between women
      with and without diabetes mellitus. A new study examined the association between
      eating disorders and type 1 diabetes mellitus in 12-19-year-old females with
      diabetes for at least 1 year. Subjects with diabetes were 2.4 times more likely
      than controls (without diabetes) to have a clinical eating disorder and 1.9 times
      more likely to have a subthreshold eating disorder. Moreover, mean glycosylated
      hemoglobin was higher in subjects with diabetes who had an eating disorder (9.4%)
      compared with those with diabetes without an eating disorder (8.6%).

PMID- 11444596
TI  - Listeria monocytogenes: a continuing challenge.
AB  - As a leading cause of death from a foodborne pathogen, Listeria monocytogenes
      continues to cause sporadic cases and outbreaks of illness. The most recent of
      these outbreaks in the United States involved consumption of hot dogs, with 101
      cases of illness and 21 deaths reported to the Centers for Disease Control and
      Prevention for the years 1998-1999. Epidemiologic analysis determined that
      contamination levels in hot dogs were remarkably low (0.3 CFU [colony-forming
      units] L monocytogenes serotype 4b/g). That same year, manufacturers of hot dogs
      and luncheon meats collectively recalled more than 500,000 pounds of product
      owing to possible Listeria contamination. This article, through focus on issues
      such as reexamination of zero-tolerance policies, improvements in detection and
      enumeration procedures, the impact of epidemiologic innovations, and measures
      needed to further reduce the incidence of listeriosis will highlight why L
      monocytogenes remains a continuing challenge for the food industry.

PMID- 11444597
TI  - Electrospray ionization and tandem mass spectrometry of cysteinyl eicosanoids:
      leukotriene C4 and FOG7.
AB  - The cysteinyl leukotrienes, LTC4, LTD4 and LTE4, and the recently described
      cysteinyl eicosanoid, 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid (FOG7)
      have been analyzed by tandem mass spectrometry. Both [M-H]- and [M+H]+ ions were
      produced by electrospray ionization and collision-induced dissociation of these
      molecular ion species were studied using both an ion trap and a triple quadrupole
      instrument. Product ion spectra obtained were characteristic of the structure of
      the cysteinyl leukotrienes and mechanisms of ion formation were investigated by
      using deuterium-labeled analogs. The product ion spectrum obtained following
      collision-induced dissociation of the [M-H]- anion from FOG7 was devoid of
      significant structural information and further studies of collision activation of
      the [M+H]+ spectrum were therefore examined. Positive ion MS3 spectra obtained in
      the ion trap from the gamma-glutamate cleavage products of FOG7 and its
      derivative (d7-FOG7) afforded an abundant ion not observed in spectra generated
      from the cysteinyl leukotrienes. Formation of this fragment ion likely occurred
      via a McLafferty-type rearrangement to afford cleavage of the C6-C7 bond adjacent
      to the sulfur atom and was valuable for the identification of the structure of
      FOG7 and defining the biosynthetic pathway as a 1,4-Michael addition of
      glutathione to 5-oxo-eicosatetraenoic acid (5-oxo-ETE).

PMID- 11444598
TI  - Collision-induced dissociation of bradykinin ions in the interface region of an
      ESI-MS.
AB  - By applying different electric field strengths to the orifice-skimmer region of
      an electrospray ionization mass spectrometer, the rate of dissociation can be
      varied based on the amount of internal energy acquired by an ion through
      collisions with the curtain gas molecules. Both the Arrhenius equation and Rice
      Ramsperger-Kassel (RRK) theory can be used to predict the rate of dissociation of
      internally excited molecules. A previously determined model for collision-induced
      dissociation is tested by comparison of predicted and experimentally observed
      orifice-skimmer potential differences for dissociation of ions. The rate of
      collision-induced dissociation of bradykinin ions is determined by monitoring the
      fragments produced in a mass spectrometer. The semi-quantitative model is found
      to yield effective predictions when accurate Arrhenius and RRK parameters are
      utilized.

PMID- 11444599
TI  - Gas phase RNA and DNA ions 2. Conformational dependence of the gas-phase H/D
      exchange of nucleotide-5'-monophosphates.
AB  - The conformational dependence of the gas-phase hydrogen/deuterium (H/D) exchange
      of nucleotide-5-monophosphate anions with the H/D exchange reagent D2S is
      reported here. The electrospray-generated [M-H]- anions of adenosine-5'
      monophosphate, adenosine-5'-carboxylic acid, ribitol-5-phosphate, and 2-deoxy
      ribitol-5-phosphate were reacted with D2S in the gas phase. Their reactivity
      (adenosine-5'-monophosphate exchanged 2 of 5 labile hydrogens, adenosine-5'
      carboxylic acid exchanged 1 of 4, ribitol-5-phosphate exchanged 2 of 3, and 2
      deoxy-ribitol-5-phosphate exchanged 1 of 2) suggests that the hydroxyl group in
      the 2 position of the ribose sugar and the amino hydrogen on the nucleobase do
      not exchange readily with D2S. Semiempirical molecular orbital calculations
      suggest that the labile hydrogens in these positions are thermodynamically facile
      to exchange but as a conformation inaccessible to the presumed phosphate anion,
      consistent with a mechanism in which the phosphate anion complexes with the
      exchange reagent and assists H/D exchange at a neighboring site.

PMID- 11444600
TI  - A study of kynurenine fragmentation using electrospray tandem mass spectrometry.
AB  - A combination of accurate mass measurement and tandem mass spectrometry (both
      product ion and precursor ion scans) have been used to characterize the major
      fragment ions observed in the ESI mass spectrum of kynurenine. Kynurenine is a
      metabolite of tryptophan found in the human lens and is thought to play a role in
      protecting the retina from UV-induced damage. Three major fragmentation pathways
      were evident, following initial elimination either of ammonia, H2O and CO or the
      imine form of glycine. The latter is proposed to occur via the formation of an
      ion-molecule complex. In the case of loss of H2O and CO from deaminated
      kynurenine, there is evidence for an acylium ion intermediate, which is not
      observed for the loss of H2O and CO directly from protonated kynurenine. Product
      ion scans of deuterated kynurenine enabled the elucidation of structural
      rearrangements that were not evident in the spectra of the native compound. Since
      UV filter compounds can often only be isolated in small quantities from the lens,
      this study forms the basis for the characterization of novel UV filter compounds
      using mass spectrometry. The approach presented here may also be useful for the
      characterization of related classes of small molecules.

PMID- 11444601
TI  - Using solution phase hydrogen/deuterium (H/D) exchange to determine the origin of
      non-covalent complexes observed by electrospray ionization mass spectrometry: in
      solution or in vacuo?
AB  - Electrospray ionization (ESI) is a soft ionization technique that is able to
      transfer intact ions, as well as solution phase non-covalent complexes into the
      gas phase. With small molecules that have a high tendency to form hydrogen bonds,
      the observation of non-covalent complexes by ESI-MS can be the result of a non
      specific interaction, due to the nature of the electrospray process. Special
      precautions and additional steps should be performed to identify the origin of
      the complexes observed with ESI-MS, and we have utilized solution phase
      hydrogen/deuterium (H/D) exchange as a method to determine the specificity of the
      complexes. By comparing the average number of exchanges for the monomer subunits
      to the average number of exchanges for the complex, one can distinguish if a
      specific complex is formed in solution. In this paper we have investigated non
      covalent complexes of some common chemotherapy agents: paclitaxel, doxorubicin,
      and etoposide by ESI-MS. By using the solution phase H/D exchange, we were able
      to identify several specific drug-drug complexes. Thus, solution phase H/D
      exchange combined with ESI-MS provides for a convenient method in ascertaining
      the specificity of non-covalent complexes as being formed in solution or in
      vacuo.

PMID- 11444602
TI  - Complete sequencing of mono-deprotonated peptide nucleic acids by sustained off
      resonance irradiation collision-induced dissociation.
AB  - Complete peptide nucleic acids (PNAs) sequence information is obtained from the
      unimolecular decomposition of singly-charged PNA oligomers in the negative-ion
      mode using electrospray ionization coupled with Fourier transform ion cyclotron
      resonance mass spectrometry (ESI-FTICR-MS) and sustained off-resonance
      irradiation collision induced dissociation. The 4-mers, n-CATT-c, n-AGCT-c, n
      AACT-c, and n-acetylated-AACT-c and two 6-mers, n-AAAAAA-c and n-CCCCCC-c, were
      investigated to explore the unimolecular decomposition of mixed-nucleobase and
      homopolymer PNAs representing purine and pyrimidine oligomers, respectively. PNA
      decomposition is explored using a product-ion appearance curve and double
      resonance experiments. A decomposition mechanism for sequence ion formation (PNA
      amide bond cleavage) is proposed.

PMID- 11444603
TI  - Protein structure information from mass spectrometry? Selective titration of
      arginine residues by sulfonates.
AB  - Noncovalently bound complexes between basic sites of peptides/proteins and
      sulfonates are studied using Matrix Assisted Laser Desorption/Ionization (MALDI)
      Mass Spectrometry. Reactive sulfonate dyes such as Cibacron Blue F3G-A are known
      to bind to protonated amino groups on the exterior of a protein. In this work, we
      examine a wide range of other sulfonates with distinctly simpler structure and
      more predictable reactivity. Naphthalene-sulfonic acid derivatives were found to
      bind to arginine only, as opposed to expected binding to all basic sites (Arg,
      Lys and His). Detailed control experiments were designed to unambigously confirm
      this selectivity and to rule out nonspecific adduct formation in the gas phase.
      The data show that the number of complex adducts found equals the number of
      accessible arginine sites on the surface of folded peptides and proteins, plus
      the N-terminus. Lys and His are not complexed nor are buried residues with
      hindered access. MALDI-MS can therefore provide fast information related to the
      exposed surface of these biomolecules. Additional titration experiments with 1
      anilino-naphthalene-8-sulfonic acid (ANS) revealed that this fluorescent dye,
      which was often hypothesized to bind to so-called molten globule states of
      proteins, behaved exactly like all other naphthalene-sulfonic acids. ANS binding
      thus occurs largely through the sulfonate group.

PMID- 11444604
TI  - First observation by mass spectrometry of a 3+ oxidation state for a [4Fe-4S]
      metalloprotein: an ESI-FTICR mass spectrometry study of the high potential iron
      sulfur protein from Chromatium vinosum.
AB  - Electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass
      spectrometry (FTICR) is used to measure the molecular weight of the high
      potential iron-sulfur protein (HiPIP) from Chromatium vinosum (C. vinosum) and
      its corresponding apoprotein. By accurate mass measurement of the metalloprotein,
      the oxidation state of the [4Fe-4S] metal center is assigned as 3+. This is the
      highest oxidation state yet observed by mass spectrometry for a [4Fe-4S] cluster,
      which usually appears in the 2+ oxidation state. In order to make this assignment
      correctly, the mass spectrum of the apoprotein was acquired, and a 1 Da
      difference was found between the molecular mass of the apoprotein and its
      published amino acid sequence. The mass spectra of the trypsin and cyanogen
      bromide digests of the alkylated apoprotein were obtained, and the data suggests
      that the C-terminal glycine residue is amidated.

PMID- 11444605
TI  - Application of ion-impact energy measurement to electrospray ionization mass
      spectrometry of proteins and protein mixtures.
AB  - We have used a normal metal-insulator-superconductor (NIS) microcalorimeter to
      measure the impact energy of protein ions produced by electrospray ionization
      (ESI) in a magnetic-sector mass spectrometer (MS). We have used these
      measurements to resolve spectral ambiguities and to analyze protein mixtures.
      Energy measurement may be useful for the direct MS analysis of complex biopolymer
      mixtures that normally would confound ESI-MS deconvolution algorithms.

PMID- 11444606
TI  - Lithium and transition metal ions enable low energy collision-induced
      dissociation of polyglycols in electrospray ionization mass spectrometry.
AB  - Electrospray ionization tandem mass spectrometry has the potential to be widely
      used as a tool for polymer structural characterization. However, the backbones or
      molecular chains of many industrial polymers including functional polyglycols are
      often difficult to dissociate in tandem mass spectrometers using low energy
      collision-induced dissociation (CID). We present a method that uses Li+ and
      transition metal ions such as Ag+ as the cationization reagents for electrospray
      ionization in an ion trap mass spectrometer. It is shown that lithium and
      transition metal polyglycol adduct ions can be readily fragmented with low energy
      CID. Comparative results from different cationization reagents in their abilities
      of producing both MS spectra and CID spectra are shown. This method opens the
      possibility of using conventional and readily available low energy CID tandem MS
      to study polyglycol structures.

PMID- 11444607
TI  - The structure of ionized 1,5 hexadiene in the gas phase.
AB  - The structure of ionized 1,5-hexadiene, prepared by charge transfer between 1,5
      hexadiene and CS2+*, is examined using energy-resolved collision-induced
      dissociation (CID). By comparing the product distributions and product appearance
      curves with those of authentic low-energy C6H10+* ions, it is determined that 1,5
      hexadiene cation spontaneously rearranges to cyclohexene cation in the gas-phase.
      The proposed mechanism for formation of cyclohexene cation in the gas phase is
      analogous to that determined for this process under matrix isolation conditions,
      where it proceeds via a Cope rearrangement to the cyclohexane-1,4-diyl cation,
      followed by isomerization to cyclohexene cation. It is shown that electron
      ionization (EI) of 1,5-hexadiene gives a different molecular ion than is obtained
      upon chemical ionization (CI). The energy-resolved CID mass spectrum for the EI
      product is consistent with what would be obtained for a mixture of low energy ion
      isomers.

PMID- 11444608
TI  - Biopolymer sequencing using a triple quadrupole mass spectrometer in the ESI
      nozzle-skimmer/precursor ion MS/MS mode.
AB  - A variety of model biopolymers, including oligonucleotides, oligosaccharides and
      a synthetic pharmaceutical agent, were sequenced using a triple quadrupole mass
      spectrometer equipped with an electrospray source and operated in a scan mode
      referred to as pseudo-MS3. This scan mode consists of three steps: (1) in-source
      collision-induced dissociation (CID) in the nozzle-skimmer (NS) region, (2)
      scanning of the fragment ions into the collision cell for further CID, and (3)
      passing of the secondary fragment ions through the final mass filter at a
      preselected mass, generally corresponding to the mass of a terminal sequence ion
      for the biopolymer. The mass spectra are recorded in the precursor ion MS/MS mode
      where ion selection and detection occur at the third stage of the triple
      quadrupole but the scan function is determined by the first stage. The advantages
      and limitations in using this pseudo-MS3 NS/precursor ion MS/MS scan mode for
      biopolymer sequencing are discussed.

PMID- 11444609
TI  - Electrochemical processes in a wire-in-a-capillary bulk-loaded, nano-electrospray
      emitter.
AB  - Experiments are described that illustrate solvent oxidation, emitter electrode
      corrosion, and analyte oxidation in positive ion mode nano-electrospray mass
      spectrometry using a wire-in-a-capillary, bulk-loaded nano-electrospray emitter
      geometry. Time-lapsed color photography of pH and metal specific indicator
      solutions within operating nano-electrospray emitters, as well as temporal
      changes in the ions observed in the nano-electrospray mass spectra, are used to
      probe these reactions, judge their magnitude, and study the time dependent
      changes in solution composition and gas-phase ion signal brought about as a
      result of these electrochemical reactions. The significance of these observations
      for analytical applications of nano-electrospray mass spectrometry are discussed.

PMID- 11444610
TI  - Quantitative selected ion flow tube mass spectrometry: the influence of ionic
      diffusion and mass discrimination.
AB  - Selected ion flow tube mass spectrometry, (SIFT-MS), involves the partial
      conversion of mass-selected precursor ions to product ions in their reactions
      with the trace gases in an air sample that is introduced into helium carrier gas
      in a flow tube. The precursor and product ions are then detected and counted by a
      downstream quadrupole mass spectrometer. Quantification of particular trace gases
      is thus achieved from the ratio of the total count rate of the product ions to
      that for the precursor ions. However, it is important to appreciate that in this
      ion chemistry the light precursor ions (usually H3O+ ions) are invariably
      converted to heavier product ions. Hence, the product ions diffuse to the flow
      tube walls more slowly and thus they are more efficiently transported to the
      downstream mass spectrometer sampling orifice. This phenomenon we refer to as
      diffusion enhancement. Further, it is a well-known fact that discrimination can
      occur against ions of large mass-to-charge ratio, (m/z), in quadrupole mass
      spectrometers. If not accounted for, diffusion enhancement usually results in
      erroneously high trace gas concentrations and mass discrimination results in
      erroneously low concentrations. In this experimental investigation, we show how
      both these counteracting effects can be accounted for to increase the accuracy of
      SIFT-MS quantification. This is achieved by relating the currents of ions of
      various m/z that arrive at the downstream mass spectrometer sampling orifice disc
      to their count rates at the ion detector after mass analysis. Thus, both
      diffusion enhancement and mass discrimination are parameterized as a function of
      m/z and these are combined to provide an overall discrimination factor for the
      particular analytical instrument.

PMID- 11444611
TI  - Dissociation reactions of gaseous ferro-, ferri-, and apo-cytochrome c ions.
AB  - Electrochemical reduction of the iron bound in the heme group of cytochrome c is
      shown to occur in the nano-electrospray capillary if the protein is sprayed from
      neutral water using a steel wire as the electrical contact. Quadrupole ion trap
      collisional activation is used to study the dissociation reactions of cytochrome
      c as a function of the oxidation state of the iron. Oxidized (Fe(III)) cytochrome
      c dissociates via sequence-specific amide bond cleavage, while the reduced
      (Fe(II)) form of the protein dissociates almost exclusively by loss of protonated
      heme. Apo-cytochrome c, from which the heme has been removed either via gas-phase
      dissociation of the reduced holo-protein or via solution chemistry, dissociates
      via amide bond cleavage in similar fashion to the oxidized holo-protein.

PMID- 11444612
TI  - Sudan: the possible original focus of visceral leishmaniasis.
AB  - Fifty-two Leishmania strains, obtained from human patients and dogs in a visceral
      leishmaniasis focus in Sudan, were characterized by isoenzyme electrophoresis (15
      enzymes). The phylogenetic analysis showed that the 7 Leishmania zymodemes
      obtained hold ancestral positions on the phylogenetic tree, supporting the
      hypothesis of an East African origin of visceral leishmaniasis.

PMID- 11444613
TI  - Diagnosis of infections with Leishmania infantum using PCR-ELISA.
AB  - On the basis of partial amplification of a cloned fragment of kDNA of Leishmania
      infantum which is specific for this species, we developed a PCR-ELISA technique
      which avoids the problems associated with classical diagnostic techniques. This
      technique was tested on 33 L. infantum strains from 19 different zymodemes, which
      were recognized equally. It was also used on human and canine clinical samples.
      PCR-ELISA has a higher sensitivity than the other techniques used (IFAT, parasite
      cultures, optical microscopy of stained samples) and permits detection of a
      minimum of 0.1 promastigotes or 1 fg of genomic DNA. PCR-ELISA can be used to
      diagnose human cutaneous leishmaniasis using material obtained by scraping the
      lesion margin, and human visceral leishmaniasis in HIV(+) individuals and canine
      leishmaniasis with peripheral blood samples. The presence of L. infantum in dogs
      with low antibody titres with IFAT technique (20 and 40) was demonstrated
      indicating that seroprevalence data from epidemiological studies underestimate
      the true rates of infection.

PMID- 11444614
TI  - rDNA phylogeny of Intrapredatorus barri (Microsporida: Amblyosporidae) parasitic
      to Culex fuscanus Wiedemann (Diptera: Culicidae).
AB  - Intrapredatorus barri, a microsporidian parasite of the predator mosquito Culex
      fuscanus Wiedemann has been shown to be heterosporous. In many features this
      species has been reported to be similar to Amblyospora trinus, another
      microsporidian parasite of a different predator mosquito which was thus proposed
      for reassignation to the genus Intrapredatorus. In this report small subunit rDNA
      has been sequenced from I. barri and phylogenetic analysis of 42 microsporidia
      sequences has been performed. The molecular data show that I. barri can not be a
      member of the genus Amblyospora. Furthermore, the phylogenetic analysis shows,
      with high confidence, that the Amblyospora spp. sequences in the present study
      are not monophyletic.

PMID- 11444615
TI  - Unravelling the phylogenetic relationships of African trypanosomes of suids.
AB  - African trypanosomes of the subgenera Nannomonas and Pycnomonas have been
      recorded from both wild and domestic suids. However, complete descriptions of
      some of these trypanosomes with regard to host range, pathogenicity, transmission
      and distribution are still lacking. Neither the recently described Trypanosoma
      (Nannomonas) godfreyi nor Trypanosoma (Nannomonas) congolense Tsavo have been
      isolated from mammalian hosts, while Trypanosoma (Pycnomonas) suis remains the
      rarest of the Salivarian trypanosomes. The only isolate presumed to be of the
      latter species is maintained at the Kenya Trypanosomiasis Research Institute,
      Nairobi. We present here the results of characterization of this isolate by
      morphology, tsetse transmission, the use of species-specific DNA probes and DNA
      sequence analysis. Morphology in stained blood smears revealed a small
      trypanosome with a free flagellum. Experimental transmission through Glossina
      morsitans morsitans showed a developmental cycle typical of subgenus Nannomonas A
      positive identification was obtained with species-specific PCR primers for T.
      congolense Tsavo; moreover, the sequence of the SSU rRNA gene was almost
      identical to that of T. congolense Tsavo on database. In phylogenetic analysis of
      the SSU rRNA genes of Salivarian trypanosomes, T. congolense Tsavo grouped with
      T. simiae rather than T. congolense, suggesting that the name T. simiae Tsavo is
      more appropriate.

PMID- 11444616
TI  - Adults acquire filarial infection more rapidly than children: a study in
      Indonesian transmigrants.
AB  - To dissociate the influence of host age from length of exposure on acquisition of
      filarial infection, we examined the development of microfilaraemia and anti
      filarial IgG4 in all ages of a naive population that became suddenly exposed to
      Brugia malayi as a result of transmigration. Responses in 247 transmigrants, who
      had settled for periods of several months up to 6 years in their new homesteads,
      were compared with those of 133 life-long residents. As shown in earlier studies,
      anti-filarial IgG4 increased with age in the indigenous populations, whose age is
      equivalent to length of exposure. However, by examining transmigrants, it became
      clear that development of specific IgG4 was influenced by age, since levels of
      this antibody were consistently higher in transmigrant adults than in
      transmigrant children, despite an equal length of exposure to filarial infection.
      Examining microfilaraemia, it was confirmed that infection establishes more
      rapidly in adults than in children.

PMID- 11444617
TI  - Determinants for resistance and susceptibility to microfilaraemia in Litomosoides
      sigmodontis filariasis.
AB  - Filarial infections of humans are chronic diseases. Despite an ongoing immune
      response, adult filariae continuously produce their offspring, the microfilariae
      (Mf), which are able to persist in sufficient numbers to ensure transmission. In
      this study, host- and parasite-derived factors, which contribute to persistence
      of Mf, were investigated using the filariasis model of Litomosoides sigmodontis
      in mice. Different strains of mice were found to differ widely in their
      capability to eliminate circulating Mf. Studies of congenic mouse strains showed
      that early and rapid clearance of Mf was mediated by activation pathways relevant
      to innate immunity, whereas late or delayed clearance of Mf was pre-determined by
      MHC-related factors. Genetic knock-out of genes for the MHC class-II molecules
      totally abrogated resistance. Most interestingly, the presence of only I adult
      female, but not male worms, renders all mice susceptible, irrespective of the
      genetic background, enabling Mf to circulate for extended periods of time. Such
      prolonged microfilaraemia was also observed in L. sigmodontis-infected animals
      challenged with heterologous Mf of Acanthocheilonema viteae. The use of cytokine
      gene knock-out mice showed that persistence of L. sigmodontis Mf was facilitated
      by IL-10, but not by IL-4 or IFN-gamma. In conclusion, irrespective of a
      resistant or susceptible host genetic background, survival of Mf of L.
      sigmodontis in mice is decisively regulated by the presence of adult female L.
      sigmodontis which will skew and exploit immune responses to facilitate the
      survival and persistence of their offspring in the infected host.

PMID- 11444618
TI  - Refractoriness of host haemocytes to parasite immunosuppressive factors as a
      putative resistance mechanism in the Biomphalaria glabrata-Echinostoma caproni
      system.
AB  - In contrast to the growing knowledge accumulated on plant resistance to
      pathogens, mechanisms of parasite resistance largely remain to be elucidated in
      animal species. In the present study we investigated mechanisms underlying
      resistance/susceptibility in the snail-trematode system Biomphalaria glabrata
      Echinostoma caproni. In particular, we compared the effect of the parasite
      excretory-secretory (E-S) products on the defence functions of haemocytes from 2
      susceptible and 2 resistant snail strains. In vitro experiments showed that E.
      caproni E-S products inhibit adhesion and phagocytosis of haemocytes from
      susceptible snails. A partial biochemical characterization also suggested that
      the interfering factor(s) is (are) heat-labile glycosylated polypeptides of
      molecular mass between 10 and 30 kDa. Interestingly, haemocytes from resistant
      snails remained unaffected by the parasite E-S products, suggesting that a
      constitutive difference results in their refractoriness to the parasite's
      immunosuppressive factor(s).

PMID- 11444619
TI  - The expression of immunity to Teladorsagia circumcincta in ewes and its
      relationship to protein nutrition depend on body protein reserves.
AB  - We hypothesized that expression of immunity to gastrointestinal nematodes and its
      relationship with dietary metabolizable protein (MP) supply in ewes depended on
      body protein--but not on body fat reserves. Twin-bearing ewes were trickle
      infected with Teladorsagia circumcincta. Three mid-pregnancy feeding treatments
      were used, calculated to maintain body reserves (HH), maintain body protein- and
      lose body fat reserves (HL), or lose body reserves (LL), and followed by 2
      isoenergetic, periparturient feeding treatments, calculated to provide either
      scarce (LP) or adequate (HP) amounts of MP. At the end of the mid-pregnancy
      feeding treatment, HL- and LL-ewes had a smaller backfat depth (approximately
      body fat reserves) than HH-ewes, and LL-ewes had a smaller muscle depth
      (approximately body protein reserves) and higher faecal egg counts (FEC) than HH-
      and HL-ewes. Overall, LL-ewes had higher periparturient FEC than HH- and HL-ewes,
      and LP-ewes had higher periparturient FEC than HP-ewes. However, LL-ewes offered
      the LP feed had higher periparturient FEC than ewes on any of the other
      combinations of feeding treatments. Feeding treatments affected plasma pepsinogen
      but not plasma IgA. The results support the view that body protein- but not body
      fat reserves may overcome consequences of dietary MP scarcity on periparturient
      breakdown of immunity to gastrointestinal nematodes.

PMID- 11444620
TI  - Contrasting regulation of fecundity in two abomasal nematodes of Svalbard
      reindeer (Rangifer tarandus platyrhynchus).
AB  - Stability of trichostrogylid populations indicates that some form of density
      dependent regulation occurs which could act through fecundity. We present
      evidence for intraspecific density-dependent effects in 1 of 2, dominant,
      abomasal nematodes species (Ostertagia gruehneri) of Svalbard reindeer (Rangifer
      tarandus platyrhynchus). We found evidence in O. gruehneri, for density-dependent
      regulation of female worm length in April, July and October 1999. However, it is
      only in July that female worm length explains the variation in the number of eggs
      in utero which is also related to egg production per female worm only in this
      month and not at other times of the year. The seasonal pattern in faecal egg
      output in this species focuses egg production in the summer months when
      conditions are favourable to transmission. In contrast, we found no evidence in
      the other common species (Marshallagia marshalli) for density-dependent
      regulation of female worm length during or the number of eggs in utero. Faecal
      egg output in M. marshalli was positively related to worm burden but not to the
      mean number of eggs in utero. Neither inter-specific interactions nor host body
      condition appeared to influence worm fecundity. The contrasting patterns of
      density-dependent regulation of fecundity provides further evidence for divergent
      life-histories in this nematode community.

PMID- 11444621
TI  - Assessment of benzimidazole binding to individual recombinant tubulin isotypes
      from Haemonchus contortus.
AB  - One a- and 2 beta-tubulin isotypes (isotypes 1 and 2) from the parasitic nematode
      Haemonchus contortus were artificially expressed in E. coli and purified to
      obtain tubulin that was capable of polymerizing into microtubules. Binding of
      [14C] mebendazole (MBZ), a benzimidazole compound, to each individual
      unpolymerized isotype and to microtubules polymerized from recombinant alpha- and
      beta-tubulin was assessed and Kd and Bmax values determined. Mebendazole bound to
      the individual tubulin isotypes with a stoichiometry of 1:1. Binding occurred
      with highest affinity to alpha-tubulin followed by beta-tubulin isotype 2 and
      beta-tubulin isotype 1 indicating that alpha-tubulin may play a role in
      benzimidazole binding to microtubules. Upon polymerization of alpha- and beta
      tubulin isotype 2 into microtubules the stoichiometry of binding increased to 2:1
      (mebendazole : tubulin) while binding affinity remained the same. Mebendazole
      binding to alpha/beta-isotype 1 microtubules remained unchanged following
      polymerization. The increase in the number of benzimidazole receptors on
      alpha/beta-isotype 2 microtubules suggests the formation of a new benzimidazole
      receptor upon polymerization.

PMID- 11444622
TI  - Metapopulation and community dynamics of helminth parasites of eels anguilla
      Anguilla in the River Exe system.
AB  - The possibility that much of the spatial and temporal variation in helminth
      communities in freshwater fish can be explained in terms of metapopulation theory
      was tested by examining helminth component communities of eels sampled from 3
      localities in the River Exe and 5 of its tributaries on 2 occasions at an
      interval of 3 years. Four specific predictions of metapopulation theory in
      relation to community dynamics were tested. The prediction that parasite species
      could be recognized as common and rare and that this was sensitive to scale was
      met. The prediction that core species would be more widely distributed and have a
      higher dispersal ability was met only in part. The prediction that similarity
      between communities would increase with connectivity and decrease with distance
      apart was not met. The final prediction that species would go locally extinct and
      be replaced by rescue effects was not met. There was evidence of local
      extinctions; not of eel specialists but of species using other fish species as
      their principal definitive hosts. Eel helminth communities were heavily dominated
      by 3 species of eel specialists which were relatively stable and responsible for
      most of the similarity and its changes in space and time. It was concluded that
      metapopulation theory did not provide a very satisfactory explanation for the
      changes in the helminth communities in eels and reasons for this included the
      inherent difficulty of applying metapopulation theory to parasites and the fact
      that the helminth communities in eels in the River Exe were atypical in being
      dominated by eel specialists.

PMID- 11444623
TI  - Resistance against migrating ascaris suum larvae in pigs immunized with infective
      eggs or adult worm antigens.
AB  - Resistance to Ascaris suum infections was investigated in 8- and 15-week-old
      Iberian pigs. Groups of 3 or 5 pigs were immunized weekly for 6 weeks with
      antigens of adult A. suum: a 97 kDa body wall (BW) fraction, a 42 kDa fraction of
      pseudocoelomic fluid (PF) or a 14 kDa PF-fraction; or were inoculated with
      increasing doses of infective eggs (500-20,000), with or without abbreviation by
      pyrantel pamoate. All immunized pigs and unimmunized control pigs, were
      challenged with 10,000 infective eggs 7 days after the last immunization. The
      number of liver lesions and lung larvae was substantially lower in the older pigs
      than in the younger ones 7 days after challenge, but the resistance in immunized
      pigs of both age groups was similar in comparison to the challenge controls of
      the same age. The highest degree of resistance against lung larvae was observed
      in pigs immunized with A. suum eggs (97-99%). The pigs immunized with the 14 kDa
      and 42 kDa PF-fractions were also well protected (67-93%), while no protection
      was produced by the 97 kDa BW fraction (0-49%). The reduction of white spots
      following immunization was less evident, with a maximum of 82% reduction in egg
      inoculated young pigs.

PMID- 11444624
TI  - Aging--preparing for the 21 st century.

PMID- 11444625
TI  - Preliminary investigation of the responsiveness of the Melbourne Low Vision ADL
      index to low-vision rehabilitation.
AB  - PURPOSE: To conduct a preliminary investigation on the ability of the Melbourne
      Low Vision ADL Index to detect changes in functional ability as a result of low
      vision rehabilitation. METHODS: Twenty two subjects with age-related macular
      degeneration (ARMD) who were newly referred to the Kooyong Low Vision Clinic were
      recruited. The Melbourne Low Vision ADL Index was administered prerehabilitation
      and postrehabilitation. Changes in scores and effect size statistics were
      analyzed. RESULTS: The median total score for the subjects prerehabilitation was
      67, and the median total score postrehabilitation was 76. The difference in
      prerehabilitation and postrehabilitation scores was statistically significant
      (Wilcoxon signed rank test = 248.5, p < 0.001). The mean change score for the
      total Melbourne Low Vision ADL Index was 9.3 (SD, 5.6). Thus the overall effect
      size statistic (mean change score divided by SD of prerehabilitation score) was
      0.78. CONCLUSIONS: This preliminary investigation indicates that the Melbourne
      Low Vision ADL Index is responsive to a rehabilitation program for patients with
      ARMD. It has potential to be used as a measure of low-vision rehabilitation
      outcomes.

PMID- 11444626
TI  - Loss of visual acuity is the main reason why reading addition increases after the
      age of sixty.
AB  - PURPOSE: To determine why the reading addition increases after the age of 55 to
      60 years when accommodation is zero. METHODS: Distance and near visual acuities,
      arm length, habitual near working distance, reading addition, and pupil diameter
      were measured in 44 subjects aged >60 years (mean, 72.9 +/- 5.7). Reading
      addition values were attained using three techniques: least-plus addition using
      both N-notation text and MN-READ text and the cross-cylinder technique. RESULTS:
      The mean dioptric working distance was 2.75 +/- 0.40 D. The reading addition
      found using N-notation text (+2.21 +/- 0.38 D) was significantly lower than that
      measured using MN-READ text (+2.48 +/- 0.49 D) or the cross-cylinder method
      (+2.53 +/- 0.44 D). The reading addition was positively correlated with the
      dioptric working distance (r = 0.47, p < 0.01), and decreasing habitual working
      distance was associated with poorer visual acuity (r = -0.42, p < 0.01).
      CONCLUSIONS: Our results suggest that decreases in near visual acuity after 60
      years of age lead to a reduction in habitual working distance, which increases
      text angular subtense. In turn, the reduced working distance requires a greater
      reading addition. Increases in depth of field associated with both suprathreshold
      text (N-notation) and lower visual acuity lead to reading additions being less
      than the dioptric working distance.

PMID- 11444627
TI  - A comparison of noninvasive objective and subjective measurements of the optical
      density of human ocular media.
AB  - BACKGROUND: It is important for both researchers and clinicians to know the
      spectral composition of the light that reaches the retina. With this in mind,
      Johnson et al. developed a quick, objective instrument called the Lens Absorption
      Monitor (LAM) to measure the attenuation of light by the ocular media. Using a
      more refined method of measuring and correcting for scatter, we compared the
      results of the LAM against those with a subjective method utilizing a bipartite
      scotopic brightness-matching procedure (BIP). METHODS: We tested 41 healthy
      subjects (mean age, 35.9 years) with the LAM and BIP. RESULTS: Intereye
      correlation coefficients for the LAM were 0.70 at 410 nm and 0.83 at both 430 and
      450 nm; for BIP, intereye correlation coefficients were 0.56 at 410 nm, 0.42 at
      430 nm, and 0.38 at 450 nm. For optical density as a function of age, there was
      no statistically significant difference between the two instruments at 410 nm in
      either the slope (p > 0.43) or y intercept (p > 0.75). However, at both 430 and
      450 nm, there was a significant difference in both slope (p < 0.001) and y
      intercept (p < 0.05) for the two instruments. CONCLUSIONS: With the latest
      refinements, LAM density measures correlated well with BIP estimates at 410 nm,
      but not at 430 or 450 nm. This underscores the fact that the LAM measures the
      spectral density of the anterior segment, whereas the BIP method is a measure of
      all the ocular media except for macular pigment. The difference between these two
      measures is consistent with the existence of a prereceptoral, presumably
      intraretinal, pigment (or pigments) located outside the anatomic fovea that
      absorbs light at short wavelengths.

PMID- 11444628
TI  - Aging of the optics of the human eye: lens refraction models and principal plane
      locations.
AB  - Biometric data describing the geometry and spacings of emmetropic human eyes were
      combined with lens shape and placement within the globe to generate paraxial
      models of image formation as a function of age. Three different representations
      of the shape of the internal refractive index gradient of the lens were evaluated
      -a Gullstrand-type model consisting of cortical and nuclear regions with
      different refractive indices, a power series model, and a linear-gradient model.
      All three refractive models satisfy the requirements for focus for all the data
      sets, indicating that lenticular refractive index gradient shape is essentially
      underdetermined in the paraxial limit. Lens refractive power decreases by almost
      2 D during a 50-year period, and the concomitant decrease in system refractive
      power is due almost entirely to this effect. The reduction in spacing between the
      lens principal planes is a function of this, as is their anterior movement with
      age, and suggests that the compensatory processes maintaining far focus at the
      expense of near are not exactly balanced. Despite these changes in the lens
      contribution and their effect on the location of the system principal planes,
      which also move anteriorly, the spacing between the system principal planes
      remains constant. However, the trend toward reduced overall system power with age
      indicates the primary role of the lens in mediating image formation onto the
      retina over time.

PMID- 11444629
TI  - Theoretical analysis of accommodation amplitude and ametropia correction by
      varying refractive index in Phaco-Ersatz.
AB  - Phaco-Ersatz is a surgical procedure for restoring accommodation in which the
      presbyopic crystalline lens is replaced by a flexible polymer gel in the lens
      capsule. We assessed the feasibility of simultaneously correcting ametropia while
      restoring accommodation using Phaco-Ersatz by utilizing polymer gel of the
      appropriate refractive index. Computation results using paraxial equations and
      ray tracing on two model eyes indicate that although this approach might be
      feasible for the hypermetrope, its usefulness for correcting myopia is limited,
      principally due to significant reductions in the resultant amplitude of
      accommodation.

PMID- 11444630
TI  - The thickness of the aging human lens obtained from corrected Scheimpflug images.
AB  - Commonly, measurements of lens thickness are performed using A-scan
      ultrasonography or slitlamp Scheimpflug photography. Both techniques have their
      drawbacks in the study of presbyopia: ultrasonography requires the velocity of
      sound in the lens which may change with age, whereas Scheimpflug photography
      requires knowing the refractive index of the lens to enable correction of the
      photographs for the distortion due to the refraction of the cornea and lens. By
      combining Scheimpflug photography and axial optical eye-length measurements, we
      were able to individually correct the Scheimpflug images for distortion and
      calculate the refractive index and thickness of the human lens. Lens thickness of
      90 subjects ranging in age between 16 and 65 years was measured, and an average
      increase of 24 microm/year was found. This value is consistent with
      ultrasonographic measurements assuming an age-independent velocity of sound in
      the lens of 1641 m/s. The posterior lens surface recedes from the cornea with
      age, and this backward movement does not differ significantly from the forward
      movement of the anterior lens surface.

PMID- 11444631
TI  - Ultrasound biomicroscopy of the aging rhesus monkey ciliary region.
AB  - Ultrasound biomicroscopy of the living rhesus monkey ocular ciliary region was
      undertaken to identify age-dependent changes that might relate to the progression
      of presbyopia. Monkeys were anesthetized and pharmacologically cyclopleged, the
      eyelids were held open with a lid speculum, and sutures were placed beneath the
      medial and lateral rectus muscles. Ultrasound biomicroscopy imaging of the nasal
      and temporal quadrants of the eye were performed, and the live images were
      recorded to videotape. Subsequent image analysis was performed to obtain
      objective morphometric measurements of the ciliary body region. The ciliary body
      inner radius of curvature, outer radius of curvature, inner arc length, area,
      thickness, perimeter, zonular fiber length, and circumlental space were measured.
      Zonular space was calculated. The circumlental space decreased with increasing
      age in the temporal quadrant. The other morphologic measurements were not
      significantly correlated with age or body weight. Most morphologic measurements
      were significantly different comparing temporal vs. nasal quadrants. Bifurcation
      of the posterior zonular fibers was frequently observed. Although temporal
      circumlental space was the only measurement found to change with age, ultrasound
      biomicroscopy of the living rhesus ciliary region did identify distinct nasal vs.
      temporal asymmetries, which may reflect anatomical requirements for convergence
      associated accommodation.

PMID- 11444632
TI  - Age-related changes in the mouse outer retina.
AB  - PURPOSE: To define the physiological and structural changes that may accompany
      aging in the normal mouse retina. METHODS: C57BL/6 mice were maintained under
      cyclic light for either 2, 6, or 12 months. After rod- and cone-mediated corneal
      electroretinograms (ERG's) were recorded from anesthetized animals, the retinal
      structure was quantitatively examined. Photoreceptor cell density was measured
      within 100-microm regions of the central superior and inferior retina. Cone
      photoreceptor subtypes were identified by immunocytochemistry. RESULTS: The
      amplitudes of rod- and cone-mediated ERG's were reduced in older mice, although
      the overall ERG wave-form did not change appreciably and implicit times were not
      changed in an age-dependent fashion. In comparison, there was no significant age
      related decline in rod or cone photoreceptor density. CONCLUSIONS: The amplitude
      of the mouse ERG declines with age. This change does not appear to reflect a
      change in the structural integrity of the photoreceptor cells. In functional
      studies of murine models of late-onset retinal disorders, it will be important to
      take these changes into consideration.

PMID- 11444633
TI  - Age-related topographical changes in the normal human optic nerve head measured
      by scanning laser tomography.
AB  - PURPOSE: This study was designed to investigate the effects of advanced aging on
      the optic nerve head (ONH) structure and retinal nerve fiber layer (RNFL)
      thickness in the eldest segment of our population. METHODS: Twenty-seven healthy
      elderly subjects between 75 and 88 years of age (average, 80.1 +/- 0.83 years)
      and 30 healthy younger subjects between 20 and 32 years of age (average, 23.1 +/-
      0.50 years) were recruited for a cross-sectional comparison between ONH
      morphology and RNFL thickness as measured by scanning laser tomography. The ONH
      disc, cup, and rim areas; cup-to-disc ratio; and the mean thickness of the RNFL
      were quantified. RESULTS: The cup and disc areas as well as the cup-to-disc area
      ratio increased with age, whereas the RNFL thickness decreased during the course
      of normal senescence. CONCLUSIONS: Any diagnoses of ocular pathology in the
      elderly must differentiate the effects of normal aging on the ONH topography and
      RNFL thickness. To that effect, the present study provides a clinical profile of
      ocular structures that extend into the oldest geriatric age group.

PMID- 11444634
TI  - Senescent changes of the normal visual field: an age-old problem.
AB  - PURPOSE: To examine the effect of normal aging on visual field sensitivity and
      identify the best-fitting function for normal populations. METHODS: Full
      Threshold standard automated perimetry data (program 24-2, Humphrey Field
      Analyzer) was collated retrospectively from clinically normal subjects who had
      previously been recruited for studies of normal visual function. One eye of each
      subject was randomly selected for analysis. Linear, bilinear, and simple
      nonlinear candidate functions of mean sensitivity vs. age (independent variable)
      were applied to these cross-sectional population data. Differences in the aging
      effect by eccentricity and hemifield were also considered. RESULTS: Data from 562
      normal eyes were available for analysis. A significant negative relationship
      existed between age and mean visual field sensitivity within the cross-sectional
      population data. Coefficients of determination for the linear, bilinear, and
      nonlinear functions were 0.21, 0.20, and 0.26, respectively, indicating that the
      nonlinear function provided best characterization of the effect of age on mean
      sensitivity. A small but significant increase in the aging effect was present
      both peripherally (p < 0.001) and superiorly (p < 0.001). DISCUSSION: The
      nonlinear function that provided the best fit to cross-sectional population data
      indicates that age exerts an increasing effect on perimetric sensitivity with
      age, which has implications for clinical devices that use linear age coefficients
      to correct for normal aging effects. A linear age correction will overestimate
      aging changes for younger subjects and, therefore, may miss early pathologic
      changes in visual sensitivity. Conversely, linear age correction will also
      underestimate aging changes for older subjects and, thus, may overcall
      pathological sensitivity loss in this group. The effect of age within subjects
      requires further investigation to provide reliable estimates of the effect of age
      on sensitivity.

PMID- 11444635
TI  - Aging of the chromatic onset visual evoked potential.
AB  - PURPOSE: To examine changes in the chromatic onset visual evoked potential (VEP)
      as a function of aging. METHODS: VEP's were measured in response to chromatic
      sinusoidal gratings (1.0 and 0.5 cpd), selectively chosen to modulate the L-M
      channel and S - (L+M) channel and presented in onset-offset mode. Responses to
      achromatic gratings presented in a reversal mode were also measured. Twenty
      subjects were tested, ranging in age from 21 to 93 years. RESULTS: Unlike changes
      observed earlier in life, the general shape of the chromatic onset wave-form
      changed little with age; however, latencies increased significantly as a function
      of age. Amplitude changes revealed a decreasing trend that was not statistically
      significant. There was little change in the achromatic responses with age.
      CONCLUSIONS: Our results demonstrate a systematic slowing of the chromatic onset
      VEP with age. The gradual nature of the latency changes and the lack of dramatic
      and complex wave-form shape changes may allow development of age-based normative
      data for use in clinical settings.

PMID- 11444636
TI  - Effects of aging on shape discrimination.
AB  - A large number of senior patients manifest eye diseases in addition to normal
      aging changes in their visual system. Visual tests not affected by age would be
      very useful in early detection of age-related eye diseases. The purpose of this
      study was to determine the effects of aging on the detection of contour
      deformation. Seventy-six normal subjects were divided into three age groups:
      young adults 15 to 39 years old (N = 26); middle-aged adults 40 to 59 years old
      (N = 22); and senior adults 60 to 78 years old (N = 28). Stimuli were circular or
      linear D4 (4th derivative of Gaussian) contours. A spatial two-alternative forced
      choice staircase paradigm was used. In each trial, one deformed and one
      undeformed contour were presented on a screen. Subjects indicated which contour
      was deformed. Deformation detection thresholds were estimated by a maximum
      likelihood fitting procedure. We found that at a low modulation frequency (four
      cycles), the performance of detecting deformation does not change with age, and
      it does not correlate with either visual acuity or letter contrast sensitivity.
      At a higher modulation frequency (eight cycles), a significant difference between
      mean thresholds was found for young and senior adults. For circular D4, the mean
      threshold was elevated by 18%, from 7.6 sec arc (young adults) to 9.0 sec arc
      (senior adults). For linear D4, the mean threshold was elevated by 52%, from 5.8
      sec arc to 8.8 sec arc. As a comparison, minimum angle of resolution was
      increased by 33%, and letter contrast threshold was elevated by 81%. The
      performance for linear D4 at higher modulation frequency was found to be
      significantly correlated with contrast threshold. These results provide further
      evidence to support the hypothesis that different mechanisms may be underlying
      the detection of circular and linear D4 contour deformation. The very small
      effect of aging on hyperacuity for radial deformation suggests that a global
      shape discrimination task could be a sensitive test for quantifying the early
      visual loss caused by eye diseases among seniors.

PMID- 11444637
TI  - The effects of six months of contact lens wear on the tear film, ocular surfaces,
      and symptoms of presbyopes.
AB  - PURPOSE: To assess the tear film, ocular surfaces, and symptoms of ocular
      discomfort in a presbyopic population before and after contact lens wear.
      METHODS: A total of 150 presbyopes (49% were previous soft contact lens wearers)
      participated in a clinical trial in which they wore either monovision (single
      vision Acuvue lenses) or Acuvue Bifocal contact lenses. Clinical measurements of
      tear film, biomicroscopy, and corneal sensitivity as well as subjective ratings
      using the Dry Eye Questionnaire were collected at the initial visit and repeated
      after 6 months. Comparisons were made between age groups (40 to 51 years and 52
      to 71 years) and genders before and after contact lens wear. Associations between
      objective and subjective tests were sought. RESULTS: After 6 months of contact
      lens wear, clinical signs had worsened by less than one-half of a grade, and tear
      break up time (TBUT) worsened by 3 s. Only TBUT was lower for the older age
      group. Females had less bulbar hyperemia, more sensitive eyes, more lissamine
      green staining, and lower TBUT and phenol red thread measurements (all p < 0.04).
      Twenty-eight percent experienced dryness before contact lens wear, but this
      figure increased to 68% when wearing contact lenses. There were no age
      differences, but almost twice as many females as males reported dryness.
      Reporting symptoms of dryness was associated with gender, corneal sensitivity,
      and type of corneal staining. CONCLUSIONS: These results provide a representation
      of the ocular surface condition and symptoms of ocular discomfort in the middle
      aged population and seem similar to reports of younger populations. Wearing
      contact lenses seems to influence dry eye symptoms more than age or gender.
      Therefore, presbyopes should not be excluded from consideration for contact lens
      fitting.

PMID- 11444638
TI  - Publications and conflict of interest.

PMID- 11444639
TI  - A critical review of clinical trials for low-molecular-weight heparin therapy in
      unstable coronary artery disease.
AB  - Unstable angina and non-ST-segment elevation myocardial infarction (MI) are
      collectively referred to as unstable coronary artery disease (UCAD). They are
      conditions that share a common pathophysiology and represent frequently
      encountered, potentially life-threatening clinical manifestations of advanced
      atherosclerosis. Therefore, treatment of UCAD is a major focus for practicing
      clinicians, and although pharmacologic agents have been developed that impact on
      patient outcome, recent data suggest that a further reduction in ischemic
      complications is possible. Acute-phase treatment with aspirin is associated with
      a significant reduction in death and nonfatal MI in patients with UCAD. This
      benefit is enhanced by the addition of unfractionated heparin (UFH) to the
      treatment strategy; however, UFH requires careful monitoring and titration. In
      contrast, low-molecular-weight heparins (LMWHs), produced by chemical or
      enzymatic depolymerization of UFH, yield a predictable and consistent
      pharmacokinetic profile and anticoagulant response, making them an attractive
      treatment alternative to UFH in patients with UCAD. The optimal duration of
      treatment with LMWH is an important question influenced by the observation that
      reactivation of coagulation occurs following the early and abrupt discontinuation
      of heparin treatment. Early trials, such as FRISC and FRIC, demonstrated the
      benefit of acute therapy with dalteparin sodium; however, the results of extended
      treatment with dalteparin were inconclusive. The extended phase of these studies
      included relatively low-risk patients, and a once-daily, relatively low-dose
      strategy was employed. The findings derived from the FRISC II trial, which used a
      twice-daily dose of dalteparin, suggest a benefit for at least 60 days with
      extended treatment in high-risk patients with UCAD. Although an early-invasive
      treatment strategy is particularly beneficial, patients in whom early
      revascularization is not possible should be considered for extended treatment
      with dalteparin for up to 45 days, especially those awaiting percutaneous
      coronary intervention. Extended treatment with dalteparin therefore provides a
      protective "bridge" to enhance the outcome of patients with UCAD awaiting
      revascularization.

PMID- 11444640
TI  - Successful external cardioversion of atrial fibrillation in patients referred to
      an electrophysiologist for internal cardioversion.
AB  - BACKGROUND: Internal cardioversion of atrial fibrillation with direct current
      energy has become an increasingly employed technique for patients who fail
      external cardioversion. HYPOTHESIS: The purpose of this study was to determine
      whether internal cardioversion could be avoided by careful attention to
      cardioversion technique in a group of patients referred specifically for internal
      cardioversion after failed external cardioversion by community cardiologists.
      METHODS: We performed external cardioversion utilizing two operators applying
      significant pressure to the thorax with up to 360 J prior to the planned internal
      cardioversion in 20 patients referred for internal cardioversion after failed
      attempts at external cardioversion. RESULTS: Sixteen patients (80%) were
      successfully cardioverted and avoided the risk, inconvenience, and cost of
      internal cardioversion. CONCLUSION: External cardioversion with significant
      anterior paddle pressure by two operators can decrease the need for internal
      cardioversion in a significant portion of patients referred to
      electrophysiologists for internal cardioversion and should be considered prior to
      an invasive procedure.

PMID- 11444641
TI  - C-reactive protein is a marker for a complex culprit lesion anatomy in unstable
      angina.
AB  - BACKGROUND: The putative theory is that the clinical syndrome of unstable angina
      is caused by rupture of the atherosclerotic plaque with superimposed thrombus
      formation. It is characterized by angiographically complex coronary lesions in
      the majority of patients. HYPOTHESIS: This study aimed at assessing the
      correlation between C-reactive protein (CRP) and the complexity of culprit
      coronary lesions in unstable angina. METHODS: We identified culprit lesion
      complexity in 96 patients with unstable angina and normal creatine kinase (CK)
      and CK-MB mass. Serum concentrations of CRP (N < 5.0 mg/l) and cardiac troponin T
      (cTnT; N < 0.1 ng/ml) were measured on admission. RESULTS: There was a trend
      toward a higher grade of anatomical complexity of the culprit lesion in patients
      with elevated CRP (p = 0.007) and cTnT levels (p = 0.027). Patients who had
      intermediate- or high-grade lesion severity had a higher level of CRP (8.5 +/-
      5.7 mg/l) and cTnT (0.118 +/- 0.205 ng/ml) on admission than those who had normal
      or low-grade lesions (5.7 +/- 4.0 mg/l, 0.017 +/- 0.021 ng/ml, respectively);
      Mann-Whitney U, p = 0.002 and p < 0.001, respectively. Furthermore, the
      likelihood of having intermediate- or high-grade complexity of the culprit lesion
      was higher when CRP levels were elevated in all patients (p = 0.007, odds ratio
      [OR] = 4.286; 95% confidence interval [CI] 1.492-12.310) and in those with normal
      cTnT levels (p = 0.025, OR = 3.876; 95% CI 1.185-12.678). Also, higher CRP levels
      strongly correlated with the need for revascularization interventions (p <
      0.0005). CONCLUSION: Elevated CRP level on admission is a marker for anatomic
      complexity of culprit lesions and need for revascularization interventions in
      unstable angina.

PMID- 11444642
TI  - N-acetylcysteine improves microcirculatory flow during smoking: new effects of an
      old drug with possible benefits for smokers.
AB  - BACKGROUND: Cigarette smoking provokes marked acute changes in the
      microcirculatory vasculature, including a reduced blood flow velocity. In
      accordance with the hypothesis that the reduced blood flow is due to an imbalance
      between pro-oxidants and oxidants, we recently showed that most of the reduction
      could be reversed by a high dose of vitamin C. HYPOTHESIS: In the present work we
      tested the hypothesis that N-acetylcysteine, a mucolyticum and an antioxidant,
      may have an effect on the smoking-induced changes observed by vital capillary
      microscopy of the nailfold. METHODS: In all, 37 healthy volunteers of both
      genders and with varied smoking habits were treated with N-acetylcysteine 200 mg
      t.i.d. for 2 weeks. In vivo investigation of the microcirculation by
      capillaroscopy was performed before and after treatment. RESULTS: Treatment with
      N-acetylcysteine significantly reduced the smoking-induced relative decrease in
      capillary blood flow velocity in a group of volunteers with varied smoking habits
      (p = 0.0016). The preventive effect was clearly significant in smokers (p =
      0.003). CONCLUSION: Treatment with N-acetylcysteine has a positive impact on
      microcirculatory flow during smoking, particularly in habitual smokers.

PMID- 11444643
TI  - A double-blind, multicentered study comparing the accuracy of diagnostic markers
      to predict short- and long-term clinical events and their utility in patients
      presenting with chest pain.
AB  - BACKGROUND: Millions of patients present annually with chest pain, but only 10%
      have myocardial infarction (MI). We recently reported comparative sensitivity and
      specificity of available markers in the diagnosis of MI; however, optimum
      interpretation of marker results requires prognostic follow-up data. HYPOTHESIS:
      The study was undertaken to study the accuracy of CK-MB subforms, troponin I and
      T, myoglobin, and CK-MB in predicting clinical events at 30 days and 6 months.
      METHODS: In all, 955 consecutive patients with chest pain were enrolled in a
      prospective, multicenter, double-blind study to test the prognostic accuracy of
      these markers. RESULTS: Myocardial infarction was diagnosed in 119 by CK-MB mass
      criteria and unstable angina (UA) in 203 patients by clinical criteria. Follow-up
      at 30 days and 6 months was available in 824 and 724 patients, respectively, with
      mortalities of 2.8 and 4.14%, respectively. Cumulative 6-month mortality was 5.6%
      in MI, 4.4% in UA, and 3.0% in others. Revascularization was reported in 9.3% of
      patients by 6 months. A positive test on each of the markers except myoglobin was
      predictive of revascularization. The composite endpoint of death or
      revascularization occurred in 107 patients by 6 months and a positive result on
      each of the markers was predictive of this composite endpoint (p < 0.05). The
      relative risk of death or revascularization for patients who did not have MI but
      tested positive on each of the markers was > 1.0 but did not reach statistical
      significance. CONCLUSIONS: With the possible exception of myoglobin, each of the
      diagnostic markers displayed similar prognostic performance in patients with
      chest pain presenting to emergency departments. The most appropriate markers to
      triage patients with chest pain, which has both adequate early diagnostic
      sensitivity and prognostic accuracy, are the CK-MB subforms.

PMID- 11444644
TI  - Ibutilide: efficacy and safety in atrial fibrillation and atrial flutter in a
      general cardiology practice.
AB  - BACKGROUND: Published experience with ibutilide (IB) in randomized clinical
      trials reveals that conversion to sinus rhythm (SR) occurs in 31% of patients
      with atrial fibrillation (AF) and in 63% of patients with atrial flutter.
      HYPOTHESIS: The study was undertaken to test the efficacy and safety of IB in
      patients with AF and with atrial flutter and to compare them with those reported
      in previous studies. METHODS: In a general cardiology practice, 54 consecutive
      patients with AF or atrial flutter, no contraindication to IB, and a normal QTc
      interval, were treated with intravenous IB (0.4-2.0 mg). Duration of arrhythmia,
      left atrial (LA) size, ejection fraction (EF), time to conversion, QTc interval,
      and adverse drug events were determined. Patients were observed for a minimum of
      6 h. Successful cardioversion was defined as arrhythmia termination within 6 h.
      RESULTS: Twenty-four of 34 (70.6%) patients with AF and 15 of 20 (75%) patients
      with atrial flutter converted to SR. Conversion of AF to SR was more likely to
      occur if duration of AF was approximately 96 h compared with > 96 h (81 vs. 17%,
      respectively; p = 0.006). The mean time to arrhythmia termination was 68.8 min.
      Left atrial size, determined by echocardiogram, was 44 +/- 13 mm in 43 patients.
      Patients with LA size approximately 45 mm had a conversion rate of 55% in both AF
      and flutter, compared with a conversion rate of 72% in patients with LA size < 45
      mm. Ejection fraction was not a predictor of drug success. The QTc intervals were
      significantly prolonged after IB administration, with a mean change of 47.1 ms
      for successfully treated patients. Sustained polymorphic ventricular tachycardia
      occurred in one patient within 1 min of IB infusion, requiring electrical
      cardioversion to SR. This patient's serum electrolytes and QTc interval were
      normal prior to IB infusion; however, the QTc increased by 160 ms (from 387 to
      547 ms) during drug infusion. No systemic or pulmonary emboli occurred.
      CONCLUSION: The efficacy of IB for conversion of AF to SR in this prospective
      observational study was considerably better than previously reported. Duration of
      AF remains an important predictor of conversion to SR. Complications are rare and
      without long-term adverse effects.

PMID- 11444645
TI  - Images in cardiology. Permanent pacemaker implantation via a persistent left
      superior vena cava.

PMID- 11444646
TI  - Christiaan Neethling Barnard.

PMID- 11444648
TI  - Newer HMG-CoA reductase inhibitor (statin) therapies.
AB  - Although most patients can achieve their National Cholesterol Education Program
      goal with a reduction of < or =30% in low-density lipoprotein cholesterol (LDL-C)
      levels available with all statins, some patients need greater LDL-C lowering.
      Furthermore, new study data suggest that greater clinical event reduction may be
      obtained with more aggressive LDL-C lowering and/or with treatment of factors
      beyond LDL-C. New formulations of statins. including extended-release
      preparations, are achieving greater reductions in LDL-C levels as well as
      favorable modification of high-density lipoprotein cholesterol and triglyceride
      concentrations while maintaining an excellent safety profile.

PMID- 11444649
TI  - Genetic markers for coronary heart disease.
AB  - Coronary heart disease (CHD) is a complex disease that is affected by
      environmental as well as genetic factors. Research is ongoing that probes the
      relationship of human genetic variation to disease, potentially leading to better
      diagnosis and therapy. Variation in factors such as low-density lipoprotein
      cholesterol, apolipoprotein E, high-density lipoprotein cholesterol,
      apolipoprotein A-I/CIII/A-IV, lipoprotein lipase, cholesteryl ester transfer
      protein, lipoprotein (a), and homocysteine may affect CHD risk via genetic or
      environmental mechanisms or their interactions.

PMID- 11444650
TI  - Statins: a brief summary.
AB  - Despite a totality of evidence indicating clear benefits of statin therapy in
      secondary and primary prevention of cardiovascular disease (CVD), a large number
      of additional trials are currently planned or in progress to help us better
      understand, treat, and prevent CVD. Both monotherapy and combination statin
      regimens are being studied to optimize treatment of the total patient and to
      assess mechanisms and benefits of various components of the total lipid profile.

PMID- 11444651
TI  - Current perspectives on lipid lowering with statins to decrease risk of
      cardiovascular disease.
AB  - Although guidelines for individual risk factors for cardiovascular disease (CVD)
      assist the healthcare provider, management of the global risk profile of patients
      is the optimal means to minimize risk. Regardless of whether patients have one or
      more risk factors, elevated lipid values are generally considered to be a major
      contributor to global CVD risk. Therefore, reduction of lipid levels is one of
      the most effective methods to reduce risk of CVD. The 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase inhibitor class of drugs (also known as statins) has
      documented clinical benefits for reducing the incidence of myocardial infarction,
      stroke, death from CVD, and total death. Despite widespread acknowledgment of the
      very favorable benefit-to-risk ratio of the statins, most at-risk patients either
      are not being treated or are not at the goals defined by the National Cholesterol
      Education Program.

PMID- 11444652
TI  - Treating mixed dyslipidemias: why and how.
AB  - Patients with only mildly elevated low-density lipoprotein cholesterol values but
      low high-density lipoprotein cholesterol (HDL-C) and/or high triglyceride levels
      are at high risk for cardiovascular disease. 3-Hydroxy-3-methyl-glutaryl-coenzyme
      A reductase inhibitors (also known as statins) have been shown to slow coronary
      heart disease (CHD) progression, reduce CHD events in patients with low HDL-C
      levels, and raise HDL-C concentrations in patients with mixed dyslipidemias.
      Some, but not all trials of fibrates have shown benefit in patients with low HDL
      C levels. Combination therapy with a statin plus either a fibrate or niacin is
      effective in improving the entire lipid profile, but may increase cost and side
      effects.

PMID- 11444653
TI  - Fatal pediatric head injuries caused by short-distance falls.
AB  - Physicians disagree on several issues regarding head injury in infants and
      children, including the potential lethality of a short-distance fall, a lucid
      interval in an ultimately fatal head injury, and the specificity of retinal
      hemorrhage for inflicted trauma. There is scant objective evidence to resolve
      these questions, and more information is needed. The objective of this study was
      to determine whether there are witnessed or investigated fatal short-distance
      falls that were concluded to be accidental. The author reviewed the January 1,
      1988 through June 30, 1999 United States Consumer Product Safety Commission
      database for head injury associated with the use of playground equipment. The
      author obtained and reviewed the primary source data (hospital and emergency
      medical services' records, law enforcement reports, and coroner or medical
      examiner records) for all fatalities involving a fall. The results revealed 18
      fall-related head injury fatalities in the database. The youngest child was 12
      months old, the oldest 13 years. The falls were from 0.6 to 3 meters (2-10 feet).
      A noncaretaker witnessed 12 of the 18, and 12 had a lucid interval. Four of the
      six children in whom funduscopic examination was documented in the medical record
      had bilateral retinal hemorrhage. The author concludes that an infant or child
      may suffer a fatal head injury from a fall of less than 3 meters (10 feet). The
      injury may be associated with a lucid interval and bilateral retinal hemorrhage.

PMID- 11444654
TI  - The role of the gut in the pathogenesis of death due to hyperthermia.
AB  - Pathologic data from the gastrointestinal tract in heat-stroke victims, although
      documented, are confusing. The object of this study was to document the
      gastrointestinal changes observed during induced total body hyperthermia (42
      degrees C) followed by cooling. An established heat-stroke model was used in a
      university animal laboratory. Group A underwent immersion hyperthermia for 1
      hour, followed by cooling to normothermia. Group B underwent hyperthermia to
      cardiac arrest, followed by resuscitation plus cooling to normothermia. The
      postmortem findings in the gastrointestinal tract were evaluated. In group A,
      several hours after return to normothermia and stable vital signs, delayed
      secondary deterioration with massive gastrointestinal bleeding occurred. The
      postmortem findings revealed bleeding into the whole intestine and
      serosanguineous fluid in the peritoneal cavity. In group B, an adynamic gut was
      observed after 165 +/- 21 minutes (range 125-174) of heating when mean arterial
      pressure (MAP) decreased to 38 +/- 21 mm Hg (range 30-70). Cardiac arrest
      occurred at 178 +/- 26 minutes (range 140-208) of immersion. Eight monkeys could
      be resuscitated to spontaneous circulation with return of normal gut motility,
      then they rearrested at 158 +/- 68 minutes (range 45-228). The postmortem
      findings resembled those in group A. The Postmortem findings in the four monkeys
      in which restoration of spontaneous circulation failed, revealed only some
      intestinal wall edema and occasional petechial hemorrhages. It is concluded that
      after a hyperthermic event, tissue injury continues to develop. The pathologic
      findings are related to the time lapse between hyperthermia, cooling, and death.
      The similarity to the descriptions of septic shock, multiple organ failure, and
      the gut reperfusion syndrome is striking. An immunologic response as a mechanism
      for all these syndromes is discussed.

PMID- 11444655
TI  - Case report of sudden death after a blow to the back of the neck.
AB  - A 13-year-old girl experienced a fall during gym class that caused immediate
      unresponsiveness and death. The lone witness reported that the decedent lost her
      balance as she approached a hurdle and fell, striking her head on a crossbar of
      the hurdle near the ground. Autopsy revealed no external injury. Internal injury
      that could be demonstrated anatomically was confined to a contusion within the
      right semicapitis muscle at the base of the skull. In the absence of an anatomic
      cause of death, possible explanations of the death include a cardiac dysrhythmia,
      a vasovagal stimulus, and diffuse axonal injury caused by a concussive force to
      the junction of the medulla and spinal cord. Animal studies have shown that
      severe concussion can cause death via profound autonomic dysfunction without
      leaving anatomic evidence of injury, and that the essential component of
      concussion is an element of rotational injury to the brain. The authors believe
      that the blow to the neck caused this death by the transmission of a concussive
      force through the reticular activating system. The prompt work of police in
      distinguishing the lone witness from several people in the area who thought they
      knew what had happened was essential for diagnosis. On reaching our conclusions,
      the authors notified first the family, then the superintendent of the school
      system, and finally the news media. The authors told each party in turn that they
      would be contacting the others.

PMID- 11444656
TI  - Sudden cardiac death and right ventricular dysplasia.
AB  - Right ventricular cardiomyopathy dysplasia, now a well-established clinical and
      morphologic entity, was first reported in the medical literature in 1982. The
      cases of sudden death of two young men are here reported, with macroscopic and
      histologic findings. The anatomical explanation of such death was a fibrotic,
      lipomatous, or fibrolipomatous replacement and infiltration of the myocardium of
      the right ventricle. It is suggested that death due to right ventricular
      cardiomyopathy seems to be the result of electrical instability of right
      ventricular myocardium. There were no congenital malformations such as septal
      defect or valvular deformity. The subjects' heart weights were normal. Signs of
      myocardial degeneration and necrosis with or without inflammatory infiltrates
      were not identified.

PMID- 11444657
TI  - Simultaneous sudden infant death syndrome: a proposed definition and worldwide
      review of cases.
AB  - Epidemiologic studies of sudden infant death syndrome (SIDS), the leading cause
      of death of infants during the postperinatal period (7-365 days), have mainly
      focused on the deaths of single infants. Simultaneous sudden infant death
      syndrome (SSIDS), the death of a pair of twins occurring at the same time, has
      received limited attention within the medical community. To the authors'
      knowledge, this article is the first to describe the 41 SSIDS cases cited in the
      world literature from 1900 to 1998 by the location of death, a summary of the
      circumstances surrounding the deaths, and evaluation of these cases in terms of a
      proposed definition of SSIDS. This evaluation critiques whether the 41 pairs of
      SSIDS cases adhere to a newly proposed definition of SSIDS. Twin infant deaths
      must meet all three criteria to be considered SSIDS. The study found that only 12
      pairs of twins met all three criteria (29.2%), nine pairs met two criteria
      (21.9%), alternative cause of death was offered in five pairs of twins (12.1%)
      and in the remaining 15 pairs (36.6%), only limited information was available;
      therefore, no conclusions could be reached.

PMID- 11444658
TI  - Simultaneous sudden infant death syndrome: a case report.
AB  - The first reported case of simultaneous sudden infant death syndrome (SSIDS) in
      Allegheny County, Pennsylvania, occurred on February 27, 1998. Two-month-old
      black fraternal twin girls were both found dead in their crib at the same time.
      After an in-depth death scene investigation, police investigation, toxicologic
      analysis, and complete autopsies, a specific cause of death could not be
      identified. The deaths of the two girls were therefore ruled simultaneous sudden
      infant death syndrome.

PMID- 11444659
TI  - Report on the 2003 revision of the U.S. Standard Certificate of Death.
AB  - The National Center for Health Statistics (NCHS) is responsible for publishing
      Standard Certificates of Birth and Death for the United States of America. The
      standard certificates are revised roughly every 10 years. The revision process is
      designed to ensure that the standard certificates meet, as nearly as possible,
      the use for which they are intended at all levels: individual, local, state, and
      federal. The authors report on the most recent revision of the U.S. Standard
      Certificate of Death, recording the process and the role of the National
      Association of Medical Examiners in the process. Changes recommended during
      revision include requesting known aliases of a decedent and rearrangement of the
      certificate to provide more room for those items requesting dates and for
      describing how the injury occurred. New items have been added asking for
      information regarding traffic fatalities, the role of tobacco use in causing
      death, and whether female decedents were pregnant. Once approved by the
      Department of Health and Human Services, the new standard certificate will be
      made available to the states. Each state will have 2 years to adapt the U.S.
      Standard Certificate of Death to its use and to implement new state death
      certificates on January 1, 2003.

PMID- 11444660
TI  - Saddam's revenge: a post-Gulf War casualty.
AB  - Artillery weapons are designed to inflict death and destruction by way of
      fragmentary and blast injuries. As pieces of modern machinery, they are also
      capable of causing serious injury by their very complex nature. The authors
      present a case analysis of an artillery piece that caused a projectile death
      without a shell.

PMID- 11444661
TI  - Basic instinct in a feline.
AB  - Reported cases in Europe of large felines attacking humans are rare. Recently, in
      France, a man was attacked in an animal park by a tigress he had raised. He
      received fatal cervical wounds. This case of death by bites and lacerations,
      together with others in the recent international literature, underline the
      hereditary ferocity of such felines and the way in which they prefer to inflict
      lesions to the neck.

PMID- 11444662
TI  - Strangulation of pregnant woman leads to one first-degree murder indictment for
      the death of the mother: a medicolegal reconsideration of
      maternal/fetal/homicide.
AB  - A Hispanic woman, 7 1/4, to 7 1/2 lunar months pregnant, was strangled to death
      by her common-law husband. After receiving information from an informant, a
      reporter uncovered the remains of the woman and fetus in a grave in a river bank
      near Eloy, Arizona. The remains were submitted by local law enforcement officials
      to the forensic pathologist for medicolegal examination. After this analysis,
      they were turned over to the consulting forensic anthropologist for positive
      identification of the mother and for fetal age determination to assess possible
      viability. During the 1970s and 1980s, viability for a fetus of this age was
      thought possible, although not probable. Prosecution of the common-law husband on
      the charge of first-degree murder of his wife was successful, whereas a
      comparable charge for the fetus was not sought. Many issues are raised, including
      gestational age estimation in relation to fetal viability. Fetal age is
      reassessed by means of measurements from diaphyseal lengths. These measurements
      allowed for comparability of fetal age estimations between published studies,
      with discussion of changing dates of fetal viability made possible through
      technologic advances. Because fetal viability changes with these advances, it is
      necessary to establish and update the guidelines for medicolegal practice.

PMID- 11444663
TI  - Automated fluorescence analysis of CAG repeats at the human androgen receptor
      gene (HUMARA): evaluation of polymorphism in an Italian sample and report of a
      new allele.
AB  - The HUMARA CAG repeats polymorphism was studied in an Italian population sample.
      Polymerase chain reaction amplification and automated fluorescent analysis were
      used. A total of 19 and 15 repeats was observed in female and male subjects,
      respectively, and one new allele was found. The authors conclude that this X
      linked short tandem repeat, typed without ambiguity and with a heterozygosity of
      0.902, is useful in parentage testing of female subjects.

PMID- 11444664
TI  - Death related to coronary artery fistula after rupture of an aneurysm to the
      coronary sinus.
AB  - Large coronary fistulas are considered to cause myocardial ischemia due to
      diversion of the coronary blood flow. In this case the authors report the reverse
      effect--the spontaneous closure of a large fistulation between the left
      circumflex artery and the coronary sinus evoked angina pectoris in a middle aged
      man, who died several years later. Postmortem examination revealed a coronary
      aneurysm that had ruptured and dissected into the coronary sinus and finally
      thrombosed. The origin of the aneurysm could be congenital but perhaps also
      represents a healed stage of Kawasaki disease.

PMID- 11444665
TI  - Palliative pain therapy at the end of life and forensic medicine issues.
AB  - An 83-year-old woman with a history of Alzheimer's disease and breast cancer died
      at home while receiving palliative pain therapy with oral morphine from her
      family for metastatic breast cancer. Allegations of mistreatment were made, and
      this case was ultimately referred to the Office of the Chief Medical Examiner,
      State of Maryland. An autopsy failed to identify any injuries or residual cancer,
      leaving no anatomic explanation for the pain that had been presumed to be
      metastatic breast carcinoma involving bone. The blood free morphine concentration
      was 5,200 ng/ml, and the total morphine concentration was 15,000 ng/ml. This case
      demonstrates the challenges and difficulties in forensic medicine when faced with
      the interpretation of toxicologic results at the end of life.

PMID- 11444666
TI  - Heimlich trauma: a violent maneuver.
AB  - The Heimlich maneuver is a life-saving technique for dislodging foreign material
      from the respiratory tract. This report illustrates intraabdominal injuries,
      including a large mesenteric laceration, mesenteric contusions, and
      intraperitoneal hemorrhage, that occurred in a recipient of a vigorously applied
      Heimlich maneuver. The potential for confusing such injuries with homicidally
      inflicted injuries is emphasized.

PMID- 11444667
TI  - Suicide by hara-kiri: a series of four cases.
AB  - The authors describe four cases of suicide by hara-kiri. This very painful form
      of suicide consists of self-inflicting a wound in the abdomen using a sharp
      instrument. It was first reported in 988 A.D. in the East but has now become rare
      in both the East and West. These four cases occurred over a 40-year period in the
      Trieste and Bari medicolegal area. In two of our cases the victims were afflicted
      with mental illness, whereas the other two suffered from depression. In cases of
      death by hara-kiri, it is important to establish a differential diagnosis between
      suicide and homicide; the presence of trial wounds (inflicted by the victim as a
      form of practice to overcome any hesitation before stabbing the abdomen with the
      cutting weapon) can prove very helpful.

PMID- 11444668
TI  - Evaluation of the addiction history of a dead woman after exhumation and
      sectional hair testing.
AB  - In Greece, sectional hair analysis, in addition to clinical examination, has been
      used as a valuable tool for the confirmation of a person's history of drug use.
      The present report concerns the toxicologic analysis of the exhumed remains and
      hair samples of an 18-year-old woman. Postmortem toxicologic analysis of blood
      and urine confirmed recent opiate and cannabis use and indicated that death was
      associated with heroin abuse. Several months later, the woman's family asked for
      exhumation and reexamination of the body, insisting that the cause of death was
      homicide. The investigating judge ordered exhumation and new medicolegal
      examination of the body. The investigation of the drug profile along the hair
      shaft was undertaken by analyzing hair sections 1 cm from the hair root for
      morphine, 6-monoacetylmorphine, heroin, and cannabinoids. The total lengths of
      the hair samples ranged from 8 to 11 cm. The total morphine levels in the hair
      sections corresponding to the 3-month period before death were significantly
      lower (1.5-2.85 ng/mg) than those of the 4- to 10-month period before death (7.4
      14.8 ng/mg). An interpretation of these results may be occasional drug use (with
      considerable attenuation of use during the last 3 months before death). Decrease
      of tolerance to heroin caused by abstinence and relapse in use could have been
      the cause of death.

PMID- 11444669
TI  - Postmortem measurements of thyroid hormones in blood and vitreous humor combined
      with histology.
AB  - The aim of this study was to investigate whether clinical reference premortem
      values can be used to assess postmortem concentrations of thyroxine,
      triiodothyronine, and thyroid stimulating hormone (TSH), to compare the
      postmortem concentrations in blood and vitreous humor, and to study the
      possibility of diagnosing hyperthyroidism by comparing thyroid histologic
      appearance and postmortem hormone values. Biochemical analyses of free thyroxine
      (FT4), free triiodothyronine (FT3), and TSH in femoral blood and vitreous humor
      were made in 38 cases. In 40 cases, the hormones and thyroid histologic
      appearance were studied; 22 had no significant pathologic changes, and 18 showed
      focal hyperplasia of the follicular epithelium. A positive correlation was seen
      between the femoral blood and vitreous humor concentrations of FT4 (R = 0.66) but
      not between the corresponding concentrations of FT3 and TSH. A positive
      correlation was also seen between FT3 and FT4 in femoral blood (R = 0.74). In
      cases with normal thyroid histologic appearance, 58% were found to have FT4
      values >24 pmol/L (clinical reference interval 9-24 pmol/L), mean value 27.5 +/-
      9.4 pmol/L), which did not differ from the FT4 values in the cases with
      hyperplasia, 31.6 +/- 15 pmol/L. Only 5% of the T3 measurements in the group with
      normal histologic appearance were >9 pmol/L (clinical reference interval 3-9
      pmol/L). The mean value of FT3 in cases with normal histologic appearance was 3.4
      +/- 1.3 pmol/L, and in the group with hyperplasia 8.6 +/- 6.1 pmol/L. The
      difference was statistically significant P < .005). It is concluded that
      postmortem values of FT3 and FT4 in femoral blood are fairly comparable to
      premortem clinical reference values, but the upper normal limit, especially for
      T4, has to be adjusted upward. Analysis of vitreous humor cannot be used post
      mortem to assess thyroid function. Histologically, hyperplastic changes correlate
      well with elevated FT3 in femoral blood.

PMID- 11444670
TI  - Sudden death from hyponatremia and hypokalemia in a woman with Gardner syndrome.
AB  - The authors present the case of a 39-year-old woman with Gardner syndrome who
      died from marked hyponatremia and hypokalemia. Gardner syndrome is a rare variant
      of the familial adenomatous polyposis syndrome in which the affected individual
      develops thousands of polyps within the gastrointestinal tract, with a 100% risk
      of eventual malignant change. Individuals with Gardner syndrome also develop a
      variety of extra gastrointestinal abnormalities. In the case presented, a woman
      with a clinical history of Gardner syndrome who had previously undergone a total
      colectomy with ileorectal anastomosis presented to the hospital with a recent
      history of sore throat, fever, diarrhea, and abdominal pain. The symptoms were
      considered clinically to be due to a viral gastroenteritis. She was admitted to
      the hospital, where she had episodes of collapse believed to be vasovagal in
      origin. She suffered a cardiorespiratory arrest and died 24 hours after
      admission. After her death, electrolyte estimation performed on blood taken
      shortly before death revealed severe hyponatremia and hypokalemia. Postmortem
      examination showed the gastric mucosa to be virtually covered by innumerable
      adenomatous and hyperplastic polyps. Fewer polyps were seen within the small
      bowel. There was no evidence of malignancy. The features were consistent with
      Gardner syndrome. Hyponatremia and hypokalemia have been described in patients
      with villous adenomas and in familial adenomatous polyposis syndromes associated
      with numerous colonic polyps. The cause of death in this case was considered to
      be hyponatremia and hypokalemia associated with florid gastric polyps in a woman
      with Gardner syndrome. Viral gastroenteritis contributed to the death by causing
      further electrolyte depletion. To the best of the authors' knowledge, death in
      Gardner syndrome has not been described as attributable to such metabolic
      disturbance, in particular in those who have only gastric, small bowel, and
      rectal polyps remaining after total colectomy.

PMID- 11444671
TI  - Hepatic abscess formation and unexpected death: a delayed complication of occult
      intraabdominal foreign body.
AB  - A case of unexpected death in a 65-year-old woman, caused by a migrating foreign
      body that resulted in multifocal hepatic abscesses, is reported. The foreign body
      was subsequently identified as a portion of chicken fibula. The prolonged time
      course of the illness, with relatively nonspecific symptoms and signs, resulted
      in establishment of the diagnosis only at autopsy.

PMID- 11444672
TI  - Traditional punishment and unexpected death in Central Australia.
AB  - Three cases of traditional punishment in Central Australian Aboriginal men are
      presented in which the thighs were speared or stabbed as part of a "payback"
      system. In two cases, an unexpected effect of the stabbing or spearing was death
      due to severing of major leg vessels. The relationship between customary
      Aboriginal law and general law in Australia has not been clearly defined;
      however, these cases demonstrate that significant and untoward effects may result
      from traditional punishments. Pathologists working near traditional Australian
      Aboriginal communities may still encounter such injuries at autopsy.

PMID- 11444673
TI  - Coprophagic cafe coronary.
AB  - A 74-year-old man who had been institutionalized for severe multiinfarct dementia
      was found dead in bed. He had a history of compulsive ingestion of food and other
      materials, including feces. At autopsy, a 65-g bolus of fecal material was
      impacted within the laryngopharynx, occluding the inlet of the larynx. This case
      demonstrates an unusual coprophagic variant of cafe coronary syndrome and
      emphasizes that demented individuals with pica are at risk of sudden death from
      ingestion of a wide variety of materials, including, but not limited to, food.

PMID- 11444674
TI  - Discriminative value of lipids and apolipoproteins in alcoholics.
AB  - 1. It is important to detect alcohol use in its early stages so that
      interventions can be planned effectively. In a bid to screen for alcohol use
      disorders various biochemical assessments have been advocated. 2. It has been
      seen that moderate to heavy alcohol consumption appears to elevate ApoA1 though
      the effect of alcohol consumption on ApoB is not well defined. 3. Present study
      was planned to evaluate the contribution of lipid profile and lipoprotein
      measures for the diagnosis of alcohol use disorder in 75 alcohol dependent and 45
      normal healthy controls. 4. Based on the TC, TG, HDL/LDL-c, HDL-c/TC, ApoA1,
      ApoB, and ApoA1/ApoB a discriminant equation was developed for classification of
      alcohol dependent users (alcoholics) and non-users (non-alcoholics) 5. The
      discriminant equation resulted in 84.7% of subjects being correctly classified.
      (94.7% in non-users and 81.1% in alcohol dependent users as alcoholics).

PMID- 11444675
TI  - An open study of paroxetine in hypochondriasis.
AB  - 1. Despite the high prevalence of hypochondriasis, this disorder is found to be
      the focus of research only minimally. 2. This open study evaluates the efficacy
      and tolerance of paroxetine in 11 patients with DSM-III-R hypochondriasis. 3.
      Using paired samples t-test, a significant reduction on measures of
      hypochondriasis was found after 12 weeks of treatment compared to baseline. Two
      patients dropped out prematurely. At post-test, eight out of nine patients who
      completed the study had improved to a clinically relevant degree. Of these, five
      attained scores in the reach of the normal population. 4. In one patient who
      completed the study and one patient who dropped out, tolerance of paroxetine was
      poor, whereas in remaining patients tolerance was moderate to good. 5. The
      results of this study suggest that patients with hypochondriasis may be
      responsive to paroxetine. A controlled study is recommended.

PMID- 11444676
TI  - Sex-related differences in nortriptyline-induced side-effects among depressed
      patients.
AB  - 1. Men and women may differ in their pharmacokinetic responses to tricyclic
      antidepressants (TCAs), in a number of autonomic indices, and in various
      adrenergic receptor mediated responses. Emerging evidence also suggests that
      women may have a lower rate of serotonin synthesis in brain and a greater
      sensitivity to the depressant effects of tryptophan depletion, relative to men.
      However, sex-related differences in TCA-induced side-effects, including increases
      in heart rate (HR), dry mouth, constipation, and difficulty urinating, has not
      been systematically investigated. 2. The authors examined potential sex-related
      differences in the pattern of side-effects during treatment with nortriptyline
      (NT), a TCA that is still widely used. Seventy-eight healthy outpatients who met
      Research Diagnostic Criteria and DSM-III-R criteria for major depression
      participated in a double-blind, randomized parallel trial of NT versus placebo.
      3. Each subject was acutely challenged with either placebo or 50 mg NT prior to
      and after a 6-week treatment with NT. NT doses were adjusted weekly to maintain
      therapeutic plasma levels. Patients were assessed at multiple time points to
      detect the presence of NT-induced side-effects. 4. The initial, single (50 mg)
      dose of NT significantly increased supine HR. Six-week treatment with NT was
      found to significantly increase supine and sitting HRs, irrespective of sex. In
      rechallenge with the single NT dose, there were no significant effects on HR. 5.
      When sex-related differences were examined, HR increases were greater in men than
      women during weeks 4 through 6 of the NT treatment, although no sex-related
      differences were present in plasma NT levels or metabolites. In addition, there
      was a significant NT to placebo difference in self-rated dry mouth for women
      during all 6-weeks of treatment, whereas men showed a significant NT-placebo
      difference during weeks 3 and 5. 6. The results suggest the presence of sex
      related differences in elevated supine HR response during the course of 6-week NT
      treatment. Depressed men may be more susceptible to NT-induced increases in
      supine HR than women.

PMID- 11444677
TI  - A single blind comparison of amisulpride, fluoxetine and clomipramine in the
      treatment of restricting anorectics.
AB  - 1. The study evaluated the efficacy of amisulpride, fluoxetine and clomipramine
      at the beginning of the re-feeding phase of the treatment of restricting anorexia
      nervosa according to DSM-IV criteria. 2. 13 patients, mean weight 37.61 kg +/-
      9.80 SD, were treated with clomipramine at a mean dosage of 57.69 mg +/- 25.79
      SD; 10 patients, mean weight 40.90 kg +/- 6.98 SD, were treated with fluoxetine
      at a mean dosage of 28.00 mg +/- 10.32 SD; 12 patients, mean weight 38.41 kg +/-
      8.33 SD, were treated with amisulpride at a mean dosage of 50.00 mg +/- 0.00 SD.
      3. Clinical evaluation was carried out under single-blind condition at basal time
      and after three months by a structured clinical interview, the Eating Disorder
      Interview based on Long Interval Follow-up Evaluation (LIFE II BEI). 4. Patients
      treated with amisulpride showed a more significant increase (p=0.016) of mean
      weight. Concerning weight phobia, body image disturbance and amenorrhoea, no
      significant difference resulted.

PMID- 11444678
TI  - Activation of noradrenergic mechanism attenuates glutamate-induced vasopressor
      responses in the pons and medulla of cats in vivo.
AB  - 1. Using anesthetized cats, the authors examined the noradrenergic modulation of
      the glutamate induced pressor and depressor responses in various brainstem areas,
      including pontine gigantocellular tegmental field (FTG), dorsomedial medulla
      (DM), rostral ventrolateral medulla (RVLM), and caudal ventrolateral medulla
      (CVLM). 2. Unilateral microinjection of L-glutamate (Glu, 3 nmol in 30 nL saline)
      into FTG, DM and RVLM produced an increase in systemic arterial pressure (SAP)
      and a decrease in heart rate (HR), while into CVLM produced decreases of SAP and
      HR. 3. Application of norepinephrine (NE) into the pressor areas (0.05 to 5 nmol)
      did not alter the resting SAP and HR, but significantly attenuated the Glu
      induced pressor response with an order of potency: FTG > DM > RVLM. In the
      depressor CVLM, NE alone produced a dose-dependent decrease of resting SAP and
      HR, but did not affect the Glu-induced depressor responses. 4. The involvement of
      different adrenoceptor subtypes was further investigated by application of
      selective adrenoceptor agonists including phenylephrine (alpha1), clonidine
      (alpha2), and isoproterenol (beta). Responses to these agonists are similar to
      those elicited by NE, except that only alpha-adrenoceptor agonists could
      antagonize the Glu-induced pressor responses of the RVLM. 5. Our observations
      indicate that NE not only inhibits the pressor mechanisms in various brainstem
      areas but also elicits a direct depressor response in CVLM. These findings also
      suggest that NE acts more likely a neurotransmitter, rather than a modulator, in
      the CVLM.

PMID- 11444679
TI  - Behavioral screening of two mouse lines selected for different brain weight.
AB  - 1. Several behavioral tests were used to compare two lines of mice selected for
      large (LB) and small brain (SB) weight on the basis of brain/body weight ratio
      values. 2. An elevated pain sensitivity as well more intense startle response was
      shown in SB mice in comparison with LB mice. 3. In inescapable situations of slip
      funnel and tail suspension tests, analogues of the Porsolt swim test, higher
      immobility scores in SB mice suggest an increased level of fear and/or anxiety
      the stress situations. 4. The SB mice demonstrated higher levels of locomotion in
      open field and cross-maze tests. In the latter test, the SB mice also showed
      increased tendency for stereotyped alternation of two arms during maze
      exploration. 5. Acute administration of a moderate dose of ethanol (3 g/kg) had
      opposite effects on the total time of cross-maze exploration: this measure
      increased in the SB and decreased in the LB line. By contrast, the tendency for
      stereotypy was similarly increased and the efficacy of maze exploration decreased
      in both lines.

PMID- 11444680
TI  - Isolation rearing induced fear-like behavior without affecting learning abilities
      of Wistar rats.
AB  - 1. Isolation-reared rats display fear-like behavior and depressive-like behavior
      in several behavioral tasks, suggesting that isolation rearing may model certain
      aspects of human psychopathologies. 2. After weaning (20 days old), male and
      female Wistar rats were isolation-reared during 20, 50 or 70 days. After that,
      they were tested in the elevated plus maze test, and in the open field test.
      Another group of isolation-reared rats (70 days of isolation) were tested in an
      auto-shaping task. 3. Isolation-reared rats displayed high levels of fear-like
      behavior in the elevated plus-maze test, and hyperlocomotion in the open field
      test. But, isolation-reared rats learned an auto-shaping task. 4. In conclusion,
      isolation rearing induced fear-like behavior, without affect learning abilities
      of rats.

PMID- 11444681
TI  - Behavioral and neurochemical effects of anpirtoline and citalopram in isolated
      and group housed mice.
AB  - Acute effects of serotonergic drugs acting via different mechanisms were
      investigated by a social interaction test and subsequent determination of
      serotonin and dopamine metabolisms in mice housed in groups or isolated for 6
      weeks. A resident/intruder test was performed with anpirtoline (5-HT1B receptor
      agonist in rodents; 1 mg/kg), citalopram (SSRI; 0.5 mg/kg) and saline treatment
      before animals were decapitated and different brain regions were frozen for
      subsequent HPLC-analyses. Behavioral investigations indicated a strong increase
      of aggressive behavior after 6 weeks of isolation housing. Acute citalopram
      treatment did not influence behavioral parameters of isolated and group housed
      mice. In contrast, anpirtoline antagonized isolation induced aggressive
      behavioral components in a specific manner. Analysis of dopamine and serotonin
      metabolism revealed that citalopram treatment did not affect dopamine metabolism,
      but reduced serotonin metabolism in the striatum, hippocampus, cortex and
      midbrain independent of housing conditions. In contrast, anpirtoline treatment
      increased dopamine metabolism in cortex, striatum and midbrain as well as
      influenced serotonin metabolism in a structure- and state-specific manner.
      Whereas anpirtoline decreased serotonin metabolism in the cortex, the midbrain
      and the hippocampus independent of housing conditions, in the striatum
      anpirtoline abolished the isolation induced decrease of serotonin metabolism.
      These results indicate that anpirtoline might induce antiaggressive effects via
      postsynaptic receptor- and structure-specific activation of serotonergic but also
      dopaminergic processes, whereas structure independent increase of synaptic
      serotonin via citalopram was ineffective to reverse aggressivity in isolated
      mice.

PMID- 11444682
TI  - Behavioral analysis indicates benzodiazepine-tolerance mediated by the
      benzodiazepine binding-site at the GABA(A)-receptor.
AB  - 1. GABA(A)-receptor induced changes in locomotion and anxiety-like behaviors were
      studied in rats using an open-field and an elevated plus-maze. Acute and chronic
      doses of the benzodiazepine diazepam without and in combination with the GABA
      uptake inhibitor SKF-89976A were investigated. 2. Fifty-six male rats of the
      strain PVG/OlaHsd (PVG; 180-200 g body wt) were used to assess the influence of
      the benzodiazepine binding-site to the development of tolerance. Rats were
      divided into six groups: The first receiving saline (0.9%), the second and third
      diazepam (10.0 mg/kg) daily for 23 days with or without an acute challenge of 2.0
      mg/kg diazepam. The fourth group received diazepam (10.0 mg/kg) daily and acutely
      SKF-89976A (15.0 mg/kg) plus diazepam and the fifth and sixth group received
      acute treatment with diazepam (2.0 mg/kg) or SKF-89976A (15.0 mg/kg). 3. Under
      chronic treatment with diazepam the animals became tolerant to acute doses of
      diazepam in activity and anxiety-related behaviors. Acute treatment with SKF
      89976A increased exploration. Parameters expressing anxiolytic-like behaviors
      were increased, too, but not all of them significantly. In diazepam tolerant
      animals SKF-89976A produced anxiolytic-like behaviors 4. We conclude that the BZ-
      and not the GABA-binding site at the GABA(A)-receptor is involved in the
      development of BZ-tolerance.

PMID- 11444683
TI  - Inactivation of the interpositus nucleus blocks the conditioned response acquired
      by a somatosensory conditioned stimulus in rabbit eyeblink conditioning.
AB  - 1. Earlier studies suggest that the memory trace for the conditioned eyeblink
      reflex is formed and maintained in the interpositus nucleus (IPN) in the deep
      cerebellar nuclei when either an auditory or visual stimulus is used as a
      conditioned stimulus (CS). 2. In the present study, the eyeblink reflex of the
      rabbit was conditioned to a somatosensory CS (an airpuff onto the back). 3. In
      well-trained animals, the IPN was reversibly inactivated by local cooling and the
      existence of the learned responses to the CS was then tested. 4. The reversible
      IPN inactivation blocked the memory trace the somatosensory CS. The finding
      further supports the view that IPN-mediated memory trace formation is not
      dependent on the modality of the CS.

PMID- 11444684
TI  - Serotonergic polymorphisms in patients suffering from alcoholism, anxiety
      disorders and narcolepsy.
AB  - 1. Alterations in the serotonergic neurotransmission have been frequently
      described for patients suffering from alcoholism, anxiety disorders and
      narcolepsy. 2. The authors tested for association of the 5-HT2A receptor
      polymorphism (T102C) and the intron 7 tryptophan hydroxylase (TPH) polymorphism
      (A218C) among 176 alcohol dependent patients, 35 patients with panic disorder, 50
      patients with generalized anxiety disorder, 55 patients with narcolepsy and 87
      healthy controls. 3. Allele and genotype frequencies of the 5-HT2A receptor
      polymorphism (T102C), the intron 7 TPH polymorphism (A218C) were almost similar
      between the patients suffering from alcohol dependence, panic disorder,
      generalized anxiety disorder and narcolepsy. 4. There was no association between
      the 5-HT2A receptor polymorphism (T102C), the intron 7 TPH (A218C) polymorphisms
      and alcohol dependence, panic disorder, generalized anxiety disorder and
      narcolepsy in our subsets of German patients.

PMID- 11444685
TI  - Platelet serotonin concentrations in medicated schizophrenic patients.
AB  - 1. The present study was conducted to investigate the effects of neuroleptic
      administration on platelet serotonin (5-HT) levels, and the relationships between
      platelet 5-HT levels, extrapyramidal symptoms (EPS) and psychopathology in
      schizophrenia. 2. The subjects were 49 regularly medicated inpatients who were
      diagnosed according to the DSM-IV criteria for schizophrenia. Each patient gave
      informed consent for the research involved in this study. All patients were first
      considered as one group and then divided into two groups: those with lower levels
      (LL) and those with higher levels (HL), according to their platelet 5-HT levels.
      Psychotic symptoms and EPS were assessed using the Brief Psychiatric Rating Scale
      and the Drug Induced Extra-Pyramidal Symptoms Scale, respectively. 3. (1) The
      mean level of the platelet 5-HT in the schizophrenics with neuroleptic-treatment
      was significantly lower than that in the normal subjects. (2) The mean level of
      the blood monoamine oxidase (MAO) in the schizophrenics tended to be lower than
      that in the normal subjects. (3) There was no significant difference in the mean
      scores of the positive symptoms, negative symptoms, or EPS between the LL and HL
      groups. (4) Platelet 5-HT levels were not correlated with blood MAO
      concentrations. 4. Overall, these results seem to indicate that (i)
      administration of neuroleptics lowers platelet 5-HT levels, and (ii) platelet 5
      HT levels in the schizophrenics with neuroleptic-treatment do not reflect
      psychopathology of schizophrenia or severity of neuroleptic-induced EPS.

PMID- 11444686
TI  - Similarities in the pattern of regional brain dysfunction in negative
      schizophrenia and unipolar depression: a single photon emission-computed
      tomography and auditory evoked potentials study.
AB  - 1. Negative schizophrenic and unipolar depressive patients were clinically
      assessed. In addition to this SANS and HRSD tests were administered. 2. SPECT and
      AEP measurements were provided. SPECT resulted in quantified brain blood
      perfusion, by means of average "count/pixel" values in the brain regions of
      interest. AEPs resulted in stored multichannel signal waveforms. 3. Statistical
      analyses of blood perfusion measurement data revealed an overall similarity
      between these two disorders in the majority of brain regions. An exception to
      this are the regions: inferior temporalis, inferior occipitalis, hippocampus and
      the anterior basal ganglia. Both diagnostic groups manifested hypofrontality. In
      general, hypoperfusion of the left hemisphere was found, albeit displaying
      different patterns in the two groups investigated. 4. AEP latencies were
      prolonged and found to be similar in both diagnostic groups, whilst AEP
      amplitudes were smaller in schizophrenics compared to depressives.

PMID- 11444687
TI  - Tracing the wild genetic stocks of crop plants.

PMID- 11444688
TI  - Imprinting and deviation from Mendelian transmission ratios.
AB  - Deviations from a Mendelian 1:1 transmission ratio have been observed in human
      and mouse chromosomes. With few exceptions, the underlying mechanism of the
      transmission-ratio distortion remains obscure. We tested a hypothesis that
      grandparental-origin dependent transmission-ratio distortion is related to
      imprinting and possibly results from the loss of embryos which carry imprinted
      genes with imprinting marks that have been incorrectly reset. We analyzed
      transmission of alleles in four regions of the human genome that carry imprinted
      genes presumably critical for normal embryonic growth and development: 11p15.5
      (H19, IGF2, HASH2, etc.), 11p13 (WT1), 7p11-12 (GRB10), and 6q25-q27 (IGF2R),
      among the offspring of 31 three-generation Centre d'Etude de polymorphism Humain
      (CEPH) families. Deviations from expected 1:1 ratios were found in the maternal
      chromosomes for regions 11p15.5, 11p13, and 6q25-27 and in the paternal
      chromosomes for regions 11p15 and 7p11-p12. The likelihood of the results was
      assessed empirically to be statistically significant (p = 0.0008), suggesting
      that the transmission ratios in the imprinted regions significantly deviated from
      1:1. We did not find deviations from a 1:1 transmission ratio in imprinted
      regions that are not crucial for embryo viability (13q14 and 15q11-q13). The
      analysis of a larger set of 51 families for the 11p15.5 region suggests that
      there is heterogeneity among the families with regard to the transmission of
      11p15.5 alleles. The results of this study are consistent with the hypothesis
      that grandparental-origin dependent transmission-ratio distortion is related to
      imprinting and embryo loss.

PMID- 11444689
TI  - Polyploid formation in cotton is not accompanied by rapid genomic changes.
AB  - Recent work has demonstrated that allopolyploid speciation in plants may be
      associated with non-Mendelian genomic changes in the early generations following
      polyploid synthesis. To address the question of whether rapid genomic changes
      also occur in allopolyploid cotton (Gossypium) species, amplified fragment length
      polymorphism (AFLP) analysis was performed to evaluate nine sets of newly
      synthesized allotetraploid and allohexaploid plants, their parents, and the
      selfed progeny from colchicine-doubled synthetics. Using both methylation
      sensitive and methylation-insensitive enzymes, the extent of fragment additivity
      in newly combined genomes was ascertained for a total of approximately 22,000
      genomic loci. Fragment additivity was observed in nearly all cases, with the few
      exceptions most likely reflecting parental heterozygosity or experimental error.
      In addition, genomic Southern analysis on six sets of synthetic allopolyploids
      probed with five retrotransposons also revealed complete additivity. Because no
      alterations were observed using methylation-sensitive isoschizomers, epigenetic
      changes following polyploid synthesis were also minimal. These indications of
      genomic additivity and epigenetic stasis during allopolyploid formation provide a
      contrast to recent evidence from several model plant allopolyploids, most notably
      wheat and Brassica, where rapid and unexplained genomic changes have been
      reported. In addition, the data contrast with evidence from repetitive DNAs in
      Gossypium, some of which are subject to non-Mendelian molecular evolutionary
      phenomena in extant polyploids. These contrasts indicate polyploid speciation in
      plants is accompanied by a diverse array of molecular evolutionary phenomena,
      which will vary among both genomic constituents and taxa.

PMID- 11444690
TI  - 5S ribosomal and U1 small nuclear RNA genes: a new linkage type in the genome of
      a crustacean that has three different tandemly repeated units containing 5S
      ribosomal DNA sequences.
AB  - We investigated the 5S ribosomal RNA (rRNA) genes of the isopod crustacean
      Asellus aquaticus. Using PCR amplification, three different tandemly repeated
      units containing 5S rDNA were identified. Two of the three sequences were cloned
      and sequenced. One of them was 1842 bp and presented a 5S rRNA gene and a U1
      small nuclear RNA (snRNA) gene. This type of linkage had never been observed
      before. The other repeat consisted of 477 bp and contained only an incomplete 5S
      rRNA gene lacking the first eight nucleotides and a spacer sequence. The third
      sequence was 6553 bp long and contained a 5S rRNA gene and the four core histone
      genes. The PCR products were used as probes in fluorescent in situ hybridization
      (FISH) experiments to locate them on chromosomes of A. aquaticus. The possible
      evolutionary origin of the three repeated units is discussed.

PMID- 11444691
TI  - Diversity and genetic structure in populations of Pseudotsuga menziesii
      (Pinaceae) at chloroplast microsatellite loci.
AB  - Genetic variation was compared between uniparentally-inherited (chloroplast
      simple sequence repeats, cpSSRs) vs. biparentally-inherited (isozyme and random
      amplified polymorphic DNA, RAPD) genetic markers in Douglas-fir (Pseudotsuga
      mensiezii) from British Columbia. Three-hundred twenty-three individuals from 11
      populations were assayed. In Douglas-fir, the cpSSR primer sites were well
      conserved relative to Pinus thunbergii (11 of 17 loci clearly amplified), but
      only 3 loci were appreciably polymorphic. At these cpSSR loci, we found an
      unexpectedly low level of polymorphism within populations, and no genetic
      differentiation among populations. By contrast, the nuclear markers showed
      variation typical of conifers, with significant among-population differentiation.
      This difference is likely the outcome of both historical factors and high pollen
      dispersal.

PMID- 11444692
TI  - Isolation of a chromosomally engineered durum wheat line carrying the Aegilops
      ventricosa pchl gene for resistance to eyespot.
AB  - The chromosome 7Dv of Aegilops ventricosa (syn. Triticum ventricosum, 2n = 4x =
      28, genome DvDvMvMv) carries the gene Pch1 for resistance to eyespot. This gene
      has previously been transferred to chromosome 7D of bread wheat, T. aestivum (2n
      = 6x = 42, genome AABBDD). To (1) enhance the level of resistance of bread wheat
      by increasing the copy number of Pch1, and (2) create eyespot-resistant
      triticales, meiotically stable Pch1-carrying durum lines were selected from the
      backcross progenies of a cross between Ae. ventricosa and T. durum cv. Creso ph1c
      (2n = 4x = 28, genome AABB). The Pch1 transfer, likely resulting from
      homoeologous recombination, was located at the distal position on the long arm of
      chromosome 7A. The 7A microsatellite marker Xgwm 698 was found closely linked in
      repulsion to the introgression in the resistant recombination lines, and the
      endopeptidase allele located on chromosome 7A of cv. Creso ph1c was lost.

PMID- 11444693
TI  - Relationship of hepatocyte ploidy levels with body size and growth rate in
      mammals.
AB  - To elucidate possible causes of the elevation of genome number in somatic cells,
      hepatocyte ploidy levels were measured cytofluorimetrically and related to the
      organismal parameters (body size, postnatal growth rate, and postnatal
      development type) in 53 mammalian species. Metabolic scope (ratio of maximal
      metabolic rate to basal metabolic rate) was also included in 23 species. Body
      masses ranged 10(5) times, and growth rate more than 30 times. Postnatal growth
      rate was found to have the strongest effect on the hepatocyte ploidy. At a fixed
      body mass the growth rate closely correlates (partial correlation analysis) with
      the cell ploidy level (r = 0.85, P < 10(-6)), whereas at a fixed growth rate body
      mass correlates poorly with ploidy level (r = -0.38, P < 0.01). The mature young
      (precocial mammals) of the species have, on average, a higher cell ploidy level
      than the immature-born (altricial) animals. However, the relationship between
      precocity of young and cell ploidy levels disappears when the influences of
      growth rate and body mass are removed. Interspecies variability of the hepatocyte
      ploidy levels may be explained by different levels of competition between the
      processes of proliferation and differentiation in cells. In turn, the animal
      differences in the levels of this competition are due to differences in growth
      rate. A high negative correlation between the hepatocyte ploidy level and the
      metabolic scope indicates a low safety margin of organs with a high number of
      polyploid cells. This fact allows us to challenge a common opinion that
      increasing ploidy enhances the functional capability of cells or is necessary for
      cell differentiation. Somatic polyploidy can be considered a "cheap" solution of
      growth problems that appear when an organ is working at the limit of its
      capabilities.

PMID- 11444694
TI  - New evidence for the synteny of rice chromosome 1 and barley chromosome 3H from
      rice expressed sequence tags.
AB  - To provide improved access to the wealth of resources and genomic information
      that is presently being developed for rice a set of 88 rice expressed sequence
      tags (ESTs) previously mapped on rice chromosome I in the cross 'Nipponbare' x
      'Kasalath' was used for comparative mapping in a cross of the barley cultivars
      'Igri' and 'Franka'. As expected. most (89%) of the clones gave distinct banding
      patterns in barley of which about one-third was polymorphic between 'Igri' and
      'Franka'. These polymorphisms were mapped, and most of these (56%) confirmed that
      rice chromosome 1 and barley chromosome 3H are syntenous. All single-copy markers
      identified conserved collinear positions, while markers with multiple copies did
      so in a few cases only. The markers that were not fitting in the collinear order
      were distributed randomly across the barley genome. The comparative maps of
      barley chromosome 3H and rice chromosome 1 comprise in total 26 common markers
      covering more than 95% of the genetic length of both chromosomes. A 30-fold
      reduction of recombination is seen around the barley centromere, and synteny may
      be interrupted in this region. However, the good overall synteny on a mesoscale
      (1-10 cM) justifies the use of rice as a platform for map-based cloning in
      barley.

PMID- 11444695
TI  - Isolation and characterization of a gene encoding a drought-induced cysteine
      protease in tomato (Lycopersicon esculentum).
AB  - In a previous study, a 65 kDa protein, TDI-65, was found to be accumulated in the
      leaves of drought-stressed tomato (Lycopersicon esculentum cv. Starfire) plants.
      The protein level returns to control level when the drought-stressed plants are
      rewatered. Antibodies raised against the purified protein were used to elucidate
      the subcellular localization of the protein. The protein was found to be mainly
      localized in the nuclei and chloroplasts of drought-stressed leaf cells. To
      identify the nature of the protein, a cDNA library was constructed and screened
      by the purified anti-TDI-65 antibody. A cDNA clone designated tdi-65 was isolated
      and characterized. The deduced amino acid sequences of tdi-65 protein has
      extensive homology with known cysteine proteases such as actinidin and papain.
      Northern blot analysis revealed that tdi-65 mRNA is 10-fold higher in drought
      stressed plants as compared to control and rewatered plants. Similar results were
      observed in the tomato cultivar Ailsa and its near isogenic abscisic acid (ABA)
      deficient mutant line, flacca, suggesting that the gene does not require ABA for
      its expression under drought conditions. Based on the previous immunolocalization
      findings we suggest that tdi-65 encoded cysteine protease functions in relation
      to drought-induced senescence and programmed cell death.

PMID- 11444696
TI  - Resistance gene analogs in barley and their relationship to rust resistance
      genes.
AB  - Regions of amino acid conservation in the NBS domain of NBS-LRR resistance
      proteins facilitated the PCR isolation of eight resistance gene analog (RGA)
      sequences from genomic DNA of rice, barley, and Aegilops tauschii. These clones
      and other RGAs previously isolated from maize, rice, and wheat were assigned to
      13 classes by DNA-sequence comparison and by their patterns of hybridisation to
      restricted barley DNA. Using a doubled-haploid mapping population, probes from 12
      RGA classes were used to map 17 loci in the barley genome. Many of these probes
      have been used for mapping in wheat, and the collective data indicate that the
      positions of orthologous RGAs are conserved between barley and wheat. RGA loci
      were identified in the vicinity of barley leaf rust resistance loci Rph4, Rph7,
      and Rph10. Recombinants were identified between RGA loci and Rph7 and Rph10,
      while a cluster of RGA sequences detected by probe 5.2 cosegregated with Rph4 in
      55 F2 lines.

PMID- 11444697
TI  - Construction of a 1.2-Mb contig including the citrus tristeza virus resistance
      gene locus using a bacterial artificial chromosome library of Poncirus trifoliata
      (L.) Raf.
AB  - The citrus tristeza virus resistance gene (Ctv) is a single dominant gene in
      Poncirus trifoliata, a sexually compatible relative of citrus. To clone this
      gene, a bacterial artificial chromosome (BAC) library has been constructed from
      an individual plant that was homozygous for Ctv. This library contains 45,696
      clones with an average insert size of 80 kb, corresponding to 9.6 genome
      equivalents. Screening of the BAC library with five chloroplast DNA probes
      indicated that 0.58% of the BAC clones contained chloroplast-derived inserts. The
      chromosome walk across the Ctv locus was initiated using three closely linked
      genetic markers: C19, AD8, and Z16. The walk has been completed and a contig of
      ca. 1.2 Mb was constructed. Based on new data, the genetic map in the Ctv region
      was revised, with Ctv being located between AD8-Z16 and C19 at distances of 1.2
      and 0.6 cM, respectively. Utilizing DNA fragments isolated from the contig as
      RFLP markers, the Ctv locus was further mapped to a region of ca. 300 kb. This
      contig contains several putative disease-resistance genes similar to the rice
      Xa21 gene, the tomato Cf-2 gene, and the Arabidopsis thaliana RPS2 gene. This
      library will therefore allow cloning of Ctv and other putative disease-resistance
      genes.

PMID- 11444698
TI  - Molecular characterization and expression analysis of a highly conserved rice
      mago nashil homolog.
AB  - Mago Nashi, a protein initially shown to be essential in the development of the
      Drosophila oocyte, is highly conserved among species and shows no homology to any
      other known cellular proteins. Here we report the nucleotide sequence of a cDNA
      and a partial gene that encode rice Mago Nashi protein homologs. In addition, we
      present the tissue-specific expression pattern of mago nashi at the level of RNA
      and protein. The rice Mago Nashi protein shares at least 73% amino acid identity
      with all known animal homologs. Genomic DNA gel blot analysis indicates that two
      copies of the mago nashi gene exist in the rice genome, one of which has
      identical intron positions to those found in an Arabidopsis homolog. mago nashi
      is expressed in root, leaf and developing seed tissue as determined by RNA and
      protein gel blot analysis. Evidence from Drosophila, Caenorhabditis elegans and
      human studies of Mago Nashi suggests that a major function of this protein is its
      involvement in RNA localization. The highly conserved amino acid sequence of all
      Mago Nashi protein homologs across kingdoms suggests that the plant version of
      this protein may similarly be involved in RNA localization.

PMID- 11444699
TI  - Physical mapping of restriction fragment length polymorphism (RFLP) markers in
      homoeologous groups 1 and 3 chromosomes of wheat by in situ hybridization.
AB  - Using wheat ditelosomic lines and in situ hybridization of biotin-labelled DNA
      probes, 18 restriction fragment length polymorphism (RFLP) markers were
      physically located on homoeologous groups 1 and 3 chromosomes of wheat. Most of
      the markers hybridized to chromosome arms in a physical order concordant with the
      genetic maps. A majority of the markers studied were clustered in non-C-banded,
      distal euchromatic areas, indicating the presence of recombination hot spots and
      cold spots in those regions. However, on IBS the markers were well dispersed,
      which could be due to the abundance of heterochromatin throughout the arm. An
      inversion between Xpsr653 and Xpsr953 was observed on 1AL. One new Xpsr688 locus,
      approximately 20-26% from the centromere, was found on 1AS and 1BS. The physical
      location of Xpsr170 on group 3 chromosomes probably represents an alternative to
      the loci on the genetic map. Finally, Xpsr313 was mapped to two physical loci on
      IDL. Five markers were located to bins consistent with the deletion-based
      physical maps.

PMID- 11444700
TI  - Development, characterisation, and across-taxa utility of oil palm (Elaeis
      guineensis Jacq.) microsatellite markers.
AB  - The results of the development of oil palm (Elaeis guineensis Jacq.)
      microsatellite markers are given step by step, from the screening of libraries
      enriched in (GA)n, (GT)n, and (CCG)n simple-sequence repeats (SSRs) to the final
      characterisation of 21 SSR loci. Also published are primer sequences, estimates
      of allele size range, and expected heterozygosity in E. guineensis and in the
      closely related species E. oleifera, in which an optimal utility of the SSR
      markers was observed. Multivariate data analyses showed the ability of SSR
      markers to efficiently reveal the genetic-diversity structure of the genus Elaeis
      in accordance with known geographical origins and with measured genetic
      relationships based on previous molecular studies. High levels of allelic
      variability indicated that E. guineensis SSRs will be a powerful tool for genetic
      studies of the genus Elaeis, including variety identification and intra- or inter
      specific genetic mapping. PCR amplification tests on a subset of 16 other palm
      species and allele-sequence data showed that E. guineensis SSRs are putative
      transferable markers across palm taxa. In addition, phenetic information based on
      SSR flanking region sequences makes E. guineensis SSR markers a potentially
      useful molecular resource for any researcher studying the phylogeny of palm taxa.

PMID- 11444701
TI  - Mitotic-cycle time and the development of embryo and endosperm in compatible and
      incompatible crosses in tuber-bearing Solanum species.
AB  - To understand the relationship between early seed development and the EBN
      (endosperm balance number) hypothesis, the embryo and endosperm growth rates in
      crosses among Solanum spp. with the same and different EBNs were analyzed. For
      the embryo, the differences in the mean cell-doubling time (MCDT) between the
      compatible species 2x Solanum gourlayi and Solanum acaule was 3.9 h, whereas the
      incompatible species Solanum commersonii had MCDT differences of 10 and 13.9 h
      with 2x S. gourlayi and S. acaule, respectively. The embryo growth rates of the
      2EBN species S. acaule and S. gourlayi were almost twice as fast as that of the
      1EBN species S. commersonii. Nuclei of variable sizes were observed in the
      endosperms resulting from incompatible crosses. The author discusses the
      possibility that the collapse of the endosperm in inter-EBN crosses could be
      caused by differences in the MCDT between the parents that produce hybrid
      endosperms with high levels of DNA synthesis and transcription activity,
      resulting in increased nuclear size. A model is proposed to explain the formation
      of enlarged endosperm nuclei in incompatible crosses in the genus Solanum.

PMID- 11444702
TI  - Simple sequence repeat analysis of a clonally propagated species: a tool for
      managing a grape germplasm collection.
AB  - The USDA germplasm repositories help to preserve the genetic variability of
      important crop species by collecting and maintaining representative cultivars and
      related germplasm. Simple sequence repeat markers with high allelic diversity
      were used to type 41 grapevines from 40 accessions. All vines were either
      seedless table grape cultivars or cultivars with names similar to table grape
      cultivars. The proportion of shared alleles was selected as the most appropriate
      statistical measure of genetic distance for this population. In conjunction with
      morphological traits, known synonyms were confirmed and a previously unknown
      synonym was discovered. An alleged synonym in the literature was disproved by the
      DNA data. The data were consistent with known parentage, where such data were
      available. Two mislabeled vines in the USDA collection were identified. UPGMA
      grouped the cultivars loosely into three groups: a group of nine mostly Middle
      Eastern cultivars, a group of 22 accessions mostly from Russia and Afghanistan
      that were morphologically similar to 'Thompson Seedless', and a third very loose
      group of 11 accessions consisting mostly of eastern European wine grape
      cultivars. The limitations and usefulness of this type of analysis are discussed.

PMID- 11444703
TI  - MicroMeasure: a new computer program for the collection and analysis of
      cytogenetic data.
AB  - The ability to identify individual chromosomes in cytological preparations is an
      essential component of many investigations. While several computer software
      applications have been used to facilitate such quantitative karyotype analysis,
      most of these programs are limited by design for specific types of analyses, or
      can be used only with specific hardware configurations. MicroMeasure is a new
      image analysis application that may be used to collect data for a wide variety of
      chromosomal parameters from electronically captured or scanned images. Unlike
      similar applications, MicroMeasure may be individually configured by the end user
      to suit a wide variety of research needs. This program can be used with most
      common personal computers, and requires no unusual or specific hardware.
      MicroMeasure is made available to the research community without cost by the
      Department of Biology at Colorado State University via the World Wide Web at
      http://www.biology.colostate.edu/MicroMeasure.

PMID- 11444704
TI  - Identification and validation of QTLs for salt tolerance during vegetative growth
      in tomato by selective genotyping.
AB  - The purpose of this study was to identify quantitative trait loci (QTLs) for salt
      tolerance (ST) during vegetative growth (VG) in tomato by distributional extreme
      analysis and compare them with the QTLs previously identified for this trait. A
      BC1 population (N = 792) of a cross between a moderately salt-sensitive
      Lycopersicon esculentum Mill. breeding line (NC84173, maternal and recurrent
      parent) and a salt-tolerant L. pimpinellifolium (Jusl.) Mill. accession (LA722)
      was evaluated for ST in solution cultures containing 700 mM NaCl + 70 mM CaCl2
      (electrical conductivity, EC = 64 dS/m and phiw approximately -35.2 bars). Thirty
      seven BC1 plants (4.7% of the total) that exhibited the highest ST were selected
      (referred to as the selected population), grown to maturity in greenhouse pots
      and self-pollinated to produce BC1S1 progeny seeds. The 37 selected BC1S1 progeny
      families were evaluated for ST and their average performance was compared with
      that of the parental BC1 population before selection. A realized heritability of
      0.50 was obtained for ST in this population. The 37 selected BC1 plants were
      subjected to restriction fragment length polymorphism (RFLP) analysis using 115
      markers, and marker allele frequencies were determined. Allele frequencies for
      the same markers were also determined in an unselected BC1 population (N = 119)
      of the same cross. A trait-based marker analysis (TBA), which measures
      differences in marker allele frequencies between selected and unselected
      populations, was used to identify marker-linked QTLs. Five genomic regions were
      detected on chromosomes 1, 3, 5, 6, and 11 bearing significant QTLs for ST.
      Except for the QTL on chromosome 3, all QTLs had positive alleles contributed
      from the salt tolerant parent LA722. Of the five QTLs, three (those on
      chromosomes 1, 3, and 5) were previously identified for this trait in another
      study, and thus were validated here. Only one of the major QTLs that was
      identified in our previous study was not detected here. This high level of
      conformity between the results of the two studies indicates the genuine nature of
      the identified QTLs and their potential usefulness for ST breeding using marker
      assisted selection (MAS). A few BC1S1 families were identified with most or all
      of the QTLs and with a ST comparable to that of LA722. These families should be
      useful for the development of salt tolerant tomato lines via MAS.

PMID- 11444705
TI  - Ancient and recent duplications of the rainbow trout Wilms' tumor gene.
AB  - The Wilms' tumor suppressor (WT1) gene plays an important role in the development
      and functioning of the genitourinary system, and mutations in this gene are
      associated with nephroblastoma formation in humans. Rainbow trout (Oncorhynchus
      mykiss) is one of the rare animal models that readily form nephroblastomas, yet
      trout express three distinct WT1 genes, one of which is duplicated and inherited
      tetrasomically. Sequence analyses suggest an ancient gene duplication in the
      common ancestor of bony fishes resulted in the formation of two WT1 gene
      families, that conserve the splicing variations of tetrapod WT1, and a second
      duplication event occurred in the trout lineage. The WT1 genes of one family map
      to linkage groups 6 and 27 in the trout genome map. Reverse transcribed
      polymerase chain reaction (RT-PCR) expression analysis demonstrated little
      difference in W

PMID- 11444706
TI  - Instability of bacterial artificial chromosome (BAC) clones containing tandemly
      repeated DNA sequences.
AB  - The cloning and propagation of large DNA fragments as bacterial artificial
      chromosomes (BACs) has become a valuable technique in genome research. BAC clones
      are highly stable in the host, Escherichia coli, a major advantage over yeast
      artificial chromosomes (YACs) in which recombination-induced instability is a
      major drawback. Here we report that BAC clones containing tandemly repeated DNA
      elements are not stable and can undergo drastic deletions during routine library
      maintenance and DNA preparation. Instability was observed in three BAC clones
      from sorghum, rice, and potato, each containing distinct tandem repeats. As many
      as 46% and 74% of the single colonies derived from a rice BAC clone containing 5S
      ribosomal RNA genes had insert deletions after 24 and 120 h of growth,
      respectively. We also demonstrated that BAC insert rearrangement can occur in the
      early stage of library construction and duplication. Thus, a minimum growth
      approach may not avoid the instability problem of such clones. The impact of BAC
      instability on genome research is discussed.

PMID- 11444707
TI  - Exploitation of Arabidopsis-tomato synteny to construct a high-resolution map of
      the ovatecontaining region in tomato chromosome 2.
AB  - High-resolution genetic and physical maps were constructed for the region of
      chromosome 2 containing the major fruit-shape locus ovate. A total of 3,000 NIL
      F2 and F3 NILs derived from Lycopersicon esculentum cv. Yellow Pear (TA503) x L.
      pennellii (a wild tomato) were used to position ovate adjacent to the marker
      TG645 and flanked by markers TX700 and BA10R (a 0.03-cM interval). BAC libraries
      and a BIBAC library were screened with the closest marker, TG645. Genetic mapping
      with the ends of isolated BAC clones revealed that two BAC clones (100 and 140
      kb) both contained the ovate locus. Screening of sequences from these BAC clones
      revealed synteny between this segment of tomato chromosome 2 and the chromosome-4
      region of Arabidopsis containing the BAC clone ATAP22. Microsynteny between the
      two genomes was exploited to find additional markers near the ovate locus. The
      placement of ovate on a BAC clone will now allow cloning of this locus and,
      hence, may open the door to understanding the molecular basis of fruit
      development and also facilitate the genetic engineering of fruit-shape
      characteristics. This also represents the first time that microsynteny with
      Arabidopsis has been exploited for positional cloning purposes in a different
      plant family.

PMID- 11444708
TI  - Analysis of random and specific sequences of nuclear and cytoplasmic DNA in
      diploid and tetraploid american wild rice species (Oryza spp.).
AB  - A sample of American wild rice and other accessions of the genus Oryza were
      studied at polymorphic regions of nuclear, mitochondrial, and chloroplastic
      genomes. First, flow cytometry, genome-specific RAPD markers, and chromosome
      counting were utilized to verify the original ploidy and classification of 230
      accessions studied. Based on these methods, 8% of the accessions were considered
      to be misclassified either taxonomically or as a result of contamination. Second,
      a fine resolution analysis was conducted at genomic regions sampled at random by
      RAPD markers and at specific sites of the chloroplast and mitochondrial DNA by
      cleaved amplified polymorphic sequence (CAPS) analysis. Phylogenetic trees
      resulting from phenetic and cladistic analyses of RAPD, cpDNA, and mtDNA
      polymorphisms were obtained. The results indicated that the American diploid
      species O. glumaepatula should be considered an individual species, distinct from
      O. rufipogon, and confirmed that the American tetraploid species (O. alta, O.
      grandiglumis, and O. latifolia) belong to the O. officinalis complex. The data
      indicate that these species should still be treated as a group rather than as
      three distinct species and that their closest relative is a CC-genome species. It
      was estimated that the diploid and tetraploid American species diverged from O.
      sativa - O. nivara (AA genome) and CC- and BBCC-genome species, respectively, 20
      million years ago.

PMID- 11444709
TI  - Species identification in seven small millet species using polymerase chain
      reaction-restriction fragment length polymorphism of trnS-psbC gene region.
AB  - The chloroplast trnS-psbC gene regions from total genomic DNA of 119 accessions
      from seven small millet species were amplified by polymerase chain reaction (PCR)
      and digested with eight restriction enzymes individually as well as in
      combinations of two enzymes to generate restriction fragment length polymorphism
      (PCR-RFLP). PCR-RFLP with individual enzymes revealed polymorphism between only
      some species. However, all the species could be distinguished by using a
      combination of two enzymes, specifically HaeIII and MspI. PCR-RFLP of 11 to 20
      accessions with the same enzyme combination showed no intraspecific variation,
      which established that the differential banding patterns were species specific.
      In contrast, the same enzyme combination was not useful for differentiating
      different species of the genera Cajanus, Rhyncosia, Abies, Rhizophora, Ceriops,
      and Bruguiera, and it also revealed intraspecies variation in three species of
      Abies. The present study indicated that digestion of trnS-psbC with two four-base
      recognizing enzymes reveals more variation than with either enzyme alone and that
      it may be a method of choice for species identification in some genera.

PMID- 11444710
TI  - Management of pain: best of times, worst of times?

PMID- 11444711
TI  - Screening of patients with complex regional pain syndrome for antecedent
      infections.
AB  - OBJECTIVE: This study was designed to investigate whether Complex Regional Pain
      Syndrome type I (CRPS I) could be linked to any previous infection. PATIENTS:
      Fifty-two patients with CRPS I of one extremity were screened for the presence of
      antibodies against mostly neurotropic microorganisms. RESULTS: Of these 52
      patients, none had antibodies against Treponema pallidum, Borrelia burgdorferi,
      or HTLV-1. Only four patients were positive for Campylobacter jejuni. For
      cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and Toxoplasma gondii,
      seroprevalences were similar to control values. The total seroprevalence of
      Parvovirus B 19 in our CRPS population was 77%, which was significantly higher
      than in an independent Dutch population group (59%). Seroprevalence in lower
      extremity CRPS 1 (94%) was significantly higher than in upper extremity CRPS I
      patients (68%). In this study all patients were seropositive for varicella zoster
      virus (VZV) antibodies, but a high prevalence of VZV antibodies is similar to its
      prevalence in a normal population (>90%). CONCLUSIONS: In this study we found a
      significantly higher seroprevalence of Parvovirus B19 in CRPS I and this is most
      striking in lower extremity CRPS I patients. Further serologic research in other
      geographic areas is needed to provide additional information about a potential
      role of Parvovirus B 19 or other microorganisms in the etiopathogenesis of CRPS
      I.

PMID- 11444712
TI  - Eutectic mixture of local anesthetics reduces pain during intravenous catheter
      insertion in the pediatric patient.
AB  - OBJECTIVE: The objective of this study was to explore the relation between the
      application of a mixture of lidocaine/prilocaine cream (eutectic mixture of local
      anesthetics [EMLA]) before intravenous cannula insertion and perceived pain in
      the pediatric patient. DESIGN: Double-blind placebo-controlled trial. SETTING: A
      general inpatient pediatric ward. PATIENTS: We examined 26 male and 31 female
      patients between the ages of 4 and 12 years who required intravenous cannula
      insertion. Intravenous insertion was performed on 57 patients, with 29 patients
      in the placebo group (mean age, 8.1 years) and 28 in the EMLA group (mean age,
      8.0 years). INTERVENTIONS: Application of either EMLA cream or placebo 45 minutes
      before intravenous cannulation. OUTCOME MEASURES: Pain was scored by the patients
      using a 0- to 10-cm visual analogue scale combined with a Faces pain scale as
      well as visual observation by a nurse. Adverse side effects were recorded in a
      separate table. RESULTS: Data collected and the differences between the placebo
      and treated groups were tested using a Mann-Whitney U test. Those children in the
      EMLA group (mean pain score, 1.25) experienced less pain than those in the
      placebo group (mean, 8.39). There was no statistical significance between age,
      sex, and race. CONCLUSIONS: The authors conclude that a topical preparation of
      lidocaine/prilocaine significantly reduces children's pain during intravenous
      cannula insertion when applied to an intact dermal layer of the skin and that
      this effect occurs within 45 minutes.

PMID- 11444713
TI  - An investigation of symptom-specific muscle hyperreactivity in upper extremity
      cumulative trauma disorder.
AB  - OBJECTIVE: The study examined symptom-specific muscle hyperreactivity in patients
      with chronic pain with upper limb cumulative trauma disorder (CTD). DESIGN: Four
      tasks were presented in counterbalanced order and included neutral, general
      stressor, personal stressor, and pain stressor tasks. Ratings of stressfulness
      and recordings of skin conductance level confirmed the effectiveness of the
      experimental manipulations in inducing stress experiences for all subject groups.
      SETTING: The study was conducted in a university research center. PATIENTS:
      Thirty patients with CTD were matched as closely as possible for age and gender
      to control groups of chronic low back pain, arthritis, and pain-free subjects.
      OUTCOME MEASURES: Surface electromyograph recordings were taken from the
      frontalis, forearm flexors, trapezius, and lower back during baseline and tasks.
      RESULTS: The study found no evidence of greater muscle tension increases or
      extended duration of return to baseline for the CTD or low back pain patients at
      any of the muscle sites for any of the tasks in comparison to control groups.
      CONCLUSIONS: The results indicate that symptom-specific psychophysiological
      responses may be limited to certain subgroups rather than being characteristic of
      chronic musculoskeletal pain patients in general.

PMID- 11444714
TI  - Cardiorespiratory fitness, physical activity level, and chronic pain: are men
      more affected than women?
AB  - OBJECTIVE: To evaluate the cardiorespiratory endurance (CRE) and physical
      activity level of patients with chronic pain compared with healthy subjects.
      DESIGN AND SUBJECTS: Cross-sectional study, with a consecutive sample of 55
      patients with chronic pain (20 men, 35 women). Comparison of CRE and physical
      activity indices obtained in patients with data available in the literature for
      age-matched healthy subjects. SETTING: A multidisciplinary pain center in a city
      of more than 1,000,000 inhabitants. OUTCOME MEASURES: A physical working capacity
      index (PWC65%/kg) and physical activity level scores and subscores obtained with
      two questionnaires (the Baecke and the Five-City Project questionnaires).
      RESULTS: The physiological gender difference in CRE indices that characterizes
      healthy subjects was not observed in patients with chronic pain. When compared
      with values previously obtained in controls, male patients presented with a very
      significant 34% reduction in PWC65%/kg. The 17% reduction found in women hardly
      reached significance level. The Baecke total physical activity score was
      significantly higher in female than in male patients, a finding not observed in
      healthy controls. There was no significant difference between male and female
      patients in the Five-City Project total physical activity score expressed in
      kilocalories per day per kilogram (i.e., normalized for body weight), although
      data from the literature show that healthy men present with a significantly
      higher level of physical activity compared with healthy women. CONCLUSIONS: Data
      on CRE and the physical activity level of patients with chronic pain obtained in
      this study show that chronic pain may have a greater impact on male than female
      patients. Sociocultural factors are probably at the origin of this phenomenon.

PMID- 11444715
TI  - Sexual difficulties of chronic pain patients.
AB  - OBJECTIVE: Description of the specific physical and psychological problems
      associated with sexual activity in patients with chronic pain. DESIGN: Self
      completion questionnaire on extent and nature of sexual difficulties related to
      pain; data on psychological and physical function in respondents; personal and
      medical data for respondents and nonrespondents. PATIENTS: Three hundred twenty
      seven patients with chronic pain in inpatient and outpatient pain programs; 237
      (72%) completed the questionnaire. MEASURES: Extent of general and specific
      sexual problems; anxiety and depression (Hospital Anxiety and Depression Scale
      [HAD]); pain self-efficacy; pain-related disability (Sickness Impact Profile);
      drug use. RESULTS: Respondents were younger and had less depressed mood than
      nonrespondents, but there were no other major differences. Seventy-three percent
      of respondents had pain-related difficulty with sexual activity; most had
      several, in various combinations of problems with arousal, position, exacerbating
      pain, low confidence, performance worries, and relationship problems. All except
      position difficulties were associated with less frequent sexual activity. There
      were few differences between men and women, and only weak relations emerged
      between specific problems and mood and disability. CONCLUSIONS: There is a high
      prevalence of sexual difficulties in patients with chronic pain attending
      treatment, nearly double that of a general UK survey. These difficulties are not
      simply related to mood or disability. The range of problems and patients'
      expressed preferences for help suggest that multidisciplinary intervention is
      required.

PMID- 11444716
TI  - Finding pain between minds and bodies.
AB  - Physicians and patients alike find it easy to divide pain into mental pain and
      physical pain. But close examination of this distinction shows that it fails on
      clinical and philosophical grounds. The body is not a passive conduit for
      information about tissue damage. Nociception is modified and analyzed throughout
      the nervous system. The mind is not a central theater where pain is finally
      apprehended. Pain perception cannot be understood as the private observation of a
      pain sensation. Pain must have mental (e.g., aversion) and physical (e.g.,
      location) elements if it is to qualify as pain. We understand our pain as well as
      the pain of others in terms of socially categorized pain behavior. Pain thus
      originates, not in mind or body, but between minds and bodies. The dualism of
      mental and physical pain cannot be overcome if the biological individual is
      considered in isolation. Mental and physical pain can only be reconciled if their
      common interpersonal roots are understood. This interpersonal view of pain can
      help clarify some clinical and moral dilemmas in the care of patients with pain.

PMID- 11444717
TI  - Surgical patients' fear of addiction to pain medication: the effect of an
      educational program for clinicians.
AB  - OBJECTIVE: The appropriate and optimal use of analgesics is essential for the
      adequate management of postoperative pain. Concern that use of opioid analgesics
      contributes to the development of addiction is a barrier to effective pain
      relief. The purpose of this study was to determine the prevalence of fear of
      addiction in postoperative patients in relation to surgical outcomes and staff
      participation in an educational program. DESIGN: Two treatment levels (program
      vs. control) and three data collection periods (before program, immediately after
      the program, and 6 months after the program). SETTING: Six community hospitals
      with 100-500-bed capacities in a southeastern state. PATIENTS: Seven hundred
      eighty-seven patients who had undergone orthopedic or laparotomy procedures.
      INTERVENTIONS: Staff at three of the six hospitals received an educational
      program to promote implementation of Agency for Health Care Policy and Research
      acute pain management guidelines. OUTCOME MEASURES: Patient report of
      preoperative and postoperative fear of addiction, satisfaction with pain
      treatment, communication with clinicians, and pain intensity. RESULTS: Only 10.8%
      of the sample reported preoperative or postoperative fear of addiction. Staff
      participation in the educational program was found to decrease fear of addiction
      in this sample. Fear of addiction was also related to surgery type, with disc
      surgery patients more likely to report fear of addiction as compared with
      patients undergoing other types of surgery. Fear of addiction was not related to
      other outcomes in this sample. CONCLUSIONS: Fear of addiction is not prevalent
      among postoperative patients, yet clinician education can further decrease the
      proportion of surgical patients who fear of addiction to pain medication.

PMID- 11444718
TI  - Pain catastrophizing predicts pain intensity, disability, and psychological
      distress independent of the level of physical impairment.
AB  - OBJECTIVE: The aim of the current study was to examine the relation between
      catastrophizing and pain intensity, pain-related disability, and psychological
      distress in a group of patients with chronic pain, controlling for the level of
      physical impairment. Furthermore, it was examined whether these relations are the
      same for three subgroups of chronic pain patients: those with chronic low back
      pain, those with chronic musculoskeletal pain other than low back pain, and those
      with miscellaneous chronic pain complaints, low back pain and musculoskeletal
      pain excluded. DESIGN: Correlational, cross-sectional. PATIENTS AND SETTING:
      Participants in this study were 211 consecutive referrals presenting to a
      university hospital pain management and research center, all of whom had a
      chronic pain problem. RESULTS: Overall, chronic pain patients who catastrophize
      reported more pain intensity, felt more disabled by their pain problem, and
      experienced more psychological distress. Regression analyses revealed that
      catastrophizing was a potent predictor of pain intensity, disability, and
      psychological distress, even when controlled for physical impairment. No
      fundamental differences between the three subgroups were found in this respect.
      Finally, it was demonstrated that there was no relation between physical
      impairment and catastrophizing. CONCLUSIONS: It was concluded that for different
      subgroups of chronic pain patients, catastrophizing plays a crucial role in the
      chronic pain experience, significantly contributing to the variance of pain
      intensity, pain-related disability, and psychological distress. These relations
      are not confounded by the level of physical impairment. Some clinical
      implications of the results are discussed. Finally, the authors concluded that
      these results support the validity of a cognitive-behavioral conceptualization of
      chronic pain-related disability.

PMID- 11444719
TI  - Pain treatment thresholds in children after major surgery.
AB  - OBJECTIVE: The objectives of this study were to use a self-report pain scale to
      examine child pain treatment thresholds after major surgery (i.e., the level of
      pain they are comfortable with before requiring analgesia), as well as to examine
      agreement between mother-, nurse-, and child-rated pain treatment thresholds.
      METHODS: Twenty-five children aged 6 to 16 years were interviewed for 3
      consecutive days after major surgery. Subjects used the Faces Pain Scale to rate
      their current pain, worst postoperative pain, and pain level at which they would
      like to receive analgesia (the pain treatment threshold). Parents and nurses also
      estimated the child pain treatment thresholds. RESULTS: For day 1, mean pain was
      1.86 of a maximum of 6, mean worst pain was 4.16, and mean pain treatment
      threshold was 2.28. For day 2, these values were 1.90, 4.10, and 2.54, and for
      day 3 they were 1.62, 4.56, and 1.85, respectively. Mean scores for all 3 days
      were as follows: pain, 1.79; worst pain, 4.15; and pain treatment threshold,
      2.33. Although mother-nurse ratings were correlated (0.471), mother-child and
      nurse-child ratings were not significantly correlated. Using the pain treatment
      threshold as the criterion, 36% of our subjects were undermedicated after the
      first day of surgery. CONCLUSION: Pain treatment thresholds seem to be lower in
      children after major as compared with minor surgery. Parents and nurses are not
      accurate in rating child pain treatment thresholds. Parents tended to
      overestimate their child's pain treatment threshold, whereas nurses were less
      consistent in their scoring.

PMID- 11444720
TI  - Facial expression of children receiving immunizations: a principal components
      analysis of the child facial coding system.
AB  - OBJECTIVE: To identify the structure of facial reaction to procedural pain and to
      determine the subset of facial actions that best describe the response. DESIGN:
      Observational. SETTING: Five rural and five urban physicians' offices. PATIENTS:
      One hundred twenty-three children aged 4 to 5 years undergoing routine
      diphtheria, pertussis, tetanus, and polio immunization. OUTCOME MEASURES: The
      Child Facial Coding System, comprising 13 discrete facial actions, was used to
      code each second of five 10-second phases from videotape: baseline, preneedle,
      needle, postneedle, and posthandling. Parents and a technician provided visual
      analog scale ratings of children's pain. Children provided a self-report using a
      Faces Pain Scale, and parents and nurses rated the children's pain and anxiety
      using visual analog scales. RESULTS: A "pain face" similar to that reported in
      adults emerged with the onset of pain. Principal component analyses revealed the
      frequency and intensity of facial action during the needle phase could be
      represented by components reflecting pain sensation, a "brave face," and the
      children's expectations for pain. Children's Faces Pain Scale and adult visual
      analog scale ratings were best predicted by components reflecting pain sensation
      and expectations of high pain. CONCLUSIONS: These results provide a preliminary
      indication that the Child Facial Coding System can be reduced to components that
      reflect several aspects of children's acute pain experience and predict self
      reports and observer reports of children's pain.

PMID- 11444721
TI  - Drug-induced liver disorders: implications for drug development and regulation.
AB  - Drug-induced hepatotoxicity is a frequent cause of liver disease. Although often
      presenting as acute hepatitis and/or cholestasis, virtually any clinical
      pathological pattern of acute or chronic liver disease can occur. Most reactions
      occur in a small proportion of the population using a particular drug. Each drug
      associated with hepatotoxicity tends to have a characteristic signature regarding
      latency and pattern of injury. The mechanism can be drug metabolism-dependent or
      related to the chemical properties of the parent drug. The former are immune
      mediated or due to metabolic idiosyncrasy. Monitoring serum ALT levels is of
      unproven effectiveness but should be considered when there is an increased risk
      of delayed onset serious hepatitis-like reactions. The key for the future is
      improved identification of toxic potential in preclinical studies, clinical
      trials and postmarketing experience. The elucidation of the genetic and
      environmental mechanisms contributing to delayed idiosyncratic reactions is a
      major barrier to overcome in this field.

PMID- 11444722
TI  - Drug-induced thrombotic microangiopathy: incidence, prevention and management.
AB  - The term thrombotic microangiopathy (TMA) describes syndromes characterised by
      microangiopathic haemolytic anaemia, thrombocytopenia and variable signs of organ
      damage due to platelet thrombi in the microcirculation. In children, infections
      with Shigella dysenteriae type 1 or particular strains of Escherichia coli are
      the most common cause of TMA; in adults, a variety of underlying causes have been
      identified, such as bacterial and viral infections, bone marrow and organ
      transplantation, pregnancy, immune disorders and certain drugs. Although drug
      induced TMA is a rare condition, it causes significant morbidity and mortality.
      Antineoplastic therapy may induce TMA. Most of the cases reported are associated
      with mitomycin. TMA has also been associated with cyclosporin, tacrolimus,
      muromonab-CD3 (OKT3) and other drugs such as interferon, anti-aggregating agents
      (ticlopidine, clopidogrel) and quinine. The early diagnosis of drug-induced TMA
      may be vital. Strict monitoring of renal function, urine and blood abnormalities,
      and arterial pressure has to be performed in patients undergoing therapy with
      potentially toxic drugs. The drug must be discontinued immediately in the case of
      suspected TMA. Treatment modalities sometimes effective in other forms of TMA
      have been used empirically. Although plasma exchange therapy seems to be of
      value, the effectiveness of this approach has yet to be proved in multicentre,
      randomised clinical studies.

PMID- 11444723
TI  - Management of paracetamol overdose: current controversies.
AB  - Paracetamol (acetaminophen) is one of the most frequently used analgesics, and is
      the most commonly used substance in self-poisoning in the US and UK. Paracetamol
      toxicity is manifested primarily in the liver. Treatment with N-acetyl-cysteine
      (NAC), if started within 10 hours from ingestion, can prevent hepatic damage in
      most cases. Pharmacokinetic data relating plasma paracetamol concentration to
      time after ingestion have been used to generate a 'probable hepatoxicity line' to
      predict which cases of paracetamol overdose will result in hepatotoxicity and
      should be treated with NAC. However, later studies use a 25% lower line as their
      'possible hepatotoxicity line'. Although adopting the original line may save
      considerable resources, further studies are needed to determine whether such an
      approach is safe. On the basis of the metabolism of paracetamol, several risk
      factors for paracetamol toxicity have been proposed. These risk factors include
      long term alcohol (ethanol) ingestion, fasting and treatment with drugs that
      induce the cytochrome P450 2E1 enzyme system. Although some studies have
      suggested that these risk factors may be associated with worse prognosis, the
      data are inconclusive. However, until further evidence is available, we suggest
      that the lower line should be used when risk factors are present. In Canada and
      the UK, the intravenous regimen for NAC is used almost exclusively; in the US, an
      oral regimen is used. Both regimens have been shown to be effective. There is no
      large scale study with direct comparison between these 2 therapeutic protocols
      and controversy still exists as to which regimen is superior. During the last few
      years there has been an increase in the number of reports of liver failure
      associated with prolonged paracetamol administration for therapeutic reasons. The
      true incidence of this phenomenon is not known. We suggest testing liver enzyme
      levels if a child has received more than 75 mg/kg/day of paracetamol for more
      than 24 hours during febrile illness, and to treat with NAC when transaminase
      levels are elevated. Paracetamol overdose during pregnancy should be treated with
      either oral or intravenous NAC according to the regular protocols in order to
      prevent maternal, and potentially fetal, toxicity. Unless severe maternal
      toxicity develops, paracetamol overdose does not appear to increase the risk for
      adverse pregnancy outcome.

PMID- 11444724
TI  - Behavioural effects of the new anticonvulsants.
AB  - Of the 9 new anticonvulsants that have been marketed recently in the UK or US, a
      number appear to have either adverse or beneficial effects on behaviour. There is
      now a considerable database of information, in terms of the number of patients
      treated and/or the number of published reports, on vigabatrin, lamotrigine,
      gabapentin and topiramate. Oxcarbazepine has been available in some centres for
      several years and there is extensive experience with the drug in Scandinavia. It
      appears that the profile of adverse and beneficial effects is similar to that of
      carbamazepine. Behavioural effects have probably been greatest with vigabatrin,
      with psychosis, depression and other behavioural problems recorded, but the use
      of this drug has been limited because of the concern about visual field
      constriction. The cognitive and behavioural effects of topiramate have caused
      concern, but these may be much less of a problem if lower starting dosages and
      escalation rates are used. Psychosis and depression have been associated with
      topiramate, as they have with another carbonic anhydrase inhibiting drug,
      zonisamide. Although zonisamide has been used for many years in Japan and Korea,
      experience elsewhere with this drug is currently very limited. Gabapentin seems
      to be less associated with adverse behavioural effects than some of the other new
      anticonvulsant drugs. The reports of behavioural disturbance with gabapentin in
      children may be related to dose escalation. Behavioural disturbance as a direct
      result of lamotrigine seems to be uncommon, although indirect effects on
      behaviour, through the so-called 'release phenomenon' from improved seizure
      control and consequent ability to misbehave, can occur. Positive behavioural
      effects have been described with several of the new anticonvulsants, particularly
      gabapentin, lamotrigine and oxcarbazepine; all of these drugs may have mood
      levelling effects that could be of value in treating affective disorders. The
      information on tiagabine and levetiracetam is too limited to allow any firm
      conclusions to be drawn with regard to positive or negative behavioural effects.
      When interpreting reports of behavioural changes with anticonvulsants, it is
      important to avoid attributing the effect to the drug when one or more of the
      other multiple causes of behavioural disturbance in people with epilepsy may be
      responsible or when an indirect effect such as 'forced normalisation' may be the
      cause. Many of the published studies are retrospective and unblinded rather than
      double-blind, placebo-controlled, prospective trials, implying that much of the
      data must be interpreted with caution at this stage.

PMID- 11444725
TI  - Comparative tolerability of pharmacological treatments for patent ductus
      arteriosus.
AB  - The ductus arteriosus is a vascular channel which, although vital to the fetal
      circulation, rapidly becomes unnecessary and even deleterious after birth. As
      such, it is 'preprogrammed' to constrict within the first few hours of life. In
      infants born prematurely this natural closure is often delayed and/or
      ineffective. In this review, we summarise the current knowledge of the delicately
      orchestrated control of normal ductal closure, with emphasis on the role of
      various biochemical mediators. The major focus of this review, however, is on
      pharmacological approaches designed to prevent and/or treat the persistently
      patent ductus arteriosus (PDA) which often fails to constrict spontaneously in
      the premature infant. The standard treatment regimen is based on the
      administration of 3 doses of the nonselective cyclo-oxygenase inhibitor,
      indomethacin. We begin by examining, from the vantage point of the ductus, the
      use of this indomethacin as a tocolytic. It seems that antenatal administration
      of indomethacin can cause transient, reversible ductus constriction which renders
      the post-treatment ductus resistant to subsequent closure, both natural and
      therapeutic. We then review some of the pros and cons associated with the
      prophylactic administration of indomethacin. Although prophylactic indomethacin
      is aimed primarily at preventing intraventricular haemorrhages in premature
      neonates, it does tend to reduce the risk of PDA as well. We then describe some
      novel therapeutic approaches to effect ductal closure with indomethacin,
      including the use of continuous infusions to minimise toxic vasoconstrictive
      phenomena and the use of prolonged maintenance dose to prevent PDA recurrences.
      Finally we discuss some of the newer agents described more recently which play a
      role in closing the persistently patent ductus over the next decade. Most
      prominent of these is ibuprofen which some studies have shown to have less
      undesirable vasoconstrictive adverse effects. Studies which compare the use of
      ibuprofen to indomethacin are summarised.

PMID- 11444727
TI  - Transvaginal sonographic evaluation of fetal anatomy at 14 to 16 weeks. Why is
      this technique not attractive in the United States?

PMID- 11444726
TI  - Drug treatment for tuberculosis during pregnancy: safety considerations.
AB  - Untreated tuberculosis in pregnancy poses a significant threat to the mother,
      fetus and family. Adherence to treatment is especially difficult in pregnancy
      because of the general fear of any medication and pregnancy-related nausea.
      Supervised treatment is especially helpful in encouraging adherence. All 4 first
      line drugs [isoniazid, rifampicin (rifampin), ethambutol and pyrazinamide] have
      an excellent safety record in pregnancy and are not associated with human fetal
      malformations. Drug-induced hepatitis, especially with isoniazid, is a
      significant problem in treating tuberculosis, not peculiar to pregnancy; close
      monitoring of liver function is recommended. Liver enzyme induction by rifampicin
      alters the metabolism of other drugs, e.g. methadone doses will need to be
      increased. Streptomycin should not be used in pregnancy, as perhaps 1 in 6 babies
      will have problems with hearing and/or balance. Ciprofloxacin has the best safety
      profile of second line drugs in the treatment of drug-resistant tuberculosis.
      Preventive treatment with isoniazid can be undertaken safely during pregnancy.
      Pyridoxine (vitamin B6) should be added to the drug treatment of tuberculosis in
      all pregnant women taking isoniazid. Neither tuberculin nor the bacille Calmette
      Guerin (BCG) vaccine are treatments for tuberculosis, but they play an important
      role in the management of the disease. Tuberculin testing is safe, but BCG
      vaccination should be avoided in pregnancy and instead given earlier in life.

PMID- 11444728
TI  - Transvaginal sonographic evaluation of fetal anatomy at 14 to 16 weeks. Why it is
      not feasible in the United States.

PMID- 11444729
TI  - Analysis of three-dimensional Doppler ultrasonographic quantitative measures for
      the discrimination of prostate cancer.
AB  - OBJECTIVE: The purpose of this study was to determine whether several
      quantitative ultrasonographic measures have potential to discriminate prostate
      cancer from normal prostate and to determine the best combination of these
      measures. The true spatial distributions of cancer within the prostates studied
      were obtained histologically after radical prostatectomy. The relationship
      between Doppler ultrasonography and microvessel count was also investigated.
      METHODS: Three-dimensional Doppler ultrasonographic data were acquired from 39
      patients before radical prostatectomy. The removed prostate was sectioned, and
      whole-mount hematoxylineosin-stained slides were used to identify all regions of
      cancer within each prostate. These histologic and ultrasonographic data were
      spatially registered. Doppler ultrasonographic measures were calculated within
      uniformly sized three-dimensional regions that were either entirely cancerous or
      noncancerous, and receiver operating characteristic analysis was performed on the
      results. Microvessel counts were made within each contiguous cancerous region and
      correlated with ultrasonographic measures. RESULTS: Color pixel density was the
      best simple measure for discriminating prostate cancer (accuracy, 80%). The mean
      power mode value (normalized mean power in color pixels) was inversely related to
      cancer with an accuracy of 1--normalized mean power in color pixels = 65% (low
      mean power is more cancerous). When color pixel density was combined with the
      normalized mean power in color pixels, its accuracy improved slightly to 84%. The
      peak microvessel count had a negative correlation with color pixel density as
      well as with cancer stage. CONCLUSION: Doppler ultrasonography does provide
      discriminatory information for prostate cancer, with color pixel density being
      the most promising measure.

PMID- 11444730
TI  - Deferoxamine-induced dysplasia of the knee: sonographic features and diagnostic
      performance compared with magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the features and diagnostic performance of sonography in
      the assessment of deferoxamine-induced dysplasia of the knee. METHODS: The left
      knees of 32 patients with thalassemia who were receiving regular blood
      transfusions and chelation therapy were studied with sonography for signs of
      deferoxamine-induced bone dysplasia. Abnormal physeal and metaphyseal changes
      detected on sonography included notching at the metaphyseal corner, a blurred or
      irregular peripheral juxtaphyseal metaphyseal contour, and widening of the
      peripheral juxtaphyseal metaphyseal echogenic interface. The accuracy of
      sonography in diagnosing dysplasia was evaluated by using magnetic resonance
      imaging as the standard of reference. RESULTS: There were 14 true-positive
      findings, 10 true-negative findings, 7 false-negative findings, and 1 false
      positive sonographic diagnosis of dysplasia, giving 67% sensitivity, 91%
      specificity, a 93% positive predictive value, and a 59% negative predictive
      value. CONCLUSION: Sonography was specific but only moderately sensitive in the
      diagnosis of deferoxamine-induced dysplasia at the knee when compared with
      magnetic resonance imaging.

PMID- 11444731
TI  - Hydatid liver cyst: an 11-year experience of treatment with percutaneous
      aspiration and ethanol injection.
AB  - OBJECTIVE: To report an 11-year experience of treatment of hydatid liver cysts
      with double percutaneous aspiration and injection of alcohol. METHODS: Of the 129
      patients with 174 hydatid liver cysts admitted to our department between January
      1988 and January 1999, 79 patients with 119 vital hydatid liver cysts were
      selected for double percutaneous aspiration and injection of alcohol. Under
      ultrasonographic guidance, cystic cavities were first drained through fine
      needles, and then 95% sterile ethanol was injected and left in situ. The same
      procedure was repeated 3 days later without reaspiration of the injected alcohol.
      General anesthesia without endotracheal intubation was performed in 21 selected
      cases. RESULTS: Double percutaneous aspiration and injection of alcohol was
      completed in 78 patients with 118 hydatid liver cysts. In 1 case the procedure
      could not be accomplished because of an intracystic hemorrhage. A total of 254
      punctures were performed, and the ethanol injected per session ranged between 12
      and 250 mL. The mean hospital stay was 2.9 days (range, 2-7 days). The overall
      median follow-up was 48 months (range, 6-122 months). At the last
      ultrasonographic examination, 45.8% of the treated hydatid liver cysts had a
      solid pattern, 47.4% were no longer appreciable, and 6.8% had a minimal liquid
      component. Intracystic relapse occurred in 5% of the patients. In no case were
      any new cysts observed either in different hepatic segments or in any
      extrahepatic location. The morbidity rate was 9%, and 1 death occurred (mortality
      rate, 1.3%). CONCLUSIONS: Over a long period, double percutaneous aspiration and
      injection of alcohol proved to be a substantially safe, effective, and low-cost
      procedure for hydatid liver cyst treatment.

PMID- 11444732
TI  - Sonographic evaluation of anatomic results after the pubovaginal sling procedure
      for stress urinary incontinence.
AB  - OBJECTIVE: To investigate the anatomic changes after the pubovaginal sling
      procedure in women with stress urinary incontinence by transrectal sonography
      METHODS: This study enrolled 56 women with varying types of stress urinary
      incontinence who were treated with the pubovaginal sling procedure using self
      fashioned polypropylene mesh. The suburethral sling was fixed without tension and
      was placed at the position between the bladder neck and the proximal urethra. The
      patients were investigated preoperatively and postoperatively by transrectal
      sonography of the bladder and urethra. RESULTS: At a median follow-up of 24
      months (range, 6-39 months), 48 patients (85.7%) were cured, 6 (10.7%) had
      improved, and 2 (3.6%) had treatment failures. Transrectal sonography revealed a
      well-suspended bladder neck and proximal urethra in all patients who were cured.
      As measured by changes of the axis of the pubovesical ligament, the position of
      the bladder neck was elevated by a mean of 29.6 +/- 21.5 degrees in the resting
      condition and 47.4 +/- 27.7 degrees in the straining condition. An incompetent
      bladder neck and proximal urethra were noted in 8 patients who had stress urinary
      incontinence after surgery. The incidence of opening of the bladder neck was
      84.6% in 13 patients with de novo urgency or urge incontinence, whereas only 2
      (4.7%) of 43 patients who did not have postoperative urgency had opening of the
      neck (P = .000). CONCLUSION: Transrectal sonography provides useful information
      about anatomic changes after the pubovaginal sling procedure. Bladder neck
      incompetence after surgery was closely related to postoperative urgency or urge
      incontinence.

PMID- 11444733
TI  - Sonographically guided renal mass biopsy: indications and efficacy.
AB  - PURPOSE: To review the clinical indications, pathologic results, and success rate
      of all our sonographically guided solid renal mass biopsies over a 5-year period.
      METHODS: Between 1993 and 1998, 44 consecutive patients underwent sonographically
      guided percutaneous biopsy of a solid renal mass. Indications included prior
      history of nonrenal malignancy, metastatic disease of unknown primary origin,
      previous contralateral nephrectomy for a renal cell neoplasm, a renal transplant
      mass, suspected renal lymphoma, history of tuberous sclerosis, and poor surgical
      candidacy. Aspiration biopsies were initially performed with 22- to 18-gauge
      spinal needles. If the initial cytologic evaluation findings were nondiagnostic,
      core biopsies were then performed with 20- to 18-gauge core biopsy guns. Dictated
      sonographic reports of the biopsies were reviewed to determine the following:
      indication for biopsy, location and size of the renal mass, needle gauge and
      type, number of needle passes, and complications. Final cytologic and surgical
      pathologic records were reviewed. RESULTS: Thirty-six (82%) of the 44 biopsy
      specimens were diagnostic. Aspirated smears were diagnostic in 24 (67%) of these
      cases, with the diagnosis made on the basis of cell block alone in an additional
      2 (6%). A definitive diagnosis came from core biopsy alone in 10 cases (28%). The
      18-gauge core needle yielded diagnostic results more reliably than the 20-gauge
      core needle, and a significant correlation was seen between core biopsy needle
      size and the rate of diagnostic core samples (P = .017). Pathologic diagnoses
      included renal cell carcinoma (n = 18), lymphoma (n = 4), oncocytic neoplasm (n =
      4), transitional cell carcinoma (n = 2), angiomyolipoma (n = 1), papillary
      cortical neoplasm (n = 1), and metastatic carcinoma (n = 6). Complications were
      seen in 4 (9%) of 44 cases; all were treated conservatively. CONCLUSIONS: For
      specific clinical indications, sonographically guided fine-needle aspiration and
      core biopsy of a solid renal mass can be performed safely. In many cases, a
      definitive diagnosis can be made on the basis of fine-needle aspiration alone.
      However, diagnosis may ultimately require core biopsy, for which 18-gauge core
      needles would be more reliably diagnostic than 20-gauge needles.

PMID- 11444734
TI  - Frequency of a monochorionic pair in multiple gestations: relationship to mode of
      conception.
AB  - OBJECTIVE: To determine whether the mode of conception affects the frequency of
      monochorionicity in multiple gestations. METHODS: Our study population consisted
      of all women with multiple gestations who had a first-trimester sonogram at our
      institution between May 1998 and April 2000. The frequency of monochorionicity in
      pregnancies conceived naturally was compared with the frequency in pregnancies
      achieved via any form of assisted reproductive technology and among the different
      types of assisted reproductive technology. RESULTS: Our study consisted of 464
      multiple gestations comprising 332 twin, 113 triplet, 16 quadruplet, and 3
      quintuplet pregnancies. The higher the fetal number, the more likely the
      pregnancy resulted from assisted reproductive technology (72.6% of twins, 84.1%
      of triplets, 92.8% of quadruplets, and 100% of quintuplets; P < .05, Fisher exact
      test). Monochorionic pairs were found more commonly in naturally conceived
      pregnancies than in those resulting from assisted reproductive technology (28.2%
      versus 5.4%; P < .000001, chi2 test). The frequency of monochorionic pairs after
      in vitro fertilization with blastocyst transfer on day 5 (10.5%) was double the
      frequency from in vitro fertilization with cleavage stage transfer on day 3
      (4.9%), but the difference was not statistically significant (P = .24, Fisher
      exact test). CONCLUSIONS: Monochorionic pairs are relatively common in naturally
      conceived twins and in higher-order multiple gestations with more than 3 fetuses
      arising from assisted reproductive technology, but they are uncommon in twins and
      triplets arising from assisted reproductive technology There is a trend toward a
      higher frequency of monochorionic pairs after day 5 blastocyst transfer than day
      3 transfer, but a larger study population is needed to confirm this finding.

PMID- 11444735
TI  - Fetal intracardiac echogenic foci: visualization depends on the orientation of
      the 4-chamber view.
AB  - OBJECTIVE: To compare the frequency of visualization of echogenic intracardiac
      foci in different cardiac views. METHODS: Women having ultrasonographic
      examinations between October 1997 and July 1998 were prospectively evaluated if a
      fetal echogenic intracardiac focus was seen in either ventricle. RESULTS:
      Echogenic intracardiac foci were seen in 89 fetuses in whom both the apical and
      lateral 4-chamber heart views were obtained. Eight-six fetuses (97%) had a single
      focus (83 in the left ventricle and 3 in the right ventricle), and 3 (3%) had 2
      foci. Echogenic intracardiac foci were seen in the apical 4-chamber view in 89
      (100%) and in the lateral 4-chamber view in only 26 (29%; P = .001). CONCLUSIONS:
      Echogenic intracardiac foci are not easily seen in the lateral 4-chamber view.
      Studies that suggest an increased risk of aneuploidy when echogenic foci are seen
      should specify the orientation of the 4-chamber view used.

PMID- 11444736
TI  - Shape reconstruction of the left ventricle: accuracy of limited-plane three
      dimensional echocardiography.
AB  - OBJECTIVE: To assess the accuracy of left ventricular cavity shape reproduction
      from 8 spatially related, apical two-dimensional ultrasonographic images.
      METHODS: We scanned 6 dog heart specimens. Left ventricular cavity casts were
      reconstructed from 48-tomogram (high-density), 8-tomogram (octaplane), and 2
      tomogram (low-density biplane) apical data sets. The 48-plane left ventricular
      cast served as the reference. Spatial shape resolution of 3 mm in radial distance
      from the rotational axis to the interpolated endocardium was used as the
      criterion of shape accuracy. RESULTS: The adjusted limits of agreement for the
      octaplane and biplane left ventricular casts were +/-2.31 and +/-6.84 mm,
      respectively. CONCLUSIONS: The three-dimensional left ventricular cavity shape
      can be accurately reproduced by using a low-data density apical octaplane
      echocardiographic examination.

PMID- 11444737
TI  - Sonographic screening for fetal aneuploidy: first trimester.
AB  - OBJECTIVES: Screening for fetal aneuploidy is now possible during the first
      trimester using sonographic and biochemical markers. The aim of this review was
      to summarize the efficacy and use of nuchal translucency in screening for fetal
      aneuploidy, especially fetal Down syndrome, and other anomalies. METHODS: We
      reviewed available literature regarding first-trimester screening. This includes
      more than 16 studies of nuchal translucency as a marker for fetal aneuploidy
      published since 1995. RESULTS: Although early studies showed wide variation in
      detection of fetal Down syndrome when using nuchal translucency, more recent
      studies showed sensitivities of approximately 70% to 80%, for a 5% false-positive
      rate. Increased nuchal translucency has also been found to be a marker for other
      aneuploidies, including trisomy 18, trisomy 13, and Turner syndrome. Maternal
      serum biochemical screening can be used as a test for aneuploidy during the first
      trimester The 2 maternal serum markers that appear to be most useful in the late
      first trimester are the free beta subunit of human chorionic gonadotropin and
      pregnancy-associated plasma protein A. Together with maternal age, these markers
      yield a detection rate for trisomy 21 of approximately 60%, for a 5% false
      positive rate. Because sonographic and biochemical markers appear to be largely
      independent, their combined risk results in improved detection rates compared
      with either method alone. As a result, the combination of nuchal translucency,
      biochemical markers, and maternal age has achieved a detection rate of
      approximately 85%, for a 5% false-positive level for detection of trisomy 21. A
      newly proposed "integrated" approach using a panel of first- and second-trimester
      markers suggests that further improvement in the screening performance is
      possible. A number of questions regarding first-trimester screening remain. We
      address some of these questions: is first-trimester screening more effective than
      second-trimester screening? How to account for intrauterine lethality? Is earlier
      diagnosis important, and will it be accepted by patients? Is first-trimester
      screening cost-effective? How should first-trimester screening be interpreted
      with second-trimester tests? CONCLUSIONS: Despite encouraging data and general
      enthusiasm for first-trimester screening for fetal Down syndrome and other
      aneuploidies, a number of questions remain about its implementation in the United
      States. Multicenter studies currently under way should help answer some of these
      questions.

PMID- 11444738
TI  - Retroperitoneal abscess and mycotic aortic aneurysm: unusual septic complications
      of central vascular line placement in premature infants.
AB  - OBJECTIVE: To describe the sonographic appearance of unusual septic complications
      after central vascular line placement in premature infants. METHODS: Two case
      reports are presented. RESULTS: The first patient had a retroperitoneal abscess
      after percutaneous central venous catheter placement. The second patient had a
      ruptured mycotic aneurysm of the abdominal aorta after umbilical arterial
      catheter placement. CONCLUSIONS: Retroperitoneal abscess and aortic aneurysm
      should be considered in patients with histories of long-standing catheters or
      line sepsis. Both of these complications are readily diagnosed on the basis of
      sonography.

PMID- 11444739
TI  - Color Doppler and duplex sonography in 5 patients with thoracic outlet syndrome.
AB  - PURPOSE: To evaluate the use of color Doppler sonography in the diagnosis of
      thoracic outlet syndrome. METHODS: We studied color Doppler sonographic findings
      in 5 clinically suspected cases of thoracic outlet syndrome. The subclavian
      artery and vein were studied in varying degrees of abduction to assess the
      severity of the syndrome. RESULTS: Significant changes, i.e., stages of increased
      velocities, preocclusion, and occlusion in the subclavian artery in varying
      degrees of abduction, were noted in 4 of 5 cases. Blunted flow in the axillary
      artery (4 patients) and a rebound increase in velocities on release of abduction
      were noted in 3 patients. These changes suggested that significant narrowing was
      causing symptoms. CONCLUSION: Color Doppler sonography is a noninvasive,
      effective method compared with digital subtraction angiography in the diagnosis
      of thoracic outlet syndrome.

PMID- 11444740
TI  - Tubal ring and corpus luteum echogenicities.

PMID- 11444741
TI  - Fetal craniopharyngioma: early prenatal diagnosis.

PMID- 11444742
TI  - Right-sided diverticulitis mistaken for appendicitis on ultrasonography in a 21
      year-old man.

PMID- 11444743
TI  - Hand-assisted laparoscopic distal gastrectomy with regional lymph node dissection
      for gastric cancer.
AB  - Recently, a minimally invasive operation for gastric malignancies has been
      advocated, and the laparoscopic operation is noted as a technique that raises the
      quality of life. We performed distal gastrectomy with regional lymph node
      dissection by hand-assisted laparoscopic surgery for 60 cases of gastric cancer
      located in the middle or lower third of the stomach. Billroth I reconstruction
      was applied intracorporeally to the first 30 cases by using the double stapling
      method with a conventional circular stapling device, and in the final 30 cases,
      the quadrilateral (square) stapling technique with a laparoscopic linear stapling
      device was used to prevent postoperative anastomotic bleeding. This technique not
      only is less invasive, but also is similarly curative compared with open
      gastrectomy that was performed for 60 gastric cancer cases of similar staging
      before the beginning of this procedure.

PMID- 11444744
TI  - Palliation of malignant gastric outlet obstruction caused by gastric cancer with
      self-expandable metal stents.
AB  - Gastric carcinoma is among the most common cancers worldwide. Surgery remains the
      mainstay of potentially curative treatments. Unfortunately, most patients have an
      advanced form of the disease. We evaluated our experience in palliating malignant
      gastric outlet obstruction caused by gastric cancer with expandable metal stents
      (Wallstent Enteral; Boston Scientific, Singapore). Six patients with a median age
      of 68 years (range, 45-88) underwent the procedure. Three had metastatic gastric
      cancer; two recurrent gastric cancer; and one locally advanced gastric cancer
      with poor comorbid status. After the procedure, five of the six patients were
      able to resume an oral feeding within 24 hours. One patient with gastric
      dysmotility caused by linitus plastica required nasogastric tube feeding. Three
      patients died during a median follow-up period of 4 weeks (range, 2-8). The other
      three patients were still well at a median follow-up period of 10 weeks (range, 5
      12). There was no procedure-related mortality or morbidity, nor was there any
      stent migration or blockage in any of these patients. In conclusion, palliation
      of malignant gastric outlet strictures caused by gastric cancer with expandable
      metal stents is an effective and safe alternative to surgery, particularly in
      patients with postgastrectomy anastomotic recurrence and in those who are poor
      candidates for surgery. Patients who are not expected to survive beyond 1 month
      and those with linitus plastica and associated gastric dysmotility may not be
      appropriate candidates for such a procedure.

PMID- 11444745
TI  - Cirrhosis and laparoscopic cholecystectomy.
AB  - Although cirrhosis has been regarded as a contraindication to laparoscopic
      cholecystectomy, there is increasing evidence that patients with mild to moderate
      cirrhosis may safely undergo laparoscopic cholecystectomy with results superior
      to those of open cholecystectomy. A prospective evaluation and comparison of
      outcome in 25 consecutive patients with cirrhosis and 1275 patients without
      cirrhosis undergoing laparoscopic cholecystectomy was undertaken. Fourteen
      patients with Child's A cirrhosis, nine with Child's B, and two with Child's C
      underwent laparoscopic cholecystectomy. After surgery, one patient with Child's C
      cirrhosis died. The median length of stay was 4 days. Postoperative morbidity
      occurred in 52% of patients and included hemorrhage (8%), thromboembolism (4%),
      wound complications (24%), intraabdominal collections (12%), and cardiopulmonary
      complications (8%). Major comorbidity was present in 60% of patients and
      contributed to complication rate and prolonged stay. Hemorrhage (P = 0.04) and
      wound complications (P = 0.02) occurred more frequently in patients with
      cirrhosis than in patients without cirrhosis. Laparoscopic cholecystectomy in
      patients with cirrhosis is associated with significant but acceptable morbidity
      and mortality rates, and complications are frequently related to comorbid
      conditions.

PMID- 11444746
TI  - The benefits of a second transhepatic route in failed percutaneous management of
      difficult intrahepatic biliary strictures with recurrent hepatolithiasis.
AB  - Percutaneous stricture dilatation and cholangioscopic lithotomy has become a
      mainstay in the treatment of patients with recurrent hepatolithiasis associated
      with intrahepatic biliary strictures. In a consecutive series of 125 patients who
      underwent percutaneous management of recurrent hepatolithiasis from 1987 to 1999,
      there were 15 patients in whom the procedure failed to clear the stones. A second
      percutaneous transhepatic route was established for subsequent treatment. A
      reappraisal of its indications and efficacy was done. Treatment through a second
      route was helpful for patients with bilateral strictures, angulated duct,
      difficult strictures, large impacted stones, a subcutaneous jejunal limb, or
      hemobilia developing in the first route. Strictures remained impacted in 1 of the
      15 patients (failure rate, 7%), with the remaining having complete clearance of
      stones. Cholangitis occurred in two patients; no other complications were
      encountered. A second percutaneous route is very helpful for the management of
      complicated hepatolithiasis and biliary stricture.

PMID- 11444747
TI  - Laparoscopic cholecystectomy for polypoid lesions of the gallbladder: a
      clinicopathologic study.
AB  - The size and number of gallbladder polyps are used to differentiate between
      benign and malignant lesions before surgery and to determine whether surgery is
      necessary for the lesion. Since 1987, laparoscopic cholecystectomy has been
      widely used as the management method of choice for gallbladder lesions. The
      results of a clinicopathologic study of polypoid lesions of the gallbladder,
      based completely on laparoscopically resected gallbladder tissue, have not yet
      been evaluated fully. Data from 123 patients with polypoid lesions of the
      gallbladder treated by laparoscopic cholecystectomy were reviewed
      retrospectively. The gallbladders were classified into four histologic groups.
      Clinical features, maximal diameter, and the number of lesions were compared
      among the groups. The mean age of patients with adenoma and cancer was
      significantly greater than that of patients with cholesterol polyps and other
      lesions. More women than men had a neoplasm (adenoma and cancer). Patients in the
      neoplasm group tended to have a single lesion. The mean maximal diameter of
      neoplasms was significantly larger than that of lesions in the nonneoplasm group.
      All seven malignant lesions that were detected measured at least 1.5 cm.
      Univariate analysis showed that polypoid lesions of the gallbladder with
      neoplastic lesions correlated significantly with age, sex, size, and number of
      the lesions. Univariate analysis also showed that malignancy in polypoid lesions
      of the gallbladder correlated significantly with age, size, and number of the
      lesions. Multivariate logistic regression analysis showed that the age of the
      patient and the size of the lesion (> or = 1.0 cm) are two independent factors in
      predicting neoplastic lesions in polypoid lesions of the gallbladder. The size of
      the lesion (> or = 1.5 cm) is the only independent factor in predicting
      malignancy in the polypoid lesions of the gallbladder as shown by multivariate
      logistic regression analysis. Laparoscopic cholecystectomy is a safe and feasible
      method for gallbladder polypoid lesions. Neoplastic change in polypoid lesions of
      the gallbladder should be considered when a patient older than 50 years of age
      has a polypoid lesion larger than 1.0 cm. Cancer should be suspected when a
      polypoid lesion of the gallbladder is larger than 1.5 cm, and an aggressive
      surgical approach is warranted so that early gallbladder cancer can be detected
      and patients can have an increased chance of cure.

PMID- 11444748
TI  - Cost-effectiveness of ambulatory laparoscopic cholecystectomy.
AB  - The merits of laparoscopic cholecystectomy include faster recovery, less
      postoperative pain, earlier return to work, and decreased cost. However, there
      are few economic data comparing laparoscopic cholecystectomy in an ambulatory
      versus overnight stay setting. In a 12-month period, 74 consecutive
      cholecystectomies were performed laparoscopically by one surgeon. The ambulatory
      group consisted of 36 patients who were discharged from the hospital the same day
      after a mean recovery time of 5 hours (range, 2.25-10.33). Of the remaining 38
      patients, 19 were admitted after surgery on 23-hour observation status, and 19
      were inpatients. The average hospital cost was significantly less in the
      ambulatory group than in the observation group, with an 11% mean reduction in
      cost per patient (P = 0.0061). No patient in either group was readmitted to the
      hospital within 30 days of surgery. Laparoscopic cholecystectomy can be performed
      safely in an outpatient setting. The cost savings of ambulatory care versus
      observation are clearly shown in this study.

PMID- 11444749
TI  - Laparoscopic transcystic sphincter of Oddi manometry is not affected by carbon
      dioxide pneumoperitoneum.
AB  - Sphincter of Oddi (SO) dysfunction as a potential cause of chronic acalculous
      cholecystitis (CAC) has not been studied in cases for which intraoperative SO
      manometry was used during laparoscopic cholecystectomy. In this study, we
      evaluated the effects of carbon dioxide pneumoperitoneum on laparoscopic
      transcystic SO manometry. In 27 patients with CAC, transcystic SO manometry had
      been attempted during laparoscopic cholecystectomy. The mean age of the patients
      was 46 years (range, 22-71). Complete manometric data sets were obtained in 18
      patients. The mean SO pressure, phasic SO pressure, and phasic frequency were
      35.4 +/- 29.1 mm/Hg versus 30.8 +/- 23.8 mm/Hg, 104.8 +/- 63.0 mm/Hg versus 73.6
      +/- 34.6 mm/Hg, and 2.1 +/- 1.8 contractions/min versus 2.8 +/- 3.4
      contractions/min with and without pneumoperitoneum, respectively. All differences
      were nonsignificant (P > 0.05). Two complications (7.4%) were observed:
      pancreatitis and jaundice. SO manometry is not affected by CO2 pneumoperitoneum.
      It may be used to study SO motility in patients with CAC.

PMID- 11444750
TI  - A comparison of an open and laparoscopic appendectomy for patients with liver
      cirrhosis.
AB  - Liver cirrhosis is a critical factor contributing to morbidity and mortality in
      abdominal surgery, because patients with cirrhosis have a particularly high risk
      of developing bleeding, infection, and ascites. Laparoscopic appendectomy (LA)
      recently has gained a lot of attention around the world; however, comparisons
      between the benefits of LA and those of conventional open appendectomy (OA) for
      patients with liver cirrhosis have yet to be sufficiently compiled. In the
      present retrospective study, 40 patients with liver cirrhosis who were diagnosed
      with acute appendicitis before surgery underwent an appendectomy (OA in 25
      patients and LA in 15 patients). This study focused on the operative time, amount
      of postoperative pain, use of analgesics, the restart of a normal diet, number of
      complications, length of hospital stay, and cost-effectiveness of the procedure
      in such patients. The amount of postoperative pain and the length of hospital
      stay were significantly smaller in the LA group. The mean values of the serum C
      reactive protein on postoperative days 1, 3, and 7 were significantly less in the
      LA group. The number of wound infections and wound bleeding was also less in the
      LA group. The difference in the total cost of hospitalization was not
      significant. The cost of the operation was greater in the LA group than in the OA
      group, whereas the hospitalization cost in the LA group was less than that in the
      OA group. The results of this study suggest that LA may be superior to OA for the
      treatment of postoperative pain and postoperative complications for patients with
      liver cirrhosis. Long-term follow-up studies are still necessary, however, to
      determine any possible decrease in the number of late complications.

PMID- 11444751
TI  - Endoscopic localization and management of colonic bleeding in patients with
      portal hypertension.
AB  - In patients with portal hypertension, vascular lesions in the colon may develop
      that have been collectively termed portal hypertensive colopathy. Endoscopic
      diagnosis of these lesions is now established, but the management of hemorrhage
      from them is not. We report five cases of endoscopic management of bleeding
      colonic vascular lesions in patients with portal hypertension. Endoscopy data
      from January 1, 1996 to June 30, 1999 identified 158 patients with portal
      hypertension who underwent colonoscopy. Forty-five of these 158 patients had
      portal hypertensive colopathy (angiodysplasias or varices). Those who had
      colonoscopic hemostasis attempted were identified and reviewed. Five patients
      underwent colonoscopic intervention for bleeding. Initial hemostasis was achieved
      in four of five cases. Repeat endoscopic intervention was necessary in three of
      the four cases. One patient required surgery. In patients with portal
      hypertension, colonic vascular lesions may develop. Hemorrhage from these lesions
      is rare. Colonoscopy is effective for localization and diagnosis of bleeding
      vascular lesions and permits simultaneous hemostatic intervention.

PMID- 11444752
TI  - Stapled laparoscopic gastropexy for paraesophageal hernia.
AB  - A minimally invasive correction of symptomatic paraesophageal hernia in high-risk
      elderly patients is described with an emphasis on a new method of laparoscopic
      gastropexy that is simple, reliable, and can be performed rapidly.

PMID- 11444753
TI  - Laparoscopic pancreatic cystgastrostomy: the lesser sac technique.
AB  - Management of pancreatic pseudocysts has remained largely unchanged during the
      past century. Excision and drainage procedures remain the mainstay of therapy for
      large, persistent, or symptomatic pseudocysts. Laparoscopic approaches to the
      management of pancreatic pseudocysts have been previously described. The lesser
      sac approach is an effective means of creating a hemostatic cystgastrostomy
      through a single posterior gastrotomy. This procedure is performed by creating a
      cystotomy and posterior wall gastrotomy through which an endoscopic stapler is
      applied. The cystotomy-gastrotomy is closed using laparoscopically placed
      sutures. An endoscope is inserted into the stomach and pseudocyst at the
      conclusion of the procedure to ensure an airtight anastomosis. The lesser sac
      approach to pancreatic cystgastrostomy allows for a minimally invasive approach
      to the management of pancreatic pseudocysts using a single gastrotomy.

PMID- 11444754
TI  - Percutaneous treatment of gallstone abscess after laparoscopic cholecystectomy
      using fistuloscopy.
AB  - A 69-year-old man with a low-grade fever and right upper quadrant pain was
      diagnosed as having two gallstone abscesses after laparoscopic cholecystectomy.
      One lesion healed after stones spontaneously passed through the drainage tube,
      and the other lesion healed after percutaneous removal of stones using
      fistuloscopy. The patient's course was uneventful as of 29 months after
      percutaneous treatment.

PMID- 11444755
TI  - Superficial nerve damage of thumb of laparoscopic surgeon.
AB  - We report a case of digital nerve (superficial branch of the radial nerve)
      compression injury in the thumb caused by repeated compression at the proximal
      phalanx level by a finger grip of a laparoscopic instrument during laparoscopic
      surgery.

PMID- 11444756
TI  - Laparoscopic repair of traumatic diaphragmatic hernia.
AB  - Posttraumatic diaphragmatic rupture or eventration is still a challenging
      problem. Herein five cases of patients with such a diaphragmatic lesion treated
      successfully by laparoscopy are reported with a discussion of the advantages of
      this mini-invasive surgical approach.

PMID- 11444757
TI  - Endoscopically assisted pectus excavatum repair.
AB  - We present an endoscopic approach for the reconstruction of pectus excavatum with
      a custom silicone implant. The procedure incorporates endoscopic techniques to
      facilitate dissection of an extensive subcutaneous pocket through a 6-cm Chevron
      skin incision 8 cm below the level of the xiphoid. The incision is designed based
      on the size, shape, and flexibility of the custom implant and the configuration
      of the chest wall deformity. A superiorly based rectus abdominis anterior fascial
      sheath flap then is elevated up to the caudal-most margin of the implant,
      creating a sling below the implant, thus stabilizing its position and preventing
      direct communication with the overlying skin incision. In our patient, the
      endoscope permitted insertion of the custom implant while minimizing the length
      of incision. The cosmetic result using a minimally invasive approach to assist
      with the dissection was acceptable, and the morbidity and scarring were
      minimized.

PMID- 11444758
TI  - Segmental bronchial atresia of the left upper lobe treated with segmental
      resection under video-assisted thoracic surgery.
AB  - We report our experience of segmental bronchial atresia managed with segmental
      resection under video-assisted thoracic surgery. A 23-year-old woman reporting a
      cough, dyspnea, and back pain underwent segmental resection in which a stapling
      device was used under video-assisted thoracic surgery. Her postoperative course
      was uneventful with minimal pain and a disappearance of preoperative symptoms
      after surgery. Once an accurate preoperative diagnosis can be established, video
      assisted thoracic segmentectomy together with the use of a stapling device is
      considered to be feasible.

PMID- 11444759
TI  - Laparoscopic exclusion of a splenic artery aneurysm using a lateral approach
      permits preservation of the spleen.
AB  - Splenic artery aneurysms have commonly accepted therapeutic indications.
      Operative therapy for splenic artery aneurysms has traditionally consisted of
      aneurysm resection with a possible splenectomy. Recently, laparoscopic splenic
      artery aneurysm exclusion has been shown to provide adequate therapy without
      incurring the morbidity associated with aneurysmectomy and splenectomy. However,
      an anterior approach to exclusion may result in short gastric and left
      gastroepiploic artery disruption leading to splenic infarction. Preservation of
      the spleen can best be assured by a lateral approach, which preserves collateral
      splenic perfusion. A 51-year-old woman with a distal splenic artery aneurysm, who
      underwent an uncomplicated laparoscopic splenic artery aneurysm exclusion using a
      lateral approach, is described.

PMID- 11444760
TI  - Laparoscopic ligation of an aneurysm of the left gastric artery.
AB  - We describe the laparoscopic ligation of an aneurysm of the left gastric artery.
      The patient was admitted to the hospital with epigastric pain, and computed
      tomography showed a retroperitoneal hemorrhage. Celiac angiography showed a
      fusiform-type aneurysm 1.0 cm in diameter at the trunk of the left gastric
      artery. The left gastric artery was ligated at sites proximal and distal to the
      aneurysm under laparoscopy, and the patient's postoperative course was
      uneventful. Laparoscopic surgery appears useful for elective surgery of an
      aneurysm in the left gastric artery.

PMID- 11444761
TI  - Pharmacology of rapid-onset antidepressant treatment strategies.
AB  - Although selective serotonin reuptake inhibitors (SSRIs) block serotonin (5-HT)
      reuptake rapidly, their therapeutic action is delayed. The increase in synaptic 5
      HT activates feedback mechanisms mediated by 5-HT1A (cell body) and 5-HT1B
      (terminal) autoreceptors, which, respectively, reduce the firing in 5-HT neurons
      and decrease the amount of 5-HT released per action potential resulting in
      attenuated 5-HT neurotransmission. Long-term treatment desensitizes the
      inhibitory 5-HT1 autoreceptors, and 5-HT neurotransmission is enhanced. The time
      course of these events is similar to the delay of clinical action. The addition
      of pindolol, which blocks 5-HT1A receptors, to SSRI treatment decouples the
      feedback inhibition of 5-HT neuron firing and accelerates and enhances the
      antidepressant response. The neuronal circuitry of the 5-HT and norepinephrine
      (NE) systems and their connections to forebrain areas believed to be involved in
      depression has been dissected. The firing of 5-HT neurons in the raphe nuclei is
      driven, at least partly, by alpha1-adrenoceptor-mediated excitatory inputs from
      NE neurons. Inhibitory alpha2-adrenoceptors on the NE neuroterminals form part of
      a feedback control mechanism. Mirtazapine, an antagonist at alpha2-adrenoceptors,
      does not enhance 5-HT neurotransmission directly but disinhibits the NE
      activation of 5-HT neurons and thereby increases 5-HT neurotransmission by a
      mechanism that does not require a time-dependent desensitization of receptors.
      These neurobiological phenomena may underlie the apparently faster onset of
      action of mirtazapine compared with the SSRIs.

PMID- 11444762
TI  - Methodology to measure onset of action.
AB  - Onset of action has become one of the most topical issues in antidepressant
      therapy. In general, the speed of onset of action of antidepressants is regarded
      as too slow. Most patients who benefit from treatment require 2 or more weeks of
      therapy to show signs of response. Since the onset of therapeutic efficacy is of
      current interest to physicians and health authorities, the question arises of how
      to measure the onset of therapeutic efficacy. There are many different proposals
      for the statistical analysis of data to determine early onset of action. One of
      the most important considerations in analyzing early onset of action is the
      definition of criteria. Conventional approaches, such as the De Paula and Omer
      approach and the Huitfeldt and Montgomery approach, can provide useful
      information, although they do not take into account whether the early response is
      sustained. The use of pattern analyses does overcome the problem, but the
      generalizability of their findings is somewhat limited by their use of stringent
      exclusion criteria. Survival analyses can provide a more sensitive measure of
      early changes. Moreover, this method can easily be adapted to take into account
      sustained response and be used to restrict attention only to those subjects who
      achieve onset. In this article, the above-mentioned approaches will be explained
      with the help of some clinical examples to achieve a further understanding of the
      methodology of measuring onset of action.

PMID- 11444763
TI  - Do some antidepressants work faster than others?
AB  - The clinical utility of antidepressant drugs is impaired by the delay in onset of
      their therapeutic action. It is becoming increasingly clear that differences
      exist between antidepressants with respect to this property, both within and
      between pharmacologic classes. Post hoc analyses of comparisons between selective
      serotonin reuptake inhibitors and dual-action antidepressants such as mirtazapine
      and venlafaxine indicate that the dual-action drugs may have a faster onset of
      action. At least in the case of mirtazapine, the earlier onset appears to be via
      a specific antidepressant effect and not an effect on sleep or other accessory
      symptoms. Studies that compare mirtazapine and venlafaxine are relatively rare
      and lack sufficient statistical power to determine a difference in the onset of
      action. Although these differences have been shown in clinical efficacy studies
      not specifically designed to detect differences in onset of action, a definitive
      demonstration of early onset of action awaits the results of appropriately
      designed and powered clinical studies currently planned or in progress.

PMID- 11444764
TI  - Depression: the relevance of the time factor.

PMID- 11444765
TI  - The economic and social burden of depression.
AB  - Depressive disorders are a major public health problem. They occur frequently and
      produce severe suffering for those affected and for their families. They are
      ubiquitous and appear at all ages. The consequences of depressive disorders in
      terms of excessive mortality, disability, and secondary morbidity are grave.
      There are indications that the frequency of depressive disorders will increase in
      the years to come, for a variety of reasons, including demographic changes,
      extended life expectancy of people suffering from chronic physical disorders, and
      iatrogenic causes. The essential criterion for designating a condition as a major
      public health problem--that there should be an effective intervention that will
      diminish or eliminate the problem-has now also been met. Recent years have seen
      the development of a variety of new treatments that can be applied even in
      situations where highly specialized mental health staff are scarce. These
      developments make training in the use of new treatment methods of proven value
      and their wide application a public health priority and an ethical obligation.
      The presentation will discuss these issues on the basis of accumulated evidence
      and experience.

PMID- 11444766
TI  - Bornavirus and psychiatric disorders -- fact or fiction?

PMID- 11444767
TI  - Staphylococcus epidermidis biofilms: importance and implications.
AB  - The coagulase-negative staphylococci and, in particular, Staphylococcus
      epidermidis, have emerged as major nosocomial pathogens associated with
      infections of implanted medical devices. These organisms, which are among the
      most prevalent bacteria of the human skin and mucous membrane microflora, present
      unique problems in the diagnosis and treatment of infections involving biofilm
      formation on implanted biomaterials. Epidemiological data that address whether
      invasive S. epidermidis strains can be traced to commensal organisms or an
      endemic occurrence of distinct strains with enhanced virulence have important
      implications for the implementation of appropriate infection control measures. An
      extracellular polysaccharide adhesin represents a key virulence determinant in S.
      epidermidis and is required for biofilm formation. Production of this adhesin,
      which is encoded by the ica operon, is subject to phase variable regulation (ON <
      --> OFF switching). Recent advances in understanding the molecular events
      controlling polysaccharide adhesin synthesis and the potential clinical
      implications of its phase variable regulation are outlined. Further research in
      this area may contribute to the development of novel strategies for therapeutic
      intervention. Finally, in addition to antibiotic prophylaxis, preventive
      strategies to control S. epidermidis medical device-related infections are
      focusing on the development of improved biomaterials and physical electrical
      barriers to impede bacterial colonisation.

PMID- 11444768
TI  - Genotyping of European isolates of methicillin-resistant Staphylococcus aureus by
      fluorescent amplified-fragment length polymorphism analysis (FAFLP) and pulsed
      field gel electrophoresis (PFGE) typing.
AB  - A representative panel of 50 European MRSA isolates was subjected to genotype
      analysis by fluorescent amplified-fragment length polymorphism (FAFLP) and by
      macrorestriction pulsed-field gel electrophoresis (PFGE). Each isolate had a
      unique profile with FAFLP. To model genetic relationships within the continuing
      MRSA epidemic, cluster analysis of FAFLP data was made, revealing nine clone
      complexes of MRSA. Most of these were also found by PFGE. A number of isolates
      had FAFLP profiles significantly different from others, and might represent
      emerging epidemic strains. FAFLP analysis proved particularly suitable for
      surveillance of the MRSA epidemic at national and international levels.

PMID- 11444769
TI  - Invasion of murine respiratory epithelial cells in vivo by Burkholderia cepacia.
AB  - Pulmonary infections caused by Burkholderia cepacia are an important cause of
      morbidity and mortality in cystic fibrosis (CF) patients. Several features
      suggestive of invasion and intracellular sequestration of B. cepacia in CF are
      persistence of infection in the face of antibiotic therapy and a propensity to
      cause bacteraemic infections in patients with CF. A mouse respiratory challenge
      model was used to investigate the invasion phenotype of B. cepacia in vivo. After
      intratracheal inoculation, epidemic B. cepacia strains translocated from lung to
      liver and spleen; however, all bacteria were cleared from all organs within 7
      days. B. cepacia strains, irrespective of cable piliation, were capable of
      attaching to and then invading murine respiratory tract epithelial cells.
      Histopathological examination of lungs showed interstitial infiltrates comprised
      mainly of polymorphonuclear leucocytes and were associated with widened alveolar
      septa. Electron microscopy demonstrated B. cepacia within epithelial cells and
      pulmonary macrophages. This study provides support for in-vitro observations that
      B. cepacia strains from patients with CF adhere to and then invade respiratory
      epithelial cells. The invasion phenotype in B. cepacia may be an important
      virulence factor in CF infections.

PMID- 11444770
TI  - Cytopathic effects of outer-membrane preparations of enteropathogenic Escherichia
      coli and co-expression of maltoporin with secretory virulence factor, EspB.
AB  - Enteropathogenic Escherichia coli (EPEC) is an important aetiological agent of
      persistent infantile diarrhoea. EPEC pathogenicity is not mediated through known
      toxins and the role played by outer-membrane proteins (OMPs) in the initial
      adherence of the bacterium, intimate attachment to epithelial cells and
      ultimately in the effacement of the intestinal epithelium is being pursued
      vigorously. In this study of the different cellular fractions of the bacterium
      investigated, only the outer-membrane fraction was able to disrupt HEp-2 cells.
      The outer-membrane fraction was also found to be cytotoxic and caused actin
      accumulation around the periphery of the host cells. To understand the role of
      OMPs in pathogenesis, protein profiles of outer-membrane preparations of wild
      type and attenuated mutants lacking either the EPEC adherence factor (EAF) mega
      plasmid or EPEC attaching and effacing gene A (eaeA) coding for a 94-kDa OMP,
      intimin or EPEC secretory protein gene B (espB) coding for a 34-kDa translocated
      signal transducing protein were compared and correlated with their cytopathic
      effects. A 43-kDa protein seen along with intimin in the outer membrane of EPEC
      was identified as maltoporin, an E. coli outer-membrane porin normally expressed
      only in response to maltose in the growth medium. In the case of EPEC, not only
      was this regulation lost, but also the expression of maltoporin was found to be
      tightly coupled to the expression of the secretory virulence factor EspB.
      Maltoporin per se is not toxic, as evidenced by the treatment of HEp-2 cells with
      the outer-membrane preparation of E. coli DH5a grown in the presence of maltose
      and the significance of this pathogenic adaptation is not clear. However, when
      maltoporin and possibly other unidentified proteins were not present as a
      component of the outer-membrane preparation, as in the outer-membrane preparation
      of an espB-negative strain, cellular disruption as well as actin accumulation
      proceeded at a very slow rate even though the cytotoxic effects were comparable
      to those of the wild-type EPEC strains.

PMID- 11444771
TI  - Evidence for holin function of tcdE gene in the pathogenicity of Clostridium
      difficile.
AB  - Toxigenic strains of Clostridium difficile produce two large bacterial toxins
      called toxins A (TcdA) and B (TcdB). tcdA and tcdB genes are located on the
      pathogenicity locus of C. difficile, a unique characteristic of toxigenic strains
      of this species. Intergenic to the two toxin genes is tcdE, a small 501-bp open
      reading frame of unknown function. Expression of the tcdE gene in Escherichia
      coli caused bacterial cell death. Computational analysis of the amino acid
      sequence of TcdE revealed structural features that are strikingly similar to a
      class of bacteriophage proteins called holins. Holins are cytolytic proteins that
      cause lysis of bacterial hosts to effect the release of progeny phages. Further
      analysis of the recombinant clone expressing TcdE by transmission electron
      microscopy confirmed that the site of action of TcdE is on the bacterial cell
      membrane. The results provide evidence that TcdE is structurally and functionally
      similar to holin proteins. TcdE may function as a lytic protein to facilitate the
      release of TcdA and TcdB to the extracellular environment, as these toxins lack
      signal peptide.

PMID- 11444772
TI  - Distribution of endo-beta-N-acetylglucosaminidase amongst enterococci.
AB  - Enterococci are becoming increasingly important nosocomial pathogens, a fact
      mainly attributed to their antimicrobial resistance profiles. However, the
      enzymic activities required for these organisms to proliferate in vivo have
      received little attention. Enterococcus faecalis has been shown previously to
      produce an endo-beta-N-acetylglucosaminidase activity which cleaves high mannose
      type glycans in glycoproteins between the N-acetylglucosamine residues of the
      pentasaccharide core. This study investigated the distribution of this
      endoglycosidase activity amongst the other enterococcal species. Ribonuclease B,
      a high mannose-type glycoprotein, was used as a substrate and endoglycosidase
      activity was demonstrated by a combination of matrix-assisted laser desorption
      ionisation time-of-flight mass spectrometry and high pH anion-exchange
      chromatography. Endo-beta-N-acetylglucosaminidase activity was present in 10 of
      the 18 enterococcal species isolated from both human and animal sources,
      including all E. faecalis strains. The most notable exception was the lack of
      this activity in all E. faecium isolates tested. All enterococcal species
      possessing endoglycosidase activity utilised the liberated glycans to support
      bacterial growth.

PMID- 11444773
TI  - Lymphocyte recognition of human parvovirus B19 non-structural (NS1) protein:
      associations with occurrence of acute and chronic arthropathy?
AB  - Immune recognition of recombinant parvovirus B19 non-structural (rNS1) protein
      was studied by immunoblot and lymphoproliferative assays in blood from the
      following B19 seropositive groups: B19 infected (n = 14), B19 exposed but non
      infected (n = 16), other illness with rash (n = 3), chronic arthropathy of
      unknown aetiology (n = 4) and healthy controls (n = 7). Sera from 11 B19
      seronegative subjects were also studied. Sera collected at initial diagnosis or
      at the time of accidental B19 exposure in pregnancy were tested for NS1 antibody
      and evidence of B19 DNA by nested PCR. Follow-up specimens were obtained 3-12
      months later for serological, PCR and proliferation studies. B19 DNA was detected
      sporadically in early specimens and in one follow-up specimen from a subject who
      developed chronic arthropathy after B19 infection. There was no correlation with
      development of arthropathy. NS1-specific IgG was detected in early sera from B19
      infected and exposed subjects but to a lesser degree in follow-up specimens, and
      in only one healthy control serum. No correlation with the presence of NS1
      specific antibodies was found with development of acute or chronic arthropathy.
      Although lymphocyte proliferation in response to stimulation with rNS1 in vitro
      occurred at a higher frequency in patients who developed acute and chronic joint
      manifestations after B19 infection, suggesting an association with this outcome,
      NS1-reactive lymphocytes were also found in three B19 seronegative patients, two
      of whom had recently been exposed to B19 but had no illness. Hence, immune
      recognition of NS1 may be more indicative of recent infection with, or exposure
      to, parvovirus B19 than associated with development of arthropathy as previously
      reported.

PMID- 11444774
TI  - Clonal origin of aminoglycoside-resistant Citrobacter freundii isolates in a
      Danish county.
AB  - During 1997, attention was drawn to an increased frequency of aminoglycoside
      resistant Citrobacterfreundii in a Danish county, when a total of 24 resistant C.
      freundii isolates was detected. In this study, 15 such isolates were typed by
      pulsed-field gel electrophoresis, riboprinting and partial sequencing of the gene
      encoding translation initiation factor 2. Fourteen of the 15 isolates were
      identical, as evaluated by their antibiograms and by all these typing methods.
      This epidemic strain harboured the aminoglycoside resistance genes aac(3)-II and
      ant(3")-I, with the latter located in tandem with a dihydrofolate reductase gene
      in a class I integron. The source of the strain remains unresolved.
      Representative isolates were obtained from various specimens from hospitals and
      general practice throughout the county, with no evidence of patient-to-patient
      transmission.

PMID- 11444775
TI  - Clinical importance of extended-spectrum beta-lactamase (PER-1-type)-producing
      Acinetobacter spp. and Pseudomonas aeruginosa strains.
AB  - Recently, an extended-spectrum beta-lactamase (PER-1) was found to be
      disseminated among Acinetobacter spp. and Pseudomonasaeruginosa isolates in
      Turkey. A population-based cohort study was conducted to elucidate predictive
      mortality factors in patients with nosocomial infections caused by Acinetobacter
      spp. and P. aeruginosa, with particular reference to PER-1-type extended-spectrum
      beta-lactamase (ESBL) production. The study group comprised 16 and 21 non
      survivors and 82 and 126 survivors in cohorts infected with Acinetobacter and P.
      aeruginosa, respectively. In the Acinetobacter-infected cohort, nosocomial
      pneumonia, hypotension and infection with a PER-positive isolate were independent
      predictors of mortality. In the P. aeruginosa-infected cohort, impaired
      consciousness, a PER-positive isolate, male sex and (with a negative relative
      risk) urinary tract infection were independent predictors of death. This study
      demonstrated the relationship of PER-1-type ESBL-producing Acinetobacter spp. and
      P. aeruginosa with poor clinical outcome.

PMID- 11444776
TI  - In-vitro antimicrobial activity of four diallyl sulphides occurring naturally in
      garlic and Chinese leek oils.
AB  - The in-vitro antimicrobial activity of garlic oil, Chinese leek oil and four
      diallyl sulphides occurring naturally in these oils against Staphylococcus
      aureus, methicillin-resistant S. aureus (MRSA), three Candida spp. and three
      Aspergillus spp. (total of 276 clinical isolates) was studied. The magnitude of
      activity of the four diallyl sulphides followed the order diallyl tetrasulphide >
      diallyl trisulphide > diallyl disulphide > diallyl monosulphide. These results
      suggest that disulphide bonds are an important factor in determining the
      antimicrobial capabilities of these sulphides. The concentration of four diallyl
      sulphides in garlic and Chinese leek oils was in the range 41.7-52.7% of total
      sulphides. Garlic oil, with a higher concentration of four diallyl sulphides,
      showed greater antimicrobial activity than Chinese leek oil. Diallyl disulphide,
      diallyl trisulphide, diallyl tetrasulphide and the oils rich in these sulphides
      may have a role in the prevention or treatment of infections.

PMID- 11444777
TI  - Genomic identity of pyelonephritogenic Escherichia coli isolated from blood,
      urine and faeces of children with urosepsis.
AB  - Chromosomal genotypes of Escherichia coli isolates from blood, urine and faeces
      of infants with urosepsis were studied to find possible clonality of the
      isolates. The isolates were analysed by PCR for class I, II and III alleles of
      the pyelonephritis-associated adhesin gene papG. The macrorestriction profiles of
      the papG-positive isolates were analysed by pulsed-field gel electrophoresis and
      their O serogroups were determined. Genetically identical E. coli isolates from
      the blood, urine and faeces of the same infant were found in 8 of 10 infants.
      This finding confirmed the results of previous phenotypic studies that the
      reservoir of pyelonephritogenic E. coli is indeed the colon.

PMID- 11444778
TI  - A new method of detection and differentiation of pathogenic from non-pathogenic
      Aspergillus species.

PMID- 11444779
TI  - Production of oxalate in the culture supernate of Burkholderia pseudomallei.

PMID- 11444780
TI  - Shortened gestational age following multifetal pregnancy reduction: can chronic
      placental inflammation be the explanation?
AB  - OBJECTIVE: This study tests the hypothesis that chronic inflammatory foci in the
      placentas of siblings that undergo multifetal pregnancy reduction are associated
      with shortened gestational length. METHODS: Among 446 patients who underwent
      multifetal pregnancy reduction (MPR), 56 delivered at Mount Sinai Hospital, 37
      (66%) had their placentas referred to surgical pathology and 29 (78%) of the 37
      patients had tissue sampled from the placenta of the reduced sibling. Slides were
      reviewed (by C.M.S.) blinded to clinical data. Lesions were diagnosed using
      previously published criteria. Specifically, inflammatory lesions were correlated
      with the various perinatal parameters. Non-parametric testing considered p < 0.05
      to be significant. RESULTS: Ten (35%) of 29 patients had chronic inflammation in
      the reduced placenta. Their gestational age at delivery was 33.1 +/- 3.2 weeks,
      compared to 35.8 +/- 2.3 weeks in those without chronic inflammation (Z = -2.53,
      p = 0.01). There was no difference between the cases with and those without
      chronic inflammation in the reduced placenta, in regard to past reproductive
      history or clinical assessment of the MPR procedure (e.g. the number of attempts,
      duration of the procedure, or post-procedural complications). CONCLUSION: The
      majority of patients who underwent MPR did not develop a chronic inflammatory
      response to the process of 'resorbing' the placental tissues of the reduced
      sibling. However, a significant number (35%) of women who delivered viable
      offspring after MPR had chronic inflammation in the placenta, and had a shortened
      gestational length.

PMID- 11444781
TI  - Reference values of amniotic fluid neuron-specific enolase.
AB  - OBJECTIVE: Enolase is a dimeric cytoplasmic enzyme whose double gamma isoenzyme,
      neuron-specific enolase, is predominantly found in neuronal and neuroendocrine
      tissues. Cell injury causes its release into the blood and cerebrospinal fluid
      (CSF). Neuron-specific enolase has been measured in the serum and CSF of adults
      and full-term asphyxiated neonates as a marker of neurological injury. We
      recently observed an elevation of neuron-specific enolase in the amniotic fluid
      of women whose neonates subsequently developed intraventricular hemorrhage or
      periventricular leukomalacia. The purpose of our study was to establish reference
      values of neuron-specific enolase in the amniotic fluid as a function of
      gestational age. METHODS: A total of 110 amniotic fluid samples, obtained
      primarily for genetic studies (16-20 weeks, n = 22), for evaluation of preterm
      labor (21-35 weeks, n = 66) and for fetal lung maturity studies (36-40 weeks, n =
      22), were analyzed for neuron-specific enolase. Samples were from women who
      subsequently delivered term neonates with normal neurological examinations or who
      delivered preterm neonates with normal neurosonograms up to the 7th day of life.
      Descriptive statistics and non-parametric correlations were used for analysis.
      RESULTS: There was no correlation between gestational age and concentration of
      neuron-specific enolase (Spearman's r = 0.059, p = 0.63). The overall mean neuron
      specific enolase value was 2.5 +/- 1.39 microg/l. The highest value obtained was
      6 microgl. Of the 110 women, 105 (95.5%) had neuron-specific enolase values of
      less than 5 microg/l, while five (4.5%) had values ranging from 5 to 6 microg/l.
      CONCLUSIONS: The amniotic fluid level of neuron-specific enolase does not change
      as a function of gestational age. These stable levels may have utility in the
      evaluation of cases with fetal neurological injury.

PMID- 11444782
TI  - Prospective comparison of the startle test (recoil) and non-stress test.
AB  - OBJECTIVE: Our purpose was to compare fetal heart rate reaction to external
      physical stimulation with the non-stress test (NST). METHODS: This was a
      prospective study evaluating documentation of fetal heart accelerations by two
      methods. The standard NST was performed prior to the ultrasound evaluation. The
      NST results were not available to the ultrasonographer. M-mode ultrasound was
      used to establish a stable fetal heart rate. The ultrasound transducer was used
      to stimulate fetal movement by indentations of the uterus over the fetal small
      parts. A second fetal heart rate was determined within 15 s after stimulation.
      RESULTS: A total of 122 patients had 159 studies performed. The fetal heart rate
      range due to fetal startle (recoil) was -22 to 14 (median of 3) in the 45 fetuses
      with non-reactive NSTs and 1 to 38 (median of 15) in the 114 fetuses with a
      reactive NST (p <0.001). A receiver operating curve comparing the fetal response
      to the startle and the NST revealed an area under the curve of 0.972, consistent
      with high specificity and sensitivity. CONCLUSION: The fetal heart rate response
      to external stimulation correlates with the formal NST.

PMID- 11444783
TI  - Mandated preterm delivery: its prevalence and impact at a tertiary referral
      center.
AB  - OBJECTIVE: To determine the prevalence and impact of mandated preterm deliveries
      at a tertiary referral center. METHODS: A chart review was conducted at our
      institution on all livebirths from 24 weeks to completion of 37 weeks' gestation
      between 1 January 1998 and 31 December 1999. Mandated delivery was defined as
      intentional intervention because of a deteriorating maternal or fetal condition.
      Reasons for intervention and intrapartum courses were compared with two other
      preterm groups (premature ruptured membranes, spontaneous labor) delivering
      during the same period. Statistical analyses included the Student t test,
      univariate ANOVA, X2 test and Mann-Whitney test. RESULTS: A total of 894
      pregnancies delivered preterm, with 132 (14.8%) being mandated. Primary reasons
      for mandated delivery included severe pre-eclampsia (69.0%), vaginal bleeding
      (11.4%), deteriorating maternal illness (10.6%), worsening fetal growth
      restriction (6.1%) or major fetal malformation (3.0%). Delivery at less than 34
      weeks was more common in the mandated group (68.9%) than in the ruptured
      membranes group (41.2%, p < 0.005) or in the spontaneous labor group (46.5%; p <
      0.01). Cesarean section rates were higher in the mandated group (69.7%) than in
      the ruptured membranes group (18.3%; p <0.001) or in the spontaneous labor group
      (21.5%; p < 0.001). The presence of an unfavorable cervix, unsuccessful trial of
      labor, non-cephalic fetal presentation, or fetal intolerance of labor explained
      the high rate of surgery. CONCLUSIONS: Conditions mandating delivery accounted
      for 14.8% of all preterm births. Mandated delivery is associated with a greater
      need for delivery before 34 weeks, often by Cesarean section.

PMID- 11444784
TI  - Cigarette smoking and pre-eclampsia: their association and effects on clinical
      outcomes.
AB  - OBJECTIVE: To determine the effects of smoking on pre-eclampsia in an inner-city,
      predominantly African-American prenatal population. METHODS: We performed a
      retrospective cohort study of all primigravidas who delivered singletons in our
      institution between 1980 and 1989. The study population consisted of 1862 smokers
      and 16,508 non-smokers. Univariate analysis and multiple logistic regression were
      used to identify relationships between smoking and adverse outcomes. RESULTS: The
      pre-eclampsia rate was significantly lower among smokers (11.3% vs. 13.0%, OR
      0.85, 95% CI 0.73-0.99). Smokers with pre-eclampsia had higher rates of infants
      with low birth weight (OR 1.44, 95% CI 1.26-1.65) and very low birth weight (OR
      1.85, 95% Cl 1.55-2.20) and higher rates of placental abruption (OR 3.49, 95% CI
      1.65-7.28) compared to non-smoking pre-eclamptics. This relationship persisted
      after correction for age, race, chronic hypertension and pre-eclampsia as
      confounding variables. CONCLUSIONS: Cigarette smoking was associated with a lower
      rate of pre-eclampsia among primigravidas independently of other maternal
      factors. Perinatal outcomes were significantly worsened among pre-eclamptics who
      smoked.

PMID- 11444785
TI  - Vaginal birth of twins after a previous Cesarean section.
AB  - OBJECTIVE: To determine whether a vaginal birth of twins after a Cesarean section
      carried greater risk than for a singleton gestation as well as determining
      whether there was a similar likelihood of successful vaginal birth. METHODS: A
      retrospective study was carried out of all twin pregnancies in which vaginal
      birth was attempted after a Cesarean section, in 1991-99. The next three
      consecutive singleton pregnancies in which vaginal birth was attempted after a
      Cesarean section were also evaluated. Comparisons were made for successful
      vaginal birth after Cesarean section complications (blood loss, uterine rupture
      or dehiscence, hysterectomy, chorioamnionitis and neonatal morbidity). Where
      appropriate, X2 tests of association or Student's t tests were used. Significance
      was set at p < 0.05. RESULTS: A total of 19 twin pregnancies met the study
      criteria. There were 57 controls. Gestational ages differed slightly (twin
      pregnancies, 36.3 weeks; controls, 39.3 weeks). The success rate of vaginal birth
      after Cesarean section was 84.2% for twin pregnancies and 75.4% for controls. The
      incidence of postpartum hemorrhage was 5.3% for both groups. One uterine rupture
      occurred in the control group; none occurred in the twin pregnancy group. One
      uterine dehiscence occurred in each group. No significant differences were found
      for any of the other parameters tested. CONCLUSION: The option of vaginal birth
      of twins after Cesarean section appears to have a similar risk and shares a
      similar likelihood of success to those of a singleton pregnancy. In view of the
      lack of increased complications, this option can be offered to patients with twin
      pregnancies who are eligible for vaginal birth after Cesarean section.

PMID- 11444786
TI  - Etiology and outcome of hydrops fetalis.
AB  - OBJECTIVES: To identify the etiology and pregnancy outcome of hydrops fetalis in
      a cohort of pregnancies referred to a tertiary maternal fetal medicine center in
      the UK. These data allow the review of a large series of pregnancies affected by
      hydrops fetalis and emphasize the importance of investigation and then treatment
      of individual cases. This provides parents with improved information and
      especially specific prognostic information. METHODS: A retrospective review of 63
      consecutive cases of hydrops fetalis managed between September 1996 and March
      1999. RESULTS: Of the pregnancies, 12.7% (n = 8) were associated with an 'immune'
      etiology. Of these, 62.5% (n = 5) had fetal anemia due to anti-D, 25% (n = 2)
      anti-Kell and 12.5% (n = 1) anti-c antibodies. The remaining 55 cases (87.3%) had
      a non-immune cause. Eight (14.5%) were due to human parvovirus B19 infection.
      Fourteen cases (25.5%) were associated with aneuploidy and, in four (7.3%), a
      primary hydrothorax was the cause of the non-immune hydrops fetalis. A cardiac
      cause was found in five (9.1%) cases. Three of these had supraventricular
      tachycardia and one had congenital complete heart block. Cystic hygroma was
      associated with hydrops fetalis in six cases. Twin-twin transfusion syndrome was
      the cause for hydrops in two cases. Massive transplacental hemorrhage was
      identified in one case. Fetal akinesia and muscular dystrophy caused hydrops in
      one case each. In 14.5% (8/55) of cases no obvious cause was identified and these
      were classified as 'idiopathic'. Three other cases could not be classified
      because parents declined investigations (unclassified). In the pregnancies with
      non-immune hydrops fetalis, the outcome was favorable in 27.3% (15/55) of cases.
      CONCLUSION: The prognosis of hydrops fetalis differs markedly between different
      etiological groups. Etiologies range from treatable causes with a good outcome
      and probably no long-term side-effects (as in case of parvovirus B19), to others
      which are incompatible with life or are associated with considerable perinatal
      morbidity and mortality.

PMID- 11444787
TI  - Oxidant damage to DNA and pregnancy outcome.
AB  - OBJECTIVE: DNA is susceptible to oxidation and is constantly being damaged and
      repaired in living cells. The most abundant of the nucleoside oxidation products
      is 8-oxo-7,8 dihydro-2 deoxyguanosine (8 OH-dG). Our objective was to determine
      whether oxidative damage to DNA, as measured by 8 OH-dG, is increased with poor
      pregnancy outcome. METHOD: We utilized a case-control design to study oxidative
      damage to DNA during an ongoing prospective study. Cases (n = 18) included all
      women giving birth to a low-birth-weight (< 2500 g) or growth-restricted (< 10th
      centile) or preterm infant (< 37 completed weeks). Controls (n = 34) were
      selected at random from women with normal pregnancies. Urine samples were
      obtained early in the third trimester (28 +/- 2 weeks) and normalized to
      creatinine. Diet was assessed at three points during pregnancy. RESULTS: Cases
      had significant (p < 0.05) increases in maternal urinary 8 OH-dG excretion at
      week 28, when all cases were considered and when cases were defined as those who
      delivered a low-birth-weight infant. 8OH-dG excretion, in turn, correlated
      positively with saturated fat in the maternal diet. CONCLUSION: This study
      suggests that gravidas with poor pregnancy outcome have increased oxidative
      damage to their DNA early in the third trimester of pregnancy.

PMID- 11444788
TI  - A comparison of intermittent vaginal administration of two different doses of
      misoprostol suppositories with continuous dinoprostone for cervical ripening and
      labor induction.
AB  - PURPOSE: To compare the efficacy of a vaginal insert administering continuous
      dinoprostone with vaginal suppositories containing two different doses of
      misoprostol for cervical ripening and induction of labor. STUDY DESIGN: In this
      prospective, randomized, double-blinded study, 118 patients with indications for
      induction of labor and an unfavorable Bishop score were randomly assigned to
      receive either continuous dinoprostone, misoprostol 35-microg suppositories, or
      misoprostol 50-microg suppositories. RESULTS: No significant differences were
      noted among the three groups in the change of Bishop score, induction of active
      labor or the time from initial treatment to delivery. Active labor occurred in
      roughly two-thirds of the patients in an average of about 5.7-6.7 h regardless of
      treatment assignment. When the two misoprostol groups were combined, a shorter
      interval from insertion to vaginal delivery was observed in the nulliparous women
      receiving misoprostol than those receiving continuous dinoprostone (21.3 vs. 27.2
      h, p = 0.019). Except for the significantly lower incidence of tachysystole
      observed in the combined misoprostol group (3.8% vs. 15.4%, p = 0.036), there
      were no other significant differences between the groups in mode of delivery or
      in adverse maternal, fetal, or neonatal effects. CONCLUSION: Misoprostol
      suppositories appeared to be as effective and safe as continuous dinoprostone in
      inducing cervical ripening in this sample.

PMID- 11444789
TI  - Sequential use of Prepidil and extra-amniotic saline infusion for the induction
      of labor in nulliparous women with very low Bishop scores.
AB  - OBJECTIVE: To evaluate the efficacy of sequential use of Prepidil (prostaglandin
      E2 gel) and extra-amniotic saline infusion for the induction of labor in
      nulliparous women with very low Bishop scores. STUDY DESIGN: Nulliparous women
      with singleton gestations, intact membranes and a cervical Bishop score of < or =
      2 who received Prepidil gel and extra-amniotic saline infusion sequentially for
      the induction of labor between July 1996 and July 1998 were studied. RESULTS:
      Thirty-one women met the inclusion criteria. Indications for induction included
      post-dates (six of 31), pre-eclampsia (ten of 31), diabetes (three of 31),
      oligohydramnios (three of 31), intrauterine growth restriction (two of 31) and
      non-reactive non-stress test (NST) (seven of 31). The average time from onset of
      induction to delivery was 38.1 +/- 13.5 h. Vaginal delivery was achieved in
      80.6%. Women requiring > 2 doses of Prepidil had a higher risk of delivering
      abdominally (OR = 3.5). Three of seven (42.9%) women with labor induced for non
      reactive NST but only three of 24 (12.5%) with labor induced for other
      indications had a Cesarean section delivery (p < 0.001). CONCLUSIONS: Nulliparous
      women with very unfavorable cervices can be counselled that they have an 80%
      chance of vaginal delivery using sequential Prepidil and extra-amniotic saline
      infusion as an induction method, with 90% delivering within the first 48 h.

PMID- 11444790
TI  - Plasma progesterone, dehydroepiandrosterone sulfate and estriol levels during
      labor induction with a sustained-release prostaglandin E2 vaginal insert.
AB  - OBJECTIVE: To measure plasma progesterone, dehydroepiandrosterone sulfate (DHEAS)
      and estriol levels in women induced for labor with a sustained-release vaginal
      polymer prostaglandin E2 insert, and to analyze the relationships between the
      changes in hormone levels and Bishop score. METHODS: Twelve primipara and 12
      multipara were treated with a sustained-release polymer vaginal prostaglandin E2
      insert (0.3 mg/h) for up to 24 h. The Bishop score was assessed at the start and
      end of therapy, and serum samples were collected at 4-h intervals. Plasma levels
      of progesterone, DHEAS and estriol were measured by specific radioimmunoassays.
      RESULTS: Exposure averaged 13.5 +/- 7.2 h. Progesterone levels decreased in the
      majority of patients (79.2%) after the start of therapy. Higher baseline DHEAS
      and estriol levels were observed among women who achieved an improvement in
      Bishop score of at least 4 during prostaglandin E2 treatment. CONCLUSIONS: Higher
      DHEAS and estriol levels prior to labor induction with prostaglandin E2 may be
      indicators of a favorable labor outcome. Additional studies are needed to
      substantiate the decrease in progesterone levels observed in this study and the
      importance of this phenomenon for the mechanism of labor induction with
      prostaglandin E2.

PMID- 11444791
TI  - Evaluation of a rapid optical immunoassay-based test for group B streptococcus
      colonization in intrapartum patients.
AB  - OBJECTIVE: To compare an optical immunoassay (OIA) rapid diagnostic kit to
      standard culture for the diagnosis of vaginal colonization with group B
      streptococcus (GBS) and to assess the accuracy and reproducibility of the OIA
      results. METHOD: A total of 301 patients in labor were prospectively evaluated
      for GBS colonization with a test approved by the Food and Drug Administration
      (STREP B OIA kit, Biostar, Boulder, CO, USA) and by culture. The vagina was
      simultaneously sampled with two swabs. Rectal culture was obtained separately.
      RESULTS: By the criterion of a positive culture, the vagina was colonized by GBS
      in 33 of 301 (11%) patients; and the rectum in 42 of 301 (13.9%). The vagina or
      rectum or both were colonized by CBS in 54 of 301 (17.9%) of patients. The OIA
      had sensitivity, specificity, positive predictive value and negative predictive
      value of 63.6%, 86.3%, 37.5% and 94.8%, respectively. The OIA had a kappa
      statistic score of 0.59. CONCLUSION: The OIA is not an adequately sensitive rapid
      kit for reliable detection of GBS colonization of the vagina. The results of the
      OIA were only moderately accurate and reproducible.

PMID- 11444792
TI  - A comparison of four techniques for measuring central adiposity in postpartum
      adolescents.
AB  - OBJECTIVE: To develop a reliable office technique for measuring central body fat
      in postpartum adolescents, we compared: first, a direct sonographic measurement
      of visceral adiposity to measurements of visceral and subcutaneous abdominal
      adiposity by computed tomography (CT); and second, skinfold caliper and
      sonographic measurements of subcutaneous adipose tissue distribution to CT
      measurements of visceral and subcutaneous abdominal adiposity. METHODS:
      Postpartum adipose tissue distribution was assessed in 15 teenagers by measuring
      the thickness of the subcutaneous fat at six body sites with skinfold calipers
      and ultrasound. Visceral adiposity was measured directly by ultrasound and CT.
      Taking the CT measurements as the standards, Pearson correlations and regression
      analyses were used to compare ultrasound measurement of visceral adiposity and
      the skinfold caliper and sonographic measurements of subcutaneous adipose tissue
      distribution. RESULTS: All of the adiposity measurements correlated significantly
      with the two CT measurements. The correlations between the ultrasound and the two
      CT measurements of abdominal adiposity were weaker than the correlations between
      the skinfold caliper and the sonographic determinations of subcutaneous adiposity
      and the two CT measurements of abdominal adiposity. Multivariate analyses
      identified the sonographic determination of subcutaneous adiposity at the costal
      site as the best independent predictor of central adiposity. CONCLUSIONS: The
      results of this study do not support the validity of ultrasound measurement of
      visceral adiposity as a measure of central adiposity in postpartum teenagers, but
      do suggest that sonographic determinations of subcutaneous adiposity could be
      useful for conducting epidemiological studies of the metabolic sequelae of
      gestational weight gain in this high-risk population of young women.

PMID- 11444793
TI  - Primary hyperparathyroidism and acute pancreatitis during the third trimester of
      pregnancy.
AB  - The simultaneous occurrence of maternal primary hyperparathyroidism (PHPT) and
      acute pancreatitis during pregnancy is very rare. We report a case of concurrent
      PHPT and pancreatitis during the third trimester of pregnancy. A summary of the
      relevant literature regarding the clinical course and recommended management in
      relation to this case is also presented.

PMID- 11444794
TI  - Experimenting on the past: the enigma of von Economo's encephalitis lethargica.
AB  - Encephalitis lethargica (EL) was a complex and mysterious disease that appeared
      around the same time as the great influenza pandemic of 1918. The contemporaneous
      relationship of the 2 diseases led to speculation that they were causally
      related. Contemporary and subsequent observers conjectured that the influenza
      virus, directly responsible for the deaths of more than 20 million people, might
      also have been the cause of EL. A review of the extensive literature by observers
      of the EL epidemic suggests that most contemporary clinicians, epidemiologists,
      and pathologists rejected the theory that the 1918 influenza virus was directly
      responsible for EL. Disappearance of the acute form of EL during the 1920s has
      precluded direct study of this entity. However, modern molecular biology
      techniques have made it possible to examine archival tissue samples from victims
      of the 1918 pandemic in order to detect and study the genetic structure of the
      killer virus. Similarly, tissue samples from EL victims can now be examined for
      evidence of infection by the 1918 influenza virus.

PMID- 11444795
TI  - Tracing axons in the peripheral nerve using lacZ gene recombinant adenovirus and
      its application to regeneration of the peripheral nerve.
AB  - The usefulness of recombinant adenovirus with LacZ to trace axons in the
      peripheral nervous system was investigated. Recombinant adenovirus with LacZ was
      applied to the cut end of the tibial nerve in rats. The LacZ gene product (B
      galactosidase) filled axons of the tibial nerve, which permitted the continuous
      long-range tracing of axons. Further, the branching and the direction of the
      branches could also be examined. Labeled axons in the tibial nerves ran parallel
      to each other without branching and kept this relative position in the tibial and
      the sciatic nerve. When the virus was introduced to the regenerating nerve using
      a silicon tube, the regenerating fibers grew tortuously with short branches in
      the bulge at the proximal end of the silicon tube. The fibers grew straight in
      the tube and passed through the bulge at the distal end of the tube without
      branching. These observations indicate that the LacZ gene recombinant adenovirus
      is a useful tracer for the study of the peripheral nervous system and of the
      regeneration processes.

PMID- 11444796
TI  - Bone marrow chimeric rats reveal the unique distribution of resident and
      recruited macrophages in the contused rat spinal cord.
AB  - Brain and spinal cord inflammation that develops after traumatic injury is
      believed to differentially influence the structural and/or physiological
      integrity of surviving neurons and glia. It is possible that the functional
      dichotomy of CNS inflammation results from the activity of a heterogeneous
      macrophage population elicited by trauma. Indeed, unique functions have been
      attributed to macrophages derived from resident microglia versus those
      originating from infiltrating monocytes. Thus, whether progressive tissue injury
      or repair is favored could be explained by the disproportionate contributions of
      one macrophage subset relative to the other. Descriptive neuroanatomical studies
      are a reasonable first approach to revealing a relationship between microglia,
      recruited blood monocytes/macrophages, and regions of tissue degeneration and/or
      repair. Unfortunately, it is not possible to differentiate between CNS macrophage
      subsets using conventional immunohistochemical approaches. In the present study,
      we have used radiation bone marrow chimeric rats to definitively characterize the
      macrophage reaction elicited by experimental spinal contusion injury. In chimeric
      animals, antibodies raised against unique cell surface molecules expressed on
      bone marrow-derived cells (BMCs) were used to distinguish infiltrating BMCs from
      resident microglial-derived macrophages. Our findings indicate that the onset and
      plateau of macrophage activation (previously shown to be 3 and 7 days postinjury,
      respectively) is dominated initially by microglial-derived macrophages and then
      is supplanted by hematogenous cells. While resident macrophages are ubiquitously
      distributed throughout the injury site, leukocyte-derived monocytes exclusively
      infiltrate the gray matter and to a lesser extent subpial white matter.
      Generally, monocyte foci in white matter remain associated with the lumen or
      abluminal surface of blood vessels, i.e. few cells actually infiltrate the
      parenchyma. If functional differences exist between CNS macrophage subsets,
      differences in the time-dependent accumulation and distribution of these cell
      types could differentially influence the survival of surrounding neurons and
      glia.

PMID- 11444797
TI  - Expression and activities of aldo-keto oxidoreductases in Alzheimer disease.
AB  - A reactive intermediate generated by lipid peroxidation, 4-hydroxy-2-nonenal
      (HNE), has received considerable attention as a potential effector of oxidative
      damage and Abeta peptide-mediated neurotoxicity in Alzheimer disease (AD).
      However, little is known about aldo-keto oxidoreductases, a group of enzymes that
      constitute a major detoxifying pathway for HNE and related reactive aldehydes in
      human brain. We have determined the regional, cellular, and class distribution in
      human brain of the 4 major aldo-keto oxidoreductases that detoxify HNE: aldehyde
      dehydrogenase (ALDH): aldose reductase; aldehyde reductase: and alcohol
      dehydrogenase (ADH). Of these 4 enzymes, only ALDH and aldose reductase were
      expressed in cerebral cortex. hippocampus, basal ganglia, and midbrain: all 4
      enzymes were present in cerebellum. In cerebrum and hippocampus, aldose reductase
      was localized to pyramidal neurons and mitochondrial class 2 ALDH was localized
      to glia and senile plaques. ALDH, but not aldose reductase, activity was
      significantly increased in temporal cortex from patients with AD compared to age
      matched controls. These results suggest that in brain regions involved in AD,
      neurons and glia utilize different mechanisms to detoxify HNE, and that increased
      ALDH activity is a protective response of cerebral cortex to AD.

PMID- 11444798
TI  - Influenza RNA not detected in archival brain tissues from acute encephalitis
      lethargica cases or in postencephalitic Parkinson cases.
AB  - Encephalitis lethargica (EL) was a mysterious epidemic. temporally associated
      with the 1918 Spanish influenza pandemic. Numerous symptoms characterized this
      disease, including headache, diplopia, fever, fatal coma, delirium, oculogyric
      crisis, lethargy, catatonia, and psychiatric symptoms. Many patients who
      initially recovered subsequently developed profound, chronic parkinsonism. The
      etiologic association of influenza with EL is controversial. Five acute EL
      autopsies and more than 70 postencephalitic parkinsonian autopsies were available
      in the Armed Forces Institute of Pathology (AFIP) tissue repository. Two of these
      5 acute EL cases had histopathologic changes consistent with that diagnosis. The
      remaining 3 cases were classified as possible acute EL cases as the autopsy
      material was insufficient for detailed histopathologic examination. RNA lysates
      were prepared from 29 CNS autopsy tissue blocks from the 5 acute cases and 9
      lysates from blocks containing substantia nigra from 2 postencephalitic cases.
      RNA recovery was assessed by amplification of beta-2-microglobulin mRNA and 65%
      of the tissue blocks contained amplifiable RNA. Reverse transcription-polymerase
      chain reaction (RT-PCR) for influenza matrix and nucleoprotein genes was negative
      in all cases. Thus, it is unlikely that the 1918 influenza virus was neurotropic
      and directly responsible for the outbreak of EL.

PMID- 11444799
TI  - Autometallographic tracing of bismuth in human brain autopsies.
AB  - For decades, drugs containing bismuth have been used to treat gastrointestinal
      disorders. Although a variety of adverse effects, including neurological
      syndromes, have been recorded, the biological/toxicological effects of bismuth
      ions are far from disclosed. Until recently, only quantitative assessments were
      possible, but resent research has made histochemical tracing of bismuth possible.
      The technique involves silver enhancement of bismuth crystallites by
      autometallography (AMG). In the present study, the localization of bismuth was
      traced by AMG in sections of paraffin-embedded brain tissue obtained by autopsy
      from 6 patients suffering from bismuth intoxication in a period ranging from 1975
      through 1977. Tissue was analyzed at light and electron microscopical levels, and
      the presence of bismuth further confirmed by proton-induced x-ray emission
      (PIXE). Clinical data and bismuth concentrations in blood, cerebellum, and
      thalamus were measured by atomic absorption spectrophotometry (AAS) and are
      reported here. Histochemical analyses demonstrate that bismuth accumulated in
      neurons and glia cells in the brain regions examined (neocortex, cerebellum,
      thalamus, hippocampus). Cerebellar blood vessels stained most intensely. The PIXE
      and AAS data correlated with the histochemical staining patterns and intensities.
      At the ultrastructural level, bismuth was found to accumulate intracellularly in
      lysosomes and extracellularly in the basement membranes of some vessels.

PMID- 11444800
TI  - Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and
      its regulatory cyclins A and B.
AB  - Tuberous sclerosis (TSC) is a multi-system disorder characterized by
      hamartomatous tumors and abnormal brain development, with multiple foci of
      disrupted neuronal migration and giant dysmorphic neurons within cortical tubers.
      TSC is associated with mutations in 2 genes, TSC1 and TSC2, which encode hamartin
      and tuberin, respectively. The functions of these proteins have yet to be
      determined. Recently, the Drosophila homologue of TSC2, gigas, has been shown to
      be required for the G2/M transition of the cell cycle. However, the mechanism of
      this action remains unknown. Because the cyclin-dependent kinase CDK1 forms a
      complex with cyclin B1 to trigger the G2/M transition, we hypothesized that
      tuberin interacts with CDK1 to regulate its activity. In the study reported in
      this paper, we have used co-immunoprecipitation and confocal microscopy to
      demonstrate that tuberin interacts with and co-localizes with CDK1 and its
      binding partner cyclin B1 in multiple cell types. We also demonstrate that
      hamartin interacts with CDK1 and cyclin B1. We further present evidence that
      tuberin interacts with the other regulatory subunit of CDK1, cyclin A. These
      findings suggest a direct role for tuberin and hamartin in modulating the
      activity of CDK1 during G2 and the G2/M transition. This is the first description
      of a role for both tuberin and hamartin in a common cellular function, providing
      a potential mechanism for the identical clinicopathologic manifestations that
      result when either of these proteins are inactivated.

PMID- 11444801
TI  - Mice with mutations in the mahogany gene Atrn have cerebral spongiform changes.
AB  - A new mutation characterized by mahogany coat color, sprawling gait, tremors, and
      severe vacuolization of cerebrum, brainstem, granular layer of cerebellum and
      spinal cord was discovered in a stock of Mus castaneus mice. Tests for allelism
      using mice homozygous for 2 known mahogany attractin (Atrnmg) mutants showed that
      the new mutation was an allele of Atrnmg. Northern analysis showed no expression
      of Atrn in the new mutants. Southern analysis strongly suggested that the new
      mutation deleted most of the Atrn gene, but was not large enough to affect
      flanking genes including the prion gene, Prnp, located 1.1 cM from Atrn on
      Chromosome 2. Histopathological analysis of brains from each of the 2 known
      Atrnmg mutants showed that they also have severe spongiform changes. This finding
      was surprising and raises questions about the mechanism by which mahogany
      controls appetite and metabolic rate, as recently reported.

PMID- 11444802
TI  - Alzheimer beta amyloid deposition enhanced by apoE epsilon4 gene precedes
      neurofibrillary pathology in the frontal association cortex of nondemented senior
      subjects.
AB  - To clarify how Alzheimer disease pathology develops in the brains of nondemented
      subjects, we examined the interrelations among the amounts and morphology of
      Abeta deposition, neurofibrillary pathology, and apolipoprotein E (ApoE) genotype
      in the frontal association cortex of 101 autopsy brains from patients aged
      between 40 to 83. Senile plaque density correlated well with the logarithmic data
      of insoluble Abeta measured by enzyme immunoassay (EIA). The amounts of Abeta42
      ETA increased dramatically in the late preclinical stage, whereas the AP42+
      plaque density increased in the early preclinical stage. Neurofibrillary
      pathology appeared only in the areas with severe Abeta deposition and in subjects
      aged over 70. The ApoE epsilon4 allele enhanced the Abeta3 deposition in
      presenile subjects. Plaque-associated glial Abeta was prominent in subjects with
      mild to moderate Abeta deposition. The morphology of cerebral Abeta deposition
      changed from diffuse plaques with small amounts of Abeta in each plaque in the
      early preclinical stage to primitive/neuritic plaques with larger amounts of
      Abeta in each plaque in the late preclinical stage. Our findings suggest that the
      prevention of Abeta deposition in the late preclinical stage can be a rational
      therapeutic target, especially in elderly people with ApoE epsilon4 allele.

PMID- 11444803
TI  - Use of surface plasmon resonance for real-time measurements of the global
      conformational transition in human phenylalanine hydroxylase in response to
      substrate binding and catalytic activation.
AB  - In the present study the optical biosensor technique, based on the surface
      plasmon resonance (SPR) phenomenon, was used for real-time measurements of the
      reversible binding of the pterin cofactor (6R)-l-erythro-5,6,7,8
      tetrahydrobiopterin (BH(4)) and l-phenylalanine (l-Phe) to human phenylalanine
      hydroxylase (hPAH). When BH(4) (241 Da) was injected over the sensor chip with
      immobilized tetrameric wt-hPAH a positive DeltaRU response was observed with a
      square-wave type of sensorgram and a saturable response (about 25 RU/(pmol
      subunit/mm(2)) with a [S](0.5) value of 5.6 +/- 0.8 microM for the pterin
      cofactor. The rapid on-and-off rates were, however, not possible to determine. By
      contrast, when l-Phe (165 Da) was injected a time-dependent increase in RU (up to
      about 3 min) and a much higher saturable DeltaRU response (about 75 RU/(pmol
      subunit/mm(2)) at 2 mM l-Phe) than expected (i.e., <5 RU/(pmol subunit/mm(2)))
      from the low molecular mass of l-Phe were observed in the sensorgram. The half
      time for the on-and-off rates were 6 +/- 2 and 9 +/- 1 s, respectively, at 2 mM l
      Phe. The steady-state (apparent equilibrium) response revealed a hyperbolic
      concentration dependence with a [S](0.5) value of 98 +/- 7 microM. The [S](0.5)
      values of both pterin cofactor and l-Phe were lower than those determined by
      steady-state enzyme kinetic analysis. Evidence is presented that the DeltaRU
      response to l-Phe is accounted for by the global conformational transition which
      occurs in the enzyme upon l-Phe binding, i.e., by the slow reversible transition
      from a low activity state ("T"-state) to a high activity state ("R"-state)
      characteristic of this hysteretic enzyme.

PMID- 11444804
TI  - A disposable optrode using immobilized tyrosinase films.
AB  - A disposable fiber-optic sensor based on the immobilized tyrosinase enzyme in a
      composite biopolymer and its application for the detection of 3,4
      dihydroxyphenyalanine (L-dopa) and its analog are described. The enzymatic
      oxidation product of L-dopa was stabilized through formation of an adduct with 3
      methyl-2-benzothiazoline hydrazone resulting in enhanced accuracy and sensitivity
      of the measurements. The response was found to be linear and concentration
      dependent in the range of 5 x 10(-5) to 4 x 10(-4) M (r(2) = 0.9307) for the
      substrate l-dopa over the pH range 5.8 to 7.2 with response times of 8 min. The
      immobilized enzyme films are stable for 4 months when stored under moisture-free
      conditions at 4 degrees C.

PMID- 11444805
TI  - External surface display of proteins linked to DNA-binding domains.
AB  - A novel system (DBDX) was developed which allows the external surface display on
      filamentous bacteriophage of proteins fused to either the N- or the C-terminus of
      a DNA-binding protein. In conjunction with helper phage infection, expression of
      proteins fused to the estrogen receptor DNA-binding domain (DBD) in a phagemid
      vector containing the DNA sequence recognized by the DBD resulted in the
      production of phage particles which display the fusion protein through the phage
      pVIII coat on the external surface of the particle. The viability of the
      technique was established with several model systems: particles displaying the C
      terminal domain of N-cadherin or the biotinylation domain of propionyl coenzyme A
      carboxylase fused to the C-terminus of the DBD were found to be bound
      specifically by antibody or streptavidin, respectively. Human kappa constant
      region cDNA was selected from a N-terminal DBD fusion lymphocyte cDNA library
      after two rounds of selection with anti-kappa antibody. This display system may
      complement currently available bacterial selection techniques.

PMID- 11444806
TI  - Fluorescence lifetime characterization of novel low-pH probes.
AB  - The structures and functions of the cellular acidic compartments are strongly
      dependent on the pH gradients across vesicular membranes. Measurement and imaging
      of the vesicular pH require fluorophores with appropriate pK(a) values. In this
      report, we characterized the pH-dependent lifetime responses of a family of
      acidotropic probes, LysoSensors, to evaluate their usefulness to low-pH lifetime
      imaging. LysoSensors are cell-permeable weak bases that selectively accumulate in
      acidic vesicles after being protonated. They have higher quantum yields at lower
      pH ranges to allow visualization of the lysosomes. For LysoSensors DND-167, DND
      189, and DND-153, raising the buffer pH increased the quenching effects of their
      basic side chains and substantially reduced their steady-state fluorescence and
      lifetimes. The apparent pK(a) values determined from their lifetime responses
      were shifted to near neutral values because of the dominant intensity
      contribution from their protonated species. One unique property of LysoSensor DND
      189 is its nonmonotonic lifetime responses of the maxima occurring between pH 4
      and 5. LysoSensor DND-192 did not show significant lifetime changes over a wide
      pH range. LysoSensor DND-160, which was the only excitation and emission
      ratiometric probe, showed significant pH-dependent lifetime changes as well as
      its spectral shifts. Its apparent pK(a) values determined from the lifetime
      responses were comparable to the lysosomal pH because of its bright basic form.
      Because of the pH-dependent absorption spectra, the apparent pK(a) values could
      be manipulated between 3 and 5 by changing the excitation and/or emission
      wavelengths. These results indicate that LysoSensor DND-160 is a promising probe
      for lifetime imaging to determine lysosomal pH.

PMID- 11444807
TI  - Aptamer beacons for the direct detection of proteins.
AB  - We have designed a new class of molecules, which we term aptamer beacons, for
      detecting a wide range of ligands. Similar to molecular beacons, aptamer beacons
      can adopt two or more conformations, one of which allows ligand binding. A
      fluorescence-quenching pair is used to report changes in conformation induced by
      ligand binding. An anti-thrombin aptamer was engineered into an aptamer beacon by
      adding nucleotides to the 5'-end which are complementary to nucleotides at the 3'
      end of the aptamer. In the absence of thrombin, the added nucleotides will form a
      duplex with the 3'-end, forcing the aptamer beacon into a stem-loop structure. In
      the presence of thrombin, the aptamer beacon forms the ligand-binding structure.
      This conformational change causes a change in the distance between a fluorophore
      attached to the 5'-end and a quencher attached to the 3'-end. Aptamer beacon can
      be a sensitive tool for detecting proteins and other chemical compounds.

PMID- 11444808
TI  - Using epitope-aequorin conjugate recognition in immunoassays for complex
      proteins.
AB  - Recombinant techniques are used to fuse biologically important molecules or
      peptides to the N-terminus of the photoprotein aequorin such that the binding
      characteristics of the molecule and the bioluminescent activity of aequorin are
      retained. This work demonstrates that the peptide region of a bulky protein can
      be used to develop an assay for the protein. A heterogeneous competitive binding
      assay was first developed for HPC4 epitope, the binding region of protein C,
      using HPC4-apoaequorin conjugate. It was observed that the binding of HPC4
      epitope to its monoclonal antibody and the bioluminescence properties of aequorin
      were retained in the fusion protein. The same strategy and the same fusion
      protein were used to develop the assay for protein C. This project could
      potentially be a model for large biomolecules utilizing only the binding region
      of the protein in the labeled analyte. Also, this assay can be used in clinical
      diagnostics for the quantitative detection of protein C.

PMID- 11444809
TI  - Individual mitochondrion characterization: a comparison of classical assays to
      capillary electrophoresis with laser-induced fluorescence detection.
AB  - A method has been developed that uses capillary electrophoresis (CE) with laser
      induced fluorescence detection (LIF) for measuring protein abundance in
      individual mitochondria collected from a discontinuous density gradient and
      labeled with Mitotracker Green. From these measurements we determined the
      distribution of protein content per mitochondrion and the relative abundance of
      mitochondrial proteins in density gradient fractions. In addition, this method is
      useful for counting mitochondria and, as a consequence, determining the number of
      mitochondria per unit volume or estimate mitochondria copy number per cell. It
      was determined that mitochondria accumulate in two interfaces defined by
      consecutive layers of 35% Metrizamide, 17% Metrizamide, and 6% Percoll. The
      presence of mitochondria in these interfaces was also confirmed using a modified
      Lowry assay that prevents interference from Metrizamide and Percoll and
      determines total protein content, and a succinate dehydrogenase assay that uses
      dichloroindophenol as an electron acceptor and that specifically indicates
      abundance of mitochondria. The CE-LIF analysis of mitochondrial properties, based
      on the individual mitochondrial determinations, has a wider scope than the
      average values determined by enzymatic or bulk protein assays.

PMID- 11444810
TI  - Light-induced activation of an inert surface for covalent immobilization of a
      protein ligand.
AB  - A simple and mild procedure is developed for the preparation of an activated
      polymer surface, used for immobilization of a protein ligand through a covalent
      linkage. Activation of the polymer surface is carried out by attaching an active
      functional group through 1-fluoro-2-nitro-4-azidobenzene (FNAB). UV irradiation
      of FNAB transforms its azido group into a highly reactive nitrene, which binds
      with the inert polymer surface, whereas the active fluoro group of FNAB, now part
      of the polymer, remains intact. Covalent linkage between the ligand and the inert
      surface is established through this active fluoro group in a thermochemical
      reaction. The photochemical step is carried out under dry conditions to exclude
      the possibility of undesirable reactions between the solvent and the highly
      reactive nitrene. The method can be used for activation of different inert
      polymer surfaces having carbon hydrogen bonds. The efficacy of our method is
      demonstrated by immobilizing horseradish peroxidase on an activated polystyrene
      surface. The enzyme, immobilized through the photolinker, is found to give a
      twofold increase in absorbance with the substrate as compared to the directly
      adsorbed enzyme. The method may have many applications in the preparation of
      bioreactors, biostrips, and biosensors, and in diagnostic tests involving the
      ELISA technique.

PMID- 11444811
TI  - Evaluation of two synthetic glucose probes for fluorescence-lifetime-based
      sensing.
AB  - We evaluated two anthracene derivatives with covalently attached boronic acid
      groups for fluorescence-lifetime-based sensing of glucose. These anthracene
      derivatives also contained alkyl amino groups, which quenched the anthracene
      emission by photo-induced electron transfer. Both anthracene derivatives
      displayed increased intensities and lifetime in the presence of glucose, as seen
      from the frequency-domain measurements. A fluorescence lifetime change from 9.8
      to 12.4 and 5.7 to 11.8 ns is observed, after the addition of glucose, for the
      anthracene substituted with one and two boronic acid groups, respectively. This
      results in a change in the phase angle up to 15 degrees and 30 degrees and in the
      modulation up to 12 and 25% at 30 MHz for these compounds, respectively.
      Titration curves in the presence of BSA and micelles are also presented to show
      the potential interferences from biomolecules. Dissociation constants were
      evaluated for both compounds, and association with glucose was found to be
      reversible. Importantly, the apparent glucose binding constants are about 5- to
      10-fold smaller with phase, modulation, or mean lifetime than with intensities
      measurements, shifting the glucose-sensitive range to physiological values.
      Combining these results and the use of a simple UV-LED as excitation source, the
      results show an interesting potential of these two compounds in the development
      of lifetime base devices using synthetic probes for glucose.

PMID- 11444812
TI  - A high-performance liquid chromatography radio method for determination of L
      ascorbic acid and guanosine 5'-diphosphate-l-galactose, key metabolites of the
      plant vitamin C pathway.
AB  - A simple, rapid, and quantitative high-pressure liquid chromatography radio
      method is described for the determination of in vivo (14)C-labeled l-ascorbate,
      dehydro-l-ascorbate, and total l-ascorbate of Arabidopsis thaliana cell
      suspensions upon incubation of cultures with exogenous d-[(14)C]mannose. The same
      radio-HPLC conditions can be used to follow the products of in vitro enzymatic
      conversions of GDP-d-mannose by enzyme extracts of A. thaliana, namely GDP-l
      galactose, GDP-4"-keto,6"-deoxy-d-mannose, and GDP-l-fucose. In particular, an
      accurate assay for GDP-d-mannose 3",5"-epimerase, a key enzyme of the plant
      vitamin C pathway, is presented.

PMID- 11444813
TI  - Cloning of random oligonucleotides to create single-insert plasmid libraries.
AB  - Random double-stranded oligonucleotides are useful reagents to identify the
      optimal binding sites for DNA-binding proteins, such as transcriptional
      activators. Some applications require ligation of random oligonucleotides to form
      plasmid-based libraries such as the yeast one-hybrid system, where the activation
      of a cloned DNA sequence from a library of random DNA-binding sequences activates
      a reporter gene. Current theories do not account for the low efficiencies of
      oligonucleotide-based plasmid library construction methods. We developed a
      technique to clone single oligonucleotides into plasmid vectors with high
      efficiency that predictably results in only one oligonucleotide insert per colony
      and used this method to clone a yeast one-hybrid library. This method, either as
      presented or with modifications, should be suitable for any situation where high
      efficiency cloning of single oligonucleotide inserts is desired.

PMID- 11444814
TI  - A substrate phage enzyme-linked immunosorbent assay to profile panels of
      proteases.
AB  - It is estimated that proteases comprise nearly 2% of the human genome. Given that
      the primary structure of all known proteases will soon be available, an important
      challenge is to define the structure-activity relationships that govern substrate
      hydrolysis. Ideally this would be accomplished on a genome-wide scale. To this
      end, we have developed a one-pot phage selection system that yields the substrate
      recognition profile of multiple proteases from a single round of selection. The
      system meets five key criteria: (i) multiple proteases can be analyzed
      simultaneously, (ii) prior knowledge of substrate preference is not required,
      (iii) information regarding substrate preferences on both side of the scissile
      bond is obtained, (iv) the system yields selective substrates that distinguish
      closely related proteases, and (v) semiquantitative information on substrate
      hydrolysis is obtained, allowing for the assignment of initial rank-order
      preferences. As an illustration, a phage selection with a mixture of thrombin and
      factor Xa (serine proteases) along with matrix-metalloproteinase-9 and atrolysin
      C (metalloproteinases) was performed. Peptide substrates were identified that (i)
      have high k(cat)/K(m) ratios, (ii) are selective for individual proteases, and
      (iii) match the sequences of known physiological substrates.

PMID- 11444815
TI  - Homogenization of tissue samples using a split-pestle.

PMID- 11444816
TI  - Quantitative measurement of radioactive phosphorylated proteins in wet
      polyacrylamide gels.

PMID- 11444817
TI  - Determination of complement of mRNA encoding inositol 1,4,5-trisphosphate
      receptor isoforms in rat tissues using relative-polymerase chain reaction.

PMID- 11444818
TI  - A method for quantitative extraction of sphingosine 1-phosphate into organic
      solvent.

PMID- 11444820
TI  - Dominant negative farnesyltransferase alpha-subunit inhibits insulin mitogenic
      effects.
AB  - Farnesylation of p21Ras is required for translocation to the plasma membrane and
      subsequent activation by growth factors. Previously we demonstrated that insulin
      stimulates the phosphorylation of farnesyltransferase (FTase) and its activity,
      whereby the amount of farnesylated p21Ras anchored at the plasma membrane is
      increased. Herein we report that substitution of alanine for two serine residues
      (S60A)(S62A) of the alpha-subunit of FTase creates a dominant negative (DN)
      mutant. VSMC expressing the FTase alpha-subunit (S60A)(S62A) clone showed a 30%
      decreased basal FTase activity concurrent with a 15% decrease in the amount of
      farnesylated p21Ras compared to controls. Expression of alpha-subunit (S60A,S62A)
      blunted FTase phosphorylation and activity in the presence of hyperinsulinemia,
      and inhibited insulin-stimulated increases in farnesylated p21Ras. Insulin
      stimulated VSMC expressing the FTase alpha-subunit (S60A,S62A) showed decreased
      (i) phosphorylation of FTase, (ii) FTase activity, (iii) amounts of farnesylated
      p21Ras, (iv) DNA synthesis, and (v) migration. Thus, down-regulation of FTase
      activity appears to mitigate the potentially detrimental mitogenic effects of
      hyperinsulinemia on VSMC.

PMID- 11444821
TI  - SNAP-29 is a promiscuous syntaxin-binding SNARE.
AB  - SNARE proteins are key regulators of membrane fusion and are proposed to dictate
      the specificity with which particular vesicles fuse with particular target
      organelles. On intracellular organelles that serve as targets for transport
      vesicles, organelle-specific syntaxins form heterodimers with either SNAP-23 or
      its recently described homolog SNAP-29. We have performed a variety of in vitro
      and in vivo binding assays in an attempt to determine whether SNAP-23 and SNAP-29
      differ in their ability to form binary SNARE complexes with different
      intracellular syntaxins. While SNAP-23 preferentially binds to plasma membrane
      localized syntaxins, SNAP-29 binds to both plasma membrane and intracellular
      syntaxins equally well. Furthermore, binding to SNAP-29 augments the ability of
      syntaxin to bind to vesicle-associated SNAREs and the presence of vesicle SNAREs
      dramatically increases SNAP-29 binding to syntaxin. These data suggest that SNAP
      23 preferentially regulates plasma membrane-vesicle fusion events while SNAP-29
      plays a role in the maintenance of various intracellular protein trafficking
      pathways.

PMID- 11444822
TI  - Low asialoglycoprotein receptor expression as markers for highly proliferative
      potential hepatocytes.
AB  - Development of a reliable method to isolate highly proliferative potential
      hepatocytes will provide insight into the molecular mechanisms of liver
      regeneration, as well as proving crucial for the development of a biohybrid
      artificial liver. The aim of this study is to isolate highly proliferative, e.g.,
      progenitor-like, hepatocytes. To this end, we fractionated hepatocytes expressing
      low and high levels of the asialoglycoprotein receptor (ASGP-R) based on the
      difference in their adhesion to poly[N-p-vinylbenzyl-O-beta-d-galactopyranosyl-(1
      ->4)-d-gluconamide] (PVLA), and examined the proliferative activity and gene
      expression of these fractionated hepatocytes. The results showed that
      approximately 0.5 to 1% of the total number of hepatocytes, which showed low
      adhesion to PVLA, expressed low levels of the ASGP-R, while the rest of
      hepatocyte population with high adhesion to PVLA expressed high levels of the
      ASGP-R. Interestingly hepatocytes with low ASGP-R expression levels had much
      higher DNA synthesizing activity (i.e., are much more proliferative) than those
      with high ASGP-R expression levels. Moreover, hepatocytes with low ASGP-R
      expression levels expressed higher levels of epidermal growth factor receptor
      (EGF-R), CD29 (beta1 integrin) and CD49f (alpha6 integrin) and lower levels of
      glutamine synthetase than those with high ASGP-R expression. These findings
      suggested that hepatocytes with low adhesion to PVLA due to their low ASGP-R
      expression could be potential candidates for progenitor-like hepatocytes due to
      their high proliferative capacity; hence, the low expression of the ASGP-R could
      be a unique marker for progenitor hepatocytes. The isolation of hepatocytes with
      different functional phenotypes using PVLA may provide a new research tool for a
      better understanding of the biology of hepatocytes and the mechanisms regulating
      their proliferation and differentiation in health and disease.

PMID- 11444823
TI  - Involvement of p-15(INK4b) and p-16(INK4a) gene expression in saikosaponin a and
      TPA-induced growth inhibition of HepG2 cells.
AB  - Saikosaponin a, a purified ingredient of Chinese herb with known antitumor
      activity, can inhibit cell growth and DNA synthesis of hepatoma cell line HepG2.
      Both mRNA and protein of the CDK inhibitor p-16(INK4a) and p-15(INK4b) in HepG2
      were greatly induced by saikosaponin a while that of p-21(CIP), p-27(KIP) and
      other cell cycle related genes were not. In addition, reduced phosphorylation of
      RB protein is observed in saikosaponin a-treated HepG2. Staurosporin, one of the
      PKC inhibitors, significantly prevented the saikosaponin a induced growth
      inhibition suggesting PKC pathway be involved. On the other hand, the phorbol
      ester tumor promoter TPA (12-O-Tetredecanolyphorbol 13-acetate) also inhibited
      HepG2 growth and specifically induced p-16(INK4a) and p-15(INK4b) mRNA
      expression. The results suggest that both saikosaponin a and TPA-induced HepG2
      growth inhibition are associated with p-15(INK4a) and p-16(INK4b) gene expression
      and might be mediated by PKC signaling pathway.

PMID- 11444824
TI  - Mitochondria isolated from liver contain the essential factors required for
      RNA/DNA oligonucleotide-targeted gene repair.
AB  - Chimeric RNA/DNA oligonucleotides (ONs) have been used successfully for site
      specific modifications of episomal and chromosomal DNA in eukaryotic cells. We
      explored the possibility of applying this technique to mitochondrial DNA, as
      single-nucleotide defects in this genome are associated with a series of human
      diseases. Therefore, we determined whether mitochondria possess the enzymatic
      machinery for chimeric ON-mediated DNA alterations. We utilized an in vitro DNA
      repair assay and an Escherichia coli readout system with mutagenized plasmids
      carrying point mutations in antibiotic resistance genes. RNA/DNA ONs were
      designed to correct the defects and restore kanamycin and tetracyclin resistance.
      Using this system, we demonstrated that extracts from highly purified rat liver
      mitochondria possess the essential enzymatic activity to mediate precise single
      nucleotide changes. Interestingly, the frequency of gene conversion was similar
      in both mitochondrial and nuclear extracts, as well as from quiescent and
      regenerating liver. The results indicate that mitochondria contain the machinery
      required for repair of genomic single-point mutations, and suggest that RNA/DNA
      ONs may provide a novel approach to the treatment of certain mitochondrial-based
      diseases.

PMID- 11444825
TI  - Downregulation of p21/WAF1 expression by thymidylate synthase.
AB  - We developed a cell system where expression of thymidylate synthase (TS), an
      enzyme essential for DNA synthesis, can be modulated by a Zn(2+)-inducible
      promoter in MCF-7 cells. We found that overexpression of TS resulted in
      downregulation of p21 protein and mRNA levels. Statistical analysis demonstrated
      a significant downregulation of p21, but not a statistically significant decrease
      in p53 protein levels following TS induction. Since p21 is known to be
      transcriptionally activated by p53, these results suggest that TS downregulation
      of p21 may be occurring through a p53-independent mechanism in this in vitro cell
      system. In addition, cell cycle analysis demonstrated that downregulation of p21
      by TS resulted in a decreased G(1)/S ratio in MCF-7 cells.

PMID- 11444826
TI  - Efficient accommodation of recombinant, foot-and-mouth disease virus RGD peptides
      to cell-surface integrins.
AB  - The engineering of either complete virus cell-binding proteins or derived ligand
      peptides generates promising nonviral vectors for cell targeting and gene
      therapy. In this work, we have explored the molecular interaction between a
      recombinant, integrin-binding foot-and-mouth disease virus RGD peptide displayed
      on the surface of a carrier protein and its receptors on the cell surface. By
      increasing the number of viral segments, cell binding to recombinant proteins was
      significantly improved. This fact resulted in a dramatic growth stimulation of
      virus-sensitive BHK(21) cells but not virus-resistant HeLa cells in protein
      coated wells. Surprisingly, growth stimulation was not observed in vitronectin
      coated plates, suggesting that integrins other than alpha(v)beta(3) could be
      involved in binding of the recombinant peptide, maybe as coreceptors. On the
      other hand, both free and cell-linked integrins did not modify the enzymatic
      activity of RGD-based enzymatic sensors that contrarily, were activated by the
      induced fit of anti-RGD antibodies. Those findings are discussed in the context
      of a proper mimicry of the unusually complex architecture of this cell-binding
      site as engineered in multifunctional proteins.

PMID- 11444827
TI  - cAMP protection of pancreatic cancer cells against apoptosis induced by ERK
      inhibition.
AB  - Large increases in cAMP concentration inside the cell are generally growth
      inhibitory for most cell lines of mesenchymal and epithelial origin. Moreover,
      recent data suggest a role of cAMP in survival of different cell types. Herein,
      the ability of forskolin (an adenylyl cyclase activator) and IBMX (3-isobutyl-1
      methylxanthine) (a phosphodiesterase inhibitor) to modulate cell cycle
      progression and survival of human pancreatic cancer cells was evaluated. We
      showed that forskolin + IBMX inhibited serum-induced ERK activities, Rb
      hyperphosphorylation, Cdk2 activity, and p27(Kip1) downregulation and caused G1
      arrest in MIA PaCa-2 cells. Furthermore, forskolin + IBMX protected pancreatic
      cells against apoptosis induced by prolonged inhibition of ERK activities by
      preventing Bcl-X(L) downregulation, activation of caspases 3, 6, 8, and 9, and
      PARP cleavage and by inducing Bad phosphorylation (ser112). Taken together, our
      data demonstrate for the first time that cAMP is an inhibitor of cell cycle
      progression and apoptosis in human pancreatic cancer cells.

PMID- 11444828
TI  - Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA
      induced inhibition of fatty acid oxidation and cytotoxicity.
AB  - Inhibition of fatty acid synthase (FAS) induces apoptosis in human breast cancer
      cells in vitro and in vivo without toxicity to proliferating normal cells. We
      have previously shown that FAS inhibition causes a rapid increase in malonyl-CoA
      levels identifying malonyl-CoA as a potential trigger of apoptosis. In this study
      we further investigated the role of malonyl-CoA during FAS inhibition. We have
      found that: [i] inhibition of FAS with cerulenin causes carnitine
      palmitoyltransferase-1 (CPT-1) inhibition and fatty acid oxidation inhibition in
      MCF-7 human breast cancer cells likely mediated by elevation of malonyl-CoA; [ii]
      cerulenin cytotoxicity is due to the nonphysiological state of increased malonyl
      CoA, decreased fatty acid oxidation, and decreased fatty acid synthesis; and
      [iii] the cytotoxic effect of cerulenin can be mimicked by simultaneous
      inhibition of CPT-1, with etomoxir, and fatty acid synthesis with TOFA, an acetyl
      CoA carboxylase (ACC) inhibitor. This study identifies CPT-1 and ACC as two new
      potential targets for cancer chemotherapy.

PMID- 11444829
TI  - Isolation and characterization of an apoptosis-inhibiting component from the
      hemolymph of Bombyx mori.
AB  - Silkworm (Bombyx mori) hemolymph showed an apoptosis-inhibiting activity in
      insect cells (Sf 9) infected with baculovirus (AcNPV). The addition of silkworm
      hemolymph into the culture medium increased the host cell longevity due to its
      apoptosis-inhibition activity. Components with an apoptosis-inhibiting effect
      were purified from the silkworm hemolymph by heat treatment, gel-filtration
      chromatography, and ion-exchange chromatography. The component with highest
      activity was characterized by periodic acid-Schiff staining, isoelectric
      focusing, MALDI-TOF-mass spectrometry, and N-terminal sequencing and was found to
      be a nonglycosylated monomeric protein with a molecular weight of ca. 28,000 Da.

PMID- 11444830
TI  - Molecular cloning and characterization of a novel calcium/calmodulin-dependent
      protein kinase II inhibitor from human dendritic cells.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is a widely distributed
      protein kinase that regulates numerous physiological functions. Inhibitors of
      CaMKII are useful tools for investigating the CaMKII functions. Here we
      identified a novel CaMKII inhibitor protein (CaM-KIIN) from the human dendritic
      cell cDNA library by large-scale random sequencing. Human CaM-KIIN contains 79
      amino acids, which shares 98% identity and 98% positives with rat CaMKII
      inhibitor protein beta and 65% identity and 78% positives with rat CaMKII
      inhibitor alpha. Human CaM-KIIN mRNA expression was detectable in various tissues
      and cell lines by Northern blot and RT-PCR. To investigate its biological
      functions, full-length human CaM-KIIN was overexpressed in colon adenocarcinoma
      LoVo cells. When expressed in LoVo cells, it could inhibit cell proliferation,
      block cell growth, and decrease the viable cell number. These results
      characterize a potential cellular inhibitor protein of CaMKII that plays an
      important role in the regulation of cell growth.

PMID- 11444831
TI  - A novel secreted tumor antigen with a glycosylphosphatidylinositol-anchored
      structure ubiquitously expressed in human cancers.
AB  - In a search for novel genes expressed in human cancers, we identified one gene
      from an assembled expressed sequence tag database. Northern blot analysis
      revealed that the gene, termed alcan, was expressed in various types of human
      cancer cell lines and in the fetus, but not in normal tissues. The alcan gene is
      located on chromosome 6 and is encoded on a 246-amino-acid protein with weak
      homology to classical major histocompatibility complex class I. Its gene product,
      ALCAN, had hydrophobic amino acid clusters at both the N- and C-terminal regions
      and was predicted to be a glycosylphosphatidylinositol (GPI)-anchored membrane
      protein. Flow cytometric analysis revealed that ALCAN was detected on the surface
      of human cancer cells and on alcan-transfected CHO-K1 cells. ALCAN was also
      secreted from these cells, suggesting that some portion of the molecules was
      secreted by enzymatic cleavage by, for example, phospholipases. Mutational
      analysis of ALCAN suggested that the GPI-anchored position was the Ser(216)
      residue. These findings indicate that ALCAN may be a potential target for cancer
      diagnosis or therapy.

PMID- 11444832
TI  - Perlustrin, a Haliotis laevigata (abalone) nacre protein, is homologous to the
      insulin-like growth factor binding protein N-terminal module of vertebrates.
AB  - The 84-amino-acid-long sequence of perlustrin showed homology of the abalone
      nacre protein to the N-terminal domain of mammalian insulin-like growth factor
      binding proteins (IGFBPs). Despite the evolutionary distance between mollusks and
      mammals, the sequence identity was 40% including 12 conserved cysteines. However,
      the residues which were suggested recently to bind IGF-II in a complex with IGFBP
      5 were conserved only partially. Nevertheless, perlustrin bound human IGFs with
      K(D) approximately 10(-7) M. This was the same affinity range as measured before
      for the interaction of isolated IGFBP-5 N-terminal domains with IGFs. Moreover,
      perlustrin bound bovine insulin with only approximately two- to sevenfold lower
      affinity than IGFs. Sequence similarity and growth factor binding identified
      perlustrin unequivocally as a member of the IGFBP family, the first found in an
      invertebrate biomineral. Nacre is known to contain proteinaceous factors which
      promote bone formation in vitro and in vivo. Bone contains IGFBPs which influence
      bone metabolism in many ways by modulating either IGF effects or IGF
      independently. Thus, perlustrin may provide a first clue at the molecular level
      to what these two phylogenetically rather distant biomineralization systems have
      in common.

PMID- 11444833
TI  - Expanding role of G proteins in tight junction regulation: Galpha(s) stimulates
      TJ assembly.
AB  - Multiple signaling mechanisms regulate epithelial cell tight junction (TJ)
      assembly and maintenance. Several G proteins are likely to regulate these
      processes, but only G(i/o) have been specifically tested. Treatment of MDCK cells
      with cholera toxin, a Galpha(s) activator, accelerated TJ development in the
      calcium switch as measured by the time to half-maximal [T(50) (H)]
      transepithelial resistance (TER). Galpha(s) was predominantly localized in the
      lateral membrane, but a fraction colocalizes with ZO-1 in the TJ. MDCK cell lines
      expressing epitope-tagged Galpha(s) and constitutively active (R201Calpha(s))
      showed a similar localization. TJ assembly was significantly faster in
      R201Calpha(s)-MDCK cell lines (T(50) (H) of 1.7 versus 3.3 h for controls)
      without detectable differences in cAMP levels. Confocal studies showed
      R201Calpha(s)-MDCK cells more rapidly localized ZO-1 and occludin into the
      developing TJ without affecting E-cadherin or Na(+)/K(+) ATPase localization.
      Endogenous Galpha(s) and R201Calpha(s) were immunoprecipitated with ZO-1 at
      baseline and during TJ assembly. The data supports a model of multiple Galpha
      subunits interacting with TJ proteins to regulate the assembly and maintenance of
      the TJ.

PMID- 11444834
TI  - Dimethyl sulfide, a volatile flavor constituent, is a slow-binding inhibitor of
      tyrosinase.
AB  - In this paper, the inhibition of tyrosinase by a volatile compound is kinetically
      analyzed for the first time. The results obtained show that the volatile flavor
      constituent dimethyl sulfide (DMS) inhibits the catecholase activity of
      tyrosinase in a nonclassical manner. A decrease in the initial velocity to a
      inhibited steady-state velocity can be observed within a few minutes. This time
      dependence, which is unaltered by prior incubation of the enzyme with the
      inhibitor, is consistent with a first-order transition. Both the initial and the
      constant rates decreased with increasing concentrations of inhibitor. The kinetic
      data obtained correspond to those for a postulated mechanism involving rapid
      formation of an enzyme-inhibitor complex that subsequently undergoes a relatively
      slow reversible reaction. These results, together with the high levels of DMS
      precursor in certain organisms, suggest a physiological role for this compound
      within plant tissues.

PMID- 11444835
TI  - Scavenging of peroxynitrite by phycocyanin and phycocyanobilin from Spirulina
      platensis: protection against oxidative damage to DNA.
AB  - Peroxynitrite (ONOO(-)) is known to inactivate important cellular targets and
      also mediate oxidative damage in DNA. The present study has demonstrated that
      phycocyanin, a biliprotein from spirulina platensis and its chromophore,
      phycocyanobilin (PCB), efficiently scavenge ONOO(-), a potent physiological
      inorganic toxin. Scavenging of ONOO(-) by phycocyanin and PCB was established by
      studying their interaction with ONOO(-) and quantified by using competition
      kinetics of pyrogallol red bleaching assay. The relative antioxidant ratio and
      IC(50) value clearly indicate that phycocyanin is a more efficient ONOO(-)
      scavenger than PCB. The present study has also shown that PCB significantly
      inhibits the ONOO(-)-mediated single-strand breaks in supercoiled plasmid DNA in
      a dose-dependent manner with an IC(50) value of 2.9 +/- 0.6 microM. These results
      suggest that phycocyanin, has the ability to inhibit the ONOO(-)-mediated
      deleterious biological effects and hence has the potential to be used as a
      therapeutic agent.

PMID- 11444836
TI  - Nuclear factor-kappab blockade attenuates but does not abrogate
      lipopolysaccharide-dependent tumor necrosis factor-alpha biosynthesis in alveolar
      epithelial cells.
AB  - We have investigated the role that the nuclear factor (NF)-kappaB plays in
      regulating the biosynthesis of tumor necrosis factor (TNF)-alpha, an inflammatory
      cytokine. Irreversible inhibition of the proteasome complex by carbobenzoxy-l
      leucyl-l-leucyl-l-leucinal (MG-132; 1-50 microM) had no inhibitory effect on LPS
      mediated TNF-alpha biosynthesis. Furthermore, selective inhibition of NF-kappaB
      by the action of caffeic acid phenylethyl ester (CAPE; 1-100 microM) and
      sulfasalazine (SSA; 0.1-10 mM), a potent and irreversible inhibitor of NF-kappaB,
      partially attenuated, but did not abolish, LPS-dependent TNF-alpha secretion.
      Incorporation of a selectively permeant inhibitor of NF-kappaB, SN-50 (1-20
      microM), a peptide which contains the nuclear localization sequence (NLS) for the
      p50 NF-kappaB subunit, and the amino-terminal sequence of Kaposi fibroblast
      growth factor to promote cell permeability, attenuated in a dose-dependent manner
      LPS-mediated release of TNF-alpha. It is concluded that the NF-kappaB pathway is
      partially implicated and that its blockade attenuates, but does not abrogate, LPS
      dependent TNF-alpha biosynthesis in alveolar epithelial cells.

PMID- 11444837
TI  - Myoglobin-catalyzed tyrosine nitration: no need for peroxynitrite.
AB  - The nitration of tyrosine residues in protein to yield 3-nitrotyrosine
      derivatives has been suggested to represent a specific footprint for
      peroxynitrite formation in vivo. However, recent studies suggest that certain
      hemoproteins such as peroxidases catalyze the H(2)O(2)-dependent nitration of
      tyrosine to yield 3-nitrotyrosine in a peroxynitrite-independent reaction.
      Because 3-nitrotyrosine has been shown to be present in the postischemic
      myocardium, we wished to assess the ability of myoglobin to catalyze the
      nitration of tyrosine in vitro. We found that myoglobin catalyzed the oxidation
      of nitrite and promoted the nitration of tyrosine. Both nitrite oxidation and
      tyrosine nitration were H(2)O(2)-dependent and required the formation of ferryl
      (Fe(+4)) myoglobin. In addition, nitrite oxidation and tyrosine nitration were pH
      dependent with a pH optimum of approximately 6.0. Taken together, these data
      suggest that the acidic pH and low oxygen tension produced during myocardial
      ischemia will facilitate myoglobin-catalyzed, peroxyntrite-independent formation
      of 3-nitrotyrosine.

PMID- 11444838
TI  - GroEL-assisted dehydrogenase folding mediated by coenzyme is ATP-independent.
AB  - It has been commonly accepted that GroEL functions as a chaperone by modulation
      of its affinity for folding intermediates through binding and hydrolysis of ATP.
      However, we have found that NAD, as a coenzyme of d-glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), also stimulates the discharge of GAPDH folding
      intermediate from its stable complex with GroEL formed in the absence of ATP and
      assists refolding with the same yield as ATP/Mg(2+) does. The reactivation
      further increases when ATP is also present, but addition of Mg(2+) has no more
      effect. NADP, a coenzyme of glucose-6-phosphate dehydrogenase, also releases its
      folding intermediates from GroEL and increases reactivation. Different from ATP,
      NAD triggers the release of GAPDH intermediates bound by GroEL via binding with
      GAPDH itself but not with GroEL, and the released intermediates all folded to
      native molecules without the formation of aggregation. The collaborative effects
      of coenzyme and GroEL mediate GroEL-assisted dehydrogenase folding in an ATP
      independent way.

PMID- 11444839
TI  - PKCdelta-dependent deubiquitination and stabilization of Gadd45 in A431 cells
      overexposed to EGF.
AB  - Epidermal growth factor (EGF) receptor-overexpressing p53-deficient A431 cells
      response to toxic dose of EGF by G1 arrest and apoptosis was studied. We
      previously reported an increased expression of growth arrest and DNA-damage
      inducible gene, Gadd45, in EGF-overexposed A431 cells. The mechanism for this
      induction was increased half-lives of mRNA and protein. In this study, using
      phorbol ester (a PKC activator) and specific inhibitors of PKC isoforms, we
      showed that protein kinase C-delta (PKCdelta) was involved in the increase of
      Gadd45 protein stability. We further demonstrated that Gadd45 is ubiquitinated
      and is regulated by proteolysis. While EGF induced ubiquitination of total
      cellular proteins, there was a decrease in Gadd45 ubiquitination, which could be
      inhibited by Rottlerin, a PKCdelta-specific inhibitor. These results suggest that
      an increase in Gadd45 stability may involve PKCdelta-dependent ubiquitin
      proteasome pathway.

PMID- 11444840
TI  - Genomic instability in a PARP-1(-/-) cell line expressing PARP-1 DNA-binding
      domain.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear DNA binding protein that
      participates in processes involving nicking and resealing DNA strands. A
      genomically unstable subpopulation of PARP-1(-/-) cells has recently been
      described, which disappears after stable transfection of the cells with complete
      PARP-1 cDNA. Here we investigate the role played by PARP-1 in the maintenance of
      genomic stability, independently of its enzymatic activity. We used a PARP-1
      deficient cell line to express a DNA construct encoding the PARP-1 DNA-binding
      domain (DBD) fragment and one encoding the mutant DBDbd-, defective in binding to
      DNA strand breaks. We found that, in the absence of DNA damage, expression of DBD
      or DBDbd- mutant induces increased genomic instability in the PARP-1(-/-) cells.
      These results suggest that the DBD fragment of PARP-1, apart from its classical
      role of nick detection and DNA binding, is likely to participate in molecular
      complexes with proteins involved in genomic integrity.

PMID- 11444841
TI  - Tocopherol-associated protein is a ligand-dependent transcriptional activator.
AB  - Vitamin E is a term that encompasses a group of potent, lipid-soluble, chain
      breaking antioxidants. Structural analysis reveals that molecules having vitamin
      E activity include four isomers (alpha, beta, gamma, and delta) of both
      tocopherols and tocotrienols. Alpha-tocopherol has been shown to have the highest
      biological vitamin E activity in mammalian tissues based on fetal resorption
      assays, and it reverses vitamin E deficiency symptoms. Although the molecular
      functions fulfilled specifically by alpha-tocopherol have yet to be fully
      described, it is unlikely that they are limited to general antioxidant functions.
      Here we show the functional characterization of alpha-tocopherol associated
      protein, TAP, which displays significant sequence similarity to the alpha
      tocopherol transfer protein. Ligand competition analysis showed that recombinant
      TAP binds to alpha-tocopherol but not to other isomers of tocopherols. Using GFP
      fusion protein expression system, we observed that TAP translocates from cytosol
      to nuclei in alpha-tocopherol-dependent fashion. Transient transfection
      experiment showed that TAP activates transcription of the reporter gene in alpha
      tocopherol-dependent manner. These results suggest that the biological function
      of alpha-tocopherol is not only as an antioxidant but also as a transcriptional
      regulator of gene expression via association with a transcription factor TAP.

PMID- 11444842
TI  - Induction of human matrix metalloproteinase-12 gene transcriptional activity by
      GM-CSF requires the AP-1 binding site in human U937 monocytic cells.
AB  - Matrix metalloproteinase-12 (MMP-12) is critical for the migration of
      monocytes/macrophages into inflammatory sites through the basement membranes. We
      previously reported that MMP-12 expression was initially induced by granulocyte
      macrophage colony-stimulating factor (GM-CSF) in human peripheral blood monocytes
      and U937 monocytic cells. To further elucidate the molecular mechanism for the
      regulation of MMP-12 expression by GM-CSF in monocytes, we determined the
      sequence requirements for the MMP-12 gene transcriptional response of U937
      monocytic cells to GM-CSF by using luciferase reporter and electrophoretic
      mobility shift assays. A series of 5'-deletion and site-directed mutation of the
      human MMP-12 promoter demonstrated that an AP-1 site spanning the -81 to -75-bp
      region is critical for the induction of MMP-12 promoter activity by GM-CSF. The
      electrophoretic mobility shift assay revealed that AP-1 binding activity was
      increased by GM-CSF treatment and that the AP-1 complex induced by GM-CSF
      consisted of multiple Jun and Fos isoforms. These results indicate that MMP-12
      expression in U937 monocytes was initially induced by GM-CSF through the AP-1
      binding activity.

PMID- 11444843
TI  - Acid-induced polymerization of the group 5 mite allergen from Dermatophagoides
      pteronyssinus.
AB  - House dust mites are the most important source of indoor allergens and cause
      allergic diseases. Our studies here suggest that the group 5 allergen from
      Dermatophagoides pteronyssinus (Der p 5) is monomeric at neutral pH, but forms
      filaments at low pH. Circular dichroism measurements show Der p 5 is a helical
      protein, and the protein sequence reveals Der p 5 contains coiled-coil helices.
      The acid-induced filament assembly could be explained in part by the high content
      of charged residues (40%) in the coiled-coil structure. Interestingly, some of
      the known Dermatophagoides allergens also contain a heptad repeat, which could
      potentially form coiled coils. Therefore, coiled-coil helices may be one of the
      common structural motifs of mite allergens that contribute to their
      allergenicity.

PMID- 11444844
TI  - Tyrosinase degradation via two pathways during reverse translocation to the
      cytosol.
AB  - Previous studies established that after inhibition of proteasome activity,
      tyrosinase could be detected in the cytosol after initial translation in the
      endoplasmic reticulum (ER), with a molecular weight consistent with that of a
      full-length, deglycosylated polypeptide. Here we show that most of these
      molecules are glycosylated, but have been proteolyzed at the carboxyl terminus by
      a protease that is insensitive to proteasome inhibitors. We also demonstrate the
      inhibitor-dependent accumulation of a membrane species that appears structurally
      homologous to the glycosylated and partially proteolyzed cytosolic form. Under
      some circumstances, cytosolic tyrosinase that had been deglycosylated and not
      proteolyzed prior to proteasomal degradation could also be detected. The presence
      of cytosolic tyrosinase was dependent upon glycosylation of the molecule during
      synthesis in the ER. These results suggest the existence of at least two
      alternative pathways for degradation of tyrosinase in the cytosol.

PMID- 11444845
TI  - Identification of three new splice variants of the SNARE protein SNAP-23.
AB  - SNAP-23 has an important role in protein-trafficking processes in mammalian cells
      and until yet two isoforms of SNAP-23 (SNAP-23a and SNAP-23b) have been
      described. In the present report, we have identified the existence of three new
      SNAP-23 isoforms (named SNAP-23c, SNAP-23d, and SNAP-23e), which arise from
      alternative splicing. By RT-PCR all five splice variants were shown to be
      expressed in four different human inflammatory cells (eosinophils, basophils,
      neutrophils, and peripheral blood mononuclear cells). Transfection of the human
      basophilic KU-812 cell line with plasmid constructs containing the cDNAs of the
      five splice variants located SNAP-23a and SNAP-23b primarily in the plasma
      membrane. The other three splice variants were localized both intracellularly and
      in the plasma membrane.

PMID- 11444846
TI  - Macrophage colony-stimulating factor suppresses osteoblast formation.
AB  - We provide the first evidence that the bone marrow-derived cytokine, macrophage
      colony-stimulating factor (M-CSF), inhibits the formation of bone-forming
      osteoblasts. We examined both osteoclast and osteoblast formation in primary rat
      bone marrow cultures. As expected, M-CSF together with osteoprotegerin ligand
      (OPGL) markedly accelerated osteoclastogenesis. In contrast, treatment with M-CSF
      alone yielded no osteoclasts at any time. The most striking and novel observation
      was that M-CSF with or without OPGL dramatically suppressed osteoblast formation.
      In separate experiments, estradiol markedly suppressed osteoclast formation in
      the M-CSF/OPGL-treated cultures independently of osteoblasts. Consistent with
      this was the expression of estrogen receptor-alpha (ERalpha) and ERbeta mRNA in
      osteoclast precursors. We therefore conclude that in addition to the well-known
      action of M-CSF to modulate osteoclastogenesis, this cytokine may also regulate
      osteoblast formation.

PMID- 11444847
TI  - New insights into the regulation of cathepsin K gene expression by
      osteoprotegerin ligand.
AB  - Cathepsin K plays a key role in bone resorption. We provide the first evidence
      that osteoprotegerin ligand (OPGL), a critical pro-resorptive cytokine, acutely
      stimulates the expression of cathepsin K in osteoclasts. We used in situ RT-PCR
      and real time quantitative RT-PCR to analyze cathepsin K gene expression. OPGL
      enhanced cathepsin K mRNA levels in mature osteoclasts isolated from rat neonatal
      long bones. OPGL together with macrophage colony-stimulating factor (M-CSF) also
      stimulated cathepsin K gene expression in monocytic cells and multinucleate
      osteoclasts in bone marrow cultures. Real time quantitative RT-PCR demonstrated
      high levels of cathepsin K mRNA in bone marrow cultures, paralleling the degree
      of osteoclastogenesis. We therefore suggest that OPGL enhances bone resorption,
      at least in part, by inducing cathepsin K gene expression.

PMID- 11444848
TI  - Expression, function, and clinical implications of the estrogen receptor beta in
      human lung cancers.
AB  - The higher frequency of human lung adenocarcinoma in females than in males,
      strongly suggests the involvement of gender dependent factors in the etiology of
      this disease. This is the first investigation of estrogen receptor (ER) beta in
      human lung. Immunohistochemical staining revealed ERbeta expression in normal
      lung and in atypical adenomatous hyperplasia (AAH), considered as a precancerous
      lesion for adenocarcinomas. Adenocarcinomas showed significantly higher
      expression of ERbeta than squamous cell carcinomas. On the contrary, ERalpha
      expression was not detected in all cases. The functional integrity of ERbeta such
      as the binding ability to estrogen responsive element (ERE) and transcriptional
      activity was confirmed using a human lung cancer cell line, RERF-LC-OK. Colony
      formation of this cell was significantly reduced in the presence of pure
      antiestrogen. We conclude that ERbeta, but not ERalpha, is present in lung
      tissues with an important physiological function in normal lung. Furthermore,
      ERbeta may play a role in growth and development of adenocarcinomas.

PMID- 11444849
TI  - The effect of modifications of the charged residues in the transmembrane helices
      on the transport activity of the melibiose carrier of Escherichia coli.
AB  - The melibiose transport carrier of Escherichia coli (coded by melB gene) is a
      cotransport system which couples the transport of a-galactosides to protons,
      sodium, or lithium ions. The charged amino acid residues in membrane-spanning
      helices are of considerable interest because many of them have important function
      in substrate recognition. In most cases changing these charged residue to an
      uncharged residue (cysteine) results in total loss of activity. In this
      communication we describe experiments in which the cysteine substitution for a
      charged residue was chemically changed by sulfhydryl reagents (MTSEA and MTSET to
      restore a positive charge and MTSES a negative charge) or by iodoacetic acid or
      through oxidation by hydrogen peroxide so as to regain the original negative
      charge. In two cases (D55C and D124C) the reconstructed negative charges via the
      oxidation of the thiol to the sulfinic and/or sulfonic acid resulted in partial
      recovery of transport: D55C up to 27% of the normal and D124C up to 4% of the
      normal in melibiose accumulation; D55C up to 36% of the normal and D124 up to
      4.5% of the normal in downhill transport. Sulfhydryl reagents and iodoacetic acid
      failed to recover transport in all cases. We infer that the configurations of the
      charges as well as the structure of the side chains that carry them are critical
      in the maintenance of the transport.

PMID- 11444850
TI  - Differential phosphorylation of paxillin in response to surface-bound serum
      proteins during early osteoblast adhesion.
AB  - An early signaling event during the adhesion and spreading of cells is integrin
      mediated tyrosine phosphorylation of the cytoskeletal adaptor protein paxillin
      and the non-receptor tyrosine kinase pp125(FAK) at focal contacts. To determine
      the influence of surface-charge and -adsorbed adhesion proteins on this signaling
      pathway, paxillin phosphorylation was examined during attachment of MC3T3-E1
      osteoblast-like cell onto charged and uncharged polystyrene, and on adsorbed
      layers of serum proteins, fibronectin (Fn), vitronectin (Vn), a mixture of Fn and
      Vn, and albumin. Paxillin phosphorylation was induced 2.4-fold (P < 0.05) on
      charged vs uncharged polystyrene only in the presence of serum proteins.
      Activation of paxillin via Fn or Vn alone, or in combination, resulted in
      significantly lower phosphorylation signals compared to whole serum (41 +/- 6.9%,
      P < 0.05, 45 +/- 5.9%, P < 0.05, and 76 +/- 9.8%, P < 0.075, respectively).
      Confocal laser microscopy confirmed increased co-localization of phosphotyrosine
      and paxillin at protruding lamellopodia of spreading osteoblasts on charged vs
      uncharged serum-pretreated polystyrene. Taken together, these data suggest that
      subtle differences in surface characteristics mediate effects on adhering cells
      via adsorbed serum proteins involving the cytoskeletal adaptor protein paxillin.

PMID- 11444851
TI  - Identification and characterization of GDP-d-mannose 4,6-dehydratase and GDP-l
      fucose snthetase in a GDP-l-fucose biosynthetic gene cluster from Helicobacter
      pylori.
AB  - In this study two open reading frames, namely HP0044 and HP0045 from H. pylori,
      were cloned and overexpressed in E. coli. The two recombinant proteins were
      demonstrated to have GDP-d-mannose 4,6-dehydratase (GMD) and GDP-l-fucose
      synthetase (GFS) activities, respectively. The recombinant GMD was a tetramer and
      had an optimum pH of 6.5. Exogenous NADP(+) was essential for its activity. The
      K(m) and K(cat) for GDP-d-mannose were 117.3 microM and 0.27 s(-1), respectively.
      The recombinant GFS was a homodimer with an optimum pH of 8.0. The K(m) and
      K(cat) for GDP-4-keto-6-deoxy-d-mannose were 64.08 microM and 0.75 s(-1),
      respectively. It can use both NADPH and NADH, but less efficient with the latter.
      Amino acid sequence alignment and phylogenetic analysis showed that H. pylori GFS
      was highly homologous to the GFS of E. coli O111 and both of them were located on
      a separate phylogenetic branch from other GFS. The unique clustering and origin
      of the two genes were also discussed.

PMID- 11444852
TI  - Change in expression of GBP28/adiponectin in carbon tetrachloride-administrated
      mouse liver.
AB  - GBP28 (gelatin-binding protein of 28 kDa)/adiponectin is an adipocyte-producing
      plasma protein proposed to interact with the extracellular matrix. To examine the
      production of GBP28 in non-adipose tissues, we herein analyzed its expression and
      localization in mouse livers before and after CCl(4) treatment. In
      immunohistochemical analyses, the boundary of hepatocytes provided positive
      signals for GBP28 after 3-6 h and their cytoplasm was intensely stained after 18
      h of CCl(4) treatment. Quantitative RT-PCR and in situ hybridization revealed
      that GBP28 mRNA expression was markedly elevated in CCl(4)-treated mouse livers.
      These results suggest that the circulating GBP28 binds the extracellular matrices
      of hepatocytes during the initial stage of CCl(4)-induced hepatic injury and the
      damaged hepatocytes themselves started to produce GBP28 thereafter. The induced
      expression of GBP28 was also observed in human hepatoma HepG2 cells after
      treatment with IL-6. Thus, GBP28 is also produced by the liver, where it
      undergoes tissue damage-induced transcriptional regulation.

PMID- 11444853
TI  - Characterization of human skeletal muscle Ankrd2.
AB  - Human Ankrd2 transcript encodes a 37-kDa protein that is similar to mouse Ankrd2
      recently shown to be involved in hypertrophy of skeletal muscle. These novel
      ankyrin-rich proteins are related to C-193/CARP/MARP, a cardiac protein involved
      in the control of cardiac hypertrophy. A human genomic region of 14,300 bp was
      sequenced revealing a gene organization similar to mouse Ankrd2 with nine exons,
      four of which encode ankyrin repeats. The intracellular localization of Ankrd2
      was unknown since no protein studies had been reported. In this paper we studied
      the intracellular localization of the protein and its expression on
      differentiation using polyclonal and monoclonal antibodies produced to human
      Ankrd2. In adult skeletal muscle Ankrd2 is found in slow fibers; however, not all
      of the slow fibers express Ankrd2 at the same level. This is particularly evident
      in dystrophic muscles, where the expression of Ankrd2 in slow fibers seems to be
      severely reduced.

PMID- 11444854
TI  - JDD1, a novel member of the DnaJ family, is expressed in the germinal zone of the
      rat brain.
AB  - We identified a novel gene encoding a new member of the DnaJ family, JDD1 (J
      domain of DnaJ-like-protein 1), from the rat. The cloned JDD1 cDNA is 1689 bp in
      size and its deduced amino acid sequence consists of 259 amino acid residues.
      Immunoblot analysis revealed that JDD1 protein is approximately 30 kDa in size.
      JDD1 has a J domain that is unique to the DnaJ family but lacks the G/F region (a
      region that is rich in the amino acids glycine and phenylalanine) and the zinc
      finger region (also known as the cysteine-rich region)-both characteristic to the
      DnaJ. JDD1 mRNA is expressed heterogeneously in vivo. In the central nervous
      system, JDD1 mRNA expression is confined to the germinal (ventricular and
      subventricular) zone where, except for cells situated deepest in the ventricular
      zone, neurons and glias are generated and then differentiate during the embryonic
      period. Expression of JDD1 mRNA in the subventricular zone persists after birth.
      In addition to the brain, its robust expression is notable in the liver, lung,
      cortex of the kidney, and several other tissues in the embryo.

PMID- 11444855
TI  - VLDL modulates the cytokine secretion profile to a proinflammatory pattern.
AB  - Human very-low-density lipoprotein (VLDL) inhibits DNA synthesis in lymphocytes
      activated by the nonspecific mitogen concanavalin A (Con A). We studied the
      effects of VLDL on lymphocyte activation (IL-2 receptor expression), cell cycle
      progression, and production of IL-2 and of IL-4 (a proinflammatory and an anti
      inflammatory interleukin, respectively) to understand why an atherogenic
      lipoprotein inhibits cell proliferation. After 48 h of stimulation with the
      mitogen, VLDL decreased the population of cells bearing IL-2 receptor and the
      population of T-cells that progress through the cell cycle, increasing the
      population of T-cells in G(0)/G(1). Cells cultured in the presence of Con A and
      VLDL produced higher levels of IL-2 and lower levels of IL-4 than cells cultured
      without VLDL. These results suggest that VLDL inhibits lymphocyte proliferation
      by reducing IL-2 receptor and enhancing the levels of IL-2. Probably, one
      atherogenic effect of VLDL is to modulate the cytokine secretion profile of
      lymphocytes to a predominantly proinflammatory response.

PMID- 11444856
TI  - Identification and characterization of a novel human testis-specific kinase
      substrate gene which is downregulated in testicular tumors.
AB  - By using the positional candidate gene approach, we identified a novel putative
      serine/threonine kinase substrate gene that maps to chromosome 19q13.3. Screening
      of expressed sequence tags and reverse transcription-polymerase chain reaction of
      total RNA from human tissues allowed us to establish the expression of the gene
      and delineate its genomic organization (GenBank Accession No. AF200923). This
      gene (TSKS, for testis-specific kinase substrate) is composed of 11 exons and 10
      intervening introns and is likely the human homolog of the mouse testis-specific
      serine kinase substrate gene. The predicted protein-coding region of the gene is
      1779 bp, encoding for a 592-amino-acid polypeptide with a calculated molecular
      mass of 65.1 kDa. Genomic analysis of the region 19q13.3 placed the TSKS gene
      close to the known genes IRF3, RRAS, and alpha-Adaptin A. TSKS exhibits high
      levels of expression exclusively in human testicular tissue. The expression of
      TSKS is downregulated in cancerous testicular tissue, in comparison to adjacent
      normal tissue. TSKS expression was very low or undetectable in seminoma,
      teratocarcinoma, embryonal, and Leydig cell tumors, while high expression was
      observed in testicular tissue adjacent to tumors which contain premalignant
      carcinoma in situ. The expression of the TSKS gene was very low in two human
      embryonal carcinoma cell lines, 2102Ep and NTERA-2. These observations suggest a
      role of TSKS in testicular physiology, most probably in the process of
      spermatogenesis or spermiogenesis.

PMID- 11444857
TI  - DNA mismatch repair enzyme activity and gene expression in prostate cancer.
AB  - Microsatellite instability (MSI) of short repetitive sequences in human
      chromosomal DNA can result from defective DNA mismatch repair function in tumor
      cells. We hypothesize that DNA mismatch repair (MMR) activity is down-regulated
      during prostatic carcinogenesis. To test this hypothesis, MMR activities and
      mismatch repair-related genes were analyzed in five different prostate cancer
      cell lines. Our results demonstrate that MMR activities were decreased as
      compared to MMR proficient HeLa cells. Interestingly, LNCaP, PC-3 and DU145 had
      much lower MMR activities as compared to DUPro and TSUPr1. The MMR-related genes
      (hMLH1, hPMS1, hPMS2, hMSH2, hMSH3, hMSH6) showed mRNA transcripts in all
      prostate cancer cell lines. However, Western blotting showed decreased or absent
      hMLH1 protein expression in PC-3, DU145, DUPro and TSUPr1 cells. Similarly, the
      hMSH2 protein expression was low or absent in DU145 and LNCaP cells. This is the
      first report that demonstrates decreased MMR activities is associated with low
      expression of hMLH1, hMSH2 and other MMR-related proteins in prostate cancer.

PMID- 11444858
TI  - Leukotoxicity of pyoverdin, production of reactive oxygen species, and effect of
      UV radiation.
AB  - Pyoverdin was purified by solvent extraction, gel filtration, and ionic exchange
      chromatography. Assays of cytotoxic of pyoverdin were done with human leukocytes
      and macrophages from the peritoneum of mice. Both cell quantities showed a
      significant reduction. Death was followed by lysis in a dose-dependent form. The
      mechanism of action of pyoverdin involved the stimulation of reactive oxygen
      species (ROS) measured by Nitroblue Tetrazolium (NBT) reaction and
      chemiluminescence (CL). UV radiation at 368 nm increased the leukotoxicity;
      expositions of 5 min were enough to photostimulate the effect of pyoverdin on
      cellular oxydative metabolism, which increased between 35.4 and 53.2%. Genestein,
      an inhibitor of tyrosine kinases, counteracted the ROS stimuli of pyoverdin,
      suggesting endocytic mechanism of action for this pigment. The little chloroquine
      interference on oxydative stress indicated that intraphagosomal pH and the
      stimuli of reactive nitrogen intermediaries (RNI) seem to be of less importance
      than ROS in pyoverdin action on leukocytes.

PMID- 11444859
TI  - Isolation of a novel thermolabile heterodimeric ribonuclease with antifungal and
      antiproliferative activities from roots of the sanchi ginseng Panax notoginseng.
AB  - An isolation procedure, consisting of ion exchange chromatography on CM
      Sepharose, affinity chromatography on Affi-gel blue gel, and fast protein liquid
      chromatography on Mono S, was utilized to purify a base-nonspecific,
      heterodimeric ribonuclease (RNase) with diverse activities from roots of the
      sanchi ginseng Panax notoginseng. The RNase is unique in that it consists of two
      different nonglycoprotein subunits with a molecular weight of 27 and 29 kDa,
      respectively. The latter subunit is characterized by an N-terminal sequence
      showing remarkable similarity to that of the bitter gourd RNase. The Panax
      notoginseng RNase demonstrates potent RNase and translation-inhibitory
      activities. In addition, it exhibits antiproliferative activity toward leukemia
      L1210 cells and antifungal activity against Physalospora piricola and Coprinus
      comatus. Its RNase activity is not heat-resistant, unlike most RNases which are
      thermostable.

PMID- 11444860
TI  - Peptides from pinto bean and red bean with sequence homology to cowpea 10-kDa
      protein precursor exhibit antifungal, mitogenic, and HIV-1 reverse transcriptase
      inhibitory activities.
AB  - Peptides with a molecular weight of 5 kDa have been isolated from seeds of the
      pinto bean and red bean, respectively. The peptides manifest an N-terminal
      sequence with remarkable resemblance to those of cowpea 10-kDa protein precursor
      and garden pea disease resistance response protein. The bean peptides possess
      potent antifungal activity toward a variety of fungal species including Botrytis
      cinerea, Mycosphaerella arachidicola, and Fusarium oxysporum. The proteins also
      demonstrate mitogenic activity toward mouse splenocytes and an inhibitory action
      on HIV-1 reverse transcriptase.

PMID- 11444861
TI  - Molecular characterization of the Xenopus CCAAT-enhancer binding protein beta
      gene promoter.
AB  - Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP)
      family play key roles in the regulation of genes implicated in the control of
      growth, differentiation, metabolism, and inflammation. The recent limited studies
      on the promoter regions of C/EBP genes, particularly C/EBPalpha, have indicated
      the potential existence of species-specific regulatory mechanisms. It is
      therefore essential that the promoter regions of different C/EBP genes from a
      wide range of species are investigated in detail. As an important step toward
      this goal, we report here the characterization of the Xenopus laevis C/EBPbeta
      gene promoter. Sequence analysis showed that the 1.6-kb promoter region contained
      putative binding sites for several transcription factors that have previously
      been implicated in the regulation of the C/EBPs, including C/EBP, CREB, Myb,
      STAT, and USF. The -288/+91 promoter region was capable of directing high levels
      of expression in the hepatoma Hep3B cell line. In addition, this minimal promoter
      could be autoregulated by both C/EBPalpha and C/EBPbeta and activated by
      lipopolysaccharide, interleukin-6 and CREB. These results therefore demonstrate
      that several aspects of C/EBPbeta regulation in mammals have been highly
      conserved in amphibians. However, a comparison of C/EBPbeta gene promoters
      characterized to date does indicate the existence of species-specific differences
      in autoregulation.

PMID- 11444862
TI  - Raman study of the interaction between polyamines and a GC oligonucleotide.
AB  - The interaction between the oligonucleotide d[G(CG)(7)]. d[C(GC)(7)] and the
      three biogenic polyamines putrescine, spermidine, and spermine under
      physiological conditions has been studied by Raman spectroscopy. The results
      indicate the formation of highly ordered aggregated structures in solution,
      largely stabilized by electrostatic attractions, which have been described as
      cholesteric phases. Aggregation seems to be preceded by a partial B --> Z
      conformational transition for spermidine and spermine, which would allow for a
      deeper oligonucleotide-polyamine interaction. Interaction with the nucleic bases
      has also been evidenced for aggregates. At low polyamine concentrations the
      preferential binding sites are similar to those proposed for their interactions
      with ct-DNA. With increasing the polyamine concentration, the oligonucleotide
      polyamine interactions involve both minor and major grooves, which is consistent
      with the formation of cholesteric phases.

PMID- 11444863
TI  - Enolase, a cellular glycolytic enzyme, is required for efficient transcription of
      Sendai virus genome.
AB  - Cellular proteins (host factors) may play key roles in transcription of Sendai
      virus (SeV) genome. We have previously shown that the host factor activity, which
      stimulates in vitro mRNA synthesis of SeV, from bovine brain comprises at least
      three complementary factors, and two of them were identified as tubulin and
      phosphoglycerate kinase (PGK). Here the third host factor activity was further
      resolved into two complementary factors, and one of them was purified to an
      almost single polypeptide chain with an apparent M(r) of 52,000 (p52) and was
      identified as a glycolytic enzyme, enolase. Recombinant human alpha-enolase, as
      did p52, acted synergistically with other three host factors to stimulate SeV
      mRNA synthesis. West-Western blot analysis demonstrated that tubulin specifically
      binds enolase as well as PGK, suggesting that these two glycolytic enzymes
      regulate SeV transcription through their interactions with tubulin.

PMID- 11444864
TI  - YfiD of Escherichia coli and Y06I of bacteriophage T4 as autonomous glycyl
      radical cofactors reconstituting the catalytic center of oxygen-fragmented
      pyruvate formate-lyase.
AB  - Reaction of oxygen with the glycyl radical in pyruvate formate-lyase (PFL) leads
      to cleavage of the polypeptide backbone between N-Calpha of Gly734. A recombinant
      protein comprising the core of PFL (Ser1-Ser733) is shown here to associate with
      the YfiD protein (14 kDa) of Escherichia coli and likewise with the homologous T4
      encoded Y06I protein, yielding upon reaction with PFL activase a heterooligomeric
      PFL enzyme that has full catalytic activity (35 U/nmol). Treatment of the
      activated complexes with oxygen led to cleavage of the 14 kDa proteins into 11
      and 3 kDa polypeptides as expected for the localization of the putative glycyl
      radical at Gly102 (YfiD) or Gly95 (Y06I). For the isolated fragments from Y06I,
      mass spectrometric analysis (nanoESI-MS) determined a C-terminal serine
      carboxamide in the 11 kDa fragment, and a N-terminal oxalyl modification in the 3
      kDa fragment. We speculate that YfiD in E. coli and other facultative anaerobic
      bacteria has evolved as a "spare part" for PFL's glycyl radical domain, utilized
      for rapid recovery of PFL activity (and thus ATP generation) in cells that have
      experienced oxidative stress.

PMID- 11444865
TI  - Application of different surface plasmon resonance biosensor chips to monitor the
      interaction of the CaM-binding site of nitric oxide synthase I and calmodulin.
AB  - Surface plasmon resonance biosensors depend on modified gold surfaces to allow
      immobilization of proteins or peptides for interaction analysis. We investigated
      sensor chip surfaces that differ in the geometry of the immobilization matrix:
      two contain a three-dimensional coupling matrix and two have a surface with
      immobilization sites on a two-dimensional plane. Properties of sensor chips were
      compared by studying the interaction of calmodulin with a peptide representing
      the calmodulin-binding site of nitric oxide synthase I. Apparent K(D) values were
      determined by three different procedures in order to apply tests for self
      consistency. At low surface densities (5-8 fmol/mm(2)) on three of the four
      tested surfaces, estimated K(D) values were within one order of magnitude and
      similar to the value found in solution (K(D) = 1-3 nM). When immobilization
      densities were increased by one to two orders of magnitude, apparent association
      rate constants were less distorted on a flat carboxymethylated surface than on
      dextran-coated sensor chips.

PMID- 11444866
TI  - Effect of selenium and vitamin E deficiency on differential gene expression in
      rat liver.
AB  - To examine the molecular events associated with selenium (Se) and vitamin E (VE)
      deficiency, we applied cDNA array technology to define the transcriptional
      response in the liver of Se- and VE-deficient rats. VE deficiency alone did not
      induce any significant changes in expression profile among the genes evaluated.
      Se deficiency lead to a down-regulation of Se-dependent cGPx and to an induction
      of genes, encoding for detoxifying enzymes in liver (cytochrome P450 4B1, UDP
      glucuronosyltransferase 1). Combined VE and Se deficiency was characterized by
      alterations in the expression level of genes encoding for proteins involved in
      inflammation (multispecific organic anion exporter, SPI-3 serine protease
      inhibitor) and acute phase response (alpha-1 acid glycoprotein, metallothionein
      1). Additionally, a significant down-regulation in the expression level of genes
      important in the inhibition of apoptosis (defender against cell death 1 protein,
      Bcl2-L1), cell cycle (G1/S-specific cyclin D1) and antioxidant defense (gamma
      glutamylcysteine synthetase catalytic subunit) was demonstrated. The experimental
      strategy identified several novel Se and VE sensitive genes.

PMID- 11444867
TI  - Cloning and analysis of the rat glutamate-cysteine ligase modifier subunit
      promoter.
AB  - Glutamate-cysteine ligase (GCL), the rate-limiting enzyme in glutathione (GSH)
      synthesis, is made up of two subunits, a catalytic (GCLC) and a modifier (GCLM)
      subunit, which are differentially regulated. Increased GCLM expression occurs
      under certain oxidative stress conditions. To facilitate studies of GCLM
      transcriptional regulation, we have cloned and characterized a 1.86-kb 5'
      flanking region of the rat GCLM (GenBank Accession No. AF311745). A TATA-like
      element and one transcriptional start sites are located at 364 and 93 nucleotides
      upstream of the translational start site, respectively. The promoter contains
      consensus binding sites for many transcription factors including activator
      protein 1 (AP-1), transcription factor 11 (TCF11), heat shock transcription
      factor (HSF), and nuclear factor kappa B (NFkappaB). The rat GCLM promoter was
      able to drive efficiently luciferase expression in H4IIE cells. Sequential
      deletion analysis revealed DNA regions, -649 to -154 and -1251 to -649, are
      involved in positive and negative gene regulation, respectively. Candidate
      transcription factors were identified by DNase I footprinting.

PMID- 11444868
TI  - The antitumor somatostatin analogue TT-232 induces cell cycle arrest through
      PKCdelta and c-Src.
AB  - The heptapeptide TT-232 is structurally related to the hypothalamic hormone
      somatostatin and shows promise as an anticancer drug because of its tumor
      specific cytotoxic effects. Apart from the ability to induce apoptosis, the
      synthetic peptide can trigger an alternative pathway that leads to cell cycle
      arrest in certain tumor cell systems. We found that pulse treatment with TT-232
      blocks the cell cycle G(1)/S transition irreversibly in A431 cells. Investigation
      of the TT-232 signaling pathway yielded results similar to those reported for
      somatostatin although its affinity to the somatostatin receptor 1 is
      significantly reduced. We show that functional protein kinase C (PKC) delta as
      well as c-Src are necessary mediators of the TT-232 cytostatic effect and we
      propose a signaling pathway that leads to cell cycle arrest.

PMID- 11444869
TI  - Localization of N-terminal sequences in human AMP deaminase isoforms that
      influence contractile protein binding.
AB  - The reversible association of AMP deaminase (AMPD, EC 3.5.4.6) with elements of
      the contractile apparatus is an identified mechanism of enzyme regulation in
      mammalian skeletal muscle. All three members of the human AMPD multigene family
      contain coding information for polypeptides with divergent N-terminal and
      conserved C-terminal domains. In this study, serial N-terminal deletion mutants
      of up to 111 (AMPD1), 214 (AMPD2), and 126 (AMPD3) residues have been constructed
      without significant alteration of catalytic function or protein solubility. The
      entire sets of active enzymes are used to extend our understanding of the
      contractile protein binding of AMPD. Analysis of the most truncated active
      enzymes demonstrates that all three isoforms can associate with skeletal muscle
      actomyosin and suggests that a primary binding domain is located within the C
      terminal 635-640 residues of each polypeptide. However, discrete stretches of N
      terminal sequence alter this behavior. Residues 54-83 in the AMPD1 polypeptide
      contribute to a high actomyosin binding capacity of both isoform M spliceoforms,
      although the exon 2- enzyme exhibits significantly greater association compared
      to its exon 2+ counterpart. Conversely, residues 129-183 in the AMPD2 polypeptide
      reduce actomyosin binding of isoform L. In addition, residues 1-48 in the AMPD3
      polypeptide dramatically suppress contractile protein binding of isoform E, thus
      allowing this enzyme to participate in other intracellular interactions.

PMID- 11444870
TI  - Identification of the gene encoding NADH-rubredoxin oxidoreductase in Clostridium
      acetobutylicum.
AB  - NADH-rubredoxin oxidoreductase (NROR), a flavoprotein from the obligately
      anaerobe Clostridium acetobutylicum is encoded by an ORF (nror) of 1140
      nucleotides. Whereas primary structure analysis reveals that NROR has amino acid
      sequence patterns homologous with those involved in FAD and NAD-binding, the
      enzyme is distantly related to other flavoproteins in the databank. NROR is
      highly active for reducing clostridial rubredoxin (Rd) especially against C.
      acetobutylicum Rd with an efficiency (k(cat)/K(m)) of 400,000 mM(-1)s(-1). These
      results suggest that Rd from C. acetobutylicum, C. pasteurianum, C. butyricum,
      and C. cellulolyticum can be interchanged with each other. Since C.
      acetobutylicum is the sole Clostridium strain that possesses such an enzyme,
      possible functions are discussed with regard to Desulfovibrio gigas and
      Pyrococcus furiosus, the only two other anaerobic systems for which a similar
      activity was reported, but no gene isolated.

PMID- 11444871
TI  - Alterations of load-induced p38 MAP kinase activation in failing rat hearts.
AB  - Hemodynamic load-induced cardiac p38 mitogen-activated protein kinase (MAPK)
      activation was studied in normotensive control Dahl rats (n = 10) and
      hypertensive Dahl rats with heart failure (n = 16). The isolated heart from each
      animal was stretched on a Langendorff apparatus at an equivalent diastolic wall
      stress, and the p38-MAPK activity of the left ventricular (LV) myocardium was
      analyzed by immunoprecipitation-kinase assay. Compared to the control hearts, the
      stretch-induced p38-MAPK activities were significantly decreased, and inversely
      correlated with the LV diameter (r = -0.73, P < 0.01). Chronic treatment with an
      angiotensin II AT1-receptor antagonist, valsartan (10 mg/kg/day), ameliorated
      cardiac function and remodeling process in the failing hearts, which was
      associated with an improvement of the p38-MAPK activities. Thus, the mechano
      signal transduction of p38-MAPK pathway is downregulated in the failing hearts,
      along with progressive ventricular remodeling. The data also suggest that the
      beneficial effects of the AT1-receptor antagonists are potentially mediated by
      the restoration of cardiac growth-related signal transduction.

PMID- 11444872
TI  - Introduction of tapasin gene restores surface expression of HLA class I
      molecules, but not antigen presentation of an HIV envelope peptide in a hepatoma
      cell line.
AB  - A hepatoma cell line, Hep G2, reveals the diminished HLA class I surface
      expression and the reduced expression of LMP2, LMP7, and tapasin transcripts,
      suggesting that the reduced expression of these transcripts may be associated
      with the low expression of HLA class I molecules. Introduction of tapasin gene
      dramatically up-regulates the surface expression of HLA class I molecules on Hep
      G2 cells, and unexpectedly, enhances the expression of LMP2 and LMP7 transcripts
      as well. Unlike Hep G2, these tapasin-transfected Hep G2 cells are recognized by
      allo-specific CTL. However, the transfectant is unable to endogenously present an
      HIV envelope peptide to an HIV-specific CTL clone, suggesting that a proteasome
      independent antigen processing pathway exists and still remains defective in the
      transfectant. These data may provide significant evidence that the nonproteasomal
      antigen processing pathway as well as the proteasomal pathway may be impaired in
      tumor cells to escape immune surveillance performed by CTL.

PMID- 11444873
TI  - Constitutive IFN-alpha/beta signal for efficient IFN-alpha/beta gene induction by
      virus.
AB  - Efficient IFN-alpha/beta gene induction in virus-infected cells is an event
      central to innate immunity, in which the transcription factor IRF-7 plays a
      critical role together with IRF-3. Unlike IRF-3, IRF-7 is short-lived and its
      gene expression is dependent on IFN-alpha/beta signalling; hence, the signal
      dependent enhancement of IRF-7 gene induction during viral infection is essential
      for positive-feedback regulation of IFN-alpha/beta gene induction. Here, we
      provide evidence that constitutive, IRF-3/IRF-7-independent production of IFN
      alpha/beta in uninfected cells is critical for setting the IRF-7 expression
      levels, determining whether or not the positive-feedback mechanism will operate
      effectively upon viral infection. In fact, spleen cells are more dependent than
      fibroblasts on this mechanism; the IFN-alpha/beta gene induction is impaired more
      severely by blocking the IRF-7 induction pathway than by introducing an IRF-3
      null mutation. Thus, the constitutive IFN-alpha/beta signal provides a foundation
      for the IRF-7-mediated enhancement of its own production in response to virus
      infection.

PMID- 11444874
TI  - Kinetic mechanism and identification of the active site tyrosine residue in
      Enterobacter amnigenus arylsulfate sulfotransferase.
AB  - Bacterial arylsulfate sulfotransferase (ASST) catalyzes the transfer of a sulfate
      group from a phenyl sulfate ester to a phenolic acceptor. The kinetic mechanism
      of Enterobacter amnigenus ASST was determined. Plots of 1/v versus 1/[substrate
      (A)] at different fixed substrate (B) concentrations gave a series of parallel
      lines. One of the reaction products, p-nitrophenol, inhibited the enzyme
      noncompetitively with respect to p-nitrophenyl sulfate, but competitively to
      alpha-naphthol. These results correspond to a ping pong bi bi mechanism. By site
      directed mutagenesis, we substituted each conserved tyrosine residue with
      phenylalanine. Among the mutants, Y123F showed severely reduced catalytic
      activity. We conclude that Tyr 123 is an essential active site residue. A
      mechanistic hypothesis is presented to account for these observations.

PMID- 11444875
TI  - Differential virulence-gene mRNA expression in coccoid forms of Helicobacter
      pylori.
AB  - Controversy exists whether coccoid forms of Helicobacter pylori maintain
      transcriptional and translational processes. The aim of the present study was to
      investigate mRNA levels in coccoid H. pylori and, if possible, to establish a
      correlation with the state of nonrandom fragmentation of rRNA in those cells. For
      that purpose, UreA, UreI, CagA, VacA, SodB, and Hsp60 mRNA levels in bacillary
      and coccoid forms of H. pylori CCUG 17874(T), H. pylori 26695, and H. pylori J99,
      respectively, were studied by means of a multiplex reverse-transcription PCR
      assay and Southern blot analysis of the RT-PCR-amplified products. Nonrandom
      fragmentation of 23S rRNA was assessed by a recently described assay. Virulence
      gene-derived mRNA transcripts were visualized in DNase I-treated RNA
      preparations. All three strains revealed the presence of different mRNA patterns
      in bacillary and coccoid forms. Putative promoter sequences similar to the
      consensus Escherichia coli -10 hexamer TATAAA box were present in all six
      virulence genes analyzed. Moreover, the decrease seen in mRNA levels during
      conversion into the coccoid form appeared to correlate with the 23S rRNA
      nonrandom fragmentation pattern. The present data indicate that modulation of
      virulence-gene expression is differently regulated in bacillary and coccoid H.
      pylori.

PMID- 11444876
TI  - Carnitine palmitoyl transferase I and the control of beta-oxidation in heart
      mitochondria.
AB  - Mitochondrial beta-oxidation provides much of the fuel requirements of heart and
      skeletal muscle despite the malonyl-CoA concentration greatly exceeding the
      IC(50) of carnitine palmitoyl transferase for malonyl-CoA. To try to explore the
      relationship between inhibition of carnitine palmitoyl transferase I activity and
      beta-oxidation flux, we measured the flux control coefficient of carnitine
      palmitoyl transferase I over beta-oxidation carbon flux in suckling rat heart
      mitochondria. The flux control coefficient was found to be 0.08 +/- 0.05 and 50%
      of carnitine palmitoyl transferase I activity could be inhibited before beta
      oxidation flux was affected. These observations may help to explain the presence
      of high rates of beta-oxidation despite the high concentration of malonyl-CoA in
      rat heart; we hypothesize that although not rate-limiting in vitro, carnitine
      palmitoyl transferase is rate-limiting in vivo because of the high malonyl-CoA
      concentration in heart and muscle.

PMID- 11444877
TI  - A novel human homologue of the SH3BGR gene encodes a small protein similar to
      Glutaredoxin 1 of Escherichia coli.
AB  - Glutaredoxins (GRXs) are ubiquitous GSH-dependent oxidoreductases, which catalyze
      the reduction of protein-glutathionyl-mixed disulfides and are considered to play
      an important role in the enzymatic regulation of redox-sensitive proteins. In
      this paper, we describe the identification and characterization of a new human
      homologue of the SH3BGR gene, named SH3BGRL3 (SH3 domain binding glutamic acid
      rich protein like 3). SH3BGRL3 is widely expressed and codes for a highly
      conserved small protein, which shows a significant similarity to Glutaredoxin 1
      (GRX1) of Escherichia coli and is predicted to belong to the Thioredoxin
      Superfamily. However, the SH3BGRL3 protein lacks both the conserved cysteine
      residues, which characterize the enzymatic active site of GRX. This structural
      feature raises the possibility that SH3BGRL3 could function as an endogenous
      modulator of GRX biological activity. EGFP-SH3BGRL3 fusion protein expressed in
      COS-7 cells localizes both to the nucleus and to the cytoplasm. The SH3BGRL3 gene
      was mapped to chromosome 1p34.3-35.

PMID- 11444878
TI  - Impaired vitamin A-mediated mucosal IgA response in IL-5 receptor-knockout mice.
AB  - To clarify actions of vitamin A on mucosal immunity associated with interleukin-5
      (IL-5), we examined effects of vitamin A on mucosal IgA level in IL-5 receptor
      alpha-chain-knockout (IL-5Ralpha(-/-)) mice. Daily supplementation of retinyl
      acetate (1 mg/mouse) increased Th2 cytokine levels and a number of their positive
      cells in the small intestinal mucosa of IL-5Ralpha(-/-) mice, as observed in wild
      type or IL-5Ralpha(+/-) mice. Wild-type and heterozygous mice increased the IgA
      level and a number of IgA-containing cells in the mucosa in response to the
      vitamin A treatment, but not in IL-5Ralpha(-/-) mice. Retinyl acetate increased
      anti-cholera toxin (CT) IgA level in the mucosa of wild-type mice, improving
      their survival rate after an exposure to 0.4 mg of CT. However, retinyl acetate
      failed to induce resistance to CT toxicity in IL-5Ralpha(-/-) mice. Our results
      suggest that IL-5 may play an important role in an action of vitamin A on mucosal
      IgA system.

PMID- 11444879
TI  - Effect of two polyamine toxins on the bacterial porin OmpF.
AB  - Spermine, a polyamine based on a 12-carbon motif, is an effective inhibitor of E.
      coli OmpF porin. Here we study the inhibition of porin by two polyamine toxins
      commonly used as modulators of polyamine-sensitive channels: Philanthotoxin-433
      (PhTX) from wasp venom and Joro spider toxin (JSTX). Both are highly asymmetric
      molecules, with at one end a 12-carbon chain polyamine targeting the molecule to
      the porin constriction zone, and at the other end large aromatic groups
      conferring to this extremity a size in the order of the OmpF constriction zone.
      Here we report that PhTX, but not Joro toxin, induces a high degree of flickering
      in the OmpF-mediated current. The effect is concentration and voltage-dependent,
      and greatly diminished in a mutant lacking D113 on the constriction loop, a
      residue previously shown to be required for spermine sensitivity. Possible
      reasons for the distinct sensitivity of OmpF to PhTX and Joro toxin are
      discussed.

PMID- 11444880
TI  - Sites on FIP-3 (NEMO/IKKgamma) essential for its phosphorylation and NF-kappaB
      modulating activity.
AB  - FIP-3 (NEMO/IKKgamma) is an essential modulator of the activity of NF-kappaB by
      mechanisms that include alterations in the phosphorylation, ubiquination, and
      degradation of IkappaBalpha. The multiple protein-protein interactions of FIP-3
      (NEMO/IKKgamma) in a high molecular weight IKK complex indicated that this
      protein may be a link between some of the receptor-proximal upstream signal
      transduction molecules such as RIP and the downstream effects on IkappaBalpha.
      Although FIP-3 (NEMO/IKKgamma) has no intrinsic kinase activity, it has been
      shown to increase the kinase activity of IKKbeta. In this manuscript, the results
      of serine to alanine mutations at five sites on FIP-3 (NEMO/IKKgamma) are
      described, and functional assays demonstrated that two of these mutants affect
      both the phosphorylation and kinase activity of IKKbeta. Protein kinase Calpha
      appeared to be the kinase that was required for the posttranslational
      modification of FIP-3 (NEMO/IKKgamma). One of the serine targets of the protein
      kinase Calpha enzyme at amino acid 141 was within a leucine zipper-like sequence
      of FIP-3 (NEMO/IKKgamma), which might affect its interactions with other proteins
      on the signal transduction pathway. The second serine, which augmented the
      inhibition, was at amino acid 85 within the FIP-3 (NEMO/IKKgamma) interaction
      site with IKKbeta. When both serines were mutated simultaneously, the effect on
      IKKbeta and IkappaBalpha phosphorylation was more profoundly affected.

PMID- 11444881
TI  - Insulin resistance and type 2 diabetes are not related to resistin expression in
      human fat cells or skeletal muscle.
AB  - Resistin is secreted by rodent fat cells and was recently postulated to be an
      important link between obesity and insulin resistance. We examined Resistin gene
      expression with real-time RT-PCR in human isolated fat cells, adipose tissue, and
      muscle from 42 individuals of varying degrees of overweight and who had normal
      insulin sensitivity or were insulin-resistant or Type 2 diabetic. Resistin was
      not expressed in human muscle nor was it expressed in most human isolated fat
      cells or intact biopsies. No difference was found between normal, insulin
      resistant, or Type 2 diabetic samples. However, a very low but specific Resistin
      expression could be demonstrated in isolated fat cells and intact adipose tissue
      from some individuals (n = 3 and n = 4, respectively). There was no evidence for
      the expression of splice variants in the human samples. Thus, Resistin does not
      seem to be an important link to insulin resistance and Type 2 diabetes in human.

PMID- 11444882
TI  - Gene expression profiling of an arteriogenic impotence model.
AB  - Penile arterial insufficiency is one of the most common causes of ED. We have
      established a traumatic arteriogenic insufficiency rat model by the ligation of
      the pudendal arteries. To simulate both acute and chronic traumatic injuries,
      five ligation periods (6 h, 3 days, 7 days, 3 weeks, and 6 weeks) were chosen. By
      electrostimulation of the cavernous nerve, the intracavernous pressure was
      determined to be between 20 and 40-cm H(2)O for the ligated rats compared to
      around 100-cm H(2)O for the control rats. The erectile tissue in the corpus
      cavernosum of these rats was then subjected to microarray analysis, in which an
      array that contains cDNA fragments representing 1176 rat genes was used. The
      results demonstrated that normal rat corpus cavernosum expressed approximately
      200 genes at detectable levels and that ligation produced differential expression
      of approximately 25 genes, depending on the duration of ligation. The most highly
      ligation-induced gene was apolipoprotein D (ApoD), with peak expression in the 3-
      and 7-day ligated rats. Three of the insulin-like growth factor binding proteins
      (IGFBP-1, 3, and 5) were upregulated in all ligated rats. IGFBP-6, which was one
      of the most highly expressed genes in the normal corpus cavernosum, was down
      regulated in all ligated rats. Cysteine proteases of the cathepsin family were
      also differentially expressed between control and ligated rats, with cathepsin K
      being down-regulated most. A few genes were upregulated only in the 6-week
      ligated rats, including angiotensin-converting enzyme. Finally, VEGF, whose
      induction has been identified in many other ischemic tissues, was not induced in
      corpus cavernous tissue of ligated rats.

PMID- 11444883
TI  - Quality criticism required.

PMID- 11444884
TI  - Aromatherapy: a survey of current practice in the management of rheumatic disease
      symptoms.

PMID- 11444885
TI  - Analgesic effectiveness of subcutaneous carbon-dioxide insufflations as an
      adjunct treatment in patients with non-specific neck or low back pain.
AB  - OBJECTIVES: To evaluate the analgesic effectiveness of subcutaneous carbon
      dioxide insufflations in addition to standard physical treatment in patients with
      non-specific neck or low back pain. DESIGN: A pragmatic, randomized controlled
      trial. SETTING: Rehabilitation hospital inpatients. INTERVENTIONS: Patients
      received either subcutaneous carbon-dioxide insufflations (10 treatments) and
      standard physical treatment or standard physical treatment only. OUTCOME
      MEASURES: Affective pain perception (42-point scale), sensory pain perception (30
      point scale), pain intensity (100 mm visual analogue scale). RESULTS: Between
      groups differences were -2.2 [95% CI -5.2; +0.9] (affective pain perception), 
      1.2 [-3, 0; + 0.7] (sensory pain perception), and -6.5 [-14; +1.0] (pain
      intensity) respectively in favour of subcutaneous carbon-dioxide insufflations.
      CONCLUSIONS: Subcutaneous carbon-dioxide insufflations do not seem to be a
      worthwhile adjunct in the given setting of inpatient rehabilitation. Trials in a
      monotherapeutic setting, which aim more at the efficacy of subcutaneous carbon
      dioxide insufflations, might help to solve this issue.

PMID- 11444886
TI  - Is there an effect of acupuncture on the resting EEG?
AB  - OBJECTIVE: To investigate if acupuncture has a measurable effect on the resting
      electron EEG. SUBJECTS: 14 healthy volunteers with no neurological condition took
      part in the study. METHODS: Using a digital storage EEG recorder and quantitative
      frequency analysis techniques data were obtained before, during and after
      acupuncture stimulation. To minimize the effect of artefacts all data were
      collected with the subject alert, but with eyes closed. Manual stimulation of the
      LI 4 acupuncture site was undertaken for periods of 0.5, 1.0 and 2.0 min.
      Frequency analysis of the EEG data from each acupuncture event was compared to
      the baseline data to show any significant changes over the bandwidth 0.3 to 30
      Hz. Only changes greater than 2 standard deviations were considered significant.
      RESULTS: In 10 subjects the frequency spectra remained unchanged during
      acupuncture, but in three significant increases were recorded in the amplitude of
      very low frequencies between 0.5 and 2 Hz and in one subject there was an
      increase in the amplitude of the alpha band during acupuncture. All spectra
      returned to their baseline values immediately after acupuncture. OUTCOME: The
      changes recorded in the delta band of individuals during acupuncture were large
      but highly variable. They arose at a frequency that is on the limit of the
      recording equipment and where recording and physiological artefacts are known to
      occur, although there was no evidence of artefactual contamination of the data.
      The one case in which there was an increase in the alpha band is attributed to
      suppression of the dominant rhythm initially brought about by anxiety concerning
      the procedure which subsequently disappeared during acupuncture as the subject
      relaxed. CONCLUSION: It is clear that there are no changes brought about by
      acupuncture in the resting EEG in the frequency range 2-30 Hz and no evidence to
      attribute changes below 2Hz to a direct affect of acupuncture.

PMID- 11444887
TI  - Non-specific effects of traditional Chinese acupuncture in osteoarthritis of the
      hip.
AB  - OBJECTIVES: The effectiveness of acupuncture treatment in patients with
      osteoarthritis of the hip was tested. DESIGN: This is a prospective, randomized,
      controlled, patient- and investigator-blinded clinical trial. PATIENTS AND
      SETTING: The study was performed at a university department for physical medicine
      and rehabilitation. Sixty-seven patients were separated into two treatment
      groups. INTERVENTIONS: Group 1 (treatment) had traditional needle placement and
      manipulation, whereas in group 2 (control) needles were placed away from classic
      positions and not manipulated. In both groups needles were placed within the L2
      to L5 dermatomes. Outcome parameters were: pain (VAS), functional impairment (hip
      score), activity in daily life (ADL) and overall satisfaction before treatment,
      and 2 weeks and 2 months after treatment. RESULTS: For all parameters there was a
      significant improvement versus baseline in both groups 2 weeks and 2 months
      following treatment, but no significant difference between the two treatment
      groups. CONCLUSIONS: We conclude from these results that needle placement in the
      area of the affected hip is associated with improvement in the symptoms of
      osteoarthritis. It appears to be less important to follow the rules of
      traditional acupuncture techniques.

PMID- 11444888
TI  - Effects of acupuncture on skin temperature in children with neurological
      disorders and cold feet: an exploratory study.
AB  - In a single subject design, acupuncture effects on peripheral skin temperature
      were studied in six children with cold feet associated with cerebral palsy,
      progressive encephalopathy or Smith-Lemli-Opitz syndrome. Skin temperature was
      measured at fixed points on the forehead, suprasternal fossa, hand dorsum and
      palm, foot dorsum and sole from a distance of 3 cm with a Raytek Raynger ST2L.
      Acupuncture needles were inserted in arms or legs with or without electrical
      stimulation. Three children displayed a brief rise in temperature in the hands
      and one in the feet. A tendency towards a cumulative effect in improved skin
      temperature occurred in two of three children receiving additional sessions. One
      child did not respond to acupuncture. It is possible that acupuncture may
      increase skin temperature in some children with cold extremities of neurological
      origin. Studies in larger groups are needed.

PMID- 11444889
TI  - Systematic review of adverse events following acupuncture: the Japanese
      literature.
AB  - CONTEXT: Many Japanese cases of adverse events after acupuncture are not listed
      in medical databases such as Medline. Therefore, they are not easily accessible
      to researchers outside Japan. OBJECTIVE: To complement existing reviews of
      adverse events after acupuncture in the West and to provide more detailed
      discussion and analysis. DATA SOURCES: Literature search using 'Igaku Chuo Zasshi
      (Japana Centra Revuo Medicina) CD-ROM version' covering the period of 1987-1999.
      STUDY SELECTION: Case reports of adverse events, which were suspected to be due
      to acupuncture treatment, were included. Experimental studies, surveys, and news
      articles were excluded. DATA EXTRACTION: Two independent reviewers extracted data
      from located articles in a pre-defined structured way, and assessed likelihood of
      causality in each individual case. DATA SYNTHESIS: 89 articles which reported 124
      cases were located. The most frequent adverse events were: pneumothorax (25
      cases), spinal cord injury (18 cases), acute hepatitis B (11 cases), and
      localized argyria (10 cases). There were two fatalities from infections. Forty
      eight events were caused by needle breakage including 26 cases of intentionally
      embedded needle and 16 cases of accidental breakage. There were also 10 cases of
      injury from self-treatment. CONCLUSION: Although it has already been demonstrated
      that severe adverse events seem to be uncommon in standard practice, many serious
      cases of negligence have been found in the present review, suggesting that
      training system for acupuncturists (including medical doctors) should be improved
      and that unsupervised self-treatment should be discouraged.

PMID- 11444890
TI  - Alternative, complementary or concurrent health care? A critical analysis of the
      use of the concept of complementary therapy.
AB  - In this paper I critically address what is becoming the wholesale adoption of the
      concept of complementary medicine in researchers' analyses of lay participation
      in alternative therapies. This paper emerged out of a qualitative study of 21
      Canadians who use and/or practice alternative therapies. I found that only seven
      informants used the term 'complementary' in describing their use of alternative
      therapies. Of those seven who did, five were alternative practitioners. I discuss
      the variability of meaning of the concept of 'complementary' and I argue that
      alternative practitioners have a professional interest in using the concept to
      avoid seeming in competition with medical professionals and to reduce the
      likelihood of being labelled 'quacks'. I conclude with a plea for researchers to
      define their terms in analyses of individuals' use of alternative and/or their
      dual use of alternative and allopathic health care.

PMID- 11444891
TI  - The case for uncontrolled clinical trials: a starting point for the evidence base
      for CAM.
AB  - Clinical research into the effectiveness of any therapy usually progresses in a
      series of steps that are aimed at providing evidence that will lead to improved
      patient care. One important early step is the uncontrolled trial. Uncontrolled
      trials serve several crucial purposes, including establishing firmly that there
      is a clinical effect worth investigating, identifying the most suitable patients
      and the most appropriate treatments, and providing information on how large the
      effect might be. They can be conducted relatively easily by practitioners in the
      course of their normal work, and are an excellent first step for anyone
      interested in clinical research. Such studies are not only satisfying, but
      develop skills in searching the literature and writing protocols, and promote
      rigorous thinking and attention to detail. The ultimate purpose of uncontrolled
      trials is to facilitate subsequent definitive studies that will help define the
      place of CAM in health care.

PMID- 11444896
TI  - Regulating the practice of CAM--the view from the Web.

PMID- 11444897
TI  - Workshop report "Acupuncture and science: fundamental contradiction or creative
      tension" March 5(th)2001.

PMID- 11444898
TI  - Integrated Medicine Conference: can alternative medicine be integrated into
      mainstream care? London, UK 23-24th January 2001.

PMID- 11444899
TI  - Meeting the challenge: life after the Lords' report organized by the Foundation
      for Integrated Medicine.

PMID- 11444900
TI  - The general practitioners' complementary medicine versus evidence-based medicine.

PMID- 11444901
TI  - Using the Web to find information on complementary and alternative medicine.

PMID- 11444904
TI  - Involvement of proteasomes in gene induction by interferon and double-stranded
      RNA.
AB  - Cytokine induced gene expression is mediated through the ligand-dependent
      activation of the janus kinase (jak)/signal transducer and activator of
      transcription (STAT) signal transduction pathway. The ubiquitin proteasome
      pathway functions in the controlled degradation of cellular proteins, and
      regulates cytokine signal transduction through the degradation of specific
      signaling components. Interferon (IFN) treatment induces genes that function in
      ubiquitin conjugation, suggesting a reciprocal regulation of proteasome activity
      and IFN action; however, a role for the proteasome in IFN-alpha-induced gene
      expression has not been examined. In this report, we find that proteasome
      inhibitors markedly reduce the induction of interferon-stimulated-gene 15
      (ISG15), ISG43, and STAT1 by IFN-alpha and double-stranded RNA (dsRNA). The
      reduction in gene expression by proteasome inhibitors was dose-dependent, and was
      specific for ISGs. Neither STAT1 phosphorylation nor ISGF-3 activation was
      affected by proteasome inhibition at early times post-IFN treatment.
      Cycloheximide treatment diminished the effect of proteasome inhibitors on ISG
      induction, implicating an IFN/dsRNA-induced protein in this activity. These
      findings demonstrate that a functional proteasome is required for optimal ISG
      induction, and are consistent with a model in which IFN and dsRNA induce a
      proteasome-sensitive repressor of ISG expression.

PMID- 11444905
TI  - Developmental expression of two CXC chemokines, MIP-2 and KC, and their
      receptors.
AB  - CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and KC, (a cloning
      designation based on ordinate and abscissa position) as well as the CXC chemokine
      receptor, CXCR2, are expressed in a variety of cells and tissues in adult mice.
      Targeted deletion of the gene encoding murine CXCR2 does not result in obvious
      changes in the development of the organ system of the mouse, though the CXCR2-/-
      mouse is compromised with regard to its ability to resist infection, heal wounds,
      and maintain homeostasis when challenged with microbes and/or chemicals. In an
      attempt to develop insight into additional possible subtle roles of CXCR2 and its
      ligands in the development of the mouse, we examined the expression of MIP-2, KC,
      CXCR2, as well as the Duffy antigen binding protein for chemokines during
      embryonic (p.c.) days 11.5 through 14.5 in the mouse. We observed strong
      correlation between the expression of MIP-2 and CXCR2 in the developing brain,
      cardiovascular system and condensing mesenchyme between 11.5 and 13.5 days.
      Moreover, the expression of KC was parallel to the expression of the Duffy
      antigen binding protein for chemokines with regard to temporal pattern and tissue
      localization. MIP-2 and CXCR2 are highly expressed in the brain, first in the
      cerebellum and in the head mesenchyme, the meninges and the floor plate, and by
      14.5 days are also present in the telencephalon, thalamus and hypothalamus. In
      the developing brain KC and Duffy were prominently expressed in the neuronal
      tracts, the forebrain, sympathetic ganglia, and along the periphery of the neural
      tube. However, KC and Duffy were less prevalent in the developing cardiovascular
      system, lung and other organs, muscle and bone, than are CXCR2 and MIP-2. These
      data suggest that the roles for these chemokines and their receptors during
      development may be more significant than was initially thought based upon the
      phenotype of the mice with targeted deletion of CXCR2 and Duffy.

PMID- 11444906
TI  - Astrocyte differentiation of fetal neuroepithelial cells involving cardiotrophin
      1-induced activation of STAT3.
AB  - Cardiotrophin-1 (CT-1) belongs to the interleukin (IL-)6 family of cytokines that
      share membrane glycoprotein 130 (gp130) as a receptor component critical for
      signal transduction. We here observed that CT-1 was expressed in mouse fetal
      neuroepithelial cells, and was capable of inducing astrocyte differentiation from
      these cells in a synergistic manner with bone morphogenetic protein (BMP)-2,
      whose expression was also found in the fetal brain. CT-1-induced astrocyte
      differentiation was solely gp130-dependent. CT-1-stimulation led to promoter
      activation of the gene for an astrocyte marker, glial fibrillary acidic protein
      (GFAP), which was clearly inhibited by expression of a dominant negative form of
      a gp130-downstream transcription factor, signal transducer and activator of
      transcription 3(STAT3), or by introduction of a mutation in a single STAT3
      binding site in the promoter, suggesting a critical role of STAT3 in the CT-1
      induced GFAP transcription. These results suggest that astrocyte differentiation
      in the developing brain involves CT-1-signaling which cooperates with BMP2.

PMID- 11444907
TI  - IFN-beta inhibits the ability of T lymphocytes to induce TNF-alpha and IL-1beta
      production in monocytes upon direct cell-cell contact.
AB  - Tumour necrosis factor (TNF)-alpha and interleukin (IL-)1beta, essential players
      in the pathogenesis of immuno-inflammatory diseases, are strongly induced in
      monocytes by direct contact with stimulated T lymphocytes. The present study
      shows that the latter mechanism is inhibited by interferon (IFN)-beta. In co
      cultures of autologous T lymphocytes and monocytes stimulated by
      phytohaemagglutinin (PHA), IFN-beta inhibited the production of TNF-alpha and IL
      1beta by 88 and 98%, respectively, whereas the simultaneous production of IL-1
      receptor antagonist (IL-1Ra), was enhanced two-fold. The latter effects of IFN
      beta were independent of modulations in IFN-gamma, IL-4 and IL-10 production.
      When monocytes were activated by plasma membranes of stimulated T cells, IFN-beta
      slightly inhibited the production of TNF-alpha and IL-1beta, while enhancing 1.5
      fold that of IL-1Ra. The latter effect correlated with the persistence of high
      steady-state levels of IL-1Ra mRNA after 24 h of activation. Membranes isolated
      from T lymphocytes that had been stimulated in the presence of IFN-beta displayed
      a 80% decrease in their capacity to induce the production of IL-1beta and TNF
      alpha in monocytes, whereas IL-1Ra induction was decreased by only 32%. These
      results demonstrate that IFN-beta modulates contact-mediated activation of
      monocytes by acting on both T lymphocytes and monocytes, decreasing the ability
      of T lymphocytes to induce TNF-alpha and IL-1beta production in monocytes and
      directly enhancing the production of IL-1Ra in the latter cells.

PMID- 11444908
TI  - Endotoxin-induced interleukin 1 expression in testicular macrophages is
      accompanied by downregulation of the constitutive expression in Sertoli cells.
AB  - Interleukin-1alpha (IL-1alpha) is constitutively produced by Sertoli cells in
      adult rat testes. We demonstrate here that adult rats initiate expression of IL
      1alpha and IL-1beta in testicular macrophages and decrease plasma testosterone by
      60%, 2 h after administration of endotoxin. The macrophage activation was
      accompanied by downregulation of IL-1alpha mRNA expression in Sertoli cells.
      Despite increased tissue concentrations of IL-1alpha and IL-1beta immunoreactive
      protein, the level of bioactive IL-1 in the testis remained unchanged. Testes
      from prepubertal rats responded similarly to endotoxin, but lacked constitutive
      expression of IL-1alpha. We conclude that endotoxin-induced inflammation involves
      the testis by local macrophage activation and cytokine secretion. The paracrine
      mechanisms regulating IL-1 bioactivity in the testis are unknown but may
      represent a means to protect germ cells from noxious effects of inflammation.

PMID- 11444909
TI  - Presence of IFN-gamma and IL-4 in human periapical granulation tissues and
      regeneration tissues.
AB  - To study mediators associated with the progression of disease and the process of
      bone regeneration in human apical periodontitis, we examined samples of
      periapical granulation tissues and regeneration tissues obtained from five
      patients by use of immunohistochemical methods. Periapical granulation tissues
      were found to contain a large number of CD4-positive T cells and CD68-positive
      monocytes/macrophages (CD4: 35.2%, CD68: 32.7%). The CD4-positive T cells and
      CD68-positive monocytes/macrophages were predominantly present in regeneration
      tissues (CD4: 62.1%, CD68: 16.0%). In these the percentages of CD4-positive T
      cells were higher as compared with periapical granulation tissues (from 35.2% to
      62.1%). In periapical granulation tissues, CD4-positive T cells stained
      positively for interferon-gamma (IFN-gamma) and negatively for interleukin-4 (IL
      4). In regeneration tissues, IL-4-producing cells could be detected. However, IFN
      gamma-producing cells could not be detected. These results suggest that IFN-gamma
      and IL-4 may modulate the pathogenesis of infectious disease and the process of
      bone regeneration in local inflammation sites such as human apical periodontitis.

PMID- 11444910
TI  - Expression of TNF-alpha mRNA by peripheral blood mononuclear cells of multiple
      sclerosis patients treated with IFN-beta 1A.
AB  - The aim of the present study was to verify the expression of tumour necrosis
      factor (TNF)-alpha mRNA by semiquantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR) in unstimulated peripheral blood mononuclear cells (MNCs)
      of 15 relapsing-remitting multiple sclerosis (MS) patients who underwent
      treatment with IFN-beta 1a (6 millions of international units (MIU) i.m. once a
      week) and in 15 untreated MS patients matched for age and expanded disability
      status score (EDSS). At the same time the expression of TNF-alpha mRNA was
      assessed in 10 healthy age-matched control subjects. All MS patients were
      assessed at the basal time and after 6 months. At the basal time, the band of TNF
      alpha mRNA was detectable in 12 out of the 15 untreated patients and in 13 out of
      the 15 patients who underwent IFN-beta 1a treatment. The higher TNF-alpha mRNA
      was evident in patients with gadolinium-enhancing lesions. At the 6-month follow
      up, 13 out of the 15 untreated patients still had detectable values of TNF-alpha
      mRNA and no significant difference emerged when compared with basal time. On the
      contrary, the expression of TNF-alpha mRNA was absent at the same time in nine
      out of the 15 patients treated with IFN-beta 1a. A longitudinal analysis carried
      out monthly in eight MS patients (four untreated and four treated) revealed a
      transient increase in TNF-alpha mRNA expression in MNCs of all four treated
      patients in the first 3 months, supporting previous findings of an early
      immunoenhancing effect of IFN-beta 1a. This early activation is followed by an
      inhibitory effect of IFN-beta 1a on TNF-alpha mRNA expression in about 2/3 of
      treated MS patients when assessed at 6 months. Further long-term studies are
      needed to confirm this immunomodulatory effect of IFN-beta 1a not only on TNF
      alpha but also on other cytokines of Th(1)and Th(2)types.

PMID- 11444911
TI  - Differences in the expression of CD64 and mCD14 on polymorphonuclear cells and on
      monocytes in patients with septic shock.
AB  - The present study was performed to clarify the time course of the expression of
      CD64, the Fc gamma receptor type I (FcgammaR1), and membrane-bound CD14 (mCD14),
      one of the major receptors for endotoxin, on polymorphonuclear leukocytes (PMN)
      and monocytes in 22 postoperative/post-traumatic patients with septic shock.
      Therefore, the expression of CD64 and mCD14, and serum concentrations of
      granulocyte colony-stimulating factor (G-CSF) and interferon-gamma (IFN-gamma)
      were determined by flow cytometric analysis and enzyme-linked immunosorbent assay
      (ELISA), respectively, from the first day of septic shock onwards over a period
      of 14 days. When compared to the values of 12 healthy controls, CD64 expression
      was elevated significantly on PMN and monocytes of the patients, whereas the
      expression of mCD14 was decreased significantly at all days. The initially
      increased expression of CD64 on PMN and monocytes decreased within the first days
      of septic shock. The already initially decreased mCD14 expression decreased
      further on PMN, but not on monocytes. Serum concentrations of G-CSF and IFN-gamma
      during the study period were significantly higher than those of the control
      group. The differences in the kinetics of CD64 and mCD14 expression in patients
      with septic shock may be explained by different regulatory effects of cytokines,
      such as G-CSF and IFN-gamma.

PMID- 11444912
TI  - Signaling pathways mediated by the beta(2)-adrenergic receptor in the fibroblast:
      a novel role for PI 3-kinase.

PMID- 11444913
TI  - SERCA pump level is a critical determinant of Ca(2+)homeostasis and cardiac
      contractility.
AB  - The control of intracellular calcium is central to regulation of cardiac
      contractility. A defect in SR Ca(2+)transport and SR Ca(2+)ATPase pump activity
      and expression level has been implicated as a major player in cardiac
      dysfunction. However, a precise cause-effect relationship between alterations in
      SERCA pump level and cardiac contractility could not be established from these
      studies. Progress in transgenic mouse technology and adenoviral gene transfer has
      provided new tools to investigate the role of SERCA pump level in the heart. This
      review focuses on how alterations in SERCA level affect Ca(2+)homeostasis and
      cardiac contractility. It discusses the consequences of altered SERCA pump levels
      for the expression and activity of other Ca(2+)handling proteins. Furthermore,
      the use of SERCA pump as a therapeutic target for gene therapy of heart failure
      is evaluated.

PMID- 11444914
TI  - Mitochondrial dysfunction in cardiac disease: ischemia--reperfusion, aging, and
      heart failure.
AB  - Mitochondria contribute to cardiac dysfunction and myocyte injury via a loss of
      metabolic capacity and by the production and release of toxic products. This
      article discusses aspects of mitochondrial structure and metabolism that are
      pertinent to the role of mitochondria in cardiac disease. Generalized mechanisms
      of mitochondrial-derived myocyte injury are also discussed, as are the strengths
      and weaknesses of experimental models used to study the contribution of
      mitochondria to cardiac injury. Finally, the involvement of mitochondria in the
      pathogenesis of specific cardiac disease states (ischemia, reperfusion, aging,
      ischemic preconditioning, and cardiomyopathy) is addressed.

PMID- 11444915
TI  - beta-Adrenergic stimulation of rat cardiac fibroblasts promotes protein synthesis
      via the activation of phosphatidylinositol 3-kinase.
AB  - beta -adrenergic agonists stimulate neonatal rat cardiac fibroblast growth,
      albeit the identity of the signaling event(s) remains equivocal. Isoproterenol
      (ISO) treatment increased intracellular cyclic AMP levels; however, cyclic AMP
      elevating agents had no effect on protein synthesis. The tyrosine kinase
      inhibitor tyrphostin A25, and the inhibition of ras processing by the
      farnesyltransferase inhibitor BMS-191563 attenuated ISO-stimulated protein
      synthesis. Concomitant with increased protein synthesis, ISO stimulated
      extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3
      kinase (PI3-K) activity. The MEK1/2 inhibitor PD098059 abrogated ISO-stimulated
      ERK activity, albeit the increase in protein synthesis was unaffected. By
      contrast, LY294002 inhibited both ISO-stimulated PI3-K activity, and protein
      synthesis. ISO treatment did not increase the expression of transforming growth
      factor-beta(1)(TGF-beta(1)) mRNA, whereas a significant decrease in the steady
      state mRNA level of TGF- beta(3)was observed. This latter effect was mimicked by
      cyclic AMP-elevating agents. Angiotensin II (AII) activation of the AT(1)receptor
      increased protein synthesis, but in contrast to ISO, the growth response was not
      inhibited by either tyrphostin A25 or BMS-191563, and was associated with the
      concomitant expression of both TGF-beta(1)and TGF-beta(3)mRNAs. Analogous to ISO,
      AII treatment increased ERK and PI3-K activity, and PI3-K was required for
      protein synthesis. These findings are the first to highlight the activation of
      PI3-K by a Gs(alpha)-coupled receptor, and its essential role in beta -adrenergic
      as well as AT(1)receptor-mediated protein synthesis in neonatal rat cardiac
      fibroblasts. However, despite the conserved role of PI3-K, additional disparate
      signaling pathways are recruited by ISO and AII, which may differentially
      influence fibroblast phenotype.

PMID- 11444916
TI  - Prostaglandins and nitric oxide mediate superoxide-induced myocardial contractile
      dysfunction in isolated rat hearts.
AB  - Oxygen-derived free radicals have been implicated in the pathogenesis of
      myocardial injury. We therefore investigated the pathophysiology of myocardial
      injury induced in isolated rat hearts by perfusion with superoxide radical
      generated by reacting 2.5 mmol/l purine, 0.03 U/ml xanthine oxidase and 300 U/ml
      catalase. Perfusion with superoxide significantly (P<0.05) increased left
      ventricular end-diastolic pressure within 15 to 20 min. During the same time
      period, heart rate and left-ventricular developed pressure significantly declined
      to 44.6+/-8.2% and 31.0+/-4.9% of control, respectively. Superoxide perfusion
      also significantly increased production of prostaglandins, nitric oxide (detected
      as nitrites) and peroxynitrite (detected immunohistochemically as nitrotyrosine).
      N(G)-nitro-l-arginine (100 micromol/l), a nitric oxide synthase inhibitor,
      attenuated superoxide-induced generation of peroxynitrite, increased synthesis of
      prostacyclin, and partially blocked myocardial dysfunction, as did 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (30 micromol/l), a selective inhibitor
      of soluble guanylate cyclase, and ONO-3708 (10 micromol/l), a selective
      thromboxane A(2)receptor antagonist. In contrast, nitroglycerin (4 micromol/l)
      and sodium nitroprusside (1 micromol/l) each exacerbated the superoxide-induced
      myocardial dysfunction. These results suggest that nitric oxide and related
      reactive species contribute to myocardial injury induced by superoxide. Moreover,
      they suggest that oxidative stress can be delayed or inhibited by reducing levels
      of nitric oxide, by inhibiting soluble guanylate cyclase, and by blocking
      thromboxane/prostaglandin receptors.

PMID- 11444917
TI  - Phenotypic properties and characteristics of superoxide production by mouse
      coronary microvascular endothelial cells.
AB  - Coronary microvascular endothelial cells exert (patho)physiological effects on
      the function of cardiac myocytes, which may be studied experimentally using pure
      cell populations. As an essential pre-requisite to the investigation of cells
      from gene-modified mice, we studied the phenotypic properties of coronary
      microvascular endothelial cells isolated from normal mice, and biochemically
      characterized the superoxide production by these cells. Microvascular endothelial
      cells were isolated from devitalized mouse ventricular tissue after sequential
      digestion with collagenase, trypsin and DNase. Coronary microvascular endothelial
      cells were separated from cardiac myocytes and other cells by differential
      centrifugation, plating and culture. Mouse coronary microvascular endothelial
      cells showed an irregular "cobblestone" morphology at confluence, were >98%
      positive for CD31 by FACS analysis, and were also positive for VE-cadherin and
      endothelial-type nitric oxide synthase (eNOS) by confocal microscopy. The cells
      took up fluorescently labelled, acetylated low-density lipoprotein, but were
      negative for a alpha -smooth muscle actin, desmin and cytokeratin. Unlike human
      endothelial cells, mouse coronary microvascular endothelial cells only weakly
      expressed von Willebrand factor. Immunoblotting showed that the mouse cells
      expressed components of a phagocyte-type NADPH oxidase. They exhibited NADPH
      dependent O(2)(-)-generating activity, which was increased by angiotensin II but
      completely inhibited by diphenyleneiodonium. Thus, mouse coronary microvascular
      endothelial cells express both eNOS and NADPH oxidase, interactions between which
      may play a role in endothelial cell pathophysiology.

PMID- 11444918
TI  - Intracellular calcium level required for calpain activation in a single
      myocardial cell.
AB  - We have hypothesized that calpain mediates myocardial injury induced by
      Ca(2+)overload. However, in vitro study demonstrated that the calcium requirement
      for calpain activation is around 10 microm, which is difficult to reach without
      the cell collapsing. Furthermore, because calpastatin is abundant in the
      myocardial cell, calpain may not be activated in physiological conditions. To
      elucidate whether calpain is activated by the calcium concentration reachable in
      myocardial living cells, we measured the calpain activity and the calcium
      concentration simultaneously in isolated guinea-pig cardiomyocytes. t
      Butoxycarbonyl-Leu-Met-7-amino-4chlorimethylcoumarin (Boc-Leu-Met-CMAC), a
      fluorescent substrate of calpain, and/or fura red, a calcium indicator, were
      loaded into isolated cardiomyocytes together, and their fluorescence were
      measured separately. Intracellular Ca overload was induced by changing the
      superfusate from normal Tyrode solution to a sodium-free one. After changing the
      solution, fluorescence intensity of fura red and Boc-Leu-Met-CMAC did not change
      for a while, then fluorescence intensity of fura red began to rise. This was
      followed by the fluorescence intensity of Boc-Leu-Met-CMAC starting to rise 160+/
      45 s after [Ca(2+)](i)increase. The relative fluorescence intensity of fura red
      increased to 1.37+/-0.32 folds of the control at the point that calpain became
      active. The calcium concentration at this point was estimated as 451 n m. These
      results indicate that calpain is activated by the slight rise of Ca concentration
      in intact cardiomyocytes.

PMID- 11444919
TI  - Characterization of an NBTI-sensitive equilibrative nucleoside transporter in
      vascular smooth muscle.
AB  - Adenosine plays a significant role in various physiological and regulatory
      processes including coronary vasodilatation. In the current study, a high
      affinity adenosine transporter in freshly dissociated porcine coronary smooth
      muscle (PCSM) cells and cultured human coronary smooth muscle (HCSM) cells was
      characterized. Kinetic analysis of the transport process revealed a V(max) of
      82+/-17 pm/mg protein/min and a K(m) of 4.3+/-2.1 microm for PCSM cells, whereas
      a K(m) of 4.8 microm and V(max) of 254 pm/mg/min was observed for cultured HCSM.
      Concentration-dependent inhibition of adenosine uptake by S-(4-nitrobenzyl)-6
      thioinosine (NBTI) was observed in both PCSM (IC(50), 0.08 microm) and HCSM (0.1
      microm) cells. Both cell types also demonstrate a high-affinity, single binding
      site for NBTI (PCSM, B(max) 144.8+/-23 fmol/mg protein and K(d) 1.1+/-0.35 nm;
      HCSM, B(max) 672+/-62 fmol/mg protein and K(d) 0.45+/-0.14 nm). Adenosine uptake
      in these cells was not affected by extracellular sodium concentration. RT-PCR
      analysis of mRNA from individually selected PCSM and HCSM cells demonstrated
      expression of an NBTI-sensitive equilibrative transporter. Smooth muscle cells
      isolated from porcine brachial and femoral arteries also transported adenosine at
      levels similar to that of coronaries. These data demonstrate that vascular
      coronary smooth muscle possess an NBTI-sensitive equilibrative transporter for
      adenosine which could function in regulation of vasodilation.

PMID- 11444920
TI  - Autoantibodies from mothers of children with congenital heart block downregulate
      cardiac L-type Ca channels.
AB  - Congenital heart block (CHB) affects offspring of mothers with autoantibodies
      (positive IgG) to intracellular SSA/Ro and SSB/La ribonucleoproteins and is
      associated with high morbidity and mortality. Here, we show that maternal anti
      Ro/La antibodies immunoreact with human fetal cardiomyocyte sarcolemma, recognize
      human L-type Ca channel alpha(1C)-protein and functionally inhibit expressed
      current in oocytes injected with alpha(1C) cRNA and Purkinje L-type Ca current.
      Furthermore, cardiac myocytes from pups born to SSA/Ro-immunized mice exhibited
      reduced L-type Ca current density. All together, the data establish that L-type
      calcium channel is a target for maternal antibodies and may provide a functional
      basis for the electrocardiographic abnormalities seen in infants with CHB.

PMID- 11444921
TI  - Ischemic loss of sarcolemmal dystrophin and spectrin: correlation with myocardial
      injury.
AB  - Sarcolemmal blebbing and rupture are prominent features of irreversible ischemic
      myocardial injury. Dystrophin and spectrin are sarcolemmal structural proteins.
      Dystrophin links the transmembrane dystroglycan complex and extracellular laminin
      receptors to intracellular F-actin. Spectrin forms the backbone of the membrane
      skeleton conferring an elastic modulus to the sarcolemmal membrane. An ischemic
      loss of membrane dystrophin and spectrin, in ischemically pelleted rabbit
      cardiomyocytes or in vivo 30--45 min permanently ischemic, LAD-ligated hearts,
      was detected by immunofluorescence with monoclonal antibodies. Western blots of
      light and heavy microsomal vesicles and Triton-extracted membrane fractions from
      ischemic myocytes demonstrated a rapid loss of dystrophin coincident with sub
      sarcolemmal bleb formation, subsequent to a hypotonic challenge. The loss of
      spectrin from purified sarcolemma of autolysed rabbit heart, and both isolated
      membrane vesicles and Triton solubilized membrane fractions of ischemic
      cardiomyocytes correlated linearly with the onset of osmotic fragility as
      assessed by membrane rupture, subsequent to a hypotonic challenge. In contrast to
      the ischemic loss of dystrophin and spectrin from the membrane, the dystrophin
      associated proteins, alpha-sarcoglycan and beta-dystroglycan and the integral
      membrane protein, sodium-calcium exchanger, were maintained in the membrane
      fraction of ischemic cells as compared to oxygenated cells. Preconditioning
      protected cells, but did not significantly alter ischemic dystrophin or spectrin
      translocation. This previously unrecognized loss of sarcolemmal dystrophin and
      spectrin may be the molecular basis for sub-sarcolemmal bleb formation and
      membrane fragility during the transition from reversible to irreversible ischemic
      myocardial injury.

PMID- 11444922
TI  - TGF-beta(1) downregulates PTHrP in coronary endothelial cells.
AB  - Parathyroid hormone-related peptide (PTHrP) is expressed throughout the
      cardiovascular system including coronary endothelial cells. Factors involved in
      the regulation of cardiac PTHrP expression have not been examined before. This
      study investigates the influence of transforming growth factor (TGF)-beta(1)on
      ventricular PTHrP expression. Coronary endothelial cells were isolated from
      ventricles of adult rats and PTHrP protein expression in these cultures was
      analysed by immunoblotting. TGF-beta(1)caused a concentration-dependent reduction
      in PTHrP protein within 24 h. In transgenic mice over-expressing TGF
      beta(1)ventricular PTHrP protein expression and release was reduced compared to
      non-transgenic littermates. Similar concerns hold for PTHrP mRNA content (RT
      PCR). Since ventricular TGF-beta(1)expression increases under pathophysiological
      conditions like arterial hypertension, ventricular PTHrP expression was further
      determined in aging spontaneously hypertensive (SHR-SP) and normotensive rats.
      TGF- beta(1)expression was increased in SHR-SP and ventricular PTHrP mRNA
      expression was downregulated at the age of 10 months. PTHrP expression did not
      recover in elder SHR-SP in which TGF-beta(1)expression was normalized again.
      Finally, we investigated ventricular PTHrP expression in rats after banding of
      the ascending aorta which generates a pressure induced hypertrophy without an
      induction of TGF-beta(1)expression. In ventricles from these animals, PTHrP
      expression was transiently increased and normalized at day 3. In conclusion,
      PTHrP expression was reduced under all conditions in which coronary endothelial
      cells were exposed to TGF-beta(1). PTHrP expression does not correlate with
      cardiac hypertrophy. Since coronary endothelial cells represent the majority of
      PTHrP producing cells in the ventricle its downregulation by TGF- beta(1)seems to
      be relevant for the paracrine effects of PTHrP.

PMID- 11444923
TI  - Changes in extracellular matrix and in transforming growth factor beta isoforms
      after coronary artery ligation in rats.
AB  - Extensive myocardial remodeling occurs after transmural myocardial infarction
      (MI). The infarcted myocardium is being replaced by scar tissue after gradual
      resorption of the necrotic tissue. The remodeling process involves both synthesis
      and degradation of collagens as major components of the extracellular matrix
      (ECM). In the present study we have analyzed the time-dependent changes of the
      processes related to this fibrosis in the infarct area and in the non-infarcted
      left ventricle (LV) six hours to 82 days after occlusion of the left anterior
      descending coronary artery (LAD) in rats. We also examined whether changes
      occurred in the expression pattern of the transforming growth factor (TGF) beta
      isoforms, since this cytokine is known as powerful inductor of fibrosis.
      Elevation in colligin expression preceded the pronounced increase in mRNA
      expression of both type I and type III collagen after MI from day three onwards.
      The maximal increase in colligin protein in the infarct area coincided with the
      most pronounced expression of collagen I and collagen III mRNA expression. Also,
      the expression and activity of matrix metalloproteinases (MMPs) and of tissue
      inhibitor of matrix metalloproteinase (TIMP)-2 mRNA were increased predominantly
      in the infarct area. TGF beta(1)and TGF-beta(2)expression increased within the
      first days after MI, whereas TGF-beta(3)expression was elevated predominantly in
      the infarct area. This pronounced increase in TGF-beta(3)persisted up to 82 days
      and correlated positively with the parameters of ECM metabolism. Thus, the scar
      formation is an ongoing dynamic process in which TGF-beta(3)seems to play an
      active role in the complex ventricular remodeling.

PMID- 11444924
TI  - Heat shock protein-56 is induced by cardiotrophin-1 and mediates its hypertrophic
      effect.
AB  - Cardiotrophin-1 (CT-1) is an interleukin-6 family cytokine with known protective
      and hypertrophic effects in the heart. Previous studies have shown that CT-1
      treatment increases heat shock protein 70 (hsp70) and heat shock protein 90
      (hsp90) levels in cardiac cells. Due to the known protective effects of hsp90 and
      hsp70, induction of these proteins may be involved in the protective effects of
      CT-1. We show here that heat shock protein 56 (hsp56), also known as FK506
      binding protein 59 (FKBP59), is induced by CT-1 treatment at both the mRNA and
      protein levels. It has been demonstrated previously that, unlike hsp70 and hsp90,
      hsp56 overexpression does not protect cardiac myocytes against stressful stimuli.
      The other known effect of CT-1 is hypertrophy, an increase in cell size without
      cell division, which occurs in many cardiac pathologies. We investigated the role
      of hsp56 in the hypertrophic response of primary neonatal rat cardiac myocytes,
      using overexpression with transiently transfected plasmid vectors and Herpes
      viral vectors. Overexpression of hsp56 caused a significant increase in cardiac
      cell size and protein:DNA ratio. Hsp27, hsp70 and hsp90 overexpression had no
      effect on cell size. An antisense construct to hsp56 reduced hsp56 levels when
      transiently transfected and blocked the hypertrophic effect of CT-1. This is the
      first time that a hypertrophic effect has been demonstrated for a heat shock
      protein and demonstrates that CT-1-induced hypertrophy involves a specific hsp,
      which is not involved in its protective effect.

PMID- 11444925
TI  - Effect of NF-kappa B Inhibition on TNF-alpha-induced apoptosis and downstream
      pathways in cardiomyocytes.
AB  - Heart-specific inhibition of survival pathway gp130 was recently shown to
      sensitize transgenic mice towards stress stimuli, resulting in rapid onset of
      cardiac dilatation and heart failure. In order to identify further survival
      pathways we evaluated the role of transcription factor nuclear factor-kappa B (NF
      kappa B) in tumour necrosis factor-alpha (TNF-alpha)-induced apoptosis of
      cardiomyocytes. TNF-alpha stimulation (10 ng/ml) of both H9c2 cells and primary
      cardiomyocytes isolated from neonatal Wistar rats resulted in rapid nuclear
      translocation of NF-kappa B complexes. The NF-kappa B complexes consisted of rel
      proteins p50 and p65, as revealed by supershift analysis. Addition of proteasome
      inhibitor MG132 or adenoviral expression of a truncated I kappa B alpha (I kappa
      B Delta N) inhibited TNF-alpha-induced NF-kappa B nuclear translocation in a dose
      dependent manner. Both neonatal cardiomyocytes and H9c2 cells were resistant to
      TNF-induced apoptosis. However, specific inhibition of NF-kappa B activation by
      Ad5-I kappa B alpha Delta N (MOI=50) or MG132 (5 microm) increased apoptosis as
      measured by subG1-assay (H9c2 cells) and annexin V binding/propidium iodide
      (neonatal cardiomyocytes, FACS-analysis: 7+/-2% to 26+/-5% annexin V positive/PI
      negative), respectively. TUNEL-assay double-stained with anti-alpha-sarcomeric
      actin confirmed apoptosis of neonatal cardiomyocytes. Furthermore, caspase-3
      activation was increased by 52+/-7% in neonatal cardiomyocytes after TNF
      alpha+Ad5-I kappa B alpha Delta N compared to TNF alpha+Ad5-control treatment.
      Protein levels of hiAP1, hiAP2, x-iAP, bcl-2 and bcl-x(L) were neither
      downregulated by NF-kappa B inhibition nor upregulated by TNF-alpha stimulation.
      In summary, cardiomyocytes utilize transcription factor NF-kappa B to activate
      survival factors in the context of TNF-alpha stimulation. As locally increased
      levels of TNF-alpha have been detected in heart failure, NF-kappa B activity is
      essential for cellular homeostasis in the heart.

PMID- 11444926
TI  - Modulation of outward potassium currents in aligned cultures of neonatal rat
      ventricular myocytes during phorbol ester-induced hypertrophy.
AB  - Protein kinase C-stimulating phorbol esters induce a strong hypertrophic response
      when applied in vitro to cardiac ventricular myocytes. The aim of this study was
      to determine if this in vitro model of hypertrophy is associated with changes in
      the expression of voltage-gated K(+)channels. Myocytes were isolated from 3--4
      day-old neonatal rats and cultured on aligned collagen thin gels. Membrane
      currents were measured with the use of the whole-cell arrangement of the patch
      clamp technique and the expression levels of the Kv1.4, Kv4.2 and Kv2.1 alpha
      subunits quantified using Western blot analysis. Voltage steps positive to -30 mV
      resulted in the activation of both a transient (I(to)) and a sustained (I(sus))
      component of outward K(+)current in the aligned myocytes. Overnight exposure to
      phorbol 12-myristate 13-acetate (PMA) caused a 55% increase in myocyte size and a
      three-fold reduction in the peak amplitude of I(to). No differences in the half
      maximal voltages required for activation and steady-state inactivation were
      observed between I(to)measured in control and PMA-treated myocytes. In contrast,
      PMA treatment resulted in a 62% increase in a tetraethylammonium-sensitive
      component of I(sus)(TEA-I(sus)) and was associated with the appearance of a slow
      component of current decay. Expression levels of the Kv1.4 and Kv4.2 alpha
      subunits were strongly depressed in the hypertrophic myocytes, while the density
      of the Kv2.1 alpha subunit was enhanced. PMA-induced changes in the Kv alpha
      subunits were partially prevented through inhibition of the mitogen-activated
      protein kinase (MAPK) pathway. Thus, PMA-induced hypertrophy of cultured
      ventricular myocytes is associated with an altered expression of voltage-gated
      K(+)channels.

PMID- 11444927
TI  - Activation of A(3)adenosine receptor protects against doxorubicin-induced
      cardiotoxicity.
AB  - Adenosine exerts a marked protective effect on the heart during cardiac ischemia.
      This protection is mediated by binding to the A(1)and A(3)subtypes of adenosine
      receptor (A(1)R and A(3)R, respectively). The objective of the present study was
      to investigate whether activation of A(1)and A(3)adenosine receptors may reduce
      doxorubicin-induced damage to cardiomyocytes in culture. Cultured cardiomyocytes
      from newborn rats were treated with 0.5--5 microm doxorubicin (DOX) for 18 h and
      then incubated in drug-free medium for an additional 24 h. This treatment
      resulted in cell damage and lactate dehydrogenase release, even after low (0.5
      microm) doses of the drug, and increased in a concentration-dependent manner.
      Activation of A(3)-subtype but not A(1)-subtype receptors attenuated doxorubicin
      cardiotoxicity after drug treatment for 18 h followed by 24 h incubation in drug
      free medium. Modulation of intracellular calcium mediated by activation of A(3)R,
      but not by A(1)R, in cultured myocytes suggested an important pathophysiological
      significance of this subtype of adenosine receptors. Protection by A(3)R agonist
      Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) following
      DOX treatment is evident in: (1) decreases in intracellular calcium overloading
      and abnormalities in Ca(2+)transients; (2) reduction of free-radical generation
      and lipid peroxidation; (3) attenuation of mitochondrial damage by protection of
      the terminal link (COX-complex) of respiratory chain; (4) attenuation of the
      decrease in ATP production and irreversible cardiomyocyte damage.
      Cardioprotection caused by Cl-IB-MECA was antagonized considerably by the
      selective A(3)adenosine receptor antagonist MRS1523.

PMID- 11444928
TI  - Differential regulation of myocardial NF kappa B following acute or chronic TNF
      alpha exposure.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a critical mediator of myocardial
      dysfunction during acute inflammatory states. TNF-alpha is also present in the
      serum of patients with chronic cardiac diseases. In monocytes, TNF-alpha
      stimulates cells by activating distinct signaling pathways that involve nuclear
      translocation of NF kappa B. Since NF kappa B may also regulate the expression of
      genes that could contribute to myocardial dysfunction, the cardiomyocyte NF kappa
      B activation following acute or chronic TNF-alpha challenges was investigated. To
      accomplish this, the authors either acutely administered TNF-alpha to healthy
      mice, or used transgenic mice which chronically overexpress TNF-alpha exclusively
      in cardiac myocytes. Following acute administration of TNF-alpha, cardiac NF
      kappa B translocation was detected from 15 min to 2 h post-challenge. The time
      course of I kappa B alpha degradation was consistent with the kinetics of NF
      kappa B translocation. I kappa B beta degradation was slower and less dramatic.
      In transgenic mice chronically overexpressing TNF-alpha, myocardial NF kappa B
      activation was detected at all ages tested (21, 40, and 75 days). In contrast to
      acutely challenged animals, two distinct NF kappa B proteins were activated in
      chronically challenged animals, p50--65 heterodimers as well as p50 homodimers.
      Activation of both could be transiently blocked by administration of a
      recombinant chimeric TNF-alpha receptor antagonist (rhTNFR:Fc). I kappa B alpha,
      but not I kappa B beta, levels were elevated in transgenics when compared to wild
      type animals. These data indicate that following acute TNF-alpha administration,
      which simulates bacterial sepsis, myocardial p50-p65 translocates within minutes.
      Chronic TNF-alpha exposure, which is thought to occur in long-standing congestive
      heart failure, results in translocation of transcriptionally inactive p50
      homodimers in addition to transcriptionally active p50--65 heterodimers. It is
      speculated that activation of p50 homodimers constitutes an adaptive response to
      minimize the inflammatory consequences of chronic cardiac TNF-alpha exposure.

PMID- 11444929
TI  - Expression and activity of ectopeptidases in fibrillating human atria.
AB  - Recent studies have demonstrated that atrial fibrillation (AF) occurs in the
      presence of degenerative changes of atrial tissue. In contrast, bradykinin (BK)
      appears to have cardioprotective effects diminishing myocardial hypertrophy and
      fibrosis. It is unknown, however, whether AF has direct effects on BK metabolism.
      Therefore, the purpose of this study was to determine the atrial expression of
      the membrane-bound peptidases, also referred to as ectopeptidases,
      carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPIV), and alanyl
      aminopeptidase (APN) in patients with and without AF. Atrial tissue samples of 35
      patients undergoing open heart surgery were examined. Seventeen patients had
      chronic persistent AF (> or = 6 months; CAF), the remaining 18 patients
      (controls) had no history of AF. Peptidase expression was analyzed at the mRNA
      (quantitative RT-PCR) level and apparent changes were confirmed at the protein
      level. In case of unaltered mRNA levels, enzyme activity was determined. Reduced
      amounts of CPM-mRNA were found in patients with CAF (41.3+/-9.7 U nu controls:
      86.1+/-17.5 U P<0.05). CPM protein was decreased to 47.5% in patients with CAF
      compared with controls (P<0.01). DPIV and APN mRNA amounts were similar in both
      groups. DPIV activity, however, was increased during CAF (219.6+/-30 pkat/mg
      protein v controls: 195.8+/-21.8 pkat/mg P<0.05). APN activity was unchanged. In
      conclusion, atrial bradykinin metabolizing activities are significantly altered
      during AF in humans. The observed alterations in ectopeptidase
      expression/activity may play a role in the structural remodeling of fibrillating
      atria.

PMID- 11444930
TI  - Beta-adrenergic receptors and calcium cycling proteins in non-failing,
      hypertrophied and failing human hearts: transition from hypertrophy to failure.
AB  - Left ventricular hypertrophy may lead to heart failure. The transition between
      hypertrophy and heart failure is, however, incompletely understood. On the
      cellular level, human heart failure is characterized by alterations in Ca(2+)
      cycling proteins and beta-adrenergic receptor density, but the hypertrophied
      human heart remains largely under studied. In this investigation, 21 donor hearts
      which could not be used for transplantation were studied. Ten of these hearts
      came from organ donors with documented left ventricular hypertrophy and normal
      cardiac function. Eleven of the hearts were non-failing, obtained from
      individuals with no evidence of cardiac disease. Nine failing hearts from
      transplant recipients were also studied. beta-adrenergic receptor density was
      determined by radioligand binding. mRNA for atrial natriuretic factor,
      calsequestrin, sarcoplasmic reticulum Ca(2+)-ATPase, and phospholamban was
      measured by Northern blot. Actin, calsequestrin, sarcoplasmic reticulum Ca(2+)
      ATPase, and phospholamban proteins were quantified by Western blot. In both
      hypertrophied and failing ventricles, mRNA for atrial natriuretic factor was
      expressed, as compared to no expression in non-failing hearts. In failing hearts,
      beta -adrenergic receptor density and both mRNA and protein levels of the Ca(2+)
      ATPase were significantly decreased v non-failing hearts. By comparison,
      hypertrophied hearts showed a reduction in mRNA expression for both the Ca(2+)
      ATPase and phospholamban with no change in the corresponding protein levels, and
      no change in beta-receptors. These data suggest that the previously demonstrated
      reduction in beta-adrenergic receptors and Ca(2+)-cycling proteins in the failing
      human heart may be features of the decompensated state, but are not found in
      human hearts with left ventricular hypertrophy and preserved systolic function.

PMID- 11444931
TI  - Calculation of 13C chemical shifts in rna nucleosides: structure-13C chemical
      shift relationships.
AB  - Isotropic 13C chemical shifts of the ribose sugar in model RNA nucleosides are
      calculated using SCF and DFT-GIAO ab initio methods for different combinations of
      ribose sugar pucker, exocyclic torsion angle, and glycosidic torsion angle.
      Idealized conformations were obtained using structures that were fully optimized
      by ab initio DFT methods starting with averaged parameters from a collection of
      crystallographic data. Solid-state coordinates of accurate crystal or neutron
      diffraction structures were also examined directly without optimization. The
      resulting 13C chemical shifts for the two sets of calculations are then compared.
      The GIAO-DFT method overestimates the shifts by an average of 5 ppm while the
      GIAO-SCF underestimates the shifts by the same amount. However, in the majority
      of cases the errors appear to be systematic, as the slope of a plot of calculated
      vs experimental shifts is very close to unity, with minimal scatter. The values
      of the 13C NMR shifts of the ribose sugar are therefore sufficiently precise to
      allow for statistical separation of sugar puckering modes and exocyclic torsion
      angle conformers, based on the canonical equation model formulated in a previous
      paper.

PMID- 11444932
TI  - Modeling magnetization transfer using a three-pool model and physically
      meaningful constraints on the fitting parameters.
AB  - A model for water-macromolecular magnetization transfer is presented which
      addresses the mechanism of coupling between the hydrogen populations and the
      extraction of physically meaningful parameters from experimental magnetization
      transfer data. Both physical exchange between bulk-solvent and site-specific
      hydration-layer hydrogens and intermolecular magnetic dipolar coupling between
      these specific hydration-layer-solvent and macromolecular hydrogens are
      explicitly included, leading to a three-pool model for magnetization transfer. It
      is shown that the three-pool model is well approximated by a two-pool model for
      coupling between the bulk-solvent and macromolecular hydrogens when the dipolar
      coupled solvent hydrogens are a small fraction of the total solvent, and the
      solvent-macromolecular coupling constant includes both dipolar magnetic,
      kappa(dip), and physical exchange, kappa(ex), coupling rates. The model is also
      extended to multiple solvent systems. The model results in a set of coupled
      equations that predict magnetization transfer spectra as a function of
      temperature and composition. Physically meaningful constraints on the coupling
      and relaxation parameters are established for systems in which magnetization
      transfer has been observed including solvated cross-linked proteins and lipid
      bilayers. Using parameter estimates based on these constraints, empirical
      magnetization transfer spectra are well predicted by the model. It is found that
      the degree of magnetization transfer becomes independent of kappa(dip) and
      kappa(ex) when these parameters become greater than about 50 s(-1). In the semi
      rigid cross-linked protein systems where the mobility of the macromolecular
      matrix is insensitive to temperature, the magnitude of the observed magnetization
      transfer is consistent with being limited by the intermolecular dipolar coupling
      and spin-lattice relaxation in the bulk-solvent phase.

PMID- 11444933
TI  - Difftrain: a novel approach to a true spectroscopic single-scan diffusion
      measurement.
AB  - Diffusion-ordered spectroscopy (DOSY) has gained considerable attention over the
      past decade as a useful tool for calculating diffusion-related parameters or in
      the analysis of complex (reaction) mixtures. A major drawback of the established
      methods are the relatively long recording times needed to acquire the spectra,
      excluding the monitoring of rapidly progressing reactions and (hence)
      measurements of less stable components. In order to overcome these shortcomings a
      new pulse sequence, Difftrain, has been developed. The sequence involves
      stimulated echo attenuation, multilow flip angle excitation, and multiple
      sampling of the FID during the longitudinal storage. The calculated diffusion
      parameters obtained by Difftrain were compared with those obtained by the
      established sequence BPPSTE (bipolar pulse pair stimulated echo) and were in good
      agreement. For systems with moderate to good signal-to-noise ratios the Difftrain
      building block yields significant saving in recording time (single-shot
      acquisition instead of acquiring n-different gradients strengths), thus opening
      up new applications in nonequilibrium systems and screening of compositions
      and/or interactions of (larger) compound arrays.

PMID- 11444934
TI  - Analytical solution to the Lipari-Szabo model based on the reduced spectral
      density approximation offers a novel protocol for extracting motional parameters.
AB  - An analytical solution to the Lipari-Szabo model is derived for isotropic overall
      tumbling. The parameters of the original Lipari-Szabo model, the order parameter
      S2 and the effective internal correlation time tau(e), are calculated from two
      values of the spectral density function. If additionally the spectral density
      value J(0) is known, the exchange contribution R(ex) term can also be determined.
      The overall tumbling time tau(c) must be determined in advance, for example, from
      T1/T2 ratios. The required spectral density values are obtained by reduced
      spectral density mapping from T1, T2, and NOE measurements. Our computer
      simulations show that the reduced spectral density mapping is a very good
      approximation in almost all cases in which the Lipari-Szabo model is applicable.
      The robustness of the analytical formula to experimental errors is also
      investigated by extensive computer simulations and is found to be similar to that
      of the fitting procedures. The derived formulas were applied to the experimental
      15N relaxation data of ubiquitin. Our results agree well with the published
      parameter values of S2 and tau(e), which were obtained from standard fitting
      procedures. The analytical approach to extract parameters of molecular motions
      may be more robust than standard analyses and provides a safeguard against
      spurious fitting results, especially for determining the exchange contribution
      R(ex).

PMID- 11444935
TI  - Spectral editing in solid-state NMR using scalar multiple quantum filters.
AB  - In this paper we describe the use of heteronuclear scalar couplings in solid
      state NMR in order to generate multiple-quantum filtering (MQF) pulse sequences.
      These sequences can be used to edit CP/MAS spectra according to carbon
      multiplicity. Analytic expressions for the intensity of the MQF signals are
      obtained using the standard product operator formalism. Experiments that
      demonstrate the technique are shown in powder samples of camphor and a
      tripeptide.

PMID- 11444936
TI  - A general strategy for the NMR observation of half-integer quadrupolar nuclei in
      dilute environments.
AB  - A general strategy for the observation of low gamma half-integer quadrupolar
      nuclides in biological systems is presented. The methodology combines low
      temperature (4-100 K) techniques with cross-polarization (CP) experiments while
      employing a so-called Carr-Purcell-Meiboom-Gill spin-echo sequence (CPMG). This
      combined approach is termed CP/QCPMG. Also discussed are data processing issues
      that are unique to the induced signals that result from the QCPMG pulse sequence.
      Central to this strategy is the development of a stable low-temperature (4 to 250
      K) NMR double-resonance probe. The probe is robust enough to handle multiple
      contact experiments and long acquisition periods with 1H decoupling. This
      approach is illustrated with low-temperature solid-state 67Zn and 25Mg NMR
      CP/QCPMG experiments on model compounds. The conclusion reached is that the
      strategy affords sufficient sensitivity to examine Zn2+ and/or Mg2+ binding sites
      in metalloproteins.

PMID- 11444937
TI  - J-modulated TROSY experiment extends the limits of homonuclear coupling
      measurements for larger proteins.
AB  - This paper describes the use of a TROSY experimental scheme and its variant
      extended with a scaled J-modulation spin-echo sequence for accurate and sensitive
      measurement of homonuclear 3J(H(N)H(alpha)) coupling constants in larger proteins
      with uniform 15N labeling. Exclusive selection of the most slowly relaxing
      component of a 15N-1H multiplet by the TROSY approach leads to substantial
      improvement in resolution; this is a prerequisite for accurate measurement of
      couplings from the 1H multiplets directly along the 1H frequency dimension or
      from the J-scaled doublets along the 15N frequency dimension.

PMID- 11444938
TI  - Precision measurement of the quadrupole coupling and chemical shift tensors of
      the deuterons in alpha-calcium formate.
AB  - Using calcium formate, alpha-Ca(DCOO)2, as a test sample, we explore how
      precisely deuteron quadrupole coupling (QC) and chemical shift (CS) tensors Q and
      sigma can currently be measured. The error limits, +/-0.09 kHz for the components
      of Q and +/-0.06 ppm for those of sigma, are at least three times lower than in
      any comparable previous experiment. The concept of a new receiver is described. A
      signal/noise ratio of 100 is realized in single-shot FT spectra. The measurement
      strategies and a detailed error analysis are presented. The precision of the
      measurement of Q is limited by the uncertainty of the rotation angles of the
      sample and that of sigma by the uncertainty of the phase correction parameters
      needed in FT spectroscopy. With a 4-sigma confidence, it is demonstrated for the
      first time that the unique QC tensor direction of a deuteron attached to a carbon
      deviates from the bond direction; the deviation found is (1.2+/-0.3 degrees ).
      Evidence is provided for intermolecular QC contributions. In terms of Q, their
      size is roughly 4 kHz. The deuteron QC tensors in alpha-Ca(DCOO)2 (two
      independent deuteron sites) are remarkable in three respects. For deuterons
      attached to sp2 carbons, first, the asymmetry factors eta and, second, the
      quadrupole coupling constants C(Q), are unusually small, eta1=0.018, eta2=0.011,
      and C(Q1)=(151.27+/-0.06) kHz, C(Q2)=(154.09+/-0.06) kHz. Third, the principal
      direction associated with the largest negative QC tensor component lies in and
      not, as usual, perpendicular to the molecular plane. A rationalization is
      provided for these observations. The CS tensors obtained are in quantitative
      agreement with the results of an earlier, less precise, line-narrowing multiple
      pulse study of alpha-Ca(HCOO)2. The assignment proposed in that work is
      confirmed. Finally we argue that a further 10-fold increase of the measurement
      precision of deuteron QC tensors, and a 2-fold increase of that of CS tensors,
      should be possible. We indicate the measures that need to be taken.

PMID- 11444939
TI  - Longitudinally detected EPR: improved instrumentation and new pulse schemes.
AB  - A new setup for longitudinal detection (LOD) of EPR signals based on a commercial
      pulse EPR spectrometer equipped with an ENDOR probehead is presented. The design
      is suited for pulse LOD EPR and amplitude-modulated cw LOD EPR experiments. The
      sensitivity is substantially increased compared with earlier designs. Two new
      pulse schemes that take full advantage of the special properties of the setup are
      invented. In transient-nutation longitudinally detected EPR (TN-LOD EPR), the
      nutation of magnetization during a microwave pulse is used to measure the EPR
      signal. In pulse-train excited longitudinally detected EPR (PT-LOD EPR), a train
      of microwave pulses that periodically inverts the magnetization is applied. First
      experimental results on radicals and metal complexes at room temperature are
      presented.

PMID- 11444940
TI  - Improving resolution in fast rotating-frame experiments.
AB  - The rapid rotating-frame technique allows significant reduction in data
      acquisition time compared with the two-dimensional method by stroboscopic
      observation of the nuclear magnetization during its evolution in the rotating
      frame. A onefold reduction in the dimensionality of the original rotating-frame
      experiment is achieved by using a train of strong radiofrequency pulses separated
      by short acquisition windows. The penalty for shortening experimental time is a
      reduction in spectral resolution compared with the two-dimensional method due to
      relaxation of transverse magnetization components during the observation windows.
      A variant of the rapid-rotating frame technique for improving spectral resolution
      based on undersampling and self-phase encoding is presented. An M-fold resolution
      improvement requires M experiments, thus, making possible a tradeoff between
      spectral resolution and experimental time. The technique was applied for spatial
      localization of quadrupole nuclei in powder solids, and resolution improvement is
      demonstrated on one- and two-dimensional NQR images.

PMID- 11444941
TI  - Residual 2H quadrupolar couplings in weakly aligned carbohydrates.
AB  - We report a novel two-dimensional NMR pulse scheme for the 1H-detected
      observation of 2H in isotopically 13C, 2H-enriched carbohydrates. This scheme is
      used for the indirect observation of residual quadrupolar couplings in 13C, 2H
      enriched methyl-beta-D-glucopyranoside weakly aligned in a dilute lyotropic
      liquid-crystalline medium comprising 20% (w/v) dihexanoyl
      phosphatidylcholine/dimyristoyl-phosphatidylcholine (1:3 mol/mol) in D2O. The
      observed residual quadrupolar couplings are substantially larger than residual
      dipolar one-bond 13C-1H couplings under the same experimental conditions. These
      quadrupolar couplings are thus a useful alternative to dipolar couplings for the
      structural analysis of small molecules that align very weakly in dilute liquid
      crystalline media. Moreover, since the quadrupolar coupling constant is very
      uniform throughout endocyclic deuterons of the carbohydrate, these data suggest
      that adoption of a single average value of this parameter in 2H relaxation
      studies on the glycan moieties of glycoproteins and glycopeptides is a valid
      assumption.

PMID- 11444942
TI  - Microscopic imaging of slow flow and diffusion: a pulsed field gradient
      stimulated echo sequence combined with turbo spin echo imaging.
AB  - In this paper we present a pulse sequence that combines a displacement-encoded
      stimulated echo with rapid sampling of k-space by means of turbo spin echo
      imaging. The stimulated echo enables the use of long observation times between
      the two pulsed field gradients that sample q-space completely. Propagators,
      constructed with long observation times, could discriminate slowly flowing
      protons from diffusing protons, as shown in a phantom in which a plug flow with
      linear velocity of 50microm/s could clearly be distinguished from stationary
      water. As a biological application the apparent diffusion constant in
      longitudinal direction of a transverse image of a maize plant stem had been
      measured as a function of observation time. Increasing contrast in the apparent
      diffusion constant image with increasing observation times were caused by
      differences in plant tissue: although the plant stem did not take up any water,
      the vascular bundles, concentrated in the outer ring of the stem, could still be
      discerned because of their longer unrestricted diffusional pathways for water in
      the longitudinal direction compared to cells in the parenchymal tissue. In the
      xylem region of a tomato pedicel flowing water could be distinguished from a
      large amount of stationary water. Linear flow velocities up to 0.67 mm/s were
      measured with an observation time of 180 ms.

PMID- 11444943
TI  - TmDOTA-: a sensitive probe for MR thermometry in vivo.
AB  - The lanthanide complex, thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (TmDOTA-), has been investigated as an agent for MR thermometry
      in vivo. The chemical shifts of the TmDOTA- protons were highly sensitive to
      temperature at a clinically relevant field strength, yet insensitive to pH and
      the presence of Ca2+. Given the excellent stability of lanthanide-DOTA complexes
      and high thermal sensitivity, TmDOTA- is expected to be a good candidate for MR
      thermometry in vivo.

PMID- 11444944
TI  - Theory of FID NMR signal dephasing induced by mesoscopic magnetic field
      inhomogeneities in biological systems.
AB  - A theory of the NMR signal dephasing due to the presence of tissue-specific
      magnetic field inhomogeneities is developed for a two-compartment model. Randomly
      distributed magnetized objects of finite size embedded in a given media are
      modeled by ellipsoids of revolution (prolate and oblate spheroids). The model can
      be applied for describing blood vessels in a tissue, red blood cells in the
      blood, marrow within trabecular bones, etc. The time dependence of the dephasing
      function connected with the spins inside of the objects, s(i), is shown to be
      expressed by Fresnel functions and creates a powder-type signal in the frequency
      domain. The short-time regime of the dephasing function for spins outside the
      objects, s(e), is always characterized by Gaussian time dependence, s(e)
      approximately exp[-zeta(k)(t/tc)2], with zeta being a volume fraction occupied by
      the objects, t(c) being a characteristic dephasing time, and the coefficient k
      depending on the ellipsoid's shape through the aspect ratio of its axes (a/c).
      The long-time asymptotic behavior of s(e) is always "quasispherical"-linear
      exponential in time, s(e) approximately exp(-zetaCt/tc), with the same
      "spherical" decay rate for any ellipsoidal shape. For long prolate spheroids
      (a/c)<<1, there exists an intermediate characteristic regime with a linear
      exponential time behavior and an aspect-ratio-dependent decay rate smaller than
      (zetaC/tc).

PMID- 11444945
TI  - In vivo detection of the cyclic osmoregulated periplasmic glucan of Ralstonia
      solanacearum by high-resolution magic angle spinning NMR.
AB  - We investigate the mobility of the osmoregulated periplasmic glucans of Ralstonia
      solanacearum in the bacterial periplasm through the use of high-resolution (HR)
      NMR spectroscopy under static and magic angle spinning (MAS) conditions. Because
      the nature of periplasm is far from an isotropic aqueous solution, the molecules
      could be freely diffusing or rather associated to a periplasmic protein, a
      membrane protein, a lipid, or the peptidoglycan. HR MAS NMR spectroscopy leads to
      more reproducible results and allows the in vivo detection and characterization
      of the complex molecule.

PMID- 11444946
TI  - A bridged loop-gap S-band surface resonator for topical EPR spectroscopy.
AB  - The design and structure of a bridged loop-gap surface resonator developed for
      topical EPR spectroscopy and imaging of the distribution and metabolism of spin
      labels in in vivo skin is reported. The resonator is a one-loop, one-gap bridged
      structure. A pivoting single loop-coupling coil was used to couple the microwave
      power to the loop-gap resonant structure. A symmetric coupling circuit was used
      to achieve better shielding and minimize radiation. The frequency of the
      resonator can be easily adjusted by trimming the area of the capacitive foil
      bridge, which overlaps the gap in the cylindrical loop. The working frequency set
      was 2.2 GHz and the unloaded Q was 720. The B1 field of this resonator was
      measured and spatially mapped by three-dimensional EPR imaging. The resonator is
      well suited to topical measurements of large biological subjects and is readily
      applicable for in vivo measurements of free radicals in human skin.

PMID- 11444947
TI  - Slow-down of 13C spin diffusion in organic solids by fast MAS: a CODEX NMR Study.
AB  - One- and two-dimensional 13C exchange nuclear magnetic resonance experiments
      under magic-angle spinning (MAS) can provide detailed information on slow
      segmental reorientations and chemical exchange in organic solids, including
      polymers and proteins. However, observations of dynamics on the time scale of
      seconds or longer are hampered by the competing process of dipolar 13C spin
      exchange (spin diffusion). In this Communication, we show that fast MAS can
      significantly slow down the dipolar spin exchange effect for unprotonated carbon
      sites. The exchange is measured quantitatively using the centerband-only
      detection of exchange technique, which enables the detection of exchange at any
      spinning speed, even in the absence of changes of isotropic chemical shifts. For
      chemically equivalent unprotonated 13C sites, the dipolar spin exchange rate is
      found to decrease slightly less than proportionally with the sample-rotation
      frequency, between 8 and 28 kHz. In the same range, the dipolar spin exchange
      rate for a glassy polymer with an inhomogeneously broadened MAS line decreases by
      a factor of 10. For methylene groups, no or only a minor slow-down of the
      exchange rate is found.

PMID- 11444948
TI  - Conformation of the glycosidic linkage in a disaccharide investigated by double
      quantum solid-state NMR.
AB  - Double-quantum heteronuclear local field NMR is performed on a sample of a 13C2
      labeled disaccharide, in which the two 13C spins are located on opposite sides of
      the glycosidic linkage. The evolution of the double-quantum coherences is found
      to be consistent with the solid-state conformation of the molecule, as previously
      determined by X-ray diffraction. The dependence of the double-quantum evolution
      on the glycosidic torsional angles is examined by using a graphical molecular
      manipulation program interfaced to a numerical spin simulation module.

PMID- 11444949
TI  - A two-dimensional experiment that separates decoupling sidebands from the main
      peaks.
AB  - Broadband decoupling techniques generate undesirable cycling sidebands. The new
      two-dimensional technique described here allows separation of these sidebands
      from the main peaks by spreading the sideband responses in the indirectly
      detected dimension (F(1)) according to their frequency separations from the
      parent peaks, leaving the main resonances at zero frequency in F(1). This trace
      at zero frequency shows a thousandfold suppression of the residual sidebands,
      making possible the detection of very weak signals from dilute constituents of
      the sample. The experimental results can be displayed as one-dimensional "quiet
      decoupling" spectra without any significant loss of sensitivity. The new
      technique (DESIRE-decoupling sideband resolved spectroscopy) is simple, robust,
      and straightforward to implement.

PMID- 11444950
TI  - Spatial dependence of a differential shading artifact in images from coil arrays
      with reactive cross-talk at 1.5 T.
AB  - Reactive cross-talk causes leakage of the reception signal between neighboring
      coils of a receiver array. We present here experimental and computer-simulated
      NMR images (based upon a simple theory) to show, for an array of two coils, that
      the leakage (or secondary) signal is combined phase sensitively with the primary
      signal in each coil, to produce (in certain geometries) a differential shading
      artifact, manifest as a divot of missing intensity in the image derived from one
      (and only one) of the two coils. The asymmetry of this effect arises from the
      sense of the nuclear precession, and the afflicted coil may be swapped with its
      mate by reversing the direction of the static magnetic field. The artifact
      appears most clearly in transaxial images and is shown to be forbidden in certain
      types of saggital images. In a simplified theory for an array of two meshes
      (i.e., with only two degrees of freedom) the severity of the artifact depends
      upon the normalized coefficient of coupling (denoted eta and related to the cross
      talk in decibels, psi, by psi=-20 log eta.) While the presence of input trap
      circuits in a typical array doubles the degrees of freedom and complicates both
      the circuit theory and the circuit measurements, the cross-talk is nonetheless
      shown to be given by an expression of the form psi=-20 log eta', where the new
      primed parameter eta' embodies the impedance-matching capacitance and the
      resistance of the scanner's preamplifiers, as well as the mutual reactance
      responsible for the cross-talk. The values of cross-talk inferred from the
      computer simulations of the image artifact are somewhat higher (by an estimated 3
      to 6 dB) than those obtained by bench top measurements; but, given that the
      simulations unmistakably reproduce the unique and highly characteristic visual
      appearance of the artifact, the proposed model for its formation is claimed to be
      essentially correct. Finally, it is suggested that the artifact could be
      corrected by means of the filtered, edge-completed, reception profile described
      by Wald and co-workers (Wald et al., Magn. Reson. Med. 34, 433 (1995)).

PMID- 11444951
TI  - The influence of neighborhood size and habitat shape on the accumulation of
      deleterious mutations.
AB  - To examine the impact of genetic neighborhood size and habitat shape on genetic
      load and the accumulation of deleterious mutation, individual-based simulations
      were performed in continuously distributed habitats. The risk of extinction
      increased as both the area of the habitat and the neighborhood size decreased.
      When the neighborhood area became smaller than the habitat area, habitat shape
      also began to influence the risk of extinction by mutation loads, expected time
      to extinction being shorter in longer and narrower habitats than in a square
      habitat. Both the number of homozygous deleterious loci per individual and the
      mutation load in the population increased as the neighborhood size and total
      population size decreased. Neighborhood size and total population size both
      independently affected the average number of homozygous deleterious loci per
      individual. In addition, as the ratio of the long to the short side of the
      rectangle of a habitat increased, the average number of homozygous deleterious
      loci increased. When the areas of the habitats were held constant, the average
      number of homozygous loci and the mutation loads were smallest for a regular
      square and largest for the longest, narrowest habitat. These results suggest that
      the spatial genetic structure of an individual is an important factor in the
      accumulation of deleterious mutations and the risk of extinction by mutation
      meltdown.

PMID- 11444952
TI  - Arrhythmia as a result of poor intercellular coupling in the sinus node: a
      simulation study.
AB  - The effects of reduced intercellular coupling in the sinus node were investigated
      by means of simulations. Coupling was reduced both uniformly, and by introducing
      localized interaction blocks. In either case, model sinus node element networks
      typically splitted into frequency domains. These were defined as groups of
      neighbour elements which all attained the same mean firing frequency. In systems,
      simulating the vicinity of an impulse outlet to the atrium, the sinus node
      elements often splitted into two domains, one slowly firing just inside the
      outlet, and one normally firing large domain in the sinus node interior. This two
      domain situation was analysed using a two-element system. Wenckebach conduction
      and advanced (m:1) exit blocks were seen, together with more odd block patterns
      and slow chaotic rhythms. The two-domain situation appeared also when two
      discrete outlets were considered. The slow domains around each outlet
      synchronized via the atrium. However, if there were some degree of exit block
      through one of the outlets only, brady-tachy like rhythms could be simulated due
      to a re-entrant circuit including both sinus node and atrial tissue. In
      conclusion, poor coupling in the sinus node seems to be sufficient to produce
      most arrhythmias in the sick sinus syndrome

PMID- 11444953
TI  - Simulated sinoatrial exit blocks explained by circle map analysis.
AB  - In an accompanying study, it was seen that most cardiac arrhythmias that were
      simulated during poor intercellular coupling in the sinus node, were the same as
      those obtained in a two-element system in which one element suffered from a
      strong leakage current. This element corresponds to the sinus node periphery and
      is thus the one which feeds the atrium. In this paper, the interior element was
      replaced by a periodic stimulator. The dynamics of the peripheral element is then
      determined by its phase response curve. Phase response curves for sinus node
      elements subject to leakage were simulated for many different amplitudes of
      depolarizing stimuli. Simulations with circle maps based on these curves produced
      the same sequence of progressing levels of exit block as stimulus strength
      decreased, as did the two-element system when coupling strength was reduced. The
      bifurcations of the circle maps leading to the observed rhythms were identified.
      We found that the essential qualities of the phase response curves were
      determined by generally accepted properties of membrane currents. This suggests
      that the observed rhythms and bifurcations are generic.

PMID- 11444954
TI  - When will plant morphology affect the shape of a seed dispersal "kernel"?
AB  - Most models of dispersal assume that plants are point sources. In reality, the
      scale in height over which seed sources are distributed is often of the same
      order as the scale in distance over which most individual seeds are dispersed.
      But is this sufficient to affect the fundamental shapes of dispersal frequency
      distributions? Most published conclusions about the effects of canopy structure
      on dispersal are subjective. A model is developed to explore the consequences of
      plant canopies for the shapes of whole-plant seed dispersal "kernels". The
      canopies were described by simple geometric shapes, while an empirical
      probability density function (PDF) was used for dispersal from a point source. It
      was found that the resulting whole-plant PDF for dispersal distance was almost
      invariably peaked, whereas the PDF for the density of seed rain (as would be
      measured by pitfall traps) could either be peaked or monotonic according to the
      canopy shape, position of seeds in the canopy, and mean dispersal distance. The
      shapes of kernels from whole plants (distributed seed sources) can be very
      different from those derived from a point source under certain circumstances.

PMID- 11444955
TI  - A mechanism of intracellular timing and its cooperation with extracellular
      signals in controlling cell proliferation and differentiation, an amended
      hypothesis.
AB  - Various observations suggest that an intracellular timer is involved in the
      control of cell proliferation and differentiation that supplements control by
      extracellular signaling and depends on quantitative relations between cytoplasm
      and nucleus. To further elucidate the mechanism of this timer, we examined the
      results of experiments with mice in which cell cycle regulating genes were
      inactivated: the inactivation of negative cell cycle regulators extends cell
      proliferation, whereas inactivation of positive regulators decreases cell
      proliferation. We conclude that this is caused in the former case by shortening
      of G1 which decreases the cytoplasmic growth rate per cell cycle, whereas in the
      latter case this rate is increased due to G1 prolongation. This is consistent
      with our hypothesis according to which the cytoplasmic/nuclear ratio must
      increase to a certain level to induce end stage differentiation and cell cycle
      arrest. A new basis of this hypothesis is the fact that end stage differentiation
      requires large quantities of membranous cytoplasmic structures that the cells are
      unable to produce de novo. Embryonic cells, however, possess only few of these
      structures. The only feasible way to multiply these structures is by growing more
      cytoplasm per cell cycle than needed for a doubling so that successively, the
      level of the cytoplasmic/nuclear ratio is reached that is required for
      differentiation. A consequence is that the cytoplasmic growth rate per cell cycle
      determines the number of amplification divisions. We suggest that the
      differentiation signal may be triggered when a differentiation-preventing protein
      (for example Bcl-2) is diluted out by the expansion of cytoplasmic membrane
      structures, thus simultaneously determining the cell size. The intracellular
      timer and extracellular signals cooperate in adjusting cell production to the
      organism's need and in determining when and how the cells respond to
      extracellular signals or transmit extracellular signals.

PMID- 11444956
TI  - Toward quantitative simulation of germinal center dynamics: biological and
      modeling insights from experimental validation.
AB  - As models of immune system dynamics are developed, it is important to validate
      them with specific experimental data in order to understand their shortcomings
      and guide them toward becoming predictive. In this paper, we examine whether a
      particular mathematical model of germinal center dynamics, proposed by Oprea and
      Perelson, can reproduce experimental data from two specific primary responses,
      namely those directed against the haptens 2-phenyl-5-oxazolone and (4-hydroxy-3
      nitrophenyl)acetyl. We develop formulas for estimating response-specific model
      parameters, as well as constraints for validating the model. In addition, we
      outline a general methodology for translating a continuous/deterministic model,
      expressed as a set of ordinary differential equations, into a discrete/stochastic
      framework. This methodology is used to create a new implementation of the Oprea
      and Perelson model that enables comparison with data on individual germinal
      centers. We conclude that while the model can reproduce the average dynamics of
      splenic germinal centers, it is at best incomplete and does not reproduce the
      distribution of individual germinal center behaviors. In addition to suggesting
      possible extensions to the model which can reconcile the dynamics with some
      aspects of the experimental data, we make a number of specific predictions that
      can be tested by in vivo experiments to obtain further insights and validation.

PMID- 11444957
TI  - Universal scaling laws for hierarchical complexity in languages, organisms,
      behaviors and other combinatorial systems.
AB  - There are many complex systems in nature where components, or "words", are
      combined together to make expressions, or "sentences". Such combinatorial systems
      include: (1) human language, where sentences are composed of words; (2) bird
      vocalization, where songs are built from syllables; (3) organisms, where organism
      expressions (e.g. the tonsil) are made out of cells; (4) behavioral repertoire,
      where mammalian behavior consists of a temporal arrangement of muscle
      contractions; (5) universities, where student academic degrees are comprised of
      departmental concentrations; and (6) electronic devices, where the device's
      actions are implemented via strings of button-presses. My central aim here is to
      discover how combinatorial systems accommodate greater numbers of expressions;
      that is, what changes do combinatorial systems undergo when they "say more
      things?" Are there general laws characterizing the properties of combinatorial
      systems as the number of expressions increases? If so, what are they? My main
      result is that, in all the kinds of combinatorial system mentioned above, there
      appear to be general laws describing how combinatorial systems change as they
      become more expressive. In particular, in each of these cases, increase in
      expression complexity (i.e. number of expressions the combinatorial system
      allows) is achieved, at least in part, by increasing the number of component
      types. Each kind of system follows one of two kinds of scaling law. In the first
      kind of scaling law, expression complexity increase is carried out exclusively by
      increasing the number of component types; the number of components per expression
      (i.e. the expression length) remains invariant. This applies to human language
      over history, bird vocalization, organisms in phylogeny and ontogeny, and
      universities. In the second kind of scaling law, expression complexity is
      accomplished by increasing in a law-like manner both the number of component
      types and the expression length. This applies to two cases of the ontogeny of
      language-the development of words and sentences, and the development of phonemes
      and morphemes-and to mammalian behavior. By treating these diverse systems as
      combinatorial systems we, in addition to elucidating general principles
      underlying such systems, gain insight into each kind of system mentioned.

PMID- 11444958
TI  - Quantitative genetics in the age of genomics.

PMID- 11444959
TI  - Host spatial heterogeneity and the spread of vector-borne infection.
AB  - We analyze how spatial heterogeneity in host density affects the advance of
      vector-borne disease. Infection requires vector infestation. The vector spreads
      only between hosts occupying the same neighborhood, and the number of hosts
      varies randomly among neighborhoods. Simulation of a spatially detailed model
      shows that increasing heterogeneity in host abundance reduces pathogen
      prevalence. Clumping of hosts can limit the advance of the vector, which inhibits
      the spread of infection indirectly. Clumping can also increase the chance that
      the pathogen and vector become physically separated during the initial phase of
      the epidemic process. The latter limitation on the pathogen's spread, in our
      simulations, is restricted to small interaction neighborhoods. A mean-field
      model, which does not maintain spatial correlations between sites, approximates
      simulation results when hosts are arrayed uniformly, but overestimates infection
      prevalence when hosts are aggregated. A pair approximation, which includes some
      of the simulation model's spatial correlations, better describes the vector
      infestation frequencies across host spatial dispersions.

PMID- 11444960
TI  - Directed movement of predators and the emergence of density-dependence in
      predator-prey models.
AB  - We consider a bitrophic spatially distributed community consisting of prey and
      actively moving predators. The model is based on the assumption that the spatial
      and temporal variations of the predators' velocity are determined by the prey
      gradient. Locally, the populations follow the simple Lotka-Volterra interaction.
      We also assume predator reproduction and mortality to be negligible in comparison
      with the time scale of migration. The model demonstrates heterogeneous
      oscillating distributions of both species, which occur because of the active
      movements of predators. One consequence of this heterogeneity is increased
      viability of the prey population, compared to the equivalent homogeneous model,
      and increased consumption. Further numerical analysis shows that, on the
      spatially aggregated scale, the average predator density adversely affects the
      individual consumption, leading to a nonlinear predator-dependent trophic
      function, completely different from the Lotka-Volterra rule assumed at the local
      scale.

PMID- 11444961
TI  - Patterns of 2-year population cycles in spatially extended host-parasitoid
      systems.
AB  - Coexisting but temporally separated cohorts of insects with a multiannual life
      cycle may have dissimilar average abundance, resulting in periodically
      fluctuating population density. In the case of the boreal moth genus Xestia with
      a 2-year life cycle and a distinct abundance difference between the two
      coexisting cohorts, empirical results and a simple model suggest that the
      oscillatory dynamics are maintained by interaction with a parasitoid wasp. Here
      we report theoretical results on a spatially extended version of the basic model
      and relate the modeling results to empirical observations. A spatially extended
      model may have domains oscillating in different phases as is the case between
      western and eastern Finnish Lapland. Spatial heterogeneity tends to fix the
      location of phase boundaries. In contrast, spatially homogeneous temporal
      fluctuations tend to synchronize populations in large regions.

PMID- 11444962
TI  - Somatic mutations in organisms with complex life histories.
AB  - A theoretical model is developed of the fate of mutations for organisms with such
      life-history characteristics as indeterminate growth and clonal reproduction. It
      focuses on how the fate of a particular mutant depends on whether it arises
      during mitotic cell division (somatic mutation) or during meiotic cell division
      (meiotic mutation). At gamete production, individuals carrying somatic mutations
      will produce some proportion of gametes reflecting the original, zygotic genotype
      and some proportion reflecting genotypes carrying the somatic mutation. Focusing
      on allele frequencies at gamete production allows the effects of growth and
      clonal reproduction to be summarized. The relative strengths of somatic and
      meiotic mutation can be determined, as well as the conditions under which the
      change in allele frequency due to one is greater than that due to the other.
      Examples from a published demographic study of clonal corals are used to compare
      somatic and meiotic mutation. When there is no selection acting on either type of
      mutation, only a few cell divisions per time unit on average are needed for the
      change in allele frequency due to somatic mutation to be greater, given
      empirically based mutation rates. When somatic selection is added, the most
      dramatic effect is seen with fairly strong negative selection acting against the
      somatic mutation within individuals. In this case, selection within organisms can
      effectively counteract the effects of somatic mutation, and the change in allele
      frequency due to somatic mutations will not be greater than that due to meiotic
      mutations for reasonable numbers of within-generation cell divisions. The
      majority of the mutation load, which would have been due to somatic mutation, is
      purged by selection within the individual organism.

PMID- 11444963
TI  - Nucleotide binding domain 1 of the human retinal ABC transporter functions as a
      general ribonucleotidase.
AB  - Members of the ATP binding cassette (ABC) superfamily are transmembrane proteins
      that are found in a variety of tissues which transport substances across cell
      membranes in an energy-dependent manner. The retina-specific ABC protein (ABCR)
      has been linked through genetic studies to a number of inherited visual
      disorders, including Stargardt macular degeneration and age-related macular
      degeneration (ARMD). Like other ABC transporters, ABCR is characterized by two
      nucleotide binding domains and two transmembrane domains. We have cloned and
      expressed the 522-amino acid (aa) N-terminal cytoplasmic region (aa 854-1375) of
      ABCR containing nucleotide binding domain 1 (NBD1) with a purification tag at its
      amino terminus. The expressed recombinant protein was found to be soluble and was
      purified using single-step affinity chromatography. The purified protein migrated
      as a 66 kDa protein on SDS-PAGE. Analysis of the ATP binding and hydrolysis
      properties of the NBD1 polypeptide demonstrated significant differences between
      NBD1 and NBD2 [Biswas, E. E., and Biswas, S. B. (2000) Biochemistry 39, 15879
      15886]. NBD1 was active as an ATPase, and nucleotide inhibition studies suggested
      that nucleotide binding was not specific for ATP and all four ribonucleotides can
      compete for binding. Further analysis demonstrated that NBD1 is a general
      nucleotidase capable of hydrolysis of ATP, CTP, GTP, and UTP. In contrast, NBD2
      is specific for adenosine nucleotides (ATP and dATP). NBD1 bound ATP with a
      higher affinity than NBD2 (K(mNBD1) = 200 microm vs K(mNBD2) = 631 microm) but
      was less efficient as an ATPase (V(maxNBD1) = 28.9 nmol min(-)(1) mg(-)(1) vs
      V(maxNBD2) = 144 nmol min(-)(1) mg(-)(1)). The binding efficiencies for CTP and
      GTP were comparable to that observed for ATP (K(mCTP) = 155 microm vs K(mGTP) =
      183 microm), while that observed for UTP was decreased 2-fold (K(mUTP) = 436
      microm). Thus, the nucleotide binding preference of NBD1 is as follows: CTP > GTP
      > ATP >> UTP. These studies demonstrate that NBD1 of ABCR is a general
      nucleotidase, whereas NBD2 is a specific ATPase.

PMID- 11444964
TI  - Effects of bilayer thickness on the activity of diacylglycerol kinase of
      Escherichia coli.
AB  - We have developed a procedure for the reconstitution of Escherichia coli
      diacylglycerol kinase (DGK) into phospholipid bilayers containing diacylglycerol
      substrate. When DGK is reconstituted into a series of phosphatidylcholines
      containing monounsaturated fatty acyl chains, activity against dihexanoylglycerol
      (DHG) as a substrate was found to be markedly dependent on the fatty acyl chain
      length with the highest activity in dioleoylphosphatidylcholine [di(C18:1)PC] and
      a lower activity in bilayers with shorter or longer fatty acyl chains. Low
      activities in the short chain phospholipid dimyristoleoylphosphatidylcholine
      [di(C14:1)PC] followed from an increase in the K(m) value for DHG and ATP, with
      no effect on v(max). In contrast, in the long chain lipid
      dierucoylphosphatidylcholine [di(C24:1)PC], the low activity followed from a
      decrease in v(max) with no effect on K(m). In mixtures of two
      phosphatidylcholines with different chain lengths, the activity corresponded to
      that expected for the average chain length of the mixture. Cholesterol increased
      the activity in di(C14:1)PC but slightly decreased it in di(C18:1)PC or
      di(C24:1)PC, effects that could follow from changes in bilayer thickness caused
      by cholesterol.

PMID- 11444965
TI  - Purine nucleoside phosphorylase from Mycobacterium tuberculosis. Analysis of
      inhibition by a transition-state analogue and dissection by parts.
AB  - Purine salvage pathways are predicted to be present from the genome sequence of
      Mycobacterium tuberculosis. The M. tuberculosis deoD gene encodes a presumptive
      purine nucleoside phosphorylase (PNP). The gene was cloned, expressed, purified,
      and found to exhibit PNP activity. Purified M. tuberculosis PNP is trimeric,
      similar to mammalian PNP's but unlike the hexameric Escherichia coli enzyme.
      Immucillin-H is a rationally designed analogue of the transition state that has
      been shown to be a potent inhibitor of mammalian PNP's. This inhibitor also
      exhibits slow-onset inhibition of M. tuberculosis PNP with a rapid, reversible
      inhibitor binding (K(i) of 2.2 nM) followed by an overall dissociation constant
      (K(i)) of 28 pM, yielding a K(m)/K(i) value of 10(6). Time-dependent tight
      binding of the inhibitor occurs with a rate of 0.1 s(-)(1), while relaxation of
      the complex is slower at 1.4 x 10(-)(3) s(-)(1). The pH dependence of the K(i)
      value of immucillin-H to the M. tuberculosis PNP suggests that the inhibitor
      binds as the neutral, unprotonated form that is subsequently protonated to
      generate the tight-binding species. The M. tuberculosis enzyme demonstrates
      independent and equivalent binding of immucilin-H at each of the three catalytic
      sites, unlike mammalian PNP. Analysis of the components of immucillin-H confirms
      that the inhibition gains most of its binding energy from the 9-deazahypoxanthine
      group (K(is) of 0.39 microM) while the 1,4-dideoxy-1,4-iminoribitol binds weakly
      (K(is) of 2.9 mM). Double-inhibition studies demonstrate antagonistic binding of
      9-deazahypoxanthine and iminoribitol (beta = 13). However, the covalent
      attachment of these two components in immucillin-H increases equilibrium binding
      affinity by a factor of >14 000 (28 pM vs 0.39 microM) compared to 9
      deazahypoxanthine alone, and by a factor of >10(8) compared to iminoribitol alone
      (28 pM vs 2.9 mM), from initial velocity measurements. The structural basis for
      M. tuberculosis PNP inhibition by immucillin-H and by its component parts is
      reported in the following paper [Shi, W., Basso, L. A., Santos, D. S., Tyler, P.
      C., Furneaux, R. H., Blanchard, J. S., Almo, S. C., and Schramm, V. L. (2001)
      Biochemistry 40, 8204-8215].

PMID- 11444966
TI  - Structures of purine nucleoside phosphorylase from Mycobacterium tuberculosis in
      complexes with immucillin-H and its pieces.
AB  - A structural genomics comparison of purine nucleoside phosphorylases (PNPs)
      indicated that the enzyme encoded by Mycobacterium tuberculosis (TB-PNP)
      resembles the mammalian trimeric structure rather than the bacterial hexameric
      PNPs. The crystal structure of M. tuberculosis PNP in complex with the transition
      state analogue immucillin-H (ImmH) and inorganic phosphate was solved at 1.75 A
      resolution and confirms the trimeric structure. Binding of the inhibitor occurs
      independently at the three catalytic sites, unlike mammalian PNPs which
      demonstrate negative cooperativity in ImmH binding. Reduced subunit interface
      contacts for TB-PNP, compared to the mammalian enzymes, correlate with the loss
      of the cooperative inhibitor binding. Mammalian and TB-PNPs both exhibit slow
      onset inhibition and picomolar dissociation constants for ImmH. The structure
      supports a catalytic mechanism of reactant destabilization by neighboring group
      electrostatic interactions, transition-state stabilization, and leaving group
      activation. Despite an overall amino acid sequence identity of 33% between bovine
      and TB-PNPs and almost complete conservation in active site residues, one
      catalytic site difference suggests a strategy for the design of transition-state
      analogues with specificity for TB-PNP. The structure of TB-PNP was also solved to
      2.0 A with 9-deazahypoxanthine (9dHX), iminoribitol (IR), and PO(4) to
      reconstruct the ImmH complex with its separate components. One subunit of the
      trimer has 9dHX, IR, and PO(4) bound, while the remaining two subunits contain
      only 9dHX. In the filled subunit, 9dHX retains the contacts found in the ImmH
      complex. However, the region of IR that corresponds to the oxocarbenium ion is
      translocated in the direction of the reaction coordinate, and the nucleophilic
      phosphate rotates away from the IR group. Loose packing of the pieces of ImmH in
      the catalytic site establishes that covalent connectivity in ImmH is required to
      achieve the tightly bound complex.

PMID- 11444967
TI  - Stereospecific interaction of a novel spirosuccinimide type aldose reductase
      inhibitor, AS-3201, with aldose reductase.
AB  - Aldose reductase (AR) is an NADPH-dependent enzyme implicated in diabetic
      complications. AS-3201 [(R)-(-)-2-(4-bromo-2-fluorobenzyl)-1,2,3,4
      tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone] is a
      structurally novel and potent ARI with an inhibitor constant (K(i) = 10(-)(10) M)
      2000-fold lower than that of its optical antipode (S-isomer). To elucidate the
      inhibition modes and the stereochemical differences in their inhibitory
      potencies, we examined the interaction of these R- and S-isomers with AR under
      physiological conditions. Enzyme kinetic analysis, which was performed by using
      physiological substrates at 37 degrees C, showed that both isomers selectively
      act on the E-NADP(+) complex in both the forward and reverse reactions of AR.
      However, fluorometric titration analysis demonstrated that the affinities of the
      isomers for the E-NADP(+) complex are about the same as those for the E-NADPH
      complex and the apoenzyme. These results suggested that the selective binding to
      the E-NADP(+) complex arises from the predominance of this enzyme form during
      steady-state turnover rather than from binding specificity. Both the competition
      with a known active site-directed ARI and the protective effect on AR
      inactivation by N-bromosuccinimide showed that the isomers bind to the active
      site of the enzyme, but the thermodynamic parameters for the binding to AR
      indicated that additional hydrogen bonds and/or van der Waals interactions
      contribute to the energetic stabilization in the E-R-isomer complex. Molecular
      modeling, together with the deductions from spectroscopic studies, suggested that
      the succinimide ring and the 4-bromo-2-fluorobenzyl group of the R-isomer are
      optimally located for formation of a hydrogen-bonding network with AR, and that
      the latter benzyl group is also effective for the differentiation between AR and
      aldehyde reductase (a closely related enzyme).

PMID- 11444968
TI  - Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7
      dioxosebacic acid, an inhibitor that shows dramatic species selectivity.
AB  - 4,7-Dioxosebacic acid (4,7-DOSA) is an active site-directed irreversible
      inhibitor of porphobilinogen synthase (PBGS). PBGS catalyzes the first common
      step in the biosynthesis of the tetrapyrrole cofactors such as heme, vitamin
      B(12), and chlorophyll. 4,7-DOSA was designed as an analogue of a proposed
      reaction intermediate in the physiological PBGS-catalyzed condensation of two
      molecules of 5-aminolevulinic acid. As shown here, 4,7-DOSA exhibits time
      dependent and dramatic species-specific inhibition of PBGS enzymes. IC(50) values
      vary from 1 microM to 2.4 mM for human, Escherichia coli, Bradyrhizobium
      japonicum, Pseudomonas aeruginosa, and pea enzymes. Those PBGS utilizing a
      catalytic Zn(2+) are more sensitive to 4,7-DOSA than those that do not. Weak
      inhibition of a human mutant PBGS establishes that the inactivation by 4,7-DOSA
      requires formation of a Schiff base to a lysine that normally forms a Schiff base
      intermediate to one substrate molecule. A 1.9 A resolution crystal structure of
      E. coli PBGS complexed with 4,7-DOSA (PDB code ) shows one dimer per asymmetric
      unit and reveals that the inhibitor forms two Schiff base linkages with each
      monomer, one to the normal Schiff base-forming Lys-246 and the other to a
      universally conserved "perturbing" Lys-194 (E. coli numbering). This is the first
      structure to show inhibitor binding at the second of two substrate-binding sites.

PMID- 11444969
TI  - Inhibition of beta-amyloid(40) fibrillogenesis and disassembly of beta
      amyloid(40) fibrils by short beta-amyloid congeners containing N-methyl amino
      acids at alternate residues.
AB  - A potential goal in the prevention or therapy of Alzheimer's disease is to
      decrease or eliminate neuritic plaques composed of fibrillar beta-amyloid
      (Abeta). In this paper we describe N-methyl amino acid containing congeners of
      the hydrophobic "core domain" of Abeta that inhibit the fibrillogenesis of full
      length Abeta. These peptides also disassemble preformed fibrils of full-length
      Abeta. A key feature of the inhibitor peptides is that they contain N-methyl
      amino acids in alternating positions of the sequence. The most potent of these
      inhibitors, termed Abeta16-22m, has the sequence NH(2)-K(Me-L)V(Me-F)F(Me-A)E
      CONH(2). In contrast, a peptide, NH(2)-KL(Me-V)(Me-F)(Me-F)(Me-A)-E-CONH(2), with
      N-methyl amino acids in consecutive order, is not a fibrillogenesis inhibitor.
      Another peptide containing alternating N-methyl amino acids but based on the
      sequence of a different fibril-forming protein, the human prion protein, is also
      not an inhibitor of Abeta40 fibrillogenesis. The nonmethylated version of the
      inhibitor peptide, NH(2)-KLVFFAE-CONH(2) (Abeta16-22), is a weak fibrillogenesis
      inhibitor. Perhaps contrary to expectations, the Abeta16-22m peptide is highly
      soluble in aqueous media, and concentrations in excess of 40 mg/mL can be
      obtained in buffers of physiological pH and ionic strength, compared to only 2
      mg/mL for Abeta16-22. Analytical ultracentrifugation demonstrates that Abeta16
      22m is monomeric in buffer solution. Whereas Abeta16-22 is susceptible to
      cleavage by chymotrypsin, the methylated inhibitor peptide Abeta16-22m is
      completely resistant to this protease. Circular dichroic spectroscopy of Abeta16
      22m indicates that this peptide is a beta-strand, albeit with an unusual minimum
      at 226 nm. In summary, the inhibitor motif is that of alternating N-methyl and
      nonmethylated amino acids in a sequence critical for Abeta40 fibrillogenesis.
      These inhibitors appear to act by binding to growth sites of Abeta nuclei and/or
      fibrils and preventing the propagation of the network of hydrogen bonds that is
      essential for the formation of an extended beta-sheet fibril.

PMID- 11444970
TI  - Soluble phosphatidylserine binds to a single identified site in the C2 domain of
      human factor Va.
AB  - Factor V(a) (FV(a)) is a cofactor for the serine protease factor X(a) that
      activates prothrombin to thrombin in the presence of Ca(2+) and a membrane
      surface. FV(a) is a heterodimer composed of one heavy chain (A1 and A2 domains)
      and one light chain (A3, C1, and C2 domains). We use fluorescence, circular
      dichroism, and equilibrium dialysis to demonstrate that (1) the FV C2 domain
      expressed in Sf9 cells binds one molecule of C6PS with a k(d) of approximately 2
      microM, (2) stabilizing changes occur in the FV C2 domain upon C6PS binding, (3)
      the C6PS binding site in the FV C2 domain is located near residue Cys(2113),
      which reacts with DTNB, and (4) binding to a PS-containing membrane is an order
      of magnitude tighter than that to soluble C6PS. Coupled with a recently published
      crystal structure of the C2 domain, these results support a model for the
      mechanism of C2-membrane interaction.

PMID- 11444971
TI  - Two-dimensional infrared correlation spectroscopy as a probe of sequential events
      in the thermal unfolding of cytochromes c.
AB  - The sequential unfolding events of horse, cow, and tuna ferricytochromes c (cyt
      c) as a function of increasing temperature over the range 25-81 degrees C were
      investigated by resolution-enhanced two-dimensional infrared (2D IR) correlation
      spectroscopy. The 2D IR analysis revealed that in the thermal denaturation of the
      two mammalian cyts, the overall sequence of unfolding is similar, with
      denaturation of extended-chain and turn structures occurring prior to unfolding
      of alpha-helices, followed by denaturation of residual stable extended-chain
      structures. In tuna cyt c, denaturation of all extended-chain structures precedes
      the unfolding of alpha-helices. Moreover, in cow cyt c, unfolding of all helical
      components occurs as one cooperative unit, but in horse and tuna cyts c, the
      helical components behave as subdomains that unfold separately, as proposed
      recently by Englander and co-workers for horse cyt c [Bai et al. (1995) Science
      269, 192-197; Milne et al. (1999) J. Mol. Biol. 290, 811-822]. At higher
      temperatures, following the loss of secondary structure, protein aggregation
      occurs in the three cyts c. The data presented here establish that variations in
      the thermal unfolding of cyts c can be associated with specific sites in the
      protein that influence local flexibility yet have little affect on global
      stability. This study demonstrates the power of resolution-enhanced 2D IR
      correlation spectroscopy in probing unfolding events in homologous proteins.

PMID- 11444972
TI  - The plant tRNA 3' processing enzyme has a broad substrate spectrum.
AB  - To elucidate the minimal substrate for the plant nuclear tRNA 3' processing
      enzyme, we synthesized a set of tRNA variants, which were subsequently incubated
      with the nuclear tRNA 3' processing enzyme. Our experiments show that the minimal
      substrate for the nuclear RNase Z consists of the acceptor stem and T arm. The
      broad substrate spectrum of the nuclear RNase Z raises the possibility that this
      enzyme might have additional functions in the nucleus besides tRNA 3' processing.
      Incubation of tRNA variants with the plant mitochondrial enzyme revealed that the
      organellar counterpart of the nuclear enzyme has a much narrower substrate
      spectrum. The mitochondrial RNase Z only tolerates deletion of anticodon and
      variable arms and only with a drastic reduction in cleavage efficiency,
      indicating that the mitochondrial activity can only cleave bona fide tRNA
      substrates efficiently. Both enzymes prefer precursors containing short 3'
      trailers over extended 3' additional sequences. Determination of cleavage sites
      showed that the cleavage site is not shifted in any of the tRNA variant
      precursors.

PMID- 11444973
TI  - Solution structure of an insect-specific neurotoxin from the New World scorpion
      Centruroides sculpturatus Ewing.
AB  - We report the high-resolution solution structure of the 6.3 kDa neurotoxic
      protein CsE-v5 from the scorpion Centruroides sculpturatus Ewing (CsE, range
      southwestern U.S.). This protein is the second example of an Old World-like
      neurotoxin isolated from the venom of this New World scorpion. However, unlike
      CsE-V, which is the first Old World-like toxin isolated and shows both anti
      insect and anti-mammal activity, CsE-v5 shows high specificity for insect sodium
      channels. Sequence-specific proton NMR assignments and distance and angle
      constraints were obtained from 600 MHz 2D-NMR data. Distance geometry and
      dynamical simulated annealing refinements were performed to produce a final
      family of 20 structures without constraint violations, along with an energy
      minimized average structure. The protein structure is well-defined (0.66 and 0.97
      D rmsd for backbone and all heavy atoms, respectively) with a compact hydrophobic
      core and several extending loops. A large hydrophobic patch, containing four
      aromatic rings and other aliphatic residues, makes up a large area of one side of
      the protein. CsE-v5 shows secondary structural features characteristic of long
      chain scorpion toxins: a two and a half-turn alpha-helix, a three-strand
      antiparallel beta-sheet, and four beta-turns. Among the proteins studied to date
      from the CsE venom, CsE-v5 is the most compact protein with nearly 50% of the
      amide protons having long exchange lifetimes, but CsE-v5 is unusual in that it
      has loop structures similar to both Old and New World toxins. Further, it also
      lacks prolines in its C-terminal 14 residues. It shows some important differences
      with respect to CsE-V not only in its primary sequence, but also in its
      electrostatic potential surface, especially around areas in register with
      residues 8, 9, 17, 18, 32, 43, and 57. The loss of anti-mammal activity in CsE-v5
      and the differences in its anti-insect activity compared to that of other
      proteins such as CsE-V, v1, and v3 from this New World scorpion may be related to
      residue variations at these locations.

PMID- 11444974
TI  - Independent movement of the regulatory and catalytic domains of myosin heads
      revealed by phosphorescence anisotropy.
AB  - Inter- and intradomain flexibility of the myosin head was measured using
      phosphorescence anisotropy of selectively labeled parts of the molecule. Whole
      myosin and the myosin head, subfragment-1 (S1), were labeled with eosin-5
      iodoacetamide on the catalytic domain (Cys 707) and on two sites on the
      regulatory domain (Cys 177 on the essential light chain and Cys 154 on the
      regulatory light chain). Phosphorescence anisotropy was measured in soluble S1
      and myosin, with and without F-actin, as well as in synthetic myosin filaments.
      The anisotropy of the former were too low to observe differences in the domain
      mobilities, including when bound to actin. However, this was not the case in the
      myosin filament. The final anisotropy of the probe on the catalytic domain was
      0.051, which increased for probes bound to the essential and regulatory light
      chains to 0.085 and 0.089, respectively. These differences can be expressed in
      terms of a "wobble in a cone" model, suggesting various amplitudes. The catalytic
      domain was least restricted, with a 51 +/- 5 degrees half-cone angle, whereas the
      essential and regulatory light chain amplitude was less than 29 degrees. These
      data demonstrate the presence of a point of flexibility between the catalytic and
      regulatory domains. The presence of the "hinge" between the catalytic and
      regulatory domains, with a rigid regulatory domain, is consistent with both the
      "swinging lever arm" and "Brownian ratchet" models of force generation. However,
      in the former case there is a postulated requirement for the hinge to stiffen to
      transmit the generated torque associated by nucleotide hydrolysis and actin
      binding.

PMID- 11444975
TI  - The rate of lipid transfer during fusion depends on the structure of fluorescent
      lipid probes: a new chain-labeled lipid transfer probe pair.
AB  - A number of fluorescent probes have been used to follow membrane fusion events,
      particularly intermixing of lipids. None of them is ideal. The most popular pair
      of probes is NBD-PE and Rh-PE, in which the fluorescent groups are attached to
      the lipid headgroups, making them sensitive to changes in the surrounding medium.
      Here we present a new assay for monitoring lipid transfer during membrane fusion
      using the acyl chain tagged fluorescent probes BODIPY500-PC and BODIPY530-PE.
      Like the NBD-PE/Rh-PE assay, this assay is based on fluorescence resonance energy
      transfer (FRET) between the donor, BODIPY500, and the acceptor, BODIPY530. The
      magnitude of FRET is sensitive to the probe surface concentration, allowing one
      to detect movement of probes from labeled to unlabeled vesicles during fusion.
      The high quantum yield of fluorescence, high efficiency of FRET (R(o) is
      estimated to be approximately 60 A), photostability, and localization in the
      central hydrophobic region of a bilayer all make this pair of probes quite
      promising for detecting fusion. We have compared this and two other lipid mixing
      assays for their abilities to detect the initial events of poly(ethylene glycol)
      (PEG)-mediated fusion of small unilamellar vesicles (SUVs). We found that the
      BODIPY500/530 assay showed lipid transfer rates consistent with those obtained
      using the DPHpPC self-quenching assay, while lipid mixing rates measured with the
      NBD-PE/Rh-PE RET assay were significantly slower. We speculate that the bulky
      labeled headgroups of NBD-PE and especially Rh-PE molecules hamper movement of
      probes through the stalk between fusing vesicles, and thus reduce the apparent
      rate of lipid mixing.

PMID- 11444976
TI  - Multiple roles of the conserved key residue arginine 209 in neuronal nicotinic
      receptors.
AB  - We have examined the role of a highly conserved arginine (R209), which flanks the
      M1 transmembrane segment of nAChRs, in the biogenesis and function of neuronal
      nAChRs. Point mutations revealed that, in alphaBgtx-sensitive neuronal alpha7
      nAChRs, the conserved arginine is required for the transport of assembled
      receptors to the cell surface. By contrast, R209 does not play any role in the
      transport of assembled alpha-Bgtx-insensitive neuronal alpha3beta4 nAChRs to the
      cell surface. However, a basic residue at this position of alpha3 and beta4
      subunits is necessary for either synthesis, folding, or assembly of alpha3beta4
      receptors. Moreover, electrophysiological experiments revealed that in
      alpha3beta4 receptors the conserved arginine of the alpha3 subunit is involved in
      either coupling agonist binding to the channel or regulating single channel
      kinetics.

PMID- 11444977
TI  - Functional expression of multidrug resistance protein 1 in Pichia pastoris.
AB  - Overexpression of the multidrug resistance-associated protein (MRP1) causes
      multidrug resistance in cultured cells. MRP1 transports a large number of
      glutathione, glucuronide, and sulfate-conjugated organic anions by an ATP
      dependent efflux mechanism. Six other MRP proteins exist (MRP2-7), and mutations
      in some of these genes cause major pathological conditions in humans. A detailed
      characterization of the structure and mechanism of action of these proteins
      requires an efficient expression system from which large amounts of active
      protein can be obtained. We report the expression of a recombinant MRP1 in the
      methylotrophic yeast Pichia pastoris. The protein is expressed in the membrane
      fraction of these cells, as a stable and underglycosylated 165 kDa peptide.
      Expression levels are very high, and 30 times superior to those seen in multidrug
      resistant HeLa/MRP1 transfectants. MRP1 expressed in P. pastoris binds 8
      azido[alpha-(32)P]ATP in a Mg(2+)-dependent and EDTA-sensitive fashion, which can
      be competed by a molar excess of ADP and ATP. Under hydrolysis conditions (at 37
      degrees C), orthovanadate induces trapping of the 8-azido[alpha-(32)P]nucleotide
      in MRP1, which can be further modulated by known MRP1 ligands. MRP1 is also
      labeled by a photoactive analogue of rhodamine 123 (IAARh123) in P. pastoris/MRP1
      membranes, and this can be competed by known MRP1 ligands. Finally, MRP1-positive
      membrane vesicles show ATP-dependent uptake of LTC(4). Thus, MRP1 expressed in P.
      pastoris is active and shows characteristics of MRP1 expressed in mammalian
      cells, including drug binding, ligand-modulated formation of the MRP1-MgADP-P(i)
      intermediate (ATPase activity), and ATP-dependent substrate transport. The
      successful expression of catalytically active and transport-competent MRP1 in P.
      pastoris should greatly facilitate the efficient production and isolation of the
      wild type or inactive mutants of MRP1, or of other MRP proteins for structural
      and functional characterization.

PMID- 11444978
TI  - Turn structures in CGRP C-terminal analogues promote stable arrangements of key
      residue side chains.
AB  - The 37-amino acid calcitonin gene-related peptide (CGRP) is a potent endogenous
      vasodilator thought to be implicated in the genesis of migraine attack. CGRP
      antagonists may thus have therapeutic value for the treatment of migraine. The
      CGRP C-terminally derived peptide [D(31),P(34),F(35)]CGRP(27-37)-NH(2) was
      recently identified as a high-affinity hCGRP(1) receptor selective antagonist.
      Reasonable CGRP(1) affinity has also been demonstrated for several related
      analogues, including [D(31),A(34),F(35)]CGRP(27-37)-NH(2). In the study presented
      here, conformational and structural features in CGRP(27-37)-NH(2) analogues that
      are important for hCGRP(1) receptor binding were explored. Structure-activity
      studies carried out on [D(31),P(34),F(35)]CGRP(27-37)-NH(2) resulted in
      [D(31),P(34),F(35)]CGRP(30-37)-NH(2), the shortest reported CGRP C-terminal
      peptide analogue exhibiting reasonable hCGRP(1) receptor affinity (K(i) = 29.6
      nM). Further removal of T(30) from the peptide's N-terminus greatly reduced
      receptor affinity from the nanomolar to micromolar range. Additional residues
      deemed critical for hCGRP(1) receptor binding were identified from an alanine
      scan of [A(34),F(35)]CGRP(28-37)-NH(2) and included V(32) and F(37). Replacement
      of the C-terminal amide in this same peptide with a carboxyl, furthermore,
      resulted in a greater than 50-fold reduction in hCGRP(1) affinity, thus
      suggesting a direct role for the amide moiety in receptor binding. The
      conformational properties of two classes of CGRP(27-37)-NH(2) peptides,
      [D(31),X(34),F(35)]CGRP(27-37)-NH(2) (X is A or P), were examined by NMR
      spectroscopy and molecular modeling. A beta-turn centered on P(29) was a notable
      feature consistently observed among active peptides in both series. This turn led
      to exposure of the critical T(30) residue to the surrounding environment.
      Peptides in the A(34) series were additionally characterized by a stable C
      terminal helical turn that resulted in the three important residues (T(30),
      V(32), and F(37)) adopting consistent interspatial positions with respect to one
      another. Peptides in the P(34) series were comparatively more flexible at the C
      terminus, although a large proportion of the [D(31),P(34),F(35)]CGRP(27-37)-NH(2)
      calculated conformers contained a gamma-turn centered on P(34). These results
      collectively suggest that turn structures at both the C-terminus and N-terminus
      of CGRP(27-37)-NH(2) analogues may help to appropriately orient critical residues
      (T(30), V(32), and F(37)) for hCGRP(1) receptor binding.

PMID- 11444979
TI  - Influence of the bovine seminal plasma protein PDC-109 on the physical state of
      membranes.
AB  - PDC-109 is the main component of bovine seminal plasma and has been suggested to
      play an important role in the genesis of bovine sperm cells. Here, the effect of
      binding of PDC-109 to membranes on the structure and physical properties of the
      lipid phase was investigated. For that, ESR measurements were undertaken on model
      membranes (lipid vesicles) and on biological membranes (epididymal spermatozoa)
      by employing various spin-labeled phospholipids. We found that PDC-109 alters the
      membrane structure of lipid vesicles as well as of bovine epididymal spermatozoa
      in that the mobility of spin-labeled phospholipids was reduced in the presence of
      the protein. This immobilizing effect of the protein was not restricted to
      analogues of phosphatidylcholine but was also detected with spin-labeled
      phosphatidylethanolamine. However, the extent of immobilization was lower for
      phosphatidylethanolamine compared with phosphatidylcholine, supporting the lipid
      headgroup specificity of the protein. Besides phospholipid headgroups, the
      physical state of membrane lipids is also important for the interaction of PDC
      109 with membranes, in that, e.g., the immobilizing effect of the protein on
      labeled lipids was larger in membranes above the phase transition temperature
      compared with the effect below this temperature. The results are of relevance for
      understanding the physiological role of PDC-109 in the genesis of sperm cells.

PMID- 11444980
TI  - Kinetic studies of guinea pig liver transglutaminase reveal a general-base
      catalyzed deacylation mechanism.
AB  - Guinea pig liver transglutaminase (TGase) reacts with 0.1 mM N-Cbz-L-Glu(gamma-p
      nitrophenyl ester)Gly (5, prepared herein, K(M) = 0.02 mM) to undergo rapid
      acylation that can be followed spectrophotometrically at 400 nm (pH 7.0, 25
      degrees C). Deacylation of the transiently formed thiolester acyl enzyme
      intermediate via catalytic aminolysis was studied in the presence of six primary
      amines of widely varying basicity (pK(NH+) = 5.6-10.5). Steady-state kinetic
      studies were performed to measure k(cat) and K(M) values for each amine
      substrate. A Bronsted plot constructed through the correlation of
      log(k(cat)/K(M)) and pK(NH+) for each amine substrate displays a linear free
      energy relationship with a slope beta(nuc) = -0.37 +/- 0.08. The shallow negative
      slope is consistent with a general-base-catalyzed deacylation mechanism in which
      a proton is removed from the amine substrate during its rate-limiting
      nucleophilic attack on the thiolester carbonyl. Kinetic isotope effects were
      measured for four acceptor substrates (water, kie = 1.1 +/- 0.1;
      aminoacetonitrile, kie = 5.9 +/- 1.2; glycine methyl ester, kie = 3.4 +/- 0.7; N
      Ac-L-lysine methyl ester, kie = 1.1 +/- 0.1) and are consistent with a proton in
      flight at the rate-limiting transition state. The active site general-base
      implicated by these kinetic results is believed to be His-334, of the highly
      conserved TGase Cys-His-Asp catalytic triad.

PMID- 11444981
TI  - Biotin synthase contains two distinct iron-sulfur cluster binding sites: chemical
      and spectroelectrochemical analysis of iron-sulfur cluster interconversions.
AB  - Biotin synthase is an iron-sulfur protein that utilizes AdoMet to catalyze the
      presumed radical-mediated insertion of a sulfur atom between the saturated C6 and
      C9 carbons of dethiobiotin. Biotin synthase (BioB) is aerobically purified as a
      dimer that contains [2Fe-2S](2+) clusters and is inactive in the absence of
      additional iron and reductants, and anaerobic reduction of BioB with sodium
      dithionite results in conversion to enzyme containing [4Fe-4S](2+) and/or [4Fe
      4S](+) clusters. To establish the predominant cluster forms present in biotin
      synthase in anaerobic assays, and by inference in Escherichia coli, we have
      accurately determined the extinction coefficient and cluster content of the
      enzyme under oxidized and reduced conditions and have examined the equilibrium
      reduction potentials at which cluster reductions and conversions occur as
      monitored by UV/visible and EPR spectroscopy. In contrast to previous reports, we
      find that aerobically purified BioB contains ca. 1.2-1.5 [2Fe-2S](2+) clusters
      per monomer with epsilon(452) = 8400 M(-)(1) cm(-)(1) per monomer. Upon
      reduction, the [2Fe-2S](2+) clusters are converted to [4Fe-4S] clusters with two
      widely separate reduction potentials of -140 and -430 mV. BioB reconstituted with
      excess iron and sulfide in 60% ethylene glycol was found to contain two [4Fe
      4S](2+) clusters per monomer with epsilon(400) = 30 000 M(-)(1) cm(-)(1) per
      monomer and is reduced with lower midpoint potentials of -440 and -505 mV,
      respectively. Finally, as predicted by the measured redox potentials, enzyme
      incubated under typical anaerobic assay conditions is repurified containing one
      [2Fe-2S](2+) cluster and one [4Fe-4S](2+) cluster per monomer. These results
      indicate that the dominant stable cluster state for biotin synthase is a dimer
      containing two [2Fe-2S](2+) and two [4Fe-4S](2+) clusters.

PMID- 11444982
TI  - Spectroscopic changes during a single turnover of biotin synthase: destruction of
      a [2Fe-2S] cluster accompanies sulfur insertion.
AB  - Biotin synthase catalyzes the insertion of a sulfur atom between the saturated C6
      and C9 carbons of dethiobiotin. Catalysis requires AdoMet and flavodoxin and
      generates 5'-deoxyadenosine and methionine, suggesting that biotin synthase is an
      AdoMet-dependent radical enzyme. Biotin synthase (BioB) is aerobically purified
      as a dimer of 38.4 kDa monomers that contains 1-1.5 [2Fe-2S](2+) clusters per
      monomer and can be reconstituted with exogenous iron, sulfide, and reductants to
      contain up to two [4Fe-4S] clusters per monomer. The iron-sulfur clusters may
      play a dual role in biotin synthase: a reduced iron-sulfur cluster is probably
      involved in radical generation by mediating the reductive cleavage of AdoMet,
      while recent in vitro labeling studies suggest that an iron-sulfur cluster also
      serves as the immediate source of sulfur for the biotin thioether ring.
      Consistent with this dual role for iron-sulfur clusters in biotin synthase, we
      have found that the protein is stable, containing one [2Fe-2S](2+) cluster and
      one [4Fe-4S](2+) cluster per monomer. In the present study, we demonstrate that
      this mixed cluster state is essential for optimal activity. We follow changes in
      the Fe and S content and UV/visible and EPR spectra of the enzyme during a single
      turnover and conclude that during catalysis the [4Fe-4S](2+) cluster is preserved
      while the [2Fe-2S](2+) cluster is destroyed. We propose a mechanism for
      incorporation of sulfur into dethiobiotin in which a sulfur atom is oxidatively
      extracted from the [2Fe-2S](2+) cluster.

PMID- 11444983
TI  - Aspartyl protease inhibitor pepstatin binds to the presenilins of Alzheimer's
      disease.
AB  - Mutations in the presenilin genes PS1 and PS2 cause early-onset Alzheimer's
      disease by altering gamma-secretase cleavage of the amyloid precursor protein,
      the last step in the generation of Abeta peptide. Ablation of presenilin (PS)
      genes, or mutation of two critical aspartates, abolishes gamma-secretase
      cleavage, suggesting that PS may be the gamma-secretases. Independently,
      inhibition experiments indicate that gamma-secretase is an aspartyl protease. To
      characterize the putative gamma-secretase activity associated with presenilins,
      lysates from human neuroblastoma SH-SY5Y and human brain homogenates were
      incubated with biotin derivatives of pepstatin, followed by immunoprecipitation
      of PS and associated proteins, and biotin detection by Western blotting.
      Precipitation with PS1 antibodies, directed to either N-terminal or loop regions,
      yielded the same 43 kDa band, of apparent molecular mass consistent with that of
      full-length PS1, although it may represent an aspartyl protease complexed with
      PS1. Incubation of cell lysates with pepstatin-biotin, followed by streptavidin
      precipitation and PS1 Western blotting, revealed PS1 fragments and full-length
      protein, indicating that pepstatin-biotin bound to both cleaved and uncleaved
      PS1. Binding could be competed by gamma-secretase inhibitor L-685,458 and could
      not be achieved with a PS1 mutant lacking the two transmembrane aspartates.
      Pepstatin-biotin was also shown to bind to PS2. PS1 was specifically absorbed to
      pepstatin-agarose, with an optimal pH of 6. Binding of pepstatin-biotin to PS1
      from lymphocytes of a heterozygous carrier of pathologic exon 9 deletion was
      markedly decreased as compared to control lymphocytes, suggesting that this PS1
      mutation altered the pepstatin binding site.

PMID- 11444984
TI  - Identification and function of disulfide bridges in the extracellular domains of
      the angiotensin II type 2 receptor.
AB  - The angiotensin II (AngII) receptor family is comprised of two subtypes, type 1
      (AT(1)) and type 2 (AT(2)). Although sharing low homology (only 34%), mutagenesis
      has identified some key residues that are conserved between both subtypes,
      including four extracellular cysteines. Previous AT(1) mutagenesis demonstrated
      that the cysteines form two disulfide bonds, one linking the first and second
      extracellular loops and another connecting the amino terminus to the third
      extracellular loop. The importance of these AT(1) disulfides in ligand binding is
      supported by the effect of dithiothreitol (DTT). DTT breaks disulfide bonds,
      thereby strongly inhibiting ligand binding in AT(1) receptors. Despite retaining
      the same cysteines, AT(2) receptor ligand binding is paradoxically enhanced by
      DTT. Thus, we constructed a series of AT(2) cysteine mutations, either
      individually or paired, to establish the role of the cysteines and the source of
      DTT's effects. The AT(2) cysteine mutants surprisingly confirmed that the
      cysteines form disulfide bonds in the same manner as in the AT(1) subtype.
      However, breaking the AT(2) disulfide bridges yielded two responses. As in AT(1)
      receptors, mutations disrupting the disulfide bond between the first and second
      extracellular loops reduced AT(2) binding by 4-fold. In contrast, mutations
      breaking the disulfide bridge between the amino terminus and the third
      extracellular loop increased AT(2) binding, mimicking DTT's effect on this
      subtype. Further analysis of AT(1)/AT(2) chimeric exchange mutants of these
      domains suggested that the AT(2) amino terminus and third extracellular loop may
      possess latent binding epitopes that are only uncovered after DTT exposure.

PMID- 11444985
TI  - The 1-127 HA2 construct of influenza virus hemagglutinin induces cell-cell
      hemifusion.
AB  - Conformational changes in the HA2 subunit of influenza hemagglutinin (HA) are
      coupled to membrane fusion. We investigated the fusogenic activity of the
      polypeptide FHA2 representing 127 amino-terminal residues of the ectodomain of
      HA2. While the conformation of FHA2 both at neutral and at low pH is nearly
      identical to the final low-pH conformation of HA2, FHA2 still induces lipid
      mixing between liposomes in a low-pH-dependent manner. Here, we found that FHA2
      induces lipid mixing between bound cells, indicating that the "spring-loaded"
      energy is not required for FHA2-mediated membrane merger. Although, unlike HA,
      FHA2 did not form an expanding fusion pore, both acidic pH and membrane
      concentrations of FHA2, required for lipid mixing, have been close to those
      required for HA-mediated fusion. Similar to what is observed for HA, FHA2-induced
      lipid mixing was reversibly blocked by lysophosphatidylcholine and low
      temperature, 4 degrees C. The same genetic modification of the fusion peptide
      inhibits both HA- and FHA2-fusogenic activities. The kink region of FHA2,
      critical for FHA2-mediated lipid mixing, was exposed in the low-pH conformation
      of the whole HA prior to fusion. The ability of FHA2 to mediate lipid mixing very
      similar to HA-mediated lipid mixing is consistent with the hypothesis that
      hemifusion requires just a portion of the energy released in the conformational
      change of HA at acidic pH.

PMID- 11444986
TI  - New insights into the metal center of 3-deoxy-D-arabino-heptulosonate 7-phosphate
      synthase.
AB  - Metal binding properties for a series of metal-substituted forms of 3-deoxy-D
      arabino-heptulosonate 7-phosphate synthase, DAHPS(Tyr), have been followed by UV
      vis and EPR spectroscopy. The results show that there are two metal species
      present at pH = 7.0 and these are coordinated in a distorted metal binding site
      with a mixed nitrogen and oxygen donor atom coordination set. There is no
      spectroscopic evidence for strong M-S interactions in this system at any pH.
      Metal saturation occurs at a substoichiometric ratio of 0.8-0.85 metal/monomer,
      and the binding trends mirror previously published enzyme activity profiles.
      There is a conformational change for CuDAHPS under basic conditions, and
      equivalent protein handling for apoDAHPS leads to apparent loss of metal binding
      ability. Addition of the substrate PEP does not alter the UV-vis spectra, but
      there are small changes in the EPR spectra of CuDAHPS(Tyr). Further addition of
      the substrate analogue A5P has no effect on either spectra. Taken together, these
      results serve to link previous studies on enzyme activity with the recently
      determined X-ray crystal structure for DAHPS(Phe) and represent the first
      detailed spectroscopic characterization of the metal binding properties of
      DAHPS(Tyr).

PMID- 11444987
TI  - Probing the mechanism of insulin fibril formation with insulin mutants.
AB  - The molecular basis of insulin fibril formation was investigated by studying the
      structural properties and kinetics of fibril formation of 20 different human
      insulin mutants at both low pH (conditions favoring monomer/dimer) and at pH 7.4
      (conditions favoring tetramer/hexamer). Small-angle X-ray scattering showed
      insulin to be monomeric in 20% acetic acid, 0.1 M NaCl, pH 2. The secondary
      structure of the mutants was assessed using far-UV circular dichroism, and the
      tertiary structure was determined using near-UV circular dichroism, quenching of
      intrinsic fluorescence by acrylamide and interactions with the hydrophobic probe
      1-anilino-8-naphthalene-sulfonic acid (ANS). The kinetics of fibril formation
      were monitored with the fluorescent dye, Thioflavin T. The results indicate that
      the monomer is the state from which fibrils arise, thus under some conditions
      dissociation of hexamers may be rate limiting or partially rate limiting. The
      insulin mutants were found to retain substantial nativelike secondary and
      tertiary structure under all conditions studied. The results suggest that fibril
      formation of the insulin mutants is controlled by specific molecular interactions
      that are sensitive to variations in the primary structure. The observed effects
      of several mutations on the rate of fibril formation are inconsistent with a
      previously suggested model for fibrillation [Brange, J., Whittingham, J.,
      Edwards, D., Youshang, Z., Wollmer, A., Brandenburg, D., Dodson, G., and Finch,
      J. (1997) Curr. Sci. 72, 470-476]. Two surfaces on the insulin monomer are
      identified as potential interacting sites in insulin fibrils, one consisting of
      the residues B10, B16, and B17 and the other consisting of at least the residues
      A8 and B25. The marked increase in the lag time for fibril formation with
      mutations to more polar residues, as well as mutations to charged residues,
      demonstrates the importance of both hydrophobic and electrostatic interactions in
      the initial stages of fibrillation. A model for insulin fibril formation is
      proposed in which the formation of a partially folded intermediate is the
      precursor for associated species on the pathway to fibril formation.

PMID- 11444988
TI  - DNA cleavage and religation by human topoisomerase II alpha at high temperature.
AB  - A common DNA religation assay for topoisomerase II takes advantage of the fact
      that the enzyme can rejoin cleaved nucleic acids but cannot mediate DNA scission
      at suboptimal temperatures (either high or low). Although temperature-induced DNA
      religation assays have provided valuable mechanistic information for several type
      II enzymes, high-temperature shifts have not been examined for human
      topoisomerase IIalpha. Therefore, the effects of temperature on the DNA
      cleavage/religation activity of the enzyme were characterized. Human
      topoisomerase IIalpha undergoes two distinct transitions at high temperatures.
      The first transition occurs between 45 and 55 degrees C and is accompanied by a 6
      fold increase in the level of DNA cleavage at 60 degrees C. It also leads to a
      loss of DNA strand passage activity, due primarily to an inability of ATP to
      convert the enzyme to a protein clamp. The enzyme alterations that accompany the
      first transition appear to be stable and do not revert at lower temperature. The
      second transition in human topoisomerase IIalpha occurs between 65 and 70 degrees
      C and correlates with a precipitous drop in the level of DNA scission. At 75
      degrees C, cleavage falls well below amounts seen at 37 degrees C. This loss of
      DNA scission appears to result from a decrease in the forward rate of DNA
      cleavage rather than an increase in the religation rate. Finally, similar high
      temperature alterations were observed for yeast topoisomerase II and human
      topoisomerase IIbeta, suggesting that parallel heat-induced transitions may be
      widespread among type II topoisomerases.

PMID- 11444989
TI  - Inhibition of the serotonin 5-HT3 receptor by nicotine, cocaine, and fluoxetine
      investigated by rapid chemical kinetic techniques.
AB  - The 5-HT(3) serotonin receptor plays an important role in regulating
      communication between cells in the central and peripheral nervous systems. It is
      the target of many different therapeutic agents and abused drugs. A rapid
      chemical kinetic method with a time resolution of 10 ms in combination with the
      whole-cell current-recording technique was employed to study the receptor in NIE
      115 mouse neuroblastoma cells. The mechanism of the channel-opening process,
      receptor desensitization, and receptor inhibition by nicotine, cocaine, and
      fluoxetine were investigated. Two different forms of the 5-HT(3) serotonin
      receptor, each with a different desensitization rate, were observed. The
      inhibition of the receptor by nicotine has not previously been reported. Both
      nicotine and cocaine compete with serotonin for the receptor site that controls
      channel opening, with observed dissociation constants of 25 and 7 microM,
      respectively. Fluoxetine (Prozac), a widely used antidepressant, occupies a
      different regulatory site on the receptor with an apparent K(i) value of 244
      microM.

PMID- 11444992
TI  - A tolerance for ambiguity.

PMID- 11444993
TI  - Examination findings and self-reported walking capacity in patients with lumbar
      spinal stenosis.
AB  - BACKGROUND AND PURPOSE: Spinal stenosis is a common, often disabling, condition
      resulting from compression of the cauda equina and nerve roots. This study was
      designed to: (1) characterize the impairments of patients with lumbar spinal
      stenosis (LSS) and (2) to identify predictors of self-reported walking capacity.
      SUBJECTS: Forty-three patients with symptomatic LSS, from 3 specialty clinics,
      were evaluated. Twenty-eight subjects (65%) were female. The subjects' median age
      was 73.6 years (mean=72.4, SD=10.3, range=45.7-90.7), and the median duration of
      low back pain was 24 months (mean=36.6, SD=41.6, range=0-216). METHODS:
      Demographic data, medical history, and information about low back pain and
      symptoms (eg, numbness, tingling, and lower-extremity weakness) were collected
      using a standardized questionnaire and physical examination. RESULTS: Twenty-two
      subjects (51%) had lower-extremity weakness, primarily of the extensor hallucis
      longus muscle. Thirty-five subjects (81%) had absent or decreased neurosensory
      responses (eg, pinprick, vibration, reflexes), and 28 subjects (66%) reported
      that they were unable to walk farther than 2 blocks. Women were more likely than
      men to report difficulties walking, as were subjects with abnormal Romberg test
      scores and those with greater pain during walking. DISCUSSION AND CONCLUSION:
      Pain and balance problems appeared to be the primary factors limiting ambulation
      in our subjects with LSS.

PMID- 11444994
TI  - Quadriceps femoris muscle torques and fatigue generated by neuromuscular
      electrical stimulation with three different waveforms.
AB  - BACKGROUND AND PURPOSE: Neuromuscular electrical stimulation is used by physical
      therapists to improve muscle performance. Optimal forms of stimulation settings
      are yet to be determined, as are possible sex-related differences in
      responsiveness to electrical stimulation. The objectives of the study were: (1)
      to compare the ability of 3 different waveforms to generate isometric
      contractions of the quadriceps femoris muscles of individuals without known
      impairments, (2) to compare muscle fatigue caused by repeated contractions
      induced by these same waveforms, and (3) to examine the effect of sex on muscle
      force production and fatigue induced by electrical stimulation. SUBJECTS: Fifteen
      women and 15 men (mean age=29.5 years, SD=5.4, range=22-38) participated in the
      study. METHODS: A portable battery-operated stimulator was used to generate
      either a monophasic or biphasic rectangular waveform. A stimulator that was
      plugged into an electrical outlet was used to generate a 2,500-Hz alternating
      current. Phase duration, frequency, and on-off ratios were kept identical for
      both stimulators. Participants did not know the type of waveform being used.
      Torque was measured using a computerized dynamometer. A maximal voluntary
      isometric contraction (MVIC) of the right quadriceps femoris muscle set at 60
      degrees of knee flexion was determined during the first session. In each of the 3
      testing sessions, torque of contraction and fatigue elicited by one waveform were
      measured. Order of testing was randomized. Torque elicited by electrical
      stimulation was expressed as a percentage of average MVIC. A mixed-model analysis
      of variance was used to determine the effect of stimulation and sex on strength
      of contraction and fatigue. Bonferroni-corrected post hoc tests were used to
      further distinguish between the effects of the 3 stimulus waveforms. RESULTS: The
      results indicated that the monophasic and biphasic waveforms generated
      contractions with greater torque than the polyphasic waveform. These 2 waveforms
      also were less fatiguing. The torques from the maximally tolerated electrically
      elicited contractions were greater for the male subjects than for the female
      subjects. DISCUSSION AND CONCLUSION: Muscle torque and fatigue of electrically
      induced contractions depend on the waveform used to stimulate the contraction,
      with monophasic and biphasic waveforms having an advantage over the polyphasic
      waveform. All tested waveforms elicited, on average, stronger contractions in
      male subjects than in female subjects when measured as a percentage of MVIC.

PMID- 11444995
TI  - Development of the professional role behaviors survey (PROBES).
AB  - BACKGROUND AND PURPOSE: This study examined the content validity, internal
      consistency, and underlying dimensions of the Professional Role Behaviors Survey
      (PROBES) for its use in future research. METHODS: Using the 26-item PROBES, 253
      clinical managers reported on the direction and magnitude of change in the role
      behaviors of physical therapists following hospital restructuring. RESULTS:
      Descriptive and correlational statistics of the responses indicated that the
      nature of the role behavior changes was consistent with those identified in the
      literature and that the survey instrument had good internal consistency. A
      principal component factor analysis yielded 5 underlying role behavior
      dimensions: "evaluating and planning," "productivity," "interacting,"
      "information sharing," and "administration/clinical." This factor structure was
      found to provide a good fit with role classification schemes and a clear
      differentiation of physical therapist role behaviors. In addition, the finding
      supports viewing the professional role behaviors as a single construct rather
      than as multiple constructs. DISCUSSION AND CONCLUSION: The PROBES was found to
      have good content validity and internal consistency. It provides a useful tool
      for the study of the changing roles of professional practitioners and a link in
      the study of the effect of organizational change on organizational outcomes such
      as job satisfaction and organizational commitment.

PMID- 11444996
TI  - The impact of social and organizational factors on workers' coping with
      musculoskeletal symptoms.
AB  - BACKGROUND AND PURPOSE: Workers with musculoskeletal symptoms are often advised
      to cope with their symptoms by changing their working technique and by using
      lifting equipment. The main objective of this study was to test the hypothesis
      that negative social and organizational factors where people are employed may
      prevent workers from implementing these coping strategies. SUBJECTS AND METHODS:
      A total of 1,567 automobile garage workers (72%) returned a questionnaire
      concerning coping with musculoskeletal symptoms and social and organizational
      factors. RESULTS: When job demands, decision authority, social support, and
      management support related to health, environment, and safety (HES) were used as
      predictor variables in a multiple regression model, coping as the outcome
      variable was correlated with decision authority, social support, and HES-related
      management support (standardized beta=.079,.12, and.13, respectively). When an
      index for health-related support and control was added to the model, it
      correlated with coping (standardized beta=.36), whereas the other relationships
      disappeared. DISCUSSION AND CONCLUSION: Decision authority and social support
      entail health-related support and control that, in turn, influences coping.

PMID- 11444997
TI  - A review of therapeutic ultrasound: effectiveness studies.
AB  - BACKGROUND AND PURPOSE: Therapeutic ultrasound is one of the most widely and
      frequently used electrophysical agents. Despite over 60 years of clinical use,
      the effectiveness of ultrasound for treating people with pain, musculoskeletal
      injuries, and soft tissue lesions remains questionable. This article presents a
      systematic review of randomized controlled trials (RCTs) in which ultrasound was
      used to treat people with those conditions. Each trial was designed to
      investigate the contributions of active and placebo ultrasound to the patient
      outcomes measured. Depending on the condition, ultrasound (active and placebo)
      was used alone or in conjunction with other interventions in a manner designed to
      identify its contribution and distinguish it from those of other interventions.
      METHODS: Thirty-five English-language RCTs were published between 1975 and 1999.
      Each RCT identified was scrutinized for patient outcomes and methodological
      adequacy. RESULTS: Ten of the 35 RCTs were judged to have acceptable methods
      using criteria based on those developed by Sackett et al. Of these RCTs, the
      results of 2 trials suggest that therapeutic ultrasound is more effective in
      treating some clinical problems (carpal tunnel syndrome and calcific tendinitis
      of the shoulder) than placebo ultrasound, and the results of 8 trials suggest
      that it is not. DISCUSSION AND CONCLUSION: There was little evidence that active
      therapeutic ultrasound is more effective than placebo ultrasound for treating
      people with pain or a range of musculoskeletal injuries or for promoting soft
      tissue healing. The few studies deemed to have adequate methods examined a wide
      range of patient problems. The dosages used in these studies varied considerably,
      often for no discernable reason.

PMID- 11444998
TI  - A review of therapeutic ultrasound: biophysical effects.
AB  - Almost 2 decades ago, it was pointed out that physical therapists tended to
      overlook the tenuous nature of the scientific basis for the use of therapeutic
      ultrasound. The purpose of this review is to examine the literature regarding the
      biophysical effects of therapeutic ultrasound to determine whether these effects
      may be considered sufficient to provide a reason (biological rationale) for the
      use of insonation for the treatment of people with pain and soft tissue injury.
      This review does not discuss articles that examined the clinical usefulness of
      ultrasound (see article by Robertson and Baker titled "A Review of Therapeutic
      Ultrasound: Effectiveness Studies" in this issue). The frequently described
      biophysical effects of ultrasound either do not occur in vivo under therapeutic
      conditions or have not been proven to have a clinical effect under these
      conditions. This review reveals that there is currently insufficient biophysical
      evidence to provide a scientific foundation for the clinical use of therapeutic
      ultrasound for the treatment of people with pain and soft tissue injury.

PMID- 11444999
TI  - The effect on endothelial function of vitamin C during methionine induced
      hyperhomocysteinaemia.
AB  - BACKGROUND: Manipulation of total homocysteine concentration with oral methionine
      is associated with impairment of endothelial-dependent vasodilation. This may be
      caused by increased oxidative stress. Vitamin C is an aqueous phase antioxidant
      vitamin and free radical scavenger. We hypothesised that if the impairment of
      endothelial function related to experimental hyperhomocysteinaemia was free
      radically mediated then co-administration of vitamin C should prevent this.
      METHODS: Ten healthy adults took part in this crossover study. Endothelial
      function was determined by measuring forearm blood flow (FBF) in response to
      intra-arterial infusion of acetylcholine (endothelial-dependent) and sodium
      nitroprusside (endothelial-independent). Subjects received methionine (100 mg/Kg)
      plus placebo tablets, methionine plus vitamin C (2 g orally) or placebo drink
      plus placebo tablets. Study drugs were administered at 9 am on each study date, a
      minimum of two weeks passed between each study. Homocysteine (tHcy) concentration
      was determined at baseline and after 4 hours. Endothelial function was determined
      at 4 hours. Responses to the vasoactive substances are expressed as the area
      under the curve of change in FBF from baseline. Data are mean plus 95% Confidence
      Intervals. RESULTS: Following oral methionine tHcy concentration increased
      significantly versus placebo. At this time endothelial-dependent responses were
      significantly reduced compared to placebo (31.2 units [22.1-40.3] vs. 46.4 units
      [42.0-50.8], p < 0.05 vs. Placebo). Endothelial-independent responses were
      unchanged. Co-administration of vitamin C did not alter the increase in
      homocysteine or prevent the impairment of endothelial-dependent responses (31.4
      [19.5-43.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo) CONCLUSIONS: This
      study demonstrates that methionine increased tHcy with impairment of the
      endothelial-dependent vasomotor responses. Administration of vitamin C did not
      prevent this impairment and our results do not support the hypothesis that the
      endothelial impairment is mediated by adverse oxidative stress.

PMID- 11445000
TI  - Vitamin D receptor initiation codon polymorphism influences genetic
      susceptibility to type 1 diabetes mellitus in the Japanese population.
AB  - BACKGROUND: Vitamin D has been shown to exert manifold immunomodulatory effects.
      Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D
      prevents the development of diabetes in the NOD mouse. We studied the association
      between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D
      receptor gene in a Japanese population. We also investigated associations between
      the vitamin D receptor polymorphism and GAD65-antibody (Ab) positivity. We
      carried out polymerase chain reaction-restriction fragment length polymorphism
      analysis in 110 Japanese T1DM patients and 250 control subjects. GAD65 antibodies
      were assessed in 78 patients with T1DM. RESULTS: We found a significantly higher
      prevalence of the F allele / the FF genotype in the patients compared to the
      controls (P = 0.0069 and P = 0.014, respectively). Genotype and allele
      frequencies differed significantly between GAD65-Ab-positive patients and
      controls (P = 0.017 and P = 0.012, respectively), but neither between GAD65-Ab
      negative patients and controls (P = 0.68 and P = 0.66, respectively) nor between
      GAD65-Ab-positive and -negative patients (P = 0.19 and P = 0.16, respectively).
      CONCLUSIONS: Our findings suggest that the vitamin D receptor initiation codon
      polymorphism influences genetic susceptibility to T1DM among the Japanese. This
      polymorphism is also associated with GAD65-Ab-positive T1DM, although the absence
      of a significant difference between GAD65-Ab-negative patients and controls might
      be simply due to the small sample size of patients tested for GAD65 antibodies.

PMID- 11445001
TI  - The velocity of ultrasound in human primary melanoma tissue - implications for
      the clinical use of high resolution sonography.
AB  - BACKGROUND: Ultrasonography with 20 MHz frequency can be used to estimate tumour
      thickness preoperatively in malignant melanoma (MM) of the skin. The vertical
      invasion depth is the single most important prognostic factor for localised MM,
      and its preoperative knowledge would be very useful for the planning of surgical
      procedures. Since ultrasonographic distance measurements directly depend upon the
      tissue specific ultrasound velocity, we determined the ultrasound velocity in
      primary melanoma. RESULTS: Ultrasound velocity was calculated from runtime
      differences of a 20 MHz ultrasound signal along a known distance either through
      water alone or through thick specimens of primary MM. The ultrasound velocities
      varied between 1553 m/s and 1588 m/s with a mean of 1564 m/s in four different MM
      specimens. The analysis of different parts of the specimens showed that the
      variation of the calculated velocities was larger between different specimens
      than within one individual specimen. CONCLUSIONS: The ultrasound velocity in MM
      tissue may be slightly lower than normally assumed, thereby explaining a part of
      the overestimation usually found in sonographic measurement of melanoma invasion
      depth. Additionally, the variation of ultrasound velocity between individual
      tumours may contribute to the impairment of the correlation found between
      sonometry and Breslow's measurement of MM invasion depth. For practical reasons,
      a setting of 1580 m/s will be appropriate for ultrasonography of primary
      malignant melanoma.

PMID- 11445002
TI  - Adult rat otic placode-derived neurons and sensory epithelium express all four
      erbB receptors: a role in regulating vestibular ganglion neuron viability.
AB  - The erbB receptor family consists of erbB1/epidermal growth factor receptor,
      erbB2/neu, erbB3, and erbB4, all of which have been implicated in cell
      proliferation, differentiation, and survival in several tissues. In the nervous
      system, these family members can function in a trophic capacity for certain
      subpopulations of neurons and some types of non-neuronal cells. Vestibular
      sensory epithelial cells and vestibular ganglion neurons are derived from
      ectodermal otic placode and are essential components of the peripheral vestibular
      system, the sensory system for balance. Recent studies in mammals suggest that
      certain ligands of the epidermal growth factor receptor can induce proliferation
      of vestibular sensory epithelial cells. We now show that vestibular ganglion
      neurons and vestibular sensory epithelial cells express all four erbB receptors
      in adult rats. Cultured vestibular ganglion neurons also expressed all four erbB
      family members and were therefore used to analyze the effects of modulating erbB
      signaling on differentiated vestibular ganglion neurons. Transforming growth
      factor-alpha (a ligand for epidermal growth factor receptor) and sensory and
      motor neuron-derived factor (a ligand for erbB3 and erbB4) promoted vestibular
      ganglion neuron viability, whereas epidermal growth factor (another ligand for
      epidermal growth factor receptor) did not. Glial growth factor 2 (another ligand
      for erbB3 and erbB4) and an antibody that blocks erbB2/neu-mediated signaling
      inhibited vestibular ganglion neuron viability. Collectively, these observations
      indicate that erbB signaling regulates the viability of differentiated otic
      placode-derived cells in mammals and suggest that exogenous modulation of erbB
      signaling in peripheral vestibular tissues may prove therapeutically useful in
      peripheral vestibular disorders.

PMID- 11445003
TI  - Regulation of p63 function by Mdm2 and MdmX.
AB  - p63, a p53-related protein, has been shown to activate p53-responsive genes and
      induce apoptosis in certain cell types. In this study, we examined the effects of
      Mdm2 and MdmX proteins on p63 transactivation, apoptosis, and protein levels. The
      isoforms of p63 most structurally similar to p53, p63gamma (p51A) and p63alpha
      (p51B), were chosen for study. Our results confirm earlier reports demonstrating
      that although both p63 isoforms can transactivate p53-responsive promoters and
      induce apoptosis, p63gamma has a stronger transactivation potential and is a more
      potent inducer of apoptosis than is p63alpha. In addition, both Mdm2 and MdmX
      were able to inhibit the transactivation induced by p63gamma and p63alpha.
      However, only Mdm2 overexpression led to a detectable decrease in p63-induced
      apoptosis. Although Mdm2 binding to p53 triggers ubiquitin-mediated proteosome
      degradation, p63 protein levels were unaltered by association with either Mdm2 or
      MdmX. Finally, immunofluorescence experiments showed that both p63 isoforms were
      localized in the nucleus and could be exported when coexpressed with Mdm2 but not
      with MdmX. These findings suggest that both Mdm2 and MdmX can downregulate p63
      transactivation potential; however, only Mdm2 is capable of inhibiting the
      apoptotic function of p63 by removing it from the nucleus.

PMID- 11445004
TI  - Expression of the Ca2+-activated chloride channel genes CLCA1 and CLCA2 is
      downregulated in human colorectal cancer.
AB  - The role of ion channels in carcinogenesis and tumor progression remains unclear.
      We have used suppression subtractive hybridization of mRNA from paired normal
      colon epithelium and tumor, followed by quantitative kinetic RT-PCR, to
      demonstrate that the transcription of two members of a novel Ca(2+)-dependent
      chloride channel family, CLCA1 and CLCA2, was significantly downregulated in
      approximately 80% of colorectal carcinomas. This figure rose to >90% when
      expression was adjusted for tumor cell proliferation. In normal colon epithelium,
      CLCA1 mRNA levels were significantly associated with c-myc transcription but
      became decoupled in the tumor samples. There was no association between CLCA2 and
      either CLCA1 or c-myc mRNA levels. Transcription of both genes in three
      colorectal cancer cell lines, T84, HT29, and Caco2, was barely detectable.
      Illegitimate transcription of CLCA1 was detected in 12 of 15 blood samples taken
      from healthy volunteers, making its use as a marker for the detection of tumor
      spread unreliable. Our results suggest that CLCA1 could specify a new tumor
      suppressor and that, as in breast cancer, CLCA2 may function as a tumor
      suppressor in colorectal cancer.

PMID- 11445005
TI  - Distribution and molecular characterization of mRNA-binding proteins specific to
      the (U)15 region of 3' UTR of the mouse catalase (Cas-1).
AB  - The 3' UTR of the mouse Cas-1 mRNA, encoding the antioxidant enzyme catalase, has
      a U-rich motif that is conserved across species. This motif is an active site for
      complex and dynamic interactions involving RNA-binding proteins. The spatial,
      temporal, and phylogenetic distribution of the Cas-1 3'-UTR U-rich motif-specific
      RNA-binding proteins was evaluated by gel mobility shift and UV cross-linking
      assays. The specific RNA-protein complexes were observed in mouse tissue
      homogenates representing developmental stages as early as day 10 pc and ranged in
      molecular weight from approximately 38 kDa to approximately 52 kDa. These mRNA
      protein complexes appeared in all vertebrate species examined (human, mouse, rat,
      dog, rabbit, chicken, fish, and frog) but not in insects. The approximately 38
      kDa protein was the most prominent protein in vertebrates. The cDNA sequence of
      the mouse approximately 38-kDa protein was obtained by purification of the
      protein, microsequencing, and RT-PCR. The resulting 456-nt sequence, representing
      the partial internal cDNA sequence, and its deduced amino acid sequence were
      similar to the RNA recognition motif (RRM) of a protein superfamily, implicated
      in splicing, stability, localization, and translation of RNAs. Although the
      results suggest that cis element-binding activity could be a cytoplasmic
      regulator of Cas-1 mRNA metabolism, the significance of this binding remains to
      be determined.

PMID- 11445006
TI  - Molecular cloning, expression, localization, and gene organization of PTX1, a
      human nuclear protein that is downregulated in prostate cancer.
AB  - A cDNA, designated PTX1, has been isolated by subtractive hybridization on the
      basis that it is expressed in normal prostate but not in prostate carcinoma. The
      full-length cDNA was subsequently established by 5' and 3' RACE. Nucleotide
      sequence analysis of the 5'- and 3'-RACE clones yielded a composite cDNA of 1327
      bp, which predicted a protein of 377 amino acid residues with a putative nuclear
      import signal (RRLNRKK) at its N terminus. The PTX1 gene was localized to human
      chromosome 12 and was found to be ubiquitously expressed. A segment of the cDNA
      was expressed in E. coli to produce a fragment of the PTX1 protein for the
      generation of specific antibodies. The resulting antibodies detected a 73-kDa
      protein in both nuclear and cytoplasmic extracts of prostate, although the level
      in the cytoplasmic extract was much lower. Using immunohistochemical analysis,
      the PTX1 protein was localized mainly in the nuclei of glandular epithelia of
      normal prostate. The nuclear staining was greatly reduced in prostate carcinoma.
      The gene organization of PTX1 was established by comparing the cDNA sequence with
      the published human genomic sequence.

PMID- 11445007
TI  - Bone morphogenetic protein-2 (BMP-2) signaling to the Col2alpha1 gene in
      chondroblasts requires the homeobox gene Dlx-2.
AB  - To understand the role of Dlx genes in the process of chondrogenesis, we studied
      the expression of Dlx-2 and Dlx-5 mRNAs in a mouse clonal chondroblast cell line,
      TMC23. We also examined the involvement of Dlx2 in the bone morphogenetic protein
      2 (BMP-2) signaling to the type II collagen gene, Col2alpha1, in this cell line.
      In this report, we show that the TMC23 cells express Dlx-2 and Dlx-5 mRNAs, and
      the levels can be upregulated by recombinant BMP-2 at an early stage of
      chondroblast differentiation. Addition of rBMP-2 dramatically increased type II
      collagen expression at both the mRNA and the protein level. Also, rBMP-2
      increased transcription of Col2alpha1, as shown by stimulation of a chondrocyte
      specific Col2alpha1 enhancer. The mechanism involves Dlx-2, as the stimulatory
      effect of rBMP-2 on the Col2alpha enhancer was blocked by an antisense
      oligonucleotide against Dlx-2 mRNA. The rBMP-2 signaling to the Col2alpha1
      enhancer was also blocked by a dominant-negative Smad1 expression vector. These
      data demonstrate that Dlx-2 is a downstream target of the BMP-2 signaling pathway
      in chondroblasts. Therefore, we propose a model in which rBMP-2 stimulates Dlx-2
      expression, which then serves as a necessary transcription factor for Col2alpha1
      gene expression through a chondrocyte-specific enhancer fragment.

PMID- 11445008
TI  - A competitive PCR-based method to measure human fibroblast growth factor receptor
      1-4 (FGFR1-4) gene expression.
AB  - The four members of the fibroblast growth factor receptor (FGFR) family are cell
      surface membrane-spanning tyrosine kinase receptors involved in a wide spectrum
      of biologic processes. Much evidence also indicates that mutations in FGFR genes
      result in several craniosynostotic disorders and chondrodysplasias, and that
      changes in qualitative and quantitative FGFR expression profiles are implicated
      in tumor induction or progression. Here, we describe a precise and reliable
      competitive PCR-based assay to evaluate human FGFR1-4 gene expression. A single
      multispecific synthetic competitive template was designed to amplify FGFR1-4
      homologous stretches and constructed to contain FGFR1/FGFR2/FGFR3/FGFR4/GAPDH
      tandemly arranged forward and reverse primers that allow competition for cDNA
      specific primer annealing. The housekeeping GAPDH transcript was utilized as a
      reference for comparing the expression profiles of different RNA pools. The assay
      herein described allows the comparison of relative FGFR expression levels, both
      within a single RNA pool and among multiple RNA pool samples. The major
      advantages of such a PCR-based approach are its ability to obtain unbiased FGFR
      mRNA expression patterns and to detect transcripts present in low copy number.
      Qualitative and semiquantitative analyses of the FGFR1-4 transcript repertoire in
      mesenchymal- and epithelial-derived primary cell cultures and cell lines
      demonstrated the utility of such a method to investigate the FGFR1-4 functional
      role in FGF signal transduction.

PMID- 11445010
TI  - Stridor and difficult airway in an AIDS patient.
AB  - Kaposi's sarcoma (KS) is the most common malignancy observed in patients with
      acquired immune deficiency syndrome (AIDS). Although KS involves the head and
      neck in AIDS patients, difficult airway due to KS in an AIDS patient has rarely
      been reported in the literature. We report a patient with AIDS and cutaneous KS
      who developed inspiratory stridor and required an emergent tracheostomy. AIDS
      patients with cutaneous KS should have an assessment of the upper airway even in
      the absence of airway-related symptoms. If KS is present in the upper airway,
      fiber optic and/or radiologic studies are indicated to assess the extent of KS,
      and to define the appropriate interventions.

PMID- 11445011
TI  - Metachronous primary carcinomas of the lung in an HIV-infected patient.
AB  - Studies have suggested that human immunodeficiency virus/acquired immune
      deficiency syndrome (HIV/AIDS) patients have an increased risk of developing
      primary lung cancer, with a poor prognosis. We report a 59-year-old HIV
      seropositive man who developed two metachronous primary bronchogenic carcinomas
      with different histologic features. The initial tumor was cured after early
      diagnosis and resection, with subsequent development of a contralateral tumor 6
      years later. The case emphasizes that early diagnosis and treatment of lung
      cancer in HIV/AIDS patients should be sought as they may improve their short-term
      prognosis. However, because of their immunocompromised state, extended survival
      is still limited by a higher likelihood of developing subsequent malignancies.

PMID- 11445012
TI  - Telling the stories of people with AIDS in rural Haiti.
AB  - For 20 years, Hospital Albert Schweitzer (HAS) in Haiti's Artibonite Valley has
      struggled with the evolving acquired immune deficiency syndrome (AIDS) epidemic.
      Initial efforts to confront the disease met numerous obstacles including denial,
      stigmatization, powerlessness, and mistrust. Over time, HAS and local community
      organizations developed a new approach to the AIDS problem. The first step in
      this approach flowed from the founding principle of HAS: Reverence for Life;
      hospital staff and community leaders provided hospice care to people dying of
      AIDS. Caring for people with AIDS and hearing the stories of people with AIDS
      quickly generated sympathy and a personal sense of vulnerability among community
      leaders and created a desire for community human immunodeficiency virus (HIV)
      education and prevention. Using the stories of people with AIDS as a basis, a
      community education program was launched. More than 1,000 church leaders, voodoo
      priests, and schoolteachers were trained. The majority of these leaders returned
      to their communities and started creative and unexpected initiatives to confront
      the AIDS problem.

PMID- 11445013
TI  - AIDS and thrombosis: retrospective study of 131 HIV-infected patients.
AB  - The recent literature contains reports of thrombotic episodes occurring in
      patients with human immunodeficiency virus (HIV) infection and various
      abnormalities predisposing to a hypercoagulable state have also been reported in
      such patients. To study the incidence of thrombosis in patients infected with
      HIV, and to assess the correlation of thrombosis with the degree of
      immunosuppression as well as the association with active illnesses and neoplasms,
      we reviewed the charts of 131 patients, which include all the patients with the
      diagnosis of HIV admitted or seen in the clinic between January 1, 1993, and
      January 1, 1998. The diagnosis of thrombosis was based on documented reports of
      venous plethysmography or venography for deep venous thrombosis and ventilation
      perfusion scan or pulmonary angiography for pulmonary embolus. Risk factors for
      thrombotic disease were evaluated including general risk factors such as family
      history, ambulatory status, medications, and data were also collected regarding
      CD4 cell counts and the presence of concurrent or remote opportunistic
      infections, acquired immune deficiency syndrome (AIDS)-related malignancy or
      other AIDS-related diseases at the time of diagnosis of the thrombotic event. We
      also reviewed the medical literature via MEDLINE and found 45 cases of patients
      with HIV who developed thromboembolic complications. We found thrombotic
      complications in 9 of 37 patients with a CD4 count less than 200 cells/mm3 and in
      1 of the remaining 94 patients with a CD4 count more than 200 cells/mm3. The
      difference was significant, with p = 0.00004, and the estimated odds of an event
      given CD4 cell counts less than 200/mm3 is 29.89 (95% confidence interval). Three
      patients had abnormalities of anticoagulation proteins. There was a history of
      opportunistic infections in 5 patients and malignancy in 3 patients. Two patients
      with autoimmune hemolytic anemia (AIHA) secondary to HIV-infection developed PE
      upon transfusion of packed red blood cells. The results of this study suggests
      that AIDS appears to predispose to thrombosis. It also revealed a significant
      correlation between thrombotic disease and CD4 counts (<200/mm3) as well as the
      presence of opportunistic infections, AIDS-related neoplasms, or autoimmune
      disorders associated with HIV such as AIHA. Therefore, clinicians caring for
      these patients should be aware of thromboembolic disease as a possible
      complication of AIDS. Further studies to elucidate the mechanisms underlying this
      abnormal hemostatic profile, the epidemiology, and to answer several questions
      such as should patients with risk factors for HIV infection who develop
      thromboembolic complications be further evaluated including tests for HIV are
      warranted.

PMID- 11445014
TI  - Toward a definition of HIV expertise: a survey of experienced HIV physicians.
AB  - Medical care for human immunodeficiency virus (HIV)-infected persons has grown
      increasingly complex, yet few studies have examined experienced HIV physicians'
      views about current HIV medical care. The objective of this study was to examine
      the relationship between physicians' HIV experience, self-perceived expertise,
      and confidence with providing 18 aspects of HIV medical care and between
      confidence in aspects of care and medical specialty. At geographically diverse,
      HIV continuing medical education programs conducted in the fall of 1999, 359
      currently practicing HIV physicians completed a written survey measuring
      participants' demographic characteristics, experience, HIV expertise, and level
      of confidence providing essential aspects of HIV care. Participants currently
      managed a median of 50 HIV-infected patients with a career total of 300.
      Significant correlations were found between experience and expertise items and
      experience and 15 of 18 confidence items. Confidence levels varied from 11% to
      85% highly confident across 18 aspects of HIV care. Physicians' confidence with
      providing aspects of HIV care varied by the three predominant specialty groups
      (infectious diseases, internal medicine, and family practice/general medicine).
      Physicians who have informally specialized in HIV care reported a range of self
      perceived expertise and confidence, indicating the complexity of HIV medical care
      today. Our results suggest that even the most experienced HIV physicians in the
      United States continue to benefit from more experience and that each medical
      specialty examined in this study brings its own set of skills needed to provide
      optimal HIV care. This study constitutes a first step toward defining and
      formalizing HIV medical care.

PMID- 11445015
TI  - Factors affecting health status in African Americans living with HIV/AIDS.
AB  - This study surveyed face-to-face 111 African American newly diagnosed and living
      with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS)
      from the Washington D.C. area, to ascertain the use of, and need for, early
      intervention services. The survey instrument included sections on demographics,
      level of health functioning and health indicators, social and financial support,
      and needed services. This article constructs a health status proxy variable from
      survey items and examines its relationship to biological and social variables.
      Variables found to have a significant relationship with health status are gender,
      type of health insurance, employment, receiving Social Security Disability
      Income, and level of education. A log-linear model for selection of parsimony
      found that the type of health insurance was most highly predictive of health
      status, when controlling for other variables. Persons who receive Medicaid report
      no better levels of health status than those without health insurance. Having
      private health insurance is associated with a 5.3-fold greater chance of having
      good or excellent health status.

PMID- 11445016
TI  - HAART regimens difficult to follow.

PMID- 11445017
TI  - New approach for chlamydia.

PMID- 11445018
TI  - Institute of medicine report validates the science of sex differences.

PMID- 11445020
TI  - Women, men, and pain.

PMID- 11445021
TI  - Toward optimal health: the experts discuss rheumatoid arthritis.

PMID- 11445022
TI  - Unilateral extremity swelling in female patients with cancer.
AB  - Unilateral extremity swelling may be secondary to two major causes in female
      patients with cancer, deep venous thrombosis (DVT) and lymphedema. In women of
      all ages, DVT is high on the differential diagnosis list for unilateral extremity
      swelling. However, in women with an underlying malignancy, DVT and lymphedema
      must both be considered. Appropriate diagnosis and treatment are necessary to
      improve the quality of life and function of the female patient with cancer.

PMID- 11445023
TI  - Sex of first child and breast cancer survival in young women.
AB  - Two studies have reported that young women with breast cancer face increased risk
      of early mortality if their first child was male rather than female. An
      immunological mechanism has been suggested. We sought to confirm these results in
      a larger, historical cohort study of 223 parous women who were aged <45 years at
      breast cancer diagnosis during 1983-1987. Subjects were identified through the
      Maine Cancer Registry. Follow-up data were obtained from hospitals, physicians,
      and death certificates. Reproductive history data were obtained from the next of
      kin of the deceased women, birth certificates, physicians, hospitals, and lastly,
      subjects. With a 7-year follow-up, multivariate modeling found a lower mortality
      risk in women with a male first child (hazard ratio [HR] 0.51, 95% confidence
      interval [CI] 0.32-0.81, log-rank comparison). The survival advantage remained
      for at least 13 years in women with a male firstborn. Thus, previous studies were
      not confirmed. Mortality risk in young women with breast cancer is not increased
      by having borne a male first child rather than a female first child.

PMID- 11445024
TI  - Restless legs syndrome and sleep disturbance during pregnancy: the role of folate
      and iron.
AB  - Restless legs syndrome (RLS) is a neurosensory disorder that typically begins in
      the evening and often prevents a person from falling asleep. It has been
      associated with iron deficiency anemia and dopaminergic pathways and is often
      treated with iron infusion or dopamine agonists. The purpose of this secondary
      analysis of longitudinal data collected on women before, during, and after
      pregnancy is to document the prevalence of RLS during pregnancy, contrast its
      effect on sleep and mood state, and explore the role of folate and iron in the
      expression of RLS, specifically during the third trimester when the syndrome is
      most distressing. The prevalence increased from 0 during preconception to 23% (n
      = 7) during the third trimester of pregnancy. Only 1 subject continued to
      experience RLS after delivery. Compared with those without complaints of restless
      legs, those with restless legs had low serum ferritin at preconception and
      significantly lower folate levels during preconception and at each trimester. In
      addition, time to sleep onset was significantly delayed and depressed mood was
      significantly higher in the RLS group. Rather than indicators of iron deficiency
      anemia (serum ferritin, serum iron, and hemoglobin) or pernicious anemia (vitamin
      B(12)), it was reduced serum folate level that was associated with RLS in this
      sample of pregnant women. Findings indicate a need to reconsider recommendations
      about the normal ranges of serum ferritin and serum folate levels during
      pregnancy to minimize the complaints of restless legs and promote more
      consolidated sleep and better daytime mood state during pregnancy.

PMID- 11445025
TI  - Why do older women discontinue hormone replacement therapy?
AB  - Postmenopausal women who choose hormone replacement therapy (HRT) often
      discontinue this therapy within 1 year. Few studies have considered why older
      women (aged > or =65 years) discontinue therapy. To investigate this question and
      its relationship to HRT-related side effects, we analyzed data collected during
      the 3-month open-label (active HRT and alendronate placebo) run-in phase of a
      clinical trial for osteoporosis prevention and treatment in older women. Among
      women discontinuing the trial, we ascertained a primary reason based on the
      patients' records and classified it as related or unrelated to HRT. The incidence
      of specific HRT-related side effects reported during the run-in phase was
      abstracted from the trial database and compared between patients continuing in
      the trial and those discontinuing for HRT-related reasons. Of the 485 women who
      began the 3-month run-in phase, 112 (23%) discontinued the trial. Specifically,
      73 (15%) women discontinued for reasons considered HRT related. Breast
      swelling/tenderness (26 women) and bloating (9 women) were more often primary
      reasons for discontinuation than were bleeding or spotting (7 women). Comparing
      all reported side effects, bloating was more common in women discontinuing
      because of HRT than in women continuing in the trial (18% versus 3%, p < or =
      0.001), whereas other complaints were similar or lower: breast
      swelling/tenderness (59% versus 67%, p > 0.05), bleeding (16% versus 17%, p >
      0.05), spotting (23% versus 41%, p < or = 0.05). Bloating, of which women
      discontinuing complained significantly more often, and breast
      swelling/tenderness, the most frequently cited primary reason for
      discontinuation, may be more important factors than bleeding or spotting in an
      older woman's decision to discontinue HRT.

PMID- 11445026
TI  - Midlife women's attributions about perceived memory changes: observations from
      the Seattle Midlife Women's Health Study.
AB  - Memory changes are of increasing interest as midlife women approach menopause.
      Recent studies of relationships between estrogen and Alzheimer's disease have
      prompted interest in memory experiences around the time of menopause. The purpose
      of this analysis, part of the larger Seattle Midlife Women's Health Study
      (SMWHS), was to describe the types of memory changes women perceived during
      midlife, to describe their attributions about the memory changes, and to describe
      the relationship among these types and attributions of memory changes and age,
      menopausal transition stage, hormone replacement therapy (HRT) use, stress, and
      major life roles. Women (n = 230) with a mean age of 46.7 years, enrolled in the
      SMWHS, described whether they had noticed any changes in their memory, when they
      noticed them first, the nature of the changes, and what they thought were the
      reasons for the changes. Types of memory changes were collapsed into five
      categories, which included difficulty recalling words or numbers, forgetting
      related to everyday behavior, concentration problems, need for memory aids, and
      forgetting events. Six categories describing attributions about the memory
      changes were increased role burden and stress, getting older, physical health,
      menstrual cycle changes/hormones, inadequate concentration, and emotional
      factors. Stress, physical health, and aging as attributions, rather than the
      menstrual cycle or hormone use, were linked to most types of memory change.

PMID- 11445027
TI  - Women's college physical activity and self-reports of physician-diagnosed
      depression and of current symptoms of psychiatric distress.
AB  - It is believed that physical activity is protective against depression. This
      paper investigates the association between women's athletic activity in the
      college and precollege years and physician-diagnosed depression in postcollege
      years. College alumnae (n = 3940), former college athletes and nonathletes,
      completed a detailed self-administered questionnaire that sought information on
      health histories up to the present time, including questions on history of
      physician-diagnosed depression and current symptoms of psychiatric distress. A
      negative association between college athletic activity and self-reported
      physician-diagnosed depression in the last 10 years was observed (adjusted odds
      ratio [OR] = 0.664, with 95% confidence limits [CL] 0.545, 0.808, p < 0.0001).
      Other factors significantly associated with depression are living with a spouse,
      at time of reporting-protective; self-rated current health good to poor compared
      with very good or excellent; alcoholism; and having a doctoral degree-risk
      factors. Current state variables based on the Rand Mental Health Inventory-5
      (RMHI-5) were also more favorable among athletes. This is the first study to
      report a long-term beneficial association between women's college athletic
      activity and self-reported physician-diagnosed depression in the postcollege
      years and current symptoms of psychiatric distress. The findings support the
      Surgeon General's promotion of the health benefits of physical activity.

PMID- 11445029
TI  - Women's health literaturewatch.

PMID- 11445028
TI  - Sexual orientation and HIV infection prevalence among young Latino injection drug
      users in Harlem.
AB  - Among injection drug users (IDUs), those at highest risk for HIV infection
      include Latinos, young women, and young men who have sex with men (homosexual
      men). We examined how HIV infection prevalence is affected by gender and sexual
      orientation among young Latino IDUs in New York City. We used baseline data from
      a cohort study of young (18-30 years) IDUs in Harlem, New York City, conducted
      from 1997 through 1999. Participants were asked about drug use and sexual
      behaviors, and blood was taken for HIV, hepatitis B, and hepatitis C viral
      antibody testing. Of 156 participants who self-identified as Latino, 145 (94%)
      were Puerto Rican. Overall, 101 (65%) were heterosexual men, 11 (7%) were men who
      have sex with men (MSM), 32 (20%) were heterosexual women, and 12 (8%) were women
      who have sex with women (WSW). Of the whole cohort, 17 (11%) were HIV positive.
      HIV infection rates were higher among WSW (42%, p < 0.05), heterosexual women
      (16%, p < 0.05), and homosexual men (18%, p = 0.09) than heterosexual men (5%).
      Compared with heterosexual men, homosexual men were significantly (p < 0.05) more
      likely to have received money or drugs for sex (64% versus 33%), and WSW were
      significantly more likely to have had unprotected sex with an IDU 5 years or more
      older (50% versus 16%). Multivariate analysis showed being a WSW (adjusted odds
      ratio [AOR] = 8.68, 95% confidence interval [CI] 1.78-42.26) and having
      unprotected sex with an older IDU (AOR = 7.01, 95% CI 2.23-21.96) to be
      associated with HIV infection. Sexual transmission may account for many HIV
      infections among young Latino IDUs. The high prevalence of HIV infection among
      WSW may, in part, be due to their having unprotected sex with older men, but
      studies with larger sample sizes are needed to confirm this.

PMID- 11445036
TI  - The caregiver's dilemma.

PMID- 11445038
TI  - News from the society for women's health research: working towards a
      comprehensive profile of women's health.

PMID- 11445039
TI  - Observations from the CDC: CDC's Screen for Life: a National Colorectal Cancer
      Action Campaign.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in the
      United States. Despite the availability of several different screening tests for
      colorectal cancer, screening rates remain low. To raise awareness about
      colorectal cancer and encourage men and women aged 50 and older to speak with
      their physicians about being screened for colorectal cancer, the Centers for
      Disease Control and Prevention and the Health Care Financing Administration
      launched Screen for Life: A National Colorectal Cancer Action Campaign in 1999.
      The purpose of this paper is to outline the development of this multiyear,
      multimedia campaign, from conducting formative research to developing campaign
      messages and materials. Limited process evaluation results are presented.

PMID- 11445040
TI  - Toward optimal health: the experts discuss lung cancer in women. Interview by
      Jodi Meisler.

PMID- 11445041
TI  - Eating for energy.

PMID- 11445042
TI  - Exploring the biological contributions to human health: does sex matter?

PMID- 11445043
TI  - Hormonal and barrier methods of contraception, oncogenic human papillomaviruses,
      and cervical squamous intraepithelial lesion development.
AB  - We assessed the influence of hormonal (oral, injectable, or levonorgestrel
      [Norplant, Wyeth-Ayerst, Philadelphia, PA]) and barrier methods of contraception
      on the risk of cervical squamous intraepithelial lesions (SIL), while adjusting
      for high-risk (HR) HPV infection. Subjects were women receiving family planning
      services through the state health department clinics from 1995 to 1998. We
      selected 60 cases with high-grade cervical/SIL (HSIL) and 316 with low-grade
      cervical/SIL (LSIL) and controls (427 women with normal cervical cytology) and
      analyzed cervical DNA for HR-HPV, using Hybrid Capture I (Digene; Gaithersburg,
      MD). When assessing ever use, duration, recency, latency, and age at first use,
      neither oral contraceptives (OC), Norplant, nor injectable use was associated
      with an increased risk of SIL development after adjusting for age, age at first
      sexual intercourse, and HR-HPV positivity. Among HR-HPV-positive women, longer
      duration barrier method use was associated with a reduced risk of SIL. This
      finding has important clinical implications for SIL prevention among HR-HPV
      infected women.

PMID- 11445044
TI  - Adherence to screening guidelines for breast and cervical cancer in
      postmenopausal women with coronary heart disease: an ancillary study of
      volunteers for hers.
AB  - Postmenopausal women with coronary heart disease (CHD) who volunteered for the
      Heart and Estrogen/Progestin Replacement Study (HERS) randomized clinical trial
      had high rates of gynecological abnormalities. We examined compliance with
      gynecological cancer screening and factors affecting this behavior. Women who met
      inclusion criteria for HERS and were seen for screening by the study gynecologist
      were considered eligible for this study. Data were abstracted from study records,
      and additional information was obtained by telephone questionnaire. Adherence to
      mammography, breast examination, pelvic examination, and Pap smear
      recommendations was assessed. Provider behavior and its effect on compliance were
      assessed. Compliance rates were 59.1% for monthly breast self-examination (BSE),
      67.2% for yearly mammography, 73% for yearly Pap smear and pelvic examination,
      and 75.7% for provider breast examination. Over 50% of patients had most of their
      screening tests done within the last year. Provider behavior was significantly
      related to patient screening compliance for mammography, breast examination, Pap
      smear, and pelvic examination. Provider gender was not significantly related to
      adherence. There were no significant differences in compliance rates based on the
      type of most recent coronary event. Compliance rates did not differ significantly
      between patients with and without gynecological abnormalities, except for
      mammography (78.3% versus 48.3%, p = 0.02). The majority of patients were
      compliant with gynecological screening. Among patients with gynecological
      abnormalities, mammography compliance was significantly lower. Provider behavior
      was an important factor in influencing women to obtain preventive screening.
      There were no significant differences in compliance based on provider gender or
      type of coronary event preceding HERS enrollment.

PMID- 11445045
TI  - Body weight and cancer screening among women.
AB  - Obesity increases cancer risk, yet small-scale surveys indicate that obese women
      delay or avoid cancer screening even more so than do nonobese women. We sought to
      estimate the association between body mass index (BMI) (kg/m(2)) and delayed
      cancer screening among adult women in a population-based survey. Subjects were
      women classified by BMI as underweight (<18.5), desirable weight (18.5-24.9),
      overweight (25-29.9), obese class I (30-34.9), obese class II (35-39.9), and
      obese class III (> or =40). Outcome measures were intervals (0 for < or =2 years
      versus 1 for >2 years) since most recent screening for Papanicolaou (Pap) smear,
      mammography, and clinical breast examination (CBE). Adjusting for age, race,
      smoking, and health insurance, we observed J-shaped associations between BMI and
      screening. Compared with desirable weight women, underweight women (odds ratios
      [OR] = 1.21, 95% confidence interval [95% CI] 1.09-1.34), overweight women (OR =
      1.13, 95% CI 1.07-1.18), and obese women (OR range 1.22-1.69) were significantly
      more likely to delay Pap smear testing for >2 years. Underweight (OR = 1.32, 95%
      CI 1.13-1.54), obesity class I (OR = 1.12, 95% CI 1.02-1.23), and obesity class
      III women (OR = 1.32, 95% CI 1.10-1.54) were more likely to delay mammography,
      and overweight (OR = 1.10, 95% CI 1.01-1.19), obesity class I (OR = 1.18, 95% CI
      1.08-1.30), and obesity class III women (OR = 1.47, 95% CI 1.23-1.75) were more
      likely to delay CBE. White women were more likely to delay CBE as a function of
      BMI than were non-white women. Weight may be an important correlate of cancer
      screening behavior, particularly for white women.

PMID- 11445046
TI  - Psychological factors and hyperemesis gravidarum.
AB  - Hyperemesis gravidarum (HG) is a condition of severe, intractable nausea and
      vomiting during pregnancy. It has long been held that HG is a psychosomatic
      illness reflective of a long-term psychological trait, that is, conversion
      disorder. We investigated this possibility by conducting a two-phase study: (1) a
      comparison of women with (n = 9) and without (n = 10) HG during pregnancy and (2)
      a comparison of nonpregnant women who did (n = 10) and did not (n = 12) have HG
      during their most recent pregnancies. The pattern of findings differed between
      experiments 1 and 2. During pregnancy, women with HG scored significantly higher
      on three scales associated with conversion disorder (all p values <0.01) than did
      women without HG. There were no significant differences between HG subjects and
      controls after pregnancy. We find no support for the theory that HG is a
      psychosomatic condition. Rather, it appears to be a complex interaction of
      biological, psychological, and sociocultural factors.

PMID- 11445047
TI  - Breast cancer screening among Chamorro women in southern California.
AB  - Breast cancer is the most common cancer in Pacific Islander women, yet relatively
      little is known about their cancer risks and screening behaviors. Chamorros are
      indigenous people from Guam, and California is home to the largest numbers of
      Chamorros on the mainland United States. This study examined the breast cancer
      risk, knowledge, and screening behaviors in a nonprobability sample of Chamorro
      women age 40 years and older in Los Angeles and Orange Counties (n = 227). The
      proportional incidence ratio for breast cancer among Chamorro women was found to
      be 0.7 compared with white women in California, indicating a lower current breast
      cancer risk for Chamorro women compared with white women. Thirty-seven percent of
      respondents ever performed a breast self-examination (BSE), 93% ever had a
      clinical breast examination (CBE), and 77% ever had a mammogram. In terms of
      screening maintenance, only 27% did BSE monthly, 66% received a CBE in the past
      year, and 25% received yearly mammograms. Significant correlates of CBE were
      higher educational attainment, married status, higher income, and health
      insurance coverage. Women who knew of breast cancer symptoms, would undergo
      treatment, and would like to know if they had breast cancer were also more likely
      to have ever had a CBE. With regard to mammography, older age, moderate income,
      married status, and use of traditional healers and healing practices were
      associated with higher screening incidence. Implications of these findings for
      developing culturally tailored and appropriate cancer screening programs are
      discussed.

PMID- 11445048
TI  - HIV risk behavior and psychological correlates among native American women: an
      exploratory investigation.
AB  - Native American women are at increased risk for HIV infection, but few studies
      have studied this threat. To address this gap in the literature, we assessed HIV
      risk behavior and explored the hypothesized psychological antecedents of risk
      behavior in 53 Native American women. Survey results indicated that women's HIV
      related knowledge was incomplete and many women still held misconceptions about
      HIV. One third of the sample reported having two to five sexual partners in the
      past 5 years, and 30% of the women reported alcohol use prior to sexual
      intercourse. Women who were classified at higher risk, that is, who did not use
      condoms consistently, felt less vulnerable to HIV and were less ready to change
      their risky sexual behaviors compared with their lower-risk counterparts. These
      findings indicate that Native American women are at risk for HIV infection and
      can no longer be neglected by those seeking to prevent HIV infections. Culturally
      congruent and gender-specific interventions that provide information and
      behavioral skills to Native American women as well as increase their motivation
      to adopt safer sexual behaviors are needed.

PMID- 11445049
TI  - Paraneoplastic cerebellar degeneration as the first manifestation of cancer.
AB  - Paraneoplastic cerebellar degeneration (PCD) is a type of paraneoplastic syndrome
      that primarily affects women with gynecological cancers. Patients typically
      experience pancerebellar symptoms, including gait ataxia, dysarthria, nystagmus,
      and truncal and appendicular ataxia. We present the case of a 50-year-old woman
      with PCD and presumed ovarian cancer who initially complained of ataxia and
      dysarthria. PCD was diagnosed on the basis of her symptoms, diagnostic imaging,
      and laboratory work. PCD symptoms may precede the diagnosis of malignancy by
      months or years. Early diagnosis and treatment of these syndromes, including
      rehabilitation, may result in improvements in quality of life for this population
      of patients.

PMID- 11445050
TI  - Women's health literaturewatch.

PMID- 11445056
TI  - Defining and Treating the Metabolic Syndrome: A Primer from the Adult Treatment
      Panel III.

PMID- 11445057
TI  - Atrial Fibrillation.
AB  - The conversion of atrial fibrillation (AF) to normal sinus rhythm should be
      attempted in patients who present with this condition, as long as the cure is not
      worse than the disease itself. In young patients with normal hearts, AF has a
      small impact on morbidity and mortality. The primary indication for conversion in
      this population is often symptoms. In contrast, in patients with diseased hearts
      or who are older than 65 years, maintaining sinus rhythm may have a favorable
      impact on stroke risk, ventricular function, and symptoms. In the absence of
      normal sinus rhythm, these patients should receive anticoagulants. Rate control
      is the preferred first-line strategy for asymptomatic patients and patients
      presenting with a history of long-standing, persistent AF, making conversion and
      maintenance of sinus rhythm unlikely. Rate control may be used in patients who
      develop AF during an acute systemic illness, which will likely terminate with
      time or therapy. Conversion to sinus rhythm should be considered in patients with
      a first episode of AF, as unconverted AF tends to perpetuate itself. Conversion
      can be attempted if the duration of AF is less than 48 hours or if the patient
      has received anticoagulants when the duration is not known. Other indications for
      cardioversion are prolonged episodes in patients with otherwise infrequent
      episodes of paroxysmal AF, and in patients who refuse to take anticoagulants or
      in whom anticoagulation is contraindicated. After the patient is converted to
      sinus rhythm, the decision to initiate chronic drug therapy should be based on
      the presence of other cardiac and medical diseases that increase the risk of
      recurrence and serious symptoms in case of recurrence (such as hypertrophic
      cardiomyopathy or mitral stenosis). It is acceptable to manage patients with new
      onset AF and normal cardiac function with cardioversion alone and not initiate
      chronic antiarrhythmic therapy afterwards. However, in patients with abnormal
      hearts (coronary artery disease, hypertensive or mitral valvular heart disease,
      and cardiomyopathy) AF is likely to recur, and such patients should be placed on
      antiarrhythmic medication.

PMID- 11445058
TI  - Atrial Flutter.
AB  - Atrial flutter (AFl) is an arrhythmia resulting from reentry in a macroreentrant
      circuit, most commonly in the right atrium. Typical AFl uses the narrow isthmus
      of right atrial tissue between the tricuspid valve annulus and the inferior vena
      cava orifice as part of the macroreentrant circuit. The treatment of AFl is
      directed toward achieving the following four goals. 1) In the presence of AFl,
      adequate rate control is required, which can be achieved in most but not all
      patients by oral or intravenous digoxin, calcium channel blockers, or beta
      blockers, alone or in combination. 2) Anticoagulation with warfarin should be
      considered in patients with recurrent AFl, especially those over 70 years of age,
      and those with a history of atrial fibrillation, stroke, or structural heart
      disease. 3) Conversion to sinus rhythm can be achieved in up to 70% of patients
      with intravenous ibutilide, but this should be reserved for patients with either
      normal hearts or only mild left ventricular dysfunction. Direct-current
      cardioversion is nearly 100% effective and is ideal for patients with left
      ventricular dysfunction. 4) Long-term maintenance of sinus rhythm may be achieved
      in up to 50% to 60% of patients by using antiarrhythmic drugs, including sotalol,
      amiodarone, dofetilide, propafenone, and flecainide, but with the potential for
      causing significant proarrhythmia and side effects. Radiofrequency catheter
      ablation may cure over 90% of patients with type 1 AFl (using the tricuspid valve
      to inferior vena cava isthmus), and from 70% to 90% of patients with atypical
      AFl. Newer mapping techniques, such as electroanatomic mapping, are likely to
      further reduce procedure time and improve success rates.

PMID- 11445059
TI  - Bradyarrhythmias.
AB  - In our opinion, the term bradyarrhythmia should be reserved for bradycardias
      (heart rates less than 60) that are associated with symptoms such as syncope or
      near-syncope, congestive heart failure, exercise intolerance, fatigue, or a
      confusional state that improves with resolution of the bradycardia. The mere
      presence of a bradycardia that is not associated with these symptoms almost never
      justifies aggressive intervention, with few notable exceptions. It is important
      to determine if the bradyarrhythmia will not resolve spontaneously or with the
      alleviation of a condition that is the likely cause of the bradyarrhythmia. If a
      hemodynamically stable patient can be observed safely while being treated for a
      metabolic or ischemic condition or an adverse drug reaction, then it is not
      justified to implant a permanent pacemaker, though a temporary pacemaker may be
      necessary in the interim. Certain forms of reflex-mediated syncope have an
      element of inappropriate bradycardia that may be amenable to pacing. Pacemaker
      implantation should be considered for patients with recurrent vasovagal or
      situational syncope that is refractory to other therapies. The treatment of
      specific bradyarrhythmias should be in accordance with the guidelines laid forth
      by the joint councils of the American Heart Association and the American College
      of Cardiology.

PMID- 11445060
TI  - Syncope.
AB  - Successful treatment of patients with syncope depends on the accuracy of the
      diagnosis, because syncope is a symptom, not a disease; diagnosis of the cause
      for syncope therefore creates a blueprint for treatment. Most experienced
      practitioners can diagnose the cause of syncope for less than half of their
      patients. Excessive and repeat testing is expensive and may not improve the
      chance of a correct diagnosis. Patient history is the key to the diagnosis.
      Treatment may vary from a lifestyle change to open heart surgery. The great
      challenge of treating patients with syncope is to provide cost-effective, safe
      therapy to those with a benign course and still provide needed treatment for
      those whose syncope is life threatening.

PMID- 11445061
TI  - Tobacco Smoking in Patients with Cardiovascular Disease.
AB  - Smoking tobacco is a major risk factor for patients with cardiovascular disease
      (CVD). Quitting smoking rapidly reduces the risk for cardiovascular events. The
      majority of patients who smoke express a desire to stop, and cost-effective
      interventions are available. Behavioral (counseling) and pharmacologic (nicotine
      replacement and non-nicotine medications) treatments double or triple the rate of
      long-term cessation and should be offered in combination to all patients with CVD
      who use tobacco. Behavioral therapy can be effectively delivered by a variety of
      health care providers and means (in person, telephone, mail). For patients with
      CVD, more intensive and sustained interventions should be encouraged. Nicotine
      patches have been studied extensively in patients with stable CVD and are safe.
      Bupropion (a non-nicotine aid) also may be especially useful for patients with
      CVD. Special consideration is needed for patients with acute coronary syndromes
      (ie, myocardial infarction and unstable angina). It is important to create a
      clinical environment that supports treatment of patients with nicotine addiction.
      Simple changes in office and hospital routines and procedures (establishing
      routine screening to identify users of tobacco, prompts to encourage
      intervention, establishing links to more intensive nicotine-dependence treatment
      programs) can substantially improve the identification, treatment, and outcomes
      for patients with CVD who use tobacco.

PMID- 11445062
TI  - Syndrome X.
AB  - The manifestations of syndrome X increase the risk of coronary heart disease
      (CHD) as much, if not more so, than elevated low-density lipoprotein (LDL)
      cholesterol concentrations. The fundamental abnormality leading to the
      manifestations that comprise syndrome X is resistance to insulin regulation of
      muscle glucose uptake and adipose tissue lipolysis. To prevent decompensation of
      glucose tolerance, patients with syndrome X secrete large amounts of insulin.
      Treatment should be aimed at 1) increasing insulin sensitivity, 2) attenuating
      day-long hyperinsulinemia, and 3) pharmacologic treatment of the specific
      manifestations of syndrome X if lifestyle interventions are not entirely
      successful. The two major lifestyle modulators of insulin action are body weight
      and physical fitness--the heavier and the more sedentary a patient is, the
      greater the degree of insulin resistance and compensatory hyperinsulinemia. In
      overweight, insulin-resistant patients, the magnitude of insulin resistance is
      attenuated with weight loss (10 to 15 pounds). Aerobic exercise (30 minutes a
      session, three to four times a week) is equally effective, irrespective of the
      presence of obesity. In the absence of associated weight loss, the usually
      recommended low-fat, high-carbohydrate diet makes the manifestations of syndrome
      X worse. This is because the more carbohydrates present in the insulin-resistant
      patient's diet, the greater the insulinogenic stimulus to the pancreas, and hence
      day-long plasma insulin levels are higher. Replacing saturated fat with
      monounsaturated and polyunsaturated fat instead of carbohydrates provides the
      same favorable effect on LDL cholesterol concentrations without the insulin
      stimulating effect of low-fat, high-carbohydrate diets. This intervention does
      not affect insulin resistance, but maintains day-long insulin levels as low as
      possible. Although lifestyle changes can be very effective in attenuating the
      manifestations of syndrome X, it may be necessary to initiate pharmacologic
      treatment aimed at controlling dyslipidemia and hypertension. The major obstacle
      to reducing the risk of CHD in patients with syndrome X is becoming aware of its
      manifestations. After this is accomplished, the relatively simple approaches
      outlined herein are an effective treatment strategy.

PMID- 11445063
TI  - Hypertension.
AB  - Controlled multicenter clinical trials and almost 50 years of clinical experience
      have demonstrated incontrovertibly the efficacy, safety, and feasibility of
      antihypertensive pharmacotherapy. In addition, this vast clinical record has
      shown, through the intrinsic ability of antihypertensive therapy to control
      arterial pressure, how to prevent and reverse many of the complications of
      hypertensive cardiovascular disease affecting the major target organs of the
      disease (eg, heart, brain, and kidneys). Few questions exist as to which patients
      should be treated, although some controversy may still exist among authorities as
      to the selection of specific classes of antihypertensive therapy. Thus, it is now
      clear that no matter whether systolic or diastolic pressures are elevated (ie,
      greater than 139 mm Hg or 89 mm Hg, respectively), control of elevated pressure
      is indicated. One possible and provisional exception to this sweeping statement
      may relate to patients with borderline isolated systolic hypertension (between
      140 and 159 mm Hg, with diastolic pressures less than 90 mm Hg). This discussion
      concerns the treatment options that are presently available and offers guidelines
      as to which patients with hypertension may be more suitable for the various
      classes of agents that are available.

PMID- 11445064
TI  - Dyslipidemia.
AB  - The major goal in treatment of patients with dyslipidemia is to decrease the
      short- and long-term incidence of cardiovascular events, including myocardial
      infarction, unstable angina, stroke, and death. A second goal in patients with
      severe hypertriglyceridemia is to decrease the risk of acute pancreatitis.
      Improvement of the lipid profile can be achieved through a combination of
      aggressive lifestyle modification and effective drug therapy. Treatment should be
      tailored to the individual patient, based on the specific lipid abnormalities,
      the presence or absence of pre-existing coronary artery or other atherosclerotic
      vascular disease, and an assessment of overall cardiovascular risk.

PMID- 11445065
TI  - Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a
      possible factor in Parkinson's disease.
AB  - Parkinson's disease involves intracellular deposits of alpha-synuclein in the
      form of Lewy bodies and Lewy neurites. The etiology of the disease is unknown,
      however, several epidemiological studies have implicated environmental factors,
      especially pesticides. Here we show that several pesticides, including rotenone,
      dieldrin and paraquat, induce a conformational change in alpha-synuclein and
      significantly accelerate the rate of formation of alpha-synuclein fibrils in
      vitro. We propose that the relatively hydrophobic pesticides preferentially bind
      to a partially folded intermediate conformation of alpha-synuclein, accounting
      for the observed conformational changes, and leading to association and
      subsequent fibrillation. These observations suggest one possible underlying
      molecular basis for Parkinson's disease.

PMID- 11445066
TI  - Disulfide bonds stabilize JC virus capsid-like structure by protecting calcium
      ions from chelation.
AB  - To investigate the role of disulfide bonds in the capsid structure, a recombinant
      JC virus-like particle (VLP) was used. The major capsid protein, VP1, of the JC
      virus was expressed in yeast cells. The yeast-expressed VP1 was self-assembled
      into a VLP. Disulfide bonds were found in the VLP which caused dimeric and
      trimeric VP1 linkages as demonstrated by non-reducing SDS-PAGE. The VLP remained
      intact when disulfide bonds were reduced by dithiothreitol. The VLP without
      disulfide bonds could be disassembled into capsomeres by EGTA alone, but those
      with disulfide bonds could not be disassembled by EGTA. Capsomeres were
      reassembled into VLPs in the presence of calcium ions. Capsomeres formed
      irregular aggregations instead of VLPs when treated with diamide to reconstitute
      the disulfide bonds. These results indicate that disulfide bonds play an
      important role in maintaining the integrity of the JC VLP by protecting calcium
      ions from chelation.

PMID- 11445067
TI  - Caspases are reversibly inactivated by hydrogen peroxide.
AB  - Hydrogen peroxide (H2O2) is known to both induce and inhibit apoptosis, however
      the mechanisms are unclear. We found that H2O2 inhibited the activity of
      recombinant caspase-3 and caspase-8, half-inhibition occurring at about 17 microM
      H2O2. This inhibition was both prevented and reversed by dithiothreitol while
      glutathione had little protective effect. 100-200 microM H2O2 added to
      macrophages after induction of caspase activation by nitric oxide or serum
      withdrawal substantially inhibited caspase activity. Activation of H2O2-producing
      NADPH oxidase in macrophages also caused catalase-sensitive inactivation of
      cellular caspases. The data suggest that the activity of caspases in cells can be
      directly but reversibly inhibited by H2O2.

PMID- 11445068
TI  - Insulin modulates leptin-induced STAT3 activation in rat hypothalamus.
AB  - Insulin and leptin have overlapping effects in the control of energy homeostasis,
      but the molecular basis of this synergism is unknown. Insulin signals through a
      receptor tyrosine kinase that phosphorylates and activates the docking proteins
      IRSs (insulin receptor substrates), whereas the leptin receptor and its
      associated protein tyrosine kinase JAK2 (Janus kinase 2) mediate phosphorylation
      and activation of the transcription factor STAT3 (signal transducer and activator
      of transcription). Here, we present evidence for the integration of leptin and
      insulin signals in the hypothalamus. Insulin induced JAK2 tyrosine
      phosphorylation, leptin receptor phosphorylation which, in the presence of
      leptin, augmented the interaction between STAT3 and this receptor. Insulin also
      increased the leptin-induced phosphorylation of STAT3 and its activation. These
      results indicate that insulin modulates the leptin signal transduction pathway,
      and may provide a molecular basis for the coordinated effects of insulin and
      leptin in feeding behavior and weight control.

PMID- 11445069
TI  - Astaxanthin accumulation in Haematococcus requires a cytochrome P450 hydroxylase
      and an active synthesis of fatty acids.
AB  - Astaxanthin accumulation by green microalgae is a natural phenomenon known as red
      snows and blood rains. The fact that astaxanthin synthesis requires oxygen, NADPH
      and Fe(2+) led Cunningham and Gantt [Annu. Rev. Plant Physiol. Plant Mol. Biol.
      49 (1998) 557-583] to propose that a cytochrome P450-dependent enzyme might be
      involved in the transformation of beta-carotene to astaxanthin. In Haematococcus
      only esterified astaxanthin molecules accumulate, but it is not determined
      whether a fatty acid synthesis should occur simultaneously to allow pigment
      accumulation. The aim of this contribution was to answer these two questions
      using specific inhibitors of beta-carotene (norflurazon) and fatty acid
      (cerulenin) synthesis, and of cytochrome P450 enzyme activity (ellipticine).

PMID- 11445070
TI  - A dual-specific Glu-tRNA(Gln) and Asp-tRNA(Asn) amidotransferase is involved in
      decoding glutamine and asparagine codons in Acidithiobacillus ferrooxidans.
AB  - The gatC, gatA and gatB genes encoding the three subunits of glutamyl-tRNA(Gln)
      amidotransferase from Acidithiobacillus ferrooxidans, an acidophilic bacterium
      used in bioleaching of minerals, have been cloned and expressed in Escherichia
      coli. As in Bacillus subtilis the three gat genes are organized in an operon-like
      structure in A. ferrooxidans. The heterologously overexpressed enzyme converts
      Glu-tRNA(Gln) to Gln-tRNA(Gln) and Asp-tRNA(Asn) to Asn-tRNA(Asn). Biochemical
      analysis revealed that neither glutaminyl-tRNA synthetase nor asparaginyl-tRNA
      synthetase is present in A. ferrooxidans, but that glutamyl-tRNA synthetase and
      aspartyl-tRNA synthetase enzymes are present in the organism. These data suggest
      that the transamidation pathway is responsible for the formation of Gln-tRNA and
      Asn-tRNA in A. ferrooxidans.

PMID- 11445071
TI  - One-electron reduction potentials of dietary carotenoid radical cations in
      aqueous micellar environments.
AB  - The one-electron reduction potentials of the radical cations of five dietary
      carotenoids (beta-carotene, canthaxanthin, zeaxanthin, astaxanthin and lycopene)
      in aqueous micellar environments have been obtained from a pulse radiolysis study
      of electron transfer between the carotenoids and tryptophan radical cations as a
      function of pH, and lie in the range of 980-1060 mV. These values are consistent
      with our observation that the carotenoid radical cations oxidise tyrosine and
      cysteine. The decays of the carotenoid radical cations in the absence of added
      reactants suggest a distribution of exponential lifetimes. The radicals persist
      for up to about 1 s, depending on the medium.

PMID- 11445072
TI  - Complex formation and submembranous localization of annexin 2 and S100A10 in live
      HepG2 cells.
AB  - The Ca(2+) and membrane binding protein annexin 2 can form a heterotetrameric
      complex with the S100A10 protein and this complex is thought to serve a bridging
      or scaffolding function in the membrane underlying cytoskeleton. To elucidate
      which of the subunits targets the complex to the subplasmalemmal region in live
      cells we employed YFP/CFP fusion proteins and live cell imaging in HepG2 cells.
      We show that monomeric annexin 2 is targeted to the plasma membrane whereas non
      complexed S100A10 acquires a general cytosolic distribution. Co-expression of
      S100A10 together with annexin 2 and the resulting complex formation, however,
      lead to a recruitment of S100A10 to the plasma membrane thus identifying annexin
      2 as the membrane targeting subunit.

PMID- 11445073
TI  - A novel approach for purification of recombinant proteins using the dextran
      binding domain.
AB  - Using the dextran-binding domain (DBD) of a type of glucosyltransferase (GTF)
      from Streptococcus sobrinus, we have developed a novel method for purifying
      recombinant proteins. DBD-tagged green and red fluorescent proteins as well as
      the parent GTF and DBD moiety were adsorbed well to commercially available cross
      linked dextran (such as Sephadex beads and Sephacryl beads), and eluted
      efficiently with water-soluble dextran. The purity of the eluted proteins after
      this one-step affinity purification was approximately 90% or better. The results
      suggest that DBD can be used as a powerful carrier for purification of various
      recombinant proteins.

PMID- 11445074
TI  - The specificity of lysosomal tripeptidyl peptidase-I determined by its action on
      angiotensin-II analogues.
AB  - Tripeptidyl peptidase-I (TPP-I) is a lysosomal peptidase which cleaves
      tripeptides from the N-terminus of peptides. The function of the enzyme is
      unclear but its importance is demonstrated by the fact that mutations in TPP-I
      are responsible for late infantile neuronal ceroid lipofuscinosis, a lethal
      lysosomal storage disease. As a step towards identifying its natural substrates,
      we have used a series of synthetic peptides, based on angiotensin-II, to explore
      the effects of peptide chain length and the effects of amino acid substitutions
      at the P1 and P1' positions on the rate of catalysis. With the exception of
      angiotensin-(1-8) (angiotensin-II), which is a relatively poor substrate for TPP
      I, the rate of catalysis increases with increasing chain length. K(cat)/K(m)
      values increase 50-fold between angiotensin-(1-5) and angiotensin-(1-14). TPP-I
      shows little specificity for the nature of the amino acids in the P1 and P1'
      positions, K(cat)/K(m) values varying only 5-fold for a range of substitutions.
      However, Pro or Lys in the P1 position and Pro in the P1' positions are
      incompatible with TPP-I activity. These observations suggest that TPP-I is a non
      specific, but essential, peptidase involved in the latter stages of lysosomal
      protein degradation.

PMID- 11445075
TI  - Exploring the active site of yeast xylose reductase by site-directed mutagenesis
      of sequence motifs characteristic of two dehydrogenase/reductase family types.
AB  - Starting from a common tyrosine, yeast xylose reductases (XRs) contain two
      conserved sequence motifs corresponding to the catalytic signatures of single
      domain reductases/epimerases/dehydrogenases (Tyr(n)-(X)3-Lys(n+4)) and aldo/keto
      reductases (AKRs) (Tyr(n)-(X)28-Lys(n+29)). Tyr(51), Lys(55) and Lys(80) of XR
      from Candida tenuis were replaced by site-directed mutagenesis. The purified
      Tyr(51)--> Phe and Lys(80)-->Ala mutants showed turnover numbers and catalytic
      efficiencies for NADH-dependent reduction of D-xylose between 2500- and 5000-fold
      below wild-type levels, suggesting a catalytic role of both residues. Replacing
      Lys(55) by Asn, a substitution found in other AKRs, did not detectably affect
      binding of coenzymes, and enzymatic catalysis to carbonyl/alcohol
      interconversion. The contribution of Tyr(51) to rate enhancement of aldehyde
      reduction conforms with expectations for the general acid catalyst of the
      enzymatic reaction.

PMID- 11445076
TI  - Properties of the Escherichia coli rhodanese-like protein SseA: contribution of
      the active-site residue Ser240 to sulfur donor recognition.
AB  - The product of Escherichia coli sseA gene (SseA) was the subject of the present
      investigation aimed to provide a tool for functional classification of the
      bacterial proteins of the rhodanese family. E. coli SseA contains the motif
      CGSGVTA around the catalytic cysteine (Cys238). In eukaryotic sulfurtransferases
      this motif discriminates for 3-mercaptopyruvate:cyanide sulfurtransferase over
      thiosulfate:cyanide sulfurtransferases (rhodanese). The biochemical
      characterization of E. coli SseA allowed the identification of the first
      prokaryotic protein with a preference for 3-mercaptopyruvate as donor substrate.
      Replacement of Ser240 with Ala showed that the presence of a hydrophobic residue
      did not affect the binding of 3-mercaptopyruvate, but strongly prevented
      thiosulfate binding. On the contrary, substitution of Ser240 with an ionizable
      residue (Lys) increased the affinity for thiosulfate.

PMID- 11445077
TI  - Accumulation of cardiolipin and lysocardiolipin in fibroblasts from Tangier
      disease subjects.
AB  - Tangier disease (TD) is an inherited disorder of lipid metabolism characterized
      by very low high density lipoprotein (HDL) plasma levels, cellular cholesteryl
      ester accumulation and reduced cholesterol excretion in response to HDL
      apolipoproteins. Molecular defects in the ATP binding cassette transporter 1
      (ABCA1) have recently been identified as the cause of TD. ABCA1 plays a key role
      in the translocation of cholesterol across the plasma membrane, and defective
      ABCA1 causes cholesterol storage in TD cells. Not only cholesterol efflux, but
      also phospholipid efflux was shown to be impaired in TD cells. By use of thin
      layer chromatography, high performance liquid chromatography and time-of-flight
      secondary ion mass spectrometry, we characterized the cellular phospholipid
      content in fibroblasts from three homozygous TD patients. The cellular content of
      the major phospholipids was not found to be significantly altered in TD
      fibroblasts. However, the two phospholipids cardiolipin and lysocardiolipin,
      which make up minute amounts in normal cells, were at least 3-5-fold enriched in
      fibroblasts from TD subjects. A structurally closely related phospholipid
      (lysobisphosphatidic acid) has recently been shown to be enriched in Niemann-Pick
      type C, another lipid storage disorder. Altogether these data may indicate that
      the role of these phospholipids is a regulatory one rather than that of a bulk
      mediator of cholesterol solubilization in sterol trafficking and efflux.

PMID- 11445078
TI  - An activating mutation in the gamma1 subunit of the AMP-activated protein kinase.
AB  - The AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a
      catalytic alpha subunit and two regulatory subunits, beta and gamma. The gamma
      subunit is essential for enzyme activity by virtue of its binding to the C
      terminus of the alpha subunit and appears to play some role in the determination
      of AMP sensitivity. We demonstrate that a gamma1R70Q mutation causes a marked
      increase in AMPK activity and renders it largely AMP-independent. This activation
      is associated with increased phosphorylation of the alpha subunit activation loop
      T172. These in vitro characteristics of AMPK are also reflected in increased
      intracellular phosphorylation of one of its major substrates, acetyl-CoA
      carboxylase. These data illustrate the importance of the gamma1 subunit in the
      regulation of AMPK and its modulation by AMP.

PMID- 11445079
TI  - Transcriptome meets metabolome: hierarchical and metabolic regulation of the
      glycolytic pathway.
AB  - The fact that information flows from DNA to RNA to protein to function suggests
      that regulation is 'hierarchical', i.e. dominated by regulation of gene
      expression. In the case of dominant regulation at the metabolic level, however,
      there is no quantitative relationship between mRNA levels and function. We here
      develop a method to quantitate the relative contributions of metabolic and
      hierarchical regulation. Applying this method to the glycolytic flux in three
      species of parasitic protists, we conclude that it is rarely regulated by gene
      expression alone. This casts strong doubts on whether transcriptome and proteome
      analysis suffices to assess biological function.

PMID- 11445080
TI  - Electrogenic reduction of the primary electron donor P700 by plastocyanin in
      photosystem I complexes.
AB  - An electrometric technique was used to investigate electron transfer between
      spinach plastocyanin (Pc) and photooxidized primary electron donor P700 in
      photosystem I (PS I) complexes from the cyanobacterium Synechocystis sp. PCC
      6803. In the presence of Pc, the fast unresolvable kinetic phase of membrane
      potential generation related to electron transfer between P700 and the terminal
      iron-sulfur acceptor F(B) was followed by additional electrogenic phases in the
      microsecond and millisecond time scales, which contribute approximately 20% to
      the overall electrogenicity. These phases are attributed to the vectorial
      electron transfer from Pc to the protein-embedded chlorophyll dimer P700(+)
      within the PsaA/PsaB heterodimer. The observed rate constant of the millisecond
      kinetic phase exhibited a saturation profile at increasing Pc concentration,
      suggesting the formation of a transient complex between Pc and PS I with the
      dissociation constant K(d) of about 80 microM. A small but detectable fast
      electrogenic phase was observed at high Pc concentration. The rate constant of
      this phase was independent of Pc concentration, indicating that it is related to
      a first-order process.

PMID- 11445081
TI  - AtBS14a and AtBS14b, two Bet1/Sft1-like SNAREs from Arabidopsis thaliana that
      complement mutations in the yeast SFT1 gene.
AB  - SNAREs are membrane-associated proteins that play a central role in vesicle
      targeting and intra-cellular membrane fusion reactions in eukaryotic cells. Here
      we describe the identification of AtBS14a and AtBS14b, putative SNAREs from
      Arabidopsis thaliana that share 60% amino acid sequence identity. Both AtBS14a
      and BS14b are dosage suppressors of the temperature-sensitive growth defect in
      sft1-1 cells and over-expression of either AtBS14a or AtBS14b can support the
      growth of sft1Delta cells but not bet1Delta cells. These data together with
      structure-function and biochemical studies presented herein suggest that AtBS14a
      and AtBS14b share properties that are consistent with them being members of the
      Bet1/Sft1 SNARE protein family.

PMID- 11445082
TI  - Refinement of the adPEO linked locus on Chr10 and analysis of MRS4 and three
      other candidate genes.

PMID- 11445083
TI  - Identification of bacterial homologues of the Ku DNA repair proteins.

PMID- 11445084
TI  - Echinoid bioerosion and herbivory on Kenyan coral reefs: the role of protection
      from fishing.
AB  - During feeding, echinoids remove a large proportion of calcium carbonate in
      addition to the algae growing on dead coral and are consequently of importance in
      estimating the turnover of organic and inorganic carbon in coral reefs. Rates of
      herbivory and the erosion of dead coral substratum, referred to as bioerosion, by
      the most abundant echinoid species in Kenyan reefs, Echinothrix diadema
      (Linnaeus), Diadema setosum (Leske), D. savignyi (Michelin) and Echinometra
      mathaei (de Blainville), were compared in three different reef categories with
      different histories of fishing and its exclusion. These were reefs: (i) protected
      within Marine National Parks, which exclude all forms of fishing, coral and shell
      collection for more than 25 years; (ii) one reef within a Marine Park, which has
      received protection from fishing activities for 8 years (referred to as 'newly
      protected' reef); and (iii) unprotected reefs, which experience heavy fishing and
      some coral collection. The aim was to investigate the grazing and bioerosion
      activity by the above echinoid species in these reef categories. We surveyed sea
      urchin population densities and determined their rates of bioerosion and
      herbivory per individual and square meter. Individual rates of bioerosion and
      herbivory, of the species D. setosum, D. savignyi and E. diadema were estimated
      from laboratory gut content analysis and gut evacuation experiments in the field,
      using elevated underwater cages. Individual rates of bioerosion and herbivory of
      E. mathaei were obtained from a previous field study [J. Exp. Mar. Biol. Ecol.
      147 (1991) 121]. Sea urchin bioerosion was greater than herbivory for all studied
      species and proportional to the body size of the sea urchin species. The large
      bodied E. diadema exhibited the highest bioerosion and herbivory rates (5.5+/-0.9
      and 2.2+/-0.3 g individual(-1) day(-1), respectively) followed by D. setosum
      (1.8+/-0.3 and 1.1+/-0.2 g individual(-1) day(-1)) and D. savignyi (0.7+/-0.2 and
      0.4+/-0.1 g individual(-1) day(-1)). Highest sea urchin densities were recorded
      at unprotected reefs (6.2+/-1.5 individual m(-2)), and therefore, bioerosion and
      herbivory by sea urchins were also highest in this reef category (1180+/-230 g
      CaCO(3) m(-2) year(-1) and 450+/-77 g algae m(-2) year(-1)). Protected reefs
      recorded 20 times lower sea urchin bioerosion and herbivory rates (50.3+/-25.8 g
      CaCO(3) m(-2) year(-1) and 20.7+/-10.4 g algae m(-2) year(-1)), due to the low
      sea urchin population densities in these reefs (0.06+/-0.01 individual m(-2)).
      The newly protected reef, with intermediate number of sea urchins (1.2+/-0.1
      individual m(-2)), had intermediate rates of sea urchin bioerosion and herbivory
      (711+/-157 g CaCO(3) m(-2) year(-1) and 299+/-63 g algae m(-2) year(-1)). These
      findings suggest that echinoids are important in the carbon cycle and reef
      development, and that fishing can influence these ecological processes.

PMID- 11445085
TI  - Comparison of age-length and growth-increment general growth models of the
      Schnute type in the Pacific Blue Mussel, Mytilus trossulus Gould.
AB  - Models of Mytilus growth, based mostly on length-at-age data, have typically
      taken the form exemplified by the von Bertalanffy or Gompertz formulations. These
      models require assumptions about the form of the growth curve. We used the
      Schnute general growth model to examine growth in the Pacific Blue Mussel,
      Mytilus trossulus, in Prince William Sound, AK. The Schnute model provides a
      convenient analytical method for selecting among all previously published growth
      models. Mussels were tagged with individually numbered tags at 13 sites in July
      1997 and were collected in July 1998. Age was determined from surface growth
      rings on the shell, and shell length at maximum annulus was measured. Annual
      deposition of the growth rings was verified through radial sections of mussel
      valves, aided by acetate peels, in conjunction with in situ annual growth
      measurements. Growth was modeled with the Schnute general growth model for age
      length data or with an analog of the Schnute model for growth-increment data.
      Bootstrap confidence intervals were obtained for all parameters of the model and
      for model predicted lengths at each annulus. Confidence intervals of the between
      annuli growth-increment model overlapped those of the age-length model at all
      annuli when growth over the entire range of ages in the population was estimated.
      Differences in growth model parameters between the age-length model and the mark
      recapture analog could be accounted for solely by inherent differences in age
      based versus length-based models. Growth estimates generated from between-annuli
      measurements were equivalent to growth estimates obtained from mark-recapture
      measurements of annual growth. In general, mussel growth at our sites was best
      described by the von Bertalanffy submodel.

PMID- 11445086
TI  - Cell cycle regulation in a dinoflagellate, Amphidinium operculatum:
      identification of the diel entraining cue and a possible role for cyclic AMP.
AB  - This research describes the diel phasing of the cell cycle in the dinoflagellate,
      Amphidinium operculatum Claparede and Lachmann, and investigates the mechanisms
      that serve to link the cell cycle to the diel cycle. Unlike many dinoflagellates,
      A. operculatum has a naturally high division rate of approximately 1 division
      day(-1), which yields a nearly synchronous population, making it useful for
      population studies. When grown on a 16:8 h light/dark cycle, S-phase begins 10 h
      and mitosis 14-16 h after the onset of light, as determined by flow cytometry.
      Alterations in the timing of the dark/light and light/dark transitions showed
      that the cell cycle is entrained by the dark/light transition, with the
      light/dark cue being uninvolved. Cells in logarithmic phase growth also undergo
      diel changes in cell size (9-14 &mgr;m), reaching a maximum size late in the
      light phase, concurrent with mitosis. Stationary phase cells or cells blocked in
      G1 of the cell cycle with a cell cycle inhibitor, olomoucine, showed no size
      changes or reduced size changes over the diel cycle, suggesting a coupling of
      cell size to the cell division cycle. In Euglena, cAMP-dependent signaling
      appears to mediate diel phasing of the cell cycle. Therefore, the role of cAMP in
      cell cycle control in A. operculatum was investigated. Measurement of
      intracellular cAMP by radioimmunoassay (RIA) revealed that cAMP concentrations
      varied on a diel basis, but increases observed appeared to correlate with cell
      size increases, and did not correlate with light cues at the dark/light or
      light/dark transition. However, when cells were treated with the cAMP
      phosphodiesterase inhibitor, IBMX, cell cycle progression was inhibited at both
      the G1/S and the G2/M phase transitions. This supports a role for cAMP-dependent
      signaling in the dinoflagellate cell cycle and is in agreement with the
      documented role of cAMP in the cell cycle control of higher eukaryotes.

PMID- 11445087
TI  - Laboratory investigations of the effects of predator sex and size on prey
      selection by the Asian crab, Hemigrapsus sanguineus.
AB  - Laboratory studies have shown that the nonindigenous Asian shore crab,
      Hemigrapsus sanguineus, readily consumes three species of commercial bivalves:
      blue mussels, Mytilus edulis, soft-shell clams, Mya arenaria, and oysters,
      Crassostrea virginica. Although crabs can eat bivalves of a wide size range, they
      preferred the smaller prey (</=10 mm SL). Prey critical size limits exist for M.
      edulis and C. virginica, but not M. arenaria, possibly because of differences in
      shell characteristics among the three species. Crabs preferred M. arenaria over
      both M. edulis and C. virginica, and M. edulis was strongly preferred over C.
      virginica in pairwise comparison tests. Experiments to determine feeding rates on
      mussels showed that H. sanguineus can consume large numbers of mussels daily
      (12.7+/-11.6 mussels day(-1); sexes pooled; N=59). Mussel consumption rates
      increased with size of the predator and male crabs consumed more mussels than did
      similarly sized female crabs. The high densities of Hemigrapsus that occur in the
      wild, their effectiveness as predators of juvenile bivalves and their large
      appetites suggest an important role for these predators in restructuring the prey
      communities in habitats into which they have been introduced.

PMID- 11445088
TI  - Ichthyotoxicity studies of milkfish Chanos chanos fingerlings exposed to a
      harmful dinoflagellate Alexandrium minutum.
AB  - Milkfish (Chanos chanos Forsskal) fingerlings were treated with toxic, nontoxic
      dinoflagellate Alexandrium minutum cells or toxic algal extract in the water
      medium without any aeration. Mortality of fish increased with increasing
      concentrations of toxic, nontoxic algal cells and water-soluble toxic algae
      extract. Milkfish fingerlings, which were exposed to toxic algae (1.5x10(4)
      3.0x10(4) cells/ml) or algal extract [5.13x10(3)-2.05x10(4) cells/ml, 0.195
      MU/10(4) cells (toxin concentration)] for 24 h, revealed by light microscopic
      observations a noticeable edema, hyperplasia and necrosis of secondary gill
      lamellae. The same toxicological symptom was observed in fish exposed to pure
      saxitoxin (STX) (6.475x10(-2) &mgr;g/ml) in the water medium. A higher critical
      oxygen pressure and oxygen consumption rate were also found in the milkfish
      fingerlings exposed to toxic algae extract (5.13x10(3)-2.05x10(4) cells/ml) and
      STX (6.475x10(-2) &mgr;g/ml). The cells of nontoxic A. minutum did not cause the
      gill damage to milkfish, and the extract of nontoxic algae did not cause an
      increase in oxygen consumption rate or critical oxygen demand of milkfish. From
      these results, we infer that toxic cells and its extract cause nonspecific
      response in gill tissues of milkfish. An instant increase in oxygen consumption
      rate and oxygen demand may be one of the major causes of fish death.

PMID- 11445089
TI  - The importance of rock crab (Cancer irroratus) for growth, condition and ovary
      development of adult American lobster (Homarus americanus).
AB  - The rock crab (Cancer irroratus) fishery is a growing industry in eastern Canada.
      Considering that American lobster (Homarus americanus) is highly dependent on the
      rock crab as a food source, questions have arisen as to the impacts such a
      fishery would have. This study examines how different rations of rock crab can
      affect somatic growth, condition and ovary development of mature lobster,
      following molt. We tested the effect of four diets containing various amounts of
      rock crab, blue mussel and green sea urchin. The four diets were: a reference
      diet where 80% of the energy was provided by rock crab (T), a diet with half the
      crab content of the reference diet but containing as much protein (isoproteinic)
      as the reference diet (E1), a diet without crab but isoproteinic with the
      reference diet (E2), and a diet without crab but with as much energy (isocaloric)
      as the reference diet (E3). In general, lobsters fed a diet without rock crab
      showed lower glycogen and lipid content and higher water content in the digestive
      gland. Growth of chela muscles was lower, although diet did not have any effect
      on protein concentration. Ovary development was stunted in females. Differences
      were mostly striking in diet E3, which contained less proteins than the reference
      diet. Results obtained from diet E2 were also significantly different from the
      reference diet and not from E3, suggesting that mussel and urchin, even if given
      in a greater amount, are not equivalent to crab and cannot fully compensate the
      absence of this essential component of the lobster's diet. The importance of rock
      crab for lobster may be due to its high protein content and presence of
      particular amino acids. Our results strongly suggest that the development and
      management of a rock crab fishery should be cautious and governed by a multi
      species approach.

PMID- 11445090
TI  - Ionic regulation in aglomerular tropical estuarine pufferfishes submitted to sea
      water dilution.
AB  - Two common tropical estuarine pufferfishes were used in this study. The main
      species was Sphoeroides testudineus Linnaeus, 1758, a very abundant species in
      the estuaries of Paranagua Bay (Parana, Brazil), found in waters of salinity
      between 0 per thousand (tidal creeks) and 34 per thousand (tidal plains). The
      second species was S. greeleyi Gilbert, 1900, a species limited in distribution
      to an area of higher salinity ( approximately 30 per thousand) than S.
      testudineus. The present work thus aimed at evaluating the capacity of ionic
      regulation of both species of pufferfishes when submitted to salinity decrease,
      relating the results with both species' distribution in nature. Ion regulation
      curves for sodium (Na(+)), chloride (Cl(-)), and magnesium (Mg(2+)) ions after 6
      h and 15 days of exposure of the abundant S. testudineus to the salinities of 30
      per thousand, 20 per thousand, 10 per thousand, and 5 per thousand were
      elaborated, as well as for Cl(-) and Mg(2+) after 6 h and 15 days of exposure of
      both species to the extreme salinities of 35 per thousand and 5 per thousand.
      Both species kept their plasma Cl(-) ( approximately 120-160 mM), and Mg(2+) (
      approximately 1.3 mM) concentrations stable, as did S. testudineus for Na(+) (
      approximately 130 mM). Na(+) (measured only for S. testudineus) and Cl(-) were
      either hyper-regulated (in 5 per thousand) or kept iso-ionic ( approximately 7-10
      per thousand), but more often hypo-regulated (20-35 per thousand). In contrast,
      Mg(2+) was strongly hypo-regulated in all salinities. According to their
      distribution records in nature, S. greeleyi was less able to tolerate strong sea
      water dilution, showing mortality after 5 days in 5 per thousand water. These
      estuarine pufferfishes are thus efficient regulators of plasma ionic
      concentrations in diluted sea water, as expected from their occupation of
      estuaries. The experiments have supported the distribution records of both
      species in the estuarine complex and resident estuarine species were thus
      characterized with respect to their osmoregulatory capacities.

PMID- 11445091
TI  - Improving the safety of patients during clinical research.

PMID- 11445092
TI  - Place of intracytoplasmic sperm injection in management of male infertility.

PMID- 11445093
TI  - EDRF transcripts and diagnosis of variant Creutzfeldt-Jakob disease.

PMID- 11445094
TI  - Bacterial pneumonia: commoner than perceived.

PMID- 11445095
TI  - Towards improving prehospital trauma care.

PMID- 11445096
TI  - Prevention of overwhelming sepsis in asplenic patients: could do better.

PMID- 11445097
TI  - AIDS: unbeatable 20 years on.

PMID- 11445098
TI  - Responding to the changing face of paediatric cardiology.

PMID- 11445099
TI  - Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for
      the treatment of non-male-factor infertility: a randomised controlled trial.
AB  - BACKGROUND: Intracytoplasmic sperm injection (ICSI) is a more invasive option
      than conventional in-vitro fertilisation (IVF), which can be successful even when
      semen characteristics are poor. Reports of higher fertilisation rates after ICSI
      suggest that this technique may be better than the conventional method for all
      couples seeking IVF. We undertook a multicentre randomised controlled trial
      comparing clinical outcome after ICSI or traditional IVF in couples with non-male
      factor infertility. METHODS: 415 eligible and consenting couples at four UK
      centres were randomly assigned IVF or ICSI (total 435 treatment cycles: IVF 224;
      ICSI 211). Usual clinical and laboratory protocols for the two treatment
      procedures were followed in each of four participating centres. The primary
      outcome was the implantation rate (number of gestation sacs per embryo replaced
      expressed as a percentage). Secondary outcomes were pregnancy and fertilisation
      rates associated with each treatment. Analyses were by intention to treat.
      FINDINGS: The implantation rate was higher in the IVF group than in the ICSI
      group (95/318 [30%] vs 72/325 [22%]; relative risk 1.35 [95% CI 1.04-1.76]). The
      pregnancy rate per cycle was also higher after IVF (72 [33%] vs 53 [26%]; 1.17
      [0.97-1.35]). Mean associated laboratory time was significantly shorter with IVF
      than with ICSI (22.9 [SD 12.1] vs 74.0 [38.1] min; 95% CI for difference 45.6
      56.6). INTERPRETATION: ICSI offers no advantage over IVF in terms of clinical
      outcome in cases of non-male-factor infertility. Our results support the current
      practice of reserving ICSI only for severe male-factor problems.

PMID- 11445100
TI  - Outcome in the second year of life after in-vitro fertilisation by
      intracytoplasmic sperm injection: a UK case-control study.
AB  - BACKGROUND: There have been reports suggesting that children born after in-vitro
      fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of
      neurodevelopmental delay. We have undertaken a case-control study of this issue.
      METHODS: We studied 208 singleton children conceived by ICSI and a control group
      of 221 normally conceived singleton children. Children were recruited from 22
      fertility centres and local nurseries throughout the UK. Controls were selected
      to match cases as closely as possible for social class, maternal educational
      attainment, region, sex, and race. The primary outcome measure was
      neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal
      health, and congenital abnormalities. A single examiner assessed all the
      children. FINDINGS: A follow-up rate of 90% for the ICSI group was achieved at a
      mean age of 17 months. No difference between the study children and controls was
      found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any
      subscales on the Griffiths' scales of mental development. Perinatal outcome was
      similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%],
      p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in
      the study group. Rates of major congenital abnormality were also similar overall
      (ten [4.8%] study vs ten [4.5%] control), although there were significantly more
      congenital anomalies among children born to fathers with oligozoospermia than in
      other children. INTERPRETATION: This population study did not show any
      significant difference between children conceived after ICSI and their naturally
      conceived peers in terms of physical health and development.

PMID- 11445102
TI  - Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on
      neointima proliferation after coronary stent placement (ISAR-3): a randomised,
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: Vascular infection with Chlamydia pneumoniae might boost inflammatory
      responses that play a pivotal part in neointima formation, which is the main
      cause of restenosis after stenting. Our aim was to investigate whether or not
      treatment of C pneumoniae infection with antibiotics prevents restenosis after
      coronary stent placement. METHODS: We enrolled 1010 consecutive patients with
      successful coronary stenting into a randomised, double-blind trial. Patients
      received the macrolide antibiotic roxithromycin 300 mg once daily for 28 days
      (506), or placebo (504). Primary endpoint was frequency of restenosis (diameter
      stenosis >50%) at follow-up angiography, and secondary endpoint was rate of
      target vessel revascularisation during the year after stenting. A prespecified
      secondary analysis addressed treatment effect with respect to titre of C
      pneumoniae in serum. Analysis was by intention to treat. FINDINGS: Rate of
      angiographic restenosis was 31% (157 lesions) in the roxithromycin group and 29%
      (148) in the placebo group (relative risk 1.08 [95% CI 0.92-1.26]; p50.43),
      corresponding to a rate of target vessel revascularisation of 19% (120) and 17%
      (105), respectively (1.13 [0.95-1.36]; p50.30). The combined 1-year rates of
      death and myocardial infarction were 7% (36) in the roxithromycin group and 6%
      (30) in the placebo group (p50.45). We showed a significant interaction between
      treatment and C pneumoniae antibody titre (p50.038 for restenosis, p50.006 for
      revascularisation), favouring roxithromycin at high titres (adjusted odds ratios
      at a titre of 1/512 were 0.44 [0.19-1.06] and 0.32 [0.13-0.81], respectively).
      INTERPRETATION: Non-selective use of roxithromycin is inadequate for prevention
      of restenosis after coronary stenting. There is, however, a differential effect
      dependent on C pneumoniae titres. In patients with high titres, roxithromycin
      reduced the rate of restenosis.

PMID- 11445103
TI  - Enteral human IgG for prevention of necrotising enterocolitis: a placebo
      controlled, randomised trial.
AB  - BACKGROUND: Neonatal necrotising enterocolitis is a serious, commonly fatal
      disease in premature neonates. Although feeding with expressed breast milk and
      other good nursery practices are partly protective, preventive measures are
      needed. Treating neonates enterally with a mixture of human IgA and IgG, prepared
      from donated blood, has been claimed to protect against necrotising
      enterocolitis. However, no IgA preparation is available in Australia. Our aim,
      therefore, was to identify whether or not enteral IgG could prevent the disorder.
      METHODS: We did a multicentre, double-blind, placebo- controlled trial. We
      randomly assigned 768 infants to receive human IgG 1200 mg/kg daily, and 761 to
      receive placebo, for up to 28 days. Treatment began at the same time as enteral
      feeding. The primary outcome measure was the proportion of infants who developed
      definite necrotising enterocolitis during the trial, and any deaths that resulted
      from the disorder in the treatment and placebo groups. Analysis was on an
      intention-to-treat basis. FINDINGS: 43 infants developed definite necrotising
      enterocolitis in the IgG group, ten of whom died. In the placebo group, 41
      infants contracted the disorder and six died (p=0.47). 25 infants on IgG and 36
      on placebo had suspect necrotising enterocolitis (p=0.14). INTERPRETATION:
      Supplementation of enteral feeds with human IgG does not reduce necrotising
      enterocolitis.

PMID- 11445104
TI  - A three-item scale for the early prediction of stroke recovery.
AB  - BACKGROUND: Accurate assessment of prognosis in the first hours of stroke is
      desirable for best patient management. We aimed to assess whether the extent of
      ischaemic brain injury on magnetic reasonance diffusion-weighted imaging (MR DWI)
      could provide additional prognostic information to clinical factors. METHODS: In
      a three-phase study we studied 66 patients from a North American teaching
      hospital who had: MR DWI within 36 h of stroke onset; the National Institutes of
      Health Stroke Scale (NIHSS) score measured at the time of scanning; and the
      Barthel Index measured no later than 3 months after stroke. We used logistic
      regression to derive a predictive model for good recovery. This logistic
      regression model was applied to an independent series of 63 patients from an
      Australian teaching hospital, and we then developed a three-item scale for the
      early prediction of stroke recovery. FINDINGS: Combined measurements of the NIHSS
      score (p=0.01), time in hours from stroke onset to MR DWI (p=0.02), and the
      volume of ischaemic brain tissue on MR DWI (p=0.04) gave the best prediction of
      stroke recovery. The model was externally validated on the Australian sample with
      0.77 sensitivity and 0.88 specificity. Three likelihood levels for stroke
      recovery-low (0-2), medium (3-4), and high (5-7)-were identified on the three
      item scale. INTERPRETATION: The combination of clinical and MR DWI factors
      provided better prediction of stroke recovery than any factor alone, shortly
      after admission to hospital. This information was incorporated into a three-item
      scale for clinical use.

PMID- 11445105
TI  - Alarming asystole.

PMID- 11445106
TI  - Molecular diagnosis of visceral herpes zoster.
AB  - Patients with disseminated herpes zoster may present with severe abdominal pain
      that results from visceral involvement of varicella-zoster-virus infection. In
      the absence of cutaneous eruptions of herpes zoster, visceral herpes zoster is
      extremely difficult to diagnose. This diagnostic difficulty has the potential to
      cause devastating delays in treatment. We report a case series of four patients
      with visceral herpes zoster in whom large concentrations of DNA from varicella
      zoster virus were detectable in blood by PCR before signs of infection appeared
      on the skin, thus enabling early diagnosis and treatment.

PMID- 11445107
TI  - Degradation of albumin in meningococcal sepsis.
AB  - We postulate that the proteolytic degradation of albumin into fragments could
      link the rapidity of the shock, rash, and hypocalcaemia associated with
      meningococcal sepsis. We examined urine of children with meningococcal disease
      and urine from control children with no sepsis and found albumin fragments of
      about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with
      meningococcal sepsis and associated purpura. Exogenous or endogenous proteases,
      or both, may be released in severe meningococcal sepsis and, in association with
      an inadequate antiprotease response, result in albumin degradation. This may be a
      contributory factor to the rapid shock, hypocalcaemia, and rash seen in
      meningococcal sepsis.

PMID- 11445108
TI  - Risk of trisomy 21 in offspring of patients with Klinefelter's syndrome.
AB  - Intracytoplasmic sperm injection (ICSI) has given some patients with
      Klinefelter's syndrome (ie, men with an XXY sex-chromosome profile) the chance to
      become fathers, but the genetic makeup of the spermatozoa used for the injection
      is a concern. We studied the segregation of the sex chromosomes and chromosomes 1
      and 21 by multicolour fluorescence in-situ hybridisation in a patient with non
      mosaic Klinefelter's syndrome who was a candidate for ICSI. As other workers have
      found, we saw a higher rate of 24,XX and 24,XY spermatozoa in the patient than in
      controls. However, we also found a much higher frequency of disomy 21 in the
      spermatozoa of this patient than in controls (6.2 vs 0.4%). Any child conceived
      by ICSI using this man's sperm will thus have a proportionally higher risk of
      trisomy 21.

PMID- 11445109
TI  - Arthropod dermatoses acquired in the UK and overseas.
AB  - International tourism to tropical and sub-tropical areas, both to resource-poor
      and developed countries, has almost trebled within the past 20 years. We examined
      the records of patients referred to the Liverpool School of Tropical Medicine
      over 6 years. 46 (63%) of infestations originated in the UK. Ticks were most
      common in the UK (19 cases, 41%) whereas myiasis was most common in travellers
      (18 cases, 67%). These records suggest that whereas many overseas acquired
      infestations are potentially dangerous if infections are transmitted, ticks
      constitute the greatest risk, and both domestic and exotic species may act as
      disease vectors.

PMID- 11445110
TI  - Annan calls for action on AIDS at UN meeting.

PMID- 11445113
TI  - Brain plasticity allows recognition of transplanted hands.

PMID- 11445114
TI  - Breast self examination does more harm than good, says task force.

PMID- 11445115
TI  - Potential specific breast cancer treatment uncovered in mouse experiments.

PMID- 11445116
TI  - New perspectives on the management of intersex.

PMID- 11445117
TI  - Alleged biotech espionage rocks Japan.

PMID- 11445119
TI  - USA and Brazil end dispute over essential drugs.

PMID- 11445120
TI  - Israeli Parliament set to debate euthanasia bill.

PMID- 11445121
TI  - Ireland tackles antimicrobial resistance in hospitals.

PMID- 11445122
TI  - United Nations agency launches new appeal for Palestinian refugees.

PMID- 11445123
TI  - Healthy volunteer dies in US physiology study.

PMID- 11445124
TI  - France cautiously proposes research on embryos.

PMID- 11445125
TI  - Pathways for self-tolerance and the treatment of autoimmune diseases.
AB  - Antigen delivers both immunogenic and tolerogenic signals to lymphocytes. The
      outcome of antigen exposure represents a complex integration of the timing of
      antigen binding with signals from many other immunogenic and tolerogenic
      costimulatory pathways. A road map of these signalling pathways is only beginning
      to be charted, revealing the mechansim of action and limitations of current
      immunotherapeutic agents and the points of attack for new agents. Ciclosporin and
      tacrolimus interfere with tolerogenic signals from antigen in addition to
      blocking immunogenic signals, thus preventing active establishment of tolerance.
      Corticosteroids inhibit a key immunogenic pathway, NFkappaB, and more specific
      inhibitors of this pathway may allow tolerance to be actively established while
      immune responses are blocked. New experimental therapies aim to mimic tolerogenic
      antigen signals by chronically stimulating antigen receptors with antigen or
      antibodies to the receptor, or aim to block costimulatory pathways involving CD40
      ligand, B7, or interleukin 2. Obtaining the desired response with these
      strategies is unpredictable because many of these signals have both tolerogenic
      and immunogenic roles. The cause of autoimune diseases has been determined for
      several rare monogenic disorders, revealing inherited deficiencies in tolerogenic
      costimulatory pathways such as FAS. Common autoimmune disorders may have a
      biochemically related pathogenesis.

PMID- 11445126
TI  - Myasthenia gravis.

PMID- 11445128
TI  - Some workmen can blame their tools: artistic change in an individual with
      Alzheimer's disease.

PMID- 11445135
TI  - Imitation, mirror neurons and autism.
AB  - Various deficits in the cognitive functioning of people with autism have been
      documented in recent years but these provide only partial explanations for the
      condition. We focus instead on an imitative disturbance involving difficulties
      both in copying actions and in inhibiting more stereotyped mimicking, such as
      echolalia. A candidate for the neural basis of this disturbance may be found in a
      recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs).
      These neurons show activity in relation both to specific actions performed by
      self and matching actions performed by others, providing a potential bridge
      between minds. MN systems exist in primates without imitative and 'theory of
      mind' abilities and we suggest that in order for them to have become utilized to
      perform social cognitive functions, sophisticated cortical neuronal systems have
      evolved in which MNs function as key elements. Early developmental failures of MN
      systems are likely to result in a consequent cascade of developmental impairments
      characterised by the clinical syndrome of autism.

PMID- 11445136
TI  - Micro-nutrient supplementation and the intelligence of children.
AB  - A growing number of double-blind placebo-controlled studies have considered the
      influence of micro-nutrient supplementation on the intelligence of children.
      Earlier studies prevented the drawing of conclusions as they did not
      systematically approach the topic. However, over the last 10 years, a series of
      studies have compared the impact of supplementation on either verbal or non
      verbal measures of intelligence. In 10 out of 13 studies a positive response has
      been reported, always with non-verbal measures, in at least a sub-section of the
      experimental sample. A selective response to non-verbal tests was predicted as
      they reflect basic biologically functioning that could be expected to be
      influenced by diet. The evidence is that not all children respond to
      supplementation, rather there is a minority who benefit, whose diet offers low
      amounts of micro-nutrients. Such observations are consistent with dietary surveys
      that typically report a sub-set of children with a low intake. The topic is at a
      very early stage and needs the clarification gained from a series of large-scale
      studies that consider children of a wide range of ages, dietary styles and social
      backgrounds.

PMID- 11445137
TI  - Cognitive effects of insulin in the central nervous system.
AB  - Evidence has been accumulating recently that the hormone insulin may modulate
      cognitive activity by acting in the central nervous system. Initially derived
      from the observation that insulin and insulin receptors are found in specific
      brain areas, this evidence also includes cognitive assessments of humans in
      insulin-deficient and insulin-resistant disease states and experimental
      manipulation of rodent models. Additional support is derived from in vivo and in
      vitro systems that are used to investigate the neurophysiological basis of
      learning and memory. This article is a brief review of the literature that
      suggests a connection between insulin and memory and draws together some of the
      findings relevant to possible physiological mechanisms for this cognitive effect.

PMID- 11445138
TI  - Cognitive and behavioral assessment in experimental stroke research: will it
      prove useful?
AB  - Stroke in humans is associated with deficits in sensorimotor and cognitive
      function. Consequently, many stroke researchers recently have expanded their
      techniques to assess cognitive and behavioral correlates of histologically
      determined stroke damage in animal models. Although the incorporation of
      functional outcome assessment represents an important step forward in stroke
      research, reports of middle cerebral artery occlusion (MCAO) induced behavioral
      deficits often conflict, and a significant correlation between post-stroke
      histology and behavior has been reported in few stroke studies. Discrepancies in
      behavioral outcomes among studies may be due to several factors, such as method
      of MCAO, duration of occlusion, strain, the timing and method of the behavioral
      testing and the laboratory environment. Furthermore, proper experimental and
      control groups, necessary to rule out potential confounding factors during
      cognitive testing, often are not incorporated. The goal of this review is: (1) to
      provide a description of the techniques most commonly employed to assess
      functional outcome after (MCAO) in rodents and (2) to identify potential
      confounding factors that may interfere with a clear interpretation of the
      behavioral data.

PMID- 11445139
TI  - Opioid-NMDA receptor interactions may clarify conditioned (associative)
      components of opioid analgesic tolerance.
AB  - Recent evidence suggests that acute administration of opioid analgesic drugs
      (such as morphine or heroin) produces delayed hyperalgesia. This hyperalgesic
      response is likely to result from hyperactivation of NMDA receptors triggered by
      stimulation of opioid receptors and may mediate acute tolerance. In support of
      this hypothesis, blockade of NMDA receptors attenuates opioid-induced delayed
      hyperalgesia and prolongs the duration of antinociceptive activity of morphine.
      Furthermore, the NMDA receptor-induced hyperalgesia is likely an unconditioned
      response to opioid receptor stimulation that becomes spatiotemporally associated
      with environmental cues accompanying repeated opioid exposure. This hypothesis
      conforms to the traditional Pavlovian requirement for conditioned and
      unconditioned responses to be qualitatively similar. In support of the role of
      NMDA receptor hyperactivation in morphine tolerance, NMDA receptor antagonists
      have been shown to block development of analgesic tolerance induced by repeated
      exposures to morphine. The view of the conditioned nature of opioid tolerance may
      be significantly extended by assuming that upon repeated drug administration an
      early-onset effect of a drug may become a predictive stimulus for a later-onset
      effect and, consequentially, it may become empowered to elicit the later-onset
      effect itself. Such 'intra-drug' conditioning hypothesis is well in line with the
      current experimental evidence but further studies will be needed to verify it
      directly.

PMID- 11445140
TI  - The novelty P3: an event-related brain potential (ERP) sign of the brain's
      evaluation of novelty.
AB  - A review of the literature that examines event-related brain potentials (ERPs)
      and novelty processing reveals that the orienting response engendered by deviant
      or unexpected events consists of a characteristic ERP pattern, comprised
      sequentially of the mismatch negativity (MMN) and the novelty P3 or P3a. A wide
      variety of evidence suggests that the MMN reflects the detection of deviant
      events, whereas the P3a is associated more with the evaluation of those events
      for subsequent behavioral action. On the scalp, the novelty P3a is comprised of
      at least two aspects, one frontal the other posterior, each with different
      cognitive (and presumably neurologic) correlates. Intracranial ERP investigations
      and studies of patients with localized brain lesions (and, to some extent, fMRI
      data) converge with the scalp-recorded data in suggesting a widespread neural
      network, the different aspects of which respond differentially to stimulus and
      task characteristics.

PMID- 11445141
TI  - Optimization of recombinant adeno-associated virus production using an herpes
      simplex virus amplicon system.
AB  - A major limitation of adeno-associated virus (AAV) based vectors for clinical
      applications to date is the production of high-titer recombinant AAV vector
      stocks. Despite recent improvements, the amount of recombinant adeno-associated
      virus vectors (rAAV) particles produced per cell continues to be significantly
      lower than that of wild-type AAV. In this study, an HSV-based system for rAAV
      production was used to examine the influence of different parameters including
      transfection conditions (vector-to-packaging plasmid ratio, amount of total
      transfected DNA, cell confluency) and multiplicity of infection of herpes helper
      virus on the resulting titre of rAAV stocks. For herpes helper virus, time-course
      experiments were carried out to analyse the effect on rAAV yields up to 72 h
      postinfection and to determine the ideal harvesting time. Taken together, the
      optimized production scheme consistently yields more than 3x10(3) transducing
      units per producer cell.

PMID- 11445142
TI  - Improvements in methods for calculating virus titer estimates from TCID50 and
      plaque assays.
AB  - Calculation of titer estimates and use of titer reduction assays are fundamental
      approaches used by virologists. Titer assays being biological assays and based on
      limiting dilution methods require good error control, both methodologically and
      analytically. The need for good statistical analysis is likely to become even
      greater as in clinical, manufacturing, as well as the research settings, improved
      analytical criteria, quality control, and assurance standards are adopted.
      Furthermore, increasingly, virus titer assays are based on high throughput
      methods, which generate continuous rather than traditional quantal data.
      Described here are two different weighted linear regression methods to determine
      TCID50 and PFU titers from CPE assays. The TCID50 analysis makes use of a
      generalized least squares approach using continuous colorimetric data. The plaque
      analysis makes use of weighted least squares forced through the origin using
      quantal plaque data generated by serial dilutions. Both methods are improvements
      in titer and error estimation compared to simpler calculation methods. These
      methods may have greatest value when lack of experimental material or costs of
      analysis precludes extensive replicate titer determinations but good estimates of
      titers and/or treatment differences are essential.

PMID- 11445143
TI  - The diagnostic significance of an assay for 'total' hepatitis C core antigen.
AB  - A measurable serological response to hepatitis C infection is delayed on average
      until 70 days after infection. In addition, it may not occur in some
      immunocompromised people. Detection of free hepatitis C (HCV) core antigen in
      blood has enabled diagnosis in the pre-seroconversion period. The ability to
      detect 'total' HCV core antigen, both free and antibody bound, would widen its
      use for confirming anti-HCV antibody positive patients and monitoring a
      therapeutic response. This study has evaluated a prototype 'total' HCV core
      antigen immunoassay. Sera from 145 HCV negative blood donors gave a mean value of
      54.9 (+/-46.2) pg/ml based on recombinant antigen standards. Using these figures,
      the HCV core antigen cut-off was set as 200 pg/ml. Two hundred blood donors sera
      with indeterminant (a single-band on recombinant immunoblot assay) HCV antibody
      statuses gave fully concordant HCV core antigen results compared to their
      polymerase chain reactions (PCRs)--three positive, and 197 negative. HCV core
      antigen and PCR results were compared for 59 sera from 19 HCV positive liver
      disease patients. The HCV core antigen results were in complete agreement with
      their PCRs for the nine patients always PCR positive and the three continuously
      negative. For six patients on antiviral therapy whose qualitative PCRs changed
      from positive to negative, the HCV core antigen results paralleled the PCR
      results. The only discrepant results were from one patient whose PCR results went
      from negative to positive. 'Total' HCV core antigen testing will greatly improve
      the scope of diagnostic tests for hepatitis C.

PMID- 11445144
TI  - Quantitative competitive NASBA for measuring mRNA expression levels of the
      immediate early 1, late pp67, and immune evasion genes US3, US6 and US11 in cells
      infected with human cytomegalovirus.
AB  - Different cell types were infected with human cytomegalovirus (HCMV) and RNA
      expression dynamics were analyzed by quantitative NASBA assays for IE1 (UL123),
      pp67 (UL65) and the immune evasion genes (US3, US6 and US11). The quantitative
      NASBA assays gave reproducible quantification in the range of 10(3)-10(6) RNA
      copies for IE1 and pp67 RNA, from 3x10(3) to 1x10(6) RNA copies for US6 and US11
      RNA, and from 1x10(4) to 1x10(6) RNA copies for US3 RNA. SMC, HAEC and HUVEC
      cells infected with an, in endothelial cells, propagated HCMV strain (VHL/E)
      showed similar RNA expression dynamics for the analyzed genes. Expression of all
      genes studied was observed within the first 4 h post-infection. The first gene
      for which expression could be detected was IE1, followed by US3, US11, pp67 and
      US6. Fibroblasts infected with HCMV strain AD169 showed a different RNA
      expression pattern for US3. Translation of the mRNA studied was demonstrated by
      detection of the proteins 48 h post-infection by immunofluorescence.

PMID- 11445145
TI  - RT-PCR for detecting five distinct Tospovirus species using degenerate primers
      and dsRNA template.
AB  - RT-PCR procedures for detection of multiple species of tospovirus from plant
      tissues were investigated. Downstream primers were designated from the 3'
      untranslated sequences of the S RNA. An upstream primer was designated from the
      degenerated sequences of the nucleocapsid protein. Approximately 450 bp DNA
      fragments were detected when Tomato spotted wilt virus (TSWV)- or Impatiens
      necrotic spot virus (INSV)- infected tissues were examined. Approximately 350 bp
      DNA fragments were detected when Watermelon silver mottle virus (WSMoV)- or Melon
      yellow spot virus (MYSV)-infected tissues were examined. Template RNA was
      extracted using CF 11 cellulose powder, and nonspecific amplification became
      unnoticeable when double-stranded RNA was used. The amplified fragments of WSMoV
      were differentiated from those of MYSV by AluI or TaqI digestion. The amplified
      fragments of TSWV were differentiated from those of INSV by DraI or HindIII
      digestion. An alstroemeria plant that was infected with an unidentified
      tospovirus was also examined, and a 350 bp fragment that was 97% identical to
      Iris yellow spot virus was detected. This method, therefore, detected at least
      five distinct Tospovirus species.

PMID- 11445146
TI  - Human cytomegalovirus infection: diagnostic potential of recombinant antigens for
      cytomegalovirus antibody detection.
AB  - Recombinant antigen-based enzyme immunoassays (EIAs) for the detection of human
      cytomegalovirus (HCMV) specific antibody are believed to yield a higher
      sensitivity and specificity than virus lysate EIAs. The aim of the present study
      was to evaluate the accuracy of newly established HCMV assays (Copalis CMV
      Multiplex, Sorin; Cobas Core CMV IgG and IgM EIAs, Roche Diagnostics; Anti-HCMV
      recombinant IgG, gB-IgG, IgM and IgA, Biotest; and ETI-CYTOK-G PLUS and M reverse
      PLUS, Sorin) based on recombinant antigens and/or virus lysate for laboratory
      diagnosis of HCMV infection. For the assessment of sensitivity, follow-up samples
      from patients suffering from active HCMV infection were tested. Testing a large
      number of potentially interfering samples challenged the specificity of the
      assays. There was no statistically significant difference in the performance of
      HCMV IgG assays. The results were more heterogeneous for the detection of
      serological markers of active infection (HCMV IgM, HCMV IgA and anti-CM2). The
      sensitivities of the different assays ranged between 40.5 and 71.4%. A variable
      number (17.8-1.7%) of false-positive results were obtained among potentially
      interfering serum samples. Two of the recombinant antigen based assays showed a
      high degree of interference with EBV VCA-IgM-positive sera. The best performance
      was achieved with ETI-CYTOK-M reverse PLUS since it combined the highest
      sensitivity with specificity. Commercially available assays based on recombinant
      antigens showed, overall, a poorer performance than the virus lysate EIA.

PMID- 11445147
TI  - Amplification and cloning of the full-length genome of Japanese encephalitis
      virus by a novel long RT-PCR protocol in a cosmid vector.
AB  - A novel and rapid full-length long RT-PCR technique was established to produce
      genome-length cDNA from Japanese encephalitis virus. In vitro positive strand RNA
      transcripts from the full-length RT-PCR amplicon including T7 promoter sequences
      at the 5' end were proved to be infectious upon transfection. The full-length
      amplicon without the T7 promoter was cloned into a cosmid vector under the SP6
      promoter. This stable clone, designated as pJEV-1, was characterised further and
      used as a genetic resource for generation of infectious RNA transcripts, gene
      manipulation and expression. The 'run-off' transcript from pJEV-1 with vector
      sequences at the either end of the insert was not infectious, but transcripts of
      the full-length PCR amplicon from pJEV-1 produced infectious virus upon
      transfection. A transcript with an engineered Xho I site from two ligated PCR
      fragments amplified from pJEV-1 was also infectious. Furthermore, the coding
      region for premembrane and envelope proteins (preM-E) from pJEV-1 was subcloned
      and expressed in the Drosophila Expression System. The expressed protein showed
      correct molecular size and was immunoreactive with a Japanese encephalitis virus
      E protein-specific antibody. The derivation of genome-size cDNA from Japanese
      encephalitis virus and the stable clone will facilitate investigation of this
      virus and elucidation of its pathogenesis at the molecular level.

PMID- 11445148
TI  - A quantitative GFP-based bioassay for the detection of HIV-1 Tat transactivation
      inhibitors.
AB  - The Tat function of the human immunodeficiency virus (HIV) represents an
      important target for the development of new anti-HIV drugs. A rapid, sensitive
      and simple bioassay was developed for the detection of HIV transactivation
      inhibitors. A reporter plasmid based on the expression of the green fluorescent
      protein (GFP) under control of the HIV-1 long terminal repeat (LTR) was
      constructed. This reporter gene can be quantified by simply measuring the
      fluorescence irradiated by GFP-producing cells, without the need of extraction
      procedures or enzymatic assays. Cells, stably expressing HIV-1 Tat protein, were
      transfected with this plasmid and the inhibitory effect of anti-Tat drugs was
      assessed by measuring the inhibition of fluorescence. Using this assay system the
      anti-transactivation activity of several known compounds was confirmed. This is
      the first HIV transactivation assay using GFP reporter gene in microtiter plates.
      The assay can be used for the detection and quantification of HIV
      transactivation, and for the high throughput evaluation of anti-transactivation
      drugs in different cellular backgrounds.

PMID- 11445149
TI  - Development of a rapid chromatographic strip test for the pen-side detection of
      foot-and-mouth disease virus antigen.
AB  - Foot-and-mouth disease (FMD) is the most contagious animal virus disease of
      cloven-hoofed livestock and requires reliable and accurate diagnosis for the
      implementation of measures to control effectively its spread. Routine diagnosis
      of FMD is carried out at the OIE/FAO World Reference Laboratory for Foot-and
      Mouth Disease (WRL for FMD), Pirbright by the combined use of ELISA and virus
      isolation in cell culture supplemented by reverse transcription polymerase chain
      reaction (RT-PCR) methods. These techniques require skilled personnel and
      dedicated laboratory facilities which are expensive. The development of a rapid
      and simple test for the detection of FMD virus antigen using Clearview
      chromatographic strip test technology for field application is described. This
      device detected FMD viral antigen in nasal swabs, epithelial suspensions and
      probangs from clinical samples submitted from the field, from animals infected
      experimentally and in supernatant fluids resulting from their passage in cell
      culture. The test system was more sensitive than ELISA for the diagnosis of all
      seven serotypes of FMD virus in the epithelial suspensions and nasal swabs and
      had equivalent sensitivity to the ELISA for the detection of contemporary virus
      strains in cell culture supernatant fluids. The study demonstrated the potential
      for this device to confirm a clinical diagnosis at the site of a suspected FMD
      outbreak, thereby offering the possibility of implementing control procedures
      more rapidly. Such pen-side diagnosis would have particular benefits in FMD
      emergencies, relevance to FMD control programmes which operate in endemic regions
      of the world such as South East Asia and for increasing disease awareness in
      other areas where efforts to control disease may be difficult. In each
      circumstance the availability of a pen-side device for diagnosis would reduce the
      necessity for sending routine diagnostic samples to an FMD laboratory and thereby
      reduce the delay in diagnosis, which can in some areas be considerable.

PMID- 11445150
TI  - Limitations and improvements of the quantiplex branched-DNA assay in Hepatitis B
      virus-infected patients receiving lamivudine.
AB  - The branched DNA (bDNA) assay for hepatitis B virus (Chiron Corporation
      Emerville, USA) was investigated by application to HBV-infected patients in
      Taiwan, where the B and C genotypes of hepatitis B virus are most prevalent. The
      study group included sera with hepatitis B surface antigen (HBsAg) and e antigen
      (HBeAg); Group 1 (n=70) without treatment; Group 2 (n=28) lamivudine treatment
      less than 3 months; Group 3 (n=73) lamivudine treatment 3-12 months; Group 4
      (n=45) HBeAg-negative sera after 1 year treatment with lamivudine; control group
      (n=36) HBsAg-negative sera. Comparison of identical-sample results showed a
      significantly higher coefficient of variation for low-level HBV DNA (<100 MEq/ml)
      than for high-level (> or =100 MEq/ml), indicating increasing assay inaccuracy
      uncertainty as the sample HBV DNA concentration decreased. It is thus concluded
      that low-titered sera should receive special careful pipetting and processing. It
      was also found that using the relative luminescence of the negative control plus
      two standard deviations (S.D.) as a new cutoff could promote sensitivity (97.1-
      >97.1%, 89.3-->100%, 76.7-->84.9%, and 17.8-->22.2% in Groups 1-4, respectively)
      and specificity (94.4-->97.2%). In summary, the bDNA HBV assay showed only
      moderate assay performance for samples with low HBV DNA levels. This problem can
      be improved partially by choosing a new cutoff value based on the relative
      luminescence of the negative controls in the kit.

PMID- 11445151
TI  - Testing for clinical anaemia caused by Haemonchus spp. in goats farmed under
      resource-poor conditions in South Africa using an eye colour chart developed for
      sheep.
AB  - A novel clinical assay for the assessment and subsequent treatment of Haemonchus
      infection in sheep to slow down the development of anthelmintic resistance--the
      FAMACHA system--has been developed, tested and validated in South Africa. The
      system is based on a colour chart with five colour categories depicting varying
      degrees of anaemia that are compared with the colour of the mucous membranes of
      the eyes of sheep. The animal is then scored from severely anaemic (pale) through
      anaemic to non-anaemic (red) and those animals considered in danger of succumbing
      to the effects of haemonchosis are treated. This method was tested in goats
      farmed under resource-poor conditions in South Africa. Analyses in goats
      performed during the summers of 1998/1999 and 1999/2000 show a test sensitivity
      of 76 and 85%, respectively, meaning that the system may be used to identify
      correctly 76-85% of those animals in need of treatment with an anthelmintic.
      However, the test specificity remains low at 52-55%. This means that a large
      proportion of those animals that would not require treatment would in fact be
      treated. However, when the use of the FAMACHA system is compared with
      conventional dosing practices where all the animals are treated, using the
      FAMACHA system would result in a large proportion of the animals being left
      untreated. The untreated animals are then able to deposit the eggs of
      anthelmintic-susceptible worms on the pasture, while the treated ones should pass
      very few ova, given an effective anthelmintic. This maintains a reservoir of
      susceptible larvae in refugia, and should slow down the development of
      anthelmintic resistance. The validation of the FAMACHA system for goats for use
      by resource-poor farmers, which this paper describes, may have wide application
      in the tropics and subtropics of sub-Saharan Africa and elsewhere.

PMID- 11445152
TI  - Effectiveness of grazing management in controlling gastrointestinal nematodes in
      weaner lambs on pasture in Denmark.
AB  - A dose and move to clean pasture strategy for nematode control in weaner sheep
      was compared to a move only strategy. Sixteen ewes with twin lambs (2-3 weeks
      old) were turned out on infected pasture on 4 May 1999. On 1 July, the lambs were
      allocated to four groups of eight and weaned on to clean pasture. Two groups
      (DM1+2) were treated with anthelmintics, while the other two (M1+2) were not
      treated. Each group was allocated to a separate paddock and set stocked until 27
      September when all the animals were slaughtered to perform worm counts. Moving
      the weaned lambs to clean pasture reduced the faecal egg counts to less than one
      third within 4 weeks while the treatment reduced it to zero for 4 weeks. Faecal
      egg counts of the dose and move groups remained significantly lower for 6 weeks
      (P<0.0001) after moving to the clean pasture. After this period the differences
      were not significant as the dose and move groups started shedding eggs in faeces.
      The pasture infectivity was lower in the paddocks grazed by groups (DM1+2). The
      weight gains and the serum albumin levels were comparable in all four groups. O.
      circumcinta and Trichostrongylus vitrinus were the major species recovered. The
      total worm counts were significantly lower in (DM1+2) compared to M1+2,
      particularly the mean counts in the small intestines (T. vitrinus) (P<0.01). It
      was concluded that weaning lambs at the beginning of July and moving them before
      the expected mid-summer rise in herbage infection to a clean pasture will prevent
      parasitic gastroenteritis and achieve good production whether the move is
      accompanied by anthelmintic treatment or not. The effects will be subject to
      prevailing nematode species, local climatic conditions and length of the grazing
      season.

PMID- 11445153
TI  - Comparative efficacy, persistent effect, and treatment intervals of anthelmintic
      pastes in naturally infected horses.
AB  - Eighty horses were involved in a comparative, controlled, and randomised field
      study conducted in Australia and Brazil. This study was undertaken to address the
      duration of efficacy (by faecal egg count reduction) of four anthelmintic pastes
      and to measure the time required between treatments on horses naturally infected
      by gastrointestinal nematodes. The treatment interval was based on the egg
      reappearance period (ERP), defined as "the period after treatment when horses
      have reached a positive egg count equal or superior to 200 eggs per gram (epg) of
      faeces". Horses were ranked according to pre-treatment faecal egg counts and
      randomly allocated on Day 0 to one of the four treatment groups (n=16). Group A
      received a combination of ivermectin at 200 microg/kg and praziquantel at
      1.5mg/kg, Group B received an ivermectin paste at 200 microg/kg, Group C received
      a reference product containing ivermectin at 200 microg/kg, Group D received a
      moxidectin paste at 400 microg/kg, and Group E received a placebo. Horses were
      individually faecal sampled at weekly interval from Days 0 to 70 after treatment
      and coprocultures were made on pooled samples at the pre-treatment time on D-7 in
      Brazil and D-6 in Australia. The nematode population was mainly composed of small
      strongyles (Cyathostominae, Gyalocephalus spp., Triodontophorus spp.). All
      products were efficient (>90% efficacy) until Day 42 with no statistical
      difference between groups. From Day 49 onwards, Group C reached the threshold,
      while Group B exceeded this threshold on Day 56. Groups A and D remained below
      200 epg for the entire study period (70 days). The interval between two
      anthelmintic treatments can vary according to the threshold. The ERP was defined
      as the period after treatment while the output of eggs is negligible or
      considered as acceptable. The mean number of days calculated to recurrence of 200
      epg and more was, respectively, 60 days for product A, 56 days for products B and
      C, and 64 days for product D. If treatments are combined with other methods of
      limiting exposure to infective larvae on pasture, the number of treatments
      required will be reduced even further.

PMID- 11445154
TI  - Efficacy of a single whole-body spray treatment of spinosad, against Boophilus
      microplus (Acari: Ixodidae) on cattle.
AB  - The efficacy of a single whole-body spray of spinosad, a naturally derived
      control agent, applied at three concentrations was evaluated against cattle
      infested three separate times prior to treatment and at four weekly intervals
      following treatment with Boophilus microplus (Canestrini). At 0.0167% active
      ingredient (AI) both tick numbers (1894 ticks per calf) and index of fecundity
      (IF) of females (258.3) were no different than that of the control group.
      However, spinosad treatment at both 0.05 and 0.15% AI resulted in fewer ticks per
      calf (600 and 935, respectively) with lower IF values for females (43.4 and 38.4,
      respectively). The percent control of ticks on the animals at the time of
      treatment (acute efficacy) was dramatically lower at 0.0167% AI (21.4%) than at
      0.05 (86.3%) and 0.15% AI (87.9%). Spinosad treatments appeared to be more
      effective against immature stages (nymphs and larvae) than against adult ticks
      that were on the animals at the time of treatment. The mean weight of females
      that survived to repletion was similar (322-348 mg) in all groups. By contrast,
      the mean weight of egg masses produced by females was highest in the control
      group (155 mg), whereas each increase in spinosad concentration resulted in a
      substantial decrease in egg mass weight, with the 0.15% AI group averaging only
      73 mg. The hatch rate of eggs derived from females ranged from 93.4% in control
      females down to 53.9% hatch for females treated at 0.15% AI spinosad. The
      residual efficacy of spinosad at 0.0167% AI was poor even at 1 week following
      treatment, resulting in 101 ticks per calf and a level of control of only 66.4%.
      At 0.05% AI, protection against successful reinfestation was high at 1-week post
      treatment where only five ticks per calf reached repletion, and control of the IF
      of these females was 99.3%. The 0.15% AI treatment provided almost complete
      protection against reinfestation for 2 weeks following treatment (< or =5 ticks
      per calf), and control of the IF of these ticks was >99.9%. Thus, the use of
      spinosad at US ports-of-entry would be unacceptable because of the critical
      necessity of achieving 100% control with a single treatment to prevent the
      reintroduction of ticks. However, it is likely ticks could be eradicated using
      spinosad in tick infested areas of the US if repeated (systematic) treatments
      were applied to cattle maintained on the premises.

PMID- 11445155
TI  - Salivary gland extract of Rhipicephalus appendiculatus ticks inhibits in vitro
      transcription and secretion of cytokines and production of nitric oxide by LPS
      stimulated JA-4 cells.
AB  - There is increasing evidence that compounds in tick saliva and salivary gland
      extract (SGE) have a suppressive effect on host immunity and that tick-borne
      pathogens exploit this situation to their benefit thus causing diseases. We have
      demonstrated that SGE derived from Rhipicephalus appendiculatus ticks has a
      suppressive effect on a macrophage like cell line, JA-4, in terms of secretion as
      well as mRNA transcription of three cytokines. Percent suppression of cytokine
      secretion by JA-4 cells cultured in the presence of lipopolysaccharide (LPS) and
      SGE in comparison to JA-4 cells cultured in the presence of LPS alone was 67.8,
      89.1 and 82.0% for IL-1alpha, TNF-alpha and IL-10, respectively (P<0.05). A
      similar pattern of results was demonstrated in terms of mRNA transcription where
      SGE-induced suppression was 36.9% for IL-1alpha, 25.0% for TNF-alpha and 31.5%
      for IL-10 (P<0.05). In addition, we have demonstrated that SGE partially
      inhibited nitric oxide production by JA-4 activated with LPS. The results of the
      present study suggest that tick salivary gland compounds may exert their effect
      in vivo by blocking the functions of macrophages in the transcription of
      cytokines and production of nitric oxide. This SGE-induced immunomodulation may
      comprise a major gateway in the facilitation of tick feeding and transmission of
      pathogens in hosts.

PMID- 11445156
TI  - Dynamics of IgG1 and IgG2 subclass response in dogs naturally and experimentally
      infected with Ehrlichia canis.
AB  - Immunoglobulin (Ig) G subclasses were measured in dogs naturally and
      experimentally infected with Ehrlichia canis using enzyme-linked immunosorbant
      assay (ELISA). In this study, a higher IgG2 subclass response was noticed to
      natural and experimental E. canis infection in dogs. Anti-E. canis-IgG2 optic
      density (OD) values were found to be significantly higher than anti-E. canis-IgG1
      during the different phases of the disease, and no differences in the IgG
      subclass responses to E. canis infection were found between symptomatic and
      asymptomatic dogs. Doxycycline treatment, which eliminated the rickettsia in
      three of four persistently infected dogs, had no noticeable influence on the E.
      canis-IgG subclass OD values during the treatment period. In order to facilitate
      the study, an ELISA for the detection of anti-E. canis IgG was developed and was
      shown to be sensitive and specific for E. canis-IgG, and in a significant
      correlation with the indirect immunofluorescence antibody test.

PMID- 11445157
TI  - Experimental infection with Tritrichomonas suis in heifers.
AB  - Nine heifers were intravaginally challenged with 9.3x10(6) Tritrichomonas suis
      reference strains. Vaginal mucus and serum samples were collected weekly 4 weeks
      post-inoculation. Vaginal mucus was cultured for T. suis and sera was tested by
      ELISA against whole cell antigens for T. suis and Tritrichomonas foetus. All
      vaginal mucus cultures were T. suis-negative during the experiment. ELISA values
      for both antigens were similar and differences were not significant (P>0.05).
      Positive control serum samples from one heifer vaccinated against T. foetus
      showed anti-T. suis ELISA values. We concluded that T. suis intravaginal
      inoculation induced a low level of serum immune response in heifers measured by
      ELISA and both protozoa probably share a common antigen. However, under the
      experimental conditions of this trial, colonization of the heifers' genital tract
      was not possible in any of the nine animals.

PMID- 11445158
TI  - Excretion of Cryptosporidium oocysts by goats in relation to age and season in
      the dry zone of Sri Lanka.
AB  - Pattern of Cryptosporidium oocyst shedding in relation to age and season was
      investigated monthly from May 1999 to April 2000 in three groups (24 goats per
      group) of naturally infected goats (from 1 month of age). The three groups
      designated 1, 2 and 3 were studied for 12, 6 and 3 months, respectively. An
      association between Cryptosporidium oocyst counts and age was demonstrated. In
      Group 1, oocyst excretion in the first, second and fourth months of age were
      significantly higher than that in 6, 7, 8, 9 and 12 months of age (p<0.01),
      whereas in Group 2, oocyst excretion in the first month of age was significantly
      higher than that in 2, 4, 5 and 6 months of age (p<0.01). The 3-month
      observations made in Group 3 showed high oocyst excretion during 1 and 3 months
      of age. The mean maximum count for Group 1 was 592 oocyst per gram of feces when
      the animals were 2 months old, while in Groups 2 and 3, this was observed at 3
      months of age and the oocyst counts were 787 and 520, respectively. A close
      association between the prevalence of the Cryptosporidium infection and age of
      the animal was also observed (p<0.01). At least one-third of the Group 1 animals
      were excreting Cryptosporidium oocysts during the first 5 months of age. Goats
      excreted Cryptosporidium oocysts irrespective of the dry or rainy season. The
      long periods of Cryptosporidium oocyst shedding by goats may have implications
      for the epidemiology of the disease in susceptible hosts.

PMID- 11445159
TI  - Bacterial virulence: can we draw the line?
AB  - The molecular approach to microbial pathogenesis has resulted in an impressive
      amount of data on bacterial virulence genes. Bacterial genome sequences rapidly
      add candidate virulence genes to electronic databases. The interpretation of this
      overwhelming information is obscured because every gene involved in pathogenicity
      is called a virulence gene, regardless of its function in the complex process of
      virulence. This review summarizes the changing concept of bacterial virulence and
      the detection and identification strategies followed to recognize virulence
      genes. A refined definition of virulence genes is proposed in which the function
      of the gene in the virulence process is incorporated. We propose to include the
      life-style of bacteria in the assessment of their putative virulence genes. A
      universal nomenclature in analogy to the EC enzyme numbering system is proposed.
      These recommendations would lead to a better insight into bacterial virulence and
      a more precise annotation of (putative) virulence genes, which would enable more
      efficient use of electronic databases.

PMID- 11445160
TI  - What makes the bacteriophage lambda Red system useful for genetic engineering:
      molecular mechanism and biological function.
AB  - Recent studies have generated interest in the use of the homologous recombination
      system of bacteriophage lambda for genetic engineering. The system, called Red,
      consists primarily of three proteins: lambda exonuclease, which processively
      digests the 5'-ended strand of a dsDNA end; beta protein, which binds to ssDNA
      and promotes strand annealing; and gamma protein, which binds to the bacterial
      RecBCD enzyme and inhibits its activities. These proteins induce a 'hyper-rec'
      state in Escherichia coli and other bacteria, in which recombination events
      between DNA species with as little as 40 bp of shared sequence occur at high
      frequency. Red-mediated recombination in the hyper-rec bacterium proceeds via a
      number of different pathways, and with the involvement of different sets of
      bacterial proteins, depending in part on the nature of the recombining DNA
      species. The role of high-frequency double-strand break repair/recombination in
      the life cycle of the lambdoid phages is discussed.

PMID- 11445161
TI  - Spontaneous mutations affecting transcriptional regulation by protocatechuate in
      Acinetobacter.
AB  - Positive selection yields Acinetobacter strains with a spontaneous mutation
      blocking catabolism of protocatechuate. For this study, the growth temperature
      during selection was lowered to 22 degrees C: growth at 37 degrees C was found to
      mask the role of the protocatechuate-responsive transcriptional regulator PcaU.
      The resulting mutants included those with amino acid substitutions useful for
      understanding PcaU structure and function, a 20-bp deletion whose repeated
      isolation suggested genetic instability of DNA in the putative PcaU operator, and
      a large deletion whose phenotype revealed that the supraoperonic cluster of genes
      for the protocatechuate branch of the beta-ketoadipate pathway extends to genes
      for the utilization of C(6)-C(10) straight-chain dicarboxylic acids including
      adipate.

PMID- 11445162
TI  - Beta-galactofuranoside glycoconjugates on conidia and conidiophores of
      Aspergillus niger.
AB  - Galactose in the furanoic conformation appears to be limited to bacteria and
      lower eukaryotes. Galactofuranoic (Galf)-containing glycoconjugates that occur in
      organisms pathogenic or allergenic to man are frequently antigenic and
      immunodominant. We have used an immunochemical approach, employing a monoclonal
      antibody that recognises Galf epitopes, to investigate the presence of Galf
      containing glycoconjugates within conidia and conidiophores of Aspergillus niger.
      ELISA and immunofluorescence microscopy indicated that specific and saturable
      binding sites were found on both. Inhibition studies confirmed that this binding
      was to Galf-containing glycoconjugates. Interestingly, the conidiophore heads
      were particularly rich in these glycoconjugates. Western blotting identified a
      Galf glycoprotein of 150-200 kDa from disrupted conidia.

PMID- 11445163
TI  - Functional analysis of the Bacillus subtilis cysK and cysJI genes.
AB  - The function of the Bacillus subtilis cysK and cysJI (previously designated
      yvgQR) genes, expected to be involved in the assimilatory sulfate reduction
      pathway, was investigated. A B. subtilis mutant with a deletion in the cysJI
      genes was unable to use sulfate or sulfite as sulfur source, which confirmed that
      these genes encode sulfite reductase. A mutant with a transposon insertion in the
      cysK gene, whose deduced protein sequence showed similarity to cysteine
      synthases, grew poorly on sulfate and butanesulfonate. A strain in which cysK and
      yrhA, a cysK paralog, were inactivated was unable to grow with sulfate. Whereas
      expression of the cysJI genes was induced by sulfate, expression of cysK was
      repressed both by sulfate and by cysteine.

PMID- 11445164
TI  - Substitution of Thr for Ala-237 in TEM-17, TEM-12 and TEM-26: alterations in beta
      lactam resistance conferred on Escherichia coli.
AB  - Non-naturally occurring mutants of TEM-17 (E104K), TEM-12 (R164S) and TEM-26
      (E104K:R164S) extended-spectrum (ES) beta-lactamases bearing threonine at
      position 237 were constructed by site-specific mutagenesis and expressed under
      isogenic conditions in Escherichia coli. Quantification of beta-lactamase
      activities and immunoblotting indicated that Ala-237-->Thr did not significantly
      affect expression levels of these ES enzymes. Minimum inhibitory concentrations
      of beta-lactam antibiotics showed that the presence of threonine at position 237
      exerted a dominant effect increasing the enzymes' preference for various early
      generation cephalosporins over penicillins. Activity against broad-spectrum
      oxyimino-beta-lactams was also changed. The effect of Ala-237-->Thr on the
      activity against ceftazidime, aztreonam, cefepime and cefpirome of all three ES
      TEM enzymes was detrimental. Introduction of Thr-237 improved activity against
      cefotaxime and ceftriaxone in TEM-12 and TEM-26, but not in TEM-17.

PMID- 11445165
TI  - Novel alcohol dehydrogenase activity in a mutant of Salmonella able to use
      ethanol as sole carbon source.
AB  - We selected a mutant of Salmonella enterica serovar Typhimurium that is capable
      of growing in air on ethanol as sole carbon and energy source. This adhI mutant
      expressed high levels of a novel alcohol dehydrogenase (AdhI) that uses ethanol,
      1-propanol and 2-propanol as substrates. The fermentative AdhE alcohol
      dehydrogenase was not expressed aerobically in the adhI mutant. Anaerobically,
      both the novel AdhI enzyme and the AdhE were expressed simultaneously in the adhI
      mutant. However, the adhI mutant showed no alteration in the composition of the
      fermentation products. In addition we found that both the parental Salmonella and
      its alcohol using adhI mutant expressed substantial levels of a dye-linked
      aldehyde dehydrogenase that is presumably responsible for conversion of
      acetaldehyde to acetate. This contrasts with the situation in Escherichia coli
      where mutants able to grow on ethanol express high aerobic levels of the AdhE
      enzyme, which performs both the alcohol dehydrogenase and aldehyde dehydrogenase
      reactions.

PMID- 11445166
TI  - Marinobacter strain NCE312 has a Pseudomonas-like naphthalene dioxygenase.
AB  - One strain of bacteria, designated NCE312, was isolated from a naphthalene
      digesting chemostat culture that was inoculated with creosote-contaminated marine
      sediment. The strain was isolated based on its ability to grow using naphthalene
      as a sole carbon source. In addition, the strain degraded 2-methylnaphthalene and
      1-methylnaphthalene. Analysis of a 16S rRNA gene sequence from NCE312 placed the
      isolate in the genus Marinobacter. Degenerate PCR primers were used to amplify a
      fragment of a naphthalene 1,2-dioxygenase large subunit gene. A phylogenetic
      analysis indicated the Marinobacter naphthalene dioxygenase is similar to those
      from Pseudomonas and Burkholderia strains suggesting that the dioxygenase gene
      may have been transferred horizontally between these lineages of bacteria.

PMID- 11445167
TI  - Relaxed rrn expression and amino acid requirement of a Corynebacterium glutamicum
      rel mutant defective in (p)ppGpp metabolism.
AB  - The stringent response in Corynebacterium glutamicum was investigated. Sets of
      rrn-cat fusions were constructed in their native chromosomal position to examine
      the effects of amino acid starvation in a rel(+) strain and a Deltarel mutant
      defective in (p)ppGpp metabolism. The expression of the six rrn operons in the
      rel(+) control was stringently regulated and reduced to 79% upon induction of
      amino acid starvation. The Deltarel mutant displayed a relaxed regulation and was
      unable to reduce the rrn expression under amino acid depletion conditions. In
      addition, the Deltarel mutant grew more slowly in minimal medium than a rel(+)
      control. This growth effect was restored by a plasmid-encoded copy of rel or,
      alternatively, by supplementation of the minimal medium with the amino acid
      mixture casamino acids. In particular, the Deltarel strain of C. glutamicum
      displayed a requirement for the amino acids histidine and serine.

PMID- 11445168
TI  - Cloning and characterisation of a hyp gene cluster in the filamentous
      cyanobacterium Nostoc sp. strain PCC 73102.
AB  - Maturation of [NiFe]-hydrogenases requires the action of several groups of
      accessory genes. Homologues of one group of these genes, the so-called hyp genes,
      putatively encoding proteins participating in the formation of an active uptake
      hydrogenase in the filamentous, heterocyst-forming cyanobacterium Nostoc PCC
      73102, were cloned. The cluster, consisting of hypF, hypC, hypD, hypE, hypA, and
      hypB, is located 3.8 kb upstream from the uptake hydrogenase-encoding hupSL. Gene
      expression analyses show that these hyp genes are, like hupL, transcribed under
      N(2)-fixing but not under non-N(2)-fixing growth conditions. Furthermore, the six
      hyp genes are transcribed together with an open reading frame upstream of hypF,
      as a single mRNA. Analysis of the DNA region upstream of the experimentally
      determined transcriptional start site revealed putative -10 and -35 sequence
      elements and putative binding sites for the global nitrogen regulator NtcA.

PMID- 11445169
TI  - Classification of trypanosomatids from fruits and seeds using morphological,
      biochemical and molecular markers revealed several genera among fruit isolates.
AB  - Trypanosomatids are widespread in several plant families and although most
      isolates have been classified as Phytomonas, other trypanosomatid genera can also
      infect plants. In order to assess the natural occurrence of non-Phytomonas
      trypanosomatids in plants we characterized 21 new trypanosomatid cultures, 18
      from fruits and three from seeds of 17 plant species. The trypanosomatids from
      fruit and seeds were compared in terms of morphological, growth, biochemical and
      molecular features. The high diversity among the isolates permitted the
      classification of the new flagellates into the genera Crithidia and Leptomonas as
      well as Phytomonas. The data showed that natural fruit infection with non
      Phytomonas trypanosomatids is more common than usually thought, being detected in
      43% of the fruit isolates.

PMID- 11445170
TI  - Purification and properties of Aquifex aeolicus DNA polymerase expressed in
      Escherichia coli.
AB  - The gene encoding Aquifex aeolicus (Aae) DNA polymerase was expressed under the
      control of the trp promoter on a high-copy plasmid, pTRPNS, in Escherichia coli.
      The expressed enzyme was purified 11-fold with a 13.8% yield and a specific
      activity of 2268.3 U mg(-1). The optimum pH of the enzyme was 6.8-7.2. The
      optimal concentrations of KCl and Mg(2+) were 20-30 mM and 4-5 mM, respectively.
      Aae DNA polymerase contained a double-strand-dependent 3'-->5' proofreading
      exonuclease activity but lacked any detectable 5'-->3' exonuclease activity.

PMID- 11445171
TI  - Evidence for polyphyletic origin of the members of the orders of Oscillatoriales
      and Pleurocapsales as determined by 16S rDNA analysis.
AB  - Phylogenetic analyses were carried out on six pleurocapsalean strains and 12
      oscillatorialean strains by sequence determination of the 16S rDNA (16S rRNA
      gene). Although heterocyst-forming strains of the orders Nostocales and
      Stigonematales were shown to be monophyletic, unicellular strains of the orders
      Chroococcales and filamentous Oscillatoriales were shown to be polyphyletic, as
      reported earlier. Moreover, unicellular and baeocyte-forming strains of the order
      Pleurocapsales, which were thought to be monophyletic, were newly found to be
      polyphyletic. The results strongly indicate that even morphology was not
      necessarily reflected in the phylogenetic relationships at the order level. A
      need exists to reconstruct the taxonomy of cyanobacteria at the order level.

PMID- 11445172
TI  - UP-PCR cross blot hybridization as a tool for identification of anastomosis
      groups in the Rhizoctonia solani complex.
AB  - A universally primed (UP)-PCR cross hybridization assay was developed for rapid
      identification of isolates of Rhizoctonia solani into the correct anastomosis
      group (AG). Twenty-one AG tester isolates belonging to 11 AGs of R. solani were
      amplified with a single UP primer which generated multiple PCR fragments for each
      isolate. The amplified products were spotted onto a filter, immobilized and used
      for cross hybridization against amplification products from the different
      isolates. Isolates within AG subgroups cross hybridize strongly, whereas between
      different AGs little or no cross hybridization occurs. Sixteen Rhizoctonia
      isolates from diseased sugar beets and potatoes were identified using the assay.
      The results were supported by restriction fragment length polymorphism analysis
      of the ITS1-5.8S-ITS2 region of the nuclear encoded ribosomal DNA. Through
      standardization and use of quick non-radioactive labeling techniques, the UP-PCR
      cross hybridization assay has potential for routine use by modern DNA chip
      technology.

PMID- 11445173
TI  - Glutamine synthetases of Corynebacterium glutamicum: transcriptional control and
      regulation of activity.
AB  - Regulation of glnA expression and glutamine synthetase I activity was analyzed in
      Corynebacterium glutamicum. Transcription is regulated by the global repressor
      protein AmtR, essential for derepression of glnA transcription are GlnK and
      uridylyltransferase, key proteins of the C. glutamicum nitrogen regulatory
      system. Glutamine synthetase I activity is controlled by
      adenylylation/deadenylylation via adenylyltransferase. The gene encoding this
      bifunctional enzyme, glnE, was isolated and its function was characterized by
      deletion analysis. Upstream of glnE, a second gene encoding a GSI-type protein in
      C. glutamicum was isolated. This gene, designated glnA2, forms an operon with
      glnE, its transcription is not regulated and neither its deletion or
      overexpression showed any effect. Therefore, the physiological role of glnA2
      remains unclear.

PMID- 11445174
TI  - Purification and characterization of carbaryl hydrolase from Arthrobacter sp.
      RC100.
AB  - A carbaryl hydrolase was purified to homogeneity from Arthrobacter sp. strain
      RC100 by protamine sulfate treatment, ammonium sulfate precipitation, and
      hydrophobic, anion-exchange, and gel filtration chromatographies. The native
      enzyme had a molecular mass of 100 kDa and was composed of two identical subunits
      with molecular masses of 51 kDa. The hydrolase activity was strongly inhibited by
      DIFP, PMSF, Hg(2+) and paraoxon but not by EDTA. The optimum pH and temperature
      for the enzyme activity were 9.0 and 50 degrees C, respectively. The enzyme
      hydrolyzed four N-methylcarbamate insecticides (carbaryl, xylylcarb, metolcarb
      and XMC), but was not able to hydrolyze fenobucarb, propoxur, and isoprocarb.

PMID- 11445175
TI  - Expression of exo-polygalacturonases in Botrytis cinerea.
AB  - The pathogenic fungus, Botrytis cinerea, causing gray mold disease in a variety
      of plant species, secretes at least four polygalacturonases (PGs), cell wall
      degrading enzymes. Among them, we prepared polyclonal antibody against purified
      66-kDa exo-PG in rabbit. Immunoblot analysis revealed that the antibody
      recognized two exo-PGs, 66 kDa and 70 kDa in molecular mass, secreted from B.
      cinerea cultured in the medium containing citrus pectin as a carbon source. By
      immunohistochemical analysis, the expression of exo-PGs was identified in
      cucumber leaves inoculated with spores of B. cinerea. The exo-PGs were observed 9
      h after inoculation, and the amount of exo-PGs increased with time in the leaves.
      The exo-PGs were induced by polygalacturonic acid as well as its monomer,
      galacturonic acid, in vitro. The expression of 66-kDa exo-PG (exo-PG I) increased
      with time of culture, while 70-kDa exo-PG (exo-PG II) was transiently expressed
      soon after the start of culture. Therefore, exo-PGs might play an important role
      in pathogenesis at an early stage of infection as well as in tissue maceration of
      host plant.

PMID- 11445176
TI  - Transcriptional regulation of laccase and cellulase genes during growth and
      fruiting of Lentinula edodes on supplemented sawdust.
AB  - Transcription of laccase and cellulase genes of Lentinula edodes was examined
      during growth and development under different temperature and moisture levels on
      a sawdust-based substrate. RNA was extracted from samples of mycelium and fruit
      bodies at various stages of development and gene expression was determined by
      competitive RT-PCR. The level of laccase transcripts was maximal during the
      mycelial growth stage, and then declined rapidly at the fruiting stage. In
      contrast, the cellulase transcript level peaked at the veil-break stage during
      fruit body development. Gene expressions for laccase and cellulase were triggered
      by microclimatic changes, specifically lower temperature and osmotic pressure.

PMID- 11445180
TI  - The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)
      pyridine (MPEP) blocks fear conditioning in rats.
AB  - Glutamate receptors play an essential role in fear-related learning and memory.
      The present study was designed to assess the role of the group I metabotropic
      glutamate receptor (mGluR) subtype 5 in the acquisition and retrieval of
      conditioned fear in rats. The selective mGluR5 antagonist 2-methyl-6
      (phenylethynyl)-pyridine (MPEP) was applied systemically (0.0, 0.3, 3.0, 30.0
      mg/kg per os) 60 min before the acquisition training and before the expression of
      conditioned fear, respectively, in the fear-potentiated startle paradigm. MPEP
      dose-dependently blocked the acquisition of fear. This effect was not due to
      state-dependent learning. MPEP also prevented the expression of fear at a dose of
      30.0 mg/kg. As a positive control for these effects, we showed that the
      benzodiazepine anxiolytic compound diazepam (1.25 mg/kg intraperitoneally) also
      blocked acquisition and expression of fear potentiated startle. MPEP did not
      affect the baseline startle magnitude, short-term habituation of startle,
      sensitisation of startle by footshocks or prepulse inhibition of startle. These
      data indicate a crucial role for mGluR5 in the regulation of fear conditioning.
      In the highest dose MPEP might exert anxiolytic properties.

PMID- 11445181
TI  - Anti-epileptic activity of group II metabotropic glutamate receptor agonists (--)
      2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268) and (--)-2-thia-4
      aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY389795).
AB  - The selective group II metabotropic glutamate receptor (mGlu(2/3)) agonists (-)-2
      oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268) and (-)-2-thia-4
      aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY389795) have been evaluated as
      anti-epileptic drugs in dilute brown agouti (DBA/2) mice, lethargic (lh/lh) mice,
      genetically epilepsy-prone-9 (GEP) rats and amygdala-kindled rats. Sound-induced
      clonic seizures in DBA/2 mice were transiently inhibited by both agonists
      intracerebroventricularly (i.c.v.), LY379268 ED(50)=0.08 [0.02-0.33]nmol and
      LY389795 ED(50)=0.82 [0.27-3.24]nmol or intraperitoneally (i.p.), LY379268
      ED(50)=2.9 [0.9-9.6]mg/kg and LY389795 ED(50)=3.4 [1.0-11.7]mg/kg. Both mGlu(2/3)
      agonists inhibited seizures induced by the group I mGlu receptor agonist (R,S)
      3,5-dihydroxyphenylglycine (DHPG), where LY379268, i.c.v. ED(50)=0.3 [0.02
      5.0]pmol and LY389795, i.c.v. ED(50)=0.03 [0.05-0.19]nmol. The spike and wave
      discharge (SWD) duration of absence seizures in lh/lh mice was significantly
      reduced by both agonists at 1 and 10nmol (i.c.v.) up to 90min following infusion.
      The electrically induced seizure score and afterdischarge duration of amygdala
      kindled rats was partially inhibited by the agonists 30min after i.p. injection
      of 10mg/kg. The agonists did not inhibit sound-induced seizures in GEP rats (0.1
      1mg/kg, 30min 1h, i.p.), but were proconvulsant following sound stimulus (> or
      =0.1mg/kg). These findings identify a potential role for mGlu(2/3) agonists in
      the amelioration of generalised and partial epileptic seizures.

PMID- 11445182
TI  - Group II mGlu receptor agonists fail to protect against various neurotoxic
      insults induced in murine cortical, striatal and cerebellar granular pure
      neuronal cultures.
AB  - Since group II metabotropic glutamate (mGlu) receptors are a potential target for
      the amelioration of neuronal injury, we evaluated the ability of group II mGlu
      receptor agonists to attenuate toxicity induced by various insults in cortical,
      striatal and cerebellar granular (CGCs) pure neuronal cultures. The three
      cultures, when maintained under serum-free, anti-oxidant rich conditions for up
      to 13 days in vitro (div) were shown by immunocytochemistry to contain a maximum
      of 2-7% glia. At 6, 9 and 13 div a graded pattern of injury to cortical and
      striatal cultures was achieved with either hydrogen peroxide (60-110 microM),
      staurosporine (1 microM), N-methyl-D-aspartate (NMDA, 70 microM), alpha-amino-3
      hydroxy-methylisoxazole-4-propionate (AMPA, 100 microM) or kainate (100 microM)
      over either 4, 24 or 48 h. CGCs were similarly exposed to low K(+) (5.4 mM KCl).
      Cell viability was examined via phase-contrast microscopy and assessed by a 3
      (4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Treatment with
      group II mGlu receptor agonists (1-300 microM), 2R,4R-4-aminopyrrolidine-2,4
      dicarboxylate ((2R,4R)-APDC), (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG
      I), (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) and N
      acetylaspartylglutamate (NAAG) failed to attenuate the toxicity. Pretreatment of
      cultures with the agonists and treatment following acute insult also failed to
      attenuate toxicity. Further investigations demonstrated the presence of second
      messenger activation whereby (2R,4R)-APDC reduced forskolin-stimulated production
      of cAMP in each culture. Thus, despite receptor coupling to intracellular
      signaling cascades, and regardless of culture development, agonist concentration,
      extent and mode of injury, group II mGlu receptor agonists were unable to protect
      against injury induced in cortical, striatal and cerebellar granular pure
      neuronal cultures. This result is in contrast to mixed cultures of neurones and
      glia and implies an important role for glia in the neuroprotective effects of
      group II mGlu receptor agonists.

PMID- 11445183
TI  - Activation of groups I or III metabotropic glutamate receptors inhibits
      excitatory transmission in the rat subthalamic nucleus.
AB  - The subthalamic nucleus (STN) is a key nucleus in the basal ganglia motor circuit
      that provides the major glutamatergic excitatory input to the basal ganglia
      output nuclei. The STN plays an important role in the normal motor function, as
      well as in pathological conditions such as Parkinson's disease. Development of a
      complete understanding of the role of the STN in motor control will require a
      detailed understanding of the mechanisms involved in the regulation of excitatory
      and inhibitory synaptic transmission in this nucleus. Here, we report that
      activation of groups I or III metabotropic glutamate (mGlu) receptors, but not
      group II, causes a depression of excitatory transmission in the STN. In contrast,
      mGlu receptor activation has no effect on the inhibitory transmission in this
      nucleus. Further characterization of the group I mGlu receptor-induced effect on
      EPSCs suggests that this response is mediated by mGlu1 and not mGlu5. Further,
      paired pulse studies suggest that both the mGlu1 receptor and the group III mGlu
      receptor-mediated effects are due to a presynaptic mechanism. If these receptors
      are involved in endogenous synaptic transmission in the STN, these results raise
      the exciting possibility that selective agents targeting mGlu receptors may
      provide a novel approach for the treatment of motor disorders involving the STN.

PMID- 11445184
TI  - Metabotropic glutamate receptor subtypes modulating neurotransmission at parallel
      fibre-Purkinje cell synapses in rat cerebellum.
AB  - The actions of reportedly group-selective metabotropic glutamate (mGlu) receptor
      agonists and antagonists on neurotransmission at parallel fibre-Purkinje cell
      synapses in the rat cerebellum have been characterised using sharp microelectrode
      recording and an in vitro slice preparation. Application of the group I agonist
      (S)-3,5-dihydroxyphenylglycine (DHPG) or the group III selective agonist L(+)-2
      amino-4-phosphonobutyric acid (L-AP4) depressed synaptic transmission in a
      reversible and concentration-dependent manner (EC(50)=18 and 5 microM,
      respectively). The depression produced by DHPG was unrelated to the
      depolarisation observed in some Purkinje cells. The group II agonist (2S,2'R,3'R)
      2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV, 1 microM) had no effect. The
      effects of DHPG were inhibited by the group I-selective antagonist 7
      hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt), but
      not by the group II/III antagonist alpha-methyl-4-phosphonophenylglycine (MPPG).
      The effect of L-AP4 was inhibited by MPPG, but not by the group I/II antagonist
      (S)-alpha-methyl-4-carboxyphenylglycine (MCPG). By themselves, the antagonists
      did not affect the EPSPs, suggesting that neither receptor is activated during
      low frequency neurotransmission. It is concluded that, in addition to the
      excitatory role for group I receptors described previously, both group I and III
      (but not group II) mGlu receptors operate at this synapse to inhibit synaptic
      transmission. The specific receptor subtypes involved are likely to be mGlu1 and
      mGlu4.

PMID- 11445185
TI  - The in vivo relevance of the varied channel-blocking properties of uncompetitive
      NMDA antagonists: tests on spinal neurones.
AB  - The voltage dependence and channel-blocking kinetics of uncompetitive NMDA
      receptor antagonists have been well-described using in vitro techniques, but
      there is little evidence concerning the functional significance of these
      properties in vivo. We have now compared the effects of NMDA antagonists that
      display varied profiles of voltage-dependent block in vitro, on responses of
      spinal neurones in anaesthetised rats. The compounds examined were the
      uncompetitive channel blockers memantine, ketamine and MK-801 and, for
      comparison, an antagonist that acts at the strychnine-insensitive glycine binding
      site (MRZ 2/502). Using frequency of spike discharge as an indicator of somatic
      depolarisation, we have compared the effects of these antagonists on responses
      evoked by iontophoretic NMDA application and on synaptic responses evoked by
      pinch or electrical stimulation (the latter eliciting "wind-up"). The
      effectiveness of the antagonists was directly but variably related to the
      discharge frequency of the test response. The rank order of dependence on firing
      rate matched the rank order of voltage dependence reported in vitro, namely:
      memantine > ketamine > MK-801> or = MRZ 2/502. Doses that reduced responses to
      iontophoretic application of NMDA were less effective at reducing responses to
      pinch, perhaps due to the major non-NMDA component of the synaptic response.
      Memantine preferentially reduced "wind-up" relative to responses to pinch,
      whereas ketamine and MK-801 reduced both types of synaptic responses in parallel.
      This "filtering" by low affinity, voltage-dependent NMDA antagonists such as
      memantine, of non-physiological activity whilst leaving normal synaptic events
      relatively untouched, may contribute to their more favourable clinical profile.

PMID- 11445186
TI  - Dopamine D2 receptor mediated presynaptic inhibition of striatopallidal GABA(A)
      IPSCs in vitro.
AB  - The modulation of GABA release within the globus pallidus (GP) by dopamine was
      studied using whole-cell patch clamp recordings from visually identified
      neurones. In sagittal slices, single shock electrical stimulation in the striatum
      evoked GABA(A) inhibitory postsynaptic currents (IPSCs), which were inhibited by
      dopamine in a dose-dependent manner (0.3-30 microM) with an IC(50) value of 0.7
      microM. The inhibition was accompanied by an increase in paired pulse
      facilitation, indicative of a presynaptic effect. In coronal slices, stimulation
      within the GP adjacent to the recording site evoked GABA(A) IPSCs which were
      relatively unaffected by dopamine indicating the lack of modulation of GABA
      release from terminals of local GP axon collaterals. No consistent changes in
      holding current, membrane potential, firing rate or the frequency of spontaneous
      IPSCs was observed.Tetrodotoxin-resistant miniature (m)IPSCs were recorded in
      chloride-loaded cells. Dopamine (3-30 microM) reduced the frequency of mIPSCs,
      but was without effect on mIPSC amplitude, confirming a presynaptic effect. The
      addition of the "D2 like" agonist quinpirole (3 microM), but not the "D1 like"
      agonist SKF 38393 (10 microM), mimicked these effects. The "D2 like" antagonist
      sulpiride (10 microM), while having no effect alone, blocked the action of
      dopamine. In contrast the dopamine D4 selective antagonist L745, 870 (1 microM)
      or D1 antagonist SCH 23390 (10 microM) were without effect. These results
      indicate that dopamine acts on presynaptic D2 receptors on striatopallidal
      terminals to reduce the release of GABA in the GP. Attenuation of this mechanism
      following the depletion of dopamine may contribute to the changes in GP neuronal
      activity observed in animal models of Parkinson's disease.

PMID- 11445187
TI  - Electrophysiological evidence for postsynaptic 5-HT(1A) receptor control of
      dorsal raphe 5-HT neurones.
AB  - Postsynaptic 5-hydroxytryptamine(1A) (5-HT(1A)) receptors have been proposed to
      participate in the control of dorsal raphe 5-HT neurone activity. To further
      investigate this hypothesis we performed single-unit extracellular recordings in
      anaesthetized rats. Pertussis toxin (2 microg/4 microl/day; 2 days, 24-72 h
      before the experiment) was applied close to the dorsal raphe nucleus to uncouple
      somatodendritic 5-HT(1A) autoreceptors from their effector system. After this
      treatment the spontaneous firing rate was higher (approximately +60% P<0.005)
      than in the vehicle-pretreated group. In addition, intravenous administration of
      8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) inhibited 5 out of 11
      cells of the pertussis toxin-pretreated group (ED(50)=1.65+/-0.94 microg/kg),
      whereas in the vehicle-pretreated group, all tested cells were inhibited
      (ED(50)=1.87+/-0.39 microg/kg). Local administration of 8-OH-DPAT did not affect
      cells (n=12) in pertussis toxin-pretreated rats, even at doses much higher than
      those needed to completely inhibit 5-HT cells in vehicle-pretreated rats
      (ED(50)=3.34+/-0.62 fmol). These results confirm the involvement of distal
      postsynaptic 5-HT(1A) receptors in the control of 5-HT neurone activity in the
      dorsal raphe nucleus. However, this control does not appear to be exerted on all
      5-HT neurones, but rather on a subpopulation of them.

PMID- 11445188
TI  - Inefficient cell-surface expression of hybrid complexes formed by the co-assembly
      of neuronal nicotinic acetylcholine receptor and serotonin receptor subunits.
AB  - Previous studies have demonstrated that relatively low levels of alpha4beta2
      neuronal nicotinic acetylcholine receptors (nAChRs) are expressed on the cell
      surface of transfected mammalian cell lines but that surface expression levels
      can be dramatically up-regulated by co-expression of these subunits with chimeric
      subunits containing the N-terminal portion of the neuronal nAChR alpha4 or beta2
      subunits together with the C-terminal domain of the 5-HT(3A) subunit. Recent work
      has also suggested that the nAChR alpha4 subunit can co-assemble in a
      "promiscuous" manner with the serotonin receptor 5-HT(3A) subunit to form
      functional hybrid receptors. In this study we have examined whether co-assembly
      of either alpha4 or beta2 with 5-HT(3A) itself (rather than with the alpha4/5
      HT(3A) or beta2/5-HT(3A) subunit chimeras) can also facilitate cell surface
      expression of alpha4 and beta2 subunits in transfected mammalian cells. Evidence
      has been obtained by immunoprecipitation, cell-surface antibody binding and
      radioligand binding which indicates that the 5-HT(3A) can co-assemble with both
      the alpha4 and beta2 nAChR subunits. We conclude, however, that co-assembly of 5
      HT(3A) with either alpha4 or beta2 does not result in efficient cell surface
      expression of the nAChR subunits and that co-assembled hybrid (nAChR subunit + 5
      HT(3)R subunit) receptor complexes are largely retained within the cell.

PMID- 11445189
TI  - Pharmacological assessment of the role of the glycine transporter GlyT-1 in
      mediating high-affinity glycine uptake by rat cerebral cortex and cerebellum
      synaptosomes.
AB  - Two distinct types of glycine transporter, GlyT-1 and GlyT-2, have been
      characterised. GlyT-1 and GlyT-2 are known to be differentially expressed amongst
      CNS areas, but direct functional evidence for their relative contributions to
      high-affinity glycine uptake by brain tissues is lacking. In the present study,
      we have used the selective GlyT-1 inhibitor N[3-(4"-fluorophenyl)-3-(4"
      phenylphenoxy)propyl]sarcosine (NFPS) to investigate the role of GlyT-1 in
      mediating glycine uptake. HEK293 cells expressing human GlyT-1c or GlyT-2 showed
      high levels of Na(+)-dependent glycine uptake, with K(m) values of 117+/-13 and
      200+/-22 microM, respectively. NFPS potently inhibited uptake in GlyT-1c cells
      (IC(50) value 0.22+/-0.03 microM), being around 500-fold more potent than glycine
      or sarcosine, but had no effect on uptake in GlyT-2 cells (IC(50) >10 microM).
      Efflux of pre-loaded [3H]-glycine from GlyT-1c cells was increased by glycine or
      sarcosine, whereas NFPS had no effect on its own but blocked the effects of
      glycine or sarcosine. These results confirm that NFPS is a potent, selective and
      non-transportable GlyT-1 inhibitor. Rat cortex and cerebellum synaptosomes also
      showed a high-affinity Na(+)-dependent component of glycine uptake, with
      affinities similar to those observed for uptake in GlyT-1c or GlyT-2 cells. In
      cortex synaptosomes, NFPS and sarcosine produced the same maximal inhibition of
      uptake as glycine itself. However, in cerebellum synaptosomes, the maximal
      inhibition produced by NFPS and sarcosine was only half that produced by glycine.
      In both tissues NFPS was around 1000-fold more potent than glycine or sarcosine.
      Overall, our findings indicate that high-affinity glycine uptake in cerebral
      cortex occurs predominantly via GlyT-1. However, in cerebellum, only a part of
      the high-affinity uptake is mediated by GlyT-1, with the remaining NFPS
      insensitive component most likely mediated by GlyT-2.

PMID- 11445190
TI  - Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent
      neurological function.
AB  - Identification of synthetic agonists and antagonists at orphan receptors
      represents an important step for understanding their physiological function and
      therapeutic potential. Accordingly, we have recently described a non-peptide
      agonist at the opioid receptor like (ORL1) receptor (1S,3aS)-8-(2,3,3a,4,5,6
      hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro64
      6198; Jenck et al., PNAS 94 (2000) 4938; Wichmann et al., Eur. J. Med. Chem. 35
      (2000) 839). We have investigated the effects of this compound in various tests
      of rodent neurological function, utilising ORL1 knockout mice to examine the
      pharmacological specificity of Ro64-6198. In male C57BL/6J mice, effects on
      balance and motor co-ordination were detected following low doses (0.3-1mg/kg IP)
      of Ro64-6198. At higher doses (1-3mg/kg IP), effects on swim behaviour and
      hypothermia was observed. At 10mg/kg, each effect became more profound and a
      severe neurological disturbance appeared, including loss of righting reflex.
      These effects of Ro64-6198 (10mg/kg IP) were absent in ORL1 receptor knockout
      mice. In male, hooded Lister rats, Ro64-6198 (6-10mg/kg IP), produced some
      disturbance of neurological function, including hypoactivity, rotarod
      performance, grip strength and mild hypothermia. An impairment of food responding
      under a variable interval (VI) 20s schedule of reinforcement was noted at 3mg/kg.
      These results confirm Ro64-6198 to be a highly selective pharmacological tool to
      investigate ORL1 receptor function in vivo and, furthermore, that activation of
      this receptor is accompanied by a variety of effects on neurological function.

PMID- 11445191
TI  - Chronic infusion of nicotine can increase operant self-administration of alcohol.
AB  - Effects of nicotine, administered by continuous infusion via osmotic minipumps,
      were studied on the operant self-administration of alcohol by rats, using a
      variable interval (15 s) schedule, and measuring the acquisition, maintenance,
      extinction and reinstatement of responding for alcohol. Doses of nicotine of
      0.25, 1.25 and 7.5 mg/kg/24 h had no significant effects on the maintenance of
      responding for alcohol, but 5 mg/kg/24 h nicotine resulted in a significant
      increase in responding on the lever delivering the reward when water was
      substituted for the alcohol, indicating delayed extinction of responding. During
      infusion of 2.5 mg/kg/24 h nicotine, responding was significantly greater over
      the "sucrose-fading" training sessions, during acquisition of responding, when
      mixtures of alcohol and sucrose were provided as reward. When minipumps infusing
      2.5 mg/kg/24 h nicotine were implanted after the alcohol responding had been
      acquired, the responding for alcohol increase during the first week of nicotine
      infusion, but corresponding nicotine infusion doses of 0.25, 1.25 and 7.5 had no
      significant effects. The results indicate that nicotine can increase operant
      responding for alcohol and this is crucially dependent on the dose of nicotine
      and the time of testing. The results have implications for the frequently
      encountered dependence on the combination of alcohol and nicotine.

PMID- 11445192
TI  - Chronic treatment with Delta(9)-tetrahydrocannabinol enhances the locomotor
      response to amphetamine and heroin. Implications for vulnerability to drug
      addiction.
AB  - Cannabis sativa preparations are some of the most widely used illicit
      recreational drugs. In addition to their direct addictive potential, cannabinoids
      may influence the sensitivity to other drugs. The aim of the present study was to
      determine if a cross-sensitization between Delta(9)-tetrahydrocannabinol
      (Delta(9)-THC) and other drugs (amphetamine and heroin) could be demonstrated. We
      examined the effects of a chronic treatment with Delta(9)-THC (0.6, 3 and
      15mg/kg, ip) on the locomotor response to amphetamine (1mg/kg, ip) and heroin
      (1mg/kg, ip). Chronic treatment with Delta(9)-THC resulted in tolerance to the
      initial hypothermic and anorexic effects. Pre-treatment with Delta(9)-THC
      increased the locomotor responses to amphetamine and heroin. This cross
      sensitization was time-dependent as it was observed three days after the last
      injection of Delta(9)-THC for amphetamine, and a relatively long time after the
      end of chronic treatment (41 days) for heroin. Moreover, the enhanced response to
      amphetamine or heroin was noted in some individuals only: the high-responder rats
      (HR). These animals have previously been shown to be vulnerable to drug taking
      behaviors. It is hypothesised that repeated use of Cannabis derivates may
      facilitate progression to the consumption of other illicit drugs in vulnerable
      individuals.

PMID- 11445193
TI  - Intra-amygdala injection of the substance P [NK(1) receptor] antagonist L-760735
      inhibits neonatal vocalisations in guinea-pigs.
AB  - The involvement of the basolateral amygdala in mediating the inhibition of
      neonatal vocalisation by substance P (NK(1) receptor) antagonists was examined.
      These studies determined whether the time course for separation-induced
      vocalisations in guinea-pig pups coincided with NK(1) receptor internalisation (a
      marker of substance P release) in the amygdala, and whether vocalisations could
      be blocked by focal injection of the NK(1) receptor antagonist L-760735 into this
      brain region. The peak period for neonatal vocalisations occurred 5-10 min
      following maternal separation. This coincided with the peak increase in the
      number of cells in the basolateral amygdala exhibiting NK(1) receptor
      endocytosis, consistent with the proposal that substance P is released in the
      amygdala as a result of isolation stress. Focal injection of L-760735 (15 nmol
      per side) but not L-770765 (an analogue of L-760735 which has low NK(1) receptor
      affinity) into the basolateral amygdala attenuated separation-induced
      vocalisations. In contrast, injection of L-760735 (15 nmol per side) into the
      dorsal ventricular nucleus of the thalamus, a region with relatively low density
      of NK(1) receptors, had no effect on neonatal vocalisations. These findings are
      consistent with other evidence that the amygdala is one possible site of action
      for the inhibition of neonatal vocalisations by substance P antagonists.

PMID- 11445194
TI  - Neuropharmacological profile of a selective sigma ligand, igmesine: a potential
      antidepressant.
AB  - Igmesine is a selective sigma (sigma(1)) ligand that was reported to exert
      antidepressant action through an unknown mechanism of action. A number of
      neurochemical measures were taken in this study in efforts to understand its mode
      of action. Following 21-day drug treatments, the actions of igmesine on a number
      of neurochemical measures were investigated. Data obtained showed significant
      decreases in the densities of beta-adrenergic but not 5-HT(1A), sigma(1) and
      GABA(B) receptors in fluoxetine (18%), desipramine (DMI, 32%) and igmesine (20%)
      treated groups when compared with control. Tyrosine hydroxylase (TH) activity was
      significantly (30-32%) reduced in all treated groups. Further, fluoxetine and DMI
      excluding the igmesine-treated groups showed 85 and 40% reductions in serotonin
      (5-HT) and noradrenaline (NE) neuronal uptake, respectively. Following acute
      treatment, igmesine lacked activity for monoamine oxidase (MAO) A or B (IC(50)>10
      microM). In in vivo studies, at behaviorally active doses, igmesine showed weak
      effects on the NE uptake but lacked activity in altering 5-HT and DA synthesis or
      antagonizing selective drug-induced depletion of monoamine neuronal uptake. N
      methyl-D-aspartate (NMDA)-induced increases in cGMP was blocked by igmesine
      indicating that igmesine may interfere with the NMDA receptor/nitric oxide
      synthase/cGMP pathway. Although it appears that part of the pharmacological
      actions of igmesine is mediated by the monoaminergic system, there is still need
      to explore other possible mechanisms of antidepressant action.

PMID- 11445196
TI  - Simulation of acute spinal cord injury: effects on respiration.
AB  - The respiratory effects of acute spinal injury and paralysis are difficult to
      study. Urgent medical needs of human spinal cord injury victims usually preclude
      study, while induction of spinal cord lesions in awake animals is not feasible
      ethically. We utilized controlled, segmental infusion of epidural anesthetic in
      awake, highly trained, implanted canines to reversibly simulate the effects of
      thoracic and cervical (paraplegic and quadriplegic) spinal cord injury. We
      studied six animals, an average of 29 days after implantation with electromyogram
      and sonomicrometry transducers in transversus abdominis, external intercostal,
      parasternal intercostal and costal diaphragm muscles. Anesthetic was infused
      through an epidural catheter inserted percutaneously, under fluoroscopic
      guidance. Asymmetrical motor blockade was prevented using repositioning during
      epidural infusions. By sequential infusion we were able to induce three distinct,
      functional levels of spinal paralysis showing cumulative paralysis of abdominal,
      external intercostal, and parasternal intercostal muscles. Paralysis of the
      abdomen and chest wall, sparing only the diaphragm, showed unexpected bradypnea
      and failure to maintain minute ventilation.

PMID- 11445197
TI  - Airway ammonia negates the normal ventilatory response to airway CO(2) in garter
      snakes.
AB  - Earlier studies from this lab showed that unidirectionally ventilated snakes,
      maintained on high airway [CO(2)], breathe slowly with a large tidal volume. If
      airway [CO(2)] is abruptly reduced during inspiration, inspiratory duration (TI)
      and tidal volume increase. On the other hand, in an animal normally receiving
      fresh air (no CO(2) in the inspired air) on each inspiration, if fresh air is
      withheld for one breath, TI and tidal volume decrease. To test the effect of
      producing an alkaline environment in the presence of CO(2) during these two
      maneuvers, six unidirectionally ventilated snakes weighing 32+/-16 g were
      maintained on 4% CO(2) in air flowing at 300 ml/min even during inspiration.
      NH(3) (4%) was introduced into the lung during one inspiration. During that
      breath, TI increased significantly, as if CO(2) had been removed from the lung.
      In another study, six different snakes weighing 21+/-6 g received fresh air at
      each inspiration. At the end of inspiration [CO(2)] was again raised to 4%.
      However, for one breath, [CO(2)] was maintained high during inspiration and
      airway NH(3) (3--4%) was simultaneously introduced into the airstream. During
      this breath, TI was expected to decrease, owing to the elevated [CO(2)]; however,
      there was no significant difference in the TI of the test breath compared with
      the previous breath, indicating that ammonia interfered with the expected CO(2)
      response. This study suggests that pH (probably intracellular) rather than
      P(CO(2)) produces this ventilatory reflex.

PMID- 11445198
TI  - Genioglossal inspiratory activation: central respiratory vs mechanoreceptive
      influences.
AB  - Upper airway dilator muscles are phasically activated during respiration. We
      assessed the interaction between central respiratory drive and local
      (mechanoreceptive) influences upon genioglossal (GG) activity throughout
      inspiration. GG(EMG) and airway mechanics were measured in 16 awake subjects
      during baseline spontaneous breathing, increased central respiratory drive
      (inspiratory resistive loading; IRL), and decreased respiratory drive (hypocapnic
      negative pressure ventilation), both prior to and following dense upper airway
      topical anesthesia. Negative epiglottic pressure (P(epi)) was significantly
      correlated with GG(EMG) across inspiration (i.e. within breaths). Both passive
      ventilation and IRL led to significant decreases in the sensitivity of the
      relationship between GG(EMG) and P(epi) (slope GG(EMG) vs P(epi)), but yielded no
      change in the relationship (correlation) between GG(EMG) and P(epi). During
      negative pressure ventilation, pharyngeal resistance increased modestly, but
      significantly. Anesthesia in all conditions led to decrements in phasic GG(EMG),
      increases in pharyngeal resistance, and decrease in the relationship between
      P(epi) and GG(EMG). We conclude that both central output to the GG and local
      reflex mediated activation are important in maintaining upper airway patency.

PMID- 11445199
TI  - Effect of series of resistance levels on flow limitation in mechanically
      ventilated COPD patients.
AB  - In severe chronic obstructive pulmonary disease (COPD) lung emptying is disturbed
      by airways compression and expiratory flow limitation. Application of an external
      resistance has been suggested to counteract airways compression and improve lung
      emptying. We studied the effect of various resistance levels on lung emptying in
      mechanically ventilated COPD patients. In 18 patients an adjustable resistor was
      applied. The effect on airways compression was assessed by iso-volume pressure-
      flow curves (IVPF) and by interrupter measurements. Respiratory mechanics during
      unimpeded expirations were correlated to the results obtained with the
      resistances. The resistances caused an increase in iso-volume flow at the IVPF
      curves in six patients, indicating that airways compression was counteracted.
      Interrupter measurements showed that overshoots in flow (as measure of flow
      limitation) were significantly reduced by the resistor. These effects could be
      predicted on basis of respiratory mechanics during unimpeded expiration. In
      conclusion, mechanically ventilated COPD patients can be identified in whom
      application of external resistances counteracts airways compression and reduces
      flow limitation.

PMID- 11445200
TI  - Mild hypoxia causes severe pulmonary hypertension in fawn-hooded but not in
      Tester Moriyama rats.
AB  - The purpose of this study was to test whether the Tester Moriyama rat (TMR), a
      strain that has a serotonin platelet storage-pool deficiency similar to that of
      the fawn-hooded rat (FHR), develops severe pulmonary hypertension (PH) upon
      exposure to mild hypoxia. We compared hemodynamic parameters in catheterized 10
      week-old FHR, TMR, and control Wistar rats that had been raised from birth to 10
      weeks of age under normoxia (PI(O(2)) approximately 150 mmHg) or mild hypobaric
      hypoxia (PI(O(2)) approximately 120 mmHg). Mean pulmonary artery pressure and
      right ventricle to left ventricle plus septum weight ratio were much higher in
      the mildly hypoxic FHR compared with the normoxic FHR. These parameters were only
      increased slightly by exposure to mild hypoxia in the TMR and Wistar rats. Mild
      hypoxia did not affect mean systemic artery pressure in any of the rat strains.
      Exposure of FHR to mild hypoxia from 4 to 10 weeks of age did not lead to
      development of PH. Endothelin-1 (ET-1) mRNA and peptide levels were increased in
      the hypertensive lungs of mildly hypoxic FHR compared with the normotensive lungs
      of normoxic FHR, and of normoxic and mildly hypoxic TMR and Wistar rats. These
      results suggest that mild hypoxia causes severe PH and upregulation of lung ET-1
      expression in neonatal FHR but not in neonatal TMR, and that the period from
      birth to 4 weeks of age is critical for the development of the severe PH in the
      FHR. A serotonin PSPD does not predispose rats to hypoxia-induced PH.

PMID- 11445201
TI  - Prenatal exposure to nicotine impairs protective responses of rat pups to hypoxia
      in an age-dependent manner.
AB  - Experiments were carried out on rat pups to investigate the interaction between
      prenatal exposure to nicotine and postnatal age on protective responses that
      promote survival during exposure to hypoxia. From days 6 or 7 of gestation,
      pregnant rats received either nicotine (approximately 6 mg of nicotine
      tartrate/kg of body weight per day) or vehicle continuously via a 28-day osmotic
      minipump. On postnatal days 1--2, 5--6 and 10--11, the pups were exposed either
      to a single period of hypoxia produced by breathing an anoxic gas mixture (97%
      N(2) and 3% CO(2)) and their time to last gasp determined, or they were exposed
      repeatedly to hypoxia and their ability to autoresuscitate from primary apnea
      determined. Prenatal exposure to nicotine decreased the time to last gasp, but
      only in the 1--2-day-old animals. The total number of gasps was, however,
      increased in this age group due to the effect of nicotine on the gasping pattern.
      Furthermore, prenatal exposure to nicotine decreased the number of successful
      autoresuscitations and influenced the cardiorespiratory events preceding death in
      the 1--2- and 5--6-day-old pups but not in the 10--11-day-old pups. Thus, our
      experiments show that prenatal exposure to nicotine impairs protective responses
      of rat pups that may sustain life during exposure to hypoxia in an age-dependent
      manner.

PMID- 11445202
TI  - Exact morphometric modeling of rat lungs for predicting mechanical impedance.
AB  - We have developed a computational approach that allows for one-to-one mapping of
      the airway anatomy when predicting the overall lung mechanical properties and
      their response to explicit constriction patterns imposed on the airway tree.
      Specifically, we have exploited the database from Raabe et al. (LF-53
      Albuquerque, NM: Lovelace foundation for radical Education and Research), to
      build the first anatomically based computational model of the rat. The model was
      then used to predict the response to homogeneous and heterogeneous peripheral
      airway constriction. Unlike in humans, the inherent asymmetry in the airway tree
      of rats is predicted to be a dominant contributor to the frequency dependence of
      lung resistance and elastance even if the constriction is imposed homogeneously.
      A similar approach would, in principal, be applicable for humans, but the Raabe
      data is not sufficiently complete to permit this.

PMID- 11445203
TI  - "No-bottle" vs "multi-bottle" dentin adhesives--a microtensile bond strength and
      morphological study.
AB  - PURPOSE: To compare the adhesive capability of the new adhesive Prompt L-Pop
      (ESPE) with that of two total-etch adhesive systems-EBS Multi (ESPE) and
      Prime&Bond NT (Dentsply). METHODS: Extracted human molars were bonded and
      prepared for microtensile dentin bond strength (microTBS) testing using Prompt L
      Pop, EBS Multi, and Prime&Bond NT combined with Pertac II (composite) or Hytac
      Aplitip (compomer). Prompt L-Pop was applied using five different protocols: (1)
      as an "all-in-one" self-conditioning adhesive, as per manufacturer's instructions
      (LP); (2) as a self-etching primer combined with a separate bonding resin
      (LP/self-etch 2-step); (3) as a classical primer used upon etching dentin with
      phosphoric acid, followed by a bonding resin (LP/total-etch 3-step); (4) as a
      multi-application "all-in-one" self-conditioning adhesive (LP/multi-coat) to
      leave a visibly glossy dentin surface; and (5) as a filled adhesive, upon adding
      quartz fillers to its composition (LP/filled). After 24h of storage in water at
      37 degrees C the microTBS were measured in an Instron machine. Corresponding
      interfaces of the same specimens were micromorphologically analyzed using SEM and
      TEM. RESULTS: When used with a composite resin, LP/filled and LP/multi-coat
      resulted in significantly higher microTBS than LP. The addition of an extra
      adhesive bonding resin (LP/self-etch 2-step) had no effect on bond strength. The
      use of Prompt L-Pop as a primer of a fourth-generation adhesive (LP/total-etch 3
      step) replacing the EBS Multi primer, resulted in lower bond strengths than those
      of the original EBS Multi. LP/multi-coat showed similar microTBS to Prime&Bond NT
      (P&BNT). When used with a compomer, LP exhibited higher bond strengths than when
      used with the resin composite and was as effective as the experimental groups
      LP/filled and LP/multi-coat and the control group P&BNT. The SEM evaluation
      showed an inconsistent hybrid layer for the LP specimens, whereas in both the
      LP/filled and LP/multi-coat specimens a hybrid layer was clearly evident. Under
      the TEM all groups displayed dentin hybridization with dissolved smear plugs in
      the specimens that had been conditioned with Prompt L-Pop without a separate
      etching step. In many tubules of specimens conditioned with LP (as per
      manufacturer's instructions), fillers of the resin composite were present within
      the dentinal tubules. CONCLUSIONS: When combined with a resin composite, Prompt L
      Pop resulted in statistically lower bond strengths when applied in one layer than
      when applied in multiple layers. Prompt L-Pop also resulted in higher bond
      strengths when used with a polyacid-modified composite resin than with a
      composite resin. When applied in multiple coats, Prompt L-Pop results in bond
      strengths that are not statistically different from those of Prime&Bond NT, a
      total-etch adhesive.

PMID- 11445204
TI  - The application of magnetic resonance microimaging to the visible light curing of
      dental resins. 3. Stray-field nuclear magnetic resonance imaging (STRAFI).
AB  - OBJECTIVE: To investigate the application of stray-field nuclear magnetic
      resonance imaging (STRAFI) to the visible light curing of dental restorative
      materials. STRAFI can overcome peak broadening associated with the conventional
      magnetic resonance microimaging (MRM) of glassy polymers, and has the potential
      to image dental restorative resins at both low and high degrees of conversion.
      METHODS: Cylindrical composite specimens were light-cured from one end to produce
      some that were fully cured throughout their length and others that were fully
      cured at one end and uncured at the other. A one-dimensional probe was used to
      measure the magnetisation in 40 microm thick slices at 100 microm intervals along
      the length of the specimen. A quadrature pulse sequence was applied and the
      magnetisation decay recorded in a train of eight echoes. RESULTS: A value for
      T(2) could be obtained only for the polymer (59+/-16 microms), therefore the
      echoes were summed to give an approximate indication of the degree of conversion.
      The echo sum for the monomer was significantly higher than that for the polymer.
      Differences in composite shade and cure time produced changes in the cure
      profiles. SIGNIFICANCE: STRAFI produced measurements for both monomer and polymer
      in all stages of conversion that allowed cure profiles to be produced. Summing
      the decay echoes produced a qualitative measure of the condition of the material
      in the selected slice. The same data can be used to calculate T(2), a
      quantitative parameter. This first investigation has demonstrated that STRAFI is
      well suited to polymerisation studies.

PMID- 11445205
TI  - Effect of heat treatment on mechanical properties of age-hardenable gold alloy at
      intraoral temperature.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of various heat
      treatments on the mechanical properties of gold alloys capable of age-hardening
      at intraoral temperature. METHODS: Dumbbell-shaped patterns (ISO 6871) were cast
      with three gold alloys (Sofard; NC Type-IV; Aurum Cast, NihombashiTokuriki Co.).
      The Sofard alloy is age-hardenable at intraoral temperature. The castings
      underwent various heat treatments [as-cast (AC); solution treatment (ST); high
      temperature aging (HA); intraoral aging (IA)]. After these heat treatments,
      ultimate tensile strength (UTS), 0.2% offset yield strength (YS), and elongation
      (EL) were measured at a strain rate of 1.7x10(-4)/s. Fracture surfaces of the
      specimens after tensile testing were observed using SEM. Vickers hardness was
      also measured after heat treating. RESULTS: After IA, the hardness values of the
      Sofard alloy increased and reached values similar to the hardness of the Sofard
      specimens aged at high temperature (HA). The hardness values of the NC Type-IV
      and Aurum Cast specimens slightly increased after IA, but did not reach the
      values of the specimens after HA. All the Sofard, NC Type-IV and Aurum Cast
      specimens showed significantly (P<0.05) greater hardness values after HA,
      compared with the values after any other heat treatments (AC, ST and IA). The UTS
      and YS of the specimens indicated a tendency similar to the results obtained for
      hardness. The Sofard specimens with ST showed the greatest elongation compared to
      the corresponding NC Type-IV and Aurum Cast specimens. However, the elongation of
      the Sofard specimens was abruptly reduced after intraoral aging. CONCLUSION:
      Intraoral aging significantly improved the mechanical properties and hardness of
      the Sofard alloy.

PMID- 11445206
TI  - Water sorption and mechanical behaviour of cosmetic direct restorative materials
      in artificial saliva.
AB  - OBJECTIVES: To evaluate the water sorption and mechanical behaviour of a compomer
      in comparison with those of its nominal forerunners, a filled resin restorative
      material and a conventional glass ionomer cement. METHOD: Compomer (Dyract AP) (D
      AP), filled resin (SureFil) (SF), and glass ionomer (ChemFlex) (CF) (all
      Dentsply, Addlestone, UK) restorative materials were tested. Forty bar specimens
      (26x1.5x1.0mm(3)) of each material were prepared according to the manufacturer's
      instructions and randomly distributed into eight groups: dry air (22% RH),
      saturated water vapour (WV) (100% RH), and five in artificial saliva (AS) at pH6,
      all at 37 degrees C, as well as untreated control (UC) (23 degrees C, 50% RH).
      Water sorption was assessed gravimetrically; flexural strength and elastic
      modulus were determined in three-point bend. The control group was tested at 24h;
      AS groups were separately tested after 0.5, 1, 3, 6 and 9 months; the other two
      at 9 months. RESULTS: Mass gain for SF, D-AP and CF in AS was up to 0.17%, 1.2%
      and 7.0%, respectively. CF showed a marked decrease of strength in AS compared
      with other groups, followed by a gradual slight rise to a peak at 3 months.
      Unlike SF and CF, whose flexural strength remained relatively stable, that of D
      AP showed a sharp decline from the 1 month peak (P=6x10(-7)) after 6 months in
      AS. D-AP also showed a slight decline in flexural modulus from a peak, that of SF
      was quite stable, while CF showed no peak. The values of flexural strength for
      both CF and D-AP at 9 months were significantly lower in AS than WV, but SF
      showed no such difference. SIGNIFICANCE: Materials intended for service in the
      mouth must be stored in a realistic medium if the results of testing are to be
      interpretable. Dyract AP, a compomer, does not seem suitable for application in
      stress bearing areas as is currently recommended by its manufacturer. The rapid
      decline in flexural strength after 1 month of exposure to AS and its progressive
      fall in flexural modulus suggest a progressive deterioration of the material and
      this necessitates re-examination of the chemistry of compomers, if the behaviour
      is typical of the class.

PMID- 11445207
TI  - Effect of enamel pretreatments on bond strength of compomer.
AB  - OBJECTIVES: The objective of this study was to evaluate the effect of various
      enamel surface treatments on the bond strength of a compomer to enamel. METHODS:
      Ground bovine enamel specimens were divided into four groups. A compomer (F2000,
      3M) was bonded to the specimens using different enamel surface treatments. Two
      groups examined the effect of application of the F2000 self-etching
      primer/adhesive (3M) with respect to static or dynamic priming. A third examined
      use of the primer/adhesive after phosphoric acid etching, and the fourth
      (control) group provided bond strength of the compomer to phosphoric acid etched
      enamel with a resin bonding system (Single Bond, 3M). Shear bond strengths for
      the specimens were measured after 24h storage in water at 37 degrees C. Effects
      of the various surface treatments on enamel were examined by SEM. RESULTS:
      Significant differences in bond strength of compomer to enamel were found that
      were related to the various surface pretreatments. Dynamic priming resulted in
      higher enamel bond strengths than static priming, and the best bond strengths
      were obtained when the enamel was etched with phosphoric acid. SEM analysis
      showed that depth of etch and resin penetration was also directly related to the
      bond strengths measured. SIGNIFICANCE: Bond strength of compomer to enamel is
      significantly affected by the method of pretreatment of the enamel.

PMID- 11445208
TI  - Elemental release from dental casting alloys into biological media with and
      without protein.
AB  - OBJECTIVE: The objective of this study was to determine the role of proteins in
      affecting elemental release from a variety of clinically available dental casting
      alloys. An important role for proteins was suspected based on previous reports
      about the corrosion of stainless steel and the cytotoxicity of alloys after
      exposure to a saline-protein solution. METHODS: Clinically available alloys with
      compositions ranging from 0 to 94at.% noble elements were exposed for 1 week to
      either saline, saline with 3% bovine serum albumin (BSA), or complete cell
      culture medium with 3% serum. Atomic absorption spectrophotometry was used to
      measure the release of elements from the alloys. Elemental release was normalized
      for the exposed surface area of the alloys. RESULTS: In general, more elemental
      release occurred into the saline-BSA solution compared to saline alone for all
      released elements (Ag, Cu, Pd, and Zn) except for Ni. Ni release from the NiCr
      alloy was lower in the presence of BSA. Each element responded somewhat
      differently with Pd being the least predictable in its behavior. Elemental
      release was less in the cell-culture medium than in the saline-BSA solution for
      most elements. For alloys which released multiple elements, all elements
      responded similarly but not identically to the presence of protein. A high
      elemental release during exposure to the saline-BSA solution correlated with a
      low alloy cytotoxicity post-exposure to the saline-BSA. SIGNIFICANCE: This study
      demonstrates the importance of defining exactly the composition of biological
      solutions used to assess in vitro corrosion and biocompatibility of dental
      casting alloys. Other molecules in addition to proteins appeared to be critical
      to the corrosion of these alloys in vitro.

PMID- 11445209
TI  - Suitability of a shear punch test for dental restorative materials.
AB  - OBJECTIVE: The aim of the study was to evaluate the suitability of a shear punch
      test for determining the mechanical properties of dental restorative materials.
      The method was evaluated by measuring and comparing the shear punch strength of
      seven different restorative materials, that is amalgam, composite resin,
      compomer, composite containing pre-reacted glass ionomer filler, resin modified
      glass ionomer, glass ionomer and polycarboxylate cement. METHOD: The effects of
      specimen restraining conditions, specimen thickness and test speed on the shear
      punch strength were evaluated using polycarboxylate cement and two different
      equipment set-ups. Using the preferred testing regime as determined in the
      preliminary experiments, the shear punch strength of seven different materials
      were measured and compared. Twenty disc specimens, 0.5mm thick and 10mm diameter,
      were prepared for each material, restrained within the test equipment and tested
      at a speed of 1.0mm/min. RESULTS: The shear punch strength increased as the
      torque used for restraining a specimen was increased. There was no difference in
      shear punch strength for specimens of different thickness. The greatest shear
      punch strength was obtained at the test speed of 1.0mm/min. The shear punch
      strength values decreased in the order composite>composite containing pre-reacted
      glass ionomer filler>amalgam>compomer>resin-modified glass ionomer>glass
      ionomer>polycarboxylate. A difference in the shear punch strength for seven
      different kinds of restorative materials clearly emerged. Specimen fracture
      occurred by circumferential cracking for the shear-punch test. However, for some
      glass ionomer and amalgam specimens radial cracking was also observed.
      SIGNIFICANCE: This study suggests that the simple test described is suitable for
      standardization purposes.

PMID- 11445210
TI  - Efficacy of different adhesive techniques on bonding to root canal walls: an SEM
      investigation.
AB  - OBJECTIVES: Recently, several adhesives have been proposed for bonding fiber
      posts into root canals. The aim of this study was to evaluate the influence of
      four adhesive procedures in resin tag, adhesive lateral branch and resin dentin
      interdiffusion zone (RDIZ) formation when used to bond fiber posts. METHOD: Forty
      anterior teeth, extracted for periodontal reasons and endodontically treated,
      were selected for this study. The samples were randomly divided into four groups
      of ten samples each. Group 1: One Step applied with the small brush provided by
      the manufacturer and LC (Light-cured before resin cement application)+Dual Link
      resin cement; Group 2: One Step applied with a thin microbrush LC+Dual Link resin
      cement; Group 3: One Step applied with a small brush (Not light-cured)+Dual Link
      resin cement; Group 4: All Bond 2+C & B resin cement (as control). In Group 2 and
      4 the adhesive system and resin cement were used strictly following
      manufacturers' instructions. In Group 1, One Step was applied using a thin
      microbrush, while in the other groups by a small brush. In Group 1 and 2 the
      priming-adhesive solution of the "one-bottle" system was light-cured before
      placing the resin cement and the post, whereas in Group 3 the adhesive/resin
      cement combination was light cured through the translucent post. Forty
      translucent posts (RTD, France) were used. A week later, the root samples were
      processed for SEM observations. RESULTS: Microscopic examination of restored
      interfaces of Group 1 showed a higher % (P<0.05) of RDIZ than those found in
      samples of Group 2, 3 and 4. In Group 2, 3 and 4 samples RDIZ morphology was well
      detectable and uniform in the first two thirds of root canals while in the apical
      third the RDIZ was not uniformly present. No statistically significant
      differences were found among the groups coronally, whereas apical and middle
      thirds of Group 1 showed significantly more resin tags than the other three
      Groups. In the apical third of Group 2, 3 and 4 samples, the resin tags showed a
      less uniform morphology and a shorter length than those found in the other two
      thirds. SIGNIFICANCE: A microbrush might clinically be used for bonding fiber
      posts into the root canal. When a microbrush was used, the bonding mechanism
      created between root canal dentin and bonding system was uniform along canal
      walls and more predictable.

PMID- 11445211
TI  - Aggressiveness of contemporary self-etching adhesives. Part II: etching effects
      on unground enamel.
AB  - OBJECTIVES: The aggressiveness of three self-etching adhesives on unground enamel
      was investigated. Ultrastructural features and microtensile bond strength were
      examined, first using these adhesives as both the etching and resin-infiltration
      components, and then examining their etching efficacy alone through substitution
      of the proprietary resins with the same control resins. METHODS: For SEM
      examination, buccal, mid-coronal, unground enamel from human extracted bicuspids
      were etched with either Clearfil Mega Bond (Kuraray), Non-Rinse Conditioner (NRC;
      Dentsply DeTrey) or Prompt L-Pop (ESPE). Those in the control group were etched
      with 32% phosphoric acid (Bisco) for 15s. They were all rinsed off prior to
      examination of the etching efficacy. For TEM examination, the self-etching
      adhesives were used as recommended. Unground enamel treated with NRC were further
      bonded using Prime&Bond NT (Dentsply), while those in the etched, control group
      were bonded using All-Bond 2 (Bisco). Completely demineralized, resin replicas
      were embedded in epoxy resin for examination of the extent of resin infiltration.
      For microtensile bond strength evaluation, specimens were first etched and bonded
      using the self-etching adhesives. A second group of specimens were etched with
      the self-etching adhesives, rinsed but bonded using a control adhesive. Following
      restoration with Z100 (3M Dental Products), they were sectioned into beams of
      uniform cross-sectional areas and stressed to failure. RESULTS: Etching patterns
      of aprismatic enamel, as revealed by SEM, and the subsurface hybrid layer
      morphology, as revealed by TEM, varied according to the aggressiveness of the
      self-etching adhesives. Clearfil Mega Bond exhibited the mildest etching
      patterns, while Prompt L-Pop produced an etching effect that approached that of
      the total-etch control group. Microtensile bond strength of the three
      experimental groups were all significantly lower than the control group, but not
      different from one another. When the self-etching adhesives were replaced with
      the control adhesive after etching, bond strengths of NRC/Prime&Bond NT and
      Prompt L-Pop were not significantly different from that of the control group, but
      were significantly higher than that of Clearfil Mega Bond. SIGNIFICANCE: Both
      etching efficacy and strength of the resins are important contributing factors in
      bonding of self-etching adhesives to unground enamel.

PMID- 11445212
TI  - Effect of remaining dentin thickness and the use of conditioner on micro-tensile
      bond strength of a glass-ionomer adhesive.
AB  - OBJECTIVES: The purpose of this study is to investigate the effect of remaining
      dentin thickness and the use of a 20% polyalkenoic acid conditioner on the micro
      tensile bond strength of a glass-ionomer adhesive to dentin. METHODS: Resin
      composite was bonded to flat dentin surfaces from 14 extracted human teeth using
      Fuji BOND LC (GC) with or without a polyalkenoic acid conditioner, then sectioned
      to thin slabs, trimmed into an hourglass shape with the area of the interface
      being approximately 1mm(2), and subjected to micro-tensile testing at a cross
      head speed of 1mm/min. Micro-tensile bond strengths were determined at three
      depth levels with a remaining dentin thickness of more than 3mm, between 2 and
      3mm, and less than 2mm. Failure modes of the broken interfaces were determined
      using field-emission scanning electron microscopy. RESULTS: The micro-tensile
      bond strength to dentin significantly improved when the remaining dentin
      thickness increased and the conditioner was used. When the conditioner was used
      (irrespective of remaining dentin thickness), failures mainly occurred adhesively
      at the interface between the adhesive and resin composite. When no conditioner
      was used, no adhesive failures between the adhesive and resin composite occurred,
      but failures occurred mainly adhesively between dentin and the adhesive, or mixed
      adhesive-cohesively. SIGNIFICANCE: The bonding effectiveness of the glass-ionomer
      adhesive tested was affected by the area of intertubular dentin available for
      micro-mechanical retention through hybrid-layer formation. Removal of the smear
      layer improved the bond strength of the adhesive to dentin.

PMID- 11445214
TI  - Introduction.

PMID- 11445213
TI  - Bonding of contemporary glass ionomer cements to dentin.
AB  - OBJECTIVE: The objective of this study was to investigate the microtensile bond
      strength (microTBS) of contemporary glass ionomer cements (GIC) to sound coronal
      dentin. METHODS: Three specimen teeth were prepared for each material tested:
      Fuji IX GP (GC), ChemFlex (Dentsply) and Ketac-Molar Aplicap (ESPE). GIC buildups
      were made according to the manufacturers' instructions. After being stored at 37
      degrees C, 100% humidity for 24h, the teeth were vertically sectioned into 1x1mm
      beams for microTBS evaluation. Representative fractured beams were prepared for
      scanning (SEM) and transmission electron microscopic (TEM) examination. RESULTS:
      Results of the microTBS test were: Fuji IX GP (12.4+/-8.6MPa), ChemFlex (15.0+/
      9.3MPa) and Ketac-Molar Aplicap (11.4+/-7.7MPa). One-way ANOVA and a multiple
      comparison test showed that ChemFlex had a statistically higher microTBS
      (p<0.05). SEM fractographic analysis showed that the predominant failure modes
      were interfacial and mixed failures. The GIC side of the fractured beams revealed
      dehydration cracks, a high level of porosity, and voids with an eggshell-like
      crust. TEM analysis of the demineralized dentin sides of the fractured beams
      revealed the presence of an intermediate layer along the GIC-dentin interface.
      This zone was present on the fractured dentin surface in the case of interfacial
      failure, and beneath GIC remnants in specimens that exhibited a mixed failure
      mode. SIGNIFICANCE: The findings suggest that the bonding of GIC to dentin is not
      weak and that the microTBS values probably represent the weak yield strengths of
      GICs under tension.

PMID- 11445215
TI  - Overview of the Third International Workshop on Swine Leukocyte Differentiation
      Antigens.
AB  - The aim of the Third International Workshop on Swine Leukocyte Differentiation
      Antigens (CD workshop), supported by the Veterinary Immunology Committee (VIC) of
      the International Union of Immunological Societies (IUIS), was to standardize the
      assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte
      differentiation antigens and to define new antibody clusters, using nomenclature
      in accordance with human and ruminant CD nomenclature, as agreed at the summary
      meeting of the Second International Swine CD Workshop in Davis, 1995: only mAb
      with proven reactivity for the orthologous porcine gene product or cross
      reactivity for the human gene products, were given the full CD nomenclature, all
      other allocations were prefixed with "w". As in previous workshops, the overall
      organization was entrusted to the chair and first author, with support by the
      chair of the previous workshop and second author. In addition to the existing 26
      pig leukocyte CD/SWC determinants established in previous workshops, this
      workshop established/confirmed another 11 CDs for pig leukocytes, identified by a
      total of 21 mAb: CD11R1 (2 mAb), CD11R2 (1 mAb), CD11R3 (4 mAb), wCD40 (1 mAb),
      wCD46 (4 mAb), wCD47 (3 mAb), wCD49d (1 mAb), CD61 (1 mAb), wCD92 (1 mAb), wCD93
      (1 mAb) and CD163 (2 mAb).

PMID- 11445216
TI  - Summary of the first round analyses of the Third International Workshop on Swine
      Leukocyte Differentiation Antigens.
AB  - The reactivity of 155 monoclonal antibodies submitted to the Third International
      Workshop on Swine Leukocyte Differentiation Antigens, together with 41 internal
      standards, was analysed by flow cytometry on 29 different pig cell targets as
      well as two human cell targets as a means of establishing suitable panels of
      monoclonal antibodies for more detailed clustering analyses by the various
      subsections of the workshop. Results were collected either without further
      gating, with gating based on FS/SS characteristics or with gating based on the co
      expression of a reference antibody in two-colour flow cytometry. The CD or SWC
      reactivity of the internal standards had been established in previous workshops.
      Data sets were subsequently analysed by statistical clustering using the
      Leucocyte Typing Database IV software. The resulting 18 cluster groups were
      allocated to the appropriate second round sections of the workshop, after
      reviewing the overall cellular reactivity of each cluster as well as the
      specificity of known standards which clustered in a group.

PMID- 11445217
TI  - Summary of workshop findings for porcine T-lymphocyte-specific monoclonal
      antibodies.
AB  - Fifty-seven monoclonal antibodies (mAb) selected after the first round analyses
      in the Third International Swine CD workshop for their possible reactivity with T
      lymphocyte specific antigens were further analysed in a second round. As target
      cells for flow cytometric analyses served peripheral blood mononuclear cells,
      nylon-wool enriched T-lymphocytes, thymocytes, splenocytes, and lymphocytes
      derived from Peyer's patches. These second round analyses revealed 15 different
      data sets. Together with 22 pre-selected data sets from the first round analyses
      with the whole panel of monoclonal antibodies, 37 data sets were used for the
      clustering of the respective mAb. Using the LTDB4 program, 19 preliminary
      clusters could be defined. Two clusters (C3 and C7) with 4 mAb showed no
      labelling of resting T-lymphocytes. Seven clusters (C1, C2, C4, C5, C6, C11, and
      C12) contain mAb (in total: 16 mAb) directed against subsets of CD4(-)CD8(-) T
      lymphocytes. These mAb seem to recognise antigens on porcine T-lymphocytes with T
      cell receptor (TcR) gamma/delta chains. Three clusters (C8, C9, C10, C13) seem to
      be artificial. They contain either mAb staining CD4(-)CD8(-) T-lymphocytes and
      low CD8+ cells (C8, C9), mAb with various reactivity (C10) and mAb with known
      differences in their reactivity (C13). Cluster C14 contains 3 mAb against the
      CD4a-epitope, C15 describes mAb directed against porcine CD8c-epitope whereas mAb
      against CD8a and CD8b-epitopes grouped in C19. The mAb found in C16 seem to
      recognise CD45R. Cluster C17 is composed of different standards directed against
      CD2, CD3, CD5 and wCD6. Two additional mAb recognising the CD2a-epitope could be
      enclosed. C18 contains two mAb directed against SWC2.

PMID- 11445218
TI  - Analysis of monoclonal antibodies reacting with molecules expressed on gammadelta
      T-cells.
AB  - Twenty-six monoclonal antibodies (mAbs) selected after the first round of
      analysis in the Third International Swine Workshop were grouped with additional
      mAbs from the first and second workshops and mAbs under study for further
      evaluation. Preparations of peripheral blood leukocytes were used in single and
      multicolor flow cytometric (FC) analyses. Six mAbs did not react with gammadelta
      T-cells. Two were negative for all tested specificities. Seven mAbs recognized
      molecules expressed on gammadelta T-cells that were not lineage restricted. One
      of these from the first workshop (2B11) yielded a pattern of labeling identical
      to a mAb under study (PGB73A). Ten mAbs were characterized in previous workshops
      and known to react with the gammadelta TCR or molecules expressed on subsets of
      gammadelta T-cells. One belonged to SWC4, two to SWC5, and one to SWC6. Two mAbs
      from the second workshop recognized a molecule or molecules expressed on subsets
      of gammadelta T-cells. A new mAb (PPT16) added late to the workshop following a
      request by the workshop chairs appeared to recognize a determinant expressed on
      the gammadelta TCR/CD3 molecular complex.

PMID- 11445219
TI  - Summary of workshop findings for porcine B-cell markers.
AB  - Based on cluster groups from the first-round analyses of the Third International
      Swine CD Workshop, 38 monoclonal antibodies (MAbs) including eight internal
      controls were analysed by flow cytometry (FCM) and immunohistochemistry (IH) in
      the second-round analysis of the B-cell section of this workshop. Targets in this
      section included peripheral blood lymphocytes and cells isolated from ileal
      Peyer's patches (PP), mesenteric lymph nodes (MLN) of adult animals, bone marrow
      cells from newborn piglets and thymus cells isolated from foetuses at day 105 of
      gestation. Immunohistochemistry of these 38 MAbs identified four sets, whose
      ligands were co-expressed with CD21, which showed a tissue distribution
      compatible with specificity for cells including those of the B-cell lineage.
      Another group of miscellaneous antibodies appeared to identify other cells,
      several antibodies were negative. Two-colour flow cytometry (2C-FCM) was carried
      out by pairing each antibody of interest with antibodies to SWC7, CD21, sIgM and
      a polyclonal rabbit anti-swine immunoglobulin antiserum (RaSwIg). The anti-CD21
      MAb BB6-11C9 (no. 20) and IAH-CC51 (no. 19), established in previous workshops,
      as well as the cross-reactive anti-human CD21 B-1y4 (no. 146), clustered together
      in FCM analyses of the first round and showed similar cellular distribution in
      IH. A further cluster was formed by the standard CC55 (no. 55) and 2A10/8 (no.
      102) submitted as SWC7 specific. The second SWC7 standard 2F6/8 (no. 100)
      clustered separately, but IH showed an identical pattern of reactivity to the
      other SWC7 MAb.Unfortunately, this work could not identify any other novel
      clusters with specificity for B-cells, as the statistical clustering of other
      MAbs could not be substantiated by IH or subsequent two-colour-FCM work. However,
      we could identify MAb with similar cellular distribution. The ligands for the
      cross-reactive anti-human CD40 G28.5 (no. 25) and STH224 (no. 153) were expressed
      on very similar targets, similarly the ligands for the MAb pair JM1H1 (no. 139)
      with BB6-10A10 (no. 142) and the MAb pair 3F7/11 (no. 115) with 1C2F10 (no. 187).

PMID- 11445220
TI  - Characterization of monoclonal antibodies recognizing immunoglobulin kappa and
      lambda chains in pigs by flow cytometry.
AB  - The existence of two types of the immunoglobulin (Ig) light chain in pigs was
      documented>30 years ago and has been confirmed by the cloning of porcine light
      chain genes homologous to human and murine Ig kappa (Igkappa) and Ig lambda
      (Iglambda). However, immunochemical reagents defining these two light chain
      isotypes have not been characterized. Here, we show that rabbit antisera specific
      for human Igkappa and Iglambda and certain anti-porcine light chain monoclonal
      antibodies (mAb) are useful in distinguishing light chain isotypes by flow
      cytometry (FCM). Porcine B cell lines L23 and L35 stained positive only with anti
      human Iglambda antiserum and were negative when tested using anti-human Igkappa
      antiserum. While mAbs K139.3E1, 1G6 and 27.7.1 also tested positive on these cell
      lines, mAb 27.2.1 did not. Therefore, FCM was used to examine the hypothesis that
      K139.3E1, 1G6 and 27.7.1 are Iglambda-specific whereas mAb 27.2.1 recognizes the
      Igkappa chain in pigs. Double staining of peripheral blood mononuclear cells
      (PBMC) with pairs of anti-light chain mAbs and using cocktails of anti-light
      chain mAbs and anti-human polyclonal antiserum, confirmed this hypothesis with
      the exception that mAb K139.3E1 appears to recognize only a subset of Iglambda(+)
      B cells in most pigs. In summary, we identified two pan-specific anti-pig
      Iglambda mAbs, one anti-lambda mAb that recognizes a lambda-light chain subset
      and one anti-pig Igkappa mAb.

PMID- 11445221
TI  - Summary of workshop findings for porcine myelomonocytic markers.
AB  - About 65 monoclonal antibodies (mAb) including 17 internal controls were analyzed
      for their ability to recognize and bind to various cells of the myelomonocytic
      lineage. Flow cytometry (FCM) utilizing both single and double staining, and
      immunoprecipitation (IP) assays were used in the analysis. About 38 of the mAb
      were reactive with myelomonocytic cells, resulting in nine clusters of interest.
      Although the exact identity of many of the molecules on the cells bound by the
      mAb remains undetermined, information obtained about the mAb analyzed in this
      workshop should be helpful in further identifying various populations of
      myelomonocytic cells and their stages of differentiation. Out of 12 mAbs with
      potential CD11 specificity, seven were assigned to three different swine specific
      alpha chains of the CD11/CD18 integrin heterodimer, the assignment of the
      remaining four was tentative. One antibody had a binding specificity consistent
      with SWC3 and one with SWC8. CD14 expression on pig cells was characterized with
      a panel of CD14-positive antibodies, two of these antibodies were assigned to
      swine CD14. Two antibodies were assigned to CD163. Further work is required to
      determine the antigens recognized by many of the other mAb.

PMID- 11445222
TI  - Workshop studies on monoclonal antibodies in the myeloid panel with CD11
      specificity.
AB  - Several putative anti-human and swine CD11-specific monoclonal antibodies (mAbs)
      were included in the myeloid section of the Third International Swine CD
      Workshop. Failure of clustering analysis to group these mAbs together prompted
      additional analyses to define the specificities of these mAb. Combination of one
      and two-color flow cytometry (FCM) and immunoprecipitation (IP) allowed the
      definition of the mAb into three CD11 groups. Cellular distribution of the
      molecules recognized by anti-human CD11b and c mAbs on swine cells proved to be
      significantly different from that found in humans.

PMID- 11445223
TI  - Differentiation of porcine myeloid bone marrow haematopoietic cell populations.
AB  - The myeloid panel of monoclonal antibodies (mAbs) submitted to the Third Swine CD
      Workshop were analysed for reactivity with bone marrow haematopoietic cells
      (BMHC). Using single and triple immunofluorescence labelling by flow cytometry
      (FCM), the mAbs were grouped according to their capacity to recognise myeloid
      cell populations and/or maturation stages. Group 1 consisted of mAbs labelling
      the majority of myeloid BMHC, including neutrophilic, eosinophilic and monocytic
      cells. The ligands for SWC3 and CD11b-like mAbs of group 1 showed a maturation
      dependent intensity of expression. The other antibodies of group 1 reacted with
      BMHC to give a sharp, single peak. Group 2 mAbs reacted only with monocytic
      cells. The anti-human CD49e mAb Sam-1 was the only mAb detecting the majority of
      monocytic cells, but not other BMHC. The mAbs in group 3 recognised antigens
      expressed on granulocytes, but not monocytes. The previously identified SWC8 in
      this group proved to be useful in differentiating major population of BMHC when
      cells were double labelled with the pan-myeloid SWC3. Other mAbs within group 3,
      such as MIL4 and TMG6-5 (an anti-human CD11b), only recognised subsets of
      neutrophils and eosinophils. Group 4 mAbs reacted with the more mature
      subpopulations of neutrophils and monocytes. Some of these antibodies might prove
      useful for assessment of cell maturity, such as anti-CD14 and the anti-human CD50
      mAb HP2/19.

PMID- 11445224
TI  - Swine platelet antigens: section report.
AB  - A total of 14 antibodies were found to label resting and/or activated swine
      platelets. Six recognized CD previously characterized for swine (CD29, CD41/61
      and CD46). One had been characterized for human cells (CD47). Two antibodies with
      CD14 and SLA class I specificity suggested by the donor as well as five blind
      antibodies were also positive on platelets. One antibody appeared to recognize
      the swine homologue to human CD47, and four remained unclustered.

PMID- 11445225
TI  - Monoclonal antibodies putatively recognising activation and differentiation
      antigens.
AB  - In the activation/maturation section, 46 monoclonal antibodies (mAbs) were
      analysed using freshly isolated as well as mitogen activated and recall antigen
      re-stimulated cells. A total of 10 internal standards as well as 6 antibodies
      with established reactivity for human cells, reported to cross-react with porcine
      leukocytes, were included in the panel. The standard antibodies were anti-CD25,
      CD44, CD45, SLA II, SWC1, SWC2, SWC7 and SWC8 reagents. The test panel contained
      antibodies with putative reactivity to CD25, SLA II and other mAbs directed
      against ill-defined targets. Single and double colour surface staining was
      performed in the attempt to group the mAbs tested into clusters of
      differentiation. Five new anti-class II reagents, two directed to SLA-DQ and
      three to SLA-DR, could be added to the previously established ones. One new anti
      CD25 as well as two new antibodies with SWC7 and SWC8 specificities,
      respectively, could also be added to the previously established ones. The
      identity of the two latter antibodies was also confirmed in other sections of
      this workshop (B-cell section for SWC7 antibodies and myeloid section for the
      SWC8 antibodies). The antibody JM2F12, in our hands, has shown strong
      similarities to the cross-reactive anti human-CD49f reagent. No other clusters
      were identified, as all remaining antibodies behaved in a different way on
      different target leukocyte populations. The second purpose of the section was
      fulfilled: interesting staining profiles of several antibodies on differentiating
      lymphocytes were recorded and are discussed here.

PMID- 11445226
TI  - Characterization of monoclonal antibodies assigned to the CD45 subgroup of the
      Third International Swine CD Workshop.
AB  - As a result of the first-round cluster analysis, a panel of 16 novel monoclonal
      antibodies (mAbs) was assigned for detailed analysis to the CD45 subgroup of the
      Third International Swine CD Workshop. The specificity of the mAbs was initially
      determined by examining their reactivity with Chinese hamster ovary (CHO) cells
      engineered to express individual isoforms of porcine CD45. These analyses
      indicated that seven of the mAbs (PG77A, PG96A, PG167A, PGB78A, 3C/9, MIL13, NHT
      101) recognized the portion of the CD45 molecule encoded by the A exon (CD45RA),
      while one (MIL15) was specific for that portion encoded by the C exon (CD45RC).
      In each case, the designation was supported by the demonstration that the
      molecular weight(s) of the recognized antigen(s) in porcine mononuclear cells, as
      determined by immunoprecipitation, corresponded to the predicted size(s)
      according to their specificity. As expected, a similar correlation was obtained
      for five standard mAbs whose specificity for either common or restricted epitopes
      of porcine CD45 had been established in previous workshops. Screening of the
      remaining 174 mAbs that comprised this workshop but were excluded from the CD45
      subgroup by cluster analysis failed to detect any additional ones reactive with
      the porcine CD45-expressing cells.

PMID- 11445227
TI  - Monoclonal antibodies raised to human cells--specificity for pig leukocytes.
AB  - A total of 27 monoclonal antibodies raised to human targets were included in the
      present Pig CD workshop. 14 of these had been tested in previous workshops and
      had been reported as cross-reactive, a further 13 had been reported as cross
      reactive during the Human Leukocyte Differentiation Antigens Workshop VI (HLDA
      VI) and/or by the donor (a commercial company submitting these mAb for validation
      by the workshop community). Of the 27 antibodies, three antibodies with
      previously reported reactivity for pig cells were eliminated from the workshop
      following preliminary tests due to lack of reactivity. Nine antibodies, although
      initially positive, gave inconsistent results during the course of the workshop.
      We found consistent reactivity for 15 antibodies. However, the cellular
      distribution of the target molecules on pig and human cells was shown to be
      different for three of these antibodies. These findings have important
      implications for the usefulness of these antibodies as research tools in the pig.

PMID- 11445228
TI  - Structure-activity relationships of novel peptides related to the antiarrhythmic
      peptide AAP10 which reduce the dispersion of epicardial action potential
      duration.
AB  - We report the first study on short peptide structure-activity relationships (SAR)
      for the antiarrhythmic peptide AAP10 and its putative receptor. Synthetic
      improvements on the natural antiarrhythmic peptide AAPnat (H-Gly-Pro-Hyp-Gly-Ala
      Gly) isolated from bovine atria led us to the synthesis of our lead molecule
      AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-NH(2)) which reduces dispersion of epicardial
      potential duration and acts antiarrhythmically in isolated rabbit hearts. The aim
      of our study was to elucidate structure-activity relationships for AAP10 based on
      Langendorff experiments and molecular modeling. Mutation of the amino acid
      sequence led to 11 different peptides which were tested analogous to the lead
      molecule. Among these new synthetic peptides various including the cyclopeptide
      cAAP10RG, cyclo[CF(3)C(OH)-Gly-Ala-Gly-Hyp-Pro-Tyr] showed promising activities.
      (supported by the DFG and Koln-Fortune)

PMID- 11445229
TI  - Effects of cod bradykinin and its analogs on vascular and intestinal smooth
      muscle of the Atlantic cod, Gadus morhua.
AB  - The effects of [Arg(0),Trp(5),Leu(8)]-BK (cod [Arg(0)]BK) on vascular
      preparations from branches of the cod celiac artery and on longitudinal smooth
      muscle preparations from the cod intestine were investigated. Cod [Arg(0)]BK (3 x
      10(-8) M) caused a relaxation of the celiac artery precontracted with adrenaline.
      The relaxation was abolished by the cyclooxygenase inhibitor indomethacin,
      suggesting that the effect is mediated through the release of prostaglandins, but
      there was no evidence for the involvement of leukotrienes or nitric oxide in the
      response. In the intestinal preparations, cod [Arg(0)]BK produced concentration
      dependent contractions (pD(2) = 8.28 +/- 0.16). Experiments with N-terminally and
      C-terminally truncated analogs and with alanine-substituted analogs of cod
      [Arg(0)]BK demonstrate that the central amino acid Gly(4) and the C-terminal
      amino acids Leu(8) and Arg(9) are the most important in determining the
      conformation of the peptide that interacts with the receptor. The results
      indicate that the ligand binding properties of the cod BK receptor are
      considerably different from the receptor present in trout tissues and may
      resemble those of the mammalian B(2) receptor more closely.

PMID- 11445230
TI  - Comparison of neurokinin SP with diazepam in effects on memory and fear
      parameters in the elevated T-maze free exploration paradigm.
AB  - The elevated T-maze was combined with a free exploration protocol, which, in
      contrast to the conventional procedure, dispenses with handling of the animals
      during the experimental sessions. This allows measurement of fear indexes derived
      from the elevated plus-maze as well as assessment of acquisition of open arm
      avoidance and open arm escape in one continuous session. Retention of the
      different fear-responses is measured 72 h later without drug treatment. In order
      to assess the effects of two known anxiolytics in this paradigm, rats received an
      IP injection of diazepam (1 to 4 mg/kg), substance P (5 to 500 microg/kg) or
      vehicle (1 ml/kg) and were tested on the T-maze for 5 min. Diazepam elevated open
      arm activity, indicative of an anxiolytic effect. The drug also increased the
      latency to escape from the open arms, but did not significantly affect
      acquisition of open arm avoidance. During the retention trial, diazepam in higher
      doses impaired the performance of both fear-responses, suggestive of an
      anterograde amnesic effect. Substance P did not influence acquisition and
      retention of open arm avoidance and escape. However, in high doses, the peptide
      increased the sojourn time in the central arena of the maze, indicating reduced
      fear and, hence, a dissociation between anxiolytic and amnesic effects. The
      present findings demonstrate that the elevated T-maze free exploration paradigm
      is sensitive to anxiolytic and memory-modulating effects of drugs.

PMID- 11445231
TI  - Antidepressant-type effect of the NK3 tachykinin receptor agonist aminosenktide
      in mouse lines differing in endogenous opioid system activity.
AB  - The influence of the tachykinin NK3 receptor agonist, aminosenktide on the
      immobility in the forced swimming test was studied in mouse lines selectively
      bred for divergent magnitudes of stress-induced analgesia. The high analgesia
      (HA) line is known to display enhanced, and the low analgesia (LA) line displays
      reduced activity of the opioid system. Aminosenktide at doses of 125 microg/kg or
      250 microg/kg intraperitoneally (IP) reduced, in naltrexone-reversible manner,
      the immobility more of opioid receptor-dense HA than of unselected mice, but was
      ineffective in the opioid receptor-deficient LA line. The effect of aminosenktide
      was quite similar to the antiimmobility action of desipramine (10 mg/kg IP), a
      prototypic antidepressant agent. None of the compounds increased animals'
      locomotion as found with an open field test; therefore their antiimmobility
      effect cannot be attributed to a change in general motility. The results claim
      that aminosenktide causes an antidepressant effect, and endogenous opioids are
      involved in this process.

PMID- 11445232
TI  - Anxiogenesis induced by nitric oxide synthase inhibition and anxiolytic effect of
      melanin-concentrating hormone (MCH) in rat brain.
AB  - In this study, the involvement of nitric oxide (NO) in the mechanism of anxiety
      was investigated. The rats received an intraamygdaline or intrahippocampal
      injection of the nitric oxide synthase inhibitor, N(G)-nitro-l-arginine (L
      NOARG), and were then tested in the plus-maze test. L-NOARG induced a decrease in
      the time spent by rats in the open arms. Conversely, the administration of the
      melanin-concentrating hormone (MCH) into these structures increased the number of
      entries into the open arms as well as the time spent on them. MCH injected in
      rats pretreated with L-NOARG also was able to revert the anxiogenic effects of L
      NOARG in amygdala.

PMID- 11445233
TI  - Asphyxia-induced release of alpha-melanocyte-stimulating hormone in newborn pigs.
AB  - Asphyxia and reperfusion induced changes in the plasma and cerebrospinal fluid
      (CSF) concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH) were
      studied in newborn pigs using a specific radioimmunoassay technique.
      Cardiovascular and metabolic failure induced by neonatal asphyxia resulted in a 3
      fold, significant (P < 0.05) increase in plasma alpha-MSH levels, whereas the
      hormone concentration in CSF was significantly (P < 0.05) reduced by 50% during
      postasphyxial reperfusion. Our data indicate an asphyxia-induced release of alpha
      MSH, and suggest a discordant regulation of plasma and CSF concentrations in
      newborn pigs.

PMID- 11445234
TI  - An oxidation resistant radioligand for corticotropin-releasing factor receptors.
AB  - The methionine residues in Tyr-corticotropin-releasing factor (CRF) and Tyr
      sauvagine radioligands are subject to oxidation, which renders them biologically
      inactive. Therefore [Tyr(0,) Gln(1,) Leu(17)]sauvagine (YQLS), in which the
      methionine was replaced with leucine was synthesized and labeled with (125)Iodine
      using chloramine-T. Mass spectroscopy revealed that chloramine-T-treatment did
      not oxidize YQLS. (125)I-YQLS bound with high affinity to cells expressing the
      murine CRF receptor 1 (CRFR1), CRF receptor 2 (CRFR2), and the mouse brain
      regions known to express both CRF receptors. (125)I-YQLS chemically cross-linked
      to CRFR1. In conclusion, (125)I-YQLS is oxidation-resistant, high affinity
      radioligand that can be chemically cross-linked to the CRF receptors.

PMID- 11445235
TI  - Effects of forebrain microinjection of cholecystokinin on dopamine cell firing
      rate.
AB  - In anesthetized rats, midbrain dopamine (DA) neuronal firing rate was
      differentially sensitive to focal brain microinjection of cholecystokinin
      peptides (CCK-4 and CCK-8) and N-methyl-D-aspartate (NMDA) into nucleus
      accumbens, amygdala and prefrontal cortex. Whereas changes in DA neuronal firing
      rate were frequently observed in response to intra-amygdalar microinjection of
      CCK peptides, NMDA was most effective in eliciting changes in DA neuronal
      activity following intra-accumbal microinjection. Thus, stimulation of amygdalar
      CCK receptors and accumbal excitatory amino acid receptors may participate in the
      afferent regulation of midbrain DA neuronal function.

PMID- 11445236
TI  - Colocalization of GABA, enkephalin and neuropeptide Y in the tectum of the green
      frog Rana esculenta.
AB  - The colocalization of GABA, enkephalin and neuropeptide Y immunoreactivity in
      neurons in the pretectal area and in the mesencephalic tectum of the green frog
      (Rana esculenta) was studied. Several Met-enkephalin immunoreactive perikarya
      were found in layer 6 of the tectum and every third of these neurons showed GABA
      ir as well. Colocalization of GABA and NPY could also be shown in half of the
      neuropeptide Y immunopositive cells in the 6th layer of the tectum, but only a
      few cells were double stained in layers 9 and 4. In the pretectal area no
      colocalization of the investigated peptides and GABA was found.

PMID- 11445237
TI  - Antinociceptive effect of somatostatin microinjected into caudate putamen.
AB  - The effects of somatostatin microinjected bilaterally and unilaterally (left or
      right) at a dose of 10, 50 and 100 ng into the caudate putamen of male Wistar
      rats on nociception (analgesy-meter test) were studied. Somatostatin injected
      into caudate putamen resulted in analgesia. Bilateral microinjections of
      somatostatin significantly increased the pain threshold in a dose-dependent
      manner, i.e. somatostatin exerted antinociceptive effect. The pain threshold
      after left-side microinjections was significantly higher than that after
      injections into right-side. These findings suggest antinociceptive and asymmetric
      effects of somatostatin on pain in the caudate putamen.

PMID- 11445238
TI  - Identification of neuropeptide FF-related peptides in rodent spinal cord.
AB  - Peptides which should be generated from the neuropeptide FF (NPFF) precursor were
      identified in mouse and rat spinal cord, by using reverse phase high pressure
      liquid chromatography with radioimmunoassay and electrospray mass spectrometry
      detection. In both species, two octapeptides, NPFF (Phe-Leu-Phe-Gln-Pro-Gln-Arg
      Phe-amide) and NPSF (Ser-Leu-Ala-Ala-Pro-Gln-Arg-Phe-amide) were identified but a
      longer peptide NPA-NPFF (Asn-Pro-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide) was
      present at the highest concentration in rat spinal cord. In mouse, the homologous
      peptide, SPA-NPFF (Ser-Pro-Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide) was not
      detected. Both peptides NPFF and NPSF reverse morphine-induced analgesia in the
      tail flick test. Our data reveal species differences in the maturation of NPFF
      precursor.

PMID- 11445239
TI  - MALDI-PSD-MS analysis of the phosphorylation sites of caseinomacropeptide.
AB  - Caseinomacropeptide (CMP) is a 64 amino acid polypeptide corresponding to kappa
      casein 106-169. CMP naturally exists in several forms due to extensive
      posttranslational modifications including glycosylation and phosphorylation. The
      aglycosylated, phosphorylated form of CMP has been shown to exhibit antibacterial
      activity. The aim of this study was to use matrix assisted laser
      desorption/ionization post source decay mass spectrometry (MALDI-PSD-MS) to
      identify the phosphorylation sites in the CMP sequence. CMP was isolated from a
      chymosin digest of casein by HPLC and then digested with endoproteinase Glu-C to
      generate peptides suitable for MALDI-PSD-MS analysis. This analysis showed that
      CMP is fully phosphorylated at Ser(149) and only partially phosphorylated at
      Ser(127.) Dehydroalanyl residues corresponding to the phosphoserines of CMP were
      detected upon MALDI-PSD-MS analysis suggesting that the phosphoryl bond in
      phosphoserine is very labile during PSD analysis such that the phosphoryl group
      may be lost before backbone fragmentation.

PMID- 11445240
TI  - Neuropeptides interact with glycolipid receptors: a surface plasmon resonance
      study.
AB  - Using Surface Plasmon Resonance (SPR) we investigated the interaction of seven
      neuropeptides with different characteristics and beta-amyloid (Abeta42) peptide,
      with membranes containing gangliosides. A wide range of affinities characterized
      the bindings (K(D) = 10(-3)- 10(-7) M), following the scheme: for GM1, Abeta42 >
      DYN > SP = GAL = SOM = BRD > OXY = ENK; for GD1a, Abeta42 = DYN = GAL > SP = SOM
      = BRD = OXY > ENK and for GT1b, Abeta42 > DYN > SP = GAL > SOM = BRD = OXY > ENK.
      The ganglioside sugar moiety, specifically the sialic acid, had an important role
      in the interactions. In general the affinities were higher with polysialo, than
      with monosialo gangliosides. The sensorgrams describing the interactions of
      Abeta42 and SP with gangliosides differed from the interactions of the other
      studied peptides. Ca(2+) promoted changes in peptide-glycolipid interactions.

PMID- 11445241
TI  - Circulating sensory peptide levels within 24 h of human bone fracture.
AB  - We designed this study to examine the circulatory levels of wound modulatory
      peptides [substance P (SP), calcitonin gene related peptide (CGRP] in patients
      with muscle injuries with bone fractures and within 24 h of the injury. The
      peripheral plasma levels of these sensory nerve peptides were measured on
      hospital admission (OA) and 24 h post-injury (PI), using ELISA technique. Mean
      (s.d) ng/liter of CGRP was higher in patients OA (270 +/- 199), and PI (205 +/-
      176); than the controls (3 +/- 81) P < 0.05. Substance P also increased in the
      patients OA: 101 +/- 50; PI: 46 +/- 3 than controls [8 +/- 9] P < 0.001. Elastase
      (predictor of posttraumatic complication) was examined and there was no
      significant differences between patients and control samples (P = NS). This study
      shows that sensory nerve peptides are increased in bone fracture related injuries
      up to 24 h after injury. An intact nociceptor system of primary afferent sensory
      nerves is important for the initiation of the inflammatory process and successful
      tissue repair as dysfunction of this system could be a contributing factor for a
      delayed wound healing.

PMID- 11445242
TI  - PACAP activates PKA, PKC and Ca(2+) signaling cascades in rat neuroepithelial
      cells.
AB  - Several studies have reported that the PAC(1) receptor (PAC1-R), the specific
      receptor for PACAP, is expressed at early developmental stages. Here, we describe
      that the cytosolic Ca(2+) concentration ([Ca(2+)](i)) was increased by PACAP, but
      not VIP, in a concentration range from 10(-12) to 10(-8) M via the PAC(1)-R in
      isolated single cells from the rat neural fold. This activation of the cells by
      PACAP was mimicked by agonists and inhibited by antagonists of the cAMP/PKA and
      PLC/PKC cascades. These data indicate that PACAP/PAC(1)-R is linked to
      [Ca(2+)](i) signaling via two G-protein-coupled protein kinase pathways and may
      thereby play an important role in early neurodevelopment.

PMID- 11445243
TI  - GRP-receptor-mediated signal transduction, gene expression and DNA synthesis in
      the human pancreatic adenocarcinoma cell line HPAF.
AB  - Bombesin-like peptides have been implicated as growth factors in various human
      cancers. Human adenocarcinoma cell lines (Capan-1, Capan-2, MiaPaCa-2 and HPAF)
      were tested to determine whether they express the gastrin-releasing peptide
      preferring bombesin receptor (GRPR) and neuromedin B-preferring bombesin receptor
      (NMBR). Using RT-PCR the highest level of GRP receptor mRNA was found in HPAF
      cells. NMB receptor mRNA expression moderate in all cell lines investigated. We
      therefore selected the HPAF cell line to investigate whether bombesin treatment
      affects intracellular Ca(2+) ([Ca(2+)](i)), cAMP level, DNA synthesis as a
      measure of cell proliferation, and expression of three transcription factors: c
      fos, c-myc and high mobility group protein IY (HMG-I(Y)).Bombesin administration
      led to an immediate increase in free intracellular Ca(2+) concentration
      ([Ca(2+)](i)) but did not change cAMP levels. The peptide also enhanced
      [(3)H]thymidine incorporation in HPAF cells (but not in the other cell lines), an
      effect that was concentration dependent, reaching 36 +/- 5% stimulation over
      control values at 24 h with an EC(50) of 2.27 x 10(-12) M. Furthermore, bombesin
      stimulated c-fos, c-myc and HMG-I(Y) expression in a time-dependent manner: the c
      fos mRNA level increased dramatically in the first 30 min of exposure, then
      returned to basal level within 2 h, while the c-myc and HMG-I(Y) mRNA levels
      peaked at 2 h and 4h, respectively. All actions of bombesin were blocked by BME
      (D-Phe(6)-bombesin-(6-13)-methylester), a selective GRP receptor antagonist, but
      not by the NMB receptor antagonist BIM-23127 (D-Nal-cyclo[Cys-Tyr-D-Trp-Orn-Val
      Cys]-Nal-NH(2)). We conclude that HPAF cells express mRNA for GRP receptors and
      that functional receptors are present in the cell membrane. The occupation of
      these receptors leads to a sequence of intracellular events involving rapid
      mobilization of intracellular Ca(2+), expression of c-fos, c-myc and HMG-I(Y)
      mRNA, and stimulation of cell proliferation. Conversely, although NMB receptor
      mRNA can be detected, its actual translation to functional receptors does not
      reach a detectable level.

PMID- 11445244
TI  - Permeability of the peptidic GH secretagogues hexarelin and EP 51389, across rat
      jejunum.
AB  - The intestinal permeability of hexarelin and EP 51389, two growth hormone
      releasing hexa- and tri- peptide analogues, was assessed in vitro with side-by
      side diffusion chambers in the apical-to-basolateral (AP-to-BL) and in the
      basolateral-to-apical (BL-to-AP) direction using excised rat jejunal segments.
      The effect of EP 51389 on P-glycoprotein (P-gp) was evaluated by rhodamine 123
      accumulation on monolayers of CH(R)C5 cells with increasing concentrations of EP
      51389. Hexarelin and EP 51389 permeability were found to be < 1%. Permeability
      coefficients (P(app)) were 18.87 +/- 2.86 (x10(-7) cm/s) and 5.87 +/- 0.45 (x10(
      7) cm/s) for hexarelin and EP 51389, respectively. Bidirectional studies revealed
      that hexarelin transport was similar in both directions. EDTA did not influence
      hexarelin permeability. Permeability was predominantly secretory for EP 51389 as
      P(app) in the BL-to-AP direction [32.56 +/- 6.11 (x10(-7) cm/s)] was greater than
      AP-to-BL. Confirming involvement of a secretory transport system, chlorpromazine
      inhibited EP 51389 transport across the jejunum. EP 51389 inhibited P-gp in a
      dose dependent manner resulting in the intracellular accumulation of rhodamine in
      CH(R)C5 cells. These results suggest that: 1) the intestinal permeability of
      hexarelin and EP 51389 is poor; 2) the passage of hexarelin is mainly via a
      transcellular passive pathway since the contribution of paracellular permeability
      to the overall permeability is rather low; 3) P-gp may act as a potential barrier
      for the intestinal absorption of EP 51389.

PMID- 11445245
TI  - GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due
      to VIP receptor agonist activity.
AB  - Growth hormone (GH) is used or is being evaluated for efficacy in treatment of
      short stature, aspects of aging, cardiac disorders, Crohn's disease, and short
      bowel syndrome. Therefore, we synthesized several stable growth hormone-releasing
      factor (GRF) analogues that could be therapeutically useful. One potent analog,
      [D-Ala(2),Aib(8, 18,)Ala(9, 15, 16, 22, 24-26,)Gab(27)]hGRF(1-27)NH(2) (GRF-6),
      with prolonged infusion caused severe diarrhea in monkeys; however, it had no
      side-effects in rats. Because GRF has similarity to VIP/PACAP and VIPomas cause
      diarrhea, this study investigated the ability of this and other GRF analogues to
      interact with the VIP/PACAP receptors. Rat VPAC(1)-R (rVPAC(1)-R), human VPAC(1)
      R (hVPAC(1)-R), rVPAC(2)-R and hVPAC(2)-R stably transfected CHO and PANC 1 cells
      were made and T47D breast cancer cells containing native human VPAC(1)-R and AR4
      2J cells containing PAC(1)-R were used. hGRF(1-29)NH(2) had low affinity for both
      rVPAC(1)-R and rVPAC(2)-R while VIP had a high affinity for both receptors. GRF-6
      had a low affinity for both rVPAC(1)-R and rVPAC(2)-R and very low affinity for
      the rPAC(1)-R. VIP had a high affinity, whereas hGRF(1-29)NH(2) had a low
      affinity for both hVPAC(1)-R and hVPAC(2)-R. In contrast GRF-6, while having a
      low affinity for hVPAC(2)-R, had relatively higher affinity for the hVPAC(1)-R.
      In guinea pig pancreatic acini, all GRF analogues were full agonists at the
      VPAC(1)-R causing enzyme secretion. These results demonstrate that in contrast to
      native hGRF(1-29)NH(2,) GRF-6 has a relatively high affinity for the human
      VPAC(1)-R but not for the human VPAC(2)-R, rat VPAC(1)-R, rat VPAC(2)-R or rat
      PAC(1)-R. These results suggest that the substituted GRF analog, GRF-6, likely
      causes the diarrheal side-effects in monkeys by interacting with the VPAC(1)-R.
      Furthermore, they demonstrate significant species differences can exist for
      possible therapeutic peptide agonists of the VIP/PACAP/GRF receptor family and
      that it is essential that receptor affinity assessments be performed in human
      cells or from a closely related species.

PMID- 11445246
TI  - C-type natriuretic peptide system in rabbit oviduct.
AB  - C-type natriuretic peptide (CNP), a third member of the natriuretic peptide
      family, is known to be distributed mainly in brain and vascular endothelium and
      is considered to act as a local regulator in many tissues. The purpose of this
      study was to determine the presence of CNP system and its biological function in
      rabbit oviduct. The serial dilution curve of tissue extracts was parallel to the
      standard curve of CNP((1-22)) and a major peak of molecular profile of tissue
      extracts by HPLC was CNP((1-53)). mRNA of CNP which was the same size as positive
      control was also detected by Southern blot analysis. CNP increased the production
      of 3',5'-cyclic guanosine monophosphate (cGMP) in the purified membrane of
      oviduct, which was more in membranes derived from the isthmic portion than in the
      ampullar portion. The presence of mRNAs of natriuretic peptide receptor-A (NPR-A)
      and NPR-B was demonstrated by RT-PCR. Synthetic CNP((1-22)) inhibited both
      frequency and amplitude of basal motility of oviduct in a dose-dependent manner.
      The inhibitory effect of CNP on the basal motility was more potent in the isthmic
      portion than in the ampullar portion. These results demonstrate the presence of
      CNP system in the oviduct and regional differences in motility inhibition by CNP
      between isthmic and ampullar portions. Therefore, these findings suggest the
      possible existence of a CNP system that may exert a local regulator of basal
      motility, either alone or in concert with other hormones.

PMID- 11445247
TI  - Regulation of TRH and TRH-related peptides in rat brain by thyroid and steroid
      hormones.
AB  - To investigate the possibility that TRH (pGlu-His-Pro-NH(2)) and EEP (pGlu-Glu
      Pro-NH(2)) contribute to the behavioral and mood changes attending
      hypothyroidism, hyperthyroidism and hypogonadism, we have treated young, adult,
      male Sprague-Dawley rats (5/group, 250 g bw at time of sacrifice) for one week
      with either daily ip injections of saline, 5 microg T(4), 3 mg PTU or castration.
      Immunoreactivity for TRH (TRH-IR), TRH-Gly (pGlu-His-Pro-Gly, a TRH precursor),
      EEP and Ps4 (prepro-TRH-derived TRH-enhancing peptide) was measured in 8 brain
      regions by RIA. Castration reduced the Ps4-IR levels in hippocampus by 80%. High
      pressure liquid chromatography revealed that in many brain regions EEP-IR and TRH
      IR consisted of a mixture of TRH and other TRH-like peptides including EEP,
      Val(2)-TRH, Tyr(2)-TRH, Leu(2)-TRH and Phe(2)-TRH. Transition from the
      hyperthyroid to the hypothyroid state increased the Val(2)-TRH and Tyr(2)-TRH
      levels in the accumbens by 10-fold and 15-fold, respectively, and the
      corresponding ratios for the pyriform cortex increased 9-fold and 12-fold,
      respectively. Hypothyroidism and castration reduced the levels of TRH and the
      majority of other TRH-like peptides in the entorhinal cortex. This is the first
      report that thyroid and steroid hormones alter the levels of TRH, prepro-TRH
      derived peptides, and a newly discovered array of TRH-like neuropeptides in
      limbic brain regions.

PMID- 11445248
TI  - Expression of urotensin II and urotensin II receptor mRNAs in various human tumor
      cell lines and secretion of urotensin II-like immunoreactivity by SW-13
      adrenocortical carcinoma cells.
AB  - Urotensin II is the most potent vasoconstrictor peptide identified so far.
      Expression of urotensin II and urotensin II receptor mRNAs was studied in various
      human tumor cell lines by reverse transcriptase polymerase chain reaction (PCR)
      method. Secretion of urotensin II by these tumor cells was studied by
      radioimmunoassay. The tumor cell lines studied were T98G glioblastoma cells, IMR
      32 neuroblastoma cells, NB69 neuroblastoma cells, BeWo choriocarcinoma cells, SW
      13 adrenocortical carcinoma cells, DLD-1 colorectal adenocarcinoma cells and HeLa
      cervical cancer cells. Urotensin II mRNA was expressed in 6 tumor cell lines
      except for NB69 neuroblastoma cells. Urotensin II receptor mRNA was expressed in
      all 7 tumor cell lines. A significant amount of urotensin II-like
      immunoreactivity was detected only in the culture medium of SW-13 adrenocortical
      carcinoma cells by radioimmunoassay. Sephadex G-50 column chromatography showed
      that the urotensin II-like immunoreactivity in the culture medium extract was
      eluted earlier than synthetic human urotensin II, suggesting that SW-13 cells
      secreted higher molecular weight materials, perhaps partially processed forms of
      the urotensin II precursor. Reverse phase high-performance liquid chromatography
      (HPLC) showed three immunoreactive peaks, one of which was eluted in the position
      of urotensin II. The present study has shown for the first time expression of
      urotensin II and urotensin II receptor mRNAs in various tumor cell lines and the
      secretion of urotensin II-like immunoreactivity by SW-13 adrenocortical carcinoma
      cells.

PMID- 11445249
TI  - Met-enkephalin levels during PTCA-induced myocardial ischemia.
AB  - Met-enkephalin (Met-enk) has been demonstrated to modulate myocardial-ischemia
      mechanisms via the opioid receptors, but no studies are now available on Met-enk
      levels in the coronary circulation. In this experience Met-enk levels were
      evaluated in aortic root and in coronary sinus at baseline (T0), during PTCA
      induced transient ischemia (T1) and during reperfusion (T2). No significant
      differences were found at any time. Thus, it appears that there is no Met-enk
      extraction from the coronary circulation during provoked myocardial ischemia and
      no Met-enk release from the ischemic heart.

PMID- 11445250
TI  - Evolution of the insulin molecule: insights into structure-activity and
      phylogenetic relationships.
AB  - The conformation of insulin in the crystalline state has been known for more than
      30 years but there remains uncertainty regarding the biologically active
      conformation and the structural features that constitute the receptor-binding
      domain. The primary structure of insulin has been determined for at least 100
      vertebrate species. In addition to the invariant cysteines, only ten amino acids
      (GlyA1, IleA2, ValA3, TyrA19, LeuB6, GlyB8, LeuB11, ValB12, GlyB23 and PheB24)
      have been fully conserved during vertebrate evolution. This observation supports
      the hypothesis derived from alanine-scanning mutagenesis studies that five of
      these invariant residues (IleA2, ValA3, TyrA19, GlyB23, and Phe24) interact
      directly with the receptor and five additional conserved residues (LeuB6, GlyB8,
      LeuB11, GluB13 and PheB25) are important in maintaining the receptor-binding
      conformation. With the exception of the hagfish, only conservative substitutions
      are found at B13 (Glu --> Asp) and B25(Phe --> Tyr). In contrast, amino acid
      residues that were also considered to be important in receptor binding based upon
      the crystal structure of insulin (GluA4, GlnA5, AsnA21, TyrB16, TyrB26) have been
      much less well conserved and are probably not components of the receptor-binding
      domain. The hypothesis that LeuA13 and LeuB17 form part of a second receptor
      binding site in the insulin molecule finds some support in terms of their
      conservation during vertebrate evolution, although the site is probably absent in
      some hystricomorph insulins. In general, the amino acid sequences of insulins are
      not useful in cladistic analyses especially when evolutionary distant taxa are
      compared but, among related species in a particular order or family, the presence
      of unusual structural features in the insulin molecule may permit a meaningful
      phylogenetic inference. For example, analysis of insulin sequences supports
      monophyletic status for Dipnoi, Elasmobranchii, Holocephali and
      Petromyzontiformes.

PMID- 11445251
TI  - Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's
      disease pathology.
AB  - Nucleolin is a major multifunctional nuclear phosphoprotein that is
      phosphorylated by Cdc2 kinase in mitosis and that participates in a number of
      cellular processes. The monoclonal antibody TG-3 generated against
      neurofibrillary tangles (NFT) found in Alzheimer's disease (AD) is highly
      specific for mitotic cells in culture. We here demonstrate that phosphorylation
      of nucleolin by Cdc2 kinase generates the TG-3 epitope. The unique pool of TG-3
      immunoreactive nucleolin appears abruptly during the prophase. It is associated
      with chromosomes through the metaphase and it gradually disappears during
      separation of chromosomes and exit from mitosis. In the brain, nucleolin was
      localized not only to nuclei but also to neuronal cytoplasm, and it is a marker
      for early NFT. In patients with AD, Cdc2 phosphorylated nucleolin was present in
      NFT. These findings suggest that phosphorylation of nucleolin by Cdc2 kinase is a
      critical event and the point of convergence of two distinct pathways, mitosis and
      neurodegeneration.

PMID- 11445252
TI  - Hippocampal formation glucose metabolism and volume losses in MCI and AD.
AB  - We used MRI volume sampling with coregistered and atrophy corrected FDG-PET scans
      to test three hypotheses: 1) hippocampal formation measures are superior to
      temporal neocortical measures in the discrimination of normal (NL) and mild
      cognitive impairment (MCI); 2) neocortical measures are most useful in the
      separation of Alzheimer disease (AD) from NL or MCI; 3) measures of PET glucose
      metabolism (MRglu) have greater diagnostic sensitivity than MRI volume. Three
      groups of age, education, and gender matched NL, MCI, and AD subjects were
      studied. The results supported the hypotheses: 1) entorhinal cortex MRglu and
      hippocampal volume were most accurate in classifying NL and MCI; 2) both imaging
      modalities identified the temporal neocortex as best separating MCI and AD,
      whereas widespread changes accurately classified NL and AD; 3) In most between
      group comparisons regional MRglu measures were diagnostically superior to volume
      measures. These cross-sectional data show that in MCI hippocampal formation
      changes exist without significant neocortical changes. Neocortical changes best
      characterize AD. In both MCI and AD, metabolism reductions exceed volume losses.

PMID- 11445253
TI  - Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1
      receptor in Alzheimer's dementia.
AB  - We investigated the immunohistochemical alterations of angiotensin converting
      enzyme (ACE), angiotensin II and AT1 receptor in the parietal cortex in
      Alzheimer's dementia (AD) to reveal the contributive role of the brain renin
      angiotensin system in the disease process. In controls, ACE, angiotensin II and
      AT1 immunoreactivities were localized to pyramidal neurons of the cortex. The
      staining intensity was distinctly increased in AD for all three antigens,
      involving predominantly cortical layer V, which may reflect the enhanced brain
      renin-angiotensin system activity in the disease process. In addition, a
      prominent perivascular ACE and angiotensin II immunoreactivity surrounding some
      cortical vessels in aged controls and AD patients points to an underlying
      microvascular pathology in the process of neurodegeneration.

PMID- 11445254
TI  - Decreased brain levels of 2',3'-cyclic nucleotide-3'-phosphodiesterase in Down
      syndrome and Alzheimer's disease.
AB  - In Down syndrome (DS) as well as in Alzheimer's disease (AD) oligodendroglial and
      myelin alterations have been reported. 2',3'-cyclic nucleotide-3'
      phosphodiesterase (CNPase) and carbonic anhydrase II (CA II) are widely accepted
      as markers for oligodendroglia and myelin. However, only data on CNPase activity
      have been available in AD and DS brains so far. In our study we determined the
      protein levels of CNPase and CA II in DS, AD and in control post mortem brain
      samples in order to assess oligodendroglia and myelin alterations in both
      diseases. We used two dimensional electrophoresis to separate brain proteins that
      were subsequently identified by matrix assisted laser desorption and ionization
      mass-spectroscopy (MALDI-MS). Seven brain areas were investigated (frontal,
      temporal, occipital and parietal cortex, cerebellum, thalamus and caudate
      nucleus). In comparison to control brains we detected significantly decreased
      CNPase protein levels in frontal and temporal cortex of DS patients. The level of
      CA II protein in DS was unchanged in comparison to controls. In AD brains levels
      of CNPase were decreased in frontal cortex only. The level of CA II in all brain
      areas in AD group was comparable to controls. Changes of CNPase protein levels in
      DS and AD are in agreement with the previous finding of decreased CNPase activity
      in DS and AD brain. They probably reflect decreased oligodendroglial density
      and/or reduced myelination. These can be secondary to disturbances in
      axon/oligodendroglial communication due to neuronal loss present in both
      diseases. Alternatively, reduced CNPase levels in DS brains may be caused by
      impairment of glucose metabolism and/or alterations of thyroid functions.

PMID- 11445255
TI  - Increased alpha 2-adrenergic receptor binding in locus coeruleus projection areas
      in dementia with Lewy bodies.
AB  - Clinical studies suggest involvement of brain noradrenergic systems in the
      pathophysiology of disruptive agitation in Alzheimer's disease (AD). This
      behavioral problem is even more prevalent in dementia with Lewy bodies (DLB).
      Here we used receptor autoradiography with [(125)I]para-iodoclonidine to estimate
      alpha-2 adrenergic receptor (A2R) density in locus coeruleus (LC) projection
      areas in postmortem brain tissue from age and gender comparable groups of DLB (n
      = 6), AD (n = 5) and normal (n = 7) subjects. LC neuronal loss was substantial
      and equivalent in DLB and AD. A2R density was greater in DLB than in normals in
      the deep layers of the frontal cortex. A2R density was greater in DLB than in AD
      in hippocampus (CA-1, CA-3 and dentate hilus) and in the granule layer of the
      cerebellum. Increased A2R binding in DLB is consistent with expression of
      presynaptic A2R on fibers from surviving LC neurons involved in reinnervation of
      LC projection areas. These areas develop compensatory noradrenergic
      hyperinnervation in a rat model of partial LC ablation. It is also consistent
      with upregulation of post-synaptic A2R in response to loss of LC noradrenergic
      innervation. Either mechanism could lower the threshold for increased agitation
      in response to noradrenergic outflow in these dementing disorders.

PMID- 11445256
TI  - The hemochromatosis gene affects the age of onset of sporadic Alzheimer's
      disease.
AB  - In the present study we analysed the genotype of HFE, the gene involved in
      hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age
      matched non-demented controls. We observed that patients carrying the mutant HFE
      H63D allele had a mean age at onset of 71.7 +/- 6.0 years versus 76.6 +/- 5.8
      years of those who were homozygous for the wild-type allele (p = 0.001). The
      frequency of the HFE-H63D mutation was highest (0.22) in the patients aged <70
      years at the time of disease onset, whereas it was 0.12 in those with disease
      onset at an age of 70-80 years, and 0.04 in those aged more than 80 years. The
      APOE genotype did not significantly modify the effect of HFE on age at onset. We
      conclude that mild disturbances of iron homeostasis associated with a common
      genetic determinant may interact with other pathogenic mechanisms involved in AD.
      HFE mutations may anticipate AD clinical presentation in susceptible individuals.

PMID- 11445257
TI  - No association between DLST gene and Alzheimer's disease or Wernicke-Korsakoff
      syndrome.
AB  - Among many candidate genes for the genetically heterogeneous Alzheimer's disease
      (AD), only apolipoprotein E (ApoE) has been confirmed. Another candidate is the
      dihydrolipoyl succinyltransferase (DLST) gene, one of three components of
      thiamine-dependent mitochondrial alpha-ketoglutarate dehydrogenase complex
      (KGDHC), because KGDHC activity is reported reduced in AD patients. Also
      characterized by reduced KGDHC activity is another neuropsychiatric disease,
      Wernicke-Korsakoff syndrome (WKS), which results from thiamine deficiency.
      Examination of specific DLST gene polymorphism in 247 Japanese AD patients, 53
      alcoholic WKS patients, and 368 nondemented Japanese control subjects revealed no
      significant differences in DLST genotypes and failed to replicate the findings of
      earlier studies indicating an association between DLST gene polymorphism and AD.

PMID- 11445258
TI  - Incidence of dementia: does gender make a difference?
AB  - Several studies suggested that women are at higher risk of dementia than men.
      However, that was based on rather limited data. We investigated possible gender
      differences in the incidence of dementia, Alzheimer's disease and vascular
      dementia, in the Rotterdam Study, a large population based prospective cohort
      study in the Netherlands of 7,046 persons aged 55 years and older, free of
      dementia at baseline. In 40,441 person-years of follow-up (mean 5.7 years) we
      identified 395 new cases of dementia (overall incidence: 9.8 per 1,000 person
      years). Alzheimer's disease was the most frequent subtype of dementia (293 cases;
      7.2 per 1,000). Vascular dementia was diagnosed in 57 participants (1.5 per
      1,000). Overall, dementia incidence was similar for men and women (rate ratio
      women versus men: 1.00, 95% CI: 0.80-1.24). However, after 90 years of age
      dementia incidence declined in men but not in women (rate ratio 2.61, 95% CI:
      1.04-6.56), in particular for Alzheimer's disease (rate ratio 5.79, 95% CI: 1.40
      23.90). The overall incidence of vascular dementia was lower in women than in men
      (rate ratio 0.57, 95% CI: 0.34-0.97). This large population-based study suggests
      no gender differences in the incidence of dementia up to high age. After 90 years
      of age the incidence of Alzheimer's disease is higher for women than for men. The
      incidence of vascular dementia is higher for men than for women in all age
      groups.

PMID- 11445259
TI  - Effects of age on tissues and regions of the cerebrum and cerebellum.
AB  - Normal volunteers, aged 30 to 99 years, were studied with MRI. Age was related to
      estimated volumes of: gray matter, white matter, and CSF of the cerebrum and
      cerebellum; gray matter, white matter, white matter abnormality, and CSF within
      each cerebral lobe; and gray matter of eight subcortical structures. The results
      were: 1) Age-related losses in the hippocampus were significantly accelerated
      relative to gray matter losses elsewhere in the brain. 2) Among the cerebral
      lobes, the frontal lobes were disproportionately affected by cortical volume loss
      and increased white matter abnormality. 3) Loss of cerebral and cerebellar white
      matter occurred later than, but was ultimately greater than, loss of gray matter.
      It is estimated that between the ages of 30 and 90 volume loss averages 14% in
      the cerebral cortex, 35% in the hippocampus, and 26% in the cerebral white
      matter. Separate analyses were conducted in which genetic risk associated with
      the Apolipoprotein E epsilon4 allele was either overrepresented or
      underrepresented among elderly participants. Accelerated loss of hippocampal
      volume was observed with both analyses and thus does not appear to be due to the
      presence of at-risk subjects. MR signal alterations in the tissues of older
      individuals pose challenges to the validity of current methods of tissue
      segmentation, and should be considered in the interpretation of the results.

PMID- 11445260
TI  - Age-related structural changes in the human midbrain: an MR image study.
AB  - We measured midbrain structures of 194 subjects without neurological disorders,
      using T2-weighted MR imaging. Age was negatively correlated with the maximum
      anteroposterior distance of the midbrain through the substantia nigra (MD), and
      the average distance from the substantia nigra to the red nucleus (SNRND), while
      a positive correlation was found between aging and the maximum distance of the
      substantia nigra (SND). Significant left-right differences were revealed in MD,
      SND, SNRND and the area of the red nucleus (RNA), which was possibly responsible
      for cerebral hemispheric dominance or handedness. There were gender differences
      in MD and the maximum interpeduncular distance (IPD) in age-matched groups. Age
      related structural changes of the midbrain may have a close relation to a decline
      in motor performance with aging. These findings provide essential information to
      evaluate the MR images of neurodegenerative disorders.

PMID- 11445261
TI  - Sex differences in corpus callosum size: relationship to age and intracranial
      size.
AB  - This quantitative MRI study reports measurement of corpus callosum area taken
      from midsagittal brain images in 51 healthy men and 41 healthy women, spanning
      the adult age range (22 to 71 years). Men had larger brains and corpora callosa
      than women, but callosal size did not correlate with age in either sex.
      Intracranial (i.c.) volume (ICV) and midsagittal i.c. area (ICA) of brain were
      used in covariate, regression, and ratio analyses to determine whether sex
      differences in the corpus callosum endured with statistical adjustment for sex
      differences in maximally attained brain size. With the exception of one ratio
      measure, the different statistical adjustments for the contribution of sex
      differences in brain size to corpus callosum size all indicated that men had
      larger corpora callosa than women for their brain size. A subsample of men and
      women selected to be matched on i.c. volume and age confirmed this statistical
      observation. Sexual dimorphism in the corpus callosum is not a simple artifact of
      sex differences in brain size and may reflect differences in connectivity
      necessitated by differences in brain size.

PMID- 11445262
TI  - Influence of diet restriction on NMDA receptor subunits and learning during
      aging.
AB  - This study was designed to determine if changes related to aging and diet in the
      mRNA expression of subunits of the NMDA receptor were associated with changes in
      binding to NMDA receptors and learning ability in C57Bl/6 mice. Three age groups
      (3, 15, and 26-27 months old) and 2 diet groups (ad libitum-fed and diet
      restricted) were used. The old ad libitum-fed mice had significantly poorer
      performance in a spatial reference memory task than all other groups. Diet
      restriction slightly spared glutamate binding to NMDA sites and improved zeta1,
      but not epsilon2, mRNA expression. Significant correlations were found between
      NMDA-displaceable [(3)H]glutamate binding and both learning ability and epsilon2
      and epsilon1 mRNA density in several brain regions. Learning ability in the old
      mice also correlated with the ratios of mRNA expression for epsilon1 and epsilon2
      and/or zeta1 subunits in the parietal cortex and CA1 region of the hippocampus.
      This suggests that it is the relationship between subunit expression levels that
      is important for maintaining memory functions in older animals.

PMID- 11445263
TI  - Effects of age and dietary antioxidants on cerebral electron transport chain
      activity.
AB  - Aging is a pleiotropic process involving genetic and environmental factors.
      Recently it has been demonstrated that dietary constituents may affect
      senescence. In the present study, adult (3 month-old) mice were fed diets
      supplemented with ubiquinone (coenzyme Q(10)), alpha-lipoic acid, melatonin or
      alpha-tocopherol for a six-month period to determine if antioxidants may reverse
      or inhibit the progression of certain age-associated changes in cerebral
      mitochondrial electron transport chain (ETS) enzyme activities. The control
      consisted of a group of mice maintained on a basal diet for the same period. The
      activity of cytochrome c oxidase (Complex IV) increased with age but melatonin
      supplementation restored the activity to levels of 3 month-old animals. The
      activity of succinate dehydrogenase (Complex II) showed no age-related changes.
      However, this enzyme complex was elevated, in animals supplemented with coenzyme
      Q(10), alpha-lipoic acid and alpha-tocopherol, above corresponding values
      obtained with basal diet. NADH-ubiquinone oxidoreductase (Complex I) and
      ubiquinol:ferricytochrome-c oxidoreductase (Complex III) activities remained
      unchanged.

PMID- 11445264
TI  - Mitochondrial DNA deletions parallel age-linked decline in rat sensory nerve
      function.
AB  - In rats, the function of sensory nerves in the hind limb declines significantly
      with age. Normally aging rats and rats treated neonatally with capsaicin were
      studied here. Quantification of vascular response and substance P in young (3
      months) and old (24 months) rats showed additive effects of age and capsaicin
      treatment. The levels in dorsal root ganglion of a particular deletion in
      mitochondrial DNA (mtDNA(4834)) were about 300-fold higher in old compared to
      young rats. Capsaicin treatment had no significant effect on mtDNA(4834)
      abundance. Dorsal root ganglia of old (but not young) rats were found to contain
      a spectrum of multiple deletions. The abundance of mtDNA(4834) in dorsal root
      ganglia from individual rats correlated strongly with their decline in vascular
      function, even where vascular responses were systematically depressed due to
      prior capsaicin treatment. One possibility is that mitochondrial DNA mutations
      directly lead to functional decline at mitochondrial and tissue levels.
      Alternatively, loss of mitochondrial DNA integrity and physiological decline may
      be consequences of the same factor, such as oxidative stress.

PMID- 11445265
TI  - Does cerebral activity change in middle-aged adults in a visual discrimination
      task?
AB  - The purpose of this study was to assess changes in cerebral activity in middle
      aged adults (MA: 50 years) compared to young adults (YA: 20 years). Subjects had
      to compare the duration or the intensity of a visual stimulus with a previously
      memorized standard. Evoked potentials were recorded, and a dipole model (obtained
      from PET data on young adults) was applied for fitting late-latency components.
      MA performance was poorer than YA performance. Task-specific ERP late components
      were found (P3 in intensity, CNV in duration), but P3 had a lower amplitude and
      CNV was less frontal in MAs compared to YAs. The activity of the dipoles that
      generate late components - cuneus in the intensity task, right frontal in the
      duration task, and anterior cingulate in both tasks-was less ample or less peaked
      in MAs than in YAs. This study characterizes neurobiological effects of aging
      that may already be visible during midlife.

PMID- 11445266
TI  - Age-related changes in striatal function of freely-moving F344 rats.
AB  - Multi-wire electrode arrays were used to record extracellular
      electrophysiological activity in striatal medium spiny-like neurons of freely
      moving young (6-8 months) and aged (24-26 months) Fischer 344 rats. While overall
      basal firing rates did not differ between the two groups, d-amphetamine (5.0
      mg/kg) increased firing rates more in the young rats. D-Amphetamine had
      heterogeneous effects on firing rates, however, exciting 63% of the neurons while
      inhibiting 37%. Neurons were classified according to their response to d
      amphetamine (excited vs. inhibited) to examine age-related differences in firing
      rates and bursting activity. In the d-amphetamine-excited neurons, pre-drug
      intraburst firing rates were higher in the old rats. This effect was reversed by
      d-amphetamine. D-Amphetamine increased the percentage of spikes within bursts to
      a greater extent in the aged animals and decreased burst durations greater in the
      young group. In d-amphetamine-inhibited neurons, firing rates were diminished in
      the old rats more than they were in the young rats. These results demonstrate age
      related alterations in striatal electrophysiological activity that may help
      explain motor deficits seen in senescence.

PMID- 11445267
TI  - Regional transport of TNF-alpha across the blood-brain barrier in young ICR and
      young and aged SAMP8 mice.
AB  - The blood-brain barrier (BBB) controls the exchange of regulatory substances,
      including tumor necrosis factor-alpha (TNF), between the brain and the blood.
      Transport across the BBB of some regulatory substances is altered with aging.
      Here, we measured the blood to brain unidirectional influx rate (Ki) for whole
      brain and 10 brain regions for radioactively labeled TNF in three groups of mice:
      young (2 mo old) ICR (the standard outbred albino laboratory mouse also termed CD
      1), young SAMP8 (a strain which develops impaired learning and memory with aging
      that correlates with an age-related increase in brain levels of amyloid beta
      protein), and aged (17 mo) SAMP8 mice. In ICR mice, the hypothalamus had the
      fastest (1.73 microl/g-min) and the parietal cortex the slowest (0.189 microl/g
      min) rates of uptake, a regional difference of about 9 fold. No differences in
      transport into whole brain or brain regions occurred between the ICR and young
      SAMP8, showing a lack of differences between strains. Transport was higher for
      the occipital cortex, midbrain, and striatum in aged SAMP8 mice. These results
      show blood-borne TNF enters some regions of the brain much more readily than
      others and TNF transport is increased into some brain regions of the SAMP8 mice
      at an age when learning and memory are impaired.

PMID- 11445268
TI  - Expression of stress proteins alpha B-crystallin, ubiquitin, and hsp27 in pallido
      nigral spheroids of aged rhesus monkeys.
AB  - Ubiquitin and alpha B-crystallin belong to a class of proteins which are
      overexpressed in a variety of human neuropathological conditions associated with
      increased cellular stress. In this study we have examined the brains of aged
      rhesus monkeys (Macaca mulatta; n = 10, mean age: 29.7 years) using antibodies
      against the stress proteins ubiquitin, alpha B-crystallin, and heat shock protein
      27 (hsp27). Here, we demonstrate an increased expression of ubiquitin, alpha B
      crystallin, and hsp27 in spheroid bodies predominantly localized in the globus
      pallidus and pars reticulata of the substantia nigra. A portion of the pallido
      nigral spheroids also contained ferric iron as highlighted by Perls' staining. On
      the basis of these findings we advance the hypothesis that expression of
      ubiquitin, alpha B-crystallin, and hsp27 in pallido-nigral spheroids of aged
      rhesus monkeys represents a stress response possibly related to increased iron
      mediated oxidative stress.

PMID- 11445269
TI  - Memory performance in healthy elderly without Alzheimer's disease: effects of
      time and apolipoprotein-E.
AB  - Transgenic mice expressing human APOE-epsilon4 develop an age-dependent decline
      in memory without pathological features of Alzheimer's disease (AD). This
      implicates APOE in the maintenance of memory during normal senescence, but
      parallel human studies are limited because longitudinal investigations of memory
      usually do not exclude patients with AD or "questionable" AD (QD). The current
      study examined the effect of APOE on cognitive function over time in elderly
      without dementia. We hypothesized that, compared to other APOE alleles memory
      decline even in healthy elderly would be greater among those with an APOE
      epsilon4. The results of neuropsychological tests, grouped into domains of
      memory, language and visuospatial/cognitive function by factor analysis, were
      examined at three intervals over a seven-year period in 563 healthy elderly
      without AD or QD using generalized estimating equations. Memory performance
      declined over time, while scores on the visuospatial/cognitive and language
      factors did not change. Increased age was associated with lower scores, and
      higher education with higher scores on all factors at each interval. No APOE
      allele was associated with performance on a specific cognitive factor at any
      interval, but the presence of an APOE-epsilon4 allele was associated with a more
      rapid decline in the memory factor over the follow-up period. The effect was most
      pronounced among individuals with less than 10 years of formal education. There
      was no similar time-dependent relationship between APOE-epsilon4 and the language
      or visuospatial/cognitive factors. Transgenic mice and elderly humans without AD
      or QD expressing APOE-epsilon4 show a decline in memory performance over time.
      These observations provide evidence for an APOE-specific effect on memory during
      senescence.

PMID- 11445270
TI  - Neuroretinal function is normal in early dementia of the Alzheimer type.
AB  - We recently demonstrated that retinal ganglion cell function, optic nerve head
      parameters and the retinal nerve fiber layer thickness are not altered in early
      dementia of the Alzheimer type (DAT). Our current objective was to assess whether
      the function of cells located more distally in the retina is also unaffected by
      the disease. We evaluated 23 individuals with early to moderate DAT and 23
      healthy age-matched subjects, all displaying clinically normal visual function.
      Scotopic and photopic flash electroretinograms (fERGs) and oscillatory potentials
      (OPs) were recorded. The amplitude and latency of the retinal potentials did not
      differ between DAT and control subjects. Our current results showing normal fERGs
      and OPs in early DAT indicate that the underlying neurons giving rise to these
      signals are not impaired by the disease process. These data support and extend
      our recent findings suggesting that visual deficits in DAT do not stem from
      neuroretinal dysfunction.

PMID- 11445271
TI  - Nerve growth factor rescue of cisplatin neurotoxicity is mediated through the
      high affinity receptor: studies in PC12 cells and p75 null mouse dorsal root
      ganglia.
AB  - Nerve growth factor (NGF) rescues dorsal root ganglion neurons and PC12 cells
      from cisplatin-induced cell death. Two model systems were used to demonstrate
      that rescue is mediated through the high affinity NGF receptor. In dorsal root
      ganglion (DRG) neurons isolated from p75(-/-) and control mice, 20 ng/ml NGF
      completely prevented cisplatin-induced death. In PC12 cells, we overexpressed
      receptor chimeras between the tumor necrosis factor and NGF receptors. We
      demonstrated that activation of the intracellular domain of Trk A is responsible
      for the NGF rescue effect.

PMID- 11445272
TI  - Histamine N-methyltransferase regulates histamine-induced phosphoinositide
      hydrolysis in guinea pig cerebellum.
AB  - We report here that the dose-response curve of the histamine-stimulated
      phosphoinositide hydrolysis in the guinea pig cerebellar slices was shifted to
      the left when the slices were pretreated with SKF 91488 (100 microM), a specific
      inhibitor of histamine N-methyltransferase (HMT). In contrast, the pretreatment
      of the cerebellar slices with aminoguanidine (100 microM - 1 mM), an inhibitor of
      diamine oxidase, had no effect on histamine-induced phosphoinositide hydrolysis.
      HMT mRNA was expressed abundantly in cerebellum, especially in Purkinje cells.
      These observations suggest that HMT regulates histaminergic neurotransmission in
      guinea pig cerebellum more predominantly than diamine oxidase in histamine
      degradation.

PMID- 11445273
TI  - Cerebrovascular melatonin MT1-receptor alterations in patients with Alzheimer's
      disease.
AB  - The pineal hormone melatonin has two major functions: as a transducer of the
      circadian day-night signal across the seasons, and as a vasoactive substance
      regulating cerebral circulation. The vasoconstrictive effects of melatonin have
      been postulated to be mediated by the melatonin 1a-receptor (MT1). The objective
      of this study was to provide the first immunohistochemical evidence for the
      localization of vascular MT1 in human control hippocampus compared to Alzheimer's
      disease (AD) patients, since regional blood flow impairments contribute to the
      neurodegenerative course of the disease. Both superficial and intrahippocampal
      arteries revealed MT1 immunoreactivity in adventitia in controls, which was
      distinctly increased in AD patients. The increased MT1 in AD may indicate a
      regulatory response to impaired melatonin levels in those patients, contributing
      to the regulation of cerebral circulation.

PMID- 11445274
TI  - Peripheral inflammation reduces the response of spinal dorsal horn neurons to an
      NK3 receptor agonist.
AB  - The neurokinin receptors NK1 and NK3 are involved in processing nociceptive
      information in the spinal dorsal horn and in central changes following persistent
      peripheral injury. However, little is known about functional changes in these
      receptor systems, particularly the NK3 receptor. We have performed intracellular
      recordings from spinal dorsal horn neurons in vitro, using spinal cords obtained
      both from control rats and from those with a peripheral inflammation induced by
      carrageenan. Application of the NK1 receptor agonist, [Sar(9),
      Met(O2)(11)]Substance P and the NK3 receptor agonist, Senktide, produced slow,
      long lasting depolarizations. The Senktide- but not [Sar(9),
      Met(O2)(11)]Substance P-induced depolarizations were significantly smaller in
      carrageenan-treated rats. These data indicate an altered role for the NK3
      receptor in the spinal dorsal horn following acute peripheral inflammation.

PMID- 11445275
TI  - Lack of the involvement of mu1-opioid receptor subtype on motivational effects
      induced by the endogenous mu-opioid receptor ligands endomorphin-1 and -2 in the
      mouse.
AB  - The present study was designed to investigate the role of mu-opioid receptor
      subtypes in the motivational effect of endogenous mu-opioid receptor ligands,
      endomorphin-1 and -2. In C57BL/6J mice, endomorphin-1 produced a significant
      place preference, whereas endomorphin-2 exhibited a significant place aversion.
      These effects were abolished by a mu1/mu2-opioid receptor antagonist beta
      funaltrexamine. Under these conditions, both endomorphin-1 and -2 produced their
      motivational effects in mu1-opioid receptor-deficient CXBK mice, indicating the
      mu2-opioid receptor involvement. Furthermore, in the lower midbrain including
      ventral tegmental area, both endomorphin-1 and -2 equally produced dose-related
      increases in guanosine-5'-o-(3-[35S] thio) triphosphate bindings in C57BL/6J and
      CXBK mice. These findings indicate that endomorphin-1 and -2 may produce distinct
      motivational effects via respective mu2-opioid receptor isoforms in the mouse.
      Furthermore, endomorphin-1 and -2 produced the mu1-resistant G-protein activation
      in the mouse lower midbtrain.

PMID- 11445276
TI  - Dopamine D5 receptor gene polymorphism and the risk of levodopa-induced motor
      fluctuations in patients with Parkinson's disease.
AB  - Motor fluctuations are the most common complication of levodopa therapy for
      Parkinson's disease (PD). Genetic factors could play a role in determining the
      occurrence of motor fluctuations. To investigate whether dopamine receptor D5
      (DRD5) T978C polymorphism is associated with the risk of developing motor
      fluctuations in PD, we studied this polymorphism in a case-control study of 120
      subjects with sporadic PD and 110 control subjects. We found that the overall
      allelic and genotypic frequencies did not differ significantly between patients
      with PD and control subjects (all P>0.7), and between motor fluctuators (n=50)
      and non-motor fluctuators (n=50) (all P>0.8). It suggests that DRD5 T978C
      polymorphism is not associated with the susceptibility to PD, nor with the risk
      of developing motor fluctuations in PD. Therefore, other polymorphisms that alter
      the expression of the dopamine receptors should be further studied.

PMID- 11445277
TI  - Caffeine inhibits exercise-induced increase in tryptophan hydroxylase expression
      in dorsal and median raphe of Sprague-Dawley rats.
AB  - Effect of caffeine on the expression of tryptophan hydroxylase (TPH), rate
      limiting enzyme of serotonin synthesis, in dorsal and median raphe was
      investigated via immunohistochemistry. In exercise groups, Sprague-Dawley rats
      were put on treadmill running for 30 min per day for 6 consecutive days. On the
      seventh day, animals of control-with-caffeine group were injected subcutaneously
      with 4 mg/kg caffeine, while control-without-caffeine group were injected with
      0.9% NaCl, sacrificed 2 h later. Exercise-with-caffeine group and exercise
      without-caffeine group were injected with caffeine and NaCl, respectively; all
      out time was determined 1 h after injection, and then sacrificed. Caffeine
      increased all-out time in exercised rats, and inhibited the exercise-induced
      elevation in TPH expression. The suppressive effect of caffeine on TPH expression
      in exercised rats can be suggested as one possible ergogenic mechanism of
      caffeine.

PMID- 11445278
TI  - The mRNA level of the potassium-chloride cotransporter KCC2 covaries with seizure
      susceptibility in inferior colliculus of the post-ischemic audiogenic seizure
      prone rat.
AB  - Cardiac arrest and resuscitation were used to induce brain damage and
      susceptibility to sound-triggered seizures in Sprague-Dawley rats. Glucose
      preloading was used to vary seizure susceptibility. Because loop diuretics can
      block these seizures, we investigated changes in KCC2, a potassium-chloride
      cotransporter, in the inferior colliculus - the origin of the seizures. Using
      polymerase chain reaction (PCR), we found that collicular KCC2 mRNA levels
      covaried with seizure susceptibility in these animals. Using quantitative PCR, we
      found that a fivefold increase in collicular KCC2 mRNA levels was associated with
      a doubling of seizure incidence. A hypothesis linking KCC2 activity to seizure
      susceptibility is presented.

PMID- 11445279
TI  - Event-related brain potentials to sound omissions differ in musicians and non
      musicians.
AB  - The mismatch negativity (MMN) component of the auditory event-related brain
      potential reflects the automatic detection of sound change. MMN to occasionally
      omitted sounds in a tone series can be used to investigate the time course of
      temporal integration in the acoustic system. We used MMN to study differences in
      temporal integration in musicians and non-musicians. In experiment 1,
      occasionally omitted 'sounds' in an otherwise regular tone series evoked a
      reliable MMN at interstimulus intervals (SOAs) of 100, 120, 180 and 220 ms in
      musicians. In non-musicians, MMN was smaller/absent in the 180 and 220 ms SOAs,
      respectively. In experiment 2, deviance of a tone was induced by presenting tones
      at a shorter SOA (100 or 130 ms) compared to the standard stimulus (150 ms).
      Musicians showed a reliable MMN for both deviant SOAs whereas non-musicians
      showed an MMN only for tones presented 50 ms prior to a standard tone (SOA 100
      ms). These results indicate that the temporal window of integration seems to be
      longer and more precise in musicians compared to musical laypersons and that long
      term training is reflected in changes in neural activity.

PMID- 11445280
TI  - Pairing of forskolin and KCl increases differentiation of immortalized
      hippocampal neurons in a CREB Serine 133 phosphorylation-dependent and
      extracellular-regulated protein kinase-independent manner.
AB  - Although cAMP response element binding protein (CREB)- and extracellular
      regulated protein kinase (ERK)-mediated pathways have been linked to each other
      in neuronal differentiation, involvement of these in hippocampal neuronal cell
      line has not been defined. Using an immortalized hippocampal cell line, HiB5, we
      have tried a pairing of forskolin with KCl depolarization, which acts as an ERK
      and CREB kinase activator in hippocampal neurons, to investigate if an activation
      of ERK and phosphorylation of CREB at the critical regulatory site, serine 133
      might be coupled in differentiation. Differentiation toward a neuronal phenotype
      was synergistically and markedly increased by the pairing of forskolin and KCl
      depolarization. The synergistic effect was accompanied by an increase in
      phosphorylation of CREB Ser-133, but not phosphorylation of ERK, and was not
      inhibited by MEK inhibitor, PD98059. These findings indicate that phosphorylation
      of the transcriptional factor CREB may function to facilitate differentiation of
      HiB5 cells.

PMID- 11445281
TI  - Pertussis toxin-induced hyperacute autoimmune encephalomyelitis in Lewis rats is
      correlated with increased expression of inducible nitric oxide synthase and tumor
      necrosis factor alpha.
AB  - The involvement of inducible nitric oxide synthase (iNOS) and tumor necrosis
      factor alpha (TNF-alpha), which have diverse roles in the progression of
      autoimmune disease models, was studied in pertussis toxin (PT)-induced hyperacute
      experimental autoimmune encephalomyelitis (EAE) in Lewis rats. The expression of
      TNF-alpha mRNA (increased 5-fold, P<0.01) and iNOS protein (3-fold, P<0.01) was
      much greater in the spinal cords with PT(+) EAE at the peak stage of EAE than in
      those with PT(-) EAE, as shown by competitive PCR and Western blot analysis,
      respectively. Immunohistochemistry showed that the majority of ED1-positive
      macrophages in EAE lesions contained iNOS, and that there were many more iNOS
      positive cells in the CNS lesions of PT(+) rats than in those of PT(-) rats.
      These findings suggest that PT-induced hyperacute EAE is partly mediated by the
      enhanced expression of iNOS and TNF-alpha in the early stages of rat EAE.

PMID- 11445282
TI  - Transferrin C2 variant does not confer a risk for Alzheimer's disease in Koreans.
AB  - We analyzed the transferrin (TF) and apolipoprotein E (APOE) genotypes of 164
      probable Alzheimer's disease (AD) patients and 239 cognitively normal elderly
      controls in Koreans. We failed to detect a significant difference in genotypic
      frequencies and allelic frequencies of the TF polymorphism between the AD group
      and control group (P>0.1 by Chi square test). The frequency of the TF C2 variant
      did not differ by the diagnosis when the APOE epsilon4-positive subjects and APOE
      epsilon4-negative subjects were analyzed separately (P>0.1 by Chi square test).
      The TF C2 variant did not influence the age-at-onset of AD independently or
      synergistically with the occurrence of the APOE epsilon4 allele (P>0.1 by ANOVA).
      The TF C2 variant did not confer a risk for AD in Koreans.

PMID- 11445283
TI  - Fastigiovestibular projections in the rat: retrograde tracing coupled with
      gammaamino-butyric acid and glutamate immunohistochemistry.
AB  - In this study, a double labeling technique using retrograde tracing with protein
      gold complex (gold-HRP) in conjunction with a gammaamino-butyric acid (GABA) and
      glutamate immunohistochemical procedure was performed to identify GABA (GABA-IR)
      and glutamate (Glu-IR) immunoreactive neurons in the cerebellar fastigial nucleus
      (FN) that projects to the vestibular nuclei (VN). The results show that FN
      neurons projecting to the VN consist of both GABA-IR and Glu-IR neurons with a
      predominance of glutamatergic ones. Because GABAergic neurons in the cerebellar
      nuclei project to the inferior olive (IO), double retrograde labeling experiments
      were performed with injections of gold-HRP in the IO and of biotilynated dextran
      amine in the VN. This showed that the GABA-IR fastigiovestibular neurons project
      by axon collaterals to both the VN and the IO.

PMID- 11445284
TI  - Decrease of methionine and S-adenosylmethionine and increase of homocysteine in
      treated patients with Parkinson's disease.
AB  - Levodopa is administered with dopa decarboxylase inhibitors (DDI) to prevent its
      peripheral degradation. This increases conversion of levodopa to 3-O-methyldopa
      (3-OMD) by catechol-O-methyltransferase (COMT). S-adenosylmethionine (SAM), which
      is synthesized from adenosine triphosphate and methionine (MET), serves as methyl
      donor for this O-metabolisation of levodopa with resulting conversion of SAM to
      total homocysteine (tHcy) via S-adenosylhomocysteine (SAH). Previous studies
      showed augmented plasma levels of tHcy in long-term levodopa/DDI-treated patients
      with Parkinson's disease (PP). Objective of this study was to compare MET, SAM,
      levodopa, 3-OMD, tHcy and SAH in plasma of 20 levodopa/DDI treated PP and
      corresponding controls. A significant decrease of MET respectively SAM and an
      increase of tHcy appeared in PP. SAH with its short half-life did not differ.
      Levodopa/DDI long-term treatment contributes to altered levels of substrates of
      the O-methylation cycle in PP.

PMID- 11445285
TI  - Age- and sex-related expression of norbin in the brain cortex of mice.
AB  - Norbin is a novel neuron specific protein that extends the neurites of neuronal
      cells. It is expressed in neural tissues like brain cortex, hippocampus, spinal
      cord and cerebellum. In this paper, we have studied the expression of norbin mRNA
      and protein in the brain cortex of male and female mice of different ages.
      Northern blot analysis showed that the level of norbin mRNA increased in both
      sexes during aging. However, Western blotting revealed that the protein increased
      in male but decreased in female with advancing age. These findings suggest that
      norbin is involved in brain function which is dependent on age and sex.

PMID- 11445286
TI  - Losing the error related negativity in the EEG of human subjects: an indicator
      for willed action.
AB  - When people make errors in a discrimination task, a negative-going waveform can
      be observed in scalp-recorded EEG that has been coined the error-related
      negativity (ERN). We hypothesized that the ERN only occurs with slips, that is
      unwilled action errors, but not if an error is committed willingly and
      intentionally. We investigated the occurrence of the ERN in a choice reaction
      time task that has been shown to produce an ERN and in an error simulation task
      where subjects had to fake errors while the EEG was recorded. We observed a loss
      of the ERN when errors were committed in willed actions but not in unwilled
      actions thus supporting the idea that the production of the ERN is tied to slips
      in unwilled actions but not mistakes in willed actions.

PMID- 11445287
TI  - Preattentive voice discrimination by the human brain as indexed by the mismatch
      negativity.
AB  - The goal of the present study was to determine whether the mismatch negativity
      (MMN), a component of the auditory event-related potential (ERPs) indexing
      perceptual difference between any two sounds, could be used as an objective
      measure of speaker discriminability and similarity/dissimilarity. ERPs were
      recorded in response to natural speech sounds from subjects watching a silent
      video. The stimuli consisted of a sequence of repetitive 'standard' sounds (the
      vowel /e/ pronounced by a female voice), which was infrequently interspersed with
      'deviant' stimuli; the same /e/vowel pronounced by different speakers (one male
      and three females). Voice intensity and duration were matched between all the
      voices used. A separate behavioural discrimination task measured the perceptual
      distance of each deviant voice from the standard voice through pair-wise
      dissimilarity ratings. The MMN was elicited by all deviant voices. Furthermore,
      the dissimilarity ratings on the behavioural task paralleled the preattentive
      discrimination as indexed by the MMN amplitude. These results suggest that the
      MMN could be used as an objective measure of voice similarity/dissimilarity, and
      thus could serve objective speaker recognition.

PMID- 11445289
TI  - Flavonoid sequestration by the common blue butterfly Polyommatus icarus:
      quantitative intraspecific variation in relation to larval hostplant, sex and
      body size.
AB  - Common blue butterflies (Polyommatus icarus) sequester flavonoids from their
      larval food and store these pigments as part of their adult wing colouration.
      Insects were reared on 10 different diets to assess effects of host plants on
      variation in flavonoid sequestration in this moderately polyphagous butterfly.
      Rearing experiments revealed an unexpectedly large gradient in flavonoid
      richness, ranging from individuals with high flavonoid loads (reared on
      inflorescences of Medicago sativa, Trifolium repens, T. pratense) to butterflies
      which contained almost no such pigments (fed with foliage of M. sativa or Robinia
      pseudoacacia). Flavonoid sequestration was much more effective from natural
      hostplants than from experimentally offered diets which would not be accepted in
      the field. Female butterflies on average sequestered almost 60% more flavonoids
      than males. This sex difference was more pronounced on natural than on
      experimental diets. Flavonoid load was significantly and positively related to
      dry mass and forewing length as two important fitness correlates of butterflies.
      This correlation was particularly strong on experimental diets (i.e. under
      constraining conditions for development). On natural hostplants, in contrast,
      when butterflies generally were flavonoid-rich, no clear relationship between
      flavonoid load and size or mass emerged. Our analytical data are consistent with
      field results according to which females rich in UV-absorbing flavonoid wing
      pigments are more attractive to mate-searching males. In P. icarus, flavonoid
      richness might therefore increase visibility (by more effective sensory
      stimulation of the visual system), but could also confer information about the
      feeding history, and thus ontogenetically determined 'quality' of a potential
      mate.

PMID- 11445290
TI  - Phytoecdysteroids from Lamium spp: identification and distribution within plants.
AB  - Bioassay/radioimmunoassay (RIA) analysis of the seeds of four Lamium species, L.
      album, L. galeobdolon, L. maculatum and L. pupureum revealed the presence of
      phytoecdysteroids in all of them. Bioassay/RIA-guided and photo-diode array
      monitored HPLC analysis of the aerial parts of L. album and L. purpureum led to
      the isolation of four known ecdysteroids (abutasterone, inokosterone, polypodine
      B and pterosterone) from the former, and 20-hydroxyecdysone from the latter.
      Distribution and identities of ecdysteroids in different parts of these two
      species and also in the seed extract of L. maculatum have been analysed by RIA
      and bioassay.

PMID- 11445291
TI  - Phylogenetic relationships among four species of Mullidae (Perciformes) inferred
      from DNA sequences of mitochondrial cytochrome b and 16S rRNA genes.
AB  - DNA sequence comparisons of two mitochondrial DNA genes were used to infer
      phylogenetic relationships among four species of mullids. Approximately 238bp of
      the mitochondrial 16S ribosomal RNA (rRNA) and 261bp of the cytochrome b (cytb)
      genes were sequenced from representatives of three mullid genera (Mullus,
      Upeneus, Pseudopeneus), present in the Mediterranean Sea. Trees were constructed
      using three methods: maximum likelihood (ML), neighbor joining (NJ) and parsimony
      (MP). The results of the analyses of these data together with published data of
      the same mtDNA segments of two other perciform species (Sparus aurata, Perca
      fluviatilis), support the previous taxonomic classification of the three genera
      examined, as well as the classification of the two red mullet species in the same
      genus.

PMID- 11445292
TI  - Differential expression for tissue-specific isozymes in three species of
      Hypostomus Lacepede, 1803 (Teleostei: Loricariidae).
AB  - The expression patterns of 14 enzymatic systems in skeletal muscle, liver and
      heart tissues of three species of Hypostomus from the Iguacu River basin (Brazil)
      were investigated. Although the patterns were similar for the three species,
      different tissues showed differential expressions, and the data showed that
      differential tissue expressions of isoperoxidases may be due to preferential
      combination or association of polypeptide subunits. The detected patterns for SOD
      isozymes showed that the quaternary structures of these enzymes were in
      disagreement with the subunit number reported for the majority of other
      vertebrate groups. Tissue-specific restriction on heterotetramer formation also
      were described in LDH and MDHP isozymes. Thus, these tissue-specific gene
      expression character in the species of Hypostomus have the greatest potential to
      be recognized and applied in systematic studies among species of Hypostomus.

PMID- 11445293
TI  - Phytoecdysteroids in seeds of Lloydia serotina (Liliaceae).
AB  - Seeds of a number of species in the Liliaceae (sensu Brummitt, 1992) were
      examined for the presence of ecdysteroid agonist and antagonist activities. No
      species were antagonistic to 20-hydroxyecdysone action on the ecdysteroid
      responsive Drosophila melanogaster B(II) cell line and only one extract, that of
      Lloydia serotina, was agonistic. This activity is attributable to the presence of
      phytoecdysteroids as detected by ecdysteroid-specific radioimmunoassay and the
      agonist version of the B(II) bioassay. HPLC in conjunction with radioimmunoassay
      and bioassay have been used to determine the ecdysteroid profile. The major
      ecdysteroids present are identified as 20-hydroxyecdysone and polypodine B
      (5beta,20-dihydroxyecdysone).

PMID- 11445294
TI  - The role of lipophilic and polar flavonoids in the classification of temperate
      members of the Anthemideae.
AB  - Lipophilic and vacuolar flavonoids were separately identified in representative
      temperate species of the genera Anthemis, Chrysanthemum, Cotula, Ismelia,
      Leucanthemum and Tripleurospermum. The four Anthemis species investigated
      variously produced four main surface constituents, in leaf and flower: santin,
      quercetagetin 3,6,3'-trimethyl ether, scutellarein 6,4'-dimethyl ether and 6
      hydroxyluteolin 6,3'-dimethyl ether. By contrast, surface extracts of disc and
      ray florets of the species of Chrysanthemum, Cotula, Ismelia, Leucanthemum and
      Tripleurospermum surveyed yielded five common flavones in the free state:
      apigenin, luteolin, acacetin, apigenin 7-methyl ether and chrysoeriol. Polar
      flavonoids were isolated and identified in leaf, ray floret and disc floret of
      all the above plants. Anthemis species were distinctive in having flavonol
      glycosides in the leaves, whereas the leaf flavonoids of the other taxa were
      generally flavone O-glycosides. The 3-glucoside and 3-rutinoside of patuletin
      were characterised for the first time from Anthemis tinctoria ssp. subtinctoria.
      Two new flavonol glycosides, the 5-glucuronides of quercetin and kaempferol, were
      obtained from the leaf of Leucanthemum vulgare, where they co-occur with the
      related 5-glucosides and with several flavone glycosides. The ray florets of
      these Anthemideae generally contain apigenin and/or luteolin 7-glucoside and 7
      glucuronide, whereas disc florets have additional flavonol glycosides, notably
      the 7-glucosides of quercetin and patuletin and the 7-glucuronide of quercetin. A
      comparison of the flavonoid pattern encountered here with those previously
      recorded for Tanacetum indicate some chemical affinity between Anthemis and
      Tanacetum. Flavonoid patterns of the other five genera are more distinct from
      those of Tanacetum and suggest that those genera form a related group. All 14
      species surveyed for their flavonoid profiles have distinctive constituents and
      the chemical data are in harmony with modern taxonomic treatments of the
      "Chrysanthemum complex" as a series of separate genera.

PMID- 11445295
TI  - Flavonoids as chemotaxonomic markers for Asteraceae.
AB  - Flavonoids have been shown to be good taxonomic markers for Asteraceae. More than
      800 compounds comprising 4700 flavonoid occurrences were included in a
      computational system specially made for chemotaxonomic purposes. Some
      implications of flavonols, flavones and other types as well as structural
      features of them are discussed for tribes and subtribes of Asteraceae.

PMID- 11445296
TI  - Constituents of three Icelandic Alchemilla species.

PMID- 11445297
TI  - 3-Methoxyflavones and a novel coumarin from Psiadia dentata.

PMID- 11445299
TI  - Acyclic diterpenes and sterols from the genera Bifurcaria and Bifurcariopsis
      (Cystoseiraceae, Phaeophyceae).

PMID- 11445298
TI  - Sesquiterpene lactones from Centaurea tweediei.
AB  - Aerial parts of Centaurea tweediei from Argentina afforded as the main
      constituent the sesquiterpene lactone onopordopicrin and minor amounts of a new
      heliangolide, a new guaianolide, a new eudesmanolide, a new eudesmane acid and
      the lignans arctigenin and matairesinol.

PMID- 11445300
TI  - Proceedings and abstracts of The Fifth International Meeting on Recent Advances
      in MR Applications to Porous Media. Bologna, Italy, 9-11 October 2000.

PMID- 11445302
TI  - The relationship of problems in biomedical MRI to the study of porous media.
AB  - The NMR methods that are used to characterize inanimate porous media measure
      relaxation times and related phenomena and material transport, fluid displacement
      and flow. Biological tissues are comprised of multiple small, fluid-filled
      compartments, such as cells, that restrict the movement of the bulk solvent water
      and whose constituents influence water proton relaxation times via numerous
      interactions with macromolecular surfaces. Several of the methods and concepts
      that have been developed in one field of application are also of great value in
      the other, and it may be expected that technical developments that have been
      spurred by biomedical applications of MR imaging will be used in the continuing
      study of porous media. Some recent specific studies from our laboratory include
      the development of multiple quantum coherence methods for studies of ordered
      water in anisotropic macromolecular assemblies, studies of the degree of
      restriction of water diffusion in cellular systems, multiple selective inversion
      imaging to depict the ratios of proton pool sizes and rates of magnetization
      transfer between proton populations, and diffusion tensor imaging to depict
      tissue anisotropies. These illustrate how approaches to obtain structural
      information from biological media are also relevant to porous media. For example,
      the recent development of oscillating gradient spin echo techniques (OGSE), an
      approach that extends our ability to resolve apparent diffusion changes over
      different time scales in tissues, has also been used to compute surface to volume
      measurements in assemblies of pores. Each of the new methods can be adapted to
      provide spatially resolved quantitative measurements of properties of interest,
      and these can be efficiently acquired with good accuracy using fast imaging
      methods such as echo planar imaging. The community of NMR scientists focused on
      applications to porous media should remain in close communication with those who
      use MRI to study problems in biomedicine, to their mutual benefits.

PMID- 11445303
TI  - Time-dependent velocities in porous media dispersive flow.
AB  - Pulsed Gradient Spin Echo (PGSE) NMR methods may be used to measure the
      asymptotic dispersion coefficient as well as the velocity autocorrelation
      function (VACF) in porous media flow. The VACF can be measured in the frequency
      domain using repetitive gradient pulse trains, and in the time domain using
      double PGSE encoding. The one dimensional double PGSE method, and the two
      dimensional velocity exchange experiment (VEXSY) are briefly outlined and their
      application to flow in monodisperse 0.5 mm diameter beads packs described, both
      axial and transverse VACFs being examined. The measured correlation times are
      shown to agree well with calculated values. The asymptotic dispersion
      coefficients agree with literature values in the case of transverse flow while in
      axial flow it is shown that asymptotic conditions are not achieved, even for
      observation times longer than the correlation time for flow around a bead.

PMID- 11445304
TI  - "Shining light" on NMR and MRI in porous materials.

PMID- 11445305
TI  - Characterization of partially sintered ceramic powder compacts using fluorinated
      gas NMR imaging.
AB  - We use nuclear magnetic resonance (NMR) imaging of C2F6 gas to characterize
      porosity, mean pore size, and permeability of partially sintered ceramic (Y-TZP
      Yttria-stabilized tetragonal-zirconia polycrystal) samples. Conventional
      measurements of these parameters gave porosity values from 0.18 to 0.4, mean pore
      sizes from 10 nm to 40 nm, and permeability from 4 nm(2) to 25 nm(2). The NMR
      methods are based on relaxation time measurements (T(1)) and the time dependent
      diffusion coefficient D(Delta). The relaxation time of C2F6 gas is longer in
      pores than in bulk gas and it increases as the pore sizes decrease. NMR yielded
      accurate porosity values after correcting for surface adsorption effects. A model
      for T(1) dependence on pore size that accounts for collisions between gas
      molecules and walls as well as surface adsorption effects is proposed. The model
      fits the experimental data well. Finally, the long time limit of D(Delta)/D(o),
      where D(o) is the bulk gas diffusion coefficient is useful for measuring
      tortuosity, while the short time limit was not achieved experimentally and could
      not be used for calculating surface-area to volume (S/V) ratios.

PMID- 11445306
TI  - Characterization of porous media structure by non linear NMR methods.
AB  - In this paper we discuss the possibility of modifying the multiple spin echoes
      existing theory, developed for a homogeneous system, to describe also an
      inhomogeneous system such as a porous medium. We report here the first
      experimental application of MSE methods to materials like travertine. The ratio
      A(2)/A(1) from water in travertine presents minima for characteristic values of
      the delay time tau, like what was previously observed in the trabecular bone. By
      a judicious choice of the delay time tau and of the G gradient strength, the MSE
      sequence can be made sensitive to a specific length-scale of the sample
      heterogeneity. Furthermore the MSE image shows a particular new contrast that
      makes the non linear NMR method very attractive for the assessment of variations
      of the porous structure in porous systems.

PMID- 11445307
TI  - Relationships between flow and NMR relaxation of fluids in porous solids.
AB  - Measurements are presented which correlate the displacements, X(Delta),
      determined by PGSE NMR, with the multi-mode transverse 1H NMR relaxation of water
      flowing through a glass bead pack, for which the dominant relaxation mechanism is
      diffusion through inhomogeneous internal magnetic fields. Analytical solution for
      the joint amplitude A[X(Delta), T(2k)] for the case of laminar flow in a circular
      pipe, with a diffusion-to-surface mechanism, shows that, for other than the
      lowest mode (k = 0), the contributions to the observed relaxation for a given
      X(Delta) may involve negative as well as positive amplitudes. The experimental
      measurements are shown to agree with this general conclusion, showing clear
      evidence of the presence of relaxation modes with negative amplitude at larger
      values of X(Delta). It is shown that in these, or similar measurements, which
      provide a spatially-resolved view of surface-mediated relaxation, allowance must
      be made for fitting with both positive and negative amplitudes.

PMID- 11445308
TI  - Stochastic effects on single phase fluid flow in porous media.
AB  - The flow encoded PEPI technique has been used to measure the fluid velocity
      distribution and fluid flow of water passing through a phantom comprising
      randomly distributed 10 mm glass beads. The object of these experiments is to
      determine the degree of causality between one steady-state flow condition and
      another. That is to say, knowing the mean fluid velocity and velocity
      distribution, can one predict what happens at a higher mean fluid velocity? In a
      second related experiment flow is established at a given mean fluid velocity. The
      velocity distribution is measured. The flow is then turned off and later re
      established. In both kinds of experiment we conclude that the errors in
      predicting the flow velocity distribution and the errors in re-establishing a
      given velocity distribution lie well outside the intrinsic thermal noise
      associated with velocity measurement. It follows, therefore, that the causal
      approach to prediction of flow velocity distributions in porous media using the
      Navier-Stokes approach is invalid.

PMID- 11445309
TI  - Magnetic resonance visualisation of single- and two-phase flow in porous media.
AB  - Three-dimensional MRI and flow visualisation data are presented for single and
      two-phase flow occurring within packed beds of glass spheres. The initial
      motivation for this work has been to understand the operation of fixed-bed
      reactors used in many chemical processing operations; these systems also serve as
      model porous media in which to investigate the effect of the structure of a pore
      space on the flow phenomena occurring within it. For the case of single-phase
      flow, maps of the liquid shear rate components are calculated from which forces
      on individual spheres within the bed are obtained. The velocity histogram for
      flow transverse to the direction of superficial flow is exponential in both
      negative and positive directions. This form of the velocity histogram implies an
      exponential form for the displacement propagator, in contrast to the Gaussian
      distribution obtained by pulsed gradient spin echo measurements. This difference
      arises because the spatially resolved velocity imaging sequence measures only the
      average velocity within each voxel and is insensitive to the effects of
      incoherent (diffusive) motion. Visualisations of air-water flow through a sphere
      pack are also reported and the capability of MRI to yield information on rivulet
      formation and surface wetting characteristics is illustrated.

PMID- 11445310
TI  - Tortuosity measurement and the effects of finite pulse widths on xenon gas
      diffusion NMR studies of porous media.
AB  - We have extended the utility of NMR as a technique to probe porous media
      structure over length scales of approximately 100-2000 microm by using the spin
      1/2 noble gas 129Xe imbibed into the system's pore space. Such length scales are
      much greater than can be probed with NMR diffusion studies of water-saturated
      porous media. We utilized Pulsed Gradient Spin Echo NMR measurements of the time
      dependent diffusion coefficient, D(t), of the xenon gas filling the pore space to
      study further the measurements of both the pore surface-area-to-volume ratio,
      S/V(p), and the tortuosity (pore connectivity) of the medium. In uniform-size
      glass bead packs, we observed D(t) decreasing with increasing t, reaching an
      observed asymptote of approximately 0.62-0.65D(0), that could be measured over
      diffusion distances extending over multiple bead diameters. Measurements of
      D(t)/D(0) at differing gas pressures showed this tortuosity limit was not
      affected by changing the characteristic diffusion length of the spins during the
      diffusion encoding gradient pulse. This was not the case at the short time limit,
      where D(t)/D(0) was noticeably affected by the gas pressure in the sample.
      Increasing the gas pressure, and hence reducing D(0) and the diffusion during the
      gradient pulse served to reduce the previously observed deviation of D(t)/D(0)
      from the S/V(p) relation. The Pade approximation is used to interpolate between
      the long and short time limits in D(t). While the short time D(t) points lay
      above the interpolation line in the case of small beads, due to diffusion during
      the gradient pulse on the order of the pore size, it was also noted that the
      experimental D(t) data fell below the Pade line in the case of large beads, most
      likely due to finite size effects.

PMID- 11445311
TI  - Flow, diffusion, and thermal convection in percolation clusters: NMR experiments
      and numerical FEM/FVM simulations.
AB  - Percolation objects were fabricated based on computer-generated, two- or three
      dimensional templates. Random-site, semi-continuous swiss cheese, and semi
      continuous inverse swiss-cheese percolation models above the percolation
      threshold were considered. The water-filled pore space was investigated by NMR
      imaging and, in the presence of a pressure gradient, NMR velocity mapping. The
      fractal dimension, the correlation length, and the percolation probability were
      evaluated both from the computer-generated templates and the corresponding NMR
      spin density maps. Based on velocity maps, the percolation backbones were
      determined. The fractal dimension of the backbones turned out to be smaller than
      that of the complete cluster. As a further relation of interest, the volume
      averaged velocity was calculated as a function of the probe volume radius. In a
      certain scaling window, the resulting dependence can be represented by a power
      law the exponent of which was not yet considered in the theoretical literature.
      The experimental results favorably compare to computer simulations based on the
      finite-element method (FEM) or the finite-volume method (FVM). Percolation theory
      suggests a relationship between the anomalous diffusion exponent and the fractal
      dimension of the cluster, i.e., between a dynamic and a structural parameter. We
      examined interdiffusion between two compartments initially filled with H2O and
      D2O, respectively, by proton imaging. The results confirm the theoretical
      expectation. As a third transport mechanism, thermal convection in percolation
      clusters of different porosities was studied with the aid of NMR velocity
      mapping. The velocity distribution is related to the convection roll size
      distribution. Corresponding histograms consist of a power law part representing
      localized rolls, and a high-velocity cut-off for cluster-spanning rolls. The
      maximum velocity as a function of the porosity clearly visualizes the percolation
      transition.

PMID- 11445312
TI  - Surface dynamics of liquids in porous media.
AB  - We report remarkable differences in the 1H nuclear magnetic relaxation dispersion
      data (NMRD) between water and other common aprotic solvents such as acetone when
      in contact with high surface area calibrated microporous chromatographic silica
      glasses that contain trace paramagnetic impurities located at or close to the
      pore surface. All these differences have been related to the particular chemical
      behaviors and dynamics of these liquids at the pore surface. We apply this
      technique to probe the structure and dynamics of water and oil at the surface of
      calibrated macroporous systems, where similar surface dynamics effects have been
      observed. This technique is also applied to follow the first hydration stage of a
      white cement-paste. Last, we present an analysis of the magnetic field dependence
      of 1H nuclear relaxation data to exhibit the microporosity of ultra high
      performance concretes.

PMID- 11445313
TI  - The modulation of coupled relaxation in porous media.
AB  - This work investigates the effects of modulation of the transverse and
      longitudinal relaxation of the surface-fluid/pore-fluid spin system in porous
      media. Important new NMR well logging applications identify pore fluids by
      varying the CPMG T(2) pulse spacing to discriminate on the basis of fluid
      diffusivities in applied and local static magnetic field gradients. However,
      anomalous laboratory CPMG T(2) results have been reported repeatedly over 25
      years for various porous media filled with a single fluid. In relatively large
      pores, at near bulk conditions, the transverse relaxation of diffusing molecular
      spins should be proportional to the square of the CPMG pulse spacing tau, the
      susceptibility contrast at the pore wall and the applied gradient. Observed is a
      markedly linear tau dependence that saturates at a plateau for large tau. The
      effect is not quadratic in applied gradient or susceptibility. For large pores,
      the tau dependence and the saturation value are proportional to the surface-to
      volume ratio of the pores. This is in distinct contrast to the behavior observed
      by Borgia, Brown and Fantazzini for systems with much smaller pores at higher
      magnetic fields. The large-pore anomalous behaviors can be explained as a
      modulation of the exchange between surface-fluid and pore-fluid spins, such as
      observed by Luz and Meiboom in 1963 for water enriched with quadrupolar 17O.
      Scalar coupling of the solid-surface spins to the fluid-surface spins was
      postulated by Kleinberg, Kenyon and Mitra as a dominant relaxation mechanism for
      the surface fluid. The CPMG tau effect can be described as the modulation of the
      exchange coupling by the CPMG pi pulses, which mix the magnetizations between the
      exchanging, strongly coupled spin systems of the pore-fluid and the surface
      fluid, which is, in turn, weakly coupled by scalar or pseudo-scalar interactions
      to the fast-relaxing solid surface.

PMID- 11445314
TI  - Optimization of timing in the Carr-Purcell-Meiboom-Gill sequence.
AB  - The Carr-Purcell-Meiboom-Gill sequence is widely used in grossly inhomogeneous
      fields to characterize fluid saturated porous media. The distribution of T(2)
      relaxation times is a measure of the distribution of pore sizes. We present here
      a theoretical analysis of the spin dynamics of this sequence in strongly
      inhomogeneous fields. Based on this analysis, we optimize the timing of the
      sequence for maximal signal bandwidth. It is shown that the initial pulse spacing
      should be decreased by a time 2t(90)/pi. Experimental results in a strayfield set
      up confirm the theoretical analysis. The optimized timing increases the measured
      signal bandwidth and increases the ratio of signal-to-noise by 1.2 dB without
      affecting the measured relaxation time.

PMID- 11445315
TI  - Direct measurement of porous media local hydrodynamical permeability using gas
      MRI.
AB  - The concept of hydraulic permeability is at the core of modeling single phase or
      multi-phase flow in heterogeneous porous media, as it is the spatial distribution
      of the permeability that primarily governs the behavior of fluid flow in the
      medium. To date, the modeling of fluid flow in porous media has been hampered by
      poor estimates of local permeability. Magnetic Resonance Imaging is well known
      for its ability to measure non-invasively the local density and flow rate of
      different fluids saturating porous media [1,2]. In this paper we demonstrate the
      first non-invasive method for the direct measurement of a single projection of
      the local permeability tensor of a porous medium using gas-phase MRI. The
      potential for three-dimensional imaging of the medium permeability is also
      discussed. The limitations of the method are listed and results are presented in
      a model porous medium as well as in a real oil reservoir rock.

PMID- 11445316
TI  - Multi-gradient pulse investigations of fluid transport in porous media.
AB  - NMR pulsed field gradient (PFG) experiments employing the application of n
      gradient pulses k(1) ellipsis k(n) are discussed in a general way as an n-fold
      encoding of position at successive times. The experiments are then represented by
      a sampling of n-dimensional k-space, K(n). Various parameters of motion can be
      derived from the evolution of correlations within the n-dimensional position (r
      )space, R(n), which is the Fourier conjugate space to K(n). A wide class of NMR
      experiments may be described by this formalism, where the dimension of the
      experiment is often reduced by imposing conditions to the free variables. This is
      demonstrated for the case of displacement measurements where the condition
      summation operatork(i) = 0 is met. The two simplest pulse sequences which allow
      one to correlate displacements at two different times with each other are
      presented. While the three-pulse version of SERPENT encodes displacements in two
      interleaved time intervals Delta(1) and Delta(2), the four-pulse VEXSY experiment
      includes a mixing time tau(m) in between both encoding intervals Delta. The
      behaviour of fluid transport subject to external pressure through a model porous
      system is demonstrated by means of numerical simulations of SERPENT and VEXSY
      experiments for water flowing through a packed bed of monosized spherical
      particles. Displacements parallel (Z) and perpendicular (X) to the main flow
      direction are determined and the 2-D joint probability densities and the
      conditional probabilities are discussed along with the correlation coefficients
      related to the displacements at different encoding times. It is shown that all
      possible correlations between Z and X(2) in VEXSY decay with time constants
      comparable to the average time needed for a fluid molecule to cover one bead
      diameter, while a negative correlation is observed between transverse (X)
      displacements which is explained by molecules flowing along streamlines which
      follow the circumference of the spherical particles. Correlations for
      displacements during the different times in SERPENT generally decay much slower
      and provide complementary information about the evolution of displacements with
      time.

PMID- 11445317
TI  - NMR diffusion of hyperpolarised 3He in aerogel: a systematic pressure study.
AB  - Diffusion of hyperpolarised 3He in a silica aerogel sample with 98% porosity was
      measured by NMR, and systematically studied as a function of pressure P in the
      range 20 mbar -1 bar. Spin-echo amplitudes, recorded with pulsed gradients in the
      usual CMPG sequence, follow a monoexponential decay, and the decay rate varies
      quadratically with the gradient intensity: thus the apparent diffusion
      coefficient of the gas D can be evaluated. Our results show a power-law (1/D
      proportional to P(0.55)), which could be consistent with a fairly broad mean free
      path distribution, implying some inhomogeneity in the aerogel structure. We have
      observed a spatial non-uniformity of D, and some deviation to the quadratic
      dependence of the decay rate with the gradient intensity, possibly related to
      sample structure inhomogeneity.

PMID- 11445318
TI  - An evaluation of NMR cryoporometry, density measurement and neutron scattering
      methods of pore characterisation.
AB  - Sol-gel silicas with nominal pore diameters ranging from 25A to 500A were studied
      by NMR cryoporometry, and by neutron diffraction and small angle scattering from
      dry silicas over the Q range 8. 10(-4)A(-1) < or = Q < or = 17A(-1). Density and
      imbibation experiments were also performed. Geometric models of porous systems
      were constructed and were studied by both analytic techniques and Monte-Carlo
      integration. These models, combined with the information from the above
      measurements, enabled the calculation of the fully density corrected solid-solid
      density correlation functions G(r) for the sol-gel silicas, deduction of the
      (voidless) silica matrix density, measurement of the silica fraction in the grain
      and of the packing fraction of the silica grains and an estimation of the water
      equivalent residual hydrogen on the dried silica surface. In addition, the pore
      diameter D, pore diameter to lattice spacing ratio D/a, and pore and lattice
      variance sigma could also be measured. While the NMR cryoporometry pore diameter
      measurements for the sol-gel silicas show excellent co-linearity with the nominal
      pore diameters as measured by gas adsorption, and the calculated pore diameters
      from the measured neutron scattering show surprisingly good agreement with these
      measurements at large pore diameters, there is a divergence between the
      calibrations for pore diameters below about 100A.

PMID- 11445319
TI  - Surface effects and dipolar correlations of confined and constrained liquids
      investigated by NMR relaxation experiments and computer simulations.
AB  - Local order and molecular dynamics of liquids near surfaces strongly deviate from
      the behavior in the bulk. This in particular refers to liquid crystals above the
      bulk isotropization temperature. Transverse relaxation data of 5CB examined in
      porous glasses with different pore sizes are reported. A strong pore size effect
      was found. For the interpretation, a simple diffusion-adsorption computer
      simulation was carried out. Molecules can diffuse from the isotropic bulk part of
      the pore fluid to the ordered surface layer and vice versa. The residual dipolar
      correlation function is characterized by a slowly decaying tail owing to repeated
      returns of molecules to the surface. At each return the molecular orientation
      correlation is recovered as far as the surface sites visited have orientations
      correlated to the initial site. That is, molecular orientation is controlled by
      the "reorientation mediated by translational displacement" process considered in
      previous papers.

PMID- 11445320
TI  - Characterisation of crosslinked elastomeric materials by 1H NMR relaxation time
      distributions.
AB  - One of the most critical structural parameters in elastomeric materials is the
      density of cross-linking between the polymeric chains. This chemical feature
      greatly affects chain motions and is determinant in controlling mechanical
      properties of the final product. NMR techniques are widely and efficiently
      applied to investigation of such materials. In this study we have measured both
      transverse and longitudinal 1H relaxation times of a series of polybutadiene
      rubber samples with increasing crosslink density induced by chemical treatment.
      This approach allowed the observation of T(1) and T(2) decrease with the increase
      of crosslink density in the samples examined. The data obtained have been
      analyzed and compared to theoretical models.

PMID- 11445321
TI  - Probing pores using elementary quantum mechanics.
AB  - The relaxation of polarized spins in a porous medium has been utilized as a probe
      of its structure. We note that the governing diffusion problem has a close
      parallel to that of a particle in a box, an elementary Quantum mechanics toy
      model. Following the spirits of "free electron" model, we use generic properties
      of the eigen spectrum to understand features common to a wide variety of pore
      geometry, consistent with large scale numerical simulations and experimental
      data.

PMID- 11445322
TI  - Pore sizes and pore connectivity in rocks using the effect of internal field.
AB  - A novel nuclear magnetic resonance method has been applied to several sandstone
      rocks to measure the pore size distribution using the magnetization decay due to
      diffusion in the internal magnetic field (DDIF). By comparing the results of the
      DDIF and Hg porosimetry experiments, a clear picture of pore connectivity
      emerges. The pore body diameter can be defined using the DDIF data and is found
      to have a clear trend as a function of porosity.

PMID- 11445323
TI  - SPIRAL-SPRITE: a rapid single point MRI technique for application to porous
      media.
AB  - This study presents the application of a new, rapid, single point MRI technique
      which samples k space with spiral trajectories. The general principles of the
      technique are outlined along with application to porous concrete samples, solid
      pharmaceutical tablets and gas phase imaging. Each sample was chosen to highlight
      specific features of the method.

PMID- 11445324
TI  - Study of molecular mobility of fluid in zeolite NaX.
AB  - The self-diffusion of n-decane in zeolite NaX was studied by NMR PFG method. The
      situation when the liquid was only in the crystalline channels was studied in
      details. The restricted molecular motion of liquid in the crystalline channels
      was observed. The reasons of the anomalous self-diffusion of n-decane in zeolite
      bed were stated. The technique of the determination of the genuine self-diffusion
      coefficient in such porous systems was proposed. The genuine self-diffusion
      coefficients for system NaX/n-decane were obtained.

PMID- 11445325
TI  - Surface-induced order and diffusion in 5CB liquid crystal confined to porous
      glass.
AB  - Liquid crystals confined into small cavities are known to have a weak
      orientational order even above the nematic-isotropic transition temperature. The
      surface-induced order and molecular dynamics in this temperature range are
      studied with the aid of deuteron NMR spectra, spin relaxation times T(1) and
      T(2,) proton dipolar-correlation effect, and direct measurements of the effective
      diffusion coefficient for the liquid crystal 5CB confined to controlled-pore
      glasses. Our results show that an arrangement of molecules parallel to the wall
      is induced by local molecular interactions between the liquid crystal and solid,
      resulting in a weak and temperature independent surface order parameter, S(0)
      approximately 0.02 +/- 0.01. There is no indication of a significant slowing-down
      of molecular diffusion at the wall, neither rotational nor translational. In
      cavities of nanometer size, where the nematic order evolves gradually upon
      cooling, a broadening of the NMR linewidths due to dynamic effects should be
      taken into account.

PMID- 11445326
TI  - Magnetic susceptibility contrast induced field gradients in porous media.
AB  - Using a two-component composite theory, we compute the internal field gradient of
      a periodic porous medium induced by the magnetic susceptibility contrasts. The
      magnetization of such a system is computed by using the diffusion eigenstates in
      Fourier representation. We show that the volume averaged field gradient, when
      used in the formula for free diffusion, significantly overestimates the
      magnetization decay rate. We also establish bounds for such a periodic system
      within which the Gaussian approximation is valid for diffusion of spins in the
      pore space.

PMID- 11445327
TI  - NMR T2 distributions and two phase flow simulations from x-ray micro-tomography
      images of sandstones.
AB  - The distribution of fluids in the pore space of a series of sandstones is
      calculated as a function of capillary pressure using a two phase flow simulation
      model. The pore space is represented by a system of channels and nodes which are
      derived from x-ray micro-tomography images of sandstones. The sandstones studied
      varied in permeability from approximately 40 to 3,000 mD. The simulation results
      illustrate the significance of the pore level by-pass phenomena in controlling
      the location of fluids within the pore structure. The implications of these
      results on the interpretation of NMR T(2) distributions to determine the
      irreducible water saturation are discussed.

PMID- 11445328
TI  - NMR diffusometry of oil-in-water emulsions.
AB  - The diffusion propagator of the continuous aqueous phase of concentrated oil-in
      water emulsions is used to probe the relationship between emulsion microstructure
      and bulk rheological properties. This is done by expanding the stimulated echo
      amplitude, S(q,Delta), as a multiple exponential time series expansion in Delta,
      with wavevector dependent expansion coefficients. These coefficients are compared
      with predictions from several theoretical models for three types of stable
      emulsion, each differing in microstructure. Empiric relationships between the
      wavevector expansion coefficients and bulk rheology are established.

PMID- 11445329
TI  - Using NMR displacement imaging to characterize electroosmotic flow in porous
      media.
AB  - Pulsed field gradient nuclear magnetic resonance (PFG-NMR) and NMR imaging were
      used to study temporal and spatial domains of an electrokinetically-driven mobile
      phase through open and packed segments of capillaries. Characteristics like
      velocity distribution and an asymptotic dispersion are contrasted to viscous flow
      behavior. We show that electroosmotic flow in microchannel geometries can offer a
      significant performance advantage over the pressure-driven flows at comparable
      Peclet numbers, indicating that velocity extremes in the pore space of open tubes
      and packed beds are drastically reduced. An inherent problem of capillary
      electrochromatography that we finally address is the existence of wall effects
      when in the general case the surface zeta-potentials of the capillary inner wall
      and the adsorbent particles are different. Using dynamic NMR microscopy we were
      able resolve this systematic velocity inequality of the flow pattern which
      strongly influences axial dispersion and may be responsible for long time-tails
      of velocity distribution in the mobile phase.

PMID- 11445330
TI  - Electrophoretic NMR studies of electrical transport in fluid-filled porous
      systems.
AB  - An NMR technique is described which allows the observation of ionic charge
      carriers moving in the electric field within a porous system saturated with
      electrolyte solution. This method, which was recently developed in our
      laboratory, gives experimental access to the study of electric transport in
      disordered media on a microscopic level and offers new potential for morphology
      studies. We performed 1H NMR PFG self-diffusion measurements on ions combined
      with ionic drift velocity measurements by electrophoretic NMR (ENMR), each as a
      function of observation time Delta. In this way we obtained time-dependent self
      diffusion coefficients D(+/-) (Delta) and time-dependent electric mobilities
      mu(+/-) (Delta) of polyatomic cations and anions in porous media. The porous
      media used were gels and glass bead packs. From the behaviour of D(+/-) (Delta)
      and mu(+/-) (Delta) at long observation times the tortuosities T(p) (D(+/-)) and
      T(p) (mu(+/-)) are derived, allowing a direct experimental check of the validity
      of the Einstein relation (D(+/-) is proportional to mu(+/-)) in a disordered
      medium. The tortuosities obtained via the diffusivity of ions are compared with
      those obtained via the diffusivity of water molecules. We also make a first
      attempt to derive the specific surface S/V(p) from the time-dependence of the
      ionic mobility at short observation times and discuss possible advantages of
      those measurements in morphology studies of porous media.

PMID- 11445331
TI  - Time domain analysis: an alternative way to interpret PGSE experiment.
AB  - We report a theoretical development which aims at interpreting Pulsed Gradient
      Spin Echo data for diffusing fluids in saturated porous media. It consists in
      analyzing the time dependence of PGSE amplitudes for each single gradient
      strength, and introduces a new diffusion coefficient D(q) as being continuously
      dependent on the length scale in the material. Both experimental measurements on
      water saturated bead packings and simulated experiments in 2D and 3D model
      systems are interpreted with this approach. D(q) is shown to give a new insight
      in the micro-macro transition. Its evolution vs. the length scale is non trivial,
      and can be sensitive to local slow kinetic effects.

PMID- 11445332
TI  - Low-frequency velocity correlation spectrum of fluid in a porous media by
      modulated gradient spin echo.
AB  - In addition to the fast correlation for local stochastic motion, the molecular
      velocity correlation function in a fluid enclosed within the pore boundaries
      features a slow long time-tail decay. Here we present its study by the NMR
      modulated gradient spin-echo method (MGSE) [1] on a system of water trapped in
      the space between the closely packed polystyrene beads. With MGSE pulse sequence,
      a repetitive train of RF pulses with interspersed gradient pulses periodically
      modulates the spin phase. It gives the spin echo attenuation proportional to a
      value of the molecular velocity correlation spectrum at the modulation frequency.
      Covering the frequency range between Hz and MHz, it is a complement to the quasi
      elastic neutron scattering, and so a suitable technique for the investigation of
      low frequency molecular dynamics in fluids. In our experiment, it enables to
      extract the low frequency correlation spectrum of water molecules confined in
      porous media. The function exhibits a negative long time-tail characteristic (a
      low frequency decay of the spectrum), which can be interpreted as a molecular
      back scattering on boundaries. The results can be well fitted with the spectrum
      calculated from the solution of the Langevin equation for restricted diffusion
      (which exhibits an exponential decay) [2] as well as with the spectrum obtained
      when simulating the hydrodynamics of molecular motion constrained by capillary
      walls (which gives an algebraic decay) [3]. Despite much work on theories and
      simulation, which predict slow negative long time tail of molecular velocity
      correlation dynamics in confined fluids, the obtained velocity correlation
      spectrum is the first experimental evidence to confirm these effects. The
      obtained dependence of spin echo attenuation on time, gradient strength and
      modulation frequency is also the first experimental verification of the recently
      developed approach to the spin echo in porous media, that uses the spin phase
      average with the cumulant expansion to get the attenuation as a discord of spin
      spatial coherence [4].

PMID- 11445333
TI  - Examples of marginal resolution of NMR relaxation peaks using UPEN and
      diagnostics.
AB  - The multiexponential inversion program UPEN by the authors [J. Magn. Reson. 1998;
      132: 65-77; Ibid. 2000;147:273-85] employs negative feedback to a regularization
      penalty to implement variable smoothing when both sharp and broad features appear
      on a single distribution of relaxation times. This allows a good fit to
      relaxation data that correspond to a sum of decaying exponentials plus random
      noise, but it usually does not give a good fit to data that are distorted by
      systematic errors from instrument problems, which can cause erroneous
      "resolution" or erroneous non-resolution of peaks. UPEN provides a series of
      diagnostic parameters to help identify such data problems that can lead to
      interpretation errors, and, in particular, to warn when a close call on the
      resolution or non-resolution of nearby peaks might be questionable. Examples are
      given from a series of T(2) data sets from desiccated bone samples, with examples
      where the presence of two peaks is required by good data, examples where the
      presence of two peaks is negated by good data, and examples where the resolution
      or non-resolution of peaks cannot be trusted because of instrumental distortions
      revealed by UPEN diagnostic parameters. It is suggested that processing
      relaxation data with UPEN in nearly real time could permit retaking data while a
      sample is still available if the diagnostic parameters show instrumental
      problems.

PMID- 11445334
TI  - From porous media to trabecular bone relaxation analysis: spatial variation of
      marrow 1H relaxation time distributions detected in vitro by quasi-continuous
      distribution analysis.
AB  - Quasi-continuous distributions of T(1) and T(2) of 1H nuclei were analyzed in
      vitro at 20MHz on some twenty fresh bone samples of pig femur. Large numbers of
      data points allowed a detailed investigation. Relaxation data were inverted by
      UPEN (Uniform PENalty inversion). In all samples the widths of the distributions,
      covering more than two decades, are not even close to being compatible with
      single exponential components. Moreover, the T(1) and T(2) distributions show
      enough character to distinguish the samples. We observe a spatial variation of
      these characteristics and in particular a second peak centered at 500-600 ms
      appearing in some proximal femur samples. The quasi-continuous distribution
      allows one to correlate the water content of the sample with parts of the
      distributions in specific time ranges. The signal fraction with T(1) values
      longer than a cutoff time of about 170 ms is in very good agreement with the
      water content of the samples and is significantly larger in the group of samples
      cored from proximal femur. Also T(2) distributions differentiate the samples, and
      the signal fraction with T(2) shorter than about 30 ms is significantly larger in
      the group of distal femur samples.

PMID- 11445335
TI  - Combined MR-relaxation and MR-cryoporometry in the study of bone microstructure.
AB  - MR-Relaxation (MRR) of 1H nuclei and MR-Cryoporometry (MRC) are combined to
      assess their feasibility and their potential in the study of bone microstructure.
      In principle, both techniques are able to give information on the structure of
      the pore space confining the fluids. Cow femur samples were carefully cored and
      cleaned in order to remove the natural fluids inside. For MRR analysis quasi
      continuous distributions of T(1) and T(2) were obtained on samples fully
      saturated with water. Cyclohexane was used as a saturating fluid for MRC
      analysis. All T(1) and T(2) quasi-continuous distributions of water confined in
      bone samples are more than three decades wide, showing sufficient details to
      differentiate the samples. Pore size distributions obtained by MRC also
      differentiate the samples showing different characteristics of the pore space
      structure in the range of the highest sensitivity of the method (typically 3 to
      100 nm, mesopore range). In particular, in samples where MRR shows a large
      fraction of signal with relaxation times below 10(2) ms, MRC indicates a large
      fraction of pore volume with pore sizes in the mesopore range.

PMID- 11445336
TI  - Short-TE projection reconstruction NMR microscopy of trabecular bone.
AB  - The aim of this study was to assess the potential of projection reconstruction
      (PR) NMR microscopy in the quantitative evaluation of trabecular bone
      architecture. Short-TE PR spin-echo microimages were acquired at 7.05 T on normal
      bone explants. The main structural parameters such as bone volume fraction (BVF),
      trabecular thickness (Tb.Th.) and trabecular separation (Tb.Sp.) were obtained
      from the 3D microimages using the method of directed secants. Quantitative
      structural data were then compared with those derived from conventional spin-echo
      microimages. Our study indicates that projection reconstruction NMR microscopy
      promises to be more accurate than the conventional FTI method in the analysis of
      trabecular bone.

PMID- 11445337
TI  - A novel application of NMR microscopy: measurement of water diffusion inside
      bioadhesive bonds.
AB  - The self-diffusion coefficient of water (D) inside bioadhesive bonds formed by
      dry and prehydrated hydrophilic matrices has been spatially resolved using
      nuclear magnetic resonance (NMR) microscopy. One-dimensional profiles showing the
      variation of D inside bioadhesive bonds were calculated from nine diffusion
      weighted profiles obtained immediately after bond formation and every 5 min for
      30 min. The resulting data indicated that the hydration state of a hydrophilic
      matrix can significantly and dramatically influence the dynamics of water
      movement inside a bioadhesive bond.

PMID- 11445338
TI  - Cryoporometry and relaxometry of water in silica-gels.
AB  - Both cryoporometry and relaxometry are tools to determine the pore size
      distribution (PSD) of a porous material with NMR. The melting point depression is
      described by the Gibbs-Thomson equation, yielding the PSD from cryoporometry. The
      enhanced relaxivity is caused by the surface of the porous material, yielding the
      PSD from relaxometry. The description in the classical paper of Brownstein and
      Tarr is only valid for one pore (size). The extended theory of McCall et al. is
      needed to describe a heterogeneous coupled porous system. As testing material a
      series of silica-gels called Nucleosil is chosen with typical pore sizes of 5,
      10, 12 and 30 nm. Transverse relaxation time distributions are measured using a
      CPMG-sequence for every temperature of the cryoporometry measurement. These show
      a mono exponential behaviour, indicating a strongly coupled porous structure.
      Using the cryoporometry data, an attempt is made to reproduce the averaged
      relaxivity. Agreement is found for pores with typical pore sizes between 10 nm
      and 1 microm. The model is not valid for pores smaller than 10 nm.

PMID- 11445339
TI  - Micropore size analysis in hydrated cement paste by NMR.
AB  - We present a time evolution of 1H spin-lattice relaxation rates in the laboratory
      (1/T(1)) and in the rotating frame (1/T(1rho)) of a synthetic cement paste. The
      typical results found for both rates allows us to follow the main hydration
      stages of the cement paste and the refinement of its microporosity. In particular
      the texturation of the porosity and the structuration of the surface of the
      material is evidenced.

PMID- 11445340
TI  - The NMR-MOUSE: quality control of elastomers.
AB  - New applications of the NMR-MOUSE (mobile universal surface explorer) to non
      destructive quality control of elastomers are reported. One example concern the
      thermal aging of fast clutches which was probed by measurements of 1H transverse
      relaxation time. Novel methodological developments show that 1H double-quantum
      filtered NMR signals can be generated in the inhomogeneous fields of the NMR
      MOUSE for characterization of residual dipolar couplings. This technique was
      applied to characterize reference natural rubber samples with different crosslink
      density and carbon black and silica fillers.

PMID- 11445341
TI  - Application of single point imaging (SPI) to solid state materials.
AB  - Single Point Imaging (SPI) is a 3D phase encoding MRI method proposed by S. Emid
      and J.H.N. Creyghton [1] to study solid state materials with a very short T(2)
      value (>50 micros). In this short communication experimental results of SPI
      applications to various industrial important solid materials, such as porosity of
      chocolate samples, connectivity of micro-channels in earth samples, etc. are
      reported.

PMID- 11445342
TI  - NMR hand-held moisture sensor.
AB  - An open magnet design, hand-held NMR sensor head is presented. Wood moisture
      content and cement hydration tests demonstrate the potential of the tool for in
      situ material assessment. The magnetic field distribution was adjusted by
      positioning blocks of permanent magnets using millimeter scale 3-dimensional
      magnetic field modeling. A low Q-factor circuit was used for spin-echo sequences
      with short echo times.

PMID- 11445343
TI  - Effects of hydrophobic treatments of stone on pore water studied by continuous
      distribution analysis of NMR relaxation times.
AB  - The effects of protective hydrophobic products applied to porous media such as
      stone or mortar vary greatly with the product, the porous medium, and the mode of
      application. Nuclear Magnetic Resonance (NMR) measurements on fluids in the pore
      spaces of both treated and untreated samples can give information on the contact
      of the fluid with the internal surfaces, which is affected by all the above
      factors. Continuous distributions of relaxation times T(1) and T(2) of water in
      the pores of both synthetic and natural porous media were obtained before and
      after hydrophobic treatment. The synthetic porous media are ceramic filter
      materials characterized by narrow distributions of pore dimensions and show that
      the treatment does not produce large changes in the relaxation times of the
      water. For three travertine samples most of a long relaxation time component,
      presumably from the largest pores, remains after treatment, while the amplitude
      of an intermediate component is greatly reduced. For three pudding-stone samples,
      treatment leads to a substantial loss from the long component and an even greater
      loss from the intermediate component.

PMID- 11445344
TI  - Performance evolution of hydrophobic treatments for stone conservation
      investigated by MRI.
AB  - 1H-MRI has been applied to the evaluation of the performances of a hydrophobic
      polymer (Paraloid B72), widely used for the conservation of monumental buildings
      and other stone artifacts. By this technique it has been possible to visualize
      the water diffusion in a treated rock material (Pietra di Lecce, a highly porous
      Italian biocalcarenite) and then indirectly the spatial distribution of the
      polymer in the rock. The effects of wetting-drying cycles on the hydrophobic
      efficacy of the acrylic polymer in the inner layers of the rock were also
      studied. A notable decrease in the water-repellence inside the stone was detected
      and attributed to a loss of adhesion of the polymer to the substrate, promoted by
      the action of water.

PMID- 11445345
TI  - New ways of probing surface nuclear relaxation and microdynamics of water and oil
      in porous media.
AB  - The microdynamics of water and oil in macroporous media with SiO2 or CaCO3
      surfaces has been probed at various temperatures by magnetic field-cycling
      measurements of spin-lattice relaxation rates. These measurements and an original
      theory of surface diffusion allow us to obtain surface dynamical parameters such
      as surface correlation times, residence times and diffusion coefficients. A
      coefficient of affinity of the liquids for the pore surface is deduced.

PMID- 11445346
TI  - MRI investigation of hydration and heterogeneous degradation of aliphatic
      polyesters derived from lactic and glycolic acids: a controlled drug delivery
      device.
AB  - Magnetic Resonance Imaging experiments have been used to investigate the
      degradation of drug-loaded poly(glycolic lactic acid) (PGLA) 50:50 cylinders.
      Spatial variation in the rate of degradation throughout the polymer cross-section
      has been observed non-invasively using quantitative imaging of penetrant
      concentration, T(2) and self-diffusion coefficient. This spatial variation in the
      rate of degradation was attributed to the quicker degradation in the inner region
      of the sample due to autocatalysis by carboxyl end groups generated upon ester
      bond cleavage.

PMID- 11445347
TI  - Diffusion in thin films on the surface of a porous solid.
AB  - A water-wet mono-dispersed glass bead system is saturated with two phases, a
      wetting phase of water and a non-wetting phase of tetrachloroethylene (no 1H
      signal). Pulsed field gradient NMR measurements of the one-dimensional
      probability density distribution P(Delta) (X) for the diffusive displacements of
      water molecules in times, Delta, are presented for the whole accessible water
      saturation range. At lower water contents the distributions show a distinctive
      shape, which is attributed to the distribution of the aqueous phase in thin
      surface wetting films connecting pendular rings where the beads are in contact.
      The data are reproduced well by a computer simulation of a random walk model
      based on diffusion of molecules within such a structure, allowing determination
      of the surface film thickness.

PMID- 11445348
TI  - MRI velocimetry and lattice-Boltzmann simulations of viscous flow of a Newtonian
      liquid through a dual porosity fibre array.
AB  - Viscous flow through fibrous porous media has considerable importance in a number
      of industrial processes including, in particular, resin transfer molding. In this
      paper magnetic resonance flow imaging techniques are used to visualize flow of a
      Newtonian liquid through a dual porosity structure. Of particular interest in
      these studies is the transition in the flow as the liquid moves from the open
      region into the fiber array. The ability of lattice-Boltzmann simulations to
      predict the visualized flow fields is presented and discussed.

PMID- 11445349
TI  - NMR imaging of mass transport and related phenomena in porous catalysts and
      sorbents.
AB  - NMR imaging is employed to study the preparation of supported catalysts and a
      number of mass transport processes in porous catalysts and sorbents. It is shown
      that, similar to Pt, adsorbed Pd leads to the increase of the relaxation times of
      liquids permeating porous alumina supports. A faster penetration of adsorbed
      water into the sorbent is observed when water vapor sorption by selective water
      sorbents is carried out under vacuum as compared to the sorption from moist air.
      An interruption of the capillary flow of water within the monolithic catalyst is
      shown to lead to a non-uniform drying along the monolith channels. Flow imaging
      of water inflowing into the monolith has revealed a complicated flow pattern
      characterized by the existence of counterflows in the entrance region.

PMID- 11445350
TI  - Interpretation of restricted diffusion in sandstones with internal field
      gradients.
AB  - We report on experiments to characterize internal magnetic field gradients that
      are caused by magnetic susceptibility differences between the solid phase and the
      fluids filling the pore space. Our measurements focus on low-field relaxometry of
      brine and oil in sandstones from various reservoirs around the world. Our results
      show the need to understand the dependence of internal field gradients on
      diffusion length, pore size- and fluid distribution in order to predict the
      impact of internal gradients on the interpretation of NMR experiments.

PMID- 11445351
TI  - Quantification and description of fracture network by MRI image analysis.
AB  - The contribution of fractures to total porosity and their geometrical
      descriptions have been studied by Image Analysis applied to 1H Magnetic Resonance
      Imaging (MRI). Reservoirs of different lithology were acquired with MSME 2D
      quantitative and 3D sequences. An image analysis procedure, developed ad hoc, was
      then applied to these acquisitions and the petrophysical parameters computed.
      These parameters range from fracture porosity to fracture density.

PMID- 11445352
TI  - NMR response of non-reservoir fluids in sandstone and chalk.
AB  - Transverse (T2) NMR relaxation time at 2 MHz proton resonance frequency was
      measured on core plug samples from two different lithologies, sandstone and
      chalk, before and after exposure to selected drilling fluids. The results show
      that NMR signal response was significantly altered after displacing 50% of the
      original pore fluids, crude oil and water, by drilling fluid filtrate. Relaxation
      spectra of the rock samples invaded by water-based filtrate shift to
      significantly shorter T2-values. This shift yields an underestimation of the free
      fluid volumes when selecting cut-off values of 33 ms and 100 ms for sandstone and
      chalk, respectively. In opposite, rock samples affected by oil-based filtrate
      respond with a signal indicating significantly larger free-fluid volumes than
      present before exposure. NMR-permeability calculated based on the Timur-Coates
      Free Fluid model altered in some cases by one order of magnitude.

PMID- 11445353
TI  - NMR studies of water diffusion and relaxation in hydrating slag-based
      construction materials.
AB  - The NMR relaxation properties of hydrating blast-furnace slag cements have
      recently been shown to be dominated by the effect of water self-diffusion in
      internal magnetic field gradients in the pastes. While this was suggested on the
      basis of NMR relaxometry and magnetic susceptibility data, we report here the
      results from first direct studies of the water self-diffusion in the hydrating
      paste using a specialized PFG sequence and very intensive magnetic field gradient
      pulses.

PMID- 11445354
TI  - Ion transport in porous media studied by NMR.
AB  - Moisture and salt transport in masonry can give rise to damages. Therefore a
      detailed knowledge of the moisture and salt transport is essential for
      understanding the durability of masonry. A special NMR apparatus has been made
      allowing quasi-simultaneous measurements of both moisture and Na profiles in
      porous building materials. Using this apparatus both the absorption of a 4 M NaCl
      solution in a calcium silicate brick and the drying of a 3 M NaCl capillary
      saturated fired-clay brick have been studied. It was found that during the
      absorption process the Na ions clearly stay behind, which this is caused by
      adsorption of these ions to the pore surface. For the drying it was found that at
      the beginning of the drying process the ions accumulate near the surface. As the
      drying rate decreases, diffusion becomes dominant and the ion profile levels off
      again.

PMID- 11445355
TI  - Investigation of the microporosity of high performance concrete by proton nuclear
      relaxation.
AB  - The difference in microporosity features between high and ultra high performance
      concrete was highlighted by measuring their respective proton spin-lattice
      relaxation times. A surface fractal dimension was attributed to each formulation
      and exhibits a correlation with the amount of calcium silicate hydrates.

PMID- 11445356
TI  - Measuring spatially resolved gas transport and adsorption in coal using MRI.
AB  - The storage and transport of gases in coal is of tremendous importance in the
      utilisation of coalbeds, and in particular the recovery of methane. There is also
      increasing interest in the use of coal mines as sites for carbon dioxide
      sequestration to alleviate the potentially harmful effects of global warming.
      This paper demonstrates the use of magnetic resonance imaging to investigate the
      spatiotemporal dynamics of gas transport in coal. The presence of significant
      structural heterogeneities in the coal was observed. Dynamical effects displayed
      a broad range of time constants ranging from minutes to days.

PMID- 11445357
TI  - STRAFI-NMR studies of water transport in soil.
AB  - 1-D STRAFI (STRAy FIeld) imaging is used to study water distribution in a sandy
      loam. The matric potential of the soil can be varied during acquisition of 1-D
      profiles. Results at a range of potentials are presented showing both the
      equilibrium distribution and the evolution of the profile following an abrupt
      change in matric potential. The air breakthrough point and variations in draining
      behaviour due to differences in soil compaction are identified.

PMID- 11445358
TI  - MRI as a probe of the deposition of solid fines in a porous medium.
AB  - MRI volume imaging and flow visualizations are used to investigate solid fine
      particle deposition during flow within a random packing of glass spheres. This
      process is of importance in many fields including filtration, operation of
      chemical reactors and oil recovery. Visualizations before and during deposition
      allow us to investigate how the structure of the inter-particle space and the
      properties of the fines influence the evolution of the structure and
      hydrodynamics characterizing the porous medium during deposition.

PMID- 11445417
TI  - Variation in fleece characteristics of Awassi sheep at different ages.
AB  - Fleece characteristics have economic significance in sheep. When assessing fiber
      characteristics, the importance of sex, age of sheep and the body location of the
      sample taken are important considerations. Triplicate fleece samples were
      obtained from the shoulder, right mid-side and hip of 12 male and 17 female lambs
      (6-10 months), 62 yearling ewes (14-20 months) and 235 mature ewes (28-84 months)
      by hand shearing. The greasy fleece weight, staple length, fiber length and fiber
      diameter measures were 2.1+/-0.03kg, 14+/-0.18cm, 24+/-0.26cm and 36+/
      0.33&mgr;m, respectively. Correspondingly, the medullated fibers, inner coat,
      outer coat and kemp fibers were 11.6+/-0.33, 59.7+/-0.29, 34.0+/-0.23 and 6.3+/
      0.16%, respectively. Age had a significant influence on body weight and greasy
      fleece weight, but male and females were similar. Body location of the sample had
      a significant effect on the fiber diameter, and percentages of medullated fibers,
      kemp fibers, and inner coat fibers. The finest fibers and a lower percentage of
      medullated fibers were found on the shoulder and mid-side, whereas, the
      percentage of inner coat fibers was highest on the hip. Although there was no
      significant interaction between body location and age-sex groups for fiber
      characteristics, it was important for staple and fiber length (P<0.05). The wide
      variation in fiber diameter and percentage of medullated fibers suggest potential
      for improvement of economical traits.

PMID- 11445418
TI  - Morphological variability of forestomach mucosal membrane in red deer, fallow
      deer, roe deer and mouflon.
AB  - The number and size of ruminal papillae, reticular cells and omasal laminae in
      free-living game deer (red deer, fallow deer, roe deer and mouflon) were
      examined. Mucosal membrane (MM) specimens were collected from the forestomachs of
      hunted deer. These parameters were assessed as related to the grazing
      environment, sex and age of animals. The number and size of ruminal papillae
      corresponded the best to the feeding specialization of the respective deer
      species and affecting factors. In two areas under study, the number and size of
      the ruminal papillae were significantly higher during the growing season than
      during the winter period (P<0.05) in all four species. Only the papillae on the
      dorsal wall of the rumen did not respond to seasonal changes (P>0.05).
      Differences in the number and size of papillae between different deer and mouflon
      were not significant when compared to sex, or place of origin (P>0.05). The size
      of the reticular cells and number and size of omasal laminae differed between
      individual species, but the data were not statistically significant. The
      parameters assessed in this study corresponded to the dietary choices of each
      species. The most significant differences were found between roe deer and
      mouflon. The smallest differences were found between red deer and fallow deer
      where the ruminal papillae responded to changes in the quality of the food during
      the year.

PMID- 11445419
TI  - Effects of different management practices on preweaning and early postweaning
      growth of Alpine kids.
AB  - Two sets of 40 dairy goat Alpine kids (3-9 days of age) were used to determine
      effects of group versus individual pens, preweaning access to forage and
      different milk feeding restriction regimens on preweaning and early postweaning
      growth. Treatments in the first experiment were: C1: individual pens; C2: two
      kids per pen; P: group pen; and PF: P plus free access to alfalfa hay. Treatment
      did not affect ADG gain in the 8-week preweaning phase (167, 173, 167 and 168g
      per day; S.E.=4.5) or in week 1-12 (137, 134, 149 and 128g per day for C1, C2, P
      and PF, respectively; S.E.=6.7). Treatments in the second experiment were: AL: ad
      libitum milk intake with two meals in week 3-8, then 50% of intake on the
      preceding few days with one meal in week 9-10; R-1X and R-2X: 75% of intake on
      the last few days of week 2 with one or two meals, respectively, in week 3-8,
      then, 50% intake with one meal in week 9-10; and R-2X-1X: 75% intake with two
      meals in week 3-6, then 37.5% intake with one meal in week 7-10. Milk DM intake
      in week 1-10 was greatest (P<0.05) among treatments for AL (174, 115, 128 and
      113g per day for AL, R-2X, R-1X and R-2X-1X, respectively). Starter diet DM
      intake (g per day) was 51, 78, 72 and 143 in week 7-8 (S.E.=16); 138, 194, 165
      and 249 in week 9-10 (S.E.=15); 343, 396, 388 and 417 in week 11-12 (S.E.=47);
      and 508, 530, 489 and 539 in week 13-14 (S.E.=38) for AL, R-2X, R-1X and R-2X-1X,
      respectively. ADG (g per day) was 139, 120, 119 and 131 in week 1-10 (S.E.=7) and
      105, 109, 123 and 117 in week 11-14 (S.E.=16) for AL, R-2X, R-1X and R-2X-1X,
      respectively. In conclusion, although group pens and forage access may not
      enhance ADG of artificially reared dairy goat kids by promoting early dry feed
      consumption restricted feeding regimens can yield preweaning and early
      postweaning ADG comparable to ad libitum milk intake. Also, feeding milk in
      restricted amounts once daily appears feasible, and a second reduction in milk
      intake in the latter part of the suckling phase may further stimulate dry feed
      intake.

PMID- 11445420
TI  - Dairy goat performance with different dietary concentrate levels in late
      lactation.
AB  - Alpine yearling doelings (22; 44+/-1.0kg) and mature does (25; 59+/-1.7kg) were
      used in an experiment with 16 weeks in late lactation, 8-13 weeks dry and 12
      weeks in the subsequent lactation. Diets of 20, 35, 50 or 65% concentrate and
      2.18, 2.34, 2.49 and 2.62Mcal/kg ME, respectively (20C, 35C, 50C and 65C
      treatments, respectively), were consumed ad libitum in late lactation, with a 35%
      concentrate diet (2.18Mcal/kg ME) in the first 4 weeks of the dry phase and 50%
      concentrate (2.65Mcal/kg ME) until kidding. Other goats consuming 20 or 35%
      concentrate in late lactation received 65 (2.65Mcal/kg ME) or 50% concentrate,
      respectively, in the dry phase (20A and 35A treatments, respectively). All goats
      consumed a 50% concentrate diet (2.42Mcal/kg ME) in the subsequent early
      lactation. DM intake in late lactation was similar among treatments (1.95, 2.21,
      2.17, 2.10, 1.99 and 2.00kg per day for 20C, 35C, 50C, 65C, 20A and 35A,
      respectively; S.E.=0.098) and greater (P<0.05) for does versus doelings (2.16
      versus 1.98kg per day; S.E.=0.058); DM intake in the dry phase was similar among
      treatments. Relative to BW, DM intake was greater (P<0.05) for doelings than for
      does in late lactation (4.16 versus 3.43% BW) and early lactation (4.56 versus
      3.80% BW). The effect of dietary treatment on milk production in late lactation
      varied with parity (P<0.05); milk production by doelings was 1.39, 1.49, 1.43,
      1.57, 1.29 and 1.52kg per day and by does was 1.01, 1.89, 2.38, 1.63, 1.17 and
      1.34kg per day for 20C, 35C, 50C, 65C, 20A and 35A, respectively; S.E.=0.200). BW
      change during the entire 16 weeks late lactation phase was greater (P<0.05) for
      65C than for other treatments except 50C (6.9, 5.6, 9.1, 10.4, 5.8 and 4.0kg for
      20C, 35C, 50C, 65C, 20A and 35A, respectively; S.E.=1.28), although BW at kidding
      and litter weight were similar among treatments. BW, DM intake and milk
      production in the first 12 weeks of the subsequent lactation were not affected by
      dietary treatment or parity. In conclusion, with moderate to high quality forage
      in late lactation and a moderate level of concentrate in the dry period, the
      level of concentrate fed in late lactation and in the dry period may not affect
      subsequent lactation performance regardless of parity. Milk production by
      doelings in late lactation appears relatively less responsive to dietary
      concentrate level than that by does.

PMID- 11445421
TI  - Effects of high copper supplements on performance, health, plasma copper and
      enzymes in goats.
AB  - Six growing female Nubian goats (average BW=34.8+/-0.55kg, 7-8 months of age)
      were randomly assigned to either a basal diet (BD, 10-15ppm Cu/DM), or to medium
      Cu (MC, BD+50mgCu), or to high Cu (HC, BD+100mgCu) diets for 9 weeks. This level
      would cause Cu toxicity in sheep, but none occurred in the goats. Therefore, Cu
      supplementation was then increased to 150 and 300mg per head per day, for the
      following 14 weeks; to 300 and 600mg per head per day, for the next 8 weeks; and
      to 600 and 1200mg per head per day, for an additional 4 weeks, in the MC and HC
      group, respectively. Body weight and vital signs were recorded and blood samples
      collected at different time intervals. Hematological parameters, plasma Cu,
      sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase (GOT), and gamma
      glutamyl transferase (GGT) were determined. At the termination of the study,
      tissue Cu concentration in different organs was also determined. During first 23
      weeks (<300mgCu per day) of the study there were no apparent signs of Cu
      toxicity. Cu supplementation at 600mg per head per day in young Nubian does, had
      no effect on respiration rate (RR), heart rate (HR), and decreased (P<0.05)
      rectal temperature (RT) in the HC group only. Leukocyte counts were positively
      correlated with Cu supplementation (r=+0.296, P<0.02) and negatively correlated
      (r=-0.254, P<0.05) with RT in the HC group. Plasma SDH increased (P<0.05) when Cu
      supplementation was >/=300mg per head per day, thus, SDH may serve as an early
      indicator of Cu toxicosis in goats. Increases (P<0.05) in GOT were noted when Cu
      intake was >/=600mg per head per day. Contrary to the results observed for SDH
      and GOT, feeding goats 50mgCu per day or more, resulted in an increased plasma
      GGT as compared to BD goats. Levels of SDH, GOT and GGT of the BD goats were
      within normal range. Plasma Cu was not indicative of Cu status of animals. Copper
      improved ADG by 28% at the 100-150ppm level in diet. No relationship between Cu
      intake and hair Cu was found in the present study. Highest concentration of Cu
      was found in liver, followed by duodenum, rumen and brain. Results of this study
      indicate that goats are more resistant to Cu toxicity than sheep. This is one of
      the first reports documenting significant differences in Cu requirements and
      tolerance between goats and sheep.

PMID- 11445422
TI  - Short term maintenance of sheep preantral follicles in situ in 0.9% saline and
      Braun-Collins solution.
AB  - The present study has investigated the efficiency of 0.9% saline solution and
      Braun-Collins solution in the preservation of sheep preantral follicles in situ,
      at different temperatures and different incubation periods. The ovaries were
      divided into 19 fragments for each animal. One ovarian fragment was taken
      randomly and immediately fixed for histology (control-time zero). The other 18
      ovarian fragments were randomly distributed in tubes containing 2ml of 0.9%
      saline solution or Braun-Collins solution at 4, 20 or 39 degrees C for 4, 12 or
      24h. A total of 1629, 208 and 63 primordial, primary and secondary follicles were
      examined, respectively. Histological analysis showed that the storage of ovarian
      fragments in both solutions at 20 or 39 degrees C significantly reduced the
      percentage of morphologically normal preantral follicles (MNPF) when compared
      with the control, except after preservation in 0.9% saline solution at 20 degrees
      C for 4h. In contrast, the preservation at 4 degrees C, in both solutions, kept
      the percentage of MNPF similar to control values. In conclusion, this study shows
      for the first time that sheep preantral follicles can be preserved in situ
      successfully at 4 degrees C in 0.9% saline solution or Braun-Collins solution for
      up to 24h.

PMID- 11445423
TI  - Effects of two different housing systems on behavior, physiology and milk yield
      of Comisana ewes.
AB  - Two groups of 20 early-lactating Comisana ewes were used in this study, and were
      allocated to either an indoor or outdoor daytime environment. The indoor
      environment was a 3mx12m straw bedded pen inside a pre-fabricated building. The
      outdoor environment was a 200m(2) paddock during daytime (09.00-19.00h) with ewes
      being moved to the shed, as described for the indoor treatment, at night.
      Behavior of ewes was recorded at 14 days interval from 09.00 to 19.00h. A
      phytohemagglutinin (PHA) skin test was performed at weeks 6, 11, 15 and 18 of the
      experiment to induce a non-specific delayed-type hypersensitivity in ewes.
      Jugular blood samples were taken at the beginning and at weeks 5, 10, 14 and 18
      to determine endocrine and metabolic responses of animals to housing system and
      to changes in climatic conditions and stage of lactation. Ewe milk yield was
      recorded daily and individual milk samples were analyzed for milk composition,
      coagulating properties and somatic cell count (SCC) at 14 days interval. No
      differences were found between groups for endocrine and immune responses. Outdoor
      ewes had increased locomotor activities (P<0.01) and decreased idling (P<0.05)
      compared to indoor animals. The outdoor group had higher levels of blood
      creatinine (P<0.01) and inorganic phosphorus (P<0.05) as well as lower urea
      (P<0.01) and glucose (P<0.001) concentrations compared to the indoor group. Milk
      yield and composition were not changed by the housing system, though significant
      timextreatment interactions were found for milk constituents, with indoor-housed
      ewes having higher (P<0.05) milk protein, fat and lactose concentrations during
      the middle of the trial. Outdoor ewes had lower SCC (P<0.003) and pH (P<0.001) in
      their milk than indoor ewes, whereas renneting parameters were not different
      across treatments. Results suggest that ewe welfare and productivity were not
      substantially affected by the housing system. The provision of feeding rations
      that meet the greater energy demand for maintenance is required to sustain
      productivity in outdoor reared sheep.

PMID- 11445424
TI  - Polymorphisms at the five exons of the growth hormone gene in the algarvia goat:
      possible association with milk traits.
AB  - The present preliminary study attempts to establish associations between milk
      production traits and genetic polymorphisms at the GH gene in the Algarvia goat.
      The DNA of 108 goats of the indigenous Portuguese Algarvia breed was evaluated.
      Single-strand conformation polymorphisms (SSCP) were identified at the five exons
      of the goat growth hormone (gGH) gene. Two conformational patterns were found in
      each of exons 1 and 2, four in exon 3, six in exon 4 and five in exon 5. An
      association between these SSCP patterns with milk, fat and protein production,
      and fat and protein content was examined. Patterns F/F of exon 4 and A/A of exon
      5 were positively associated with milk production (P<0.05). The results
      demonstrated that the gGH gene could be exploited as a candidate gene for marker
      assisted selection in goat breeds.

PMID- 11445425
TI  - Production performance of Barbados blackbelly sheep in Tobago, West Indies.
AB  - Data on 298 lambs from 161 ewes of the Barbados Blackbelly breed from 1982 to
      1985 at the Blenheim Sheep Station in Tobago were studied to determine the
      influence of lambing season-year, sex and type of birth on body weights of lambs
      at birth, at 56 days (weaning) and 6 months of age, preweaning daily gain and
      mortality. The effect of the lambing season-year on litter size (total number of
      lambs born, born alive and weaned per ewe lambing) and total lamb weight at
      weaning were examined. The flock averages for body weights of lambs at birth, at
      56 days and 6 months of age, preweaning daily gain and mortality were 2.75, 10.8,
      19.2, 0.152kg, and 18.3%, respectively. Averages for total number of lambs born,
      born alive and weaned were 1.92, 1.88, 1.51, respectively, and total lamb weight
      at weaning was 16.7kg. The lambing season-year effect was apparent for all traits
      studied except for litter size and lamb mortality. Sex of lamb was not a
      significant source of variation. Type of birth had significant effect on lamb
      growth traits and total lamb weight at weaning. Single born lambs were heavier
      than those born as twins or more. Ewes with triplets or more weaned 21kg lamb
      weight compared to 18 and 12kg for twins and singles, respectively. Lamb
      mortality was 27.8% for those with below average birth weight and 8.8% for those
      with above average birth weight (P<0.05).

PMID- 11445426
TI  - Growth performance of purebred Awassi, Morkaraman and Tushin lambs and their
      crosses under semi-intensive management in Turkey.
AB  - Growth performance of 168 Awassi (A), Morkaraman (M), Tushin (T) purebred lambs
      and their crosses AxM, MxT, AxM and TxM reared under semi-intensive management in
      Turkey were evaluated. The lambs grazed on pasture for 84 days and were provided
      with a concentrate diet (1.5-2.0% of their live weight). Birth weight and average
      daily weight gain during the pre-grazing period for M, A, T, MxT, AxM and TxM
      crossbred lambs were 2.91, 3.61, 3.70, 4.30, 2.63, and 3.79kg and 186, 129, 160,
      160, 163, and 168g, respectively. Corresponding estimates were 20, 15, 15, 17, 20
      and 19kg for initial fattening weight; 168, 169, 160, 176, 174 and 184g for
      average daily weight gain on fattening, and 34, 30, 28, 32, 35, and 34kg for
      final fattening weight, respectively. The amounts of concentrate consumed per kg
      weight gain in addition to grazing on pasture for purebred and crossbred lambs
      were 1.89, 1.86, and 1.97 and, 1.78, 1.82, and 1.71kg, respectively. The genotype
      of lamb and type of birth significantly affected the birth weight. Besides the
      genotype and the type of birth, age of dam and sex had a significant influence on
      the average daily weight gain during the pre-grazing period. Average daily weight
      gain during the fattening period was significantly affected by sex.

PMID- 11445427
TI  - General anti-microbial properties of the integument in fleece producing sheep and
      goats.
AB  - Based on lectin histochemical methods, this study describes the production and
      distribution of various terminal sugars in the integument of Merino sheep and
      Angora goats. Additionally, pH measurements were performed for information about
      environmental conditions of microbes on the skin surface and in the fleece. The
      results demonstrated strongly positive reactions for alpha-L-fucose in the
      stratum corneum of Merino sheep, and in the secretions of the skin glands of
      Angora goats. Moreover, alpha-D-mannose, beta-D-N-acetylglucosamine, alpha-D-N
      acetylgalactosamine, alpha-D-galactose and beta-D-galactose were very distinct in
      the secretions of the skin glands of both species. The skin products containing
      saccharide residues are deposited on the skin surface and in the fleece as part
      of wool grease, and the terminal sugars may be liberated by bacterial and fungal
      activities. All of these sugars are of specific interest because of their ability
      of inhibiting the adherence of different bacteria and fungi to the epidermal
      cells. Thus, free sugars impede attacks of skin micro-inhabitants against the
      integrity of the epidermal barrier. In contrast to these results, the skin pH
      conditions were strongly alkaline, particularly in the fleece of Merino sheep (pH
      6-9), so that proliferation of microbes may be promoted. This negative influence
      can only be countered by high production rates of sugar-containing skin products,
      which is normally the case based on long and intense activity of hair follicles
      in fine-wool producing sheep and goats.In conclusion, this study demonstrates
      that a basic anti-microbial biological system exists on the skin surface and
      within the hair coat, that operates with free sugars before the immune system is
      activated.

PMID- 11445428
TI  - Weaning and the ram-effect on fertility, serum luteinizing hormone and prolactin
      levels in spring rebreeding of postpartum Awassi ewes.
AB  - Spring rebreeding activity was investigated in 44 multiparous Awassi ewes
      allocated to one of three treatments. The first treatment entailed ewes suckling
      lambs for 45 days and then continuously exposed to fertile rams (Group 1); ewes
      of the second group were weaned at 14 days of age and then were either exposed
      continuously (Group 2) or intermittently (Group 3) to rams. Time of weaning and
      type of exposure to the ram did not influence the reproductive performance in
      terms of fertility and prolificacy in postpartum Awassi ewes. Time of weaning did
      not influence serum LH concentrations monitored at 3h intervals in Groups 1 and
      2. However, serum prolactin (PRL) concentrations were significantly higher in
      Group 1, compared to Group 2 of ewes. Serum LH levels at weaning were
      significantly higher in ewes that conceived and lambed, compared to ewes that did
      not. It was concluded that spring rebreeding of postpartum Awassi ewes did not
      respond to ram presence and/or early weaning in terms of improved reproductive
      performance. The lack of reproductive response was further reflected in LH and
      PRL profiles.

PMID- 11445429
TI  - Mutations prolong life in flies; implications for aging in mammals.

PMID- 11445430
TI  - Targeted disruption of C-type natriuretic peptide: a focused assault on
      cartilaginous bone.

PMID- 11445440
TI  - The isoprostanes in biology and medicine.
AB  - Isoprostanes are a new class of lipids, isomers of the conventional enzymatically
      derived prostaglandins, which are produced in vivo primarily by a free radical
      catalyzed peroxidation of polyunsaturated fatty acids. F2-isoprostanes, isomers
      of the enzyme-derived prostaglandin F2alpha, are the most studied species, but
      analogous isomers of other prostaglandins and leukotrienes have been described.
      Because of their mechanism of formation, specific structural features that
      distinguish them from other free radical-generated products and chemical
      stability, they can provide a reliable index for the oxidant component of several
      diseases in vivo. Consistent data suggest that formation of F2-isoprostanes is
      altered in a variety of clinical settings putatively associated with oxidant
      stress. Moreover, measurement of F2-isoprostanes might provide a sensitive
      biochemical basis for dose-selection in studies of natural and synthetic
      antioxidants. Finally, some F2-isoprostanes possess potent biological activities
      in vitro and in vivo, suggesting that they may also act as mediators of the
      cellular effects of oxidative stress.

PMID- 11445441
TI  - Physiological function of the orphans GCNF and COUP-TF.
AB  - Orphan nuclear receptors are members of the nuclear receptor superfamily of
      ligand-activated transcription factors for which ligands and functions have not
      been identified. Since the cloning of the original orphans, ligands have been
      identified for several orphan receptors that heterodimerize with the retinoid X
      receptor and are no longer classified as orphan receptors. Considering the
      central role that nuclear receptors play in differentiation, development,
      metabolic regulation, homeostasis and disease, it is crucial that we understand
      the roles of the remaining orphans. However, the identification of ligands for
      those orphans that form homodimers has proven more difficult. Thus, to gain
      greater insight into the functions of orphan receptors, gene targeting has been
      used to knock out these factors and study mouse development in their absence.
      Here we will review the progress made in understanding the roles of the orphans
      GCNF and the COUP-TFs with the use of gene knockouts.

PMID- 11445442
TI  - Signaling pathways activated by the growth hormone receptor.
AB  - In recent years, significant progress has been made in elucidating the signaling
      pathways activated by the growth hormone (GH) receptor. An initiating event is
      probably the activation of JAK2 (Janus kinase 2), a GH receptor-associated
      tyrosine kinase. Identification of the proteins recruited to the GH receptor-JAK2
      complex and dissection of the signaling pathways that are subsequently activated
      will ultimately provide a basis for understanding GH action at the molecular
      level.

PMID- 11445443
TI  - Endothelial dysfunction in endocrine disease.
AB  - In addition to diabetes mellitus and obesity, acromegaly, Cushing's syndrome,
      hypopituitarism, hypo- and hyperthyroidism, hyperparathyroidism and polycystic
      ovary syndrome are associated with either increased mortality from, or increased
      prevalence of, cardiovascular disease (CVD). Recently, endothelial dysfunction
      has been identified as an early marker of CVD and has been shown to predict
      future coronary artery disease, before atherosclerotic changes appear in
      arteries. Thus, measurement of endothelial function might identify at-risk
      individuals early and be a useful means of assessing response to treatment aimed
      at reducing long-term morbidity and/or mortality from CVD. Such studies are being
      undertaken in hypopituitarism and other endocrinopathies, and are reviewed
      herein. Endothelial function in large vessels can be measured noninvasively by
      ultrasound measurement of flow-mediated endothelium-dependent dilation (FMD).
      Serum markers of endothelial function, such as von Willebrand's factor,
      thrombomodulin, E-selectin and intercellular adhesion molecule 1, could be
      increased and be useful for evaluation of treatment, because they correlate
      inversely with FMD.

PMID- 11445444
TI  - Fatty acid transport proteins: a current view of a growing family.
AB  - Long-chain fatty acids (LCFAs) are a major caloric component of our diet and are
      key metabolites for energy generation and storage. Physiological uptake of LCFAs
      across cell membranes is a saturable and competable process occurring at low
      concentrations, indicative of protein-mediated transport. Fatty acid transport
      proteins are a family of transmembrane proteins that enhance LCFA uptake and are
      produced in all fatty acid-utilizing tissues. Here, we review our current
      understanding of the function, expression patterns and regulation and subcellular
      localization of this interesting family of proteins.

PMID- 11445445
TI  - In vivo assessment of the effects of estrogen on human brain.
AB  - There is increasing evidence from animal and in vitro studies to suggest that
      estrogen might have neuroprotective effects, and several plausible physiological
      mechanisms have been proposed. However, it is not yet fully understood how
      estrogen affects the human brain. There are several techniques that are currently
      employed for in vivo assessment of brain structure and function in humans,
      including neuropsychological and neuroendocrine testing, computerized tomography,
      structural and functional magnetic resonance imaging, magnetic resonance
      spectroscopy, single photon emission spectroscopy and positron emission
      tomography. Results from studies investigating the effects of estrogen on the
      female brain using the above techniques are reviewed here. The current data from
      humans suggest that the use of estrogen hormone-replacement therapy (HRT) in
      healthy, postmenopausal women might reduce the risk of developing Alzheimer's
      disease (AD) and preserve certain aspects of cognitive function. The use of HRT
      in postmenopausal women might also modulate neurotransmitter function and can
      increase cerebral blood flow in a regionally specific and task-dependent manner.
      In addition, the neuroprotective effects of HRT might depend on the length of its
      use. However, there is very little evidence at present that HRT is an effective
      treatment for established AD.

PMID- 11445446
TI  - Simian immunodeficiency virus from mandrill (Mandrillus sphinx) SIVmnd
      experimentally infects human and nonhuman primate cells.
AB  - This study set out to characterize the features of experimental infection by
      simian immunodeficiency virus in mandrill (SIVmnd) (Mandrillus sphinx),
      cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta),
      chimpanzee (Pan troglodytes), African green monkey (Cercopithecus pygerythrus),
      baboon (Papio cynocephalus) and human cells. Purified cells were exposed to a
      primary isolate of SIVmnd grown in the infected mandrill peripheral blood
      mononuclear cells, and viral p27 gag antigen was quantitated by antigen capture
      ELISA. Human cells have been found to be infected by SIVmnd. SIVmnd infection in
      cynomolgus macaque, rhesus macaque, baboon, mandrill and human cells were more
      effective than in vervet and chimpanzee cells. In addition, the lymphocytic cell
      lines SupT1, CEMx174 and Molt4 clone 8 were consistently infected by SIVmnd,
      whereas U937, a monocytic cell line, was not.

PMID- 11445447
TI  - Mycobacterial cord factor, but not sulfolipid, causes depletion of NKT cells and
      upregulation of CD1d1 on murine macrophages.
AB  - Trehalose 6,6'-dimycolate (TDM, cord factor) has frequently been used as an
      adjuvant to stimulate antibody production. Although it also induces cellular
      immunity, detailed studies about the underlying events do not exist. To determine
      the kinetics of TDM-specific changes promoting a T helper 1 (Th1) response, we
      injected mice with TDM or 2,3,6,6'-tetraacyl trehalose 2'-sulfate (SL,
      sulfolipid), another mycobacterial trehalose-containing glycolipid without
      mycolic acid. TDM, but not SL, caused a strong increase in serum interferon-gamma
      (IFN-gamma) levels 2 days later, accompanied by expansion of natural killer (NK)
      cells. Subsequent TDM effects included depletion of normal-density CD4(+)
      NK1.1(+) TCRalpha/beta(intermediate) cells from day 7 on, upregulation of MHC
      class II and CD1d1 on macrophages (peaking on day 21), and an increased
      proportion of Th1 cells evident after 3 weeks. TDM, but not a similar glycolipid
      without mycolic acid, can therefore initiate a cascade of events starting with
      strong release of IFN-gamma and NK cell expansion, resulting in the appearance of
      macrophages activated for antigen presentation. Our data therefore provide the
      basis for optimized immunization schedules with TDM as the adjuvant component of
      a Th1 vaccine.

PMID- 11445448
TI  - Burkholderia pseudomallei virulence: definition, stability and association with
      clonality.
AB  - Clinical presentations of melioidosis, caused by Burkholderia pseudomallei are
      protean, but the mechanisms underlying development of the different forms of
      disease remain poorly understood. In murine melioidosis, the level of virulence
      of B. pseudomallei is important in disease pathogenesis and progression. In this
      study, we used B. pseudomallei-susceptible BALB/c mice to determine the virulence
      of a library of clinical and environmental B. pseudomallei isolates from
      Australia and Papua New Guinea. Among 42 non-arabinose-assimilating (ara(-))
      isolates, LD(50) ranged from 10 to > 10(6) CFU. There were numerous correlations
      between virulence and disease presentation in patients; however, this was not a
      consistent observation. Virulence did not correlate with isolate origin (i.e.
      clinical vs environmental), since numerous ara(-) environmental isolates were
      highly virulent. The least virulent isolate was a soil isolate from Papua New
      Guinea, which was arabinose assimilating (ara(+)). Stability of B. pseudomallei
      virulence was investigated by in vivo passage of isolates through mice and
      repetitive in vitro subculture. Virulence increased following in vivo exposure in
      only one of eight isolates tested. In vitro subculture on ferric citrate
      containing medium caused attenuation of virulence, and this correlated with
      changes in colony morphology. Pulsed-field gel electrophoresis and randomly
      amplified polymorphic DNA typing demonstrated that selected epidemiologically
      related isolates that had variable clinical outcomes and different in vivo
      virulence were clonal strains. No molecular changes were observed in isolates
      after in vivo or in vitro exposure despite changes in virulence. These results
      indicate that virulence of selected B. pseudomallei isolates is variable, being
      dependent on factors such as iron bioavailability. They also support the
      importance of other variables such as inoculum size and host risk factors in
      determining the clinical severity of melioidosis.

PMID- 11445449
TI  - Staphylococcus aureus accessory regulators: expression within biofilms and effect
      on adhesion.
AB  - Many of the genes encoding the virulence factors for Staphylococcus aureus are
      controlled by the accessory gene regulator (agr) and staphylococcal accessory
      regulator (sar). This regulation may be affected by the environment in which the
      organisms are grown. In the majority of ecosystems, bacteria grow attached to
      surfaces and form biofilms. We used S. aureus strains containing mutations
      inactivating agr and sar to determine whether the presence of these genes
      influences the attachment of the bacterium to a surface. We also used strains
      harbouring reporter constructs of the agr and sar operons to determine their
      expression in biofilms. The attachment study results showed that the sarA mutant
      strain adhered better to glass than did the agrA mutant or the wild type. There
      was an increased adherence to fibronectin-coated glass for all three strains
      compared to glass. Thus, these adhesion studies demonstrate that agr and sar have
      pleiotrophic effects on the surface expression of molecules responsible for
      binding to different substrata. In the biofilms higher numbers of bacteria and
      the greatest expression were observed at the base, but there were no observable
      differences between the reporter constructs. Expression of the agr and sar
      reporter fusions was significantly higher in the deepest layers of the biofilms
      where the greatest numbers of bacteria were also observed, perhaps as one might
      expect for genes that are regulated in a cell density dependent fashion.

PMID- 11445450
TI  - Effect of the mouse Nramp1 genotype on the expression of IFN-gamma gene in early
      response to Salmonella infection.
AB  - The early interferon-gamma (IFN-gamma) response after Salmonella infection was
      compared in resistant and susceptible congenic mice strains differing by the
      allele of Nramp1. IFN-gamma gene expression in vivo was studied by quantitative
      reverse transcription-PCR performed from the spleen of mice challenged by
      Salmonella either in multiplication or in resting phase. The spleen colonisation
      by Salmonella in vivo was investigated and was shown to be identical in a
      genetically defined host, whatever the initial phase of the bacteria. However,
      the bacterial load of the spleen was significantly reduced in Nramp1(r)
      (resistant) mice compared to Nramp1(s) (susceptible) mice. The background level
      of IFN-gamma mRNA was higher in the spleen of resistant mice than in the
      susceptible mice, before infection. Interestingly, the early upregulation of IFN
      gamma gene transcription, which was observed after infection with Salmonella, was
      reproducibly delayed in susceptible mice compared to resistant mice. Finally, the
      kinetics of the host IFN-gamma response seems to be Nramp1 dependent. Resistant
      mice present the advantage of being more prompt to express this anti-infectious
      cytokine gene than susceptible mice in response to Salmonella infection.

PMID- 11445451
TI  - Y2K+1 state-of-the-art on non-peptide phosphoantigens, a novel category of
      immunostimulatory molecules.
AB  - Some human T cells are activated in vivo and in vitro by small non-peptide
      antigens, so-called phosphoantigens. Since their discovery in 1994, several
      reports have continuously documented novel members of this category of
      immunostimulatory molecules. This article reviews the current knowledge on their
      biochemical properties.

PMID- 11445453
TI  - Could anti-inflammatory medicines treat viral eye diseases?

PMID- 11445452
TI  - Immunity to Bordetella pertussis.
AB  - Bordetella pertussis exploits extracellular and intracellular niches in the
      respiratory tract and a variety of immune evasion strategies to prolong its
      survival in the host. This article reviews evidence of complementary roles for
      cellular and humoral immunity in protection. It discusses the effector mechanisms
      of bacterial elimination, the strategies employed by the bacteria to subvert
      protective immune responses and the immunological basis for systemic and
      neurological responses to infection and vaccination.

PMID- 11445454
TI  - The rise and fall of Viagra.

PMID- 11445458
TI  - Science with a smile - the limerick.

PMID- 11445455
TI  - Algal compound could reverse multidrug resistance in cancer.

PMID- 11445460
TI  - Bacterial fatty-acid biosynthesis: an antibacterial drug target waiting to be
      exploited.

PMID- 11445459
TI  - Antibiotic resistance: can we beat the bugs?
AB  - The Discussion Forum provides a medium for airing your views on any issues
      related to the pharmaceutical industry and obtaining feedback and discussion on
      these views from others in the field. You can discuss issues that get you hot
      under the collar, practical problems at the bench, recently published literature,
      or just something bizarre or humorous that you wish to share. Publication of
      letters in this section is subject to editorial discretion and company
      promotional letters will be rejected immediately. Furthermore, the views provided
      are those of the authors and are not intended to represent the views of the
      companies they work for. Moreover, these views do not reflect those of Elsevier,
      Drug Discovery Today or its editorial team. Please submit all letters to Rebecca
      Lawrence, News & Features Editor, Drug Discovery Today, e-mail:
      Rebecca.Lawrence@drugdiscoverytoday.com

PMID- 11445461
TI  - Drug discoverers - you need us - Reply.

PMID- 11445462
TI  - Efficacy of the anti-angiogenic approach to solid tumors.

PMID- 11445463
TI  - Phage display for target-based antibacterial drug discovery.
AB  - Increasing bacterial drug resistance and hard-to-eradicate opportunistic
      infections have created a need for new antibiotics. Sequencing of microbial
      genomes has yielded many new potential targets for antibacterial drug discovery.
      However, little is known about the biochemical activities of many of these
      targets, making it difficult to develop HTS assays for them. Peptides isolated by
      phage display can be used as 'surrogate ligands' in competition assays for
      screening of targets of unknown function with small-molecule libraries. These
      screening assays can be adapted into a variety of high-throughput formats,
      including those based on radioactive, luminescence or fluorescence detection.

PMID- 11445464
TI  - Muscle-based gene therapy and tissue engineering for the musculoskeletal system.
AB  - The recent expansion of molecular biology techniques has opened the gates for a
      rapid advancement in our knowledge of disease mechanisms. These techniques, in
      addition to advances in cell biology and polymer chemistry, are resulting in
      novel approaches to treating musculoskeletal disorders. Surgeons, who have
      traditionally used the tools of excision and reconstruction to treat patients,
      might now serve as surgical 'gardeners', who create microenvironments that are
      conducive for tissue regeneration. This review will update readers on the
      principles and current advances in muscle-based gene therapy and tissue
      engineering for the musculoskeletal system.

PMID- 11445465
TI  - Protein crystallization - is it rocket science?
AB  - Fueled by initial space shuttle results, the National Aeronautics and Space
      Administration (NASA) has been supporting fundamental studies of macromolecular
      crystal growth since 1985. The majority of this research is directed at
      understanding the relationship between experimental variables and important
      crystal characteristics. The program has resulted in new methods and technology
      that will benefit the crystallography community's effort to meet the ever
      increasing demand for protein structural information. Microgravity
      crystallization results indicate a potential impact on structural biology's more
      challenging problems, as soon as long-duration experiments can be performed on
      the International Space Station.

PMID- 11445466
TI  - Monitor: molecules and profiles.
AB  - Monitor provides an insight into the latest developments in drug discovery
      through brief synopses of recent presentations and publications together with
      expert commentaries on the latest technologies. There are two sections: Molecules
      summarizes the chemistry and the pharmacological significance and biological
      relevance of new molecules reported in the literature and on the conference
      scene; Profiles offers commentary on promising lines of research, emerging
      molecular targets, novel technology, advances in synthetic and separation
      techniques and legislative issues.

PMID- 11445467
TI  - Novel antiviral molecules.

PMID- 11445468
TI  - DNA dumbbells: decoys for gene-regulatory proteins.

PMID- 11445469
TI  - Insulin-like growth factor I and prostate cancer.

PMID- 11445470
TI  - Hemostatic laparoscopic partial nephrectomy: initial experience with the
      radiofrequency coagulation-assisted technique.
AB  - OBJECTIVES: The techniques for hemostasis after renal tumor excision have limited
      the widespread application of laparoscopic partial nephrectomy (LPN). To improve
      hemostasis and aid visualization, we report our experience with a novel
      radiofrequency coagulation (RFC) technique for LPN. METHODS: Ten patients
      underwent RFC-assisted LPN. The demographic and perioperative data were
      tabulated. Patients were positioned as for laparoscopic nephrectomy, and
      laparoscopic ports were placed. The kidney within Gerota's fascia was mobilized,
      and the fat overlying the tumor was carefully removed for pathologic evaluation.
      Under laparoscopic guidance, a radiofrequency probe was percutaneously inserted
      into the lesion and deployed to coagulate the lesion and a margin of normal
      parenchyma. Laparoscopic scissors were used to excise the lesion; additional
      hemostatic maneuvers were used selectively. RESULTS: The mean renal tumor size
      was 2.1 cm (range 1.0 to 3.2). The median operative time was 170 minutes and the
      median blood loss was 125 mL. The RFC technique resulted in complete tissue
      coagulation within the treated volume, thereby facilitating intraoperative
      visualization, minimizing blood loss, and permitting rapid and controlled tumor
      resection. The renal architecture was preserved, allowing accurate diagnosis of
      renal cell carcinoma and angiomyolipoma in 9 and 1 cases, respectively. No
      perioperative complications occurred. CONCLUSIONS: The use of RFC is an effective
      method to facilitate LPN of both exophytic and endophytic masses. By coagulating
      a margin of normal parenchyma, the technique minimizes blood loss and improves
      visualization during LPN. We anticipate this technique will broaden the clinical
      application for LPN.

PMID- 11445471
TI  - A new injectable bulking agent for treatment of stress urinary incontinence:
      results of a multicenter, randomized, controlled, double-blind study of
      Durasphere.
AB  - OBJECTIVES: To assess the safety and effectiveness of Durasphere compared with
      bovine collagen in the treatment of stress urinary incontinence (SUI) due to
      intrinsic sphincter deficiency (ISD). METHODS: This multicenter, randomized,
      controlled, double-blind trial was composed of 355 women diagnosed with SUI due
      to ISD and used a standardized pad test and the Stamey continence grade as the
      primary endpoints. The participants' ages ranged from 26 to 84 years. All
      patients had an abdominal leak point pressure of less than 90 cm H(2)O (average
      51). RESULTS: At 12 months after the first injection, the two materials were
      equivalent with respect to the improvement in continence grade and pad weight
      testing. Less Durasphere was injected to obtain comparable clinical results
      (Durasphere 4.83 mL versus bovine collagen 6.23 mL, P <0.001). When examined 1
      year after the date of the last treatment, 49 (80.3%) of the 61 women treated
      with Durasphere showed improvement of 1 continence grade or more compared with 47
      (69.1%) of 68 women treated with bovine collagen (P value for difference =
      0.162). Although the adverse events reported for both groups were similar, the
      Durasphere group had an increased short-term risk of urgency and urinary
      retention. CONCLUSIONS: The use of Durasphere for the treatment of SUI due to ISD
      was equally effective as bovine collagen and used less material. The U.S. Food
      and Drug Administration granted market approval for Durasphere on September 13,
      1999. The product design and initial clinical data suggest the potential for
      greater durability of the clinical benefit, with the possibility of a permanent
      solution for SUI due to ISD in some patients.

PMID- 11445472
TI  - Impact of power index, hydroureteronephrosis, stone size, and composition on the
      efficacy of in situ boosted ESWL for primary proximal ureteral calculi.
AB  - OBJECTIVES: The efficacy, safety, feasibility, and outcome of in situ treatment
      applied to select proximal ureteral calculi was assessed and analyzed with a view
      to avoiding auxiliary interventions and providing high clearance rates in the
      shortest possible time. We studied the impact of several clinically important
      variables, including power index, degree of hydroureteronephrosis (HDUN), stone
      size, and composition on the efficacy of sequential in situ boosted
      extracorporeal shock wave lithotripsy (ESWL) in a select group. The power index
      requirement for the in situ boosted protocol and the impact of the stone
      size/composition, degree of HDUN, and clearance rates were also analyzed.
      METHODS: An in situ (no instrumentation) boosted protocol was applied to 130
      primary unimpacted proximal ureteral calculi with no prior intervention. A
      typical session with the Siemens Lithostar Plus comprised 3000 shock waves, in
      installments of 500, deployed at a power setting of 1 to 4 kV with a gradual
      stepwise escalation. Sequential boosted additional sessions of ESWL were
      administered on days 2, 7, and 14, tailored to the degree of fragmentation,
      clearance status, and amount of residual stone bulk. Several parameters (shock
      waves, kilovolts used, fluoroscopy time, number of sessions, stone size,
      composition, fragmentation, clearance, and HDUN) were recorded and the results
      analyzed statistically. RESULTS: The results were excellent in 83.8%, with a mean
      duration to complete clearance of 11.3 days. In situ ESWL failed in 7.69%, and
      the auxiliary intervention rate was 10.7%. Pre-ESWL HDUN was present in 78.3%,
      the mean power index was 184.6/session/case, and the average stone burden was 8.9
      mm(2). Calcium oxalate monohydrate was the most common stone (56%). Renal colic
      was the most common side effect observed. The power index, fragmentation at the
      first session, and stone size were found to be the most favorable significant
      variables affecting stone clearance. The degree of HDUN, number of sessions, and
      stone composition did not significantly impact the clearance rates. CONCLUSIONS:
      In situ boosted ESWL should be the first-line therapeutic modality in select
      unimpacted primary proximal ureteral stones.

PMID- 11445473
TI  - Transperitoneal laparoscopic nephrectomy for giant polycystic kidneys: a case
      control study.
AB  - OBJECTIVES: To describe the technique and compare the surgical outcomes of
      patients with autosomal dominant polycystic kidney disease (ADPKD) undergoing
      laparoscopic or open nephrectomy for giant kidneys. METHODS: The surgical outcome
      of our first 10 consecutive patients with ADPKD who underwent laparoscopic
      nephrectomy was analyzed from a large prospective computer database. The results
      were compared with the 10 most recent open nephrectomy procedures performed for
      ADPKD at the same institution. To facilitate safe laparoscopic hilar dissection,
      the kidneys were made manageable by volume reduction, accomplished through
      diligent cyst puncture and aspiration using a novel prototype suction device with
      a beveled tip. RESULTS: No statistically significant differences were found
      between the laparoscopic and open surgical groups relative to patient sex, age,
      or median preoperative kidney size (24.0 versus 21.5 cm, respectively). The
      laparoscopic patients were significantly heavier than their open counterparts (94
      versus 78 kg, P = 0.0095) and had a longer operative time (247 versus 205
      minutes, P = 0.04). One conversion to open surgery occurred in the laparoscopic
      group because cysts were adherent to the spleen and colonic mesentery. No
      intraoperative complications or deaths occurred in either group and the
      postoperative complications were similar. The mean length of the postoperative
      hospitalization was markedly reduced with the laparoscopic compared with the open
      approach (2.6 versus 6.6 days, P = 0.00002). At a median of 12 months after
      surgery, none of the laparoscopic patients had recurrent pain, bleeding, or
      infection. CONCLUSIONS: Laparoscopic nephrectomy is technically safe and feasible
      in patients with ADPKD. Progressive cyst aspiration is a critical step,
      facilitating the identification of vital structures and the creation of enough
      abdominal cavity space to operate. The advantages of this minimally invasive
      technique include a short hospital stay, minimal pain, low morbidity, and
      superior cosmesis.

PMID- 11445474
TI  - Sacral bladder denervation for treatment of detrusor hyperreflexia and autonomic
      dysreflexia.
AB  - OBJECTIVES: Detrusor hyperreflexia after spinal cord injury may cause urinary
      incontinence and chronic renal failure. In patients refractory to conservative
      treatment and not eligible for ventral sacral root stimulation for electrically
      induced micturition, we investigated the therapeutic value of sacral bladder
      denervation as a stand-alone procedure. METHODS: Nine patients (8 men and 1
      woman) between 21 and 58 years old (mean 30.2) with traumatic suprasacral spinal
      cord lesions underwent sacral bladder denervation for treatment of detrusor
      hyperreflexia and/or autonomic dysreflexia. RESULTS: Detrusor hyperreflexia and
      autonomic dysreflexia were eliminated in all cases. Bladder capacity increased
      from 177.8 +/- 39.6 to 668.9 +/- 64.3 mL; intravesical pressure decreased from
      89.3 +/- 19.1 to 20.2 +/- 2.7 cm H(2)O. For facilitating clean intermittent
      catheterization (CIC), 4 patients received a continent vesicostomy in a second
      stage procedure; one of them in combination with bladder augmentation. Four
      patients empty their bladder by way of urethral CIC. One completely tetraplegic
      patient has an indwelling urethral catheter. In the 5 patients with autonomic
      dysreflexia, the systolic blood pressure was lowered from 196 +/- 16.9 to 124 +/-
      9.3 mm Hg and the diastolic blood pressure from 114 +/- 5.1 to 76 +/- 5.1. The
      annual frequency of urinary tract infections decreased from 9 +/- 1.2 to 1.8 +/-
      0.7. In all patients, renal function remained stable. CONCLUSIONS: In selected
      patients with detrusor hyperreflexia and/or autonomic dysreflexia, sacral bladder
      denervation is a valuable treatment option. It is only moderately invasive in
      nature, requires neither sophisticated nor expensive medical equipment, and is an
      attractive alternative to urinary diversion using intestinal segments.

PMID- 11445475
TI  - Standing cystourethrogram: an outcome measure after anti-incontinence procedures
      and cystocele repair in women.
AB  - OBJECTIVES: To evaluate the standing voiding cystourethrogram (VCUG) with lateral
      views as an outcome measure to objectively document the correction of the
      urethral angle and cystocele in women who underwent various types of pelvic
      surgery. METHODS: A control group of 76 continent patients was selected who had
      VCUGs performed for indications other than incontinence. Patients with
      preoperative and postoperative VCUGs after anterior vaginal wall suspension for
      urethral hypermobility and grade 1 or 2 cystocele (UH group) or repair of grade 3
      cystocele (C group) were selected and compared with age-matched controls from the
      control group. RESULTS: Among the control group, the mean +/- SD urethral angle
      at rest was 12.5 degrees +/- 13.1 degrees and the urethral angle at straining was
      24.7 degrees +/- 15.6 degrees (P <0.001). The urethral angle at rest increased
      significantly from women in their 20s to their 80s. In the UH group (n = 52), the
      preoperative mean urethral angle at rest and at straining was 25.7 degrees +/-
      13.6 degrees and 42.6 degrees +/- 15.9 degrees, respectively, a difference of
      approximately 20 degrees. The postoperative urethral angles at rest and at
      straining did not statistically differ from those of the age-matched controls. In
      the C group (n = 36), the postoperative urethral angle at rest did not
      statistically differ from that of the age-matched controls. The lateral height of
      the cystocele demonstrated significant improvement in the UH and C groups.
      CONCLUSIONS: The standing VCUG is a reproducible outcome measure to
      preoperatively and postoperatively document the urethral angle. Using age-matched
      controls, a more objective definition of urethral hypermobility was obtained.
      Changes in cystocele height were observed postoperatively with a return to
      comparable age-matched control values.

PMID- 11445476
TI  - Application of the Mitrofanoff principle for intermittent self-catheterization in
      quadriplegic patients.
AB  - OBJECTIVES: Patients with cervical spinal cord lesions have impaired hand
      function, which often prohibits clean intermittent self-catheterization (CIC),
      especially in female patients. Enabling these patients to perform CIC gives them
      control of their bladder management and can improve their quality of life
      considerably. We have used an appendicovesicostomy to provide easy access for CIC
      in such patients. METHODS: Five patients (4 women, 1 man) with a mean age of 31
      years (range 20 to 52) and a mean duration of the cervical cord lesion of 22
      months (range 7 to 37) underwent appendicovesicostomy. Three patients were young
      victims of motor vehicle accidents, 1 patient had a progressive rheumatoid
      arthritic disorder, and 1 patient had a complex functional paraplegia syndrome
      and underwent bladder augmentation at the same time. RESULTS: The surgical
      procedure with the creation of a catheterizable stoma in the right lower
      abdominal quadrant was successful in all cases but was complicated by mechanical
      ileus in the patient with simultaneous bladder augmentation. All patients learned
      to perform independent CIC with continuing anticholinergic medication. Stomal
      stenosis did not occur in any of the 5 patients, and urinary tract infections
      occurred once in 2 patients and repeatedly in 1 patient. Three of 5 patients have
      been enabled by independent bladder management to achieve occupational
      rehabilitation. CONCLUSIONS: Appendicovesicostomy is a suitable procedure in
      patients with cervical spinal cord lesions who are otherwise unable to perform
      independent CIC. The creation of a catheterizable abdominal stoma enables these
      patients to gain independent control of their bladder management. However,
      caution in patient selection is advisable as probably the best results are
      achieved in highly motivated, younger patients with traumatic cervical cord
      lesions.

PMID- 11445477
TI  - Spontaneous late rupture of orthotopic detubularized ileal neobladders: report of
      five cases.
AB  - OBJECTIVES: To report five spontaneous ruptures in 4 patients. Spontaneous late
      rupture of orthotopic ileal bladder replacements is a rare complication of
      continent urinary diversion. METHODS: Four recurrence-free patients aged 36 to 68
      years experienced apparently spontaneous rupture of continent orthotopic ileal
      bladder replacement 3 months to 3 years after curative radical cystectomy and
      urinary diversion for invasive bladder cancer. Ileal bladder rupture occurred
      twice in 1 patient with an interval of 9 months. RESULTS: All 4 patients had had
      a good result from their diversion procedure and had reported complete day and
      nighttime continence before the spontaneous rupture. The spontaneous rupture was
      evidently caused by overdistension of the ileal neobladder in four of five
      instances. In addition to overdistension, a second factor such as minor blunt
      abdominal trauma or urethral occlusion was identifiable in two instances. The
      rupture occurred in the right upper corner of the ileal bladder in four of five
      instances and led to acute and severe abdominal pain. Cystography was done in
      three instances, but was diagnostic in only 2 cases. The histologic examination
      of the excised bladder wall margins revealed nonspecific inflammatory changes in
      3 cases. Open surgical drainage and repair was successfully undertaken in all
      cases. CONCLUSIONS: The circumstances of the cases described suggest that late
      spontaneous rupture of an orthotopic ileal bladder replacement is not related to
      the surgical technique but rather to factors of patient compliance and medical
      management.

PMID- 11445478
TI  - Pilot study of dietary fat restriction and flaxseed supplementation in men with
      prostate cancer before surgery: exploring the effects on hormonal levels,
      prostate-specific antigen, and histopathologic features.
AB  - OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer
      progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may
      thwart prostate cancer. The potential effects of flaxseed may be enhanced with
      concomitant fat restriction. We undertook a pilot study to explore whether a
      flaxseed-supplemented, fat-restricted diet could affect the biomarkers of
      prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were
      awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or
      less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels
      of prostate-specific antigen, testosterone, free androgen index, and total serum
      cholesterol were determined. The tumors of diet-treated patients were compared
      with those of historic cases (matched by age, race, prostate-specific antigen
      level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal
      deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling
      [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was
      34 days (range 21 to 77), during which time significant decreases were observed
      in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total
      testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index
      (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up
      levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL,
      respectively, for the entire sample (P = 0.58); however, among men with Gleason
      sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1
      ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic
      controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The
      distribution of the apoptotic indexes differed significantly (P = 0.01) between
      groups, with most historic controls exhibiting TUNEL categorical scores of 0;
      diet-treated patients largely exhibited scores of 1. Both the proliferation rate
      and apoptosis were significantly associated with the number of days on the diet
      (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest
      that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer
      biology and associated biomarkers. Further study is needed to determine the
      benefit of this dietary regimen as either a complementary or preventive therapy.

PMID- 11445479
TI  - Phase II trial of bicalutamide in patients with advanced prostate cancer in whom
      conventional hormonal therapy failed: a Southwest Oncology Group study (SWOG
      9235).
AB  - OBJECTIVES: To determine the efficacy and tolerability of bicalutamide in
      patients with advanced prostate cancer with progression after conventional
      hormonal therapy. METHODS: Fifty-two patients received bicalutamide, 150 mg once
      daily, as second-line therapy after progressing following treatment with
      orchiectomy or luteinizing hormone-releasing hormone analogue or
      diethylstilbestrol, alone or in combination. Patients had measurable (n = 8) or
      assessable (n = 44) disease, a Southwest Oncology Group performance status of 0
      to 2, and no prior antiandrogen therapy or chemotherapy. The objective response
      to treatment was assessed every 12 weeks; symptoms and pain were assessed monthly
      with questionnaires for 6 months. RESULTS: There was evidence of palliation with
      three measures of pain and, to a lesser extent, with a measure of overall symptom
      status after 3 months of taking bicalutamide. No complete or partial responses
      occurred. However, 9 (20%) of 44 subjects with adequate prostate-specific antigen
      data had a 50% or higher decrease in their prostate-specific antigen levels,
      which did not correlate with symptom improvement. The median survival time was 15
      months. The most common side effects were hot flashes (23%) and nausea (21%).
      CONCLUSIONS: These data suggest that bicalutamide decreases pain and improves
      symptom status in patients with prostate cancer in whom first-line hormonal
      therapy failed.

PMID- 11445480
TI  - Phase I trial of weekly paclitaxel plus oral estramustine phosphate in patients
      with hormone-refractory prostate cancer.
AB  - OBJECTIVES: To exploit the favorable dose intensity and safety profile of weekly
      paclitaxel, we conducted a Phase I trial of paclitaxel by 3-hour infusion in
      combination with estramustine phosphate (EM) in men with hormone-refractory
      prostate cancer (HRPC). The antimicrotubule drug combination of paclitaxel by 96
      hour infusion plus EM is active in HRPC. METHODS: Twenty-four patients with
      metastatic HRPC and progressive tumor after antiandrogen withdrawal were enrolled
      in this study. Oral EM was taken at a dose of 600 mg/m(2) daily for the initial
      21 patients and on a reduced schedule of 280 mg twice daily for the final 3
      patients. Paclitaxel was escalated from 60 to 118 mg/m(2). RESULTS: The major
      toxicities were gastrointestinal and thromboembolic complications related to
      daily oral dosing of EM. Of the first 21 patients, one third (n = 7) discontinued
      therapy within 4 weeks because of protracted nausea and/or thrombotic
      complications. Dose-limiting toxicities at 118 mg/m(2) paclitaxel were fatigue
      and hepatotoxicity. Of 13 patients with measurable soft-tissue lesions, 6 had
      objective partial regressions, and 9 (37.5%) of 24 patients (95% confidence
      interval 19.1% to 59.1%) with elevated prostate-specific antigen levels had a 50%
      or greater decline of at least 4 weeks' duration. CONCLUSIONS: Weekly paclitaxel
      at doses of 60 to 107 mg/m(2) were feasible in combination with oral EM, but
      daily oral EM produced unacceptable toxicity. On the basis of these results, a
      Phase II trial of weekly paclitaxel with the reduced dose and schedule of EM was
      initiated by the Eastern Cooperative Oncology Group to assess further the
      benefits and risks of this treatment in men with metastatic HRPC.

PMID- 11445481
TI  - Early experience in intermediate-risk penile cancer with sentinel node
      identification using the gamma probe.
AB  - OBJECTIVES: To report the initial experience with sentinel node identification
      using the gamma probe in patients with intermediate-risk penile cancer (T2NXM0,
      or T1 with intermediate or high-grade disease) and impalpable groin nodes.
      METHODS: Technetium-99m-labeled sulfur colloid was injected at the site of
      primary penile carcinoma 1 hour before surgery. The sentinel lymph nodes were
      located using the gamma probe and excised through a 3-cm inguinal incision. A
      full groin dissection was performed only in cases in which frozen section of the
      node demonstrated metastasis. RESULTS: Nine sentinel nodes were identified by the
      gamma probe and excised in 5 men. In 3 patients, the sentinel nodes were negative
      bilaterally. In 2 patients, the sentinel node, although grossly normal, showed a
      single focus of metastasis by frozen section analysis. In both of these patients,
      a full groin dissection was carried out and revealed no other nodal metastases.
      All 5 remained free of recurrence (median follow-up 18 months, range 16 to 23).
      CONCLUSIONS: In patients with microscopic involvement of a single lymph node only
      (confirmed by full groin dissection), gamma probe identification was 100%
      accurate. None of the patients with negative sentinel nodes had a recurrence.
      Biopsy of the sentinel nodes using the gamma probe can predict the presence or
      absence of inguinal node metastasis in patients with intermediate-risk penile
      cancer, sparing many patients the long-term morbidity of a full groin dissection.
      These initial results suggest further study is warranted.

PMID- 11445482
TI  - Outcome of intracytoplasmic sperm injection in azoospermic patients: stressing
      the liaison between the urologist and reproductive medicine specialist.
AB  - OBJECTIVES: To analyze the outcome of intracytoplasmic sperm injection (ICSI)
      cycles in infertile couples in whom the main diagnosis of infertility was
      azoospermia of obstructive and nonobstructive origin. METHODS: Eighty-three
      consecutive ICSI cycles were carried out with retrieved testicular or epididymal
      spermatozoa, 60 cycles in 32 patients with obstructive azoospermia and 23 cycles
      in 12 patients with nonobstructive azoospermia. Fifty-four testicular biopsies
      (testicular sperm extraction) and 18 epididymal aspirations (microepididymal
      sperm aspiration) were performed.Results. Motile spermatozoa were recovered in 65
      cycles (90.3%). In another 3 (4.2%), nonmotile spermatozoa were retrieved. In 4
      patients (5.5%), sperm could not be recovered. In 11 cycles, frozen sperm from a
      previous procedure were used. A significantly lower fertilization rate (64%
      versus 73%, P = 0.02), clinical pregnancy rate (13% versus 47%, P <0.001), and
      good embryo quality rates (35% versus 56%, P = 0.009) were observed in patients
      with nonobstructive azoospermia. In patients with obstructive azoospermia, no
      significant differences were observed when the outcome was analyzed on the basis
      of the sperm origin (ie, from testicular sperm extraction or microepididymal
      sperm aspiration). CONCLUSIONS: When combining testicular sperm extraction or
      microepididymal sperm aspiration with ICSI in patients with obstructive
      azoospermia, the results in terms of fertilization, implantation, and pregnancy
      rates were similar to those found in patients with nonazoospermic obstruction who
      underwent ICSI with ejaculated sperm. Patients with nonobstructive azoospermia
      had lower fertilization, embryo quality, and pregnancy rates than did those with
      obstructive azoospermia, probably because of severe defects in spermatogenesis,
      leading to poor gamete quality. The urologist and reproductive endocrinologist
      now have an excellent therapeutic option to offer men with previously intractable
      infertility.

PMID- 11445483
TI  - Pelvic venoablation with ethanol for the treatment of erectile dysfunction due to
      veno-occlusive dysfunction.
AB  - OBJECTIVES: To perform pelvic venoablation with ethanol injection into the deep
      dorsal vein for the treatment of 10 patients with venogenic erectile dysfunction.
      This procedure was easily performed without any selective embolization technique.
      The efficacy and safety of this technique are discussed. METHODS: A total of 10
      patients with veno-occlusive dysfunction, severe enough to make vaginal insertion
      impossible, underwent pelvic venoablation with ethanol. The mean patient age was
      67.1 years. Under spinal anesthesia, after the venous leaks were identified by
      cavernosography, a 20-gauge flexible needle was inserted into the deep dorsal
      vein. The pelvic venogram obtained with deep dorsal venography was included in
      what was revealed by the venogram obtained with cavernosography. A mixture of
      absolute ethanol and contrast medium (4:1) was used as a sclerosing agent. Under
      fluoroscopic control, the sclerosing agents were injected into the deep dorsal
      vein through a flexible needle. Success was defined as the ability to achieve
      vaginal insertion without the aid of any drugs, vasoactive injections, penile
      prosthesis, or vacuum device. RESULTS: The follow-up ranged from 25 to 37 months
      (mean 32.3). At the short-term follow-up visit (less than 6 months), 7 patients
      (70%) reported erections sufficient for vaginal insertion; at the long-term
      follow-up visit, 5 men (50%) reported sustained, sufficient potency and 5 (50%)
      reported persistent erectile dysfunction. No serious complications occurred.
      CONCLUSIONS: Our pelvic venoablation technique using ethanol was effective,
      minimally invasive, and cost-effective.

PMID- 11445484
TI  - Free thiols in human spermatozoa: correlation with sperm DNA integrity.
AB  - OBJECTIVES: To examine the levels of sperm protamine free sulfhydryl or thiol
      (SH) groups and DNA denaturation (DD) in semen from fertile and infertile
      men.Methods. Semen samples were obtained from consecutive nonazoospermic men
      presenting for infertility evaluation (n = 66) and fertile men presenting for
      vasectomy (n = 10). The standard semen parameters (sperm concentration, motility,
      and morphology), sperm DD, and SH content were monitored. Sperm DNA integrity was
      evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and
      expressed as the percentage of spermatozoa demonstrating denatured DNA. RESULTS:
      The mean (+/- SE) levels of sperm SH groups and the percentage of spermatozoa
      with DD were significantly higher in the infertile men than in the fertile men
      (SH groups 1083 +/- 97 and 570 +/- 101 nmol/10(6) spermatozoa, respectively; and
      DD 21% +/- 1.7% and 8.9% +/- 1.9%, respectively). The levels of sperm SH groups
      and DD correlated positively (r = 0.53). Also, the levels of sperm SH groups and
      DD correlated negatively with the standard semen parameters. CONCLUSIONS: Our
      data demonstrate that sperm SH content correlates positively with sperm DD and
      that significantly higher levels of sperm DD and SH content are found in
      infertile men than are found in fertile men. These data suggest that the enhanced
      susceptibility of sperm DNA to denaturation in infertile compared with fertile
      men may be associated with incomplete oxidation of the sperm SH groups.

PMID- 11445485
TI  - Nitric oxide synthase activity in human seminal plasma.
AB  - OBJECTIVES: To determine whether human seminal plasma possesses nitric oxide
      synthase (NOS) activity and whether, if present, this activity correlates with
      standard semen analysis parameters. Recent studies have demonstrated the presence
      of NOS in the epithelium of the male reproductive tract and have shown that
      nitric oxide can influence human sperm function in vitro. METHODS: Semen samples
      were collected from 30 men presenting for an infertility evaluation at our
      institution. After a standard semen analysis, the semen samples were centrifuged
      at 10,000g, and the seminal plasma was collected and stored at -20 degrees C for
      later evaluation of the arginine concentration and calcium-dependent and calcium
      independent NOS activity. NOS activity was measured by the conversion of [(3)H]L
      arginine to [(3)H]L-citrulline. RESULTS: NOS activity was detected in 28 of 30
      seminal plasma samples tested. The mean +/- SD calcium-dependent NOS activity was
      1.6 +/- 0.8 nmol/min/mL and the mean calcium-independent NOS activity was 1.0 +/-
      0.7 nmol/min/mL of the seminal plasma. The mean +/- SD arginine concentration in
      the seminal plasma was 7.0 +/- 1.9 mM. No significant correlations were found
      between the NOS activity in the seminal plasma and sperm concentration, sperm
      motility, or leukocyte concentration. The 2 men without detectable NOS activity
      in their semen had documented congenital bilateral absence of the vas deferens.
      CONCLUSIONS: The results of this study demonstrate the presence of NOS activity
      in human semen and support a role of nitric oxide in sperm function in vivo. Our
      results also suggest that the seminal vesicles may be an important source of NOS
      activity in semen.

PMID- 11445486
TI  - Testicular effect of mustard gas.
AB  - OBJECTIVES: To explain the testicular effect of mustard gas. METHODS: Eighty-one
      patients who had been exposed to sulfur mustard and had the presenting symptom of
      infertility underwent evaluation of their reproductive system. Three semen
      analyses, serum hormonal determinations (luteinizing hormone, follicle
      stimulating hormone, and testosterone), and genital examinations were completed
      for all patients, as were testicular biopsies in 24 patients. RESULTS:
      Azoospermia and severe oligospermia were diagnosed in 42.5% and 57.5% of
      patients, respectively. Hormone studies revealed an elevated plasma follicle
      stimulating hormone level and normal plasma luteinizing hormone and testosterone
      concentrations. Testicular biopsy showed selective atrophy of the germinal
      epithelium, intact Sertoli cells, and normal-appearing Leydig cells. CONCLUSIONS:
      Mustard gas can cause defective spermatogenesis years after exposure.

PMID- 11445487
TI  - Therapeutic effects of high-dose isoxsuprine in the management of mixed-type
      impotence.
AB  - OBJECTIVES: To determine the effectiveness and safety of high-dose isoxsuprine
      for the treatment of mixed-type erectile dysfunction. METHODS: Forty-four
      patients who had vasculogenic impotence diagnosed on the basis of their sexual
      history, physical examination, laboratory analysis, polysomnographic recording of
      nocturnal erections, and dynamic color Doppler sonography of the cavernosal
      arteries were entered into a randomized, double-blind, placebo-controlled,
      crossover comparison of a placebo with high-dose isoxsuprine hydrochloride (60
      mg/day orally). The treatment consisted of two 30-day courses. After a 14-day
      washout period, the patients who initially received the placebo for 30 days
      switched to isoxsuprine hydrochloride for 30 days and vice versa. Erectile
      function, ejaculation, interest in sex, and physical examination findings were
      investigated before treatment and at the end of each drug period. RESULTS: Thirty
      six patients (82%) completed the entire treatment schedule. Positive clinical
      results (complete and partial responses) were obtained in 6 men (16.6%) at the
      end of the isoxsuprine phase and in 7 men (19.4%) after the placebo period. The
      statistical analysis disclosed no significant difference when isoxsuprine was
      compared with placebo (P >0.05). Significant drug-related adverse effects
      occurred in the isoxsuprine group and treatment was discontinued in 2 patients.
      CONCLUSIONS: Isoxsuprine is no better than placebo as a first-line treatment for
      mixed-type erectile dysfunction.

PMID- 11445488
TI  - Management of prepubertal varicoceles-results of a questionnaire study among
      pediatric urologists and urologists with infertility training.
AB  - OBJECTIVES: Varicoceles are a common condition affecting male fertility seen by
      urologists. However, prepubertal varicoceles are much less common and their
      management is controversial. We designed a questionnaire to assess the practice
      patterns among urologists (pediatric urologists/urologists with infertility
      training) with regard to prepubertal varicocele management. METHODS: A 15-point
      questionnaire pertaining to management issues of prepubertal varicoceles was sent
      to 150 pediatric urologists and 150 urologists with infertility training. Two
      clinical scenarios referring to treatment algorithms of prepubertal varicoceles
      were included. RESULTS: Of the 300 questionnaires mailed, 174 urologists (58%)
      responded. Seventy-five of the respondents were urologists with an interest in
      infertility, and 99 were pediatric urologists. Of the 174 respondents, 86.2%
      treated prepubertal varicoceles and 13.8% referred patients to interventional
      radiologists for embolization. The ratio of varicocelectomy to expectant
      management was about equal between urologists with infertility training and
      pediatric urologists (46% versus 54%). A difference in testicular size was the
      most common indication for varicocelectomy (80.5%), followed by pain (51.1%) and
      potential fertility problems (24.7%). About one third of all urologists would
      perform varicocelectomy on patients of any age and seven (4%) would not operate
      before puberty. In 136 responses (78.2%), follow-up information was not
      available. Among the 35 respondents with follow-up information (21.8%), 21
      reported infertility occurring after varicocelectomy and 16 after expectant
      management. If varicocelectomy was performed, most urologists (47.2%) used
      magnification loupes, 29.3% used microscopes, and 29% used no magnification. The
      preferred approach was inguinal (Ivanissevich) in 35.6% followed by subinguinal
      in 30%; 21% performed retroperitoneal varicocelectomy (Palomo) and 9.8% used a
      laparoscopic approach. Of the 300 complications reported, postoperative
      hydroceles were the most common (40.4%), followed by recurrence (20.8%) and
      hematomas (17.4%). CONCLUSIONS: The management of prepubertal varicoceles is
      controversial among different urologic subspecialties (pediatric
      urology/infertility). Differences include indications, timing, and techniques
      used for varicocelectomy. Accurate follow-up information for children with
      prepubertal varicoceles is rare. A prospective randomized study comparing
      varicocelectomy versus expectant management of prepubertal varicoceles is needed
      to assess the outcomes and define uniform treatment criteria.

PMID- 11445489
TI  - Unusual presentation of xanthogranulomatous pyelonephritis.

PMID- 11445490
TI  - Paraneoplastic limbic encephalitis, a complication of the testicular cancer.
AB  - We report a case of paraneoplastic limbic encephalitis related to a testicular
      neoplasm. The syndrome is characterized by progressive amnesia and psychiatric
      disturbances resulting from an inflammatory reaction probably related to an
      immune response to the neuronal proteins expressed by tumors. It is usually
      associated with small cell lung cancer. In other cases, testicular cancer occurs
      more frequently than expected. Cranial magnetic resonance imaging may show
      increased signal intensity in the limbic cortex. Genitourinary examinations are
      sometimes inadequate. Testicular ultrasonography is recommended if no tumor is
      detected on the chest and abdominal computed tomography scan. The outcome of the
      treatment of the testicular cancer on the paraneoplastic syndrome is variable.

PMID- 11445491
TI  - Ureteropelvic junction obstruction due to inflammatory pseudotumor masquerading
      as hydronephrosis because of a neuropathic bladder in a child with
      myelomeningocele.
AB  - Inflammatory pseudotumors (IPTs), also known as inflammatory myofibroblastic
      tumors, are rare solid lesions, generally thought to be benign, which have been
      described in a variety of locations. We report a case of a child with a
      neuropathic bladder who developed a pseudotumor of the retroperitoneum that
      caused progressive ureteral obstruction distal to the ureteropelvic junction.
      Hydronephrosis as a complication of IPTs has been described with bladder and
      uterine IPTs; however, in our review of published reports, we found no reported
      cases of a retroperitoneal IPT causing proximal ureteral obstruction in a
      pediatric patient.

PMID- 11445492
TI  - Renal artery pseudoaneurysm occurring after partial nephrectomy.
AB  - Retroperitoneal hemorrhage resulting from intrarenal pseudoaneurysm formation has
      been reported after percutaneous renal surgery. However, although hemorrhage is a
      well-recognized complication of partial nephrectomy, hemorrhage caused by an
      intrarenal pseudoaneurysm after open partial nephrectomy is rare. We report a
      case of retroperitoneal hematoma associated with a renal artery pseudoaneurysm
      occurring in a 56-year-old woman 2.5 weeks after she underwent left partial
      nephrectomy for renal cell carcinoma. The pseudoaneurysmal branch was
      successfully identified and selectively embolized using percutaneous renal
      arterial angiography.

PMID- 11445493
TI  - Extramammary Paget's disease of scrotum.
AB  - We describe 4 cases of extramammary Paget's disease of the scrotum with
      underlying invasive carcinoma from 1997 to 1999. Three patients had metastatic
      inguinal lymphadenopathy. The delay in diagnosis was significant (mean 1 year).
      The diagnosis was made by skin biopsy in all patients. Histologically,
      intraepidermal cells with enlarged vesicular nuclei and vacuolated cytoplasm,
      which was mucin positive, were found. The mainstay of treatment is wide surgical
      excision, but positive margins remain a major problem. Other modes of treatment
      have been advocated but the efficacy for invasive disease is low. The key to
      successful control of the disease is therefore a high index of suspicion and
      early diagnosis.

PMID- 11445494
TI  - Estramustine-related hypocalcemia in patients with prostate carcinoma and
      osteoblastic metastases.
AB  - We describe a patient with androgen-independent prostate cancer in whom
      hypocalcemia developed during treatment with estramustine. The patient's total
      serum calcium level before and after the initiation of estramustine was 8.3 and
      4.3 mg/dL, respectively (normal range 8.4 to 10.2). This finding prompted us to
      review the calcium levels in 135 consecutive patients who were also undergoing
      treatment with a similar estramustine-containing regimen. We found that
      hypocalcemia had developed in 20% of these patients during treatment. We
      speculate that estramustine may cause hypocalcemia by inhibiting the mobilization
      of calcium and the action of the parathyroid hormone in the skeleton.

PMID- 11445495
TI  - Verrucous carcinoma of the renal pelvis.
AB  - We report a case of a verrucous carcinoma of the renal pelvis after a long
      history of a renal pelvis stone. Only 1 case of verrucous carcinoma of the renal
      pelvis has been previously reported, and ours is the first case not associated
      with a horseshoe kidney.

PMID- 11445496
TI  - Von Recklinghausen neurofibromatosis with urinary bladder involvement.
AB  - von Recklinghausen neurofibromatosis is an autosomal dominant transmitted disease
      with 100% penetrance but variable phenotypic expression. The incidence of this
      systemic disease is 1 in 3000 live births; however, genitourinary manifestations
      are rare. We report on our management of 1 case during the past 16 years.

PMID- 11445497
TI  - Metastatic adenocarcinoma of the prostate to the uvea as the initial presenting
      symptom in a 49-year-old man.
AB  - We report a case of a 49-year-old man who presented with symptoms related to his
      right eye. Subsequent workup revealed carcinoma of the prostate metastatic to the
      uvea. On ophthalmologic evaluation, choroidal metastasis was noted. His prostate
      was firm on digital rectal examination, and the serum prostate-specific antigen
      level was 124 ng/mL. Prostate biopsy was consistent with adenocarcinoma, Gleason
      score 9. The patient was treated with total androgen blockade and radiation to
      the eye. Although his ocular lesions disappeared, the patient died of hormone
      refractory disease 32 months after the diagnosis. The first case of prostate
      cancer metastatic to the uvea was reported more than 1 century ago; however, only
      a few cases have been reported subsequently. To our knowledge, we present the
      first published report in the urological literature of a patient in whom ocular
      complaints were the presenting symptoms that led to the diagnosis of prostate
      cancer. The urologist should be cognizant of the distinct possibility of ocular
      metastasis if a patient with prostate cancer presents with complaints related to
      the eye.

PMID- 11445498
TI  - Extensive lymphatic malformation of penis and scrotum.
AB  - Lymphangioma circumscriptum is an uncommon condition of the skin and subcutaneous
      tissues characterized by localized patches of vesicles. The penoscrotal region is
      a rare site for its development. We present a case with an extensive onset of
      lymphatic malformation of the pubis and penoscrotal region that we treated with
      wide excision. Reconstruction was achieved with a split-thickness skin graft
      combined with residual scrotal skin advancement.

PMID- 11445499
TI  - Spontaneous thrombosis of an iatrogenic arteriovenous fistula of the kidney.
AB  - A 44-year-old woman underwent radial nephrotomy for a symptomatic stone in a
      caliceal diverticulum. Five days after an uneventful postoperative course of 1
      week, she presented with gross hematuria. Routine ultrasound demonstrated a
      hypoechoic lesion in the kidney; color-coded sonography revealed an arteriovenous
      fistula. The hematuria ended before the scheduled angiography to embolize the
      fistula was performed. Repeated color-coded sonography revealed spontaneous
      thrombosis of the lesion. The follow-up examination 6 months later confirmed
      these findings. As traumatic arteriovenous fistulas have a good chance of
      spontaneous closure, invasive treatment should be postponed for as long as
      possible.

PMID- 11445500
TI  - Oxytocinergic neurotransmission at the hippocampus in the central neural
      regulation of penile erection in the rat.
AB  - OBJECTIVES: To investigate whether there is an oxytocinergic neurotransmission at
      the hippocampus involved in the central regulation of penile erection in the rat.
      METHODS: Male adult Sprague-Dawley (n = 27) rats anesthetized with pentobarbital
      were used. A 26-gauge needle was inserted into the corpus cavernosum to measure
      the intracavernous pressure (ICP) and the systemic and mean arterial pressure and
      heart rate simultaneously. The following studies were performed: stereotaxic
      delivery of oxytocin acetate (3 pmol/100 nL) into the hippocampus; microinjection
      of a mixture of [d(CH(2))(5)-Tyr(Me)(2)-Orn(8)]-vasotocin (3 pmol/100 nL) and
      oxytocin (3 pmol/100 nL) into the hippocampus; injection of saline into the
      hippocampus; and intracavernous injection of oxytocin (3 pmol/100 microL). The
      ICP and hemodynamic parameters were monitored after each administration of the
      experimental agents. RESULTS: After administration of oxytocin into the
      hippocampus, a significant increase in the ICP occurred from resting (8.8 +/- 1.7
      mm Hg) to a peak at 49.6 +/- 12.5 mm Hg and persisted for 18.6 +/- 9.4 minutes
      after an onset latency of 500.0 +/- 389.7 seconds. However, no change in the ICP
      occurred after administration of [d(CH(2))(5)-Tyr(Me)(2)-Orn(8)]-vasotocin plus
      oxytocin into the hippocampus. In addition, no elevation of ICP occurred after
      administration of saline to the hippocampus or after intracavernous injection of
      oxytocin. CONCLUSIONS: The results demonstrate that administration of oxytocin
      into the hippocampus induces penile erection in the rat. However, concomitant
      administration of oxytocin and its antagonist was ineffective in eliciting penile
      erection. These observations suggest that oxytocinergic neurotransmission at the
      hippocampus may be involved in the central neural regulation of the penile
      erection in the rat.

PMID- 11445501
TI  - Assessment of murine bladder permeability with fluorescein: validation with
      cyclophosphamide and protamine.
AB  - OBJECTIVES: Bladder hyperpermeability should result in elevated blood levels of
      intravesically administered agents. Reabsorption from a hyperpermeable bladder
      should result in prolonged urinary excretion of an agent after parenteral
      administration. To test these hypotheses, urinary clearance and plasma levels of
      sodium fluorescein (NaF) were measured in mice before and during cyclophosphamide
      (CYP) and protamine-induced hemorrhagic cystitis. METHODS: To measure the plasma
      uptake of NaF from the bladder, 10 mg/mL NaF was instilled, either by catheter or
      retrograde urethral infusion, 15 minutes before retro-orbital or ventricular
      sampling. The plasma levels were measured 24 hours and 14 days after exposure to
      CYP 300 mg/kg or 15 minutes after instillation of protamine 10 mg/mL. Hourly
      urine concentrations were measured immediately after intraperitoneal
      administration of 10 mg/kg NaF. Pretreatment samples were compared with those
      obtained 24 hours after intraperitoneal administration of 300 mg/kg CYP. RESULTS:
      Urinary NaF excretion was delayed in CYP-exposed mice. A bi-exponential model
      provided an appropriate fit of the data, both before and after CYP
      administration. The plasma levels of NaF were significantly elevated at 24 hours
      and 14 days after CYP exposure when sampled by ventricular nick or retro
      orbitally. The median concentration of fluorescein in the protamine-treated mice
      was significantly higher than in the control mice. CONCLUSIONS: Fluorescein can
      be used to measure alterations in bladder permeability after bladder mucosal
      injury in mice. Urinary excretion of NaF is a bi-exponential process that is
      delayed after bladder mucosal injury, presumably because of increased mucosal
      permeability and resorption from the urine into the bloodstream.

PMID- 11445502
TI  - Effects of sildenafil citrate, acetylcholine, and sodium nitroprusside on the
      relaxation of rabbit cavernosal tissue in vitro.
AB  - OBJECTIVES: To investigate the effect of sildenafil together with the influence
      of sodium nitroprusside and acetylcholine and further discuss its mechanism of
      action in vitro. METHODS: Isolated strips of rabbit corpus cavernosum were
      stimulated isometrically with phenylephrine. Graded relaxations were induced
      using increasing concentrations of acetylcholine, sodium nitroprusside, and
      sildenafil alone and in combination. RESULTS: The agents all relaxed the rabbit
      corpus cavernosal strips in a dose-dependent manner. The inhibitory potentials of
      the test agents were ranked (from least inhibitory to most inhibitory) as
      follows: sildenafil, acetylcholine plus sildenafil, sodium nitroprusside, sodium
      nitroprusside plus sildenafil, acetylcholine. The presence of sodium
      nitroprusside in the medium reduced the median effective dose for the sildenafil
      induced relaxation of the cavernosal tissue from 3.65 x 10(-5) M to 2.73 x 10(-7)
      M, and the presence of acetylcholine reduced it to 9.79 x 10(-6) M. CONCLUSIONS:
      Sildenafil enhances the relaxing effect of both sodium nitroprusside and
      acetylcholine on the phenylephrine-induced contraction of rabbit cavernosal
      tissue.

PMID- 11445503
TI  - In vivo selection of Pseudomonas Aeruginosa with decreased susceptibilities to
      fluoroquinolones during fluoroquinolone treatment of urinary tract infection.
AB  - OBJECTIVES: To present a case of fluoroquinolone treatment failure in urinary
      tract infection caused by Pseudomonas aeruginosa, accompanied by in vivo
      selection of the post-treatment isolate that showed decreased susceptibilities to
      fluoroquinolones, and to report fluoroquinolone resistance mechanisms in the post
      treatment isolate. METHODS: A patient with urinary tract infection was treated
      with a suboptimal dose of a fluorinated quinolone, gatifloxacin. P. aeruginosa
      strains were isolated before and after fluoroquinolone treatment. The
      pretreatment and post-treatment isolates were examined for relatedness by
      arbitrarily primed polymerase chain reaction. For these isolates, the minimum
      inhibitory concentration of antimicrobial agents was determined and mutations in
      the target genes (gyrA and parC) and regulatory genes (mexR and nfxB) for drug
      efflux pumps were analyzed. RESULTS: Failure of fluoroquinolone treatment of
      urinary tract infection was observed. The post-treatment isolate, which was
      assumed to be isogenic to the pretreatment isolate, exhibited fourfold to 16-fold
      increases in the MIC of fluoroquinolones. In this isolate, a new mutation, not
      observed in the pretreatment isolate, was found only in the gyrA gene, resulting
      in an amino acid change of aspartic acid to asparagine in codon 87 of GyrA.
      CONCLUSIONS: The P. aeruginosa isolate that was initially susceptible to
      fluoroquinolones showed decreased susceptibility to fluoroquinolones after
      treatment with a suboptimal dose of one fluoroquinolone. In the post-treatment
      isolate, the alteration of GyrA would be responsible for the decreased
      susceptibility to fluoroquinolones. We should be aware that inappropriate use of
      fluoroquinolones could select such a strain harboring a quinolone resistance
      associated alteration of DNA gyrase.

PMID- 11445504
TI  - John Clark, M.D: the first trained lithotomist in Colonial New England.

PMID- 11445505
TI  - Acting on an environmental health disaster: the case of the Aral Sea.
AB  - The Aral Sea area in Central Asia has been encountering one of the world's
      greatest environmental disasters for more than 15 years. During that time,
      despite many assessments and millions of dollars spent by large, multinational
      organizations, little has changed. The 5 million people living in this neglected
      and virtually unknown part of the world are suffering not only from an
      environmental catastrophe that has no easy solutions but also from a litany of
      health problems. The region is often dismissed as a chronic problem where nothing
      positive can be achieved. Within this complicated context, Medecins Sans
      Frontieres, winner of the Nobel Peace Prize in 1999, is actively trying to assess
      the impact of the environmental disaster on human health to help the people who
      live in the Aral Sea area cope with their environment. Medecins Sans Frontieres
      has combined a direct medical program to improve the health of the population
      while conducting operational research to gain a better understanding of the
      relationship between the environmental disaster and human health outcomes. In
      this paper we explore the health situation of the region and the broader policy
      context in which it is situated, and present some ideas that could potentially be
      applied to many other places in the world that are caught up in environmental and
      human health disasters.

PMID- 11445506
TI  - Residential water source and the risk of childhood brain tumors.
AB  - Gestation may represent a window of susceptibility to transplacental effects of
      environmental exposures, including chemicals in water. The N-nitroso compounds
      (NNC), a class of chemicals with demonstrated neurocarcinogenic potential,
      include substances detected in drinking water. We used data from a study of
      possible risk factors for childhood brain tumors (CBT) to investigate the
      association of source of residential drinking water during pregnancy and CBT
      occurrence among offspring. In addition, dipstick measurements were made of
      nitrates and nitrites in tap water for the subset of women living in the same
      home they had lived in during their pregnancies. Population-based CBT cases (n =
      540) and controls (n = 801) were identified in three regions including Los
      Angeles County, and the San Francisco Bay Area of California, and the Seattle
      Puget Sound area of western Washington state. Overall, we observed no increased
      risk of CBT in offspring associated with wells as the source of residential
      water. However, an increased risk of CBT [odds ratio (OR) = 2.6; 95% confidence
      interval (CI), = 1.3-5.2] was observed in western Washington among offspring of
      women who relied exclusively on well water, and a decreased risk of CBT (OR =
      0.2; 95% CI, 0.1-0.8) was observed in Los Angeles County. Among the small subset
      of subjects for whom dipstick measurements of tap water were available, the risk
      of CBT associated with the presence of either measurable nitrite and/or nitrate
      was 1.1 (95% CI, 0.7-2.0). Given the crude measurement method employed and
      because measurements often were obtained years after these pregnancies occurred,
      the relevance of the dipstick findings is unclear. The lack of consistency in our
      findings related to residential water source does not support the hypothesis of
      increased risk related to consumption of well water; however, regional
      differences in well water content may exist, and the increased risk observed in
      western Washington deserves further evaluation.

PMID- 11445507
TI  - Fetal growth and length of gestation in relation to prenatal exposure to
      environmental tobacco smoke assessed by hair nicotine concentration.
AB  - We assessed the effects of prenatal exposure to environmental tobacco smoke on
      fetal growth and length of gestation. The study population consisted of 389
      nonsmoking women who were selected from a population-based study in southeast
      Finland on the basis of questionnaire information after delivery (response rate
      94%). The final exposure assessment was based on nicotine concentration of
      maternal hair sampled after the delivery, which measures exposure during the past
      2 months (i.e., the third trimester). The exposure categories were defined a
      priori as high (nicotine concentration [Greater and equal to] 4.00 microg/g; n =
      52), medium (0.75 to < 4.00 microg/g; n = 186), and low as the reference category
      (< 0.75 microg/g; n = 151). In logistic regression analysis, controlling for
      confounding, the risk of preterm delivery (< 37 weeks) was higher in the high
      [adjusted odds ratio (OR) = 6.12; 95% confidence interval (CI), 1.31-28.7] and
      medium exposure categories (adjusted OR = 1.30; 95% CI, 0.30-5.58) compared with
      the reference category, and there was a 1.22 (95% CI, 1.07-1.39) increase in
      adjusted OR with a 1 microg/g increase in hair nicotine concentration. The
      corresponding adjusted OR was 1.06 (95% CI, 0.96-1.17) for low birth weight and
      1.04 (95% CI, 0.92-1.19) for small-for-gestational-age.

PMID- 11445508
TI  - Blood lead levels of primary school children in Dhaka, Bangladesh.
AB  - Dhaka, Bangladesh, has one of the highest air lead levels in the world. In
      February 2000, we evaluated children at five primary schools in Dhaka to
      determine blood lead (BPb) levels, sources of environmental exposure, and
      potential risk factors for lead poisoning. Selected schools represented a range
      of geographic and socioeconomic strata. A total of 779 students 4-12 years of age
      participated. The mean BPb level was 15.0 microg/dL (range 4.2-63.1 microg/dL).
      Most students (87.4%) had BPb levels above the Centers for Disease Control and
      Prevention's level of concern (10 microg/dL). Elevated BPb levels correlated with
      soil eating [odds ratio (OR) = 3.31; 95% confidence interval (CI), 1.30-8.39],
      low parental education (OR = 2.72; 95% CI, 1.97-3.75), living close to major
      roads (OR = 2.30; 95% CI, 1.23-4.29), and increasing age (OR = 1.11; 95% CI, 1.06
      1.16). BPb levels measured were similar to those in other countries that use
      leaded gasoline. No other potential sources of lead exposure were consistently
      identified. Combustion of leaded gasoline is the main source of lead exposure in
      Dhaka, resulting in ubiquitous contamination of the environment. The increase in
      BPb levels with age, a finding contrary to observations in the United States and
      Australia, may be related to increased outdoor activities. The Bangladeshi
      government recently announced a plan to eliminate leaded gasoline. Baseline BPb
      surveys are critical to develop and evaluate intervention policies. Strategies to
      reduce BPb levels need to address variations in socioeconomic status,
      construction type and location of housing, and levels of hygiene.

PMID- 11445509
TI  - Consultations of children living near open-cast coal mines.
AB  - Because of local concerns, general practitioner consultation rates in children
      living in communities close to and away from open-cast mines were compared.
      Information on consultations was collected on 2,442 children 1-11 years of age
      living in five socioeconomically matched pairs of open-cast and control
      communities in northern England. The data collection periods were 6 weeks each
      during 1996-1997 and the 52-week periods preceding these weeks. Consultations
      were categorized as respiratory, skin and eye conditions (possibly exacerbated by
      particulate matter), or other conditions. Over the 6-week periods, children in
      4/5 pairs of open-cast and control communities had similar consultation rates for
      all conditions combined [2.7 vs. 2.4 per person-year; odds ratio (OR) = 1.1; 95%
      confidence interval (CI), 0.96-1.3). Consultations were higher in the open-cast
      communities for respiratory, skin, and eye conditions (2.1 vs. 1.5 per person
      year; OR = 1.4; 95% CI, 1.2-1.7), and respiratory conditions alone (1.5 vs. 1.1
      per person-year; OR = 1.5; 95% CI, 1.2-1.8). However, increases in consultation
      rates in open-cast communities were generally not seen over the portions of the
      52-week periods when the open-cast sites were either active or inactive.

PMID- 11445510
TI  - Helicobacter pylori prevalences and risk factors among school beginners in a
      German urban center and its rural county.
AB  - In 1998, the Helicobacter pylori [(13)C]urea breath test was offered to all
      school beginners (birth cohort 1991/1992) in the city of Leipzig and in Leipzig
      County, Germany, to determine the colonization prevalence and potential
      transmission pathways of the bacterium. A total of 3,347 school beginners
      participated in the test, and 2,888 parents completed the detailed, self
      administered questionnaire. The H. pylori prevalence was 6.5% [95% confidence
      interval (CI), 5.3-7.6] in the city and 5.7% (CI, 4.2-7.0) in the county. Using
      cluster analysis (WARD's method, Euclidean distances), we identified different
      sets of variables (confirmed by multivariate logistic regression analyses [odds
      ratios (ORs)] that are signficantly associated with H. pylori positivity. Among
      city children, the risk is significantly increased with contact to a pet hamster
      (OR = 2.4; 95% CI, 1.2-4.7; p < 0.015) and travels to Asian countries (OR = 3.7;
      95% CI, 1.6-8.7; p < 0.002). Among county children, H. pylori positivity
      increased significantly with drinking of water from nonmunicipal sources (OR =
      16.4; 95% CI, 3.1-88.5; p < 0.001), more than 3 children living in a household
      (OR = 4.2; 95% CI, 1.2-14.6; p < 0.02), and contact with pet hamsters (OR = 2.4;
      95% CI, 1.0-5.7; p < 0.04). These data suggest that, in a general population
      sample, indirect fecal-oral transmission and living conditions are important risk
      factors in the spread of H. pylori infection. However, clinical symptoms do not
      necessarily indicate H. pylori positivity.

PMID- 11445511
TI  - Environmental tobacco smoke, parental atopy, and childhood asthma.
AB  - We hypothesized that the joint effect of genetic propensity to asthma and
      exposure to environmental tobacco smoke on the risk of childhood asthma is
      greater than expected on the basis of their independent effects. We performed a
      population-based 4-year cohort study of 2,531 children born in Oslo, Norway. We
      collected information on the child's health and environmental exposures at birth
      and when the child was 6, 12, 18, and 24 months and 4 years of age. The outcomes
      of interest were bronchial obstruction during the first 2 years and asthma at the
      age of 4 years. Parental atopy was defined as a history of maternal or paternal
      asthma or hay fever. Exposure to environmental tobacco smoke was defined on the
      basis of questionnaire information on household smokers at birth. In logistic
      regression analysis adjusting for confounding, parental atopy alone increased the
      risk of bronchial obstruction [odds ratio 1.62; 95% confidence interval (CI) 1.10
      2.40] and asthma (1.66; 95% CI, 1.08-2.54). In children without parental atopy,
      there was little effect of exposure to environmental tobacco smoke on bronchial
      obstruction (1.29; 95% CI, 0.88-1.89) and asthma (0.84; 95% CI, 0.53-1.34). The
      presence of parental atopy and exposure had a substantial effect both on
      bronchial obstruction (2.88; 95% CI, 1.91-4.32) and asthma (2.68; 95% CI, 1.70
      4.22). The results are consistent with the hypothesized joint effect of parental
      atopy and exposure to environmental tobacco smoke. This phenomenon--denoted as
      effect modification of environmental exposure by genetic constitution, or gene by
      environment interaction--suggests that some genetic markers could indicate
      susceptibility to environmental factors.

PMID- 11445512
TI  - Measurement of children's exposure to pesticides: analysis of urinary metabolite
      levels in a probability-based sample.
AB  - The Minnesota Children's Pesticide Exposure Study is a probability-based sample
      of 102 children 3-13 years old who were monitored for commonly used pesticides.
      During the summer of 1997, first-morning-void urine samples (1-3 per child) were
      obtained for 88% of study children and analyzed for metabolites of insecticides
      and herbicides: carbamates and related compounds (1-NAP), atrazine (AM),
      malathion (MDA), and chlorpyrifos and related compounds (TCPy). TCPy was present
      in 93% of the samples, whereas 1-NAP, MDA, and AM were detected in 45%, 37%, and
      2% of samples, respectively. Measured intrachild means ranged from 1.4 microg/L
      for MDA to 9.2 microg/L for TCPy, and there was considerable intrachild
      variability. For children providing three urine samples, geometric mean TCPy
      levels were greater than the detection limit in 98% of the samples, and nearly
      half the children had geometric mean 1-NAP and MDA levels greater than the
      detection limit. Interchild variability was significantly greater than intrachild
      variability for 1-NAP (p = 0.0037) and TCPy (p < 0.0001). The four metabolites
      measured were not correlated within urine samples, and children's metabolite
      levels did not vary systematically by sex, age, race, household income, or
      putative household pesticide use. On a log scale, mean TCPy levels were
      significantly higher in urban than in nonurban children (7.2 vs. 4.7 microg/L; p
      = 0.036). Weighted population mean concentrations were 3.9 [standard error (SE) =
      0.7; 95% confidence interval (CI), 2.5, 5.3] microg/L for 1-NAP, 1.7 (SE = 0.3;
      95% CI, 1.1, 2.3) microg/L for MDA, and 9.6 (SE = 0.9; 95% CI, 7.8, 11) microg/L
      for TCPy. The weighted population results estimate the overall mean and
      variability of metabolite levels for more than 84,000 children in the census
      tracts sampled. Levels of 1-NAP were lower than reported adult reference range
      concentrations, whereas TCPy concentrations were substantially higher.
      Concentrations of MDA were detected more frequently and found at higher levels in
      children than in a recent nonprobability-based sample of adults. Overall,
      Minnesota children's TCPy and MDA levels were higher than in recent population
      based studies of adults in the United States, but the relative magnitude of
      intraindividual variability was similar for adults and children.

PMID- 11445513
TI  - Atmospheric circulation types and daily mortality in Athens, Greece.
AB  - We investigated the short-term effects of synoptic and mesoscale atmospheric
      circulation types on mortality in Athens, Greece. The synoptic patterns in the
      lower troposphere were classified in 8 a priori defined categories. The mesoscale
      weather types were classified into 11 categories, using meteorologic parameters
      from the Athens area surface monitoring network; the daily number of deaths was
      available for 1987-1991. We applied generalized additive models (GAM), extending
      Poisson regression, using a LOESS smoother to control for the confounding effects
      of seasonal patterns. We adjusted for long-term trends, day of the week, ambient
      particle concentrations, and additional temperature effects. Both
      classifications, synoptic and mesoscale, explain the daily variation of mortality
      to a statistically significant degree. The highest daily mortality was observed
      on days characterized by southeasterly flow [increase 10%; 95% confidence
      interval (CI), 6.1-13.9% compared to the high-low pressure system), followed by
      zonal flow (5.8%; 95% CI, 1.8-10%). The high-low pressure system and the
      northwesterly flow are associated with the lowest mortality. The seasonal
      patterns are consistent with the annual pattern. For mesoscale categories, in the
      cold period the highest mortality is observed during days characterized by the
      easterly flow category (increase 9.4%; 95% CI, 1.0-18.5% compared to flow without
      the main component). In the warm period, the highest mortality occurs during the
      strong southerly flow category (8.5% increase; 95% CI, 2.0-15.4% compared again
      to flow without the main component). Adjusting for ambient particle levels leaves
      the estimated associations unchanged for the synoptic categories and slightly
      increases the effects of mesoscale categories. In conclusion, synoptic and
      mesoscale weather classification is a useful tool for studying the weather-health
      associations in a warm Mediterranean climate situation.

PMID- 11445514
TI  - Assessing exposure to disinfection by-products in women of reproductive age
      living in Corpus Christi, Texas, and Cobb county, Georgia: descriptive results
      and methods.
AB  - We conducted a field study in Corpus Christi, Texas, and Cobb County, Georgia, to
      evaluate exposure measures for disinfection by-products, with special emphasis on
      trihalomethanes (THMs). Participants were mothers living in either geographic
      area who had given birth to healthy infants from June 1998 through May 1999. We
      assessed exposure by sampling blood and water and obtaining information about
      water use habits and tap water characteristics. Two 10-mL whole blood samples
      were collected from each participant before and immediately after her shower.
      Levels of individual THM species (chloroform, bromodichloromethane,
      dibromochloromethane, and bromoform) were measured in whole blood [parts per
      trillion (pptr)] and in water samples (parts per billion). In the Corpus Christi
      water samples, brominated compounds accounted for 71% of the total THM
      concentration by weight; in Cobb County, chloroform accounted for 88%.
      Significant differences in blood THM levels were observed between study
      locations. For example, the median baseline blood level of bromoform was 0.3 pptr
      and 3.5 pptr for participants in Cobb County and Corpus Christi, respectively (p
      = 0.0001). Differences were most striking in blood obtained after showering. For
      bromoform, the median blood levels were 0.5 pptr and 17 pptr for participants in
      Cobb County and Corpus Christi, respectively (p = 0.0001). These results suggest
      that blood levels of THM species vary substantially across populations, depending
      on both water quality characteristics and water use activities. Such variation
      has important implications for epidemiologic studies of the potential health
      effects of disinfection by-products.

PMID- 11445515
TI  - Impairments of memory and learning in older adults exposed to polychlorinated
      biphenyls via consumption of Great Lakes fish.
AB  - An association between in utero polychlorinated biphenyl (PCB) exposure and
      impaired childhood intellectual functioning has been reported, but the potential
      impact of PCB exposure during adulthood on intellectual functioning has received
      little attention. We assessed the impact of PCBs and other fish-borne
      contaminants on intellectual functioning in older adults. The subjects were 49-
      to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters
      ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate <
      6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests
      of memory and learning, executive function, and visual-spatial function was
      administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood
      samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive
      outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene
      (DDE) were markedly elevated in fish eaters. After controlling for potential
      confounders PCB, but not DDE, exposure was associated with lower scores on
      several measures of memory and learning. These included the Weschler Memory Scale
      verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and
      list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In
      contrast, executive and visual-spatial function were not impaired by exposure to
      either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated
      with impairments in memory and learning, whereas executive and visual-spatial
      function were unaffected. These results are consistent with previous research
      showing an association between in utero PCB exposure and impairments of memory
      during infancy and childhood.

PMID- 11445516
TI  - Oral succimer decreases the gastrointestinal absorption of lead in juvenile
      monkeys.
AB  - Although succimer (Chemet, meso-2,3-dimercaptosuccinic acid, DMSA) is considered
      to be a safe and effective chelating agent for the treatment of lead poisoning in
      humans, there is concern that it may increase the gastrointestinal (GI)
      absorption and retention of Pb from exposures suffered concurrent with treatment.
      This concern is justified because the availability of Pb-safe housing during
      outpatient treatment with oral succimer is limited. We used a juvenile nonhuman
      primate model of moderate childhood Pb intoxication and a sensitive double stable
      Pb isotope tracer methodology to determine whether oral succimer chelation
      affects the GI absorption and whole-body retention of Pb. Infant rhesus monkeys
      (n = 17) were exposed to Pb daily for 1 year postpartum to reach and maintain a
      target blood lead (BPb) level of 35-40 microg/dL. Animals were administered
      succimer (n = 9) or vehicle (n = 8) over two successive 19 day succimer treatment
      regimens beginning at 53 and 65 weeks of age. The present study was conducted
      over the second chelation regimen only. Animals received a single intravenous
      (iv) dose of stable (204)Pb tracer (5 microg, 24.5 nmol) followed by a single
      oral dose of stable (206)Pb tracer (72.6 microg, 352 nmol) immediately before
      chelation, in order to specifically evaluate GI Pb absorption and whole-body Pb
      retention with treatment. We collected complete urine and fecal samples over the
      first 5 days and whole blood over the first 8 days of treatment for analyses of
      stable Pb isotopes using magnetic sector inductively-coupled plasma mass
      spectrometry. Results indicate that succimer significantly reduced the GI
      absorption of Pb (vehicle, 64.9% +/- 5.5; succimer, 37.0% +/- 5.8; mean +/- SEM).
      Succimer also significantly increased the urinary excretion of endogenous Pb by
      approximately 4-fold over the vehicle treatment, while endogenous fecal Pb
      excretion was decreased by approximately 33%. Finally, although succimer reduced
      the whole-body retention of endogenous Pb by approximately 10% compared to
      vehicle, the majority (77%) of the administered internal dose of Pb tracer was
      retained in the body when assessed after 5 days of treatment. These data do not
      support the concern that succimer treatment increases GI Pb absorption.

PMID- 11445517
TI  - Altered operant responding for motor reinforcement and the determination of
      benchmark doses following perinatal exposure to low-level 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180
      ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation.
      Their adult female offspring were trained to respond on a lever for brief
      opportunities to run in specially designed running wheels. Once they had begun
      responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio
      requirement for lever pressing was increased at five-session intervals to values
      of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each
      behavior session to track estrous cyclicity. Under each of the FR values,
      perinatal TCDD exposure produced a significant dose-related reduction in the
      number of earned opportunities to run, the lever response rate, and the total
      number of revolutions in the wheel. Estrous cyclicity was not affected. Because
      of the consistent dose-response relationship at all FR values, we used the
      behavioral data to calculate benchmark doses based on displacements from modeled
      zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a
      quadratic fit to the dose-response function. The mean ED(10) benchmark dose for
      earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg.
      The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The
      mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95%
      lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95%
      lower bound of 0.60. These values should be viewed from the perspective of
      current human body burdens, whose average value, based on TCDD toxic equivalents,
      has been calculated as 13 ng/kg.

PMID- 11445518
TI  - Arsenic in drinking water and pregnancy outcomes.
AB  - We studied a group of women of reproductive age (15-49 years) who were
      chronically exposed to arsenic through drinking water to identify the pregnancy
      outcomes in terms of live birth, stillbirth, spontaneous abortion, and preterm
      birth. We compared pregnancy outcomes of exposed respondents with pregnancy
      outcomes of women of reproductive age (15-49 years) who were not exposed to
      arsenic-contaminated water. In a cross-sectional study, we matched the women in
      both exposed and nonexposed groups for age, socioeconomic status, education, and
      age at marriage. The total sample size was 192, with 96 women in each group
      (i.e., exposed and nonexposed). Of the respondents in the exposed group, 98% had
      been drinking water containing [Greater and equal to] 0.10 mg/L arsenic and 43.8%
      had been drinking arsenic-contaminated water for 5-10 years. Skin manifestation
      due to chronic arsenic exposure was present in 22.9% of the respondents. Adverse
      pregnancy outcomes in terms of spontaneous abortion, stillbirth, and preterm
      birth rates were significantly higher in the exposed group than those in the
      nonexposed group (p = 0.008, p = 0.046, and p = 0.018, respectively).

PMID- 11445519
TI  - Using geographic information systems to assess individual historical exposure to
      air pollution from traffic and house heating in Stockholm.
AB  - A specific aim of a population-based case-control study of lung cancer in
      Stockholm, Sweden, was to use emission data, dispersion models, and geographic
      information systems (GIS) to assess historical exposure to several components of
      ambient air pollution. Data collected for 1,042 lung cancer cases and 2,364
      population controls included information on residence from 1955 to the end of
      follow-up for each individual, 1990-1995. We assessed ambient air concentrations
      of pollutants from road traffic and heating throughout the study area for three
      points in time (1960, 1970, and 1980) using reconstructed emission data for the
      index pollutants nitrogen oxides (NO(x)/NO(2)) and sulfur dioxide together with
      dispersion modeling. NO(2) estimates for 1980 compared well with actual
      measurements, but no independently measured (study-external) data were available
      for SO(2), precluding similar validation. Subsequently, we used linear intra- and
      extrapolation to obtain estimates for all other years 1955-1990. Eleven thousand
      individual addresses were transformed into geographic coordinates through
      automatic and manual procedures, with an estimated error of < 100 m for 90% of
      the addresses. Finally, we linked annual air pollution estimates to annual
      residence coordinates, yielding long-term residential exposure indices for each
      individual. There was a wide range of individual long-term average exposure, with
      an 11-fold interindividual difference in NO(2) and an 18-fold difference in
      SO(2). The 30-year average for all study subjects was 20 microg/m(3) NO(2) from
      traffic and 53 microg/m(3) SO(2) from heating. The results indicate that GIS can
      be useful for exposure assessment in environmental epidemiology studies, provided
      that detailed geographically related exposure data are available for relevant
      time periods.

PMID- 11445520
TI  - Bioaerosol lung damage in a worker with repeated exposure to fungi in a water
      damaged building.
AB  - There has been increased concern over health effects related to potential
      exposure of building occupants to bioaerosols. We report the case of a worker
      with a respiratory illness related to bioaerosol exposure in a water-damaged
      building with extensive fungal contamination. We performed environmental tests to
      evaluate potential exposure to fungi, and we used mycotoxin-specific IgG antibody
      in serologic studies in the attempt to evaluate exposure to mycotoxins. Extensive
      fungal contamination was documented in many areas of the building. Penicillium,
      Aspergillus, and Stachybotrys species were the most predominant fungi found in
      air sampling. Our serologic test was not useful in differentiating workers who
      were probably occupationally exposed to mycotoxins from those who were not;
      however, it did yield evidence that individuals may make specific IgG antibodies
      to macrocyclic tricothecene mycotoxins. Further research is needed concerning
      health effects related to bioaerosol exposures, particularly regarding markers of
      exposure to specific fungi that may produce mycotoxins. In the absence of
      clinical tools specific for evaluation of mycotoxin-related illness, a systematic
      clinical approach for evaluating persons with suspected building-related
      respiratory illness is warranted.

PMID- 11445521
TI  - It's time to rethink dose: the case for combining cancer and birth and
      developmental defects.

PMID- 11445522
TI  - Chromium(III) and DNA damage.

PMID- 11445523
TI  - Sex ratios at birth as monitors of endocrine disruption.

PMID- 11445525
TI  - Last call for Lindane.

PMID- 11445526
TI  - Green lessons boost grades.

PMID- 11445527
TI  - Dirty air stunts lung growth.

PMID- 11445528
TI  - Uncovering the viral mechanics of croup.

PMID- 11445529
TI  - NIEHS investigates links between children, the environment, and neurotoxicity.

PMID- 11445530
TI  - NTP center reports on phthalate concerns.

PMID- 11445531
TI  - Caution--children at play: how dangerous is CCA?

PMID- 11445532
TI  - A growth spurt in children's health laws.

PMID- 11445533
TI  - Special treatment: disposing of CCA-treated wood.

PMID- 11445534
TI  - Internal ribosome entry sites in eukaryotic mRNA molecules.

PMID- 11445535
TI  - The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional
      repressor.
AB  - We describe a novel mammalian DNA binding activity that requires at least two
      symmetrically methylated CpG dinucleotides in its recognition sequence,
      preferably within the sequence 5'CGCG. A key component of the activity is Kaiso,
      a protein with POZ and zinc-finger domains that is known to associate with p120
      catenin. We find that Kaiso behaves as a methylation-dependent transcriptional
      repressor in transient transfection assays. Kaiso is a constituent of one of two
      methyl-CpG binding complexes originally designated as MeCP1. The data suggest
      that zinc-finger motifs are responsible for DNA binding, and may therefore target
      repression to specific methylated regions of the genome. As Kaiso associates with
      p120 catenin, Kaiso may link events at the cell surface with DNA methylation
      dependent gene silencing.

PMID- 11445536
TI  - The ATM-related domain of TRRAP is required for histone acetyltransferase
      recruitment and Myc-dependent oncogenesis.
AB  - The ATM-related TRRAP protein is a component of several different histone
      acetyltransferase (HAT) complexes but lacks the kinase activity characteristic of
      other ATM family members. We identified a novel function for this evolutionarily
      conserved domain in its requirement for the assembly of a functional HAT complex.
      Ectopic expression of TRRAP protein with a mutation in the ATM-related domain
      inhibits Myc-mediated oncogenic transformation. The Myc-binding region of TRRAP
      maps to a separable domain, and ectopic expression of this domain inhibits cell
      growth. These findings demonstrate that the ATM-related domain of TRRAP forms a
      structural core for the assembly and recruitment of HAT complexes by
      transcriptional activators.

PMID- 11445537
TI  - Mzf1 controls cell proliferation and tumorigenesis.
AB  - MZF1 is a transcription factor belonging to the Kruppel family of zinc finger
      proteins, expressed in totipotent hemopoietic cells as well as in myeloid
      progenitors. Here we have inactivated Mzfi1 by gene targeting. Mzf1(-/-) mice
      develop lethal neoplasias characterized by the infiltration and complete
      disruption of the liver architecture by a monomorphic population of cells of
      myeloid origin reminiscent of human chloromas. Mzf1 inactivation results in a
      striking increase of the autonomous cell proliferation and of the ability of
      Mzf1(-/-) hemopoietic progenitors to sustain long-term hemopoiesis. These
      findings demonstrate that Mzf1 can act as a tumor/growth suppressor in the
      hemopoietic compartment.

PMID- 11445538
TI  - SOCS1 deficiency results in accelerated mammary gland development and rescues
      lactation in prolactin receptor-deficient mice.
AB  - Prolactin is essential for proliferation and differentiation of the developing
      mammary gland. We have explored a role for Suppressor of Cytokine Signaling 1
      (SOCS1) as a modulator of the prolactin response using mice deficient in SOCS1,
      which were rescued from neonatal death by deletion of the Interferon gamma (IFN
      gamma) gene. SOCS1(-/-)/IFN gamma(-/-) mice exhibited accelerated lobuloalveolar
      development in the mammary gland during late pregnancy and precocious lactation.
      Significantly, the lactogenic defect in prolactin receptor heterozygous females
      could be rescued by deletion of a single SOCS1 allele. These findings establish a
      role for SOCS1 as a negative regulator of prolactin signaling and suggest that
      SOCS1 is required for the prevention of lactation prior to parturition.

PMID- 11445539
TI  - Identification of novel small RNAs using comparative genomics and microarrays.
AB  - A burgeoning list of small RNAs with a variety of regulatory functions has been
      identified in both prokaryotic and eukaryotic cells. However, it remains
      difficult to identify small RNAs by sequence inspection. We used the high
      conservation of small RNAs among closely related bacterial species, as well as
      analysis of transcripts detected by high-density oligonucleotide probe arrays, to
      predict the presence of novel small RNA genes in the intergenic regions of the
      Escherichia coli genome. The existence of 23 distinct new RNA species was
      confirmed by Northern analysis. Of these, six are predicted to encode short ORFs,
      whereas 17 are likely to be novel functional small RNAs. We discovered that many
      of these small RNAs interact with the RNA-binding protein Hfq, pointing to a
      global role of the Hfq protein in facilitating small RNA function. The approaches
      used here should allow identification of small RNAs in other organisms.

PMID- 11445540
TI  - Control of cell division by a retinoblastoma protein homolog in Chlamydomonas.
AB  - A key pathway that controls both cell division and differentiation in animal
      cells is mediated by the retinoblastoma (RB) family of tumor suppressors, which
      gate the passage of cells from G(1) to S and through S phase. The role(s) of the
      RB pathway in plants are not yet clearly defined, nor has there been any evidence
      for its presence in unicellular organisms. Here we have identified an RB homolog
      encoded by the mat3 gene in Chlamydomonas reinhardtii, a unicellular green alga
      in the land plant lineage. Chlamydomonas cells normally grow to many times their
      original size during a prolonged G(1) and then undergo multiple alternating
      rounds of S phase and mitosis to produce daughter cells of uniform size. mat3
      mutants produce small daughter cells and show defects in two size-dependent cell
      cycle controls: They initiate the cell cycle at a below-normal size, and they
      undergo extra rounds of S phase/mitosis. Unlike mammalian RB mutants, mat3
      mutants do not have a shortened G(1), do not enter S phase prematurely, and can
      exit the cell cycle and differentiate normally, indicating that the RB pathway in
      Chlamydomonas has a different role than in animals.

PMID- 11445541
TI  - Division site selection protein DivIVA of Bacillus subtilis has a second distinct
      function in chromosome segregation during sporulation.
AB  - DivIVA is a coiled-coil, tropomyosin-like protein of Gram-positive bacteria.
      Previous work showed that this protein is targeted to division sites and retained
      at the cell poles after division. In vegetative cells, DivIVA sequesters the
      MinCD division inhibitor to the cell poles, thereby helping to direct cell
      division to the correct midcell site. We now show that DivIVA has a second, quite
      separate role in sporulating cells of Bacillus subtilis. It again acts at the
      cell pole but in this case interacts with the chromosome segregation machinery to
      help position the oriC region of the chromosome at the cell pole, in preparation
      for polar division. We isolated mutations in divIVA that separate the protein's
      role in sporulation from its vegetative function in cell division. DivIVA
      therefore appears to be a bifunctional protein with distinct roles in division
      site selection and chromosome segregation.

PMID- 11445542
TI  - Nuclear reorganization and homologous chromosome pairing during meiotic prophase
      require C. elegans chk-2.
AB  - Analysis of mutants defective in meiotic chromosome pairing has uncovered a role
      for Caenorhabditis elegans chk-2 in initial establishment of pairing between
      homologous chromosomes during early meiotic prophase. chk-2 is also required for
      the major spatial reorganization of nuclei that normally accompanies the onset of
      pairing, suggesting a mechanistic coupling of these two events. Despite failures
      in pairing, nuclear reorganization, and crossover recombination, chk-2 mutants
      undergo many other aspects of meiotic chromosome morphogenesis and complete
      gametogenesis. Although chk-2 encodes a C. elegans ortholog of the Cds1/Chk2
      checkpoint protein kinases, germ-line nuclei in chk-2 mutants are competent to
      arrest proliferation in response to replication inhibition and to trigger DNA
      damage checkpoint responses to ionizing radiation. However, chk-2 mutants are
      defective in triggering the pachytene DNA damage checkpoint in response to an
      intermediate block in the meiotic recombination pathway, suggesting that chk-2 is
      required either for initiation of meiotic recombination or for monitoring a
      specific subset of DNA damage lesions. We propose that chk-2 functions during
      premeiotic S phase to enable chromosomes to become competent for subsequent
      meiotic prophase events and/or to coordinate replication with entry into
      prophase.

PMID- 11445543
TI  - Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin.
AB  - In skin, multipotent stem cells generate the keratinocytes of the epidermis,
      sebaceous gland, and hair follicles. In this paper, we show that Tcf3 and Lef1
      control these differentiation lineages. In contrast to Lef1, which requires Wnt
      signaling and stabilized beta-catenin to express the hair-specific keratin genes
      and control hair differentiation, Tcf3 can act independently of its beta-catenin
      interacting domain to suppress features of epidermal terminal differentiation, in
      which Tcf3 is normally shut off, and promote features of the follicle outer root
      sheath (ORS) and multipotent stem cells (bulge), the compartments which naturally
      express Tcf3. These aspects of Tcf3's action are dependent on its DNA binding and
      Groucho repressor-binding domains. In the absence of its beta-catenin interacting
      domain, Lef1's behavior (Delta NLef1) seems to be markedly distinct from that of
      Delta NTcf3. Delta NLef1 does not suppress epidermal differentiation and promote
      ORS/bulge differentiation, but rather suppresses hair differentiation and gives
      rise to sebocyte differentiation. Taken together, these findings provide powerful
      evidence that the status of Tcf3/Lef complexes has a key role in controlling cell
      fate lineages in multipotent skin stem cells.

PMID- 11445544
TI  - Tissue-specific deletion of Foxa2 in pancreatic beta cells results in
      hyperinsulinemic hypoglycemia.
AB  - We have used conditional gene ablation to uncover a dramatic and unpredicted role
      for the winged-helix transcription factor Foxa2 (formerly HNF-3 beta) in
      pancreatic beta-cell differentiation and metabolism. Mice that lack Foxa2
      specifically in beta cells (Foxa2(loxP/loxP); Ins.Cre mice) are severely
      hypoglycemic and show dysregulated insulin secretion in response to both glucose
      and amino acids. This inappropriate hypersecretion of insulin in the face of
      profound hypoglycemia mimics pathophysiological and molecular aspects of familial
      hyperinsulinism. We have identified the two subunits of the beta-cell ATP
      sensitive K(+) channel (K(ATP)), the most frequently mutated genes linked to
      familial hyperinsulinism, as novel Foxa2 targets in islets. The Foxa2(loxP/loxP);
      Ins.Cre mice will serve as a unique model to investigate the regulation of
      insulin secretion by the beta cell and suggest the human FOXA2 as a candidate
      gene for familial hyperinsulinism.

PMID- 11445545
TI  - The eyeless homeodomain is dispensable for eye development in Drosophila.
AB  - Pax-6 genes, known to be essential for eye development, encode an evolutionarily
      conserved transcription factor with two DNA-binding domains. To corroborate the
      contribution of each DNA-binding domain to eye formation, we generated truncated
      forms of the Drosophila Pax-6 gene eyeless and tested their capacity to rescue
      the ey(2) mutant. Surprisingly, EY deleted of the homeodomain rescued the ey(2)
      mutant and triggered ectopic eyes morphogenesis. In contrast, EY lacking the
      paired domain failed to rescue the ey(2) mutant, led to truncation of appendages,
      and repressed Distal-less when misexpressed. This result suggests distinct
      functions mediated differentially by the two DNA-binding domains of eyeless.

PMID- 11445546
TI  - Sphingolipid activator proteins: proteins with complex functions in lipid
      degradation and skin biogenesis.
AB  - Sphingolipid activator proteins (SAPs or saposins) are essential cofactors for
      the lysosomal degradation of membrane-anchored sphingolipids. Four of the five
      known proteins of this class, SAPs A--D, derive from a single precursor protein
      and show high homology, whereas the fifth protein, GM2AP, is larger and displays
      a different secondary structure. Although the main function of all five proteins
      is assumed to lie in the activation of lipid degradation, their specificities and
      modes of action seem to differ considerably. It has recently been demonstrated
      that the action of the proteins is highly enhanced by the presence of acidic
      lipids in the target membranes. These results have some interesting implications
      for the topology of lysosomal degradation of lipids and may provide new insights
      into the function of these interesting proteins, which are ubiquitously expressed
      in the different tissues of the body. Recent studies indicated that the SAPs play
      an important role in the biogenesis of the epidermal water barrier, which has
      been demonstrated by the analysis of the skin phenotype displayed by SAP-knockout
      mice. The results obtained so far have led to some new insights into the
      formation of the epidermal water permeability barrier and may lead to a better
      understanding of this complex process.

PMID- 11445547
TI  - Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans.
AB  - Heparanases are endoglycosidases that cleave the heparan sulfate
      glycosaminoglycans from proteoglycan core proteins and degrade them to small
      oligosaccharides. Inside cells, these enzymes are important for the normal
      catabolism of heparan sulfate proteoglycans (HSPGs), generating glycosaminoglycan
      fragments that are then transported to lysosomes and completely degraded. When
      secreted, heparanases are thought to degrade basement membrane HSPGs at sites of
      injury or inflammation, allowing extravasion of immune cells into nonvascular
      spaces and releasing factors that regulate cell proliferation and angiogenesis.
      Heparanases have been described in a wide variety of tissues and cells, but
      because of difficulties in developing simple assays to follow activity, very
      little has been known about enzyme diversity until recently. Within the last 10
      years, heparanases have been purified from platelets, placenta, and Chinese
      hamster ovary cells. Characterization of the enzymes suggests there may be a
      family of heparanase proteins with different substrate specificities and
      potential functions.

PMID- 11445548
TI  - Embryos of the sea urchin Strongylocentrotus purpuratus synthesize a dermatan
      sulfate enriched in 4-O- and 6-O-disulfated galactosamine units.
AB  - Unfertilized eggs of the sea urchin Strongylocentrotus purpuratus are surrounded
      by a gelatinous layer rich in sulfated fucan. Shortly after fertilization this
      polysaccharide disappears, but 24 h later the embryos synthesize high amounts of
      dermatan sulfate concomitantly with the mesenchyme blastula-early gastrula stage
      when the larval gut is forming. This glycosaminoglycan has the same backbone
      structure [4-alpha-L-IdoA-1-->3-beta-D-GalNAc-1](n) as the mammalian counterpart
      but possesses a different sulfation pattern. It has a high content of 4-O- and 6
      O-disulfated galactosamine units. In addition, chains of this dermatan sulfate
      are considerable longer than those of vertebrate tissues. Adult sea urchin
      tissues contain high concentrations of sulfated polysaccharides, but dermatan
      sulfate is restricted to the adult body wall where it accounts for approximately
      20% of the total sulfated polysaccharides. In addition, sulfation at the 4-O
      position decreases markedly in the dermatan sulfate from adult sea urchin when
      compared with the glycan from larvae. Overall, these results demonstrate the
      occurrence of dermatan sulfates with unique sulfation patterns in this marine
      invertebrate. The physiological implication of these oversulfated dermatan
      sulfates is unclear. One hypothesis is that interactions between components of
      the extracellular matrix in marine invertebrates occur at higher salt
      concentrations than in vertebrates and therefore require glycosaminoglycans with
      increased charge density.

PMID- 11445549
TI  - Expression of M-N#1, a histo-blood group B-like antigen, is strongly up-regulated
      in nonapoptosing mammary epithelial cells during rat mammary gland involution.
AB  - Antibodies against the histo-blood group B-like antigen M-N#1 efficiently block
      the growth in vivo of rat mammary carcinoma cells that bear the antigen (Sleeman
      et al., 1999, Oncogene 18, 4485--4494). To try to understand the function of the
      M-N#1 antigen, we investigated when and where the antigen is expressed during the
      normal function of the rat mammary gland. Expression was virtually only seen
      during mammary gland involution. Here, strong expression of the antigen was
      observed in mammary epithelial cells, beginning around 2 days postweaning and
      lasting throughout the involution process. Dexamethasone treatment of animals
      postlactation inhibited alveolar collapse and remodeling in the mammary gland but
      inhibited neither the apoptosis of mammary epithelial cells nor the expression of
      the M-N#1 antigen. We show that up-regulation of carbohydrate antigens is not a
      general phenomenon during mammary gland involution, and thus that M-N#1 antigen
      expression is specifically regulated. Up-regulation of
      alpha(1,2)fucosyltransferase A, an enzyme required for M-N#1 antigen synthesis,
      is at least partly responsible for regulated M-N#1 antigen expression
      postlactation. Most significantly, we observed that the M-N#1 antigen is
      virtually exclusively expressed on nonapoptosing epithelial cells in the
      involuting mammary gland. These data suggest that M-N#1 antigen expression might
      either provide a survival function and/or be expressed in epithelial cells that
      are destined to grow and remodel mammary duct structures.

PMID- 11445550
TI  - Mouse anti-ceramide antiserum: a specific tool for the detection of endogenous
      ceramide.
AB  - Ceramide is a pivotal molecule in signal transduction and an essential structural
      component of the epidermal permeability barrier. The epidermis is marked by a
      high concentration of ceramide and by a unique spectrum of ceramide species:
      Besides the two ceramide structures commonly found in mammalian tissue, N
      acylsphingosine and N-2-hydroxyacyl-sphingosine, six additional ceramides
      differing in the grade of hydroxylation of either the sphingosine base or the
      fatty acid have been identified in the epidermis. Here we report on the
      characterization of an IgM-enriched polyclonal mouse serum against ceramide. In
      dot blot assays with purified epidermal lipids the antiserum bound to a similar
      extent to N-acyl-sphingosine (ceramide 2), N-acyl-4-hydroxysphinganine (ceramide
      3), and N-(2-hydroxyacyl)-sphingosine (ceramide 5), whereas no specific reaction
      was detected with glycosylceramides, sphingomyelin, free sphingosine,
      phospholipids, or cholesterol. In contrast, a monoclonal IgM antibody, also
      claimed to be specific for ceramide, was shown to bind specifically to
      sphingomyelin and therefore was not further investigated. In thin-layer
      chromatography immunostaining with purified lipids a strong and highly
      reproducible reaction of the antiserum with ceramide 2 and ceramide 5 was
      observed, whereas the reaction with ceramide 1 and ceramide 3 was weaker and more
      variable. Ceramide 2 and ceramide 5 were detected in the nanomolar range at serum
      dilutions of up to 1:100 by dot blot and thin-layer immunostaining. In thin-layer
      chromatography immunostaining of crude lipid extracts from human epidermis, the
      antiserum also reacted with N-(2-hydroxyacyl)-4-hydroxysphinganine (ceramide 6)
      and N-(2-hydroxyacyl)-6-hydroxysphingosine (ceramide 7). Furthermore, the
      suitability of the antiserum for the detection of endogenous ceramide by
      immunolight microscopy was demonstrated on cryoprocessed human skin tissue.
      Double immunofluorescence labeling experiments with the anti-ceramide antiserum
      and the recently described anti-glucosylceramide antiserum (Brade et al., 2000,
      Glycobiology 10, 629) showed that both lipids are concentrated in separate
      epidermal sites. Whereas anti-ceramide stained the dermal and basal epidermal
      cells as well as the corneocytes, anti-glucosylceramide staining was concentrated
      in the stratum granulosum. In conclusion, the specificity and sensitivity of the
      reagent will enable studies on the subcellular distribution and biological
      functions of endogenous ceramide.

PMID- 11445551
TI  - In vivo glycosylation of mucin tandem repeats.
AB  - The biochemical and biophysical properties of mucins are largely determined by
      extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR)
      domains. In a number of human diseases aberrant O-glycosylation is associated
      with variations in the properties of the cell surface-associated and secreted
      mucins. To evaluate in vivo the O-glycosylation of mucin TR domains, we generated
      recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B,
      which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F).
      These hybrid mucins were extensively O-glycosylated and showed the expected
      association with the cell surface and release into culture media. The presence of
      different TR domains within the chimeric mucins appears to have limited influence
      on their posttranslational processing. Alterations in glycosylation were detailed
      by fast atom bombardment mass spectrometry and reactivity with antibodies against
      particular blood-group and tumor-associated carbohydrate antigens. Future
      applications of these chimeras will include investigations of mucin
      posttranslational modification in the context of disease.

PMID- 11445552
TI  - Sulfatide promotes the folding of proinsulin, preserves insulin crystals, and
      mediates its monomerization.
AB  - Sulfatide is a glycolipid that has been associated with insulin-dependent
      diabetes mellitus. It is present in the islets of Langerhans and follows the same
      intracellular route as insulin. However, the role of sulfatide in the beta cell
      has been unclear. Here we present evidence suggesting that sulfatide promotes the
      folding of reduced proinsulin, indicating that sulfatide possesses molecular
      chaperone activity. Sulfatide associates with insulin by binding to the insulin
      domain A8--A10 and most likely by interacting with the hydrophobic side chains of
      the dimer-forming part of the insulin B-chain. Sulfatide has a dual effect on
      insulin. It substantially reduces deterioration of insulin hexamer crystals at pH
      5.5, conferring stability comparable to those in beta cell granules. Sulfatide
      also mediates the conversion of insulin hexamers to the biological active
      monomers at neutral pH, the pH at the beta-cell surface. Finally, we report that
      inhibition of sulfatide synthesis with chloroquine and fumonisine B1 leads to
      inhibition of insulin granule formation in vivo. Our observations suggest that
      sulfatide plays a key role in the folding of proinsulin, in the maintenance of
      insulin structure, and in the monomerization process.

PMID- 11445553
TI  - Comparison of the expression of cell surface poly-N-acetyllactosamine-type
      oligosaccharides in PC12 cells with those in its variant PC12D.
AB  - To explore the biological role of carbohydrate chains in the process of nerve
      cell differentiation, we carried out a characterization of the carbohydrate
      structure of glycoproteins by comparing conventional PC12 cells with variant
      cells (PC12D). In vitro metabolic labeling of cells with either [(3)H]
      glucosamine or [(3)H] threonine, together with tomato lectin staining, revealed
      that nerve growth factor (NGF) stimulation caused a decrease in the poly-N
      acetyllactosamine synthesis of high-molecular-weight glycopeptides from PC12
      cells. By comparison, the amount of glycopeptides with poly-N-acetyllactosamine
      from PC12D cells was already significantly low and it was not changed by NGF
      stimulation. By assaying the glycosyltransferases that participate in poly-N
      acetyllactosamine synthesis, the decrease in the amount of the poly-N
      acetyllactosamine in PC12D cells as well as NGF-stimulated PC12 cells could be
      accounted for by a reduction in the activity of poly-N-acetyllactosamine
      extension enzyme (GnT-i), because the amount of poly-N-acetyllactosamine in both
      cells precisely correlated with changes in GnT-i activity, whereas the activities
      of N-acetylglucosaminyltransferase V (GnT-V) and beta 1-4 galactosyltransferase
      remained unchanged. These results demonstrate that the decrease in poly-N
      acetyllactosamine synthesis in PC12 cells occurred prior to neurite formation,
      whereas PC12D cells were insensitive to this effect. Next, we showed that GnT-i
      but not GnT-V catalyzed a rate-limiting reaction in the expression of poly-N
      acetyllactosamine chains, especially in pheochromocytoma.

PMID- 11445554
TI  - Molecular cloning and expression of two distinct human N-acetylgalactosamine 4-O
      sulfotransferases that transfer sulfate to GalNAc beta 1-->4GlcNAc beta 1-->R in
      both N- and O-glycans.
AB  - Recently, cDNAs encoding human chondroitin 4-O-sulfotransferase-1 and -2 (C4ST-1
      and C4ST-2) were cloned based on their similarity to HNK-1 sulfotransferase (HNK
      1ST) (Hiraoka, N., Nakagawa, H., Ong, E., Akama, T.O., Fukuda, M.N., and Fukuda,
      M. [2000] Molecular cloning and expression of two distinct human chondroitin 4-O
      sulfotransferases that belong to the HNK-1 sulfotransferase gene family. J. Biol.
      Chem., 275, 20188--20196). In the present study, we identified two additional
      novel sulfotransferases by searching the expression sequence tag and genomic DNA
      database for enzymes similar to C4ST-1 and C4ST-2. These newly cloned enzymes,
      termed GalNAc4ST-1 and GalNAc4ST-2, belong to the HNK-1ST gene family having 40-
      42% identity with C4ST-1. GalNAc4ST-1 and -2 do not add sulfate to HNK-1
      precursor glycans, chondroitin, or desulfated dermatan sulfate. Instead, both
      enzymes can transfer sulfate to the 4-position of GalNAc in the context of GalNAc
      beta 1-->4GlcNAc beta 1-->R attached to both N-linked and core 2 branched O
      linked oligosaccharides. GalNAc4ST-1 and -2 transcripts are highly expressed in
      the pituitary gland and trachea, respectively, and GalNAc4ST-1 and -2 transcripts
      are reciprocally expressed in other tissues as well. Moreover, both enzymes can
      transfer sulfate to lutropin, a pituitary glycoprotein hormone. These combined
      results indicate that GalNAc4ST-1 and -2 play critical roles in forming sulfo-
      >4GalNAc beta 1-->4GlcNAc beta 1-->R in both N-glycans and O-glycans in a tissue
      specific manner.

PMID- 11445555
TI  - Analysis of heparan sulfate oligosaccharides by nano-electrospray ionization mass
      spectrometry.
AB  - A highly sensitive method to identify and quantify heparan sulfate (HS)
      oligosaccharides by using nano-electrospray ionization mass spectrometry (nESI
      MS) is described. The new approach allows us to detect approximately 50 nM of a
      chemically synthesized pentasaccharide with a structure of GlcNS6S-GlcA-GlcNS6S
      IdoA2S-GlcNS6SOMe (3-OH pentasaccharide). Typically, solutions were infused for a
      total of 5 min, at an average flow rate of 30 nl/min, and the remaining sample
      was recovered from the nanovial. The spectra shown were obtained by summing scans
      for 1--3 min. Hence, our data indicated that as little as 3 x 10(-15) mole of the
      pentasaccharide was consumed to obtain a reasonable spectrum at the concentration
      as low as 50 nM. In addition, we found a linear relationship between the relative
      response of the molecular ion and the concentration of the analyzed 3-OH
      pentasaccharide, demonstrating that this approach can be used to determine the
      amount of HS oligosaccharides. To this end, a 3-O-sulfated pentasaccharide was
      prepared by incubating the 3-OH pentasaccharide with purified HS 3-O
      sulfotransferase-1 and 3'-phosphoadenosine-5'-phospho[(35)S]sulfate. The
      resulting 3-O-sulfated pentasaccharide was purified and analyzed by nESI-MS.
      Based on the standard curve constructed with the 3-OH pentasaccharide, we
      calculated the concentration of the 3-O-sulfated pentasaccharide by the relative
      response. The result indicates that this value is very close to the value
      measured by [(35)S]sulfate radioactivity. In conclusion, nESI-MS provides both
      high sensitivity and the capacity to quantify HSs. This approach is likely to
      become a very important tool for structural analysis and sequencing of HS and
      heparin oligosaccharides.

PMID- 11445556
TI  - LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest.
AB  - Inactivating mutations in the serine-threonine kinase LKB1 (STK11) are found in
      most patients with Peutz-Jeghers syndrome; however the function of LKB1 is
      unknown. We found that LKB1 binds to and regulates brahma-related gene 1 (Brg1),
      an essential component of chromatin remodeling complexes. The association
      requires the N terminus of LKB1 and the helicase domain of Brg1 and LKB1
      stimulates the ATPase activity of Brg1. Brg1 expression in SW13 cells induces the
      formation of flat cells indicative of cell cycle arrest and senescence.
      Expression of a kinase-dead mutant of LKB1, SL26, in SW13 cells blocks the
      formation of Brg1-induced flat cells, indicating that LKB1 is required for Brg1
      dependent growth arrest. The inability of mutants of LKB1 to mediate Brg1
      dependent growth arrest may explain the manifestations of Peutz-Jeghers syndrome.

PMID- 11445557
TI  - Regulation of Akt/PKB activation by tyrosine phosphorylation.
AB  - Activation of Akt/PKB by growth factors requires multiple phosphorylation events.
      Phosphorylation of Thr(308) and Ser(473) of Akt by its upstream kinase(s) or
      autophosphorylation is critical for optimal activation of its kinase activity.
      Here, we present evidence that tyrosine phosphorylation is required for Akt
      activation. Epidermal growth factor treatment induces tyrosine phosphorylation of
      Akt in COS1 and PC3M cells, which is abrogated by PP2, a selective inhibitor for
      Src family tyrosine kinases. Elevated Akt activity is observed in v-Src
      transformed NIH3T3 cells, which is accompanied with increased tyrosine
      phosphorylation of Akt. Akt activity induced by growth factors is significantly
      reduced in SYF cells lacking Src, Yes, and Fyn, which can be restored by
      introducing c-Src, but not the kinase-inactive Src, back to these cells.
      Furthermore, we have identified two tyrosine residues near the activation loop of
      Akt that are important for its activation. Substitution of these residues with
      phenylalanine abolishes Akt kinase activity stimulated by growth factors. These
      two YF mutants fail to block Forkhead transcription factor activity in 293 cells
      and are unable to prevent apoptosis induced by matrix detachment. Our data
      suggest that, in addition to phosphorylation of Thr(308) and Ser(473), tyrosine
      phosphorylation of Akt may be essential for its biological function.

PMID- 11445558
TI  - Identification of a nonpeptide ligand that releases bioactive insulin-like growth
      factor-I from its binding protein complex.
AB  - Insulin-like growth factor-I (IGF-I) has both metabolic and mitogenic activities
      mediated through interaction with the type 1 IGF receptor. The circulation of IGF
      I in blood and interstitial fluid is not free but bound mostly to a family of six
      high affinity IGF-binding proteins, which form stable complexes with IGF and
      neutralize its bioactivity. Therefore, displacement of this large pool of
      endogenous IGF from the binding proteins could elevate "free" IGF levels to
      elicit beneficial effects in diabetes and other IGF-responsive diseases
      comparable with those produced by administration of exogenous IGF-I. We report
      here the identification of a nonpeptide ligand NBI-31772, which displaces IGF-I
      from all six IGF-binding proteins at low nanomolar concentrations from screening
      of the in-house chemical libraries. Furthermore, the released free IGF-I was
      shown to be biologically active in an in vitro bioassay. Thus, NBI-31772 could
      serve as a valuable lead molecule for the design of novel therapeutics to treat
      diabetes and other IGF-responsive diseases.

PMID- 11445559
TI  - Linking global histone acetylation to the transcription enhancement of X
      chromosomal genes in Drosophila males.
AB  - It has become well established for several genes that targeting of histone
      acetylation to promoters is required for the activation of transcription. In
      contrast, global patterns of acetylation have not been ascribed to any particular
      regulatory function. In Drosophila, a specific modification of H4, acetylation at
      lysine 16, is enriched at hundreds of sites on the male X chromosome due to the
      activity of the male-specific lethal (MSL) dosage compensation complex. Utilizing
      chromatin immunoprecipitation, we have determined that H4Ac16 is present along
      the entire length of X-linked genes targeted by the MSL complex with relatively
      modest levels of acetylation at the promoter regions and high levels in the
      middle and/or 3' end of the transcription units. We propose that global
      acetylation by the MSL complex increases the expression of X-linked genes by
      facilitating transcription elongation rather than by enhancing promoter
      accessibility. We have also determined that H4Ac16 is absent from a region of the
      X chromosome that includes a gene known to be dosage-compensated by a MSL
      independent mechanism. This study represents the first biochemical interpretation
      of the very large body of cytological observations on the chromosomal
      distribution of the MSL complex.

PMID- 11445560
TI  - Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice
      lacking both leptin and the low density lipoprotein receptor.
AB  - Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin
      resistance, and diabetes, all of which are components of a multiple risk factor
      syndrome that, along with hypercholesterolemia, precipitates a potential high
      risk for atherosclerosis. In the current study, we show an unexpectedly severe
      hyperlipidemia in ob/ob mice on a background of low density lipoprotein receptor
      (LDLR) deficiency (-/-). Doubly mutant mice (LDLR-/-;ob/ob) exhibited striking
      elevations in both total plasma cholesterol (TC) and triglyceride (TG) levels
      (1715 +/- 87 and 1016 +/- 172 mg/dl, respectively), at age 3-4 months, resulting
      in extensive atherosclerotic lesions throughout the aorta by 6 months.
      Lipoprotein analyses revealed the elevated TC and TG levels to be due to a large
      increase in an apoB-containing broad-beta remnant lipoprotein fraction. While
      fasting, diet restriction, and low level leptin treatment significantly lowered
      TG levels, they caused only slight changes in TC levels. Hepatic cholesterol and
      triglyceride contents as well as mRNA levels of cholesterologenic and lipogenic
      enzymes suggest that leptin deficiency increased hepatic triglyceride production
      but did not change cholesterol production in ob/ob mice regardless of their LDLR
      genotype. These data provide evidence that the hypertriglyceridemia and
      hypercholesterolemia in the doubly mutant mice are caused by distinct mechanisms
      and point to the possibility that leptin might have some impact on plasma
      cholesterol metabolism, possibly through an LDLR-independent pathway. This model
      will be an excellent tool for future studies on the relationship between impaired
      fuel metabolism, increased plasma remnant lipoproteins, diabetes, and
      atherosclerosis.

PMID- 11445561
TI  - Gene- and activation-specific mechanisms for insulin inhibition of basal and
      glucocorticoid-induced insulin-like growth factor binding protein-1 and
      phosphoenolpyruvate carboxykinase transcription. Roles of forkhead and insulin
      response sequences.
AB  - The insulin response sequence (IRS) of the phosphoenolpyruvate carboxykinase
      (PEPCK) promoter, located within the glucocorticoid response unit, was first
      characterized by its ability to mediate insulin inhibition when inserted into a
      thymidine kinase promoter. The IRSs of the PEPCK and insulin-like growth factor
      binding protein-1 (IGFBP-1) promoters have been proposed to contribute to
      regulation by glucocorticoids and insulin. Forkhead (FKHR) recognizes IRS
      sequences, is phosphorylated in response to insulin, and mediates insulin
      inhibition of basal IGFBP-1 transcription in an IRS-dependent manner. Here, we
      investigate the contributions of FKHR and IRSs to insulin inhibition of basal and
      glucocorticoid-induced transcription of PEPCK and IGFBP-1. Expression of T/S/S,
      in which three putative protein kinase B (PKB) sites in FKHR are mutated, reduced
      insulin inhibition of basal expression of IGFBP-1 but not PEPCK. Mutation of the
      IGFBP-1 IRSs abolished insulin inhibition in the presence of T/S/S. Mutation of
      the PEPCK IRS had no effect on insulin inhibition in the presence of T/S/S,
      indicating that insulin inhibits PEPCK transcription independently of the IRS or
      of the putative PKB phosphorylation sites in FKHR. Mutations in the IRS or FKHR
      had no effect on insulin inhibition of glucocorticoid-induced transcription of
      either the PEPCK or IGFBP-1 gene. Thus, insulin uses gene- and activation
      specific mechanisms to regulate the basal and glucocorticoid-induced activity of
      these genes.

PMID- 11445562
TI  - Genetic interactions with the yeast Q-SNARE VTI1 reveal novel functions for the R
      SNARE YKT6.
AB  - SNARE proteins are required for fusion of transport vesicles with target
      membranes. Previously, we found that the yeast Q-SNARE Vti1p is involved in
      transport to the cis-Golgi, to the prevacuole/late endosome, and to the vacuole.
      Here we identified a previously uncharacterized gene, VTS1, and the R-SNARE YKT6
      both as multicopy and as low copy suppressors of the growth and vacuolar
      transport defect in vti1-2 cells. Ykt6p was known to function in retrograde
      traffic to the cis-Golgi and homotypic vacuolar fusion. We found that VTI1 and
      YKT6 also interacted in traffic to the prevacuole and vacuole, indicating that
      these SNARE complexes contain Ykt6p, Vti1p, plus Pep12p and Ykt6p, Vti1p, Vam3p,
      plus Vam7p, respectively. As Ykt6p was required for several transport steps, R
      SNAREs cannot be the sole determinants of specificity. To study the role of the 0
      layer in the SNARE motif, we introduced the mutations vti1-Q158R and ykt6-R165Q.
      SNARE complexes to which Ykt6p contributed a fourth glutamine residue in the 0
      layer were nonfunctional, suggesting an essential function for arginine in the 0
      layer of these complexes. vti1-Q158R cells had severe defects in several
      transport steps, indicating that the second arginine in the 0 layer interfered
      with function.

PMID- 11445563
TI  - Novel intra- and inter-molecular sulfinamide bonds in S100A8 produced by
      hypochlorite oxidation.
AB  - Hypochlorite is a major oxidant generated when neutrophils and macrophages are
      activated at inflammatory sites, such as in atherosclerotic lesions. Murine
      S100A8 (A8) is a major cytoplasmic protein in neutrophils and is secreted by
      macrophages in response to inflammatory stimuli. After incubation with reagent
      HOCl for 10 min, approximately 85% of A8 was converted to 4 oxidation products,
      with electrospay ionization mass spectrometry masses of m/z 10354, 10388, 10354
      +/- 1, and 20707 +/- 3. All were resistant to reduction by dithiothreitol.
      Initial formation of a reactive Cys sulfenic acid intermediate was demonstrated
      by the rapid conjugation of 5,5-dimethyl-1,3-cyclohexanedione (dimedone) to HOCl
      treated A8 to form stable adducts. Matrix-assisted laser desorption-reflectron
      time of flight peptide mass fingerprinting of isolated oxidation products
      confirmed the mass additions observed in the full-length proteins. Both
      Met(36/73) were converted to Met(36/73) sulfoxides. An additional product with an
      unusual mass addition of m/z 14 (+/-0.2) was identified and corresponded to the
      addition of oxygen to Cys(41), conjugation to various epsilon-amines of Lys(6),
      Lys(34/35), or Lys(87) with loss of dihydrogen and formation of stable intra- or
      inter-molecular sulfinamide cross-links. Specific fragmentations identified in
      matrix-assisted laser desorption-post source decay spectra and low energy
      collisional-induced dissociation tandem mass spectroscopy spectra of sulfinamide
      containing digest peptides confirmed Lys(34/35) to Cys(41) sulfinamide bonds.
      HOCl oxidation of mutants lacking Cys(41) (Ala(41)S100A8) or specific Lys
      residues (e.g. Lys(34/35), Ala(34/35)S100A8) did not form sulfinamide cross
      links. HOCl generated by myeloperoxidase and H(2)O(2) and by phorbol 12-myristate
      13-acetate-activated neutrophils also formed these products(.) In contrast to the
      disulfide-linked dimer, oxidized monomer retained normal chemotactic activity for
      neutrophils. Sulfinamide bond formation represents a novel oxidative cross
      linking process between thiols and amines and may be a general consequence of
      HOCl protein oxidation in inflammation not identified previously. Similar
      modifications in other proteins could potentially regulate normal and
      pathological processes during aging, atherogenesis, fibrosis, and neurogenerative
      diseases.

PMID- 11445564
TI  - Association of chondroadherin with collagen type II.
AB  - Chondroadherin is a cell binding, leucine-rich repeat protein found in the
      territorial matrix of articular cartilage. Several members of the leucine-rich
      repeat protein family present in the extracellular matrix of e.g. cartilage have
      been shown to interact with collagen and influence collagen fibrillogenesis. We
      show that complexes of monomeric collagen type II and chondroadherin can be
      released under non-denaturing conditions from articular cartilage treated with p
      aminophenylmercuric acetate to activate resident matrix metalloproteinases.
      Purified complexes as well as complexes formed in vitro between recombinant
      chondroadherin and collagen type II were studied by electron microscopy.
      Chondroadherin was shown to bind to two sites on collagen type II. The
      interaction was characterized by surface plasmon resonance analysis showing K(D)
      values in the nanomolar range. Both chondroadherin and collagen interact with
      chondrocytes, partly via the same receptor, but give rise to different cellular
      responses. By also interacting with each other, a complex system is created which
      may be of functional importance for the communication between the cells and its
      surrounding matrix and/or in the regulation of collagen fibril assembly.

PMID- 11445565
TI  - Molecular cloning and characterization of human nonsteroidal anti-inflammatory
      drug-activated gene promoter. Basal transcription is mediated by Sp1 and Sp3.
AB  - Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is known to be
      associated with anti-tumorigenic activity and belongs to the transforming growth
      factor-beta superfamily. In the present study, we cloned the promoter region (
      3500 to +41) and investigated the transcriptional regulatory mechanisms of the
      basal expression of the human NAG-1 gene. Several potential transcription factor
      binding sites in this region were identified. Based on the results from clones of
      nested deletions, the construct between -133 and +41 base pairs contains three
      Sp1-binding sites (Sp1-A, Sp1-B, and Sp1-C), which confer basal transcription
      specific activity of NAG-1 expression. When the Sp1-C site was mutated (GG to
      TT), a 60-80% decrease in promoter activity was observed in HCT-116 cells. Gel
      shift, co-transfection, and chromatin immunoprecipitation assays showed that the
      Sp transcription factors bind to the Sp1-binding sites and transactivate NAG-1
      expression. In addition, chicken ovalbumin upstream promoter-transcription factor
      1 can interact with the C-terminal region of Sp1 and Sp3 proteins and induce NAG
      1 promoter activity through Sp1 and Sp3 transcription factors. These results
      identify the critical regulatory regions for the human NAG-1 basal promoter.
      Furthermore, the results suggest that the level of expression of the NAG-1 gene
      will depend on the availability of Sp proteins and on co-factors such as chicken
      ovalbumin upstream promoter-transcription factor 1.

PMID- 11445566
TI  - Glucose-induced oscillations in cytoplasmic free Ca2+ concentration precede
      oscillations in mitochondrial membrane potential in the pancreatic beta-cell.
AB  - Using dual excitation and fixed emission fluorescence microscopy, we were able to
      measure changes in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and
      mitochondrial membrane potential simultaneously in the pancreatic beta-cell. The
      beta-cells were exposed to a combination of the Ca(2+) indicator fura-2/AM and
      the indicator of mitochondrial membrane potential, rhodamine 123 (Rh123). Using
      simultaneous measurements of mitochondrial membrane potential and [Ca(2+)](i)
      during glucose stimulation, it was possible to measure the time lag between the
      onset of mitochondrial hyperpolarization and changes in [Ca(2+)](i). Glucose
      induced oscillations in [Ca(2+)](i) were followed by transient depolarizations of
      mitochondrial membrane potential. These results are compatible with a model in
      which nadirs in [Ca(2+)](i) oscillations are generated by a transient, Ca(2+)
      induced inhibition of mitochondrial metabolism resulting in a temporary fall in
      the cytoplasmic ATP/ADP ratio, opening of plasma membrane K(ATP) channels,
      repolarization of the plasma membrane, and thus transient closure of voltage
      gated L-type Ca(2+) channels.

PMID- 11445567
TI  - Cooperative regulation of the invasive and metastatic phenotypes by different
      domains of the type I insulin-like growth factor receptor beta subunit.
AB  - The receptor for the type 1 insulin-like growth factor (IGF-I) regulates multiple
      cellular functions impacting on the metastatic phenotype of tumor cells,
      including cellular proliferation, anchorage-independent growth, survival,
      migration, synthesis of the 72-kDa type IV collagenase and invasion. We have used
      site-directed mutagenesis to generate domain-specific mutants of the receptor
      beta subunit to analyze the role of specific tyrosines in the regulation of the
      invasive/metastatic phenotype. Poorly invasive M-27 carcinoma cells expressing
      low receptor numbers were transfected with a plasmid vector expressing IGF-I
      receptor cDNA in which single or multiple tyrosine codons in the kinase domain,
      namely Tyr-1131, Tyr-1135, and Tyr-1136 or the C-terminal tyrosines 1250 and 1251
      were substituted with phenylalanine. Changes in the invasive and metastatic
      properties were analyzed relative to M-27 cells expressing the wild type
      receptor. We found that cells expressing the Y1131F,Y1135F,Y1136F or Y1135F
      receptor mutants lost all IGF-IR-dependent functions and their phenotypes were
      indistinguishable from, or suppressed relative to, the parent line. The
      Y1250F,Y1251F substitution abolished anchorage-independent growth, cell
      spreading, and the anti-apoptotic effect of IGF-I whereas all other IGF-IR
      dependent phenotypes were either unperturbed (i.e. mitogenicity) or only
      partially reduced (migration and invasion). The results identify three types of
      receptor-dependent functions in this model: those dependent only on an intact
      kinase domain (DNA synthesis), those dependent equally on kinase domain and Tyr
      1250/1251 signaling (e.g. apoptosis, soft agar cloning) and those dependent on
      kinase domain and enhanced through Tyr-1250/1251 signaling (migration, invasion).
      They suggest that signals derived from both regions of the receptor cooperate to
      enhance tumor metastasis.

PMID- 11445568
TI  - Analysis of the minimal amyloid-forming fragment of the islet amyloid
      polypeptide. An experimental support for the key role of the phenylalanine
      residue in amyloid formation.
AB  - The development of type II diabetes was shown to be associated with the formation
      of amyloid fibrils consisted of the islet amyloid polypeptide (IAPP or amylin).
      Recently, a short functional hexapeptide fragment of IAPP (NH(2)-NFGAIL-COOH) was
      found to form fibrils that are very similar to those formed by the full-length
      polypeptide. To better understand the specific role of the residues that compose
      the fragment, we performed a systematic alanine scan of the IAPP "basic
      amyloidogenic units." Turbidity assay experiments demonstrated that the wild-type
      peptide and the Asn(1) --> Ala and Gly(3) --> Ala peptides had the highest rate
      of aggregate formation, whereas the Phe(2) --> Ala peptide did not form any
      detectable aggregates. Dynamic light-scattering experiments demonstrated that all
      peptides except the Phe(2) --> Ala form large multimeric structures. Electron
      microscopy and Congo red staining confirmed that the structures formed by the
      various peptides are indeed amyloid fibrils. Taken together, the results of our
      study provide clear experimental evidence for the key role of phenylalanine
      residue in amyloid formation by IAPP. In contrast, glycine, a residue that was
      suggested to facilitate amyloid formation in other systems, has only a minor
      role, if any, in this case. Our results are discussed in the context of the
      remarkable occurrence of aromatic residues in short functional fragments and
      potent inhibitors of amyloid-related polypeptides. We hypothesize that pi-pi
      interactions may play a significant role in the molecular recognition and self
      assembly processes that lead to amyloid formation.

PMID- 11445569
TI  - The catalog of human hair keratins. II. Expression of the six type II members in
      the hair follicle and the combined catalog of human type I and II keratins.
AB  - The human type II hair keratin subfamily consists of six individual members and
      can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are
      structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather
      distinct. Specific antisera against the individual hair keratins were used to
      establish the two-dimensional catalog of human type II hair keratins. In this
      catalog, hHb5 showed up as a series of isoelectric variants, well separated from
      a lower, more acidic, and complex protein streak containing isoelectric variants
      of hair keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and
      immunohistochemistry on anagen hair follicles showed that hHb5 and hHb2 defined
      early stages of hair differentiation in the matrix (hHb5) and cuticle (hHb5 and
      hHb2), respectively. Although cuticular differentiation proceeded without the
      expression of further type II hair keratins, cortex cells simultaneously
      expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In
      contrast, hHb4, which is undetectable in hair follicle extracts and sections,
      could be identified as the largest and most alkaline member of this subfamily in
      cytoskeletal extracts of dorsal tongue. This hair keratin was localized in the
      posterior compartment of the tongue filiform papillae. Comparative analysis of
      type II with the previously published type I hair keratin expression profiles
      suggested specific, but more likely, random keratin-pairing principles during
      trichocyte differentiation. Finally, by combining the previously published type I
      hair keratin catalog with the type II hair keratin catalog and integrating both
      into the existing catalog of human epithelial keratins, we present a two
      dimensional compilation of the presently known human keratins.

PMID- 11445570
TI  - Effects of macromolecular crowding on the refolding of glucose- 6-phosphate
      dehydrogenase and protein disulfide isomerase.
AB  - The effects of polysaccharide, polyethylene glycol, and protein-crowding agents
      on the refolding of glucose-6-phosphate dehydrogenase (G6PDH) and protein
      disulfide isomerase have been examined. By increasing concentration during
      refolding, the reactivation yields of the two proteins decrease with the
      formation of soluble aggregates. In the presence of high concentrations of
      crowding agents the reactivation yields remain constant but with decreased
      refolding rates. The refolding of G6PDH changes from monophasic to biphasic first
      order reactions in the presence of crowding agents, and the amplitude of the new
      slow phase increases with increasing concentrations of crowding agents. The
      molecular chaperone GroEL reverses the refolding kinetics of G6PDH from biphase
      back to monophase and accelerates the refolding process. Our results display the
      complexity and diversity of the effects of macromolecular crowding on both the
      thermodynamics and kinetics of protein folding.

PMID- 11445571
TI  - Mapping the sites of interaction between SecY and SecE by cysteine scanning
      mutagenesis.
AB  - In Escherichia coli, the SecYEG complex mediates the translocation and membrane
      integration of proteins. Both genetic and biochemical data indicate interactions
      of several transmembrane segments (TMSs) of SecY with SecE. By means of cysteine
      scanning mutagenesis, we have identified intermolecular sites of contact between
      TMS7 of SecY and TMS3 of SecE. The cross-linking of SecY to SecE demonstrates
      that these subunits are present in a one-to-one stoichiometry within the SecYEG
      complex. Sites in TMS3 of SecE involved in SecE dimerization are confined to a
      specific alpha-helical interface and occur in an oligomeric SecYEG complex.
      Although cross-linking reversibly inactivates translocation, the contact between
      TMS7 of SecY and TMS3 of SecE remains unaltered upon insertion of the preprotein
      into the translocation channel. These data support a model for an oligomeric
      translocation channel in which pairs of SecYEG complexes contact each other via
      SecE.

PMID- 11445572
TI  - Unravelling the interaction of thapsigargin with the conformational states of
      Ca(2+)-ATPase from skeletal sarcoplasmic reticulum.
AB  - Preincubation of thapsigargin with sarcoplasmic reticulum vesicles in the
      presence of high Ca(2+) or the addition of high Ca(2+) to microsomal vesicles
      preincubated with thapsigargin in the absence of Ca(2+) allowed full enzyme
      phosphorylation by ATP. However, the enzyme activity was not protected by high
      Ca(2+) even when the samples were subjected to gel filtration before ATP
      addition. Our data indicate that: (i) the enzyme in the Ca(2+)-bound conformation
      can be stabilized in the presence of thapsigargin; (ii) the conformational
      transition from the Ca(2+)-free to the Ca(2+)-bound state can be elicited by
      Ca(2+) when thapsigargin is present; (iii) thapsigargin binding occurs whether or
      not the enzyme is in the presence of Ca(2+), and so a ternary complex enzyme
      Ca(2+)-thapsigargin may be formed; (iv) thapsigargin can be dissociated from the
      enzyme with a slow kinetics after dilution under drastic conditions; (v) the
      kinetics of Ca(2+) binding is clearly slowed down by thapsigargin; and (vi)
      thapsigargin does not affect the hydrolysis rate of phosphorylating substrates
      when measured in the absence of Ca(2+), indicating that thapsigargin specifically
      inhibits the Ca(2+)-dependent activity.

PMID- 11445573
TI  - Crystal structure of a complex between Pseudomonas aeruginosa alkaline protease
      and its cognate inhibitor: inhibition by a zinc-NH2 coordinative bond.
AB  - Serralysins are a family of metalloproteases secreted by Gram-negative bacteria
      into the medium in the form of inactive zymogens. Usually, all serralysin
      secretors have on the same operon a gene coding for a periplasmic 10-kDa protein,
      which is an inhibitor of the secreted protease. The recent characterization of
      the inhibitor of the alkaline protease from Pseudomonas aeruginosa revealed a
      surprisingly low dissociation constant of 4 pm, contrary to earlier studies on
      homologous systems, where inhibition constants in the microm range were reported.
      To approach a more accurate understanding, the crystal structure of the complex
      between inhibitor and protease from P. aeruginosa was determined at 1.74 A
      resolution and refined to R(free) = 0.204. The structure reported here shows
      clearly that the N terminus of the inhibitor forms a coordinative bond to the
      catalytic Zn(2+) ion with a nitrogen-zinc distance of 2.17 A. We conclude that
      this interaction adds substantially to the complex stability and show also that
      similar interactions are found in other metzincin-inhibitor complexes.

PMID- 11445574
TI  - Comparative biochemical and immunocytochemical studies reveal differences in the
      effects of Clostridium perfringens enterotoxin on polarized CaCo-2 cells versus
      Vero cells.
AB  - Since most in vitro studies exploring the action of Clostridium perfringens
      enterotoxin (CPE) utilize either Vero or CaCo-2 cells, the current study directly
      compared the CPE responsiveness of those two cell lines. When CPE-treated in
      suspension, both CaCo-2 and Vero cells formed SDS-resistant, CPE-containing
      complexes of approximately 135, approximately 155, and approximately 200 kDa.
      However, confluent Transwell cultures of either cell line CPE-treated for 20 min
      formed only the approximately 155-kDa complex. Since those Transwell cultures
      also exhibited significant (86)Rb release, approximately 155-kDa complex
      formation is sufficient for CPE-induced cytotoxicity. Several differences in CPE
      responsiveness between the two cell lines were also detected. (i) CaCo-2 cells
      were more sensitive when CPE-treated on their basal surface, whereas Vero cells
      were more sensitive when CPE-treated on their apical surface; those sensitivity
      differences correlated with CPE binding the apical versus basolateral surfaces of
      these two cell lines. (ii) CPE-treated Vero cells released (86)Rb into both
      Transwell chambers, whereas CaCo-2 cells released (86)Rb only into the CPE
      containing Transwell chamber. (iii) Vero cells express the tight junction (TJ)
      protein occludin but (unlike CaCo-2 cells) cannot form TJs. The ability of TJs to
      affect CPE responsiveness is supported by the similar effects of CPE on Transwell
      cultures of CaCo-2 cells and Madin-Darby canine kidney cells, another polarized
      cell forming TJs. Confluent CaCo-2 Transwell cultures CPE-treated for >1 h formed
      the approximately 200-kDa CPE complex (which also contains occludin), exhibited
      morphologic damage, and had occludin removed from their TJs. Collectively, these
      results identify CPE as a bifunctional toxin that, in confluent polarized cells,
      first exerts a cytotoxic effect mediated by the approximately 155-kDa complex.
      Resultant damage then provides CPE access to TJs, leading to approximately 200
      kDa complex formation, internalization of some TJ proteins, and TJ damage that
      may increase paracellular permeability and thereby contribute to the diarrhea of
      CPE-induced gastrointestinal disease.

PMID- 11445575
TI  - Functional analysis of Csk and CHK kinases in breast cancer cells.
AB  - In this report, we analyzed the expression and kinase activities of Csk and CHK
      kinases in normal breast tissues and breast tumors and their involvement in HRG
      mediated signaling in breast cancer cells. Csk expression and kinase activity
      were abundant in normal human breast tissues, breast carcinomas, and breast
      cancer cell lines, whereas CHK expression was negative in normal breast tissues
      and low in some breast tumors and in the MCF-7 breast cancer cell line. CHK
      kinase activity was not detected in human breast carcinoma tissues (12 of 12) or
      in the MCF-7 breast cancer cell line (due to the low level of CHK protein
      expression), but was significantly induced upon heregulin (HRG) stimulation. We
      have previously shown that CHK associates with the ErbB-2/neu receptor upon HRG
      stimulation via its SH2 domain and that it down-regulates the ErbB-2/neu
      activated Src kinases. Our new findings demonstrate that Csk has no effect on
      ErbB-2/neu-activated Src kinases upon HRG treatment and that its kinase activity
      is not modulated by HRG. CHK significantly inhibited in vitro cell growth,
      transformation, and invasion induced upon HRG stimulation. In addition, tumor
      growth of wt CHK-transfected MCF-7 cells was significantly inhibited in nude
      mice. Furthermore, CHK down-regulated c-Src and Lyn protein expression and kinase
      activity, and the entry into mitosis was delayed in the wt CHK-transfected MCF-7
      cells upon HRG treatment. These results indicate that CHK, but not Csk, is
      involved in HRG-mediated signaling pathways, down-regulates ErbB-2/neu-activated
      Src kinases, and inhibits invasion and transformation of breast cancer cells upon
      HRG stimulation. These findings strongly suggest that CHK is a novel negative
      growth regulator of HRG-mediated ErbB-2/neu and Src family kinase signaling
      pathways in breast cancer cells.

PMID- 11445576
TI  - Distinct transcriptional profiles of adipogenesis in vivo and in vitro.
AB  - Obesity, defined as an increase in adipose tissue mass, is the most prevalent
      nutritional disorder in industrialized countries and is a growing problem in
      developing countries. An increase in adipose tissue mass can be the result of the
      production of new fat cells through the process of adipogenesis and/or the
      deposition of increased amounts of cytoplasmic triglyceride per cell. Although
      much has been learned about the differentiation of adipocytes in vitro, less is
      known about the molecular basis for the mechanisms regulating adipogenesis in
      vivo. Here oligonucleotide microarrays have been used to compare the patterns of
      gene expression in preadipocytes and adipocytes in vitro and in vivo. These data
      indicate that the cellular programs associated with adipocyte differentiation are
      considerably more complex than previously appreciated and that a greater number
      of heretofore uncharacterized gene regulatory events are activated during this
      process in vitro. In addition, the gene expression changes associated with
      adipocyte development in vivo and in vitro, while overlapping, are in some
      respects quite different. These data further suggest that one or more
      transcriptional programs are activated exclusively in vivo to generate the full
      adipocyte phenotype. This gene expression survey now sets the stage for further
      studies to dissect the molecular differences between in vivo and in vitro
      adipocytes.

PMID- 11445577
TI  - Amino acid transporter CAATCH1 is also an amino acid-gated cation channel.
AB  - CAATCH1 (cation-amino acid transporter/channel) is a recently cloned insect
      epithelial membrane protein related to mammalian Na(+)-, Cl(-)-coupled
      neurotransmitter transporters (Feldman, D. H., Harvey, W. R., and Stevens, B. R.
      (2000) J. Biol. Chem. 275, 24518-24526). In the present study we analyze the
      relationship between CAATCH1-mediated amino acid transport and ion fluxes by
      utilizing the Xenopus oocyte expression system in conjunction with
      electrophysiology and radiotracer uptake. Simultaneous flux measurements reveal
      that electrical currents and amino acid transport are thermodynamically
      uncoupled. This observation is supported by measuring significant uptake even in
      the absence of external alkali cations. Remarkably, CAATCH1-associated Na(+) or
      K(+) currents are large and do not saturate with voltage nor with cation
      concentration. These currents reverse in Nernstian fashion, thereby conferring
      channel activity in CAATCH1. Upon step-changes in the membrane potential, CAATCH1
      expressing oocytes exhibit transient currents. Detailed analyses of these
      transients in the absence and presence of amino acids reveal direct ligand
      protein interaction, demonstrating that binding by different amino acids (e.g.
      proline, threonine, methionine) differentially affects the state probability of
      CAATCH1 but has no effect on the maximal charge movement (Q(max)). Together these
      data suggest that CAATCH1 is a multifunction membrane protein that mediates
      thermodynamically uncoupled amino acid uptake but functions predominantly as an
      amino acid-gated alkali cation channel.

PMID- 11445578
TI  - ERK regulates the hepatocyte growth factor-mediated interaction of Gab1 and the
      phosphatidylinositol 3-kinase.
AB  - Based on our previous observations that active ERK associates with and
      phosphorylates Gab1 in response to HGF, and the prediction that the ERK
      phosphorylation site is adjacent to one of the phosphatidylinositol 3-kinase
      (PI3K) SH2 binding motifs, we examined the possibility that ERK phosphorylation
      can regulate the Gab1/PI3K association. The HGF-mediated association of Gab1 with
      either full-length GST-p85 or its isolated N- or C-terminal SH2 domains was
      inhibited by approximately 50% in the setting of ERK inhibition, a result
      confirmed by co-immunoprecipitation of the native proteins. A 14-amino acid
      peptide encoding (472)YVPMTP(477) (one of the major p85 binding sites in Gab1 and
      the predicted ERK phosphorylation site) was synthesized with either
      phosphotyrosine alone (pY), or phosphotyrosine + phosphothreonine (pYT). In both
      pull-down assays and competition assays, pYT demonstrated a higher affinity for
      p85 than did pY alone. Finally, examination of the phosphorylation state of Akt
      after HGF stimulation revealed that ERK inhibition resulted in a decrease in Akt
      activation at both 5 and 10 min. These results suggest that activated ERK can
      phosphorylate Gab1 in response to HGF stimulation and thereby potentiate the
      Gab1/PI3K association and subsequent PI3K activation.

PMID- 11445579
TI  - A PDZ domain protein interacts with the C-terminal tail of the insulin-like
      growth factor-1 receptor but not with the insulin receptor.
AB  - In this study, we report on the isolation of a PDZ domain protein, here
      designated as IIP-1, insulin-like growth factor-1 (IGF-1) receptor-interacting
      protein-1, which binds to the IGF-1 receptor, but not to the related insulin
      receptor, and which is involved in the regulation of cell motility. The
      interaction between the IGF-1 receptor and IIP-1 as well as a splice variant IIP
      1/p26 was demonstrated in the yeast two-hybrid system. Using co-precipitation
      experiments, we confirmed the interaction in transfected cells as well as in
      vitro. Analysis of deletion mutants indicates that the PDZ domain of IIP-1
      mediates interaction with the C-terminal tail of the IGF-1 receptor (serine
      threonine-cysteine). This finding demonstrates that the C terminus of the IGF-1
      receptor acts as novel PDZ domain binding site. Immunofluorescence analysis
      revealed an overlapping localization of IIP-1 and the IGF-1 receptor in the
      breast cancer cell line MCF-7. A functional connection between IIP-1 and the IGF
      1 receptor is further supported by the finding that the level of expression of
      IIP-1 and the IGF-1 receptor strongly correlates in different normal and cancer
      cells. Furthermore, overexpression of IIP-1 resulted in an attenuation of
      migration of MCF-7 cells, which is one of the biological activities mediated by
      the IGF-1 signaling system.

PMID- 11445580
TI  - Transcriptional coactivator protein p300. Kinetic characterization of its histone
      acetyltransferase activity.
AB  - The p300/cAMP response element-binding protein-binding protein (CBP) family
      members include human p300 and cAMP response element-binding protein-binding
      protein, which are both important transcriptional coactivators and histone
      acetyltransferases. Although the role of these enzymes in transcriptional
      regulation has been extensively documented, the molecular mechanisms of p300 and
      CBP histone acetyltransferase catalysis are poorly understood. Herein, we
      describe the first detailed kinetic characterization of p300 using full-length
      purified recombinant enzyme. These studies have employed peptide substrates to
      systematically examine the substrate specificity requirements and the kinetic
      mechanism of this enzyme. The importance of nearby positively charged residues in
      lysine targeting was demonstrated. The strict structural requirement of the
      lysine side chain was shown. The catalytic mechanism of p300 was shown to follow
      a ping-pong kinetic pathway and viscosity experiments revealed that product
      release and/or a conformational change were likely rate-limiting in catalysis.
      Detailed analysis of the p300 selective inhibitor Lys-CoA showed that it
      exhibited slow, tight-binding kinetics.

PMID- 11445581
TI  - Molecular modeling of the extracellular domain of the RET receptor tyrosine
      kinase reveals multiple cadherin-like domains and a calcium-binding site.
AB  - Using bioinformatic tools, mutagenesis, and binding studies, we have investigated
      the structural organization of the extracellular region of the RET receptor
      tyrosine kinase, a functional receptor for glial cell line-derived neurotrophic
      factor (GDNF). Multiple sequence alignments of seven vertebrate sequences and one
      invertebrate RET sequence delineated four distinct N-terminal domains, each of
      about 110 residues, containing many of the consensus motifs of the cadherin fold.
      Based on these alignments and the crystal structures of epithelial and neural
      cadherins, we have generated molecular models of each of the four cadherin-like
      domains in the extracellular region of human RET. The modeled structures
      represent realistic models from both energetic and geometrical points of view and
      are consistent with previous observations gathered from biochemical analyses of
      the effects of Hirschsprung's disease mutations affecting the folding and
      stability of the RET molecule, as well as our own site-directed mutagenesis
      studies of RET cadherin-like domain 1. We have also investigated the role of
      Ca(2+) in ligand binding by RET and found that Ca(2+) ions are required for RET
      binding to GDNF but not for GDNF binding to the GFRalpha1 co-receptor. In
      agreement with these results, RET, but not GFRalpha1, was found to bind Ca(2+)
      directly. Our results indicate that the overall architecture of the extracellular
      region of RET is more closely related to cadherins than previously thought. The
      models of the cadherin-like domains of human RET represent valuable tools with
      which to guide future site-directed mutagenesis studies aimed at identifying
      residues involved in ligand binding and receptor activation.

PMID- 11445582
TI  - Analysis of the pore of the unusual major intrinsic protein channel, yeast Fps1p.
AB  - Fps1p is a glycerol efflux channel from Saccharomyces cerevisiae. In this
      atypical major intrinsic protein neither of the signature NPA motifs of the
      family, which are part of the pore, is preserved. To understand the functional
      consequences of this feature, we analyzed the pseudo-NPA motifs of Fps1p by site
      directed mutagenesis and assayed the resultant mutant proteins in vivo. In
      addition, we took advantage of the fact that the closest bacterial homolog of
      Fps1p, Escherichia coli GlpF, can be functionally expressed in yeast, thus
      enabling the analysis in yeast cells of mutations that make this typical major
      intrinsic protein more similar to Fps1p. We observed that mutations made in Fps1p
      to "restore" the signature NPA motifs did not substantially affect channel
      function. In contrast, when GlpF was mutated to resemble Fps1p, all mutants had
      reduced activity compared with wild type. We rationalized these data by
      constructing models of one GlpF mutant and of the transmembrane core of Fps1p.
      Our model predicts that the pore of Fps1p is more flexible than that of GlpF. We
      discuss the fact that this may accommodate the divergent NPA motifs of Fps1p and
      that the different pore structures of Fps1p and GlpF may reflect the
      physiological roles of the two glycerol facilitators.

PMID- 11445583
TI  - The ubiquitin-like protein FAT10 forms covalent conjugates and induces apoptosis.
AB  - FAT10 is a ubiquitin-like protein that is encoded in the major histocompatibility
      complex class I locus and is synergistically inducible with interferon-gamma and
      tumor necrosis factor alpha. The molecule consists of two ubiquitin-like domains
      in tandem arrangement and bears a conserved diglycine motif at its carboxyl
      terminus commonly used in ubiquitin-like proteins for isopeptide linkage to
      conjugated proteins. We investigated the function of FAT10 by expressing murine
      FAT10 in a hemagglutinin-tagged wild type form as well as a diglycine-deficient
      mutant form in mouse fibroblasts in a tetracycline-repressible manner. FAT10
      expression did not affect major histocompatibility complex class I cell surface
      expression or antigen presentation. However, we found that wild type but not
      mutant FAT10 caused apoptosis within 24 h of induction in a caspase-dependent
      manner as indicated by annexin V cell surface staining and DNA fragmentation.
      Wild type FAT10, but not its diglycine mutant, was covalently conjugated to thus
      far unidentified proteins, indicating that specific FAT10 activating and
      conjugating enzymes must be operative in unstimulated fibroblasts. Because FAT10
      expression causes apoptosis and is inducible with tumor necrosis factor alpha, it
      may be functionally involved in the programmed cell death mediated by this
      cytokine.

PMID- 11445584
TI  - Signaling complexes of the FERM domain-containing protein GRSP1 bound to ARF
      exchange factor GRP1.
AB  - GRP1 is a member of a family of proteins that contain a coiled-coil region, a
      Sec7 homology domain with guanosine nucleotide exchange activity for the ARF GTP
      binding proteins, and a pleckstrin homology domain at the C terminus. The
      pleckstrin homology domain of GRP1 binds phosphatidylinositol (3,4,5)
      trisphosphate and mediates the translocation of GRP1 to the plasma membrane upon
      agonist stimulation of PI 3-kinase activity. Using a (32)P-labeled GRP1 probe to
      screen a mouse brain cDNA expression library, we isolated a cDNA clone encoding a
      GRP1-binding partner (GRSP1) that exists as two different splice variants in
      brain and lung. The GRSP1 protein contains a FERM protein interaction domain as
      well as two coiled coil domains and may therefore function as a scaffolding
      protein. Mapping experiments revealed that the interaction of GRP1 and GRSP1
      occurs through the coiled coil domains in the two proteins. Immunodepletion
      experiments indicate that virtually all of the endogenous GRSP1 protein exists as
      a complex with GRP1 in lung. When co-expressed in Chinese hamster ovary cells
      expressing the human insulin receptor, both proteins display a diffuse,
      cytoplasmic localization. Acute translocation and co-localization of GRSP1 and
      GRP1 to ruffles in the plasma membrane was evident after insulin stimulation.
      These results identify GRSP1 as a novel member of GRP1 signaling complexes that
      are acutely recruited to plasma membrane ruffles in response to insulin receptor
      signaling.

PMID- 11445585
TI  - Atypical lambda/iota PKC conveys 5-lipoxygenase/leukotriene B4-mediated cross
      talk between phospholipase A2s regulating NF-kappa B activation in response to
      tumor necrosis factor-alpha and interleukin-1beta.
AB  - The transcription factor nuclear factor kappaB (NF-kappaB) plays crucial roles in
      a wide variety of biological functions such as inflammation, stress, and immune
      responses. We have shown previously that secretory nonpancreatic (snp) and
      cytosolic (c) phospholipase A(2) (PLA(2)) regulate NF-kappaB activation in
      response to tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta
      activation and that a functional coupling mediated by the 5-lipoxygenase (5-LO)
      metabolite leukotriene B(4) (LTB(4)) exists between snpPLA(2) and cPLA(2) in
      human keratinocytes. In this study, we have further investigated the mechanisms
      of PLA(2)-modulated NF-kappaB activation with respect to specific kinases
      involved in TNF-alpha/IL-1beta-stimulated cPLA(2) phosphorylation and NF-kappaB
      activation. The protein kinase C (PKC) inhibitors RO 31-8220, Go 6976, and a
      pseudosubstrate peptide inhibitor of atypical PKCs attenuated arachidonic acid
      release, cPLA(2) phosphorylation, and NF-kappaB activation induced by TNF-alpha
      or IL-1beta, thus indicating atypical PKCs in cPLA(2) regulation and
      transcription factor activation. Transfection of a kinase-inactive mutant of
      lambda/iotaPKC in NIH-3T3 fibroblasts completely abolished TNF-alpha/IL-1beta
      stimulated cellular arachidonic acid release and cPLA(2) activation assayed in
      vitro, confirming the role of lambda/iotaPKC in cPLA(2) regulation. Furthermore,
      lambda/iotaPKC and cPLA(2) phosphorylation was attenuated by phosphatidyinositol
      3-kinase (PI3-kinase) inhibitors, which also reduced NF-kappaB activation in
      response to TNF-alpha and IL-1beta, indicating a role for PI3-kinase in these
      processes in human keratinocytes. TNF-alpha- and IL-1beta-induced phosphorylation
      of lambda/iotaPKC was attenuated by inhibitors toward snpPLA(2) and 5-LO and by
      an LTB(4) receptor antagonist, suggesting lambda/iotaPKC as a downstream effector
      of snpPLA(2) and 5-LO/LTB(4) the LTB(4) receptor. Hence, lambda/iotaPKC regulates
      snpPLA(2)/LTB(4)-mediated cPLA(2) activation, cellular arachidonic acid release,
      and NF-kappaB activation induced by TNF-alpha and IL-1beta. In addition, our
      results demonstrate that PI3-kinase and lambda/iotaPKC are involved in cytokine
      induced cPLA(2) and NF-kappaB activation, thus identifying lambda/iotaPKC as a
      novel regulator of cPLA(2).

PMID- 11445586
TI  - An inhibitory role of the phosphatidylinositol 3-kinase-signaling pathway in
      vascular endothelial growth factor-induced tissue factor expression.
AB  - Vascular endothelial growth factor (VEGF) is not only essential for
      vasculogenesis and angiogenesis but is also capable of inducing tissue factor,
      the prime initiator of coagulation, in endothelial cells. In this study we have
      analyzed the VEGF-elicited pathways involved in the induction of tissue factor in
      human umbilical cord vein endothelial cells. Using specific low molecular weight
      inhibitors we could demonstrate a crucial role of the p38 and Erk-1/2 mitogen
      activated protein (MAP) kinases. In contrast, treatment with wortmannin or
      LY294002, inhibitors of phosphatidylinositol 3 (PI3)-kinase, resulted in a strong
      enhancement of the VEGF-induced tissue factor production, indicating a negative
      regulatory role of the PI3-kinase on tissue factor-inducing pathways.
      Accordingly, transduction with constitutively active Akt led to a reduction of
      VEGF-induced tissue factor production. Western blot analyses using antibodies
      specific for phosphorylated p38 showed an enhanced activation of this MAP kinase
      in human umbilical cord vein endothelial cells when stimulated with VEGF in the
      presence of wortmannin in comparison to either agent alone. Thus, the negative
      regulation of the PI3-kinase pathway on endothelial tissue factor activity can be
      explained at least in part by a suppression of this MAP kinase-signaling pathway.
      This is the first demonstration of a reciprocal relationship between procoagulant
      activity and the PI3-kinase-Akt signaling pathway, and it reveals a novel
      mechanism by which tissue factor expression can be controlled in endothelial
      cells.

PMID- 11445587
TI  - A yeast four-hybrid system identifies Cdk-activating kinase as a regulator of the
      XPD helicase, a subunit of transcription factor IIH.
AB  - To understand the role of the various components of TFIIH, a DNA
      repair/transcription factor, a yeast four-hybrid system was designed. When the
      ternary Cdk-activating kinase (CAK) complex composed of Cdk7, cyclin H, and MAT1
      was used as bait, the xeroderma pigmentosum (XP) D helicase of transcription
      factor IIH (TFIIH), among other proteins, was identified as an interacting
      partner. Deletion mutant analyses demonstrated that the coiled-coil and the
      hydrophobic domains of MAT1 interlink the CAK complex directly with the N
      terminal domain of XPD. Using immunoprecipitates from cells coinfected with
      baculoviruses, we further validated the bridging function of XPD, which anchors
      CAK to the core TFIIH. In addition we show that upon interaction with MAT1, CAK
      inhibits the helicase activity of XPD. This inhibition is overcome upon binding
      to p44, a subunit of the core TFIIH. It is not surprising that under these
      conditions some XPD mutations affect interactions not only with p44, but also
      with MAT1, thus preventing either the CAK inhibitory function within CAK.XPD
      and/or the role of CAK within TFIIH and, consequently, explaining the variety of
      the XP phenotypes.

PMID- 11445588
TI  - Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione
      peroxidases.
AB  - The GPX1, GPX2, and GPX3 genes of Saccharomyces cerevisiae have been reported
      previously to encode glutathione peroxidases (GPxs). We re-examined the sequence
      alignments of these proteins with GPxs from higher eukaryotes. Sequence
      identities, particularly with phospholipid hydroperoxide glutathione peroxidases
      (PHGPxs), were enhanced markedly by introduction to the yeast sequences of gaps
      that are characteristic of PHGPxs. PHGPx-like activity was detectable in extracts
      from wild-type S. cerevisiae and was diminished in extracts from gpx1 Delta, gpx2
      Delta, and gpx3 Delta deletion mutants; PHGPx activity was almost absent in a
      gpx1 Delta/gpx2 Delta/gpx3 Delta triple mutant. Studies with cloned GPX1, GPX2,
      and GPX3 expressed heterologously in Escherichia coli confirmed that these genes
      encode proteins with PHGPx activity. An S. cerevisiae gpx1 Delta/gpx2 Delta/gpx3
      Delta mutant was defective for growth in medium supplemented with the oxidation
      sensitive polyunsaturated fatty acid linolenate (18:3). This sensitivity to 18:3
      was more marked than sensitivity to H(2)O(2). Unlike H(2)O(2) toxicity, delayed
      toxicity of 18:3 toward gpx1 Delta/gpx2 Delta/gpx3 Delta cells was correlated
      with the gradual incorporation of 18:3 into S. cerevisiae membrane lipids and was
      suppressible with alpha-tocopherol, an inhibitor of lipid peroxidation. The
      results show that the GPX genes of S. cerevisiae, previously reported to encode
      GPxs, encode PHGPxs (PHGPx1, PHGPx2, and PHGPx3) and that these enzymes protect
      yeast against phospholipid hydroperoxides as well as nonphospholipid peroxides
      during oxidative stress. This is the first report of an organism that expresses
      PHGPx from more than one gene and produces PHGPx in the absence of a GPx.

PMID- 11445589
TI  - Assembly and enzymatic properties of the catalytic domain of human complement
      protease C1r.
AB  - The catalytic properties of C1r, the protease that mediates activation of the C1
      complex of complement, are mediated by its C-terminal region, comprising two
      complement control protein (CCP) modules followed by a serine protease (SP)
      domain. Baculovirus-mediated expression was used to produce fragments containing
      the SP domain and either 2 CCP modules (CCP1/2-SP) or only the second CCP module
      (CCP2-SP). In each case, the wild-type species and two mutants stabilized in the
      proenzyme form by mutations at the cleavage site (R446Q) or at the active site
      serine residue (S637A), were produced. Both wild-type fragments were recovered as
      two-chain, activated proteases, whereas all mutants retained a single-chain,
      proenzyme structure, providing the first experimental evidence that C1r
      activation is an autolytic process. As shown by sedimentation velocity analysis,
      all CCP1/2-SP fragments were dimers (5.5-5.6 S), and all CCP2-SP fragments were
      monomers (3.2-3.4 S). Thus, CCP1 is essential to the assembly of the dimer, but
      formation of a stable dimer is not a prerequisite for self-activation. Activation
      of the R446Q mutants could be achieved by extrinsic cleavage by thermolysin,
      which cleaved the CCP2-SP species more efficiently than the CCP1/2-SP species and
      yielded enzymes with C1s-cleaving activities similar to their active wild-type
      counterparts. C1r and its activated fragments all cleaved C1s, with relative
      efficiencies in the order C1r < CCP1/2-SP < CCP2-SP, indicating that CCP1 is not
      involved in C1s recognition.

PMID- 11445590
TI  - Changing a single amino acid residue switches processive and non-processive
      behavior of Aspergillus niger endopolygalacturonase I and II.
AB  - Processivity, also known as multiple attack on a single chain, is a feature
      commonly encountered only in enzymes in which the substrate binds in a tunnel.
      However, of the seven Aspergillus niger endopolygalacturonases, which have an
      open substrate binding cleft, four enzymes show processive behavior, whereas the
      other endopolygalacturonases are randomly acting enzymes. In a previous study
      (Benen, J.A.E., Kester, H.C.M., and Visser, J. (1999) Eur. J. Biochem. 259, 577
      585) we proposed that the high affinity for the substrate of subsite -5 of
      processive endopolygalacturonase I constitutes the origin of the multiple attack
      behavior. Based on primary sequence alignments of A. niger endopolygalacturonases
      and three-dimensional structure analysis of endopolygalacturonase II, an arginine
      residue was identified in the processive enzymes at a position commensurate with
      subsite -5, whereas a serine residue was present at this position in the non
      processive enzymes. In endopolygalacturonase I mutation R95S was introduced, and
      in endopolygalacturonase II mutation S91R was introduced. Product progression
      analysis on polymer substrate and bond cleavage frequency studies using
      oligogalacturonides of defined chain length for the mutant enzymes revealed that
      processive/non-processive behavior is indeed interchangeable by one single amino
      acid substitution at subsite -5, Arg-->Ser or Ser-->Arg.

PMID- 11445591
TI  - The N-terminal zinc finger of the erythroid transcription factor GATA-1 binds
      GATC motifs in DNA.
AB  - The mammalian transcription factor GATA-1 is required for normal erythroid and
      megakaryocytic development. GATA-1 contains two zinc fingers, the C-terminal
      finger, which is known to bind (A/T)GATA(A/G) motifs in DNA and the N-finger,
      which is important for interacting with co-regulatory proteins such as Friend of
      GATA (FOG). We now show that, like the C-finger, the N-finger of GATA-1 is also
      capable of binding DNA but recognizes distinct sequences with the core GATC. We
      demonstrate that the GATA-1 N-finger can bind these sequences in vitro and that
      in cellular assays, GATA-1 can activate promoters containing GATC motifs.
      Experiments with mutant GATA-1 proteins confirm the importance of the N-finger,
      as the C-finger is not required for transactivation from GATC sites. Recently
      four naturally occurring mutations in GATA-1 have been shown to be associated
      with familial blood disorders. These mutations all map to the N-finger domain. We
      have investigated the effect of these mutations on the recognition of GATC sites
      by the N-finger and show that one mutation R216Q abolishes DNA binding, whereas
      the others have only minor effects.

PMID- 11445592
TI  - Heat shock protein accumulation is upregulated in a long-lived mutant of
      Caenorhabditis elegans.
AB  - We present evidence for elevated levels of heat shock protein 16 (HSP16) in an
      intrinsically thermotolerant, long-lived strain of Caenorhabditis elegans during
      and after heat stress. Mutation of the age-1 gene, encoding a
      phosphatidylinositol 3-kinase catalytic subunit, results in both extended life
      span (Age) and increased intrinsic thermotolerance (Itt) in adult hermaphrodites.
      We subjected age-synchronous cohorts of worms to lethal and nonlethal thermal
      stress and observed the accumulation of a small (16-18 kd) heat-shock-specific
      polypeptide detected by an antibody raised against C. elegans HSP16. Strains
      carrying the mutation hx546 consistently accumulated HSP16 to higher levels than
      a wild-type strain. Significantly, overaccumulation of HSP16 in the age-1(hx546)
      strain following heat was observed throughout the adult life span. A chimeric
      transgene containing the Escherichia coli beta-galactosidase gene fused to a C.
      elegans HSP16-41 transcriptional promoter was introduced into wild-type and age
      1(hx546) backgrounds. Heat-inducible expression of the transgene was elevated in
      the age-1(hx546) strain compared with the wild-type strain under a wide variety
      of heat shock and recovery conditions. These observations are consistent with a
      model in which Age mutations exhibit thermotolerance and extended life span as a
      result of elevated levels of molecular chaperones.

PMID- 11445593
TI  - Age-related changes in the regulation of autophagic proteolysis in rat isolated
      hepatocytes.
AB  - During intervals between meals, autophagy is a major source of nutrients and may
      remove damaged organelles and membranes. Age-related changes in the regulation of
      autophagic proteolysis were studied by monitoring the rate of valine release from
      liver cells of 2-, 6-, 12-, 18-, and 24-month-old male Sprague-Dawley rats fed ad
      libitum, and incubated in vitro with added amino acids and 10(-7) M of insulin or
      glucagon. The maximum rate of proteolysis and its maximum inhibition by amino
      acids were reached at 6 months and declined thereafter. In contrast, the rate of
      protein degradation in the presence of high concentrations of amino acids was not
      affected by aging. The inhibitor effect of insulin was additive to that of amino
      acids and was not altered significantly by age. The conclusion is that altered
      regulation of autophagic proteolysis decreases susceptibility of older cells to
      lysosomal degradation, and it may lead to the accumulation of altered organelles
      and membranes.

PMID- 11445594
TI  - Predictors of healthy brain aging.
AB  - To determine if superior health at old age protects against cognitive impairment
      (CI) and Alzheimer's disease (AD), we prospectively studied 100 optimally healthy
      oldest-old (> or =85 years) individuals. Initially, subjects represented the top
      3% of the oldest old for health. During 5.6 +/- 0.3 years of follow-up, 34
      subjects developed CI, and 23 progressed to AD. By age 100, probability of CI and
      AD were.65 +/-.09 and.49 +/-.10. Median onset age was 97 years for CI and 100 for
      AD. Clearly, superior health at old age does not guarantee protection against
      cognitive decline. Lifetime risks were similar to the general population but
      onset ages were later, suggesting factors that delay onset are key to improving
      cognitive health in the elderly. In this population, absence of apolipoprotein E
      epsilon4 and male gender were associated with delayed onset, whereas estrogen use
      and education had no detectable effect on cognitive outcome.

PMID- 11445595
TI  - Resistance training in patients with peripheral arterial disease: effects on
      myosin isoforms, fiber type distribution, and capillary supply to skeletal
      muscle.
AB  - The purpose of this study was to investigate the effects of a progressive
      resistance training program on myosin heavy chain isoform expression, fiber type,
      and capillarization in patients with symptomatic peripheral arterial disease.
      Patients were randomized to either a training group (n = 11, mean +/- SD, 70 +/-
      6 years, 4 men, 7 women) or a control group (n = 9, 66 +/- 6 years, 5 men, 4
      women). The training sessions were completed 3 times/week, using 2 sets of
      various exercises, each performed for 8-15 repetitions. Muscle biopsies were
      obtained before and after 24 weeks from the medial gastrocnemius. Following the
      24-week training program, the training group had significantly decreased the
      percentage of myosin heavy chain type IIB. The proportion of type IIB/AB fibers
      as measured by using myosin adenosine triphosphatase histochemistry decreased
      significantly in the training group. There were significant increases in type I
      and type II fiber areas, and capillary density also increased significantly in
      the training group. There were significant increases in 10 repetition maximum leg
      press and calf press strengths in the trained subjects. There were no significant
      changes in any of the measurements in the control group. It is concluded that
      progressive resistance training results in significant increases in muscle
      strength and alters skeletal muscle composition of subjects with peripheral
      arterial disease.

PMID- 11445596
TI  - Melatonin increases both life span and tumor incidence in female CBA mice.
AB  - From the age of 6 months until their natural deaths, female CBA mice were given
      melatonin with their drinking water (20 mg/l) for 5 consecutive days every month.
      Intact mice served as controls. The results of this study show that the
      consumption of melatonin did not significantly influence food consumption, but it
      did increase the body weight of older mice; it did not influence physical
      strength or the presence of fatigue; it decreased locomotor activity and body
      temperature; it inhibited free radical processes in serum, brain, and liver; it
      slowed down the age-related switching-off of estrous function; and it increased
      life span. However, we also found that treatment with the used dose of melatonin
      increased spontaneous tumor incidence in mice. For this reason, we concluded that
      it would be premature to recommend melatonin as a geroprotector for long-term
      use.

PMID- 11445597
TI  - "Who's taking your 5th vital sign?".

PMID- 11445598
TI  - Impact of pain on disability among older Mexican Americans.
AB  - BACKGROUND: Joint pain is a very common complaint among elderly persons and may
      lead to functional disability. The purpose of this study is to estimate the
      prevalence of self-reported pain on weight bearing and its impact on the 2-year
      incidence of limitation in lower-body activities of daily living (ADL) in
      initially nondisabled Mexican American elderly subjects. METHODS: We studied a
      probability sample of 2167 noninstitutionalized Mexican American men and women
      aged 65 or older residing in five Southwestern states. Subjects were asked about
      pain on weight bearing, ADL, depressive symptomatology, and the presence of
      chronic diseases. The body mass index was computed using measured height and
      weight. Finally, a three-task (tandem balance, 8-foot walk, and repeated chair
      stands), performance-based, lower-body function test was performed. RESULTS: The
      overall prevalence of pain on weight bearing in the sample was 31.9%, with 37.7%
      for women versus 24.0% for men (p <.001). The most prevalent sites of pain were
      knees (14.7%), followed by ankle/feet (12.1%). In a logistic regression analysis,
      pain was a significant independent predictor of subsequent disability and of the
      inability to perform tandem balance, 8-foot walk, and repeated chair stands.
      CONCLUSIONS: Pain on weight bearing is prevalent among older Mexican Americans
      and is a major independent risk factor for subsequent disability.

PMID- 11445599
TI  - Accuracy and bias of licensed practical nurse and nursing assistant ratings of
      nursing home residents' pain.
AB  - BACKGROUND: This study evaluated the accuracy of licensed practical nurses' (LPN)
      and nursing assistants' (NA) Minimum Data Set (MDS) pain ratings of nursing home
      residents and evaluated the bias in pain ratings associated with residents' race,
      gender, mental status, function, depression, or disruptive behavior. METHODS:
      Data were obtained on the same day directly from residents, LPNs, and NAs by
      trained interviewers in two safety-net nursing homes. A total of 252 residents
      were included in this study: 79% were Black, and 60% were men. MDS items J2a and
      J2b evaluated pain frequency and pain intensity during the last 7 days (weekly
      pain frequency and weekly pain intensity). A parallel question evaluated pain
      intensity on the day of the interview (daily pain intensity). MDS data were
      obtained for the MDS Cognition Scale, the MDS Activities of Daily Living-Long
      Form Scale, the MDS Depression Rating Scale, and the MDS Disruptive Behavior
      Scale. RESULTS: Kappa coefficients documented fair to good resident-LPN (K
      =.70,.56, and.50) and resident-NA (K =.72,.58, and.60) agreement for weekly pain
      frequency, weekly pain intensity, and daily pain intensity ratings. LPNs and NAs
      underestimated residents' weekly pain frequency (p <.001 for LPNs, and p <.001
      for NAs), weekly pain intensity (p <.001 for LPNs, and p <.001 for NAs), and
      daily pain intensity (p <.001 for LPNs, and p =.002 for NAs). LPNs underestimated
      weekly and daily pain intensity more than NAs did (p =.016 for weekly pain
      intensity, and p =.035 for daily pain intensity). LPN and NA pain ratings were
      not biased by resident race, gender, mental status, function, depression, or
      disruptive behavior. CONCLUSIONS: Results documented that (i) LPNs and NAs
      underestimated residents' pain frequency and pain intensity, (ii) NAs were more
      accurate than LPNs for pain intensity, and (iii) resident characteristics did not
      bias LPN or NA pain ratings.

PMID- 11445600
TI  - Have we oversold the benefit of late-life exercise?
AB  - BACKGROUND: Increasing exercise among older adults to improve function and
      prevent or decrease disability is widely promoted in developed countries. This
      review seeks to critically evaluate the degree to which existing scientific
      evidence supports these claims. METHODS: A literature review was performed in
      Medline and Best Evidence databases for the years 1985 to 2000. Experimental and
      quasi-experimental aerobic and resistance exercise interventions were reviewed
      for impairment, function, and disability outcomes. The impact of exercise on
      specific impairments, functions, and disabilities was examined by summarizing the
      findings reported across all studies. RESULTS: Thirty-one studies were
      identified. Impairment and functional outcomes were reported in 97% and 81% of
      the studies, respectively; half of the studies examined disability outcomes. The
      most consistent positive effects of late-life exercise were observed in strength,
      aerobic capacity, flexibility, walking, and standing balance, with over half of
      the studies that examined these outcomes finding positive effects. Of the studies
      that examined physical, social, emotional, or overall disability outcomes, most
      found no improvements. In the five studies that reported reduced physical
      disability, the effect sizes ranged from .23 to .88. CONCLUSIONS: Late-life
      exercise clearly improves strength, aerobic capacity, flexibility, and physical
      function. Existing scientific evidence, however, does not support a strong
      argument for late-life exercise as an effective means of reducing disability.
      This may be due, in part, to methodological limitations in studies that have
      examined disability outcomes. On the other hand, the theoretical basis of
      interventions aimed at reducing disability may need to extend beyond exercise and
      address behavioral and social factors.

PMID- 11445601
TI  - Atypical presentation of scabies among nursing home residents.
AB  - BACKGROUND: Scabies epidemics are not uncommon in nursing homes. Effective
      treatment is enhanced by prompt clinical diagnosis and early intervention. The
      clinical presentation of scabies may vary in older, immunocompromised or
      cognitively impaired persons. METHODS: We performed a retrospective study of all
      residents diagnosed with scabies in a multilevel long-term care geriatric
      facility. The duration of the outbreak was from May to September 2000. RESULTS:
      Fifteen residents contracted scabies during the outbreak. All affected residents
      had predominantly truncal lesions. Twelve residents had diffuse erythematous,
      papulosquamous lesions. Pruritus occurred in only 5 residents. Three residents
      with severe dementia and notably impaired functional status failed to respond to
      Permethrin cream (5%). All 3 residents responded to treatment with oral
      Ivermectin. CONCLUSION: Older nursing home residents with scabies may present
      with atypical skin lesions. Residents with cognitive impairment and restricted
      mobility may be treatment resistant. The diagnosis of scabies should be
      considered in any nursing home resident with an unexplained generalized rash.
      Residents with dementia and severe functional impairment that fail to respond to
      Permethrin cream (5%) may benefit from treatment with oral Ivermectin.

PMID- 11445602
TI  - Mechanisms leading to a fall from an induced trip in healthy older adults.
AB  - BACKGROUND: Tripping is a leading cause of falls in older adults, often resulting
      in serious injury. Although the requirements for recovery from a trip are well
      characterized, the mechanisms whereby trips by older adults actually result in
      falls are not known. This study sought to identify such mechanisms. METHODS:
      Trips were induced during gait in 79 healthy, community-dwelling, safety
      harnessed, older adults (50 women) using a concealed, mechanical obstacle.
      Kinematic and kinetic variables describing the recovery attempts were compared
      between those who fell and those who recovered. Subjects were analyzed according
      to the recovery strategy employed (lowering vs elevating) and the time of the
      "fall" (during step vs after step). RESULTS: Three apparent mechanisms of falling
      were identified. For a lowering strategy, during-step falls were associated with
      a faster walking speed at the time of the trip (91% +/- 8% vs 68% +/- 11% body
      height [bh] per second; p <.001) and delayed support limb loading (267 +/- 49
      milliseconds vs 160 +/- 39 milliseconds; p <.001). After-step falls were
      associated with a more anterior head-arms-torso center of mass at the time of the
      trip (6.2 +/- 1.3 degrees vs 0.2 +/- 4.4 degrees; p <.01), followed by excessive
      lumbar flexion and buckling of the recovery limb. The elevating strategy fall was
      associated with a faster walking speed (93% vs 68% +/- 11% bh per second; p
      <.001) followed by excessive lumbar flexion. CONCLUSIONS: Walking quickly may be
      the greatest cause of falling following a trip in healthy older adults. An
      anterior body mass carriage, accompanied by back and knee extensor weakness, may
      also lead to falls following a trip. Deficient stepping responses did not
      contribute to the falls.

PMID- 11445603
TI  - Trunk sway measures of postural stability during clinical balance tests: effects
      of age.
AB  - BACKGROUND: The major disadvantage of current clinical tests that screen for
      balance disorders is a reliance on an examiner's subjective assessment of
      equilibrium control. To overcome this disadvantage we investigated, using
      quantified measures of trunk sway, age-related differences of normal subjects for
      commonly used clinical balance tests. METHODS: Three age groups were tested:
      young (15-25 years; n = 48), middle-aged (45-55 years; n = 50) and elderly (65-75
      years; n = 49). Each subject performed a series of fourteen tasks similar to
      those included in the Tinetti and Clinical Test of Sensory Interaction in Balance
      protocols. The test battery comprised stance and gait tasks performed under
      normal, altered visual (eyes closed), and altered proprioceptive (foam support
      surface) conditions. Quantification of trunk sway was performed using a system
      that measured trunk angular velocity and position in the roll (lateral) and pitch
      (fore-aft) planes at the level of the lower back. Ranges of sway amplitude and
      velocity were examined for age-differences with ANOVA techniques. RESULTS: A
      comparison between age groups showed several differences. Elderly subjects were
      distinguished from both middle-aged and young subjects by the range of trunk
      angular sway and angular velocity because both were greater in roll and pitch
      planes for stance and stance-related tasks (tandem walking). The most significant
      age group differences (F = 30, p <.0001) were found for standing on one leg on a
      normal floor or on a foam support surface with eyes open. Next in significance
      was walking eight tandem steps on a normal floor (F = 13, p <.0001). For gait
      tasks, such as walking five steps while rotating or pitching the head or with
      eyes closed, pitch and roll velocity ranges were influenced by age with middle
      aged subjects showing the smallest ranges followed by elderly subjects and then
      young subjects (F = 12, p <.0001). Walking over a set of low barriers also
      yielded significant differences between age groups for duration and angular sway.
      In contrast, task duration was the only variable significantly influenced when
      walking up and down a set of stairs. An interesting finding for all tasks was the
      different spread of values for each population. Population distributions were
      skewed for all ages and broadened with age. CONCLUSIONS: Accurate measurement of
      trunk angular sway during stance and gait tasks provides a simple way of reliably
      measuring changes in balance stability with age and could prove useful when
      screening for balance disorders of those prone to fall.

PMID- 11445604
TI  - Instrumental activities of daily living as a potential marker of frailty: a study
      of 7364 community-dwelling elderly women (the EPIDOS study).
AB  - BACKGROUND: A number of clinical conditions have been shown to be associated with
      frailty in elderly people. We hypothesized that incapacities on the Instrumental
      Activities of Daily Living (IADLs) scale could make it possible to identify this
      population. We investigated the associations between IADL incapacities and the
      various known correlates of frailty in a cohort of community-dwelling elderly
      women. METHODS: Cross-sectional analysis was carried out on the data from 7364
      women aged over 75 years (EPIDOS Study). The IADL was the dependent variable.
      Sociodemographic, medical, and psychological performance measures were obtained
      during an assessment visit. Falls in the previous 6 months and fear of falling
      were also ascertained. Body composition was measured by dual-energy x-ray
      absorptiometry. The factors associated with disability in at least one IADL were
      included in a logistic regression model. RESULTS: Thirty-two percent of the
      population studied had disability in at least one IADL item. This group was
      significantly older (81.7 +/- 4.1 yr vs 79.8 +/- 3.4 yr), had more frequent
      histories of heart disease, stroke, depression or diabetes, and was socially less
      active (p =.001). These associations persisted after multivariate analysis.
      Cognitive impairment as assessed by the Pfeiffer test (Pfeiffer score <8) was
      closely associated with disabilities on the IADL (OR 3.101, 95% confidence
      interval [CI] 2.19-4.38). Falls and fear of falling were also more frequent in
      the group of women with an abnormal IADL (p =.001) but only fear of falling
      remained significantly associated with incapacities on at least one IADL item
      after logistic regression (OR 1.47, 95% CI 1.28-1.69). Women with disability on
      at least one IADL item also had lower bone mineral density, this was independent
      of the other factors. CONCLUSION: Our results confirmed that women with
      disability on at least one IADL item are frailer because they had more associated
      disorders, poorer cognitive function and more frequent falls. Disabilities on
      this scale could be a good tool for identifying individuals at risk of frailty
      among elderly persons living at home and in apparent good health. This finding
      requires confirmation by longitudinal studies.

PMID- 11445605
TI  - Impaired balance and higher prevalence of falls in subjects with intermittent
      claudication.
AB  - BACKGROUND: The purpose of this study was to determine whether peripheral
      arterial disease (PAD) subjects have impaired balance and a higher prevalence of
      falls than non-PAD controls and to determine whether balance and falls are
      related to the severity of PAD and functional status. METHODS: A total of 367 PAD
      subjects (aged 68 +/- 1 years; mean +/- SEM) and 458 non-PAD controls (aged 67 +/
      1 years) were recruited. Unipedal stance time, history of ambulatory stumbling
      and unsteadiness, and history of falling were recorded. Additionally, subjects
      were characterized on age, ankle/brachial index (ABI), anthropometry, measured
      and self-reported ambulatory function, and monitored daily physical activity.
      RESULTS: Unipedal stance time was 28% shorter ( p <.001) in the PAD subjects than
      in the non-PAD controls (15.9 +/- 0.9 vs 22.1 +/- 1.0). History of ambulatory
      stumbling and unsteadiness was 86% more prevalent ( p <.001) in the PAD group
      (150/367 = 41%) than in the controls (101/458 = 22%), and history of falling was
      73% more prevalent ( p <.001) in the PAD subjects (95/367 = 26%) than in the
      controls (69/458 = 15%). Within the PAD group, 6-minute walk distance, self
      reported ambulatory function, and daily physical activity were significantly
      related to the balance and falling measures ( p <.05), whereas ABI was unrelated
      ( p >.05). CONCLUSIONS: Compared with the controls, PAD subjects with
      intermittent claudication had impaired balance and a greater likelihood of
      falling, both of which were associated with ambulatory function and daily
      physical activity.

PMID- 11445606
TI  - Gender differences in self-concept and psychological well-being in old age: a
      meta-analysis.
AB  - Because of women's higher risk of being widowed, having health problems, and
      needing care, one might expect them to have a more negative self-concept and
      lower subjective well-being (SWB). However, women may also have greater access to
      sources of SWB (e.g., relations to adult children) and may engage in processes to
      protect the self (e.g., lowered aspirations). Meta-analysis was used to
      synthesize findings from 300 empirical studies on gender differences in life
      satisfaction, happiness, self-esteem, loneliness, subjective health, and
      subjective age in late adulthood. Older women reported significantly lower SWB
      and less positive self-concept than men on all measures, except subjective age,
      although gender accounted for less than 1% of the variance in well-being and self
      concept. Smaller gender differences in SWB were found in younger than in older
      groups. Statistically controlling for gender differences in widowhood, health,
      and socioeconomic status decreased gender differences in SWB. Cohort differences
      in SWB are reported as well.

PMID- 11445607
TI  - Age differences in stress, social resources, and well-being in middle and older
      age.
AB  - The present study examines the interrelationships among the constructs of social
      resources, stress, and well-being in middle-aged and older adults. Two samples of
      489 middle-aged adults (41-43 years) and 449 older adults (61-63 years) from the
      Interdisciplinary Longitudinal Study of Adult Development were compared with
      respect to the availability of social resources, levels of stress, and well
      being. The data were used to construct separate structural equation models
      explaining the influence of stress and social resources on well-being in the two
      groups. The results indicate higher levels of health-related stress and similar
      levels of social resources in the older group. Structural equation models and
      examination of total and indirect effects confirmed that a stress-suppression
      model has the best fit in explaining the interrelationships between stress,
      social resources, and well-being. There was a strong effect of stress on well
      being, no direct effect of social resources on well-being, and a mediating effect
      of stress on well-being. The relative contributions of stress and resources to
      well-being were comparable between age groups.

PMID- 11445608
TI  - Coping-with-hearing-loss model for older adults.
AB  - We proposed a coping-with-hearing-loss model that explains how hearing loss,
      psychosocial factors (i.e., attitudes about aging, personal adjustment to hearing
      loss, and perceived social support), and perceived strategy effectiveness affect
      the use of adaptive and maladaptive strategies. Adaptive strategies are behaviors
      that improve communication (i.e., asking others to repeat). Maladaptive
      strategies are coping behaviors that do not promote communication (i.e.,
      pretending to understand the conversation). Nonaudiological variables were more
      important than physical hearing loss (as measured by an audiological examination)
      in predicting coping behaviors for hearing loss. The use of adaptive strategies
      was predicted by perceived strategy effectiveness. The use of maladaptive
      strategies was predicted by perceived effectiveness of the strategies to cope
      with hearing loss in daily life, poor adjustment to hearing loss, and poor social
      support. The results suggest that psychosocial issues may need to be addressed
      when older adults have difficulties coping with their hearing loss.

PMID- 11445609
TI  - Olfactory functioning and cognitive abilities: a twin study.
AB  - A Swedish version of the National Geographic Smell Survey (Wysocki and Gilbert
      1989) was completed by 227 twin pairs from the Swedish Adoption/Twin Study of
      Aging. Twins ranged in age from 45 to 89 years. Quantitative genetic analysis of
      four measures of olfactory functioning indicated moderate heritability for odor
      identification and perceived intensity and nonsignificant heritability for odor
      detection and perceived pleasantness. Bivariate analyses revealed that the
      relationship between odor identification and measures of verbal ability was
      primarily genetically mediated. The results provided further support for the
      hypothesis that odor identification and verbal ability in general tap the same
      cognitive domain (Larsson 1997).

PMID- 11445610
TI  - Reactions of older employees to organizational downsizing: the role of gender,
      job level, and time.
AB  - This panel study examined the reactions of 187 federal government employees aged
      45 and older during the initial phase of a large-scale downsizing and 20 months
      later. There were few significant differences in the reactions of older men and
      women. Respondents in management positions reported significantly more positive
      attitudes toward their job and the organization than did respondents in
      nonmanagement jobs. Compared with the initial phase of the downsizing,
      respondents reported a significant decrease in commitment to the organization 20
      months later. For the two dimensions of job insecurity, perceived threat of job
      loss decreased, whereas sense of powerlessness over decisions affecting the
      future of one's job increased. A major area of concern for management is the low
      level of organizational trust and morale reported by the respondents at both time
      periods.

PMID- 11445611
TI  - Diagnostic attributions versus labeling: impact of Alzheimer's disease and major
      depression diagnoses on emotions, beliefs, and helping intentions of family
      members.
AB  - Labeling theory suggests that applying disease labels to behavior may serve to
      medicalize deviance and produce stigma. In contrast, attribution theory suggests
      that this practice may evoke sympathetic responses. Female undergraduates (N =
      221) read vignettes describing an older parent exhibiting inappropriate behavior
      in a social situation, with diagnostic label (Alzheimer's disease, major
      depression, no label), personal congruence of the behavior (congruent,
      incongruent, no information), and parent gender manipulated across participants.
      Participants rated their emotional responses, attributions, and willingness to
      help. The Alzheimer's disease label, and to a lesser extent the major depression
      label, produced more sympathy toward the parent, less blame, and greater
      willingness to help, indicating that the provision of these labels may facilitate
      compassionate attitudes and enhanced caregiving toward older adults. However,
      participants reported greater anger and higher personality attributions toward
      fathers than mothers, suggesting that the influence of parent gender on potential
      caregivers' reactions warrants further attention.

PMID- 11445612
TI  - Self-rated health and mortality among black and white adults: examining the
      dynamic evaluation thesis.
AB  - OBJECTIVES: Many studies of self-rated health show that it is a reliable
      predictor of mortality even when controlling for health-related variables and
      status characteristics. According to previous research, one reason for the
      consistent finding is that self-ratings of health represent judgments of health
      trajectories. Although self-ratings of health may be dynamic perceptions of
      health, relatively few studies have systematically examined this possibility.
      METHODS: This study reexamines the prognostic value of self-ratings of health on
      mortality with data from 20 years of the National Health and Nutrition
      Examination Survey-I Epidemiologic Follow-up Study (N = 6,833). Special attention
      is given to differences between White and African Americans. RESULTS: Results
      indicate that event history models of mortality with self-rated health treated as
      a time-dependent covariate are superior to those treating it as a baseline
      predictor only-the latter are likely to underestimate the effect. Moreover, self
      ratings of health predict mortality for African Americans only when treated as a
      time-dependent covariate. DISCUSSION: The results suggest that self-ratings of
      health are sensitive to declines in physical health, especially those associated
      with terminal drop. The analysis also demonstrates the importance of using
      dynamic models for studying the link between self-rated health and mortality if
      data from multiple observation points are available.

PMID- 11445613
TI  - Persistent, consistent, widespread, and robust? Another look at recent trends in
      old-age disability.
AB  - OBJECTIVE: The purpose of this study was to provide new evidence on disability
      trends among elderly persons from 1982 to 1996. METHODS: The sample includes
      124,949 participants aged 70 and older in the 1982-1996 National Health Interview
      Surveys. Logistic analysis was used to estimate the trend in disability
      prevalence after controlling for various sociodemographic factors. RESULTS: We
      found that: (a) the prevalence of disability has declined, but the gains did not
      persist throughout the entire period or accelerate over time; (b) only routine
      care disability has declined, whereas more severe personal care disability shows
      no improvements; (c) estimates are robust to the exclusion of the nursing home
      population but may be sensitive to growth in the assisted living population; (d)
      estimates of decline in disability prevalence are fairly consistent across five
      national surveys; (e) gains have been concentrated among the most educated
      elderly persons; and (f) gains in education appear to be an important confounder
      of the improvements. DISCUSSION: Evidence from several surveys using various
      measures indicates that disability has declined among elderly persons.
      Determining the causes of the improvements should be a high priority in future
      research efforts.

PMID- 11445614
TI  - Informal costs of dementia care: estimates from the National Longitudinal
      Caregiver Study.
AB  - OBJECTIVES: The purpose of the study was to examine on a national level the
      informal costs of caring for elderly community-dwelling male veterans with
      dementia by female caregivers and the relationships between informal costs and
      disease severity, and between informal costs and dementia problem behaviors.
      METHODS: Female primary caregivers were drawn from the first wave (N = 2043) of
      the National Longitudinal Caregiver Study, a survey of informal caregivers of
      elderly male veterans diagnosed with probable Alzheimer's disease or vascular
      dementia. Cost measures include the following four items: value of caregiving
      time, caregiver's lost income, out-of-pocket expenditures for formal caregiving
      services, and caregiver's excess health costs. Disease severity was indexed by
      the number of impairments in activities of daily living. Patient's problem
      behaviors were measured using the Behavior Rating Scale-Dementia. RESULTS: The
      annual cost of providing informal care to elderly community-dwelling veterans
      with dementia was estimated to be $18,385 per patient in 1998. The larger
      components of this cost are caregiving time ($6,295) and caregiver's lost
      earnings ($10,709). All aspects of costs increase with disease severity and
      problem behavior. Most of this cost increase derives from the increased
      caregiving time required for the provision of physical care. DISCUSSION: This
      study provides a comprehensive estimate of the excess costs that result from
      providing informal dementia care in the community. Unlike previous studies, our
      estimates excluded costs that caregivers would have incurred if they had not been
      caregivers. Therefore, results reported here reflect only costs due to informal
      dementia care.

PMID- 11445615
TI  - Social predictors of recovery in late middle-aged and older persons after injury
      to the extremities: a prospective study.
AB  - OBJECTIVES: The impact of educational level and social support on short-term and
      long-term recovery of activities of daily living and instrumental activities of
      daily living after injuries to the extremities was examined in a prospective
      study concerning late middle-aged and older persons. METHODS: Patients (N = 171)
      who had sustained fall-related injuries (hip fractures, other fractures, or
      sprains and dislocations) participated in the study. Disability scores were
      collected at baseline (before the injury) and 8 weeks, 5 months, and 12 months
      after the injury. The authors used analysis of variance to assess possible
      differences between 3 levels of education and social support with respect to
      changes in disability scores from baseline to the 3 follow-up measurements while
      adjusting for covariates. RESULTS: Preinjury assessed educational level or social
      support did not play a role in short-term changes in disability. In the long term
      (5 and 12 months after the injury), recovery was significantly associated with
      social support: Those with higher levels of support had a better recovery.
      Although patients with high levels of education most closely approached their pre
      event level of disability as well, differences did not reach statistical
      significance. Short-term changes in disability appeared to be determined by the
      severity of the injury. Social support began to influence recovery only when the
      impact of severity expired. DISCUSSION: Patients recovering from fall-related
      injuries who had reported high levels of social support before their injury had
      recovered better at 5 and 12 months. Encouragement and special attention given by
      health professionals to maintain social support may be beneficial for
      rehabilitation after fall-related injuries in older persons.

PMID- 11445616
TI  - Psychological adjustment to sudden and anticipated spousal loss among older
      widowed persons.
AB  - OBJECTIVES: This study examined if older adults' psychological adjustment to
      widowhood varies based on whether the death was sudden or anticipated and if
      these effects are mediated by death context characteristics (e.g., predeath
      caregiving, nursing home use, spouse's age at death, and couple's communication
      about the death). METHODS: The effects of forewarning on multiple indicators of
      mental health and grief were examined in a sample of 210 widowed persons who
      participated in the Changing Lives of Older Couples (CLOC) study. The CLOC is a
      probability sample of 1,532 married individuals aged 65 and older for whom
      baseline information was collected in 1987-88, with widowed persons reinterviewed
      6, 18, and 48 months after spousal loss. RESULTS: Forewarning did not affect
      depression, anger, shock, or overall grief 6 or 18 months after the loss.
      Prolonged forewarning was associated with elevated anxiety both 6 and 18 months
      after the death. Sudden spousal death elevated survivors' intrusive thoughts at
      the 6-month follow-up only. Sudden death was associated with slightly higher
      levels of yearning among women but significantly lower yearning among men both 6
      and 18 months after the loss. DISCUSSION: The findings call into question the
      widespread belief that grief is more severe if death is sudden and suggest a more
      complex relationship between bereavement and circumstances of spousal death.

PMID- 11445617
TI  - Social support and caregiver distress: a replication analysis.
AB  - OBJECTIVES: Prior studies have conceptualized and operationalized social support
      in different ways, making it difficult to determine if the inconsistencies in
      findings are due to differences in study design, samples, conceptualization, or
      measurement. The present study examined the replicability of models of social
      support and caregiver distress across 4 community-based caregiving studies
      representative of many conducted in the past 10 years. The goal was to identify
      areas of consistency in findings across the data sets. METHODS: The authors
      analyzed 3 models specifying patterns of relationship between social support and
      depression (main effect, mediation effect, and moderation effect) separately
      within data sets using hierarchical ordinary least squares regression. Results
      were compared across data sets. RESULTS: The replication analysis confirmed the
      robustness of behavior problems and caregiver health as important contributors to
      caregiver distress. Results of hypotheses examining the pattern of relationship
      between social support and distress were inconsistent, however. Only 1 type of
      social support was associated with distress in the expected direction: Less
      emotional support was associated with higher levels of distress in 2 of the 4
      data sets. DISCUSSION: More complex theoretical models that incorporate common
      measures to represent the linkages between types of stressor, types of support,
      and their interactions are needed to foster replicability and generalizability of
      research results.

PMID- 11445619
TI  - Lowering blood pressure in acute intracerebral hemorrhage: safe, but will it
      help?

PMID- 11445620
TI  - Do febrile seizures improve memory?

PMID- 11445621
TI  - Carbon monoxide-mediated hippocampal injury.

PMID- 11445622
TI  - Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours)
      intracerebral hemorrhage.
AB  - BACKGROUND: Arterial hypertension is common in the first 24 hours after acute
      intracerebral hemorrhage (ICH). Although increased blood pressure usually
      declines to baseline values within several days, the appropriate treatment during
      the acute period has remained controversial. Arguments against treatment of
      hypertension in patients with acute ICH are based primarily on the concern that
      reducing arterial blood pressure will reduce cerebral blood flow (CBF). The
      authors undertook this study to provide further information on the changes in
      whole-brain and periclot regional CBF that occur with pharmacologic reductions in
      mean arterial pressure (MAP) in patients with acute ICH. METHODS: Fourteen
      patients with acute supratentorial ICH 1 to 45 mL in size were studied 6 to 22
      hours after onset. CBF was measured with PET and (15)O-water. After completion of
      the first CBF measurement, patients were randomized to receive either nicardipine
      or labetalol to reduce MAP by 15%, and the CBF study was repeated. RESULTS: MAP
      was lowered by -16.7 +/- 5.4% from 143 +/- 10 to 119 +/- 11 mm Hg. There was no
      significant change in either global CBF or periclot CBF. Calculation of the 95%
      CI demonstrated that there is less than a 5% chance that global or periclot CBF
      fell by more than -2.7 mL x 100 g(-1) x min(-1). CONCLUSION: In patients with
      small- to medium-sized acute ICH, autoregulation of CBF was preserved with
      arterial blood pressure reductions in the range studied.

PMID- 11445623
TI  - Pathogenesis of cervical artery dissections: association with connective tissue
      abnormalities.
AB  - BACKGROUND: The etiology of spontaneous cervical artery dissection (CAD) is
      largely unknown. An underlying connective tissue disorder has often been
      postulated. OBJECTIVE: To further assess the association of CAD with
      ultrastructural abnormalities of the dermal connective tissue. METHODS: In a
      multicenter study, skin biopsies of 65 patients with proven nontraumatic CAD and
      10 control subjects were evaluated. The ultrastructural morphology of the dermal
      connective tissue components was assessed by transmission electron microscopy.
      RESULTS: Only three patients (5%) had clinical manifestations of skin, joint, or
      skeletal abnormalities. Ultrastructural aberrations were seen in 36 of 65
      patients (55%), consisting of the regular occurrence of composite fibrils within
      collagen bundles that in some cases resembled the aberrations found in Ehlers
      Danlos syndrome type II or III and elastic fiber abnormalities with
      minicalcifications and fragmentation. A grading scale according to the severity
      of the findings is introduced. Intraindividual variability over time was excluded
      by a second biopsy of the skin in eight patients with pronounced aberrations.
      Recurrent CAD correlated with connective tissue aberrations. In addition, similar
      connective tissue abnormalities were detected in four first-degree relatives with
      familial CAD. CONCLUSION: CAD is associated with ultrastructural connective
      tissue abnormalities, mostly without other clinical manifestations of a
      connective tissue disease. A structural defect in the extracellular matrix of the
      arterial wall leading to a genetic predisposition is suggested. The dermal
      connective tissue abnormalities detected can serve as a phenotypic marker for
      further genetic studies in patients with CAD and large families to possibly
      identify the underlying basic molecular defect(s).

PMID- 11445624
TI  - Cerebral venous thrombosis and isolated intracranial hypertension without
      papilledema in CDH.
AB  - BACKGROUND: There is evidence that patients with chronic daily headache (CDH) may
      have isolated intracranial hypertension without papilledema (IHWOP). Recent
      studies have emphasized that isolated IH may be due to cerebral venous thrombosis
      (CVT). OBJECTIVE: To detect the occurrence of CVT in patients with CDH. METHODS:
      The authors investigated the occurrence of CVT in 114 consecutive patients with
      CDH by using MR venography (MRV). A portion of these patients underwent a lumbar
      puncture (LP) to measure CSF pressure. MRV and LP were also performed in 28 age
      matched control subjects. RESULTS: In all the control subjects, both MRV and CSF
      pressure were normal. One hundred three of the 114 patients with CDH had normal
      MRV. Twenty-seven (Group 1) of these 103 patients underwent LP, and all of them
      had normal CSF pressure. Eleven (9.6%) of the 114 patients with CDH had CVT of
      one or both transverse sinuses. Six of these 11 patients had flowing
      abnormalities of one transverse sinus (Group 2), whereas the remaining five
      patients showed involvement of both transverse sinuses (Group 3). The CSF
      pressure of Group 2 was higher than that of either Group 1 or the control
      subjects, and one of the six patients showed isolated IHWOP. Patients of Group 3
      displayed the highest CSF pressure, and four of five had isolated IHWOP. The
      headache profiles of patients with CDH and CVT did not differ from those of
      patients with CDH but normal MRV. CONCLUSIONS: CVT, as detected by MRV, occurred
      in 9.6% of patients who presented with CDH. Almost half of the patients with CVT
      had isolated IHWOP. These results suggest that MRV may be a useful tool for
      selecting patients with CDH who should have LP to exclude isolated IHWOP.

PMID- 11445625
TI  - Working memory of school-aged children with a history of febrile convulsions: a
      population study.
AB  - OBJECTIVE: A prospective, population-based, case-control study was performed to
      ascertain whether febrile convulsion (FC) in early childhood is associated with
      specific working memory characteristics in school age. METHODS: From a population
      survey of 4,340 live-birth newborns in Tainan City, Taiwan, 103 children with
      confirmed FC by age 3 years were followed-up until they were at least 6 years
      old. Three analogous searching tasks dissociating the mnemonic and executive
      aspects of performances were administered to 87 of these school-aged children and
      to 87 randomly selected age-matched control subjects to assess the learning,
      spatial, and sequential working memory. RESULTS: The FC group performed
      significantly and consistently better than control subjects on all but one
      working memory measure, jumping errors. Multivariate analysis using linear
      regression revealed that the onset of FC before age 1 year was the only
      significant risk factor for deficits in mnemonic function. Prior
      neurodevelopmental delay was the only significant risk factor for deficits in
      executive function. Factors such as socioeconomic status, family predisposition
      for seizures, complex FC, recurrent FC, and subsequent unprovoked seizures were
      not risk factors for working memory deficits. CONCLUSION: The authors found that
      school-aged children with a history of FC demonstrated significantly better
      mnemonic capacity, more flexible mental processing, and higher impulsivity than
      their age-matched control subjects. The underlying mechanism for the facilitated
      working memory function in children with a history of FC needs further
      delineation.

PMID- 11445626
TI  - Cognitive deficits in children with gelastic seizures and hypothalamic hamartoma.
AB  - OBJECTIVE: To characterize the cognitive deficits in children with gelastic
      seizures and hypothalamic hamartoma and investigate the relationship of seizure
      severity to cognitive abilities. METHODS: Eight children with gelastic seizures
      and hypothalamic hamartoma completed a neuropsychological battery of standardized
      and age-normed tests, including the Woodcock-Johnson Psycho-Educational Battery
      Revised: Tests of Cognitive Ability, Peabody Picture Vocabulary Test-III, and
      initial-letter word fluency measure. RESULTS: All children displayed cognitive
      deficits, ranging from mild to severe. Gelastic/complex partial seizure severity
      was correlated with broad cognitive ability standard scores (r = -0.79; r2 =
      0.63; (F[1,6] = 10.28; p = 0.018]. Frequency of gelastic/complex partial seizures
      was also correlated with broad cognitive ability standard scores (r = -0.72; r2 =
      0.52; F[1,6] = 6.44; p = 0.044). Significant intracognitive standard score
      differences were found, with relative weaknesses in long-term retrieval (mean =
      64.1; SD = 13.3) and processing speed (mean = 67.7; SD = 21.6) and a relative
      strength in visual processing (mean = 97.6; SD = 12.8). Performance in visual
      processing differed from performance in long-term retrieval (p = 0.009) and
      processing speed (p = 0.029). CONCLUSION: These findings are consistent with
      cognitive functions and affective/emotional states associated with conduction
      pathways of the hypothalamus involving cortical association areas and amygdala
      and hippocampal formation. These abnormalities can account for the prominent
      deficit found in integrating information in the processing of memories.

PMID- 11445627
TI  - Cortical localization of reading in normal children: an fMRI language study.
AB  - BACKGROUND: fMRI provides a noninvasive means of identifying the location and
      organization of neural networks that underlie cognitive functions. OBJECTIVE: To
      identify, using fMRI, brain regions involved in processing written text in
      children. METHODS: The authors studied nine normal right-handed native English
      speaking children, aged 10.2 years (range 7.9 to 13.3 years), with two paradigms:
      reading Aesop's Fables and "Read Response Naming" (reading a description of an
      object that was then silently named). Data were acquired using blood oxygen level
      dependent fMRI. Group data were analyzed with statistical parametric mapping;
      individual data sets were analyzed with a region-of-interest approach from
      individual study t maps. The number of activated pixels was determined in brain
      regions and an asymmetry index (AI = [L - R]/[L + R]) calculated for each region.
      RESULTS: The authors found strong activation in the left middle temporal gyrus
      and left midfrontal gyrus and variable activation in left inferior frontal gyrus
      for both reading tasks in the group analysis (z > 5.5 to 9.1). All subjects had
      strong left-sided lateralization for both tasks in middle/superior temporal
      gyrus, inferior frontal gyrus, and middle frontal gyrus (AI = 0.76 to 1.0 for t =
      4). Reading Fables activated twice as many pixels in temporal cortex as the Read
      Response Naming task; activation in dorsolateral prefrontal cortex was similar
      for both tasks. Small homologous right middle temporal region activation was seen
      with reading a fable. CONCLUSIONS: The neural networks that process reading
      appear to be lateralized and localized by middle to late childhood. Reading text
      paradigms may prove useful for identifying frontal and temporal language
      processing areas and for determining language dominance in children experiencing
      epilepsy or undergoing tumor surgery.

PMID- 11445628
TI  - Effects of motor imagery on motor cortical output topography in Parkinson's
      disease.
AB  - BACKGROUND: The motor impairment in Parkinson's disease (PD) could partly reflect
      a failure to activate processes of motor imagery. OBJECTIVE: To verify any
      selective changes of motor output during motor imagery, lateralized to the
      hemisphere contralateral to the clinically affected side of hemiparkinsonian
      patients. METHODS: Transcranial magnetic stimulation (TMS) was used to map the
      cortical representations of the contralateral abductor digiti minimi muscle (ADM)
      during rest, contraction, and motor imagery in a group of patients with hemi-PD
      and in a group of healthy volunteers. Seven patients with hemi-PD and seven
      healthy subjects were examined. Focal TMS was applied over a grid of 20 scalp
      positions on each hemiscalp. Maps were characterized by area (number of excitable
      positions), volume (the sum of motor evoked potential amplitudes at all scalp
      positions), and center of gravity (a map position representing an amplitude
      weighted calculation of the excitable area). RESULTS: In healthy control
      subjects, the area of cortical representation of ADM was symmetrically increased
      in both hemispheres by mental simulation of movement and real muscle contraction.
      In patients with hemi-PD, there was a hemispheric asymmetry in the area of
      cortical representation elicited by motor imagery. The area was reduced in the
      clinically affected hemisphere. The volume of cortical representation was
      increased under all conditions and in both hemispheres in patients with PD.
      However, largely because the volume was so high at rest in patients, the
      increment in volume associated with contraction was smaller than in control
      subjects. CONCLUSION: This study demonstrates the presence of a tonic
      hyperactivation of motor cortical circuitry in PD in conjunction with an
      abnormality of either motor imagery or the process by which motor imagery engages
      the sensorimotor cortices in the clinically affected hemisphere.

PMID- 11445629
TI  - Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI
      activity in MS.
AB  - BACKGROUND: Autologous hematopoietic stem cell transplantation (ASCT) has been
      recently utilized with encouraging results in patients with poorly controlled MS.
      OBJECTIVE: To determine in severe cases of MS the effect of ASCT on gadolinium
      (Gd)-enhanced MRI and to obtain information on clinical course and safety.
      METHODS: In a cooperative study, 10 patients with rapidly evolving secondary
      progressive MS were transplanted, after BEAM conditioning regimen (carmustine,
      etoposide, cytosine-arabinoside, and melphalan), with unmanipulated autologous
      peripheral blood SC mobilized with high-dose cyclophosphamide (CY; 4 g/m2) and
      granulocyte-colony-stimulating factor. Triple-dose Gd-enhanced scans were
      performed monthly for a pretreatment period of 3 months and compared with serial
      monthly Gd-enhanced MRI for the following 6 months and then once every 3 months.
      RESULTS: The median follow-up is now 15 months (range 4 to 30 months). The number
      of Gd-enhancing lesions decreased immediately after mobilization with CY and
      finally dropped to zero in all cases after the conditioning regimen. The number
      of new T2-weighted positive lesions paralleled data obtained for Gd-enhanced MRI.
      Clinically, patients improved slightly or remained stable. CONCLUSION: These
      results demonstrate that the therapeutic sequence CY-BEAM-ASCT has the capacity
      to completely suppress MR-enhancing activity, an effect that is sustained with
      time. The final impact of this procedure on disease course remains to be
      established.

PMID- 11445630
TI  - Does adding MS-specific items to a generic measure (the SF-36) improve
      measurement?
AB  - OBJECTIVE: The 36-item Short Form Health Survey Questionnaire (SF-36) is a widely
      used generic health status measure. Recently it has been adapted to produce a
      disease-specific measure for MS-the 54-item Multiple Sclerosis Quality of Life
      Scale (MSQOL-54)-composed of five unchanged SF-36 scales; three altered SF-36
      scales (one item added to each scale); and five new scales incorporating 15
      additional items. This study evaluates the impact of these additions by comparing
      the measurement properties of the MSQOL-54 with the SF-36. METHODS: A total of
      150 patients with MS, representing a broad spectrum of disease severity,
      completed a range of questionnaires, which included the MSQOL-54 (from which the
      SF-36 score was computed). Of these, 44 people completed the measures before and
      after inpatient rehabilitation to evaluate responsiveness. Standard psychometric
      methods were used to evaluate the measurement properties. RESULTS: The
      measurement properties of the unchanged scales, inevitably, remain identical.
      Those of the three altered scales are virtually identical. Of the five new
      scales, the validity of the two sexual scales is questioned because of the high
      percentage of missing data, and the validity of the overall quality-of-life scale
      is limited as demonstrated by the low to moderate correlations with other related
      and unrelated measures. Responsiveness of the new scales also appears limited.
      CONCLUSION: Modifying existing measures by simply adding clinically chosen items
      may not be as useful as anticipated in improving the measurement properties of an
      instrument.

PMID- 11445631
TI  - Intakes of carotenoids, vitamin C, and vitamin E and MS risk among two large
      cohorts of women.
AB  - BACKGROUND: Antioxidant nutrients may reduce the risk of MS. In a recent case
      control study, vitamin C intake was significantly inversely associated with MS
      risk among women. However, no prospective data are available. OBJECTIVE: To
      examine prospectively the associations of intakes of carotenoids, vitamin C, and
      vitamin E with the risk of MS among women. METHODS: The authors documented the
      occurrence of definite and probable MS within two large cohorts of women who
      completed detailed and validated semiquantitative food frequency questionnaires.
      One cohort (Nurses' Health Study) comprised 81,683 women aged 38 to 63 years in
      1984, who were followed for 12 years; the other (Nurses' Health Study II)
      comprised 95,056 women aged 27 to 44 years in 1991, who were followed for 6
      years. RESULTS: The authors documented a total of 214 cases of MS. After
      adjustments for age, latitude of birthplace, pack-years of smoking, and total
      energy intake, the pooled multivariate relative risks (95% CIs) comparing women
      in the highest quintile with those in the lowest quintile were 1.1 (0.7 to 1.7)
      for alpha-carotene, 1.1 (0.7 to 1.6) for beta-carotene, 1.4 (0.8 to 2.2) for beta
      cryptoxanthin, 1.0 (0.6 to 1.5) for lycopene, 1.0 (0.7 to 1.6) for
      lutein/zeaxanthin, 1.4 (0.9 to 2.1) for total vitamin C, 1.3 (0.9 to 2.0) for
      dietary vitamin C, 0.8 (0.6 to 1.3) for total vitamin E, and 0.9 (0.6 to 1.4) for
      dietary vitamin E. The authors found no associations between intakes of fruits
      and vegetables and risk of MS. Use of vitamin C, vitamin E, and multivitamin
      supplements was also unrelated to risk of MS. CONCLUSIONS: These findings do not
      support hypotheses relating higher intakes of dietary carotenoids, vitamin C, and
      vitamin E to reduced risk of MS in women.

PMID- 11445632
TI  - Testosterone supplementation improves spatial and verbal memory in healthy older
      men.
AB  - OBJECTIVE: To determine the relationship between exogenous testosterone
      administration and cognitive abilities in a population of healthy older men.
      BACKGROUND: Serum levels of total and bioavailable testosterone gradually
      decrease with age in men and are associated with reductions in muscle mass,
      osteoporosis, decreased sexual activity, and changes in cognition. METHODS:
      Twenty-five healthy, community-dwelling volunteers, aged 50 to 80 years,
      completed a randomized, double-blind, placebo-controlled study. Participants
      received weekly intramuscular injections of either 100 mg testosterone enanthate
      or placebo (saline) for 6 weeks. Cognitive evaluations were conducted at
      baseline, week 3, and week 6 of treatment by use of a battery of neuropsychologic
      tests. RESULTS: Circulating total testosterone was raised an average of 130% from
      baseline at week 3 and 116% at week 6 in the treatment group. Because of
      aromatization of testosterone, estradiol increased an average of 77% at week 3
      and 73% at week 6 in the treatment group. Significant improvements in cognition
      were observed for spatial memory (recall of a walking route), spatial ability
      (block construction), and verbal memory (recall of a short story) in older men
      treated with testosterone compared with baseline and the placebo group, although
      improvements were not evident for all measures. CONCLUSIONS: The results suggest
      that short-term testosterone administration enhances cognitive function in
      healthy older men. However, it remains unclear whether these improvements in
      cognition are attributable to increased testosterone or estradiol levels, or
      both. The potential role of testosterone vs its metabolites on cognition requires
      further research.

PMID- 11445633
TI  - A gender difference in the association between APOE genotype and age-related
      cognitive decline.
AB  - OBJECTIVE: To determine whether the APOE epsilon4 allele is associated with age
      related intellectual decline in a community-dwelling sample of Danes. METHODS: A
      sample of 189 subjects who did not have dementia was tested with the Wechsler
      Adult Intelligence Scale (WAIS) at the ages of 50 and 80 years. Of these
      subjects, 163 (84 women and 79 men) completed all WAIS subtests at both
      assessments and 139 completed the digit symbol and block design subtests at the
      ages of 50, 60, 70, and 80 years. RESULTS: Cognitive decline from the age of 50
      to the age of 80 years was substantial and larger for the performance subtests
      than for the verbal subtests (the declines were 18.40 for the performance IQ and
      8.39 for the verbal IQ). APOE genotype was unrelated to the observed WAIS results
      of the 80-year assessment, but there was a significant interaction between APOE
      genotype and sex for decline scores in the performance IQ and three performance
      subtests (digit symbol, block design, and object assembly). In women, 26 epsilon4
      carriers showed larger decline than 58 noncarriers, whereas there was no
      significant relation between APOE genotype and cognitive decline in men. The
      association in women between APOE genotype and cognitive decline was significant
      only for decline in the decade from age 70 to age 80 years. The interaction
      between sex and APOE genotype remained significant when education was included as
      a covariate. CONCLUSION: The APOE epsilon4 allele is associated with normal age
      related decline in cognitive functions in women only. This finding may be
      supportive of recent evidence suggesting sex differences in APOE-associated risk
      for AD. Thus, the sex difference in the risk of sporadic AD may partly be
      explained by a sex-specific impact of the APOE epsilon4 allele on age-related
      cognitive decline.

PMID- 11445634
TI  - A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome
      8q22.1-24.1.
AB  - OBJECTIVE: To characterize a distinct form of autosomal dominant cerebellar
      ataxia (ADCA) clinically and genetically. BACKGROUND: ADCAs are a clinically,
      pathologically, and genetically heterogeneous group of neurodegenerative
      disorders. Nine responsible genes have been identified for SCA-1, -2, -3, -6, -7,
      -8, -10, and -12 and dentatorubral-pallidoluysian atrophy (DRPLA). Loci for SCA
      4, -5, -11, -13, and -14 have been mapped. METHODS: The authors studied a four
      generation Japanese family with ADCA. The 19 members were enrolled in this study.
      The authors performed the mutation analysis by PCR and a genome-wide linkage
      analysis. RESULTS: Nine members (five men and four women) were affected. The ages
      at onset ranged from 20 to 66 years. All affected members showed pure cerebellar
      ataxia, and three patients also had head tremor. Head MRI demonstrated cerebellar
      atrophy without brain stem involvement. The mutation analysis by PCR excluded
      diagnoses of SCA-1, -2, -3, -6, -7, -8, and -12 and DRPLA. The linkage analysis
      suggested linkage to a locus on chromosome 8q22.1-24.1, with the highest two
      point lod score at D8S1804 (Z = 3.06 at theta = 0.0). The flanking markers D8S270
      and D8S1720 defined a candidate region of an approximately 37.6-cM interval. This
      candidate region was different from the loci for SCA-4, -5, -10, -11, -13, and 
      14. CONCLUSION: The family studied had a genetically novel type of SCA (SCA-16).

PMID- 11445635
TI  - A somatic and germline mosaic mutation in MPZ/P(0) mimics recessive inheritance
      of CMT1B.
AB  - OBJECTIVE: To identify the molecular basis of a demyelinating Charcot-Marie-Tooth
      disease type 1 (CMT1) with presumed autosomal recessive inheritance. BACKGROUND:
      CMT1, an inherited motor and sensory neuropathy with low nerve conduction
      velocities, is caused by dominantly inherited mutations in the genes of the
      peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ/P(0)), and early
      growth response 2 transcription factor (EGR2/Krox-20). PATIENTS AND METHODS: Two
      young sisters born of clinically and electrophysiologically healthy parents had a
      severe CMT1 neuropathy of presumed autosomal recessive inheritance. The older
      sister underwent a nerve biopsy. The authors analyzed PMP22, MPZ/P(0), and
      EGR2/Krox-20 by automated direct nucleotide sequencing. For rapid mutation
      detection, they determined the restriction-fragment-length polymorphisms for TaqI
      in the fluorescein-labeled target DNA sequence amplified by PCR. RESULTS: Nerve
      biopsy disclosed a demyelinating and remyelinating neuropathy with onion bulb
      formations. Both sisters had a novel heterozygous G308-->A transition of MPZ/P(0)
      without any mutation of PMP22 or EGR2/Krox-20. The G308-->A transition was a
      nonconservative mutation that changed a glycine into a glutamate at the amino
      acid residue 74 in the extracellular domain of the mature MPZ/P(0). None of 50
      healthy controls had the mutation. The healthy mother had a low amount of the
      mutation in blood (congruent with 20%) as well as in skin, buccal epithelium, and
      hairs (30%). Because the healthy mother carried clones of somatic mutant cells
      and had transmitted the G308-->A transition to the affected daughters, she also
      harbored germline mutant cells. CONCLUSION: In hereditary demyelinating
      neuropathies, somatic and germline mosaicism of dominant mutations in the myelin
      protein genes may mimic autosomal recessive inheritance.

PMID- 11445636
TI  - Hereditary benign chorea: clinical and genetic features of a distinct disease.
AB  - OBJECTIVE: To describe a second family with benign hereditary chorea (BCH, OMIM
      118700) and suggestive linkage to chromosome 14q. BCH is an autosomal dominant
      disorder of early onset that differs from Huntington disease in being
      nondementing and nonprogressive without other neurologic signs. There has been
      controversy regarding the existence of BCH as a discrete disorder. BACKGROUND: A
      single kindred was recently reported with linkage of BCH to a 20.6-KcM region on
      chromosome 14q. METHODS: In a four-generation family with BCH, linkage was
      evaluated to markers in a 23-KcM region between D14S49 and D14S66 that contains
      the putative BCH locus. RESULTS: A multipoint nonparametric lod score of 3.01 is
      consistent with linkage of disease in this family to the 14q BCH locus. A
      recombination event in one affected individual enabled the critical region to be
      narrowed to 6.93 KcM flanked by D14S1068 and D14S1064. This region contains two
      candidate genes: glial maturation factor beta and guanosine triphosphate
      cyclohydrolase 1 (GCH1). Survival motor neuron (SMN) interacting protein-1 is
      eliminated as a candidate gene because it lies outside the critical region. No
      sequence alteration was identified in the coding region of GCH1 in an affected
      individual. CONCLUSION: These data provide further evidence that BCH is a
      distinct entity, narrow the location of BCH to a 6.93-KcM region on chromosome
      14q, and exclude SMN interacting protein-1 as a candidate gene.

PMID- 11445637
TI  - Evidence for familial aggregation of tremor in normal individuals.
AB  - BACKGROUND: Tremor occurs in most normal individuals, and this tremor may offer
      basic clues about the mechanisms of neuromuscular control. It is not known
      whether genetic factors influence the magnitude of tremor in normal families.
      OBJECTIVE: To assess the familial aggregation of tremor in normal families.
      METHODS: Control subjects from the Washington Heights-Inwood community in
      northern Manhattan, NY, were enrolled in a family study. These subjects and their
      first- and second-degree relatives underwent a videotaped tremor examination. Two
      neurologists rated the severity of tremor on the videotaped examination,
      assigning a total tremor score (0 to 36 [maximum]). Associations between the
      control subjects' and their relatives' total tremor scores were assessed using
      correlation coefficients and linear regression analysis. In addition, maximum
      likelihood methods were used to fit a linear mixed-effects model to the total
      tremor scores of probands and their siblings, after excluding any relatives with
      essential tremor. RESULTS: There were 56 control subjects and 226 relatives.
      Tremor was clinically detectable in 221 (97.8%) of 226 relatives. There was an
      association between the control subjects' total tremor scores and those of their
      siblings (r = 0.40; p = 0.018), those of all of their first-degree relatives
      (siblings and children combined, r = 0.20; p = 0.037), but not those of their
      second-degree relatives (r = 0.002; p = 0.99). In analyses of probands and normal
      siblings, the estimate of the variance of the family-specific component of the
      age-adjusted total tremor score was different from zero (p < 0.005), and the
      family specific component was estimated to account for 52% of the variability in
      the scores. CONCLUSIONS: Tremor aggregates in normal families, suggesting that
      genetic factors may contribute to its etiology. Other studies might be designed
      by investigators to identify these genes through genetic linkage or association
      analysis. Identification of such genes would help to elucidate the mechanisms
      underlying this ubiquitous condition.

PMID- 11445638
TI  - Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular
      dystrophy.
AB  - BACKGROUND: Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal
      recessive disorder characterized by severe dystrophic muscle wasting from birth
      or early infancy with structural brain abnormalities. The gene for FCMD is
      located on chromosome 9q31, and encodes a novel protein named fukutin. The
      function of fukutin is not known yet, but is suggested to be an enzyme that
      modifies the cell-surface glycoprotein or glycolipids. OBJECTIVE: To elucidate
      the roles of fukutin gene mutation in skeletal and cardiac muscles and brain.
      METHODS: Immunohistochemical and immunoblot analyses were performed in skeletal
      and cardiac muscles and brain tissue samples from patients with FCMD and control
      subjects. RESULTS: The authors found a selective deficiency of highly
      glycosylated alpha-dystroglycan, but not beta-dystroglycan, on the surface
      membrane of skeletal and cardiac muscle fibers in patients with FCMD. Immunoblot
      analyses also showed no immunoreactive band for alpha-dystroglycan, but were
      positive for beta-dystroglycan in FCMD in skeletal and cardiac muscles.
      CONCLUSION: The current findings suggest a critical role for fukutin gene
      mutation in the loss or modification of glycosylation of the extracellular
      peripheral membrane protein, alpha-dystroglycan, which may cause a crucial
      disruption of the transmembranous molecular linkage of muscle fibers in patients
      with FCMD.

PMID- 11445639
TI  - Early left periventricular brain lesions induce right hemispheric organization of
      speech.
AB  - Right-hemispheric organization of speech has been observed following early left
      sided brain lesions involving the language cortex. The authors studied speech
      organization in hemiparetic patients with pre- and perinatally acquired lesions
      in the left periventricular white matter using fMRI, and found that right
      hemisphere activation correlated with left facial motor tract involvement. This
      suggests that the impairment of speech motor output from the left hemisphere
      plays an important role in this alteration of language representation.

PMID- 11445640
TI  - Seizures accelerate forgetting in patients with left-sided temporal lobe
      epilepsy.
AB  - Ten patients with refractory temporal lobe epilepsy performed a word-position
      association learning task every 24 hours during video EEG monitoring. On 55
      occasions recall performance was tested 30 minutes and 24 hours after the initial
      learning phase. Patients with left- but not right-sided temporal lobe epilepsy
      exhibited impaired retention of word position if a seizure had occurred during
      the preceding 24-hour interval. Seizures may impair the consolidation of memory
      in patients with left-sided temporal lobe epilepsy beyond the chronic memory
      deficits caused by the underlying pathology.

PMID- 11445641
TI  - Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of
      fragile X.
AB  - The authors report five elderly men with the fragile X premutation who had a
      progressive action tremor associated with executive function deficits and
      generalized brain atrophy. These individuals had elevated fragile X mental
      retardation 1 gene (FMR1) messenger RNA and normal or borderline levels of FMR1
      protein. The authors propose that elevations of FMR1 messenger RNA may be
      causative for a neurodegenerative syndrome in a subgroup of elderly men with the
      FMR1 premutation.

PMID- 11445642
TI  - Headache characteristics in patients after migrainous stroke.
AB  - Six patients who fulfilled strictly defined criteria for migrainous cerebral
      infarction and in whom other causes of stroke were ruled out were observed. All
      had a long-standing history of migraine with aura. In most, stroke was mild with
      good recovery and no recurrence. Headache frequency and severity decreased after
      the stroke. It is hypothesized that the improvement in migraine may be due to
      reduced nociceptive transmission as result of loss in vasoreactivity of the
      affected cerebral blood vessel.

PMID- 11445643
TI  - Levels of nerve growth factor in cerebrospinal fluid of chronic daily headache
      patients.
AB  - Nerve growth factor (NGF) levels were determined in the CSF of patients with
      chronic daily headache (CDH) and correlated with levels of sensory neuropeptides.
      Patients with CDH showed higher NGF levels in the CSF compared with control
      subjects (p < 0.0001). Higher CSF levels of substance P (SP) (p < 0.002) and
      calcitonin-gene-related peptide (CGRP) (p < 0.0001) were also found. There was a
      significant positive correlation between NGF and both SP and CGRP values. These
      findings suggest that NGF is involved in the long-lasting sensitization and
      sustained activation of the trigeminal system in CDH.

PMID- 11445644
TI  - Recurrent subarachnoid hemorrhage associated with a new transthyretin variant
      (Gly53Glu).
AB  - CNS involvement is rare in systemic amyloidoses due to transthyretin (TTR)
      mutation and manifests as a combination of dementia, seizures, and myelopathy.
      The authors report two French siblings who experienced recurrent subarachnoid
      hemorrhages as the main clinical feature. Brain specimens showed that the
      leptomeningeal vessels walls were thickened by amyloid deposits, and sequencing
      of the TTR exons showed a heterozygous single base-pair transition from G to A
      (codon 53), resulting in a glycine for glutamic acid substitution (G53E).

PMID- 11445645
TI  - Tau genotype: no effect on onset, symptom severity, or survival in progressive
      supranuclear palsy.
AB  - Genetic studies have shown that progressive supranuclear palsy (PSP) is
      associated with inheritance of a specific genotype (H1/H1) in the tau gene. The
      authors investigated whether the H1/H1 genotype or A0/A0 genotype independently
      or in conjunction with selected environmental risk factors influences the age at
      onset, severity, or survival in patients with PSP. Our findings suggest that tau
      genotyping does not predict the prognosis of PSP.

PMID- 11445646
TI  - A 13-year-old boy with cognitive impairment, retinoblastoma, and Wilson disease.
AB  - A developmentally delayed child manifested retinoblastoma at age 4 years and
      Wilson disease at age 11, a previously unreported association. Cytogenetic and
      molecular analysis showed an interstitial deletion in the long arm of the
      paternally derived homologue of chromosome 13 (13q14.2-13q22.2), which
      encompasses the retinoblastoma and Wilson disease loci. The authors postulate
      that the co-occurrence of retinoblastoma and Wilson disease was the consequence
      of an acquired somatic mutation at the retinoblastoma locus and an inherited
      mutation at the Wilson disease locus of the maternally derived chromosome 13,
      superimposed on the hemizygosity associated with the paternally derived deletion.

PMID- 11445647
TI  - Effects of bilateral subthalamic nucleus stimulation on parkinsonian gait.
AB  - Gait analysis was carried out to assess the effects of L-dopa and bilateral
      subthalamic nucleus stimulation on gait velocity, cadence, stride length, and
      gait kinematics in nine patients with PD. Substantial effects of bilateral
      subthalamic nucleus stimulation on gait, with an increase in gait velocity and
      stride length comparable to that of a suprathreshold L-dopa dose, were found.
      Interestingly, stride length was more improved by L-dopa and cadence more by
      subthalamic nucleus stimulation. In two patients with freezing during the "on"
      period, subthalamic nucleus stimulation failed to reduce this symptom
      effectively.

PMID- 11445648
TI  - Extinction, working memory, and line bisection in spatial neglect.
AB  - The authors studied four patients with spatial neglect, using a task in which
      lines contain an off-centered bisection mark and a task in which the right and
      left segments of these bisected lines are presented independently and
      sequentially. In the prebisected line task, subjects reported the position of the
      bisection. In the segments task, subjects compared the length of the segments.
      Accuracy was greater with the sequential presentation of line segments,
      suggesting that an extinction-like phenomenon plays a role in line bisection
      bias.

PMID- 11445649
TI  - Myopathy with tubulin-reactive crystalline inclusions.
AB  - A 61-year-old man with muscle aches and persistently elevated serum creatine
      kinase had aggregates of randomly oriented, rhomboidal or rectangular protein
      crystalline inclusions in the sarcoplasm of type II fibers. Immunochemical
      studies showed strong reactivity of the inclusions to tubulin antibodies,
      suggesting that these unique crystalline inclusions may be a consequence of
      altered synthesis, processing, or degradation of tubulin.

PMID- 11445650
TI  - A prospective study of quality of life in ALS patients treated with noninvasive
      ventilation.
AB  - Noninvasive positive pressure ventilation prolongs survival in ALS but its effect
      on quality of life is unknown. The authors prospectively studied quality of life
      using the SF-36 questionnaire in a cohort of 16 ventilated patients with ALS.
      Noninvasive positive pressure ventilation improved scores in the "Vitality"
      domain by as much as 25%, for periods of up to 15 months, despite disease
      progression. Noninvasive positive pressure ventilation did not cause reduced
      quality of life, as any fall in scores in the ventilated group were comparable to
      those seen in a control group. In conclusion, noninvasive positive pressure
      ventilation enhances quality of life when used to treat sleep-disordered
      breathing in patients with ALS.

PMID- 11445651
TI  - Successful use of rt-PA in pediatric stroke.

PMID- 11445652
TI  - The HLA-DR13 haplotype is associated with "benign" multiple sclerosis in
      northeast Italy.

PMID- 11445653
TI  - Serum transferrin receptor levels in Friedreich's and other degenerative ataxias.

PMID- 11445654
TI  - Recurrent ischemia in symptomatic carotid occlusion: prognostic value of
      hemodynamic factors.

PMID- 11445655
TI  - Localization of the "sneeze center".

PMID- 11445656
TI  - Valproic acid toxicity mimicking multiple system atrophy.

PMID- 11445657
TI  - Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood
      vessels.

PMID- 11445658
TI  - Cognitive tests that best discriminate between presymptomatic AD and those who
      remain nondemented.

PMID- 11445659
TI  - Larger amounts of visceral adipose tissue in Asian Americans.
AB  - OBJECTIVE: Excess visceral adipose tissue (VAT) is recognized as an important
      risk factor for the development of coronary heart disease and type 2 diabetes.
      Several studies have reported less VAT in African Americans compared with whites.
      As little is known about the levels of VAT in Asians, we compared whole-body VAT
      in Asian Americans with European Americans. RESEARCH METHODS AND PROCEDURES: VAT
      was measured using whole-body multislice magnetic resonance imaging in 54 women
      (18 Asian Americans, 36 European Americans) and 53 men (19 Asian Americans, 34
      European Americans) with body mass index (measured in kilograms per square meter)
      < 30. Data were analyzed by multiple regression modeling. RESULTS: Asian American
      women had higher log-transformed VAT compared with European American women (p <
      0.05), after adjusting for age and total body fat. There was a significant age by
      race interaction such that race differences in VAT were most evident over the age
      of 30 years. No differences in VAT could be detected between Asian American and
      European American men, even after adjusting for potential covariates, including
      total adiposity. DISCUSSION: These data are the first to demonstrate higher
      amounts of VAT in healthy Asian Americans, a finding that suggests normative VAT
      values or standards derived from whites may not be applicable to Asians.

PMID- 11445660
TI  - The expression of SPARC in adipose tissue and its increased plasma concentration
      in patients with coronary artery disease.
AB  - OBJECTIVE: Adipocytes secrete various cytokines and matrix proteins. Several of
      them precipitate in obesity-associated diseases, including atherosclerosis. In
      the current study, we have examined the expression of secreted protein, acidic
      and rich in cysteine (SPARC) in adipose tissue and its significance in obesity
      and coronary artery disease (CAD). RESEARCH METHODS AND PROCEDURES: The SPARC
      mRNA expressions both in vivo and in vitro were detected by Northern blot
      analysis. Plasma SPARC concentrations were measured by enzyme immunosorbent
      assay. First, we investigated the plasma SPARC levels of 88 unrelated adult
      Japanese subjects (62 men and 26 women; average age: [+/- SD] 50 +/- 12 years;
      body mass index [BMI]: 16 to 46 kg/m(2)). Additionally 31 subjects with CAD
      diagnosed by coronary angiography (20 men and 11 women) were also investigated.
      RESULTS: Human adipose tissues expressed abundant SPARC mRNA. SPARC expression in
      adipose tissues was upregulated in obese db/db mice. Markedly enhanced expression
      of SPARC mRNA was observed in 3T3-L1 fibroblasts during adipocyte
      differentiation. Consistent with these results, plasma SPARC levels proved a
      positive correlation with BMI in humans (r = 0.27; p < 0.01). Interestingly,
      plasma SPARC concentrations were significantly elevated in age- and BMI-matched
      subjects with CAD (p < 0.05). DISCUSSION: SPARC was expressed in adipose tissues
      and its expression was enhanced in obese mice. In human, plasma SPARC levels were
      elevated in obesity and CAD patients. This elevated SPARC may be involved in the
      progression of CAD.

PMID- 11445661
TI  - Stability of adiposity phenotypes from childhood and adolescence into young
      adulthood with contribution of parental measures.
AB  - OBJECTIVE: The stability of several indicators of body composition and adipose
      tissue distribution over 12 years was quantified. RESEARCH METHODS AND
      PROCEDURES: The participants were 77 boys and 76 girls who were evaluated along
      with their parents at baseline as children and adolescents (8 to 18 years of age)
      and remeasured as young adults 12 years later. Indicators of body composition
      included the body mass index, fat mass, fat free mass, percentage of body fat,
      sum of six skinfolds (SF6), and the first principal component of six age-adjusted
      skinfold residuals. Relative adipose tissue distribution was represented by the
      second principal component of skinfold residuals and a trunk-to-extremity
      skinfold ratio, adjusted for SF6. RESULTS: Partial interage correlations,
      controlling for initial age and length of follow-up, were 0.65 and 0.59 for the
      body mass index, 0.59 and 0.64 for fat mass, 0.65 and 0.57 for fat free mass,
      0.50 and 0.57 for percentage of body fat, 0.66 and 0.44 for SF6, 0.64 and 0.42
      for the first principal component of six age-adjusted skinfold residuals, 0.19
      and 0.31 for the second principal component of skinfold residuals, and 0.41 and
      0.47 for trunk-to-extremity skinfold ratio, adjusted for SF6, in men and women,
      respectively. Multiple regression analyses indicated that the significant partial
      R(2) values of parental measurements on the prediction of their offspring in
      young adulthood ranged from 2% to 9%. DISCUSSION: The results indicate moderately
      high stability of indicators of body composition and somewhat lower stability of
      measures of adipose tissue distribution. Overall, parental measures offer less
      predictive value than do measures of childhood and adolescent body composition
      and adipose tissue distribution.

PMID- 11445662
TI  - Intracerebroventricular glucocorticoid infusion in normal rats: induction of
      parasympathetic-mediated obesity and insulin resistance.
AB  - OBJECTIVE: The aims of the present study were to determine whether increased body
      weight resulting from intracerebroventricular (ICV) glucocorticoid
      (dexamethasone) infusion in normal rats is associated, as in obesity, with
      changes in glucose metabolism and to investigate whether the parasympathetic
      nervous system is involved in the glucocorticoid-induced effects. RESEARCH
      METHODS AND PROCEDURES: Male Sprague-Dawley rats were infused with ICV
      dexamethasone (2.5 microg/d) or its vehicle for 2 days during which food intake,
      body weight, and basal insulinemia were measured. Euglycemic-hyperinsulinemic
      clamps associated with the labeled 2-deoxyglucose technique were then performed
      to determine the total rate of glucose disappearance and the tissue glucose use
      indices. Similar experiments were carried out in vagotomized rats. RESULTS: Two
      days of ICV glucocorticoid infusion in normal rats resulted in increases in food
      intake, body weight, basal insulinemia, and produced decreases in the insulin
      stimulated total rate of glucose disappearance, as well as in glucose use indices
      of all muscle types studied. None of these alterations was observed when
      glucocorticoid infusion was carried out in vagotomized rats. DISCUSSION: These
      data show that central glucocorticoid infusion favors anabolic processes, such as
      feeding behavior, body weight gain, and insulin output, while promoting muscle
      insulin resistance. These effects seem to be mediated by an activation of the
      parasympathetic nervous system, because they all disappear when tested in
      vagotomized rats.

PMID- 11445663
TI  - Opioidergic modulation of ventilatory response to sustained hypoxia in obese
      Zucker rats.
AB  - OBJECTIVE: To determine whether altered central and/or peripheral opioidergic
      mechanisms contribute to the altered ventilatory response to sustained hypoxia in
      obese Zucker rats. RESEARCH METHODS AND PROCEDURES: Eight lean (176 +/- 8 [SEM]
      g) and eight obese (225 +/- 12 g) Zucker rats were studied at 6 weeks of age.
      Pulmonary ventilation ((E)), tidal volume (V(T)), and breathing frequency (f) at
      rest and in response to sustained (30 minutes) hypoxic (10% O(2)) challenges were
      measured on three separate occasions by the barometric method after the
      randomized, blinded administration of equal volumes of saline (control), naloxone
      methiodide (N(M); 5 mg/kg, peripheral opioid antagonist), or naloxone
      hydrochloride (N(HCl); 5 mg/kg, peripheral and central opioid antagonist).
      RESULTS: Administration of N(M) and N(HCl) in lean animals had no effect on (E)
      either at rest or during 30 minutes of sustained exposure to hypoxia. Similarly,
      N(M) failed to alter (E) in obese rats. In contrast, N(HCl) significantly (p <
      0.05) increased (E) and V(T) both at rest and during 2 to 10 minutes of hypoxic
      exposure in obese rats. After 20 to 30 minutes of hypoxic exposure, V(T) remained
      elevated with N(HCl), but the earlier elevation of (E) seemed to be attenuated
      due to a decrease in f at 20 minutes of exposure to hypoxia. DISCUSSION: Thus,
      endogenous opioids modulate both resting (E) and the ventilatory response to
      sustained hypoxia in obese, but not in lean, Zucker rats by acting specifically
      on opioid receptors located within the central nervous system.

PMID- 11445664
TI  - Circulating interleukin-6 in relation to adiposity, insulin action, and insulin
      secretion.
AB  - OBJECTIVE: Plasma concentrations of interleukin-6 (IL-6), a proinflammatory
      cytokine produced and released in part by adipose tissue, are elevated in people
      with obesity and type 2 diabetes. Because recent studies suggest that markers of
      inflammation predict the development of type 2 diabetes, we examined whether
      circulating plasma IL-6 concentrations were related to direct measures of insulin
      resistance and insulin secretory dysfunction in Pima Indians, a population with
      high rates of obesity and type 2 diabetes. RESEARCH METHODS AND PROCEDURES:
      Fasting plasma IL-6 concentrations (enzyme-linked immunosorbent assay), body
      composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and
      acute insulin secretory responses to glucose (25 g intravenous glucose tolerance
      test) were measured in 58 Pima Indians without diabetes (24 women, 34 men).
      RESULTS: Fasting plasma IL-6 concentrations were positively correlated with
      percentage of body fat (r = 0.26, p = 0.049) and negatively correlated with M (r
      = -0.28, p = 0.031), but were not related to acute insulin response (r = 0.13, p
      = 0.339). After adjusting for percentage of body fat, plasma IL-6 was not related
      to M (partial r = -0.23, p = 0.089). DISCUSSION: Fasting plasma IL-6
      concentrations are positively related to adiposity and negatively related to
      insulin action in Pima Indians. The relationship between IL-6 and insulin action
      seems to be mediated through adiposity.

PMID- 11445665
TI  - Different methods for assessing the features of eating disorders in patients with
      binge eating disorder: a replication.
AB  - OBJECTIVE: To compare different methods for assessing the features of eating
      disorders in patients with binge eating disorder (BED). RESEARCH METHODS AND
      PROCEDURES: A total of 47 participants with BED were administered the Eating
      Disorder Examination (EDE) Interview and completed the EDE-Questionnaire (EDE-Q)
      at baseline. A total of 37 participants prospectively self-monitored their eating
      behaviors daily for 4 weeks and then completed another EDE-Q. RESULTS: At
      baseline, the EDE and the EDE-Q were significantly correlated on frequencies of
      objective bulimic episodes (binge eating), overeating episodes, and on the
      dietary restraint, eating concern, weight concern, and shape concern subscales.
      Mean differences in the EDE and EDE-Q frequencies of objective bulimic episodes
      and overeating were not significant but scores on the four subscales differed
      significantly, with the EDE-Q yielding higher scores. At the 4-week point, the
      EDE-Q retrospective 28-day assessment was significantly correlated with the
      prospective daily self-monitoring records for frequency of objective bulimic
      episodes and the mean difference between the methods was not significant. The EDE
      Q and self-monitoring findings for subjective bulimic episodes and objective
      overeating differed significantly. DISCUSSION: In patients with BED, the three
      assessment methods showed some areas of acceptable convergence.

PMID- 11445666
TI  - The role of apoptosis in regulating hematopoietic stem cell numbers.
AB  - The importance of apoptosis, in combination with proliferation, in maintaining
      stable populations has become increasingly clear in the last decade. Perturbation
      of either of these processes can have serious consequences, and result in a
      variety of disorders. Moreover, as the players and pathways gradually emerge, it
      turns out that there are strong connections in the regulation of cell cycle
      progression and apoptosis. Apoptosis, proliferation, and the disorders resulting
      from aberrant regulation have been studied in a variety of cell types and
      systems. Hematopoietic stem cells (HSC) are defined as primitive mesenchymal
      cells that are capable of both self-renewal and differentiation into the various
      cell lineages that constitute the functioning hematopoietic system. Many (but
      certainly not all) mature hematopoietic cells are relatively short-lived,
      sometimes with a half-life in the order of days. Homeostasis requires the
      production of 10(8) (mouse) to 10(11) (human) cells each day. All of these cells
      are ultimately derived from HSC that mostly reside in the bone marrow in adult
      mammals. The study of the regulation of HSC numbers has focussed mainly on the
      choice between self-renewal and differentiation, symmetric and asymmetric cell
      divisions. Recently, however, it has been directly demonstrated that apoptosis
      plays an important role in the regulation of hematopoietic stem cells in vivo.

PMID- 11445667
TI  - XIAP: apoptotic brake and promising therapeutic target.
AB  - The X-linked Inhibitor of Apoptosis, XIAP, is a key member of the newly
      discovered family of intrinsic inhibitors of apoptosis (IAP) proteins. IAPs block
      cell death both in vitro and in vivo by virtue of inhibition of distinct
      caspases. Although other proteins have been identified which inhibit upstream
      caspases, only the IAPs have been demonstrated to be endogenous repressors of the
      terminal caspase cascade. In turn, the caspase inhibiting activity of XIAP is
      negatively regulated by at least two XIAP-interacting proteins, XAF1 and
      Smac/DIABLO. In addition to the inhibition of caspases, recent discoveries from
      several laboratories suggest that XIAP is also involved in a number of other
      biologically significant cellular activities including modulation of receptor
      mediated signal transduction and protein ubiquitination. XIAP is also translated
      by a rare cap-independent mechanism mediated by a specific sequence called IRES
      (for Internal Ribosome Entry Site) which is found in the XIAP 5(') UTR. XIAP
      protein is thus synthesized under various conditions of cellular stress such as
      serum starvation and low dose gamma-irradiation induced apoptosis, conditions
      that lead to the inhibition of cellular protein synthesis. The multiple
      biological activities of XIAP, its unique translational and post-translational
      control and the centrality of the caspase cascade make the control of XIAP
      expression an exceptionally promising molecular target for modulating apoptosis.
      Therapeutic benefits can be derived from both the suppression of inappropriate
      cell death such as in neurodegenerative disorders and ischemic injury or in the
      activation of latent cell death pathways such as in autoimmune disease and cancer
      where apoptosis induction is the desired outcome.

PMID- 11445668
TI  - Phosphatidylserine induces apoptosis in adherent cells.
AB  - Phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane in
      apoptotic cell death. However, the roles of PS in apoptotic signaling are still
      unclear. In this study, we found that exogenous PS, but not other phospholipids,
      induced cell death in adherent cells, but not in suspension culture. The cell
      death exhibited typical features of apoptosis such as cell shrinkage, nuclear
      fragmentation and abnormal chromatin condensation. When PS was added to CHO-K1
      cells in monolayer culture, they began to show changes in cell shape and actin
      cytoskeleton and protein kinase C (PKC) activity, followed by cell detachment,
      caspase activation, cleavage of focal adhesion kinase (FAK) and finally loss of
      viability. These results suggested that PS causes apoptosis through actin
      disorganization, cell detachment and cleavage of FAK.

PMID- 11445669
TI  - Quantitative determination of apoptosis on leukemia cells by infrared
      spectroscopy.
AB  - Quantitation of apoptotic cell death in vivo has become an important issue for
      patients with acute leukemia. We describe herein a new analytical method, based
      on infrared (IR) spectroscopy, to estimate the percentage of apoptotic leukemic
      cells in two different cell lines (CEM and K562), induced with etoposide (VP-16).
      As the percentage of apoptosis increases, the protein structure shifts from
      dominantly beta-sheet to unordered (random coil), the overall lipid content
      increases and the amount of detectable DNA decreases. These changes can be
      directly related to the percentage of apoptosis as determined by two standard
      reference methods: flow cytometry and DNA ladder formation. The correlation
      between the significant IR spectral changes and the percentage of apoptotic
      leukemia cells in the two cell lines was optimal up to 24 h following etoposide
      treatment (r = 0.99 for CEM cells and r = 0.96 for K562 cells). Furthermore, IR
      spectroscopy is able to detect apoptotic changes in these cells already after 4 h
      treatment with VP-16, compared to flow cytometry which needs 6 h to observe
      significant changes. Our study suggests that IR spectroscopy may have potential
      clinical utility for the early, fast and reagent free assessment of
      chemotherapeutic efficacy in patients with leukemia.

PMID- 11445670
TI  - Progressively developed myocardial apoptotic cell death during late phase of
      reperfusion.
AB  - Myocardial apoptosis is primarily triggered during reperfusion (R). The aim of
      this study was to test the hypothesis that R-induced apoptosis develops
      progressively during the late phase of R, and that R-induced apoptosis is
      associated with changes in expression of anti- and pro-apoptotic proteins and
      infiltrated inflammatory cells. Thirty-one dogs were subjected to 60 min of left
      anterior descending coronary occlusion followed by 6, 24, 48, and 72 h R,
      respectively. There was no group difference in collateral blood flow, measured by
      colored microspheres during ischemia. Necrotic cell death (TTC staining) was
      significantly increased during R, starting at 27 +/- 2% at 6 h R and increasing
      to 41 +/- 2% at 24 h R. There was no further change at 48 (37 +/- 3%) and 72 (36
      +/- 6%) h R, respectively. TUNEL positive cells (% total normal nuclei) in the
      peri-necrotic zone progressively increased from 6 (26 +/- 2) to 24 (38 +/- 1), 48
      (48 +/- 3) and 72 (59 +/- 4) h R, respectively. The number of detected TUNEL
      positive cells at these time points was consistent with an increased intensity of
      DNA ladders, identified by agarose gel electrophoresis. Compared with normal
      tissue, western blot analysis showed persistent reduction in expression of anti
      apoptotic protein Bcl-2 from 6 (16 +/- 0.8%) to 72 h R (78 +/- 2%), and increase
      in expression of pro-apoptotic proteins including Bax from 6 (30 +/- 3%) to 72 h
      R (66 +/- 3%), and p53 from 6 (12 +/- 1%) to 72 h R (91 +/- 2%), respectively.
      Immunohistochemical staining revealed that infiltrated neutrophils (mm(2)
      myocardium) were significantly correlated with development of necrotic and
      apoptotic cell death from 6 to 24 h R, respectively (P < 0.05), while large
      macrophage infiltration seen during 48 to 72 h R were correlated with apoptotic
      cell death (P < 0.05). These results indicate that 1) necrosis peaked at 24 h R
      when apoptosis was still progressively developing during later R; 2) changes in
      Bcl-2 family and p53 proteins may participate in R-induced myocardial apoptosis;
      3) inflammatory cells may play a role in triggering cell death during R. P < 0.05
      vs. normal nuclei and tissue; P < 0.01 vs. 6 h R.

PMID- 11445671
TI  - BAPTA blocks DNA fragmentation and chromatin condensation downstream of caspase-3
      and DFF activation in HT-induced apoptosis in HL-60 cells.
AB  - DFF ((DNA Fragmentation Factor) is a heterodimer composed of 40 kDa (DFF40, CAD)
      and 45 kDa (DFF45, ICAD) subunits. During apoptosis, activated caspase-3 cleaves
      DFF45 and activates DFF40, a DNase that targets nucleosomal linker region and
      cleaves chromatin DNA into nucleosomal fragments. We have previously reported
      that HT induced apoptosis in HL-60 cells, and intracellular Ca(2+) chelator BAPTA
      blocked apoptosis-associated DNA fragmentation induced by HT. We report here that
      HT also induced activation of caspase-3 and cleavage of DFF45. BAPTA prevented
      neither the caspase-3 activation nor the cleavage of DFF45. Mitochondrial
      membrane potential was disrupted in BAPTA-AM treated cells. However, BAPTA did
      prevent DNA fragmentation and chromatin condensation in HT-treated cells. These
      data suggest a novel role for intracellular calcium in regulating apoptotic
      nuclease that causes DNA fragmentation and chromatin condensation.

PMID- 11445672
TI  - The analysis of cThy28 expression in avian lymphocytes.
AB  - During the course of a screening procedure designed to isolate gene products that
      mediate avian lymphocyte apoptosis, a 1070 bp cDNA encoding a 242 amino acid
      protein, cThy28 (GenBank accession number U34350), was isolated. Based on the
      deduced amino acid sequence, cThy28 is a conserved protein that shares greater
      than 90% amino acid similarity with several putative mammalian homologues. A
      structural analysis of the protein suggests that is a nuclear-localized,
      phosphoprotein with potential glycosylation and myristolation sites. Compared to
      other non-lymphoid tissues, the cThy28 protein and its transcript are present in
      immune organs at elevated levels. When the expression of cThy28 was analyzed in
      cultured bursal lymphocytes undergoing apoptosis, the cellular levels of this
      protein and its transcript declined and underwent degradative processes as a
      function of the apoptotic process. Treatment of lymphocytes with phorbol esters
      inhibited apoptosis and protected the cellular levels of the cThy28 protein and
      its transcript from undergoing this degradative process; however, analysis of
      transcripts of a "housekeeping" gene, GAPDH (glyceraldehyde phosphate
      dehydrogenase), revealed a similar response to this apoptosis treatment regimen.
      Thus, the apoptotic-mediated alterations in cThy28 expression and its role in
      lymphocyte function remain undefined; however, the potential task of this gene in
      apoptosis may be related to the putative functions of the cThy28 mammalian
      homologues identified in this report.

PMID- 11445673
TI  - Critical care at the tipping point: the presidential address from the 30th
      Educational and Scientific Symposium of the Society of Critical Care Medicine.

PMID- 11445675
TI  - Epidemiology of severe sepsis in the United States: analysis of incidence,
      outcome, and associated costs of care.
AB  - OBJECTIVE: To determine the incidence, cost, and outcome of severe sepsis in the
      United States. DESIGN: Observational cohort study. SETTING: All nonfederal
      hospitals (n = 847) in seven U.S. states. PATIENTS: All patients (n = 192,980)
      meeting criteria for severe sepsis based on the International Classification of
      Diseases, Ninth Revision, Clinical Modification. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We linked all 1995 state hospital discharge
      records (n = 6,621,559) from seven large states with population and hospital data
      from the U.S. Census, the Centers for Disease Control, the Health Care Financing
      Administration, and the American Hospital Association. We defined severe sepsis
      as documented infection and acute organ dysfunction using criteria based on the
      International Classification of Diseases, Ninth Revision, Clinical Modification.
      We validated these criteria against prospective clinical and physiologic criteria
      in a subset of five hospitals. We generated national age- and gender-adjusted
      estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding
      national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26
      cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive
      care and an additional 130,000 (17.3%) were ventilated in an intermediate care
      unit or cared for in a coronary care unit. Incidence increased >100-fold with age
      (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%,
      or 215,000 deaths nationally, and also increased with age, from 10% in children
      to 38.4% in those >85 yrs old. Women had lower age-specific incidence and
      mortality, but the difference in mortality was explained by differences in
      underlying disease and the site of infection. The average costs per case were
      $22,100, with annual total costs of $16.7 billion nationally. Costs were higher
      in infants, nonsurvivors, intensive care unit patients, surgical patients, and
      patients with more organ failure. The incidence was projected to increase by 1.5%
      per annum. CONCLUSIONS: Severe sepsis is a common, expensive, and frequently
      fatal condition, with as many deaths annually as those from acute myocardial
      infarction. It is especially common in the elderly and is likely to increase
      substantially as the U.S. population ages.

PMID- 11445676
TI  - Accuracy of delayed cultures of plugged telescoping catheter samples for
      diagnosing bacterial pneumonia.
AB  - OBJECTIVE: It is not always feasible to culture immediately bacteriologic samples
      of protected pulmonary specimens on a 24-hr basis before starting antibiotic
      treatment. We have evaluated the effect of delaying the culture of immediate
      plugged telescoping catheter (PTC) samples performed before starting
      antibiotherapy. DESIGN: Prospective paired comparisons study. SETTING: Intensive
      care unit in a university hospital. PATIENTS: Ninety-nine PTCs were performed on
      68 intensive care unit patients suspected of nosocomial or community- acquired
      bacterial pneumonia. INTERVENTION: PTC samples were divided into two aliquots:
      one for immediate (H0) analysis and one for storage at 4 degrees C (H24) for 24
      hrs before being cultured. MEASUREMENTS AND MAIN RESULTS: The results from these
      delayed cultures (H24) were compared with those from immediate ones (H0). All
      negative H0 samples (n = 59) were also negative at H24. Forty PTCs yielded one or
      more microorganisms, with a total of 69 microorganisms in one or both samples. H0
      and H24 cultures were concordant in 119 of 128 (97.9%) cases (kappa coefficient
      value 0.79) with a threshold of 103 colony-forming units (cfu)/mL. Agreement
      between paired cultures was very good. The bias calculated as the mean difference
      between paired culture results was 0.128 +/- 1.024 (Deltalog). Concordance using
      the 103 cfu/mL threshold (102/107 cases, kappa coefficient value 0.82) and
      agreement were enhanced (0.067 +/- 0.645) when possible contaminants were
      excluded (n = 21). CONCLUSIONS: Storing PTC specimens for 24 hrs at 4 degrees C
      is an acceptable alternative when culturing cannot be performed immediately. This
      allows starting antibiotic treatment without any delay.

PMID- 11445678
TI  - Efficacy of a high-carbohydrate diet in catabolic illness.
AB  - OBJECTIVE: To determine within the setting of isocaloric, isonitrogenous enteral
      diets whether a diet that supplies most of its calories from fat or carbohydrate
      would be most beneficial at limiting muscle protein wasting in catabolic illness.
      DESIGN: Prospective, randomized, crossover trial. SETTING: Academic pediatric
      burn unit in tertiary medical center. PATIENTS: Fourteen severely burned (>40%
      total body surface area) children underwent systemic metabolic and cross-leg
      muscle protein kinetic studies. INTERVENTIONS: All were treated clinically in a
      similar manner, including early excision and grafting, antimicrobial therapy, and
      isocaloric, isonitrogenous enteral nutritional support. Subjects randomly
      received either a high-carbohydrate enteral diet (3% fat, 82% carbohydrate, 15%
      protein), or a high-fat enteral diet (44% fat, 42% carbohydrates, 14% protein)
      for 1 week and then crossed over to the other diet for a second week.
      MEASUREMENTS AND MAIN RESULTS: On day 5 of each diet, muscle protein kinetics
      were determined from femoral arterial and venous blood samples during a primed
      constant d5-phenylalanine infusion. Indirect calorimetry was used to determine
      systemic resting energy expenditure and respiratory quotient. The seven boys and
      seven girls were 7.1 +/- 1.1 (mean +/- sem) years old and suffered burns over 65
      +/- 4% of their bodies, with 52 +/- 6% being third-degree burns. Muscle protein
      degradation markedly decreased (p <.01) with administration of the high
      carbohydrate diet. Protein synthesis was unaltered. Endogenous insulin
      concentrations increased during the high-carbohydrate feeding period. No
      differences in energy expenditure were seen between study diets. CONCLUSIONS: In
      severely burned pediatric patients, enteral nutrition supplied predominantly as
      carbohydrate rather than fat improves the net balance of skeletal muscle protein
      across the leg. This is attributable to decreased protein breakdown, suggesting a
      protein-sparing effect of high-carbohydrate feedings.

PMID- 11445679
TI  - Measurement of twitch transdiaphragmatic, esophageal, and endotracheal tube
      pressure with bilateral anterolateral magnetic phrenic nerve stimulation in
      patients in the intensive care unit.
AB  - OBJECTIVE: In the critically ill, respiratory muscle strength usually has been
      assessed by measuring maximum inspiratory pressure. The maneuver is volitional,
      and results can be unreliable. The nonvolitional technique of bilateral
      anterolateral magnetic stimulation of the phrenic nerves, producing twitch
      transdiaphragmatic pressure, has been successful in normal subjects and
      ambulatory patients. In this study we used the technique in the intensive care
      unit and explored the measurement of twitch endotracheal tube pressure as a less
      invasive technique to assess diaphragmatic contractility. DESIGN: Clinical study
      to quantify diaphragm strength in the intensive care unit. SETTING: Patients from
      three London teaching hospital intensive care units and high-dependency units.
      PATIENTS: Forty-one intensive care patients were recruited. Of these, 33 (20 men,
      13 women) were studied. INTERVENTIONS: Esophageal and gastric balloon catheters
      were passed through the anaesthetized nose, and an endotracheal tube occlusion
      device was placed in the ventilation circuit, next to the endotracheal tube. Two
      43-mm magnetic coils were placed anteriorly on the patient's neck, and the
      phrenic nerves were stimulated magnetically. MEASUREMENTS AND MAIN RESULTS: On
      phrenic nerve stimulation, twitch gastric pressure, twitch esophageal pressure,
      twitch transdiaphragmatic pressure, and twitch endotracheal tube pressure were
      measured. Forty-one consecutive patients consented to take part in the study, and
      twitch pressure data were obtained in 33 of these. Mean transdiaphragmatic
      pressure was 10.7 cm H2O, mean twitch esophageal pressure was 6.7 cm H2O, and
      mean twitch endotracheal tube pressure was 6.7 cm H2O. The mean difference
      between twitch esophageal pressure and twitch endotracheal tube pressure was 0.02
      cm H2O. Correlation of the means of twitch endotracheal tube pressure to twitch
      esophageal pressure was 0.93, and that for twitch endotracheal tube pressure to
      transdiaphragmatic pressure was 0.78. CONCLUSIONS: Transdiaphragmatic pressure
      can be measured in the critically ill to give a nonvolitional assessment of
      diaphragm contractility, but not all patients can be studied. At present, the
      relationship of twitch endotracheal tube pressure to transdiaphragmatic pressure
      is too variable to reliably represent a less invasive measure of diaphragm
      strength.

PMID- 11445681
TI  - Role of the molecular adsorbent recycling system (MARS) in the treatment of
      patients with acute exacerbation of chronic liver failure.
AB  - OBJECTIVE: To test the efficacy of the molecular adsorbent recycling system
      (MARS) in patients with acute exacerbation of chronic liver disease. DESIGN: A
      prospective case analysis. SETTING: A university-affiliated tertiary medical
      center. PATIENTS AND METHODS: We applied MARS to treat a consecutive series of
      eight patients with acute exacerbation of chronic liver disease. RESULTS: The
      overall survival rate was 62.5%. All patients demonstrated improvement with
      regard to their degree of encephalopathy. In three patients, intracranial
      pressure and jugular bulb oxygen saturation decreased and cerebral perfusion
      pressure increased after treatment institution. Patients' hyperdynamic state was
      attenuated, as demonstrated by elevation of systemic vascular resistance, mean
      arterial pressure, and parallel reduction in cardiac index. A prompt reduction in
      serum ammonia, bilirubin, and lactate levels was observed. There were no
      complications during the treatment period. CONCLUSIONS: Applying MARS treatments
      to patients with acute exacerbation of chronic liver disease can detoxify blood,
      improve cerebral circulation, and reduce brain edema, as reflected by the
      reduction in intracranial pressure and jugular bulb oxygen saturation values in
      our patients. A partial reversal of the characteristic hyperdynamic circulation
      was also achieved. Despite our encouraging results, further testing is needed to
      determine the reliability of the system.

PMID- 11445682
TI  - Comparison of B-mode ultrasound and computed tomography in the diagnosis of
      maxillary sinusitis in mechanically ventilated patients.
AB  - OBJECTIVE: To compare B-mode ultrasound with sinus computed tomograph (CT) scan
      in the diagnosis of sinusitis in intubated patients undergoing mechanical
      ventilation. DESIGN: Prospective, clinical investigation. SETTING: Medical
      intensive care unit of a university hospital. PATIENTS: Fifty patients undergoing
      intubation and mechanical ventilation more than 2 days, with a clinical suspicion
      of paranasal sinusitis with purulent nasal discharge. INTERVENTIONS: One hundred
      paranasal sinuses were examined. A paranasal CT scan and a B-mode ultrasound were
      performed the same day. Radiologic maxillary sinusitis (RMS) was defined as
      complete opacification of the sinus or as the presence of an air-fluid level.
      Absence of RMS was defined as normal sinus or as the presence of mucosal
      thickening. Important RMS was defined by total opacity or air-fluid level larger
      than half of the sinus area. Moderate RMS was defined by air-fluid level inferior
      than half of the sinus area. For ultrasonographic procedure, the image defined as
      normal was an acoustic shadow arising from the front wall. Two levels of positive
      echography were described: 1) a moderate lesion was defined as the visualization
      only of the hyperechogenic posterior wall of the sinus; 2) an important lesion
      was defined as the hyperechogenic visualization of posterior wall and the
      extension by the internal wall of the sinus outlining the hypoechogenic sinus
      cavity. MEASUREMENTS AND MAIN RESULTS: Sensibility, specificity, positive
      predictive value, and negative predictive value of B-mode ultrasound compared
      with CT were, respectively: 100% (95% confidence intervals [95% CI] = 94.9
      100.0), 96.7% (95% CI = 82.8-99.9), 98.6% (95% CI = 92.4-99.9), and 100% (95% CI
      = 88.1-100). The concordance between a moderate B-mode ultrasound lesion and a
      moderate RMS on CT, and between an important B-mode ultrasound lesion and an
      important RMS on CT, assessed using kappa statistics was 93%. The concordance
      between B-mode ultrasound's results and CT's results assessed using weighted
      kappa statistics was 97%. CONCLUSION: B-mode ultrasound may be proposed first
      line in a ventilated patient with suspicion of maxillary sinusitis.

PMID- 11445683
TI  - Tissue oxygenation and perfusion in patients with systemic sepsis.
AB  - OBJECTIVE: Multiple organ dysfunction is associated with systemic sepsis. To
      investigate whether this is attributable to peripheral tissue hypoperfusion
      and/or cellular hypoxia, simultaneous measurements of tissue perfusion and
      oxygenation were made in patients with severe sepsis and in controls. DESIGN:
      Prospective, observational study. SETTING: Adult intensive care unit, tertiary
      referral center. PATIENTS: Volunteers (group C, n = 7), patients undergoing
      cardiopulmonary bypass (group B, n = 6), and patients with severe sepsis (group
      S, n = 6). INTERVENTIONS: Limb ischemia and reperfusion. MEASUREMENTS AND MAIN
      RESULTS: Tissue oxygenation and microvascular flow were measured by using
      microelectrodes inserted into brachoradialis muscle and overlying subcutaneous
      tissue. Forearm cutaneous red cell flux and regional blood flow were measured
      simultaneously. Responses to 20 mins of limb ischemia and subsequent reperfusion
      were observed. Baseline muscle tissue oxygenation was greater in sepsis (1.7 +/-
      0.2, 1.5 +/- 0.7, and 4.4 +/- 0.6 kPa for groups C, B, and S, respectively, mean
      +/- sem, p <.05), although baseline subcutaneous tissue oxygenation did not vary
      between groups. During ischemia tissue oxygenation, values decreased in muscle
      (to 1.3 +/- 0.2, 1.0 +/- 0.4, and 1.5 +/- 0.4 kPa for groups C, B, and S,
      respectively) and subcutaneous tissue (to 2.0 +/- 0.3, 1.7 +/- 0.5, and 2.3 +/-
      0.2 kPa for groups C, B, and S, respectively). Decline in tissue oxygen tension
      was initially more rapid in septic muscle compared with controls (25% decrease,
      68 +/- 23 vs. 176 +/- 38 for group S vs. group C, p <.05, and 50% decrease, 126
      +/- 34 vs. 398 +/- 72 secs for group S vs. group C, p <.01). However, overall
      rate of tissue decline was similar (95% decrease, 444 +/- 122 vs. 614 +/- 96 for
      group S vs. group C, p >.05). After reperfusion, significant differences in
      muscle tissue oxygenation reappeared between groups (2.0 +/- 0.3, 1.5 +/- 0.7,
      and 4.0 +/- 0.4 kPa for groups C, B, and S, respectively, p <.05). There were no
      differences in time to 25%, 50%, or 95% tissue oxygen recovery. Whole limb
      reperfusion was significantly less in patient groups compared with controls (10.6
      +/- 0.9, 4.5 +/- 1.2, and 4.3 +/- 1.6 mL x 100 mL(-1) x min(-1) for groups C, B,
      and S, respectively, p <.05). CONCLUSIONS: Significant differences in tissue
      oxygenation distribution between muscle and subcutaneous tissues occur in
      patients with severe sepsis. High baseline muscle tissue oxygen levels are
      accompanied by rapid extraction of oxygen during stagnant ischemia.

PMID- 11445684
TI  - Co-amoxiclav pharmacokinetics during posttraumatic hemorrhagic shock.
AB  - OBJECTIVE: To determine the effects of severe trauma with hemorrhagic shock on
      amoxicillin and clavulanate concentrations in plasma and their pharmacokinetics.
      DESIGN: A prospective, open, descriptive study. SETTING: A 12-bed, adult surgical
      intensive care unit in a university-affiliated hospital in France. SUBJECTS:
      Subjects were 12 patients (10 men, 2 women) with severe trauma: median (range)
      Injury Severity Score, 38 (17-48); Acute Physiology and Chronic Health Evaluation
      II, 16 (7-38); Simplified Acute Physiology Score II, 41 (23-77). Also enrolled
      were 12 healthy volunteers who were matched on age (+/-5 yrs), gender, and body
      surface area (+/-20 cm2). All the trauma patients suffered hemorrhagic shock
      defined as the association of at least one episode of systolic blood pressure <90
      mm Hg and an intravascular volume expansion >2000 mL between trauma and surgery.
      INTERVENTION: Prophylactic perioperative administration of 2 g of amoxicillin and
      0.2 g of clavulanate in combination during the first 12 hrs posttrauma in
      patients, and at the start of the pharmacokinetic study in volunteers.
      MEASUREMENTS AND MAIN RESULTS: Serial plasma samples (n = 13) were obtained after
      the first antibiotic administration to measure antibiotic levels by using high
      performance liquid chromatography assays. Compared with volunteers, trauma
      patients had higher plasma amoxicillin and clavulanate concentrations, attributed
      to a reduction of the volume of distribution (p =.001 and p =.06, respectively)
      and, to a lesser extent, of the total body clearance (p =.09 and p =.20,
      respectively). Consequently, amoxicillin and clavulanate elimination half-lives
      were similar for the two groups of subjects. The interindividual variabilities
      for all the amoxicillin pharmacokinetic parameters were higher in patients.
      CONCLUSIONS: In trauma patients with hemorrhagic shock requiring surgery, the
      administration of 2 g of amoxicillin and 0.2 g of clavulanate seems adequate,
      according to the antibiotic concentrations observed in plasma for both drugs.
      However, further studies exploring antibiotic concentrations in tissues are
      warranted.

PMID- 11445686
TI  - Forgoing life-sustaining treatments: how the decision is made in French pediatric
      intensive care units.
AB  - OBJECTIVES: The decision to forgo life support is frequently made in pediatric
      intensive care units (PICUs). A group of experts is currently preparing
      recommendations for guidelines concerning this decision-making process in France.
      We have performed a prospective study to help the experts. This study documents
      how children die in French PICUs and how the decision to limit life support is
      made. DESIGN: A multicenter, prospective, cross-sectional study. SETTING: Thirty
      three multidisciplinary PICUs in university hospitals. PATIENTS: All consecutive
      deaths were recorded over a 4-month period. Children who died after a medical
      decision to forgo life-sustaining treatment were included in group 1 and children
      who died from other causes were included in group 1. MAIN RESULTS: A total of 264
      consecutive children died, 40.1% from group 1 and 59.8% from group 2. Patients of
      both groups were primarily admitted for acute respiratory failure (group 1,
      50.8%; group 2, 52.6%). Neurologic emergencies were more frequent in patients in
      group 1, whereas patients with cardiovascular failures were more frequent in
      group 2. When there was a question of whether to pursue life-sustaining
      treatment, the parents' opinions were recorded in 72.1% of cases. A specific
      meeting was called to make this decision in 80.1% of cases. This meeting involved
      the medical staff in all cases. Parents were aware of the meeting in 10.7% of
      cases. The conclusion of the meeting was reported to the parents in 18.7% of
      cases and documented in the patient's medical record in 16% of cases. Experts who
      were not members of the PICU staff were invited to give their opinion in 62.2% of
      cases. CONCLUSIONS: The decision to forgo life-sustaining treatment is frequently
      made for children dying in French PICUs. Guidelines must be available to help the
      medical staff reach this decision. Knowledge of the decision-making process in
      French PICUs provides the experts with information needed to elaborate such
      recommendations.

PMID- 11445688
TI  - Prospective trial of high-frequency oscillation in adults with acute respiratory
      distress syndrome.
AB  - OBJECTIVE: To evaluate the safety and efficacy of high-frequency oscillatory
      ventilation (HFOV) in adult patients with the acute respiratory distress syndrome
      (ARDS) and oxygenation failure. DESIGN: Prospective, clinical study. SETTING:
      Intensive care and burn units of two university teaching hospitals. PATIENTS:
      Twenty-four adults (10 females, 14 males, aged 48.5 +/- 15.2 yrs, Acute
      Physiology and Chronic Health Evaluation II score 21.5 +/- 6.9) with ARDS (lung
      injury score 3.4 +/- 0.6, Pao2/Fio2 98.8 +/- 39.0 mm Hg, and oxygenation index
      32.5 +/- 19.6) who met one of the following criteria: Pao2 < or =65 mm Hg with
      Fio2 > or =0.6, or plateau pressure > or =35 cm H2O. INTERVENTIONS: HFOV was
      initiated in patients with ARDS after varying periods of conventional ventilation
      (CV). Mean airway pressure (Paw) was initially set 5 cm H2O greater than Paw
      during CV, and was subsequently titrated to maintain oxygen saturation between
      88% and 93% and Fio2 < or =0.60. MEASUREMENTS AND MAIN RESULTS: Fio2, Paw,
      pressure amplitude of oscillation, frequency, blood pressure, heart rate, and
      arterial blood gases were monitored during the transition from CV to HFOV, and
      every 8 hrs thereafter for 72 hrs. In 16 patients who had pulmonary artery
      catheters in place, cardiac hemodynamics were recorded at the same time
      intervals. Throughout the HFOV trial, Paw was significantly higher than that
      applied during CV. Within 8 hrs of HFOV application, and for the duration of the
      trial, Fio2 and Paco2 were lower, and Pao2/Fio2 was higher than baseline values
      during CV. Significant changes in hemodynamic variables following HFOV initiation
      included an increase in pulmonary artery occlusion pressure (at 8 and 40 hrs) and
      central venous pressure (at 16 and 40 hrs), and a reduction in cardiac output
      throughout the course of the study. There were no significant changes in systemic
      or pulmonary pressure associated with initiation and maintenance of HFOV.
      Complications occurring during HFOV included pneumothorax in two patients and
      desiccation of secretions in one patient. Survival at 30 days was 33%, with
      survivors having been mechanically ventilated for fewer days before institution
      of HFOV compared with nonsurvivors (1.6 +/- 1.2 vs. 7.8 +/- 5.8 days; p =.001).
      CONCLUSIONS: These findings suggest that HFOV has beneficial effects on
      oxygenation and ventilation, and may be a safe and effective rescue therapy for
      patients with severe oxygenation failure. In addition, early institution of HFOV
      may be advantageous.

PMID- 11445689
TI  - Evaluation of delirium in critically ill patients: validation of the Confusion
      Assessment Method for the Intensive Care Unit (CAM-ICU).
AB  - OBJECTIVE: To develop and validate an instrument for use in the intensive care
      unit to accurately diagnose delirium in critically ill patients who are often
      nonverbal because of mechanical ventilation. DESIGN: Prospective cohort study.
      SETTING: The adult medical and coronary intensive care units of a tertiary care,
      university-based medical center. PATIENTS: Thirty-eight patients admitted to the
      intensive care units. MEASUREMENTS AND MAIN RESULTS: We designed and tested a
      modified version of the Confusion Assessment Method for use in intensive care
      unit patients and called it the CAM-ICU. Daily ratings from intensive care unit
      admission to hospital discharge by two study nurses and an intensivist who used
      the CAM-ICU were compared against the reference standard, a delirium expert who
      used delirium criteria from the Diagnostic and Statistical Manual of Mental
      Disorders (fourth edition). A total of 293 daily, paired evaluations were
      completed, with reference standard diagnoses of delirium in 42% and coma in 27%
      of all observations. To include only interactive patient evaluations and avoid
      repeat-observer bias for patients studied on multiple days, we used only the
      first-alert or lethargic comparison evaluation in each patient. Thirty-three of
      38 patients (87%) developed delirium during their intensive care unit stay, mean
      duration of 4.2 +/- 1.7 days. Excluding evaluations of comatose patients because
      of lack of characteristic delirium features, the two critical care study nurses
      and intensivist demonstrated high interrater reliability for their CAM-ICU
      ratings with kappa statistics of 0.84, 0.79, and 0.95, respectively (p <.001).
      The two nurses' and intensivist's sensitivities when using the CAM-ICU compared
      with the reference standard were 95%, 96%, and 100%, respectively, whereas their
      specificities were 93%, 93%, and 89%, respectively. CONCLUSIONS: The CAM-ICU
      demonstrated excellent reliability and validity when used by nurses and
      physicians to identify delirium in intensive care unit patients. The CAM-ICU may
      be a useful instrument for both clinical and research purposes to monitor
      delirium in this challenging patient population.

PMID- 11445691
TI  - Cardiac variability in critically ill adults: influence of sepsis.
AB  - OBJECTIVE: To evaluate, in critically ill adults, factors associated with
      impaired sympathovagal balance. DESIGN: One-month inception cohort study.
      SETTING: Twenty-six-bed medical intensive care unit of a teaching hospital.
      PATIENTS: Critically ill adults with an expected duration of intensive care unit
      stay of > or =48 hrs were enrolled. Patients with permanent arrhythmia or cardiac
      pacing were not included. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS:
      Sympathovagal balance was assessed on the day after intensive care unit admission
      by the low-frequency/high-frequency ratio obtained from spectral components of
      heart rate signal: overall variability, low frequency, and high frequency.
      RESULTS: Forty-one patients, 13 with sepsis and 28 without sepsis, were assessed.
      Predictors of low-frequency/high-frequency ratio with the automatic interaction
      detection method were sepsis and age. Binary logit analysis adjusted for age
      showed that sepsis remained a strong and independent factor of a low
      frequency/high-frequency ratio of <1.50, with an odds ratio of 3.63 (95%
      confidence interval, 1.47-9.01, p =.005). Use of mechanical ventilation,
      catecholamines, or sedation did not add any information. The use of the low
      frequency/high-frequency ratio in diagnosing sepsis may be supported by a
      likelihood ratio for low frequency/high frequency <1 at 6.47. CONCLUSIONS: This
      work suggests that impaired cardiac variability and notably sympathovagal balance
      (i.e., a low-frequency/high-frequency ratio <1.0) may be a diagnostic test for
      sepsis.

PMID- 11445692
TI  - Usefulness of plasma exchange plus continuous hemodiafiltration to reduce adverse
      effects associated with plasma exchange in patients with acute liver failure.
AB  - OBJECTIVE: To efficiently remove middle-molecular-weight substances such as
      hepatic toxins and minimize adverse effects associated with plasma exchange
      implementation, we have performed plasma exchange slowly in combination with
      continuous hemodiafiltration. This study was designed to determine the usefulness
      of plasma exchange with continuous hemodiafiltration in reducing the adverse
      effects associated with implementation of plasma exchange alone. DESIGN: A
      retrospective clinical study. SETTING: University teaching hospital. PATIENTS:
      The study involved 90 patients with liver failure who had been treated with
      plasma exchange in our department over the past 12 yrs. We examined these
      patients by dividing them into two groups (48 patients treated with plasma
      exchange alone and 42 patients treated with plasma exchange plus continuous
      hemodiafiltration at the time of plasma exchange implementation). MEASUREMENTS
      AND MAIN RESULTS: Baseline blood Na+ concentration, HCO3- concentration, and
      colloid osmotic pressure were followed after implementation of plasma exchange to
      compare the frequency of development of three adverse effects (hypernatremia,
      metabolic alkalosis, and sharp decrease in colloid osmotic pressure) in the two
      groups. Hypernatremia was found in 26.7% of treatments in the group with plasma
      exchange alone and 3.3% in the group of plasma exchange plus continuous
      hemodiafiltration, and metabolic alkalosis was found in 30.6% of treatments in
      the group with plasma exchange alone and 4.9% in the group of plasma exchange
      plus continuous hemodiafiltration; both percentages were significantly higher in
      the group with plasma exchange alone (p <.001). A sharp decrease in colloid
      osmotic pressure occurred in 13.3% of treatments in the group with plasma
      exchange alone but was not observed at all in the patients treated with plasma
      exchange plus continuous hemodiafiltration. CONCLUSIONS: We conclude that adverse
      effects associated with plasma exchange for artificial liver support for liver
      failure can be alleviated with use of plasma exchange plus continuous
      hemodiafiltration instead of plasma exchange alone.

PMID- 11445693
TI  - Splanchnic perfusion during hemodialysis: evidence for marginal tissue perfusion.
AB  - OBJECTIVE: Splanchnic perfusion may be compromised during hemodialysis because of
      hypovolemia, inflammatory response, and blood flow redistribution. The aim of
      this study was to assess the response of splanchnic blood flow and oxygen
      transport to hemodialysis. DESIGN: A prospective clinical study. SETTING: A mixed
      medical-surgical intensive care unit in a university hospital. PATIENTS: Nine
      patients with acute renal failure. INTERVENTIONS: A 4-hr period of hemodialysis.
      MEASUREMENTS AND MAIN RESULTS: Systemic (via a pulmonary artery catheter),
      hepatosplanchnic, and femoral (via dye dilution) blood flow and gastric mucosal
      Pco2 were measured before, during, and 2 hrs after hemodialysis. During
      hemodialysis, despite unchanged arterial blood pressure, cardiac output and
      stroke volume decreased from 3.0 +/- 1.0 L/m2/min (mean +/- sd) to 2.3 +/- 0.7
      L/m2/min (p =.02), and from 38 +/- 16 mL/m2/min to 28 +/- 12 mL/m2/min (p =.01),
      respectively. Splanchnic but not femoral blood flow decreased from 0.9 +/- 0.3
      L/m2/min to 0.7 +/- 0.2 L/m2/min (p =.02). The blood flows returned to baseline
      values after dialysis without need for therapeutic interventions. Gastric mucosal
      arterial Pco2 gradients were high before dialysis (35 +/- 23 torr [4.6 +/- 3.1
      kPa]) and did not change. Renin but not atrial natriuretic peptide concentration
      increased during hemodialysis from 13 +/- 13 microg/L to 35 +/- 40 microg/L and
      decreased afterward to baseline values (13 +/- 13 microg/L; p =.01). Whereas
      interleukin 6 tended to decrease, tumor necrosis factor alpha increased during
      hemodialysis from 74 +/- 24 pg/mL to 86 +/- 31 pg/mL and continued to increase
      after hemodialysis to 108 +/- 66 pg/mL (p =.022). CONCLUSION: Hemodialysis and
      fluid removal in normotensive patients with acute renal failure may result in a
      reduction of systemic and splanchnic blood flow that is undetectable using
      traditional clinical signs. In contrast to what is observed in hypovolemia, the
      changes in regional blood flow are rapidly reversible after hemodialysis.

PMID- 11445695
TI  - Difference in time to positivity of hub-blood versus nonhub-blood cultures is not
      useful for the diagnosis of catheter-related bloodstream infection in critically
      ill patients.
AB  - OBJECTIVE: The differential time to positivity (DTTP), defined as the difference
      in time necessary for the blood cultures taken by a peripheral puncture and
      through the catheter to become positive has been suggested to be useful in
      differentiating between catheter-related bloodstream infection (CR-BSI) and other
      sources of bacteremia. A DTTP of >120 mins was found predominantly in CR-BSI. The
      objective of our study was to investigate whether DTTP is useful for the
      diagnosis of CR-BSI in a medical-surgical intensive care unit. DESIGN:
      Prospective clinical study. SETTING: A 60-bed medical-surgical intensive care
      unit of a university hospital. PATIENTS: One hundred consecutive adult patients
      from whom catheter(s) were to be removed for suspected CR-BSI were studied.
      INTERVENTION: A blood culture (using aerobic and anaerobic culture bottles) was
      first taken from a new puncture site. Next, a blood culture was taken through
      every intravascular catheter in place. MEASUREMENTS AND RESULTS: DTTP was
      calculated using the automated BacT/Alert blood culture system. Three patients
      had CR-BSI and nine patients had noncatheter-related bacteremia. Five patients
      had catheter-related sepsis without proven bacteremia. There was no significant
      difference in median DTTP between patients with CR-BSI and noncatheter-related
      bacteremia (2.1 hrs and 3.3 hrs, respectively; p =.6). Moreover, catheter-related
      sepsis in patients without bacteremia could not be detected using DTTP.
      CONCLUSION: DTTP seems not to be useful for the diagnosis of CR-BSI in a medical
      surgical intensive care unit.

PMID- 11445697
TI  - Circulating levels of the long pentraxin PTX3 correlate with severity of
      infection in critically ill patients.
AB  - OBJECTIVE: To evaluate the recently discovered long pentraxin PTX3 in plasma of
      critically ill patients and to compare it with the classic short pentraxin C
      reactive protein and with other indicators of inflammation. DESIGN: A cohort
      study on plasma samples. SETTING: Medical intensive care unit (ICU) of the
      University Hospital of Basel. PATIENTS: A total of 101 consecutive critically ill
      patients admitted to the medical ICU. INTERVENTIONS: Venous blood samples were
      routinely obtained at entry, on day 2, and at discharge or before death.
      MEASUREMENTS AND MAIN RESULTS: Plasma samples were obtained from 101 consecutive
      critically ill patients admitted to the ICU with systemic inflammatory response
      syndrome, sepsis, or septic shock. PTX3 plasma levels were measured by enzyme
      linked immunosorbent assay. PTX3 was elevated in critically ill patients, with a
      gradient from systemic inflammatory response syndrome to septic shock. PTX3
      levels correlated with clinical scores reflecting severity of disease (e.g.,
      Acute Physiology and Chronic Health Evaluation II: p =.00097). In addition, high
      levels of PTX3 were associated with unfavorable outcome. CONCLUSIONS: The long
      pentraxin PTX3 is elevated in critically ill patients and correlates with
      severity of disease and infection. Compared with the short pentraxin C-reactive
      protein, PTX3 may be a more direct indicator of tissue involvement by
      inflammatory and infectious processes.

PMID- 11445698
TI  - Functional status and quality of life in long-term survivors of cardiac arrest
      after cardiac surgery.
AB  - OBJECTIVE: To assess long-term survival, functional status, and quality of life
      in patients who experienced cardiac arrest after cardiac surgery. DESIGN:
      Prospective, observational study. SETTING: An 18-bed, adult cardiac surgery
      intensive care unit in a tertiary teaching center. PATIENTS: Twenty-nine cardiac
      surgery patients who suffered an unexpected cardiac arrest in the immediate
      postoperative period. INTERVENTIONS: The New York Heart Association
      classification and a questionnaire based on the Nottingham Health Profile were
      used to evaluate functional status and quality of life 4 yrs after hospital
      discharge. MEASUREMENTS AND MAIN RESULTS: Of the 29 patients who experienced
      cardiac arrest during the first 24 hrs after cardiac surgery, 27 patients (93%)
      were successfully resuscitated and 23 patients (79%) survived to hospital
      discharge. Evaluation 4 yrs postdischarge showed that, of the 29 patients, 16
      patients (55%) were still alive (long-term survivors). Functional status
      assessment of long-term survivors revealed that 12 patients (75%) were grouped in
      New York Heart Association class I, 3 patients (19%) in class II, and 1 patient
      (6%) in class III. None of them had a neurologic deficit. They all were living
      independently at home, without need of any nursing care. No patient reported any
      abnormal emotional reactions, and six patients (38%) had mild sleep disturbances,
      such as early awaking. Regarding activities of daily living, 20% returned to
      work, 94% were able to look after their home, 96% had a social life, 63% were
      sexually active, 81% were involved in their hobbies, and 75% had gone on
      holidays. CONCLUSIONS: Cardiac surgery patients who experience an unexpected
      cardiac arrest in the immediate postoperative period have a 55% chance of being
      alive 4 yrs postdischarge. The majority of these long-term survivors has a good
      outcome with respect to functional status and quality of life.

PMID- 11445699
TI  - Effects of iloprost, a stable prostacyclin analog, on intestinal leukocyte
      adherence and microvascular blood flow in rat experimental endotoxemia.
AB  - OBJECTIVE: To investigate the effects of iloprost, a stable prostacyclin analog,
      on leukocyte adherence in intestinal venules and intestinal microvascular blood
      flow in experimental endotoxemia. DESIGN: Prospective, randomized, controlled
      animal study. SETTING: Experimental laboratory. SUBJECTS: Twenty-one male Wistar
      rats weighing 190 +/- 40 g. INTERVENTIONS: The rats were divided equally into
      three groups: the first was a control group; the second received endotoxin (20
      mg/kg lipopolysaccharide from Escherichia coli O55:B5 intravenously); and the
      third received endotoxin and intravenous iloprost infusion (2 ng.kg-1.min-1).
      MEASUREMENTS AND MAIN RESULTS: The distal small intestine of the animals was
      examined by using intravital fluorescence videomicroscopy 2 hrs after endotoxin
      challenge. Leukocytes were stained in vivo by means of rhodamine 6G. Intestinal
      microvascular blood flow was measured by laser Doppler flowmetry in the terminal
      ileum. Iloprost treatment significantly attenuated the count of adherent
      leukocytes in collecting venules (control, 61 +/- 10 n/mm2; lipopolysaccharide,
      364 +/- 60 n/mm2; iloprost, 232 +/- 29 n/mm2; p <.05) and in postcapillary
      venules (control, 96 +/- 14 n/mm2; lipopolysaccharide, 470 +/- 21 n/mm2; iloprost
      390 +/- 41 n/mm2; p <.05). Intestinal microvascular blood flow was decreased
      significantly in the lipopolysaccharide group (-49%), whereas iloprost-treated
      animals showed no significant difference compared with the control group.
      CONCLUSIONS: The study demonstrated that administration of iloprost attenuated
      leukocyte adherence in postcapillary and collecting intestinal venules and
      improved intestinal microvascular blood flow. Thus, iloprost treatment may impact
      endotoxin-induced intestinal injury.

PMID- 11445701
TI  - Surfactant phosphatidylcholine in thermally injured pigs.
AB  - OBJECTIVE: To investigate the effect of a thermal injury on pulmonary surfactant
      phosphatidylcholine kinetics. DESIGN: Random, controlled study. SETTING:
      University research laboratory. SUBJECTS: Yorkshire swine (n = 8) with and
      without a 40% total body surface area burn. INTERVENTIONS: A new isotope tracer
      methodology was used to quantify surfactant phosphatidylcholine kinetics. Four
      days after burn, [1,2-13C2]acetate and [U-(13)C16]palmitate were infused
      continuously for 8 hrs to quantify surfactant phosphatidylcholine synthesis,
      secretion, recycling, and irreversible loss. MEASUREMENTS AND MAIN RESULTS: The
      total surfactant phosphatidylcholine pool size was reduced from the control value
      of 2.65 +/- 0.05 to 1.61 +/- 0.08 micromol/g wet lung in burned animals (p <.05),
      as was the proportional contribution of palmitate to lung surfactant
      phosphatidylcholine composition. This reduction was associated with a significant
      decrease in lung dynamic compliance from the control value of 66 +/- 6 to 55 +/-
      6 mL/cm H2O for burned pigs (p <.05). The most prominent response of lung
      phosphatidylcholine kinetics was a decrease in the total lung phosphatidylcholine
      synthesis from a control value of 12.7 +/- 1.2 to 5.5 +/- 0.3 nmol
      phosphatidylcholine-bound palmitate x hr(-1) x g of wet lung(-1) in burned
      animals (p<.05). CONCLUSIONS: Pulmonary phosphatidylcholine content and palmitate
      composition decrease after burn injury because of a decrease in the rate of
      phosphatidylcholine synthesis. These responses likely contribute to impaired lung
      compliance.

PMID- 11445702
TI  - Attenuation of sepsis-related immunoparalysis by continuous veno-venous
      hemofiltration in experimental porcine pancreatitis.
AB  - OBJECTIVES: In light of evidence suggesting that hemofiltration favorably
      influences septic diseases by removing sepsis mediators, the impact of different
      modalities of continuous veno-venous hemofiltration (CVVH) on outcome and
      immunologic derangements in porcine pancreatogenic sepsis was evaluated. DESIGN:
      Randomized, controlled intervention trial. SUBJECTS: Forty-eight minipigs of
      either sex. INTERVENTIONS: Pancreatitis was induced by intraductal injection of
      sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW).
      Animals were allocated either to untreated controls-group 1-or to one of three
      treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of
      hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4:
      high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival
      represented the major parameter of the study. Serum cytokine levels, sepsis
      related down-regulation of major histocompatibility complex II and CD14
      expression on leukocytes, bacterial translocation, and endotoxemia were further
      parameters evaluated in the study. MEASUREMENTS AND MAIN RESULTS: High-volume
      CVVH combined with periodic filter change was significantly superior compared
      with less intensive treatment modalities (low-volume CVVH, no filter change) in
      sepsis protection. Long-term survival (>60 hrs) was found in 67% of group 4 and
      33% of group 3 animals (p <.05), whereas in controls and group 2 no animal
      survived. CVVH ameliorated the initial serum tumor necrosis factor-alpha response
      and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down
      regulation of major histocompatibility complex II and CD14 expression on
      monocytes was significantly improved by CVVH. Improved oxidative burst and
      phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte
      function was stabilized by CVVH. Also, CVVH significantly reduced bacterial
      translocation and endotoxemia. CONCLUSIONS: Hemofiltration reversed sepsis
      induced immunoparalysis in a porcine model of bile acid-induced pancreatitis.
      Implications for human pancreatitis must be validated in prospective, clinical
      protocols.

PMID- 11445704
TI  - Protegrin-1 enhances bacterial killing in thermally injured skin.
AB  - OBJECTIVE: Septic complications and the emergence of drug-resistant microbes
      represent serious risks to patients. Recently, naturally occurring peptides have
      been discovered that possess potent and broad-spectrum antimicrobial activity.
      Protegrin-1 is particularly attractive for clinical use in human wounds because,
      unlike defensins, protegrin-1 retains broad antimicrobial and antifungal activity
      at physiologic salt concentration and in the presence of serum. The objective of
      this study was to examine the efficacy of protegrin-1 in killing multiple drug
      resistant microbes isolated from human burn patients. DESIGN: For thein
      vitroexperiment, bilayer radial diffusion was performed comparing standard
      antibiotics with protegrin-1 on multiple-drug-resistant microbial organisms
      isolated from infected burn wounds. In vivo, rats received a 20% total body
      surface area partial-thickness burn by immersion in 60 degrees C water for 20
      secs followed by wound seeding with 106 colony forming units of Silvadene
      resistant Pseudomonas aeruginosa. SETTING: University of Michigan research
      laboratory. SUBJECTS: Adult, male Sprague-Dawley rats. INTERVENTIONS: Rats were
      randomized into three groups: those receiving synthetic protegrin-1, acetic acid
      (carrier), or gentamicin (positive control). Protegrin-1 was administered by
      topical application or intradermal injection. Wound tissues were harvested
      aseptically at different time points for quantitative bacterial counts.
      MEASUREMENTS AND MAIN RESULTS: In vivo and in vitro experiments revealed rapid
      and significant decreases in bacterial counts for protegrin-1-treated groups
      compared with controls. CONCLUSIONS: This study shows that protegrin-1
      potentially may be used as an alternative or adjunct therapy to standard agents
      used to treat wound infections.

PMID- 11445705
TI  - Application of fiberoptic sensors for the study of hepatic dysoxia in swine
      hemorrhagic shock.
AB  - OBJECTIVES: To determine whether the simultaneous measurement of tissue pH, Pco2,
      and Po2 with a multiple-parameter fiberoptic sensor can be used to indicate the
      onset of hepatic dysoxia, to determine critical values, and to assess their use
      in predicting negative outcomes. DESIGN: Prospective animal study. SETTING:
      University research laboratory. SUBJECTS: Fourteen Yorkshire swine.
      INTERVENTIONS: Hemorrhagic shock (n = 11) was induced over 15 mins to lower
      systolic blood pressure to 40 mm Hg and was maintained for 30, 60, or 90 mins.
      Resuscitation was achieved with shed blood and warm saline to maintain mean
      pressure >60 mm Hg for 120 mins. Sham animals (n = 3) were subjected to 90 mins
      of sham shock, followed by a 120-min recovery period. MEASUREMENTS AND MAIN
      RESULTS: The multiple-parameter sensor continuously measured tissue pH, Pco2, and
      Po2. pH and Pco2, indicators of anaerobic metabolism, were plotted against tissue
      Po2. All shocked animals, but no sham animals, showed a biphasic relationship
      between Po2 and both pH and Pco2. Curves were fit to both an exponential and a
      dual-line linear function to determine critical values for Po2, pH, and Pco2. The
      length of time the animal was dysoxic was evaluated as a predictor of negative
      outcome. Critical values determined from the exponential models were more
      sensitive indicators of negative outcome than values determined from the linear
      model and more sensitive than arterial lactate and tonometric intramucosal pH and
      Pco2. CONCLUSIONS: The multiple-parameter sensor offers the unique opportunity to
      study solid as well as hollow organ dysoxia through the simultaneous measurement
      of interstitial pH, Pco2, and Po2 in a small tissue region. The gradual
      transition from sufficient oxygen availability to dysoxia as a result of
      hemorrhage was better described by an exponential equation. The length of time
      that pH was below or Pco2 was above the critical value determined from the
      exponential model was predictive of a negative outcome.

PMID- 11445706
TI  - Prostacyclin is neither sufficient alone nor necessary to cause pulmonary
      dysfunction: results from infusions of prostacyclin and antiprostacyclin antibody
      in porcine septic shock.
AB  - OBJECTIVE: This study evaluated whether prostacyclin is a necessary mediator of
      inflammation in graded bacteremia or is sufficient alone in pathophysiologic
      concentrations to cause the pulmonary derangement of bacteremic shock. DESIGN:
      Experimental. SETTING: Laboratory. SUBJECTS: Twenty-three anesthetized adult
      swine. INTERVENSIONS: Swine were studied in four groups for 4 hrs: a) an
      anesthesia control group (n = 6); b) a septic control group (n = 6), in which
      1010/mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg-1.hr-1 and
      increased to 4.0 mL.kg-1.hr-1 over 3 hrs; c) a prostacyclin infusion group (n =
      6), which received prostacyclin infusion to match septic control plasma
      concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group
      (n = 5), which received continuous Aeromonas hydrophila infusion plus
      antiprostacyclin antibody infusion. MEASUREMENTS AND MAIN RESULTS: Pulmonary
      hemodynamics, arterial blood gases, and plasma concentrations of arachidonate
      metabolites were measured hourly over a 4-hr period. In the septic control group
      and antiprostacyclin antibody group, elevated pulmonary vascular resistance index
      and pulmonary artery pressure with decreased Pao2, as well as lower pH, were
      documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia
      control group and prostacyclin infusion group (p <.05). Thromboxane B2
      concentration increased significantly in all groups during septic shock. In the
      antiprostacyclin antibody group, leukotriene B4 increased immediately after
      starting antiprostacyclin antibody infusion and reached significance at 3 hrs
      compared with the septic control group (p <.05). The prostacyclin infusion group
      had consistently lower concentrations of leukotrienes C4, D4, and E4 than all
      other groups. CONCLUSIONS: Prostacyclin does not mediate blood gas changes,
      alterations of pulmonary hemodynamics, or platelet abnormalities in porcine
      septic shock, because antiprostacyclin antibody infusion did not change the
      pulmonary hypertension and hypoxemia, and infusion of prostacyclin to
      pathophysiologic blood concentrations did not reproduce such changes.
      Antiprostacyclin blockade during bacteremia significantly increased
      concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas
      prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4,
      suggesting that endogenous prostacyclin may blunt leukotriene release.

PMID- 11445707
TI  - Effect of recombinant bactericidal/permeability-increasing protein on endotoxin
      translocation and lipopolysaccharide-binding protein/CD14 expression in rats
      after thermal injury.
AB  - OBJECTIVE: To investigate the potential mechanisms underlying the in vivo effect
      of recombinant bactericidal/permeability-increasing protein (rBPI21) on
      endogenous bacteria or endotoxin translocation and lipopolysaccharide-binding
      protein/CD14 expression secondary to thermal injury. DESIGN: Prospective,
      randomized, controlled animal study. SETTING: College hospital animal research
      laboratory. SUBJECTS: Thirty-six male Wistar rats weighing 250-300 g.
      INTERVENTIONS: The rats were anesthetized, and a 35% total body surface area full
      thickness burn was created. Animals were randomized to receive treatment with
      either rBPI21 or the control protein (albumin). rBPI21 (2 mg/kg body wt, BPI
      group) or a protein control preparation (burn group) in the same dose was
      administered in an intravenous bolus at 30 mins and 4 hrs after thermal injury.
      All animals were killed at 12 and 24 hrs postburn (six to ten rats for each
      interval). In addition, eight rats were taken as normal controls. MEASUREMENT AND
      MAIN RESULTS: Our data showed that treatment with rBPI21 was effective in
      preventing endotoxin translocation secondary to severe burns. Meanwhile, tissue
      lipopolysaccharide-binding protein, CD14, and tumor necrosis factor-alpha mRNA
      expression in various organs were inhibited markedly by rBPI21 secondary to acute
      insults (p <.05-.01). Furthermore, significant reduction in serum aminoleucine
      transferase concentrations and elevation in intestinal diamine oxidase activities
      in the rBPI21-treated group were found compared with controls (p <.05-.01).
      CONCLUSIONS: These findings indicate that endotoxin accumulated in local sites
      after thermal injury can markedly up-regulate lipopolysaccharide-binding
      protein/CD14 and tumor necrosis factor-alpha mRNA expression in various organs.
      Meanwhile, up-regulation of lipopolysaccharide-binding protein/CD14 expression
      would be the major molecular mechanism of increasing sensitivity to endogenous
      endotoxin response after burns. Early treatment with rBPI21may be effective in
      attenuating multiple organ damage resulting from gut-origin endotoxin
      translocation. This might be associated with the down-regulation effects of
      tissue lipopolysaccharide-binding protein and CD14 gene expression by the use of
      rBPI21.

PMID- 11445708
TI  - Maternal magnesium sulfate treatment is associated with reduced brain-blood flow
      perfusion in preterm infants.
AB  - OBJECTIVE: To examine the influence of antenatally administered magnesium sulfate
      (MgSO4) and ritodrine on cerebral blood flow and systemic hemodynamics in preterm
      infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive
      care unit of a university central hospital. PATIENTS: Fifty-five preterm infants
      age <33 wks of gestation. INTERVENTIONS: Serial Doppler examinations of the brain
      circulation, heart rate, systemic blood pressure, and echocardiographic
      assessment of ductus arteriosus shunting were performed during the first week of
      life in infants exposed antenatally to maternal MgSO4 (n = 19) or ritodrine
      treatment (n = 17), and in 19 nonexposed preterm controls. MEASUREMENTS AND MAIN
      RESULTS: Cerebral blood flow velocity measurements were obtained from the
      anterior cerebral artery and internal carotid artery. Perfusion pressure and
      indices of resistance and blood flow in both vessels were subsequently derived.
      Maternal MgSO4 had no effect on neonatal cerebral blood flow velocity or
      resistance, but was associated with decreased (p <.05) perfusion pressure and
      blood flow in the anterior cerebral artery and internal carotid artery during the
      first day of life. Systolic blood pressure and pulse pressure were also lower (p
      <.05) during the whole study period in the MgSO4-exposed infants when compared
      with the controls. Maternal ritodrine treatment, on the other hand, had no
      consistent effects on either neonatal cerebral or systemic hemodynamics.
      CONCLUSIONS: Our data indicate that maternal MgSO4 treatment, in contrast to
      antenatal ritodrine, is associated with lowered cerebral perfusion in preterm
      infants on the first day of life.

PMID- 11445709
TI  - Induced abdominal compartment syndrome increases intracranial pressure in
      neurotrauma patients: a prospective study.
AB  - OBJECTIVE: To evaluate the effect of a stepwise increase in intra-abdominal
      pressure (IAP) on intracranial pressure (ICP) and to further define the pressure
      transmission characteristics of different body compartments. DESIGN: A
      prospective, nonrandomized study. SETTING: A multidisciplinary intensive care
      unit at a university medical center. PATIENTS: Fifteen patients with moderate-to
      severe head injury. INTERVENTIONS: All patients were studied after the initial
      stabilization and resolution of intracranial hypertension. Measurements were
      carried out before and 20 mins after IAP was increased by positioning a soft, 15
      L water bag on the patient's abdomen. MEASUREMENTS AND MAIN RESULTS: Placing
      weights upon the abdomen generated a significant increase in IAP, which rose from
      4.7 +/- 2.9 to 15.5 +/- 4.1 mm Hg (p <.001). The rise in IAP caused concomitant
      and rapid increases in central venous pressure (from 6.2 +/- 2.4 to 10.4 +/- 2.9
      mm Hg; p <.001), internal jugular pressure (from 11.9 +/- 3.2 to 14.3 +/- 2.4 mm
      Hg; p <.001), and ICP (from 12.0 +/- 4.2 to 15.5 +/- 4.4 mm Hg; p <.001).
      Thoracic transmural pressure, calculated as the difference between central venous
      pressure and esophageal pressure, remained constant during the protocol.
      Respiratory system compliance decreased from 58.9 +/- 9.8 to 44.9 +/- 9.4 mL/cm
      H2O (p <.001) in all patients because of decreased chest wall compliance. The
      mean arterial pressure increased from 94 +/- 11 to 100 +/- 13 mm Hg (p <.01),
      which allowed the maintenance of a stable cerebral perfusion pressure (82.4 +/-
      10.3 vs. 84.7 +/- 11.5 mm Hg; p = NS) despite the ICP increase. CONCLUSIONS:
      Increased IAP causes a significant rise in ICP in head trauma patients. This
      effect seems to be the result of an increase in intrathoracic pressure, which
      causes a functional obstruction to cerebral venous outflow. Routine assessment of
      IAP may help clinicians to identify remediable causes of increased ICP. Caution
      should be used when applying laparoscopic techniques in neurotrauma patients.

PMID- 11445711
TI  - Severe sepsis-national estimates.

PMID- 11445712
TI  - Hospital-acquired pneumonia and de-escalation of antimicrobial treatment.

PMID- 11445713
TI  - Fat versus carbohydrate feeding in the critically ill.

PMID- 11445714
TI  - The diaphragm, the magnet, and the critically ill: stimulating perspectives.

PMID- 11445715
TI  - Tissue oxygenation and sepsis.

PMID- 11445716
TI  - Parents should not be excluded from decisions to forgo life-sustaining
      treatments!

PMID- 11445717
TI  - Assessment of delirium: another step forward.

PMID- 11445718
TI  - On the importance of sympathovagal balance.

PMID- 11445719
TI  - Does burn injury affect pulmonary surfactant metabolism?

PMID- 11445720
TI  - Hemofiltration in sepsis: additional supportive evidence.

PMID- 11445721
TI  - Abdominal compartment syndrome in the head-injured patient.

PMID- 11445722
TI  - Hypertonic saline in severe pediatric head injury.

PMID- 11445725
TI  - Sepsis and evolution of the innate immune response.
AB  - OBJECTIVE: To review the role of the Toll-like receptors (TLR) as the principal
      sensors used by the innate immune system in the context of the pathologic
      processes underlying sepsis and septic shock. DATA SOURCES: Literature review.
      DATA SUMMARY: Through the Toll-like receptors, macrophages and other defensive
      cells "see" endotoxin (TLR4), peptidoglycan (TLR2), and bacterial DNA (TLR9).
      Representatives of the family predated the divergence of plants and animals and,
      at that time, had already acquired a defensive function. The strengths and
      liabilities of the innate immune system, which defends against infection and
      which also may cause shock and death, are rooted in its ancient origins. In the
      current era of shock research, the nature of the signals that Toll-like receptors
      transduce and the effects of genetic variation on microbial sensing are two major
      challenges.

PMID- 11445726
TI  - New therapeutic targets revealed through investigations of innate immunity.
AB  - OBJECTIVE: This review describes efforts to define new therapeutic targets by
      utilizing information derived from studies of the innate immune response to
      infection. These targets will provide new means to design novel therapeutics for
      the treatment of human disease caused by dysregulation of the innate immune
      response. DATA SOURCES AND ANALYSIS: The results were derived from model systems
      that reflect the cellular changes accompanying activation of the innate immune
      system. These model systems include the use of a rabbit model of endotoxin shock
      that requires multiple exposures to lipopolysaccharide to induce severe
      pathophysiological changes that result in death. The cellular systems range from
      primary explants of myeloid lineage cells to stably transfected lines bearing key
      receptors of the innate immune system, the latter of which includes the Toll-like
      receptors and CD14. Studies in animal models include blocking monoclonal
      antibodies to rabbit CD14 and rabbit tumor necrosis factor-alpha. Cellular
      studies use measurements of cell activation as defined by activation of nuclear
      factor-kappaB, MAP kinase, and gene expression. In some studies, direct
      measurements of secreted cytokine levels were performed. Standard approaches to
      data analysis have been used. CONCLUSIONS: Evidence demonstrates the utility of
      anti-CD14 monoclonal antibody therapy in septic shock and the potential value of
      targeting intracellular kinases to modulate harmful cellular responses during
      sepsis. The key element to each of these approaches is to blunt, but not
      eliminate, the dysregulated inflammatory response that may occur in sepsis.

PMID- 11445727
TI  - Macrophage migration inhibitory factor and innate immune responses to bacterial
      infections.
AB  - OBJECTIVES: To review the role of macrophage migration inhibitory factor (MIF) in
      host responses to infection and to explore the potential of MIF as a novel target
      for therapeutic intervention in patients with severe sepsis and septic shock.
      DATA SOURCES: Published articles on the role of MIF in innate immune responses
      against microbial pathogens. DATA SUMMARY: MIF has emerged recently as an
      important effector molecule of the innate immune system. MIF is expressed
      constitutively by monocytes/macrophages, T cells, B cells, endocrine cells, and
      epithelial cells. Microbial toxins and cytokines are powerful inducers of MIF
      release by immune cells. MIF expression is up-regulated during the course of
      inflammatory and infectious diseases and was found to play an important role in
      the pathogenesis of sepsis and septic shock. CONCLUSION: Given the role of MIF in
      innate immune responses against microbial pathogens and in the regulation of
      inflammatory responses, modulation of MIF production or neutralization of its
      activity may offer new therapeutic options for the management of patients with
      sepsis.

PMID- 11445728
TI  - Role of Toll-like receptors in inflammatory response in macrophages.
AB  - The innate immune response is the first line of defense against infectious
      disease. It is vital that the host detect the pathogen and rapidly mount a
      defense. The Toll-like family of receptors have evolved to detect conserved
      patterns on pathogens. When stimulated, these receptors activate the inflammatory
      response.

PMID- 11445729
TI  - Clinical expert round table discussion (session 1) at the Margaux Conference on
      Critical Illness: innate immunity: host recognition of and sensitivity to
      bacterial components.

PMID- 11445730
TI  - The endothelium in sepsis: source of and a target for inflammation.
AB  - OBJECTIVE: To discuss a possible role of the endothelium in sepsis. DATA SOURCES:
      Studies published in biomedical journals and our own experimental results. STUDY
      SELECTION: Studies on endothelial mechanisms in the context of sepsis. DATA
      EXTRACTION AND SYNTHESIS: Changes in endothelial cells on activation by
      inflammatory stimuli are reviewed briefly; potential mechanisms that lead to
      endothelial damage during sepsis are discussed. CONCLUSIONS: The endothelium is a
      key organ involved in the pathogenesis of sepsis. Dysfunction of or injury to the
      endothelium may be involved in the pathogenesis of multiple organ failure and
      should be discriminated from activation resulting from stimulation with
      inflammatory stimuli. Identification of the molecular mechanisms that contribute
      to endothelial dysfunction or damage is likely to provide novel targets for the
      treatment of sepsis.

PMID- 11445731
TI  - Vascular bed-specific hemostasis: role of endothelium in sepsis pathogenesis.
AB  - OBJECTIVES: To examine the role of vascular bed-specific pathways in determining
      the hemostatic phenotype in sepsis. DATA SOURCES/STUDY SELECTION: Published
      research and review articles related to hemostasis and endothelial cell biology.
      DATA EXTRACTION AND SYNTHESIS: The results of published studies have been used to
      generate a hypothesis of vascular bed-specific hemostasis in sepsis. CONCLUSIONS:
      In sepsis, coagulation is initiated by the extrinsic pathway and is amplified
      through the intrinsic pathway. In addition, the body's natural anticoagulant
      mechanisms are significantly dampened. Together, these changes result in a net
      imbalance of hemostasis. The nature of this imbalance varies from one vascular
      bed to the next according to the local set point of the endothelium. These
      concepts lay an important foundation for understanding the pathophysiology of
      sepsis.

PMID- 11445732
TI  - Endothelial cell dysfunction and coagulation.
AB  - OBJECTIVES: a) To review endothelial properties and to establish how these
      unperturbed properties contribute to the maintenance of endothelium anticoagulant
      activity; b) to better understand the relative contributions of endothelial cells
      and monocytes in sepsis-induced altered coagulation. DATA SOURCES: A summary of
      published literature from MEDLINE search files and other original articles and
      reviews published on endothelial cell and monocyte functions and modifications
      owing to sepsis. DATA EXTRACTION AND SYNTHESIS: Unperturbed endothelial cells
      provide anticoagulant properties; exposure to inflammatory and/or septic stimuli
      can rapidly lead to procoagulant behavior. Sepsis alters endothelial cell surface
      and induces tissue factor synthesis at the endothelial and subendothelial levels.
      During endotoxemia, endothelial cells generate adhesion molecules that bind
      leukocytes and monocytes, increasing local procoagulant reactions. Tissue factor
      expression is also increased at the level of the monocyte; the relative
      importance of endothelial injury and monocyte activation in coagulation disorders
      was recently assessed. Endothelium protection before induction of septic shock
      was not associated with any reduction in monocyte tissue factor expression,
      suggesting that altered coagulation was present despite normal endothelial cell
      function. On the other hand, decreased monocyte tissue factor expression was
      associated with a marked reduction in endothelial injury, increased endothelium
      derived relaxation, and improved survival rate in treated animals. CONCLUSIONS:
      This review suggests that monocyte activation and tissue factor expression may be
      of paramount importance in sepsis-associated injuries and that coagulation
      activation may contribute to the endothelial cell injury observed during sepsis.
      Endothelial injury, in turn, exacerbates sepsis-induced coagulation
      abnormalities.

PMID- 11445733
TI  - Hepatic response to sepsis: interaction between coagulation and inflammatory
      processes.
AB  - OBJECTIVES: a) To review the hepatic response to sepsis and to establish how this
      response contributes to coagulation and inflammatory processes; b) to review the
      physiologic and biochemical mechanisms that suggest hepatic dysfunction may occur
      during sepsis, enhance procoagulant and proinflammatory activities, and
      participate in the potential evolution to multiple organ dysfunction syndrome.
      DATA SOURCES: A summary of published medical literature from MEDLINE search files
      and published reviews on liver function in experimental and human sepsis. DATA
      SUMMARY: In sepsis, the liver plays a major role in host defense mechanisms.
      Kupffer cells are responsible for bacterial scavenging, bacterial products
      inactivation, and inflammatory mediators clearance and production. Hepatocytes,
      via receptors for many proinflammatory cytokines, modify their metabolic pathway
      toward gluconeogenesis, amino-acid uptake, and increased synthesis of coagulant
      and complement factors and protease inhibitors. The acute-phase protein (APP)
      response also contributes to the procoagulant state, especially by enhancing the
      inhibition of protein C (alpha1-antitrypsin and alpha2-macroglobulin) and by
      decreasing liver synthesis of protein C and antithrombin (negative APPs).
      Elevated C-reactive protein levels (positive APPs) promote the expression of
      tissue factor by mononuclear cells. Increased liver production of thrombin
      activatable fibrinolytic inhibitor (positive APPs) enhances fibrinolysis
      inhibition. Conversely, such hepatic inflammatory and coagulation processes in
      sepsis may alter the function of this organ. Indeed, the liver can be injured by
      activated Kupffer cells that release chemokines, attract blood neutrophils into
      the liver, and activate them. Neutrophils up-regulate their surface adhesion
      molecules, tissue factor, and Kupffer cells, whereas tissue factor pathway
      inhibitor and thrombomodulin are almost undetectable in endothelial cells. This
      may lead to microcirculatory disturbances, fibrin deposition, hepatocyte injury,
      endotoxin and bacteria spillover, and multiple organ failure. CONCLUSIONS: In
      sepsis, the liver participates in host defense and tissue repair through hepatic
      cell cross-talk that controls most of the coagulation and inflammatory processes.
      When this control is not adequate, a secondary hepatic dysfunction may occur and
      may sometimes lead to bacterial products spillover, enhanced procoagulant and
      inflammatory processes, and in turn, multiple organ failure and death.

PMID- 11445734
TI  - Protein C anticoagulant pathway and its role in controlling microvascular
      thrombosis and inflammation.
AB  - OBJECTIVE: To review the physiologic and biochemical mechanisms that suggest that
      protein C and activated protein C (APC) have unique properties that make them
      good candidates for the treatment of microvascular thrombosis, disseminated
      intravascular coagulation, and sepsis. DATA SOURCES: A summary of published
      medical literature from MEDLINE search files and published reviews on protein C
      physiology, biochemical properties, and activity in experimental and human
      sepsis. DATA SUMMARY: Protein C is critical to the regulation of microvascular
      coagulation, as seen most clearly in humans born with congenital deficiency of
      protein C, who develop neonatal purpura fulminans. Protein C supplementation
      reverses the lesion formation. In primate models of sepsis, APC blocks
      disseminated intravascular coagulation initiated by Escherichia coli infusion,
      and inhibition of APC function exacerbates both the coagulant and inflammatory
      responses of the animals to sublethal levels of E. coli. In vitro experiments
      have shown that APC can inhibit neutrophil binding to selectins: Endothelial cell
      protein C receptor, a protein C/APC binding receptor, can bind to proteinase 3
      bound to Mac-1 on leukocytes, potentially blocking tight leukocyte adhesion; and
      APC can inhibit tumor necrosis factor-alpha secretion by monocytes and other cell
      lines by interfering with nuclear factor-kappaB nuclear translocation. By
      blocking nuclear factor-kappaB nuclear translocation, cytokine- and endotoxin
      mediated adhesion molecule up-regulation is decreased. These properties of APC
      are consistent with a large number of animal studies demonstrating that APC can
      diminish complications of crush injury and leukocyte damage to lung and other
      tissues in response to sepsis and decrease the inflammatory response. The animal
      studies are consistent with the phase 2 studies reported on APC use in the
      treatment of human sepsis. CONCLUSIONS: The protein C pathway is uniquely poised
      to interfere with the microvascular coagulation and inflammation that follows
      challenge with endotoxin. By limiting leukocyte activation, cytokine elaboration,
      and microvascular coagulation, APC has been shown to prevent organ damage in
      experimental models of sepsis. These results are consistent with the initial
      phase 2 reports of APC therapy in human sepsis suggesting a clinical benefit and
      demonstrating anti-inflammatory activity with several reports of apparent protein
      C effectiveness in severe sepsis, especially meningococcemia.

PMID- 11445735
TI  - Recombinant human activated protein C: a system modulator of vascular function
      for treatment of severe sepsis.
AB  - OBJECTIVE: To review the mechanisms of action and rationale for the use of
      recombinant human activated protein C in the treatment of severe sepsis.
      Specifically, we focus on the mechanisms of action in the protein C pathway that
      converge to modulate the pathophysiology of severe inflammatory disease and
      sepsis. This analysis includes a discussion of the role of activated protein C in
      directly modulating cell system biology, independent of antithrombotic activity.
      DATA SOURCES/STUDY SELECTION: Published research and review articles relating to
      the protein C pathway, recombinant human protein C, and the role of protein C in
      sepsis. Data were also derived from broad gene profiling in model systems of
      endothelial dysfunction. DATA EXTRACTION AND SYNTHESIS: Relevant studies were
      included to support discussion of the unique mechanistic aspect of protein C and
      its role in the pathogenesis of severe sepsis. We discuss the potential of
      activated protein C as a unique system modulator for the treatment of severe
      sepsis and other systemic inflammatory responses that result in microvascular
      coagulopathy, endothelial dysfunction, and vascular bed failure. CONCLUSIONS: The
      protein C pathway plays a unique role in modulating vascular function. As an
      antithrombotic/profibrinolytic agent, it plays a clear role in maintaining
      vascular patency. Moreover, it has anti-inflammatory properties and appears to
      play a unique role as an antiapoptotic and endothelial cell survival factor. In
      states of systemic inflammatory activation, loss of protein C due to consumptive
      processes results in a compromised ability to modulate coagulation as well as
      inflammatory and cell survival functions. This compromise leads to vascular
      dysfunction, end-organ failure, and death. Replacement with recombinant human
      activated protein C offers a system-modulating approach to improved outcome.

PMID- 11445736
TI  - Coagulation in severe sepsis: a central role for thrombomodulin and activated
      protein C.
AB  - OBJECTIVES: To review the mechanisms that cause coagulation abnormalities in
      sepsis, focusing on the interaction between the vascular endothelium and the
      circulating coagulation factors, particularly the role of the protein C pathway
      and thrombomodulin. DATA SOURCES/STUDY SELECTION: Published research abstracts
      and review articles on the experimental and clinical investigation of the
      pathophysiology of disseminated intravascular coagulation in sepsis. DATA
      EXTRACTION AND SYNTHESIS: The data provide increasing evidence that the
      coagulopathy seen in sepsis is a result of a complex imbalance of pro- and
      anticoagulant pathways. Whereas previous research has largely studied events in
      the plasma, it is now apparent that reactions on cell surfaces such as the
      vascular endothelium are important in the control of the regulatory pathways.
      CONCLUSIONS: The plasma components of the protein C pathway are down-regulated in
      sepsis. Decreased thrombomodulin expression may cause defective function of the
      endothelial component of this pathway in septic patients. Treatments must be
      designed to overcome any functional defect.

PMID- 11445737
TI  - Activated protein C versus protein C in severe sepsis.
AB  - OBJECTIVE: To delineate critical differences between activated protein C (APC)
      and its precursor, protein C, with regard to plasma levels in health and in
      severe sepsis, and to discuss the implications of these differences as they
      relate to treatment strategies in patients with severe sepsis. DATA SOURCE/STUDY
      SELECTION: Published literature including abstracts, manuscripts, and review
      articles reporting studies in both experimental animal models and humans that
      provide an understanding of the relationship and the critical differences between
      circulating levels of APC and protein C. DATA EXTRACTION AND SYNTHESIS: The
      protein C pathway represents one of the major regulatory systems of hemostasis,
      exhibiting antithrombotic, profibrinolytic and anti-inflammatory properties. This
      pathway also plays a critical role in the pathophysiology of severe sepsis.
      Central to this pathway is the vitamin K-dependent serine protease, APC, and its
      precursor, protein C. The conversion of protein C to APC is dependent on the
      complex of thrombin and thrombomodulin, an integral endothelial surface receptor.
      The conversion of protein C to APC is further augmented by another endothelial
      surface protein, the endothelial protein C receptor. There are limited published
      data on APC levels in health and disease, probably due to the complexity of the
      assay methodology for measuring APC and the absence of commercially available
      diagnostic kits. In animals and humans with normal functioning endothelium,
      circulating levels of APC (1-3 ng/mL) are positively correlated with protein C
      (4000-5000 ng/mL) concentration and the amount of thrombin generated. In patients
      with severe sepsis, there is a generalized endothelial dysfunction, contributing
      to multiple organ failure with increased morbidity and mortality. Persistently
      low protein C levels are related to poor prognosis. Key to understanding the
      treatment strategy with APC or protein C is knowledge of the functional status of
      the endothelium and, specifically, whether the microvasculature in patients with
      severe sepsis can support the conversion of protein C to APC. To date, only APC
      (drotrecogin alfa [activated]) has been shown to reduce mortality in severe
      sepsis in a large, phase 3, placebo-controlled, double-blind international trial.
      In contrast, no data, other than open-label case studies, are available for
      evaluation of the effects of protein C in the treatment of severe sepsis.
      CONCLUSION: The limited data available indicate that lower levels of protein C in
      sepsis occur in the absence of appreciable conversion to APC. These observations
      indicate that treatment with APC may be more efficacious than protein C in severe
      sepsis, where generalized endothelial dysfunction may impair conversion of
      protein C to APC. Additional research is required to confirm these observations.

PMID- 11445738
TI  - Clinical expert round table discussion (session 3) at the Margaux Conference on
      Critical Illness: the role of activated protein C in severe sepsis.

PMID- 11445739
TI  - Staging of the pathophysiologic responses of the primate microvasculature to
      Escherichia coli and endotoxin: examination of the elements of the compensated
      response and their links to the corresponding uncompensated lethal variants.
AB  - OBJECTIVE: Review of primate studies of Escherichia coli sepsis and endotoxemia
      with a reexamination of the rationale for diagnosis and treatment of these
      multistage disorders. SETTING: Animal research and intensive care units in a
      university medical school. SUBJECTS: Cyanocephalus baboons (E. coli) and normal
      human subjects (endotoxin). INTERVENTIONS: Baboon studies: anti-tissue factor,
      protein C, endothelial protein C receptor, and anti-tumor necrosis factor
      antibodies, and active site inhibited factor recombinant VIIa and factor Xa.
      RESULTS AND CONCLUSIONS: This review concerns the primate microvascular
      endothelial response to inflammatory and hemostatic stress. Studies of the impact
      of inflammatory and hemostatic stress on this microvasculature have fallen into
      four categories. First, studies of pure hemostatic stress using factor Xa
      phospholipid vesicles showed that blockade of protein C as well as protein C plus
      tissue plasminogen activator produced a severe but transient consumptive and a
      lethal thrombotic coagulopathy, respectively. These studies showed that the
      protein C and fibrinolytic systems can work in tandem to regulate even a severe
      response if the endothelium is not rendered dysfunctional by metabolic or
      inflammatory factors. Second, studies of compensated (nonlethal) inflammatory
      stress using E. coli or endotoxin in baboon and human subjects showed that even
      under minimal stress in which there is no evidence of overt disseminated
      intravascular coagulation, injury of the endothelium and activation of
      neutrophils and hemostatic factors are closely associated. This showed that
      molecular markers of hemostatic activity could be used to detect microvascular
      endothelial stress (nonovert disseminated intravascular coagulation) in patients
      who are compensated but at risk. These studies also showed that the compensated
      response to inflammatory stress could exhibit two stages, each with its unique
      inflammatory and hemostatic response signature. The first is driven by vasoactive
      peptides, cytokines, and thrombin, followed 12 to 14 hrs later by a second stage
      driven by C-reactive protein/complement complexes, tissue factor, and plasminogen
      activator inhibitor 1 secondary to oxidative stress after reperfusion. Third,
      studies of uncompensated (lethal) inflammatory stress using E. coli showed that
      irreversible thrombosis of the microvasculature was not a link in the lethal
      chain of events even though inhibition of components of the protein C network
      (protein C and endothelial protein C receptor) converted compensated responses to
      sublethal E. coli into uncompensated lethal responses. Fourth, these studies also
      showed that there were variants of the lethal response ranging from capillary
      leak and shock to recurrent sustained inflammatory disorders. We believe that
      each of these variants arises from their sublethal counterparts, depending on
      underlying or modulating host factors operating at the time of challenge. Such
      underlying conditions range from preexisting microvascular ischemia, reperfusion,
      and oxidative stress to alteration or reprogramming of monocyte/macrophage
      responses (tolerance to hyperresponsiveness). Characterization of these
      underlying conditions in patients who are at risk should aid in identifying and
      optimizing management of these variants.

PMID- 11445740
TI  - Rationale for restoration of physiological anticoagulant pathways in patients
      with sepsis and disseminated intravascular coagulation.
AB  - OBJECTIVE: In the pathogenesis of disseminated intravascular coagulation,
      dysfunctional natural anticoagulant pathways appear to play a pivotal role. In
      this article, we will address the mechanisms that contribute to this defect in
      the regulation of coagulation activation. Furthermore, we will explore the
      experimental and clinical evidence that restoration of these anticoagulant
      pathways results in clinical improvement. DATA SOURCES: We have searched and
      reviewed published articles on experimental studies of disseminated intravascular
      coagulation models in animals and clinical studies in patients with disseminated
      intravascular coagulation. DATA SYNTHESIS: All three major anticoagulant
      pathways, that is, the antithrombin pathway, the protein C system, and tissue
      factor pathway inhibitor, are defective in sepsis and disseminated intravascular
      coagulation. Several mechanisms contribute to this defect. Restoration of these
      pathways, in principle, by administration of coagulation inhibitor concentrates
      or recombinant anticoagulant factors, appears to ameliorate the coagulation
      disorder and, more important, result in improvement of clinically relevant
      outcomes, such as a reduction of organ failure and mortality. CONCLUSIONS:
      Restoration of disrupted physiologic anticoagulant pathways in disseminated
      intravascular coagulation is not only a logical point of impact in patients with
      sepsis and an activated coagulation system, but also is associated with an
      improved outcome in experimental and (initial) clinical studies.

PMID- 11445741
TI  - Microvascular coagulopathy and disseminated intravascular coagulation.
AB  - OBJECTIVE: To review the dual characteristics of disseminated intravascular
      coagulation (DIC), as both a contributor to multiple organ failure as well as a
      symptom of severe underlying disease associated with systemic vascular changes.
      DATA SOURCES: Published literature data and unpublished results from the authors.
      DATA SUMMARY: Clinical and experimental studies strongly suggest that DIC
      contributes to multiple organ failure and death in patients with severe systemic
      disorders such as sepsis. DIC is evoked by systemic cytokine activity, and the
      inflammatory response aggravates vascular permeability, inflammation, and cell
      damage in tissues. In addition to intravascular fibrin formation, thrombin and
      fibrin generation in tissues is also an important aspect of DIC. An example of
      DIC at the organ level is adult respiratory distress syndrome, where fibrin in
      the lung is a characteristic feature. Intravascular fibrin formation and
      occlusion may elicit a hypoxic response with induction of hypoxia related
      transcription factors. The resulting ischemic preconditioning may offer
      protective effects to the involved organ(s). CONCLUSIONS: Overall, the beneficial
      or harmful effects of activated coagulation and fibrin formation for organ
      pathology and recovery from DIC remain to be explored. This may be a critical
      element in the assessment of ischemia-reperfusion effects of specific
      anticoagulant therapy.

PMID- 11445742
TI  - Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction
      syndrome.
AB  - OBJECTIVE: An improved understanding of the mechanisms through which infecting
      pathogens harm the host is leading to new formulations of the concept of sepsis.
      We review the roles of inflammation and coagulation in the pathogenesis of the
      multiple organ dysfunction syndrome, and explore the potential of new therapies
      to restore the fine biological balance between procoagulant and anticoagulant
      mechanisms that are disrupted during the life-threatening processes that lead to
      organ dysfunction. DATA SOURCES: Narrative review of published primary sources in
      the basic and clinical literature. DATA SUMMARY: Traditional models of host
      pathogen interactions ascribe the morbidity of infection to the direct cytotoxic
      effects of micro-organisms on host tissues. However, abundant experimental and
      clinical evidence has revealed that it is the response of the host, rather than
      the trigger that elicited it, that is the more potent determinant of outcome. The
      elucidation of a complex network of host-derived inflammatory mediators raised
      the possibility that targeting these individually could improve patient outcomes,
      and some modest successes with this approach have been achieved. More recently,
      it is becoming evident that the inflammatory response, in turn, mediates its
      deleterious effects by inducing tissue hypoxia, and cellular injury, either
      through tissue necrosis or through the induction of programmed cell death or
      apoptosis. Thus, treatment strategies that target the downstream consequences of
      the activation of inflammation, for example, microvascular coagulation or acute
      adrenal insufficiency, represent the latest, and some of the most promising
      approaches to attenuation of the septic response to improve survival, and
      minimize organ dysfunction. The maladaptive sequelae of systemic inflammation,
      embodied in the concept of the multiple organ dysfunction syndrome, comprise the
      leading obstacle to survival for patients admitted to a contemporary intensive
      care unit. Further insights into this intimidatingly complex process will not
      only provide potent new therapeutic options, but promise to transform critical
      illness from a biological standoff, during which the clinician merely supports
      failing organs, to a disease that can be successfully treated.

PMID- 11445743
TI  - Clinical expert round table discussion (session 4) at the Margaux Conference on
      Critical Illness: sepsis: inflammation disorder, coagulation disorder, or both? A
      challenge for clinicians.

PMID- 11445744
TI  - Epidemiology of sepsis: an update.
AB  - OBJECTIVE: We review the case definition, occurrence, and outcome of sepsis. We
      discuss whether the epidemiology of sepsis has changed over time and discuss
      issues important to our understanding of sepsis. DATA SOURCES: Literature review.
      DATA SUMMARY: Our understanding of the epidemiology of sepsis is hampered by the
      lack of a reliable case definition. Inconsistent application of sepsis definition
      criteria contributes to confusion and variability in the literature. Variability
      in the time course of sepsis also introduces difficulty. The Centers for Disease
      Control estimated an incidence of 73.6 per 100,000 population in 1979, rising to
      175.9 per 100,000 in 1989. However, this study was of septicemia, not severe
      sepsis. There are several hospital-based studies of the occurrence of severe
      sepsis, defined using the American College of Chest Physicians/Society of
      Critical Care Medicine consensus criteria. These studies reported variable
      hospital and intensive care unit (ICU) occurrence rates, ranging from 2% to 11%
      of all hospital or ICU admissions. Most of these data are from academic, tertiary
      care centers, which limits generalizability. More population-based studies are
      required to better delineate the incidence and risk factors of sepsis in the
      general population. Hospital mortality from sepsis has ranged from 25% to 80%
      over the last few decades. Although mortality may be lower in recent years,
      sepsis is clearly still a very serious condition. Achieving a better
      understanding of whether the mortality rate for sepsis is falling, however, is
      confounded by the lack of a uniform definition. Risk factors for adverse outcome
      include the degree of physiologic derangement, organ dysfunction, underlying
      illness, site of infection, and microbiological etiology. We do not know,
      however, the factors that predict response to new therapies. This dilemma has led
      researchers to explore whether markers of the inflammatory cascade might be more
      specific for sepsis, more accurate for risk prediction, or more useful for
      predicting response to therapy. However, there as yet is no equivalent of the CPK
      MB for acute myocardial infarction. Whether we will find such a marker as we
      develop a greater understanding of the genetic control of the inflammatory
      cascade is uncertain but promising. One might assume intuitively that the
      epidemiology of sepsis is changing. For example, the number of patients being
      treated in ICUs has increased over time, the technologies used in the ICU have
      changed, and the choice and the use of antibiotics have changed. Predisposing
      factors, such as chemotherapeutic regimens, have also changed, and there have
      been marked changes in antibiotic resistance. Furthermore, there have been wide
      changes in the microbiological etiologies of diseases such as pneumonia and acute
      exacerbations of chronic bronchitis. However, lacking good case definitions and
      true incidence studies, we can only make inferences about whether the
      epidemiology of sepsis is truly changing. CONCLUSION: Many studies have
      documented many aspects of the epidemiology of sepsis. However, the composite
      picture they provide, although rich in many aspects, remains incomplete and
      emphasizes the heterogeneity of the condition. Unfortunately, few population
      based prospective cohort studies exist that allow us to accurately delineate the
      risk factors for sepsis, its course, and its outcome. To place new information,
      such as the role of genetic predisposition, in the correct context, it is
      essential that such studies be conducted.

PMID- 11445745
TI  - Corticosteroids for septic shock.
AB  - OBJECTIVE: To gather the data to provide a rationale for using replacement
      therapy with hydrocortisone in septic shock patients. DATA SOURCES: The Medline
      and the Cochrane Library databases. STUDY SELECTION: Studies in animals and in
      humans were considered when significant data were available about the mechanisms
      of action of corticosteroids or about their use in severe sepsis. DATA SUMMARY:
      Corticosteroids were the first anti-inflammatory drugs tested in septic patients.
      Randomized trials clearly showed that a short course of a large dose of anti
      inflammatory steroids is ineffective and potentially harmful in patients with
      severe sepsis. Recent demonstrations of altered hypothalamic-pituitary-adrenal
      axis response to septic insult have led to a reappraisal of the use of steroids
      in septic shock. Randomized trials in catecholamine-dependent septic shock
      patients strongly suggest that replacement therapy with hydrocortisone may
      alleviate the symptoms of systemic inflammatory response, reduce the duration of
      shock, and favorably affect survival. CONCLUSIONS: Current evidence that the
      therapeutic interest of replacement therapy with corticosteroids increases
      suggests that low doses of hydrocortisone should be offered to patients with
      catecholamine-dependent septic shock.

PMID- 11445746
TI  - Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and
      lessons learned.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) is an important mediator involved in the
      pathogenesis of sepsis. We review clinical studies investigating the efficacy of
      anti-TNF therapy in decreasing mortality rates in septic patients. DATA SOURCES:
      We conducted a computerized bibliographic search of randomized, clinical,
      multicenter trials studying the effects of anti-TNF therapy in the treatment of
      sepsis. We included all primary studies, reviewed all published meta-analyses,
      and contacted primary investigators of multicenter trials where necessary. DATA
      SYNTHESIS: Almost all randomized studies targeting TNF during sepsis show a
      small, albeit nonsignificant, benefit in decreasing mortality. Strategies using
      monoclonal antibodies are more effective than are strategies using TNF receptor
      proteins. Analysis of randomized multicenter trials shows a small but significant
      benefit with anti-TNF therapeutic strategies. Furthermore, a recent study in 2634
      septic patients using a murine anti-TNF antibody shows a 3.6% significant benefit
      in reducing mortality. CONCLUSIONS: Anti-TNF strategies are only partially
      effective in patients with sepsis. Although individual studies show small,
      nonsignificant benefits, analysis of all trial data as well as data from a recent
      trial in a large population of septic patients show that anti-TNF strategies may
      confer a small survival benefit. Better characterization of patients and a more
      multimodal approach by concomitantly targeting other mediators involved in sepsis
      may be helpful in enlarging the clinical benefit of anti-TNF therapy.

PMID- 11445747
TI  - Tissue factor pathway inhibitor activity in severe sepsis.
AB  - OBJECTIVE: To review the preclinical and clinical evidence that provides the
      therapeutic rationale for recombinant human tissue factor pathway inhibitor
      (rTFPI) as a novel treatment for human sepsis. DATA SOURCES: A summary of
      published English-language literature regarding preclinical studies and limited
      information published about three phase II clinical studies for the evaluation of
      rTFPI safety in sepsis patients. DATA SUMMARY: Tissue factor pathway inhibitor,
      the physiologic inhibitor of the tissue factor pathway, interrupts activation of
      coagulation at multiple steps, including tissue factor VIIa activity, Xa
      activity, prothrombinase complex, and thrombin generation. Recombinant human TFPI
      exhibits anticoagulant and anti-inflammatory activities in animal models and
      humans with sepsis. These activities appear to have an important therapeutic role
      in protecting the microvasculature from injury and preventing multiple organ
      failure in sepsis. CONCLUSIONS: Tissue factor pathway inhibitor is a potent
      inhibitor of clotting in the microvasculature, which is thought to protect organs
      from injury. Recombinant TFPI improved survival of septic animals in multiple
      models. Recent phase II results suggest that rTFPI is well tolerated, and they
      show a trend toward reduction in 28-day all-cause mortality in rTFPI-treated
      patients; in addition, rTFPI demonstrated significant reduction in thrombin
      generation. These results suggest that a powered study is indicated to further
      evaluate rTFPI utility for the adjunctive management of severe sepsis.

PMID- 11445748
TI  - Bactericidal/permeability-increasing protein--lessons learned from the phase III,
      randomized, clinical trial of rBPI21 for adjunctive treatment of children with
      severe meningococcemia.
AB  - OBJECTIVES: To review the scientific rationale for the clinical use of
      recombinant bactericidal permeability-increasing protein (rBPI21) and to discuss
      the results, implications, and lessons learned during the clinical development of
      rBPI21 for adjunctive treatment of children with severe meningococcemia. DATA
      SOURCES: The published medical literature. STUDY SELECTION: Of the phase I/II and
      phase III trials in humans, preclinical experimental studies were selected. Data
      from these sources are presented in the context of the authors' experiences as
      principal investigators in the phase I/II and/or phase III clinical trials. DATA
      EXTRACTION AND DATA SYNTHESIS: Bactericidal permeability-increasing protein and N
      terminal fragments of bactericidal permeability-increasing protein, such as
      rBPI21, bind and neutralize endotoxin and are potently bactericidal against both
      smooth and rough forms of Gram-negative bacteria, including Neisseria
      meningitidis. Based on these properties and compelling preclinical data
      indicating that administration of rBPI21 reduced mortality in several models of
      sepsis, we initiated clinical trials by using rBPI21 as adjunctive therapy for
      children with severe meningococcemia. Data from the phase III, randomized,
      placebo-controlled trial indicate that rBPI21 reduces clinically significant
      morbidities and improves the functional outcome of children with severe
      meningococcemia. No statistically significant benefit in mortality was
      demonstrated; however, because of the rare incidence of disease and the rapidity
      of death in this study, the trial was substantially underpowered to detect a
      statistically significant mortality advantage. Before the completion of the
      trial, the probability that the study might have been underpowered to detect a
      significant reduction in mortality was recognized. An attempt at selecting a
      previously unvalidated composite end point to increase the meaningful event rate
      for the primary end point proved unsuccessful. Significant improvements were seen
      in other prospectively defined outcome variables that suggest an overall
      substantial benefit of therapy with rBPI21 in children with severe
      meningococcemia. CONCLUSIONS: As the largest therapeutic trial conducted in
      pediatric critical care, the phase III trial of rBPI21 demonstrates important
      principles that can influence the design of future trials targeting rare, life
      threatening diseases.

PMID- 11445749
TI  - Clinical expert round table discussion (session 5) at the Margaux Conference on
      Critical Illness: outcomes of clinical trials in sepsis: lessons learned.

PMID- 11445750
TI  - Proceedings of the Second Margaux Conference on Critical Illness Sepsis:
      Interface between Inflammation, Coagulation, and the Endothelium. Margaux,
      France, November 8-12, 2000.

PMID- 11445751
TI  - Anterior positioning of tibia during motion after anterior cruciate ligament
      injury.
AB  - PURPOSE: The purpose of this study was to describe the sagittal tibial
      translation and EMG activity of muscles v. medialis and lateralis, gastrocnemius,
      and hamstrings, during common locomotion, in patients with an anterior cruciate
      ligament deficiency (ACL-def) and uninjured controls. METHODS: In 12 ACL-def
      patients and 17 controls, sagittal tibial translation was registered with the CA
      4000 electrogoniometer during level walking, cutting, and stair walking. Tibial
      position at each flexion angle was expressed relative to the femuro-tibial
      position at passive knee extension. EMG activity, measured with ME-4000, was
      normalized to the individual maximum isometric voluntary contraction for each
      muscle. RESULTS: During the weight-bearing phase of motion, the tibia was
      anteriorly positioned in all legs. In the injured leg, the tibia translated more
      rapidly to an anterior position that was maintained for a longer time during the
      gait cycle. In the noninjured knees, motions with increased load lead to an
      increased anterior tibial translation in contrast to the injured knees, where the
      maximum displacement was already reached during level walking. The quadriceps and
      gastrocnemius muscles were simultaneously active during stance phase. Hamstrings
      were mainly active when the knee was close to extension and translation increased
      in spite of this activity. CONCLUSIONS: The mechanism of the anterior positioning
      of tibia is qualitatively similar in the normal and the injured knee, but that
      position is obtained much further forward in the ACL deficient knee. Quadriceps
      and gastrocnemius muscles seem to work synergistically to stabilize the knee by
      maintaining the anterior position of tibia during weight-bearing motion. The role
      of hamstrings to restrict anterior translation is questioned.

PMID- 11445752
TI  - Effects of position and speed on joint torques and knee shear after ACL injury.
AB  - PURPOSE: The purpose of this study was to assess the effect of joint position and
      movement speed on hip (HT) and knee (KT) extensor torque, HT/KT ratio (HKR), and
      anterior tibial shear (S) in presurgical-ACL deficient (PRE; N = 15), post-ACL
      reconstructed (POST; N = 15), and uninjured controls (CON; N = 15). METHODS:
      Measurements were recorded on a semirecumbent variable resistance, closed-chain
      dynamometer. Tests were conducted at 1 and 1.5 Hz and maximum speed at 33% and
      50% 1RM. HT, KT, and S were recorded during the extension phase of the cycle (85
      degrees -25 degrees of knee flexion). RESULTS: KT was greatest when the knee was
      more flexed, whereas HT dominated when it was more extended. This suggests that
      the hamstrings, as a component of the hip extensors, may generate considerable
      propulsive force during knee extension, which may help counter anterior tibial
      shear. S increased whereas KT decreased, suggesting that the quadriceps continue
      to generate shear force despite the decreasing mechanical advantage producing KT.
      Increasing knee extension speed significantly decreased S in the POST and CON
      groups. The correlations between KT and S changed from significantly negative to
      significantly positive as the knee extended from 85 degrees to 25 degrees in the
      POST and CON groups. This may be related to the orientation of the patellar
      tendon, relative to the tibial longitudinal axis that shifts from a posterior to
      anterior direction, as the knee extends. CONCLUSIONS: Joint position and movement
      speeds affect the magnitude of hip and knee torques and anterior tibial shear.
      Reducing the magnitude of S during heavy loads may be a normal phenomenon, and
      POST surgical subjects may retain or regain this function by 1 yr after surgery.

PMID- 11445753
TI  - Correlates of compliance in a randomized exercise trial in myocardial infarction
      patients.
AB  - PURPOSE: Exercise-based rehabilitation programs have been associated with
      decreased morbidity and mortality after myocardial infarction. Unfortunately,
      attendance is often poor, and information is limited regarding predictors of long
      term compliance to such programs. This study examined factors associated with
      exercise session compliance over 3 yr in male myocardial infarction (MI)
      survivors. METHODS: Subjects were participants in the National Exercise and Heart
      Disease Project, a 3-yr (1976-1979) multicenter, randomized clinical trial (N =
      651); 308 men, 30-64 yr of age, were randomized to the exercise treatment group,
      that met three times/week throughout the study. Compliance was defined as the
      number of sessions attended/number of sessions conducted. Patient characteristics
      at enrollment were considered as possible predictors of compliance. RESULTS:
      Compliance decreased as time since enrollment increased with the largest decrease
      observed after the first 8 wk. Compliance correlated positively with exercise
      test measures [last completed stage (r = 0.17, P < 0.01), peak heart rate (r =
      0.11, P = 0.06)], high density lipoprotein (HDL) cholesterol (r = 0.15, P =
      0.10), age (r = 0.11, P = 0.07), and inversely with body mass index (r = -0.19, P
      = 0.001), sum of three skinfolds (r = -0.15, P < 0.01), total cholesterol (r = 
      0.18, P < 0.01), triglycerides (r = -0.16, P < 0.01), and depression (r = -0.09,
      P < 0.11). Current smokers were less compliant than former and nonsmokers (r = 
      0.21, P < 0.001). The correlations with last completed stage, BMI, skinfolds,
      total cholesterol, and smoking status were statistically significant. The model
      explained 22.2% of the variance in compliance (r2 = 0.222). Baseline work
      capacity was among the most consistent predictors of early and late compliance.
      CONCLUSION: Compliance decreased over time. Men already at high risk for repeat
      events due to elevated risk factors were less compliant. These findings have
      important clinical implications regarding screening, intervention, and
      participation in potential cardiac rehabilitation program dropouts.

PMID- 11445754
TI  - Predictors of isotonic exercise in patients with heart failure.
AB  - PURPOSE: Study aims were to determine the predictors of isotonic resistance
      exercise performance in patients with advanced heart failure and to compare the
      preexercise values of patients who experienced a negative physiologic response to
      resistance exercise with those who had minimal or no response. METHODS: A
      correlational design was used. After pharmacologic left ventricular unloading
      therapy using a pulmonary artery catheter, 34 patients with advanced heart
      failure performed graduated isotonic weight-lifting exercises. Measurements were
      made of hemodynamics and rating of perceived exertion after each test. RESULTS:
      The following variables, measured at baseline, were significantly correlated with
      the amount of weight patients were able to lift: rating of perceived exertion
      (RPE; r = -0.42, P = 0.014); diastolic blood pressure (DBP; r = 0.49, P = 0.03);
      systolic blood pressure (SBP; r = 0.40, P = 0.017); pulmonary capillary wedge
      pressure (PCWP; r = 0.39, P = 0.026); and right atrial pressure (RAP; r = 0.35, P
      = 0.041). Multiple regression analysis, using a stepwise procedure, showed that
      47% of the variance in exercise performance was explained by DBP, RPE, and PCWP.
      There were no significant differences in baseline hemodynamics, ejection
      fraction, or age between the group of patients who had a negative hemodynamic
      response at peak exercise and the group of patients who had minimal or no
      response. CONCLUSIONS: Resting PCWP, DBP, and RPE can provide important
      information to help clinicians predict isotonic resistance exercise performance
      in patients with advanced heart failure. However, those patients who have a
      negative response to this type of exercise cannot be distinguished at baseline by
      clinical characteristics or age.

PMID- 11445755
TI  - Muscle glycogen supercompensation is enhanced by prior creatine supplementation.
AB  - PURPOSE: Recently, it was shown that glycogen supercompensation tended (P = 0.06)
      to be greater if creatine and glycogen were loaded simultaneously. Because the
      authors suggested that creatine loading increased cell volumes and, therefore,
      enhanced glycogen supercompensation, we decided to determine whether an enhanced
      glycogen supercompensation could be realized if the glycogen loading protocol was
      preceded by a 5-d creatine load. METHODS: Twelve men (19-28 yr) performed two
      standard glycogen loading protocols interspersed with a standard creatine load of
      20 g.d(-1) for 5 d. The vastus lateralis muscle was biopsied before and after
      each loading protocol. RESULTS: The initial glycogen loading protocol showed a
      significant 4% increase (P < 0.05) in muscle glycogen (Delta upward arrow 164 +/-
      87 mmol.kg(-1) d.m.), and no change (P > 0.05) in total muscle creatine. Biopsies
      pre- and post-creatine loading showed significant increases in total muscle
      creatine levels in both the left leg (Delta upward arrow 41.1 +/- 31.1 mmol.kg(
      1) d.m.) and the right leg (Delta upward arrow 36.6 +/- 19.8 mmol.kg(-1) d.m.),
      with no change in either leg's muscle glycogen content. After the final glycogen
      loading, a significant 53% increase in muscle glycogen (Delta upward arrow 241 +/
      150 mmol.kg-1 d.m.) was detected. Finally, the postcreatine load total glycogen
      content (694 +/- 156 mmol.kg(-1) d.m.) was significantly (P < 0.05) greater than
      the precreatine load total glycogen content (597 +/- 142 mmol.kg(-1) d.m.).
      CONCLUSION: It is suggested that a muscle's glycogen loading capacity is
      influenced by its initial levels of creatine and the accompanying alterations in
      cell volume.

PMID- 11445756
TI  - Physiological responses to short-term exercise in the heat after creatine
      loading.
AB  - PURPOSE: This investigation was designed to examine the influence of creatine
      (Cr) supplementation on acute cardiovascular, renal, temperature, and fluid
      regulatory hormonal responses to exercise for 35 min in the heat. METHODS: Twenty
      healthy men were matched and then randomly assigned to consume 0.3 g.kg(-1) Cr
      monohydrate (N = 10) or placebo (N = 10) for 7 d in a double-blind fashion.
      Before and after supplementation, both groups cycled for 30 min at 60-70%
      VO2(peak) immediately followed by three 10-s sprints in an environmental chamber
      at 37 degrees C and 80% relative humidity. RESULTS: Body mass was significantly
      increased (0.75 kg) in Cr subjects. Heart rate, blood pressure, and sweat rate
      responses to exercise were not significantly different between groups. There were
      no differences in rectal temperature responses in either group. Sodium,
      potassium, and creatinine excretion rates obtained from 24-h and exercise urine
      collection periods were not significantly altered in either group. Serum
      creatinine was elevated in the Cr group but within normal ranges. There were
      significant exercise-induced increases in cortisol, aldosterone, renin,
      angiotensin I and II, atrial peptide, and arginine vasopressin. The aldosterone
      response was slightly greater in the Cr (263%) compared with placebo (224%)
      group. Peak power was greater in the Cr group during all three 10-s sprints after
      supplementation and unchanged in the placebo group. There were no reports of
      adverse symptoms, including muscle cramping during supplementation or exercise.
      CONCLUSION: Cr supplementation augments repeated sprint cycle performance in the
      heat without altering thermoregulatory responses.

PMID- 11445757
TI  - Effect of altitude training on the peroxidation and antioxidant enzymes in
      sportsmen.
AB  - PURPOSE: The aim of this work was an evaluation of the influence of physical
      exercise in high-altitude conditions (about 2000 m above sea level) on
      thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD)
      and catalase (CAT) activities in 10 kayakers and 10 rowers. METHODS: During their
      training, the sportsmen performed different kinds of static and dynamic efforts.
      The blood samples were taken from the cubital vein on the control day at low
      altitude and at high altitude, and on the 4th, 10th, and 18th days of the
      training camp before and after exercise. The TBARS and lactic acid concentrations
      in blood plasma and SOD and CAT activities in erythrocytes were measured.
      RESULTS: A statistically significant increase of SOD and CAT activities in
      erythrocytes after exercise on the 4th, 10th, and 18th days of training was
      found. The TBARS concentration in erythrocytes decreased in a statistically
      significant way after the end of the 10th day of exercise (P < 0.01), and on 18th
      day it more than doubled (P < 0.001) when preexercise values were compared with
      postexercise values of each day. A statistically significant increase of TBARS
      concentration in blood plasma was observed only after the end of exercise on the
      10th day-using the same comparison as above. A statistically significant
      increased lactic acid concentration in blood plasma was noticed both on 4th or
      18th days of training. CONCLUSIONS: The results obtained show the increasing
      generation of oxygen-derived free radicals and the compensatory intensification
      of SOD and CAT activities after training in altitude (high mountain) conditions.

PMID- 11445758
TI  - Cardiac performance in endurance-trained and moderately active young women.
AB  - PURPOSE: To compare the cardiac performance of endurance-trained (ET) and
      moderately active (MA) young women before exercise and throughout incremental
      work rates to maximum with particular interest in whether their stroke volume
      (SV) levels off at a submaximal work rate or increases to maximum. METHODS: Blood
      volume (BV), and exercise cardiac performance were examined in seven ET (VO2max =
      64.3 +/- 2.0 mL.kg(-1).min(-1)) and seven MA (VO2max = 42.1 +/- 1.0 mL.kg(
      1).min(-1)) women, aged 18-30 yr. Cardiac time intervals were measured at matched
      heart rates (HR). RESULTS: ET had a significantly larger BV than MA in both mL
      (ET = 5053 +/- 139, MA = 4327 +/- 202) and mL.kg(-1) (ET = 83.1 +/- 1.4, MA =
      72.9 +/- 2.7). The SV of ET was significantly larger than the SV of MA throughout
      exercise, and the SV of ET increased progressively throughout incremental work
      rates to maximum. Although the SV of MA initially leveled off at a submaximal
      work rate, it underwent a secondary increase at very heavy work rates. Both
      diastolic filling rate (DFR) and left ventricular emptying rate (LVER) were
      significantly faster in ET compared with MA at HR of 150 bpm, 170 bpm and HRmax,
      and in both ET and MA, DFR was significantly faster than LVER at 170 bpm and
      HRmax. CONCLUSIONS: In young women, ET have a larger SV than MA due to an
      enhanced DFR and LVER, with the primary advantage being DFR (possibly due to
      their larger BV). In addition, the SV of ET increases progressively throughout
      incremental work rates to maximum with no plateau, whereas the SV of MA levels
      off through moderate to heavy work rates then undergoes a secondary increase at
      very heavy work rates.

PMID- 11445759
TI  - Intense endurance training on heart rate and blood pressure variability in
      runners.
AB  - Physical training with incomplete recovery times can produce significant fatigue.
      A study of cardiovascular responses showed that there is a sympathetic and a
      parasympathetic form of fatigue. PURPOSE: The purpose of this experimentation was
      to measure the effects of intense endurance training on autonomic balance through
      a spectral analysis study of the heart rate (HR) and systolic blood pressure
      (SBP). METHODS: Eight elite runners were tested twice: after a relative rest
      period (RRP) of 3 wk and after an 12-wk intense training period (ITP) for
      endurance. At the end of each phase, the subjects were tested by means of a
      VO2max test and a tilt-table test. RESULTS: The resting heart rate (HR)
      variability was lower (P < 0.001) in the intensive training phase. Likewise,
      there were differences in the low-frequency (0.04-0.150 Hz; LF) and high
      frequency (0.150-0.500 Hz; HF) components and the LF/HF ratio of the HR spectral
      analysis. The LF spectral power was significantly lower in the supine position (P
      < 0.05) during ITP. Upright tilting was accompanied by a 22.6% reduction in HF
      values during the rest period, whereas in ITP the HF spectral power rose by 31.2%
      (P < 0.01) during tilt, characterizing a greater parasympathetic system control.
      Sympathetic control represented by the LF/HF ratio regressed markedly (P < 0.01)
      in response to the tilt test in ITP. CONCLUSIONS: The spectral analysis of SBP in
      the high frequencies shows that the changes in cardiac parameters are coupled
      with a decrease in sympathetic vasomotor control (-18%) and a reduction in
      diastolic pressure (-3.2%) in the response to the tilt test at the end of ITP.
      Spectral analysis could be a means of demonstrating impairment of autonomic
      balance for the purpose of detecting a state of fatigue that could result in
      overtraining.

PMID- 11445760
TI  - CHAMPS physical activity questionnaire for older adults: outcomes for
      interventions.
AB  - PURPOSE: To evaluate effectively interventions to increase physical activity
      among older persons, reliable and valid measures of physical activity are
      required that can also detect the expected types of physical activity changes in
      this population. This paper describes a self-report physical activity
      questionnaire for older men and women, developed to evaluate the outcomes of the
      Community Healthy Activities Model Program for Seniors (CHAMPS), an intervention
      to increase physical activity. METHODS: The questionnaire assesses weekly
      frequency and duration of various physical activities typically undertaken by
      older adults. We estimated caloric expenditure/wk expended in physical activity
      and created a summary frequency/wk measure. We calculated measures of each of
      these for: 1) activities of at least moderate intensity (MET value >/= 3.0); and
      2) all specified physical activities, including those of light intensity. Six
      month stability was estimated on participants not likely to change (assessment
      only control group, physically active cohort). Several tests of construct
      validity were conducted, and sensitivity to change was analyzed based on response
      to the CHAMPS intervention. RESULTS: The sample (N = 249) comprised underactive
      persons (N = 173 from the CHAMPS trial) and active persons (N = 76). The sample
      was aged 65-90 yr (mean = 74, SD = 6); 64% were women, and 9% were minorities.
      Six-month stability ranged from 0.58 to 0.67, using intraclass correlation
      coefficients. Nearly all construct validity hypotheses were confirmed, though
      correlations were modest. All measures were sensitive to change (P < or = 0.01),
      with small to moderate effect sizes (0.38-0.64). CONCLUSIONS: The CHAMPS measure
      may be useful for evaluating the effectiveness of programs aimed at increasing
      levels of physical activity in older adults.

PMID- 11445761
TI  - Prevalence of physical activity during leisure time in the European Union.
AB  - PURPOSE: To estimate the prevalence of physical activity during leisure time in
      adults from the 15 member states of the European Union and the relationship with
      sociodemographic variables. METHODS: A representative sample, with approximately
      1000 adults, aged 15 and upward, was selected from each member state to complete
      a questionnaire on attitudes to physical activity, body weight, and health by a
      face-to-face interview, summing a total of 15,239 subjects. The amount of leisure
      time physical activity was quantified by assigning metabolic equivalents (METs)
      to each activity. Multiple linear regression models with MET-h.wk(-1) as the
      dependent variable were fitted. RESULTS: Northern European countries showed
      higher levels of physical activity than southern ones. The highest prevalence
      (91.9%) was found in Finland, and the lowest (40.7%) in Portugal. A higher
      percentage of men practiced any leisure-time physical activity and also showed
      higher mean of MET-h.wk(-1). In both genders, the multivariate models showed a
      significant trend to higher leisure time activity in participants with higher
      educational levels and in nonsmokers. Also, an inverse association between body
      mass index and leisure-time physical activity was found. CONCLUSION: The
      prevalence of any physical activity during leisure time in the adult European
      population was similar to the U.S. estimates. Nevertheless, the amount of
      activity is low, and a wide disparity between countries exists. To our knowledge,
      this is the first study determining the prevalence and amount of leisure-time
      physical activity, which is the first step to define strategies to persuade
      populations to increase their physical activity.

PMID- 11445762
TI  - Stage of readiness to exercise in ethnically diverse women: a U.S. survey.
AB  - PURPOSE: To assess stage of readiness to exercise and readiness to be physically
      active in a national survey of women aged 40 yr and over from various
      racial/ethnic groups (the U.S. Women's Determinants Study). METHOD: The
      prevalence of each stage was determined and compared across race/ethnicity. In
      addition, the level of misclassification between self-report of stage of
      readiness to exercise/be physically active and self-reported participation in
      specific exercise behavior was evaluated. RESULTS: Data were collected from a
      total of 2912 U.S. women via telephone survey over a 1-yr period (black 26%,
      American Indians/Alaskan Natives 25%, Hispanics 23%, and whites 26%). Over half
      the total sample was staged as currently undertaking regular exercise
      (maintenance stage, 55%), 25% indicated they were in precontemplation, and 15%
      were in contemplation stage. Few women were in preparation and action stages.
      There were statistically significant differences between the minority groups.
      Specifically, black women (OR 0.53, 95% 0.31-0.91) were less likely to be in the
      active stages (e.g., preparation, action, maintenance) than Hispanics and Alaskan
      Native/American Native women, and this was true after controlling for important
      sociodemographic and health variables (age, education, BMI, and smoking). The
      additional analysis of a modified stage question developed to assess readiness to
      be more physically active (150 min.wk(-1)) may have provided inflated results
      (82% in maintenance), possibly due to the complexity of the questions. The level
      of misclassification between measures ranged from 5 to 20%. CONCLUSION: These
      results have important implications for the use of stage of change measures with
      populations of older ethnically diverse women particularly and the popularity of
      modifying stage questions to reflect "lifestyle" or moderate-intensity physical
      activity.

PMID- 11445763
TI  - Multi-segment coordination: fatigue effects.
AB  - PURPOSE: The aim of this study was to investigate the segmental coordination of
      vertical jumps under fatigue. METHODS: Twelve subjects performed maximal
      countermovement jumps with and without fatigue, which was imposed by maximal
      continuous jumps in place until their maximal jump height corresponded to 70% of
      the nonfatigued condition. Video, ground reaction forces, and electromyographic
      signals were recorded to analyze the segmental coordination of countermovement
      jumps before (CMJ1) and after (CMJ2) fatigue. The magnitude of joint extension
      initiation, peak joint angular velocity, and peak net power around the ankle,
      knee, and hip joints and their respective times were determined. RESULTS: CMJ2
      was characterized by a longer contact time, which was accompanied with an earlier
      movement initiation and several differences (P < 0.05) in the variables used to
      describe coordination. When the movement duration was normalized with respect to
      the contact phase duration, the differences between CMJ1 and CMJ2 were not
      sustained. A consistent pattern was indicated, in which the segmental
      coordination did not differ between jump conditions. When the magnitude of the
      muscle activation was set aside, a remarkably consistent muscle activation time
      was noticed between conditions. CONCLUSIONS: It was indicated that
      countermovement jumps were performed with a consistent well-timed motion of the
      segments. A "common drive," which acts without the knowledge of the muscle
      properties, was suggested as mediating and controlling the muscle activation
      timing between agonist-antagonist muscle pairs.

PMID- 11445764
TI  - External loading of the knee joint during running and cutting maneuvers.
AB  - PURPOSE: To investigate the external loads applied to the knee joint during
      dynamic cutting tasks and assess the potential for ligament loading. METHODS: A
      50-Hz VICON motion analysis system was used to determine the lower limb
      kinematics of 11 healthy male subjects during running, sidestepping, and
      crossover cut. A kinematic model was used in conjunction with force place data to
      calculate the three-dimensional loads at the knee joint during stance phase.
      RESULTS: External flexion/extension loads at the knee joint were similar across
      tasks; however, the varus/valgus and internal/external rotation moments applied
      to the knee during sidestepping and crossover cutting were considerably larger
      than those measured during normal running (P < 0.05). Sidestepping tasks elicited
      combined loads of flexion, valgus, and internal rotation, whereas crossover
      cutting tasks elicited combined loads of flexion, varus, and external rotation.
      CONCLUSION: Compared with running, the potential for increased ligament loading
      during sidestepping and crossover cutting maneuvers is a result of the large
      increase in varus/valgus and internal/external rotation moments rather than any
      change in the external flexion moment. The combined external moments applied to
      the knee joint during stance phase of the cutting tasks are believed to place the
      ACL and collateral ligaments at risk of injury, particularly at knee flexion
      angles between 0 degrees and 40 degrees, if appropriate muscle activation
      strategies are not used to counter these moments.

PMID- 11445765
TI  - Anticipatory effects on knee joint loading during running and cutting maneuvers.
AB  - PURPOSE: To determine how unanticipated performance of cutting maneuvers in sport
      affects the external loads applied to the knee joint and the potential risk for
      ligament injury. METHODS: A 50-Hz VICON motion analysis system was used to
      determine the lower limb kinematics of 11 healthy male subjects during running
      and cutting tasks performed under preplanned (PP) and unanticipated (UN)
      conditions. Subjects performed the UN tasks in response to a light stimulus on a
      target board. A kinematic model was then used in conjunction with force place
      data to calculate the three-dimensional loads at the knee joint. RESULTS:
      External flexion/extension moments at the knee joint were similar between PP and
      UN conditions; however, the varus/valgus and internal/external rotation moments
      during the UN cutting tasks were up to twice the magnitude of the moments
      measured during the PP condition. CONCLUSION: Cutting maneuvers performed without
      adequate planning may increase the risk of noncontact knee ligament injury due to
      the increased external varus/valgus and internal/external rotation moments
      applied to the knee. These results are probably due to the small amount of time
      to make appropriate postural adjustments before performance of the task, such as
      the position of the foot on the ground relative to the body center of mass.
      Subsequently, training for the game situation should involve drills that
      familiarize players with making unanticipated changes of direction. Practice
      sessions should also incorporate plyometrics and should focus on better
      interpretation of visual cues to increase the time available to preplan a
      movement.

PMID- 11445766
TI  - Strategies for maintaining a handstand in the anterior-posterior direction.
AB  - PURPOSE: The purpose of this analysis was to determine the contributions made by
      wrist, shoulder, and hip joint torques in maintaining a handstand. METHODS:
      Handstand balances (N = 6) executed on a force plate and recorded with two
      genlocked video cameras were subjected to inverse dynamics analysis to determine
      anterior-posterior joint torques at the wrists, shoulders, and hips. Multiple
      regression analyses were conducted to investigate which of the joint torques were
      influential in accounting for anterior-posterior whole-body mass center (CM)
      movement. RESULTS: Results demonstrated that, in general, all calculated joint
      torques contributed to CM movement. In a number of trials, wrist torque played a
      dominant role in accounting for CM variance. Ostensibly, superior handstand
      balances are characterized by important contributions from wrist torques and
      shoulder torques with little influence from hip torques. In contrast, hip torques
      were found to be increasingly influential in less successful balances.
      CONCLUSIONS: It is concluded that multiple joints are utilized in maintaining a
      handstand balance in the anterior-posterior direction, and there appears to be
      two joint involvement strategies, which supports similar findings from postural
      research on normal upright stance.

PMID- 11445767
TI  - Specific respiratory warm-up improves rowing performance and exertional dyspnea.
AB  - PURPOSE: The purpose of this study was a) to compare the effect of three
      different warm-up protocols upon rowing performance and perception of dyspnea,
      and b) to identify the functional significance of a respiratory warm-up. METHODS:
      A group of well-trained club rowers (N = 14) performed a 6-min all-out rowing
      simulation (Concept II). We examined differences in mean power output and dyspnea
      measures (modified CR-Borg scale) under three different conditions: after a
      submaximal rowing warm-up (SWU), a specific rowing warm-up (RWU), and a specific
      rowing warm-up with the addition of a respiratory warm-up (RWUplus) protocol.
      RESULTS: Mean power output during the 6-min all-out rowing effort increased by
      1.2% after the RWUplus compared with that obtained after the RWU (P < 0.05)
      which, in turn, was by 3.2% higher than the performance after the SWU (P < 0.01).
      Similarly, after the RWUplus, dyspnea was 0.6 +/- 0.1 (P < 0.05) units of the
      Borg scale lower compared with the dyspnea after the RWU and 0.8 +/- 0.2 (P <
      0.05) units lower than the dyspnea after the SWU. CONCLUSION: These data suggest
      that a combination of a respiratory warm-up protocol together with a specific
      rowing warm-up is more effective than a specific rowing warm-up or a submaximal
      warm-up alone as a preparation for rowing performance.

PMID- 11445768
TI  - Muscle strength in knee varus and valgus.
AB  - PURPOSE: The purpose of this study was to investigate the lower-limb muscle
      strength in knee varus-valgus and its dependence on knee varus-valgus position.
      The hypothesis was that humans could differentially contract the medial and
      lateral muscles crossing the knee and generate significant moments in knee valgus
      varus. METHODS: The subjects sat with the knee at full extension and secured from
      the medial, lateral, anterior, and posterior sides. Both hips were clamped from
      the lateral sides. The subjects adducted (abducted) the ipsilateral hip during
      the knee valgus (varus) maximal voluntary contraction with EMG signals recorded
      from muscles crossing the knee and knee joint moments measured using a six-axis
      force sensor. Frontal plane tibiofemoral movement was evaluated using a
      fluoroscope. RESULTS AND CONCLUSIONS: The subjects differentially contracted the
      medial and lateral muscles, and fluoroscope images showed the corresponding
      tibiofemoral movement. The subjects showed considerable strength in knee varus
      and valgus. The active knee varus strength increased significantly with
      increasing knee valgus angle, and the valgus strength was significantly higher
      when the knee was in varus position (P < 0.039). Active valgus muscle strength at
      5 degrees knee varus was significantly higher than the active varus strength at 5
      degrees valgus (P = 0.002). The passive resistance moment increased linearly with
      increasing knee valgus and varus angles, and it accounted for 28% and 35% of the
      total (active plus passive) moment at the 5 degrees varus and 5 degrees valgus,
      respectively. The significant varus-valgus muscle strength demonstrated in this
      study may play important roles in performing various functional tasks,
      maintaining joint stability, and preventing potential injuries, whether the major
      load and motion at the knee is in the frontal plane or not.

PMID- 11445769
TI  - Acute muscle damage as a stimulus for training-induced gains in strength.
AB  - PURPOSE: The purpose of this study was to investigate the effect of a single
      acute bout of maximal eccentric work upon the strength gains during 9 subsequent
      weeks of strength training. Eccentric work causes acute muscle damage that may
      initiate compensatory hypertrophy and enhance training-induced gains in strength.
      METHODS: Twenty-six healthy adults (21 +/- 1 yr, 7 women) trained the elbow
      flexors 3 d per week for 9 wk. One arm (C) performed purely conventional isotonic
      training, i.e., lifting and lowering. The other arm (E) began with a single bout
      of maximal eccentric work but thereafter undertook identical isotonic training.
      Every week dynamic lifting strength (1 RM) and isometric strength were measured.
      RESULTS: The results indicated that an acute bout of eccentric muscle damage does
      not accentuate training-induced gains in strength. Isometric strength of arm E
      fell by 15 +/- 2% (mean +/- SEM) 2 d after the bout of eccentric work, and, 4 d
      afterward, plasma creatine kinase levels were 1502 +/- 397 IU.L-1. Although arm E
      displayed rapid gains in strength from 2 d after the bout of eccentric work,
      these were not sustained, and for several weeks arm E showed significantly
      smaller gains in strength than arm C (isometric strength, 2 wk; dynamic lifting
      strength, 5 wk). CONCLUSIONS: After 9 wk of training, the gains in both isometric
      and dynamic lifting strength were similar for the two arms. A single bout of
      damaging eccentric work did not enhance the response to conventional strength
      training and significantly compromised strength gains for several weeks.

PMID- 11445770
TI  - Effects of standard and eccentric overload strength training in young women.
AB  - PURPOSE: According to the force-velocity relationship of human skeletal muscle,
      the maximal load one can lift is limited by the concentric movement phase, and
      the eccentric phase is always underloaded. In the present study, we hypothesized
      that acute exercise training using an eccentric overload compared with standard
      loading would lead to greater neuromuscular and strength adaptations. METHODS:
      Sedentary women (age 20.9 yr) were tested for concentric and eccentric three
      repetition maximum (3RM), maximal isokinetic eccentric and concentric and
      isometric force and associated EMG activity of selected thigh muscles before and
      after 7 consecutive days of exercise training of the left quadriceps. The
      exercise program was designed so that the total weight lifted was similar between
      the eccentric overload (EO, N = 10) and standard group (ST, N = 10), but EO
      exercised with about 50% greater eccentric load whereas the controls did not
      exercise (N = 10). RESULTS: There was a 22% increase in the total weight lifted
      over 7 d. On the average, EOs compared with STs strength gains were approximately
      twofold greater. Changes in EMG paralleled the changes in muscle strength without
      changes in biceps femoris coactivity during knee extension. CONCLUSION: Because
      the strength gains were achieved by exercising at low intensities and over a
      short time period, exercise prescription of eccentric overloading appears
      especially suitable for elders, individuals deconditioned due to an injury, and
      the chronically diseased.

PMID- 11445771
TI  - Acute adaptation to low volume eccentric exercise.
AB  - PURPOSE: Many symptoms of eccentric muscle damage can be substantially reduced if
      a similar eccentric bout is repeated within several weeks of the initial bout.
      The purpose of this study was to determine whether a nondamaging, low repetition,
      low volume eccentric exercise bout could also provide a protective/adaptive
      effect. METHODS: Subjects were assigned to a control (CON), eccentric exercise
      (ECC), or low volume familiarized eccentric exercise group (LV+ECC). Before the
      study, the LV+ECC group performed six maximal eccentric contractions during two
      familiarization sessions. The main eccentric bout targeted the elbow flexor
      muscle group and consisted of 36 maximal eccentric contractions. Muscle soreness,
      upper arm girth, elbow angle, creatine kinase activity, isometric torque, and
      concentric and eccentric torque at 0.52 and 3.14 rad.s-1 were assessed 0, 1, 2,
      3, 4, 7, and 10 d postexercise. RESULTS: No evidence of muscle damage was
      observed as a result of the low volume eccentric bouts. Nevertheless, with the
      exception of muscle soreness and concentric torque, all variables recovered more
      rapidly in the LV+ECC group (P < 0.05). CONCLUSION: Adaptation to eccentric
      exercise can occur in the absence of significant muscle damage. Exposure to a
      small number of nondamaging eccentric contractions can significantly improve
      recovery after a subsequent damaging eccentric bout. Furthermore, this adaptation
      appears to be mode-specific and not applicable to concentric contractions.

PMID- 11445772
TI  - Progressive versus rapid rate of contraction during 7 wk of isometric resistance
      training.
AB  - PURPOSE: The aim of this study was to compare the effects of isometric training
      performed with progressive versus rapid rate of contraction on the knee extensor
      neuromuscular properties over a 7-wk period. METHODS: Sixteen healthy male
      subjects trained quadriceps femoris muscle in a leg extension machine three times
      a week during 7 wk. The training sessions consisted of six sets of six maximal
      isometric contractions. A first group trained by performing progressive
      contractions lasting 4 s, whereas a second group performed contractions with a
      rapid rate of contraction (i.e., ballistic contractions) lasting about 1 s.
      RESULTS: Both groups significantly increased the isometric and isokinetic
      voluntary torque, and the respective absolute or relative gains were comparable.
      Isometric training performed with progressive rate of contraction affected the
      evoked action potential (M wave) of the vastus lateralis muscle and not the
      related twitch properties. On the other hand, the isometric training completed
      with ballistic contractions significantly modified the twitch contractile
      properties of the knee extensors and not the associated M waves of both vastus
      medialis and vastus lateralis. CONCLUSION: Knee extensors adapted specifically
      their neuromuscular properties to the type of rate of contraction performed
      during 7-wk isometric resistance training. Progressive isometric contractions
      produced modifications of the nervous system at peripheral level (i.e., muscle
      membrane electrical activity), whereas ballistic isometric contractions affected
      the knee extensor contractile muscle properties (i.e., excitation-contraction
      coupling).

PMID- 11445773
TI  - Competition performance and basal nocturnal catecholamine excretion in cross
      country skiers.
AB  - Objective techniques to determine whether an athlete is optimally prepared for a
      competition are virtually nonexistent. Preparedness for sports competition is
      commonly judged through the experience of the athletes and their coaches.
      Evidence from overtraining studies suggests that catecholamine (Cat) excretion
      rates may correlate with performance in athletes. PURPOSE: We therefore attempted
      to determine whether a relationship existed between performances of world-class
      cross-country skiers and basal nocturnal Cat excretion (BNCE). METHOD: During the
      Cross-Country Skiing World Championships, we determined BNCE in nine cross
      country skiers of the Swiss national team by measuring free Cat concentration
      (dopamine = D, norepinephrine = NE, epinephrine = E) in morning urine samples,
      using high performance liquid chromatography. Expert judgments of competition
      performance (ECP) were assessed by two experienced professional coaches of the
      national team by using an 11-step scale. RESULTS: The BNCE correlated
      significantly with ECP in cross-country skiers (r2 = 0.84 and P < for NE; r2 =
      0.86 and P < 0.001 for D). Athletes who had their best absolute competition
      results (ACR) showed the highest NE and D concentrations. CONCLUSION: These data
      suggest that competitive cross-country skiers with higher D and NE excretion may
      reach better competition levels compared with those with lower levels. Measures
      of BNCE provide objective information about competition performance, which may
      benefit athletes in their precompetition preparation.

PMID- 11445774
TI  - Evaluation of methods to assess physical activity in free-living conditions.
AB  - PURPOSE: The purpose of this study was to compare different methods of measuring
      physical activity (PA) in women by the doubly labeled water method (DLW).
      METHODS: Thirteen subjects participated in a 7-d protocol during which total
      daily energy expenditure (TDEE) was measured with DLW. Body composition, basal
      metabolic rate (BMR), and peak oxygen consumption were also measured. Physical
      activity-related energy expenditure (PAEE) was then calculated by subtracting
      measured BMR and the estimated thermic effect of food from TDEE. Simultaneously,
      over the 7 d, PA was assessed via a 7-d Physical Activity Recall questionnaire
      (PAR), and subjects wore secured at the waist, a Tritrac-R3D (Madison, WI), a
      Computer Science Application Inc. activity monitor (CSA; Shalimar, FL), and a
      Yamax Digi Walker-500 (Tokyo, Japan). Pearson-product moment correlations were
      calculated to determine the relationships among the different methods for
      estimating PAEE. Paired t-tests with appropriate adjustments were used to compare
      the different methods with DLW-PAEE. RESULTS: There was no significant difference
      between PAEE determined from PAR and DLW. The differences between the two methods
      ranged from -633 to 280 kcal.d(-1). Compared with DLW, PAEE determined from CSA,
      Tritrac, and Yamax was significantly underestimated by 59% (-495 kcal.d(-1)), 35%
      (-320 kcal.d(-1)) and 59% (-497 kcal.d(-1)), respectively. VO2peak explained 43%
      of the variation in DLW-PAEE. CONCLUSION: Although the group average for PAR-PAEE
      agreed with DLW-PAEE, there were differences in the methods among the subjects.
      PAEE determined by Tritrac, CSA, and Yamax significantly underestimate free
      living PAEE in women.

PMID- 11445775
TI  - Leg electromyography and the VO2-power relationship during bicycle ergometry.
AB  - PURPOSE: The relationship between oxygen consumption and power is not linear. The
      purpose of this investigation was to examine the nature of the relationship and
      the cause of the nonlinearity. METHODS: Eight male cyclists (60.5 +/- 3.8 mL
      O2.min-1.kg(-1) VO2 peak) completed an incremental exercise test (1 W.5 s(-1)) to
      exhaustion. VO2 was measured every breath, and rmsEMG was recorded continuously
      over the belly of vastus lateralis, biceps femoris, and lateral gastrocnemius.
      RESULTS: VO2 is a linear function of power in moderate exercise; the slope of the
      linear portion was approximately 9.7 mL O2.min(-1).W(-1), which is consistent
      with the steady state gain for moderate exercise. Beyond this initial break from
      linearity, the VO2.W(-1) plot demonstrates a second break that is not different
      from the point of respiratory compensation (break in VE.VCO2(-1)). These breaks
      were coincident with increased neuromuscular activity (1st break: 194 +/- 27 W
      for VO2, 191 +/- 25 W for vastus lateralis; 2nd break: 262 +/- 34 W for VO2, 258
      +/- 27 W for vastus lateralis) and corresponded to approximately 58% VO2 peak for
      the first and 75% VO2 peak for the second break. CONCLUSIONS: VO2 is not a linear
      function of power. During an incremental test, neuromuscular activity and VO2
      increase more rapidly in heavy exercise. Both VO2 and neuromuscular activity
      exhibit a second break at very high power output, which may mark an upper limit
      for sustainable exercise.

PMID- 11445776
TI  - What is going on with levothyroxine.

PMID- 11445777
TI  - Caspofungin (Cancidas) for aspergillosis.

PMID- 11445778
TI  - Initial treatment of Parkinson's disease: wait just a minute.

PMID- 11445781
TI  - Managing acute pediatric asthma: keeping it short.

PMID- 11445782
TI  - Evolving concepts and improving prospects for neonates with short bowel syndrome.

PMID- 11445783
TI  - The use of short-acting nifedipine in children with hypertension: another example
      of the need for comprehensive drug testing in children.

PMID- 11445784
TI  - Effects of metabolic disorders on the brain: can these effects be reversed with
      bone marrow transplantation?

PMID- 11445785
TI  - Behavioral challenges and functional imaging: where the rubber meets the road.

PMID- 11445786
TI  - The impact of pediatric obesity treatment on eating behavior and psychologic
      adjustment.

PMID- 11445787
TI  - "Conscious sedation": time for this oxymoron to go away!

PMID- 11445789
TI  - Comparative efficacy of oral dexamethasone versus oral prednisone in acute
      pediatric asthma.
AB  - OBJECTIVE: The objective was to determine whether 2 days of oral dexamethasone
      (DEX) is more effective than 5 days of oral prednisone/prednisolone (PRED) in
      improving symptoms and preventing relapse in children with acute asthma. STUDY
      DESIGN: This was a prospective randomized trial of children (2 to 18 years old)
      who presented to the emergency department with acute asthma. PRED 2 mg/kg,
      maximum 60 mg (odd days) or DEX 0.6 mg/kg, maximum 16 mg (even days) was used. At
      discharge children in the PRED group were prescribed 4 daily doses (1 mg/kg/d,
      maximum 60 mg); children in the DEX group received a prepackaged dose (0.6 mg/kg,
      maximum 16 mg) to take the next day. The primary outcome was relapse within 10
      days. RESULTS: When DEX was compared with PRED, relapse rates (7.4% of 272 vs
      6.9% of 261), hospitalization rates from the emergency department (11% vs 12%) or
      after relapse (20% vs 17%), and symptom persistence at 10 days (22% vs 21%) were
      similar. In the PRED group more children were excluded for vomiting in the
      emergency department (3% vs 0.3%; P =.008), more parents were noncompliant (4%
      vs. 0.4%; P =.004), and more children missed > or =2 days of school (19.5% vs.
      13.2%; P =.05). CONCLUSION: In children with acute asthma, 2 doses of
      dexamethasone provide similar efficacy with improved compliance and fewer side
      effects than 5 doses of prednisone.

PMID- 11445790
TI  - Nutritional and other postoperative management of neonates with short bowel
      syndrome correlates with clinical outcomes.
AB  - OBJECTIVE: To determine correlates of clinical outcomes in patients with short
      bowel syndrome (SBS). METHODS: Retrospective medical record review of neonates
      treated between 1986 and 1998 who met our criteria for SBS: dependence on
      parenteral nutrition (PN) for at least 90 days after surgical therapy for
      congenital or acquired intestinal diseases. RESULTS: Thirty subjects with
      complete data were identified; 13 (43%) had necrotizing enterocolitis, and 17
      (57%)had intestinal malformations. Mean (SD) residual small bowel length was 83
      (67) cm. Enteral feeding with breastmilk (r = -0.821) or an amino acid-based
      formula (r = -0.793) was associated with a shorter duration of PN, as were longer
      residual small bowel length (r = -0.475) and percentage of calories received
      enterally at 6 weeks after surgery(r = -0.527). Shorter time without diverting
      ileostomy or colostomy (r = 0.400), enteral feeding with a protein hydrolysate
      formula (r = -0.476), and percentage of calories received enterally at 6 weeks
      after surgery (r = -0.504) were associated with a lower peak direct bilirubin
      concentration. Presence of an intact ileocecal valve and frequency of catheter
      related infections were not significantly correlated with duration of PN. In
      multivariate analysis, only residual small bowel length was a significant
      independent predictor of duration of PN, and only less time with a diverting
      ostomy was an independent predictor of peak direct bilirubin concentration.
      CONCLUSIONS: Although residual small bowel length remains an important predictor
      of duration of PN use in infants with SBS, other factors, such as use of breast
      milk or amino acid-based formula, may also play a role in intestinal adaptation.
      In addition, prompt restoration of intestinal continuity is associated with
      lowered risk of cholestatic liver disease. Early enteral feeding after surgery is
      associated both with reduced duration of PN and less cholestasis.

PMID- 11445791
TI  - The use of short-acting nifedipine in pediatric patients with hypertension.
AB  - OBJECTIVE: To evaluate the use of short-acting nifedipine for treatment of severe
      hypertension in children. STUDY DESIGN: A retrospective chart review of 520
      nifedipine doses given for severe hypertension in 117 pediatric patients was
      completed. Nifedipine dose, systolic and diastolic blood pressures before and
      within 2 hours of the dose, and side effects were recorded. Pre- and post-dose
      mean arterial pressure (MAP) and percent reductions in MAP and systolic and
      diastolic blood pressure were calculated. Age, dose, primary diagnosis, and use
      of other antihypertensive agents were examined with respect to blood pressure
      reduction. RESULTS: Of the doses received, 35% were associated with > or =25%
      reduction in MAP, a degree of MAP reduction previously associated with
      hypertension treatment complications. MAP percent reduction was correlated with
      nifedipine dose adjusted for weight (r = 0.24, P<.001). Mean nifedipine doses per
      kilogram were larger in patients who had > or =25% MAP reduction compared with
      those who had <25% MAP reduction (0.26 +/- 0.12 mg/kg vs. 0.21 +/- 0.11 mg/kg, F
      = 29.01, P <.001). Adolescents received lower nifedipine doses per kilogram and
      had lower percent reduction in blood pressure compared with younger children. No
      clinically significant side effects were noted after administration of
      nifedipine. CONCLUSION: Precipitous reductions in blood pressure are ameliorated
      by decreasing the initial nifedipine dose to < or =0.25 mg/kg in pediatric
      patients. Short-acting nifedipine use in pediatric patients with hypertension in
      a hospital setting is safe.

PMID- 11445792
TI  - Intravenous nicardipine for treatment of severe hypertension in children.
AB  - OBJECTIVE: To examine the effect of intravenous nicardipine in the treatment of
      children with severe hypertension. METHODS: The medical records of 29 children
      (mean age 94 months) treated with intravenous nicardipine were retrospectively
      reviewed. The mean duration of severe hypertension before nicardipine use was
      12.5 hours. Most (74%) patients were receiving other antihypertensive agents
      before nicardipine. RESULTS: The initial nicardipine dose was 0.8 +/- 0.3
      microg/kg/min (mean +/- SD). The mean effective dose was 1.8 +/- 1.0
      microg/kg/min (range, 0.3 to 4.0). Blood pressure control was achieved within 2.7
      +/- 2.1 hours after nicardipine was started. Nicardipine treatment produced a 16%
      reduction in systolic blood pressure, a 23% reduction in diastolic blood
      pressure, and a 7% increase in heart rate. Nicardipine was effective as a single
      agent on 26 (84%) of 31 occasions. Adverse effects included tachycardia,
      flushing, palpitations, and hypotension. CONCLUSIONS: When administered in the
      intensive care unit setting with close patient monitoring, intravenous
      nicardipine effectively lowered blood pressure in children with severe
      hypertension. Larger prospective studies should be conducted to confirm these
      findings.

PMID- 11445793
TI  - Cognitive and behavioral abnormalities in adenosine deaminase deficient severe
      combined immunodeficiency.
AB  - OBJECTIVE: The objective was to evaluate the cognitive, behavioral, and
      neurodevelopmental function in patients with adenosine deaminase deficient severe
      combined immunodeficiency (ADA-SCID) and to compare the findings with those of a
      case control group of patients without ADA-SCID. STUDY DESIGN: Case-matched pairs
      of patients with ADA-SCID (n = 11) and patients without ADA-SCID who had
      undergone bone marrow transplantation were recruited. Subjects were assessed by
      age-appropriate standard tests of intelligence, behavior, and neurodevelopment.
      RESULTS: Cognitive ability was not significantly different between the 2 groups,
      but patients with ADA-SCID showed a significant inverse correlation between
      deoxyadenosinetrisphosphate levels at diagnosis and IQ (P =.048). Behavioral
      assessment showed that patients with ADA-SCID functioned in the pathologic range
      on all domains, whereas mean scores for the control group were within normal
      limits. Behavioral impairment in patients with ADA-SCID also showed a significant
      positive correlation with age (P =.026). CONCLUSIONS: Cognitive function in ADA
      deficiency is adversely affected by the severity of metabolic derangement at the
      time of diagnosis. In addition, patients with ADA-SCID have significant
      behavioral abnormalities after transplantation. These defects are not due to the
      transplant procedure but reflect the systemic nature of ADA deficiency. These
      findings have important implications for future medical and nonmedical management
      strategies.

PMID- 11445794
TI  - Neural substrates of anorexia nervosa: a behavioral challenge study with positron
      emission tomography.
AB  - OBJECTIVE: To delineate functional brain abnormalities associated with anorexia
      nervosa (AN). STUDY DESIGN: Positron emission tomographic measurements of
      regional cerebral blood flow (rCBF) were performed on 8 female patients with AN
      and 8 healthy female control subjects during exposure to 3 types of stimuli: high
      calorie foods, low-calorie foods, and non-food items. Heart rate and internal
      state analog scale scores were also obtained. Stereotactic transformation and
      statistical parametric mapping techniques were used to analyze imaging data.
      RESULTS: During the high-calorie condition, control subjects reported a
      significant desire to eat, whereas subjects with AN reported elevated anxiety and
      exhibited increases in heart rate. Patients with AN had elevated bilateral medial
      temporal lobe rCBF compared with control subjects. Planned comparisons for group
      by-condition interactions demonstrated greater activation within left occipital
      cortex and right temporo-occipital cortex for the high-calorie versus low-calorie
      contrast in patients with AN compared with control subjects. CONCLUSIONS: Our
      finding of elevated rCBF within bilateral medial temporal lobes is similar to
      published results in patients with psychotic disorders and may be related to the
      body image distortion common to AN. The high-calorie food phobia exhibited by
      patients with AN appears to be associated with exaggerated responses in visual
      association cortex, as has been previously observed in studies of specific
      phobias.

PMID- 11445795
TI  - Changes in eating disorder symptoms with pediatric obesity treatment.
AB  - OBJECTIVE: To evaluate the effects of behavioral, family-based treatment on
      disordered eating and child behavior problems for obese 8- to 12-year-old
      children. STUDY DESIGN: We examined disordered eating in children and parents
      using the Kids' Eating Disorder Survey (KEDS) and the Binge Eating Scale,
      respectively; and psychologic problems in children and their parents using the
      Child Behavior Checklist and Symptom Checklist-90, respectively, in 47 families
      who participated in a family-based obesity treatment program. RESULTS: Obese
      children showed significant decreases (-12.5 +/- 13.5) in percent overweight,
      internalizing problems (-7.0 +/- 7.3), and total behavior problems (-4.8 +/- 6.6)
      and increases in behavioral competence (3.7 +/- 5.0) over 2 years of measurement;
      and their parents showed significant decreases in weight (-5.0 +/- 8.3 kg) and
      reductions in parental distress (-2.3 +/- 7.6) and in disturbed eating and weight
      related cognition (-3.2 +/- 5.3). No significant changes were observed in total
      KEDS (-0.2 +/- 1.9), weight dissatisfaction (-0.3 +/- 1.7), or
      purging/restricting (0.2 +/- 0.6) scores. Decreases in total KEDS were related to
      decreases in total behavior problems and externalizing behavior problems.
      CONCLUSIONS: These results document improvements in child behavior problems and
      competence and no change in symptoms of disordered eating in a standardized
      behavioral weight control program.

PMID- 11445796
TI  - Predictors of cost of liver transplantation in children: a single center study.
AB  - OBJECTIVE: Efforts to decrease the cost of orthotopic liver transplantation (OLT)
      must address the impact of specific interventions on clinical outcome. We
      hypothesized that an intervention designed to decrease the length of
      hospitalization would reduce costs without jeopardizing clinical outcome. We
      further sought to identify predictors of length of stay and cost for
      hospitalization after liver transplantation. METHODS: The study group included 47
      children who underwent OLT from September 1996 to April 1999, and the control
      group included 36 children who underwent OLT from March 1994 to August 1996. The
      intervention was a transition to home program in which patients were discharged
      to a family living center when they met established clinical criteria and their
      families met predefined educational goals. We analyzed patients who survived 3
      months after OLT. RESULTS: For the intervention group, the mean length of stay,
      total costs, and surgical costs were 29%, 36%, and 34% lower, respectively. Organ
      type, height z score, race, hepatic artery thrombosis, early allograft rejection,
      and participation in the transition to home program predicted length of stay and
      total costs. CONCLUSION: An early discharge program based on defined criteria can
      be used to decrease length of stay and cost after OLT without jeopardizing
      clinical outcome.

PMID- 11445797
TI  - Nonadherence is associated with late rejection in pediatric heart transplant
      recipients.
AB  - OBJECTIVES: The objective was to study the impact of nonadherence on late
      rejection after pediatric heart transplantation. STUDY DESIGN: This was a
      retrospective cohort study of cardiac transplant recipients surviving >6 months
      (n = 50). Patients were stratified by episodes of late rejection. End points were
      defined by cyclosporin A (CSA) level, CSA level variability, and patient
      admission of nonadherence. RESULTS: In 15 patients there were 49 episodes of late
      rejection, and 37 (76%) were associated with nonadherence. Of these patients, 7
      of 15 died, and 3 of 15 had transplant coronary artery disease. Risk factors for
      the rejection were single-parent home, non-white, older age, and higher CSA level
      variability. In 35 nonrejectors there were 4 deaths from sepsis, post-transplant
      lymphoproliferative disease, renal failure, and encephalomyelitis. CONCLUSION:
      Late rejection after pediatric heart transplantation is associated with
      nonadherence, is common during adolescence, and is associated with poor outcome.

PMID- 11445798
TI  - Long-term clinical outcome in patients with glutathione synthetase deficiency.
AB  - OBJECTIVE: The objective was to determine the long-term clinical outcome and the
      effects of treatment of patients with glutathione synthetase (GS) deficiency (n =
      28). METHODS: The diagnosis was based on demonstration of a marked decrease in GS
      activity in erythrocytes or cultured fibroblasts in all patients and was
      supported by finding a decrease in erythrocyte or fibroblast glutathione,
      presence of 5-oxoprolinuria, or both. The treatment varied but usually included
      correction of acidosis and supplementation with vitamins C and/or E. RESULTS:
      Sixteen patients were severely affected with neurologic symptoms such as seizures
      and psychomotor retardation; 7 had died at the time of the study. None of the
      severely affected patients had been treated with both vitamins C and E from the
      neonatal period. No significant difference was found in GS activity between
      patients with or without neurologic symptoms or in erythrocyte or fibroblast
      glutathione levels. Five patients had recurrent bacterial infections. CONCLUSION:
      On the basis of clinical symptoms, patients with GS deficiency can be classified
      into 3 phenotypes: mild, moderate, and severe. Our results indicate that early
      supplementation with vitamins C and E may improve the long-term clinical outcome.

PMID- 11445799
TI  - Surfactant protein deficiency in familial interstitial lung disease.
AB  - OBJECTIVE: To determine the contribution of surfactant protein abnormalities to
      the development of chronic lung injury in a familial form of interstitial lung
      disease. STUDY DESIGN: An 11-year-old girl, her sister, and their mother who were
      diagnosed with chronic interstitial lung disease underwent laboratory
      investigation of surfactant protein expression in bronchoalveolar lavage fluid
      and lung biopsy specimens. Nineteen patients with idiopathic pulmonary fibrosis
      and 9 patients who were investigated for pulmonary malignancy but who did not
      have interstitial lung disease served as control subjects. RESULTS: The 3 family
      members were found to have absent surfactant protein C (SP-C) and decreased
      levels of SP-A and SP-B in bronchoalveolar lavage fluid (BALF). Immunostaining
      for pulmonary surfactant proteins in lung biopsy specimens obtained from both
      children demonstrated a marked decrease of pro-SP-C in the alveolar epithelial
      cells but strong staining for pro-SP-B, SP-B, SP-A, and SP-D. No deviations from
      published surfactant protein B or C coding sequences were identified by DNA
      sequence analysis. All control subjects had a detectable level of SP-C in the
      BALF. CONCLUSION: The apparent absence of SP-C and a decrease in the levels of SP
      A and SP-B are associated with familial interstitial lung disease.

PMID- 11445800
TI  - Short-course versus conventional length antimicrobial therapy for uncomplicated
      lower urinary tract infections in children: a meta-analysis of 1279 patients.
AB  - OBJECTIVE: The objective was to compare the efficacies of single-dose, short
      course (4 days or less), and standard course (5 days or greater) antimicrobial
      therapy for uncomplicated childhood cystitis. METHODS: Prospective, randomized,
      controlled trials comparing 4 days or less of therapy (short courses) with 5 days
      or more of therapy (conventional therapy) were included if all of the subjects
      were <18 years of age, the initial infection was documented by urine culture, at
      least 1 subsequent culture was obtained between 3 and 30 days of enrollment, and
      some attempt was made to separate upper tract from lower tract infection.
      Composite differences among treatment groups were compared with a fixed or random
      effects model, depending on the test for heterogeneity. RESULTS: Of the 517
      citations identified by literature search, 37 were selected for detailed review,
      and 22 were included in the final meta-analysis. The overall difference in cure
      rates between short and conventional courses of therapy was significant (6.38%;
      95% CI: 1.88% to 10.89%), favoring the conventional course. Similar results were
      obtained when only studies comparing the same agents in the short and
      conventional courses were included (7.92%; 95% CI: 2.09% to 13.8%). Short-course
      amoxicillin was inferior to conventional length course (difference in cure rate,
      13%; 95% CI: 4% to 24%); no difference was found between short-course and
      conventional length courses of trimethoprim-sulfamethoxazole (difference in cure
      rate, 6.24%; 95% CI = -3.74% to 16.2%). CONCLUSIONS: We conclude that single-dose
      amoxicillin is inadequate therapy for uncomplicated cystitis of childhood. Three
      days of trimethoprim-sulfamethoxazole therapy appears to be as effective as
      conventional length courses of the drug.

PMID- 11445801
TI  - Helicobacter pylori-associated iron-deficiency anemia in adolescent female
      athletes.
AB  - OBJECTIVE: The objective was to investigate the role of Helicobacter pylori
      infection in iron-deficiency anemia (IDA) of pubescent athletes. STUDY DESIGN:
      Blood sampling and a questionnaire survey were performed on 440 regular high
      school students and 220 athletes of a physical education high school. Hemoglobin,
      serum iron, total iron-binding capacity, ferritin, and immunoglobulin G antibody
      to H. pylori were measured to compare the prevalence of IDA and H. pylori
      infection in the groups. Nutritional analysis and a questionnaire survey for
      socioeconomic status were undertaken to compare and control for other risk
      factors that might influence IDA and H. pylori infection in the groups. In those
      with IDA coexistent with H. pylori infection, we also determined whether IDA can
      be managed by H pylori eradication. RESULTS: The prevalence rates of IDA, H
      pylori infection, and H. pylori -associated IDA in female athletes were higher
      than in the control group. The relative risk of IDA was 2.9 (95% CI, 1.5 to 5.6)
      for those with H. pylori infection. Athletes who exhibited H. pylori -associated
      IDA showed significant increases in hemoglobin, iron, and ferritin levels after
      H. pylori eradication. The subjects in the control group who were treated orally
      with iron alone showed no significant changes. CONCLUSION: Adolescent female
      athletes may have development of H. pylori -associated IDA, which can be managed
      by H. pylori eradication.

PMID- 11445802
TI  - Genotype/phenotype observations in African Americans with Bartter syndrome.
AB  - BACKGROUND: Two Bartter syndrome phenotypes have been described, and molecular
      analyses demonstrate mutations in 1 of 3 genes encoding ascending limb of Henle
      transporters. We report phenotypic observations in 5 African American children
      with Bartter syndrome in the context of a distinct genotype. METHODS: Mutation
      analyses were performed in 5 unrelated African American children with Bartter
      syndrome. These results were correlated to clinical and laboratory data. Calcium
      metabolism was evaluated with a bone disk bioassay. RESULTS: Mutation analyses
      demonstrated homozygous deletion of the ClC-Kb gene in all children. Two children
      had polyhydramnios and premature birth; the others were born at term and
      presented with failure to thrive or dehydration. All receive indomethacin,
      spironolactone, and potassium chloride with improved but borderline hypokalemia.
      Growth has improved with therapy, but height SD scores range from -3.9- to -1.4.
      Urinary calcium excretion is normal, and bone disk bioassay shows no abnormal
      calciotropic activity. No patient had nephrocalcinosis, but renal sonograms show
      loss of corticomedullary differentiation. CONCLUSIONS: African Americans with
      Bartter syndrome genotyped to date have homozygous deletion of ClC-Kb Clinical
      observations in our patients include partial correction of hypokalemia and
      suboptimal growth despite therapy. Abnormal calciotropic activity and
      nephrocalcinosis are not seen, but renal ultrasounds are abnormal.

PMID- 11445803
TI  - Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome.
AB  - OBJECTIVE: The objective was to determine the circadian rhythm of melatonin in
      the Smith-Magenis syndrome (SMS), which causes behavioral problems and sleep
      disturbance. STUDY DESIGN: Questionnaires, sleep consultations, and sleep diaries
      were obtained in 20 children with SMS (9 girls, 11 boys aged 4 to 17 years).
      Actigraphy, electroencephalography, and the circadian variations of plasma
      melatonin, cortisol, and growth hormone were recorded in 8 patients. Early sleep
      onset, early sleep offset, and sleep attack indicated sleep disturbance. RESULTS:
      All children with SMS had a phase shift of their circadian rhythm of melatonin.
      Time at onset of melatonin secretion was 6 AM +/- 2 (control group: 9 P.M. +/-
      2). Peak time was 12 PM +/- 1 (control group: 3:30 AM +/- 1:30), and melatonin
      offset was at 8 PM +/- 1 (control group: 6 AM +/- 1). Behavioral problems
      correlated with the inverted circadian rhythm of melatonin. CONCLUSION:
      Considering that clock genes mediate the generation of circadian rhythms, we
      suggest that haploinsufficiency for a circadian system gene mapping to chromosome
      17p11.2 may cause the inversion of the circadian rhythm of melatonin in SMS.

PMID- 11445804
TI  - The many faces of PHACE syndrome.
AB  - OBJECTIVES: PHACE is an acronym coined to describe a neurocutaneous syndrome
      encompassing the following features: posterior fossa brain malformations, large
      facial hemangiomas, arterial anomalies, cardiac anomalies and aortic coarctation,
      and eye abnormalities. We evaluated the spectrum of disease and significance of
      potential underlying brain anomalies among affected children. STUDY DESIGN: The
      records of 14 patients with PHACE syndrome, evaluated between 1995 and 2000, were
      retrospectively reviewed. A literature review revealed 116 additional cases.
      RESULTS: PHACE syndrome represents a spectrum of anomalies, because most affected
      children have only one extracutaneous manifestation. The syndrome is associated
      with a high incidence of arterial and structural central nervous system anomalies
      with secondary neurologic sequelae. The potential for progressive neurovascular
      disease also exists among those patients with anomalous vasculature. CONCLUSION:
      PHACE syndrome should be considered in any infant presenting with a large,
      segmental, plaque-type facial hemangioma. Children at risk should receive careful
      ophthalmologic, cardiac, and neurologic assessment.

PMID- 11445805
TI  - Hepatosplenomegaly and pulmonary infiltrates in an infant.

PMID- 11445806
TI  - Familial asphyxiating thoracic dysplasia: clinical variability and impact of
      improved neonatal intensive care.
AB  - We describe 3 siblings with asphyxiating thoracic dysplasia whose neonatal
      symptoms range from mild respiratory distress to asphyxia and death. The youngest
      sibling received aggressive modern respiratory intensive care, survived, and at 2
      years showed no respiratory symptoms. Improved neonatal intensive care has
      implications for clinical decision making and genetic counseling.

PMID- 11445807
TI  - Iron-deficient erythropoiesis in premature infants measured by blood zinc
      protoporphyrin/heme.
AB  - We measured red blood cell zinc protoporphyrin/heme (ZnPP/H) ratios in premature
      infants at hospital discharge. ZnPP/heme ratios correlated directly with red
      blood cell distribution width and reticulocyte number. As in other populations,
      ZnPP/H ratios may provide a simple measure of iron-deficient erythropoiesis in
      premature infants.

PMID- 11445808
TI  - Acute hemolysis and severe neonatal hyperbilirubinemia in glucose-6-phosphate
      dehydrogenase-deficient heterozygotes.
AB  - Two premature female infants had severe hyperbilirubinemia caused by hemolysis.
      Both neonates were heterozygotes for the glucose-6-phosphate dehydrogenase
      Mediterranean mutation as determined by DNA analysis. Glucose-6-phosphate
      dehydrogenase-deficient heterozygotes may be susceptible to the complications of
      this enzyme deficiency.

PMID- 11445809
TI  - Clinical features of a human Rac2 mutation: a complex neutrophil dysfunction
      disease.
AB  - The case of an infant with multiple, rapidly progressive, soft-tissue infections
      is presented. Despite features suggesting a neutrophil disorder, results of
      screening tests of phagocyte function were normal. A novel, multifaceted
      leukocyte disorder-distinguished by defects in shape change, chemotaxis,
      ingestion, degranulation, superoxide anion production, and bactericidal activity
      was established secondary to a defect in Rac2.

PMID- 11445810
TI  - A mutation in Bruton's tyrosine kinase as a cause of selective anti
      polysaccharide antibody deficiency.
AB  - Children and adults can have recurrent infection with invasive encapsulated
      bacterial pathogens such as Streptococcus pneumoniae as a result of a selective
      inability to respond to polysaccharide antigens. We have identified a mutation in
      the gene encoding Bruton's tyrosine kinase in a male patient with selective anti
      polysaccharide antibody deficiency.

PMID- 11445811
TI  - The use of alteplase to restore patency of central venous lines in pediatric
      patients: a cohort study.
AB  - We evaluated the efficacy and safety of alteplase to restore central venous line
      (CVL) patency in a consecutive cohort study. A uniform, weight-dependent protocol
      for alteplase administration was established prospectively. For children < or =10
      kg, a dose of 0.5 mg was used; for children >10 kg, doses of 1 to 2 mg were used.
      The alteplase remained instilled for 1 to 4 hours or overnight. Retrospective
      data accrual found that 25 children received alteplase for a total of 34 courses;
      29 (85%) of the 34 courses of alteplase completely restored CVL patency.
      Alteplase appears to be a safe and effective thrombolytic agent for CVL patency
      restoration in children.

PMID- 11445812
TI  - Octreotide for treatment of postoperative chylothorax.
AB  - Two infants who developed chylothorax after surgery for congenital heart disease
      were treated successfully with subcutaneous octreotide. Apart from reducing chyle
      output, octreotide decreased the triglyceride content of the pleural fluid.

PMID- 11445813
TI  - Bacterial colonization of the prepuce in boys with vesicoureteral reflux who
      receive antibiotic prophylaxis.
AB  - Culture swabs were taken from the periurethral area of 59 consecutive
      uncircumcised boys with vesicoureteral reflux (VUR) and 36 boys undergoing
      circumcision. A pure growth of a uropathogen was isolated in 22 (37%) boys with
      VUR who were receiving antibiotic prophylaxis and in 10 (28%) boys who underwent
      circumcision. Antibiotic prophylaxis in patients with VUR was not effective in
      reducing the bacterial colonization of the prepuce. We recommend circumcision in
      boys, particularly infants with VUR, to reduce the risk of urinary tract
      infections.

PMID- 11445814
TI  - Acute gastric dilation and spastic quadriparesis.

PMID- 11445815
TI  - Should pericardial effusion be examined in patients presenting with chylothorax?

PMID- 11445817
TI  - Time to bag the bag.

PMID- 11445819
TI  - Arsenic poisoning caused by Indian ethnic remedies.

PMID- 11445820
TI  - Fulminant hepatic failure in an adolescent.

PMID- 11445822
TI  - Actions of arachidonic acid on contractions and associated electrical activity in
      guinea-pig isolated ventricular myocytes.
AB  - The actions of arachidonic acid (AA) were investigated in guinea-pig isolated
      ventricular myocytes. Exposure of myocytes to 10 microM AA reduced the amplitude
      of contractions and calcium transients accompanying action potentials at a
      frequency of 1 Hz. AA (10 microM) also reduced the amplitude of calcium currents
      recorded under voltage-clamp conditions. The suppression of contraction by AA was
      not prevented by either 10 microM trihydroindomethicin (to inhibit cyclo
      oxygenase) or 10 microM ETYA (5,8,11,14-eicosatetraynoic acid, to inhibit AA
      metabolising enzymes), showing that the actions of AA appeared not to be mediated
      by these metabolites. The reduction of contraction by 10 microM AA was also not
      prevented by the protein kinase C inhibitor, Ro31-8220 (1 microM), showing that
      this pathway appeared not to be required for the observed effect. Direct effects
      of AA may be involved. A further action of 10 microM AA was to suppress
      spontaneous electrical activity induced by either the beta-adrenergic agonist
      isoprenaline or the Na(+) pump inhibitor, ouabain. This effect of AA on
      spontaneous activity might be associated with the observed reduction of calcium
      entry through L-type calcium channels, although additional effects of AA on
      calcium release from the sarcoplasmic reticulum might also be involved.
      Experimental Physiology (2001) 86.4, 437-449.

PMID- 11445823
TI  - EP1 and EP4 receptors mediate exocytosis evoked by prostaglandin E(2) in guinea
      pig antral mucous cells.
AB  - Effects of prostaglandin E(2) (PGE(2)) on exocytosis of mucin were studied in
      mucous cells isolated from guinea-pig antrum using video-microscopy. Stimulation
      with PGE(2) elicited a sustained increase in the frequency of exocytotic events
      in a dose-dependent manner, which was under regulation by both Ca(2+) and cAMP.
      Stimulation with a selective prostanoid EP4 receptor agonist (ONO-AEI-329, 10
      microM), which activates cAMP signals, elicited a sustained increase in the
      frequency of exocytotic events (30 % of that evoked by 1 microM PGE(2)).
      Stimulation with an EP1 agonist (17-P-T-PGE(2), 1 microM), which activates Ca(2+)
      signals, increased the frequency of exocytotic events to a lesser extent (5 % of
      that evoked by 1 microM PGE(2)), while addition of an EP1 antagonist (ONO-8713,
      10 microM) decreased the frequency of exocytotic events (approximately 40 % of
      that evoked by 1 microM PGE(2)). However, addition of the EP1 agonist potentiated
      the frequency of exocytotic events evoked by the EP4 agonist or forskolin (which
      elevates cAMP levels) and increased the sensitivity of the exocytotic events to
      forskolin. These results suggest that the Ca(2+) signal activated via the EP1
      receptor potentiates the cAMP-regulated exocytotic events activated via the EP4
      receptor during PGE(2) stimulation, by increasing the sensitivity of the
      exocytotic response to cAMP. In conclusion, exocytotic events in PGE(2)
      stimulated antral mucous cells were regulated by interactions between EP1 and EP4
      receptors. Experimental Physiology (2001) 86.4, 451-460.

PMID- 11445824
TI  - Interaction between store-operated non-selective cation channels and the Na(+)
      Ca(2+) exchanger during secretion in the rat colon.
AB  - The properties of capacitative Ca(2+) influx were studied using the whole-cell
      patch-clamp technique in crypts isolated from rat distal colon. Store-operated
      cation influx was evoked by increasing the intracellular buffering capacity for
      Ca(2+) in the pipette solution; contamination by Cl(-) currents was reduced by
      the use of NMDG gluconate as the main electrolyte in the pipette solution. The
      permeability of the non-selective cation conductance stimulated by store
      depletion had the following sequence for monovalent cations: Cs(+) > Na(+) > or =
      Li(+). The store-operated conductance is permeable to Na(+) and Ca(2+), but in
      contrast to Na(+), Ca(2+) also exerts a (feedback) inhibition on its own influx.
      Other divalent cations shared this inhibitory action with the sequence: Ca(2+) >
      or = Mg(2+) > or = Ba(2+) > or = Sr(2+). Fura-2 experiments revealed that
      replacement of extracellular Na(+) by NMDG(+) induced an increase in the
      intracellular Ca(2+) concentration, which was suppressed by the Na(+)-Ca(2+)
      exchange inhibitor, dichlorobenzamil, indicating the presence of a Na(+)-Ca(2+)
      exchanger within the colonic crypt cells. In Ussing chamber experiments
      dichlorobenzamil induced an increase in short-circuit current (I(sc)) in the
      majority of tissues tested indicating that this exchanger acts as a Ca(2+)
      extruding transporter under physiological conditions. When Ca(2+)-dependent anion
      secretion was stimulated by the acetylcholine analogue carbachol,
      dichlorobenzamil no longer evoked an increase in I(sc), indicating that after
      stimulation of the store-operated cation conductance the Na(+)-Ca(2+) exchanger
      is turned off. Therefore, it is concluded that the influx of Na(+) across the non
      selective store-operated cation conductance serves to reduce the driving force
      for Ca(2+) extrusion via the Na(+)-Ca(2+) exchanger and thereby maintains the
      increase in the intracellular Ca(2+) concentration during induction of secretion.
      Experimental Physiology (2001) 86.4, 461-468.

PMID- 11445825
TI  - Effects of the potassium channel blocker barium on sodium and potassium transport
      in the rat loop of Henle in vivo.
AB  - In vitro evidence suggests that the 'recycling' of K(+) ions through luminal K(+)
      channels in the thick ascending limb of the loop of Henle (TALH) is essential for
      the normal operation of the luminal Na(+)-K(+)-2Cl(-) co-transporter. In the
      present study these channels were investigated in vivo by perfusing superficial
      loops of Henle in anaesthetised rats with and without the K(+) channel blocker
      barium. Using a standard perfusate, intraluminal barium (5 mmol l(-1)) reduced
      sodium reabsorption (J(Na)) from 1887 +/- 50 to 1319 +/- 53 pmol min(-1) (P <
      0.001). When the experiment was repeated using a low-Na(+) perfusate, designed to
      inhibit reabsorption in the pars recta (the initial segment of the loop of
      Henle), a similar reduction in J(Na) was observed (from 698 +/- 47 to 149 +/- 23
      pmol min(-1), P < 0.001), strongly suggesting that the effect of barium is
      localised to the TALH. The magnitude of the reduction in J(Na) during blockade of
      K(+) channels confirms the importance of K(+) recycling in facilitating Na(+)
      reabsorption in the TALH in vivo. However, the reduction in J(Na) was not
      associated with a fall in the K(+) concentration of the fluid collected at the
      early distal tubule. When bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co
      transporter, was included in the low-Na(+) perfusate, net K(+) secretion was
      observed. Addition of barium to this perfusate reduced, but did not abolish, the
      secretion, suggesting that bumetanide-induced K(+) secretion results partly from
      paracellular transport. Experimental Physiology (2001) 86.4, 469-474.

PMID- 11445826
TI  - Gustatory-salivary reflexes induce non-adrenergic, non-cholinergic acinar
      degranulation in the rat parotid gland.
AB  - In the presence of the muscarinic blocker atropine, the alpha-adrenoceptor
      blocker phentolamine and the beta-adrenoceptor blocker propranolol (2 mg kg(-1)
      of each, I.P.), the numerical density of parotid acinar secretory granules was
      reduced by 32 % in response to ascorbic acid (0.5 M) applied on the tongue every
      30 s over 30 min in awake rats. This non-adrenergic, non-cholinergic (NANC)
      response was entirely dependent on an intact auriculo-temporal nerve supply. The
      NANC mechanisms were found to be potentially responsible for almost all of the
      exocytotic response that occurs in the absence of the three autonomic receptor
      blockers. No sympathetic contribution to the exocytotic response was found and
      furthermore, studies in parasympathetically denervated glands showed that the
      sympathetic contribution to the salivary flow was small. Experimental Physiology
      (2001) 86.4, 475-480.

PMID- 11445827
TI  - Contribution of endothelial nitric oxide synthase in the blunted renal responses
      to volume expansion in diabetic rats.
AB  - The renal excretory responses to volume expansion (VE), by 10 % body wt, were
      determined in groups of anaesthetised streptozotocin-induced diabetic rats with
      one denervated and one innervated kidney in the presence and absence of nitric
      oxide synthase (NOS) inhibitors. VE in diabetic rats increased (P < 0.001)
      cumulative urine sodium excretion (CuU(Na)V) to 104 +/- 9 and 69 +/- 6 micromol
      min(-1) (g kidney wt)(-1) in the denervated and in the innervated kidneys,
      respectively, which were both less (P < 0.001) than in the non-diabetic rats, at
      225 +/- 14 and 148 +/- 14 micromol min(-1) (g kidney wt)(-1), respectively, in
      the denervated and the innervated kidney. The non-selective NOS inhibitor, N(G)
      nitro-L-arginine-methyl-ester (L-NAME) given to the diabetic rats with intact
      renal innervation enhanced CuU(Na)V after VE by 43 % (P < 0.001), while the
      combination of L-NAME and renal denervation restored CuU(Na)V to a value
      comparable to that of non-diabetic rats. In diabetic rats treated with either a
      relatively selective inhibitor for the neuronal isoform of NOS, 7-nitroindazole,
      or a relatively selective inhibitor for the inducible isoform of NOS,
      aminoguanidine, CuU(Na)V after VE was similar to the untreated diabetic rats
      irrespective of whether or not the renal nerves were present. This investigation
      demonstrated that NO production contributed, at least partly, to the depressed
      ability to excrete a saline load in diabetes mellitus. The endothelial isoform of
      NOS was most probably responsible for generating NO which caused the blunted
      excretory responses. The ability of NO to attenuate the excretory responses to
      volume expansion was an action independent of the renal innervation status.
      Experimental Physiology (2001) 86.4, 481-488.

PMID- 11445828
TI  - Sapid solutions and food intake in repeated dehydration and rehydration periods
      in rats.
AB  - In a previous report, it has been shown that water deprivation significantly
      affects the two-bottle taste preferences and one-bottle taste acceptance in rats
      when no food was available during tests. Since no food was available, the course
      of drinking was never interrupted by eating. Theoretically, if a rat faces a
      simultaneous choice between food and fluid, and if the course of drinking is
      interrupted by eating, these conditions might interfere with taste preferences,
      total fluid intake and eating in thirsty rats. The aims of the present
      experiments were: to ascertain whether food intake during both two-bottle
      preference and one-bottle acceptance tests in thirsty rats might be influenced by
      the palatability of the solutions; to verify whether the availability of food
      during tests influences taste preference and acceptance, and total fluid intake;
      to detect variations induced by dehydration on body weight and some plasma and
      urinary parameters that might interfere with food and fluid intake, taste
      preference and acceptance. Using naive rats, five groups of rats showing the same
      taste preferences for one of four prototypical tastes and water were selected.
      Then, both two-bottle preference (Expt 1) and one-bottle acceptance tests (Expt
      2) were performed in rats deprived of water for either 12, 24, 36 or 48 h. The
      results showed that in both Expt 1 and Expt 2, inhibition of feeding and decrease
      of body weight during dehydration was very similar in all rats. The presence of
      food during the tests did not affect taste preference and acceptance. During Expt
      1, after severe water deprivation (36 and 48 h), food intake was related to the
      palatability of the solution paired with water. When rats drank either NaCl or
      sucrose, they ate less food than rats drinking HCl, quinine, or water. In Expt 2,
      rats drinking NaCl solution as the only source of fluid ate significantly less
      food than all other groups. The intake of sucrose and/or NaCl solutions be may
      explained by two different post-ingestion effects (energetic and osmotic). Since
      rats drinking either sucrose or NaCl ate less food but drank more fluid, they had
      a significantly higher fluid/food intake ratio than that of rats who drank water,
      quinine, or HCl, who ate more food but drank less fluid. The increase of the
      fluid/food intake ratio in rats drinking sucrose or NaCl was directly correlated
      with the length of dehydration. Self-denial of food during dehydration may be
      responsible for overeating and overdrinking during the recovery period after
      tests. After dehydration lasting for 24 and 48 h, plasma [Na(+)], [protein],
      osmolality and haematocrit values increased but [K(+)] decreased. Urinary volume
      decreased but urinary [Na(+)] increased. These results are related to food and
      fluid intake, taste preference and acceptance after dehydration periods.
      Experimental Physiology (2001) 86.4, 489-498.

PMID- 11445829
TI  - Interaction of diet and training on endurance performance in rats.
AB  - We determined the interaction of diet and training on metabolic adaptations in
      skeletal muscle and liver, and the consequences of these adaptations for
      endurance. Eighty rats performed a baseline treadmill run to exhaustion at 16 m
      min(-1) (RUN1) and were then divided into two groups and given one of two diets:
      high carbohydrate (CHO) or high fat (FAT). Each dietary group was then divided
      into one of four subgroups: sedentary control that performed no training (NT);
      low-intensity running (8 m min(-1); LOW) and two groups who trained at their
      maximal voluntary running speed without electrical stimulation (28 m min(-1);
      VMAX). Training volume was identical for LOW and VMAX (1000 m session(-1)) and
      animals ran 4 days week(-1) for 8 weeks. To assess the interaction of the higher
      intensity exercise with diet, a second endurance test (RUN2) was undertaken after
      6 weeks at either 16 m min(-1) or 28 m min(-1). The NT group ran for a longer
      duration (increase of 77 %) after FAT than CHO (239 +/- 28 vs. 135 +/- 30 min, P
      < 0.05) at 16 m min(-1). There were no differences in RUN2 for the LOW group when
      rats ran at 16 m min(-1) (454 +/- 86 vs. 427 +/- 75 min for CHO and FAT groups,
      respectively), but rats in the VMAX group fed FAT ran longer than rats fed CHO at
      28 m min(-1) (100 +/- 28 vs. 58 +/- 11 min, respectively, P < 0.05). FAT
      increased the activities of the enzymes citrate synthase, beta-hydroxyacyl-CoA
      dehydrogenase and carnitine palmitoyl-transferase compared to CHO (P < 0.01), but
      there was no systematic effect of training. We conclude: (1) there was no
      additive effect of a high-fat diet on endurance performance when rats performed
      low-intensity training; (2) running performance at 28 m min(-1) was only enhanced
      by a high-fat diet after more intense training; (3) diet-induced and training
      induced adaptations that increase exercise capacity may be under independent
      control. Experimental Physiology (2001) 86.4, 499-508.

PMID- 11445830
TI  - The effects of age and hindlimb supension on the levels of expression of the
      myogenic regulatory factors MyoD and myogenin in rat fast and slow skeletal
      muscles.
AB  - In this study we tested the hypothesis that, compared to young adult rats,
      senescent rats have a reduced ability to respond to muscle unloading. Unloading
      of the muscles was induced by hindlimb suspension (HS) of young adult and
      senescent rats for 21 days. Plantaris muscles from young adult rats had
      significantly higher levels of myogenin mRNA and protein (890 % and 314 %,
      respectively, P < 0.05) than plantaris muscles from senescent rats and also a
      higher MyoD mRNA level (280 %, P < 0.05), but ageing did not increase MyoD
      protein levels. Although HS did not increase plantaris mRNA or protein levels of
      myogenin or MyoD in senescent rats (P = 0.22), myogenin mRNA and protein levels
      increased by 850 % and 580 % respectively, and MyoD mRNA and protein levels by
      235 % and 1600 %, respectively in young adult rats (P < 0.05). Soleus muscles
      from senescent rats had 150 % and 85 % greater myogenin and MyoD mRNA levels,
      respectively (P < 0.05), than soleus muscles from young adult rats, whereas
      protein levels of myogenin were similar (P > 0.05) and MyoD protein levels were
      60 % lower in the muscle of senescent rats (P < 0.05). In young rats, soleus
      muscle mRNA levels of myogenin and MyoD were not altered by HS but myogenin
      protein levels decreased by 57 % (P < 0.05) whereas MyoD protein levels increased
      by 187 % (P < 0.05). In senescent rats, HS decreased soleus muscle myogenin mRNA
      and protein levels by 42 % and 26 % respectively (P < 0.05), but MyoD protein and
      mRNA levels were not changed. MRF4 levels were not affected by ageing in either
      muscle. These data suggest that ageing reduces the ability of fast muscles to
      increase myogenin protein levels, and prevents both fast and slow muscles from
      increasing MyoD protein levels during muscle unloading. Experimental Physiology
      (2001) 86.4, 509-517.

PMID- 11445831
TI  - Identification of arterial wall dynamics in conscious dogs.
AB  - Viscoelastic properties determine the dynamic behaviour of the arterial wall
      under pulsatile pressure and flow, suggesting time- or frequency-dependent
      responses to changes in wall stress and strain. The objectives of the present
      study were: (i) to develop a simplified model to derive simultaneously the
      elastic, viscous and inertial wall moduli; (ii) to assess Young's modulus as a
      function of frequency, in conscious, chronically instrumented dogs. Parametric
      discrete time models were used to characterise the dynamics of the arterial
      system based on thoracic aortic pressure (microtransducer) and diameter
      (sonomicrometry) measurements in control steady state and during activation of
      smooth muscle with the alpha-adrenoceptor agonist phenylephrine (5 microg kg(-1)
      min(-1), I.V.), in eight conscious dogs. The linear autoregressive model and a
      physically motivated non-linear model were fitted to the input-output (stress
      strain) relationship. The aortic buffering function (complex Young's modulus) was
      obtained in vivo from the identified linear model. Elastic, viscous and inertial
      moduli were significantly increased from control state ((44.5 +/- 7.7) x 10(4)
      Pa; (12.3 +/- 4.7) x 10(4) Pa s; (0.048 +/- 0.028) x 10(4) Pa s(2) ) to active
      state ((85.3 +/- 29.5) x 10(4) Pa, P < 0.001; (22.4 +/- 8.3) x 10(4) Pa s, P <
      0.05; (0.148 +/- 0.060) x 10(4) Pa s(2), P < 0.05). These moduli, obtained using
      the linear model, did not present significant differences compared with those
      derived using the non-linear model. In control conditions, the magnitude of the
      normalised complex Young's modulus was found to be similar to that reported in
      previous animal studies ranging from 1 to 10 Hz. During vascular smooth muscle
      activation, this modulus was found to be increased with regard to control
      conditions (P < 0.01) in the frequency range used in this study. The frequency
      dependent Young's modulus of the aortic wall was obtained for the first time in
      conscious, unsedated dogs. The parametric modelling approach allows us to verify
      that vascular smooth muscle activation increases the elastic, viscous and
      inertial moduli with the advantage of being able to track their time evolution.
      Furthermore, under activation, the aortic wall remains stiff in the physiological
      frequency range, suggesting the impairment of the arterial buffering function.
      Experimental Physiology (2001) 86.4, 519-528.

PMID- 11445832
TI  - Effects of 8 h of isocapnic hypoxia with and without muscarinic blockade on
      ventilation and heart rate in humans.
AB  - This study examined the role of muscarinic parasympathetic mechanisms in
      generating the progressive increases in ventilation (V(E)) and heart rate
      previously reported with 8 h exposures to hypoxia. The sensitivities of V(E)
      (G(p)) and heart rate (G(HR)) to acute variations in hypoxia, and V(E) and heart
      rate during acute hyperoxia were assessed in 10 subjects before and after two 8 h
      exposures to isocapnic hypoxia (end-tidal P(O2) = 50 mmHg). The responses were
      measured during muscarinic blockade with glycopyrrolate (0.015 mg kg(-1)) and
      without glycopyrrolate, as a control. There were significant increases in G(p) (P
      < 0.01) and V(E) during hyperoxia (P < 0.01) following hypoxic exposure, but
      these were unaffected by glycopyrrolate. G(HR) increased significantly by 0.29 +/
      0.08 beats min(-1) %(-1) (mean +/- S.E.M.) following exposure to hypoxia under
      control conditions, but only non-significantly by 0.10 +/- 0.08 beats min(-1) %(
      1) with glycopyrrolate. This difference was significant. Changes in heart rate
      during hyperoxia were slight and inconclusive. We conclude that muscarinic
      mechanisms play little role in the progressive ventilatory changes that occur
      over 8 h of hypoxia, but that they do mediate much of the progressive increase in
      heart rate. Experimental Physiology (2001) 86.4, 529-538.

PMID- 11445833
TI  - Reduced glutathione system: role in cancer development, prevention and treatment
      (review).
AB  - Reduced glutathione (GSH), a ubiquitous thiol-containing tripeptide, is
      unanimously recognized to play a central role in cell biology. It is highly
      implicated in the cellular defense against xenobiotics and naturally occurring
      deleterious compounds such as free radicals and hydroperoxides. Consequently, GSH
      is an essential actor in several human diseases including cancer and cardio
      vascular diseases. Its implication in oncogenesis has led to the development of
      new strategies to improve both prevention and treatment of cancer. The present
      review proposes an in depth analysis or our current knowledge of the relations
      between GSH and cancer.

PMID- 11445834
TI  - The molecular effects of oncogenesis on cell-extracellular matrix adhesion
      (review).
AB  - Cell-extracellular matrix adhesive interactions provide a key regulatory mode of
      cellular behavior. The molecular basis of adhesion-mediated signaling responses
      has been under investigation over the past few years. Tyrosine phosphorylation
      initiated by cell adhesion plays a crucial role in regulating adhesion-mediated
      signaling and cytoskeletal rearrangement. Oncogenesis involves aberrant
      interactions between cells and the extracellular matrix. The mechanisms that
      underline the functions of oncogenes and tumor suppressors often involve
      modulation of specific tyrosine phosphorylated cytoplasmic proteins, thereby
      affecting directly adhesion-mediated signaling. The constitutive kinase activity
      of oncogenes such as v-Src and BCR/Abl hyper-phosphorylates cytoskeletal and
      signaling molecules, and modulates the functions of integrins, the predominant
      family of extracellular matrix receptors. The tumor suppressor gene PTEN was
      recently identified as a key regulator of adhesion-mediated signaling. This
      review summarizes the direct effects of oncogenes, tumor suppressor genes and
      their products on the adhesive responses of cells. Understanding of the molecular
      basis of these effects may provide the means to develop novel therapeutics to
      control pathological processes associated with aberrant cell-extracellular matrix
      interactions.

PMID- 11445835
TI  - Importance of cell proliferative state and potentially lethal damage repair on
      radiation effectiveness: implications for combined tumor treatments (review).
AB  - The dependence of parameters of the linear-quadratic (LQ) model on cell
      proliferation kinetics of tumors in relation to potentially lethal damage (PLD)
      and its repair is evaluated. The influence of sensitizing agents on these
      parameters during fractionated radiotherapy is assessed. Suggestions for
      scheduling of radiation combined of with sensitizing agents are derived. The
      parameters alpha and beta of the linear-quadratic model for dose dependence of
      cell reproductive inactivation, derived from experimental and clinical data, are
      evaluated to assess their dependence on cell proliferative state, on PLD repair
      and on the action of various sensitizing agents. PLD contributes to the linear as
      well as to the quadratic component of the LQ model. PLD is less effectively
      repaired in proliferating (P) cells than in clonogenic (G0) cells of the
      quiescent (Q) cell compartment. PLD is influenced by various agents applied
      during, as well as after irradiation. The parameters alpha and beta are affected
      differently by the proliferative state of cells, by some of the sensitizing
      agents, and by radiation quality. The relative fractions of P cells and Q cells
      can change during fractionated treatments. If recruitment is effective, the
      fraction of G0 cells decreases in the latter part of a treatment schedule. PLD
      from subsequent radiation doses is then repaired less and the effectiveness of
      radiation combined with sensitizing agents may be enhanced. The analyses using
      the LQ model show differences in PLD and its repair between P cells and G0 cells
      in tumors. If due to recruitment the compartment of clonogenic G0 cells
      diminishes during treatment, the combination of radiation with sensitizing agents
      and the application of high-LET radiation should be scheduled to take this factor
      into account. For poorly differentiated tumors with high labeling indices (LI),
      benefit from combined treatments is expected from early in the course of
      fractionated radiotherapy. Well differentiated tumors with low LI are suggested
      to benefit most from irradiation combined with sensitizing agents in the latter
      part of a treatment schedule. New methods are required to assess the clonogenic
      G0 cells in the Q cell compartment and to monitor recruitment of these cells into
      the P cell compartment.

PMID- 11445836
TI  - Hypoxia-inducible factor: Achilles' heel of antiangiogenic cancer therapy
      (review).
AB  - Could a rational, hypothesis-driven and well-tolerated therapy drive tumor
      progression? This scenario can be foreseen for antiangiogenic therapy, despite it
      is one of the most elegant anticancer strategies. Antiangiogenic agents inhibit
      growth of endothelial cells resulting in tumor hypoxia and starvation which in
      turn inhibit tumor growth. On the other hand, it is known that hypoxia selects
      for a highly aggressive and metastatic cancer and is associated with unfavorable
      prognosis. This review attempts to reconcile these opposite notions and to
      revisit the thesis that antiangiogenic therapy is "resistant to resistance". The
      latter logical paradigm is based on the notion that endothelial cells cannot
      become drug resistant. Although endothelial cells may not acquire drug
      resistance, cancer cells can acquire hypoxia-resistance which is also associated
      with the resistance to growth arrest and apoptosis as well as high metastatic
      potentials. Hypoxia-inducible factor (HIF-1) renders cells capable of surviving
      hypoxia and stimulating endothelial growth. Disruption of the HIF-1 pathway
      inhibits tumor growth, indicating HIF-1 as a potential anticancer target.
      Furthermore, inhibition of HIF-1 is a mechanism-based antiangiogenic strategy
      because it is the HIF-mediated response that drives tumor angiogenesis.
      Pharmacological approaches to HIF-1 inhibition are discussed.

PMID- 11445837
TI  - Induction of mammary epithelial cell differentiation and inhibition of
      dimethylbenz(A)anthracene-induced mammary tumour by co-administration of a pure
      antiestrogen ICI 182,780 and testosterone enanthate.
AB  - Epidemiological studies have shown that early first pregnancy is associated with
      a life-long reduction in breast cancer risk. The terminal differentiation
      associated with pregnancy and lactation has been proposed as a mechanism
      underlying the protective effect of pregnancy. We report that treatment of rats
      with ICI 182,780 (ICI) caused a marked reduction in epithelial cells and Ki-67
      labelling index as compared to controls and testosterone enanthate-treated (TE)
      mammary glands. TE increased the Ki-67 labelling index, stimulated lobuloalveolar
      and ductal growth, as well as the secretory activity of acinar cells. Co
      administration of TE and ICI resulted in a reduction in Ki-67 labelling index.
      Mammary epithelial cells became differentiated, resembling that observed at the
      end of pregnancy and during lactation as indicated by marked increase in
      secretory activity, lipid accumulation and presence of basal nuclei. The
      expression of differentiation markers such as whey acidic protein, mammary
      derived growth inhibitor, alpha-casein and beta-casein was detected only in TE
      plus ICI treated mammary tissues. Unlike TE, ICI caused a significant reduction
      in DMBA-induced tumour incidence, number of tumour bearing and tumour size.
      Tumour incidence was reduced to 8% when both ICI and TE were co-administered. Our
      data provide the novel molecular interactions between the estrogen and androgen
      in regulation of mammary growth and differentiation. These observations may give
      insight into novel actions of ICI and TE on breast differentiation and protection
      against carcinogenesis which may be useful in designing novel strategies for
      cancer prevention and/or treatment based on maximizing mammary epithelial cell
      differentiation.

PMID- 11445838
TI  - p73 is highly expressed in myoepithelial cells and in carcinomas with metaplasia.
AB  - p73, a homologue of p53 gene, is expressed in several normal tissues including
      central nervous system, but data regarding tumors are scant. In this study, we
      have analyzed the status and expression of the p73 gene in primary breast tumors,
      as well as 4 normal salivary glands, 2 carcinomas with metaplasia and mixed
      tumors. We found that periductal myoepithelial cells of all of the mammary gland
      examined were clearly stained with the specific anti-p73 antibody. Furthermore,
      we found the expression of p73 in the neoplastic myoepithelial cells in
      carcinomas with metaplasia and in mixed tumors. The findings in the present study
      provide valuable information on the characteristics of myoepithelial cells.

PMID- 11445839
TI  - Hypermethylation of p16(INK4a) and p15(INK4b) genes in non-small cell lung
      cancer.
AB  - Hypermethylation of CpG island is a common mechanism by which tumor suppressor
      genes are inactivated. The tumor suppressor genes p16(INK4a) and p15(INK4b) are
      important components of the cell cycles. We have studied the feasibility of
      detecting tumor-associated aberrant p16(INK4a) and p15(INK4b) methylation in non
      small cell lung cancer (NSCLC) using methylation-specific PCR. We found a high
      frequency of hypermethylation of the p16(INK4a) gene in 17 of 45 cases of NSCLC.
      In this study, there was no difference between the clinicopathological features
      or overall survival of patients with and without p16(INK4a) methylation. On the
      other hand, p15(INK4b) promoter hypermethylation is rare (5/45) in lung cancer
      and occurs in association with p16(INK4a) methylation. The overall survival of
      patients with p15(INK4b) methylation was markedly shortened in this series. We
      also analyzed cells in bronchial washings, and p16(INK4a) methylation was
      detected in 4 of 17 cases of NSCLC. Moreover, 1 of 10 plasma samples from
      patients with NSCLC was positive for p16(INK4a) methylation. Our results suggest
      a possible prognostic role of p15(INK4b) methylation in NSCLC, and that the
      detection of aberrant p16(INK4a) methylation in both bronchial washings and
      plasma may be useful for cancer diagnosis.

PMID- 11445840
TI  - Bcl10 expression, rearrangement and mutation in MALT lymphoma: correlation with
      expression of nuclear factor-kappaB.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphomas usually involve extranodal
      sites, especially the stomach, lung and salivary glands. The Bcl10 gene was
      recently isolated from the breakpoint region of t(1;14) (p22;q32) in MALT
      lymphomas, and considered to be an apoptosis-associated gene, and involves a
      caspase recruitment domain (CARD)-containing protein that activates NF-kappaB. We
      investigated the role of Bcl10 in MALT lymphoma by analyzing its expression,
      rearrangement and somatic mutation, by immunostaining, reverse transcriptase
      polymerase chain reaction (RT-PCR), Southern blot and PCR in 20 cases of MALT
      lymphoma. Expression of NF-kappaB was studied by immunostaining. Five cases of
      reactive lymphadenitis (RLA) were used as the control. Bcl10 rearrangement was
      detected in 8 of 20 (40%) MALT lymphomas, but in none of RLA. Significant Bcl10
      mutation was detected only in 1 case (5%) with MALT, but not in RLA. RT-PCR
      showed higher density bands of Bcl10 in MALT lymphomas than in RLA.
      Immunostaining showed a weak Bcl10 expression in the germinal center and very
      weak expression in the marginal zone B-cells in RLA, which was limited to the
      cytoplasm. In contrast, Bcl10 was strongly expressed in MALT lymphomas, and was
      mainly detected in the cytoplasm, as well as in the nuclei. Bcl10 expression did
      not correlate with Bcl10 mutation and re-arrangements. NF-kappaB was expressed in
      nuclei of MALT lymphoma cells, but not in RLA. Bcl10 expression in MALT lymphoma
      correlated closely with NF-kappaB expression. Our results suggest that activation
      of Bcl10 and NF-kappaB may be important in MALT lymphomagenesis, and that nuclear
      localization of Bcl10 may be important in the progression of MALT.

PMID- 11445841
TI  - Optimal duration of oral adjuvant chemotherapy with Carmofur in the colorectal
      cancer patients: the Kansai Carmofur Study Group trial III.
AB  - A multi-institutional study was performed to evaluate the appropriate duration of
      oral administration of Carmofur (1-hexylcarbamoyl-5-fluorouracil, HCFU), a 5
      fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in
      patients with colorectal cancer undergoing curative operation. Patients were
      divided into two: i) short duration group receiving 6 months of HCFU
      administration and ii) long duration group receiving 1 year of the
      administration, using a centralized registration system. Among 364 patients
      entered in this study, 293 evaluable cases were analyzed to investigate the
      appropriate duration of adjuvant oral chemotherapy. No statistical differences
      were found in the cumulative 5-year disease-free or survival rates between the
      groups. However, the actual duration of oral HCFU administration differed in the
      patients of short and long duration groups from the protocol. Namely, more than
      70% of the patients received a different duration of oral adjuvant chemotherapy
      in each of the groups. Therefore, apart from this division of two groups,
      correlation between the actual duration of oral HCFU administration and the
      prognosis was examined in these patients. As a result, it was suggested that oral
      adjuvant chemotherapy with HCFU would be effective in colon cancer patients when
      the duration of administration exceeded 330 days. In rectal cancer patients,
      however, adjuvant chemotherapy with HCFU alone was considered to be not
      sufficient to affect the prognosis.

PMID- 11445842
TI  - Selective apoptosis induction in transformed fibroblasts by B cell lines:
      involvement of reactive oxygen and nitrogen species.
AB  - B cell lines induce apoptosis selectively in transformed fibroblasts. Apoptosis
      induction is independent of direct cell contact. It seems to be based on
      superoxide anion production by transformed cells, subsequent spontaneous
      dismutation to hydrogen peroxide and utilization of the hydrogen peroxide by a
      peroxidase released by effector cells. The peroxidase then generates hypochlorous
      acid which may interact with target cell derived superoxide anions, yielding
      apoptosis-inducing hydroxyl radicals. In parallel, NO released by effector cells
      may interact with target cell derived superoxide anions and generate the
      apoptosis inducer peroxynitrite. Therefore, in parallel to their specific
      functions in humoral immunity, B cells seem to have the potential to contribute
      to those signalling pathways directed against transformed cells that have been
      recently shown to be established by TGF-beta treated fibroblasts. This
      intercellular signalling system seems to represent an evolutionary ancient system
      for the control of cells that potentially endanger the survival of multicellular
      organisms.

PMID- 11445843
TI  - Thrombospondin-1 and -2 messenger RNA expression in normal and neoplastic
      endometrial tissues: correlation with angiogenesis and prognosis.
AB  - The role of thrombospondin (TSP) in tumor angiogenesis and progression remains
      controversial. The expression of TSP-1 and TSP-2 mRNAs was assessed. Furthermore,
      TSP association with clinicopathological features, including microvessel count,
      regarding prognostic significance was examined. Expression of TSP-1 and TSP-2
      were assessed by reverse transcriptase-polymerase chain reaction in 18 normal
      endometrium and 55 endometrial cancer samples. Microvessel counts were determined
      by immunostaining for factor VIII-related antigen in endometrial cancer
      specimens. TSP-1 expression of secretory phase endometrium was markedly higher
      than that of proliferative phase endometrium (p=0.047). Expression of TSP-1 and
      TSP-2 was detected in 33 (60.0%) and 15 cases (27.3%), respectively, of 55
      endometrial cancer samples. TSP-1 expression was significantly higher in tumors
      recovered from elderly women (p=0.009). TSP-2 expression was significantly higher
      in malignancies exhibiting cervical and lymph-vascular space involvement (p=0.029
      and p=0.009, respectively). Although not statistically significant, microvessel
      counts were higher in cases displaying increased TSP-1 expression. The
      microvessel count in patients with TSP-2 expression was markedly higher than that
      observed in patients lacking TSP-2 expression (p=0.026). Subjects demonstrating
      TSP-2 mRNA expression displayed significantly poorer prognosis than those lacking
      TSP-2 mRNA expression (p=0.016). There was no association between TSP-1 mRNA
      expression and patient outcome. Our findings provide evidence that elevated TSP
      expression may be associated with an angiogenic phenotype in endometrial cancer.
      In addition, TSP-2 expression is a marker for poor prognosis in this disease.

PMID- 11445844
TI  - FRAT1 and FRAT2, clustered in human chromosome 10q24.1 region, are up-regulated
      in gastric cancer.
AB  - FRAT1 and FRAT2 are cancer-associated genes encoding GSK-3beta-binding proteins.
      Over-expression of FRAT1 or FRAT2 lead to carcinogenesis through activation of
      WNT--beta-catenin--TCF signaling pathway. We have previously cloned and
      characterized FRAT2. Here, we found that FRAT1 and FRAT2 genes were clustered in
      the human chromosome 10q24.1 region. Blast search revealed that FRAT1 and FRAT2
      genes, consisting of a single exon, were located together on human genome draft
      sequences AC006098.1 and AL355490.7, corresponding to the human chromosome
      10q24.1 region. FRAT1 and FRAT2 genes were clustered in a tail to tail manner
      with an interval of about 10.7 kb. The 2.7-kb FRAT1 mRNA was relatively highly
      expressed in fetal brain, adult spleen, pancreas, HeLa S3 (cervical cancer), and
      K-562 (chronic myelogenous leukemia). FRAT1 and FRAT2 were co-expressed in 7
      gastric cancer cell lines and 10 cases of primary gastric cancer, and were up
      regulated together in gastric cancer cell line TMK1 and 2 cases of primary
      gastric cancer. These results indicated that FRAT1 and FRAT2 genes were up
      regulated together in several cases of human gastric cancer. Up-regulation of
      FRAT1 and FRAT2 in gastric cancer might lead to carcinogenesis through activation
      of WNT--beta-catenin--TCF signaling pathway.

PMID- 11445845
TI  - S-adenosylmethionine decarboxylase overexpression reduces invasiveness and
      tumorigenicity in nude mice of MCF-7 breast cancer cells.
AB  - To elucidate the role of S-adenosylmethionine decarboxylase (SAMDC) in breast
      cancer biology, we have generated SAMDC overexpressing MCF-7 breast cancer cells.
      SAMDC overexpression did not alter in a major way growth properties of MCF-7
      cells in soft agar, either under basal conditions or in response to estrogen and
      antiestrogen administration. SAMDC-MCF-7 cells, on the other hand, exhibited a
      markedly reduced invasive ability in matrigel (p=0.013). Furthermore, they were
      less tumorigenic in nude mice. The odds for control clones to form tumors were
      3.13 (C.1.1.2-8.2, p=0.0184) higher than those for SAMDC clones. The odds ratio
      were identical in the absence and in the presence of estradiol. In addition, the
      growth rate of established tumors was slower for SAMDC than for control clones.
      Overall, our results are consistent with the notion that these phenotypic changes
      induced by SAMDC overexpression are primarily mediated by suppression of cellular
      putrescine (and, possibly, spermidine) levels.

PMID- 11445846
TI  - Effect of cyclic plasma perfusion on apoptosis regulatory proteins in primary
      tumors of VX2-carcinoma-bearing rabbits.
AB  - Although the mechanism of cancer cachexia is unknown, in previous studies we
      reported that cyclic plasma perfusion through non-coated charcoal was effective
      in preventing cancer cachexia. In the present study we investigated the effect of
      cyclic plasma perfusion on VX2 carcinoma. Sixteen tumor-bearing rabbits were
      divided into two groups: i) a group subjected to cyclic plasma perfusion (n=8,
      group PP) and ii) a group subjected to sham-perfusion (n=8, group SP), and
      changes in body weight, tumor size, and morphological findings were investigated.
      Body weight loss and tumor growth were significantly suppressed in group PP. The
      tumor cells in group PP showed apoptosis and a high Bax/Bcl-2 ratio, and the
      survival rate was significantly higher than in group SP. These results suggest
      that cyclic plasma perfusion is effective not only in preventing cancer cachexia
      but in suppressing tumor growth and improving outcome.

PMID- 11445847
TI  - The relationship between allelic imbalance on 17p, p53 mutation and p53
      overexpression in head and neck cancer.
AB  - The huge majority of head and neck squamous cell carcinoma (HNSCC) show
      alterations of p53 either on the genetic level or on the protein level. Allelic
      imbalance (AI)/loss of heterozygosity (LOH) on 17p at the p53 locus is frequent
      in HNSCC. However, the complex relationship between these phenomena is poorly
      understood in HNSCC. We investigated one group of 39 HNSCC for: a) allelic
      imbalance on 17p using 4 microsatellite markers located throughout this
      chromosomal arm; b) mutations of p53 in exons 5-9; and c) overexpression of p53
      using two antibodies located on opposite ends of the protein. AI/LOH was detected
      in 44% at the locus TP53, rising to 69% when regarding all 4 markers on 17p.
      Therefore, our data are in line with the assumption of additional tumour
      suppressor genes on 17p in HNSCC. A nuclear accumulation of p53 (51%) was
      independent from the antibody and the recognised epitope. At the first glance
      there was no correlation between overall p53 mutation (36%) and overexpression.
      However, it appeared that, with very few exceptions, only nonsense mutations did
      not lead to p53 overexpression, while missense mutations did. As overexpression
      of p53 was 15% more frequent than p53 mutations and only 35% of the tumours with
      p53 overexpression carried a p53 mutation, our data support the hypothesis of
      additional mechanisms of p53 overexpression. AI/LOH at the p53 locus in 83% of
      all tumours with a p53 mutation is in line with Knudson's theory of inactivation
      of tumour suppressor genes.

PMID- 11445848
TI  - "Variable echo sign" (ultrasonographical alteration of echogenicity) in cavernous
      hepatic hemangioma.
AB  - There are few reports describing cavernous hepatic hemangiomas with alteration of
      ultrasonographical imaging during examinations. We performed ultrasonographic
      examination of 64 cavernous hepatic hemangiomas and recognized 26 cases (41%)
      with an alteration of echogenicity during the examinations. We refer to this
      alteration of echogenicity of cavernous hepatic hemangioma as a "variable echo
      sign". We performed angiography of the cavernous hepatic hemangiomas with
      variable echo sign. Most of these imaging patterns showed mild or moderate
      pooling, suggesting that the alteration of echogenicity might be based on a slow
      blood flow exchange. We suggest that a variable echo sign is specific to
      ultrasonographic imaging with cavernous hepatic hemangioma and may be useful to
      differentiate cavernous hepatic hemangioma from other tumors.

PMID- 11445849
TI  - Changes in intratumoral thymidylate synthase (TS) and dihydropyrimidine
      dehydrogenase (DPD) mRNA expression in colorectal and gastric cancer during
      continuous tegafur infusion.
AB  - Thymidylate synthase (TS) is the target enzyme of 5-fluorouracil (5-FU), and
      dihydropyrimidine dehydrogenase (DPD) is the key enzyme in the 5-FU catabolic
      pathway. We wanted to determine whether the TS and DPD mRNA expression levels of
      gastric and colorectal cancer patients would be affected by tegafur (futrafur:FT)
      based chemotherapy and whether changes in their expression might be responsible
      for patient outcome. Thirty-five patients with resectable advanced primary
      gastric cancer and 36 patients with resectable advanced primary colorectal cancer
      were the subjects of this study. They all underwent neoadjuvant chemotherapy with
      protracted infusion of FT alone or FT plus low doses of cisplatin. The TS and DPD
      mRNA expression levels of endoscopic biopsy specimens before chemotherapy and
      surgical specimens after chemotherapy were measured by TaqMan reverse
      transcription-PCR assay using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as
      the internal standard. There was a significant difference in the DPD mRNA levels
      during chemotherapy in the colorectal cancers. Although the TS and DPD levels
      were unrelated to any conventional histopathological grade factors, colorectal
      cancer patients whose surgical specimens contained lower TS and DPD mRNA levels
      had longer disease-free intervals. The results of this study suggest that FT may
      affect DPD mRNA expression in colorectal cancer patients, that TS/DPD expression
      can be regarded as an independent prognostic factor, and that colorectal cancer
      patients with low TS and low DPD mRNA are candidates for FT-based adjuvant
      chemotherapy. In addition, quantitative analysis of the change in TS/DPD mRNA in
      surgical specimens during FT-based chemotherapy might be a more accurate means of
      predicting the post-operative disease-free interval of colorectal cancer patients
      than analysis of endoscopic specimens before chemotherapy. There also seems to be
      a relation between regulation of TS and DPD during FT chemotherapy. Elucidation
      of the mechanisms regulating TS and DPD mRNA expression might make it possible to
      predict sensitivity and/or toxicity to FT.

PMID- 11445850
TI  - Molecular cloning and characterization of human WNT5B on chromosome 12p13.3
      region.
AB  - WNT signaling pathway plays a key role in carcinogenesis and embryogenesis. We
      have cloned and characterized the human WNT5B. Overlapping WNT5B cDNAs,
      containing 1080-bp ORF, were isolated. WNT5B encoded a 359-amino-acid polypeptide
      with the N-terminal signal peptide, four N-linked glycosylation sites, and
      consensus amino-acid residues conserved among the WNT family. WNT5B showed 80.5%
      total-amino-acid identity with WNT5A. Comparison between nucleotide sequence of
      WNT5B cDNA and human genome draft sequences revealed that the WNT5B gene,
      consisting of 4 exons, was located on human chromosome 12p13.3 region. Northern
      blot analyses with W5B2 probe detected the 2.8- and 2.4-kb WNT5B mRNAs. WNT5B was
      moderately expressed in adult prostate and fetal brain, and weakly expressed in
      fetal lung, kidney, adult liver, ovary, and small intestine. Among human cancer
      cell lines, WNT5B was expressed in gastric cancer cell lines MKN7, MKN45, KATO
      III, and a teratocarcinoma cell line NT2. WNT5B might be implicated in human
      carcinogenesis through activation of the WNT-beta-catenin-TCF signaling pathway,
      just like Wnt5a.

PMID- 11445851
TI  - Overexpression of p53 and absent genetic mutation in clear cell chondrosarcoma.
AB  - Clear cell chondrosarcoma is one of the extremely rare chondrosarcomas. The
      pathogenesis and the molecular genetic events, which contribute to the
      development of clear cell chondrosarcoma, are not well elucidated, due in part to
      the lack of sufficient tumor tissue available. To characterize the involvement of
      the p53 gene abnormality in this disease, we analyzed expression and sequence
      alteration of p53 by immunohistochemical analysis of the protein expression and
      quantitative DNA/PCR and PCR-SSCP assays of the gene in 28 paraffin-embedded
      tissue specimens. Immunohistochemical analysis demonstrated that 7 (25%) showed
      patchy positive nuclear staining for p53 and 5 (18%) showed diffuse positive
      nuclear staining patterns. Sixteen (57%) were negative for p53 immunostaining.
      Quantitative DNA/PCR analysis revealed that none of the cases we studied showed
      significantly reduced levels of p53 amplification (<0.50), strongly suggesting an
      allelic deletion of the p53 gene. In contrast, however, DNA/PCR-SSCP analysis
      failed to detect any types of mutations resulting in amino acid substitution
      within exons 5-9 regions of the gene. Taken together, our data suggest that
      genetic alteration of p53 is a relatively rare event in clear cell
      chondrosarcomas but a substantial fraction of this type of tumors carries
      abnormal overexpression of p53, which might result from an as yet unidentified
      mechanism(s).

PMID- 11445852
TI  - Adenovirally-mediated transfer of E2F-1 potentiates chemosensitivity of human
      glioma cells to temozolomide and BCNU.
AB  - The therapeutic efficacy of standard cancer treatments such as chemotherapy may
      be improved if they are combined with gene-therapy. Less than 30% of patients
      with glioblastoma multiforme respond to adjuvant chemotherapy. Actively dividing
      cells are generally more sensitive to chemotherapy than are non-dividing cells.
      To determine whether forced cell-cycle progression selectively sensitizes tumor
      cells to alkylating agents, we examined the effects of overexpressing the E2F-1
      protein (a positive regulator of cell-cycle progression) on the sensitivity of
      two malignant human glioma cell lines, U-251 MG and D-54 MG, to BCNU and
      temozolomide. Treating these cells with 20-35 microM BCNU or 20-30 microM
      temozolomide resulted in 50% growth inhibition (IC50) within 4 or 6 days,
      respectively. By contrast, cells that were first induced to overexpress E2F-1
      protein by infection with an adenoviral vector had IC50s that were 37-50% lower.
      Conversely, transferring the cyclin-dependent kinase inhibitors p16 and p21 to
      the cells, also by adenoviral infection, produced 3 to 4-fold increases in
      chemoresistance. Cell-cycle analyses showed that the combination of E2F-1
      overexpression and treatment with BCNU or temozolomide increased the proportion
      of cells in S phase, but the combination of p16 or p21 overexpression and drug
      treatment reduced the proportion of cells in S phase. These observations suggest
      that overexpression of genes that positively control cell-cycle progression may
      be useful for increasing the sensitivity of glioma cells to alkylating agents.

PMID- 11445853
TI  - Differential expression of the multidrug resistance-related protein MRP1 in the
      histological compartments of nephroblastomas.
AB  - Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some
      tumors, however, fail to respond to therapy and those patients have a poor
      prognosis. In a search for prognostic markers, we investigated the expression of
      the multidrug resistance-related protein 1 (MRP1) in 32 nephroblastomas by means
      of immunohistochemistry. The immunohistochemical results were validated with a
      real-time RT-PCR technique. MRP1 expression was heterogeneous and predominantly
      found in the blastemal and epithelial compartments compared to the stromal
      elements of nephroblastomas. We found significant relationships of MRP1
      expression to survival of patients and to expression of p53, HSP70, and LRP/MVP.
      The relationship between MRP1 and p53 expression is a clue that the
      transcriptional control of MRP1 by p53 reported for other tumor types may also
      take place in nephroblastomas. The correlation of MRP1 to other drug resistance
      genes, e.g. HSP70 and LRP/MVP in nephroblastomas indicates that the co-expression
      of different drug resistance genes may be under a common regulation of still
      unknown transcription factors.

PMID- 11445854
TI  - Apoptosis and thymidylate synthase inductions by 5-fluorouracil in gastric cancer
      cells with or without p53 mutation.
AB  - We studied apoptosis and thymidylate synthase (TS) inductions by 5-fluorouracil
      (5-FU) in gastric cancer cells with wild-type p53 (MKN-45 and MKN-74) and with
      mutated p53 (MKN-28 and KATO-III). Apoptotic inductions in MKN-45 and MKN-74 were
      stronger than those in MKN-28 and KATO-III, suggesting that wild-type p53 may
      contribute to the induction of apoptosis. After continuous exposure to 0.1
      microg/ml of 5-FU for 96 h, no TS induction was obtained in KATO-III, while
      approximately twice the amount of TS was observed compared to non-treatment cells
      in MKN-45, MKN-74, and MKN-28. The results of immunohistochemical staining for TS
      and p53 showed no relation between these two protein expressions in endoscopic
      biopsy specimens of 25 patients with advanced gastric cancer. These results
      indicated that p53 status may not play a pivotal role in regulating TS
      expression. We found no significantly different effects of 5-FU between
      intermittent (repeat of 24-h continuous infusion and 24-h drug-free) and
      continuous treatments in either MKN-28 or stem cells (CD34+ hematopoietic
      progenitor cells) when the same area under the time-concentration curve of 5-FU
      was administered. The TS induction in MKN-28 cells by intermittent treatment was
      significantly higher than that by continuous treatment; however, most TSs in both
      types of 5-FU treatment cells were of the inactive form, i.e., TS bound to FdUMP,
      a 5-FU metabolite. Therefore, neither intermittent nor continuous treatment
      appears to induce 5-FU resistance related to the level of increment free TS. In
      conclusion, our observations suggested that p53 mutation may be associated with
      apoptotic induction by 5-FU; however, p53 status may not strongly affect TS
      induction by 5-FU. Intermittent treatment can be replaced with continuous
      treatment without causing 5-FU resistance.

PMID- 11445855
TI  - The skeletal metastatic complications of renal cell carcinoma.
AB  - Of the 103 patients with advanced renal cell carcinoma 31 (30%) developed
      symptomatic radiologically confirmed skeletal metastases. These were typically
      lytic, predominantly affecting the axial skeleton and associated with
      considerable skeletal morbidity. Solitary bone lesions occurred in 14 (45%) of
      patients. The median survival of patients with bone metastases was 12 months.
      Hypercalcaemia was common in patients both with (29%) and without (44%) bone
      metastases. The number and rate of skeletal related events was similar to that
      seen from bone metastases from breast cancer. It would therefore be appropriate
      to evaluate the effectiveness of bisphosphonate treatment for reducing skeletal
      morbidity in advanced renal cell cancer with bone metastases.

PMID- 11445856
TI  - Polymorphism in the thymidylate synthase promoter enhancer region in colorectal
      cancer.
AB  - Thymidylate synthase (TS) is an important target for chemotherapy drugs such as 5
      fluorouracil and raltitrexed. Over-expression of TS has been linked to
      chemotherapy resistance. A polymorphic tandem repeat sequence in the 5'
      untranslated region (5'UTR) of the human TS gene (TSER) has been shown to
      influence TS expression. The presence of a triple tandem repeat (TSER*3)
      increases in vitro TS expression compared to a double tandem repeat (TSER*2) and
      is associated with higher in vivo tumor TS activity. The polymorphism of this
      promoter enhancer region has not been extensively studied in patients with cancer
      and may represent a possible mechanism of intrinsic resistance to TS inhibitors.
      In this study, PCR analysis of genomic DNA from 121 patients with colorectal
      cancer demonstrated 29% of patients were homozygous for TSER*3, 16% were
      homozygous for TSER*2 and 55% were heterozygous. In 44/45 microdissected tumors
      the TS enhancer genotype was identical between paired samples of colorectal tumor
      and normal tissue. In 24 patients receiving a bolus/infusion 5-fluorouracil (5FU)
      regimen for metastatic colorectal cancer, 22% of non-responders to chemotherapy
      were homozygous for TSER*2 compared with 40% of responders. Median survival
      dropped from 16 months for homozygous TSER*2 to 12 months for homozygous TSER*3.
      This is consistent with previous studies where higher TS expression was
      associated with poor response to TS inhibitors. Prospective analysis of the
      influence of the TS polymorphism on patient outcome is warranted.

PMID- 11445857
TI  - Clonal heterogeneity of p53 mutations in ovarian cancer.
AB  - We analyzed clonal populations of ovarian cancer cells for heterogeneity in p53
      mutations (exons 4-9) and chemosensitivity. UL-3A cells were developed from a
      patient with stage IIIC ovarian adenocarcinoma. Heterogeneity in p53 mutations
      was demonstrated, ranging from point mutations to deletions in exons 4, 6 and 7.
      UL-3A cells contained two point mutations, in codon 248 of exon 7 and in codon 76
      of exon 4. Five groups of clones were identified according to the p53 mutations.
      UL-3A clones with low p53 levels were more sensitive to CDDP (LD50 <8.0
      microg/ml). Heterogeneity of p53 mutations may provide growth advantage during
      disease progression or chemotherapy.

PMID- 11445858
TI  - Involvement of PI3K in PKCepsilon-mediated oncogenic signal in rat colonic
      epithelial cells.
AB  - We have recently demonstrated that overexpression of PKCepsilon is oncogenic in
      colonic epithelial cells. To test whether PI3K might be an upstream effector of
      PKCepsilon in cell transformation, we have overexpressed the p110alpha PI3K
      subunit in non-transformed D/WT colonic epithelial cells. Transfectants displayed
      the major in vitro features of transformed cells. Interestingly, no
      transformation occurred when p110alpha was co-transfected with a dead-kinase
      PKCepsilon mutant. The p85alpha subunit of PI3K, displaying a dominant-negative
      like effect, was then transfected in PKCepsilon-transformed D/epsilon cells. The
      transformed profile of these cells was markedly reduced. To identify which by
      products of PI3K might be involved in cell transformation we have transfected the
      D/WT cell line with cDNAs encoding the PI3 kinases hVps34 and C2beta.
      Overexpression of hVps34 did not cause cell transformation. Conversely, in vitro
      transformation was observed when C2beta was transfected into D/WT cells. These
      results indicate that phosphatidylinositol-3 monophosphate does not seem to be
      involved in cell transformation, and that phosphatidylinositol-3,4 bisphosphate
      and phosphatidylinositol-3,4,5 trisphosphate are more likely involved in this
      process. Thus, our data support the hypothesis of a linkage between PI3K and
      PKCepsilon, and indicate that PI3K may act as a source of second messengers
      responsible for oncogenic activation of PKCepsilon.

PMID- 11445859
TI  - Microsatellite and chromosome instability in squamous cell laryngeal carcinoma.
AB  - Head-and neck squamous cell carcinoma (HNSCC) represents almost 5% of all
      malignancies in Europe. The aetiology of HNSCC is complex, with both genetic and
      mutagenic factors involved. The aim of the present study was to investigate the
      loss of heterozygosity (LOH), mainly at tumour suppressor loci (using markers
      D1S2883, D2S123, D3S1611, D5S346, D7S501, D8S254, TP53, NM23), microsatellite
      instability (BAT25, 26, 40) and <hidden chromosome instability> (bleomycin test)
      in patients with squamous cell larynx cancer. In a group of 20 patients LOH was
      observed mainly at the loci 3p (64.7%), 8q (71.4%), 17q (M1-30.8%, M2-25%, M3
      38.5%). Despite chromosomal instability detected by bleomycin no microsatellite
      instability was observed.

PMID- 11445860
TI  - Soluble low-molecular-mass tumor-associated proteins promote the suppression of
      mammary tumors by cyclophosphamide.
AB  - This study examined whether the soluble tumor-associated-antigens (TAA), of 66
      kDa and 51 kDa, could promote suppression by anticancer drugs of chemically
      induced mammary tumorigenesis. Dimethylbenzanthracene (DMBA, 10 mg/rat, twice)
      was used to induce mammary tumors. Then, for nine more weeks, the preparation of
      TAA and cyclophosphamide (CPA), alone or in combination with TAA, were
      administered in weekly doses. Twenty weeks after DMBA exposure, the mammary tumor
      yield was 2.4, 2.8 and 2.9 in the experimental groups compared to 3.5 in the
      controls. Seventy-five percent of the rats in the control group, but only 37% of
      TAA, 50% of the CPA, and 30% of the CPA and TAA treated animals had malignant
      tumors. In the experimental groups, 6.5%, 25% and 38%, respectively, of the
      tumors regressed, compared to 3% in controls. In the groups receiving CPA or TAA,
      regression was observed in the fifth week of treatment, and in the group
      receiving combined treatment, already in the first week. The size of the tumors
      in control rats increased during the last 10 weeks 3.6 times, in the CPA treated
      rats 1.15 times, but in those receiving CPA plus TAA it decreased by 0.7 times.
      The results of our experiment demonstrated that TAA have distinct tumor
      suppressive properties, and can enhance the anticancer effects of CPA.

PMID- 11445861
TI  - Health status and health-related quality of life in survivors of cancer in
      childhood in Latin America: a MISPHO feasibility study.
AB  - Cancer is an increasing cause of disease-related death in childhood within
      developing countries, where the great majority of the world's children reside.
      The improving prospects for survival in such children, and the corresponding
      challenge of undertaking economic evaluations of related health interventions,
      provide a stimulus to study the health-status and health-related quality of life
      in survivors of cancer in childhood in Latin America. Spanish language versions
      of questionnaires for proxy assessors, based on the Health Utilities Index (HUI),
      were used to elicit responses from parents and physicians. The HUI is a family of
      multi-attribute, generic, preference-linked measures of health status and health
      related quality of life that are reliable, responsive and valid, and have been
      used previously in pediatric oncology. Valid responses were received from 178
      parents and 144 physicians in 6 centres in 4 countries (Cuba, Honduras, Colombia
      and Uruguay). For children with acute lymphoblastic leukemia the major morbidity
      burdens were in the attributes of emotion, cognition and pain. The overall burden
      of morbidity was greater in children with non-Hodgkin's lymphoma. In survivors of
      Hodgkin's disease and Wilms' tumor the attributes most affected were emotion and
      pain. In general, there was considerable agreement between the assessments
      provided independently by parents and physicians. This study demonstrates the
      feasibility of conducting such measurements in developing countries, and reveals
      similarities in health status and health-related quality of life to comparable
      populations in more privileged societies.

PMID- 11445862
TI  - The small GTPase Rac interacts with ubiquitination complex proteins Cullin-1 and
      CDC23.
AB  - Racs are involved in the regulation of important cellular processes including
      mitogenesis. We found that the E3 ubiquitination ligase subunit Cullin-1
      interacts with constitutively active Rac3 but not with wild-type Rac3 in yeast.
      In mammalian cell lysates, Cullin-1 bound to V12Rac3, effector domain mutants
      V12L37Rac3 and V12H40Rac3, and insert domain deletion mutant V12Rac3DeltaIns(124
      135). Cullin-1 also formed a clearly detectable complex with other activated Rac3
      related proteins including Rac1, Rac2, Cdc42 and RhoA but not with the distantly
      related small GTPase Rap1. Since the proteasome is involved in cell cycle control
      through the programmed degradation of cell cycle proteins, the possible
      regulation of Rac levels during the cell cycle was examined. However, Rac was
      expressed at constant levels throughout the cell cycle, and a specific proteasome
      inhibitor had no effect on Rac protein levels. These combined results indicate
      that the binding of activated Rac to Cullin-1 does not affect Rac protein levels,
      nor does it mediate the regulation of mitogenesis by Rac. However, Rac-Cullin-1
      interactions may serve to regulate other E3 ligase functions such as subcellular
      localization. Indeed, activated Rac3 and Cullin-1 co-localized to the perinuclear
      region of the cell. We also detected complex formation between Rac and the APC
      component CDC23. These results indicate that Rac may regulate specific
      proteolytic processes through directed subcellular localization of SCF or APC
      complexes.

PMID- 11445863
TI  - CD71 antibody enhances iron uptake by mouse bone marrow cells and the survival
      potential of erythroid progenitor cells.
AB  - Transferrin has been shown to have cytoprotective functions. The aim of this
      study was to evaluate the effect of antibody against CD71 (transferrin receptor)
      on survival potential of erythroid progenitor cells. After anti-CD71 IgG or
      control IgG was reacted with cells for 20 min on ice, the uptake of transferrin
      bound 59Fe by the MEL cells or the mouse bone marrow cells during 2-day
      incubation without erythropoietin was measured. Erythropoiesis was evaluated by
      addition of erythropoietin after 4-5 weeks' culture without erythropoietin or
      beta-mercaptoethanol, and production of cells containing hemoglobin was compared
      by immunocytological methods. MEL cells reacted with anti-CD71 IgG incorporated
      more transferrin-bound 59Fe than MEL cells reacted with control IgG. Uptake of
      transferrin-bound 59Fe by mouse bone marrow cells reacted with anti-CD71 IgG was
      also greater than by cells reacted with control IgG. Erythrocytes developed from
      cells reacted with anti-CD71 IgG and cultured for 4-5 weeks, but few erythrocytes
      developed from cells reacted with control IgG. Bone marrow cells depleted of
      TER119+ cells, CD34+ cells, or CD45+ cells and reacted with CD71 antibody did not
      differentiate into erythrocytes. Survival potential of erythroid progenitor cells
      were enhanced by reaction with anti-CD71 antibody.

PMID- 11445864
TI  - Expression of angiogenic factors and apoptotic factors in leiomyosarcoma and
      leiomyoma.
AB  - Angiogenesis is essential for tumor growth and metastasis. Some angiogenic
      factors, such as vascular endothelial growth factor (VEGF), platelet-derived
      endothelial cell growth factor (PD-ECGF), transforming growth factor-alpha (TGF
      alpha) and basic fibroblast growth factor (bFGF) are involved in increased
      angiogenic activity and disease progression in many carcinomas. However, there is
      little information regarding the association between angiogenic factors and
      leiomyosarcoma. Although there are abundant vessels in the sarcoma which enable
      it to easily receive nutrition and medicinal components, chemotherapy cannot
      effectively treat leiomyosarcoma. This means the resistance to anticancer drugs
      in leiomyosarcoma is very strong. However, the resistant mechanism is still
      unclear. In this study, expressions of VEGF, PD-ECGF, TGF-alpha, bFGF,
      intratumoral microvessel density (IMVD), and p53, Bcl-2 and Bax were examined by
      immunohistochemistry in 30 patients with leiomyosarcoma and 21 patients with
      leiomyoma. With regard to angiogenesis, PD-ECGF and TGF-alpha were closely
      associated with an increase in IMVD (p=0.012, 0.0196, respectively), and VEGF and
      PD-ECGF were significantly expressed in leiomyosarcoma compared with leiomyoma
      (p=0.041, 0.041, respectively). Although p53 expression in leiomyosarcoma was
      significantly higher than in leiomyoma (p=0.016), the frequency of p53 positivity
      was not so high (47%). On the other hand, the ratio of Bcl-2/Bax in
      leiomyosarcoma was significantly higher than that in leiomyoma (p=0.033). The
      findings of this study suggest that in leiomyosarcoma, angiogenic factors, such
      as PD-ECGF, VEGF and TGF-alpha expression may be involved in tumor angiogenesis,
      and the frequently high ratio of Bcl-2/Bax and expression of p53 gene mutation
      might be related to chemoresistance mechanism.

PMID- 11445865
TI  - Invasive properties of serous human epithelial ovarian tumors are related to Ets
      1, MMP-1 and MMP-9 expression.
AB  - The invasive potential of serous epithelial ovarian tumors is the main factor
      determining their biological behaviour. In contrast to invasive serous ovarian
      carcinomas serous borderline tumors generally present without stromal invasion
      and without or non-invading peritoneal implants. Little is known about the
      reasons underlying these differences. In the present study we found that two
      matrix-degrading metalloproteinases, collagenases 1 and 4 (MMPs 1 and 9), as well
      as the Ets-1 transcription factor are expressed at very low levels in serous
      benign cystadenomas, upregulated in the fibroblastic stroma, but not in the
      epithelium of borderline tumors and most strongly expressed in both stromal and
      epithelial tumor cells of serous invasive carcinomas. Since expression of Ets-1
      and of MMPs 1 and 9 are topographically related, a transcriptional regulation of
      both proteases by Ets-1 is suggested. Upregulation of MMPs 1 and 9 within
      fibroblastic stromal cells of borderline tumors might be related to matrix
      remodelling and additional expression of both enzymes by the neoplastic cells of
      invasive carcinomas could then allow invasive propagation. The different
      expression patterns might supports the view, that no transition of serous
      borderline tumors into invasive carcinomas occurs.

PMID- 11445866
TI  - Uptake of tritiated D-mannoheptulose by liver, pancreatic exocrine and endocrine
      cells.
AB  - Tritiated D-mannoheptulose, a ketoheptose known to inhibit D-glucose metabolism
      in hepatocytes and pancreatic islets, but not so in pancreatic acinar cells, was
      injected intravenously in streptozotocin-induced diabetic mice transplanted under
      the kidney capsule with islets from control mice of the same strain. One hour
      after the injection of the tritiated heptose, the radioactive content was 5-8
      times higher in the liver and transplanted islets than in the pancreatic gland.
      It is proposed that suitably radiolabelled D-mannoheptulose could be used to
      label preferentially the endocrine moiety of the pancreatic gland, e.g., in the
      perspective of its non-invasive imaging.

PMID- 11445867
TI  - Proliferating cell nuclear antigen labeling index and p53 expression predict
      outcome for breast cancer patients with four or more lymph node metastases.
AB  - In general, extensive lymph node metastasis indicates poor prognosis in breast
      cancer. Nevertheless, some patients with this condition survive for a long time
      without recurrent disease. This study involved 112 breast cancer patients with
      four or more lymph node metastases and without distant metastasis who underwent
      surgery. p53 expression was associated with shorter overall and disease-free
      survival. High PCNA labeling index was associated with shorter overall disease
      free survival. p53-negative and low-PCNA patients survived much longer than p53
      positive and high-PCNA patients. This study showed that p53-negative or low-PCNA
      index patients have relatively good prognoses despite extensive lymph node
      metastasis.

PMID- 11445868
TI  - HIV gp120 and morphine alter mu opiate receptor expression in human vascular
      endothelium.
AB  - We find that chronic exposure of human saphenous vein, atria and internal
      thoracic artery endothelium to the human immunodeficiency virus surface
      glycoprotein gp120, results in an increase in endothelial mu opioid receptor
      expression (52%). gp120 acts, in this regard, as a proinflammatory cytokine (e.g.
      interleukin-1-alpha) by increasing endothelial mu opioid receptor expression. In
      contrast, morphine decreases mu opioid receptor expression by 90% in a dose
      dependent fashion. Pretreatment of these tissues with the respective antagonists
      e.g., naloxone and anti-gp120 blocks the opiate decrease and increase gp120
      induced increase in mu expression, respectively. Further, pretreatment of these
      endothelia with morphine inhibits gp120-stimulated mu transcript expression.
      Therefore, the immune down-regulating action of morphine may prevent viral
      replication because this process requires immune activation that can, in part, be
      provided for by gp120 proinflammatory actions.

PMID- 11445869
TI  - Clinical phenotype of triplicated alpha-globin genes and heterozygosity for beta0
      thalassemia in Chinese subjects.
AB  - The presence of extra copies of alpha-globin gene has been shown to worsen the
      degree of anemia in beta-thalassemia heterozygotes. We describe the clinical
      phenotype of eight Chinese subjects with heterozygosity for both triplicated
      alpha-globin gene and a beta0-thalassemia allele. They were identified through
      genotyping of beta-thalassemia intermedia and major patients, and through
      community-based thalassemia screening program in Hong Kong. Standard molecular
      techniques were used in the determination of genotype. All subjects in this
      series showed five copies of alpha-globin genes (alphaalphaalpha/alphaalpha) in
      association with a beta0-thalassemia allele. Although genotypically identical,
      six subjects showed a beta-thalassemia intermedia phenotype while two were
      clinically indistinguishable from beta-thalassemia minor, implying the presence
      of genetic modifying factors that remained undefined. Triplication of alpha
      globin gene and heterozygosity for beta0-thalassemia accounted for 15% of beta
      thalassemia intermedia patients at our locality and was associated with a mild
      clinical phenotype. This genotype was not found among beta-thalassemia major
      patients. They presented in adulthood and were usually not transfusion dependent.
      When compared with simple beta-thalassemia heterozygotes, they showed obvious red
      cell abnormalities (hypochromasia, anisopoikilocytosis, circulating normoblasts),
      lower hemoglobin (Hb) and higher HbF levels. The presence of triplicated alpha
      globin genes should always be considered in apparent beta-thalassemia carriers
      who were more symptomatic than expected, so that unnecessary investigations for
      the cause of anemia could be avoided. Finally, triplication of alpha-globin genes
      should be looked for in families with children affected by beta-thalassemia
      intermedia in which only one parent showed a picture of beta-thalassemia on Hb
      analysis.

PMID- 11445870
TI  - Assessment by D-[(3)H]mannoheptulose uptake of B-cell density in isolated
      pancreatic islets from Goto-Kakizaki rats.
AB  - The uptake of D-[3H]mannoheptulose by isolated pancreatic islets was recently
      proposed as a tool to assess the relative contribution of insulin-producing cells
      to the total mass of the islets. In the present study, the uptake of the
      tritiated heptose over 60 min incubation at 37 degrees C was about 21% lower in
      islets from hereditarily diabetic rats (GK rats) than in islets from control
      animals, this decrease being virtually identical to that documented previously by
      morphometric analysis of islets from the same type of rats. The intracellular
      3HOH space and extracellular [U-14C]sucrose space were not significantly
      different in control and diabetic rats, at least when the comparison was
      restricted to animals of the same sex. There was a trend, however, towards a
      somewhat lower D-[5-3H]-glucose intracellular distribution space in islets from
      GK rats, as compared to control animals. These findings provide further support
      to the validity of D-[3H]mannoheptulose uptake as a tool to assess the density of
      insulin-producing cells in isolated islets.

PMID- 11445871
TI  - NC-1500 prevents concanavalin A-induced mice hepatitis without affecting cytokine
      gene expression.
AB  - NC-1500 is a dihydropyridine type calcium channel blocker. The effect of NC-1500
      on mice concanavalin A-induced hepatitis was examined. Treatment of mice with
      concanavalin A (Con A) caused elevation of plasma transaminase. Pretreatment of
      mice with NC-1500 (3, 10 and 30 mg/kg, p.o.) prevented this Con A-induced
      elevation of plasma transaminase. Treatment of mice with Con A induced tumor
      necrosis factor-alpha (TNF-alpha) mRNA expression in the liver. However, NC-1500
      (30 mg/kg, p.o.) did not affect this Con A-induced TNF-alpha mRNA expression in
      the liver. The present results showed that NC-1500 inhibited Con A-induced
      hepatitis without affecting TNF-alpha mRNA expression in the liver.

PMID- 11445872
TI  - Statistical pattern analysis of gene expression profiles for glioblastoma tissues
      and cell lines.
AB  - The recent development and refinement of cDNA array and genechip techniques
      allows for large-scale parallel screening of gene expression and thereby provides
      a global assessment of molecular events transpiring in cell populations. We
      hypothesized that such an approach might help illuminate current issues in glioma
      research. To what degree are glioblastoma multiforme (GBM) cell lines
      representative of primary GBM tumors? We carried out a gene expression profiling
      study using cDNA array technology on 10 GBM primary tissues and 3 GBM cell lines.
      The gene expression levels were quantified, and the within-subject ranks of the
      gene expression levels were subsequently evaluated by hierarchical clustering
      analysis, multidimensional scaling analysis, and principal component analysis.
      Hierarchical cluster analysis shows that the 3 cell lines form one main cluster
      and the 10 tissue samples form a separate cluster. Multidimensional scaling and
      principal components analysis provided further graphical demonstration that the
      cell lines are clearly different from the tissue samples and that the cell lines
      are more different between themselves than are the tissues.

PMID- 11445873
TI  - Frequency of the recessive 30delG mutation in the GJB2 gene in Northeast
      Hungarian individuals and patients with hearing impairment.
AB  - Mutations in the GJB2 gene, which encodes a gap junction protein (connexin 26)
      account for up to 50% of cases of congenital autosomal recessive non-syndromic
      hearing impairment. A single mutation, 30delG, is responsible for 70% of this
      autosomal recessive hearing loss in Europe. This study describes the 30delG
      mutation analysis of 23 Hungarian families (64 individuals) with at least two
      subjects with congenital non-syndromic hearing defect and of 52 unrelated
      individuals from the Northeastern population of Hungary. In all patients, non
      progressive hearing impairment varied from moderate to profound involving all
      frequencies. DNA was tested by PCR based restriction enzyme assay (BSiYI). Sixty
      four percent of the patients displayed this one base deletion in GJB2. Out of
      these, 65.9% were homozygous for this mutation and 34.1% were heterozygotes. The
      latter showed compound heterozygosity since in these 14 patients, eight
      previously reported different nucleotide changes were observed on the second
      allele. The carrier frequency of the 30delG mutation among control group was one
      in 10.4 (9.6%). This high frequency of 30delG corresponds more to frequencies
      reported in Southern than in North Europeans.

PMID- 11445874
TI  - Detection of amplified int-2/FGF-3 gene in primary breast carcinomas using
      differential polymerase chain reaction.
AB  - Amplification of int-2/FGF-3 gene was investigated by differential polymerase
      chain reaction (dPCR) in 440 archival primary breast carcinoma tissues. Of these,
      23 were comedo ductal carcinoma in situ (DCIS), 18 were non-comedo DCIS, 41 were
      comedo DCIS with adjacent invasive ductal carcinomas, 19 were non-comedo DCIS
      with adjacent invasive ductal carcinomas, 270 were invasive ductal carcinomas, 33
      were invasive lobular carcinomas, 21 were colloid carcinomas and 15 were
      medullary carcinomas. Int-2 was amplified in 22% (96/440) of the primary breast
      carcinomas. It was shown that int-2 was amplified in 13% (3/23) of the comedo
      DCIS, 17% (7/41) of the comedo DCIS and 29% (12/41) of the adjacent invasive
      ductal carcinomas, 26% (71/270) of the invasive ductal carcinomas, 18% (6/33) of
      the invasive lobular carcinomas, 10% (2/21) of the colloid carcinomas and 13%
      (2/15) of the medullary carcinomas. In contrast, int-2 was not amplified in non
      comedo DCIS and invasive ductal carcinomas with adjacent non-comedo DCIS lesions.
      A significant association was observed between int-2 amplification in the in situ
      components and adjacent invasive lesion (P<0.05). All tumors with int-2
      amplification in the in situ lesions (7/7) also demonstrated same degree of
      amplification in the adjacent invasive components. However, 9% (5/53) of the
      tumors with no amplified int-2 gene in the in situ components showed int-2
      amplification in the adjacent invasive lesions. A significant relationship was
      noted between amplification of int-2 and lymph node metastases (P<0.05) and
      poorly differentiated tumors (P<0.05) but not with estrogen receptor status
      (P>0.05) and proliferation index (Ki-67 and PCNA) (P>0.05). In Malaysia, majority
      of the patients belong to younger age group (<50 years old) but a comparison of
      the age groups showed that the amplification of int-2 was not statistically
      associated with patient age (P>0.05). These observations indicate that
      amplification of int-2 tends to strengthen the view that int-2 may have the
      potential to be an indicator of poor prognosis regardless of the age of the
      patient. Moreover, the presence of int-2 amplification in preinvasive,
      preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that
      int-2 could be a marker of genetic instability occurring in early and late stages
      of tumor development.

PMID- 11445875
TI  - Locomotion of lymphocytes towards melanoma cells treated with tumor necrosis
      factor in a syngeneic in vitro model.
AB  - Tumor necrosis factor (TNF) causes cell necrosis in vivo by damaging the
      endothelium of the neovasculature. However, its mechanism of action is not well
      understood. We hypothesized that TNF affects the tumor microenvironment even
      before neovascularization occurs, thereby increasing lymphocyte locomotion
      through the peritumoral matrix, a crucial step in tumor cell killing. The effect
      of TNF on lymphocytes was tested with the type I rat-tail collagen mini-assay in
      peripheral blood lymphocytes (PBL) from normal donors, a non-migratory PBL cell
      line (HPB), and a C3H mice splenic lymphocytes. Melanoma cell line (k1735p) was
      treated with TNFalpha/TNFbeta 10 or 20 pg/microl. The syngeneic splenic
      lymphocytes were layered on top of the collagen, and their migration into the
      collagen towards the tumor cells was assessed. Tumor cell viability was evaluated
      before and after TNF treatment. Paired two-tailed Student's t-test was used for
      statistical analysis. TNFalpha and TNFbeta had no significant direct effect on
      locomotion of PBL or HPB. Lymphocyte locomotion was inhibited in the presence of
      untreated melanoma cells in 7 of 9 assays (statistically significant in four),
      and it was significantly increased towards TNFalpha- or beta-treated melanoma
      cells, compared to untreated condition, in 7 of 9 assays (p=0.05 to p=0.0001).
      The number of viable tumor cells was not significantly different before and after
      treatment. In conclusion, treatment of tumor cells with TNFalpha or TNFbeta
      significantly enhances lymphocyte locomotion through the matrix. The effect of
      TNF is not the result of a direct influence on the lymphocytes, and is not
      associated with a decrease in the number of viable tumor cells. These findings
      suggest that TNF interaction with the cell microenvironment induces a change in
      lymphocyte locomotion.

PMID- 11445876
TI  - Identification of SNPs in human gamma aminobutyric acid A receptor gamma2 gene.
AB  - Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter. Because of
      its importance and diverse functions, studies of single nucleotide polymorphisms
      in the GABA receptor genes are of great significance, which may produce useful
      molecular markers for genetic analysis of neurological disease, and possibly lead
      to the discovery of pathogenic mutations. We identified eleven SNPs in the entire
      exon regions, immediate intron regions and promoter region of human GABA receptor
      gamma2 gene by direct sequencing. In this discovery, 2 non-synonymous cSNPs and 1
      splicing variant are found.

PMID- 11445877
TI  - Alteration of A549 carcinoma cell protein synthesis profile induced by lung
      cancer patient serum.
AB  - Several elements such as circulating DNA and metastatic cells, containing the
      same primary tumor mutations, oncogenic proteins, cytokines, and other tumor
      related not yet identified factors, can be found in the blood stream of cancer
      patients. In this study we have shown that serum factors presented in lung cancer
      patients can modify the protein profile of the lung adenocarcinoma cell line
      (A549). This alteration in cellular protein profile can be an important event in
      the cell phenotype modification necessary for the advance of the disease. There
      have been no similar studies regarding cancer cell protein synthesis induction by
      human cancer serum.

PMID- 11445878
TI  - Introduction: European bioethics on a rocky road.
AB  - There are quite a number of rocky roads on which the 'old continent' has
      embarked. There is, first, a harmonization of cultures and attitudes in the
      creation of a common European market of values and valuables, a harmonization
      undertaken in order to survive in an increasingly competitive global market.
      Second, there is a reactivation of specific European traditions in discourse,
      peaceable hermeneutics, solidarity, subsidiarity, tolerance in both conflict
      reduction and solution, and respect for self-determination and self
      responsibility. Third, there is an integration of theory and practice, of visions
      and reality, of national identity or pride and common European rights, and of
      obligations and cultural heritages. Last but not least, there is a question about
      the definition of 'European' in a world which, at least in part, has been
      developed by successful European missionary work in the distribution of Age-of
      Reason principles such as personal autonomy and social and ideational tolerance,
      the promotion of science-based technologies, and the creation of global markets
      for goods and services.

PMID- 11445879
TI  - Regulating moral dissent in an open society: The Dutch experience with pragmatic
      tolerance.
AB  - In pluralistic modern societies, moral dissent will, to an increasing extent, be
      an inescapable fact in our lives. Moral dissent, however, involves various
      serious dangers: escalation of conflicts, the use of violence, flourishing of
      radical extremism and even civil war. There are basically two ways in which these
      threats can be addressed: coercive enforcement of consensus or tolerance. First,
      we could try to eliminate moral dissent by using more dictatorial forms of
      consensus formation, like propaganda, indoctrination and terror. This, however,
      would endanger or even destroy the open society. Therefore, from a moral point of
      view, tolerance appears to be the more desirable antidote to the unwanted effects
      of moral dissent. This paper aims to contribute to the discussions about the
      regulation of moral dissent and the formation of moral consensus by analyzing one
      of the most important and idiosyncratic elements of the Dutch way of handling
      these issues: pragmatic tolerance. First, some general thoughts are developed
      about moral consensus, moral dissent and tolerance as a means of regulating
      dissent. In addition, the characteristic Dutch policy of pragmatic tolerance is
      described. Finally, some of the pros and cons of pragmatic tolerance are analyzed
      from an ethical perspective.

PMID- 11445880
TI  - Interactive technology assessment and wide reflective equilibrium.
AB  - Interactive technology assessment (iTA) provides an answer to the ethical problem
      of normative bias in evaluation research. This normative bias develops when
      relevant perspectives on the evaluand (the thing being evaluated) are neglected.
      In iTA this bias is overcome by incorporating different perspectives into the
      assessment. As a consequence, justification of decisions based on the assessment
      is provided by stakeholders having achieved agreement. In this article, agreement
      is identified with wide reflective equilibrium to show that it indeed has the
      potential of justifying decisions. We work out several conditions for this
      agreement to be achievable and just.

PMID- 11445881
TI  - Euroscreen 2: towards community policy on insurance, commercialization and public
      awareness.
AB  - The project Euroscreen 2 has examined genetic screening and testing with
      particular reference to implications for insurance, commercialization through
      marketing of genetic tests direct to the public, and issues surrounding raising
      public awareness of these and other developments in genetics, including the
      practical experiment of a Gene Shop. This paper provides a snapshot of the three
      year project. The study group's work included monitoring developments in
      different European countries and exploring possibilities for regulation in
      insurance and commercialization together with public attitudes to regulation. The
      success or failure of different strategies is not independent of public
      awareness. Exploration of policy, however, also requires examination of
      fundamental concepts such as solidarity and geneticization.

PMID- 11445882
TI  - Commercialization, patents and moral assessment of biotechnology products.
AB  - The biotechnology patent debates have revealed deep moral concerns about basic
      genetics research, R&D and specific biotechnological products, concerns that are
      seldom taken into consideration in Technology Assessment. In this paper important
      moral concerns are examined which appear at the various stages of development of
      a specific genetic product: a predictive genetic test. The purpose is to
      illustrate the need for a more contextual approach in technology assessment,
      which integrates the various forms of interaction between bio-technology and
      society or societal segments. Such an approach will generate greater insight in
      the moral issues at all stages of a product's life-cycle and this will facilitate
      decision-making on the 'morality' of a specific biotechnological product.

PMID- 11445883
TI  - Acculturating human experimentation: an empirical survey in France.
AB  - Preliminary results of an empirical study of human experimentation practices are
      presented and contrasted with those of a survey conducted a hundred years ago
      when clinical research, although tolerated, was culturally deviant. Now that
      biomedical research is both authorized and controlled, its actors (sponsors,
      committees, investigators, subjects) come out with heterogeneous rationalities,
      and they appear to be engaged in a transactional process of negotiating their
      rationales with one another. In the European context "protective" of subjects,
      surprisingly the subjects we interviewed (and especially patient-subjects) were
      creative and revealed an aptitude for integrating experimental medicine into
      common culture.

PMID- 11445884
TI  - New developments in Dutch legislation concerning euthanasia and physician
      assisted suicide.
AB  - Dutch euthanasia and physician-assisted suicide stand on the eve of important
      legal changes. In the summer of 1999, a new government bill concerning euthanasia
      and physician-assisted suicide was sent to Parliament for discussion. This bill
      legally embodies a ground for exemption from punishment for physicians who
      conduct euthanasia or physician-assisted suicide and comply with certain
      requirements. On November 28, 2000, the Dutch parliament approved an adapted
      version of this bill. Since the approval by the Dutch Senate can be regarded as a
      formality, it is expected that the bill will come into force in the course of
      this year (2001). In this paper we discuss these new developments.

PMID- 11445885
TI  - Abortion without free and informed consent? An Austrian case of first impression.
AB  - Notwithstanding the question of whether abortion is generally or exceptionally a
      legitimate means of family planning, it is basically agreed that abortion is not
      justifiable without free and informed consent of the pregnant woman. However, if
      abortion is held by the legislature to be a "ground of justification" (i.e., a
      far-reaching exception to criminal liability), is it true that abortion may also
      be carried out for the benefit of a pregnant woman who is not able to give free
      and informed consent? Should a substituted-judgment approach be applied in cases
      where the woman is incompetent to decide? Or should the pregnant woman's
      relatives' interests be taken into account exclusively? The author tries to
      answer these questions, which were tackled by the Austrian Supreme Court in a
      recent case.

PMID- 11445886
TI  - Perils and deficiencies of the European Convention on Human Rights and
      Biomedicine.
AB  - The authors analyze deficiencies and perils of the European Convention on Human
      Rights and Biomedicine, in particular the concept of human rights as given by
      natural law and the Convention's stand on germline therapy and its refutation of
      therapeutic enhancement.

PMID- 11445887
TI  - Ozone exposure and the production of reactive oxygen species by bronchoalveolar
      cells in humans.
AB  - Exposure to ozone injures respiratory epithelium, and the mechanisms may involve
      the generation of reactive oxygen species (ROS). This study tested the hypothesis
      that ozone exposure increases the airway burden of ROS to a greater degree in
      smokers than nonsmokers, and that this effect is independent of ozone-induced
      changes in spirometry. Healthy subjects were selected as either responders
      (decrement in FEV1 > 15%) or nonresponders (decrement in FEV1 < 5%) to ozone;
      each underwent 2 exposures to ozone and 1 to air, with bronchoalveolar lavage
      (BAL) performed 30 min (early) and 18 h (late) after exposure. Release of
      superoxide anion (O2(-)) was used as a measure of ROS release by all BAL cells,
      and flow cytometry was used to detect ROS production in alveolar macrophages (AM)
      only. Recovery of AM was approximately threefold greater in smokers than
      nonsmokers. Unstimulated, but not stimulated, cells obtained by BAL from smokers
      released approximately twofold greater amounts of O2(-) than cells from
      nonsmokers, both early and late after ozone exposure (p =.012 and p =.046,
      respectively). Stimulated, but not unstimulated, ROS generation by AM from
      smokers increased following ozone exposure, but the ozone effect was not
      significant. ROS production by AM decreased in nonsmokers (air vs. ozone late, p
      =.014). Total protein, albumin, and immunoglobulin M (IgM) increased in BAL
      fluid, consistent with an increase in epithelial permeability. In addition, the
      concentration of alpha2-macroglobulin increased approximately threefold 18 h
      after exposure in nonsmokers (p <.001). No relationship was found between
      measures of ROS production and lung function responsiveness to ozone. These
      studies suggest the airways of smokers experience a greater burden of ROS than
      those of nonsmokers following ozone exposure.

PMID- 11445888
TI  - Neutrophils in lung inflammation: Which reactive oxygen species are being
      measured?
AB  - The oxidative burst in circulating polymorphonuclear leukocytes (PMN) plays a
      fundamental role in pulmonary defense and injury. Flow cytometric techniques have
      been developed for quantitation of oxidative burst activity at the single cell
      level using 2',7'-dichlorofluorescin (DCFH). However, the specific reactive
      oxidant species being measured using this method are not clearly defined.
      Isolated human PMN were loaded with DCFH diacetate, stimulated with phorbol
      myristate acetate (PMA) in the presence or absence of specific reagents, and
      analyzed using flow cytometry. Addition of PMA resulted in a 90-fold increase in
      the fluorescence intensity of DCFH-loaded neutrophils (p <.01). Inhibition of
      NADPH oxidase activity using a calmodulin antagonist (W-13) decreased PMA-induced
      DCFH oxidation by 70% (p <.05). Inhibition of nitric oxide synthase using N(G)
      monomethyl-L-arginine (NMMA) did not significantly reduce DCFH oxidation, and did
      not alter the action of W-13. Addition of superoxide dismutase (SOD) had no
      effect, but catalase, with or without SOD, suppressed DCFH oxidation by 90% (p
      <.01). These data suggest that hydrogen peroxide, and not NO, is primarily
      responsible for the PMA-induced oxidation of DCFH in human PMN under these
      conditions.

PMID- 11445889
TI  - Effect of ECE and NEP inhibition on cigarette smoke-induced cell proliferation in
      the rat lung.
AB  - To investigate the role of endothelins in cigarette smoke-induced cell
      proliferation, we assessed the effect of two dual nonselective neutral
      endopeptidase (NEP)/endothelin-converting enzyme (ECE) inhibitors, phosphoramidon
      and CGS 26303, and of a specific NEP inhibitor, CGS 24592, on cell proliferation
      in the airways and arterial vasculature of the rat lung. Eight groups of rats
      were exposed to either room air (group 1, control), the smoke of 10 cigarettes
      (group 2, smoke only) or groups 1 and 2 in addition to a continuous iv infusion
      of CGS 24592, CGS 26303, or phosphoramidon (10 mg/kg/24 h). Cigarette smoke
      produced significant cell proliferation in the airways (epithelium and wall) and
      in the perialveolar ductular vessels (endothelium and wall). CGS 26303 reduced
      the smoke-induced proliferation in the endothelium and walls of the vessels
      adjacent to the alveolar ducts, and in the airway walls, but did not affect
      proliferation in the airway epithelium. CGS 24592 reduced cell proliferation in
      the airway wall. Phosphoramidon had no effect. These findings indicate that acute
      cigarette smoke-induced cell proliferation of the rat airways and pulmonary
      arterial vessels is mediated, at least in part, through release and actions of
      endothelins. The effectiveness of the more potent inhibitor, CGS 26303, appears
      to conform to its site of predominant expression.

PMID- 11445890
TI  - Inhalation toxicity of 1,6-hexamethylene diisocyanate homopolymers (HDI-IC and
      HDI-BT): results of subacute and subchronic repeated inhalation exposure studies.
AB  - This article addresses results of two 13-wk inhalation toxicity studies in Wistar
      rats with aerosolized 1,6-hexamethylene diisocyanate (HDI) homopolymers using
      either the isocyanurate (HDI-IC) type or biuret (HDI-BT) type. Groups of 10
      rats/sex/level were exposed nose-only to breathing zone concentrations of 0.5,
      3.3, and 26.4 mg HDI-IC/m(3) or 0.4, 3.4, and 21.0 mg HDI-BT/m(3) (MMAD = 1.4-3.3
      microm). The exposure regimen was 6 h/day, 5 days/wk for 13 wk. Two control
      groups were used in each study; one was exposed to filtered air, and the other to
      the vehicle acetone. In subacute pilot studies, groups of rats were exposed under
      identical conditions for 3 consecutive weeks using concentrations of
      approximately 4, 15-18, and 77-90 mg homopolymer/m(3). All studies demonstrated
      that adverse effects were caused by irritation-related responses occurring
      predominantly in the lower respiratory tract. Following subchronic exposure,
      compound-related effects were found only at the highest concentrations used and
      were confined to mild respiratory distress, marginally decreased body weights,
      and increased lung weights. Hematological evaluation showed a marginal increase
      in leukocyte counts. Pulmonary function testing revealed minimal changes
      indicative of increases in functional residual capacity and total lung capacity
      but without evidence of increased bronchial hyperreactivity to acetylcholine
      aerosol. Histopathology demonstrated an increased recruitment of alveolar
      macrophages, focal interstitial fibrosis with round-cell infiltrations, and
      bronchiolo-alveolar proliferations at the high-level exposure groups. The no
      observable-adverse-effect levels (NOAELs) of both the 3- and 13-wk studies were
      in the range of 3-4 mg/m(3). Appreciable differences between the two types of
      polyisocyanates were not observed.

PMID- 11445891
TI  - Toxicokinetics of inhaled benzo[a]pyrene: plasma and lung bioavailability.
AB  - Bioavailability and toxicokinetic studies are essential in order to establish
      dose-response relationships of widely distributed environmental toxicants such as
      benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon. Fischer 344 rats were
      exposed for 4 h (via nose-only inhalation) to aerosol exposure concentrations of
      0.1, 1.0, and 2.5 mg/m(3) of BaP absorbed onto carbon black particles using a
      state-of-the-art model aerosol generation system. Nominal and chamber
      concentrations of the particulate aerosol were determined gravimetrically with a
      seven-stage cascade impactor. The average aerosol for the 3 exposure
      concentrations used in this study exhibited a trimodal distribution with 93%
      cumulative mass less than 15.85 microm, 89% cumulative mass less than 10 microm,
      55.3% cumulative mass less than 2.5 microm, and 38% less than 1 microm. Fifty
      five percent of the aerosol had a cumulative mass less than PM(2.5) and the mass
      median aerodynamic diameter (MMAD) -/+ geometric standard deviation (GSD) for
      this mode was 1.7 -/+ 0.085 microm. Plasma and lung samples were collected at 30,
      60, 120, and 240 min postexposure. The concentrations of BaP parent compound and
      metabolites were determined by high-performance liquid chromatography. The
      toxicokinetic parameters were computed from the time course of plasma BaP
      concentration. The bioavailability of BaP increased as a function of exposure
      concentration, and toxicokinetic analysis indicates first-order pharmacokinetics
      for BaP. However, some toxicokinetic parameters such as clearance and volume of
      distribution remained constant throughout the duration of the postexposure
      period. BaP and its metabolite concentrations in plasma peaked at 1 h
      postexposure. At 240 min postexposure, only trace levels of BaP remained in the
      plasma. The BaP metabolites in the lung showed an identical trend where no parent
      compound was detected. Among the metabolites detected, BaP 4,5-, 7,8-, and 9,10
      dihydrodiols, 3-OH-BaP, and 9-OH-BaP were predominant.

PMID- 11445892
TI  - Dr. Mary Amdur Memorial Lecture.

PMID- 11445893
TI  - Proteomics of gluten: mapping of subunit 1 Ax2* in Cheyenne cultivar by matrix
      assisted laser desorption/ionization.
AB  - This paper reports results on the verification of the 1Ax2* high molecular weight
      glutenin subunit sequence in Cheyenne cultivar. The gene sequence of the protein
      is known but recently some text changes have been made, and furthermore until now
      no characterization of post-translational modifications has been reported. The
      two published sequences, named I and II, differ in four residues at positions 23,
      208, 475, and 611. The first sequence contains 20 Arg and 6 Lys residues,
      producing 26 tryptic fragments, since the Arg(109)-Pro(110) bond is generally not
      cleaved by trypsin. The second sequence contains 19 Arg and 6 Lys residues,
      producing 25 tryptic peptides, again because of the Arg(109)-Pro(110) bond. Both
      sequences generate two cyanogen bromide fragments. Matrix-assisted laser
      desorption/ionization analysis of the tryptic digest of the high-MW glutenin
      subunit 1Ax2* resulted in the identification of 24 out of the 26 expected
      peptides for sequence I, a sequence coverage of 99.5%. These results were
      sufficient to rule out sequence II and any protein glycosylation and any other
      post-translational modifications to within the detection limits of the method. It
      was found that the choice of matrix considerably influenced the sequence coverage
      in peptide mapping.

PMID- 11445894
TI  - Preparation of starch and other carbon fractions from higher plant leaves for
      stable carbon isotope analysis.
AB  - The measurement of the carbon isotope composition of starch and cellulose still
      relies on chemical isolation of these water-insoluble plant constituents and
      subsequent elemental analysis by isotope ratio mass spectrometry (EA/IRMS) of the
      purified fractions, while delta(13)C values of low-molecular-weight organic
      compounds are now routinely measured by gas chromatography/combustion/isotope
      ratio mass spectrometry (GC/C/IRMS). Here we report a simple and reliable method
      for processing milligram quantities of dried plant material for the analysis of
      the carbon isotope composition of lipids, soluble sugars, starch and cellulose
      from the same sample. We evaluated three different starch preparation methods,
      namely (1) enzymatic hydrolysis by alpha-amylase, (2) solubilization by dimethyl
      sulfoxide (DMSO) followed by precipitation with ethanol, and (3) partial
      hydrolysis by HCl followed by precipitation of the resulting dextrins by ethanol.
      Starch recovery for three commercially available native starches (from potato,
      rice and wheat) varied from 48 to 81% for the techniques based on precipitation,
      whereas the enzymatic technique exhibited yields between 99 and 105%. In
      addition, the DMSO and HCl techniques introduced a significant (13)C
      fractionation of up to 1.9 per thousand, while the carbon isotope composition of
      native starches analyzed after enzymatic digestion did not show any significant
      difference from that of untreated samples. The enzymatic starch preparation
      method was then incorporated into a protocol for determination of delta(13)C
      signatures of lipids, soluble carbohydrates, starch and crude cellulose. The
      procedure is based on methanol/chloroform/water extraction of dried and ground
      leaf material. After recovery of the chloroform phase (lipid fraction), the
      methanol/water phase was deionized by ion exchange (soluble carbohydrate
      fraction) and the pellet treated with heat-stable alpha-amylase (starch
      fraction). The remaining insoluble material was subjected to solvolysis by
      diglyme (cellulose fraction). The method was shown to be applicable to foliar
      tissues of a variety of different plant species (spruce, erect brome, maize and
      soybean).

PMID- 11445895
TI  - Facile sequencing of oligosaccharides by matrix-assisted laser
      desorption/ionisation on a hybrid quadrupole orthogonal acceleration time-of
      flight mass spectrometer.
AB  - N-Linked oligosaccharide mixtures released from a number of standard
      glycoproteins were derivatised with 3-acetylamino-6-acetylaminoacridine (AA-Ac)
      using reductive amination. Analysis of these mixtures using an experimental
      matrix-assisted laser desorption/ionisation (MALDI) hybrid quadrupole orthogonal
      acceleration time-of-flight (Q-TOF) mass spectrometer provided detailed
      information about the mass distribution of the glycan derivatives. Collision
      induced dissociation of the singly protonated [M + H](+) ions also gave rise to a
      number of product ions produced by the sequential cleavage of the glycosidic
      linkages. As fragmentation of the positively charged species occurred
      predominantly in one direction, i.e., from the non-reducing end of the glycan to
      the AA-Ac moiety, a considerable amount of information could be obtained with
      ease about the sequence in which the sugar residues were attached to one another.
      This derivatisation procedure and mass spectrometric methodology were applied
      successfully to neutral and acidic glycans released from proteins separated by
      gel electrophoresis.

PMID- 11445896
TI  - Analysis of carrageenans by matrix-assisted laser desorption/ionization and
      electrospray ionization mass spectrometry. I. kappa-Carrageenans.
AB  - Matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization
      (ESI) mass spectra of small kappa-carrageenans are reported and discussed. MALDI
      spectra can be obtained in both positive and negative ion mode. In the absence of
      extraneous metal ions, positive ions are formed by the attachment of one Na(+)
      ion to the carrageenan, whereas for negative ions one Na(+) ion is detached from
      the sulfate group. Multiply charged species are not observed in MALDI. Intense
      ESI spectra can be obtained in negative ion mode and now multiply charged species
      are seen. Alkali exchange experiments show that in these small carrageenan anions
      one, but only one, alkali metal ion is bound in a bidentate coordination with two
      ionic sulfate groups. G2-type ab initio calculations on model ions HO(-) [M(+)] (
      )OH (M = Li, Na, K, Cs), as well as arguments based on a simple Coulombic
      interaction model, show that the bidentate stabilization energy drops rapidly as
      the size of the alkali cation increases. Exchange of Na(+) with Li(+) leads to
      expulsion of the Na(+) ion generating, in ESI, intense multiply charged anions.
      An attempt is made to rationalize this behavior in terms of hydration effects.

PMID- 11445898
TI  - Screening combinatorial libraries for optimal enzyme substrates by mass
      spectrometry.
AB  - A method has been developed for the rapid identification of optimal enzyme
      substrates from combinatorial libraries. This methodology was validated by
      screening a 361-member N-terminally formylated tripeptide library, f-XXR (X = 19
      different amino acids), for optimal substrates of Escherichia coli peptide
      deformylase (PDF). The library was synthesized on a solid phase via the split
      pool synthesis method. The N-terminal formyl group was added by treating the
      resin with a 1:1 (mol/mol) mixture of HCO(2)H and DCO(2)D in the presence of
      dicyclohexylcarbodiimide. In a mass spectrum, each member of the library produced
      a doublet peak (separated by 1.0063 Da). Limited treatment of this library with
      E. coli PDF resulted in the deformylation of those peptides that are the most
      efficient substrates of the enzyme. The deformylated products, due to loss of the
      mass-degenerate formyl group, each generated a singlet peak in the mass spectrum.
      Thus, the PDF product peaks were readily identified and sequenced via tandem mass
      spectrometry. The results showed that PDF strongly prefers a norleucine and, to a
      lesser extent, a phenylalanine as the N-terminal residue, whereas it has little
      selectivity at the penultimate position. This result is in excellent agreement
      with the literature data and therefore demonstrates the methodology as an
      effective approach to the identification of optimal enzyme substrates. This
      method should be generally applicable to other enzymes as well as synthetic
      catalysts.

PMID- 11445899
TI  - A new technique for unbiased external ion accumulation in a quadrupole two
      dimensional ion trap for electrospray ionization Fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - External ion accumulation in a two-dimensional (2D) multipole trap has been shown
      to increase the sensitivity, dynamic range and duty cycle of a Fourier transform
      ion cyclotron resonance (FTICR) mass spectrometer. However, it is important that
      trapped ions be detected without significant bias at longer accumulation times in
      the external 2D multipole trap. With increasing ion accumulation time pronounced
      m/z discrimination was observed when trapping ions in an accumulation quadrupole.
      In this work we show that superimposing lower rf-amplitude dipolar excitation
      over the main rf-field in the accumulation quadrupole results in disruption of
      the m/z discrimination and can potentially be used to achieve unbiased external
      ion accumulation with FTICR.

PMID- 11445900
TI  - Separation and characterisation of five polar herbicides using countercurrent
      chromatography with detection by negative ion electrospray ionisation mass
      spectrometry.
AB  - Five polar herbicides were separated and characterised using high-speed
      analytical countercurrent chromatography (HSACCC) in conjunction with online
      electrospray mass spectrometry (ESI-MS). The countercurrent chromatography used a
      standard isocratic biphasic solvent system of hexane/ethyl acetate/methanol/water
      in reverse phase to effect the separation of these five environmentally important
      compounds. The chromatograph was coupled to a triple quadrupole mass spectrometer
      via a standard electrospray liquid chromatography interface that was able to give
      mass spectra in negative ion mode of each compound. Limits of detection are
      reported for this series of compounds along with representative negative ion ESI
      MS data and calibrations for the separation.

PMID- 11445901
TI  - Coupling of a supercritical fluid chromatography system to a hybrid (Q-TOF 2)
      mass spectrometer: on-line accurate mass measurements.
AB  - This note describes a simple and economical method to couple a supercritical
      fluid chromatography (SFC) system (Berger Instruments, US) with a high-resolution
      hybrid mass spectrometer (Q-TOF 2; Micromass, UK). This experimental arrangement
      has three distinct advantages: (1) coupling between the two systems can be
      effected without the need for an interface or hardware modifications of either
      system, (ii) this experimental arrangement provides on-line accurate mass SFC/MS
      measurements which are indispensable for the characterisation of new chemical
      entities and unknown metabolites, and (iii) the characteristically fast spectral
      acquisition rate of the time-of-flight (TOF) analyser renders the present
      arrangement an important contribution to future semipreparative fraction
      collection setups which use mass spectrometry as a detector.

PMID- 11445902
TI  - Growth hormone abuse in the horse: preliminary assessment of a mass spectrometric
      procedure for IGF-1 identification and quantitation.
AB  - Previous studies have shown that insulin-like growth factor 1 (IGF-1) is a
      promising marker for the detection of growth hormone (GH) abuse in the horse. The
      significant increases observed with GH administration in comparison to natural
      levels imply the possibility of setting a threshold level for IGF-1 that would be
      indicative of GH abuse. Although an immunoradiometric assay (IRMA) has been
      identified as a reliable screening method, a more specific IGF-1 quantification
      method needs to be developed for the prosecution of GH abuse by horseracing
      authorities. This study describes such an HPLC electrospray mass spectrometry
      (LC/ESI-MS) method that was developed and then assessed for the specific analysis
      of IGF-1 at the low levels encountered in serum. The structural identity of IGF-1
      was confirmed by endoproteinase Asp-N digestion followed by LC/MS and LC/MS/MS
      characterisation. This was followed by quantification of IGF-1 as the intact
      molecule against an internal standard.

PMID- 11445904
TI  - Simultaneous assessment of cholesterol absorption and synthesis in humans using
      on-line gas chromatography/ combustion and gas chromatography/pyrolysis/isotope
      ratio mass spectrometry.
AB  - A number of dietary components and drugs are known to inhibit the absorption of
      dietary and biliary cholesterol, but at the same time can compensate by
      increasing cholesterol synthesis. It is, therefore, necessary to have a
      convenient and accurate method to assess both parameters simultaneously. Hence,
      we validated such a method in humans using on-line gas
      chromatography(GC)/combustion and GC/pyrolysis/isotope-ratio mass spectrometry
      (IRMS). Cholesterol absorption was measured using the ratio of [(13)C]cholesterol
      (injected intravenously) to [(18)O]cholesterol (administered orally).
      Simultaneously, cholesterol synthesis was measured using the deuterium
      incorporation method. Our methodology was applied to 12 mildly
      hypercholesterolemic men that were given a diet providing 2685 +/- 178 Kcal/day
      (mean +/- SD) and 255 +/- 8 mg cholesterol per day. Cholesterol fractional
      synthesis rates ranged from 5.0 to 10.5% pool/day and averaged 7.36% +/- 1.78%
      pool/day (668 +/- 133 mg/day). Cholesterol absorption ranged from 36.5-79.9% with
      an average value of 50.8 +/- 15.4%. These values are in agreement with already
      known data obtained with mildly hypercholesterolemic Caucasian males placed on a
      diet similar to the one used for this study. However, our combined IRMS method
      has the advantage over existing methods that it enables simultaneous measurement
      of cholesterol absorption and synthesis in humans, and is therefore an important
      research tool for studying the impact of dietary treatments on cholesterol
      parameters.

PMID- 11445905
TI  - Differential stable isotope labeling of peptides for quantitation and de novo
      sequence derivation.
AB  - We have demonstrated the use of per-methyl esterification of peptides for
      relative quantification of proteins between two mixtures of proteins and
      automated de novo sequence derivation on the same dataset. Protein mixtures for
      comparison were digested to peptides and resultant peptides methylated using
      either d0- or d3-methanol. Methyl esterification of peptides converted carboxylic
      acids, such as are present on the side chains of aspartic and glutamic acid as
      well as the carboxyl terminus, to their corresponding methyl esters. The separate
      d0- and d3-methylated peptide mixtures were combined and the mixture subjected to
      microcapillary high performance liquid chromatography/tandem mass spectrometry
      (HPLC/MS/MS). Parent proteins of methylated peptides were identified by
      correlative database searching of peptide tandem mass spectra. Ratios of proteins
      in the two original mixtures could be calculated by normalization of the area
      under the curve for identical charge states of d0- to d3-methylated peptides. An
      algorithm was developed that derived, without intervention, peptide sequence de
      novo by comparison of tandem mass spectra of d0- and d3-peptide methyl esters.

PMID- 11445906
TI  - Determination of the disulfide bond pattern of the endogenous and recombinant
      angiogenesis inhibitor endostatin by mass spectrometry.
AB  - Endostatin, a C-terminal fragment of collagen XVIII, is a promising protein drug
      which is in development for cancer therapy due to its anti-angiogenic activity.
      Although several endogenous molecular forms of human endostatin differing in
      their N-terminal length and their post-translational modifications (18.5-22 kDa)
      have been discovered, only one recombinant form of 20 kDa is used in clinical
      trials. This protein, recombinantly expressed in Pichia pastoris, contains four
      cysteines forming two disulfide bonds (Cys1-Cys4 and Cys2-Cys3). In contrast,
      there are conflicting data about the disulfide pattern of endogenous material.
      This report presents the disulfide analyses of both the endogenous circulating
      endostatins isolated from human hemofiltrate and the recombinant protein. The
      determination of the disulfide pattern was performed by Edman degradation, matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOFMS) and electrospray ionization ion trap mass spectrometry (ESI-ITMS)
      performed in the off-line nanospray mode. All native and recombinant endostatins
      exhibited a Cys1-Cys4 (Cys(162)-Cys(302)) and Cys2-Cys3 (Cys(264)-Cys(294))
      linkage. For a clear discussion of fragmented disulfide-bridged peptide chains
      obtained from MS(n) experiments, a modified general nomenclature is proposed.

PMID- 11445907
TI  - Rapid and sensitive quantitation of antibiotics in fermentations by electrospray
      mass spectrometry.
AB  - Electrospray ionisation mass spectrometry (ESI-MS) has been used for the
      determination and quantitation of a broad range of 24 antibiotics, from groups
      including aminoglycosides, beta-lactams, tetracyclines, antifungals and
      glycopeptides. Spectra have been acquired for all 24 antibiotics derived from
      pure samples dissolved in acetonitrile/water, along with samples extracted from
      complex fermentation liquor. Quantitation was carried out by the detection of the
      protonated molecules, using time-scheduled single-ion monitoring (SIM). ESI-MS
      was used to detect and quantify to 5-microM levels. A one-step extraction of
      antibiotics with an organic solvent (methanol) was used for this rapid and simple
      procedure. Specificity is not matched by other methods and antibiotic analogues
      (e.g. the five forms of erythromycin) can be determined within minutes.

PMID- 11445910
TI  - In situ study of sucrose exposure, mutans streptococci in dental plaque and
      dental caries.
AB  - The purpose of this study was to investigate the relationship among frequency of
      sucrose exposure, mutans streptococci levels and dental caries. Adult volunteers
      took part in this crossover study performed in 4 phases of 28 days each. The
      volunteers wore intra-oral palatal appliances containing blocks of human dental
      enamel and dripped 20% sucrose solution onto the dental blocks from 0 to 8
      times/day. After each phase, the colony forming units (CFU) were determined in
      dental plaque and enamel dental caries was evaluated using cross-sectional
      hardness. Sucrose frequency had no statistically significant effect on mutans
      streptococci levels. In the enamel cross-sectional hardness tests, significant
      differences (p < 0.05) in relation to area of mineral loss were observed only
      when sucrose exposure was 8 times/day. Similar results were obtained when cross
      sectional hardness was assessed at each distance from enamel surface.

PMID- 11445911
TI  - Phenotypic stability and plasmid detection in Actinobacillus
      actinomycetemcomitans.
AB  - The stability of hemolytic activity, antibiotic resistance and plasmid detection
      in Actinobacillus actinomycetemcomitans isolates were studied. These
      characteristics were stable for all experimental conditions. All tested isolates
      lost or changed some phenotypic characteristics such as colonial morphology and
      growth in liquid medium.

PMID- 11445912
TI  - Healing process of dog dental pulp after pulpotomy and pulp covering with mineral
      trioxide aggregate or Portland cement.
AB  - Considering several reports about the similarity between the chemical
      compositions of the mineral trioxide aggregate (MTA) and Portland cement (PC),
      the subject of this investigation was to analyze the behavior of dog dental pulp
      after pulpotomy and direct pulp protection with these materials. After pulpotomy,
      the pulp stumps of 26 roots of dog teeth were protected with MTA or PC. Sixty
      days after treatment, the animal was sacrificed and the specimens removed and
      prepared for histomorphological analysis. There was a complete tubular hard
      tissue bridge in almost all specimens. In conclusion, MTA and PC show similar
      comparative results when used in direct pulp protection after pulpotomy.

PMID- 11445913
TI  - Effect of isotretinoin on tooth germ and palate development in mouse embryos.
AB  - Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are
      currently used in dermatological treatments. The administration of high doses of
      this vitamin provokes congenital malformations in mice: cleft palate, maxillary
      and mandibular hypoplasia and total or partial fusion of the maxillary incisors.
      This study compares the tooth germs of the first maxillary and mandibular molars
      of fetal mice submitted to isotretinoin during organogenesis. Twelve 60-day-old
      female Mus musculus were divided into two groups on the 7th day of pregnancy:
      treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil,
      was administered from the 7th to the 13th day of pregnancy; control group-
      vegetable oil in equivalent volume was administered orally for the same period.
      On the 16th day of pregnancy, the females were sacrificed, the fetuses were
      removed and their heads amputated. After standard laboratory procedures, 6-micron
      thick serial slices were stained with hematoxylin and eosin for optical
      microscopy examination. The results showed that both groups had closed palates
      with no reminiscence of epithelial cells; however, the first molar germs of the
      isotretinoin-treated animals showed delayed development compared to the control
      animals.

PMID- 11445914
TI  - Clinical study of guided bone regeneration and/or bone grafts in the treatment of
      ligature-induced peri-implantitis defects in dogs.
AB  - This study evaluated, by clinical analysis, the hard tissue response following
      treatment of ligature-induced peri-implantitis defects in 5 dogs. The mandibular
      premolars were removed from both sides of the jaw. After 3 months of healing, two
      titanium implants were placed on each side of the mandible. Following abutment
      connection, 3 months later, experimental peri-implantitis was induced by the
      placement of cotton ligatures in a submarginal position. Ligatures and abutments
      were removed after one month and the bony defects were randomly assigned to one
      of the following treatments: debridement (DE), debridement plus guided bone
      regeneration (GBR), debridement plus mineralized bone graft (BG) and debridement
      plus guided bone regeneration associated with mineralized bone graft (GBR + BG).
      The peri-implant bone defects were clinically measured before and 5 months post
      treatment. Results showed a higher percentage of vertical bone fill for GBR + BG
      (27.77 +/- 14.07) followed by GBR (21.78 +/- 16.19), BG (21.26 +/- 6.87), DE
      (14.03 +/- 5.6). However, there were no statistically significant differences
      between any of the treatments proposed (one way repeated measures analysis of
      variance, P = 0.265).

PMID- 11445915
TI  - Dental anomaly: dens evaginatus (talon cusp).
AB  - Dens evaginatus is a developmental anomaly characterized by the occurrence of an
      extra cusp shaped as a tubercle projecting from the palatal or buccal surfaces
      (talon cusp). In the anterior dentition, dens evaginatus is more commonly found
      in the maxilla and on the palatal surface of the tooth. The authors present a
      case of dens evaginatus in a maxillary central incisor, in which the evagination
      was removed and routine endodontic treatment was performed.

PMID- 11445916
TI  - Intrauterine dentistry: an integrated model of prevention.
AB  - Intrauterine Dentistry is a highly relevant subject of our time. The use of
      preventive measures in the intrauterine stage can avoid several diseases, among
      these, dental caries. The WHO advises that from the 4th month of pregnancy, women
      should avoid the intake of sugar, so that the fetus, future child, does not
      develop an exaggerated attraction for these types of foods, thus being
      susceptible to caries. Through questionnaires sent to gynecologist-obstetricians
      and dentists, this research investigated the information they have about this
      subject and how they instruct their patients. Questionnaires were also sent to
      pregnant women requesting information about the instructions they had received
      for the prevention of oral diseases of their fetus. Seventy-one percent of the
      dentists and 80% of the gynecologist-obstetricians reported having instructed the
      pregnant women to reduce the intake of sugar. However, only 13.6% of the dentists
      and no gynecologist-obstetrician instructed the reduction of sugar intake between
      the 12th and 18th week of pregnancy. A total of 42.2% of the pregnant women
      referred to these instructions, but none received instruction as to the specific
      period of the 12th and 18th week. An ideal model of treatment for pregnant women
      must include integrated and multiprofessional treatment, in which general
      dentists and gynecologist-obstetricians work together with the participation of
      the patient.

PMID- 11445917
TI  - Effect of refrigeration on tensile bond strength of three adhesive systems.
AB  - The purpose of this study was to investigate the tensile bond strengths of three
      adhesive systems applied to dentin at refrigerated and room temperatures. Ninety
      bovine incisor teeth were obtained, embedded in self-cured acrylic resin, abraded
      on a lathe under water spray and polished to 400 and 600 grit to form
      standardized dentin surfaces before randomly assigning to six groups (n = 15).
      The adhesive systems Scotchbond Multi-Purpose, Single Bond and Prime & Bond NT
      were applied to dentin according to the manufacturers' instructions at
      refrigerated temperature (4 degrees C) and at room temperature (23 degrees C),
      before bonding resin-based composite (Z 100). The specimens were stored in
      distilled water at 37 degrees C for 24 hours and submitted to tensile bond
      strength tests on a universal testing machine (EMIC DL-2000) at a crosshead speed
      of 0.5 mm/min. The resulting data were statistically analyzed using analysis of
      variance and Tukey's test. No statistical differences were found when the
      adhesive systems were applied at refrigerated and room temperatures. Scotchbond
      Multi-Purpose and Single Bond had significantly stronger tensile bond strengths
      than Prime & Bond NT at room and refrigerated temperatures (p < 0.01). Scotchbond
      Multi-Purpose and Single Bond were statistically similar. No adverse effects upon
      tensile bond strength were observed when adhesive systems were taken directly
      from refrigerated storage.

PMID- 11445918
TI  - Two-dimensional photoelastic stress analysis of traumatized incisor.
AB  - In this study, stress of traumatized incisor and the effect of stress on tooth
      and alveolar bone was studied with two-dimensional photoelasticity. Two
      homogeneous two-dimensional maxillary central incisor models were prepared. Loads
      were applied to the labial side of incisal edge and middle third of the crown at
      angles of 45 degrees and 90 degrees. It was observed that stress was increased on
      teeth and alveolar bone when load was applied 90 degrees on labial side of
      incisal edge.

PMID- 11445919
TI  - Radiopacity of glass-ionomer/composite resin hybrid materials.
AB  - This study visually compared the radiopacity of seven restorative materials (3
      resin-modified glass-ionomer cements, 3 polyacid-modified composite resins, and 1
      conventional glass-ionomer cement) to a sound tooth structure sample, and an
      aluminium stepwedge. All hybrid materials were more radiopaque, except for one
      resin-modified glass-ionomer cement, than both the tooth structure and
      conventional glass-ionomer cement.

PMID- 11445920
TI  - Influence of the retention of antiseptic solution dyes on the translucence of
      glass-ionomer cements.
AB  - Due to the great importance that antiseptic solutions have on the control and
      prevention of oral diseases and their influence on the translucence of esthetic
      restorative materials, the present study evaluated the effect of antiseptic
      solutions on the translucence of two glass-ionomer cements, Vidrion R and Chelon
      Fil, at eight time periods. Four antiseptic solutions were used: Listerine,
      Malvona, Flogoral and Plax. Vidrion R was less translucent than Chelon Fil.
      Translucence decreased with longer observation time and Malvona caused the lowest
      translucence.

PMID- 11445921
TI  - Is this osteoporosis test for you?

PMID- 11445922
TI  - The other common prostate problem.

PMID- 11445923
TI  - A way out of the multivitamin maze.

PMID- 11445924
TI  - New tools to help you quit smoking.

PMID- 11445925
TI  - A brief history of cholesterol.

PMID- 11445926
TI  - I have a cardiac arrhythmia (heart rhythm irregularity) and medications haven't
      worked. Is surgery an option?

PMID- 11445927
TI  - Does drinking coffee inhibit calcium absorption?

PMID- 11445928
TI  - Non-aqueous potentiometry using zeolites.
AB  - Potentiometric investigations using pressed zeolite discs are reported. Potential
      measurements have been performed in non-aqueous solutions--this is the first
      report, to our knowledge, of potentiometric detection of ions in non-aqueous
      media with zeolite materials. Nernstian behaviour is also displayed in aqueous
      solutions for ions that are only able to penetrate a fraction of the internal
      volume of the zeolite employed.

PMID- 11445929
TI  - Selective determination of dopamine in the presence of ascorbic acid at an over
      oxidized poly(N-acetylaniline) electrode.
AB  - An over-oxidized poly(N-acetylaniline) (PNAANI)/GCE was used to determine
      dopamine (DA) in a large excess of ascorbic acid (AA) by differential pulse
      voltammetry. A linear relation between Ip and DA concentration was found over the
      range 5.0 x 10(-7) to 2.0 x 10(-5) M. The detection limit was 1.68 x 10(-8) M for
      S/N = 3 and 400 microM AA did not interfere with the DA determination. The high
      sensitivity was due to accumulation and selectivity was due to charge
      discrimination. The mechanism of selective determination of DA at over-oxidized
      PNAANI/GCE was also proposed.

PMID- 11445931
TI  - Molecularly imprinted polymers in analytical chemistry.

PMID- 11445930
TI  - Expression of results with uncertainty for the determination of pesticides in
      melon--experience in a proficiency test.
AB  - The expression of results with an uncertainty through the "bottom-up" approach,
      involving the estimation and combination of all the sources of uncertainty,
      represents a challenge when the analytical method includes mass transfer steps
      (MTS). These steps (e.g. extraction, evaporation, digestion, etc.) with
      inherently different from 100% recoveries lack models capable of describing their
      precision and efficiency. Recently, a new methodology was published aimed at the
      estimation of the performance of these critical steps. Comparison of the
      experimental dispersion from the replicated analysis of spiked samples with the
      combination of the uncertainty associated with gravimetric, volumetric and
      instrumental quantification steps (described by well established models) allows
      the estimation of the MTS uncertainty. Evaluation of the behaviour of the MTS
      within the analytical range supports the use of developed estimations over a wide
      concentration range. This methodology was applied, with success, to the
      determination of pesticide residues in melon in one particular proficiency test
      organised by the Food Analysis Performance Assessment Scheme (FAPAS) between
      November 2000 and February 2001.

PMID- 11445932
TI  - An unexpected selectivity of a propranolol-derived molecular imprint for
      tamoxifen.
AB  - During the evaluation of molecular imprinted polymers (MIPs) prepared against the
      drug tamoxifen a propranolol-derived MIP was used as a positive control.
      Surprisingly the propranolol-derived MIP showed considerable selectivity towards
      tamoxifen, and was indeed much more selective than the MIP prepared using
      tamoxifen as the imprint molecule. The consequences of this unexpected, cross
      reactivity for the use of MIPs in analytical chemistry is discussed.

PMID- 11445933
TI  - Towards the development of molecularly imprinted artificial receptors for the
      screening of estrogenic chemicals.
AB  - Molecularly imprinted polymers are prepared using various steroid compounds as
      the templates. The imprinted polymers can selectively re-bind the original print
      molecules, which leads to versatile potential applications. The feasibility of
      using these artificial receptors to replace their biological counterparts for
      preliminary screening of a chemical library is demonstrated. A steroid library
      composed of 22 closely related compounds is screened with an estrogen specific
      polymer. The print molecule is identified with accuracy and structural
      similarities of other members are correlated with normalized retention indices.
      Molecularly imprinted artificial receptors are envisioned as being useful for
      screening purposes in drug discovery or for identifying endocrine-disrupting
      chemicals.

PMID- 11445934
TI  - Synthetic receptors as sensor coatings for molecules and living cells.
AB  - Non-covalent molecularly imprinted polymers are applied as sensitive coatings to
      planar waveguides and mass-sensitive devices for the selective detection of
      various groups of analytes in the gaseous and aqueous phases. Cavity imprinting
      in the bulk of the sensor material as well as surface imprinting techniques are
      used to enrich analytes ranging from sub-nanometres to micrometres in analyte
      size. The coated devices provide sensitivity to e.g. polycyclic aromatic
      hydrocarbons, xanthine derivatives, complex coffee samples and whole
      microorganisms.

PMID- 11445935
TI  - Synthesis of 5-fluorouracil-imprinted polymers with multiple hydrogen bonding
      interactions.
AB  - The antitumor active compound 5-fluorouracil (5-FU) was used as a target molecule
      and 5-FU-imprinted polymers were synthesized using 2,6-bis(acrylamido)pyridine
      and/or 2-(trifluoromethyl)acrylic acid as functional monomers. The 5-FU-imprinted
      polymers showed a higher affinity for 5-FU than that for 5-FU derivatives. By
      using both functional monomers simultaneously, the affinity and separation for 5
      FU were improved.

PMID- 11445936
TI  - Novel polymeric membranes having chiral recognition sites converted from
      tripeptide derivatives.
AB  - Six kinds of tripeptide derivative consisting of L-glutamic acid gamma-benzyl
      ester [Glu(OBzl)] (E) and L-phenylalanine (Phe) (F), i.e. EEF, EFE, FEE, FEF, FFE
      and FFF, were converted into chiral recognition sites by adopting Boc-L-Trp as a
      print molecule. The formed chiral recognition sites discriminated between Ac-L
      Trp and the corresponding D-isomer, and the L-isomer was incorporated into the
      membrane in preference to the D-isomer. The affinity constants between the
      recognition site formed in each membrane and Ac-L-Trp were determined to be 9.6 x
      10(3) to 8.4 x 10(3) mol-1 dm3. The affinity constant depends on both the
      tripeptide sequence and the amino acid residue content. Tripeptide derivatives
      containing more glutamic acid derivative residues or glutamic acid derivative as
      an amino-terminal residue show higher affinity constants.

PMID- 11445937
TI  - Effect of solvent composition on chiral recognition ability of molecularly
      imprinted DIDE derivatives.
AB  - In the present study, molecularly imprinted materials from the tetrapeptide
      derivative, H-Asp(OcHex)-Ile-Asp(OcHex)-Glu(OBzl)-CH2-, were adopted as samples
      to study the effect of the polarity of the environment on the chiral (molecular)
      recognition ability. The optimum composition, with the best chiral recognition,
      is a 50 vol% aqueous ethanol solution.

PMID- 11445938
TI  - Evaluation of methods aimed at complete removal of template from molecularly
      imprinted polymers.
AB  - Polymers imprinted with clenbuterol were used to study the influence of various
      post-polymerization treatments [e.g., thermal annealing, microwave assisted
      extraction (MAE), Soxhlet extraction and supercritical fluid template desorption]
      on the bleeding of residual template. The aim of the study was to reduce the
      bleeding to levels that would allow the use of the materials as affinity phases
      for extraction of clenbuterol from bovine urine at concentrations below 1 ng ml
      1. After treatment, the clenbuterol imprinted polymers were packed into solid
      phase extraction columns and the bleeding was estimated by quantifying the amount
      of template released in 10 ml of methanol-acetic acid (9 + 1 v/v). This was
      followed by an assessment of selectivity and recovery in comparison with non
      treated material. The lowest bleeding level was found after MAE using 100%
      trifluoroacetic acid for 3 x 20 min at 100 degrees C. The collected eluate
      contained in this case 3 ng ml-1 of clenbuterol. The same material was
      subsequently used for the extraction of clenbuterol from spiked bovine urine. The
      resulting selectivity and recovery were lower compared with those obtained using
      the untreated material. A milder but still efficient method to reduce the
      bleeding level was found to be MAE with formic acid. In this case a bleeding
      level of 14 ng ml-1 was found after only a 1 h extraction time. In a second model
      system, using a polymer imprinted with L-phenylalanine anilide, the bleeding was
      reduced to a similar level by extensive on-line washing in good swelling solvents
      containing acid or base additives and after thermal annealing of the polymers in
      the dry state.

PMID- 11445939
TI  - Systematic study of steric and spatial contributions to molecular recognition by
      non-covalent imprinted polymers.
AB  - Although molecular imprinting is a widely accepted method for producing template
      specific polymers, the general rules for prediction and control of the binding
      and catalytic properties of these materials are still not fully understood. One
      reason for this is the problematic structural analysis of the active sites in the
      polymers, which are not amenable to X-ray crystallography or microscopic
      techniques due to their amorphous and heterogeneous nature. Therefore, molecular
      probes have been the most informative agents for the analysis of the structure of
      active sites. This paper focuses on the steric and geometrical aspects of shape
      recognition in non-covalent imprinted polymers, with particular effort to
      minimize other factors contributing to molecular recognition by the polymers.
      Chiral amine compounds with systematic changes in spatial, distal and
      conformational components of sterically controlled molecular recognition were
      investigated for use as non-covalent imprinted polymers. Chromatographic studies
      revealed that steric and spatial interactions influence the selectivity
      properties of imprinted polymers in a predictable fashion.

PMID- 11445940
TI  - Molecularly imprinted polymer sensors for pesticide and insecticide detection in
      water.
AB  - Antibodies, peptides, and enzymes are often used as molecular recognition
      elements in chemical and biological sensors. However, their lack of stability and
      signal transduction mechanisms limits their use as sensing devices. Recent
      advances in the field of molecularly imprinted polymers (MIPs) have created
      synthetic materials that can mimic the function of biological receptors but with
      less stability constraints. These polymers can provide high sensitivity and
      selectivity while maintaining excellent thermal and mechanical stability. To
      further enhance the advantages of the traditional imprinted polymer approach, an
      additional fluorescent component has been introduced into these polymers. Such a
      component provides enhanced chemical affinity as well as a method for signal
      transduction. In this type of imprinted polymer, binding of the target analyte
      invokes a specific spectral signature from the reporter molecule. Previous work
      has provided molecularly imprinted polymers that are selective for the hydrolysis
      products of organophosphorus species such as the nerve agents sarin and soman.
      (A. L. Jenkins, O. M. Uy and G. M. Murray, Anal. Chem., 1999, 71, 373). In this
      paper the direct imprinting of non-hydrolyzed organophosphates including
      pesticides and insecticides is described. Detection limits for these newly
      developed MIP sensors are less than 10 parts per trillion (ppt) with long linear
      dynamic ranges (ppt to ppm) and response times of less than 15 min.

PMID- 11445941
TI  - Thin layer molecularly imprinted microfiltration membranes by
      photofunctionalization using a coated alpha-cleavage photoinitiator.
AB  - A novel approach towards thin-layer molecularly imprinted polymer (MIP) composite
      membranes was developed based on using benzoin ethyl ether (BEE), a very
      efficient alpha-scission photoinitiator. The triazine herbicide desmetryn was
      used as the template, and a mixture of the functional monomer 2-acrylamido-2
      methyl-1-propane sulfonic acid (AMPS) and the cross-linker N,N'-methylene-bis
      acrylamide (MBAA) in methanol was copolymerised via photoinitiation followed by
      deposition on the surface of either hydrophobic or hydrophilically precoated
      polyvinylidene fluoride (PVDF) microfiltration membranes. Blanks were prepared
      under identical conditions, but without the template. Especially, the degree of
      functionalization (DF) of the PVDF membranes with poly(AMPS-co-MBAA), the
      membrane permeabilities and non-specific vs. MIP-specific template binding from
      aqueous solutions during fast filtration were studied in detail to evaluate the
      effects of the preparation conditions, in particular the coating of the membrane
      surface with the photoinitiator prior to UV irradiation and the influence of the
      precoated hydrophilic layer on PVDF. Significant template specificities of the
      MIP membranes compared with the blanks were only achieved for the preparations
      including coating the two types of PVDF membranes with BEE. In contrast, a
      homogeneous photoinitiation of the copolymerisation in the membrane pore volume
      yielded functional layers with similar DF but with only non-specific desmetryn
      binding. All data clearly indicate the significant contribution of MIP
      stabilization by the support material in layers of optimum thickness to the MIP
      specificity. Main advantages of the novel approach are the potential to
      synthesize MIP composite membranes by controlled deposition onto any kind of
      polymer support, and the very fast MIP preparations due to a very efficient
      photoinitiator and small MIP layer thickness. Due to the mechanical and chemical
      stability in combination with high permeabilities, thin-layer MIP composite
      membranes have a large application potential, e.g., in solid phase extraction.

PMID- 11445942
TI  - Chemiluminescent flow-through sensor for 1,10-phenanthroline based on the
      combination of molecular imprinting and chemiluminescence.
AB  - A functional polymer for the catalysis of the chemiluminescent reaction and
      molecular recognition ability of 1,10-phenanthroline was prepared based on the
      molecular imprinting method. The structural and catalytic roles of transition
      metal ion interactions were applied in the material design. A ternary complex, 4
      vinylpyridine-Cu(II)-1,10-phenanthroline (2:1:1), was synthesized and used as a
      functional monomer. The ligand 1,10-phenanthroline in the ternary complex was the
      template used to form the molecularly imprinted polymer. Another monomer,
      styrene, and the cross-linking reagent divinylbenzene were copolymerized with the
      ternary complex. The polymer containing the ternary complex is an efficient
      catalyst for the decomposition of hydrogen peroxide. During the hydrogen peroxide
      decomposition, superoxide radical ion is formed, which reacts with 1,10
      phenanthroline and gives a chemiluminescent emission. The 1,10-phenanthroline was
      destroyed during the chemiluminescent reaction, leaving a cavity and copper
      binding sites for another 1,10-phenanthroline molecule. The prepared polymer
      particles were packed into a glass tube and developed as a molecular recognition
      chemiluminescent flow-through sensor for 1,10-phenanthroline. The sensitivity and
      selectivity of the sensor were tested.

PMID- 11445943
TI  - Simultaneous determination of twelve tea catechins by high-performance liquid
      chromatography with electrochemical detection.
AB  - A high-performance liquid chromatographic method with electrochemical detection
      was developed for the determination of twelve tea catechins including four major
      catechins: epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG)
      and epigallocatechin gallate (EGCG); four of their epimers at the C-2 position,
      C, GC, CG and GCG; and four methylated catechin derivatives, epigallocatechin-3-O
      (3-O-methyl)gallate, gallocatechin-3-O-(3-O-methyl)gallate, epigallocatechin-3-O
      (4-O-methyl)gallate and epicatechin-3-O-(3-O-methyl)gallate. These catechins were
      separated on an ODS C18 reversed-phase column by isocratic elution with 0.1 M
      NaH2PO4 buffer (pH 2.5)-acetonitrile (87:13) containing 0.1 mM EDTA.2Na. The
      detection limits (S/N = 3) of these catechins were approximately 10-40 pmol ml-1
      at an applied voltage of 600 mV. Extracting these catechins from tea leaf powder
      with H2O-acetonitrile (1:1) at 30 degrees C for 40 min inhibited the
      epimerization at C-2 significantly from these epicatechins compared to extraction
      with hot water at 90 degrees C. This analytical method is sensitive to and
      appropriate for the simultaneous determination of various biologically active
      catechins in green tea.

PMID- 11445944
TI  - High-resolution determination of H+ by ion chromatography. Application to the
      simultaneous determination of H+, Na+, NH4+ and K+ in acid rain.
AB  - An ion chromatographic (IC) method was developed for the high-resolution
      determination of a sample's free hydrogen ion concentration (H+). Highly purified
      lithium dodecyl sulfate was used as the stationary phase, a slightly acidified
      aqueous LiCl solution was used as the mobile phase and conductivity was used for
      analyte detection. An electrical double layer (EDL) containing H+ was established
      on the stationary phase by using a slightly acidified electrolyte solution as the
      eluent. H+ in the EDL protonated any weak acid groups (i.e., silanols) on the
      stationary phase so that H+ from the sample could be retained/separated purely by
      dodecyl sulfate. The optimum molar ratio of H+:Li+ in the EDL for this IC system
      was obtained by using an aqueous solution containing 40.0 mM LiCl and 0.07 mM
      H2SO4 as the eluent. After separation, H+ was detected by direct conductimetric
      measurement. An H+ detection limit of better than 8.2 x 10(-6) M was obtained
      from the analysis of standard aqueous H2SO4 solutions. Other monovalent cations
      could also be separated with this method, giving detection limits of 7.4 x 10(
      5), 4.3 x 10(-5) and 4.2 x 10(-5) M for Na+, NH4+ and K+, respectively. The
      method was applied to the simultaneous determination of H+, Na+, NH4+ and K+ in
      acid rain. The results obtained showed a significant improvement in
      reproducibility when compared with those from a conventional pH-meter. Acid rain
      samples with a pH < 5 could be analyzed with this IC system.

PMID- 11445945
TI  - Determination of linear alkylbenzene sulfonates and their polar carboxylic
      degradation products in sewage treatment plants by automated solid-phase
      extraction followed by capillary electrophoresis-mass spectrometry.
AB  - Linear alkylbenzene sulfonates (LAS) were determined by solid-phase extraction
      (SPE), followed by capillary electrophoresis and mass spectrometry detection (CE
      MS). The linear range of the proposed method varied from 33 to 316 and from 215
      to 2057 micrograms L-1, depending on the compound, with limits of detection
      ranging from 4.4 to 23 micrograms L-1 when 200 ml of wastewater were
      preconcentrated. The analysis and confirmation of the polar carboxylic
      metabolites of LAS, the sulfophenyl carboxylic acids (SPC) was also achieved, and
      their presence was detected in both, influent and effluents of the sewage
      treatment plant (STP). [M - H]- ions were used for CE-MS confirmation and
      quantification. CE-MS diagnostic ions were the same ones used in LC-electrospray
      (ESI)-MS and corresponded to m/z 297, 311, 325 and 339 for C10LAS, C11LAS, C12LAS
      and C13LAS, respectively. For SPC identification, diagnostic ions corresponded to
      m/z 215 to 369 (with 14 mass unit steps) for C2 to C13SPC, respectively. LAS were
      determined in wastewater samples of the influent and effluent of three sewage
      treatment plants (STP), two of them using biological treatment with secondary
      settlement and receiving mainly domestic wastewater whereas one of the plants was
      operated with physiochemical treatment and received mainly industrial wastewater.
      The concentration levels of total LAS varied from 1000 to 1900 micrograms L-1 in
      the influents of STP, whereas in the effluents the concentrations varied from 125
      to 360 micrograms L-1.

PMID- 11445946
TI  - Evaluation of dialysis as a technique for the removal of lipids prior to the GC
      determination of ortho- and non-ortho-chlorobiphenyls, using 14C-labelled
      congeners.
AB  - Dialysis was evaluated as a non-destructive clean-up technique to isolate
      chlorobiphenyls (CBs) from fish-oil prior to further analysis. 14C-CBs were used
      to study the transfer processes of the CBs across polyethylene membranes. Single
      step processes using equilibrium dialysis were compared to a dynamic method of
      refluxing solvent. The dynamic method reduced the duration of the separation to 8
      h. The transfer of CBs and the lipids was dependent on temperature and nature of
      the analyte with smaller molecules being dialysed substantially faster than
      larger molecules. An optimised dynamic method was used to compare the dialytic
      clean-up with a traditional method using sulfuric acid-impregnated silica for the
      determination of CBs in a laboratory reference material. Labelled recovery
      standards for each individual congener are recommended in combination with
      dialysis as a method for clean-up.

PMID- 11445947
TI  - Trace level determination of phenols as pentafluorobenzyl derivatives by gas
      chromatography-negative-ion chemical ionization mass spectrometry.
AB  - A method for the trace level determination of 11 phenols as pentafluorobenzyl
      (PFB) derivatives by gas chromatography-mass spectrometry (GC-MS) with negative
      ion chemical ionization (NICI) is described. First, the conditions for the PFB
      derivatisation of phenols were optimized and were found to be reaction
      temperature 80 degrees C and reaction time 5 h. Second, the detection limits
      using selected ion monitoring (SIM) were compared between trimethylsilylated
      (TMS) derivatives in the electron ionization (EI) mode and PFB derivatives in the
      NICI mode. The responses for the PFB derivatives in the NICI mode were 3.3-61
      times higher than those of the TMS derivatives in the EI mode. The instrumental
      detection limits using NICI-SIM ranged from 2.6 to 290 fg. This method was
      applied to the analysis of phenols in river water using solid-phase extraction.
      The recoveries of the phenols from a river water sample spiked with standards at
      100 ng l-1 with 2-chlorophenol, 4-chloro-3-methylphenol and pentachlorophenol and
      at 1000 ng l-1 with phenol, 2,4-dimethylphenol, 2,4-dichlorophenol, 2
      nitrophenol, 2,4,6-trichlorophenol and 4-nitrophenol were 81.2-106.3% (RSD 5.1
      8.0%), except for 2-methyl-4,6-dinitrophenol and 2,4-dinitrophenol, for which the
      recoveries were 5.8 and 4.2%, respectively, because water contained in the
      acetone eluate interfered with the derivatisation of these compounds with two
      electrophilic nitro groups.

PMID- 11445948
TI  - The determination of six taste and odour compounds in water using Ambersorb 572
      and high resolution mass spectrometry.
AB  - A method for the analysis of six taste and odour causing compounds in aqueous
      samples using the granular adsorbent, Ambersorb 572, and gas chromatography-high
      resolution mass spectrometry (GC-HRMS) has been developed. This method for the
      determination of geosmin, 2-methylisoborneol (2-MIB), 2-isopropyl-3
      methoxypyrazine (IPMP), 2-isobutyl-3-methoxypyrazine (IBMP), 2,3,6
      trichloroanisole (236-TCA) and 2,4,6-trichloroanisole (246-TCA) is highly
      productive [up to 40 samples per day + 23 quality control (QC) samples] and
      provides rapid (24-48 h) turnaround times. The analytes are extracted from water
      by the addition of Ambersorb 572 to the sample bottle and rolling for 1 h. The
      adsorbent is isolated by filtration and allowed to air dry for 1 h. The Ambersorb
      572 is transferred to an autosampler vial and the analytes are desorbed into
      dichloromethane. The extract is analysed by GC-HRMS at 7000 resolving power (RP).
      Quantification is performed by isotope dilution and internal standard techniques
      utilizing d3-geosmin, d3-2-MIB, d5-246-TCA and 2-sec-butyl-3-methoxypyrazine (s
      BMP). Method precisions of 3.5-5.8% and accuracies of +/- 5.7-8.9% were obtained.
      Reporting detection limits (RDLs) of 1.0 ng L-1 were obtained for 2-MIB, geosmin,
      IPMP and IBMP, while RDLs of 2.0 ng L-1 were obtained for 236-TCA and 246-TCA.

PMID- 11445949
TI  - A novel sample decomposition technique at atmospheric pressure for the
      determination of Os abundances in iron meteorites using isotope dilution
      inductively coupled plasma-mass spectrometry.
AB  - A safe and reliable analytical technique for the determination of Os abundances
      in ten iron meteorites of various chemical groups was developed using isotope
      dilution inductively coupled plasma-mass spectrometry coupled with a sample
      decomposition technique. A major advantage of the sample decomposition technique
      developed here is that the pressure inside the reaction flask is not increased
      through the decomposition reaction because the flask is a fully opened system,
      obviating the risk of explosion of the glass apparatus. Another advantage is that
      there is no restriction in the sample size being decomposed. In this study, about
      2 g of metallic sample were decomposed safely, and this sample size, > 10 times
      larger than that typically used for the Carius tube technique, allows one to
      obtain more reliable Os data for heterogeneous samples. The metallic samples were
      decomposed in a glass flask purged with Ar. Since the O2 was purged from the
      reaction flask, Os was not oxidised to volatile OsO4, thereby preventing
      significant evaporation loss of Os. The typical recovery of Os throughout the
      sample decomposition and separation processes was > 80%, and the total Os blank
      through the decomposition of a 1 g amount of sample was less than 20 pg. Os
      abundances were determined by means of stable isotope dilution mass spectrometry
      using a 190Os-enriched isotopic tracer. Except for Sikhote-Alin, the measured Os
      abundances in almost all the iron meteorites exhibited a good agreement with the
      previously published Os abundance data, within the analytical uncertainty
      achieved in this study (2-5%). For the Sikhote-Alin meteorite, on the basis of a
      better correlation between Os and Ir abundances, we believe that our Os abundance
      data should be more reliable. The Os abundance data obtained in this work clearly
      demonstrated the suitability of the newly developed sample decomposition
      procedure for low level Os determinations.

PMID- 11445950
TI  - Dialysis cells for controlled DNA: drug binding studies.
AB  - An efficient small volume accurate dialysis system has been designed, built and
      tested for proflavine binding to DNA based upon the side by side design used in
      the Franz diffusion cell. In a typical experiment 3 cm3 of DNA solution is added
      to one side and 3 cm3 of ligand to the other with a dialysis membrane between the
      two sides of 1 cm in diameter, thereby minimizing the area of dialysis membrane
      that the solutions are in contact with.

PMID- 11445951
TI  - Robotic enzyme amplification: a comparison of some kinetic properties of bovine
      liver, Candida utilis and Proteus sp. glutamic dehydrogenases.
AB  - NADP(H)-specific Bakers yeast glucose 6-phosphate dehydrogenase (BYG6PDH) was
      paired, in turn, with each of three different source glutamate dehydrogenases
      (GDHs): NAD(P)-specific bovine liver (BLGDH), NADP-specific Candida utilis
      (CUGDH) and NADP-specific Proteus sp. (PSGDH) to constitute three enzyme cycling
      systems; (i) BYG6PDH/BLGDH; (ii) BYG6PDH/CUGDH; and (iii) BYG6PDH/PSGDH. When
      incorporated into an enzymatic cycling/amplification system for NAD kinase and
      run on a centrifugal fast analyzer (CFA), the microbial source enzyme CUGDH gave
      rise to a seven-fold greater amplification rate [21.5 x 10(3) cycles-1 (cph)]
      relative to that realized (3 x 10(3) cph) using the BYG6PDH/BLGDH cycling pair
      previously reported. Either of these cycling systems can be used as a flexible
      and general-purpose module for robotic amplification and data collection of
      NADP(H) linked enzymes as a user's requirements dictate. Although the
      BYG6PDH/PSGDH cycling pair produced a respectable cycling rate (14.4 x 10(3)
      cph), for reasons discussed the PSGDH enzyme was not considered a suitable
      replacement for BLGDH in an NADP(H) cycling system.

PMID- 11445952
TI  - Detection of ferricyanide as a probe for the effect of hematocrit in whole blood
      biosensors.
AB  - Measurement of the concentration of an analyte in whole blood can be influenced
      by a range of factors; the red cell content or hematocrit (Hct) of the sample,
      the distribution and rate of movement of analyte between red cells and plasma,
      the amount of protein in solution, the viscosity of the sample and fouling of the
      sensor. The effect of the red cells is the major factor that must be taken into
      account. Using the analyte molality rather than the analyte molarity, the
      theoretical response for a range of analytes which are found in plasma and in the
      red cells can be calculated. For an analyte which is found in plasma alone, the
      effect of hematocrit is significant, with a bias of -1% per %Hct; if the analyte
      can freely and rapidly diffuse between the red cells and plasma, this bias is
      reduced to zero. Using ferrocyanide as a model analyte, the effects of fouling
      and reduced sample viscosity were measured to be -0.2% per %Hct, giving an
      overall bias of -1.2% per %Hct, a level of bias which is not clinically
      acceptable. This bias can be negated by measuring the hematocrit separately and
      incorporating it into the measurement algorithm. Such a correction is essential
      for the correct measurement of the concentration of an analyte in whole blood.

PMID- 11445953
TI  - Flow injection analysis of L-lactate in milk and yoghurt by on-line microdialysis
      and amperometric detection at a disposable biosensor.
AB  - A disposable lactate biosensor able to operate in flow injection analysis is
      described and characterized. The biosensing layer, obtained by glutaraldehyde co
      crosslinking of lactate oxidase with bovine serum albumin, was cast on an
      underlying electropolymerized layer of overoxidized polypyrrole. The resulting
      biosensor was interference-free and showed a K'M value of 2.4 mmol l-1 and a
      maximum current density of 440 microA cm-2. When integrated in a flow injection
      analysis system, a sensitivity of 300 +/- 10 nA mmol-1 l, a linear response up to
      1 mmol l-1 and detection limits in the low micromolar range were obtained. The
      introduction of a microdialysis membrane-based sampler reduced the sensitivity to
      7.9 +/- 0.2 nA mmol-1 l and extended the linear range up to 50 mmol l-1 lactate.
      The anti-interference characteristics of the biosensor permitted lactate
      determination in untreated milk and diluted yoghurt samples.

PMID- 11445954
TI  - Preparation of microporous aluminium anodic oxide film modified Pt nano array
      electrode and application in direct measurement of nitric oxide release from
      myocardial cells.
AB  - A novel method for fabricating a nano array electrode (NAE) by using micropores
      of aluminium anodic film as templates was investigated. To evaluate the NAE,
      cyclic scanning of NAE in Fe(CN)6(3-) solution was performed and a sigmoidal
      shaped voltammogram was obtained. The NAE was designed to measure nitric oxide
      (NO) in vitro and in vivo. Studies showed that it was a sensitive and selective
      NO electrochemical sensor. NO release from myocardial cells was directly measured
      with this NAE and the results were satisfactory.

PMID- 11445955
TI  - Monitoring metal ion contamination onset in hydrofluoric acid using silicon
      diamond and dual silicon sensing electrode assembly.
AB  - Potentiometric detection of trace levels of metallic contamination onset in
      hydrofluoric acid using a silicon-based sensor in conjunction with two non
      contaminating reference electrode systems is presented in this paper. In the
      first case, conductive diamond was used as a non-contaminating reference
      electrode. Cyclic voltammetry and open-circuit potential experiments demonstrated
      the feasibility of using a conductive diamond film electrode as a quasi-reference
      electrode in the HF solution. In the second case, a dual silicon electrode system
      was used with one of the silicon-based electrodes protected with an anion
      permeable membrane behaving as the quasi-reference electrode. The dual silicon
      sensing electrode system possessed an additional operational advantage of being
      unaffected by the solution acidity. Though both sensing configurations were able
      to detect the metal ion contamination onsets at the parts-per-trillion to parts
      per-billion levels, the dual silicon electrode design showed a greater
      compatibility for the on-line detection of metallic impurities in HF etching
      baths commonly used in semiconductor processing.

PMID- 11445956
TI  - Development of an SPME/ATR-IR chemical sensor for detection of phenol type
      compounds in aqueous solutions.
AB  - A new method, based on a combination of solid phase micro-extraction (SPME) and
      attenuated total reflection infrared (ATR-IR) spectroscopy, was developed for the
      detection of phenols in aqueous solutions. Several types of phenols were studied
      including phenols attached to methyl, hydroxyl, chlorine and nitro groups, which
      are environmentally toxic. Because of the polarity of the phenol-type compounds,
      the performance of six polymers in attracting phenols was investigated. Results
      indicated that poly(acrylonitrile-co-butadiene) was the most suitable SPME phase
      among the investigated polymers. To further increase the sensitivity in phenol
      detection, factors, such as the pH effect, salt effect and thickness of the SPME
      phase, were investigated. Results indicated that pH values affected the neutral
      form percentage of the analytes strongly and, hence, affected the detected
      signals. Due to the acid nature of phenols, phenol detection occurs best in
      solutions with a low pH value. A two- to three-fold increase in signals was
      observed after the addition of salt into the solution. The results on the
      examination of standard curve linearity indicated that the regression
      coefficients (R2) were higher than 0.996 for four types of phenols. The obtained
      detection limits for phenols were lower than 200 micrograms L-1 for most of the
      compounds.

PMID- 11445957
TI  - Determination of horseradish peroxidase and a peroxidase-like iron porphyrin at a
      Nafion-modified electrode.
AB  - A catalytic coupling reaction between 4-amino antipyrine and a N,N-disubstituted
      aniline derivative has been exploited in the indirect electrochemical detection
      of horseradish peroxidase (HRP) and of a biomimetic catalyst, the iron(III)
      sulfonated tetraphenyl porphyrin. In the presence of hydrogen peroxide and one of
      the two catalysts a cationic electroactive quinone-iminium dye P+ was formed and
      detected by linear scan voltammetry using a screen-printed electrode coated with
      a Nafion film. Detection limits of 10(-12) M for HRP and 4 x 10(-10) M for the
      iron porphyrin have been achieved. In conclusion the iron porphyrin is considered
      to be a promising alternative to the HRP label in enzyme immunoassays with
      electrochemical detection.

PMID- 11445958
TI  - Determination of molybdenum in steel by adsorptive stripping voltammetry in a
      homogeneous ternary solvent system.
AB  - A new alternative approach for the determination of molybdenum in steel is
      proposed, using adsorptive stripping voltammetry (AdSV). The determinations are
      performed in a homogeneous ternary solvent system (HTSS) composed of N,N
      dimethylformamide, ethanol and water, with alpha-benzoinoxime (alpha BO) as the
      complexing agent and a sodium acetate-acetic acid buffer as the support
      electrolyte. The HTSS composition was optimized by mixture design modelling. The
      AdSV measurements were performed in the differential pulse mode using an
      accumulation potential of -1050 mV. Under these optimized experimental
      conditions, the Mo(VI)-alpha BO reduction current peak potential is observed at
      potentials near -1250 mV, much lower than those usually reported, and the
      calibration plot follows the polynomial equation I = 0.359 + 0.265 [CMo(VI)] -
      0.015 [CMo(IV)]2 (r2 = 0.997), for Mo concentrations up to 10.0 micrograms L-1.
      There is a linear range in this calibration plot for Mo(VI) concentrations up to
      0.20 microgram L-1, defined by the equation I = 0.353 + 0.385 [CMo(VI)] (r2 =
      0.980). In both cases, I is the absolute value for the current in microA and
      CMo(VI) is the concentration of Mo in microgram L-1. The detection limit for this
      linear concentration range was estimated as 20 pg L-1. A RSD of 0.43% is
      associated with the signals at a Mo(VI) level of 0.72 microgram L-1. From the
      common method-interfering species tested, only iron at Fe/Mo(VI) ratios above 500
      and vanadium and tungsten at M/Mo(VI) ratios above 100 appear to affect the
      analytical response significantly. Phosphorous may also reduce the analytical
      signal at P/Mo(VI) ratios above 100, due to the formation of the competitive P-Mo
      complex. The suggested routine procedure was tested by analyzing four stainless
      steel samples and the results compared well with the ICP-AES measurements. The
      higher sensitivity of this method permits direct determination of Mo(VI) in
      steels, eliminating the need of analyte concentration or separation steps in the
      sample processing procedure.

PMID- 11445959
TI  - Monoparameter sensors for the determination of the antioxidants butylated
      hydroxyanisole and n-propyl gallate in foods and cosmetics by flow injection
      spectrophotometry.
AB  - A flow-through optosensor with solid phase UV spectroscopic detection is proposed
      for the direct determination of single antioxidants, namely butylated
      hydroxyanisole (BHA) and n-propyl gallate (n-PG), without previous
      derivatization. The methods are based on the transient retention behaviour of
      these compounds in a flow-through cell packed with C-18 silica using ethanol
      water mixtures as a carrier, and on the intrinsic absorbance monitored at 290 and
      283 nm, respectively. After recording the analytical signal, the antioxidants
      were easily and quickly desorbed from the solid support by the same carrier. For
      BHA, calibration graphs were linear over the range 1.0-300.0 mg L-1 using area as
      the analytical parameter. The relative standard deviation (RSD) was between 0.5
      and 1.6%. For n-PG, calibration graphs were linear over the range 1.0-300.0 mg L
      1 in area and the RSD was between 1.4 and 1.5%. The methods were applied to the
      determination of these antioxidants in several food and cosmetics samples, and
      were validated using the standard additions method and an HPLC reference method.

PMID- 11445960
TI  - A robust multi-syringe system for process flow analysis. Part 3. Time based
      injection applied to the spectrophotometric determination of nickel(II) and iron
      speciation.
AB  - A new software-controlled time-based system for sample or reagent introduction in
      process flow injection analysis was developed. By using a multi-syringe burette
      coupled with one multi-port selection valve, the time-based injection of precise
      known volumes was accomplished. Characteristics and performance of the injection
      system were studied by injecting an indicator in a buffered carrier. Two multi
      syringe time-based injection (MS-TBI) systems were implemented: first, the
      injection of a sample in a multiple-channel manifold where the sample would
      sequentially merge and react with different reagents, and second, the sequential
      injection of several solutions (sample and reagents) into a particular flowing
      stream. The first system was applied to the spectrophotometric determination of
      nickel(II) in diluted samples from the acidic nickel ore leaching process, by
      using ammonium citrate as carrier, a saturated solution of iodine as oxidizing
      agent and alkaline dimethylglyoxime as chromogenic reagent. The sampling
      frequency attained was 57 h-1. Determinations on process samples compared well at
      the 95% confidence level with the reference values obtained by ICP-OES. The
      second time-based injection system was applied to the speciation of iron. Total
      iron and iron(II) concentrations were separately and sequentially determined
      using 1,10-phenanthroline in acetic buffer medium as reagent. The developed
      manifold allowed the optional use of two different carrier solutions, containing
      or not containing ascorbic acid, for performing the separate determinations.
      Also, in the sequential procedure, plugs of reducing carrier were alternatively
      intercalated before the sample injections used for total iron determinations.
      Sampling frequencies of 68 injections per hour were routinely used. Accuracy was
      assessed by analyzing synthetic known mixtures of Fe(III) and Fe(II) standard
      solutions. Recoveries of 98-100.5% with a maximum relative standard deviation of
      3.6% were found. Results obtained for various samples of fertilizers agreed well
      with those attained by the standard batch procedure.

PMID- 11445961
TI  - Analysis of luminescence spectra of leucite (KAISiO4).
AB  - High-sensitivity radioluminescence (RL) and thermoluminescence (TL) measurements
      were carried out on samples of natural leucite (with 2.95% of Na2O) from Campania
      Vessa (Italy). Samples were annealed to modify the charge compensation through
      alkali metal self-diffusion and to produce luminescence centres. High-temperature
      powder diffraction, scanning electron microscopy and chemical analyses were
      performed to monitor the tetragonal-cubic phase transitions and the thermal
      drainage of alkali metal ions from the aluminosilicate lattice. The emission
      spectral bands of leucite (300, 380, 430, 480, 560 and 680 nm) match those of
      other Na/K-aluminosilicates (alkali metal feldspars) and could be attributed to
      similar defects. TL glow curves of increasingly pre-irradiated natural leucite
      (range 0-20 Gy) showed no changes above 300 degrees C, whereas some changes were
      observed with annealed samples (1000 degrees C for 12 h). This temperature is the
      starting point of Na self-diffusion within the aluminosilicate lattices. The
      areas of the TL glow curves of both natural and annealed beta-irradiated leucites
      can be fitted with a linear function with high correlation. These results are in
      agreement with high alkali metal loss (K2O approximately 12% and Na2O
      approximately 18%) during thermal pre-treatment, high cell volume expansion (from
      2350 to 2500 A) and the cubic la3d reversible tetragonal I4l/a phase transition.
      This promotes the egress of alkali metal ions and the production of [AlO4/M+]o,
      [AlO4/H+]o and [AlO4]o luminescence centres.

PMID- 11445962
TI  - Determination of naproxen in pharmaceutical preparations by room-temperature
      phosphorescence. A comparative study of several organized media.
AB  - Different methods for the determination of naproxen by room-temperature
      phosphorescence (RTP) using organized media such as cyclodextrins (beta-CD and
      gamma-CD) and micelles (Triton X-100 and sodium dodecyl sulfate) are reported.
      The inclusion complexes formed between both beta- and gamma-cyclodextrins and
      naproxen were previously investigated at both acid and basic pH by
      spectrofluorimetry. In both cases, 1:1 guest-host stoichiometries were
      established and the corresponding association constants were calculated.
      Different systems were examined with the purpose of obtaining phosphorescent
      emission from naproxen solutions, and the best signals were obtained when
      naproxen was in the presence of beta-CD-cyclohexane-Tl(I), gamma-CD-1,3
      dibromopropane, Triton X-100-Tl(I) and SDS-Tl(I), respectively. In all cases,
      sodium sulfite was used as deoxygenator. The use of an inorganic compound
      (thallium nitrate) as a heavy-atom source in a cyclodextrin system represents a
      novel finding. Surface response optimization approaches were carried out to
      optimize the chemical variables which have an influence on the RTP emission of
      naproxen. Based on the results obtained, univariate RTP calibration methods for
      the determination of the analyte in pharmaceutical preparations were
      satisfactorily developed. In one case, the standard additions method was applied
      to a mixture of naproxen and the antibiotic tetracycline.

PMID- 11445963
TI  - A direct sensitized fluorimetric determination of 5,10,15,20-tetra(m
      hydroxyphenyl)chlorin [m-THPC (Foscan)] in human plasma using a cyclodextrin
      inclusion complex.
AB  - The 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) (Foscan) is a
      photosensitizer used in the photodynamic therapy (PDT) of cancers which is
      currently under clinical trial. The formation of a m-THPC inclusion complex with
      dimethyl-beta-cyclodextrin (Me-beta-CD) in solution was demonstrated on the basis
      of circular dichroism experiments. A 1:2 complex stoichiometry was found and an
      inclusion constant beta 2 = 2.8(+/- 0.4) x 10(10) M-2 was determined. The
      formation of such a complex was shown to enhance the m-THPC fluorescence
      intensity. It could be exploited to improve the sensitivity of the direct m-THPC
      detection in human plasma. Optimization of the operating conditions shows that
      the best results were obtained by the addition of 100 microL of a concentrated Me
      beta-CD solution (3.2 x 10(-2) M) to 1 mL plasma samples. Compared to the
      standard conditions, a 90% increase in sensitivity was obtained. The proposed
      analytical method which showed a linear response function [0-300 ng mL-1 (440
      pM)] and a low limit of detection [1.5 ng mL-1 (2 pM) (S/N = 3)] appears,
      especially due to the absence of metabolism, a simple and specific method
      suitable for pharmacokinetics studies in patients.

PMID- 11445964
TI  - Fe(II)-EDTA chelate-induced aromatic hydroxylation of terephthalate as a new
      method for the evaluation of hydroxyl radical-scavenging ability.
AB  - The investigation of Fe(II)-EDTA chelate-induced aromatic hydroxylation of
      terephthalate in pH 7.4 phosphate buffer solution and a new method for the
      evaluation of hydroxyl radical-scavenging ability are reported. The method is
      based on attack of the hydroxyl radical on the terephthalate to produce highly
      fluorescent 2-hydroxyterephthalate, which is detected fluorimetrically. The
      formation of hydroxyl radical is believed to be the result of the reduction of
      molecular oxygen by Fe(II)-EDTA to form superoxide radical, which in turn
      dismutates to hydrogen peroxide, and then Fe(II)-EDTA catalyzes the decomposition
      of hydrogen peroxide to produce hydroxyl radical. The mechanism of the generation
      of hydroxyl radical in the proposed system was confirmed. This study established
      a simple and inexpensive method for the evaluation of the scavenging ability of
      some compounds on hydroxyl radicals.

PMID- 11445965
TI  - Field sample preconcentration of copper in sea water using chelating minicolumns
      subsequently incorporated on a flow-injection-flame atomic absorption
      spectrometry system.
AB  - A field flow preconcentration system for copper determination in seawater is
      described. Seawater samples are collected and preconcentrated in situ by passing
      them using a peristaltic pump through a minicolumn packed with Amberlite XAD-4
      impregnated with the complexing agent 1-(2-pyridylazo)-2-naphthol. Thus, copper
      is preconcentrated without the interference of the saline matrix. Once in the
      laboratory, the minicolumns loaded with copper are incorporated on a flow
      injection system and eluted with a small volume of a 20% (v/v) ethanolic solution
      of 0.5 mol L-1 hydrochloric acid into the nebuliser-burner system of a flame
      atomic absorption spectrometer. The analytical figures of merit for the
      determination of copper are as follows: detection limit (3s), 0.06 microgram L-1;
      precision (RSD), 1.2% for 2 micrograms L-1; enrichment factor, 30 (using 25 mL of
      sample and 83 microL of eluent). Analysis of certified reference materials (SLEW
      3 and NASS-5) showed good agreement with the certified value. This procedure was
      applied to the determination of copper in seawater samples from Galicia (Spain).

PMID- 11445966
TI  - Determination of fat in leather by the use of supercritical fluid extraction
      combined with on-line piezoelectric detection.
AB  - Leather samples were prepared and characterized as 'in house' matrix standards
      for the determination of fat. The Soxhlet standard method was used to establish
      the reference fat content in every standard sample. Sample homogeneity and
      stability were examined under specific storing conditions. The materials were
      subsequently used as matrix standards for the determination of fat in leather
      samples, using supercritical fluid extraction (SFE) with on-line piezoelectric
      detection. Real samples were weighed in the extraction SFE thimble, previously
      loaded with 1 g of diatomaceous earth. A temperature of 45 degrees C and a CO2
      fluid density of 0.85 g ml-1 were used for extraction. The linear calibration
      range thus achieved was 0.001-0.040% m/m total fat (related to the weight of the
      leather) and the relative standard deviation +/- 3% (n = 11; P = 0.05). The
      results were compared with those obtained with the Soxhlet method and no
      significant differences were found.

PMID- 11445967
TI  - Uncertainty in sample mass for small numbers of particles from granular
      materials.
AB  - The standard deviation of sample mass was quantitatively related to the number of
      particles in the sample, individual particle masses and the fractions of the
      numbers of different types of particles in the mixture. The theory was verified
      by sampling of cereal grain mixtures with a spinning riffler and Monte Carlo
      computer simulation. The theory is applicable to random sampling of well-mixed
      populations containing two or more types of particles.

PMID- 11445968
TI  - Uncertainty in analyte mass for samples containing small numbers of particles.
AB  - A sampling equation was derived that relates the standard deviation in analyte
      mass to the number of particles in the sample, the fractions of the different
      types of particles in the mixture and the masses and analyte concentrations of
      the individual particles. The equation, which is applicable to samples containing
      any number of particles, was verified by sampling and analysis of two cereal
      grain mixtures for manganese, potassium, chlorine and magnesium, and by Monte
      Carlo computer simulation. Comparison of the sampling precision of analyte mass
      with the analytical measurement precision was also studied, and it was shown that
      use of the equation allows the calculation of the minimum number of particles
      required to hold the sampling relative standard deviation to that of the
      analytical measurement.

PMID- 11445969
TI  - Evaluation of analytical instrumentation. Part XV. Instrumentation for gas
      chromatography-ion-trap mass spectrometry.
AB  - The Analytical Methods Committee has received and approved the following report
      from the Instrument Criteria Sub-Committee.

PMID- 11445970
TI  - Inorganic biological analysis by capillary electrophoresis.

PMID- 11445972
TI  - [Surgical education in 2001].

PMID- 11445971
TI  - [Future specialists].

PMID- 11445973
TI  - [Changes in medical education: why and how].

PMID- 11445974
TI  - [To change medical education].

PMID- 11445975
TI  - [Renewal of medical education. Any difference?].

PMID- 11445976
TI  - [Medical education at the University of Aarhus. Status and growth].

PMID- 11445977
TI  - [Examples of student-activating teaching programs in medial education].

PMID- 11445978
TI  - [Problem-based learning in medical education. Experiences from a department of
      gynecology].
AB  - INTRODUCTION: Problem-based learning (PBL) is an educational method based on a
      clinical problem, where students define their learning objectives, research these
      objectives, and report back. The aim of the present study was to compare PBL with
      other learning methods during a pregraduate clinical course. METHODS: PBL was
      applied to six groups of students (n = 35) during a pregraduate clinical course
      in obstetrics and gynaecology and compared with other learning methods, such as
      traditional lectures, participation in the clinical work of the department, and a
      training course in communication and clinical skills with simulated patients and
      phantoms. The learning methods were scored on a scale from zero to five. RESULTS:
      The educational methods were evaluated differently (p < 0.01). PBL reached a
      score of at least four more often (33/35) than did traditional lectures (25/34),
      p < 0.05. Most of the students enjoyed PBL, although they found it time
      consuming. Twenty-one preferred the mixture of PBL and lectures, whereas 13
      preferred more PBL and one solely preferred lectures. DISCUSSION: The present
      study shows that it is possible to implement PBL sessions in clinical courses and
      the method is positively evaluated by both students and teachers.

PMID- 11445979
TI  - [Questions as evident key to knowledge: teaching medical students evidence-based
      medicine].
AB  - INTRODUCTION: In Denmark, as in other countries, there is an increasing focus on
      evidence-based medicine (EBM) as a necessary tool for using modern sources of
      information, but until now EBM training has not been incorporated in our
      undergraduate curriculum. MATERIAL AND METHODS: This course is given in the ninth
      semester (out of 13) and the subject matter is clinical biochemistry. The course
      consists of seven (one-hour) lectures over three weeks. First, the EBM method is
      introduced, then the students split up into small groups, choose their own
      diagnostic problem, and carry out a structured search. The search leads to the
      choice of a scientific article, which is subsequently presented to and discussed
      by all the students. We asked about their opinion of the course by questionnaire.
      RESULTS: The answers to the questionnaire confirmed that the students have
      improved their ability to read and assess scientific articles and to seek
      information, and it has stimulated them to understand concepts instead of
      memorising details. DISCUSSION: Although the assessment of this course was
      positive, it can no doubt be improved and further developed. In our opinion the
      use of EBM should not be confined to one course. The medical students should be
      introduced to EBM at an early stage, thereby abling them to practice it
      throughout their training.

PMID- 11445980
TI  - [Core curriculum in medical education].

PMID- 11445981
TI  - [Practical clinical skills in medical education 1--undergraduate education. A
      Delphi survey].
AB  - INTRODUCTION: The necessity of defining standards in medical education is
      increasingly recognised. The aim of the present study was to adapt the Delphi
      method in establishing a consensus about competence levels of basic clinical
      skills in the undergraduate medical curriculum. METHOD: We used a Delphi design
      with two postal rounds. An expert panel of 52 physicians was selected on the
      criteria of knowledge and practical engagement in medical education.
      Questionnaires were set up with lists of 213 practical skills based on literature
      studies. Six levels of competence were identified. The task of the panel was to
      select the competence level for each skill. RESULTS: The panel reached a 75%
      level of consensus in 212 of the 213 skills. A core curriculum of basic clinical
      skills in the medical education of Danish undergraduates is proposed. DISCUSSION:
      The Delphi method was found applicable to qualify the process of identifying
      goals in a medical curriculum design.

PMID- 11445982
TI  - [Practical clinical skills in medical education 2--internship. A Delphi survey].
AB  - INTRODUCTION: The aim of the present study was to use the Delphi technique to
      identify standards of quality for the curriculum of basic clinical skills in the
      pre-registration internship. METHOD: The Delphi method was used with a selected
      panel of 52 experts to set a level of competence for 213 practical clinical
      skills in a series of three questionnaires. RESULTS: For the pre-registration
      internship, the panel reached a 75% level of consensus for 80% of the basic
      clinical skills. A total of 47 basic clinical skills were identified (97% level
      of consensus) as core skills that should be mastered by the time of registration.
      DISCUSSION: The study suggests that further investigations should be performed to
      identify a core curriculum of basic clinical skills common to all pre
      registration internists. In addition, a curriculum of electives should be based
      on the special characteristics of each training department.

PMID- 11445983
TI  - [Early clinical exposure--an instant success. The new medical curriculum at the
      University of Aarhus].
AB  - INTRODUCTION: In the new medical curriculum at the University of Aarhus, a third
      term, 20-week course focussing on early patient contact was launched. MATERIAL
      AND METHODS: Nine prototypical and clinically important disease entities each
      formed the basis of one-week courses covering an introductory clinical lecture,
      presentation of "paper" cases, and formalised training of pertinent clinical
      skills. This was integrated with plenaries and group work in physiology
      pertaining to the disease and the patient cases. In addition, seminars were held
      in patient-doctor relationships, and environmental and social medicine.
      Introductory lectures were given on topics, such as medical ethics, taxonomy of
      diseases, the organisation of hospital-based health care. At the end of the term,
      the students resided for eight weeks at county hospitals, which do not
      traditionally participate in pregraduate teaching. Each student followed one
      particular patient, which formed the basis of a written essay. RESULTS: Early
      clinical lectures (87 +/- 8%, mean +/- SD) and use of clinical cases (73 +/- 8%)
      were well received by third term students, and 87% found that the "paper" cases
      facilitated their understanding of physiology. The evaluation of the hospital
      training was very positive (rated excellent or good by > 95%). DISCUSSION: We
      conclude that early introduction to clinical practice is feasible and well
      received by the students.

PMID- 11445984
TI  - [IT in education of health professionals].

PMID- 11445985
TI  - ["And so we'll equally evaluate..." When the education was evaluated].

PMID- 11445986
TI  - [Assessment of competence in clinical education].

PMID- 11445987
TI  - [Changed working plans can improve medical training].
AB  - INTRODUCTION: The quality of clinical medical training in Denmark has been
      closely debated and criticised in recent years. Reorganisation of the daily
      working plans is one of the recommendations for improvement. METHOD: In the
      Department of Gastrointestinal Surgery, we made changes in the daily working
      plans in order to improve supervision and training. These changes included firmer
      attachment of the young residents to specialised medical teams in the department
      and the creation of more supervised working situations. The morning rounds were
      done by all the senior and junior doctors in the team together, which meant that
      the rounds could be completed in half-an-hour and consequently more senior
      doctors were available for supervision during the rest of the day. This was
      adopted by the outpatient clinic, the endoscopy unit, and the operating rooms,
      where activities did not start until after the rounds. RESULTS: The changes led
      to a considerable increase in the number of working situations with supervision.
      Assessment by a questionnaire showed that residents also found significant
      improvements in supervision during all clinical activities. Overall satisfaction
      with the department and working conditions increased. CONCLUSION: Many different
      aspects must be considered if clinical medical training is to improve. One key
      factor is a thorough revision of the daily working plans, so as to establish as
      many supervised teaching situations as possible.

PMID- 11445988
TI  - [The Cusum score. A tool for evaluation of clinical competence].
AB  - INTRODUCTION: The cusum analysis (cummulative summation) is a statistical
      technique used to assess the competence of medical trainees. We wanted to re
      examine the validity of the test as a technique for qualitative assessment of
      competence, as well as a technique for monitoring the level of specialists'
      competence. METHODS: Doctors in two anaesthetic departments were asked to plot
      the cusum as they performed the following procedures: epidural and spinal
      analgesia, insertion of central venous and arterial cannulae. RESULTS: Data were
      collected over a year. Thirty-five doctors were asked to plot the cusum. The
      plots were returned by 75% (9/12) of the first year trainees, 50% (4/8) of the
      second- and third-year trainees, and 20% (1/5) of the four- and five-year
      trainees. From the specialists and consultants on the staff, we received 66%
      (4/6) and 50% (2/4). The correlation, according to the level of competence
      respecting spinal and epidural techniques, is shown in Figures 1 and 2.
      DISCUSSION: We found, that the cusum analysis is a valid and practical technique
      for the qualitative assessment of clinical competence as well as a tool for
      monitoring continuous professional development. The technique can be used in a
      number of settings. With the increasing demand in health care for continuous
      quality assurance, the analysis can be used both in personal professional
      monitoring and in monitoring of performance during training.

PMID- 11445989
TI  - [Simulation-based training in continuing medical education].

PMID- 11445990
TI  - [Virtual reality-computer simulation as a tool for training and evaluating skills
      in laparoscopic surgery].

PMID- 11445991
TI  - [Continuing medical education--why and how].

PMID- 11445992
TI  - [Urologic training and basic surgical training in Queensland, Australia].

PMID- 11445993
TI  - [Teacher among physicians!].

PMID- 11445994
TI  - [Medical education journals].

PMID- 11445995
TI  - [Surgical training one more time!].

PMID- 11445996
TI  - Molecular evolution: first enzymes, gases as substrates and genetic templates.
AB  - A fundamental problem in biology is the self-assembly of the first cells capable
      of growth and division under anoxic conditions on the Earth. Evolution proceeded
      by self-assembling and self-replicating cells that reproduced their own genetic
      information and also changed their genetic code over time. Was it also possible
      that some of the first proteins were catalytic and used gases as substrates and
      also acted as genetic templates? This paper explores the possibility that
      primitive protein enzymes used gases as their substrates, and reverse translation
      may have been a feature in the self-assembly of the first cell(s).

PMID- 11445997
TI  - On Darwin's 'metaphysical notebooks'. I: teleology and the project of a theory.
AB  - Huxley's essay On the Reception of the 'Origin of Species' brings us close to the
      issue of cause and of why- and how-questions in the understanding of the living
      world. The present contribution, which is divided into two parts, reviews the
      problem of Teleology as conceived by Huxley and re-examines Darwin as the author
      who revealed the existence of a 'foundations problem' in the explanation of an
      entire realm of nature, i.e., the problem of explaining such realm in terms of
      its own, specific legality, or iuxta sua propria principia. In the first part the
      enquiry is mainly focused on the secularization of natural history after Paley;
      in the second part it is mainly focused on the desubjectivization of the inquiry
      into natural history after Erasmus Darwin and Lamarck. The second part will be
      published in the next issue of Rivista di Biologia/Biology Forum. In the first
      part below an analysis is made of Notebooks M and N. The author disputes the
      correctness of conceiving them only as the works where Darwin envisages the
      'metaphysical' themes later to become the subject of The Expression of the
      Emotions. He suggests to conceive of them also as the works where Darwin defines
      the terms of the general project of his own, peculiar evolutionary theory. The
      author then outlines the intellectual progress of Darwin from the inosculation to
      the transmutation hypotheses. Darwin's reading of Malthus appears to be
      analytically decisive, because it offers him the vintage point to attack the
      metaphysical and theological citadels on the morphological side. Darwin is thus
      able to re-consider Erasmus' comprehensive zoonomic project, by displacing it,
      however, from the old idea of the scala naturae to the new one of the "coral of
      life", and by emphasising the distinction between "the fittest" and "the best"
      vs. the tradition of Natural Theology.

PMID- 11445998
TI  - Fundaments of plant cybernetics.
AB  - A systemic approach is proposed for analyzing plants' physiological organization
      and cybernesis. To this end, the plant is inspected as a system, starting from
      the integration of crown and root systems, and its impact on a number of basic
      epigenetic events. The approach proves to be axiomatic and facilitates the
      definition of the principles behind the plant's autonomous control of growth and
      reproduction.

PMID- 11445999
TI  - Hormones in mammalian evolution.
AB  - Animals that produced increased levels of prolactin and dehydroepiandrosterone
      (DHEA) survived the period of mass extinctions at the end of the Cretaceous
      period. DHEA increases thermogenesis and supported existence through the extended
      episode of cold and dark. Further increases in DHEA and prolactin produced
      continual physiological and anatomical changes which eventually produced all of
      the characteristics of mammals.

PMID- 11446000
TI  - Proteins, nucleic acids and genetic codes.
AB  - On the basis of the previous article (Morchio and Traverso [1999]), we discuss
      the possible interactions between the first proteic fragments developed in the
      hydrophobic layer made of hydrocarbons, which would have covered the surface of
      the primitive seas, and the nitrogenous bases, particularly the pyrimidinic ones,
      which would have found in such hydrophobic layer favourable conditions to their
      prebiotic synthesis. These interactions would have presumably brought, on the
      basis of the physicochemical laws, at the moment the only ones at work, to the
      linkage of various bases and so to the construction of the first nucleic acid
      chains (most likely RNA). Interestingly enough this result would have been
      obtained by inserting two more bases between those hydrogen bound to the amino
      acids and this might have been the ground for the future "triplets". These
      interactions might have been particularly significant because of two important
      consequences: the birth of a rough genetic code and the starting of interactions
      of the co-operative type between bases and amino acids that would have made the
      growth of both proteic and nucleic acid fragments easier and faster. We conclude
      that the development of the genetic code was neither a "frozen accident" nor an
      occurrence directed by any information flow.

PMID- 11446001
TI  - The living state of matter.
AB  - Progress in biology has been extremely fast in the second half of the twentieth
      century in terms of numbers and quality of data. However less attention has been
      paid to the revision of existing theories on living beings structure and dynamics
      in development and evolution. Within this frame, the discussion on the very
      definition of life is lagging in the sometimes ideological debate between
      mechanistic and holistic views often without serious trials to integrate the
      overwhelming amount of new data into the different theoretical frameworks. The
      aim of this short review is to try to define a series of parameters specific of
      the living state of matter on the basis of existing evidence. The analysis starts
      from mathematical, physical and experimental studies on DNA constraints in
      nucleotide distributions and the interactions with proteins in some basic
      processes of life. The data discussed seem to show that short and long range
      correlations in DNA, particularly significant in non coding regions and
      increasing during evolution may have been fixed because of the need of structural
      landscapes complementarity for DNA-protein recognition and complex dynamics. The
      need for highly efficient and frequent recognition between the molecules has been
      extended to gene expression, protein-protein, protein-ligand complex formation
      and to signal transduction pointing out to the relevance of plasticity on one
      hand, complementarity on the other. Compartmentalisation and individuality are
      then taken as critical conditions favouring such processes in the hierarchical
      networks of all levels, from the cell to organisms, populations, ecosystems, the
      biosphere. Finally the specific meaning in life of useful (correlated) and
      disruptive noise is discussed along with the dynamics of evolutionary change in
      terms of homeorrhetic, plastic maintenance of flexible equilibria continuously
      challenged by internal and external signals.

PMID- 11446002
TI  - A cyclic model for bimodal activation of calcium activated potassium channels in
      radish vacuoles.
AB  - This paper presents the mathematical framework of a cyclic model proposed for
      describing the transition between a fast and a slow mode (fast-slow effect)
      induced by the application of step membrane potentials to ion channels from
      radish vacuoles. A voltage stimulation pulse with frequency in the range of 2 Hz
      or higher increased the activation time (slow mode) of the recorded currents.
      When the frequency of the stimulation pattern was restored to 0.1 Hz the
      activation time decreased twofold (fast mode). This experimental result cannot be
      explained by classical kinetic theory. The model, based on a simple extension of
      the Hodgkin and Huxley chain, describes the whole current experimental data and
      provides hints on the structural conformation of ion channels.

PMID- 11446003
TI  - [Hesitation in connection with the general practice system].

PMID- 11446004
TI  - [Norwegian medical students abroad].

PMID- 11446005
TI  - [The global alcohol-free day, what happened?].

PMID- 11446006
TI  - [Normal pressure hydrocephalus].

PMID- 11446007
TI  - [Norwegian medical students abroad--background, effort and satisfaction].
AB  - BACKGROUND: More than 30% of Norwegian physicians have graduated from medical
      schools outside Norway, and the number of Norwegian students that attend medical
      schools abroad is increasing, particularly in Hungary, Poland and the Czech
      republic. It is of interest to know more about these future Norwegian doctors:
      where they come from, and how they cope with studying abroad. MATERIAL AND
      METHODS: A postal survey was carried out among all 1,198 Norwegian medical
      students that were in the files of the State Education Loan Fund by August 1998.
      There were 756 responses (63%). The questions covered reasons for going abroad,
      academic and non-academic outcome, satisfaction, specialty and job preferences,
      possible motives for career choices, personality traits, smoking status and
      alcohol use. Comparable data were available from previous studies of medical
      students in Norway. RESULTS: The social background of students abroad is similar
      to that of students at home, and their high school grade level is only slightly
      below. The main reasons for studying abroad is that they were not admitted at a
      Norwegian university and have a strong wish of becoming a doctor. Language,
      financial situation, and a number of pragmatic reasons determine which country to
      go to, choice of university is often incidental. Students abroad spend more time
      on their studies than students at home do. They are generally satisfied with the
      academic quality, but satisfaction with how the study is organised is lower in
      Central and Eastern-European countries. INTERPRETATION: Norwegians who are highly
      motivated but excluded from Norwegian universities increasingly attend medical
      schools abroad and are by and large satisfied with the quality of the curriculum.

PMID- 11446008
TI  - [Norwegian medical students abroad--career plans, personality, smoking and
      alcohol use].
AB  - BACKGROUND: More than 30% of Norwegian physicians have graduated from medical
      schools outside Norway, and the number of Norwegian students that attend medical
      schools abroad is increasing, particularly in Hungary, Poland and the Czech
      republic. There is a need to know more about these future Norwegian doctors, what
      their motives and plans are, and how they differ from students at home. MATERIAL
      AND METHODS: A postal survey was carried out among all 1,198 Norwegian medical
      students that were in the files of the State Education Loan Fund by August 1998.
      The questions covered reasons for going abroad, academic and non-academic
      outcome, satisfaction, specialty and job preferences, possible motives for career
      choices, personality characteristics, smoking status and alcohol use. Comparable
      data were available from previous studies of medical students in Norway. RESULTS:
      There were 756 responses (63%). Surgery, internal medicine and paediatrics were
      the most popular specialties. Family medicine and psychiatry seem to be less
      likely specialties for students abroad than for students at home. Traditional
      gender differences, e.g. interest in aiming for a leadership position, were
      present and did not differ from those seen among students in Norway. Students
      abroad were more oriented towards leadership and prestigious specialties, less
      preoccupied with the possibility of making medical mistakes, and less interested
      in medico-policial issues than their counterparts at home. Their personality
      profiles seemed more robust than those of students in Norway. On the other hand,
      they smoked much more frequently and had a higher risk of alcohol-related
      problems. INTERPRETATION: Norwegian medical students abroad do not particularly
      prefer specialties like general practice and psychiatry, where the demand for
      medical manpower is highest. They seem to have quite traditional preferences
      according to gender.

PMID- 11446009
TI  - [Surgical treatment of normal pressure hydrocephalus].
AB  - Normal pressure hydrocephalus (NPH) is an important diagnosis to keep in mind,
      i.e. the possibility that NPH and not a neurodegenerative disease causes the
      patient's symptoms with ataxia, urinary incontinence and dementia. Clinical
      improvement, sometimes a complete reversal of the symptoms, may be seen after a
      simple surgical procedure. This prospective study was performed by testing eight
      consecutively shunted patients with a walking test and a cognitive test battery
      pre- and postoperatively. Improvement 3-4 months after the shunting procedure
      suggests that NPH was present in six of eight patients. Walking ability was
      improved after surgery, also in patients with severe dementia. Severe dementia
      caused by NPH is hardly reversible, though cognitive tests may indicate some
      improvement. However, early surgical treatment of NPH in patients not suffering
      from a dementia according to the Mini Mental Status Test may bring improvement in
      some cognitive functions. Patients with both clinical and radiological signs of
      normal pressure hydrocephalus should be offered a shunting procedure.

PMID- 11446010
TI  - [Resection of malignant tumors involving the anterior cranial fossa].
AB  - BACKGROUND: The craniofacial approach has greatly facilitated resections of
      tumours involving the base of the anterior cranial fossa when compared to either
      the transcranial or transfacial approach alone. MATERIAL AND METHODS: This
      approach was used in 11 patients with malignant tumours localized to the ethmoid
      sinus, orbit and bone or soft tissue of the base of the anterior part of the
      skull. By combining a low frontal or frontolateral craniotomy with resection of
      the facial skull, en bloc resections were accomplished. A frontogaleal periostal
      flap or a muscle flap from the temporal muscle was used to replace resected bone
      and to seal the skull base. RESULTS: There were no peri- or postoperative deaths.
      One patient died due to local recurrence, one patient is alive with residual
      tumour six years after surgery, and one is reoperated due to local recurrence. In
      addition one patient developed recurrence of a previously treated tumour of the
      maxillary sinus. Two patients developed meningitis and one pneumocephalus
      postoperatively. One patient has partial loss of vision and two patients
      underwent dacryocystorhinostomy due to epiphora. INTERPRETATION: The planning and
      execution of this type of surgery requires close interaction in an
      interdisciplinary team, in particular between neurosurgeon and head and neck
      surgeon.

PMID- 11446011
TI  - [Acute osteomyelitis in young children--a diagnostic challenge].
AB  - BACKGROUND: Acute osteomyelitis in young children poses a diagnostic challenge.
      Signs and symptoms are often not well defined and blood tests (SR, CRP etc.) are
      often of limited value. Standard roentgenograms do not preclude the diagnosis.
      MATERIALS AND METHODS: We present eight cases of acute osteomyelitis in children
      under the age of two, seen at the Child Centre, at Ullevaal University Hospital
      during the last year. RESULTS: Scintigraphic interpretation failed to reveal the
      diagnosis in two cases. Magnetic resonance imaging (MRI) was shown to be a more
      reliable method. Only a few biopsies were done. INTERPRETATION: Examination of
      children suspected of suffering from an osteomyelitis should include both a bone
      scintigraphy, MRI, and to the extent possible a needle biopsy.

PMID- 11446012
TI  - [Colorectal cancer--experiences with the use of standardized forms for reporting
      pathologic-anatomic data].
AB  - BACKGROUND: Colorectal cancer is the second most common cancer among both men and
      women in Norway. The quality of the information given in the histopathological
      report is crucial for staging and treatment, and standardised reports are
      recommended. Such standardised schemes for histopathological reporting and
      surgical specimen handling were introduced from 1 July 1996 and 1 January 1998,
      respectively. The present study was undertaken in order to evaluate these schemes
      and to investigate to what extent the procedures complied with international
      recommendations. MATERIAL AND METHODS: An evaluation of all histopathological
      reports from 390 patients operated for colorectal carcinomas and registered at
      the Department of Pathology of the Central Hospital of Rogaland 1 July 1996 to 30
      June 1999. RESULTS: The standardised schemes were used in 184 of 193 cases of
      surgical specimen handling (95%) and in 381 of 390 cases of histopathological
      reporting (98%). The quality of the histopathological reports, was in good
      agreement with international recommendations with respect to most data items.
      However, the average number of 9.0 lymph nodes sampled was below the minimum of
      12 recommended by the International Union Against Cancer. In 29% of the cases,
      less than six lymph nodes were found. INTERPRETATION: Although the standardised
      schemes were used almost uniformly, the schemes did not ensure by themselves that
      all data items were in accordance with international recommendations. The fact
      that too few lymph nodes were sampled, was only detected during the present
      evaluation. Thus, any introduction of standardised schemes should include a
      regular follow-up to ensure that predefined goals are attained.

PMID- 11446013
TI  - [Emergency service in Arendal--a new model of intermunicipal emergency service].
AB  - BACKGROUND: Over the past years there has been increasing debate over the
      organisation of off-hour primary care emergency services. In March 2000 we
      established an emergency room serving 80% of the total population of a Norwegian
      county, Aust-Agder. The most important change introduced was a reduction in house
      calls. Patients from smaller municipalities now have to come in to the emergency
      room; previously many consultations were made in the patients' own homes. This
      organisational model has now been evaluated to see if it made patients less
      satisfied and whether it was less expensive to run. MATERIAL AND METHODS: 100
      patients were interviewed by questionnaire in order to see if there were changes
      in their satisfaction with the emergency services provided. Costs were studied by
      collecting data from the social security service and from the participating
      municipalities before (1999) and after (2000) the reorganisation. RESULTS: The
      overall impression is that patients have not expressed any dissatisfaction with
      the new organisational model and that it has cut expenses. We found that the
      social security service had cost savings of 31% for doctors on call, while the
      municipalities had an increase in expenditure of 17%. INTERPRETATION: It is
      possible to establish larger off-hour primary care emergency services without
      greater inconvenience to the patients. The new model is beneficial for doctors
      and saves costs for society, though the social security service's savings are
      somewhat offset by increased expenses on the part of the municipalities.

PMID- 11446014
TI  - [Local groups as a tool for quality assurance of community health services].
AB  - BACKGROUND: The aim of this study was to assess the use of local
      interprofessional or audit groups as a tool of quality enhancement. MATERIAL AND
      METHODS: Fifty-six doctors, physiotherapists and nurses attended nine local
      interprofessional groups. The aim was to improve the quality of each
      professional's practice and to improve communication between the professions.
      RESULTS: The groups had a total of 62 meetings with each professional attending
      on average 5.7 meetings. All groups initiated quality enhancement projects.
      Initially the groups were very active and showed great initiative, but there were
      few final results. However, many groups reported improved communication and
      cooperation between the participating professionals. INTERPRETATION: The
      experience from this project may be summarised as follows: The professionals
      within one and the same group should have more or less the same background and
      specialty. We recommend caution with organising interprofessional groups unless
      their participants work in the same practice. Interprofessional groups should
      spend adequate time for the members to get to know each other, and they should be
      guided by an experienced leader.

PMID- 11446015
TI  - [Smoking and coronary heart disease].
AB  - BACKGROUND: Smoking increases the risk of developing coronary heart disease in
      men and women. MATERIALS AND METHODS: Several epidemiological studies have
      demonstrated an almost linear relationship between smoking and coronary heart
      mortality and morbidity, the risk being more than twofold and most pronounced in
      younger individuals. RESULTS: Smokers are younger than nonsmokers when they
      suffer their first myocardial infarction, more of them are males, and they
      experience more frequently posterior infarcts. They are likely to develop right
      coronary occlusions, the lesions being rather thrombogenic than atherosclerotic.
      This phenomenon may partly be related to the specific flow pattern in the right
      coronary artery. Passive smoking is harmful. Quitting smoking in patients and in
      healthy individuals reduces the risk markedly within a short period of time.
      INTERPRETATION: Smoking causes vasoconstriction of coronary arteries, and
      endothelial function as well as fibrinolysis is impaired while platelets are
      activated. A human ex-vivo experimental model has shown that the thrombus volume
      was increased twofold in blood from smokers at shear forces that are found in
      moderately stenosed coronary arteries. In addition, smokers are insulin-resistant
      and at increased risk of developing diabetes mellitus.

PMID- 11446016
TI  - [Neonatal hypoglycemia].
AB  - BACKGROUND: The definition, significance, and management of neonatal
      hypoglycaemia and the establishment of a safe, lower limit for blood glucose
      concentration in the newborn is still a matter of controversy. METHODS: A review
      of the literature on neonatal hypoglycaemia is presented and guidelines for
      prevention and treatment discussed. RESULTS: Healthy, full-term, appropriate for
      gestational age infants are thought to have a better tolerance for low blood
      glucose values during the first days of life than later in life. The infant's
      brain is capable of utilizing alternative energy substrates, such as ketone
      bodies and lactate. Intracerebral glycogen stores in the astrocytes and increased
      cerebral blood flow in response to hypoglycaemia maintain a sufficient substrate
      delivery. Infants at risk of developing neurological impairment following
      hypoglycaemia have a reduced capacity for mobilizing glucose from the
      glycogenolysis or gluconeogenesis and for utilizing alternative substrates for
      energy. INTERPRETATION: There are no established lower limits defining neonatal
      hypoglycaemia of the healthy infant, but operational guidelines exist for
      prevention and intervention in infants at risk, for whom the blood glucose
      concentration should be maintained > or = 2.6 mmol/l. Very few healthy,
      breastfed, term infants have blood glucose levels < 2 mmol/l. It is suggested
      that values down to 1.7 mmol/l should be accepted as normal during the first day
      of life. Parenteral glucose should be administered to all infants with blood
      glucose levels < 1.4 mmol/l. The main goal is to prevent neonatal hypoglycaemia.
      Early and exclusive breastfeeding and the maintenance of normal body temperature
      are usually sufficient preventive measures in healthy infants.

PMID- 11446017
TI  - [Aagenaes syndrome--lymphedema and intrahepatic cholestasis].
AB  - The combination of neonatal intrahepatic cholestasis and lymphoedema in feet and
      legs is a specific syndrome named after the Norwegian paediatrician Oystein
      Aagenaes, who described the syndrome in 1968. The condition is autosomal
      recessively inherited and the gene is located to 15q, but not yet identified. The
      condition is particularly frequent in the southern most part of Norway and the
      gene frequency is estimated to be about 3%. The development of small lymphoid
      vessels is probably deficient around the small biliary tracts and in general.
      Aagenaes' syndrome is found in patients from other parts of Europe and the US,
      but more than half of the cases are of Norwegian origin.

PMID- 11446018
TI  - [Do thiazide diuretics cause diabetes?].

PMID- 11446019
TI  - [Communication with cancer patients--the matter of course can easily be
      forgotten].

PMID- 11446020
TI  - [Life in English general practice].

PMID- 11446021
TI  - [When does stored blood become old?].

PMID- 11446022
TI  - [Is Ritalin prescribed insufficiently to hyperactive children in Nordland?].

PMID- 11446023
TI  - [What's wrong with asthma clinics?].

PMID- 11446024
TI  - [Temporomandibular-whiplash injuries, the Helsetilsynet gone astray].

PMID- 11446025
TI  - [Acupuncture in acute lumbago].

PMID- 11446026
TI  - [Decreased platelet aggregation during angiotensin-converting enzyme inhibitor
      therapy. Results of a pilot study].
AB  - BACKGROUND AND OBJECTIVE: Plaque rupture and subsequent thrombosis are key events
      in the complication and progression of atherosclerotic disease. Recently, the
      HOPE study showed a significant decrease in cardiovascular complications with the
      angiotensin converting enzyme (ACE) inhibitor (ramipril). To assess the
      therapeutic potential of this drug class, the present study evaluates the
      coagulative activity in cardiovascular patients with ACE inhibitors and compares
      these data with those of untreated patients and with those of patients taking
      aspirin, resp. METHODS: Blood samples from 204 patients with coronary heart
      disease and/or arterial hypertension were analyzed by whole-blood lumi
      aggregometry. Platelet aggregation was determined by the increase in impedance
      across paired electrodes in response to the stimulatory agents collagen and ADP,
      respectively. The data were correlated with the presence or absence of ACE
      inhibitor and/or aspirin medication. Analogously, the coagulative potential of
      beta-blockers, calcium antagonists, CSE-inhibitors and nitrates were studied.
      RESULTS: As the central finding, study participants treated with ACE inhibitors
      showed a decreased platelet aggregation compared to untreated control patients,
      indicated by a significantly reduced increase in impedance. Platelet aggregation
      induced by collagen decreased by 18% (p = 0.025), that induced by ADP by 39% (p =
      0.039). With aspirin medication, the collagen-induced decrease amounted to 20% (p
      = 0.020); no significant effect was seen by ADP stimulation. With combined intake
      of ACE inhibitors and aspirin, collagen-induced platelet aggregation was found
      markedly reduced. Platelet aggregation decreased by 26% (p = 0.003). Beta
      blockers, calcium antagonists, CSE inhibitors and nitrates did not reveal a
      significant influence on platelet aggregation. CONCLUSIONS: ACE inhibition
      decreases platelet aggregation, as detected and quantified by ex vivo whole-blood
      aggregometry. Beyond known effects of this drug class, in particular on
      endothelium and fibrinolysis, antithrombotic effects may explain the positive
      influence on major clinical cardiovascular events.

PMID- 11446027
TI  - [The practice of medical postmortem examination].
AB  - BACKGROUND AND OBJECTIVE: The quality of the external examination of corpses has
      repeatedly been criticized. This study provides information on the performance of
      the external examination of bodies in practice which is necessary for improving
      the quality of the examination. METHODS: 1000 randomly selected medical
      practitioners from the "Arztekammer Westfalen-Lippe" were sent a questionnaire
      concerning personal data, the performance of the external examination of bodies
      and possible influencing of the decision on the manner of death (i.e. natural,
      unnatural or uncertain) by a third person. In addition reports of four typical
      cases were presented and a classification of the manner of death was requested.
      RESULTS: The return rate of the questionnaires was almost 30%, 289 questionnaires
      were evaluated. Although most doctors stated that the external examination took
      them 20 to 30 minutes, only 25% undressed the body completely. Almost 50% of the
      doctors had been influenced by a third person in the decision on the manner of
      death at least once, most often by the police. The four short cases were
      incomprehensibly often classified as "natural death", especially by internists.
      CONCLUSIONS: Signs of an unnatural cause of death will only be detected by chance
      if the body is only briefly examined and not undressed completely. If such signs
      are absent the manner of death should be classified as "uncertain" in unclarified
      or doubtful cases, even against attempted influencing by third persons. In order
      to avoid conflicts of interests it would be desirable if only specialized medical
      practitioners would perform the external examination of corpses.

PMID- 11446028
TI  - [Multiple paradoxical emboli in patent foramen ovale].
AB  - HISTORY AND CLINICAL FINDINGS: A 38-year-old man was admitted because of angina
      pectoris with concomitant dyspnoea. Three months previously he had suffered an
      ischaemic stroke of the right middle cerebral artery and was treated in a
      neurological department. At that time, no aetiologic diagnosis was possible.
      There was no history of other diseases. Pulse rate was 100 beats per minute with
      a blood pressure of 140/60 mm Hg. The left calf had a 4 cm greater circumference
      without any symptoms. The rest of the physical examination in the markedly
      overweight patient was normal. INVESTIGATIONS: The ECG showed sinus rhythm and
      negative T-waves in leads V1-V4 and a slightly elevated ST-segments in II, III
      and aVF. An acute coronary thrombosis was ruled out by left heart catheter-angio.
      DIAGNOSIS, TREATMENT AND COURSE: Within the following hours, embolic occlusion of
      the left popliteal artery developed and was treated with a Fogarty catheter. On
      the first postoperative day, the patient complained about mild dysaesthesia of
      his right arm. Duplex sonography showed a floating thrombus in the left carotid
      bifurcation. The thrombus was removed surgically. Later a pulmonary embolism due
      to deep vein thrombosis in the left thigh and calf was found. Transoesophageal
      echocardiography performed in another hospital previously was repeated and a
      patent foramen ovale (PFO) with a middle-sized shunt was found. The patent
      foramen ovale was closed percutaneously by implanting a Cardioseal-Starflex
      occluder. There was neither a complication nor a residual shunt. Neurological
      symptoms disappeared completely within the next few months. The patient has now
      been free from new neurological events for 11 months. CONCLUSION: In patients
      with PFO, paradoxical embolism remains a challenging diagnosis that can be made
      highly probable by documentation of venous thromboses, pulmonary embolism,
      missing evidence of atherosclerosis in the vessels of the embolized organ and
      exclusion of other cardiovascular sources of emboli and prothrombotic coagulation
      disorders. Interventional closure of a patent foramen ovale appears to be the
      treatment of choice in proven paradoxical embolism.

PMID- 11446029
TI  - [Successful use of a button system in "buried bumper" syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 65-year-old patient had a fracture of the skull
      with resulting swallowing disorder and underwent percutaneous endoscopic
      gastrostomy (PEG) 9 months previously. A specific home care and maintenance of
      the PEG was not provided. The patient was referred to our hospital because of
      haematemesis on the suspicion of upper gastrointestinal bleeding. He was in a
      generally reduced condition with the clinical signs of anaemia and with a
      positive shock index. INVESTIGATIONS: The laboratory tests revealed an anaemia.
      The gastroscopy showed an active bleeding ulcer under the migrated internal
      bumper of the PEG (buried bumper syndrome). The bleeding activity was classified
      as Forrest lb. In addition, the chest X-ray and the bronchoscopy showed bilateral
      pneumonia. DIAGNOSIS, TREATMENT AND COURSE: Summarizing the diagnoses there was
      an active bleeding ulcer in the sense of a buried bumper syndrome in combination
      with bilateral pneumonia caused by aspiration. After releasing the bumper the
      bleeding was stopped by local injection therapy. As additional treatment of the
      lesion it was aimed to lower pressure on the affected mucosal area. This was
      achieved by the use of a button gastrostomy with a liquid-filled retention
      balloon that was placed through the preexisting stoma. The pneumonia was treated
      with antibiotics. Follow-up gastroscopies revealed good healing of the ulcer and
      the patient was discharged. CONCLUSIONS: The complication of a buried bumper
      syndrome with ulcer bleeding can effectively be treated by the use of a button
      gastrostomy. Treatment is based on sufficient pressure relief in the affected
      mucosa area. Advantages can be seen in the maintenance of the stoma and in the
      opportunity for an early continuation of enteral feeding.

PMID- 11446030
TI  - [Current diagnosis of Sneddon syndrome].

PMID- 11446031
TI  - [Malnutrition in the hospital--prevalence, clinical consequences, economic
      relevance].

PMID- 11446032
TI  - [Chronic diarrhea following cholecystectomy].

PMID- 11446033
TI  - [Classification of diabetes mellitus].

PMID- 11446034
TI  - [How do clever students become clever physicians?].

PMID- 11446035
TI  - [Managers of fragments].

PMID- 11446036
TI  - [National and international work against doping].

PMID- 11446037
TI  - [Epidural analgesia in labor].

PMID- 11446038
TI  - [Cerebral paresis].

PMID- 11446039
TI  - [Medical problems and needs of follow-up in a group of children with mild
      cerebral palsy].
AB  - BACKGROUND: There is no specialized health service for routine follow-up for
      ambulatory children with cerebral palsy in Rogaland county. Our aim was to
      investigate the kind of medical problems these children had and whether these
      problems were discovered by the health services. MATERIAL AND METHODS: 37
      children with cerebral palsy born 1987-1992 were investigated. They were all
      independent walkers without mental retardation at the time of selection. The
      majority had spastic hemiplegia or spastic diplegia. Their parents were
      interviewed and the children underwent a neurological examination. RESULTS:
      Orthopedic problems such as scoliosis, hip abnormalities, tight tendons and
      muscles, and leg length discrepancy were not discovered by the local health
      service. The children had a high incidence of epilepsy, visual disorders and
      minor speech problems. Minor learning difficulties were frequent. INTERPRETATION:
      Children with mild cerebral palsy have specific problems and need the attention
      of neuropediatricians in order to establish the primary and secondary problems
      involved.

PMID- 11446040
TI  - [Feeding problems and growth disorders among children with cerebral palsy in
      south and north Trondelag].
AB  - BACKGROUND: Growth retardation is common in children with cerebral palsy. This
      may in part be due to the cerebral injury, but insufficient nutrition may also
      play a role. The aim of the present study was to estimate the prevalence of
      feeding problems, growth retardation, underweight and overweight in children with
      cerebral palsy. MATERIAL AND METHODS: Population-based study of children with
      cerebral palsy in two Norwegian counties. Information was obtained both from
      parents and from medical records. 154 children born between 1 January 1982 and 31
      December 1996 were included in the study. RESULTS: 30% of the children had height
      below the 2.5th centile, 10% had weight for height below the 2.5th centile, and
      7% were obese (weight above the 97.5th centile). 26% of the children had oral
      motor dysfunction and 33% were unable to self-feed. Although these problems were
      more prominent in children with severe forms of cerebral palsy, the results of
      the multivariate analyses suggested that lack of ability to self-feed was a
      significant independent risk factor for height growth retardation and
      underweight. Parents of 24 (15%) children reported that the family's quality of
      life was significantly impaired by the feeding problems of the child.
      INTERPRETATION: Our results are consistent with previous hospital-based studies
      and suggest that assessment of nutrition and growth should receive particular
      attention in the rehabilitation of children with cerebral palsy, in particular if
      the child is unable to self-feed.

PMID- 11446041
TI  - [Clinical risk index for small premature infants].
AB  - BACKGROUND: The clinical risk index for babies (CRIB) is a score given to
      extremely small prematures as a tool for expressing initial sickness. It was
      developed in order to compare results among different neonatal intensive care
      units (NICUs). MATERIAL AND METHODS: The CRIB score was determined for prematures
      with birth weight < or = 1,000 g born at the Central Hospital in Akershus during
      the 1995-99 period. The results are measured as the survival rate until
      discharge. RESULTS: 45 babies where treated at our NICU during this five-year
      period. Median gestation age was 27 weeks (range: 23-32 weeks), median birth
      weight was 875 g (range: 475-1,000 g), median CRIB was 4 (range: 1-16). The
      survival rate until discharge was 89%. To validate the CRIB score as a predictor
      for hospital mortality, a receiver-operating curve (ROC) was constructed. The
      area under the ROC curve was 0.93. INTERPRETATION: CRIB proved to be a good
      predictor for hospital mortality and seems a useful indicator for initial
      sickness.

PMID- 11446042
TI  - [Chronic intermittent vagal nerve stimulation--a new therapeutic approach in
      epilepsy].
AB  - BACKGROUND: Vagal nerve stimulation is a new non-pharmacological therapy for
      patients with refractory epilepsy. Introduced in USA in 1988, the treatment is
      based on animal experiments demonstrating that intermittent stimulation of the
      vagal nerve could prevent or reduce the frequency and/or duration of seizures.
      MATERIAL AND METHODS: At the National Hospital in Norway, 47 therapy-resistant
      patients have had a vagal nerve stimulator implanted since June 1993. We have
      used the Neuro-Cybernetic Prosthesis system from Cyberonics, consisting of a
      programmable pulse generator, a bipolar vagal nerve stimulator lead, a
      programming wand with accompanying software, and a hand-held magnet. The mean age
      of the population was 34.4 years (12-70 years). All had a long-standing epilepsy
      with frequent seizures, 36 (77%) had seizures every day. The majority (89%) had
      localization-related epilepsy. Mean follow-up time was 2.7 years (0.4-6.5 years).
      RESULTS: 16 patients (34%) responded to the treatment with > 50% reduction in
      seizure frequency. No one, however, became seizure free. 20 patients (43%) had no
      seizure reduction. 24 of the patients (51%) benefited from extra stimulation
      triggered by the magnet. The stimulation affected several types of seizures; most
      often a reduction in frequency of secondary generalised tonic-clonic seizures was
      noted. Hoarseness, coughing and a tingling sensation in the throat were the most
      frequently reported side effects occurring during stimulation. The patients
      tended to habituate to these side effects. In 14 patients (30%), the device has
      been explanted, mostly due to lack of efficacy. INTERPRETATION: Considering the
      fact that this patient group belongs to the most refractory part of the epilepsy
      population, the results are regarded as promising and they are in keeping with
      results from other studies. However, the role of vagal nerve stimulation in the
      future treatment of epilepsy is still not settled. Several questions remain
      unanswered, e.g. what are the exact mechanisms of action behind the seizure
      reducing effect, and which patients are most suitable for this treatment?

PMID- 11446043
TI  - [Is the epidural analgesia to blame when it comes to neurological complications
      following labor?].
AB  - BACKGROUND: One of every four parturient in Norway receives epidural analgesia
      during labour. Even though epidural analgesia is considered very safe, there is a
      tendency to blame the epidural whenever there are neurological complications
      after labour. METHODS: This paper presents a case report on a woman who developed
      femoral mononeuropathy after labour. The various neurological complications after
      labour are discussed. DISCUSSION: Gynaecologists, neurologists, mid-wives and
      even anaesthesiologists seem unaware of the fact that the incidence of
      neurological complications are four to five times higher as a result of the
      labour per se than complications caused by the epidural. Peripheral neurological
      symptoms after labour occur in 1:2-3,000 labours. Postpartum drop-foot and
      femoral mononeuropathy are the most frequent complications. Half of all
      parturients will experience low back pain during pregnancy and/or labour, and one
      in four will complain of headache in the immediate postpartum period. Urinary
      bladder dysfunction after pregnancy is not uncommon, but the incidence is the
      same among mothers who have received epidural analgesia and those who have not.
      Complications after epidural analgesia, such as haematoma, abscesses and direct
      nerve damage are extremely rare, but need immediate treatment.

PMID- 11446044
TI  - [Early CT signs in acute cerebral ischemia].
AB  - BACKGROUND: Patients who suffer from acute stroke should be examined with
      computed tomography (CT) of the brain immediately after admission. If evaluated
      systematically, this examination may give more information than just "bleeding
      excluded". MATERIAL AND METHODS: CT scans of the brain in four patients with
      acute ischaemic stroke admitted to our department illustrate the typical early CT
      signs in acute cerebral ischaemia. RESULTS: This article describes the systematic
      evaluation of a CT in acute stroke, when the following questions need to be
      answered: Is there a hyperdense middle cerebral artery sign (HMCAS), or
      hypodensity in other major intracranial arteries? Is there a hypodensity in the
      basal ganglia? Is there hypodensity (loss of cortical-subcortical discrimination)
      or oedema (decreasing volume of the Sylvian fissure) in the insular region? Is
      there hypodensity (loss of cortical-subcortical discrimination) or oedema
      (effacement of sulci or compression of ventricles) in other parts of the
      distribution of the middle cerebral artery or other arteries? INTERPRETATION: An
      early CT in acute stroke patients may yield valuable information if evaluated
      properly. The presence or absence of early CT sign have implications for
      diagnosis, prognosis, choice of supplementary examinations, and choice of
      treatment.

PMID- 11446045
TI  - [Steroid treatment of shock lung--tune for re-evaluation?].
AB  - BACKGROUND: The acute respiratory distress syndrome (ARDS) is one consequence of
      the body's systemic inflammatory response to a variety of powerful external
      stimuli. Glucocorticosteroids are highly effective anti-inflammatory drugs.
      During the last few years, the molecular mechanisms for their mode of action have
      been revealed; this has prompted a new wave of interest in corticosteroid
      treatment of systemic inflammatory states. Several clinical studies have been
      launched; the results have so far been promising. MATERIAL AND METHODS: We
      briefly discuss how new knowledge in this field may influence the use of
      corticosteroids in the treatment of ARDS. The presentation is illustrated by a
      case study. RESULTS: The patient was a 15-year-old boy with life-threatening and
      therapy-resistant ARDS. He was treated in a respirator in an intensive care unit
      (ICU). Two weeks after admission to the ICU, his situation was desperate. High
      dose corticosteroids were instituted, and during a five days' treatment his
      condition improved dramatically. After discontinuation of glucocorticoids he made
      further progress and was discharged from the ICU after another eleven days.
      INTERPRETATION: In this particular patient, administration of glucocorticoids had
      a striking effect. The influence of glucocorticoids on the activation of the
      transcription factor NF-kappa B and a resulting reduced synthesis of a number of
      key inflammatory molecules may be one explanation for the positive course.

PMID- 11446046
TI  - [Lung cancer screening--what now?].
AB  - BACKGROUND: Lung cancer is the most common cause of cancer death in developed
      countries. Because of the lack of efficient diagnostic tools for early detection
      and of efficient treatment for advanced disease, the prognosis of lung cancer is
      generally poor, with 10-15% surviving 5 years after diagnosis. Still, the
      majority of patients present with advanced disease. Stage IV disease is beyond
      cure and stage III disease is rarely curable with current therapies. Over the
      course of the last decade, rapid advances in molecular biology, pathology,
      bronchoscopy and radiology have provided a rational basis for earlier diagnosis
      and improved outcome. MATERIAL AND METHODS: This article reviews recent advances
      in the early detection of lung cancer by low-dose spiral CT scanning. The review
      is based on a literature search in Medline and data presented at the 3rd
      International Conference on Screening for Lung Cancer in New York in October
      2000. RESULTS: The most promising advent has been the development of low-dose
      spiral CT as a screening tool for lung cancer. The advantage of this method is
      the possibility of diagnosing small peripheral tumours before they have spread to
      regional or distant areas. INTERPRETATION: A shift in the therapeutic paradigm
      from targeting clinically manifest advanced lung cancer towards asymptomatic
      preinvasive and early invasive cancer is occurring. If the altered stage
      distribution (87% stage I) as seen in three non-randomized population-based
      studies is real, CT screening may raise the lung cancer cure rate above 60%.

PMID- 11446047
TI  - [Lovseth's manoeuvre in breech presentation--"best and safest"].
AB  - During the first half of 20th century, the most important goal in obstetrics was
      to make vaginal deliveries safer. Two Norwegian gynaecologists put their mark on
      this development: Christian Kielland's (1871-1941) obstetric forceps and Jorgen
      Lovset's (1896-1981) manoeuvre in breech presentation. Lovset made several other
      contributions to Norwegian and international obstetrics, in particular a series
      of innovations. In his old age he advocated obstetrics as a form of art and
      underlined the importance of learning "what is necessary to be worthy of the name
      of obstetrician". He experienced the dramatic change in attitude to and frequency
      of caesarean section.

PMID- 11446048
TI  - [St. Johns wort].

PMID- 11446049
TI  - [The hidden nature of health].
AB  - This essay starts with a story about my meeting with a local medical culture as a
      young doctor. The point of the story is that a situation can be experienced and
      understood in different ways. The kind of knowledge one brings into a situation
      opens up for or prevents new understanding from developing. The concept of health
      has lost its content based on the experience and knowledge of everyday life; this
      content is replaced by concepts from medicine as the science of sickness. Health
      is linked to "well-being". The nature of health is hidden. It appears as
      something we are missing when threatened by pain, symptoms, illness or sickness.
      The medical knowledge of sickness is expert knowledge; the experience of health,
      on the other hand, is part of the experience of being human. Medical expert
      knowledge tends to occupy the field where health can be experienced. Medicine
      practiced as a cultural meeting between persons of equal human standing means
      that both doctors' and patients' knowledge can be taken seriously. The concept of
      health can be rehabilitated as a life-world concept. This requires more than just
      an intellectual effort; it requires the courage to see how our thinking has been
      shaped through scientific knowledge. This, in turn, requires of us the inner
      strength to cope with situations we do not understand.

PMID- 11446050
TI  - [Voice of shame--silence, eloquence and rage in the therapeutic relationship].
AB  - Is shame out of fashion? The first part of this article discusses how the concept
      of shame has changed in modern western culture, with a shift from collective
      definitions of norms towards personal experience. The second part is a
      phenomenological description of shame and how shame can be expressed and
      experienced in therapeutic relationships. Shame is something we do want, and
      something we do not want. It regulates both self-esteem and intimate
      relationships. It protects the psychological self from invasion. But too much
      shame is destructive. The main expression of deep shame is silence; it is
      shameful to speak about one's shame. But deep and pathological shame can be
      masked in other forms of presentation, "the voices of shame". In addition to
      silence the article describes "the psychopathology of normalcy", hesitation,
      depression, alexithymia, rage, envy, contempt, grandiosity and shamelessness.
      Finally, the article discusses how to escape from destructive feelings of shame.

PMID- 11446051
TI  - [Destiny-zapping--medical education, students' world view and the ethical
      challenge].
AB  - Three medical students describe their search for professional and personal
      identity midway through medical school. The article focuses on their concrete
      experience of human suffering and vulnerability, which is set against elements
      from the relational ethics of Danish philosopher KE Logstrup. Logstrup's ontology
      is based on a relational understanding of being human, and implicitly opposes the
      strongly objectivating and individualised view of human existence promoted
      through the experiences of everyday medical education.

PMID- 11446052
TI  - [Empowerment and stronger patient's position--an educational model].

PMID- 11446053
TI  - [Physician's right of reservation in connection with induced abortion].

PMID- 11446054
TI  - [Familial hypercholesterolemia--prognosis and treatment].

PMID- 11446055
TI  - [Genetic screening and treatment in familial hypercholesterolemia].

PMID- 11446056
TI  - [Efficient treatment of depression?].

PMID- 11446057
TI  - [Habilitation of children with sensory disorders].

PMID- 11446058
TI  - [Selective serotonin reuptake inhibitors--new adverse effects?].

PMID- 11446059
TI  - [An important measure for better decision procedures].

PMID- 11446060
TI  - [Robert May the friend].

PMID- 11446061
TI  - [Robert May (1912-1984). His scientific work].

PMID- 11446062
TI  - [Diagnosis of thrombophilia]].
AB  - Using laboratory testing, coagulation alterations can be detected in about 50% of
      familial thrombophilia. Most common hereditary coagulation defects leading to
      enhanced thrombosis risk are aPC resistance/Factor V Leiden mutation, protein C-
      and S-deficiency, prothrombin 20210A polymorphism and antithrombin deficiency.
      Moreover, elevated plasma levels of homocysteine also are associated with
      enhanced thrombosis risk. Severity of thromboembolic risk depends upon type of
      coagulation defect, hetero- or homocygosity and occurrence of additional acquired
      risk factors like immobilisation. Therapy of thromboembolic diseases must always
      be planned considering both clinical circumstances and laboratory findings.

PMID- 11446063
TI  - [Effectiveness of locoregional rt-PA lysis in acute leg and arm vein thrombosis].
AB  - 39 patients suffering from a thrombosis of the peripheral venous system were
      treated with a loco-regional lysis, using rt-PA. Two cycles of 40 mg rt-PA a day
      were applicated by means of a special drainage-management, using perforans veins.
      During lytic therapy, 20,000 to 30,000 IE of unfractionized heparin were
      additionally administered. Laboratory work including aPTT and fibrinogen
      measurement was performed every 8 hours. Additionally a phlebography was
      performed after 24 hours. Patients received an anticoagulative therapy using
      sintrom or marcumar the following 3 months. We obtained a successful thrombolysis
      without any major complications in 90%. Minor complications included 3 peripheral
      pulmonary embolisms. Duplex sonographic and plethysmographic follow up was
      performed in 25 patients one year after operation. In two patients with ankle
      edema insufficient valves at the popliteal vein were found with both diagnostic
      modalities. 23 patients showed no signs of insufficient valves neither clinically
      nor at duplex sonography and plethysmography. The locoregional lysis appears to
      be an effective method for the treatment of acute peripheral vein thrombosis.

PMID- 11446064
TI  - [Conservative therapy of acute pelvic-leg vein thrombosis].
AB  - During the acute phase of the disease the aim of conservative treatment of DVT is
      relief of symptoms as well as prevention of thrombus progression and pulmonary
      embolism. In the chronic phase treatment should prevent recurrence and post
      thrombotic syndrome. Besides general measures such as compression therapy,
      elevation of the leg and mobilisation anticoagulation therapy with heparin and
      coumarin has been proved to be successful. Even though not more effective or
      safer low-molecular weight heparin has recently replaced unfractionated heparin
      in the initial treatment of DVT mainly because of its more convenient use
      allowing modern ambulatory and outdoor treatment. Doses depend on the kind of
      heparin used. In the secondary prevention therapy with coumarins, an INR of 2-3
      is generally accepted whereas the duration of oral anticoagulant therapy is under
      discussion. Compression therapy is recommended for at least 2 years, in case of
      post-thrombotic syndrome life-long therapy is necessary. When comparing the
      effectiveness of DVT-treatment today with the results in the preanticoagulant
      era, the modern treatment is more effective, safe and cost-effective; it also
      guarantees more quality of life, but the long-term results have to be improved.

PMID- 11446065
TI  - [Stent or bypass? Treatment results in benign central venous obstruction].
AB  - PURPOSE: Surgical treatment of central venous obstruction is difficult and
      sometimes hazardous, but not always successful. Sufficient palliation of malign
      stenoses can often be achieved by stent implantation. Thus it seems necessary to
      define the relative value of stenting in comparison to surgical reconstruction
      for the treatment of benign obstructions, with special respect to the long-term
      results. METHODS: Between 1990 and 1999, 64 central venous stents were implanted.
      Mediastinal vein obstructions in 23 hemodialysis patients were treated with a
      total of 35 stents. 29 iliofemoral stents were implanted following operative or
      conservative treatment of 21 venous thromboses. During the same time period, only
      6 surgical bypasses were performed (all in hemodialysis patients). All patients
      were followed-up prospectively. Patency rates were calculated according to the
      life table-method. RESULTS: Following stent implantation one asymptomatic
      pulmonary stent embolism (2.3%) and three stent misplacements (6.8%) were
      documented. Two of the latter were successfully treated with another stent. In
      the surgical group, one patient died at eight weeks due to late complications of
      a cephalosporine-associated Lyell syndrome. One to five year patency rates were
      not significantly different among the three groups. CONCLUSION: For benign
      central venous stenoses in hemodialysis patients and following iliofemoral venous
      thrombosis, stent implantation can be recommended as a simple, safe, and durable
      means to restore patency. Still there is a role for surgery in severely
      symptomatic central venous occlusions when stent implantation is impossible or
      has failed.

PMID- 11446066
TI  - [Balloon dilatation and stent implantation in malignant and benign stenoses of
      the central venous system].
AB  - Compared with the excellent good results on the arterial side, venous angioplasty
      combined with stent-application was described relatively late in the literature,
      dealing in the majority of cases with palliative tumour stenoses of the superior
      and inferior vena cava. Recanalization of benign stenoses, especially of the
      pelvic venous spur (May/Thurner; syn. Pelvic compression syndrome, Cockett) was
      realized so far only in a limited number of cases. We have performed this
      interventional therapy since 1991 in 21 patients (female: 16, male: 5), with good
      long-term results in 18 cases. According to the special patho-anatomy of the
      "spur", developing intimal proliferation and progressive stenosis at the left
      sided ilio-caval junction in about 20% of the average adult population, a
      restrictive indication is, however, mandatory. According to strong clinical
      symptoms (severe varicosis and leg oedema at the left-sided lower extremity),
      phlebographic and functional parameters (won by central venous blood pressure
      measurements) are indicating selected cases for this curative treatment.

PMID- 11446067
TI  - [Early and late results of transperitoneal thrombectomy in thrombosis of the
      inferior vena cava].
AB  - Acute inferior vena cava thrombosis is a rare clinical feature with unknown
      incidence. A clear evidence about the best treatment does not exist. Especially
      the indications for surgical therapy and their clinical results are published
      only in a few reports. So the aim of this study was to take a look to our
      experience and make an evaluation of the combined transcaval and transfemoral
      venous thrombectomy. In a retrospective study of the past 12 years 19 patients
      with a mean age of 28.5 years, 15 women and 4 men, showing ascension of a
      iliofemoral clot to the vena cava were treated by transperitoneal and
      transfemoral thrombectomy. The mean thrombus age was 7 days, 2 patients had
      bilateral iliofemoral thrombosis. Simultaneously a transfemoral thrombectomy and
      transcaval thrombectomy were performed after exposure of the vena cava inferior
      via transabdominal approach. In all cases a venous patency could be achieved, 3
      times a re-thrombectomy within 1 week was necessary. One intraabdominal hematoma
      was revised surgically. One patient died on the first postoperative day because
      of a fulminant lung embolism. After a mean follow-up of 6 years 3 patients did
      not have any symptoms of post-thrombotic sequelae, 13 had mild and only one
      patient moderate post-thrombotic syndrome. The combined transperitoneal and
      transfemoral venous thrombectomy of the vena cava inferior represents a safe and
      effective treatment of the acute thrombosis of the vena cava inferior. Severe
      post-thrombotic sequelae especially in young women may be avoided.

PMID- 11446068
TI  - [Reconstructive venous valve surgery].
AB  - The indication for venous valves surgery has to consider morphological and
      functional aspects. 36 reconstructive valve repair procedures and the long-term
      results are reported. The procedures need surgical skill and a meticulous
      operation technique. Primary idiopathic valvular incompetence can be treated with
      a direct valvuloplasty (Kistner). The leaflets of the floppy valve become
      shortened either by an open repair or with a closed procedure. Patients suffering
      from post-thrombotic syndrome showing intact valves in the deep femoral vein may
      undergo a transposition operation. In this case the superficial femoral vein is
      implanted end to side into the deep femoral vein distally to a proximal valve.
      The best results in post-thrombotic syndrome are achieved with a free
      transplantation of a venous valve from the axillary vein into the superficial
      femoral or into the popliteal vein (Taheri). Postoperatively the patients are
      anticoagulated and have to wear a compressing stocking (Grade III). The results
      of direct valvuloplasty (Kistner) and valve transplant (Taheri) are satisfactory,
      whereas the results of transposition seem to be disappointing. Good results are
      depending mostly on a correct indication for the operation and on avoiding the
      contraindications.

PMID- 11446069
TI  - [Phlebological diagnosis. Phlebography of the veins of the lower extremity].
AB  - Phlebography should be weighed up against the current sonographic techniques
      (Doppler and Duplex) applied for visualization of venous disorder along the lower
      extremity veins, following a decision tree considering completeness and quality
      of documentation wanted, invasiveness and clinical consequences expected in the
      individual case. Ascending leg phlebography, incorporating Valsalva's manoeuvre,
      means the up-to-date standard technique, offering morphologic and functional
      information. Varicography and additional phlebographic techniques are considered
      to be additive, solving special problems, having not been visualized by the
      standard phlebography before. Combined phlebography and peripheral blood pressure
      measurements may improve the output of functional informations within one
      session. Quality standards of phlebography have to include standardized technique
      of phlebography, of documentation and interpretation, dealing with the special
      aspects of varicose syndrome, acute thrombosis and the post-thrombotic syndrome.

PMID- 11446070
TI  - [Chronic venous compartment syndrome].
AB  - Various forms of compartment syndrome can now be distinguished. Acute compartment
      syndrome is the result of a discrepancy between the volume of the compartment and
      its contents. This leads to increased pressure at rest and during load, which
      cuts off the micro-circulation and hence destroys the intracompartmental
      structures. Chronic compartment syndrome had only been seen in athletes and
      soldiers up to now. The disease mainly affects the anterior compartment and the
      fibular muscle group, and only rarely the lateral muscle compartment. In the
      course of severe venous diseases, a chronic venous compartment syndrome develops
      which is fundamentally different from the clinical pictures previously known. The
      cicatricial destruction of the crural fascia exerts an effect on the
      intracompartmental pressure with every step the patient takes. In severe cases,
      this results in considerable changes in the muscles involving chronic ischaemia
      associated with necrosis and glycogen deficiency. Further investigations are
      necessary in order to define the clinical picture, particularly by measuring the
      intracompartmental pressure under dynamic and standardised conditions. We suggest
      also making a verbal distinction between the two forms: a chronic exertional
      compartmental syndrome and a chronic venous compartmental syndrome.

PMID- 11446071
TI  - [Chronic osteomyelitis of the ilium after autologous bone harvesting in Albers
      Schonberg osteopetrosis. A case report].
AB  - We report the treatment of chronic osteomyelitis of the iliac wing after
      autologous bone harvesting in a 17-year old boy with osteopetrosis. A partial
      resection of the iliac wing was performed followed by systemic antibiotic
      treatment. The wound healing was without complications. We consider autologous
      bone harvesting in patients with osteopetrosis to be a critical procedure due to
      the higher risk of infection.

PMID- 11446072
TI  - [Walther Kausch (1867-1928) and his significance in pancreatic surgery].
AB  - The very interesting medical career of Walther Kausch, student of Johannes
      Mikulicz-Radecki, is portrayed. The first successful partial
      pancreatoduodenectomy of the world in 1909 was his great surgical feat. The
      question why Kausch did not go on this promising way will be discussed. In future
      it would be appropriate to speak of the "Kausch-Whipple-Operation".

PMID- 11446073
TI  - [Laparoscopic left pancreas resection in tumors. Initial clinical experiences].
AB  - Laparoscopic pancreatic resections are rare procedures with left resections
      considered as a special subject. In animal trials and in 26 operations performed
      so far, this laparoscopic procedure was assessed positively. The operations were
      carried out mainly for benign diseases. From November 1998 to July 2000, five
      laparoscopic left pancreatic resections were performed in our hospital for the
      following diseases: adenocarcinoma (2), neuroendocrine carcinoma, highly
      malignant T-cell lymphoma, and cyst adenoma. In 3 patients the pancreatic
      resection was completed by other procedures: the case of T-cell lymphoma by
      gastrectomy and left side hemihepatectomy, the case of advanced pancreatic
      carcinoma by resection of a liver metastasis, and the case of cyst adenoma by a
      partial adrenalectomy. There was no patient suffering from intra- or
      postoperative complications. The benefit is mainly noticed in the early
      postoperative period. All required oncosurgical criterias were fulfilled.

PMID- 11446074
TI  - Consensus statement on submission and publication of manuscripts.

PMID- 11446075
TI  - [Therapy of inguinal hernia (2)].

PMID- 11446076
TI  - [Role of radiotherapy in the treatment of cerebral meningiomas].
AB  - Cerebral meningiomas account for 15-20% of all cerebral tumours. Although seldom
      malignant, they frequently recur in spite of complete surgery, which remains the
      cornerstone of the treatment. In order to decrease the probability of local
      recurrence, radiotherapy has often been recommended in atypical or malignant
      meningioma as well as in benign meningioma which was incompletely resected.
      However, this treatment never was the subject of prospective studies, randomized
      or not. The purpose of this review of the literature was to give a progress
      report on the results of different published series in the field of methodology
      as well as in the techniques of radiotherapy. Proposals for a therapeutic choice
      are made according to this analysis. For grade I or grade II-III meningiomas,
      limits of gross tumor volume (GTV) include the tumour in place or the residual
      tumour after surgery; clinical target volume (CTV) limits include gross tumour
      volume before surgery with a GTV-CTV distance of 1 and 2 cm respectively.
      Delivered doses are 55 Gy into CTV and 55-60 Gy and 70 Gy into GTV for grade I
      and grade II-III meningiomas respectively.

PMID- 11446077
TI  - [Comparison of conventional and conformational dosimetry in radiotherapy of
      cerebral neoplasms].
AB  - PURPOSE: We prospectively compared a conventional treatment planning (PT2D) and 3
      dimensional conformal treatment planning (PT3D) for radiotherapy of cerebral
      tumours. PATIENTS AND METHODS: Patients treated between 1/10/98 and 1/4/99 by
      irradiation for cerebral tumours were analysed. For each case, we planned PT2D
      using conventional orthogonal x-ray films, and afterward, PT3D using CT scan.
      Gross tumor volume, planning target volume and normal tissue volumes were
      defined. Dose was prescribed according to report 50 of the International
      Commission on Radiation Units and Measurements (ICRU). We compared surfaces of
      sagittal view targets defined on PT2D and PT3D and called them S2D and S3D,
      respectively. Irradiated volumes by 90% isodoses (VE-90%) and normal tissue
      volumes irradiated by 20, 50, 90% isodoses were calculated and compared using
      Student's paired t-test. RESULTS: There was a concordance of 84% of target
      surfaces defined on PT2D and PT3D. Percentages of target surface under- or-over
      defined by PT2D were 16 and 13% respectively. VE-90% was decreased by 15% (p =
      0.07) with PT3D. Normal brain volume irradiated by 90% isodose was decreased by
      27% with PT3D (p = 0.04). CONCLUSION: For radiotherapy of cerebral tumors using
      only coplanar beams, PT3D leads to a reduction of normal brain tissue irradiated.
      We recommend PT3D for radiotherapy of cerebral tumors, particularly for low-grade
      or benign tumors (meningiomas, neuromas, etc.).

PMID- 11446078
TI  - [The role of high-energy imaging in a radiotherapy service and its incorporation
      in a network].
AB  - To directly compare the clinical efficacy of electronic to film portal images and
      the advantages of comparing directly on the monitor the simulation image and the
      portal image. MATERIAL AND METHODS: This study was designed to compare clinical
      efficacy of electronic to film portal images acquired using a liquid matrix ion
      chamber electronic portal imaging device (EPID) and a conventional film system.
      Two radiation oncologists served as observers and evaluated a total of 30 sets of
      images for three different treatment sites: lung, pelvis, and head/neck. Each set
      of images included a simulation image, a portal film, a video paper print of
      electronic portal images, and a video prints of electronic portal images. Four to
      six anatomical landmarks were selected from each treatment site. Each observer
      was asked to rate each landmark in terms of its clinical visibility and to rate
      the ease of making the pertinent verification decision in the corresponding
      electronic and film portal images with the aid of the simulation image. The time
      needed to obtain and analyse a conventional portal image and an EPID would be
      analysed for the radiotherapist and the medical technicians. RESULTS: Ratings for
      the visibility of landmarks and for the verification decision of treatment ports
      were similar for electronic and film images for most landmarks. However,
      vertebral bodies and several landmarks in the pelvis such as the acetabulum and
      pubic symphysis were more visible in the electronic portal images than in the
      portal film images. For the medical technicians, the EPID is more comfortable,
      and they do not need to develop any images. CONCLUSION: The visibility of
      landmarks in electronic portal images is comparable to that in film portal
      images. Verification of treatment ports based only on electronic portal images
      acquired using an electronic portal imaging device is generally achievable. Thus
      the integration of the EPID and simulation image in a network provides more
      flexibility in the daily work of a medical radiotherapy team.

PMID- 11446079
TI  - [Breast-conserving surgery and irradiation for early breast cancer: value of
      surgical clips in the surgical cavity].
AB  - PURPOSE: To evaluate, qualitatively and quantitatively, the role of surgical
      clips in planning the tumor bed electron or brachytherapy boost in patients
      undergoing breast-conserving surgery and radiotherapy. PATIENTS AND METHODS: In
      60 patients with breast cancer stage I or II, the excision cavity boundaries were
      marked by clips at surgery. Patients received a boost with brachytherapy (n = 51)
      or electron beam (n = 9) after whole breast irradiation. The boost target volume
      was first planned using clinical, mammography and operative information and its
      accuracy evaluated by screening the surgical clips and, if necessary, adjusting
      the field to encompass all clips and to include the scar. Dosimetry was
      retrospectively performed for each brachytherapy patient and for each surgical
      clip. RESULTS: It was necessary to modify the target volume field in 11 cases
      (18%). The average dose received by the surgical clips was 116.1% of the dose
      delivered to the reference isodose (median: 101.75%, range: 16-457%). However,
      dose heterogeneity was important in the same patient and between patients.
      CONCLUSION: Delineation of the boost target volume with surgical clips is more
      accurate than with clinical landmarks alone but this technique does not allow
      measurements of the clip-chest wall and clip-skin distances. Virtual simulation
      with CT-scan cuts is recommended for optimising boost planning.

PMID- 11446080
TI  - A retrospective analysis of the results of p(65) + Be neutrontherapy for the
      treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part
      I: Survival and progression-free survival.
AB  - PURPOSE: To retrospectively evaluate survival, progression-free survival (PFS)
      and biological response in a series of patients irradiated with mixed
      neutron/photon beams for locally advanced prostate cancer in our institution.
      PATIENTS AND METHODS: Three hundred and eight patients were treated between
      January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1
      tumors after radical prostatectomy. Neoadjuvant androgen deprivation was given in
      106 patients. The treatment protocol consisted of a mixed photon/neutron
      irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy
      (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA
      determinations were available in practically all cases. Study endpoints were
      overall survival (OAS) and progression-free survival (PFS). The Cox proportional
      hazard regression model was used to investigate the prognostic value of baseline
      characteristics on survival and progression-free survival were a progression was
      defined as local, regional, metastatic or biological progression. Mean age was 69
      years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5
      160) in those receiving neoadjuvant hormonotherapy; seven patients only had an
      initial PSA < or = 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4%
      were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38%
      and III in 14% (5% unspecified). RESULTS: The median follow-up was 2.8 years (0
      7.8). Five-year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year
      progression-free survival (PFS) was 64% (95% CI: 54-74%) for the entire series.
      PFS in patients with an initial PSA > or = 20 ng/mL was the same. PFS could be
      predicted by two optimal Cox regression models, one including histological grade
      (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including
      histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic
      factors for overall survival were PSA and age. Biological responses with PSA <
      1.5 ng/mL, < 1 ng/mL and < 0.5 ng/mL at any time after treatment were documented
      in 70%, 61% and 47% of the patients, respectively. CONCLUSION: Five-year OAS was
      79%, PFS was 64%, and biological response was 70% for prostate cancer patients
      treated with mixed photon/neutron beams as applied at Louvain-la-Neuve, which are
      good results as compared with the literature. The usual prognostic factors were
      confirmed.

PMID- 11446081
TI  - [Method of radiotherapy planning for head and neck tumors using simulated CT
      images and radiographic data, developed at the Gustave Roussy Institute].
AB  - The paper deals with the recent improvements introduced in the most usual method
      applied in the Institut Gustave Roussy radiotherapy department for obtaining the
      anatomical data of patients treated for head and neck tumors. For each of these
      patients, five to seven transverses slices and a lateral radiographic film are
      taken from a Mecaserto simulator-CT. The anatomical representation of the patient
      sagittal plane is carried out from the digitalisation of the radiographic film on
      a Vidar Vxr-12 Plus film scanner and integrated into the Dosigray dose
      calculation programme in order to be used as a support for the laying out of the
      dose distribution in reference to the treatment. The sagittal anatomical
      representation obtained from the radiographic film digitalisation is compared
      with the one resulting from the interpolation between a limited number of
      irregularly-spaced transverse slices taken on the simulator-CT. The method using
      the simulator-scanner transverse slices and the radiographic film digitalisation
      represents an interesting alternative for obtaining an anatomy simulation
      representative of the patient in hospitals where a scanner is not available full
      time for the needs of the radiotherapy process.

PMID- 11446082
TI  - [Hypothyroidism after external radiotherapy. Fifteen cases].
AB  - Hypothyroidism frequency is estimated to be between 10 and 45% after radiotherapy
      alone, and 40 to 67% after radiotherapy associated with thyroidectomy. This
      hypothyroidism is infraclinical in 60% of the cases. Our study concerned 15 cases
      of hypothyroidism after external radiotherapy delivered between and 1991 and
      1999. An irradiation of the cervical, cerebral and thorax regions was indicated
      for different types of cancers. Larynx carcinoma epidermoid was the most frequent
      cancer (seven cases); the radiation treatment used cobalt 60 with conventional
      fractionation, i.e., 2 Gy per treatment, five treatments a week. In nine cases,
      the hypothyroidism was discovered during a systematic examination; it was
      clinically evident in the six remaining cases. Hypothyroidism appeared after an
      irradiation dose average of 50 Gy (extremes 30-65 Gy). The average duration of
      the irradiation was about 7 weeks and the hypothyroidism appeared in a mean 22
      months. In all cases, the substituting treatment was initiated with a favorable
      progression. Faced with the risk of hypothyroidism, it is necessary to check
      patients who have undergone external irradiation of the neck.

PMID- 11446083
TI  - [Secondary mandibular fibrosarcoma after chemoradiotherapy for undifferentiated
      nasopharyngeal carcinoma. Report of a case and review of the literature].
AB  - Secondary tumours to radio- and/or chemotherapy have rarely been reported after
      treatment for head and neck cancers. We report a case of mandibular fibrosarcoma
      observed 7 years after chemoradiotherapy for undifferentiated nasopharyngeal
      carcinoma in a patient treated when 20 years old.

PMID- 11446084
TI  - [Non-small-cell lung cancer. Analysis of survival according to treatment].

PMID- 11446085
TI  - On the need for greater regulation of medical devices.

PMID- 11446086
TI  - Dark skin tissue reaction in laser assisted hair removal with a long-pulse ruby
      laser.
AB  - BACKGROUND: Photo-epilation has become an accepted modality for the removal of
      unwanted hair. However, adverse effects may occur in darker skin patients.
      Treatment with the ruby laser is generally advised for skin types I-III.
      Treatment of over 3000 patients (skin types I-III) in our clinic has resulted in
      a minimal percentage (approximately 3%) of adverse effects. Increasing pulse
      duration should allow the epidermis to cool and thus minimize thermal damage so
      that treatment can be extended to dark skin patients. OBJECTIVES: The purpose of
      our study was to compare tissue reaction in dark skin patients (skin type IV)
      after treatment with a long-pulse (20 msec) ruby laser and compare the reaction
      with a 1 msec ruby laser treatment. RESULTS: Hair removal efficacy was determined
      to be similar with both pulse durations, but tissue reaction was more severe,
      including eschar and hypopigmentation, following treatment of dark skin patients
      with the 1 msec protocol. Increasing the pulse duration to 20 msec appears to
      result in safe and efficacious ruby laser treatment even for darker skinned
      patients.

PMID- 11446087
TI  - Radical surgery for ingrown nails by partial resection of the nail plate and
      matrix using a carbon dioxide laser.
AB  - BACKGROUND: We report here on the successful surgical treatment of ingrown nails
      by partial resection of the nail plate and matrix using a carbon dioxide laser.
      MATERIALS AND METHODS: The subjects of this study were 28 patients (37 cases) who
      visited our outpatient clinic with the chief complaint of ingrown nails of the
      great toe between October 1995 and October 1999. They included 12 males and 25
      females. Patient age ranged from six to 72 years (mean 26.5 years), and the post
      operative follow-up period ranged from eight to 48 months (mean 23.2 months).
      RESULTS: Clinically, this treatment was excellent in terms of operating time
      reduction, mitigation of mid-operative and post-operative bleeding and pain, and
      treatment period reduction. Furthermore, no recurrences were observed during the
      study period. CONCLUSIONS: Judging from the good therapeutic results and improved
      quality of life of patients, this treatment is expected to be commonly used in
      the future.

PMID- 11446088
TI  - Treatment of scars with a pulsed Er:YAG laser.
AB  - BACKGROUND: Numerous revision procedures such as surgical excision, intralesional
      steroid injection, cryotherapy, dermabrasion, soft tissue augmentation, chemical
      peeling and laser therapy are available for the correction of various types of
      scars. Recently, Er:YAG laser resurfacing has proved to be a useful and safe
      means for several kinds of scars. OBJECTIVE: The purpose of this study was to
      assess the efficacy and safety of pulsed Er:YAG laser scar resurfacing for the
      various types of scars induced by trauma, burns, or surgery. METHODS: This study
      included 36 patients with various types of scars resulting from picking,
      scratching, knife injury, laceration, car accident, simple surgical excision,
      focal burn and focal inflammation. Twelve of these patients were treated for
      hypertrophic scars, 20 for depressed scars, and four for burn scars. The pulsed
      Er:YAG laser with a 2-mm handpiece at the setting of 500-1200 mJ/pulse at 3.5-9 W
      was used. Photographs were obtained at baseline and 2-week intervals
      postoperatively. The results of laser treatment were assessed by two independent
      physicians and the surgeon according to contour, skin texture and color. RESULTS:
      In all, 9 of 12 hypertrophic scars, 17 of 20 depressed scars, and two of four
      burn scars were improved more than 50%. In one patient who had a depressed scar,
      minimal postinflammatory hyperpigmentation was observed 3 months after laser
      treatment. Mild erythema was sustained 4 months after laser treatment in one
      patient with a depressed scar and in all patients with burn scars. No other side
      effects were observed. CONCLUSION: A pulsed erbium:YAG laser is an effective and
      safe treatment modality for scar revision.

PMID- 11446089
TI  - Microwave delivery system for lower leg telangiectasia.
AB  - BACKGROUND: The treatment of telangiectasia of the lower limbs has mainly
      consisted of injection sclerotherapy and the use of a variety of different
      lasers. Some patients do not respond well and others have a variety of local side
      effects. Alternative treatments would be helpful in managing many patients.
      OBJECTIVE: To evaluate a microwave device for the treatment of lower limb
      telangiectasia less than 2 mm in diameter. METHODS: Twenty subjects were enrolled
      and evaluated with clinical and photographic assessment before and for up to 3
      months after treatment. RESULTS: Improvement was seen in 18 of 20 patients. Two
      patients achieved greater than 75% improvement, six patients 51-75%, four
      patients 26-50% and six patients less than 25% improvement. CONCLUSION: A
      microwave delivery device improved lower limb telangiectasia in 18 of 20
      patients.

PMID- 11446090
TI  - Treatment of port wine stains using the pulsed-dye laser at 585 nm with the
      dynamic cooling device.
AB  - Port wine stains (PWS) are common vascular malformations appearing more
      frequently on the face and neck. One of the most prevalent treatment modalities
      for PWS is the pulsed-dye laser (PDL). The first generation PDL was limited to a
      450 microseconds pulse width which was inadequate for the treatment of larger
      caliber vessels. Second generation PDLs have pulsed widths approximately three
      times longer (1.5 ms). This, along with the dynamic cooling device (DCD), which
      allows the safe use of higher fluences, should result in more clinical
      improvement in the treatment of PWS that were previously resistant or minimally
      responsive to first generation PDL treatment. We report a case of a 29-year-old
      white male with extensive PWS on the left face, left neck, and back, which
      displayed only mild changes with the first generation PDL. However, the use of
      the 1.5 ms PDL at 585 nm at high fluences in conjunction with the DCD resulted in
      marked improvement of the patient's PWS.

PMID- 11446091
TI  - Successful removal by ruby laser of darkened ink after ruby laser treatment of
      mismatched tattoos for acne scars.
AB  - Cosmetic tattoos are becoming increasingly popular. Elimination of cosmetic
      tattoos is sought because of misplacement or migration of tattoo pigment,
      allergic reactions to the various pigments or dissatisfaction of the customer for
      various reasons. Removal of unwanted pigment is a domain of laser surgery using
      various Q-switched laser systems, such as the ruby, alexandrite, pulsed dye and
      Nd:YAG lasers. Dark colours are easily removed by these lasers, whereas red, pink
      and skin-toned pigment may turn black if exposed to Q-switched laser light. This
      ink-blackening occurs because Q-switched lasers heat up the pigments, which
      consist of ferric oxide, and reduce them into ferrous oxide, which is black.
      Laser-induced black ink is not always readily removed. A successful ruby laser
      removal of laser-induced blackened cosmetic tattoos for acne scar camouflage is
      reported. The advantageous outcome in this case contrasts with other published
      cases where laser-darkened pigment had to be removed by other measures, or was
      permanent. Test site treatment can limit the problem to some degree but, in
      addition to test-treating, some kind of 'tattoo identification card' could help
      to prevent problems in this field and allow 'in vitro' test treatment.

PMID- 11446092
TI  - Sarcoidosis presenting as tattoo granuloma inadvertently treated with laser
      therapy.
AB  - A patient presenting with nodules in his tattoos was referred for laser
      treatment, following which there was a diagnosis of cutaneous and pulmonary
      sarcoidosis. Nodular change involving several different tattoo colours is
      characteristic of sarcoidosis.

PMID- 11446093
TI  - The treatment of urticaria pigmentosa with the frequency-doubled Q-switch Nd:YAG
      laser.
AB  - Urticaria pigmentosa is a chronic benign proliferation of mast cells in the skin
      that presents considerable cosmetic disability, for which there is no current
      successful treatment. We describe a 30-year-old woman with urticaria pigmentosa
      in whom treatment with the Nd:YAG laser produced a significant improvement in the
      clinical appearance of the eruption, with some recurrence after 9 months. This
      procedure has not previously been described, and we propose this as a potential
      new treatment modality for urticaria pigmentosa.

PMID- 11446094
TI  - Vascular mechanisms in laser hair removal.

PMID- 11446095
TI  - Laser resurfacing of the face.

PMID- 11446096
TI  - Selective non-ablative wrinkle reduction by laser.
AB  - BACKGROUND AND OBJECTIVES: Skin resurfacing and wrinkle removal is a large
      medical laser market. However, the rate of undesirable side effects is high and
      sometimes is not warranted by the aesthetic improvement observed. The authors
      have evaluated the potential benefits of an approach to selective non-ablative
      wrinkle reduction. MATERIALS AND METHODS: This technique selectively targets the
      microvasculature which plays a key role in the stimulation of enhanced collagen
      production. RESULTS: The study reported shows that application of the laser
      parameters described enhances collagen production by an average of 84%, measured
      72 hours after a single laser treatment. This is achieved whilst leaving the skin
      barrier intact and with no adverse pigmentary changes. The study further shows
      that a cosmetic improvement is observed with an average value of 1.88 reduction
      in wrinkle appearance as measured on the Fitzpatrick Wrinkle Severity scale. This
      improvement was achieved with one brief treatment and no reported incidence of
      side effects. CONCLUSION: In conclusion, the treatment modality described may be
      a new approach to the treatment of wrinkles.

PMID- 11446097
TI  - Vaccines and vaccinations. The strategic issues.
AB  - The rapid proliferation of companion animal vaccines, advances in diagnostic and
      vaccine technology, and concerns over vaccine safety are clearly among the most
      important issues practicing veterinarians face as we enter the 21st century.
      Although many would argue that these are already issues, the future promises to
      be especially challenging as the vaccines we currently use and the protocols we
      recommend undergo unprecedented review.

PMID- 11446098
TI  - Feline vaccination guidelines.
AB  - The 1998 Report of the American Association of Feline Practitioners and Academy
      of Feline Medicine Advisory Panel on Feline Vaccines was developed to help
      veterinary practitioners formulate vaccination protocols for cats. The current
      panel report updates information, addresses questions, and speaks to concerns
      raised by the 1998 report. In addition it reviews vaccine licensing, labeling,
      and liability issues and suggests ways to successfully incorporate vaccination
      protocol changes into a private practice setting.

PMID- 11446099
TI  - Canine vaccination.
AB  - New technologies for vaccine development and infectious disease diagnosis are
      likely to be introduced in the near future. With this new technology comes the
      opportunity to vaccinate companion animals against even more infectious agents
      than is currently practiced in the United States. As we look forward, it becomes
      particularly important to review current vaccination standards applied to dogs
      with respect to current knowledge of duration of immunity, awareness of
      incidence, and likelihood of injurious or even fatal adverse events associated
      with vaccination, and individual risk factors that dictate which vaccines are
      most appropriate at which stage of life.

PMID- 11446100
TI  - Vaccine-associated adverse events.
AB  - Although vaccination plays a vital role in maintaining animal health, there are
      risks associated with this medical procedure. Veterinarians are beginning to
      reexamine dogmatic vaccine protocols and consider both risks and benefits of
      vaccination, with special emphasis on adverse event information generated by
      practitioner experience. The current status of postmarketing surveillance for
      commercially available veterinary vaccines is presented, along with a discussion
      of the strengths and limitations of surveillance programs. An overview of adverse
      events commonly reported by veterinarians is included, along with practical
      information on how veterinarians can share their observations and learn about
      adverse events reported by their colleagues.

PMID- 11446101
TI  - The potential for liability in the use and misuse of veterinary vaccines.
AB  - The lack of specific rules regarding the use of animal vaccines by veterinarians
      leaves them vulnerable to legal action for negligence or breach of warranty. A
      veterinarian's liability may depend on the answers to the questions asked
      previously in this article. The answers ultimately depend on the specific
      circumstances of the case. Although no one can ensure that he or she is never
      going to be sued, veterinarians can go a long way in defending themselves against
      these kinds of allegations by conforming to the standards of practice as they
      apply to the care and use of vaccines; by adhering closely to the doctrines of
      informed consent; and by not providing undue warranty to the vaccine product he
      or she sells.

PMID- 11446102
TI  - Recombinant vaccine technology in veterinary medicine.
AB  - Recombinant technology is relatively new to veterinary medicine. It combines
      safety, purity, potency, and efficacy in the vaccine. Its positive features
      include not exposing the vaccinate to the pathogen, the lack of need for
      adjuvants, and stability that allows some vaccine to remain viable at ambient
      temperatures. These recombinants can receive multiple genetic inserts and present
      an opportunity to have multiple combination vaccines for use in animals. Licensed
      recombinant vaccines in veterinary medicine include those protecting against Lyme
      disease, pseudorabies, rabies, canine distemper, Newcastle disease, and a strain
      of avian influenza.

PMID- 11446103
TI  - What you can and cannot learn from reading a vaccine label.
AB  - Although most veterinarians look at vaccine labels each day, they rarely see
      them. When practitioners sense a need to read labels, they find that the labeling
      answers some of their basic questions but that these labels often fail to address
      many relevant issues. In addition, veterinarians find that the issues addressed
      are often presented simplistically and that the labels are sometimes just wrong.
      This article addresses what practitioners need to do to better understand the
      products most of them use on a daily basis.

PMID- 11446104
TI  - Rabies postexposure prophylaxis. Human and domestic animal considerations.
AB  - The emphasis on rabies control and prevention in the United States seems to be a
      function of our perception of proximity of the threat. Wildlife rabies epizootics
      within a state may be of little concern to the uninformed urban dweller.
      Additionally, many parts of the western United States are free of terrestrial
      rabies; were it not for the presence of bat rabies, people in those areas would
      likely interpret rabies control as a minor public health concern. It is essential
      that federal, state, and local public health programs emphasize the importance of
      rabies control through activities that include rabies education, sponsorship of
      legislated requirements for domestic animal vaccination, support for local animal
      control programs, and the promotion of recommendations that encourage the
      appropriate use of PEP. We are almost guaranteed that rabies is going to remain a
      major public health issue well into the next century because of expanding
      wildlife rabies epizootics, identification of new rabies viral variants with
      increased public health concern, emotional and legal concerns associated with
      rabies exposure, and increasing national cost associated with rabies control and
      prevention. Nevertheless, the development of new laboratory technology that
      allows an understanding of the epidemiologic nature of the rabies virus based on
      an evolving genetic history and the interrelationship with wildlife reservoirs
      should allow access to valuable tools for rabies control. When combined with
      programs using new developments in oral rabies vaccine that can immunize whole
      populations of wildlife reservoirs, that technology offers encouragement in our
      effort to control one of the diseases of antiquity.

PMID- 11446105
TI  - Importation of dogs and cats to rabies-free areas of the world.
AB  - Public pressure from a very mobile society has caused the governments of many
      rabies-free areas to reevaluate lengthy quarantine systems. In some areas a
      policy of vaccination, certification, and rabies antibody testing have been
      implemented to reduce the length of time a dog or cat must spend in quarantine.
      This has caused an increasing need for pet owners and veterinarians to understand
      quarantine regulations and shipping methods.

PMID- 11446106
TI  - Quantitative genetic variations and essential hypertension.

PMID- 11446107
TI  - Leptin and the regulation of body weight.

PMID- 11446108
TI  - The mouse as a gene discovery tool in the modern genome era.

PMID- 11446109
TI  - Programmed cell death and the regulation of homeostasis.

PMID- 11446110
TI  - From reverse transcriptase to gene therapy: a marvelous journey.

PMID- 11446111
TI  - Transcriptional control of Drosophila embryogenesis.

PMID- 11446112
TI  - Sex and death of a worm: assessing and repressing X chromosomes.

PMID- 11446113
TI  - Developments in radioecology in the new millennium.

PMID- 11446114
TI  - A critical review of measures to reduce radioactive doses from drinking water and
      consumption of freshwater foodstuffs.
AB  - Following a radioactive fallout event, there are a number of possible
      intervention measures to reduce radioactive doses to the public via the surface
      water pathway. We have critically reviewed the options available to decision
      makers in the event of radioactive contamination of surface waters. We believe
      that the most effective and viable measures to reduce radioactivity in drinking
      water are those which operate at the water treatment and distribution stage.
      Intervention measures to reduce concentrations of radioactivity in rivers and
      reservoirs are expected to be much less viable and efficient at reducing doses
      via the drinking water pathway. Bans on consumption of freshwater fish can be
      effective, but there are few viable measures to reduce radioactivity in fish
      prior to the preparation stage. Lake liming and biomanipulation have been found
      to be ineffective for radiocaesium, although the addition of potassium to
      lakewaters appears promising in some situations. Lake liming may be effective in
      reducing radiostrontium in fish, though this has not, to our knowledge, been
      tested. De-boning fish contaminated by strontium is probably the most effective
      food preparation measure, but salting and freezing can also reduce radiocaesium
      concentrations in fish. The provision of accurate information to the public is
      highlighted as a key element of countermeasure implementation.

PMID- 11446115
TI  - Countermeasures for animal products: a review of effectiveness and potential
      usefulness after an accident.
AB  - Over the last decade, there has been considerable progress in the development of
      countermeasures for preventing or reducing contamination of animal products by
      radioisotopes of iodine, caesium and strontium. In this paper, recent significant
      technical improvements are summarised and the current availability of
      countermeasures and their usefulness in the event of a nuclear accident reviewed.
      An improved understanding of factors controlling the metabolism of radioiodine
      and radiostrontium has enabled previously suggested countermeasures to be either
      optimised or dismissed. For radiocaesium in particular, experience since the
      Chernobyl accident has enabled effective and feasible countermeasures to be
      identified and successfully implemented in different situations. It has also been
      more widely understood that countermeasure effectiveness, although important, is
      not the only criterion which needs to be determined. In addition, cost and
      practical considerations such as availability, technical feasibility,
      acceptability and side-effects need to be taken into account. Evaluation of these
      factors has shown that some previously recommended countermeasures are unlikely
      to be feasible.

PMID- 11446116
TI  - Soil- and plant-based countermeasures to reduce 137Cs and 90Sr uptake by grasses
      in natural meadows: the REDUP project.
AB  - The effectiveness of a set of soil- and plant-based countermeasures to reduce
      137Cs and 90Sr transfer to plants was tested in natural meadows in the area
      affected by Chernobyl fallout. Countermeasures comprised the use of agricultural
      practices (disking + ploughing, liming and NPK fertilisation), addition of soil
      amendments and reseeding with a selection of grass species. Disking + ploughing
      was the most effective treatment, whereas the K fertiliser doses applied were
      insufficient to produce a significant increase in K concentration in soil
      solution. The application of some agricultural practices was economically
      justifiable for scenarios with a high initial transfer, such as 137Cs
      contaminated organic soils. The use of soil amendments did not lead to a further
      decrease in transfer. Laboratory experiments demonstrated that this was because
      of their low radionuclide sorption properties. Finally, experiments examining the
      effect of plant species on radionuclide transfer showed that both transfer and
      biomass can depend on the plant species, indicating that those with high
      radionuclide root uptake should be avoided when reseeding after ploughing.

PMID- 11446117
TI  - Short rotation coppice for revaluation of contaminated land.
AB  - When dealing with large-scale environmental contamination, as following the
      Chernobyl accident, changed land use such that the products of the land are
      radiologically acceptable and sustain an economic return from the land is a
      potentially sustainable remediation option. In this paper, willow short rotation
      coppice (SRC) is evaluated on radiological, technical and economic grounds for W.
      European and Belarus site conditions. Radiocaesium uptake was studied in a newly
      established and existing SRC. Only for light-texture soils with low soil
      potassium should cultivation be restricted to soils with contamination levels
      below 100-370 kBq m-2 given the TFs on these soils (5 x 10(-4) and 2 x 10(-3) m2
      kg-1) and considering the Belarus exemption limit for firewood (740 Bq kg-1). In
      the case of high wood contamination levels (> 1000 Bq kg-1), power plant
      personnel working in the vicinity of ash conveyers should be subjected to
      radiation protection measures. For appropriate soil conditions, potential SRC
      yields are high. In Belarus, most soils are sandy with a low water retention, for
      which yield estimates are too low to make production profitable without
      irrigation. The economic viability should be thoroughly calculated for the
      prevailing conditions. In W. Europe, SRC production or conversion is not
      profitable without price incentives. For Belarus, the profitability of SRC on the
      production side largely depends on crop yield and price of the delivered bio
      fuel. Large-scale heat conversion systems seem the most profitable and revenue
      may be considerable. Electricity routes are usually unprofitable. It could be
      concluded that energy production from SRC is potentially a radiologically and
      economically sustainable land use option for contaminated agricultural land.

PMID- 11446118
TI  - A cost-benefit analysis of long-term management options for forests following
      contamination with 137Cs.
AB  - This paper provides a description of a cost-benefit analysis applied to determine
      the cost effectiveness, or otherwise, of nine management strategies potentially
      applicable to forests contaminated with 137Cs. The management strategies were
      considered singly and in a number of likely combinations. A management strategy
      was considered to be cost-effective if it resulted in a lower overall monetary
      detriment than was incurred if use of the contaminated forest was continued on a
      'business as usual' basis. Only the banning of mushroom collection and
      restriction of public access proved to be cost-effective management strategies on
      the basis of this definition. However, even these strategies only proved cost
      effective at high levels of 137Cs contamination, at which net savings in
      detriment in the form of public dose were achieved. Cost-effective savings of
      doses to forest workers were never achieved at any of the contamination levels
      considered in this study. It is suggested that novel alternative uses of
      contaminated forests are required which could provide added value to the standing
      crop in return for small increases in public and worker doses. One such use might
      be biofuel production.

PMID- 11446119
TI  - FORIA: Forest Impact Analysis. An interactive decision support software providing
      information on the secondary effects of radiological countermeasures applied in
      forests.
AB  - FORIA (Forest Impact Analysis) is a decision support software that provides a
      synthesis of published information pertaining to the application of radiological
      countermeasures in forests and the secondary impacts that may result from their
      application. By linking relevant key parameters describing the forest environment
      and its social and economic roles, with information on the effects of
      countermeasures on a range of forest features, the potential secondary impacts of
      the countermeasures are indicated. User inputs refine this generic system to
      reveal the potential secondary effects of selected countermeasures for specific
      forest scenarios. FORIA has an Eastern European focus but is applicable to all
      forest scenarios.

PMID- 11446120
TI  - Self-help countermeasure strategies for populations living within contaminated
      areas of Belarus, Russia and Ukraine.
AB  - Countermeasures have been effectively employed within intensive agricultural
      systems in areas of the Former Soviet Union (FSU) affected by the Chernobyl
      accident. However, ingestion doses continue to be elevated in some areas as a
      result of few foodstuffs which are collected from the wild or produced by the
      household. Forest fungi and berries, and milk from privately owned cattle are the
      most notable contributors to 137Cs intakes amongst these foodstuffs. In this
      paper we consider advice which would help affected populations to both understand
      the importance of these exposure routes and to reduce their exposure. In addition
      to the potential radiological benefits, self-help schemes are highly cost
      effective and likely to have a positive psychological influence on populations
      living within contaminated areas of the FSU. Evidence to suggest that the
      transfer of radiocaesium to cow milk is considerably higher in the FSU than
      within western Europe and North America is discussed.

PMID- 11446121
TI  - Practical improvement of the radiological quality of milk produced by peasant
      farmers in the territories of Belarus contaminated by the Chernobyl accident. The
      ETHOS project.
AB  - The Chernobyl post-accident situation has highlighted how the sudden emergence of
      persistent radioactive contamination in the environment is severely affecting the
      quality of life of the inhabitants in the concerned territories. The management
      of this situation is complex, mainly conditioned by the ability of the
      inhabitants themselves to be directly involved in the process of improving their
      living conditions. In this process, quality of life cannot be restricted solely
      to the dimension of radiological risk, but needs to encompass the diverse aspects
      of daily living, including the social, psychological, economic, political and
      ethical aspects. This paper presents the experience of the involvement of a group
      of peasant farmers from a village in the Republic of Belarus, in the process of
      improving the radiological quality of privately produced milk. This experience
      took place in the context of the ETHOS project, funded by the radiation
      protection research programme of the European Commission. The principal objective
      was to implement a complementary approach to the rehabilitation strategies
      adopted so far in the contaminated territories of the Republic of Belarus. This
      paper retraces the process of involvement of the inhabitants in a working group.
      It describes the characterisation of the situation by local actors, the opening
      of new possible actions to improve the radiological quality of milk at the
      individual level and the positive consequences at the scale of the village. The
      ETHOS project also illustrates how the scientific knowledge accumulated over many
      years since the Chernobyl accident in the field of radiation protection and
      radioecology can enter into local practices in the form of practical tools, which
      can be used by the population to produce significant improvements in the
      radiological situation.

PMID- 11446122
TI  - Evaluation and ranking of restoration strategies for radioactively contaminated
      sites.
AB  - An international project, whose aim was the development of a transparent and
      robust method for evaluating and ranking restoration strategies for radioactively
      contaminated sites (RESTRAT), was carried out under the Fourth Framework of the
      Nuclear Fission Safety Programme of the EU. The evaluation and ranking procedure
      used was based on the principles of justification and optimisation for radiation
      protection. A multi-attribute utility analysis was applied to allow for the
      inclusion of radiological health effects, economic costs and social factors.
      Values of these attributes were converted into utility values by applying linear
      utility functions and weighting factors, derived from scaling constants and
      expert judgement. The uncertainties and variabilities associated with these
      utility functions and weighting factors were dealt with by a probabilistic
      approach which utilised a Latin Hypercube Sampling technique. Potentially
      relevant restoration techniques were identified and their characteristics
      determined through a literature review. The methodology developed by this project
      has been illustrated by application to representative examples of different
      categories of contaminated sites; a waste disposal site, a uranium tailing site
      and a contaminated freshwater river.

PMID- 11446123
TI  - Remediation strategies for rural territories contaminated by the Chernobyl
      accident.
AB  - The objective of the present paper is to derive remediation strategies for rural
      settlements contaminated by the Chernobyl accident in which annual doses to a
      critical group still exceed 1 mSv. Extensive radioecological data have been
      collected for 70 contaminated settlements. A dose model based on these data
      resulted in estimates that are on average close to and a bit less than the
      official dose estimates ('catalogue doses') published by the responsible
      Ministries of Belarus, Russia and Ukraine. For eight remedial actions that can be
      applied on a large scale, effectiveness and costs have been assessed in light of
      their dependence on soil type, contamination level and on the degree of previous
      application of remedial actions. Remediation strategies were derived for each of
      the 70 settlements by choosing remedial actions with lowest costs per averted
      dose and with highest degree of acceptability among the farmers and local
      authorities until annual doses are assessed to fall below 1 mSv. The results were
      generalised to 11 contamination/internal-dose categories. The total numbers of
      rural inhabitants and privately owned cows in the three countries distributed
      over the categories were determined and predicted until the year 2015. Based on
      these data, costs and averted doses were derived for the whole affected
      population. The main results are (i) about 2000 Sv can be averted at relatively
      low costs, (ii) the emphasis on reducing external exposures should be increased,
      (iii) radical improvement of hay-land and meadows and application of Prussian
      blue to cows should be performed on a large scale if annual doses of 1 mSv are an
      aim to be achieved, (iv) additional remedial actions of importance are
      fertilising of potato fields, distribution of food monitors and restriction of
      mushroom consumption, and (v) for inhabitants of some settlements (in total about
      8600) annual doses cannot be reduced below 1 mSv by the remedial actions
      considered.

PMID- 11446124
TI  - One of the fundamental objectives in the field of radioecology.

PMID- 11446125
TI  - Important factors governing exposure of the population and countermeasure
      application in rural settlements of the Russian Federation in the long-term after
      the Chernobyl accident.
AB  - Rural settlements located in areas of the Russian Federation contaminated after
      the Chernobyl accident and exceeding an annual dose of 1 mSv a-1 have been
      classified according to 137Cs contamination density, internal dose and the
      neighbourhood of forests. It has been shown that, with the exception of the most
      contaminated areas, the internal doses decreased in accordance with a decline in
      137Cs availability for plant root uptake. An inverse tendency was observed in
      areas with 137Cs contamination above 555 kBq m-2 which can be explained by a
      reduction or even termination of countermeasure application and by an increasing
      consumption of forest products in areas where restrictive countermeasures are
      still implemented. Twenty-seven settlements have been studied to estimate the
      effectiveness of countermeasures applied previously and to identify the most
      important factors governing the radiation exposure to the population and its
      change with time. It has been shown that the effectiveness of countermeasures
      which resulted in a decrease of up to 40% of doses has a tendency to decline in
      the long term. The need for continuation of remediation in rural settlements was
      evaluated both for selected settlements and extrapolated to the whole
      contaminated area and it has been shown that the application of countermeasures
      will be of importance at least up to the year 2045. Rather high effectiveness in
      terms of internal dose reduction (factor of 2-2.5) of radical improvement
      (disking, ploughing and reseeding) and administration of Cs binders to animals
      (Ferrocyn) was demonstrated for the selected settlements. It could be
      demonstrated that for forest-remote settlements there is a linear dependence
      between internal dose normalised to the density of contamination and the
      proportion of peat soils around settlements. For near-forest settlements, this
      dependence was less pronounced which can be explained by the high contribution of
      forest food products to the internal dose. Milk is still the major dose-forming
      product in rural Russian settlements (its contribution to internal dose in forest
      remote settlements is above 70%); however, in near-forest settlements, the
      contribution of mushrooms to the internal dose is comparable to the contribution
      from milk.

PMID- 11446126
TI  - Assessing potential secondary effects of countermeasures in agricultural systems:
      a review.
AB  - Secondary effects are defined as any positive or negative impacts resulting from
      the application of countermeasures other than radiological benefits or direct
      costs. They are categorised into environmental, radioecological, economic and
      social effects. Impacts on the environment may include changes in water, air and
      soil pollution or in the conservation and amenity value of an area.
      Radioecological effects occur when the countermeasure unintentionally alters the
      behaviour of the target radionuclide or any other radionuclide present. Economic
      effects may range from changes in agricultural income to environmental costs
      (e.g. impact of soil erosion on fisheries). Social effects relate to the
      acceptability of countermeasures, for example in terms of consumer confidence and
      animal welfare. Recent research into the identification and assessment of
      secondary effects is summarised. Non-quantitative and quantitative approaches are
      explained and formal evaluation procedures involving decision matrices and
      decision support systems are introduced. Examples of recent experimental and
      modelling work focusing on radiocaesium are given for the following
      countermeasures: soil application of potassium, administration of AFCF to
      livestock and ploughing techniques.

PMID- 11446127
TI  - Analyzing differences in the costs of treatment across centers within economic
      evaluations.
AB  - OBJECTIVES: Assessments of health technologies increasingly include economic
      evaluations conducted alongside clinical trials. One particular concern with
      economic evaluations conducted alongside clinical trials is the generalizability
      of results from one setting to another. Much of the focus relating to this topic
      has been on the generalizability of results between countries. However, the
      characteristics of clinical trial design require further consideration of the
      generalizability of cost data between centers within a single country, which
      could be important in decisions about adoption of the new technology. METHODS: We
      used data from a multicenter clinical trial conducted in the United Kingdom to
      assess the degree of variation in costs between patients and between treatment
      centers and the determinants of the degree of such variation. RESULTS: The
      variation between patients was statistically significant for both the
      experimental and conventional treatments. However, the degree of variation
      between centers was only statistically significant for the experimental
      treatment. Such variation appeared to be a result of hospital practice, such as
      payment mechanisms for staff and provision of hostel accommodation, rather than
      variations in physical resource use or substantive differences in cost structure.
      CONCLUSIONS: Multicenter economic evaluations are necessary for determining the
      variations in hospital practice and characteristics that can in turn determine
      the generalizability of study results to other settings. Such analyses can
      identify issues that may be important in adopting a new health technology.
      Analysis is required of similar large multicenter trials to confirm these
      conclusions.

PMID- 11446128
TI  - False-negative results in screening programs. Medical, psychological, and other
      implications.
AB  - OBJECTIVES: Assessment of the appropriateness of screening programs involves
      consideration of the harms as well as the benefits. These harms include the risk
      of false-negative results, the consequences of which have remained
      underinvestigated. This paper reports the results of a systematic literature
      review that aimed to assess the medical psychological, economic, and legal
      consequences of false-negative results in national screening programs. METHODS:
      The review included a comprehensive literature search and contact with experts to
      identify relevant literature. Most studies that were identified presented only
      anecdotal evidence. However, thirteen studies presented quantitative information
      on medical consequences of false negatives, eight studies presented information
      on psychological consequences, and two studies presented information on economic
      consequences. RESULTS: The strength of evidence from most of the primary studies
      was low. There is some evidence, however, that false-negative results may have a
      large legal impact. There is also a consensus in the literature that false
      negatives may have a negative impact on public confidence on screening; evidence
      is however limited. CONCLUSIONS: False negatives are evident even in high-quality
      screening programs. They may have the potential to delay the detection of breast
      and cervical cancer, but there is little evidence to help in assessing their
      psychological consequences. They also may lead to legal action being taken by
      those affected and may reduce public confidence in screening. Their impact may be
      reduced by provision of full information to participants about the benefits and
      limitations of screening programs and by increasing public education on these
      issues.

PMID- 11446129
TI  - A randomized trial to measure the optimal role of the pharmacist in promoting
      evidence-based antibiotic use in acute care hospitals.
AB  - BACKGROUND: There is a considerable gap between randomized clinical trials and
      implementing the results into practice. This is particularly relevant in the use
      of broad-spectrum antibiotics in hospitals. Hospital pharmacists can be effective
      vehicles for bridging this gap and promoting evidence-based medicine. To
      determine the most effective way of using the pharmacist in this role, a
      prospective cefotaxime intervention study was conducted with randomization
      incorporated into the design as well as patient-related therapeutic outcomes.
      METHODS: A total of 323 patients who were prescribed cefotaxime were randomized
      into an intervention or nonintervention group where only the former was
      challenged by pharmacists for inappropriate cefotaxime usage relative to hospital
      guidelines. The primary outcome was the appropriateness of cefotaxime prescribing
      between groups. Logistic regression analysis was then used to identify factors
      that were associated with successful clinical response. RESULTS: Overall, 94% of
      orders in the intervention group met cefotaxime dosage criteria compared with 86%
      in the control group (p = .018). However, there was no impact with respect to
      promoting cefotaxime use for an appropriate indication (81% vs. 80%; p = .67).
      There was a trend for improved clinical outcomes in patients who received
      cefotaxime within hospital guidelines (OR = 1.73; p = .31). CONCLUSIONS: The
      pharmacist as a vehicle for promoting the appropriate use of broad-spectrum
      antibiotics in the acute care hospital setting can improve the dosing of such
      agents. However, several barriers to optimizing the impact of the pharmacist were
      implied by the data. Removing these barriers could increase the pharmacists'
      utility as an agent for improved patient care.

PMID- 11446130
TI  - Dialysis for end-stage renal disease. Determining a cost-effective approach.
AB  - OBJECTIVE: Renal replacement therapy (RRT) is essential for maintenance of life
      for those with end-stage renal disease. However, there remain many areas of
      uncertainty about which method of RRT should be chosen. This paper reports an
      economic model based on a systematic review that attempts to determine which
      method of dialysis, continuous ambulatory peritoneal dialysis (CAPD) or
      hemodialysis, a patient should have as the initial method of RRT. METHODS: A
      systematic review and a costing exercise carried out in a Scottish hospital were
      used to populate a Markov model. Scenario analysis was used to model plausible
      variations in variables included in the model. RESULTS: In 8 of the 16 scenarios
      developed hemodialysis dominated CAPD. In a further eight scenarios, the cost per
      life-year displayed considerable variability, ranging from between 5,000 Pounds
      to 51,000 Pounds. The higher costs per life-year were associated with minimum
      estimates of additional survival for a patient starting RRT on hospital
      hemodialysis. CONCLUSION: It may be more cost-effective to manage patients
      starting on RRT with hospital hemodialysis than CAPD. This has particular
      implications for the United Kingdom, given that up to 50% of new patients receive
      CAPD.

PMID- 11446131
TI  - Elements for assessment of telemedicine applications.
AB  - OBJECTIVES: As an initiative of the International Network of Agencies for Health
      Technology Assessment, an approach to assessment of telemedicine applications was
      prepared to assist decision makers who are considering introduction and use of
      this technology. METHODS: Review and commentary drawing on published assessment
      frameworks and reports of primary evaluations of telemedicine, with particular
      reference to experience in Finland and Canada. RESULTS: Elements of the approach
      included development of a business case (considering population and services,
      personnel and consumers, delivery arrangements, specifications and costs);
      subsequent evaluation of the telemedicine application; and follow-up (covering
      the domains of technical assessment, effectiveness, user assessment of the
      technology, costs of telemedicine, trials, economic evaluation methods, and
      sensitivity analysis). CONCLUSIONS: Decision makers should link introduction of
      new and often costly technology to appraisal of its feasibility, followed by
      evaluation of the application, including longer term consideration of its
      sustainability and impact on the healthcare system. As the effectiveness and
      efficiency of telemedicine applications will often be strongly influenced by
      local issues, results of assessments may not be generalizable.

PMID- 11446132
TI  - Factors affecting the utilization of systematic reviews. A study of public health
      decision makers.
AB  - OBJECTIVE: To determine the extent to which public health decision makers used
      five systematic reviews to make policy decisions, and to determine which
      characteristics predict their use. METHODS: This cross-sectional follow-up study
      of public health decision makers in Ontario collected primary data using a
      telephone survey and a short, self-administered organizational demographics
      questionnaire completed by the administrative assistant for each Medical Officer
      of Health. Independent variables included characteristics of the innovation,
      organization, environment, and individual. Data were entered into a computerized
      database developed specifically for this study, and multiple logistic regression
      analysis was conducted. RESULTS: The participation rate was very high, with 85%
      of public health units and 96% of available decision makers completing the
      survey. In addition, 63% of respondents stated they had used at least one of the
      systematic reviews in the previous 2 years to make a decision. The most important
      predictors of use were one's position, expecting to use a review in the future,
      and perceptions that the reviews were easy to use and that they overcame the
      barrier of limited critical appraisal skills. CONCLUSIONS: Utilization of the
      systematic reviews in Ontario was very high. The utilization rates found in this
      study were significantly higher than those reported in previous utilization
      studies. One's position was found to be the strongest predictor of use,
      identifying program managers and directors as the most appropriate audience for
      systematic reviews.

PMID- 11446133
TI  - Screening and clinical management of prostate cancer. A cross-national
      comparison.
AB  - OBJECTIVES: The objectives of the study were to identify the current standards of
      clinical practice regarding prostate cancer screening in western Europe, Canada,
      and the United States, and to highlight major characteristics of current prostate
      cancer screening programs or patterns of practice. METHODS: We performed a semi
      structured interview by means of a self-administered questionnaire sent by fax to
      26 institutes pertaining to the International Network of Agencies for Health
      Technology Assessment. RESULTS: None of the countries surveyed had a formal
      national screening policy. Despite that, all the countries answering the
      questionnaire had discretionary, public-financed screening practices. Moreover,
      some scientific and professional organizations recommended population screening
      for prostate cancer, and few of the surveyed countries offered it as experimental
      practice within a randomized controlled trial. Survey results showed variation
      regarding screening policies, in particular test of choice, age cut-off points,
      and treatment prescribed for positive test results. CONCLUSIONS: Despite the lack
      of conclusive evidence on the benefits of prostate cancer screening, the
      availability of simple and easy-to-administer tests has lead to an enormous
      variation on screening policies around the world. Practice variations also affect
      prostate cancer therapy.

PMID- 11446134
TI  - Nice lessons to be learned.
AB  - OBJECTIVES: This study examined users' perceptions of the role and value of the
      Scottish Health Purchasing Information Centre (SHPIC) from 1995 to 1998. METHODS:
      Questionnaires and interviews were used to gather data from Scottish GP
      fundholders and health board managers at two stages. RESULTS: Initially,
      purchasers sought help in identifying the most relevant information. By 1997,
      while some appreciated the clinical and cost-effectiveness information produced,
      others were critical of lack of timely production and apparent lack of
      cooperation between agencies. CONCLUSIONS: New U.K. agencies can learn from
      SHPIC's problems, specifically in producing clear, coordinated, timely,
      independent, and well-marketed information with implementation strategies. POLICY
      IMPLICATIONS: It is important to evaluate the impact of agencies to produce and
      disseminate evidence-based information, even if this has to be done pragmatically
      rather than as an outcomes-based assessment. Evidence from evaluations can inform
      direction and strategy for existing and new agencies.

PMID- 11446135
TI  - The practice of discounting in economic evaluations of healthcare interventions.
AB  - OBJECTIVES: Discounting of costs in health-related economic evaluation is
      generally regarded as uncontroversial, but there is disagreement about
      discounting health benefits. We sought to explore the current recommendations and
      practice in health economic evaluations with regard to discounting of costs and
      benefits. METHODS: Recommendations for best practice on discounting for health
      effects as set out by government agencies, regulatory bodies, learned journals,
      and leading health economics texts were surveyed. A review of a sample of primary
      literature on health economic evaluations was undertaken to ascertain the actual
      current practice on discounting health effects and costs. RESULTS: All of the
      official sources recommended a positive discount rate for both health effects and
      costs, and most recommended a specific rate (range, 1% to 8%). The most
      frequently specified rates were 3% and 5%. A total of 147 studies were reviewed;
      most of these used a discount rate for health of either 0% (n = 50) or 5% (n =
      67). Over 90% of studies used the same discount rate for both health and cost.
      While 28% used a zero rate for both health and cost, in 64% a nonzero rate was
      used for both. Studies where the health measure was in natural clinical units
      (direct) were significantly more likely to have a zero discount rate. CONCLUSION:
      The finding that 28% of studies did not discount costs or benefits is surprising
      and concerning. A lower likelihood of discounting for benefits when they are in
      natural units may indicate confusion regarding the rationale for discounting
      health effects.

PMID- 11446136
TI  - A logit model for the effect of telecardiology on acute newborn transfers.
AB  - The deregionalization of neonatal intensive care in the United States has shifted
      the site of care for many newborn infants away from academic medical centers
      where subspecialty support is available. OBJECTIVE: To investigate the effect of
      immediate echocardiogram interpretation via telemedicine on rates of neonatal
      transfer to academic medical centers. METHODS: A logit model was developed to
      predict the probability of transfer from two regional level 3 neonatal intensive
      care units to academic medical centers. One of these units implemented a
      telecardiology program and the other acted as a comparison institution with on
      site cardiology expertise. The telecardiology intervention began 18 months into
      the 36-month study period. SUBJECTS: Infants (n = 2,142) admitted to neonatal
      intensive care at either of the two institutions during calendar years 1994
      through 1996. RESULTS: A statistically significant reduction in the rate of
      transfer to academic medical centers was observed. Telecardiology was associated
      with a 58% reduction of such transfers (p = .001, 95% CI = 30%, 75%). No such
      reduction was noted at the comparison institution. It is estimated that
      approximately 30 transfers were eliminated during the study period, resulting in
      the elimination of approximately $150,000 in hospital charges. In addition, the
      infants that were transferred after the adoption of telemedicine were more often
      transferred to their telemedicine partner institution (p < .02).

PMID- 11446138
TI  - Autism and Lovaas treatment: a systematic review of effectiveness evidence.

PMID- 11446137
TI  - Triple-marker screening in British Columbia: current practice and future options.

PMID- 11446139
TI  - Dyspepsia: evidence-based methods in the diagnosis and treatment of dyspepsia.

PMID- 11446140
TI  - [Lactic acid polymer implants in the repair of traumatic defects of the orbital
      floor].
AB  - BACKGROUND: The criteria determining the choice of the technique used to repair
      traumatic orbital floor defects include the quality of the expected result,
      morbidity, ease of use and plasticity of the method, and its cost and
      availability. Among the different methods proposed, lactic acid polymer implants
      are particularly interesting. MATERIAL AND METHODS: Eighteen patients with an
      isolated blow-out fracture of the orbital floor were treated with a lactic acid
      polymer implant between 1995 and 1996. Ten of these patients were reviewed at 24
      to 43 months follow-up. RESULTS: The mean age of the patients was 35 years (20-52
      years). No residual diplopia was observed. None of the patients had an anomalous
      orbital volume or ocular dystopia. None of the implants migrated. One patient
      experienced episodes of palpebral inflammation that resolved spontaneously. The
      ten patients reviewed were satisfied with the outcome. DISCUSSION: The properties
      of lactic acid polymer implants facilitate their use, avoid morbidity and provide
      a quality result. This is the procedure of choice for repairing tissue loss of
      the orbital floor. It has several advantages over alternative methods (the
      implants are rigid, thin, resorbable and well tolerated) without having their
      defects (thickness, fragility, roughness, predetermined form, rapid alteration,
      specific instrumentation, iatrogenic disorders). In addition, lactic acid polymer
      plates can be remodeled when heated, allowing a precise adaptation of the implant
      to the orbital structures. Finally, the cost, compared with the advantages, is
      not a barrier for routine use.

PMID- 11446141
TI  - [Chondrosarcoma of the jaw. A case localized to the mandible].
AB  - Chondrosarcoma is a malignant cartilaginous tumor rarely found in the jaw bone.
      Tumor progression is slow with strong propensity to local recurrence after
      surgical removal. The prognosis is poor and depends on the degree of
      differentiation and the quality of the resection. We report a case of mandibular
      chondrosarcoma that exhibited particularly massive extension to soft tissue. We
      discuss the epidemiology, diagnosis, treatment and follow-up of these tumors.

PMID- 11446142
TI  - [Mucoepidermoid carcinoma appearing synchronously in the lacrimal and salivary
      glands].
AB  - An 86-year-old woman consulted for a swelling on the palpebral side of the upper
      eyelid that she had discovered 4 months earlier. Physical examination also
      revealed a parotid nodule on the same side. Clinical and radiological findings
      were in favor of a malignant lacrimal tumor. The parotid localization would
      correspond to either a lymph node metastasis or an intraparotid metastasis or to
      a primary parotid tumor with salivary metastasis; We discuss these hypotheses in
      light of the epidemiology, history and clinical and pathology findings.

PMID- 11446143
TI  - [Primary hyperparathyroidism presenting as a brown tumor of the maxilla and hard
      palate. Apropos of a case].
AB  - Significant controversy persists in the classification of giant cell lesions of
      the maxillofacial skeleton. Multifocal giant cell lesions are strongly suggestive
      of hyperparathyroidism brown tumors. Maxillary localization is extremely rare. We
      report a case of primary hyperparathyroidism manifesting in the form of giant
      cell tumors of the maxilla, the hard palate and long bones. Biochemistry
      confirmed the diagnosis. Computed tomography localized the parathyroid tumor at
      the cervicothoracic junction in the retrosternal area. We discuss the clinical
      features of skeletal involvement in primary hyperparathyroidism and stress the
      need for ionized serum calcium assay in case of giant cell tumors of the cranial
      bones.

PMID- 11446144
TI  - [Gunshot wounds to the face. A proposed classification].

PMID- 11446145
TI  - [Precancerous lesions of the buccal mucosa].
AB  - OBJECTIVES: We analyzed data in the literature in comparison with experience at
      the Department of Cancer and Oral pathology of the Stomatology and Maxillo-Facial
      Surgery division of la Salpetriere Hospital on precancerous lesions of the oral
      mucosa, in order to establish definitions and describe epidemiological, clinical,
      histological findings as well as natural history and treatment outcome. MATERIAL
      AND METHODS: Three literature sources were analyzed: Medline and Current Contents
      searches, books and references listed in articles. The following key words were
      used and classed into three groups; 1) oral mucosa, epidemiology, precancerous
      lesions, malignant transformation, dysplasia, leucoplakia, oral lichen planus,
      erythroplasia, verrucous, cheilitis, candidosis, immunodepression, 2) oral
      mucosa, tumor markers, carcinogens, keratin, keratinocytes, gene, nuclear
      proteins, p53 protein, Ki-67 antigen, 3) oral mucosa, therapy, prevention,
      nutrients. The period chosen ran from 1980 to 1998. This automatic literature
      search was completed by systematic manual search of summaries in specialized
      journals published in 1997-1998. The lists of references in the identified
      articles were consulted and furnished the principal publications concerning
      precancerous lesions of the buccal mucosa. In all 383 references were selected
      and analyzed by level of scientific proof. Among these 135 are cited in the text.
      If data in the literature were insufficient, the physicians at the Department of
      Cancer and Oral pathology of the Stomatology and Maxillo-Facial Surgery division
      of La Salpetriere Hospital were consulted to provide their experience-based
      recommendations. RESULTS AND DISCUSSION: Clear and practical definitions drawn
      from current knowledge were adopted. Precancerous lesions were distinguished from
      precancerous states. Precancerous lesions included chronic lesions of the oral
      cavity on which cancer of the oral cavity is known to develop. These were:
      leucoplakia, oral lichen planus, erythroplasia, papillomatous lesions, actinic
      cheilitis, submucosal fibrosis, keratotic candidosis, and tertiary syphilis. The
      precancerous states included cancers occasionally observed in the oral cavity:
      immunodepression and Plummer Vinson syndrome were analyzed. Epidemiological,
      clinical, histological, and evolutive data as well as therapeutic strategies were
      described. A decisional algorithm was elaborated for leucoplakia. The text was
      enriched with images available in the Department. CONCLUSION: Precancerous
      lesions of the oral mucosa offer a particularly interesting area of research for
      understanding the process of cancer formation and its prevention. The level of
      scientific proof available in the large majority of the published reports is low.
      Few recent publications provide relevant data. In practice, the experience in the
      management of cancer and precancerous lesions of the oral mucosa accumulated over
      the last 40 years at the Department of Cancer and Oral pathology of the
      Stomatology and Maxillo-Facial Surgery division of la Salpetriere Hospital
      provides an invaluable source of information.

PMID- 11446146
TI  - The concept of attributable risk in epidemiology: yesterday, today and tomorrow.

PMID- 11446147
TI  - Attributable fractions: fundamental concepts and their visualization.
AB  - A general methodology for visualizing attributable fractions in epidemiology is
      described. The methodology applies to the multifactorial exposure situation and
      embraces various types of attributable fractions including adjusted, sequential
      and average attributable fractions. The concept of the scaled Venn diagram plays
      a central role, illustrating total disease risk and excess disease risk
      attributable to the exposures as areas in a unit square. This forms the ground
      for making simple pie charts of attributable fractions summing to 1 (or 100%).
      The potential applications extend from cohort and cross-sectional data to data
      from case-control studies. The methodology is illustrated by theoretical as well
      as empirical examples including the risk of motor fatalities attributable to
      driver's blood alcohol concentration and age, and the prevalence of chronic cough
      attributable to smoking habits, occupational exposure to dust or gas, and
      residence. A total of 40 figures illustrate the methodology.

PMID- 11446148
TI  - A review of adjusted estimators of attributable risk.
AB  - This paper reviews adjusted methods of estimation of attributable risk (AR), that
      is methods that allow one to obtain estimates of AR while controlling for other
      factors. Estimability and basic principles of AR estimation are first considered
      and the rationale for adjusted AR estimators is discussed. Then, adjusted AR
      estimators are reviewed focusing on cross-sectional, cohort and case-control
      studies. Two inconsistent adjusted estimators are briefly commented upon. Next,
      adjusted estimators based on stratification, namely the weighted-sum and Mantel
      Haenszel (MH) approaches, are reviewed and contrasted. It appears that the
      weighted-sum approach, which allows for full interaction between exposure and
      adjustment factors, can be affected by small-sample bias. By contrast, the MH
      approach, which rests on the assumption of no interaction between exposure and
      adjustment factors may be misleading if interaction between exposure and
      adjustment factors is present. Model-based adjusted estimators represent a more
      general and flexible approach that includes both stratification approaches as
      special cases and offers intermediate options. Bruzzi et al.'s and Greenland and
      Drescher's estimators are reviewed and contrasted. Finally, special problems of
      adjusted estimation are considered, namely estimation from case-cohort data,
      estimation for risk factors with multiple levels, for multiple risk factors, for
      recurrent events, estimation of the prevented and preventable fractions, and
      estimation of the generalized impact fraction. Comments on future directions are
      presented.

PMID- 11446149
TI  - Partitioning methods for multifactorial risk attribution.
AB  - The epidemiological problem of risk attribution in the framework of multiple
      exposures has been the subject of intensive research activities in the last
      decade. In particular, partitioning methods have been developed to define new
      multidimensional measures of attributable risk putting the task of quantifying a
      proportion of disease events in a population that can be ascribed to the adverse
      health effects of certain risk factors into a multifactorial perspective. The
      parameters generalize the concept of attributable risk to different
      multifactorial frameworks in which multiple exposures might be arranged in
      hierarchically ordered classes or in equally ranking groups. Partitioning methods
      are reviewed and differences between the multifactorial variants of attributable
      risk are illustrated by a component causes model.

PMID- 11446150
TI  - The application of methods to quantify attributable risk in medical practice.
AB  - Several epidemiological parameters have been introduced for quantifying the
      population impact of a certain exposure on morbidity on a population level,
      termed 'attributable risk' (AR). Of these definitions, the AR as suggested by
      Levin in 1953 or some algebraic transformations of it are most commonly used. A
      structured literature search, based on the Medline database, identified 334
      original epidemiological studies dealing with this AR published between 1966 and
      1996 (mostly case-control studies). A considerable increase in the number of
      published studies incorporating some quantification of the exposure impact on the
      population level in terms of the AR was observed in the last decade. However, in
      64.5% of these studies no exact definition of the AR used was given. Adjustment
      procedures necessary in multifactorial situations were performed by only 37.5%,
      confidence intervals for the AR were given by only 19.3% of authors. Thus,
      although the increasing popularity of this important epidemiological measure is
      encouraging, its correct application and comprehensive reporting in medical
      practice should be promoted further.

PMID- 11446151
TI  - Predictors, prodromes and incidence of postpartum depression.
AB  - The purpose of this study was to determine the incidence of clinically
      significant depression occurring between 1 and 4 months postpartum and to
      investigate whether somatic complaints, subsyndromal depressive symptoms, or
      birth-related concerns among non-depressed women at 1 month were predictive of
      postpartum depression. This is a prospective cohort study of 465 women from the
      Wisconsin Maternity Leave and Health Project (WMLHP). Women who were not
      depressed at 1 month postpartum were reassessed 3 months later for depression
      occurring at any time in the interval between 1 and 4 months postpartum.
      Depression was defined as either meeting the criteria for major depression on the
      National Institute of Mental Health (NIMH) Diagnostic interview Schedule (DIS) or
      scoring above 15 on the Center for Epidemiologic Studies Depression Scale (CES
      D). Physical symptoms were assessed by an adapted Health Responses Scale. Other
      measures were developed specifically for the WMLHP. Of 465 women, 27 (5.8%)
      became clinically depressed between 1 and 4 months postpartum. In a logistic
      regression analysis, four variables (maternal age, depression during pregnancy,
      thoughts of death and dying at 1 month postpartum, and difficulty falling asleep
      at 1 month postpartum) were predictive of depression at 4 months postpartum.
      Breast-feeding, mode of delivery, family income, parity and mother's education
      did not predict depression. The existence of subsyndromal depressive symptoms,
      particularly thoughts of death and dying, may represent a prodromal phase of
      depression and should alert clinicians to the possibility of future postpartum
      depression. Women with a history of depression during pregnancy should be
      monitored for signs of postpartum depression for a minimum of 4 months.
      Obstetricians are in a unique position during the postpartum check-up to screen
      women for these predictors of future postpartum depression and possibly to avert
      the development of a clinically significant depressive episode.

PMID- 11446152
TI  - Women with Turner syndrome: psychological well-being, self-rated health and
      social life.
AB  - Psychological well-being, self-rated health and social situation were
      investigated in a cross-sectional multidisciplinary study of 63 women with Turner
      syndrome (TS; mean age 31.5 years, range 18-59 years). The psychological
      examination included a semi-structured interview, and use of two standardized
      self-rating scales, the Psychological General Well-being Index (PGWB) and the
      Nottingham Health Profile (NHP). Psychological well-being and self-rated health
      were similar in the women with TS and Swedish female normative data, matched for
      age. However, the women with TS reported more social isolation than the normative
      group. Within the TS group, the oldest women reported more psychological distress
      and poorer health than the youngest. Those with impaired self-rated health
      reported more emotional distress. The women with TS were studying or in
      employment to the same degree as the general population, although fewer were
      cohabiting. In the interview, both negative and positive consequences of TS were
      reported. This study did not find any evidence for impaired psychological well
      being, although it did indicate that women with TS experience more difficulties
      in the area of social and partner relationships.

PMID- 11446153
TI  - Early menopause?

PMID- 11446154
TI  - Quality assessment and quality control in psychosomatic obstetrics and
      gynecology: old wine in new bottles?

PMID- 11446155
TI  - 'Animal electricity'.

PMID- 11446156
TI  - Cyclical mastalgia: prevalence and associated health and behavioral factors.
AB  - Perimenstrual breast pain (cyclical mastalgia) is a common problem that can be
      sufficiently severe to interfere with usual activities, and has been associated
      with elevated mammography usage in young women. This study was undertaken to
      replicate clinic-based research on cyclical mastalgia, and to examine the
      association between this disorder and health-related behaviors and perceived
      stress. Using random digit dialing throughout Virginia, 874 women aged 18-44 were
      interviewed. Sixty-eight per cent of women experienced cyclical breast symptoms;
      22% experienced moderate to extreme discomfort (classified as cyclical
      mastalgia). Hormonal contraceptive usage was associated with significantly less
      mastalgia and premenstrual syndrome (PMS). Smoking, caffeine consumption and
      perceived stress were associated with mastalgia (odds ratios = 1.52, 1.53 and
      1.7, respectively). Young women (under 35 years) with mastalgia were more likely
      to have had a mammogram (20.2%) than those without mastalgia (9.9%). Most women
      with this disorder (77.5%) did not have PMS. The prevalence of cyclical mastalgia
      and its association with mammography replicate clinic-based findings.
      Associations with smoking and stress had not previously been reported.
      Prospective research is needed to determine the biopsychosocial factors
      contributing to this disorder.

PMID- 11446157
TI  - The management of eating disorders in a fertility clinic: clinical guidelines.
AB  - Although the wish for a child may be ambivalent in women with anorexia or bulimia
      nervosa, the prevalence of eating disorders in fertility clinics is probably
      underestimated. Motivated by the wish for a child, these couples may be reluctant
      to reveal a history of an eating disorder and/or show resistance to some therapy
      for this disorder. Nevertheless, in our opinion, the eating disorder must be in
      full remission before any fertility treatment can start, if treatment is still
      necessary at that moment. Illustrated with some case examples, we will discuss
      the major problems and clinical strategies in the management of these complex
      cases, based upon the experience in our own fertility clinic.

PMID- 11446158
TI  - Sexuality, partner relations and contraceptive practice after termination of
      pregnancy.
AB  - The aim of this study was to determine the impact of termination of pregnancy
      (TOP) on women's sexual well-being, the couple and contraceptive practice. In a
      prospective qualitative and quantitative study, 103 women undergoing induced
      abortion by vacuum aspiration were interviewed before the abortion and 6 months
      later. The interview was performed by means of a questionnaire including open and
      closed questions, and two psychological tests (Locke-Wallace and Horowitz). After
      TOP, the majority of women did not report changes in their sexual behavior and
      satisfaction. Eighteen per cent of women reported a decrease in sexual desire and
      17% reported orgasmic disorders. About one-third of women described psychosomatic
      symptoms, but a minority were traumatized by the event. Ninety-eight per cent of
      the women were informed about, and had practiced, contraception in the past; 69%
      had actually used some kind of contraception during the menstrual cycle that had
      resulted in pregnancy (31% had had unprotected intercourse). Six months later,
      83% practiced contraception, and only 17% did not. Fourteen out of 84 couples
      separated after TOP (one in six). Six months after TOP, the large majority of
      women interviewed seemed able to cope with TOP. A minority presented some
      persisting sexual dysfunction and/or some psychosomatic symptoms.

PMID- 11446159
TI  - Assessing psychopathology in pregnancy and postpartum.
AB  - This paper evaluates questionnaire measures of anxiety, depression and
      posttraumatic stress disorder for use with pregnant and postpartum women. For
      each area of measurement the main issues or problems are delineated, two
      appropriate measures are described and the validity and reliability of the
      measures are discussed, as well as the problems and benefits of using the
      measures with pregnant or postpartum women. Finally, norms are provided for
      female and obstetric samples, where available. It is hoped that this paper will
      provide a valuable resource for future research into psychopathology in pregnant
      and postpartum women.

PMID- 11446160
TI  - Molecular modelling of 17 alpha-hydroxylase-17,20-lyase.
AB  - New methods in treatment of hormone-dependent diseases like prostate or breast
      cancer have become a major subject in medical and pharmaceutical research.
      Because of the direct correlation of cancer growth and hormone concentration
      inhibition of hormone biosynthesis reveals a promising strategy in cancer
      therapy. The key enzyme of androgen biosynthesis is the cytochrome P450 system 17
      alpha-hydroxylase-17,20-lyase. To gain deeper insights into the structure and
      function of this enzyme, whose crystal structure is still unknown we present in
      this paper a theoretical 3D-model of the human 17 alpha-hydroxylase-17,20-lyase.
      The model was built by homology modelling using the crystal structure of the P450
      CYPeryF as a template. After energy minimisation followed by molecular dynamics
      simulation the refined model exhibits reasonable protein geometry and a good
      protein folding quality. For evaluation of protein stability the structure was
      subjected to molecular dynamics in a waterbox under almost physiological
      conditions using the GROMACS program. The protein structure and folding remains
      stable even after 300 ps of free molecular dynamics simulation. The calculation
      of interaction fields employing the program GRID was used to characterise the
      active site of the protein. Subsequent docking studies with the natural substrate
      pregnenolone and further molecular dynamics of the protein-substrate-complexes
      enabled us to propose a putative binding-site for the physiological substrates.

PMID- 11446161
TI  - Structure-activity relationships of novel anti-malarial agents: 1. arylacyl and
      cyclohexylacyl derivatives of 5-amino-2-tolylacetylaminobenzophenone.
AB  - We have identified compound 1 as a lead structure of a novel class of anti
      malarial agents. Here, we report on our continuing studies towards the
      establishment of structure-activity relationships by varying the terminal phenyl
      moiety and the alkyl linker of the acyl substituent at the 5-amino function of
      the benzophenone core structure. Most of the derivatives of our lead structure 1
      essentially display the same anti-plasmodial activity as the lead.

PMID- 11446162
TI  - [Isochromanes related to fluoxetine].
AB  - The structure of fluoxetin (1) led to the substituted 3'-phenyl-1'-isochromanyl-2
      ethylamines 4-9. These are synthesized by ring closure of the 1,2
      diphenylethanols 2a-c with 3-chloropropanal-diethylacetal/BF3-etherate and
      reaction of the chlorides 3a-c with amines. The affinities to the 5-HT2A-receptor
      and the serotonin transporter are tested.

PMID- 11446163
TI  - [Ring cleavage of N-arylpyridinium salts by nucleophiles--regioselectivity and
      stereochemistry of the products. 2].
AB  - The reaction of quaternary 3-pyridinecarboxamide compounds 2, 7 and 14 with
      alkali does not--contrary to literature--result in regiospecific ring opening,
      but yields mixtures of position isomer penta-2,4-dienal derivatives. With
      increasing steric hindrance by the 3-substituent, the hydroxide ion prefers the
      attack at 6-position. Usually products with all trans configuration are obtained.
      Only the 2-substituted aldehydes from 2 and 14 additionally occur in the 2,3-cis
      configuration as 5b and 21b, explainable by a hydrogen bond between the formyl
      and carbamoyl group. Surprisingly the "ring opened" 5-aminopenta-2,4-dienals 5
      and 6 resp. 21 and 22 in acetone solution show an equilibrium of the positional
      isomers in each case, which must be generated by recyclization via the
      intermediates 24 resp. 25. With hydroxylamine 2, 7 and 14 only react to the 4
      substituted pentadienal derivatives, which represent E,Z oxime mixtures. This is
      proved by dehydration to uniform nitriles and the synthesis from the
      corresponding aldehydes by oximation.

PMID- 11446164
TI  - [Identity and physicochemical properties of 1-(4-chlorophenyl)-4-morpholino
      imidazolin-2-one, AWD 131-138].
AB  - The structure of the anticonvulsant 1-(4-chlorophenyl)-4-(4-morpholinyl)-2,5
      dihydro-1H-imidazolin-2-one (Code: AWD 131-138, CAS-No.: 188116-07-6) was proved
      by IR, UV, 1H NMR, 13C NMR and mass spectra. AWD 131-138 is practically insoluble
      in a neutral aqueous medium at 20 degrees C (S approximately 0.08 g/l). The
      solubility of the substance in 0.1 N HCl is about 2.7 g/l. In DMF, AWD 131-138 is
      sparingly soluble (S approximately 28.5 g/l). The pKa-value is about 2.5. The
      partition coefficients P = COctanol/Cwater at 37 degrees C range from 0.7 at pH
      approximately 1 to about 20 at pH > or = 6.

PMID- 11446165
TI  - Determination of histamine in trypsine by capillary zone electrophoresis--a
      possible alternative to the bioassay?
AB  - A rapid capillary electrophoresis separation was developed in order to separate
      histamine from trypsine. A calibration curve with a determination limit of 1.0
      microgram/ml histamine in 1 mg/ml trypsine was obtained. The method is suitable
      for the detection of small amounts of histamine contamination in trypsine with
      regard to the standards of the European Pharmacopoeia.

PMID- 11446166
TI  - Flavonoid content assay: influence of the reagent concentration and reaction time
      on the spectrophotometric behavior of the aluminium chloride--flavonoid complex.
AB  - The spectrophotometric assay based on aluminum chloride complex formation is one
      of the most commonly analytical procedures applied to flavonoid content
      determination. However, only a few optimization studies on the reaction
      conditions were done so far. The present work aims to the investigation of
      aluminum chloride concentration and reaction time effects on the
      spectrophotometric behavior of different flavonoids. The effects of both
      variation factors were studied by Central Composite Design and Response Surface
      Analysis methodology. The absorption data analysis showed that the effects of
      reaction time and reagent concentration on the absorption maximum are intricate
      and specific. A clear relationship between spectrophotometric behavior and
      flavonoid type or particular structure patterns could not be established.

PMID- 11446167
TI  - Pharmacokinetics of morphine 3-esters after oral administration in rabbits.
AB  - Pharmacokinetics of three morphine 3-esters-3-(2,2-dimethylvaleroyl) morphine
      (A), 3-(2-phenylbenzoyl) morphine (B), and 3-(2,2-diphenylpropionyl) morphine (C)
      was characterized after single oral administration in rabbits. Blood was sampled
      up to 24 h and cerebro-spinal fluid (CSF) was collected with the last blood
      sample. The concentration of the morphine 3-esters, morphine, morphine 3
      glucuronide and morphine 6-glucuronide were determined in plasma and CSF using
      HPLC UV-detection. The morphine 3-esters were suggested to be a subject to marked
      presystemic elimination, since, in comparison to the administration of the un
      esterified morphine, relatively low concentrations of morphine and morphine
      glucuronides were detected in plasma. The rate of disposition of morphine was
      dependent on the hydrolytic stability of the esters. The mean (+/- S.E.) plasma
      half-life of morphine was 0.9 +/- 0.2 h, 2.5 +/- 0.6 h and 3.5 +/- 3.5 h after
      the administration of A, B and C, respectively, compared to 0.9 +/- 0.2 h as
      estimated after the administration of non-esterified morphine. An analgesic
      effect will be achieved, since morphine was detected in CSF even 24 h after the
      application of the ester pro-drugs. It is concluded that esterification at the 3
      position may be adapted to obtain sustained plasma levels of morphine.

PMID- 11446168
TI  - X-ray diffraction, differential scanning calorimetry and thermogravimetry
      combined with infrared analysis of freeze-dried prednisolone hemisuccinate.
AB  - In this study, the thermal behaviour of freeze-dried prednisolone hemisuccinate
      (Prednisolut) was investigated by means of X-ray scattering, differential
      scanning calorimetry (DSC) and fourier transformation infra-red analysis (FT-IR).

PMID- 11446169
TI  - Control and stability of drug release from diffusion pellets coated with the
      aqueous quaternary polymethacrylate dispersion Eudragit RS 30 D.
AB  - The addition within compatibility limits of the pore formers hydroxypropyl
      methylcellulose (HPMC) and hydroxy ethylcellulose (HEC) to coatings of the
      quaternary polymethacrylate dispersion Eudragit RS 30 D enables drug release to
      be controlled without problems. 20 and 15%, respectively, of these pore formers
      are suitable for release within 8 h of theophylline from pellets with a coating
      thickness of about 30 microns. A 10% addition of plasticizer, water soluble
      triethyl citrate (TEC) or water insoluble dibutyl phthalate (DBP), lowers the
      minimum film forming temperature (MFT) from 48 to 17 and 26 degrees C,
      respectively. The MFT is scarcely influenced by the pore formers. However, the
      plasticizers may modify the effect of the pore formers: HPMC is more effective in
      the presence of DBP. In spite of the preparation of the coatings at a bed
      temperature about 20 degrees C above MFT, the release from the diffusion pellets
      is not stable during storage. Only curing in an oven or in the fluidized bed up
      to a certain limiting release rate at 80 degrees C for 1 h results in stable
      products. Increased relative humidity allows reduction of the curing temperature.
      The water soluble additives polyoxy ethylene (PEG) and polyvinyl pyrrolidone
      (PVP) and insoluble additives are ineffective as pore formers.

PMID- 11446170
TI  - Preparation factors affecting the properties of polylactide nanoparticles: a
      factorial design study.
AB  - PLGA nanoparticles were produced using a w/o/w emulsification solvent evaporation
      method incorporating pilocarpine HCl as a model drug. The influence of four
      preparation parameters on the particle properties was studied. The factors
      studied were the concentration of the stabilizer in the outer water phase, the
      presence of buffer in the outer water phase, the amount of drug relative to the
      amount of polymer and the type of PLGA used. Particle size was influenced by the
      concentration of PVA in and the addition of buffer to the outer water phase. The
      ratio drug/polymer had an effect on the drug entrapment.

PMID- 11446171
TI  - Differentiation between inducers of apoptosis and nonspecific cytotoxic drugs by
      means of cell analyzer and immunoassay.
AB  - Differentiation between specific and nonspecific cytotoxic drugs by means of cell
      analyzer and immunoassay is described. The determination of antiproliferative,
      cytotoxic, and apoptotic effects as well as enlargement of cells in response to
      toxic compounds can be used for the disclosure of compounds with a specific mode
      of action. The usefulness of the procedure was demonstrated with camptothecin (1)
      as a cytotoxic drug and established inducer of apoptosis. Aphidicolin (2) and the
      new compound oxoaphidicolin (3) were shown to display no comparable effect.
      Isolation and structural data of 3 are reported.

PMID- 11446172
TI  - Azidothymidine induces dose dependent increase in micronuclei formation in
      cultured HeLa cells.
AB  - Exposure of HeLa cells to azidothymidine (AZT) resulted in a concentration
      dependent decline in growth kinetics. 100 microM of AZT completely inhibited the
      cell growth. The frequency of binucleate and multinucleate cells declined with
      increasing concentration of AZT and the formation of multinucleate cells was
      completely inhibited at 20 and 30 h at higher concentrations indicating
      inhibition of cell division. Similarly, the clonogenicity of cells declined in a
      concentration dependent manner and 10 microM AZT killed 50% of the cells.
      Conversely, the frequency of MNBNC (micronucleated binucleate cell) increased in
      a concentration dependent manner and was significantly higher in the AZT treated
      group than the non-drug treated control group. The relationship between
      concentrations of AZT and micronuclei-induction was linear for all the post
      treatment time periods studied. The biological response was also determined by
      plotting the surviving fraction of cells on the X-axis and the number of
      micronuclei on the Y-axis. A close and inverse correlation between the surviving
      fraction and micronuclei formation was observed and the data could be fitted on
      to a linear quadratic model.

PMID- 11446173
TI  - Comparison of pharmacophore cinnoline and quinoline systems on the basis of
      computer calculation and pharmacological screening of their condensed systems.
AB  - A series of new pyrimido[5,4-c]quinoline derivatives were prepared to compare the
      pharmacophore systems of cinnoline and quinoline. These compounds were obtained
      by the cyclocondensation of appropriately substituted 4-amino-3
      quinolinecarboxylic acids 3 with acetic anhydride to the respective 2-methyl-1,3
      oxazino[5,4-c]quinolin-4(3 H)-ones 4. These derivatives reacted with amines and
      gave N-3 substituted 2-methylpyrimido[5,4-c]quinolin-4(3 H)-ones 6. 4-Amino-3
      quinolinecarboxamide 2 reacted with diethyl carbonate to give 1,2,3,4
      tetrahydropyrimido[5,4-c]quinolin-2,4-diones 5. The SAR parameters of the
      derivatives obtained were analysed with the HyperChem 5.1/ChemPlus 2.0 computer
      program. The compounds synthesized were screened for their effect on the CNS.

PMID- 11446174
TI  - The effects of aqueous extracts of Desmodium gangeticum DC. (Leguminosae) on the
      central nervous system.
AB  - The aqueous extract of Desmodium gangeticum DC. (Leguminosae) showed no analgesic
      activity in the hot plate method, but it showed severe anti-writhing activity in
      the acetic acid-induced abdominal writhing assay. It exhibited moderate central
      nervous system depressant activity in the spontaneous motor activity, hole cross,
      and open field tests and hole board tests. The effects of this extract on
      locomotion were compared with some standard CNS drugs.

PMID- 11446175
TI  - Procyanidins from the herb of Hypericum perforatum.
AB  - From the aqueous acetone extract of the herb of Hypericum perforatum the
      flavanols catechin (1) and epicatechin (2), and the procyanidins A2 (9), B1 (3),
      B2 (4), B3 (5), B5 (6), B7 (7) and C1 (8) were isolated. Their structures were
      established as their peracetate derivatives, on the basis of chemical and
      spectral evidence. The 13C NMR spectrum of the higher molecular weight polymer
      fraction revealed a 3',4'-dihydroxylated B-ring oxidation pattern and the 2,3-cis
      relative stereochemistry of the constituent flavan-3-ol units. The mean average
      molecular size of the polymers was estimated to be 4 to 5 flavan-3-ol units. The
      procyanidin pattern in comparison to that of Crataegus spec. is briefly
      discussed.

PMID- 11446176
TI  - [Functional foods and pediatric nutrition].

PMID- 11446177
TI  - [Chronic recurrent multifocal osteomyelitis in children: report of 17 cases].
AB  - Chronic recurrent multifocal osteitis (OCRM) is a rare condition in children, of
      unknown aetiology, which may be misdiagnosed as osteomyelitis, arthritis or
      tumour. PATIENTS AND METHODS: We present a retrospective multicentric study of 17
      patients (five boys and 12 girls) with an average follow-up of 7.5 years (six
      months-25 years). RESULTS: A spectrum of presenting features is possible, ranging
      from bone lesions alone to lesions combined with arthritis, palmoplantar
      pustulosis or psoriasis. The diagnosis was delayed from two weeks to five years.
      Roentgenographic evaluation was often normal at the beginning of the disease or
      showed nonspecific bone reactions. Radioisotope bone scans assisted in
      establishing the diagnosis and in identifying lesions that were initially
      clinically silent. Bone biopsies were performed in seven cases. Histopathological
      examination showed only mild inflammatory nonspecific changes. Microbiological
      cultures were always negative. Treatments were different according to the
      evolution of the disease and the hospital. There was no response to antibiotics
      in seven patients. The response to nonsteroidal anti-inflammatory agents and
      steroids was moderate and often transient. Salazopyrine and pamidronate treatment
      used in two patients allowed a durable remission. We lost sight of four patients,
      pain persisted in three in spite of treatment, it disappeared in two with
      treatment, mild pain persisted in five without treatment and remission occurred
      in three without treatment. CONCLUSION: This study clarifies the clinical and
      radiologic features of chronic recurrent multifocal osteomyelitis. The
      recognition of this rare entity is often delayed and difficulties in patient
      management sometimes emerge from its usual protracted course.

PMID- 11446178
TI  - [Laparoscopic splenectomy in children: experience and results].
AB  - Pediatric laparoscopic splenectomy is a relatively new surgical procedure.
      Advances in instrumentation and technique now make this procedure possible.
      Splenectomy is frequently performed in children for various hematologic and
      autoimmune diseases. PATIENTS AND METHODS: This article reviews the indication
      for splenectomy, the technique of laparoscopic splenectomy and our results.
      Between January 1996 and January 2000, 23 children underwent laparoscopic
      splenectomy. Three of them also had a concomitant cholecystectomy. Their ages
      ranged from three to 14 years. Nine children had hereditary spherocytosis, four
      were affected by sickle cell disease, three had an idiopathic thrombocytopenia
      and three a hemolytic disease. One patient was converted. RESULTS: Mean operative
      time was 170 min (range, 115-230 min). Hospital stay ranged from three to 15 days
      (median, 6). Five patients had complications (three pneumonia and two deep
      abscesses). Median follow-up was 20 months (two months to four years) without
      problems regarding procedure. CONCLUSION: Regarding the low complication rate for
      this type of patient and the advantages of a small abdominal trauma in the
      postoperative period, the laparoscopic approach for elective splenectomy in
      hematological disorders is the technique of choice.

PMID- 11446179
TI  - [Health checkup for 3- to 4-year-old children: results of screening tests
      performed in 1999 by physicians in the Maternal and Infant Welfare program in the
      Gironde region].
AB  - BACKGROUND: In the Gironde region, the physicians of the Mother and Infant
      Welfare department in charge of the 3- to 4-year-old childrens' health checkup
      have set up a public health approach which led to new practical methods of
      screening tests in 1999. These have been used to evaluate the children's health
      problems of that age group in the region. POPULATION AND METHODS: This study
      concerned 12,421 children born in 1995, attending the nursery schools of Gironde,
      who underwent a health checkup (visual and hearing screening test, language and
      behaviour exploration) in 1999. RESULTS: Among them, 5,208 children failed
      screenings. One child out of six had language disorders, one child out of seven
      presented amblyopia, one out of eight suffered from behavioral problems and one
      child out of nine from a hearing defect. Furthermore, one out of three children
      who failed the test had several problems. CONCLUSION: This study has enabled us
      to objectify the frequency of the troubles and their association, this
      information being particularly useful for evaluating these children's health
      needs and to help improve their healthcare management.

PMID- 11446180
TI  - [Method for using inhalation chambers with facial masks in asthma. Evaluation in
      60 children below four years of age].
AB  - Spacers with face masks are widely used for the treatment of asthma in young
      children. A poor inhalation technique may compromise the treatments efficiency.
      METHODS: The inhalation technique of spacers with face masks was evaluated in a
      prospective study of 60 children below four years of age. A checklist of 12 items
      was used, each one being coded by zero or one, and a total score < or = 12 points
      was calculated. RESULTS: Mean total score was 8.93 +/- 1.84 (extremes: 6-12). The
      canister was shaken before use in 48.3% of cases, one puff delivered when the
      child was breathing in 71.7% and the valve's mobility checked in 85%. The
      canister was shaken before the second puff in 13.3% of cases and two consecutive
      puffs individualized in 28%. DISCUSSION: The usual mistakes are lacking to shake
      the canister and consecutive puffs' individualization. Medical partners and
      families education should be reinforced.

PMID- 11446181
TI  - [Papular filariasis].
AB  - 'River blindness' is the main problem of onchocerciasis. Despite a high
      prevalence of onchocerciasis in endemic countries, cases of imported cutaneous or
      ocular onchocerciasis in France are rare. CASE REPORT: We report the case of a
      chronic papular onchodermatitis with voluminous lymphadenopathy in a Cameroonian
      child, resolving with a treatment of ivermectin. CONCLUSION: The main symptom of
      cutaneous onchocerciasis is pruritus, which symptom may alert physicians when
      dealing with patients who come from endemic countries for onchocerciasis.
      Cutaneous aspects may vary depending on length of exposure to antigens and immune
      responses by the host against microfilariae. Nowadays, onchocerciasis is treated
      with a single dose of ivermectin, which is sufficient for eye and cutaneous
      symptoms. However, this therapy is efficient only against microfilariae, and
      treatments have to be repeated many times to avoid relapses linked to persistence
      of adult worms.

PMID- 11446182
TI  - [Paraplegia and medullary arteriovenous malformation. Role of surgery,
      corticosteroids and embolization].
AB  - CASE REPORT: We report the case of a nine-year-old child with a cervical
      medullary arteriovenous malformation (AVM), revealed by total paraplegia, whose
      regression started during steroid therapy, before embolization. CONCLUSION: The
      frequency of AVM's spontaneous favorable outcome is unknown but should not be
      underestimated. It might be improved by steroids.

PMID- 11446183
TI  - [Kikuchi-Fujimato disease].
AB  - Chronic adenopathies usually reveal lymphoma or infectious disease, particularly
      tuberculosis. CASE REPORT: We report a case of Kikuchi-Fujimato's disease
      revealed by cervical adenopathies, associated with fever and inflammatory
      syndrome. CONCLUSION: The diagnosis of Kikuchi-Fujimato's disease lies on
      histological examination. Resolution is faster with steroids.

PMID- 11446184
TI  - [Hodgkin's disease limited to intrathoracic sites. Case report].
AB  - Hodgkin's disease without peripheral lymphadenopathy or hepatosplenomegaly is
      exceptional. CASE REPORT: Hodgkin's disease was revealed by lung nodules, one of
      them cavitating, with mediastinal enlargement. Diagnosis was confirmed on a video
      assisted pleuroscopic biopsy. CONCLUSION: Hodgkin's disease should be considered
      in case of mediastinal enlargement with lung nodules.

PMID- 11446185
TI  - [French pediatric oncology: analysis of the present situation and future
      prospects].
AB  - In France, the cure rate of paediatric malignancies is presently above 70%. The
      main contributing factors of the major improvement in the management of
      paediatric malignancies in recent years have been the development of a
      multicentric national and international clinical research, and the setting up of
      a network of multidisciplinary teams covering the whole country and working with
      technology transfer laboratories. The French group of study of cancers and
      leukemias in childhood works on the structuring of the French paediatric oncology
      on the three following themes: 1) the definition of the criteria required to be
      recognised as a reference centre in paediatric oncology; 2) the training of the
      future paediatricians specialised in haematology and oncology; and 3) the
      modalities of development and financial support of the clinical research. This
      paper mainly concerns the first point. Based on a national questionnaire survey,
      the measures needed to improve the organisation of the paediatric
      hyperspecialties are presented.

PMID- 11446186
TI  - [IgA deficiency].
AB  - Selective IgA deficiency is the most common primary immunodeficiency, with a
      prevalence of approximately 1/600 in whites. Most subjects are asymptomatic but
      some may suffer from frequent respiratory and gastrointestinal infections.
      Patients who suffer from frequent infections usually have a defect in antibody
      responses toward polysaccharides, which is often associated with IgG2 deficiency.
      Genetic predisposition to develop IgA deficiency has been shown to be linked to
      at least one locus on 6p21. Some IgA-deficient patients are also prone to develop
      more severe immunodeficiency called common variable immunodeficiency, which is
      associated with decreased IgG and sometimes IgM production as well as partial T
      cell defect. In a few cases, IgA deficiency may reveal a severe disease such as
      ataxia-telangiectasia. Selective IgA deficiency contraindicates immunoglobulin
      administration. Only the minority of IgA-deficient patients who develop severe or
      frequent infections in association with IgG2 deficiency or impaired antibody
      response are candidates for prophylactic intravenous immunoglobulin substitution.
      Immunoglobulin preparations containing particularly low amounts of IgA are
      required to avoid adverse effects related to anti-IgA alloantibodies.

PMID- 11446187
TI  - [Need for revision to the December 20, 1988 law relative to the protection of
      persons participating in biomedical research (Huriet's law)].
AB  - In France, biomedical research is governed by the law on the protection of people
      who participate in biomedical research passed on December 20, 1988. Considering
      that this law is becoming an obstacle to some useful investigations, 50
      scientific societies, organizations, and patients associations have written a
      memorandum asking for its revision. This memorandum contains propositions for
      alleged procedures while preserving the welfare of people who participate in
      biomedical research.

PMID- 11446188
TI  - [Cognitive-behavioral management of sleep disorders in young children].
AB  - Sleep disorders are prevalent in young children, the most frequent being
      disturbances in initiating and maintaining sleep. Behavioral and cognitive
      approaches are interesting techniques for their management. They can be used
      either for solving sleep problems at home, or in severe forms as part of a
      'deconditioning' during a short hospitalization.

PMID- 11446189
TI  - [Fluoride and children].
AB  - Fluoride is considered as an essential carioprophylactic agent. However, its use
      raises problems related to the possible negative effects of excessive intake.
      Precautions are therefore necessary when prescribing fluoride to children. This
      includes: 1) evaluation of all sources of fluoride for each individual child and
      his/her family; 2) evaluation of the cariogenic risk for the child according to
      his/her environment; and 3) estimation of the family's ability to follow medical
      advice and prescriptions. The role of the practitioner is thus to adapt the
      fluoride prescription according to the age and particular cariogenic
      susceptibility of each child. Pediatricians, general practitioners and dentists
      need to be convinced of how important regular visits to the dentist are for all
      children, from an early age. Not only fluoride, but also nutrition and hygiene
      are essential factors in achieving good dental health in childhood.

PMID- 11446190
TI  - [When to consult an orthodontist?].
AB  - Orthodontics aims to improve face and teeth harmony and to allow a good
      development of orofacial and occlusive functions. Orthodontic treatment is
      adapted to each individual case and may be early or late. Orthodontic indications
      and management require a collaboration between the paediatrician, the dentist and
      the orthodontist. The main indications are described.

PMID- 11446191
TI  - [Report of a rare immunodeficiency, JAK-3 protein deficiency].

PMID- 11446192
TI  - [Grunting in Senegalese children: a symptom predictive of death or serious
      illness].

PMID- 11446193
TI  - [An avoidable metabolic risk of treatment with growth hormone].

PMID- 11446194
TI  - [Accidental ingestion of a button battery].

PMID- 11446195
TI  - [Pasteurella multocida meningitis in a newborn].

PMID- 11446196
TI  - [Adrenal insufficiency as the only manifestation of X-linked
      adrenoleukodystrophy].

PMID- 11446197
TI  - Gay and bisexual adolescent boys' sexual experiences with men: an empirical
      examination of psychological correlates in a nonclinical sample.
AB  - Over the last quarter century the incest model, with its image of helpless
      victims exploited and traumatized by powerful perpetrators, has come to dominate
      perceptions of virtually all forms of adult-minor sex. Thus, even willing sexual
      relations between gay or bisexual adolescent boys and adult men, which differ
      from father-daughter incest in many important ways, are generally seen by the lay
      public and professionals as traumatizing and psychologically injurious. This
      study assessed this common perception by examining a nonclinical, mostly college
      sample of gay and bisexual men. Of the 129 men in the study, 26 were identified
      as having had age-discrepant sexual relations (ADSRs) as adolescents between 12
      and 17 years of age with adult males. Men with ADSR experiences were as well
      adjusted as controls in terms of self-esteem and having achieved a positive
      sexual identity. Reactions to the ADSRs were predominantly positive, and most
      ADSRs were willingly engaged in. Younger adolescents were just as willing and
      reacted at least as positively as older adolescents. Data on sexual identity
      development indicated that ADSRs played no role in creating same-sex sexual
      interests, contrary to the "seduction" hypothesis. Findings were inconsistent
      with the incest model. The incest model has come to act as a procrustean bed,
      narrowly dictating how adult-minor sexual relations quite different from incest
      are perceived.

PMID- 11446198
TI  - Sexual dysfunction: a neglected complication of panic disorder and social phobia.
AB  - Little is known about sexual dysfunctions comorbid with anxiety disorder. The aim
      of this study is to evaluate retrospectively the sexual function of social phobic
      patients in comparison with a panic disorder sample. Using a semistructured
      interview (SCID-I), 30 patients with social phobia and 28 patients with panic
      disorder were examined. The DSM-IV criteria were employed to diagnose sexual
      dysfunctions in this sample; however, the "C" criterion, which states that "the
      sexual dysfunction cannot be related to other Axis I disorders," was excluded.
      Panic disorder patients reported a significantly greater proportion of sexual
      disorders compared with social phobics: 75% (21/28) vs. 33.3% (10/30) (p =
      .0034). Sexual aversion disorder was the most common sexual dysfunction in both
      male (35.7%; 5/14) and female (50%; 7/14) panic disorder patients, and premature
      ejaculation was the most common sexual dysfunction in male social phobic
      patients: 47.4% (9/19). These results suggest that sexual dysfunctions are
      frequent and neglected complications of social phobia and panic disorder.

PMID- 11446199
TI  - Comparison of men's and women's attempts to dissuade sexual partners from the
      couple using condoms.
AB  - Undergraduate students were asked about their use of condoms and their attempts
      to dissuade sexual partners from the couple using condoms during sexual
      intercourse. Nearly 14% of women and nearly 17% of men who had engaged in sexual
      intercourse admitted to having actively tried to dissuade a partner from the
      couple using condoms. Thirty percent of the men and 41% of the women said that a
      sexual partner had tried to dissuade them. Attempts to dissuade partners from the
      couple using condoms were most common among students who reported having 10 or
      more lifetime sexual partners. For both men and women, the most frequently
      employed categories of verbal strategies were (1) sex feels better without a
      condom, (2) will not get pregnant, and (3) will not get a sexually transmitted
      disease. These three categories accounted for about three-fourths of the lines
      used. Avoidance of condoms because of a perceived decrease in physical pleasure
      poses a particular problem for sex and health educators.

PMID- 11446200
TI  - Sexual and emotional variables influencing sexual response to erotica: a
      psychophysiological investigation.
AB  - The relative contribution of attentional and emotional factors to the
      physiological and subjective sexual arousal elicited by erotic film was
      evaluated. Sexual arousal, attentional, and emotional responses were measured
      while 30 men were presented with a series of erotic film segments. Levels of
      physiological and subjective sexual arousal were higher when subjects became
      absorbed in the activities portrayed in the film and when they experienced the
      depicted erotic encounters as appetitive, than when they were distracted and
      perceived the encounters as aversive. The erotic film elicited a diminished
      startle response to a sudden burst of white noise presented during stimulation
      relative to the nature film, suggesting that at a physiological level the erotic
      segments of film were processed as more appetitive in valence. The level of
      sexual arousal elicited by the erotic segments was related to the extent to which
      subjects were entertained by the film, even though there was considerable anxiety
      generated by the portrayed sexual scenarios. Sexual response was not
      significantly correlated with trait measures of absorption (as indexed by the
      Tellegen Absorption Scale) nor with vividness of imagery (as assessed by the
      Betts Questionnaire upon Mental Imagery). Arousal was related to state-assessed
      attentional and emotional variables, and physiological measures of emotional
      response, demonstrating the multidimensional nature of the sexual response.
      Future directions for comparing male sexual response patterns with female
      response patterns are suggested.

PMID- 11446201
TI  - Depot-leuprolide acetate for treatment of paraphilias: a report of twelve cases.
AB  - A new class of antiandrogen medications, gonadotropin-releasing hormone agonists,
      offers promise in the treatment of the paraphilias, with substantially less side
      effects than medroxyprogesterone acetate or cyproterone acetate. This paper
      reports the results of treatment using a depot suspension of leuprolide acetate
      on 12 patients with paraphilic disorders or with sexual disorders not otherwise
      specified to suppress or help these individuals control their deviant sexual
      behavior or impulses. The method involved uncontrolled observations of
      individuals treated with depot-leuprolide acetate for various lengths of time,
      from 6 months to 5 years, with the follow-up intervals ranging from 6 months to 6
      years. Leuprolide acetate resulted in a significant suppression of deviant sexual
      interests and behavior as measured by self-report and was well tolerated.
      However, the three patients who were on long-term therapy developed bone
      demineralization, suggesting that this is a significant side effect of prolonged
      therapy. Leuprolide acetate shows promise as a treatment for the paraphilias.

PMID- 11446202
TI  - Parental selection of children's sexual orientation.
AB  - As we learn more about the causes of sexual orientation, the likelihood increases
      that parents will one day be able to select the orientation of their children.
      This possibility (at least that of selecting for heterosexuality) has generated a
      great deal of concern among supporters of homosexual rights, with such selection
      being widely condemned as harmful and morally repugnant. Notwithstanding this
      widespread condemnation, and even assuming, as we do, that homosexuality is
      entirely acceptable morally, allowing parents, by means morally unproblematic in
      themselves, to select for heterosexuality would be morally acceptable. This is
      because allowing parents to select their children's sexual orientation would
      further parent's freedom to raise the sort of children they wish to raise and
      because selection for heterosexuality may benefit parents and children and is
      unlikely to cause significant harm.

PMID- 11446203
TI  - Bem, Daryl J., Exotic becomes erotic: interpreting the biological correlates of
      sexual orientation, Archives of Sexual Behavior Vol. 29, No. 6, December 2000.

PMID- 11446205
TI  - Biomedical signals databases.

PMID- 11446204
TI  - What is life?
AB  - Life is a composite process in nature that is as fundamental as the laws of
      physics that govern the behavior of the inanimate world. The laws of physics
      change qualitatively as we go from the macroscopic to the atomic and subatomic
      domains. Likewise, the behavior of living systems changes dramatically when a
      certain level of complexity, including social organization, has been reached.
      Moreover, live systems may change the projected course of the inanimate world, as
      they are already doing on our tiny planet. In brief, life does not only "make the
      world turn around," it can do this for the whole universe. Consequently, life is
      probably the most significant process in nature; it is also the least
      predictable. The behavior of live systems is unpredictable. Unlike the inanimate
      universe that can be readily modeled using a limited number of parameters, the
      perpetually increasing complexity of living systems defies modeling. If we would
      have used all the information available about the behavior of live systems on
      this planet just five million years ago, we could never have come up with a model
      describing human civilization of today. Such a prediction would have been,
      obviously, much harder if we knew everything about living systems on this planet
      five hundred million years ago. The nonpredictability of the behavior of living
      systems is not solely due to its stochastic nature. The behavior of live systems
      is unpredictable because it is based on interactions among millions of
      independent or partially dependent stochastic processes involving both live and
      inanimate systems. The number of different pathways constituting such behavior is
      virtually infinite. This makes the predictability of such behavior qualitatively
      different from that of conventional stochastic behavior, which is based on a
      finite number of parameters, each with a finite number of degrees of freedom.
      Furthermore, unlike statistical mechanics, which are applicable to inanimate
      systems, the behavior of living systems cannot be delimited by an analog to
      Heisenberg's uncertainty principle. The answer to the question "What is life?"
      is, in brief: Life is a multifunctional process in nature that is as fundamental
      as the basic "laws" of physics, used to model the behavior of the inanimate
      world. Like those "laws," life can control the behavior of our universe,
      including its lifespan.

PMID- 11446206
TI  - Acquisition of biomedical signals databases.

PMID- 11446207
TI  - Standards for biomedical signal databases.

PMID- 11446208
TI  - Web-based acquisition, storage, and retrieval of biomedical signals.

PMID- 11446209
TI  - The impact of the MIT-BIH arrhythmia database.

PMID- 11446210
TI  - The SIESTA project polygraphic and clinical database.

PMID- 11446211
TI  - The challenges in creating critical-care databases.

PMID- 11446212
TI  - The European Neurological Network database and sleep atlas.

PMID- 11446213
TI  - PhysioNet: a Web-based resource for the study of physiologic signals.

PMID- 11446214
TI  - Database design for an archive of animal sounds.

PMID- 11446215
TI  - Toward a global bat-signal database.
AB  - We propose a scheme for a new database using standardized protocol for recording
      and analysis of bat calls. The proposed database will describe and archive
      echolocation signals to create a reference library of bat calls. This information
      should be accessible to the public, thus encouraging continuous feedback from a
      broad audience. Because it is essential to evaluate the quality and reliability
      of such data, detailed information of recording and analysis procedures as well
      as the resulting species identification is required. A standardized and growing
      database on bat calls would be a potentially invaluable tool for global species
      identification, comparison, and distribution of microchiropterans. Currently,
      apart from a few websites with local call libraries, there is no "global"
      database established yet. We hope that researchers, amateurs, and wildlife and
      management authorities will adopt and further modify our suggestions for a
      standardized database for bat calls. We also hope that this database will
      stimulate new directions in bat research.

PMID- 11446216
TI  - Cell-cell interactions in inflammation and cancer metastasis.

PMID- 11446217
TI  - The Hofgeismar lectures: a contemporary overview of Horneyan psychoanalysis.
AB  - Part I of this paper describes Karen Horney's theory of neurosis. In the 1930s,
      Horney repudiated Freud's view of female developmental psychology. She argued
      that cultural factors rather than anatomy or innate biological drives were the
      primary determinants not only of female development but of personality, as well.
      When genetic and environmental circumstances together lead to basic anxiety early
      in life, she believed a deep inner conflict emerges in the individual leading to
      the need for elaborating layers of rigidified protective defenses. She called
      this the neurotic process. This process can result in discrete symptoms of mental
      disorder as well as the more generalized problems of alienation from the person's
      real self and reliance on neurotic solutions. In Part II, the practical
      application of Horney's theory to clinical work is demonstrated in a case
      presentation of a notably timid and perfectionistic man. Part III points up
      elaborations of Horney's theories by later workers of her school, the American
      Institute for Psychoanalysis, and provides a history of her school within the
      broader context of American psychoanalysis. The author's emphasis on postmodern
      and narrativist elements of Horneyan psychoanalysis are illuminated, as well.

PMID- 11446218
TI  - Why do people stay in hateful relationships? The concept of malignant
      vindictiveness.
AB  - Why do couples remain in hateful relationships? This article defines
      theoretically rigorous ways of viewing partners who stay together despite severe
      strife. A case presentation shows how a relationship of two people, each with his
      or her character structure and idealized image, creates interpersonal conflict
      because of opposing demands each makes on self and other. Such conflict requires
      radical defensive measures including alienation, idealization, and
      externalization that increase tensions. A vicious circle of malignant
      vindictiveness cements the relationship. Increasing implacability in the
      relationship is understood through Horneyan categories of interlocking idealized
      images, hurt pride reactions, and the externalizing process.

PMID- 11446219
TI  - Karen Horney: a bibliography of her writings.

PMID- 11446220
TI  - Ferenczi's "A Little Chanticleer": a child's favorite song recall.
AB  - In response to the recent special issue of The American Journal of Psychoanalysis
      dedicated to Sandor Ferenczi's works, this article highlights his essay entitled,
      "A Little Chanticleer" as a first-of-its-kind legacy of a description of
      conscious and unconscious dynamics linked to a child's musical preferences in
      daily life. In addition to its historical value, Ferenczi's essay merits study
      from contemporary viewpoints on infant developmental research, including
      implications for treatment of adults. It is hoped that at least in the context of
      song recall Ferenczi's essay will gain its due recognition.

PMID- 11446221
TI  - The psychotherapeutic encounter: sexual acting out as the focus of intervention.
AB  - Clinical observation indicates that sexual acting out takes place during periods
      in which the integrity of the self is threatened by some disappointment, some
      frustration, or what is perceived as an unavoidable but unfair demand. Rather
      than confront the problem within the object relationship, the conflict is acted
      out. The sexual encounter reduces anxiety and facilitates the containment of
      depressive and aggressive feelings. Self-integration is attempted even at the
      risk of losing something, be it a wife, a husband, a girlfriend or the
      presidency. At the time it seems the only possible way to cope with painful or
      threatening stimuli.

PMID- 11446222
TI  - Nationalism and patriotism: national identification and out-group rejection.
AB  - It is argued that the differentiation between nationalism and patriotism proposed
      in the literature can be seen as analogous to judgments based on different types
      of comparisons: intergroup comparisons with other nations are associated with
      intergroup behaviour that corresponds to nationalism, whereas temporal or
      standard comparisons are linked with behaviour that corresponds to patriotism.
      Four studies (N = 103, 107, 96 and 105) conducted in Germany and Britain examined
      the hypothesis that national identification and in-group evaluation only show a
      reliable relationship with out-group rejection under an intergroup comparison
      orientation. Participants were primed with either an intergroup comparison, a
      temporal comparison or no explicit comparison orientation. A subsequent
      questionnaire assessed in-group (own country) identification, in-group evaluation
      (i.e. national pride) and rejection of national out-groups. Across all four
      studies, both in-group identification and in-group evaluation show a stronger
      correlation with out-group derogation if participants were primed with an
      intergroup comparison orientation compared to temporal and control conditions.
      Results are discussed with regard to nationalism and patriotism as well as Hinkle
      and Brown's (1990) model on relational vs. autonomous orientations.

PMID- 11446223
TI  - Social Identity Theory does not maintain that identification produces bias, and
      self-categorization theory does not maintain that salience is identification: two
      comments on Mummendey, Klink and Brown.

PMID- 11446224
TI  - Nations and nationalisms: particular cases and impossible myths.

PMID- 11446225
TI  - National identity: pride and prejudice?

PMID- 11446226
TI  - A rejoinder to our critics and some of their misapprehensions.

PMID- 11446227
TI  - Predicting gender from electronic discourse.
AB  - There is substantial evidence of gender differences in face-to-face
      communication, and we suspect that similar differences are present in electronic
      communication. We designed three studies to examine gender-preferential language
      style in electronic discourse. In Expt 1, participants sent electronic messages
      to a designated 'netpal'. A discriminant analysis showed that it was possible to
      successfully classify the participants by gender with 91.4% accuracy. In Expts 2
      and 3, we wanted to determine whether readers of e-mails could accurately
      identify author gender. We gave participants a selection of messages from Expt 1
      and asked them to predict the author's gender. It was found that for 14 of the 16
      messages used, the gender of author was correctly predicted. In the third
      experiment, six messages about gender-neutral topics were composed. Using a
      subset of the variables identified in Expt 1, female and male versions of each
      message were created. When participants were asked to rate whether a female or a
      male wrote these messages, their ratings differed as a function of the message
      version. These findings establish that people use gender-preferential language in
      informal electronic discourse. Furthermore, readers of these messages can use
      these gender-linked language differences to identify the author's gender.

PMID- 11446228
TI  - Meaning-seeking in the illusory correlation paradigm: the active role of
      participants in the categorization process.
AB  - The present research examines the role of categorical perception (McGarty,
      Haslam, Turner, & Oakes, 1993) in the illusory correlation paradigm. This
      approach assumes that the search for meaningful differences between two stimulus
      groups can lead to the illusory correlation effect. This explanation is
      investigated in Study 1 by presenting participants with constrained stimulus
      information and examining whether accentuating evaluative differences between
      stimuli could provide a basis for illusory correlation. Results of this study (N
      = 64) revealed illusory correlation effects that were related to evaluative
      reinterpretations of the stimuli. Study 2 (N = 19) focused on the causal relation
      between illusory correlation and accentuation effects, using the thinking-aloud
      technique. Detailed analyses of each participants' behaviour indicated that
      illusory correlation can arise from actively seeking intergroup differences and
      that reinterpretations of stimuli and the perception of illusory correlation were
      mutually reinforcing. Implications of these results for stereotyping processes
      are discussed.

PMID- 11446229
TI  - Counterfactuals and motivation: mood as input to affective enjoyment and
      preparation.
AB  - Two studies demonstrated that moods, in interaction with motivational goals, can
      influence counterfactual thinking (mental simulations of 'what might have been').
      This was shown for performances on laboratory tasks (Study 1) and for real-life
      course exams (Study 2). In Study 1, with enjoyment goals, participants in good
      moods generated the greatest number of downward (worse than actuality)
      counterfactuals; with performance goals, participants in bad moods generated the
      greatest number of upward (better than actuality) counterfactuals. Downward
      counterfactuals in good moods with enjoyment goals was reflected in concern with
      affective motives, positive moods and low preparation. Upward counterfactuals in
      bad moods with performance goals was reflected in concern with preparative
      motives, negative moods and high preparation. In Study 2, affective and
      preparative goals were manipulated directly, mirroring Study 1. After success,
      participants with affective goals generated the greatest number of downward
      counterfactuals, which was reflected in high enjoyment, positive moods and low
      preparation. After failure, participants with preparative goals generated the
      greatest number of upward counterfactuals, which was reflected in concern with
      performance, negative moods and high preparation. Discussion centres on
      implications for counterfactuals, self-motives and mood-as-input research.

PMID- 11446230
TI  - 'Abnormalization' of ethnic minorities in conversation.
AB  - Social psychologists studying intergroup relations have shown a renewed interest
      in social norms. In doing so, norms are treated typically as a non-problematic
      given and independent of the actual practices people are involved in. This study
      examines the discursive construction and representation of abnormality by
      analysing discussions held by some ethnically Dutch inhabitants of old inner-city
      quarters in Rotterdam. It is shown how these people in focus-group type talk
      construct the behaviour of ethnic minority residents as 'abnormal' in a
      recognizable number of ways. They set the ethnic minority residents in contrast
      with 'obviously normal' practices; they use extreme case formulations in
      describing their behaviour; and they draw upon 'unarguable' human values in
      explaining their judgments. Further, specific versions of reality were
      constructed in providing a justificatory account of their assessment, and
      undermining cultural interpretations were managed by criticizing ethnic minority
      culture, questioning particular behaviour as an instance of culture, and arguing
      for the need for adaptation.

PMID- 11446231
TI  - The strategic confirmation of meta-stereotypes: how group members attempt to
      tailor an out-group's representation of themselves.
AB  - This article is concerned with the influence of the group membership of an
      audience on the description of the in-group. Negative meta-sterotypes (stereotype
      of the in-group believed to be held by members of a relevant out-group) have
      aversive consequences on the self (Vorauer, Main, & O'Connell, 1998). Group
      members may therefore try to modify the meta-sterotype to their advantage by
      confirming positive traits and disconfirming negative ones. Such a strategy is
      not relevant when one addresses in-group members because one does not expect them
      to adhere to the content of the meta-stereotype. The study varied the salience of
      the meta-stereotype orthogonally to the group membership of the audience (out
      group vs. in-group). Participants (N = 75) were asked to pick traits that applied
      to their group. As predicted, participants selected more positive traits
      belonging to the meta-stereotype and fewer negative ones when addressing out
      group members than in-group members, but this occurred only when the meta
      stereotype was salient. Both low and high identifiers displayed this tendency.
      These results suggest that stereotypes can be used as political weapons.

PMID- 11446232
TI  - The effects of reasons given for ineligibility on perceived gender discrimination
      and feelings of injustice.
AB  - We examine whether the reason given for a negative outcome influences the
      likelihood of making gender discrimination attributions. Men and women were given
      one of four reasons for their ineligibility to attend an event: an explicit
      gender reason, a reason based on an attribute correlated with gender, that same
      gender-related reason with explanatory information attached, or they were given
      no reason. Providing participants with a reason based on a gender-related
      attribute deflected them from making attributions to gender discrimination,
      indicating that discrimination attributions can easily be averted. Adding
      explanatory information to the gender-related reason decreased feelings of
      injustice, illegitimacy and anger while increasing acceptance of the outcome.

PMID- 11446233
TI  - Autobiographical memory and parasuicide in borderline personality disorder.
AB  - BACKGROUND: Several studies have found that parasuicidal patients are poor at
      recalling specific autobiographical memories when tested with the word-cueing
      paradigm and two studies have reported some evidence that over-general recall is
      a risk factor for repetition of parasuicide. The aim of the present study was to
      test whether this association could be replicated with a sample of patients
      suffering from borderline personality disorder (BPD). METHOD: Twenty-three
      patients with BPD completed a version of the Autobiographical Memory Test (AMT)
      and self-report measures of depression, anxiety and trait anger. In a structured
      interview, they also reported the number of times they had engaged in
      parasuicidal acts during the previous 4 months. RESULTS: The number of general
      memories produced on the AMT made a significant contribution to the prediction of
      the frequency of parasuicidal acts in a multiple regression analysis but the
      partial correlation in the final equation was negative. That is, those who showed
      greatest over-general recall reported fewest parasuicidal acts. Anxiety and
      depression, but not trait anger, also made significant independent contributions
      to the prediction of parasuicide. CONCLUSION: Over-general autobiographical
      recall may help to protect borderline individuals from parasuicidal acts by
      helping them to avoid distressing memories.

PMID- 11446234
TI  - Autobiographical memories become less vivid and emotional after eye movements.
AB  - OBJECTIVES: To test (1) whether eye movements during retrieval of emotional
      memories are followed by less vividness and less emotionality of future
      recollections, (2) whether this effect, if present, is stronger than the effects
      of a control activity (finger tapping), (3) whether the alleged effects of
      tapping and eye movements are stronger than a no-movement, control condition
      (mere imagery), (4) whether reductions in vividness and emotionality after eye
      movements (and finger tapping) are specific to negative memories or also occur in
      the case of positive memories. METHOD: Sixty healthy volunteers recalled either
      positive or negative memories and scored the vividness and emotionality of the
      recollections. Next, memories were recalled whilst the participant was performing
      rapid eye movements, finger tapping, or not performing a dual task. Then
      participants were asked to recall the event again and to rate its vividness and
      emotionality. RESULTS: Compared to finger tapping and the no-dual-task condition,
      recollections after eye movements made future recollections less vivid. After eye
      movements, but not after the other interventions, negative memories became less
      negative, and positive memories became less positive. CONCLUSION: The findings
      show that eye movements not only reduce vividness and emotionality of memories
      during the eye moving, but also affect future recollections, during which no eye
      movements are made. Some theoretical explanations are discussed. As to clinical
      implications, it is suggested that if there is a role for eye-movement-based
      treatments, it is very limited.

PMID- 11446235
TI  - Moderators of trainee therapists' competence in cognitive therapy.
AB  - OBJECTIVES: A revised version of the Cognitive Therapy Scale (CTS-R) was
      developed and used in an ecologically valid study designed to examine the
      acquisition of competence in cognitive therapy (CT). The relationship of
      therapist and patient variables to changes in competence was examined. Unlike
      most previous research, this study defines effectiveness of training in terms of
      therapist competence rather than patient outcome. DESIGN: A longitudinal design
      was employed within a naturalistic setting. Trainees' competence (the dependent
      variable) was sampled on three occasions during a training course. METHODS:
      Twenty screened out-patients, who had been routinely referred to the Newcastle
      Cognitive Therapy Centre, were assigned to 20 postgraduate trainees receiving
      training in CT. Expert raters assessed trainees' competence at three points over
      the first 12 sessions of treatment using the CTS-R. The relationship of therapist
      and patient variables to changes in competence was examined. The patient measures
      used were the Beck Depression Inventory (BDI) and the Suitability for Short-Term
      Cognitive Therapy (SSCT). RESULTS: Three therapist factors were found to be
      related to competence: time (trainee therapists improving over the training
      period), previous experience with CT (those with most experience were most
      competent), and gender of the therapist (males improving at a greater rate than
      females). Therapist competence was also related to patients' suitability.
      CONCLUSIONS: These findings suggest that previous CT experience is an advantage
      prior to attending an advanced training course, and also that careful patient
      selection helps trainees to demonstrate therapeutic competence.

PMID- 11446236
TI  - Recall bias, pain, depression and cost in back pain patients.
AB  - OBJECTIVES: To investigate the relationship between recall bias for pain stimuli
      in chronic low back pain patients and the cost of managing their back pain in
      primary care. DESIGN: A retrospective cross-sectional investigation. METHOD: A
      sample of 63 low back pain patients were interviewed in a primary care setting.
      Information was gathered on their pain intensity, disability ratings, depression,
      anxiety, and duration of pain. They were also presented with a surprise recall
      test for pain descriptors. The cost of each patient's treatment specifically for
      back pain in the previous 12 months was calculated. The relationship between the
      cost of back pain treatment and the scores from the interview were calculated
      first for total cost, and then for the breakdown of individual cost items.
      RESULTS: Results indicated that recall bias for pain stimuli were significantly
      related to total cost (R2 = 8%). A detailed analysis revealed that pain intensity
      was related to the number of appointments with the general practitioners;
      depression scores related to the number of appointments with the in-house
      osteopaths; and recall bias for pain stimuli related to referrals to external
      experts (out-patients). A minority of patients high on recall bias was found to
      account for a disproportionate amount of the cost. CONCLUSION: Although no causal
      path can be deduced from the findings, the study provides a novel approach to
      measuring psychological factors in back pain in reference to health care
      utilization. It is limited by its retrospective design, and should be followed by
      prospective studies to understand fully the relationship between cognitive bias
      and utilization of health services.

PMID- 11446237
TI  - Processing of threat-related affect is delayed in delusion-prone individuals.
AB  - OBJECTIVES: On the basis of previous reports of an attentional bias for threat
      related emotional material in deluded schizophrenics (e.g. Bentall & Kaney,
      1989), the present study examined the proposal that a similar bias would be
      demonstrated by delusion-prone individuals, reflected by longer response
      latencies for the task of processing threat-related facially displayed affects
      (e.g. anger, fear). DESIGN: A non-randomized matched group design was employed to
      examine the performance of delusion-prone individuals in comparison with a
      control group. METHODS: 50 psychiatrically healthy participants completed the
      Peters et al. Delusions Inventory (PDI) as an index of delusional ideation
      (Peters, Day, & Garety, 1996; Peters, Joseph, & Garety, 1999). Subjects were
      presented with a standard set of facial stimuli depicting happy, sad, neutral,
      fearful and angry emotion expressions (Mazurski & Bond, 1993). Reaction times for
      the task of identifying each type of affect were compared between groups of high
      and low scorers on the PDI. RESULTS: Highly delusion-prone individuals displayed
      a significant delay in processing angry facial expressions in comparison with low
      scorers on the PDI. CONCLUSIONS: The increased response latency for processing
      angry expressions was interpreted as evidence of attentional bias for material
      posing a threat to the self, supporting previous cognitive data in relation to
      deluded patients. Threatening facial expressions may be regarded with increased
      significance by delusion-prone individuals, and it is possible that this bias is
      involved in the formation of delusional beliefs.

PMID- 11446238
TI  - Perception of negative emotions in close relatives by patients with
      schizophrenia.
AB  - OBJECTIVES: The perception of negative emotions in close relatives may play an
      important role in explaining how external stressors can affect vulnerable
      individuals with schizophrenia. However, there is considerable debate about the
      ability of people with schizophrenia to perceive emotions in others. The present
      study aimed to examine the reliability of patients' perception of relatives'
      criticism. Secondly, it aimed to investigate whether patients' judgement about
      relatives' criticism agreed with an independent assessment of relatives'
      criticism towards patients. METHOD: Forty-three patients with a DSM-III-R
      diagnosis of schizophrenia and their relatives were assessed soon after patients'
      admission to a psychiatric hospital and again 9 months after their discharge from
      hospital. Test-retest reliability of patients' answers to a question about
      patients' perception of relatives' criticism towards them was carried out. The
      association between patients' perception of relatives' criticism and the
      expressed emotion (EE) measure of relatives' criticism was examined at inclusion
      and follow-up. Patients' symptomatology was examined at both assessments.
      RESULTS: Reliability of the measurement of patients' perception of relatives'
      criticism was moderate to good. Patients' judgement of relatives' criticism
      towards them was associated with the number of critical comments and presence of
      hostility at inclusion. At follow-up, this association became weaker. CONCLUSION:
      The ability to judge and describe reliably negative emotions in close
      relationships may help to explain how perception of the external environment may
      act as a stressor in people who are vulnerable to schizophrenia.

PMID- 11446239
TI  - Obesity-related coping and distress and relationship to treatment preference.
AB  - OBJECTIVES: The primary purpose was to define obesity-related strategies for
      coping with psychological problems connected with obesity. We also wanted to
      identify obesity-related distress and explore the effect of coping on distress.
      Thirdly, we wanted to investigate differences in coping and distress related to
      choice of surgery or conventional treatment. DESIGN: Cross-sectional data from
      patients in the Swedish Obese Subjects (SOS) intervention study. METHODS: An
      obesity-related questionnaire concerning coping and distress was created and
      evaluated in 2510 patients from the SOS study, using multitrait, exploratory and
      confirmatory factor analysis procedures. RESULTS: Three coping factors were
      defined. Social Trust and Fighting Spirit were problem-focused, whereas Wishful
      Thinking was emotion-focused. Surgical candidates displayed lower levels of
      problem-focused and higher levels of emotion-focused coping. We also identified
      two distress factors: Intrusion and Helplessness. Wishful Thinking was positively
      related to distress, and Social Trust and Fighting Spirit were inversely related,
      thus explaining the higher levels of distress reported by the surgical
      candidates. CONCLUSIONS: In our sample, emotion-focused coping proved maladaptive
      and was associated with increased distress. Problem-focused coping, however, was
      adaptive and associated with reduced distress. These findings partly explain
      psychological morbidity and should be taken into consideration in the treatment
      of obese people.

PMID- 11446240
TI  - Compliance and outcome in treatment-resistant anorexia and bulimia: a
      retrospective study.
AB  - OBJECTIVES: To investigate the extent to which compliance with treatment is
      related to outcome, and factors associated with compliance in a group of
      treatment-resistant eating-disordered in-patients. DESIGN: A retrospective case
      study design was employed where clinic staff made expert ratings of eating
      behaviours, attitudes and outcome of former in-patients. METHOD: Ten health-care
      staff at a specialist eating disorders clinic rated overall success of treatment
      outcome at discharge, as well as compliance, severity of disordered eating
      behaviours and body-image disturbance at both admission and discharge for 46
      anorexic and 14 bulimic patients. RESULTS: For all participants, high compliance
      at admission was associated with lower levels of body image disturbance, less
      disordered eating behaviours and higher ratings of overall treatment success at
      discharge. Compliance at admission predicted the body mass index (BMI) at
      discharge for anorexic participants and predicted higher ratings of overall
      treatment success at discharge for all participants. In all participants,
      compliance at admission was related to the extent of eating-disordered behaviours
      at admission. CONCLUSIONS: Results suggest the importance of compliance in
      facilitating recovery and treatment success among treatment-resistant eating
      disordered in-patients. The promotion of strategies to improve compliance in this
      population should be considered. A role for motivational interviewing is
      discussed.

PMID- 11446241
TI  - Coping and psychological distress in children involved in road traffic accidents.
AB  - OBJECTIVE: The purpose of this study is to detail the natural coping strategies
      used by children involved in everyday road traffic accidents (RTAs). The
      relationship between coping strategies, post-traumatic stress disorder (PTSD),
      gender and age was investigated. DESIGN: Children aged 7-18 who attended an
      accident and emergency department following involvement in a RTA were assessed, 6
      weeks after their accident (N = 97). A subgroup of 36 children were re-assessed
      approximately 8 months after the trauma. METHODS: The presence of PTSD was
      determined via a semi-structured interview incorporating the Clinician
      Administered Post-traumatic Scale for Children (CAPS-C). Self-completed
      psychometric assessments were undertaken to assess the presence of clinically
      significant levels of depression (Birleson Depression Inventory), anxiety
      (Revised Manifest Anxiety Scale) and coping style (Kidcope). RESULTS: Children
      involved in RTAs used between 5 and 7 different coping strategies. Younger
      children and those with PTSD used more strategies than older children and those
      not suffering from PTSD. Children with PTSD were more likely to use the
      strategies of distraction, social withdrawal, emotional regulation and blaming
      others. CONCLUSION: The limitations of Kidcope are discussed and the need to
      develop more complex ways of assessing childhood coping within a developmental
      framework highlighted.

PMID- 11446242
TI  - The ability of naive participants to report symptoms of post-traumatic stress
      disorder.
AB  - OBJECTIVE: Research suggests that naive participants can simulate PTSD (post
      traumatic stress disorder) using a symptom checklist. Is successful faking of DSM
      IV criteria B-D on PTSD checklists due to prior knowledge of PTSD, the leading
      nature of symptom checklists, or a combination? DESIGN: Between-groups design.
      METHOD: Naive participants self-generated PTSD symptoms from a vignette. They
      were then randomly assigned to groups given a standard symptom checklist or a
      checklist containing bogus items not normally associated with PTSD. RESULTS: Less
      than 1% self-generated symptoms that met DSM-IV criteria B-D for PTSD. It was
      found that 94% of participants satisfied these criteria using the standard
      checklist and 90% on the modified checklist. Participants incorrectly identified
      38% of bogus symptoms as symptoms of PTSD. CONCLUSIONS: Despite poor prior
      knowledge of PTSD, 94% of participants fulfilled diagnostic criteria using a
      standard checklist. This is probably due to symptom 'guessing'.

PMID- 11446243
TI  - Effects of retrieving childhood events on metamemory judgments depend on the
      questions you ask.
AB  - OBJECTIVE: The more people retrieve childhood memories, the less favourably they
      evaluate their own memory. It has been argued that this might play a role in self
      reports of amnesia. However, a limitation of previous studies addressing this
      phenomenon is that participants' judgments about their memory were based on a
      single item. DESIGN: Students were randomly assigned to either of two conditions.
      In one condition, they were asked to retrieve nine negative childhood events,
      whereas in the other condition, participants were required to recall three
      events. METHOD: After recall, students completed measures on memory accessibility
      and 'repression'. RESULTS: Students who retrieved nine events rated their
      memories as less accessible, but also reported less repression than did students
      who retrieved three events. CONCLUSION: The direction of retrieval effects on
      metamemory judgments depends on the way in which questions are framed.

PMID- 11446244
TI  - Utility of a demographic equation in detecting impaired NART performance after
      TBI.
AB  - OBJECTIVES: This study applies a demographic regression equation devised by
      Crawford, Allan, Cochrane, and Parker (1990) to determine its utility in New
      Zealand, and to determine the proportion of persons with traumatic brain injury
      (TBI) with impaired performance on the National Adult Reading Test (NART).
      METHOD: The NART was administered to 80 community participants, 65 people with
      traumatic brain injury (TBI), and 27 orthopaedic controls. The Crawford et al.
      (1990) equation was applied to all three samples. RESULTS: The Crawford et al.
      (1990) equation was applicable in the New Zealand community sample. It was found
      that 30% of the TBI sample had impaired performance on the NART. Using corrected
      NART scores, a significantly larger proportion of the TBI sample was detected as
      intellectually impaired than in the control sample. CONCLUSION: Nearly one-third
      of the TBI sample evidenced impaired performance on the NART. Consequently,
      clinicians that use the NART in assessing people with TBI should use the
      demographic equation to check the accuracy of NART performances, and correct the
      NART scores if this is indicated.

PMID- 11446245
TI  - Defense Department takes on depression guidelines.
AB  - The process developed by the U.S. Department of Defense in creating evidence
      based guidelines for the treatment of depression serves as an instructive guide
      both for payers and health care delivery systems.

PMID- 11446246
TI  - Early, aggressive treatment can boost arthritis outcomes.
AB  - Those with osteoarthritis or rheumatoid arthritis can consider several new care
      strategies. They come with the risk of rare, though serious, side effects.

PMID- 11446248
TI  - Heart center boosts outcomes with new profiling tool.
AB  - A South Carolina cardiac rehab center co-developed a suite of reports that helped
      its staff and referring cardiologists to obtain real-time information on the
      health status of one or a group of patients. The strategy replaces the previous
      approach of relying on retrospective analysis.

PMID- 11446249
TI  - Follow new pediatric guidelines or risk inappropriate care, liability.
AB  - If you don't comply with new guidelines for pediatric emergency care jointly
      developed by the American College of Emergency Physicians and American Academy of
      Pediatrics, you risk adverse outcomes and lawsuits. When transferring a
      critically ill or injured child, use transport services with specific pediatric
      training. Have a physician and nursing coordinator ensure compliance with the
      guidelines. Ensure that staff are trained in pediatric resuscitation, and provide
      age-specific competencies for neonates, infants, children, and adolescents.

PMID- 11446250
TI  - Educate patients, cut return asthma visits.
AB  - An effective asthma education program can reduce return visits to the ED and
      adverse outcomes. The program should be tracked to ensure that every asthma
      patient receives education. ED nurses should work collaboratively with
      respiratory therapists. Patients should be called shortly after their ED visit to
      ensure they understand their discharge instructions and have made follow-up
      appointments.

PMID- 11446251
TI  - Don't miss payments during observation.
AB  - Under ambulatory payment classifications (APCs), there is no separate
      reimbursement for observation itself, but you can get paid for procedures
      performed during observation. Educate nurses and physicians about which
      procedures can be billed separately, including injections and i.v. medication
      administration. Use coders who are specially trained for ED visits. Review the ED
      chargemaster to make sure the list of procedures is complete.

PMID- 11446252
TI  - EMTALA Q&A. Blood alcohol screenings.

PMID- 11446257
TI  - Neurognostics: question 12: glischroidie.

PMID- 11446258
TI  - The subfornical and subcommissural organs: never-ending rediscoveries.

PMID- 11446259
TI  - The decade of the brain--a decade of scholarship. A bibliography of the History
      of the Neurosciences, 1990-2000.

PMID- 11446260
TI  - Luis Simarro Lacabra [1851-1921]: from Golgi to Cajal through Simarro, via
      Ranvier?
AB  - Knowledge of cerebral structure and function in its modern form can be traced to
      the neurone doctrine based largely on the work of Santiago Ramon y Cajal [1852
      1934] and his lifelong exploitation of the Golgi method. Cajal openly
      acknowledged his debt to the neuropsychiatrist Luis Simarro Lacabra [1851-1921]
      who introduced him to the method in 1887, and recalled that the sight of the
      silver-impregnated nerve cells was the turning point which led him to abandon
      general anatomy and concentrate on neurohistology. Simarro, who dissipated his
      free time in trying to improve not only the scientific but also the political
      world around him, was able to produce exciting Golgi preparations of the cerebral
      cortex after he returned from voluntary exile in Paris from 1880 to 1885.
      Certainly it was there that he learned the methods of experimental histology from
      Louis-Antoine Ranvier [1835-1922] whose laboratory exercises, in the guise of
      lectures, he attended assiduously.

PMID- 11446261
TI  - Neuro-anniversary 2001.

PMID- 11446262
TI  - About medicine and the arts. Charcot and French literature at the fin-de-siecle.
AB  - The relationship between medicine and the arts, literature in particular, has
      many aspects. One of the most obvious relations is the use of literature as a
      source for historical studies. Jean-Martin Charcot and his school often appear in
      French literature at the end of the 19th century. Several aspects will be
      highlighted in this study, including (1) the ideas about degenerative diseases in
      the work of Emile Zola, the main author of the naturalistic movement; (2)
      decadence and spiritism in two "transitional" novels by Joris Karl Huysmans, who,
      once supporter of the naturalistic movement, changed his ideas following
      observations of disease and cure that could not be explained in a scientific way.
      Charcot's work on hysteria and hypnosis, as well as Brown-Sequard's rejuvenation
      experiments with testicular extracts played an important role with this respect;
      (3) Charcot's relationship with the Daudets, in particular his treatment of
      Alphonse's tabes dorsalis and the ambivalent attitude of his son Leon Daudet
      towards Charcot; (4) the influence of the lectures at the Salpetriere on the work
      of Guy de Maupassant, who attended the lessons in the mid-1880s. The reading of
      novels and biographies of these authors provides a part of the social context and
      the cultural atmosphere in Paris at the "fin-de-siecle" when Charcot and his
      school played an important role in medicine. Moreover, it shows the influence of
      medicine and science on society as recorded by writers.

PMID- 11446263
TI  - Edward Albert Schafer (Sharpey-Schafer) and his contributions to neuroscience:
      commemorating of the 150th anniversary of his birth.
AB  - The year 2000 marks the 150th anniversary of the birth of Edward Albert Schafer
      (Sir Edward Albert Sharpey-Schafer). Affiliated first with University College,
      London, and then with Edinburgh University, Schafer made monumental contributions
      to the fields of histology, physiology, endocrinology, and practical medicine.
      This paper traces his professional life and emphasizes his seminal contributions
      to the neurosciences, which include his findings in support of neuron doctrine,
      his research on cortical localization in monkeys, his discovery of adrenaline and
      its place in the history of neural transmission, and his studies on recovery
      after nerve damage. Author of many histology and physiology books, founder of the
      "Quarterly Journal of Experimental Physiology," and mentor to many students who
      achieved great fame themselves, Schafer was an active teacher and researcher, a
      man who remained committed to his vision of medicine based on laboratory science
      until he died in 1935.

PMID- 11446264
TI  - Pioneers of affective neuroscience and early concepts of the emotional brain.
AB  - Views on the representation of emotion in the brain, as formulated about a
      century ago, are described, with a focus on the Vienna physiologist and
      psychologist Sigmund Exner, the psychoanalyst Sigmund Freud, and the French
      physician Israel Waynbaum. All three can be characterized as forerunners in the
      field of "affective neuroscience". By the turn of the century, they had developed
      a neural network theory of emotion which included a stage of pre-cortical
      processing. In spite of their otherwise very diverse theoretical backgrounds,
      their concepts of parallel processing routes were highly similar. It is
      interesting to note that their ideas were on line with present-day views on the
      neural substrates and physiological characteristics of emotional processing,
      although none of the three scientists could rely on the refined anatomical
      knowledge available nowadays.

PMID- 11446265
TI  - The originality of Descartes' theory about the pineal gland.
AB  - Rene Descartes thought that the pineal gland is the part of the body with which
      the soul is most immediately associated. Several prominent historians (such as
      Soury, Thorndike and Sherrington) have claimed that this idea was not very
      original. We re-examine the evidence and conclude that their assessment was
      wrong. We pay special attention to the thesis about the pineal gland which Jean
      Cousin defended in January, 1641.

PMID- 11446266
TI  - Kurt Goldstein--a philosophical scientist.
AB  - Kurt Goldstein was one of the major proponents of the holistic movement which was
      opposed to the classical connectionist Wernicke-Lichtheim-Model in aphasiology at
      the beginning of the 20th century. Influenced by Kant, Husserl and Cassirer, his
      work goes beyond purely empirical research and approaches traditionally
      philosophical questions: How can we proceed from empirical data to a theory
      adequately reflecting reality? How can we understand man as mind and body? What
      is the relation between language and cognition? Goldstein's concepts of
      biological knowledge, self-actualization and abstract attitude seek to address
      these questions. His work thus becomes attractive for philosophers. It was taken
      up and interpreted by Cassirer, Merleau-Ponty and Gurwitsch.

PMID- 11446267
TI  - Dr. Gottlieb Burckhardt--the pioneer of psychosurgery.
AB  - The first attempt at psychosurgery--intentional damage to the intact brain for
      the relief of mental illness--was undertaken in 1888 by the Swiss psychiatrist
      Gottlieb Burckhardt. Six chronic schizophrenic patients underwent localized
      cerebral cortical excisions. Most patients showed improvement and became easier
      to manage, although one died from the procedure and several had aphasia or
      seizures. Burckhardt, a learned neuropsychiatrist, presented his results in 1890
      and in 1891 published his scientific rationale and detailed clinical outcome in a
      scholarly paper. Nevertheless his approach had shocked the medical community as
      reckless and irresponsible. Burckhardt was ridiculed, his academic endeavors
      ceased and his surgical endeavor largely ignored. Nevertheless he continued
      practice as a fine psychiatrist and mental hospital director. Burckhardt's career
      and interesting ideas on higher cerebral functions are reviewed and placed in
      perspective regarding the development of "modern" psychosurgery almost one-half
      century later.

PMID- 11446268
TI  - Lesions as therapy: rigidity and Parkinson's disease.
AB  - Since James Parkinson (1817) first characterized the shaking palsy as a unique
      condition, significant confusion has remained concerning the causes and
      treatments of Parkinson's disease (PD). Through the 19th century, a wide variety
      of approaches were attempted in an effort to reduce its cardinal signs--rigidity,
      tremor, and bradykinesia--but to little effect. Today, approaching 200 years
      after Parkinson's seminal work, this disorder is commonly treated by surgical
      means, inducing a lesion in one specific portion of a small nucleus in the
      central nervous system (Desaloms et al., 1998, Lang et al., 1999). The notion of
      providing a lesion to the nervous system as a therapy for PD, however, began in
      earnest at the beginning of the 20th century. The first attempt to alleviate the
      symptoms of PD through surgical means involved a section of the dorsal roots of
      the spinal cord supplying the affected limb (also known as dorsal rhizotomy).
      Although ultimately resulting in disastrous effects, these early surgical
      attempts proceeded from a firm body of clinical and experimental research on both
      the central and peripheral nervous systems. After briefly reviewing the use and
      failure of dorsal rhizotomy as a treatment for parkinsonian rigidity, this paper
      will examine the manner in which clinicians and scientists justified the
      procedure.

PMID- 11446269
TI  - Valsartan and the kidney: review of preclinical and clinical data.
AB  - In both diabetic and nondiabetic renal disease, reducing blood pressure with
      antihypertensive therapy has beneficial effects on renal function. The key role
      of the renin-angiotensin system in blood pressure and volume homeostasis has long
      been established, but its importance for the overall normal functioning of the
      kidney itself is also increasingly being recognized. Angiotensin-converting
      enzyme (ACE) inhibitors, widely and successfully used in the treatment of
      hypertension, may also provide renal protection independent of blood pressure
      reduction; however, their relatively nonspecific mode of action in blocking an
      early metabolic step entails major clinical disadvantages, such as accumulation
      of bradykinin and substance P, that may cause the characteristic ACE-inhibitor
      side effects of persistent dry cough and, more rarely, angioneurotic edema.
      Angiotensin II antagonists or receptor blockers, a new class of antihypertensive
      agent, selectively antagonize the AT1 receptor subtype and, because of greater
      specificity, do not give rise to the side effects associated with ACE inhibitors.
      More important, these new drugs may have mechanistic advantages over other
      antihypertensives, including ACE inhibitors.

PMID- 11446270
TI  - Intensive postremission chemotherapy in Taiwanese adults with acute myelogenous
      leukemia.
AB  - Intensive postremission chemotherapy has produced disease-free survival
      comparable to that of bone marrow transplantation in patients with acute
      myelogenous leukemia (AML), but its efficacy was unknown in Taiwan. We assessed
      the efficacy of intensive postremission chemotherapy, consisting of high-dose
      arabinoside-C (HiDAC) with or without transplantation of peripheral blood stem
      cells, in 33 AML patients from a single institute in Taiwan. Toxic reactions,
      treatment outcome, prognostic factors, and the size of the peripheral blood stem
      cell harvest after HiDAC were analyzed. After a median follow-up of 21 months, 18
      patients remained in continuous complete remission. The actuarial leukemia-free
      survival at 4 years was 51%. Relapse occurred in 12 patients, at a median of 12
      months after initial diagnosis. All 6 patients with acute promyelocytic leukemia
      remained disease free after HiDAC therapy. Age, sex, and number of remission
      induction or intensive consolidation chemotherapy courses had no effect on the
      risk of relapse. Intensive postremission chemotherapy can effectively prolong the
      duration of remission in young (< 60 years of age) adults with AML.

PMID- 11446271
TI  - Anti-inflammatory activity of clarithromycin in adults with chronically inflamed
      sinus mucosa.
AB  - In a phase IV, open-label study, 25 patients with clinically stable chronic
      sinusitis and persistent maxillary sinus inflammation were treated for 14 days
      with clarithromycin 500 mg twice daily. Biopsy specimens of the maxillary sinus
      mucosa were obtained pretreatment and evaluated for macrophages (CD68),
      eosinophils (MBP), elastase, interleukin-6 (IL-6), IL-8, tumor necrosis factor
      alpha (TNF-alpha), and activity of eosinophils (EG2), as well as edema score.
      Clinical signs and symptoms were assessed pretreatment, at the end of treatment,
      and 1 and 2 weeks later. Statistically significant reductions (P < or = .05) from
      pretreatment were observed for all markers of sinus mucosal inflammation,
      including CD68, EG2, elastase, IL-6, IL-8, TNF-alpha, and edema score, with a
      trend to decreased total eosinophil count. Improvement was observed for all
      clinical signs and symptoms of chronic sinusitis--sinus pain, sinus headache,
      nasal congestion, nasal discharge, and mucopurulent discharge--up to 14 days
      after the end of treatment. Cultures to evaluate persistent infection with
      Chlamydia pneumoniae showed negative results. Significant reductions in various
      markers of sinus mucosal inflammation support the role of clarithromycin in
      modulating immunologic responses. Improvement of clinical signs and symptoms in
      patients with chronic inflammatory sinusitis not meeting criteria for known or
      presumed bacterial infection was also noted up to 2 weeks after completion of a
      14-day course of clarithromycin.

PMID- 11446272
TI  - The death of electroconvulsive therapy.
AB  - In Italy, where it began more than 62 years ago, ECT has almost been abolished.
      In some countries, however, ECT is still used inappropriately, particularly in
      elderly patients. There is no medical, moral, or legal justification for ECT, and
      the new requirements of modern psychiatric practice can all be achieved without
      it. Like prefrontal lobotomy and all previous shock treatments, ECT is nonviable.
      The death of ECT will help promote mental health and put the treatment where it
      belongs--in the archaeology of science.

PMID- 11446273
TI  - The effects of Silicol Skin on moderate to severe acne: UK field survey.
AB  - This field survey assessed the effect of the natural trace element silicon, the
      active ingredient in Silicol Skin, on moderate to severe acne. Members of the
      Acne Support Group used Silicol Skin for 6 weeks, completing identical
      questionnaires on the type and severity of acne before and after treatment. A
      statistically significant 86% overall improvement was reported, with most
      participants citing the chin as showing the greatest change. Total disappearance
      of acne was noted in some locations. Results did not differ significantly between
      the group that used Silicol Skin alone and the group that added it to their
      prescribed oral medication. Silicol Skin can help improve moderate to severe
      acne.

PMID- 11446274
TI  - Community coalition building--contemporary practice and research: introduction.
AB  - Over the last 20 years, coalition building has become a prominent intervention
      employed in communities across America. Coalitions provide community
      psychologists and those in related fields with a chance to work with whole
      communities and to better understand how to create community change. As we
      reflect on the past two decades of community coalition building, there are many
      questions to be answered about this phenomenon. Why has there been such an
      upsurge in community coalition building activity? What is the impact of this
      activity? What have we as students of community learned? What are the questions
      that we need to be asking to improve the effectiveness of coalition building
      efforts and their evaluation? This set of articles will review the state of the
      art of community coalition building in both practice and research. The structure
      of the articles reflects a collaborative process, with multiple contributors from
      different disciplines, using a variety of formats. Because this is an evolving
      phenomenon where the questions asked are as important as the lessons learned,
      many of the major sections include dialogues with community experts from across
      the country and from multiple fields, including community psychology, public
      health, political science, public administration, and grassroots organizing.

PMID- 11446275
TI  - A practitioner's guide to successful coalitions.
AB  - The highly complex practice of building successful community coalitions is
      explored. Key dimensions related to coalition success are identified and best
      practices are delineated. Nine dimensions are explored that are critical to
      coalition success: coalition readiness, intentionality, structure and
      organizational capacity, taking action, membership, leadership, dollars and
      resources, relationships, and technical assistance. Two coalition case studies
      follow the discussion of dimensions and illustrate the journey traveled to create
      successful community coalitions.

PMID- 11446276
TI  - Case story #1: Building the grassroots coalition.

PMID- 11446277
TI  - Case story #2: Growing a healthy community: a practical guide.

PMID- 11446278
TI  - Studying the outcomes of community-based coalitions.
AB  - Community-based coalitions are popular structures for creating community
      benefits. But desired effects have been reported only for single cases, the
      overall documented evidence to date for positive coalition outcomes being weak.
      Methodological obstacles may account for much of the missing evidence, and
      research possibilities for addressing these obstacles are suggested. Alternative
      interpretations include the positions that coalitions in general are not
      effective intervention mechanisms, that traditional scientific methodology is
      poorly suited for capturing fine-grained coalition outcomes, and that coalitions
      and similar collaborative organizations are too complex to be adequately
      evaluated by the methodology that is now available.

PMID- 11446279
TI  - Building collaborative capacity in community coalitions: a review and integrative
      framework.
AB  - This article presents the results of a qualitative analysis of 80 articles,
      chapters, and practitoners' guides focused on collaboration and coalition
      functioning. The purpose of this review was to develop an integrative framework
      that captures the core competencies and processes needed within collaborative
      bodies to facilitate their success. The resulting framework for building
      collaborative capacity is presented. Four critical levels of collaborative
      capacity--member capacity, relational capacity, organizational capacity, and
      programmatic capacity--are described and strategies for building each type are
      provided. The implications of this model for practitioners and scholars are
      discussed.

PMID- 11446280
TI  - The future of community coalition building.
AB  - The future holds great promise for community coalitions as powerful interventions
      for community change. Community change is envisioned as: working with whole
      communities; increasing grassroots and civic engagement; promoting diversity,
      collaboration and, advocacy; increasing roles for professional technical
      assistance and evaluation; future changes in the role of government; and the
      building of healthy communities. Examples of these dimensions follow, as
      contributed by activists from a wide range of fields.

PMID- 11446281
TI  - Grassroots involvement.

PMID- 11446282
TI  - On coalitions and the transformation of power relations: collaborative betterment
      and collaborative empowerment.

PMID- 11446283
TI  - Coalition-building: the promise of government.

PMID- 11446284
TI  - Using Internet-based resources to build community capacity: the Community Tool
      Box [http://ctb.ukans.edu/].

PMID- 11446285
TI  - America's communities movement: investing in the civic landscape.

PMID- 11446286
TI  - The paradoxes and promise of community coalitions.
AB  - Community coalitions, as they are currently applied, are unique organizations
      whose ability to promote community change is different from other types of
      community organizations. This article explores those differences and elaborates
      how community coalitions can use those differences to transform conflict into
      greater capacity, equity, and justice. Concerns are also raised in this article
      about how community coalitions can intentionally and unintentionally protect the
      status quo and contain the empowerment of grassroots leadership and those of
      marginalized groups. There is a need for more theory, research, and discourse on
      how community coalitions can transform conflict into social change and how they
      can increase the power of grassroots and other citizen-lead organizations.

PMID- 11446287
TI  - Understanding dignity in the lives of homeless persons.
AB  - The current investigation is a planned, systematic study of dignity as critical
      to understanding the experience of homelessness and improving services and
      programs for the homeless. Specifically, we conducted a thematic content analysis
      of interviews with 24 homeless men and women to identify their perception of
      specific environmental events that validate and invalidate dignity. In addition,
      we explored the impact that these events have on homeless persons. Eight types of
      events were identified that sustain dignity such as being cared for by staff and
      having resources available to meet basic needs. Eight types of events were found
      that undermine dignity, such as being yelled at or insulted by staff persons and
      having staff use rules in an excessive and arbitrary way. Two outcomes followed
      the sustenance of dignity including increased self-worth and motivation to exit
      homelessness. Three outcomes followed the undermining of dignity including anger,
      depression, and feelings of worthlessness. The results suggest that dignity is an
      important variable to consider in understanding the experience of homelessness.
      Policies and programs that support validating the dignity of homeless persons are
      encouraged.

PMID- 11446288
TI  - Life stressors, social support, and depressive symptoms among first-time welfare
      recipients.
AB  - This paper examines the associations among stressful life events, social support,
      and depressive symptoms in a sample of 580 first-time welfare recipients. Self
      reported number of depressive symptoms was greater than in corresponding
      community samples. Stressors and social supports made independent main effect
      contributions to depressive symptoms in a multiple regression analysis. Women
      with transportation barriers to employment, those experiencing greater numbers of
      stressful life events, and those who were less satisfied with their housing
      situation reported greater numbers of depressive symptoms. In contrast, women who
      were more satisfied with their social support and those with higher attendance at
      religious services reported fewer depressive symptoms. Implications for welfare
      reform policy and programs are discussed.

PMID- 11446289
TI  - Mapping residents' perceptions of neighborhood boundaries: a methodological note.
AB  - Neighborhood influences on children and youth are the subjects of increasing
      numbers of studies, but there is concern that these investigations may be biased,
      because they typically rely on census-based units as proxies for neighborhoods.
      This pilot study tested several methods of defining neighborhood units based on
      maps drawn by residents, and compared the results with census definitions of
      neighborhoods. When residents' maps were used to create neighborhood boundary
      definitions, the resulting units covered different space and produced different
      social indicator values than did census-defined units. Residents' agreement about
      their neighborhoods' boundaries differed among the neighborhoods studied. This
      pilot study suggests that discrepancies between researcher and resident-defined
      neighborhoods are a possible source of bias in studies of neighborhood effects.

PMID- 11446290
TI  - Kairomonal response by four Monochamus species (Coleoptera: Cerambycidae) to bark
      beetle pheromones.
AB  - We investigated the hypothesis that wood-boring beetles in the genus Monochamus
      (Cerambycidae) utilize pheromones of sympatric bark beetles as host-finding
      kairomones. All nine bark beetle pheromones tested electrophysiologically were
      antenally active for both sexes of M. scutellatus, M. clamator, and M. obtusus
      from British Columbia. When field-tested with multiple-funnel traps (British
      Columbia) or cross-vane traps (Ontario), a blend composed of frontalin,
      ipsdienol, ipsenol, and MCH, in combination with a blend of host volatiles
      attracted significant numbers of M. clamator, M. obtusus, M. notatus, and M.
      scutellatus to baited traps. Traps baited with host volatiles in combination with
      a second blend composed of endo-brevicomin, exo-brevicomin, cis-verbenol, trans
      verbenol, and verbenone caught no more beetles than unbaited traps or traps
      baited with the host blend alone. In British Columbia, traps baited with the
      first blend alone or both blends together captured more M. scutellatus and M.
      clamator than unbaited traps, demonstrating a response to bark beetle pheromones
      in the absence of host volatiles. These results suggest that Monochamus spp. are
      minimizing foraging costs by using the pheromones of sympatric bark beetles as
      kairomones.

PMID- 11446291
TI  - Attraction of a leaf beetle (Oreina cacaliae) to damaged host plants.
AB  - Early in spring, just after the snow melts, the leaf beetle Oreina cacaliae feeds
      on flowers of Petasites paradoxus. Later in spring they switch to their principle
      host plant Adenostyles alliariae. The attractiveness of short- and long-term
      damaged host plants was studied in a wind tunnel. The spring host P. paradoxus
      was more attractive to the beetles after it had been damaged overnight by
      conspecifics or artificially, but not when the plants were damaged half an hour
      before the wind-tunnel experiments. Contrary to P. paradoxus, the principle host
      plant, A. alliariae was more attractive shortly after an attack by conspecifics
      (half an hour before the experiment) compared to a undamaged plant, but lost its
      increased attractiveness when damaged overnight. The enhanced attraction of
      damaged plants was longer lasting in the spring host P. paradoxus than in the
      main host A. alliariae. Volatiles emitted by host plants were collected and gas
      chromatographic analyses of the odors collected showed qualitative and
      quantitative differences between damaged and undamaged plants. Among the
      volatiles recorded, green leaf volatiles and mono- and sesquiterpenes dominated.
      In overnight damaged P. paradoxus plants with an enhanced attractiveness,
      limonene was emitted in higher amounts. In freshly damaged A. alliariae leaves,
      more alpha-humulene and germacrene D were emitted compared to (E,E)-alpha
      farnesene, whereas in the less attractive A. alliariae plants, more (E,E)-alpha
      farnesene was emitted compared to alpha-humulene and germacrene D. In the field,
      the long lasting attraction of flowering P. paradoxus early in the season may
      facilitate mating in O. cacaliae after a successful overwintering.

PMID- 11446292
TI  - Host location and host discrimination behavior of Telenomus isis, an egg
      parasitoid of the African cereal stem borer Sesamia calamistis.
AB  - In the Republic of Benin, the scelionid egg parasitoid Telenomus isis (Polaszek)
      is one of the most important control factors of the noctuid maize stem borer
      Sesamia calamistis. In the present study, the role of various sources of contact
      kairomones (male or virgin or mated female moths) and of the moth's oviposition
      substrate (leaf sheath versus filter paper: host plant species) in host location
      and oviposition behavior of T. isis was investigated in Munger cells, open
      arenas, and/or Petri dish assays. Furthermore, its ability to distinguish between
      unparasitized eggs and eggs parasitized by a conspecific female or by the
      trichogrammatid Lathromeris ovicida was studied. In the Munger cell experiment,
      T. isis spent more time in moths' odor fields than in the control. There was no
      difference between virgin and mated females. In the open arena assay, traces left
      by both the male and female moths acted as contact cues, which elicited an
      arrestment response in the parasitoid. The residence and patch retention time in
      the arena with virgin or mated females of S. calamistis was about 4.8 times as
      long as that with males. The presence of maize leaf sheaths stimulated the
      oviposition behavior of T. isis when compared to eggs offered on filter paper.
      During the first 6 hr, more eggs were parasitized on maize leaves, although there
      was no difference in the final number of offspring between the two substrates. In
      addition, if eggs of S. calamistis were offered together with different host
      plant species or alone, maize and sorghum were both more attractive than millet
      or the egg alone and equally attractive between themselves, indicating that the
      plant tissue influences host finding of T. isis. Both T. isis and L. ovicida
      recognized markings of conspecific females, and intraspecific superparasitism was
      therefore low. Interspecific superparasitism was more than three times higher for
      L. ovicida than for T. isis, indicating that only T. isis was able to recognize
      the marking of the other species and tried to avoid superparasitism. Emergence of
      parasitoids from multiparasitized eggs generally was in favor of L. ovicida
      regardless of species order.

PMID- 11446293
TI  - Exogenous methyl jasmonate induces volatile emissions in cotton plants.
AB  - We investigated the effect of exogenous methyl jasmonate (MeJA) on the emission
      of herbivore-induced volatiles; these volatile chemicals can signal natural
      enemies of the herbivore to the damaged plant. Exogenous treatment of cotton cv.
      Deltapine 5415 plants with MeJA induced the emission of the same volatile
      compounds as observed for herbivore-damaged plants. Cotton plants treated with
      MeJA emitted elevated levels of the terpenes (E)-beta-ocimene, linalool, (3E)-4,8
      dimethyl-1,3,7-nonatriene, (E,E)-alpha-farnesene, (E)-beta-farnesene, and (E,E)
      4,8,12-trimethyl-1,3,7,11-tridecatetraene compared to untreated controls. Other
      induced components included (Z)-3-hexenyl acetate, methyl salicylate, and indole.
      Methyl jasmonate treatment did not cause the release of any of the stored
      terpenes such as alpha-pinene, beta-pinene, alpha-humulene, and (E)-beta
      caryophyllene. In contrast, these compounds were emitted in relatively large
      amounts from cotton due to physical disruption of glands by the herbivores. The
      timing of volatile release from plants treated with MeJA or herbivores followed a
      diurnal pattern, with maximal volatile release during the middle of the
      photoperiod. Similar to herbivore-treated plants, MeJA treatment led to the
      systemic induction of (Z)-3-hexenyl acetate, (E)-beta-ocimene, linalool, (3E)-4,8
      dimethyl-1,3,7-nonatriene, (E,E)-alpha-farnesene, (E)-beta-farnesene, and (E,E)
      4,8,12-trimethyl-1,3,7,11-tridecatetraene. Our results indicate that treatment of
      cotton with MeJA can directly and systemically induce the emission of volatiles
      that may serve as odor cues in the host-search behavior of natural enemies.

PMID- 11446294
TI  - Response of some scolytids and their predators to ethanol and 4-allylanisole in
      pine forests of central Oregon.
AB  - Lindgren multiple funnel traps were set up in pine forests of central Oregon to
      determine the response of scolytid bark beetles to ethanol and 4-allylanisole
      (4AA). Traps were baited with two release rates of ethanol (4.5 or 41.4 mg/hr)
      and three release rates of 4AA (0, 0.6, or 4.3 mg/hr) in a 2 x 3 factorial
      design. All traps also released a 1:1 mixture of alpha- and beta-pinene at 11.4
      mg/hr. Of 13,396 scolytids caught, Dendroctonus valens made up 60%, Hylurgops
      spp. 18.5%, Ips spp. 16%, Hylastes spp. 1.8%, Ganthotrichus retusus 0.9%, and
      bark beetle predators another 2.8%. Increasing the release rate of ethanol in the
      absence of 4AA increased the number of most scolytid species caught by 1.5-3.7
      times, confirming its role as an attractant. Ips latidens, Temnochila chlorodia,
      and clerid predators were exceptions and did not show a response to higher
      ethanol release rates. Release of 4AA at the lowest rate inhibited attraction of
      most scolytids, with a significant reduction in G. retusus, Hylastes macer, and
      Hylurgops porosus when compared to traps without 4AA. A high release rate of 4AA
      further inhibited responses for most beetles compared to low 4AA. Seven species
      were significantly deterred by high 4AA, including the latter three, and Hylastes
      longicollis, Hylastes nigrinus, Hylurgops reticulatus, and Ips latidens.
      Exceptions include Hylurgops subcostulatus, which was significantly attracted to
      both low and high 4AA, and I. pini, which was attracted to low and high 4AA in
      combination with low ethanol, but unaffected by either release of 4AA with high
      ethanol. Dendroctonus valens was significantly attracted to low 4AA and
      unaffected by high 4AA. Predators appeared to be less inhibited by 4AA than most
      bark beetles. Although 4AA can deter the attraction of some secondary bark
      beetles to ethanol in combination with alpha- and beta-pinene, this inhibition
      could be weakened for certain species by increasing ethanol release rates. 4
      Allylanisole may have some utility for managing the behavior of secondary bark
      beetles sensitive to this compound.

PMID- 11446295
TI  - Antitermitic activity of essential oils and components from Taiwania (Taiwania
      cryptomerioides).
AB  - Antitermitic activity of Taiwania (Taiwania cryptomerioides Hayata) against
      Coptotermes formosanus Shiraki was demonstrated in laboratory tests. Blocks of
      sapwood and heartwood from T. cryptomerioides exhibited antitermitic activity.
      Bioassays revealed that heartwood essential oil exhibited the highest
      antitermitic activity, followed by sapwood essential oil and then the n-C6H14
      soluble fraction when tested at 10 mg/g. The order of termite mortality of three
      compounds purified from n-C6H14 soluble extracts of heartwood was cedrol > alpha
      cadinol > ferruginol. The termite resistance of T. cryptomerioides wood can be
      attributed to the termiticidal activity of cedrol and alpha-cadinol.

PMID- 11446296
TI  - Tannins in Puccinellia arctica: possible deterrents to herbivory by Canada geese.
AB  - Urban populations of Canada geese, Branta canadensis, pose a nuisance problem
      throughout most of the eastern United States and in other parts of the United
      States and Canada. Puccinellia arctica is a species of arctic grass that is
      unpalatable to Canada geese on the North Slope of Alaska and may prove to be an
      effective long-term and nonlethal means of controlling the growing populations of
      urban Canada geese. A comparative study of the secondary metabolites of both P.
      arctica and Puccinellia langeana and Poa pratensis, two palatable grass species
      that Canada geese generally consume, revealed no significant differences.
      However, ellagitannin levels were higher in P. arctica than in the palatable
      grass species and may be contributing to its unpalatability to Canada geese.
      These results support the potential to use P. arctica in public areas to control
      geese intrusions.

PMID- 11446297
TI  - Release rates for pine sawfly pheromones from two types of dispensers and
      phenology of Neodiprion sertifer.
AB  - Comparisons of release rates, duration in the field, and catch efficiency of
      polyethylene and cotton roll dispensers for the sex pheromones of sawflies
      (Hymenoptera: Diprionidae) were conducted. The release rates of the Neodiprion
      sertifer (Geoffr.) and Diprion pini (L.) sex pheromones, the acetates of
      pentadecanol and (2S,3S,7S)-3,7-dimethyl (2S,3R,7R)-3,7-dimethyl-2-tridecanol
      from polyethylene dispensers were measured at different temperatures in the
      laboratory. The release rates for the substances depended on both the temperature
      and initial load in the vials. The catch from cotton rolls baited with 100
      micrograms of the acetate or propionate of 3,7-dimethyl-2-pentadecanol was
      compared to the catch from regularly renewed cotton rolls baited with 10
      micrograms of the same acetate. The catch was higher for the 100-microgram cotton
      rolls for, at most, 45 days, and there was no significant differences in catch
      between the acetate and the propionate. The catch in traps baited with
      polyethylene or cotton roll dispensers loaded with the acetate of 3,7-dimethyl-2
      pentadecanol was compared and showed that cotton roll traps mirrored the
      decreasing release of the substance rather than the actual flight activity. The
      length of the flight period of N. sertifer in Sweden, the Czech Republic, Italy,
      and Greece did not exceed 100 days in any of the countries. By adjusting the
      initial pheromone load of the polyethylene vials to the expected temperatures, it
      should be possible to get a constant and sufficiently high release rate during
      the entire flight period.

PMID- 11446298
TI  - Allelopathy, DIMBOA production and genetic variability in accessions of Triticum
      speltoides.
AB  - A screening was conducted to study the allelopathic potential of Australian-held
      accessions of Triticum speltoides. Of 26 accessions, four were found to inhibit
      root growth in the indicator species, lettuce (Lactuca sativa). The methanol leaf
      extracts of these accessions significantly reduced the root length of wild oat
      (Avena spp.). In all but one case, alellopathic accessions contained higher
      amounts of DIMBOA than did nonallelopathic accessions. Since some variation in
      allelopathic response was detected within lines, random amplified polymorphic DNA
      (RAPD) markers were used to estimate genetic diversity between and within the
      allelopathic accessions of Triticum speltoides L. The average genetic similarity
      between all possible pairs of selected accessions was found to be 55% and ranged
      from 44% to 88%. Comparison of DNA extracted from different single seedlings
      within the same accession revealed significant intraaccession genetic diversity
      (4-24%), although this was much less than that observed between accessions
      tested. This intraaccession diversity has significant implications for the
      selection of T. speltoides accessions in breeding or screening programs.

PMID- 11446299
TI  - Limitations of Folin assays of foliar phenolics in ecological studies.
AB  - We examined the response of the widely used Folin-Denis assay to purified tannins
      from 16 woody plant species and to three commercial polyphenol preparations often
      used as standards. The reagent's response to these chemical mixtures differed
      significantly among sources (tree species, commercial preparations) and sampling
      dates, even though the mixtures contained the same total dry weight of tannins.
      Response to commercial standards usually did not resemble response to actual
      plant tannin and produced estimates that differed from actual concentrations by
      as much as twofold. Species-based and seasonal differences in polyphenol
      composition are evidently responsible for these variable results. Reagents that
      depend on redox reactions, such as the Folin-Denis, do not produce reliable
      absolute or relative quantification of phenolics when different species or
      samples from different dates are compared, and use of commercial standards does
      not resolve this problem.

PMID- 11446300
TI  - Testing the effects of drying methods on willow flavonoids, tannins, and
      salicylates.
AB  - In this study, we compared the effects of several preservation methods on the
      secondary phenolics of the mature leaves of purple willow (Salix purpurea L.,
      salicaceae) with results obtained with fresh leaf analyses. Conventional freeze
      drying, in which the leaves were first frozen with liquid nitrogen and then
      placed in a freeze-dryer, produced substantial qualitative and quantitative
      changes in purple willow flavonoids and salicylates. Modified freeze-drying, in
      which leaves were put into a freeze-dryer without being prefrozen, gave
      concentrations that, for most secondary components, were comparable with those
      found in fresh leaves. Reducing the freeze-dryer chamber temperature hindered the
      decomposition of phenolics in prefrozen leaves and in leaves dried without
      prefreezing. Heat drying induced substantial changes in the composition of all
      phenolics, except for apigenin-7-glucoside. Vacuum drying at room temperature
      gave the highest concentrations for nearly all phenolics, while room-drying with
      desiccation gave results that were comparable with those obtained by fresh leaf
      analyses.

PMID- 11446301
TI  - (E4,Z9)-tetradecadienal, a sex pheromone for three North American moth species in
      the genus Saturnia.
AB  - The lepidopteran genus Saturnia has three representatives in North America, S.
      walterorum, S. mendocino, and S. albofasciata. (E4,Z9)-Tetradecadienal (E4,Z9
      14:Ald) was identified as a sex pheromone component for all three species by
      combinations of coupled gas chromatography-electroantennogram detection (GC-EAD),
      GC-mass spectrometry (MS), and field trials. In field trials, all three species
      were strongly attracted to (E4,Z9-14:Ald) as a single component. Small amounts of
      (Z)-9-tetradecenal (Z9-14:Ald) also were found in extracts of all three species,
      but blends of this compound with E4,Z9-14:Ald were no more attractive to male
      moths than E4,Z9-14:Ald alone. Extracts of pheromone glands of female S.
      walterorum occasionally contained a third, trace compound eliciting responses
      from male antennae in GC-EAD experiments, but this compound was not identified.
      It is suggested that the three species can use the same, single components as a
      sex attractant because the flight period of S. albofasciata (fall) is different
      than that of the other two species (spring), whereas the geographic distributions
      of S. mendocino and S. walterorum overlap over only small portions of their
      ranges. Furthermore, the latter two species readily hybridize, so there may be
      minimal fitness cost to cross-attraction.

PMID- 11446302
TI  - Can simultaneous inhibition of seedling growth and stimulation of rhizosphere
      bacterial populations provide evidence for phytotoxin transfer from plant
      residues in the bulk soil to the rhizosphere of sensitive species?
AB  - In order to demonstrate that allelopathic interactions are occurring, one must,
      among other things, demonstrate that putative phytotoxins move from plant
      residues on or in the soil, the source, through the bulk soil to the root
      surface, a sink, by way of the rhizosphere. We hypothesized that the
      incorporation of phytotoxic plant residues into the soil would result in a
      simultaneous inhibition of seedling growth and a stimulation of the rhizosphere
      bacterial community that could utilize the putative phytotoxins as a sole carbon
      source. If true and consistently expressed, such as relationship would provide a
      means of establishing the transfer of phytotoxins from residue in the soil to the
      rhizosphere of a sensitive species under field conditions. Presently, direct
      evidence for such transfer is lacking. To test this hypothesis, cucumber
      seedlings were grown in soil containing various concentrations of wheat or
      sunflower tissue. Both tissue types contain phenolic acids, which have been
      implicated as allelopathic phytotoxins. The level of phytotoxicity of the plant
      tissues was determined by the inhibition of pigweed seedling emergence and
      cucumber seedling leaf area expansion. The stimulation of cucumber seedling
      rhizosphere bacterial communities was determined by the plate dilution frequency
      technique using a medium containing phenolic acids as the sole carbon source.
      When sunflower tissue was incorporated into autoclaved (to reduce the initial
      microbial populations) soil, a simultaneous inhibition of cucumber seedling
      growth and stimulation of the community of phenolic acid utilizing rhizosphere
      bacteria occurred. Thus, it was possible to observe simultaneous inhibition of
      cucumber seedlings and stimulation of phenolic acid utilizing rhizosphere
      bacteria, and therefore provide indirect evidence of phenolic acid transfer from
      plant residues in the soil to the root surface. However, the simultaneous
      responses were not sufficiently consistent to be used as a field screening tool
      but were dependent upon the levels of phenolic acids and the bulk soil and
      rhizosphere microbial populations present in the soil. It is possible that this
      screening procedure may be useful for phytotoxins that are more unique than
      phenolic acids.

PMID- 11446303
TI  - Butyl acetate and yeasts interact in adhesion and germination of Botrytis cinerea
      conidia in vitro and in fungal decay of golden delicious apple.
AB  - Butyl acetate is a volatile aroma and flavor compound in apple. Conidia of three
      strains of Botrytis cinerea, a fungus that causes decay of apple fruit in
      postharvest storage, had greater adhesion to and greater germination on
      polycarbonate membrane filters on water inside sealed 500 cc glass jars that were
      injected with 4 microliters butyl acetate than conidia not so exposed. Conidial
      germination was highly correlated with conidial adhesion. The yeasts
      Sporobolomyces roseus and Cryptococcus laurentii, but not Saccharomyces
      cerevisiae, reduced the adhesion and germination promoting effect of butyl
      acetate. Conidia did not readily utilize butyl acetate as a food source, as shown
      by lack of tetrazolium violet reduction, whereas S. roseus and C. laurentii, but
      not S. cerevisiae did. Butyl acetate added to suspensions of conidia increased
      the electrical conductivity of the suspensions and increased the loss of 14C from
      14C-labeled conidia compared to conidia unexposed to butyl acetate. Uptake of
      [14C]glucose by conidia was not increased by butyl acetate. Wounds of Golden
      Delicious apples inoculated with conidia (strain F-J-4) in a dilute solution of
      butyl acetate had greater decay than unexposed wounds. S. roseus and C.
      laurentii, but not S. cerevisiae, added with the conidia decreased the incidence
      or size of decay. Results indicated that butyl acetate increased conidial
      adhesion, stimulating conidial germination, and some yeasts can reduce this
      effect.

PMID- 11446304
TI  - Comparison of detoxification enzyme mRNAs in woodrats (Neotoma lepida) and
      laboratory rats.
AB  - To understand how mammalian herbivores process plant secondary compounds, we
      examined differences in expression of biotransformation enzyme mRNAs among
      populations of wild woodrats (Neotoma lepida) and laboratory rats. We compared
      expression of mRNAs for 10 biotransforming enzymes in five families (CYP, mEH,
      QOR, GST, and UGT) by using Northern blot analysis. We found significant
      differences in eight of 10 mRNAs tested. We suggest that the differences in mRNA
      expression among populations of woodrats and laboratory rats may be due to
      differences in the secondary compound composition of their diets. Our results
      provide background for future studies of detoxification strategies in mammalian
      herbivores that combine pharmacological techniques with an ecological
      perspective.

PMID- 11446305
TI  - Associations of income with self-reported ill-health and health resources in a
      rural community sample of Austria.
AB  - OBJECTIVES: Three levels of health indicators (1) self-reported ill-health, (2)
      internal health resources, and (3) external health resources were analysed in
      relation to a four-category house-hold income distribution in order to describe
      possible social gradients. The particular aim of this study was to obtain
      information on the association of income data with self-reported ill-health.
      METHODS: This cross-sectional study was based on a health survey. The sample
      represents around 10% of the rural population of some communities in Styria,
      randomly selected from the population registry. Interview data was collected from
      3781 participants aged 15 years and older, 1559 males and 2222 females. RESULTS:
      The results show that individuals from lower house-hold income classes are
      disadvantaged with regard to indicators of ill-health, internal and external
      health resources. Overall, the link between low income and poor health is highly
      consistent within our data. CONCLUSIONS: Considering our results we conclude that
      internal and external health resources are as unequally distributed over income
      levels as health outcome indicators.

PMID- 11446306
TI  - Anxious and depressive symptoms in adolescents: epidemiological data of a large
      scale study in Dresden.
AB  - OBJECTIVES: The present large scale epidemiological study was designed to assess
      the prevalence of mental disorders in adolescents. METHODS: Two cross-sectional
      studies have been performed in adolescents in Dresden and the results of the
      examination of 627 high school and 485 secondary school students (mean age 15.5
      years) are presented. Self rating procedures like the Beck Depression inventory
      (BDI) and clinical interviews have been used to enhance validity. RESULTS: The
      results underline the high prevalence rates of anxiety and depression in
      adolescents. Up to 30% of the 9th and 10th grades students suffer from mental
      disorders or are at risk for the development of mental disorders. CONCLUSIONS:
      Therefore primary prevention of mental disorders is desirable.

PMID- 11446307
TI  - [Dementia, depression and activity of daily living as risk factors for falls in
      elderly patients].
AB  - OBJECTIVES: Falls among elderly are a well-recognised public health problem. The
      purpose of the present study was to explore the relation between dementia, number
      of depressive symptoms, activities of daily living, setting, and risk of falling.
      METHODS: Data for the analysis came from a cross-sectional study about dementia,
      depression, and disabilities, carried out 1995/96 in Zurich and Geneva. The
      random sample stratified, by age and gender consisted of 921 subjects aged 65 and
      more. The interview was conducted by means of the Canberra interview for the
      Elderly, extended by short questionnaire. The subject was classified as a faller
      if the subject and/or the informant had reported a fall within the last 12 months
      prior to the interview. Logistic-regression analysis was used to determine the
      independent impact of dementia, depressive symptoms, and ADL-score on risk of
      falling. RESULTS: The stepwise logistic regression analysis has revealed a
      statistically significant association between dementia (OR 2.14, 95% CI 1.15
      3.96), two resp. three depressive symptoms (OR 1.64, 95% CI 1.04-2.60) as well as
      four or more depressive symptoms (OR 2.64, 95% CI 1.39-5.02) and the risk of
      falling. There was no statistically significant relationship between studied risk
      factors and the risk of being one-time faller. However, we found a strong
      positive association between dementia (OR 3.92, 95% CI 1.75-8.79), four or more
      depressive symptoms (OR 3.90, 95% CI 1.55-9.83) and the risk of being recurrent
      faller. Moreover, residents of nursing homes (OR 8.50, 95% CI 2.18-33.22) and
      elderly aged 85 or more (OR 2.29, 95% CI 1.08-4.87) were under statistically
      significant higher risk of sustaining recurrent falls. CONCLUSIONS: The results
      of the present study confirm that dementia and depression substantially increase
      the risk of falling.

PMID- 11446308
TI  - Setting up a quality assurance programme at the medical emergency department of a
      university hospital: promises and limitations.

PMID- 11446309
TI  - [The new subject catalog "Medical Psychology and Medical Sociology"].

PMID- 11446310
TI  - What is health? How do we measure health?

PMID- 11446311
TI  - Global public health: a challenge for the 21st century.

PMID- 11446312
TI  - Cohort studies: history of the method. I. Prospective cohort studies.
AB  - The term "cohort study" was introduced by Frost in 1935 to describe a study that
      compared the disease experience of people born at different periods, in
      particular the sex and age specific incidence of tuberculosis and the method was
      extended to the study of non-communicable disease by Korteweg who used it 20
      years later to analyse the epidemic of lung cancer in the Netherlands. Such
      studies are now best described as generation studies or generation cohort studies
      to distinguish them from the common type of study that is now carried out that
      consists in defining groups of individuals distinguished by some variable (such
      as place of residence, occupation, behaviour, or environmental exposure) and
      following them up to see if the incidence or mortality rates vary with the
      selected variable. This type of study is now one of the most important tools for
      epidemiological investigation. Initially called prospective studies, because the
      information characterising the individuals in the cohorts was recorded before the
      onset of disease, they are now preferably called cohort studies and distinguished
      as prospective cohort studies, If the information obtained relates to the
      subjects at the time the study is started and they are then followed, or
      retrospective cohort studies, if the information characterising the individuals
      was recorded sometime in the past (for example, the receipt of radiotherapy, or
      entry to a specific occupation). Studies of either type have the great advantage
      that they avoid all the most important sources of bias that may affect case
      control-studies, but the disadvantage that because incidence rates and more
      specifically mortality rates are commonly low, large numbers of subjects have to
      be followed for several (if not many) years to obtain statistically significant
      results. Several early prospective studies are described: Namely, those of 34,000
      male British doctors, 190,000 male and female American citizens with different
      smoking habits, some 5,000 middle aged residents of Framingham with different
      blood pressures, blood cholesterol levels, etc, and 13,000 children born in the
      UK in one week in 1946 with different family backgrounds.

PMID- 11446313
TI  - [Subject health concepts and health-related quality of life--is there a
      correlation?].
AB  - OBJECTIVES: The aim of this study was to explore associations between lay
      concepts of health, quality of life and the health-related evaluation of daily
      activities. METHODS: A total of 221 persons (patients from general practice and
      adult as well as young members of sporting clubs) participated in the study
      (response rate: 84%). RESULTS: Health was often defined as "highest value of
      life"; "normal functioning of body and soul" and "complete well-being". Many
      persons considered sports, sleeping and leisure time being highly important for
      their health. The single dimensions of quality of life were associated with some
      health-related evaluations of daily activities, e.g., bodily functioning and
      health-related evaluation of television. Dividing the sample into persons who did
      or did not consider a certain concept of health (e.g., well-being) to be highly
      important had the following consequences: The quality of life was associated with
      different evaluations of daily activities in different strata; this association
      was sometimes negative, sometimes positive in different strata; more variance was
      explained by dividing the sample into different strata. CONCLUSIONS: The often
      contradictory associations between evaluation of everyday activities, lay
      concepts of health and quality of life should warn us not to think of health
      concepts and health actions in form of linear relations. Rather, health promotion
      should be more stronger oriented towards the individual's life conditions and his
      or her attitude to health.

PMID- 11446314
TI  - [A hospital suited version of the German SF-36 and its psychometric comparison
      with the original questionnaire].
AB  - OBJECTIVES: The application of the Short-Form 36 Health Survey (SF-36) in
      hospitals is sometimes problematic, because some formulations like "at work" or
      "at home" in some items are not adequate in a hospital context. To account for
      this problem, we deleted 23 words like "at work" and "at home" from the SF-36 and
      generated thus a slightly modified version, the SF-36 m. The present paper deals
      primarily with two questions: is the SF-36 m well applicable in hospitals and is
      it still equivalent with the original version? METHODS: The SF-36 m was applied
      in more than 300 patients in two different hospitals. In one hospital a
      randomised design was used to assess the equivalence of SF-36 and SF-36 m before
      treatment. RESULTS: The reported high percentages of missing values in four
      critical scales were no more observed, when the SF-36 m was applied at the end of
      hospital stays. Only minor differences between SF-36 and SF-36 m with effect
      sizes < 0.20 were observed, although the scale "physical role function" and
      especially item 4d showed unexpectedly significantly higher values in the SF-36 m
      (p < 0.10). Additionally, higher and significant differences were observed
      between the applications of the questionnaires at home and in the hospital.
      CONCLUSIONS: Opposed to the original SF-36 the SF-36 m is well applicable at the
      end of hospital stays. SF-36 and SF-36 m show only minor differences in the
      comparison of their equivalence. The application of SF-36 and SF-36 m in
      hospitals seems to yield more favourable scores of health related quality of life
      than the application at home.

PMID- 11446315
TI  - [The value of qualitative regression grading as a prognostic factor for survival
      after preoperative radiochemotherapy in patients with advanced head and neck
      cancer].
AB  - BACKGROUND: Multimodal therapeutic strategies gain importance in locally advanced
      squamous cell carcinoma of the head and neck. Quantitative regression grading can
      be traced as an independent prognostic parameter in the histological examination
      in many neoadjuvantly treated cancers. Various regression systems have been
      suggested. We propose an easy to apply and economical score that seems to have a
      significant prognostic value in squamous cell carcinoma of the head and neck.
      PATIENTS AND METHODS: 43 patients with Stage IV squamous cell carcinoma of the
      head and neck have been treated neoadjuvantly with two cycles chemotherapy
      (ifosfamide 1.5 g/m2 day 1-5 with mesna [300 mg/m2], cisplatin 60 mg/m2 day 5,
      second cycle day 22). Hyperfractionated accelerated radiotherapy (30 Gy) was
      given from day 29 on. We divided the resected tumors histologically as follows:
      Grade I--no tumor cells to be identified, Grade II--necrosis, Grade III--partial
      destruction of the carcinoma, Grade IV--vital carcinoma. RESULTS: After 1 year
      the overall survival amounted to 79%, after 2 years 56%. A significant
      correlation could be established between qualitative tumor regression and
      survival. The 1-year survival depended on the regression of the primary as
      follows: 94% in Grade I, 80% in Grade II, 60% in Grade III and 56% in Grade IV.
      For the 2-year survival: 76%, 40%, 40%, 11% (p < 0.01). The results were similar
      regarding the neck dissections. CONCLUSIONS: After radiochemotherapy the
      histological regression is a significant prognostic factor of survival. A simple
      system with four subgroups is suggested which seems to be of a high prognostic
      value. We discuss to intensify the treatment for patients with good regression
      after neoadjuvant therapy for a further reduction of recurrence.

PMID- 11446316
TI  - Prognostic factors in glioblastoma multiforme. 10 years experience of a single
      institution.
AB  - BACKGROUND: To analyze prognostic factors in patients with a glioblastoma
      multiforme treated in an academic institute over the last 10 years. PATIENTS AND
      METHOD: From 1988 to 1998, 198 patients with pathologically confirmed
      glioblastoma multiforme were analyzed. Five radiation schedules were used mainly
      based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an
      interstitial iridium-192 (Ir-192) boost for selected patients with a good
      performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good
      performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions
      for poor prognostic patients and 5. no irradiation. RESULTS: Median survival was
      16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated
      with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively.
      No significant improvement in survival was encountered over the last 10 years. At
      multivariate analysis patients treated with a hypofractionated scheme showed a
      similar survival probability and duration of palliative effect compared to the
      conventionally fractionated group. The poor prognostic groups receiving
      radiotherapy had a highly significant better survival compared to the no
      treatment group. Patients treated with an Ir-192 boost had a better median
      survival compared to a historical group matched on selection criteria but without
      boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was
      similar. Analysis on pretreatment characteristics at multivariate analysis
      revealed age, neurological performance, addition of radiotherapy, total
      resection, tumor size post surgery and deterioration before start of radiotherapy
      (borderline) as significant prognostic factors for survival. CONCLUSION: Despite
      technical developments in surgery and radiotherapy over the last 10 years,
      survival of patients with a glioblastoma multiforme has not improved in our
      institution. The analysis of prognostic factors corresponded well with data from
      the literature. A short hypofractionated scheme seems to be a more appropriate
      treatment for patients with intermediate or poor prognosis as compared to a
      conventional scheme. The benefit in median survival for patients treated with an
      interstitial boost is partly explained by patient selection. Since there were no
      long-term survivors with this boost treatment, its clinical value, if there is
      one, is still limited.

PMID- 11446317
TI  - [Osteoradionecrosis after radiotherapy for gynecologic tumors].
AB  - AIM: Insufficiency fractures of the pelvis are a well known but rare and
      frequently misinterpreted radiation sequela. The clinical features and possible
      risk factors were investigated. PATIENTS AND METHODS: 71 of living 82 patients,
      who were treated 1986-1994 for gynecologic tumors were clinically examined. 47
      patients underwent also bone scan, CT of the pelvis and 13 patients had
      osteodensitometry. All patients had been treated with adjuvant (n = 29) or
      curative intent (n = 18) by d.v. fields with 18-MV photons, with 46 Gy in 23
      fractions plus brachytherapy (15-39 Gy). Median follow-up was 36 months. RESULTS:
      Seven patients developed pelvic insufficiency fractures 11 months (median,
      minimum 2 months) after treatment. All patients complained of moderate to severe
      pelvic pain, which resolved after 5-28 months without specific therapy in five of
      seven patients. At first examination all but one bone scan showed extremely
      increased uptake in the os sacrum and/or iliosacral joints, correlating CT scans
      demonstrated small fractures and bony destruction. Four of the asymptomatic 40
      patients with complete radiologic examinations had medium uptake in bone scan (CT
      normal). Three of four examined patients with insufficiency fractures and seven
      of nine patients without insufficiency fractures had osteoporosis. CONCLUSION: In
      women who present with pelvic pain after radiotherapy for gynecologic tumors bony
      destruction and fractures may be indicative of a late radiation effect rather
      than osseous metastasis, even after early onset of symptoms.

PMID- 11446318
TI  - [Veno-occlusive liver disease after total infradiaphragmatic lymphoid
      irradiation. A rare complication].
AB  - BACKGROUND: Radiotherapy is potentially curative in early stages of follicle
      center lymphoma. Frequent side effects are pancytopenia, nausea and abdominal
      discomfort. A radiation-induced liver injury with serious clinical symptoms and
      changes in liver function is a rare complication. CASE REPORT: Whole abdomen was
      irradiated in a 49-year-old patient with a centrocytic-centroblastic lymphoma,
      stage IA (localization: left inguinal region). A total dose of 30 Gy was
      delivered in a weekly fractionation of five times 1.5 Gy. Kidneys were protected
      by shielding after a dose of 13.5 Gy, liver blocks were positioned after 25 Gy.
      During the last 2 days of therapy the patient presented with weight gain,
      ascites, dyspnoea and elevated liver enzymes. Diagnostics revealed
      hepatosplenomegaly, ascites and an increased portosystemic pressure gradient.
      Liver biopsy specimen showed a veno-occlusive disease. Complete relief of
      symptomatology was achieved within 7 days following placement of a transjugular
      intrahepatic portosystemic stent-shunt (TIPSS), heparinization and diuretics.
      Liver enzymes are in the normal range. CONCLUSION: Veno-occlusive disease of the
      liver (VOD) is a very rare side effect of primary abdominal irradiation of
      follicle center lymphoma. This complication should be taken into consideration if
      a patient presents with upper right quadrant pain, ascites and elevation of liver
      enzymes especially within 4 months following radiotherapy. Genesis of veno
      occlusive disease, diagnostics, therapy and a review of the literature are
      presented.

PMID- 11446319
TI  - Postoperative radiotherapy of NSCLC--outcome after 3-D treatment planning.
AB  - AIM: To evaluate the benefit of postoperative radiotherapy depending on lymph
      node involvement in non-small-cell lung cancer (NSCLC). PATIENTS AND METHOD:
      Retrospective analysis of patients with NSCLC, who have been treated at the
      University of Giessen between 1986 and 1996 by surgery (n = 437) or surgery and 3
      D planned postoperative radiotherapy with 50-60 Gy (n = 115). Evaluation of
      survival rates and risk of death depending on postoperative radiotherapy taking
      into account N-category, tumor stage, completeness of resection and performance
      status. RESULTS: With individually 3-D planned postoperative radiotherapy there
      was a lower risk of death in all stages with lymph node metastases. The relative
      risks of death and the 95% CI were in pN1 0.64 (0.39-1.03), in pN2 0.31 (0.18
      0.56) and in pN3 0.25 (0.10-0.64). CONCLUSION: Our results suggest that the risk
      of death in NSCLC with lymph node involvement can be reduced by individually 3-D
      planned postoperative radiotherapy.

PMID- 11446320
TI  - [Radiotherapy planning for paraspinal tumors with CT-myelography].
AB  - BACKGROUND AND AIM: Artifacts due to metal implants are an important problem in
      diagnostic radiology and radiotherapy planning in tumors such as chordoma of the
      spine. A strict differentiation between target and radiosensitive structures e.g.
      spinal cord is absolutely essential for high-dose radiotherapy. Up to now CT and
      MRI techniques have provided only limited image quality in such situations. We
      introduce an approach to facilitate segmentation by using the technique of CT
      myelography for radiation treatment. PATIENT AND METHOD: A 48-year-old woman with
      multiple inoperable relapses of a chordoma in the lumbar spine and extensive
      metal instrumentation in this area was given to radiotherapy using IMRT-technique
      (intensity modulated). MRI- and CT-planning images did not allow differentiation
      between myelon, cauda equina, dural sac and tumor. In this situation we performed
      a CT-myelography with the patient in treatment position. RESULT: CT-myelographic
      images enabled precise differentiation between myelon, cauda equina and
      intraspinal tumor. A substantial improvement of the segmentation of the spinal
      cord was obtained. There was no compression of the dural sac along the spine.
      This information provided the basis for a precise radiotherapy planning in IMRT
      technique. CONCLUSION: In situations where CT- and MRI-techniques are not able to
      generate precise images which allow differentiation between tumor, myelon and
      cauda equina because of metal artifacts, CT-myelography is a promising technique
      which may help the diagnostic radiologist and radiation oncologist in planning
      radiotherapy.

PMID- 11446321
TI  - [Radiosurgery for brain metastases of acoustic neurinoma].

PMID- 11446322
TI  - [Controversial treatment of brain metastases of small-cell lung cancer.
      Randomized comparison of chemotherapy alone and radiochemotherapy].

PMID- 11446323
TI  - [Irinotecan plus fluorouracil and folinic acid in metastatic colorectal cancer].

PMID- 11446324
TI  - [Additional biopsies improve the detection rate of prostate cancer].

PMID- 11446325
TI  - [Effectiveness and limitations of delayed or immediate radiotherapy after radical
      prostatectomy].

PMID- 11446326
TI  - [Abstracts from the symposium on molecular genetic aspects of the destruction,
      regeneration and functional disorders of cartilage in degenerative joint
      diseases. Bad Saarow, 2-3 June 2000].

PMID- 11446327
TI  - XXVII Nordic Congress of Clinical Chemistry. Bergen, Norway, June 4-8, 2000.
      Abstracts.

PMID- 11446328
TI  - Royal College of Physicians of Ireland. National scientific medical meeting. 6
      April 2001. Abstracts.

PMID- 11446329
TI  - NASPE. North American Society of Pacing and Electrophysiology. 22nd annual
      scientific sessions. May 2-5, 2001, Boston, Massachusetts. Abstracts and program.

PMID- 11446330
TI  - [Regional meeting of the Japanese Association for Thoracic Surgery. Japan, 2000.
      Abstracts].

PMID- 11446331
TI  - Proceedings of the 2nd national theme symposium on hepatitis B infection in
      India. Therapeutic options and prevention strategies. New Delhi, September 2 and
      3, 2000. Abstracts.

PMID- 11446332
TI  - Prevention and management of hepatitis B: global scenario.

PMID- 11446333
TI  - Surgical closure: optimizing healing through suture placement.

PMID- 11446334
TI  - Re: Spontaneous rupture of renal metastasis of hepatocellular carcinoma:
      management by emergency transcatheter arterial embolization.

PMID- 11446335
TI  - 1st joint meeting of the International Bone and Mineral Society and the European
      Calcified Tissue Society. June 5-10, 2001, Madrid, Spain. Abstracts.

PMID- 11446336
TI  - Royal Austalasian College of Surgeons. Annual scientific congress. Canberra, 6-11
      May 2001. Abstracts.

PMID- 11446337
TI  - XVIth Congress of the European Association of Urology. April 7-10, 2001, Geneva.
      Abstracts.

PMID- 11446338
TI  - Facility profile. Doctor's dream becomes a reality. Beaumont Heart Center, Royal
      Oak, Mich.

PMID- 11446339
TI  - Association of Veterinary Teachers and Research Workers. Current topics in
      Veterinary Science. 55th annual conference. Scarborough, UK, 9th-12th April,
      2001. Abstracts.

PMID- 11446340
TI  - The Pfizer Plenary Lecture. Food safety: have veterinary researchers a role to
      play?

PMID- 11446344
TI  - Abstracts of the 6th ECNP (European College of Neuropsychopharmacology) regional
      meeting. Naples, Italy, May 19-21, 2001.

PMID- 11446343
TI  - DNA methylation in breast cancer.
AB  - Like all cancers, breast cancer is considered to result in part from the
      accumulation of multiple genetic alterations leading to oncogene overexpression
      and tumor suppressor loss. More recently, the role of epigenetic change as a
      distinct and crucial mechanism to silence a variety of methylated tissue-specific
      and imprinted genes has emerged in many cancer types. This review will briefly
      discuss basic aspects of DNA methylation, recent advances in DNA
      methyltransferases, the role of altered chromatin organization and the concept of
      gene transcriptional regulation built on methylated CpGs. In particular, we
      discuss epigenetic regulation of certain critical tumor suppressor and growth
      regulatory genes implicated in breast cancer, and its relevance to breast cancer
      diagnosis, prognosis, progression and therapy.

PMID- 11446345
TI  - Extrinsic compression of the left atrium: an unusual complication of a type B
      aortic dissection.

PMID- 11446346
TI  - Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia
      in a patient with situs solitus dextrocardia.

PMID- 11446347
TI  - ESN (European Society for Neurochemistry) conference on: advances in molecular
      mechanisms of neurological disorders. 22-25 May 2001, Perugia, Italy. Abstracts.

PMID- 11446348
TI  - 11th European Congress on Obesity. 30 May-2 June 2001, Vienna, Austria.
      Abstracts.

PMID- 11446349
TI  - European Association of Cardiothoracic Anaesthesiologists. 16th annual meeting
      abstracts. Weimar, Germany, 16-19 May, 2001.

PMID- 11446350
TI  - 4th International Conference on Bipolar Disorder. June 14-16, 2001, Pittsburgh,
      Pennsylvania. Abstracts.

PMID- 11446351
TI  - Abstracts of the 7th Central European Lung Cancer Conference. Prague, Czech
      Republic, June 3-6, 2001.

PMID- 11446352
TI  - Abstracts of the ASRI (American Society for Reproductive Immunology) XXIst Annual
      Meeting. Chicago, Illinois, USA. June 9-12, 2001.

PMID- 11446353
TI  - Human helminth infections -- future research foci.

PMID- 11446354
TI  - Resisting resistance.

PMID- 11446355
TI  - The importance of strict patient definition in studies of malaria pathogenesis.

PMID- 11446356
TI  - New trends in parasitism in Bulgaria.

PMID- 11446357
TI  - Population migration and malaria: terms of reference.

PMID- 11446358
TI  - Abstracts of the 2nd Quebec International Symposium on Cardiopulmonary
      Rehabilitation. Quebec, Canada, June 6-8, 2001.

PMID- 11446359
TI  - [XVII Congress of the SENPE (Spanish Society of Parenteral and Enteral
      Nutrition). Granada, Spain, 23-25 May 2001. Abstracts].

PMID- 11446360
TI  - Clarithromycin resistance to Mycobacterium abscessus.

PMID- 11446361
TI  - Culture Borrelia burgdorferi.

PMID- 11446362
TI  - Trends in ciprofloxacin nonsusceptibility and levofloxacin resistance among
      Streptococcus pneumoniae isolates in North America.

PMID- 11446364
TI  - First World Congress on Fetal Origins of Adult Disease. February 2-4, 2001.
      Mumbai, India. Abstracts.

PMID- 11446363
TI  - Misidentifying Helicobacter cinadei.

PMID- 11446365
TI  - AIDS in Africa.

PMID- 11446366
TI  - [Anticonvulsant-induced rheumatism: does a possible role of carbamazepine exist?
      A clinical case with a 20-month follow-up].
AB  - The rheumatism induced by anticonvulsants has been described in literature mostly
      because of phenobarbital therapy. The possible onset of this clinical picture due
      to other antiepileptic drugs is unusual and not well defined. We report the case
      of a 87-year-old female, affected by partial seizures treated with carbamazepine
      for 20 years, who came to our observation for the onset of disturbances that
      clearly resemble the classic syndrome of rheumatism induced by barbiturates: the
      diagnostic hypothesis of a drug side effect was confirmed by the marked clinical
      improvement of the patient after carbamazepine was stopped and substituted by
      gabapentin.

PMID- 11446367
TI  - Gianotti-Crosti syndrome following immunization.

PMID- 11446368
TI  - Phakomatosis pigmentovascularis type IIB with neurologic abnormalities.

PMID- 11446369
TI  - An additional familial case of temporal triangular alopecia.

PMID- 11446370
TI  - 10th Congress of the International Headache Society. June 29-July 2, 2001. New
      York City, New York, USA. Abstracts.

PMID- 11446371
TI  - Molecular characteristics of four human Y-specific microsatellites (DYS434,
      DYD437, DYS438, DYS439) for poulation and forensic studies.
AB  - In this work we present results on DYS434, DYS437, DYS438 and DYS439 loci studied
      in three population samples from North Portugal (N: 69), Macao (N: 59) and
      Mozambique (N: 64). Gene and haplotype diversity values are presented and
      compared. Gene diversity values ranged from 0.0290 to 0.0620 for DYS434; 0.0615
      to 0.5959 for DYS437; 0.4906 to 0.6424 for DYS438; 0.5873 to 0.7038 for DYS439.
      The highest average gene diversity was found in Macao and the lowest in
      Mozambique. Haplotype diversity in North Portugal, Macao and Mozambique was
      calculated to be 0.925, 0.928 and 0.787, respectively. Allele and haplotype
      frequency distributions for all markers were compared between the three
      populations. At the haplotype level all the differences between pairs of samples
      were significant. Sequencing analysis was performed for all alleles found in the
      four loci. Identical flanking sequences were observed with most of the alleles
      differing only by the repeat number. However, two variations were found in allele
      10 of DYS438: one in a Macao sample presenting a TTTTA before the last TTTTC
      repetition and one in a Portuguese sample showing a base substitution (A/C) at
      position 7 downstream from the tandem repeat. A base substitution (C/T) at
      position 3 upstream from the repeat motif was also found in allele 14 of DYS437
      in a sample from Mozambique.

PMID- 11446372
TI  - Characterization of five tomato phospholipase D cDNAs: rapid and specific
      expression of LePLDbeta1 on elicitation with xylanase.
AB  - Phospholipase D (PLD, EC 3.1.4.4.) has been implicated in a variety of plant
      processes, including signalling. In Arabidopsis thaliana a PLD gene family has
      been described and individual members classified into alpha-, beta- and gamma
      classes. Here we describe a second PLD gene family in tomato (Lycopersicon
      esculentum) that includes three alpha- and two beta-classes. Different expression
      patterns in plant organs were observed for each PLD. In testing a variety of
      stress treatments on tomato cell suspensions, PLDbeta1 mRNA was found to rapidly
      and specifically accumulate in response to the fungal elicitor xylanase. The
      greatest increase was found 2 h after treatment with 100 microg m1(-1) xylanase
      (ninefold). In vivo PLD activity increased nearly threefold over a 1.5 h period
      of treatment. When the elicitor was injected into tomato leaves, PLDbeta1 mRNA
      accumulation peaked at 2 h (threefold increase), before decreasing to background
      levels within 72 h. Mutant, non-active xylanase was as effective as the active
      enzyme in eliciting a response, suggesting that xylanase itself, and not the
      products resulting from its activity, functioned as an elicitor. When
      chitotetraose was used as elicitor, no PLDbeta1 mRNA accumulation was observed,
      thus it is not a general response to elicitation. Together these data show that
      PLD genes are differentially regulated, reflecting potential differences in
      cellular function. The possibility that PLDbeta1 is a signalling enzyme is
      discussed.

PMID- 11446373
TI  - The value of pre-operative diagnostic procedures for cervical involvement in
      uterine corpus carcinoma.
AB  - OBJECTIVE: To assess the value of procedures for pre-operative diagnosis of
      cervical involvement of uterine corpus carcinoma. MATERIALS AND METHODS: Four
      diagnostic procedures, including cervical cytology, endocervical curettage (ECC),
      magnetic resonance imaging (MRI), and hysteroscopy, were performed for diagnosis
      of cervical involvement in 60 patients with uterine corpus carcinoma. The
      preoperative diagnosis based on results obtained using by each procedure was
      retrospectively compared with the diagnosis based on histological examination of
      surgical specimens. Data were analyzed according to the standard definition of
      sensitivity, specificity, positive predictive value and negative predictive
      value. RESULTS: Cervical involvement was confirmed in 18 patients (30%). ECC
      showed high sensitivity (90.9%) and specificity (88.9%). Cervical cytology showed
      high specificity (88.6%). MRI showed very high specificity (99.2%) and high
      sensitivity (88.5%) in cases with cervical stromal invasion. CONCLUSION: Cervical
      cytology and MRI are useful for excluding cervical involvement. ECC is useful for
      positive diagnosis. MRI may be useful for cases with stromal invasion. The use of
      a combination of several procedures is essential for obtaining an accurate
      diagnosis of cervical involvement in cases of uterine corpus carcinoma.

PMID- 11446374
TI  - Opsonic function and concentration of human serum ficolin/P35.
AB  - Collectins, C-type (Ca2+-dependent) animal lectins with both collagenous and
      carbohydrate recognition domains, function as opsonins against pathogens. We
      previously described an N-acetylglucosamine (GlcNAc)-binding lectin (ficolin/P35)
      with a collagen- and a fibrinogen-like sequence present in human serum. In this
      report we show that ficolin/P35 can serve as an opsonin and enhance the clearance
      of pathogens having surface GlcNAc. Ficolin/P35 bound to an Ra chemotype strain
      of Salmonella typhimurium (TV119) which has an exposed GlcNAc at the non-reducing
      termini of the polysaccharide. On the other hand, ficolin/P35 did not bind to
      LT2, a smooth type strain of S. typhimurium with additional O-polysaccharides
      covering GlcNAc. Ficolin/P35 enhanced the uptake of TV119 by monocytes or
      polymorphonuclear leukocytes but had no opsonic activity towards LT2. These
      results suggest that, like collectins, ficolin/P35 is a collagenous lectin which
      has a role in innate immunity against certain pathogenic organisms by acting as
      an opsonin. We prepared monoclonal antibodies against ficolin/P35 and developed
      an enzyme-linked immunosorbent assay (ELISA) for measuring ficolin/P35
      concentrations in humans. The mean serum concentration of ficolin/P35 from 130
      normal individuals was estimated to be 13.7 microg/ml.

PMID- 11446375
TI  - Recurrent Wegener's granulomatosis with subglottic granulation.
AB  - While following the course of patients with Wegener's granulomatosis (WG) in
      which it had been possible to achieve a remission, we encountered a patient in
      whom we observed granuloma formation in the subglottis. A tracheotomy was
      performed because of the risk of respiratory distress, and after that there was a
      recrudescence of the patient's WG. During the course of the above, the patient
      remained cANCA (anti-neutrophil cytoplasmis antibody with cytoplasmic pattern)
      negative. When these facts were considered, it appeared that when the lesions are
      localized and progressing gradually, cANCA positivity does not develop. While
      cANCA test has gradually become a powerful tool for the diagnosis of WG, a
      comprehensive physical examination to identify localized lesions, together with
      biopsy and histopathological examination, should allow the diagnosis of WG.

PMID- 11446376
TI  - Temporal bone pathology in Wegener's granulomatosis.
AB  - This study aimed to demonstrate the temporal bone histopathology of two cases of
      Wegener's granulomatosis in which the initial symptoms were profound hearing loss
      and facial nerve palsy respectively. The first case, a woman of 44, suffered
      profound hearing loss which was remarkably improved by steroid and
      cyclophosphamide treatment for a time, and which seemed to be caused by invasion
      from granulation tissue filled in the tympanic cavity. The second case was a 61
      year-old woman presenting with the facial nerve palsy. The bony canal of the
      horizontal portion of the facial nerve was destroyed due to granulation tissue
      which filled in the tympanic cavity, and granulomatous involvement was observed
      in the facial nerve. Wegener's granulomatosis can involve the middle ear and/or
      inner ear, causing hearing loss of conductive, mixed or sensorineural type.
      Pathogenesis of facial nerve palsy seems to be related to Wegener's granulomatous
      involvement of facial nerve, because the facial nerve palsy also resolved by
      using steroid and cyclophosphamide.

PMID- 11446377
TI  - Myxoid leiomyosarcoma of the uterus.
AB  - A 70-year-old, menopausal Japanese woman with large uterine tumor underwent total
      hysterectomy. Microscopic examination revealed a myxoid leiomyosarcoma with 5 to
      6 mitoses/10 high power field (HPF). Immunohistochemically, the tumor cells
      reacted with desmin, suggesting that they are derived from uterine smooth muscle
      cells. The patient was treated with the combination chemotherapy consisting of
      cisplatin, adriamycin and cyclophosphamide, and she has been free from disease
      for 70 months after the operation.

PMID- 11446378
TI  - Atypical Cogan's syndrome successfully treated with corticosteroids and pulse
      cyclophosphamide therapy.
AB  - An 18-year-old woman was admitted to the medical center near her home with
      complaints of high fever and severe headache in June 1995. A diagnosis of adult
      onset Still's disease was suspected and 50 mg/day of prednisolone was orally
      administered. In early April 1997, the patient suffered from sudden bilateral
      hearing loss and high fever. Pure tone audiogram taken at the same time showed an
      asymmetric bilateral neurosensorial hearing loss. A diagnosis of Cogan's syndrome
      was made. Administration of 60 mg prednisolone daily improved fever. Audiogram
      taken one month after administration of prednisolone showed improvement in the
      right ear. Monthly cyclophosphamide pulse therapy 700 mg combined with oral
      prednisolone was instituted. This combination therapy enabled the successful
      tapering of prednisolone without recurrence of hearing loss. Combined
      corticosteroid and pulse cyclophosphamide therapy would appear to be one
      effective regimen for Cogan's syndrome.

PMID- 11446380
TI  - European Society of Gynaecological Oncology. 12th international meeting. 21-24
      April 2001, Venice, Italy. Abstracts.

PMID- 11446379
TI  - Experience as a visiting scholar in Fukushima.
AB  - In this article, author summarizes the experience as a visiting scholar in
      Fukushima Medical University. The current status and technical innovations of
      living related liver transplantation in Japan are comprehensively evaluated. New
      approaches for islet transplantation in the laboratory of Prof. Gotoh and
      author's preliminary experience of the experimental islet xenotransplantation are
      also succinctly reported. In the meantime, the author emphasizes the importance
      of an "open" department and library in which there is a great difference by
      comparison with that in China. I had an opportunity to study as a visiting
      scholar in Fukushima Medical University from July 6th to Sept. 28th, 2000. Here,
      I summarize what I saw and learnt, which have left a deep impression on my memory
      in Fukushima.

PMID- 11446381
TI  - 72nd Congress of the European Atherosclerosis Society. Glasgow, 20-23 May 2001.
      Abstracts.

PMID- 11446382
TI  - Society for the Study of Fertility annual conference. University of Cambridge,
      July 2001. Abstracts.

PMID- 11446383
TI  - 11th Meeting of the European Association for the Study of Diabetic Eye
      Complications (EASDEC). Paris, France. May 18-20, 2001. Abstracts.

PMID- 11446384
TI  - Protein phosphorylation in Rhodnius prolixus oocytes: identification of a type II
      casein kinase.
AB  - A protein kinase activity in chorionated oocytes of Rhodnius prolixus
      phosphorylates in vitro vitellin (VT), the major yolk protein. Phosphatase
      inhibitors including NaF, sodium vanadate, beta-glycerophosphate and okadaic acid
      did not alter the protein phosphorylation profile to a visible extent. Among the
      exogenous protein substrates tested, casein was readily phosphorylated, but
      histones were not. Several different protein kinase activators, including cAMP,
      Ca2+ plus calmodulin, Ca2+ plus diolein and phosphatidylserine, were added to the
      reaction media but spermidine was the only effective one, inducing a 2-fold
      increase in the phosphorylation of VT. A strong inhibition was obtained with
      nanomolar levels of heparin. The enzyme could also accept GTP as the phosphate
      donor instead of ATP. These properties identify the major protein kinase activity
      as a type II casein kinase (CK II). The pH dependence and the effects of mono-
      and divalent cations on VT phosphorylation were also studied. Gel filtration
      revealed only one peak of protein kinase activity, with a molecular mass of 170
      K, similar to values previously reported in the literature for CK IIs from other
      organisms.

PMID- 11446385
TI  - Etanercept reduces hyperalgesia in experimental painful neuropathy.
AB  - Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein
      competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been
      successfully used in patients with rheumatoid arthritis, where it reduces pain
      and inflammation. Because locally produced proinflammatory cytokines play a role
      in pain after nerve injury, we investigated whether etanercept can reduce pain
      and hyperalgesia in an animal model of painful neuropathy, the chronic
      constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or
      sham treatment by local near-nerve injection to the injured nerve or by systemic
      application. Treatment with etanercept reduced thermal hyperalgesia and
      mechanical allodynia significantly in both modes of application. The effect of
      etanercept was present in animals that were treated from the time of surgery and
      in those that were treated from day 6, when hyperalgesia was already present.
      These results suggest the potential of etanercept as a treatment option for
      patients with neuropathic pain.

PMID- 11446386
TI  - Hyperbaric oxygen treatment has different effects on nerve regeneration in
      acellular nerve and muscle grafts.
AB  - Effects of hyperbaric oxygen treatment (HBO) on nerve regeneration in acellular
      nerve and muscle grafts were investigated in rats. Nerve and muscle grafts were
      made acellular by freeze-thawing and the obtained grafts were used to bridge a 10
      mm gap in the sciatic nerve on the left and right sides, respectively. Rats were
      treated with HBO (100% oxygen for 90 minutes at 2.5 atmospheres absolute pressure
      ATA) twice a day for 7 days. Axonal outgrowth, Schwann cell migration and
      invasion of macrophages were examined 10 days after the graft procedure by
      staining neurofilaments, S-100 proteins and the macrophage antibodies ED1 and
      ED2, respectively. Axonal outgrowth and Schwann cell migration in acellular nerve
      grafts were superior to that found in the acellular muscle grafts. However, there
      was no difference between HBO-treated and nontreated rats in acellular nerve
      grafts. Such a difference was found in acellular muscle grafts concerning both
      axonal outgrowth and Schwann cell migration from the proximal nerve end. No
      differences in the content of macrophages or neovascularization (alkaline
      phosphatase staining) in either of the grafts and treatments were seen. It is
      concluded that there is a differential effect of HBO-treatment in acellular nerve
      and muscle grafts and that HBO-treatment has no effect on the regeneration
      process in acellular nerve grafts, in contrast to fresh cellular nerve grafts
      where a beneficial effect has previously been reported.

PMID- 11446387
TI  - Histopathological features of X-linked Charcot-Marie-Tooth disease in 8 patients
      from 6 families with different connexin32 mutations.
AB  - There is still confusion as to whether X-linked Charcot-Marie-Tooth disease
      (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight
      symptomatic patients, 7 males and 1 female, from 6 families with identified
      connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative
      and ultrastructural studies were performed, and histopathological lesions in
      these 8 patients proved to be quite homogeneous. The myelinated fiber count was
      within normal values or only moderately decreased. In 7 cases, the distribution
      of myelinated fibers was unimodal due to a loss of large fibers, coexisting with
      numerous clusters of small regenerating fibers. At ultrastructural level, these
      clusters were often surrounded by flattened Schwann cell processes giving an
      aspect of "pseudo-onion bulb" formation. There was no "naked axon" (ie,
      demyelinated axon), and real "onion bulb" formations composed of flattened
      Schwann cell processes surrounding an isolated myelinated fiber were discrete and
      not numerous. Macrophages laden with myelin debris were scarce or absent in the
      endoneurium. Several fibers appeared discretely hypomyelinated and the calculated
      g-ratio was scarcely higher than the mean control value. Lesions of unmyelinated
      fibers were absent in 7 cases and mild in one. Given that the primary defect
      concerns connexin32, we think that the histopathological features observed in our
      patients correspond to primary hypomyelination rather than to ongoing
      demyelination. The associated axonal degeneration might be secondary to defective
      axon-Schwann cell interactions.

PMID- 11446388
TI  - Establishment and characterization of immortalized Schwann cells from murine
      model of Niemann-Pick disease type C (spm/spm).
AB  - Niemann-Pick disease type C (NPC) is characterized by an accumulation of
      unesterified cholesterol in the endosomal/lysosomal (E/L) system, resulting in
      progressive neurodegeneration and death during early childhood. To investigate
      the cellular pathomechanism of nervous system involvement in NPC, continuous
      neural cell lines are desirable. In this study, we obtained neuronal and Schwann
      cell cultures and established spontaneously immortalized Schwann cell lines from
      dorsal root ganglia and peripheral nerves of NPC model mouse (spm/spm). One of
      the cell lines, designated SPMS9, had distinct Schwann cell phenotypes and was
      maintained over 10 months without phenotypic alterations. The level of Npc1 mRNA
      was markedly decreased, and NPC1 protein was not detectable in SPMS9 cells. These
      cells contained intracytoplasmic granules positive for filipin cholesterol
      staining and immunoreactive for GM2 ganglioside. Electron-microscopically,
      intracytoplasmic polymorphous membranous inclusions and vacuoles were
      demonstrated in SPMS9 cells. The treatment with an inhibitor of ceramide-specific
      glucosyltransferase, N-butyldeoxynojirimysin (NB-DNJ) markedly reduced the
      intracytoplasmic granular immunofluorescence for GM2 ganglioside in SPMS9 cells,
      whereas the amount of filipin-positive granules remained unchanged. The SPMS9
      cells retained vesicular fluorescence of cationic dye acriflavine 16-24 hours
      after loading, indicating the defect of transmembrane efflux pump activity of
      NPC1 in the E/L compartment in these cells. These immortalized Schwann cells can
      be useful in studies on the nervous system lesions in NPC.

PMID- 11446389
TI  - Focal myelin swellings and tomacula in anti-MAG IgM paraproteinaemic neuropathy:
      novel teased nerve fiber studies.
AB  - Focal myelin swellings and tomacula in teased nerve fibers from a case of IgM
      anti-myelin-associated glycoprotein (MAG) paraproteinaemic neuropathy were
      examined using a novel technique. Five different morphologic abnormalities were
      identified--myelin sheath outfolding, myelin sheath infolding, enlargement of the
      adaxonal space, myelin degeneration, multiple increased concentric loops--and a
      combination of these structural abnormalities often occur in association with
      myelin degeneration. Similar structural changes were found in externally normal
      segments of teased fibers without evidence of myelin swelling or tomacula from
      the same case. These structural abnormalities are consistent with a disturbance
      of the normal adhesion functions of MAG in the maintenance of axon-myelin
      relationships.

PMID- 11446390
TI  - Fighting invisible barriers to equitable health care. Interview by Patrick
      Mullen.

PMID- 11446391
TI  - Bile salt-stimulated lipase in the milk of Fulani and Kanuri women in Nigeria and
      native Nepalese women.
AB  - Human milk provides newborns with several physiologically important proteins not
      found in cow's milk, including bile salt-stimulated lipase (BSSL) that
      compensates for the reduced lipolytic capability of the newborn intestine. We
      analyzed the milk of two ethnically distinct groups of women in northern Nigeria
      and Nepal. The milk of the Nepalese women (n = 36) contained slightly more BSSL
      activity (mean, 38.8 units/mL) than that of Fulani (n = 48; mean, 30.3 units/mL)
      and Kanuri (n = 90; mean 27.6 units/mL) women in Nigeria. There was also a weak
      positive correlation between the BSSL content of the milk and the body mass index
      (BMI) of the lactating women. The BSSL activity declined with the length of
      lactation for both well-nourished and undernourished women. The presence of a
      heat-stable inhibitor of BSSL in cow's milk was also demonstrated. This finding,
      along with the decrease in BSSL activity postgestation, could be of significance
      to populations such as the Fulani of the western Sahel who supplement the diets
      of their infants with unpasteurized cow's milk.

PMID- 11446392
TI  - Familial adenomatous polyposis: a case report and review of the literature.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant condition
      characterized by diffuse intestinal polyposis, specific gene mutation, and
      predisposition for developing colon cancer. Left untreated, patients with FAP
      will develop colorectal carcinoma during early adulthood. Hence, early detection
      and surgical intervention are of the utmost importance. Colectomy is required and
      may include an ileal pouch with ileoanal anastomosis, which eliminates the colon
      and rectal disease while preserving fecal continence and avoidance of a permanent
      ileostomy. Advances in the treatment of FAP with associated reduction in
      mortality from colorectal carcinoma make extracolonic manifestations of the
      disease more common and life-long surveillance is mandatory. The most life
      threatening extracolonic manifestations of FAP are periampullary carcinoma and
      desmoid tumors. The upper gastrointestinal tract should be monitored
      endoscopically at the time of diagnosis and assessed regularly thereafter.
      Duodenal adenomas should be resected so as to avoid the devastating effects of
      invasive periampullary carcinoma. Additionally, the development of desmoid tumors
      needs to be monitored (by CT or MRI), so as to avoid the severe complications of
      local invasion. Further research is indicated in the development of effective
      screening and treatment for this condition.

PMID- 11446393
TI  - Survival patterns among HIV+ individuals based on health care utilization.
AB  - The purpose of this study was to determine if HIV+ persons who first obtained
      health care in New Orleans through public hospital inpatient services had a
      higher risk of death or disease progression than patients who first entered care
      through public outpatient services. The sites included the largest HIV outpatient
      clinic in the Gulf South, two early intervention sites and a public hospital. A
      medical record review on patients who attended these sites from July 1995 through
      December 1999 and were enrolled in the Adult Spectrum of Disease (ASD) Study was
      conducted (n = 3402). The multivariate analysis examined the associations between
      inpatient services and the main effects. Kaplan-Meier analysis and Cox
      proportional hazards regression were performed. Risk of death or disease
      progression was analyzed for three different endpoints: time from study entry to
      death, time from HIV to AIDS, and time from AIDS to death. The multivariate
      analysis showed that patients first entering care through inpatient services were
      significantly more likely to be African American, have AIDS, and use drugs. The
      risk of death or disease progression was significantly higher for all three
      endpoints. Results from this study indicate that HIV+ individuals receiving
      initial care through public hospital inpatient services may require more
      effective early intervention.

PMID- 11446394
TI  - Legionella micdadei lung abscess in a patient with HIV-associated nephropathy.
AB  - A patient with end-stage renal disease due to human immunodeficiency-associated
      nephropathy developed fever, cough and chest pain over a week's duration. He was
      diagnosed with lung abscess and started on antibiotic coverage. He underwent
      bronchoscopy because of progression of his illness and persistent fever and
      bronchoalveolar lavage culture isolated Legionella micdadei. In spite of
      appropriate antibiotic therapy, the patient remained febrile for 10 days,
      necessitating chest tube drainage. After a 6-week course of antibiotics and
      drainage, the patient made an uneventful recovery. Infections due to L. micdadei
      may be hard to diagnose because of difficulties in isolating this bacteria.

PMID- 11446395
TI  - Eikenella corrodens: an unusual cause of severe parapneumonic infection and
      empyema in immunocompetent patients.
AB  - Over the past 25 years, Eikenella corrodens has increasingly been recognized for
      its pathogenic potential. Previously identified as an organism most likely to
      cause opportunistic infection in the immunocompromised host, Eikenella more
      recently has been implicated in a number of clinical infections in non
      immunocompromised patients. We report a case of community-acquired pneumonia,
      caused by Eikenella, in a patient with diabetes mellitus and a past history of
      testicular cancer. A review of the literature was conducted in order to review
      other cases of pulmonary infection with Eikenella, in immunocompetent adults. The
      condition was diagnosed in 15 patients, occurring most often in men with a mean
      age of 50. Patients most often presented with fever, cough and pleuritic chest
      pain. Complications often involved parapneumonic effusion, empyema, and necrotic
      parenchymal disease. Mortality rates appear to be low. Eikenella is most often
      susceptible to ampicillin and has variable susceptibility to aminoglycosides. The
      addition of clindamycin in non-immunocompromised patients with Eikenella
      infection, co-infected with other pathogens, also appears to be useful. Surgical
      intervention plays an important role in the recovery of these patients.

PMID- 11446396
TI  - Prescription for change: health supplement regulations and protecting the public
      interest.

PMID- 11446397
TI  - A biocultural investigation of the weanling's dilemma in Kathmandu, Nepal: do
      universal recommendations for weaning practices make sense?
AB  - The primary objective of this report is to use data from a study of infant growth
      and weaning practices in Kathmandu, Nepal, to investigate universal
      recommendations about exclusive breast-feeding up to 6 months postpartum. A
      secondary objective is to demonstrate the complexity of the biocultural nature of
      infant feeding practices. A sample of 283 children under 5 years of age and their
      228 mothers living in a peri-urban district of Kathmandu participated in this
      study. The children's height/length and weight were measured three times over 9
      months. At each session, a demographic, child health and infant feeding survey
      was administered; between sessions, in-depth interviews were conducted with
      mothers regarding infant feeding practices. While a few of the infants under 2
      months were receiving non-breast milk foods, at 3 months of age half of the
      sample had been introduced to non-breast milk foods and by 7 months all infants
      were eating non-breast milk foods. A comparison of growth indices and velocities
      between exclusively and partially breast-fed infants from birth to 7 months of
      age shows no evidence for a difference in nutritional status between the two
      groups. Although there are cultural rules about breast-feeding that vary by
      ethnic group, all mothers followed a feeding method that depended on their
      assessment of whether the child was getting enough breast milk. The conclusion is
      that exclusive breast-feeding up to 6 months may not be appropriate for all
      infants. In this sample, breast-feeding duration is not shortened by the early
      introduction of non-breast milk foods, as the median age of breast-feeding
      cessation is 36 months. One of the main reasons for severance was the onset of
      another pregnancy. Investigation of infant feeding practices must be
      contextualized in the local ecology of the population. While cultural beliefs
      about breast-feeding are relevant, mothers' individual assessments of their
      children's nutritional needs and demographic events in parents' lives must also
      be considered.

PMID- 11446398
TI  - Understanding users' perspectives of barriers to maternal health care use in
      Maharashtra, India.
AB  - This paper uses data collected using in-depth, semi-structured interviews to
      examine utilization of maternal health care services among two rural and urban
      populations of Pune and Mumbai in Maharashtra, India. The study aims to identify
      key social, economic and cultural factors influencing women's decisions to use
      maternal health care and the places used for child delivery, whilst considering
      the accessibility of facilities available in the local area. Socioeconomic status
      was not found to be a barrier to service use when women perceived the benefits of
      the service to outweigh the cost, and when the service was within reasonable
      distance of the respondent's place of residence. A large number of women
      perceived private services to be superior to those provided by the government,
      although cost often meant they were unable to use them. The provision of services
      did not ensure that women used them; they had to first perceive them to be
      beneficial to their health and that of their unborn child. Respondents identified
      the poor quality of services offered at government institutions to be a
      motivating factor for delivering at home. Thus further investigation is needed
      into the quality of services provided by government facilities in the area. A
      number of respondents who had received antenatal care went on to deliver in the
      home environment without a trained birth attendant. Further research is needed to
      establish the types of care provided during an antenatal consultation to
      establish the feasibility of using these visits to encourage women, particularly
      those with high-risk pregnancies, to be linked to a trained attendant for
      delivery.

PMID- 11446399
TI  - Natural selection at the MJD locus: phenotypic diversity, survival and fertility
      among Machado-Joseph Disease patients from the Azores.
AB  - Machado-Joseph Disease (MJD) is an autosomal dominant neurodegenerative disorder
      of adult onset, associated with the expansion of a (CAG)n tract in the coding
      region of the causative gene, localized on 14q32.1. Machado-Joseph Disease shows
      non-Mendelian features typical of other triplet repeat disorders, including
      clinical heterogeneity, variable age at onset and anticipation. Three phenotypes
      have been proposed (clinical types 1, 2 and 3). Type 1 is associated with early
      age at onset and a high repeat number of the CAG sequence, and Types 2 and 3 have
      later onset and lower numbers of CAG repeats. This paper investigates whether
      there is selection against the MJD gene, acting through differential survival.
      nuptiality and fertility associated with clinical type and age at onset. The
      study sample comprised 40 MJD patients from the Azores (Portugal) having fully
      documented reproductive histories and known dates of death. The proportion of
      married patients of each clinical type increased from 0.22 among Type 1 patients,
      to 0.40 in Type 2 and 0.95 in Type 3. Age at onset and length of survival were
      also associated with marital status, with the married cases having later mean age
      at onset and longer mean survival time. In the whole sample, clinical type was
      associated with fertility, with significantly fewer children born to Type 1
      patients. Among married patients clinical type was not associated with age at
      marriage, reproductive span or number of children. No reduction of fertility was
      detected among married patients in whom the onset of MJD was below the age of 50.
      The authors' interpretation of these results is that the high-repeat CAG
      haplotypes associated with early age at onset and clinical Type 1 are selected
      against through reduced survival and fertility. The fertility component of
      selection is mediated by nuptiality rather than marital fertility.

PMID- 11446400
TI  - Analysis of factors associated with maternal mortality in Kenyan hospitals.
AB  - This paper examines the association of the sociodemographic characteristics of
      women and the unobserved hospital factors with maternal mortality in Kenya using
      multilevel logistic regression. The data analysed comprise hospital records for
      58,151 obstetric admissions in sixteen public hospitals, consisting of 182
      maternal deaths. The results show that the probability of maternal mortality
      depends on both observed factors that are associated with a particular woman and
      unobserved factors peculiar to the admitting hospital. The individual
      characteristics observed to have a significant association with maternal
      mortality include maternal age, antenatal clinic attendance and educational
      attainment. The hospital variation is observed to be stronger for women with
      least favourable sociodemographic characteristics. For example, the risk of
      maternal death at high-risk hospitals for women aged 35 years and above, who had
      low levels of education, and did not attend antenatal care is about 280 deaths
      per 1000 admissions. The risk for similar women at low-risk hospitals is about 4
      deaths per 1000. To complement results from the analysis of individual patient
      records, the paper includes findings from hospital staff reports regarding the
      maternal mortality situation at the hospitals.

PMID- 11446401
TI  - Factors influencing low birth weight and prematurity in Botswana.
AB  - The purpose of this study was to investigate the socioeconomic, biological and
      behavioural factors influencing low birth weight and prematurity in Botswana.
      Data were from the Botswana Obstetric Record covering the years 1990 to 1995, and
      were analysed with both descriptive statistics and multivariate analysis. The
      study found that the major positive risk factors for low birth weight were: late
      and less frequent attendance of antenatal care services, having experienced
      pregnancy termination before, low or no education, unmarried motherhood and place
      of birth. With regard to prematurity, age, late and less frequent attendance of
      antenatal care services, unmarried motherhood and place of birth were found to be
      the major positive risk factors. The importance of early and regular antenatal
      care attendance, marriage and place of birth cut across both low birth weight and
      prematurity.

PMID- 11446402
TI  - Starting, spacing and stopping in the reproductive histories of outer Hebridean
      families.
AB  - Maternal ages at the first maternity (starting), at the last maternity (stopping)
      and the lengths of intervals between maternities (spacing) have been studied in
      the Outer Hebridean islands of Harris and Barra for births between the years of
      1855 and 1990, a period during which a considerable 'fertility transition'
      occurred. There was a tendency in each island for increases with time in the ages
      at starting among less-fecund women (although after 1936 starting ages declined),
      and highly significant heterogeneity of covariance: adjusted means dependent on
      the total numbers of maternities experienced. The same result was seen for the
      ages at stopping. Lengths of reproductive life (the difference between ages at
      starting and stopping) rose to 1876-1895, and then fell, apart from a short-lived
      rise in Barra during 1956-1975, possibly due to the papal encyclical Humaneae
      Vitae. Intervals between marriage and first maternity and between successive
      maternities were studied by hazard function survival analysis. The marriage first
      birth interval remained very constant, unaffected by total maternities. The
      father's occupation and the mother's age at first maternity showed no significant
      relationships. In Barra there was a weak negative relationship with the date of
      the marriage. For intervals between maternities in both islands, total
      maternities and the death of a previous infant were associated with shorter, and
      birth order with longer intervals. In Harris, there were tendencies for intervals
      to be consistently long or short in families, and for the age of the mother and
      date at first maternity to be negatively related to the length of the interval.
      In Barra, a previous multiple birth was followed by a longer interval. The date
      of the previous maternity, father's occupation, maternal age at the previous
      maternity, the sex of the previous child, and the duration of the marriage
      appeared to have no influence on maternity intervals. Evidence for an effect of
      economic deprivation during the 19th century on the variables considered was
      equivocal. During the 20th century, it is suggested that economic depression
      during the inter-war years, the spread of contraception, and improvements in
      health care may have acted 'synergistically' to produce the lower ages of
      childbearing and the shortening of maternity intervals and reproductive lives.

PMID- 11446403
TI  - Biodemographic study of a central Apennine area (Italy) in the 19th and 20th
      centuries: marriage seasonality and reproductive isolation.
AB  - This study investigates seasonality of marriages and reproductive isolation in
      six long-isolated communities in the central Apennines (Italy). It had two
      objectives: (1) the identification of an Apennine biodemographic model in
      comparison with mountain communities of other regions, and with non-Apennine
      communities in Abruzzo, and (2) to identify the possible effects of the drainage
      of Lake Fucino (1854-1876) on that area. Marriages in this region show two very
      stable seasonal patterns: one is typical of sedentary rural societies, with
      summer migrations and marriages preferentially celebrated in the winter, and the
      other has marriages that are strongly concentrated in the summer months, i.e.
      between 75% and 93.5% of marriages were celebrated between June and October in
      these communities in the 1800s. These were traditionally pastoral communities
      with winter transhumance of the flocks and their shepherds towards the lowlands
      of southern Italy. In both groups, restrictions imposed by the Catholic Church do
      not seem to have affected the timing of marriages. Indeed, economic factors
      related to work activities seem to have had more influence. Concerning
      reproductive isolation, the results show high rates of endogamy: between 85% and
      98% in both the 19th and 20th centuries. Rates of consanguineous marriages were
      between 5% and 20%, and those of isonymous marriages rarely exceeded 9%. The
      coefficient of inbreeding a shows that there was a delayed, limited period of
      increased consanguinity in the few decades around the turn of the century. This
      is different from the national situation, and thus could be a consequence of the
      Lake Fucino drainage.

PMID- 11446404
TI  - Birth weight, sexual orientation and the sex of preceding siblings.
AB  - This study's first objective was to compare the mean birth weights of homosexual
      and heterosexual men and women. Its second objective was to investigate whether
      prior male and female fetuses have different effects on the birth weight of
      subsequent fetuses. The subjects were 3229 adult men and women (the probands),
      who weighed at least 2500 g at birth, and whose mothers knew the sex of the child
      (or fetus) for each pregnancy prior to the proband. Information on birth weight,
      maternal gravidity and other demographic variables was reported on questionnaires
      completed by the probands' mothers. The results confirmed earlier reports that
      boys with older brothers weigh less at birth than boys with older sisters, but
      they did not confirm reports that girls with older brothers weigh less than girls
      with older sisters. The results did not show across-the-board differences in the
      mean birth weights of homosexual versus heterosexual women or homosexual versus
      heterosexual men. However, the homosexual males with older brothers weighed about
      170 g less at birth than the heterosexual males with older brothers. It is
      suggested that this pattern of results may reflect a maternal immune response to
      Y-linked minor histocompatibility antigens (H-Y antigens). According to this
      hypothesis, when the maternal immune response is mild, it produces only a
      slightly reduced birth weight, but when it is stronger, it produces a markedly
      reduced birth weight as well as an increased probability of homosexuality.

PMID- 11446405
TI  - Group differences in mean intelligence for the Dutch and Third World immigrants.
AB  - Evidence from eleven samples indicates that the mean IQ of third world immigrants
      in the Netherlands is lower than the Dutch mean by approximately one standard
      deviation for Surinamese and Antillians, and by approximately one and a half
      standard deviations for Turks and Moroccans. Since IQ tests provide the best
      prediction of success in school and organizations, it could be that the
      immigrants' lower mean IQ is an important factor in their low status on the Dutch
      labour market. The IQs of second-generation immigrants are rising.

PMID- 11446406
TI  - Hirschsprung disease, mental retardation and dysmorphic facial features in five
      unrelated children.
AB  - We report five patients with Hirschsprung disease, severe mental retardation and
      dysmorphic facial features including hypertelorism, prominent forehead and
      dysmorphic ears. All four boys had hypospadias. All had postnatally retarded
      growth. One of them had a de novo apparently balanced translocation
      46,XY,t(2;11)(q22.2;q21). There are several reports on patients with Hirschsprung
      disease, mental retardation and various dysmorphic features. Some of them,
      especially those reported by Tanaka et al. [(1993) Pediatr Neurol 9:479-481],
      Lurie et al. [(1994) Genet Couns 5:11-14] and Mowat et al. [(1998) J Med Genet
      35:617-623] closely resemble our patients suggesting that they have the same
      malformation syndrome.

PMID- 11446407
TI  - Three new European cases of urofacial (Ochoa) syndrome.
AB  - We report on three European cases of urofacial (Ochoa) syndrome. This entity was
      originally described in Colombian patients and very few cases have been reported
      from other countries. It is likely that they may be missed because of variability
      of the urinary problems and failure to recognize the characteristic facial
      grimacing. Establishing an early diagnosis has important consequences for the
      management and prognosis of urinary problems in these patients.

PMID- 11446408
TI  - Digitotalar dysmorphism with craniofacial and other new associated abnormalities.
AB  - We report digitotalar dysmorphism in a grandfather, father, and a daughter. All
      the affected members had clasped thumbs. The father had a short stature, large
      zygomatic arch and a flat mandibular condyle. The newly recognized findings found
      in the affected girl were large maxillary deciduous central incisors, a short
      proximal phalanx of the second finger, and a large subcutaneous hemangioma of the
      back. Her paternal grandfather had only congenital clasped thumbs. Congenital
      clasped thumb is a very heterogeneous anomaly and related to many syndromes. The
      findings in the reported family which are consistent with digitotalar
      dysmorphism, include congenital clasped thumbs, ulnar deviation of fingers, and a
      congenital vertical tali.

PMID- 11446409
TI  - Joint and skin laxity with Dandy-Walker malformation and contractures: a distinct
      recessive syndrome?
AB  - We report the case of a girl who has joint and skin laxity with atrophic
      scarring, and was diagnosed at birth with a Dandy-Walker malformation. She
      subsequently developed joint contractures, hydrocephalus and syringomyelia. This
      case shows some similarities to Ehlers-Danlos syndrome type VI, but with no
      evidence of lysyl hydroxylase deficiency or ocular fragility. It is likely that
      she represents a distinct and recognizable syndrome. There was parental
      consanguinity and a subsequent pregnancy resulted in a similarly affected fetus,
      suggesting autosomal recessive inheritance.

PMID- 11446410
TI  - A novel syndrome with dwarfism, poorly muscled build, absent clavicles,
      humeroradial fusion, slender bones, oligodactyly and micrognathia.
AB  - We report on a 15-year-old girl with severe pre- and post-natal growth
      retardation, poorly muscled build, micrognathia, ulnar ray oligodactyly, absent
      clavicles, abnormal scapulae, humeroradial fusion, hip dislocation, small iliac
      wings, slender tubular bones and normal intelligence. An extensive search has
      failed to ascribe this association to a known condition. This child shared some
      clinical and radiological features with the Yunis-Varon syndrome but the normal
      intelligence and the ulnar ray oligodactyly of our patient does not support this
      diagnosis.

PMID- 11446411
TI  - A case of multiple congenital anomalies in association with Rett syndrome
      confirmed by MECP2 mutation screening.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder. Apparently normal at
      birth, girls with RTT undergo developmental regression and acquire a neurological
      and behavioural phenotype that has been used to define clinical diagnostic
      criteria for the disorder. Recently mutations in the methyl-CpG binding protein 2
      gene (MECP2), located on Xq28 have been identified in females with RTT. We report
      a girl whose clinical course was complicated by congenital abnormalities of the
      respiratory tract and gastrointestinal system. In addition neurological
      abnormalities were evident in the newborn period. By the age of 3 years she had
      developed a phenotype very suggestive of RTT, but had not demonstrated
      deceleration of head growth and the development of expressive language was
      prevented by the presence of the tracheostomy. The clinical impression of RTT was
      confirmed by the recent finding of a mutation in the MECP2 gene. This case report
      highlights the importance of considering the clinical diagnosis of RTT even in
      the presence of other conditions and emphasises that girls with RTT may not be
      normal from birth.

PMID- 11446412
TI  - 3-Hydroxyisobutyric aciduria: phenotypic heterogeneity within a single family.
AB  - 3-Hydroxyisobutyric aciduria is a rare biochemical finding associated with a
      variable clinical phenotype in the literature. We report two siblings excreting
      abnormal levels of this metabolite from a consanguineous family who manifested
      distinct phenotypic variation. We speculate as to whether this biochemical
      anomaly may simply be an incidental finding and suggest that pre-natal
      counselling on the basis of metabolite identification may be unwarranted.

PMID- 11446413
TI  - De novo interstitial long arm deletion of chromosome 3 with facial dysmorphism,
      Dandy-Walker variant malformation and hydrocephalus.
AB  - We report an 8-year-old girl with coarse facial features, macrocrania and
      developmental delay. Cranial anomalies in the form of hydrocephalus and Dandy
      Walker (DW) variant malformation were detected on neuro-imaging. Karyotyping
      revealed a de novo interstitial deletion of bands 3q25.1 to 3q25.33. Deletion of
      the 3q24-q26 region appears to be associated with a somewhat similar
      constellation of findings of craniofacial dysmorphism (broad and depressed nasal
      bridge and low set posteriorly rotated ears), mental retardation, congenital
      heart defects, and central nervous system malformations.

PMID- 11446414
TI  - Campomelic dysplasia without sex reversal in a Turkish patient is due to mutation
      Ala119Val within the SOX9 gene.
AB  - Campomelic dysplasia is a rare neonatal skeletal malformation syndrome mainly
      characterized by congenital bowing and angulation of long bones in combination
      with other skeletal and extraskeletal defects. Two thirds of karyotypic males
      exhibit male-to-female sex reversal. Point mutations within SOX9 in 17q24-25 or
      rearrangements upstream to SOX9 as well as a deletion of a complete gene, causing
      haploinsufficiency of the gene product, have been detected in some patients.
      Recurrent mutations appear to be rare and most mutations detected in campomelic
      dysplasia are family specific. Here, we report on a Turkish patient with a 46,XY
      karyotype affected by campomelic dysplasia without sex reversal. Sequencing the
      SOX9 gene revealed a heterozygous Ala119Val mutation in exon 1, coding for the
      highly conserved HMG-box of the gene. This mutation is not present in the
      parents' lymphocyte DNAs. The same mutation was recently reported in a patient
      with 46,XX karyotype. Additionally, our patient is homozygous for the common
      polymorphism c507C-->T, while both parents are heterozygous.

PMID- 11446415
TI  - Microlissencephaly with cardiac, spinal and urogenital defects.
AB  - We describe two children with a brain defect similar to that described as
      'microlissencephaly', as defined in Barkovich et aL [(1998) Neuroped 29: 113
      119]. Concomitant malformations (cardiac, spinal, urogenital) may represent
      components of a wider syndrome complex; alternatively, or additionally, there may
      have been a valproate teratogenic effect. The inheritance is likely to be
      autosomal recessive, although X-linkage cannot be excluded.

PMID- 11446416
TI  - Popliteal pterygium associated with neonatal Marfan syndrome: case report.
AB  - This report describes the case of a male infant with neonatal Marfan syndrome who
      also exhibited popliteal pterygia. The patient's father had classic Marfan
      syndrome. The differential diagnosis in the neonatal case included congenital
      contractural arachnodactyly (Beals syndrome) and various forms of popliteal
      pterygium syndrome. We note the diagnostic features of the case, discuss the
      novel finding of pterygia in association with neonatal Marfan syndrome, and
      highlight the possible role of collagen defects in the pathogenesis of limb
      pterygia.

PMID- 11446417
TI  - A 46,XX fetus with external female and internal male genitalia, facial dysmorphic
      features and mildly dilated lateral ventricles of the brain: a new syndrome?
AB  - The clinical features of a 46,XX fetus with dysmorphic facial features, mild
      dilatation of the lateral ventricles of the brain, and female external and male
      internal genitalia are described. This combination of abnormalities does not
      appear to have been reported previously, and may represent a new syndrome.

PMID- 11446418
TI  - Hypoplastic left heart and postaxial polydactyly.
AB  - Two siblings are presented with hypoplastic left heart syndrome and symmetrical
      postaxial polydactyly affecting upper and lower limbs. This association has not
      been previously documented. This appears to represent a newly recognized
      syndrome. The inheritance is likely to be autosomal recessive, but other
      inheritance patterns cannot be excluded at present.

PMID- 11446419
TI  - Adams-Oliver syndrome: further evidence for autosomal recessive inheritance.
AB  - We report a 7-year-old girl with Adams-Oliver syndrome who presented with
      extremely rare central nervous system anomalies including microcephaly, epilepsy,
      mental retardation and intracranial calcifications in addition to the classical
      scalp and limb defects.

PMID- 11446420
TI  - Raine syndrome: report of a case with hand and foot anomalies.

PMID- 11446421
TI  - Ophthalmic manifestations of Allgrove syndrome: report of a case.
AB  - A male patient with the ocular manifestations of Allgrove or triple-A syndrome is
      described. The need for early diagnosis based on alacrima, anisocoria and optic
      atrophy of this potentially fatal condition is stressed.

PMID- 11446422
TI  - Maternal-fetal interaction in the ABO system: a comparative analysis of healthy
      mothers and couples with recurrent spontaneous abortion suggests a protective
      effect of B incompatibility.
AB  - We investigated the possible differential effects of A and B blood group materno
      fetal incompatibility on human fertility through a comparative analysis of
      couples with recurrent spontaneous abortion (RSA) and healthy mothers. ABO
      phenotype was determined in 5180 healthy mothers and their newborn babies from
      the population of Sassari (Sardinia) and in 1359 healthy puerperae (women who
      have just given birth) from the population of Rome. Mother-newborn joint ABO
      distribution in healthy mothers was compared with wife-husband joint ABO
      distribution in RSA couples. Distortions from expected distribution were
      evaluated by symmetry analysis. In both RSA couples and healthy mothers
      significant deviation from expected symmetry patterns were observed. Deviations
      in RSA are in the opposite direction to those observed in healthy puerperae. The
      most important difference observed concerned the symmetric joint phenotypes
      mother (women) A/infant (husband) B (B incompatible) and mother (women) B/infant
      (husband) A (A incompatible). A low number of B incompatible in RSA couples and a
      high number of B incompatible in healthy mothers was observed. The phenomenon is
      much more evident in women aged 24-28 years, a period of maximum fecundity. It is
      possible that the presence of anti-B immunoglobulin in the mother might have a
      protective effect against fetal loss in some cases of mother-infant ABO
      incompatibility.

PMID- 11446423
TI  - Genomic diversity at thirteen short tandem repeat loci in a substructured caste
      population, Golla, of southern Andhra Pradesh, India.
AB  - Genomic diversity based on 13 short tandem repeat (STR) loci was studied in seven
      population groups of a substructured Golla caste from Chittoor district in
      southern Andhra Pradesh, India. These groups are traditionally pastoral,
      culturally homogeneous, and strictly endogamous. Blood samples were drawn from
      317 individuals from 30 Golla villages. The 13 STR loci analyzed in five standard
      multiplex polymerase chain reactions were: (1) CSF1R, TH01, and PLA2A; (2) F13A1,
      CYP19, and LPL; (3) D21S1446 and D21S1435; (4) D20S481, D20S473, and D20S604; and
      (5) D5S1453 and D6S1006. The average heterozygosity was found to be low among the
      Golla subgroups (0.64-0.70) in comparison to that of groups at the upper levels
      of the hierarchy. The coefficient of gene differentiation was found to be
      moderate (average GST = 0.031; range between 0.018 and 0.049 among the loci) when
      compared to that observed for a similar class of markers among populations with
      relatively higher levels of hierarchy, for example, among castes. It is, however,
      much higher when compared to the average observed for Indian caste and tribal
      populations, based on classical markers. Genetic distance measures revealed
      clusters of populations that are consistent with the known ethnohistorical and
      geographical backgrounds of the groups. We claim that these hypervariable markers
      are quite useful in understanding the process of substructuring within the Indian
      castes, leading to the formation of smaller breeding isolates, the basic
      Mendelian units within which microevolutionary forces operate.

PMID- 11446424
TI  - Cystic fibrosis mutations and associated haplotypes in Turkish cystic fibrosis
      patients.
AB  - Identification of mutations causing cystic fibrosis (CF) in the Turkish
      population is essential for assessment of the molecular basis of CF in Turkey and
      the development of strategies for prenatal diagnosis and genetic counseling.
      Here, we present an updated report of mutations found in the Turkish CF
      population from an extensive screening study of the entire coding region,
      including exon-intron boundaries and the promoter region. Cases for which
      mutations could not be identified were also screened for previously defined large
      alterations and (TG)mTn-M470V loci. This study revealed a total of 27 different
      mutations accounting for almost 60% of disease genes in the Turkish population.
      In this study, we also identified the haplotypes associated with 17 mutations and
      those associated with unknown mutations. The mutation spectrum of CF in Turkey
      and its associated haplotypes indicated the presence of a major Mediterranean
      component in the contemporary Turkish population.

PMID- 11446425
TI  - Length variations in the COII-tRNA(Lys) intergenic region of mitochondrial DNA in
      Indonesian populations.
AB  - The prevalence of a 9-base-pair (bp) deletion between the mitochondrial
      cytochrome oxidase II (MTCOX*2) and lysine tRNA (MTTK) genes (region V) has been
      used to estimate the genetic relationships among Asian and Pacific populations.
      Many East Asian and Pacific Island populations have been examined previously, but
      the mitochondrial DNA (mtDNA) diversity of the intervening Indonesian archipelago
      has not previously been systematically examined. The 17,500 islands of Indonesia
      currently contain nearly 213 million people and extensive cultural, linguistic,
      and, presumably, genetic diversity. This study of 1091 individuals representing
      15 ethnic groups is the most extensive mtDNA survey to date of the Indonesian
      archipelago. Six distinct length polymorphisms in region V were observed within
      these 15 populations. The 9-bp deletion was found in every population examined at
      frequencies comparable to those of previously examined East Asian populations and
      substantially lower than those in most Pacific Island populations. Despite the
      inclusion of Austronesian-speaking populations and a Papuan-speaking population,
      there was no statistically significant heterogeneity in the frequency of the 9-bp
      deletion among the 15 populations (p = 0.09). These data indicate that
      substantial gene flow occurred among the populations at some time in the past.
      Our observations of no significant correlations between genetic and geographic
      distances (r = -0.04, p = 0.53) coupled with the extensive cultural and
      linguistic differences currently within the archipelago suggest that little gene
      flow among neighboring populations has occurred recently.

PMID- 11446426
TI  - Genetic study of the Paleolithic and Neolithic Southeast Asians.
AB  - DNA samples were extracted from six prehistoric human remains, found on the Malay
      Peninsula, dating to the Paleolithic and the Neolithic periods. Nucleotide
      sequences of mitochondrial DNA were determined by the polymerase chain reaction
      direct sequencing method. A phylogenetic tree between prehistoric and present
      humans was constructed based on the nucleotide sequence data. Mitochondrial DNA
      phylogenetic relationships and ethnoarchaeological evidence suggest that there is
      a continuity beetween the pre-Neolithic humans and the present Semang and that
      the Neolithic humans in this area might be an ancestral group of the Senoi.

PMID- 11446427
TI  - The settlement of Patagonia: a matrix correlation study.
AB  - Matrix correlation represents an innovative methodology to evaluate the
      explanatory power of several hypotheses by measuring their correspondence with
      observed morphological variation. In this paper, we view the origins of
      Patagonians from a matrix correlation approach. Personal and published data on
      nonmetric cranial traits were used to estimate a biological distance matrix
      involving five major groups from Patagonia and two from the northwest and
      northeast regions of Argentina. To evaluate correspondence with other important
      factors, we used a geographic distance matrix and four design matrices,
      representing several patterns of settlement and differentiation. Biological
      distance was found to be strongly associated with spatial separation; the
      correlation between geography and nonmetric cranial distances was highly
      significant. When geographic distance is held constant, correlation between a
      model representing high levels of heterogeneity between the samples and
      morphological (nonmetric) variation becomes highly significant.

PMID- 11446428
TI  - Inbreeding in Gredos mountain range (Spain): contribution of multiple
      consanguinity and intervalley variation.
AB  - The present paper examines consanguineous marriages occurring between 1874 and
      1975 in three valleys (Tormes, Alberche, and Tietar) in the Sierra de Gredos
      mountain range, Avila province, Spain. Information was obtained from parish
      registers of 42 localities, corresponding to a total of 41,696 weddings.
      Consanguineous marriages were defined as those up to the third degree of
      consanguinity (second cousins). From 1874 to 1975 the percentage of related mates
      was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917
      corresponding figures up to the fourth degree were 16.44% and 0.00 19085,
      respectively). In order to ascertain the characteristics and evolution of mating
      patterns in Gredos, the contribution of each degree of kinship was analyzed as a
      whole and then for each valley separately. Regarding total consanguineous
      marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and
      a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of
      consanguinity). Before 1918 multiple matings (i.e., those involving more than a
      single relationship) accounted for 19.16% of consanguineous marriages (up to the
      fourth degree). The observed frequencies of multiple consanguineous marriages
      was, on average, about twice that expected at random, and the proportion of such
      marriages to total inbreeding was 34.65%. The temporal change of the Gredos
      inbreeding pattern was characterized by a recent decrease; the highest inbreeding
      levels correspond to the period from 1915 to 1944. Finally, intervalley
      differences (maximum inbreeding coefficient in the Tormes, minimum in the Tietar)
      are interpreted considering the geography, population size, and population
      mobility for each valley

PMID- 11446429
TI  - International variability of ages at menarche and menopause: patterns and main
      determinants.
AB  - The purpose of this study was to review published studies on the variability of
      age at menarche and age at menopause throughout the world, and to identify the
      main causes for age variation in the timing of these events. We first present a
      summary table including mean (or median) values of the age at menarche in 67
      countries, and of the age at menopause in 26 countries. General linear models
      showed that mean age at menarche was strongly linked to the mean female life
      expectancy, suggesting that one or several variables responsible for inequalities
      in longevity similarly influenced the onset of menarche. A closer examination of
      the data revealed that among several variables reflecting living conditions, the
      factors best explaining the variation in age at menarche were adult illiteracy
      rate and vegetable calorie consumption. Because adult illiteracy rate has some
      correlation with the age at which children are involved in physical activities
      that can be detrimental in terms of energy expenditure, our results suggest that
      age at menarche reflects more a trend in energy balance than merely nutritional
      status. In addition, we found the main determinant of age at menopause to be the
      mean fertility. This study thus suggests that, on a large scale, age at menarche
      is mainly determined by extrinsic factors such as living conditions, while age at
      menopause seems to be mainly influenced by intrinsic factors such as the
      reproductive history of individuals. Finally, these findings suggest that human
      patterns cannot be addressed solely by traditional, small-scale investigations on
      single populations. Rather, complementary research on a larger scale, such as
      this study, may be more appropriate in defining some interesting applications to
      the practical problems of human ecology.

PMID- 11446430
TI  - Population substructure and patterns of quantitative variation among the Gollas
      of southern Andhra Pradesh, India.
AB  - Population substructure and biological differentiation was studied among the
      Golla, a pastoral caste living in the southern areas of Andhra Pradesh (AP) in
      India, using 11 anthropometric measurements and 20 quantitative dermatoglyphic
      variables. The data were collected from a sample of 334 adult males drawn from 30
      villages distributed in the Chittoor district of AP, who belonged to 8 endogamous
      subunits of the same caste. Multiple discriminant analysis of the anthropometrics
      suggests a highly significant degree of discrimination that is consistent with
      the microgeographic variations of the groups. In contrast, in different sets of
      dermatoglyphs discrimination is low and generally inconsistent with both the
      geographic and ethnohistorical affiliations of the groups. These findings are
      reflected in the F(ST) value for anthropometry, which is more than double the
      value of dermatoglyphs. The patterns of gene flow as inferred through the
      regression of phenotypic variance on the distance of groups from the centroid is
      not generally consistent with the known backgrounds in the case of either
      dermatoglyphs or anthropometry. It is concluded that at the level of caste
      substructure representing the lowest level of population hierarchy, the
      quantitative variables examined here may not portray a complete picture of the
      historical process of subdivision. The results of this study are not in
      congruence with those based on another study of 13 short tandem repeat loci on
      the same set of populations (Reddy et al. 2001), which may provide better
      insights into the population structure and history of subdivision that are
      consistent with the known ethnohistorical backgrounds of the populations.

PMID- 11446431
TI  - Duffy antigen/receptor for chemokines (DARC): genotypes in Ashkenazi and non
      Ashkenazi Jews in Israel.
AB  - Duffy genotypes were studied in Ashkenazi and non-Ashkenazi groups in Israel. The
      prevalence of the genotypes for the known polymorphic FY*A, FY*B, and FY*B(GATA-)
      alleles was similar in the two groups. The recently described FY*B(G298A) and
      FY*B(C265T) alleles were also found to be polymorphic. FY*B(G298A) was
      significantly more prevalent in the non-Ashkenazi group than in the Ashkenazi
      group (in 20% and 10% of FY*B, respectively). FY*B(C265T), which markedly
      diminishes the expression of Fy(b) antigen, was found in 3.5% of FY*B alleles,
      but only together with FY*B(G298A), consistent with previous suggestions that
      FY*B(C265T) occurred in the FY*B(G298A) allele. No difference in Duffy genotype
      distribution was found between schizophrenic and control groups. Duffy antigens
      are receptors for chemokines and bind Plasmodium vivax. Study of Duffy genotypes
      in additional populations might help in elucidating the possible functional
      significance of Duffy allele polymorphism.

PMID- 11446432
TI  - Paternal HLA genotype and offspring sex ratio.
AB  - For twenty years, W.H. James has been proposing that the sex hormone level of
      both parents could control at least a quota of the secondary sex ratio variation
      at the time of conception. Observations supporting this hypothesis have come from
      investigations on some diseases related to the human leukocyte antigen (HLA). In
      the present study on 1102 healthy Italian families, we investigated the potential
      effect on the offspring sex ratio of HLA-B alleles on the basis of a genetic
      model. We defined three subsets of HLA-B alleles and hypothesized a locus (L)
      with three alleles, L(H), L(N), L(B15), on the basis of the positive, neutral, or
      negative effect on the testosterone level. According to the genetic model and the
      dominance relation L(H) > L(B15) > L(N), six genotypic and three phenotypic
      classes (H, N, B15) can be expected. We found a significantly high number of
      daughters (66%) born to fathers carrying the B15 phenotype. This result suggests
      an effect of the HLA-B15 allele on the secondary sex ratio, mediated by a low
      testosterone level.

PMID- 11446433
TI  - Dietary zinc supplementation inhibits NFkappaB activation and protects against
      chemically induced diabetes in CD1 mice.
AB  - Zinc status in patients with Type I diabetes is significantly lower than healthy
      controls. Whether zinc supplementation can prevent the onset of Type I diabetes
      is unknown. Recent studies have suggested that the generation of reactive oxygen
      species (ROS) is a cause of beta cell death leading to Type I diabetes. In
      addition, we found that activation of NFkappaB (a ROS-sensitive transcription
      factor that regulates immune responses) may be the key cellular process that
      bridges oxidative stress and the death of beta cells. Zinc is a known antioxidant
      in the immune system. Therefore, this study is designed to test whether an
      increase in dietary zinc can prevent the onset of Type I diabetes by blocking
      NFkappaB activation in the pancreas. The results show that high zinc intake
      significantly reduced the severity of Type I diabetes (based on hyperglycemia,
      insulin level, and islet morphology) in alloxan and streptozotocin-induced
      diabetic models. Zinc supplementation also inhibited NFkappaB activation and
      decreased the expression of inducible NO synthase, a downstream target gene of
      NFkappaB. It is concluded that zinc supplementation can significantly inhibit the
      development of Type I diabetes. The ability of zinc to modulate NFkappaB
      activation in the diabetogenic pathway may be the key mechanism for zinc's
      protective effect. Inhibition of the NFkappaB pathway may prove to be an
      important criterion for choosing nutritional strategies for Type I diabetes
      prevention.

PMID- 11446434
TI  - Metabolism of chylomicron cholesterol is delayed by estrogen. An in vivo study in
      the rat.
AB  - In order to test the effects of estrogen on the clearance of cholesterol of
      dietary origin from the blood and its elimination from the body via the bile in
      an in vivo animal model, the fate of radioactivity from intravenously injected
      [3H]cholesterol-labeled chylomicrons was investigated in the rat. The labeled
      lipoproteins were administered intrajugularly to male rats previously given
      17alpha ethinyl estradiol or the vehicle only, and the removal of the
      radioactivity from the blood and its uptake by the liver and secretion into bile
      was determined. Experiments were carried out in animals with or without prior
      drainage (20 hr) of the pool of bile acids in the enterohepatic circulation, to
      take account of the different demands of the liver for cholesterol in the two
      conditions. In rats without biliary drainage, estrogen treatment decreased the
      rate of removal of radioactivity from the blood by about 30% and the recovery of
      cholesterol in the liver by about 50% in the first 30 min after injection of the
      labeled chylomicrons. After biliary drainage, however, the recovery of label in
      the liver after 90 min was similar in estrogen-treated and control animals,
      although its secretion into bile was markedly reduced in the estrogen-treated
      group (total biliary secretion in 90 min was 26% of the value found in control
      rats). In addition, the apolipoprotein E (aopE) content of the serum total
      lipoproteins was markedly reduced by estrogen. These results provide direct
      evidence indicating that estrogen retards the elimination of dietary cholesterol
      from the body via the bile in the rat, and this is likely to be mainly due to a
      reduced level of apoE in chylomicrons. In view of this, we suggest that the
      hypothesis that estrogen increases the hepatic uptake of chylomicron cholesterol,
      and its excretion in the bile during contraceptive and hormone replacement
      therapy should be re-examined.

PMID- 11446435
TI  - Changes in ryanodine receptor-mediated calcium release during skeletal muscle
      differentiation. II. Resolution of a caffeine-ryanodine paradox.
AB  - Our previous study demonstrated a disparity of action between two established
      pharmacological modulators of the same calcium (Ca2+) release channel, the
      ryanodine receptor (RyR). Specifically, we observed that caffeine sensitivity was
      elicited at earlier stages of development than that of ryanodine. In the present
      study, we offer a hypothesis to resolve this paradox. We provide evidence that
      ryanodine acts as a pure uncompetitive inhibitor of Ca2+ transport, with respect
      to Ca2+ itself. This explains why little ryanodine inhibition was observed at low
      Ca2+ concentrations, while maximal ryanodine inhibition was observed at
      saturating Ca2+ concentrations. In order to exclude the possibility of
      nonspecific ryanodine actions as an alternative explanation, we established the
      phenomenon of capacitative calcium entry (CCE) for L6 cells. Since it is known
      that CCE is inversely correlated with [Ca2+] of the ER/SR lumen, the extent of
      CCE is therefore an indirect measure of Ca2+ concentration within the SR. We also
      demonstrated the functional pathway for Ca2+ entry. Employing pharmacological
      inhibitors, we found that a T-type plasma membrane channel was predominant in the
      myoblasts, while an L-type channel was predominant in the adult myotubes. Our
      data using these inhibitors made nonspecific ryanodine actions an unlikely
      explanation of the disparity in action between ryanodine and caffeine. Moreover,
      we found no evidence that inositol trisphosphate, a proposed regulator of CCE for
      other cells, could influence CCE in L6 cells. We conclude that the disparity
      between caffeine and ryanodine can be explained by Ca2+ dependence of ryanodine
      action. This study may also offer an explanation of other studies showing unclear
      actions of ryanodine binding and action.

PMID- 11446436
TI  - Effects of aging on luteinizing hormone secretion, ovulation, and ovarian tissue
      type plasminogen activator expression.
AB  - This study examined the effects of aging on LH surge magnitude, ovulation, and
      ovarian expression of tissue-type plasminogen activator (tPA), a protease
      implicated in follicular rupture. While mean LH levels and ovulation rates were
      similar in middle-aged cyclic and young groups, there was a significant
      correlation between peak LH levels and ovulation rates in individual rats, such
      that females with lower LH surges ovulated fewer ova. In a separate experiment,
      proestrous LH levels were characterized in young and middle-aged rats, followed
      by in situ hybridization analysis of ovarian tPA mRNA. In young proestrous rats,
      tPA expression was observed in thecal-interstitial cells and oocytes, but not
      granulosa cells, prior to the LH surge. After the LH surge, there was a marked
      increase in tPA mRNA levels in granulosa cells of preovulatory, but not smaller
      follicles, peaking at 0200 hr estrus. By 0500 hr estrus, ovarian tPA expression
      declined, and ovulation had occurred. In contrast, LH-induced follicular tPA mRNA
      levels were dramatically lower in middle-aged rats with attenuated LH surges, and
      persisting preovulatory follicles were common in ovaries of these females on
      estrus morning. These findings suggest that age-related declines in ovulatory
      function result in part from altered induction of ovarian tPA expression, likely
      due to decreased proestrous LH secretion.

PMID- 11446437
TI  - Physical and mechanical characteristics of tibias from transgenic mice expressing
      mutant bovine growth hormone genes.
AB  - Physical and mechanical characteristics of tibia from mice expressing either the
      M4, M11, or G119K mutant bovine growth hormone (bGH) gene and displaying large,
      near-normal, or small-size phenotypes, respectively, were compared to those of
      non-transgenic, control mice (NTC). Three animals of each strain were euthanized
      at 28, 38, 48, 58, and 68 days of age. Variables were regressed against age to
      establish the pattern of change throughout the experiment, and the regression
      results are presented. Tibias from G119K were shorter (13.1 mm) and lighter (37.3
      mg) than those from other strains, and M4 tibias were heavier (87.9 mg) and
      longer (16.6 mm) at 70 days of age. The ratio of tibia length to body weight
      suggests longitudinal bone growth was not reduced as much as overall growth in
      G119K mice. The external and internal dimensions of the G119K tibias were smaller
      than the other strains whereas the M4 tibias were somewhat larger. Differences in
      physical dimensions between the NTC and M11 mice did not greatly affect bone
      mechanical characteristics. Tibias from M4 mice resisted more load at both
      flexure and breaking compared to the other strains. At 50 days of age, stress at
      flexure was greater at all ages for G119K mice (12.4 kg/mm2) and was decreased in
      M4 mice (8.5 kg/mm2). The bGH mutations produce different effects on bone growth
      and its mechanical characteristics. There also may be differential tissue
      responsiveness to the mutant bGH analogs, as longitudinal growth was not as
      affected as empty body growth in the G119K mice. These transgenic mouse strains
      provide valuable models to study bone growth, formation, and reformation in
      response to GH regulation, and more importantly, the M4 and G119K mice may serve
      as a model in which the priorities for GH action on bone vs muscle may be
      determined.

PMID- 11446438
TI  - Effect of estradiol and FBS on PRL cells, GH cells, and PRL/GH cells in primary
      cultures of pituitary cells from prenatal rats.
AB  - The effects of estradiol (E2) treatment on prolactin (PRL) cells, GH cells, and
      PRL/GH cells in immature pituitary cells were determined using primary cultures
      from prenatal rats and immunocytochemistry with fluorescent antibodies. Anterior
      pituitaries obtained from fetuses on day 22 of pregnancy were monodispersed and
      cultured in chemically defined medium or medium containing 10% fetal bovine serum
      (FBS). After pre-incubation for 24 hr, E2 (final concentrations were 0 M, 10(-8)
      M, 10(-7) M, and 10(-6) M) was added into each medium. After 72 hr of incubation,
      cells were subjected to immunocytochemistry. E2 stimulated the increase of PRL
      cells in a dose-dependent manner, and the PRL cell percentage cultured with FBS
      in all groups was significantly higher than that cultured in chemically-defined
      medium. PRL/GH cells also responded to E2 in the same manner as PRL cells. E2 was
      not effective in proliferating GH cells, and GH cell percentage significantly
      decreased with the addition of FBS into the medium. These results suggest that E2
      is dose-dependently capable of increasing immature PRL cells and/or PRL/GH cells
      in vitro. Moreover, there is a factor(s) in FBS that regulates the increase of
      these cells.

PMID- 11446439
TI  - Effect of pre-loading oral glucosamine HCl/chondroitin sulfate/manganese
      ascorbate combination on experimental arthritis in rats.
AB  - The therapeutic effect of a nutritional supplement consisting of a combination of
      glucosamine hydrochloride (FCHG49), purified sodium chondroitin sulfate (TRH122),
      and manganese ascorbate (GCM)3 was investigated in the rat model of collagen
      induced autoimmune arthritis (CIA). The GCM compound was mixed with a palatable
      nutritional paste (Nutri-cal [NC]). Oral administration of the NC/GCM compound
      was initiated in 26 rats 10 days before immunization and continued until the day
      of sacrifice. One group of 12 control rats was given no oral agents; a second
      group of 12 control rats received NC only. Evaluations included arthritis index
      (AI) scoring by three independent evaluators, histologic index (HI) scoring of
      lesions, T-cell proliferation, and serological studies for antibody classes and
      subclasses. Both the AI and HI criteria showed a statistically significant
      reduction in the prevalence of CIA in rats pretreated with the NC/GCM (54%)
      compared to the combined control groups (96%, chi2 analysis P = 0.001). Rats fed
      the NC/GCM also exhibited a significant decrease in the severity of autoimmune
      arthritis in both the AI and HI compared to control Group 2 (immunized-NC) (chi2
      analysis P < 0.05). Histological studies verified the decreased incidence of
      arthritis in the NC/GCM group compared to control Group 2. GCM treatment failed
      to alter T-cell proliferation and antibody production to bovine type-II collagen,
      indicating that its effects are not due to alteration of the antigen-specific
      immune response.

PMID- 11446441
TI  - Comments to the editor concerning the paper entitled "Reproductive malformation
      of the male offspring following maternal exposure to estrogenic chemicals" by C.
      Gupta.

PMID- 11446442
TI  - Physiological role of UCP3 may be export of fatty acids from mitochondria when
      fatty acid oxidation predominates: an hypothesis.
AB  - This hypothesis proposes a physiological role for uncoupling protein-3 (UCP3) in
      the export of fatty acid anions from muscle and brown adipose tissue (BAT)
      mitochondria when fatty acids are the predominant substrate being used. It
      proposes that excess acyl CoA within the mitochondria is hydrolyzed by a
      mitochondrial acyl CoA thioesterase, yielding fatty acid anion and CoASH. The
      fatty acid anion is exported to the cytosol by being carried across the inner
      mitochondrial membrane by UCP3. The CoASH is conserved within the mitochondrion
      to participate in other reactions for which it is needed during fatty acid
      oxidation in the beta-oxidation cycle and in the tricarboxylic acid cycle. The
      export of the fatty acid anion thus permits continued rapid fatty acid oxidation
      in the face of an oversupply. The hypothesis provides a logical explanation for
      the observed up-regulation of gene expression for UCP3 in muscle when there is a
      switch to fatty acid oxidation, as during fasting, and in BAT when fatty acid
      oxidation is stimulated, as during exposure to cold. It provides a plausible
      physiological role for UCP3 as a transporter protein, not as an uncoupling
      protein.

PMID- 11446443
TI  - Hormonal and neurotransmitter roles for angiotensin in the regulation of central
      autonomic function.
AB  - In this review we present the case for both hormonal and neurotransmitter actions
      of angiotensin II (ANG) in the control of neuronal excitability in a simple
      neural pathway involved in central autonomic regulation. We will present both
      single-cell and whole-animal data highlighting hormonal roles for ANG in
      controlling the excitability of subfornical organ (SFO) neurons. More
      controversially we will also present the case for a neurotransmitter role for ANG
      in SFO neurons in controlling the excitability of identified neurons in the
      paraventricular nucleus (PVN) of the hypothalamus. In this review we highlight
      the similarities between the actions of ANG on these two populations of neurons
      in an attempt to emphasize that whether we call such actions "hormonal" or
      "neurotransmitter" is largely semantic. In fact such definitions only refer to
      the method of delivery of the chemical messenger, in this case ANG, to its
      cellular site of action, in this case the AT1 receptor. We also described in this
      review some novel concepts that may underlie synthesis, metabolic processing, and
      co-transmitter actions of ANG in this pathway. We hope that such suggestions may
      lead ultimately to the development of broader guiding principles to enhance our
      understanding of the multiplicity of physiological uses for single chemical
      messengers.

PMID- 11446444
TI  - Biological effects of long-term caloric restriction: adaptation with simultaneous
      administration of caloric stress plus repeated immobilization stress in rats.
AB  - In the present study, we have established the biological effects during 8 weeks
      of (i) caloric restriction (Cal) and (ii) simultaneous administration of Cal plus
      2 hr daily immobilization stress using male Sprague-Dawley rats. Animals were
      divided into three equal groups: (i) ad libitum fed, (ii) 30% restriction of food
      intake of the ad libitum diet, and (iii) 30% restriction of food intake plus 2 hr
      daily immobilization stress. Caloric-restricted animals gained only 30% of the
      total body weight of the unrestricted animals but received 70% of the food of
      those rats. Cal animals showed a significant loss in their relative liver and
      thymus weight and a significant gain in their relative adrenal and testis weight
      as compared to the control animals. Cal animals had almost 2-fold higher levels
      of plasma corticosterone levels with a dramatic decrease in the total
      glucocorticoid receptor (GR) levels in the liver, thymus, heart, and testis as
      compared to ad libitum fed control animals. Interestingly, Cal animals showed
      higher levels of lipid peroxidation in both the liver and heart, indicating
      increased oxidative activities in these tissues when compared with the control
      animals. In addition, Cal animals had increased heat shock protein 70 (HSP 70)
      content in the testis. Surprisingly, hardly any significant differences were
      observed in either total body weight gain, organ weights, plasma corticosterone
      levels, or lipid peroxidation between Cal animals and Cal plus immobilization
      stressed animals. The results obtained suggest that (i) several stress-related
      responses such as inhibition of total body weight gain, increased adrenal weight,
      decreased thymus weight, increased plasma corticosterone, and lipid peroxidation
      levels in the liver and heart are associated with Cal, but (ii) no additional
      effects were observed on the parameters that were measured when two stress
      regimens were given simultaneously, suggesting that animals subjected to two
      stress regimens can protect themselves by controlling their stress-related
      thresholds of response through adaptation.

PMID- 11446445
TI  - Impaired vision and other factors associated with driving cessation in the
      elderly: the Blue Mountains Eye Study.
AB  - The aim of present study was to review vision and other factors associated with
      the cessation of driving. As part of the Blue Mountains Eye Study, detailed
      demographic information, driving status and medical history were taken. Visual
      acuity was measured during a standardized refraction and visual fields
      documented. Potential risk factors were decided a priori. Among the 3654 Eye
      Study participants, 2831 (77.5%) had driven a motor vehicle in the past, of whom
      2379 (84.0%) were current drivers and 452 (16.0%, 95% CI 14.6-17.4%) said they
      had stopped driving. Older persons and women were more likely to have stopped
      driving. After adjusting for age and sex, sensory impairment affecting vision and
      hearing, plus chronic medical conditions and benzodiazepine use were
      significantly associated with cessation of driving. The study found that sensory
      impairment, particularly visual parameters, was associated with the decision to
      stop driving by older subjects.

PMID- 11446446
TI  - Prevalence and associations with ectropion in an older population: the Blue
      Mountains Eye Study.
AB  - The aim of this study was to describe the prevalence of eyelid ectropion and its
      associations with sunlight-related and other ocular variables, plus systemic
      factors, in an older Australian population. The Blue Mountains Eye Study examined
      3654 persons aged 49-97 years. Examination recorded ectropion and other ocular
      signs. The questionnaire assessed sunlight-related and systemic variables.
      Ectropion was present in either eye of 143 subjects (3.9%) and was bilateral in
      101 (70.6%). A marked age-related increase in prevalence was observed with
      ectropion found in 0.3% of persons aged < 60 years, 1.2% of ages 60-69 years,
      6.7% of ages 70-79 years and 16.7% of those aged 80 years or older Ectropion
      prevalence was higher in men (5.1%) than women (3.0%), age-adjusted odds ratio
      2.1 (95% confidence interval 1.5-3.0). Statistically significant associations
      were found between ectropion and history of skin cancer removal, increased skin
      sun sensitivity, lighter iris colour and presence of pingueculum, as well as
      current smoking, hypertension, diabetes and stroke.

PMID- 11446447
TI  - Lower nasal distribution of cortical cataract: the Blue Mountains Eye Study.
AB  - Previous reports have indicated that cortical cataract commences in the lower
      nasal lens, possibly due to sunlight exposure because of the shallow brow
      temporally. The present study aimed to assess the lens sector distribution of
      cortcal cataract in a population. The Blue Mountains Eye Study assessed 3654
      residents aged 49-97 years; 3270 phakic subjects had retroillumination lens
      photographs graded using the Wisconsin method, which divides the lens into eight
      radial sectors with a grid overlay. Graders estimated percentage of cortical
      opacity in each sector. The lower nasal area consistently had the greatest
      opacity, a pattern present at each age and similar in both sexes, despite the 20%
      greater cortical cataract in women. The mean area of lens cortex involved by
      opacities in the lower nasal hemisphere was four fold greater than in the upper
      temporal hemisphere at each age. The lower nasal distributon was highly
      symmetrical when both eyes were affected. When > 20% of the lower nasal lens
      quadrant had cortical opacity, 88% of bilaterally affected subjects had cortical
      cataract n the same quadrant of the fellow eye. The lower nasal distribution may
      indicate a role for sunlight in the aetiology of cortcal cataract, which could be
      considered when examining other cortical cataract risk factors, such as diabetes,
      vascular disease and hormonal factors in women.

PMID- 11446448
TI  - The increasing prevalence of myopia: implications for Australia.
AB  - Myopia is often regarded as a minor priority in public health research, yet the
      public health costs of myopia are considerable, both due to the costs of optical
      correction and from the costs imposed by the morbidity resulting from myopia in
      terms of associated eye disease (glaucoma, posterior subcapsular cataract), and
      the visual impairment and blindness that can result from myopia due to myopic
      retinal degeneration and retinal detachment. There is clear evidence for a high
      and increasing prevalence of myopia in East Asia, apparently driven by increasing
      educational pressures and urbanization. Data from the USA, Europe and Australia
      are consistent with the data from Asia in terms of the role of these risk
      factors. However, the evidence for an increasing prevalence of myopia is more
      problematic, due to the lack of adequate longitudinal studies, and the
      confounding effects of age-related hypermetropization. It is concluded that the
      prevalence of myopia is probably increasing in Australia, although the changes
      are of much lower magnitude than n East Asia. Longitudinal studies are,
      therefore, clearly required to quantify changes in the prevalence of myopia in
      Australia, for accurate assessment of the public health impacts and to assist
      with the development of preventive approaches.

PMID- 11446449
TI  - Changes in attitudes and practices of optometrists in their management of
      diabetic retinopathy after the release of NHMRC guidelines. National Health and
      Medical Research Council.
AB  - The purpose of this study was to document attitudes and practices of Australian
      optometrists in their management of diabetic retinopathy prior to the release of
      the National Health and Medical Research Council (NHMRC) Clinical Practice
      Guidelines for the Management of Diabetic Retinopathy and at two time points
      following their release. A self-administered questionnaire was mailed to a
      stratified random sample of 500 Australian optometrists at the three time points.
      The same sample was used for the first two surveys and a new random sample was
      drawn for the second follow-up survey. The response to the three questionnaires
      was 86%, 80% and 84%, respectively. More than 90% of optometrists reported
      receiving a copy of the guidelines and 82% reported receiving the supplementary
      Retinopathy Chart. Fifty-seven per cent reported having read the guidelines at
      least once in entirety and 65% reported that they refer to the Retinopathy Chart
      at least monthly in their clinical practice. There was a significant decrease in
      the number of optometrists who reported that patient unwillingness to be dilated
      and their fear of precipitating angle closure glaucoma were moderate or major
      barriers to performing dilated ophthalmoscopy. Concomitantly, the percentage of
      optometrists who reported that they often or always perform dilated
      ophthalmoscopy on new patients with diabetes increased significantly from 74.5%
      (95% confidence limit = 70.2, 78.8) to 81.5% (95% confidence limit = 77.5, 85.5).
      There have been some significant changes in the self-reported management
      practices of optometrists in relation to diabetic retinopathy since the release
      of the NHMRC guidelines and Retinopathy Chart.

PMID- 11446450
TI  - Clinical features at presentation of anterior segment pigment dispersion
      syndrome.
AB  - One hundred and twenty patients with anterior segment pigment dispersion syndrome
      were reviewed in order to ascertain the features of the condition and form some
      idea of their significance. Patients were regarded as having pigment dispersion
      syndrome on the basis of heavy trabecular mesh pigmentation with at least one
      other feature of the condition. Although common in men, 44 patients, or a little
      over one-third, were women. Average age at presentation was 47.8 years with women
      presenting 10 years later than men. Intraocular pressure was very variable at
      presentation being less than 20 mmHg in 23 patients. Some patients with elevated
      pressure had no field loss. Variable myopia was recorded in 38 patients: 30
      patients were not myopic. Anterior chamber depth was also variable, the average
      being 3.0 mm, but six patients had a depth of 2.2 mm or less. The syndrome is
      extremely variable in its features at presentation. The mild hypoplasia and the
      hypoperfusion of the iris previously described is consistent with the laxity of
      the iris noted by Ritch and colleagues.

PMID- 11446451
TI  - Intraocular pressure before and after cataract surgery in participants of the
      Melbourne Visual Impairment Project.
AB  - The purpose of this study was to investigate the effect of cataract surgery on
      intraocular pressure (IOP) in a cluster-stratified random sample of the
      population of Victoria, Australia. A total of 3271 participants aged 40 years or
      older were examined at baseline for the Visual Impairment Project. The baseline
      study (1992-1994) was followed by a 5-year incidence study The IOP data were
      compared between participants who had cataract surgery between the two stages of
      the study and participants with and without cataract at follow up. The IOP was
      also compared before and after cataract extraction in glaucoma participants. An
      eligible 89 non-glaucoma and 24 glaucoma participants had cataract surgery
      between the two time points. The analyses showed that IOP increases with age in
      non-operated eyes in both glaucoma and non-glaucoma groups. However IOP decreased
      significantly after cataract surgery in eyes with glaucoma but did not change
      significantly in non-glaucoma participants.

PMID- 11446452
TI  - Differential diagnosis of corneal oedema assisted by in vivo confocal microscopy.
AB  - The purpose of this study was to demonstrate microstructural differences between
      clinically similar, but aetiologically different, cases of corneal oedema in four
      subjects. In vivo confocal microscopy highlighted oedema of the basal epithelium,
      prominent nerve-keratocyte interactions, and typical 'epithelialization' of the
      endothelium in a case of iridocorneal endothelial syndrome; however, a similar
      microstructural appearance was observed in a case of presumed herpetic disciform
      keratitis. The latter diagnosis was subsequently revised on this basis. Confocal
      examination of Fuchs' endothelial dystrophy demonstrated oedema of the basal
      epithelium, prominent wing cells, anterior stromal alterations, fibrosis of
      Descemet's membrane and a typical 'strawberry' appearance of the endothelium. In
      contrast, in vivo microstructural examination of bilateral keratoconus with
      hydrops confirmed oedema mainly involving the epithelium and anterior stroma. In
      vivo confocal microscopy allows the clinician to observe the living cornea at a
      microstructural level and to better diagnose and differentiate borderline or
      unusual cases of corneal oedema.

PMID- 11446453
TI  - Phenotypic analyses of limbal epithelial cell cultures derived from donor
      corneoscleral rims.
AB  - Grafted cultures of limbal epithelial cells aid repair of the corneal epithelium,
      but their phenotype is unclear. In this study, the phenotype of cultures that
      were similar in age to those used clinically were analysed. Limbal epithelial
      cells were isolated from donor corneoscleral rims and grown in various media,
      including those designed for keratinocytes. Successful cultures in each medium
      developed predominantly small (10 microm) tightly packed cells.
      Immunocytochemistry and western blotting revealed expression of keratins 3, 14
      and 19. Expression of these keratins in situ was confirmed by
      immunohistochemistry. Basal limbal epithelial cells were positive for keratins 14
      and 19, and suprabasal cells were positive for keratin 3. However intense
      staining for keratin 14 was also observed at the inner cut edge of corneoscleral
      rims. These findings demonstrate the potential importance of keratins 14 and 19
      as markers of epithelial cell differentiation in the human cornea.

PMID- 11446454
TI  - Adhesion of Pseudomonas aeruginosa ocular isolates to mucin.
AB  - The purpose of this study was to compare the adhesion of Pseudomonas aeruginosa
      ocular isolates to mucin. An adhesion assay was developed using biotin-labelled
      P. aeruginosa strains (two corneal ulcer, two acute red eye, one asymptomatic and
      one standard strains) incubated with porcine gastric mucin immobilized on a
      nitrocellulose membrane. The adhesion was semiquantified using densitometry. The
      results showed that all P. aeruginosa strains tested were able to adhere to mucin
      to various extents with three strains (one corneal ulcer one acute red eye, one
      asymptomatic) binding signifcantly greater than the negative control (P < 0.1).
      Results suggest that ocular strains of P. aeruginosa strains differ in their
      adhesion to mucin but this did not correlate with the pathogenic origin of the
      strain. It is concluded that the adhesion of P. aeruginosa strains to mucin alone
      may not be a principal determinant of pathogenesis but may be a contributing
      factor along with other bacterial virulence traits.

PMID- 11446455
TI  - Serotype and adhesion of Pseudomonas aeruginosa isolated from contact lens
      wearers.
AB  - The purpose of the present study was to correlate the serotypes of Pseudomonas
      aeruginosa to the bacterial adhesion to contact lenses and human corneal
      epithelial cells. Twenty-three strains isolated from contact lens wearers were
      used for the study. The bacterial serotypes were examined with a P. aeruginosa
      antisera kit. The attachment of bacteria on contact lenses or human corneal
      epithelial cells was determined by counting the number of adhered bacteria after
      incubation of the bacteria with contact lenses or corneal epithelial cells. The
      23 ocular isolates belonged to seven serotypes. Strains of serotypes I, G and E
      were the three dominant serogroups and were more adhesive to contact lenses
      compared with other groups of the bacteria. The bacterial serotypes and the
      clinical sequelae were not strongly related. These results indicate that the
      surface characteristics of bacterial serotypes are related to the bacterial
      adhesion to the surface, but the pathogenesis of the bacteria may result from
      multiple factors.

PMID- 11446456
TI  - Production of N-acyl homoserine lactones by gram-negative bacteria isolated from
      contact lens wearers.
AB  - The purpose of this study was to investigate the production of N-acyl-homoserine
      lactone (AHL) signal molecules in ocular gram-negative bacteria. A total of 91
      ocular strains isolated from contact lens adverse response patients and
      asymptomatic subjects were used in the study. These included Acinetobacter,
      Aeromonas hydrophila, Escherichia coli, Haemophilus influenzae, Klebsiella
      oxytoca, Pseudomonas aeruginosa, Serratia liquefaciens, Serratia marcescens, and
      Stenotrophomonas maltophilia. The biosensor strains Chromobacterium violaceum
      mutant CV026 and Agrobacterium tumefaciens A136 were used for detection of AHL
      signal molecules. The majority of A. hydrophila, P. aeruginosa, and S.
      liquefaciens strains produced more than one AHL molecule. Serratia marcescens
      strains were AHL positive only under detection of A136. The rest of the test
      species did not show any AHL production under the current detection system. These
      findings indicate that AHL-mediated quorum-sensing systems are present in some of
      the ocular bacteria, and the different signal molecules may be involved with the
      quorum-sensing pathway in the other bacterial species.

PMID- 11446457
TI  - Random amplified polymorphic DNA analysis of Acinetobacter species isolated from
      worn contact lenses.
AB  - The purpose of this study was to explore the genotypes of Acinetobacter species
      and to compare the genotypes and phenotypes of the Acinetobacter isolated from
      contact lens wearers. Nineteen strains were used in the study, 13 were isolated
      from patients experiencing an adverse response event, and six strains were
      isolated from asymptomatic contact lens wearers. Random amplified polymorphic DNA
      and phenotypic analyses were carried out using commercially available kits.
      Random amplified polymorphic DNA analysis showed a higher discrimination power
      compared with the phenotypic analysis. The test strains were loosely clustered
      into six genotypic groups with no definite relation to any clinical events. These
      results indicate that many genotypes of Acinetobacter can cause adverse
      responses, and the initial source of the microorganisms rather than their
      clinical sequelae may determine classification.

PMID- 11446458
TI  - Antimicrobial peptides: a potential role in ocular therapy.
AB  - Bacterial pathogens are often involved in contact lens-related adverse responses.
      This study aimed to find antimicrobial peptides and proteins that effectively
      eradicate or inhibit ocular bacteria. The antimicrobials were screened against
      gram-negative and gram-positive bacteria originating from ocular sources. The
      viability of these ocular bacteria was measured after exposure to the peptides
      and proteins. Two conditions were used to grow bacteria, low nutrient phosphate
      buffered saline and high nutrient tryptone soya broth. Samples were taken at
      different times up to 48 h. In low nutrient conditions, protamine was found to be
      the most effective against all strains. Melittin was very effectve against all
      strains except Serratia and one Pseudomonas isolate which were partially
      affected. In high nutrient condition, only melittin was effective in killing
      Staphylococcus aureus. Protamine and the combination of protamine and melittin
      had the greatest effect in eradicating the bacteria tested in low nutrient
      condition. Protamine alone and its combination with melittin may have potential
      therapeutic agents for ocular infections in an era of emerging antibiotic
      resistance.

PMID- 11446459
TI  - Lacryglobin in human tears, a potential marker for cancer.
AB  - Lacrygobin has been identified in human tears. This protein has high sequence
      homology to the mammaglobins, proteins upregulated in breast cancer and in breast
      cancer metastasis. In order to investigate the utility of tear screening for
      cancer tear samples were collected from patients with different types of cancer
      and compared to controls. Tear samples were taken from five controls and eight
      breast, six lung, five colon, one prostate and three ovary cancer patients. Tears
      were analysed using 2-D gel electrophoresis (n = 25) and 1-D electrophoresis (n =
      3). Lacryglobin was present in the following percentage of patients: breast
      cancer (88%), lung (83%), colon (100%), ovary (33%), prostate (100%) and controls
      (60%). Two control patients with lacryglobin had a family history of breast and
      prostate cancer. Lacryglobin was detected in some but not all tear samples and
      further studies are warranted to investigate its potential as a marker for
      cancer.

PMID- 11446460
TI  - Pathogenesis and intervention strategies in diabetic retinopathy.
AB  - Diabetic retinopathy is the leading cause of new blindness in the working-age
      population. If improved treatment regimens are to be developed it is crucial that
      the underlying pathophysiological mechanisms responsible for diabetic retinopathy
      are better understood. The multifactorial nature of the many pathways implicated
      in diabetic retinopathy requires a very detailed approach to elucidate the key
      mechanisms involved and their interactions in order to develop logical strategies
      aimed at therapeutic intervention. Fortunately, the streptozotocin rat model of
      diabetes displays many of the morphological and functional changes to the retinal
      vasculature that are evident in human diabetic retinopathy. This study reviews
      some of the recent experimental work by the authors in the streptozotocin rat,
      compares their findings to the human pathology and outlines potential new avenues
      for therapeutic intervention. In particular the improved understanding of which
      layers of the inner retina have the most stringent metabolic demands has helped
      identify which retinal layers are most susceptible to metabolic or
      hypoxic/ischaemic insult. It is concluded that improved treatment outcomes may
      ensue if the therapy is targeted at the appropriate tissue at specific stages of
      the disease.

PMID- 11446461
TI  - A pilot study of in vivo venous pressures in the pig retinal circulation.
AB  - Retinal venous pressure was examined in six pigs using a balanced servo-nulling
      micropuncture technique. The mean transmural venous pressure was 0.95 mmHg (SD
      1.50 mmHg). The transmural venous pressure was lower at the optic disc than away
      from the disc (0.32 +/- 1.46 mmHg vs 1.69 +/- 1.19 mmHg, P < 0.01). At the disc a
      transmural pressure of zero or less (0 to -0.5 mmHg) was demonstrated in 10/21
      (48%) of the disc readings. Over an intraocular pressure range of 15-26 mmHg
      there was a strong correlation between intraocular pressure and retinal venous
      pressure (Pearson coefficient r = 0.92). The results are compatible with the
      Starling resistor theory of venous outflow from the eye.

PMID- 11446462
TI  - Regulatory role of IL-1beta in the expression of IL-6 and IL-8 in human corneal
      epithelial cells during Pseudomonas aeruginosa colonization.
AB  - Pseudomonas aeruginosa is a virulent pathogen and is frequently associated with
      bacterial keratitis. Recent studies have shown that high levels of interleukin
      (IL)-1beta and macrophage inflammatory protein-2 are associated with the severity
      of corneal infection. Interleukin-1beta is a principal inflammatory mediator.
      Understanding the regulatory role of IL-1beta would provide better understanding
      of host responses during P. aeruginosa corneal infection. A human corneal
      epithelial (HCE) cell line and three P. aeruginosa strains were used in this
      experiment. Confluent HCE cells were challenged with P. aeruginosa and monoclonal
      antihuman IL-1beta antibody (IL-1beta mAb). The culture supernatants were
      collected for measuring cytotoxicity and protein levels of IL-1beta, IL-8 and IL
      6 by enzyme-linked immunosorbent assay. Results showed that HCE cells expressed
      low levels of IL-1beta and high levels of IL-6 and IL-8 during P. aeruginosa
      colonization. Paer1-colonized HCE cells produced higher levels of IL-1beta, IL-6
      and IL-8 protein compared to those produced by 6206- and 6294-colonized HCE
      cells. Administration of IL-1beta mAb decreased the production of IL-8 and IL-6.
      In conclusion, P. aeruginosa-colonized HCE cells produced low levels of IL-1beta
      and high levels of IL-6 and IL-8. Neutralizing IL-1beta protein significantly
      downregulated the production of IL-8 and IL-6.

PMID- 11446463
TI  - Effects of a non-steroidal (ketorolac tromethamine) and a steroidal
      (dexamethasone) anti-inflammatory drug on refractive state and ocular growth.
AB  - Topical steroidal anti-inflammatory drugs (SAID) and non-steroidal anti
      inflammatory drugs (NSAID) are known to affect fluid balance. The effects of
      twice daily topical applications of Maxidex (dexamethasone, a SAID), Acular
      (ketorolac, a NSAID), and saline were examined biometrically on the development
      of refractive errors and eye growth in chicks raised from days 3-12 wearing
      either a monocular +10 D, 0 D, or -10 D lens. Biometric analysis showed that
      neither SAID nor NSAID nor saline affected refractive error compensation but that
      the anti-inflammatory drugs affected eye growth. In chicks reared with a +10 D
      lens, dexamethasone induced a decrease in axial length (AL), vitreous chamber
      (VC) and anterior chamber (AC) depth, while ketorolac only induced a decrease in
      AC. In -10 D lens chicks dexamethasone again induced a decrease in AL and VC, but
      did not affect AC depth, whereas ketorolac only induced an increase in AC depth.
      Taken together, these results suggest that anti-inflammatory drugs can induce
      changes in ocular size without affecting refractive state and, as such, have
      implications for the management of progressive myopia.

PMID- 11446464
TI  - Expression of macrophage migration inhibitory factor during Pseudomonas
      keratitis.
AB  - Macrophage migration Inhibitory factor (MIF) is a recently rediscovered pro
      inflammatory cytokine, and has been shown to play a role in the regulation of
      neutrophil chemokines and angiogenesis. Corneal epithelial and endothelial cells
      have been shown to express MIF. This study evaluated the expression of MIF during
      Pseudomonas keratitis in mice and in vitro using a corneal epithelial cell line.
      Three strains of P. aeruginosa, 6294 (invasive strain), 6206 (cytotoxic strain)
      and Paer1 (non-infectious strain) were used. Both cytotoxic and invasive strains
      were isolated from human corneal ulcers and the Paer1 strain was isolated from a
      non-infectious condition. Following challenge in mouse corneas or a corneal
      epithelial cell line, corneal homogenates or lysed corneal epithelial cells were
      used to isolate RNA. Migration inhibitory factor mRNA expression in the mouse
      cornea or human corneal epithelial cells was examined by reverse transcription
      polymerase chain reaction analysis, and was found to be expressed as early as 4 h
      after the injury (scratch controls) or infection in the mouse corneas. Migration
      inhibitory factor mRNA in scratch controls and Paer1-inoculated corneas showed
      peak levels at 4 h post-challenge and this dropped by 24 h post-challenge.
      Corneas challenged with invasive and cytotoxic strains showed peak expression 24
      h post-challenge. Migration inhibitory factor mRNA levels were significantly
      higher in invasive and cytotoxic strain inoculated corneas compared to Paer1
      inoculated corneas. Challenging the corneal epithelial cell line with Pseudomonas
      6294 and 6206 strains induced peak expression at 8 h and levels were decreased by
      12 h. Epithelial cells inoculated with recombinant human interleukin-1beta
      protein induced very high levels of MIF mRNA at all time points compared to
      infected and control corneal epithelial cells. High expression of MIF in the
      infected corneas suggests that it may have a role in the pathogenesis of corneal
      disease induced by invasive and cytotoxic strains of P. aeruginosa.

PMID- 11446465
TI  - Localization of voltage-sensitive L-type calcium channels in the chicken retina.
AB  - L-type calcium channels have been associated with synaptic transmission in the
      retina, and are a potential site for modulation of the release of
      neurotransmitters. The present study documents the immunohistochemical
      localization of neuronal alpha1 subunits of L-type calcium channels in chicken
      retina, using antibodies to the alpha1c, alpha1d and alpha1f subunits of L-type
      calcium channels. The alpha1c-like subunits were localized to Muller cells, with
      predominantly radial processes, and a prominent band of horizontal processes in
      the outer plexiform layer. The antibody to alpha1d subunits labelled most, if not
      all, cell bodies. The antibody to a human alpha1f subunit strongly labelled
      photoreceptor terminals. Fainter immunoreactivity was detected in the inner
      segments of the photoreceptors, a subset of amacrine cells, two bands of
      labelling in the inner plexiform layer and many ganglion cells. The differential
      cellular distributons of these alpha1-subunits suggests subtle functional
      differences in their roles at different cellular locations.

PMID- 11446466
TI  - Effects of triamcinolone acetonide on microglial morphology and quantitative
      expression of MHC-II in exudative age-related macular degeneration.
AB  - Animal models, in vitro assays and pilot clinical studies suggest that
      intravitreal triamcinolone acetonide may be useful in the treatment of age
      related macular degeneration. The present case study reports the effect of
      intravitreal triamcinolone acetonide injection on a subretinal neovascular
      lesion, microglial morphology and quantitative expression of MHC-II antigens.
      Triamcinolone acetonide significantly decreased MHC-II expression consistent with
      immunocytochemical observations which revealed condensed microglial morphology.
      The modulation of subretinal oedema and microglial morphology correlates with in
      vitro observations suggesting that downregulation of inflammatory markers and
      endothelial cell permeability are significant features of the mode of action of
      triamcinolone acetonide.

PMID- 11446467
TI  - The contribution of cone responses to rat electroretinograms.
AB  - The contribution of rods and cones to the scotopic electroretinogram (ERG) of
      small animals is unclear, with a recent report suggesting that the mouse has no
      cone a-wave. The present study considered the contribution of cones to the ERG of
      the rat. Dark-adapted Long Evans rats (n = 4) had ERG signals collected following
      a single flash, which stimulated rods and cones (mixed response), or a twin-fash
      paradigm (short interstimulus interval, 1 s), which isolated cone responses. Rod
      signals were derived by digital subtraction of the cone signal from the mixed
      rod/cone ERG. The rat a-wave was found to be dominated by rod responses but cone
      responses contributed substantially (45%) to post-receptoral waveforms (b-wave)
      at higher light levels.

PMID- 11446468
TI  - Achromatic impulses unmask L- and M-cone adaptive mechanisms.
AB  - The mechanisms underlying the adaptive response for achromatic impulses seen on
      achromatic fields were investigated. Foveal thresholds were measured for a static
      probe-impulse under two conditions of adaptation. Thresholds were obtained under
      gain-clamped conditions after observers had reached steady-state adaptation and
      with a probe-flash paradigm. It was found that thresholds isolated on steady
      state fields cannot be modelled using a single mechanism. Likewise, the probe
      flash condition failed to reflect the response of a single mechanism. Both
      threshold functions showed distinct breaks occurring at about the same field
      luminance (approximately 1.0 log cd/m2). Optimum data fits required the
      incorporation of two mechanisms implying the existence of independent processes
      mediating detection. Chromatic isolation confirmed that differential adaptation
      had been unmasked in the long- and medium-wavelength sensitive cone inputs to the
      achromatic channel.

PMID- 11446469
TI  - Pretectal neurons responding to slow wide-field retinal motion: could they
      compensate for slow drift during fixation?
AB  - The visual response properties are described of a group of retinal slip neurons
      in the wallaby pretectum, referred to as slow cells. Their responses to motion
      are direction-selective: tempero-nasal and naso-temporal motion over the
      contralateral eye increase and decrease, respectively, the firing rate relative
      to the spontaneous level. Slow cells are maximally sensitive to image velocities
      from 0.08 to 10 degrees/s. The present study focuses on slow cells that are
      maximally sensitive to image velocities below 1 degree/s. An interesting
      characteristic of 82% of slow cells is that once motion stops, the firing rate
      exhibits a same-sign after-response. This is characterized by a slow exponential
      return from the firing rate during motion to the spontaneous rate. The time
      constants of the after-responses are independent of the temporal frequency
      velocity, duration and direction of the motion stimulus. It is proposed that the
      neurons may assist the stabilization of eye position during fixation.

PMID- 11446470
TI  - An isolated abdominal wall metastasis of ovarian carcinoma ten years after
      primary surgery.
AB  - This report describes the case of a woman with early stage ovarian carcinoma who
      developed an isolated metastasis in the anterior abdominal wall following an
      apparent disease-free interval of ten years. The management of the case is
      discussed and important factors are highlighted. Comparison is also made to the
      phenomenon of port-site recurrence following laparoscopy in cases of ovarian
      carcinoma.

PMID- 11446471
TI  - Lymphoid elements and apoptosis-related proteins (Fas, Fas ligand, p53 and bcl-2)
      in lichen sclerosus and carcinoma of the vulva.
AB  - We studied some of the morphological and immunohistochemical parameters of lichen
      sclerosus (LS) and carcinomas of the vulva in order to verify some
      characteristics in LS related to neoplasm transformation. Parameters such as
      proliferating index, rate of proliferation of lymphoid elements into a tumor and
      types of such elements were studied. In parallel, the number of cells positive to
      apoptosis-related proteins such as Fas, Fas ligand, p53 and bcl-2 were evaluated.
      Biopsy material from patients with different vulvar disorders--22 samples with LS
      and 23 samples with vulvar squamous cell carcinoma (VSCC)--was studied by the
      methods of morphometry and immunohistochemistry. In LS, the number of T cells is
      a few times higher than those of B cells. Among the T cells, the number of
      killers is significantly higher than the number of helpers. Carcinomas,
      especially those with lymphoid depletion, are characterized by a further
      significant increase in some parameters such as the rate of lymphoid
      proliferation and the number of T helpers and killers. The progression in to
      tumorigenesis was accompanied with a significant increase in the number of Fas+
      and FasL+ lymphocytes. In tumor epithelial cells the proliferative index
      increased in carcinomas with lymphoid depletion. The number of p53+ epithelial
      cells increased whereas the number of bcl-2+ cells showed a distinct tendency to
      decrease with progression in to tumorigenesis. Development of a tumor is
      manifested in deep changes in relationships between different lymphoid
      components. Only two lymphoid markers are significantly different in VSCC
      compared to LS: the number of T killers and macrophages. The other parameters
      studied (rate of proliferative activity, the total number of T cells and T
      helpers, B cells, IL-2-connective cells) already showed high expression in LS as
      the first signs of transformation of this inflammation into neoplasia.

PMID- 11446472
TI  - On the site of origin of epithelial tumors of the ovary.
AB  - Ovaries removed at 1,050 autopsies (accidental deaths) and from 300 patients with
      various benign gynaecological diseases were studied in search of the incipient
      benign epithelial tumors. One percent of the ovaries contained incipient mucinous
      tumors, 1.1%--Brenner tumors, 0.5%--endometrioid tumors. The exact percentage of
      the serous tumors was difficult to establish because of the absence of
      morphological criteria that distinguish these tumors from tumor-like conditions
      (inclusion cysts). The mucinous and Brenner tumors, as well as some serous tumors
      were located deep in the medullary or hilar regions of the ovary and were not
      connected to the covering of the ovary. The theory of incessant ovulation that
      links ovulatory damage of the ovarian surface with the initiation of neoplastic
      growth does not explain the genesis of all epithelial tumors. It is more likely
      that the latter two types arise in other parts of the female gonad. The process
      of morphogenesis of epithelial benign tumors is closely related to stromal
      alterations, specific for each histogenetic entity.

PMID- 11446473
TI  - Pleomorphic rhabdomyosarcoma of the uterine corpus: a case report.

PMID- 11446474
TI  - Laparoscopically-assisted intraoperative lymphatic mapping in endometrial cancer:
      preliminary results.
AB  - OBJECTIVE: To analyse the results of a pilot study and determine the contribution
      of laparoscopically-assisted lymphatic mapping in patients with endometrial
      cancer. METHODS AND MATERIALS: In eight cases of early endometrial cancer, patent
      blue-V was injected laparoscopically into the uterine wall during a surgical
      staging procedure. RESULTS: A deposition of the blue dye was found in at least
      one pelvic lymph node in five of eight cases. Blue-colored nodes were observed in
      a total of 11 lymph nodes. Locations of these nodes included obturator, internal
      and common iliac sites. Only one blue colored node was positive for disease. An
      average of 15 lymph nodes were removed in the study group (range, 12-22). Uterine
      lymphatic vessels with bilateral drainage to the broad and infundibulopelvic
      ligaments were seen in all cases within 30-60 seconds. CONCLUSION: Our initial
      experience with laparoscopically-assisted lymphatic mapping confirmed that the
      use of a minimally invasive technique is feasible. Lymphatic channels in the
      pelvic areas were seen in every patient. A deposition of blue dye in
      laparoscopically identifiable lymph nodes was seen only in 62.5% of patients.
      However, we believe that the lymphatic mapping of the uterine corpus can improve
      the accuracy of surgical staging in patients with endometrial cancer.

PMID- 11446475
TI  - Comparative immunohistochemical study of endometrioid and serous papillary
      carcinoma of endometrium.
AB  - OBJECTIVE: The aim of this study was to determine whether immunohistochemical
      analysis of molecular parameters can provide an alternative method for
      classification of endometrial cancer cases according to their aggressiveness.
      METHODS: Sixty-four cases of endometrial carcinoma were assigned to three groups:
      group I--28 cases of endometrioid well and moderately differentiated (G1-G2)
      carcinoma; group II--14 cases of endometrioid poorly differentiated (G3)
      carcinoma; group III--22 cases of serous papillary endometrial cancer.
      Immunohistochemistry was used to determine the existence of estrogen receptors
      (ER), progesterone receptors (PR), and the expression of bcl-2, p53, HER-2/neu
      and Ki-67. RESULTS: There was a significant difference in the immunohistochemical
      profile of the studied molecular parameters comparing the three study groups. The
      endometrioid G1-G2 cases (group I) were characterized by increased
      immunoreactivity for ER and PR (85.7% and 78.6%, respectively), increased
      immunoreactivity for bcl-2 (42.8%) and low expression of p53 (14.3%) and HER
      2/neu (14.3%). In contrast to group I cases, the serous papillary endometrial
      cancer cases (group III) were characterized by immunonegativity for ER, PR and
      bcl-2 and high immunoreactivity for p53 (81.8%) and HER-2/neu (45.4%). The
      endometrioid G3 cases (group II) demonstrated an intermediate immunoprofile,
      characterized by immunonegativity for ER, PR and HER-2/neu, low immunoreactivity
      for bcl-2 (7.1%) and high expression of p53 (57.1%). The expression of Ki-67 did
      not differ significantly comparing the different cases of endometrial cancer.
      CONCLUSION: This study provides evidence that the immunohistochemical analysis of
      endometrial carcinoma differentiates between different grades and histological
      types, thus being useful in the distinction of high risk cases.

PMID- 11446476
TI  - Comparison of enoxaparin and standard heparin in gynaecologic oncologic surgery:
      a randomised prospective double-blind clinical study.
AB  - OBJECTIVE: This study aimed to compare the haemorrhagic complications and
      efficacy of enoxaparin, a low molecular weight heparin (LMWH), and conventional
      standard heparin (SH) in gynaecological oncologic surgery. MATERIALS METHODS: A
      double blind, randomised trial was performed on 102 consecutive women undergoing
      gynaecologic cancer surgery with pelvic and paraaortic lymphadenectomy. The women
      were separated into those who were given 2,500 IU enoxaparin once daily and SH in
      a dose of 5,000 IU three times daily. The groups were analysed for intraoperative
      blood loss, drainage, transfusion requirements, perioperative haemoglobin
      decrease, wound haematoma, and clinical deep venous thrombosis. RESULTS: The two
      groups were well matched for age, weight, and other factors, which could
      predispose to the development of deep venous thrombosis (DVT) and haemorrhage. No
      patient developed clinical significant DVT, wound haematoma or intra-abdominal
      bleeding. There was no significant difference in bleeding complications between
      the two regimens. The antiFXa level in the plasma was correlated strongly with
      patient weight. CONCLUSIONS: A dose of 2,500 IU enoxaparin/day does not cause
      more bleeding complications than SH 5,000 IU three times daily when used to
      prevent thrombosis. However, the dose of enoxaparin must be adjusted to the
      patient's weight.

PMID- 11446477
TI  - Appraisal of imprint cytology in the diagnosis of mucinous carcinoma of the
      breast: a case report.
AB  - A case of mucinous carcinoma of the breast is reported in a female aged 71 years.
      On gross examination of the left mastectomy specimen two relatively well
      circumscribed masses with a gelatinous cut surface were found. Touch imprint
      cytology was consistent with a low-grade malignancy and histologic and
      histochemical examination revealed a mucinous carcinoma. Careful prospective
      correlation between the cytological appearances of cells in imprints and the
      subsequent histopathology may lead to a more precise cytodiagnosis of a tumor
      associated with a comparative good prognosis.

PMID- 11446478
TI  - Detection of Chlamydia trachomatis infection in women with CIN and invasive
      carcinoma. Controversial results of different methods.
AB  - Chlamydia (Ch.) trachomatis infection as a sexually transmitted disease is highly
      important, but reliable methods of diagnosing it remain to be worked out. We used
      three methods of detection: an immunoenzymatic technique for detection of Ch.
      trachomatis antigen in endocervical material, in situ PCR, and enzyme-immuno
      assay for detection of IgG class anti-Ch. trachomatis antibodies in serum. We
      have compared the IS-PCR technique and method of detection of the endocervical
      antigen. We have not confirmed compatibility of the results obtained in these two
      methods. Parallel positive results obtained in patient serum and detection of
      chlamydial DNA by IS-PCR have been accepted to be indicative of persistent
      infection of Ch. Trachomatis.

PMID- 11446479
TI  - Preoperative discrimination between malignant and benign adnexal masses with
      transvaginal ultrasonography and colour blood flow imaging.
AB  - BACKGROUND: Ovarian cancer is one of the causes of death in women, and in about
      70% of cases is recognized only in advanced stages. This study was undertaken to
      evaluate distinctive values of transvaginal and color Doppler ultrasonography in
      differentiating malignant and benign adnexal masses through analysis of
      ultrasonic morphological features of malignancy and estimation of location and
      intensification of angiogenesis as well as values of resistance of flow in
      examined masses. PATIENTS AND METHODS: 329 women with malignant and benign
      adnexal masses underwent ultrasonographic and colour Doppler examination 1-5 days
      before surgery (laparotomy, laparoscopy) thus allowing histological verification
      of diagnosis. The ultrasonographic structure was assessed using a morphological
      scoring system devised by Sassone, Jain and Benacerraf. Regions showing
      vasculature, especially within septae and solid parts of tumours were examined by
      means of transvaginal colour Doppler. Location and intensification of
      angiogenesis as well as resistance index (RI) were investigated. Sensitivity,
      specificity, PPV and NPV of both techniques were assessed. Statistical analysis
      of obtained data were based on the Student's t test; p < 0.05 level was
      considered significant. RESULTS: Postoperatively 255 (77.5%) benign and 74
      (22.5%) malignant tumours were seen. In the group of benign masses the average
      age of women was 42.6+/-12.3 and in the malignant it was 53.1+/-12.6 (p<0.0001).
      The transverse dimension of benign lesions was 77.2+/-19, whereas for malignant
      it was 107.0+/-31 (p<0.0001). Benign tumours in 63.0% were cystic, in 26.0% mixed
      cystic-solid and in 11.0% solid echostructures while in malignant they were
      respectively, 6.8%, 56.8% and 36.4% (p<0.0001). Doppler flow within the tumour
      was 74.5% in benign and 98.6% in malignant masses (p<0.0001). In benign lesions
      homogenous superficial or peripheral vasculature was visualized, and in the
      majority of cases (82.7%) it was of medium intensification. However in malignant
      central, peripheral or mixed vascularisation. in the majority intensified
      character was found. Average value of the resistance index in all benign masses
      amounted to 0.77+/-0.14, however in malignant it was 0.39+/-0.07 (p<0.0001).
      CONCLUSIONS: We contend that complete ultrasonographic estimation of ovarian
      neoplasms outside the qualification of structural details should include Doppler
      analysis of vasculature parameters. Most important is the qualification of
      resistance of flow, and location and intensification of vascularisation in
      examined masses which permit the differentiation of malignant and benign lesions.
      Preoperatively recognizing malignant processes with colour Doppler
      ultrasonography shows higher accuracy, specificity and PPV.

PMID- 11446480
TI  - Primary squamous cell carcinoma of the endometrium. A report of 3 cases.
AB  - Primary squamous cell carcinoma of the endometrium (PSCCE) is a rare disease of
      unknown etiology. Diagnosis is based on the identification of squamous cell
      carcinoma in the endometrium with no coexisting analogous cervical component or
      endometrial adenocarcinoma. There must also be no connection between the
      endometrial tumour and the squamous epithelium of the cervix. Although the
      majority of patients are classified as stage I disease, prognosis is rather
      dismal. We report two new cases of primary squamous cell carcinoma of the
      endometrium which fulfill all the above criteria and we discuss another
      interesting case of squamous cell carcinoma of questionable endometrial origin.
      Management by abdominal hysterectomy and adjuvant pelvic irradiation resulted in
      long-term survival of our patients.

PMID- 11446481
TI  - Ductal breast carcinoma metastatic to the vulva: a case report.

PMID- 11446482
TI  - Primary diffuse large B-cell lymphoma of the breast: a case report.
AB  - Mammary non-Hodgkin's lymphomas are uncommon and account for 2% of all extranodal
      lymphomas. Stringent diagnostic criteria are applied in the diagnosis of primary
      lymphoma considering that the breast is a recognized site for disseminated
      extranodal lymphoma. Our case report was established by histology alone.

PMID- 11446483
TI  - Adenocarcinoma, adenoacanthoma, and mixed adenosquamous carcinoma of the
      endometrium.
AB  - PURPOSE: To determine the frequency of endometrial adenocarcinoma (AC) with
      squamous cell differentiation and to compare the histopathologic and clinical
      characteristics of patients with adenoacanthoma (AA) and adenosquamous carcinoma
      (AS) to evaluate possible prognostic differences. MATERIALS AND METHODS: Two
      hundred forty patients with endometrial carcinoma (72.2% AC, 21.25% AA, 6.25% AS)
      treated at the Department of Gynecologic Oncology of Marmara University Hospital,
      between January 1986 and December 1997, were reviewed. The diagnoses of the
      diseases were made with fractional D&C, and the definitive therapy for all
      patients was carried out at the same hospital. Extrafascial hysterectomy + BSO
      with or without pelvic and para-aortic lymph node dissection, and omentectomy
      according to the FIGO staging and grading system were performed. RESULTS: AC and
      AS had median ages around 60 years with a similar percent distribution of
      postmenopausal patients (around 74%). AA had an earlier median age of 51 years
      which reflects an incidence of only 50% postmenopausal patients. There was a
      tendency for AA to be of low-grade malignancy (72%), 51% of AC were of low-grade,
      while only 20% of AS were low-grade tumors. There was no difference for any of
      the three pathological entities in survival by FIGO stages. Over 80% of the
      tumors were Stage I and about 10% were Stage II, with less than 10% in Stages III
      and IV. CONCLUSION: Considering the more modern and uniform approaches in therapy
      for these tumors, there seems to be no differences in prognosis for
      adenocarcinoma with or without squamous elements. The neoplasms AC, AA and AS
      should be regarded, and consequently approached, as any low-grade adenocarcinoma
      of the endometrium.

PMID- 11446484
TI  - Central nervous system involvement in gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To evaluate characteristics of patients with central nervous system
      (CNS) lesions of gestational trophoblastic disease and determine prognostic and
      therapeutic implications applicable to management. METHODS: Nine patients among
      56 cases of malignant gestational trophoblastic neoplasia (GTN) were analyzed
      prospectively in a single institution between the years 1990 and 1997 with at
      least two years of follow-up. Brain metastases were documented by physical exam
      and computed tomography scan or magnetic resonance imaging. In terms of therapy,
      all of the patients received an etoposide, methotraxate, actinomycin,
      cyclosphamide and vincristine (EMA-CO) regimen for 5 to 9 courses. To prevent
      unexpected intracranial hemorrhage, all patients received radiation therapy. No
      intrathecal chemotherapy was given. Remission was defined as three weekly beta
      hCG levels below assay sensitivity (<5 mIU/ml). RESULTS: The mean age of the
      patients at diagnosis was 29.6 years. While two of the patients initially
      presented with symptoms related to cranial involvement, five were diagnosed
      during routine investigation for metastasis in malignant GTD and the remaining
      two developed cerebral metastases during the therapy. Besides central nervous
      system involvement, six had additional lung, two had hepatic and splenic and one
      had pelvic metastases. Overall survival was 66.6%. Two patients had a fulminant
      clinical course and were lost one month after initial diagnosis. CONCLUSION:
      Early diagnosis via computed tomography of the head and beta-hCG serum testing
      along with aggressive, multiagent intervention (EMA-CO) have greatly improved
      patient prognosis of this once highly fatal condition.

PMID- 11446485
TI  - Breast cancer in ectopic breast tissue.
AB  - Ectopic breasts usually develop along the mammary ridges. Their incidence has
      been reported as up to 5-6%. Development of malignancy is rare. We report three
      cases of postmenopausal female patients with breast cancer which developed in the
      axillary accessory breast. They were all successfully treated by surgery and
      adjuvant therapy. A review of the literature on the incidence and pathology of
      ectopic mammary tissue is also presented.

PMID- 11446486
TI  - Prognosis and treatment of primary adenocarcinoma and adenosquamous cell
      carcinoma of the uterine cervix.
AB  - PURPOSE: To evaluate a cohort of women with primary invasive carcinomas of the
      uterine cervix, and to compare the biological characteristics and behavior of a
      cohort of adenosquamous carcinomas with a cohort of adenocarcinomas and squamous
      cell carcinomas. METHODS: One hundred and fourteen cases of primary invasive
      cervical carcinoma presenting between 1 January 1987 and 31 December 1997 were
      studied. Sixteen (14%) women with adenosquamous cell carcinomas and eight (7%)
      adenocarcinomas were compared with 90 (79%) women with squamous cell carcinomas.
      Patients with Stage Ib and IIa were treated by radical hysterectomy and pelvic
      lymph node dissection. All patients with stage IIb and over were treated by
      radiation. Patients with bulky, large, barrel-shaped lesions were selected for
      treatment by a combination of radiation and extrapelvic hysterectomy. RESULTS:
      The corrected survival rate for stage Ib patients with adenosquamous cell
      carcinoma was only 27.2%, compared with a 92.2% corrected survival rate for
      squamous cell, and a 100% corrected survival rate for adenocarcinoma. CONCLUSION:
      There is a higher proportion of adenosquamous cell and adenocarcinoma of the
      cervix than generally appreciated. The epidemiological risk factors associated
      with adenosquamous carcinomas of the cervix are more similar to those of squamous
      cell carcinomas than of adenocarcinomas. The survival difference between two
      groups is explained by effects of clinical stage, nodal spread, and vascular
      space involvement.

PMID- 11446487
TI  - Surgery in ovarian cancer.
AB  - The role of surgery in the management of primary and recurrent ovarian cancer is
      reviewed. The data to support primary and secondary cytoreduction are summarized.
      The role of second-look surgery and of surgery in the palliation of ovarian
      cancer is also discussed.

PMID- 11446488
TI  - Recent data about endometrial carcinoma: potential of anti-aromatase agents.

PMID- 11446489
TI  - ESGO consensus document on cervical cancer screening. European Society of
      Gynaecological Oncology.

PMID- 11446490
TI  - Effects of hot bath immersion on autonomic activity and hemodynamics: comparison
      of the elderly patient and the healthy young.
AB  - Hot bathing has been associated with sudden death and so the present study
      investigated its effects on autonomic activity and hemodynamics in the elderly
      patient and the healthy young by analyzing heart rate variability (HRV). Subjects
      were 9 elderly men (mean age, 75 years) and 9 young men (mean age, 27 years), who
      were immersed up to shoulder level while in a sitting position for 10min with the
      bath temperature at 40 degrees C. Blood pressure (BP) and heart rate (HR) were
      monitored. BP in the young decreased during bathing (p<0.01), whereas in the
      elderly BP had a maximum value just at the start of immersion (p<0.05) with a
      slight decline at 4 min after the start of immersion. Although HR in the young
      increased (p<0.01), in the elderly there was an abrupt increase in HR just at the
      start of immersion (p<0.05), followed by a decrease in HR. With regard to HRV,
      the high-frequency (HF) component in the young men was suppressed during
      immersion (p<0.01), but was unaffected in the elderly. The LF (low frequency)/HF
      ratio in the elderly decreased at 4 min (p<0.05). In conclusion, hypotensive
      syncope may cause sudden death by drowning during hot bathing, and is a
      consequence of the decrease in sympathetic tone that develops approximately 4min
      after immersion.

PMID- 11446491
TI  - Circadian variation of autonomic nervous activity in patients with multivessel
      coronary spasm.
AB  - The present study investigated whether the circadian rhythm of sympathovagal
      activity is related to the severity of coronary spasm or multivessel coronary
      spasm. Heart rate variability was examined in 22 consecutive patients with
      vasospastic angina provoked by intracoronary injection of acetylcholine, who had
      either multivessel spasm (Group M, n=11 ) or single vessel spasm (Group S, n=
      11), in 20 subjects without coronary artery disease (Group C) and 20 patients
      with effort angina who had organic coronary artery stenosis (Group E). The
      frequency domain indices were analyzed, including low frequency (LF: 0.04-0.15
      Hz) and high frequency (HF: 0.15-0.4Hz), the latter being an index of efferent
      parasympathetic activity, and the ratio (L/H) as an index of sympathovagal
      balance. The circadian variation of the parameters was analyzed by its pattern
      and was quantified by the difference of the mean values between daytime and
      nighttime. Although the HF power increased during nighttime in Groups C and S,
      this increase was attenuated in Groups E and M. The circadian variation of the
      L/H ratio (ie, a drop during nighttime) was smaller in the S and M groups than in
      Groups C and E. Accordingly, in Group M, the circadian variation of both
      sympathetic and parasympathetic nervous activity was attenuated, but in Group S,
      the variation of sympathetic nervous activity, but not parasympathetic nervous
      activity, was decreased. These data suggest that relatively enhanced sympathetic
      nervous activity at night may be involved in the mechanism underlying multivessel
      coronary spasm.

PMID- 11446492
TI  - Balloon aortic valvuloplasty in children: a multicenter study in Japan.
AB  - A questionnaire was used to survey the experience of 8 Japanese institutions with
      percutaneous transluminal aortic valvuloplasty (PTAV) in children. Among 99
      procedures reported in 88 patients, sufficient data for analysis was obtained
      from 76 procedures in 72 patients. In those 76 procedures the pressure gradient
      decreased significantly from 68+/-25 (20-140) to 33+/-22 (0-100) mmHg (p<0.01),
      whereas aortic regurgitation (AR) increased at least one grade in 26 cases (34%).
      None of the parameters analyzed in this study were predictors of an increase in
      AR. The reduction in pressure gradient was judged as good in 44 of the 76
      procedures (58%). A larger ring diameter, larger balloon diameter and larger
      ratio balloon diameter/the normal predicted diameter of the aortic valve ring
      significantly contributed to an effective reduction of pressure gradient. Follow
      up data (mean interval, 4 years) was available for 26 of 39 clinically effective
      procedures. AR progressed at least 1 grade in 11 (42%), and the pressure gradient
      re-developed to more than 50mmHg in 2 cases (8%). In Japan, PTAV has been
      accepted as a useful procedure for valvular aortic stenosis in children, but
      progressive AR or re-development of the pressure gradient is not uncommon even
      after clinically effective PTAV.

PMID- 11446493
TI  - The D allele of the angiotensin-converting enzyme gene and reperfusion-induced
      ventricular arrhythmias in patients with acute myocardial infarction.
AB  - The renin-angiotensin system may play a pivotal role in reperfusion ventricular
      arrhythmias (RVA). The purpose of this study was to investigate the association
      between angiotensin-converting enzyme (ACE) gene polymorphism and RVA in patients
      with acute myocardial infarction (AMI) in a case-control study. Patients who had
      undergone successful coronary intervention for AMI were enrolled (n= 127,
      male/female: 97/30, mean age, 62.6 years). The incidence of RVA was continuously
      monitored by ECG at a coronary care unit. The severity of ventricular arrhythmias
      was evaluated in terms of the Lown's grade and patients with a high risk of
      ventricular arrhythmias that may cause sudden cardiac death (Lown's grade > or
      =2) within 5 h of coronary intervention were defined as cases (n=59), and
      otherwise as controls (n=68). A receiver operating characteristic curve was used
      to determine the discriminatory ability of continuous variables and to produce
      dummy variables for use in a logistic regression analysis. Cases had a
      significantly higher body mass index, higher maximal levels of serum creatine
      kinase, and a shorter time preceding coronary intervention than controls. The
      severity of coronary atherosclerosis was similar between the 2 groups. The
      frequency distribution of ACE genotypes in cases differed from that in controls
      (II/ID/DD: 22.0%/52.6%/25.4% vs 44.1%/41.4%/14.7%, p<0.05, by the Mantel-Haenzel
      chi-square test). The ACE-D allele had additive and dominant effects with regard
      to the occurrence of significant ventricular arrhythmias after adjusting for
      other risk factors. The ACE-D allele may play a pivotal role in sudden cardiac
      death in patients with AMI.

PMID- 11446494
TI  - Circadian variation of the onset of acute myocardial infarction in the Osaka
      area, 1998-1999: characterization of morning and nighttime peaks.
AB  - The onset of acute myocardial infarction (AMI) shows characteristic circadian
      variations; that is, a definite morning peak related to biologic rhythms and a
      vague nighttime peak related to socioeconomic factors. The recent economic
      recession in Japan may change the circadian variation, especially the nighttime
      peak. This study evaluated the recent circadian variation of AMI in Osaka and
      specified the patient subgroups showing either a morning or nighttime peak
      predominantly. Of 1,609 consecutive patients with AMI registered from April 1998
      to January 2000, 1,252 whose onset of AMI was definitely identified were studied.
      The day was divided into six 4-h periods with a morning peak between 08.01 h and
      12.00h, and nighttime peak between 20.01 h and 24.00h. When subgroup analysis was
      performed, female patients aged 65 years or more showed a morning peak alone and
      male patients aged less than 65 years with an occupation and the habits of
      cigarette smoking and alcohol intake showed a nighttime peak alone. Thus, in
      Osaka nighttime socioeconomic factors may currently be more potent triggers of
      AMI than the morning surges in younger male workers who smoke and drink.

PMID- 11446495
TI  - The genetic factor in acute myocardial infarction with hypertension.
AB  - This study assessed the contribution of polymorphisms of angiotensin II (AngII)
      receptors and bradykinin B2 (BK-B2) receptor to hypertension and acute myocardial
      infarction (AMI) in a Japanese population: 150 subjects with essential
      hypertension, 150 subjects with AMI with/without hypertension, and 150 healthy,
      age- and sex-matched controls. Polymorphisms of the AngII type 1 receptor (1166
      A/C) and type 2 receptor (3123 C/A), and the BK-B2 receptor (-58T/C, exon 1) were
      analyzed and significant differences of genotypes and allelic frequencies in the
      AngII type 2 receptor C/A and BK-B2 receptor -58T/C were found between the
      essential hypertension and control subjects. Further, a significantly higher
      incidence of the C allele of the BK-B2 receptor was seen in AMI subjects with
      hypertension compared with those without hypertension. Genetic variations in the
      AngII and BK-B2 receptors could prove to be significant pathophysiological
      mechanisms affecting essential hypertension and AMI, and genetic differences
      appear to be a new risk factor for these conditions.

PMID- 11446496
TI  - Relationship between doppler-derived left ventricular diastolic function and
      exercise capacity in patients with myocardial infarction.
AB  - Doppler echocardiographic indices of left ventricular (LV) diastolic function are
      widely used to evaluate the cardiac function of patients with cardiac disease.
      However, there have been few reports about the relationship between Doppler
      indices and exercise capacity and so 44 patients with myocardial infarction were
      investigated by cardiopulmonary exercise testing and 2-D and Doppler
      echocardiography. Diastolic performance was assessed using Doppler transmitral
      flow velocity and pulmonary venous flow velocity. The ratio of peak E wave
      velocity and peak A wave velocity (E/A) correlated with peak oxygen consumption
      (peak Vo2) (R=0.72), and there was a negative correlation between the
      deceleration time of E velocity (Dct) and peak Vo2 or anaerobic threshold (AT)
      (R=-0.65, -0.62, respectively). The ratio of peak S wave velocity and peak D wave
      velocity (S/D) negatively correlated with peak Vo2 (R=-0.58). Left ventricular
      ejection fraction did not correlate to exercise capacity. These results suggest
      that the Doppler echocardiographic indices of LV diastolic function correlate
      with exercise capacity in patients with mild cardiac dysfunction.

PMID- 11446497
TI  - Improved reproducibility of intravascular ultrasound assessment of coronary in
      stent neointima with the use of an echogenic contrast agent.
AB  - The present study evaluated a new technique that has the potential to improve the
      border detection of in-stent neointima using an echogenic contrast agent during
      intravascular ultrasound (IVUS). To confirm the reproducibility of IVUS imaging
      for measuring the cross-sectional in-stent neointima area, inter- and intra
      observer variability and correlation were determined. Conventional IVUS (plain
      IVUS) and IVUS using a contrast agent (contrast IVUS) were performed in 24
      subjects 6.5+/-1.5 months after undergoing a Palmaz-Schatz coronary stent
      implant. Conventional IVUS delineated completely the in-stent neointima in 6
      subjects (25%). In the remaining 18 subjects (75%), delineation of the neointima
      was incomplete despite the use of various combinations of imaging conditions (eg,
      transmission, compress, post-process). With contrast IVUS, the boundary of the
      neointima, and therefore the neointima area, was clearly distinguishable, and
      this resulted in complete delineation of the neointima in all 24 subjects. With a
      contrast agent, inter- and intra-observer variability significantly decreased
      (0.94+/-0.69mm2 conventional IVUS vs 0.37+/-0.40mm2 contrast IVUS, p<0.001;
      0.69+/-0.56mm2 conventional IVUS vs 0.07+/-0.10mm2 contrast IVUS, p<0.0001;
      respectively). Thus, contrast IVUS provides a reproducible method for the
      quantitative analysis of in-stent neointima with excellent inter- and intra
      observer correlation.

PMID- 11446498
TI  - Doppler echocardiography-derived index of myocardial performance (TEI index):
      comparison with brain natriuretic peptide levels in various heart disease.
AB  - Plasma brain natriuretic peptide (BNP) has diagnostic and prognostic value in
      heart failure. Cardiac dysfunction varies from systolic or diastolic dysfunction
      alone to the combination of both. In the present study, Doppler echocardiographic
      parameters, including the Doppler echocardiography-derived index (TEI index),
      were compared with plasma BNP levels in 74 patients with various heart diseases.
      Blood sampling was performed before an echocardiographic examination was
      conducted. The TEI index was defined as the summation of isovolumic contraction
      and relaxation time divided by ejection time. In patients with left ventricular
      (LV) systolic dysfunction (ejection fraction <50%), the TEI index and BNP were
      increased significantly compared with patients with normal LV systolic function
      (p<0.05). Patients with a TEI index > or =0.45 showed significantly increased BNP
      levels compared with patients with a TEI index <0.45, irrespective of LV systolic
      function (241.4+/-451.2 vs 65.9+/-81.8pg/ml; p<0.05). The TEI index was
      significantly higher in patients with a BNP > or =73pg/ml than in patients with
      BNP <73pg/ml (0.57+/-0.24 vs 0.46+/-0.17; p<0.05). Other echocardiographic
      parameters did not correlate significantly with levels of plasma BNP. Of the
      echocardiographic parameters, a simple Doppler index (TEI index) that combines
      systolic and diastolic function can detect LV dysfunction in patients with high
      levels of plasma BNP in various heart diseases.

PMID- 11446499
TI  - Magnesium deficiency in patients with recent myocardial infarction and provoked
      coronary artery spasm.
AB  - This study sought to clarify the relationship between magnesium (Mg) deficiency
      and coronary artery spasm provoked by pharmacologic agents in patients with a
      recent acute myocardial infarction (AMI). Twenty-three consecutive patients
      suffering from AMI were investigated with a Mg retention test (Mg: 0.1 mmol/kg
      for 4 h) in both the acute phase (within I week (3+/-2 days) of onset) and the
      subacute phase (3-4 weeks (24+/-6 days) of the onset). Early coronary
      arteriography was performed in all patients. Coronary stenosis in the infarct
      related artery was less than 90% in all patients in the subacute phase. The spasm
      provocation test was performed in the subacute phase and coronary spasm was
      defined as transient subtotal or total occlusion in association with angina or
      electrocardiographic ST-segment deviation. Coronary artery spasm was provoked in
      only 13 of the 23 patients. Compared with the control subjects (12 patients
      without coronary artery disease or coronary spasm), the 24-h Mg retention was
      significantly higher in patients with AMI (acute phase: 78+/-27%, subacute phase:
      66+/-32%, vs control: 48+/-12%, p<0.05). In the subacute phase, the 24-h Mg
      retention decreased in patients without coronary spasm (43+/-26%), but a high
      level of Mg retention was still observed in patients with coronary spasm (84+/
      25%). There was no difference in the serum concentrations of Mg, calcium and
      phosphorus between the 2 groups on both phases. In conclusion, both Mg deficiency
      and provoked coronary artery spasm were noted in more than half of the Japanese
      patients with a recent AMI, suggesting a close association between Mg deficiency
      and AMI.

PMID- 11446500
TI  - Clinical usefulness of the combination of T-wave alternans and late potentials
      for identifying high-risk patients with moderately or severely impaired left
      ventricular function.
AB  - Ventricular tachyarrhythmia (VT) is an independent risk factor for an increased
      overall mortality in patients with impaired left ventricular (LV) function, but
      there is not an established noninvasive tool to detect such patients. The present
      study aimed to clarify the most useful noninvasive approach for identification of
      patients with moderately or severely impaired LV function complicated by VT.
      Sixty-seven patients in New York Heart Association (NYHA) classes I-III with an
      LV ejection fraction (LVEF) less than 40% and an LV end-diastolic dimension
      (LVDD) of at least 55 mm on echocardiography were enrolled. Impaired LV function
      was caused by either ischemic (n=30) or nonischemic dilated cardiomyopathy
      (n=37). T-wave alternans (TWA), QT dispersion (QTD), and late potentials (LP) on
      signal-averaged electrocardiography were sequentially determined without using
      antiarrhythmic drugs. VT was defined as more than 6 consecutive ventricular
      ectopic beats. The mean NYHA class was 1.9+/-0.7, mean LVEF was 31+/-8%, and mean
      LVDD was 65+/-10mm. A history of VT was present in 26 of the patients (39%).
      Univariate and multivariate logistic analysis showed that TWA and LP were closely
      related to VT, whereas NYHA> or =III, LVEF<30%, LVDD> or =70mm, and QTD> or =90ms
      were not. The combination of TWA and LP had the most significant value (p=0.0004,
      odds ratio=8.44) by univariate analysis, and only this combination had
      significant value in multivariate analysis (p=0.04). Therefore, the combination
      of TWA and LP could be a useful index for identifying those patients with
      impaired LV function who are at risk for VT.

PMID- 11446501
TI  - Role of alpha1-blockade in congenital long QT syndrome: investigation by exercise
      stress test.
AB  - Beta-blockade is widely reported to reduce the incidence of syncope in 75-80% of
      patients with congenital long QT syndrome (LQTS). However, despite full-dose beta
      blockade, 20-25% of patients continue to have syncopal episodes and remain at
      high risk for sudden cardiac death. In some patients refractory to beta-blockade,
      the recurrence of arrhythmias is successfully prevented by left stellate
      ganglionectomy, and also by labetalol, a nonselective beta-blockade with alpha1
      blocking action. These observations suggest that not only beta-adrenoceptors, but
      also alpha1-adrenoceptors, play an important pathogenic role, especially under
      sympathetic stimulation, in LQTS. The clinical effects of alpha1-blockade in
      congenital LQTS were investigated in 8 patients with familial or sporadic LQTS.
      Two measurements of the QT interval were taken, from the QRS onset to the T wave
      offset (QT) and from the QRS onset to the peak of the T wave (QTp). Using the
      Bruce protocol, an exercise test was performed after administration of beta
      blockade alone and again after administration of alpha1-blockade. The following
      were compared: (1) Bazzet-corrected QT (QTc) and QTp (QTpc) intervals in the
      supine and standing position before exercise and in the early recovery phase
      after exercise; and (2) the slopes (reflecting the dynamic change in the QT
      interval during exercise) of the QT interval to heart rate were obtained from the
      linear regression during the exercise test. In the supine position before
      exercise, there was no change in the QTc before or after the addition of alpha1
      blockade (498+/-23 vs 486+/-23 ms [NS]). However, in the upright position before
      exercise and in the early recovery phase after exercise, QTc was significantly
      shortened from 523+/-21 to 483+/-22ms (p<0.01), and from 521+/-30 to 490+/-39ms
      (p<0.01), respectively, by alpha1-blockade. The QTpc was unchanged in any
      situation. Consequently, QTc-QTpc was significantly shortened by alpha1-blockade
      in the upright position before exercise and in the early recovery phase after
      exercise (131+/-36 to 105+/-37ms (p<0.05), and 132+/-29 to 102+/-31 ms (p<0.01),
      respectively). The slopes of the QT interval-heart rate relation by linear
      regression became significantly steeper from -2.23+/-0.38 to -2.93+/-0.76
      (p<0.01) with the addition of alpha1-blockade. The findings suggest that the
      addition of alpha1-blockade attenuated the exercise-induced prolongation of the
      QT interval and that the rate adaptation of the QT interval to heart rate during
      exercise was improved. This indicates that additional treatment with alpha1
      blockade may be beneficial to prevent cardiac events in LQTS patients in whom
      ventricular arrhythmia is resistant to beta-blockade.

PMID- 11446502
TI  - Complement and polymorphonuclear leukocyte activation each play a role in
      determining myocardial ischemia-reperfusion injury.
AB  - Cobra venom factor (CVF) transiently activates polymorphonuclear leukocytes (PMN)
      by complement activation, followed by rapid complement depletion and gradual
      reversal of PMN activation. Utilizing these sequential changes caused by CVF, the
      individual and combined effects of complement and PMNs on myocardial infarct size
      (IS) were investigated. Rats were treated with CVF, and/or anti-PMNs. Complement
      was depleted, but circulating PMNs were being activated at 4h after CVF
      administration, and at 36h after, complement was depleted, but PMNs were in a
      near basal condition. Under anesthesia, the rats had a 30-min coronary occlusion
      followed by 6h of reperfusion. The IS was assessed by tetrazolium staining. CVF,
      as well as anti-PMNs, reduced myeloperoxidase (MPO) activity in the risk area and
      the reduced MPO resulted in a reduced IS, which was also the effect of anti-PMNs,
      but complement depletion by CVF, during which circulating PMNs were activated,
      failed to reduce the IS despite low MPO activity. These results suggest that
      complement and the condition of PMNs each play a role in determining the IS, and
      ischemic reperfusion injury might be produced even by relatively low myocardial
      MPO activity.

PMID- 11446503
TI  - Radiofrequency ablation at the coronary sinus ostium interrupts the vagal
      efferent input to the atrioventricular node in the canine heart.
AB  - The fat pad at the junction of the inferior vena cava and inferior left atrium is
      the area of convergence of vagal projections into the atrioventricular node (AVN)
      region. The present study investigated whether radiofrequency (RF) ablation
      applied to the area around the coronary sinus (CS) ostium would impair vagal
      input to the AVN in the canine heart. Twenty-four dogs were anesthetized by
      sodium pentobarbital and RF energy was delivered at 20W for 5-10s. In the
      baseline state without vagal stimulation (10Hz, 2ms), the electrophysiological
      variables did not change significantly after RF ablation. Vagally induced changes
      in the sinus cycle length and effective refractory period of the right atrium and
      left ventricle did not differ after RF ablation. However, the effects of vagal
      stimulation on the AVN function were impaired after RF ablation to the CS area
      from the ostium to 10mm within the ostium. After ablation was applied to the fast
      pathway area, the vagally induced changes in the AVN function decreased, but
      these changes were not affected after RF ablation in the slow pathway area. RF
      ablation in the vicinity of the CS would attenuate vagal input to the AVN.

PMID- 11446504
TI  - Combination of N-methyl-1-deoxynojirimycin and ischemic preconditioning markedly
      reduces the size of myocardial infarcts in rabbits.
AB  - N-methyl-1-deoxynojirimycin (NMDN), an a-glucosidase inhibitor, reduces
      myocardial infarct size by reducing the glycogenolytic rate through inhibition of
      the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart, in
      addition to possessing an antihyperglycemic action by blocking alpha-1,4
      glucosidase in the intestine. Ischemic preconditioning (PC), which markedly
      reduces the size of the myocardial infarct, is known to reduce the activity of
      phosphorylase and reduce the glycogenolytic rate. Therefore, it was hypothesized
      that a combination of pharmacological inhibition of glycogenolysis by an alpha
      1,6-glucosidase inhibitor, NMDN, and PC could markedly reduce myocardial infarct
      size more than NMDN or PC alone. Japanese white rabbits without collateral
      circulation were subjected to a 30-min coronary occlusion followed by 48-h
      reperfusion. The infarct sizes as a percentage of area at risk were significantly
      reduced by pre-ischemic treatment with either 100mg/kg of NMDN or PC of 5 min
      ischemia and 5 min reperfusion alone (15.9+/-2.0%, n=8, and 10.3+/-1.2%, n=8,
      respectively) as compared with the control (43.9+/-2.2%, n=8). However, the
      combination of 100mg/kg of NMDN and PC significantly reduced the infarct size
      (4.9+/-1.2, n=8) compared with NMDN or PC alone. Another 40 rabbits, also given
      100mg of NMDN, PC, NMDN+PC or saline before ischemia (n=10 in each group), were
      killed for biochemical analysis after 30 min of ischemia. NMDN and PC preserved
      the glycogen content and attenuated the lactate accumulation, respectively, as
      compared with the control. However, the combination of NMDN and PC preserved
      significantly more glycogen and significantly reduced lactate accumulation than
      either NMDN or PC alone. The combination of NMDN and PC markedly reduced the
      myocardial infarct size more than either process alone. The marked preservation
      of glycogen and marked attenuation of lactate accumulation by the combination of
      NMDN and PC suggest that the mechanism for this effect of NMDN+PC is related to
      the inhibition of glycogenolysis.

PMID- 11446505
TI  - Ischemic preconditioning and nicorandil pretreatment improve donor heart
      preservation.
AB  - The present study investigated the effects of ischemic preconditioning (IPC) and
      nicorandil pretreatment on myocardial storage in a donor heart preservation
      model. Isolated rat hearts were separated into groups: group 1, non
      preconditioned control group; group 2, 2.5 min of normothermic ischemia followed
      by 15 min of normothermic Langendorff perfusion (one IPC cycle); and group 3, 2
      cycles of IPC. All hearts were subsequently stored in University of Wisconsin
      solution at 4 degrees C for 2, 4 and 6h, and the concentrations of high-energy
      phosphate metabolites were measured for each time point. Heart function
      parameters (aortic flow, coronary flow and cardiac output) were measured when the
      heart was reperfused following the 2, 4 or 6 h of preservation. The effects of
      nicorandil, an ATP-sensitive potassium channel opener, on heart function
      following preservation were also evaluated. Nicorandil was injected intravenously
      before heart harvesting. The results showed that the energy status was well
      preserved in the IPC groups. The 2-cycle IPC group showed better recovery of
      heart function following preservation. Pretreatment with nicorandil also improved
      functional recovery of the heart following preservation. The present study showed
      that IPC of the rat heart resulted in improved myocardial energy metabolism and
      functional recovery after hypothermic preservation, and that nicorandil has
      potential for pharmacological preconditioning in heart preservation for
      transplantation.

PMID- 11446506
TI  - Carcinomatous lymphangitis mimicking pulmonary thromboembolism.
AB  - A 41-year-old woman was admitted with rapidly worsening dyspnea. Echocardiography
      disclosed interventricular septal flattening and a markedly decreased left
      ventricle, although left ventricular contraction remained normal. Computed
      tomography of the chest demonstrated slightly dilated main pulmonary arteries and
      fine reticulonodular densities in the lung. Examination of a transbronchial lung
      biopsy specimen revealed carcinomatous lymphangitis, and the patient died 7 days
      after admission. The clinical presentation of this patient was difficult to
      discriminate from that seen with pulmonary thromboembolism.

PMID- 11446507
TI  - Inappropriate discharges from an intravenous implantable cardioverter
      defibrillator due to T-wave oversensing.
AB  - This report describes the clinical management of 2 patients with ventricular
      fibrillation (VF) who received inappropriate shocks from an implantable
      cardioverter defibrillator (ICD) due to T-wave oversensing. Cardiac sarcoidosis
      was confirmed as the underlying heart disease in 1 patient and idiopathic dilated
      cardiomyopathy in the other. Within 2 months after ICD implantation, both
      patients received several inappropriate shocks during sinus rhythm. Stored
      electrograms showed decreased R-wave amplitudes and increased T-wave amplitudes.
      The ICD sensed both R- and T-waves as ventricular activation, which met the rate
      criteria for VF treatment. Reprogramming the sensing threshold in association
      with administration of a drug to slow the heart rate decreased the incidence of
      the inappropriate shocks in both patients, but these palliative measures did not
      completely suppress the inappropriate shocks. To avoid T-wave oversensing, the
      repositioning or adding of a sensing lead is required. The potential risk of T
      wave oversensing in ICD patients who have small R-wave amplitudes should be
      recognized.

PMID- 11446508
TI  - Life-threatening pulmonary edema following unilateral stent implantation for
      bilateral branch pulmonary stenosis: recovery after contralateral stent
      implantation.
AB  - A 13-year-old girl, who was suffering complications with bilateral pulmonary
      artery stenosis after intracardiac repair for tetralogy of Fallot, suffered life
      threatening left pulmonary bleeding and edema following inadvertent unilateral
      stent implantation for a left pulmonary stenosis. Pulmonary edema and subsequent
      hypoxia persisted despite intensive medical treatment; however, contralateral
      stent deployment resolved her symptoms quickly.

PMID- 11446509
TI  - A case of cardiomyopathy showing progression from the hypertrophic to the dilated
      form: association of Mt8348A-->G mutation in the mitochondrial tRNA(Lys) gene
      with severe ultrastructural alterations of mitochondria in cardiomyocytes.
AB  - This report describes a case of cardiomyopathy with a novel point mutation of
      mitochondrial DNA coding lysine tRNA in association with severe ultrastructural
      alterations of the mitochondria in the cardiomyocytes. Abnormalities of energy
      production and/or abnormal protein synthesis because of the mutation of
      mitochondrial DNA may have played an important role in the pathogenesis of this
      case, which showed severe cardiomyocyte degeneration and deterioration from
      hypertrophic cardiomyopathy to severe dilated cardiomyopathy.

PMID- 11446510
TI  - Antibiotic resistance with particular reference to soil microorganisms.
AB  - Evidence of increasing resistance to antibiotics in soil and other natural
      isolates highlights the importance of horizontal transfer of resistance genes in
      facilitating gene flux in bacteria. Horizontal gene transfer in bacteria is
      favored by the presence of mobile genetic elements and by the organization of
      bacterial genomes into operons allowing for the cooperative transfer of genes
      with related functions. The selective pressure for the spread of resistance genes
      correlates strongly with the clinical and agricultural overuse of antibiotics.
      The future of antimicrobial chemotherapy may lie in developing new antimicrobials
      using information from comparative functional microbial genomics to find genetic
      targets for antimicrobials and also to understand gene expression enabling
      selective targeting of genes with expression that correlates with the infectious
      process.

PMID- 11446511
TI  - Intracellular bacterial symbiosis in the genus Sitophilus: the 'biological
      individual' concept revisited.
AB  - Eukaryotic cells, as genetic entities, most often involve several physically
      associated genomes that direct the metabolic cell equilibrium. In the coleopteran
      insects of the genus Sitophilus, in addition to the nucleus and the mitochondrial
      genomes, two other intracellular bacterial genomes belonging to the alpha and the
      gamma groups of Proteobacteria are also present. Coexisting with the eukaryotic
      host cell genomes, they intervene in the physiology and reproduction of the host.
      They are both transmitted vertically to the progeny and exhibit different levels
      of symbiont integration in insects. Their coexistence within a eukaryotic cell
      system illustrates the genetic complexity of animal tissue and questions the
      concept of the 'biological individual'.

PMID- 11446512
TI  - Induction of vap genes encoded by the virulence plasmid of Rhodococcus equi
      during acid tolerance response.
AB  - The response of the intracellular pathogen Rhodococcus equi to acid shock, a
      stress potentially encountered after phagocytosis by macrophages, was analyzed.
      The wild-type and its avirulent plasmid-cured strain acquired increased acid
      tolerance during the exponential growth phase upon exposure to sublethal acid
      stress, a response referred to as the acid tolerance response. Maximal adaptation
      was observed when cells were pretreated for 90 min at pH 5.0 before exposure to
      the pH challenge. Search for plasmid-encoded proteins regulated by an acidic pH
      was performed using two-dimensional gel electrophoresis, and enabled us to detect
      several membrane and cytoplasmic proteins with altered expression during the
      adaptation phase, but none of them were plasmid-encoded. However, using a
      strategy based on plasmid-encoded gene expression, we showed that two operons
      located on the virulence plasmid of strain 85F were upregulated by acid pHs with
      a maximal induction at pH 5.0. One operon, containing vapA, was monocistronic
      whereas the other was polycistronic composed of vapD and an unknown open reading
      frame. Our combined results suggest that these genes may play an important role
      in the pathogenicity of R. equi.

PMID- 11446513
TI  - Identification and characterization of novel competence genes comA and exbB
      involved in natural genetic transformation of Pseudomonas stutzeri.
AB  - After transposon mutagenesis we identified a novel gene (comA) of Pseudomonas
      stutzeri which is essential for natural genetic transformation. The putative
      amino acid sequence is similar to ComA orthologs of other transformable bacteria
      including Neisseria gonorrhoeae (ComA), Haemophilus influenzae (Rec-2), Bacillus
      subtilis (ComEC) and Streptococcus pneumoniae (CelB). Downstream of comA two
      partially overlapping open reading frames termed exbB and exbD were found coding
      for putative proteins similar to proteins required for macromolecule uptake in
      Escherichia coli and present in other Gram-negative bacteria. Insertional
      inactivation of exbB decreased the transformability to 20% of that of the wild
      type. The binding of 3H-labeled DNA and its uptake into a DNase-resistant state
      in the comA and exbB strains were similar to the wild type, suggesting that these
      proteins are involved in a late step of transformation, presumably in the
      translocation of DNA from the periplasm into the cytosol. The question of whether
      the translocation process occurs separately from the step of single-strand
      formation is discussed.

PMID- 11446514
TI  - rrn operons in Haemophilus parainfluenzae and mosaicism of conserved and species
      specific sequences in the 16S-23S rDNA long spacer.
AB  - The mosaic organisation of short-sequence boxes was analysed in the cloned and
      sequenced long ribosomal spacer (547 bp) of Haemophilus parainfluenzae GR.
      Comparison and alignment of both the long and the short spacer were performed in
      H. parainfluenzae and H. influenzae Rd. The long spacer contained two tRNA genes
      (tRNA(Ala) and tRNA(Ile)) which are highly homologous to the corresponding genes
      found in the spacers of other species, such as Haemophilus spp., Actinobacillus
      spp., and Plesiomonas shigelloides. At the 3' end of tRNA(Ala) a putative
      ribosomal spacer loop was found, showing a strong secondary structure. Pulsed
      field gel electrophoresis (PFGE) analysis after restriction of the genome of H.
      parainfluenzae GR with I-Ceu I and subsequent polymerase chain reaction (PCR)
      analysis of PFGE-separated DNA fragments demonstrated that the H. parainfluenzae
      genome contained six operons and that the long spacer was present in three copies
      of them. Two short DNA segments were identified as being species-specific,
      allowing us to design PCR primers which were useful in the molecular
      identification of H. parainfluenzae isolates.

PMID- 11446515
TI  - Regulation of microcin C51 operon expression: the role of global regulators of
      transcription.
AB  - Expression of the microcin C51 operon in Escherichia coli cells is regulated as a
      function of the phase of growth; it is stimulated during the decelerating phase
      of growth. Using single-copy P(mcc)-lac transcriptional fusion (the promoter
      region of the microcin C51 operon fused to a promoterless lac operon in lambda
      phage), we showed that transcription from the microcin operon promoter is
      dependent on sigma(s) (RpoS) factor. However, some level of P(mcc)-lac expression
      is possible in rpoS null mutants, indicating that another sigma factor might be
      involved in transcription of the microcin C51 operon. Overproduction of sigma70
      decreased Pmcc-directed transcription, presumably as a result of competition of
      sigma factors for the limited amount of core RNA polymerase. The cyclic AMP-CRP
      complex was shown to stimulate transcription from Pmcc: the absence of CRP or
      cAMP in crp or cya mutant cells strongly decreased the level of P(mcc)-lac
      expression. The production of C51 microcin decreased or was absent in rpoS, crp
      and cya mutant cells. Leucine-responsive protein Lrp and histone-like protein H
      NS repressed P(mcc)-lac expression in the exponential and decelerating phases of
      growth. In studies of P(mcc)-lac expression in double mutant cells, we showed
      that proteins CRP, Lrp and H-NS acted in rpoS-dependent and rpoS-independent ways
      in transcription of the microcin C51 operon. Mutation hns(-) resulted in an
      increase in P(mcc)-lac expression in crp, rpoS and lrp mutant cells, as in wild
      type cells.

PMID- 11446516
TI  - NKBOR, a mini-Tn10-based transposon for random insertion in the chromosome of
      Gram-negative bacteria and the rapid recovery of sequences flanking the insertion
      sites in Escherichia coli.
AB  - We have constructed an R6K-based suicide vector that permits the random insertion
      of a mini-transposon named NKBOR into the chromosome of Gram-negative bacteria
      and the subsequent rapid cloning of sequences flanking the insertion site in
      Escherichia coli. This mini-transposon contains a conditional R6K plasmid origin
      of replication, a kanamycin resistance gene and unique restriction sites between
      the IS10 inverted repeats. NKBOR can be propagated by replication in an E. coli
      strain containing the R6K replicase pi protein. Alternatively the mini-transposon
      can be replicated in a pSC 101 derivative that is thermosensitive for its
      replication so that the mini-transposon acts as a suicide plasmid at
      nonpermissive temperatures. Efficient NKBOR transposition is ensured by
      expression of an adjacent transposase gene and has been demonstrated in E. coli,
      Klebsiella pneumoniae, and Erwinia carotovora. Sequences flanking the insertion
      sites in these strains can be rapidly recovered and identified in E. coli strains
      expressing the R6K pi protein.

PMID- 11446517
TI  - A novel gene from Myxococcus xanthus that facilitates membrane translocation of
      an extracellular endoglucanase in Escherichia coli?
AB  - Expression in Escherichia coli of the Myxococcus xanthus gene celA, which encodes
      an extracellular endoglucanase, resulted in CelA being distributed between
      cytoplasm, periplasm and membrane. The presence of an adjacent open reading frame
      downstream from the full celA gene, or the absence of a putative lipoprotein
      signal sequence, confined CelA distribution to the periplasm and membrane, or to
      the cytoplasm and periplasm, respectively.

PMID- 11446518
TI  - Pseudomonas brenneri sp. nov., a new species isolated from natural mineral
      waters.
AB  - The vernacular name 'fluorescent Pseudomonas group 97-391' was coined for a group
      of 11 strains isolated from two French natural mineral waters. All these strains
      were Gram-negative, rod-shaped and motile by means of a single polar flagellum.
      They produced fluorescent pigment (pyoverdin) on King B medium, catalase and
      cytochrome oxidase. They were not able to accumulate poly-beta-hydroxybutyrate.
      They were capable of respiratory but not fermentative metabolism. DNA-DNA
      hybridization results and DNA base composition analysis revealed that strains of
      the 'fluorescent Pseudomonas group 97-391' were members of a new species, for
      which the name Pseudomonas brenneri sp. nov. (type strain CIP 106646T) is
      proposed. The levels of DNA-DNA relatedness within this group ranged from 70 to
      100% with DeltaTm below 1 degree C. The G+C content of the DNA of the type strain
      was 58 mol%. DNA relatedness with 72 strains representing well-known or partially
      characterized species of the genus Pseudomonas (sensu stricto) was below 48%. The
      complete 16S rRNA sequence of the type strain CIP 106646T was determined and
      compared with those of the type strains of Pseudomonas species. Finally, a
      phylogenetic tree was inferred from sequence analysis and demonstrated that the
      new species fell into the 'Pseudomonas fluorescens intrageneric cluster'. The
      clinical significance of P. brenneri is unknown.

PMID- 11446519
TI  - Class II broad-spectrum mercury resistance transposons in Gram-positive bacteria
      from natural environments.
AB  - We have studied the mechanisms of the horizontal dissemination of a broad
      spectrum mercury resistance determinant among Bacillus and related species. This
      mer determinant was first described in Bacillus cereus RC607 from Boston Harbor,
      USA, and was then found in various Bacillus and related species in Japan, Russia
      and England. We have shown that the mer determinant can either be located at the
      chromosome, or on a plasmid in the Bacillus species, and is carried by class II
      mercury resistance transposons: Tn5084 from B. cereus RC607 and B. cereus VKM684
      (ATCC10702) and Tn5085 from Exiguobacterium sp. TC38-2b. Tn5085 is identical in
      nucleotide sequence to TnMERI1, the only other known mer transposon from Bacillus
      species, but it does not contain an intron like TnMERI1. Tn5085 is functionally
      active in Escherichia coli. Tn5083, which we have isolated from B. megaterium
      MK64-1, contains an RC607-like mer determinant, that has lost some mercury
      resistance genes and possesses a merA gene which is a novel sequence variant that
      has not been previously described. Tn5083 and Tn5084 are recombinants, and are
      comprised of fragments from several transposons including Tn5085, and a relative
      of a putative transposon from B. firmus (which contains similar genes to the
      cadmium resistance operon of Staphylococcus aureus), as well as others. The
      sequence data showed evidence for recombination both between transposition genes
      and between mer determinants.

PMID- 11446520
TI  - The use of fluoroquinolones as antiinfective transition-therapy agents in
      community-acquired pneumonia.
AB  - The newer quinolone antibiotics, including levofloxacin, moxifloxacin, and
      gatifloxacin, offer coverage of the likely pathogens in community-acquired
      pneumonia (CAP) and have been shown to be safe and effective treatments for CAP.
      Two of these agents, levofloxacin and gatifloxacin, have pharmacokinetic and
      antibacterial properties that are similar in both oral and intravenous
      formulations. As such, they may be excellent candidates for transition therapy
      involving early switch from intravenous to oral therapy followed by early
      hospital discharge for patients with CAP

PMID- 11446521
TI  - Introduction. Designing a transition therapy program.

PMID- 11446522
TI  - Managing antiinfective therapy of community-acquired pneumonia in the hospital
      setting: focus on switch therapy.
AB  - Targeting patients for early switch from intravenous to oral antibiotic therapy
      and early hospital discharge is an important strategy in the management of
      community-acquired pneumonia (CAP). This strategy can reduce costs due to drug
      administration and length of hospital stay. We show that switch therapy can be
      implemented safely when four criteria are met: cough and respiratory distress
      improve, fever abates for at least 8 hours, white blood cell count is returning
      to normal, and patient can take drugs orally In prospective clinical studies
      conducted at our institution, the clinical cure rate with switch therapy was 99%,
      and mean length of hospital stay was reduced by more than 2 days. Early switch,
      coupled with hospital discharge, may be possible in nearly half of all CAP
      patients. Universal use of switch therapy in the United States could result in
      the total reduction of about 440,000 hospital days annually and an overall
      savings of $400 million.

PMID- 11446523
TI  - Intravenous-to-oral transition therapy in community-acquired pneumonia: the INOVA
      Health System experience.
AB  - Economic pressures on the delivery of health care have necessitated a focus on
      reducing costs and resource utilization while maintaining or improving the
      quality of care. A growing consensus holds that switching from intravenous to
      oral therapy is a cost-effective and clinically sound approach for a
      significantly large group of patients with community-acquired pneumonia (CAP).
      Drug utilization studies within the INOVA Health System revealed that
      levofloxacin is a cost-effective alternative to ciprofloxacin in infectious
      disease and that use of risk prediction criteria can reduce inappropriate
      hospitalizations for CAP, thereby reducing costs. In addition, the INOVA
      experience demonstrates that the strategy used to implement new antibiotic
      regimens such as switch-therapy regimens is an important factor in cost
      reduction: a therapeutic interchange mandate is more successful than standard
      educational techniques in changing treatment patterns.

PMID- 11446524
TI  - A controlled trial of a critical pathway for treating community-acquired
      pneumonia: the CAPITAL study. Community-Acquired Pneumonia Intervention Trial
      Assessing Levofloxacin.
AB  - Recent clinical trials in patients with community-acquired pneumonia (CAP)
      demonstrated that switching from intravenous to oral antibiotic therapy is safe
      once clinical improvement is evident, thereby facilitating early hospital
      discharge. This study evaluated the use of a critical pathway to improve the
      efficiency of treating CAP in 1743 patients at 19 teaching and community
      hospitals in Canada. Hospitals were randomized to continue conventional
      management of CAP (10 hospitals) or implement a critical pathway (9 hospitals).
      The main clinical outcome measure was patients' scores (assessed 6 wks after
      hospital presentation) on the Short-Form 36 Physical Component Summary, a quality
      of-life questionnaire. Secondary clinical outcome measures included occurrence of
      complications, readmission rates, and mortality. The primary economic outcome
      measure was resource utilization, measured by the number of bed days/patient
      managed (BDPM). Clinical outcomes were good in both groups, with no significant
      differences between the two management strategies. However, use of the clinical
      pathway was associated with a 1.7-day reduction in BDPM and fewer admissions of
      low-risk patients.

PMID- 11446525
TI  - New directions in antiinfective therapy for community-acquired pneumonia in the
      emergency department.
AB  - The emergency department is becoming an increasingly important setting for the
      management of community-acquired pneumonia (CAP). This trend reflects the
      shortened hospital stays and decreased mortality among elderly hospitalized
      patients resulting from rapid administration of antimicrobials. In addition,
      decisions about the site of care (inpatient vs outpatient) and antimicrobial
      therapy frequently are made in the emergency department. Recent research and
      subsequent clinical guidelines may help with these decisions. For example,
      recently issued guidelines, such as those of the Infectious Diseases Society of
      America and the American Thoracic Society, suggest that selection of
      antimicrobials for CAP (which is typically empiric) should be based on the
      potential pathogens and likelihood of antimicrobial resistance. Macrolides and
      tetracyclines are recommended in younger patients with mild-to-moderate disease.
      Patients with more severe disease and those at risk for drug-resistant pathogens
      should be treated with broad-spectrum therapy, such as a newer fluoroquinolone or
      a cephalosporin plus a macrolide. When hospitalization is required, early switch
      from intravenous to oral therapy, followed by early discharge, can be a highly
      successful strategy. Antimicrobials that are available in both intravenous and
      oral formulations, such as the newer fluoroquinolones (e.g., levofloxacin and
      gatifloxacin), can simplify switch therapy For outpatients, an initial long
      acting parenteral dose of azithromycin, ceftriaxone, or levofloxacin followed by
      oral therapy is an effective protocol. In addition, use of a prediction rule to
      identify low-risk patients with CAP may help guide decisions about the need for
      hospital admission.

PMID- 11446526
TI  - The habitat of Paracoccidioides brasiliensis: how far from solving the riddle?
AB  - When trying to understand the pathophysiology of any infectious agent, one key
      piece of information is the determination of its habitat. In the case of
      Paracoccidioides brasiliensis, the precise location of the fungus' environmental
      niche remains undefined despite the efforts of various research groups. This
      review summarizes recent studies on the ecology of P. brasiliensis and certain
      facets of paracoccidioidomycosis. Studies on the juvenile form of
      paracoccidioidomycosis in children less than 13 years of age, the
      characterization of the ecological factors in the 'reservarea' where the
      infection is acquired and the presence of P. brasiliensis in the nine-banded
      armadillo (Dasypus novemcinctus), are all helping to pinpoint the microniche of
      this pathogen. The application of molecular biology techniques based on the
      amplification of nucleic acids will also hopefully help in establishing the
      precise habitat of P. brasiliensis.

PMID- 11446527
TI  - Quantitative culture of Malassezia species from different body sites of
      individuals with or without dermatoses.
AB  - Quantitative cultures were obtained using contact plates to determine whether the
      quantity and composition of Malassezia species at a given anatomic site in normal
      individuals differs from that of patients with various cutaneous dermatoses. The
      sample included 20 clinically healthy individuals (without any dermatosis) and
      110 patients with dermatoses (including 31 with atopic dermatitis [AD], 28 with
      psoriasis [PS], 28 with seborrheic dermatitis [SD] and 23 with pityriasis
      versicolor [PV]). Contact plates filled with special culture medium were used to
      obtain a quantitative culture from five body sites (scalp, forehead, arm, trunk
      and leg) of every individual. The number of cfu were recorded for every plate
      that grew Malassezia yeasts, and 3-5 colonies were isolated for identification to
      species level using microscopic, physiological and molecular characteristics. The
      mean cfu counts observed among patients with AD, PS and SD was significantly
      lower than normal control subjects (P < 0.05). The mean cfu counts from PV
      patients was not different from that of healthy control subjects. Overall, for
      all conditions considered together, the mean cfu counts in lesional sites were
      significantly lower than in non-lesional sites (P <0.05). Furthermore, the mean
      cfu counts from lesional sites in patients with AD and PS were significantly
      lower than the corresponding value in patients with PV (P <0.05). Six Malassezia
      species were recovered from the different dermatoses. Malassezia sympodialis was
      the most common species associated with AD and PV patients and healthy control
      subjects, while M. globosa was most frequently isolated from PS and SD patients.
      More than one Malassezia species was recovered at any given anatomic site from
      both controls as well as individuals with dermatoses. M. globosa was equally
      likely to be recovered from scalp, forehead and trunk, but less likely to derive
      from arms and legs. M. restricta and M. slooffiae were recovered more frequently
      from the upper body (scalp and forehead) than from the lower body. Among normal
      individuals and for patients with AD and PV, M. sympodialis was significantly
      more likely to affect the forehead than the legs.

PMID- 11446528
TI  - Identification of genes of Aspergillus fumigatus up-regulated during growth on
      endothelial cells.
AB  - Aspergillus fumigatus is an important opportunistic fungal pathogen that can
      cause acute invasive disease in neutropenic hosts. Invasive aspergillosis is
      being diagnosed with increasing frequency, and morbidity and mortality remain
      high despite prompt antifungal therapy. Because little is known about the
      virulence factors used by A. fumigatus, a tissue culture model was developed to
      mimic the interaction of the fungus with the endothelium. Differential display
      was used to compare gene expression in fungal cells grown on endothelial cells
      with that of cells grown in the absence of endothelial cell contact, and genes
      that were up-regulated were selected for analysis as putatively virulence-related
      genes. Two of these up-regulated genes were chosen for further study and were
      identified as genes encoding the regulatory subunit of cyclic adenosine
      monophosphate (cAMP)-dependent protein kinase and a member of the ras gene
      family, both of which are involved in cAMP-mediated signaling in fungi. This
      model system provides a new approach to the identification of potentially
      virulence-related genes induced in A. fumigatus by the interaction with host
      cells.

PMID- 11446529
TI  - Oroesophageal candidiasis is lethal for transgenic mice with combined natural
      killer and T-cell defects.
AB  - Germfree transgenic epsilon 26 (Tgepsilon26) mice, which express the full-length
      human CD3epsilon gene, have combined defects in natural killer (NK) cells and T
      cells were found to be extremely susceptible to oroesophageal (palate, tongue,
      esophagus) and gastric (cardia-antrum section) candidiasis. The gnotobiotic
      Tgepsilon26 mice die, apparently from severe oroesophageal candidiasis, within 2
      4 weeks after their alimentary tracts are colonized with Candida albicans. The
      Tgepsilon26 mice manifest resistance to acute systemic candidiasis (intravenous
      injection) and to systemic candidiasis of endogenous origin for the first 2 weeks
      after their alimentary tracts are colonized with C. albicans. Granulocyte
      depletion data suggest that granulocytes, in the absence of functional NK cells
      and T cells, can protect Tgepsilon26 mice from acute systemic candidiasis and
      from systemic candidiasis of endogenous origin, for at least 14 days after
      alimentary tract colonization. Granulocytes and macrophages, in the absence of NK
      cells and T cells, are unable to protect Tgepsilon26 mice from lethal
      oroesophageal candidiasis and systemic candidiasis of endogenous origin which was
      evident in moribund Tgepsilon26 mice 2-4 weeks after colonization. Thus, non-T
      cells (i.e., NK cells) and T cells play important roles in resistance to
      oroesophageal and systemic (acute and of endogenous origin) candidiasis.

PMID- 11446530
TI  - Purification and characterization of a 43.5 kDa keratinolytic metalloprotease
      from Microsporum canis.
AB  - A keratinolytic protease secreted by a feline clinical isolate of Microsporum
      canis cultivated in a broth containing feline keratin as the sole nitrogen source
      was purified from the culture filtrate by affinity chromatography on bacitracin
      agarose and by hydrophobic chromatography on octyl-agarose. The enzyme had an
      apparent molecular mass of 43.5 kDa and the pI was 7.7. It had a significant
      activity against keratin azure, elastin-Congo red and denatured type I collagen
      (azocoll). Using the latter substrate, the optimum pH was around 8 and the
      apparent optimum temperature around 50 degrees C. The protease was strongly
      inhibited by 1,10-phenanthroline, phosphoramidon and EDTA. The first 13 N
      terminal amino acid sequence showed a 61% homology with that of the extracellular
      metalloprotease of Aspergillus fumigatus and with the neutral protease I of A.
      oryzae, confirming that this 43.5 kDa keratinase is a metalloprotease. This
      keratinolytic metalloprotease could be a virulence-related factor involved in
      pathophysiological mechanisms of M. canis dermatophytosis.

PMID- 11446531
TI  - Canine paracoccidioidomycosis: a seroepidemiologic study.
AB  - Sera from 305 dogs were analyzed by enzyme-linked immunosorbent assay (ELISA) to
      determine presence of the antibody anti-gp43, which reacts to a specific antigen
      of Paracoccidioides brasiliensis. The dogs were divided into three groups
      according to their origin: urban dogs (animals with little or no contact with
      rural areas); suburban dogs (from the urban outskirts); and rural dogs. There was
      a significant difference between groups (P < 0.05). Rural dogs reacted positively
      in 89.5% of cases, followed by suburban (48.8%) and urban dogs (14.8%). There
      were no differences between male and female dogs. In an attempt to verify the
      feasibility of skin testing with gp43 to determine sensitization against P.
      brasiliensis in dogs, suburban (n = 61) and rural (n = 21) dogs were tested,
      showing positivity of 13.1 and 38.1%, respectively. Six dogs that had higher
      ELISA titers and also showed strong reactions in skin testing were killed in an
      attempt to isolate P. brasiliensis. The fungus was not detected by culture or
      histopathological analysis in these dogs, suggesting that dogs have a natural
      resistance or that they encounter an inoculum level that is insufficient to cause
      disease. These results indicate that ELISA and skin testing can be useful in the
      epidemiological study of paracoccidioidomycosis in dogs and that encounter with
      the fungus in nature is a frequent event.

PMID- 11446532
TI  - Inhibition of hyphal growth of Candida albicans by activated lansoprazole, a
      novel benzimidazole proton pump inhibitor.
AB  - The effect of activated lansoprazole (AG 2000), a novel benzimidazole proton pump
      inhibitor, against hypha formation of Candida albicans was examined in hypha
      forming medium pH 7 (HFM7) after 20 h. AG 2000, at 50-800 microM, did not inhibit
      germ tube formation. However, it inhibited elongation of germ tubes to form
      hyphae and favored conversion of germ tubes to resume yeast growth at
      concentrations of > or =200 microM. Pre-treatment of AG 2000 with a sulfhydryl
      reagent (1:1), such as 2-mercaptoethanol. blocked the inhibitory property of AG
      2000 on hypha formation.

PMID- 11446533
TI  - Morphological evidence for keratinolytic activity of Scopulariopsis spp. isolates
      from nail lesions and the air.
AB  - The morphological expression of human hair and nail invasion in vitro by 31
      isolates of nine Scopulariopsis species was studied by light microscopy on whole
      material and on semi-thin sections, as well as by transmission electron
      microscopy. Only some isolates of Scopulariopsis brumptii, S. candida, S.
      carbonaria and S. koningii were keratinolytically active. They came either from
      nail lesions or from outdoor aerosols. The most active isolate belonged to S.
      koningii and was recovered from a fingernail lesion. Both hair and nail
      degradation followed the biochemical and morphogenetic model described by the
      authors for other keratinolytic fungi.

PMID- 11446534
TI  - Sporothrix schenckii thermo-intolerant mutants losing fatal visceral infectivity
      but retaining high cutaneous infectivity.
AB  - Four mutants of the Sporothrix schenckii lung isolate IFM 41598 were isolated by
      their inability to form colonies on a Sabouraud glucose agar plate incubated at
      37 degrees C for 4 days. In contrast to the parent IFM 41598, these thermo
      intolerant mutants were all defective in producing fatal visceral infections in
      mice, even though they retained infectivity in footpad tissues with a small
      fungal inoculum (approximately equals 10 cfu).

PMID- 11446535
TI  - Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance.
AB  - We have cloned and sequenced the Aspergillus fumigatus CYP51 gene which encodes
      the target of azole antifungal agents, namely cytochrome P450 sterol 14alpha
      demethylase. Since A. fumigatus is intrinsically resistant to the widely used
      azole fluconazole, we compared its predicted CYP51 sequence to the CYP51
      sequences from fluconazole-susceptible and resistant Candida albicans. This
      analysis generated specific hypotheses regarding the basis for A. fumigatus
      fluconazole resistance; in particular, A. fumigatus residue Ile301 corresponds to
      C. albicans residue Thr315 which is mutated to Ala in resistant strains and is
      proposed to hydrogen bond with the sterol substrate.

PMID- 11446536
TI  - A pediatric survey for the National Highway Traffic Safety Administration:
      emergency medical services system re-assessments.
AB  - Emergency medical services for children, or EMSC, is still a relatively
      underdeveloped component of most state and local EMS systems. Advocacy and
      funding for EMSC from the federal EMSC Program, availability of many useful EMSC
      products, and the rapidly enlarging literature in EMSC have created heightened
      awareness and interest in improving systems for pediatric emergency, trauma, and
      critical care. The new National Highway Traffic Safety Administration (NHTSA) EMS
      Technical Assistance (TA) re-assessment program, the second version of the
      successful original TA Program from 1988 to 1996, provides an ideal opportunity
      for state EMS professionals to evaluate EMSC capabilities and to integrate new
      EMSC products and services. The history of the TA Program reflects the evolution
      of EMS itself and indicates a historical inattention to children's issues, but re
      assessment TA teams now have much useful intervening EMSC history to draw upon
      and a clear philosophical mandate to integrate children more fully in EMS system
      planning and management. In order to facilitate state-of-theart reviews of EMSC
      within state EMS systems, a pediatric survey for the NHTSA re-assessments is
      presented. The survey, developed with the input of EMS administrators and
      physicians and approved by the National Association of State EMS Directors,
      follows the original ten-component model for EMS system review. It is intended
      for optional use within the overall EMS review process.

PMID- 11446537
TI  - Cardiac arrest management.
AB  - Approximately 1,000 people in the United States suffer cardiac arrest each day,
      most often as a complication of acute myocardial infarction (AMI) with
      accompanying ventricular fibrillation or unstable ventricular tachycardia.
      Increasing the number of patients who survive cardiac arrest and minimizing the
      clinical sequelae associated with cardiac arrest in those who do survive are the
      objectives of emergency medical personnel. In 1990, the American Heart
      Association (AHA) suggested the chain of survival concept, with four links--early
      access, cardiopulmonary resuscitation (CPR), defibrillation, and advanced care-
      as the way to approach cardiac arrest. The recently published International
      Resuscitation Guidelines 2000 of the AHA have addressed advances in our
      understanding of the chain of survival. While the chain of survival concept has
      withstood a decade of scrutiny, there are only a few scientifically rigorous
      research studies that support changes in prehospital patient care. Additional
      research efforts carried out in the prehospital setting are needed to support the
      concepts included in the chain of survival for cardiac arrest patients.
      Participants at the second Turtle Creek Conference, a meeting of experts in the
      field of emergency medicine held in Dallas, Texas, on March 29-31, 2000,
      discussed these and other issues associated with prehospital emergency care in
      the cardiac arrest patient. This paper addresses a number of the issues
      associated with each of the links of the chain of survival, the evidence that
      exists, and what should be done to achieve the clinical evidence needed for true
      clinical significance. Also included in this paper are the consensus statements
      developed from small discussion groups held after the main presentation. These
      comments provide another perspective to the problems and to possible approaches
      to deal with them.

PMID- 11446538
TI  - The locations of nonresidential out-of-hospital cardiac arrests in the City of
      Pittsburgh over a three-year period: implications for automated external
      defibrillator placement.
AB  - OBJECTIVES: To determine the locations of nonresidential out-of-hospital cardiac
      arrests (OHCAs) in the City of Pittsburgh and to determine whether there are
      "high-risk" locations that might benefit from placement of automated external
      defibrillators (AEDs). METHODS: This was a retrospective case review of paramedic
      calls for OHCA over a three-year period, in a mid-sized northeastern city.
      Cardiac arrests that were traumatic or for which the patients were dead on
      arrival (DOA) or had advanced directives for no resuscitation were excluded.
      Cardiac arrests that occurred in a public location (i.e., not a private
      residence) were categorized. RESULTS: A total of 971 OHCAs occurred in the City
      of Pittsburgh from January 1, 1997, to December 31, 1999. Of these, 575 (59%)
      occurred in private residences, and 396 (41%) occurred in nonresidential
      locations. Fifteen locations had at least one cardiac arrest per year for three
      years, accounting for 166 (43%) of the total nonresidential OHCAs. Twelve
      locations had two arrests during the three-year period, accounting for 24 (6%) of
      the total nonresidential OHCAs. One hundred ninety-four locations had a single
      episode of cardiac arrest, accounting for 51% of the OHCAs. Nursing homes and
      dialysis centers accounted for 178 (94%) OHCAs in the 27 locations that had two
      or more cardiac arrests. A local sports/events complex (Three Rivers Stadium) was
      the only other single location to have more than two cardiac arrests in the three
      year study period, with a total of three. However, events at this complex are
      routinely staffed by paramedics equipped with defibrillators. CONCLUSION: The
      majority of nonresidential OHCAs occur as singular, isolated events. Other than
      nursing homes and dialysis centers, there were no identifiable high-risk
      locations for nonresidential OHCA within the City of Pittsburgh.

PMID- 11446539
TI  - The effects of prehospital advanced life support drug treatment on patient
      improvement and in-hospital utilization.
AB  - OBJECTIVE: There is little published evidence to support the benefits of
      prehospital drug administration by ambulance personnel in reducing subsequent
      hospital utilization by the medical patients receiving such drugs. The authors
      studied the outcome of patients treated by Ontario's Emergency Health Services
      "Symptom Relief Drug Program," which was developed to relieve patient symptoms in
      the field for specific medical emergencies. METHODS: A retrospective study
      spanning a three-year period from January 1996 to December 1998 was undertaken in
      a mid-sized southern Ontario community. From a review of ambulance call reports
      (ACRs), eligible patients were recruited by mail and divided into two groups:
      those treated before the introduction of the program (pre) and those treated
      after (post). Out-of-hospital data were retrieved from ACRs and in-hospital data
      were gathered from medical chart reviews. Outcomes included emergency department
      (ED) length of stay (LOS), frequency of admissions, and departmental use.
      Secondary endpoints included differences in prehospital improvement, ED
      interventions, and ambulance scene times. RESULTS: For the unpaired analysis, 406
      patients provided consent (pre: 215 vs post: 191). Ambulance time on scene was
      longer in the post group, 14.2 minutes (95%CI 13.7-14.8), versus the pre group,
      12.3 minutes (95% CI 11.7-12.9), p < 0.001. A larger proportion of patients
      receiving prehospital drug treatment were judged to have improved on ED arrival
      (pre: 19.5% vs post: 48.2%, chi2 p < 0.0001). The ED LOSs did not differ between
      groups (pre: 206.9 min, 95% CI 185.9-230.4, vs post: 220.9 min, 95% CI 196.9
      247.7, p = 0.42) but were shorter within the post group for hypoglycemic patients
      receiving glucagon. The overall proportion of admissions was significantly lower
      in the post group (pre: 145 [67.4%] vs post: 102 [54.3%], chi2 p < 0.01), and
      this was driven by chest pain patients. CONCLUSIONS: The lower rate of admissions
      for chest pain patients is the first published evidence of prehospital drug
      treatment's reducing hospital utilization in a sub-group of such medical
      patients. The "Symptom Relief Drug Program" is effective in improving patients'
      field conditions and can decrease ED LOS in hypoglycemic persons receiving
      glucagon injections. More outcome research pertaining to ambulance-administered
      prehospital drug treatment is warranted.

PMID- 11446540
TI  - Characteristics of fatal ambulance crashes in the United States: an 11-year
      retrospective analysis.
AB  - BACKGROUND: Ambulance crashes have become an increasing source of public concern.
      Emergency medical services directors have little data to develop ambulance
      operation and risk management policies. OBJECTIVE: To describe fatal ambulance
      crash characteristics, identifying those that differentiate emergency and
      nonemergency use crashes. METHODS: This was a retrospective analysis of all fatal
      ambulance crashes on U.S. public roadways reported to the Fatality Analysis
      Reporting System (FARS) database from 1987 to 1997. Main outcome measures were 42
      variables describing crash demographics, crash configuration, vehicle
      description, crash severity, and ambulance operator and vehicle occupant
      attributes. RESULTS: Three hundred thirty-nine ambulance crashes caused 405
      fatalities and 838 injuries. These crashes occurred more often between noon and 6
      PM (39%), on improved (99%), straight (86%), dry roads (69%) during clear weather
      (77%), while going straight (80%), through an intersection (53%), and striking
      (81%) another vehicle (80%) at an angle (56%). Most crashes (202/339) and
      fatalities (233/405) occurred during emergency use. These crashes occurred
      significantly more often at intersections (p < 0.001), at an angle (p < 0.001),
      with another vehicle (p < 0.001). Most crashes resulted in one fatality, not in
      the ambulance. Thirty pedestrians and one bicyclist comprised 9% of all
      fatalities. In the ambulance, most serious and fatal injuries occurred in the
      rear (OR 2.7 vs front) and to improperly restrained occupants (OR 2.5 vs
      restrained). Sixteen percent of ambulance operators were cited; 41% had poor
      driving records. CONCLUSIONS: Most crashes and fatalities occurred during
      emergency use and at intersections. The greater burden of injury fell upon
      persons not in the ambulance. Rear compartment occupants were more likely to be
      injured than those in the front. Crash and injury reduction programs should
      address improved intersection control, screening to identify high-risk drivers,
      appropriate restraint use, and design modifications to the rear compartment of
      the ambulance.

PMID- 11446541
TI  - Comparison of perceived pain with different immobilization techniques.
AB  - OBJECTIVE: To compare the locations and severities of pain generated by a hard
      wooden spine board vs a soft vacuum mattress splint on immobilized volunteers.
      METHODS: This was a prospective randomized crossover study conducted in an
      emergency medical services (EMS) classroom within a university teaching hospital.
      Participants were 18 healthy volunteers with no history of acute or chronic back
      pain, pregnancy, or recent analgesic use. The subjects were placed in one of
      three immobilization boards (hard spine board and two different vacuum splint
      models, identified as red and blue) for 60 minutes. At 0, 30, and 60 minutes the
      subjects rated their pain at multiple locations on their body using a visual
      analog scale (VAS). After a two-day washout period, this procedure was repeated
      on a different board and later a third board until all the subjects had been
      tested on all three boards. RESULTS: Although many pressure point locations were
      studied, only three had results that appeared statistically significant: the
      occiput, lower back, and sacrum. The hard spine board had higher mean pain scores
      as well as a higher percentage of subjects who reported any pain when compared
      with the two vacuum mattress splints. Mean scores for the 30- and 60-minute times
      were: occiput 2.06 and 2.78 for the hard board compared with 0.78 and 0.56 for
      red and 0.44 and 0.67 for blue; lower back 1.39 and 1.44 for the hard board
      compared with 0.28 and 1.11 for red and 0.06 and 0.17 for blue; and sacrum 1.56
      and 2.06 for the hard board compared with 0.33 and 0.39 for red and 0.89 and 1.06
      for blue. CONCLUSION: The hard-board method of spinal immobilization generates
      higher self-reported pain scale scores than the two vacuum mattresses.

PMID- 11446542
TI  - Comparison of capillary and venous glucose measurements in healthy volunteers.
AB  - BACKGROUND: Out-of-hospital (OOH) emergency personnel measure serum glucose in
      order to determine the need for dextrose therapy. Most devices that measure serum
      glucose are designed to use capillary blood obtained from a finger puncture.
      However, OOH emergency personnel often use venous blood obtained during
      intravenous line (IV) placement to determine serum glucose. OBJECTIVE: To compare
      capillary and venous glucose measurements. METHODS: This prospective study used
      healthy, non-fasting volunteers. Simultaneous venous and capillary blood samples
      were obtained from each subject. Glucose levels were measured using a glucometer
      designed for capillary samples. The capillary and venous measurements were
      compared using a Pearson correlation coefficient. Power analysis revealed that
      the study had the ability to detect a difference of 15 mg/dL. RESULTS: Ninety
      seven volunteers (56 males, 41 females) with a mean age of 37 +/- 11.9 years were
      enrolled. The mean capillary and venous glucose values were 104.5 +/- 20.7 mg/dL
      and 109.7 +/- 22.4 mg/dL, respectively. The Pearson correlation coefficient was
      0.24. CONCLUSIONS: The correlation between venous and capillary blood glucose
      measurements is relatively poor in this group of healthy volunteers. Further
      research must be conducted on patients at risk for abnormal blood glucose.

PMID- 11446543
TI  - Outcome study of minors after parental refusal of paramedic transport.
AB  - OBJECTIVE: Patient refusal of paramedic transport against medical advice (AMA)
      has significant medical-legal implications. Previous studies have investigated
      patient outcomes after refusal of transport, but none has focused on these events
      in minors. This study was performed to evaluate the outcomes of this patient
      population after refusal of transport as well as the significance of base
      hospital physician discussion with parents in the decision to refuse transport.
      METHODS: This was a retrospective telephone follow-up survey involving parents of
      minors for whom transport was refused after accessing emergency medical services
      (EMS) via the 911 system. Data were initially obtained from paramedic run records
      and each family was subsequently contacted by telephone and surveyed with regard
      to their experiences with the field medics in addition to the medical follow-up
      sought for their child and patient outcomes. RESULTS: Eighty-nine patients met
      criteria for survey. Telephone contact was made with 44 parents, of whom 32 (73%
      of those contacted, 36% overall) participated. Twenty-seven (84%) received
      medical follow-up, either at an emergency department or in a private physician's
      office. Most patients (89%) who were evaluated and/or treated by a physician were
      subsequently released, while three children were admitted to the hospital, all
      three with respiratory or cardiac chief complaints. CONCLUSIONS: Children whose
      parents refused EMS transport received medical follow-up in the majority of
      cases, with a small group requiring admission.

PMID- 11446544
TI  - Prehospital and hospital-based health care providers' experience with a human
      patient simulator.
AB  - OBJECTIVES: To ascertain the level of acceptance of a human patient simulator as
      a training tool among a diverse group of health care providers. Secondary
      objectives were to elucidate its most useful aspects for training and find ways
      to improve upon the simulation experience. METHODS: A satisfaction survey was
      conducted regarding the use of a human patient simulator from July 1999 to
      February 2000. The survey consisted of five questions with a five-point Likert
      scale (5 being the most favorable score) and three questions that asked for
      qualitative written feedback on the simulator experience. The survey was handed
      to 78 consecutive participants immediately after their experiences and collected
      immediately after it was filled out to ensure a 100% response rate to the overall
      survey. Qualitative responses were placed into categories by theme, and a sum was
      calculated for each category. RESULTS: There was a high level of acceptance for
      simulation training among this diverse group, with Likert scores for the first
      two questions regarding general satisfaction of 4.74 +/- 0.126 (n = 77) and 4.77
      +/- 0.126 (n = 78). Regarding the usefulness of each specific area of simulator
      training, the scores were 4.53 +/- 0.153 (n = 78) for patient assessment, 4.55 +/
      0.182 (n = 47) for treatment options, and 4.70 +/- 0.125 (n = 63) for response
      to treatment. There were 49 positive comments and nine negative comments. Realism
      (n = 26) and the ability to see response to treatment (n = 12) were the two most
      common positive comments. Negative comments focused on logistics of the simulator
      lab (n = 4) rather than the simulator itself. CONCLUSIONS: In this sample,
      prehospital and hospital-based health professionals were accepting of human
      patient simulation as a new teaching tool with multiple useful applications.

PMID- 11446545
TI  - Patient nontransport. National Association of EMS Physicians/American College of
      Emergency Physicians Joint Position Paper.

PMID- 11446546
TI  - Alternate ambulance transportation and destination. National Association of EMS
      Physicians/American College of Emergency Physicians Joint Position Paper.

PMID- 11446547
TI  - The role of the certified flight paramedic (CFP) as a critical care provider and
      the required education.

PMID- 11446548
TI  - Refusal of base station physicians to authorize narcotic analgesia.

PMID- 11446549
TI  - A near-fatal case of long QT syndrome in a teenaged male.

PMID- 11446550
TI  - Prehospital airway management with the laryngeal mask airway in polytraumatized
      patients.

PMID- 11446551
TI  - Cases of aminophylline and vasopressin use after failed prehospital resuscitation
      of cardiac arrest.

PMID- 11446552
TI  - Out-of-hospital cardiac arrest in Hong Kong.
AB  - OBJECTIVES: To evaluate the effectiveness of the local emergency medical services
      system in resuscitation of out-of-hospital cardiac arrest and identify areas for
      improvement. METHODS: This was a prospective descriptive study of adults with
      nontraumatic out-of-hospital cardiac arrest treated in the three accident &
      emergency departments that serve the whole of Hong Kong Island from March 15,
      1999, to October 15, 1999. Patient characteristics, circumstances of cardiac
      arrest, final outcomes, and response times of the ambulance service were recorded
      according to the Utstein style. RESULTS: Three hundred twenty patients were
      included. There was male predominance, and the mean age was 71.5 years. The
      majority of cardiac arrests occurred at patients' homes. In 57.5% of cases the
      arrest was not witnessed. The bystander cardiopulmonary resuscitation (CPR) rate
      was 15.6%. The most common electrocardiographic (ECG) rhythm at scene was
      asystole. Ventricular fibrillation or pulseless ventricular tachycardia
      constituted 14.1%. The average call to dispatch interval was 1.04 minutes. The
      average call to CPR interval was 9.82 minutes. The average total prehospital
      interval was 27.55 minutes. The overall immediate survival rate was 14.1% and the
      rate of survival to hospital discharge was 1.25%. CONCLUSION: The prognosis of
      out-of-hospital cardiac arrest in Hong Kong was dismal. Every link in the chain
      of survival has to be improved.

PMID- 11446553
TI  - Emergency medical services and cultural determinants of an emergency in Karachi,
      Pakistan.
AB  - OBJECTIVES: The study was conducted to understand the prehospital system in
      Karachi, the mode of transport that adult inpatients use to reach the emergency
      departments (EDs), and the barriers to the use of ambulances. METHODS: The study
      consisted of two parts. The first part involved interviewing the administrators
      of major ambulance services in Karachi. The second part consisted of a structured
      interview of randomly selected adult inpatients admitted to one government and
      one private hospital. RESULTS: Seven ambulance service administrators were
      interviewed. The interviews revealed that ambulances in Karachi are mainly
      involved in transporting patients from hospital to hospital or to home. A large
      number of calls are for transporting dead bodies. A total of 92 patients were
      interviewed (58 male, 34 female). Admission complaints included abdominal pain
      (22), blunt trauma (11), penetrating trauma (3), chest pain (6), shortness of
      breath (4), hematemesis (3), acute focal weakness (4), high fever (4), and other
      (32). The most common mode of transport to the ED was taxi (53, 58%), followed by
      private car (21, 23%). Specific reasons for not using ambulances included a
      perception that the patient was not sick enough (34, 45%), slow response of the
      ambulance services (17, 23%), not knowing how to find one (8, 11%), and the high
      cost (6, 8%). CONCLUSION: In case of a medical emergency, most people in Karachi
      do not use ambulances. The reasons for this low usage include not only poor
      accessibility, but also cultural barriers and lack of education in recognition of
      danger signs.

PMID- 11446554
TI  - Profile of the prehospital system in Madagascar.
AB  - OBJECTIVE: To delineate the present characteristics of emergency medical services
      (EMS) on the island of Madagascar. METHODS: This was a retrospective study of
      ambulance runs over a five-year period. The island covers 587,041 square
      kilometers with a population of 15 million, of whom 78% live in rural areas.
      RESULTS: Madagascar has 0.13 EMS workers per 1,000 people in urban areas,
      compared with 0.001 EMS workers per 1,000 people in rural areas. The urban
      physician/population ratio is 1 per 8,160, while in rural areas the ratio is
      1/30,000. There is no "911" dispatching system. The EMS system offers transport
      services in 90% of ambulance runs. Ambulance calls are dispatched by police and
      fire departments in 80% of cases and by private calls in the remaining 20%.
      Madagascar has a telephone/population ratio of 1 per 239. Each vehicle is staffed
      by two emergency medical technicians (EMTs) who are paid by local hospitals and
      clinics that operate under a medical director. Urban EMS covers an average radius
      of 100 km, in contrast to the community-based rural EMS that serves a radius of
      only 25 km. The EMS system receives critically ill patients in 35% of its runs,
      obstetrical emergencies in 30%, surgical emergencies in 25%, and pediatric
      emergencies in the remaining 10%. CONCLUSION: This study shows that urban EMS is
      more organized, has a better-developed infrastructure, and has more personnel
      than its counterparts in rural areas. Future work will determine the impact of a
      rising population shift from rural to urban areas on this evolving EMS system.

PMID- 11446555
TI  - No pain, no gain?

PMID- 11446556
TI  - Paramedic training in research methods.

PMID- 11446557
TI  - Treatment of painful osteoporotic vertebral fractures with percutaneous
      vertebroplasty or kyphoplasty.
AB  - Vertebral fracture is the most common complication of osteoporosis. It results in
      significant mortality and morbidity, including prolonged and intractable pain in
      a minority of patients. Vertebroplasty and kyphoplasty, procedures that involve
      percutaneous injection of bone cement into a collapsed vertebra, have recently
      been introduced for treatment of osteoporotic patients who have prolonged pain
      (several weeks or longer) following vertebral fracture. To determine the details
      of the procedures and to gather information on their safety and efficacy, we
      performed a MEDLINE search using the terms 'vertebroplasty' and 'kyphoplasty.' We
      reviewed reports of these procedures in patients with osteoporosis. We
      supplemented the articles found with other papers known to the authors and with
      presentations at national meetings. Randomized trials of vertebroplasty and
      kyphoplasty have not been reported. Case reports suggest that these procedures
      are associated with pain relief in 67% to 100% of cases. Short-term
      complications, mainly the result of extravasation of cement, include increased
      pain and damage from heat or pressure to the spinal cord or nerve roots. Proper
      patient selection and good technique should minimize complications, but rarely,
      decompressive surgery is needed. Long-term benefits have not yet been shown, but
      potentially include prevention of recurrent pain at the treated level(s) with
      both procedures, and, with kyphoplasty, reversal of height loss and spinal
      deformity, an improved level of function, and avoidance of chronic pain and
      restriction of internal organs. Possible long-term complications, again not fully
      evaluated, include local acceleration of bone resorption caused by the treatment
      itself or by foreign-body reaction at the cement-bone interface, and increased
      risk of fracture in treated or adjacent vertebrae through changes in mechanical
      forces. Controlled trials are needed to determine both short-term and long-term
      safety and efficacy of vertebroplasty and kyphoplasty. Both procedures may be
      useful for osteoporotic patients who have prolonged pain following acute
      vertebral fracture. Until there is conclusive evidence for efficacy and long-term
      safety, these procedures should be done only in carefully selected patients, only
      by experienced operators with appropriate high-quality imaging equipment, and
      ideally at centers that are participating in controlled trials.

PMID- 11446558
TI  - Standardization of bone mineral density at femoral neck, trochanter and Ward's
      triangle.
AB  - The International Committee for Standards in Bone Measurement (ICSBM) has
      published standardization formulas for total hip bone mineral density (BMD). In
      many applications, however, BMD of hip subregions, such as femoral neck (FN),
      trochanter (TR), and Ward's triangle (WT), are commonly measured. This paper
      addresses whether the standardization formulas for total hip BMD can be
      adequately used for hip subregions. We used data from 100 healthy women, from 20
      to 80 years old, who had hip BMD measured in both the total hip and hip
      subregions by a Hologic QDR 2000, a Lunar DPX, and a Norland XR26 Mark II. The
      same women were used by ICSBM for the standardization of total hip BMD. In
      addition, we used data of 3139 patients from a clinical trial to validate our
      results. We derived standardization formulas for FN, TR, and WT using the same
      statistical method as that used for total hip BMD. We applied both total hip
      calibration formulas and subregion-specific formulas to the data and compared the
      corresponding effect. We found that the total hip calibration formulas can
      partially reduce BMD differences between the Hologic and Lunar as well as the
      Lunar and Norland scanners in hip subregions, but increase differences between
      the Hologic and Norland scanners. The subregion calibration formulas are most
      appropriate for calibrating subregion BMD values and their absolute changes, and
      should be adopted. Standardization is unnecessary for BMD percentage changes in
      our clinical trial data.

PMID- 11446559
TI  - Changes in bone and calcium metabolism following hip fracture in elderly
      patients.
AB  - Although hip fracture is one of the most common causes of acute immobilization in
      elderly patients, little is known about the influence of immobilization on
      changes in bone and calcium metabolism following this event. We therefore
      compared serum biochemical indices of bone and calcium metabolism in 20 elderly
      subjects with hip fracture with those measured in 20 healthy age-matched
      controls. Rankin scores, a measure of functional dependence with 0 representing
      independence and 5 representing total dependence, were assigned. We also examined
      serial changes in these biochemical indices from shortly following the fracture
      to the early recovery period. Ionized calcium, intact parathyroid hormone (PTH),
      intact bone Gla protein (BGP), pyridinoline cross-linked carboxyterminal
      telopeptide of type I collagen (ICTP), 25-hydroxyvitamin D (25-OHD), and 1,25
      dihydroxyvitamin D (1,25-[OH]2D) were measured. One week after the fracture, mean
      serum concentrations of calcium and ICTP were elevated in correspondence to
      degree of immobilization (mean Rankin score; 4.4), while serum concentrations of
      BGP, PTH, 25-OHD, and 1,25-[OH]2D were depressed. Rankin score (mean: 4.4)
      correlated positively with ICTP and negatively with BGP at this time. At 2
      months, calcium and ICTP elevation decreased and BGP, PTH and 1,25-[OH]2D were
      less depressed, coinciding with a decline in Rankin score from 4.2 to 2.2.
      Indices were further improved at 3 months (mean Rankin score, 1.3), with calcium
      and BGP returning to normal. We concluded that increased bone resorption, and
      decreased bone formation, and hypercalcemia are present by 1 week following the
      hip fracture, and some resorption increase persists for at least 3 months. These
      changes could explain in part the high risk of another hip fracture.

PMID- 11446560
TI  - Behavior of phalangeal bone ultrasound in normal women with relation to gonadal
      status and body mass index.
AB  - The behavior of phalangeal bone ultrasound was studied, measured by amplitude
      dependent speed of sound (Ad-SOS) in meters per second, in 324 normal women (mean
      age 48.9 +/- 13.7 years) classified by gonadal status (premenopausal,
      perimenopausal and postmenopausal) and body mass index (BMI, thin, normal,
      overweight and obese). Ad-SOS differed significantly with gonadal status and BMI
      (p<0.0001 for all). In the overall group of women, Ad-SOS correlated negatively
      with age (r=-0.84, p<0.0001), weight (r=-0.16, p<0.005), BMI (r=-0.27, p<0.0001),
      and tartrate-resistant acid phosphatase concentration (TRAP) (r=-0.35, p<0.0001).
      The negative correlation remained significant in the groups separated by gonadal
      status, but to a lesser extent. After adjusting for confounding variables such as
      age and weight, Ad-SOS was dependent on age (but not on weight or BMI) in the
      overall group of women and in the gonadal status groups. In conclusion, Ad-SOS
      values differed significantly with gonadal status and BMI, and correlated
      negatively with TRAP. The plot of Ad-SOS against age differed significantly with
      gonadal status as well as BMI.

PMID- 11446561
TI  - Multisite quantitative ultrasound: precision, age- and menopause-related changes,
      fracture discrimination, and T-score equivalence with dual-energy X-ray
      absorptiometry.
AB  - This study evaluated the clinical utility of a new multisite ultrasound device
      capable of measuring speed of sound (SOS) at the phalanx, radius, tibia and
      metatarsal. The in vitro and in vivo short- and long-term precision were
      evaluated, reference data were collected for 409 healthy white women (236
      premenopausal and 173 postmenopausal), and age and menopause related changes were
      calculated using linear regression. Fracture discrimination was evaluated using
      109 women with vertebral fractures and the age-adjusted odds ratios calculated
      for each standard deviation decrease in SOS measurement. Correlations between SOS
      measurements and spine and femur bone mineral density (BMD) were calculated. T
      score equivalence with BMD was also investigated together with the prevalence of
      osteoporosis as defined by the WHO criteria. The in vivo short-term precision
      standardized in T-score units ranged from 0.14 to 0.33 and long-term standardized
      precision was 0.35-0.65. Postmenopausal age-related bone loss expressed as the
      annual change in T-score ranged from 0.040 to 0.089 for SOS and 0.053 to 0.066
      for BMD, whilst menopause-related annual loss ranged from 0.036 to 0.094 for SOS
      and 0.050 to 0.074 for BMD. Correlations between the different SOS sites ranged
      from r = 0.24 to 0.55, and between SOS and BMD from r = 0.12 to 0.47. The odds
      ratio (and 95% confidence intervals) for fracture per 1 SD decrease in SOS were
      2.0 (1.22 to 3.23) for the phalanx; 1.5 (1.01 to 2.24) for the metatarsal; 1.4
      (1.03 to 1.99) for the radius and 1.2 (0.87 to 1.66) for the tibia. Odds ratios
      for BMD in the same population ranged from 2.6 to 4.8 (1.70 to 8.29). The
      prevalence of osteoporosis as defined by T = <-2.5 in the age range 60-69 ranged
      from 7.1% to 20.6% for SOS and 6.4% to 12.1% for BMD. In conclusion, this study
      demonstrated that multisite ultrasound has adequate precision for investigating
      skeletal status, is capable of differentiating between pre- and postmenopausal
      women and women with vertebral fractures, has a T-score equivalence similar to
      that of dual-energy X-ray absorptiometry (DXA), and appears to be a promising new
      technique for evaluating skeletal status at clinically relevant sites.

PMID- 11446562
TI  - Anabolic effect of long-term estrogen replacement on bone collagen in elderly
      postmenopausal women with osteoporosis.
AB  - Estrogen has been shown to stimulate osteoblasts in cell culture and increase
      bone formation in animal models. Such an anabolic effect of estrogen replacement
      therapy (ERT) would be beneficial to postmenopausal women with osteoporosis.
      Hence, we assessed the total collagen content and collagen crosslink maturity in
      iliac crest bone biopsy from 18 such women before and after 6 years of higher
      dose ERT. These results were compared with the serum estradiol level and bone
      mineral density (BMD). Total collagen content of both cortical and cancellous
      bone increased, showing a median (95% CI) percent change of 6.7 (0.3-14.2) and
      25.6 (13.5-33.8), respectively. Increase in collagen synthesis was supported by a
      rise in intermediate crosslinks in both cortical and cancellous bone, and mature
      crosslinks in cortical bone only. At the same time, BMD showed a substantial rise
      both at the lumbar spine and proximal femur with a median (95% CI) percent change
      of 28.6 (19.8-37.3) and 14.5 (8.4-20.7), respectively. Serum estradiol and BMD
      results correlated with cortical bone collagen levels. Our results suggest that
      long-term higher-dose ERT has a therapeutic role due to its anabolic effect on
      bone in postmenopausal women with osteoporosis.

PMID- 11446563
TI  - Does the combination of quantitative ultrasound and dual-energy X-ray
      absorptiometry improve fracture discrimination?
AB  - The widespread availability of quantitative ultrasound (QUS) and X-ray
      absorptiometry densitometers raises the question of whether a combination of QUS
      and bone mineral density (BMD) measurements could provide a clinically useful
      method of enhancing the prediction of fracture risk. The aim of this study was to
      examine whether a combination of axial BMD and calcaneal QUS measurements can
      enhance fracture discrimination compared with either method alone. The study
      population consisted of 154 postmenopausal women with a history of atraumatic
      fracture at the spine, hip or forearm and 221 healthy postmenopausal women with
      no clinical risk factors for osteoporosis. Subjects had dual-energy X-ray
      absorptiometry (DXA) measurements of the lumbar spine (LS), femoral neck (FN) and
      total hip (THIP) and calcaneal broadband ultrasound attenuation (BUA) and speed
      of sound (SOS) measurements on the Hologic Sahara (SAH) and Osteometer DTUone
      (DTU). Z-scores were calculated using the mean and SD obtained from the healthy
      postmenopausal group. Logistic regression analysis yielded odds ratios for BMD
      measurements at the LS, FN and THIP of 2.2, 2.2 and 2.3, respectively. The odds
      ratios obtained for QUS measurements ranged from 2.5 for DTU BUA to 3.3 for SAH
      SOS. While these odds ratios for QUS measurements were higher than those obtained
      for BMD measurements, the differences were not statistically significant. When
      the odds ratios for QUS were adjusted for BMD at the spine and hip, the odds
      ratios remained significant in all cases indicating that QUS and BMD variables
      contribute independently to fracture discrimination. When the BMD-adjusted odds
      ratios were compared with those for QUS alone, they were slightly lower but not
      significantly so. When the QUS measurements were adjusted for THIP BMD, the odds
      ratios for QUS tended to be lower than when adjusted for LS and FN BMD. The Z
      scores for each of the QUS measurement variables were combined with spine or hip
      Z-scores. Logistic regression analysis of the QUS and BMD combined Z-scores
      yielded slightly higher odds ratios of approximately 3.1 (compared with 2.9
      obtained for QUS alone) and increases in the area under the curve of
      approximately 2%. However, these increases were not clinically significant. In
      conclusion, the combination of axial BMD and calcaneal QUS measurements did not
      significantly improve fracture discrimination compared with either method alone.

PMID- 11446564
TI  - Effects of 8 years of treatment with tibolone 2.5 mg daily on postmenopausal bone
      loss.
AB  - The objective of this study was to assess the long-term effects of tibolone 2.5
      mg daily (Livial; Organon) on bone mineral density in recently postmenopausal
      women. An 8-year, open, nonrandomized, prospective study was designed to compare
      the effects of tibolone 2.5 mg daily (n = 59) with an untreated control group (n
      = 51). The subjects of this study were 110 recently postmenopausal women (6-36
      months since last menstrual period). The main outcome measures were bone mineral
      density of the spine and femur, measured by dual-energy X-ray absorptiometry, and
      assessment of biochemical markers of bone metabolism. After 8 years of tibolone
      use, the mean (+/- SEM) increase in bone mineral density compared with baseline
      was 4.1% +/- 0.8% (p<0.0001) in the spine and 4.6% +/- 1.8% (p = 0.015) in the
      femoral neck. Over the same period, bone mineral density in the control group
      decreased in the spine by -7.5% +/- 1.1%, (p<0.0001) and in the femur by -6.7% +/
      1.2% (p<0.0001). The bone resorption marker, calcium/creatinine ratio, decreased
      in the tibolone group but not in the control group. Serum bone formation markers
      decreased (alkaline phosphatase) or stayed approximately the same (osteocalcin)
      in the tibolone group. Adherence was high, with 58% (34 of 59) of the tibolone
      group continuing treatment for 8 years. We conclude that tibolone 2.5 mg daily
      prevents bone loss in the lumbar spine and femoral neck over 8 years and
      adherence to treatment is high. The greater bone density compared with untreated
      women would be expected to reduce the risk of bone fractures.

PMID- 11446565
TI  - Bone disease after liver transplantation: a long-term prospective study of bone
      mass changes, hormonal status and histomorphometric characteristics.
AB  - After liver transplantation there is a high incidence of fractures, with
      important rates of bone loss during the first months. However, the long-term
      evolution of bone mass and metabolism parameters have been scarcely studied. In
      order to determine the incidence and risk factors involved in the development of
      skeletal fractures and to analyze the long-term evolution of bone mass, bone
      turnover and hormonal status after liver transplantation, a 3-year prospective
      study was performed in 45 patients following liver transplantation. Serum
      osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and
      testosterone levels (men), and bone mass at the lumbar spine and femur were
      measured before and sequentially at different time points during 3 years. Spinal
      X-rays were obtained during the first year. Histomorphometric analysis of bone
      biopsies obtained in 24 patients within the first 12 hours after surgery and 6
      months after transplantation was performed. Fifteen patients (33%) developed
      fractures after liver transplantation, and pre-transplant risk factors for
      fractures were age and low bone mass (odd's ratio for osteoporosis, 95%
      confidence interval: 5.69, 1.32-24.53). Serum PTH, osteocalcin, 25-OH D,
      testosterone and creatinine levels increased after transplantation. Moreover, PTH
      correlated with creatinine and osteocalcin values. Bone mass decreased during the
      first 6 months and reached baseline values at the lumbar spine the second year,
      with posterior significant recovery at the femoral neck. Long term evolution of
      femoral neck BMD correlated with PTH levels. Six months after transplantation
      bone histomorphometric data showed an increase in bone formation parameters.
      After liver transplantation there is a high incidence of fractures, specially in
      elderly patients and those with osteoporosis. Bone mass decreased in the short
      term period and improved, initially at the lumbar spine and later at the femur,
      according to histomorphometric evidences of an increase in bone formation. The
      increase in creatinine values induces a secondary hyperparathyroidism that
      influences the changes in femoral bone mass. Treatment of osteoporosis shortly
      after liver transplantation may be important in the prevention of bone fractures,
      particularly in patients with low bone mass.

PMID- 11446566
TI  - Diet acids and alkalis influence calcium retention in bone.
AB  - The urine-acidifying properties of food constituents depend on their content of
      non-oxidizable acids or precursors. Acidifying constituents such as animal
      proteins may negatively affect calcium metabolism and accelerate bone resorption,
      thus representing an aggravating factor for osteoporosis. This four-period,
      double-crossover study investigated whether a diet intervention specifically
      focused on acid load could modify calcium metabolism in humans. Eight healthy
      volunteers underwent a four-day metabolic preparation with two types of diets,
      one rich in acid ash-forming nutrients, and one providing base-forming nutrients
      (including bicarbonate-rich mineral water), both having similar contents of
      calcium, phosphate, sodium, proteins and calories. On the fourth day, a single
      oral dose of 1 g calcium was given, either as carbonate or as gluconolactate.
      Serial blood and urine samples revealed that the diet affected blood pH (average
      difference 0.014, p=0.002) and urine pH (average difference 1.02, p<0.0001) in
      the expected direction, but had no influence on the absorption of the calcium
      supplement. The acid-forming diet increased urinary calcium excretion by 74% when
      compared with the base-forming diet (p<0.0001), both at baseline and after the
      oral calcium load, and C-telopeptide excretion by 19% (p=0.01), suggesting a
      skeletal origin for the excess calcium output. This observation confirms that
      renally excreted acids derived from food influence calcium metabolism, and that
      alkalizing nutrients inhibit bone resorption. Further studies are needed to
      determine the clinical impact of dietary counseling for avoiding diet acids as a
      preventive measure against osteoporosis.

PMID- 11446567
TI  - Comparison of two methods for measuring ultrasound properties of the heel in
      postmenopausal women.
AB  - Combined indices of ultrasound measurements have been proposed, such as
      "stiffness index" (SI) for the Lunar Achilles+ and 'quantitative ultrasound
      index' (QUI) for the Hologic Sahara ultrasound devices. We used the Bland and
      Altman approach and the kappa (kappa) score (classifying women by tertile,
      independent of age) to compare these methods. We studied 105 postmenopausal women
      (ages 57 to 88 years). We measured the heel (in duplicate) using both devices.
      Single lumbar spine (LS) bone mineral density (BMD) measurements were also made
      using the same two manufacturers' densitometers. QUI values were higher than SI
      values with a mean difference of 2.4 units (95% CI, 1.5-3.2). This difference in
      SI and QUI was most marked at higher ultrasound values (r = 0.61, p<0.0001). The
      kappa score between SI and QUI was 0.69 (95% CI, 0.57-0.80). When we calculated
      the kappa scores based on the mean of duplicate SI and QUI measurements, the
      kappa score increased to 0.90 (95% CI, 0.77-0.94). Lunar DPX LS-BMD values were
      higher than Hologic QDR 1000/W LS-BMD values with a mean difference of 0.18 g/cm2
      (95% CI, 0.17-0.19). The difference between the machines was most marked at
      higher BMD values (r = 0.38, p<0.001). The kappa score between the DPX and QDR
      1000/W was good (kappa = 0.79, 95% CI = 0.66-0.88), and was similar to the
      agreement of SI and QUI. Based on a single measurement, some women would be
      classified in different tertiles using the two heel ultrasound machines (about
      20%). However, this is not significantly greater than the misclassification rate
      using two machines to measure spinal BMD (about 15%). Although there are
      significant differences between SI and QUI measurements, the misclassification
      rates are similar to those observed measuring LS-BMD using two different
      manufacturers' DXA machines. The misclassification rate using quantitative
      ultrasound improves when based on duplicate measurements.

PMID- 11446568
TI  - Changes in body composition as determinants of longitudinal changes in bone
      mineral measures in 8 to 26-year-old female twins.
AB  - Between 1990 and 1998, we conducted a longitudinal study of 286 female twins aged
      8 to 25 years at baseline (60 monozygotic (MZ) pairs, 44 dizygotic (DZ) pairs and
      78 unpaired twins), measured on average 2.4 times (range 2-6) with an average of
      1.8 years between measurements (range 0.7-6.7 years). Areal bone mineral density
      (ABMD) at the lumbar spine, total hip and femoral neck, total body bone mineral
      content (BMC), total body soft tissue composition (lean mass and fat mass) were
      measured by dual-energy X-ray absorptiometry, and height and menarchial status
      were also recorded. Median annual changes in height were negligible at 4 years
      post-menarche. During the 'linear growth' period up to 4 years post-menarche,
      ABMD at the lumbar spine, total hip and femoral neck increased with annual change
      in lean mass by 1.7 (S.E.0.1), 1.4 (0.1) and 1.0 (0.1) percent per kilogram per
      year, respectively (all p<0.001), independently of changes in fat mass or height.
      During the 'post-linear growth' period, ABMD at the total hip and femoral neck
      increased with annual change in fat mass by 0.3 (0.1) and 0.5 (0.1) percent per
      kilogram per year (all p < 0.01), independent of change in lean mass. Annual
      changes in total body BMC were associated with annual changes in lean mass (1.9
      (0.2) percent per kilogram), in fat mass (1.3 (0.2) percent per kilogram) and in
      height (0.7) (0.2) percent per centimeter) during linear growth, and in fat mass
      (1.0 (0.1)) and lean mass (0.6 (0.1)) percent per kilogram post-linear growth
      (all p < 0.001). We conclude that changes in bone mineral measures are strongly
      associated with changes in lean mass during linear growth, while post-linear
      growth, changes in fat mass are the predominant, although weaker, predictor.
      These findings suggest that the strong cross-sectional association between bone
      mineral measures and lean mass is established during growth and development, and
      that fat mass emerges as a more powerful determinant of bone change in healthy
      adult females.

PMID- 11446569
TI  - Responding to Meyer et al. Factors associated with mortality after hip fracture.
      Osteoporos Int 2000; 11:228-32.

PMID- 11446570
TI  - Hepatitis B outbreak in a state correctional facility, 2000.
AB  - On March 31, 2000, acute hepatitis B was confirmed serologically in a 34-year-old
      man (index patient) who had been incarcerated for 2.5 years at a high-security
      state correctional facility and who presented to the facility medical unit with
      jaundice and abnormal liver enzymes. He reported having unprotected sex with his
      cellmate as his only risk factor for infection during the 6 months preceding his
      illness. Serologic testing of the 21-year-old cellmate confirmed that he had
      chronic hepatitis B virus (HBV) infection. He reported no history of symptoms
      compatible with hepatitis and was previously unaware of his chronic infection,
      but he did report having unprotected sex with the index patient and two
      additional inmates in the dormitory (dorm Y). On May 15, 2000, the state's
      department of health and department of corrections and CDC initiated an
      investigation to identify additional cases and determine risk factors for HBV
      infection. This report summarizes the results of the investigation, which
      identified additional cases of HBV infection in this correctional facility and
      underscores the need to implement hepatitis B vaccination in correctional
      facilities.

PMID- 11446571
TI  - Influenza and pneumococcal vaccination levels among persons aged > or = 65 years-
      United States, 1999.
AB  - Annual influenza epidemics have resulted in an average of >18,000 deaths and
      48,000 pneumonia and influenza hospitalizations among older persons in the United
      States (1). In 1998, an estimated 3400 older persons died from bacteremic
      pneumococcal pneumonia, a common complication of influenza, or from other forms
      of invasive pneumococcal disease (2 ). A 2000 national health objective included
      increasing influenza and pneumococcal vaccination levels to > or = 60% among
      noninstitutionalized, high-risk persons, including those aged > or = 65 years
      (3). To assess progress toward this objective, data were analyzed from the 1999
      Behavioral Risk Factor Surveillance System (BRFSS) for persons aged > or = 65
      years. This report summarizes the results of that analysis, which indicated that
      prevalence of influenza vaccination during the 1998-99 influenza season exceeded
      the objective nationally and in 48 of 52 reporting areas; however, influenza
      vaccination levels may have reached a plateau. Prevalence among older persons who
      had ever received pneumococcal vaccination exceeded the national objective in
      only eight states. To reach the 2010 national objective of > or = 90% influenza
      and pneumococcal vaccination among this population, new strategies and additional
      resources to implement adult vaccination activities may be needed.

PMID- 11446572
TI  - Routinely recommended HIV testing at an urban urgent-care clinic--Atlanta,
      Georgia, 2000.
AB  - In 1993, CDC recommended that hospitals and associated clinics in areas with high
      human immunodeficiency virus (HIV) prevalence offer HIV testing routinely to all
      patients aged 15-54 years (1). Although voluntary routine screening among
      hospitalized (2) and emergency department patients (3) can identify many
      undiagnosed HIV-infected persons, few screening programs have been implemented in
      these settings. A 1997 study at Grady Memorial Hospital, Atlanta, Georgia, found
      that nearly two thirds of inpatients newly diagnosed with acquired
      immunodeficiency syndrome (AIDS) had received medical care within the Grady
      health system during the 12 months preceding admission (4 ); these previous
      encounters were missed opportunities for earlier diagnosis of HIV. In response to
      the 1997 study, investigators studied routinely recommending HIV testing to
      patients presenting to the urgent-care clinic, an ambulatory clinic that provides
      episodic medical care to indigent and low income adults. This report summarizes
      the results of that study in which, compared with 1999 when testing was based on
      symptoms or risk behaviors, more patients were tested for HIV, more HIV
      infections were detected, and more infected persons learned their diagnosis and
      entered into care. These results reflect the benefits of recommending HIV testing
      routinely to patients in medical facilities located in areas with high HIV
      prevalence.

PMID- 11446573
TI  - The effects of competition and competitiveness on cardiovascular activity.
AB  - Cardiovascular activity was measured at resting baseline and in response to a car
      racing game, undertaken in competition or in cooperation with an experimenter, or
      individually. Competitiveness and win and goal orientations were assessed by
      questionnaire. Competition provoked increases in blood pressure and heart rate,
      and a significant shortening of the preejection period, an index of enhanced beta
      adrenergic influences on the heart. The cooperation task was largely without
      effect, and although the solo task affected cardiovascular activity, it did so to
      a lesser extent and much less consistently than did the competition task. The
      three task conditions, then, were largely distinguishable by their capacity to
      activate beta-adrenergic processes. Participants high in competitiveness and
      desire to win showed higher blood pressure reactions and greater shortening of
      the preejection period to competition than those low in these characteristics.

PMID- 11446574
TI  - Sequence-sensitive subcomponents of P300: topographical analyses and dipole
      source localization.
AB  - P300 amplitude and reaction time (RT) are strongly affected by the sequence of
      events preceding the eliciting stimulus. Sommer, Leuthold and Soetens (1999)
      found that robust sequential effects in P300 amplitude could be dissociated from
      more variable sequential effects in RTs. However, global changes in P300
      amplitude and topography gave rise to the suggestion that sequential effects are
      specific for a subcomponent of P300 that is separate from and anterior to the
      classical parietal P300. Here, confirming evidence for dissociable subcomponents
      of P300 is reported from two experiments. Independent component analysis
      separated a centrally distributed sequence-sensitive subcomponent from a more
      parietal subcomponent. Subsequent dipole source analysis indicated a deep mesial
      source for the sequence-sensitive subcomponent. Overlap with reafferent
      somatosensory activity appears to be responsible for an apparent lateralization
      of this component towards the hemisphere ipsilateral to the responding hand.

PMID- 11446575
TI  - The processing of sound duration after left hemisphere stroke: event-related
      potential and behavioral evidence.
AB  - The ability of left-hemisphere stroke patients (n = 8) and healthy control
      subjects (n = 8) to process sounds preattentively and attentively was studied by
      recording auditory event-related potentials (ERPs) and behavioral responses. For
      the right-ear stimulation, the mismatch negativity (MMN) was significantly
      smaller in the patients than control subjects over both hemispheres. For the left
      ear stimuli, the MMN was significantly smaller in the patient group than in the
      control group over the left hemisphere, whereas no group differences were
      obtained over the right hemisphere. In addition, the N1 amplitude was reduced
      bilaterally for the right-ear stimulation (with the reduction being larger over
      the left hemisphere), whereas no significant effects on the N1 amplitude were
      found for the left-ear stimulation. Behaviorally, the patients detected
      significantly fewer deviant tones than did the control subjects irrespective of
      the stimulated ear. The present results thus suggest that the long-latency ERPs
      can be used to probe such auditory processing deficits that are difficult to
      define with behavioral measures. Especially by recording MMN to monaural stimuli,
      the discrimination accuracy can be separately determined for the left and right
      temporal lobes.

PMID- 11446576
TI  - Inhibition of pericranial muscle activity, respiration, and heart rate enhances
      auditory sensitivity.
AB  - We investigated whether previously observed inhibition of pericranial
      electromyographic (EMG) activity, respiration, and heart rate during sensory
      intake processes improves auditory sensitivity. Participants had to detect weak
      auditory stimuli. We found that EMG activity in masticatory and lower facial
      muscles, respiration, and heart rate were more strongly inhibited when stimulus
      intensity was gradually lowered to threshold level whereas EMG of upper facial
      muscles progressively increased. Detection of near-threshold stimuli was
      inversely related to prestimulus EMG levels in masticatory and lower facial
      muscles. In two additional experiments, it was investigated whether steady,
      voluntary contractions negatively influence auditory sensitivity. As expected,
      contraction of zygomaticus produced an increase in auditory threshold in
      comparison with contraction of corrugator or first dorsal interosseus. It is
      concluded that attention to external stimuli is accompanied by quieting of those
      somatic activities that produce internal noise or are accompanied by impaired
      middle ear transmission of auditory stimuli.

PMID- 11446577
TI  - Gastric myoelectrical and autonomic cardiac reactivity to laboratory stressors.
AB  - We evaluated the effects of two laboratory stressors (speech preparation and
      isometric handgrip) on gastric myoelectrical and autonomic cardiac activity, and
      the extent to which autonomic responses to these stressors and somatization
      predict reports of motion sickness during exposure to a rotating optokinetic
      drum. Both stressors prompted a decrease in preejection period (PEP) and
      respiratory sinus arrhythmia (RSA), and an increase in a dysrhythmic pattern of
      gastric myoelectrical activity, termed gastric tachyarrhythmia. Stressor-induced
      decreases in RSA and higher somatization scores predicted increased reports of
      motion sickness during drum rotation. These results demonstrate that laboratory
      stressors concurrently affect gastric myoelectrical activity and autonomic
      control of the heart, and that stressor-induced decreases in RSA and higher
      levels of somatization predict motion sickness susceptibility.

PMID- 11446578
TI  - Long-term habituation of the speech-elicited mismatch negativity.
AB  - A significant issue in the use of the mismatch negativity evoked potential (MMN)
      concerns its low signal-to-noise ratio (SNR). One can improve the noise level by
      increasing the number of samples included in the averaged response. However,
      improvement achieved in this way assumes that the signal, the MMN, remains stable
      for extended test times, an assumption which has not been tested. If the MMN is
      not stable, or exhibits habituation over the test session, then SNR would be
      adversely affected. MMN response magnitude was measured in 5-min intervals over
      the course of a test session in response to various speech syllable contrasts.
      Significant long-term habituation of MMN was observed for all three subject
      populations tested: young adults, school-age children, and guinea pigs. The time
      course of the habituation and the stimulus conditions under which it occurs have
      important implications for research and clinical applications of the MMN.
      Recording procedures that minimize habituation effects may be used to advantage
      to improve the signal-to-noise ratio of the MMN.

PMID- 11446579
TI  - Intraindividual analysis of instantaneous heart rate variability.
AB  - We examined the use and potential of quantifying instantaneous heart rate
      variability (HRV) using a joint time-frequency and time-domain methods. These new
      techniques are promising, because they provide tools to quantify nonstationary,
      beat-by-beat changes in HRV components, and are therefore flexible with respect
      to the design of experimental protocols. A smoothed pseudo-Wigner-Ville
      distribution (SPWVD) and a time-domain index using polynomial filtering produced
      fairly coherent estimates of band-specific HRV amplitudes, whereas SPWVD yielded
      additional information on the frequency characteristics of HRV. Instantaneous HRV
      appeared to have a complex and a frequency-specific relationship to cardiac
      activity and electrodermal activity, It is concluded that the time-frequency
      analysis of HRV is a very promising method for mapping transient changes in the
      frequency and amplitude characteristics of cardiac dynamics.

PMID- 11446580
TI  - Attentional stages of information processing during a continuous performance
      test: a startle modification analysis.
AB  - This study of 31 college students employed the startle eye-blink modification
      (SEM) technique to index both early and later stages of attentional processing
      during a memory-load version of the Continuous Performance Test (CPT).
      Participants viewed a series of digits and pressed a button after the digit 7 of
      each 3-7 sequence. A startling noise burst was presented either 120 or 1,200 ms
      following three preselected prepulses: target (3), nontarget (non-3 and non-7
      digits), or target plus distractor (3 and simultaneous tone distractor). Greater
      startle inhibition occurred 120 ms following target and target-plus-distractor
      prepulses compared with nontargets, indicating early selective attention. No
      difference was observed between SEM during target and target-plus-distractor
      prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the
      three prepulse types produced nondifferential inhibition, suggesting that
      modality-specific selective attention occurs in anticipation of the presentation
      of the next CPT prepulse. These findings indicate that SEM distinguishes between
      different early selective attention and later anticipatory attention subprocesses
      underlying the CPT.

PMID- 11446581
TI  - Systemic overperfusion and resting blood pressure.
AB  - During psychosocial stressors, individuals with mildly elevated resting blood
      pressures (BP) exhibit cardiac output (CO) that is in excess of metabolic demand
      (i.e., systemic overperfusion). The present study used the "additional" CO method
      to assess whether individuals in the high average BP range also exhibit systemic
      overperfusion at rest. Healthy young adult males (N = 48), divided into "high
      average" and "low average" groups using resting BP, participated in an active
      coping task. Consistent with past research, the high average group evidenced
      higher levels of additional CO than did the low average group during both
      baseline and task periods. More importantly, the high average group also
      exhibited significant amounts of additional CO at rest, whereas the low average
      group did not. These results may help to advance our understanding of the process
      by which systemic overperfusion may contribute to the development of elevated BP.

PMID- 11446582
TI  - Manipulation of frontal EEG asymmetry through biofeedback alters self-reported
      emotional responses and facial EMG.
AB  - Individual differences in resting asymmetrical frontal brain activity have been
      found to predict subsequent emotional responses. The question of whether frontal
      brain asymmetry can cause emotional responses has yet to be addressed.
      Biofeedback training designed to alter the asymmetry of frontal brain activity
      was therefore examined. Eighteen right-handed female participants were randomly
      assigned to receive biofeedback training designed to increase right frontal alpha
      relative to left frontal alpha (n = 9) or to receive training in the opposite
      direction (n = 9). Five consecutive days of biofeedback training provided signals
      of reward or nonreward depending on whether the difference between right (F4) and
      left (F3) frontal alpha exceeded a criterion value in the specified direction.
      Systematic alterations of frontal EEG asymmetry were observed as a function of
      biofeedback training. Moreover, subsequent self-reported affect and facial muscle
      activity in response to emotionally evocative film clips were influenced by the
      direction of biofeedback training.

PMID- 11446583
TI  - Event-related brain potentials evoked by verbs and nouns in a primed lexical
      decision task.
AB  - We investigated whether verbs and nouns evoke comparable behavioral and N400
      effects in a primed lexical decision task. Twenty-nine students were tested, 13
      in a pilot study in which only response times and error rates were collected and
      16 in a study in which ERPs were recorded from 124 scalp electrodes. Stimuli were
      noun-noun and verb-verb pairs with the targets bearing either a strong, a
      moderate, or no semantic association to the prime or being a pseudoword.
      Behavioral data revealed comparable priming effects for both word categories.
      These proved to be independent from the SOA (250 and 800 ms) and they followed
      the well-known pattern of decreasing response times and error rates with
      increasing relatedness between target and prime. ERPs revealed pronounced N400
      effects for both word categories with a larger amplitude for noun than for verb
      pairs. A systematic analysis of topographic differences between noun- and verb
      evoked ERPs and N400 effects, respectively, gave no convincing support to the
      hypothesis that the two word categories activate distinct neuronal networks.

PMID- 11446584
TI  - Four-week test-retest stability of individual differences in the saccadic CNV,
      two saccadic task parameters, and selected neuropsychological tests.
AB  - The aim of the present study was the comparative assessment of the 4-week test
      retest stabilities of the saccadic CNV (sCNV) and saccadic reaction times (SRT)
      during the execution of pro- and antisaccades, as well as the stability of RT
      during execution of two neuropsychological tests of alertness and S-R
      incompatibility. Prosaccades were elicited under the 200-ms gap and overlap
      conditions, antisaccades under the overlap condition (64 trials each). The EEG
      was recorded from 25 channels with a DC amplifier (MES, Munich). Data of 20
      healthy participants were statistically analyzed. We found high test-retest
      correlations for all SRT (.76 < or = r(tt) < or = .88) and neuropsychological
      (.62 < or = r(tt) < or = .88) measures. For the sCNV, coefficients ranging
      between .58 (pro/gap) and .77 (anti/overlap) were obtained. Whereas SRT were
      significantly faster during the second than during the first session, group means
      for the saccadic CNV were stable across the sessions. Our results suggest high 4
      week stability of individual differences in SRT, and moderate to good stabilities
      of saccadic CNV amplitudes. Our results recommend these "traitlike" measures to
      be used in individual differences research.

PMID- 11446585
TI  - Modulation of the human nociceptive flexion reflex across the cardiac cycle.
AB  - Carotid baroreceptor stimulation has been shown to dampen pain. This study
      tested, in 40 normotensive adults, the hypothesis that pain is lower during
      systole when arterial baroreceptor stimulation is maximal than diastole when
      stimulation is minimal. The sural nerve was stimulated electrocutaneously to
      obtain a nociceptive flexion reflex (NFR) threshold, and then stimulation was
      delivered for 28 trials at 100% NFR threshold at seven intervals after the R
      wave. Nociceptive responding was indexed by electromyographic (EMG) activity
      elicited in the biceps femoris. Significant variations in EMG activity occurred
      across the cardiac cycle, with less activity midcycle, indicating that the NFR
      response was attenuated during systole compared to diastole. Stimulation of
      baroreceptors by natural changes in blood pressure during the cardiac cycle
      dampened nociception, and accordingly, the data support the arterial baroreflex
      mechanism of hypertensive hypoalgesia.

PMID- 11446586
TI  - Affective startle modulation in anticipation and perception.
AB  - Startle modulation was investigated as participants first anticipated and then
      viewed affective pictures in order to determine whether affective modulation of
      the startle reflex is similar in these different task contexts. During a 6-s
      anticipation period, a neutral light cue signaled whether the upcoming picture
      would portray snakes, erotica, or household objects; at the end of the
      anticipatory period, a picture in the signaled category was viewed for 6 s. Male
      participants highly fearful of snakes were recruited to maximize emotional
      arousal during anticipation and perception. Results indicated that the startle
      reflex was potentiated when anticipating either unpleasant (phobic) or pleasant
      (erotic) pictures, compared to neutral stimuli, whereas during perception,
      reflexes were potentiated when viewing unpleasant stimuli, and reduced when
      viewing pleasant pictures. The startle reflex is modulated by hedonic valence in
      picture perception, and by emotional arousal in a task context involving picture
      anticipation.

PMID- 11446587
TI  - Is there pre-attentive memory-based comparison of pitch?
AB  - The brain's responsiveness to changes in sound frequency has been demonstrated by
      an overwhelming number of studies. Change detection occurs unintentionally and
      automatically. It is generally assumed that this brain response, the so-called
      mismatch negativity (MMN) of the event-related brain potential or evoked magnetic
      field, is based on the outcome of a memory-comparison mechanism rather than being
      due to a differential state of refractoriness of tonotopically organized cortical
      neurons. To the authors' knowledge, however, there is no entirely compelling
      evidence for this belief. An experimental protocol controlling for refractoriness
      effects was developed and a true memory-comparison-based brain response to pitch
      change was demonstrated.

PMID- 11446588
TI  - Best minimally modified antisense oligonucleotides according to cell nuclease
      activity.
AB  - Minimally modified oligonucleotides belong to the second-generation antisense
      class. They are phosphodiester oligonucleotides with a minimum of
      phosphorothioate linkages in order to be protected against serum and cellular
      exonucleases and endonucleases. They activate RNase H, have weak interactions
      with proteins, and have thus a better antisense efficiency. Two of them have been
      designed from an all-phosphorothioate antisense oligonucleotide directed against
      mdrl-expressing cells. They are protected against serum and cellular enzymatic
      degradation by the self-forming hairpin d(GCGAAGC) at their 3'-end and by
      judiciously located phosphorothioate residues, depending on the cellular
      composition in exonucleases or endonucleases. Besides their already demonstrated
      ability to cleave pyrimidine sites, endonucleases show some specificity for CpG
      sites. Their activity is hindered if specific sites are involved in secondary
      structure as hairpin.

PMID- 11446589
TI  - Inhibition of human DNA topoisomerase I by new DNA minor groove ligands:
      derivatives of oligo-1,3-thiazolecarboxamides.
AB  - A series of novel thiazole-containing oligopeptides (oligo-1,3
      thiazolecarboxamides) interesting specifically with the minor groove of DNA was
      shown to inhibit human DNA topoisomerase I (topo I). Inhibitory effects of
      thiazole-containing oligopeptides (TCO) increase with the number of thiazole
      units in such compounds. Inhibitory properties of TCO containing 3 or 4 thiazole
      units were shown to be 3-10 times better than those of the well-known natural
      antibiotic, distamycin A containing pyrrole rings. The structure of various
      additional groups attached to the N-terminus and C-terminus of TCO had no
      significant effect on TCO interaction with the complex of DNA and topo I. TCO
      were shown to be capable of binding with double-stranded DNA (dsDNA), and the
      majority of TCO analyzed were more effective in binding with dsDNA than
      distamycin A. Possible reasons for the different effects of distamycin A and TCO
      on the reaction of relaxation catalyzed by topo I are discussed.

PMID- 11446590
TI  - High-purity preparation of a large DNA dumbbell.
AB  - We report on the efficient biochemical synthesis of a large DNA dumbbell starting
      from a pair of short DNA hairpins with long single-stranded tails of arbitrary
      sequence. The DNA dumbbell is obtained by enzymatic ligation yielding a 94-bp
      duplex stem closed at both termini by single-stranded loops of 5 nt. Following
      ligation, all unligated precursors and monoligated by-products were multiply
      biotinylated via nick-translation or primer-extension or both. Thus, they could
      readily be removed from the DNA dumbbell preparation by a mild biomagnetic
      separation procedure. The closed conformation of the purified DNA dumbbell was
      verified by its altered gel mobility as compared with unligated or monoligated
      samples and by an exonuclease assay. Considering the promising therapeutic
      potential of DNA dumbbells, the developed biosynthetic approach could be used for
      high-purity preparation of longer, covalently closed DNA decoys.

PMID- 11446591
TI  - Toxicity and toxicokinetics of a phosphorothioate oligonucleotide against the c
      myc oncogene in cynomolgus monkeys.
AB  - A 2-week toxicity and toxicokinetic study of a 15-mer phosphorothioate
      oligonucleotide, INX-3280, against the c-myc oncogene was performed in cynomolgus
      monkeys. As this oligonucleotide readily adopts an aggregate structure, a
      quadruplex, which may be associated with adverse physiologic effects, this study
      was performed using INX-3280 that had been converted to its monomeric form.
      Animals received intravenous (i.v.) infusions of monomeric INX-3280 three times
      per week for 2 weeks at doses of 3 or 15 mg/kg per administration. The monkeys
      were examined for clinical signs: changes in hematology, serum chemistry,
      coagulation, and urinalysis parameters; complement activation; macroscopic
      findings at necropsy; and histopathologic alterations. In addition, the
      toxicokinetics of INX-3280 were evaluated, using a validated HPLC assay, after
      the first and last (sixth) doses. No treatment-related clinical signs of any
      adverse effects were observed, and there were no test article-related changes in
      hematology, serum chemistry, or complement activation parameters. The only
      alteration in clinical pathology parameters was a minor (30%) prolongation of the
      activated partial thromboplastin time (aPTT), reflecting slight inhibition of the
      intrinsic coagulation pathway, which was less than that reported with other
      oligonucleotides given at similar doses. Treatment-related histopathologic
      alterations consisted of characteristic accumulation of basophilic material in
      the cytoplasm of tubular epithelial cells in the kidney, resident macrophages in
      the lymph nodes, and Kupffer cells in the liver. These changes were graded as
      minimal in all cases. The basophilic material is believed to reflect accumulation
      of the oligonucleotide or metabolites or both. The pharmacokinetic parameters of
      INX-3280 were identical on the first and sixth administrations and were similar
      to those reported for other phosphorothioate oligonucleotides. Maximum
      concentration (Cmax) values for INX-3280 (101-119 microg/ml) were in excess of
      the threshold plasma concentrations reported to trigger complement activation by
      phosphorothioate oligonucleotides. It is concluded that the safety profile of
      monomeric INX-3280 in cynomolgus monkeys is quite favorable relative to the known
      effects of other phosphorothioate oligonucleotides, particularly with respect to
      the blood level-related toxicities of this class of compounds, including
      complement activation and inhibition of coagulation. This study found no
      toxicities that were expected to be clinically significant.

PMID- 11446592
TI  - Specific inhibition of the rat ligand-gated ion channel P2X3 function via
      methoxyethoxy-modified phosphorothioated antisense oligonucleotides.
AB  - P2X3 is one receptor of a family of seven ligand-gated ion channels responding to
      purines. Increasing evidence indicates its involvement in neuronal signaling and
      in pain. However, there is currently no selective inhibitor known for this
      subtype. In order to obtain such a specific inhibitor, a variety of antisense
      oligonucleotides (ASO) against rat P2X3 was tested, and dose-dependent, sequence
      specific downregulation of the rat P2X3 receptor (expressed in a Chinese hamster
      ovary cell line [CHO-K1]) on the mRNA, protein, and functional levels was
      observed. Using real-time quantitative PCR, a dose-dependent downregulation of
      P2X3 mRNA by ASO, as compared with untreated and mismatch controls, was
      demonstrated. Subsequently, downregulation by the two most potent ASO was
      confirmed at the protein level by Western blot. Sequence specificity was shown by
      titration of mismatches to the original selected oligonucleotide, and this
      correlated with progressive loss of P2X3 inhibition. The functional response of
      the P2X3 receptor was examined using whole-cell voltage clamping. Upon
      application of 10 microM of a nonspecific agonist, alpha,beta-methylene-ATP
      (alphabeta meATP), pretreatment with increasing amounts of the most active ASO
      5037 correlated with a decrease in depolarization. The ability to specifically
      downregulate the P2X3 receptor by ASO treatment will allow investigation of the
      biologic role of this receptor in neuronal tissues and eventually in in vivo
      models of chronic pain.

PMID- 11446593
TI  - Mitochondria transfection by oligonucleotides containing a signal peptide and
      vectorized by cationic liposomes.
AB  - The progress of research in gene therapy allows hope for treatment of
      mitochondrial genetic disorders provided that efficient methods for gene transfer
      into mitochondria can be found. In this work, we have used an oligonucleotide
      coupled covalently to a mitochondria-targeted peptide at one end and a cationic
      liposome prepared from trimethyl aminoethane carbamoyl cholesterol iodide (TMAEC
      Chol) to carry it in living cells. With a fluorescent probe to label the
      oligonucleotide at the other end and by means of confocal microscopy, we show
      that such modified oligonucleotides complexed to liposomes enter into the
      cytoplasm of human fibroblasts in primary culture, and then, after dissociation
      from the complexes, they penetrate into the mitochondria. The fluorescence was
      still observed after 8 days, suggesting the continued presence of
      oligonucleotides. At the concentrations used for this study, the cationic
      liposomes have practically no effect on cell growth, as revealed by the MTT
      assay.

PMID- 11446594
TI  - From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides
      containing CpG sequences from bacterial DNA.
AB  - Several types of immune cells possess pattern recognition receptors (PRR) that
      can distinguish prokaryotic DNA from vertebrate DNA by detecting unmethylated CpG
      dinucleotides in particular base contexts (CpG motifs). Bacterial DNA or
      synthetic oligodeoxynucleotides containing these CpG motifs activate both innate
      and acquired immune responses that have evolved to protect against intracellular
      infections. These T helper 1 (Th1)-like immune responses include activation of B
      cells, dendritic cells, macrophages, and natural killer (NK) cells. CpG DNA
      induced immune activation can protect against infection either alone or in
      combination with a vaccine and is effective in the immunotherapy of allergic
      diseases and cancer. Human clinical trials using such CpG DNA are currently
      underway.

PMID- 11446595
TI  - Aberrant conduction or ectopic beats?

PMID- 11446596
TI  - A man with a history of skin lesions and seizures.
AB  - A 38-year-old man presented with painful growths around his toenails. Since their
      first occurrence at age three, several had been surgically removed. He had had
      similar growths around his fingernails and multiple facial lesions since age
      seven.

PMID- 11446597
TI  - Case in point. Spontaneous pneumothorax with spontaneous resolution.

PMID- 11446598
TI  - Lyme disease: a clinical update.
AB  - With adequate attention to specifics and details, the diagnosis and management of
      Lyme disease are usually relatively straight-forward. Still, there can be
      subtleties--for instance, in determining precisely what pathogen a tick bite
      transmitted, whether a patient's arthralgia is truly Lyme arthritis, or whether
      "positive" serologies represent refractory Lyme disease.

PMID- 11446599
TI  - Case in point. Perineuroma.

PMID- 11446600
TI  - Practical management of acute diarrhea.
AB  - A careful history and physical examination are usually enough to assess illness
      severity, the need for further labortory tests, and often the cause. Supportive
      treatment generally suffices However, antibiotic or probiotic therapy should be
      considered in selected patients.

PMID- 11446601
TI  - Medicinal herbs: answers and advice, part 1.
AB  - Many herbal medicines have been used for centuries but have only recently been
      subjected to rigorous scientific scrutiny. Fever-few, milk thistle, tea tree oil,
      and valerian are considered safe for use by most patients. All four appear to
      provide some benefits in treating or preventing illness, but the supporting
      evidence is inconclusive in some cases.

PMID- 11446603
TI  - Clinical consultation: messages from complementary medicine.

PMID- 11446602
TI  - Back to irrational exuberance.

PMID- 11446604
TI  - Ethics and research beyond western society.

PMID- 11446605
TI  - The organ retention furore: the need for consent.

PMID- 11446606
TI  - Please mind the gap: addressing the divide between primary and secondary care.

PMID- 11446607
TI  - Depression in advanced cancer--a hidden symptom.

PMID- 11446608
TI  - Fever of unknown origin.

PMID- 11446609
TI  - Hospital acquired pneumonia.

PMID- 11446610
TI  - Psychological management following deliberate self-harm.

PMID- 11446611
TI  - Acute back pain.

PMID- 11446612
TI  - The management of atrial fibrillation.

PMID- 11446613
TI  - The challenge for medicine.
AB  - The biggest challenge for clinicians is their relationship with patients and the
      public. As knowledge and technical possibilities have advanced, there is evidence
      that the healthcare system is falling down in the more mundane aspects of
      healthcare. What has gone wrong with healthcare? Four published case studies are
      discussed. The government and the General Medical Council are determined to put
      the patient at the centre of healthcare. Examples of what this means are given
      from the NHS Plan, the Duties of a Doctor and recommendations from a Leeds Castle
      healthcare symposium. The changes involved are articulated from clinicians'
      perspectives and the patient perspective draws on recent publications documenting
      three (journalist) patients' experiences. Professionals will have to be trained
      more with the patient in mind. Allegiances will be to patients and teams rather
      than institutions and teams must be clearly accountable. We are ready.

PMID- 11446614
TI  - Ethical approval for health research in central and eastern Europe: an
      international survey.
AB  - Research ethics committees in central and eastern Europe are increasing in
      importance as institutions in this region host a growing and more diverse range
      and volume of health-related research, with funding from an increasingly wide
      variety of sources. AIM: To describe the arrangements for ethical supervision of
      research in eleven countries of central and eastern Europe, so as to identify
      examples of good practice and areas of weakness. METHODS: A questionnaire was
      sent to key informants known to be active in health-related research in Albania,
      Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Lithuania, Poland, Romania,
      Russia, and Ukraine in October 2000. It sought information on the composition and
      functioning of ethics committees, their training and any public concerns about
      the ethics of health-related research. RESULTS: All countries except Ukraine
      confirmed that decision-making committee structures operate to oversee the ethics
      of research on human subjects. In all countries except Albania committees are
      comprised of medical and non-medical members. Members received specific training
      in bioethics in Estonia, Hungary, and Lithuania. Countries had made different
      degrees of progress in implementing arrangements for coordinating multi-site
      research and for monitoring research once it had commenced. Public concern about
      ethical issues arising from health-related research was rare. CONCLUSION: The
      development of ethical supervision of health-related research in central and
      eastern Europe varies considerably. In some countries there are significant
      weaknesses that should be addressed. Other countries could serve as examples of
      good practice in the region. A major challenge is how the public can be involved
      in this process.

PMID- 11446615
TI  - European collaboration in research into rare diseases: experience of the European
      Neuromuscular Centre.
AB  - An understanding of the possible causes, prevention and treatment of rare, so
      called 'orphan disease' requires collaboration in research between different
      centres with the sharing of information. In the case of neuromuscular disorders
      (such as muscular dystrophies or hereditary neuropathies) this has been achieved
      through European collaborative research encouraged and facilitated by the
      European Neuromuscular Centre (ENMC). The successful example of ENMC provides a
      model for the investigation of other rare 'orphan' disorders or even rare
      problems occurring in common disorders.

PMID- 11446616
TI  - Rediscovering the wheel--teaching communication skills using video taped clinical
      consultations in specialist training.
AB  - Communication skills are inevitably used during the clinical consultation in
      medicine. Unlike trainees in general practice, trainees in specialist and general
      medicine are not formally trained in communications skills. We used methods for
      training communication skills developed in general practice and videoed
      consultations with simulated patients, adapted for neurology, and found these to
      be valued by our trainees. In specialist medicine we need to begin exploring how
      to help our trainees learn communication skills; perhaps our colleagues in
      general practice can show us where to start?

PMID- 11446617
TI  - Acute coronary syndromes.
AB  - Acute coronary syndromes have been subject to revisions of both definition and
      treatment in recent years. As a result, more patients with these conditions are
      seen by physicians and more are considered for varied forms of treatment. Much of
      the clinical decision making is based upon trials that have identified reductions
      in relative risk for the treated patients. This review discusses the
      pathophysiology of the condition as well as the therapeutic options (without
      issuing guidelines). There are considerable challenges for physicians managing
      patients with these conditions. These challenges are in the conventional areas of
      risk stratification and cost, but are also in the logistics of investigating and
      revascularising these patients as quickly as possible.

PMID- 11446618
TI  - Eosinophil trafficking in asthma.
AB  - Asthma is characterised by a 50-fold increase in the number of eosinophils
      relative to neutrophils in the bronchial mucosa. This is the result of the
      cumulative and sequential effects of several, approximately fourfold, increases
      in selective eosinophil versus neutrophil migration occurring at a number of
      stages in the life cycle of the eosinophil. These events, which are integrated
      and directed by allergen-specific T helper 2 lymphocytes through the generation
      of interleukin (IL)-5, IL-4 and IL-13, include: effects on the bone marrow,
      mediated principally by IL-5, which result in a fourfold increase in circulating
      eosinophils selective tethering of eosinophils to venular endothelium through the
      combined effects of P-selectin/P-selectin glycoprotein ligand (PSGL)-1 and very
      late activation antigen (VLA)-4/vascular cell adhesion molecule-1, which has the
      potential for an up to tenfold increase in eosinophil versus neutrophil adhesion
      selective chemotaxis under the influence of CC chemokines prolonged survival,
      again mediated by IL-5. The implications of this multistep process are that
      antagonists of IL-5, VLA-4, PSGL-1 and CC chemokine receptor 3, as well as IL-4
      and IL-13, each have the potential markedly to inhibit eosinophil recruitment in
      asthma.

PMID- 11446619
TI  - Non-curative chemotherapy for cancer--is it worth it?

PMID- 11446620
TI  - Why are you doctors? The importance of care and compassion.

PMID- 11446621
TI  - A study of storytelling, humour and learning in medicine.
AB  - Story telling is a fundamental part of clinical practice. It provides the
      mechanism by which doctors and patients communicate and understand the meaning of
      illness and possible ways of dealing with it. Humour is a particular aspect of
      story telling and, while there are some negative aspects, generally does have a
      therapeutic benefit. The physiological effects of laughter are considerable. Both
      story telling and humour are important for learning and are complementary to the
      more formal learning from text books and lectures. Stories assist in the
      development of emotional knowledge. The hypothesis of the contagious theory of
      behaviour change is presented as a way in which ideas are transmitted from one
      person to another.

PMID- 11446622
TI  - Diseases the doctor (or autoanalyser) says you have got.
AB  - Much of modern medical practice involves treating patients with asymptomatic
      conditions or risk factors which I call 'diseases the doctors says you've got'.
      These generally asymptomatic conditions, which are usually discovered by
      screening, include hypertension, hyperlipidaemia, many cases of type 2 diabetes
      and the post-menopausal state. My argument is that many doctors do not have the
      interest or inclination to follow such patients. However, persuading them to take
      their tablets or modify their diets or lifestyles is arguably more difficult than
      in the 'proper' diseases on which physicians spend most of their training. I
      suggest that the only way of doing this is to educate and enthuse the patients
      and find a way to make them as interesting as the cases of the rare diseases we
      all find so fascinating.

PMID- 11446623
TI  - The College of Physicians in the nineteenth century.
AB  - For much of the nineteenth century (during which there were 16 Presidents) events
      within the College were dominated by widespread demands for medical reform,
      culminating in the great Medical Reform Act of 1858. This led to major changes
      within the College, including an overhaul of the system(s) of elections; the old
      licentiates disappeared (to be replaced by the new licentiates), whilst
      introduction of the membership (by examination) was instituted. The style of
      Presidential elections was also changed. Internal College activities centred on
      the Library and on the London Pharmacopoeia. Early in the century, the College
      once again moved geographically, this time from the City to the West End of
      London. Regarding contemporary issues, including medical advances (notably
      introduction of the 'germ-theory' of disease causation) and important social
      changes (dominated by Poor Law reform), the College's input proved minimal.

PMID- 11446625
TI  - Medical treatment at the end of life.

PMID- 11446626
TI  - Aspirin against cancer.

PMID- 11446627
TI  - Temporary cardiac pacing and the physicians of tomorrow.

PMID- 11446628
TI  - Temporary cardiac pacing and the physicians of tomorrow.

PMID- 11446629
TI  - Paediatricians should be more interested in adult disease.

PMID- 11446630
TI  - Statin therapy.

PMID- 11446631
TI  - New and efficient routes to biomolecules substituted with
      cyclopentadienyltricarbonylrhenium and -technetium derivatives.
AB  - The small, compact, robust, and nonpolar units of [CpM(CO)3] (M = Re, Tc) coupled
      with biomolecules may be considered as bioorganometallic entities of potential
      interest in the field of medicinal chemistry. However, the short half-life of
      useful radionuclides (186Re t1/2 = 3.7 d, 188Re t1/2 = 16.8 h, 99mTc t1/2 = 6 h),
      the risks inherent in their use, and their cost have led chemists to search for
      novel synthetic strategies that allow the rapid introduction of the [CpM(CO)3]
      moiety as a late step in the course of synthesizing the target molecule. The
      present paper describes different strategies recently reported in the literature
      to tackle this problem.

PMID- 11446632
TI  - Pre-reactive complexes in mixtures of water vapour with halogens:
      characterisation of H2O...ClF and H2O...F2 by a combination of rotational
      spectroscopy and ab initio calculations.
AB  - Complexes H2O...ClF and H2O...F2 were detected by means of their ground-state
      rotational spectra in mixtures of water vapour with chlorine monofluoride and
      difluorine, respectively. A fast-mixing nozzle was used in conjunction with a
      pulsed-jet, Fourier-transform microwave spectrometer to preclude the vigorous
      chemical reaction that these dihalogen species undergo with water. The ground
      state spectra of seven isotopomers (H2 16O...35ClF, H2 16O...ClF, H2 18O...35ClF,
      D2 16O... 35ClF, D2 16O...37ClF, HDO...35ClF and HDO...37ClF) of the ClF complex
      and five isotopomers (H2O...F2, H2 18O...F2, D2O...F2, D2 18O...Fi and HDO...F2)
      of the F2 complex were analysed to yield rotational constants, quartic
      centrifugal distortion constants and nuclear hyperfine coupling constants. These
      spectroscopic constants were interpreted with the aid of simple models of the
      complexes to give effective geometries and intermolecular stretching force
      constants. Isotopic substitution showed that in each complex the H2O molecule
      acts as the electron donor and either CIF or F2 acts as the electron acceptor,
      with nuclei in the order H2O...ClF or H2O...F2. For H2O...ClF, the angle phi
      between the bisector of the HOH angle and the O...Cl internuclear line has the
      value 58.9(16)degrees, while the distance r(O...Cl)= 2.6081(23) A. The
      corresponding quantities for H2O...F2 are phi = 48.5(21)degrees and r(O...Fi) =
      2.7480(27) A, where Fi indicates the inner F atom. The potential energy V(phi) as
      a function of the angle phi was obtained from ab initio calculations at the aug
      cc-pVDZ/MP2 level of theory for each complex by carrying out geometry
      optimisations at fixed values of phi in the range +/-80degrees. The global
      minimum corresponded to a complex of Cs symmetry with a pyramidal configuration
      at O in each. The function V(phi) was of the double-minimum type in each case
      with equilibrium values phie = +/-55.8degrees and +/-40.5degrees for H2O...ClF
      and H2O...F2, respectively. The barrier at the planar C2v conformation was V0=
      174cm(-1) for H2O...ClF and 7cm(-1) for H2O...F2. For the latter complex, the
      zero-point energy level lies above the top of the barrier.

PMID- 11446633
TI  - Interaction between dioxoruthenium(VI) porphyrins and hydroxylamines:
      coordination of N-substituted hydroxylamine to ruthenium and X-ray crystal
      structures of ruthenium complexes with a unidentate nitrosoarene ligand.
AB  - The interactions between dioxoruthenium(VI) porphyrins 1 with N
      phenylhydroxylamine or unsubstituted hydroxylamine are described. Reaction of
      complexes 1 with excess PhNHOH leads to isolation of
      bis(nitrosobenzene)ruthenium(II) porphyrins 3 and
      mono(nitrosobenzene)ruthenium(II) porphyrins 4. Both the types of ruthenium
      complexes are characterized by 1H NMR, IR, and UV/Vis spectroscopy, and mass
      spectrometry. The X-ray structure determinations on [Ru(II)(TPP)(PhNO)2] (3a),
      [Ru(II)(2,6-Cl-TPP)(PhNO)2] (3e), and [Ru(II)(4-MeO-TPP)(PhNO)(PhNH2)] (4d) (TPP
      tetraarylporphyrin) disclose a unidentate nitrosoarene coordination in all these
      complexes, with Ru-N(PhNO) bond lengths of 2.003(3) (3a, average), 1.991(3) (3e,
      average), and 2.042(2) A (4d). In the case of 4d, the Ru-N(PhNH2) bond length is
      found to be 2.075(3) A. Mechanistic investigations reveal the formation of
      intermediates [Ru(II)(Por)(PhNO)(PhNHOH)] (5; Por=porphyrin), a ruthenium complex
      with N-substituted hydroxylamine ligand, in the "1 + PhNHOH" system. The Ru
      NH(OH)Ph moiety in 5 undergoes no rapid exchange with free PhNHOH in solution at
      room temperature, as revealed by 1H NMR spectroscopy. Unlike the interaction
      between complexes 1 and PhNHOH, reaction of such complexes with NH2OH affords
      nitrosylruthenium(II) porphyrins [Ru(II)(Por)(NO)(OH)] (6).

PMID- 11446634
TI  - Preparation of resin-bound N-(alpha-methoxyalkyl)amides: an advantageous use of
      solid-phase chemistry for the handling of unstable precursors of the versatile N
      acyliminium ions.
AB  - The development of a new and efficient synthesis of resin-bound N-(alpha
      methoxyalkyl)amides is described. The condensation of aldehydes on a supported
      amide in the presence of trimethyl orthoformate afforded, in acidic media, the
      resin-bound N-acyliminium ion precursors. Repeating the reaction a second time
      led to a great improvement in yields, demonstrating one advantage of the solid
      phase chemistry for the handling of sensitive intermediates difficult to isolate.

PMID- 11446635
TI  - Synthesis of 5-azacastanospermine, a conformationally restricted azafagomine
      analogue.
AB  - The 5-aza-6-deoxy analogue of castanospermine (+/-)-5a and its 1-epimer (+/-)-5b
      was synthesized. The synthesis started from the known compound 5-benzyloxy-7
      hydroxyhepta-1,3-diene, which was protected and subjected to Diels-Alder reaction
      with 4-phenyl-1,2,4-triazoline-3,5-dione to give two epimeric adducts. One of
      these was transformed through epoxidation, acetolysis, a series of side-chain
      transformations that converted it into a terminally protected aldehyde,
      deprotection, and hydrogenolysis/reductive amination into 5a. By a similar set of
      reactions the other adduct epimer was converted into 5b. The castanospermine
      analogue 5a was a weaker inhibitor of almond beta-glucosidase and rice alpha
      glucosidase than castanospermine (2) or 1-azafagomine (4), but was considerably
      more potent than its epimer 5b. This suggests that these enzymes have a strong
      preference for binding substrates or azasugars with the 6-OH in an axial
      conformation.

PMID- 11446636
TI  - An efficient method for the preparation of 1'alpha-branched-chain sugar
      pyrimidine ribonucleosides from uridine: the first conversion of a natural
      nucleoside into 1'-substituted ribonucleosides.
AB  - The 1'alpha-phenylselenouridine derivative 13 was successfully synthesized by
      enolization of the 3',5'-O-TIPDS-2'-ketouridine 8, and was subjected to a radical
      reaction with a vinylsilyl tether--an efficient procedure for preparing 1'alpha
      branched-chain sugar pyrimidine nucleosides. Successive treatment of 8 with
      LiHMDS and PhSeCl in THF at < -70 degrees C gave the desired 1'-phenylseleno
      products in 85% yield as an anomeric mixture of the 1'alpha-product 11 and the
      1'beta-product 12 (11/12= 2.5:1). Highly stereoselective reduction at the 2'
      carbonyl of the 1'alpha-product 11 occurred from the beta-face by using
      NaBH4/CeCl3 in MeOH, and subsequent introduction of a dimethylvinylsilyl tether
      at the 2'-hydroxyl gave the radical reaction substrate 14. The photochemical
      radical atom-transfer reaction of 14 by using a high-pressure mercury lamp
      proceeded effectively in benzene to give the exo-cyclized PhSe-transferred
      product 18, in which (PhSe)2 proved to be essential as an additive for radical
      atom-transfer cyclization reactions. Subsequent phenylseleno-group elimination of
      18 gave the sugar-protected 1'alpha-vinyluridine. With this procedure, 1'alpha
      vinyluridine (22) and -cytidine (25), designed to be potential antitumor agents,
      were successfully synthesized. This study is the first example of
      functionalization at the anomeric 1'-position of a nucleoside by starting from a
      natural nucleoside to produce a ribo-type 1'-modified nucleoside.

PMID- 11446637
TI  - Intramolecular C-H activation by alkylpalladium(II) complexes: insights into the
      mechanism of the palladium-catalyzed arylation reaction.
AB  - The cyclization of [ArOCH2PdL2Cl] complexes proceeds at room temperature in CH3CN
      in the presence of base, such as KOPh or carbonate, to form palladacycles. The
      effect of substituents on the aryl moiety (p-MeO > H >p-NO2) is as expected for
      an electrophilic aromatic substitution by electrophilic Pd(II). The absence of
      isotopic effect is also consistent with this proposal. Cyclopalladation proceeds
      with bidentate ligands (dppf, COD and phen); although the C-H activation
      reactions are slower in these cases. The starting [ArOCH2Pd(PPh3)2Cl] and
      [ArOCH2Pd(PPh3)Cl]2 complexes were prepared by transmetalation of organostannanes
      [(ArOCH2)4Sn] with [Pd(PPh3)2Cl2] or [Pd(PPh3)Cl2]2, respectively. Cleavage of
      palladacycles with HCl also gave [ArOCH2PdL2Cl] complexes.

PMID- 11446638
TI  - New cyclohexadienone derivatives: preparation and chiral discrimination in high
      pressure Diels-Alder cycloadditions.
AB  - A wide range of cyclohexadienones has been synthesised in order to study their
      reactivity and their regio- and stereoselectivity with the enantiopure diene 1
      under high-pressure conditions. Computational investigations were used to point
      out some parameters which affect the reactivity in this high chiral
      discrimination process. In addition, the resulting [4+2] cycloadducts allowed the
      preparation of new polyfunctional cyclohexenone derivatives.

PMID- 11446639
TI  - Formation of cyclopentadienyl and ruthenacyclopentadienyl derivatives through
      ynenyl-diyne and ynenyl-alkyne couplings onto a triruthenium cluster core.
AB  - The compound [Ru3(mu-H)(mu3-eta2-ampy)(CO)9] (1; Hampy =2-amino-6-methylpyridine)
      reacts with diynes RC4R in THF at reflux temperature to give the ynenyl
      derivatives [Ru3(mu3-eta2-ampy)(mu-eta3-RC...CC-CHR)(mu-CO)2-(CO)6] (2: R=CH2OPh;
      3: R=Ph). These products contain a 1,4-disubstituted butynen-3-yl ligand attached
      to two ruthenium atoms. The compound [Ru3(mu-eta2-ampy)[mu3-eta6-PhCC5(C...CPh)
      HPh2](CO)7] (4), which contains an eta5-cyclopentadienyl ring and a bridging
      carbene fragment, has also been obtained from the reaction of 1 with
      diphenylbutadiyne. This compound arises from a remarkable [3+2] cycloaddition
      reaction of a preformed 1,4-diphenylbutynen-4-yl ligand with a triple bond of a
      second diphenylbutadiyne molecule. The reactivity of the ynenyl derivatives 2 and
      3 with diynes and alkynes has been studied. In all cases, compounds of the
      general formula [Ru3(mu-eta2-ampy)[mu3-eta5-C(=CHR)C=CRCR1=CR2](CO)7] (5-17) have
      been obtained. They all contain a ruthenacyclopentadienyl fragment formed by
      coupling of the coordinated ynenyl ligand of 2 (R = CH2OPh) or 3 (R = Ph) with a
      triple bond of the new reagent (the CR1=CR2 fragment results from the incoming
      diyne or alkyne reagent). While most of the products derived from 2 have the
      alkenyl C=CHR fragment with a Z configuration (R cis to Ru), all the compounds
      obtained from 3 have this fragment with an E configuration. Except 2 and 3, all
      the cluster complexes described in this article have a five-electron donor ampy
      ligand attached to only two metal atoms, a coordination mode unprecedented in
      cluster chemistry.

PMID- 11446640
TI  - A highly efficient synthetic strategy for polymeric support synthesis of Le(x),
      Le(y), and H-type 2 oligosaccharides.
AB  - The O-protecting groups Levulinoyl (Lev) and 9-fluroenylmethoxycarbonyl (Fmoc)
      offer an attractive set of orthogonal protecting groups which are compatible with
      base sensitive N-trichloroethoxylcarbonyl (Troc) group. B exploiting these
      orthogonal protecting groups and a novel phenolic ester linker, a series of
      oligosaccharide of biological importance, Le(x), H-type 2, and Le(y), were
      synthesized on the polytheylene glycol resin MPEG (Mw 5000). The products bearing
      a p-hydroxybenzyl group could be easily converted into glycosyl donors for
      further synthesis. Using this strategy, a spacer containing tumor antigen Le(y)
      Lac hexasaccharide was described. The artificial spacer at the reducing end
      provides an opportunity for selective conjugation to an appropriate carrier
      protein for immunlogical studies.

PMID- 11446641
TI  - Heterologous over-expression of alpha-1,6-fucosyltransferase from Rhizobium sp.:
      application to the synthesis of the trisaccharide beta-D-GlcNAc(1-->4)-[alpha-L
      Fuc-(1-->6)]-D-GLcNAc, study of the acceptor specificity and evaluation of
      polyhydroxylated indolizidines as inhibitors.
AB  - An efficient heterologous expression system for overproduction of the enzyme
      alpha-1,6-Fucosyltransferase (alpha-1,6-FucT) from Rhizobium sp. has been
      developed. The gene codifying for the alpha-1,6-FucT was amplified by PCR using
      specific primers. After purification, the gene was cloned in the plasmid pKK223
      3. The resulting plasmid, pKK1,6FucT, was transformed into the E. coli strain XL1
      Blue MRF'. The protein was expressed both as inclusion bodies and in soluble
      form. Changing the induction time a five-fold increase of enzyme expressed in
      soluble form was obtained. In this way five units of enzyme alpha-1,6-FucT can be
      obtained per liter of culture. A crude preparation of the recombinant enzyme was
      used for the synthesis of the branched trisaccharide alpha-D-GlcNAc-(1-->4)
      [alpha-L-Fuc-(1-->6)]-D-GlcNAc (3), from chitobiose (2) and GDP-Fucose (1). After
      purification, the trisaccharide 3 was obtained in a 84% overall yield. In order
      to elucidate the structural requirements for the acceptors, the specificity of
      the enzyme was studied towards mono-, di- and trisaccharides, which are
      structurally related to chitobiose. The enzyme uses, among others, the
      disaccharide N-acetyl lactosamine as a good substrate; the monosaccharide GlcNAc
      is a weak acceptor. Finally, several racemic polyhydroxylated indolizidines have
      been tested as potential inhibitors of the enzyme. Indolizidine 21 was the best
      inhibitor with an IC50 of 4.5 x 10(-5) M. Interestingly, this compound turned out
      to be the best mimic for the structural features of the fucose moiety in the
      presumed transition state.

PMID- 11446642
TI  - Effects of dimerization on protein electron transfer.
AB  - In order to investigate the relationship between the rate of protein-protein
      electron transfer and the structure of the association complex, a dimer of the
      blue copper protein azurin was constructed and its electron exchange properties
      were determined. For this purpose, a site for covalent cross-linking was
      engineered by replacing the surface-exposed asparagine 42 with a cysteine. This
      mutation enabled the formation of disulfide-linked homo-dimers of azurin. Based
      on NMR line-broadening experiments, the electron self-exchange (e.s.e.) rate
      constant for this dimer was determined to be 4.2(+/-0.7) x 10(5)M(-1)s(-1), which
      is a seven-fold decrease relative to wild-type azurin. This difference is
      ascribed to a less accessible hydrophobic patch in the dimer. To discriminate
      between intramolecular electron transfer within a dimer and intermolecular
      electron transfer between two dimers, the e.s.e. rate constant of (Cu-Cu)-N42C
      dimers was compared with that of (Zn-Cu)- and (Ag-Cu)-N42C dimers. As Zn and Ag
      are redox inactive, the intramolecular electron transfer reaction in these latter
      dimers can be eliminated. The e.s.e. rate constants of the three dimers are the
      same and an upper limit for the intramolecular electron transfer rate of 10 s(-1)
      could be determined. This rate is compatible with a Cu-Cu distance of 18 A or
      more, which is larger than the Cu - Cu distance of 15 A observed in the wild-type
      crystal structure that shows two monomers that face each other with opposing
      hydrophobic patches. Modelling of the dimer shows that the Cu-Cu distance should
      be in the range of 17 A < rCu-Cu < 28 A, which is in agreement with the
      experimental findings. For efficient electron transfer, it appears crucial that
      the two molecules interact in the proper orientation. Direct cross-linking may
      disturb the formation of such an optimal electron transfer complex.

PMID- 11446643
TI  - Expanded phthalocyanine analogues: synthesis and characterization of new triazole
      derived annulenes containing six heterocyclic subunits.
AB  - A series of heteroannulenes 3a-f containing four subunits of isoindole, two 1,2,4
      triazole moieties, and six aza bridges have been synthesized by dimerization of
      the corresponding metallated, three-unit intermediates 5a-f. All these 28 pi
      electron triazolephthalocyanine derivatives coordinate two metal ions within
      their central cavity and are the first examples of expanded
      heterophthalocyanines. Spectroscopic properties of these macrocycles show
      evidence for extended conjugation and antiaromaticity. The nature of the metal
      ions plays a definite role in the electronic properties of these derivatives.

PMID- 11446644
TI  - Supramolecular organometallic polymer chemistry: multiple morphologies and
      superstructures from the solution self-assembly of polyferrocene-block
      polysiloxane-block-polyferrocene triblock copolymers.
AB  - The solution self-assembly of an organometallic-inorganic triblock copolymer,
      poly(ferrocenyldimethylsilane)-block-poly(dimethylsiloxane)-block-poly
      (ferrocenyldimethylsilane) (PFDMS-b-PDMS-b-PFDMS, 3b; block ratio 1:13:1; Mn =
      2.88 x 10(4) gmol(-1), polydispersity (PDI) 1.43 (gel permeation chromatography,
      GPC)) was studied in n-hexane, a PDMS block selective solvent. Transmission
      electron microscopy (TEM), atomic force microscopy (AFM), and TEM with negative
      staining analysis of these micellar solutions after solvent evaporation revealed
      the presence of multiple micellar morphologies including spheres, cylinders, and
      novel flower-like supramolecular aggregates. TEM analysis of samples fractionated
      by ultracentrifugation and preparative size-exclusion chromatography suggest that
      the formation of multiple morphologies is a consequence of compositional
      variations. When micellar solutions were prepared at 50 degrees C (above the
      glass transition of the PFDMS core-forming block) flower-like micellar aggregates
      similar to those present in micellar solutions prepared at room temperature also
      formed. However, after solvent evaporation, TEM analysis of micellar solutions
      prepared in decane at about 150 degrees C, above the melt temperature of the
      PFDMS core (ca. 120-145 degrees C), revealed the presence of spherical micelles
      (when decane solutions at 150 degrees C were rapidly cooled to room temperature)
      and rod-like cylindrical micelles (when decane solutions at 150 degrees C were
      slowly cooled to room temperature). In contrast,
      poly(ferrocenylmethylethylsilane)block-poly(dimethylsiloxane)-block
      poly(ferrocenylmethylethylsilane) (PFMES-b-PDMS-b-PFMES, 4; block ratio 1:16:1;
      Mn=2.90x10(4)g mol(-1), PDI= 1.42 (GPC)) and poly(ferrocenylmethylphenylsilane)
      block-poly(dimethylsiloxane)-block-poly(ferrocenylmethylphenylsilane) (PFMPS-b
      PDMS-b-PFMPS, 5; block ratio 1:15:1; Mn=3.00 x 10(4) gmol(-1), PDI = 1.38 (GPC)),
      which possess completely amorphous organometallic core-forming blocks, formed
      only spherical micelles in hexane at room temperature. These observations
      indicate that crystallinity of the insoluble polyferrocenylsilane block is a
      critical factor in the formation of the nonspherical micelle morphologies.

PMID- 11446645
TI  - Metallocyclic receptors with Re(I)/Os(II)-based moieties: molecular photophysics
      and selective molecular sensing.
AB  - New metallocyclic Re(I) and Os(II) complexes with polyphosphane/polyyne spacers,
      including dimers [(Re(CO)3Cl(C2nP2))2] (n = 1, 1; 2, 2) and tetramers
      [(Re(CO)3Cl(C2nP2))4] (n = 1, 3; 2, 4, C2P2 = Ph2P-C...C-PPh2, C4P2 = Ph2P-C...C
      C...C-PPh2), as well as the mixed-metal [(Re(CO)3Cl)2(Os(bpy)2)2(C2P2)4](PF6)4
      (6, bpy = 2,2'-bipyridine) and its precursor [Os(bpy)2(C2P2)2](PF6)2 (5) have
      been synthesized. Characterization has been carried out using 31P(1H) NMR,
      FAB/MS, ESI/MS, IR spectroscopy, elemental analysis (EA), and X-ray single
      crystal structure determination. These new metallocyclic complexes are found to
      be emissive, with a characteristic ReI-based emission at 505-525 nm (lifetimes of
      3.4-6.8 ns) and an Os(II)-based emission at 600-605 nm (lifetimes of 650-675 ns).
      High quantum yields of 0.25 and 0.17 were observed for 5 and 6, which were
      representative of the few most emissive species reported with Os(II) centers.
      Efficient energy transfer from the Re(I) donor to the Os(II) acceptor was also
      found. In addition, a host-guest study was performed using emissive metallocycle
      6, and host-guest binding constants of 775M(-1), 1580M(-1), and 1680M(-1) were
      obtained for the guests anisole, 1,4-dimethoxybenzene, and 1,3,5
      trimethoxybenzene, respectively. The correlation between the guest molecule size,
      cavity dimension, and the host-guest binding constant is discussed. Furthermore,
      the relationship between the pi-acceptor ability of the nonchromophoric
      phosphanes, the energy gap between the ground and excited state, and the
      nonradiative decay rate constant (knr) is also explored.

PMID- 11446646
TI  - Endo-selective intramolecular Pauson-Khand reactions of gamma-oxygenated
      alpha,beta-unsaturated phenylsulfones.
AB  - A wide variety of 1,6-enynes and 1,7-enynes incorporating gamma-oxygenated
      alpha,beta-unsaturated phenylsulfone moieties have readily been prepared by
      piperidine-promoted condensation of the corresponding alkynyl aldehyde with
      phenylsulfonyl-(p-tolylsulfinyl)methane and further protection of the hydroxyl
      group. Despite the enduring claim concerning the unsuitability of electronically
      deficient olefins in Pauson-Khand reactions, we report that these 1-sulfonylated
      enynes are excellent substrates in intramolecular Pauson-Khand reactions under
      both thermal and amine N-oxide-promoted conditions. Moreover, in contrast with
      the usual exo-selective Pauson-Khand cyclization of allylic substituted enynes,
      the reactions of these 1-sulfonylated-3-oxygenated enynes occur with a moderate
      or high endo selectivity. The evaluation of the chemical and stereochemical scope
      of the process in comparison with the Pauson-Khand cyclization of non
      sulfonylated enynes, its application to the stereoselective preparation of
      optically pure C6-substituted bicyclo[3.3.0]oct-1-en-3-ones, and the
      interpretation of the stereochemical outcome are also discussed.

PMID- 11446647
TI  - Multipeptide-metalloporphyrin assembly on a dendrimer template and photoinduced
      electron transfer based on the dendrimer structure.
AB  - To construct an artificial photosynthetic system, peptide dendrimers [n-(X
      HLY)PAMAMs: X = R, E; Y= L, F; n=4, 8, 16, 32 and 64 segments], in which
      amphiphilic alpha-helix peptides (X-HLY: R-HLL, E-HLL and R-HLF) were introduced
      at the end groups of polyamidoamine dendrimers (PAMAMs), were designed and
      synthesized. The peptide dendrimers 64-(X-HLY)PAMAMs are novel synthetic
      biopolymers with an enormous molecular weight, about 160 kDa, and with a
      regulated amino acid sequence and three-dimensional conformation. The peptide
      dendrimers bound Fe(III)- or Zn(II)-mesoporphyrin IX per two alpha-helices; this
      afforded a multimetalloporphyrin assembly similar to the natural light-harvesting
      antennae in photosynthetic bacteria. Circular dichroism studies and peroxidase
      activity measurements revealed that metalloporphyrins were coordinated to the
      peptide dendrimers in a regulated manner and packed more densely with the growth
      of the dendrimer generation. Fluorescence quenching and photoreduction studies
      with methylviologen demonstrated that the photoinduced electron-transfer function
      with the peptide dendrimer-multi-Zn-MP was accomplished more effectively as the
      dendrimer generation increased. Thus, the three-dimensional assembly of
      metalloporphyrins and peptides in the dendrimer was an effective module for light
      harvesting antennae in an artificial photosynthetic system.

PMID- 11446648
TI  - Synthesis and separation of structural isomers of 2(3),9(10),16(17),23(24)
      tetrasubstituted phthalocyanines.
AB  - The 2(3),9(10),16(17),23(24)-tetrasubstituted metalphthalocyanines 1-7 (M = In,
      Ni, Zn) were synthesized, as mixtures of four different structural isomers, from
      the corresponding 4-alkoxy-1,2-dicyanobenzenes and the appropriate metal salts.
      Separation of the four structural isomers was successfully achieved on a C30
      alkyl phase by high-performance liquid chromatography (HPLC). The determination
      of the point groups of the structural isomers was carried out for 1 and 3, the
      composition of the structural isomers of 4-7 was accomplished by comparing their
      retention times and UV/Vis spectra with the data of 1 and 3. For the
      phthalocyanines 8-10 and the naphthalocyanines 11 and 12 only the C4h and D2h
      isomers could be separated.

PMID- 11446649
TI  - Towards a better understanding of the magnetic interactions within m-phenylene
      alpha-nitronyl imino nitroxide based biradicals.
AB  - An extensive investigation of the magnetic properties of three series of
      biradicals (bis-nitronyl nitroxides diNN-R, bis-imino nitroxides diIN-R and mixed
      INNN-R, where R is either hydrogen, a triple bond or trimethylsilylacetylenic
      group) has been carried out to give clear values of the intramolecular
      interactions through the m-phenylene coupling unit with alpha-nitronyl nitroxides
      (NN) or alpha-imino nitroxides (IN). An EPR study of the molecules in the
      isolated state is validated by ab initio calculations, which show the respective
      influence of spin polarisation and molecular conformation on the singlet-triplet
      gaps. All these results indicate that the triplet state is the ground state for
      such biradicals, except when the imidazolyl cycles are orthogonal to the phenyl
      ring. The magnetic properties of the biradicals in the solid state can be
      rationalised by examination of the short contacts produced between the ONCNO and
      ONCN groups. EPR studies on single crystals of the H-substituted series have
      confirmed the presence of a structural distortion for diNN-H whereas diIN-H and
      INNN-H do not exhibit such a peculiarity. The magnetic behaviour of diIN-H is
      described well by a four-spins model, with a strong intermolecular
      antiferromagnetic interaction of -90 K, whereas in the case of the two other
      compounds, a supplementary contact involves more complex interactions between the
      dimers. The compound diNN-tmsa exhibits a ferromagnetic intermolecular
      interaction of +11 K within the dimers, and this could be attributed to the
      relative disposition of the imidazolyl rings. Compound diNN-tr reveals a chain
      like behaviour, whereas diIN-tr shows a predominant antiferromagnetic interaction
      within the dimers. The values for the intramolecular interactions in the solid
      state are in good agreement with those found for the isolated molecules.

PMID- 11446650
TI  - The Pd-catalyzed coupling of allyl halides and tin aryls: why the catalytic
      reaction works and the stoichiometric reaction does not.
AB  - Arylallylpalladium complexes [Pd(5-C6F5-eta3-cyclohexenyl)(C6Cl2F3)(NCMe)] (10)
      and [Pd2(mu-C6Cl2F3)2(5-C6F5-1,3-eta3-cyclohexenyl)2] (13) have been synthesized.
      Complex 13 is an example of a rare class of metal complexes with aryl bridges and
      its X-ray crystal diffraction structure has been determined. These
      arylallylpalladium complexes are involved in the coupling of Bu3SnRf (1, Rf =
      dichlorotrifluorophenyl) and [Pd2(mu-Br)2(5-C6F5-1,3-eta3-cyclohexenyl)2] (2);
      complex 10 has been detected in the course of the stoichiometric coupling
      reaction in acetonitrile. Decomposition experiments of 10 and 13 in different
      conditions, and comparison with the reactions of 1 and 2, allow us to determine
      that reductive elimination does not occur in the absence of additives. p
      Benzoquinone coordinates to Pd to give complex 15 and promotes reductive
      elimination to give the coupling products selectively. The outcome of the
      coupling reaction is controlled by the reductive elimination step, but the
      overall rate is controlled by the faster preequilibrium, which determines the
      concentration of 10 or 13. Palladium-catalyzed coupling of allyl halides and tin
      aryls works better than the stoichiometric allyl-aryl reductive coupling on
      isolated allylarylpalladium complexes, because they benefit from the presence in
      the solution of substrate allylic halides acting as electron-withdrawing olefins
      and promoting reductive elimination. More efficient allyl-aryl couplings, whether
      stoichiometric or catalytic, can be achieved upon addition of p-benzoquinone to
      the reaction mixture in a noncoordinating solvent.

PMID- 11446651
TI  - Hemolytic-uremic syndrome and complement factor H deficiency: clinical aspects.
AB  - A subgroup of patients with hemolytic-uremic syndrome (HUS) has emerged with
      complement factor H deficiency. These have come to light because of persistent
      hypocomplementemia, although the molecular finding by Warwicker et al in one
      pedigree suggests that not all cases exhibit systemic hypocomplementemia. These
      patients have an atypical presentation in that they do not consistently have a
      prodrome of enterocolitis although precipitating factors may include infections
      of various kinds. Patients usually have severe hypertension early in the course
      of their illness, tend to relapse, and have a poor prognosis. The age of onset
      varies from neonates to adults. Plasma exchange and replacement with a plasma
      product containing factor H seem a reasonable option in the absence of better
      evidence. Kidney transplantation can meet with recurrence of HUS, but the risk of
      grafting has yet to be established, and a strategy to overcome graft recurrence
      is needed. Because of the great rarity of this disorder, a strong case can be
      made for international registries of atypical HUS cases so that clinical and
      laboratory investigation is promoted.

PMID- 11446652
TI  - Complement factor H: physiology and pathophysiology.
AB  - The human plasma protein factor H, which is a multifunctional, multidomain
      protein, acts as a central regulator of the complement system. In addition to its
      complement regulatory activities, factor H has multiple physiological activities
      and 1) acts as an extracellular matrix component, 2) binds to cellular receptors
      of the integrin type, and 3) interacts with a wide selection of ligands, such as
      the C-reactive protein, thrombospondin, bone sialoprotein, osteopontin, and
      heparin. Recent genetic reports, which show involvement of factor H in the human
      disease hemolytic-uremic syndrome (HUS), have attracted the attention of both
      clinicians and basic complement researchers to the role of factor H in the
      pathophysiology of HUS.

PMID- 11446653
TI  - The role of coagulation and fibrinolysis in the pathogenesis of diarrhea
      associated hemolytic uremic syndrome.
AB  - The hemolytic-uremic syndrome (HUS) is a frequent cause of acute renal failure in
      childhood. It comprises acute acquired hemolysis, thrombocytopenia, and renal
      dysfunction. Very many disease processes can lead to this constellation, the most
      frequent one in childhood being an infection by bacteria that produce Shiga toxin
      or Shiga-like toxins (SLTs). In industrialized countries, the first identified
      human pathogen to cause HUS was Escherichia coli O157H7, and this organism
      remains the most common one. The mechanisms by which these bacteria cause
      hemorrhagic colitis and HUS are incompletely understood. The bacteria are able to
      adhere to the mucosa of the colon. The local and systemic effects that follow the
      intestinal invasion are responsible for the bloody diarrhea. In a further step,
      the SLTs reach the blood stream and attach to the endothelium of the small
      arterioles mainly in the kidney but also in other organs. The endothelial cells
      express a toxin-specific receptor that enables the contact between toxin and
      cells. Damage to the endothelium causes platelet aggregation and activation,
      which trigger fibrin deposition. Although thrombotic changes in the
      microcirculation have been recognized in many histological studies, it is only
      recently that coagulation studies have been able to demonstrate clearly localized
      intravascular coagulation. The finding that the fibrinolytic system is inhibited
      in HUS has been challenged. By using specific and sensitive tests to measure the
      active moiety of plasminogen activator inhibitor type 1 (PAI-1) and comparing the
      findings in HUS patients and appropriate controls, it has become clear that in
      diarrhea-associated HUS the fibrinolytic system is rather stimulated. In this
      contribution the pathophysiology of diarrhea-associated HUS is discussed with
      special emphasis on coagulation and fibrinolysis.

PMID- 11446654
TI  - The role of virulence factors in enterohemorrhagic Escherichia coli (EHEC)-
      associated hemolytic-uremic syndrome.
AB  - Enterohemorrhagic Escherichia coli (EHEC) are the most common cause of
      postdiarrheal hemolytic-uremic syndrome (HUS). The most important EHEC serotype
      implicated worldwide is O157:H7. However, several so-called non-O157 EHEC
      serotypes have emerged. After a mean incubation period of 3 days, patients
      develop watery diarrhea accompanied by cramping abdominal pain. During the next
      days, in most patients watery diarrhea changes to bloody diarrhea. One week after
      the onset of diarrhea, in about 15% of infected patients under 10 years of age
      EHEC infection results in a systemic complication, HUS. Shiga toxins (Stxs) are
      considered the major virulence factors of EHEC involved in the pathogenesis of
      HUS. It is generally believed that after intestinal infection with EHEC, Stxs
      cross the intestinal barrier and bind to endothelial cells. At this point they
      presumably injure the host cell by inhibition of protein synthesis, stimulation
      of prothrombotic messages, or induction of apoptosis. The B subunit of Stx binds
      to the membrane receptor globotriaosylceramide (Gb3). Gb3 facilitates the
      endocytosis and intracellular trafficking of the toxin. The Stx A subunit
      hydrolyzes a specific adenine residue of the 60S ribosomal subunit of mammalian
      cells. As a consequence, Stx shuts down the protein machinery of the susceptible
      cell. The HUS is the net effect of a variety of interacting factors, including
      background risk of acquisition, host factors (such as age), virulence
      characteristics of the infecting EHEC strain, and exogenous factors. All known
      EHEC virulence determinants are located on mobile genetic elements, and this has
      an important impact on the evolution of these pathogens. The evolution of EHEC
      has a dynamic component that includes different genetic mechanisms. The recent
      progress in understanding the pathogenesis and epidemiology of EHEC infections
      forms a basis for the development of future strategies to prevent EHEC infections
      in humans.

PMID- 11446655
TI  - Thrombopoietin in thrombocytopenias of childhood.
AB  - This review summarizes the biology of thrombopoietin (TPO) in childhood. Studies
      on TPO and its receptor (c-mpl) have improved the understanding of inherited and
      acquired thrombocytopenias in childhood. Data are presented in this review
      regarding the molecular biology of TPO, differences in cellular effects on
      megakaryopoiesis, the regulation of TPO production, and TPO concentrations in
      health and disease. For neonatal thrombocytopenia, the focus is on early-onset
      thrombocytopenia associated with maternal diabetes, pregnancy-induced
      hypertension, intrauterine growth retardation, hypoxia, and sepsis. Fetal
      alloimmune thrombocytopenia allows insight into the biology of TPO when fetal
      megakaryopoiesis is chronically stimulated. In the thrombocytopenia absent radii
      syndrome and congenital amegakaryocytic thrombocytopenia, thrombocytopenia is
      caused by a disorder in the signal transduction at the c-mpl level and
      respectively directly on c-mpl. TPO concentrations in other inherited
      thrombocytopenias such as Fanconi anemia, Shwachman syndrome, Wiskott-Aldrich
      syndrome, and Bernard-Soulier syndrome are discussed. For acquired
      thrombocytopenias, data on TPO in aplastic anemia, immune thrombocytopenia, human
      immunodeficiency virus infection, and liver disease are given. Possible
      indications for a treatment with recombinant TPO in childhood are discussed, but
      the criteria to identify patients who would benefit need detailed evaluation.

PMID- 11446656
TI  - Possibilities and limitations of automated platelet counting procedures in the
      thrombocytopenic range.
AB  - The clinical decision to proceed with prophylactic platelet transfusions is
      widely based on trigger points for platelet counts being equal to 20, 10, or even
      5 x 10(9)/L. But an increasing number of publications show evidence that the
      conventional automated platelet counting methods are unable to provide
      consistently accurate results in this lower thrombocytopenic range. These
      measurement errors are mainly associated with the most commonly used impedance
      principle; optical methods seem to be more precise. The problems of counting
      imprecision in the low thrombocytopenic range can be avoided with direct or
      indirect immunological counting methods using monoclonal antibodies or by time
      consuming manual procedures. But how should new counting procedures be evaluated?
      Which method should be used as the "gold standard" for platelet counting? A way
      out of this apparent dilemma is the application of a statistical procedure as
      proposed by Gautschi et al. This mathematical model allows a reference method
      independent evaluation of new methods by calculation of the limits of detection
      (LD) and limits of quantification (LQ) based on the imprecision profile of the
      investigated method. Using this evaluation procedure, it can be shown that
      immunological automated counting methods can provide reliable, sufficient, and
      prompt platelet counts, especially in the thrombocytopenic range.

PMID- 11446657
TI  - Problems with platelet counting in thrombocytopenia. A rapid manual method to
      measure low platelet counts.
AB  - Because most automated platelet counters cannot be relied on in thrombocytopenia,
      clinicians face a problem when decision making is based on platelet counts.
      Therefore we evaluated a visual platelet counting method from a blood smear with
      white blood cells (WBCs) as reference (PCW = platelet count based on WBC).
      Platelet counting for 74 thrombocytopenic (<120 x 10(9)/L) children was performed
      with PCW and with an automated counter (impedance principle); both methods were
      compared with evaluation by phase-contrast microscopy as the standard method. The
      PCW correlated well with the phase-contrast microscopy evaluation (y = -0.38 +
      1.01x, r2 = 0.99). For platelet counts <20 x 10(9)/L the maximal deviation was 2
      x 10(9)/L. The correlation between automated counts and the standard method was
      poor. The regression was y = 9.63 + 0.94x, r2 = 0.86. For platelet counts <20 x
      10(9)/L the maximal deviation was 37 x 10(9)/L; on average, 7 x 10(9)/L platelets
      were counted in excess when compared with the standard method. PCW, in contrast
      to the automated impedance method, discriminated platelets from nonplatelet
      particles such as debris, fragments of red blood cells (hemolytic-uremic syndrome
      [HUS]) and of blast cells, and identified platelets of abnormal size. In
      addition, the appearance ofplatelets, WBCs, and RBCs gave clues to the etiology
      of thrombocytopenia, such as leukemia, infection, HUS, familial
      macrothrombocytopenia, and immune thrombocytopenia. PCW is a fast, reliable
      platelet counting method requiring less experience than the phase-contrast
      method. Visual evaluation from a stained smear clearly differentiates platelets
      and nonplatelet particles in contrast to most automated counters. In addition,
      the original smear can be preserved and reevaluated.

PMID- 11446658
TI  - Alloimmune thrombocytopenia in the fetus and newborn.
AB  - Alloimmune thrombocytopenia is an interesting and challenging disease.
      Identification in the fetus and newborn by screening remains to be clarified. The
      primary clinical criterion for neonatal diagnosis appears to be a neonatal
      platelet count of <50 x 10(9)/L. Treatment of the neonate can be accomplished
      with intravenous immunoglobulin (IVIG) +/- steroids or with matched platelet
      transfusion. Cranial ultrasonography is important. Testing can be performed on
      the parents and requires a highly experienced laboratory. If an affected fetus is
      identified, based on a previous affected neonate and a homozygous father,
      antenatal management is needed. Studies have been completed that inform the still
      controversial decision. IVIG remains the basis of therapy but appears to require
      a higher dose (2 g/kg/week) and/or the addition of 1 mg/kg of prednisone in the
      highest risk cases, those with antenatal intracranial hemorrhage.

PMID- 11446659
TI  - Acute immune thrombocytopenia (ITP) in childhood: retrospective and prospective
      survey in Germany.
AB  - Treatment of acute childhood immune thrombocytopenia (ITP) is controversial. For
      information on the present situation in Germany, a retrospective and a
      prospective survey were carried out. In the retrospective survey, questionnaires
      were sent to all German pediatric hospitals asking about local policies for
      handling ITP and whether in the preceding year (starting on October 1995) death
      or ICH had occurred; 86% answered. In the prospective survey, 94% responded to
      the mailings ("have you seen a case of ITP?") sent in monthly intervals between
      October 1, 1996 and September 30, 1997; 89% of the questionnaires were retrieved.
      In the retrospective survey, no deaths and no ICH were reported. If only mild
      bleedings, such as skin bleeds alone (or additional mild mucous membrane
      bleeding) were present, 20.5% (26.4%) preferred the "watchful waiting" regimen
      (supportive care), irrespective of the platelet count; 79.5% (73.6%) would treat
      if the platelet counts were <5 x 10(9)/L, 73.5% (67.9%) if < 10, 35.9% (33.6%) if
      < 20, and 4.2% (2.6%) if <30. Of the treaters, 50.5% would prefer immunoglobulins
      (Ig), 24.4% glucocorticosteroids (GC), and 20.5% GC and/or Ig. Generally, a rise
      in platelets, most frequently >50 x 10(9)/L was considered as therapeutic
      success. In the prospective survey, from the reported 323 children an annual
      incidence of 2.16 per 100,000 children was calculated. The incidence depended on
      age and gender, being highest for boys younger than 2 years with 5.8 (girls 3.42)
      and low with 0.44 for boys (girls 0.89) older than l4 years. About 60% of the
      patients had a preceding infection. Although 83% had a platelet count <20 x
      10(9)/L (56% <10 x 10(9)/L), almost all (97.5%) had only mild bleeding symptoms;
      2.5% had serious bleeding symptoms requiring blood transfusion or nasal packing,
      none had ICH, and no death was reported. The mean platelet count on admission was
      11.348 (lowest count 8.253) x 10(9)/L. Sixty-one percent received Ig, 19% GC
      (both either alone or as first choice), 6% Ig plus GC, and 14% no treatment. Side
      effects were reported in 22% of the children treated with Ig. The retrospective
      survey mirrored the uncertainty in regard to treatment. The prospective survey
      provided new aspects on incidence, age, and gender distribution. Although almost
      all patients had only mild bleeding symptoms, most received Ig and/or GC. The
      decision to treat depended mainly on the platelet count. From these surveys,
      conclusions about the effectiveness of treatment cannot be drawn. Recommendations
      based primarily on platelet counts must be reconsidered.

PMID- 11446660
TI  - The nontreatment of childhood ITP (or "the art of medicine consists of amusing
      the patient until nature cures the disease").
AB  - The management of childhood acute idiopathic thrombocytopenic purpura is
      controversial, with recent guidelines highlighting the lack of suitable evidence
      upon which to base management decisions. Three European centers have used an
      expectant policy and results over the past decade demonstrate that this is safe
      and convenient for the majority of children. Adequate parental education about
      the condition from an experienced specialist is essential, together with open
      access for children should they develop any problems. A clinical stratification
      of such patients must be incorporated into any future trials, together with
      quality of life assessment to discover the impact of restrictions on lifestyle,
      particularly in adolescents with chronic ITP who may need a different approach.

PMID- 11446661
TI  - Outcome measures and treatment endpoints other than platelet count in childhood
      idiopathic thrombocytopenic purpura.
AB  - Therapy for children with acute idiopathic thrombocytopenic purpura (ITP) has
      been controversial, in great part because it is not evidence based. Some
      physicians are activists, treaters, or interventionists with regard to therapy of
      ITP whereas others have been described as nontreaters or noninterventionists.
      Platelet count (which is often extremely low in ITP) has generally been employed
      as a surrogate measure of hemorrhagic risk even though life-threatening or fatal
      bleeding is rare. Virtually all of the randomized clinical trials conducted in
      childhood ITP have focused on platelet counts as the sole outcome measure.
      However, other determinants should influence clinical decision making, including
      assessment of bleeding tendency. Laboratory testing has not been helpful in this
      regard, but clinical assessment by means of semiquantitative bleeding scores may
      prove more useful than simply designating a patient as having a "dry" or "wet"
      purpura. The side effects as well as costs (direct and indirect) of therapy must
      also be considered when attempting to weigh the merits of drug therapy against
      their risks. Finally, the effect of ITP and its treatment on health-related
      quality of life should be determined. Measurement tools to assess each of these
      alternative outcome measures are in early stages of development. Employing them
      in addition to platelet counts in future clinical trials will allow treatment to
      be based more on scientific data than treatment philosophy.

PMID- 11446662
TI  - Function of von Willebrand factor in children with diarrhea-associated hemolytic
      uremic syndrome (D+ HUS).
AB  - Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not
      unequivocal. Because of potential pathogenic implications, we examined the
      ability of vWF to bind to collagen in vitro, which reflects its function. Plasma
      vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by
      enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+)
      HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis
      (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40)
      and from controls (n = 35). Structural vWF was evaluated by multimer analysis.
      Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The
      corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55
      and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in
      controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in
      controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated
      by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE
      (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers
      of vWF were detected in any group, including HUS. The very high concentration of
      plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In
      contrast to all other groups, only children with HUS had a dysfunctional vWF,
      caused either by a primary (due to enterohemorrhagic Escherichia coli) or
      secondary (due to consumption of functionally active vWF) process. This
      abnormality was not obvious as structural anomaly by multimer analysis.

PMID- 11446663
TI  - Heparin-induced thrombocytopenia in pediatrics.
AB  - As in adult patients, heparin is used for prophylaxis and treatment of
      thromboembolism in newborns, children, and adolescents. Patients receiving
      heparin are potentially at risk to develop heparin-induced thrombocytopenia
      (HIT). HIT type II has been extensively described in the adult population; only a
      few reports address HIT type II in pediatric patients (total of 15 neonates, 4
      young children, 12 older children and adolescents). The available data are
      discussed, and the case of a patient with recurrent thrombosis and HIT type II
      without thrombocytopenia is presented. The review of the literature reveals that
      HIT type II occurs especially in neonates and adolescents, corresponding to the
      two age peaks of thrombosis in pediatric patients. Risk factors for thrombosis
      include hereditary factors, immobilization, and surgery. HIT complications are
      severe and partly lead to life-threatening thromboembolism. In three patients, an
      increasing heparin demand was found. In five cases, thrombocytopenia was absent.
      Heparin was replaced mostly by danaparoid sodium; in three patients hirudin was
      used as an alternative anticoagulant. HIT type II represents a potentially
      dangerous complication of heparin therapy in pediatric patients and should be
      taken into consideration whenever heparin is given for prophylactic or
      therapeutic use in newborns, children, or adolescents.

PMID- 11446664
TI  - Multiple endocrine neoplasia type 1: usefulness of genetic tests in atypical
      cases.

PMID- 11446665
TI  - Novel aspects of primary alveolar hypoventilation.

PMID- 11446666
TI  - Antineutrophil cytoplasmic antibody associated microscopic polyangiitis and
      sinobronchial syndrome.

PMID- 11446667
TI  - Anti-neutrophil cytoplasmic antibodies tests: which tests should be used in
      practice?
AB  - Serological testing for anti-neutrophil cytoplasmic antibodies (ANCA) has become
      an important tool for supporting a diagnosis of systemic necrotizing small vessel
      vasculitis: Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss
      syndrome and oligo-symptomatic forms of these. These so-called ANCA-associated
      vasculitides most often necessitate the institution of therapies with cytotoxic
      as well as anti-inflammatory agents, and hence, a firmly established diagnosis is
      mandatory to avoid unnecessary and risky treatment. In the laboratory of today
      the most appropriate way to detect the presence of vasculitis-associated ANCA is
      by using both indirect immunofluorescence and direct enzyme immuno-assay for
      antibodies to proteinase 3 and myeloperoxidase. The diagnostic specificity of
      these latter assays towards systemic vasculitis can only be secured by setting a
      suitably high cut-off value, chosen in collaboration with clinicians after
      testing carefully selected disease control sera. When classical cytoplasmic ANCA
      as well as a significant level of proteinase 3-ANCA are found in a given serum
      this combined result strongly indicates vasculitis. Similarly, the combination of
      perinuclear ANCA and a significant level of myeloperoxidase-ANCA is close to 100%
      specific for vasculitis.

PMID- 11446668
TI  - Peripheral blood stem cell transplantation in patients over 65 years old with
      malignant lymphoma--possibility of early completion of chemotherapy and
      improvement of performance status.
AB  - OBJECTIVE: After the initial clinical application of peripheral blood stem cell
      transplantation (PBSCT) in the latter half of the 1980s, the frequency of PBSCT
      for non-Hodgkin's lymphoma (NHL) has been gradually increasing. At present, PBSCT
      is an important procedure for treating young patients with NHL. This procedure is
      now being increasingly used as a part of the chemotherapy regimen for elderly
      patients. We evaluated the feasibility of PBSCT in elderly patients with
      malignant lymphoma. PATIENTS AND METHODS: We performed PBSCT on four older
      patients over 65 years old (median age 71, range 66-78) with aggressive non
      Hodgkin's lymphoma. Patients were initially treated with the THP-COP
      [cyclophosphamide, THP-doxorubicin (pirarubicin), vincristine, prednisolone]
      regimen as first-line chemotherapy. As second-line chemotherapy, in partial
      response (PR) cases, we performed PBSCT. Conditioning therapy was the MCVC
      [ranimustine (MCNU), carboplatin, etoposide (VP-16), cyclophosphamide] protocol.
      RESULTS: PBSC collection and transplantation were possible in all patients. We
      observed no severe toxicity. Two of the four patients attained complete remission
      (CR). Tumor size was clearly diminished in two PR patients. Performance status
      (PS) was improved in three of the four patients after transplantation.
      CONCLUSION: Despite the small number of cases, this procedure is beneficial for
      completing chemotherapy earlier and promoting a good quality of life.

PMID- 11446669
TI  - Transesophageal echocardiography for detection of cardiac diseases in patients
      with retinal artery occlusion.
AB  - OBJECTIVE: We analyzed the usefulness of transesophageal echocardiography (TEE)
      for detection of cardiac diseases in patients with retinal artery occlusion
      (RAO). PATIENTS AND METHODS: We retrospectively reviewed the charts of 22
      consecutive patients with acute RAO. The patients had been evaluated by
      conventional studies, including transthoracic echocardiography (TTE) and TEE.
      RESULTS: TEE findings were abnormal in 13 (59%) of the 22 patients. The findings
      revealed a decrease of flow velocity in the left atrial appendage (n=7), atrial
      septal aneurysm (n=4), patent foramen ovale (n=2), spontaneous echo contrast
      (n=1), ascending aortic plaque (n=1) and left atrial thrombus (n=1). Evaluations,
      including TEE, disclosed cardiac abnormalities in 16 (73%) of these 22 patients.
      However, excluding the analysis by TEE, cardiac abnormalities were revealed in
      only 6 (27%) patients. CONCLUSION: In patients with RAO, TEE may be a useful
      examination for detecting potential cardiac diseases.

PMID- 11446670
TI  - Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for HFE
      gene.
AB  - Most patients with hereditary hemochromatosis are homozygous for C282Y in the HFE
      gene in populations of Celtic origin, but the genetic cause of this disease is
      unknown in Japan because of its rarity. A 48-year-old Japanese patient was
      recently diagnosed with idiopathic hemochromatosis. Analysis of the entire coding
      region of the patient's HFE by RT-PCR showed a heterozygous nucleotide
      substitution at nucleotide 527 from C to T, which resulted in A176V amino acid
      substitution. Another mutation at nucleotide 942 from T to C was observed, but
      this was a nonsense mutation. C282Y and another mutation, H63D, were not found in
      the patient. The mutation may have a possible role on the cause of
      hemochromatosis in this Japanese case.

PMID- 11446671
TI  - Hepatic necrosis with cholestasis induced by long-term voglibose administration.
AB  - A 76-year-old woman admitted to our hospital for jaundice had been treated for
      diabetes mellitus with insulin for 9 years and voglibose had been added for the
      39 months preceding admission. Elevated serum bilirubin and transaminase
      concentration began to normalize with initiation of corticosteroid treatment 1
      week after discontinuation of voglibose. In the in vitro testing of the patient's
      peripheral blood, lymphocytes showed stimulation by voglibose. In dramatic
      contrast to an initial liver biopsy specimen that demonstrated cholestasis with
      submassive and zonal necrosis, the follow-up specimen was normal 1 year later. We
      believe that patients treated with voglibose should be monitored long-term with
      monthly determinations of transaminases and bilirubin in serum.

PMID- 11446672
TI  - A patient with chronic hepatitis C who obtained sustained response by retreatment
      of interferon after decrease of viral load and mutation in interferon sensitivity
      determining region.
AB  - A 44-year-old man with chronic hepatitis C received three courses of interferon
      (IFN) therapy. HCV genotype was 1b, viral load was 1,200 kcopies/ml and
      interferon sensitivity determining region (ISDR) was the intermediate type before
      the 1st IFN therapy. The 1st and 2nd IFN therapies resulted in failure to yield a
      sustained response. Seven years after from the 1st therapy, viral load had
      decreased to 15 kcopies/ml and ISDR had changed to mutant type. The 3rd IFN
      therapy yielded sustained response. Thus, we should consider retreatment with IFN
      when a decrease of the viral load and change of ISDR to mutant type are observed.

PMID- 11446673
TI  - Inflammatory pseudotumor of the liver complicated with recurrent gouty arthritis.
AB  - Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion of unknown
      etiology and is often accompanied by fever. Unexplained persistent fever
      unresponsive to antibiotics developed in a 70-year-old man suffering from
      intractable recurrent gouty arthritis. 67Ga-scintigraphy disclosed intense focal
      uptake in the upper abdomen. The lesion in the left lobe of the liver was an ill
      defined hypodensity mass on computed tomographic scan and was enhanced on dynamic
      magnetic resonance imaging. The tumor was surgically removed and a diagnosis of
      IPT was made. Fever and arthritis resolved completely after surgery. Possible
      interaction between IPT of the liver and gouty arthritis was suggested.

PMID- 11446674
TI  - A germline mutation, 1001delC, of the multiple endocrine neoplasia type 1 (MEN 1)
      gene in a Japanese family.
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant inherited
      disorder characterized by tumors of the enteropancreas, parathyroid and anterior
      pituitary. The MEN 1 gene was recently cloned, and germline mutations of the gene
      have been demonstrated in cases of MEN 1. Here, we report a Japanese family with
      a germline mutation of the MEN 1 gene. The proband (44 y.o., male) had primary
      hyperparathyroidism (PHP) and pancreatic carcinoid, and his older sister (50
      y.o.) had a history of parathyroidectomy for primary hyperparathyroidism at the
      age of 40. Clinical examination revealed no evidence of PHP or other MEN 1
      related tumors in his son. Direct sequencing analysis revealed a heterozygous
      germline mutation (1001delC) at codon 297 in exon 6 of the MEN 1 gene in the
      proband and his son. Loss of heterozygosity (LOH) was also found in the resected
      parathyroid tissue of the proband. The deletion of cytosine 1001 observed in this
      case induces a frame shift, which causes the appearance of a stop codon (TAG) at
      codon 367. This mutation appears to be associated with tumors of the endocrine
      tissues in the cases studied.

PMID- 11446675
TI  - Marked uptake of technetium-99m pertechnetate by parathyroid adenoma.
AB  - We herewith report an unusual case of primary hyperparathyroidism whose
      parathyroid adenoma strongly accumulated technetium (Tc)-99m pertechnetate. A 41
      year-old woman was referred to our department under the tentative diagnosis of
      primary hyperparathyroidism. Scintigraphy by thallium-201 chloride showed
      homogeneous uptake in the whole thyroid, whereas Tc-99m image revealed a strong
      local accumulation in the middle portion of the right thyroidal lobe. Neck
      exploration revealed a 12x8x5 mm tumor in the posterolateral region of the right
      thyroidal lobe, the pathology of which was parathyroid adenoma. In addition, a
      small nodule (8 mm in diameter) with pathological findings revealing follicular
      adenoma of the thyroid, was found within the medial portion of the right
      thyroidal lobe. Both lesions were removed by surgery, and a postoperative Tc-99m
      scintigraphy no longer demonstrated a significant uptake in the right thyroidal
      lobe. Since the thyroid adenoma was too small to be detected by any scintigraphic
      study and located much closer to the median line than the site of the marked
      accumulation of Tc-99m pertechnetate, it was considered very likely that the
      parathyroid adenoma concentrated Tc-99m. Search of literature revealed that there
      have been only thirteen cases of parathyroid tumor reported to date which
      significantly accumulated Tc-99m pertechnetate. The present patient represents
      another rare case of parathyroid adenoma showing sueh an unusual scintigraphic
      image.

PMID- 11446676
TI  - Three patients with isolated adrenocorticotropin deficiency presenting with
      neuroleptic malignant syndrome-like symptoms.
AB  - We report 3 patients with isolated adrenocorticotropin (ACTH) deficiency
      presenting with neuroleptic malignant syndrome (NMS)-like symptoms. All patients
      were in their 60's or 70's and showed consciousness disturbance, a high-grade
      fever, extrapyramydal signs, and muscle enzyme elevations, which met the criteria
      for NMS. Also, they all showed hyponatremia induced by isolated ACTH deficiency.
      In addition to the standard therapy for NMS, corticosteroid supplement therapy
      was effective in all patients. There thus appear to be subjects with isolated
      ACTH deficiency among patients presenting with NMS-like symptoms, and adrenal and
      pituitary function should be checked in NMS patients with hyponatremia.

PMID- 11446677
TI  - Simultaneous onset of type 1 diabetes mellitus and painless thyroiditis following
      acute pancreatitis.
AB  - A 24-year-old female suffered from acute pancreatitis, followed by simultaneous
      onset of painless goiter, elevation of thyroid hormones and diabetic
      ketoacidosis. Two months later, her insulin secreting function was severely
      decreased and positive for anti-GAD and anti-islet cell antibodies, whereas the
      serum glucagon level was normal, suggesting an autoimmune-related destruction
      specifically of beta cells. In addition, the initial hyperthyroid state was
      followed by a hypothyroid phase which later recovered to an euthyroid state,
      suggesting an initial destruction of thyroid cells. Because anti-thyroidal
      antibodies were positive, it is likely that the thyroidal destruction was also
      autoimmune-related. This case implies common pathogenic mechanisms in the
      autoimmunity related destruction of beta cells and thyroid cells.

PMID- 11446678
TI  - Transient renal glycosuria in a patient with acute pyelonephritis.
AB  - Glycosuria was detected in a 37-year-old Chinese woman by a urinary examination
      in a local clinic with clinical evidence of acute pyelonephritis (APN). Transient
      glycosuria is an unusual complication of acute pyelonephritis in non-diabetic
      patients. As there is growing prevalence of type 2 diabetes in the population
      worldwide, it must be recognized that mistaken diagnosis of diabetes mellitus by
      glycosuria may predispose patients to an unfavorable hypoglycemic episode. Thus
      definite diagnosis of diabetes mellitus should be made only after recovery of APN
      by means of urinalysis or by simultaneous blood glucose concentration analysis.

PMID- 11446679
TI  - The spectrum of CFTR-related disease.
AB  - There is increasing appreciation for the presence of diseases which do not fit
      the criteria for classic cystic fibrosis but are caused by dysfunction of the
      cystic fibrosis transmembrane conductance regulator (CFTR). This case describes a
      patient with documented CFTR dysfunction by nasal potential difference
      measurement who presents with chronic idiopathic pancreatitis, sinusitis, and
      allergic bronchopulmonary aspergillosis (ABPA), but not congenital bilateral
      absence of the vas deferens (CBAVD) or other classic symptoms of cystic fibrosis.
      This rare case demonstrates both the spectrum of disease which can be seen with
      CFTR dysfunction and the steps required to document CFTR involvement.

PMID- 11446680
TI  - Familial adult onset primary alveolar hypoventilation syndrome.
AB  - A 41-year-old man fell into type II respiratory failure after catching a cold,
      and became dependent on a respirator. Chest radiography showed no abnormalities
      and the hyperventilation test showed improved arterial blood gas findings. His
      sleep study showed marked nocturnal desaturation due to hypopnea and apnea with a
      decrease of thoracic and abdominal movement during sleep. Therefore, we diagnosed
      him as primary alveolar hypoventilation syndrome (PAH). Seven years previously,
      his 2-year elder sister had suffered from similar respiratory failure during her
      second pregnancy and had been diagnosed as PAH. While myopathy was suspected in
      both cases, attenuation of muscle strength was slight and it appeared not to be
      the main cause of alveolar hypoventilation. Since medication was not effective in
      each case, they underwent non-invasive positive pressure ventilation (NIPPV).
      While sustained mild hypercapnia remained during the daytime, it improved their
      respiratory failure. To our knowledge, this is the first study of familial adult
      onset PAH.

PMID- 11446681
TI  - Hypertrophic pulmonary osteoarthropathy associated with non-small cell lung
      cancer demonstrated growth hormone-releasing hormone by immunohistochemical
      analysis.
AB  - Hypertrophic pulmonary osteoarthropathy (HPO) associated with non-small cell lung
      cancer in a 58-year-old man was accompanied by an elevated serum level of growth
      hormone (GH). HPO rapidly disappeared after resection of the primary tumor and
      the elevation of serum GH was resolved. Immunohistochemically the tumor contained
      growth hormone-releasing hormone (GHRH) but not GH. These findings suggest that
      the high serum GH level due to ectopic GHRH production in the tumor, was a
      contributing factor in HPO. This is the second reported case of non-small cell
      lung cancer which was immunohistochemically positive for GHRH associated with
      HPO.

PMID- 11446682
TI  - Malignant fibrous histiocytoma of soft tissue producing granulocyte colony
      stimulating factor.
AB  - We treated a rare case of malignant fibrous histiocytoma (MFH) of soft tissue
      that produced granulocyte colony-stimulating factor (G-CSF). The patient, an 80
      year-old woman, was admitted because of a feeling of abdominal fullness and leg
      edema. An elastic, hard, tender tumor was palpated in the right thigh.
      Histopathological examinations of the tumor revealed atypical and prominent
      pleomorphic spindle-shaped cells with funicular arrangement, which were
      compatible with the diagnosis of MFH. Prominent leukocytosis (up to
      84,300/microl), a high serum G-CSF concentration (82 pg/ml) and positive
      immunohistochemical staining of the tumor tissue for G-CSF indicated that G-CSF
      was produced by the MFH.

PMID- 11446683
TI  - Acquired hemophilia A in a patient with systemic lupus erythematosus.
AB  - A patient with systemic lupus erythematosus (SLE) developed acquired hemophilia
      A. The patient, a 24-year-old Japanese woman, was referred to our hospital
      because of uncontrollable bleeding following a tooth extraction. Laboratory
      examination revealed prolonged APTT (116 seconds), reduced factor VIII activity
      (2.8 %) and the presence of factor VIII inhibitor at a titer of 46.5 Bethesda
      units/ml. Transfusion of prothrombin complex concentrate and activated
      prothrombin complex concentrate followed by administration of prednisolone and
      cyclophosphamide successfully arrested bleeding and reduced the factor VIII
      inhibitor level. Acquired hemophilia A is a rare but lethal condition. Rapid
      diagnosis and introduction of adequate therapies are critical.

PMID- 11446684
TI  - Microscopic polyangiitis associated with sinobronchial syndrome.
AB  - A woman with a long history of chronic bronchitis and chronic sinusitis, i.e.,
      sinobronchial syndrome, was admitted with a fever. Radiologically, there were
      areas of longstanding consolidation in both lungs, with areas of active
      inflammation demonstrated by gallium-67 scintigraphy. Antineutrophil cytoplasmic
      antibody specific for myeloperoxidase was highly positive. Pulmonary hemorrhage
      and hematuria occurred 2 weeks after admission and responded to steroid therapy.
      However, the patient died of pneumonia. An autopsy revealed systemic necrotizing
      vasculitis affecting multiple organs, consistent with microscopic polyangiitis.
      The vasculitis might have been caused by the chronic inflammation in the lungs
      associated with sinobronchial syndrome.

PMID- 11446685
TI  - Hypoceruloplasminemia in neurological diseases.

PMID- 11446686
TI  - Disappearance of spironolactone-induced gynecomastia with triamteren.

PMID- 11446687
TI  - Rhabdomyolysis and acute renal failure after poisonous snake (Agkistrodon halys
      blomhoffii) bite.

PMID- 11446688
TI  - Guillain-Barre syndrome associated with herpes zoster.

PMID- 11446689
TI  - An ab-initio study of the C3H6-HX, C2H4-HX and C2H2-HX hydrogen-bonded complexes
      with X=F or Cl.
AB  - MP2/6-31G** ab-initio molecular orbital calculations have been performed to
      obtain geometries, H-bond energies and vibrational properties of the C3H6-HX,
      C2H4-HX and C2H2-HX H-bonded complexes with X=F or Cl. The more pronounced
      effects on the structural parameters of the isolated molecules due to
      complexation are verified to the CC and HX bond lengths, which are directly
      involved in the H-bond formation. They are increased after complexation. The
      calculated H-bond lengths for the hydrogen complexes for X=F are shorter than
      those for x-Cl by about 0.55 A, whereas the corresponding experimental value is
      0.58 A. The H-bond energies are essentially determined by the nature of the
      proton donor molecule. For X=F, the AE mean value is 20 kJ/mol, whereas it is
      approximately 14.5 kJ/mol for X-Cl. The H-bond energies including zero-point
      corrections show a good correlation with the H-bond lengths. The more pronounced
      effect on the normal modes of the isolated molecules after complexation occurs to
      the H-X stretching mode. The H-X stretching frequency is shifted downward,
      whereas its IR intensity is much enhanced upon H-bond formation. The new
      vibrational modes arising from complexation show several interesting features.

PMID- 11446690
TI  - Ultrasonic frequencies calculated for the q[100] mode in the first-order,
      tricritical and the second-order phase transitions of NH4Cl.
AB  - This study correlates the volume changes to the ultrasonic frequencies of the
      q[100] mode of NH4Cl for the first-order, tricritical and the second-order phase
      transitions in this crystal. Using these correlations we were able to calculate
      the ultrasonic frequencies of this mode at the pressures of 0, 0.6 and 1.1 kbar
      (first-order), 1.6 kbar (tricritical) and 2.15 kbar (second-order) by means of
      the volume change data from the literature. Our calculated frequencies are in
      good agreement with the observed data for the phase region below the critical
      temperature T(C) for the first-order, tricritical and the second-order phase
      transitions in NH4Cl. Above T(C) our calculated frequencies do not agree
      satisfactorily for the q[100] mode and it is incapable of explaining the observed
      behaviour of NH4Cl. Our method of calculating the ultrasonic frequencies is
      presented.

PMID- 11446691
TI  - Spectral characteristics of 2-aminodiphenylamine in different solvents and at
      various pH values.
AB  - The absorption and fluorescence spectra of 2-aminodiphenylamine (2ADA) have been
      studied as a function of solvent polarity and acid concentration. Analysis of
      solvatochromic and prototropic shifts of 2ADA reveals: (i) the presence of
      intramolecular hydrogen bonding between imino and amino groups in the ground
      state, (ii) dual fluorescence (360 and 430 nm) of the monocation (2ADA+) formed
      by the protonation of amino group; and (iii) proton-induced quenching of the
      monocation (2ADA+) fluorescence. In the dual fluorescence of 2ADA+, the longer
      wavelength emission at 430 nm is found to be from the twisted form of the
      monocation. The rate constants of the proton-induced quenching of 2ADA+ are
      determined.

PMID- 11446692
TI  - The infrared fundamental intensities and polar tensor of allene.
AB  - The polar tensor of allene was calculated from the infrared fundamental band
      intensities of C3H4 and C3D4. The ambiguities in the signs of the dipole moment
      derivatives with respect to their normal coordinates were resolved by comparison
      of tensor elements with ab initio calculations at the B3LYP, MP2(FC) and CCD(FC)
      levels with a 6/311 + + G(3d,3p) basis set. The results are similar to those
      previously obtained by Koga and co-workers except for the choice of an average of
      two sign combinations for the E symmetry elements. The values of the mean dipole
      moment derivatives for the sp and sp2 carbon atoms obtained in this work, 0.032
      and -0.133 e, respectively, are in good agreement with the CCD(FC)/6-311 + +
      G(3d,3p), 0.061 and -0.128 e, and MP2(FC)/6-311 + + G(3d,3p), 0.072 and -0.153 e,
      theoretical results. The mean dipole moment derivatives are shown to be
      consistent with potential models relating 1s electron ionization energies and
      atomic charges.

PMID- 11446693
TI  - Laser-induced fluorescence studies of polycyclic aromatic hydrocarbons (PAH)
      vapors at high temperatures.
AB  - In this work, we present the fluorescence spectra of anthracene and pyrene vapors
      at different elevated temperatures (from 150 to 650 degrees C) excited with the
      337 nm line of a nitrogen laser. We describe the high temperature effects on the
      resulting spectral properties including spectral intensity, spectral bandwidth
      and spectral shift. We found that the PAH fluorescence spectral bandwidths become
      very broad as the temperature increases. The broadening is mainly due to thermal
      vibrational sequence congestion. We also have found that the fluorescence
      intensity of pyrene vapor increases with increasing temperature, which results
      from the increase of the pyrene vapor absorption cross section at 337 nm.

PMID- 11446694
TI  - Normal coordinate analysis of 4-aminopyridine. Effect of substituent on pyridine
      ring in metal complexes of 4-substituted pyridines.
AB  - The normal coordinate analysis has been performed for 4-aminopyridine (4-apy)
      assuming C2v molecular symmetry. A Urey-Bradley force field has been used. The
      force constants are adjusted to fit the observed frequencies for 4-apy and its
      deuterated species. The vibrational assignment has been made on the basis of the
      calculated frequencies and potential energy distributions. The calculated
      frequencies were in good agreement with the observed frequencies. The substituent
      effect upon the M-nitrogen (ligand) (L = 4-methlypyridine, 4-ethylpyridine, 4
      vinylpyridine. 4-aminopyridine and 4-cyanopyridine) and pyridine ring frequencies
      has also been investigated. The frequency shifts are found to be sensitive to the
      substituent in the 4-position of the pyridine ring.

PMID- 11446695
TI  - Inelastic neutron scattering and infrared spectroscopic study of furan adsorption
      on alkali-metal cation-exchanged faujasites.
AB  - Inelastic neutron scattering (INS) as well as infrared (IR) transmission and
      diffuse reflection infrared Fourier transform (DRIFT) spectra of furan adsorbed
      on Li-LSX, NaY, NaX, K-LSX, and CsNaX zeolites have been measured in the range
      2000-200 and 4000-1300 cm(-1), respectively. On the basis of an assignment of
      normal modes of furan taken from the literature and our own quantum chemical
      calculations of vibrational frequencies, the observed frequency shifts between
      bulk furan and furan adsorbed on the zeolites mentioned above have been
      interpreted in view of the interactions between furan and zeolite. For an
      explanation of frequency shifts of CH out-of-plane bendings, CH stretchings and
      some ring vibrations, it has to be assumed that in addition to the interaction
      between furan and the corresponding cation of the zeolite, a further interaction
      between the CH bonds and lattice oxygen atoms exists.

PMID- 11446696
TI  - Ab-initio molecular geometry and normal coordinate analysis of
      tetrahydrothiophene molecule.
AB  - The molecular geometry of tetrahydrothiophene (THT) was quantum mechanically
      calculated using the split valence 6-31G** basis set. Electron correlation energy
      has been computed employing MP2 method. The molecule showed a twist form puckered
      structure with a twist torsion angle of 13 degrees and has a total energy of 
      347,877.514 kcal/mol of which a 436.715 kcal/mol electron correlation energy. The
      envelope form of the molecule showed an inter-plane angle of 22 degrees and has a
      total energy of -347,874.430 kcal/mol involving -436.558 kcal/mol electron
      correlation energy. The normal coordinates of the molecule were theoretically
      analyzed and the fundamental vibrational frequencies were calculated. The IR and
      laser Raman spectra of THT molecule was measured. All the observed vibrational
      bands including combination bands and overtones were assigned to normal modes
      with the aid of the potential energy distribution values obtained from normal
      coordinate calculations. The molecular force field was determined by refining the
      initial set of force constants using the least square fit method instead of using
      the less accurate scaling factor methods. The determined molecular force field
      has produced simulated frequencies which best match the observed values. The
      lowest-energy modes of vibration were two molecular out-of-plane deformations,
      observed at 114 and 166 cm(-1). The barrier of ring twisting estimated from the
      observed ring out-of-plane vibrational mode at 114 cm(-1) was estimated.

PMID- 11446697
TI  - Determination of the quadratic hyperpolarizability of trans-4-[4
      (dimethylamino)styryl]pyridine and 5-dimethylamino-1,10-phenanthroline from
      solvatochromism of absorption and fluorescence spectra: a comparison with the
      electric-field-induced second-harmonic generation technique.
AB  - For fluorescent compounds, the combined use of absorption and emission
      solvatochromic data allows to estimate indirectly the cavity radius of the
      molecule in solution, a very critical parameter in the application of the
      solvatochromic method for the determination of the quadratic hyperpolarizability
      beta of dipolar molecules. For two test compounds, trans-4-[4
      (dimethylamino)styryl]pyridine (DASP) and 5-dimethylamino-1,10-phenanthroline
      (DAPHEN), the beta values so obtained are compared with those obtained by the
      EFISH (Electric Field Induced Second-Harmonic generation) technique. For DAPHEN,
      the versatility of the method described in this work in the presence of more than
      one electronic transition contributing to the non-linear optical response is
      demonstrated.

PMID- 11446698
TI  - Studies on unimolecular and bimolecular photoprocesses of a newly synthesized
      selenium compound, 7-chloro-2-phenyl-9H-[1]-benzopyrano[3,2-b]-selenophene-9-one
      (SeP).
AB  - Using steady state/time resolved spectroscopic and electrochemical techniques the
      spectroscopic and photophysical studies were made on a novel synthesized
      selenophene compound SeP in nonpolar methylcyclohexane (MCH), polar aprotic
      acetonitrile (ACN) and polar protic ethanol (EtOH) solvents at the ambient
      temperature as well as at 77 K. Both from the studies on unimolecular and
      bimolecular photoprocesses this selenophene compound was found to possess several
      electronic levels, 1Bb, 1La, 1Lb (all are of pi pi* nature and 1Lb is hidden
      within 1La band envelop like the characteristics of most of the acenes) and 1(nO
      pi*) state arising due to carbonyl oxygen atom. In polar ACN environment this nO
      pi* state disappears because it moves within the envelop of intense 1La band due
      to large destabilization. Large overlapping of different band systems within the
      1La band of SeP was confirmed from the observed depolarization effect. The lack
      of phosphorescence of SeP both in MCH and EtOH rigid glassy matrix at 77 K has
      been inferred due to large vibronic interactions between closely lying triplets
      of the corresponding 1nO pi* and 1Lb states. From the bimolecular investigations,
      it reveals that SeP acts as a good electron donor in presence of the well known
      electron acceptor 9 cyanoanthracene (9CNA). Transient absorption spectra measured
      by laser flash photolysis technique demonstrate the formation of ion-pair when
      the acceptor is excited. From the analysis of the fluorescence quenching data it
      seemingly indicates that the major contribution in the diminution of the
      fluorescence intensity of the acceptor 9CNA in presence of SeP is not only due to
      the photoinduced electron transfer (ET) but also originates from static type
      (instantaneous) quenching processes along with external heavy atom effect. The
      possibility of occurrence of photoinduced ET reaction in Marcus inverted region
      is hinted.

PMID- 11446699
TI  - Copper(II) ion induced monolayer formation of p-tert-butylthiacalix[4]arene at
      the air-water interface.
AB  - The monolayer properties of p-tert-butylthiacalix[4]arene (TCA) at the air-water
      interface was investigated by the measurements of surface pressure-area
      isotherms. However, TCA only exists as a trimmer aggregate on the subphase of
      deionized water. Copper(II) ion in the subphase can induce the monolayer
      formation of TCA. The UV-Vis spectra and FTIR spectra of the transferred films
      suggested that the monolayer forrmation was fulfilled through the coordination of
      copper(II) ion to TCA at the air-water surface.

PMID- 11446700
TI  - The influence of molecular symmetry and topological factors on the internal heavy
      atom effect in aromatic and heteroaromatic compounds.
AB  - The absorption and fluorescence properties of 26 specially selected aromatic and
      heteroaromatic compounds, from different classes, are studied quantum chemically
      and experimentally at room temperature (293 K). Seven of these compounds have not
      been studied before. The compounds are arranged in seven groups, which illustrate
      different cases of the internal heavy atom effect. The quantum yield of
      fluorescence, gamma and fluorescence decay time, tau(f) of deaerated and non
      deaerated cyclohexane or ethanol solutions are measured. The oscillator strength,
      f(e), fluorescence rate constant, k(f), natural lifetime, tau(0)t, and
      intersystem crossing rate constant, kST, were calculated for each compound. The
      orbital nature of the lowest excited singlet state and direction of polarization
      of the S0 --> S1 transitions are determined using the PPP-Cl method for each
      molecule. The investigation shows that substitution of a heavy atom(s) (Cl, S,
      Br, I etc.) into an aromatic or heteroaromatic molecule may produce different
      changes in all the fluorescence parameters (sometimes dramatically) and not
      necessarily lead to the quenching of fluorescence. Substitution of a heavy
      atom(s) may increase the value of the spin-orbit operator, Hso, if the S0 --> S1
      excitation is localized to some extent on a carbon atom bonded to a heavy atom(s)
      or on the heavy atom itself (O or S). Such substitution may change the symmetry
      of a molecule and hence the values of the [psiS1/Hso/psi'T1] matrix elements
      would change (in molecules of higher symmetry groups not all Ti states are able
      to mix with the perturbing S1 state). Such substitution may change the
      arrangement of Ti states below the S1, state and hence, the Franck-Condon factors
      would change. Such substitution may also change the value of the [psiS0/Mj/psiS1]
      matrix element and, consequently, the oscillator strength of the S0 --> S1
      transition would change. A combination of all these possible changes determines
      the value of k(f) and kST and, consequently, determines the value of gamma and
      tau(f). It is observed that in many cases, the value of the spin-orbit operator
      is related to the dipole moment operator, e.g. if the introduction of a heavy
      atom increases kST then, as a rule, it decreases f(e)(1A --> 1La).

PMID- 11446701
TI  - Study of the formation equilibria of electron donor-acceptor complexes between
      [60]fullerene and methylbenzenes by absorption spectrometric method.
AB  - The electron donor-acceptor (EDA) interaction between [60]fullerene and three
      methylbenzenes, viz., durene, pentamethylbenzene and hexamethylbenzene has been
      studied in carbon tetrachloride medium at a number of temperatures. It has been
      found that these methylbenzenes form stable 1:1 EDA complexes with [60]fullerene.
      Charge transfer (CT) absorption bands of the complexes in the 410-460 nm region
      are more intense than the usual 420-700 nm absorption band of C60. The CT
      transition energies (hvCT) of the complexes change systematically with change in
      the number and position of the methyl groups in the donor molecules
      (methylbenzenes) and also with the donor ionisation potentials. From an analysis
      of this variation the electron affinity of C60 has been found to be 2.30 eV and
      also an inductive effect Huckel parameter of the methyl group has been
      determined. Formation constants (K) have been determined at three different
      temperatures from which the enthalpies and entropies of formation of the
      complexes have been determined.

PMID- 11446702
TI  - Potential energy distributions and potential scans for the internal rotation of
      two rotors in 3,3-dichloro and 3,3,3-trichloropropanals.
AB  - The conformational behavior and structural stability of 3,3-dichloropropanal and
      3,3,3-trichloropropanal were investigated by ab initio calculations. The 6-311 +
      + G** basis set was employed to include polarization and diffuse functions in the
      calculations at B3LYP level. From the calculation, the trans conformer of 3,3,3
      trichloropropanal was predicted to be the predominant conformer with about 2 kcal
      mol(-1) of energy lower than the cis form. Additionally, 3,3 dichloro-propanal
      was predicted to exist as a mixture of three stable conformers. The potential
      function scans were calculated for the two molecules from which the rotational
      barriers could be estimated. The vibrational frequencies were computed at B3LYP
      level and complete vibrational assignments were made based on normal coordinate
      calculations for the conformers of the two molecules. Vibrational Raman and
      infrared spectra of the mixture of the stable conformers were computed at 300 K.

PMID- 11446703
TI  - Library of FT-Raman spectra of pigments, minerals, pigment media and varnishes,
      and supplement to existing library of Raman spectra of pigments with visible
      excitation.
AB  - Sixty pigments, minerals and media have been analysed by Fourier-transform Raman
      (FT-Raman) microscopy in order to assemble a database of reference FT-Raman
      spectra for scientists working at the Arts-Science interface. An earlier library
      of Raman spectra compiled using visible excitation has been extended by the
      addition of 22 further reference spectra obtained with 780.0, 647.1, 632.8 and/or
      514.5 nm excitation. The relative merits of 1064 nm and visible excitation are
      discussed.

PMID- 11446704
TI  - Interactions of cyanine dyes with nucleic acids. XXIV. Aggregation of monomethine
      cyanine dyes in presence of DNA and its manifestation in absorption and
      fluorescence spectra.
AB  - Absorption, fluorescence emission and excitation spectra of benzothiazole cyanine
      dyes--thiazole orange (TO) and 7-methyl-6-(3-methyl-2,3-dihydro-1,3-benzothiazol
      2-ylidenmethyl) [1,3] dioxolo [4',5':4,5] benzo [d] [1,3] thiazolium
      methylmethosulfate (Cyan 13)--were investigated over a wide concentration range.
      The dyes form aggregates with a 'sandwich'-like structure in water solution. At
      low dye to DNA concentrations ratios, Cyan 13 and TO monomers appear to interact
      with the DNA. On increasing the dye to DNA concentrations ratio, free dye
      molecules aggregate with the DNA-bound ones. The spectra of the free dye
      aggregates and the aggregates formed on the DNA, are characterized by an
      anomalously large (more than 100 nm) Stokes shift. This suggests, that the pi
      electron systems of the aggregates undergo substantial changes in excited state,
      compared to those of the monomers. The formation of aggregates consisting of the
      free and DNA-bound dye molecules can be explained using the half-intercalation
      model of the interaction of the cyanine dye monomers with the DNA.

PMID- 11446705
TI  - Interaction of cyanine dyes with nucleic acids. XXV. Influence of affinity
      modifying groups in the structure of benzothiazol-4-[2,6-dimethylpyridinium] dyes
      on the spectral properties of the dyes in the presence of nucleic acids.
AB  - Novel monomethine pyridinium cyanine dyes of similar structure and containing
      'affinity-modifying' groups of different chemical nature were studied by spectral
      luminescent methods as possible fluorescent probes for the nucleic acids
      detection. It was shown that the nature of the functional groups in the dye
      linker influences the fluorescent properties of the dye-nucleic acids complexes.
      Incorporation of a hydroxyl group into the linker structure leads to a
      significant increase in the fluorescence intensity of the dye--double-stranded
      DNA complexes relative to the parent dye Cyan 40.

PMID- 11446706
TI  - Diagnosis of myocardial ischemia in hypertensive patients.
AB  - Arterial hypertension can provoke a reduction in coronary flow reserve through
      several mechanisms that are not mutually exclusive (i.e. epicardial coronary
      artery disease (CAD), left ventricular hypertrophy and structural and/or
      functional microvascular disease). These different targets of arterial
      hypertension should be explored with different diagnostic markers. In fact,
      stress-induced wall motion abnormalities are highly specific for angiographically
      assessed epicardial CAD, whereas ST segment depression and/or myocardial
      perfusion abnormalities are frequently found with angiographically normal
      coronary arteries associated with left ventricular hypertrophy and/or
      microvascular disease. Exercise-electrocardiography stress test can be used to
      screen patients with negative maximal test due to its excellent negative
      predictive value, which is high and comparable in normotensives and
      hypertensives. When exercise-electrocardiography stress test is positive (or
      uninterpretable or ambiguous), an imaging stress-echo test is warranted for a
      reliable identification of significant, prognostically malignant epicardial CAD
      in view of an ischemia-guided revascularization.

PMID- 11446707
TI  - Tracking of blood pressure in Australian children.
AB  - OBJECTIVE: Tracking of blood pressure (BP) from childhood occurs in populations
      but, for individuals, prediction of adult BP from childhood levels is poor. We
      examined factors that may influence tracking of BP to identify better predictors
      of higher BP in early adult life. DESIGN: A prospective study of children
      recruited at the age of 9 years by random sampling of Perth metropolitan schools
      stratified by socio-economic status. SETTING: Community based with re-surveys 3
      yearly for 9 years. PARTICIPANTS: A total of 516 boys and 520 girls at 9 years;
      680 boys and 630 girls at 12 years; 318 boys and 300 girls at 15 years; 330 men
      and 326 women at 18 years. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic
      (DBP) BP. RESULTS: Persistence in the highest quartile for SBP between surveys
      was seen in 34-48% of subjects and in 37% between the ages of 9 and 18 years. The
      proportion increased to around 60% in those in the highest quartile for body mass
      index (BMI), to 70% in those in the highest quartile for change in BMI and to 60%
      if there was a family history of hypertension. In log-linear models, persistence
      in a quartile for SBP was significantly related to a family history of
      hypertension, previous SBP, BMI and change in BMI. Relationships were similar for
      DBP. CONCLUSIONS: Excessive weight gain in adolescence and a family history of
      hypertension substantially increase the risk of higher BP persisting into early
      adult life. Recognition of children at risk would allow early intervention
      emphasizing weight control with potential long-term benefits.

PMID- 11446708
TI  - Prediction of blood pressure level and need for antihypertensive medication: 10
      years of follow-up.
AB  - OBJECTIVE: To evaluate the usefulness of blood pressure and its variability in
      the prediction of future blood pressure and need for antihypertensive medication.
      METHODS: We used WHO criteria to classify, at baseline, 97 healthy untreated male
      volunteers as normotensive (n = 34), borderline hypertensive (n = 29) or mild
      hypertensive (n = 34), with casual measurements before intra-arterial 24 h
      ambulatory blood pressure monitoring. After 10 years of follow-up, 87 of the men
      (90%) were available and their blood pressure was recorded using casual
      measurements and non-invasive ambulatory 24 h monitoring. RESULTS: During the
      follow-up, the blood pressure classification deteriorated in 35 individuals (40%)
      and improved in six (7%) (McNemar test, P< 0.0001). In the borderline
      hypertensive group, 77% became hypertensive (P= 0.03). The 24 h mean systolic
      blood pressure was the best predictor of follow-up casual systolic (adj.R2 =
      0.420) and 24 h systolic (adj.R2 = 0.540) blood pressure. The 24 h mean diastolic
      blood pressure was the best predictor of follow-up casual diastolic (adj.R2 =
      0.301) and 24 h diastolic (adj.R2 = 0.292) blood pressure. The baseline casual
      systolic blood pressure also predicted the follow-up casual systolic blood
      pressure relatively well (adj.R2 = 0.356), but was clearly weaker for the follow
      up 24 h systolic (adj.R2 = 0.275) blood pressure. The prediction of follow-up
      casual diastolic (adj.R2 = 0.259) and follow-up 24 h diastolic (adj.R2 = 0.214)
      blood pressure by baseline casual blood pressure was even weaker. The means and
      variabilities of the 24 h, daytime, and night-time blood pressures were the best
      predictors of the need for antihypertensive medication (Cox-Snell R2 = 0.399).
      The characteristics of the individual did not significantly predict future blood
      pressure and the need for antihypertensive medication. CONCLUSIONS: The 24 h mean
      blood pressure was an excellent predictor of the future blood pressure and the
      need for antihypertensive medication. Prediction of antihypertensive medication
      was further improved by also using blood pressure variability. Systolic blood
      pressure was more predictable than diastolic blood pressure.

PMID- 11446709
TI  - Blood pressure increase between 55 and 68 years of age is inversely related to
      lung function: longitudinal results from the cohort study 'Men born in 1914'.
AB  - BACKGROUND: Although age is associated with increasing blood pressure, there is a
      substantial heterogeneity within a certain birth cohort. Whether increase in
      systolic and diastolic blood pressure is related to pulmonary function is largely
      unknown. OBJECTIVE: To study blood pressure elevation between 55 and 68 years of
      age in relation to vital capacity (VC) and forced expiratory volume (FEV1.0) at
      55. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 375 men
      without antihypertensive medication at baseline. MAIN OUTCOME MEASURE: Change in
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) over 13 years.
      RESULTS: Blood pressure increase between 55 and 68 years was highest among men
      who at 55 years had low vital capacity. Average increase in systolic blood
      pressure for men with vital capacity in the first, second, third and fourth
      quartile was 20.4, 18.7, 16.5 and 11.1 mmHg, respectively (P for trend = 0.005).
      Average increase in diastolic blood pressure was 10.6, 9.9, 9.0 and 6.3 mmHg,
      respectively (P= 0.02). The trends remained statistically significant after
      adjustments for baseline blood pressure, tobacco consumption, smoking cessation
      between 55 and 68, weight change between 55 and 68, physical activity and
      diabetes. Further analysis showed that the relationships could be found among men
      with blood pressures < or = 140/ 90 mmHg at baseline, whereas no significant
      association was found for men whose baseline SBP or DBP exceeded 140/90 mmHg.
      FEV1.0 showed similar associations with change in blood pressure. CONCLUSION:
      Lung function is inversely associated with future blood pressure increase. It is
      suggested that this association could contribute to the relationships between
      lung function and incidence of cardiovascular disease.

PMID- 11446710
TI  - Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese
      men: The Osaka Health Survey.
AB  - OBJECTIVE: To investigate the association of serum uric acid level with the risk
      for hypertension and Type 2 diabetes. DESIGN: Prospective cohort study. SETTING:
      Work site in Osaka, Japan. PARTICIPANTS: A total of 6,356 Japanese men, aged 35
      60 years with systolic blood pressure < 140 mmHg and diastolic blood pressure <
      90 mmHg, normal glucose intolerance, and no history of hypertension or diabetes
      at baseline. MAIN OUTCOME MEASURES: Blood pressure was measured by standard
      techniques, using 160/95 mmHg for diagnosis of hypertension. Type 2 diabetes was
      defined as a fasting plasma glucose level > or = 126 mg/dl or a 2 h post-loaded
      plasma glucose level > or = 200 mg/dl. RESULTS: During the 61,716 person-years
      follow-up period, we confirmed 639 cases of hypertension and 454 cases of Type 2
      diabetes. Serum uric acid level was associated with an increased risk for
      hypertension but not for Type 2 diabetes. After adjustment for known risk
      factors, including daily alcohol consumption, the serum uric acid level was
      associated with an increased risk for hypertension; the relative risks for
      hypertension were 1.00 for quintile 1 of the serum uric acid level, 1.24 [95%
      confidence interval (CI), 0.94-1.65] for quintile 2, 1.34 (CI, 1.03-1.76) for
      quintile 3, 1.76 (CI, 1.35-2.29) for quintile 4, and 2.01 (CI, 1.56-2.60) for
      quintile 5 (P for trend < 0.001). Even among both non-drinkers and lean subjects,
      serum uric acid level was associated with an increased risk for hypertension.
      CONCLUSIONS: Serum uric acid level was associated with an increased risk for
      hypertension but not for Type 2 diabetes.

PMID- 11446711
TI  - Genetic contribution to the variance in left ventricular mass: the Tecumseh
      Offspring Study.
AB  - OBJECTIVE: To estimate the contribution of heredity to the variance in left
      ventricular mass (LVM), and to ascertain whether genetic factors may interact
      with non-genetic factors in promoting LVM growth. SUBJECTS AND SETTING: The study
      population consisted of 290 healthy parents and 251 healthy children living in
      Tecumseh, Michigan, USA. MAIN OUTCOME MEASURE: Correlation of parents' LVM with
      offspring's LVM adjusting for a number of clinical variables. METHODS: LVM in
      parents and offspring was measured with M-mode echocardiography by the same
      investigators. RESULTS: Parents unadjusted LVM was unrelated to offspring
      unadjusted LVM, but after removing the confounding effect of age, sex,
      anthropometric measurements, systolic blood pressure, plasma insulin and urinary
      sodium excretion, parent-child correlation for LVM was 0.28 (P = 0.006). The
      relative contribution of parental-adjusted LVM and of several offspring
      phenotypic and environmental variables on offspring LVM was evaluated by
      multivariable regression analysis. When age, gender, anthropometric measurements
      and systolic blood pressure were accounted for, adjusted LVM of parents explained
      only 1.6% of the total variance in offspring LVM. However, after inclusion of
      insulin and urinary sodium in the model heredity explained 7.6% of the total
      variance in offspring LVM, and its predictive power was second only to that of
      child's height. Furthermore, an interactive effect of parental LVM with offspring
      systolic blood pressure was found on child's left ventricular mass. CONCLUSION:
      Heredity can explain a small, but definite proportion of the variance in LVM.
      Higher blood pressure favors the phenotypic expression of the genes that regulate
      LVM growth.

PMID- 11446712
TI  - Differential nNOS gene expression in salt-sensitive and salt-resistant Dahl rats.
AB  - BACKGROUND: Several indications exist to suggest that an impaired production of
      nitric oxide might have a role in the development of salt-sensitive hypertension.
      OBJECTIVE: To examine whether the gene expression of the nitric oxide synthases
      (NOS) is altered in the salt-sensitive Dahl rat compared with that in the salt
      resistant Dahl rat. DESIGN AND METHODS: The abundance of NOS mRNA was measured by
      RNase protection assay in different organs of salt-resistant and salt-sensitive
      Dahl rats. In addition, the zonal expression of NOS genes in the kidney under
      salt load and salt restriction was determined. RESULTS: The abundance of
      endothelial NOS mRNA was similar between the salt-resistant and salt-sensitive
      Dahl rat strains in all organs. Inducible NOS mRNA was not detectable by RNase
      protection assay in any organ. Neuronal NOS (nNOS) mRNA expression, however, was
      about 50% lower in brain and kidney of salt-sensitive Dahl rats than in salt
      resistant Dahl rats. Within the kidney, nNOS mRNA levels were significantly
      decreased in salt-sensitive Dahl rats compared with those in salt-resistant Dahl
      rats, in cortex, outer and inner medulla (50, 40 and 30%, respectively) under all
      dietary conditions. A comparison of renal nNOS gene expression in Dahl rats with
      that in salt-insensitive Sprague- Dawley rats revealed that the abundance of
      renal nNOS was similar in salt-sensitive Dahl and Sprague-Dawley rats, but was
      increased in salt-resistant Dahl rats relative to that in Sprague-Dawley rats.
      CONCLUSION: These data suggest that nNOS gene expression is increased in salt
      resistant Dahl rats compared with that in salt-sensitive Dahl rats. This
      increased nNOS expression of the salt-resistant Dahl strain might play a part in
      compensating for a defect of renal salt excretion in the Dahl strains.

PMID- 11446713
TI  - Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on
      aortic vascular reactivity in hypertensive rats.
AB  - BACKGROUND: Peroxynitrite (ONOO-), the product of superoxide and nitric oxide,
      seems to be involved in vascular alterations in hypertension. OBJECTIVES: To
      evaluate the effects of ONOO- on endothelium-dependent and independent aortic
      vascular responsiveness, oxidized/reduced glutathione balance (GSSG/GSH),
      malondialdehyde aortic content, and the formation of 3-nitrotyrosine (3-NT), a
      stable marker of ONOO-, in N-acetylcysteine (NAC)-treated normotensive Wistar
      Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). RESULTS: In SHR only,
      NAC significantly reduced heart rate and systolic, but not diastolic, blood
      pressure. It also improved endothelium-dependent aortic relaxation in SHR, but
      not after exposure to ONOO-. Endothelium-dependent and independent aortic
      relaxations were markedly impaired by ONOO- in both strains of rat. NAC partially
      protected SHR against the ONOO- -induced reduction in endothelium-independent
      relaxation. Aortic GSSG/GSH ratio and malondialdehyde, which were higher in SHR
      than in WKY rats, showed a greater increase in SHR after exposure to ONOO-. NAC
      decreased GSSG/GSH and malondialdehyde in both strains of rat before and after
      exposure to ONOO-. The 3-NT concentration, which was similar in both strains of
      rat under basal conditions, was greater in SHR than in WKY rats after the
      addition of ONOO-, with a reduction only in NAC-treated SHR. CONCLUSIONS: These
      findings suggest an increased vulnerability of SHR aortas to the effects of ONOO-
      as compared with those of WKY rats. The selective improvements produced by NAC,
      in systolic arterial pressure, heart rate, aortic endothelial function, ONOO- 
      induced impairment of endothelium-independent relaxation, aortic GSSG/GSH
      balance, malondialdehyde content and 3-NT formation in SHR suggest that chronic
      administration of NAC may have a protective effect against aortic vascular
      dysfunction in the SHR model of hypertension.

PMID- 11446714
TI  - Increased generation of superoxide by angiotensin II in smooth muscle cells from
      resistance arteries of hypertensive patients: role of phospholipase D-dependent
      NAD(P)H oxidase-sensitive pathways.
AB  - OBJECTIVE: We tested the hypothesis that increased responsiveness of
      phospholipase D (PLD) to angiotensin II (Ang II) is associated with increased
      oxidative stress and exaggerated growth responses in vascular smooth muscle cells
      (VSMC) from untreated essential hypertensive patients. DESIGN: VSMCs from
      peripheral resistance arteries of normotensive and hypertensive subjects were
      studied. Production of reactive oxygen species (ROS) was measured with the
      fluoroprobe 5-(and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM
      H2DCFDA). PLD and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)
      oxidase were assessed with the inhibitors, dihydro-D-erythro-sphingosine
      (sphinganine) and diphenylene iodinium (DPI), respectively, and protein kinase C
      (PKC) effects were determined using chelerythrine chloride and calphostin C. PLD
      activity was measured by the transphosphatidylation assay. RESULTS: Ang II
      increased the CM-H2DCFDA fluorescence signal, derived predominantly from H2O2.
      Ang II-induced generation of DPI-inhibitable ROS was significantly enhanced in
      cells from hypertensives compared with normotensives (Emax = 72 +/- 2 versus 56.9
      +/- 1.8 fluorescence units, P< 0.01). PLD inhibition attenuated Ang II-induced
      ROS generation, with greater effects in the hypertensive group than the
      normotensive group (delta = 42 +/- 3.3 versus 21 +/- 2 units). PKC inhibition
      partially decreased Ang II-elicited signals. Ang II-stimulated PLD activity and
      DNA and protein synthesis were significantly greater in cells from hypertensives
      than normotensives. These effects were normalized by DPI and sphinganine.
      CONCLUSIONS: Our results suggest that in essential hypertension enhanced
      oxidative stress and augmented growth-promoting actions of Ang II are associated
      with increased activation of PLD-dependent pathways. These processes may
      contribute to vascular remodeling in hypertension.

PMID- 11446715
TI  - Inhibition of nitric oxide synthesis accentuates blood pressure elevation in
      hyperinsulinemic rats.
AB  - OBJECTIVES: To examine the role of endogenous nitric oxide (NO) in the
      pathogenesis of hypertension and insulin resistance in chronic hyperinsulinemic
      rats. METHODS: Sustained hyperinsulinemia was achieved by insulin infusion (21.5
      pmol/kg per min) via subcutaneous osmotic minipump for 6 weeks. NO synthase
      inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg per day) was
      given orally after 4 weeks of vehicle or insulin infusion. The systolic blood
      pressure (SBP) was measured under conscious state by an electrosphygmomanometer
      before and after drug treatments. RESULTS: Insulin infusion alone significantly
      increased SBP from 134 +/- 3 to 156 +/- 2 mmHg by week 4 and further to 158 +/- 3
      mmHg by week 6 of insulin infusion. The insulin-infused rats had markedly
      decreased insulin sensitivity, as reflected by an elevated steady-state plasma
      glucose level estimated by the insulin suppression test. There were no
      significant differences in plasma glucose and triglyceride levels between rats
      with and without insulin infusion. When hypertension had been established in rats
      receiving insulin infusion for 4 weeks, superimposed L-NAME on insulin infusion
      for additional 2 weeks further increased SBP by 18 +/- 2 mmHg (from 157 +/- 2 to
      175 +/- 2 mmHg). Plasma levels of NO metabolites (NOx) significantly decreased
      from 13.7 +/- 1.1 micromol/l during the control period to 6.1 +/- 0.6 micromol/l
      after 4 weeks of insulin infusion and further reduced to 4.1 +/- 0.5 micromol/l
      after combined infusion of L-NAME and insulin. L-NAME treatment alone for 2 weeks
      in control rats significantly increased SBP by 33 +/- 2 mmHg (from 133 +/- 2 to
      166 +/- 2 mmHg) and plasma insulin levels, as a consequence of insulin
      resistance. Despite marked increases in blood pressure due to infusion of insulin
      alone or in combination with L-NAME, the sodium balance, urinary sodium and water
      excretions, water intake and body weight gain of insulin/L-NAME-treated rats were
      not significantly different from rats without insulin infusion. CONCLUSIONS:
      Sustained hyperinsulinemia causes partial impairment of NO production that may
      contribute to the development of insulin resistance and hypertension. Additional
      inhibition of NO synthesis by L-NAME accentuates the blood pressure elevation and
      insulin resistance in hyperinsulinemic rats. Furthermore, a rightward shift of
      the renal arterial pressure-natriuretic function relationship occurred in this
      hypertensive model.

PMID- 11446716
TI  - Fibroblast Na+-Li+ countertransport rate is elevated in essential hypertension.
AB  - OBJECTIVES: Elevated erythrocyte Na+- Li+ countertransport (SLC) rates are
      commonly found in essential hypertension. We have recently shown that human skin
      fibroblasts functionally express a phloretin-sensitive Na+-H+ exchange (NHE)
      which may also be similar to erythrocyte SLC because of amiloride-insensitivity.
      DESIGN AND METHODS: We investigated whether elevations in fibroblast SLC parallel
      the known elevations in erythrocyte SLC and in cell NHE that characterize
      essential hypertension. RESULTS: Higher fibroblast SLC rates were found among
      hypertensive patients (n = 23, median 48.8 nmol Li+/ mg(protein) per min) than in
      19 normotensive individuals of similar age and sex (median 14.8 nmol
      Li+/mg(protein) per min, P= 0.0002). As expected, erythrocyte SLC was elevated in
      patients with hypertension (median 411 versus 329 micromol/l(cell) per h, P=
      0.0273), but was not quantitatively related to fibroblast SLC. Finally,
      fibroblast NHE exchange activity was higher in essential hypertension (median
      Vmax 14.2 versus 7.6 mmol H+/l(cell) per min, P= 0.002), but was unrelated to
      fibroblast SLC. CONCLUSIONS: These findings extend to human skin fibroblasts the
      notion of abnormal Li+ transport in essential hypertension, and appear to be in
      accordance with the hypothesis that fibroblast SLC may be independent of NHE.
      However, molecular studies will be required to understand whether distinct
      exchangers and/or regulation mechanisms underlie these dysregulations.

PMID- 11446717
TI  - Role of the renal nerves in the control of renin synthesis during different
      sodium intakes in the rat.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of the renal nerves in
      the regulation of renin synthesis in normotensive rats at different sodium
      balance. METHODS: Forty-eight male Sprague-Dawley rats were divided in six
      experimental groups, combining three diets at different NaCl content (normal
      0.4%, low 0.04% or high 4.0%), and the surgical, bilateral renal denervation or
      the sham procedure. After 7 days of dietary treatment, all rats were sacrificed
      and plasma renin activity (PRA) was measured. Renin messenger RNA (mRNA) levels
      in the renal cortex were determined by semiquantitative polymerase chain
      reaction. RESULTS: PRA was higher in animals fed the low sodium diet compared
      with those at standard diet, while it was lower in animals fed the high sodium
      diet. Renal denervation decreased PRA in normal and low sodium groups, while it
      did not alter the PRA values in the high sodium group. Renin gene expression
      significantly increased in rats fed with the low sodium diet compared with the
      standard diet group, and significantly decreased in rats fed the high sodium diet
      Renal denervation significantly reduced renin mRNA levels in rats receiving the
      low sodium diet, but did not produce any significant change in normal or high
      sodium groups. CONCLUSION: The activation of renin gene expression during sodium
      depletion in rats is dependent on the presence of the renal nerves, while the
      suppression of renin gene expression during a sodium load seems to be due to the
      macula densa mechanism alone.

PMID- 11446718
TI  - Effect of altering conditions of the sequence method on baroreflex sensitivity.
AB  - BACKGROUND: The sequence method is widely used as a simple, non-invasive measure
      of baroreflex sensitivity (BRS). This technique, originally described in
      anaesthetized cats, has been transferred virtually unchanged to humans, without
      evidence that the optimal values in cats are the same as those in patients with
      cardiovascular disease. OBJECTIVE: To study the effect of altering the components
      of the sequence method on the measured BRS in patients with chronic heart failure
      (CHF) and in normal individuals. METHODS: Eighty patients with CHF [aged 62 +/-
      12 years (mean +/- SD)] and 40 normal control individuals [aged 38 +/- 15 years
      (mean +/- SD)] underwent measurement of heart rate and non-invasive blood
      pressure. Altering only the shift between blood pressure and R-R interval and the
      required correlation coefficient of the regression line had no effect on the
      value of BRS, but had a significant effect on the number of valid sequences.
      Alteration of the blood pressure or R-R interval thresholds, however, affected
      not only the number of valid sequences, but also the value of BRS in both groups.
      In normal controls, agreement with the bolus phenylephrine method was improved by
      increasing the blood pressure threshold, although this led to a reduction in the
      number of valid sequences. In patients with CHF, agreement was optimized by
      decreasing both the blood pressure and R-R interval thresholds. This also had the
      effect of increasing the number of valid sequences. CONCLUSION: Changes should be
      made to this technique, to optimize its validity in conscious humans,
      particularly when applied to patients with attenuated BRS.

PMID- 11446719
TI  - Negative inotropic effect of bradykinin in porcine isolated atrial trabeculae:
      role of nitric oxide.
AB  - OBJECTIVES: To investigate whether bradykinin affects cardiac contractility
      independently of its effects on coronary flow and noradrenaline release, and
      whether such inotropic effects, if present, are mediated via nitric oxide (NO).
      METHODS: Right atrial trabeculae were obtained from 35 pigs, suspended in organ
      baths and attached to isometric transducers. Resting tension was set at
      approximately 750 mg and tissues were paced at 1.5 Hz. Tissue viability was
      checked by constructing a concentration response curve (CRC) to noradrenaline.
      Next, CRCs were constructed to bradykinin, either under baseline conditions or
      after pre-stimulation with the positive inotropic agent forskolin (1 or 10
      micromol/l), in the absence or presence of the bradykinin type 2 (B2) receptor
      antagonist D-Arg [Hyp3-Thi5, d-Tic7, Oic8]-bradykinin (Hoe 140) (1 micromol/l),
      the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) (100
      micromol/l) and/or the NO scavenger hydroxocobalamin (200 micromol/l). RESULTS:
      Bradykinin exerted a negative inotropic effect, both with and without forskolin
      pre-stimulation, reducing contractility by maximally 22 +/- 3.6% (mean +/- SEM)
      and 23 +/- 3.6%, respectively (pEC50 8.37 +/- 0.23 and 8.62 +/- 0.22,
      respectively). L-NAME reduced this effect in pre-stimulated, but not in
      unstimulated, trabeculae. Hoe 140 and hydroxocobalamin fully blocked the
      inotropic effect of bradykinin. CONCLUSIONS: Bradykinin induces a modest negative
      inotropic effect in porcine atrial trabeculae that is mediated via B2 receptors
      and NO. The inconsistent results obtained with L-NAME suggest that it depends on
      NO synthesized de novo and/or NO from storage sites.

PMID- 11446720
TI  - Bradykinin metabolism in the isolated perfused rabbit heart.
AB  - BACKGROUND: Bradykinin is a potent cardioprotective hormone, the beneficial role
      of which in vivo appears to be limited by its rapid metabolism. Inhibitors of
      peptidases that degrade endogenously formed bradykinin are themselves
      cardioprotective, presumably by increasing local bradykinin concentrations. As
      bradykinin-degrading peptidases are potential therapeutic targets, it is
      important to identify these enzymes in different animal models of cardiac
      function. OBJECTIVE: To determine the mechanism of bradykinin degradation in the
      coronary circulation of the rabbit, using an isolated perfused heart preparation.
      DESIGN AND METHODS: [3H]Bradykinin (16 nmol/l) was perfused as a bolus through
      the isolated rabbit heart in the presence and absence of specific peptidase
      inhibitors. The effluent was collected and the radiolabeled metabolites of
      [3H]bradykinin were separated by high performance liquid chromatography,
      identified, and quantified. RESULTS: [3H]Bradykinin was metabolized to the extent
      of 62 +/- 3% in a single passage through the rabbit coronary circulation at a
      physiological flow rate. The metabolites were identified as [3H]bradykinin(1-5)
      and [3H]bradykinin(1-7),accounting for 50 +/- 4 and 12 +/- 2% of the
      radioactivity, respectively. Co-perfusion with the angiotensin converting enzyme
      inhibitor, ramiprilat, completely blocked formation of these metabolites.
      CONCLUSIONS: Angiotensin-converting enzyme fully accounts for the metabolism of
      [3H]bradykinin in the rabbit coronary circulation. This result contrasts with
      data obtained using rat heart, which demonstrated a prominent role for
      aminopeptidase P in bradykinin metabolism in this species.

PMID- 11446721
TI  - Ambulatory heart rate is underestimated when measured by an ambulatory blood
      pressure device.
AB  - OBJECTIVE: To test the validity of ambulatory heart rate (HR) assessment with a
      cuff ambulatory blood pressure (ABP) monitor. DESIGN: Cross-instrument comparison
      of HR measured intermittently by a cuff ABP monitor (SpaceLabs, Redmond,
      Washington, USA), with HR derived from continuous electrocardiogram (ECG)
      recordings (1) in a controlled laboratory experiment and (2) during long-term
      recording in a true naturalistic setting. PARTICIPANTS: Six normotensive subjects
      participated in the laboratory study. A total of 109 male white-collar workers
      underwent ambulatory monitoring, of which 30 were mildly hypertensive. METHODS:
      Four different laboratory conditions (postures: lying, sitting, standing,
      walking), repeated twice, were used to assess the short-term effects of cuff
      inflation on the HR. To test the actual ambulatory validity, participants
      simultaneously wore a continuous HR recorder and the ABP monitor from early
      morning to late evening on 2 workdays and one non-workday. Diary and vertical
      accelerometery information was used to obtain periods of fixed posture and
      (physical) activity across which HR from both devices was compared. RESULTS:
      Laboratory results showed that the ABP device reliably detected HR during blood
      pressure measurement, but that this HR was systematically lower than the HR
      directly before and after the blood pressure measurement. The ambulatory study
      confirmed this systematic underestimation of the ongoing HR, but additionally
      showed that its amount increased when subjects went from sitting to standing to
      light physical activity (2.9; 4.3 and 9.1 bpm (beats/min), respectively). In
      spite of this activity-dependent underestimation of HR, the correlation of
      continuous ECG and intermittent ABP-derived HR was high (median r= 0.81). Also,
      underestimation was not different for normotensives and mild hypertensives.
      CONCLUSIONS: A direct effect of cuff inflation leads to the underestimation of
      ongoing HR during cuff-based ABP measurement. Additional underestimation of HR
      occurs during periods with physical activity, probably due to behavioural
      freezing during blood pressure measurements. HR underestimation was not affected
      by hypertensive state. When its limitations are taken into account, ABP-derived
      ambulatory HR can be considered a reliable and valid measure.

PMID- 11446722
TI  - Renomedullary interstitial cell lipid droplet content is increased in
      spontaneously hypertensive rats and by low salt diet.
AB  - OBJECTIVE: To compare the volumes of renomedullary interstitial cell (RMIC) lipid
      droplets (putative source of vasodepressor substance) in spontaneously
      hypertensive (SHR) and Wistar-Kyoto (WKY) rats on high and low salt diets as an
      indication of whether the renomedullary vasodepressor system of the SHR is
      defective. METHODS: Ten-week-old male SHR and WKY rats received a low (0.05% w/w)
      or high salt (5.0%) diet for 21 days. Conscious mean arterial pressure (MAP) was
      measured and the renal papilla perfusion fixed with a high osmolarity fixative.
      Using electron microscopic stereological techniques, the volume density of lipid
      in RMIC (VVLipid,RMIC) and the total volumes of lipid (VLipid) and RMIC (VRMIC)
      in papilla were measured. RESULTS: MAP of SHR (high 155 +/- 3 mmHg; low 151 +/- 3
      mmHg) was significantly greater than WKY rats (high 126 +/- 2 mmHg; low 129 +/- 2
      mmHg; P< 0.001), however salt diet had no significant effect on MAP. The VLipid
      of rats on the low salt diet was approximately 2.5 times greater than in rats on
      the high salt diet (P < 0.01). SHR had significantly greater VLipid than WKY rats
      irrespective of salt diet (P< 0.05; SHR-low 0.245 +/- 0.031 mm3, SHR-high 0.093
      +/- 0.007 mm3; WKY-low 0.126 +/- 0.032 mm3, WKY-high 0.051 +/- 0.020 mm3).
      Similar differences were seen for VVLipid,RMIC, however VRMIC was not different
      between rat strains or salt diet groups. CONCLUSIONS: SHR and WKY rats responded
      similarly to the altered salt diets, and SHR demonstrated greater volumes of
      stored RMIC lipid droplets irrespective of the level of salt intake. These
      results indicate that SHR hypertension is not due to a deficiency in the amount
      of lipid droplets, the putative source of the renomedullary vasodepressor
      substance and that the renomedullary vasodepressor system of the SHR is capable
      of responding normally to the physiological stimulus of altered salt intake.

PMID- 11446723
TI  - High and low serum potassium associated with cardiovascular events in diuretic
      treated patients.
AB  - OBJECTIVE: To determine the relationship of moderately high and low
      concentrations of serum potassium with cardiovascular disease events among
      treated hypertensive patients. DESIGN: An observational cohort study with
      prospectively collected data. SETTING: A worksite treatment program for mild
      hypertension. PATIENTS: All program participants with baseline and at least one
      annual follow-up measure of serum potassium; 7,653 individuals with 6.7 years
      mean follow-up met these criteria. MAIN OUTCOME MEASURES: Outcome events were
      admissions to hospital because of cardiovascular disease, and deaths. The
      research question regarding serum potassium categories was formulated after data
      collection. The serum potassium concentration (mean +/- 2SD) of the study
      population was used to define low (3.0-3.5 mmol/l), high (5.1-5.9 mmol/l) and
      middle (3.6-5.0 mmol/l) categories. RESULTS: Individuals with low (n = 146) and
      high (n = 226) serum potassium had significantly greater risk for cardiovascular
      disease events than those in the middle category (n = 7,281). Multivariate
      adjusted hazard ratios from Cox models were 2.6 [95% confidence intervals (CI)
      1.5-4.4] for the low potassium group and 1.7 (95% CI 1.0-2.7) for the high
      potassium group, with the middle group as reference. Among 1,679 individuals who
      regularly took diuretics, hazard ratios were 4.3 (95% CI 2.4-7.9) for the low
      potassium group and 6.7 (95% CI 2.8-15.9) for the high group. Neither low nor
      high potassium was significantly associated with outcome events for those not
      regularly using diuretics. CONCLUSIONS: These data confirm an association of mild
      hypokalemia with increased cardiovascular events among diuretic-treated
      hypertensive patients. In addition, we have found a similar increased
      cardiovascular risk associated with modest hyperkalemia among these patients.
      Whether modification of these serum potassium concentrations would alter that
      risk remains to be determined.

PMID- 11446724
TI  - Effect of potassium supplementation on blood pressure in Chinese: a randomized,
      placebo-controlled trial.
AB  - OBJECTIVE: To examine the effect of potassium supplementation on blood pressure
      (BP) in a Chinese population who consume a habitual high sodium and low potassium
      diet. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING:
      Community sample from Beijing, China. PARTICIPANTS: A total of 150 men and women
      aged 35-64 years with an initial systolic BP 130-159 mmHg and/or diastolic BP 80
      94 mmHg. INTERVENTIONS: Participants were randomly assigned to take 60 mmol
      potassium chloride supplement or placebo for 12 weeks. MAIN OUTCOME MEASURE(S):
      BP measurements were obtained at baseline, and at 6 weeks and 12 weeks during the
      trial, using random-zero sphygmomanometers. RESULTS: The average baseline urinary
      excretion of sodium and potassium was 182 mmol/24 h and 36 mmol/24 h. Baseline BP
      and other measured variables were similar between the potassium supplementation
      and placebo groups. In the active compared to the placebo treatment group, the
      urinary excretion of potassium was significantly increased by 20.6 mmol/24 h (P<
      0.001) during 12 weeks of intervention. Compared to placebo, active treatment was
      associated with a significant reduction in systolic BP (-5.00 mmHg, 95% CI: -2.13
      to -7.88 mmHg, P < 0.001) but not diastolic BP (-0.63 mmHg, 95% CI: -2.49 to1.23
      mmHg, P = 0.51) during 12-week intervention. CONCLUSION: These data indicate that
      moderate potassium supplementation resulted in a substantial reduction in
      systolic BP. Our findings suggest that increased potassium intake may play an
      important role in the prevention and treatment of hypertension in China.

PMID- 11446725
TI  - Inequalities in the treatment and control of hypertension: age, social isolation
      and lifestyle are more important than economic circumstances.
AB  - OBJECTIVE: To describe socio-economic variations in the treatment and control of
      hypertension in England. DESIGN: Population based survey. SUBJECTS: Hypertensives
      numbering 5019, identified in the Health Survey for England for 1993-1994.
      OUTCOME: Drug treatment and control of hypertension. RESULTS: A total of
      1119/2208 (50.7%) hypertensive men, and 1620/2811 (57.6%) hypertensive women,
      were receiving anti-hypertensive medication. For men, the likelihood of receiving
      treatment increased with age, widowerhood or divorce, a family history of heart
      disease, low social support and increasing weight, but was decreased for men who
      lived alone, owned their own house, smoked or drank heavily. For women, obesity,
      a family history of heart disease and low social support increased their chance
      of treatment. A total of 534/1119 (47.7%) men, and 816/1620 (50.4%) of women on
      treatment, had their hypertension controlled to below 160/90 mmHg. Lack of
      control was more commonly due to isolated systolic hypertension rather than
      diastolic hypertension. Increasing age and smoking were associated with poorer
      control. Men who lived alone and had low social support were less likely to have
      their hypertension controlled, while those with a family history of heart disease
      were more likely to be controlled. DISCUSSION: We found little evidence for socio
      economic or geographic differences in the management of hypertension. Variations
      in treatment rates can be explained by variations in use of primary care and
      opportunistic screening. Control was poorest among older people who are at the
      highest risk of cardiovascular events. Socially isolated men and smokers were
      less likely to be treated or controlled, and need to be targeted by future
      programmes to detect and treat hypertension.

PMID- 11446726
TI  - Functional gene testing of the Glu298Asp polymorphism of the endothelial nitric
      oxide synthase.

PMID- 11446727
TI  - Clinical approaches to vaccination in oncology.
AB  - Immunotherapy of cancer is still in the early stages of development although
      almost a century has passed since initial attempts were made to stimulate the
      immune system in order to destroy malignant cells. Historically, a variety of
      specific and non-specific immunostimulatory strategies have been administered
      with only modest clinical success. However, recent advances in tumour immunology,
      most notably the identification of new tumour antigens and the better
      understanding of antigen processing and presentation to avoid or break immune
      tolerance, have paved the way for the development of a variety of novel and
      specific vaccine approaches. The most important and widely used are whole-cell
      vaccines, dendritic-cell-based immunotherapy and peptide vaccines. The first wave
      of clinical trials has revealed that, in general, such vaccination strategies are
      safe. However, clear examples of clinical responses, especially in conjunction
      with vaccine-induced immune responses, are still rare. Most clinical trials are
      too small to allow for comments on the efficacy, and the cohort of patients
      studied is too heterogeneous with regard to immune status. Therefore,
      standardised techniques for the accurate assessment of the individual immune
      phenotype before and during the trial are needed to allow for the identification
      of the sub-group of patients who will respond favourably to treatment. The
      precise definition of immune parameters in these patients will then lead the way
      for optimised treatment procedures that might even be beneficial for a larger
      group of cancer patients.

PMID- 11446728
TI  - Consolidation treatment with autologous peripheral blood progenitor cell
      transplantation in acute myeloid leukemia: a single center experience.
AB  - Several trials have suggested that intensive post-remission therapy may prolong
      the duration of complete remission (CR) in acute myeloid leukemia (AML). The
      purpose of this study was to evaluate the feasibility and the efficacy of high
      dose cytarabine (HiDAC) consolidation chemotherapy followed by high-dose therapy
      and autologous infusion of peripheral blood progenitor cells (PBPC) mobilized by
      G-CSF in adult patients with AML in first CR. Fifteen consecutive AML patients
      underwent HiDAC consolidation chemotherapy, used as a method of in vivo purging,
      followed by G-CSF for the purpose of autologous PBPC collection. Eleven patients
      collected a median of 6.9x10(8)/kg peripheral blood mononuclear cells (MNC)
      (range 2.9-23) and a median of 6.67x10(6)/kg CD34+ cells (range 1.8-33.5) with a
      median of two aphereses (range 1-3). Two patients did not mobilize and two
      obtained an inadequate number of progenitor cells. The 11 patients with adequate
      collections received myeloablative chemotherapy followed by the infusion of PBPC.
      The median number of days to recover neutrophils and platelets was 12 and 13,
      respectively. After a median follow-up of 28.7 months (range 17.2-43.4), five out
      of 11 patients who underwent PBPC transplantation are still in CR, five have died
      in first relapse and one is alive in CR after relapse treated with salvage
      therapy and second PBPC infusion. These results demonstrate that HiDAC
      consolidation chemotherapy followed by autologous PBPC transplantation is a
      feasible procedure with minimal toxicity. Randomized studies should be performed
      to evaluate whether this form of consolidation may produce a significant
      improvement in leukemia-free survival.

PMID- 11446729
TI  - Survival analysis and AML development in patients with de novo myelodysplastic
      syndromes: comparison of six different prognostic scoring systems.
AB  - A number of prognostic scoring systems for patients with myelodysplastic
      syndromes (MDS) have been introduced in the past. In the present study, survival
      and AML evolution were analyzed retrospectively in a total of 180 patients with
      de novo MDS (observation period: 1989-1999; median age: 71; range 27-93; f/m
      ratio: 1/1.2). Diagnoses were established according to FAB criteria (RARS, n=37;
      RA, n=53; RAEB, n=50; RAEB-t, n=19; CMML, n=21). Six different multiparameter
      scoring systems (the Mufti, Aul, Sanz, Morel, and Toyama scores, and the
      international prognostic scoring system [IPSS]) were applied. The Aul, Sanz, and
      Mufti scores were applied to all 180 patients, Morel and Toyama scores to 109
      patients, and the IPSS to 102. As assessed by multivariate analysis, the
      percentage of bm-blasts, hemoglobin, platelet count, neutrophil count, LDH, and
      karyotype were found to be independent single variables for survival, and bm
      blasts, neutrophil count, platelet count, and karyotype for AML evolution. All
      prognostic scoring systems applied appeared to be highly predictive for survival
      and AML development (P<0.001). The highest predictive values were found for the
      Aul, Sanz, and Toyama scores for overall survival, and the IPSS, Toyama, and
      Morel scores for AML-free survival. In summary, our data show that scoring
      systems are useful for predicting overall and AML-free survival in patients with
      MDS. Karyotype-based multiparameter systems appear to be particularly effective
      in defining MDS patients who are at high risk of transforming to leukemia.

PMID- 11446730
TI  - Human peripheral blood mononuclear cells require factor X and platelets for
      expression of prothrombinase activity in response to bacterial
      lipopolysaccharide.
AB  - We investigated whether human peripheral blood mononuclear cells (PBMC) express
      prothrombinase following stimulation with bacterial lipopolysaccharide (LPS). LPS
      stimulated PBMC devoid of contaminating platelets failed to activate prothrombin
      directly. Addition of platelets did not result in expression of prothrombinase in
      the absence of factor X whereas the combination of platelets and factor X
      resulted in strong prothrombinase activity on LPS-activated cells. The induced
      prothrombinase was dependent on tissue factor, as the activity was completely
      inhibited by an anti-tissue factor antibody. Our data suggest that
      platelet/monocyte cooperation is important in the generation of prothrombinase
      activity in response to endotoxin.

PMID- 11446731
TI  - Requirement of thrombopoietin-induced activation of ERK for megakaryocyte
      differentiation and of p38 for erythroid differentiation.
AB  - Thrombopoietin (TPO) plays a critical role not only in proliferation and
      differentiation of megakaryocytes but also in erythroid differentiation. We have
      investigated whether the different pathway of mitogen-activated protein kinase
      (MAPK) after TPO stimulation may discriminate megakaryocyte and erythroid
      differentiation. In this study, we have used human CD34+ hematopoietic progenitor
      cells (HPCs) from cord blood (CB) in serum-free liquid culture supplemented with
      TPO, to compare the respective effects of specific inhibitors of MAPK kinase
      (MEK) (PD98059) and p38 MAP kinase (p38) (SB203580) on megakaryocyte and
      erythroid development. PD98059, but not SB203580, significantly suppressed TPO
      induced megakaryocyte differentiation when examined by the expression of CD41 and
      polyploidy assay. In the presence of SB203580, CD34+/CD36+ erythroid progenitors
      clearly decreased, whereas they increased when cultured with PD98059. These
      results indicate that activation of extracellular-signal-regulated kinase (ERK)
      is required for TPO-induced megakaryocyte differentiation and that p38 is
      required for TPO-induced erythroid differentiation.

PMID- 11446732
TI  - Molecular characterization of the ERGIC-53 gene in two Japanese patients with
      combined factor V-factor VIII deficiency.
AB  - Combined deficiency of factor V and factor VIII is a distinct clinical entity and
      is an autosomal recessive disorder. Recently identification of the gene, the
      endoplasmic reticulum-Golgi intermediate compartment (ERGIC-53), responsible for
      combined factor V-factor VIII deficiency and mutations of the ERGIC-53 gene in
      affected patients have been reported. In this report we analyzed two Japanese
      patients with combined factor V-factor VIII deficiency by genomic polymerase
      chain reaction and sequencing analysis. In one patient we found a point mutation
      of C to T at nucleotide 604 in exon 5, resulting in a transition of arginine to
      stop codon, which was reported in previous reports. The DdeI digestion study
      demonstrated that this patient is homozygous for this nonsense mutation. In the
      other patient we found no mutation in the ERGIC-53 gene in analysis of the entire
      coding region and the intron/exon junctions, which is also consistent with the
      previous reports, suggesting the possibility of defects at other genetic loci.

PMID- 11446733
TI  - Anemia: an indicator for malnutrition in the elderly.
AB  - The prevalence of anemia increases with age and is frequently multifactorial. We
      postulated that malnutrition contributes to anemia in the elderly and is
      underdiagnosed. Our objective was to analyze the prevalence of anemia and its
      association with nutritional status in a hospitalized geriatric population.
      Included in this retrospective cohort study were 186 consecutive patients
      admitted in 1997 to a geriatric unit of a university hospital. We compared
      hematological and chemical blood tests routinely performed upon admission in
      patients with anemia (hemoglobin <120 g/l) and without anemia (hemoglobin > or =
      120 g/l). Using these admission parameters, we defined a multiparameter score of
      malnutrition by low lymphocyte counts, decreased values of albumin, cholesterol,
      transferrin, cholinesterase, and zinc, iron deficiency by low transferrin
      saturation and normal C-reactive protein, and inflammation by increased C
      reactive protein and high transferrin saturation. Of the 186 patients, 82 (44%)
      met the criteria for anemia on admission. In univariate analysis, patients with
      anemia differed significantly from patients with normal hemoglobin exhibiting
      lower serum values of albumin, iron, transferrin, cholesterol, cholinesterase,
      zinc, transferrin saturation, and lymphocyte count and higher C-reactive protein
      levels. Using a multiparameter score, anemia correlated significantly with
      parameters of malnutrition (P=0.0001) but not with iron deficiency (P=0.5) or
      with inflammation (P=0.08). In a multivariate logistic regression model, anemia
      was significantly associated with serum albumin (RR: 1.138; 95% CI: 1.056-1.227;
      P=0.0007), cholinesterase (RR: 1.387; 95% CI 1.122-1.714; P=0.0025), and
      transferrin saturation (RR: 1.05; 95% CI: 1.012-1.09; P=0.009). We conclude that
      malnutrition may play an important etiologic role in anemia in the elderly.

PMID- 11446734
TI  - Pure red cell aplasia after ABO-incompatible allogeneic stem cell transplantation
      in severe aplastic anemia with response to steroids: a case report and literature
      review.
AB  - Pure red cell aplasia (PRCA) is a rare complication after ABO-incompatible
      allogeneic stem cell transplantation, but its mechanism is still unknown. Here we
      report on a patient with severe aplastic anemia who developed PRCA after HLA
      identical but major ABO-mismatched peripheral blood stem cell transplantation.
      Erythroid engraftment was successful with primary steroid treatment. We concluded
      that an adequate dose of steroids can be the first line of therapy for PRCA after
      ABO-mismatched allogeneic stem cell transplantation.

PMID- 11446735
TI  - Complex karyotype and absence of mutation in the c-kit receptor in aggressive
      mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage.
AB  - Aggressive mastocytosis is a form of systemic mast cell disease (SMCD)
      characterized by organ infiltration, bone lesions. eosinophilia and
      lymphadenopathies. Here we report a patient with unusual clinical features,
      namely osteolysis without other bone lesions commonly found in SMCD, major
      eosinophilia and cerebral infarction. The mast cells exhibited a classical
      immunophenotype (CD2+, CD9+, CD13+, CD25+, CD35+, CD45c+ and CD117+). Cytogenetic
      investigation showed novel complex aberrations, and clonal evolution was
      correlated with clinical progression. The screening for recurrent point mutations
      affecting the c-kit gene was negative. Mainly, the ASP816VAL substitution was not
      detected in our patient. Treatment with steroids and interferon was only
      temporarily effective.

PMID- 11446736
TI  - Pulmonary artery hypertension during interferon-alpha therapy for chronic
      myelogenous leukemia.
AB  - In the conventionally treated group of patients with chronic myelogenous leukemia
      (CML) the prognosis has been significantly improved by interferon-alpha (IFN
      alpha). Several side effects in association with IFN-alpha treatment have been
      reported. Here we present the first case of a CML patient with reversible
      pulmonary artery hypertension (PAH) during IFN-alpha therapy. The patient
      received IFN-alpha-2b (up to 10 million U/day) for 6 months until he started to
      complain of dyspnea on exertion and an afebrile non-productive cough. An
      echocardiography and right heart catheterization showed signs of right heart
      failure with PAH (80 mmHg). A reduced carbon monoxide diffusion capacity and
      partial respiratory insufficiency were noted. Inflammatory markers were not
      elevated and pulmonary infiltrates could not be detected. Respiratory infections,
      thromboembolic causes or autoimmune diseases were carefully ruled out. IFN-alpha
      was suspected as causative agent, because experimental investigations in sheep
      showed that IFN-alpha can stimulate the thromboxane cascade which resulted in
      transient PAH. A reduced pulmonary diffusion capacity had been observed secondary
      to PAH. After discontinuation of IFN-alpha, our patient's clinical status
      improved rapidly. After 6 months the pulmonary artery pressure had returned to
      near normal values (35 mmHg) and the pulmonary diffusion capacity was normal. It
      took one year until the electrocardiogram reverted to the pre-IFN-alpha pattern.
      PAH should be included in the differential diagnosis of patients treated with IFN
      alpha who complain of exertional dyspnea in the absence of inflammatory signs.

PMID- 11446737
TI  - Primary lymphoma of the conjunctiva--a rare manifestation of indolent non
      Hodgkin's lymphoma.
AB  - Lymphoid tumours of the conjunctiva are extremely rare. Such tumours can appear
      as an isolated neoplasm or as part of a systemic disease. We describe the
      clinical and histopathologic findings of a patient with bilateral conjunctival
      lymphoma who presented with a 5-year history of chronic conjunctivitis. After
      clinical staging, including (1) thoracic and abdominal computerised tomography
      scans, (2) magnetic resonance tomography of the brain and orbita, (3) fibre-optic
      gastrointestinoscopy, (4) colonoscopy and (5) bone marrow biopsy,.no other foci
      of the lymphoma were found. The patient received radiation therapy and achieved
      complete remission. We conclude that conjunctival lymphoma should be included in
      the differential diagnoses of chronic conjunctivitis. Persisting signs and
      symptoms of conjunctivitis not responding to standard treatment should prompt
      biopsy.

PMID- 11446738
TI  - Acute tumor lysis syndrome induced by high-dose corticosteroids in a patient with
      chronic lymphatic leukemia.
AB  - Acute tumor lysis syndrome (TLS) has been reported in hematological malignancies,
      such as aggressive non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and
      rarely, in other malignancies (solid tumors) in association with the
      administration of cytotoxic therapy. We report a case of a patient with chronic
      lymphatic leukemia (CLL) who developed autoimmune hemolytic anemia treated by
      high dose corticosteroids and, following this treatment, developed acute tumor
      lysis syndrome. Only one similar case has been reported recently. Clinicians
      should be aware that corticosteroids alone may produce this potentially life
      threatening complication.

PMID- 11446739
TI  - Intravascular large B-cell lymphoma or intravascular lymphomatosis: report of a
      case diagnosed by testicle biopsy.
AB  - Intravascular large B-cell lymphoma or intravascular lymphomatosis (IVL) is an
      extremely rare form of non-Hodgkin's lymphoma. The most common clinical sign is
      fever of unknown origin (FUO). Histologically, there is proliferation of
      malignant lymphoid cells within vascular lumina. Cytologically, the cells have
      features similar to those found in classical large cell lymphoma. Examination of
      pulmonary artery blood showed the presence of this abnormal population in our
      patient; to the best of our knowledge there are only four other. reports of
      detection of circulating tumor cells in IVL. The outcome is very poor. The
      diagnosis is most frequently made after biopsy of skin or brain but is often
      established post mortem. We present what is--to our knowledge--the first reported
      case of IVL diagnosed after biopsy of a testicle. In the event of FUO and
      suspicion of a malignancy, IVL--although very rare--should be one of the
      differential diagnoses.

PMID- 11446740
TI  - Role of C chemokine lymphotactin in mediating recruitment of antigen-specific
      CD62L(lo) cells in vitro and in vivo.
AB  - In this study we investigated whether T cells expressing high or low levels of
      CD62L were differentially susceptible to the T cell chemokine lymphotactin. We
      found that lymphotactin induced preferential migration of antigen-specific
      (CD62L(lo)) T cells over the nonspecific (CD62L(hi)) T cells in vitro and in
      vivo. The differing migratory abilities correlated with higher levels of mRNA
      encoding the lymphotactin receptor (XCR1) on the CD62L(lo) cells compared to the
      CD62L(hi) cells. Thus, we have identified a coupling mechanism between the
      activation of T cells and acquisition of new homing properties, in this case
      conferred by XCR1 expression. These data confirm that at least one function of
      lymphotactin includes mediating the recruitment of recently activated antigen
      specific T cells.

PMID- 11446741
TI  - Feverfew extracts and the sesquiterpene lactone parthenolide inhibit
      intercellular adhesion molecule-1 expression in human synovial fibroblasts.
AB  - Previous studies have shown that extracts of the aromatic herb feverfew
      (Tanacetum parthenium) and one of its bioactive components, parthenolide, have
      anti-inflammatory properties in vivo and in vitro. We examined both crude
      feverfew extracts and purified parthenolide for their ability to modulate
      adhesion molecule expression in human synovial fibroblasts. Pretreatment of
      synovial fibroblasts with either feverfew extracts or purified parthenolide could
      inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) induced by
      the cytokines IL-1 (up to 95% suppression), TNF-alpha (up to 93% suppression),
      and, less strongly, interferon-gamma (up to 39% suppression). Inhibition of ICAM
      1 was dose and time dependent; as little as a 30-min pretreatment with feverfew
      resulted in inhibition of ICAM-1. The decrease in ICAM-1 expression was
      accompanied by a decrease in T-cell adhesion to the treated fibroblasts. Other
      herbal extracts with reported anti-inflammatory effects were similarly tested and
      did not decrease ICAM-1 expression. The modulation of adhesion molecule
      expression may be an additional mechanism by which feverfew mediates anti
      inflammatory effects.

PMID- 11446742
TI  - Mutation of the invariant chain transmembrane region inhibits II degradation,
      prolongs association with MHC class II, and selectively disrupts antigen
      presentation.
AB  - The invariant chain (Ii) is a key player in regulating the MHC Class II antigen
      presentation pathway. Here we used site-directed mutagenesis to identify
      functionally important regions of the invariant chain in regulating antigen
      presentation function in transfected cells. Mutation of Ii residues 42-53 caused
      a defect in the presentation of the ovalbumin 247-265/A(k) epitope, but not in
      the inhibition of presentation of two hen egg lysozyme epitopes, HEL34-45/A(k)
      and HEL74-88/A(b), from endogenously expressed antigens. The mutation did not
      prevent ER translocation, trimerization, or association with MHC Class II
      molecules and had no obvious effect on endosomal targeting of Ii. It did,
      however, increase the half-life of the invariant chain, suggesting that sequences
      in this region influence the degradation of the invariant chain and as a
      consequence its function in antigen presentation.

PMID- 11446743
TI  - Idiotype and antigen-specific T cell responses in mice on immunization with
      antigen, antibody, and anti-idiotypic antibody.
AB  - Idiotypic determinants of immunoglobulin molecules can evoke both CD4(+) and
      CD8(+) T responses and exist not only as the integral components of a bona fide
      antigen binding receptor but also as distinct molecular entities in the processed
      forms on the cell surface of B lymphocytes. The present work provides
      experimental evidence for the concept that regulation of memory B cell
      populations can be achieved through the presentation of idiotypic and anti
      idiotypic determinants to helper and cytotoxic cell. The potential of B cells to
      present antigens to helper and cytotoxic T cells through class II and class I MHC
      suggests a mechanism by which both B and T cell homeostasis can be maintained. We
      provide evidence for the generation of idiotype- and antigen-specific Th and Tc
      cells upon immunization of syngenic mice with antigen or idiotypic antibody (Ab1)
      or anti-idiotypic antibody (Ab2). The selective activation and proliferation of
      the antigen-specific Th and Tc cells mediated by idiotypic stimulation observed
      in these experiments suggests a B-cell-driven mechanism for the maintenance of
      antigen-specific T cell memory in the absence of antigenic stimulation, under
      certain conditions.

PMID- 11446744
TI  - Codelivery of DNA coding for the soluble form of CD86 results in the down
      regulation of the immune response to DNA vaccines.
AB  - The costimulatory pathway that includes CD80, CD86, CD28, and CTLA-4 plays a key
      role in regulating T cell activation and tolerance and is a promising therapeutic
      target. We have studied the possibility of down-regulating the immune response to
      DNA vaccine by codelivery of a plasmid coding for the extracellular domains of
      CD86 (pDelta86). We found that DeltaCD86 was able to inhibit the engagement of
      FcCTLA-4 but not of FcCD28 to CD80 and CD86 expressed on COS cells.
      Coadministration of plasmid pDelta86 encoding for the extracellular domains of
      CD86 along with a plasmid encoding for the glycoprotein D (pgD) of herpes simplex
      virus-2 (a membrane-bound protein) by the im route in mice resulted in a strong
      inhibition of the cell-mediated immune response in the spleen and in draining
      lymph nodes. In addition, when pDelta86 was coadministered together with a
      plasmid encoding for the ovalbumin (pOVA) (a soluble protein), a strong
      inhibition of the cell-mediated immune response was observed in draining lymph
      nodes and only a partial inhibition was found in the spleen. Furthermore, only a
      partial down-regulation of the humoral immune response was observed. The
      mechanism involved could be a preferential engagement of DeltaCD86 to CTLA-4
      leading to the transmission of a negative signal to T lymphocytes.

PMID- 11446745
TI  - Regulation of granulocyte-macrophage colony-stimulating factor in human retinal
      pigment epithelial cells by IL-1beta and IFN-gamma.
AB  - GM-CSF production by RPE cells, which form part of the blood-retina barrier, is
      upregulated by IL-1beta and this increase can be reversed by IFN-gamma. IL-1beta
      up-regulation is not dependent on PKC but the PKC activator PMA induces low
      levels of GM-CSF production and acts synergistically with IL-1beta to further
      increase GM-CSF. Although A23187 and ionomycin stimulated low levels of GM-CSF
      production, the IL-1beta pathway was cyclosporin A insensitive and did not
      interact with the calcium pathway. IL-1beta-stimulated GM-CSF mRNA expression and
      production was strongly dependent on NF-kappaB. IFN-gamma inhibition of the GM
      CSF response to IL-1beta acted via NF-kappaB, reducing the translocation of NF
      kappaB to the nuclei of RPE cells treated with IL-1beta and IFN-gamma. The
      results show that IFN-gamma down-regulation acts either directly on NF-kappaB or
      its activation or by blockade of a pathway upstream of NF-kappaB. However, any
      such blockade does not involve PKC or intracellular calcium.

PMID- 11446746
TI  - Bone marrow-derived macrophages express functional CGRP receptors and respond to
      CGRP by increasing transcription of c-fos and IL-6 mRNA.
AB  - Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with
      inflammatory and immunoregulatory properties. CGRP inhibits IL-7 responses by B
      cell precursors by direct and indirect mechanisms. We recently found that CGRP
      induces IL-6 and TNF-alpha in long-term bone marrow cultures and that IL-6 and
      TNF-alpha also inhibit IL-7 responses. Because these are heterogeneous cultures,
      it was not clear which cells produced IL-6 and TNF-alpha. To determine whether
      bone marrow-derived macrophages (BMDM) were the source, we did studies to
      determine whether BMDMs express mRNAs for CGRP receptors and whether CGRP induces
      c-fos, IL-6, and TNF-alpha mRNA. We found that BMDMs express mRNAs for CRLR and
      RAMP1, the minimal components for CGRP receptors. CGRP also stimulated dose- and
      time-dependent increases in c-fos and IL-6. In contrast, CGRP did not induce TNF
      alpha in BMDMs. These results suggest that BMDMs are a source of CGRP-induced IL
      6 in bone marrow.

PMID- 11446747
TI  - Hypoestoxide, a novel anti-inflammatory natural diterpene, inhibits the activity
      of IkappaB kinase.
AB  - Most inflammatory agents activate nuclear factor-kappaB (NF-kappaB), resulting in
      induction of genes coding for cytokines, chemokines, and enzymes involved in
      amplification and perpetuation of inflammation. Hypoestoxide (a bicyclo [9,3,1]
      pentadecane) is a diterpene from Hypoestes rosea, a tropical shrub in the family
      Acanthacea, several members of which are used in folk medicine in Nigeria. Here,
      we demonstrate that hypoestoxide (HE) abrogates the production of pro
      inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in lipopolysaccharide
      (LPS)-activated normal human peripheral blood mononuclear cells. Moreover, HE
      inhibits the production of nitric oxide (NO) by IL-1beta- or IL-17-stimulated
      normal human chondrocytes. In vivo, oral administration of HE to mice
      significantly ameliorated hind paw edema induced by antibodies to type II
      collagen plus LPS. Furthermore, topical administration of HE to mice also
      significantly inhibited phorbol ester-induced ear inflammation. The anti
      inflammatory activity of HE may be due in part to its ability to inhibit NF
      kappaB activation through direct inhibition of IkappaB kinase (IKK) activity.
      Thus, HE could be useful in treating various inflammatory diseases and may
      represent a prototype of a novel class of IKK inhibitors.

PMID- 11446748
TI  - Oncological radiology.

PMID- 11446749
TI  - Computed tomography angiography in the investigation of carotid stenosis.
AB  - The assessment of carotid atherosclerotic disease is an essential pre-requisite
      for determining a patients suitability for carotid endarterectomy to prevent
      ischaemic stroke. Catheter angiography is regarded as the most accurate
      investigative tool for this purpose. However, with its finite morbidity and
      invasiveness, there is an increasing reliance upon non-invasive methods to
      accurately assess carotid disease. We present a review of the technique and
      applications of computed tomography angiography.

PMID- 11446750
TI  - Mycobacterial infections: still a millennium bug--the imaging features of
      mycobacterial infections.
AB  - Mycobacterial infection is re-emerging as a major health care concern. Although
      Mycobacterium tuberculosis(MTB) is still the most important pathogen, atypical
      mycobacterium (AMB) infections are becoming increasingly common. We present a
      pictorial review of the imaging features of these infections in the chest,
      abdomen, brain and musculoskeletal system. Imaging similarities and differences
      between the normal and the immunocompromised host will be highlighted.

PMID- 11446751
TI  - Value of subtraction technique in Gd-DTPA-enhanced magnetic resonance angiography
      of the thoracic aorta.
AB  - AIM: To assess routine image subtraction in 3D gadopentate dimeglumine (Gd-DTPA)
      enhanced magnetic resonance (MR) angiography of the thoracic aorta. MATERIALS AND
      METHODS: This was a prospective study of 22 consecutive patients referred for
      magnetic resonance imaging (MRI) of the thoracic aorta. All patients had 3D MR
      aortography (TR/TE/FA; 5/2 ms/25 degrees ) performed before and after bolus
      intravenous injection of Gd-DTPA. The Gd-DTPA enhanced and unenhanced data sets
      were subtracted and maximum intensity projections (MIP) projections of the
      thoracic aorta were performed. The standard unsubtracted MIP images were
      initially evaluated. These were then reviewed together with the subtracted images
      to assess for additional diagnostic information. Signal to noise ratios (SNR) and
      contrast to noise ratios (CNR) were measured. RESULTS: In four cases there was
      mild image degradation due to patient movement. In no case did subtraction alter
      the diagnosis. The mean SNR in the unsubtracted MIP images was 10.8 +/- 4.0
      (median 11.1) and on the subtracted images was 21.2 +/- 9.9 (median 20.7;P <
      0.0001). The mean aorta-to-mediastinal fat CNR was 3.9 +/- 2.8 (median 3.9) on
      the unsubtracted images and 15.0 +/- 10.6 (median 13) on the subtracted images (P
      < 0.0001). The mean aorta-to-vertebral body CNR was 5.2 +/- 3.1 (median 4.4) on
      the unsubtracted images and 15.1 +/- 9.3 on the subtracted images (P < 0.0001).
      CONCLUSION: Image subtraction significantly improved both the SNR and CNR, but
      did not alter the final diagnosis, and does not appear warranted in routine
      practice.

PMID- 11446752
TI  - Clinical and high-resolution computed tomographic findings in five patients with
      pulmonary tuberculosis who developed respiratory failure following chemotherapy.
AB  - AIM: The purpose of this study was to describe the clinical and high-resolution
      computed tomographic (HRCT) findings in patients with pulmonary tuberculosis who
      developed respiratory failure after starting chemotherapy. MATERIALS AND METHODS:
      The clinical records, chest radiographs, and HRCT findings in five patients with
      non-miliary pulmonary tuberculosis who developed respiratory failure after
      starting chemotherapy were reviewed. RESULTS: Chest radiographs taken early in
      the course of acute respiratory failure showed progression of the original
      lesions with (n = 4) or without (n = 1) new areas of opacity away from the site
      of the original lesions. HRCT demonstrated widespread ground-glass attenuation
      with a reticular pattern as well as segmental or lobar consolidation with
      cavitation and nodules, consistent with active tuberculous foci in all five
      cases. Prominent interlobular septal thickening was seen in two cases. Four of
      the five patients had received corticosteroids. Of these five, two died and three
      recovered with continued corticosteroid therapy. Transbronchial biopsy in three
      cases showed evidence of acute alveolar damage. CONCLUSION: In selected patients
      with tuberculosis who develop respiratory failure following the initiation of
      antituberculous therapy, HRCT may be a helpful adjunct to clinical evaluation in
      differentiating hypersensitivity reactions (presumed to be due to the release of
      mycobacterial antigens) from other pulmonary complications.

PMID- 11446753
TI  - Pre-operative sestamibi-technetium subtraction scintigraphy in primary
      hyperparathyroidism: experience with 156 consecutive patients.
AB  - AIM: The aim of this study was to assess the usefulness of pre-operative
      sestamibi-technetium subtraction scintigraphy in a large cohort of patients with
      primary hyperparathyroidism (HPT). MATERIALS AND METHODS: A group of 156
      consecutive patients with biochemically proven HPT underwent sestamibi-technetium
      subtraction scintigraphy before cervical exploration. Images were interpreted and
      reported prospectively and influenced the extent of surgical exploration. The
      intraoperative findings were compared retrospectively with the pre-operative
      scintigram reports in 154 individuals with technically satisfactory scintigrams.
      RESULTS: Of the 154 patients with satisfactory scintigrams, 122 (78.2%)
      demonstrated a single focus of activity following subtraction, 31 (19.9%) had
      negative findings and the remaining scintigram showed four foci of activity. At
      operation 138 (89.6%) solitary adenomas were removed, 13 patients (8.4%) had
      multi-gland disease and in three individuals (2.0%) no abnormal parathyroid
      tissue was found. The pre-operative scintigram accurately localized 91 of 98
      (92.9%) solitary tumours weighing > 500 mg but only 18 of 35 (51.4%) adenomas
      weighing < 500 mg, (P < 0.0001). Overall sensitivity of sestamibi-technetium
      scintigraphy for localizing single parathyroid adenomas was 83.7%. CONCLUSION:
      Sestamibi-technetium subtraction scintigraphy will accurately localize a high
      proportion of solitary parathyroid adenomas but its usefulness is diminished by
      its inability to consistently identify smaller tumours.

PMID- 11446754
TI  - Fluoroscopic-guided covered metallic stent placement for gastric outlet
      obstruction and post-operative gastroenterostomy anastomotic stricture.
AB  - AIM: To evaluate the feasibility and safety of fluoroscopic-guided covered
      metallic stent placements in providing palliative care for patients with
      inoperable malignant gastric outlet obstruction. MATERIALS AND METHODS: Under
      fluoroscopic guidance, placement of self-expandable, covered stents was attempted
      in 20 patients with inoperable or recurrent gastric cancer (age range 36-79
      years). All patients had inoperable gastric outlet obstruction, 13 with native
      anatomy and seven with post-operative anatomy (gastrointestinal anastomotic
      sites). All patients had intolerance to oral alimentation and/or vomiting after
      ingestion. Success was defined both technically and clinically. RESULTS: The
      placement of the stent was technically successful in 18 patients and failed in
      two patients (technical success: 90%). The cause of the technical failures was an
      inability to negotiate the guide wire through the obstruction sites in spite of
      the use of both fluoroscopic and endoscopic guidance. After stent placement, 15
      patients were able to ingest at least liquids and had a markedly decreased
      incidence of vomiting (clinical success: 75%). During the mean follow-up of 6
      weeks, there have been no stent reocclusion and no life-threatening complications
      except migration of two stents in one patient. CONCLUSION: Fluoroscopically
      guided covered metallic stent placement appears to be valuable for the palliative
      treatment of malignant obstruction of gastric outlet and post-operative
      gastrointestinal anastomoses.

PMID- 11446755
TI  - Primary antegrade ureteric stenting: prospective experience and cost
      effectiveness analysis in 50 ureters.
AB  - AIM: To evaluate the success rate and cost efficiency of primary antegrade
      ureteric stenting (antegrade ureteric stent insertion as a single procedure
      without preliminary drainage). MATERIALS AND METHODS: A policy of primary
      stenting was tested in 38 patients (50 ureters) with obstructive hydronephrosis,
      of acute or chronic onset and of benign or malignant origin. Patients with
      suspected pyonephrosis were excluded. Patients successfully primarily stented
      (group 1) were compared to a group stented as a traditional two-stage procedure
      (group 2). End point assessments were screening time, equipment used, procedure
      related costs, bed occupancy and technical and clinical success rate. Using these
      cost and outcome measures, a cost-efficiency analysis was performed comparing the
      two strategies. RESULTS: 40/50 (80%) ureters were considered primary stent
      successes. The average procedure-related bed occupancy was 2 days (range 1-2
      days). Simple equipment alone was successful in 16 cases. Van ( pound46/case).
      The mean screening time was similar for the two groups (13.5 min vs Andel
      dilatation catheters and peel-away sheaths were frequently used (23 ureters).
      Expensive equipment was rarely necessary (four cases) and average extra equipment
      cost was small 15.3 min; P > or = 0.05). There was a minimum saving of pound800
      per successful primary stent. The cost-effectiveness of a primary antegrade
      stenting strategy was pound1229 vs pound2093 for secondary stenting. CONCLUSION:
      In carefully selected patients, the majority of obstructed ureters can be
      primarily stented using simple equipment. The reduced hospital stay and overall
      success rate significantly improves the cost competitiveness of antegrade
      ureteric stenting.

PMID- 11446756
TI  - Prevalence of cystic paraurethral structures in asymptomatic women at endovaginal
      and perineal sonography.
AB  - AIM: To prospectively assess the prevalence of paraurethral cystic structures in
      asymptomatic adult women. PATIENTS AND METHODS: One hundred and forty consecutive
      women undergoing endovaginal sonography with no history of lower urinary tract
      symptoms. RESULTS: Paraurethral cystic structures were identified in 4/140
      subjects (2.9%). Ultrasound assessment allowed rapid definition of the site, size
      and vascularity of these lesions and was well tolerated by the patient.
      CONCLUSION: This is the first prospective ultrasound study to determine the
      prevalence of paraurethral cystic structures in a large consecutive cohort of
      asymptomatic women. Our findings are in accordance with previously published post
      mortem data and surgical series which have estimated the prevalence of
      paraurethral cystic structures to be between 1 and 6%.

PMID- 11446757
TI  - Hepatic artery pseudoaneurysms following liver transplantation: incidence,
      presenting features and management.
AB  - AIM: Hepatic artery pseudoaneurysm (PA) is an uncommon complication of liver
      transplantation. We report a series of 13 patients, the largest published review
      including outcome. The presenting features, risk factors and role of radiology in
      the diagnosis and management of this frequently fatal complication are discussed.

PMID- 11446758
TI  - Magnetic resonance study of multiple primitive neuroectodermal tumours of the
      cerebrum, cerebellum and spinal cord in an adult.

PMID- 11446759
TI  - Biliary papillomatosis complicating recurrent pyogenic cholangitis.

PMID- 11446760
TI  - Meckel's diverticulitis due to an obstructing enterolith: ultrasound and CT
      appearances.

PMID- 11446761
TI  - Tc-99m sulphur colloid scintigraphy in the assessment of residual splenic tissue
      after splenectomy.

PMID- 11446762
TI  - Cystic mesenchymal hamartoma mimicking hepatic hydatid disease.

PMID- 11446763
TI  - Superficial haemosiderosis secondary to cutaneous venous malformation.

PMID- 11446764
TI  - Giant myelipoma of the adrenal gland.

PMID- 11446765
TI  - Implication of stem cell factor in the proliferation of choroidal melanocytes.
AB  - The tyrosine kinase receptor c-kit and its ligand stem cell factor exert a broad
      range of biological activities during organogenesis. It also improves normal cell
      development including complex biological responses involved in the
      differentiation and proliferation of the melanocytes. Diffuse uveal melanocytic
      proliferation is a rare paraneoplasic syndrome, resulting in rapid bilateral
      visual loss due to proliferation of melanocytes within the choroid. We have
      therefore investigated whether the c-kit/stem cell factor pathway regulates the
      proliferation of choroidal melanocytes and also if such pathway plays a role in
      bilateral uveal melanocytic proliferation. Normal cultured melanocytes of the
      choroid and paraffin-embedded sections of melanocytic proliferation were studied.
      C-kit expression and effects of stem cell factor were measured. Western blot
      assays of cell extracts demonstrated that c-kit was expressed in choroidal
      melanocytes. Immunocytochemical analysis on cultured melanocytes showed a
      cytoplasmic distribution. Immunohistochemical analysis on melanocytic
      proliferation showed a strong cytoplasmic distribution in the pigmented spindle
      shaped melanocytes localized in the multiple focal areas of choroidal thickening.
      The addition of stem cell factor did not change melanocyte morphologies and was
      mitogenic in the presence of bFGF, isobutyl-1-methylxanthine and cholera toxin.
      In contrast, stem cell factor was not able to produce any significant melanin.
      Activation of c-kit by its ligand may contribute to the proliferation of
      choroidal melanocytes.

PMID- 11446766
TI  - Vitamin C transport in human lens epithelial cells: evidence for the presence of
      SVCT2.
AB  - Vitamin C [ascorbic acid (AA)] is an important antioxidant present in m M amounts
      in the aqueous humor. Recently, two specific transporters for vitamin C (SVCT1,
      SVCT2) have been cloned in the rat and the human. The aim of the present study
      was to characterize vitamin C transport in an immortalized human lens epithelial
      cell line (HLE-B3). AA uptake was linear for 120 min in experiments conducted
      with 14C AA + 40 microM unlabelled AA. Uptake was measured at varying AA
      concentrations (0.04-1 m M) in Na+-containing and Na+-free buffers for 30 min at
      37 degrees C. Effect of potential inhibitors of AA transport was also examined.
      Presence (or absence) of SVCT1 and SVCT2 was studied by RT-PCR of HLE-B3 poly
      (A)+ RNA using gene specific primers. Uptake studies revealed that AA uptake was
      highly Na+-dependent and exhibited saturation. Na+-dependent 14C-AA uptake was
      strongly inhibited (85-90%) by 10 m M unlabelled AA. Incubation of HLE-B3 cells
      with cAMP (0.1 m M), cytocholasin B (0.1 m M) and phorbol dibutyrate (1 microM)
      resulted in partial inhibition (36-51%) of AA uptake. Under similar conditions, D
      -glucose (10 m M) and staurosporine (0.1 microM) had no effect. RT-PCR showed the
      presence of SVCT2 while SVCT1 could not be amplified. Exposure to the chemical
      oxidant tert-butylhydroperoxide (TBH) up-regulated SVCT2 gene expression in HLE
      B3 cells. Our data suggest that Na+-dependent transport of AA in normal lens
      epithelium is most likely mediated by SVCT2 rather than by SVCT1. This transport
      system may be subject to regulation by oxidant stress and by various second
      messenger signals.

PMID- 11446767
TI  - Kappa opioid agonist-induced changes in IOP: correlation with 3H-NE release and
      cAMP accumulation.
AB  - Opioid receptors have been demonstrated to modulate various functions in the eye.
      This research project was designed to determine and compare the effects of kappa
      opioid agonists on selected parameters that influence ocular hydrodynamics.
      Experiments determined the effects of two relatively selective kappa opioid
      receptor agonists, ICI 204 448 (ICI), which has limited ability to penetrate the
      blood-brain barrier, and spiradoline mesylate on: (1) in vivo parameters,
      intraocular pressure (IOP) and pupil diameter (PD); and (2) in vitro parameters,
      neurotransmitter release and cAMP accumulation, in the ciliary body. Dark
      adapted, reverse light cycle New Zealand white (NZW) male rabbits were used in
      all experiments. In in vivo experiments, intraocular pressures and pupil
      diameters were measured by a pneumatonometer and an optistick, respectively,
      before and after drug administration. Baseline readings were taken at 0.5 and 0
      hr prior to agonist administration. Postdrug IOP and PD measurements were made at
      0.5, 1, 2, 3, 4 and 5 hr after agonist application. In some experiments, the
      relatively selective kappa antagonist, norbinaltorphimine was applied 30 min
      prior to agonist application. In in vitro experiments, the release of tritiated
      norepinephrine (3H-NE) was measured from perfused electrically stimulated iris
      ciliary bodies and expressed as the percent change of the control. Basal and
      isoproterenol-stimulated cyclic AMP concentrations in iris ciliary bodies were
      quantified by radioimmunoassay techniques in the presence and absence of ICI and
      spiradoline. ICI and spiradoline decreased IOP in a dose-dependent manner in
      normal rabbits, but only spiradoline produced significant changes in PD. The
      kappa opioid receptor antagonist, norbinaltorphimine, antagonized the hypotensive
      effects of spiradoline and ICI in IOP experiments. Both kappa agonists inhibited
      the release of norepinephrine from perfused iris ciliary bodies. Isoproterenol-
      stimulated cAMP levels in iris ciliary bodies were suppressed by both kappa
      receptor agonists. The antagonism by norbinaltorphimine suggests that ICI and
      spiradoline lower IOP by activating kappa opioid receptors in the eye. The
      bilateral effects of unilaterally applied spiradoline on PD indicate that this
      kappa agonist activates receptors in the iris and/or the brain. The inhibition of
      norepinephrine release and cAMP accumulation in the iris ciliary body by ICI and
      spiradoline suggests that there are both pre- and postjunctional sites of action
      for kappa agonists.

PMID- 11446768
TI  - Altered expression of growth factors and cytokines in keratoconus, bullous
      keratopathy and diabetic human corneas.
AB  - The purpose of this study was to identify the growth factors and cytokines
      present in normal and diseased corneas. Total RNA was isolated from normal and
      diseased corneas. cDNA was synthesized from individual corneas and
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was
      performed with primers to IL-1alpha, 1IL-8, PDGF-B, BMP-2, BMP-4, IGF-I, TGF
      beta2, FGF-2, and VEGF. After normalization to beta2-microglobulin, several
      factors were identified that were significantly different from normal. Antibodies
      to IGF-I, BMP-2, VEGF and TGF-beta2 were used for immunohistochemistry. A total
      of 93 corneas were used for this study including 31 normal, 20 keratoconus, 19
      bullous keratopathy (pseudophakic and aphakic, PBK/ABK), and 23 diabetic corneas.
      The VEGF RNA levels were significantly decreased in the keratoconus and PBK/ABK
      corneas but increased in the diabetic corneas. BMP-2 gene expression was lower
      than normal in the PBK/ABK and diabetic corneas. IGF-I and BMP-4 RNA levels were
      increased in PBK/ABK. In the immunohistochemical studies, the protein patterns
      paralleled those found at the mRNA level. The only exception was IGF-I in
      diabetic corneas that showed increased staining in the epithelium and its
      basement membrane without a significant increase in mRNA levels. TGF-beta2 mRNA
      and protein levels were similar to normal in all diseased corneas. Thus, no
      alterations in the tested growth factors/cytokines were unique to keratoconus
      corneas. In contrast, PBK/ABK corneas had specific significant elevations of BMP
      4 and IGF-I. Diabetic corneas were unique in their increased VEGF mRNA levels.
      These data suggest that while some growth factor/cytokine alterations are non
      specific and can be found in multiple corneal diseases, there are others that are
      unique to that disease.

PMID- 11446769
TI  - HGF- and KGF-induced activation of PI-3K/p70 s6 kinase pathway in corneal
      epithelial cells: its relevance in wound healing.
AB  - In this study we have investigated the involvement of PI-3K and its downstream
      target p70 S6K in the signaling response of corneal epithelial cells after HGF
      and KGF stimulation. HGF induced three- to five-fold increase in PI-3K activity
      in 5-10 min, whereas KGF stimulation resulted in two- to three-fold increase in
      activity in 2-10 min. Both growth factors also caused the phosphorylation of p70
      S6K and stimulation of its activity. HGF increased p70 S6K activity by 300% and
      KGF by about 200%. Protein kinase C (PKC) activator TPA also induced the
      phosphorylation of p70 S6K. Both the PI-3K inhibitor wortmannin and PKC inhibitor
      calphostin C blocked the phosphorylation of p70 S6K mediated by the growth
      factors. However, the mitogen-activated protein kinase (p42/44 MAPK) cascade
      inhibitor PD98059 had no effect on p70 S6K activation. Furthermore, HGF and KGF
      increased the rate of corneal epithelial wound healing in an organ culture model,
      and wortmannin and rapamycin (the p70 S6K inhibitor) blocked corneal epithelial
      wound healing promoted by the growth factors. These studies suggest that PI-3K
      and p70 S6K are important signal transducers in the stimulation of corneal
      epithelial cells by HGF and KGF. PKC is involved in the PI-3K-dependent
      activation of p70 S6K but not MAPK. Inhibition of wound closure by PI-3K and p70
      S6K inhibitors suggests these enzymes play a significant role in corneal wound
      repair stimulated by HGF and KGF.

PMID- 11446770
TI  - Resistance of human betaB2-crystallin to in vivo modification.
AB  - Post-translational modifications and/or structural changes induced by
      modifications are likely causes of the decrease in crystallin solubility
      associated with aging and the development of cataract. Characterization of human
      lens crystallins by mass spectrometry has demonstrated that betaB2-crystallin
      undergoes less modification than any of the other crystallins. As the lens ages,
      betaB2-crystallin retains its hydrophilic N-terminus while the hydrophilic C
      termini of alpha-crystallins and large portions of the N-termini of betaA3/A1 and
      betaB1 are truncated. The hydrophilic terminal regions of crystallins contribute
      to their solubility. Furthermore, deamidation and disulfide bond formation, other
      modifications that may affect solubility by altering conformation, are less
      extensive in betaB2 than in the other crystallins. This resistance to
      modification results in higher levels of betaB2 compared with the other
      crystallins in the water-soluble fraction of older lenses. The solubility of
      betaB2 and its propensity to form non-covalent associations with less soluble
      beta-crystallins may contribute to the solubility of the other beta-crystallins.
      A current hypothesis is that the chaperone-like properties of alpha-crystallins
      contribute to lens crystallin solubility, particularly in younger lenses. In
      older lenses, where most of the alpha-crystallins have become water-insoluble,
      betaB2-crystallins may play a dominant role in lens crystallin solubility.

PMID- 11446771
TI  - Characterization of membrane steroid binding protein mRNA and protein in lens
      epithelial cells.
AB  - Epithelial cells of the ocular lens contain a 28 kDa membrane protein which is
      proposed to mediate high affinity binding of steroid hormones and rapid non
      genomic actions of steroid hormones. It has been named membrane steroid binding
      protein (MSBP). Our purpose was to further characterize this protein from
      cultured bovine lens epithelial cells (BLEC) and compare it to similar forms of
      the protein present in other species and tissues. The size of the protein's mRNA
      was examined by Northern blot analysis using a digoxigenin-labelled antisense
      riboprobe. The sequence of the mRNA was obtained by RT-PCR amplification of poly
      A+ RNA recovered from cultured BLEC. PCR amplification was conducted using three
      sets of nested sense and antisense primers, one set at a time. The amino acid
      sequence of the lens protein was deduced from the revealed cDNA sequence. The
      hydropathy of the protein was examined by Kyte-Doolittle plots. The sequence of
      the lens protein's cDNA (about 1.7 kb total) described an open reading frame of
      582 residues which coded for a protein of 194 amino acids. The presence of a C
      terminal isoprenylation motif suggested by earlier work was not found in the
      coding region. The deduced amino acid sequence of the lens protein was extremely
      similar to those of other species and tissues, being 95-98% homologous with that
      of the other members. All of the MSBPs apparently contain a single membrane
      spanning domain in the amino terminal. The highly conserved nature of this
      protein implies a useful function to the cell. We speculate that the protein is a
      receptor which mediates rapid actions of steroids on lens epithelial cells, such
      as calcium mobilization, and that the protein plays a role in the mechanism of
      steroid induced cataracts.

PMID- 11446772
TI  - Age-related telomere shortening occurs in lens epithelium from old rats and is
      slowed by caloric restriction.
AB  - We have investigated whether the average relative telomere length of lens
      epithelial cells (LECs) from brown Norway rats decreases with the age of the
      donor animal, and whether chronic caloric restriction (CR) of the rats delays the
      telomere shortening. Our previous studies have demonstrated that clonal
      proliferative potential of rodent LECs as well as the in vivo rate of DNA
      synthesis decreases with age and that this decrease is slowed by chronic lifelong
      caloric restriction (CR). In order to determine if telomeric shortening might be
      involved in this loss of proliferative potential, we examined relative telomeric
      lengths in young, old ad lib fed (AL), and old calorically restricted (CR) brown
      Norway rats. We used fluorescence in situ hybridization with a peptide nucleic
      acid probe (PNA) complementary to the telomeric repeat sequence to quantitate
      relative telomere lengths in LECs in lens sections (TELO-FISH). Control
      experiments demonstrated that the PNA probe binding was restricted almost
      entirely to the terminal portions of the rat chromosomes with less than 5% bound
      at interstitial sites in typical metaphase spreads. The relative telomere lengths
      of interphase human fibroblast standards, as determined by TELO-FISH, were in
      good agreement with terminal restriction fragment analyses of the same standards
      and with literature values for rat cells. The average telomere lengths of
      interphase nuclei in the old AL rat LECs were found to be 21% shorter than paired
      young AL controls (P < 0.01 by Wilcoxian signed rank test). The calorically
      restricted old rats had less telomere erosion (12%) than the old AL group (P <
      0.05). Although it is not clear whether such moderate telomeric erosion can limit
      cell division in rodent LECs, the telomeric shortening correlated well with
      previous studies demonstrating reduced clonal, replicative potential, and reduced
      rates of in vivo DNA replication in LECs from old rodents and a delay in this
      attenuation in animals on chronic CR.

PMID- 11446773
TI  - Removal of oxidatively damaged proteins from lens cells by the ubiquitin
      proteasome pathway.
AB  - Understanding how oxidized proteins are removed is important since accumulation
      of such damaged proteins is causally related to cellular and organismic
      dysfunction, disease and aging. Previous work showed that activity of the
      ubiquitin-proteasome pathway (UPP) in lens cells increased during recovery from
      oxidative stress ( Shang et al., 1997b : J. Biol. Chem. 272, 23086-93). In this
      study we sought to determine if the up-regulation of the UPP during recovery from
      oxidative stress has a role in selective removal of oxidized proteins from the
      cells. In cells which were not exposed to peroxide, inhibition of the proteasome
      with MG132 or clasto-lactacystin beta-lactone had little effect on protein
      carbonyl levels. However, inhibition of the proteasome in the 20 microM peroxide
      treated cells caused an approximate 60% increase in levels of protein carbonyl
      and an approximate 100% increase in levels of ubiquitin conjugates. The carbonyl
      containing proteins that accumulated in the presence of the proteasome inhibitor
      co-localized with high molecular mass ubiquitin-protein conjugates. Furthermore,
      isolated carbonyl-containing proteins from H2O2-treated cells were ubiquitinated,
      and ubiquitin-conjugates were enriched with carbonyl-containing proteins. The
      diminished effect of proteasome inhibitors on protein carbonyl levels, together
      with the robust increase in ubiquitin-protein conjugates and accompanied
      increases in oxidized proteins, upon exposure to 60 microM H2O2 indicate that the
      proteasomal step of the UPP is more susceptible to oxidative inactivation than
      the ubiquitination step. In fact, oxidative stress is associated with a
      hyperactivation of the ubiquitin-activating enzyme. These data indicate that the
      UPP plays a role in removal of oxidatively damaged proteins from cells and that
      attenuation of the UPP activity may result in cytotoxic accumulation of damaged
      proteins, possibly including the ubiquitinated forms.

PMID- 11446774
TI  - Effect of perillic acid, a putative isoprenylation inhibitor, on the cultured rat
      lens.
AB  - Previous studies have demonstrated that agents affecting the cholesterol
      synthetic pathway can have cataractogenic effects. We have suggested that
      opacification of cultured lenses resulting from exposure to the cholesterol
      lowering agent lovastatin is caused by inhibition of isoprenylation of small
      GTPases. To test that hypothesis we have investigated the effects of perillic
      acid, an agent reported to inhibit isoprenylation, on rat lenses in organ
      culture. Perillic acid caused dose and time dependent opacification of cultured
      lenses. While the opacities appeared grossly similar to those produced by
      lovastatin, they differed dramatically when analysed histologically. It also
      produced marked morphological changes to lens epithelial cells in culture.
      Analysis of small GTPases in the perillic acid treated cells failed to detect any
      accumulation in the water soluble fraction as would be expected if isoprenylation
      was inhibited. Further, studies on the isoprenylation of radiolabelled
      isoprenoids into proteins in cultured lenses showed no significant decrease
      following perillic acid exposure. It was concluded that perillic acid causes
      cataract in this system by a mechanism different from lovastatin and that
      inhibition of isoprenylation is unlikely to be a primary factor in the perillic
      acid cataract.

PMID- 11446775
TI  - Bcl-2 expression in the human cornea.
AB  - The purpose of this study was to determine the localization of Bcl-2 protein in
      the human cornea. Anti-human Bcl-2 monoclonal antibodies (MAbs) against selective
      Bcl-2 peptide sequences were used to localize Bcl-2 protein immunocytochemically
      in fresh eye bank donor human corneas (n = 4). Specificity of each MAb was
      determined by Western blot analysis of pooled protein extracted from human
      corneal epithelium (n = 3). Expression of Bcl-2 protein in apoptotic surface
      epithelial cells was detected by co-labeling with TUNEL assay and anti-Bcl-2
      antibody staining. Two MAbs specific for amino acids residues (aa) 41-54 within
      the loop domain of Bcl-2 protein stained nuclei of all corneal epithelial cell
      layers. MAb specific for aa 61-76, also within the loop domain, produced faint
      nuclei and nuclear envelope staining. Occasional corneal surface epithelial cells
      however, consistently lacked anti-Bcl-2 nuclear staining with these three MAbs;
      concomitant TUNEL assay revealed that all TUNEL positive-surface cells were Bcl-2
      negative. In the stroma, keratocytes showed similar but weak anti-Bcl-2 staining.
      All corneal endothelial cells showed intense nuclear staining with MAbs, with no
      gradient or absence of staining. In summary, Bcl-2 protein can be localized to
      the nuclei and nuclear envelope of corneal epithelial cells, keratocytes and
      endothelial cells with the use of MAbs specific for the loop domain of Bcl-2.
      TUNEL-labeled surface epithelial cells did not stain with MAbs to Bcl-2,
      suggesting degradation or epitope masking perhaps by specific phosphorylation of
      the loop domain during apoptosis. Taken together, these findings suggest that Bcl
      2 protein may play a critical role in modulating apoptotic cell desquamation in
      the human corneal epithelium.

PMID- 11446776
TI  - The functional unit of interphotoreceptor retinoid-binding protein (IRBP)-
      purification, characterization and preliminary crystallographic analysis.
AB  - To define the relationship between the structure and function of
      interphotoreceptor retinoid-binding protein (IRBP) we seek to prepare crystals of
      IRBP suitable for X-ray crystallographic analysis. As recent studies suggest that
      each of IRBPs four homologous regions or modules possess ligand-binding activity,
      we here explore the feasibility of preparing crystals from an individual module.
      Xenopus laevis IRBP, which has a similar four-module structure as that of
      mammalian and avian IRBPs, was selected for these studies in view of the
      advantage of the Xenopus retina for cellular and transgenic approaches. In the
      present study we focused on the second module of Xenopus IRBP. This module was
      expressed as a thioredoxin/histidine-patch fusion protein to promote its soluble
      expression in Escherichia coli and subsequent purification. The ligand-binding
      properties of the fusion protein were determined by fluorescence spectroscopy.
      For the preparation of crystals, the module was enzymatically separated from the
      fusion tag. Crystals of the native and selenomethionine derivatized module were
      prepared by vapor diffusion in hanging drops. Module II of IRBP binds 1.57 +/-
      0.041 and 1.49 +/- 0.15 equivalents of at all- trans retinol and 9-(9
      anthroyloxy) stearic acid, respectively, with KDs in the 0.1 microM range.
      Crystals of this module had an elongated rectangular beam-like morphology. A
      complete dataset of a frozen selenomethionine crystal extending to 1.85 A
      resolution was collected. Focusing on the individual modules will likely provide
      an effective strategy to correlate biochemical and structural data to define the
      functional domains of IRBP. The quality and resolution of the data obtained
      suggests that it will be possible in the near future to solve the X-ray crystal
      structure of the IRBP modules.

PMID- 11446777
TI  - Regulation of cAMP by light and dopamine receptors is dysfunctional in
      photoreceptors of dystrophic retinal degeneration slow(rds) mice.
AB  - cAMP levels in dark and light were studied in dystrophic retinal degeneration
      slow(rds) mice, which carry a mutation in the rds/peripherin gene. cAMP levels
      were measured in vivo, in freshly isolated retinas, and in vitro in the presence
      of glutamate, which confines light modulation to photoreceptors. Experiments were
      conducted on young animals, when significant numbers of viable photoreceptor
      cells are present. In vivo levels of cAMP are higher in illuminated rds/rds
      retinas than levels measured in normal BALB/c retinas. Light-evoked down
      regulation of cAMP levels was observed in vitro in normal photoreceptors. These
      measurements were made in the presence of the cyclic nucleotide phosphodiesterase
      inhibitor, 3-isobutyl-1-methylxanthine; therefore, they reflect an inhibition of
      cAMP formation. In contrast, light had no effect on cAMP formation in
      photoreceptors of mutant mice, measured under identical conditions. Thus,
      elevated levels of cAMP in rds/rds retinas in vivo result from abnormalities in
      cAMP synthesis in the mutant photoreceptor cells. In addition to regulation by
      light, cAMP formation in photoreceptor cells is regulated by dopamine, acting
      through dopamine D4 receptors. A dopamine D2/D4 receptor agonist, quinpirole,
      reduced cAMP levels in dark-adapted normal retinas in vitro, but not in rds/rds
      retinas. Our data indicate that alterations in a signal transduction pathway that
      leads to inhibition of adenylyl cyclase might underlie the abnormalities in cAMP
      levels in mutant rds/rds retinas. Heterozygous rds/+ photoreceptors demonstrated
      a normal pattern of light-evoked and quinpirole-mediated down-regulation of cAMP.
      Thus, partial expression of the normal phenotype is sufficient to render normal
      characteristics of cAMP regulation to the photoreceptors of the heterozygous
      mouse. The data obtained in the present study might be relevant to the
      understanding of photoreceptor pathology of patients with peripherin/rds
      mutations.

PMID- 11446778
TI  - Retinoic acid-dependent transgene expression is regulated by RARbeta expression
      in the retina.

PMID- 11446779
TI  - Microcystin-LR Adsorption by Activated Carbon.
AB  - We use a selection of wood-based and coconut-based activated carbons to
      investigate the factors controlling the removal of the hepatotoxin microcystin-LR
      (m-LR) from aqueous solutions. The wood carbons contain both micropores and
      mesopores. The coconut carbons contain micropores only. Confirming previously
      published observations, we also find that the wood-based carbons adsorb more
      microcystin than the coconut-based carbons. From a combination of a judicious
      modification of a wood-based carbon's surface chemistry and of the solution
      chemistry, we demonstrate that both surface and solution chemistry play minor
      roles in the adsorption process, with the adsorbent surface chemistry exhibiting
      less influence than the solution chemistry. Conformational changes at low
      solution pH probably contribute to the observed increase in adsorption by both
      classes of adsorbent. At the solution pH of 2.5, the coconut-based carbons
      exhibit a 400% increased affinity for m-LR compared with 100% increases for the
      wood-based carbons. In an analysis of the thermodynamics of adsorption, using
      multiple temperature adsorption chromatography methods, we indicate that m-LR
      adsorption is an entropy-driven process for each of the carbons, except the most
      hydrophilic and mesoporous carbon, B1. In this case, exothermic enthalpy
      contributions to adsorption also exist. From our overall observations, since m-LR
      contains molecular dimensions in the secondary micropore width range, we
      demonstrate that it is important to consider both the secondary micropore and the
      mesopore volumes for the adsorption of m-LR from aqueous solutions. Copyright
      2001 Academic Press. 

PMID- 11446780
TI  - Effect of Gravity on Colloidal Deposition Studied by Atomic Force Microscopy.
AB  - Atomic force microscopy (AFM) was used to study the effect of gravitational
      forces on the deposition of submicrometer colloidal particles onto solid surfaces
      to test the usual assumption that the contribution of gravity to the behavior of
      particles with diameters <1 &mgr;m is negligible. The effects of both particle
      size and density were examined using polystyrene sulfate latex, silica, and
      colloidal gold particles of several sizes ranging from 10 nm to 1 &mgr;m. The
      results show that significant differences are observed in the deposition of
      colloidal particles onto horizontal and vertical surfaces, under identical
      suspension conditions and exposure times, showing that gravitational forces can
      have a considerable effect. This effect was quantified by analysis of the AFM
      images. The experimental results are compared to calculations of the expected
      coverage and particle surface concentration assuming diffusion-limited adsorption
      and deposition by sedimentation. Gravity can be negligible for low-density
      particles with diameters considerably smaller than 1 &mgr;m. However, if the
      density of the colloidal particles is high, as in the case of colloidal gold,
      gravity can become a significant driving force for particle transport to the
      surface, even for particles with diameters much smaller than 100 nm. Copyright
      2001 Academic Press. 

PMID- 11446781
TI  - Development of Automatic Adsorption Apparatus for Binary Mixture: Measurement of
      Individual Adsorption Isotherms of Ethanol and Water from Their Mixed Vapors by
      Active Carbon Fiber.
AB  - The automatic adsorption apparatus has been developed to measure the individual
      adsorption isotherms of constituent vapor from binary mixed vapor. The present
      adsorption apparatus consists of a combination of gravimetry and volumetry. The
      weight increase due to gas adsorption was determined by the magnetic suspension
      vacuum balance with a sensitivity of 0.01 mg, while the pressure decrease due to
      adsorption was measured by a high precision pressure gauge with a sensitivity of
      0.2 Pa. The adsorption data obtained from both gravimetry and volumetry make it
      possible to determine the individual isotherms of the constituent vapors without
      chemical analysis, if the molecular weights of the constituent vapors are
      significantly different one another. In the later part of this work, the present
      adsorption apparatus has been applied to measure the individual adsorption
      isotherms of ethanol and water by active carbon fiber from their mixed vapor. The
      reliability of the individual isotherms measured by the present apparatus has
      been considered. The adsorption data obtained in the present work clearly
      indicate that ethanol molecules are preferentially adsorbed into the micropores
      of active carbon fiber with a pore width of 0.67 nm. The present adsorption
      result suggests the possibility of the energy-saving separation of ethanol from
      the mixed vapors of ethanol and water. Copyright 2001 Academic Press. 

PMID- 11446782
TI  - Effect of a Decapeptide (VPDLLADLLK) on the Phase Transition of
      Dimyristoylphosphatidylcholine Lipid Bilayer.
AB  - VPDLLADLLK is a synthetic decapeptide, which shows a difference in conformation
      in various environments. Circular dichroism spectral studies show that it exists
      in an unordered conformation in the aqueous phase, and in
      dimyristoylphosphatidylcholine (DMPC) lipid bilayer, it exhibits an alpha-helical
      structure. The membrane property modification due to the peptide incorporation
      has been studied by using differential scanning calorimetry and fluorescence
      spectroscopy. With incorporation of the peptide the average steady-state
      anisotropy of DPH in the membrane decreases slightly in the gel state but remains
      more or less the same in the liquid crystalline state. The peptide incorporation
      causes a shift in the phase-transition temperature from 23 to 26 degrees C for 15
      mol% and 29 degrees C for 30 mol% of the peptide, which is accompanied by a
      decrease in the sharpness and a broadening of the DSC thermogram. This
      preferential stabilization of the more ordered gel phase by the peptide could be
      due to the hydrophobic mismatch between the length of the peptide and the length
      of the hydrophobic segment of the DMPC bilayer. Copyright 2001 Academic Press. 

PMID- 11446783
TI  - Stabilization of Solutions of Feather Keratins by Sodium Dodecyl Sulfate.
AB  - Feather keratins were extracted from chicken feathers with aqueous solutions of
      urea and 2-mercaptoethanol. After filtration of the insoluble residue, a feather
      keratin solution was obtained. Removal of 2-mercaptoethanol and urea by dialysis
      resulted in aggregation of the keratin polypeptide chains and oxidation of the
      cysteine residues to afford a gel. The addition of sodium dodecyl sulfate (SDS)
      to the keratin solution prior to dialysis prevented extensive aggregation of the
      keratin chains. The effect of the addition of various quantities of SDS on the
      rate of aggregation of the polypeptide chains and the rate of oxidation of
      cysteine residues during dialysis was studied. With size exclusion
      chromatography, it was found that lower initial SDS/keratin ratios (0.125-0.5 g
      SDS/g keratin) resulted in larger SDS-keratin complexes. This indicates that more
      intermolecular cross-links had formed. Higher SDS/keratin ratios (1-2 g SDS/g
      keratin) resulted in small SDS-keratin complexes, comparable in size to the
      keratin monomer. High amounts of SDS seemed to prevent the oxidation reaction
      between different keratin chains, resulting in more intramolecular disulfide bond
      formation. Copyright 2001 Academic Press. 

PMID- 11446784
TI  - Synthesis and Characterization of Spherical Magnetite/Biodegradable Polymer
      Composite Particles.
AB  - A method for preparing colloidal particles formed by a magnetite nucleus and a
      biodegradable poly(DL-lactide) polymer coating is first described. The method is
      based on the so-called double-emulsion technique, employed to obtain polymeric
      spheres loaded with therapeutic drugs, to be used as drug delivery vectors. The
      aim of this work was to obtain, in a reproducible and rather simple way,
      colloidal particles that were both magnetic field responsive, and useful as drug
      delivery systems. In order to investigate to what extent is this target achieved,
      we compare the structure, chemical composition, and surface properties of the
      composite particles with those of the nucleus and the coating material. Although
      the surface properties of the magnetite core are not completely masked, this
      preliminary study shows that the synthetic new material displays a behavior
      intermediate between that of magnetite and poly(DL-lactide) spheres. Thus,
      electrophoresis measurements as a function of pH shows that the isoelectric point
      (pH(iep)=5.2) of core/shell colloids is in between those of magnetite (pH(iep)=7)
      and polymer (pH(iep)<2). A similar conclusion is reached when a surface
      thermodynamic study is performed on the three types of particles: the electron
      donor component of the surface free energy of the solids is the quantity that
      appears to be most sensitive to the surface composition. The fact that poly(DL
      lactide) is close to being a nonpolar material gives rise to a measurable
      decrease in the electron-donor component of the surface free energy, although the
      effect of coating is also observable in the electron-acceptor and the apolar van
      der Waals component. Copyright 2001 Academic Press. 

PMID- 11446785
TI  - Magnetic Properties of Composite Hematite/Yttrium Oxide Colloidal Particles.
AB  - The effect of the shell thickness and density on the magnetic properties of
      composite colloidal particles consisting of a hematite (alpha-Fe(2)O(3)) core and
      an yttrium oxide (Y(2)O(3)) layer is described. Pure iron oxide colloidal spheres
      show two clearly different trends of variation of their magnetic susceptibility,
      chi(m), with temperature. Below T(M) approximately 220 K, chi(m) shows a slight
      increase when the particles are heated; a sharp transition is observed at such a
      critical temperature, whereby chi(m) increases almost 3 times in a very narrow
      temperature interval, decreasing slowly afterward. This is the result of a well
      known transition from perfect to imperfect antiferromagnetism (canted
      antiferromagnetism). Three types of core/shell particles have been prepared, and
      a gradual change is observed in chi(m) from that of hematite to that of pure
      Y(2)O(3). Even the most efficiently covered particles still show a change in
      their chi(m)-T trends around T(M), and are clearly distinct from Y(2)O(3)
      particles. Magnetization curves show that coating of hematite particles induces
      significant changes in the coercivity of the samples. The latter is always larger
      for composite than for core particles. Copyright 2001 Academic Press. 

PMID- 11446786
TI  - Electrical Double-Layer Effects on the Brownian Diffusivity and Aggregation Rate
      of Laponite Clay Particles.
AB  - Dynamic light scattering was used to study the Brownian translational diffusion
      and rate of Brownian aggregation of Laponite (RD) clay particles at low
      (millimolar) electrolyte concentrations. Laponite is a manufactured clay
      consisting of monodisperse disk-shaped particles with a 30-nm diameter and a 1-nm
      thickness. The stability ratio, defined as the ratio of the coagulation rate for
      Brownian spheres with no particle interactions to the observed coagulation rate,
      was quite large O(10(5)), suggesting that there was a large potential energy
      barrier to Brownian aggregation. The apparent potential energy barrier for face
      edge aggregation was rationalized on the basis of a calculation of the
      electrostatic interactions between two disks with negative face charges and
      positive rim charges. The aggregation rate increased with increasing electrolyte
      concentration owing to the screening of the electrostatic repulsion associated
      with the net charge on the particle. The rate decreased with increasing pH
      because of the decreasing positive charge on the rim. The translational
      diffusivity of the individual particles before the onset of aggregation exhibited
      a strong dependence on the electrolyte concentration and was as much as 50%
      smaller than the diffusivity for an uncharged disk. This effect is attributed to
      the added drag resulting from the electroviscous effects in the deformed double
      layer. The electroviscous effect on the diffusion of the disk-like particles is
      much stronger than that on rods and spheres. Copyright 2001 Academic Press. 

PMID- 11446787
TI  - Collision Kinetics and Electrostatic Dispersion of Airborne Submicrometer Fractal
      Agglomerates.
AB  - Collision and electrostatic dispersion rates of airborne submicrometer TiO(2)
      agglomerates were measured and compared with the classical collision theory for
      spheres as well as with models accounting for the agglomerate structure in terms
      of the fractal dimension and electrostatic effects such as Coulomb and van der
      Waals interactions. According to the authors' knowledge, this is the first time
      that the agglomerate fractal dimension and electrostatic effects have been
      considered simultaneously in determining the collision frequency function of
      agglomerates. The observed enhancement in the collision frequency of agglomerates
      was found mainly to be a result of electrostatic particle interactions.
      Nonspherical particle shape has only a comparatively small influence on the
      collision probability, on the order of 10-20%. Electrostatic dispersion
      coefficients of agglomerates were found to be similar to those of spheres.
      Copyright 2001 Academic Press. 

PMID- 11446788
TI  - Multiple Light Scattering by Spherical Particle Systems and Its Dependence on
      Concentration: A T-Matrix Study.
AB  - The T-matrix method has been used to calculate scattering cross-sections of two
      spherical particles close to each other. By comparing our results with those
      expected for infinite distance, we can determine the maximum distance required to
      produce interparticle light-scattering interactions. As a result, we can
      determine the degree of dilution needed in a particle suspension to remain within
      the single-scattering approximation. Cross sections have been calculated for a
      relative refractive index m=1.2 and a range of particle sizes and separations.
      Since the approach in this paper assumes double scattering as the first mechanism
      for beginning multiple scattering, our results will be compared with those
      arising from the condition that the optical depth is less than unity, tau<1. It
      is shown that this condition, widely used in transfer theory, is more restrictive
      than ours except for the smallest particles, where double scattering becomes the
      main agent for multiple scattering. Copyright 2001 Academic Press. 

PMID- 11446789
TI  - Preparation of Silica Particles Encapsulating Retinol Using O/W/O Multiple
      Emulsions.
AB  - Retinol, a cosmetic ingredient, was entrapped within inorganic microspheres
      obtained from sol-gel reaction of TEOS in o/w/o multiple emulsions as
      microreactors. In o/w/o multiple emulsions, the retinol was emulsified as an
      internal oil phase in a aqueous solution of 3.0 wt% Tween 20 prior to
      emulsification into an external oil phase. The multiple emulsions appeared to be
      stable enough in the presence of HPC polymer in the external oil phase. In sol
      gel reaction, the hydrolysis and condensation rate of TEOS were greatly dependent
      upon the catalyst and the molar ratio of H(2)O to TEOS (R(W)). In this study,
      sphere-like microspheres entrapping retinol were best formed with the addition of
      NH(4)OH as a catalyst when the concentration of TEOS was at the R(W) value of 4.
      Microspheres obtained under these conditions were 15-40 &mgr;m with very dense
      surfaces containing a few globules 1.17-2.35 &mgr;m. Also, they showed the slower
      release of retinol into the external ethanol phase and higher loading and
      encapsulation efficiency. Copyright 2001 Academic Press. 

PMID- 11446790
TI  - A Light Scattering Study of the Transition Region between Diffusion- and Reaction
      Limited Cluster Aggregation.
AB  - Two limiting regimes for colloidal particle aggregation are well described in the
      literature: diffusion-limited cluster aggregation and reaction-limited cluster
      aggregation. Between these two limiting regimes, a vast transition region is
      expected. In this paper, the transition region is studied by means of static and
      dynamic light scattering. Therefore, a system of latex particles is aggregated at
      different electrolyte concentrations. The time dependence of the average
      diffusion coefficient is fitted considering the Brownian kernel and the kernel
      proposed by Schmitt et al. [Phys. Rev. E 62, 8335 (2000)]. The first fits the
      experimental data only at high electrolyte concentrations while the latter, which
      considers multiple cluster-cluster contacts, is found to fit the complete set of
      experimental data. Copyright 2001 Academic Press. 

PMID- 11446791
TI  - Quaternary Ammonium Salts Immobilized on Silica Gel: Exchange Properties and
      Application as Potentiometric Sensor for Perchlorate Ions.
AB  - Ammonium chlorides immobilized on silica gel, SA(+)/Cl(-) and SE(+)/Cl(-), were
      obtained from silica previously modified with 3-aminopropyltriethoxysilane and N
      [3-(trimethoxysilyl)-propyl]ethylenediamine, respectively. Both materials showed
      potential use as an anion exchanger: they are thermically stable (up to 413 K),
      achieve equilibrium rapidly in the presence of suitable exchanger ions, and are
      easily recovered. The exchange capacities observed for SA(+)/Cl(-) and SE(+)/Cl(
      ) are 0.70 and 1.19 mmol Cl(-) g(-1), respectively. Through the exchange
      isotherms and competitive Cl(-)-X(-) exchange (X(-)=F(-), Br(-), I(-), N(3)(-),
      NO(3)(-), SCN(-), ClO(4)(-)) it was observed that: (i) SE(+)/Cl(-) exchanges the
      counterion Cl(-) more easily than SA(+)/Cl(-); (ii) SA(+)/Cl(-) presents higher
      selectivity than SE(+)/Cl(-); and (iii) SA(+)/Cl(-) presents high affinity for
      ClO(4)(-). Because of these two latter properties presented by the SA(+)/Cl(-),
      the derivative SA(+)/ClO(4)(-) was used as a potentiometric sensor for this
      anion, prepared from the supported material on a mixture of graphite powder with
      epoxy resin. The electrode showed a nernstian behavior and a limit of response of
      0.13 mmol L(-1). Potentiometric selectivity coefficients, K(pot)(A, B), were
      obtained for some interfering anions, and the following interference order was
      observed: F(-) > SCN(-) > NO(3)(-) > Br(-) > Cl(-) > CH(3)COO(-). The electrode
      showed fast and stable responses and was useful for approximately 200 measures.
      Copyright 2001 Academic Press. 

PMID- 11446792
TI  - Stability of Liquid Films Containing Monodisperse Colloidal Particles.
AB  - Thin liquid films containing colloidal particles are considered to be the key
      structural elements of three-phase foams containing liquid, gas, and colloidal
      particles. This study is aimed at understanding the stability of such films in
      the absence of any surfactants. The particles form a layered structure in the
      film and produce a stepwise thinning in the thin liquid films. We report here for
      the first time the effects of particle concentration and size on film thickness
      transition of curved liquid films containing monodispersed colloidal particles.
      The rate of stepwise film thinning was observed to be high when particle
      concentration was low and both particle size and film size were large. The
      phenomenon of stepwise film thinning (i.e., stratification) is rationalized on
      the basis of diffusion of colloidal particles from the film to the meniscus,
      i.e., the diffusive osmotic mechanism. There exists a critical film size below
      which at least one layer of particles always stays in the film (i.e., black spot
      expansion does not occur). This critical size is dependent upon both particle
      size and concentration. Also, Monte Carlo simulations of the film show that, at a
      high particle concentration, better particle in-layer structure develops that
      increases the energy barrier, inhibiting particle diffusion from the film to the
      bulk meniscus. Copyright 2001 Academic Press. 

PMID- 11446793
TI  - The Effect of pH on Monoglyceride-Caseinate Mixed Monolayers at the Air-Water
      Interface.
AB  - The surface pressure (pi) area (A) isotherms and Brewster angle microscopy (BAM)
      of monoglyceride-caseinate mixed films spread on buffered water at pH 5 and 7 and
      at 20 degrees C were determined as a function of the mass fraction (X) of
      monoglyceride (monopalmitin or monoolein) in the mixture. The structural
      characteristics, miscibility, and morphology of monoglyceride-caseinate mixed
      films are very dependent on surface pressure and monolayer composition. The
      monolayer structure was more expanded as the pH and the monoglyceride
      concentration in the mixture were increased. From the concentration and surface
      pressure dependence on excess area, free energy, and collapse pressure, it was
      deduced that, at a macroscopic level, monoglyceride (either monopalmitin or
      monoolein) and caseinate form a practically immiscible monolayer at the air-water
      interface. The BAM images and the evolution with the surface pressure of the
      relative reflectivity of BAM images give complementary information on the
      interactions and structural characteristics of monoglyceride-caseinate mixed
      monolayers, which at a microscopic level corroborated in part the conclusions
      derived from the pi-A isotherm at a macroscopic level. Over the overall range of
      existence of the mixed film the monolayer presents some heterogeneity due to the
      fact that domains of monoglyceride (especially of monopalmitin) and spots of
      collapsed caseinate residues are present during the monolayer compression
      expansion cycle, giving relative intensity peaks with high relative film
      thickness. At higher pi, after the caseinate collapse, characteristic squeezing
      out phenomenon was observed. At the monoglyceride monolayer collapse the mixed
      film is practically dominated by the presence of monoglyceride. The prevalence of
      monoglyceride in the interface increases with the amount of monoglyceride in the
      mixture and at higher pi. However, some degree of interactions exists between
      monoglyceride and caseinate in the mixed film and these interactions are more
      pronounced as the monolayer is compressed at the highest surface pressures.
      Copyright 2001 Academic Press. 

PMID- 11446794
TI  - Zeta Potential of Insoluble Monolayer of Long-Chain Alcohol at the Air-Aqueous
      Solution Interface.
AB  - The zeta potential of a close-packed insoluble monolayer of 1-hexacosanol at the
      air-water interface in the presence of 0.001 M NH(4)NO(3) was measured as a
      function of pH by means of the plane interface technique. The negative zeta
      potential increased with the increase of pH up to about 9. The negative charge at
      the monolayer-water interface is considered to be due to the dissociation of
      protons from hydrated alcohol water clusters at the surface. The zeta potential
      results were analyzed in terms of the site dissociation and site-binding
      mechanism within the Gouy-Chapman-Stern-Grahame double-layer model of the metal
      oxide-water interface. Copyright 2001 Academic Press. 

PMID- 11446795
TI  - Crystal Orientation of Hydroxyapatite Induced by Ordered Carboxyl Groups.
AB  - Hydroxyapatite (HAp) crystals were grown from simulated body fluid (SBF) onto the
      arachidic acid monolayers with carboxyl groups, which were prepared by the
      Langmuir-Blodgett (LB) method on substrates. From X-ray diffraction patterns,
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), and
      infrared spectra, it was concluded that the crystalline phase nucleated on the LB
      monolayers was HAp, which was induced by the monolayer because no crystalline
      materials were grown on substrates without a monolayer. According to SEM and TEM
      observations, HAp precipitates were hemispherical aggregates consisting of the
      plate-like crystallites whose specific {100} surfaces were well developed. The
      HAp crystallites were preferentially oriented with their c-axes in a specific
      direction parallel to the substrate near the inorganic/organic interface, which
      suggests the control of the crystallographic orientation in HAp by the aligned
      carboxyl groups in the LB monolayer. Copyright 2001 Academic Press. 

PMID- 11446796
TI  - A New Population Balance Model for Crystal Size Distributions: Reversible, Size
      Dependent Growth and Dissolution.
AB  - A new approach to crystal growth and dissolution, based on a population balance
      equation (PBE) similar to models of reversible chain polymerization, describes
      reversible solute addition to crystal surfaces. The PBE, in combination with a
      mass balance for solute, can be solved for mass moments of the crystal size
      distribution (CSD). The first three moments provide the number, average mass, and
      CSD variance, which allow representation of the CSD by two-parameter, normalized
      statistical distributions, such as lognormal or gamma distributions. With
      realistic initial conditions, operating parameters, and rate coefficients, the
      new theory describes crystal growth, dissolution, and recrystallization (Ostwald
      ripening) processes. Size-dependent interfacial energy affects solubility and
      nucleation and determines the driving force for growth or dissolution. Because
      the model is reversible, the CSD evolves appropriately to equilibrium. The moment
      equations are readily solved and show properties consistent with observed crystal
      growth behavior. Copyright 2001 Academic Press. 

PMID- 11446797
TI  - Thermal and Structural Behavior of Milk Fat.
AB  - Milk fat crystallization was studied using X-ray diffraction as a function of
      temperature (XRDT) and differential scanning calorimetry (DSC) analysis
      considering crystals formed during slow cooling of natural milk fat globules of
      cream. During cooling at |dT/dt|=0.15 degrees C/min from 55 to -8 degrees C, the
      crystalline varieties formed in fat globules by triacyglycerols (TGs) correspond
      to two double-chain-length organizations (2L) of 46.5 and 40 A and to two triple
      chain-length stackings (3L) of 71.3 and 65 A. Nucleation occurs in the alpha
      form; then the alpha+beta' polymorphic forms coexist until the end of the
      cooling. The four crystalline varieties start to form within a 10 degrees C
      range, from about 21 degrees C, preventing separation of overlapped peaks by DSC
      recording. In a second step, the sample of cream was heated at 2 degrees C/min in
      the range -8 to +60 degrees C to follow the melting behavior of the crystals.
      XRDT measurements show the progressive transformations of the crystalline
      varieties correlated with endotherms and exotherms recorded by DSC. The 40-A
      structure takes advantage of the melting of the other species to grow until its
      melting. The comparison made with anhydrous milk fat behavior under the same
      conditions shows that crystallization is different in emulsion and in bulk.
      Copyright 2001 Academic Press. 

PMID- 11446798
TI  - Ionic Environmental Effect on the Time-Dependent Characteristics of Membrane
      Potential in a Bipolar Membrane.
AB  - The membrane potential characteristics of a bipolar membrane are discussed in an
      examination of the contribution of an intermediate phase to time-dependent
      behavior. Bipolar membranes, which consist of a poly(sulfone) base polymer with a
      quaternary amino group and a poly(styrene-co-divinylbenzene) cation-exchange
      membrane, were prepared in this study. The membrane potentials in various
      external concentration differences, the facing directions of the membrane, and
      the external electrolyte solutions were measured as a function of time. In this
      study, the time course of the membrane potential was simulated by using the
      equation based on the Teorell-Meyer-Sievers theory and by assuming the
      concentration in the intermediate phase, which is much higher or lower than that
      in the external solution. The membrane facing direction and the intermediate
      phase condition will alter the direction of the membrane potential change. The
      intermediate phase in a bipolar membrane seems to act as an alteration barrier
      for the membrane potential according to the membrane facing direction. Copyright
      2001 Academic Press. 

PMID- 11446799
TI  - A Preliminary Study of the Spreading of AKD in the Presence of Capillary
      Structures.
AB  - There may be several mechanisms at work in the process of migration or
      redistribution of alkyl ketene dimers (AKD) on cellulose fiber surfaces during
      paper sizing and curing. This work is the second part of a continuing
      investigation of the spreading behavior of AKD on the surfaces of hydrophilic
      substrates. Paper sheets, single cotton, and cotton lint fibers and smooth
      cellulose film were used as substrates. These represent samples that have pores,
      V-shaped grooves, and no capillary structure at all. A very simple and effective
      testing method for studying the AKD migration behavior through these substrates
      was designed. AFM was used to study the surface capillary structures of cotton
      and cotton lint fibers. The results of this study provide hard evidence
      supporting our finding that capillary structures in the form of either interfiber
      pores in a paper sheet or V-shaped grooves on the surface of single fibers are
      essential in order for the spreading of molten AKD on a cellulose substrate to
      occur. Some preliminary results on the existence and the surface diffusion of an
      autophobic precursor of AKD are also presented. The results support the
      conclusion we reached in the first part of this investigation; i.e., the molten
      AKD wets but does not spread on smooth, capillary-free hydrophilic surfaces such
      as glass and cellulose. The driving force from interfacial energy alone does not
      cause spontaneous "flow-like" spreading of molten AKD on these surfaces. This is
      possibly associated with the formation of an autophobic precursor in front of an
      AKD droplet. The results in this study do not support the perception that molten
      AKD forms a single molecular layer on the surface of cellulose fibers by
      spreading during heat treatment, although the autophobic precursor in front of an
      AKD droplet could theoretically be of a monolayer thickness and the surface
      diffusion of this precursor may contribute to the sizing development after heat
      treatment. Copyright 2001 Academic Press. 

PMID- 11446800
TI  - Effect of an ac Perturbation on the Electroosmotic Behavior of a Cation-Exchange
      Membrane. Influence of the Cation Nature.
AB  - The effect of an ac sinusoidal perturbation of known amplitude and frequency
      superimposed on the usual dc applied electric voltage difference on the
      electroosmotic flow through a typical cation-exchange membrane has been studied
      using different monovalent electrolytes. As a general trend, the presence of the
      ac perturbation increases the value of the electroosmotic flow with respect to
      the value in the absence of ac perturbation. A dispersion of the electroosmotic
      permeability on the frequency of the applied ac signal has been found for the
      three studied electrolytes, observing that the electroosmotic permeability
      reaches maximum values for some characteristic values of the frequency. This
      behavior may be related to the different relaxation processes in heterogeneous
      mediums. Copyright 2001 Academic Press. 

PMID- 11446801
TI  - Characterization of Macroscopic Structural Disorder in Porous Media Using Mercury
      Porosimetry.
AB  - A new structural model for the interpretation of mercury porosimetry data for
      samples having a bimodal pore size distribution is presented. The morphology of
      the macropore network of a porous solid has been studied using a combination of
      mercury porosimetry and NMR techniques. The model consists of a lattice-based
      network of pore bodies and pore necks. The model enables assessment of the
      spatial geometric distribution of the directly accessible macropore network of a
      porous material having a bimodal pore size distribution. A methodology that can
      be used to determine the spatial distribution of the critical pore neck diameters
      controlling access to the macroporous void space has also been described. This
      method was used to provide a map of the local critical macropore neck
      distribution over macroscopic length scales for an alumina tablet that is not
      possible with other techniques. Copyright 2001 Academic Press. 

PMID- 11446802
TI  - X-Ray Scattering Investigation of Swelling Clay Fabric.
AB  - The solid phase geometry of a Na- and Ca-montmorillonite has been investigated by
      using ultra-small- and small-angle X-ray scattering and X-ray diffraction. The
      scattering domain covered by combining these techniques corresponds to
      characteristic distances ranging from a few angstroms to a micrometer. The
      intensity scattered on the whole scattering domain was decomposed into two terms,
      (i) one assigned to the structure of layers' stacks and (ii) one ascribed to the
      porous network resulting from the entanglement of individual platelets. The
      comparison of experimental data with theoretical simulations revealed that the
      stacks of clay layers are complex and heterogeneous. Ordered stacks of
      approximately 10 layers separated by 9.5 A seem to be organized in larger
      particles comprising around 100 layers. Distances between 25 and 150 A were
      observed within those particles. Both samples possess a low pore volume fraction
      of about a few percent, with pores characterized by a highly anisotropic shape.
      Copyright 2001 Academic Press. 

PMID- 11446803
TI  - Adsorption and Phase Transitions in Slit-like Pores with Differently Adsorbing
      Walls.
AB  - We study the adsorption of a lattice gas in a slit-like pore with different
      walls. The density profiles are evaluated in the framework of the mean-field
      approximation. We show that changes in the potential field exerted by one wall
      can lead to substantial modifications of the phase behavior of the fluids.
      Copyright 2001 Academic Press. 

PMID- 11446804
TI  - Adsorption and Thermogravimetric Studies of Mesoporous Silica Coated with
      Siloxane Polymer.
AB  - Nitrogen adsorption and high-resolution thermogravimetry were used to study a
      series of samples prepared by coating porous silica with different amounts of
      siloxane polymer. Thermogravimetry was employed to investigate the thermal
      behavior of the coated samples as well as the polymer-silica interactions.
      Nitrogen adsorption was used to monitor the changes in the specific surface area,
      porosity, and surface properties upon polymer coating. It is shown that the
      gradual changes in the aforementioned properties are observed up to some limiting
      coating level. Also, in this coating range a rather uniform film is formed by
      siloxane polymer on the silica surface. Copyright 2001 Academic Press. 

PMID- 11446805
TI  - Thermodynamics Data of Interaction of Copper Nitrate with Native and Modified
      Chrysotile Fibers in Aqueous Solution.
AB  - The interactions involving chrysotile (CRIO) and propylamine (CRI1), and
      propyethylenediamine (CRI2) chrysotiles with copper nitrate in aqueous solution
      were followed through a calorimetric titration technique. The net thermal effects
      were calculated after subtracting the respective thermal effect of dilution for
      all systems. The degree of adsorption gave the order CRI0 < CRI1 < CRI2. The
      mechanism of reaction for copper/chrysotile interaction is due to the ion
      exchange between the H(+) of the external hydroxyl groups of the inorganic
      matrix, which is covered by the presence of 0.26 mmol g(-1) of basic sites on
      fibers. On the other hand, the interactions on modified chrysotile can be
      associated to complex formation with the free pendant amine groups. The enthalpy
      of these processes gave the following values: -4.25+/-0.27, 19.47+/-0.60, and 
      26.55+/-0.16 kJ mol(-1) for CRI0, CRI1, and CRI2 systems, respectively. The
      different behavior of propylamine chrysotile indicated that the hydration effect
      is more pronounced than complex formation. The free Gibbs energy values are in
      agreement with favorable processes. The high entropic values for CRI1 and CRI0
      indicated that the adsorption occurs by entropic reasons, while on CRI2 the
      enthalpic contribution is more pronounced. Copyright 2001 Academic Press. 

PMID- 11446806
TI  - Synthesis and Characterization of Basic Catalysts Based on Sodium-Magnesium Mixed
      Phosphates and Their Use in the Conversion of 2-Hexanol.
AB  - Various catalysts consisting of sodium-magnesium mixed orthophosphates were
      synthesized and characterized in structural terms using X-ray diffraction,
      thermogravimetric analysis, differential thermal analysis, diffuse reflectance
      infrared spectroscopy, and solid-state (31)P NMR spectroscopy. In addition, the
      surface properties of the solids were determined from N(2) adsorption-desorption
      isotherms and their chemical properties characterized with various titrants. One
      of the solids obtained consists of NaMgPO(4)/Mg(2)P(2)O(7) and the rest of
      NaMgPO(4)/MgO. Their surface chemical properties vary depending on the particular
      synthetic procedure used; thus, the NaMgPO(4)/MgO systems exhibit similar
      populations of acid and basic sites, whereas the NaMgPO(4)/Mg(2)P(2)O(7) systems
      contain many more acid sites than basic sites. All the solids obtained exhibit
      substantial dehydrogenating activity in the conversion of gaseous 2-hexanol; in
      fact, some of the NaMgPO(4)/MgO systems are even more active and selective than a
      MgO solid tested under identical reaction conditions. Copyright 2001 Academic
      Press. 

PMID- 11446807
TI  - Modification of the Interlayer Surface of Layered Copper(II) Hydroxide Acetate
      with Benzoate Groups: Submicrometer Fiber Generation.
AB  - We report on the functionalization of layered copper(II) hydroxide acetate with
      benzoic acid. The grafting of benzoate groups is characterized by
      thermogravimetry/differential scanning calorimetry, Fourier transform infrared
      spectroscopy, and X-ray photoelectron spectroscopy. The submicrometer fiber
      generation of the grafted material is clearly demonstrated through scanning
      electron microscopy. Copyright 2001 Academic Press. 

PMID- 11446808
TI  - Surface Chemistry of Activated Carbons: Combining the Results of Temperature
      Programmed Desorption, Boehm, and Potentiometric Titrations.
AB  - Three samples of activated carbon were used for this study: two of wood and one
      of coal origin. The samples were further oxidized to study the effect of
      oxidation on the surface chemistry. The surface chemistry was characterized by
      using Boehm and potentiometric titrations, temperature-programmed desorption
      (TPD), and DRFTS. The results showed that oxidation introduces a variety of
      functional groups to the surface, making it more heterogeneous. Titration methods
      provide comparable results, whereas TPD detects more oxygen-containing groups.
      Discrepancies in the obtained results are due to limitations of the titration
      methods where only acidic and basic sites of certain strength can be detected. On
      the other hand, TPD can assess all functional groups but with less quantitative
      information. Moreover, comparison of TPD and titration methods leads to the
      detection of functional groups containing atoms other than oxygen and carbon as,
      for instance nitro groups, introduced to the carbon matrix via the nitration
      mechanism during oxidation with HNO(3). Copyright 2001 Academic Press. 

PMID- 11446809
TI  - Steady Vapor Bubbles in Rectangular Microchannels.
AB  - We consider vapor bubbles in microchannels in which the vapor is produced by a
      heater element and condenses in cooler parts of the interface. The free boundary
      problem is formulated for a long steady-state bubble in a rectangular channel
      with a heated bottom. Lubrication-type equations are derived for the shape of the
      liquid-vapor interface in a cross-sectional plane and in the regime for which the
      vapor phase fills most of the cross section. These equations are then solved
      numerically over a range of parameter values with given temperature profiles in
      the walls and subject to a global integral condition requiring evaporation near
      the heater to balance condensation in colder areas of the interface. Our results
      show that depending on the temperature, the side walls can be either dry or
      covered with a liquid film and we identify criteria for these two different
      regimes. The asymptotic method breaks down in the limit when capillary
      condensation becomes important near the bubble top and a different approach is
      used to determine the shape of the bubble in this limit. Solutions here involve
      localized regions of large mass fluxes, which are asymptotically matched to
      capillary-statics regions where the heat transfer is negligible. Copyright 2001
      Academic Press. 

PMID- 11446810
TI  - The Behavior of Sorbitan Surfactants at the Water-Oil Interface: Straight-Chained
      Hydrocarbons from Pentane to Dodecane as an Oil Phase.
AB  - The interfacial tension of four sorbitan surfactants (Span 20, sorbitan
      monolaurate; Span 40, sorbitan monopalmitate; Span 60, sorbitan monostearate; and
      Span 80, sorbitan monooleate) was determined at the water-oil interface. Seven
      straight-chained hydrocarbons from pentane to dodecane were used as an oil phase.
      From the interfacial tension measurements the following values were calculated:
      critical micelle concentration (cmc), the interfacial tension at the cmc
      (gamma(cmc)), surface pressure at the cmc (pi(cmc)), area per molecule at the cmc
      (A(cmc)), standard free energy of micellization (DeltaG degrees (mic)), and
      standard free energy of adsorption (DeltaG degrees (ad)). The shorter chained
      Span 20 and unsaturated Span 80 had higher cmc values and Span 80 had a larger
      molecular area than the other surfactants. With the same oil phase, differences
      between pi(cmc) values of the four sorbitan monoesters were small, but the
      gamma(cmc) was slightly lowered as the hydrophobicity of the surfactant was
      increased. DeltaG degrees (mic) was less negative for Span 20 and the DeltaG
      degrees (ad) value was slightly more negative for Span 80. The effect of the oil
      phase was obvious. Increasing the hydrocarbon chain length of the oil phase
      increased gamma(cmc) and cmc values while pi(cmc) and A(cmc) were decreased. As
      the length of the hydrocarbon chain of the oil phase was increased, DeltaG
      degrees (mic) and DeltaG degrees (ad) became less negative, which means a less
      spontaneous reaction. Copyright 2001 Academic Press. 

PMID- 11446811
TI  - Critical Micelle Concentrations of Nonionic Surfactants in Organic Solvents:
      Approximate Prediction with UNIFAC.
AB  - The objective of this study was to model the critical micelle concentration (cmc)
      of nonionic surfactants in nonaqueous systems using the UNIFAC group contribution
      method. For the prediction of the cmc the phase separation approach was used,
      where the micellar phase is approximated as a second liquid phase resulting from
      the liquid-liquid equilibrium between the solvent and the surfactant, with the
      necessary activity coefficients predicted by UNIFAC. The limited amount of
      literature data for reverse micelle formation in nonaqueous systems was used to
      test the predictions, varying surfactant type, solvent, and temperature. The most
      promising model was the modified UNIFAC of B. L. Larsen, P. Rasmussen, and A.
      Fredenslund (Ind. Eng. Chem. Res. 26, 2274 (1987)). Since most nonionic
      surfactants contain oxyethylene chains, a new set of parameters was evaluated for
      this group, leading to satisfactory predictions. The average deviation between
      the predicted and the experimental cmc's was about 0.1 log units. Copyright 2001
      Academic Press. 

PMID- 11446812
TI  - Aggregation Behavior of Nonionic Surfactants Synperonic A7 and A50 in Aqueous
      Solution.
AB  - The aggregation behavior of Synperonic A7 and A50, fatty alcohol ethoxylate
      nonionic surfactants (C(m)E(n)) with mean polyoxyethylene chain lengths of 7 and
      50, respectively, was investigated in aqueous solution by means of surface
      tension, laser light scattering, steady-state fluorescence, and fluorescence
      quenching experiments. Surface tension measurements at room temperature indicate
      that the critical micelle concentration of A7 is 0.1 g/L (0.22 mM) and that of
      A50 is 0.17 g/L (0.07 mM). Static light scattering measurements reveal that the
      averaged aggregation number of A7 in water is 417 and that of A50 is 23. When
      solutions of A7 were allowed to age over a period of months at room temperature,
      the micelle M(w) and hydrodynamic radius increased. The aggregation numbers found
      from fluorescence quenching measurements, using excimer formation from 1
      ethylpyrene as a probe, were about 300 for freshly prepared solutions of A7 and
      about 40 for A50. We also found that the presence of air has a strong effect on
      the data obtained from the fluorescence quenching measurements. Copyright 2001
      Academic Press. 

PMID- 11446813
TI  - Thermodynamics of Unilamellar Vesicles: Influence of Mixing on the Curvature Free
      Energy of a Vesicle Bilayer.
AB  - The influence of mixing on the curvature free energy of a thermodynamically open,
      reversibly formed vesicle bilayer is investigated by deriving expressions for the
      various contributions to the bilayer bending constant k(bi) as functions of the
      structure of aggregated surfactants as well as the solution state (electrolyte
      concentration, average composition in the bilayers, etc). k(bi) is shown to be
      lowered in surfactant mixtures as a result of the fact that a mixed vesicle
      bilayer that is open in the thermodynamic sense may assume different compositions
      in the inner and outer monolayers. The net contribution of all terms related to
      surfactant mixing is to lower k(bi). The magnitude of this reduction increases
      with increasing asymmetry between the two surfactants with respect to charge
      number, head group size, and tail length. The reduction of k(bi) due to mixing is
      most pronounced for mixtures where the surfactant that carries charge or has the
      highest charge number has the larger head group and the smaller tail. Copyright
      2001 Academic Press. 

PMID- 11446814
TI  - The Effect of Surfactant on the Motion of a Buoyancy-Driven Drop at Intermediate
      Reynolds Numbers: A Numerical Approach.
AB  - A numerical investigation of the flow field inside and around a deformed drop
      translating in another quiescent liquid contaminated by surfactant soluble in
      continuous phase but not soluble in dispersed phase is presented in this paper.
      The finite difference method was used to solve numerically the coupled Navier
      Stokes and convective-diffusion equations in a body-fitted orthogonal coordinate
      system. The present numerical simulation of a two-fluid free-boundary problem was
      validated by comparison of the simulation results of a drop contaminated by
      surfactant at creeping flow with the analytical solution and the predicted rise
      velocity of a bubble contaminated by SDS with experimental data at the moderate
      Reynolds number. To evaluate the effect of surfactant on the drag coefficient,
      the steady motion of a drop of the same volume in the pure and contaminated
      systems was simulated. The behavior of the recirculating wake behind a
      contaminated drop was also examined and found that it becomes more closely
      attached to the rear stagnancy of the drop when the surfactant concentration is
      increased gradually. Finally, the stagnant-cap model was revisited and its
      defects and limitations were analyzed against numerical simulation. Copyright
      2001 Academic Press. 

PMID- 11446815
TI  - Apparent Binding Degree of a Counterion and Micellar Composition in Cationic and
      Nonionic Surfactant Mixed Solutions at CMC.
AB  - The Gibbs-Duhem equation of an ionic aggregate is obtained, considering the
      activity coefficient of the aggregate due to the interaction between the
      aggregate ion and its diffusion layer. The equation is applied to mixtures of
      cationic and nonionic surfactants. The critical micelle concentrations of the
      cationic and nonionic surfactant mixtures were measured in the presence of an
      inorganic salt with the same counterion. The logarithm of the CMC of the mixture
      gives a linear relationship versus the logarithm of the counterion concentration
      for a constant molar ratio of the two surfactants. The apparent binding degree of
      the counterion and the fraction of the nonionic surfactant in the mixed micelle
      were obtained from the CMC data using the Gibbs-Duhem equation. The binding
      degree which is obtained by the Corrin-Harkins equation is apparent. The apparent
      binding degree increases with the decrease in the counterion concentration. The
      behavior of the apparent binding degree is different from that of the real
      binding degree obtained by potentiometry. These facts are explained by our
      definition of the apparent binding degree of the counterion. Copyright 2001
      Academic Press. 

PMID- 11446816
TI  - The Change in the Properties of Sodium Dodecyl Sulfate Micelles upon Addition of
      Isomeric and Unsaturated Short-Chain Alcohols Probed by Photophysical Methods.
AB  - The properties of sodium dodecyl sulfate micelles (SDS) in the presence of 1
      propanol, 2-propanol, and 2-propen-1-ol (allyl alcohol) were investigated using
      electrical conductivity and fluorescence quenching methods. The constants of
      association of the alcohols to SDS micelles, obtained experimentally and
      calculated from linear solvation energy relationship analysis, are in the range 1
      2 M(-1), indicating that these additives behave not only as cosolvents but also
      as micellar surface active solutes. Larger molecular volume and lower basicity of
      the alcohol favor partitioning to the micelle. The formation of smaller micelles
      upon addition of the alcohols is accompanied by an enhancement of solute
      intermicellar migration and intramicellar quenching rate constants. In
      particular, the micelle fragmentation-coagulation process of the SDS (0.04
      M)/allyl alcohol (1.5 M) system occurs in the time range of 1.5 &mgr;s, as
      indicated by the intermicellar exchange rate constant of the N-dodecylpyridinium
      ion. Copyright 2001 Academic Press. 

PMID- 11446817
TI  - Experimental Investigation of the Orthokinetic Coalescence Efficiency of Droplets
      in Simple Shear Flow.
AB  - The coalescence efficiency of two droplets in simple shear flow was
      experimentally investigated. The effects of the radius of the colliding droplets,
      the viscosity of the continuous medium, and the radii ratio on the coalescence
      efficiency were studied. The coalescence efficiency was determined from the
      critical angle, alpha(crit), above which the droplets coalesce and below which no
      coalescence takes place. It was found that the coalescence efficiency decreases
      and then increases with the flow number. The theories of the drainage models and
      the trajectory analysis were unable to predict the experimental results. This was
      attributed to the inadequacy of the existing expression used for the critical
      film thickness. On the basis of the experimental data obtained a new expression
      for the critical film thickness was proposed. The new expression predicts a
      decrease followed by an increase in the critical film thickness. The increase in
      the critical film thickness is, perhaps, due to instabilities that take place at
      the interfaces. Implementing the proposed expression for the critical film
      thickness, the experimentally measured coalescence efficiency, the capture angle
      and the contact time were successfully predicted. The experimental investigation
      revealed that the coalescence efficiency does not depend on the radii ratio in
      the range 0.7 to 1. The experimental investigation also showed that the
      coalescence efficiency increases as the viscosity of the continuous phase
      decreases. Measuring the capture angle showed that coalescence can take place
      either in the compression or in the extensional quadrant of the shear plane. A
      variation in the capture angle and the contact time was observed for a given
      fixed set of conditions. The change of the angle alpha with time was measured.
      The measured values were compared to those calculated from an equation derived by
      R. S. Allan and S. G. Mason (J. Colloid Interface Sci. 17, pp. 383, 1962). A good
      agreement was obtained when the droplets were of equal radii and small in size.
      When the droplets were large in size and of different radii, the agreement was
      not satisfactory. Measuring the distance between the centers of the colliding
      droplets showed that the two droplets vibrated when they came close to each
      other. Copyright 2001 Academic Press. 

PMID- 11446818
TI  - Rheological Properties and Stabilization of Magnetorheological Fluids in a Water
      in-Oil Emulsion.
AB  - The rheological properties and dispersion stability of magnetorheological (MR)
      fluids consisting of hydrophilic treated carbonyl iron particles dispersed in a
      water-in-oil emulsion were studied for the first time by the use of a stress
      controlled rheometer and sedimentation test. In order to improve the stability of
      the MR fluids, carbonyl iron magnetic particles were chemisorbed by Tween 80 and
      a water-in-oil emulsion was employed as a continuous phase for MR fluids.
      Attraction between hydrophilic-treated carbonyl iron and water emulsion in
      continuous phase plays a critical role in greatly improving stability of dense
      carbonyl iron particles against sedimentation without restricting rheological
      properties. On application of magnetic fields, the suspensions show a striking
      increase in viscosity. Since constant stress is generated within the limit of
      zero shear rate, the plateau in the flow curve corresponds to the Bingham yield
      stress. Under a low external magnetic field, the yield stress varied as B(3/2),
      indicating that local magnetization saturation occurs between the neighboring
      magnetized particles. The yield stress has an approximately linear relation to
      the particle volume fraction. Copyright 2001 Academic Press. 

PMID- 11446819
TI  - Nonequilibrium Molecular Dynamics Simulations of Steady-State Heat and Mass
      Transport in Condensation. II. Transfer Coefficients.
AB  - We present coefficients for transfer of heat and mass across the liquid-vapor
      interface of a one-component fluid. The coefficients are defined for the Gibbs
      surface from nonequilibrium thermodynamics and determined by nonequilibrium
      molecular dynamics simulations. The main conductivity coefficients are found to
      become large near the critical point, consistent with the disappearance of the
      surface in this limit. The resistivities of transfer found by molecular dynamics
      simulations are compared to the values predicted by kinetic theory. The main
      resistivity to heat transfer is found to agree from the triple point to about
      halfway to the critical point. The resistivity to mass transfer was used to
      determine the condensation coefficient, which was found to be practically
      constant with a value of about 0.82. The resistivity coupling coefficient
      predicted by simulations also agrees with values predicted by kinetic theory from
      the triple point until about halfway to the critical point. Copyright 2001
      Academic Press. 

PMID- 11446820
TI  - Aqueous Solution Properties of Pyridinium-Type Perfluorinated Surfactants and
      Simulation of Mixture CMC.
AB  - The critical micelle concentrations (CMCs) of 1,1,2,2
      tetrahydroperfluoroalkylpyridinium chloride have been determined by measurements
      of surface tension and electrical conductivity, etc. The CMCs of perfluorinated
      surfactants were only about 0.02 times that of hydrocarbon one with the same
      carbon number. Aqueous solutions of fluorocarbon surfactants gave low surface
      tensions in comparison with those of hydrocarbon surfactants. The area per
      surfactant molecule at the air-water interface decreased with increasing length
      of the fluorocarbon chain. Electromotive force measurements were made with
      chloride-responsive electrodes on surfactants solutions. The micelle ionization
      degrees decreased with increasing length of the alkyl chain. The group
      contribution method simulated the mixture CMCs of binary surfactants with various
      alkyl chain lengths. The group contribution method proved to be very useful to
      predict not only the mixture CMCs but also the demixing regions of binary
      mixtures having great differences in CMC. Copyright 2001 Academic Press. 

PMID- 11446821
TI  - Random Trajectory Modeling of Limited-Volume Percolation in a Microporous
      Structure.
AB  - The limited-volume analytical method for the evaluation of the probability of
      percolation (random trajectory approach) is developed. The model uses
      probabilistic analysis of possible percolation ways. The main equation for the
      probability of percolation contains parameters related to the conditions of
      formation of the microporous medium. Results of some computer estimations of the
      influence of various formation-related parameters (porosity, surface tension,
      coordination number, etc.) are presented. Copyright 2001 Academic Press. 

PMID- 11446822
TI  - A Model Substrate for Ellipsometry Studies of Lipoprotein Deposition at the
      Endothelium.
AB  - Endothelial cell layers from umbilical cords were grown on methylated silica
      surfaces. Fluorescence microscopy showed this layer to be confluent and to
      consist of living cells. Initial ellipsometry measurements were performed to
      illustrate both the stability of the model surface in ellipsometry measurements
      and the Ca(2+)-dependent binding of lipoproteins at the cell-based substrate. The
      present substrate holds promise as a model substrate for in vitro investigations
      of lipoprotein deposition at the endothelium surface under close to in vivo
      conditions. Copyright 2001 Academic Press. 

PMID- 11446823
TI  - Enthalpies of Micellization of Double Chain and Gemini Cationic Surfactants.
AB  - Microcalorimetric measurements have been made on double chain cationic
      surfactants with the formula [C(N)H(2N+1)C(M)H(2M+1)N(CH(3))(2)]Br, referred to
      as C(N)C(M)DAB, and a cationic gemini surfactant with the formula
      [C(12)H(25)(CH(3))(2)N(CH(2))(12)N(CH(3))(2)C(12)H(25)]Br(2), referred to as
      C(12)C(12)C(12)Br(2). The CMCs and enthalpies of micellization for the compounds
      C(12)C(6)DAB, C(14)C(4)DAB, C(16)C(2)DAB, and C(12)C(12)C(12)Br(2) are obtained
      from experiments. The effect of the ratio (N/M) of the two alkyl chain lengths
      for the C(N)C(M)DABs on the micellization process has been investigated. The
      contribution of DeltaH(mic) to DeltaG(mic) is about 3.4% at N/M=2, about 11% at
      N/M=3.5 and about 39% at N/M=8, suggesting that when the total carbon atoms (N+M)
      remain constant, the micellization process will be driven by entropy or entropy
      and enthalpy jointly with increasing ratio (N/M). In addition, the comparison
      between C(12)C(12)C(12)Br(2) and its corresponding monomer (C(12)C(6)DAB) is
      interesting. The micellization process for C(12)C(12)C(12)Br(2) is driven jointly
      by enthalpy and entropy, whereas the micellization process for C(12)C(6)DAB is
      driven mainly by entropy. Copyright 2001 Academic Press. 

PMID- 11446824
TI  - Cognitive function and cholinergic neurochemistry in weanling rats exposed to
      chlorpyrifos.
AB  - Previous studies have shown that moderate to high levels of chlorpyrifos (CPF)
      alter cognitive function in adult and immature rats. In the present study, we
      tested the hypothesis that lower-level exposure to CPF before or immediately
      after weaning causes deficits in cognitive function. A total of 78 Long-Evans
      rats were injected subcutaneously with 0, 0.3 or 7.0 mg/kg CPF every 4 days
      before or after weaning and were tested with the Morris swim task from postnatal
      day 24 through 28. Exposure to CPF before weaning did not cause signs of overt
      cholinergic intoxication or impaired growth nor did the exposures cause
      significant inhibition of regional brain cholinesterase (ChE) activity or
      reduction in muscarinic receptors 24 h after the last injection. However, spatial
      learning was impaired after 5 days of training in the group of weanling rats
      administered 7.0 mg/kg CPF. Rats administered 0.3 or 7.0 mg/kg CPF after weaning
      were also impaired in the task, without significant changes in brain ChE
      activity. These data indicate that low-level exposure to CPF caused deficits in
      cognitive function in weanling rats, and these effects did not appear to be
      mediated by the inhibition of brain ChE. It is suggested that the alteration of
      cognitive function in juvenile rats is an important functional correlate of the
      cellular and molecular effects of CPF in the immature brain. The mechanisms for
      CPF-induced cognitive dysfunction are unknown.

PMID- 11446825
TI  - A Bayesian analysis of the influence of GSTT1 polymorphism on the cancer risk
      estimate for dichloromethane.
AB  - The carcinogenicity of dichloromethane (DCM) is related to metabolic activation
      mediated by glutathione transferase theta 1 (GSTT1), whereas oxidation serves as
      a detoxification pathway. The aim of this study was to calculate the excess
      cancer risk from DCM, using Bayesian statistics. In a first step, a previously
      developed population physiologically based pharmacokinetic (PBPK) model for DCM
      was simultaneously fitted to extensive human toxicokinetic data from 27 male
      volunteers exposed to 250-1000 ppm DCM (Astrand et al. Scand. J. Work Environ.
      Health 1, 78-94, 1975; Engstrom and Bjurstrom, Scand. J. Work Environ. Health 7,
      215-224, 1977) using Markov chain Monte Carlo simulation. Improved population
      estimates were obtained for the PBPK model parameters. In a second step, excess
      cancer risk was calculated for lifelong exposure to 1-1000 ppm DCM by Monte Carlo
      simulation. Data on GSTT1 gene frequencies in the Swedish population were used,
      including all three genotypes. Estimated mean and median excess risks were in
      general agreement with those previously derived (El-Masri et al. Toxicol. Appl.
      Pharmacol. 158, 221-230, 1999). However, we estimate higher excess risks at the
      upper confidence limits. Furthermore, our simulations suggest that 1% of the
      Swedish population is not covered by a factor 4.2-7.1 away from the mean target
      dose. The majority of the fraction of the population not covered was classified
      as GSTT1 homozygote. This indicates that a higher uncertainty factor than the
      commonly used 3.16 should be considered in noncancer risk assessment for
      substances with polymorphic bioactivation.

PMID- 11446826
TI  - Involvement of cyclooxygenase-2 in the potentiation of allyl alcohol-induced
      liver injury by bacterial lipopolysaccharide.
AB  - Bacterial endotoxin (lipopolysaccharide; LPS) augments the hepatotoxicity of a
      number of xenobiotics including allyl alcohol. The mechanism for this effect is
      known to involve the inflammatory response elicited by LPS. Upregulation of
      cyclooxygenase-2 (COX-2) and production of eicosanoids are important aspects of
      inflammation, therefore studies were undertaken to investigate the role of COX-2
      in LPS-induced enhancement of liver injury from allyl alcohol. Rats were
      pretreated (iv) with a noninjurious dose of LPS or sterile saline vehicle and 2 h
      later were treated (ip) with a noninjurious dose of allyl alcohol or saline
      vehicle. COX-2 mRNA was determined by semiquantitative reverse transcriptase
      polymerase chain reaction (RT-PCR), and liver injury was assessed from activities
      in serum of alanine and aspartate aminotransferases (ALT and AST, respectively)
      and from histology. Liver injury was observed only in rats cotreated with LPS and
      allyl alcohol. Serum ALT activity was increased by 4 h after administration of
      LPS and continued to increase through 8 h. COX-2 mRNA was detectable at low
      levels in livers from rats receiving only the vehicles at any time up to 8 h.
      Expression of COX-2 mRNA was increased by 30 min after administration of LPS and
      remained elevated through 6 h. Allyl alcohol treatment alone caused an increase
      in COX-2 mRNA at 4 h (2 h after allyl alcohol) that lasted less than 2 h. In
      livers from rats cotreated with LPS and allyl alcohol, levels of COX-2 mRNA were
      greater than levels seen with either LPS or allyl alcohol alone. The increased
      expression of COX-2 mRNA was accompanied by an increase in the concentration of
      prostaglandin (PG) D(2) in plasma. Plasma PGD(2) concentration was increased to a
      greater extent in rats treated with LPS plus allyl alcohol compared to allyl
      alcohol or LPS alone. Pretreatment with the COX-2 selective inhibitor, NS-398,
      abolished the increase in plasma PGD(2) and reduced the increase in ALT and AST
      activities observed in rats cotreated with LPS and allyl alcohol. NS-398 did not
      affect liver injury from allyl alcohol alone administered at a larger,
      hepatotoxic dose. In addition, ibuprofen, a nonselective inhibitor of
      cyclooxygenases, did not protect against liver injury from LPS plus allyl
      alcohol. In isolated hepatocytes PGD(2), but not PGE(2), reduced the
      concentration of allyl alcohol required to cause half-maximal cytotoxicity. These
      results suggest that products of COX-2 play a role in the augmentation of allyl
      alcohol-induced liver injury by LPS.

PMID- 11446827
TI  - Mechanism of urinary tract crystal formation following biphenyl treatment.
AB  - Coadministration of biphenyl and KHCO3 in the diet of male rats for 13 weeks
      produced urine crystals, which, by means of LC-MS/MS analyses, were determined to
      be composed of the potassium salt of 4-hydroxy-biphenyl-O-sulfate (4-HBPOSK).
      Biphenyl alone or biphenyl with KCl or NaHCO3 in the diet did not produce urine
      crystals. It was found that the higher concentration of potassium in the urine
      and the alkaline pH induced by feeding KHCO3 to rats resulted in the formation of
      urine crystals of 4-HBPOSK due to 4-HBPOSK solubility being lower in urine than
      in plasma. Urine crystals of 4-HBPOSK produced hyperplasia of the transitional
      epithelium of the ureter, ureteral obstruction, and hydronephrosis in the urinary
      tract.

PMID- 11446828
TI  - Arsenic induces apoptosis in rat cerebellar neurons via activation of JNK3 and
      p38 MAP kinases.
AB  - Primary cultures of rat cerebellar neurons were used to study mechanisms of
      arsenic neurotoxicity. Exposure to 5, 10, or 15 microM sodium arsenite reduced
      cerebellar neuron viability and induced nuclear fragmentation and condensation as
      well as DNA degradation to oligonucleosome fragments. Exposure to 1 or 5 mM
      dimethylarsinic acid caused similar changes. Therefore, both inorganic arsenite
      and organic dimethylarsinic acid induce apoptosis in cerebellar neurons, with the
      inorganic form being more toxic. Cotreatment with cycloheximide or actinomycin D,
      inhibitors of protein or RNA synthesis, respectively, or with the caspase
      inhibitor zVAD, completely blocked arsenite-induced cerebellar neuron apoptosis.
      This implies that arsenite-induced cerebellar neuron apoptosis requires new gene
      expression and caspase activation. Interestingly, sodium arsenite selectively
      activated p38 and JNK3, but not JNK1 or JNK2 in cerebellar neurons. Blocking the
      p38 or JNK signaling pathways using the inhibitors SB203580 or CEP-1347 protected
      cerebellar neurons against arsenite-induced apoptosis. These data suggest that
      arsenite neurotoxicity may be due to apoptosis caused by activation of p38 and
      JNK3 MAP kinases.

PMID- 11446829
TI  - Pharmacokinetic studies in Tg.AC and FVB mice administered [14C] benzene either
      by oral gavage or intradermal injection.
AB  - Chronic benzene toxicity has been demonstrated to result in either aplastic
      anemia or acute myelogenous leukemia, a form of granulocytic leukemia, in exposed
      people (Snyder and Kalf, Crit. Rev. Toxicol. 24, 177-209, 1994). Aplastic anemia
      has been demonstrated in animal models following benzene exposure but,
      heretofore, it has not been possible to replicate benzene-induced granulocytic
      leukemia in animals. The Tg.AC mouse appears to be the first animal model in
      which a granulocytic leukemia was produced by treatment with benzene (Tennant et
      al., The Use of Short- and Medium-Term Tests for Carcinogenic Hazard Evaluation,
      1999; French and Saulnier, J. Toxicol. Environ. Health 61, 377-379, 2000).
      Leukemia was observed in Tg.AC mice to which benzene was administered dermally.
      Neither orally dosed Tg.AC mice or mice of the parental FVB strain treated by
      either route of exposure developed leukemia. It is well established that benzene
      metabolism is required to produce benzene toxicity. To determine whether
      metabolic differences arising from differences in route of exposure or strain of
      mouse directed the development of leukemia, the pharmacokinetics of benzene were
      compared between the two strains and between the two routes of administration.
      Regardless of the route of exposure or the strain of mouse, seven major
      metabolites plus unmetabolized benzene were detected in most samples at most time
      points. Few differences were observed between the two strains following either
      route of administration. These results suggest that the genetic modification in
      the Tg.AC mouse, i.e., insertion of the v-Ha-ras construct into the genome, did
      not disrupt any major pathways involved in determining the pharmacokinetics of
      benzene. Two significant differences were observed between the two routes of
      exposure: first, benzene was absorbed more slowly after intradermal injection
      than after oral gavage, and second, the intradermally dosed mice produced more
      conjugates of hydroquinone than did the orally dosed mice. These differences in
      metabolism may be involved in the previously observed differences in
      hematotoxicity between the two routes of exposure.

PMID- 11446830
TI  - The synergistic upregulation of phase II detoxification enzymes by glucosinolate
      breakdown products in cruciferous vegetables.
AB  - Cruciferous vegetables contain secondary metabolites termed glucosinolates that
      break down to products that upregulate hepatic detoxification enzymes. We have
      previously shown that a mixture of four major glucosinolate breakdown products
      from Brussels sprouts interact to produce synergistic induction of phase II
      detoxification enzymes. Here we tested the hypothesis that this synergism is at
      the level of transcription and is due to the interaction between the oral
      bifunctional inducer, indole-3-carbinol (I3C), and monofunctional inducer,
      crambene (1-cyano 2-hydroxy 3-butene). Adult male rats were treated by gavage
      with either corn oil (vehicle); crambene (50 mg/kg), I3C (56 mg/kg), or a mix of
      crambene and I3C at the doses shown. Given orally, I3C alone and crambene with
      I3C caused significant induction of CYP1A activity and CYP1A1 mRNA levels,
      whereas crambene alone had no significant effect on CYP1A activity or mRNA
      levels. Crambene and I3C individually caused induction of glutathione S
      transferase (GST) and quinone reductase (QR) activity. The mixture of crambene
      and I3C caused induction of GST and QR that was significantly greater than the
      sum of the induction by individual treatments. Upregulation of total GST activity
      was not as great as that of QR, possibly because some subunits did not show this
      effect. GST Ya2 mRNA showed a synergistic upregulation by crambene and I3C, while
      Yc1 and Yc2 showed only an additive response. We speculate that this different
      regulation is partly due to differences in gene sequences within the antioxidant
      response element and xenobiotic response element in the regulatory region of GST
      Ya2 compared to those within the regulatory region of the Yc1/Yc2 subunits.

PMID- 11446831
TI  - The synthetic retinoid AGN 193109 but not retinoic acid elevates CYP1A1 levels in
      mouse embryos and Hepa-1c1c7 cells.
AB  - The synthetic retinoid AGN 193109 is a potent pan retinoic acid receptor (RAR)
      antagonist. Treatment of pregnant mice with a single oral 1 mg/kg dose of this
      antagonist on day 8 postcoitum results in severe craniofacial (median cleft face
      or frontonasal deficiency) and eye malformations in virtually all exposed
      fetuses. Using differential display analysis, we have determined that CYP1A1 mRNA
      levels are elevated in mouse embryos 6 h following treatment with AGN 193109.
      Similarly, an elevation in CYP1A1 mRNA levels, protein levels, and aryl
      hydrocarbon hydoxylase activity occurs in Hepa-1c1c7 cells, with the maximal
      elevation observed when the cells were treated with 10(-5) M AGN 193109 for 4 to
      8 h. Elevation in CYP1A1 mRNA levels in mouse embryos and Hepa-1c1c7 cells does
      not occur upon treatment with the natural retinoid, all-trans-retinoic acid.
      Finally, elevation in CYP1A1 mRNA levels was not observed when mutant Hepa-1c1c7
      cells, which are defective in either the aryl hydrocarbon receptor (AhR) or aryl
      hydrocarbon receptor nuclear translocator (ARNT), were treated with AGN 193109.
      This suggests that the AhR/ARNT pathway and not the RAR/RXR pathway is mediating
      the elevation of CYP1A1 mRNA levels by AGN 193109, at least in the Hepa-1c1c7
      cells. This is the first example of a retinoid that displays the abililty to
      regulate both the RAR/RXR and AhR/ARNT transcriptional regulatory pathways.

PMID- 11446832
TI  - Evidence for endocrine disruption in perch (Perca fluviatilis) and roach (Rutilus
      rutilus) in a remote Swedish lake in the vicinity of a public refuse dump.
AB  - A two-year study on perch (Perca fluviatilis) in Lake Molnbyggen, Sweden, located
      in a pristine area but with a public refuse dump in the vicinity, has been
      conducted. The mechanistic approach through a set of biomarkers during the first
      year included age, condition, somatic growth, liver, gonad, and spleen weights,
      and a number of other physiological variables, in addition to ethoxyresorufin O
      deethylase, glutathione-S-transferase, glutathione reductase, catalase, and the
      formation of DNA adducts in the liver. Perch from the uncontaminated Lake
      Djursjon, located in a neighboring drainage area, were used as reference fish.
      The most pronounced effect was a 80% reduction in the gonadosomatic index (GSI)
      for females and a corresponding 36% reduction in males. Fin erosion and shallow
      open sores were also frequently observed. Biomarkers and later chemical analysis
      employed indicated that exposure to well-known environmental pollutants was low,
      suggesting that less well-known antrophogenic substances are responsible for the
      effects observed in perch from Lake Molnbyggen. During the second year, roach
      (Rutilus rutilus) of both sexes were also included in this study. In addition,
      aromatase (P450arom) activity in the brain and testosterone and 17beta-estradiol
      levels in blood plasma were analyzed. Only one-fourth of the female perch were
      found to be sexually mature, which was associated with decreased GSI, lower
      P450arom activity, and reduced circulating levels of steroids. The reproductive
      disorders observed indicates disturbed endocrine function(s), arresting the
      majority of the female perch in a sexually nonreproducible immature stage. This
      novel study is the first to report evidence for endocrine disruption in wild
      populations of fish living in a lake exposed to leakage water from a public
      refuse dump.

PMID- 11446833
TI  - Effects of methylmercury and organic acid mercurials on the disposition of
      exogenous selenium in rats.
AB  - Interaction of methylmercury (MM), an environmental and industrial toxicant, with
      selenium is well known but incompletely understood. Therefore, the effects of MM
      (10 micromol/kg i.v.) on the disposition of exogenous selenium were compared with
      those of other organic mercurials (merbromine, mercuribenzene sulfonic acid, and
      mercuribenzoic acid) in anesthetized bile duct-cannulated rats injected with
      sodium [(75)Se]selenite (10 micromol/kg i.v.). The mercurial organic acids (10
      micromol/kg i.v.) differed strikingly from MM in their influence on selenium
      disposition. They promoted renal and hepatic accumulation as well as biliary
      excretion of selenium but decreased distribution to the muscle, testis, and brain
      as well as the pulmonary excretion of selenium. In contrast, MM altered selenium
      distribution in an opposite fashion: it diminished the biliary output of selenium
      and enhanced selenium exhalation. GC-MS analysis verified that this latter
      paradoxical effect resulted from increased exhalation of dimethyl selenide.
      Further studies indicated that the MM-induced increase in pulmonary excretion of
      dimethyl selenide cannot be due to a diminished conversion of this volatile
      selenium compound to trimethylselenonium ion (TMSe(+)), because MM influenced
      neither the urinary excretion nor the hepatic and renal concentration of TMSe(+)
      in selenite-injected rats. Compared to the selenite-exposed rats, the selenite
      plus MM-injected animals exhibited a significant rise in the hepatic level of S
      adenosylmethionine (SAME), the endogenous methyl donor in selenium methylation,
      and the ratio of SAME to S-adenosylhomocysteine. Based on these and others'
      observations, it is hypothesized that MM may increase hepatic availability of
      SAME in selenite-dosed rats by counteracting selenite-induced inactivation of
      SAME synthetase, thereby facilitating SAME synthesis, and/or by acting as a
      methyl donor in formation of dimethyl selenide, thereby sparing SAME. In summary,
      the toxicologically and ecologically relevant interaction of MM and selenite is
      not mimicked by organic acid mercurials, possibly because it results in formation
      of lipophilic Hg- and Se-containing common compound(s) and because it also
      appears to involve methyl transfer from MM to selenium.

PMID- 11446834
TI  - Spatial reversal learning in Aroclor 1254-exposed rats: sex-specific deficits in
      associative ability and inhibitory control.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that
      have been associated with cognitive deficits in children exposed in utero.
      Cognitive deficits due to PCB exposure have also been documented in animal
      models, but the underlying behavioral mechanisms responsible for those deficits
      remain to be elucidated. The current study examined the effects of gestational
      and lactational exposure to PCBs on spatial discrimination-reversal learning
      (spatial RL) in rats using standard two-lever operant testing chambers. Pregnant
      Long-Evans rats (10/dose) received either 0 or 6 mg/kg Aroclor 1254 (A1254) po in
      corn oil from gestational day 6 to postnatal day 21. One male and one female from
      each litter were tested on spatial RL beginning at 190-220 days of age. Animals
      were reinforced with a 45-mg food pellet for pressing the lever associated with
      the correct spatial location (either left or right). After reaching 85% correct
      performance for 2 consecutive days, the opposite spatial location was reinforced.
      Five of these position reversals were given. Male rats exposed to A1254 made
      significantly more total errors (121.6 +/- 12.5) on the first reversal than
      controls (90.7 +/- 5.8). In contrast, female rats exposed to A1254 exhibited
      deficits on the fourth and fifth reversals (23.6 +/- 4.2, 17.0 +/- 2.8 and 36.7
      +/- 4.7, 26.8 +/- 2.5 for control and exposed animals, respectively). Response
      pattern analyses in the A1254-exposed male and female rats revealed fundamental
      differences in the underlying behavioral mechanisms responsible for the deficits.
      A1254-exposed males exhibited an increased tendency to incorrectly respond to the
      previously correct stimulus (i.e., perseverate) following a reversal while A1254
      exposed females exhibited impairments in their ability to make new associations
      with a reinforced spatial location (i.e., associative deficit). These data
      provide new insights into the underlying behavioral mechanisms that may be
      responsible for the spatial learning deficits observed in PCB-exposed rodents and
      monkeys.

PMID- 11446835
TI  - The choice of timing for diuresis renography: the F + 0 method.
AB  - OBJECTIVE: To investigate a method of diuresis renography where the
      radiopharmaceutical and frusemide (diuretic) are given simultaneously, in
      contrast to conventional renography which involves an intravenous injection with
      frusemide 20 min after administering the radiopharmaceutical (F + 20) or 15 min
      before (F - 15), with particular interest in the effect of this change on
      assessing split renal function and interpreting upper tract drainage dynamics.
      PATIENTS AND METHODS: In a prospective study, 29 patients (18 women and 11 men,
      mean age 47 years, range 21--86) were assessed. Each patient had two renograms
      taken over a 48-h period, either by the F + 20 or F - 15, and the F + 0 method:
      Data for split renal function and drainage curves were obtained in the usual way.
      Two independent assessments of the drainage curves were obtained and the results
      compared. RESULTS: The split function assessments were identical (< 5% variation)
      in all but two patients; 26 of 29 (90%) gave identical conclusions about the
      drainage curves. The three patients with discrepancies between the studies had
      either hugely dilated upper tracts or otherwise had multiple complicating
      factors, e.g. impaired renal function, neuropathic bladder. CONCLUSIONS: F + 0
      renography has been used in paediatric urological practice before, but there are
      no comparative studies and no data on its use in adults. This prospective study
      confirmed that in investigating dilated upper tracts, the F + 0 technique gives
      similar results to the conventional techniques. The F + 0 method has the
      potential to reduce the time required to undertake standard F + 20 renography but
      it may not be useful in evaluating the grossly dilated upper tract, where the F
      15 technique has the best record in terms of reducing equivocal results.

PMID- 11446836
TI  - Undiagnosed macroscopic haematuria revisited: a follow-up of 146 patients.
AB  - OBJECTIVE: To further investigate a group of patients with macroscopic haematuria
      who had no abnormalities on upper tract imaging and cystoscopy, to determine the
      appropriate follow up. PATIENTS AND METHODS: The hospital notes of patients who
      presented with frank haematuria between 1990 and 1998 and had no abnormality on
      cystoscopy and/or upper tract imaging were reviewed, with particular note made of
      any further bleeding or any other further urological problems. Those with < 2
      years of follow-up in the hospital notes were investigated by telephone or via
      their general practitioner to ensure that all patients had at least 2 years of
      follow-up after the initial investigation. RESULTS: Of the 146 patients in the
      study, 98 were alive and had no more bleeding after the initial investigation.
      None of them were found to have renal or urothelial tumours during the follow-up.
      Thirty-three patients had recurrent episodes of bleeding after the initial
      investigation; 26 of these had repeat investigations and one was found to have a
      renal pelvic transitional cell carcinoma on repeat intravenous urography. One
      patient in this subgroup had died from a subarachnoid haemorrhage; 15 other
      patients had died, 13 of non-urological causes and two of unknown causes.
      CONCLUSIONS: Of 146 patients with undiagnosed macroscopic haematuria, only one
      had a missed tumour and this was detected on further investigation for recurrent
      bleeding. These results confirm that repeat cystoscopy and upper tract imaging is
      only warranted in patients who have recurrent bleeding after initial
      investigation.

PMID- 11446837
TI  - Computerized contrast angiosonography: a new diagnostic tool for the urologist?
AB  - OBJECTIVES: To evaluate the diagnostic potential of echo-enhanced ultrasonography
      (US) for depicting the vascularization pattern of renal cell carcinoma (RCC), and
      calculating the first-pass effect using harmonic imaging, against that obtained
      by triphasic helical computed tomography (CT). PATIENTS AND METHODS: Sixty
      patients with surgically confirmed RCC underwent US using B-mode and power
      Doppler methods with or without an intravenous microbubble echo-enhancing agent.
      After depicting and defining the tumour extent by B-mode US, the first-pass
      effect/enhancement by the echo-enhancing agent within the lesion, and that of a
      reference area of unaffected renal cortex, were recorded on-line by calculating
      the mean pixel intensity. Time-intensity curves, i.e. the rise time and gradient
      of both the suspected tumour and reference areas, were constructed. RESULTS:
      Using B-mode US, the extent of all tumours was delineated (mean tumour size 3.8
      cm, SD 0.6). After applying the microbubble agent all tumours were enhanced,
      whereas the perfusion was decreased (in 48%), increased (in 16%) or similar (in
      36%) compared with the cortical reference area. Using the Hounsfield
      classification, these results correlated well with the hypo/hypervascularity
      shown on CT. CONCLUSION: Ultrasonography has considerable potential in diagnosing
      RCC, if combined with echo-enhancing methods, harmonic imaging and computer-based
      calculation of tumour vascularization. Dynamic US studies should provide a
      diagnostic yield similar to that of CT.

PMID- 11446838
TI  - Selective urological evaluation in men with febrile urinary tract infection.
AB  - OBJECTIVE: To investigate the prevalence and clinical importance of urological
      abnormalities in men with community-acquired febrile urinary tract infection
      (UTI). PATIENTS AND METHODS: In this prospective study, 85 men (median age 63
      years, range 18--86) were followed for 1 year after an episode of febrile UTI.
      They were investigated by excretory urography, cysto-urethroscopy, uroflowmetry,
      digital rectal examination and measurement of postvoid residual urine volume by
      abdominal ultrasonography. RESULTS: The radiological examination of the upper
      urinary tract in 83 patients revealed 22 abnormal findings in 19 men. Relevant
      clinical abnormalities leading to surgical intervention were found in only one
      patient who had renal calyceal stones. The lower urinary tract investigation
      disclosed 46 findings in 35 men. In all, surgically correctable disorders were
      found in 20 patients, of whom 15 had previously unrecognized abnormalities. All
      patients who required surgery were identified either by a history of voiding
      difficulties, acute urinary retention at the time of infection, the presence of
      microscopic haematuria at follow-up after one month, or early recurrent
      symptomatic UTI. CONCLUSION: Routine imaging studies of the upper urinary tract
      seem dispensable in men with febrile UTI. To reveal abnormalities of clinical
      importance, any urological evaluation should primarily be focused on the lower
      urinary tract.

PMID- 11446839
TI  - Reliability and validity of the International Prostate Symptom Score in a
      Malaysian population.
AB  - OBJECTIVE: To validate the English version of the International Prostate Symptom
      Score (IPSS) in patients with and without urinary symptoms in a Malaysian
      population. PATIENTS AND METHODS: Validity and reliability were assessed in
      patients with lower urinary tract symptoms (LUTS) and in patients with no LUTS.
      Reliability was evaluated using the test-retest method and internal consistency
      using Cronbach's alpha. Sensitivity to change was expressed as the effect size in
      the score before and after intervention in additional patients with LUTS who
      underwent transurethral resection of the prostate (TURP). RESULTS: Internal
      consistency was excellent; there was a high degree of internal consistency for
      each of the seven domains and for the total score (Cronbach's alpha > or = 0.60
      and > or = 0.79, respectively) in the populations studied. The test-retest
      correlation coefficient for the seven domain scores was highly significant. The
      intra-class correlation coefficient was high (> or = 0.59). There was a high
      level of sensitivity and specificity for the effects of treatment, with a very
      significant change between the seven scores domains in the treated group but not
      in the control group. CONCLUSIONS: The IPSS is suitable, reliable, valid and
      sensitive to clinical change in the Malaysian population.

PMID- 11446840
TI  - The optimal form of urinary drainage after acute retention of urine.
AB  - OBJECTIVE: To assess the outcome of different forms of urinary drainage,
      particularly for urinary tract infection (UTI), operative findings and patient
      preference, in patients treated for acute urinary retention (AUR). PATIENTS AND
      METHODS: A feasibility trial was conducted of men presenting with AUR; after a
      short period of indwelling catheterization (IDC) patients were taught how to use
      clean intermittent self-catheterization (CISC). Patients who failed this were re
      catheterized and taught to manage a valve, or failing this a leg bag, and then
      discharged home. The patients were followed to assess the occurrence of
      spontaneous voiding, UTI, findings at prostatectomy and patient satisfaction.
      RESULTS: The CISC group (34 men) had a higher rate of spontaneous voiding than
      the IDC group (16 men; 56% vs 25%). The incidence of UTI was 32% in the CISC and
      75% in the IDC group. At TURP, 20% in the CISC group had a UTI, compared with 69%
      in the IDC group. Patients using CISC preferred it and had fewer complications
      than the IDC group. The CISC group had a similar ability to manage and similar
      acceptance of their method of drainage as the IDC group. CONCLUSION: CISC is
      managed and accepted well by patients who can use the technique and results in
      fewer UTIs. It should be considered in patients who present with AUR, and it may
      delay surgery.

PMID- 11446841
TI  - A double-blind, randomized, placebo-controlled pilot study to investigate the
      effects of finasteride combined with a biodegradable self-reinforced poly L
      lactic acid spiral stent in patients with urinary retention caused by bladder
      outlet obstruction from benign prostatic hyperplasia.
AB  - OBJECTIVE: To assess whether patients in acute urinary retention from benign
      prostatic enlargement can be treated with a combined therapy comprising
      finasteride and a bioabsorbable self-reinforced poly L-lactic acid (SR-PLLA)
      urethral stent. PATIENTS AND METHODS: Fifty-five patients in acute urinary
      retention were treated as outpatients; they had a suprapubic catheter inserted
      and the SR-PLLA stent placed cystoscopically. After 2 weeks the patients were
      randomized to receive either finasteride 5 mg daily or placebo. They were
      assessed at baseline and at 6, 12 and 18 months for maximum urinary flow rate,
      prostate volume and serum prostate-specific antigen (PSA). RESULTS: Nineteen
      patients completed the study while 36 discontinued. There was a statistically
      significant increase in the mean maximum flow rate, and a statistically
      significant decrease in the prostatic volume and serum PSA in the finasteride
      group. The same number of patients discontinued in both groups; the major reason
      for discontinuation was insufficient therapeutic response. CONCLUSIONS: The major
      problems were discontinuation of treatment because the response to therapy was
      insufficient, and uncontrolled breakdown of the spiral stent. To solve these
      problems, new configurations of bioabsorbable stents are needed.

PMID- 11446842
TI  - Fears, sexual disturbances and personality features in men with prostatitis: a
      population-based cross-sectional study in Finland.
AB  - OBJECTIVE: To determine the occurrence of mental distress related to prostatitis
      in Finnish men. SUBJECTS AND METHODS: A population-based cross-sectional survey
      was conducted of 2500 men aged 20--59 years living in the two northernmost
      provinces of Finland (Oulu and Lapland). The final response rate was 75% (1832
      men). RESULTS: The fear of undetected prostate cancer was reported by 17% of the
      men in the population who had had prostatitis, a value significantly higher (P <
      0.001) than in healthy men. Fears of having a sexually transmitted disease and
      suicidal thinking were also slightly more common. The men who had had prostatitis
      preferred to be alone in a public toilet during voiding (58% vs 44%, P < 0.001).
      Erectile dysfunction was reported by 43% of the men with symptomatic prostatitis
      and decreased libido by 24%. Self-assessment of personality, adjusted for age,
      showed that the men with prostatitis were more often busy and nervous than the
      healthy controls (P < 0.001), and that they had a more meticulous attitude to
      life and its problems. Marital difficulties were reported by 17% of the men who
      had had prostatitis at some point in their lives, and 4% were convinced that
      their illness had caused their divorce. Socio-economic status and social well
      being had no apparent influence on the occurrence of prostatitis. CONCLUSIONS:
      This survey showed that psychological stress is common in men with prostatitis.
      Urologists and general practitioners should consider that a consultation with a
      psychiatrist may be appropriate for selected men with prostatitis.

PMID- 11446843
TI  - Dorsal or ventral placement of the preputial/penile skin onlay flap for anterior
      urethral strictures:does it make a difference?
AB  - OBJECTIVE: To report our experience in managing complex anterior urethral
      strictures with a dorsally/dorsolaterally placed penile/preputial vascularized
      flap, and to discuss the advantages of this procedure over a traditional
      ventrally placed flap. PATIENTS AND METHODS: Between 1995 and 1999, 40 patients
      (mean age 40.5 years) with recurrent strictures of the pendulous and/or bulbar
      urethra were treated with longitudinal penile/circumpenile flap substitution
      urethroplasty. Nineteen patients underwent dorsal placement of the flap as an
      onlay (DO), whereas 21 patients had a ventral onlay (VO). Five patients needed
      inferior pubectomy to facilitate high proximal placement of the flap. RESULTS:
      Both groups had statistically similar ages, number of previous interventions,
      stricture site, length and follow-up. After a median follow-up of 27.5 months,
      the stricture recurred in three (24%) of the VO and two (11%) of the DO groups (P
      > 0.05). One patient in the VO group required surgical closure of the urethral
      fistula. Flap pseudo-diverticulum and/or sacculation with postvoid dribble
      occurred in six patients in the VO and none in the DO group (P = 0.01).
      CONCLUSIONS: Dorsal placement of the pedicled flap is anatomically and
      functionally more appropriate than the traditional VO placement. DO
      preputial/penile flap urethroplasty is a versatile procedure and can be applied
      even for long anterior urethral strictures, including reconstruction of the
      meatus and high proximal bulbar strictures.

PMID- 11446844
TI  - Prevalence of urinary incontinence in women with cystic fibrosis.
AB  - OBJECTIVE: To determine the prevalence of urinary incontinence (UI) in female
      patients (aged > or = 15 years) attending a cystic fibrosis (CF) centre, in whom
      stress UI could be common, as chronic coughing and sputum production are frequent
      symptoms associated with progressive lung disease in these patients. PATIENTS AND
      METHODS: An anonymous questionnaire was completed by 176 women with CF (mean age
      24.6 years, SD 5.8) during routine assessments as outpatients. RESULTS: In all,
      72 patients (41%) were classified as never incontinent; occasional UI was
      reported in 61 women (35%). Regular UI, occurring twice or more a month for at
      least two consecutive months in the last year, was reported in 43 patients (24%).
      Regular UI was associated with increasing age and a lower mean (SD) forced
      expiratory volume/s (of that predicted) than in women with no urinary symptoms,
      at 26.9 (6.5) years and 53.5 (23.5)%, and 23.1 (5.4) years and 65.5 (23.2)%,
      respectively (P < 0.01 and P < 0.05, respectively). All incontinent women
      recorded stress UI; coughing, laughing and physical activity were associated with
      UI in 92%, 33% and 21% of the patients, respectively. CONCLUSION: Stress UI is a
      common symptom in women with CF. As urine loss can be under-reported to the
      healthcare providers, women should be asked about incontinence as part of their
      routine follow-up. Pelvic floor muscle exercises are effective in treating stress
      UI and should be considered for those with CF and regular UI.

PMID- 11446845
TI  - Vaginal retropubic urethropexy with intraoperative cystometry for treating
      urinary stress incontinence.
AB  - OBJECTIVE: To determine the effectiveness of a vaginal retropubic urethropexy
      with intraoperative cystometry in treating urinary stress incontinence. PATIENTS
      AND METHODS: One hundred patients with genuine stress incontinence on urodynamic
      examination underwent the procedure and were followed up for 1 year; 96 completed
      the follow-up (four were lost to follow-up). RESULTS: At 1 year, 91 patients
      (95%) were cured of their stress incontinence and five (5%) failed, with
      recurrent stress incontinence developing. The complications were mainly of suture
      erosion (6%). CONCLUSION: This method of urethropexy has produced excellent
      results to date, with low complication and morbidity rates, and continues to be
      our treatment of choice. A randomized control trial comparing it with standard
      established procedures would be welcomed.

PMID- 11446846
TI  - Value of the serum prostate-specific antigen-alpha 1-antichymotrypsin complex and
      its density as a predictor for the extent of prostate cancer.
AB  - OBJECTIVE: To determine whether serum levels of the prostate-specific antigen
      alpha1-antichymotrypsin complex (PSA-ACT) and its density (ACTD) in patients
      scheduled to undergo radical prostatectomy for clinically localized prostate
      cancer can predict organ-confined vs extraprostatic disease. PATIENTS AND
      METHODS: Serum samples were obtained from 62 patients with clinically localized
      prostate cancer before they underwent radical prostatectomy. PSA and PSA-ACT were
      measured using immunofluorometric techniques with different monoclonal antibodies
      against PSA and ACT, respectively. Furthermore, the PSA and PSA-ACT densities of
      the whole prostate (PSAD and ACTD, respectively) were calculated. The
      relationships of serum PSA, PSA-ACT, PSAD, ACTD and the pathological stage of the
      prostatectomy specimens were analysed. RESULTS: The disease was organ-confined or
      extraprostatic in 30 and 32 men, respectively. In men with organ-confined cancer,
      the mean PSA and PSA-ACT levels were significantly lower than in those with
      extraprostatic disease. Furthermore, there were significantly higher mean PSAD
      and ACTD levels in men with extraprostatic than with organ-confined disease.
      There were also significant differences in PSA, PSA-ACT, PSAD and ACTD levels at
      each pathological stage, whereas there was no significant association between
      these variables and the Gleason score. Receiver-operating characteristic curve
      analysis for detecting organ-confined disease showed that PSA-ACT and ACTD had a
      larger area under the curve than PSA and PSAD, respectively, but these
      differences were not significant. Furthermore, PSA-ACT and ACTD provided
      significantly better sensitivity for detecting organ-confined disease than PSA
      and PSAD, respectively. CONCLUSIONS: Measuring PSA-ACT and ACTD may improve the
      preoperative evaluation of patients scheduled to undergo radical prostatectomy,
      because these factors better differentiate extraprostatic from organ-confined
      disease than PSA and PSAD.

PMID- 11446847
TI  - Comparative evaluation of treatments for erectile dysfunction in patients with
      prostate cancer after radical retropubic prostatectomy.
AB  - OBJECTIVE: To assess the effectiveness of a progressive local treatment protocol
      for erectile dysfunction (ED) in patients after undergoing radical retropubic
      prostatectomy (RRP) for prostate cancer. PATIENTS AND METHODS: The study included
      85 patients (mean age 59.5 years, range 50--75) with ED after RRP. Treatment was
      offered in four progressive phases, with patients passing to the next phase only
      if they failed the previous one: in phase I patients used a vacuum erection
      device; in phase II, sildenafil; in phase III, intracorporal injection; and in
      phase IV, intracorporal injection plus the vacuum erection device. The patients
      were followed for 1 year. RESULTS: Of the 85 patients, 78 (92%) responded to the
      vacuum erection device (with an erection sufficient for vaginal penetration), but
      only 11 (14%) agreed to continue with it at home. Of the remaining 74 patients,
      69 with no contraindications were given sildenafil and 14 (20%) had a positive
      response. Sixty patients were then treated with intracorporal injection and 51
      (85%) had a positive response; four of the nine failures in phase III responded
      to intracorporal injection plus vacuum therapy. Five patients failed all four
      protocols. After 1 year of follow-up, 76 of the 80 patients were successfully
      continuing treatment at home; seven (9%) used the vacuum erection device, 11
      (14%) sildenafil, 54 (71%) intracorporal injection and four (5%) intracorporal
      injection plus the vacuum erection device. CONCLUSION: Overall, this progressive
      treatment method gave a positive response in 80 of the 85 patients (94%). After 1
      year of follow-up, 76 of the 80 patients (95%) continued to respond well. Of all
      the methods used, intracorporal injection was the most effective for ED after
      RRP.

PMID- 11446848
TI  - Acetyl-L-carnitine vs tamoxifen in the oral therapy of Peyronie's disease: a
      preliminary report.
AB  - OBJECTIVE: To detect whether oral acetyl-L-carnitine might be useful in the acute
      and early chronic phases of Peyronie's disease, compared with tamoxifen, a drug
      currently in use. PATIENTS AND METHODS: The study included 48 patients with
      Peyronie's disease (15 acute and 33 initial chronic), randomized equally into two
      groups. The first group used tamoxifen 20 mg twice daily for 3 months and the
      second acetyl-L-carnitine 1 g twice daily for 3 months. The disease and stages
      were diagnosed and identified using a history, objective examination,
      pharmacologically induced erection, autophotography during erection, and basic
      and dynamic colour Doppler ultrasonography. Penile curvature, plaque size, pain
      and disease progression were assessed. The differences between the groups or
      between the variables before and after therapy were compared using analysis of
      variance or the chi-squared test. RESULTS: Acetyl-L-carnitine was significantly
      more effective than tamoxifen in reducing pain and in inhibiting disease
      progression. Acetyl-L-carnitine reduced penile curvature significantly, while
      tamoxifen did not; both drugs significantly reduced plaque size. Tamoxifen
      induced significantly more side-effects than acetyl-L-carnitine. CONCLUSIONS:
      These results suggest that acetyl-L-carnitine is significantly more effective and
      safe than tamoxifen in the therapy of acute and early chronic Peyronie's disease.

PMID- 11446849
TI  - Prevalence of undiagnosed diabetes mellitus in male erectile dysfunction.
AB  - OBJECTIVE: To determine the prevalence of previously undiagnosed diabetes
      mellitus (DM) in men presenting with erectile dysfunction (ED), using fasting
      blood glucose (FBG) compared with urinary dipstick testing for glycosuria.
      PATIENTS AND METHODS: A prospective prevalence study was carried out in an
      andrology outpatient clinic of a urology department in a district general
      hospital serving a mixed urban and rural population. In all, 129 consecutive men
      presenting with ED underwent FBG and urinary dipstick testing to detect
      undiagnosed DM in those presenting with ED. RESULTS: The prevalence of known DM
      was 17% and the that of undiagnosed DM 4.7% of the 107 remaining men; an abnormal
      fasting glucose level was found in a further 12%. The sensitivity of urine
      dipstick test for diagnosing DM was 20%. CONCLUSIONS: The prevalence of
      undiagnosed DM is higher in men with ED than in the general population. ED is a
      marker symptom for DM and DM should be actively sought in men presenting with ED.
      Urinary dipstick testing for glycosuria, if used as a screening test, will miss
      the diagnosis in 80% of these men. FBG testing should be undertaken to reliably
      diagnose DM in men presenting with ED.

PMID- 11446850
TI  - Brucellar epididymo-orchitis in Saudi Arabia: a retrospective study of 26 cases
      and review of the literature.
AB  - OBJECTIVE: To review the clinical and laboratory features and response to
      treatment of patients with acute brucellar epididymo-orchitis reporting to a
      tertiary care hospital in Riyadh, and to compare these with other cases reported
      previously. PATIENTS AND METHODS: In this retrospective study, records of all 26
      adult patients with brucellosis, who presented with epididymitis or epididymo
      orchitis at a tertiary hospital in Riyadh from 1983 to 2000, were reviewed.
      Positive blood culture or high agglutination titres of > or = 1 : 320 and
      positive clinical manifestations of brucellosis were the main criteria for
      diagnosing brucellosis. Among these cases, epididymitis or epididymo-orchitis was
      diagnosed on the basis of a typical history of gradual onset of scrotal pain and
      findings of enlarged tender testes and/or epididymis. RESULTS: Epididymo-orchitis
      occurred in 1.6% of all patients with brucellosis. Most (58%) were 25--44 years
      old; approximately 77% of the patients presented with acute symptoms of < 2
      weeks' duration. All patients complained of swollen painful testicles. Other
      presenting symptoms included undulant fever (96%), chills (54%) and arthralgia
      (23%). Four patients had dysuria and one haematuria. Ten patients gave a positive
      history of ingestion of raw milk and milk products; one patient had laboratory
      acquired brucellosis. Six patients had unilateral epididymo-orchitis (two with
      features of florid presentation); the remaining 20 had only orchitis (bilateral
      in two, right in 10 and left in eight). Leucocytosis was present in six patients;
      25 had initial agglutination titres of > 1 : 320 and the remaining patient had a
      positive blood culture. All patients received combined therapy with streptomycin
      for the first 2 weeks (or oral rifampicin for 6 weeks) with doxycycline or
      tetracycline for 6 weeks. All showed improvement, fever subsided in 2--5 days and
      the scrotal enlargement and tenderness regressed. Only one patient had a relapse
      within one year. CONCLUSION: In brucellosis-endemic areas, clinicians
      encountering epididymo-orchitis should consider the likelihood of brucellosis. A
      careful history, a meticulous physical examination and a rapid laboratory
      evaluation help in diagnosis. Clinical and serological data are sufficient for
      diagnosis. Leucocytosis is not an atypical feature of brucellar epididymo
      orchitis and so cannot be used for differentiating it from the nonspecific
      variety. Conservative management with combination antibiotic therapy is adequate
      for managing brucellar epididymo-orchitis.

PMID- 11446851
TI  - Upper pole heminephrectomy: is complete ureterectomy necessary?
AB  - OBJECTIVE: To determine the re-operation rate on the distal ureter after upper
      pole heminephrectomy with incomplete ureterectomy. PATIENTS AND METHODS: The case
      notes from one institution were reviewed retrospectively; 60 upper pole
      heminephrectomies with incomplete ureterectomy were undertaken in 39 girls and 16
      boys (mean age at primary surgery 27 months, range 3--88). RESULTS: Thirty-two
      children (58%) had an antenatal diagnosis while 12 (22%) presented with a urinary
      tract infection (UTI) and six (11%) with urinary incontinence. Twenty-nine of the
      60 renal units (48%) had an associated ureterocele and in nine (15%) the ureter
      was ectopic. Ten infants (18%) underwent initial puncture of a ureterocele. Five
      patients (8%), all females, required lower urinary tract re-operation. The
      indications for secondary surgery were recurrent UTIs in all and a prolapsed
      ureterocele in one. All five had ultrasonographic evidence of a dilated ureteric
      stump. Reflux into the retained stump was detected in one child. CONCLUSIONS: The
      re-operation rate for a redundant ureteric stump in this series was 8%. The risk
      of injury to the good ureter may outweigh the benefits of a complete
      ureterectomy.

PMID- 11446852
TI  - The role of the adult urologist in the care of children: findings of a UK survey.
AB  - OBJECTIVE: To document the current role of adult urologists in the care of
      children in the UK and to consider the future provision of urological services
      for children within the context of published national guidelines. METHODS: A
      detailed postal questionnaire was sent to all 416 consultant urologists listed as
      full members of the British Association of Urological Surgeons and resident in
      the UK. The range of information sought from each urologist included details of
      personal paediatric training, scope of personal practice, and information about
      facilities and provision of urological services for children in their base
      National Health Service hospital. RESULTS: The response rate was 69%; most
      consultant urologists (87%) in District General Hospitals (DGHs) undertake
      paediatric urology, mainly routine procedures of minor or intermediate
      complexity. Of urologists in teaching hospitals, 32% treat children but their
      involvement is largely collaborative. Consultants appointed within the last 10
      years are less willing to undertake procedures such as ureteric reimplantation or
      pyeloplasty than those in post for > or = 10 years. Currently, 18% of DGH
      urologists hold dedicated children's outpatient clinics and 34% have dedicated
      paediatric day-case operating lists. Almost all urologists practise in National
      Health Service hospitals which meet existing national guidelines on the provision
      of inpatient surgical care for children. CONCLUSION: Urologists practising in
      DGHs will retain an important role as providers of routine urological services
      for children. However, the tendency for recently appointed consultants to limit
      their practice to the more routine aspects of children's urology is likely to
      increase. Training and intercollegiate assessment should focus on the practical
      management of the conditions most commonly encountered in DGH practice. The
      implementation of national guidelines may require greater paediatric
      subspecialization at DGH level to ensure that urologists treating children have a
      paediatric workload of sufficient volume to maintain a high degree of surgical
      competence.

PMID- 11446853
TI  - Histopathological examination of both ipsilateral and contralateral testes with
      different obstructive models in prepubertal and adult rats.
AB  - OBJECTIVE: To determine the histopathological changes in both the ipsilateral and
      contralateral testes of prepubertal and adult male rats 60 days after creating
      different obstructive models. MATERIAL AND METHODS: Thirty-six prepubertal and 32
      adult albino male rats were examined in three different obstructive models of the
      right testis. In group 1 the spermatic cord was ligated, in group 2 the ligation
      was between the caput epididymis and testis, and in group 3 the vas deferens was
      ligated. Sixty days after ligation both testes were removed and evaluated for
      testis diameter, mean seminiferous tubule diameter (MSTD), and degenerative,
      obstructive and inflammatory changes. RESULTS: The diameter of the obstructed
      right testis and MSTD were significantly greater in prepubertal rats but there
      was no apparent difference in adult rats. For obstructive changes, sloughing of
      germ cells in the prepubertal rats and germ cell absence in adult rats were
      significantly more common in group 3. The contralateral testis diameter and MSTD
      of group 3 was significantly greater only in prepubertal rats. Statistically
      significant values of obstructive change, e.g. sloughing of germ cells and apical
      vacuolation in Sertoli cells, were apparent in prepubertal rats, but tubular
      ectasis was the only statistically significant criterion of obstruction in adult
      rats. CONCLUSION: The testes are more susceptible to obstruction of the vas
      deferens in prepubertal than in adults rats, resulting in increased hydrostatic
      pressure and oedema of both the ipsilateral and contralateral testes, which might
      be caused by collateral circulation and rat testicular microcirculation, with a
      rhythmic pattern of arteriolar dilatation and constriction (vasomotion). Although
      the presence of oedema and high hydrostatic pressure was not prominent in adults,
      formation of spermatic granulomas and absence or sloughing of germ cells in the
      obstructed and contralateral testes reflect the early effects of vas ligation on
      spermatogenesis in adulthood.

PMID- 11446854
TI  - The effect of methylene blue on histological damage after spermatic cord torsion
      in a rat model.
AB  - OBJECTIVE: To investigate, in a rat model, whether methylene blue (a free-radical
      scavenger) is effective in alleviating the histological testicular damage caused
      by reperfusion after spermatic cord torsion. MATERIALS AND METHODS: Male Wistar
      rats underwent a clockwise 720 degrees left spermatic cord torsion lasting 3 h;
      they were then randomly assigned to treatment and control groups. In the treated
      group, 2 mg/kg methylene blue was injected intraperitoneally 20 min before the
      cord was untwisted, and an additional 1 mg/kg injected into the penile vein 1--2
      min beforehand. After 14 days, the left testicle was removed and assessed
      histologically. The control group was not treated. RESULTS: Thirty-three rats in
      the treatment group and 35 untreated controls were suitable for evaluation.
      Treatment with methylene blue was not significantly predictive of histological
      damage; the colour of the testis before detorsion was not correlated with
      histological damage. CONCLUSION: Anti-oxidant treatment with methylene blue had
      no palliative effect on the histological changes after torsion and detorsion of
      the spermatic cord in this rat model.

PMID- 11446855
TI  - The protective effects of captopril and nitric oxide on solitary kidney after
      chronic partial ureteric obstruction.
AB  - OBJECTIVE: To determine whether vasodilator agents (captopril and nitric oxide)
      change the morphological and functional effects of chronic partial ureteric
      obstruction in solitary kidney tissue in unilaterally nephrectomized rats.
      MATERIALS AND METHODS: Each of 50 prepubertal Wistar albino rats underwent right
      nephrectomy and were then assigned to one of five groups. Rats in group 1
      underwent a sham operation (control) and in the other groups the ureter of the
      remaining kidney was partially obstructed by surgery. In group 2, no drug
      treatments were given; in groups 3, 4 and 5 captopril, L-arginine methyl ester (L
      Arg) or NG- nitro-L-arginine-methyl ester, respectively, were given for 3 weeks.
      In all rats, diuretic scintigraphy was used to measure kidney perfusion,
      glomerular filtration rate (GFR) and concentration. Blood urea nitrogen (BUN),
      serum creatinine levels, kidney parenchymal weight and pelvic volume were
      measured and the kidneys evaluated histopathologically. RESULTS: Renal perfusion
      was significantly greater in both group 3 and 4 than in group 2. The GFR was 18%
      greater in group 3 and 22.3% greater in group 4 than in group 2. The GFR was
      decreased by 67% in group 5 compared with the control group. The mean parenchymal
      weight, mean pelvic volume, BUN and serum creatinine in the four groups with a
      partially obstructed ureter were significantly different from the control group.
      There also were significant differences between group 2 and groups 3--5, and
      between group 2 and group 3. Histological damage was severe in all four groups
      with partial ureteric obstruction, but in the drug-treated groups, medullary
      fibrosis was less frequent. CONCLUSION: After 3 weeks of treatment, captopril and
      L-Arg both improved kidney perfusion, GFR, BUN and serum creatinine levels, but
      were less effective in preventing parenchymal atrophy and changes in pelvic
      volume.

PMID- 11446856
TI  - Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low-
      and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma.
AB  - OBJECTIVE: To elucidate the incidence of inducible nitric oxide synthase (iNOS)
      expression in benign prostatic hyperplasia (BPH), low- and high-grade prostatic
      intraepithelial neoplasia (PIN) and prostatic carcinoma lesions, and to explore
      the role of iNOS in prostate tumorigenesis. MATERIALS AND METHODS:
      Immunoreactivity for iNOS was examined in 20 samples each of BPH, high-grade PIN,
      low-grade PIN and prostatic carcinoma. RESULTS: Positive iNOS immunostaining was
      detected in all samples from all patients; iNOS was detected in both basal
      epithelial cells and secretory cells of the glandular epithelium. High-grade PIN
      and prostatic carcinoma samples had more intense iNOS immunostaining than low
      grade PIN and BPH samples. In all samples, smooth muscle cells showed weak or
      moderate iNOS immunoreactivity and endothelial cells showed moderate
      immunostaining. CONCLUSIONS: Nitric oxide generated by iNOS may be involved in
      prostate tumorigenesis and further studies with immunohistochemical and molecular
      biology are needed to determine the exact role of iNOS in the pathogenesis of
      prostatic carcinoma.

PMID- 11446857
TI  - Gracilis muscle flap with a tissue-engineered lining for experimental bladder
      wall reconstruction.
AB  - OBJECTIVE: To assess a pedicled gracilis muscle flap pre-laminated with
      autologous, in vitro-expanded urothelial cells to reconstruct an entire
      supratrigonal bladder-wall defect in rats. MATERIALS AND METHODS: A gracilis
      muscle flap was harvested from 36 male Wistar rats, transposed into the abdomen
      and wrapped around a silicon-block space holder. Urothelial cells were harvested
      and expanded ex vivo. Cells were then suspended in fibrin glue and seeded into
      the gracilis muscle pocket. One week later this pre-laminated flap was transposed
      into a surgically created supratrigonal bladder-wall defect. All animals
      underwent such a pre-laminated gracilis flap bladder reconstruction and were
      categorized into three experimental groups. All surviving animals with urothelial
      culture pre-laminated gracilis flap bladder reconstruction were killed 12 weeks
      (group 1) later. Control rats had gracilis flaps with no cell seeding and treated
      only with fibrin glue (group 2) or a standard culture medium (group 3) before
      reconstruction. RESULTS: Specimens stained with haematoxylin and eosin, and a
      specific immunohistochemical staining (AE1 and AE3-anti-cytokeratin monoclonal
      antibody stain) showed a continuous, multilayered functioning urothelial lining
      along the transposed pre-laminated gracilis flap in group 1. All animals in group
      1 with an intact urothelial lining on the gracilis muscle survived, in contrast
      to most animals in groups 2 and 3, where eight and all 12 animals died,
      respectively. The surviving four animals in group 2 had no detectable urothelial
      lining. CONCLUSION Successful urinary reconstruction requires a contractile neo
      reservoir resistant to resorption over time and a stable, protective urothelial
      lining. A gracilis muscle flap can be seeded with autologous cultured urothelial
      cells suspended in fibrin glue. This pre-laminated flap can be safely transposed
      on its pedicle and be successfully integrated into the remaining bladder wall,
      with a urothelial lining and the potential to contract. Further studies in larger
      animals, with a urodynamic assessment, are warranted to determine if this type of
      bladder-wall replacement technique is suitable for urinary reconstruction in
      humans.

PMID- 11446858
TI  - Castration-induced reduction of vascular endothelial growth factor expression in
      benign human prostate tissue is lost in advanced prostate cancer.
AB  - OBJECTIVE: To determine the role of vascular response in the castration-induced
      regression of benign and malignant human prostate tissue, as recent studies show
      that castration rapidly decreases blood flow and induces endothelial cell death,
      which may be important for subsequent epithelial cell death and involution of the
      glandular tissue of the prostate. MATERIALS AND METHODS: The expression of
      vascular endothelial growth factor (VEGF) and its receptors was analysed using
      the quantitative reverse transcriptase-polymerase chain reaction, in benign and
      tumour areas of core biopsies taken before, and approximately 1 week after
      castration therapy. The castration-induced VEGF response was related to therapy
      induced changes in tumour cell apoptotic index and subsequent response in serum
      prostate-specific antigen (PSA). In another set of patients, serum VEGF was
      quantified by enzyme-linked immunosorbent assay before, and at 3--6 months after
      castration therapy. RESULTS: VEGF mRNA was down-regulated after castration in
      benign prostate tissue (P < or = 0.05), whereas in tumour tissue, VEGF levels
      were reduced in some of the patients but unchanged or increased in others. In
      most patients whose tumour tissue responded with VEGF reduction, there was a
      corresponding increase in tumour cell apoptosis. Serum VEGF levels were not
      significantly changed after castration. Almost all patients responded with a
      substantial reduction in serum PSA after castration. CONCLUSION: Castration
      reduces VEGF mRNA expression in benign prostate tissue and generally in those
      prostate tumours where castration also induces tumour cell apoptosis. This
      suggests that a therapy-induced down-regulation of VEGF could be important for
      tumour cell death.

PMID- 11446859
TI  - Photodynamic investigation of mucosa-associated human papillomavirus
      efflorescences.

PMID- 11446860
TI  - Renal infarction in an elderly woman with atrial fibrillation.

PMID- 11446861
TI  - Hyperammonaemic encephalopathy associated with retention of urine in multiple
      large diverticula.

PMID- 11446862
TI  - Population-based outcomes after 28,246 in-hospital vasectomies and 1902
      vasovasostomies in Western Australia.

PMID- 11446864
TI  - Comparison of complications after radical and partial nephrectomy: results from
      the National Veterans Administration Surgical Quality Improvement Program.

PMID- 11446865
TI  - The value of aspirin in controlling the symptoms of nocturnal polyuria.

PMID- 11446866
TI  - Ethanol-glycine irrigating fluid for transurethral resection of the prostate in
      practice.

PMID- 11446868
TI  - The management of intractable haematuria.

PMID- 11446871
TI  - The overactive bladder.

PMID- 11446872
TI  - Modern sperm retrieval techniques and their usefulness in oocyte fertilization.

PMID- 11446873
TI  - Prostatic intraepithelial neoplasia and putative precursor lesions of prostate
      cancer: a clinical perspective.

PMID- 11446874
TI  - Possibilities for preventing recurrent calcium stone formation: principles for
      the metabolic evaluation of patients with calcium stone disease.

PMID- 11446875
TI  - Toward prevention of hepatocellular carcinoma developing in chronic hepatitis C.

PMID- 11446876
TI  - Optimal surveillance of hepatocellular carcinoma in patients with chronic viral
      hepatitis.

PMID- 11446877
TI  - History of viral hepatitis: a tale of dogmas and misinterpretations.

PMID- 11446878
TI  - A randomized open trial for comparison of proton pump inhibitors, omeprazole
      versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation
      to CYP2C19 genetic polymorphism.
AB  - BACKGROUND AND AIM: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has
      been shown to influence the efficacy of Helicobacter pylori eradication therapy
      with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy).
      Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in
      different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we
      compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in
      relation to CYP2C19 polymorphism. METHODS: One hundred and ninety-nine patients
      with peptic ulcer disease were randomly assigned to receive one of the following
      regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole
      or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a
      bacterial culture and a [(13)C]-urea breath test at 1--2 months after completion
      of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase
      chain reaction-restriction fragment length polymorphism. RESULTS: Intention-to
      treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95%
      CI, 56--75) and 62.4% (95% CI, 52--71), respectively, without significant
      difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure
      rates in either of these regimens. We analyzed various factors associated with
      treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple
      logistic regression; smoking was the only significant independent factor for
      treatment failure. CONCLUSION: Omeprazole and rabeprazole were equally effective
      in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI
      used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking
      significantly decreased the cure rate of H. pylori infection in the dual therapy.

PMID- 11446879
TI  - Investigation of the extent of gastric metaplasia in the duodenal bulb by using
      methylene blue staining.
AB  - BACKGROUND AND AIMS: The existence of gastric metaplasia (GM) of the duodenal
      mucosa has been considered to be highly related to the recurrence of duodenal
      ulcers (DU). The aims of this study are to evaluate the usefulness of methylene
      blue staining in the detection of GM, and to clarify the relationship between GM
      and the deformity of the duodenal bulb. METHODS: Fifteen patients with healed DU
      and four patients with symptoms of dyspepsia without evidence of ulcers were
      enrolled into this endoscopic study. During each endoscopy, methylene blue was
      sprayed evenly on the duodenal bulb, and biopsies were taken from blue-stained
      and unstained areas. The existence and extent of GM were assessed histologically
      and grossly. The correlation between duodenal bulb deformity and the extent of GM
      was also studied. RESULTS: The mean score of methylene blue non-staining (MBNS)
      was 0, 1.30 +/- 0.15, and 3.00 +/- 0.00 in group A (non-ulcer patients), group B
      (patients with healed DU and with normal-shaped bulb) and C (patients with healed
      DU and with deformed duodenal bulb), respectively; showing significant
      differences among the groups (P < 0.05 in each). Both the existence and the
      grading of GM were higher in unstained specimens than in blue-stained specimens
      (100 vs 16.6%, P < 0.0001 and 3.62 +/- 0.09 vs 0.19 +/- 0.06, P < 0.001,
      respectively). CONCLUSIONS: Methylene blue non-staining can be applied to
      investigate the existence and extent of GM in the duodenal bulb accurately. The
      incidence of GM in the duodenal bulb was higher in patients with healed ulcers
      than in non-ulcer patients. Patients with deformed duodenal bulbs have a higher
      extent of GM than those without deformed duodenal bulbs.

PMID- 11446880
TI  - Clinicopathological features of gastric mucosa-associated lymphoid tissue
      lymphoma: a comparison with diffuse large B-cell lymphoma without a mucosa
      associated lymphoid tissue lymphoma component.
AB  - BACKGROUND AND AIMS: The aim of this study was to clinicopathologically
      distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT)
      lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component
      (DLL). METHODS: We investigated clinicopathological features of these gastric
      lymphomas including age, sex ratio, tumor location and depth, macroscopic
      appearance, and infection with Helicobacter pylori of these gastric lymphomas and
      hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10
      patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency
      of H. pylori infection in lymphoma patients was compared with that in age- and
      sex-matched control subjects. RESULTS: There was a predominance of females with
      MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9
      for high-grade MALT lymphomas), and there was a predominance of males with DLL
      (male to female ratio, 13/6); the ratios differed significantly (P < 0.05).
      Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT
      lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells
      invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori
      infection occurred significantly more often in patients with low-grade MALT
      lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely,
      the frequency of H. pylori infection in DLL patients did not differ from that in
      controls. CONCLUSIONS: These data suggest that H. pylori infection may be
      associated with the development of gastric MALT lymphoma, but not DLL, and that
      MALT lymphoma and DLL may have a different pathogenesis.

PMID- 11446881
TI  - Influence of gender difference and gastritis on gastric ulcer formation in rats.
AB  - BACKGROUND: Male patients with gastritis are found to have a high risk of
      developing peptic ulcer diseases. However, how gastritis or gender difference
      affects gastric ulcer formation is unclear. The present study aimed to
      investigate the relationship between ethanol-induced acute gastritis and gastric
      ulcer formation in rats. METHODS: Acute gastritis or gastric ulcer was induced in
      the rat stomach by 80% ethanol or 60% acetic acid, respectively. Rats were killed
      either with gastritis alone or thereafter at day 1, 3 or 6 after ulcer induction.
      The number of proliferating and apoptotic cells, the mucosal mucus and
      prostaglandin E(2) (PGE(2)) level were also determined. RESULTS: Male rats with
      acute gastritis potentiated gastric ulcer formation, while gastritis in female
      rats prevented ulceration. Female rats with gastritis had a significantly faster
      ulcer-healing rate. More apoptotic cells were found in the gastritis groups, but
      only the female gastritis group produced more proliferating cells and had a
      decrease in the apoptosis-over-proliferation ratio. The mucus level was higher in
      female rats after ulcer induction. Mucosal PGE(2) level was higher in female rats
      with acute gastritis. Both mucus and PGE(2) were increased during ulcer healing
      in both genders. CONCLUSIONS: This study shows that gender difference plays a
      role in the pathogenesis of ulcer formation. The number of cells with apoptosis
      or proliferation determines, in part, the gender difference on gastric ulcer
      formation in rats. Gastric PGE(2) not only contributes to this process, but also
      together with gastric mucus participates in the ulcer-healing process in the
      stomach.

PMID- 11446882
TI  - Medium-chain fatty acids stimulate interleukin-8 production in Caco-2 cells with
      different mechanisms from long-chain fatty acids.
AB  - BACKGROUND AND AIM: It has been suggested that dietary fat exacerbates intestinal
      inflammation. We investigated the effect of fatty acids on interleukin (IL)-8
      production in a human intestinal epithelial cell line (Caco-2). METHODS: The
      cells were cultured as monolayers on microporous membranes in culture inserts.
      Oleic acid (OA), capric acid (CA), docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA) were applied to the apical compartment of Caco-2 cell
      monolayers. The concentration of IL-8 in the basolateral medium was measured by
      using enzyme-linked immunosorbent assay, and the expression of IL-8 mRNA was
      measured by using competitive reverse transcription--polymerase chain reaction.
      Protein kinase C inhibitors (GF109203X and calphostin C) and H-7 (a protein
      kinase inhibitor) were used to study the mechanisms by which IL-8 production is
      stimulated. RESULTS: Both OA and CA enhanced IL-8 production (approximately
      fivefold), whereas DHA and EPA did not. Both OA and CA also enhanced IL-1-induced
      IL-8 production. The onset of OA-induced IL-8 production was delayed compared
      with that of CA-induced IL-8 production. Both OA and CA enhanced IL-8 mRNA
      expression (approximately fivefold) after 6 and 3 h, respectively. The protein
      kinase inhibitor (H-7) reduced both OA- and CA-induced IL-8 production by 88.0
      and 85.9%, respectively. The protein kinase C inhibitors (GF109203X and
      calphostin C) reduced OA-induced IL-8 production by 29.3 and 54.5%, respectively,
      but showed no effect on CA-induced IL-8 production. CONCLUSIONS: These findings
      suggest that not only OA but also CA stimulates IL-8 production in intestinal
      epithelial cells, and the mechanisms of action differ between OA and CA.

PMID- 11446883
TI  - Modulation of acid secretion in common bile duct ligation-related gastropathy in
      Wistar rats.
AB  - BACKGROUND: Portal hypertensive gastropathy is associated with fundic gland
      atrophy, resulting in a decrease in chief and parietal cells, and diminished acid
      secretion. METHODS: Acid secretion by isolated parietal cells was measured
      (acridine orange retention), along with the levels of various second messengers
      (intracellular Ca(2+), cyclic adenosine monophosphate and protein kinase C) in
      the common bile duct, ligated portal hypertensive rats and compared with sham
      operated controls. RESULTS: There was a significant decrease in the response of
      isolated parietal cells to the secretagogues histamine and carbachol. This
      resulted in the blunted acid secretion in the common bile duct ligated group. In
      addition, all the second messengers studied were significantly decreased as
      compared with the sham-operated controls. CONCLUSION: These results suggest that
      the blunted acid secretory response in the portal hypertensive rat is caused by
      an alteration in the intracellular signal transduction mechanism.

PMID- 11446884
TI  - Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor
      necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover
      proteins, and radiologic and endoscopic findings.
AB  - BACKGROUND: Several studies have reported that the chimeric monoclonal antibody
      to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the
      treatment of Crohn's disease. The aim of this study was to clarify the efficacy
      of this treatment in Japanese patients with Crohn's disease. METHODS: A 12-week
      multicenter, open trial of Infliximab was carried out and involved 25 patients
      with moderate to severe Crohn's disease who were resistant to conventional
      treatment. Patients received a single 2-h intravenous infusion of Infliximab at a
      dose of 1, 3, 5 or 10 mg/kg bodyweight. Clinical evaluation of this treatment
      response was defined as a reduction in the index of the inflammatory bowel
      disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in
      serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an
      increase in serum levels of rapid turnover proteins as well as improvement of
      radiologic and endoscopic findings at 4 weeks. RESULTS: The IOIBD score was
      reduced after 4 weeks in 66.7% of the group receiving 1 mg/kg Infliximab, 71.4%
      in the group receiving 3 mg/kg, 80.0% in the group receiving 5 mg/kg, and 85.7%
      in the group receiving 10 mg/kg. Improvement was better maintained over 12 weeks
      in the 5 and 10 mg/kg groups compared with the 1 and 3 mg/kg groups. Similar
      results were obtained for the CDAI scores. Serum levels of rapid turnover
      proteins significantly increased to within the normal ranges after infusion in
      all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of
      radiologic and endoscopic findings. CONCLUSIONS: A single infusion of Infliximab
      was effective for the treatment of Japanese patients with Crohn's disease. Serum
      rapid turnover proteins reflected the clinical response to antibody for TNF-alpha
      well.

PMID- 11446885
TI  - Laterally spreading tumor: clinicopathological study in comparison with the
      depressed type of colorectal tumor.
AB  - AIM: To evaluate the difference between laterally spreading colorectal tumors
      (LSTs) with depression and depressed-type colorectal tumors. METHODS: Sixteen
      LSTs showing the appearance of non-distinct, gently sloping central depressions
      were compared clinicopathologically with 14 depressed-type tumors that were
      larger than 10 mm in size. RESULTS: The mean size of LSTs with depression was
      13.5 +/- 3.4 mm, which was significantly larger than that of the depressed type
      colorectal tumors (11.2 +/- 1.5 mm). The invasion of the depressed-type
      colorectal tumors was significantly deeper than that of LSTs with depression,
      despite the larger size of the LSTs. The surface structures (pit patterns) of
      both types of tumors were apparently different; the pit patterns of LSTs with
      depression were almost of the type IIIL pit, while that of the depressed-type
      tumors were almost of type V pits (P < 0.01). Histologically, LSTs with
      depression appeared to grow in a superficial replacing manner on the edge of the
      lesions, while depressed-type tumors grew in an expanding manner. CONCLUSION: It
      seems appropriate that these LSTs with depression should be distinguished from
      depressed-type colorectal tumors and regarded as constituting a new clinical
      entity.

PMID- 11446886
TI  - Diagnostic value of serum type IV collagen test in comparison with platelet count
      for predicting the fibrotic stage in patients with chronic hepatitis C.
AB  - BACKGROUND AND AIM: The serum type IV collagen test is now used as a diagnostic
      aid for the detection of liver fibrosis and cirrhosis. Recently, a platelet count
      has been reported to be a useful marker for assessing the fibrotic stage in
      chronic hepatitis C. The aim of this study was to compare the usefulness of the
      serum type IV collagen test and platelet count for diagnosing the fibrotic stage
      in chronic hepatitis C patients. METHODS: The diagnostic values were assessed by
      the use of receiver operating characteristic (ROC) analysis in 165 patients with
      chronic hepatitis C, with the exception of those patients with cirrhosis.
      RESULTS: The serum type IV collagen level increased, and the platelet count
      decreased significantly with the progression of fibrosis staging. As judged from
      ROC curves, the serum type IV collagen test was more useful than the platelet
      count for differentiating moderate or severe fibrosis from no or mild fibrosis.
      At a cut-off value of 110 ng/mL, the serum type IV collagen test had an overall
      diagnostic accuracy of 75%, while at a cut-off value of 16 x 10(4)/mm(3), the
      platelet count had a diagnostic accuracy of 70%. The serum type IV collagen test
      and platelet count were similar in differentiating severe fibrosis from no, mild
      or moderate fibrosis. Both serum type IV collagen (at a cut-off value of 130
      ng/mL) and platelet count (at a cut-off value of 14 x 10(4)/mm(3)) had a
      diagnostic accuracy of 73%. CONCLUSION: The serum type IV collagen test was
      slightly superior to the platelet count for assessing the fibrotic stage in
      patients with chronic hepatitis C.

PMID- 11446887
TI  - Effect of interferon therapy on Japanese chronic hepatitis C virus patients with
      anti-liver/kidney microsome autoantibody type 1.
AB  - AIM: The aim of this study was to determine the prevalence of anti-liver/kidney
      microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected
      Japanese patients at various stages (chronic hepatitis, liver cirrhosis and
      hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on
      interferon therapy. METHODS: A total of 390 serum samples from 215 HCV-infected
      patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver
      cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to
      examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served
      as controls. Anti-liver/kidney microsome autoantibody type 1 was determined by
      using a newly developed ELISA using recombinant cytochrome P450 IID6 as the
      antigen. RESULTS: Anti-liver/kidney microsome autoantibody type 1 was detected in
      six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two
      were HCV-LC); in contrast, it was not detected in control groups. Among the 110
      HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1.
      No change in anti-LKM-1 immunoreactivity from negative to positive during
      interferon therapy was observed. Moreover, no increase in the serum alanine
      aminotransferase level was observed in these four patients with anti-LKM-1.
      CONCLUSION: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver
      disease associated with HCV infection; and (ii) no change in anti-LKM-1
      immunoreactivity from negative to positive or no aggravations of liver
      dysfunction were observed among HCV-CH patients during the IFN therapy for
      Japanese patients with liver disease.

PMID- 11446888
TI  - 'Pseudo-aldosteronism' induced by intravenous glycyrrhizin treatment of chronic
      hepatitis C patients.
AB  - BACKGROUND AND AIMS: Treatment with intravenous glycyrrhizin reduces the
      progression of liver disease caused by chronic hepatitis C (HCV) infection.
      Glycyrrhetinic acid, a metabolite of glycyrrhizin, inhibits the renal conversion
      of cortisol to cortisone by inhibiting the enzyme 11 beta
      hydroxysteroiddehydrogenase in the kidney. The resulting excess of cortisol
      subsequently stimulates the mineralocorticoid receptor, leading to pseudo
      aldosteronism with hypertension, hypokalemia and eventually renin and aldosterone
      suppression. The aim of this study was to evaluate the occurrence of pseudo
      aldosteronism after treatment of chronic hepatitis C (HCV) patients with
      increasing doses of intravenous glycyrrhizin. METHODS: Forty-four HCV patients
      with chronic hepatitis or compensated cirrhosis were treated with intravenous
      glycyrrhizin 6 x 200 mg/week, 3 x 240 mg/week or 3 x 0 mg/week (placebo) for 4
      weeks. In all patients, bodyweight, blood pressure and plasma concentrations of
      sodium, potassium, cortisol, DHEA-S (dehydroepiandrosterone sulfate), renin and
      aldosterone were measured before, and at 0 and 4 weeks after treatment. RESULTS:
      Within the placebo group, no significant changes were observed. Within the 1200
      mg group systolic blood pressure was significantly higher at the end of
      treatment, while aldosterone was significantly lower; at the end of the follow-up
      period these values had returned to baseline. The changes from baseline in
      systolic and diastolic blood pressure at the end of treatment were significantly
      higher in the 1200 mg group compared to the placebo group. The changes in
      aldosterone and potassium concentrations at the end of treatment increased with
      increasing dosage, although not significantly. CONCLUSION: Hepatitis C virus
      patients with chronic hepatitis or compensated cirrhosis show minor reversible
      symptoms of pseudo-aldosteronism after treatment with 1200 mg glycyrrhizin weekly
      for 4 weeks.

PMID- 11446889
TI  - Systemic and splanchnic hemodynamics following hemorrhage and volume restitution
      with Haemaccel in portal hypertensive rats: the effect of propranolol.
AB  - BACKGROUND AND AIMS: Recently, we found in a portal hypertensive rat model that
      hemorrhage and volume restitution with Haemaccel, a low viscosity plasma
      expander, induced an increase in cardiac output and portal venous inflow. The
      present study was conducted to evaluate whether pretreatment with propranolol
      will attenuate these hyperdynamic changes. METHODS: Portal hypertension was
      induced by portal vein constriction. Treatment was initiated 14--21 days later.
      Propranolol (30 mg/kg per day) or water were administered for 7 days via a
      gastric gavage. Under ketamine anesthesia, 18 h after the last given dose, blood
      was withdrawn at a constant rate of 0.3 mL/min for 15 min followed by a 15-min
      stabilization. Haemaccel was infused at the same rate and volume used for
      withdrawal. Hemodynamic measurements were performed after volume restitution in
      both groups by using radioactive microspheres. RESULTS: Eight rats were studied
      in each group. In the propranolol-treated animals, portal venous inflow was
      decreased (2.4 +/- 0.8 vs 3.8 +/- 0.7 mL/min per 100 g bodyweight; P < 0.01),
      while splanchnic arteriolar and porto-collateral resistance were increased (52.8
      +/- 21.0 vs 32.8 +/- 13.0 and 6.0 +/- 1.4 vs 4.1 +/- 0.7 mmHg x min x 100 g
      bodyweight/mL; P < 0.05, respectively). Cardiac output, mean arterial pressure,
      heart rate, total peripheral resistance and portal pressure were not
      significantly different between the two groups. CONCLUSION: In this model,
      pretreatment with propranolol prevented the increase in portal venous inflow,
      which occurs following hemorrhage and volume restitution with Haemaccel. Although
      caution should be taken in extrapolating data from animal models to humans, our
      results suggest that volume replacement during a portal hypertensive-related
      bleeding episode may be safer in a patient treated with non-selective beta
      adrenoreceptor antagonists.

PMID- 11446890
TI  - Intraductal ultrasonography for hepatocellular carcinoma with tumor thrombi in
      the bile duct: comparison with polypoid cholangiocarcinoma.
AB  - BACKGROUND AND AIM: Tumor thrombi in the bile duct caused by hepatocellular
      carcinoma (HCC), and cholangiocarcinoma show polypoid lesions on cholangiographic
      findings. This study prospectively compared the images of intraductal
      ultrasonography between HCC and polypoid cholangiocarcinoma. METHODS: In five
      patients with tumor thrombi in the bile duct caused by HCC, a 2.0 mm diameter
      ultrasonic probe with a frequency of 20 MHz was inserted into the bile duct via
      the transpapillary route (n = 4) or the transhepatic route (n = 1). The images
      were compared to that of 65 patients with cholangiocarcinoma. RESULTS: In all
      patients with HCC, intraductal ultrasonography showed a 'polypoid tumor with a
      narrow base'. In 16 of 65 patients with cholangiocarcinoma, it showed a 'polypoid
      tumor with a narrow base'. When intraductal ultrasonography showed a 'polypoid
      tumor with a narrow base', the findings of a positive 'nodule within a nodule'
      (40 vs 0%; P < 0.05), and the absence of a 'papillary-surface pattern' (80 vs
      13%; P < 0.05) were more highly associated with tumor thrombi caused by HCC than
      to polypoid-type cholangiocarcinoma. CONCLUSIONS: Intraductal ultrasonography was
      useful to distinguish between tumor thrombi caused by HCC and polypoid-type
      cholangiocarcinoma.

PMID- 11446891
TI  - Maintenance of connexin 32 and 26 expression in primary cultured rat hepatocytes
      treated with 3-acetylpyridine.
AB  - BACKGROUND AND AIM: We recently reported that primary rat hepatocytes treated
      with 3-acetylpyridine (3-AP), an analog of nicotinic acid, could maintain hepatic
      differentiated functions such as albumin, tryptophan 2,3-dioxygenase, and
      connexin 32 (Cx32) mRNA expressions for more than a week. In the present
      experiment, we investigated the expression of not only Cx32, but also Cx26 in
      cells treated with 10 mmol/L 3-AP in detail. METHODS: We examined the expression
      of Cx32 and Cx26 in primary rat hepatocytes by using the methods of
      immunocytochemistry, immunoelectron microscopy, northern blotting, and dye
      transfer. RESULTS: The hepatocytes treated with 3-AP were polygonal with a large
      cytoplasm from day 3, and were maintained for approximately 2 weeks, whereas the
      cells without 3-AP began to die from day 4. Immunocytochemically in the cells
      with 3-AP, many Cx32- and Cx26-positive spots were observed between most adjacent
      cells, and the intensity of positive spots increased with time in culture,
      whereas in the cells without 3-AP, Cx32- and Cx26-positive spots disappeared at
      day 4. Furthermore, most Cx26-positive spots were colocalized with Cx32-positive
      ones. The amounts of Cx32 and Cx26 mRNA transcripts in the cells with 3-AP at day
      14 were more than 80% and approximately 30% of those of Cx32 and Cx26 mRNA
      transcripts in the cells at day 1, respectively. Gap junctional intercellular
      communication was maintained in the cells treated with 3-AP at day 8, although it
      was lost in the cells without 3-AP. CONCLUSION: Thus, the addition of 10 mmol/L 3
      AP to the medium enhanced the maintenance of Cx32 and Cx26 expression, which is
      one of the hepatic differentiated functions, in primary rat hepatocytes for a
      long time.

PMID- 11446892
TI  - Cisapride improves gallbladder emptying and bile lipid composition in patients
      with gallstones.
AB  - BACKGROUND AND AIM: Biliary cholesterol supersaturation, gallbladder stasis and
      delayed intestinal transit are the key events in cholesterol gallstone formation.
      We studied the effect of cisapride, a prokinetic drug, on gallbladder emptying
      and bile composition in patients with gallstone disease undergoing
      cholecystectomy. METHODS: Gallbladder emptying, cholesterol saturation index
      (CSI) and nucleation time were studied in 21 patients with gallstone disease.
      Eleven patients (cisapride group, age 41.9 +/- 2.9 years) received tablet
      cisapride 10 mg t.i.d. for 2 weeks, while 10 patients (placebo group, age 42.1 +/
      1.9 years) received placebo for the same duration. Gallbladder emptying was
      repeated in all patients after a 2-week treatment with cisapride or placebo.
      Gallbladder bile was obtained at the time of surgery for the measurement of CSI
      and nucleation time. RESULTS: Residual volume of the gallbladder decreased (mean
      +/- SE, 18.6 +/- 2.5 mL vs 10.0 +/- 1.1 mL, P = 0.007), and the ejection fraction
      increased (43.5 +/- 5.3% vs 60.0 +/- 3.2%, P = 0.007) in patients in the
      cisapride group, while no change was observed in placebo group patients.
      Nucleation time was higher in the cisapride group than in the placebo group (14.9
      +/- 1.3 days vs 8.0 +/- 0.9 days, P = 0.003). Patients in the cisapride group had
      a significantly lower cholesterol concentration (molar percentage, 5.1 +/- 0.3%
      vs 6.8 +/- 0.8%, P = 0.049) and CSI (1.0 +/- 0.1 vs 1.36 +/- 0.11, P = 0.034)
      than patients in the placebo group. CONCLUSION: Cisapride improves gallbladder
      emptying and bile lithogenicity in patients with gallstone disease.

PMID- 11446893
TI  - Hepatobiliary and pancreatic: intrahepatic portal vein anomaly. Duplicated portal
      vein.

PMID- 11446894
TI  - Gastrointestinal: intrathoracic upside-down stomach.

PMID- 11446896
TI  - A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and
      splenic metastasis.
AB  - Pseudomyxoma peritonei (PMP) is a rare clinical entity in which a diffuse
      collection of intraperitoneal gelatinous fluid is associated with gelatinous
      implants on the peritoneal surfaces and omentum. Hematogenic or lymphatic
      metastasis is extremely rare. In addition, an inguinal mass as an initial
      presentation is also relatively rare. This is a case report of a PMP patient who
      had splenic metastasis and showed an inguinal tumor as an initial presentation. A
      59-year-old female patient, who had undergone bilateral oophorectomy because of a
      ruptured ovarian mucinous tumor of boderline malignancy 12 years previously,
      presented a presumptive diagnosis of a left inguinal irreducible hernia. Computed
      tomography revealed a low density mass in the pelvic cavity and in the inguinal
      lesion, as well as in the spleen without any diseases around the organ. The
      preoperative serum carcinoembryonic antigen (CEA) level was elevated. The patient
      underwent a resection of gelatinous tumor in the pelvic cavity, splenectomy, and
      appendectomy, as well as left inguinal herniorrhaphy. Histological examinations
      revealed a splenic metastasis of PMP originating from the ovarian low-grade
      mucinous tumor. She received postoperative intraperitoneal lavage as well as
      chemotherapy, and has survived for over 7 years postoperatively without any
      evidence of recurrence, as confirmed by repeated follow-up CT examinations and
      CEA determination. Splenic metastasis of PMP is extremely rare; this represents
      only the third reported case of its kind in the literature. Furthermore, it
      should be noted that an inguinal tumor can sometimes be an initial presentation
      of PMP.

PMID- 11446897
TI  - A case of autoimmune hepatitis with a high titer of antimitochondrial antibody
      and normal gamma-globulinemia.
AB  - We report here a patient with chronic active hepatitis who had no markers for
      hepatitis viruses and no hyper-gamma-globulinemia, but had high titers of
      antimitochondrial antibody. Serum levels of alkaline phosphatase were normal, and
      antinuclear antibody, antismooth muscle antibody, and antiliver kidney microsome
      antibody tested negative. The titers of antimitochondrial antibody exceeded
      1:640, and the positivity for anti-M2 was ascertained by using both ELISA and
      immunoblot with beef-heart mitochondria and a recombinant pyruvate dehydrogenase
      E2 subunit as antigens. This patient responded to ursodeoxycholic acid (UDCA)
      therapy in the beginning, but her hepatitis flared up during UDCA therapy. In
      contrast, she responded completely to corticosteroid therapy. The clinical course
      and histological findings of this patient strongly suggest that this patient has
      autoimmune hepatitis.

PMID- 11446898
TI  - Macrocystic type of serous cystadenoma with a communication between the cyst and
      pancreatic duct.
AB  - A 42-year-old woman with a cystic lesion in the head of the pancreas was
      evaluated by using abdominal ultrasonography, a computed tomographic scan,
      magnetic resonance imaging and endoscopic retrograde pancreatography. Multiple
      cystic lesions, 5 cm in diameter, which had papillary protrusion inside the cyst
      in the head of the pancreas and had the communication between the cysts and
      pancreatic duct, were determined. Pylorus-preserving pancreaticoduodenectomy was
      performed under the diagnosis of mucinous cystic neoplasm of the pancreas.
      Although the cut surface of the tumor showed a macrocystic tumor of 3 cm in
      diameter, part of the cyst wall was cavernous. A histopathological examination
      showed single-layered cuboidal cells, which lead to the diagnosis as being serous
      cystadenoma of the pancreas. Serous cystadenoma is a rare, almost benign
      pancreatic tumor. The macrocystic subtype of serous cystadenoma is even more
      rare. We describe a patient who had this macrocystic subtype of serous
      cystadenoma with a communication between the cyst and pancreatic duct. This case
      illustrates the difficulty in the diagnosis of cystic lesions in the pancreas,
      and might support the single category of cystic lesions of the pancreas.

PMID- 11446899
TI  - Hepatitis B and C markers in a Kurdish refugee camp in Greece.

PMID- 11446900
TI  - Focal nodular hyperplasia treated by transcatheter arterial embolization using
      Lipiodol mixed with Gelfoam particles.

PMID- 11446901
TI  - Acute gastric mucosal lesions associated with cytomegalovirus infection in an
      immunocompetent adult.

PMID- 11446902
TI  - Alteration in expression of the rat mitochondrial ATPase 6 gene during
      Pneumocystis carinii infection.
AB  - BACKGROUND: Pneumocystis carinii causes pneumonia in immunocompromised patients
      with a high morbidity and mortality rate, but the interaction between this
      organism and the host cell is not well understood. The purpose of this research
      was to study the response of host cells to P. carinii infection on a molecular
      level. RESULTS: The technique of mRNA differential display was used to detect
      genes whose expression may be affected by P. carinii infection. The nucleotide
      sequence of one differentially displayed DNA fragment was found to be identical
      to that of the rat mitochondrial ATPase 6 gene, which is a subunit of the F0F1
      ATP synthase complex. A four-fold increase in expression of this gene was
      verified by Northern blot analysis of total RNA extracted from P. carinii
      infected rat lung versus that from mock-infected rat lung. Localization of the
      cells containing ATPase 6 mRNA was accomplished by in situ hybridization. In
      sections of non-infected rat lung, these cells were found lining the distal parts
      of the respiratory tree and in apical areas of the alveoli. Histological location
      of these cells suggested that they were Clara cells and type II pneumocytes. This
      hypothesis was confirmed by co-localizing the mRNAs for ATPase 6 and surfactant
      protein B (SP-B) to the same cells by two-color fluorescent in situ
      hybridization. CONCLUSIONS: The ATPase 6 gene is over expressed during P. carinii
      infection, and type II pneumocytes and Clara cells are the cell types responsible
      for this over-expression.

PMID- 11446903
TI  - Incidence and characteristics of total stroke in the United States.
AB  - BACKGROUND AND PURPOSE: Stroke, increasingly referred to as a "brain attack", is
      one of the leading causes of death and the leading cause of adult disability in
      the United States. It has recently been estimated that there were three quarters
      of a million strokes in the United States in 1995. The aim of this study was to
      replicate the 1995 estimate and examine if there was an increase from 1995 to
      1996 by using a large administrative claims database representative of all 1996
      US inpatient discharges. METHODS: We used the Nationwide Inpatient Sample of the
      Healthcare Cost and Utilization Project, release 5, which contains approximately
      20 percent of all 1996 US inpatient discharges. We identified stroke patients by
      using the International Classification of Diseases, 9th Revision, Clinical
      Modification (ICD-9-CM) codes from 430 to 438, and we compared the 1996 database
      with that of 1995. RESULTS: There were 712,000 occurrences of stroke with
      hospitalization (95% CI 688,000 to 737,000) and an estimated 71,000 occurrences
      of stroke without hospitalization. This totaled 783,000 occurrences of stroke in
      1996, compared to 750,000 in 1995. The overall rate for occurrence of total
      stroke (first-ever and recurrent) was 269 per 100,000 population (age- and sex
      adjusted to 1996 US population). CONCLUSIONS: We estimate that there were 783,000
      first-ever or recurrent strokes in the United States during 1996, compared to the
      figure of 750,000 in 1995. This study replicates and confirms the previous annual
      estimates of approximately three quarters of a million total strokes. This slight
      increase is likely due to the aging of the population and the population gain in
      the US from 1995 to 1996.

PMID- 11446904
TI  - Brief report on the effect of providing single versus assorted brand name condoms
      to hospital patients: a descriptive study.
AB  - OBJECTIVES: This study examined condom acquisition by persons in a hospital
      setting when single versus assorted brand name condoms were provided. METHODS:
      Condom receptacles were placed in exam rooms of two clinics. During Phase 1, a
      single brand name was provided; for Phase 2, assorted brand names were added.
      Number of condoms taken was recorded for each phase. RESULTS: For one clinic
      there was nearly a two-fold increase in number of condoms taken (Phase 1 to Phase
      2); for the second clinic there was negligible difference in number of condoms
      taken. CONCLUSIONS: The provision of assorted brand name condoms, over a single
      brand name, can serve to increase condom acquisition. Locations of condoms and
      target population characteristics are related factors.

PMID- 11446906
TI  - [Astrovirus infection in children with gastroenteritis].
AB  - OBJECTIVE: We report here a 2 year study (1997-1998) of astrovirus infection in
      children admitted to our hospital. The epidmioligical and clinical features of
      the infection were also investigated. METHOD: A total of 1.815 stool specimens
      were tested during a two-year period (january 1997- december 1998). They were
      collected from children less than 3 years of age admitted to La Paz Hospital
      (Madrid) with acute gastroenteritis. We used a monoclonal antibody-based enzyme
      inmunoassay (IDEIA Astrovirus, DAKO) to detect astrovirus antigen in faecal
      samples. RESULTS: Astroviruses were detected in 79 of the 1.815 analysed samples.
      This represented an incidence of 4,3%. The main symptom of infection was watery
      diarrhoea, and it was often associated with vomiting and fever. The majority of
      astrovirus infection occurred between the coldest months of the year. Children
      under a year of age were the most susceptible population. There was a
      considerable number of patients (62%) who develop the infection after 72 hours of
      admission. CONCLUSION: The rate of detection reported here illustrates the
      importance of this pathogen in childhood diarrhoea, so we recommend its screening
      on a routine basis.

PMID- 11446907
TI  - [Can the Brucellacapt test be substituted for the Coombs test in the diagnosis of
      human brucellosis?].
AB  - BACKGROUND: Throughout this work we have studied the capacity of Brucellacapt
      test to replace Coombs test in the serological diagnosis of human brucellosis.
      METHODS: A total of 66 initial sera from patients with diagnostic of brucellosis
      were studied. The patients were divided in two groups: 42 patients showing a
      primo-infection (group1), and 24 patients with a previous case of brucellosis
      (group 2). As a controls, for the group 1 we have used 100 sera from healthy
      donors, and for group 2, 28 sera from people that have had clinical brucellosis
      but actually are in good health. All serum samples were tested in either Coombs
      and Brucellacapt tests. The diagnostic yield was calculated using ROC (receiver
      operating characteristic) plots.Moreover, the results obtained in Coombs and
      Brucellacapt tests with 397 serum samples from 66 patients with brucellosis were
      compare with a non-parametric method. RESULTS: The sensibility and specificity
      for group1 were respectively 1 and 0.98 for Coombs and, 1 and 0.95 for
      Brucellacapt tests. For group 2, the results in Coombs test were 1 and 0.80, and
      in Brucellacapt test 0.95 and 0.74. In this second group, the area under the ROC
      plot was 0.950 for Coombs and 0.904 for Brucellacapt tests. Non statistical
      differences were observed comparing both serological tests using the Wilcoxon
      method (Z= -0.213; p=0.8). CONCLUSIONS: Brucellacapt and Coombs tests yield
      similar diagnostic results in the follow-up of serological samples from patients
      with brucellosis, and its should consider as interchangeables.

PMID- 11446908
TI  - [Escherichia coli eradication from the blader urine by amoxicillin-sulbactam.
      Intrinsic activity of the inhibitor].
AB  - RATIONALE: At urine concentrations obtained after the oral administration of
      amoxicillin-sulbactam (500/500 mg) this combination inhibits roughly 90% of
      Escherichia coli and Proteus mirabilis strains. AIMS: To administer amoxicilin
      sulbactam 875/125 mg and to determine: a) minimum inhibitory concentration (MIC)
      of sulbactam for E. coli and P. mirabilis; b) urine inhibitory titres power (UIT)
      against amoxicillin-resistant E. coli or P. mirabilis; c) urine concentrations of
      sulbactam; and to verify whether sulbactam 125 mg as single drug, attains a high
      enough UIT to support the intrinsic action of the inhibitor; and to compare the
      activity of amoxicillin-sulbactam and amoxicillin-clavulanate and that of
      sulbactam and clavulanate. METHODS: Twelve healthy volunteers received a single
      oral dose of amoxicillin-sulbactam 875/125 mg or amoxicillin-clavulanate 875/125
      mg, according to a randomized cross-over design. Urine samples were drawn at: 0
      (basal), 2, 4, and 6 hours after dosing. Urine pH, specific gravidity and UIP
      were assessed. Thirty nine strains isolated from urine samples were used: 30 TEM
      1 producing E. coli strains and 3 extended spectrum CTX-M-2 betalactamase
      producing E. coli; and 6 P. mirabilis resistant to both combinations. In 6
      healthy volunteers, sulbactam 125 mg was administered orally and UIT against E.
      coli (MIC amoxicillin > 2048 mg/l) was assessed. RESULTS AND DISCUSSION: MIC-90
      for amoxicillin plus sulbactam or clavulanate were similar to those for sulbactam
      or clavulanate alone, without any difference attributable to the chemical
      composition of the urine. The activity of amoxicillin plus the inhibitors could
      be due, not only to the inhibition of betalactamase but also to the intrinsic
      effect of the inhibitor. Both combinations showed an equivalent inhibitory
      activity. Two-hour UIT remained high for the entire 6-h evaluation period.
      Sulbactam concentration far exceed sulbactam MIC for the 6h-period, inhibiting
      urine E. coli. We disagree with the cut-off limit proposed for intermediate
      values of NCCLS, which, for these antimicrobial are 16/8, a value lower than
      those obtained in urine samples after the administration of betalactamase
      inhibitors. This may be an explanation for the beneficial effect of amoxicillin
      sulbactam in the recovery of uncomplicated lower urinary tract infections in
      women when the involved strains were considered resistant by diffusional methods.

PMID- 11446909
TI  - [Cefotaxime, twenty years later. Observational study in critically ill patients].
AB  - OBJECTIVE: Afer twenty years of commercial availability of cefotaxime, the
      objective of this study was to know the reasons and modes of use, administration
      dosage as well as its effectiveness and tolerance in critically ill patients
      admitted to Intensive Care Units (ICU) in our country. DESIGN: Open, prospective,
      observational, multicenter study. SUBJECTS: All patients who had cefotaxime
      administered in monotherapy or in combination with other antibiotics were
      included as cases in this study. RESULTS: A total of 624 patients were included
      in 44 ICUs (average 14 cases). Cefotaxime was indicated for therapy of 274
      community-acquired infections (43.9%), 194 prophylaxis (31.1%), and 156
      nosocomial infections (25.0%). Both community-acquired pneumonia (149, 34.7%) and
      mechanical ventilation associated pneumonia (62, 14.4%) predominated, followed by
      trachebronchitis (60, 13.9%) and central nervous system infections (42, 9.8%).
      Over half of infections (222, 51.6%) presented as systemic inflammatory response
      syndrome (SIRS), 133 (30.9%) as severe sepsis, and 75 (17.4%) as septic shock. In
      374 (87.0%) out of the 430 cases of infection treatment, cefotaxime wan
      prescribed on an empirical basis and in 150 of them (40.1%) a further
      confirmation of the causative agent was obtained. In 120 (27.9%) cases,
      cefotaxime was administered as monotherapy and in the remaining cases in
      association with one or more antibiotics.The use of cefotaxime as prophylaxis was
      evaluated as failure in 31 (16.0%) of the cases, whereas in treatment it was
      considered as failure in 98 (22.8%) of the 430 cases, 51 community-acquired
      infections, 27 (27.3%) of ICU-acquired infections, and 20 (35.1%) nosocomial
      infections acquired outside the ICU. In 127 (29.5%) of the 430 infection
      treatments the initial treatment was changed. The reasons for the change included
      clinical failure (36, 28.3%), recovery of an uncovered pathogen with the
      antibiotic (40, 31.5%), emergence of multi-resistant pathogens (28, 22.0%), to
      decrease the therapeutic spectrum (7, 5.5%), and other reasons (16). Cefotoxime
      was also changed in 21 (6.0%) of the 194 cases in which it was used as
      prophylaxis. In 32 (5.1%) patients 37 adverse effects were noted which were
      associated with a possible or likely use of cefotaxime. Most notably, diarrhoea
      in 15 (2.4%) occasions and skin rash in 6 cases (1.0%). CONCLUSIONS: Cefotaxime
      is still one of the therapies of choice for community-acquired and nosocomial
      infections as well as in different prophylactic modes. It is mostly used on an
      empirical basis and associated with other antibiotics. Clinical and
      microbiological efficiency is high whereas adverse effects related to its use
      have been scarce.

PMID- 11446910
TI  - [Populational pharmacokinetics: An approach to the].

PMID- 11446911
TI  - [Man with fever, pain and functional limitation of the right shoulder].

PMID- 11446912
TI  - [Enterovulvar and enteroanal fistula in a female patient infected with the human
      immunodeficiency virus].

PMID- 11446913
TI  - [Thirty-six year old male patient with dysphonia refractory to conventional
      medical treatment].

PMID- 11446914
TI  - [Cryptococcal meningits and pulmonary cryptococcoma in a patient with idiopathic
      CD4 lymphocytopenia].

PMID- 11446915
TI  - [Permethrin-resistant pediculosis].

PMID- 11446916
TI  - [Bacterial peritonitis due to Leclercia adecarboxylata in a patient undergoing
      peritoneal dialysis].

PMID- 11446917
TI  - [Empyema due to Salmonella enterica serotype enteritidis].

PMID- 11446918
TI  - [Salmonella sp. meningitis in the adult. Case report and review of the spanish
      literature].

PMID- 11446919
TI  - [Tricuspid endocarditis in a patient with ventriculo-atrial shunt].

PMID- 11446920
TI  - [Mastoidal infection due to Fusobacterium necrophorum in children. Report of two
      cases].

PMID- 11446921
TI  - [Diagnosis of retinitis of uncertain origin by means of nucleic acid
      amplification in the vitreous humor].

PMID- 11446922
TI  - [Borreliosis de Lyme en Espana].

PMID- 11446923
TI  - [Clinical study of 437 consecutive hepatectomies].
AB  - BACKGROUND: The aim of this prospective study was to analyze the risk of liver
      resection in unselected patients. PATIENTS AND METHOD: From 1990 to 2000, 437
      consecutive hepatectomies were performed in our center. Most frequent indications
      were liver metastases (n = 288), hepatocellular carcinoma (n = 62), Klatskin
      tumor (n = 17), gallblader carcinoma (n = 139) and other malignant tumors (n =
      6). The indication was a benign tumor in 51 patients. In 357 cases the liver
      parenchyma was normal, 51 patients had an underlying cirrhosis and 17 patients
      had an obstructive jaundice. RESULTS: Overall mortality was 3.6% (15 cases).
      Mortality in benign tumors was lacking. The prevalence of postoperative
      complications was 43.9%, which was mainly influenced by malignancy (46.9% vs
      21.6%, p = 0.001) and type of tumor (Klastkin tumor, p # 0.001). Major liver
      resection (p < 0.001), blood transfusion (p < 0.001), age over 60 years (p =
      0.001) and the type of hepatectomy (p < 0.001) also increased significantly the
      morbidity. The prevalence of biliary fistula was 11.2%, which was mainly related
      to the type of hepatectomy (major hepatectomy; p = 0.002) and a biliary-enteric
      anastomosis (p < 0.001). The prevalence of hepatic insufficiency was 3.6%, and
      chief risk factors for its development were underlying liver disease and major
      liver resection (p = 0.017). CONCLUSIONS: Mortality after hepatectomy in
      experienced centers is low. Morbidity is mainly related to the amount of
      parenchyma resected, type of hepatectomy, underlying liver disease and associated
      procedures. Liver resection should be performed preferentially in centers with
      high volume by specialized surgeons.

PMID- 11446924
TI  - [Effect of preconceptional metabolic control in the course of pregnancy in
      diabetic patients].
AB  - BACKGROUND: We analysed the relationship between metabolic control parameters
      during the preconception stage and pregnancy outcome in diabetic patients.
      PATIENTS AND METHOD: We examined 69 diabetic patients who underwent a
      preconception control at the Diabetes and Pregnancy Unit between 1992-1998. At
      the end of the preconception care period, 50 women (72.6%) became pregnant. Eight
      out of them (16%) had an abortion. RESULTS: Women who had an abortion did not
      differ from those who had not an abortion with regard to HbA1c levels at the end
      of the preconception period, age, duration of diabetes, age at diagnosis,anti
      thyroid antibodies or microvascular disease. Among 41 single age stations, fetal
      macrosomia was observed in 36.6% cases, neonatal hypoglycemia in 19.5% and major
      congenital malformations in one case. Average level of HbA1c was 7.6 +/- 1.3%and
      6.5 +/- 0.7 at the beginning and at the end of the preconception period,
      respectively (p < 0.001). In the group with macrosomia,average HbA1c at the end
      of the preconception period was 6.8 +/- 0.66% as opposed to 6.3 +/- 0.7% for the
      non-macrosomic group (p < 0.05). A linear correlation was seen between HbA1c
      levels at the end of the preconception period and infant weight (r = 0,432; p =
      0,014), birth weight ratio (r = 0,450; p = 0,009), and a morbidity score (r =
      0,458;p = 0,007). CONCLUSIONS: A better metabolic control during the
      preconception period may contribute to lessen the risk of fetal macrosomia and
      neonatal morbidity.

PMID- 11446925
TI  - [Analysis of psoriasis susceptibility regions in the Spanish population: evidence
      of a major gene involved in psoriasis in the 6p21 region].
AB  - BACKGROUND: Identification of the susceptibility regions to psoriasis in Spanish
      population. Analysis of the chromosomal regions 6p, 17q, 4q and 1cen-q21.
      PATIENTS AND METHOD: Analysis of 27 Spanish families with psoriasis. Parametric
      and non-parametric linkage analysis with 22 polymorphic microsatellite markers in
      the candidate regions. RESULTS: Evidence of linkage (p < 0,05) using non
      parametric methods in chromosome 6p. Absence of linkage in 17q, 4q and 1cen-q21
      regions. CONCLUSION: We present the evidence of a major gene in 6p21.3 involved
      in psoriasis in Spanish population.

PMID- 11446926
TI  - [Prion diseases. Pathogenic mechanisms].

PMID- 11446927
TI  - [Liquid ecstasy poisoning: study of 22 cases].
AB  - BACKGROUND: To describe characteristics of acute poisoning with liquid ecstasy
      (gammahydroxybutyrate, GHB). PATIENTS AND METHOD: Epidemiological and clinical
      data of patients with acute GHB poisoning seen at emergency department (ED) along
      one year were collected. RESULTS: 22 patients were included. Typical profile
      corresponds to a young male, who consults on weekend, at night, complaining of a
      marked decreased level of consciousness. Patients refer coingestion of other
      drugs and typically regain consciousness spontaneously in a short time.
      CONCLUSION: The frequency of GHB poisoning has increased notably in our
      environment. GHB poisoning must be considered on the differential diagnostic of
      coma of unknown origin in young patients attended in ED.

PMID- 11446928
TI  - [Drug-resistant tuberculosis in Spain. Trends and influence of the human
      immunodeficiency virus].

PMID- 11446929
TI  - [HELLP syndrome].

PMID- 11446930
TI  - [Prevention of colorectal cancer].

PMID- 11446931
TI  - [Autoimmune hepatitis following cytomegalovirus infection].

PMID- 11446932
TI  - [Severe hypercalcaemia as initial manifestation of B-cell non-Hodgkin's
      lymphoma].

PMID- 11446933
TI  - [Prolonged asystolia due to adenosine triphosphate].

PMID- 11446934
TI  - [Severe acute hepatitis caused by azathioprine].

PMID- 11446935
TI  - [Bilateral submandibular infection by the parotiditis virus].

PMID- 11446936
TI  - [Community acquired pneumonias followed in ambulatory care].

PMID- 11446939
TI  - [Thromboprophylaxis and neuroaxial anesthesia: watch carefully to prevent adverse
      effects].

PMID- 11446940
TI  - [Prophylactic antithrombotic therapy after orthopedic surgery with bemiparin, a
      second-generation low molecular weight heparin].
AB  - OBJECTIVE: Bemiparin is a new second generation low molecular weight heparin with
      a molecular weight of 3,600 daltons and an anti-Xa/anti-IIa ratio greater than 8.
      The aim of this study was to evaluate the efficacy and safety of bemiparin
      administered at a daily dose of 3,500 IU anti-Xa (40 mg), with prophylaxis
      beginning 6 hours after total hip replacement surgery. PATIENTS AND METHODS:
      Fifty-seven consecutive patients were evaluated by bilateral phlebography of the
      lower limbs 10 days after surgery. The patients were recruited at two centers
      specializing in orthopedic surgery. RESULTS: The incidence of deep venous
      thrombosis (DVT) in the series was 7% (95% CI: 0.4-13.7). In three patients (5%)
      DVT was proximal (95% CI 0-11.1). These results are consistent with those
      reported by Kakkar for bemiparin at the same dose begun two hours before surgery
      (incidence of DVT: 7.2%). No episodes of major bleeding were observed with this
      new protocol for postoperative administration. The incidence of wound hematoma
      was low and no patient required further surgery. The rate of post-operative
      bleeding was similar to that usually reported when low molecular weight heparin
      is used in hip surgery. CONCLUSIONS: Thromboprophylaxis in orthopaedic surgery
      with bemiparin beginning 6 hours after surgery appears to be safe and effective.

PMID- 11446941
TI  - [The effect of encephalogram bispectral index monitoring during total intravenous
      anesthesia with propofol in outpatient surgery].
AB  - OBJECTIVE: To assess the effect of monitoring the encephalogram bispectral index
      (BIS) during outpatient surgery. Outcome measures were amount of propofol
      administered, awakening and discharge. MATERIAL AND METHODS: Forty consecutive
      outpatient surgery patients were studied. The patients gave informed consent and
      received general intravenous anesthesia with propofol administered through a
      laryngeal mask using a computerized system (Diprifusor(R)). Two groups were
      formed: in group A, BIS was monitored, although the information was hidden from
      the anesthesiologists, who used the usual signs (loss of blinking reflex, pupil
      size and hemodynamic response) to guide anesthesia; in group B the
      anesthesiologists used BIS monitoring to guide propofol administration.
      Measurements were blood pressure, heart rate and BIS at six times during the
      procedure (T1-T6). Other data recorded were age, weight, height, propofol
      consumption in relation to weight and duration of procedure, consumption of
      rocuronium and alfentanil, duration of propofol infusion, time from withdrawal of
      propofol until eye opening, duration of stay in the post-anesthesia intensive
      care unit and time until total recovery. A questionnaire assessed the presence of
      intraoperative awareness and degree of satisfaction. The data were analyzed by
      Student's t and a chi square tests, with statistical significance at p < 0.05.
      RESULTS: Demographic variables (age, weight and height) were similar, as were
      duration of propofol infusion, total dose of alfentanil and rocuronium, evolution
      of blood pressure and heart rate. Statistically significant differences in BIS
      were observed at two times, T4 and T5; total propofol administered was 32.6%
      lower in group B; and time until eye opening was significantly shorter in group
      B. No significant differences were observed for time until full recovery. No
      instances of intraoperative awareness were reported and satisfaction was high in
      both groups. CONCLUSION: BIS monitoring allows for propofol titration that leads
      to a mean reduction of 32.6% in consumption, shortening the time until eye
      opening without causing intraoperative awareness or reducing patient
      satisfaction.

PMID- 11446942
TI  - [Drugs that alter hemostasis and regional anesthetic techniques: safety
      guidelines. Consensus conference].
AB  - Patients about to undergo surgery are often taking drugs that alter hemostasis
      and affect anesthesia, particularly when neuroaxial techniques are used for
      subarachnoid or epidural anesthesia. The aim of this paper is to provide safety
      guidelines for regional anesthesia in patients receiving hemostasis-altering
      drugs, in order to reduce the risk of bleeding. We offer a detailed discussion of
      patients treated with inhibitors of platelet aggregation (emphasizing that such
      treatment alone is not a contraindication for neuroaxial blockade although
      certainly guidelines must be followed), unfractionated heparin (anesthesia should
      be started at least 4 hours after administration of this drug or 30 minutes
      before, provided pulmonary arterial pressure is normal), low molecular weight
      heparin (which should be administered 12 hours before or 12 hours after the
      anesthetic technique), and oral anticoagulants (provision of regional anesthesia
      depends mainly on International Normalized Ratio monitoring). We also stress that
      removal of catheters should follow criteria similar to those listed above, that
      the risk of complications due to bleeding increases considerably in association
      with these drugs, and that adequate neurological monitoring is essential during
      postoperative recovery. Overall, the final decision to use regional anesthesia in
      patients receiving drugs that alter hemostasis must be made on an individual
      basis after assessment of benefit and risk.

PMID- 11446943
TI  - [Model to predict staffing for anesthesiology and post-anesthesia intensive care
      units and pain clinics].
AB  - Human resources account for a large part of the budgets of anesthesia and post
      anesthesia intensive care units and pain clinics (A-PICU-PC). Adequate staffing
      is a key factor in providing for both effective care and professional staff
      development. Changes in professional responsibilities have rendered obsolete the
      concept of one anesthesiologist per operating room. Duties must be analyzed
      objectively to facilitate understanding between hospital administrators and A
      PICU-PC chiefs of service when assigning human resources. The Catalan Society of
      Anesthesiology, Post-anesthesia Intensive Care and Pain Therapy has developed a
      model for estimating requirements for A-PICU-PC staffing based on three factors:
      1) Definition of staff positions that must be filled and criteria for assigning
      human resources; 2) Estimation of non-care-related time required by the
      department for training, teaching, research and internal management, and 3)
      Estimation of staff required to cover absences from work for vacations, personal
      leave or illness. The model revealed that the ratio of number of staff positions
      to number of persons employed by an A-PICU-PC is approximately 1.3. Differences
      in the nature of services managed by an A-PICU-PC or the type of hospital might
      change the ratio slightly. The model can be applied universally, independently of
      differences that might exist among departments. Widespread application would
      allow adoption of a common language to be used by health care managers and A-PICU
      PC departments when discussing a basis for consensus about our specialty.

PMID- 11446944
TI  - [Anesthetic management for cesarean delivery in a pregnant patient with
      congenital antithrombin III deficiency and pulmonary thromboembolism].
AB  - Antithrombin III (AT III) deficiency is a rare hereditary disease that
      predisposes a patient to thromboembolic complications. Anticoagulation is
      essential for preventing recurrence of thrombi. Concentrated AT III replacement
      is reserved for acute periods of thromboembolism or moments of increased risk.
      Hemostatic anomalies are generally considered a contraindication for regional
      anesthesia, due to the potential risk of spinal hematoma. This paper describes a
      woman with congenital AT III deficiency and heparin-treated pulmonary embolism
      whose pregnancy of 29 weeks had to be terminated by cesarean section upon signs
      of fetal distress. We discuss the pathophysiology and treatment in such cases.

PMID- 11446945
TI  - [Splenectomy in a patient with beta thalassemia intermedia and severe hemolytic
      anemia].
AB  - A 36-year-old woman with beta thalassemia intermedia suffered a hemolytic crisis
      secondary to Epstein-Barr virus infection. She was given a transfusion of
      phenotypically compatible blood. However, severe hemolysis persisted (with
      hemoglobin levels around 4 g/dl) in spite of gamma globulin and corticosteroid
      administration. Emergency therapeutic splenectomy was performed. We discuss
      intraoperative management in situations of severe anemia, concluding that it is
      possible to survive significant decreases in hemoglobin concentration with
      cardiocirculatory reserve and respiration intact, maintaining normal volume.

PMID- 11446946
TI  - [Anesthesia with EMLA cream: a promising application for plastic surgery].

PMID- 11446947
TI  - [Nurse-midwife competence in providing regional analgesia during labor].

PMID- 11446948
TI  - [Remifentanil for palliative abdominal surgery in a patient with myasthenia
      gravis].

PMID- 11446949
TI  - [Diagnosis by transesophageal echocardiography of an accidental cannulation of
      the left atrium by an inferior vena cava catheter].

PMID- 11446950
TI  - [Anesthetic management of hyperthyroidism and thyrotoxic crisis].

PMID- 11446951
TI  - [Apneic oxygenation: an innocouos technique?].

PMID- 11446954
TI  - [Who should treat heart failure?].

PMID- 11446955
TI  - [Ischemic heart disease in the elderly. Special Conference of the 36th National
      Congress of the Spanish Society of Cardiology].
AB  - In the field of Cardiology, older patients are the most frequently seen in
      clinical practice. In the USA, 60% of the patients hospitalized with acute
      myocardial infarction are 65 or older, as are almost 80% of the patients with
      heart failure. Population in industrialized countries is aging progressively and
      this fact is particularly pronounced in Spain, where, as calculated, the
      population pyramid will be inverted in the next 50 years and people over 65 will
      be a majority group. We know that age is a determinant factor in the prognosis of
      illness. With age, comorbidity increases, sex distribution changes, mortal
      complications have a higher incidence, and there are structural and mechanical
      functional changes. The specific characteristics of this group of patients and
      their enormous impact in clinical practice have led us to reconsider the medical
      focus used to approach this very important aspect of public health. Many of the
      larger randomized clinical trials have included a narrow spectrum of older
      patients despite the great relevance that the study of this group might have. On
      the other hand, the extrapolation of the results obtained in younger patients to
      older patients implies that the average results of the study may be assigned to a
      heterogeneous population, not taking into consideration the specificities of each
      subgroup. Therefore, there is a need to create innovative strategies to optimize
      the results in the older patient group. Even though clinical trials are a very
      useful tool to establish the effectiveness of a therapy, from a methodological
      point of view, they should include a higher number of older patients, and the
      observational studies undertaken with a rigorous methodology should be more
      frequently used to generate new knowledge and put the established knowledge info
      practice. Furthermore, observational studies can be particularly important in the
      development of strategies that allow the translation of information from the
      clinical trials to daily clinical practice.

PMID- 11446956
TI  - [Out-of-hospital cardiac arrest, our pending subject].

PMID- 11446957
TI  - [Coronary revascularization with mammary artery: two better than one?].

PMID- 11446958
TI  - [Prognosis of patients admitted to the coronary or intensive care unita after an
      out of hospital episode of sudden death].
AB  - INTRODUCTION AND OBJECTIVE: Out of hospital sudden death constitutes a major
      sanitary problem. Early diagnosis and treatment are considered as the most
      important factors related with short term prognosis. However, there is little
      information about the outcome of patients admitted to the hospital after a
      successful recovery from an episode of sudden death outside the hospital. The
      objective of this study was to analyze the prognosis of patients who initially
      recovered after an episode of out-of-hospital cardiac arrest and who were
      admitted to the coronary or intensive care unit. PATIENTS AND METHODS: The
      clinical characteristics and outcome of 110 consecutive patients admitted to the
      coronary and intensive care units after an episode of extrahospital sudden death,
      who initially recovered with success, were retrospectively studied. RESULTS: A
      total of 33 (30%) patients were discharged alive and without severe neurological
      damage, 67 (61%) patients died before discharge from hospital and 77 (70%) died
      or presented severe and permanent neurological damage. The latter group versus
      those who survived was older (63.6 +/- 13.5 vs 55.2 +/- 12.6 years old; p <
      0.006) and had a longer delay in the beginning of cardiopulmonary resuscitation
      (8.3 vs 2.8 min.; p < 0.01). Mortality or severe neurological damage rate was
      higher in the group of those who had asystolia than in those with ventricular
      fibrillation in the first ECG (84% vs 55%), in those who arrived to the hospital
      unconscious (73.7% vs 15.4%) and in those who arrived in functional class IV (81%
      vs 16.6%). CONCLUSIONS: Up to 30% of the patients admitted after an episode of
      extrahospital cardiac arrest were discharged alive and without severe
      neurological damage. Advanced age, functional class IV and the delay of
      cardiopulmonary resuscitation are related to a unfavorable outcome.

PMID- 11446959
TI  - [Clinical profile of idiopathic paroxsysmal atrial fibrillation. (FAP registry)].
AB  - OBJECTIVE: To assess the relative frequency and clinical profile of paroxysmal
      lone atrial fibrillation in comparison with that of secondary atrial
      fibrillation. PATIENTS AND METHOD: A prospective multicenter study (FAP Register)
      was designed to include 300 patients with symptomatic paroxysmal atrial
      fibrillation admitted to the emergency ward of 11 secondary hospitals of
      Catalonia. RESULTS: Lone atrial fibrillation was found in 67 patients (22.3%)
      while systemic hypertension was present in 33.7% of the cases; mitral or aortic
      valvular disease in 12% and coronary heart disease in 9.7%. As compared with
      patients with evidence of cardiac or systemic etiology, patients with isolated
      paroxysmal atrial fibrillation were younger (mean age of 55 vs 65 years of age; p
      = 0.0001), dyspnea was less frequent (p = 0.007); had a tendency to appear at
      night; left atrial size was smaller (p < 0.001) and response to treatment of
      sinusal rhythm was not different. CONCLUSIONS: Relative frequency of paroxysmal
      lone atrial fibrillation was only second to hypertension, which appears to be the
      most important pathogenic factor in our population. The clinical profile shows
      similarities in secondary fibrillation

PMID- 11446960
TI  - [Ventricular arrhythmias induced by appropriate antibradycardia pacing in
      patients with implantable defibrillators].
AB  - INTRODUCTION AND OBJECTIVES: The induction of ventricular arrhythmias by
      appropriate antibradycardia ventricular pacing in patients with implantable
      cardioverter defibrillators has been reported in only a few cases. The aim of
      this study was to assess the incidence, characteristics and management of these
      episodes. METHODS: The follow-up records of 180 patients with implantable
      cardioverter defibrillators with intracardiac electrogram storage were reviewed.
      Pacing induced episodes were defined as those occurring immediately after an
      appropriate paced stimulus in a patient with sporadic paced beats. We assessed
      the number and type of episodes, mode of onset, therapy administered and the
      efficacy of different prevention measures. RESULTS: Pacing induced episodes were
      found in 9 patients (5%). Seven received device administered therapy which was
      effective in all cases. One to 95 episodes were observed per patient, of which
      138 were monomorphic ventricular tachycardias and 20 polymorphic ventricular
      tachycardia/ventricular fibrillation episodes. All were induced by a paced
      ventricular beat after a post-extrasystolic pause or after long RR intervals
      during atrial fibrillation. Pacing induced arrhythmias were prevented by changing
      the pacing rate or hysteresis in 3 out of 6 patients and by decreasing the
      stimulus energy in 3 out of 3. Antibradycardia pacing function was disabled in 4
      patients. CONCLUSIONS: Ventricular arrhythmias induced by appropriate
      antibradycardia ventricular pacing are relatively common in patients with
      implantable cardioverter defibrillators. Effective prevention can be achieved in
      most cases by changing the pacing rate or the pacing stimulus energy, however in
      selected cases the antibradycardia function may be disabled.

PMID- 11446961
TI  - [Characteristics of acute myocardial infarction patients treated with mechanical
      ventilation. Data from the ARIAM Registry].
AB  - INTRODUCTION: Scarce information is available about the use, clinical course and
      follow-up of patients with acute myocardial infarction treated with mechanical
      ventilation. PATIENTS AND METHOD: Historical cohort study of patients with acute
      myocardial infarction, included in Spanish registry ARIAM. Differences in
      clinical characteristics and prognosis from patients treated with or without
      mechanical ventilation were compared. RESULTS: Three hundred and thirty-three of
      the 4143 patients (8.1%) with acute myocardial infarction were treated with
      mechanical ventilation. Treated patients were older, more frequently female, and
      had more frequently reinfarcts, anterior infarction, Killip III and IV, and
      higher creatine phosphokinase peak. Diabetes and high blood pressure were more
      frequent in those in which the technique was applied. They had a higher mortality
      at the coronary care unit (65.7 vs 5.1%; p < 0.001) than the non-ventilated
      patients. In multivariate analysis, creatine phosphokinase peak levels higher
      than 1.200 units/ml, Killip III and IV, and an infarction localization different
      to inferior were independent predictors of mechanical ventilation application.
      The 220 treated patients who died were older, more frequently female, had been
      more frequently admitted to the coronary unit, and had Killip IV whereas Killip
      III was more frequent among survivors. In multivariate analysis, restricted to
      patients treated with mechanical ventilation, Killip III was an independent
      predictor of survival with an odds ratio for mortality of 0.26 (CI 95%: 0.09
      0.77). CONCLUSIONS: Mechanical ventilation is a vital support technique employed
      in a significant number of complicated acute myocardial infarction patients. The
      high mortality of these patients was related to more extended myocardial
      infarction and a worse clinical state.

PMID- 11446962
TI  - [Angiographic correlates of the high-risk criteria for conventional exercise
      testing and the Duke treadmill score].
AB  - OBJECTIVE: To compare the sensitivity, the specificity, the positive and negative
      predictive value and the predictive accuracy of the Duke Treadmill Score, the
      Spanish Society of Cardiology (SEC) and American College of Cardiology/American
      Heart Association (ACC/AHA) high-risk criteria for exercise testing in the
      detection of left main disease, three vessel disease and two vessel disease
      involving the proximal left anterior descending artery. PATIENTS AND METHOD: A
      cohort of 199 patients (age 75 years) consecutively admitted to hospital for
      unstable angina was studied. All patients underwent an exercise stress test and
      coronariography. RESULTS: The SEC high-risk Criteria showed a sensitivity of
      69.2% and a specificity of 49.0%. The ACC/AHA high-risk Criteria demonstrated a
      sensitivity of 98.1% and a specificity of 23.8% and the Duke Treadmill Score
      presented a sensitivity of 30.8% and a specificity of 90.5%. In patients with
      moderate risk in the Duke Treadmill Score we found a sensitivity of 62.9% and a
      specificity of 39.8% for the SEC high-risk criteria, while the ACC/AHA high-risk
      Criteria presented a sensitivity of 100.0% and a specificity of 5.8%.
      CONCLUSIONS: The ACC/AHA high-risk Criteria showed a higher sensitivity while the
      Duke Treadmill Score presented a higher specificity for the detection of left
      main disease, three vessel disease and two vessel disease involving the proximal
      left anterior descending artery. The ACC/AHA and SEC high-risk Criteria were
      found to be very useful in the group of patients with moderate risk in the Duke
      Treadmill Score.

PMID- 11446963
TI  - [Clinical results of double versus single mammary artery myocardiac
      revascularization: 15 years of follow-up].
AB  - INTRODUCTION: Use of the left internal mammary artery to bypass the left anterior
      descending coronary artery reduces cardiac events and increases survival.
      However, there is some controversy as to the benefits of using both mammary
      arteries. OBJECTIVES: To assess the long-term outcome of the use of both mammary
      arteries in comparison with the use of only one. PATIENTS AND METHOD: A
      retrospective cohort study with a mean follow-up of 9.0 +/- 4.2 years was
      performed including 108 patients consecutively revascularized using both mammary
      arteries (II) and 108 patients randomly chosen in whom one mammary artery (I) was
      used for this purpose. RESULTS: Both groups were similar. There were no
      differences between the groups in operative morbidity or mortality. The survival
      at 10 years was similar (II: 84.61 +/- 4%; I: 85.18 +/- 3.8%), whereas recurrence
      of angina (II: 29.63 +/- 5.3%; I: 47.55 +/- 5.6%) (p = 0.012), the requirement
      for percutaneous angioplasty (II: 3.98 +/- 2%; I: 12.99 +/- 4.1%) (p = 0.009) and
      cardiologic events (II: 33.48 +/- 5.5%; I: 48.48 +/- 5.5%)(p = 0.022) were all
      lower in the group in which both mammary arteries were used. In the multivariate
      analysis, the use of both mammary arteries was an independent protective factor
      against angina recurrence (RR = 0.55), angioplasty (RR = 0.18) and cardiologic
      event (RR = 0.60). CONCLUSIONS: The use of both mammary arteries for
      revascularization does not increase operative morbidity. Since this procedure
      acts as an independent factor against angina recurrence, angioplasty and
      cardiologic event

PMID- 11446964
TI  - [Doxazosin and soluble guanylate cyclase in a rat model of hypertension].
AB  - BACKGROUND: Although different studies have evaluated the ability of endothelial
      cells to produce NO in the setting of the endothelial dysfunction associated with
      hypertension, less it is known about the soluble guanylate cyclase system. AIM:
      To analyze the level of expression of sGC in the vascular wall in Stroke-prone
      spontaneously hypertensive rats (SHRSP). Moreover, the effect of treatment with
      an alpha1 adrenergic antagonist, doxazosin, on sGC expression was also evaluated.
      METHODS: The study was performed in 24 untreated 20-week-old SPSHR and 12 SPSHR
      treated orally with doxazosin (10 mg/Kg bw/day; for 15 days). A group of
      normotensive Wistar-Kyoto (WKY) rats were used as controls (n = 12). RESULTS:
      Isolated aortic segments from SHRSP showed impaired response to SNP. Doxazosin
      treatment prevented impaired vasodilatory response to SNP. Expression of the
      beta1 sGC in the vascular wall of SHRSP determined by Western blot and
      immunohistochemistry was markedly reduced with respect to that of WKY. Doxazosin
      treatment increased of beta1 sGC expression in treated SHRSP particularly at the
      medium level with respect to that of untreated SHRSP. CONCLUSION: SHRSP showed
      reduced expression of beta1 sGC in the vascular wall and an impaired vasodilator
      response to SNP which improved with doxazosin treatment. These results suggest
      the role the sGC system may play in the global treatment of endothelial
      dysfunction.

PMID- 11446965
TI  - [Guidelines of the Spanish Society of Cardiology on requirements and equipment in
      electrophysiology].
AB  - Due to the enormous qualitative and quantitative evolution that clinical
      electrophysiology has experienced over the past years, specific Units dedicated
      to the management of patients with cardiac arrhythmias have been created. In
      these guidelines, the minimum technical and human needs of an Arrhythmia Unit are
      discussed.

PMID- 11446966
TI  - [Clinical trials reported at the 50th Annual Congress of the American College of
      Cardiology (Orlando, March 18-21, 2001)].

PMID- 11446967
TI  - [Angiographic imaging in a case of penetrating aortic ulcer].

PMID- 11446968
TI  - [Coronary ischemia caused by pseudoxanthoma elasticum and myocardial
      revascularization with double arterial graft].
AB  - We present a case of an 18 year-old woman with pseudoxanthoma elasticum, who had
      a biopsy taken from a lesion. Although she was asymptomatic, we tried to rule out
      myocardial ischemia with a treadmill and cardiac gammagraphy with Talio. The
      isotopic studies and the ergometry were positive and the patient underwent
      coronariography. This study showed a severe triple-vessel disease. We did an
      angiography of the supraaortic arteries, mamarian artery, and mesenteric artery.
      These studies showed no obstructive lesions. The treatment of patient was a
      double by-pass with internal mammary artery and one by-pass with safena vein
      grafts with satisfactory results.

PMID- 11446969
TI  - [Coordination between primary and cardiological care: the opinion of the family
      doctor].
AB  - OBJECTIVE: To analyse the relationship between Primary and Cardiological Care
      from the perspective of family physicians. METHODS: A descriptive-crossover study
      was carried out by a questionnaire sent by mail to a sample of 384 doctors
      systematically selected from the database of the College of Physicians of Madrid.
      RESULTS: One hundred forty-eight physicians (38.5%) answered the questionnaire,
      75% of whom saw more than 30 patients/week with cardiovascular risk factors and
      more than 10 patients/week with cardiac syndromes, in the following order:
      ischaemic heart disease, heart failure, arrhythmias, valvular disease, cor
      pulmonale and others. Ninety percent of the physicians refer less than 10
      patients/month to cardiologists, with a time delay of greater than a month in 50%
      of the cases. The document used for referral is the consultation form (98%) that
      is always or frequently answered. The quality of the cardiologist's report is
      either good or excellent in 50% of the cases. Accessibility to electrocardiograms
      and thorax x-rays by family doctors is of 99.3%. Family physicians have a very
      positive opinion regarding the need for hospital collaboration in their
      continuous training and coordination with cardiologists.

PMID- 11446970
TI  - [Heart failure as the initial cardiac manifestation of Steinert's myotonic
      dystrophy].
AB  - The relationship between neuromuscular diseases and the heart has been well known
      for many years. Cardiac lesions tend to involve the specialized conducting
      system. We report the case of a 36-year-old male diagnosed with Steinert's
      myotonic dystrophy whose initial cardiovascular symptom was heart failure and not
      symptoms related to alterations of the specialized conducting system.

PMID- 11446971
TI  - [Refractory angina caused by subclavian-coronary steal syndrome treated with
      angioplasty and stent].
AB  - The coronary-subclavian steal syndrome is a rare cause of recurrent myocardial
      ischemia in patients who have undergone left internal mammary-coronary artery
      bypass grafting. A significant left subclavian artery stenosis proximal to its
      origin, can result in an impaired or reversed flow in this graft and myocardial
      ischemia. We describe the case of a woman aged 76 who had undergone myocardial
      revascularization seven months before, and presented refractory angina with
      severe electrocardiographic ischemia in the left anterior descending artery
      territory. Arteriography confirmed this syndrome and the patient was successfully
      treated with percutaneous transluminal angioplasty and placement of two stents in
      the left subclavian artery. We review the clinical management, diagnostic methods
      and therapeutic options used in the subclavian-coronary steal syndrome.

PMID- 11446972
TI  - [Cor triatriatum associated with Wolff-Parkinson-White syndrome].
AB  - Several anatomic anomalies have been associated with the Wolff-Parkinson-White
      syndrome. However, its association with cor triatriatum has never been previously
      established. We present a case report on a 34-year-old woman patient with
      paroxysmic palpitations and data of ventricular preexcitation seen on
      electrocardiogram. The presence of non-obstructive cor triatriatum was observed
      during echocardiographic valoration prior to radiofrequency catheter ablation.

PMID- 11446973
TI  - [Indications of pre-hospital fibrinolysis].

PMID- 11446977
TI  - Palatability and intake relationships in free-living humans: the influence of
      heredity.
AB  - The heritability of the before and after meal self-ratings of palatability and
      their relationship to food intake was investigated with 86 identical and 78
      fraternal same-sex and 51 fraternal mixed gender adult twin pairs who were paid
      to maintain 7-day food intake diaries. From the diary reports, the total and meal
      intakes of food energy and the amounts of the macronutrients ingested were
      estimated. Participants rated the meals for palatability on a 7-point (Bad -
      Good) scale both before and after eating. Linear structural modeling was applied
      to investigate the nature and degree of genetic and environmental influences and
      revealed significant genetic influences on subjective palatability both before
      and after the meals. In addition, the relationship between palatability and
      intake was influenced by the genes. Significant dominance genetic effects were
      found for the change in meal size between low-moderate and high palatability
      meals, indicating that palatability and it's relationship with intake are to some
      extent heritable. This suggests that the level of subjective experience and the
      individuals responses to them are influenced by the genes and become part of the
      total package of genetically determined physiological, socio/cultural, and
      psychological processes that regulate energy balance.

PMID- 11446978
TI  - Estimated dietary isoflavone intake of Korean population based on National
      Nutrition Survey.
AB  - The dietary isoflavone intake of the Korean population was estimated based on
      data from the Korean National Nutrition Survey conducted in 1995, which included
      3224 male and 3475 female subjects with a wide age range. Data on the isoflavone
      content of soybeans and their products were collected from a literature survey of
      Korean journals. This information was then screened based on the methodological
      validity, compared with values reported in international journals, and an average
      value adopted for each food. Thereafter, the total isoflavone intake per capita
      was estimated as 14.88 mg/d, which was attributed to genistein (7.32 mg),
      daidzein (5.81 mg), and glycitein (1.75 mg). Soybeans and three traditional soy
      foods (tofu, soybean paste, soybean sprouts) contributed to more than 94% of the
      total isoflavone intake of the Korean population. Slight differences in the
      isoflavone intake level and pattern were observed between the various residential
      areas. The rural and urban isoflavone intakes were estimated at 15.18 and 14.85
      mg per capita, respectively. Rural residents were more dependent on soybeans than
      processed soy products for their isoflavone intake, while urban residents
      extracted more isoflavones from tofu, compared to their rural counterparts. The
      total isoflavone intake reported in this study may be underestimated, as other
      products containing soyflour and soy protein were not accounted for.

PMID- 11446979
TI  - An assessment of c9,t11 linoleic acid intake in a small group of young Canadians.
AB  - Dietary conjugated linoleic acid (CLA) in ruminant foods has potential health
      benefits. CLA content in dairy and meat products is known. However, CLA intake
      has not been documented from records of food intake in free-living Canadian
      subjects. Intake of the cis-9, trans-11-octadecadienoic acid (c9,t11 CLA) isomer
      was estimated for 22 free-living Canadians by analyzing two seven-day diet
      records taken six months apart. Intake of c9,t11 CLA did not differ between the
      two periods during which the food records were collected. Average intake was
      determined to be 94.9 +/- 40.6 mg/day ranging between 15-174 mg/day. Intake of
      the c9,t11 isomer of CLA when expressed as mg CLA per unit of energy consumed was
      significantly correlated to intake of saturated fat (r = 0.62, P < 0.002) and not
      significantly correlated to intake of total fat (r = 0.39, P < 0.08). Daily
      c9,t11 CLA intakes varied considerably with approximately 50% of the intakes
      falling below the 20th percentile for average level of intake per day.

PMID- 11446980
TI  - Plasma homocysteine concentrations of Indonesian children with inadequate and
      adequate vitamin B-6 status.
AB  - The objective of the study was to determine the usefulness of utilizing plasma
      homocysteine concentrations as an indicator of vitamin B-6 status in subjects
      with inadequate and adequate status as demonstrated by currently accepted
      indicators. Plasma homocysteine concentrations of 77 third-grade Indonesian
      children (aged 8-9 y; boys and girls) were measured. About a quarter of these
      subjects had inadequate vitamin B-6 status as indicated by their plasma pyridoxal
      5'-phosphate concentrations, erythrocyte alanine aminotransferase activity
      coefficients, and reported dietary vitamin B-6 intakes. No significant
      differences in plasma homocysteine concentrations were observed between subject
      groups shown to have inadequate and adequate vitamin B-6 status using currently
      accepted indicators. Plasma homocysteine concentrations of the subjects were not
      correlated with values for other vitamin B-6 indices. Plasma homocysteine
      concentration was not an indicator of vitamin B-6 status in these children, as it
      did not differentiate between children shown otherwise to have inadequate and
      adequate status of the vitamin.

PMID- 11446981
TI  - Nutrient intakes and iron status of elderly men and women.
AB  - Nutrient intake including iron and iron status indicators were investigated in 96
      elderly subjects. Subjects were divided into 6 groups based on the sex and age.
      Each subject completed a 24-h diet recall and semi-quantitative food frequency
      questionnaire. Iron status indicators were measured. Body iron stores were
      calculated. The mean iron intake was higher than the current Taiwan Recommended
      Daily Nutrient Allowance of 10 mg in all groups. However, iron intake did not
      correlate with iron status indicators in any groups. Body iron stores
      significantly positively correlated with plasma ferritin (p < 0.05). One man in
      65-69 y group, 2 men in 70-74 y group, 3 women in 65-69 y group, and 2 women in
      70-74 y group were identified iron deficiency anemia. Elderly subjects had
      sufficient iron intakes, but iron deficiency still occurred in the elderly.

PMID- 11446982
TI  - Dietary intake of elite figure skating dancers.
AB  - The main objective of the present study was to examine the dietary intake and
      physiological status of members of the US National Figure Skating Dance Team.
      Study participants included seven female and seven male figure skating dance
      pairs. Three-day food records were collected from each dancer and analyzed using
      a computerized nutrient database. Height, body weight and skinfold measurements
      were completed on each dancer. Body fat was estimated using the Jackson et al
      prediction equations. Fasting blood samples were collected for biochemical
      analysis. Total energy intake of female dancers (1416 kcal/d, 339 kjoules/day)
      was considerably lower than the dietary recommendations, while the male dancers
      appeared to have adequate energy intake (2837 kcal/d, 679 kjoules/day).
      Carbohydrate intake of both male and female dancers was below the
      recommendations, 44% and 51%, respectively, whereas total fat and protein intake
      of both male and female dancers were higher than the dietary recommendations. All
      dancers met at least 2/3(rd) of the dietary recommendations for all micro
      nutrients, except folate and zinc intake of the female dancers, which were 68%
      and 62% of the recommended values. Although, blood lipid concentrations and other
      physiological parameters of the overall group were within normal ranges, two of
      the dancers (14% of the dancers) had elevated blood cholesterol concentrations
      and low iron status. The results of the present study suggest that these elite
      figure skating dancers, especially females, may not be consuming adequate amounts
      of energy-yielding nutrients and those that influence bone health. Future studies
      are needed to examine the effects of nutritional status on performance of these
      figure skating dancers and to develop strategies to improve the nutritional
      status of these elite dancers.

PMID- 11446983
TI  - Trehalose suppresses lipopolysaccharide-induced osteoclastogenesis bone marrow in
      mice.
AB  - We have previously shown that trehalose suppresses bone loss in ovariectomized
      (OVX) mice by way of inhibiting osteoclast differentiation in bone marrow. Also,
      trehalose inhibits the secretion of interleukin-6 in bone marrow cell cultures,
      resulting in a decrease in osteoclast formation. In this study, we examined the
      effect of trehalose on osteoclastogenesis using another model of bone resorption,
      namely lipopolysaccharide (LPS)-stimulated osteoclast induction. Mice were given
      trehalose (1g/kg) by gastric intubation for 5 consecutive days, and 24 hours
      later, 14 mg/kg of LPS was injected intraperitoneally. Trehalose significantly
      suppressed LPS-induced tumor necrosis factor (TNF)-alpha production after 90 min
      and decreased the number of osteoclasts in the bone marrow 48 hours after LPS
      injection. These results indicate that trehalose suppresses excessive
      osteoclastogenesis not only in OVX mice but also in a LPS-induced bone resorption
      mouse model and further suggest that the latter finding may be mediated at least
      in part through a decrease in TNF-alpha production.

PMID- 11446984
TI  - Lymphatic transport of fat in rats with normal- and malabsorption following
      intake of fats made from fish oil and decanoic acid. Effects of triacylglycerol
      structure.
AB  - Fish oils contain essential polyunsaturated fatty acids of the n-3 family. In fat
      malabsorption the n-3 fatty acids are poorly absorbed. Absorption may be improved
      by modifying the fatty acid profile of fish oil through interesterification with
      medium chain fatty acids. We examined the absorption of fish oil interesterified
      with decanoic acid in rats with normal- and malabsorption compared to a physical
      mixture and the fish oil itself. The interesterified fats were: 1) a
      regiospecific fat with decanoic acid located mainly in the sn1/3-positions and a
      long chain fatty acid from fish oil in the sn2-position, 2) a fat with a random
      distribution of fatty acids in all positions of the triacylglycerol. The main
      mesenteric lymph duct was cannulated for collection of lymph. In the malabsorbing
      rats the common bile duct was cannulated as well to divert both pancreatic juice
      and bile. The fatty acid composition in lymph samples collected for 24 hours was
      determined. Accumulated transport of n-3 fatty acids from fish oil was improved
      in malabsorbing rats and recoveries of fatty acids after 24 hours were improved
      in both rats with normal- and malabsorption administered the randomized fat
      compared to fish oil.

PMID- 11446985
TI  - mRNA expression for insulin-like growth factor 1, receptors of growth hormone and
      IGF-1 and transforming growth factor-beta in the kidney and liver of Zucker rats.
AB  - Kidney dysfunction and mesangial enlargement are consequences of obesity found in
      Zucker rats. This study examines some of the early mechanisms by which the
      kidneys of Zucker rats undergo these changes. Our study shows that the glomerular
      planar area in the genetically obese Zucker rat undergo enlargement as early as
      12 weeks of life, compared to the lean controls. This suggests mesangial
      proliferation is already occurring at this time, earlier than previously shown.
      The mRNA expression for IGF-I, and GHR in the kidney and liver of the obese
      Zucker rats were significantly reduced compared to the lean controls. However,
      the mRNA of the IGF-IR was significantly elevated in the kidney of the obese
      Zucker rats. The increase in kidney IGF-1R mRNA in the obese Zucker rat may
      suggest an increase in IGF-1 binding leading to the kidney hypertrophy observed
      in these rats.

PMID- 11446986
TI  - Influence of age and ovariectomy on the hypocholesterolemic effects of dietary
      taurine in rats fed a cholesterol-free diet.
AB  - The effects of taurine feeding on plasma cholesterol concentrations and fecal
      bile acid excretion were examined in young and aged male and female rats (5 weeks
      and 10 months old respectively), the latter either ovariectomized (ovx) or sham
      operated. The rats were fed a cholesterol-free diet (C diet) or a cholesterol
      free taurine-supplemented diet (T diet; C + 5% taurine) for 28 days. In males,
      plasma cholesterol concentrations and fecal bile acid excretion were higher and
      lower, respectively, in aged rats than in young rats, but were not affected by
      feeding with the T diet. In female rats, plasma cholesterol concentrations were
      higher in aged rats than in young rats and higher in ovx-rats than in sham
      operated rats. In contrast to male rats, plasma cholesterol concentrations were
      lower in female rats fed the T diet than in those fed the C diet. Plasma
      cholesterol concentrations were increased in aged ovx-rats, but decreased by
      feeding with the T diet. Fecal bile acid excretion was higher in rats fed the T
      diet than in those fed the C diet. Thus, these data indicate that the
      hypocholesterolemic effect of taurine is greater in aged rats than in young rats.

PMID- 11446987
TI  - Arginine-genotype interactions and immune status.
AB  - The effects of arginine on selective immune responses were investigated in a high
      arginine-requiring (HA) and low arginine-requiring (LA) strain of chickens.
      Female chickens from these strains were fed diet containing a nutritionally
      inadequate level of arginine (0.53% arginine diet) or a surfeit level of arginine
      (1.53% arginine diet) for 2 weeks. Compared to LA chickens, HA chickens showed a
      higher feed efficiency, body weight gain, and relative thymus and spleen weights
      with L-arginine supplementation (p < 0.05). In both HA and LA chickens, a
      deficiency of arginine significantly decreased the delayed-type hypersensitivity
      response (p < 0.05) and nitric oxide (NO) production from macrophages. Chickens
      of the HA strain had higher NO production than those of LA strain with E. coli
      lipopolysaccharide (LPS) activation. This study indicates that dietary arginine
      concentration influences the immune status of chickens and that strains that
      differ in arginine requirements for growth may differ in their arginine needs for
      immune function.

PMID- 11446988
TI  - Serum leptin levels in cattle with different nutritional conditions.
AB  - The role of leptin as an energetic state indicator in cattle was evaluated
      correlating different nutritional conditions and serum leptin levels. Two
      experiments were developed. Experiment I: Polled Hereford heifers were fed in
      optimum conditions and assigned randomly to one of three treatment diets:
      grazing, grazing plus supplementation and feedlot. Experiment II: cattle were
      subjected to feed restriction (R). Serum leptin levels were measured at pre and
      post-feeding moments. Using serum free fatty acid (FFA), beta-OH Butyrate (beta
      OHB) and protein concentration as serum energetic indicators in both experiments.
      In experiment I leptin values were significantly different between pre and post
      feeding moments, similar differences were found among groups when the pre-feeding
      and post-feeding values were compared. These differences may be considered as
      changes associated to the control of food intake. In experiment II, the serum
      leptin levels in Group R were significantly lower. The poor energetic status of
      animals from group R was demonstrated by the serum FFA, beta-OHB and protein
      concentrations. These results suggest that the energetic status of animals is
      correlated with the serum leptin levels, tending to maintain the energetic
      homeostasis.

PMID- 11446989
TI  - The influence of dietary proteins on colon cancer risk.
AB  - Experimental evidence is accumulating from animal models and in vitro data which
      shows that dietary proteins can influence cancer expression, some having a
      promotional influence, others a preventative effect relative to an arbitrarily
      established standard diet. This result will to a degree be determined by the
      nature of the cancer model under study. Dairy proteins have been shown to be
      relatively protective when compared with defatted soybean meal and cooked red
      meat in the rat dimethylhydrazine-induced (DMH) colon cancer model. Some
      epidemiological evidence supports these experimental observations. Both protein
      and fat appear to be influencing outcome, with potential for interactive effects.
      A number of possible mechanisms have been postulated as to how these proteins and
      closely associated factors could be influencing colon cancer risk, an area that
      deserves more investigation. Combinations of foods such as dairy foods with
      cereals and/or probiotic bacteria provide potentially interesting alliances in
      reducing colon cancer risk. The combining of relatively protective agents
      deserves more investigation as to its potential, in devising functional foods and
      diets worthy of further evaluation, in animal models of cancer, and human
      intervention studies using relevant endpoint markers.

PMID- 11446990
TI  - Thermal treatment improves nutritional quality of pea seeds (Pisum sativum L.)
      without reducing their hypocholesterolemic properties.
AB  - The effects of isoproteic isoenergetic diets containing raw (RP) or extruded (EP)
      pea (Pisum sativum, cv. Ballet) seed meal on nutritional performance and serum
      lipids, amino acids and enzyme levels in growing rats were studied in two 15 d
      feeding experiments. Food intake and growth were greatly reduced in animals fed
      unsupplemented RP or EP. Both parameters were improved by addition of amino acids
      to the diets. Growth, apparent N digestibility, biological value and net protein
      utilisation values for supplemented (SRP) raw peas were however inferior to those
      for controls whilst with supplemented (SEP) extruded peas the values were similar
      to control levels. SRP and SEP also greatly reduced serum total cholesterol, LDL
      (VLDL) and cholesterol/HDL ratio. This may have been linked to the lower plasma
      lysine:arginine ratio. SRP and SEP increased kidney and adrenal weights and
      reduced liver weight. SRP stimulate pancreatic growth but SEP did not. Analysis
      of serum proteins and enzymes suggested these tissue changes did not lead to
      chronic disruption to gut or systemic metabolism. Extrusion treatment of peas
      improved their nutritional quality but did not reduce their hypocholesterolemic
      properties.

PMID- 11446991
TI  - Effects of dietary galactose and fructose on rats fed diets marginal or adequate
      in copper for 9-21 months.
AB  - This study was designed to monitor the metabolic differences after feeding
      starch, galactose and fructose diets with adequate or marginal copper levels to
      normal male rats over a period of 9-21 months. Two hundred and forty-five
      weanling male Sprague-Dawley rats weighing approximately 50-60 g were randomly
      divided into one of the eight dietary groups. All diets were either Cu marginal
      (1.5 &mgr;g/g diet) or adequate (5-6 &mgr;g/g) with 627 carbohydrate (g/kg diet)
      as starch; 500 galactose and 127 starch; 500 fructose and 127 starch; or 400
      galactose and 227 fructose. Glycated hemoglobin, ceruloplasmin oxidase activity,
      hematocrit, and plasma glucose, cholesterol, and triglyceride were measured in 72
      rats after nine months. Galactose-fed rats had the lowest (P < 0.0001) body
      weights. Severe mortality rates were found in galactose-fructose-marginal Cu-fed
      rats. Marginal Cu deficiency significantly (P < 0.0001) reduced hepatic copper
      and increased hepatic Fe in all carbohydrate groups. Ceruloplasmin activity of
      the rats fed the marginal Cu and fructose-containing diets declined to
      undetectable levels and plasma cholesterol levels increased. Glycated hemoglobin
      was significantly (P < 0.001) increased in the galactose-fed rats compared to
      fructose or starch-fed rats regardless of dietary copper concentration. The data
      suggest that dietary galactose and fructose exacerbate effects of long term
      marginal Cu intake including hypertrophy of liver, heart and kidney,
      hyperlipidemia, and increased mortality.

PMID- 11446992
TI  - Identification of differentially expressed genes by the cDNA-AFLP technique
      during dehydration of almond (Prunus amygdalus).
AB  - We analyzed several genes that were strongly expressed in response to dehydration
      of almond (Prunus amygdalus (L.) Batsch) as a means of identifying and
      determining the genetic basis of mechanisms involved in drought tolerance. The
      advantages of using almond as a model system for studying dehydration tolerance
      in woody species include its small diploid genome and its adaptation to drought.
      We used the differential expression technique cDNA-AFLP (amplified restriction
      fragment polymorphism derived technique for RNA fingerprinting) to identify
      transcripts that accumulated in mature embryos and in in-vitro-cultured plantlets
      subjected to desiccation or abscisic acid (ABA) treatment. The reverse northern
      approach was used to differentiate between true differential bands and false
      positives. Some of the predicted polypeptides exhibited similarity to published
      protein sequences, including a transporter of nitrogenous compounds, a 1-acyl-sn
      glycerol-3-phosphate acyl transferase, a low molecular weight heat shock protein,
      a cysteine proteinase and a constitutively expressed proline-rich protein. We
      also compared the levels of expression of the identified genes in leaves of young
      trees of eight almond cultivars differing in drought tolerance.

PMID- 11446993
TI  - Response to seasonal drought in three cultivars of Ceratonia siliqua: leaf growth
      and water relations.
AB  - Responses of leaf growth and leaf water relations to seasonal drought were
      monitored during two successive years in three cultivars (Galhosa, Espargal and
      Mulata) of Ceratonia siliqua L. growing in the field in southern Portugal. Leaf
      water relations of fully expanded leaves were characterized by pressurea  volume
      analysis, and morphometric measurements of petiolar xylem were made. The three
      cultivars differed with respect to onset of leaf initiation. In Galhosa, there
      was a sharp peak of leaf initiation in June that was immediately followed by a
      period when leaf expansion rates were highest. The onset of leaf growth occurred
      earlier in Espargal and Mulata than in Galhosa, and both cultivars continued
      producing new leaves throughout the summer period. The diurnal pattern of water
      relations in recently expanded leaves indicated that, during midsummer, Galhosa
      was the only cultivar in which leaf water potential did not fall below the turgor
      loss point and leaf relative water content remained above 90%. The occurrence of
      osmotic adjustment in recently expanded leaves of Galhosa was not demonstrated
      conclusively. However, during the dry season following leaf formation, a seasonal
      decrease in osmotic potential sufficient to maintain turgor was detected in 1
      year-old leaves of Galhosa but not in 1-year-old leaves of the other cultivars.
      Among cultivars, Galhosa petioles had the widest xylem conduits, which may partly
      explain why midday leaf water potential in Galhosa never decreased below -2.0 MPa
      even at the end of the summer drought.

PMID- 11446994
TI  - Changes in polyamines, auxins and peroxidase activity during in vitro rooting of
      Fraxinus angustifolia shoots: an auxin-independent rooting model.
AB  - Among shoots of Fraxinus angustifolia Vahl raised in vitro, 76% rooted after
      culture on root induction medium for 5 days in darkness followed by culture on
      root expression medium for 15 days in light. The addition of 20.7 microM indole
      butyric acid (IBA) to the root induction medium did not significantly increase
      the rooting percentage (88%). Putrescine, spermidine, cyclohexylamine (CHA) and
      aminoguanidine (AG) enhanced rooting up to 100% (98.66% for AG), when applied
      during root induction in the absence of IBA, otherwise these compounds inhibited
      rooting, as did spermine and difluoromethylornithine (DFMO) +
      difluoromethylarginine (DFMA). The root induction phase was characterized by a
      temporary increase in endogenous free indole-acetic acid (IAA) and putrescine
      concentrations during root induction, whereas the root expression phase was
      characterized by increased peroxidase activity and low concentrations of
      polyamines. These changes were specifically associated with the rooting process
      and did not depend on the presence of exogenous IBA, because application of
      exogenous IBA enhanced the amount of IAA in the cuttings but did not affect
      rooting or the pattern of changes in polyamines and peroxidase. The effects of
      CHA, AG and DFMO + DFMA on endogenous concentrations of auxins and polyamines
      highlight the close relationship between the effects of IAA and putrescine in
      root induction and suggest that polyamine catabolism has an important role in
      root formation and elongation.

PMID- 11446995
TI  - Inducible expression of the heterologous PAL2 promoter from bean in white pine
      (Pinus strobus) transgenic cells.
AB  - To elucidate heterologous promoter function in gymnosperms, we introduced the
      bean phenylalanine ammonia-lyase-beta-glucuronidase (PAL2-GUS) gene fusion into
      white pine (Pinus strobus L.). Over 15 lines were produced and integration of
      Agrobacterium T-DNA was confirmed by Southern analysis. Induction of the reporter
      gene was detected in all of the lines tested following UV illumination. In
      contrast, a weak but constant induction was seen in only a few lines following
      treatment with salicylic acid (SA) or jasmonic acid (JA). However, pretreatment
      of suspension cultures with SA or JA enhanced the induction of PAL2-GUS
      expression by UV irradiation. This specific enhancement or potentiation was
      reduced by 50% by treating the cells with indomethacin, an inhibitor of
      phospholipase activity, suggesting that the observed potentiation of UV induction
      involves the octadecanoid pathway. The UV induction was completely abolished by
      treating the cells with okadaic acid, an inhibitor of phosphatase activity. Thus,
      the induction of the heterologous PAL2 promoter from bean is consistent with the
      induction of phenylalanine ammonia-lyase (PAL) in angiosperms. Furthermore, our
      findings suggest that conifers, although phylogenetically distant to angiosperms,
      share some conserved promoter elements and some signal transduction mechanisms
      for UV-light perception.

PMID- 11446996
TI  - Role of boron in drought resistance in Norway spruce (Picea abies) seedlings.
AB  - Norway spruce (Picea abies (L.) Karst.) seedlings fertilized with boron (B) at
      three rates were grown in a 3:7 mix of forest humus and quartz sand for 18 weeks.
      Half of the seedlings were not watered during the last 9 days of the experiment
      (drought treatment). The role of B in drought resistance was assessed by
      comparing the effects of seedling internal B concentration on the water
      relations, photosynthesis, growth and nutrition of well-watered and drought
      treated seedlings. At the end of the drought treatment, needle B concentrations
      were 7.0 mg x kg(-1) at the lowest B supply rate and 17.5 and 23.5 mg x kg(-1),
      respectively, at the higher supply rates. Seedlings at the lowest B supply rate
      had fewer root tips and mycorrhizas than seedlings at the higher B supply rates.
      Drought treatment had a more pronounced effect on the water relations and net
      photosynthetic rate of seedlings than B treatment. Although seedlings at the
      higher B supply rates lost water more rapidly than seedlings at the low B supply
      rate-leading to faster stomatal closure and decreased photosynthesis-drought did
      not affect their final height, whereas drought reduced height growth of seedlings
      at the low B supply rate.

PMID- 11446997
TI  - Relationships between hydraulic architecture and leaf photosynthetic capacity in
      nitrogen-fertilized Eucalyptus grandis trees.
AB  - We compared the effects of nitrogen fertilization on shoot hydraulic architecture
      and leaf photosynthetic properties of Eucalyptus grandis Hill ex Maiden trees in
      Hawaii. It was hypothesized that water transport capacity would adjust to
      nutrient availability, with leaf specific hydraulic conductivity (kl) increasing
      in fertilized trees in coordination with higher photosynthetic capacity per unit
      leaf area. Trees were grown from seedlings in the field for 10 months at four
      rates of nitrogen (N) fertilization between 0 and 336 kg x ha(-1). Leaf water
      potentials, photosynthetic capacity and kl were measured before whole shoots were
      harvested to determine total growth, leaf area and sapwood density. Mean tree
      height increased from 4 to 5.3 m, stem basal area increased from 27 to 67 cm2 and
      total leaf area increased from 15 to 40 m2 between the lowest and highest rates
      of fertilizer addition. When trees were compared on the basis of leaf nitrogen
      per unit area (N(area)), light-saturated rates of photosynthesis on an area and
      mass basis and the maximum rate of electron transport all increased from 50% to
      more than 100% as N(area) increased from 0.8 to 2.1 g x m(-2). Branch specific
      hydraulic conductivity (ks) and kl increased with height in the crown. However,
      there was no change in branch kl or the ratio of leaf area to sapwood area of the
      whole shoot in response to fertilization, and ks and density of the sapwood were
      unrelated to leaf N(area). In contrast to photosynthesis, stomatal conductance
      did not respond to fertilization, leading to decreased internal carbon dioxide
      partial pressure (p(i)/p(a)) in fertilized plants and similar leaf water
      potentials in all plants. Consistent with the behavior of p(i)/p(a), carbon
      isotope discrimination decreased by 2% with increasing leaf N(area), supporting
      the conclusion that intrinsic water-use efficiency was enhanced by fertilization.
      Increased growth in response to fertilization involved adjustment at the leaf
      level rather than a change in the balance between water transport capacity and
      leaf area. It is proposed that, when there are changes in leaf properties without
      any external change in water availability or evaporative demand, leaf
      photosynthesis and stomatal conductance are partially constrained by the
      hydraulic architecture of the tree.

PMID- 11446998
TI  - Hydraulic conductance in aspen (Populus tremuloides) seedlings exposed to low
      root temperatures.
AB  - Low root temperatures significantly reduced root hydraulic conductivity and
      increased resistance to water flow through the roots of aspen (Populus
      tremuloides Michx.) seedlings. Increased resistance to water flow could not be
      fully explained by the corresponding increase in water viscosity at low
      temperatures. The shapes of Arrhenius plots of root water flow and the activation
      energies were dependent on the direction, sequence and extent of temperature
      change. The Arrhenius plots suggested that the effect of low root temperature on
      root water flow was mediated by an effect on root metabolism. The low root
      temperatures tested did not induce root electrolyte leakage normally associated
      with cell membrane injury. Although a decrease in root temperatures to 7 or 4
      degrees C induced a reduction in stomatal conductance, this reduction lagged the
      decline in root water flow by several hours. In contrast, when soil temperatures
      were raised from 4 or 7 degrees C to 25 degrees C, root water flow presumably
      increased, and stomatal conductance responded rapidly and was temporarily higher
      than before the cold treatment was imposed.

PMID- 11446999
TI  - Estimation of conduit taper for the hydraulic resistance model of West et al.
AB  - The model of West, Brown and Enquist (1999) showed that total hydraulic
      resistance in trees can be independent of path length, provided that vascular
      conduits taper sufficiently. The original model defined the coefficient of taper,
      a bar, in terms of conduit radius and segment number, but segments can be
      difficult to distinguish in old stems. Adhering strictly to the definitions and
      assumptions of West et al., we derived several equations for the estimation of a
      bar based on measurements of tracheary radius and flow path length. However, an
      additional parameter, b, was introduced to permit different models of variation
      in the length of segments along the flow path besides the volume-filling model of
      West et al., including a fixed-length model and intermediate versions. One of the
      new equations was fitted to previously published data for two tree species to
      illustrate the estimation of conduit taper from path-length relations, which
      proved quite sensitive to variation in b. Sampling protocols for improving such
      analyses are suggested.

PMID- 11447000
TI  - Leaf characteristics and chlorophyll concentration of Schyzolobium parahybum and
      Hymenaea stilbocarpa seedlings grown in different light regimes.
AB  - Light in the understory of a forest varies not only with season and solar
      elevation but also with vegetation dynamics. Seedlings of Schyzolobium parahybum
      (Vell) Blake, a fast-growing pioneer species, and Hymenaea stilbocarpa L., a slow
      growing shade-tolerant species, were grown in pots for 90 days in a forest canopy
      gap (full sunlight) or in semi-shade (about 44% of full sunlight) beneath the
      canopy of a secondary forest. Both sites were located in Itaguai, RJ State,
      Brazil. Subsequently, half the seedlings grown in the canopy gap were moved to
      semi-shade and half the seedlings grown in semi- shade were moved to the canopy
      gap. After a further 90 days, seedling dry weight, height, leaf area, specific
      leaf area, leaf area ratio and concentration of chlorophyll a and b were
      measured. In response to increased irradiance, Schyzolobium parahybum responded
      by producing more leaf area, whereas Hymenaea stilbocarpa responded by increasing
      leaf mass per unit area and chlorophyll a concentration.

PMID- 11447001
TI  - Cutaneous malignancies and their management.
AB  - Skin cancer is the most common malignancy occurring in humans, and the incidence
      of basal cell carcinoma, squamous cell carcinoma, and melanoma continues to rise.
      Advances in the diagnosis and treatment of skin cancer have led to more
      successful management of these tumors. A number of options for the treatment of
      skin cancer are available to the patient and physician, allowing for high cure
      rates and excellent functional and cosmetic outcomes.

PMID- 11447002
TI  - Skin anatomy and flap physiology.
AB  - This article focuses on three main areas, which includes an overview of skin
      anatomy, different types of skin flaps and their vascular supply, and several
      aspects of flap biomechanics to allow the surgeon to perform the most adequate
      reconstruction with regard to location and size of defects.

PMID- 11447003
TI  - Management of scalp defects.
AB  - This article presents a systematic approach to the reconstruction of scalp
      defects, which includes a review of the anatomy of the scalp as it pertains to
      reconstruction, and a discussion of the various reconstructive options for scalp
      defects, such as grafts and flaps. Further, scalp flap selection, design, and
      execution are outlined. Finally, adjunctive techniques of tissue expansion and
      hair transplants are included to enhance the final aesthetic result.

PMID- 11447004
TI  - Forehead and temple reconstruction.
AB  - Reconstruction of the forehead and temple region poses special aesthetic
      challenges for maintaining eyebrow symmetry and hairline. The preservation of
      motor and sensory function is also important. There are a wide variety of
      techniques available to the reconstructive surgeon, and these methods are
      compared and discussed with specific reference to the forehead and temple region.

PMID- 11447005
TI  - Reconstructive options for periocular defects.
AB  - Reconstruction of the periorbital area following skin cancer excision requires a
      thorough knowledge of orbital anatomy and eyelid function. Reconstructive
      procedures should maintain the function of periorbital structures while
      attempting to achieve optimal cosmesis. Generally, eyelid reconstruction can be
      considered in terms of the thickness and overall size of the defect. Both the
      anterior and posterior lamella should be restored, and at least one of these
      layers needs to be vascularized. The integrity of the canthal tendons should also
      be addressed. If severed, the tendons should be attached to bony landmarks in
      order to recreate the proper curvature of the eyelid against the globe. Finally,
      defects involving the lacrimal system should be assessed and properly
      reconstituted.

PMID- 11447006
TI  - Cheek repair.
AB  - The cheek, one of the most important facial aesthetic units, adjoins key facial
      structures including the mouth, nose, and eyelids. When undertaking cutaneous
      cheek defect repair, these functional structures must remain undisturbed. Indeed,
      the size, depth, and position of each defect must be critically assessed in
      relation to surrounding donor tissue and landmarks. This article reviews cheek
      anatomy, surface landmarks, and the various surgical options for achieving
      successful aesthetic and functional repair.

PMID- 11447007
TI  - Lip and perioral defects.
AB  - Reconstruction of the lip and perioral region presents a myriad of problems, as
      deformities of this region can produce both aesthetic deformation and functional
      difficulties. This article reviews basic principles of lip reconstruction,
      emphasizing the differences between defects of the upper and lower lip.

PMID- 11447008
TI  - Microbes and microbial toxins: paradigms for microbial-mucosal interactions.
      VIII. Pathological consequences of rotavirus infection and its enterotoxin.
AB  - Rotaviral infection in neonatal animals and young children leads to acute self
      limiting diarrhea, but infected adults are mainly asymptomatic. Recently,
      significant in-roads have been made into our understanding of this disease: both
      viral infection and virally manufactured nonstructural protein (NSP)4 evoke
      intracellular Ca(2+) ([Ca(2+)]i) mobilization in native and transformed
      gastrointestinal epithelial cells. In neonatal mouse pup mucosa models, [Ca(2+)]i
      elevation leads to age-dependent halide ion movement across the plasma membrane,
      transepithelial Cl(-) secretion, and, unlike many microbial enterotoxins, initial
      cyclic nucleotide independence to secretory diarrhea. Similarities between
      rotavirus infection and NSP4 function suggest that NSP4 is responsible for these
      enterotoxigenic effects. NSP4-mediated [Ca(2+)]i mobilization may further
      facilitate diarrhea by signaling through other Ca(2+)-sensitive cellular
      processes (cation channels, ion and solute transporters) to potentiate fluid
      secretion while curtailing fluid absorption. Apart from these direct actions in
      the mucosa at the onset of diarrhea, innate host-mediated defense mechanisms,
      triggered by either or both viral replication and NSP4-induced [Ca (2+)]i
      mobilization, sustain the diarrheal response. This secondary component appears to
      involve the enteric nervous system and may be cyclic nucleotide dependent. Both
      phases of diarrhea occur in the absence of significant inflammation. Thus age
      dependent rotaviral disease represents an excellent experimental paradigm for
      understanding a noninflammatory diarrhea.

PMID- 11447009
TI  - Receptors and transmission in the brain-gut axis: potential for novel therapies.
      IV. GABA(B) receptors in the brain-gastroesophageal axis.
AB  - GABA(B) receptors are inhibitory G protein-coupled receptors that are commonly
      associated with presynaptic inhibition of transmitter release in the central
      nervous system. In the brain-gastroesophageal axis, a role has recently been
      demonstrated for GABA(B) receptors on extrinsic afferent endings within the
      stomach and esophagus, where they reduce mechanosensitivity. This action is
      compounded by inhibition of communication centrally from these afferents in the
      brain stem and within central circuits. There is a final peripheral action on the
      motor pathway where GABA(B) receptors reduce output of acetylcholine from vagal
      preganglionic motoneurons. These potent, multiple actions of GABA(B) receptors
      may have therapeutic benefit by reducing the triggering of transient lower
      esophageal relaxations, which are the major cause of gastroesophageal reflux. An
      important clinical application is therefore emerging for this recent discovery.

PMID- 11447010
TI  - Bile salt export pump is highly conserved during vertebrate evolution and its
      expression is inhibited by PFIC type II mutations.
AB  - Bile secretion is a fundamental function of the liver of all vertebrates and is
      generated by ATP-dependent transport proteins at the canalicular membrane of
      hepatocytes, particularly by the bile salt export pump BSEP. To determine the
      evolutionary origin and structure-function relationship of this transport
      mechanism, a liver cDNA library from the marine skate Raja erinacea, a 200
      million-year-old vertebrate, was screened for BSEP orthologues. A full-length
      clone was isolated that encodes for 1,348 amino acids and shares 68.5% identity
      to human BSEP. Northern blot analysis revealed a 5-kb transcript only in skate
      liver. Expression of skate Bsep in Sf9 cells demonstrated a sixfold stimulation
      of ATP-dependent taurocholate transport compared with controls, with a Michaelis
      Menten constant of 15 microM, which is comparable to rat Bsep. Sequences at the
      site of published mutations in human BSEP are also conserved in skate Bsep. When
      two of these mutations were introduced into the skate Bsep cDNA, this resulted in
      defective expression of the mutant proteins in Sf9 cells. These studies
      demonstrate that Bsep is a liver-specific ATP-dependent export pump that is
      highly conserved throughout evolution and provide insights into critical
      determinants for the function of this transporter in higher vertebrates.

PMID- 11447011
TI  - Protease-activated receptor-1 stimulates Ca(2+)-dependent Cl(-) secretion in
      human intestinal epithelial cells.
AB  - The thrombin receptor, protease-activated receptor-1 (PAR-1), has wide tissue
      distribution and is involved in many physiological functions. Because thrombin is
      in the intestinal lumen and mucosa during inflammation, we sought to determine
      PAR-1 expression and function in human intestinal epithelial cells. RT-PCR showed
      PAR-1 mRNA expression in SCBN cells, a nontransformed duodenal epithelial cell
      line. Confluent SCBN monolayers mounted in Ussing chambers responded to PAR-1
      activation with a Cl(-)-dependent increase in short-circuit current. The
      secretory effect was blocked by BaCl2 and the Ca(2+)-ATPase inhibitor
      thapsigargin, but not by the L-type Ca(2+) channel blocker verapamil or DIDS, the
      nonselective inhibitor of Ca(2+)-dependent Cl(-) transport. Responses to thrombin
      and PAR-1-activating peptides exhibited auto- and crossdesensitization. Fura 2
      loaded SCBN cells had increased fluorescence after PAR-1 activation, indicating
      increased intracellular Ca(2+). RT-PCR showed that SCBN cells expressed mRNA for
      the cystic fibrosis transmembrane conductance regulator (CFTR) and hypotonicity
      activated Cl(-) channel-2 but not for the Ca(2+)-dependent Cl(-) channel-1. PAR-1
      activation failed to increase intracellular cAMP, suggesting that the CFTR
      channel is not involved in the Cl(-) secretory response. Our data demonstrate
      that PAR-1 is expressed on human intestinal epithelial cells and regulates a
      novel Ca(2+)-dependent Cl(-) secretory pathway. This may be of clinical
      significance in inflammatory intestinal diseases with elevated thrombin levels.

PMID- 11447012
TI  - Nonselective cation channel as a Ca(2+) influx pathway in pepsinogen-secreting
      cells of bullfrog esophagus.
AB  - In pepsinogen-secreting cells of bullfrog (Rana catesbeiana), recent evidence
      suggests that Ca(2+) release from internal stores followed by Ca(2+) influx
      across the plasma membrane elicits pepsinogen secretion. Such a Ca(2+) influx
      could be carried by a background current, potentiated by bombesin, that was found
      in these cells using the whole cell patch-clamp technique. The permeability ratio
      of Cs(+)-Rb(+)-K(+)-Na(+)-Li(+)-N-methyl-D-glucamine(+)-Ca(2+) was
      1.01:1:1:0.86:0.72:0.54:0.34. The current was almost totally blocked by the
      nonselective cation channel blockers La(3+) (0.1 mM) and Gd(3+) (0.1 mM) and was
      activated by intracellular Ca(2+). These properties demonstrated that the
      current, which was activated by bombesin, was a nonselective cation current. At
      the same time, Gd(3+) suppressed pepsinogen secretion by 29 +/- 5.6% in isolated
      pepsinogen-secreting glands. These results are in accord with the idea that a
      nonselective cation channel in pepsinogen-secreting cells plays a role as a
      Ca(2+) influx pathway leading to secretion of pepsinogen in bullfrog esophageal
      mucosa.

PMID- 11447013
TI  - Downregulation of nuclear sex steroid receptor activity correlates with severity
      of alcoholic liver injury.
AB  - Chronic ethanol ingestion in rats and humans results in significant alterations
      in sex steroid levels and expression of sex hormone-dependent phenotype. In this
      study, we used the intragastric feeding model in male rats to determine hepatic
      sex hormone receptor activity under circumstances of chronic ethanol exposure and
      differing degrees of liver injury induced by type of dietary fat. Pathological
      analysis and quantitation of hepatic androgen receptor (AR) and estrogen receptor
      (ER) activity, serum sex hormones, and sex hormone-responsive protein and mRNA
      expression were performed. The activity of the physiologically relevant nuclear
      form of both AR and ER was significantly decreased with ethanol and correlated
      inversely with the severity of liver injury. Serum testosterone levels, as well
      as expression of an androgen-dependent hepatic mRNA, were decreased by ethanol
      and progressive liver injury. Serum estradiol increased with liver injury. We
      postulate that these changes in receptor activity may be due to the oxidative
      stress, reduced cellular energy, and/or altered cytokine milieu known to occur in
      this model.

PMID- 11447014
TI  - H. pylori and transient lower esophageal sphincter relaxations induced by gastric
      distension in healthy humans.
AB  - The role of Helicobacter pylori infection in the control of lower esophageal
      sphincter (LES) motility, especially the occurrence of transient LES relaxations
      (TLESRs), was studied in eight H. pylori-positive and eight H. pylori-negative
      healthy subjects. During endoscopy, biopsy specimens were taken from the cardia,
      fundus, and antrum for determinations of H. pylori status, gastritis, and
      proinflammatory cytokine mucosal concentrations. LES motility was monitored
      during three different 30-min periods: baseline, gastric distension (barostat),
      and gastric distension with CCK infusion. Gastric distension significantly
      increased the TLESR rate, whereas CCK increased the rate of distension-induced
      TLESRs further and reduced resting LES pressure without significant differences
      between infected and noninfected subjects. H. pylori status did not influence
      resting LES pressure or gastric compliance. Cytokine mucosal concentrations were
      increased in infected patients, but no correlation was found with the TLESR rate,
      which was also independent of inflammation at the cardia, fundus, and antrum.
      These results suggest that H. pylori-associated inflammation does not affect the
      motor events involved in the pathogenesis of gastroesophageal reflux.

PMID- 11447015
TI  - Tachykinins mediate slow excitatory postsynaptic transmission in guinea pig
      sphincter of Oddi ganglia.
AB  - Intracellular recording techniques were used to test whether tachykinins could be
      mediators of slow excitatory postsynaptic potentials (EPSPs) in guinea pig
      sphincter of Oddi (SO) ganglia. Application of the tachykinin substance P (SP)
      onto SO neurons caused a prolonged membrane depolarization that was reminiscent
      of the slow EPSP in these cells. Pressure ejection of the neurokinin 3 (NK3)
      receptor-specific agonist senktide caused a similar depolarization; however, no
      responses were detected on application of NK1 or NK2 receptor agonists. The NK3
      receptor antagonist SR-142801 (100 nM) significantly inhibited both SP-induced
      depolarization and the stimulation-evoked slow EPSP, as did NK3 receptor
      desensitization with senktide. Capsaicin, which causes the release of SP from
      small-diameter afferent fibers, induced a depolarization that was similar to the
      evoked slow EPSP in both amplitude and duration. The capsaicin-induced
      depolarization was significantly attenuated in the presence of SR-142801. These
      data indicate that tachykinins, released from extrinsic afferent fibers, act via
      NK3 receptors to provide slow excitatory synaptic input to SO neurons.

PMID- 11447016
TI  - Characterization of a mouse colonic system B(0+) amino acid transporter related
      to amino acid absorption in colon.
AB  - Previous experiments have shown that an amino acid transport system B(0+)
      transporter in cultured colonic epithelial cells mediates amino acid absorption.
      Here we describe the cloning and functional characterization of a system B(0+)
      transporter selectively expressed in the colon. Using the combination of an
      expressed sequence tag database search and RT-PCR approaches, we cloned a mouse
      colonic amino acid transporter, designated mCATB(0+). Northern blot analysis
      revealed that mCATB(0+) was selectively expressed in the large intestine. In situ
      hybridization showed the mCATB(0+) mRNA to be localized in absorptive epithelial
      cells. When expressed in Xenopus oocytes, mCATB(0+) exhibited a Na(+)-dependent
      stereoselective uptake and a broad specificity for neutral and cationic amino
      acids, which is characteristic of amino acid transport system B(0+). In vivo
      [(3)H]glycine uptake assay demonstrated that a system B(0+)-like transporter
      protein was expressed on the apical surface of the colonic absorptive cells. Our
      data suggest that a mouse colonic amino acid transporter mCATB(0+) may absorb
      amino acids from the intestinal contents in the colon.

PMID- 11447017
TI  - Influence of pH on the phase distribution of nascent deoxycholic acid in fresh
      human cecal aspirates.
AB  - Prolonged large bowel transit time and an associated increase in the proportion
      of deoxycholic acid (DCA) in serum and bile have been implicated in the
      development of cholesterol-rich gallstones and colon cancer. Prolongation of
      intestinal transit also increases intracolonic pH that, we hypothesized, should
      favor the solubilization and absorption of newly formed DCA within the colon. To
      test this hypothesis, we performed in vitro studies on homogenized cecal
      aspirates (obtained at colonoscopy) that were incubated anaerobically with
      [14C]cholic acid for 16 h after which the pH was adjusted to between 4.0 and 7.0
      in 0.5-pH unit steps. The resultant reaction mixtures were centrifuged to
      separate the supernatant from the precipitate, and the specific activity of
      [14C]DCA was quantitated in both phases. As the pH in the aspirates was
      manipulated from 4.0 to 7.0, the proportion of newly formed, labeled DCA
      increased in the supernatant and fell in the precipitate, particularly at a
      hydrogen ion concentration of <100 x 10(-7) (equivalent to pH 5.0-7.0). These
      results show that the solubility of DCA in colonic contents increases with
      increasing pH. If solubility is rate limiting, this should lead to increased
      absorption that, in turn, would explain why the proportion of DCA in serum and
      bile increases with the prolongation of large bowel transit time.

PMID- 11447018
TI  - PGE2 triggers recovery of transmucosal resistance via EP receptor cross talk in
      porcine ischemia-injured ileum.
AB  - 16,16-Dimethyl-PGE2 (PGE2) may interact with one of four prostaglandin type E
      (EP) receptors, which signal via cAMP (via EP2 or EP4 receptors) or intracellular
      Ca(2+) (via EP1 receptors). Furthermore, EP3 receptors have several splice
      variants, which may signal via cAMP or intracellular Ca(2+). We sought to
      determine the PGE2 receptor interactions that mediate recovery of transmucosal
      resistance (R) in ischemia-injured porcine ileum. Porcine ileum was subjected to
      45 min of ischemia, after which the mucosa was mounted in Ussing chambers.
      Tissues were pretreated with indomethacin (5 microM). Treatment with the EP1,
      EP2, EP3, and EP4 agonist PGE2 (1 microM) elevated R twofold and significantly
      increased tissue cAMP content, whereas the EP2 and EP4 agonist deoxy-PGE1 (1
      microM) or the EP1 and EP3 agonist sulprostone (1 microM) had no effect. However,
      a combination of deoxy-PGE1 and sulprostone stimulated synergistic elevations in
      R and tissue cAMP content. Furthermore, treatment of tissues with deoxy-PGE1 and
      the Ca(2+) ionophore A-23187 stimulated synergistic increases in R and cAMP,
      indicating that PGE2 triggers recovery of R via EP receptor cross talk mechanisms
      involving cAMP and intracellular Ca(2+).

PMID- 11447019
TI  - Fatty liver vulnerability to endotoxin-induced damage despite NF-kappaB induction
      and inhibited caspase 3 activation.
AB  - Fatty livers are sensitive to lipopolysaccharide (LPS) damage. This study tests
      the hypothesis that this vulnerability occurs because protective, antiapoptotic
      mechanisms are not upregulated appropriately. Genetically obese, leptin-deficient
      ob/ob mice, a model for nonalcoholic fatty liver disease, and their lean litter
      mates were treated with a small dose of LPS. General measures of liver injury,
      early (i.e., cytochrome c release) and late (i.e., activation of caspase 3)
      events that occur during hepatocyte apoptosis, and various aspects of the signal
      transduction pathways that induce nuclear factor-kappaB (NF-kappaB) and several
      of its antiapoptotic transcriptional targets (e.g., inducible nitric oxide
      synthase, bfl-1, and bcl-xL) were compared. Within 0.5-6 h after LPS exposure,
      cytochrome c begins to accumulate in the cytosol of normal livers, and procaspase
      3 cleavage increases. Coincident with these events, kinases (e.g., AKT and Erk-1
      and -2) that result in the degradation of inhibitor kappa-B are activated; NF
      kappaB activity is induced, and NF-kappaB-regulated gene products accumulate.
      Throughout this period, there is negligible histological evidence of liver
      damage, and serum alanine aminotransferase values barely increase over baseline
      values. Although ob/ob livers have significant histological liver injury and 11
      fold greater serum alanine aminotransferase values than those of lean mice by 6 h
      post-LPS, they exhibit greater activation of AKT and Erk, more profound
      reductions in inhibitor kappa-B, enhanced activation of NF-kappaB, and greater
      induction of NF-kappaB-regulated genes. Consistent with this heightened
      antiapoptotic response, increases in cytochrome c and procaspase 3 cleavage
      products are inhibited. Together with evidence that ob/ob hepatocytes have a
      reduced ATP content and undergo increased lysis after in vitro exposure to tumor
      necrosis factor-alpha, these findings suggest that fatty livers are sensitive to
      LPS damage because of vulnerability to necrosis, rather than because of
      apoptosis.

PMID- 11447020
TI  - Impaired biliary lipid secretion in obese Zucker rats: leptin promotes hepatic
      cholesterol clearance.
AB  - Human obesity is associated with elevated plasma leptin levels. Obesity is also
      an important risk factor for cholesterol gallstones, which form as a result of
      cholesterol hypersecretion into bile. Because leptin levels are correlated with
      gallstone prevalence, we explored the effects of acute leptin administration on
      biliary cholesterol secretion using lean (FA/-) and obese (fa/fa) Zucker rats.
      Zucker (fa/fa) rats become obese and hyperleptinemic due to homozygosity for a
      missense mutation in the leptin receptor, which diminishes but does not
      completely eliminate responsiveness to leptin. Rats were infused intravenously
      for 12 h with saline or pharmacological doses of recombinant murine leptin (5
      microg x kg(-1) x min(-1)) sufficient to elevate plasma leptin concentrations to
      500 ng/ml compared with basal levels of 3 and 70 ng/ml in lean and obese rats,
      respectively. Obesity was associated with a marked impairment in biliary
      cholesterol secretion. In biles of obese compared with lean rats, bile salt
      hydrophobicity was decreased whereas phosphatidylcholine hydrophobicity was
      increased. High-dose leptin partially normalized cholesterol secretion in obese
      rats without altering lipid compositions, implying that both chronic effects of
      obesity and relative resistance to leptin contributed to impaired biliary
      cholesterol elimination. In lean rats, acute leptin administration increased
      biliary cholesterol secretion rates. Without affecting hepatic cholesterol
      contents, leptin downregulated hepatic activity of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase, upregulated activities of both sterol 27
      hydroxylase and cholesterol 7alpha-hydroxylase, and lowered plasma very low
      density lipoprotein cholesterol concentrations. Increased biliary cholesterol
      secretion in the setting of decreased cholesterol biosynthesis and increased
      catabolism to bile salts suggests that leptin promotes elimination of plasma
      cholesterol.

PMID- 11447021
TI  - Substrate utilization by intestinal mucosal tissue strips from patients with
      inflammatory bowel disease.
AB  - A primary metabolic disorder may be present in the colonic mucosa of patients
      with ulcerative colitis. Preserving the epithelium in situ, we evaluated the
      metabolism of the colonic mucosa of control patients and patients with ulcerative
      colitis and Crohn's disease. Colonic mucosal strips (approximately 500 mg) were
      incubated with partially 14C-labeled acetate (C2), butyrate (C4), hexanoate (C6),
      octanoate (C8), and glucose, and the production of CO2 and ketone bodies was
      quantitated. Metabolism by small intestinal mucosal strips was also evaluated.
      Compared with controls, no decrease in either CO2 or ketone body production by
      colonic strips from patients with either ulcerative colitis or Crohn's disease
      was observed for any substrate. The CO2 production from each of the C2-C8 fatty
      acids was the same for colonic and small intestinal strips, whereas CO2
      production from glucose was higher in small intestinal strips than in colonic
      strips. The production of ketone bodies was low in small intestinal strips. A
      primary metabolic disorder in the colonic mucosa of patients with inflammatory
      bowel disease was not found.

PMID- 11447022
TI  - Phospholipase C-gamma inhibition prevents EGF protection of intestinal
      cytoskeleton and barrier against oxidants.
AB  - Loss of intestinal barrier integrity is associated with oxidative inflammatory GI
      disorders including inflammatory bowel disease. Using monolayers of human
      intestinal epithelial (Caco-2) cells, we recently reported that epidermal growth
      factor (EGF) protects barrier integrity against oxidants by stabilizing the
      microtubule cytoskeleton, but the mechanism downstream of the EGF receptor (EGFR)
      is not established. We hypothesized that phospholipase C (PLC)-gamma is required.
      Caco-2 monolayers were exposed to oxidant (H2O2) with or without pretreatment
      with EGF or specific inhibitors of EGFR tyrosine kinase (AG-1478, tyrphostin 25)
      or of PLC (L-108, U-73122). Other Caco-2 cells were stably transfected with a
      dominant negative fragment for PLC-gamma (PLCz) to inhibit PLC-gamma activation.
      Doses of EGF that enhanced PLC activity also protected monolayers against oxidant
      induced tubulin disassembly, disruption of the microtubule cytoskeleton, and
      barrier leakiness as assessed by radioimmunoassay, quantitative Western blots,
      high-resolution laser confocal microscopy, and fluorometry, respectively.
      Pretreatment with either type of inhibitor abolished EGF protection. Transfected
      cells also lost EGF protection and showed reduced PLC-gamma phosphorylation and
      activity. We conclude that EGF protection requires PLC-gamma signaling and that
      PLC-gamma may be a useful therapeutic target.

PMID- 11447023
TI  - Transport of protein in the abdominal wall during intraperitoneal therapy. I.
      Theoretical approach.
AB  - Intraperitoneal therapies such as peritoneal dialysis or regional chemotherapy
      use large volumes of solution within the peritoneal cavity. These volumes
      increase intraperitoneal hydrostatic pressure (P(ip)), which causes flow of the
      solution into tissues that surround the cavity. The goal of this paper is to
      integrate new experimental findings in a rigorous mathematical model to predict
      protein transport from the cavity into tissue. The model describes non-steady
      state diffusion and convection of protein through a deformable porous medium with
      simultaneous exchange with the microcirculation and local tissue binding. Model
      parameters are dependent on local tissue pressure, which varies with P(ip).
      Solute interactions with the tissue in terms of local distribution volume (solute
      void space), local binding, and retardation relative to solvent flow are
      demonstrated to be major determinants of tissue concentration profiles and
      protein penetration from the peritoneal cavity. The model predicts the rate of
      fluid loss from the cavity to the abdominal wall in dialysis patients to be 94
      ml/h, within the observed range of 60-100 ml/h. The model is fitted to published
      transport data of IgG, and the retardation coefficient f is estimated to be 0.3,
      which markedly reduces the rate of protein penetration and is far lower than
      previously published estimates. With the value of f = 0.3, model calculations
      predict that P(ip) of 4.4 mmHg and dialysis duration of 24 h result in several
      millimeters of protein penetration into the tissue.

PMID- 11447024
TI  - Cl(-)-dependent secretory mechanisms in isolated rat bile duct epithelial units.
AB  - Cholangiocytes absorb and secrete fluid, modifying primary canalicular bile. In
      several Cl(-)-secreting epithelia, Na(+)-K(+)-2Cl(-) cotransport is a basolateral
      Cl(-) uptake pathway facilitating apical Cl(-) secretion. To determine if
      cholangiocytes possess similar mechanisms independent of CO2/HCO, we assessed Cl(
      )-dependent secretion in rat liver isolated polarized bile duct units (IBDUs) by
      using videomicroscopy. Without CO2/HCO, forskolin (FSK) stimulated secretion
      entirely dependent on Na(+) and Cl(-) and inhibited by Na(+)-K(+)-2Cl(-)
      inhibitor bumetanide. Carbonic anhydrase inhibitor ethoxyzolamide had no effect
      on FSK-stimulated secretion, indicating negligible endogenous CO2/HCO transport.
      In contrast, FSK-stimulated secretion was inhibited approximately 85% by K(+)
      channel inhibitor Ba(2+) and blocked completely by bumetanide plus Ba(2+). IBDU
      Na(+)-K(+)-2Cl(-) cotransport activity was assessed by recording intracellular pH
      during NH4Cl exposure. Bumetanide inhibited initial acidification rates due to NH
      entry in the presence and absence of CO2/HCO. In contrast, when stimulated by
      FSK, a 35% increase in Na(+)-K(+)-2Cl(-) cotransport activity occurred without
      CO2/HCO. These data suggest a cellular model of HCO-independent secretion in
      which Na(+)-K(+)-2Cl(-) cotransport maintains high intracellular Cl(-)
      concentration. Intracellular cAMP concentration increases activate basolateral
      K(+) conductance, raises apical Cl(-) permeability, and causes transcellular Cl(
      ) movement into the lumen. Polarized IBDU cholangiocytes are capable of vectorial
      Cl(-)-dependent fluid secretion independent of HCO. Bumetanide-sensitive Na(+)
      K(+)-2Cl(-) cotransport, Cl(-)/HCO exchange, and Ba(2+)-sensitive K(+) channels
      are important components of stimulated fluid secretion in intrahepatic bile duct
      epithelium.

PMID- 11447025
TI  - Differential expression and regulation of Na(+)/H(+) exchanger isoforms in rabbit
      parietal and mucous cells.
AB  - Several Na(+)/H(+) exchanger (NHE) isoforms are expressed in the stomach, and
      NHE1 and NHE2 knockout mice display gastric mucosal atrophy. This study
      investigated the cellular distribution of the NHE isoforms NHE1, NHE2, NHE3, and
      NHE4 in rabbit gastric epithelial cells and their regulation by intracellular pH
      (pH(i)), hyperosmolarity, and an increase in cAMP. Semiquantitative RT-PCR and
      Northern blot experiments showed high NHE1 and NHE2 mRNA levels in mucous cells
      and high NHE4 mRNA levels in parietal and chief cells. Fluorescence optical
      measurements in cultured rabbit parietal and mucous cells using the pH-sensitive
      dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein and NHE isoform-specific
      inhibitors demonstrated that in both cell types, intracellular acidification
      activates NHE1 and NHE2, whereas hyperosmolarity activates NHE1 and NHE4. The
      relative contribution of the different isoforms to pH(i)- and hyperosmolarity
      activated Na(+)/H(+) exchange in the different cell types paralleled their
      relative expression levels. cAMP elevation also stimulated NHE4, whereas an
      increase in osmolarity above a certain threshold further increased NHE1 and not
      NHE4 activity. We conclude that in rabbit gastric epithelium, NHE1 and NHE4
      regulate cell volume and NHE1 and NHE2 regulate pH(i). The high NHE1 and NHE2
      expression levels in mucous cells may reflect their special need for pH(i)
      regulation during high gastric acidity. NHE4 is likely involved in volume
      regulation during acid secretion.

PMID- 11447026
TI  - Viscoelastic properties of the human colon.
AB  - Our objectives were to characterize colonic viscoelastic properties of the human
      descending colon by assessing pressure-volume (P-V) relationships during
      barostatic balloon distension. In 16 healthy subjects, a balloon was inflated to
      44 mmHg and then deflated to 0 mmHg in 4-mmHg steps at 10, 30, and 60 ml/min,
      allowing volume fluctuations to stabilize at each pressure increment. Thereafter,
      these "quasi-static" P-V curves were compared with "dynamic" distensions to 300
      ml, at 1 and 10 ml/s, before and after intravenous atropine in another five
      subjects. During quasi-static curves, balloon volume stabilized at each pressure
      increment. Quasi-static P-V curves were reproducible within individuals and
      approximated to a power exponential function and revealed hysteresis, indicative
      of viscoelasticity. Body mass index influenced quasi-static P-V curves during
      inflation but not during deflation. The colon was less compliant during dynamic
      distensions at 10 ml/s than during quasi-static distensions. Atropine increased
      quasi-static compliance and attenuated differences between quasi-static and rapid
      distensions. We conclude that colonic viscoelastic properties can be assessed by
      quasi-static P-V curves. Rapid colonic distension activated neural reflexes,
      thereby reducing colonic compliance compared with quasi-static distensions.

PMID- 11447027
TI  - Myosin light chain kinase- and PKC-dependent contraction of LES and esophageal
      smooth muscle.
AB  - In smooth muscle cells enzymatically isolated from circular muscle of the
      esophagus (ESO) and lower esophageal sphincter (LES), ACh-induced contraction and
      myosin light chain (MLC) phosphorylation were similar. Contraction and
      phosphorylation induced by purified MLC kinase (MLCK) were significantly greater
      in LES than ESO. ACh-induced contraction and MLC phosphorylation were inhibited
      by calmodulin and MLCK inhibitors in LES and by protein kinase C (PKC) inhibitors
      in ESO. Contraction of LES and ESO induced by the PKC agonist 1,2
      dioctanoylglycerol (DG) was unaffected by MLCK inhibitors. Caldesmon and calponin
      concentration-dependently inhibited ACh-induced contraction of ESO and not LES.
      In ESO, caldesmon antagonist GS17C reversed caldesmon- but not calponin-induced
      ACh inhibition. GS17C caused contraction of permeabilized ESO but had much less
      effect on LES. GS17C-induced contraction was not affected by MLCK inhibitors,
      suggesting that MLCK may not regulate caldesmon-mediated contraction. DG-induced
      contraction of ESO and LES was inhibited by caldesmon and calponinin, suggesting
      that these proteins may regulate PKC-dependent contraction. We conclude that
      calmodulin and MLCK play a role in ACh-induced LES contraction, whereas the
      classical MLCK may not be the major kinase responsible for contraction and
      phosphorylation of MLC in ESO. ESO contraction is PKC dependent. Caldesmon and/or
      calponin may play a role in PKC-dependent contraction.

PMID- 11447028
TI  - Interrelationship between colonic muscularis mucosae activity and changes in
      transmucosal potential difference.
AB  - This in vitro study investigated the relationship between rabbit colonic
      muscularis mucosae motor activity and changes in transmucosal potential
      difference. Spontaneous muscle contractions and potential difference oscillations
      occurred independently and were not neurally driven. ACh and histamine directly
      stimulated the muscularis mucosae, but their mucosal effects were largely
      indirect, suggesting that muscularis mucosae contractions promote epithelial
      secretion. 1,1-Dimethyl-4-phenyl-piperazinium iodide and vasoactive intestinal
      polypeptide induced large potential difference changes but small muscularis
      mucosae contractions, demonstrating mucosal secretion without significant muscle
      activity. Lowered intraluminal pH directly stimulated the muscle, whereas a bile
      salt-lipid mixture evoked TTX- and atropine-sensitive increases in its
      contractile activity. Increased intraluminal pressure and hypertonic luminal
      perfusion did not elicit muscularis mucosae excitation. Thus under basal
      conditions muscle and mucosal activities are independent, but evoked muscularis
      mucosae contractions can stimulate epithelial secretion. In response to specific
      luminal stimuli, muscularis mucosae motor activity is increased via the
      activation of cholinergic nerves. These data suggest that muscularis mucosae and
      mucosal functions are physiologically linked and that their activities can be
      coordinated by multiple mechanisms.

PMID- 11447029
TI  - Abnormalities of gallbladder muscle associated with acute inflammation in guinea
      pigs.
AB  - Muscle strips from experimental acute cholecystitis (AC) exhibit a defective
      contraction. The mechanisms responsible for this impaired contraction are not
      known. The present studies investigated the nature of these abnormalities. AC was
      induced by ligating the common bile duct of guinea pigs for 3 days. Contraction
      was studied in enzymatic dissociated muscle cells. Cholecystokinin (CCK) and
      prostaglandin E2 (PGE2) receptor binding studies were performed by radioreceptor
      assay. The levels of lipid peroxidation, cholesterol, phospholipid, and H2O2 as
      well as the catalase and superoxide dismutase (SOD) activities were determined.
      PGE2 content was measured by radioimmunoassay. Muscle contraction induced by CCK,
      ACh, or KCl was significantly reduced in AC, but PGE2-induced contraction
      remained normal. GTPgammaS, diacyglycerol (DAG), and 1,4,5-trisphosphate (IP3),
      which bypass the plasma membrane, caused a normal contraction in AC. The number
      of functional receptors for CCK was significantly decreased, whereas those for
      PGE2 remained unchanged in AC. There was a reduction in the phospholipid content
      and increase in the level of lipid peroxidation as well as H2O2 content in the
      plasma membrane in AC. The PGE2 content and the activities of catalase and SOD
      were also elevated. These data suggest that AC cause damage to the constituents
      of the plasma membrane of muscle cells. The preservation of the PGE2 receptors
      may be the result of muscle cytoprotection.

PMID- 11447030
TI  - Activation of poly(ADP-ribose) polymerase in severe hemorrhagic shock and
      resuscitation.
AB  - This study examines activation of poly(ADP-ribose) polymerase (PARP) in the ileum
      during hemorrhage and resuscitation and determines if inhibition of PARP reduces
      organ dysfunction and metabolic acidosis. Awake, nonheparinized rats were
      hemorrhaged (40 mmHg, 60 min). Resuscitation used Ringer's solution (2 1/3 x shed
      volume) and packed red blood cells (2/3 shed volume). Ileal PARP activity was
      elevated at the end of hemorrhage (3.6-fold) and 10 min of resuscitation (5
      fold). The subsequent decline in PARP activity observed after 60 min of
      resuscitation was not due to cleavage by caspase-3. Ileum permeability increased
      10-fold and circulating liver enzymes increased 4- to 6-fold following 60 min of
      resuscitation in animals pretreated with 3-aminobenzoic acid, a structural analog
      that does not inhibit PARP. Pretreatment with 3-aminobenzamide (3-AB), a PARP
      inhibitor, reduced these changes, whereas posttreatment with a bolus of 3-AB was
      ineffective. Metabolic acidosis, accumulation of lactate, and base deficit was
      reduced by pretreatment with 3-AB. PARP is activated in the ileum by hemorrhage
      and by resuscitation. Activation of PARP contributes to organ dysfunction in the
      ileum and liver and appears to be central to the development of metabolic
      acidosis.

PMID- 11447031
TI  - Molecular characterization and organ distribution of type A and B cholecystokinin
      receptors in cynomolgus monkey.
AB  - Differences in the molecular structure or organ distribution of receptors can
      limit the usefulness of a given species for drug studies. In this work, we have
      studied cholecystokinin (CCK) receptors in cynomolgus monkey, an animal model
      useful for preclinical testing. The type A CCK receptor cDNA was cloned and
      predicted to encode a 428 amino acid peptide that was 98% identical to the human
      receptor. Only 2 of the 10 residues that were distinct from the human receptor
      were not present in other cloned CCK receptor species. A Chinese hamster ovary
      cell line that stably expressed this receptor was developed. The cynomolgus
      receptor expressed in this environment was functionally indistinguishable from
      the human receptor, binding CCK with high affinity [inhibition constant (K(I)) =
      1.8 +/- 0.5 nM] and exhibiting a potent intracellular calcium signaling response
      to this hormone (EC(50) = 6.6 +/- 2.1 pM). Like the human type A CCK receptor,
      this receptor was expressed prominently in monkey gallbladder and stomach and was
      expressed in low levels in brain and pancreas. The type B CCK receptor cDNA was
      cloned from stomach and brain (450 residue receptor that is 96% identical to the
      human receptor), where it was highly expressed yet was undetectable in
      gallbladder or pancreas. This work confirms the relevance of the cynomolgus
      species for preclinical testing of drugs acting on the type A CCK receptor.

PMID- 11447032
TI  - Contribution of ion pair complexation with bile salts to biliary excretion of
      organic cations in rats.
AB  - The objective of this study was to examine whether ion pair complexation with
      endogenous bile salts in hepatocytes contributes to the preferential biliary
      excretion of organic cations (OCs). Tributylmethylammonium (TBuMA; mol wt 200)
      and triethylmethylammonium (TEMA; mol wt 116) were selected as model OCs that
      exhibit significant and negligible biliary excretion, respectively, in rats. The
      apparent lipophilicity of TBuMA, but not that of TEMA, was increased by the
      presence of either rat bile or specific bile salts, suggesting the formation of
      lipophilic ion pair complexes for TBuMA with bile salts in the liver. The uptake
      of TBuMA into canalicular liver plasma membrane (cLPM) vesicles, but not that of
      TEMA, was increased in the presence of bile salts, with a significant increase
      for both ATP-dependent transport and passive diffusion. The uptake of TBuMA in
      the presence of the bile salts was inhibited by representative P-glycoprotein (P
      gp) substrates and vice versa, suggesting the involvement of P-gp in the
      canalicular excretion of TBuMA-bile salt complexes in vivo. Increased affinity
      toward P-gp is suggested as the mechanism responsible for the increased ATP
      dependent transport for the ion pair complexes. We propose that ion pair
      formation with bile slats in hepatocytes may be responsible for the preferential
      biliary excretion of high-molecular-weight OCs including TBuMA.

PMID- 11447033
TI  - Pancreatic phospholipase A2 from the small intestine is a secretin-releasing
      factor in rats.
AB  - A secretin-releasing activity exists in the upper small intestine and pancreatic
      juice in the rat and the dog. Group I pancreatic phospholipase A2 (PLA2) in
      canine pancreatic juice and porcine pancreatic PLA2 stimulate the release of
      secretin from both STC-1 cells and a secretin-producing cell (S cell)-enriched
      preparation isolated from rat duodenal mucosa. We investigated the distribution
      and release of pancreatic PLA2-like immunoreactivity in the gastrointestinal
      tract and the role of PLA2 on the release of secretin and pancreatic exocrine
      secretion in response to duodenal acidification in anesthetized rats. PLA2-like
      immunoreactivity was detected in the mucosa throughout the gastrointestinal
      tract. High concentrations of PLA2 were found in both the small intestine and the
      pancreas. Duodenal acidification significantly increased the release of PLA2 from
      the upper small intestine (385% over basal secretion). Intravenous infusion of an
      anti-PLA2 serum (anti-PLA2) dose-dependently inhibited the release of secretin
      and pancreatic exocrine secretion in response to duodenal acid perfusion.
      Preincubation of the concentrate of intestinal acid perfusate (10-fold) from
      donor rats with the anti-PLA2 significantly suppressed its stimulation of
      secretin release and pancreatic exocrine secretion in recipient rats. We conclude
      that pancreatic PLA2 also functions as a secretin-releasing factor in the small
      intestine that mediates acid-stimulated release of secretin in rats.

PMID- 11447034
TI  - Gap junctions in gastrointestinal muscle contain multiple connexins.
AB  - In the canine gastrointestinal tract, the roles that gap junctions play in
      pacemaking and neurotransmission are unclear. Using antibodies to connexin
      (Cx)43, Cx45, and Cx40, we determined the distribution of these connexins. Cx43
      was present in all locations where structural gap junctions occur. Cx40 was also
      widely distributed in the circular muscle of the lower esophageal sphincter
      (LES), stomach, and ileum. Cx45 was sparsely distributed in circular muscle of
      the LES. In the interstitial cells of Cajal (ICC) networks of myenteric plexus,
      in the deep muscular and submuscular plexuses, sparse Cx45 and Cx40
      immunoreactivity was present. In colon, immunoreactivity was found only in the
      myenteric and submuscular plexus and nearby circular muscle cells. No
      immunoreactivity was found in sites lacking structural gap junctions
      (longitudinal muscle, inner circular muscle of the intestine, and most circular
      muscle of the colon). Studies of colocalization of connexins suggested that in
      the ICC networks, some colocalization of Cx43 with Cx40 and/or Cx45 occurred.
      Thus gap junctions in canine intestine may be heterotypic or heteromeric and have
      different conductance properties in different regions based on different connexin
      compositions.

PMID- 11447035
TI  - Deletion of neutral endopeptidase exacerbates intestinal inflammation induced by
      Clostridium difficile toxin A.
AB  - Toxin A (TxA) of Clostridium difficile induces acute inflammation of the
      intestine initiated by release of substance P (SP) and activation of the
      neurokinin-1 receptor. However, the mechanisms that terminate this response are
      unknown. We determined whether the SP-degrading enzyme neutral endopeptidase
      (NEP, EC 3.4.24.11) terminates TxA-induced enteritis. We used both genetic
      deletion and pharmacological inhibition of NEP to test this hypothesis. In wild
      type mice, instillation of TxA (0.5-5 microg) into ileal loops for 3 h dose
      dependently increased ileal fluid secretion, stimulated granulocyte
      transmigration determined by myeloperoxidase activity, and caused histological
      damage characterized by depletion of enterocytes, edema, and neutrophil
      accumulation. Deletion of NEP reduced the threshold secretory and inflammatory
      dose of TxA and exacerbated the inflammatory responses by more than twofold. This
      exacerbated inflammation was prevented by pretreatment with recombinant NEP.
      Conversely, pretreatment of wild-type mice with the NEP inhibitor phosphoramidon
      exacerbated enteritis. Thus NEP terminates enteritis induced by C. difficile TxA,
      underlying the importance of SP degradation in limiting neurogenic inflammation.

PMID- 11447036
TI  - Developmental variability in expression and regulation of inducible nitric oxide
      synthase in rat intestine.
AB  - Inducible nitric oxide synthase (iNOS) may be a key mediator of intestinal
      injury, which varies with developmental age. One member of the mitogen-activated
      protein kinase (MAPK) family, p38, is involved in the lipopolysaccharide (LPS)
      mediated iNOS induction. The involvement of p38 MAPK in basal and LPS-induced
      iNOS expression was examined in the rat intestine at two developmental ages.
      Neonatal (4 days postnatal) and adolescent (15 days postnatal) rats were injected
      with LPS (5 microg/g ip), a selective p38 inhibitor (SB 203580), or both. Tissue
      was removed after 4 h and 6 h for mRNA and protein analysis. iNOS mRNA and
      protein were markedly upregulated in the adolescent female following LPS
      exposure, whereas males had an attenuated response. Neonates had a minimal
      response. SB 203580 suppressed LPS-induced iNOS mRNA and protein in the ileum,
      more so in females than in males. Adolescent ileal p38 activation was
      constitutively high and nonresponsive to LPS. Basal and post-LPS p38
      phosphorylation was low in neonatal ileum. We conclude that ileal iNOS expression
      is developmentally regulated and influenced by gender and that p38 is permissive
      for LPS effect. The developmental regulation of p38 may contribute to age
      dependent variations of intestinal injury.

PMID- 11447037
TI  - Acute cold exposure induces vagally mediated Fos expression in gastric myenteric
      neurons in conscious rats.
AB  - Acute cold exposure-induced activation of gastric myenteric neurons in conscious
      rats was examined on longitudinal muscle-myenteric plexus whole mount
      preparations. Few Fos-immunoreactive (IR) cells (<1/ganglion) were observed in 24
      h fasted rats semirestrained at room temperature. Cold exposure (4 degrees C) for
      1-3 h induced a time-related increase of Fos-IR cells in corpus and antral
      myenteric ganglia with a maximal plateau response (17 +/- 3 and 18 +/- 3
      cells/ganglion, respectively) occurring at 2 h. Gastric vagotomy partly
      prevented, whereas bilateral cervical vagotomy completely abolished, Fos
      expression in the myenteric cells induced by cold exposure (2 h). Hexamethonium
      (20 mg/kg) also prevented 3-h cold exposure-induced myenteric Fos expression by
      76-80%, whereas atropine or bretylium had no effect. Double labeling revealed
      that cold (3 h)-induced Fos-IR myenteric cells were mainly neurons, including a
      substantial number of choline acetyltransferase-containing neurons and most NADPH
      diaphorase-positive neurons. These results indicate that acute cold exposure
      activates cholinergic as well as nitrergic neurons in the gastric myenteric
      ganglia through vagal nicotinic pathways in conscious rats.

PMID- 11447038
TI  - Enteral feeding decreases gut apoptosis, permeability, and lung inflammation
      during murine endotoxemia.
AB  - We tested the hypothesis that endotoxemia and fasting are associated with
      increased gut apoptotic activity, gut permeability, and inflammation in a distant
      organ. Fed or fasted CD-1 mice were studied 6 h after intraperitoneal injection
      of either saline (sham) or endotoxin (4 mg/kg of 0111:B4 Escherichia coli
      lipopolysaccharide). We found that endotoxin increased gut caspase-3 and -6
      activity by 4.9 +/- 0.6- and 4.5 +/- 0.5-fold, respectively (P < 0.001), and
      increased terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling
      (TUNEL) staining of mucosal cells (P < 0.05). Feeding decreased caspase-3
      activity by 40% (P < 0.05) and decreased endotoxin-induced TUNEL staining (P <
      0.05). Endotoxin increased gut poly(ADP-ribose) polymerase activity by 15% (P <
      0.05). Endotoxin increased gut permeability by 44% (P < 0.05), an effect reduced
      36% by feeding (P < 0.05). Similarly, endotoxin increased pulmonary neutrophil
      infiltration (6.0 +/- 1.0-fold, P < 0.001) and increased lung interleukin (IL)-6
      (5.9 +/- 0.1-fold, P < 0.001) and macrophage inflammatory protein (MIP)-2
      expression (290 +/- 40-fold, P < 0.001), whereas feeding decreased this effect by
      43% for neutrophils, 40% for IL-6 (P < 0.05), and 35% for MIP-2 (P < 0.05). Thus
      endotoxin increases gut apoptotic activity, gut permeability, and pulmonary
      inflammation. Enteral feeding may decrease the distant organ inflammation by
      reducing gut apoptosis, thereby maintaining gut mucosal function during
      endotoxemia.

PMID- 11447039
TI  - Mac-1 (CD11b/CD18) and intercellular adhesion molecule-1 in ischemia-reperfusion
      injury of rat liver.
AB  - The chronological expression (over 24 h) of two adhesion molecules [intercellular
      adhesion molecule-1 (ICAM-1) and CD11b/CD18 (Mac-1)] and the extent of liver
      damage, including injury to sinusoidal endothelial cells (SECs) and hepatocyte
      apoptosis, were investigated under two conditions of rat liver ischemia
      reperfusion (I/R) injury: reversible (30 min) and fatal I/R (60 min). The
      chronological profiles of upregulation of ICAM-1 on hepatocytes and Mac-1 showed
      changes in parallel with the other liver damage parameters, and the extent of
      upregulation and various parameters of liver injury were more advanced in the 60
      min I/R group. Paradoxically, the degree of ICAM-1 upregulation of SECs decreased
      significantly in the 60-min I/R group vs. the 30-min I/R group. Repression of
      hepatocyte apoptosis by administration of the caspase inhibitor ZVAD-fmk resulted
      in attenuation of neutrophil infiltration and liver injury. These findings
      indicate that 1) neutrophil infiltration is involved in the development of liver
      I/R injury; 2) interaction between ICAM-1 on SECs and Mac-1 on neutrophils is not
      an essential step for neutrophil transmigration through the endothelial layer
      because SECs, specifically, were impaired in the early stages of liver I/R
      injury; 3) the role of ICAM-1 and Mac-1 is to adhere neutrophils firmly to
      hepatocytes and activate neutrophils; and 4) excessive parenchymal apoptosis may
      be the signal for the neutrophil-induced inflammatory and necrotic reaction.

PMID- 11447040
TI  - Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced
      colitis in rats.
AB  - Preliminary studies showed that the inducible form of heme oxygenase (HO-1) was
      induced and played a protective role in the process of inflammation. The present
      study investigated the possible role of HO-1 in 2,4,6-trinitrobenzene sulfonic
      acid (TNBS)-induced colitis in rats. We measured HO-1 activity in TNBS-induced
      colitis in rats and analyzed the severity of colitis along with altered HO
      activity by assessing lesion area and myeloperoxidase activity. HO-1 mRNA and
      protein expressions were determined at different time points after TNBS
      induction. Free radical production and inducible nitric oxide synthase (iNOS),
      which participate in oxidative injury, were also assayed. HO activity and HO-1
      gene expression increased markedly after TNBS induction. Administration with tin
      mesoporphyrin (SnMP), a HO inhibitor, potentiated the colonic damage along with a
      reduction in HO-1 activity. Furthermore, the reduction of HO-1 expression by SnMP
      also enhanced reactive oxygen species and iNOS expression, both of which were
      dramatically increased after the TNBS enema. L-Arginine pretreatment further
      aggravated the injurious action of SnMP. Our results indicate that HO-1 plays a
      protective role in the colonic damage induced by the TNBS enema, and the
      preventive effects probably result from decreased free radical production and
      inhibition of iNOS expression in colonic tissues.

PMID- 11447041
TI  - GSTM1, GSTT1, and the risk of squamous cell carcinoma of the head and neck: a
      mini-HuGE review.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is a group of cancers of
      epithelial origin that may provide an ideal model for the study of gene
      environment interaction. SCCHN includes squamous cell carcinomas of the oral
      cavity, pharynx, and larynx. Approximately 90% of the attributable risk for oral
      cancer and 80% of the attributable risk for larynx cancer results from tobacco
      use. Tobacco smoking has been demonstrated to increase the risk of SCCHN in a
      dose-response fashion. Polymorphisms of carcinogen-metabolizing enzymes, known to
      be involved in metabolism of carcinogens found in tobacco smoke, are relatively
      common in most populations. This paper provides a concise review of the 24
      published studies that evaluated the risk of SCCHN in relation to two deletion
      polymorphisms of the glutathione S-transferase family: GSTM1 and GSTT1. Patterns
      of risk based on the site of the tumor and on nationality are presented, as are
      some methodological weaknesses of the studies. The results of these studies are
      inconsistent, with some reporting weak-to-moderate associations and others
      finding no elevation in risk for the main effect of the gene. Few studies have
      directly evaluated the interaction with tobacco. Well-designed, population-based
      studies of adequate size are needed.

PMID- 11447042
TI  - Parental occupational exposures to chemicals and incidence of neuroblastoma in
      offspring.
AB  - To evaluate the effects of parental occupational chemical exposures on incidence
      of neuroblastoma in offspring, the authors conducted a multicenter case-control
      study, using detailed exposure information that allowed examination of specific
      chemicals. Cases were 538 children aged 19 years who were newly diagnosed with
      confirmed neuroblastoma in 1992-1994 and were registered at any of 139
      participating hospitals in the United States and Canada. One age-matched control
      for each of 504 cases was selected through random digit dialing. Self-reported
      exposures were reviewed by an industrial hygienist, and improbable exposures were
      reclassified. Effect estimates were calculated using unconditional logistic
      regression, adjusting for child's age and maternal demographic factors. Maternal
      exposures to most chemicals were not associated with neuroblastoma. Paternal
      exposures to hydrocarbons such as diesel fuel (odds ratio (OR) = 1.5; 95%
      confidence interval (CI): 0.8, 2.6), lacquer thinner (OR = 3.5; 95% CI: 1.6,
      7.8), and turpentine (OR = 10.4; 95% CI: 2.4, 44.8) were associated with an
      increased incidence of neuroblastoma, as were exposures to wood dust (OR = 1.5;
      95% CI: 0.8, 2.8) and solders (OR = 2.6; 95% CI: 0.9, 7.1). The detailed exposure
      information available in this study has provided additional clues about the role
      of parental occupation as a risk factor for neuroblastoma.

PMID- 11447043
TI  - Relation between breastfeeding and the prevalence of asthma : the Tokorozawa
      Childhood Asthma and Pollinosis Study.
AB  - Many risk factors for asthma have been proposed including age, gender (male),
      smoking, and family history of asthma. The importance of breastfeeding to
      childhood asthma is a controversial issue. The present study investigated the
      relation between breastfeeding and the prevalence of asthma among a childhood
      population. The subjects were 25,767 students, representing all public elementary
      and junior high schools in Tokorozawa, Japan (age range, 6--15 years). The study
      population included 2,315 students with asthma and 21,513 controls. Participants'
      parents completed the Japanese version of the American Thoracic Society and
      Division of Lung Diseases, National Heart, Lung, and Blood Institute,
      questionnaire for children adopted by the Japanese Environmental Agency in 1998.
      The authors added supplementary questions on the parental history of asthma and
      feeding patterns from the age of 0--3 months. The risk of breastfeeding for
      asthma was compared with that of artificial feeding. After adjustment for age,
      gender, parental smoking status, and parental history of asthma, a significantly
      higher prevalence of asthma was noted among children who had been breastfed
      (adjusted odds ratio = 1.198; 95% confidence interval: 1.054, 1.363; p for trend
      < 0.01). The results indicated that breastfeeding in infancy might be related to
      the higher prevalence of asthma during preadolescence.

PMID- 11447044
TI  - Is suicide contagious? A study of the relation between exposure to the suicidal
      behavior of others and nearly lethal suicide attempts.
AB  - This study sought to determine the association between nearly lethal suicide
      attempts and exposure to the suicidal behavior of parents, relatives, friends, or
      acquaintances and to accounts of suicide in the media. The authors conducted a
      population-based case-control study in Houston, Texas, from November 1992 through
      July 1995. They interviewed 153 victims of attempted suicide aged 13--34 years
      who had been treated at emergency departments in Houston and a random sample of
      513 control subjects. After controlling for potentially confounding variables,
      the authors found that exposure to the suicidal behavior of a parent (adjusted OR
      = 1.5; 95% CI: 0.6, 3.6; p = 0.42) or a nonparent relative (adjusted OR = 1.2;
      95% CI: 0.7, 2.0; p = 0.55) was not significantly associated with nearly lethal
      suicide attempts. Both exposure to the suicidal behavior of a friend or
      acquaintance (adjusted OR = 0.6; 95% CI: 0.4, 1.0; p = 0.05) and exposure to
      accounts of suicidal behavior in the media (adjusted OR = 0.2; 95% CI: 0.1, 0.3;
      p = 0.00) were associated with a lower risk of nearly lethal suicide attempts.
      Exposure to accounts of suicidal behavior in the media and, to a lesser extent,
      exposure to the suicidal behavior of friends or acquaintances may be protective
      for nearly lethal suicide attempts, but further research is needed to better
      understand the mechanisms underlying these findings.

PMID- 11447045
TI  - Variations in the impact of long-term wartime stressors on mortality among the
      middle-aged and older population in Beirut, Lebanon, 1983--1993.
AB  - The authors investigated the relation between exposure to wartime events and
      cardiovascular disease (CVD) and all-cause mortality in Lebanon, which recently
      underwent a 16-year civil war. The study population comprised a representative
      cohort (n = 1,786) of middle-aged and older men and women who, in 1983,
      participated in a community-based health interview survey. In 1993, the authors
      traced 87.7 % of the original cohort (n = 1,567) and assessed their vital status,
      exposure to war-related events, and, in case they had died, cause of death. War
      experiences were aggregated into different clusters according to type of
      exposure, realm affected (human vs. property losses), and person central to the
      event. Women, but not men, had a significantly elevated CVD mortality risk for
      exposures to human traumas that occurred to them (rate ratio = 3.37, 95%
      confidence interval: 1.41, 8.05) or their families (rate ratio = 1.45, 95%
      confidence interval: 1.20, 1.74). Exposure to property losses and work-related
      problems carried a greater mortality risk for men, particularly those with lower
      levels of education, than for women. Subjects displaced during the war had a
      significantly higher risk for CVD and total mortality. These results suggest
      that, during prolonged wars, different elements of exposures have a long-term
      impact on mortality, with effects varying by gender and socioeconomic resources.

PMID- 11447046
TI  - Is open-angle glaucoma associated with early menopause? The Rotterdam Study.
AB  - The authors examined the association between age at menopause and open-angle
      glaucoma among women aged > or = 55 years in the population-based Rotterdam Study
      (1990--1993). Information on age and type of menopause was obtained by interview.
      Subjects (n = 3,078) were stratified into three categories according to age at
      menopause: <45 years, 45--49 years, and > or = 50 years, with the last group
      serving as the reference group. Diagnosis of open-angle glaucoma was based on the
      presence of a glaucomatous visual field defect and glaucomatous optic neuropathy.
      Open-angle glaucoma was diagnosed in 78 women with a natural menopause and 15
      women with an artificial menopause. In the category of natural menopause, women
      who went through menopause before reaching the age of 45 years had a higher risk
      of open-angle glaucoma than the reference group (odds ratio = 2.6; 95% confidence
      interval: 1.5, 4.8), after adjustment for age and use of hormone replacement
      therapy. Among women who went through menopause between the ages of 45 and 49
      years, the odds ratio was 1.1 (95% confidence interval: 0.7, 2.0). These findings
      suggest that early menopause is associated with a higher risk of open-angle
      glaucoma.

PMID- 11447047
TI  - Dietary antioxidants and peripheral arterial disease : the Rotterdam Study.
AB  - This study examined cross-sectionally the association of dietary beta-carotene,
      vitamin C, and vitamin E with peripheral arterial disease in Rotterdam, the
      Netherlands (1990--1993). The 4,367 subjects from the Rotterdam Study were aged
      55--94 years and had no previous cardiovascular disease at baseline. Diet was
      assessed with a food frequency questionnaire. Peripheral arterial disease was
      defined as an ankle-arm systolic blood pressure index (AAI) of < or = 0.9 and was
      present in 204 men and 370 women. In multivariate-adjusted logistic regression
      analyses, vitamin C intake was significantly inversely associated with peripheral
      arterial disease in women (highest vs. lowest quartile: relative risk = 0.64, 95%
      confidence interval (CI): 0.48, 0.89; p(trend) = 0.006), and a 100-mg increase in
      intake was associated with a 0.013 AAI increase (95% CI: 0.001, 0.025). In men,
      vitamin E intake was inversely associated with peripheral arterial disease
      (relative risk = 0.67, 95% CI: 0.44, 1.03; p(trend) = 0.067); a 10-mg increase in
      intake was associated with a 0.015 AAI increase (95% CI: 0.001, 0.031). Whether
      these differences in antioxidant intake and the risk of a low AAI and of
      peripheral arterial disease between sexes are attributable to a different food
      pattern for men compared with women remains to be elucidated.

PMID- 11447048
TI  - Lifestyle factors and plasma homocysteine concentrations in a general population
      sample.
AB  - The authors cross-sectionally investigated the extent to which coffee, tea, and
      alcohol consumption, physical activity, and smoking were associated with
      nonfasting total plasma homocysteine concentrations in a random sample of 3,025
      Dutch adults aged 20--65 years from a population-based cohort examined in 1993-
      1996 (n = 19,066). The lifestyle factors most strongly associated with plasma
      total homocysteine level were smoking (positive), alcohol drinking (negative),
      and coffee consumption (positive). The smoking effect was most prominent in
      women, and the alcohol effect was most pronounced in men. Data indicated that
      independently of other lifestyle factors, age, and intake of folate and B vitamin
      supplements, a change in lifestyle could result in a 0.1- to 1.7-micromol/liter
      change in plasma total homocysteine level. The authors conclude that lifestyle
      changes could result in a public-health-relevant change in plasma total
      homocysteine concentrations.

PMID- 11447049
TI  - Influenza vaccine effectiveness among elderly nursing home residents: a cohort
      study.
AB  - Outbreaks of influenza in nursing homes still occur, even when a large portion of
      residents have been inoculated with inactivated vaccine. Data were collected in
      1991--1992 from 83 eligible skilled nursing homes located in southern Lower
      Michigan to determine the effectiveness of inactivated influenza vaccine in
      preventing influenza-like illness and influenza-associated pneumonia.
      Surveillance was conducted to identify the occurrence of influenza in the homes
      and, at the end of the season, specific data were gathered on all residents of
      homes with influenza activity. Age- and sex-adjusted estimates of vaccine
      effectiveness were calculated using Cox proportional hazards models for each
      nursing home. Estimates were pooled using precision-based weights calculated from
      data for each home. Vaccine was found to be 33% effective in preventing total
      respiratory illness (influenza-like illness and clinically diagnosed pneumonia).
      In prevention of pneumonia alone, vaccine was 43% effective. The estimate for
      prevention of pneumonia rose to 55% if the period under consideration was limited
      to the time of peak influenza activity. Given the number of eligible homes and
      the cohort methodology used, the results support continuation of current policy,
      encouraging use of vaccine in all nursing home residents.

PMID- 11447050
TI  - Prevalence of antibodies to four herpesviruses among adults with glioma and
      controls.
AB  - The authors previously reported statistically significant inverse associations
      between adult onset glioma and histories of chickenpox and shingles among 462
      cases and 443 controls in the San Francisco Bay Area Adult Glioma Study (1991-
      1995) and a suggestive but nonsignificant inverse association with immunoglobulin
      G antibodies to varicella-zoster virus in a small subset of these cases. This
      report considers antibodies to four common herpesviruses (varicella zoster,
      herpes simplex, cytomegalovirus, and Epstein Barr) among 134 cases and 165
      controls that represent all subjects for whom usable blood specimens were
      available. The prevalences of immunoglobulin G antibodies to varicella-zoster
      virus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were 90%,
      71%, 57%, and 90%, respectively. After adjustment for age, White versus non-White
      ethnicity, and gender, glioblastoma cases were less likely than controls to have
      immunoglobulin G antibodies to varicella-zoster virus (odds ratio = 0.4; 95%
      confidence interval: 0.1, 0.9). They were also somewhat less likely to have
      antibodies to Epstein-Barr virus but somewhat more likely to have antibodies to
      herpes simplex virus and cytomegalovirus. Antibody prevalences to all four
      herpesviruses were similar between cases with other glioma histologies and
      controls. These results corroborate our previously suggestive findings of an
      inverse association of varicella-zoster virus antibodies with adult onset glioma.

PMID- 11447051
TI  - Pathogenicity and convalescent excretion of Campylobacter in rural Egyptian
      children.
AB  - Campylobacter infection in developing countries has not received much public
      health attention because of the observation that infections are not associated
      with disease beyond the first 6 months of life. A cohort of 397 Egyptian children
      aged less than 3 years, who were observed twice weekly during 1995--1998,
      experienced an incidence of 0.6 episodes of Campylobacter diarrhea per child
      year. A total of 13% of the Campylobacter diarrheal episodes were characterized
      by severe dehydration. Age-specific incidence rates (episodes per year) were 0.9
      in infants aged less than 6 months, 1.5 in those 6--12 months, and 0.4 and 0.2 in
      the second and third years of life, respectively. Convalescent excretion of
      Campylobacter after a diarrheal episode might be enhancing transmission and
      contributing to this high incidence. Observed risk factors for Campylobacter
      diarrhea were poor hygienic conditions and the presence of animals in the house.
      Regardless of the child's age, a first infection by Campylobacter was associated
      with diarrhea (odds ratio = 2.45; 95% confidence interval: 1.61, 3.71); however,
      subsequent infections were associated with diarrhea only in children aged less
      than 6 months. This observation that natural infection did not confer protection
      during the first 6 months of life poses a challenge to vaccine development.

PMID- 11447052
TI  - Statistical inference for the area under the receiver operating characteristic
      curve in the presence of random measurement error.
AB  - The area under the receiver operating characteristic curve is the most commonly
      used measure of the ability of a biomarker to distinguish between two
      populations. Some markers are subject to substantial measurement error. Under
      normality assumptions, the authors develop a confidence interval procedure for
      the area under the receiver operating characteristic curve that adjusts for
      measurement error. This procedure assumes the availability of data from a
      reliability study of the biomarker. A simulation study was used to check the
      validity of the proposed confidence interval. Furthermore, it was shown that not
      adjusting for measurement error could result in a serious understatement of the
      effectiveness of the biomarker.

PMID- 11447053
TI  - Use of an automated database to evaluate markers for early detection of
      pregnancy.
AB  - The objective of this study was to develop and validate algorithms to detect
      pregnancies from the time of first clinical recognition by using Kaiser
      Permanente automated databases from Portland, Oregon. In 1993--1994, the authors
      evaluated these databases retrospectively to identify markers indicative of
      initial clinical detection of pregnancy and pregnancy outcomes. Pregnancy markers
      were found for 99% of the women for whom pregnancy outcomes were included in the
      automated databases, and pregnancy outcomes were identified for 77% of the women
      for whom there were pregnancy markers. The earliest marker most predictive of a
      pregnancy outcome was a positive human chorionic gonadotropin test; least
      predictive was an obstetric outpatient visit. Medical record review indicated
      that in a sample of women with pregnancy markers in the database, an estimated 6%
      of pregnancy outcomes (primarily early fetal deaths and elective terminations)
      were lost. Pregnancies were first captured in automated databases 6--8 weeks
      after the last menstrual period, and a combination of a positive human chorionic
      gonadotropin test and an outpatient obstetric visit was the most sensitive and
      specific early marker of pregnancy. When combined with automated pharmacy
      records, these databases may be valuable tools for evaluating prescription drug
      effects on all major outcomes of clinically recognized pregnancies.

PMID- 11447054
TI  - Re: "Latex sensitization in health care workers and in the US general
      population".

PMID- 11447055
TI  - Biomechanics of cardiovascular development.
AB  - It long has been known that mechanical forces play a role in the development of
      the cardiovascular system, but only recently have biomechanical engineers begun
      to explore this field. This paper reviews some of this work. First, an overview
      of the relevant biology is discussed. Next, a mechanical theory is presented that
      can be used to model developmental processes. The theory includes the effects of
      finite volumetric growth and active contractile forces. Finally, applications of
      this and other theories to problems of cardiovascular development are discussed,
      and some future directions are suggested. The intent is to stimulate further
      interest among engineers in this important area of research.

PMID- 11447056
TI  - Fundamentals of impact biomechanics: Part 2--Biomechanics of the abdomen, pelvis,
      and lower extremities.
AB  - This is the second of two chapters (the first chapter appeared in the Annual
      Review of Biomedical Engineering, 2000, 2:55-81) dealing with some 60 years of
      accumulated knowledge in the field of impact biomechanics. The regions covered in
      the first chapter were the head, neck, and thorax. In this chapter, the abdomen,
      pelvis, and lower extremities are discussed. The thoracolumbar spine is not
      covered because of length limitations and the low frequency of injury to this
      area from automotive accidents. Again, in the cited results, the reader needs to
      be keenly aware of the wide variation in human response and tolerance. This is
      due primarily to the large biological variations among humans and to the effects
      of aging. Average values that are useful in design cannot be applied to
      individuals.

PMID- 11447057
TI  - Cardiac energy metabolism: models of cellular respiration.
AB  - The heart requires a large amount of energy to sustain both ionic homeostasis and
      contraction. Under normal conditions, adenosine triphosphate (ATP) production
      meets this demand. Hence, there is a complex regulatory system that adjusts
      energy production to meet this demand. However, the mechanisms for this control
      are a topic of active debate. Energy metabolism can be divided into three main
      stages: substrate delivery to the tricarboxylic acid (TCA) cycle, the TCA cycle,
      and oxidative phosphorylation. Each of these processes has multiple control
      points and exerts control over the other stages. This review discusses the basic
      stages of energy metabolism, mechanisms of control, and the mathematical and
      computational models that have been used to study these mechanisms.

PMID- 11447058
TI  - The process and development of image-guided procedures.
AB  - Medical imaging has been used primarily for diagnosis. In the past 15 years there
      has been an emergence of the use of images for the guidance of therapy. This
      process requires three-dimensional localization devices, the ability to register
      medical images to physical space, and the ability to display position and
      trajectory on those images. This paper examines the development and state of the
      art in those processes.

PMID- 11447059
TI  - Can we model nitric oxide biotransport? A survey of mathematical models for a
      simple diatomic molecule with surprisingly complex biological activities.
AB  - Nitric oxide (NO) is a remarkable free radical gas whose presence in biological
      systems and whose astonishing breadth of physiological and pathophysiological
      activities have only recently been recognized. Mathematical models for NO
      biotransport, just beginning to emerge in the literature, are examined in this
      review. Some puzzling and paradoxical properties of NO may be understood by
      modeling proposed mechanisms with known parameters. For example, it is not
      obvious how NO can survive strong scavenging by hemoglobin and still be a potent
      vasodilator. Recent models do not completely explain how tissue NO can reach
      effective levels in the vascular wall, and they point toward mechanisms that need
      further investigation. Models help to make sense of extremely low partial
      pressures of NO exhaled from the lung and may provide diagnostic information. The
      role of NO as a gaseous neurotransmitter is also being understood through
      modeling. Studies on the effects of NO on O2 transport and metabolism, also
      reviewed, suggest that previous mathematical models of transport of O2 to tissue
      need to be revised, taking the biological activity of NO into account.

PMID- 11447060
TI  - Visual prostheses.
AB  - The development of man-made systems to restore functional vision in the
      profoundly blind has recently undergone a renaissance that has been fueled by a
      combination of celebrity and government interest, advances in the field of
      bioengineering, and successes with existing neuroprosthetic systems. This chapter
      presents the underlying physiologic principles of artificial vision, discusses
      three contemporary approaches to restoring functional vision in the blind, and
      concludes by presenting several relevant questions to vision prostheses. While
      there has been significant progress in the individual components constituting an
      artificial vision system, the remaining challenge of integrating these components
      with each other and the nervous system does not lie strictly in the realm of
      neuroscience, medicine, or engineering but at the interface of all three. In
      spite of the apparent complexity of an artificial vision system, it is not
      unreasonable to be optimistic about its eventual success.

PMID- 11447061
TI  - Micro- and nanomechanics of the cochlear outer hair cell.
AB  - Outer hair cell electromotility is crucial for the amplification, sharp frequency
      selectivity, and nonlinearities of the mammalian cochlea. Current modeling
      efforts based on morphological, physiological, and biophysical observations
      reveal transmembrane potential gradients and membrane tension as key independent
      variables controlling the passive and active mechanics of the cell. The cell's
      mechanics has been modeled on the microscale using a continuum approach
      formulated in terms of effective (cellular level) mechanical and electric
      properties. Another modeling approach is nanostructural and is based on the
      molecular organization of the cell's membranes and cytoskeleton. It considers
      interactions between the components of the composite cell wall and the molecular
      elements within each of its components. The methods and techniques utilized to
      increase our understanding of the central role outer hair cell mechanics plays in
      hearing are also relevant to broader research questions in cell mechanics, cell
      motility, and cell transduction.

PMID- 11447062
TI  - New DNA sequencing methods.
AB  - The Human Genome Project and other major genomic sequencing projects have pushed
      the development of sequencing technology. In the past six years alone, instrument
      throughput has increased 15-fold. New technologies are now on the horizon that
      could yield massive increases in our capacity for de novo DNA sequencing. This
      review presents a summary of state-of-the-art technologies for genomic sequencing
      and describes technologies that may be candidates for the next generation of DNA
      sequencing instruments.

PMID- 11447063
TI  - Vascular tissue engineering.
AB  - The development of a tissue-engineered blood vessel substitute has motivated much
      of the research in the area of cardiovascular tissue engineering over the past 20
      years. Several methodologies have emerged for constructing blood vessel
      replacements with biological functionality. These include cell-seeded collagen
      gels, cell-seeded biodegradable synthetic polymer scaffolds, cell self-assembly,
      and acellular techniques. This review details the most recent developments, with
      a focus on core technologies and construct development. Specific examples are
      discussed to illustrate both the benefits and shortcomings of each methodology,
      as well as to underline common themes. Finally, a brief perspective on challenges
      for the future is presented.

PMID- 11447064
TI  - Computer modeling and simulation of human movement.
AB  - Recent interest in using modeling and simulation to study movement is driven by
      the belief that this approach can provide insight into how the nervous system and
      muscles interact to produce coordinated motion of the body parts. With the
      computational resources available today, large-scale models of the body can be
      used to produce realistic simulations of movement that are an order of magnitude
      more complex than those produced just 10 years ago. This chapter reviews how the
      structure of the neuromusculoskeletal system is commonly represented in a
      multijoint model of movement, how modeling may be combined with optimization
      theory to simulate the dynamics of a motor task, and how model output can be
      analyzed to describe and explain muscle function. Some results obtained from
      simulations of jumping, pedaling, and walking are also reviewed to illustrate the
      approach.

PMID- 11447065
TI  - Stem cell bioengineering.
AB  - Tissue engineering and cellular therapies, either on their own or in combination
      with therapeutic gene delivery, have the potential to significantly impact
      medicine. Implementation of technologies based on these approaches requires a
      readily available source of cells for the generation of cells and tissues outside
      a living body. Because of their unique capacity to regenerate functional tissue
      for the lifetime of an organism, stem cells are an attractive "raw material" for
      multiple biotechnological applications. By definition they are self-renewing
      because on cell division they can generate daughter stem cells. They are also
      multipotent because they can differentiate into numerous specialized, functional
      cells. Recent findings have shown that stem cells exist in most, if not all,
      tissues, and that stem cell tissue specificity may be more flexible than
      originally thought. Although the potential for producing novel cell-based
      products from stem cells is large, currently there are no effective
      technologically relevant methodologies for culturing stem cells outside the body,
      or for reproducibly stimulating them to differentiate into functional cells. A
      mechanistic understanding of the parameters important in the control of stem cell
      self-renewal and lineage commitment is thus necessary to guide the development of
      bioprocesses for the ex vivo culture of stem cells and their derivates.

PMID- 11447066
TI  - Biomechanics of trabecular bone.
AB  - Trabecular bone is a complex material with substantial heterogeneity. Its elastic
      and strength properties vary widely across anatomic sites, and with aging and
      disease. Although these properties depend very much on density, the role of
      architecture and tissue material properties remain uncertain. It is interesting
      that the strains at which the bone fails are almost independent of density.
      Current work addresses the underlying structure-function relations for such
      behavior, as well as more complex mechanical behavior, such as multiaxial
      loading, time-dependent failure, and damage accumulation. A unique tool for
      studying such behavior is the microstructural class of finite element models,
      particularly the "high-resolution" models. It is expected that with continued
      progress in this field, substantial insight will be gained into such important
      problems as osteoporosis, bone fracture, bone remodeling, and design/analysis of
      bone-implant systems. This article reviews the state of the art in trabecular
      bone biomechanics, focusing on the mechanical aspects, and attempts to identify
      important areas of current and future research.

PMID- 11447067
TI  - Soft lithography in biology and biochemistry.
AB  - Soft lithography, a set of techniques for microfabrication, is based on printing
      and molding using elastomeric stamps with the patterns of interest in basrelief.
      As a technique for fabricating microstructures for biological applications, soft
      lithography overcomes many of the shortcomings of photolithography. In
      particular, soft lithography offers the ability to control the molecular
      structure of surfaces and to pattern the complex molecules relevant to biology,
      to fabricate channel structures appropriate for microfluidics, and to pattern and
      manipulate cells. For the relatively large feature sizes used in biology (> or =
      50 microns), production of prototype patterns and structures is convenient,
      inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are
      particularly easy to pattern by soft lithography, and they provide exquisite
      control over surface biochemistry.

PMID- 11447068
TI  - Image-guided acoustic therapy.
AB  - The potential role of therapeutic ultrasound in medicine is promising. Currently,
      medical devices are being developed that utilize high-intensity focused
      ultrasound as a noninvasive method to treat tumors and to stop bleeding
      (hemostasis). The primary advantage of ultrasound that lends the technique so
      readily to use in noninvasive therapy is its ability to penetrate deep into the
      body and deliver to a specific site thermal or mechanical energy with
      submillimeter accuracy. Realizing the full potential of acoustic therapy,
      however, requires precise targeting and monitoring. Fortunately, several imaging
      modalities can be utilized for this purpose, thus leading to the concept of image
      guided acoustic therapy. This article presents a review of high-intensity focused
      ultrasound therapy, including its mechanisms of action, the imaging modalities
      used for guidance and monitoring, some current applications, and the requirements
      and technology associated with this exciting and promising field.

PMID- 11447069
TI  - Control motifs for intracellular regulatory networks.
AB  - A number of technological innovations are yielding unprecedented data on the
      networks of biochemical, genetic, and biophysical reactions that underlie
      cellular behavior and failure. These networks are composed of hundreds to
      thousands of chemical species and structures, interacting via nonlinear and
      possibly stochastic physical processes. A central goal of modern biology is to
      optimally use the data on these networks to understand how their design leads to
      the observed cellular behaviors and failures. Ultimately, this knowledge should
      enable cellular engineers to redesign cellular processes to meet industrial needs
      (such as optimal natural product synthesis), aid in choosing the most effective
      targets for pharmaceuticals, and tailor treatment for individual genotypes. The
      size and complexity of these networks and the inevitable lack of complete data,
      however, makes reaching these goals extremely difficult. If it proves possible to
      modularize these networks into functional subnetworks, then these smaller
      networks may be amenable to direct analysis and might serve as regulatory motifs.
      These motifs, recurring elements of control, may help to deduce the structure and
      function of partially known networks and form the basis for fulfilling the goals
      described above. A number of approaches to identifying and analyzing control
      motifs in intracellular networks are reviewed.

PMID- 11447070
TI  - Respiratory fluid mechanics and transport processes.
AB  - The field of respiratory flow and transport has experienced significant research
      activity over the past several years. Important contributions to the knowledge
      base come from pulmonary and critical care medicine, surgery, physiology,
      environmental health sciences, biophysics, and engineering. Several disciplines
      within engineering have strong and historical ties to respiration including
      mechanical, chemical, civil/environmental, aerospace and, of course, biomedical
      engineering. This review draws from a wide variety of scientific literature that
      reflects the diverse constituency and audience that respiratory science has
      developed. The subject areas covered include nasal flow and transport, airway gas
      flow, alternative modes of ventilation, nonrespiratory gas transport, aerosol
      transport, airway stability, mucus transport, pulmonary acoustics, surfactant
      dynamics and delivery, and pleural liquid flow. Within each area are a number of
      subtopics whose exploration can provide the opportunity of both depth and breadth
      for the interested reader.

PMID- 11447071
TI  - Hypertrophic cardiomyopathy: from bedside to bench...and now back again?

PMID- 11447072
TI  - Tissue Doppler imaging consistently detects myocardial abnormalities in patients
      with hypertrophic cardiomyopathy and provides a novel means for an early
      diagnosis before and independently of hypertrophy.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH), the clinical hallmark of familial
      hypertrophic cardiomyopathy (FHCM), is absent in a significant number of subjects
      with causal mutations. In transgenic rabbits that fully recapitulate the FHCM
      phenotype, reduced myocardial tissue Doppler (TD) velocities accurately
      identified the mutant rabbits, even in the absence of LVH. We tested whether
      humans with FHCM also consistently showed reduced myocardial TD velocities,
      irrespective of LVH. METHODS AND RESULTS: We performed 2D and Doppler
      echocardiography and TD imaging in 30 subjects with FHCM, 13 subjects who were
      positive for various mutations but did not have LVH, and 30 age- and sex-matched
      controls (all adults; 77% women). LV wall thickness and mass were significantly
      greater in FHCM subjects (P<0.01 versus those without LVH and controls). There
      were no significant differences in 2D echocardiographic, mitral, and pulmonary
      venous flow indices between mutation-positives without LVH and controls. In
      contrast, systolic and early diastolic TD velocities were significantly lower in
      both mutation-positives without LVH and in FHCM patients than in controls
      (P<0.001). Reduced TD velocities had a sensitivity of 100% and a specificity of
      93% for identifying mutation-positives without LVH. CONCLUSIONS: Myocardial
      contraction and relaxation velocities, detected by TD imaging, are reduced in
      FHCM, including in those without LVH. Before and independently of LVH, TD imaging
      is an accurate and sensitive method for identifying subjects who are positive for
      FHCM mutations.

PMID- 11447073
TI  - Cardiac gene delivery with cardiopulmonary bypass.
AB  - BACKGROUND: Cardiac gene therapy offers the possibility of enhancing myocardial
      performance in the compromised heart. However, current gene delivery techniques
      have limited myocardial transgene expression and pose the risk of extracardiac
      expression. Isolation of the coronary circulation during cardiac surgery may
      allow for more efficient and cardiac-selective gene delivery in a clinically
      relevant model. Methods and Results-- Neonatal piglets (3 kg) underwent a median
      sternotomy and cardiopulmonary bypass, followed by aortic cross-clamping with 30
      minutes of cardioplegic arrest. Adenoviral vectors containing transgenes for
      either beta-galactosidase (adeno-beta-gal, n=11) or the human beta(2)-adrenergic
      receptor (adeno-beta(2)-AR, n=15) were administered through the cardioplegia
      cannula immediately after arrest and were allowed to dwell in the coronary
      circulation during the cross-clamp period. After 1 week, the animals were killed,
      and their heart, lungs, and liver were excised and examined for gene expression.
      Analysis of beta-galactosidase staining revealed transmural myocardial gene
      expression among animals receiving adeno-beta-gal. No marker gene expression was
      detected in liver or lung tissue. beta-AR density in the left ventricle after
      adeno-beta(2)-AR delivery was 396+/-85% of levels in control animals (P<0.01).
      Animals receiving adeno-beta(2)-AR and control animals demonstrated similar beta
      AR density in both the liver (114+/-8% versus 100+/-9%, P=NS) and lung (114+/-7%
      versus 100+/-9%, P=NS). There was no evidence of cardiac inflammation.
      CONCLUSIONS: By using cardiopulmonary bypass and cardioplegic arrest,
      intracoronary delivery of adenoviral vectors resulted in efficient myocardial
      uptake and expression. Undetectable transgene expression in liver or lung tissue
      suggests cardiac-selective expression.

PMID- 11447074
TI  - Enhanced generation of reactive oxygen species in the limb skeletal muscles from
      a murine infarct model of heart failure.
AB  - BACKGROUND: The generation of reactive oxygen species (ROS) is enhanced in the
      failing myocardium. We hypothesized that ROS were also increased in the limb
      skeletal muscles in heart failure. Methods and Results-- Myocardial infarction
      (MI) was created in mice by ligating the left coronary artery. After 4 weeks, the
      left ventricle was dilated and contractility was diminished by echocardiography.
      Left ventricular end-diastolic pressure was elevated after MI in association with
      an increase in lung weight/body weight and the presence of pleural effusion. The
      generation of ROS in the limb muscles, including the soleus and gastrocnemius
      muscles, which were excised after MI, was measured by electron spin resonance
      spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxy
      TEMPO). Overall, generation was increased, but it was attenuated in the presence
      of dimethylthiourea or 4,5-dihydroxy-1,2-benzenedisulfonic disodium salt in the
      reaction mixture, indicating increased generation of hydroxyl radicals
      originating from superoxide anion. Thiobarbituric acid-reactive substance
      formation was also increased in muscles after MI. Mitochondrial complex I and III
      activities were both decreased after MI, which may have caused the functional
      uncoupling of the respiratory chain and ROS production. Antioxidant enzyme
      activities, including superoxide dismutase, catalase, and glutathione peroxidase,
      were comparable between groups. CONCLUSIONS: Skeletal muscle in post-MI heart
      failure expressed an increased amount of ROS in association with ROS-mediated
      lipid peroxidation. This supports the hypothesis that oxidative stress may cause
      (at least in part) skeletal muscle dysfunction in heart failure.

PMID- 11447075
TI  - Aldosterone induces angiotensin-converting-enzyme gene expression in cultured
      neonatal rat cardiocytes.
AB  - BACKGROUND: The cardiac renin-angiotensin-aldosterone system is activated in
      failing hearts in proportion to the severity of the disease. We hypothesized that
      a positive feedback mechanism might exist within this system and contribute to
      the progression of the heart failure. Methods and Results-- To test this
      hypothesis, we examined whether angiotensin II or aldosterone induces the
      expression of angiotensin-converting-enzyme (ACE) mRNA in cultured neonatal rat
      ventricular cardiocytes. Expression of ACE mRNA was detected and quantified using
      real-time reverse transcription-polymerase chain reaction. Exposure to
      angiotensin II (10(-5) mol/L) for 24 hours had no significant effect on the
      expression of ACE mRNA (0.7+/-0.5-fold versus control, P=NS), but similar
      treatment with aldosterone (10(-5) mol/L) induced a 23.3+/-7.9-fold increase
      (P<0.01) in ACE mRNA expression. The effect of aldosterone was both time-
      (maximal effect, 24 hours) and dose-dependent (EC(50), 4x10(-7) mol/L), and it
      was significantly (P<0.01) inhibited by spironolactone, a specific
      mineralocorticoid receptor antagonist. CONCLUSIONS: Aldosterone upregulates ACE
      mRNA expression, which is blocked by spironolactone in neonatal rat cardiocytes.
      Thus, spironolactone may suppress the progression of heart failure by blocking
      the effects of aldosterone and angiotensin II.

PMID- 11447076
TI  - Platelet glycoprotein IIIa Pl(a) polymorphism, fibrinogen, and platelet
      aggregability: The Framingham Heart Study.
AB  - BACKGROUND: Recent data suggest that the Pl(A2) allele of the platelet
      glycoprotein IIIa receptor may be a genetic risk factor for cardiovascular
      disease. We previously reported that the Pl(A2) allele was associated with
      increased platelet aggregability, as indicated by lower epinephrine threshold
      concentrations. Paradoxically, however, it has been reported that Pl(A2)-positive
      platelets have reduced fibrinogen binding. Because fibrinogen mediates platelet
      aggregability, we hypothesized that plasma fibrinogen levels may interact with
      Pl(A) genotype in modulating platelet aggregability. Methods and Results--
      Glycoprotein IIIa Pl(A) genotype, fibrinogen level, and platelet aggregability
      were ascertained in 1340 subjects enrolled into the Framingham Offspring Study.
      Platelet aggregability was evaluated by the Born method. Higher fibrinogen levels
      were associated with increased epinephrine-induced aggregation (P=0.002) and a
      trend for ADP-induced aggregation (P=0.07). The fibrinogen effect was genotype
      specific, however, in that the increase in platelet aggregability with higher
      fibrinogen was present for the Pl(A1/A1) genotype (P=0.0005 and P=0.03 for
      epinephrine- and ADP-induced aggregation, respectively) but not for the Pl(A2)
      positive genotype (P>0.90). CONCLUSION: Higher fibrinogen levels were associated
      with increased platelet aggregability. However, the association between
      fibrinogen and platelet aggregability was genotype specific. This interaction may
      be responsible for the conflicting findings regarding Pl(A) genotype and platelet
      aggregability. Further study of this gene-environment interaction may provide
      insight into cardiovascular disease risk.

PMID- 11447077
TI  - C-reactive protein, insulin resistance, central obesity, and coronary heart
      disease risk in Indian Asians from the United Kingdom compared with European
      whites.
AB  - BACKGROUND: Indian Asians in the United Kingdom have increased coronary heart
      disease (CHD) mortality compared with European whites, but the causes are not
      well understood. Increased circulating concentrations of C-reactive protein (CRP)
      are an independent risk factor for CHD. Therefore, we investigated this marker of
      inflammation in healthy UK Indian Asian and European white men. Methods and
      Results-- We measured serum CRP concentrations and conventional CHD risk factors
      in 1025 healthy male subjects (518 Indian Asians and 507 European whites) aged 35
      to 60 years who were recruited at random from general practitioner lists. The
      geometric mean CRP concentration was 17% higher (95% confidence interval, 3% to
      33%) in Indian Asians compared with European whites. CRP values were strongly
      associated with conventional CHD risk factors, measures of obesity, and metabolic
      disturbances associated with insulin resistance in both racial groups. The
      difference in CRP concentrations between Indian Asians and European whites
      remained after adjustment for conventional CHD risk factors but was eliminated by
      an adjustment for central obesity and insulin resistance score in Asians. On the
      basis of these results, we estimate that the processes underlying elevated CRP
      and/or increased CRP production itself are associated with an approximately 14%
      increase in population CHD risk among Indian Asians compared with European
      whites. CONCLUSIONS: CRP concentrations are higher in healthy Indian Asians than
      in European whites and are accounted for by greater central obesity and insulin
      resistance in Indian Asians. Our results suggest that inflammation or other
      mechanisms underlying elevated CRP values may contribute to the increased CHD
      risk among Indian Asians.

PMID- 11447078
TI  - Short- and long-term black tea consumption reverses endothelial dysfunction in
      patients with coronary artery disease.
AB  - BACKGROUND: Epidemiological studies suggest that tea consumption decreases
      cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial
      dysfunction has been associated with coronary artery disease and increased
      oxidative stress. Some antioxidants have been shown to reverse endothelial
      dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To
      test the hypothesis that tea consumption will reverse endothelial dysfunction, we
      randomized 66 patients with proven coronary artery disease to consume black tea
      and water in a crossover design. Short-term effects were examined 2 hours after
      consumption of 450 mL tea or water. Long-term effects were examined after
      consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the
      brachial artery was examined at baseline and after each intervention with
      vascular ultrasound. Fifty patients completed the protocol and had technically
      suitable ultrasound measurements. Both short- and long-term tea consumption
      improved endothelium- dependent flow-mediated dilation of the brachial artery,
      whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA).
      Tea consumption had no effect on endothelium-independent nitroglycerin-induced
      dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect
      on flow-mediated dilation. Plasma flavonoids increased after short- and long-term
      tea consumption. CONCLUSIONS: Short- and long-term black tea consumption reverses
      endothelial vasomotor dysfunction in patients with coronary artery disease. This
      finding may partly explain the association between tea intake and decreased
      cardiovascular disease events.

PMID- 11447079
TI  - Fractional flow reserve in patients with prior myocardial infarction.
AB  - BACKGROUND: Fractional flow reserve (FFR), an index of coronary stenosis
      severity, can be calculated from the ratio of hyperemic distal to proximal
      coronary pressure. An FFR value of 0.75 can distinguish patients with normal and
      abnormal noninvasive stress testing in case of normal left ventricular function.
      The present study aimed at investigating the value of FFR in patients with a
      prior myocardial infarction. Methods and Results-- In 57 patients who had
      sustained a myocardial infarction >/=6 days earlier, myocardial perfusion single
      photon emission scintigraphy (SPECT) imaging and FFR were obtained before and
      after angioplasty. The sensitivity and specificity of the 0.75 value of FFR to
      detect flow maldistribution at SPECT imaging were 82% and 87%. The concordance
      between the FFR and SPECT imaging was 85% (P<0.001). When only truly positive and
      truly negative SPECT imaging were considered, the corresponding values were 87%,
      100%, and 94% (P<0.001). Patients with positive SPECT imaging before angioplasty
      had a significantly lower FFR than patients with negative SPECT imaging (0.52+/
      0.18 versus 0.67+/-0.16, P=0.0079) but a significantly higher left ventricular
      ejection fraction (63+/-10% versus 52+/-10%, P=0.0009) despite a similar degree
      of diameter stenosis (67+/-13% versus 68+/-16%, P=NS). A significant inverse
      correlation was found between LVEF and FFR (R=0.29, P=0.049). CONCLUSIONS: The
      present data indicate (1) that the 0.75 cutoff value of FFR to distinguish
      patients with positive from patients with negative SPECT imaging is valid after a
      myocardial infarction and (2) that for a similar degree of stenosis, the value of
      FFR depends on the mass of viable myocardium.

PMID- 11447080
TI  - Abciximab suppresses the rise in levels of circulating inflammatory markers after
      percutaneous coronary revascularization.
AB  - BACKGROUND: Previous investigators have shown that systemic markers of
      inflammation may be increased in patients with acute ischemic syndromes or after
      percutaneous coronary revascularization and that persistent elevation in these
      markers is predictive of excess risk of subsequent adverse cardiac events. By
      virtue of its cross-reactivity with the glycoprotein IIb/IIIa, avbeta3, and
      alphaMbeta2 receptors, abciximab may reduce inflammatory processes. Methods and
      Results-- Assays for the inflammatory markers C-reactive protein, interleukin-6,
      and tumor necrosis factor-alpha were performed on serum samples obtained from 160
      patients in a placebo-controlled, randomized trial of abciximab during
      angioplasty. Eighty patients each had received a placebo or abciximab bolus plus
      a 12-hour infusion. Serum samples were drawn at baseline (before
      revascularization), 24 to 48 hours after study drug administration, and 4 weeks
      after study drug administration. Between baseline and 24 to 48 hours, the
      increase in C-reactive protein was 32% less in patients receiving abciximab than
      placebo (P=0.025); the rise in interleukin-6 levels was 76% less in the abciximab
      group (P<0.001); and the rise in tumor necrosis factor-alpha levels was 100% less
      with abciximab therapy (P=0.112). By 4 weeks, most marker levels had returned to
      baseline, with no significant differences between placebo and abciximab groups.
      CONCLUSIONS: Systemic markers of inflammation increase in the first 24 to 48
      hours after angioplasty, but the magnitude of that rise is diminished by
      periprocedural abciximab. Some of the long-term clinical benefit derived from
      this agent may be related to an anti-inflammatory effect.

PMID- 11447081
TI  - Inflammatory left ventricular microaneurysms as a cause of apparently idiopathic
      ventricular tachyarrhythmias.
AB  - BACKGROUND: We sought to investigate the arrhythmogenic role, incidence,
      treatment, and prognosis of inflammatory left ventricular (LV) microaneurysms in
      patients with apparently idiopathic ventricular tachyarrhythmias. Methods and
      Results-- We studied 156 consecutive patients (71 men, 85 women; mean age, 44.1+/
      11.8 years) with severe ventricular arrhythmias and normal 2D echo cardiac
      parameters by coronary and ventricular angiography, biventricular endomyocardial
      biopsy, and electrophysiological study. Polymerase chain reaction was used to
      detect genomic sequences of enterovirus, adenovirus, Epstein Barr virus,
      cytomegalovirus, herpes simplex viruses, influenza A and B viruses, and hepatitis
      C virus in frozen endomyocardial samples. Of these patients, 15 (9.6%) showed
      angiographic evidence of single or multiple LV microaneurysms. All 15 patients
      had recurrent episodes of ventricular tachycardia with right bundle-branch block
      morphology, and the arrhythmias originated within or close to the aneurysms in
      those patients (n=6) undergoing ventricular mapping. A lymphocytic myocarditis
      was observed in LV biopsies of all patients and in the right ventricles of 3
      patients. Polymerase chain reaction analysis was performed in 12 and viral
      genomes were found in 5 (42%): hepatitis C virus in 2, enterovirus in 2, and
      influenza virus A in 1. The patients were treated with antiarrhythmics, and
      cardiac function was preserved for the next 47+/-39.5 months of follow-up. No
      major clinical event was registered, and arrhythmias were successfully treated by
      antiarrhythmics. CONCLUSIONS: Inflammatory LV microaneurysms, often of viral
      origin, are a consistent cause of apparently idiopathic ventricular arrhythmias.
      Their prognosis so far has been benign, and aggressive therapeutic strategies
      have been unnecessary.

PMID- 11447082
TI  - Impaired myofibrillar energetics and oxidative injury during human atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with severe contractile
      dysfunction and structural and electrophysiological remodeling. Mechanisms
      responsible for impaired contractility are undefined, and current therapies do
      not address this dysfunction. We have found that myofibrillar creatine kinase (MM
      CK), an important controller of myocyte contractility, is highly sensitive to
      oxidative injury, and we hypothesized that increased oxidative stress and
      energetic impairment during AF could contribute to contractile dysfunction.
      Methods and Results-- Right atrial appendages were obtained from AF patients
      undergoing the Maze procedure and from control patients who were in normal sinus
      rhythm and undergoing cardiac surgery. MM-CK activity was reduced in AF patients
      compared with controls (25.4+/-3.4 versus 18.2+/-3.8 micromol/mg of myofibrillar
      protein per minute; control versus AF; P<0.05). No reduction in total CK activity
      or myosin ATPase activity was detected. This selective reduction in MM-CK
      activity was associated with increased relative expression of the beta-myosin
      isoform (25+/-6 versus 63+/-5%beta, CTRL versus AF; P<0.05). Western blotting of
      AF myofibrillar isolates demonstrated no changes in protein composition but
      showed increased prevalence of protein oxidation as detected by Western blotting
      for 3-nitrotyrosine (peroxynitrite biomarker) and protein carbonyls (hydroxyl
      radical biomarker; P<0.05). Patterns of these oxidative markers were distinct,
      which suggests discrete chemical events and differential protein vulnerabilities
      in vivo. MM-CK inhibition was statistically correlated to extent of nitration
      (P<0.01) but not to carbonyl presence. CONCLUSIONS: The present results provide
      novel evidence of oxidative damage in human AF that altered myofibrillar
      energetics may contribute to atrial contractile dysfunction and that protein
      nitration may be an important participant in this condition.

PMID- 11447083
TI  - Platelet reactivity characterized prospectively: a determinant of outcome 90 days
      after percutaneous coronary intervention.
AB  - BACKGROUND: Platelet activation is pivotal in the pathogenesis of complications
      after percutaneous coronary interventions (PCI). We previously reported
      substantial interindividual variability in activation of glycoprotein (GP)
      IIb/IIIa in response to a low concentration of ADP. We assessed GP IIb/IIIa
      activation prospectively to determine whether this could differentiate patients
      at low risk from those at high risk for complications early and late after PCI.
      Methods and Results-- A total of 112 patients undergoing PCI were studied.
      Platelet reactivity was determined with the use of flow cytometry. Patients were
      classified into high and low platelet reactivity groups on the basis of extent of
      activation of GP IIb/IIIa in response to 0.2 micromol/L ADP. The median value was
      used for differentiation. The incidence during 90-day follow-up interval of a
      composite end point (myocardial infarction, urgent revascularization, or repeat
      revascularization) was determined in each group. Follow up was completed in all
      112 patients. The 2 groups were similar with respect to diverse clinical
      characteristics. Nevertheless, the incidence of the composite end point occurred
      in 26.8% of the high and 7.1% in the low platelet reactivity group (P=0.01). The
      difference in the composite end point was most striking during the 30- to 90-day
      interval after PCI (16.7% versus 1.9%; P=0.02). Repeat revascularization was more
      frequent in those with increased platelet reactivity (17.9% versus with 3.6%,
      P=0.029). CONCLUSIONS: Prospective assessment of platelet GP IIb/IIIa activation
      permits stratification of patients into low- and high-risk groups with respect to
      adverse events after PCI.

PMID- 11447084
TI  - Polymorphism in the beta(1)-adrenergic receptor gene and hypertension.
AB  - BACKGROUND: The Arg389 variant of the beta(1)-adrenergic receptor gene mediates a
      higher isoproterenol-stimulated adenylate cyclase activity than the Gly389
      variant in vitro. We investigated whether the Arg389Gly or the Ser49Gly
      polymorphism is associated with hypertension in Scandinavians. Methods and
      Results-- A total of 292 unrelated, nondiabetic, hypertensive patients and 265
      unrelated healthy control subjects were included in a case-control association
      study. From 118 families, 102 nondiabetic sibling pairs without antihypertensive
      medication who were discordant for the Arg389Gly polymorphism were selected for a
      sibling study. Allele and genotype frequencies of the Arg389Gly and Ser49Gly
      polymorphisms were compared between hypertensive patients and normotensive
      control subjects. Blood pressure and heart rate were compared between carriers of
      the different genotypes. In the case-control study, the age- and body mass index
      adjusted odds ratio for hypertension in subjects homozygous for the Arg389 allele
      was 1.9 (95% confidence interval, 1.3 to 2.7; P=0.0005) when compared with
      carriers of 1 or 2 copies of the Gly389 allele. The genotype-discordant sibling
      pair analysis revealed that siblings homozygous for the Arg389 allele had
      significantly higher diastolic blood pressures (79.4+/-9.9 versus 76.0+/-10.1 mm
      Hg; P=0.003) and higher heart rates (68.3+/-11.0 versus 65.1+/-9.4 bpm; P=0.02)
      than siblings carrying 1 or 2 copies of the Gly389 allele. The Ser49Gly
      polymorphism was not associated with hypertension. CONCLUSION: Our data suggest
      that individuals homozygous for the Arg389 allele of the beta(1)-adrenergic
      receptor gene are at increased risk to develop hypertension.

PMID- 11447085
TI  - Prognostic significance of endothelial dysfunction in hypertensive patients.
AB  - BACKGROUND: Forearm endothelial dysfunction, characterized by an impaired
      vasodilating response to acetylcholine (ACh), may be associated with several
      cardiovascular risk factors, including essential hypertension. Although the
      prognostic value of coronary endothelial dysfunction has been demonstrated, that
      of forearm endothelial dysfunction is still unknown. Methods and Results--
      Endothelium-dependent and -independent vasodilation was investigated in 225 never
      treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of
      increasing doses of ACh and sodium nitroprusside. Patients were divided into
      tertiles on the basis of their increase in ACh-stimulated forearm blood flow
      (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and
      group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5
      of months (range, 4 to 84 months), there were 29 major adverse events at the
      cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events
      included myocardial infarction, angina, coronary revascularization procedures,
      stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease.
      Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second,
      and third tertiles of peak percent increase in FBF during ACh infusion. The
      excess risk associated with an FBF increase in the first tertile was significant
      (relative risk, 2.084; 95% CI, 1.25 to 3.48; P=0.0049) after controlling for
      individual risk markers, including 24-hour ambulatory blood pressure.
      CONCLUSIONS: Our data suggest that forearm endothelial dysfunction is a marker of
      future cardiovascular events in patients with essential hypertension.

PMID- 11447086
TI  - In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis
      in apolipoprotein E-knockout mice.
AB  - BACKGROUND: A chronic immune response involving proinflammatory T helper cell 1
      (Th1) lymphocyte activation occurs in the atherosclerotic lesion, but whether
      this activation is protective or deleterious remains unclear. Methods and Results
      - We modulated the immune response of the atherosclerosis-prone apolipoprotein E
      deficient (apoE(-/-)) mouse. Eight-week-old apoE(-/-) mice were treated daily
      with pentoxifylline (PTX), a known inhibitor of the Th1 differentiation pathway,
      or PBS (control) for 4 weeks or 12 weeks. Twelve-week PTX treatment reduced
      atherosclerotic lesion size by 60% (P<0.01). PTX-treated mice developed lesions
      that were limited to the degree of fatty streaks. In contrast, control mice
      developed mature fibrofatty atherosclerotic lesions. In parallel, the proportion
      of interferon (IFN)-gamma-producing Th1 splenic lymphocytes was significantly
      reduced by PTX, and lesion size was correlated to the proportion of IFN-gamma(+)
      T cells. In vitro addition of PTX to cultured spleen cells did not modify the
      production of IFN-gamma but increased the production of IL-10 by T cells,
      indicating that PTX does not suppress IFN-gamma production but rather blocks Th1
      polarization while promoting Th2 polarization. CONCLUSIONS: Thus, PTX protected
      mice from atherosclerosis by reducing the Th1 polarization of T helper
      lymphocytes. This study demonstrates that the Th1 immune response associated with
      atherosclerosis is deleterious and that a modulation of the Th1 differentiation
      pathway may provide a new pharmacological tool to treat this disease.

PMID- 11447087
TI  - Detection of monocyte chemoattractant protein-1 receptor expression in
      experimental atherosclerotic lesions: an autoradiographic study.
AB  - BACKGROUND: Monocytes, a common component of atheroma, are attracted to the
      lesion site in response to chemotactic signals, particularly expression of
      monocyte chemoattractant peptide 1 (MCP-1). This study assessed the feasibility
      of using radiolabeled MCP-1 to identify monocytes and macrophages that have
      localized at sites of experimental arterial lesions. Methods and Results-- The
      biodistribution of radiolabeled MCP-1 was determined in normal mice, and
      localization in experimental atheroma was determined in cholesterol-fed rabbits 4
      weeks after arterial injury of the iliac artery (9 rabbits) and the abdominal
      aorta (1 rabbit). Vessels were harvested and autoradiographed after intravenous
      administration of (125)I-labeled MCP-1 and Evans blue dye. The arteries were
      evaluated histologically by hematoxylin and eosin staining and immune staining
      with a monoclonal antibody specific for rabbit macrophages (RAM-11). (125)I-MCP-1
      has a blood clearance half-time of approximately 10 minutes and circulates in
      association with cells. The liver, lungs, and kidneys had the highest
      concentration of (125)I-MCP-1 at 5 and 30 minutes after tracer administration.
      Autoradiograms revealed accumulation of (125)I-MCP-1 in the damaged artery wall,
      with an average ratio of lesion to normal vessel of 6:1 (maximum 45:1). The
      accumulation of (125)I-MCP-1 in the reendothelialized (plaque formation) areas
      was greater than in the deendothelialized (Evans blue-positive) areas (6.55+/
      2.26 versus 4.34+/-1.43 counts/pixel, P<0.05). The uptake of (125)I-MCP-1
      correlated with the number of macrophages per unit area (r=0.85, P<0.0001).
      CONCLUSIONS: Radiolabeled MCP-1 may be a useful tracer for imaging
      monocyte/macrophage-rich experimental atherosclerotic lesions.

PMID- 11447088
TI  - Activation of heat-shock factor by stretch-activated channels in rat hearts.
AB  - BACKGROUND: Previously, we have observed that the isolated, erythrocyte-perfused
      rabbit heart has increased levels of heat-shock protein (HSP) 72 after a mild
      mechanical stress. We hypothesized that stretch-activated ion channels (SACs)
      mediated this increase. Methods and Results-- To test this hypothesis, we
      subjected isolated, perfused rat hearts to mechanical stretch. Gel mobility shift
      assay showed that heat-shock factor (HSF) was activated in hearts with mechanical
      stretch, but not in controls. Supershift experiments demonstrated that HSF1 was
      the transcription factor. Northern blots revealed the concomitant increase in
      HSP72 mRNA in stretched rat hearts. In a separate set of experiments, gadolinium,
      an inhibitor of SACs, was added to the perfusate. Gadolinium inhibited the
      activation of HSF and decreased HSP72 mRNA level. Because gadolinium can inhibit
      both SACs and L-type calcium channels, we perfused a group of hearts with
      diltiazem, a specific L-type calcium channel blocker, to eliminate the
      involvement of L-type calcium channels. Diltiazem failed to inhibit the
      activation of HSF. CONCLUSIONS: Stretch in the rat heart results in activation of
      HSF1 and an increase in HSP72 mRNA through SACs. This represents a novel
      mechanism of HSF activation and may be an important cardiac signaling pathway for
      hemodynamic stress.

PMID- 11447089
TI  - Load versus humoral activation in the genesis of early hypertensive heart
      disease.
AB  - BACKGROUND: The role of load versus angiotensin II (Ang II) and endothelin-1 (ET)
      in the pathogenesis of hypertensive heart disease is controversial. We sought to
      determine whether alterations in cardiac structure and function due to
      hypertension (HTN) were dependent on Ang II or ET activation. Methods and Results
      - Bilateral renal wrapping to produce HTN (n=12) or sham surgery (n=6) was
      performed in adult dogs. Weekly blood pressure, plasma renin activity, Ang II,
      ET, and catecholamines were measured. Systolic (end-systolic elastance, Ees) and
      diastolic (tau) function were assessed in sham and HTN dogs at 5 (HTN-5wk) or 12
      (HTN-12wk) weeks. Ang II and ET were assayed in the left ventricle (LV) and
      kidney. Mean arterial pressure was higher in renal wrap dogs at week 1 (*P<0.05
      versus controls: 139+/-4* versus 123+/-4 mm Hg), week 5 (174+/-7* versus 124+/-4
      mm Hg), and week 12 (181+/-12* versus 124+/-4 mm Hg). LV mass index was increased
      in HTN-5wk (22%*) and HTN-12wk (39%*). LV fibrosis was increased in HTN-12wk. Ees
      was preserved in HTN-5wk and HTN-12wk. tau was increased in HTN-5wk (50+/-3* ms)
      and HTN-12wk (62+/-10* ms) dogs compared with sham (41+/-2 ms). Plasma Ang II,
      ET, catecholamines, and plasma renin activity were unchanged during the
      progressive HTN. Ang II and ET in LV and kidney were not different from controls.
      CONCLUSIONS: Systemic HTN induces LV hypertrophy, myocardial fibrosis, and
      isolated diastolic dysfunction in the absence of local or systemic activation of
      Ang II or ET. These findings suggest that load is the prevailing stimulus for the
      structural and functional changes associated with early hypertensive heart
      disease.

PMID- 11447090
TI  - Exercise training attenuates age-associated diastolic dysfunction in rats.
AB  - BACKGROUND: In contrast to systolic function, which is relatively well preserved
      with advancing age, diastolic function declines steadily after age 30. Our goal
      was to determine whether changes in diastolic function that occur with aging
      could be reversed with exercise training. Methods and Results-- Adult (6-month
      old) and old (24-month-old) Fischer 344/BNF1 rats were studied after either 12
      weeks of treadmill training or normal sedentary cage life. Three aspects of
      diastolic function were studied: (1) left ventricular (LV) filling in vivo via
      Doppler echocardiograph, (2) LV passive compliance, and (3) the degree of
      ischemia-induced LV stiffening. Maximal exercise capacity was lower in the old
      rats (18+/-1 minutes to exhaustion on a standard treadmill) than in the adult
      rats (25+/-1 minutes). Training increased exercise capacity by 43% in the old
      rats and 46% in the adults (to 26+/-1 and 37+/-1 minutes, respectively).
      Echocardiographic indices of LV relaxation were significantly lower in the old
      rats, but with training, they increased back to the levels seen in the adults. LV
      stiffness measured in the isolated, perfused hearts was not affected by age or
      training. Also in the isolated hearts, the LV stiffened more rapidly during low
      flow ischemia in the old hearts than in the adults, but training eliminated this
      age-associated difference in the response to ischemia. CONCLUSIONS: Our findings
      indicate that in rats, some age-associated changes in diastolic function are
      reversible and thus may not be intrinsic to aging but instead secondary to other
      processes, such as deconditioning.

PMID- 11447091
TI  - Optical mapping of ventricular defibrillation in isolated swine right ventricles:
      demonstration of a postshock isoelectric window after near-threshold
      defibrillation shocks.
AB  - BACKGROUND: Investigators who studied ventricular defibrillation by use of
      optical mapping techniques failed to observe an initial defibrillation event
      (isoelectric window or quiescent period) shown by electrode mapping studies. This
      discrepancy has important implications for the mechanisms of defibrillation. The
      purpose of the present study was to demonstrate an optical equivalent of an
      isoelectric window after a near-threshold defibrillation shock. Methods and
      Results-- We studied 10 isolated, perfused swine right ventricles. Upper limit of
      vulnerability was determined by shocks on T waves. A 50% probability of
      successful defibrillation (DFT50) was determined with an up-down algorithm.
      Immediately after unsuccessful defibrillation shock, new wavefronts were
      generated. When the shock strength was low, immediate reinitiation of reentry and
      ventricular fibrillation might occur without a postshock isoelectric window.
      However, if the shock strength was within 50 V of DFT50 (near-threshold), a
      synchronized activation occurred, followed by organized repolarization that ended
      64+/-18 ms after shock. After a period of quiescence (18+/-24 ms), activation
      recurred 83+/-33 ms after shock and reinitiated ventricular fibrillation. Similar
      patterns of activation, including a quiescent period, were observed after shock
      was applied on the T wave of the paced beat that induced ventricular
      fibrillation. Upper limit of vulnerability correlated well with DFT50.
      CONCLUSIONS: In isolated swine right ventricles, an optical equivalent of an
      isoelectric window exists after near-threshold defibrillation shocks. These
      findings support the idea that a near-threshold defibrillation shock terminates
      all activation wavefronts but fails to halt ventricular fibrillation because the
      same shock reinitiates ventricular fibrillation after an isoelectric window.

PMID- 11447092
TI  - Successful ventricular defibrillation by the selective sodium-hydrogen exchanger
      isoform-1 inhibitor cariporide.
AB  - BACKGROUND: Sodium-hydrogen exchanger isoform-1 (NHE-1) activation worsens
      functional myocardial abnormalities associated with ischemia and reperfusion. We
      hypothesize that these abnormalities may limit cardiac resuscitation from
      ventricular fibrillation (VF) and investigated whether NHE-1 inhibition with the
      benzoylguanidine derivative cariporide could improve resuscitability,
      postresuscitation myocardial function, and short-term survival in isolated heart
      and intact rat models of VF. Methods and Results-- In the isolated rat heart, VF
      was induced for 25 minutes. Perfusion was interrupted for the initial 10 minutes
      and restarted at 10% of baseline flow for the remaining 15 minutes (simulating
      chest compression). Cariporide ameliorated ischemic contracture, prevented
      postresuscitation diastolic dysfunction, and favored earlier return of
      contractile function. In the intact rat, cariporide, injected into the right
      atrium before chest compression was started (after 6 minutes of untreated VF),
      prompted spontaneous defibrillation between minutes 7 and 9 of chest compression
      in 6 of 8 rats. In contrast, electrical defibrillation was required in each of 8
      control rats after completion of a predetermined 16-minute interval of VF. After
      resuscitation, cariporide-treated rats had less ventricular ectopic activity and
      normalized their hemodynamic function faster. Electrical defibrillation was then
      timed in control rats to match the time when spontaneous defibrillation occurred
      in cariporide-treated rats. With comparable VF duration, postresuscitation
      hemodynamic dysfunction was ameliorated by cariporide, but only when more severe
      ischemia was modeled by prolongation of the interval of untreated VF from 6 to 10
      minutes. CONCLUSION: NHE-1 inhibition may represent a novel and remarkably
      effective intervention for resuscitation from VF.

PMID- 11447093
TI  - Radiofrequency ablation of a posteroseptal accessory pathway associated with two
      diverticula of the coronary sinus.

PMID- 11447094
TI  - Hypereosinophilic syndrome and restrictive cardiomyopathy due to apical thrombi.

PMID- 11447095
TI  - Does amlodipine increase cancer incidence?

PMID- 11447096
TI  - Effect of cholesterol-lowering therapy on endothelial function.

PMID- 11447097
TI  - Niacin after coronary bypass grafting and for coronary disease prevention.

PMID- 11447098
TI  - Death rates versus deaths.

PMID- 11447099
TI  - Time relationships between plaque rupture and infarction.

PMID- 11447101
TI  - Apical-basal pattern formation in Arabidopsis embryogenesis.

PMID- 11447102
TI  - Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs.

PMID- 11447103
TI  - State transitions reveal the dynamics and flexibility of the photosynthetic
      apparatus.
AB  - The chloroplast-based photosynthetic apparatus of plants and algae associates
      various redox cofactors and pigments with approximately 70 polypeptides to form
      five major transmembrane protein complexes. Among these are two photosystems that
      have distinct light absorption properties but work in series to produce reducing
      equivalents aimed at the fixation of atmospheric carbon. A short term chromatic
      adaptation known as 'State transitions' was discovered thirty years ago that
      allows photosynthetic organisms to adapt to changes in light quality and
      intensity which would otherwise compromise the efficiency of photosynthetic
      energy conversion. A two-decade research effort has finally unraveled the major
      aspects of the molecular mechanism responsible for State transitions, and their
      physiological significance has been revisited. This review describes how a-still
      elusive-regulatory kinase senses the physiological state of the photosynthetic
      cell and triggers an extensive supramolecular reorganization of the
      photosynthetic membranes. The resulting picture of the photosynthetic apparatus
      is that of a highly flexible energy convertor that adapts to the ever-changing
      intracellular demand for ATP and/or reducing power.

PMID- 11447104
TI  - Intertwined structure of the DNA-binding domain of intron endonuclease I-TevI
      with its substrate.
AB  - I-TevI is a site-specific, sequence-tolerant intron endonuclease. The crystal
      structure of the DNA-binding domain of I-TevI complexed with the 20 bp primary
      binding region of its DNA target reveals an unusually extended structure composed
      of three subdomains: a Zn finger, an elongated segment containing a minor groove
      binding alpha-helix, and a helix-turn-helix. The protein wraps around the DNA,
      mostly following the minor groove, contacting the phosphate backbone along the
      full length of the duplex. Surprisingly, while the minor groove-binding helix and
      the helix-turn- helix subdomain make hydrophobic contacts, the few base-specific
      hydrogen bonds occur in segments that lack secondary structure and flank the
      intron insertion site. The multiple base-specific interactions over a long
      segment of the substrate are consistent with the observed high site specificity
      in spite of sequence tolerance, while the modular composition of the domain is
      pertinent to the evolution of homing endonucleases.

PMID- 11447105
TI  - The interaction of insulin-like growth factor-I with the N-terminal domain of
      IGFBP-5.
AB  - Insulin-like growth factors (IGFs) are key regulators of cell proliferation,
      differentiation and transformation, and are thus pivotal in cancer, especially
      breast, prostate and colon neoplasms. They are also important in many
      neurological and bone disorders. Their potent mitogenic and anti-apoptotic
      actions depend primarily on their availability to bind to the cell surface IGF-I
      receptor. In circulation and interstitial fluids, IGFs are largely unavailable as
      they are tightly associated with IGF-binding proteins (IGFBPs) and are released
      after IGFBP proteolysis. Here we report the 2.1 A crystal structure of the
      complex of IGF-I bound to the N-terminal IGF-binding domain of IGFBP-5 (mini
      IGFBP-5), a prototype interaction for all N-terminal domains of the IGFBP family.
      The principal interactions in the complex comprise interlaced hydrophobic side
      chains that protrude from both IGF-I and the IGFBP-5 fragment and a surrounding
      network of polar interactions. A solvent-exposed hydrophobic patch is located on
      the IGF-I pole opposite to the mini-IGFBP-5 binding region and marks the IGF-I
      receptor binding site.

PMID- 11447106
TI  - Crystal structure of the M-fragment of alpha-catenin: implications for modulation
      of cell adhesion.
AB  - The cytoskeletal protein alpha-catenin, which shares structural similarity with
      vinculin, is required for cadherin-mediated cell adhesion, and functions to
      modulate cell adhesive strength and to link the cadherins to the actin-based
      cytoskeleton. Here we describe the crystal structure of a region of alpha-catenin
      (residues 377-633) termed the M-fragment. The M-fragment is composed of a tandem
      repeat of two antiparallel four-helix bundles of virtually identical
      architectures that are related in structure to the dimerization domain of alpha
      catenin and the tail region of vinculin. These results suggest that alpha-catenin
      is composed of repeating antiparallel helical domains. The region of alpha
      catenin previously defined as an adhesion modulation domain corresponds to the C
      terminal four-helix bundle of the M-fragment, and in the crystal lattice these
      domains exist as dimers. Evidence for dimerization of the M-fragment of alpha
      catenin in solution was detected by chemical cross-linking experiments. The
      tendency of the adhesion modulation domain to form dimers may explain its
      biological activity of promoting cell-cell adhesiveness by inducing lateral
      dimerization of the associated cadherin molecule.

PMID- 11447107
TI  - Disruption of mannose activation in Leishmania mexicana: GDP-mannose
      pyrophosphorylase is required for virulence, but not for viability.
AB  - In eukaryotes, the enzyme GDP-mannose pyrophosphorylase (GDPMP) is essential for
      the formation of GDP-mannose, the central activated mannose donor in
      glycosylation reactions. Deletion of its gene is lethal in fungi, most likely as
      a consequence of disrupted glycoconjugate biosynthesis. Furthermore, absence of
      GDPMP enzyme activity and the expected loss of all mannose-containing
      glycoconjugates have so far not been observed in any eukaryotic organism. In this
      study we have cloned and characterized the gene encoding GDPMP from the
      eukaryotic protozoan parasite Leishmania mexicana. We report the generation of
      GDPMP gene deletion mutants of this human pathogen that are devoid of detectable
      GDPMP activity and completely lack mannose-containing glycoproteins and
      glycolipids, such as lipophosphoglycan, proteophosphoglycans,
      glycosylphosphatidylinositol protein membrane anchors, glycoinositolphospholipids
      and N-glycans. The loss of GDPMP renders the parasites unable to infect
      macrophages or mice, while gene addback restores virulence. Our study
      demonstrates that GDP-mannose biosynthesis is not essential for Leishmania
      viability in culture, but constitutes a virulence pathway in these human
      pathogens.

PMID- 11447108
TI  - Adenylyl cyclase Rv1625c of Mycobacterium tuberculosis: a progenitor of mammalian
      adenylyl cyclases.
AB  - The gene Rv1625c from Mycobacterium tuberculosis encodes a membrane-anchored
      adenylyl cyclase corresponding to exactly one-half of a mammalian adenylyl
      cyclase. An engineered, soluble form of Rv1625c was expressed in Escherichia
      coli. It formed a homodimeric cyclase with two catalytic centers. Amino acid
      mutations predicted to affect catalysis resulted in inactive monomers. A single
      catalytic center with wild-type activity could be reconstituted from mutated
      monomers in stringent analogy to the mammalian heterodimeric cyclase structure.
      The proposed existence of supramolecular adenylyl cyclase complexes was
      established by reconstitution from peptide-linked, mutation-inactivated
      homodimers resulting in pseudo-trimeric and -tetrameric complexes. The
      mycobacterial holoenzyme was expressed successfully in E.coli and mammalian
      HEK293 cells, i.e. its membrane targeting sequence was compatible with the
      bacterial and eukaryotic machinery for processing and membrane insertion. The
      membrane-anchored mycobacterial cyclase expressed in E.coli was purified to
      homogeneity as a first step toward the complete structural elucidation of this
      important protein. As the closest progenitor of the mammalian adenylyl cyclase
      family to date, the mycobacterial cyclase probably was spread by horizontal gene
      transfer.

PMID- 11447109
TI  - Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin
      mediated endocytosis.
AB  - Myosin VI is involved in membrane traffic and dynamics and is the only myosin
      known to move towards the minus end of actin filaments. Splice variants of myosin
      VI with a large insert in the tail domain were specifically expressed in
      polarized cells containing microvilli. In these polarized cells, endogenous
      myosin VI containing the large insert was concentrated at the apical domain co
      localizing with clathrin- coated pits/vesicles. Using full-length myosin VI and
      deletion mutants tagged with green fluorescent protein (GFP) we have shown that
      myosin VI associates and co-localizes with clathrin-coated pits/vesicles by its C
      terminal tail. Myosin VI, precipitated from whole cytosol, was present in a
      protein complex containing adaptor protein (AP)-2 and clathrin, and enriched in
      purified clathrin-coated vesicles. Over-expression of the tail domain of myosin
      VI containing the large insert in fibroblasts reduced transferrin uptake in
      transiently and stably transfected cells by >50%. Myosin VI is the first motor
      protein to be identified associated with clathrin-coated pits/vesicles and shown
      to modulate clathrin-mediated endocytosis.

PMID- 11447110
TI  - Importin 13: a novel mediator of nuclear import and export.
AB  - Importin beta-related receptors mediate translocation through nuclear pore
      complexes. Co-operation with the RanGTPase system allows them to bind and
      subsequently release their substrates on opposite sides of the nuclear envelope,
      which in turn ensures a directed nucleocytoplasmic transport. Here we identify a
      novel family member from higher eukaryotes that functions primarily, but not
      exclusively, in import. It accounts for nuclear accumulation of the SUMO
      1/sentrin-conjugating enzyme hUBC9 and mediates import of the RBM8 (Y14) protein,
      and is therefore referred to as importin 13 (Imp13). Unexpectedly, Imp13 also
      shows export activity towards the translation initiation factor eIF1A and is thus
      a case where a single importin beta-like receptor transports different substrates
      in opposite directions. However, Imp13 operates differently from typical
      exportins in that the binding of eIF1A to Imp13 is only regulated indirectly by
      RanGTP, and the cytoplasmic release of eIF1A from Imp13 is triggered by the
      loading of import substrates onto Imp13.

PMID- 11447111
TI  - A nuclear AAA-type ATPase (Rix7p) is required for biogenesis and nuclear export
      of 60S ribosomal subunits.
AB  - Ribosomal precursor particles are assembled in the nucleolus before export into
      the cytoplasm. Using a visual assay for nuclear accumulation of 60S subunits, we
      have isolated several conditional-lethal strains with defects in ribosomal export
      (rix mutants). Here we report the characterization of a mutation in an essential
      gene, RIX7, which encodes a novel member of the AAA ATPase superfamily. The rix7
      1 temperature-sensitive allele carries a point mutation that causes defects in
      pre-rRNA processing, biogenesis of 60S ribosomal subunits, and their subsequent
      export into the cytoplasm. Rix7p, which associates with 60S ribosomal precursor
      particles, localizes throughout the nucleus in exponentially growing cells, but
      concentrates in the nucleolus in stationary phase cells. When cells resume growth
      upon shift to fresh medium, Rix7p-green fluorescent protein exhibits a transient
      perinuclear location. We propose that a nuclear AAA ATPase is required for
      restructuring nucleoplasmic 60S pre-ribosomal particles to make them competent
      for nuclear export.

PMID- 11447112
TI  - Recruitment of cortexillin into the cleavage furrow is controlled by Rac1 and
      IQGAP-related proteins.
AB  - Cytokinesis in eukaryotic organisms is under the control of small GTP-binding
      proteins, although the underlying molecular mechanisms are not fully understood.
      Cortexillins are actin-binding proteins whose activity is crucial for cytokinesis
      in Dictyostelium. Here we show that the IQGAP-related and Rac1-binding protein
      DGAP1 specifically interacts with the C-terminal, actin-bundling domain of
      cortexillin I. Like cortexillin I, DGAP1 is enriched in the cortex of interphase
      cells and translocates to the cleavage furrow during cytokinesis. The activated
      form of the small GTPase Rac1A recruits DGAP1 into a quaternary complex with
      cortexillin I and II. In DGAP1(-) mutants, a complex can still be formed with a
      second IQGAP-related protein, GAPA. The simultaneous elimination of DGAP1 and
      GAPA, however, prevents complex formation and localization of the cortexillins to
      the cleavage furrow. This leads to a severe defect in cytokinesis, which is
      similar to that found in cortexillin I/II double-null mutants. Our observations
      define a novel and functionally significant signaling pathway that is required
      for cytokinesis.

PMID- 11447113
TI  - Positive and negative regulation of Raf kinase activity and function by
      phosphorylation.
AB  - Activating and inhibitory phosphorylation mechanisms play an essential role in
      regulating Raf kinase activity. Here we demonstrate that phosphorylation of C-Raf
      in the kinase activation loop (residues T491 and S494) is necessary, but not
      sufficient, for activation. C-Raf has additional activating phosphorylation sites
      at S338 and Y341. Mutating all four of these residues to acidic residues,
      S338D/Y341D/T491E/S494D (DDED), in C-Raf results in constitutive activity.
      However, acidic residue substitutions at the corresponding activation loop sites
      in B-Raf are sufficient to confer constitutive activity. B-Raf and C-Raf also
      utilize similar inhibitory phosphorylation mechanisms to regulate kinase
      activity. B-Raf has multiple inhibitory phosphorylation sites necessary for full
      kinase inhibition where C-Raf requires only one. We examined the functional
      significance of these inhibitory and activating phosphorylations in
      Caenorhabditis elegans lin-45 Raf. Eliminating the inhibitory phosphorylation or
      mimicking activating phosphorylation sites is sufficient to confer constitutive
      activity upon lin-45 Raf and induce multi-vulva phenotypes in C.elegans. Our
      results demonstrate that different members of the Raf family kinases have both
      common and distinct phosphorylation mechanisms to regulate kinase activity and
      biological function.

PMID- 11447114
TI  - Heterologous dimerization domains functionally substitute for the double-stranded
      RNA binding domains of the kinase PKR.
AB  - The protein kinase PKR (dsRNA-dependent protein kinase) phosphorylates the
      eukaryotic translation initiation factor eIF2alpha to downregulate protein
      synthesis in virus-infected cells. Two double-stranded RNA binding domains
      (dsRBDs) in the N-terminal half of PKR are thought to bind the activator double
      stranded RNA, mediate dimerization of the protein and target PKR to the ribosome.
      To investigate further the importance of dimerization for PKR activity, fusion
      proteins were generated linking the PKR kinase domain to heterologous
      dimerization domains. Whereas the isolated PKR kinase domain (KD) was non
      functional in vivo, expression of a glutathione S-transferase-KD fusion, or co
      expression of KD fusions containing the heterodimerization domains of the Xlim-1
      and Ldb1 proteins, restored PKR activity in yeast cells. Finally, coumermycin
      mediated dimerization of a GyrB-KD fusion protein increased eIF2alpha
      phosphorylation and inhibited reporter gene translation in mammalian cells. These
      results demonstrate the critical importance of dimerization for PKR activity in
      vivo, and suggest that a primary function of double-stranded RNA binding to the
      dsRBDs of native PKR is to promote dimerization and activation of the kinase
      domain.

PMID- 11447115
TI  - The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion
      molecule (JAM).
AB  - The establishment and maintenance of cellular polarity are critical for the
      development of multicellular organisms. PAR (partitioning-defective) proteins
      were identified in Caenorhabditis elegans as determinants of asymmetric cell
      division and polarized cell growth. Recently, vertebrate orthologues of two of
      these proteins, ASIP/PAR-3 and PAR-6, were found to form a signalling complex
      with the small GTPases Cdc42/Rac1 and with atypical protein kinase C (PKC). Here
      we show that ASIP/PAR-3 associates with the tight-junction-associated protein
      junctional adhesion molecule (JAM) in vitro and in vivo. No binding was observed
      with claudin-1, -4 or -5. In fibroblasts and CHO cells overexpressing JAM,
      endogenous ASIP is recruited to JAM at sites of cell-cell contact. Over
      expression of truncated JAM lacking the extracellular part disrupts ASIP/PAR-3
      localization at intercellular junctions and delays ASIP/PAR-3 recruitment to
      newly formed cell junctions. During junction formation, JAM appears early in
      primordial forms of junctions. Our data suggest that the ASIP/PAR-3-aPKC complex
      is tethered to tight junctions via its association with JAM, indicating a
      potential role for JAM in the generation of cell polarity in epithelial cells.

PMID- 11447116
TI  - T-loop phosphorylation stabilizes the CDK7-cyclin H-MAT1 complex in vivo and
      regulates its CTD kinase activity.
AB  - Cyclin-dependent kinase (CDK)7-cyclin H, the CDK-activating kinase (CAK) and
      TFIIH-associated kinase in metazoans can be activated in vitro through T-loop
      phosphorylation or binding to the RING finger protein MAT1. Although the two
      mechanisms can operate independently, we show that in a physiological setting,
      MAT1 binding and T-loop phosphorylation cooperate to stabilize the CAK complex of
      Drosophila. CDK7 forms a stable complex with cyclin H and MAT1 in vivo only when
      phosphorylated on either one of two residues (Ser164 or Thr170) in its T-loop.
      Mutation of both phosphorylation sites causes temperature-dependent dissociation
      of CDK7 complexes and lethality. Furthermore, phosphorylation of Thr170 greatly
      stimulates the activity of the CDK7- cyclin H-MAT1 complex towards the C-terminal
      domain of RNA polymerase II without significantly affecting activity towards
      CDK2. Remarkably, the substrate-specific increase in activity caused by T-loop
      phosphorylation is due entirely to accelerated enzyme turnover. Thus
      phosphorylation on Thr170 could provide a mechanism to augment CTD
      phosphorylation by TFIIH-associated CDK7, and thereby regulate transcription.

PMID- 11447117
TI  - Interleukin-10 targets p38 MAPK to modulate ARE-dependent TNF mRNA translation
      and limit intestinal pathology.
AB  - Interleukin-10 (IL-10) is a key inhibitory signal of inflammatory responses that
      regulates the production of potentially pathogenic cytokines like tumor necrosis
      factor (TNF). We show here that the development of chronic intestinal
      inflammation in IL-10-deficient mice requires the function of TNF, indicating
      that the IL-10/TNF axis regulates mucosal immunity. We further show that IL-10
      targets the 3' AU-rich elements (ARE) of TNF mRNA to inhibit its translation.
      Moreover, IL-10 does not alter TNF mRNA stability, and its action does not
      require the presence of the stability-regulating ARE binding factor
      tristetraprolin, indicating a differential assembly of stability and translation
      determinants on the TNF ARE. Inhibition of TNF translation by IL-10 is exerted
      mainly by inhibition of the activating p38/MAPK-activated protein kinase-2
      pathway. These results demonstrate a physiologically significant cross-talk
      between the IL-10 receptor and the stress-activated protein kinase modules
      targeting TNF mRNA translation. This cross-talk is necessary for optimal TNF
      production and for the maintenance of immune homeostasis in the gut.

PMID- 11447118
TI  - The Hsp90 chaperone complex is both a facilitator and a repressor of the dsRNA
      dependent kinase PKR.
AB  - PKR, a member of the eukaryotic initiation-factor 2alpha (eIF-2alpha) kinase
      family, mediates the host antiviral response and is implicated in tumor
      suppression and apoptosis. Here we show that PKR is regulated by the heat shock
      protein 90 (Hsp90) molecular chaperone complex. Mammalian PKR expressed in
      budding yeast depends on several components of the Hsp90 complex for accumulation
      and activity. In mammalian cells, inhibition of Hsp90 function with geldanamycin
      (GA) during de novo synthesis of PKR also interferes with its accumulation and
      activity. Hsp90 and its co-chaperone p23 bind to PKR through its N-terminal
      double-stranded (ds) RNA binding region as well as through its kinase domain.
      Both dsRNA and GA induce the rapid dissociation of Hsp90 and p23 from mature PKR,
      activate PKR both in vivo and in vitro and within minutes trigger the
      phosphorylation of the PKR substrate eIF-2alpha. A short-term exposure of cells
      to the Hsp90 inhibitors GA or radicicol not only derepresses PKR, but also
      activates the Raf-MAPK pathway. This suggests that the Hsp90 complex may more
      generally assist the regulatory domains of kinases and other Hsp90 substrates.

PMID- 11447119
TI  - Acf1, the largest subunit of CHRAC, regulates ISWI-induced nucleosome
      remodelling.
AB  - The chromatin accessibility complex (CHRAC) was originally defined biochemically
      as an ATP-dependent 'nucleosome remodelling' activity. Central to its activity is
      the ATPase ISWI, which catalyses the transfer of histone octamers between DNA
      segments in cis. In addition to ISWI, four other potential subunits were observed
      consistently in active CHRAC fractions. We have now identified the p175 subunit
      of CHRAC as Acf1, a protein known to associate with ISWI in the ACF complex.
      Interaction of Acf1 with ISWI enhances the efficiency of nucleosome sliding by an
      order of magnitude. Remarkably, it also modulates the nucleosome remodelling
      activity of ISWI qualitatively by altering the directionality of nucleosome
      movements and the histone 'tail' requirements of the reaction. The Acf1-ISWI
      heteromer tightly interacts with the two recently identified small histone fold
      proteins CHRAC-14 and CHRAC-16. Whether topoisomerase II is an integral subunit
      has been controversial. Refined analyses now suggest that topoisomerase II should
      not be considered a stable subunit of CHRAC. Accordingly, CHRAC can be
      molecularly defined as a complex consisting of ISWI, Acf1, CHRAC-14 and CHRAC-16.

PMID- 11447120
TI  - Crystal structure of an activated form of the PTS regulation domain from the LicT
      transcriptional antiterminator.
AB  - The transcriptional antiterminator protein LicT regulates the expression of
      Bacillus subtilis operons involved in beta-glucoside metabolism. It belongs to a
      newly characterized family of bacterial regulators whose activity is controlled
      by the phosphoenolpyruvate:sugar phosphotransferase system (PTS). LicT contains
      an N-terminal RNA-binding domain (56 residues), and a PTS regulation domain (PRD,
      221 residues) that is phosphorylated on conserved histidines in response to
      substrate availability. Replacement of both His207 and His269 with a negatively
      charged residue (aspartic acid) led to a highly active LicT variant that no
      longer responds to either induction or catabolite repression signals from the
      PTS. In contrast to wild type, the activated mutant form of the LicT regulatory
      domain crystallized easily and provided the first structure of a PRD, determined
      at 1.55 A resolution. The structure is a homodimer, each monomer containing two
      analogous alpha-helical domains. The phosphorylation sites are totally buried at
      the dimer interface and hence inaccessible to phosphorylating partners. The
      structure suggests important tertiary and quaternary rearrangements upon LicT
      activation, which could be communicated from the protein C-terminal end up to the
      RNA-binding domain.

PMID- 11447121
TI  - Phosphorylation of serine 230 promotes inducible transcriptional activity of heat
      shock factor 1.
AB  - Heat shock factor 1 (HSF1) is a serine-rich constitutively phosphorylated
      mediator of the stress response. Upon stress, HSF1 forms DNA-binding trimers,
      relocalizes to nuclear granules, undergoes inducible phosphorylation and acquires
      the properties of a transactivator. HSF1 is phosphorylated on multiple sites, but
      the sites and their function have remained an enigma. Here, we have analyzed
      sites of endogenous phosphorylation on human HSF1 and developed a phosphopeptide
      antibody to identify Ser230 as a novel in vivo phosphorylation site. Ser230 is
      located in the regulatory domain of HSF1, and promotes the magnitude of the
      inducible transcriptional activity. Ser230 lies within a consensus site for
      calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII
      overexpression enhances both the level of in vivo Ser230 phosphorylation and
      transactivation of HSF1. The importance of Ser230 was further established by the
      S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1
      when expressed in hsf1(-/-) cells. Our study provides the first evidence that
      phosphorylation is essential for the transcriptional activity of HSF1, and hence
      for induction of the heat shock response.

PMID- 11447122
TI  - Ribosomal protein S4 is a transcription factor with properties remarkably similar
      to NusA, a protein involved in both non-ribosomal and ribosomal RNA
      antitermination.
AB  - Escherichia coli ribosomal RNA (rRNA) operons contain antitermination motifs
      necessary for forming terminator-resistant transcription complexes. In
      preliminary work, we isolated 'antiterminating' transcription complexes and
      identified four new proteins potentially involved in rRNA transcription
      antitermination: ribosomal (r-) proteins S4, L3, L4 and L13. We show here that
      these r-proteins and Nus factors lead to an 11-fold increase in terminator read
      through in in vitro transcription reactions. A significant portion of the effect
      was a result of r-protein S4. We show that S4 acted as a general antitermination
      factor, with properties very similar to NusA. It retarded termination and
      increased read-through at Rho-dependent terminators, even in the absence of the
      rRNA antiterminator motif. High concentrations of NusG showed reduced
      antitermination by S4. Like rrn antitermination, S4 selectively antiterminated at
      Rho-dependent terminators. Lastly, S4 tightly bound RNA polymerase in vivo. Our
      results suggest that, like NusA, S4 is a general transcription antitermination
      factor that associates with RNA polymerase during normal transcription and is
      also involved in rRNA operon antitermination. A model for key r-proteins playing
      a regulatory role in rRNA synthesis is presented.

PMID- 11447123
TI  - The RNA binding protein YB-1 binds A/C-rich exon enhancers and stimulates
      splicing of the CD44 alternative exon v4.
AB  - Exon enhancers are accessory pre-mRNA splicing signals that stimulate exon
      splicing. One class of proteins, the serine-arginine-rich (SR) proteins, have
      been demonstrated to bind enhancers and activate splicing. Here we report that
      A/C-rich exon enhancers (ACE elements) are recognized by the human YB-1 protein,
      a non-SR protein. Sequence-specific binding of YB-1 was observed both to an ACE
      derived from an in vivo iterative selection protocol and to ACE elements in an
      alternative exon (v4) from the human CD44 gene. The ACE element that was the
      predominant YB-1 binding site in CD44 exon v4 was required for maximal in vivo
      splicing and in vitro spliceosome assembly. Expression of wild-type YB-1
      increased inclusion of exon v4, whereas a truncated form of YB-1 did not.
      Stimulation of exon v4 inclusion by wild-type YB-1 required the ACE necessary for
      YB-1 binding in vitro, suggesting that YB-1 stimulated exon inclusion in vivo by
      binding to an exonic ACE element. These observations identify a protein in
      addition to SR proteins that participates in the recognition of exon enhancers.

PMID- 11447124
TI  - The exosome of Trypanosoma brucei.
AB  - The yeast exosome is a complex of at least 10 essential 3'-5' riboexonucleases
      which is involved in 3'-processing of many RNA species. An exosome-like complex
      has been found or predicted to exist in other eukaryotes but not in Escherichia
      coli. The unicellular parasite Trypanosoma brucei diverged very early in
      eukaryotic evolution. We show here that T.brucei contains at least eight exosome
      subunit homologs, but only a subset of these associate in a complex. Accordingly,
      the T.brucei exosome is smaller than that of yeast. Both free and complex
      associated homologs are essential for cell viability and are involved in 5.8S
      rRNA maturation. We suggest that the exosome was present in primitive eukaryotes,
      and became increasingly complex during subsequent evolution.

PMID- 11447125
TI  - Synthesis of a novel hepatitis C virus protein by ribosomal frameshift.
AB  - Hepatitis C virus (HCV) is an important human pathogen that affects approximately
      100 million people worldwide. Its RNA genome codes for a polyprotein, which is
      cleaved by viral and cellular proteases to produce at least 10 mature viral
      protein products. We report here the discovery of a novel HCV protein synthesized
      by ribosomal frameshift. This protein, which we named the F protein, is
      synthesized from the initiation codon of the polyprotein sequence followed by
      ribosomal frameshift into the -2/+1 reading frame. This ribosomal frameshift
      requires only codons 8-14 of the core protein-coding sequence, and the shift
      junction is located at or near codon 11. An F protein analog synthesized in vitro
      reacted with the sera of HCV patients but not with the sera of hepatitis B
      patients, indicating the expression of the F protein during natural HCV
      infection. This unexpected finding may open new avenues for the development of
      anti-HCV drugs.

PMID- 11447126
TI  - Two overlapping reading frames in a single exon encode interacting proteins--a
      novel way of gene usage.
AB  - The >1 kb XL-exon of the rat XLalphas/Galphas gene encodes the 37 kDa XL-domain,
      the N-terminal half of the 78 kDa neuroendocrine-specific G-protein alpha-subunit
      XLalphas. Here, we describe a novel feature of the XL-exon, the presence of an
      alternative >1 kb open reading frame (ORF) that completely overlaps with the ORF
      encoding the XL-domain. The alternative ORF starts 32 nucleotides downstream of
      the start codon for the XL-domain and is terminated by a stop codon exactly at
      the end of the XL-exon. The alternative ORF encodes ALEX, a very basic (pI 11.8),
      proline-rich protein of 356 amino acids. Both XLalphas and ALEX are translated
      from the same mRNA. Like XLalphas, ALEX is expressed in neuroendocrine cells and
      tightly associated with the cytoplasmic leaflet of the plasma membrane.
      Remarkably, ALEX binds to the XL-domain of XLalphas. Our results reveal a
      mechanism of gene usage that is without precedent in mammalian genomes.

PMID- 11447127
TI  - Characterization of homologous recombination induced by replication inhibition in
      mammalian cells.
AB  - To analyze relationships between replication and homologous recombination in
      mammalian cells, we used replication inhibitors to treat mouse and hamster cell
      lines containing tandem repeat recombination substrates. In the first step, few
      double-strand breaks (DSBs) are produced, recombination is slightly increased,
      but cell lines defective in non-homologous end-joining (NHEJ) affected in ku86
      (xrs6) or xrcc4 (XR-1) genes show enhanced sensitivity to replication inhibitors.
      In the second step, replication inhibition leads to coordinated kinetics of DSB
      accumulation, Rad51 foci formation and RAD51-dependent gene conversion
      stimulation. In xrs6 as well as XR-1 cell lines, Rad51 foci accumulate more
      rapidly compared with their respective controls. We propose that replication
      inhibition produces DSBs, which are first processed by the NHEJ; then, following
      DSB accumulation, RAD51 recombination can act.

PMID- 11447128
TI  - A novel meiosis-specific protein of fission yeast, Meu13p, promotes homologous
      pairing independently of homologous recombination.
AB  - Meiotic homologous pairing is crucial to proper homologous recombination, which
      secures subsequent reductional chromosome segregation. We have identified a novel
      meiosis-specific protein of fission yeast Schizosaccharomyces pombe, Meu13p, to
      be a molecule that is required for proper homologous pairing and recombination.
      Rec12p (homologue of Saccharomyces cerevisiae Spo11p), which is essential for the
      initiation of meiotic recombination, is also shown for the first time to
      participate in the pairing process of S.pombe. Meu13p, however, contributes to
      pairing through a recombination-independent mechanism, as disruption of the
      meu13(+) gene reduces pairing whether the rec12(+) gene is deleted or not. We
      also demonstrate a dynamic nature of homologous pairing in living meiotic cells,
      which is markedly affected by meu13 deletion. Meu13p is not required for telomere
      clustering and the nuclear movement process, which are well known requirements
      for efficient pairing in S.pombe. Based on these results, together with the
      localization of Meu13p on meiotic chromatin, we propose that Meu13p directly
      promotes proper homologous pairing and recombination.

PMID- 11447129
TI  - Protein-DNA contacts and conformational changes in the Tn10 transpososome during
      assembly and activation for cleavage.
AB  - IHF or supercoiling is required early in Tn10 transposition, but at later stages
      they inhibit the reaction in a classic homeostatic loop. We investigated the
      mechanism of transpososome assembly and regulation using hydroxyl radical DNA
      protection and interference. We present a three-dimensional molecular model for
      the IHF-bent end of Tn10 wrapped around a transposase core. Contacts span some 80
      bp at the transposon end, but after assembly of an active complex containing
      metal ion, most contacts become dispensable. These include transposase contacts
      beyond the IHF site that chaperone assembly of the complex and are needed for
      efficient cleavage. Single and double-end breaks do not affect the complex but
      divalent metal ions promote large conformational changes at bp +1 and the
      flanking DNA.

PMID- 11447130
TI  - Epidermal growth factor receptor glycosylation is required for ganglioside GM3
      binding and GM3-mediated suppression [correction of suppresion] of activation.
AB  - Gangliosides are able to bind to the epidermal growth factor receptor and inhibit
      its activation, but the mechanism of this inhibition is unknown. To address the
      role of receptor carbohydrates in facilitating interaction with gangliosides, we
      examined the ability of GM3 to bind the deglycosylated receptor and inhibit its
      autophosphorylation. Flow cytometry studies demonstrated that deglycosylation of
      the receptor did not affect its ability to be transported to the cell membrane.
      In contrast with the native (fully glycosylated) receptor, GM3 did not
      coimmunoprecipitate with the deglycosylated receptor. Using a novel colorimetric
      bead binding assay, GM3 was shown to bind well to the immunoprecipitated native
      receptor but not at all to the deglycosylated receptor. Finally, the addition of
      GM3 to cells with deglycosylated epidermal growth factor receptors did not result
      in significant further inhibition of autophosphorylation of the receptor, despite
      a 10-fold decrease in phosphorylation of the native epidermal growth factor
      receptor by 200 microM GM3. These studies suggest that ganglioside affects
      epidermal growth factor receptor activity through a direct interaction that
      requires receptor glycosylation, and contribute to our understanding of the role
      of gangliosides in cell membrane function.

PMID- 11447131
TI  - Glycosylation analysis of two cysteine proteinase inhibitors from Atlantic salmon
      skin: di-O-acetylated sialic acids are the major sialic acid species on N
      glycans.
AB  - We have recently identified two novel cysteine proteinase inhibitors from the
      skin of Atlantic salmon (Salmo salar L.), named salmon kininogen and salarin. In
      preliminary experiments, the proteins were found to be both N- as well as O
      glycosylated. In the present study we show that both proteins carry biantennary
      alpha2,3-sialylated N-glycans. A very high amount of O-acetylated Neu5Ac units
      are present in the N-glycans, comprising about 60% di-O-acetylated species. Non-O
      acetylated Neu5Ac make up less than 5% of the sialic acids in the N-glycans. A
      small number of Neu5Acalpha2-8Neu5Ac structures were observed in the N-glycans as
      well. O-glycans from both proteins were recovered by reductive beta-elimination
      and were identified by mass spectrometric methods as mono- and disialylated core
      type 1 tri- and tetrasaccharides. The method used for O-glycan isolation
      prevented the identification of possible O-acetylation in the O-glycan-bound
      sialic acids, but O-acetylation was observed in one O-glycosylated peptide
      isolated from trypsin digest of salarin. The chemical nature of the sialic acid
      modifications was further studied by liquid chromatography tandem mass
      spectrometry of 1,2-diamino-4,5-methylenedioxybenzene-derivatized sialic acids,
      revealing 7-, 8-, and 9- but no 4-O-acetylation. To our knowledge, these are the
      first observations of sialic acid O-acetylation in N-glycans on fish species and
      represent clearly the most extensive N-glycan O-acetylation described on any
      species.

PMID- 11447132
TI  - Redirection of sialic acid metabolism in genetically engineered Escherichia coli.
AB  - Most microorganisms do not produce sialic acid (sialate), and those that do
      appear to use a biosynthetic mechanism distinct from mammals. Genetic hybrids of
      nonpathogenic, sialate-negative laboratory Escherichia coli K-12 strains designed
      for the de novo synthesis of the polysialic acid capsule from E. coli K1 proved
      useful in elucidating the genetics and biochemistry of capsule biosynthesis. In
      this article we propose a dynamic model of sialometabolism to investigate the
      effects of biosynthetic neu (N-acetylneuraminic acid) and catabolic nan (N
      acylneuraminate) mutations on the flux of intermediates through the sialate
      synthetic pathway. Intracellular sialate concentrations were determined by high
      pH anion exchange chromatography with pulsed amperometric detection. The results
      indicated that a strain carrying a null defect in the gene encoding
      polysialyltransferase (neuS) accumulated > 50 times more CMP-sialic acid than the
      wild type when strains were grown in a minimal medium supplemented with glucose
      and casamino acids. Metabolic accumulation of CMP-sialic acid depended on a
      functional sialic acid synthase (neuB), as shown by the inability of a strain
      lacking this enzyme to accumulate a detectable endogenous sialate pool. The neuB
      mutant concentrated trace sialate from the medium, indicating its potential value
      for quantitative analysis of free sialic acids in complex biological samples. The
      function of the sialate aldolase (encoded by nanA) in limiting intermediate flux
      through the synthetic pathway was determined by analyzing free sialate
      accumulation in neuA (CMP-sialic acid synthetase) nanA double mutants. The
      combined results demonstrate how E. coli avoids a futile cycle in which
      biosynthetic sialate induces the system for its own degradation and indicate the
      feasibility of generating sialooligosaccharide precursors through targeted
      manipulation of sialate metabolism.

PMID- 11447133
TI  - Toxoplasma gondii micronemal protein MIC1 is a lactose-binding lectin.
AB  - Host cell invasion by Toxoplasma gondii is a multistep process with one of the
      first steps being the apical release of micronemal proteins that interact with
      host receptors. We demonstrate here that micronemal protein 1 (MIC1) is a lactose
      binding lectin. MIC1 and MIC4 were recovered in the lactose-eluted (Lac(+))
      fraction on affinity chromatography on immobilized lactose of the soluble antigen
      fraction from tachyzoites of the virulent RH strain. MIC1 and MIC4 were both
      identified by N-terminal microsequencing. MIC4 was also identified by sequencing
      cDNA clones isolated from an expression library following screening with mouse
      polyclonal anti-60/70 kDa (Lac(+) proteins) serum. This antiserum localized the
      Lac(+) proteins on the apical region of T. gondii tachyzoites by confocal
      microscopy. The Lac(+) fraction induced hemagglutination (mainly type A human
      erythrocytes), which was inhibited by beta-galactosides (3 mM lactose and 12 mM
      galactose) but not by up to 100 mM melibiose (alpha-galactoside), fucose,
      mannose, or glucose or 0.2 mg/ml heparin. The lectin activity of the Lac(+)
      preparation was attributed to MIC1, because blotted MIC1, but not native MIC4,
      bound human erythrocyte type A and fetuin. The copurification of MIC1 and MIC4
      may have been due to their association, as reported by others. These data suggest
      that MIC1 may act through its lectin activity during T. gondii infection.

PMID- 11447134
TI  - Complete analysis of the glycosylation and disulfide bond pattern of human beta
      hexosaminidase B by MALDI-MS.
AB  - beta-hexosaminidase B is an enzyme that is involved in the degradation of
      glycolipids and glycans in the lysosome. Mutation in the HEXB gene lead to
      Sandhoff disease, a glycolipid storage disorder characterized by severe
      neurodegeneration. So far, little structural information on the protein is
      available. Here, the complete analysis of the disulfide bond pattern of the
      protein is described for the first time. Additionally, the structures of the N
      glycans are analyzed for the native human protein and for recombinant protein
      expressed in SF21 cells. For the analysis of the disulfide bond structure, the
      protein was proteolytically digested and the resulting peptides were analyzed by
      MALDI-MS. The analysis revealed three disulfide bonds (C91-C137; C309-C360; C534
      C551) and a free cysteine (C487). The analysis of the N-glycosylation was
      performed by tryptic digestion of the protein, isolation of glycopeptides by
      lectin chromatography and mass measurement before and after enzymatic
      deglycosylation. Carbohydrate structures were calculated from the mass difference
      between glycosylated and deglycosylated peptide. For beta-hexosaminidase B from
      human placenta, four N-glycans were identified and analyzed, whereas the
      recombinant protein expressed in SF21 cells carried only three glycans. In both
      cases the glycosylation belongs to the mannose-core- or high-mannose-type, and
      some carbohydrate structures are fucosylated.

PMID- 11447135
TI  - A rapid, semi-automated method for detection of Galbeta1-4GlcNAc alpha2,6
      sialyltransferase (EC 2.4.99.1) activity using the lectin Sambucus nigra
      agglutinin.
AB  - Sialyltransferase activity has traditionally been studied by determining the rate
      at which the enzyme transfers a labeled donor sugar to an acceptor substrate.
      These types of assays can be difficult to quantitate, and the separation of
      untransfered donor sugar from the sialylated acceptor is time-consuming. The
      biosensor-based method described here is both rapid and semi-automated. The NeuAc
      alpha2-6Gal-R-specific lectin Sambucus nigra agglutinin (SNA) immobilized to the
      carboxymethyl dextran surface of a BIAcore sensor chip was used to detect and
      measure the formation of the NeuAc-alpha2-6Gal-R moieties. The sialyltransferase
      assays were carried out using modified protocols based on the method described in
      Rearick, J.I., Sadler, J.E., Paulson, J.C., and Hill, R.L. (1979) Enzymatic
      characterization of betaD-galactoside alpha2-3 sialyltransferase from porcine
      submaxillary gland. J. Biol. Chem., 254, 4444-4451. The complete assay mixture
      was simply diluted before injection into the instrument. All injections were
      performed automatically using the robotics of the BIAcore instrument. Using this
      technique it is possible to detect product from 0.4 microU of commercial Galbeta1
      4GlcNAc alpha2,6-sialyltransferase (EC 2.4.99.1) (ST6Gal I). One unit of
      sialyltransferase is defined as the quantity that will transfer 1 micromol of N
      acetylneuraminic acid from cytidine monophosphate (CMP)-N-acetylneuraminic acid
      to asialofetuin per min at pH 6.5 and 37 degrees C. The method described here
      requires as little as 10 microl total assay volume, thus reducing the consumption
      of reagents. In addition, the sample is completely recoverable from the sensor
      chip surface, which allows for downstream analysis of the reaction product if
      desired. This method eliminates the need for labeled donor and acceptor molecules
      and does not require the separation of the substrates from the product before
      analysis. Although some kinetic properties of the enzyme can be estimated using
      this method, further development and validation is required. The method is most
      useful in determining qualitative estimates of ST6Gal I activity in tissue
      extracts and in characterizing the production of enzymes in cultured cell
      systems. The use of a microtiter plate assay format enables the rapid screening
      of multiple fractions for sialyltransferase activity.

PMID- 11447136
TI  - N-glycan structure of a short-lived variant of ribophorin I expressed in the
      MadIA214 glycosylation-defective cell line reveals the role of a mannosidase that
      is not ER mannosidase I in the process of glycoprotein degradation.
AB  - A soluble form of ribophorin I (RI(332)) is rapidly degraded in Hela and Chinese
      hamster ovary (CHO) cells by a cytosolic proteasomal pathway, and the N-linked
      glycan present on the protein may play an important role in this process.
      Specifically, it has been suggested that endoplasmic reticulum (ER) mannosidase I
      could trigger the targeting of improperly folded glycoproteins to degradation. We
      used a CHO-derived glycosylation-defective cell line, MadIA214, for investigating
      the role of mannosidase(s) as a signal for glycoprotein degradation.
      Glycoproteins in MadIA214 cells carry truncated Glc(1)Man(5)GlcNAc(2) N-glycans.
      This oligomannoside structure interferes with protein maturation and folding,
      leading to an alteration of the ER morphology and the detection of high levels of
      soluble oligomannoside species caused by glycoprotein degradation. An HA-epitope
      tagged soluble variant of ribophorin I (RI(332)-3HA) expressed in MadIA214 cells
      was rapidly degraded, comparable to control cells with the complete
      Glc(3)Man(9)GlcNAc(2) N-glycan. ER-associated degradation (ERAD) of RI(332)-3HA
      was also proteasome-mediated in MadIA214 cells, as demonstrated by inhibition of
      RI(332)-3HA degradation with agents specifically blocking proteasomal activities.
      Two inhibitors of alpha1,2-mannosidase activity also stabilized RI(332)-3HA in
      the glycosylation-defective cell line. This is striking, because the major
      mannosidase activity in the ER is the one of mannosidase I, specific for a
      mannose alpha1,2-linkage that is absent from the truncated Man(5) structure.
      Interestingly, though the Man(5) derivative was present in large amounts in the
      total protein pool, the two major species linked to RI(332)-3HA shortly after
      synthesis consisted of Glc(1)Man(5 )and Man(4), being replaced by Man(4 )and
      Man(3) when proteasomal degradation was inhibited. In contrast, the untrimmed
      intermediate of RI(332)-3HA was detected in mutant cells treated with mannosidase
      inhibitors. Our results unambiguously demonstrate that an alpha1,2-mannosidase
      that is not ER mannosidase I is involved in ERAD of RI(332-)3HA in the
      glycosylation-defective cell line, MadIA214.

PMID- 11447137
TI  - Synthesis of alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R) on human tumor
      cells by recombinant alpha1,3galactosyltransferase produced in Pichia pastoris.
AB  - This study describes the processing of human tumor cells or cell membranes to
      express alpha-gal epitopes (Galalpha1-3Gal-beta1-4GlcNAc-R) by the use of New
      World monkey (marmoset) recombinant alpha1,3galactosyltransferase (ralpha1,3GT),
      produced in the yeast Pichia pastoris. Such tumor cells and membranes may serve,
      in cancer patients, as autologous tumor vaccines that are targeted in vivo to
      antigen-presenting cells by the anti-Gal antibody. This ralpha1,3GT lacks
      transmembrane and cytoplasmic domains, ensuring its solubility without detergent.
      It is effectively produced in P. pastoris under constitutive expression of the
      P(GAP) promoter and is secreted into the culture medium in a soluble, truncated
      form fused to a (His)(6) tag. This tag enables the simple affinity purification
      of ralpha1,3GT on a nickel-Sepharose column and elution with imidazole. The
      purified enzyme appears in SDS-PAGE as two bands with the size of 40 and 41 kDa
      and displays the same acceptor specificity as the mammalian native enzyme.
      ralpha1,3GT is very effective in synthesizing alpha-gal epitopes on membrane
      bound carbohydrate chains and displays a specific activity of 1.2 nM membrane
      bound alpha-gal epitopes/min/mg. Incubation of very large amounts of human acute
      myeloid leukemia cells (1 x 10(9 )cells) with neuraminidase, ralpha1,3GT, and UDP
      Gal resulted in the synthesis of approximately 6 x 10(6 )alpha-gal epitopes per
      cell. Effective synthesis of alpha-gal epitopes could be achieved also with as
      much as 2 g cell membranes prepared from the tumor of a patient with ovarian
      carcinoma. These data imply that ralpha1,3GT produced in P. pastoris is suitable
      for the synthesis of alpha-gal epitopes on bulk amounts of tumor cells or cell
      membranes required for the preparation of autologous tumor vaccines.

PMID- 11447138
TI  - Cell surface-expressed Thomsen-Friedenreich antigen in colon cancer is
      predominantly carried on high molecular weight splice variants of CD44.
AB  - Increased mucosal expression of TF, the Thomsen-Friedenreich oncofetal blood
      group antigen (galactose beta1-3 N-acetylgalactosamine alpha-) occurs in colon
      cancer and colitis. This allows binding of TF-specific lectins, such as peanut
      agglutinin (PNA), which is mitogenic to the colorectal epithelium. To identify
      the cell surface TF-expressing glycoprotein(s), HT29 and Caco2 colon cancer cells
      were surface-labeled with Na[(125)I] and subjected to PNA-agarose affinity
      purification and electrophoresis. Proteins, approximately 110-180 kDa, present in
      HT29 but not Caco2 were identified by Western blotting as high molecular weight
      splice variants of CD44 (CD44v). Selective removal of TF antigen by Streptococcus
      pneumoniae endo-alpha-N-acetylgalactosaminidase substantially reduced PNA binding
      to CD44v. Immunoprecipitated CD44v from HT29 cell extracts also expressed sialyl
      Tn (sialyl 2-6 N-acetylgalactosaminealpha-). Incubation of PNA 15 microg/ml with
      HT29 cells caused no additional proliferative effect in the presence of anti
      CD44v6 mAb. In colon cancer tissue extracts (N = 3) PNA bound to CD44v but not to
      standard CD44. These data show that CD44v is a major PNA-binding glycoprotein in
      colon cancer cells. Because CD44 high molecular weight splice variants are
      present in colon cancer and inflammatory bowel disease tissue but are absent from
      normal mucosa, these results may also explain the increased PNA reactivity in
      colon cancer and inflammatory bowel disease. The coexpression of oncofetal
      carbohydrate antigens TF and sialyl-Tn on CD44 splice variants provides a link
      between cancer-associated changes in glycosylation and CD44 splicing, both of
      which correlate with increased metastatic potential.

PMID- 11447139
TI  - Expression of a membrane-bound form of Trypanosoma cruzi trans-sialidase in
      baculovirus-infected insect cells: a potential tool for sialylation of
      glycoproteins produced in the baculovirus-insect cells system.
AB  - A chimeric protein containing the catalytic domain of Trypanosoma cruzi trans
      sialidase, the transmembrane domain of the major envelope glycoprotein of the
      baculovirus (gp67), and the signal peptide of ecdysteroid glucosyltransferase of
      the baculovirus was expressed under the control of the very late promoter p10 in
      baculovirus-infected lepidopteran cells. The recombinant protein was found to be
      enzymatically active. Three days after infection, equal amounts of activity were
      found associated to the plasma membrane and in the infection medium, both forms
      having the same apparent molecular weight and being N-glycosylated. When
      exogenous galactosylated acceptors (lactose or asialo-alpha1-acid glycoprotein)
      were added in the culture medium of cells infected with the recombinant
      baculovirus in the presence of a sialylated donor, a sialylation could be
      observed. Therefore, we propose the use of trans-sialidase as a potential tool
      for sialylation of glycoconjugates in the baculovirus-insect cells system.

PMID- 11447140
TI  - The observation of multivalent complexes of Shiga-like toxin with globotriaoside
      and the determination of their stoichiometry by nanoelectrospray Fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - We show by nanoelectrospray ionization (nanoES) Fourier-transform ion cyclotron
      resonance mass spectrometry (FT-ICR MS) that it is possible to observe
      oligosaccharide-protein complexes with dissociation constants in the millimolar
      range, such as P(k) trisaccharide (globotriaoside) complexed with the Shiga-like
      toxin (SLT) of pathogenic E. coli. It is further demonstrated that nanoES/FT-ICR
      MS is an exquisite method to study quantitative aspects of the association of
      mono- and polyvalent oligosaccharide ligands with multimeric proteins, such as
      the SLTs. At increasing trisaccharide:protein ratios it was shown that the B(5
      )toxin subunit complexes with 5 P(k) trisaccharides and only after all 5 copies
      of site 2 are essentially filled do any of the remaining 10 receptor sites become
      occupied. From the distribution of bound P(k)'s at the five binding sites, it was
      possible to establish association constants for each of the five sites and to
      confirm that binding occurs noncooperatively, the association constants for each
      site are identical and that compared to site 1, site 2 exhibits a tenfold higher
      affinity for the globotriaoside synthetic ligand 1. The facile identification of
      the occupancy of binding sites represents information that is not readily
      available by other techniques. This sensitive and rapid estimation of association
      constants for protein-ligand complexes, which are free of unpredictable secondary
      effects that plague enzyme linked assays, is likely to find wide application.

PMID- 11447141
TI  - Dendritic cells: immune saviors or Achilles' heel?

PMID- 11447142
TI  - Malnutrition alters the innate immune response and increases early
      visceralization following Leishmania donovani infection.
AB  - Malnutrition is a risk factor for the development of visceral leishmaniasis.
      However, the immunological basis for this susceptibility is unknown. We have
      developed a mouse model to study the effect of malnutrition on innate immunity
      and early visceralization following Leishmania donovani infection. Three
      deficient diets were studied, including 6, 3, or 1% protein; these diets were
      also deficient in iron, zinc, and calories. The control diet contained 17%
      protein, was zinc and iron sufficient, and was provided ab libitum. Three days
      after infection with L. donovani promastigotes, the total extradermal (lymph
      nodes, liver, and spleen) and skin parasite burdens were equivalent in the
      malnourished (3% protein) and control mice, but in the malnourished group, a
      greater percentage (39.8 and 4.0%, respectively; P = 0.009) of the extradermal
      parasite burden was contained in the spleen and liver. The comparable levels of
      parasites in the footpads in the two diet groups and the higher lymph node
      parasite burdens in the well-nourished mice indicated that the higher visceral
      parasite burdens in the malnourished mice were not due to a deficit in local
      parasite killing but to a failure of lymph node barrier function. Lymph node
      cells from the malnourished, infected mice produced increased levels of
      prostaglandin E(2) (PGE(2)) and decreased levels of interleukin-10. Inducible
      nitric oxide synthase activity was significantly lower in the spleen and liver of
      the malnourished mice. Thus, malnutrition causes a failure of lymph node barrier
      function after L. donovani infection, which may be related to excessive
      production of PGE(2) and decreased levels of IL-10 and nitric oxide.

PMID- 11447143
TI  - Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not
      protective against experimental visceral leishmaniasis.
AB  - The acquisition of immunity following subclinical or resolved infection with the
      intracellular parasite Leishmania donovani suggests that vaccination could
      prevent visceral leishmaniasis (VL). The LACK (Leishmania homolog of receptors
      for activated C kinase) antigen is of interest as a vaccine candidate for the
      leishmaniases because of its immunopathogenic role in murine L. major infection.
      Immunization of mice with a truncated (24-kDa) version of the 36-kDa LACK
      antigen, delivered in either protein or DNA form, was found previously to protect
      against cutaneous L. major infection by redirecting the early T-cell response
      away from a pathogenic interleukin-4 (IL-4) response and toward a protective Th1
      response. The amino acid sequence of the Leishmania p36(LACK) antigen is highly
      conserved, but the efficacy of this vaccine antigen in preventing disease caused
      by strains other than L. major has not been determined. We investigated the
      efficacy of a p36(LACK) DNA vaccine against VL because of the serious nature of
      this form of leishmaniasis and because it was unclear whether the LACK vaccine
      would be effective in a model where there was not a dominant pathogenic IL-4
      response. We demonstrate here that although the LACK DNA vaccine induced a robust
      parasite-specific Th1 immune response (IFN-gamma but not IL-4 production) and
      primed for an in vivo T-cell response to inoculated parasites, it did not induce
      protection against cutaneous or systemic L. donovani challenge. Coadministration
      of IL-12 DNA with the vaccine did not enhance the strong vaccine-induced Th1
      response or augment a protective effect.

PMID- 11447144
TI  - Haemophilus ducreyi inhibits phagocytosis by U-937 cells, a human macrophage-like
      cell line.
AB  - Haemophilus ducreyi is a gram-negative obligate human pathogen that causes the
      genital ulcer disease chancroid. Chancroid lesions are deep necrotic ulcers with
      an immune cell infiltrate that includes macrophages. Despite the presence of
      these phagocytic cells, chancroid ulcers can persist for months and live H.
      ducreyi can be isolated from these lesions. To analyze the interaction of H.
      ducreyi with macrophages, we investigated the ability of H. ducreyi strain 35000
      to adhere to, invade, and survive within U-937 cells, a human macrophage-like
      cell line. We found that although H. ducreyi strain 35000 adhered efficiently to
      U-937 cells, few bacteria were internalized, suggesting that H. ducreyi avoids
      phagocytosis by human macrophages. The few bacteria that were phagocytosed in
      these experiments were rapidly killed. We also found that H. ducreyi inhibits the
      phagocytosis of a secondary target (opsonized sheep red blood cells).
      Antiphagocytic activity was found in logarithmic, stationary-phase, and plate
      grown cultures and was associated with whole, live bacteria but not with heat
      killed cultures, sonicates, or culture supernatants. Phagocytosis was
      significantly inhibited after a 15-min exposure to H. ducreyi, and a multiplicity
      of infection of approximately 1 CFU per macrophage was sufficient to cause a
      significant reduction in phagocytosis by U-937 cells. Finally, all of nine H.
      ducreyi strains tested were antiphagocytic, suggesting that this is a common
      virulence mechanism for this organism. This finding suggests a mechanism by which
      H. ducreyi avoids killing and clearance by macrophages in chancroid lesions and
      inguinal lymph nodes.

PMID- 11447145
TI  - Construction, genotypic and phenotypic characterization, and immunogenicity of
      attenuated DeltaguaBA Salmonella enterica serovar Typhi strain CVD 915.
AB  - A promising live attenuated typhoid vaccine candidate strain for mucosal
      immunization was developed by introducing a deletion in the guaBA locus of
      pathogenic Salmonella enterica serovar Typhi strain Ty2. The resultant DeltaguaBA
      mutant, serovar Typhi CVD 915, has a gene encoding resistance to arsenite
      replacing the deleted sequence within guaBA, thereby providing a marker to
      readily identify the vaccine strain. CVD 915 was compared in in vitro and in vivo
      assays with wild-type strain Ty2, licensed live oral typhoid vaccine strain
      Ty21a, or attenuated serovar Typhi vaccine strain CVD 908-htrA (harboring
      mutations in aroC, aroD, and htrA). CVD 915 was less invasive than CVD 908-htrA
      in tissue culture and was more crippled in its ability to proliferate after
      invasion. In mice inoculated intraperitoneally with serovar Typhi and hog gastric
      mucin (to estimate the relative degree of attenuation), the 50% lethal dose of
      CVD 915 (7.7 x 10(7) CFU) was significantly higher than that of wild-type Ty2
      (1.4 x 10(2) CFU) and was only slightly lower than that of Ty21a (1.9 x 10(8)
      CFU). Strong serum O and H antibody responses were recorded in mice inoculated
      intranasally with CVD 915, which were higher than those elicited by Ty21a and
      similar to those stimulated by CVD 908-htrA. CVD 915 also elicited potent
      proliferative responses in splenocytes from immunized mice stimulated with
      serovar Typhi antigens. Used as a live vector, CVD 915(pTETlpp) elicited high
      titers of serum immunoglobulin G anti-fragment C. These encouraging preclinical
      data pave the way for phase 1 clinical trials with CVD 915.

PMID- 11447146
TI  - Decreased amounts of cell wall-associated protein A and fibronectin-binding
      proteins in Staphylococcus aureus sarA mutants due to up-regulation of
      extracellular proteases.
AB  - Data have been presented indicating that Staphylococcus aureus cell surface
      protein can be degraded by extracellular proteases produced by the same
      bacterium. We have found that in sarA mutant cells, which produce high amounts of
      four major extracellular proteases (staphylococcal serine protease [V8 protease]
      [SspA], cysteine protease [SspB], aureolysin [metalloprotease] [Aur], and
      staphopain [Scp]), the levels of cell-bound fibronectin-binding proteins (FnBPs)
      and protein A were very low compared to those of wild-type cells, in spite of
      unaltered or increased transcription of the corresponding genes. Cultivation of
      sarA mutant cells in the presence of the global protease inhibitor alpha(2)
      macroglobulin resulted in a 16-fold increase in cell-bound FnBPs, indicating that
      extracellular proteases were responsible for the decreased amounts of FnBPs in
      sarA mutant cells. The protease inhibitor E64 had no effect on the level of
      FnBPs, indicating that cysteine proteases were not involved. Inactivation of
      either ssp or aur in the prototype S. aureus strain 8325-4 resulted in a
      threefold increase in the amount of cell-bound FnBPs. Inactivation of the same
      protease genes in a sarA mutant of 8325-4 resulted in a 10- to 20-fold increase
      in cell-bound protein A. As the serine protease requires aureolysin to be
      activated, it can thus be concluded that the serine protease is the most
      important protease in the release of cell-bound FnBPs and protein A.

PMID- 11447147
TI  - SarT, a repressor of alpha-hemolysin in Staphylococcus aureus.
AB  - In searching the Staphylococcus aureus genome, we found several homologs to SarA.
      One of these genes, sarT, codes for a basic protein with 118 residues and a
      predicted molecular size of 16,096 Da. Northern blot analysis revealed that the
      expression of sarT was repressed by sarA and agr. An insertion sarT mutant
      generated in S. aureus RN6390 and 8325-4 backgrounds revealed minimal effect on
      the expression of sarR and sarA. The RNAIII level was notably increased in the
      sarT mutant, particularly in postexponential-phase cells, while the augmentative
      effect on RNAII was less. SarT repressed the expression of alpha-hemolysin, as
      determined by Northern blotting, Western blotting, and a rabbit erythrocyte
      hemolytic assay. This repression was relieved upon complementation. Similar to
      agr and sarA mutants, which predictably displayed a reduction in hla expression,
      the agr sarT mutant exhibited a lower level of hla transcription than the sarT
      mutant. In contrast, hla transcription was enhanced in the sarA sarT mutant
      compared with the single sarA mutant. Collectively, these results indicated that
      the sarA locus, contrary to the regulatory action of agr, induced alpha-hemolysin
      production by repressing sarT, a repressor of hla transcription.

PMID- 11447148
TI  - Assessment of Helicobacter pylori gene expression within mouse and human gastric
      mucosae by real-time reverse transcriptase PCR.
AB  - Despite increasing knowledge on the biology of Helicobacter pylori, little is
      known about the expression pattern of its genome during infection. While mouse
      models of infection have been widely used for the screening of protective
      antigens, the reliability of the mouse model for gene expression analysis has not
      been assessed. In an attempt to address this question, we have developed a
      quantitative reverse transcriptase PCR (RT-PCR) that allowed the detection of
      minute amounts of mRNA within the gastric mucosa. The expression of four genes,
      16S rRNA, ureA (encoding urease A subunit), katA (catalase), and alpA (an
      adhesin), was monitored during the course of a 6-month infection of mice and in
      biopsy samples from of 15 infected humans. We found that the selected genes were
      all expressed within both mouse and human infected mucosae. Moreover, the
      relative abundance of transcripts was the same (16S rRNA > ureA > katA > alpA),
      in the two models. Finally, results obtained with the mouse model suggest a
      negative effect of bacterial burden on the number of transcripts of each gene
      expressed per CFU (P < 0.05 for 16S rRNA, alpA, and katA). Overall, this study
      demonstrates that real-time RT-PCR is a powerful tool for the detection and
      quantification of H. pylori gene expression within the gastric mucosa and
      strongly indicates that mice experimentally infected with H. pylori provide a
      valuable model for the analysis of bacterial gene expression during infection.

PMID- 11447149
TI  - Facilitated intranasal induction of mucosal and systemic immunity to mutans
      streptococcal glucosyltransferase peptide vaccines.
AB  - Synthetic peptide vaccines which are derived from functional domains of
      Streptococcus mutans glucosyltransferases (GTF) have been shown to induce
      protective immunity in Sprague-Dawley rats after subcutaneous injection in the
      salivary gland region. Since mucosal induction of salivary immunity would be
      preferable in humans, we explored methods to induce mucosal antibody in the rat
      to the GTF peptide vaccines HDS and HDS-GLU after intranasal administration.
      Several methods of facilitation of the immune response were studied: the
      incorporation of peptides in bioadhesive poly(D,L-lactide-coglycolide) (PLGA)
      microparticles, the use of monoepitopic (HDS) or diepitopic (HDS-GLU) peptide
      constructs, or the use of mucosal adjuvants. Salivary immunoglobulin A (IgA)
      responses were not detected after intranasal administration of diepitopic HDS-GLU
      peptide constructs in alum or after incorporation into PLGA microparticles.
      However, significant primary and secondary salivary IgA and serum IgG antibody
      responses to HDS were induced in all rats when cholera holotoxin (CT) or a
      detoxified mutant Escherichia coli heat-labile enterotoxin (R192G LT) were
      intranasally administered with HDS peptide constructs in PLGA. Coadministration
      of LT with HDS resulted in predominantly IgG2a responses in the serum, while
      coadministration with CT resulted in significant IgG1 and IgG2a responses to HDS.
      Serum IgG antibody, which was induced to the HDS peptide construct by
      coadministration with these adjuvants, also bound intact mutans streptococcal GTF
      in an enzyme-linked immunosorbent assay and inhibited its enzymatic activity.
      Thus, immune responses which are potentially protective for dental caries can be
      induced to peptide-based GTF vaccines after mucosal administration if combined
      with the CT or LT R192G mucosal adjuvant.

PMID- 11447150
TI  - Relationship of anti-Lewis x and anti-Lewis y antibodies in serum samples from
      gastric cancer and chronic gastritis patients to Helicobacter pylori-mediated
      autoimmunity.
AB  - Lewis (Le) antigens have been implicated in the pathogenesis of atrophic
      gastritis and gastric cancer in the setting of Helicobacter pylori infection, and
      H. pylori-induced anti-Le antibodies have been described that cross-react with
      the gastric mucosa of both mice and humans. The aim of this study was to examine
      the presence of anti-Le antibodies in patients with H. pylori infection and
      gastric cancer and to examine the relationships between anti-Le antibody
      production, bacterial Le expression, gastric histopathology, and host Le
      erythrocyte phenotype. Anti-Le antibody production and H. pylori Le expression
      were determined by enzyme-linked immunosorbent assay, erythrocyte Le phenotype
      was examined by agglutination assays, and histology was scored blindly.
      Significant levels of anti-Le(x) antibody (P < 0.0001, T = 76.4, DF = 5) and anti
      Le(y) antibody (P < 0.0001, T = 73.05, DF = 5) were found in the sera of patients
      with gastric cancer and other H. pylori-associated pathology compared with H.
      pylori-negative controls. Following incubation of patient sera with synthetic Le
      glycoconjugates, anti-Le(x) and -Le(y) autoantibody binding was abolished. The
      degree of the anti-Le(x) and -Le(y) antibody response was unrelated to the host
      Le phenotype but was significantly associated with the bacterial expression of
      Le(x) (r = 0.863, r(2) = 0.745, P < 0.0001) and Le(y) (r = 0.796, r(2) = 0.634, P
      < 0.0001), respectively. Collectively, these data suggest that anti-Le antibodies
      are present in most patients with H. pylori infection, including those with
      gastric cancer, that variability exists in the strength of the anti-Le response,
      and that this response is independent of the host Le phenotype but related to the
      bacterial Le phenotype.

PMID- 11447151
TI  - Potential virulence role of the Legionella pneumophila ptsP ortholog.
AB  - We previously identified the Legionella pneumophila ptsP (phosphoenolpyruvate
      phosphotransferase) ortholog gene as a putative virulence factor in a study of
      signature-tagged mutagenesis using a guinea pig pneumonia model. In this study,
      we further defined the phenotypic properties of L. pneumophila ptsP and its
      complete sequence. The L. pneumophila ptsP was 2,295 bases in length. Its deduced
      amino acid sequence had high similarity with ptsP orthologs of Pseudomonas
      aeruginosa, Azotobacter vinelandii, and Escherichia coli, with nearly identical
      lengths. Here we show that while the mutant grew well in laboratory media, it was
      defective in both lung and spleen multiplication in guinea pigs. It grew slowly
      in guinea pig alveolar macrophages despite good uptake into the cells.
      Furthermore, there was minimal growth in a human alveolar epithelial cell line
      (A549). Transcomplementation of the L. pneumophila ptsP mutant almost completely
      rescued its growth in alveolar macrophages, in A549 cells, and in guinea pig lung
      and spleen. The L. pneumophila ptsP mutant was capable of evasion of phagosome
      lysosome fusion and resided in ribosome-studded phagosomes. Pore formation
      activity of the mutant was normal. The L. pneumophila ptsP mutant expressed DotA
      and IcmX in apparently normal amounts, suggesting that the ptsP mutation did not
      affect dotA and icmX regulation. In addition, the mutant was resistant to serum
      and neutrophil killing. Taken together, these findings show that L. pneumophila
      ptsP is required for full in vivo virulence of L. pneumophila, most probably by
      affecting intracellular growth.

PMID- 11447152
TI  - In situ activation of helper T cells in the lung.
AB  - To better understand the lung and systemic responses of helper T cells mediating
      memory immunity to Mycobacterium tuberculosis, we used three- and four-color flow
      cytometry to study the surface phenotype of CD4(+) lymphocytes. Bronchoalveolar
      lavage (BAL) fluid and peripheral blood (PB) samples were obtained from a total
      of 25 subjects, including 10 tuberculosis (TB)-infected subjects, 8 purified
      protein-derivative-negative subjects, and 7 purified-protein-derivative-positive
      subjects. In marked contrast to CD4(+) lymphocytes from PB (9% +/- 5% expressing
      CD45RA and CD29), the majority (55% +/- 16%) of CD4(+) lymphocytes in BAL (ALs)
      simultaneously expressed CD45RA, a naive T-cell marker, and CD29, members of the
      very late activation family. Further evaluation revealed that CD4(+) ALs
      expressed both CD45RA and CD45RO, a memory T-cell marker. In addition, the
      proportion of CD4(+) lymphocytes expressing CD69, an early activation marker, was
      drastically increased in BAL fluid (83% +/- 9%) compared to PB (1% +/- 1%),
      whereas no significant difference was seen in the expression of CD25, the low
      affinity interleukin 2 receptor (34% +/- 15% versus 40% +/- 16%). More
      importantly, we identified a minor population of CD69(bright) CD25(bright) CD4(+)
      lymphocytes in BAL (10% +/- 6%) that were consistently absent from PB (1% +/-
      1%). Thus, CD4(+) lymphocytes in the lung paradoxically coexpress surface
      molecules characteristic of naive and memory helper T cells as well as surface
      molecules commonly associated with early and late stages of activation. No
      difference was observed for ALs obtained from TB-infected and uninfected lung
      segments in this regard. It remains to be determined if these surface molecules
      are induced by the alveolar environment or if CD4(+) lymphocytes coexpressing
      this unusual combination of surface molecules are selectively recruited from the
      circulation. Our data suggest that ex vivo experiments on helper T-cell subsets
      that display distinctive phenotypes may be pivotal to studies on the human immune
      response to potential TB vaccines.

PMID- 11447153
TI  - Conformational nature of the Borrelia burgdorferi decorin binding protein A
      epitopes that elicit protective antibodies.
AB  - Decorin binding protein A (DbpA) has been shown by several laboratories to be a
      protective antigen for the prevention of experimental Borrelia burgdorferi
      infection in the mouse model of Lyme borreliosis. However, different recombinant
      forms of the antigen having either lipidated amino termini, approximating the
      natural secretion and posttranslational processing, or nonprocessed cytosolic
      forms have elicited disparate levels of protection in the mouse model. We have
      now used the unique functional properties of this molecule to investigate the
      structural requirements needed to elicit a protective immune response. Genetic
      and physicochemical alterations to DbpA showed that the ability to bind to the
      ligand decorin is indicative of a potent immunogen but is not conclusive. By
      mutating the two carboxy-terminal nonconserved cysteines of DbpA from B.
      burgdorferi strain N40, we have determined that the stability afforded by the
      putative disulfide bond is essential for the generation of protective antibodies.
      This mutated protein was more sensitive to thermal denaturation and proteolysis,
      suggesting that it is in a less ordered state. Immunization with DbpA that was
      thermally denatured and functionally inactivated stimulated an immune response
      that was not protective and lacked bactericidal antibodies. Antibodies against
      conformationally altered forms of DbpA also failed to kill heterologous B.
      garinii and B. afzelii strains. Additionally, nonsecreted recombinant forms of
      DbpA(N40) were found to be inferior to secreted lipoprotein DbpA(N40) in terms of
      functional activity and antigenic potency. These data suggest that elicitation of
      a bactericidal and protective immune response to DbpA requires a properly folded
      conformation for the production of functional antibodies.

PMID- 11447154
TI  - Endogenous interleukin-12 is not required for resolution of Chlamydophila abortus
      (Chlamydia psittaci serotype 1) infection in mice.
AB  - A Th1 immune response involving gamma interferon (IFN-gamma) production is
      required to eliminate Chlamydophila abortus infections. In this study, the role
      of interleukin-12 (IL-12) in protecting against C. abortus infection was
      investigated using IL-12(-/-) and wild-type (WT) C57BL/6 mice to determine the
      role of this Th1-promoting cytokine. IL-12(-/-) mice were able to eliminate the
      C. abortus infection in a primary infection. However, there was a delay in the
      clearance of bacteria when IL-12(-/-) mice were infected with a sublethal dose of
      C. abortus, the delay being associated with a lower production of IFN-gamma. The
      low level of IFN-gamma was essential for survival of IL-12(-/-) infected mice.
      Both WT and IL-12(-/-) mice developed a Th1 immune response against C. abortus
      infection, since they both produced IFN-gamma and immunoglobulin G2a antibody
      isotype. In addition, when mice were given a secondary infectious challenge with
      C. abortus, a protective host response which resolved the secondary infection was
      developed by both WT and IL-12(-/-) mice. The lack of IL-12 resulted in few
      infiltrating CD4(+) T cells in the liver relative to the number in WT mice,
      although the number of CD8(+) T cells was slightly higher. The more intense Th1
      response presented by WT mice may have a pathogenic effect, as the animals showed
      higher morbidity after the infection. In conclusion, these results suggest that
      although IL-12 expedites the clearance of C. abortus infection, this cytokine is
      not essential for the establishment of a protective host response against the
      infection.

PMID- 11447155
TI  - Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination
      with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides
      as adjuvant.
AB  - The P39 and the bacterioferrin (BFR) antigens of Brucella melitensis 16M were
      previously identified as T dominant antigens able to induce both delayed-type
      hypersensivity in sensitized guinea pigs and in vitro gamma interferon (IFN
      gamma) production by peripheral blood mononuclear cells from infected cattle.
      Here, we analyzed the potential for these antigens to function as a subunitary
      vaccine against Brucella abortus infection in BALB/c mice, and we characterized
      the humoral and cellular immune responses induced. Mice were injected with each
      of the recombinant proteins alone or adjuvanted with either CpG
      oligodeoxynucleotides (CpG ODN) or non-CpG ODN. Mice immunized with the
      recombinant antigens with CpG ODN were the only group demonstrating both
      significant IFN-gamma production and T-cell proliferation in response to either
      Brucella extract or to the respective antigen. The same conclusion holds true for
      the antibody response, which was only demonstrated in mice immunized with
      recombinant antigens mixed with CpG ODN. The antibody titers (both immunoglobulin
      G1 [IgG1] and IgG2a) induced by P39 immunization were higher than the titers
      induced by BFR (only IgG2a). Using a B. abortus 544 challenge, the level of
      protection was analyzed and compared to the protection conferred by one
      immunization with the vaccine strain B19. Immunization with P39 and CpG ODN gave
      a level of protection comparable to the one conferred by B19 at 4 weeks
      postchallenge, and the mice were still significantly protected at 8 weeks
      postchallenge, although to a lesser extent than the B19-vaccinated group.
      Intriguingly, no protection was detected after BFR vaccination. All other groups
      did not demonstrate any protection.

PMID- 11447156
TI  - Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of
      tumor necrosis factor alpha production during infection of human macrophages.
AB  - Brucella spp. can establish themselves and cause disease in humans and animals.
      The mechanisms by which Brucella spp. evade the antibacterial defenses of their
      host, however, remain largely unknown. We have previously reported that live
      brucellae failed to induce tumor necrosis factor alpha (TNF-alpha) production
      upon human macrophage infection. This inhibition is associated with a
      nonidentified protein that is released into culture medium. Outer membrane
      proteins (OMPs) of gram-negative bacteria have been shown to modulate macrophage
      functions, including cytokine production. Thus, we have analyzed the effects of
      two major OMPs (Omp25 and Omp31) of Brucella suis 1330 (wild-type [WT] B. suis)
      on TNF-alpha production. For this purpose, omp25 and omp31 null mutants of B.
      suis (Deltaomp25 B. suis and Deltaomp31 B. suis, respectively) were constructed
      and analyzed for the ability to activate human macrophages to secrete TNF-alpha.
      We showed that, in contrast to WT B. suis or Deltaomp31 B. suis, Deltaomp25 B.
      suis induced TNF-alpha production when phagocytosed by human macrophages. The
      complementation of Deltaomp25 B. suis with WT omp25 (Deltaomp25-omp25 B. suis
      mutant) significantly reversed this effect: Deltaomp25-omp25 B. suis-infected
      macrophages secreted significantly less TNF-alpha than did macrophages infected
      with the Deltaomp25 B. suis mutant. Furthermore, pretreatment of WT B. suis with
      an anti-Omp25 monoclonal antibody directed against an epitope exposed at the
      surface of the bacteria resulted in substancial TNF-alpha production during
      macrophage infection. These observations demonstrated that Omp25 of B. suis is
      involved in the negative regulation of TNF-alpha production upon infection of
      human macrophages.

PMID- 11447157
TI  - Demonstration of the genetic stability and temporal expression of select members
      of the lyme disease spirochete OspF protein family during infection in mice.
AB  - Infection with Lyme disease spirochetes can be chronic. This suggests that the
      spirochetes are capable of immune evasion. In a previous study we demonstrated
      that the ospE gene family, which is one of three gene families whose members are
      flanked at their 5' end by the highly conserved upstream homology box (UHB)
      element, undergoes mutation and rearrangement during infection. This results in
      the generation of antigenically distinct variants that may contribute to immune
      evasion. In this study we have assessed the genetic stability of the UHB-flanked
      ospF gene family during infection in mice. Using postinfection clonal populations
      of Borrelia burgdorferi B31MI, PCR amplicons were generated for three members of
      the ospF gene family after a 3-month infection time frame. The amplicons were
      analyzed by single-nucleotide polymorphism pattern analysis and DNA sequencing.
      Members of the ospF gene family were found to be stable during infection, as no
      mutations or rearrangements were detected. An analysis of the humoral immune
      response to these proteins during infection revealed that the immune response to
      each is specific and that there is a delayed humoral immune response to some OspF
      protein family members. These analyses suggest that there is a temporal component
      to the expression of these genes during infection. In addition to a possible
      contribution to immune evasion, members of the OspF protein family may play
      specific roles at different stages of infection.

PMID- 11447158
TI  - Induction of cell-mediated immunity against Mycobacterium tuberculosis using DNA
      vaccines encoding cytotoxic and helper T-cell epitopes of the 38-kilodalton
      protein.
AB  - Cell-mediated immune responses are crucial in the protection against
      tuberculosis. In this study, we constructed DNA vaccines encoding cytotoxic T
      lymphocytes (CTL) and T helper cell (Th) epitopes of the 38-kDa lipoglycoprotein
      of Mycobacterium tuberculosis and analyzed and compared their immunogenicities
      with that of pXJ38, a DNA vaccine encoding the entire 38-kDa protein (X. Zhu, N.
      Venkataprasad, H. S. Thangaraj, M. Hill, M. Singh, J. Ivanyi, and H. M.
      Vordermeier, J. Immunol. 158:5921-5926, 1997). Plasmid DNAs encoding a CTL
      epitope, P3 (pP3), a Th epitope (vTh), or both the Th and the P3 epitopes (pThP3)
      were prepared and tested in C57BL6/J (H-2(b)) mice. Our results confirmed that
      DNA immunization with pXJ38 induces strong CD8(+) CTL and Th1 responses (high
      gamma interferon [IFN-gamma], low interleukin-4 [IL-4]). Coadministration of
      plasmid DNAs encoding a Th epitope with those encoding a CTL epitope (vTh+pP3)
      elicited both antigen-specific CD8(+) CTL and Th1 responses. High levels of IFN
      gamma were secreted by spleen cells from all plasmid DNA-vaccinated mice after in
      vitro stimulation with the recombinant 38-kDa protein. Small or undetectable
      amounts of IL-4 were observed, which indicates the induction of a Th1-like
      response. Multiple-epitope vaccination by vTh+pP3 or pThP3 resulted in a broader
      Th1 response to peptide or epitopes than the single-epitope plasmid DNAs. Antigen
      specific immunoglobulin G2a was only detected in sera from mice immunized with
      the plasmid pXJ38, and not in mice immunized with the epitope-based DNA vaccines.
      Thus, the absence of an antibody response after immunization with epitope plasmid
      DNAs and their ability to trigger only a specific cellular immune response may
      prove to be important advantages for a vaccine against tuberculosis.

PMID- 11447159
TI  - Immunoglobulin A-mediated protection against Bordetella pertussis infection.
AB  - Infection with Bordetella pertussis, the causative agent of pertussis (whooping
      cough) in humans, is followed by the production of antibodies of several
      isotypes, including immunoglobulin A (IgA). Little is known, however, about the
      role of IgA in immunity against pertussis. Therefore, we studied targeting of B.
      pertussis to the myeloid receptor for IgA, FcalphaRI (CD89), using either IgA
      purified from immune sera of pertussis patients or bispecific antibodies directed
      against B. pertussis and FcalphaRI (CD89 BsAb). Both IgA and CD89 BsAb
      facilitated FcalphaRI-mediated binding, phagocytosis, and bacterial killing by
      human polymorphonuclear leukocytes (PMNL) and PMNL originating from human
      FcalphaRI-transgenic mice. Importantly, FcalphaRI targeting resulted in enhanced
      bacterial clearance in lungs of transgenic mice. These data support the capacity
      of IgA to induce anti-B. pertussis effector functions via the myeloid IgA
      receptor, FcalphaRI. Increasing the amount of IgA antibodies induced by pertussis
      vaccines may result in higher vaccine efficacy.

PMID- 11447160
TI  - Identification and characterization of a novel secreted immunoglobulin binding
      protein from group A streptococcus.
AB  - Immunoglobulin binding proteins are one of several pathogenicity factors which
      have been associated with invasive disease caused by group A streptococci. The
      surface-bound M and M-like proteins of Streptococcus pyogenes are the most
      characterized of these immunoglobulin binding proteins, and in most cases they
      bind only a single antibody class. Here we report the identification of a novel
      non-M-type secreted protein, designated SibA (for secreted immunoglobulin binding
      protein from group A streptococcus), which binds all immunoglobulin G (IgG)
      subclasses, the Fc and Fab fragments, and also IgA and IgM. SibA has no
      significant sequence homology to any M-related proteins, is not found in the vir
      regulon, and contains none of the characteristic M-protein regions, such as the A
      or C repeats. Like M proteins, however, SibA does have relatively high levels of
      alanine, lysine, glutamic acid, leucine, and glycine. SibA and M proteins also
      share an alpha-helical N-terminal secondary structure which has been previously
      implicated in immunoglobulin binding in M proteins. Evidence presented here
      indicates that this is also the case for SibA. SibA also has regions of local
      similarity with other coiled-coil proteins such as Listeria monocytogenes P45
      autolysin, human myosin heavy chain, macrogolgin, and Schistoma mansoni
      paramyosin, some of which are of potential significance since cross-reactive
      antibodies between myosin proteins and M proteins have been implicated in the
      development of the autoimmune sequelae of streptococcal disease.

PMID- 11447161
TI  - Directional gene movement from human-pathogenic to commensal-like streptococci.
AB  - Group A streptococci (GAS) are highly pathogenic for humans, and their closest
      genetic relatives, group C and G streptococci (GCS and GGS, respectively), are
      generally regarded as commensals, although they can be found in association with
      human disease. As part of an effort to better understand the evolution of
      virulence, the phylogenetic relationships between GAS, GCS, and GGS were
      examined. The nucleotide sequence was determined for an internal portion of seven
      housekeeping (neutral) loci among >200 isolates of GAS and 34 isolates of GCS or
      GGS obtained from human subjects. Genotypic analysis failed to show support for
      the separation of GCS and GGS into two distinct populations. Unlike GAS, there
      was poor concordance between emm type and genetic relatedness among GCS and GGS.
      All housekeeping genes within GAS displayed relatively low levels of sequence
      diversity. In contrast, individual GCS and GGS strains had mosaic genomes,
      containing alleles at some loci that were similar or identical to GAS alleles,
      whereas the alleles at other loci were about 10 to 30% diverged. The data provide
      evidence for a history of recent interspecies transfer of neutral genes that
      exhibits a strong net directionality from GAS donors to GCS and GGS recipients. A
      model for the evolution of GAS and of GCS and GGS is described.

PMID- 11447162
TI  - Intranasal immunization with killed unencapsulated whole cells prevents
      colonization and invasive disease by capsulated pneumococci.
AB  - A whole-cell killed unencapsulated pneumococcal vaccine given by the intranasal
      route with cholera toxin as an adjuvant was tested in two animal models. This
      vaccination was highly effective in preventing nasopharyngeal colonization with
      an encapsulated serotype 6B strain in mice and also conferred protection against
      illness and death in rats inoculated intrathoracically with a highly encapsulated
      serotype 3 strain. When the serotype 3 challenge strain was incubated in the sera
      of immunized rats, it was no longer virulent in an infant-rat sepsis model,
      indicating that the intranasal immunization elicited protective systemic
      antibodies. These studies suggest that killed whole-cell unencapsulated
      pneumococci given intranasally with an adjuvant may provide multitypic protection
      against capsulated pneumococci.

PMID- 11447163
TI  - Characterization of a stress-induced alternate sigma factor, RpoS, of Coxiella
      burnetii and its expression during the development cycle.
AB  - Coxiella burnetii is an obligate intracellular bacterium that resides in an
      acidified phagolysosome and has a remarkable ability to persist in the
      extracellular environment. C. burnetii has evolved a developmental cycle that
      includes at least two morphologic forms, designated large cell variants (LCV) and
      small cell variants (SCV). Based on differential protein expression, distinct
      ultrastructures, and different metabolic activities, we speculated that LCV and
      SCV are similar to typical logarithmic- and stationary-phase growth stages. We
      hypothesized that the alternate sigma factor, RpoS, a global regulator of genes
      expressed under stationary-phase, starvation, and stress conditions in many
      bacteria, regulates differential expression in life cycle variants of C.
      burnetii. To test this hypothesis, we cloned and characterized the major sigma
      factor, encoded by an rpoD homologue, and the stress response sigma factor,
      encoded by an rpoS homologue. The rpoS gene was cloned by complementation of an
      Escherichia coli rpoS null mutant containing an RpoS-dependent lacZ fusion
      (osmY::lacZ). Expression of C. burnetii rpoS was regulated by growth phase in E.
      coli (induced upon entry into stationary phase). A glutathione S-transferase-RpoS
      fusion protein was used to develop polyclonal antiserum against C. burnetii RpoS.
      Western blot analysis detected abundant RpoS in LCV but not in SCV. These results
      suggest that LCV and SCV are not comparable to logarithmic and stationary phases
      of growth and may represent a novel adaptation for survival in both the
      phagolysosome and the extracellular environment.

PMID- 11447164
TI  - Immunogenicity of well-characterized synthetic Plasmodium falciparum multiple
      antigen peptide conjugates.
AB  - Given the emerging difficulties with malaria drug resistance and vector control,
      as well as the persistent lack of an effective vaccine, new malaria vaccine
      development strategies are needed. We used a novel methodology to synthesize and
      fully characterize multiple antigen peptide (MAP) conjugates containing
      protective epitopes from Plasmodium falciparum and evaluated their immunogenicity
      in four different strains of mice. A di-epitope MAP (T3-T1) containing two T-cell
      epitopes of liver stage antigen-1 (LSA-1), a di-epitope MAP containing T-cell
      epitopes from LSA-1 and from merozoite surface protein-1, and a tri-epitope MAP
      (T3-CS-T1) containing T3-T1 and a potent B-cell epitope from the circumsporozoite
      protein central repeat region were tested in this study. Mice of all four strains
      produced peptide-specific antibodies; however, the magnitude of the humoral
      response indicated strong genetic restriction between the different strains of
      mice. Anti-MAP antibodies recognized stage-specific proteins on the malaria
      parasites in an immunofluorescence assay. In addition, serum from hybrid BALB/cJ
      x A/J CAF1 mice that had been immunized with the tri-epitope MAP T3-CS-T1
      successfully inhibited the malaria sporozoite invasion of hepatoma cells in
      vitro. Spleen cells from immunized mice also showed a genetically restricted
      cellular immune response when stimulated with the immunogen in vitro. This study
      indicates that well-characterized MAPs combining solid-phase synthesis and
      conjugation chemistries are potent immunogens and that this approach can be
      utilized for the development of subunit vaccines.

PMID- 11447165
TI  - Nickel-responsive induction of urease expression in Helicobacter pylori is
      mediated at the transcriptional level.
AB  - The nickel-containing enzyme urease is an essential colonization factor of the
      gastric pathogen Helicobacter pylori, as it allows the bacterium to survive the
      acidic conditions in the gastric mucosa. Although urease can represents up to 10%
      of the total protein content of H. pylori, expression of urease genes is thought
      to be constitutive. Here it is demonstrated that H. pylori regulates the
      expression and activity of its urease enzyme as a function of the availability of
      the cofactor nickel. Supplementation of brucella growth medium with 1 or 100
      microM NiCl(2) resulted in up to 3.5-fold-increased expression of the urease
      subunit proteins UreA and UreB and up to 12-fold-increased urease enzyme
      activity. The induction was specific for nickel, since the addition of cadmium,
      cobalt, copper, iron, manganese, or zinc did not affect the expression of urease.
      Both Northern hybridization studies and a transcriptional ureA::lacZ fusion
      demonstrated that the observed nickel-responsive regulation of urease is mediated
      at the transcriptional level. Mutation of the HP1027 gene, encoding the ferric
      uptake regulator (Fur), did not affect the expression of urease in unsupplemented
      medium but reduced the nickel induction of urease expression to only twofold.
      This indicates that Fur is involved in the modulation of urease expression in
      response to nickel. These data demonstrate nickel-responsive regulation of H.
      pylori urease, a phenomenon likely to be of importance during the colonization
      and persistence of H. pylori in the gastric mucosa.

PMID- 11447166
TI  - Neutrophil depletion during Toxoplasma gondii infection leads to impaired
      immunity and lethal systemic pathology.
AB  - The immunomodulatory role of neutrophils during infection with Toxoplasma gondii
      was investigated. Monoclonal antibody-mediated depletion revealed that
      neutrophils are essential for survival during the first few days of infection.
      Moreover, neutrophil depletion was associated with a weaker type 1 immune
      response as measured by decreased levels of gamma interferon, interleukin-12 (IL
      12) and tumor necrosis factor alpha. IL-10 was also decreased in depleted
      animals. Additionally, splenic populations of CD4(+) T cells, CD8(+) T cells, and
      NK1.1(+) cells were decreased in depleted mice. Neutrophil-depleted mice
      exhibited lesions of greater severity in tissues examined and a greater parasite
      burden as determined by histopathology and reverse transcription-PCR. We conclude
      that neutrophils are critical near the time of infection because they influence
      the character of the immune response and control tachyzoite replication.

PMID- 11447167
TI  - Heterogeneity of wild Leishmania major isolates in experimental murine
      pathogenicity and specific immune response.
AB  - Virulence variability was investigated by analyzing the experimental
      pathogenicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve
      strains were isolated from Tunisian patients with zoonotic cutaneous
      leishmaniasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n =
      2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind
      footpad with 2 x 10(6) amastigotes of the various isolates, and lesion
      progression was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma
      interferon (IFN-gamma) production of lymph node mononuclear cells activated in
      vitro with parasite antigens were evaluated 5 weeks after infection. We show that
      disease progression induced by different L. major isolates was largely
      heterogeneous although reproducible results were obtained when using the same
      isolate. Interestingly, isolates from the Middle East induced a more severe
      disease than did the majority of Tunisian isolates. Strains with the highest
      virulence tend to generate more IL-4 and less IFN-gamma in vitro at week 5
      postinfection as well as higher levels of early IL-4 mRNA in the lymph node
      draining the inoculation site at 16 h postinfection. These results suggest that
      L. major isolates from the field may differ in virulence, which influences the
      course of the disease induced in mice and the type of immune response elicited by
      the infected host.

PMID- 11447168
TI  - Diversity in antistaphylococcal mechanisms among membrane-targeting antimicrobial
      peptides.
AB  - Many antimicrobial peptides permeabilize the bacterial cytoplasmic membrane.
      However, it is unclear how membrane permeabilization and antimicrobial activity
      are related for distinct peptides. This study investigated the relationship
      between Staphylococcus aureus membrane permeabilization and cell death due to the
      following antistaphylococcal peptides: thrombin-induced platelet microbicidal
      protein 1 (tPMP-1), gramicidin D, and protamine. Isogenic S. aureus strains
      ISP479C and ISP479R (tPMP-1 susceptible and resistant, respectively), were loaded
      with the fluorochrome calcein and exposed to a range of concentrations of each
      peptide. Flow cytometry was then used to monitor membrane permeabilization by
      quantifying the release of preloaded calcein. Killing was determined by
      quantitative culture at time points simultaneous to measurement of membrane
      permeabilization. Membrane permeabilization and killing caused by tPMP-1 occurred
      in a time- and concentration-dependent manner, reflecting the intrinsic tPMP-1
      susceptibilities of ISP479C and ISP479R. In comparison, gramicidin D killed both
      S. aureus strains to equivalent extents in a concentration-dependent manner
      between 0.5 to 50 microg/ml, but cell permeabilization only occurred at the
      higher peptide concentrations (25 and 50 microg/ml). Protamine permeabilized, but
      did not kill, either strain at concentrations up to 10 mg/ml. Regression analyses
      revealed different relationships between membrane permeabilization and
      staphylocidal activity for the distinct antimicrobial peptides. Taken together,
      these findings demonstrate that permeabilization, per se, does not invariably
      result in staphylococcal death due to distinct antimicrobial peptides. Thus,
      although each of these peptides interacts with the S. aureus cytoplasmic
      membrane, diversity exists in their mechanisms of action with respect to the
      relationship between membrane permeabilization and staphylocidal activity.

PMID- 11447169
TI  - Escherichia coli enterotoxin B subunit triggers apoptosis of CD8(+) T cells by
      activating transcription factor c-myc.
AB  - Heat-labile enterotoxin from enterotoxinogenic Escherichia coli is not only an
      important cause of diarrhea in humans and domestic animals but also possesses
      potent immunomodulatory properties. Recently, the nontoxic, receptor-binding B
      subunit of heat-labile enterotoxin (EtxB) was found to induce the selective death
      of CD8(+) T cells, suggesting that EtxB may trigger activation of proapoptotic
      signaling pathways. Here we show that EtxB treatment of CD8(+) T cells but not of
      CD4(+) T cells triggers the specific up-regulation of the transcription factor c
      myc, implicated in the control of cell proliferation, differentiation, and death.
      A concomitant elevation in Myc protein levels was also evident, with peak
      expression occurring 4 h posttreatment. Preincubation with c-myc antisense
      oligodeoxynucleotides demonstrated that Myc expression was necessary for EtxB
      mediated apoptosis. Myc activation was also associated with an increase of
      IkappaBalpha turnover, suggesting that elevated Myc expression may be dependent
      on NF-kappaB. When CD8(+) T cells were pretreated with inhibitors of IkappaBalpha
      turnover and NF-kappaB translocation, this resulted in a marked reduction in both
      EtxB-induced apoptosis and Myc expression. Further, a non-receptor-binding mutant
      of EtxB, EtxB(G33D), was shown to lack the capacity to activate Myc
      transcription. These findings provide further evidence that EtxB is a signaling
      molecule that triggers activation of transcription factors involved in cell
      survival.

PMID- 11447170
TI  - FlhA, a component of the flagellum assembly apparatus of Pseudomonas aeruginosa,
      plays a role in internalization by corneal epithelial cells.
AB  - Pseudomonas aeruginosa invades various epithelial cell types in vitro and in
      vivo. The P. aeruginosa genome possesses a gene (flhA) which encodes a protein
      that is believed to be part of the export apparatus for flagellum assembly and
      which is homologous to invA of Salmonella spp. Because invA is required for
      invasion of Salmonella spp., a role for flhA in P. aeruginosa invasion was
      explored using cultured rabbit corneal epithelial cells. An flhA mutant of P.
      aeruginosa strain PAO1 was constructed and was shown to be nonmotile.
      Complementation with flhA in trans restored motility. Corneal cells were infected
      for 3 h with the wild type (PAO1), the flhA mutant, the flhA mutant complemented
      with flhA in trans, an flhA mutant containing the plasmid vector control, or an
      fliC mutant (nonmotile mutant control). Invasion was quantified by amikacin
      exclusion assays. Both the flhA and the fliC mutants invaded at a lower level
      than the wild-type strain did, suggesting that both fliC and flhA played roles in
      invasion. However, loss of motility was not sufficient to explain the reduced
      invasion by flhA mutants, since centrifugation of bacteria onto cells did not
      restore invasion to wild-type levels. Unexpectedly, the flhA mutant adhered
      significantly better to corneal epithelial cells than wild-type bacteria or the
      fliC mutant did. The percentage of adherent bacteria that invaded was reduced by
      approximately 80% for the flhA mutant and approximately 50% for the fliC mutant,
      showing that only part of the role of flhA in invasion involves fliC. Invasion
      was restored by complementing the flhA mutant with flhA in trans but not by the
      plasmid vector control. Intracellular survival assays, in which intracellular
      bacteria were enumerated after continued incubation in the presence of
      antibiotics, showed that although flhA and fliC mutants had a reduced capacity
      for epithelial cell entry, they were not defective in their ability to survive
      within those cells after entry. These results suggest that the flagellum assembly
      type III secretion system plays a role in P. aeruginosa invasion of epithelial
      cells. Since the flhA mutants were not defective in their ability to adhere to
      corneal epithelial cells, to retain viability at the cell surface, or to survive
      inside epithelial cells after entry, the role of flhA in invasion of epithelial
      cells is likely to occur during the process of bacterial internalization.

PMID- 11447171
TI  - Stress-induced ClpP serine protease of Listeria monocytogenes is essential for
      induction of listeriolysin O-dependent protective immunity.
AB  - The stress-induced protease ClpP is required for virulence of the facultative
      intracellular pathogen Listeria monocytogenes. We previously found that in the
      absence of ClpP, the virulence of this pathogen was strongly reduced, mainly due
      to the decreased production of functional listeriolysin O (LLO), a major
      immunodominant virulence factor promoting intracellular growth. In this work, a
      clpP deletion mutant of L. monocytogenes was used to study the generation of anti
      Listeria protective immunity. We found that ClpP is required for the
      intracellular growth of L. monocytogenes in resident macrophages in vivo. Mice
      infected with doses as high as 10(6) clpP mutant bacteria were not protected
      against a lethal challenge of wild-type bacteria and did not develop any
      detectable LLO-specific cytolytic T cells or antibodies, suggesting that the
      amount of LLO produced in infected mice under these conditions was too low to
      induce a specific immune response. However, in contrast to the results obtained
      with a mutant with a disrupted hly gene, this lack of protection was overcome by
      inoculation of very high infecting doses of clpP mutant bacteria (5 x 10(8)),
      thus producing sufficient amounts of LLO to stimulate anti-Listeria immunity. The
      role of ClpP was confirmed by showing that anti-Listeria immunity was restored in
      mice infected with a clpP-complemented mutant. These results indicate that the
      stress-induced serine protease ClpP is a potential target for modulating the
      presentation of protective antigens such as LLO and thereby the immune response
      against L. monocytogenes.

PMID- 11447172
TI  - Porphyromonas gingivalis fimbriae inhibit caspase-3-mediated apoptosis of
      monocytic THP-1 cells under growth factor deprivation via extracellular signal
      regulated kinase-dependent expression of p21 Cip/WAF1.
AB  - Apoptotic regulation of monocytes/macrophages appears to be closely associated
      with chronic inflammatory reactions. Since it was demonstrated earlier that
      certain bacterial cell components are involved in apoptotic regulation of these
      cells, in the present study, we investigated whether the bacterial fimbria, an
      important cell structure involved in bacterial adherence to host cells, regulates
      apoptosis of human monocytic THP-1 cells induced under growth factor deprivation.
      To investigate this point, we used fimbriae of Porphyromonas gingivalis, a
      pathogen causing periodontal disease, which is a chronic inflammatory disease.
      The fimbriae inhibited apoptosis of the cells under growth factor deprivation.
      This inhibitory action of the fimbriae was completely neutralized by anti
      fimbrial antibody. The fimbriae stimulated activation of extracellular signal
      regulated kinase (ERK) and expression of cyclin-dependent kinase inhibitor p21
      Cip/WAF1 (p21) in the cells. The stimulatory effect of the fimbriae on the
      expression of the p21 protein was inhibited by treatment with PD98059, a specific
      inhibitor of ERK. The cell apoptosis was inhibited by treatment with Ac-DEVD-CHO,
      an inhibitor of caspase-3. The fimbriae inhibited the serum withdrawal-induced
      cleavage of the caspase-3 proform and poly(ADP-ribose) polymerase, one of the
      caspase-3 substrates. Furthermore, PD98059 and antisense p21 oligonucleotide
      blocked the fimbrial inhibition of apoptosis and caspase-3 activation of the
      cells induced by serum withdrawal. These results show that the bacterial fimbriae
      inhibited apoptosis of THP-1 cells induced under growth factor deprivation via
      ERK-dependent expression of p21. The present study suggests that bacterial
      fimbriae act as potent regulators of chronic inflammatory disease, e.g.,
      periodontal disease, through blocking apoptosis of monocytes/macrophages.

PMID- 11447173
TI  - Monocytic cell activation by Nonendotoxic glycoprotein from Prevotella intermedia
      ATCC 25611 is mediated by toll-like receptor 2.
AB  - Lipopolysaccharide (LPS) preparations from gram-negative black-pigmented bacteria
      such as Porphyromonas gingivalis and Prevotella intermedia activate cells from
      non-LPS-responsive C3H/HeJ mice, but it is still unclear whether this activity is
      due to the unique structure of LPS or to a minor component(s) responsible for the
      activity in the preparation. A nonendotoxic glycoprotein with bioactivity against
      cells from C3H/HeJ mice was purified from a hot phenol-water extract of P.
      intermedia ATCC 25611 and designated Prevotella glycoprotein (PGP). Treatment of
      human monocytic THP-1 cells with 22-oxyacalcitriol (OCT) induced maturation and
      marked expression of CD14 on the cells, but the cells constitutively expressed
      Toll-like receptor 2 (TLR2) and TLR4 on the cells irrespective of the treatment.
      PGP induced a high level of interleukin-8 production at doses of 100 ng/ml and
      higher in OCT-treated THP-1 cells compared with Salmonella LPS, and the
      production was significantly inhibited by anti-CD14 and anti-TLR2 but not anti
      TLR4 antibodies. Consistent with this, TLR2-deficient murine macrophages did not
      respond to PGP. It was also shown that PGP activity on the THP-1 cells was LPS
      binding protein dependent and was inhibited by a synthetic lipid A precursor
      IV(A). These results indicate that PGP activates monocytic cells in a CD14- and
      TLR2-dependent manner.

PMID- 11447174
TI  - Leptospiral proteins recognized during the humoral immune response to
      leptospirosis in humans.
AB  - Leptospirosis is an emerging zoonosis caused by pathogenic spirochetes belonging
      to the genus Leptospira. An understanding of leptospiral protein expression
      regulation is needed to develop new immunoprotective and serodiagnostic
      strategies. We used the humoral immune response during human leptospirosis as a
      reporter of protein antigens expressed during infection. Qualitative and
      quantitative immunoblot analysis was performed using sera from 105 patients from
      Brazil and Barbados. Sera from patients with other diseases and healthy
      individuals were evaluated as controls. Seven proteins, p76, p62, p48, p45, p41,
      p37, and p32, were identified as targets of the humoral response during natural
      infection. In both acute and convalescent phases of illness, antibodies to
      lipopolysaccharide were predominantly immunoglobulin M (IgM) while antibodies to
      proteins were exclusively IgG. Anti-p32 reactivity had the greatest sensitivity
      and specificity: positive reactions were observed in 37 and 84% of acute- and
      convalescent-phase sera, respectively, while only 5% of community control
      individuals demonstrated positive reactions. Six immunodominant antigens were
      expressed by all pathogenic leptospiral strains tested; only p37 was
      inconsistently expressed. Two-dimensional immunoblots identified four of the
      seven infection-associated antigens as being previously characterized proteins:
      LipL32 (the major outer membrane lipoprotein), LipL41 (a surface-exposed outer
      membrane lipoprotein), and heat shock proteins GroEL and DnaK. Fractionation
      studies demonstrated LipL32 and LipL41 reactivity in the outer membrane fraction
      and GroEL and DnaK in the cytoplasmic fraction, while p37 appeared to be a
      soluble periplasmic protein. Most of the other immunodominant proteins, including
      p48 and p45, were localized to the inner membrane. These findings indicate that
      leptospiral proteins recognized during natural infection are potentially useful
      for serodiagnosis and may serve as targets for vaccine design.

PMID- 11447175
TI  - Construction and characterization of genetically defined aro omp mutants of
      enterotoxigenic Escherichia coli and preliminary studies of safety and
      immunogenicity in humans.
AB  - Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea in
      travelers to countries where the disease is endemic and causes a major disease
      burden in the indigenous population, particularly children. We describe here the
      generation and preclinical characterization of candidate strains of ETEC which
      are intended to provide the basis of a live attenuated oral vaccine to prevent
      this disease. It has been shown previously that a spontaneously arising toxin
      negative variant ETEC strain, E1392/75-2A, could confer 75% protection against
      challenge when administered to volunteers. Unfortunately this strain induced mild
      diarrhea in 15% of recipients. To eliminate the unacceptable reactogenicity of
      strain E1392/75-2A, it was further attenuated by introducing three different
      combinations of defined deletion mutations into the chromosome. A mouse
      intranasal model of immunization was developed and used to show that all of the
      strains were immunogenic. Immune responses against colonization factor antigens
      (CFAs) were particularly strong when the bacterial inocula were grown on "CFA
      agar," which induces strong expression of these antigens. Two of the strains were
      selected for a phase I dose escalation safety study with healthy adult
      volunteers. Freshly grown organisms were harvested from CFA agar plates and
      administered to volunteers as a suspension containing from 5 x 10(7) to 5 x 10(9)
      CFU. The vaccine was well tolerated at all doses and induced significant immune
      responses in all recipients at the highest dose of either strain. The results
      provide the basis for further clinical evaluation of these vaccine candidates.

PMID- 11447176
TI  - Cu,Zn superoxide dismutase of Mycobacterium tuberculosis contributes to survival
      in activated macrophages that are generating an oxidative burst.
AB  - Macrophages produce reactive oxygen species and reactive nitrogen species that
      have potent antimicrobial activity. Resistance to killing by macrophages is
      critical to the virulence of Mycobacterium tuberculosis. M. tuberculosis has two
      genes encoding superoxide dismutase proteins, sodA and sodC. SodC is a Cu,Zn
      superoxide dismutase responsible for only a minor portion of the superoxide
      dismutase activity of M. tuberculosis. However, SodC has a lipoprotein binding
      motif, which suggests that it may be anchored in the membrane to protect M.
      tuberculosis from reactive oxygen intermediates at the bacterial surface. To
      examine the role of the Cu,Zn superoxide dismutase in protecting M. tuberculosis
      from the toxic effects of exogenously generated reactive oxygen species, we
      constructed a null mutation in the sodC gene. In this report, we show that the M.
      tuberculosis sodC mutant is readily killed by superoxide generated externally,
      while the isogenic parental M. tuberculosis is unaffected under these conditions.
      Furthermore, the sodC mutant has enhanced susceptibility to killing by gamma
      interferon (IFN-gamma)-activated murine peritoneal macrophages producing
      oxidative burst products but is unaffected by macrophages not activated by IFN
      gamma or by macrophages from respiratory burst-deficient mice. These observations
      establish that the Cu,Zn superoxide dismutase contributes to the resistance of M.
      tuberculosis against oxidative burst products generated by activated macrophages.

PMID- 11447177
TI  - Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group a
      streptococcal isolates in vivo.
AB  - The streptococcal pyrogenic exotoxins (Spes) play a central role in the
      pathogenesis of invasive group A streptococcal (GAS) infections. The majority of
      recent invasive GAS infections have been caused by an M1T1 strain that harbors
      the genes for several streptococcal superantigens, including speA, speB, speF,
      speG, and smeZ. However, considerable variation in the expression of Spe proteins
      among clonal M1 isolates has been found, and many of the speA-positive M1 strains
      do not produce detectable amounts of SpeA in vitro. This study was designed to
      test the hypothesis that speA gene expression can be induced in vivo. A mouse
      infection chamber model that allows sequential sampling of GAS isolates at
      various time points postinfection was developed and used to monitor the kinetics
      of Spe production in vivo. Micropore Teflon diffusion chambers were implanted
      subcutaneously in BALB/c mice, and after 3 weeks the pores became sealed with
      connective tissue and sterile fluid containing a white blood cell infiltrate
      accumulated inside the infection chambers. Representative clonal M1T1 isolates
      expressing no detectable SpeA were inoculated into the implanted chambers, and
      the expression of SpeA in the aspirated aliquots of the chamber fluid was
      analyzed on successive days postinfection. Expression of SpeA was detected in the
      chamber fluid as early as days 3 to 5 postinfection in most animals, with a
      significant increase in expression by day 7 in all infected mice. Isolates
      recovered from the chamber and grown in vitro continued to produce SpeA even
      after 21 passages in vitro, suggesting stable switch on of the speA gene. A
      temporal relation between the upregulation of SpeA expression and the
      downregulation of SpeB expression was observed in vivo. These data suggest that
      in vivo host and/or environmental signals induced speA gene expression and
      suppressed speB gene expression. This underscores the role of the host-pathogen
      interaction in regulating the expression of streptococcal virulence factors in
      vivo. The model described here should facilitate such studies.

PMID- 11447178
TI  - Immune response to chlamydial 60-kilodalton heat shock protein in tears from
      Nepali trachoma patients.
AB  - Although the host immune response to the 60-kDa chlamydial heat shock protein
      (hsp60) has been implicated in trachoma pathogenesis, no studies have examined
      mucosal immune responses to hsp60 in populations for which chlamydia is endemic.
      Tears and sera from Nepali villagers were reacted against hsp60 fusion proteins,
      whole hsp60, and the major outer membrane protein (MOMP). Tears from villagers
      without disease were anti-hsp60 immunoglobulin G (IgG) reactive in 6 (38%) of 16
      villagers compared with 36 (90%) of 40 with follicular trachoma (TF) (P < 0.001);
      47 (89%) of 53 with inflammatory trachoma (TI) (P < 0.001); and 31 (84%) of 37
      with conjunctival scarring (TS) (P = 0.002). By multivariate analysis, odds
      ratios for tear hsp60 IgG immunoreactivity in villagers with TF, TI, and TS were
      49.2 (confidence interval [CI], 2.7 to 898), 22.6 (CI, 3 to 170), and 13.6 (CI,
      1.4 to 133), respectively. There were no significant differences for tear IgA or
      secretory IgA (sIgA) reactivity to hsp60 or for tear sIgA and IgG reactivity to
      MOMP. Serum anti-hsp60 IgG immunoreactivity was associated with TI only. These
      data suggest that anti-hsp60 IgG immunoreactivity represents largely locally
      derived antibodies, which may promote disease pathology. In contrast, nonspecific
      high rates of anti-hsp60 sIgA antibodies suggest chronic or repeat stimulation
      from an endemic source of organisms.

PMID- 11447179
TI  - Epithelial intestinal cell apoptosis induced by Helicobacter pylori depends on
      expression of the cag pathogenicity island phenotype.
AB  - Helicobacter pylori has been shown to induce chronic active gastritis and peptic
      ulcer and may contribute to the development of duodenal ulcer. Previous studies
      have shown that H. pylori mediates apoptosis of gastric epithelial cells via a
      Fas-dependent pathway. However, evidence for the induction of such a mechanism in
      intestinal epithelial cells (IEC) by H. pylori infection has not been
      demonstrated yet. This study was performed (i) to ascertain that H. pylori can
      induce IEC apoptosis; (ii) to delineate the role of the cag pathogenicity island
      (PAI), cagE, and vacA gene products in this process; and (iii) to verify whether
      the Fas-dependent pathway is involved in this phenomenon. When T84 cells were
      exposed to VacA(+)/cag PAI(+) H. pylori strains (CCUG 17874 and 60190), they
      exhibited apoptosis hallmarks as assessed by morphological studies, as well as
      annexin V and 3,3'-dihexyloxacarbocyanine iodide staining. In contrast, few or no
      apoptotic features could be detected after incubation with an isogenic mutant of
      strain 60190 in which the cagE gene was disrupted (60190:C(-) strain) or with a
      VacA(-)/cag PAI(-) H. pylori strain (G21). In addition, activation of caspase-3
      during infection with VacA(+)/cag PAI(+) H. pylori strains was inhibited by
      pretreatment of IEC with an antagonistic anti-Fas antibody (ZB4). Taken together,
      these findings indicate that H. pylori triggers apoptosis in IEC via a Fas
      dependent pathway following a process that depends on the expression of the cag
      PAI.

PMID- 11447180
TI  - Meningococcal outer membrane vesicle vaccine given intranasally can induce
      immunological memory and booster responses without evidence of tolerance.
AB  - We have studied the ability of outer membrane vesicle (OMV) vaccines from
      Neisseria meningitidis serogroup B to induce vaccine-specific antibody and spleen
      cell proliferative responses in mice after being administered intranasally (i.n.)
      and/or subcutaneously (s.c.). A series of four weekly i.n. doses (25 microg)
      without adjuvant or a single s.c. dose (2.5 microg) with aluminum hydroxide was
      followed 2 months later by secondary i.n. or s.c. immunizations. After i.n.
      priming, both immunoglobulin G (IgG) antibody responses in serum, measured by
      enzyme-linked immunosorbent assay, and IgA antibodies in saliva and extracts of
      feces were significantly boosted by later i.n. immunizations. The IgG antibody
      responses in serum were also significantly augmented by secondary s.c.
      immunization after i.n. as well as s.c. priming. Sera from mice immunized i.n.
      reached the same level of bactericidal activity as after s.c. immunizations. The
      s.c. immunizations alone, however, had no effect on mucosal IgA antibody
      responses, but could prime for booster antibody responses in secretions to later
      i.n. immunizations. The i.n. immunizations also led to marked OMV-specific spleen
      cell proliferation in vitro. Both serum antibody responses and spleen cell
      proliferation were higher after i.n. priming and later s.c. immunizations than
      after s.c. immunizations alone. There was thus no evidence that i.n. priming had
      induced immunological tolerance within the B- or T-cell system. Our results
      indicate that a nonproliferating meningococcal OMV vaccine given i.n. can induce
      immunological memory and that it may be favorably combined with similar vaccines
      for injections.

PMID- 11447181
TI  - Identification of Listeria monocytogenes in vivo-induced genes by fluorescence
      activated cell sorting.
AB  - Listeria monocytogenes is a gram-positive, intracellular, food-borne pathogen
      capable of causing severe infections in immunocompromised or pregnant
      individuals, as well as numerous animal species. Genetic analysis of Listeria
      pathogenesis has identified several genes which are crucial for virulence. The
      transcription of most of these genes has been shown to be induced upon entry of
      Listeria into the host cell. To identify additional genes that are induced in
      vivo and may be required for L. monocytogenes pathogenesis, a fluorescence
      activated cell-sorting technique was initiated. Random fragments of the L.
      monocytogenes chromosome were cloned into a plasmid carrying a promoterless green
      fluorescent protein (GFP) gene, and the plasmids were transformed into the L.
      monocytogenes actA mutant DP-L1942. Fluorescence-activated cell sorting (FACS)
      was used to isolate L. monocytogenes clones that exhibited increased GFP
      expression within macrophage-like J774 cells but had relatively low levels of GFP
      expression when the bacteria were extracellular. Using this strategy, several
      genes were identified, including actA, that exhibited such an expression profile.
      In-frame deletions of two of these genes, one encoding the putative L.
      monocytogenes uracil DNA glycosylase (ung) and one encoding a protein with
      homology to the Bacillus subtilis YhdP hemolysin-like protein, were constructed
      and introduced into the chromosome of wild-type L. monocytogenes 10403s. The L.
      monocytogenes 10403s ung deletion mutant was not attenuated for virulence in
      mice, while the yhdP mutant exhibited a three- to sevenfold reduction in
      virulence.

PMID- 11447182
TI  - Differential roles of interleukin-18 (IL-18) and IL12 for induction of gamma
      interferon by staphylococcal cell wall components and superantigens.
AB  - The roles of endogenous cytokines induced by either intact staphylococcal
      microorganisms or staphylococcal exotoxins were examined using human whole-blood
      cultures. To accomplish this, interleukin-18 binding protein (IL-18BP) and tumor
      necrosis factor binding protein (TNFbp) were used to neutralize IL-18 and TNF,
      respectively, whereas an anti-IL-12 monoclonal antibody was used to neutralize IL
      12 and the IL-1 receptor antagonist (IL-1Ra) was used to block IL-1 receptors.
      Heat-killed Staphylococcus epidermidis and Staphylococcus aureus, as well as the
      staphylococcal superantigens toxic shock syndrome toxin-1 (TSST-1) and
      staphylococcus enterotoxin B (SEB) induced gamma interferon (IFN-gamma)
      production. Staphylococcus spp.-induced production of IFN-gamma required the
      presence of endogenous IL-18, IL-12, and TNF. In contrast, TSST-1-induced IFN
      gamma was not significantly reduced in the presence of IL-18BP, anti-IL-12
      antibodies, IL-1Ra, or anti-TNFbp. SEB-induced IFN-gamma was significantly
      inhibited only by anti-IL-12 antibodies, indicating that endogenous IL-18, IL-1,
      and TNF are not required for SEB-induced IFN-gamma. In conclusion, the mechanisms
      of IFN-gamma stimulation by intact staphylococcal microorganisms and by exotoxins
      differ, and this is likely due to the different receptors which are triggered on
      the cell membranes. In contrast to its role in the interactions between
      staphylococci and host cells, IL-18 does not appear to play a major role in
      superantigen-induced IFN-gamma.

PMID- 11447183
TI  - Neisseria meningitidis lipopolysaccharide modulates the specific humoral immune
      response to neisserial porins but has no effect on porin-induced upregulation of
      costimulatory ligand B7-2.
AB  - The role of lipopolysaccharide (LPS) in the specific humoral response to
      meningococcal porins was investigated by measuring anti-PorA or -PorB antibody
      levels in mice immunized with wild-type meningococcal strain H44/76 or with its
      recently described LPS-negative mutant. Two murine strains were used for these
      immunizations: C3H/HeJ, which is LPS hyporesponsive, or C3H/HeOuJ, which is LPS
      responsive. A high level of anti-PorB immunoglobulin G (IgG) response was induced
      in both strains of mice immunized with either organism. The response induced by
      the wild-type strain was greater in C3H/HeOuJ mice than in C3H/HeJ mice, while
      the response induced by the LPS-negative mutant was similar in the two murine
      strains. Additionally, the anti-PorB response was similar in C3H/HeJ mice
      immunized with either bacterial strain. In general, the anti-PorA IgG response
      was lower than the anti-PorB response. These findings indicate that the presence
      of LPS is not essential for the induction of an antineisserial porin humoral
      response but can augment such a response. To determine whether LPS has any effect
      on the B-cell-stimulatory effect of neisserial porins (essential for the adjuvant
      activity of neisserial porins), B cells from both murine strains were incubated
      with outer membrane complexes (OMCs) prepared from strain H44/76 and its LPS
      negative mutant. OMCs from either meningococcal strain were able to increase the
      surface expression of the costimulatory ligand B7-2 on B cells from either murine
      strain. Consistent with previously reported findings, LPS does not significantly
      affect the ability of neisserial porins to induce the costimulatory ligand B7-2.

PMID- 11447184
TI  - Tandem repeat deletion in the alpha C protein of group B streptococcus is recA
      independent.
AB  - Group B streptococci (GBS) contain a family of protective surface proteins
      characterized by variable numbers of repeating units within the proteins. The
      prototype alpha C protein of GBS from the type Ia/C strain A909 contains a series
      of nine identical 246-bp tandem repeat units. We have previously shown that
      deletions in the tandem repeat region of the alpha C protein affect both the
      immunogenicity and protective efficacy of the protein in animal models, and these
      deletions may serve as a virulence mechanism in GBS. The molecular mechanism of
      tandem repeat deletion is unknown. To determine whether RecA-mediated homologous
      recombination is involved in this process, we identified, cloned, and sequenced
      the recA gene homologue from GBS. A strain of GBS with recA deleted,
      A909DeltarecA, was constructed by insertional inactivation in the recA locus.
      A909DeltarecA demonstrated significant sensitivity to UV light, and the 50%
      lethal dose of the mutant strain in a mouse intraperitoneal model of sepsis was
      20-fold higher than that of the parent strain. The spontaneous rate of tandem
      repeat deletion in the alpha C protein in vitro, as well as in our mouse model of
      immune infection, was studied using A909DeltarecA. We report that tandem repeat
      deletion in the alpha C protein does occur in the absence of a functional recA
      gene both in vitro and in vivo, indicating that tandem repeat deletion in GBS
      occurs by a recA-independent recombinatorial pathway.

PMID- 11447185
TI  - Comparison of pathogenesis and host immune responses to Candida glabrata and
      Candida albicans in systemically infected immunocompetent mice.
AB  - Cytokine-mediated host defense against Candida glabrata infection was compared to
      that against C. albicans, using immunocompetent murine models of systemic
      candidiasis. The pathogenesis of infection was evaluated morphologically and by
      culture of target organs, while the kinetics of induction of cytokine mRNAs and
      corresponding proteins were determined in kidneys by real-time reverse
      transcription-PCR and cytokine-specific murine enzyme-linked immunosorbent
      assays, respectively. Systemic infection with C. glabrata resulted in a chronic,
      nonfatal infection with recovery of organisms from kidneys, while intravenous
      inoculation with C. albicans resulted in rapid mortality with logarithmic growth
      of organisms in kidneys and recovery of C. albicans from the spleen, liver, and
      lungs. Survival of C. glabrata-infected mice was associated with rapid induction
      of mRNAs and corresponding immunoreactive proteins for the proinflammatory
      cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-12 (IL-12), and
      gamma interferon (IFN-gamma) and the lack of induction of protein for the anti
      inflammatory cytokine IL-10. In contrast, mortality in C. albicans-infected mice
      was associated with induction of mRNA and corresponding protein for IL-10 but
      delayed (i.e., TNF-alpha) or absent (i.e., IL-12 and IFN-gamma) induction of
      immunoreactive proinflammatory cytokines. Mice were subsequently treated with
      cytokine-specific neutralizing monoclonal antibodies (MAbs) to TNF-alpha, IL-12,
      or IFN-gamma, and the effect on growth of C. glabrata in kidneys was assessed.
      Neutralization of endogenous TNF-alpha resulted in a significant increase in C.
      glabrata organisms compared to similarly infected mice administered an isotype
      matched control MAb, while neutralization of endogenous IL-12 or IFN-gamma had no
      significant effect on C. glabrata replication. These results demonstrate that in
      response to intravenous inoculation of C. glabrata, immunocompetent mice develop
      chronic nonfatal renal infections which are associated with rapid induction of
      the proinflammatory cytokines TNF-alpha, IL-12, and IFN-gamma. Furthermore, TNF
      alpha plays a key role in host defense against systemic candidiasis caused by
      either C. glabrata or C. albicans, as the absence of endogenous TNF-alpha
      activity was associated with enhanced tissue burden in both infection models.

PMID- 11447186
TI  - Effects of nonsteroidal anti-inflammatory drugs on Helicobacter pylori-infected
      gastric mucosae of mice: apoptosis, cell proliferation, and inflammatory
      activity.
AB  - Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are two
      well-known important causative factors of gastric damage. While H. pylori
      increases apoptosis and the proliferation of gastric epithelial cells and is an
      important factor in peptic ulcer and gastric cancer, NSAIDs induce cell apoptosis
      and have antineoplastic effects. We investigated the effects of NSAIDs (a
      nonselective cyclooxygenase [COX] inhibitor [indomethacin] and a selective COX-2
      inhibitor [NS-398]) on the apoptosis and proliferation of gastric epithelial
      cells and gastric inflammation in H. pylori-infected mice. C57BL/6 mice were
      sacrificed 8 weeks after H. pylori SS1 inoculation. Indomethacin (2 mg/kg) or NS
      398 (10 mg/kg) was administered subcutaneously once daily for 10 days before
      sacrifice. The following were assessed: gastric inflammatory activity, gastric
      COX protein expression by Western blotting; gastric prostaglandin E(2) levels by
      enzyme immunoassay, apoptosis by terminal deoxynucleotidyltransferase-mediated
      dUTP nick end labeling, and cell proliferation by Ki67 immunostaining. Compared
      to the controls, H. pylori infection and/or NSAID treatment increased COX-1 and
      COX-2 protein expression. Gastric prostaglandin E(2) levels, apoptotic index,
      cell proliferation index, neutrophil activity, and the degree of chronic
      inflammation were all increased by H. pylori infection, and these effects were
      significantly decreased by indomethacin treatment. However, NS-398 treatment
      after H. pylori infection did not induce a significant reduction, although it did
      result in a tendency to decrease. These results show that NSAIDs can reverse the
      increased apoptosis and proliferation of epithelial cells and inflammatory
      activity in the stomachs of H. pylori-infected mice and that, like COX-2
      activation, COX-1 induction contributes to the change of gastric mucosal cell
      turnover and inflammation induced by H. pylori infection.

PMID- 11447187
TI  - Interaction between host complement and mosquito-midgut-stage Plasmodium berghei.
AB  - After ingestion by mosquitoes, gametocytes of malaria parasites become activated
      and form extracellular gametes that are no longer protected by the red blood cell
      membrane against immune effectors of host blood. We have studied the action of
      complement on Plasmodium developmental stages in the mosquito blood meal using
      the rodent malaria parasite Plasmodium berghei and rat complement as a model. We
      have shown that in the mosquito midgut, rat complement components necessary to
      initiate the alternative pathway (factor B, factor D, and C3) as well as C5 are
      present for several hours following ingestion of P. berghei-infected rat blood.
      In culture, 30 to 50% of mosquito midgut stages of P. berghei survived complement
      exposure during the first 3 h of development. Subsequently, parasites became
      increasingly sensitive to complement lysis. To investigate the mechanisms
      involved in their protection, we tested for C3 deposition on parasite surfaces
      and whether host CD59 (a potent inhibitor of the complement membrane attack
      complex present on red blood cells) was taken up by gametes while emerging from
      the host cell. Between 0.5 and 22 h, 90% of Pbs21-positive parasites were
      positive for C3. While rat red and white blood cells stained positive for CD59,
      Pbs21-positive parasites were negative for CD59. In addition, exposure of
      parasites to rat complement in the presence of anti-rat CD59 antibodies did not
      increase lysis. These data suggest that parasite or host molecules other than
      CD59 are responsible for the protection of malaria parasites against complement
      mediated lysis. Ongoing research aims to identify these molecules.

PMID- 11447188
TI  - Cell adhesion molecule and lymphocyte activation marker expression during
      experimental vaginal candidiasis.
AB  - Cell-mediated immunity by Th1-type CD4(+) T cells is the predominant host defense
      mechanism against mucosal candidiasis. However, studies using an estrogen
      dependent murine model of vaginal candidiasis have demonstrated little to no
      change in resident vaginal T cells during infection and no systemic T-cell
      infiltration despite the presence of Candida-specific systemic Th1-type responses
      in infected mice. The present study was designed to further investigate these
      observations by characterizing T-cell activation and cell adhesion molecule
      expression during primary and secondary C. albicans vaginal infections. While
      flow cytometry analysis of activation markers showed some evidence for activation
      of CD3(+) draining lymph node and/or vaginal lymphocytes during both primary and
      secondary vaginal Candida infection, CD3(+) cells expressing the homing receptors
      and integrins alpha(4)beta(7), alpha(M290)beta(7), and alpha(4)beta(1) in
      draining lymph nodes of mice with primary and secondary infections were reduced
      compared to results for uninfected mice. At the local level, few vaginal
      lymphocytes expressed integrins, with only minor changes observed during both
      primary and secondary infections. On the other hand, immunohistochemical analysis
      of vaginal cell adhesion molecule expression showed increases in mucosal
      addressin cell adhesion molecule 1 and vascular cell adhesion molecule 1
      expression during both primary and secondary infections. Altogether, these data
      suggest that although the vaginal tissue is permissive to cellular infiltration
      during a vaginal Candida infection, the reduced numbers of systemic cells
      expressing the reciprocal cellular adhesion molecules may preempt cellular
      infiltration, thereby limiting Candida-specific T-cell responses against
      infection.

PMID- 11447189
TI  - Vacuolating cytotoxin of Helicobacter pylori induces apoptosis in the human
      gastric epithelial cell line AGS.
AB  - Helicobacter pylori induces cell death by apoptosis. However, the apoptosis
      inducing factor is still unknown. The virulence factor vacuolating cytotoxin A
      (VacA) is a potential candidate, and thus its role in apoptosis induction was
      investigated in the human gastric epithelial cell line AGS. The supernatant from
      the vacA wild-type strain P12 was able to induce apoptotic cell death, whereas
      the supernatant from its isogenic mutant strain P14 could not. That VacA was
      indeed the apoptosis-inducing factor was demonstrated further by substantial
      reduction of apoptosis upon treatment of AGS cells with a supernatant
      specifically depleted of native VacA. Furthermore, a recombinant VacA produced in
      Escherichia coli was also able to induce apoptosis in AGS cells but failed to
      induce cellular vacuolation. These findings demonstrate that the vacuolating
      cytototoxin of H. pylori is a bacterial factor capable of inducing apoptosis in
      gastric epithelial cells.

PMID- 11447190
TI  - Bartonella henselae induces NF-kappaB-dependent upregulation of adhesion
      molecules in cultured human endothelial cells: possible role of outer membrane
      proteins as pathogenic factors.
AB  - The endothelium is a specific target for Bartonella henselae, and endothelial
      cell infection represents an important step in the pathogenesis of cat scratch
      disease and bacillary angiomatosis. Mechanisms of Bartonella-endothelial cell
      interaction as well as signaling pathways involved in target cell activation were
      analyzed. B. henselae strain Berlin-1, isolated from bacillary angiomatosis
      lesions of a human immunodeficiency virus-infected patient, potently stimulated
      human umbilical cord vein endothelial cells (HUVEC), as determined by NF-kappaB
      activation and enhanced adhesion molecule expression. These effects were
      accompanied by increased PMN rolling on and adhesion to infected endothelial cell
      monolayers, as measured in a parallel-plate flow chamber assay. Monoclonal
      antibodies against E-selectin significantly reduced PMN rolling and adhesion. In
      our hands, B. henselae Berlin-1 was substantially more active than the typing
      strain B. henselae ATCC 49882. E-selectin and ICAM-1 upregulation occurred for up
      to 9 days, as verified by Northern blotting and cell surface enzyme-linked
      immunosorbent assay. Induction of adhesion molecules was mediated via NF-kappaB
      activation and could be blocked by a specific NF-kappaB inhibitor. Additional
      studies indicated that B. henselae-induced effects did not require living
      bacteria or Bartonella lipopolysaccharides. Exposure of HUVEC to purified B.
      henselae outer membrane proteins (OMPs), however, reproduced all aspects of
      endothelial cell activation. In conclusion, B. henselae, the causative agent of
      cat scratch disease and bacillary angiomatosis, infects and activates endothelial
      cells. B. henselae OMPs are sufficient to induce NF-kappaB activation and
      adhesion molecule expression followed by enhanced rolling and adhesion of
      leukocytes. These observations identify important new properties of B. henselae,
      demonstrating its capacity to initiate a cascade of events culminating in a
      proinflammatory phenotype of infected endothelial cells.

PMID- 11447191
TI  - Contribution of Mn-cofactored superoxide dismutase (SodA) to the virulence of
      Streptococcus agalactiae.
AB  - Superoxide dismutases convert superoxide anions to molecular oxygen and hydrogen
      peroxide, which, in turn, is metabolized by catalases and/or peroxidases. These
      enzymes constitute one of the major defense mechanisms of cells against oxidative
      stress and hence play a role in the pathogenesis of certain bacteria. We
      previously demonstrated that group B streptococci (GBS) possess a single Mn
      cofactored superoxide dismutase (SodA). To analyze the role of this enzyme in the
      pathogenicity of GBS, we constructed a sodA-disrupted mutant of Streptococcus
      agalactiae NEM316 by allelic exchange. This mutant was subsequently cis
      complemented by integration into the chromosome of pAT113/Sp harboring the wild
      type sodA gene. The SOD specific activity detected by gel analysis in cell
      extracts confirmed that active SODs were present in the parental and complemented
      strains but absent in the sodA mutant. The growth rates of these strains in
      standing cultures were comparable, but the sodA mutant was extremely susceptible
      to the oxidative stress generated by addition of paraquat or hydrogen peroxide to
      the culture medium and exhibited a higher mutation frequency in the presence of
      rifampin. In mouse bone marrow-derived macrophages, the sodA mutant showed an
      increased susceptibility to bacterial killing by macrophages. In a mouse
      infection model, after intravenous injection the survival of the sodA mutant in
      the blood and the brain was markedly reduced in comparison to that of the
      parental and complemented strains whereas only minor effects on survival in the
      liver and the spleen were observed. These results suggest that SodA plays a role
      in GBS pathogenesis.

PMID- 11447192
TI  - Differences in levels of secreted locus of enterocyte effacement proteins between
      human disease-associated and bovine Escherichia coli O157.
AB  - Ongoing extensive epidemiological studies of verotoxin-carrying Escherichia coli
      O157 (stx(+) eae(+)) have shown this bacterial pathogen to be common in cattle
      herds in the United States and the United Kingdom. However, the incidence of
      disease in humans due to this pathogen is still very low. This study set out to
      investigate if there is a difference between strains isolated from human disease
      cases and those isolated from asymptomatic cattle which would account for the low
      disease incidence of such a ubiquitous organism. The work presented here has
      compared human disease strains from both sporadic and outbreak cases with a cross
      section, as defined by pulsed-field gel electrophoresis, of E. coli O157 strains
      from cattle. Human (n = 22) and bovine (n = 31) strains were genotyped for
      carriage of the genes for Shiga-like toxin types 1, 2, and 2c; E. coli secreted
      protein genes espA, espB, and espP; the enterohemolysin gene; eae (intimin); ast
      (enteroaggregative E. coli stable toxin [EAST]); and genes for common E. coli
      adhesins. Strains were also phenotyped for hemolysin, EspP, Tir, and EspD
      expression as well as production of actin and cytoskeletal rearrangement
      associated with attaching and effacing (A/E) lesions on HeLa cells. The
      genotyping confirmed that there was little difference between the two groups,
      including carriage of stx(2) and stx(2c), which was similar in both sets. ast
      alleles were confirmed to all contain mutations that would prevent EAST
      expression. espP mutations were found only in cattle strains (5 of 30). Clear
      differences were observed in the expression of locus of enterocyte effacement
      (LEE)-encoded factors between strains and in different media. EspD, as an
      indicator of LEE4 (espA, -B, and -D) expression, and Tir levels in supernatants
      were measured. Virtually all strains from both sources could produce EspD in
      Luria-Bertani broth, although at very different levels. Standard trichloroacetic
      acid precipitation of secreted proteins from tissue culture medium produced
      detectable levels of EspD from the majority of strains of human origin (15 of 20)
      compared with only a few (4 of 20) bovine strains (P < 0.001), which is
      indicative of much higher levels of protein secretion from the human strains.
      Addition of bovine serum albumin carrier protein before precipitation and
      enhanced detection techniques confirmed that EspD could be detected after growth
      in tissue culture medium for all strains, but levels from strains of human origin
      were on average 90-fold higher than those from strains of bovine origin. In
      general, levels of secretion also correlated with ability to form A/E lesions on
      HeLa cells, with only the high-level protein secretors in tissue culture medium
      exhibiting a localized adherence phenotype. This research shows significant
      differences between human- and bovine-derived E. coli O157 (stx(+) eae(+))
      strains and their production of certain LEE-encoded virulence factors. These data
      support the recent finding of Kim et al. (J. Kim, J. Nietfeldt, and A. K. Benson,
      Proc. Natl. Acad. Sci. USA 96:13288-13293, 1999) proposing different E. coli O157
      lineages in cattle and humans and extend the differential to the regulation of
      virulence factors. Potentially only a subset of E. coli O157 isolates (stx(+)
      eae(+)) in cattle may be capable of causing severe disease in humans.

PMID- 11447193
TI  - Invasive candidiasis stimulates hepatocyte and monocyte production of active
      transforming growth factor beta.
AB  - Candida albicans is an opportunistic fungal pathogen and a major cause of
      morbidity and mortality in patients with compromised immune function. The
      cytokine response to tissue invasion by C. albicans can influence the
      differentiation and function of lymphocytes and other mononuclear cells that are
      critical components of the host response. While the production of transforming
      growth factor beta (TGF-beta) has been documented in mice infected with C.
      albicans and is known to suppress phagocyte function, the cellular source and
      role of this cytokine in the pathogenesis of systemic candidiasis are not well
      understood. We have investigated the source of production of TGF-beta by
      immunohistochemical studies in tissue samples from patients with an uncommon
      complication of lymphoreticular malignancy, chronic disseminated candidiasis
      (CDC), and from a neutropenic-rabbit model of CDC. Liver biopsy specimens from
      patients with documented CDC demonstrated intense staining for extracellular
      matrix-associated TGF-beta1 within inflammatory granulomas, as well as staining
      for TGF-beta1 and TGF-beta3 within adjacent hepatocytes. These results correlate
      with the immunolocalization of TGF-beta observed in livers of infected
      neutropenic rabbits, using a neutralizing antibody that recognizes the mature TGF
      beta protein. Human peripheral blood monocytes incubated with C. albicans in
      vitro release large amounts of biologically active TGF-beta1. The data
      demonstrate that local production of active TGF-betas by hepatocytes and by
      infected mononuclear cells is a component of the response to C. albicans
      infection that most probably contributes to disease progression in the
      immunocompromised host.

PMID- 11447194
TI  - Arginine-specific protease from Porphyromonas gingivalis activates protease
      activated receptors on human oral epithelial cells and induces interleukin-6
      secretion.
AB  - Periodontitis is a chronic inflammatory disease affecting oral tissues. Oral
      epithelial cells represent the primary barrier against bacteria causing the
      disease. We examined the responses of such cells to an arginine-specific cysteine
      proteinase (RgpB) produced by a causative agent of periodontal disease,
      Porphyromonas gingivalis. This protease caused an intracellular calcium transient
      in an oral epithelial cell line (KB), which was dependent on its enzymatic
      activity. Since protease-activated receptors (PARs) might mediate such signaling,
      reverse transcription-PCR was used to characterize the range of these receptors
      expressed in the KB cells. The cells were found to express PAR-1, PAR-2, and PAR
      3, but not PAR-4. In immunohistochemical studies, human gingival epithelial cells
      were found to express PAR-1, PAR-2, and PAR-3 on their surface, but not PAR-4,
      indicating that the cell line was an effective model for the in vivo situation.
      PAR-1 and PAR-2 expression was confirmed in intracellular calcium mobilization
      assays by treatment of the cells with the relevant receptor agonist peptides.
      Desensitization experiments strongly indicated that signaling of the effects of
      RgpB was occurring through PAR-1 and PAR-2. Studies with cells individually
      transfected with each of these two receptors confirmed that they were both
      activated by RgpB. Finally, it was shown that, in the oral epithelial cell line,
      PAR activation by the bacterial protease-stimulated secretion of interleukin-6.
      This induction of a powerful proinflammatory cytokine suggests a mechanism
      whereby cysteine proteases from P. gingivalis might mediate inflammatory events
      associated with periodontal disease on first contact with a primary barrier of
      cells.

PMID- 11447195
TI  - Chlamydia trachomatis persistence in the female mouse genital tract: inducible
      nitric oxide synthase and infection outcome.
AB  - It was previously reported that female mice resolve a primary Chlamydia
      trachomatis urogenital infection independent of inducible nitric oxide synthase
      (iNOS). We now report that although iNOS-deficient (NOS2(-/-)) mice resolve
      culture-apparent infection in a fashion similar to that of normal control
      (NOS2(+/+)) mice, they sustain significantly increased rates of disease, as
      assessed by hydrosalpinx formation. PCR amplification of ompA followed by
      Southern blot detection of amplicands revealed the presence of chlamydial DNA in
      the lower genital tracts of both NOS2(-/-) and NOS2(+/+) mice at > or =120 days
      postinfection and in upper genital tract tissues at >120 days postinfection.
      However, only NOS2(-/-) mice shed low numbers of viable chlamydiae from the lower
      genital tract after immunosuppressive treatment at 120 days postinfection. When
      cultured primary murine lung fibroblasts were activated in the presence of gamma
      interferon (IFN-gamma), inhibition of chlamydial growth occurred in both
      NOS2(+/+) and NOS2(-/-) cells, but the inhibition was reversible after removal of
      the cytokine in the NOS2(-/-) primary cell culture only. The iNOS-independent
      inhibition was microbistatic but was independent of 2,3-indoleamine dioxygenase
      activity. We conclude that chlamydial DNA and antigens persist in mice subsequent
      to culture-apparent resolution. In addition, IFN-gamma induces in vivo inhibition
      of chlamydial growth through microbistatic mechanisms in the absence of iNOS
      activity, but in the presence of iNOS activity, IFN-gamma is microbicidal and
      effects eradication.

PMID- 11447196
TI  - Enhanced susceptibility to pulmonary infection with Burkholderia cepacia in Cftr(
      /-) mice.
AB  - Progressive pulmonary infection is the dominant clinical feature of cystic
      fibrosis (CF), but the molecular basis for this susceptibility remains
      incompletely understood. To study this problem, we developed a model of chronic
      pneumonia by repeated instillation of a clinical isolate of Burkholderia cepacia
      (genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a
      case of CF into the lungs of Cftr (m1unc-/-) (Cftr(-/-)) and congenic Cftr(+/+)
      controls. Nine days after the last instillation, the CF transmembrane regulator
      knockout mice showed persistence of viable bacteria with chronic severe
      bronchopneumonia while wild-type mice remained healthy. The histopathological
      changes in the lungs of the susceptible Cftr(-/-) mice were characterized by
      infiltration of a mixed inflammatory-cell population into the peribronchiolar and
      perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and
      exudation into alveolar airspaces by a mixed population of macrophages and
      neutrophils. An increased proportion of neutrophils was observed in
      bronchoalveolar lavage fluid from the Cftr(-/-) mice, which, despite an increased
      bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages
      from Cftr(-/-) mice also demonstrated suboptimal activation. These observations
      suggest that the pulmonary host defenses are compromised in lungs from animals
      with CF, as manifested by increased susceptibility to bacterial infection and
      lung injury. This murine model of chronic pneumonia thus reflects, in part, the
      situation in human patients and may help elucidate the mechanisms leading to
      defective host defense in CF.

PMID- 11447197
TI  - Expression of Anaplasma marginale major surface protein 2 variants in
      persistently infected ticks.
AB  - Anaplasma marginale, an intraerythrocytic ehrlichial pathogen of cattle,
      establishes persistent infections in both vertebrate (cattle) and invertebrate
      (tick) hosts. The ability of A. marginale to persist in cattle has been shown to
      be due, in part, to major surface protein 2 (MSP2) variants which are
      hypothesized to emerge in response to the bovine immune response. MSP2 antigenic
      variation has not been studied in persistently infected ticks. In this study we
      analyzed MSP2 in A. marginale populations from the salivary glands of male
      Dermacentor variabilis persistently infected with A. marginale after feeding
      successively on one susceptible bovine and three sheep. New MSP2 variants
      appeared in each A. marginale population, and sequence alignment of the MSP2
      variants revealed multiple amino acid substitutions, insertions, and deletions.
      These results suggest that selection pressure on MSP2 occurred in tick salivary
      glands independent of the bovine immune response.

PMID- 11447198
TI  - Phagocytosis of wild-type Legionella pneumophila occurs through a wortmannin
      insensitive pathway.
AB  - Wild-type Legionella pneumophila grows in human macrophages within a replicative
      phagosome, avoiding lysosomal fusion, while nonreplicative mutants are killed in
      lysosomes. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, blocks
      phagocytosis of an avirulent mutant, but not of wild-type L. pneumophila, without
      affecting membrane ruffling and actin polymerization. These results show that
      wild-type and mutant Legionella strains use different entry pathways. They
      suggest that PI3Ks are involved in phagocytosis of an avirulent L. pneumophila
      mutant and regulate the ability of microorganisms to generate a replicative
      phagosome.

PMID- 11447199
TI  - Localization of surface immunogenic protein on group B streptococcus.
AB  - The localization and accessibility of the group B streptococcus (GBS) surface
      immunogenic protein (Sip) at the surface of intact GBS cells were studied by flow
      cytometric assay and immunogold electron microscopy. Antibodies present in pooled
      sera collected from mice after immunization with purified recombinant Sip
      efficiently recognized native Sip at the surfaces of the different GBS strains
      tested, which included representatives of all nine serotypes. Examination of GBS
      cells by immunogold electron microscopy revealed that the Sip-specific antibodies
      attached preferentially to polar sites and the septal region. This result
      confirmed that Sip is exposed at the intact-cell surface, but it also suggests
      that its distribution is restricted to certain regions of the cell.

PMID- 11447200
TI  - Role of gingipains in growth of Porphyromonas gingivalis in the presence of human
      serum albumin.
AB  - Porphyromonas gingivalis, a bacterium associated with active chronic
      periodontitis lesions, produces several proteolytic enzymes that are thought to
      be involved in host colonization, perturbation of the immune system, and tissue
      destruction. The aim of the present study was to investigate the contribution of
      Arg- and Lys-gingipains produced by P. gingivalis to its growth. Although all of
      the proteins studied were degraded by P. gingivalis, only human serum albumin and
      transferrin supported growth during serial transfers in a chemically defined
      medium (CDM). Growth studies with site-directed gingipain-deficient mutants of P.
      gingivalis revealed that inactivation of both gingipains prevents growth, whereas
      inactivation of either Arg- or Lys-gingipain activity extended the doubling times
      to 33 or 13 h, respectively, compared to 9 h for the parent strain. Growth of the
      mutants and the parent strain was similar when the CDM was supplemented with a
      protein hydrolysate instead of human serum albumin. Incubation of resting P.
      gingivalis ATCC 33277 cells with fluorophore-labeled albumin indicated that the
      proteolytic fragments generated by the gingipains were internalized by the
      bacterial cells. Internalization of fluorophore-labeled albumin fragments was
      reduced or completely inhibited in the proteinase-deficient mutants.
      Interestingly, gingival crevicular fluid samples from diseased periodontal sites
      contained low-molecular-mass albumin fragments, whereas samples from healthy
      sites did not. The critical role of proteinases in the growth of P. gingivalis
      was further investigated using specific Arg- and Lys-gingipain inhibitors. Adding
      the inhibitors to CDM containing albumin revealed that leupeptin (Arg-gingipain A
      and B inhibitor) was more efficient at inhibiting growth than cathepsin B
      inhibitor II (Lys-gingipain inhibitor). Our study suggests that Arg-gingipains
      and, to a lesser extent, Lys-gingipain play an important role in the growth of P.
      gingivalis in a defined medium containing a human protein as the sole carbon and
      nitrogen source.

PMID- 11447201
TI  - Dendritic cells can initiate protective immune responses against malaria.
AB  - An understanding of the antigen presentation mechanisms that mediate induction of
      protective immune responses against malaria is essential for the development of
      successful immunization approaches. Here we show that dendritic cells presenting
      Plasmodium yoelii sporozoite antigens are able to activate specific CD4(+) and
      CD8(+) T cells and initiate protective immune responses against malaria in mice.

PMID- 11447202
TI  - Coupled phase-variable expression and epitope masking of selective surface
      lipoproteins increase surface phenotypic diversity in Mycoplasma hominis.
AB  - A new mechanism expanding mycoplasmal surface diversity is described. Exposure of
      surface epitopes on a constitutively expressed membrane protein (P56) of
      Mycoplasma hominis was subject to high-frequency phase variation due to phase
      variable expression of the P120 antigen and its selective masking of P56
      epitopes. Phase-variable masking may confer previously unrealized adaptive
      capabilities on mycoplasmas.

PMID- 11447203
TI  - Concurrent upregulation of urokinase plasminogen activator receptor and CD11b
      during tuberculosis and experimental endotoxemia.
AB  - Patients with tuberculosis had higher expression of monocyte urokinase receptor
      (uPAR) and CD11b than controls. In vitro, lipoarabinomannan and
      lipopolysaccharide (LPS) from Escherichia coli shared the ability to enhance uPAR
      and CD11b expression on monocytes and granulocytes. In healthy volunteers, LPS
      induced increases in monocyte and granulocyte uPAR and CD11b.

PMID- 11447204
TI  - Effect of low-dose antigen exposure on development of immunity to Helicobacter
      pylori infection in mice.
AB  - The effect of low-dose antigen exposure on the development of immunity to
      Helicobacter pylori infection was studied in outbred mice. Animals that were
      primed with a subinfectious number of H. pylori bacteria exhibited significantly
      lower bacterial loads after challenge with an infectious dose of pathogen (versus
      controls, P < 0.05).

PMID- 11447205
TI  - Interleukin-6 deficiency influences cytokine expression in susceptible BALB mice
      infected with Leishmania major but does not alter the outcome of disease.
AB  - Since interleukin-6 (IL-6) may promote Th2 responses, we infected BALB IL-6
      deficient (IL-6(-/-)) mice with Leishmania major. There was not a significant
      difference between the courses of infection (lesion size and parasite burden) in
      IL-6(-/-) and wild-type mice, but IL-6(-/-) mice expressed lower levels of Th2-
      and Th1-associated cytokines.

PMID- 11447206
TI  - Toxin levels in serum correlate with the development of staphylococcal scalded
      skin syndrome in a murine model.
AB  - Staphylococcal scalded skin syndrome (SSSS) is an exfoliative dermatitis that
      results from infection with exfoliative toxin-producing Staphylococcus aureus.
      SSSS is seen primarily in infants and children. Here we ask if there is a
      specific maturation process that protects healthy adults from this syndrome. For
      these studies, an active recombinant exfoliative toxin A (rETA) was used in a
      neonatal mouse model. A time course generated on the susceptibility to the toxin
      as a function of mouse age indicated that BALB/c mice developed the
      characteristic symptoms of SSSS until day 7 of life. Between day 7 and day 8 of
      life there was a dramatic decrease in susceptibility, such that mice at day 9 of
      life were resistant to the effects of the toxin. This time course corresponds
      approximately to the time needed for maturation of the adaptive immune response,
      and SSSS in adults is often identified with immunocompromised states. Therefore,
      mice deficient in this response were examined. Adult mice thymectomized at birth
      and adult SCID mice did not develop the symptoms of SSSS after injection with the
      toxin, indicating that the adaptive immune response is not responsible for the
      lack of susceptibility observed in the older mice. SSSS in adults is also
      associated with renal disorders, suggesting that levels of toxin in serum are
      important in the development of the disease. rETA was not cleared as efficiently
      from the serum of 1-day-old mice compared to clearance from 10-day-old mice. Ten
      day-old mice were given repeated injections of toxin so that the maximal level of
      toxin was maintained for a sustained period of time, and exfoliation occurred in
      these mice. Thus, whereas the adaptive immune response is not needed for
      protection of adult mice from SSSS, efficient clearance of the toxin from the
      bloodstream is a critical factor.

PMID- 11447207
TI  - Identification and analysis of Staphylococcus aureus components expressed by a
      model system of growth in serum.
AB  - A model system mimicking Staphylococcus aureus bacteremia was developed by growth
      in serum under microaerobic conditions. Eight genes induced by growth in serum
      were identified, including an antimicrobial peptide biosynthesis locus, amino
      acid biosynthetic loci, and genes encoding putative surface proteins. Nine
      independent insertions were found in the major lysine biosynthesis operon, which
      encodes eight genes, is repressed by lysine in vitro, and is expressed in vivo.

PMID- 11447208
TI  - Susceptibility of mice to vaginal infection with Chlamydia trachomatis mouse
      pneumonitis is dependent on the age of the animal.
AB  - Mice from three strains, BALB/c (H-2(d)), C3H (H-2(k)), and C57BL/6 (H-2(b)),
      ranging from 5 to 14 weeks of age, were inoculated intravaginally with different
      doses of the Chlamydia trachomatis mouse pneumonitis serovar. Vaginal swabs taken
      at weekly intervals showed that the percentage of animals with positive cultures
      and the number of inclusion-forming units recovered per mouse were higher in the
      younger animals. Furthermore, vaginal shedding lasted longer in the young mice
      than in the older mice. In addition, following mating higher rates of infertility
      and a decrease in the number of embryos were observed in the infected young mice.
      In conclusion, susceptibility to a chlamydial vaginal infection is dependent on
      the age of the mice, with the older animals being more resistant.

PMID- 11447209
TI  - Evolutionary relationships among virulence-associated histidine kinases.
AB  - A strong relationship between virulence-associated sensor histidine kinases of
      fungi and those in Streptomyces coelicolor was observed, and phylogenetic
      analysis suggested that bacterium-to-eukaryote horizontal gene transfer had
      occurred between ancestors of these organisms. Phylogenetic analysis also
      identified a group of histidine kinases orthologous to the Streptomyces proteins
      that includes Pseudomonas aeruginosa GacS. We provide evidence that GacS is
      important for swarming motility, lipase production, and virulence in mice and had
      evolved to have partial functional overlaps with PhoQ, a less-related virulence
      associated histidine kinase.

PMID- 11447210
TI  - Mannan-binding lectin enhances susceptibility to visceral leishmaniasis.
AB  - Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated
      with the probability of developing visceral leishmaniasis. Monocytes infected
      with MBL-opsonized Leishmania chagasi promastigotes secreted higher levels of
      tumor necrosis factor alpha and interleukin-6 than cells infected with
      nonopsonized parasites. Our findings indicate that MBL can modulate the clinical
      outcome of infection with L. chagasi and the function of infected macrophages.

PMID- 11447211
TI  - The top loops of the C(2) domains from synaptotagmin and phospholipase A(2)
      control functional specificity.
AB  - The phospholipid-binding specificities of C(2) domains, widely distributed Ca(2+)
      binding modules, differ greatly despite similar three-dimensional structures. To
      understand the molecular basis for this specificity, we have examined the
      synaptotagmin 1 C(2)A domain, which interacts in a primarily electrostatic,
      Ca(2+)-dependent reaction with negatively charged phospholipids, and the
      cytosolic phospholipase A(2) (cPLA(2)) C(2) domain, which interacts by a
      primarily hydrophobic Ca(2+)-dependent mechanism with neutral phospholipids. We
      show that grafting the short Ca(2+)-binding loops from the tip of the cPLA(2)
      C(2) domain onto the top of the synaptotagmin 1 C(2)A domain confers onto the
      synaptotagmin 1 C(2)A domain the phospholipid binding specificity of the cPLA(2)
      C(2) domain, indicating that the functional specificity of C(2) domains is
      determined by their short top loops.

PMID- 11447212
TI  - Interaction of farnesylated PRL-2, a protein-tyrosine phosphatase, with the beta
      subunit of geranylgeranyltransferase II.
AB  - Protein of regenerating liver (PRL)-1, -2, and -3 comprise a subgroup of closely
      related protein-tyrosine phosphatases featuring a C-terminal prenylation motif
      conforming to either the consensus sequence for farnesylation, CAAX, or
      geranylgeranylation, CCXX. Yeast two-hybrid screening for PRL-2-interacting
      proteins identified the beta-subunit of Rab geranylgeranyltransferase II (betaGGT
      II). The specific interaction of betaGGT II with PRL-2 but not with PRL-1 or -3
      occurred in yeast and HeLa cells. Chimeric PRL-1/-2 molecules were tested for
      their interaction with betaGGT II, and revealed that the C-terminal region of PRL
      2 is required for interaction, possibly the PRL variable region immediately
      preceeding the CAAX box. Additionally, PRL-2 prenylation is prequisite for
      betaGGT II binding. As prenylated PRL-2 is localized to the early endosome, we
      propose that this is where the interaction occurs. PRL-2 is not a substrate for
      betaGGT II, as isoprenoid analysis showed that PRL-2 was solely farnesylated in
      vivo. Co-expression of the alpha-subunit (alpha) of GGT II, betaGGT II, and PRL-2
      resulted in alpha/betaGGT II heterodimer formation and prevented PRL-2 binding.
      Expression of PRL-2 alone inhibited the endogenous alpha/betaGGT II activity in
      HeLa cells. Together, these results indicate that the binding of alphaGGT II and
      PRL-2 to betaGGT II is mutually exclusive, and suggest that PRL-2 may function as
      a regulator of GGT II activity.

PMID- 11447213
TI  - 15-lipoxygenase-1 metabolites down-regulate peroxisome proliferator-activated
      receptor gamma via the MAPK signaling pathway.
AB  - Human colon tumors have elevated levels of 15-lipoxygenase-1 (15-LO-1),
      suggesting that 15-LO-1 may play a role in the development of colorectal cancer.
      Also, 15-LO-1 metabolites can up-regulate epidermal growth factor signaling
      pathways, which results in an increase in mitogenesis. However, metabolites of 15
      LO-1 can serve as ligands for peroxisome proliferator-activated receptor gamma
      (PPARgamma), and activation of this receptor causes most colon cancer cell lines
      to undergo a differentiative response and reverse their malignant phenotype.
      Hence, the role 15-LO-1 plays in colon cancer is not clear. To clarify the role
      of 15-LO-1 in carcinogenesis, the effect of 15-LO-1 and its metabolites on
      epidermal growth factor signaling and PPARgamma was investigated. In HCT-116
      cells, exogenously added 15-LO-1 metabolites, 13-(S)-hydroxyoctadecadienoic acid,
      13-(R)-hydroxyoctadecadienoic acid, and 13-(S)-hydroperoxyoctadecadienoic acid,
      up-regulated the MAPK signaling pathway, and an increase in PPARgamma
      phosphorylation was observed. Furthermore, in stable overexpressing 15-LO-1 HCT
      116 cells, which produce endogenous 15-LO-1 metabolites, an up-regulation in
      mitogen-activated protein kinase and PPARgamma phosphorylation was observed.
      Incubation with a MAPK inhibitor ablated MAPK and PPARgamma phosphorylation. The
      15-LO-1 up-regulates MAPK activity and increases PPARgamma phosphorylation,
      resulting in a down-regulation of PPARgamma activity. Thus, 15-LO-1 metabolites
      may not only serve as ligands for PPARgamma but can down-regulate PPARgamma
      activity via the MAPK signaling pathway.

PMID- 11447214
TI  - Homocysteine induces programmed cell death in human vascular endothelial cells
      through activation of the unfolded protein response.
AB  - Severe hyperhomocysteinemia is associated with endothelial cell injury that may
      contribute to an increased incidence of thromboembolic disease. In this study,
      homocysteine induced programmed cell death in human umbilical vein endothelial
      cells as measured by TdT-mediated dUTP nick end labeling assay, DNA ladder
      formation, induction of caspase 3-like activity, and cleavage of procaspase 3.
      Homocysteine-induced cell death was specific to homocysteine, was not mediated by
      oxidative stress, and was mimicked by inducers of the unfolded protein response
      (UPR), a signal transduction pathway activated by the accumulation of unfolded
      proteins in the lumen of the endoplasmic reticulum. Dominant negative forms of
      the endoplasmic reticulum-resident protein kinases IRE1alpha and -beta, which
      function as signal transducers of the UPR, prevented the activation of glucose
      regulated protein 78/immunoglobulin chain-binding protein and C/EBP homologous
      protein/growth arrest and DNA damage-inducible protein 153 in response to
      homocysteine. Furthermore, overexpression of the point mutants of IRE1 with
      defective RNase more effectively suppressed the cell death than the kinase
      defective mutant. These results indicate that homocysteine induces apoptosis in
      human umbilical vein endothelial cells by activation of the UPR and is signaled
      through IRE1. The studies implicate that the UPR may cause endothelial cell
      injury associated with severe hyperhomocysteinemia.

PMID- 11447215
TI  - ldhc expression in non-germ cell nuclei is repressed by NF-I binding.
AB  - Developmental and testis-specific expression of the mouse lactate dehydrogenase C
      (mldhc) gene requires mechanisms for activation in germ cells and repression in
      somatic cells. Promoter activity restricted to the testis has been demonstrated
      using in vitro transcription assays with a 60-base pair promoter sequence
      upstream of the transcription initiation site. This promoter fragment has a TATA
      box and an overlapping 31-base pair palindromic sequence. Here we have explored
      the role of the palindrome as a silencer of the ldhc gene in somatic tissues. A
      gel retardation assay detected two sites within the palindrome that were
      important for protein binding. A member of the NF-I/CTF family was identified as
      the protein binding to one of the sites. In transiently transfected mouse L
      cells, a promoter fragment in which the NF-I site was mutated showed a 4-fold
      greater activity as compared with the wild-type sequence. Overexpression of the
      four NF-I proteins, NF-IA, -B, -C, or -X, in mouse L cells transiently
      transfected with an ldhc promoter-reporter construct resulted in a 20-50%
      decrease in activity of the wild-type promoter but had no effect when the NF-I
      binding element in the palindrome was mutated. These results indicate a role for
      the NF-I proteins in regulation of the mldhc gene.

PMID- 11447216
TI  - Inhibition of translocation of beta -lactamase into the yeast endoplasmic
      reticulum by covalently bound benzylpenicillin.
AB  - We found recently that beta-lactamase folds in the yeast cytosol to a native
      like, catalytically active, and trypsin-resistant conformation, and is thereafter
      translocated into the ER and secreted to the medium. Previously, it was thought
      that pre-folded proteins cannot be translocated. Here we have studied in living
      yeast cells whether beta-lactamase, a tight globule in authentic form, must be
      unfolded for ER translocation. A beta-lactamase mutant (E166A) binds irreversibly
      benzylpenicillin via Ser(70) in the active site. We fused E166A to the C terminus
      of a yeast-derived polypeptide having a post-translational signal peptide. In the
      presence of benzylpenicillin, the E166A fusion protein was not translocated into
      the endoplasmic reticulum, whereas translocation of the unmutated variant was not
      affected. The benzylpenicillin-bound protein adhered to the endoplasmic reticulum
      membrane, where it prevented translocation of BiP, carboxypeptidase Y, and
      secretory proteins. Although the 321-amino acid-long N-terminal fusion partner
      adopts no regular secondary structure and should have no constraints for pore
      penetration, the benzylpenicillin-bound protein remained fully exposed to the
      cytosol, maintaining its signal peptide. Our data suggest that the beta-lactamase
      portion must unfold for translocation, that the unfolding machinery is cytosolic,
      and that unfolding of the remote C-terminal beta-lactamase is required for
      initiation of pore penetration.

PMID- 11447217
TI  - Suppression of chemically induced apoptosis but not necrosis of renal proximal
      tubular epithelial (LLC-PK1) cells by focal adhesion kinase (FAK). Role of FAK in
      maintaining focal adhesion organization after acute renal cell injury.
AB  - Decreased phosphorylation of focal adhesion kinase (FAK) is associated with loss
      of focal adhesions and actin stress fibers and precedes the onset of apoptosis in
      renal epithelial cells caused by nephrotoxicants (Van de Water, B., Nagelkerke,
      J. F., and Stevens, J. L. (1999) J. Biol. Chem. 274, 13328-13337). The role of
      FAK in the control of apoptosis caused by nephrotoxicants was further
      investigated in LLC-PK1 cells that were stably transfected with either green
      fluorescent protein (GFP)-FAK or dominant negative acting deletion mutants of
      FAK, GFP-FAT, and GFP-FRNK. GFP-FAT and GFP-FRNK delayed the formation of focal
      adhesions and prevented the localization of endogenous (phosphorylated) FAK at
      these sites. GFP-FAT and GFP-FRNK overexpression potentiated the onset of
      apoptosis caused by the nephrotoxicant dichlorovinyl-cysteine. This was
      associated with an increased activation of caspase-3. GFP-FAT also potentiated
      apoptosis caused by doxorubicin but not cisplatin. The potentiation of apoptosis
      by GFP-FAT was related to an almost complete dephosphorylation of FAK; this did
      not occur in cells overexpressing only GFP. This dephosphorylation was associated
      with a pronounced loss of focal adhesion organization in GFP-FAT cells, in
      association with loss of tyrosine phosphorylation of paxillin. In conclusion, the
      data indicate an important role of cell-matrix signaling in the control of
      chemically induced apoptosis; loss of FAK activity caused by toxic chemicals
      results in perturbations of focal adhesion organization with a subsequent
      inactivation of associated (signaling) molecules and loss of survival signaling.

PMID- 11447218
TI  - Global gene expression analysis reveals a role for the alpha 1 integrin in renal
      pathogenesis.
AB  - Kidney fibrosis is the hallmark of most types of progressive kidney disease,
      including the genetic disorder Alport's syndrome. We undertook gene expression
      analysis in Alport's syndrome mouse kidneys using microchip arrays to
      characterize the development of fibrosis. In addition to matrix and matrix
      remodeling genes, consistent with interstitial fibrosis, macrophage-related genes
      show elevated expression levels in Alport's syndrome kidneys. Immunohistochemical
      analysis of kidney sections illustrated that macrophages as well as
      myofibroblasts accumulate in the tubular interstitium. Deletion of alpha(1)
      integrin results in decreased accumulation of both myofibroblasts and macrophages
      in the tubular interstitium in Alport's syndrome mice and delays disease
      progression. Transforming growth factor beta antagonism, although reducing
      interstitial fibrosis, does not limit macrophage accumulation in the tubular
      interstitium and disease progression. In this study, we identified previously
      overlooked inflammatory events that occur in the tubulointerstitial region. We
      propose that in addition to the previously suggested role for the alpha(1)beta(1)
      integrin in mesangial expansion and abnormal laminin deposition, this integrin
      may be critical for monocyte accumulation that, in turn, may lead directly to
      renal failure. Our gene expression and immunohistochemical data indicate that
      macrophage accumulation is dependent on alpha(1) integrin expression on the
      macrophage cell surface and that anti-alpha(1) integrin strategies may be
      employed as therapeutics in the treatment of chronic inflammatory and fibrotic
      diseases.

PMID- 11447219
TI  - Residues at the active site of the esterase 2 from Alicyclobacillus
      acidocaldarius involved in substrate specificity and catalytic activity at high
      temperature.
AB  - The recently solved three-dimensional structure of the thermophilic esterase 2
      from Alicyclobacillus acidocaldarius allowed us to have a snapshot of an enzyme
      sulfonate complex, which mimics the second stage of the catalytic reaction,
      namely the covalent acyl-enzyme intermediate. The aim of this work was to design,
      by structure-aided analysis and to generate by site-directed and saturation
      mutagenesis, EST2 variants with changed substrate specificity in the direction of
      preference for monoacylesters whose acyl-chain length is greater than eight
      carbon atoms. Positions 211 and 215 of the polypeptide chain were chosen to
      introduce mutations. Among five variants with single and double amino acid
      substitutions, three were obtained, M211S, R215L, and M211S/R215L, that changed
      the catalytic efficiency profile in the desired direction. Kinetic
      characterization of mutants and wild type showed that this change was achieved by
      an increase in k(cat) and a decrease in K(m) values with respect to the parental
      enzyme. The M211S/R215L specificity constant for p-nitrophenyl decanoate
      substrate was 6-fold higher than the wild type. However, variants M211T, M211S,
      and M211V showed strikingly increased activity as well as maximal activity with
      monoacylesters with four carbon atoms in the acyl chain, compared with the wild
      type. In the case of mutant M211T, the k(cat) for p-nitrophenyl butanoate was 2.4
      fold higher. Overall, depending on the variant and on the substrate, we observed
      improved catalytic activity at 70 degrees C with respect to the wild type, which
      was a somewhat unexpected result for an enzyme with already high k(cat) values at
      high temperature. In addition, variants with altered specificity toward the acyl
      chain length were obtained. The results were interpreted in the context of the
      EST2 three-dimensional structure and a proposed catalytic mechanism in which
      k(cat), e.g. the limiting step of the reaction, was dependent on the acyl chain
      length of the ester substrate.

PMID- 11447220
TI  - Mutational analysis at Asn-41 in peanut agglutinin. A residue critical for the
      binding of the tumor-associated Thomsen-Friedenreich antigen.
AB  - Peanut agglutinin is a clinically important lectin due to its application in the
      screening of mature and immature thymocytes as well as in the detection of
      cancerous malignancies. The basis for these applications is the remarkably strong
      affinity of the lectin for the tumor-associated Thomsen-Friedenreich antigen (T
      antigen) and more so due to its ability to distinguish T-antigen from its cryptic
      forms. The crystal structure of the complex of peanut agglutinin with T-antigen
      reveals the basis of this specificity. Among the contacts involved in providing
      this specificity toward T-antigen is the water-mediated interaction between the
      side chain of Asn-41 and the carbonyl oxygen of the acetamido group of the second
      hexopyranose ring of the sugar molecule. Site-directed mutational changes were
      introduced at this residue with the objective of probing the role of this residue
      in T-antigen binding and possibly engineering an altered species with increased
      specificity for T-antigen. Of the three mutants tested, i.e. N41A, N41D, and
      N41Q, the last one shows improved potency for recognition of T-antigen. The
      affinities of the mutants can be readily explained on the basis of the crystal
      structure of the complex and simple modeling. In particular, the change of
      asparagine to glutamine could lead to a direct interaction of the side chain with
      the sugar while at the same time retaining the water bridge. This study
      strengthens the theory that in lectins the nonprimary contacts generally made
      through water bridges are involved in imparting exquisite specificity.

PMID- 11447221
TI  - Biological function and cellular mechanism of bone morphogenetic protein-6 in the
      ovary.
AB  - The process of ovarian folliculogenesis is composed of proliferation and
      differentiation of the constitutive cells in developing follicles. Growth factors
      emitted by oocytes integrate and promote this process. Growth differentiation
      factor-9 (GDF-9), bone morphogenetic protein (BMP)-15, and BMP-6 are oocyte
      derived members of the transforming growth factor-beta superfamily. In contrast
      to the recent studies on GDF-9 and BMP-15, nothing is known about the biological
      function of BMP-6 in the ovary. Here we show that, unlike BMP-15 and GDF-9, BMP-6
      lacks mitogenic activity on rat granulosa cells (GCs) and produces a marked
      decrease in follicle-stimulating hormone (FSH)-induced progesterone (P(4)) but
      not estradiol (E(2)) production, demonstrating not only the first identification
      of GCs as BMP-6 targets in the ovary but also its selective modulation of FSH
      action in steroidogenesis. This BMP-6 activity resembles BMP-15 but differs from
      GDF-9 activities. BMP-6 also exhibited similar action to BMP-15 by attenuating
      the steady state mRNA levels of FSH-induced steroidogenic acute regulatory
      protein (StAR) and P450 side-chain cleavage enzyme (P450scc), without affecting
      P450 aromatase mRNA level, supporting its differential function on FSH-regulated
      P(4) and E(2) production. However, unlike BMP-15, BMP-6 inhibited forskolin- but
      not 8-bromo-cAMP-induced P(4) production and StAR and P450scc mRNA expression.
      BMP-6 also decreased FSH- and forskolin-stimulated cAMP production, suggesting
      that the underlying mechanism by which BMP-6 inhibits FSH action most likely
      involves the down-regulation of adenylate cyclase activity. This is clearly
      distinct from the mechanism of BMP-15 action, which causes the suppression of
      basal FSH receptor (FSH-R) expression, without affecting adenylate cyclase
      activity. As assumed, BMP-6 did not alter basal FSH-R mRNA levels, whereas it
      inhibited FSH- and forskolin- but not 8-bromo-cAMP-induced FSH-R mRNA
      accumulation. These studies provide the first insight into the biological
      function of BMP-6 in the ovary and demonstrate its unique mechanism of regulating
      FSH action.

PMID- 11447222
TI  - A role for mitochondrial Bak in apoptotic response to anticancer drugs.
AB  - In the present study a clonal Jurkat cell line deficient in expression of Bak was
      used to analyze the role of Bak in cytochrome c release from mitochondria. The
      Bak-deficient T leukemic cells were resistant to apoptosis induced by UV,
      staurosporin, VP-16, bleomycin, or cisplatin. In contrast to wild type Jurkat
      cells, these Bak-deficient cells did not respond to UV or treatment with these
      anticancer drugs by membranous phosphatidylserine exposure, DNA breaks,
      activation of caspases, or release of mitochondrial cytochrome c. The block in
      the apoptotic cascade was in the mitochondrial mechanism for cytochrome c release
      because purified mitochondria from Bak-deficient cells failed to release
      cytochrome c or apoptosis-inducing factor in response to recombinant Bax or
      truncated Bid. The resistance of Bak-deficient cells to VP-16 was reversed by
      transduction of the Bak gene into these cells. Also, the cytochrome c releasing
      capability of the Bak-deficient mitochondria was restored by insertion of
      recombinant Bak protein into purified mitochondria. Following mitochondrial
      localization, low dose recombinant Bak restored the mitochondrial release of
      cytochrome c in response to Bax; at increased doses it induced cytochrome c
      release itself. The function of Bak is independent of Bid and Bax because
      recombinant Bak induced cytochrome c release from mitochondria purified from Bax(
      /-), Bid(-/-), or Bid(-/-) Bax(-/-) mice. Together, our findings suggest that Bak
      plays a key role in the apoptotic machinery of cytochrome c release and thus in
      the chemoresistance of human T leukemic cells.

PMID- 11447223
TI  - Angiopoietin-1, unlike angiopoietin-2, is incorporated into the extracellular
      matrix via its linker peptide region.
AB  - Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) affect angiogenesis differently
      during embryogenesis and tumorigenesis. In an attempt to understand the molecular
      basis underlying the distinct roles of those two homologous molecules, we
      investigated the association of Ang-1 and Ang-2 with the extracellular matrix
      (ECM). TA3 murine mammary carcinoma (TA3) and Lewis lung carcinoma cells
      expressing v5 epitope-tagged Ang-1 and Ang-2 were used in our studies. The
      results indicated that Ang-1 is secreted and incorporated into the ECM of the
      tumor cells, whereas Ang-2 is not associated with the ECM. The mutagenesis study
      indicated the domain that is responsible for the ECM association of Ang-1 is the
      linker peptide region between the coiled-coil and the fibrinogen-like domains. A
      weak binding between the coiled-coil domain of Ang-1 and the ECM was observed.
      Immunocytochemistry study revealed a distinct ECM distribution pattern of Ang-1,
      which is quite different from that of fibronectin, laminin, and collagen types I
      and IV. The ECM-associated Ang-1 proteins are released, and Tie-2 receptors are
      phosphorylated upon the adhesion of human umbilical vein endothelial cells.
      Implications of the difference in the ECM association of Ang-1 and Ang-2, which
      are related to the regulation of angiopoietin activity and their roles in local
      versus distant angiogenesis during tumor metastasis, are discussed.

PMID- 11447224
TI  - Tetrahydrobiopterin scavenges superoxide in dopaminergic neurons.
AB  - Increased oxidative stresses are implicated in the pathogenesis of Parkinson's
      disease, and dopaminergic neurons may be intrinsically susceptible to oxidative
      damage. However, the selective presence of tetrahydrobiopterin (BH(4)) makes
      dopaminergic neurons more resistant to oxidative stress caused by glutathione
      depletion. To further investigate the mechanisms of BH(4) protection, we examined
      the effects of BH(4) on superoxide levels in individual living mesencephalic
      neurons. Dopaminergic neurons have intrinsically lower levels of superoxide than
      nondopaminergic neurons. In addition, inhibiting BH(4) synthesis increased
      superoxide in dopaminergic neurons, while BH(4) supplementation decreased
      superoxide in nondopaminergic cells. BH(4) is also a cofactor in catecholamine
      and NO production. In order to exclude the possibility that the antioxidant
      effects of BH(4) are mediated by dopamine and NO, we used fibroblasts in which
      neither catecholamine nor NO production occurs. In fibroblasts, BH(4) decreased
      baseline reactive oxygen species, and attenuated reactive oxygen species increase
      by rotenone and antimycin A. Physiologic concentrations of BH(4) directly
      scavenged superoxide generated by potassium superoxide in vitro. We hypothesize
      that BH(4) protects dopaminergic neurons from ordinary oxidative stresses
      generated by dopamine and its metabolites and that environmental insults or
      genetic defects may disrupt this intrinsic capacity of dopaminergic neurons and
      contribute to their degeneration in Parkinson's disease.

PMID- 11447225
TI  - Reactive oxygen species-induced phosphorylation of p53 on serine 20 is mediated
      in part by polo-like kinase-3.
AB  - Upon exposure of cells to hydrogen peroxide (H(2)O(2)) phosphorylation of p53 was
      rapidly induced in human fibroblast GM00637, and this phosphorylation occurred on
      serine 9, serine 15, serine 20, but not on serine 392. In addition, H(2)O(2)
      induced phosphorylation of p53 was followed by induction of p21, suggesting
      functional activation of p53. Induction of phosphorylation of p53 on multiple
      serine residues by H(2)O(2) was caffeine-sensitive and blocked in ATM(-/-) cells.
      Polo-like kinase-3 (Plk3) activity was also activated upon H(2)O(2) treatment,
      and this activation was ATM-dependent. Recombinant His(6)-Plk3 phosphorylated
      glutathione S-transferase (GST)-p53 fusion protein but not GST alone. When
      phoshorylated in vitro by His(6)-Plk3, but not by the kinase-defective mutant
      His6-Plk3(K52R), GST-p53 was recognized by an antibody specifically to serine 20
      phosphorylated p53, indicating that serine 20 is an in vitro target of Plk3. Also
      serine 20-phosphorylated p53 was coimmunoprecipitated with Plk3 in cells treated
      with H(2)O(2). Furthermore, although H(2)O(2) strongly induced serine 15
      phosphorylation of p53, it failed to induce serine 20 phosphorylation in Plk3
      dificient Daudi cells. Ectopic expression of a Plk3 dominant negative mutant,
      Plk3(K52R), in GM00637 cells suppressed H(2)O(2)-induced serine 20
      phosphorylation. Taken together, our studies strongly suggest that the oxidative
      stress-induced activation of p53 is at least in part mediated by Plk3.

PMID- 11447226
TI  - Cloning of a novel retinoid-inducible serine carboxypeptidase from vascular
      smooth muscle cells.
AB  - Retinoids block smooth muscle cell (SMC) proliferation and attenuate neointimal
      formation after vascular injury, presumably through retinoid receptor-mediated
      changes in gene expression. To identify target genes in SMC whose encoded
      proteins could contribute to such favorable biological effects, we performed a
      subtractive screen for retinoid-inducible genes in cultured SMC. Here, we report
      on the cloning and initial characterization of a novel retinoid-inducible serine
      carboxypeptidase (RISC). Expression of RISC is low in cultured SMC but
      progressively increases over a 5-day time-course treatment with all-trans
      retinoic acid. A near full-length rat RISC cDNA was cloned and found to have a
      452-amino acid open reading frame containing an amino-terminal signal sequence,
      followed by several conserved domains comprising the catalytic triad common to
      members of the serine carboxypeptidase family. In vitro transcription and
      translation experiments showed that the rat RISC cDNA generates an approximately
      51-kDa protein. Confocal immunofluorescence microscopy of COS-7 cells transiently
      transfected with a RISC-His tag plasmid revealed cytosolic localization of the
      fusion protein. Western blotting studies using conditioned medium from
      transfected COS-7 cells suggest that RISC is a secreted protein. Tissue Northern
      blotting studies demonstrated robust expression of RISC in rat aorta, bladder,
      and kidney with much lower levels in all other tissues analyzed; high level RISC
      expression was also observed in human kidney. In situ hybridization verified the
      localization of RISC to medial SMC of the adult rat aorta. Interestingly,
      expression in kidney was restricted to proximal convoluted tubules; little or no
      expression was observed in glomerular cells, distal convoluted and collecting
      tubules, or medullary cells. Radiation hybrid mapping studies placed the rat RISC
      locus on chromosome 10q. These studies reveal a novel retinoid-inducible protease
      whose activity may be involved in vascular wall and kidney homeostasis.

PMID- 11447227
TI  - Properties and regulation of organic cation transport in freshly isolated human
      proximal tubules.
AB  - The kidney, and more specifically the proximal tubule, is the main site of
      elimination of cationic endogenous metabolites and xenobiotics. Although numerous
      studies exist on renal organic cation transport of rat and rabbit, no information
      is available from humans. Therefore, we examined organic cation transport and its
      regulation across the basolateral membrane of isolated human proximal tubules.
      mRNA for the cation transporters hOCT1 and hOCT2 as well as hOCTN1 and hOCTN2 was
      detected in these tubules. Organic cation transport across the basolateral
      membrane of isolated collapsed proximal tubules was recorded with the fluorescent
      dye 4-(4-dimethylamino)styryl-N-methylpyridinium (ASP(+)). Depolarization of the
      cells by rising extracellular K(+) concentration to 145 mm reduced ASP(+) uptake
      by 20 +/- 5% (n = 15), indicating its electrogeneity. The substrates of organic
      cation transport tetraethylammonium (K(i) = 63 microm) and cimetidine (K(i) = 11
      microm) as well as the inhibitor quinine (K(i) = 2.9 microm) reduced ASP(+)
      uptake concentration dependently. Maximal inhibition reached with these
      substances was approximately 60%. Stimulation of protein kinase C with 1,2
      dioctanoyl-sn-glycerol (DOG, 1 microm) or ATP (100 microm) inhibited ASP(+)
      uptake by 30 +/- 3 (n = 16) and 38 +/- 13% (n = 6), respectively. The effect of
      DOG could be reduced with calphostin C (0.1 microm, n = 7). Activation of
      adenylate cyclase by forskolin (1 microm) decreased ASP(+) uptake by 29 +/- 3% (n
      = 10). hANP (10 nm) or 8-bromo-cGMP (100 microm) also decreased ASP(+) uptake by
      17 +/- 3 (n = 9) or 32 +/- 5% (n = 10), respectively. We show for the first time
      that organic cation transport across the basolateral membrane of isolated human
      proximal tubules, most likely mediated via hOCT2, is electrogenic and regulated
      by protein kinase C, the cAMP- and the cGMP-dependent protein kinases.

PMID- 11447228
TI  - Identification of a ligand-binding site in the Na+/bile acid cotransporting
      protein from rabbit ileum.
AB  - Reabsorption of bile acids occurs in the terminal ileum by a Na(+)-dependent
      transport system composed of several subunits of the ileal bile acid transporter
      (IBAT) and the ileal lipid-binding protein. To identify the bile acid-binding
      site of the transporter protein IBAT, ileal brush border membrane vesicles from
      rabbit ileum were photoaffinity labeled with a radioactive 7-azi-derivative of
      cholyltaurine followed by enrichment of IBAT protein by preparative SDS gel
      electrophoresis. Enzymatic fragmentation with chymotrypsin yielded IBAT peptide
      fragments in the molecular range of 20.4-4 kDa. With epitope-specific antibodies
      generated against the C terminus a peptide of molecular mass of 6.6-7 kDa was
      identified as the smallest peptide fragment carrying both the C terminus and the
      covalently attached radiolabeled bile acid derivative. This clearly indicates
      that the ileal Na(+)/bile acid cotransporting protein IBAT contains a bile acid
      binding site within the C-terminal 56-67 amino acids. Based on the seven
      transmembrane domain model for IBAT, the bile acid-binding site is localized to a
      region containing the seventh transmembrane domain and the cytoplasmic C
      terminus. Alternatively, assuming the nine-transmembrane domain model, this bile
      acid-binding site is localized to the ninth transmembrane domain and the C
      terminus.

PMID- 11447229
TI  - Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug
      resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine.
AB  - Human multidrug resistance protein 4 (MRP4) has recently been determined to
      confer resistance to the antiviral purine analog 9-(2
      phosphonylmethoxyethyl)adenine and methotrexate. However, neither its substrate
      selectivity nor physiological functions have been determined. Here we report the
      results of investigations of the in vitro transport properties of MRP4 using
      membrane vesicles prepared from insect cells infected with MRP4 baculovirus. It
      is shown that expression of MRP4 is specifically associated with the MgATP
      dependent transport of cGMP, cAMP, and estradiol 17-beta-D-glucuronide (E(2)17
      beta G). cGMP, cAMP, and E(2)17 beta G are transported with K(m) and V(max)
      values of 9.7 +/- 2.3 microm and 2.0 +/- 0.3 pmol/mg/min, 44.5 +/- 5.8 microm and
      4.1 +/- 0.4 pmol/mg/min, and 30.3 +/- 6.2 microm and 102 +/- 16 pmol/mg/min,
      respectively. Consistent with its ability to transport cyclic nucleotides, it is
      demonstrated that the MRP4 drug resistance profile extends to 6-mercaptopurine
      and 6-thioguanine, two anticancer purine analogs that are converted in the cell
      to nucleotide analogs. On the basis of its capacity to transport cyclic
      nucleotides and E(2)17 beta G, it is concluded that MRP4 may influence diverse
      cellular processes regulated by cAMP and cGMP and that its substrate range is
      distinct from that of any other characterized MRP family member.

PMID- 11447230
TI  - Serine 132 is the C3 covalent attachment point on the CH1 domain of human IgG1.
AB  - The covalent binding of C3 (complement component C3) to antigen-antibody
      complexes (Ag.Ab; immune complexes (ICs)) is a key event in the uptake,
      transport, presentation, and elimination of Ag in the form of Ag.Ab.C3b (IC.C3b).
      Upon interaction of C3 with IgG.IC, C3b.C3b.IgG covalent complexes are formed
      that are detected on SDS-polyacrylamide gel electrophoresis by two bands
      corresponding to C3b.C3b (band A) and C3b.IgG (band B) covalent complexes. This
      allows one to evaluate the covalent binding of C3b to IgG antibodies. It has been
      described that C3b can attach to both the Fab (on the CH1 domain) and the Fc
      regions of IgG. Here the covalent interaction of C3b to the CH1 domain, a region
      previously described spanning residues 125-147, has been studied. This region of
      the CH1 domain is exposed to solvent and contains a cluster of six potential
      acceptor sites for ester bond formation with C3b (four Ser and two Thr). A set of
      10 mutant Abs were generated with the putative acceptor residues substituted by
      Ala, and we studied their covalent interaction with C3b. Single (Ser-131, Ser
      132, Ser-134, Thr-135, Ser-136, and Thr-139), double (positions 131-132), and
      multiple (positions 134-135-136, 131-132-134-135-136, and 131-132-134-135-136
      139) mutants were produced. None of the mutants (single, double, or multiple)
      abolished completely the ability of IgG to bind C3b, indicating the presence of
      C3b binding regions other than in the CH1 domain. However, all mutant Abs, in
      which serine at position 132 was replaced by Ala, showed a significant decrease
      in the ability to form C3b.IgG covalent complexes, whereas the remaining mutants
      had normal activity. In addition we examined ICs using the F(ab')2 fragment of
      the mutant Abs, and only those containing Ala at position 132 (instead of Ser)
      failed to bind C3b. Thus Ser-132 is the binding site for C3b on the CH1 domain of
      the heavy chain, in the Fab region of human IgG.

PMID- 11447231
TI  - Intracellular delivery of proteins with a new lipid-mediated delivery system.
AB  - There are many very effective methods to introduce transcriptionally active DNA
      into viable cells but approaches to deliver functional proteins are limited. We
      have developed a lipid-mediated delivery system that can deliver functional
      proteins or other bioactive molecules into living cells. This delivery system is
      composed of a new trifluoroacetylated lipopolyamine (TFA-DODAPL) and dioleoyl
      phosphatidylethanolamine (DOPE). This cationic formulation successfully delivered
      antibodies, dextran sulfates, phycobiliproteins, albumin, and enzymes (beta
      galactosidase and proteases) into the cytoplasm of numerous adherent and
      suspension cells. Two systems were used to demonstrate that the proteins were
      delivered in a functionally active form. First, intracellular beta-galactosidase
      activity was clearly demonstrated within X-gal-stained cells after TFA
      DODAPL:DOPE-mediated delivery of the enzyme. Second, the delivery system mediated
      delivery of several caspases (caspase 3, caspase 8, and granzyme B) into cultured
      cell lines and primary cells triggering apoptosis. Mechanistic studies showed
      that up to 100% of the protein mixed with the lipid formulation was captured into
      a lipid-protein complex, and up to 50% of the input protein associated with
      cells. This lipid-mediated transport system makes protein delivery into cultured
      cells as convenient, effective, and reliable as DNA transfection.

PMID- 11447232
TI  - Sp3 represses the Sp1-mediated transactivation of the human COL2A1 gene in
      primary and de-differentiated chondrocytes.
AB  - Sp1 and Sp3 effects on the transcription of the human alpha1(II) procollagen gene
      (COL2A1) were investigated in both differentiated and de-differentiated rabbit
      articular chondrocytes. Transient transfection with constructs of deleted COL2A1
      promoter sequences driving the luciferase reporter gene revealed that the region
      spanning -266 to +121 base pairs showed Sp1-enhancing effects, whatever the
      differentiation state. In contrast, Sp3 did not influence COL2A1 gene
      transcription. Concomitant overexpression of the two Sp proteins demonstrated
      that Sp3 blocked the Sp1 induction of COL2A1 promoter activity. Moreover,
      inhibition of Sp1/Sp3 binding to their target DNA sequence decreased both COL2A1
      gene transcription and Sp1-enhancing effects. DNase I footprinting and gel
      retardation assays revealed that Sp1 and Sp3 bind specifically to cis-sequences
      of the COL2A1 gene promoter whereby they exert their transcriptional effects. Sp1
      and Sp3 levels were found to be reduced in de-differentiated chondrocytes, as
      revealed by DNA-binding and immunochemical study. Sp1 specifically activated
      collagen neosynthesis whatever the differentiation state of chondrocytes,
      suggesting that this factor exerts a major role in the expression of collagen
      type II. However, our data indicate that type II collagen-specific expression in
      chondrocytes depend on both the Sp1/Sp3 ratio and cooperation of Sp1 with other
      transcription factors, the amounts of which are also modulated by phenotype
      alteration.

PMID- 11447233
TI  - The molecular chaperone, alpha-crystallin, inhibits amyloid formation by
      apolipoprotein C-II.
AB  - Under lipid-free conditions, human apolipoprotein C-II (apoC-II) exists in an
      unfolded conformation that over several days forms amyloid ribbons. We examined
      the influence of the molecular chaperone, alpha-crystallin, on amyloid formation
      by apoC-II. Time-dependent changes in apoC-II turbidity (at 0.3 mg/ml) were
      suppressed potently by substoichiometric subunit concentrations of alpha
      crystallin (1-10 microg/ml). alpha-Crystallin also inhibits time-dependent
      changes in the CD spectra, thioflavin T binding, and sedimentation coefficient of
      apoC-II. This contrasts with stoichiometric concentrations of alpha-crystallin
      required to suppress the amorphous aggregation of stressed proteins such as
      reduced alpha-lactalbumin. Two pieces of evidence suggest that alpha-crystallin
      directly interacts with amyloidogenic intermediates. First, sedimentation
      equilibrium and velocity experiments exclude high affinity interactions between
      alpha-crystallin and unstructured monomeric apoC-II. Second, the addition of
      alpha-crystallin does not lead to the accumulation of intermediate sized apoC-II
      species between monomer and large aggregates as indicated by gel filtration and
      sedimentation velocity experiments, suggesting that alpha-crystallin does not
      inhibit the relatively rapid fibril elongation upon nucleation. We propose that
      alpha-crystallin interacts stoichiometrically with partly structured
      amyloidogenic precursors, inhibiting amyloid formation at nucleation rather than
      the elongation phase. In doing so, alpha-crystallin forms transient complexes
      with apoC-II, in contrast to its chaperone behavior with stressed proteins.

PMID- 11447234
TI  - ESDN, a novel neuropilin-like membrane protein cloned from vascular cells with
      the longest secretory signal sequence among eukaryotes, is up-regulated after
      vascular injury.
AB  - A novel cDNA has been isolated from primary culture of human coronary arterial
      cells by a signal sequence trap method, and designated ESDN (endothelial and
      smooth muscle cell-derived neuropilin-like molecule). ESDN is a type-I
      transmembrane protein with the longest cleavable secretory signal sequence among
      eukaryotes. ESDN contains a CUB domain and a coagulation factor V/VIII homology
      domain, which reminds us of the structure of neuropilins. ESDN also harbors an
      LCCL domain, which is shared by Limulus factor C and Coch. Mouse and rat
      counterparts were also identified revealing >84% amino acid identity with human
      ESDN. The human ESDN gene was mapped between D3S1552 and D3S1271. Northern blot
      analysis showed that ESDN mRNA was expressed in various tissues; particularly
      highly expressed in cultured vascular smooth muscle cells. The ESDN expression
      was up-regulated in platelet-derived growth factor-BB-stimulated vascular smooth
      muscle cells in vitro and neointima of the balloon-injured carotid artery in
      vivo. Overexpression of ESDN in 293T cells suppressed their bromodeoxyuridine
      uptake. In addition, ESDN protein was strongly expressed in nerve bundles in
      rodents. Thus, ESDN is considered to play a role in regulation of vascular cell
      growth and may have a wide variety of functions in other tissues including the
      nervous system, like neuropilins.

PMID- 11447235
TI  - Metabolism of prostaglandin glycerol esters and prostaglandin ethanolamides in
      vitro and in vivo.
AB  - Prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs)
      are generated by the action of cyclooxygenase-2 on the endocannabinoids 2
      arachidonylglycerol (2-AG) and arachidonylethanolamide, respectively. These novel
      eicosanoids may have unique pharmacological properties and/or serve as latent
      sources of prostaglandins at sites remote from their tissue of origin. Therefore,
      we investigated the metabolism of PG-Gs and PG-EAs in vitro and in vivo. PGE(2)-G
      was rapidly hydrolyzed in rat plasma to generate PGE(2) (t(1/2) = 14 s) but was
      only slowly metabolized in human plasma (t(1/2) > 10 min). An intermediate extent
      of metabolism of PGE(2)-G was observed in human whole blood (t(1/2) approximately
      7 min). The parent arachidonylglycerol, 2-AG, and the more stable regioisomer, 1
      AG, also were much more rapidly metabolized in rat plasma compared with human
      plasma. PGE(2)-EA was not significantly hydrolyzed in plasma, undergoing slow
      dehydration/isomerization to PGB(2)-EA. Both PGE(2)-G and PGE(2)-EA were stable
      in canine, bovine, and human cerebrospinal fluid. Human 15-hydroxyprostaglandin
      dehydrogenase, the enzyme responsible for the initial step in PG inactivation in
      vivo, oxidized both PGE(2)-G and PGE(2)-EA less efficiently than the free acid.
      The sterically hindered glyceryl prostaglandin was the poorest substrate examined
      in the E series. Minimal 15-hydroxyprostaglandin dehydrogenase oxidation of PGF(2
      alpha)-G was observed. PGE(2)-G and PGE(2)-EA pharmacokinetics were assessed in
      rats. PGE(2)-G was not detected in plasma 5 min following an intravenous dose of
      2 mg/kg. However, PGE(2)-EA was detectable up to 2 h following an identical dose,
      displaying a large apparent volume of distribution and a half-life of over 6 min.
      The results suggest that endocannabinoid-derived PG-like compounds may be
      sufficiently stable in humans to exert actions systemically. Furthermore, these
      results suggest that the rat is not an adequate model for investigating the
      biological activities of 2-arachidonylglycerol or glyceryl prostaglandins in
      humans.

PMID- 11447236
TI  - Current status of the river buffalo (Bubalus bubalis L.) gene map.
AB  - Ninety-nine loci have been assigned to river buffalo chromosomes, 67 of which are
      coding genes and 32 of which are anonymous DNA segments (microsatellites). Sixty
      seven assignments were based on cosegregation of cellular markers in somatic cell
      hybrids (synteny), whereas 39 were based on in situ hybridization of fixed
      metaphase chromosomes with labeled DNA probes. Seven loci were assigned by both
      methods. Of the 67 assignments in somatic cell hybrids, 38 were based on
      polymerase chain reaction (PCR), 11 on isozyme electrophoresis, 10 on restriction
      endonuclease digestion of DNA, 4 on immunofluorescence, and 4 on chromosomal
      identification. A genetic marker or syntenic group has been assigned to each arm
      of the five submetacentric buffalo chromosomes as well as to the 19 acrocentric
      autosomes, and the X and Y chromosomes. These same markers map to the 29 cattle
      autosomes and the X and Y chromosomes, and without exception, cattle markers map
      to the buffalo chromosome or chromosomal region predicted from chromosome banding
      similarity.

PMID- 11447237
TI  - Subspecific affinity of black bears in the White River National Wildlife Refuge.
AB  - The black bear population of the White River National Wildlife Refuge (NWR) is
      adjacent to populations of black bear in Louisiana (Urusus americanus luteolus)
      which are listed as threatened under the U.S. Endangered Species Act. Wildlife
      management plans can pose restrictions on bear harvests and timber extraction;
      therefore the management plan for the White River NWR is sensitive to subspecific
      classification of its bear population. The objective of this study was to analyze
      genetic variation in the White River NWR and seven adjacent populations of black
      bears to assess the subspecific affinity of the White River NWR population. Here
      we report the variation at seven microsatellite DNA loci among eight black bear
      populations. The patterns of genetic variation gave strong support for
      distinguishing a southern group of black bears comprised of the White River,
      Arkansas; Tensas River, Louisiana; Upper Atchafalaya, Louisiana; Lower
      Atchafalaya, Louisiana; and Alabama/Mississippi populations. Phylogenetic
      analysis of individual variation suggested that historical black bear
      introductions into Arkansas and Louisiana affected gene pools of certain southern
      receiving populations, but did not significantly change interpopulation
      relatedness. Phylogenetic inferences at both the population and individual levels
      support the hypothesis that the White River NWR population of black bears belongs
      to the U. a. luteolus subspecies.

PMID- 11447238
TI  - Inheritance of a temperature-modified phenotype of the short antennae (sa)
      mutation in a moth, Ephestia kuehniella (Lepidoptera: Pyralidae).
AB  - The autosomal recessive mutation short antennae (sa) causes considerable
      shortening of antennae in male and female Mediterranean flour moths (Ephestia
      kuehniella Zeller). However, the sa phenotype can be suppressed by several
      physical factors, making sa moths indistinguishable from wild-type moths
      (sa(WT)). This can be done by subjecting larva and pupa to a higher temperature
      (25 degrees C), to lithium ions, or to an alternate electric field. The first
      half of pupal development was found to be the sensitive period for the sa(WT)
      phenotype. The sa(WT) phenotype is stable and cannot be reverted to the original
      sa type by physical or chemical factors. The sa(WT) phenotype is transmitted to
      future generations. When crossed with typical sa moths, the sa(WT) phenotype is
      inherited either as a dominant character if carried by males or a semidominant
      character if carried by females. We compared proteins of the ejaculate, accessory
      gland secretions, and spermatophore in sa, sa(WT), and wild-type males and found
      considerable differences between sperm proteins of sa(WT), sa, and wild-type
      males. The sa(WT) phenotype influences the mating success of males: sa(WT) males
      mated successfully with any females, whereas typical sa males were less
      successful in mating and then mainly with females of the same phenotype.

PMID- 11447239
TI  - The aunt and uncle effect: an empirical evaluation of the confounding influence
      of full sibs of parents on pedigree reconstruction.
AB  - This study used simulations and a known two-generation pedigree of chinook salmon
      (Oncorhynchus tshawytscha) to evaluate the effect of full sibs of parents on
      pedigree reconstruction. Parentage analysis was conducted on 100 parent pair
      offspring relationships from pedigrees with unrelated (simulation) and related
      (chinook salmon) candidate parents. Parentage assignment success for the chinook
      salmon was lower than in the simulated populations. For example, the six most
      variable loci (mean H(E) = 0.87) provided a mean of 97% unambiguous assignments
      in the simulated population and 67% unambiguous assignments for the chinook
      salmon. Estimates of the pairwise relatedness coefficient ((xy)) for most
      nonexcluded false parents and true parents of chinook salmon offspring exceeded
      0.50. These results support the conclusion that closely related candidate parents
      decrease the power of genetic markers for pedigree reconstruction based on
      exclusion. Ambiguous parentage may be resolved using single parent- and parent
      pair-offspring likelihood analysis, however, these methods should be used with
      caution and they are not replacements for using more loci when many candidate
      parents are full sibs.

PMID- 11447240
TI  - Widespread heteroplasmy in schistosomes makes an mtVNTR marker "nearsighted".
AB  - Mitochondrial markers are often hailed as the preferred DNA elements for analyses
      of population subdivision. To this end we have employed a mitochondrial repeat
      element to examine the population structure in Schistosoma mansoni (human blood
      flukes). Schistosome isolates were collected from each of 21 different patients
      representing seven different areas of a Brazilian village. These parasite
      isolates demonstrate substantial genetic polymorphism, with an average of 10
      genotypes infecting each patient, which is more readily detected because of high
      levels of heteroplasmy (i.e., 72.5% of the individual worms exhibit multiple
      versions of this repeat region with different numbers of repeats). Due to the
      high number of common haplotypes in the population, this repeat element from S.
      mansoni has a large proportion (47%) of its genetic variation described by
      differences among mitochondrial genomes within individual worms. However, when
      only rare haplotypes are considered, population structure can be detected. It
      seems that heteroplasmy in the schistosome population of Melquiades is both the
      source of plentiful genetic variation and a confounding factor in the analysis of
      that variation. Thus the schistosome population in Melquiades may actually be
      more strongly subdivided than we are able to detect using this mitochondrial
      marker.

PMID- 11447241
TI  - Production of near-isogenic lines and marked monosomic lines in common wheat
      (Triticum aestivum) cv. Chinese Spring.
AB  - Sixteen near-isogenic lines (NILs) carrying a marker gene were produced by the
      recurrent backcrossing method in the genetic background of common wheat (Triticum
      aestivum) cv. Chinese Spring (CS). Three genes from alien species showed
      segregation distortion. In NILs carrying a marker gene of rye (Secale cereale) or
      Aegilops caudata, the alien chromosome segments were detected by fluorescence in
      situ hybridization (FISH). The NILs were grown with replications and the effect
      of marker genes on plant morphology in the genetic background of CS was
      investigated. These NILs were further crossed with the corresponding monosomics
      of CS and 13 monosomic lines whose monosome carries a respective marker gene were
      established and named "marked monosomics." Many of the marked monosomics were
      distinguishable from the disomic NILs because of the different dosage effect of
      the genes. The NILs are utilized for studies on gene isolation or gene
      regulation. Marked monosomics are useful not only for monosomic analysis but also
      for production of homologous chromosome substitution lines because chromosome
      observation is not required.

PMID- 11447242
TI  - Evidence of variation in segregation patterns within a Cedrus population.
AB  - We used horizontal starch-gel electrophoresis for a genetic analysis of isozymes
      within one French Cedrus atlantica stand. Eleven to 29 megagametophytes per tree
      from 186 trees were assayed. Among the 33 enzyme systems tested, 15 correctly
      resolved and 8 appeared variable in at least one zone of activity: ACP, GOT, IDH,
      LAP, MDH, MNR, PGI, and SKDH. They were coded by at least 12 polymorphic loci
      which were described and tested for Mendelian segregation and linkage.
      Segregation patterns and linkage relationships were variable in the population.
      We detected homogeneous segregation distortion for loci Idh, Acp-c, and Got-a
      over the whole set of segregating progeny. We also found segregation distortions
      in a significant proportion of progeny for loci Got-b, Mdh-c, Pgi-b, and SKDH:
      The Acp-c and Got-b loci were linked with an overall map distance of 17 cM, but
      distance varied drastically among progeny. Both segregation distortions and
      heterogeneity of recombination frequencies indicate the occurrence of a genetic
      load in this population.

PMID- 11447243
TI  - Molecular mapping of Rxp conditioning reaction to bacterial pustule in soybean.
AB  - The Rxp locus in soybean [Glycine max (L.) Merr.] that conditions reaction to
      bacterial pustule was mapped by simple sequence repeat (SSR) marker analysis. A
      population of 116 F4-derived lines from a cross between the resistant parent
      Young and the susceptible parent PI 416937 was used for mapping. The Rxp locus
      was mapped 3.9 cM from Satt372 and 12.4 cM from Satt014 on linkage group D2.
      Linkage associations were confirmed by identifying a close association between
      the SSR genotype at each locus identified as flanking Rxp and the bacterial
      pustule reaction of individual lines derived from a population different from the
      one used for mapping. A molecular pedigree analysis showed that bacterial pustule
      resistant cultivars inherited the resistance gene rxp from the ancestral cultivar
      CNS based on their consistent genotypic pattern at flanking marker loci. Based on
      the results of the study, marker-assisted selection for rxp would be very
      effective.

PMID- 11447244
TI  - Inheritance and subcellular localization of triose-phosphate isomerase in dwarf
      mountain pine (Pinus mugo).
AB  - Several trees with expected heterozygous phenotype for triose-phosphate isomerase
      (TPI) were discovered in a population of dwarf mountain pine (Pinus mugo Turra)
      from southern Poland. As the inheritance of this enzyme in pines has not been
      reported, segregation of allelic variants was tested in eight trees with putative
      heterozygous phenotypes for two loci, TpiA and TPIB: Linkage between these and
      some other isozyme loci were studied and evidence for linkage has been found
      between TpiA and PgdA (r = 0.10) and between TpiB and DiaD (r = 0.36), but in
      single trees only. The subcellular localization of TPI isozymes was determined by
      comparing isoenzymes from the total extract with those found in fraction enriched
      in plastids, prepared by differential gradient centrifugation of cellular
      organelles. The more slowly migrating TPI-B isozyme is located in plastids.

PMID- 11447245
TI  - Extension of the Castle-Wright effective factor estimator to sex linkage and
      haplodiploidy.
AB  - The Castle-Wright effective factor estimator gives a minimum estimate of the
      number of genes underlying complex traits. Because the Castle-Wright estimator
      does not rely on genetic markers, it is especially useful in genetically
      undeveloped species. In this article I describe two extensions of this estimator.
      The first corrects the estimator in heterogametic (XY) species with a partially
      sex-linked trait. In this case the traditional estimator underestimates gene
      number in F2 males and overestimates it in F2 females and backcross females and
      males. The second extension adapts the Castle-Wright equation to haplodiploid
      species.

PMID- 11447246
TI  - Microsatellite polymorphism in closely related dogs.
AB  - The effectiveness of microsatellites in parentage testing and individual
      identification has been proven in many species, including dogs. However, the use
      of these markers has not been extended to control for pedigrees in large
      populations of closely related animals. We have analyzed polymorphism in a set of
      10 microsatellites over three generations of 360 pedigree rottweilers. Results
      were compared with two pure-bred populations of unrelated animals and with one
      population constituted by unrelated dogs of mixed breeds to measure polymorphism
      variation. We optimized this set of microsatellites to be analyzed by a
      semiautomated capillary electrophoresis method after amplification in two
      multiplex polymerase chain reactions (PCRs). The mean polymorphism information
      content (PIC) value in the rottweiler pedigree is 0.401 and the combined
      paternity exclusion probability (CPE) is 95.6%. These values are similar to those
      obtained in pure-bred populations of unrelated animals, and although polymorphism
      is reduced in relation to the pool population, we solved all paternity
      exclusions. In only a few cases did we have to use two additional microsatellites
      to solve individual identification of full-sib dogs.

PMID- 11447247
TI  - Inheritance pattern of RAPD markers in Melipona quadrifasciata (Hymenoptera:
      Apidae, Meliponinae).
AB  - Melipona quadrifasciata is an important pollinator agent in several regions of
      Brazil. Data concerning the genetics of this species are scarce in the
      literature. In this work we used the random amplified polymorphic DNA (RAPD)
      technique to determine the degree of polymorphism and the inheritance pattern of
      these molecular markers in this species. Our ultimate goal is to establish tools
      to be used in the study of the genomic organization of M. quadrifasciata. Genomic
      DNA from progenies F(1) and BC(1) were assayed with 79 different primers,
      yielding an average of 6.67 bands and 1.68 polymorphisms per primer. Three types
      of polymorphisms were detected: band presence/absence, band intensity, and
      fragment-length polymorphisms. Most of the observed polymorphisms were band
      presence/absence, typical of RAPD-dominant markers. The number of observed
      polymorphisms and their segregation in accordance with a Mendelian proportion
      confirm the importance of this technique for genome analysis of species like M.
      quadrifasciata that are poorly studied at the genetic level.

PMID- 11447248
TI  - Chromosomal mapping of 18S-28S rRNA genes and 10 cDNA clones of human chromosome
      1 in the musk shrew (Suncus murinus).
AB  - The direct R-banding fluorescence in situ hybridization (FISH) method was used to
      map 18S-28S ribosomal RNA genes and 10 human cDNA clones on the chromosomes of
      the musk shrew (Suncus murinus). The chromosomal locations of 18S-28S ribosomal
      RNA genes were examined in the five laboratory lines and wild animals captured in
      the Philippines and Vietnam, and the genes were found on chromosomes 5, 6, 9, and
      13 with geographic variation. The comparative mapping of 10 cDNA clones of human
      chromosome 1 demonstrated that human chromosome 1 consisted of at least three
      segments homologous to Suncus chromosomes (chromosomes 7, 10, and 14). This
      approach with the direct R-banding FISH method is useful for constructing
      comparative maps between human and insectivore species and for explicating the
      process of chromosomal rearrangements during the evolution of mammals.

PMID- 11447249
TI  - A cryptic RRY(i) microsatellite from Atlantic salmon (Salmo salar):
      characterization and chromosomal location.
AB  - In this article we describe the isolation and characterization of a cryptic
      RRY(i) microsatellite from an Atlantic salmon genomic cosmid library. The
      chromosomal location of the microsatellite-containing cosmid was performed by
      fluorescent in situ hybridization (FISH) showing a single-locus signal located on
      an interstitial position of an acrocentric pair. The suitability of this type of
      microsatellite marker for population genetic analysis and for the development of
      a genetic map in this species is discussed. In addition, the usefulness of cosmid
      libraries for physical mapping of microsatellite markers and therefore for the
      integration of physical and genetic maps is pointed out.

PMID- 11447250
TI  - A QTL study of cattle behavioral traits in embryo transfer families.
AB  - Two behavioral traits, temperament and habituation, were measured in 130 calves
      from 17 full-sib families which comprise the Canadian Beef Cattle Reference Herd.
      Using variance components, heritability was calculated as 0.36 for temperament
      and 0.46 for habituation. Genotyping of 162 microsatellites at approximately 20
      cM intervals allowed the detection of six quantitative trait loci (QTL) for
      behavior traits on cattle chromosomes 1, 5, 9, 11, 14, 15.

PMID- 11447251
TI  - SSR markers for Quercus suber tree identification and embryo analysis.
AB  - Three Quercus simple sequence repeat (SSR) markers were amplified by polymerase
      chain reaction (PCR) from nuclear DNA extracts of trees and in vitro-induced
      haploid embryos from anther cultures of Quercus suber L. These markers were
      sufficiently polymorphic to identify 10 of 12 trees located in two Spanish
      natural areas. The same loci have been analyzed in anther-derived haploid embryos
      showing the parental tree allele segregation. All the alleles were present in the
      haploid progeny. The presence of diverse alleles in embryos derived from the same
      anther demonstrated that they were induced on multiple microspores or pollen
      grains and they were not clonally propagated. Also, diploid cultures and mixtures
      of haploid-diploid tissues were obtained. The origin of such cultures, either
      somatic or gametic, was elucidated by SSR markers. All the embryos showed only
      one allele, corroborating a haploid origin. Allelic composition of the haploid
      progeny permitted parental identification among all analyzed trees.

PMID- 11447252
TI  - FISH mapping of the 5S and 18S-28S rDNA loci in different species of Glycine.
AB  - Wild germplasms are often the only significant sources of useful traits for
      crops, such as soybean, that have limited genetic variability. Before these
      germplasms can be effectively manipulated they must be characterized at the
      cytological and molecular levels. Modern soybean probably arose through an
      ancient allotetraploid event and subsequent diploidization of the genome.
      However, wild Glycine species have not been intensively investigated for this
      ancient polyploidy. In this article we determined the number of both the 5S and
      18S-28S rDNA sequences in various members of the genus Glycine using FISH. Our
      results distinctly establish the loss of a 5S rDNA locus from the "diploid" (2n =
      40) species and the loss of two from the (2n = 80) polyploids of GLYCINE: A
      similar diploidization of the 18S-28S rDNA gene family has occurred in G.
      canescens, G. clandestina, G. soja, and G. max (L.) Merr. (2n = 40). Although of
      different genome types, G. tabacina and G. tomentella (2n = 80) both showed two
      major 18S-28S rDNA loci per haploid genome, in contrast to the four loci that
      would be expected in chromosomes that have undergone two doubling events in their
      evolutionary history. It is evident that the evolution of the subgenus Glycine is
      more complex than that represented in a simple diploid-doubled to tetraploid
      model.

PMID- 11447253
TI  - EASYPOP (version 1.7): a computer program for population genetics simulations.

PMID- 11447254
TI  - A polymorphic dinucleotide repeat in the rat nucleolin gene forms Z-DNA and
      inhibits promoter activity.
AB  - Many sequences in eukaryotic genomes have the potential to adopt a left-handed Z
      DNA conformation. We used a previously described assay based on the binding of a
      mAb to Z-DNA to inquire whether Z-DNA is formed in the rat nucleolin (Ncl) gene
      in metabolically active, permeabilized nuclei. Using real-time PCR to measure Z
      DNA formation, the potential Z-DNA sequence element Z1 [(CA)(10)(CG)(8)] in the
      promoter region was found to be enriched 571- to 4,040-fold in different cell
      lines, whereas Z2 [AC(GC)(5)CCGT(CG)(2)] in the first intron was enriched 12- to
      34-fold. Ncl promoter activity was 1.5- to 16-fold stronger than that of the
      simian virus 40 promoter and enhancer. This activity was further increased 36-54%
      when Z1 was deleted. The inhibitory effect of Z1 on Ncl promoter activity was
      independent of location and orientation. The Ncl Z1 element is identical to the
      genetic marker D9Arb5. Five allelic variants of Z1 were identified by sequence
      analysis of genomic DNA from various rats. The two most common alleles differed
      significantly (up to 27%) in their capacity to inhibit Ncl promoter activity.
      This finding suggests that differences in Z-DNA formation by polymorphic
      dinucleotide repeats may be one of the factors contributing to genetic variation.

PMID- 11447255
TI  - Use of cDNA subtraction and RNA interference screens in combination reveals genes
      required for germ-line development in Caenorhabditis elegans.
AB  - Caenorhabditis elegans is an ideal organism for the study of the molecular basis
      of fundamental biological processes such as germ-line development, especially
      because of availability of the whole genome sequence and applicability of the RNA
      interference (RNAi) technique. To identify genes involved in germ-line
      development, we produced subtracted cDNA pools either enriched for or deprived of
      the cDNAs from germ-line tissues. We then performed differential hybridization on
      the high-density cDNA grid, on which about 7,600 nonoverlapping expressed
      sequence tag (EST) clones were spotted, to identify a set of genes specifically
      expressed in the germ line. One hundred and sixty-eight clones were then tested
      with the RNAi technique. Of these, 15 clones showed sterility with a variety of
      defects in germ-line development. Seven of them led to the production of
      unfertilized eggs, because of defects in spermatogenesis (4 clones), or defects
      in the oocytes (3 clones). The other 8 clones led to failure of oogenesis. These
      failures were caused by germ-line proliferation defect (Glp phenotype), meiotic
      arrest, and defects in sperm--oocyte switch (Mog phenotype) among others. These
      results demonstrate the efficacy of the screening strategy using the EST library
      combined with the RNAi technique in C. elegans.

PMID- 11447256
TI  - Mechanism of DNA polymerase II-mediated frameshift mutagenesis.
AB  - Escherichia coli possesses three SOS-inducible DNA polymerases (Pol II, IV, and
      V) that were recently found to participate in translesion synthesis and
      mutagenesis. Involvement of these polymerases appears to depend on the nature of
      the lesion and its local sequence context, as illustrated by the bypass of a
      single N-2-acetylaminofluorene adduct within the NarI mutation hot spot. Indeed,
      error-free bypass requires Pol V (umuDC), whereas mutagenic (-2 frameshift)
      bypass depends on Pol II (polB). In this paper, we show that purified DNA Pol II
      is able in vitro to generate the -2 frameshift bypass product observed in vivo at
      the NarI sites. Although the Delta polB strain is completely defective in this
      mutation pathway, introduction of the polB gene on a low copy number plasmid
      restores the -2 frameshift pathway. In fact, modification of the relative copy
      number of polB versus umuDC genes results in a corresponding modification in the
      use of the frameshift versus error-free translesion pathways, suggesting a direct
      competition between Pol II and V for the bypass of the same lesion. Whether such
      a polymerase competition model for translesion synthesis will prove to be
      generally applicable remains to be confirmed.

PMID- 11447257
TI  - How alpha beta T cells deal with induced TCR alpha ablation.
AB  - On deletion of the gene encoding the constant region of the T cell antigen
      receptor (TCR)alpha chain in mature T cells by induced Cre-mediated
      recombination, the cells lose most of their TCR from the cell surface within 7-
      10 days, but minute amounts of surface-bound TCR beta chains are retained for
      long periods of time. In a situation in which cellular influx from the thymus is
      blocked, TCR-deficient naive T cells decay over time, the decay rates being
      faster for CD8(+) cells (t(1/2) approximately 16 days) than for CD4(+) cells
      (t(1/2) approximately 46 days). TCR(+) naive cells are either maintained (CD8(+))
      or decay more slowly (CD4(+); t(1/2) approximately 78 days.) Numbers of TCR
      deficient memory T cells decline very slowly (CD8(+) cells; t(1/2) approximately
      52 days) or not at all (CD4(+) cells), but at the population level, these cells
      fail to expand as their TCR(+) counterparts do. Together with earlier data on T
      cell maintenance in environments lacking appropriate major histocompatibility
      complex antigens, these data argue against the possibility that spontaneous
      ligand-independent signaling by the alpha beta TCR contributes significantly to T
      cell homeostasis.

PMID- 11447258
TI  - The relaxation dynamics of the excited electronic states of retinal in
      bacteriorhodopsin by two-pump-probe femtosecond studies.
AB  - We present the results of two-pump and probe femtosecond experiments designed to
      follow the relaxation dynamics of the lowest excited state (S(1)) populated by
      different modes. In the first mode, a direct (S(0) --> S(1)) radiative excitation
      of the ground state is used. In the second mode, an indirect excitation is used
      where the S(1) state is populated by the use of two femtosecond laser pulses with
      different colors and delay times between them. The first pulse excites the S(0) -
      > S(1) transition whereas the second pulse excites the S(1) --> S(n) transition.
      The nonradiative relaxation from the S(n) state populates the lowest excited
      state. Our results suggest that the S(1) state relaxes faster when populated
      nonradiatively from the S(n) state than when pumped directly by the S(0) --> S(1)
      excitation. Additionally, the S(n) --> S(1) nonradiative relaxation time is found
      to change by varying the delay time between the two pump pulses. The observed
      dependence of the lowest excited state population as well as its dependence on
      the delay between the two pump pulses are found to fit a kinetic model in which
      the S(n) state populates a different surface (called S'(1)) than the one being
      directly excited (S(1)). The possible involvement of the A(g) type states, the J
      intermediate, and the conical intersection leading to the S(0) or to the
      isomerization product (K intermediate) are discussed in the framework of the
      proposed model.

PMID- 11447259
TI  - Tbx19, a tissue-selective regulator of POMC gene expression.
AB  - Pituitary cell types arise in a temporally and spatially specific fashion, in
      response to combinatorial actions of transcription factors induced by transient
      signaling gradients. The critical transcriptional determinants of the two
      pituitary cell types that express the pro-opiomelanocortin (POMC) gene, the
      anterior lobe corticotropes, producing adrenocorticotropin, and the intermediate
      lobe melanotropes, producing melanocyte-stimulating hormone (MSH alpha), have
      remained unknown. Here, we report that a member of the T-box gene family, Tbx19,
      which is expressed only in the rostral ventral diencephalon and pituitary gland,
      commencing on e11.5, marks pituitary cells that will subsequently express the
      POMC gene and is capable of altering progression of ventral cell types and
      inducing adrenocorticotropin in rostral tip cells. It is suggested that Tbx19,
      depending on the presence of synergizing transcription factors, can activate POMC
      gene expression and repress the alpha glycoprotein subunit and thyroid
      stimulating hormone beta promoters.

PMID- 11447260
TI  - Physical and functional interactions between Drosophila TRAF2 and Pelle kinase
      contribute to Dorsal activation.
AB  - Signaling through the Toll receptor is required for dorsal/ventral polarity in
      Drosophila embryos, and also plays an evolutionarily conserved role in the immune
      response. Upon ligand binding, Toll appears to multimerize and activate the
      associated kinase, Pelle. However, the immediate downstream targets of Pelle have
      not been identified. Here we show that Drosophila tumor necrosis factor receptor
      associated factor 2 (dTRAF2), a homologue of human TRAF6, physically and
      functionally interacts with Pelle, and is phosphorylated by Pelle in vitro.
      Importantly, dTRAF2 and Pelle cooperate to activate Dorsal synergistically in
      cotransfected Schneider cells. Deletion of the C-terminal TRAF domain of dTRAF2
      enhances Dorsal activation, perhaps reflecting the much stronger interaction of
      the mutant protein with phosphorylated, active Pelle. Taken together, our results
      indicate that Pelle and dTRAF2 physically and functionally interact, and that the
      TRAF domain acts as a regulator of this interaction. dTRAF2 thus appears to be a
      downstream target of Pelle. We discuss these results in the context of Toll
      signaling in flies and mammals.

PMID- 11447261
TI  - A two-hybrid system for transactivator bait proteins.
AB  - We describe a two-hybrid strategy for detection of interactions with
      transactivator proteins. This repressed transactivator (RTA) system employs the N
      terminal repression domain of the yeast general repressor TUP1. TUP1-GAL80 fusion
      proteins, when coexpressed with GAL4, are shown to inhibit transcription of GAL4
      dependent reporter genes. This effect requires the C-terminal 30 residues of
      GAL4, which are required for interaction with GAL80 in vitro. Furthermore,
      repression of GAL transcription by TUP1-GAL80 requires SRB10, demonstrating that
      the TUP1 repression domain, in the context of a two-hybrid interaction, functions
      by the same mechanism as endogenous TUP1. Using this strategy, we demonstrate
      interactions between the mammalian basic helix-loop-helix proteins MyoD and E12,
      and between c-Myc and Bin-1. We have also identified interacting clones from a
      TUP1-cDNA fusion expression library by using GAL4-VP16 as a bait fusion. These
      results demonstrate that RTA is generally applicable for identifying and
      characterizing interactions with transactivator proteins in vivo.

PMID- 11447262
TI  - Telomerase expression and activity are coupled with myocyte proliferation and
      preservation of telomeric length in the failing heart.
AB  - The role and even the existence of myocyte proliferation in the adult heart
      remain controversial. Documentation of cell cycle regulators, DNA synthesis, and
      mitotic images has not modified the view that myocardial growth can only occur
      from hypertrophy of an irreplaceable population of differentiated myocytes. To
      improve understanding the biology of the heart and obtain supportive evidence of
      myocyte replication, three indices of cell proliferation were analyzed in dogs
      affected by a progressive deterioration of cardiac performance and dilated
      cardiomyopathy. The magnitude of cycling myocytes was evaluated by the expression
      of Ki67 in nuclei. Ki67 labeling of left ventricular myocytes increased 5-fold,
      12-fold, and 17-fold with the onset of moderate and severe ventricular
      dysfunction and overt failure, respectively. Telomerase activity in vivo is
      present only in multiplying cells; this enzyme increased 2.4-fold and 3.1-fold in
      the decompensated heart, preserving telomeric length in myocytes. The
      contribution of cycling myocytes to telomerase activity was determined by the
      colocalization of Ki67 and telomerase in myocyte nuclei. More than 50% of Ki67
      positive cells expressed telomerase in the overloaded myocardium, suggesting that
      these myocytes were the morphological counterpart of the biochemical assay of
      enzyme activity. Moreover, we report that 20--30% of canine myocytes were
      telomerase competent, and this value was not changed by cardiac failure. In
      conclusion, the enhanced expression of Ki67 and telomerase activity, in
      combination with Ki67-telomerase labeling of myocyte nuclei, support the notion
      that myocyte proliferation contributes to cardiac hypertrophy of the diseased
      heart.

PMID- 11447263
TI  - A role for CD36 in the regulation of dendritic cell function.
AB  - Dendritic cells (DC) are crucial for the induction of immune responses and thus
      an inviting target for modulation by pathogens. We have previously shown that
      Plasmodium falciparum-infected erythrocytes inhibit the maturation of DCs. Intact
      P. falciparum-infected erythrocytes can bind directly to CD36 and indirectly to
      CD51. It is striking that these receptors, at least in part, also mediate the
      phagocytosis of apoptotic cells. Here we show that antibodies against CD36 or
      CD51, as well as exposure to early apoptotic cells, profoundly modulate DC
      maturation and function in response to inflammatory signals. Although modulated
      DCs still secrete tumor necrosis factor-alpha, they fail to activate T cells and
      now secrete IL-10. We therefore propose that intact P. falciparum-infected
      erythrocytes and apoptotic cells engage similar pathways regulating DC function.
      These findings may have important consequences for the treatment of malaria and
      may suggest strategies for modulating pathological immune responses in autoimmune
      diseases.

PMID- 11447264
TI  - Nanoparticle halos: a new colloid stabilization mechanism.
AB  - A new mechanism for regulating the stability of colloidal particles has been
      discovered. Negligibly charged colloidal microspheres, which flocculate when
      suspended alone in aqueous solution, undergo a remarkable stabilizing transition
      upon the addition of a critical volume fraction of highly charged nanoparticle
      species. Zeta potential analysis revealed that these microspheres exhibited an
      effective charge buildup in the presence of such species. Scanning angle
      reflectometry measurements indicated, however, that these nanoparticle species
      did not adsorb on the microspheres under the experimental conditions of interest.
      It is therefore proposed that highly charged nanoparticles segregate to regions
      near negligibly charged microspheres because of their repulsive Coulombic
      interactions in solution. This type of nanoparticle haloing provides a previously
      unreported method for tailoring the behavior of complex fluids.

PMID- 11447265
TI  - Sexually antagonistic coevolution of a postmating-prezygotic reproductive
      character in desert Drosophila.
AB  - Rapid divergence in postmating-prezygotic characters suggests that selection may
      be responsible for generating reproductive barriers between closely related
      species. Theoretical models indicate that this rapid divergence could be
      generated by a series of male adaptations and female counteradaptations by means
      of sexual selection or conflict, but empirical tests of particular mechanisms are
      generally lacking. Moreover, although a male--female genotypic interaction in
      mediating sperm competition attests to an active role of females, molecular or
      morphological evidence of the female's participation in the coevolutionary
      process is critically needed. Here we show that postmating-prezygotic variation
      among populations of cactophilic desert Drosophila reflects divergent
      coevolutionary trajectories between the sexes. We explicitly test the female's
      role in intersexual interactions by quantifying differences in a specific
      postmating-prezygotic reproductive character, the insemination reaction mass, in
      two species, Drosophila mojavensis and Drosophila arizonae. A series of
      interpopulation crosses confirmed that population divergence was propelled by
      male--female interactions, a prerequisite if the selective forces derive from
      sexual conflicts. An association between the reaction mass and remating and
      oviposition behavior argues that divergence has been propelled by sexually
      antagonistic coevolution, and potentially has important implications for
      speciation.

PMID- 11447266
TI  - NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers
      NO to the liver and protects against development of portal hypertension.
AB  - Portal hypertension resulting from increased intrahepatic resistance is a common
      complication of chronic liver diseases and a leading cause of death in patients
      with liver cirrhosis, a scarring process of the liver that includes components of
      both increased fibrogenesis and wound contraction. A reduced production of nitric
      oxide (NO) resulting from an impaired enzymatic function of endothelial NO
      synthase and an increased contraction of hepatic stellate cells (HSCs) have been
      demonstrated to contribute to high intrahepatic resistance in the cirrhotic
      liver. 2-(Acetyloxy) benzoic acid 3-(nitrooxymethyl) phenyl ester (NCX-1000) is a
      chemical entity obtained by adding an NO-releasing moiety to ursodeoxycholic acid
      (UDCA), a compound that is selectively metabolized by hepatocytes. In this study
      we have examined the effect of NCX-1000 and UDCA on liver fibrosis and portal
      hypertension induced by i.p. injection of carbon tetrachloride in rats. Our
      results demonstrated that although both treatments reduced liver collagen
      deposition, NCX-1000, but not UDCA, prevented ascite formation and reduced
      intrahepatic resistance in carbon tetrachloride-treated rats as measured by
      assessing portal perfusion pressure. In contrast to UDCA, NCX-1000 inhibited HSC
      contraction and exerted a relaxing effect similar to the NO donor S-nitroso-N
      acetylpenicillamine. HSCs were able to metabolize NCX-1000 and release
      nitrite/nitrate in cell supernatants. In aggregate these data indicate that NCX
      1000, releasing NO into the liver microcirculation, may provide a novel therapy
      for the treatment of patients with portal hypertension.

PMID- 11447267
TI  - Lack of hepcidin gene expression and severe tissue iron overload in upstream
      stimulatory factor 2 (USF2) knockout mice.
AB  - We previously reported the disruption of the murine gene encoding the
      transcription factor USF2 and its consequences on glucose-dependent gene
      regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice
      that progressively develop multivisceral iron overload; plasma iron overcomes
      transferrin binding capacity, and nontransferrin-bound iron accumulates in
      various tissues including pancreas and heart. In contrast, the splenic iron
      content is strikingly lower in knockout animals than in controls. To identify
      genes that may account for the abnormalities of iron homeostasis in Usf2(-/-)
      mice, we used suppressive subtractive hybridization between livers from Usf2(-/-)
      and wild-type mice. We isolated a cDNA encoding a peptide, hepcidin (also
      referred to as LEAP-1, for liver-expressed antimicrobial peptide), that was very
      recently purified from human blood ultrafiltrate and from urine as a disulfide
      bonded peptide exhibiting antimicrobial activity. Accumulation of iron in the
      liver has been recently reported to up-regulate hepcidin expression, whereas our
      data clearly show that a complete defect in hepcidin expression is responsible
      for progressive tissue iron overload. The striking similarity of the alterations
      in iron metabolism between HFE knockout mice, a murine model of hereditary
      hemochromatosis, and the Usf2(-/-) hepcidin-deficient mice suggests that hepcidin
      may function in the same regulatory pathway as HFE. We propose that hepcidin acts
      as a signaling molecule that is required in conjunction with HFE to regulate both
      intestinal iron absorption and iron storage in macrophages.

PMID- 11447268
TI  - Prostaglandins are required for CREB activation and cellular proliferation during
      liver regeneration.
AB  - The liver responds to multiple types of injury with an extraordinarily well
      orchestrated and tightly regulated form of regeneration. The response to partial
      hepatectomy has been used as a model system to elucidate the molecular basis of
      this regenerative response. In this study, we used cyclooxygenase (COX)-selective
      antagonists and -null mice to determine the role of prostaglandin signaling in
      the response of liver to partial hepatectomy. The results show that liver
      regeneration is markedly impaired when both COX-1 and COX-2 are inhibited by
      indocin or by a combination of the COX-1 selective antagonist, SC-560, and the
      COX-2 selective antagonist, SC-236. Inhibition of COX-2 alone partially inhibits
      regeneration whereas inhibition of COX-1 alone tends to delay regeneration.
      Neither the rise in IL-6 nor the activation of signal transducer and activator of
      transcription-3 (STAT3) that is seen during liver regeneration is inhibited by
      indocin or the selective COX antagonists. In contrast, indocin treatment prevents
      the activation of CREB by phosphorylation that occurs during hepatic
      regeneration. These data indicate that prostaglandin signaling is required during
      liver regeneration, that COX-2 plays a particularly important role but COX-1 is
      also involved, and implicate the activation of CREB rather than STAT3 as the
      mediator of prostaglandin signaling during liver regeneration.

PMID- 11447269
TI  - Long-term, progressive hippocampal cell loss and dysfunction induced by early
      life administration of corticotropin-releasing hormone reproduce the effects of
      early-life stress.
AB  - Stress early in postnatal life may result in long-term memory deficits and
      selective loss of hippocampal neurons. The mechanisms involved are poorly
      understood, but they may involve molecules and processes in the immature limbic
      system that are activated by stressful challenges. We report that administration
      of corticotropin-releasing hormone (CRH), the key limbic stress modulator, to the
      brains of immature rats reproduced the consequences of early-life stress,
      reducing memory functions throughout life. These deficits were associated with
      progressive loss of hippocampal CA3 neurons and chronic up-regulation of
      hippocampal CRH expression. Importantly, they did not require the presence of
      stress levels of glucocorticoids. These findings indicate a critical role for CRH
      in the mechanisms underlying the long-term effects of early-life stress on
      hippocampal integrity and function.

PMID- 11447270
TI  - Dominant loss of responsiveness to sweet and bitter compounds caused by a single
      mutation in alpha -gustducin.
AB  - Biochemical and genetic studies have implicated alpha-gustducin as a key
      component in the transduction of both bitter or sweet taste. Yet, alpha-gustducin
      null mice are not completely unresponsive to bitter or sweet compounds. To gain
      insights into how gustducin mediates responses to bitter and sweet compounds, and
      to elicit the nature of the gustducin-independent pathways, we generated a
      dominant-negative form of alpha-gustducin and expressed it as a transgene from
      the alpha-gustducin promoter in both wild-type and alpha-gustducin-null mice. A
      single mutation, G352P, introduced into the C-terminal region of alpha-gustducin
      critical for receptor interaction rendered the mutant protein unresponsive to
      activation by taste receptor, but left its other functions intact. In control
      experiments, expression of wild-type alpha-gustducin as a transgene in alpha
      gustducin-null mice fully restored responsiveness to bitter and sweet compounds,
      formally proving that the targeted deletion of the alpha-gustducin gene caused
      the taste deficits of the null mice. In contrast, transgenic expression of the
      G352P mutant did not restore responsiveness of the null mice to either bitter or
      sweet compounds. Furthermore, in the wild-type background, the mutant transgene
      inhibited endogenous alpha-gustducin's interactions with taste receptors, i.e.,
      it acted as a dominant-negative. That the mutant transgene further diminished the
      residual bitter and sweet taste responsiveness of the alpha-gustducin-null mice
      suggests that other guanine nucleotide-binding regulatory proteins expressed in
      the alpha-gustducin lineage of taste cells mediate these responses.

PMID- 11447271
TI  - Histone deacetylase-dependent transcriptional repression by pRB in yeast occurs
      independently of interaction through the LXCXE binding cleft.
AB  - We have developed a yeast model system to address transcriptional repression by
      the retinoblastoma protein (pRB). When fused to the DNA-binding domain of Gal4p
      (DB-pRB), pRB can repress transcription of reporter genes containing Gal4p
      binding sites; the histone deacetylase activity encoded by yeast RPD3 is required
      for DB-pRB repression. Mutation of the LXCXE binding cleft in pRB, a region
      reported to be required for histone deacetylase recruitment, does not interfere
      with pRB-mediated repression. From these findings based on yeast experiments, we
      surmise that the small pocket region of pRB must contain an additional domain
      that confers histone deacetylase-dependent transcriptional repression. This
      hypothesis was verified by experiments examining pRB-dependent histone
      deacetylase association in mammalian cells. In addition to RPD3, repression by
      pRB in yeast requires MSI1, an ortholog of RbAp48, but not SIN3 or SAP30. By
      comparing the genetic requirements of DB-pRB repression in yeast to those of
      other DB-repressor fusions, we can suggest a mechanism by which pRB recruits
      histone deacetylase activity.

PMID- 11447272
TI  - Multiple vesiculoviral matrix proteins inhibit both nuclear export and import.
AB  - The matrix (M) protein of vesicular stomatitis virus inhibits both nuclear import
      and export. Here, we demonstrate that this inhibitory property is conserved
      between the M proteins from two other vesiculoviruses, chandipura virus and
      spring viremia carp virus. All three M proteins completely block nuclear
      transport of spliced mRNA, small nuclear RNAs, and small nuclear
      ribonucleoproteins and slow the nuclear transport of many other cargoes. In all
      cases where transport was merely slowed by the M proteins, the chandipura virus M
      protein had the strongest inhibitory activity. When expressed in transfected HeLa
      cells, active M proteins displayed prominent association with the nuclear rim.
      Moreover, mutation of a conserved methionine abolished both the inhibitory
      activity and efficient targeting of the M proteins to the nuclear rim. We propose
      that all of the vesiculoviral M proteins associate with the same nuclear target,
      which is likely to be a component of the nuclear pore complex.

PMID- 11447273
TI  - 4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma.
AB  - The estrogen-related receptors (ERR alpha, ERR beta, and ERR gamma) form a family
      of orphan nuclear receptors that share significant amino acid identity with the
      estrogen receptors, but for which physiologic roles remain largely unknown. By
      using a peptide sensor assay, we have identified the stilbenes diethylstilbestrol
      (DES), tamoxifen (TAM), and 4-hydroxytamoxifen (4-OHT) as high-affinity ligands
      for ERR gamma. In direct binding assays, 4-OHT had a K(d) value of 35 nM, and
      both DES and TAM displaced radiolabeled 4-OHT with K(i) values of 870 nM. In cell
      based assays, 4-OHT binding caused a dissociation of the complex between ERR
      gamma and the steroid receptor coactivator-1, and led to an inhibition of the
      constitutive transcriptional activity of ERR gamma. ERR alpha did not bind 4-OHT,
      but replacing a single amino acid predicted to be in the ERR alpha ligand-binding
      pocket with the corresponding ERR gamma residue allowed high-affinity 4-OHT
      binding. These results demonstrate the existence of high-affinity ligands for the
      ERR family of orphan receptors, and identify 4-OHT as a molecule that can
      regulate the transcriptional activity of ERR gamma.

PMID- 11447274
TI  - Molecular cloning and sequence analysis of the complestatin biosynthetic gene
      cluster.
AB  - Streptomyces lavendulae produces complestatin, a cyclic peptide natural product
      that antagonizes pharmacologically relevant protein-protein interactions
      including formation of the C4b,2b complex in the complement cascade and gp120-CD4
      binding in the HIV life cycle. Complestatin, a member of the vancomycin group of
      natural products, consists of an alpha-ketoacyl hexapeptide backbone modified by
      oxidative phenolic couplings and halogenations. The entire complestatin
      biosynthetic and regulatory gene cluster spanning ca. 50 kb was cloned and
      sequenced. It consisted of 16 ORFs, encoding proteins homologous to nonribosomal
      peptide synthetases, cytochrome P450-related oxidases, ferredoxins, nonheme
      halogenases, four enzymes involved in 4-hydroxyphenylglycine (Hpg) biosynthesis,
      transcriptional regulators, and ABC transporters. The nonribosomal peptide
      synthetase consisted of a priming module, six extending modules, and a terminal
      thioesterase; their arrangement and domain content was entirely consistent with
      functions required for the biosynthesis of a heptapeptide or alpha-ketoacyl
      hexapeptide backbone. Two oxidase genes were proposed to be responsible for the
      construction of the unique aryl-ether-aryl-aryl linkage on the linear
      heptapeptide intermediate. Hpg, 3,5-dichloro-Hpg, and 3,5-dichloro
      hydroxybenzoylformate are unusual building blocks that repesent five of the seven
      requisite monomers in the complestatin peptide. Heterologous expression and
      biochemical analysis of 4-hydroxyphenylglycine transaminon confirmed its role as
      an aminotransferase responsible for formation of all three precursors. The close
      similarity but functional divergence between complestatin and chloroeremomycin
      biosynthetic genes also presents a unique opportunity for the construction of
      hybrid vancomycin-type antibiotics.

PMID- 11447275
TI  - Contact interactions between epitheliocytes and fibroblasts: formation of
      heterotypic cadherin-containing adhesion sites is accompanied by local
      cytoskeletal reorganization.
AB  - Contact interactions between different cell types play a number of important
      roles in development, for example in cell sorting, tissue organization, and
      ordered migration of cells. The nature of such heterocellular interactions, in
      contrast to interactions between cells of the same type, remains largely unknown.
      In this report, we present experimental data examining the dynamics of
      heterocellular interactions between epitheliocytes and fibroblasts, which express
      different cadherin cell adhesion molecules and possess different actin
      cytoskeletal organizations. Our analysis revealed two striking features of
      heterocellular contact. First, the active free edge of an epitheliocyte
      reorganizes its actin cytoskeleton after making contact with a fibroblast. Upon
      contact with the leading edge of a fibroblast, epitheliocytes disassemble their
      marginal bundle of actin filaments and reassemble actin filaments into a
      geometric organization more typical of a fibroblast lamella. Second,
      epitheliocytes and fibroblasts form cell--cell adhesion structures that have an
      irregular organization and are associated with components of cell adhesion
      complexes. The structural organization of these adhesions is more closely related
      to the type of contacts formed between fibroblasts rather than to those between
      epitheliocytes. Heterotypic epithelio-fibroblastic contacts, like homotypic
      contacts between fibroblasts, are transient and do not lead to formation of
      stable contact interactions. We suggest that heterocellular contact interactions
      in culture may be regarded as models of how tissue systems consisting of
      epithelia and mesenchyme interact and become organized in vivo.

PMID- 11447276
TI  - Deficiency of human BRCA2 leads to impaired homologous recombination but
      maintains normal nonhomologous end joining.
AB  - Carriers of BRCA2 germline mutations are at high risk to develop early-onset
      breast cancer. The underlying mechanisms of how BRCA2 inactivation predisposes to
      malignant transformation have not been established. Here, we provide direct
      functional evidence that human BRCA2 promotes homologous recombination (HR),
      which comprises one major pathway of DNA double-strand break repair. We found
      that up-regulated HR after transfection of wild-type (wt) BRCA2 into a human
      tumor line with mutant BRCA2 was linked to increased radioresistance. In
      addition, BRCA2-mediated enhancement of HR depended on the interaction with
      Rad51. In contrast to the tumor suppressor BRCA1, which is involved in multiple
      DNA repair pathways, BRCA2 status had no impact on the other principal double
      strand break repair pathway, nonhomologous end joining. Thus, there exists a
      specific regulation of HR by BRCA2, which may function to maintain genomic
      integrity and suppress tumor development in proliferating cells.

PMID- 11447277
TI  - Apolipoprotein E fragments present in Alzheimer's disease brains induce
      neurofibrillary tangle-like intracellular inclusions in neurons.
AB  - Human apolipoprotein (apo) E4, a major risk factor for Alzheimer's disease (AD),
      occurs in amyloid plaques and neurofibrillary tangles (NFTs) in AD brains;
      however, its role in the pathogenesis of these lesions is unclear. Here we
      demonstrate that carboxyl-terminal-truncated forms of apoE, which occur in AD
      brains and cultured neurons, induce intracellular NFT-like inclusions in neurons.
      These cytosolic inclusions were composed of phosphorylated tau, phosphorylated
      neurofilaments of high molecular weight, and truncated apoE. Truncated apoE4,
      especially apoE4(Delta 272--299), induced inclusions in up to 75% of transfected
      neuronal cells, but not in transfected nonneuronal cells. ApoE4 was more
      susceptible to truncation than apoE3 and resulted in much greater intracellular
      inclusion formation. These results suggest that apoE4 preferentially undergoes
      intracellular processing, creating a bioactive fragment that interacts with
      cytoskeletal components and induces NFT-like inclusions containing phosphorylated
      tau and phosphorylated neurofilaments of high molecular weight in neurons.

PMID- 11447278
TI  - The trimer-of-hairpins motif in membrane fusion: Visna virus.
AB  - Structural studies of viral membrane fusion proteins suggest that a "trimer-of
      hairpins" motif plays a critical role in the membrane fusion process of many
      enveloped viruses. In this motif, a coiled coil (formed by homotrimeric
      association of the N-terminal regions of the protein) is surrounded by three C
      terminal regions that pack against the coiled coil in an oblique antiparallel
      manner. The resulting trimer-of-hairpins structure serves to bring the viral and
      cellular membranes together for fusion. learncoil-vmf, a computational program
      developed to recognize coiled coil-like regions that form the trimer-of-hairpins
      motif, predicts these regions in the membrane fusion protein of the Visna virus.
      Peptides corresponding to the computationally identified sequences were
      synthesized, and the soluble core of the Visna membrane fusion protein was
      reconstituted in solution. Its crystal structure at 1.5-A resolution demonstrates
      that a trimer-of-hairpins structure is formed. Remarkably, despite less than 23%
      sequence identity, the ectodomains in Visna and HIV-1 envelope glycoproteins show
      detailed structural conservation, especially within the area of a hydrophobic
      pocket in the central coiled coil currently being targeted for the development of
      new anti-HIV drugs.

PMID- 11447279
TI  - Force and kinetic barriers to unzipping of the DNA double helix.
AB  - A theory of the unzipping of double-stranded DNA is presented and is compared to
      recent micromanipulation experiments. It is shown that the interactions that
      stabilize the double helix and the elastic rigidity of single strands simply
      determine the sequence-dependent approximately 12-pN force threshold for DNA
      strand separation. Using a semimicroscopic model of the binding between
      nucleotide strands, we show that the greater rigidity of the strands when formed
      into double-stranded DNA, relative to that of isolated strands, gives rise to a
      potential barrier to unzipping. The effects of this barrier are derived
      analytically. The force to keep the extremities of the molecule at a fixed
      distance, the kinetic rates for strand unpairing at fixed applied force, and the
      rupture force as a function of loading rate are calculated. The dependence of the
      kinetics and of the rupture force on molecule length is also analyzed.

PMID- 11447280
TI  - Rescue of a Wnt mutation by an activated form of LEF-1: regulation of maintenance
      but not initiation of Brachyury expression.
AB  - Members of the LEF-1/TCF family of transcription factors have been implicated in
      mediating a nuclear response to Wnt signals by association with beta-catenin.
      Consistent with this view, mice carrying mutations in either the Wnt3a gene or in
      both transcription factor genes Lef1 and Tcf1 were previously found to show a
      similar defect in the formation of paraxial mesoderm in the gastrulating mouse
      embryo. In addition, mutations in the Brachyury gene, a direct transcriptional
      target of LEF-1, were shown to result in mesodermal defects. However, direct
      evidence for the role of LEF-1 and Brachyury in Wnt3a signaling has been
      limiting. In this study, we genetically examine the function of LEF-1 in the
      regulation of Brachyury expression and in signaling by Wnt3a. Analysis of the
      expression of Brachyury in Lef1(-/-)Tcf1(-/-) mice and studies of Brachyury:lacZ
      transgenes containing wild type or mutated LEF-1 binding sites indicate that Lef1
      is dispensable for the initiation, but is required for the maintenance of
      Brachyury expression. We also show that the expression of an activated form of
      LEF-1, containing the beta-catenin activation domain fused to the amino terminus
      of LEF-1, can rescue a Wnt3a mutation. Together, these data provide genetic
      evidence that Lef1 mediates the Wnt3a signal and regulates the stable maintenance
      of Brachyury expression during gastrulation.

PMID- 11447281
TI  - Sir3-dependent assembly of supramolecular chromatin structures in vitro.
AB  - Baculovirus-expressed recombinant Sir3p (rSir3p) has been purified to near
      homogeneity, and its binding to naked DNA, mononucleosomes, and nucleosomal
      arrays has been characterized in vitro. At stoichiometric levels rSir3p interacts
      with intact nucleosomal arrays, mononucleosomes, and naked DNA, as evidenced by
      formation of supershifted species on native agarose gels. Proteolytic removal of
      the core histone tail domains inhibits but does not completely abolish rSir3p
      binding to nucleosomal arrays. The linker DNA in the supershifted complexes
      remains freely accessible to restriction endonuclease digestion, suggesting that
      both the tail domains and nucleosomal DNA contribute to rSir3p--chromatin
      interactions. Together these data indicate that rSir3p cross-links individual
      nucleosomal arrays into supramolecular assemblies whose physical properties
      transcend those of typical 10-nm and 30-nm fibers. Based on these data we
      hypothesize that Sir3p functions, at least in part, by mediating reorganization
      of the canonical chromatin fiber into functionally specialized higher order
      chromosomal domains.

PMID- 11447282
TI  - Antibodies with infinite affinity.
AB  - Here we report an approach to the design and production of antibody/ligand pairs,
      to achieve functional affinity far greater than avidin/biotin. Using fundamental
      chemical principles, we have developed antibody/ligand pairs that retain the
      binding specificity of the antibody, but do not dissociate. Choosing a
      structurally characterized antibody/ligand pair as an example, we engineered
      complementary reactive groups in the antibody binding pocket and the ligand, so
      that they would be in close proximity in the antibody/ligand complex. Cross
      reactions with other molecules in the medium are averted because of the low
      reactivity of these groups; however, in the antibody/ligand complex the effective
      local concentrations of the complementary reactive groups are very large,
      allowing a covalent reaction to link the two together. By eliminating the
      dissociation of the ligand from the antibody, we have made the affinity
      functionally infinite. This chemical manipulation of affinity is applicable to
      other biological binding pairs.

PMID- 11447283
TI  - Somatic mosaicism in Wiskott--Aldrich syndrome suggests in vivo reversion by a
      DNA slippage mechanism.
AB  - Somatic mosaicism caused by in vivo reversion of inherited mutations has been
      described in several human genetic disorders. Back mutations resulting in
      restoration of wild-type sequences and second-site mutations leading to
      compensatory changes have been shown in mosaic individuals. In most cases,
      however, the precise genetic mechanisms underlying the reversion events have
      remained unclear, except for the few instances where crossing over or gene
      conversion have been demonstrated. Here, we report a patient affected with
      Wiskott--Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS
      protein gene, which abrogates protein expression. Somatic mosaicism was
      documented in this patient whose majority of T lymphocytes expressed nearly
      normal levels of WAS protein. These lymphocytes were found to lack the
      deleterious mutation and showed a selective growth advantage in vivo. Analysis of
      the sequence surrounding the mutation site showed that the 6-bp insertion
      followed a tandem repeat of the same six nucleotides. These findings strongly
      suggest that DNA polymerase slippage was the cause of the original germ-line
      insertion mutation in this family and that the same mechanism was responsible for
      its deletion in one of the propositus T cell progenitors, thus leading to
      reversion mosaicism.

PMID- 11447284
TI  - Tuning DNA "strings": modulating the rate of DNA replication with mechanical
      tension.
AB  - Recent experiments have measured the rate of replication of DNA catalyzed by a
      single enzyme moving along a stretched template strand. The dependence on tension
      was interpreted as evidence that T7 and related DNA polymerases convert two (n =
      2) or more single-stranded template bases to double helix geometry in the
      polymerization site during each catalytic cycle. However, we find structural data
      on the T7 enzyme--template complex indicate n = 1. We also present a model for
      the "tuning" of replication rate by mechanical tension. This model considers only
      local interactions in the neighborhood of the enzyme, unlike previous models that
      use stretching curves for the entire polymer chain. Our results, with n = 1,
      reconcile force-dependent replication rate studies with structural data on DNA
      polymerase complexes.

PMID- 11447285
TI  - Rolling-circle transposons in eukaryotes.
AB  - All eukaryotic DNA transposons reported so far belong to a single category of
      elements transposed by the so-called "cut-and-paste" mechanism. Here, we report a
      previously unknown category of eukaryotic DNA transposons, Helitron, which
      transpose by rolling-circle replication. Autonomous Helitrons encode a 5'-to-3'
      DNA helicase and nuclease/ligase similar to those encoded by known rolling-circle
      replicons. Helitron-like transposons have conservative 5'-TC and CTRR-3' termini
      and do not have terminal inverted repeats. They contain 16- to 20-bp hairpins
      separated by 10--12 nucleotides from the 3'-end and transpose precisely between
      the 5'-A and T-3', with no modifications of the AT target sites. Together with
      their multiple diverged nonautonomous descendants, Helitrons constitute
      approximately 2% of both the Arabidopsis thaliana and Caenorhabditis elegans
      genomes and also colonize the Oriza sativa genome. Sequence conservation suggests
      that Helitrons continue to be transposed.

PMID- 11447286
TI  - The endopolyphosphatase gene: essential in Saccharomyces cerevisiae.
AB  - Endopolyphosphatases (Ppn1) from yeast and animal cells hydrolyze inorganic
      polyphosphate (poly P) chains of many hundreds of phosphate residues into shorter
      lengths. The limit digest consists predominantly of chains of 60 (P(60)) and 3
      (P(3)) P(i) residues. Ppn1 of Saccharomyces cerevisiae, a homodimer of 35-kDa
      subunits (about 352-aa) is of vacuolar origin and requires the protease
      activation of a 75-kDa (674-aa) precursor polypeptide. The Ppn1 gene (PPN1) now
      has been cloned, sequenced, overexpressed, and deleted. That PPN1 encodes Ppn1
      was verified by a 25-fold increase in Ppn1 when overexpressed under a GAL
      promoter and also by several peptide sequences that match exactly with sequences
      in a yeast genome ORF, the mutation of which abolishes Ppn1 activity. Null
      mutants in Ppn1 accumulate long-chain poly P and are defective in growth in
      minimal media. A double mutant of PPN1 and PPX1 (the gene encoding a potent
      exopolyphosphatase) loses viability rapidly in stationary phase. Whether this
      loss is a result of the excess of long-chain poly P or to the lack of shorter
      chains (i.e., poly P(60) and P(3)) is unknown. Overexpression of the processed
      form of Ppn1 should provide a unique and powerful reagent to analyze poly P when
      the chain termini are unavailable to the actions of polyPase and poly P kinase.

PMID- 11447287
TI  - Evolutionary genomics of Staphylococcus aureus: insights into the origin of
      methicillin-resistant strains and the toxic shock syndrome epidemic.
AB  - An emerging theme in medical microbiology is that extensive variation exists in
      gene content among strains of many pathogenic bacterial species. However, this
      topic has not been investigated on a genome scale with strains recovered from
      patients with well-defined clinical conditions. Staphylococcus aureus is a major
      human pathogen and also causes economically important infections in cows and
      sheep. A DNA microarray representing >90% of the S. aureus genome was used to
      characterize genomic diversity, evolutionary relationships, and virulence gene
      distribution among 36 strains of divergent clonal lineages, including methicillin
      resistant strains and organisms causing toxic shock syndrome. Genetic variation
      in S. aureus is very extensive, with approximately 22% of the genome comprised of
      dispensable genetic material. Eighteen large regions of difference were
      identified, and 10 of these regions have genes that encode putative virulence
      factors or proteins mediating antibiotic resistance. We find that lateral gene
      transfer has played a fundamental role in the evolution of S. aureus. The mec
      gene has been horizontally transferred into distinct S. aureus chromosomal
      backgrounds at least five times, demonstrating that methicillin-resistant strains
      have evolved multiple independent times, rather than from a single ancestral
      strain. This finding resolves a long-standing controversy in S. aureus research.
      The epidemic of toxic shock syndrome that occurred in the 1970s was caused by a
      change in the host environment, rather than rapid geographic dissemination of a
      new hypervirulent strain. DNA microarray analysis of large samples of clinically
      characterized strains provides broad insights into evolution, pathogenesis, and
      disease emergence.

PMID- 11447288
TI  - IL-7 is critical for homeostatic proliferation and survival of naive T cells.
AB  - In T cell-deficient conditions, naive T cells undergo spontaneous "homeostatic"
      proliferation in response to contact with self-MHC/peptide ligands. With the aid
      of an in vitro system, we show here that homeostatic proliferation is also
      cytokine-dependent. The cytokines IL-4, IL-7, and IL-15 enhanced homeostatic
      proliferation of naive T cells in vitro. Of these cytokines, only IL-7 was found
      to be critical; thus, naive T cells underwent homeostatic proliferation in IL-4(
      ) and IL-15(-) hosts but proliferated minimally in IL-7(-) hosts. In addition to
      homeostatic proliferation, the prolonged survival of naive T cells requires IL-7.
      Thus, naive T cells disappeared gradually over a 1-month period upon adoptive
      transfer into IL-7(-) hosts. These findings indicate that naive T cells depend on
      IL-7 for survival and homeostatic proliferation.

PMID- 11447289
TI  - Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal
      transduction pathways.
AB  - The docking protein FRS2 alpha has been implicated as a mediator of signaling via
      fibroblast growth factor receptors (FGFRs). We have demonstrated that targeted
      disruption of FRS2 alpha gene causes severe impairment in mouse development
      resulting in embryonal lethality at E7.0--E7.5. Experiments with FRS2 alpha
      deficient fibroblasts demonstrate that FRS2 alpha plays a critical role in FGF
      induced mitogen-activated protein (MAP) kinase stimulation, phosphatidylinositol
      3 (PI-3) kinase activation, chemotactic response, and cell proliferation.
      Following FGF stimulation, tyrosine phosphorylated FRS2 alpha functions as a site
      for coordinated assembly of a multiprotein complex that includes Gab1 and the
      effector proteins that are recruited by this docking protein. Furthermore, we
      demonstrate that different tyrosine phosphorylation sites on FRS2 alpha are
      responsible for mediating different FGF-induced biological responses. These
      experiments establish the central role of FRS2 alpha in signaling via FGFRs and
      demonstrate that FRS2 alpha mediates multiple FGFR-dependent signaling pathways
      critical for embryonic development.

PMID- 11447290
TI  - Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and
      vascular responses to hypoxia.
AB  - Chronic hypoxia causes pulmonary hypertension with smooth muscle cell
      proliferation and matrix deposition in the wall of the pulmonary arterioles. We
      demonstrate here that hypoxia also induces a pronounced inflammation in the lung
      before the structural changes of the vessel wall. The proinflammatory action of
      hypoxia is mediated by the induction of distinct cytokines and chemokines and is
      independent of tumor necrosis factor-alpha signaling. We have previously proposed
      a crucial role for heme oxygenase-1 (HO-1) in protecting cardiomyocytes from
      hypoxic stress, and potent anti-inflammatory properties of HO-1 have been
      reported in models of tissue injury. We thus established transgenic mice that
      constitutively express HO-1 in the lung and exposed them to chronic hypoxia. HO-1
      transgenic mice were protected from the development of both pulmonary
      inflammation as well as hypertension and vessel wall hypertrophy induced by
      hypoxia. Significantly, the hypoxic induction of proinflammatory cytokines and
      chemokines was suppressed in HO-1 transgenic mice. Our findings suggest an
      important protective function of enzymatic products of HO-1 activity as
      inhibitors of hypoxia-induced vasoconstrictive and proinflammatory pathways.

PMID- 11447291
TI  - A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks
      immunomodulatory or toxic activity.
AB  - GM1-ganglioside receptor binding by the B subunit of cholera toxin (CtxB) is
      widely accepted to initiate toxin action by triggering uptake and delivery of the
      toxin A subunit into cells. More recently, GM1 binding by isolated CtxB, or the
      related B subunit of Escherichia coli heat-labile enterotoxin (EtxB), has been
      found to modulate leukocyte function, resulting in the down-regulation of
      proinflammatory immune responses that cause autoimmune disorders such as
      rheumatoid arthritis and diabetes. Here, we demonstrate that GM1 binding,
      contrary to expectation, is not sufficient to initiate toxin action. We report
      the engineering and crystallographic structure of a mutant cholera toxin, with a
      His to Ala substitution in the B subunit at position 57. Whereas the mutant
      retained pentameric stability and high affinity binding to GM1-ganglioside, it
      had lost its immunomodulatory activity and, when part of the holotoxin complex,
      exhibited ablated toxicity. The implications of these findings on the mode of
      action of cholera toxin are discussed.

PMID- 11447292
TI  - Lightness constancy in primary visual cortex.
AB  - When the illumination of a visual scene changes, the quantity of light reflected
      from objects is altered. Despite this, the perceived lightness of the objects
      generally remains constant. This perceptual lightness constancy is thought to be
      important behaviorally for object recognition. Here we show that interactions
      from outside the classical receptive fields of neurons in primary visual cortex
      modulate neural responses in a way that makes them immune to changes in
      illumination, as is perception. This finding is consistent with the hypothesis
      that the responses of neurons in primary visual cortex carry information about
      surface lightness in addition to information about form. It also suggests that
      lightness constancy, which is sometimes thought to involve "higher-level"
      processes, is manifest at the first stage of visual cortical processing.

PMID- 11447293
TI  - The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with
      proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and
      possesses in vitro E3 ubiquitin ligase activity.
AB  - The infected cell protein 0 (ICP0) of herpes simplex virus 1, a promiscuous
      transactivator shown to enhance the expression of genes introduced into cells by
      infection or transfection, interacts with numerous cellular proteins and has been
      linked to the disruption of ND10 and degradation of several proteins. ICP0
      contains a RING finger domain characteristic of a class of E3 ubiquitin ligases.
      We report that: (i) in infected cells, ICP0 interacts dynamically with
      proteasomes and is bound to proteasomes in the presence of the proteasome
      inhibitor MG132. Also in infected cells, cdc34, a polyubiquitinated E2 ubiquitin
      conjugating enzyme, exhibits increased ICP0-dependent dynamic interaction with
      proteasomes. (ii) In an in vitro substrate-independent ubiquitination system, the
      RING finger domain encoded by exon 2 of ICP0 binds cdc34, whereas the carboxyl
      terminal domain of ICP0 functions as an E3 ligase independent of the RING finger
      domain. The results indicate that ICP0 can act as a unimolecular E3 ubiquitin
      ligase and that it promotes ubiquitin-protein ligation and binds the E2 cdc34. It
      differs from other unimolecular E3 ligases in that the domain containing the RING
      finger binds E2, whereas the ligase activity maps to a different domain of the
      protein. The results also suggest that ICP0 shuttles between nucleus and
      cytoplasm as a function of its dynamic interactions with proteasomes.

PMID- 11447294
TI  - Polo-like kinase is required for the fragmentation of pericentriolar Golgi stacks
      during mitosis.
AB  - The pericentriolar stacks of Golgi cisternae undergo extensive reorganization
      during mitosis in mammalian cells. GM130 and GRASP65 (Golgi reassembly stacking
      protein of 65 kDa) are Golgi-associated proteins that are targets of mitotic
      kinases, and they have also been implicated in the reorganization of the Golgi
      structure during cell division. Previous studies have reported that mitogen
      activated protein kinase kinase-1 (MEK1) and Cdc2 protein kinases are involved in
      these dynamic changes in the Golgi structure. More recently, the mitotic polo
      like kinase (Plk) has been shown to interact with and phosphorylate GRASP65.
      Here, we provide evidence that Plk is involved in the mitosis-specific
      fragmentation of the Golgi apparatus. The addition of kinase-defective Plk or
      immunodepletion of Plk disrupts the fragmentation process. Furthermore, Golgi
      fragmentation is inhibited by the addition of either full-length or truncated
      GRASP65. These findings suggest that phosphorylation of GRASP65 by Plk may be a
      critical event in the reorganization of the Golgi structure during mitosis.

PMID- 11447296
TI  - A hebbian form of long-term potentiation dependent on mGluR1a in hippocampal
      inhibitory interneurons.
AB  - Hippocampal inhibitory interneurons play important roles in controlling the
      excitability and synchronization of pyramidal cells, but whether they express
      long-term synaptic plasticity that contributes to hippocampal network function
      remains uncertain. We found that pairing postsynaptic depolarization with theta
      burst stimulation induced long-term potentiation (LTP) of putative single-fiber
      excitatory postsynaptic currents in interneurons. Either postsynaptic
      depolarization or theta-burst stimulation alone failed to induce LTP. LTP was
      expressed as a decrease in failure rates and an increase in excitatory
      postsynaptic current amplitude, independent of N-methyl-d-aspartate receptors,
      and dependent on metabotropic glutamate receptors subtype 1a. LTP was induced
      specifically in interneurons in stratum oriens and not in interneurons of stratum
      radiatum/lacunosum-moleculare. Thus, excitatory synapses onto specific subtypes
      of inhibitory interneurons express a new form of hebbian LTP that will contribute
      to hippocampal network plasticity.

PMID- 11447298
TI  - Unfettered access to published results.

PMID- 11447297
TI  - Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein
      promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic
      effect in Fas-induced cell death.
AB  - The inhibitor of apoptosis (IAP) family of anti-apoptotic proteins regulate
      programmed cell death and/or apoptosis. One such protein, X-linked IAP (XIAP),
      inhibits the activity of the cell death proteases, caspase-3, -7, and -9. In this
      study, using constitutively active mutants of caspase-3, we found that XIAP
      promotes the degradation of active-form caspase-3, but not procaspase-3, in
      living cells. The XIAP mutants, which cannot interact with caspase-3, had little
      or no activity of promoting the degradation of caspase-3. RING finger mutants of
      XIAP also could not promote the degradation of caspase-3. A proteasome inhibitor
      suppressed the degradation of caspase-3 by XIAP, suggesting the involvement of a
      ubiquitin-proteasome pathway in the degradation. An in vitro ubiquitination assay
      revealed that XIAP acts as a ubiquitin-protein ligase for caspase-3. Caspase-3
      was ubiquitinated in the presence of XIAP in living cells. Both the association
      of XIAP with caspase-3 and the RING finger domain of XIAP were essential for
      ubiquitination. Finally, the RING finger mutants of XIAP were less effective than
      wild-type XIAP at preventing apoptosis induced by overexpression of either active
      form caspase-3 or Fas. These results demonstrate that the ubiquitin-protein
      ligase activity of XIAP promotes the degradation of caspase-3, which enhances its
      anti-apoptotic effect.

PMID- 11447299
TI  - Endothelin receptor antagonist.

PMID- 11447300
TI  - Therapeutic role of bosentan in hypertension: lessons from the model of
      perinephritic hypertension.
AB  - Since its discovery in 1988, there has been increasing evidence that endothelin-1
      (ET-1) plays an important role in the pathophysiology of hypertension and its
      related end-organ damages. First studies, using ET-1 administration in animals or
      in humans suspected this role by demonstrating the hypertensive properties of ET
      1. The latter, due to stimulation of ET(A) receptors inducing sustained
      vasoconstriction have been reported to follow transient vasodilation linked with
      activation of an endothelial ET(B) receptor releasing nitric oxide (NO). In
      certain instances, ET(B) smooth-muscle receptors might also induce contraction.
      Cloning of these receptors helped to develop ET-1 receptor antagonists. As soon
      as one of them became available, bosentan, a dual (ET(A) and ET(B)) ET-1 receptor
      antagonist, we tested its effects in the canine model of perinephritic
      hypertension. Bosentan was found to exert striking hypotensive effects, due to
      peripheral vasodilation but without affecting cardiac function. In further
      experiments, we observed that effects of bosentan were additional to those of ACE
      inhibitors or angiotensin II antagonists. This opened new therapeutic
      perspectives and also suggested a proper role of ET-1 in hypertension,
      independent of the renin-angiotensin system. To explain this role, we
      demonstrated a real imbalance characterized by an impairment of the NO system in
      favor of the ET-1 pathway. Recent studies suggest that such an imbalance may also
      occur in human hypertension. Furthermore, the contribution of ET-1 to human
      hypertension appears more convincing since bosentan was shown to decrease blood
      pressure in hypertensive subjects. Finally, ET-1 receptor antagonists might be of
      therapeutic interest to prevent hypertension induced end-organ damages. Whether
      or not these compounds are able to prevent or to reverse target organ injuries in
      man remains to be investigated.

PMID- 11447301
TI  - Crosstalk between endothelin and nitric oxide in the control of vascular tone.
AB  - Several lines of evidence indicate that nitric oxide (NO) impairs endothelin (ET)
      production/action in vitro. Acute pressor responses caused by the blockade of NO
      formation with arginine analogues in vivo are blunted by selective ET(A) or dual
      ET(A)/ET(B) receptor blockade whereas blockade of NO formation magnifies ET
      induced constriction of various vascular territories. Given that ET receptor
      blockade has normally limited effects on mean arterial pressure, the reversal of
      pressor responses caused by the blockade of NO formation with ET receptor
      blockade most likely reflects a significant crosstalk between NO and ET.
      Suppression of NO formation also leads to significant increases in ET production
      caused by agents targeting the endothelium, such as acetylcholine and thrombin.
      In addition, the inhibitory effect of shear stress on endothelial cells ET
      production also involves NO as an intermediate.Paradoxically, chronic exposure to
      organic nitrates which causes nitrate tolerance leads to an augmented vascular ET
      content. An increased angiotensin II (AII) production is apparently pivotal in
      this process. This article reviews observations pointing to the importance of
      NO/ET interactions as a fundamental and common regulatory mechanism shared across
      species. As a consequence of this crosstalk between NO and ET, experimental
      strategies designed to assess endothelial NO-dependent activity by the blockade
      of NO formation may be mitigated by magnified ET-dependent influences.

PMID- 11447302
TI  - Role of endothelin in the control of peripheral vascular tone in human
      hypertension.
AB  - Endothelins are potent 21 amino acid vasoconstrictor isopeptides produced in
      different vascular tissues, including vascular endothelium. Endothelin-1 is the
      main endothelin generated by the endothelium and probably the most important in
      the cardiovascular system. Endothelin-1 acts through specific receptors termed
      ET(A), represented only on smooth muscle cells and having the function of growth
      promotion and mediating contractions, and ET(B), located both on smooth muscle
      cells, where they evoke contractions, and on endothelial cells, inducing
      relaxation by production of the endothelium-derived relaxing factor nitric oxide.
      In physiological conditions endothelin-1 administration causes vasodilation and
      vasoconstriction at low and high concentrations, respectively. However,
      administration of mixed ET(A)/(B) receptor antagonists causes slight or absent
      vasodilation, indicating that the direct vasoconstrictor effect of the peptide is
      probably masked by ET(B)-induced NO-dependent vasodilation. In essential
      hypertensive patients, the activity of exogenous endothelin-1 is either
      increased, similar or decreased as compared to normotensive subjects, depending
      on which vascular district or scheme of administration is considered. But
      although available evidence does not indicate increased endothelin-1 plasma
      levels in patients with essential hypertension, simultaneous antagonism of
      ET(A)/(B) receptors causes a greater degree of vasodilation in hypertensives than
      in normotensive subjects. Moreover administration of a selective ET(B) receptor
      antagonist causes vasoconstriction in normotensive subjects and vasodilation in
      essential hypertensive patients. Finally, the vasodilating effect of a mixed
      ET(A)/(B) receptor antagonist is inversely related to NO availability. Taken
      together these findings suggest that essential hypertension is characterized by
      increased endothelin-1 vasoconstrictor tone. This alteration seems to be
      dependent on decreased endothelial ET(B)-mediated NO production attributable to
      impaired NO availability. In such conditions endothelial ET(B)-induced
      vasodilation no longer compensates for the direct classical endothelin
      vasoconstrictor effect mediated by smooth muscle cell ET(A) and ET(B) receptors.
      Therefore endothelin-1 could potentially be involved in the pathogenesis of
      essential hypertension or of its complications, and blockade of this system is a
      fascinating new target for therapeutic intervention in this disease.

PMID- 11447303
TI  - Potential role of endothelin receptor antagonists in the setting of
      cardiopulmonary bypass: relevance to myocardial performance.
AB  - The ET system is activated in cardiac surgical setting as evidenced by elevated
      systemic and myocardial ET-1 levels after coronary bypass grafting surgery which
      requires hypothermic cardioplegic arrest and cardiopulmonary bypass. Increased ET
      1 may influence a number of clinical parameters in this setting. First, ET-1 may
      directly modulate myocardial contractile performance in the early postoperative
      period resulting in LV dysfunction and a complex postoperative course. Second,
      elevated ET-1 levels may exacerbate increased pulmonary vascular resistance and
      contribute to the development of transient pulmonary hypertension following
      bypass. Finally, augmented postoperative ET-1 levels could contribute to changes
      in the caliber and flow of vascular conduits used for coronary bypass. In this
      review, a current perspective on the ET system in the setting of cardiopulmonary
      bypass grafting surgery is provided and the potential use of ET receptor
      antagonists in this setting is discussed.

PMID- 11447304
TI  - Endothelin antagonism in experimental ischemic heart failure: hemodynamic,
      structural and neurohumoral effects.
AB  - Heart failure is characterized both by an activation of the endothelin system and
      an increased vasoconstrictor contractile response to the peptide. Given its
      pharmacological profile, it is likely that endothelin (ET-1) plays a deleterious
      role in the development of heart failure, and that blockers of the endothelin
      system are beneficial in this disease. Indeed, in rats with heart failure, ET(A)
      and dual ET(A)-ET(B) receptor antagonists reduce arterial pressure as well as
      left ventricular end diastolic pressure. The same antagonists also prevent the
      degradation of left ventricular function, as evidenced by the increased left
      ventricular fractional shortening and wall thickening. ET(A) and ET(A)-ET(B)
      antagonists also reduce LV dilatation and LV fibrosis, but do not affect LV
      hypertrophy. Moreover, comparison between selective ET(A) and combined ET(A)
      ET(B) antagonists reveal no differences in terms of their effects on blood
      pressure, LV hemodynamics or remodeling. However, only combined ET(A)-ET(B)
      antagonists significantly decreased heart rate. ET(B) antagonists alone do not
      affect blood pressure or LV hemodynamics, but reduce LV fibrosis. With regard to
      survival, we have shown that long term treatment with the dual ET(A)-ET(B)
      antagonist bosentan increased survival to the same extent as an angiotensin
      converting enzyme inhibitor. However, the effect of selective ET(A) antagonists
      on survival is more controversial, since we found that the non-peptide ET(A)
      antagonists LU 135252 did not affect survival of rats with myocardial infarction,
      while others have shown that the peptide ET(A) antagonist BQ-123 increased
      survival in the same model. These conflicting data regarding the efficacy of
      selective ET(A) vs dual ET(A)-ET(B) blockade points out the need for controlled
      long term studies comparing the effects of theses two pharmacological approaches
      on survival.

PMID- 11447306
TI  - Clinical experience with endothelin receptor antagonists in chronic heart
      failure.
AB  - Both ET(A) selective and dual, ET(A/B), receptor antagonists have favourable
      short- and longer-term haemodynamic actions in patients with acute and chronic
      heart failure. Their effect on neurohumoral measures is not yet fully determined.
      Two moderately large, medium-duration studies have examined the effect of dual
      ET(A/B) receptor antagonists on clinical status, reaching conflicting
      conclusions. One large scale, long-term, morbidity mortality evaluation is
      underway with bosentan.

PMID- 11447305
TI  - Endothelin A receptor antagonists in congestive heart failure: blocking the beast
      while leaving the beauty untouched?
AB  - Congestive heart failure (CHF) is a disease process characterized by impaired
      left ventricular function, increased peripheral and pulmonary vascular resistance
      and reduced exercise tolerance and dyspnea. Thus, mediators involved in the
      control of myocardial function and vascular tone may be involved in its
      pathophysiology. The family of endothelins (ET) consists of four closely related
      peptides, ET-1, ET-2, ET-3, and ET-4, which cause vasoconstriction, cell
      proliferation, and myocardial effects through activation of ET(A) receptors. In
      contrast, endothelial ET(B) receptors mediate vasodilation via release of nitric
      oxide and prostacyclin. In addition, ET(B) receptors in the lung are a major
      pathway for the clearance of ET-1 from plasma. Thus, infusion of an ET(A)
      receptor antagonist into the brachial artery in healthy humans leads to
      vasodilation whereas infusion of an ET(B) receptor antagonist causes
      vasoconstriction. ET-1 plasma levels are elevated in CHF and correlate both with
      the hemodynamic severity and with symptoms. Plasma levels of ET-1 and its
      precursor, big ET-1, are strong independent predictors of death in patients after
      myocardial infarction and with CHF. ET-1 contributes to increased systemic and
      pulmonary vascular resistance, vascular dysfunction, myocardial ischemia, and
      renal impairment in CHF. Selective ET(A) as well as combined ET(A/B) receptor
      antagonists have been studied in patients with CHF showing impressive hemodynamic
      improvements (i.e. reduced peripheral vascular and pulmonary resistance as well
      as increased cardiac output). These results indicate that ET receptor antagonists
      indeed have a potential to improve hemodynamics, symptoms, and potentially
      prognosis of CHF which still carries a high mortality.

PMID- 11447307
TI  - Hemodynamic effects of bosentan in patients with chronic heart failure.
AB  - A role of the potent and long-acting vasoconstrictor peptide endothelin-1 and the
      pathophysiology of chronic human heart failure has been postulated based upon
      indirect evidence such as elevated plasma endothelin-1 levels and their with the
      degree of hemodynamic impairment. The advent of specific of endothelin-1 receptor
      antagonists has provided the opportunity not only to directly evaluate its
      pathophysiological role but also to assess its potential role as a new approach
      to heart failure therapy. This brief review summarizes the evidence linking
      endothelin-1 to the pathophysiology of chronic heart failure and the clinical
      results obtained in patients during acute, intravenous and more prolonged, oral
      administration with bosentan, a mixed ET(A)/ET(B)-receptor antagonist. Bosentan
      acutely and during short-term oral therapy markedly improved hemodynamics in
      patients in addition to standard heart failure therapy, including an ACE
      inhibitor. These effects were associated with a reduced responsiveness of the
      renin-angiotensin system to diuretic therapy and reduced basal plasma aldosterone
      levels. Although the hemodynamic and neurohumoral profile of short-term bosentan
      therapy looks promising for the treatment of patients with chronic heart failure
      appropriate trials will have to be performed to document clinical benefit during
      long-term therapy. Finally, the question remains open whether mixed endothelin-1
      receptor antagonists like bosentan will have similar effects as compared to
      antagonists which block the ET(A) receptor only.

PMID- 11447308
TI  - Endothelin and heart failure.
AB  - The availability of potent and orally active nonpeptide endothelin (ET) receptor
      antagonists has generated a host of information on the pathophysiological role of
      ET-1 in a number of preclinical models including hypertension, renal failure,
      heart failure and pulmonary hypertension. Convincing data are available to show
      that ET-1 receptor antagonists are beneficial in humans as far as reversal of
      deranged systemic and regional hemodynamics associated with CHF and pulmonary
      hypertension. As in other disease areas, the issue of whether ET(A)-selective or
      ET(A/B) antagonists are more suited for CHF treatment remains unresolved. ET(B)
      receptors may mediate some critical processes in the kidney such as sodium and
      water excretion in addition to releasing vasodilator substances such as NO and
      prostacyclin from endothelial cells. In heart failure and chronic renal diseases,
      preservation of ET(B)-mediated responses in the kidney and pulmonary endothelium
      might be beneficial. On the other hand, blockade of ET(B)-mediated
      vasoconstriction, smooth muscle cell proliferation and fibrosis by ET(B)
      antagonists might be beneficial. In clinical trials so far, the hemodynamic
      effects of mixed antagonists of ET receptors and ET(A) selective antagonists seem
      equivalent.

PMID- 11447309
TI  - Diagnostic and therapeutic potential of the endothelin system in patients with
      chronic heart failure.
AB  - There is now considerable evidence to support a role for the endothelin (ET)
      system in the pathogenesis and progression of chronic heart failure (CHF). As
      such, the potential exists for this system to be useful in both diagnosis (by
      measurement of peptide levels in plasma and other body fluids) and treatment (by
      pharmacological blockade) of this condition. Plasma levels of endothelin-1 (ET-1)
      are elevated in CHF and the magnitude of elevation correlates with disease
      severity. ET-1 levels in plasma predict subsequent mortality in patients with
      CHF. ET-1 may also contribute to symptoms associated with CHF, such as exercise
      intolerance. In the diagnosis of CHF, plasma levels of ET-1 appear to be a less
      powerful discriminator between patients with mild disease and control subjects
      with normal ventricular function on multivariate analyses, compared to brain
      natriuretic peptide (BNP), or its N-terminal fragment. ET-1 concentrations are
      also elevated in the saliva of patients with CHF and may represent an alternative
      approach to assessment of the status of the ET system in these patients. Specific
      ET receptor antagonists (both mixed and ET(A)-selective) have been developed.
      Studies with these agents in animal models of CHF have demonstrated beneficial
      effects via both haemodynamic and non-haemodynamic pathways. A number of short
      term clinical studies have been performed demonstrating improvements in
      haemodynamic parameters without neurohormonal activation. Long-term clinical
      studies with ET receptor antagonists are currently underway to definitively test
      the impact of blockade of this system on mortality and major cardiovascular
      endpoints. Endothelin converting enzyme (ECE) inhibitors represent an alternative
      strategy of ET blockade, and early data from animal models suggest these agents
      may be of clinical utility, either alone or, more likely, in combination with
      other zinc metallopeptidases.

PMID- 11447310
TI  - Huperzine A protects rat pheochromocytoma cells against oxygen-glucose
      deprivation.
AB  - The effect of huperzine A (HupA) on oxygen-glucose deprivation (OGD)-induced
      injury was investigated in the rat pheochromocytoma cell line PC12. OGD for 3 h
      and reoxygenation for 24 h triggered apoptosis characterized by chromatin
      condensation, nucleus fragmentation and DNA laddering. The temporal profile of c
      jun, p53, bcl-2 and bax mRNA after OGD indicated that these genes played
      important roles in apoptosis. Pre-incubation of the cells for 2 h with 1 microM
      HupA significantly attenuated apoptosis. The same treatment also reduced the up
      regulation of c-jun and bax as well as the down-regulation of bcl-2. These data
      suggest the ability of HupA to attenuate apoptosis induced by OGD may result from
      its capability to alter the expression of apoptosis-related genes.

PMID- 11447311
TI  - NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat
      neuropathic pain model.
AB  - Pro-inflammatory cytokines have been shown to be involved in the genesis,
      persistence, and severity of neuropathic pain following nerve injury. The
      transcription factor, nuclear factor-kappa B (NF-kappaB), plays a pivotal role in
      regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF
      kappaB in the pathogenesis of neuropathic pain, using a gene-based approach of NF
      kappaB decoy, we tested whether the activated NF-kappaB affected pain behavior
      via the expression of inflammatory mediators. Single endoneurial injections of NF
      kappaB decoy, at the site of nerve lesion, significantly alleviated thermal
      hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the
      inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury.
      This finding suggests that a perineural inflammatory cascade, that involves NF
      kappaB, is involved in the pathogenesis of neuropathic pain.

PMID- 11447312
TI  - Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in
      human tauopathies and synucleinopathies.
AB  - We examined the immunoreactivity of ubiquitin-binding protein p62 and its
      association with ubiquitin (Ub), alpha-synuclein, and paired helical filament
      (PHF)-tau in the affected brain areas of human tauopathies and synucleinopathies.
      Ubiquitin-binding protein p62 is a widely expressed protein that can bind to Ub
      noncovalently and is involved in several signalling pathways, making p62 a
      candidate regulator of Ub-mediated proteolysis. We show that p62 immunoreactivity
      co-localizes with neuronal and glial Ub-containing inclusions in Alzheimer's
      disease, Pick's disease, dementia with Lewy bodies, Parkinson's disease, and
      multiple system atrophy. This is the first demonstration of a common protein
      component, apart from Ub, that is present in both PHF-tau and alpha-synuclein
      inclusions. In both tauo- and synucleinopathies, the staining patterns for p62
      and Ub were markedly similar, suggesting that a common mechanism which requires
      interaction of p62 and Ub contributes to the formation of PHF-tau and alpha
      synuclein inclusions.

PMID- 11447313
TI  - Systemic morphine reduces the wind-up of trigeminal nociceptive neurons.
AB  - We assessed the effects of intravenous morphine on the wind-up of nociceptive
      neurons of the spinal trigeminal nucleus oralis (Sp5O). Extracellular recordings
      of Sp5O nociceptive convergent neurons were performed in intact halothane
      anesthetized rats. Wind-up of C-fiber-evoked responses was elicited by repetitive
      electrical stimulation (train of 16 shocks, 0.66 Hz) of their receptive field at
      C-fiber intensity (3 times the threshold). Wind-up was tested for its sensitivity
      to morphine (6 mg/kg,i.v.), and the specificity of the effects was verified with
      naloxone (0.4 mg/kg, i.v.). Nineteen convergent neurons displaying wind-up were
      recorded. Morphine reduced the wind-up of all but one. In five cases,
      notwithstanding a reduced wind-up, the neuronal response evoked by the first
      stimulus in the train (initial input) was unexpectedly increased. Naloxone always
      antagonized morphine inhibitory effects on the wind-up. When administered
      systemically, morphine reduced the wind-up of trigeminal nociceptive neurons.
      This inhibitory effect occurred independently of morphine's ability to affect the
      initial C-fiber-evoked input. Our findings support the idea that systemic
      morphine probably blocks wind-up by acting at opioid receptors located
      postsynaptically to nociceptive primary afferents.

PMID- 11447314
TI  - Modulation of CGRP and PGE2 release from isolated rat skin by alpha-adrenoceptors
      and kappa-opioid-receptors.
AB  - Norepinephrine (NE) reduces the release of neuropeptides from central terminals
      of primary afferent neurones by presynaptic inhibition. We investigated whether
      NE also affects stimulus-induced intracutaneous calcitonin gene-related peptide
      (CGRP) and secondary prostaglandin E2 (PGE2) release. For comparison, kappa
      opioid effects were examined. Antidromic electrical nerve stimulation resulted in
      significant increases in the release of CGRP and PGE2. The PGE2 release was
      prevented by selective activation of alpha2-adrenoceptors whereas the CGRP
      release was not changed. In contrast, selective kappa-opioid receptor activation
      diminished electrically evoked release of both CGRP and PGE2. We conclude that NE
      affected stimulated PGE2 release via alpha2-adrenoceptors on cells other than
      cutaneous afferents while kappa-opioid receptors are expressed in peripheral
      terminals of cutaneous afferents and their activation reduced CGRP release and
      secondary PGE2 formation.

PMID- 11447315
TI  - Modulation of visual perception by eye gaze direction in patients with spatial
      neglect and extinction.
AB  - Parietal neurons have retinotopic receptive fields whose response is modulated by
      eye gaze signals. We examined the role of eye position and eye movement direction
      on visual extinction in three patients with parietal damage and left neglect,
      characterized by impaired perception of contralesional field stimuli despite
      intact visual cortex. Patients tracked a horizontally moving fixation point,
      while discriminating fine changes at the fixated point and detecting more salient
      targets flashed on either side of fixation. Eye position modulated extinction,
      with worse detection of left field targets during eccentric fixation towards the
      left. Direction of eye movement also modulated extinction, with worse detection
      of left targets during rightward scanning. These results demonstrate that
      extinction in contralesional field is influenced by extra-retinal factors related
      to eye position and eye movements, consistent with a convergence of these signals
      in parietal cortex.

PMID- 11447316
TI  - Somatostatin type 2 receptor expression in the rat hippocampus following cerebral
      ischemia.
AB  - We examined how transient cerebral ischemia affects the mRNA expression, and the
      immunoreactive distribution, of the somatostatin type 2 (sst2) receptor in the
      adult rat hippocampus. Following reperfusion, sst2 mRNA levels increased
      significantly in the CA1 region by 3 h, and were also increased in the CA3 and
      CA4/hilus subfields at 6 and 12 h. At 24 h, however, sst2 receptor mRNA levels
      returned to baseline throughout the hippocampus. At the protein level, we found
      the regional immunoreactivity of the sst2a receptor was maintained, or slightly
      elevated, throughout the hippocampus at 6 h, but not different from control at 24
      h. These results suggest that sst2 receptors maintain their normal distribution
      and prevalence in the post-ischemic hippocampus before the deterioration of the
      vulnerable CA1 neurons. Thus, they represent attractive targets for
      neuroprotective interventions.

PMID- 11447317
TI  - Disruption of focal adhesions mediates detachment during neuronal apoptosis.
AB  - Apoptosis participates in the development of the nervous system and in
      neurodegeneration. The aim of this study was to investigate the mechanisms of
      detachment of neuronal cells from the extracellular matrix (ECM) during
      apoptosis. Detachment of Ntera2 neuronal cells was accompanied by decreased
      surface expression of the beta1 integrin and redistribution of proteins from
      focal adhesions (FA). FA proteins were cleaved in a discrete sequence: p130cas,
      then paxillin, then talin. Caspase inhibition prevented detachment and cleavage
      of paxillin and p130cas, whilst calpain inhibition blocked talin cleavage.
      Neuronal cells therefore detach as a result of redistribution and caspase
      dependent cleavage of focal adhesion proteins. Cleavage occurs sequentially such
      that critical ECM-integrin survival signalling cascades are severed before
      disruption of focal adhesion-cytoskeletal links.

PMID- 11447318
TI  - Orexin (hypocretin) gene expression in rat ependymal cells.
AB  - The expression of prepro-orexin (PPO) mRNA in the rat brain was investigated by
      in situ hybridization histochemistry. In the lateral and posterior hypothalamic
      areas, which are considered to produce exclusively PPO mRNA, we found high levels
      of PPO mRNA expressions. We also localized PPO mRNA hybridization signals at
      lower levels around the lateral ventricles, the third and fourth ventricle.
      Cellular analysis by emulsion autoradiography revealed the expression of PPO mRNA
      in the ependymal cell layer. Our results demonstrate that beside the lateral and
      posterior hypothalamus PPO mRNA is expressed in ependymal cells.

PMID- 11447319
TI  - Different classifications of UPOs in the parametrically different chaotic ISI
      series of a neural pacemaker.
AB  - Various interspike intervals (ISIs) in a series of spontaneous discharges of
      experimental neural pacemakers were identified as chaotic and as lying between
      stable period 2 and stable period 3. The method of So et al. for detection of
      unstable periodic orbits (UPOs) was applied to analyze two chaotic ISI series
      generated under the action of [Ca2+]o in different concentrations. In the chaotic
      ISI series near the stable period 2, an unstable period 2 orbit was detected. In
      the chaotic ISI series near the stable period 3, both an unstable period 2 orbit
      and an unstable period 3 orbit were detected. The location of the unstable period
      2 orbit was close to that of the stable period 2 in the return map, while the
      location of the unstable period 3 orbit was close to that of the stable period 3.
      The results not only revealed the structures of various chaotic ISI series, but
      also indicated that the classification of UPOs could reflect the experimental
      control parameters at which the chaotic ISI series were generated. The previously
      discovered period adding bifurcation in the ISI series generated by experimental
      neural pacemakers [12] was further described in terms of the evolution of the
      period orbits.

PMID- 11447320
TI  - Changes in endocannabinoid transmission in the basal ganglia in a rat model of
      Huntington's disease.
AB  - Recent studies have demonstrated a loss of cannabinoid CB1 receptors in the basal
      ganglia in Huntington's disease (HD), but there are no data on endocannabinoid
      levels in this disease. In the present study, we have addressed this question by
      using rats with bilateral intrastriatal injections of 3-nitropropionic acid (3
      NP), a toxin that, through the selective damage of striatal GABAergic efferent
      neurons, produces a useful model of HD. Twelve days after the lesion, 3-NP
      lesioned rats exhibited motor disturbances, characterized by an ambulatory
      hyperactivity accompanied by a loss of guided activities. Analysis of GABA
      contents in the basal ganglia showed a trend towards a reduction compatible with
      motor hyperactivity. In addition, CB1 receptor binding and, to a greater extent,
      CB1 receptor activation of GTP-binding proteins, were also reduced in the basal
      ganglia. These changes were paralleled by a decrease of the contents of the two
      endocannabinoids, anandamide and 2-arachidonoylglycerol, in the striatum, and by
      an increase, particularly of anandamide, in the ventral mesencephalon where the
      substantia nigra is located. Both CB1 receptors and endocannabinoid levels were
      not altered in the cerebral cortex, an area not affected by the lesion. In
      summary, behavioral and biochemical changes observed in rats intrastriatally
      lesioned with 3-NP were similar to those occurring in the brain of HD patients.
      As expected, a loss of CB1 receptor function was evident in the basal ganglia of
      these rats and this was accompanied by different changes in endocannabinoid
      levels.

PMID- 11447321
TI  - Anandamide-induced sleep is blocked by SR141716A, a CB1 receptor antagonist and
      by U73122, a phospholipase C inhibitor.
AB  - Anandamide (ANA) alters sleep by increasing the amount of time spent in slow wave
      sleep 2 (SWS2) and rapid eye movement sleep (REMS) at the expense of wakefulness
      (W) in rats. In this report, we describe a similar effect of ANA when injected
      itracerebroventricularly (i.c.v.) or into the peduriculopontine tegmental nucleus
      (PPTg) and the lack of an effect when ANA is administered into the medial
      preoptic area (MPOA). Furthermore, the i.c.v. or PPTg administration of
      SR141716A, a CB1 antagonist, or U73122, a PLC inhibitor, 15 min prior to ANA,
      readily prevents the ANA induced changes in sleep. The present results suggest
      that a cannabinoid system in the PPTg may be involved in sleep regulation and
      that the cannabinoid effect is mediated by the CB1 receptor coupled to a PLC
      second messenger system.

PMID- 11447322
TI  - Transfer of the apoptotic message in sister cultures of cerebellar neurons.
AB  - In vitro cultured cerebellar granule cells (cgc) undergo apoptotic death when the
      depolarising concentration of KCl 25 mM is adjusted to 5 mM. We investigated
      whether the apoptotic message can be transferred from a group of neurons to
      neighbouring but separated sister cultures by resorting to two different culture
      systems, one based on the use of concentric dishes, the other employing the
      transwells. The extent of transferred death was 38.6% in the two dishes system
      and 31.3% in the transwell system. The transfer of such death-inducing signal(s),
      accompanied by chromatin condensation, was inhibited by actinomicin D.
      Preliminary experiments aimed at identifying such apoptosis-inducing signal(s)
      suggest the involvement of beta-amyloid fragment(s).

PMID- 11447323
TI  - A single amino acid substitution in MDEG2 specifically alters desensitization of
      the proton-activated cation current.
AB  - To clarify functional roles of MDEG2 (mammalian degenerin-2), a modulatory
      subunit of proton-activated cation channels, in MDEG1/MDEG2 heteromer, we
      replaced the Gly481 residue in MDEG2 with cysteine or phenylalanine and
      characterized them electrophysiologically. Expression of MDEG1 in Xenopus oocytes
      elicited proton-activated cation currents that were rapidly desensitized. Co
      expression of MDEG1 and MDEG2 (or MDEG2-G481C) displayed similar current traces
      as MDEG1 alone. In contrast, co-expression of MDEG1 and MDEG2-G481F dramatically
      attenuated desensitization of the proton-activated currents. Interestingly, the
      G481F mutation in MDEG2 did not alter other channel properties including maximal
      whole-cell currents, ionic selectivity, pH-sensitivity and affinity for
      amiloride. Thus, Gly481 in MDEG2 specifically controls inactivation process of
      the MDEG1/MDEG2 channel.

PMID- 11447324
TI  - Apoptosis and dendritic dysfunction precede prion protein accumulation in 87V
      scrapie.
AB  - The sequence of events involved in the neurodegeneration caused by transmissible
      spongiform encephalopathies (TSEs) is not yet known. Using a murine scrapie model
      in which neurodegeneration in the hippocampus is restricted to CA2, we show that
      pyramidal neuron damage and death by an apoptotic mechanism occur early in the
      incubation period, prior to the appearance of CA2 disease-specific accumulation
      of PrP and the onset of clinical disease. We suggest that the initial hippocampal
      pathological event in this model is dendritic dysfunction and activation of an
      apoptotic pathway rather than PrP accumulation.

PMID- 11447325
TI  - The MC4 receptor mediates alpha-MSH induced release of nucleus accumbens
      dopamine.
AB  - Strong evidence suggests a functional link between the melanocortin and dopamine
      systems. alpha-Melanocyte stimulating hormone (alpha-MSH) induced grooming
      behaviour, which can be blocked by dopamine receptor antagonists, is associated
      with increased dopaminergic transmission in the striatal regions. Whether this
      effect is mediated specifically by melanocortin (MC) receptors has not previously
      been established. Using in vivo microdialysis on anesthesized rats we have shown
      that alpha- MSH administered into the ventral tegmental area induced a
      significant increase in dopamine and DOPAC levels in the nucleus accumbens. This
      increase was completely blocked by pre-treatment with the MC4 receptor selective
      antagonist HS131, indicating that the effects of alpha-MSH on dopamine
      transmission may be mediated by the MC4 receptor.

PMID- 11447326
TI  - Functional compensation of the left dominant insula for language.
AB  - The left dominant insula was recently described as an essential area of speech,
      inducing definitive language disturbances when injured. We describe a patient
      with mild dysphasia, harboring a left insular glioma. A functional MRI found
      activations within the left inferior and middle frontal gyri, superior temporal
      gyrus, basal ganglia, but not in the insula. Surgery was performed using
      intraoperative electrical mapping in the awake patient, identifying the same
      language sites as showed by fMRI. A complete glioma resection was then performed.
      Despite an entire dominant insula removal, the patient presented no postoperative
      deficit, and even recovered from the preoperative dysphasia. This case
      illustrates the brain ability to maintain normal language without the left
      insula. The mechanisms of compensation are discussed.

PMID- 11447327
TI  - Unscheduled DNA synthesis in rat adult myenteric neurons: an immunohistochemical
      study.
AB  - Unscheduled DNA synthesis refers to DNA synthesis not followed by cell division.
      Previous studies have suggested that this phenomenon may occur in neurons from
      peripheral myenteric ganglia in conditions of functional hyperstimulation. In
      order to verify these observations, we have carried on an immunohistochemical
      study on myenteric neurons from the hypertrophic intestinal loops upstream from a
      partial obstruction (an experimental condition that induces a relevant increase
      of the neuronal workload) after labelling with two different markers: the
      proliferating cell nuclear antigen (PCNA), that is specifically expressed in cell
      nuclei during the S-phase, and the protein gene product 9.5 (PGP 9.5), a specific
      marker of nerve cells. While no myenteric neuron immunopositive for the anti-PCNA
      antibody was found in the control intestine, in the hypertrophic myenteric
      ganglia some neurons were positive for PCNA. These results provide an unequivocal
      evidence on the existence of unscheduled DNA synthesis in myenteric neurons from
      the hypertrophic intestine.

PMID- 11447328
TI  - Activation of NG2-positive oligodendrocyte progenitor cells during post-ischemic
      reperfusion in the rat brain.
AB  - This study examines the alteration of oligodendrocyte progenitor cells which
      express membrane NG2 chondroitin sulfate proteoglycan after focal ischemia in the
      rat brain. Adult male Sprague-Dawley rats were subjected to 90 min occlusion of
      the middle cerebral artery, followed by reperfusion time of up to 2 weeks. The
      distribution and morphological changes in NG2-positive oligodendrocyte progenitor
      cells were immunohistochemically examined. Stellate-shaped NG2-positive cells
      with multiple branched processes were detected in both the gray and white matter
      of normal brain. After 2 weeks of reperfusion, NG2-positive cells in the area
      surrounding the infarction site (peri-infarct area) clearly showed enlarged cell
      bodies with hypertrophied processes. These stained strongly for NG2. Although the
      number of NG2-positive cells was increased significantly in the peri-infarct
      area, it decreased markedly in the infarct core compared to controls. Double
      immunostaining revealed that these NG2-positive cells were neither astrocytes nor
      microglia, but NG2-positive oligodendrocyte progenitor cells. These progenitor
      cells are known to differentiate into oligodendrocytes. As such, this
      upregulation of NG2 expression may be an adaptive mechanism attempting to
      remyelinate rat brain tissue after ischemic insult. Only further study will
      elucidate this hypothesis.

PMID- 11447329
TI  - Magnesium potentiation of the function of native and recombinant GABA(A)
      receptors.
AB  - Mg2+ decreased basal and GABA-inhibited t-butylbicyclophosphoro[35S]thionate
      binding to GABAA receptor ion channels in rat brain sections up to 1 mM, but
      increased the binding at 10 mM. The Mg2+-effect was detectable in the presence of
      a specific GABA site competitive antagonist. Two-electrode voltage clamp
      recordings of recombinant alpha1beta2gamma2S, alpha1beta2, alpha2beta2gamma2S and
      alpha2beta2 GABAA receptors revealed a potentiation by 0.1-1 mM Mg2+ of EC20 GABA
      evoked ion currents. At 10 mM, Mg2+ decreased the currents. In the absence of
      GABA, Mg2+ did not evoke any currents. The results show that physiologically
      relevant Mg2+ concentrations affect the GABA responses on GABAA receptors in
      native and the main recombinant receptor subtypes, suggesting putative Mg2+
      binding sites on the receptor complex.

PMID- 11447330
TI  - Down-regulation of the rat serotonin transporter upon exposure to a selective
      serotonin reuptake inhibitor.
AB  - The serotonin transporter (SERT) terminates serotonergic neurotransmission by
      rapid reuptake of 5-hydroxytryptamine (5-HT) into the nerve terminal or axonal
      varicosities. SERT represents the target of various antidepressants which inhibit
      5-HT transport and are widely used for the pharmacotherapy of depression. Here,
      we have analyzed the function of SERT stably expressed in HEK 293 cells upon
      exposure to citalopram, a selective serotonin reuptake inhibitor (SSRI), with
      respect to 5-HT transport activity and protein expression as estimated by ligand
      binding experiments. Our results show that long-term exposure to an SSRI causes a
      down-regulation of transport activity as revealed by a reduction of the maximal
      transport rate, without affecting substrate affinity, accompanied by a decrease
      in ligand binding sites.

PMID- 11447331
TI  - Thumb invariance during prehension movement: effects of object orientation.
AB  - The aim of the present study was to examine the contribution of the thumb and
      index finger during the task of reaching to grasp a cylinder positioned at
      different orientations. To this end an axis was defined between a marker
      positioned on the subjects' wrist and the target. For each frame the
      perpendicular distances of the thumb and index finger from this axis were
      determined. The perpendicular distance was greater for the index finger than the
      thumb, confirming a relative stability of the thumb during natural prehension and
      supporting the notion of the thumb as a guide for the transport component of
      reaching. Further, index finger perpendicular distance was varied according to
      object orientation. When the object was positioned at an angle that requires hand
      pronation, the perpendicular distance for the index finger was the greatest. It
      is concluded that changes in the index finger distance are necessary to allow the
      thumb to maintain stability in order to provide appropriate movement guidance.

PMID- 11447332
TI  - Glucocorticoid and type 1 interferon interactions at the blood-brain barrier:
      relevance for drug therapies for multiple sclerosis.
AB  - The pharmacological effect of glucocorticoids and type 1 interferons (IFNs),
      simultaneously used as therapeuticals for multiple sclerosis (MS), on the
      (inflamed) blood-brain barrier (BBB) was investigated in vitro. Although both
      drugs additively decreased BBB permeability, they did not prevent the increase in
      BBB permeability induced by lipopolysaccharide (LPS), which served as a pro
      inflammatory stimulus. The beneficial clinical effect of glucocorticoid and IFN
      therapy for MS seems there- fore not to be mediated through a direct action at
      the level of the BBB. Most strikingly, however, pretreatment with type 1 IFNs
      (alpha and beta) potentiated the effect of glucocorticoids by two orders of
      magnitude. This lead us to hypothesize that type 1 IFNs may restore the
      dysfunctional T-helper 1 (Th1)/Th2 balance associated with MS, by a mechanism
      that involves an increased sensitivity for glucocorticoids.

PMID- 11447333
TI  - The antidepressant imipramine inhibits the M-type K+ current in rat sympathetic
      neurons.
AB  - This study aimed to assess the effects of the antidepressant drug imipramine
      (IMI) on the neuronal M-type K+ current (IK(M)). We show that IMI reversibly
      reduces IK(M) with an IC50 of 7 microM. The V0.5 and slope factor of the steady
      state activation curve remained unchanged after IMI, indicating a mode of action
      that is voltage insensitive for blocking the M-channel. Patch pipette application
      of IMI elicits same inhibitory response suggesting a binding site on the M
      channel accessible from both sides of the cell membrane. Accordingly, the
      inhibitory effect of IMI is larger by rising external pH near to the pKa of the
      drug. Therefore, we propose that a neutral form of IMI binds more efficiently to
      M-channels to exert its inhibitory action by a voltage-independent mechanism.

PMID- 11447334
TI  - Baicalein protects cortical neurons from beta-amyloid (25-35) induced toxicity.
AB  - Accumulation of amyloid beta peptide (Abeta) has been suggested to contribute to
      neurodegeneration in Alzheimer's disease (AD). Since chronic inflammation occurs
      in AD pathogenesis and lipoxygenases are important mediators of inflammatory
      processes, we evaluated the effect of lipoxygenase inhibitors on apoptosis
      induced by Abeta on rat cortical cells. The 12-lipoxygenase inhibitor baicalein
      attenuated both neuronal apoptosis and c-jun protein over-expression induced by
      Abeta(25- 35), whereas no protection was found with the broad spectrum
      lipoxygenase inhibitor nordihydroguaiaretic acid or the 5-lipoxygenase inhibitor
      caffeic acid. These results suggest that 12-lipoxygenase participates in a c-jun
      dependent apoptosis pathway triggered by Abeta(25-35), and that specific 12
      lipoxygenase inhibitors might be of interest in AD.

PMID- 11447335
TI  - Miniature postsynaptic currents depend on Ca2+ released from internal stores via
      PLC/IP3 pathway.
AB  - Miniature postsynaptic currents (mPSCs) were examined on autaptic innervation of
      single rat retinal ganglion cells in low density cultures. Removal of Ca2+ from
      bath solution or blocking of Ca2+ channels by Cd2+ had no detectable effect on
      mPSC frequency or amplitude. Thapsigargin, an agent for mobilization of Ca2+ from
      internal stores, increased mPSC frequency 3-5-fold in control, Ca2+-free or Cd2+
      containing solutions. The inositol 1,4,5-triphosphate (IP3) receptor antago-
      nist, heparin; the phospholipase C (PLC) inhibitor, U73122; and caffeine
      abolished mPSC or decreased mPSCs frequency. Calcium imaging showed that
      cytosolic Ca2+ was increased by thapsigargin and decreased by caffeine. These
      data demonstrate that internal store-released Ca2+ regulated by the PLC/IP3/IP3
      receptor pathway has critical contribution to generation and control of miniature
      release in retinal ganglion cells.

PMID- 11447336
TI  - Mismatch negativity is unaffected by top-down predictive information.
AB  - The mismatch negativity (MMN) event-related brain potential is assumed to reflect
      a stimulus-driven change detection process. We examined whether MMN is sensitive
      to volitional control by testing whether MMN is affected by the subject's
      foreknowledge of the sound changes. Subjects were instructed to produce a
      sequence of button presses by pressing one button frequently and another
      infrequently. In the predictable condition, the frequently pressed button
      triggered the standard tone, the other button the deviant tone. In the
      unpredictable condition, each button press triggered the next tone of a
      prearranged standard/deviant sequence. No difference was found in the MMN
      amplitude, latency, or scalp distribution between the predictable and
      unpredictable conditions. This suggests that there is no direct top-down control
      over the MMN-generating process.

PMID- 11447337
TI  - Markedly reduced chronic nociceptive response in mice lacking the PAC1 receptor.
AB  - The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has
      been proposed to have a role in nociception. Here we have used the formalin test,
      thermal laser stimulation and mechanical von Frey stimulation to investigate
      possible alteration of PAC1-/- mice nociceptive behaviour. Our finding, that PAC1
      /- mice have a substantial, 75% decrease in nociceptive response during the late
      phase, provides clear evidence that the specific PACAP-receptor PAC1 is involved
      in the mediation of nociceptive responses during chronic conditions such as
      inflammation. PAC1-/- mice had small or no changes in the response to mechanical
      and thermal laser stimulation. This suggests a limited, if any, involvement of
      PAC1 in nociception after short-lasting stimuli. Injury-induced changes in DRG
      neuropeptide expression were more pronounced in PAC1-/- mice, implying
      neuroregulatory functions of PAC1.

PMID- 11447338
TI  - Two types of movement-related cortical potentials preceding wrist extension in
      humans.
AB  - We compared the occurrence patterns of movement-related cortical potentials
      (MRCPs) preceding wrist extension in athletes (kendoists and gymnasts) and non
      athletes. The MRCPs of the non-athletes started approximately 1.5 s before the
      EMG onset of wrist extension. In the athletes, the duration of the MRCPs was
      shorter and the amplitudes of early component (Bereitschaftspotential) were
      smaller than in the non-athletes. The MRCPs in the athletes started approximately
      400 ms before the onset of wrist extension and increased rapidly. In
      topographical maps, MRCPs of the athletes were localized markedly on the
      contralateral motor area (C3) compared with the non-athletes. In the present
      study, the duration of MRCPs was classified into two types.

PMID- 11447339
TI  - Ideographic characters call for extra processing to correspond with phonemes.
AB  - Cortical areas used in the copying of Japanese ideographic characters and
      syllabic characters were studied using functional magnetic resonance imaging in
      healthy volunteers. Complexity of characters was controlled to illustrate
      differences resulting from character to sound conversion differences between the
      ideographic and syllabic characters. Statistical comparisons indicated extensive
      activation in the fusiform gyrus, posterior portions around the intraparietal
      sulcus and in the conjunction area of BA 6, 9 and 44 (which is assumed to be
      Exner's area) during the copying of ideographic characters. These findings
      suggested that indirectness between ideographic characters and their
      pronunciation demands extra processing such as semantic mediation and intensive
      grapheme processing in comparison with syllabic characters.

PMID- 11447340
TI  - Functional imaging of brain activity in conscious monkeys responding to sexually
      arousing cues.
AB  - Olfactory cues can elicit intense emotional responses. This study used fMRI in
      male common marmoset monkeys to identify brain areas associated with sexual
      arousal in response to odors of ovulating female monkeys. Under light anesthesia,
      monkeys were secured in a specially designed restrainer and positioned in a 9.4 T
      magnetic resonance spectrometer. When fully conscious, they were presented with
      the scents of both ovariectomized and ovulating monkeys. The sexually arousing
      odors of the ovulating monkeys enhanced signal intensity in the preoptic area and
      anterior hypothalamus compared to the odors of ovariectomized monkeys. These data
      corroborate previous findings in monkeys based on invasive electrical lesion and
      stimulation techniques and demonstrate the feasibility of using non-invasive
      functional imaging on fully conscious common marmosets to study cue-elicited
      emotional responses.

PMID- 11447341
TI  - Regulation of glial differentiation of MHP36 neural multipotent cell line.
AB  - MHP36 is a nestin bFGF-dependent cell line isolated from embryonic hippocampus
      using a thermolabile form of SV40 T antigen. When grafted in ischemic hippocampus
      MHP36 cells differentiate and alleviate the cognitive deficit associated with the
      lesion. We report here in vitro features of MHP36 cells. First, we found that T
      Ag expression was not necessary for MHP36 growth as cells cultured at the
      nonpermissive temperature carry on proliferating at a normal rate, Second, we
      observed that part of MHP36 cells spontaneously differentiate into astrocytes
      when bFGF is removed at39 degrees C. This differentiation was increased 4-fold by
      leukemia inhibitory factor. Third, we found that the majority of cells
      spontaneously expressed oligodendrocytic markers (CNPase, A2B5, GalC) when
      cultured at low density.

PMID- 11447342
TI  - Baclofen antagonises intravenous self-administration of gamma-hydroxybutyric acid
      in mice.
AB  - gamma-Hydroxybutyric acid (GHB) is a widely used recreational drug known to exert
      positive reinforcing effects in animals and humans. The GABA(B) receptor agonist
      baclofen has been proved to possess antimotivational effect and to inhibit
      alcohol, cocaine, heroin and nicotine intake. In the present study we evaluated
      the effect of baclofen on i.v. self-administration of GHB in drug-naive mice
      under a fixed-ratio (FR-1) schedule of reinforcement and nose-poking-like
      response as operandum. Results show that baclofen was able to completely prevent
      GHB seeking behaviour, decreasing the rate of responding to basal values, without
      showing any reinforcing properties when made contingent on nose-poking response.
      Our findings demonstrate that baclofen antagonises GHB i.v. self-administration,
      supporting an important role for the GABA(B) receptor in reward-related
      mechanisms underlying addictive behaviour.

PMID- 11447343
TI  - Is the postganglionic sympathetic neuron zinc-enriched? A stop-flow nerve crush
      study on rat sciatic nerve.
AB  - Axonal transport of endogenous zinc ions in the rat sciatic nerve was studied by
      a stop-flow/nerve crush technique combined with zinc selenide autometallography
      (ZnSeAMG) at light and electron microscopic levels. Distinct accumulations of
      ZnSeAMG grains were detected, in particular proximal but also distal to the
      crushes, 1.5 h after the operation, and the amounts of zinc ions increased
      further in the following 3-8 h. Ultrastructurally, ZnSeAMG grains were located
      predominantly in unmyelinated axons. The data suggest that a subpopulation of
      sciatic nerve axons contains and transports zinc ions both antero- and
      retrogradely, indicating that the second neuron in the sympathetic nervous system
      is zinc enriched (ZEN).

PMID- 11447344
TI  - Abnormal brain white matter in schizophrenia: a diffusion tensor imaging study.
AB  - Fractional anisotropy and the mean diffusion coefficient were measured in the
      cerebral volume in 20 schizophrenic and 24 healthy subjects, men and women, using
      diffusion tensor imaging. In addition, 3D SPGR was used for segmentation of brain
      tissue into grey and white matter and cerebrospinal fluid. In schizophrenic
      patients, fractional anisotropy was reduced in the splenium of the corpus
      callosum and in adjacent occipital white matter. The segmentation revealed no
      tissue deficits in the volume of reduced fractional anisotropy. The mean
      diffusion was increased in the total white and grey matter volume of the
      schizophrenic patients compared with the healthy subjects. The findings support
      the view that global and regional white matter abnormalities occur in chronic
      schizophrenia.

PMID- 11447345
TI  - Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve
      terminals (synaptosomes) by suppression of voltage-activated calcium channel
      activity.
AB  - Lamotrigine (LAG) is an antiepileptic drug which is believed to suppress seizures
      by inhibiting the release of excitatory neurotransmitters. The present study was
      aimed at investigating the effect of LAG on the 4-aminopyridine (4AP)-evoked
      glutamate release in cerebrocortical nerve terminals (synaptosomes). LAG
      inhibited the release of glutamate evoked by 4AP in a concentration-dependent
      manner. This inhibitory effect was associated with a reduction in the
      depolarization-evoked increase in the cytoplasmic free Ca2+ concentration
      ([Ca2+]C). In addition, LAG did not alter the resting synaptosomal membrane
      potential or 4AP-evoked depolarization. Furthermore, ionomycin-evoked glutamate
      release was not affected by LAG. Based on these results, we suggest that
      presynaptic calcium influx blockade and inhibition of glutamate release may
      underlie the mechanism of action of LAG. These action may also contribute to
      their neuroprotective properties in excitotoxic injury.

PMID- 11447346
TI  - Stereopsis-processing regions in the human parieto-occipital cortex.
AB  - We performed fMRI on the human parieto-occipital cortex in order to identify the
      neural processing regions of stereopsis. Visual stimulation for stereopsis was
      performed with a random-dot stereogram displayed in the image guides of a new
      binocular visual stimulation device that we developed. Interestingly, regions
      from the dorsal portion of the occipital lobe to the superior parietal lobule
      were activated by binocular disparity, while the inferior parietal lobule was not
      activated. Moreover, these regions were shown as dominant in the right
      hemisphere. Functional brain mapping revealed that the processing regions of
      stereopsis were dorsally located in parieto-occipital cortex, and that the
      superior parietal lobule is an important region for neural processing of human
      stereopsis.

PMID- 11447347
TI  - Perinatal hypoxia-/ischemia-induced endothelin-1 mRNA in astrocyte-like and
      endothelial cells.
AB  - Under pathological conditions in the adult CNS, such as ischemia, subarachnoid
      hemorrhage and Alzheimer's disease, endothelin (ET)-1- and -3-like
      immunoreactivities are elevated in astrocytes of the injured adult brain.
      However, it is not clear whether this is due to increased synthesis or increased
      binding of ET-1. Further, it is not known whether ET-1 expression is altered in
      the perinatal brain after cerebral hypoxia/ischemia (H/I). Here, we determined
      the sites of ET-1 expression in perinatal mouse brain after H/I injury by in situ
      hybridization using a probe specific for the ET-1 gene. Astrocyte-like cells,
      which do not normally express ET-1 mRNA, showed high levels of ET-1 mRNA
      expression. Endothelial cells of the capillaries and small vessels also showed an
      increased level of ET-1 mRNA. Our data suggest that ET-1 mRNA levels in the
      astrocyte-like cells and vascular endothelial cells are dynamically regulated by
      ischemia and may participate in perinatal ischemia-related neural damage.

PMID- 11447348
TI  - Involvement of ERK and p38 MAP kinase in oxidative stress-induced phospholipase D
      activation in PC12 cells.
AB  - Exposure to hydrogen peroxide induced considerable activation of phospholipase D
      (PLD) in rat pheochromocytoma PC12 cells. This PLD activation was potentiated by
      orthovanadate and okadaic acid, suggesting that tyrosine kinase and
      serine/threonine kinase are involved. Furthermore, H2O2-induced PLD activation
      was partially inhibited by either MEK1 inhibitor (PD98059) or p38 MAP kinase
      inhibitor (SB203580), but a combination of both inhibitors resulted in nearly 80%
      suppression. The major isozyme was found to be PLD2 in PC12 cells by Western
      blotting analysis. When the PLD2-transfected COS-7 cells were exposed to H2O2,
      the PLD activation was markedly inhibited by the combined pretreatment with
      PD98059 and SB203580. To our knowledge, this study is the first demonstration
      that both ERK1/2 and p38 MAP kinase are involved in the PLD2 activation in PC12
      cells exposed to H2O2.

PMID- 11447349
TI  - Dynamics of frontal EEG activity, sleepiness and body temperature under high and
      low sleep pressure.
AB  - The impact of sleep deprivation (high sleep pressure) vs sleep satiation (low
      sleep pressure) on waking EEG dynamics, subjective sleepiness and core body
      temperature (CBT) was investigated in 10 young volunteers in a 40 h controlled
      constant posture protocol. The differential sleep pressure induced frequency
      specific changes in the waking EEG from 1-7 Hz and 21-25 Hz. Frontal low EEG
      activity (FLA, 1-7 Hz) during sleep deprivation exhibited a prominent increase as
      time awake progressed, which could be significantly attenuated by sleep satiation
      attained with intermittent naps. Subjective sleepiness exhibited a prominent
      circadian regulation during sleep satiation, with virtually no homeostatic
      modulation. These extremely different sleep pressure conditions were not
      reflected in significant changes of the CBT rhythm. The data demonstrate that
      changes in FLA during wakefulness are to a large extent determined by the sleep
      wake dependent process with little circadian modulation, and reflect differential
      levels of sleep pressure in the awake subject.

PMID- 11447350
TI  - Basal forebrain stimulation changes cortical sensitivities to complex sound.
AB  - Experience affects how brains respond to sound. Here, we examined how the
      sensitivity and selectivity of auditory cortical neuronal responses were affected
      in adult rats by the repeated presentation of a complex sound that was paired
      with basal forebrain stimulation. The auditory cortical region that was
      responsive to complex sound was 2-5 five times greater in area in paired
      stimulation rats than in naive rats. Magnitudes of neuronal responses evoked by
      complex sounds were also greatly increased by associative pairing, as were the
      percentages of neurons that responded selectively to the specific spectrotemporal
      features that were paired with stimulation. These findings demonstrate that
      feature selectivity within the auditory cortex can be flexibly altered in adult
      mammals through appropriate intensive training.

PMID- 11447351
TI  - Subjective contour illusion: sex-related effect of unilateral brain damage.
AB  - The aim of the study was to investigate the effect of unilateral brain lesions on
      the perception of subjective contours. Brain damage resulted in a reduced ability
      to perceive the illusion. The effect, however, was hemisphere and sex dependent.
      In women an illusion decrement due to either the left or right hemisphere damage
      was observed, while in men only right hemisphere damage caused a decrement. No
      specific effect of intrahemispheric localisation of lesion was found. We conclude
      that mechanisms contributing to subjective contour perception are right
      hemisphere dependent in males whereas in females they are bilaterally
      represented.

PMID- 11447352
TI  - Direction selectivity of excitatory and inhibitory neurons in ferret visual
      cortex.
AB  - Direction selectivity is a characteristic feature of neurons in the visual cortex
      of higher mammals. Excitatory and inhibitory cortical neurons receive different
      patterns of synaptic connections resulting in different receptive field
      properties. We have analyzed the direction tuning of excitatory and inhibitory
      neurons of ferret visual cortex using single unit recordings. Direction tuning
      was constant among neurons in a vertical column. The majority (> 80%) of
      excitatory (regular spiking) neurons were direction tuned or direction biased.
      Fast spiking (inhibitory) neurons were orientation, but only weakly or not
      direction tuned. This indicates that excitatory and inhibitory neurons have
      different functions in visual processing and their different integration in
      thalamocortical and intracortical circuits results in a diversification of
      receptive field properties.

PMID- 11447353
TI  - Development of peak performance in track cycling.
AB  - BACKGROUND: Retrospective analysis of peak performances can be a usefull tool for
      the estimation of future trends in high performance sports. The purpose of this
      study was to investigate the evolution of performance in track cycling from 1979
      to 1999 and to asses age- and gender-related differences. METHODS: We studied the
      results of the world track cycling championships for this period in 200 m, 1000
      m, individual and team pursuit races for elite and junior athletes. Overall
      trends, performance differences between rank 1 and 5, gender- and age-related
      differences were calculated. RESULTS: They show a significant (p<0.01)
      improvement in 1000 m, individual and team pursuit times for men and individual
      pursuit times for women. No significant evolution was seen in 200 m performance.
      In junior riders, only male athletes showed a continuous, significant improvement
      of average race speed in individual and team pursuit over the study period.
      Gender difference was 11+/-1.8% in all disciplines at all ages. Difference
      between elite and junior riders ranged between 5+/-2.1% for male and 6.1+/-2.2%
      for female athletes. The gap between rank 1 and 5 remained constant (2-3%) over
      the study period. CONCLUSIONS: A continuous improvement of performance over the
      last 20 years is visible in track cycling endurance disciplines. New technical
      developments show no statistical significant impact. The performance gap between
      male and female athletes is constant, independent of discipline or race distance
      and comparable to observations in other sports. Age-related differences in
      performance is most visible in disciplines requiring short, high intensity power
      output. Based on these data, estimation of possible winning times and adaptation
      of training programs for future track cycling competitions might be facilitated.

PMID- 11447354
TI  - Duration and seriousness of running mechanics alterations after maximal cycling
      in triathletes. Influence of the performance level.
AB  - BACKGROUND: Non-experienced triathletes use to complain about the difficulty to
      run after cycling. We tested the hypothesis that elite triathletes have lower
      and/or shorter alterations in running mechanics following a maximal cycling
      exercise than their less efficient counterparts. METHODS: The mechanical
      alterations in running after exhaustive cycling exercise were studied in eight
      elite (E) and 18 middle-level (M) triathletes. Before and after maximal cycling
      exercise, the subjects completed two 7-min runs on a treadmill at a velocity
      corresponding to that sustained during a triathlon. External mechanical cost was
      quantified during the first and last minute of each run from displacements of the
      centre of mass using a kinematic arm. RESULTS: The effect of cycling on the
      potential, kinetic and mechanical costs (respectively, 7.1+/-6.0% and 0.4+/-6.9%
      increase for M and E) during the first minute of running appeared to be more
      adverse (p<0.05) for M than E. The mechanical changes between pre- and
      postcycling exercise were similar among the two groups at the 6th minute,
      suggesting that the mechanical alterations due to a cycling fatigue in M are
      brief. CONCLUSIONS: Since the needs to run efficiently immediately after cycling
      are associated with performance in triathlon, the results of the present study
      have practical implications for training.

PMID- 11447355
TI  - Effects of regular and slow speed resistance training on muscle strength.
AB  - BACKGROUND: The study assessed a way to increase the intensity and effectiveness
      of resistance training by comparing training with a slower repetition speed to
      training with a conventional repetition speed. Slower repetition speed may
      effectively increase intensity throughout the lifting phase while decreasing
      momentum. METHODS: Two studies were done with untrained men (N=65) and women
      (N=82), (mean age=53.6) who trained two to three times per week for eight to 10
      weeks on a 13 exercise Nautilus circuit performing one set of each exercise.
      Participants exclusively trained using regular speed repetitions for 8 to 12
      repetitions per set at 7 sec each (2 sec lifting, 1 sec pause, 4 sec lowering) or
      a Super Slow training protocol where they completed 4 to 6 repetitions per set at
      14 sec each (10 sec lifting, 4 sec lowering). All of the participants were tested
      for either the 10 repetition-maximum (RM) weightload (regular-speed group) or the
      5-RM weightload (slow-speed group). RESULTS: In both studies, Super-Slow training
      resulted in about a 50% greater increase (p<0.001) in strength for both men and
      women than regular speed training. In Study 1, the Super-Slow training group
      showed a mean increase of 12.0 kg and the regular speed group showed an increase
      of 8.0 kg increase (p<0.001). In Study 2, the Super-Slow training group showed a
      10.9 kg increase and the regular speed group showed an increase of 7.1 kg
      (p<0.001). CONCLUSIONS: Super-Slow training is an effective method for middle
      aged and older adults to increase strength. Although studies still need to be
      done with at-risk populations, repetition speed should be considered when
      prescribing resistance training.

PMID- 11447356
TI  - Effects of plyometric training on jumping performance in junior basketball
      players.
AB  - BACKGROUND: Although the plyometric training has proved its efficiency, it
      remains generally unknown whether a limited amount of plyometric training could
      improve movements in subjects who already demonstrate high level of performance.
      METHODS: Three different training regimens were performed in order to study
      effects of plyometric training on elite junior basketball players. While control
      group (CG) participated only in the regular midseason training activity, another
      two groups performed a limited amount of plyometric training employing drop jumps
      from the height of either 50 cm (EG-50) or 100 cm (EG-100). The height of the
      maximal vertical jump (CMJ), as well as the maximal voluntary force (F) and the
      rate of force development (RFD) of hip and knee extensors were tested prior to
      and after the training. RESULTS: An increase in CMJ (4.8 and 5.6 cm in EG-50 and
      EG-100, respectively), as well as in F of hip extensors and RFD of knee extensors
      was observed in both experimental groups, while no significant changes were
      recorded in CG. When the pretest scores were used as a covariate, both
      experimental groups demonstrated higher increase in CMJ and RFD of knee extensors
      then CG. However, no differences were observed between EG-50 and EG-100. The
      multiple correlation between four isometric parameters and CMJ revealed R2=0.29.
      CONCLUSIONS: A limited amount of plyometric training could improve jumping
      performance in elite junior basketball players and this improvement could be
      partly related with an increase in F of hip extensors and RFD of knee extensors.
      However, neither of the two initial heights of the applied drop jumps proved to
      be more effective.

PMID- 11447357
TI  - Relationship between the slow component of oxygen uptake and the potential
      reduction in maximal power output during constant-load exercise.
AB  - BACKGROUND: The purpose of the present study was to examine the relationship
      between the slow component of oxygen uptake (VO2) and muscle fiber fatigue.
      Maximal power output (MPO) was used as an index of muscle fiber fatigue. METHODS:
      Two constant exercises were carried out at exercise intensities of 40% and 80% of
      maximal oxygen uptake (VO2max). Each exercise was repeated three times, once for
      the measurement for VO2, and the other two times for MPO testing, at 3 and 6
      minutes after work output. RESULTS: Reproducibility of MPO at rest was assessed
      by correlation coefficient. Its value was 0.933. At 40% VO2max, MPO did not
      significantly decrease from the resting value. At 80% VO2max, MPO significantly
      decreased by 129+/-77 watts at 3 min and by 178+/-108 watts at 6 min. The VO2
      kinetic at 40% VO2 was well described by a monoexponential function with a time
      constant of 0.432 min. However, at 80% VO2max, a slow component of the form of a
      linear drift superimposed on a monoexponential function with an essentially equal
      time constant (0.469 min) was unambiguously detected. This slow component was
      significantly related to the decrease in MPO (r=0.567). CONCLUSIONS: The present
      results suggested that the fatigue of muscle fibers may be one of the factors
      that produce the slow component of VO2 during high intensity exercise.

PMID- 11447358
TI  - Marathon finishers and non-finishers characteristics. A preamble to success.
AB  - BACKGROUND: To investigate if the characteristics and training profiles of
      runners are significant indicators to predict a successful completion of a
      marathon. METHODS:  EXPERIMENTAL DESIGN: comparative investigation between two
      groups of runners at a marathon race. SETTING: participants of the study came
      from the 1998 Standard Chartered New Airport International Marathon in Hong Kong.
      PARTICIPANTS: 113 runners were investigated, of which 58 runners dropped out at
      the first 10 km of the race, while the other 55 were those that consulted for
      physiotherapy service after the marathon. MEASURES: using questionnaire, the
      characteristics and the training profiles of these runners were obtained. These
      included weekly training distance, longest and shortest training distance per
      session in one week; warm-up and stretching exercise with the training sessions,
      number of marathons previously finished and the runners' opinion of optimal
      training mileage to complete a marathon. RESULTS: Independent t-tests with
      Bonferroni adjustment were used to investigate the difference between the two
      groups, the results showed significant difference in the weekly training distance
      (p=0.00), longest and shortest training distance per week (p=0.00), and personal
      opinion on optimal weekly training distance for a marathon (p=0.00). Logistic
      regression modeling was then employed to determine variables that best predict
      the likelihood of completing a marathon. CONCLUSIONS: The findings indicate that
      the non-finishers are poorly prepared and the results also identify that the
      longest mileage covered per training session is the best predictor for a
      successful completion of a marathon with an odds of 1.21.

PMID- 11447359
TI  - VO2max, ventilatory and anaerobic thresholds in rhythmic gymnasts and young
      female dancers.
AB  - BACKGROUND: This study examines the fitness level of a rhythmic gymnasts group
      and a young female classical dancers group. METHODS: Aerobic power (VO2max),
      individual ventilatory (IVT) and anaerobic thresholds (IAT) were assessed in 12
      elite rhythmic gymnasts, eight elite ballet dancers and 12 sedentary female
      subjects in the same age range (13-16 yrs). The VO2max, IVT and IAT were assessed
      during a continuous incremental running treadmill test. RESULTS: At IVT and IAT
      the VO2max expressed in ml x kg(-1) x min(-1) was significantly different between
      the three groups of subjects. The highest values were found in gymnasts (30.8+/
      2.6 for IVT and 43.8+/-3.5 for IAT) followed by the values of dancers (21.7+/-2.8
      for IVT and 30.5+/-3.1 for IAT) and controls (15.6+/-2.0 for IVT and 20.6+/-1.7
      for IAT). When the VO2max was expressed in percent of VO2max, the values at IAT
      were significantly different between all groups (gymnasts: 84.9+/-0.7; dancers:
      64.0+/-4.1; controls: 59.7+/-2.4) while at IVT no difference was found between
      dancers and controls (45.6+/-4.1 and 45.2+/-16, respectively). At maximal effort
      VO2 was significantly higher both in gymnasts and dancers (51.7+/-4.4 and 47.5+/
      3.0 ml x kg(-1) x min(-1), respectively), than in controls (34.5+/-2.5 ml x kg(
      1) x min(-1)). CONCLUSIONS: Although VO2max was similar between gymnasts and
      dancers, VO2 values at NT and IAT were able to discriminate the higher level of
      fitness in gymnasts with respect to dancers.

PMID- 11447360
TI  - Mechanomyography, electromyography, heart rate, and ratings of perceived exertion
      during incremental cycle ergometry.
AB  - BACKGROUND: The purpose of this investigation was to examine the relationships of
      mchanomyography (MMG), electromyography (EMG), heart rate (HR), and ratings of
      perceived exertion (RPE) versus power output during incremental cycle ergometry.
      METHODS: Nine adult males [mean (+/-SD) age 23 (+/-3) years] volunteered to
      perform an incremental test to exhaustion on a cycle ergometer. The MMG, EMG, HR,
      and RPE values were recorded at the end of each power output. RESULTS: The
      normalized (expressed as a percentage of maximal values) relationships for MMG,
      HR, and RPE versus power output were linear, while the EMG versus power output
      relationship was quadratic. Furthermore, there were no significant (p > 0.10)
      differences between slope coefficients for the relationships among MMG, HR, and
      RPE versus power output. CONCLUSIONS: The results of this investigation indicated
      that there were close associations among the mechanical (MMG), cardiac (HR), and
      perception of effort (RPE) aspects of cycle ergometry. In addition, there was a
      dissociation between the linear MMG pattern and quadratic EMG pattern with
      increasing power outputs.

PMID- 11447361
TI  - Effect of nostril dilatation on prolonged all-out intermittent exercise
      performance.
AB  - BACKGROUND: This study was designed to examine whether nostril dilatation would
      affect the ventilatory muscle (VM) function and the mean power output (PO) during
      prolonged all-out intermittent exercise. METHODS: Eight untrained young male
      subjects each completed 30 bouts of all-out exercise 20-sec each on a cycle
      ergometer interspersed with 40-sec recovery periods under (i) normal breathing
      and (ii) nostril dilatation conditions. For nostril dilatation, external nasal
      dilator (END) was used. Pre-exercise peak nasal inspiratory flow (PNIF), pre- and
      postexercise maximum inspiratory (MIP) and expiratory pressures were assessed in
      all trials. During exercise, ratings of perceived magnitude of breathing effort
      (RPMBE) and exertion (RPE) were recorded at 5-min intervals while ventilation,
      tidal volume, breathing frequency and oxygen consumption (VO2) were measured at
      20-sec intervals. RESULTS: Inspiratory muscle fatigue occurred during control
      trial as MIP reduced from 155.1+/-25.3 cm H2O to 140.5+/-31.2 cm H2O after the
      exercise. Pre-exercise PNIF was increased with END from 3.1+/-0.8 l x sec(-1) to
      3.8+/-1.0 l x sec(-1) showing that the nasal airflow resistance was reduced.
      Using END during exercise eliminated inspiratory muscle fatigue (no change in
      post-exercise MIP), and resulted in low average RPMBE and RPE, and high PO in
      comparison with the control values. In addition, the augmentation of PO was
      concomitant with no change in the average values of the VO2 and the ventilatory
      parameters. CONCLUSIONS: Exercise-induced VM fatigue occurs during the prolonged
      all-out intermittent exercise. Nostril dilatation with END during the exercise
      results in eliminating the VM fatigue and improving the PO.

PMID- 11447362
TI  - Effects of strength exercise and training on the natural killer cell counts in
      elderly humans.
AB  - BACKGROUND: To investigate the effects of strength exercise and training on the
      natural killer cell counts in elderly humans. METHODS: The study examined
      strength exercise-induced changes in the number of NK cells and changes in stress
      hormones in 16 sedentary elderly subjects before and after a 8-week strength
      training intervention. Blood samples were obtained before, immediately and 6
      hours after a standardized strength test. Blood samples were also obtained from
      ten sedentary young subjects, under the same conditions and from ten resting
      elderly subjects serving as time controls. RESULTS: Prior to training, older
      adults immediately decreased (from 165.4+/-19.5 microL to 110.6+/-14.3 microL;
      mean+/-SEM) their NK cell count in response to the standardized strength test,
      whereas young controls increased their count (from 157.6+/-28.8 microL(-1) to
      241.4+/-39.8 microL(-1)). After strength training, the same old subjects slightly
      increased (from 159+/-19.8 microL(-1) to 166.6+/-19.7 microL(-1)) their NK cell
      counts in response to the standardized strength test. In elderly subjects, no
      increase in stress hormone was observed following the strength test either before
      or after the strength training programme. CONCLUSIONS: The results suggest that
      in sedentary older adults, unlike young subjects, strength exercises can induce a
      transient decrease in NK cell count which can be cancelled by a short-term
      strength conditioning. Therefore, caution should be taken regarding
      immunocompetence of older adults when initiating a rehabilitation programme based
      on strength.

PMID- 11447363
TI  - Glucose tolerance during moderate prolonged exercise in women with oral
      contraceptives as compared to non-users.
AB  - BACKGROUND: The purpose of this study was to assess gluco-se tolerance during
      exercise in women on oral contraceptives. METHODS: To this end, we investigated
      the effects of glucose ingestion on glucose and hormonal responses in 7 women on
      oral contraceptives (OC(+); 21.3+/-1.3 yrs) and 7 normally menstruating (OC(-);
      22.6+/-1.3 yrs) during an ergocycle test (30 min, 60% VO2max). Venous blood
      samples were withdrawn at 0, 3, 5, 10, 15 and 30 min exercise and at the 30th min
      postexercise. Glucose was ingested per os (0.5 g x kg(-1) b.w) between the 2nd
      and the 3rd min of the exercise. RESULTS: Under resting condition, plasma glucose
      and catecholamine concentrations were similar in both groups whereas plasma GH
      and insulin levels were greater in OC(+) (p<0.05). Glucose/insulin ratio (G/I),
      used as an indicator of insulin resistance, suggested a reduced insulin
      sensitivity at rest in the OC(+) (p<0.05). No significant differences were
      observed between OC(+) and OC(-) in plasma glucose, insulin, and catecholamine
      concentrations during exercise. Plasma GH values were greater in OC(+) from the
      15th min of the exercise and during the recovery period (p<0.01). CONCLUSIONS:
      This study indicated that oral glucose ingestion at the onset of prolonged
      submaximal exercise induced similar glucose tolerance in women taking or not oral
      contraceptives.

PMID- 11447364
TI  - Chronic medium-chain triacylglycerol consumption and endurance performance in
      trained runners.
AB  - BACKGROUND: This study was designed to assess the effects of chronic consumption
      of medium-chain triacylglycerols (MCT) on endurance running performance. METHODS:
      EXPERIMENTAL DESIGN: participants completed the study in a randomized, cross
      over, placebo-controlled, double-blind fashion. SETTING: participants were
      recruited from the general community to participate in this university based
      study. PARTICIPANTS: twelve trained male endurance runners (30.5+/-5.2 years of
      age) completed the study. INTERVENTIONS: participants consumed dietary
      supplements containing either 56 g of corn oil (LCT) or 60 g of MCT oil daily for
      2 weeks. Following each dietary phase, participants completed a maximal treadmill
      test followed by an endurance treadmill test in which participants ran at 85%
      VO2max for 30 min proceeded by 75% VO2max until exhaustion. MEASURES: blood was
      taken at rest and after 45 min of exercise to assess concentrations of lactate,
      glucose, beta-hydroxybutyrate (beta-HBA), free fatty acids (FFA), glycerol and
      triacylglycerols (TG). Performance was assessed as time to exhaustion. RESULTS:
      VO2max (72.0+/-8.0 vs 72.4+/- 9.0 ml x kg(-1) x min(-1)) and endurance time
      (99.8+/-23.5 vs 106.5+/-29.4 min) did not differ (p>0.05) between MCT and LCT
      trials, respectively. No differences (p>0.05) in lactate, glucose, beta-HBA, FFA,
      glycerol or TG were detected between trials. Respiratory exchange ratio (RER) was
      higher (p<0.05) at 15 min for the MCT trial (0.97+/-0.10) versus the LCT trial
      (0.90+/-0.20), but was similar between trials at other timepoints. CONCLUSIONS:
      Results indicate that chronic MCT consumption neither enhances endurance nor
      significantly alters performance-related metabolism in trained male runners.

PMID- 11447365
TI  - The effects of supplemental carbohydrate ingestion on intermittent isokinetic leg
      exercise.
AB  - BACKGROUND: The purpose of this investigation was to examine the effects of
      carbohydrate (CHO) supplementation on isokinetic leg extension/flexion exercise
      performance, blood glucose responses, blood free fatty acid (FFA) responses, and
      blood lactate (La) responses. METHODS: Eight resistance trained males (mean+/
      SEM, age: 23.7+/-1.3 yrs, height: 180.0+/-3.5 cm, bodymass: 94.9+/-4.9 kg)
      participated in a randomized, double blind protocol with testing sessions
      separated by 7-d. Subjects were given CHO or placebo (P) while performing 16 sets
      of 10 repetitions at 120 degrees x s(-1) on a Cybex isokinetic dynamometer.
      Performance variables measured were; total work (TW), average work (AW), peak
      torque (PT) and average torque (AT). Plasma glucose (PG), FFA, and La were
      measured prior to testing (PRE), after set 8 (MID), and 16 (POST). RESULTS:
      Results indicated that the CHO treatment elicited significantly (p<0.05) more TW
      (CHO: 41.1+/-3.9 kJ; P: 38.1+/-3.9 kJ) and AW (CHO: 2.6+/-0.2 kJ; P: 2.4+/-0.2
      kJ). There were no differences (p<0.05) between treatments for PT of the
      hamstrings (CHO: 91.6+/-6.5 Nm; P: 87.4+/-8.5 Nm) and quadriceps (CHO: 129.7+/
      9.5 Nm; P: 123.0+/-10.6 Nm). The AT of the hamstrings (CHO: 77.8+/-5.2 Nm; P:
      75.7+/-8.7 Nm) and quadriceps (CHO: 116.9+/-8.9 Nm; P: 110.0+/-8.5 Nm) were not
      statistically different (p>0.05) between the treatments. PG was significantly
      higher at the POST blood draw in the CHO treatment. No significant differences
      (p>0.05) were observed between the treatments for FFA and La concentrations.
      CONCLUSIONS: The data from this investigation indicate that the use of CHO
      supplementation during isokinetic leg exercise allows for the performance of more
      work.

PMID- 11447366
TI  - The effects of diet and supplements on a male world champion lightweight rower.
AB  - A world-class lightweight rower who came to the Hong Kong Sports Institute was
      evaluated over a two-month period of training. He was preparing for the 1995
      World Rowing Championships. The subjects trained for approximately 70 minutes per
      day at different levels of intensity, to simulate race conditions. Caloric
      expenditures (based upon heart rate response and estimation from specific
      activity) were estimated to be approximately 4125 kcal/day. A three day dietary
      survey revealed that the subject was able to maintain caloric balance (caloric
      intake = 4088 kcal/day). Body weight was maintained at a constant level, another
      indication that the subject was able to meet energy needs. A breakdown of his
      food intake revealed protein, carbohydrate, and fat, made up 19%, 51%, and 30% of
      his caloric intake, respectively. This was somewhat surprising since
      recommendations for endurance athletes are for higher carbohydrate contribution.
      During and after the training bouts the subject consumed two separate
      carbohydrate supplements. A total of 218 g of carbohydrate were consumed daily.
      This level of supplementation was able to maintain the subject's blood glucose
      concentration at normal levels following recovery from exercise. Comparisons of
      recovery heart rates when either water or carbohydrate was consumed indicate a
      beneficial effect of the supplement. Despite consuming carbohydrates at lower
      than recommended levels, this athlete went on to win this third gold medal in
      rowing.

PMID- 11447367
TI  - Relationship between isokinetic strength of the internal and external shoulder
      rotators and ball velocity in team handball.
AB  - BACKGROUND: The purpose of this study was to examine the relationship between the
      rotational strength of shoulder and ball velocity in team handball players from
      various levels. METHODS: Three groups of young healthy, male subjects took part
      in the experiments: one group of 15 handball players, the best of League A1
      scorers, another group of 12 handball players, the best of League A2 scorers and
      a random sample of 15 physical education students. Each subject was tested on a
      Cybex II isokinetic dynamometer. The concentric action of the internal and
      external rotation of the dominant shoulder was examined at 60, 180 and 300
      deg/sec. Ball velocity was examined in three types of throw: (a) on the spot, (b)
      with a cross-over step, and (c) with a vertical jump. Statistical analysis was
      performed using the Pearson product-moment correlation and one-way analysis of
      variance. RESULTS: The differences of peak torque values of the internal and
      external shoulder rotation between the three groups were not statistically
      significant. The differences between groups regarding ball velocity in all types
      of throw were statistically significant (p<0.001). The relationship between IR
      and ER rotation of the shoulder and ball velocity was not statistically
      significant, except the jump shot. CONCLUSIONS: The main finding of this study
      was that peak torque of IR and ER of the shoulder was not a good indicator of
      throwing velocity at any type of throw, except the jump shot, in all subjects,
      regardless of their throwing ability.

PMID- 11447368
TI  - Shoulder range of motion characteristics in collegiate baseball players.
AB  - BACKGROUND: To determine range of motion and capsular characteristics of dominant
      and nondominant shoulders in baseball players. Our hypothesis was that there is a
      significant difference between dominant and nondominant range of motion in
      collegiate baseball players with unoperated and without shoulder pain. METHODS: 
      DESIGN: prospective, range of motion measurements during regular season. SETTING:
      two collegiate baseball teams in Houston. PARTICIPANTS: 15 pitchers and 23
      position players. MAIN OUTCOME MEASURES: shoulder range of motion was evaluated
      by goniometric technique in all baseball players. Horizontal adduction (cross
      body reach test) and active internal rotation (reach behind back) in standing
      position and external rotation and internal rotation in supine lying position
      were measured for each player. RESULTS: Average external rotation with the arm in
      90 degrees of abduction was significantly greater and average internal rotation
      was less in the dominant shoulder than in the nondominant shoulders, both in
      pitchers and position players. There was no statistical difference in shoulder
      horizontal adduction. Both dominant and nondominant shoulders of pitchers had
      greater average range of motion in horizontal adduction and external rotation at
      90 degrees of abduction and less average internal rotation than those of position
      players. Although there was a significant difference in active internal rotation
      as cm between dominant and nondominant shoulders both in both groups, no
      difference was found between pitchers and position players. CONCLUSIONS:
      Differences in the range of motion in the throwing shoulder of baseball players
      exist involved in overhead throwing motions and should be considered in
      rehabilitation of the upper extremity after injury and in the prevention of
      injury for pitchers and position players.

PMID- 11447369
TI  - Calcaneal bone mineral and ultrasound attenuation in male athletes exposed to
      weight-bearing and nonweight-bearing activity. A cross-sectional report.
AB  - BACKGROUND: To determine if the expected differences in bone mineral
      content/density of the calcaneus among male athletic groups that undertake weight
      bearing and nonweight-bearing activity are also apparent for bone quality as
      assessed by quantitative ultrasound (QUS) attenuation. METHODS:  EXPERIMENTAL
      DESIGN: cross-sectional. SETTING: a University research laboratory. PARTICIPANTS:
      we studied 30 young men: 10 Finnish national level jumpers whose training
      incorporates repeated impacts to the heel, 10 aquatics athletes whose skeletons
      are exposed to nonweight-bearing activity, and 10 sedentary men matched for age
      and body weight. MEASURES: bone mineral content (BMC, g x cm(-1)), areal bone
      mineral density (BMDa; g x cm(-2)) and presumed volumetric BMD (BMDv, g x cm(-3))
      was measured by single energy photon absorption (SPA). Broadband ultrasound
      attenuation (BUA using Fourier spectral estimation and UBI-4 using Burg spectral
      estimation, both in db/MHz) was assessed by a new QUS device (QUS-1TM, Metra
      Biosystems). RESULTS: There was no difference in years of sport specific training
      or total training time per week between athlete groups. BMC, BMDa and BMDv were
      significantly different among groups (p=0.0001) with jumpers being higher than
      aquatics athletes and controls. BMC of jumpers was 52% and 39% higher than
      controls and aquatics athletes, respectively, while the corresponding values for
      BMDv were 34% and 28%. However, BUA values were not significantly different
      (p=0.10) among groups nor was UBI-4 (p=0.03; jumpers values were 7% and 6% higher
      than aquatics athletes and controls, respectively). CONCLUSIONS: These cross
      sectional results indicate that bone mineral content and density of the calcaneus
      are substantially higher in jumpers than individuals engaged in nonweight-bearing
      or regular weight-bearing activity. However, parameters assessed by QUS
      attenuation are not markedly different, which suggests that bone quality
      properties may not be as responsive as that of bone mineral content/density to
      habitual skeletal loading.

PMID- 11447370
TI  - Croatian rugby project-Part I. Anthropometric characteristics, body composition
      and constitution.
AB  - BACKGROUND: There are no data in important literature about the anthropometric
      characteristics of rugby players in countries where rugby is not a popular sport.
      The goals of this study were to analyze morphological anthropometric
      characteristics, body composition and constitution of players in the first
      Croatian-Slovenian rugby league (CSRL) with regard to player's position in the
      team, team position in the division, and to compare results with the results of
      rugby players from the more popular rugby leagues. METHODS: The study was carried
      out in a sample of voluntarily included 111 male rugby players from six clubs
      members of the CSRL, in the season 1996/97. Eleven anthropometric measures
      required for the calculations of body mass index (BMI), body fat percentage
      (BF%), and somatotype components were obtained in the clubs according to the
      recommendations by Jackson and Pollock and Heath and Carter. RESULTS: Forwards in
      the CSRL are on the average 93.5 kg heavy, 182.4 cm tall, with BMI 28.3 kg/m2,
      BF% 20.8% and somatotype 6.7-5.9-1.4. Backs are on average 82.2 kg heavy, 178.3
      cm tall, with BMI 26.1 kg/m2, BF% 16.9% and somatotype 5.3-5.3-1.5. Backs from
      upper half of the division are on the average heavier than those from lower half,
      BF% in forwards from upper half of the division is higher than in forwards from
      lower half. Both differences were found to be statistically significant (p<0.05).
      CONCLUSIONS: Compared with the rugby players from more developed rugby leagues,
      forwards from the CSRL are lighter, backs are heavier and both have higher body
      fat percentage. Backs and forwards are more endomorphic and forwards are less
      mesomorphic compared with the rugby players from more developed rugby leagues.

PMID- 11447371
TI  - Somatotype, role and performance in elite volleyball players.
AB  - BACKGROUND: The purpose of the present study was to examine the importance of the
      somatometric components of elite male and female volleyball players in relation
      to their different game roles and levels of performance. METHODS: Two hundred and
      thirty-four male athletes (aged 24.7+/-4.4 years) and 244 female athletes (aged
      23.1+/-4.4 years) from the Italian A1 and A2 volleyball leagues underwent
      anthropometric measurements during the 1992-1993 and 1993-1994 seasons.
      Somatotypes were estimated with the Heath-Carter method. RESULTS: Marked sexual
      dimorphism in somatotype was observed in the total sample. The average somatotype
      for men was 2.2-4.2-3.2 (SD 0.7-0.9-0.9), and for women it was 3.0-3.3-2.9 (SD
      0.8-1.0-0.9). The somatotype was significantly different in players at different
      levels of performance (A1 vs A2 leagues), as it follows: 2.1-4.1-3.3 (SD 0.6-0.8
      0.7) vs 2.3-4.3-3.0 (SD 0.7-1.0-0.8) in males; 2.9-3.1-3.0 (SD 0.8-1.0-0.9) vs
      3.1-3.5-2.7 (SD 0.8-0.9-0.8) in females. The somatotype was also significantly
      different in players in different roles. In male sex the mean somatotypes for
      setters were 2.4-4.5-2.8 (SD 0.7-0.9-0.8), for centres they were 2.0-4.0-3.5 (SD
      0.6-1.0-0.8), for spikers they were 2.2-4.3-3.0 (SD 0.6-0.9-0.7), for opposites
      they were 2.2-4.3-3.1 (SD 0.6-0.9-0.8). In female sex the mean somatotypes for
      setters were 3.1-3.6-2.5 (SD 0.8-1.0-1.0), for centres they were 2.8-3.1-3.1 (SD
      0.8-0.9-0.7), for spikers they were 3.0-3.5-2.8 (SD 0.9-1.0-0.9) and for
      opposites they were 3.0-3.2-3.0 (SD 0.7-0.9-0.8). CONCLUSIONS: The physique of
      athletes in the A1 league is characterized by higher ectomorphy and lower
      endomorphy and mesomorphy. There is also a slight tendency of male players to a
      greater homogeneity in somatotype within the group at the maximum level of
      performance. Moreover somatotype differs in relation to game role in volleyball
      players of both sexes: the mesomorphic component is maximal in setters, while the
      ectomorphic component is maximal in centres.

PMID- 11447372
TI  - Psychophysiological stress in judo athletes during competitions.
AB  - BACKGROUND: The relationships between psychophysiological variables were
      investigated by comparing physiological responses (salivary cortisol and
      testosterone concentrations) and psychological responses (measured by the
      Competitive State Anxiety Inventory-2 -CSAI-2-and by the State-Trait Anxiety
      Inventory -STAY-) prior to judo competitions at two levels (regional versus
      interregional). METHODS: Twelve male judo competitors at interregional level
      (mean age 22.2+/-1.6 years) entered the experimentation after informed consent.
      Judo athletes completed the CSAI-2 prior to both competitions and collected
      saliva for cortisol and testosterone analysis on three occasions: during a
      resting day (baseline values) and prior to and after both competitions. Trait
      scales of the STAI (Y-2) were used during a resting baseline period with no
      stressful situations in order to measure participant's self reported anxiety.
      RESULTS: Cognitive and somatic anxiety were higher in interregional championships
      compared to regional championships whereas self-confidence was significantly
      lower. Cortisol levels increased sharply (about 2.5 fold resting levels)
      throughout both competitions with no changes in testosterone levels. Positive
      relationships between anxiety components (somatic and cognitive anxiety) and
      cortisol were noted in both competitions. CONCLUSIONS: Salivary cortisol,
      together with anxiety components, may provide a better sensitive index of
      physiological stress than testosterone concentrations.

PMID- 11447373
TI  - Urine catecholamine concentrations and psychophysical stress in elite tennis
      under practice and tournament conditions.
AB  - BACKGROUND: The purpose of the study was to specify and define the differences of
      psychophysical stress in elite tennis players under practice and tournament
      conditions. METHODS: Basal, pre- and postcompetition urine samples of 26
      nationally ranked players (NR) were analysed for concentrations of epinephrine
      (EPI) and norepinephrine (NE) under practice (P) and tournament conditions (T).
      Results were completed by the values obtained from two internationally ranked
      players (IR) competing in 6 (player A) and 5 (player B) Davis-Cup matches,
      respectively. RESULTS: In NR, pre- and postcompetition concentrations for EPI
      were significantly higher under tournament conditions (T: 1.33+/-0.65 and 3.66+/
      2.51 microg/100 mg creatinine vs P: 0.61+/-0.39 and 0.97+/-0.59 microg/100 mg
      creatinine). The NE/EPI ratio showed significantly inverse results (T: 3.53+/
      1.87 and 3.58+/-1.59 vs P: 8.08+/-6.99 and 10.03+/-6.58), whereas the
      concentration of NE did not differ between the two conditions. Significant
      correlations were found between the level of perceived nervousness (ten-point
      likert scale) and the postcompetition concentration of EPI (r=0.491, p<0.05) and
      the NE/EPI ratio (r=-0.595, p<0.01). Players who felt affected by nervousness in
      their performance outcome showed significantly lower NE/EPI ratios (2.73+/-1.44
      vs 4.49+/-2.54, p<0.05). The Davis-Cup-Players showed intra-individually constant
      but inter-individually different concentrations of EPI (A= 2.2+/-0.5 vs B= 7.0+/
      0.8 microg/100 mg creatinine), NE (A= 7.4+/-2.2 vs B= 15.5+/-3.2 microg/100 mg
      creatinine) and the ratio of NE/EPI (A= 3.7+/-2.2 vs B= 2.2+/-0.7). CONCLUSIONS:
      In tennis tournaments, sympathetic activity is increased due to a higher
      psychological stress which may impair performance. Practical efforts should focus
      on psycho-regulative methods and psychophysical regeneration for players dealing
      with a chronic sympathetic hyper-activation.

PMID- 11447374
TI  - Fortuitously discovered persistent left superior vena cava in young competitive
      athletes. Clinical implications of sports physicians.
AB  - This report describes two athletes with persistent left superior vena cava
      (PLSVC) accidentally identified during preparticipation medical evaluation. The
      clinical implications of PLSVC for sports physicians are also discussed. A 16
      year-old male ice hockey player and an 18-year-old male high-level field hockey
      player visited our institute for medical evaluation prior to participating in
      competition. Neither complained of palpitation, faintness or syncope, which would
      have suggested a possible cardiac rhythm disturbance, or had been informed of any
      abnormalities in previous physical examinations. Nonetheless, echocardiography
      revealed dilated coronary sinuses, and venography confirmed PLSVC and, in one
      case, showed the absence of the right superior vena cava. Electrocardiograms
      showed the field hockey player to have an ectopic atrial rhythm with left axis
      deviation of the frontal plane P-wave and the ice hockey player to have normal
      sinus rhythm. Symptom-limited treadmill testing revealed nothing abnormal, and
      after explaining the possible rhythm instability and the potential risk
      associated with cardiac surgery, the subjects were permitted full participation
      in competitive sports. Although information is scarce, available data on PLSVC
      suggest it is benign for competitive athletes. Nevertheless, complications
      arising from other cardiovascular anomalies, from potential cardiac rhythm
      disturbances, and from cardiac surgery necessitated by major injuries should be
      considered prior to participation in competitive sports.

PMID- 11447376
TI  - Alternative agents in asthma.
AB  - Glucocorticosteroids are the backbone of asthma therapy and are administered
      mainly by the inhaled route. Patients with "difficult" asthma are not a single
      homogeneous group. Some are stable on high-dose steroid therapy but experience
      unacceptable side effects; others remain unstable despite receiving high doses of
      inhaled or oral steroids. Several different steroid-sparing and alternative
      agents have been tried, with varying degrees of success. Some success has been
      achieved with conventional immunosuppressants such as methotrexate, gold, and
      cyclosporin A, but these agents can be justified only in a limited range of
      cases. Leukotriene receptor antagonists have proved a useful addition to asthma
      therapy and have been shown to have a modest steroid-sparing effect. Although the
      existing range of alternative agents has not proved to be particularly effective,
      several new therapeutic agents have been developed to target specific components
      of the inflammatory process in asthma. These include IgE antibodies, cytokines,
      chemokines, and vascular adhesion molecules. Future developments might include
      better forms of immunotherapy and strategies targeting the remodeling of
      structural elements of the airways.

PMID- 11447377
TI  - Genetics of airway hyperresponsiveness.
AB  - Asthma is a disease characterized by intermittent airway obstruction,
      inflammatory cell infiltrates, increased mucus production, lung epithelial
      remodeling, and airway hyperreactivity. The genetics of asthma, as investigated
      in animal models, is poorly understood. Because no animal model of asthma mimics
      all of the pathologic and physiological features of asthma, genetic studies have
      focused on several phenotypes, including intrinsic or native airway
      hyperreactivity. It is generally accepted that both genetic and environmental
      factors determine the phenotypic expression of this complex disease. The genetics
      of airway hyperresponsiveness, as investigated in the mouse, are presented in
      this review. The inbred mouse currently represents the most valuable genetic
      resource for understanding the factors that control this complex phenotype.

PMID- 11447378
TI  - Functional CD137 receptors are expressed by eosinophils from patients with IgE
      mediated allergic responses but not by eosinophils from patients with non-IgE
      mediated eosinophilic disorders.
AB  - BACKGROUND: CD137 (ILA/4-1BB), a member of the TNF/nerve growth factor receptor
      superfamily, has previously been suggested to be involved in T-cell activation
      and differentiation. OBJECTIVE: The aim of this study was to investigate
      expression and potential function of CD137 in eosinophils. METHODS: Eosinophils
      were isolated from normal control subjects as well as from patients with
      bronchial asthma, patients with atopic dermatitis, and patients with idiopathic
      eosinophilia. CD137 expression was analyzed by RT-PCR and flow cytometry. The in
      situ expression of CD137 on eosinophils in nasal polyp and skin tissues was
      analyzed through use of immunohistochemistry. To examine whether CD137 regulates
      eosinophil death and apoptosis, cells were stimulated with a plate-bound anti
      CD137 antibody in the presence or absence of survival cytokines. Cell death was
      measured by means of an ethidium bromide exclusion test. Apoptosis was determined
      by analyzing phosphatidylserine surface exposure. RESULTS: Blood and tissue
      eosinophils from patients with IgE-mediated allergic responses (atopic
      dermatitis, extrinsic asthma) express CD137. In contrast, eosinophils from normal
      control individuals and patients with non-IgE-mediated eosinophilic inflammatory
      responses (intrinsic asthma, idiopathic eosinophilia) express neither detectable
      levels of mRNA nor protein for CD137. Expression of CD137 in eosinophils was
      induced in vitro by stimulating the cells with supernatants derived from in vivo-
      or in vitro-activated T cells, suggesting that a soluble T cell-derived factor
      might be responsible for the observed phenomenon. Although CD137 expression was
      associated with increased IgE levels, IL-4 and IL-13 did not induce CD137 gene
      expression in eosinophils. Activation of CD137 abrogated both GM-CSF-mediated and
      IL-5-mediated antiapoptosis in CD137-expressing eosinophils but not in CD137
      deficient eosinophils. In contrast, the survival effect of IFN-gamma was not
      affected by anti-CD137 treatment. CONCLUSION: Our data indicate that CD137
      activation might limit GM-CSF-mediated and IL-5-mediated antiapoptosis of
      eosinophils. The absence of this potential anti-inflammatory mechanism might
      further increase eosinophil numbers at inflammatory sites in patients with
      intrinsic asthma and patients with idiopathic eosinophilia. The T cell-derived
      factor that induces CD137 expression in eosinophils remains to be identified.

PMID- 11447379
TI  - Effects of prednisone on the cellular responses and release of cytokines and
      mediators after segmental allergen challenge of asthmatic subjects.
AB  - BACKGROUND: Systemic glucocorticoids are a major therapy for the management of
      allergic inflammation and asthma; however, information about their effects in
      vivo are limited. OBJECTIVE: This study was performed to examine the effects of
      prednisone on inflammatory mediators, cytokines, and cellular responses in the
      model of segmental allergen challenge (SAC) of allergic asthmatic subjects.
      METHODS: The effects of a 3-day pretreatment with oral prednisone (30 mg twice
      daily) on the physiologic and inflammatory responses to SAC were studied in 10
      allergic asthmatic subjects in a double-blind, placebo-controlled, crossover
      protocol. RESULTS: Prednisone improved baseline FEV(1) by 10% and modestly
      inhibited the SAC-induced fall in FEV(1) at 30 minutes and at 6 to 8 hours. Five
      minutes after challenge, levels of histamine, PGD(2), 9alpha,11beta-PGF(2), and
      thromboxane B(2) increased in bronchoalveolar lavage fluid (median increase, 5-
      to 14-fold); prednisone did not inhibit these responses. Prednisone inhibited
      (median decrease, 66%-97%) the total influx of inflammatory cells, specifically
      eosinophils, basophils, and some subsets of T lymphocytes (CD4, CD45RA, and
      CD45RO cells) assessed 19 hours after SAC, but it did not inhibit the influx of
      neutrophils. Increases in soluble E-selectin, kinins, and albumin were also
      inhibited by the glucocorticoid (median decrease, 36%-74%). Prednisone treatment
      inhibited the appearance of mRNA, protein, or both for T(H)2 cytokines (IL-4 and
      IL-5), as well as for IL-2 and transforming growth factor alpha, but did not
      inhibit increases of immunoreactive GM-CSF in bronchoalveolar lavage fluid.
      CONCLUSION: These studies indicate that prednisone suppresses multiple components
      of allergic airway inflammation, including cell recruitment, adhesion molecule
      expression or release, airway permeability, and production of cytokines
      potentially involved in airway immunity or remodeling.

PMID- 11447380
TI  - Cost-effectiveness of inhaled corticosteroids in adults with mild-to-moderate
      asthma: results from the asthma policy model.
AB  - BACKGROUND: Inhaled corticosteroids remain underused among United States-based
      clinicians in treating mild-to-moderate adult asthma. OBJECTIVE: The purpose of
      this investigation was to estimate the clinical impact, health-related quality of
      life, cost, and cost-effectiveness of inhaled corticosteroid therapy in a
      population of patients aged 18 years and over with FEV(1) = 60% to 100% of
      predicted normal. METHODS: We performed a cost-effectiveness analysis of quick
      relievers (eg, short-acting beta-agonists) on an as-needed basis plus inhaled
      corticosteroid therapy versus quick relievers alone. A mathematical simulation
      model was developed to forecast symptoms, acute exacerbations, quality-adjusted
      life-years (QALYs), health care costs, and cost-effectiveness, measured in both
      dollars per QALY gained and dollars per symptom-free day gained. All evaluation
      outcomes were discounted at an annual rate of 3% and measured over a 10-year
      planning horizon. Data on the natural history of disease, drug efficacy, patient
      preferences, and economic costs were obtained from a variety of observational
      cohorts, randomized trials, and patient surveys. RESULTS: Over a 10-year period,
      use of inhaled corticosteroids increases total health costs from roughly $5,200
      to $8,400 and improves QALYs from 6.8 to 7.0, implying an incremental cost of
      $13,500 per QALY gained. Costs per symptom-free day gained are $7.50. Both per
      person acute exacerbations and hospitalizations are reduced by 33%. The cost
      effectiveness findings are sensitive to the assumed efficacy and side-effects of
      inhaled corticosteroid therapy. CONCLUSIONS: Inhaled corticosteroids appear to
      deliver good comparative value in adults with mild-to-moderate asthma. Although
      more research is needed to understand their impact on preferences regarding side
      effects and compliance, these findings might be useful for priority-setting in
      limited resource situations.

PMID- 11447381
TI  - Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive
      patients with asthma.
AB  - BACKGROUND: Patients with aspirin-sensitive respiratory disease experience cross
      reactions to all nonsteroidal anti-inflammatory drugs, which inhibit
      cyclooxygenase enzymes. With the introduction of antiarthritis drugs, which
      selectively inhibit cyclooxygenase-2, questions are raised as to whether cross
      reactivity occurs between aspirin and these new cyclooxygenase-2 inhibitors.
      OBJECTIVE: The goal of this study was to determine whether rofecoxib cross-reacts
      in aspirin-sensitive patients with asthma. METHODS: Sixty patients with asthma
      underwent doubleblinded, placebo-controlled oral challenges with rofecoxib (12.5
      mg, 25 mg, and 2 placebos) over 48 hours in our General Clinical Research Center.
      The next day, aspirin sensitivity was proven in each of the 60 patients through
      use of single-blinded oral aspirin challenges. RESULTS: None of the 60 patients
      experienced any symptoms, changes in nasal examination findings, or declines in
      FEV(1) values during their challenges with rofecoxib. All 60 patients experienced
      typical naso-ocular and asthmatic reactions to aspirin with a mean provoking dose
      of 61 mg. The exact 1-sided CI for the probability of rofecoxib inducing
      crossreactions in aspirin-sensitive patients with asthma is calculated to be
      between 0% and 0.05%. CONCLUSION: Given that none of the 60 patients reacted to
      rofecoxib and given the statistical power of this large sample size, we conclude
      that cross-reactivity between aspirin and rofecoxib does not occur in patients
      with aspirin-sensitive respiratory disease. This does not exclude rofecoxib from
      participating in other types of reactions, including immune recognition after
      prior treatment with the drug. From the standpoint of the mechanisms involved in
      aspirin-induced respiratory reactions, this study strongly supports inhibition of
      cyclooxygenase-1 as the essential initiator of these types of reactions.

PMID- 11447382
TI  - The role of symptomatic colds in asthma exacerbations: Influence of outdoor
      allergens and air pollutants.
AB  - BACKGROUND: Both air pollutants and respiratory viral infections have been
      recognized to be important triggers of asthma exacerbations, but the possible
      interaction of these has not been assessed in an epidemiologic study. OBJECTIVE:
      In this study, we aimed to assess the possible associations of symptomatic colds
      with outdoor allergens and air pollutants in exacerbating asthma. METHODS: A
      total of 57 adults and children with asthma participated in a 1-year study in
      Vancouver, British Columbia. Diary cards recording symptoms of asthma and colds,
      medication usage, and peak expiratory flow rates were completed twice daily.
      Outdoor air pollutant levels and levels of pollen and fungal spores were
      measured. Levels were examined for associations with exacerbations of asthma with
      symptoms of a cold, as compared with asthma exacerbations with no cold symptoms
      and colds in the absence of asthma exacerbations. RESULTS: Of 130 asthma
      exacerbations, 47% were associated with cold symptoms (accounting for 44% of
      episodes of colds). Asthma exacerbations with colds were associated with higher
      levels of sulfur dioxide, and nitric oxide during March to November in comparison
      with asthma exacerbations without cold symptoms (P <.018). Cold-symptom days
      overall were more common in winter and were significantly associated with lower
      temperatures, lower ozone levels, and higher sulfur dioxide, nitrogen dioxide,
      nitrogen oxide (NO and NO(x)), and carbon monoxide levels. CONCLUSIONS: Asthma
      exacerbations are commonly associated with cold symptoms. These episodes are
      associated with higher levels of sulfur dioxide and nitrogen oxides from March to
      November in comparison with asthma exacerbations without cold symptoms.

PMID- 11447383
TI  - GRbeta expression in nasal polyp inflammatory cells and its relationship to the
      anti-inflammatory effects of intranasal fluticasone.
AB  - BACKGROUND: Nasal polyposis disease is an inflammatory disorder with intense
      eosinophilic infiltration of respiratory mucosa that is often difficult to
      control with topical steroids. Recent evidence suggests that overexpression of
      the glucocorticoid receptor splice variant GRbeta in inflammatory cells might
      contribute to steroid insensitivity in diseases such as asthma. OBJECTIVE: The
      purposes of this investigation were to determine whether nasal polyp (NP)
      inflammatory cells overexpress GRbeta and to examine whether GRbeta
      overexpression is associated with insensitivity to the potent topical steroid
      fluticasone propionate (FP). METHODS: Biopsies were obtained from 10 subjects
      with NPs before and 4 weeks after treatment with intranasal FP. Middle turbinates
      biopsies from 6 healthy, nonallergic subjects served as normal controls. Biopsies
      were immunostained for inflammatory cell markers as well as GRbeta and probed for
      various cytokine mRNA. The anti-inflammatory response to FP was examined in
      relation to pretreatment levels of GRbeta expression. RESULTS: The total numbers
      of inflammatory cells were increased in NPs. The percentage of inflammatory cells
      expressing GRbeta was also increased (40.5% +/- 19.2% vs 16.1% +/- 4.0%, P
      =.009). GRbeta expression in NPs was almost exclusive to T lymphocytes,
      eosinophils, and macrophages. An inverse correlation was observed between the
      baseline inflammatory cell GRbeta expression and the reduction after FP treatment
      in EG2-positive eosinophils, CD4-positive T lymphocytes, endothelial VCAM-1
      expression, and IL-4 mRNA-positive cells. NPs that were "FP-insensitive" in terms
      of suppression of eosinophil numbers (major basic protein-positive) had a
      significantly greater percentage of GRbeta-positive inflammatory cells, a higher
      ratio of GRbeta-positive/GRalpha-positive cells, and increased numbers of GRbeta
      positive eosinophils and macrophages in comparison with those that were "FP
      sensitive." "FP-insensitive" NPs also demonstrated a higher percentage of IL-5
      positive inflammatory cells expressing GRbeta before and after FP treatment.
      CONCLUSION: GRbeta expression appears to be a marker of steroid insensitivity in
      NPs. Expression of GRbeta by NP inflammatory cells, particularly T cells and
      eosinophils, might render them resistant to suppression by topical steroids and
      thereby contribute to persistent NP inflammation.

PMID- 11447384
TI  - The role of the C-C chemokine receptor-5 Delta32 polymorphism in asthma and in
      the production of regulated on activation, normal T cells expressed and secreted.
AB  - BACKGROUND: There are conflicting data regarding the role of a deletion in the C
      C chemokine receptor-5 gene (CCR5*D32) in the pathogenesis of asthma and whether
      this deletion influences the production of regulated on activation, normal T
      cells expressed and secreted (RANTES). RANTES is a chemokine that is known to
      play an important role in the pathogenesis of allergic asthma. OBJECTIVE: We
      sought to determine whether CCR5*D32 is associated with increased RANTES
      production, the presence of asthma, and the severity of asthma. METHODS: A PCR
      assay for CCR5*D32 was developed. The prevalence of CCR5*D32 was determined in a
      group of patients with mild-to-moderate asthma, a group of subjects with severe
      asthma who had fatal or near-fatal asthma attacks, and a group of nonasthmatic
      control subjects. The level of RANTES produced by stimulated and unstimulated T
      cells was measured by using a commercially available immunoassay. RESULTS: The
      frequency of CCR5*D32 was not significantly increased in the severe asthma group
      compared with in the mild-to-moderate asthma group. CCR5*D32 was not increased in
      the asthmatic subjects versus in the control subjects. There was no significant
      increase in RANTES levels from T cells heterozygous for CCR5*D32 compared with
      wild-type cells. CONCLUSION: These data indicate that the CCR5*D32 allele is not
      a genetic risk factor for the development of asthma and does not influence
      disease severity. The CCR5*D32 allele does not influence RANTES production in the
      heterozygous state.

PMID- 11447385
TI  - Increased total serum IgE levels in patients with asthma and promoter
      polymorphisms at CTLA4 and FCER1B.
AB  - BACKGROUND: Increasing evidence indicates that total serum IgE levels are largely
      determined by genetic factors, and we recently established that the -109C/T
      promoter polymorphism at FCER1B is a genetic factor that affects total serum IgE
      levels. The gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) is another
      candidate factor in high IgE responsiveness, because B7-CD28/CTLA4 interaction
      can promote the differentiation and development of the T(H)2 lymphocyte subset.
      OBJECTIVE: We intended to determine whether CTLA4 is associated with increased
      levels of total serum IgE or with the development of asthma or atopy. METHODS: We
      performed a case-control study involving 339 patients with asthma and 305 healthy
      control subjects, of whom 226 of the patients with asthma and 219 of the healthy
      control subjects had previously been genotyped for the -109C/T promoter
      polymorphism at FCER1B. In the current study, we genotyped 2 polymorphisms in the
      CTLA4 gene, one involving the promoter (-318C/T) and the other involving exon 1
      (+49A/G), in addition to the FCER1B promoter polymorphism. RESULTS: Patients with
      asthma who were homozygous for the -318C allele at the CTLA4 promoter region had
      higher levels of total serum IgE than patients with asthma carrying the -318T
      allele (P =.00470). The analysis of -318C/T (at CTLA4) and -109C/T (at FCER1B)
      promoter polymorphisms showed a significant correlation between the combined
      genotypes and increased levels of total IgE in patients with asthma (P =.000014).
      In contrast, no correlation between total serum IgE levels and -318C/T or +49A/G
      genotypes was detected in 305 healthy control subjects. There was no evidence
      indicating an association between a putative allele for asthma or atopy and
      alleles at any of the CTLA4 polymorphic loci. CONCLUSION: Our findings suggest
      that promoter polymorphisms of both CTLA4 and FCER1B are genetic factors that
      influence total serum IgE levels in patients with asthma. This supports the
      theory that variance in total serum IgE levels in patients with asthma is
      determined by mutations in multiple genes, each of which has a relatively small
      effect on the phenotype.

PMID- 11447386
TI  - Autocrine regulation of cord blood-derived human mast cell activation by IL-10.
AB  - BACKGROUND: Ligation of the high-affinity receptor for IgE on human mast cells
      (MCs) induces the release of proinflammatory mediators, including vasoactive
      amines and cytokines (TNF-alpha, IL-5, and IL-8). Moreover, we have recently
      shown that IL-10 inhibits the release of proinflammatory mediators by activated
      MCs. OBJECTIVE: We investigated whether human cord blood-derived MCs (CBMCs)
      could produce IL-10 and whether this production could inhibit their activation in
      an autocrine fashion. METHODS: IL-10 synthesis by resting or activated human MCs
      derived from cord blood progenitors was investigated in cell supernatants or by
      using immunostaining and RT-PCR methods. In addition, the effect of IL-4 on such
      synthesis was also studied. Anti-IL-10-neutralizing antibodies were used to
      investigate the validity of the hypothesis of an autocrine regulation of MCs by
      IL-10. Finally, the presence of specific receptors for IL-10 was searched on
      human CBMCs by using flow cytometric analysis. RESULTS: Human CBMCs spontaneously
      synthesize and release IL-10, and this synthesis is increased after IgE/anti-IgE
      stimulation. In addition, the presence of IL-10 in resting or in activated MCs
      was proved by immunostaining. Interestingly, the release of IL-10 was also
      increased after incubation of the cells with IL-4. Besides, the use of
      neutralizing antibodies against IL-10 confirmed that IL-10 released inhibited MC
      activation in an autocrine fashion. Finally, the presence of specific receptors
      for this cytokine was observed on the membranes of our population of human CBMCs.
      CONCLUSION: Taken together, our data are in favor of an autocrine regulation
      pathway through synthesis and release of IL-10 by human MCs. Such an
      autoregulatory mechanism is, to our knowledge, the first described for these
      elements.

PMID- 11447387
TI  - Proinflammatory cytokines and eosinophil cationic protein on glandular secretion
      from human nasal mucosa: regulation by corticosteroids.
AB  - BACKGROUND: Airway hypersecretion is a common finding in rhinitis and asthma in
      which proinflammatory cytokines are upregulated. The effect of inflammation on
      glandular secretion remains unclear. OBJECTIVE: We sought to investigate the
      effect of proinflammatory cytokines and eosinophil products in in vitro
      lactoferrin glandular secretion from human nasal mucosa and the role of
      corticosteroids and IL-10 in modulating this effect. METHODS: Nasal explants from
      patients undergoing turbinectomies were incubated in a controlled atmosphere (50%
      N(2), 5% CO(2), and 45% O(2)) at 37 degrees C. Nasal explants were incubated with
      or without IL-1beta, IL-4, IL-5, IL-8, eotaxin, GM-CSF, TNF-alpha, eosinophil
      cationic protein (ECP), IL-10, and budesonide in a time-course and dose-response
      fashion. Lactoferrin concentrations in culture supernatants were measured by
      means of ELISA. RESULTS: ECP (up to 30%) caused a dose-related stimulation of
      lactoferrin secretion. TNF-alpha (20 ng/mL) induced a significant increase of
      lactoferrin release from 8 hours (27.7% +/- 17.8%, P <.05) to 24 hours (40.8% +/-
      17.2%, P <.01) compared with that found in media-treated explants. At 24 hours,
      TNF-alpha caused a dose-related stimulation of lactoferrin secretion (up to 35%).
      IL-1beta (65.3% +/- 15.2%, P <.05) and GM-CSF (15.7% +/- 6.7%, P <.05), both at
      20 ng/mL, exerted a stimulatory effect only at 24 hours, and IL-4, IL-5, IL-8,
      and eotaxin had no significant effect. Budesonide caused a dose-related
      inhibition of lactoferrin secretion induced by IL-1beta (down to -76%) and TNF
      alpha (down to -70%), whereas IL-10 had no effect. CONCLUSIONS: ECP and some
      proinflammatory cytokines (IL-1beta, TNF-alpha, and GM-CSF) may contribute to
      glandular hypersecretion in the inflamed nose. Corticosteroids may reduce nasal
      hypersecretion by blocking the direct effect of proinflammatory cytokines on
      glandular output.

PMID- 11447388
TI  - Preclinical evaluation of an immunotherapeutic peptide comprising 7 T-cell
      determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens.
AB  - BACKGROUND: Peptide immunotherapy is a new approach to treating allergic
      diseases, but a therapeutic peptide for Japanese cedar pollinosis has not yet
      been developed. OBJECTIVE: The aim of this study is to prepare and preclinically
      evaluate a hybrid peptide comprising 7 T-cell determinants of Cry j 1 and Cry j
      2, the major Japanese cedar pollen allergens. METHODS: The recombinant hybrid
      peptide was prepared after immunodominance of 7 T-cell determinants was confirmed
      by means of PBMC proliferation assay in 113 volunteers with pollinosis. The
      hybrid peptide was compared with a mixture of the 7 T-cell determinants in a dose
      dependent PBMC proliferation assay in 6 volunteers with pollinosis. PBMC
      proliferation and binding activity of serum IgE antibody against the hybrid
      peptide, Cry j 1, and Cry j 2 were investigated in 48 volunteers with pollinosis.
      RESULTS: The hybrid peptide induced T-cell proliferation with an average 100-fold
      lower concentration than a mixture of the 7 peptides. PBMCs from 44 (92%) of 48
      volunteers proliferated against the hybrid peptide, with significant correlation
      (r = 0.87) in T-cell proliferation against Cry j 1 and Cry j 2. No serum IgE
      antibodies specific to Cry j 1 or Cry j 2 bound to the hybrid peptide.
      CONCLUSION: A hybrid peptide comprising 7 T-cell determinants has the potential
      for inducing T-cell proliferative responses that is superior to the potential of
      a mixture of the T-cell determinants and comparable with that of Cry j 1 and Cry
      j 2. The hybrid peptide will be of use in specific immunotherapy against Japanese
      cedar pollinosis.

PMID- 11447389
TI  - Roles of carbohydrates on Cry j 1, the major allergen of Japanese cedar pollen,
      in specific T-cell responses.
AB  - BACKGROUND: Carbohydrates expressed on allergens are known to be important for
      allergenicity. However, little is known about whether the carbohydrates drive the
      T(H)2 response. OBJECTIVE: We sought to determine a role for carbohydrates
      expressed on Cry j 1, which is the major allergen of Cryptomeria japonica pollen
      and causes the most prevalent pollinosis in Japan, in in vitro cellular
      responses. METHODS: Carbohydrates on Cry j 1 were destroyed by periodate
      oxidation under mild conditions. Proliferative responses and cytokine productions
      against native, periodate-treated, and mock-treated Cry j 1 were compared in
      peripheral blood mononuclear cells, Cry j 1-specific T-cell lines, and clones
      from patients with Japanese cedar pollinosis. RESULTS: We found that peripheral
      blood mononuclear cells from patients with Japanese cedar pollinosis displayed a
      significant decrease in proliferation and IL-5 production in response to
      periodate-treated Cry j 1 in comparison with native and mock-treated Cry j 1.
      Decreased proliferative responses against periodate-treated Cry j 1 were also
      seen in polyclonal T-cell lines, and the responses showed a heterogeneity. In
      addition, Cry j 1-specific CD4+ T-cell clones also displayed a significant
      decrease in proliferation and IL-4 and IL-5 production-but not IFN-gamma
      production-in comparison with the control antigens. However, most of the clones
      showed decreased but positive proliferative responses against periodate-treated
      Cry j 1. Blockade of the mannose receptor had no effect on cellular responses.
      CONCLUSION: The results suggest that carbohydrates on Cry j 1 play a major role
      in promoting Cry j 1-specific T(H)2 response in vitro, though they are not major
      targets as T-cell epitopes.

PMID- 11447390
TI  - Release of allergen-bearing cytoplasm from hydrated pollen: a mechanism common to
      a variety of grass (Poaceae) species revealed by electron microscopy.
AB  - BACKGROUND: The release of submicronic particles from grass pollen after rainfall
      was suggested to be responsible for outbreaks of grass pollen asthma. Recently,
      we provided evidence for the release of respirable allergen-bearing particles
      from hydrated ryegrass (Lolium perenne ) pollen as a possible explanation for
      this phenomenon. OBJECTIVE: We investigated whether water-induced release of
      respirable allergen-bearing particles could be a mechanism common to several
      members of the sweet grass family Poaceae (Gramineae). METHODS: Pollens from 6
      different Poaceae species were hydrated in water and examined by means of
      scanning electron microscopy for release of cytoplasmic materials. Rabbit
      antisera raised against purified recombinant group 1 and 5 allergens were used
      for immunogold labeling of expelled materials by means of field emission scanning
      electron microscopy. In addition, group 1 and 5 allergens were immunogold
      localized on ultrathin sections. RESULTS: Fresh Poaceae pollens expelled
      cytoplasmic materials containing group 1 and 5 allergens on hydration in water.
      Expulsion of submicronic particles strongly decreased after 1 month of storage.
      CONCLUSIONS: Our results suggest expulsion of cytoplasm after hydration as a
      mechanism common to pollens of important allergenic grasses. The water-induced
      release of respirable allergen-bearing particles from grass pollens might explain
      asthma attacks observed after rainfall during the grass pollen season.

PMID- 11447391
TI  - IgE-mediated mast cell degranulation and recovery monitored by time-lapse
      photography.
AB  - BACKGROUND: Mast cells are long-lived resident cells that are of great importance
      in an allergic reaction. It has previously been suggested that after IgE-mediated
      degranulation mast cells can undergo regranulation. Such a process is probably of
      great importance with respect to the severity and perpetuation of the allergic
      response. OBJECTIVE: Our purpose was to investigate whether mast cells recover
      from degranulation and whether they still have the potential to release a granule
      associated mediator and upregulate certain cytokine genes. METHODS: Mouse mast
      cells were repeatedly activated by IgE and specific antigen with a 24-hour or 48
      hour interval. During each of the 2 activation stages, release of beta
      hexosaminidase was measured by means of enzymatic colorimetric analysis, and IL
      13 and IL-6 mRNA was detected by ribonuclease protection assay. Both scanning
      electron microscopy and time-lapse photography were used to reveal the process of
      mast cell recovery. RESULTS: We found that re-activation of degranulated mast
      cells in response to high-affinity IgE-receptor cross-linkage triggers beta
      hexosaminidase release and upregulation of IL-13 and IL-6 gene expression levels
      similar to what is seen in the initial activation. Scanning electron microscopy
      documented cells at various stages during the recovery process 30 minutes after
      the activation. With time-lapse photography, a single cell that had undergone
      degranulation could be visualized consecutively during its recovery process.
      CONCLUSION: Mast cells can recover after an IgE-mediated activation and can
      repeatedly release beta-hexosaminidase and express IL-6 and IL-13 mRNA after re
      activation.

PMID- 11447392
TI  - A novel pharmacologic action of glucocorticosteroids on leukotriene C4
      catabolism.
AB  - Leukotriene (LT) C(4), a potent chemical mediator in human bronchial asthma, is
      metabolized to less active LTE(4) via LTD(4) in 2 consecutive enzymatic reactions
      by gamma-glutamyl transpeptidases and dipeptidases. We examined whether this
      inactivation process of LTC(4) was affected by fluticasone propionate,
      beclomethasone dipropionate, disodium cromoglycate, and salbutamol sulfate in
      transformed human bronchial epithelial cells. Fluticasone propionate and
      beclomethasone dipropionate accelerated LTC(4) catabolism by inducing activity of
      a LTC(4)-degrading enzyme, gamma-glutamyl transpeptidase-related enzyme (gamma
      GTPRE), in transformed human bronchial epithelial cells. The activation of gamma
      GTPRE might be regulated transcriptionally. This is a novel regulatory mechanism
      by which glucocorticosteroids exert antiasthma activities.

PMID- 11447393
TI  - Rhinoconjunctivitis and occupational asthma caused by Diplotaxis erucoides (wall
      rocket).
AB  - Wall rocket (Diplotaxis erucoides) is a common Crucifera plant that grows in
      European and American vineyards and olive groves. We present the cases of 2
      farmers with rhinoconjunctivitis and asthma related to wine-growing tasks during
      D erucoides pollination (March-April). The aim of this work was to demonstrate
      that occupational symptoms were caused by D erucoides pollen sensitization.
      Cutaneous tests, specific IgE measurements, conjunctival and bronchial
      provocation tests, and peak-flow measurements during working days were performed.

PMID- 11447394
TI  - A voluntary registry for peanut and tree nut allergy: characteristics of the
      first 5149 registrants.
AB  - BACKGROUND: A voluntary registry of individuals with peanut and/or tree nut
      allergy was established in 1997 to learn more about these food allergies.
      OBJECTIVE: The purpose of this study was to elucidate a variety of features of
      peanut and tree nut allergy among the first 5149 registry participants. METHODS:
      The registry was established through use of a structured questionnaire
      distributed to all members of the Food Allergy and Anaphylaxis Network and to
      patients by allergists. Parental surrogates completed the forms for children
      under the age of 18 years. RESULTS: Registrants were primarily children (89% of
      registrants were younger than 18 years of age; the median age was 5 years),
      reflecting the membership of the Network. Isolated peanut allergy was reported by
      3482 registrants (68%), isolated tree nut allergy by 464 (9%), and allergy to
      both foods by 1203 (23%). Registrants were more likely to have been born in
      October, November, or December (odds ratio, 1.2; 95% CI, 1.18-1.23; P <.0001).
      The median age of reaction to peanut was 14 months, and the median age of
      reaction to tree nuts was 36 months; these represented the first known exposure
      for 74% and 68% of registrants, respectively. One half of the reactions involved
      more than 1 organ system, and more than 75% required treatment, frequently from
      medical personnel. Registrants with asthma were more likely than those without
      asthma to have severe reactions (33% vs 21%; P <.0001). In comparison with
      initial reactions, subsequent reactions due to accidental ingestion were more
      severe, more common outside the home, and more likely to be treated with
      epinephrine. CONCLUSIONS: Allergic reactions to peanut and tree nut are
      frequently severe, often occur on the first known exposure, and can become more
      severe over time.

PMID- 11447395
TI  - Population study of food allergy in France.
AB  - BACKGROUND: Food allergy (FA) is an important health problem for which
      epidemiologic studies are needed. OBJECTIVE: We performed an epidemiologic survey
      in France to determine the prevalence, clinical pictures, allergens, and risk
      factors of FA. METHODS: This study was conducted on 33,110 persons who answered a
      questionnaire addressed to a representative sample of the French population on a
      scale of 1:1000 (44,000 subjects aged </=60 years). One thousand one hundred
      twenty-nine persons with FA selected during phase 1 received a second
      questionnaire. RESULTS: The reported prevalence of FA is 3.52%: 3.24%
      evolutionary FA; 0.12% asymptomatic cases thanks to eviction diets; and 0.17%
      cured FA. The subjects were characterized by overrepresentation of city dwellers
      (80% vs 76%), women (63% vs 50%), and health care personnel (11% vs 4%). Fifty
      seven percent (vs 17%) presented with atopic diseases (P <.01). FA was often
      persistent, lasting more than 7 years in 91% of the adults. The most frequent
      allergens were 14% Rosaceae, 9% vegetables, 8% milk, 8% crustaceans, 5% fruit
      cross-reacting with latex, 4% egg, 3% tree nuts, and 1% peanut. Sensitization to
      pollen was significantly correlated with angioedema, asthma, rhinitis, and fruit
      allergy (P <.01). FA was 4 times more frequent in patients with latex allergy.
      The main manifestations of FA were atopic dermatitis for subjects under 6 years
      of age, asthma for subjects between 4 and 6 years of age, and anaphylactic shock
      in adults over 30 years of age (P <.007). Shocks were correlated with alcohol or
      nonsteroidal anti-inflammatory drug intake (P <.01 and P <.04, respectively).
      CONCLUSION: The prevalence of FA is estimated at 3.24% (range, 3.04% to 3.44%) in
      France. This study emphasizes the increasing risk of FA in well-developed
      countries and draws attention to certain FA risk factors, such as the intake of
      drugs (nonsteroidal anti-inflammatory drugs, beta-blockers, and angiotensin
      converting enzyme inhibitors) or alcohol, intolerance of latex gloves, and
      socioprofessional status.

PMID- 11447396
TI  - Successful prevention of recurrent nasal polyposis by means of systemic low-dose
      IFN-alpha2a.

PMID- 11447397
TI  - Eosinophil levels in mice are significantly higher in small blood vessels than in
      large blood vessels.

PMID- 11447398
TI  - Chronic cough due to latex-induced eosinophilic bronchitis.

PMID- 11447399
TI  - Differences in Bifidobacterium flora composition in allergic and healthy infants.

PMID- 11447400
TI  - Unexpected spice allergy in the meat industry.

PMID- 11447401
TI  - A lipid transfer protein involved in occupational sensitization to spelt.

PMID- 11447402
TI  - Food allergy after pediatric organ transplantation with tacrolimus
      immunosuppression.

PMID- 11447403
TI  - Role of mometasone furoate nasal spray as an adjunct treatment of acute
      sinusitis.

PMID- 11447405
TI  - Adverse and allergic reactions in complementary and alternative medicine.

PMID- 11447407
TI  - CD63 expression on basophils of nonallergic controls and patients allergic to
      wasp.

PMID- 11447410
TI  - Prospective study of routine perioperative transesophageal echocardiography for
      elective valve replacement: clinical impact and cost-saving implications.
AB  - Transesophageal echocardiography (TEE) is widely used during heart valve
      replacement operations, but its clinical impact and cost-saving profile have not
      been studied prospectively for this indication. We investigated the clinical
      benefits and cost-savings of routine TEE for elective valve replacement at a
      regional tertiary center. We prospectively studied 300 patients (140 men; mean
      age [+/-SD], 66 +/- 9 years) undergoing aortic valve, mitral valve, or double
      valve replacements. Transesophageal echocardiography with a biplane (in 161
      patients) or a multiplane probe was performed before and after surgery. We
      assessed whether the TEE findings changed the operation or the postoperative
      treatment and the cost of TEE either as an extension of a preexisting service or
      as a new development. In 2 patients undergoing aortic valve replacement,
      significant mitral regurgitation on TEE led to additional mitral valve
      replacement, and in 1 patient undergoing mitral valve replacement, aortic
      regurgitation also required aortic valve replacement. Immediate reoperation
      (dehisced mitral valve prosthesis) and delayed extubation (suspected obstruction
      of an aortic valve prosthesis) were prompted by postoperative TEE. Extending an
      existing TEE service to routine intraoperative use saved up to $109 (US) per
      patient per year. Routine intraoperative TEE can provide major clinical benefit
      to a small proportion of patients undergoing elective valve replacement, and this
      can lead to cost savings, but only if the service can be provided without major
      capital investment.

PMID- 11447411
TI  - Milrinone echocardiographic viability test: a pilot study.
AB  - We assessed the utility of milrinone to predict recovery of function after
      surgical myocardial revascularization in patients with severe baseline left
      ventricular systolic dysfunction caused by coronary artery disease (CAD).
      Prediction of viable myocardial segments that will regain function after
      revascularization may help in the selection of patients who will benefit from
      coronary artery bypass graft surgery (CABG) as well as aid in the choice of
      target sites for coronary revascularization. We investigated 20 consecutive
      patients with CAD and left ventricular ejection fraction < or = 40% who had
      evidence of myocardial viability by either thallium scan or dobutamine viability
      test and were candidates for elective CABG. Left ventricular regional wall motion
      and global ejection fraction were assessed by transesophageal echocardiography in
      the operating room. Measurements were done before and 10 minutes after milrinone
      infusion, and immediately after CABG. Left ventricular wall motion score was
      derived by means of a 12-segment model. Functional improvement for each segment
      was defined as a wall motion change > 1. Baseline ejection fraction was 27% +/-
      5% (mean +/- SD). Ejection fraction increased to 35% +/- 5% after milrinone
      infusion (P < .0001) and to 36% +/- 6% after CABG (P < .0001). Post-CABG ejection
      fraction was significantly correlated with postmilrinone ejection fraction (r =
      0.65, P < .0001). Milrinone infusion resulted in augmentation of contraction in
      98 of the 209 abnormal segments (wall motion score > or = 2); 91 (92.9%) of these
      improved after CABG. One hundred nine of the 111 segments that showed no
      improvement with milrinone did not improve after revascularization (98.2%).
      Seventy-three segments were akinetic or dyskinetic at baseline; 46 (63.0%) of
      these improved with milrinone. Improvement in regional wall motion after
      revascularization was detected in 84.8% of the segments that improved with
      milrinone versus only 3.7% of the segments that did not improve with milrinone.
      In patients with ischemic cardiomyopathy, improvement in left ventricular
      function (segmental wall motion and global ejection fraction) during milrinone
      infusion is highly predictive of improvement after CABG.

PMID- 11447412
TI  - Utility of stress Doppler echocardiography in patients undergoing percutaneous
      mitral balloon valvotomy.
AB  - A subset of patients with mitral stenosis have symptoms out of proportion to the
      resting hemodynamics. Exercise Doppler echocardiography is a useful diagnostic
      modality to determine which patients are limited by their valve obstruction and
      would therefore benefit from percutaneous mitral balloon valvotomy. We analyzed
      11 patients who showed a peak exercise mean mitral gradient that doubled from
      baseline or a final gradient of > 15 mm Hg. The mean mitral gradient increased
      from 7 +/- 2 mm Hg at rest to 19 +/- 6 mm Hg (P < .001) with exercise. All
      patients reported improvement in symptoms of at least 1 functional class after
      valvotomy.

PMID- 11447413
TI  - Dipyridamole stress ultrasonic myocardial tissue characterization in patients
      with Kawasaki disease.
AB  - Dipyridamole stress integrated backscatter (IBS) was used for evaluation of
      myocardial ischemia or damage in 31 children with coronary artery lesions caused
      by Kawasaki disease, in comparison with thallium-201 myocardial imaging. All
      patients underwent echocardiography at rest and after dipyridamole stress at the
      anterior interventricular septum, posterior wall (PW), and inferior wall (INF).
      At rest, no significant difference was seen in cyclic variation (CV) of IBS in
      the regions with normal or abnormal distribution on Tl-201 imaging. But in the
      regions showing abnormal distribution after stress, CV decreased significantly. A
      delayed study after stress showed the recovery of CV to the level at rest in all
      patients. Sensitivity of abnormal cyclic variation integrated backscatter was 75%
      in the PW and 91% in the INF, and specificity was 91% in the PW and 90% in the
      INF, compared with the results of thallium-201 imaging. Dipyridamole stress IBS
      can provide sensitive detection of myocardial ischemia or damage in Kawasaki
      disease.

PMID- 11447414
TI  - Changes in systolic and postsystolic wall thickening during acute coronary
      occlusion and reperfusion in closed-chest pigs: Implications for the assessment
      of regional myocardial function.
AB  - The aim of the study was to characterize the impact of short-lived total coronary
      occlusions in closed-chest pigs on radial wall thickening within the "at-risk"
      myocardial segment by using gray-scale M-mode echocardiography. Twelve pigs
      underwent a series of 20-second total circumflex coronary artery occlusions with
      an angioplasty balloon. Myocardial thickening/thinning indexes were continuously
      monitored before ischemia, during ischemia, and on reperfusion by high-resolution
      M-mode recordings of the posterior wall obtained from parasternal views. The
      timing of regional events was compared with global systolic time intervals
      derived from the color Doppler myocardial imaging velocity data. Each occlusion
      induced a rapid decrease in end-systolic thickening (epsilon(ES)), closely
      paralleled by an increase in postsystolic thickening in the ischemic segment.
      After 20 seconds of ischemia, epsilon(ES) decreased by -86% and postsystolic
      thickening increased by +100%, whereas maximal thickening decreased only by -34%
      in comparison with preocclusion values. All wall thickening parameters returned
      to baseline after 15 seconds of reperfusion. During acute total ischemia in a
      closed-chest animal model, the changes in regional myocardial function were best
      characterized by the combined analysis of systolic and postsystolic thickening
      abnormalities and by their respective timings relative to global cardiac events
      markers.

PMID- 11447415
TI  - Real-time myocardial blood flow imaging in normal human beings with the use of
      myocardial contrast echocardiography.
AB  - Triggered myocardial contrast echocardiography (MCE) has been used successfully
      to quantify myocardial blood flow and assess coronary stenosis in animal models,
      but practical considerations have limited its broad clinical use. Real-time MCE
      may have practical advantages to assess perfusion and real time myocardial blood
      flow in human beings. We compared real-time MCE with triggered imaging in 23
      normal human volunteers by using an investigational ultrasound contrast agent
      (DMP-115) and a commercially available ultrasound platform (Acuson Sequoia). Peak
      myocardial opacification (reflecting myocardial blood volume) after contrast
      infusion was quantified digitally in gray scale units (GU). In 13 subjects,
      myocardial blood flow reserve was assessed during dipyridamole infusion with the
      use of intermittent destruction-replenishment techniques. Real-time MCE resulted
      in a 30- to 45-GU increase from baseline compared with a 20- to 70-GU increase
      with triggered imaging. Real-time MCE showed no statistical difference in
      opacification (P = .131 by analysis of variance) among any of the myocardial
      regions of interest. Triggered imaging resulted in heterogeneous opacification
      among the regions of interest (P < .05 by analysis of variance). Dipyridamole did
      not significantly change peak myocardial opacification (myocardial blood volume)
      for either technique. Quantification of flow reserve revealed that myocardial
      blood flow reserve for the dipyridamole group was 3.6 +/- 0.4 (mean +/- 1
      standard error of the mean). Real-time MCE is feasible in normal human volunteers
      and provides homogenous opacification of the myocardium. Furthermore,
      quantification of myocardial blood flow with real-time MCE in normal human beings
      produces results that are consistent with the known physiology of the coronary
      microcirculation.

PMID- 11447416
TI  - Coronary risk area measurement by intracardiac echocardiography and ultrasound
      contrast.
AB  - The perfusion bed of an occluded coronary artery-the coronary risk area
      determines infarct size. Our objective was to evaluate the combined techniques of
      intracardiac echocardiography (ICE) and ultrasound contrast echocardiography for
      real-time estimation of the coronary risk area in an experimental model. We
      studied 13 pigs and 2 dogs. The left anterior descending coronary was occluded by
      inflating coronary balloons. An ultrasound contrast agent was injected either
      through the dilation catheter (distal to the inflated balloon) directly into the
      occluded artery to opacify the "positive" risk area or into the aortic root
      during coronary balloon inflation to determine the nonopacified "negative" risk
      area. Evans blue dye was injected into the occluded artery to stain the risk
      area, allowing an independent measurement. The mean left anterior descending
      negative risk area was 26% +/- 10% of the left ventricular myocardial area, the
      mean positive risk area was 24% +/- 10%, and the Evans blue-stained risk area was
      25% +/- 9%. By Bland-Altman analysis, the positive Optison-Evans blue mean +/- SD
      difference was 1.42% +/- 6.42%; the negative Optison-Evans blue mean +/- SD
      difference was 1.02% +/- 7.56%. Coronary risk area can be determined with
      intracardiac echocardiography and ultrasound contrast.

PMID- 11447417
TI  - Intracardiac echocardiography identifies pericardial fluid and can monitor the
      success of pericardiocentesis: experimental studies.
AB  - Pericardial tamponade is a complication of cardiac catheterization. Our purpose
      was to evaluate the ability of intracardiac echocardiography (ICE) to identify
      pericardial fluid and the success of pericardiocentesis in an experimental model.
      Seven dogs were studied with the use of a 10F, 10-MHz ICE catheter in the left
      ventricle. Normal saline was injected into the pericardial space while heart rate
      and arterial pressure were continuously monitored. The ability of ICE to identify
      the presence of pericardial fluid and the maximum pericardial separation and to
      monitor fluid accumulation and withdrawal was evaluated. Thirteen sequences of
      saline injection/withdrawal were studied. ICE correctly identified the presence
      or absence of pericardial fluid in all 13 injection/withdrawal sequences. The
      average sonolucent space separating epicardium from pericardium was 12 +/- 7 mm,
      generated from 148 +/- 65 mL of saline and producing a 35 +/- 23 mm Hg decrease
      in systolic blood pressure. ICE readily identified the accumulation and removal
      of pericardial fluid in this experimental model and should be an excellent tool
      to monitor pericardiocentesis in the catheterization laboratory.

PMID- 11447418
TI  - Noninvasive assessment of left ventricular isovolumic contraction and relaxation
      with continuous wave Doppler aortic regurgitant velocity signals: an in vivo
      validation study.
AB  - The purpose of this study was to provide fundamental in vivo validation of a
      method with the use of aortic regurgitant (AR) jet signals recorded with
      continuous wave (CW) Doppler for assessing left ventricular (LV) isovolumic
      contraction and relaxation. Preliminary studies have suggested that analysis of
      CW Doppler AR velocity signals permits the estimation of LV positive and negative
      dP/dt. We studied 19 hemodynamically different states in 6 sheep with surgically
      induced chronic aortic regurgitation. CW AR velocity spectra and high-fidelity LV
      and aortic pressures were recorded simultaneously. Rates of LV pressure rise and
      fall (RPR and RPF) were calculated by determining the time interval between
      points at 1 m/s and 2.5 m/s in the deceleration and acceleration slopes of the CW
      Doppler AR velocity envelope (corresponding to a pressure change of 21 mm Hg).
      RPR and RPF calculated by CW Doppler analysis for each state were compared with
      the peak positive dP/dt and negative dP/dt, obtained from the corresponding high
      fidelity LV pressure curve, respectively. The LV peak positive and negative dP/dt
      derived by catheter ranged from 817 to 2625 mm Hg/s and from 917 to 2583 mm Hg/s,
      respectively. Multiple regression analysis showed that Doppler RPR correlated
      well with catheter peak positive dP/dt (r = 0.93; mean differences, -413 +/- 250
      mm Hg/s). There was also good correlation and agreement between Doppler RPF and
      the catheter peak negative dP/dt (r = 0.89; mean difference, -279 +/- 239 mm
      Hg/s). Both Doppler-determined RPR and RPF underestimated their respective LV
      peak dP/dt. CW Doppler AR spectra can provide a reliable noninvasive estimate of
      LV dP/dt and could be helpful in the serial assessment of ventricular function in
      patients with aortic regurgitation.

PMID- 11447419
TI  - Quantitative assessment of mechanical prosthetic valve area by 3-dimensional
      transesophageal echocardiography.
AB  - OBJECTIVE: The goal of this study was to assess the geometric orifice area of
      mechanical valve prostheses by transesophageal 3-dimensional echocardiographic
      planimetry. METHODS AND RESULTS: Currently used Doppler methods for prosthetic
      assessment (orifice area-Doppler) were compared with 3D planimetry for orifice
      area (orifice area-3D) and with manufacturer's values (orifice area-manufacturer)
      for the corresponding prosthesis types and sizes and with historical controls
      provided by Doppler literature (orifice area-literature). Twenty-four mechanical
      valve prostheses (in 22 patients) were studied: 13 in mitral position and 11 in
      aortic position. Orifice area-manufacturer, orifice area-Doppler, orifice area
      literature, and orifice area-3D were 3.6 +/- 1.1 cm(2), 2.3 +/- 0.9 cm(2), 2.4 +/
      0.9 cm(2), and 2.6 +/- 0.7 cm(2), respectively. Orifice area-manufacturer values
      were significantly larger. Correlation coefficients between orifice area-3D and
      orifice area-manufacturer, and between orifice area-3D and orifice area-Doppler
      and orifice area-literature were 0.83, 0.90, and 0.73, respectively (all P <
      .0001). CONCLUSION: Three-dimensional transesophageal echocardiography is
      feasible and has good correlation with orifice area-Doppler (in aortic position)
      and good correlation with orifice area-manufacturer (in aortic and mitral
      positions) methods.

PMID- 11447420
TI  - Deviation of atrial septum primum in association with normal left
      atrioventricular valve size.
AB  - Deviation of atrial septum primum (DASP) is an unusual anatomic finding in
      patients with normal left atrioventricular valve size. To better describe this
      anomaly, we reviewed our echocardiographic database from January 1987 to May
      1999. Twenty-four patients had DASP and a normal-sized left atrioventricular
      valve. Six had inferior DASP with common atrioventricular canal. Of these, 3 had
      evidence of left atrial outlet obstruction. Five survived surgical intervention
      with follow-up of 24 +/- 14 months. Seventeen patients had superoposterior
      deviation with the right pulmonary veins draining anomalously to the right
      atrium. Only 8 of 17 underwent surgical resection; none of the 17 have evidence
      for late development of obstruction. One patient had both inferior deviation and
      superoposterior DASP and underwent early successful repair. DASP occurs in
      patients with normal left atrioventricular valve size. Inferior DASP can result
      in left atrial outlet obstruction and requires surgical intervention.
      Superoposterior DASP carries less physiologic consequence. Echocardiography can
      distinguish this anomaly from other forms of left atrial obstruction.

PMID- 11447421
TI  - Residual sinus venosus atrial septal defect after surgical closure of atrial
      septal defect.
AB  - We describe residual atrial septal defects in 3 patients who had previous
      surgical repair. The residual defects were the sinus venosus type near the
      orifice of the inferior vena cava. Preoperative and intraoperative
      transesophageal echocardiography may aid in the detection and facilitate the
      successful repair of these defects.

PMID- 11447422
TI  - Two- and three-dimensional echocardiographic unroofed coronary sinus.
AB  - We present the 2-dimensional findings and 3-dimensional reconstruction of images
      from an 18-year-old patient with unroofed coronary sinus, persistent left
      superior vena cava, a common atrium with levoisomerism, ventricular septal
      defect, and double-outlet right ventricle. The left superior vena cava showed
      continuity with the floor of the coronary sinus. Diagnosis of the constellation
      of anomalies established by transesophageal reconstruction clarified the
      continuity of the coronary sinus with left superior vena cava and atrial wall.

PMID- 11447423
TI  - Noninvasive diagnosis of partial anomalous left pulmonary artery.
AB  - The branching patterns of the pulmonary arteries may vary, with one or more lobes
      of the left lung being supplied by a branch originating from the right pulmonary
      artery-a condition termed partial anomalous left pulmonary artery. If this
      anomalous branch courses anterior and inferior to the trachea, it is unlikely to
      result in airway obstruction. It is important that this anomaly not be confused
      with pulmonary artery sling, where the anomalous branch courses posterior to the
      trachea, encircling it almost completely. Partial anomalous left pulmonary artery
      has previously been diagnosed with angiography or by direct visualization during
      surgery. We present the first cases of noninvasive diagnosis of this anomaly with
      the use of echocardiography and magnetic resonance imaging. The complementary
      roles of these two modalities in detecting the anomaly and defining the spatial
      relationship of the anomalous pulmonary artery to the trachea are emphasized.

PMID- 11447424
TI  - Unrecognized esophageal perforation in a neonate during transesophageal
      echocardiography.
AB  - Esophageal perforation caused by transesophageal echocardiography in an infant is
      believed to be extremely rare. If unrecognized, serious morbidity can result. We
      report a case of pharyngeal perforation in a neonate undergoing an interrupted
      aortic arch repair.

PMID- 11447425
TI  - Value of repeated multiplane transesophageal echocardiography in a patient with
      mitral valve ring abscess and left ventricular pseudoaneurysm.
AB  - Mitral valve ring abscess and ventricular pseudoaneurysm are rare complications
      of infective endocarditis. We describe the case of a 58-year-old man who was
      admitted to our hospital with sepsis caused by Staphylococcus aureus and in whom
      tricuspid and mitral valve endocarditis developed within 2 weeks. Despite
      widespread antibiotic therapy, the endocarditis proceeded to form a mitral valve
      ring abscess and a left ventricular pseudoaneurysm. The diagnosis was set by
      repeated multiplane transesophageal echocardiography and confirmed by heart
      surgery.

PMID- 11447426
TI  - Acute myocardial infarction caused by coronary embolism complicated by left
      ventricular free wall rupture.
AB  - Acute myocardial infarction with normal coronary arteries is a relatively
      infrequent finding. This report describes a rare combination of an embolic event
      to a normal coronary artery, presumably originating from a left atrial thrombus.
      An anomalous origin of the infarct-related coronary artery presumably enabled
      preferential penetration of the clot into the artery. The infarction was further
      complicated by rupture of the left ventricular free wall.

PMID- 11447427
TI  - Surgery for ossification of the posterior longitudinal ligament of the cervical
      spine.
AB  - The authors present their surgical experience with fifty seven cases of
      ossification of the posterior longitudinal ligament (OPLL) of the cervical spine,
      operated between January 1992 and January 1999. Continuous OPLL was seen in the
      majority of patients (40/57). Posterior decompressive surgery was performed in 18
      patients, a median corpectomy and excision of the OPLL in 28 and anterior
      segmental decompression in 11 patients. One patient had a transient weakness of
      muscles supplied by the C5 myotome following a C4-C5 corpectomy. 84.2% of the
      patients showed improvement by at least one grade at the time of discharge. 92.8%
      of patients who underwent a corpectomy improved in the immediate post-operative
      period as compared to 90.9% of those who underwent an anterior segmental
      decompression and 83.3% of those who underwent a posterior decompressive
      procedure. 97.7% of the 44 patients followed-up between one and five years showed
      neurological improvement. Thirty-two patients (72.7 %) had regained normal or
      near normal neurological function and returned to their jobs. Good results were
      obtained when the surgical approach and the procedure adopted were
      individualised.

PMID- 11447428
TI  - Ischaemic strokes: management in first six hours.
AB  - Cerebrovascular disease (CVD) or stroke is one of the foremost causes of high
      morbidity and mortality for many nations of the world, posing a major socio
      economic challenge in the occupational and neuro-rehabilitational programmes of
      the 'stroke-survivors'. For example, in USA alone it has been estimated that a
      sum of 3261 million dollars is spent as direct cost for treatment, in addition to
      4104 million dollars as indirect costs, consequent on economic losses of 'stroke
      victims'. Thus, the new concept in stroke pathophysiology and strategies for
      stroke prevention have assumed global importance. Among all risk factors for
      strokes, hypertension is one of the most important and treatable factor.
      Community screening surveys, by well defined WHO protocol, have shown that nearly
      15% of urban population is hypertensive (160/95 mm Hg or more). Though high blood
      pressure has the highest attributable risk for stroke, there are many other
      reasons such as patient's compliance in taking medicine and poor followup in
      clinical practice that may lead to failure in reducing stroke mortality. In
      subjects, who have transient ischaemic attacks (TIAs), regular use of
      antiplatelet agents like aspirin is well established in prevention of stroke. It
      is also mandatory to prohibit tobacco use and adjust dietary habits to control
      body weight. Associated conditions like diabetes mellitus etc. should also be
      treated. It is advisable to initiate community screening surveys on well defined
      populations for early detection of hypertension and TIAs. Primary health care
      centres should be the base stations for these surveys, because data gathered from
      urban hospitals will not truly reflect the crude prevalence rates for the
      community to design practical prevention programmes.

PMID- 11447429
TI  - Flowcytometric and histopathological correlation of primary intracranial
      neoplasms.
AB  - DNA ploidy and synthetic phase fraction (SPF) of 52 cases of primary intracranial
      neoplasms have been determined from fresh tissues and the data was correlated
      with histopathological typing and grading. Fresh tumour tissues from 52 random
      surgical biopsies (28 malignant and 24 benign) were obtained from neurosurgical
      operations during the period 1994-1996. The cells were analysed in Becton
      Dickinson flowcytometer fitted with Consort 30 programme and 'Sober' software.
      Percentage of diploid cells, proliferative cells and DNA aneuploidy were
      evaluated. The tumours were classified and graded according to WHO classification
      (1993). On histology, there were 28 malignant (grade II to IV) and 24 benign
      cases (grade I). All the histologically benign tumours in this study showed
      diploid DNA content with the exception of a pituitary adenoma which had a
      heterogeneous population of cells. The S phase fraction in all the benign cases
      was less than 10% except in the case of choroid plexus papilloma (S-phase 54%)
      and an atypical meningioma (S-phase 14%). Out of the 28 malignant tumours, 12
      cases were aneuploid (43%) and the rest were diploid (57%). Among the 16 diploid
      tumours, SPF was more than 10% in eight cases. DNA aneuploidy and high SPF are
      more common in histologically malignant tumours than benign tumours. SPF is a
      reflection of proliferation potential of a tumour and may have some role in
      prognostication of brain tumours.

PMID- 11447430
TI  - Split cord malformation (scm) in paediatric patients: outcome of 19 cases.
AB  - There had been considerable debate regarding the surgical outcome of neuro
      orthopaedic syndromes (NOS) and neurological syndromes in cases of split cord
      malformation (SCM). On retrospective analysis of 19 cases of SCM, thirteen were
      grouped under (Pang) type I and 6 in type II. Their age ranged from 1 month to 9
      years (mean 3.5 years). 14 of these were male children. The NOS without
      neurological signs was detected in 6 cases where as pure neurological signs
      without NOS were seen in 8 patients. However, the rest 5 had mixed picture of NOS
      and neurological dysfunction. Nine of 19 cases presented with cutaneous stigmata,
      mainly in the form of hairy patch. 18 cases had other associated craniospinal
      anomalies i.e. hydrocephalus, meningomyelocoele, syrinx, dermoid, teratoma etc.
      Detethering of cord was done in all cases by removal of fibrous/bony septum.
      Associated anomalies were also treated accordingly. Follow up of these cases
      ranged from 6 months to 6 years. Six cases of NOS group neither showed
      deterioration nor improvement, and remained static on follow up. However, four of
      8 children with neurological signs showed improvement in their motor weakness,
      and 1 in saddle hypoaesthesia as well as bladder/bowel function. In 5 cases of
      mixed group, two had improvement in their weakness and one in hypoaesthesia, but
      no change was noticed in NOS of this group as well. Hence surgery seemed to be
      effective, particularly in patients with neurological dysfunction.

PMID- 11447431
TI  - Nosocomial infections due to Acinetobacter baumannii in a neurosurgery ICU.
AB  - Invasive infections caused by Acinetobacter baumannii in a post-operative
      neurosurgery ICU were studied. Sixty one patients admitted during a span of 11
      months were culture positive for acinetobacter species from blood and/or CSF
      samples. They were followed up prospectively for evidence of infection and
      clinical outcome. 40 cases had clinical evidence of infection due to
      acinetobacter species while in 21 patients, the isolation of the organism was
      considered a contaminant. Acinetobacter baumannii was the most common organism
      associated with invasive infections. Respiratory tract was found to be the most
      common primary source of infection in patients with bacteraemia or meningitis.
      The age, sex and pre-operative hospital stay were not significantly different in
      the two groups (p>0.05), while post-operative hospital stay and mortality was
      significantly higher in patients with invasive infection (p<0.05). Acinetobacter
      baumannii was isolated from multiple sites (p<0.05) and repeatedly from the same
      site (p<0.001) in a significantly higher number of patients with invasive
      infections. Mortality was high in the patients infected with Acinetobacter
      baumannii. Even amongst the infected group, the patient shaving meningitis showed
      a higher mortality as compared to the patients having bacteraemia.

PMID- 11447432
TI  - Traumatic subarachnoid haemorrhage: a clinicoradiological and TCD correlation.
AB  - Twenty five consecutive patients with CT proven pure traumatic subarachnoid
      haemorrhage (tSAH) were studied, prospectively over a 6 month period. They
      constituted 2% of all head injuries. Most of the patients (88%) had a mild or
      moderate head injury at the time of admission, with a mean glasgow comma scale
      (GCS) of 10.68. The CT scan findings were divided into 3 grades. Grade 1 - blood
      in hemispheric region only (n=4), grade 2 - blood in basal region only (n=11),
      grade 3 - blood in both hemispheric as well as basal region (n=10). Transcranial
      doppler ultrasound (TCD) velocities were recorded in all patients by insonating
      the middle cerebral artery, internal carotid artery and anterior cerebral artery
      on both sides. All patients were also subjected to digital substraction
      angiography (DSA). All patients with mild head injury had normal TCD velocity
      (<100 cm/sec), while TCD velocities of more than 150 cm/sec were seen only in one
      patient with severe head injury. Patients with severe head injury were found to
      have grade 3 tSAH on CT. No statistically significant correlation was found
      between the CT grade and TCD velocities. Angiographic vasospasm was found in 2
      patients with severe head injury only. 90.2% of patients had good outcome at
      discharge.

PMID- 11447433
TI  - Determination of Ki-67 labeling index in pituitary adenomas using MIB-1
      monoclonal antibody.
AB  - Proliferative activity of 94 pituitary adenomas was assessed by the determination
      of the growth fraction, using MIB-1 monoclonal antibody in formalin fixed,
      paraffin embedded sections. This index was correlated with clinical and
      radiological evidence of invasiveness. The mean Ki-67 labeling index for all
      pituitary adenomas was 0.84% (range 0-17.45%). Hardy stage E tumours (1.44%) had
      a higher Ki-67 labeling index (LI) as compared with Hardy stage 0 tumours
      (0.36%). The difference in the Ki-67 labeling indices between invasive and non
      invasive adenomas was not statistically significant. Hence, the Ki-67 labeling
      index is not a reliable indicator of invasiveness in pituitary adenomas.

PMID- 11447434
TI  - Spinal cord and cauda equina compression in 'DISH'.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) has long been regarded as a
      benign asymptomatic clinical entity with an innocuous clinical course. Precise
      information is lacking in the world literature. Authors report the results of a
      retrospective analysis of 74 cases of DISH. Eleven patients presented with
      progressive spinal cord or cauda equina compression. In nine cases ossified
      posterior longitudinal ligament (OPLL) and in two cases ossified ligamentum
      flavum (OLF) were primarily responsible. Surgically treated patients (eight) had
      far better outcome as compared to the patients managed conservatively, as they
      had refused surgery. 'DISH' is neither a benign condition, nor it always runs a
      innocuous clinical course. In fact, in about 15% of the cases, serious
      neurological manifestations occur, which may require a major neurosurgical
      intervention.

PMID- 11447435
TI  - Selective intra arterial thrombolysis in acute carotid territory stroke.
AB  - The safety and efficacy of selective intraarterial administration of urokinase in
      five male patients, (age range 30 to 65 years, mean 41.2 years), with occlusive
      stroke involving the carotid territory and a normal cranial computed tomography
      scan was evaluated. The time elapsed before treatment ranged from one to 10
      hours. Digital subtraction angiography disclosed distal internal carotid artery
      occlusion in one patient and occlusion of the middle cerebral artery or its
      branches in the others. The urokinase dose ranged from 120,000 to 500,000 units.
      In two patients who received thrombolytic treatment within three hours of the
      onset of symptoms, there was a 100% recanalisation associated with excellent
      neurological recovery. In the remaining three patients, recanalisation rate
      varied from 0 to 50% with partial recovery in two and no recovery in one patient.
      None had a haemorrhagic transformation of the infarct. Although no firm
      conclusions can be drawn because of the small number of patients studied,
      selective intraarterial urokinase therapy appears to be safe and useful in
      patients with carotid territory stroke if undertaken early. Only through a
      multicenter, randomized, controlled trial, enough number of patients can be
      recruited to verify these observations.

PMID- 11447436
TI  - Traumatic middle cerebral artery occlusion: case report and review of
      pathogenesis.
AB  - Traumatic occlusion of the middle cerebral artery (MCA) is a rare cause of
      cerebral infarct. We describe a case of MCA occlusion following blunt head
      trauma. The literature reports some 65 cases of MCA occlusion following non
      penetrating blunt trauma to the head. Arterial dissection, cerebral vasospasm and
      thrombosis have been some of the theories discussed in the pathogenesis of this
      condition. We review the pathogenesis based on anatomy of the M1 segment.

PMID- 11447437
TI  - Trigeminal schwannoma associated with pathological laughter and crying.
AB  - A 46 year old man with trigeminal schwannoma displayed symptoms of ataxia with
      pathological laughter and crying. The tumour developed in the cerebellopontine
      angle, compressing the pontomesencephalic structures backward, extending in the
      posterior parasellar region and Meckel's cave. No recurrence of laughter and
      crying attacks were noted after total removal of the tumour. Theories of
      mechanism of pathological laughter and crying reported in the literature are
      reviewed.

PMID- 11447438
TI  - Giant ocular nerve neurofibroma of the cavernous sinus: a series of 5 cases.
AB  - Five cases of giant cavernous sinus neurofibroma arising from the ocular cranial
      nerves are reported. These patients collected over a period of 5 years consisted
      of 3 males and 2 females with an age range of 9 to 40 years and a mean of 20.6
      years. Clinically, all patients presented with ocular palsies over a long period
      (mean 3.4 years). All of them underwent a frontotemporal craniotomy along with an
      orbito-zygomatic osteotomy and excision of the tumour. In patients with extension
      of the tumour into the orbit, the superior orbital fissure was drilled, the
      tenon's capsule was cut and the intraorbital portion was excised. The management
      of these tumours is discussed and the literature reviewed.

PMID- 11447439
TI  - Congenital intracranial teratoma of the lateral ventricle.
AB  - A case of lateral ventricular teratoma in neonate, where near total excision of
      tumour was done, is being reported with the review of literature.

PMID- 11447440
TI  - An oligo astrocytoma with widespread calcification along axonal fibres.
AB  - A rare case of a young man with a diffusely calcified oligo astrocytoma in right
      parieto occipital region, which spread along the axonal fibres into right
      temporal lobe and to the left parietal lobe is presented. Computed tomography
      (CT) and magnetic resonance imaging (MRI) demonstrated the extent of the lesion.
      The mass was partially resected.

PMID- 11447441
TI  - Bilateral subdural effusion and subcutaneous swelling with normally functioning
      csf shunt.
AB  - We report a child with hydrocephalus due to tuberculous meningitis who developed
      a subcutaneous fluid collection around the ventriculoperitoneal shunt tube entry
      point, after one month of shunting. On investigation, he had decompressed
      ventricles with bilateral fronto parietal subdural hygroma. Bifrontal burr hole
      drainage helped resolution of both subdural effusion and subcutaneous scalp
      swelling. This complication is unique and its pathogenesis has been postulated.

PMID- 11447442
TI  - Cerebral cysticercus granuloma associated with a subdural effusion.
AB  - The association of a solitary cerebral cysticercus granuloma with a subdural
      effusion is being reported. The granuloma and the effusion resolved following
      albendazole therapy. We speculate that the spread of the inflammatory changes
      around the granuloma to the subdural space could have led to the development of
      the subdural effusion.

PMID- 11447443
TI  - Paraneoplastic limbic encephalitis associated with bronchogenic carcinoma: a case
      report.
AB  - Paraneoplastic limbic encephalitis is a rare clinical entity, associated most
      often with the oat cell carcinoma of the lung. Clinically, it presents with
      affective changes in personality, memory loss, confusional state, hallucinations,
      and seizures; with dementia being the common feature as the disorder progresses.
      Response to treatment is disappointingly poor.

PMID- 11447444
TI  - Sciatica due to malignant nerve sheath tumour of sciatic nerve in the thigh.
AB  - Malignant peripheral nerve sheath tumour (MPNST) is a rare malignant neoplasm
      arising from the supportive non-neural component of the peripheral nerves. An
      unusual case of pain and weakness of the foot and calf muscles due to a giant
      MPNST of the sciatic nerve in the posterior compartment of the thigh is
      presented. The patient was already investigated as a case of sciatica due to a
      lumbar disc disease with a negative magnetic resonance imaging and then
      unsuccessfully operated elsewhere twice, with a misdiagnosis of tarsal tunnel
      syndrome. Neurosurgical referral prompted a diagnostic magnetic resonance study
      of the thigh, revealing the lesion, which was completely excised microsurgically
      with total relief in the pain and partial improvement in the weakness and
      sensations in the sole of the foot.

PMID- 11447445
TI  - Massive cerebral infarction as a feature of pituitary apoplexy.
AB  - A patient with pituitary apoplexy is reported who, in addition to the clinical
      features of apoplexy, developed a cerebral infarct secondary to compression of
      the internal carotid artery. The mechanisms of a cerebral infarct associated with
      pituitary apoplexy are discussed.

PMID- 11447446
TI  - Solitary skull metastasis from mucoepidermoid mimicking a parotid tumour.
AB  - Metastatic parotid tumours in the skull are very rare. An interesting case of a
      mucoepidermoid parotid tumour metastasizing to the skull vault is described in a
      patient who had previously been operated for a pituitary adenoma 20 years back
      with no post operative radiotherapy; however, she required hormonal
      supplementation therapy. She underwent an operation for a parotid tumour 7 years
      ago and received postoperative radiotherapy for the parotid tumour away from the
      site of the skull metastases. No local recurrence of the parotid tumour was
      noted. The initial diagnosis was that of a solitary intradiploic meningioma.
      Interesting clinico-radiological findings are presented.

PMID- 11447447
TI  - Chasing hyponatraemia: unusual presentation.
AB  - Two females, in their sixth decade, presented with recurrent episodes of
      headache, vertigo, vomiting and altered sensorium. Both patients had persistent
      hyponatraemia as the only clue. Detailed investigations revealed a pituitary
      aetiology in both. One patient had a pituitary microadenoma while the other had
      an empty sella syndrome. The diagnosis and management is discussed and the
      relevant literature reviewed.

PMID- 11447448
TI  - Primary cerebello-pontine angle malignant melanoma: a case report.
AB  - A rare case of primary malignant melanoma in the cerebello-pontine angle, in a 17
      year old girl is presented. The patient presented with one month history of
      headache, diplopia, facial asymmetry and ataxia. The computerised tomography (CT)
      scan and magnetic resonance imaging (MRI) revealed a large cerebello-pontine
      angle mass with features suggestive of a melanoma. The typical black coloured,
      solid and vascular melanoma was excised completely. Cerebello-pontine angle
      melanoma are extremely rare tumours with dismal long term outcome in majority of
      these cases.

PMID- 11447449
TI  - Primary spinal intradural hydatid cyst--a short report.
AB  - Primary spinal hydatid cysts are uncommon. Among these, intradural presentation
      is very rare. A case of primary spinal intradural hydatid cyst presenting as
      incomplete dorsal cord compression is reported here for its rarity.

PMID- 11447450
TI  - Meningioma associated with contralateral chronic subdural haematoma: a short
      report.
AB  - Two unusual cases of meningiomas associated with opposite chronic subdural
      haematoma are presented.

PMID- 11447451
TI  - Cisternal cysticercosis: a diagnostic problem--a short report.
AB  - We describe a patient in whom a hypodense nonenhancing mass on CT scan in the
      regions of quadrigeminal cistern, and causing obstructive hydrocephalus, was
      initially diagnosed as an epidermoid but subsequent MR evaluation and surgery
      resulted in the diagnosis of a racemose cysticercus cyst.

PMID- 11447452
TI  - Giant orbital and intracranial xanthogranuloma--a short report.
AB  - Xanthogranuloma are known to arise in the paranasal sinus or orbit. They may also
      arise primarily in the brain. Those arising from the sinuses or orbit might
      involve the intracranial cavity to some extent. But an extensive involvement of
      the cranial compartment is very rare. This report describes one such case.

PMID- 11447453
TI  - Posterior fossa dermoid in association with Klippel-Feil syndrome--a short
      report.
AB  - A posterior fossa dermoid cyst in association with the Klippel-Feil syndrome, in
      a 4 year old child is reported. Early diagnosis to prevent complications like
      neural compression, cyst rupture and staphylococcal meningitis justifies
      investigation for posterior fossa dermoids in cases of Klippel-Feil syndrome.
      Their embryological basis is discussed.

PMID- 11447454
TI  - Paradoxical triceps jerk, a neglected localising sign in clinical neurology.

PMID- 11447455
TI  - Diffuse meningeal involvement in tubercular meningitis.

PMID- 11447456
TI  - Beta band seizure pattern.

PMID- 11447457
TI  - Cerebellar syndrome in a case of uncomplicated Plasmodium falciparum malaria.

PMID- 11447458
TI  - Idiopathic late onset cerebellar ataxia in a case of Takayasu's arteritis.

PMID- 11447459
TI  - From the desk of the President of the South African Heart Association.

PMID- 11447460
TI  - Coronary heart disease - any likelihood of benefit from the control of Chlamydia
      pneumoniae?

PMID- 11447461
TI  - Chlamydia pneumoniae and atherosclerosis.

PMID- 11447462
TI  - Histological and ultrastructural findings suggesting an initiating role for
      Chlamydia pneumoniae in the pathogenesis of atherosclerosis.
AB  - AIMS: An association between Chlamydia pneumoniae and atherosclerosis is now well
      established. The finding of C. pneumoniae in atherosclerotic lesions has led to
      the hypothesis that this organism may have an aetiological role in atherogenesis.
      The implications of such a concept are enormous, but to date the pathological
      features of the lesion have not been examined in the light of this new
      hypothesis. This study was designed to determine the pathological basis of the
      association between C.pneumoniae and atherosclerotic lesions. METHODS: The
      pathological features of 50 atherosclerotic lesions from 50 different patients,
      in which C.pneumoniae had been demonstrated by immunocytochemistry and PCR
      techniques, were examined using light and electron microscopy techniques. In 20
      cases the lesions were fatty streaks, 20 were fibro-atheroma lesions, and 10 were
      advanced, complicated lesions. RESULTS: Intimal smooth-muscle cells infected with
      C. pneumoniae exhibit vacuolation, loss of myofilaments, an increase in lipid,
      rupture and fragmentation. Macrophages phagocytose these muscle cell fragments,
      lipid and C. pneumoniae. Large numbers of extracellular C. pneumoniae organisms
      were identified in the central necrotic core, in areas of fibrosis, in areas of
      fragmentation of the internal elastic lamina, and in ceroid bodies. Neither
      pathological changes nor organisms were seen in the endothelium. CONCLUSIONS : C.
      pneumoniae infection of intimal smooth&hypen; muscle cells is accompanied by
      cytoplasmic alterations and damage. The fatty streak appears to be formed by a
      macrophage response to this muscle damage. C. pneumoniae is found in early,
      mature and advanced lesions. This is the first study of the pathology of
      atherosclerosis suggesting that the lesion be interpreted as an infective
      chlamydial granuloma.

PMID- 11447463
TI  - Myocardial infarction associated with Chlamydia pneumoniae.
AB  - A 39-year-old black South African man with no recognised risk factors for
      coronary hart disease (CHD) except hypertension, died of a myocardial infarct
      (MI). The case was unusual because although hypertension is common, MI is rare in
      black South Africans. Serology indicated that the subject had previously had a
      Chlamydia pneumoniae infection. The primary lesion in the left anterior
      descending branch of the coronary artery was a ruptured atherosclerotic plaque in
      which C. pneumoniae was indentified by immunocytochemical, electron microscopic
      and polymerase chain reaction techniques. The organisms were detected in smooth
      muscle cells, foam cells and interstitially, but not in adjacent unaffected
      tissue. C. pneumoniae DNA was also detected in the myocardium of the left
      ventricle in an area of the infarct. It is postulated that debris from the
      ruptured plaque was deposited in the muscle. The observations support the
      association between C. pneumoniae and CHD; for the first time the organism is
      identified in a lesion that ruptured and caused an MI.

PMID- 11447464
TI  - The pulmonary autograft (Ross operation) as aortic valve replacement.

PMID- 11447465
TI  - Diuretics in congestive heart failure which one, what dose, and does it make a
      difference?

PMID- 11447466
TI  - Coronary heart disease risk factors in Indian adolescents the role of diet.
AB  - This study tested the hypothesis that the habitual diet of Indian adolescents
      contributes to coronary heart disease (CHD) risk factors. A random sample of 321
      Indian matriculants aged 16 - 18 years participated. Anthropometric and blood
      pressure measurements were made with standardised methodology. Habitual dietary
      intakes were measured using a validated food frequency questionnaire. Serum
      lipids and lipoproteins and plasma fibrinogen and factor VII coagulant activity
      were determined on samples obtained from fasted subjects. The demographic
      questionnaire results indicated that 20% of the adolescents smoked. Mean serum
      total cholesterol levels of 43% of the non-vegetarian males and 37% of the
      females fell in the low CHD risk category. Mean plasma fibrinogen levels of 2.28 
      2.93 g/1 were higher than those reported for white students, but lower than
      those of black South Africans. These adolescents habitually ate a diet high in
      fat (41.5 - 47.7% of total energy) and low in carbohydrate (44.4 - 48% of total
      energy). The significant relationships observed between nutrient intakes and the
      risk factors for CHD suggest that diet plays an important role in the development
      of CHD in this population. The significant relationships between triglycerides,
      blood pressure, weight, percentage of high-density lipoprotein (HDL) cholesterol
      and fibrinogen further suggest a clustering of risk factors all known to be
      associated with an insulin-resistant state. It is concluded that although a
      possible genetic and dietary interaction of causative risk factors results in the
      high CHD risk of this population, the role of diet in the clustering of risk
      factors in these Indian adolescents should be further examined. It is suggested
      that compliance to a culture-sensitive, low-fat, high-carbohydrate diet could
      possibly lower their risk.

PMID- 11447467
TI  - Management of graft occlusion following aortobifemoral bypass.
AB  - BACKGROUND: There is doubt as to whether operative mortality and subsequent graft
      patency and limb salvage rates support repeated efforts at revascularisation in
      patients with occluded aortobifemoral grafts. STUDY DESIGN: Prospective study of
      hospital patients with aortobifemoral graft occlusion presenting to the Durban
      metropolitan hospitals. The study was designed to assess outcome of
      revascularisation in these patients. METHOD: This is an analysis of 65 patients
      who developed graft occlusion out of a total of 492 aortobifemoral bypasses
      monitored over a 9-year period. Patients were investigated with angiography
      before being subjected to re-operation. They were followed up in the vascular
      clinic. RESULTS: The incidence of graft occlusion in this cohort was 15%. There
      were 11 early occlusions (2.6 days after the procedure) and 54 late occlusions
      (28 months after the procedure). Eight early graft occlusions were managed by
      means of thrombectomy, 1 with additional profundoplasty, and 3 were managed
      conservatively. Late complications were graft occlusion (1), graft sepsis (1) and
      aorto-enteric fistula (1). Late graft occlusions were managed by crossover (18),
      profundoplasty (7), axillo-femoral bypass (5), graft limb reconstruction (5) and
      redo procedures (2); 20 patients were managed conservatively. There was 1
      postoperative death among the patients who experienced early occlusion, and none
      among those with late occlusion. Long term complications included secondary graft
      occlusions (3), graft sepsis (1) and amputations (5). The limb salvage rate was
      63%. CONCLUSION: This study has shown that acceptable results can be achieved
      with surgery for graft occlusion following aortobifemoral bypass and that
      different treatment options are available.

PMID- 11447468
TI  - Clinical significance of internal thoracic artery morphometry and inter-ethnic
      differences.
AB  - The internal thoracic artery (ITA) is used extensively for coronary
      revascularisation. Clinical observations suggest an inter-ethnic difference in
      ITA morphometry between Indians and whites presenting for coronary artery bypass
      surgery. However, accurate morphometric data comparing these ethnic groups were
      not available. This study analyses the morphometry of the left and right ITAs in
      60 cadavers (43 blacks, 9 whites, 8 Indians). The lengths of the arteries were
      measured and the external diameters were recorded at the origin of the 1st, 4th
      and 6th costal cartilages. Significant differences in length and diameter on the
      right and left sides between ethnic groups were demonstrated. In particular,
      these differences were marked between the white and Indian groups. Clinically,
      these differences can be so marked that in some instances the left ITA in Indian
      patients is so small at the distal point of take-down as to be unsuitable for use
      as an arterial conduit. This is one of the reasons that has prompted the use of
      the ITA as a composite graft. Our study appears to be the first to highlight this
      inter-ethnic difference and to support the clinical impression.

PMID- 11447469
TI  - A South African pharmaco-economic analysis of the Acute lnfarction Ramipril
      Efficacy (AIRE) Study.
AB  - OBJECTIVES: Heart failure (HF) is a serious, prevalent health condition in
      industrialised countries where the incidence has been on the increase. The
      economic repercussions are costly, and therefore cost-effective medication is
      important in the overall management of the condition. It has been shown that
      angiotensin-converting enzyme (ACE) inhibitors are clinically effective in the
      management of HF. Ramipril has been shown to reduce mortality and the probability
      of hospitalisation in post-myocardial infarction (MI) patients. Internationally,
      the use of this drug has proved to be cost-effective. The objective of this study
      was to investigate the economic implications of using ramipril in South Africa
      for post-MI patients with HF. METHODOLOGY: An incremental cost-effectiveness
      analysis was performed comparing the use of ramipril and placebo in post-MI
      patients with HF who were receiving standard therapy. The economic impacts
      included drug acquisition costs and savings on hospitalisation; these were
      evaluated based on the clinical benefits of using ramipril in terms of life-years
      gained (LYG). The cost-utility of the use of ramipril was determined to provide
      an incremental cost per quality-adjusted life-year (QALY). Sensitivity analyses
      were performed on the major economic variables; discounting of future costs and
      savings was performed at rates of 0%, 5 % and 10 %. RESULTS: The use of ramipril
      results in an incremental cost/LYG of R16 808 and a total incremental cost per
      patient per month of R107 over 3.8 years. When the quality of life of the
      patients is taken into account, the cost-utility analysis shows an incremental
      cost/QALY of R21 382 for those younger than 65 years of age and R18 029 for those
      older than 65 years. The pharmaco-economic model was robust and consistent when
      tested at the extremes of the major variables, including costs, savings and
      discount rates. CONCLUSION: The results indicate that it is cost-effective to
      administer ramipril in addition to standard therapy for post-MI patients with HF
      in South Africa.

PMID- 11447470
TI  - Right ventricular thrombosis in arrhythmogenic right ventricular dysplasia.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) has recently received increased
      recognition. We report on a clinical case of ARVD and associated right
      ventricular thrombus, an entity reported only in postmortem studies up till now.

PMID- 11447471
TI  - An uncommon cause of pulmonary hypertension.
AB  - A 32-year-old woman presented with severe pulmonary hypertension and cor
      pulmonale in congestive cardiac failure. The diagnosis was established by means
      of positive anti-schistosomal immunoglobulin G (IgG) antibodies and
      ultrasonographic evidence of hepatosplenic schistosomiasis with portal
      hypertension. Extensive investigations revealed no other cause for the pulmonary
      hypertension, providing proof for the diagnosis of pulmonary schistosomiasis. The
      literature reviewed indicates very few cases of this rare complication. The
      pathology in general is reviewed in this report as well as some 'pathogenic'
      mechanisms of this case.

PMID- 11447472
TI  - Thrombo-embolism after cardioversion of atrial fibrillation.

PMID- 11447473
TI  - The endothelins.

PMID- 11447474
TI  - Protection of the heart against ischaemic damage.

PMID- 11447475
TI  - Valvular heart disease associated with systemic lupus erythematosus - the
      Tygerberg Hospital experience.
AB  - BACKGROUND: Valvular heart disease is the most important cardiac manifestation of
      systemic lupus erythematosus (SLE). We performed a study to determine the
      presence of valvular heart disease in our patients with SLE. METHODS: We
      performed clinical, electrocardiographic, transthoracic echocardiographic and
      laboratory evaluations in 24 patients with SLE. The echocardiographic findings
      were compared with those of 10 age- and sex-matched volunteers. RESULTS: None of
      the 24 patients had obvious symptoms of cardiac origin. Valvular abnormalities
      were common. Valvular thickening was the most predominant finding (more than
      50%), followed by mitral valvular regurgitation (12.5%) and pericardial effusions
      (12.5%). Valvular abnormalities were uncommon in the control group. CONCLUSION:
      Valvular heart disease is common in our patient population with SLE, although
      haemodynamically significant valvular dysfunction is rare.

PMID- 11447476
TI  - An explanation of the unusual electrocardiographic findings in a patient with
      pulmonary agenesis and dextrocardia.
AB  - Interpretation of the electrocardiagram (ECG) is extremely helpful in
      distinguishing between the different forms of dextrocardia. The patient in this
      report had agenesis of the right lung and dextroposition; the ECG mimicked mirror
      image dextrocardia, with elements of dextroversion also present.

PMID- 11447477
TI  - Transoesophageal echocardiographic demonstration of mechanism for right-to-left
      shunting across a patent foramen ovale in acquired tricuspid regurgitation.
AB  - This case report describes a patient who presented with left middle cerebral
      artery infarction and was found to have a systolic right-to-left shunt across a
      patent foramen ovale. These features were secondary to severe acquired tricuspid
      regurgitation.

PMID- 11447478
TI  - Use of aspirin in cardiovascular prophylaxis.
AB  - The value of prophylatic low-dose aspirin in patients who have experienced a
      myocardial infarction (MI), stroke or transient ischaemic attack (TIA) has been
      established beyond all reasonable doubt in a number of major overviews of
      randomised controlled trials. The value of aspirin in so-called 'primary
      prevention' is debated, but discussions are based on a misunderstanding. The
      terms 'primary' and 'secondary' relate to past vascular events and the occurrence
      of a prior event is only one factor in the estimation of the risk of a future
      event. Trials have confirmed that patients at high risk, who have not already had
      a clinical event, do benefit from aspirin. The estimation of risk, and the
      balancing of this against the chance of undesirable side-effects from aspirin,
      constitutes a clinical judgement. Although there is only limited evidence from
      trials, it is reasonable to assume that the earlier aspirin is given in
      infarction, the greater the benefit is likely to be. This assumption underlies
      advice from a number of bodies that aspirin should be given by a doctor, nurse or
      paramedic on first contact with a patient experiencing sudden severe chest pain.
      Again, although there is no direct evidence from trials, it would seem reasonable
      to advise patients who have been judged to be at increased risk of infarction to
      carry aspirin tablets and to chew and swallow one or two immediately if they
      experience sudden severe chest pain. Aspirin has a fascinating history. The new
      uses now being suggested, namely in the management of dementia, cancer and other
      conditions, make it likely that it will have an even more fascinating future.

PMID- 11447479
TI  - Diabetes and coronary heart disease.

PMID- 11447480
TI  - Hypertrophic cardiomyopathy repealing tenets in South Africa.
AB  - Hypertrophic cardiomyopathy (HCM), a common primary cardiac disorder with an
      increased risk of sudden death, affects all population groups in South Africa.
      Distinct causal mutations in multiple sarcomeric protein-encoding genes correlate
      with the risk of sudden death. Such genotype/phenotype correlations cannot be
      extrapolated geographically or ethnically, necessitating the generation of South
      African-specific data. We used DNA-based techniques to search for the causal
      mutations in a panel of South African HCM-affected subjects (37 with unequivocal
      HCM, 47 with HCM-like disease). Mutations detected were traced in family members
      and carriers assessed by echocardiography and electrocardiography. Nine different
      HCM-causing mutations (5 unique to South Africa, 3 showing a founder effect) were
      identified in 3 genes in 24 index cases (57% HCM group, 6% HCM-like group). The
      different mutations were associated with variable hypertrophy, independent of the
      risk of sudden death. The disease was generally familial and many at-risk
      mutation carriers did not meet clinical diagnostic criteria for HCM. Rigorous
      diagnosis of index cases facilitates detection of causal mutations, which allows
      for unequivocal DNA-based diagnosis of at-risk family members, regardless of age
      or clinical status. This permits focused patient management, informed
      prognostication and realistic counselling for this insidious disease, as well as
      time and cost savings.

PMID- 11447481
TI  - Complete atrioventricular septal defect.
AB  - Complete atrioventricular septal defect (CAVSD) is known to be associated with
      Down syndrome (DS) and to be a major cause of infantile death in these patients.
      Recently several leading articles reported that complete surgical repair before 6
      months of age is a relatively low-risk procedure leading to a dramatic
      improvement in outcome. Most surgical reviews, however, fail to describe their
      selection criteria and to include patients who die early in infancy or who are
      unfit for surgery for some or other reason. A retrospective descriptive study was
      done of all children with CAVSD treated over a period of 15 years from 1980 to
      1994 at our institution. The aims were to describe the profile of children with
      CAVSD in our population, and to evaluate screening procedures and treatment
      received versus outcome. Thirty-three patients were included in the study, 25
      with DS and 8 without. The basic skills of careful auscultation, interpretation
      of chest radiograph and electrocardiograms (ECGs) are all 100% sensitive in
      alerting the physician to this condition. Careful screening, especially of DS
      babies, is essential to ensure early optimal intervention. Echocardiography is
      the least invasive, most informative investigation to establish a definite
      diagnosis. The Rastelli anatomical classification is highly indicative of
      outcome. Children in the Rastelli C group showed a universally dismal prognosis.
      Digitalis and furosemide are still the mainstay of medical treatment. No
      additional benefit was observed with the limited introduction of angiotensin
      converting enzyme (ACE) inhibitors. Complete repairs were undertaken earlier and
      more frequently in recent years, but limited resources had led to the majority of
      patients not receiving surgery at all. There was insufficient urgency to aim for
      early complete repair, and more than 20% of children died before even being
      considered for surgery. This study is the first in South Africa to describe our
      own patient population and to evaluate local practice. Adequate screening of
      babies (especially those with DS), with early referral for complete repair in the
      first 6 months of life, remains the goal of optimal management.

PMID- 11447482
TI  - Cardiac sarcoidosis &hypen; the value of magnetic resonance imaging.
AB  - This report describes the management of a 40-year-old woman presenting with
      recurrent monomorphic ventricular tachycardias secondary to cardiac sarcoidosis.
      She was managed with a combination of steroids, azathioprine and mexiletine.
      Magnetic resonance imaging proved to be of great help in diagnosing this
      condition as well as in following up the response to therapy. A brief review on
      the management of this condition is presented.

PMID- 11447483
TI  - Renewed interest in centrally acting antihypertensive drugs.
AB  - Classic centrally acting drugs such as clonidine and alpha-methyldopa induce
      peripheral sympatho-inhibition via the stimulation of alpha(2)-adrenoceptors in
      the brainstem. From a haemodynamic point of view this appears to be a useful
      mechanism to lower elevated blood pressure in hypertensives. Although not known
      in full detail, a complex relationship exists between the sympathetic nervous
      system and hypertensive disease; sympathetic inhibition therefore appears to be a
      logical target of antihypertensive drug treatment. Numerous attempts have been
      made to improve the unfavourable side-effect profile of the centrally
      actingalpha(2)-adrenoceptor stimulants. None of these attempts were successful,
      since both the central antihypertensive activity and the major side-effects
      (sedation, dry mouth) are mediated by alpha(2)-adrenoceptors. A new approach in
      this field has been offered by the introduction of centrally acting
      antihypertensives which interact with central imidazoline (I(1))-receptors and
      thus cause peripheral sympatho-inhibition. As such they offer haemodynamic
      benefits similar to those of the classic alpha(2)-adrenoceptor agonists. However,
      it is hoped that their side-effect profile will be more favourable because of
      their much weaker affinity for alpha(2)-adrenoceptors. Moxonidine and rilmenidine
      are the prototypes of centrally acting I(1)-receptor stimulants. The
      antihypertensive activity of these agents is caused by vasodilatation and a
      reduction of peripheral vascular resistance. Left ventricular end-diastolic and
      end-systolic volumes are reduced, whereas heart rate, stroke volume, cardiac
      output and pulmonary artery pressures are largely unchanged. Left ventricular
      hypertrophy (LVH) is reduced in the long term. Both drugs when applied in a once
      daily dosage schedule appear to control hypertension in most patients. Both drugs
      have been compared with representative agents from the major classes of
      antihypertensives in controlled trials and have been found to be equally
      effective with respect to blood pressure control. The incidence and severity of
      side-effects is lower than for clonidine, in particular with respect to sedation.
      A rebound (withdrawal) phenomenon has so far not been reported for moxonidine and
      rilmenidine. In conclusion, I(1)-receptor stimulants appear to offer the
      potential to be developed as centrally acting agents with a better side-effect
      profile than the classic alpha(2)-adrenoceptor stimulants, but with similar
      haemodynamic properties.

PMID- 11447484
TI  - Any hopes of coronary heart disease incidence falling in Western populations?

PMID- 11447485
TI  - Secundum atrial septal defects - a review of 75 patients.
AB  - Secundum atrial septal defect (ASD) is the most common type of ASD within the
      spectrum of congenital cardiac abnormalities in children. In this retrospective
      study the data on 75 patients with a pure secundum ASD were analysed. The
      male/female ratio was 1:1,3. This is less than the reported male / female ratio,
      of 1:2. The symptoms most often found were shortness of breath, cough and
      susceptibility to fatigue. An ejection systolic heart murmur was found in the
      majority of the patients. A fixed split second heart sound was only found in 49%
      of patients. This could have been the result of incomplete documentation,
      inexperienced clinicians, a fast heart rate or the fact that a split second heart
      sound is not always present in patients with ASDs. On the chest radiograph the
      majority of patients presented with right ventricular enlargement, right atrial
      enlargement and increased pulmonary blood flow. A relatively unexpected finding
      on echocardiography was left atrial enlargement. This is usually caused by volume
      overload in the presence of large ASDs. Another unexpected finding was the high
      number of left QRS-axis deviations (10%) and indeterminate QRS-axis deviations,
      left rotation (7%) present on the electrocardiogram. This finding is much higher
      than the reported 3.8% of left QRS-axis deviation present in patients with
      secundum ASDs. The only explanation for this phenomenon is that during the
      embryological development of the atrial septum, not only does a secundum ASD
      develop, but the endocardial cushion becomes involved, giving rise to abnormal
      conductive pathways.

PMID- 11447486
TI  - Opioids and protection against myocardial ischaemic damage.

PMID- 11447487
TI  - Opioid receptor stimulation acts as mediator of protection in ischaemic
      preconditioning.
AB  - Involvement of the opioid receptors in preconditioning-induced protection has
      recently been described. The aims of this study were to establish whether: (i)
      opioid receptor stimulation acts as a trigger ( during the preconditioning
      protocol) or as a mediator ( during sustained ischaemia) of cardioprotection
      using either morphine or [D-ala(2), D-leu(5)] enkephalin (DADLE), a synthetic
      delta-opioid receptor agonist; ( ii) the beneficial effects of DADLE are protein
      kinase C ( PKC) -mediated; and (iii) inhibitory 'cross-talk' occurs between the
      beta-adrenergic and phosphatidylinositol pathways activated by release of
      endogenous catecholamines and opioids respectively during sustained ischaemia.
      The isolated, perfused working rat heart, subjected to 25 minutes' global
      ischaemia and 30 minutes' reperfusion, was used as the experimental model. The
      results showed that delta-opioid receptor stimulation with DADLE (10(-8) M), when
      administered for 3 x 5 minutes, had no effect, while when given 10 minutes before
      sustained ischaemia the drug significantly improved functional recovery during
      reperfusion. This indicates that opioid receptor stimulation acts as a mediator
      rather than a trigger in the protection elicited. Morphine ( 3 x 10(-7)) when
      administered in the same manner was without effect. Opioid receptor stimulation
      caused a marked reduction in the beta -adrenergic response to isoproterenol,
      indicating inhibitory cross-talk between the phosphatidyl-inositol and beta
      adrenergic signal transduction pathways. However, reduction of the beta
      adrenergic response to ischaemia does not appear to be the mechanism of opioid
      induced protection, as indicated by 3',5' -cyclic adenosine monophosphate (cAMP)
      levels at the end of 25 minutes' global ischaemia. Opioid receptor-mediated
      protection against ischaemic damage is PKC-dependent, since DADLE-induced
      protection could be abolished by the inhibitor chelerythrine.

PMID- 11447488
TI  - Background and early results of a modified left atrial radiofrequency procedure
      concomitant with cardiac surgery.
AB  - With the introduction of the maze operation Cox was able to show that the
      surgical treatment of atrial fibrillation (AF) is feasible. However, the maze
      operation remains surgically demanding and time-consuming as it requires multiple
      incisions in both atria. This has led to the development of various
      modifications. With new ablative technology and the acceptable results of an
      exclusively left atrial maze procedure in combination with mitral valve surgery,
      it has become possible to simplify the maze operation radically. Thirty-one
      patients ( mean age 62.3 years) with chronic or intermittent AF underwent a
      modified radiofrequency procedure in combination with some other cardiac surgical
      operation. Mitral valve disease coexisted in 17 patients, aortic valve disease in
      9, coronary heart disease in 4 patients and 1 had an atrial septal defect (ASD).
      After left atriotomy and with the use of the Thermaline radiofrequency ablator
      probe, bilateral pulmonary vein isolation was carried out. An additional ablation
      line was directed from the left pulmonary veins to the posterior mitral valve
      annulus, and finally the left atrial appendage was resected. The complete
      procedure added an average of only 18.2 minutes to the operation. In the early
      postoperative course AF or atrial flutter recurred in 12 patients but at
      discharge only 8 patients (24%) still had an arrhythmia. We concentrated on the
      first 26 patients of our series who had received a follow-up examination 3 months
      postoperatively. At discharge 18 of the 26 patients were in sinus rhythm (69,2%),
      and at 3 months after surgery 23 of 26 patients were in sinus rhythm (88.5%),
      with recovery of atrial contraction confirmed echocardiographically. Only 4
      patients still required medication for arrhythmias. The modified radiofrequency
      ablation procedure of the left atrium proved to be simple to perform, quick and
      reliable. It offers the possibility of a surgical cure for AF when performed
      together with another cardiac operation, and the early results indicate a high
      rate of success for this simple procedure.

PMID- 11447490
TI  - Twelve-lead electrocardiography in tuberculous pericarditis.
AB  - OBJECTIVES: This study is part of an ongoing initiative started in 1995 to
      investigate the therapeutic efficacy of adjuvant corticosteroids in the
      management of tuberculosis (TB) pericarditis. In this retrospective, descriptive
      study we describe the changes found on the 12-lead electrocardiogram (ECG) in
      patients with TB pericarditis, with and without cardiac tamponade. We determined
      the diagnostic accuracy of ECG parameters for cardiac tamponade. METHODS: All
      patients referred to our department with echocardiographically confirmed large
      pericardial effusions underwent a thorough clinical assessment followed by
      pericardiocentesis and drainage using an indwelling pigtail catheter. The amount
      of drained effusion was measured, and fluid was sent for diagnostic assessment.
      Patients were grouped into those with or without cardiac tamponade. The following
      ECG parameters were assessed: rate, rhythm, microvoltage, electrical alternans,
      PR segment and ST segment abnormalities. RESULTS: Of the 157 patients assessed,
      88 were diagnosed with TB pericarditis All had abnormal ECGs and 83% had changes
      of chronic pericarditis. Microvoltage in the extremity and/or precordial leads
      correlated with the presence of large effusions (> 750 ml). None of the studied
      parameters correlated with the presence of cardiac tamponade. CONCLUSIONS: Twelve
      lead ECG is of supportive but not diagnostic value in cardiac tamponade. The
      presence of microvoltage suggests the presence of a large effusion. The absence
      of microvoltage makes the presence of cardiac tamponade unlikely.

PMID- 11447491
TI  - Current role of thrombolytic therapy in the management of left-sided prosthetic
      valve obstruction.

PMID- 11447492
TI  - Association between Chlamydia pneumoniae and atherosclerotic lesions.
AB  - There can no longer be any doubt that viable Chlamydia pneumoniae organisms are
      present in atherosclerotic lesions. Indeed, the endovascular presence of C.
      pneumoniae in coronary artery disease (CAD) is common. The fact that this lesion,
      which is the major cause of stroke, coronary heart disease ( CHD), peripheral
      vascular disease and aortic aneurysm, can no longer be regarded as sterile has
      prompted a good deal of study and speculation. Atherosclerotic lesions have been
      studied in detail, but until recently histological descriptions of the lesion
      have not included C. pneumoniae organisms. Reviews and analysis of the literature
      confirm the association between C. pneumoniae and atherosclerotic lesions and
      CHD. The possibility that C. pneumoniae plays a causal or contributory role in
      the development of atherosclerotic lesions has been debated. It is of major
      importance as there is already evidence that antibiotic therapy may be of
      clinical benefit in patients with CHD. Large clinical trials using antichlamydial
      agents have been embarked upon which may provide further evidence of a causal
      role for C. pneumoniae. The underlying mechanism of how C. pneumoniae contributes
      to lesions and the effect of antibiotic therapy on lesions remain unknown. The
      association between C. pneumoniae and atherosclerosis is reviewed. Particular
      attention is paid to the lesion itself and the presence of C. pneumoniae.
      Potential areas of study that may contribute to this rapidly expanding area of
      research is explored.

PMID- 11447493
TI  - Congenital aneurysm of the left main coronary artery with fistulous communication
      to the right atrium and coronary 'steal' phenomenon.
AB  - We describe a unique case of a left coronary arteriovenous fistula arising from
      an extremely short and aneurysmal left main coronary artery and selectively
      affecting the blood flow in the circumflex coronary artery. The relevant
      diagnostic contributions of two-dimensional echocardiography, colour flow
      Doppler, cardiolite stress testing and coronary angiography are discussed. The
      haemodynamic features of this anomaly are reviewed.

PMID- 11447494
TI  - Primary aldosteronism--a new perspective in South Africa.

PMID- 11447495
TI  - Association study of eight candidate genes with renin status in mild-to-moderate
      hypertension in patients of African ancestry.
AB  - AIM: We evaluated whether any one variant of genes that encode for substances
      that could modulate renin-angiotensin-aldosterone (RAA) system activity can
      account for a substantial proportion of the variability of plasma RAA system
      profiles in black South African hypertensives (HTs). METHODS: Plasma renin
      activity (PRA) and aldosterone concentrations (ALD) were determined in 59 black
      subjects with mild-to-moderate HT off therapy on an ad libitum diet. Patients
      were genotyped for the angiotensin-converting enzyme (ACE) gene
      insertion/deletion, angiotensinogen (AGT) gene M235T, A-20C and G-6A, aldosterone
      synthase (CYP11B2) gene C-344T, G protein beta3-subunit (GNB3) gene C825T, G(s)
      protein gene C131T, atrial natriuretic peptide (ANP) gene exon 3 stop condon and
      intron 2, alpha-adducin gene Gly460Trp, and epithelial Na(+) channel (eNa(+) (c))
      gene T594M polymorphisms. RESULTS: Risk genotype frequencies for the G(s) (7%),
      ANP intron 2 (0%), and eNa(+)(c)(7%) variants were too low for each to account
      for a substantial portion of the variability of plasma RAA profiles in the group
      studied. Moreover, assuming either recessive or dominant inheritance models,
      neither ACE, AGT, GNB3, CYP11B2, ANP exon 3 nor alpha-adducin polymorphisms were
      significantly associated with the variance of PRA, ALD or ALD/PRA. CONCLUSIONS:
      These results do not support a substantial individual role for the gene
      candidates studied in contributing to plasma RAA system profiles in black South
      African HTs. However, a potential small role for some loci may exist, and
      epistasis or genotype-phenotype interactions as well as alternative inheritance
      models and variants still need to be evaluated.

PMID- 11447496
TI  - Blood pressure patterns in pregnant patients on oral ketanserin.
AB  - BACKGROUND: Ketanserin, a selective serotonin-2 receptor antagonist, decreases
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) in non-pregnant
      patients with hypertension, but not in normotensive subjects. Its effect on
      longitudinal blood pressure (BP) patterns in pregnant women has not been
      documented. OBJECTIVES: To assess how ketanserin, given orally, influences
      maternal BP during pregnancy. DESIGN: A double-blind randomised controlled trial
      where patients with DBP > or =80 mmHg between 12 and 20 weeks' gestation received
      either ketanserin or placebo. SETTING: Tygerberg Hospital, a tertiary referral
      unit in the Western Cape. SUBJECTS: One hundred and two patients who received
      their study drug for at least 140 days during pregnancy. Patients requiring
      additional antihypertensive medication were excluded from the analysis. OUTCOME
      MEASURES: Changes in SBP and DBP in relation to gestational age and days since
      entering the study. RESULTS: The mean DBP over the total period was significantly
      lower in the ketanserin group (77 +/- 8.7 mmHg v. 80.8 +/- 9.1 mmHg). The decline
      in DBP was 9.2 mmHg in the ketanserin group and 5.3 mmHg in the placebo group.
      These differences were detected from within 7 days of therapy and persisted for
      most of the pregnancy. The mean SBP did not differ at any stage, although the
      mean fall in SBP was significantly greater in the ketanserin group (8.6 +/- 16.7
      v. 4.1 +/- 17.1 mmHg). CONCLUSIONS: Ketanserin decreased DBP during pregnancy
      significantly more than placebo.

PMID- 11447497
TI  - Evaluation of the rennin-angiotensin-aldosterone system in hypertensive Ivoirian
      subjects--preliminary results.
AB  - Experimental data on the renin-angiotensin-aldosterone system in black Africans
      are very limited. In this study we set up our own values (plasma renin and
      aldosterone) in a group of normotensive Ivoirian male and female (N = 43)
      subjects and compared our results with those published for the white population.
      The values were approximately the same. A parallel study was carried out in a
      black population (N = 48 men and women) consulting a doctor for the first time
      for hypertension in different regions of Cote d'Ivoire. The mean values of plasma
      renin and aldosterone were significantly higher (P < 0.05) in the hypertensive
      compared with the control group.

PMID- 11447498
TI  - The limits of antihypertensive therapy--lessons from Third World to First.
AB  - A rapidly developing 'second-wave epidemic' of cardiovascular disease is flowing
      through developing countries and the former socialist republics. It is now
      evident from World Health Organisation data that coronary heart disease and
      cerebrovascular disease are increasing so rapidly that they will rank as numbers
      1 and 5 respectively as causes of global burden of disease by the year 2020. In
      spite of the current low prevalence of hypertension in some countries, the total
      number of hypertensive subjects in the developing world is high, and a cost
      analysis of possible antihypertensive drug treatment indicates that developing
      countries cannot afford the same treatment as developed countries. In the USA
      only 20% of cases of hypertension are adequately controlled (blood pressure <
      140/90 mmHg), and in the developing world the figure falls to 5 - 10%. Black
      hypertensives have varying responses to antihypertensive therapy. They respond
      well to thiazide diuretics, calcium channel blockers, vasodilators such as alpha
      blockers, hydrazine and reserpine, and poorly to beta-blockers, angiotensin
      converting enzyme (ACE) inhibitors and angiotensin II-receptor antagonists unless
      these drugs are combined with a diuretic. A comprehensive cardiovascular disease
      (CVD) programme is necessary. There are social, economic and cultural factors
      that impair control of hypertension in developing countries. Hypertension control
      should ideally be the initial component of an integrated CVD control programme
      that needs to be implemented in developing countries. Primary prevention through
      a population-based lifestyle-linked programme, as well as cost-effective methods
      of detection and management, are synergistically linked. The existing health care
      infrastructure needs to be orientated to meet the emerging challenge of CVD,
      while empowering the community through health education.

PMID- 11447499
TI  - Current concepts in the treatment of hypertension.
AB  - In spite of the effective drug therapy available for hypertensive patients in
      general, economic and social considerations continue to influence the low rate of
      detection, treatment and control of hypertension in the population of the
      developing world. The Joint National Committee on the Detection, Evaluation and
      Treatment of High Blood Pressure stated that in 1993 age-adjusted stroke rates
      rose slightly and that the age-adjusted rate of decline for coronary heart
      disease appeared to be levelling. Furthermore, rates for the incidence of end
      stage renal disease increased, with hypertension the second most common cause.
      The Report also stated that hypertension control rates did not improve (National
      Health and Nutrition Examination Survey, NHANES III, Phase 1) from 1991 to 1994,
      and there were only 27% on control. These disturbing trends support the need to
      enhance public and professional education and to translate the results of
      research into improved health.

PMID- 11447500
TI  - Will the incidence of coronary heart disease fall in Western populations?

PMID- 11447501
TI  - Molecular recognition within the membrane milieu: implications for the structure
      and function of membrane Pproteins.

PMID- 11447502
TI  - Changes in sodium or glucose filtration rate modulate expression of glucose
      transporters in renal proximal tubular cells of rat.
AB  - Renal glucose reabsorption is mediated by luminal sodium-glucose cotransporters
      (SGLTs) and basolateral facilitative glucose transporters (GLUTs). The modulators
      of these transporters are not known, and their substrates glucose and Na+ are
      potential candidates. In this study we examined the role of glucose and Na+
      filtration rate on gene expression of glucose transporters in renal proximal
      tubule. SGLT1, SGLT2, GLUT1 and GLUT2 mRNAs were assessed by Northern blotting;
      and GLUT1 and GLUT2 proteins were assessed by Western blotting. Renal cortex and
      medulla samples from control rats (C), diabetic rats (D) with glycosuria, and
      insulin-resistant 15-month old rats (I) without glycosuria; and from normal (NS),
      low (LS), and high (HS) Na+-diet fed rats were studied. Compared to C and I rats,
      D rats increased (P < 0.05) gene expression of SGLT2 by approximately 36%, SGLT1
      by approximately 20%, and GLUT2 by approximately 100%, and reduced (P < 0.05)
      gene expression of GLUT1 by more than 50%. Compared to NS rats, HS rats increased
      (P < 0.05) SGLT2, GLUT2, and GLUT1 expression by approximately 100%, with no
      change in SGLT1 mRNA expression, and LS rats increased (P < 0.05) GLUT1 gene
      expression by approximately 150%, with no changes in other transporters. In
      summary, the results showed that changes in glucose or Na+ filtrated rate
      modulate the glucose transporters gene expression in epithelial cells of the
      renal proximal tubule.

PMID- 11447503
TI  - Calcium-sensitive nonselective cation channel identified in the epithelial cells
      isolated from the endolymphatic sac of guinea pigs.
AB  - We identified a Ca2+-sensitive cation channel in acutely dissociated epithelial
      cells from the endolymphatic sac (ES) of guinea pigs using the patch-clamp
      technique. Single-channel recordings showed that the cation channel had a
      conductance of 24.0 +/- 1.3 pS (n = 8) in our standard solution. The relative
      ionic permeability of the channel was in the order K+ = Na+ > Ca2+ >> Cl-. This
      channel was weakly voltage-dependent but was strongly activated by Ca2+ on the
      cytosolic side at a concentration of around 1 mm in inside-out excised patches.
      With cell-attached patches, however, the channel was activated by much lower Ca2+
      concentrations. Treatment of the cells, under cell-attached configuration, with
      ionomycin (10 microm), carbonyl cyanide 3-chlorophenylhydrazone (CCCP, 20
      microm), or ATP (1 mm), which increased intracellular Ca2+ concentration
      ([Ca2+]i), activated the channel at an estimated [Ca2+]i from 0.6 microm to 10
      microm. It is suggested that some activators of the channel were deteriorated or
      washed out during the formation of excised patches. Based on this Ca2+
      sensitivity, we speculated that the channel contributes to the regulation of
      ionic balance and volume of the ES by absorbing Na+ under certain pathological
      conditions that will increase [Ca2+]i. This is the first report of single-channel
      recordings in endolymphatic sac epithelial cells.

PMID- 11447504
TI  - Characterization of NA+/H+ exchanger isoform (NHE1, NH32 and NHE3) expression in
      prairie dog gallbladder.
AB  - Gallbladder Na+ absorption is linked to gallstone formation in prairie dogs.
      Na+/H+ exchange (NHE) is one of the major Na+ absorptive pathways in gallbladder.
      In this study, we measured gallbladder Na+/H+ exchange and characterized the NHE
      isoforms expressed in prairie dogs. Na+/H+ exchange activity was assessed by
      measuring amiloride-inhibitable transepithelial Na+ flux and apical 22Na+ uptake
      using dimethylamiloride (DMA). HOE-694 was used to determine NHE2 and NHE3
      contributions. Basal JNams was higher than JNasm with JNanet absorption. Mucosal
      DMA inhibited transepithelial Na+ flux in a dose-dependent fashion, causing JNams
      equal to JNasm and blocking JNanet absorption at 100 microm. Basal 22Na+ uptake
      rate was 10.9 +/- 1.0 micromol. cm-2. hr-1 which was inhibited by approximately
      43% by mucosal DMA and approximately 30% by mucosal HOE-694 at 100 microm. RT-PCR
      and Northern blot analysis demonstrated expression of mRNAs encoding NHE1, NHE2
      and NHE3 in the gallbladder. Expression of NHE1, NHE2 and NHE3 polypeptides was
      confirmed using isoform-specific anti-NHE antibodies. These data suggest that
      Na+/H+ exchange accounts for a substantial fraction of gallbladder apical Na+
      entry and most of net Na+ absorption in prairie dogs. The NHE2 and NHE3 isoforms,
      but not NHE1, are involved in gallbladder apical Na+ uptake and transepithelial
      Na+ absorption.

PMID- 11447505
TI  - Tween-20 activates and solubilizes the mitochondrial membrane-bound, calmodulin
      dependent NAD+ finase of Avena sativa L.
AB  - Among different treatments assayed, a mix of a nonionic detergent (5% Tween-20)
      with 0.5 m NaCl was found to solubilize a large part of the calmodulin-dependent
      NAD+ kinase bound to the inner mitochondrial membrane. It also stimulated its
      activity by increasing 7 times the maximal velocity. Activity stimulation was
      also observed with phosphatidylcholine, phosphatidylethanolamine and with
      reductants (HSO3 and DTT). This solubilized NAD+ kinase and the calmodulin
      dependent cytosoluble isoform displayed distinct molecular masses, as well as
      different kinetic parameters. We propose that solubilization of membrane-bound
      NAD+ kinase could occur in vivo in Avena sativa and could generate a soluble
      isoform.

PMID- 11447506
TI  - Study of the properties of a channel-forming protein of the cell wall of the gram
      positive bacterium Mycobacterium phlei.
AB  - The gram-positive bacterium Mycobacterium phlei was treated with detergents.
      Reconstitution experiments using lipid bilayers suggested that the detergent
      extracts contain a channel forming protein. The protein was purified to
      homogeneity by preparative SDS-PAGE and identified as a protein with an apparent
      molecular mass of about 135 kDa. The channel-forming unit dissociated into
      subunits with a molecular mass of about 22 kDa when it was boiled in 80%
      dimethylsulfoxid (DMSO). The channel has on average a single channel conductance
      of 4.5 nS in 1 m KCl and is highly voltage-dependent in an asymmetric fashion
      when the protein is added to only one side of the membrane. Zero-current membrane
      potential measurements with different salts implied that the channel is highly
      cation-selective because of negative point charges in or near the channel mouth.
      Analysis of the single-channel conductance as a function of the hydrated cation
      radii using the Renkin correction factor and the effect of the negative point
      charges on the single-channel conductance suggest that the diameter of the cell
      wall channel is about 1.8 to 2.0 nm. The channel properties were compared with
      those of other members of the mycolata and suggest that these channels share
      common features. Southern blots demonstrated that the chromosome of M. phlei and
      other mycolata tested contain homologous sequences to mspA (gene of the cell wall
      porin of Mycobacterium smegmatis).

PMID- 11447507
TI  - Risk factors for lack of asthma self-management knowledge among ED patients not
      on inhaled steroids.
AB  - The study objective was to estimate the level of asthma knowledge and self
      management skills among asthmatic patients who are not on inhaled corticosteroids
      and who present with acute asthma to the emergency department (ED). The design
      was to interview of patients by telephone at 90 to 100 days after enrollment in
      the Fourth Multicenter Airways Research Collaboration (MARC-4), a randomized
      trial comparing inhaled fluticasone versus placebo in addition to standard post
      ED therapy. The setting was a multicenter trial involving 41 US urban EDs.
      Persons aged 12 to 54, not on inhaled steroids, who presented to the ED with
      acute asthma were studied. Of the 617 patients enrolled on MARC-4 405 (66%) were
      contacted. Mean (+/-SD) age was 30 (+/-11); 54% were women; acute asthma severity
      was 44% moderate and 56% severe; and 9% had prior intubation. Twenty percent (95%
      CI 16%-24%) responded that asthma could not be monitored and 40% (95% CI 35%-44%)
      scored low on a hypothetical acute asthma attack scenario. Predictors for lack of
      asthma knowledge and self-management skills were: less than a high school
      education; current smoking; lower median household income; and no history of
      steroid use. These data suggest that many ED patients with asthma have poor
      knowledge of asthma monitoring and poor self-management skills and that a "high
      risk" group is also identifiable. Efforts to design and implement an ED-based
      educational program should be tailored to better meet the needs of this high risk
      group.

PMID- 11447508
TI  - Comparison of quality and cost-effectiveness in the evaluation of symptomatic
      cholelithiasis with different approaches to ultrasound availability in the ED.
AB  - Ultrasound is the imaging study of choice for the detection of gallstones, but
      ultrasound through medical imaging departments (MI Sono) is not readily available
      on an immediate basis in many emergency departments (EDs). Several studies have
      shown that emergency physicians can perform ultrasound themselves (ED Sono) to
      rule out gallstones with acceptable accuracy after relatively brief training
      periods, but there have been no studies to date specifically addressing the
      effect of ED Sono of the gallbladder on quality and cost-effectiveness in the ED.
      In this study, we investigated measures of quality and cost-effectiveness in
      evaluating patients with suspected symptomatic cholelithiasis during three
      different years with distinctly different approaches to ultrasound availability.
      The study retrospectively identified a total of 418 patients who were admitted
      for cholecystectomy or for a complication of cholelithiasis within 6 months of an
      ED visit for possible biliary colic. The percentage of patients who had
      gallstones documented at the first ED visit improved from 28% in 1993, when there
      was limited availability of ultrasound through the Medical Imaging Department (MI
      Sono), to 56% in 1995, when MI Sono was readily available, to 70% in 1997, when
      both MI Sono and ED Sono were readily available (P <.001). There were also
      significant differences over the 3 years in the mean number of days from the
      first ED visit to documentation of gallstones (19.7 in 1993, 10.7 in 1995, 7.4 in
      1997, P <.001); the mean number of return visits for possible biliary colic
      before documentation of gallstones (1.67 in 1993, 1.24 in 1995, and 1.25 in 1997,
      P <.001); and the incidence of complications of cholelithiasis in the interval
      between the first ED visit for possible biliary colic and the date of
      documentation of cholelithiasis (6.8% in 1993, 5.9% in 1995, 1.5% in 1997, P
      =.049). The number of MI Sonos ordered by emergency physicians per case of
      symptomatic cholelithiasis identified increased from 1.7 in 1993 to 2.5 in 1995
      and dropped back to 1.7 in 1997, when 4.2 ED Sonos per study case were also done.
      The cost of ED Sonos was more than offset by savings in avoiding calling in
      ultrasound technicians after regular Medical Imaging Department hours. The
      indeterminate rate for ED Sonos was 18%. Excluding indeterminates, the
      sensitivity of ED Sono for detection of gallstones was 88.6% (95% CI 83.1-92.8%),
      the specificity 98.2% (95% CI 96.0-99.3%), and the accuracy 94.8% (95% CI 92.5
      96.5%). We conclude that greater availability of MI Sono in the ED was associated
      with improved quality in the evaluation of patients with suspected symptomatic
      cholelithiasis but also with increased ultrasound costs. The availability of ED
      Sono in addition to readily available MI Sono was associated with further
      improved quality and decreased costs. The indeterminate rate for ED Sono was
      relatively high, but excluding indeterminates, the accuracy of ED Sono was
      comparable with published reports of MI Sono.

PMID- 11447509
TI  - Rate and prediction of infection in children with diabetic ketoacidosis.
AB  - The purpose of this retrospective cohort study was to determine the rate and
      prediction of infection in children, < or = 21 years, with diabetic ketoacidosis
      (DKA). Over a 6-year period, 247 admissions were identified. There were 171 (69%)
      with no infection, 44 (17.8%) with presumed viral infection, and 32 (12.9%) with
      bacterial infection. The mean WBC for all patients was 17,519 ( +/- 9,582). 118
      (50%) had leukocytosis as defined by a WBC > or = 15,000/mm3. WBC, differential,
      leukocytosis, as well as sex, temperature and new onset diabetes, were not
      significant predictors (P > .05) of bacterial infection. Bacterial infections
      were more common in children < or = 3 years of age (P = .03). There was a
      significant correlation of WBC with both pH (r = -0.59, P < .001) and bicarbonate
      (r = -0.43, P < .001). In conclusion, most children in DKA have no evidence of
      infection. Leukocytosis is common but most likely reflects the severity of DKA
      rather than the presence of infection.

PMID- 11447510
TI  - Empiric treatment of gonorrhea and chlamydia in the ED.
AB  - A retrospective study was conducted on female patients who were screened for
      Chlamydia trachomatis and Neisseria gonorrhea. The purpose of the study was to
      determine if any factors predict empiric therapy at the index visit. Of 911
      patients enrolled in the study, 100 were found to have positive DNA screens and
      54 were given empiric therapy. A logistic regression was used to test the ability
      of age, ethnicity, DNA probe result and provider type (physician or midlevel
      provider), to predict empiric treatment. DNA probe result and provider type were
      the only 2 factors that were found to predict empiric therapy. A subsequent
      analysis using a Cochran-Mantel-Hanszel test to control for DNA probe result
      revealed that the provider type remained the only variable that predicted empiric
      treatment.

PMID- 11447511
TI  - Effect of previous experience of a hurricane on preparedness for future
      hurricanes.
AB  - The purpose of this study was to examine the hypothesis that having experienced a
      major hurricane will promote better preparedness for future ones. A survey was
      conducted in November 1999 at Miami children's Hospital. No statistical
      differences were found between the population that was present in Dade County
      during hurricane Andrew and the one that was not; in regard of the possession of
      a generator at home, the obtaining of material to secure their home, the presence
      of hurricane shutters, the willingness to evacuate their home in case of advise.
      Only 37% of the families that experienced hurricane Andrew would go to a shelter
      versus 49% for the families that did not ( P<.05). It was concluded that we can
      safely reject the hypothesis that having experienced a major hurricane will
      promote better preparedness for future ones. Those who experienced hurricane
      Andrew were less willing to go to a shelter compared with the group that did not.

PMID- 11447512
TI  - Implementation of standing field treatment protocols in an urban EMS system.
AB  - The objective was to describe our experience with implementation of standing
      field treatment protocols (SFTP) in a large, urban EMS system. A prospective,
      consecutive observational study examining the first 21 days of implementation of
      SFTPs in the City of Los Angeles, California. SFTPs were developed for 7 medical
      chief complaints and all major trauma patients. There were 13,586 EMS incidents,
      of which 4,037 (30%) received ALS treatment. SFTPs were used on 2,177 of these
      incidents, representing 54% of all ALS runs and 16% of all EMS incidents. The
      most frequently used SFTPs were for altered level of consciousness (29%), and
      chest pain (25%). The most common errors found were failure to document
      reassessment of the patient after each medication administration (45% fallout
      rate), and failure to document and attach a copy of the ECG to the EMS report
      (40%). The mean fallout rate for failure to establish or attempt IV access,
      administer oxygen, or provide cardiac monitoring was 7%. Out of 1,450 incidents
      with outcome data provided by the receiving hospitals, only 3 cases (2%) involved
      incorrect treatment, with an additional 2 involving the unnecessary use of
      lidocaine. None of these instances resulted in adverse effects or complications.
      SFTPs were integrated into a large EMS system with few procedural errors or
      adverse outcomes.

PMID- 11447513
TI  - Operative versus nonoperative management of blunt abdominal trauma: Role of
      ultrasound-measured intraperitoneal fluid levels.
AB  - This study's objective was to analyze whether the quantity of free
      intraperitoneal fluid on ultrasonography, alone or in combination with unstable
      vital signs, is sensitive in determining the need for laparotomy in patients
      presenting with blunt trauma. Adult patients who presented with blunt abdominal
      trauma to 2 level I trauma centers were enrolled. Combined intraperitoneal fluid
      levels (anechoic stripe) of 5 intraperitoneal areas were measured and defined as
      small (< 1.0 cm), moderate (> 1.0 cm, < 3.0 cm), or large (> 3.0 cm). Unstable
      vital signs were defined as pulse > 100 bpm or systolic blood pressure < 90 mmHg.
      Exploratory laparotomy or computed tomography scan confirmed hemoperitoneum. Of
      270 patients entered into the study, ultrasound detected free intraperitoneal
      fluid in 33 patients. Of the 18 patients with a large fluid accumulation, 16
      underwent exploratory laparotomy (89% sensitivity), and all 8 patients with
      unstable vital signs underwent exploratory laparotomy (100% sensitivity). Of the
      10 patients with a moderate fluid accumulation, 6 underwent exploratory
      laparotomy (60% sensitivity), and 4 of the 6 patients with unstable vital signs
      underwent exploratory laparotomy (67% sensitivity). A large intraperitoneal fluid
      accumulation on ultrasonography in combination with unstable vital signs, is
      sensitive for determining the need for exploratory laparotomy in patients
      presenting with blunt trauma.

PMID- 11447514
TI  - Influence of coconut water on hemostasis.
AB  - Coconut water (CNW) can be used as short-term intravenous hydration and
      resuscitation fluid. We investigated the influence of coconut water on plasma
      coagulation in vitro. Either CNW or physiological saline (PS) was added to
      citrated plasma of 8 healthy volunteers. Coagulation capability of diluted plasma
      was evaluated by thrombelastography (TEG). Replacement of up to 50 % of citrated
      plasma by CNW or PS did not influence initiation of coagulation as indicated by
      split point and reaction time, respectively. Strength of fibrin clot as expressed
      by maximum amplitude (MA) of TEG recording dose dependently declined in both
      groups. Replacing 50 % of citrated plasma by CNW or PS reduced MA by 39% and 32%,
      respectively. The influence of coconut water on hemostasis as assessed by TEG
      does not differ from the effect caused by an identical volume of PS.

PMID- 11447515
TI  - Constipation as a cause of scrotal pain in children.
AB  - Six boys with scrotal pain and constipation were seen at our hospital within the
      past 5 years. All boys had no clinical findings of structural or infectious
      derangements, and experienced relief of testicular symptoms after evacuation of
      the fecal mass. The association between constipation and scrotal pain has not
      been previously reported, and may represent direct neural stimulation or chronic
      inflammation of testicular structures in patients with dysfunctional voiding.
      Recognition of the association between constipation and subacute or chronic
      scrotal pain can guide the clinician towards appropriate therapy for these
      patients.

PMID- 11447516
TI  - Inappropriate fosphenytoin use in the ED.
AB  - The objective of the study was to evaluate how often intravenous (IV)
      fosphenytoin is used when oral phenytoin loading is possible. The methods
      included a retrospective chart review of all patients receiving IV fosphenytoin
      in the emergency department. We prospectively derived criteria that identify
      patients with seizures who could receive oral phosphenytoin loading (awake on
      arrival, alert, no emesis, and lack of endotracheal intubation, repeated
      seizures, or status epilepticus after arrival). The setting of the study was at
      an urban, university hospital emergency department with an annual census of
      55,000 patients. The outcomes included the number of patients receiving IV
      fosphenytoin who could have received oral phenytoin loading. From February 1997
      to June 1999, 55 patients received IV fosphenytoin. Thirty of these patients
      (55%, 95% confidence interval 41%-68%) were felt to have received fosphenytoin
      appropriately. The remaining 25 (45%, 95% confidence interval 32%-59%) patients
      could have been loaded orally with phenytoin. In a single institution,
      fosphenytoin administration is inappropriate almost half the time. Oral phenytoin
      loading is less expensive and safe.

PMID- 11447517
TI  - Voice recognition software versus a traditional transcription service for
      physician charting in the ED.
AB  - This study was conducted to compare real-time voice recognition software to a
      traditional transcription service. Two emergency department (ED) physicians
      dictated 47 charts using a voice dictation software program and a traditional
      transcription service. Accuracy, word per minute dictation time and turnaround
      time were calculated from the data. The transcription service used in our study
      was more accurate than the voice recognition program with an accuracy of 99.7
      percent versus 98.5 percent for the voice recognition program. The average number
      of corrections per chart was 2.5 for the voice recognition program and 1.2 for
      the traditional transcription service. Turnaround time was much better using the
      computer voice recognition program with an average turnaround time of 3.65
      minutes versus a turnaround time of 39.6 minutes for the traditionally
      transcribed charts. The charts dictated using the voice recognition program were
      considerably less costly than the manually transcribed charts. In summary,
      computer voice recognition is nearly as accurate as traditional transcription, it
      has a much shorter turnaround time and is less expensive than traditional
      transcription. We recommend its use as a tool for physician charting in the ED.

PMID- 11447518
TI  - The UHP ultrasound protocol: a novel ultrasound approach to the empiric
      evaluation of the undifferentiated hypotensive patient.
AB  - This report describes a novel sonographic protocol for the evaluation of the
      undifferentiated hypotensive patient. This protocol combines components of 3
      sonographic applications: free fluid, cardiac, and abdominal aorta into a single
      protocol. We believe this protocol and its underlying principles should be a
      routine part of the empiric evaluation of the patient with undifferentiated
      hypotension or pulseless electrical activity.

PMID- 11447519
TI  - Electrocardiographic ST segment depression.
AB  - Traditionally, ST segment depression has been associated with acute coronary
      syndromes; this electrocardiographic pattern may also be found in patients with
      nonischemic events, such as left bundle branch block (LBBB), left ventricular
      hypertrophy (LVH), and those with therapeutic digitalis levels. Using the ECG as
      an adjunct in distinguishing those patients with acute coronary syndromes from
      those with more "benign," nonacute causes of STSD will obviously lead to
      divergent treatment and management plans. The following cases illustrate the use
      the ECG in patients presenting with chest pain and electrocardiographic ST
      segment depression attributable to an ACS, LVH, LBBB, or digitalis.

PMID- 11447520
TI  - Orthopedic pitfalls in the ED: scaphoid fracture.
AB  - Wrist injuries are frequently encountered in the emergency department. When a
      patient presents with such an injury, the possibility of scaphoid fracture must
      be at the top of the differential for the emergency practitioner. Unfortunately,
      these injuries can be missed on first presentation, as they are frequently
      radiographically occult. When left unrecognized and untreated, these injuries
      lead to a high incidence of long-term functional disability and chronic pain. The
      emergency physician needs to be vigilant for scaphoid fracture and be aggressive
      in both its diagnosis and treatment to avoid this practice pitfall. This review
      examines the clinical presentation, diagnostic techniques, and management options
      applicable to the emergency physician.

PMID- 11447521
TI  - Rhabdomyolysis associated with hyperthyroidism.

PMID- 11447522
TI  - Mixed-type hiatal hernia mimicking pulmonary cystic lesion diagnosed by oral
      urografin in ED.

PMID- 11447523
TI  - Friday the 13th and full-moon: the "worst case scenario" or only superstition?

PMID- 11447524
TI  - Attribution of causality in adverse drug reactions.

PMID- 11447525
TI  - Pharyngitis followed by hypoxia and sepsis: Lemierre syndrome.

PMID- 11447526
TI  - Urine discoloration secondary to metronidazole.

PMID- 11447527
TI  - Anterior dislocation of the humeral head from bungee jumping.

PMID- 11447528
TI  - Delayed, but acutely progressive epidural hematoma after mild head injury.

PMID- 11447529
TI  - Ultrasonography in patients with suspected acute cholecystitis.

PMID- 11447531
TI  - Aberrant artery as a source of bleeding in spontaneous hemopneumothorax.

PMID- 11447532
TI  - Out-of-hospital thrombolysis in cardiac arrest after unsuccessful resuscitation.

PMID- 11447533
TI  - Narcotic dependency in the sickle cell population.

PMID- 11447534
TI  - Hyponatremia after treatment of carcinoid tumor.

PMID- 11447535
TI  - Asystole after Rinne testing: Beware the easy fainter.

PMID- 11447536
TI  - CT scans for posttraumatic LOC.

PMID- 11447537
TI  - Naloxone: a potential false localizing sign.

PMID- 11447538
TI  - QT interval prolongation as predictor of early mortality in acute ischemic stroke
      patients.

PMID- 11447539
TI  - Ultrasound diagnosis of occult femoral hernia presenting with intestinal
      obstruction.

PMID- 11447540
TI  - Successful treatment of DIC with a serine proteinase inhibitor.

PMID- 11447541
TI  - Axillary nerve temperatures during radiofrequency capsulorrhaphy of the shoulder.
AB  - PURPOSE: The purpose of this study was to determine the temperatures along the
      course of the axillary nerve during radiofrequency (RF) capsulorrhaphy of the
      shoulder in a cadaver model. The hypothesis of this project was that temperatures
      capable of damaging neural tissue would be recorded during simulated RF
      capsulorrhaphy. TYPE OF STUDY: Basic science evaluation. METHODS: This study used
      9 fresh-frozen cadaver shoulder capsules removed en bloc along with the
      underlying axillary nerve and soft tissue. The axillary nerve was instrumented
      with 4 thermocouples placed along the course of the nerve (2 thermocouples
      anterior and 2 posterior to the 6 o'clock position, spaced 7 mm apart). Each of
      the specimens underwent RF thermal capsulorrhaphy during which the temperature at
      each of the thermocouple positions was continuously recorded. RESULTS: The
      average of the maximum temperature at each of the 4 positions measured along the
      course of the axillary nerve were 52.2 +/- 18.0 degrees C at the most anterior
      place probed, 45.8 +/- 5.44 degrees C (mid anterior), 44.5 +/- 8.7 degrees C (mid
      posterior), and 42.8 +/- 10.1 degrees C at the most posteriorly positioned probe.
      Two specimens had a maximum temperature greater than the 67 degrees C set point
      of the device, and 7 specimens had a maximum temperature greater than 45 degrees
      C in at least 1 thermocouple position. CONCLUSIONS: This study shows that heating
      of the axillary nerve can occur during RF capsular shrinkage of the shoulder and
      may potentially reach levels that can damage neural tissue.

PMID- 11447542
TI  - The use of arthroscopic thermal capsulorrhaphy to treat internal impingement in
      baseball players.
AB  - PURPOSE: To determine if reducing glenohumeral translation by arthroscopic
      thermal shrinkage would improve the results of arthroscopic treatment of internal
      impingement in baseball players. TYPE OF STUDY: Retrospective review.
      INTRODUCTION: Traditional treatment of internal impingement does not address the
      pathophysiology. Baseball players' shoulders routinely have glenohumeral laxity.
      Addressing this laxity by thermal capsulorrhaphy may improve the results in the
      treatment of these patients. Traditional treatment of labral and rotator cuff
      debridement and/or repair has had marginal results in regard to the most
      important criterion, return to competition. METHODS: Charts of all patients
      undergoing surgical arthroscopy of the shoulder for suspected internal
      impingement were analyzed. Patients were divided into 2 groups: traditional
      treatment (non-heat-probe group, NHP, n = 51) or traditional treatment plus
      thermal capsulorrhaphy (heat-probe group, HP, n = 31). Internal impingement was
      confirmed by physical examination and arthroscopic criteria. All participants
      were baseball players and follow-up was 30 months. Data were analyzed for initial
      return to play and continued participation 30 months after surgery. RESULTS: Mean
      time for return to competition was 7.2 months in the NHP group and 8.4 months in
      the HP group; 80% of the NHP group returned to competition compared with 93% of
      the HP group. At 30 months after surgery, 67% of the NHP group was back to
      competition compared with 90% of the HP group (P =.01). The HP group averaged 7
      degrees less external rotation than before surgery. There were no significant
      complications in either group. CONCLUSIONS: Thermal capsular shrinkage can be
      safely used in the treatment of internal impingement in the throwing athlete.

PMID- 11447543
TI  - Arthroscopic shoulder surgery with epinephrine saline irrigation.
AB  - PURPOSE: To determine whether dilute epinephrine saline irrigation (0.33 mg/L)
      delivered by a pressure-controlled pump would significantly reduce intraoperative
      bleeding during routine arthroscopic shoulder surgery and, in addition, to
      investigate potential adverse cardiovascular reactions of adding epinephrine to
      the irrigation fluid. TYPE OF STUDY: Prospective, randomized, double-blinded,
      placebo-controlled study. METHODS: Fifty-four patients requiring arthroscopic
      shoulder surgery were randomly assigned to either an epinephrine group that
      received dilute epinephrine irrigation by a pressure-controlled pump or to a
      placebo group that received plain saline irrigation by a pressure-controlled
      pump. Intraoperative, intra-articular bleeding was estimated by multiplying the
      total volume of the irrigation fluid used with the hemoglobin concentration in
      the irrigation fluid. Postoperatively, the surgeon rated the clarity of the
      visual field during the arthroscopy by a visual analogy scale. RESULTS:
      Intraoperative bleeding was significantly reduced (P =.008) and the clarity of
      the visual field was significantly better (P =.0007) in the group of patients
      receiving dilute epinephrine irrigation compared with the group of patients
      without epinephrine added to the irrigation fluid. CONCLUSIONS: The addition of
      epinephrine to irrigation fluid seems to reduce intra-articular bleeding during
      routine arthroscopic shoulder surgery and may improve visualization. Furthermore,
      no cardiovascular adverse reactions were observed resulting from the intra
      articular epinephrine administration.

PMID- 11447544
TI  - Arthroscopic release for lateral epicondylitis.
AB  - PURPOSE: This study was performed to review the results of our early experience
      with recalcitrant lateral epicondylitis treated arthroscopically. TYPE OF STUDY:
      This study is a case series consisting of consecutive patients with lateral
      epicondylitis treated arthroscopically by 1 surgeon. METHODS: Patients failing a
      minimum of 6 months of conservative treatment underwent arthroscopic release of
      the extensor carpi radialis brevis (ECRB) origin using the proximal medial and
      proximal lateral portals. Associated intra-articular pathology was noted and
      addressed. The ECRB lesions were classified according to their gross morphology
      and resected with a shaver. The lateral epicondyle was then decorticated with a
      burr. RESULTS: Sixteen patients with recalcitrant lateral epicondylitis were
      treated with arthroscopic release of the ECRB origin on the lateral epicondyle.
      Of the 16 elbows undergoing surgery, 5 (31.3%) were noted to have a type I
      lesion, characterized as fraying of the undersurface of the ECRB. Five (31.3%)
      had a type II lesion noted by linear tears within the ECRB, and 6 (37.5%) had a
      type III lesion, consisting of a partial or complete avulsion of the ECRB origin.
      Concurrent intra-articular pathology (synovitis, osteophytes) was noted in 3 of
      16 elbows (18.8%) and was addressed arthroscopically. All patients were followed
      up for a minimum of 1 year; however, 4 patients were lost to follow-up for this
      retrospective review due to military reassignment. Follow-up was obtained on 12
      of 16 (75%) of patients at an average length of 24.1 months (range, 15 to 33
      months). All patients reported improvement with the procedure. The average return
      to unrestricted work was 6.0 days (range, 0 to 28 days). CONCLUSIONS:
      Arthroscopic release effectively treats lateral epicondylitis while also
      affording visualization of the joint space to address associated intra-articular
      pathology. Additionally, arthroscopic release is minimally invasive and allows
      early rehabilitation and return to normal activities.

PMID- 11447545
TI  - Anterior cruciate ligament reconstruction in men and women: An outcome analysis
      comparing gender.
AB  - PURPOSE: Recent studies have shown that female athletes suffer a higher incidence
      of anterior cruciate ligament (ACL) tears than comparable male athletes. The
      purpose of this study was to evaluate the effect gender has on outcome in ACL
      reconstruction using bone-patellar tendon-bone autograft. TYPE OF STUDY:
      Retrospective case review and outcome study. METHODS: A retrospective review of a
      single surgeon's practice revealed 279 ACL reconstructions that met our criteria
      for inclusion. Two-hundred forty-nine of these patients (91%) were contacted. Two
      hundred (72%) were evaluated with physical examination, KT-1000 testing,
      functional testing, and radiographic evaluation. Outcome was assessed with
      Tegner, Lysholm, modified HSS, and Cincinnati Knee rating scales, as well as the
      SF-36 health survey and a self-administered questionnaire. There were 137 men and
      63 women. Data were evaluated with Wilcoxon rank sum testing, analysis of
      variance testing, chi-square analysis, and the Student t test. The level of
      significance was set at P <.05. RESULTS: Postoperatively, no differences were
      noted on Lachman, anterior drawer, pivot shift, or functional testing in either
      groups. Male patients had a significantly greater mean prone heel height
      difference (1.80 v 1.10 cm, P =.0018) and mean KT-1000 maximum manual side-to
      side difference (0.76 v 1.73 mm, P =.014). However, no differences were noted in
      the percentage of patients with greater than 5-mm side-to-side difference, with 5
      men (4%) and 2 women (3%) classified as arthrometric failures. No differences
      were noted in mean Tegner, Lysholm, Noyes Cincinnati, and modified HSS scores.
      Men had significantly lower HSS radiographic scores (24.98 v 26.22, P =.0016).
      Men and women were compared with gender-matched controls for SF-36 testing, and
      women scored higher compared with controls than did men in the Role Physical,
      Body Pain, and General Health categories. No differences were noted in either
      group regarding donor-site pain, patellofemoral crepitance, or problems with
      stair climbing. Ninety-six percent of men and 98% of women would have had the
      surgery over again given similar circumstances. CONCLUSIONS: Objective criteria
      failed to detect clinically significant differences in physical examination and
      arthrometric results between men and women. Knee rating scale scores were
      similar. Comparable outcome with high satisfaction and equal success can be
      expected in both men and women undergoing ACL reconstruction using bone-patellar
      tendon-bone autograft. No basis exists for the inclusion of gender as a
      determining factor regarding the decision to perform ACL reconstructive surgery
      with bone-patellar tendon-bone autograft.

PMID- 11447546
TI  - Bone tunnel remodeling at the site of biodegradable interference screws used for
      anterior cruciate ligament reconstruction: 5-year follow-up.
AB  - PURPOSE: The purpose of this prospective study was to review, using expanded
      clinical-assessment tools, the long-term results of the local effects of a
      bioabsorbable interference screw (copolymer 85/15 D,L lactide/glycolide) in
      anterior cruciate ligament (ACL) reconstruction. TYPE OF STUDY: This prospective
      study was initiated in May 1993. The inclusion criteria for patient selection
      included rupture of the ACL in athletic patients without involvement of the
      collateral ligaments, arthroscopic ACL reconstruction using middle third of the
      ligamentum patella, and magnetic resonance imaging (MRI) and plain radiographic
      examinations of the knee joint during follow-up. MATERIALS: Between May 1993 and
      October 1994, 32 patients were enlisted in the study; 48 patients did not fit the
      inclusion criteria. There were 25 men 7 women. The average age was 29.1 years
      (range, 19 to 50 years). There were 21 right knees and 11 left knees. The follow
      up examinations were performed by an independent examiner. There were 28 patients
      available for follow-up at a medium of 5.2 years (range, 4.1 to 6.4 years). The
      evaluation included various testing systems (i.e., OAK, IKDC, Lysholm) as well as
      MRI and plain radiographic studies to investigate the longevity of the implant
      and potential adverse effects of this new bioabsorbable material. RESULTS: The
      clinical results were good. The OAK score (Orthopadische Arbeitsgruppe Knie)
      showed 93% excellent and good results, and 7% fair results. The IKDC and Lysholm
      scores were 92% and 96% good and excellent results, respectively. MRI showed bone
      remodeling and new bone formations at the site of the implant in the femoral as
      well as in the tibial bone tunnel at follow-up. No cystic or osteolytic changes
      where seen on MRI or plain radiographs. CONCLUSIONS: This study showed the
      correlation between histology and MRI: there was minimal surgical-site edema,
      minimal reaction to this material, and complete replacement by new bone formation
      of the previous site of this implant. At 5 years, this bioabsorbable interference
      screw appeared clinically safe and effective for fixation of bone blocks during
      ACL reconstruction and MRI showed complete absorption and replacement with new
      bone.

PMID- 11447547
TI  - The effect on leg strength of tourniquet use during anterior cruciate ligament
      reconstruction: A prospective randomized study.
AB  - PURPOSE: The purpose of this study was to prospectively evaluate the effect of
      tourniquet use during endoscopic anterior cruciate ligament (ACL) reconstruction
      surgery on dorsiflexion strength, plantarflexion strength, quadriceps strength,
      and calf and thigh girth. TYPE OF STUDY: The study was a prospective, double
      blind, randomized clinical trial. METHODS: Forty-eight patients were
      prospectively randomized into 2 groups: (1) tourniquet use during surgery (T)
      and, (2) no tourniquet use during surgery (NT). Within 1 week before ACL
      reconstruction, all patients were evaluated for isometric plantarflexion and
      dorsiflexion strength, thigh strength, and thigh and calf girth. These same
      measurements were repeated 3 weeks postoperatively. At 6 months, isokinetic
      quadriceps strength was evaluated at 60 degrees per second. All patients
      underwent ACL reconstruction using a patella-tendon autograft and a tourniquet
      was placed on the affected extremity. In all 25 T patients, the tourniquet was
      inflated to 300 mm Hg. The average tourniquet time was 85 +/- 7 minutes (range,
      51 to 114 minutes). RESULTS: ACL reconstruction resulted in a significant
      decrease in thigh girth (P <.01), calf girth (P <.01), dorsiflexion strength (P
      <.01), and plantarflexion strength (P <.05) at 3 weeks postoperatively in both
      groups. The T group had a greater decrease in thigh girth than the NT group (P
      <.05). Tourniquet use did not have an effect on calf girth (P =.53), dorsiflexion
      strength (P =.17), or plantarflexion strength (P =.32) at 3 weeks
      postoperatively. Tourniquet use also had no effect on quadriceps strength at 6
      months postoperatively (P =.78). CONCLUSIONS: Tourniquet use of less than 114
      minutes during ACL reconstruction had no effect on the strength of the lower
      extremity after surgery.

PMID- 11447548
TI  - Osteochondritis dissecans of the lateral femoral condyle following total
      resection of the discoid lateral meniscus.
AB  - PURPOSE: The purpose of this study was to describe the clinical presentation of 6
      athletically active children with symptomatic osteochondritis dissecans (OCD) of
      the lateral femoral condyle following total resection for a torn discoid lateral
      meniscus and to discuss its cause. TYPE OF STUDY: Case series. METHODS: Six
      patients in whom OCD affecting the lateral femoral condyle developed after total
      resection of the discoid lateral meniscus participated in a detailed clinical,
      radiologic, and arthroscopic review. The average age at the time of meniscectomy
      was 9 years (range, 6 to 12 years). At a mean of 50 months (range, 36 to 65
      months) after surgery they developed recurrent pain in the treated knee; all had
      radiologic abnormalities at the lateral femoral condyle consistent with OCD.
      Before the recurrence of pain, all patients had been continuously engaged in
      sports activity. Radiologic and arthroscopic findings of the OCD lesions were
      assessed. Clinical outcomes of surgical treatment for OCD were also documented.
      RESULTS: The radiographic evaluation showed all lesions to be in the central
      portion of the lateral femoral condyle on the anteroposterior views and
      posteriorly next to a line extending distally from the posterior femoral cortex
      on the lateral views. Arthroscopic evaluation revealed softening in 2 knees, a
      separated fragment in 2 knees, and a completely loose fragment in 2 knees. All
      lesions were treated surgically, including 2 drillings of the lesion, 2 fixations
      of separated fragment, and 2 excisions of loose bodies with drilling. At an
      average follow-up period of 51 months (range, 22 to 77 months), all patients but
      1 were asymptomatic. CONCLUSIONS: Repeated impaction in sports activities on the
      immature osteochondral structures under altered mechanical force transmission
      after total resection of the discoid meniscus might be a predisposing factor in
      the development of OCD in the lateral femoral condyle.

PMID- 11447549
TI  - The effects of monopolar radiofrequency energy on intact and lacerated ovine
      menisci.
AB  - PURPOSE: To evaluate the effect of monopolar radiofrequency energy (RFE) on
      intact and lacerated meniscal tissue. TYPE OF STUDY: In vitro study. Application
      of monopolar RFE to soft tissue for treatment of various musculoskeletal
      disorders has been explored recently, although its effect on meniscal tissue has
      not been critically evaluated. Monopolar RFE denatures and fuses collagen. Given
      that menisci are composed primarily of type I collagen, we proposed that RFE
      could be applied to meniscal tears with minimal effect on healthy meniscal
      tissue. METHODS: Adult sheep menisci were given 1 of 2 treatments (65 degrees C,
      15 W or 75 degrees C, 10 W) with a monopolar RFE generator. Specimens were
      processed for scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), light microscopy, and confocal laser microscopy. A computer
      based area-determination program was used to calculate the treated area in
      confocal laser images. RESULTS: SEM changes in treated tissue consisted of
      surface smoothing with collagen fibril fusion. Changes apparent with TEM included
      tissue homogenization with loss of cross-striations and fusion of collagen
      fibrils. Histologic changes consisted of fusion and loss of collagen fiber
      individualization, pyknosis of fibrochondrocyte nuclei, and loss of lacunae
      surrounding fibrochondrocytes. There were clear demarcations between treated and
      untreated tissue with both treatments. There were no discernible differences
      between treatment groups on SEM, TEM, or histologic examination. Confocal laser
      microscopic evaluations showed distinct treatment areas. The mean area affected
      ranged from 6.6% for 65 degrees C, 15 W to 8.8% for 75 degrees C, 10 W.
      CONCLUSIONS: The primary effects of monopolar RFE treatment of menisci in this
      study were consistent with thermal tissue damage limited to the treatment area.
      Monopolar RFE treatment of a meniscal laceration may stabilize the tear by fusing
      collagenous tissue in the surrounding area and prevent propagation along tissue
      lines. This study presents preliminary in vitro results. Further studies are
      necessary before clinical applications can be recommended.

PMID- 11447550
TI  - Negative knee arthroscopy: Is it really negative?
AB  - PURPOSE: To evaluate the outcome of patients in whom knee arthroscopy proved to
      be normal. TYPE OF STUDY: Retrospective study. METHODS: Knee arthroscopy is
      probably the most common procedure performed in orthopaedic practice. A number of
      patients who undergo this procedure do not have any abnormality detected. Is
      negative arthroscopy really such an unnecessary procedure? Hospital records of
      patients who had undergone knee arthroscopy were retrospectively studied and all
      patients with a normal knee arthroscopy were selected. Fifty-three patients (55
      knees) with a normal arthroscopy were included into the study. Patients were then
      interviewed either by telephone or questionnaire to ascertain current symptoms,
      job changes, and patient perception of the procedure. RESULTS: The mean follow-up
      was 43 months. Fifty percent of the patients had a history of injury, and the
      preoperative diagnosis was thought to be a meniscal lesion or a rupture of the
      anterior cruciate ligament in 38% of patients. Sixty-eight percent of the
      patients felt that they were better and there were no complications. The
      incidence of all symptoms were significantly reduced after arthroscopy.
      CONCLUSIONS: A significant number of patients felt that they were better after
      the knee arthroscopy. The reason for this is not entirely clear. It may well be
      attributable to a placebo effect, the fact that patients now know that there is
      no abnormality and learn to live with the symptoms, or there may be an additional
      benefit of the procedure itself.

PMID- 11447551
TI  - Thermal capsular shrinkage: Basic science and clinical applications.
AB  - Recently, the use of thermal energy to shrink the redundant glenohumeral joint
      capsule in patients with instability has generated a great deal of interest.
      Proponents assert that the procedure avoids the need for an open stabilization
      and it may be used as an adjunct to an open or arthroscopic capsulolabral repair.
      The use of nonablative thermal energy to shrink soft-tissue collagen appears to
      induce ultra-structural and mechanical changes at or above 60 degrees C. The
      microscopic changes reflect the unwinding of the collagen triple helix and loss
      of the fiber orientation. The fibrils contract into a shortened state and
      reactive fibroblasts have been shown to grow into this treated area and
      synthesize the collagen matrix. The biomechanical properties of the tissue do not
      appear to be detrimentally altered if shrinkage is limited to less than 15% and
      if ablation or excess focal treatment is avoided. The endpoint of optimal
      shrinkage is not known and clinical estimations of tissue changes and volumetric
      reduction are used as guides to treatment. The first clinical follow-up study was
      only recently published in the peer-reviewed literature and prior preliminary
      reports were optimistic regarding the use of thermal energy for the treatment of
      glenohumeral instability. Thermal capsular shrinkage has been used as an adjunct
      to a capsulolabral repair, as well as an isolated treatment for the disorders of
      internal impingement and multidirectional instability. Additional evaluation is
      necessary to determine the optimal quantity of energy needed for tissue shrinkage
      without inadvertent tissue destruction. The long-term clinical effect, mechanical
      properties, and durability of the newly produced collagen need to be analyzed
      further. The basic science and clinical applications of this newly applied
      technology are reviewed in this article.

PMID- 11447552
TI  - How would you treat the partially torn biceps tendon?

PMID- 11447553
TI  - Synovial knee fistula: A cause of prolonged morbidity.
AB  - Postarthroscopy knee fistulae may lead to prolonged morbidity. A 62-year-old man
      presented with a synovial knee fistula 4 weeks after knee arthroscopy, which was
      confirmed by magnetic resonance imaging. He was treated with antibiotics and knee
      immobilization that resulted in closure of the fistula. He then developed
      recurrent septic knee effusion that required arthroscopic washout, further
      antibiotic treatment, and physiotherapy. The patient's clinical condition
      resolved after a further 6 weeks. This case shows that not all fistulae resolve
      spontaneously; they may lead to prolonged morbidity and necessitate further
      treatment. We also wish to note that magnetic resonance imaging is a useful
      diagnostic tool in place of the traditional sinogram.

PMID- 11447554
TI  - Injuries to the posterolateral aspect of the knee accompanied by compression
      fracture of the anterior part of the medial tibial plateau.
AB  - We present 12 cases of patients with injury to the posterolateral aspect of the
      knee accompanied by a compression fracture of the anterior part of the medial
      tibial plateau. There were 11 male patients and 1 female patient with an average
      age of 26 years (range, 17 to 44 years). There were 4 cases of posterolateral
      rotatory instability and 8 cases of straight lateral instability of the knee. The
      size of the compression fracture was classified into 2 types, small (8 cases) and
      large (4 cases). Although the mechanism of injury was considered to be
      hyperextension and varus force, the pattern of cruciate ligament injuries varied
      from case to case. The following 3 questions should be considered to determine
      which cruciate ligament is damaged: (1) Was the ipsilateral foot fixed to the
      ground? (2) Was forward inertia involved? (3) Was there a direct blow to the
      anteromedial aspect of the tibia or to the femur? Accompanied fractures of the
      medial tibial plateau were considered to have been compressed by the medial
      femoral condyle. The size of the accompanying compression fracture varied; 7 of 8
      cases with a small-type fracture had posterior cruciate ligament injuries and 3
      of 4 cases with a large-type fracture had anterior cruciate ligament injuries.
      The size of the fracture is determined by which point of the medial tibial
      plateau touched the medial femoral condyle. We propose that a compression
      fracture of the anterior part of the medial tibial plateau indicates a coexistent
      posterolateral aspect injury, and that especially a small compression fracture
      strongly suggests an accompanying posterior cruciate ligament injury, as well.

PMID- 11447555
TI  - Patellar tendon rupture 3 years after anterior cruciate ligament reconstruction
      with a central one third bone-patellar tendon-bone graft.
AB  - Use of the central one third bone-patellar tendon-bone autograft is an accepted
      technique for anterior cruciate ligament (ACL) reconstruction. Patellar tendon
      rupture following ACL reconstruction is an acknowledged, although rarely
      reported, complication of this procedure. Of the limited patellar tendon rupture
      cases reported in the literature, most are described early in the postoperative
      period. We present a case of late patellar tendon rupture more than 3 years after
      uneventful ACL reconstruction in a 32-year-old man.

PMID- 11447556
TI  - Arthroscopic osteochondral autograft transplantation for chondral lesion of the
      tibial plateau of the knee.
AB  - Arthroscopic osteochondral autograft transplantation is often used to treat
      chondral/osteochondral lesions of the femoral condyle of the knee. However,
      arthroscopic autologous osteochondral grafting to the tibial plateau has not been
      reported. We report the surgical technique and the clinical course of a patient
      who underwent engraftment by this method. A 26-year-old man developed symptoms of
      pain and catching in his knee. Arthroscopy revealed a deep chondral lesion, 10 x
      15 mm in size, down to the subchondral bone on the posterocentral area of the
      lateral tibial plateau. The injured cartilage was debrided using a curette and an
      abrader until normal healthy cartilage bordered the debrided defect. An
      osteochondral plug, 10 mm in diameter and 20 mm long, the chondral surface of
      which was orientated 25 degrees obliquely, was harvested from the most peripheral
      and proximal part of the lateral patellar groove. A bony hole was created in the
      center of the defect through the tibia using a core reamer. The osteochondral
      plug was inserted from the tibial window through the bony hole. To enhance the
      stability of the osteochondral fragment, bioactive ceramic fillers were used to
      fill the space below the plug. A second-look arthroscopy 10 months after surgery
      showed that the grafted osteochondral plug was well adapted and integrated into
      the surrounding cartilage on the lateral tibial plateau.

PMID- 11447557
TI  - Semitendinosus tenodesis for medial instability of the knee.
AB  - A new technique of semitendinosus tenodesis has been developed to treat medial
      instability of the knee. The semitendinosus tendon was sectioned at the
      musculotendinous junction. The accessory insertion of the tendon was dissected to
      be overlapping and parallel to the anterior band of the medial collateral
      ligament. An isometric point on the femur was located around the medial
      epicondyle. A bony trough was created just above the isometric point and a screw
      with washer was placed. The semitendinosus tendon was looped around the screw and
      the screw was tightened to hold the tendon in place. The free end of the tendon
      was pulled obliquely backward and passed through the insertion of the direct head
      of the semimembranosus tendon to reconstruct the posterior oblique ligament. The
      semitendinosus tendon reinforced both the medial collateral ligament and the
      posterior oblique ligament.

PMID- 11447558
TI  - Reconstruction by biceps tendon rerouting for posterolateral rotatory instability
      of the knee: Modification of the Clancy technique.
AB  - We present a biceps rerouting technique for posterolateral rotatory instability
      using a modification of the biceps femoris tendon tenodesis of Clancy. The
      distinguishing features of this technique are the approach to the lateral femoral
      epicondyle through the interval between the iliotibial band and biceps femoris
      muscle, and fixation of the transferred biceps tendon at the isometric point.
      Reconstruction for posterolateral rotatory instability by modified biceps tendon
      rerouting can result in objectively and functionally acceptable knee function.

PMID- 11447559
TI  - Split biceps femoris tendon reconstruction for proximal tibiofibular joint
      instability.
AB  - Recurrent instability of the proximal tibiofibular joint is an infrequently
      diagnosed abnormality. We present a new technique for reconstructing the joint
      using a split biceps femoris tendon passed through a bone tunnel in both the
      proximal tibial metaphysis and fibular head. The case report is also presented.
      The procedure offers an anatomic reconstruction and firm stabilization. It allows
      normal motion of the proximal tibiofibular joint and preserves the normal
      mechanics of the ankle. This procedure is an excellent alternative to resection
      of the fibular head, transarticular arthrodesis, or pseudoarthrosis focus at the
      fibular head.

PMID- 11447560
TI  - Obtaining intra-articular bone grafts arthroscopically for intra-articular
      grafting.
AB  - Autogenous bone graft is frequently necessary for arthroscopic procedures and
      even small open procedures that involve cruciate revision, osteochondritis
      dissecans repair, and fracture reduction and internal fixation. Currently used
      sites to obtain bone graft are the iliac crest and Gerdy's tubercle. This article
      describes an arthroscopic technique for harvest of small amounts of bone graft
      from the distal femur. This avoids the morbidity of the extra-articular harvest.
      Tube harvesters frequently used for osteochondral autografts are the primary tool
      required for this technique. However, as described, the obtaining of bone graft
      is much less technically exacting than when procuring osteochondral bone plugs.
      This provides a safe, simple way to obtain extra autogenous bone at minimal
      additional operative morbidity.

PMID- 11447561
TI  - Muscular buttonholing: An unusual cause of irreducible knee dislocation.
AB  - In cases of irreducible knee dislocation, all the medial joint structures have
      been reported to be the obstructing tissue. The case presented, the first in the
      English-language literature, is buttonholing of the femoral condyle through the
      vastus medialis muscle. Entrapment of the muscle bundle was diagnosed
      preoperatively using magnetic resonance imaging scans. The joint could be reduced
      easily, following sectioning of the muscle bundle.

PMID- 11447562
TI  - Localized pigmented villonodular synovitis of the knee.
AB  - Localized pigmented villonodular synovitis (PVNS) of the knee is a rare,
      idiopathic condition presenting with symptoms that can be confused with various
      other intra-articular pathologies. The condition is usually monoarticular, the
      knee being most commonly affected. If totally excised, complete cure can be
      achieved and recurrence is very rarely reported. In this report, we present 4
      cases of patients with different symptomatology but all with PVNS of the knee who
      underwent arthroscopic treatment. At short-term follow-up, all patients had
      complete recovery of their symptoms with no apparent recurrence.

PMID- 11447563
TI  - Progressive articular cartilage loss following radiofrequency treatment of a
      partial-thickness lesion.
AB  - Arthroscopic debridement of partial-thickness articular cartilage lesions is a
      common orthopaedic procedure. Radiofrequency treatment has rapidly gained
      clinical acceptance despite the lack of prospective studies involving second-look
      arthroscopy to determine long-term sequelae. We report a case in which a partial
      thickness lesion that had been treated with radiofrequency ablation showed
      progressive thinning of the articular surface.

PMID- 11447564
TI  - Acute bucket-handle tear of the medial meniscus in a golfer.
AB  - This is the first case report of an acute bucket-handle tear in an amateur
      golfer. The injury occurred during the follow-through phase of the golf swing.
      The rate of incidence of knee injuries in golfers is only 10%. There is a
      difference in the injury pattern between amateur and professional golfers;
      amateurs are more likely to sustain injuries related to poor swing technique.
      Professional golfers, on the other hand, report more injuries related to overuse.
      Although forces in the knee are relatively minor in this sport, acute injuries
      can happen when poor technique is used.

PMID- 11447565
TI  - Bilateral absence of the anterior cruciate ligament.
AB  - We report a rare case of bilateral absence of the anterior cruciate ligament in
      an adolescent. The clinical picture, the diagnostic and therapeutic approach, the
      arthroscopic appearance and the follow-up are described. The available literature
      is discussed.

PMID- 11447566
TI  - Pathological gambling: a current perspective.

PMID- 11447567
TI  - The epidemiology of pathological gambling.
AB  - Increased attention has been given to the disorder of pathological gambling,
      especially since the formation of the latest Presidential Commission to study its
      social and economic impact on the nation. Researchers have experienced difficulty
      in establishing the prevalence of pathological gambling disorder attributable to
      several factors, namely: debate and confusion on the best way to define and
      classify the disorder; assessments of the disorder that are not diagnostic or
      comprehensive; and, methodological weaknesses in the majority of gambling studies
      caused primarily by sampling biases. This article summarizes prevalence estimates
      of pathological gambling disorder in the general population and for
      subpopulations while addressing the difficulties inherent in their
      interpretation. Recommendations are offered for future research into this
      disorder.

PMID- 11447568
TI  - Pathological gambling: addiction or compulsion?
AB  - There is considerable debate about the appropriate conceptualization of
      pathological gambling and its place in psychiatric nosology. The authors examined
      the existing research on different areas of pathological gambling to find
      evidence for a particular model of this disorder. There are 2 dominant models of
      pathological gambling: as a nonpharmacologic addiction and as an obsessive
      compulsive spectrum disorder. The data available from different areas seem to
      converge in suggesting that pathological gambling has characteristics that are
      similar to those of substance abuse, and less close to those of obsessive
      compulsive disorder, although those conceptualizations are not mutually
      exclusive. An alternative model of pathological gambling is that it constitutes a
      heterogeneous disorder with some subtypes resembling obsessive-compulsive
      disorder, and other subtypes being closer to substance abuse disorders. Improved
      understanding of the conceptualization of this disorder may help improve the
      quality of the treatments available.

PMID- 11447569
TI  - A behavioral approach to understanding and treating pathological gambling.
AB  - This report provides a behavioral account of gambling and its treatment. It
      describes the similarities between gambling and other behaviors maintained by
      intermittent schedules of reinforcement, the relationship between response cost
      and gambling behaviors, and how magnitudes of reinforcers affect gambling
      behaviors. In addition, the relationship between immediacy of reinforcement and
      behavior is described. Using these behavioral phenomena, behavioral and cognitive
      behavioral treatments of pathological gambling are described. Finally, we present
      the rationale and framework for our cognitive-behavioral treatment, and we
      provide a behavioral interpretation of 12-step groups.

PMID- 11447570
TI  - The psychopharmacology of pathological gambling.
AB  - We discuss the rationale of the pharmacological approaches to pathological
      gambling and review the current status of drug treatments in this area.
      Specifically, we summarize the treatment study results of serotonin reuptake
      inhibitors, mood stabilizers, and opioid antagonists in pathological gambling. We
      also briefly describe the animal and human studies of other pharmacologic agents
      that show future promise in treating this disorder. Finally, we discuss a
      research agenda to be addressed in future drug treatment studies in pathological
      gambling.

PMID- 11447571
TI  - The genetics of pathological gambling.
AB  - Problem and pathological gambling (PG) occurs in about 5% of Americans. Gambling
      is associated with substantial psychosocial and psychiatric health problems, and
      the increasing ease of access to gambling may increase its future prevalence.
      Therefore, it is important to gain greater insight into the causes of PG. Family
      studies of PG are consistent with a substantial familial impact on vulnerability
      to PG. However, family studies cannot distinguish genetic from family
      environmental influences. By contrast, the study of twin pairs permits the
      genetic and environmental influences on PG to be estimated. The study of gambling
      behavior among 3,359 twin pair members of the Vietnam Era Twin Registry suggests
      that: (1) inherited factors explain a substantial proportion of the variance in
      the report of symptoms of gambling; (2) there is a single continuum of genetic
      vulnerability that underlies gambling problems of varying severities; and, (3)
      the co-occurrence of PG with conduct disorder, antisocial personality disorder,
      and alcohol abuse/dependence is partially explained by genes that influence both
      PG and these other psychiatric disorders. Neurophysiological correlates of
      gambling problems and genetically based differences in neurotransmitter systems
      may provide biological mechanisms that explain the genetic basis for a
      predisposition to PG.

PMID- 11447572
TI  - Neurobiology of decision-making: risk and reward.
AB  - Neurological patients with bilateral ventromedial (VM) lesions of the prefrontal
      cortex often deny, or they are not aware that they have a problem. Furthermore,
      they often pursue actions that bring some reward in the immediate run, despite
      severe long-term consequences such as the loss of job, home, and family. The
      somatic marker hypothesis, which provides an account of this defect in decision
      making, posits that the impairment is the result of defective activation of
      somatic markers that normally function as covert or overt signposts for helping
      with the process of making choices that are advantageous to the organism. Failure
      to enact somatic states results from dysfunction in a neural system in which the
      VM cortex is one critical region. However, other neural regions, including the
      amygdala, and somatosensory cortices (SI, SII, and insula) are also hypothesized
      to be components of that same neural system. Recent evidence reveals that
      substance abusers suffer from decision-making deficit akin to that seen with
      patients with VM lesions. Thus, the strategies used to study decision-making in
      neurological patients have direct implications for understanding several
      neuropsychiatric disorders including addiction and pathological gambling.

PMID- 11447573
TI  - The neurobiology of pathological gambling.
AB  - Despite relatively high prevalence rates and significant morbidity and mortality
      associated with pathological gambling (PG), our understanding of the
      neurobiological basis of PG lags in comparison to that for other psychiatric
      illnesses of comparable magnitude. An improved understanding of the neurobiology
      of PG would facilitate targeted investigations into more effective treatments.
      Emerging data suggest shared neurobiological features determine in part
      pathological gambling and substance use disorders. These findings both challenge
      current conceptualizations of addictions and provide a substantial basis of
      knowledge on which to design investigations into the understanding and treatment
      of pathological gambling. The findings that substance use disorders and the
      behavioral "addiction" of PG share common causative features raise the question
      as to what extent other compulsive disorders (eg, compulsive shopping, compulsive
      sexual behaviors, compulsive computer use) might be biologically related.

PMID- 11447575
TI  - Organizational response of normal tissues to irradiation.
AB  - A central tenet in the treatment of cancer patients with radiation has been that
      normal tissue complications were related to the volume of the tissue irradiated,
      although the mechanisms underlying this phenomenon were poorly understood. The
      advent of new treatment techniques, such as three-dimensional (3-D) conformal
      treatments, drove the developers of models to evaluate the resultant complex dose
      distribution plans, particularly in terms of predicting normal tissue
      complications. However, a lack of experimental data on the effects of changing
      volume on normal tissue responses made it difficult to substantiate these models.
      Consequently, radiobiology research on normal tissue dose volume effects in
      experimental animal models was initiated, providing considerable insight into the
      effect of changing volume on normal tissue response for a large number of
      tissues. This paper summarizes these data and the potential impact of new
      concepts and data in molecular radiation biology on dose volume effects in normal
      tissues.

PMID- 11447576
TI  - Modeling the effects of inhomogeneous dose distributions in normal tissues.
AB  - Conformal radiation therapy frequently produces inhomogeneous dose distributions
      in normal tissues near the target. Most mathematical models of normal tissue
      complication probabilities (NTCP) are based on uniform whole or partial organ
      irradiation, and the model parameters are chosen to obtain agreement with
      clinical outcomes in these simple situations. Frequently used NTCP models and
      methods for including inhomogeneous dose distributions in model calculations are
      outlined in this report. It has been found that the model adopted may
      qualitatively affect prediction of complications. Limitations placed on current
      models by the scarcity of reliable complications data and other approaches to
      using the calculated dose distribution to predict NTCP are discussed.

PMID- 11447577
TI  - The controversies and pitfalls in modeling normal tissue radiation injury/damage.
AB  - Highly conformal fields have become achievable in routine clinical practice. The
      optimal shape of the resultant dose distributions depends on information that is
      not currently available. This missing information is the dose-volume response of
      the normal tissues at risk. These functions are now the subject of aggressive
      research. The research involves collecting the dose-response data, modeling the
      dose-response function, and fitting the models to the data. The controversies
      addressed here influence the selection of the biomathematical model that one
      might use to describe such a function. The form that the dose-volume response
      function takes depends on the nature of the volume effect. The nature of the
      volume effect for a given radiation response is the subject of considerable
      debate. Related to this debate, this report addresses the existence of the volume
      effect, the existence of a threshold volume, and the existence of functional
      subunits. The pitfalls relate to the problems in accurate determination and
      application of the dose-response functions.

PMID- 11447578
TI  - Partial irradiation of the rectum.
AB  - Data gathered from dose escalation protocols for the treatment of prostate
      cancers conducted in the past 10 years have shown that rectal toxicity can be
      controlled by the use of careful conformal techniques. The most severe
      complications of rectal irradiation (obstruction and fistula requiring colostomy)
      have been essentially eliminated. The most frequent gastrointestinal
      complications of conformal radiotherapy of prostate cancer are now rectal
      bleeding associated with telangiectatic changes to the vasculature of the
      submucosa, and in severe cases, ulceration requiring cautery procedures and or
      transfusion. The benefits of 3-dimensional conformal radiotherapy (3D-CRT) are
      strongly technique dependent, with a strong dose response for single techniques
      for prescription doses over 70 Gy. Studies of rectal motion show that the
      anterior wall can move approximately 1 cm during treatment, so portions of the
      anterior rectal wall will regularly receive the full prescription dose if
      posterior margin sizes >/= 1 cm are used in designing the planning target volume
      (PTV). There is strong evidence that increased rectal shielding and posterior PTV
      margin sizes approximately 0.6 cm reduce rectal complication rates. Despite
      uncertainties due to rectal motion, studies of dose-volume histograms (DVHs) show
      that rectal toxicity is strongly influenced by the percent volumes of rectal wall
      exposed to doses approximately 70 Gy and higher. Recent data suggests that
      percent volumes of rectal wall exposed doses between 40 to 50 Gy, and the
      existence of a reserve of unexposed tissue may also play a role in determining
      rectal bleeding rates.

PMID- 11447579
TI  - Partial irradiation of the heart.
AB  - Radiation-induced heart disease (RIHD) includes pericarditis, ischemic heart
      disease, and myocardial infarction and leads in some cases to fatal
      complications. It has been shown that the increased survival due to radiotherapy
      could be negated by excess deaths from RIHD in breast cancer radiotherapy for
      left-sided tumors. Subclinical effects following irradiation have been detected
      in several studies both of breast cancer and Hodgkin's irradiation. The dose
      volume response relationships describing cardiac complications have been studied
      for pericarditis and cardiac mortality by means of biologic models, including the
      well-known Lyman-Kutcher-Burman (LKB) model and Kallman's relative seriality
      model. Studies by Martel and coworkers on pericarditis and by Gagliardi and
      coworkers on cardiac mortality are reviewed. The anatomical and functional
      definition of the heart represents a key issue in modeling, as it affects
      strongly the dosimetrical data to be used as input data in the models. Several
      treatment strategies to decrease heart irradiation, based on models and/or based
      on dose-distribution evaluations, are reviewed. It is concluded that left-sided
      breast cancer patients should always be 3-dimensional (3D) dose planned.

PMID- 11447580
TI  - Partial irradiation of the parotid gland.
AB  - Recent efforts to reduce xerostomia associated with irradiation (RT) of head and
      neck cancer include the use of conformal and intensity-modulated RT (IMRT) to
      partly spare the major salivary glands, notably the parotid glands, from a high
      radiation dose while treating adequately all the targets at risk of disease.
      Knowledge of the dose-volume-response relationships in the salivary glands would
      determine treatment planning goals and facilitate optimization of the RT plans.
      Recent prospective studies of salivary flows following inhomogeneous irradiation
      of the parotid glands have utilized dose-volume histograms (DVHs) and various
      models to assess these relationships. These studies found that the mean dose to
      the gland is correlated with the reduction of the salivary output. This is
      consistent with a pure parallel architecture of the functional subunits (FSUs) of
      the salivary glands. The range of the mean doses, which have been found in these
      studies to cause significant salivary flow reduction is 26 to 39 Gy.

PMID- 11447581
TI  - Partial irradiation of the liver.
AB  - The use of three-dimensional radiotherapy (RT) and the prospective follow-up of
      patients for radiation-induced liver disease (RILD) have led to a more
      quantitative understanding of the partial organ tolerance of the liver compared
      with previous estimates based on clinical judgment alone. Parameters of both the
      Lyman normal tissue complication probability (NTCP) model and a local damage
      organ injury (D-I) NTCP model have been fit to clinical data from patients who
      have received hepatic radiation. Based on analyses of over 180 patients, the
      liver exhibits a large volume effect and a low threshold volume for RILD. Mean
      liver dose is associated with RILD, and no cases of RILD have been reported in
      patients with a mean liver dose of less than 31 Gy. Most recent estimates of the
      partial liver tolerance to RT suggest that if less than 25% of the normal liver
      is treated with RT, then there may be no upper limit on dose associated with
      RILD. Estimates of the liver doses associated with a 5% risk of RILD for uniform
      irradiation of one third, two thirds, and the whole liver are 90 Gy, 47 Gy, and
      31 Gy, respectively.

PMID- 11447582
TI  - Partial irradiation of the lung.
AB  - Many factors like fractionation, overall treatment time, and patient specific
      aspects are important when studying and quantifying the effects of partial lung
      irradiation. The local reactions of lung tissue to irradiation are described with
      regard to the dose-volume effect. Different models that are used to predict the
      incidence of radiation pneumonitis and the influence of irradiation on the
      overall lung function are discussed. The easy-to-calculate mean lung dose (MLD)
      and the volume irradiated to 20 Gy (V20) can both be used to predict the
      incidence of radiation pneumonitis. These parameters represent 2 extremes in
      underlying local dose-effect relations for radiation pneumonitis. However,
      clinically applied treatment plans show a high correlation between the V20 and
      the MLD, so that the decision for the "best" underlying local dose-effect
      relation should be based on the analysis of additional patient data. Dose
      escalation studies and multi-center co-operation will create more possibilities
      to investigate all confounding factors concerning lung irradiation.

PMID- 11447583
TI  - Partial irradiation of the brain.
AB  - Late radiation injury is the main dose-limiting factor for radiotherapy of tumors
      of the central nervous system (CNS). Clinical experience as well as analyses of
      complication data, both for brain necrosis and for changes in neuroimaging after
      radiosurgery, suggest a pronounced volume effect in the brain. However, the
      relationships of dose and volume to complications after irradiation of lesions in
      the brain have yet to be quantitatively assessed. The quantification of volume
      effects and the modeling of normal tissue response to partial organ irradiation
      of the brain are particularly demanding because of the highly differentiated and
      complex structure of the brain and the variety of endpoints after radiotherapy
      for CNS diseases. This article summarizes the existing clinical data that
      demonstrate a volume effect in the brain and the current state of knowledge
      regarding the modeling of complications following partial irradiation of the
      brain.

PMID- 11447584
TI  - TrkB-like immunoreactivity is present on geniculocortical afferents in layer IV
      of kitten primary visual cortex.
AB  - Exogenous administration of the neurotrophins brain-derived neurotrophic factor
      (BDNF) or neurotrophin-4/5 (NT-4/5), or blockade of their endogenous actions,
      have been reported to affect the anatomic organization and physiological
      responses of neurons in developing mammalian primary visual cortex. Experimental
      alteration of levels of these neurotrophic factors can also influence the
      morphology of the geniculocortical afferents that project from the lateral
      geniculate nucleus (LGN) to primary visual cortex. BDNF and NT-4/5 are ligands of
      the TrkB tyrosine kinase receptor. Although multiple populations of cortical
      neurons express TrkB, it is not known whether geniculocortical afferents express
      this receptor on their axon branches in visual cortex. We have anatomically
      labeled geniculocortical afferents of postnatal day 40 kittens with the
      anterograde neuronal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and
      performed double-label immunofluorescence with a panel of anti-TrkB antibodies.
      Confocal microscopy and object-based colocalization analysis were used to measure
      levels of TrkB-like immunoreactivity (IR) on geniculocortical afferents in layer
      IV of primary visual cortex. By using a conservative analysis involving a
      comparison of measured colocalization with the amount of colocalization expected
      based on random overlap of TrkB puncta and PHA-L--labeled afferents, 3 of 5 anti
      TrkB antibodies tested showed significant colocalization with the
      geniculocortical axons. Results for the other two antibodies were indeterminate.
      The indices obtained for colocalization of TrkB and geniculocortical afferents
      were also compared with the equivalent index obtained for GAD65, a protein that
      has a similar overall expression pattern to that of TrkB but is not expressed on
      geniculocortical axons. This analysis indicated that TrkB was present on
      geniculocortical axons for all five TrkB antibodies tested. TrkB-like IR was also
      observed on neuronal somata in the LGN. These results indicate that TrkB
      receptors on geniculocortical afferents are potential mediators of the actions of
      BDNF and NT-4/5 in developing visual cortex.

PMID- 11447585
TI  - GDNF gene delivery to injured adult CNS motor neurons promotes axonal growth,
      expression of the trophic neuropeptide CGRP, and cellular protection.
AB  - Glial-cell-line--derived neurotrophic factor (GDNF) has been identified as a
      potent survival and differentiation factor for several neuronal populations in
      the central nervous system (CNS), but to date, distinct effects of GDNF on motor
      axon growth and regeneration in the adult have not been demonstrated. In the
      present study, ex vivo gene delivery was used to directly examine whether GDNF
      can influence axonal growth, expression of neuronal regeneration-related genes,
      and sustain the motor neuronal phenotype after adult CNS injury. Adult Fischer
      344 rats underwent unilateral transections of the hypoglossal nerve, followed by
      intramedullary grafts of fibroblasts genetically modified to secrete GDNF.
      Control animals received lesions and grafts of cells expressing a reporter gene.
      Two weeks later, GDNF gene delivery (1) robustly promoted the growth of lesioned
      hypoglossal motor axons, (2) altered the expression and intracellular trafficking
      of the growth-related protein calcitonin gene-related peptide (CGRP), and (3)
      significantly sustained the cholinergic phenotype in 84 +/- 6% of hypoglossal
      neurons compared with 39 +/- 6% in control animals (P < 0.001). This is the first
      neurotrophic factor identified to increase the in vivo expression of the trophic
      peptide CGRP and the first report that GDNF promotes motor axonal growth in vivo
      in the adult CNS. Taken together with previous in vitro studies, these findings
      serve as the foundation for a model wherein GDNF and CGRP interact in a paracrine
      manner to regulate neuromuscular development and regeneration.

PMID- 11447586
TI  - Development of the perforating pathway: an ipsilaterally projecting pathway
      between the medial septum/diagonal band of Broca and the cingulate cortex that
      intersects the corpus callosum.
AB  - The perforating pathway (PFP) intersects the corpus callosum perpendicularly at
      the midline in the dorsoventral axis. Therefore axons in either the PFP or the
      corpus callosum make different axonal guidance decisions in the same anatomical
      region of the developing cortical midline. The mechanisms underlying these axonal
      choices are not known. To begin to identify these guidance mechanisms, we
      characterized the development of these two pathways in detail. The development of
      the corpus callosum and its pioneering projections has been described elsewhere
      (Shu and Richards [2001] J. Neurosci. 21:2749--2758; Rash and Richards [2001] J.
      Comp. Neurol. 434:147--157). Here we examine the development, origins, and
      projections of axons that make up the PFP. The majority of axons within the PFP
      originate from neurons in the medial septum and diagonal band of Broca complex.
      These neurons project in a topographic manner to the cingulate cortex. In
      contrast to previous reports, we find that a much smaller projection originating
      from the cingulate cortex also contributes to this pathway. The pioneering
      projections of the PFP and the corpus callosum arrive at the corticoseptal
      boundary at around the same developmental stage. These findings show that
      ipsilaterally projecting PFP axons and contralaterally projecting callosal axons
      make distinct guidance decisions at the same developmental stage when they reach
      the corticoseptal boundary.

PMID- 11447587
TI  - Cannabinoid receptors are absent in insects.
AB  - The endocannabinoid system exerts an important neuromodulatory role in mammals.
      Knockout mice lacking cannabinoid (CB) receptors exhibit significant morbidity.
      The endocannabinoid system also appears to be phylogenetically ancient--it occurs
      in mammals, birds, amphibians, fish, sea urchins, leeches, mussels, and even the
      most primitive animal with a nerve network, the Hydra. The presence of CB
      receptors, however, has not been examined in terrestrial invertebrates (or any
      member of the Ecdysozoa). Surprisingly, we found no specific binding of the
      synthetic CB ligands [(3)H]CP55,940 and [(3)H]SR141716A in a panel of insects:
      Apis mellifera, Drosophila melanogaster, Gerris marginatus, Spodoptera
      frugiperda, and Zophobas atratus. A lack of functional CB receptors was confirmed
      by the inability of tetrahydrocannabinol (THC) and HU210 to activate G-proteins
      in insect tissues, utilizing a guanosine-5'-O-(3-[(35)]thio)-triphosphate (GTP
      gamma S) assay. No orthologs of human CB receptors were located in the Drosophila
      genome, nor did we find orthologs of fatty acid amide hydrolase. This loss of CB
      receptors appears to be unique in the field of comparative neurobiology. No other
      known mammalian neuroreceptor is understood to be missing in insects. We
      hypothesized that CB receptors were lost in insects because of a dearth of
      ligands; endogenous CB ligands are metabolites of arachidonic acid, and insects
      produce little or no arachidonic acid or endocannabinoid ligands, such as
      anandamide.

PMID- 11447588
TI  - Basic organization of projections from the oval and fusiform nuclei of the bed
      nuclei of the stria terminalis in adult rat brain.
AB  - The organization of axonal projections from the oval and fusiform nuclei of the
      bed nuclei of the stria terminalis (BST) was characterized with the Phaseolus
      vulgaris-leucoagglutinin (PHAL) anterograde tracing method in adult male rats.
      Within the BST, the oval nucleus (BSTov) projects very densely to the fusiform
      nucleus (BSTfu) and also innervates the caudal anterolateral area, anterodorsal
      area, rhomboid nucleus, and subcommissural zone. Outside the BST, its heaviest
      inputs are to the caudal substantia innominata and adjacent central amygdalar
      nucleus, retrorubral area, and lateral parabrachial nucleus. It generates
      moderate inputs to the caudal nucleus accumbens, parasubthalamic nucleus, and
      medial and ventrolateral divisions of the periaqueductal gray, and it sends a
      light input to the anterior parvicellular part of the hypothalamic
      paraventricular nucleus and nucleus of the solitary tract. The BSTfu displays a
      much more complex projection pattern. Within the BST, it densely innervates the
      anterodorsal area, dorsomedial nucleus, and caudal anterolateral area, and it
      moderately innervates the BSTov, subcommissural zone, and rhomboid nucleus.
      Outside the BST, the BSTfu provides dense inputs to the nucleus accumbens, caudal
      substantia innominata and central amygdalar nucleus, thalamic paraventricular
      nucleus, hypothalamic paraventricular and periventricular nuclei, hypothalamic
      dorsomedial nucleus, perifornical lateral hypothalamic area, and lateral
      tegmental nucleus. Moderately dense inputs are found in the parastrial, tuberal,
      dorsal raphe, and parabrachial nuclei and in the retrorubral area, ventrolateral
      division of the periaqueductal gray, and pontine central gray. Light projections
      end in the olfactory tubercle, lateral septal nucleus, posterior basolateral
      amygdalar nucleus, supramammillary nucleus, and nucleus of the solitary tract.
      These and other results suggest that the BSTov and BSTfu are basal telencephalic
      parts of a circuit that coordinates autonomic, neuroendocrine, and ingestive
      behavioral responses during stress.

PMID- 11447589
TI  - Neurotrophism without neurotropism: BDNF promotes survival but not growth of
      lesioned corticospinal neurons.
AB  - Neurotrophic factors exert many effects on the intact and lesioned adult central
      nervous system (CNS). Among these effects are prevention of neuronal death
      (neurotrophism) and promotion of axonal growth (neurotropism) after injury. To
      date, however, it has not been established whether survival and axonal growth
      functions of neurotrophins can be independently modulated in injured adult
      neurons in vivo. To address this question, the ability of brain-derived
      neurotrophic factor (BDNF) to influence corticospinal motor neuronal survival and
      axonal growth was examined in two injury paradigms. In the first paradigm, a
      survival assay, adult Fischer 344 rats underwent subcortical lesions followed by
      grafts to the lesion cavity of syngenic fibroblasts genetically modified to
      secrete high amounts BDNF or, in control subjects, the reporter gene green
      fluorescent protein. In control subjects, only 36.2 +/- 7.0% of the retrogradely
      labeled corticospinal neurons survived the lesion, whereas 89.8 +/- 5.9% (P <
      0.001) of the corticospinal neurons survived in animals that received BDNF
      secreting grafts. However, in an axonal growth assay, BDNF-secreting cell grafts
      that were placed into either subcortical lesion sites or sites of thoracic spinal
      cord injury failed to elicit corticospinal axonal growth. Despite this lack of a
      neurotropic effect on lesioned corticospinal axons, BDNF-secreting cell grafts
      placed in the injured spinal cord significantly augmented the growth of other
      types of axons, including local motor, sensory, and coerulospinal axons.
      Immunolabeling for tyrosine kinase B (trkB) demonstrated that BDNF receptors were
      present on corticospinal neuronal somata and apical dendrites but were not
      detected on their projecting axons. Thus, single classes of neurons in the adult
      CNS appear to exhibit disparate survival and growth sensitivity to neurotrophic
      factors, potentially attributable at least in part to differential trafficking of
      neurotrophin receptors. The possibility of tropic/trophic divergence must be
      considered when designing strategies to promote CNS recovery from injury.

PMID- 11447590
TI  - Localization of kainate receptors at the cone pedicles of the primate retina.
AB  - In the macaque monkey retina cone pedicles, the output synapses of cone
      photoreceptors, contain between 20 and 45 ribbon synapses (triads), which are the
      release sites for glutamate, the cone transmitter. Several hundred postsynaptic
      dendrites contact individual cone pedicles, and we studied the glutamate
      receptors expressed and clustered at these contacts, particularly the kainate
      receptor subunits GluR5, GluR6/7, and KA2. Pre- and postembedding
      immunocytochemistry and electron microscopy were used to localize GluR5 and
      GluR6/7 to specific synaptic contacts at the cone pedicle base. The GluR5 subunit
      was aggregated at bipolar cell flat contacts. The GluR6/7 subunit was aggregated
      at bipolar cell flat contacts and at the desmosome-like junctions formed by
      horizontal cell processes underneath the cone pedicles. KA2 immunoreactivity was
      observed at the invaginating dendritic tips of ON-cone and rod bipolar cells,
      which we interpret as a cross-reactivity of the KA2 antiserum with some other,
      unknown protein of the monkey retina. Kainate receptors are preferentially
      expressed by OFF-cone bipolar cells and to a lesser extent by horizontal cells.
      We also performed double-labeling experiments with the ribbon-specific marker
      bassoon and with antibodies against GluR5 and GluR6/7 in order to define the
      position of the flat bipolar cell contacts with respect to the triads. There was
      a tendency of GluR6/7 clusters to represent triad-associated contacts, whereas
      GluR5 clusters represented non-triad-associated contacts. The GluR5 and GluR6/7
      subunits were clustered at different bipolar cell contacts. We studied a possible
      cone-selective expression of the kainate receptor subunits by double labeling
      cone pedicles for the S-cone opsin and for the different receptor subunits. We
      observed a reduced expression of both GluR5 and GluR6/7 at the S-cone pedicles.
      The reduced expression of GluR6/7 was analyzed in more detail and it appears to
      be a consequence of a horizontal cell-specific expression: H1 horizontal cells
      express GluR6/7, whereas H2 horizontal cells, which preferentially innervate S
      cones, show no expression of GluR6/7.

PMID- 11447591
TI  - Retina of Bouton's skink (Reptilia, Scincidae): visual cells, fovea, and
      ecological constraints.
AB  - Bouton's skink, Cryptoblepharus boutonii africanus, is a small, diurnal lizard
      living on outcrops along the coast of East Africa under high ambient light
      intensities. It is characterized by relatively large eyes (maximal diameter about
      2 mm), with immovable eyelids forming a transparent spectacle and with a
      virtually constant pupil diameter. The single fovea in the central retina is well
      developed, with a clearly defined pit, which is relatively deep but not funnel
      shaped. The foveal pit is not devoid of the outer nuclear and outer plexiform
      layers; only the main part of the inner nuclear layer is displaced laterally,
      resulting in a pit with gradual sloping towards its edges. Thus, the fovea
      appears to be concaviclivate, as in the eyes of lacertids, varanids, and
      gekkonids. The central position of the foveae in these laterally placed scincid
      eyes corresponds with monocular fixation, e.g., of detected prey. C. boutonii has
      a pure-cone retina containing single and double visual cells. The latter consist
      of two cells of unequal sizes. Yellowish oil droplets are present in single cones
      and the minor members of the double cones in all retinal regions. The visual
      cells of the different retinal regions do not differ in the ultrastructure of
      their components but differ considerably in size. The outer segments of the
      foveal cones are twice as long as those of the peripheral cones. Except for the
      pedicles, the diameters of the components of the visual cells decrease towards
      the fovea, resulting in an increase in visual acuity.

PMID- 11447592
TI  - Chemically and morphologically identifiable glomeruli in the rat olfactory bulb.
AB  - Primary olfactory neurons that express the same odorant receptor are distributed
      mosaically throughout the olfactory neuroepithelium lining the nasal cavity, yet
      their axons converge and form discrete glomeruli in the olfactory bulb. We
      previously proposed that cell surface carbohydrates mediate the sorting out and
      selective fasciculation of primary olfactory axons en route to glomeruli. If this
      were the case, then axons that terminate in the same glomerulus would express the
      same complement of cell surface carbohydrates. In this study, we examined the
      expression of a novel carbohydrate (NOC-3) on neural cell adhesion molecule in
      the adult rat olfactory system. NOC-3 was expressed by a subset of neurons
      distributed throughout the olfactory neuroepithelium. The axons of these neurons
      entered the nerve fiber layer and terminated in a subset of glomeruli. It is
      interesting to note that we identified three unusually large glomeruli in the
      lateral, ventrolateral, and ventromedial olfactory bulb that were innervated by
      axons expressing NOC-3. NOC-3-expressing axons sorted out and fasciculated into
      discrete fascicles prior to entering these glomeruli. Each of these glomeruli was
      in a topographically fixed position in the olfactory bulbs of the same animal as
      well as in different animals, and their lengths were approximately 10% of the
      total length of the bulb. They could be identified reliably by both their
      topographical position and their unique morphology. These results reveal that
      axons expressing the same cell surface carbohydrates consistently target the same
      topographically fixed glomeruli, which supports a role for these molecules in
      axon navigation in the primary olfactory nerve pathway.

PMID- 11447593
TI  - Fundamental differences between the thalamocortical recipient layers of the cat
      auditory and visual cortices.
AB  - In visual and somatosensory cortices of several species, spiny stellate cells in
      layer 4 are the first elements in signal processing where thalamic information is
      integrated and emergent receptive field properties are generated and sent on to
      more superficial cortical layers. In vivo and in vitro experiments have provided
      important information about how the anatomy and physiology of these cells and
      this layer fit into the functional cortical circuitry. No such data exist for the
      auditory cortex but are requisite if we are to understand whether ideas about
      information processing in one sensory cortical area can be generalized to
      another. Accordingly, we used in vitro slices from which to record and labeled
      cells in the middle layers of the cat auditory and visual cortices to compare
      basic anatomical and physiological features of cells recovered in similar layers
      using the same methods. Our results demonstrate a striking difference in a basic
      characteristic of two primary sensory cortical areas. In the visual cortex, spiny
      stellate cells predominate, receive short-latency synaptic inputs, and project to
      supergranular layers. No such spiny stellate population is encountered in the
      middle layers of the auditory cortex. Spiny cells that are not stellate or
      pyramidal are occasionally encountered but, as a group, do not display consistent
      anatomical or physiological features that might allow them to function as
      auditory cortical versions of the visual spiny stellates. Rather, pyramidal cells
      in the lower half of layer 3 and layer 4 appear to have assumed this role.

PMID- 11447594
TI  - Yeast 14-3-3 proteins.

PMID- 11447595
TI  - The GDI1 genes from Kluyveromyces lactis and Pichia pastoris: cloning and
      functional expression in Saccharomyces cerevisiae.
AB  - The nucleotide sequences of 2.8 kb and 2.9 kb fragments containing the
      Kluyveromyces lactis and Pichia pastoris GDI1 genes, respectively, were
      determined. K. lactis GDI1 was found during sequencing of a genomic library
      clone, whereas the P. pastoris GDI1 was obtained from a genomic library by
      complementing a Saccharomyces cerevisiae sec19-1 mutant strain. The sequenced DNA
      fragments contain open reading frames of 1338 bp (K.lactis) and 1344 bp (P.
      pastoris), coding for polypeptides of 445 and 447 residues, respectively. Both
      sequences fully complement the S. cerevisiae sec19-1 mutation. They have high
      degrees of homology with known GDP dissociation inhibitors from yeast species and
      other eukaryotes.

PMID- 11447596
TI  - Characterization of a Schizosaccharomyces pombe mutant deficient in UDP-galactose
      transport activity.
AB  - In fission yeast, Schizosaccharomyces pombe, the carbohydrate components of the
      cell wall consist of galactomannan, unlike in Saccharomyces cerevisiae. We
      previously found that the disruption of gms1+, a gene encoding the UDP-galactose
      transporter required for the synthesis of galactomannan, led to the complete
      defect of cell surface galactosylation in Sz. pombe. The Deltagms1 strain is
      therefore useful for the analysis of physiological properties of galactose
      residues in Sz. pombe. The deletion strain of gms1+ was viable; however, itshowed
      an aberrant cell morphology and increased sensitivities to digestion with beta
      glucanase and to various drugs, such as hygromycin B, sodium orthovanadate and
      Calcofluor white. A reduction of galactomannan layers of the cell wall in the
      Deltagms1 strain was observed by scanning and transmission electron microscopic
      analyses. The addition of osmotic stabilizer suppressed the morphologic defect of
      the Deltagms1 cells, while other phenotypes were weakly suppressed. The Deltagms1
      (h90) strain was incapable of sexual conjugation during nutritional starvation.
      These results suggest that the cell surface galactosylation is required not only
      for non-sexual flocculation but also for sexual conjugation in Sz. pombe.

PMID- 11447597
TI  - Molecular cloning of CaYRB1, the Candida albicans RanBP1/YRB1 homologue.
AB  - The yeast Ran binding protein 1 (Yrb1p) is a small protein of 23 kDa that is
      highly conserved among eukaryotes. It stimulates the GTPase activity of Gsp1p in
      the presence of the GTPase activating protein Rna1p. In addition to its role in
      nucleocytoplasmic transport of macromolecules, YRB1/RanBP1 could be involved in
      the regulation of microtubules structure and dynamics. Since microtubules are
      tightly associated with morphological changes, we have been interested to study
      the role and function of YRB1 in the pathogenic fungus Candida albicans, where
      there is regulated change in cellular morphology. The gene product of CaYRB1
      encodes a 212 amino acid protein displaying 73% homology to the S. cerevisiae
      homologue. The bacterially expressed gene product has an apparent molecular
      weight of 35.7 kDa. We show that it can complement a S. cerevisiae yrb1 null
      mutant and that its mRNA does not appear to be regulated in response to
      conditions inducing morphological changes in C. albicans.

PMID- 11447598
TI  - Hexokinase PII: structural analysis and glucose signalling in the yeast
      Saccharomyces cerevisiae.
AB  - Hexokinase PII (Hxk2) is a yeast glucose phosphorylating enzyme that, besides its
      role in glycolysis, seems to have an additional role in glucose signalling. To
      study the domains in Hxk2 that may participate in this latter process, we have
      constructed 11 mutant alleles using site-directed mutagenesis. Six of them were
      clustered charged-to-alanine mutants in which clusters of charged residues were
      changed to alanine residues. Two of them contained substitutions in Ser15 to
      either alanine or glutamic acid and three of them had deletions at either the N
      terminus or the C-terminus of the protein. In most of them, the catalytic
      activity correlated directly with their functionality in glucose signalling.
      However, we found two mutants (Delta1-15 and Delta476-486) that, having low
      catalytic activity, were still fully functional in glucose signalling. This may
      indicate that other factors and not just the catalytic activity of the enzyme may
      be important for the functionality of the protein in glucose signalling.

PMID- 11447599
TI  - Functional analysis of six ORFs from Saccharomyces cerevisiae chromosome IV: two
      spored asci produced by disruptant of YDR027c and strain-dependent DNA
      heterogeneity around YDR036c.
AB  - Six S. cerevisiae FY1679 heterozygous deletion mutants were made by replacing six
      open reading frames (ORFs) of the chromosome IV right arm with kanMX4 selection
      marker. Haploid and homozygous diploid deletion mutants were obtained from
      sporulation, dissection and mating experiments. No essential genes were found.
      The basic phenotypic analysis showed that the haploid and homozygous deletants
      for the ORF YDR027c (LUV1, VSP54 or RKI1) grew slowly. The diploid homozygous
      deletants for this ORF had a low frequency of sporulation. They produced asci
      with no more than one or two haploid spores and the majority of these spores
      formed were not viable. The deletion of the other ORFs, YDR022c (CIS1), YDR030c
      (RAD28), YDR032c (PST2), YDR033w (MRH1) and YDR036c, did not change the
      phenotypes tested in strain FY1679 or the first four ORFs in strain CEN.PK2. This
      work showed some differences in the DNA sequences between FY1679 and CEN.PK2: the
      regions immediately 1 kb upstream from YDR036c in these two strains are too
      different to hybridize properly, preventing deletion of YDR036c in the CEN.PK2
      background by recombination with a disruption cassette designed for FY1679. In
      addition, there are different sets of transposable elements on the other side of
      the ORF, the differences starting at about 3.5 kb downstream from YDR036c.

PMID- 11447600
TI  - Yeast Lrg1p acts as a specialized RhoGAP regulating 1,3-beta-glucan synthesis.
AB  - Selection of an extragenic suppressor of fks1-1154 Deltafks2, mutations in the
      catalytic subunits of yeast 1,3-beta-glucan synthase (GS) conferring temperature
      sensitivity, led to the LRG1 gene, which was originally identified as a LIM
      RhoGAP homologous gene. Mutations in the LRG1 gene restore impaired 1,3-beta
      glucan synthesis in the fks1-1154 Deltafks2 mutant as well as that in rho1-2, a
      temperature-sensitive mutant of Rho-type GTPase that functions as a regulatory
      subunit of GS. Two-hybrid analyses of Lrg1p, which contains a sequence conserved
      among Rho GTPase-activating proteins (GAPs), revealed its specific interactions
      with the active form of Rho1p. Among eight potential yeast RhoGAPs, Lrg1p is the
      only member that negatively regulates GS activity: mutations in the rest of GAPs,
      including bem2, Deltabem3, Deltasac7, Deltabag7, Deltarga1, Deltarga2 and
      Deltargd1, do not suppress impairment of 1,3-beta-glucan synthesis. Analyses of
      Mpk1p phosphorylation revealed the inability of Lrg1p to regulate the Pkc1p-MAP
      kinase cascade, a distinct Rho1p-regulating signalling pathway known to be
      affected by the GAPs, Bem2p and Sac7p. Thus, different groups of Rho1p GAPs
      control the activity of different Rho1p-effector proteins.

PMID- 11447601
TI  - Genome organization of the linear cytoplasmic element pPE1B from Pichia
      etchellsii.
AB  - The linear cytoplasmic element pPE1B from Pichia etchellsii CBS2011 (synonym
      Debaryomyces etchellsii) was totally sequenced. It consists of 12835 bp and has a
      remarkable high A+T content of 77.3%. The termini of pPE1B were found to consist
      of inversely orientated identical nucleotide repetitions 161 base pairs long, to
      which proteins are probably covalently linked at the 5' ends. Ten putative genes
      (open reading frames, ORFs) were identified, covering 96.5% of the total
      sequence. The predicted polypeptides correspond to proteins encoded by ORFs 2-11
      of the linear plasmids pGKL2 of Kluyveromyces lactis and pSKL of Saccharomyces
      kluyveri. ORF1, existing on both latter elements, is lacking on pPE1B. An
      upstream conserved sequence motif (UCS) is located at the expected distance from
      the start codon of each of the 10 ORFs. As the arbitrarily chosen UCS6 was able
      to drive expression of a reporter gene in the heterologous pGKL-encoded killer
      system of K. lactis, extranuclear promoter function is probable. The almost
      congruent genome organization of pPE1B and other autonomous linear yeast plasmids
      sequenced so far, i.e. pGKL2 and pSKL, suggests a common, presumably viral,
      ancestor.

PMID- 11447602
TI  - Malo-ethanolic fermentation in grape must by recombinant strains of Saccharomyces
      cerevisiae.
AB  - Recombinant strains of Saccharomyces cerevisiae with the ability to reduce wine
      acidity could have a significant influence on the future production of quality
      wines, especially in cool climate regions. L-Malic acid and L-tartaric acid
      contribute largely to the acid content of grapes and wine. The wine yeast S.
      cerevisiae is unable to effectively degrade L-malic acid, whereas the fission
      yeast Schizosaccharomyces pombe efficiently degrades high concentrations of L
      malic acid by means of a malo-ethanolic fermentation. However, strains of Sz.
      pombe are not suitable for vinification due to the production of undesirable off
      flavours. Heterologous expression of the Sz. pombe malate permease (mae1) and
      malic enzyme (mae2) genes on plasmids in S. cerevisiae resulted in a recombinant
      strain of S. cerevisiae that efficiently degraded up to 8 g/l L-malic acid in
      synthetic grape must and 6.75 g/l L-malic acid in Chardonnay grape must.
      Furthermore, a strain of S. cerevisiae containing the mae1 and mae2 genes
      integrated in the genome efficiently degraded 5 g/l of L-malic acid in synthetic
      and Chenin Blanc grape musts. Furthermore, the malo-alcoholic strains produced
      higher levels of ethanol during fermentation, which is important for the
      production of distilled beverages.

PMID- 11447603
TI  - Molecular cloning of the RPS0 gene from Candida tropicalis.
AB  - The Saccharomyces cerevisiae RPS0 A and B genes encode proteins essential for
      maturation of the 40S ribosomal subunit precursors. We have isolated a homologue
      of the RPS0 gene from Candida tropicalis, which we named CtRPS0. The C.
      tropicalis RPS0 encodes a protein of 261 amino acid residues with a predicted
      molecular weight of 28.65 kDa and an isoelectric point of 4.79. CtRps0p displays
      significant amino acid sequence homology with Rps0p from C. albicans, S.
      cerevisiae, Neurospora crassa, Schizosaccharomyces pombe, Pneumocystis carinii
      and higher organisms, such as human, mouse and rat. CtRPS0 on a high copy number
      vector can complement the lethal phenotype linked to the disruption of both RPS0
      genes in S. cerevisiae. Southern blot analysis suggests that CtRPS0 is present at
      a single locus within the C. tropicalis genome.

PMID- 11447604
TI  - Cloning and characterization of a LON gene homologue from the human pathogen
      Paracoccidioides brasiliensis.
AB  - A LON gene homologue from the human pathogen Paracoccidioides brasiliensis
      (PbLON) has been cloned, sequenced and characterized. It encodes a putative ATP
      dependent proteinase Lon, which in Saccharomyces cerevisisae (PIM1) is a heat
      inducible protein involved in the degradation of abnormal or short-lived proteins
      in the mitochondria. The PbLON ORF is within a 3369 bp fragment interrupted by
      two introns located in the 3'segment. The 5' and 3' regions flanking the ORF
      contain sequences which resemble known transcription elements. Several
      transcription binding factor motifs have also been found, including sites for
      heat shock/stress response and nitrogen control. The deduced protein consists of
      1063 residues containing a mitochondrial import signal at the N-terminus and
      conserved ATP-binding (GPPGVGKT) and serine catalytic (KDGPSAG) sites. It shares
      high identity with Lon homologues from S. cerevisiae (73%), Homo sapiens (62%)
      and Escherichia coli (56%). In P. brasiliensis, an MDJ1 putative gene has also
      been partially sequenced adjacent to PbLON, possibly sharing divergently
      orientated promoter elements. This chromosomal organization is interesting, since
      Mdj1p is a heat shock chaperone essential for substrate degradation by PIM1 in
      yeast.

PMID- 11447606
TI  - Current awareness on yeast.

PMID- 11447605
TI  - Molecular cloning and sequence analysis of the Zygosaccharomyces rouxiiLEU2 gene
      encoding a beta-isopropylmalate dehydrogenase.
AB  - A DNA fragment carrying the LEU2 gene of osmotolerant yeast Zygosaccharomyces
      rouxii was isolated. The sequenced DNA fragment (2630 bp) contained two ORFs; one
      of them (1086 bp long, predicting a protein of 362 amino acids) shared a high
      degree of similarity with LEU2 genes of other yeast species. The cloned DNA
      fragment fully complemented the leu2 mutations of Saccharomyces cerevisiae and Z.
      rouxii.

PMID- 11447607
TI  - Context and health outcomes.

PMID- 11447608
TI  - Experiments with insulin.

PMID- 11447609
TI  - More interest in AIDS drug access plan.

PMID- 11447610
TI  - Don't homogenize, synchronize.
AB  - To be more responsive to customers, companies often break down organizational
      walls between their units--setting up all manner of cross-business and cross
      functional task forces and working groups and promoting a "one-company" culture.
      But such attempts can backfire terribly by distracting business and functional
      units and by contaminating their strategies and processes. Fortunately, there's a
      better way, says the author. Rather than tear down organizational walls, a
      company can make them permeable to information. It can synchronize all its data
      on products, filtering the information through linked databases and applications
      and delivering it in a coordinated, meaningful form to customers. As a result,
      the organization can present a single, unified face to the customer--one that can
      change as market conditions warrant--without imposing homogeneity on its people.
      Such synchronization can lead not just to stronger customer relationships and
      more sales but also to greater operational efficiency. It allows a company, for
      example, to avoid the high costs of maintaining many different information
      systems with redundant data. The decoupling of product control from customer
      control in a synchronized company reflects a fundamental fact about business:
      While companies have to focus on creating great products, customers think in
      terms of the activities they perform and the benefits they seek. For companies,
      products are ends, but for customers, products are means. The disconnect between
      how customers think and how companies organize themselves is what leads to
      inefficiencies and missed opportunities, and that's exactly the problem that
      synchronization solves. Synchronized companies can get closer to customers,
      sustain product innovation, and improve operational efficiency--goals that have
      traditionally been very difficult to achieve simultaneously.

PMID- 11447611
TI  - Taking the stress out of stressful conversations.
AB  - Stressful conversations are unavoidable in life. In business, they can run the
      gamut from firing a subordinate to, curiously enough, receiving praise. But
      whatever the context, stressful conversations carry a heavy emotional load.
      Indeed, stressful conversations cause such anxiety that most people simply avoid
      them. Yet it can be extremely costly to dodge issues, appease difficult people,
      and smooth over antagonisms; avoidance usually only worsens a problem or a
      relationship. Using vivid examples of the three basic stressful conversations
      that people bump up against most often in the workplace, the author explains how
      managers can improve those interactions unilaterally. To begin with, they should
      approach the situations with greater self-awareness. Awareness building is not
      about endless self-analysis; much of it simply involves making tacit knowledge
      about oneself more explicit. It is important for those who are vulnerable to
      hostility, for example, to know how they react to it. Do they clam up or do they
      retaliate? Knowing how you react in a stressful situation will teach you a lot
      about your trouble areas and can help you master stressful situations. The author
      also recommends rehearsing difficult conversations in advance to fine-tune your
      phrasing and tone. And the best way to keep from being thrown off balance by
      difficult conversations that crop up unexpectedly is to develop a few hip-pocket
      phrases that you can pull out on the spot. We all know from past experience what
      kinds of conversations and people we handle badly. The trick is to have prepared
      conversational tactics to address those situations.

PMID- 11447612
TI  - Five strategies of successful part-time work.
AB  - Nearly one in ten professionals now works part-time. But all too often, part-time
      work creates as many problems as it solves. At best, many part-timers work more
      hours than they intended. At worst, they see their importance to their
      organizations dwindle. Two generations have wrestled with such arrangements, and
      today some part-time professionals have found ways to overcome the challenges,
      with shining results. Drawing on two years of research investigating part-time
      engineers, financial analysts, IT specialists, and consultants, the authors
      present five strategies used by successful part-timers to make their unique
      position work for themselves and their companies. To begin with, successful part
      time professionals take pains to make their work-life priorities, their
      schedules, and their plans for the future transparent to the organization.
      Second, they broadcast the business case for their arrangement, being careful to
      demonstrate that the arrangement has not disrupted the business and may even have
      a positive impact. Third, they establish routines to protect their time at work
      and rituals to protect their time at home. Fourth, they cultivate champions in
      senior management who protect them from skeptics and advocate for their
      arrangements up and down the ranks. And last, they gently but firmly remind their
      colleagues that, despite their part-time status, they're still major players in
      the organization who cannot be ignored. Taken together, these strategies not only
      help the part-timer deal with the organization but also make the organization
      itself more receptive to the possibilities of part-time work.

PMID- 11447613
TI  - Tread lightly through these accounting minefields.
AB  - In the current economic climate, there is tremendous pressure--and personal
      incentive for managers--to report sales growth and meet investors' revenue
      expectations. As a result, more companies have been issuing misleading financial
      reports, according to the SEC, especially involving game playing around earnings.
      But it's shareholders who suffer from aggressive accounting strategies; they
      don't get a true sense of the financial health of the company, and when problems
      come to light, the shares they're holding can plummet in value. How can investors
      and their representatives on corporate boards spot trouble before it blows up in
      their faces? According to the authors, they should keep their eyes peeled for
      common abuses in six areas: revenue measurement and recognition, provisions and
      reserves for uncertain future costs, asset valuation, derivatives, related party
      transactions, and information used for bench-marking performance. If a disaster
      strikes, it will most likely be in one of these accounting minefields. This
      article examines the hazards of each minefield in turn, using examples like
      Metallgesellschaft, Xerox, MicroStrategy, and Lernout & Hauspie. It also provides
      a set of questions to ask in order to determine where a company's accounting
      practices might be overly aggressive. For those whose greatest interest is in
      fairly valuing the business--not presenting it in the best possible light--these
      questions are the first line of defense against creative accounting. Accounting
      game players are adroit, but it's both foolish and dangerous, contend the
      authors, to declare oneself ignorant and hence powerless against their
      machinations. They argue that members of corporate boards need to be financially
      literate.

PMID- 11447614
TI  - While customers wait, add value.

PMID- 11447615
TI  - Should this team be saved?
AB  - As far as anyone could tell, Vigor Skin Care's star was rising, mostly on the
      strength of Ageless Vigor, its new line of enriched skin cleansers and cosmetics.
      In fact, this evening, the three employees responsible for developing the product
      line were slated to receive the parent company's highest award for performance.
      But CEO Peter Markles knew that despite the accolades, the business unit--and its
      "fearsome threesome"--had hit a rough patch in recent months. When Peter took the
      reins four years ago, Vigor Skin Care was the sleeping dog of the health-and
      beauty industry; his challenge was to rejuvenate the maturing business. He knew a
      turnaround would require equal parts discipline, politics, and creativity--so he
      pulled together a team that could address those needs. Peter relied on Sandy
      Fryda, Vigor's longtime marketing director, to help him navigate the tricky
      political waters at headquarters. And he tapped 30-year-old Josh Bartola, a
      maverick contributor to Vigor Skin Care's research group, for his independent
      spirit and new product ideas. Their all-consuming, intensely collaborative
      efforts resulted in the successful Ageless Vigor line. Then reality set in. The
      team found the day-to-day operations of manufacturing Ageless Vigor, for all
      their necessity and urgency, a bit tedious. Peter felt relegated to
      troubleshooting distribution problems. Josh was having meetings with executives
      from another division who were actively recruiting the wunderkind. And Sandy was
      simply on the verge of burnout. Tonight, at the award ceremony, there would be
      speeches and applause and toasts. But tomorrow, Peter would have to face the
      question: Should he try to salvage the Ageless Vigor team? Four commentators
      offer their advice in this fictional case study.

PMID- 11447616
TI  - Transforming a conservative company--one laugh at a time.
AB  - You wouldn't think of Brady Corporation as an obvious place in which to find a
      fun culture. This traditional Midwestern company, a manufacturer of industrial
      signs and other identification products, didn't even allow employees to have
      coffee at their desks until 1989. But when Katherine Hudson became CEO in 1994,
      she and her executive team determined that injecting some fun into the company's
      serious culture could create positive effects within the organization and
      contribute to increased performance and sales. In this article, Hudson distills
      her approach to overhauling Brady's culture into six principles of serious fun:
      More people than you might think are comfortable having fun at work; used with an
      awareness of cultural sensitivities, fun and laughter really are well-understood
      international languages; humor can help companies get through tough times; fun
      can be embodied in formal programs; spontaneous efforts at humor can also be
      effective; and encouraging fun should begin at the top. She richly illustrates
      each principle with examples. At Brady, getting people to loosen up and enjoy
      themselves has fostered a company esprit de corps and greater team camaraderie.
      It has started conversations that have sparked innovation, helped to memorably
      convey corporate messages to employees, and increased productivity by reducing
      stress, among other benefits. And the company has doubled its sales and almost
      tripled its net income and market capitalization over the past seven years.
      Brady's experience suggests that promoting fun within the workplace can lead not
      only to a robust corporate culture but also to improved business performance.

PMID- 11447617
TI  - How to win the blame game.
AB  - At some companies, people are all too quick to point fingers, leaving employees
      more concerned about avoiding blame than about achieving results. Such
      organizations, ruled by "CYA," have given blame a bum rap. David Baldwin, a
      former Major League pitcher, says blame can be a powerful and constructive force.
      It can be an effective teaching tool that helps people avoid repeating their
      mistakes. When used judiciously--and sparingly--blame can also prod people to put
      forth their best efforts, while maintaining both their confidence and their focus
      on goals. Indeed, blame can have a very positive effect when it's done for the
      right reasons. The key, then, is the way that blame is managed, which can
      influence how people make decisions and perform their jobs and ultimately affect
      the culture and character of an organization. In the course of his research on
      how Major League Baseball managers make decisions, Baldwin became fascinated by
      the subject of blame--what functions it serves and how it's best managed. His
      observations led him to identify five rules of blame, which, he says, apply to
      any organization, whether it's the LA Dodgers, General Motors, or a small start
      up. First, know when to blame--and when not to. Second, blame in private and
      praise in public. Third, realize that the absence of blame can be far worse than
      its presence. Fourth, manage misguided blame. And fifth, be aware that confidence
      is the first casualty of blame. Managers who follow these rules will use blame in
      the most positive and effective ways possible, Baldwin says. Without these rules,
      blame becomes an ever-more difficult balancing act: Too much erodes people's
      confidence, while too little hinders them from reaching their full potential.

PMID- 11447618
TI  - Managing for value. It's not just about the numbers.
AB  - In theory, value-based management programs sound seductively simple. Just adopt
      an economic profit metric, tie compensation to agreed-upon improvement targets in
      that metric, and voila! Managers and employees will start making all kinds of
      value-creating decisions. If only it were that easy. The reality is, almost half
      of the companies that have adopted a VBM metric have met with mediocre success.
      That's because, the authors contend, the successful VBM program is really about
      introducing fundamental changes to a big company's culture. Results from their
      major research project into the practice of VBM reveal that putting VBM into
      practice is far more complicated than many of its proponents make it out to be,
      requiring a great deal of patience, effort, and money. According to the authors'
      study, companies that successfully use VBM programs share five main
      characteristics. First, nearly all made explicit and public their commitment to
      shareholder value. Second, through training, they created an environment
      receptive to the changes the program would engender. Third, they reinforced that
      training with broad-based incentive systems closely tied to the VBM performance
      measures, which gave employees a sense of ownership in both the company and the
      program. Fourth, they were willing to craft major organizational changes to allow
      all their workers to make those value-creating decisions. Finally, the changes
      they introduced to the company's systems and processes were broad and inclusive
      rather than focused narrowly on financial reports and compensation. A VBM program
      is difficult and expensive. Still, the authors argue, properly applied, it will
      put your company's profitability firmly on track.

PMID- 11447619
TI  - Lead for loyalty.
AB  - The greater the loyalty a company engenders among its customers, employees,
      suppliers, and shareholders, the greater the profits it reaps. Frederick
      Reichheld, a director emeritus of Bain & Company, offers advice on improving
      loyalty that is based on more than a decade of research. Primarily, he says,
      outstanding loyalty is the direct result of the decisions and practices of
      committed top executives with personal integrity. The "loyalty leader" companies-
      those with the most impressive loyalty credentials--are a diverse group, ranging
      from Vanguard and Northwestern Mutual to Chick-fil-A, Harley-Davidson, Intuit,
      and Enterprise Rent-A-Car. But beneath their surface variations lie six
      strikingly similar relationship strategies: 1. Preach what you practice.
      Executives must preach the importance of loyalty in clear, precise, powerful
      terms. 2. Play to win-win. It's not enough that your competitors lose; your
      partners must win. There's a clear connection, for instance, between a company's
      treatment of its employees and its attitude toward customers. 3. Be picky. A
      truly humble company knows it can satisfy only certain customers, and it goes all
      out to keep them happy. Careful selection of employees also plays an important
      role. 4. Keep it simple. Great leaders understand that they must simplify rules
      for decision making. 5. Reward the right results. Many companies reward employees
      who grab short-term profits and short-change those who build long-term value and
      customer loyalty. 6. Listen hard, talk straight. Long-term relationships require
      honest, two-way communication and learning. Exemplary leaders break through the
      cynicism of the times by showing they believe that an organization thrives when
      its partners and customers do.

PMID- 11447620
TI  - The right way to be fired.
AB  - Nearly all of us will lose our jobs sometime, but is there a right way to be
      terminated? What differentiates fired employees who make the best of their
      situations from those who do not? One answer is mind-set. Many workers
      unconsciously hold a "tenure mind-set," believing in the promise of employment
      security. By contrast, other workers hold an "assignment mentality," seeing each
      job as one in a series of impermanent, career-building stepping-stones. Most
      corporate board members and CEOs have this latter mind-set and consider their
      executives to be filling terminal assignments; people who possess this mentality
      usually rebound swiftly when fired. But when employees who hold a tenure mind-set
      are suddenly fired or laid off, the authors say, they can fall into three common
      traps. Executives who have overidentified with their jobs and feel indispensable
      to their organizations get caught in the "lost identity" trap; they react to
      termination with anger and bitterness. In the "lost family" trap, employees
      possess tight-knit, emotional bonds with coworkers. When terminated, they feel
      betrayed and rejected. And finally, some introverted executives fall into the
      "lost ego" trap; they quietly retreat without negotiating fair termination
      packages and may settle for less satisfying work the next time around. To prepare
      for the eventuality of termination, the authors suggest that executives adopt the
      assignment mind-set at all times. They should keep their social networks alive,
      include a termination clause in employment contracts, and consider hiring an
      agent. If warning signs warrant, they might even volunteer to be terminated. By
      assuming control over the way they are fired, people can gain control over their
      careers.

PMID- 11447621
TI  - [Burns on the threshold of the third millenium].

PMID- 11447622
TI  - [Evaluation of prognostic factors in the burned patient].
AB  - Mortality predictive factors of burned patients are analyzed in a population of
      1929 patients by the statistical method of logistic regression. Among the
      variables studied (total burn skin area, deep burn area, superficial burn area,
      age, sex, burn location, preexisting disorders), two only, deep burn area and
      age, have been retained as predictive factors which, when associated, allow to
      classify 94.47% of the patients in either survival or death group. The prognosis
      weight of the deep burn area (SBP) is superior to that of the total burn skin
      area, yet retained in most previous studies. The superficial burn area, the
      inhalation injuries and the preexisting disorders are not factors determining
      prognosis. The F equation = e(-6.0061 + (0.0829*SBP) + (0.0443*%AGE)) resulting
      of the logistic regression, allows a direct evaluation of the death probability.
      A simple linear relation can be proposed as score of severity: IG = (2 x %SBP) +
      age. Below 80, mortality is close to zero, above mortality increases linearly up
      to 210, reaching 100%. This relation must be handled cautiously when comparing
      the severity score of two groups of patients, just as any other severity score
      that uses a linear relation with the burnt area associated or not to age.

PMID- 11447623
TI  - [Integra, a new surgical alternative for the treatment of massive burns. Clinical
      evaluation of acute and reconstructive surgery: 39 cases].
AB  - Early excision and prompt coverage in severely burned patients are the best way
      to lessen morbidity and improve survival. Repair of full-thickness burns requires
      replacement of both dermal and epidermal components of skin and treatment with
      split thickness autografts replaces both of them. But healthy skin is not
      sufficient in extensive burns. Alternative to split thickness skin grafts have
      been studied by several groups including epidermis, dermis or a complete
      replacement comprising epidermis and dermis. Because of the difficulties in
      homografts supplying, a new way was use to replace the dermis. In 1981, Yannas
      and Burke were the first to develop such a matrix. Integra is available in France
      since 1997 and was used in our service for the treatment of both acute and
      reconstructive surgery for burned patients. Twenty patients were treated for
      acute surgery. Nineteen patients were treated for reconstructive surgery of burn
      scar contractures. Fifty-one grafts of Integra were performed. Long-term final
      results seem to show that Integra improve cosmetical and functional results and
      is a new surgical alternative for the treatment of burns in the acute phase as
      well as in late surgery of deformities.

PMID- 11447624
TI  - [Facial burns in children. 197 patients].
AB  - Facial burns frequently occur in child. A total of 197 burned patients with
      facial localisation were seen during the time period (1991-1996) covered by this
      retrospective study. One hundred and sixteen patients were less than three years
      old. A quarter of the child were issued from poor social classes with nine cases
      of child abuse by burning. One hundred and thirteen injuries were performed by
      hot water or drinks. The total burn area was less than 10% in 63% of the cases.
      The average facial burned area was 4%. The cheek, the front and the chin were
      often concerned. Low limbs and trunk were unjured in all cases. 130 patients
      needed hospitalisation, and stayed in average 17.31 days at hospital. Four
      patients died from respiratory complications, all after flame injuries. Fifty two
      child needed skin split grafts. Complete cicatrisation was observed after 21 days
      of treatment in child without grafts, and after 35.65 days in child with skin
      grafts. Twenty eight patients needed physiotherapy in center. The scars had a
      correct cosmetic appearance, without retraction and inflammatory signs in 158
      child after two years. Eleven patients needed other surgical treatment. The
      authors analyse the results and insist on prevention.

PMID- 11447625
TI  - [Systemic complications of extended burns].
AB  - Burns covering more than 10% of the total body surface area (TBSA) are
      responsible for systemic perturbations which, in very severe cases, can represent
      a vital risk and, in all cases, affect the wound evolution. Among these general
      perturbations, fluid volume and electrolyte changes, leading eventually to burn
      shock, have the most dramatic consequences. Burn shock is, still to day, a vital
      risk and can also, in case of inadequate early fluid resuscitation, results in
      secondary morbidity and mortality. Fluid replacement during the very first hours
      after injury represents certainly a key point of the management of severe burn
      cases. Estimation of resuscitation fluid needs during this period is frequently
      underestimated. For adult, we recommend, during the first hour, a minimum of one
      liter for all severe injuries and two liters if the injury exceeds 50% of TBSA.
      Pulmonary injuries due to smoke inhalation are frequent, about 25% of patients
      hospitalized in burn units, and responsible for numerous death at site of house
      fires. In burn units, about 25% of hospitalized patients have pulmonary injuries
      in relation with smoke inhalation. This population has a high mortality rate
      increasing with the area of the skin injury and with age. Patients with
      inhalation injury need more resuscitation fluids, are subject to pneumonia and
      necessitate frequently mechanical ventilation. Parameters of the mechanical
      ventilation have to be choice to avoid barotrauma. Severe burn patients are
      submitted to a very high metabolic level. This can leads to a deep nutritional
      deficit responsible for an immunological suppression. It is then of major
      importance to provide an adequate nutritional support. It is also necessary to
      fight against the stress and to put the patient in a warm environment. Finally,
      infection is the most frequent and the most severe complication of burn injuries.
      Everything have to be done to avoid bacteriological contamination including
      architecture, equipment's, care procedure, nutritional support, types of wound
      dressing and most importantly surgery. Surgical procedures have to be done as
      earliest as possible to excise necrosis and cover the wound.

PMID- 11447626
TI  - [Reconstruction of facial burn sequelae].
AB  - The deep burns of the face can lead to horrible scars functionally and
      aesthetically. Treatment of these scars need several surgical interventions
      frequently and during many years. In our region we deal with this type of wounds
      as team work, multidisciplinary approach carrying out many process starting by
      emergency treatment of acute burns till the social rehabilitation. The expansion
      technique was great help in improving the shape of scars, by using the expanding
      skin as full thickness grafts. Reconstruction of the anatomical units and
      application of aesthetic techniques (like rhinoplasty, lifting, tattooing and
      autologous fat injections) participate equally in improving the quality of
      results. Many examples of treatments of burns scars are shown.

PMID- 11447627
TI  - [Breast burn sequelae. Classification and therapeutic indications].
AB  - Reconstructive surgery of post-burns scars in female (either young children or
      adults) is a frequent need in our experience. The problems is to face the
      consequences by considering the growth of mammary gland either hormonal in case
      of children or breast reconstruction as if in case of malignancy in adult female.
      Classifications of post burn scars is helpful to adapt the method of initial
      treatment, is a real need. The authors have spent part of their experience to
      treat acute case of thoracic burns, proposing classification of three types and
      specific treatment for each.

PMID- 11447628
TI  - [Correction of cervical contractures after burns with pedicled latissimus dorsi
      musculocutaneous flaps].
AB  - In selected cases of cervical retractions after burns, the authors show that
      pedicled latissimus dorsi musculocutaneous flaps may be of great help if properly
      performed. The main advantages of this method are its simplicity and the lack of
      need for a postoperative cervical splint.

PMID- 11447629
TI  - [Burn sequelae: releasing localized contractures by Z plasties].
AB  - Z plasty is a simple method to liberate brides. After recalling principles and
      indications of Z plasty, some cases reports illustrate their indications in burns
      sequela.

PMID- 11447630
TI  - Perspectives. Tasks ahead as Congress, HHS look to reshape Medicare.

PMID- 11447631
TI  - Case management--understanding the basics, making the best choice: Part 1.

PMID- 11447632
TI  - The implementation of a resource specialist role in an acute care teaching
      hospital.

PMID- 11447635
TI  - Survey of on-call systems in hospital social work departments informs change in
      compensation.

PMID- 11447636
TI  - Impact of the Veterans Millennium Health Care Act on health care social workers
      and their clients.

PMID- 11447637
TI  - AMA's doc database draws debate. Delegates spar over resolutions on privacy,
      advertising, gift limits.

PMID- 11447638
TI  - Awaiting casualties. As its own leader drops lawsuit on the AMA, healthcare
      issues take back seat.

PMID- 11447639
TI  - It still smarts. SEC settlement evokes painful memories of problems in
      Paracelsus' past.

PMID- 11447640
TI  - Blue all over. Novant Health selling HMO despite plan's profitability.

PMID- 11447641
TI  - How some fared better under PPS. Smaller nursing-home providers survived
      switchover through cost-cutting.

PMID- 11447642
TI  - Give us our PPS! Most rehab providers are impatient with delays in implementing
      payment system.

PMID- 11447643
TI  - Getting the royal treatment. Many health plans are going the extra mile for
      consumers looking for the best service for their healthcare dollar.

PMID- 11447644
TI  - Singing the bar code blues. Retail's salvation has gained only a tenuous foothold
      in healthcare purchasing.

PMID- 11447645
TI  - Kaiser Family Foundation to sell bonds.

PMID- 11447646
TI  - The power of one. Hospital threatens closure in effort to win rate hikes.

PMID- 11447647
TI  - Enforcing a new openness. JCAHO to hospitals: let patients know when their care
      hasn't met standards.

PMID- 11447648
TI  - Court gets tough on kickback charges. Upholds convictions of K.C. defendants and
      supports 'one-purpose' rule.

PMID- 11447649
TI  - Feast day. CMS will issue rules and regulations once a month.

PMID- 11447650
TI  - 'Not an appropriate use'. Did the makers of OxyContin push too hard?

PMID- 11447651
TI  - A false choice. Science should trump politics in the stem-cell debate.

PMID- 11447652
TI  - Drugs, scalpel ... and faith?

PMID- 11447653
TI  - Sweating the cost of a home gym? Instead, shed pounds for pennies.

PMID- 11447654
TI  - Water: you may already be drinking your daily fill.

PMID- 11447655
TI  - [A lost dream--service via internet?].

PMID- 11447656
TI  - [Psychosocial predictors of metabolic instability in brittle diabetes--a
      multivariate time series analysis].
AB  - The term "brittle diabetes" denotes the unstable course of an insulin-dependent
      diabetes characterised by frequent hypo- or hyperglycaemic crises. The aim of
      this study is to demonstrate empirically how psychosocial parameters interact
      with metabolic instability in a paradigmatic case of juvenile brittle diabetes.
      By means of a structured diary study, blood sugar values, moods (SAM), body
      symptoms (GBB), the daily hustle and hassle, helping therapeutic alliance (HAQ)
      and the aspects of setting were registered. Resulting time series (112 days each)
      were ARIMA-analysed by a multivariate approach. It could be shown that the mean
      variance of daily blood sugar values as an indicator of brittleness was predicted
      by moods, body complaints and by a family session as setting factor (p < 0.05,
      for corresponding predictors). Feelings of dominance preceded an increase of
      blood sugar variance, whereas depressive moods, anger and body symptoms were
      associated with metabolic instability. A family therapy session also resulted in
      an increase of the mean blood sugar variance. The model accounted for almost 30%
      of the total variance of the dependent variable (R-square-adjusted, p < 0.0001).
      The potential of multivariate time-series as a means to demonstrate psychosomatic
      interrelations is discussed. We believe that the results may also contribute to
      an empirically rooted understanding of psychodynamic processes in
      psychosomatoses.

PMID- 11447657
TI  - [Therapeutic goals in psychological medicine--state of research and development
      of a standardized self-rating instrument].
AB  - From the patient's as well as from the therapist's point of view goals of therapy
      undoubtedly play an important role in all fields of psychological medicine
      (psychiatry, psychotherapy, psychosomatic medicine). On the other hand, there is
      a substantial lack of systematic i.e. empirical studies on this issue. Giving an
      overview on the available scientific literature we start by characterising
      therapeutic goals as a secondary psychological construction. Therapeutic goals
      and their multiple associations and different aspects of psychotherapy are
      discussed. However, a variety of definitions of therapeutic goals, often
      influenced by the therapeutic orientation of the authors, make it difficult to
      integrate concepts and to compare findings. Hence, we focus on those results
      which were found in relation to general concepts, i.e. beyond specific
      theoretical approaches. Furthermore, we discuss the pros and cons of individual
      measures of therapeutic goals compared with standardised self-rating instruments.
      Finally, we underline the lack of studies on therapeutic goals in the psychiatric
      sphere and report on some results of our own pilot study on the Personal Goals
      Questionnaire in psychiatric inpatients.

PMID- 11447658
TI  - [Examination of body concept of female patients with borderline personality
      disorder].
AB  - The operationalized diagnosis of borderline personality disorder (BPD) by DSM-IV
      and ICD-10 (research criteria) is meanwhile considered as valid and reliable. A
      disturbed or inappropriate body image within the group of borderline patients is
      not assessed by these instruments. Using the "Frankfurter Korperkonzeptskalen"
      [6], we compared the body concept of 47 female patients with BPD with a group of
      patients with the diagnosis of Bulimia nervosa and with a representative sample
      of healthy subjects. We found highly significant differences between patients
      with BPD and the clinical controls as well as to the norm group. Neither
      dissociative symptoms nor sexual child abuse correlate with the extent of the
      negative body concept. Correlations between self-concept (Giessen-Test) and body
      concept as well as clinical implications of these findings are discussed.

PMID- 11447659
TI  - [Distress in parents of patients suffering from schizophrenia of affective
      disorders].
AB  - PURPOSE: The present study aims at investigating to what extent relatives of
      individuals suffering from mental illness experience caregiver burden. Hypotheses
      are formulated on the basis of stress theory and are tested on a sample of family
      members. METHOD: Relatives organised in the German and Austrian relatives'
      associations were questioned by means of mail surveys. Only parents (n = 509) of
      patients with schizophrenia or affective disorders were included in the study.
      RESULTS: The majority of those questioned expressed the opinion that the burden
      experienced through caring for the patient interferes with their own state of
      health. Among the negative consequences of care-giving cited, health burden
      ranked first, followed by restrictions in the fields of leisure,
      employment/career and finances. For the respondents, the average sum score of the
      Zerssen list of complaints [1] was clearly increased in comparison with the
      standard values for the general population. Among the symptoms cited, brooding,
      inner unrest, irritability, insomnia, fatigue as well as neck and shoulder pains
      were mentioned most frequently. No gender or diagnosis-related differences were
      found with regard to the extent of burden experienced. Interaction effects could
      be demonstrated in that fathers of schizophrenic patients differ significantly
      from mothers of schizophrenic patients as well as from fathers of children with
      affective disorders. CONCLUSIONS: Further research is called for as relatives of
      people with mental disorders seem to represent a high-risk group. On the basis of
      our data, it can be assumed that these relatives differ from the general
      population in their utilisation of medical or rehabilitation services.

PMID- 11447660
TI  - [Increased demand for psychosomatic consultation service (C-service) in a
      department of cardiology/pneumology due to psychometric screening].
AB  - The aim of the study was to test whether the routine use of the Hospital Anxiety
      and Depression Scale HADS changes the frequency and the duration of calling the
      psychosomatic C-service. 70% of all patients of the department of
      cardiology/pneumology were registered by the HADS. Psychometric screening raised
      the number of patients checked by the C-service (15.3 vs. 2.7% of all patients of
      the department; p < 0.01) and reduced the duration of the call for the C-service
      (2.7 vs. 6.4 days; p < 0.01) compared to conventional C-service. Elevated scores
      in HADS were found in 26% of the patients (21% depression, 12% anxiety).

PMID- 11447661
TI  - Meta-analysis using linear mixed models.
AB  - Psychologists often use special computer programs to perform meta-analysis. Until
      recently, this had been necessary because standard statistical packages did not
      provide procedures for such analysis. This paper introduces linear mixed models
      as a framework for meta-analysis in psychological research, using a popular
      general purpose statistical package, SAS. The approach is illustrated with three
      examples, using SAS PROC MIXED.

PMID- 11447662
TI  - A nonlinear regression approach to estimating signal detection models for rating
      data.
AB  - This paper considers a regression approach to estimating signal detection
      parameters for rating data. The methodology is based on the statistical modeling
      of ordinal data and requires only standard statistical software such as SAS
      (SAS/STAT User's Guide, 1999) for computation. The approach is more efficient
      than the current practice of extracting the parameter estimates with the use of
      specialized software and analyzing the estimates with the use of a standard
      statistical package. It greatly facilitates exploration of the effects of
      covariates on model parameters. The method is illustrated using a published data
      set from a single factor multiple-alternative perceptual task, and data from a
      more complex factorial design examining recognition memory rating data.

PMID- 11447663
TI  - Making faces: creating three-dimensional parameterized models of facial
      expression.
AB  - Previous studies of the perceptual processing and dynamics of emotional
      expression in faces have been limited by the lack of realistic yet controlled
      stimuli. The present work offers researchers a method for creating such stimuli
      for exploring these phenomena. We describe the creation of the stimuli and a
      series of experiments testing the validity of these stimuli with respect to
      emotional expressions in humans. Participants evaluated synthesized facial images
      and standardized photographs of six basic emotional expressions for intensity and
      accuracy of perceived emotion. Comparisons of these measures were qualitatively
      similar for synthesized and photographed faces. A manipulation of the magnitude
      of the synthesized expressions yielded a significant effect on the perceived
      intensity of expression. In a subsequent multidimensional scaling study, no
      systematic differences were uncovered in the derived configurations of the
      synthesized expressions and the photographs. These results are discussed in the
      context of possible future research applications.

PMID- 11447664
TI  - The evolution of inefficiency in a simulated stag hunt.
AB  - We used genetic algorithms to evolve populations of reinforcement learning (Q
      learning) agents to play a repeated two-player symmetric coordination game under
      different risk conditions and found that evolution steered our simulated
      populations to the Pareto inefficient equilibrium under high-risk conditions and
      to the Pareto efficient equilibrium under low-risk conditions. Greater degrees of
      forgiveness and temporal discounting of future returns emerged in populations
      playing the low-risk game. Results demonstrate the utility of simulation to
      evolutionary psychology.

PMID- 11447665
TI  - Argus: a suite of tools for research in complex cognition.
AB  - Argus simulates a radar-like target classification task. It was developed to
      support research in measuring and modeling cognitive work load. Argus is used in
      both single-subject and team modes. However, the Argus system is more than just a
      simulated task environment. Argus features flexible experimenter control over
      cognitive work load, as well as extensive data collection and data playback
      facilities to support the iterative nature of research in complex behaviors. In
      addition, embodied computational models interact with Argus using the same
      interface as do human subjects. In this paper, we describe these features, as
      well as the task simulation. In addition, we describe how the system has been
      used for experimentation. We conclude with a comparison of Argus with other
      complex task environments.

PMID- 11447666
TI  - Using on-line and CD-ROM database archives as an adjunct to teaching survey
      research methods.
AB  - Many undergraduate courses in research methods include a section on surveys. A
      number of practical issues can interfere with the design and implementation of
      student survey research and often preclude the completion of well-designed survey
      studies. This paper examines the use of on-line and CD-ROM databases as an
      alternative to student-designed survey instruments. Problems faced by student
      survey researchers can often be addressed by the use of such databases, rather
      than by "live" surveys. Data from experimental research collected on line are
      also available and downloadable for analysis, providing even greater flexibility
      for analysis. Advantages and problems of using archival databases in the teaching
      of survey research are considered. A brief list of databases that may be suitable
      for student research is provided, and a list of URLs, including where and how to
      obtain archives, is given.

PMID- 11447667
TI  - ACT-PRO action protocol analyzer: a tool for analyzing discrete action protocols.
AB  - This article presents a top-down approach for analyzing sequential events in
      behavioral data. Analysis of behavioral sequential data often entails identifying
      patterns specified by the researchers. Algorithms were developed and applied to
      analyze a kind of behavioral data, called discrete action protocol data. Discrete
      action protocols consist of discrete user actions, such as mouse clicks and
      keypresses. Unfortunately, the process of analyzing the huge volume of actions
      (typically, > 10(5)) is very labor intensive. To facilitate this process, we
      developed an action protocol analyzer (ACT-PRO) that provides two levels of
      pattern matching. Level one uses formal grammars to identify sequential patterns.
      Level two matches these patterns to a hierarchical structure. ACT-PRO can be used
      to determine how well data fit the patterns specified by an experimenter.
      Complementarily, it can be used to focus an experimenter's attention on data that
      do not fit the prespecified patterns.

PMID- 11447668
TI  - VIDANN: a video annotation system.
AB  - VIDANN is a computer program that allows participants to watch a video on a
      standard TV and to write their annotations (thought/feeling entries) on paper
      attached to a writing tablet. The system is designed as a Microsoft ActiveX
      module. It can be further adapted by the individual researcher through the use of
      a VBScript. All data, including the participant's handwriting, are stored in an
      XML database. An accompanying Wizard has been designed that enables researchers
      to generate VBScripts for standard configurations.

PMID- 11447669
TI  - Real-time data collection in Linux: a case study.
AB  - Multiuser UNIX-like operating systems such as Linux are often considered
      unsuitable for real-time data collection because of the potential for
      indeterminate timing latencies resulting from preemptive scheduling. In this
      paper, Linux is shown to be fully adequate for precisely controlled programming
      with millisecond resolution or better. The Linux system calls that subserve such
      timing control are described and tested and then utilized in a MIDI-based program
      for tapping and music performance experiments. The timing of this program,
      including data input and output, is shown to be accurate at the millisecond
      level. This demonstrates that Linux, with proper programming, is suitable for
      real-time experiment software. In addition, the detailed description and test of
      both the operating system facilities and the application program itself may serve
      as a model for publicly documenting programming methods and software performance
      on other operating systems.

PMID- 11447670
TI  - Millisecond timing on PCs and Macs.
AB  - A real-time, object-oriented solution for displaying stimuli on Windows 95/98,
      MacOS and Linux platforms is presented. The program, written in C++, utilizes a
      special-purpose window class (GLWindow), OpenGL, and 32-bit graphics
      acceleration; it avoids display timing uncertainty by substituting the new window
      class for the default window code for each system. We report the outcome of tests
      for real-time capability across PC and Mac platforms running a variety of
      operating systems. The test program, which can be used as a shell for programming
      real-time experiments and testing specific processors, is available at
      http://www.cs.dal.ca/~macinnwj. We propose to provide researchers with a sense of
      the usefulness of our program, highlight the ability of many multitasking
      environments to achieve real time, as well as caution users about systems that
      may not achieve real time, even under optimal conditions.

PMID- 11447671
TI  - An inaccurate-timing filter for reaction time measurement by JAVA applets
      implementing Internet-based experiments.
AB  - JAVA applets are not accurate enough to measure reaction time unless precautions
      are taken. A response-filtering technique is introduced that identifies
      inaccurate measurements by testing whether the client-side JAVA implementation
      produces false measurements of a time interval of known length during the
      measured reaction time. Reaction times that indicate such inaccuracy are
      discarded to increase the reliability of the remaining data. Three studies
      provide illustrative data on the effectiveness of the new technique, using 11
      different computer systems. Study 1 showed differences in the accuracy of
      different clients and higher variability of the obtained means with applets than
      with native programs. Study 2 showed sharply increased variability when
      additional loads were imposed on the clients during reaction time measurement.
      The response-filtering technique diminishes this variability. Study 3 indicated
      more accurate measurement, with the new technique being able to reveal even
      smaller differences in difficult technical conditions.

PMID- 11447672
TI  - Presentation accuracy of Web animation methods.
AB  - Several Web animation methods were independently assessed on fast and slow
      systems running two popular Web browsers under MacOS and Windows. The methods
      assessed included those requiring programming (Authorware, Java,
      Javascript/Jscript), browser extensions (Flash and Authorware), or neither
      (animated GIF). The number of raster scans that an image in an animation was
      presented for was counted. This was used as an estimate of the minimum
      presentation time for the image when the software was set to update the animation
      as quickly as possible. In a second condition, the image was set to be displayed
      for 100 msec, and differences between observed and expected presentations were
      used to assess accuracy. In general, all the methods except Java deteriorated as
      a function of the speed of the computer system, with the poorest temporal
      resolutions and greatest variability occurring on slower systems. For some
      animation methods, poor performance was dependent on browser, operating system,
      system speed, or combinations of these.

PMID- 11447673
TI  - The Web Experimental Psychology Lab: five years of data collection on the
      Internet.
AB  - In fall 1995, the worldwide-accessible Web Experimental Psychology Lab
      (http://www.genpsylab.unizh.ch) opened its doors to Web surfers and Web
      experimenters. It offers a frequently visited place at which to conduct true
      experiments over the Internet. Data from 5 years of laboratory running time are
      presented, along with recommendations for setting up and maintaining a virtual
      laboratory, including sections on the history of the Web laboratory and of Web
      experimenting, the laboratory's structure and design, visitor demographics, the
      Kids' Experimental Psychology Lab, access statistics, administration, software
      and hardware, marketing, other Web laboratories, data security, and data quality.
      It is concluded that experimental data collection via the Internet has proven to
      be an enrichment to science. Consequently, the Web Experimental Psychology Lab
      will continue and extend its services to the scientific community.

PMID- 11447674
TI  - Mastery quizzes on the Web: results from a Web-based introductory psychology
      course.
AB  - Quizzes on the Web (QUEB) is a system for delivery of multiple-choice quizzes
      over the World Wide Web implemented as a set of Perl scripts. Items are contained
      in a text file and are randomly selected and ordered, and rich feedback is
      provided to the student. QUEB is in its fifth year of use as a mastery quiz
      system in an on-line psychology course. QUEB is highly rated by students, and its
      use is correlated with performance on examinations.

PMID- 11447675
TI  - Time as a variable in learning on the World-Wide Web.
AB  - Research in education, psychology, and neuroscience motivates a hypothesis that
      learning takes time. Support for the hypothesis was found in four replications of
      an upper level undergraduate course in which the material and activities for 50%
      of the topics were delivered over the World-Wide Web. Computer records were
      correlated with three types of test questions: multiple-choice, short-answer, and
      open-ended essay questions. Positive and significant correlations with time were
      observed for 33% of the correlations involving multiple-choice questions, 13% of
      those involving short-answer questions, and 60% of those involving open-ended
      essay questions. An estimate of the common underlying correlation, rho, equal to
      .35 for the four replications was significant. The data also revealed generally
      low overall study times and a maladaptive pattern of "cramming" before tests
      instead of distributing practice. In the Discussion section, we argue that
      computer study times can be used as a predictor of subsequent test performance,
      which is a measure of student learning.

PMID- 11447676
TI  - Methodological variables in Web-based research that may affect results: sample
      type, monetary incentives, and personal information.
AB  - There are many methodological differences between Web-based studies, differences
      that could substantially affect the results. The present study investigated
      whether sample type, offering payment through a lottery, and requiring
      participants to enter personal information would affect dropout rates and/or the
      substantive results in a study of jury decision making in capital cases. Asking
      participants to enter their e-mail addresses increased dropout rates, and
      offering payment through a lottery tended to do so as well. Participants offered
      payment tended to be less likely to give death sentences, and sample type
      moderated the influence of attitudes toward the death penalty on verdicts.

PMID- 11447677
TI  - P1198: software for tracing decision behavior in lending to small businesses.
AB  - This paper describes a process-tracing software program specially designed to
      capture decision behavior in lending to small businesses. The source code was
      written in Lotus Notes. The software runs in a Web browser and consists of two
      interacting systems: a database and a user interface. The database includes three
      realistic loan applications. The user interface consists of different but
      interacting screens that enable the participant to operate the software. Log
      files register the decision behavior of the participant. An empirical example is
      presented in order to show the software's potential in providing insights into
      judgment and decision making. The implications of the software are discussed.

PMID- 11447678
TI  - Visualizing individual differences in Web navigation: STRATDYN, a tool for
      analyzing navigation patterns.
AB  - Navigational behavior on the Web can be analyzed with different methods. Log file
      data are an important source of behavioral traces of navigation. In this paper,
      we first discuss existing approaches to the classification and visualization of
      movement sequences that are important for understanding Web navigation. We then
      present STRATDYN, a tool that provides meaningful quantitative and qualitative
      measures from server-generated log files, as well as easy-to-follow
      visualizations of navigational paths of individual users. We demonstrate the
      usefulness of this new approach by reporting the results of two studies (with 44
      students in education and vocational training), which show that navigational
      effectiveness is positively related to the ability to concentrate and selectively
      focus attention, as measured by the D2 Test of Attention and the FWIT, a German
      version of the Stroop test. Finally, we discuss implications for further research
      in this area and for the continuing development of the approach presented.

PMID- 11447679
TI  - A Web site in cognitive science.
AB  - A Web site (http://web2-pc.uncc.edu/cogsci) has been established to support an
      interdisciplinary course in cognitive science. The modules include introductory
      reading material, interactive exercises/virtual laboratory, and pointers to
      existing material on the Web. Our approach to using the Web in support of
      instruction differs from distance learning initiatives because it is centered on
      an instructor and classroom experiences. The Web-based modules are used to
      supplement classroom lectures and provide an interdisciplinary perspective.

PMID- 11447680
TI  - The Psychology Graduate Applicant's Portal (www.psychgrad.org).
AB  - Applying to graduate school in psychology can be an intimidating process. Many
      obstacles must be overcome, such as applying to a program appropriate to the
      specific applicant, getting good GRE scores, submitting a clear and well-written
      statement of purpose, and obtaining letters of recommendation, to name just a
      few. Much information is available to assist applicants in these tasks, but
      finding this information can cause problems even for experienced Internet users.
      The goal of this project is to create an easily accessible Web clearing house of
      information on applying to graduate school in psychology. This Web site, called
      the Psychology Graduate Applicant's Portal (or PsychGrad.org), contains targeted
      links to other Web pages with valuable information, book recommendations on the
      applications process, polls to measure issues important to the graduate
      applicants, site-unique advice on graduate programs, a message board to exchange
      information and experiences, and other information relevant to the application
      process.

PMID- 11447681
TI  - Audiovisual Speech Web-Lab: an Internet teaching and research laboratory.
AB  - Internet resources now enable laboratories to make full-length experiments
      available on line. A handful of existing web sites offer users the ability to
      participate in experiments and generate usable data. We have integrated this
      technology into a web site that also provides full discussion of the theoretical
      and methodological aspects of the experiments using text and simple interactive
      demonstrations. The content of the web site
      (http://www.psych.ucr.edu/avspeech/lab) concerns audiovisual speech perception
      and its relation to face perception. The site is designed to be useful for users
      of multiple interests and levels of expertise.

PMID- 11447682
TI  - Difference to Inference: teaching logical and statistical reasoning through on
      line interactivity.
AB  - Difference to Inference is an on-line JAVA program that simulates theory testing
      and falsification through research design and data collection in a game format.
      The program, based on cognitive and epistemological principles, is designed to
      support learning of the thinking skills underlying deductive and inductive logic
      and statistical reasoning. Difference to Inference has database connectivity so
      that game scores can be counted as part of course grades.

PMID- 11447683
TI  - MERLOT: a faculty-focused Web site of educational resources.
AB  - The Multimedia Educational Resource for Learning and Online Teaching (MERLOT) is
      a community of academic institutions, professional discipline organizations, and
      individual people building a collection of Web-based teaching and learning
      resources where faculty can easily find peer-reviewed materials for use in their
      classes. The MERLOT project is currently supported by 23 systems and institutions
      of higher education and by the National Science Foundation. MERLOT is developing
      collections of learning materials from many academic disciplines, including
      psychology.

PMID- 11447684
TI  - cTRAIN: a computer-aided training system developed in SuperCard for teaching
      skills using behavioral education principles.
AB  - A computer-aided training program was developed in SuperCard and piloted with
      professional painters. Taking a modern programmed-instruction/behavioral
      education approach, cTRAIN is structured as a series of information sets. Each
      information set consists of a series of information screens (three to five
      recommended) followed by quiz screens (one to three recommended) structured as
      four-response multiple choice questions. Correct quiz responses produce positive
      feedback and continuation in the series, whereas incorrect responses result in
      "error" feedback and return the student to the beginning of the information set
      to repeat the same information screens and the same quiz question. This report
      demonstrates a specific implementation, respiratory protection requirements,
      using the flexible cTRAIN system for developing training modules. Fifteen adults
      completed the respiratory protection program, demonstrating substantial and
      significant (p < .0001 by paired t test) gains from baseline pretest (19.4 out of
      30 questions) to the immediate posttest (28.1). Performance remained elevated
      (26.4) on a retest taken 1 week later.

PMID- 11447685
TI  - Utah Virtual Lab: JAVA interactivity for teaching science and statistics on line.
AB  - The Utah on-line Virtual Lab is a JAVA program run dynamically off a database. It
      is embedded in StatCenter (www.psych.utah.edu/learn/statsampler.html), an on-line
      collection of tools and text for teaching and learning statistics. Instructors
      author a statistical virtual reality that simulates theories and data in a
      specific research focus area by defining independent, predictor, and dependent
      variables and the relations among them. Students work in an on-line virtual
      environment to discover the principles of this simulated reality: They go to a
      library, read theoretical overviews and scientific puzzles, and then go to a lab,
      design a study, collect and analyze data, and write a report. Each student's
      design and data analysis decisions are computer-graded and recorded in a
      database; the written research report can be read by the instructor or by other
      students in peer groups simulating scientific conventions.

PMID- 11447686
TI  - Why we need more psychology programmers/EL Knife, a data utility for transforming
      spreadsheets.
AB  - The software needs of psychology researchers are sufficiently diverse that they
      cannot be met by the commercial sector. The field needs more psychologists who
      publish software, and individual researchers need to be able to write their own.
      To support this view, the author offers EL Knife, a data utility for
      reconfiguring multifactor spreadsheet files. Data may be divided by up to four
      factors, each of which may have an unlimited number of levels. The interface
      makes it easy to specify a wide variety of different configurations (different
      ways of packing multiple data dimensions into a two-dimensional spreadsheet).
      Many other possibilities for useful research software remain to be invented.

PMID- 11447687
TI  - Prion protein diversity and disease in the transmissible spongiform
      encephalopathies.

PMID- 11447688
TI  - Simulations and computational analyses of prion protein conformations.

PMID- 11447689
TI  - Interactions and conversions of prion protein isoforms.

PMID- 11447690
TI  - Studies on peptide fragments of prion proteins.

PMID- 11447691
TI  - Biosynthesis and cellular processing of the prion protein.

PMID- 11447692
TI  - Interaction of prion proteins with cell surface receptors, molecular chaperones,
      and other molecules.

PMID- 11447693
TI  - Transgenic studies of the influence of the PrP structure on TSE diseases.

PMID- 11447694
TI  - Mass spectrometric analysis of prion proteins.

PMID- 11447695
TI  - Yeast prions act as genes composed of self-propagating protein amyloids.

PMID- 11447696
TI  - [PSI+], SUP35, and chaperones.
AB  - Biochemical characterization of the yeast prions has revealed many similarities
      with the mammalian amyloidogenic proteins. The ease of generating in vivo
      mutations in yeast and the developing in vitro models for [PSI+] and [URE3]
      circumvent many of the difficulties of studying the proteins linked to the
      mammalian amyloidoses. Future work especially aimed at understanding the
      molecular role of chaperone proteins in regulating conversion as well as the
      early steps in de novo formation of the prion state in yeast will likely provide
      invaluable lessons that may be more broadly applicable to related processes in
      higher eukaryotes. It is important to remember, however, that there are clear
      distinctions between disease states associated with amyloidogenesis and the
      epigenetic modulation of protein function by self-perpetuating conformational
      conversions. Amyloid formation is detrimental to mammals and is likely selected
      against, providing a possible explanation for the late onset of these disorders
      (Lansbury, 1999). In contrast, the known yeast prions are compatible with normal
      growth and, if beneficial to the organism, may be subject to evolutionary
      pressures that ultimately maximize transmission. In the prion proteins examined
      to date, distinct domains are responsible for normal function and for the
      conformational switches producing a prion conversion of that function. Recent
      work has demonstrated that the prion domains are both modular and transferable to
      other proteins on which they can confer a heritable epigenetic alteration of
      function (Edskes et al., 1999; Li and Lindquist, 2000; Patino et al., 1996;
      Santoso et al., 2000; Sondheimer and Lindquist, 2000). That is, prion domains
      need not coevolve with particular functional domains but might be moved from one
      protein to another during evolution. Such processes may be widely used in
      biology. Mechanistic studies of [PSI+] and [URE3] replication are sure to lay a
      foundation of knowledge for understanding a host of nonconventional genetic
      elements that currently remain elusive.

PMID- 11447697
TI  - Three-dimensional structures of prion proteins.

PMID- 11447698
TI  - Folding dynamics and energetics of recombinant prion proteins.

PMID- 11447699
TI  - Infections in systemic lupus erythematosus and rheumatoid arthritis.
AB  - Patients with systemic lupus erythematosus have a higher infection rate than the
      general population. It is estimated that at least 50% of them will suffer a
      severe infectious episode during the course of the disease. Improvements in the
      control of the disease are discussed in this article.

PMID- 11447700
TI  - Infections in cirrhosis.
AB  - Infection is a well-described complication of cirrhosis and is a major cause of
      death in this population. This article examines the types of infections related
      with cirrhosis, such as bacteremia, urinary tract infections, meningitis, and
      others.

PMID- 11447701
TI  - Infections in multiple myeloma.
AB  - Multiple myeloma is a relatively rare but severe hematologic malignancy. Marked
      depression in production of normal immunoglobulins, mild neutropenia, and
      alkylant/steroid therapy or BMT/SCT all produce major suppression of the immune
      system in the totality of patients. Recurrent bacterial, fungal, and viral
      infections are an important cause of morbidity and the most common cause of death
      in these subjects. Prompt diagnosis and appropriate anti-infective chemotherapy
      are essential in order to reduce the risk of mortality.

PMID- 11447702
TI  - Infections associated with uremia and dialysis.
AB  - Patients with chronic renal failure are predisposed to infections. Infections in
      end-stage renal disease patients are caused by immunosuppressive effects of
      uremia. Patients with renal failure on dialysis have impaired host defenses and
      may develop infections related to vascular access. This article reviews the
      infectious complications related to chronic renal failure in dialysis.

PMID- 11447703
TI  - Infections in diabetes.
AB  - Diabetics are predisposed to infections because of various immune deficiencies,
      including neutrophil and monocyte dysfunction. Some of these immune deficiencies
      are improved by tight glucose control. This article is a review of the immune
      deficiencies seen in diabetes and an overview of selected infections that are
      commonly or predominantly seen in diabetics.

PMID- 11447704
TI  - Infections associated with steroid use.
AB  - Patients receiving chronic steroids have an increased susceptibility to many
      different types of infections. The risk of infection is related to the dose of
      steroid and the duration of therapy. Although pyogenic bacteria are the most
      common pathogens, chronic steroid use increases the risk of infection with
      intracellular pathogens such as Listeria, many fungi, the herpes viruses, and
      certain parasites. Clinicians should consider both common and unusual
      opportunistic infections in patients receiving chronic steroids.

PMID- 11447705
TI  - Opportunistic infections in HIV disease: down but not out.
AB  - Despite the marked improvement in patient survival and reduction in the incidence
      of HIV-related opportunistic infections with the introduction of potent,
      combination antiretroviral therapy, these infections remain a significant
      challenge in the management of HIV-infected patients. Ongoing issues that will
      require further study include a better characterization of immune reconstitution
      illnesses, other potential alterations in the natural history of opportunistic
      infections with antiretroviral therapy, and to what degree patients who
      experience failure of antiviral treatment become susceptible to various
      opportunistic processes.

PMID- 11447706
TI  - Infectious complications of febrile leukopenia.
AB  - It can be foreseen that in the years to come major improvements in neutropenic
      host infections will be achieved regarding the exact identification of risk
      factors, allowing better patient stratification; the application of molecular
      techniques to recognize pathogens; the development of effective new oral
      antimicrobials allowing home therapy or abbreviated hospitalization; the
      development of new antifungals; and the development of new effective
      immunomodulators and cytokines to ameliorate chemotherapy-induced neutropenia. In
      the years to come the threat of nosocomial infections unfortunately will not be
      eliminated, while the development of major new parenteral antibiotics cannot be
      foreseen. It is therefore the caregiver/physician himself who, by applying
      rational antibiotic policies and strict handwashing rules, will probably escape,
      for his neutropenic patient's sake, the imminent threat of multiresistant
      pathogens.

PMID- 11447707
TI  - Infections following hematopoietic stem cell transplantation.
AB  - Numerous advances have been made in the management of infection in HSCT
      recipients. With increasing knowledge the authors are able to prevent several
      serious infections from occurring, and reduce the severity of infections once
      they occur. Despite these advances, several previously unrecognized pathogens
      have emerged and pose risks to this population. Ongoing surveillance and
      reporting of atypical infections are warranted. Transplant and infectious disease
      clinicians alike must be vigilant to the shifts in infectious syndromes as a
      consequence of various prophylaxis and preemptive strategies, and be ready to
      modify empiric strategies to meet the changing microbiologic milieu. As we
      increase our understanding of the HSCT process, and use the immune system rather
      than relying on high-dose chemotherapy, the authors are likely to reduce
      toxicities and improve patient outcomes.

PMID- 11447708
TI  - Infectious complications of solid organ transplantations.
AB  - The rate of infectious complications in SOT recipients has declined dramatically.
      As improvements in immunosuppressive therapy, surgical techniques, and
      diagnostics and antimicrobial treatment continue, further declines in infectious
      complications are expected. Refinements to preemptive therapy for high-risk
      patients are likely to contribute further to this decrease. Further investigation
      is required to define what role various infectious agents play in chronic
      allograft injury and rejection.

PMID- 11447709
TI  - Infectious complications in asplenic hosts.
AB  - Hyposplenism, secondary to splenectomy or disease state, predisposes the host to
      overwhelming infection with certain bacteria, such as S. pneumoniae. Recognition
      of the hyposplenic state and preventive measures, including patient education and
      vaccination, appear to reduce the rate of this highly fatal infection. In
      addition to considering chemoprophylaxis, a clinician should promptly evaluate or
      empirically treat all febrile episodes in hyposplenic patients.

PMID- 11447710
TI  - Central nervous system infections in the compromised host: a diagnostic approach.
AB  - The diagnostic approach to the compromised host with CNS infection depends on an
      analysis of the patient's clinical manifestations of CNS disease, the acuteness
      or subacuteness of the clinical presentation, and an analysis of the type of
      immune defect compromising the patient's host defenses. Most patients with CNS
      infections may be grouped into those with meningeal signs, or those with mass
      lesions. Other common manifestations of CNS infection include encephalopathy,
      seizures, or a stroke-like presentation. Most pathogens have a predictable
      clinical presentation that differs from that of the normal host. CNS Aspergillus
      infections present either as mass lesions (e.g., brain abscess), or as cerebral
      infarcts, but rarely as meningitis. Cryptococcus neoformans, in contrast, usually
      presents as a meningitis but not as a cerebral mass lesion even when cryptococcal
      elements are present. Aspergillus and Cryptococcus CNS infections are
      manifestations of impaired host defenses, and rarely occur in immunocompetent
      hosts. In contrast, the clinical presentation of Nocardia infections in the CNS
      is the same in normal and compromised hosts, although more frequent in
      compromised hosts. The acuteness of the clinical presentation coupled with the
      CNS symptomatology further adds to limit differential diagnostic possibilities.
      Excluding stroke-like presentations, CNS mass lesions tend to present subacutely
      or chronically. Meningitis and encephalitis tend to present more acutely, which
      is of some assistance in limiting differential diagnostic possibilities. The
      analysis of the type of immune defect predicts the range of possible pathogens
      likely to be responsible for the patient's CNS signs and symptoms. Patients with
      diseases and disorders that decrease B-lymphocyte function are particularly
      susceptible to meningitis caused by encapsulated bacterial pathogens. The
      presentation of bacterial meningitis is essentially the same in normal and
      compromised hosts with impaired B-lymphocyte immunity. Compromised hosts with
      impaired T-lymphocyte or macrophage function are prone to develop CNS infections
      caused by intracellular pathogens. The most common intracellular pathogens are
      the fungi, particularly Aspergillus, other bacteria (e.g., Nocardia), viruses
      (i.e., HSV, JC, CMV, HHV-6), and parasites (e.g., T. gondii). The clinical
      syndromic approach is most accurate when combining the rapidity of clinical
      presentation and the expression of CNS infection with the defect in host
      defenses. The presence of extra-CNS sites of involvement also may be helpful in
      the diagnosis. A patient with impaired cellular immunity with mass lesions in the
      lungs and brain that have appeared subacutely or chronically should suggest
      Nocardia or Aspergillus rather than cryptococcosis or toxoplasmosis. Patients
      with T-lymphocyte defects presenting with meningitis generally have meningitis
      caused by Listeria or Cryptococcus rather than toxoplasmosis or CMV infection.
      The disorders that impair host defenses, and the therapeutic modalities used to
      treat these disorders, may have CNS manifestations that mimic infections of the
      CNS clinically. Clinicians must be ever vigilant to rule out the mimics of CNS
      infections caused by noninfectious etiologies. Although the syndromic approach is
      useful in limiting diagnostic possibilities, a specific diagnosis still is
      essential in compromised hosts in order to describe effective therapy. Bacterial
      meningitis, cryptococcal meningitis, and tuberculosis easily are diagnosed
      accurately from stain, culture, or serology of the CSF. In contrast, patients
      with CNS mass lesions usually require a tissue biopsy to arrive at a specific
      etiologic diagnosis. In a compromised host with impaired cellular immunity in
      which the differential diagnosis of a CNS mass lesion is between TB, lymphoma,
      and toxoplasmosis, a trial of empiric therapy is warranted. Antitoxoplasmosis
      therapy may be initiated empirically and usually results in clinical improvement
      after 2 to 3 weeks of therapy. The nonresponse to antitoxoplasmosis therapy in
      such a patient would warrant an empiric trial of antituberculous therapy. Lack of
      response to anti-Toxoplasma and antituberculous therapy should suggest a
      noninfectious etiology (e.g., CNS lymphoma). Fortunately, most infections in
      compromised hosts are similar in their clinical presentation to those in the
      normal host, particularly in the case of meningitis. The compromised host is
      different than the normal host in the distribution of pathogens, which is
      determined by the nature of the host defense defect. In compromised hosts,
      differential diagnostic possibilities are more extensive and the likelihood of
      noninfectious explanations for CNS symptomatology is greater. (ABSTRACT
      TRUNCATED)

PMID- 11447711
TI  - Pneumonias in the compromised host.
AB  - The choice of diagnostic modality depends on the patient's status, the expertise
      of the operator and pathologic resources of the hospital, and is a decision that
      should be guided by the infectious disease consultant and the clinicians involved
      in the care of the patient. Although the diagnosis must be tissue based, every
      attempt must be made to arrive at a tissue diagnosis as soon as possible in order
      to start specific therapy as soon as possible. It is as important to determine
      that the cause of the patient's pulmonary infiltrate is noninfectious versus
      infectious. Pulmonary embolic disease, CHF, ARDS, pulmonary hemorrhage, and
      pulmonary drug reactions may be reversible and require nonantimicrobially based
      therapies to treat the patient. Often clinicians are overwhelmed by differential
      diagnostic possibilities of exotic infectious disease pathogens and overlook
      easily treatable noninfectious disease mimics of pneumonia. Although differential
      diagnostic possibilities are great in the compromised host, clinicians should not
      be overwhelmed by diagnostic possibilities. Instead, clinicians should try to
      approach the patient syndromically, taking into account the degree and type of
      immunosuppression, the appearance and behavior of the infiltrates on the chest
      radiograph and the nature of the host defense defects and time relationships that
      will limit the differential diagnosis to relatively few diagnostic possibilities.
      The clinician can then treat empirically patients with presumed bacterial
      pneumonias and devise a diagnostic plan designed to arrive at a specific tissue
      diagnosis as soon as possible in patients who are likely to have nonbacterial
      infection of the lungs.

PMID- 11447712
TI  - Cardiac infections in the immunosuppressed patient.
AB  - This article presents the various manifestations of cardiac infections found in
      the immunosuppressed host. Emphasis is placed on the correlation between specific
      impairments of host defenses and the occurrence of certain types of pathogens.
      The effect of immunosuppression on the clinical manifestations of these
      infections is discussed. Finally, appropriate diagnostic modalities are presented
      for the major types of infections.

PMID- 11447713
TI  - Gastrointestinal infections in the immunocompromised host.
AB  - Gastrointestinal disease is a significant cause of morbidity and mortality in the
      immunocompromised patient. This article focuses on the infectious
      gastrointestinal complications associated with the treatment of malignant disease
      and with solid organ transplantation but not HIV. Gastrointestinal defenses and
      the various mechanisms by which they are impaired are reviewed. The major
      pathogens and malignancies of this patient population and an approach to their
      diagnosis, treatment, and prevention are discussed.

PMID- 11447714
TI  - Dermatologic infections in the immunocompromised (non-HIV) host.
AB  - The immunocompromised host's susceptibility to infections often present a
      difficult diagnostic challenge to the physician. A working knowledge of the host
      immune defenses and microbiologic complications that can occur when these
      functions are compromised provides a more focused framework for further
      evaluation and management. Infections in these patients are often morbid and life
      threatening, creating an urgent need for prompt diagnosis. The skin may manifest
      the first clue(s) of a serious underlying infection. Appropriate workup and
      diagnosis of cutaneous lesions provide an expeditious, noninvasive, and
      potentially life-saving approach to the immunocompromised host with a
      dermatologic infection.

PMID- 11447715
TI  - Treatability under psychiatrist: personal, ethical and resource constraints.

PMID- 11447716
TI  - Medical negligence--is there something wrong?

PMID- 11447717
TI  - E coli and food safety.

PMID- 11447718
TI  - Drug induced injury and informed consent.

PMID- 11447719
TI  - [Treatment of Parkinson patients].

PMID- 11447720
TI  - [Therapy of idiopathic Parkinson syndrome 1817 to 2001. A success story?].
AB  - It lasted some 150 years after the first description by James Parkinson in 1817
      until levodopa, the first really efficacious treatment, was available for
      Parkinson's disease. Previously only anticholinergic substances and stereotaxic
      operations, both acting merely exclusively on tremor, were used for many and a
      few years respectively. Even today the treatment is purely symptomatic. There is
      no treatment in sight which would cure the disease or at least stop or slow down
      its progression.

PMID- 11447721
TI  - [The genetics of Parkinson syndrome].
AB  - A genetic contribution to the etiology of Parkinson's disease was first suspected
      by Charcot and later confirmed by case control, family, and twin studies, as well
      as by the description of large parkinsonian families with Mendelian inheritance
      of the disease. Recent progress in the field of molecular neurogenetics has led
      to the identification of several Parkinson disease genes and gene loci. Mutations
      in the alpha-Synuclein gene (PARK1) and in the gene for the ubiquitin C-terminal
      hydrolase I (PARK5), along with two gene loci harboring currently unknown genes
      (PARK3 and PARK4), have been linked to very rare autosomal dominantly inherited
      parkinsonian syndromes. Mutations in the parkins gene (PARK2), causing autosomal
      recessive early-onset parkinsonism, are much more common and therefore of
      clinical relevance. A second gene locus for an autosomal dominantly inherited
      Parkinsonian syndrome was recently localized on chromosome 1 (PARK6). All three
      parkinson genes identified thus far imply the involvement of the ubiquitin
      pathway of protein degradation in the pathogenesis of Parkinson's disease.

PMID- 11447722
TI  - [Parkinson therapy 2001, especially apomorphine in idiopathic Parkinson
      syndrome].
AB  - Today (2001) most strategies for Parkinson's disease (PD) are symptomatic. The
      etiology of the disease is not known. There exists no possibility to inhibit the
      degeneration of dopaminergic neurons in the substantia nigra. There are hints
      (but no proofs) for neuroprotection. Beside levodopa a variety of alternative
      treatment options exists which enable a good and longer lasting control of
      symptoms (e.g. dopamine agonists, COMT-inhibitors etc.). Apomorphine can reduce
      off-periods and fluctuations remarkably, even in more advanced stages of PD. Some
      patients may take profit from neurosurgical procedures (especially deep brain
      stimulation of subthalamic nucleus and globus pallidus internus).
      Rehabilitative/supportive approaches complete the medical regime, but there is no
      proof of efficacy.

PMID- 11447723
TI  - [Diagnosis and therapy of multiple system atrophy].
AB  - Numerous studies of the past years have established the clinical features, course
      and neuropathology characterizing multiple system atrophy (MSA). Clinically, two
      motor subtypes can be classified based on the predominance of a parkinsonian
      syndrome refractory to L-dopa and cerebellar ataxia. 80% of the cases involve MSA
      P (the parkinsonian variant of MSA) and 20% MSA-C (cerebellar variant of MSA).
      Virtually all of these patients show disturbances of autonomic and urogenital
      function, half of the patients also exhibit pyramidal signs. Neuropathologically,
      MSA-C is based on an olivopontocerebellar atrophy (OPCA) and MSA-P on
      striatonigral degeneration (SND). However, a combination of OPCA and SND
      pathologies is observed in most cases. Recent evidence suggests that a key
      pathogenetic role may be played by glial alpha synuclein-containing inclusion
      bodies, which might lead to neuronal dysfunction and ultimately to cell loss.
      There is no therapy known to be effective in treating the motor disorders of MSA
      C. By contrast, L-dopa replacement is at least transiently effective in about 30%
      of patients with MSA-P. Currently, initial efforts are being undertaken
      throughout Europe to develop neuroprotective solutions. Experiments are underway
      to test whether neurotransplantation by striatal grafting is a suitable method
      for inducing a clinically relevant response to L-dopa. Neurologically, the
      options for treating orthostatic hypertension and urogenital disorders are often
      overlooked.

PMID- 11447724
TI  - [Parkinson disease].

PMID- 11447725
TI  - [Pressure-induced acute tetraplegia. Tetraplegia of uncertain origin].

PMID- 11447726
TI  - Pubertal disorders in inv dup(15) syndrome.
AB  - Duplication of chromosome 15 (inv dup[15] chromosome) is the most common
      supernumerary marker chromosome in humans. Inv dup(15) chromosomes are commonly
      associated with mental retardation, epilepsy, behavioral problems and structural
      malformations. Ten patients (4 male, 6 female) were detected with inv dup(15)
      syndrome. At clinical follow-up three girls showed pubertal disorders: two with
      central precocious puberty and one with ovarian dysgenesis. As has already been
      found in other patients with chromosome 15p abnormalities, we believe that
      gynecological disorder is an important clinical finding also in patients with inv
      dup(15) syndrome. We report the first data of a systematic endocrinological study
      on inv dup(15) syndrome which suggest that endocrine investigation in these
      patients is both warranted and useful. Moreover, our observations confirm that a
      karyotype analysis in patients in whom precocious puberty is associated with
      mental retardation is mandatory.

PMID- 11447727
TI  - Menstrual irregularity in the first postmenarchal years: an early clinical sign
      of polycystic ovary syndrome in adolescence.
AB  - We determined the hormonal, metabolic and ultrasonographic pattern of adolescents
      with menstrual irregularity since menarche but without clinical signs of
      hyperandrogenism with the aim of evaluating whether this condition represents an
      early stage of polycystic ovary syndrome (PCOS). These adolescents were divided
      in two groups: 13 adolescents with irregular cycles (IC) within the first 3
      postmenarchal years (IC < or = 3) and 15 adolescents having persistent irregular
      cycles for more than three postmenarchal years (IC > 3). These adolescents were
      compared with 15 adolescents with PCOS and 18 normal adolescents. The values of
      free testosterone, free androgen index, luteinizing hormone (LH) and LH/follicle
      stimulating hormone (FSH) ratio were similar in IC < or = 3, IC > 3 and PCOS, and
      higher than in the normal group (p < 0.005). The total testosterone and
      androstenedione levels were higher and sex hormone-binding globulin (SHBG) lower
      in PCOS only when compared with the normal group (p < 0.05). The ovarian volume
      was similar in IC < or = 3, IC > 3 and PCOS, and higher than in the normal group
      (p < 0.005). A higher incidence of polycystic structure was found in IC < or = 3,
      IC > 3 and PCOS, whereas normal structure was more common in normal adolescents
      (p < 0.0005). There were no significant differences in glucose and insulin
      parameters between groups. These results indicate that menstrual irregularity
      within the first postmenarchal years can be an early clinical sign of PCOS.

PMID- 11447728
TI  - Neuroendocrine features of pubertal development in females with mental
      retardation.
AB  - In order to evaluate the hypothalamic-pituitary effects of mental retardation
      during pubertal development, follicle-stimulating hormone (FSH) and luteinizing
      hormone (LH) responses to gonadotropin-releasing hormone (GnRH) administration
      were evaluated at various pubertal stages in a female population with mental
      retardation (MR) compared to a healthy control group of adolescents. Fifty-six
      girls aged 8-16 years with MR and 146 normal females of the same age participated
      in the study. The analyzed subjects were divided into different pubertal stages,
      ranging from P2 to P5, in line with their degree of sexual maturation. Each
      patient underwent a GnRH test (100 micrograms); blood samples were collected
      basally and 15, 30, 60, 90 minutes after the GnRH injection. FSH and LH were
      assayed in each sample; the gonadotropin response to GnRH administration was
      evaluated as incremental area. No differences were found at any pubertal stage
      between the two studied groups with regard to the age, body mass index, or age at
      menarche. Patients with mental retardation during stages P2 and P3 showed lower
      FSH secretion in response to GnRH bolus compared with control subjects (P2, p <
      0.05; P3, p < 0.01). In conclusion, our data show that MR is related to an
      impaired response of the FSH-secreting pituitary cells to their appropriate
      stimulus; this feature is present only in the initial pubertal stages, whereas it
      disappears during sexual development.

PMID- 11447729
TI  - Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on progestin
      biosynthesis in cultured luteal cells from rat ovary.
AB  - We examined the effects of pituitary adenylate cyclase-activating polypeptide
      (PACAP) on progestin biosynthesis in cultured luteal cells from rat ovary. Luteal
      cells from immature rats treated with pregnant mare serum gonadotropin (PMSG) and
      human chorionic gonadotropin (hCG) were cultured in the absence or presence of
      ovine luteinizing hormone (LH) (100 ng/ml) and PACAP-38 (10, 100 and 1000 ng/ml).
      Following 48 hours of incubation, the levels of progesterone, 20 alpha-hydroxy-4
      pregnene-3-one (20 alpha-OH-P) and adenosine 3',5'-monophosphate (cAMP) were
      measured in the culture media. PACAP alone significantly stimulated the
      production of progesterone and 20 alpha-OH-P in a dose-dependent manner (p < 0.01
      and 0.05, respectively, ANOVA). LH-induced production of progesterone and
      accumulation of cAMP were significantly decreased by increasing concentrations of
      PACAP (p < 0.05 for each, ANOVA). Conversely, LH-stimulated 20 alpha-OH-P
      production was enhanced by PACAP in a dose-dependent manner (p < 0.05). Since
      PACAP decreased the ratio of progesterone to 20 alpha-OH-P production in LH
      stimulated cells, PACAP-mediated inhibition of the stimulatory action of LH on
      progesterone production may be involved in the initiation of luteolysis. PACAP-38
      also suppressed increases in LH receptor content in cultured luteal cells. These
      results suggest that PACAP regulates the effects of LH on luteal cell function
      and that PACAP might be closely linked to reproduction.

PMID- 11447730
TI  - Simplification of continuous infusion of glucose with model assessment in the
      evaluation of insulin resistance in women with PCOS.
AB  - Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin
      resistance and glucose tolerance by means of the continuous infusion of glucose
      with model assessment (CIGMA) test. The mean concentrations of glucose and
      insulin at 50, 55 and 60 min of glucose infusion were interpreted using a
      mathematical model of glucose and insulin homeostasis, and an insulin resistance
      index (IR1) was obtained. Using insulin and glucose values at 60 min only, a new
      insulin resistance index (IR2) was obtained using the same mathematical method.
      In addition, fasting insulin, fasting C-peptide, fasting glucose, fasting
      insulin:glucose ratio and fasting C-peptide:glucose ratio were also used to
      assess insulin resistance. There were significant correlations between IR1 and
      IR2, fasting glucose, fasting insulin, fasting insulin:glucose ratio, fasting C
      peptide:glucose ratio. IR2 had the highest correlation with IR1 (r = 0.97, p <
      0.001) and provided the best combination of sensitivity (82.9%), specificity
      (93.9%), positive predictive value (91.9%) and negative predictive value (86.8%).
      In conclusion, the simplified CIGMA test, using insulin and glucose concentration
      at 60 min of glucose infusion only, is a highly sensitive and specific measure of
      insulin sensitivity in women with PCOS.

PMID- 11447731
TI  - Divalent cations in women with PCOS: implications for cardiovascular disease.
AB  - Polycystic ovary syndrome (PCOS) patients are known to have a high incidence of
      insulin resistance and glucose intolerance and tend to be at eventual high risk
      of hypertension, diabetes mellitus and cardiovascular disease. It has been
      repeatedly shown that a low serum ionized magnesium (Mg2+) and a high ionized
      calcium to magnesium (Ca2+/Mg2+) ratio is often associated with insulin
      resistance, cardiovascular problems, diabetes mellitus and hypertension. We were
      therefore interested in assessing the serum divalent cation profile of PCOS
      patients compared with that of normal women of similar age. We found
      significantly lower serum Mg2+ and total magnesium and a significantly higher
      serum Ca2+/Mg2+ ratio in the PCOS patients compared with the controls. No
      correlation was found, however, between the serum concentrations of steroid
      hormones (estrogen, progesterone and testosterone), or any of the cations in the
      PCOS patients or the controls.

PMID- 11447732
TI  - Prospective randomized study comparing the GnRH-agonist leuprorelin acetate and
      the gestagen lynestrenol in the treatment of severe endometriosis.
AB  - Endometriosis is thought to be an ovarian-dependent benign disease that affects
      up to 12% of women during their reproductive life. For the past ten years the
      gonadotropin-releasing hormone (GnRH)-agonists have been proved effective and
      safe drugs in the treatment of endometriosis. Nevertheless, gestagens such as
      lynestrenol still remain the most often used hormonal drugs for the treatment of
      this disease. The primary objective of this study was to compare the efficacy of
      the GnRH-agonist leuprorelin acetate depot (LAD) (Enantone-Gyn) 3.75 mg
      subcutaneously per month with that of the gestagen lynestrenol (LYN) (Orgametril)
      5 mg orally twice per day in women with severe endometriosis, in terms of
      postoperative revised American Fertility Society (r-AFS) scores I-IV at first
      look laparoscopy (score after removal of endometriotic lesions or adhesions) to
      the r-AFS score after six months' treatment. Secondary objectives were the
      improvement of clinical symptoms and the side-effect profile. Forty-eight women
      with postoperative r-AFS scores I-IV were evaluated in an open prospective
      randomized study between 1996 and 1998. All the participants underwent a first
      look laparoscopy with resection of endometriotic lesions and six months' therapy
      with one of the above mentioned drugs, and a further second-look laparoscopy. The
      six months' treatment with LAD or LYN led to a significant reduction of the r-AFS
      score points in both groups. The mean r-AFS score in points for the LAD group
      after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group. After
      the medical treatment a mean value of 11.5 points was observed in the LAD group
      compared with a mean value of 25.5 in the LYN group. This difference was
      statistically significant (p = 0.000014, Wilcoxon test). The improvement in the
      symptoms of dysmenorrhea, chronic pelvic pain and dyspareunia was also more
      pronounced in the LAD-treated group. LAD was more effective than LYN in the
      suppression of circulating serum 17 beta-estradiol levels after 6 months of
      treatment (mean 27.7 +/- 9.3 pg/ml versus 42.6 +/- 59.3 pg/ml). All the observed
      side-effects were deemed tolerable by the women who participated in this study.
      As the reduction of the r-AFS score in points was much more pronounced in the LAD
      group than in the LYN group, GnRH-agonists should therefore be used as first
      choice drugs in the treatment of endometriosis. Due to the limited treatment of 6
      months' duration of GnRH-agonists, gestagens might be used as second-line drugs
      for long-term and continuous treatment in the management of endometriosis to
      maintain the primary beneficial effect of GnRH-agonist treatment in patients who
      have completed their families.

PMID- 11447733
TI  - Determination of endometrial prolactin in vivo as a marker for endometrial
      development in spontaneous ovulatory cycles and in vitro fertilization cycles.
AB  - Decidual prolactin was directly determined in endometrial tissue in order to
      assess its potential role in improving the accuracy of the diagnosis of luteal
      phase defect (LPD). Endometrial biopsies of 124 women with regular cycles (group
      1) and 13 women with controlled ovarian hyperstimulation and progesterone
      supported cycles (group 2) were evaluated in the secretory phase. In addition,
      decidual prolactin was measured in the luteal phase of the in vitro fertilization
      (IVF) cycles. The biopsies dated on or after day 25 showed a significant increase
      in the slope of the regression line of the cycle day versus decidual prolactin
      content (p < 0.05). Delayed endometrium was not characterized by a lower amount
      of decidual prolactin compared with biopsies with the same histological dating.
      On day 27 of the cycle, less prolactin was measured in the out-of-phase biopsies
      (p < 0.05). A large inter-individual variation in endometrial prolactin tissue
      content was noticed. In group 2 all biopsies but one were in phase. Compared to
      the in-phase biopsies of group 1, a significantly higher amount of prolactin was
      found in group 2. Production of endometrial prolactin in vivo is associated with
      decidualization of the stromal cells. However, because of the large inter
      individual variation, determination of prolactin is not of adjuvant diagnostic
      value for clinical assessment of LPD. Three factors might explain the higher
      amount of decidual prolactin in group 2 compared to group 1: (1) a higher serum
      progesterone concentration owing to an increased production by multiple corpora
      lutea, or because of the administered progesterone; (2) increased estradiol
      levels and thus progesterone receptors; and (3) direct stimulation of
      decidualization by gonadotropins.

PMID- 11447734
TI  - Expression of glucose transporter 1 in human endometrial and decidual tissue.
AB  - Regulation of endometrial glucose transport is important for the decidualization
      process. Therefore, we have examined the expression of the glucose transporter
      protein isoform 1 (GLUT1) in endometrial samples during the menstrual cycle and
      in decidual tissue by immunohistochemistry, and GLUT1 mRNA by RNase protection
      assays. GLUT1 protein was not detected in proliferative endometrial samples, but
      was highly expressed in decidual tissue. Placental tissue was highly positive.
      GLUT1 mRNA could be detected in endometrial samples with an increase in
      endometria of the late secretory phase (day 25-28) and maximum concentration in
      the decidua of the 9th-10th week of gestation. Our results show that GLUT1 is
      differentially expressed in the different phases of the human endometrium with a
      maximum in the human decidua. Therefore, GLUT1 may be an important marker for
      endometrial differentiation.

PMID- 11447735
TI  - Estrogenic and antiestrogenic effects of raloxifene on collagen metabolism in
      breast cancer MCF-7 cells.
AB  - We compared the effects of different concentrations of raloxifene (1, 4 and 10
      microM) on collagen biosynthesis, gelatinolytic and prolidase activities and
      matrix metalloproteinase (MMP) expression (MMP-2 and MMP-9) in estradiol
      stimulated (2 nM) breast cancer MCF-7 cells. Raloxifene inhibited in a dose
      dependent manner the proliferation of MCF-7 cells, independently of the presence
      or absence of estradiol in the growth medium. Raloxifene at concentrations of 1
      microM and 4 microM inhibited collagen biosynthesis by about 10-fold and
      prolidase activity by about 50%, while at a concentration of 10 microM it
      inhibited these processes by only about 25%. This phenomenon was accompanied by
      differences in gelatinolytic activity and MMP (MMP-2 and MMP-9) expression as
      demonstrated by zymography and Western immunoblot analysis, respectively. In
      estrogen-stimulated MCF-7 cells, cultured in the presence of 1 microM raloxifene,
      a dramatic increase in the activity of both collagenases was found. In contrast,
      addition of raloxifene at a concentration of 10 microM to the medium of the cells
      resulted in restoration of gelatinolytic activity to that found in control cells.
      Similarly, but at both doses (1 and 10 microM), raloxifene was able to reduce MMP
      2 expression in the cells. However, when used alone (without estradiol) a
      concentration of 1 microM raloxifene strongly stimulated MMP-2 expression, while
      at a concentration of 10 microM the effect was not observed. In the case of MMP
      9, only trace amounts of this gelatinase were detected, although in contrast to
      MMP-2, an increase in its expression was noticed at a concentration of 10 microM
      raloxifene. The data raise the possibility that in estrogen-stimulated MCF-7
      cells, raloxifene at low concentrations (1 and 4 microM) evokes antiestrogenic
      effect on collagen biosynthesis and prolidase activity on the one hand, and an
      estrogenic effect on gelatinolytic activity on the other, while at higher
      concentrations (about 10 microM) it evokes an estrogenic effect on collagen
      biosynthesis and prolidase activity, and an antiestrogenic effect on
      gelatinolytic activity. Our data suggest that the effects of raloxifene on
      collagen synthesis, prolidase and metalloproteinase activities in breast cancer
      may explain its role in the prevention of breast cancer development.

PMID- 11447736
TI  - Correctly timed coasting reduces the risk of ovarian hyperstimulation syndrome
      and gives good cycle outcome in an in vitro fertilization program.
AB  - One hundred and twelve severely overstimulated in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients were treated
      with coasting when estradiol concentration was > 3000 pg/ml and the leading
      follicles had attained > or = 18 mm in diameter. Gonadotropin withholding was
      offered to them as a promising method for the prevention of both cycle
      cancellation and complications associated with severe ovarian hyperstimulation
      syndrome (OHSS). The duration of prolonged coasting prior to human chorionic
      gonadotropin (hCG) administration ranged from 2 to 9 days (mean 3.5). hCG was
      administered when the serum estradiol dropped to < 3000 pg/ml and at least three
      growing follicles > or = 20 mm in diameter were present. Fertilization failure
      was noted in six couples and in another 10 cases freezing of all embryos was
      decided, therefore embryo transfer was performed on 96 patients. There were 31
      clinical pregnancies (five twins) giving a pregnancy rate per patient and per
      embryo transfer of 30.4% and 32.3%, respectively, with an implantation rate of
      18.1%. With regard to all 112 coasted patients, six developed moderate and two
      severe OHSS. This study shows that withholding gonadotropin administration in
      high-risk IVF patients results in a good cycle outcome and a very low risk of
      severe OHSS, and also demonstrates the importance of both the timing of coasting
      initiation and the timing of hCG administration.

PMID- 11447737
TI  - Regression of ovarian enlargement in pharmacological ovulation induction.
AB  - The aim of the present study was to determine a possible relationship between
      ovarian functionality and regression of ovarian enlargement according to the
      different categories and degree of severity of ovarian hyperstimulation syndrome
      (OHSS). Among a group of sterile woman (n = 111), two subgroups were studied:
      group A (n = 15), patients affected by severe syndrome; and group B (n = 96),
      patients with massive ovarian enlargement only. The protocol of ovarian
      stimulation was conducted in various in vitro fertilization (IVF) centers;
      ultrasonographic examination and hematological checks were carried out daily;
      patients with severe OHSS were hospitalized. In women of group A, severe symptoms
      disappeared in 7-11 days; in nine patients with regular cycles ovary size
      returned to normal in about 30-40 days, whereas in six subjects with anovulatory
      cycles, the resolution was recorded in about 50-60 days; serum estradiol returned
      to physiological levels within 20-30 days. Women of group B showed a spontaneous
      regression at different times: in 43 subjects that presented regular ovulatory
      cycles, the resolution was recorded in about 30-40 days, whereas in 36 women with
      anovulatory cycles before pharmacological induction, resolution occurred in 50-60
      days, and in 17 cases with polycystic ovary syndrome before pharmacological
      ovulation, an incomplete resolution was obtained; serum estradiol levels returned
      to a physiological range within 20-30 days. Our results show that in patients
      with regular ovulatory cycles, resolution of symptoms is obtained in a shorter
      time than in patients with anovulatory cycles before pharmacological induction.

PMID- 11447738
TI  - Papillary carcinoma of the thyroid arising in struma ovari--report of a case and
      review of management guidelines.

PMID- 11447739
TI  - Clear cell odontogenic carcinoma. Report of two cases and review of the
      literature.
AB  - This study reviews the literature and reports on the morphologic and
      immunophenotypic features of 2 clear cell odontogenic carcinomas occurring in the
      mandible of elderly women, showing extensive infiltration into adjacent tissues.
      The tumor cells were large, with clear cytoplasm, and arranged in irregular
      sheets. Some of the latter demonstrated a peripheral rim of cells with
      eosinophilic cytoplasm or included duct-like structures. There was no evidence of
      ameloblastic differentiation. Most cells contained glycogen granules and were
      immunoreactive for cytokeratins and epithelial membrane antigen. In the
      differential diagnosis other clear cell odontogenic, salivary gland, and
      metastatic tumors should be considered. Both cases were treated with surgical
      excision, and the patients are free of disease after 3 and 5 years, respectively.
      In the literature, however, variable behavior of these tumors has been reported,
      including recurrence and metastases. It is recommended that terms such as clear
      cell ameloblastoma and clear cell odontogenic tumor not be used to describe such
      tumors.

PMID- 11447740
TI  - Expression of vascular endothelial growth factor (VEGF) and VEGF receptor Flk-1
      in benign, premalignant, and malignant prostate tissue.
AB  - Vascular endothelial growth factor (VEGF) is one of the most potent mitogenic,
      highly specific tumor angiogenic factors, which acts via binding to 2 specific
      tyrosine kinase receptors. There are few studies analyzing VEGF receptor
      expression in prostate cancer cells, and results are contradictory. In an
      immunohistochemical study, we analyzed VEGF and VEGF receptor fetal liver kinase
      (Flk)-1 expression in benign glands, high-grade prostatic intraepithelial
      neoplasia (HGPIN), and prostatic carcinomas of different Gleason scores, obtained
      from 21 radical prostatectomy specimens. In all benign glands, VEGF and Flk-1
      expression was confined almost exclusively to the basal cell layer (proliferative
      cell compartment). In HGPIN, labeling was no longer confined to the basal cell
      layer, but also was seen in all neoplastic secretory cells. All carcinomas
      stained positive for both markers. There was a trend for increasing labeling
      intensity with increasing cellular dedifferentiation. We concluded that tumor
      growth stimulated by the VEGF-Flk-1 system is promoted not only by
      neoangiogenesis, but also by tumor cell autostimulation. The VEGF-Flk-1 system
      may have an important role in the process of malignant transformation and tumor
      progression.

PMID- 11447741
TI  - Terminal deoxynucleotidyl transferase-positive cells in human tonsils.
AB  - To study the possible cellular origin of recently recognized indolent terminal
      deoxynucleotidyl transferase (TdT)-positive T-lymphoblastic proliferations of the
      tonsils and oropharynx, we studied normal human tonsils for the presence of TdT
      positive cells. TdT-positive cells were readily demonstrated in the tonsils from
      15 children and adults by immunohistochemical staining. TdT-positive cells were
      distributed in discrete foci at the periphery of lobules of lymphoid tissue and
      adjacent to fibrous septa and had the morphologic features of small to medium
      sized lymphocytes. Double-antibody staining indicated the TdT-positive cells had
      the phenotype of uncommitted early lymphoid precursors (CD3-, CD79a-, CD10-).
      Foci of TdT-positive cells were not identified in 6 reactive lymph nodes studied
      as controls. These studies indicate that tonsils, like bone marrow and thymus,
      are sites of lymphopoiesis. The presence of TdT-positive precursor cells in human
      tonsils may be a factor in the pathogenesis of recently described indolent T
      lymphoblastic proliferations involving the tonsils and oropharynx. The presence
      of TdT-positive cells in human tonsils should not be misinterpreted as evidence
      of lymphoblastic lymphoma or leukemia.

PMID- 11447742
TI  - Decreased CD44 standard form expression correlates with prognostic variables in
      ovarian carcinomas.
AB  - Expression of CD44 standard form (CD44s) was evaluated by automated
      immunohistochemical analysis using the anti-CD44 A3D8 clone in 101 ovarian
      epithelial neoplasms including 82 primary tumors (64 carcinomas and 18 tumors of
      low malignant potential [LMP]), 9 lymph node metastases, 8 malignant ascites, and
      2 peritoneal implants. Immunostaining was scored semiquantitatively. Tumors were
      graded according to the FIGO (International Federation of Gynecology and
      Obstetrics) classification system. Tumor stage and patient survival were
      determined from the patient records. While 9 of 18 LMP tumors expressed CD44s,
      only 15 of 64 carcinomas expressed it. In the carcinomas, univariate analysis
      revealed that decreased CD44s expression correlated with high tumor grade,
      advanced stage, and shortened survival. Loss of CD44s expression also was noted
      in the tumor cells in 8 of 9 lymph node metastases, 7 of 8 malignant ascites, and
      1 of 2 implants. Multivariate analysis revealed that only tumor stage
      independently correlated with patient survival. Loss of CD44s expression
      determined by immunohistochemical analysis is more common in ovarian carcinomas
      than in LMP tumors; correlates with prognostic variables including tumor grade,
      stage, and survival; and may have an important role in the dissemination of
      ovarian cancer.

PMID- 11447743
TI  - Immunohistochemical expression of human erythrocyte glucose transporter and fatty
      acid synthase in infiltrating breast carcinomas and adjacent typical/atypical
      hyperplastic or normal breast tissue.
AB  - To evaluate the immunohistochemical expression of GLUT1, human erythrocyte
      glucose transporter 1, and fatty acid synthase (FAS), 66 human breast carcinomas
      and adjacent peritumoral tissue were studied. GLUT1 and FAS were expressed in 53
      and 61 carcinomas, in 17 and 14 typical/atypical hyperplastic tissues, and in 16
      and 13 tissues adjacent to tumor normal breast tissue, respectively. Statistical
      analysis revealed association between invasive carcinomas, invasive carcinomas
      with in situ component and GLUT1 immunostaining. GLUT1 staining was associated
      with tumor grade, FAS with tumor stage, and GLUT1 and FAS coexpression with tumor
      grade. Controls expressed no immunostaining. GLUT1 and FAS are new markers
      involved in the biologic activities of cancer cells. GLUT1 and FAS coexpression
      may indicate increased use of energy by the neoplastic cells correlated with
      poorly differentiated features and aggressive behavior. The innovative finding
      that GLUT1 and FAS are observed in mammary carcinoma adjacent nonneoplastic
      tissues may suggest a role in detecting initial phases of breast carcinogenesis.

PMID- 11447744
TI  - Chemical typing of amyloid protein contained in formalin-fixed paraffin-embedded
      biopsy specimens.
AB  - The human amyloidoses represent a heterogeneous group of disorders characterized
      by the deposition of fibrillar protein in vital organs. Given the fact that at
      least 20 different molecules can form fibrils, the unambiguous identification of
      the type of amyloid deposited is critical to the correct diagnosis and treatment
      of patients with these disorders. Heretofore, this information has been inferred
      from particular clinical features of the disease, ancillary laboratory tests, and
      results of immunohistochemical analyses. However, to establish unequivocally the
      kind of protein that is deposited as amyloid, it is necessary to determine its
      chemical composition through amino acid sequencing or mass spectroscopy of
      material extracted from fibrillar deposits. We have developed a micromethod
      whereby such studies can be performed readily using sections of formalin-fixed,
      paraffin-embedded biopsy specimens. The ability to identify precisely the nature
      of the tissue deposits has diagnostic, therapeutic, and prognostic implications
      for patients with amyloid-associated disorders.

PMID- 11447745
TI  - Human papillomavirus-16 E6 variants in cervical squamous intraepithelial lesions
      from HIV-negative and HIV-positive women.
AB  - We studied 48 human papillomavirus (HPV)-16-positive squamous intraepithelial
      lesions (SILs) from HIV-negative patients (16 low-grade SILs [LSILs]; 32 high
      grade SILs [HSILs]) and 13 HPV-16-positive SILs from HIV-positive patients with
      AIDS (1 LSIL; 12 HSILs). After HPV typing, the entire HPV-16 E6 coding region was
      amplified and sequenced in all samples. We detected 12 HPV-16 E6 prototypes and 4
      variants among the LSILs in HIV-negative patients, and 15 HPV-16 E6 prototypes
      and 17 HPV-16 variants in the HSIL group. The most prevalent variant of SIL types
      was European 350G, present in 3 and 13 cases, respectively. In 3 HSILs and no
      LSILs we found mixed infection by an HPV-16 E6 prototype and a variant. Two
      variants (1 each in LSIL and HSIL) were of non-European lineage. The only LSIL in
      HIV-positive patients had an HPV-16 E6 prototype; in the HSILs, we found 8 HPV-16
      E6-prototypes, 4 with mixed infection with HPV-31 and 4 variants, all European
      350G. The higher proportion of HPV-16 E6 variants in HSIL than in LSIL in HIV
      negative patients suggests a greater risk of progression. However, further
      studies are needed.

PMID- 11447746
TI  - Intratumoral fasciitis-like change in a gastric smooth muscle tumor after fine
      needle aspiration.

PMID- 11447747
TI  - A novel four-color PCR assay to assess T-cell receptor gamma gene rearrangements
      in lymphoproliferative lesions.
AB  - We describe a novel 4-color polymerase chain reaction (PCR) assay combined with
      GeneScan analysis to assess for T-cell receptor gamma chain gene (TCRgamma)
      rearrangements and evaluate its usefulness in 86 lymphoproliferative lesions. In
      this assay, each variable region (Vgamma) family primer is 5' end-labeled with a
      different fluorescent dye, allowing determination of the Vgamma family involved
      in each TCRgamma rearrangement. PCR products were analyzed by capillary
      electrophoresis. We detected clonal TCRgamma rearrangements in 60 (98%) of 61 T
      cell lymphomas, 2 (15%) of 13 B-cell lymphomas, and 3 (25%) of 12 reactive
      lesions. These results compared favorably with conventional PCR methods using
      denaturing gradient gel electrophoresis, which revealed clonal TCRgamma
      rearrangements in 37 (90%) of 41 T-cell lymphomas, 1 (25%) of 4 B-cell lymphomas,
      and 2 (25%) of 8 reactive lesions. This 4-color PCR assay is at least equivalent
      to conventional PCR methods and is convenient, allows accurate size determination
      of TCRgamma rearrangements, and identifies the specific Vgamma family involved,
      providing more specific information about TCRgamma rearrangement.

PMID- 11447748
TI  - Myeloperoxidase immunoreactivity in adult acute lymphoblastic leukemia.
AB  - To evaluate the frequency and significance of myeloperoxidase positivity in adult
      acute lymphoblastic leukemia (ALL), bone marrow biopsy material from 82 adults
      with ALL was evaluated with a polyclonal myeloperoxidase (pMPO) antibody.
      Nineteen cases (23%) demonstrated evidence of pMPO immunoreactivity. Positive
      cases were precursor B-cell lineage, and CD13 or CD15 expression was more
      frequent than in the pMPO-negative cases. A subset of pMPO-positive cases studied
      with a monoclonal MPO antibody was negative. Western blot analysis using the pMPO
      antibody showed the expected 55-kd band for myeloperoxidase in pMPO-positive and
      pMPO-negative ALLs, suggesting a lack of specificity of this antibody in ALL.
      Forty-two percent (8/19) of the pMPO-positive ALL cases demonstrated evidence of
      t(9;22) by either karyotype or polymerase chain reaction analysis. The pMPO
      positive ALLs had a lower frequency of extramedullary disease than the pMPO
      negative group and a trend toward improved overall survival compared with the
      pMPO-negative group. Immunoreactivity with pMPO in adult ALL may lead to an
      incorrect interpretation of biphenotypic acute leukemia using a recently
      described scoring system, and a revision to that scoring system is proposed to
      accommodate pMPO-positive ALL.

PMID- 11447749
TI  - Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia associated with Hodgkin
      disease. A report of two cases.
AB  - Although the clinical course of lymphoplasmacytic lymphoma (LPL)/Waldenstrom
      macroglobulinemia (WM) is usually indolent, high-grade non-Hodgkin lymphoma may
      develop in a small subset of patients. We have not found any patients with LPL/WM
      associated with Hodgkin disease (HD) described in the literature, prompting us to
      report 2 cases. In case 1, the patient had LPL/WM involving bone marrow diagnosed
      1 week before left supraclavicular lymph node biopsy revealed LPL/WM and
      classical HD. In case 2, the patient had a 15-year history of LPL/WM before
      classical HD developed involving bone marrow, liver, and lymph node. Both cases
      were positive for IgM, monotypic immunoglobulin light chain, and B-cell antigens
      and were CD3-. The neoplastic Hodgkin cells were CD15+, CD20+ (case 1), CD30+,
      CD3-, and CD45- and were negative for Epstein-Barr virus RNA. Both patients were
      treated with chemotherapy for HD. In case 1, clinical response was excellent with
      no histologic evidence of HD in subsequent biopsy specimens. In case 2, HD was
      progressive at last follow-up, despite therapy. Patients with LPL/WM, similar to
      patients with other types of low-grade B-cell lymphoma, can develop HD that may
      respond to chemotherapy.

PMID- 11447750
TI  - Hepatosplenic gamma/delta T-cell lymphoma in immunocompromised patients. Report
      of two cases and review of literature.
AB  - We describe 2 male patients in whom hepatosplenic gamma/delta T-cell lymphoma
      (HSTL) developed 6 and 10 years after renal transplantation. The onset was abrupt
      with systemic symptoms, cytopenia, and hepatosplenomegaly. The histologic
      examination of the spleen (case 1), liver, and bone marrow revealed sinusoidal
      infiltrates of markedly abnormal lymphocytes. The neoplastic cells in these cases
      were CD2+, CD3+, CD4-, CD5-, CD7+, CD8+, CD16+, CD56+, beta F1-negative, and TIA
      1-negative. Both cases displayed clonal rearrangement of the T-cell receptor
      (TCR) delta gene and the TCR beta gene. The spleen in case 1 was positive for
      Epstein-Barr virus genome and showed TCR-gamma gene rearrangement by polymerase
      chain reaction. Isochromosome 7 [i(7)(q10)] was found in each case. Both patients
      died within 4 months of diagnosis. HSTL has been reported in only 5 renal
      transplant recipients. HSTL may be relatively more frequent in immunocompromised
      patients compared with the general population.

PMID- 11447751
TI  - Cytomegalovirus infectivity in whole blood following leukocyte reduction by
      filtration.
AB  - Cytomegalovirus (CMV) may be transmitted by transfusion of whole blood and
      cellular components processed according to standard processing procedures. A need
      exists to develop new procedures to remove CMV and other leukocyte-borne viruses
      from donor blood. Ten patients (AIDS/bone marrow transplants) who were CMV
      antigenemic (virus subsequently confirmed by isolation), donated 50 mL of venous
      blood within 24 to 72 hours of the initial antigen detection. Twenty-five
      milliliter aliquots of each specimen were passed through Purecell Neo Neonatal
      Leukocyte Reduction Filters (Pall, East Hills, NY). The remaining 25-mL
      nonfiltered aliquots, as well as the blood filtrates, were subjected to
      infectivity endpoint determinations. The Purecell Neo filter effected a 3 to 4
      log10 leukocyte reduction. CMV input titers ranged from less than 10 to 7.3 x
      10(1) median tissue culture infectious dose (TCID50) per milliliter. CMV was not
      isolated from any postfiltration effluent (i.e., leukocytes, erythrocytes, or
      plasma). CMV DNA was not detected by nested polymerase chain reaction in 8 of 10
      postfiltrate blood specimens. The Purecell Neo filter was efficacious in
      eliminating or significantly reducing viral (CMV) load in venous blood.

PMID- 11447752
TI  - The role of cysteine and homocysteine in venous and arterial thrombotic disease.
AB  - Hyperhomocysteinemia is a risk factor for arterial and venous thrombosis, whereas
      few data are available on the total cysteine (tCy) levels in thrombophilic
      patients. We studied 82 patients with a previous myocardial infarction (MI; group
      1), 68 patients with a previous deep venous thrombosis (group 2), and 100 control
      subjects (group 3). We assayed total homocysteine (tHcy) and tCy levels by high
      performance liquid chromatography with fluorimetric detection. The odds ratios
      (ORs) for high levels of tCy and tHcy in venous thrombosis and MI were markedly
      increased in group 1 (fasting tCy: OR, 3.6; 95% confidence interval [CI], 1.6
      11.2; postmethionine tCy: OR, 0.97; CI, 0.3-4.0; fasting tHcy: OR, 8.3; CI, 3.9
      18.6; postmethionine tHcy: OR, 12.5; CI, 6.8-27.2) and in group 2 (fasting tCy:
      OR, 2.9; CI, 1.1-7.8; postmethionine tCy: OR, 0.86; CI 0.2-2.6; fasting tHcy: OR,
      8.0; CI 3.6-18.0; postmethionine tHcy: OR, 11.0; CI, 6.0-22.1). Our data suggest
      that plasma tCy levels are a risk factor for venous thrombosis and MI
      independently of tHcy levels and that it may be appropriate to study both
      variables simultaneously to thoroughly study the methionine metabolism.

PMID- 11447753
TI  - Morphologic features suggestive of gluten sensitivity in architecturally normal
      duodenal biopsy specimens.
AB  - We studied small bowel biopsy specimens with architecturally normal villi from 78
      adult patients with potential gluten sensitivity (GS) and correlated them with
      outcome to characterize morphologic features that would allow a pathologist to
      suggest GS. No patient had a previous GS diagnosis. Twelve study patients had GS.
      The mean number of intraepithelial lymphocytes (IELs) per 20 enterocytes from the
      tips of 5 random villi was significantly greater in GS than non-GS biopsy
      samples, but the groups overlapped significantly, making the number
      diagnostically useful only when markedly increased. Crypt mitoses counts had
      similar relationships. Twelve patients had an even distribution of IELs along
      villus sides and over tips (3/66 [5%] non-GS patients, 9/12 [75%] GS patients).
      Non-GS patients had a decrescendo pattern of IELs along the sides of villi.
      Architecturally normal small bowel biopsy specimens with an appreciable,
      continuous, even distribution of IELs along the sides and tips of villi and a
      mean of 12 or more IELs in the tips of several villi are suggestive of GS.
      Pathologists should be watchful for these morphologic features in small bowel
      biopsy specimens to suggest GS.

PMID- 11447754
TI  - Sailing past the horizon. The histologic diagnosis of celiac disease in "nonflat"
      intestinal mucosa.

PMID- 11447755
TI  - Reduced number of CD1a+ cells in cutaneous B-cell lymphoma.
AB  - Cutaneous B-cell lymphoma is difficult to distinguish from pseudolymphoma. The
      histologic pattern and monoclonal restriction (immunohistochemical analysis and
      molecular biology) are the criteria used for differentiating these entities.
      CD1a+ dendritic cells have been observed in the infiltrates of T-cell lymphoma,
      but the presence of these CD1a+ cells has not been compared in B-cell lymphoma
      and pseudolymphoma. We studied the presence of CD1a+ cells on frozen sections of
      23 B-cell lymphomas, 13 pseudolymphomas, and 17 T-cell lymphomas by
      immunohistochemical analysis. We found abundant CD1a+ dendritic cells in only 1
      (4%) of 23 B-cell lymphomas, whereas in 8 (62%) of 13 pseudolymphomas and 17
      (100%) of 17 T-cell lymphomas, strong CD1a staining was present. Our study
      demonstrates a distinct pattern of CD1a staining in the infiltrates of B-cell
      lymphoma and pseudolymphoma that may be of value in the differential diagnosis of
      these skin disorders.

PMID- 11447756
TI  - Multiprobe FISH for enhanced detection of bladder cancer in voided urine
      specimens and bladder washings.
AB  - The aim of this study was to evaluate the UroVysion (Vysis, Downers Grove, IL)
      fluorescence in situ hybridization (FISH) test for improved detection of bladder
      cancer in urinary specimens. Three groups of specimens were examined, including
      voided urine specimens (1) collected before resection of bladder cancer, (2) from
      cystoscopically negative bladders of patients with previous bladder cancer, and
      (3) from patients with benign prostatic hyperplasia (controls). FISH positivity
      was defined as more than 2 urothelial cells with an abnormal signal copy number
      of at least 1 of the 4 probes. FISH was positive in 1 of 27 control specimens and
      in 33 (73%) of 45 pTa, 12 (100%) of 12 pT1, and 13 (100%) of 13 pT2-4 tumors. The
      results were similar in a series of 68 bladder washings. In addition, FISH of
      voided urine specimens was positive in 5 of 10 patients with negative follow-up
      cystoscopy results. Subsequent recurrence was found in 4 of these patients but in
      none of 5 patients with FISH-negative results. Multiprobe FISH markedly improves
      the sensitivity and specificity of cytology for the detection of bladder cancer
      in urine specimens.

PMID- 11447757
TI  - Improved reporting methods for atypia and atypical ductal hyperplasia in breast
      core needle biopsy specimens. Potential for interlaboratory comparisons.
AB  - The incidence of atypia and atypical ductal hyperplasia (ADH) in breast core
      needle biopsies varies widely (900%). I sought to identify methods to reduce the
      dependence of this measure on variability in the patient population. The results
      of all breast core needle biopsies with a diagnosis of ADH or atypia not
      otherwise specified for a 50-month period were reviewed. These were separated
      into different groups by age, and the variability of different reporting methods
      was compared. Of 3,026 cases, 216 were diagnosed as ADH or atypia not otherwise
      specified. The overall incidence of atypia by age group varied significantly from
      0.029 to 0.10. The variability was reduced when atypia was expressed in relation
      to ductal carcinoma in situ (range, 1.0-2.1) or fibrocystic changes (range, 0.15
      0.28). However, variability by age was the least when atypia was expressed in
      relation to the number of cases performed for calcifications (range, 0.13-0.17).
      Variability in atypia rates associated with age is reduced significantly when
      atypia is expressed in relation to the number of biopsies done for
      calcifications. This method of reporting atypia may allow interlaboratory
      comparisons with less dependence on the characteristics of the patient
      population.

PMID- 11447758
TI  - Atypical ductal hyperplasia in breast core needle biopsies. Correlation of size
      of the lesion, complete removal of the lesion, and the incidence of carcinoma in
      follow-up biopsies.
AB  - We reviewed the results of all breast core needle biopsies with a diagnosis of
      atypical ductal hyperplasia (ADH) or atypia not otherwise specified and
      subsequent excisional biopsies for a 50-month period and correlated the results.
      Of 3,026 biopsies, 216 were diagnosed as ADH or atypia not otherwise specified,
      and subsequent resection was available for 105. After review, 95 qualified as
      ADH. Subsequent resection showed ductal carcinoma in situ (DCIS) in 13 excisions,
      ADH in 31, lobular carcinoma in situ in 6, and benign proliferative lesions in
      the remaining 45. In none of the 8 biopsies in which DCIS was found and
      radiographs were available for review was the radiographic lesion entirely
      removed. For comparison, the incidence of carcinoma in resections done for a
      diagnosis of DCIS, low or intermediate grade (solid, cribriform, or
      micropapillary type), on core needle biopsy was significantly greater (8 of 10
      cases). However, the size of the lesions diagnosed as carcinoma also was
      significantly greater than that of the lesions diagnosed as ADH, and in none of
      the 8 biopsies with DCIS at excision was the lesion entirely removed at the time
      of biopsy. The incidence of carcinoma in excisional biopsies done for a diagnosis
      of ADH in core needle biopsies in our institution is relatively low, while the
      incidence of ADH is relatively high. Possible reasons for this include total
      removal of small lesions at the time of biopsy and use of the diagnostic term ADH
      for lesions that are not associated with coexistent DCIS.

PMID- 11447759
TI  - Characterization of human prostate mast cells and their increase in periprostatic
      vein thrombosis.
AB  - Recent data suggest that mast cells (MCs) and their products are involved in the
      pathophysiology of thrombosis. In the present study, we analyzed the number,
      distribution, and phenotype of prostate MCs and periprostatic MCs in patients
      with unilateral periprostatic vein thrombosis (PVT) by immunohistochemical
      analysis and electron microscopy. MCs reacted with monoclonal antibodies to
      tryptase, chymase, and c-kit/CD117 and stained positively for tissue-type
      plasminogen activator (tPA) and urokinase receptor (uPAR/CD87) but did not
      express detectable urokinase (uPA) or plasminogen activator inhibitors (PAI-1,
      PAI-2). We found an increase in the mean +/- SEM number of MCs in PVT compared
      with control (PVT, 14.36 +/- 1.57 vs control, 5.23 +/- 0.57/mm2). The majority of
      MCs accumulated in the adventitia of thrombosed veins and showed a decrease in
      chymase expression. As MCs increase in number in PVT and express a
      profibrinolytic phenotype, we hypothesize that MC-derived molecules have a role
      in endogenous fibrinolysis.

PMID- 11447760
TI  - Retinoblastoma protein partners.
AB  - Studies of the retinoblastoma gene (Rb) have shown that its protein product (pRb)
      acts to restrict cell proliferation, inhibit apoptosis, and promote cell
      differentiation. The frequent mutation of the Rb gene, and the functional
      inactivation of pRb in tumor cells, have spurred interest in the mechanism of pRb
      action. Recently, much attention has focused on pRb's role in the regulation of
      the E2F transcription factor. However, biochemical studies have suggested that
      E2F is only one of many pRb-targets and, to date, at least 110 cellular proteins
      have been reported to associate with pRb. The plethora of pRb-binding proteins
      raises several important questions. How many functions does pRb possess, which of
      these functions are important for development, and which contribute to tumor
      suppression? The goal of this review is to summarize the current literature of
      pRb-associated proteins.

PMID- 11447761
TI  - Nitric oxide-induced apoptosis in tumor cells.
AB  - Nitric oxide (NO), an important molecule involved in neurotransmission, vascular
      homeostasis, immune regulation, and host defense, is generated from a guanido
      nitrogen of L-arginine by the family of NO synthase enzymes. Large amounts of NO
      produced for relatively long periods of time (days to weeks) by inducible NO
      synthase in macrophages and vascular endothelial cells after challenge with
      lipopolysaccharide or cytokines (such as interferons, tumor necrosis factor
      alpha, and interleukin-1), are cytotoxic for various pathogens and tumor cells.
      This cytotoxic effect against tumor cells was found to be associated with
      apoptosis (programmed cell death). The mechanism of NO-mediated apoptosis
      involves accumulation of the tumor suppressor protein p53, damage of different
      mitochondrial functions, alterations in the expression of members of the Bcl-2
      family, activation of the caspase cascade, and DNA fragmentation. Depending on
      the amount, duration, and the site of NO production, this molecule may not only
      mediate apoptosis in target cells but also protect cells from apoptosis induced
      by other apoptotic stimuli. In this review, we will concentrate on the current
      knowledge about the role of NO as an effector of apoptosis in tumor cells and
      discuss the mechanisms of NO-mediated apoptosis.

PMID- 11447762
TI  - Detection of minimal residual disease.
AB  - A high percentage of patients with leukemia, lymphoma, and solid tumors achieve a
      complete clinical remission after initial treatment, but the majority of these
      patients will finally relapse from residual tumor cells detectable in clinical
      remission only by the most sensitive methods. The in vitro amplification of tumor
      specific DNA or RNA sequences by polymerase chain reaction (PCR) allows
      identification of a few neoplastic cells in 10(4) to 10(6) normal cells.
      Depending on the underlying malignant disease and therapeutic treatment, the
      presence of residual tumor cells in an individual patient may herald relapse, but
      a long-term stable situation or slowly vanishing tumor cells are also possible.
      Molecular monitoring of residual leukemia and lymphoma cells by quantitative PCR
      techniques has provided important information about the effectiveness of
      treatment and the risk of recurrent disease as shown by minimal residual disease
      (MRD) analysis in patients with various malignant diseases. Such diseases include
      childhood acute lymphoblastic leukemia, after induction therapy; acute
      promyelocytic leukemia, during and after chemotherapy; and chronic myelogenous
      leukemia, during treatment with alpha-interferon and after allogeneic bone marrow
      transplantation. Evaluation of the predictive value of the detection of MRD has
      to take into account its evolution and course, the pathogenesis, biology, and
      natural course of the underlying malignant disease, the molecular genetic lesion,
      and finally, the type of treatment. Quantification of minimal residual cells by
      the recently developed real-time quantitative PCR technique will surely have a
      major impact on our therapeutic strategies for patients with leukemia, lymphomas,
      and solid tumors. Based on quantitative PCR data, the terms molecular remission
      and molecular relapse have to be exactly defined and validated in prospective
      clinical trials to assess the biological and clinical significance of MRD in
      various types of malignancies.

PMID- 11447763
TI  - Modeling prostate cancer in the mouse.

PMID- 11447764
TI  - Immunity to oncogenic human papillomaviruses.
AB  - The establishment of human papillomavirus (HPV) infection as a major cause of
      several human cancer forms, notably cervical cancer, has spurred development of
      prophylactic and/or therapeutic HPV vaccines for prevention of cervical
      neoplasia. Knowledge of the immunity to HPV forms the basis for such endeavors.
      METHOD: A literature review of humoral and cellular immunity to HPV. The overview
      on human leukocyte antigen (HLA) and cervical cancer was expanded to a formal
      metaanalysis, where relevant articles were located by Medline search and citation
      analysis and graded by preassigned quality criteria on study design. RESULTS: The
      antibody response to the HPV particle is dominated by a neutralizing antibody
      response to a typespecific, conformationally dependent immunodominant epitope.
      Vaccines based on viral particles lacking the viral genome (virus-like particles,
      VLPs) have been highly successful in preventing and treating HPV infection in
      several animal model systems. In humans, the serum antibody response to VLPs is
      stable over time, also after the HPV infection has been cleared, resulting in HPV
      serology being used as a marker of cumulative HPV exposure in spite of the fact
      that a significant proportion of HPV-exposed subjects fail to seroconvert. More
      than 90% of HPV infections will clear spontaneously. The factors that determine
      whether an HPV infection is cleared or persists and increases the risk for cancer
      are not known, but cellular immunity is implicated. Several HLA class II
      haplotypes are associated with cervical cancer: DQw3 increases and DR13 decreases
      the risk for cervical cancer in general (odds ratios (OR) and 95% confidence
      intervals (CI): 1.25(1.15-1.37) and 0.69 (0.56-0.85), respectively); DR15
      increases the risk for HPV16-carrying cancer (OR: 1.47; CI: 1.20-1.81); and DR7
      may be either protective or increase the risk. Most cervical cancers have
      downregulated the expression of at least one HLA class I antigen, whereas class
      II expression is increased in infected epithelium. A Th2 cytokine profile is
      associated with progression to cervical cancer. HPV-antigen-specific
      proliferative responses have been detected in many studies, although it is not
      entirely clear whether these responses are HPV type specific or may be cross
      reactive between HPV types. Specific cytotoxic T lymphocyte (CTL) responses were
      originally reported in only a minority of infected subjects, typically cancer
      patients, but with advancing technology, specific CTLs can be stimulated from
      about half of the women with HPV-carrying disease. In animal model systems, CTL
      responses can mediate clearance. CONCLUSION: The antibody response to HPV is a
      mediator of type-specific protective immunity, which forms the basis for
      prophylactic vaccine candidates. The cellular immunity to HPV is implicated as an
      important factor in cervical carcinogenesis, but the main targets and types of
      responses that mediate HPV clearance are not established.

PMID- 11447765
TI  - p53-dependent apoptosis pathways.
AB  - The p53 tumor suppressor limits cellular proliferation by inducing cell cycle
      arrest and apoptosis in response to cellular stresses such as DNA damage,
      hypoxia, and oncogene activation. Many apoptosis-related genes that are
      transcriptionally regulated by p53 have been identified. These are candidates for
      implementing p53 effector functions. In response to oncogene activation, p53
      mediates apoptosis through a linear pathway involving bax transactivation, Bax
      translocation from the cytosol to membranes, cytochrome c release from
      mitochondria, and caspase-9 activation, followed by the activation of caspase-3, 
      6, and -7. p53-mediated apoptosis can be blocked at multiple death checkpoints,
      by inhibiting p53 activity directly, by Bcl-2 family members regulating
      mitochondrial function, by E1B 19K blocking caspase-9 activation, and by caspase
      inhibitors. Understanding the mechanisms by which p53 induces apoptosis, and the
      reasons why cell death is bypassed in transformed cells, is of fundamental
      importance in cancer research, and has great implications in the design of
      anticancer therapeutics.

PMID- 11447766
TI  - Von Hippel-Lindau disease: clinical and molecular perspectives.
AB  - Von Hippel-Lindau (VHL) disease (MIM 193300) is the most common cause of familial
      clear cell renal cell carcinoma (RCC). VHL disease results from germline
      mutations in the VHL tumor suppressor gene and is characterized by variable
      expression and the development of benign and malignant neoplasms in multiple
      organs. The clinical management of VHL disease is challenging and requires a
      coordinated multidisciplinary approach. However, early detection of VHL tumors by
      annual surveillance has improved the prognosis for VHL gene carriers. Complex
      genotype-phenotype correlations for the major manifestations of VHL disease
      result from allelic heterogeneity and suggest that the VHL gene product has
      multiple and tissue-specific functions. Recent studies suggest that the VHL
      protein represents the adaptor unit of an Skp1-Cdc53/Cul1-F-box (SCF)-like
      protein complex which targets specific proteins for ubiquitinylation and
      proteolysis. Tumors from VHL patients and sporadic tumors with VHL gene
      inactivation (e.g., most clear cell RCC) are hypervascular and overexpress
      hypoxia-inducible mRNAs such as vascular epithelial growth factor (VEGF).
      Recently, pVHL has been shown to regulate proteolysis of the transcription
      factors HIF-1 and HIF-2 (EPAS). Thus absence or inactivation of pVHL leads to
      constitutive HIF-1 and HIF-2 expression, which activates transcription of VEGF
      and other hypoxia-inducible mRNAs. Evidence for further pVHL functions including
      roles in fibronectin metabolism and cell cycle regulation has also been reported,
      but it is unclear whether these functions are mediated via pVHL-targeted
      proteolysis or other mechanisms. Clinical and laboratory studies of VHL disease
      have provided a paradigm for demonstrating the importance of familial cancer
      syndromes in elucidating mechanisms of tumorigenesis in familial and sporadic
      cancer.

PMID- 11447767
TI  - Inhibitory effect of sofalcone on tumor necrosis factor-alpha and interleukin-1
      beta production in human monocytes stimulated by Helicobacter pylori water
      extract.
AB  - We investigated the effect of sofalcone, a synthetic flavonoid derivative of
      sophoradin, on tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta
      production in human monocytes stimulated by Helicobacter pylori water extract. H.
      pylori water extract significantly stimulated TNF-alpha and IL-1 beta production
      by monocytes while incubation with sofalcone (10 micrograms/ml and 50
      micrograms/ml) significantly inhibited this increase in TNF-alpha and IL-1 beta
      production. These results suggest that sofalcone could be used to improve H.
      pylori-associated gastric mucosal inflammation through inhibition of
      proinflammatory cytokine production.

PMID- 11447768
TI  - In vitro activity of levofloxacin against coagulase-positive and -negative
      staphylococci.
AB  - The in vitro activity of levofloxacin compared with that of ciprofloxacin,
      ofloxacin and norfloxacin were examined by conventional in vitro tests against
      150 clinical isolates of staphylococci, subdivided according to species and
      susceptibility to methicillin. Although the minimum inhibitory concentrations
      (MICs) of all quinolones were highest in methicillin-resistant Staphylococcus
      aureus strains, the activity of levofloxacin was almost complete in methicillin
      resistant S. epidermidis and methicillin-resistant S. haemolyticus when compared
      with ciprofloxacin and ofloxacin, which showed more than 30% resistance.
      Methicillin-susceptible S. aureus and S. epidermidis strains were susceptible to
      all quinolones with few differences between the antibiotics tested. The minimal
      bactericidal activity of levofloxacin was within the double dilution range of MIC
      values for all strains tested, demonstrating its potent role against
      staphylococci. In time-kill studies, levofloxacin exerted bactericidal activity
      within 3 h against all staphylococci. These in vitro results suggest that
      levofloxacin is a potent fluoroquinolone against coagulase-negative staphylococci
      and that it is both methicillin-susceptible and resistant. Further studies are
      necessary to determine the role of this drug in the treatment of infections
      sustained by these microorganisms.

PMID- 11447769
TI  - Fibromyalgia treatment with intravenous tropisetron administration.
AB  - A prospective, randomized, placebo-controlled, multicenter, double-blind trial in
      fibromyalgia patients demonstrated that peroral daily treatment with 5 mg
      tropisetron for 10 days produced a significant reduction in pain and other
      symptoms. The aim of the present study was to determine whether intravenous
      administration of 2 mg tropisetron daily for a limited period of time would
      produce quicker and more favorable results. In the first cohort 18 fibromyalgia
      patients received a single intravenous injection of 2 mg tropisetron. In the
      second cohort 24 fibromyalgia patients were treated with 2 mg intravenous
      tropisetron daily for 5 days. Pain intensity was measured with the visual analog
      scale and the pain score. Pain at tender and control points (dolorimeter) as well
      as 17 ancillary symptoms before and after treatment were evaluated. Pain
      intensity was followed-up by means of a patient diary until recurrence.
      Dolorimetry revealed that a single intravenous injection of 2 mg tropisetron
      significantly reduced pain and enhanced pain threshold. These effects, however,
      lasted for only a few days. Of 18 patients in the first cohort, only three showed
      no response to therapy. Of the 24 patients in the second cohort, 23 showed pain
      reduction when 2 mg tropisetron was administered daily for 5 days. Pain relief
      lasted for 2 weeks to 2 months in 20 of these patients. Two patients stopped
      filling in the pain diary. Twelve ancillary symptoms such as sleep disturbances,
      fatigue, morning stiffness were also significantly improved by the latter
      treatment. In the global assessment 16 out of 24 patients showed significant
      improvement and seven showed slight improvement. Only one patient experienced no
      improvement. Tolerability was good. In conclusion, intravenous injection of 2 mg
      of the 5-hydroxytryptamine3 receptor antagonist tropisetron once daily for 5 days
      produced a longer-lasting therapeutic effect on fibromyalgia symptoms than did
      peroral daily treatment with 5 mg of this drug. The results achieved are
      currently being evaluated in a randomized, placebo-controlled, double-blind
      trial.

PMID- 11447770
TI  - The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft
      versus host disease in mice.
AB  - VX-497 is the first inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor
      generated in a structure-based drug design program specifically addressing the
      tolerability problems of currently available immunosuppressive drugs. The
      pharmacological activity of the compound has been examined in murine skin
      transplantation and graft versus host disease (GVHD) models. In the skin
      transplant study, trunk skin grafts from Balb/c mice were grafted onto C57Bl/6
      mice. Mice were administered vehicle or VX-497 twice daily until day 10. Mean
      survival of skin grafts on vehicle-treated animals was 9.9 +/- 0.9 days. Graft
      survival was prolonged significantly in animals treated with VX-497 to 13.2 +/-
      1.2 (p < 0.001, Kaplan Meier Log-Rank test) days in the 50 mg/kg group and 13.9
      +/- 1.0 (p < 0.001) days in the 85 mg/kg group. In the GVHD study, 150 x 10(6)
      nonadherent splenocytes from B6 mice were injected intravenously into the F1
      hybrid strain B6DBA/2. Groups of animals (n = 6) were administered vehicle or 50
      or 100 mg/kg VX-497 b.i.d for 8 days. Animals were sacrificed and spleen weights
      and interferon-gamma (IFN-gamma) serum levels were determined by enzyme-linked
      immunosorbent assay. In addition, spontaneous spleen cell proliferation was
      measured using a 3H-thymidine uptake assay. Isografted F1 animals served as
      controls. GVHD developed in the vehicle-treated allografted F1 mice and treatment
      with VX-497 improved all manifestations of the disease significantly. The 2.9
      fold increase in spleen weight in allografted animals was reduced to a 1.6-fold
      increase in the VX-497-treated mice. Serum IFN-gamma levels were increased 54
      fold in the vehicle group while there was a 7.4-fold increase in VX-497-treated
      animals. Spontaneous spleen cell proliferation was increased 9.9-fold in the
      absence of VX-497 and there was a 3.5-fold increase in its presence. Thus, VX-497
      has been shown to be effective in both a skin transplantation and a GVHD model in
      the mouse. The demonstrated pharmacological activity of VX-497 in these murine
      transplantation models warrants further evaluation of the drug in transplantation
      indications.

PMID- 11447771
TI  - Hyperalgesic effect of intrathecally administered interleukin-1 in rats.
AB  - The present study demonstrates that intrathecal injection of interleukin-1 (IL-1)
      in rats at a dose of 50 pg or 500 pg induced a significant hyperalgesic effect in
      the hot-plate test. The hyperalgesia or the altered nociceptive responses were
      not considered to be the result of sensitization to the hot plate, since the
      nociceptive alteration caused by intrathecal administration of IL-1 stopped after
      20 min. The results suggest that IL-1 can affect pain responsiveness in a dose
      dependent manner and that it is able to modulate neuronal functions. Taken
      together, our findings and the data from the literature suggest that IL-1-induced
      hyperalgesia is related not only to the route of administration but also to the
      algesia testing method used.

PMID- 11447772
TI  - Experimental studies on the mechanism of phospholipase C activation by the lipid
      peroxidation products 4-hydroxynonenal and 2-nonenal.
AB  - The effects of three lipid peroxidation end-products, 4-hydroxynonenal (HNE), 2
      nonenal (NE) and nonanal, on phosphoinositide-specific phospholipase C (PL-C)
      activity were studied in HL-60 cells. Enzymatic activity was determined by
      measuring the amounts of inositol-P3 (Ins-P3) produced by the cells incubated at
      37 degrees C in the presence of the various compounds. HNE was shown to activate
      PL-C at concentrations of between 10(-8) and 10(-6) M; 10(-9) and 10(-8) M of NE
      also strongly stimulated PL-C. In contrast, nonanal failed to modify enzymatic
      activity. The concentrations of HNE and NE active on PL-C showed good
      correspondence with those that have been reported to be chemotactic towards rat
      neutrophils. The pretreatment of cells with 1 microM pertussis toxin completely
      prevented the increase of Ins-P3 production induced by HNE and NE. Maximal PL-C
      stimulation was produced by 10 nM NE; the degree of inositol-P3 production
      induced by the simultaneous addition of an equimolar dose of HNE was not
      significantly different from the activity value induced by NE alone, suggesting a
      possible competition between the two compounds. The data indicate that both HNE
      and NE share a common mechanism of action which, as with other better-known
      chemoattractants, involves PL-C activation through a G regulatory protein.

PMID- 11447773
TI  - Induction of heat shock protein synthesis in human skin fibroblasts in response
      to oxidative stress: regulation by a natural antioxidant from rosemary extract.
AB  - Reactive oxygen species have been implicated in the pathogenesis of the severe
      connective tissue damage present in several photodermatologic disorders,
      including drug-induced phototoxicity, porphyrias and photoaging. Oxidative stress
      has been shown to alter the expression of mammalian antioxidant enzymes and to
      enhance numerous transcription factors, including nuclear factor-kappa B, stress
      activated protein kinase and heat shock factor. The latter represents the
      transcription factor for the synthesis of cytoprotective proteins called heat
      shock proteins. In this study, we investigated the role of oxidative stress and
      sulfdryl (SH) groups in the induction of HSP70 in human skin fibroblasts and the
      effect of antioxidants. We found that significant HSP70 induction occurred after
      exposure to HOOH and this was associated with marked perturbation in protein and
      nonprotein SH groups and with a considerable increase in protein carbonyl levels.
      Treatment with a natural antioxidant from rosemary extract provided notable
      protection against stress-induced modifications of cellular SH and carbonyl
      content, maintaining functional levels of cytoprotective heat shock protein 70.
      Our results point to the possible involvement of redox mechanisms in the heat
      shock signal transduction pathway, which may play an important regulatory role in
      the genetic mechanisms of tolerance to oxidative stress. Exogenous
      supplementation of an antioxidant hydrophilic extract from rosemary could have
      cosmetic benefits and may represent an efficient tool to minimize free radical
      induced skin damage.

PMID- 11447774
TI  - Occlusive versus nonocclusive calcipotriol ointment treatment for palmoplantar
      psoriasis.
AB  - Thirty-nine patients with a clinical diagnosis of palmoplantar psoriasis [23
      (58%) males and 16 (42%) females] were included in this study with the aim of
      evaluating the efficacy of occlusive calcipotriol 50 micrograms/mg ointment vs.
      nonocclusive therapy. Patients were randomized to either twice-weekly overnight
      calcipotriol ointment under occlusion or twice-daily topical nonocclusive
      application of the same ointment for 6 weeks. The effect of treatment was
      assessed on the basis of a psoriasis signs score for erythema, thickness and
      scaliness, which was graded from 0 (absent) to 4 (most severe) at the first
      visit, after 2 weeks and at the end of treatment. Analysis of our results showed
      that twice-weekly occlusive calcipotriol ointment was as effective as the twice
      daily application. The mean total score at baseline was 6 for the occlusive group
      and 6.1 for the nonocclusive group. The score decreased to 1.5 in both groups at
      the end of treatment. No significant adverse effects were reported by patients or
      investigators. We conclude that occlusive calcipotriol ointment is effective in
      the treatment of palmoplantar psoriasis and may produce even better results with
      more frequent use, such as application on alternate days.

PMID- 11447775
TI  - Early-morning administration of dexketoprofen-trometamol in morning stiffness
      induced by nodal osteoarthritis of the hands.
AB  - Morning stiffness in osteoarthritis (OA) of the hands is a troublesome symptom
      that deserves attention in many OA patients. The aim of this research was to
      verify the action of oral dexketoprofen-trometamol (50 mg) administered early in
      the morning on morning stiffness in hand OA. Thirty-five patients were compared
      with 19 controls. The degree of morning stiffness, evaluated by means of the
      WOMAC scale for OA stiffness, was significantly diminished 40 min after drug
      administration in treated patients but not in controls. This drug acted rapidly
      and was effective in reducing morning stiffness in OA of the hands.

PMID- 11447776
TI  - Rheologic changes in the synovial fluid of patients with gonarthritis induced by
      intraarticular infiltration of hyaluronic acid.
AB  - The aim of the present study was to evaluate possible changes in synovial fluid
      viscosity in gonarthritic patients treated with intraarticular infiltration of
      hyaluronic acid. Thirty patients with radiologically proven (Stage III Kellgren)
      serious gonarthrosis, local pain and functional limitation were enrolled. All
      patients had reported at least 4-5 episodes of hydrarthrosis during the previous
      12 months. Therefore, two different phases of their illness could be observed: a
      relatively silent phase of hydrarthrosis and a symptomatic phase. According to
      the protocol, one sample of synovial fluid was collected for evaluation of
      baseline viscosity (pretreatment); immediately afterwards, intraarticular
      administration of high molecular weight sodium hyaluronate (one 20 mg vial/week
      for 3 weeks) was initiated. During the entire treatment period and for 3 weeks
      following the end of treatment, intraarticular synovial fluid samples (one sample
      per week for 3 treatment weeks followed by a further 3 weeks as control) were
      collected to perform rheologic assessment and viscosimetric analysis. The results
      of this preliminary study show that exogenous administration of high molecular
      weight sodium hyaluronate induced normalization of hyaluronic acid viscosity
      values in patients with high and low baseline hyaluronic acid viscosity values.

PMID- 11447777
TI  - Angela Bartenbach, my AMI friend.

PMID- 11447778
TI  - The thyroid cartilage. Sternal notch relationship. 1948.
AB  - One of the most exacting demands made of the medical illustrator is the accurate
      delineation of anatomical relationships. In order to incorporate the maximum
      teaching quality in the illustration of a particular condition, the artist
      continually makes comparisons with the normal. By this method he recognizes and
      emphasizes important deviations, and gives to his drawing or model of the
      pathological specimen, the case seen in clinic, or the steps of a surgical
      procedure, its inherent teaching value.

PMID- 11447779
TI  - A neglected geometry for finding perspective.
AB  - A method for dividing quadrilateral spaces is described to assist artists with
      perspective illustrations. Linear perspective, key to realistic drawings, can be
      time-consuming to use, hampering illustrators who need to be efficient to compete
      in today's market. Using this method, art benefits in speed from an overlooked
      geometry based on right triangles. It also fascinates with versatility as it
      presumes to solve two ancient math riddles.

PMID- 11447780
TI  - Adding power to PowerPoint. Add-ons and plug-ins.
AB  - Microsoft's PowerPoint (PPT) has been around for about ten years. It works on
      both the Macintosh and Windows platforms. Many users have a Macintosh at home and
      a Windows PC in the office and files can be easily transferred. Presentations
      magazine estimated that 85 percent of all presentations given in the U.S. last
      year used PPT. These presentations can be done as 35 mm slides, black and white
      or color overhead transparencies, electronic lectures or the software can be used
      to produce pages for Web sites. PPT has become the "Swiss Army Knife" for
      presenters and can be found everywhere. Since PPT has such a large share of the
      marketplace, a secondary market has developed to cater to PPT users who need
      something that didn't come in the box. These products are referred to as add-ons
      or plug-ins. They are available as commercial products, shareware or even
      directly from Microsoft. This article will look at several of these add-ons and
      discuss their possible use in a health care media production environment.

PMID- 11447781
TI  - Helping processes in a mutual aid organization for persons with emotional
      disturbance.
AB  - To date, the notion of helpfulness of group processes has been equivocal in
      research on self-help groups. This article argues that findings drawn from the
      participants' subjective appraisals of helpfulness carry meanings different from
      those drawn from the correlational approach. In a mutual aid organization serving
      adults with mental health problems, the study found that, whereas universality,
      self-disclosure, and instillation of hope were the most valued processes, support
      and catharsis were the strongest correlates of benefits of participation. The
      authors propose a two-level hierarchy that distinguishes sustaining and
      beneficial factors. Different sets of factors should constitute the focus of
      facilitation at different stages of group development.

PMID- 11447782
TI  - The class that would not read: utilizing Bion's affect theory in group.
AB  - While Bion's group theory continues to inspire contemporary group
      psychotherapists, his theory of human emotion is not as well known. Bion also
      introduced a system of alphabetical and mathematic symbols to offer a shorthand
      for his epistemology in order to make his ideas accessible, flexible, and
      practical for the working clinician. This article presents aspects of Bion's
      theory and metapsychological shorthand to conceptualize effectual dimensions of
      group process, thinking operations, and countertransference. The constructs
      considered include Klein's paranoid-schizoid and depressive positions; manic
      defenses; basic assumptions; "proto-mental" and "pre-monitory" emotions;
      instinctive drives L, H, and K (plus or minus); beta elements; and alpha
      functioning. With these ideas, the author was able to work through aspects of a
      group experience in which, as leader, he unknowingly found himself at an opposite
      affective pole from the members.

PMID- 11447783
TI  - The persistently neglected sibling relationship and its applicability to group
      therapy.
AB  - Despite the parallel between early sibling experiences and patients' experiences
      of their fellow group members, there is a noticeable dearth of articles directly
      addressing this connection as its main thesis. This article describes the
      fundamental applicability of sibling dynamics to a wide range of group
      experiences and interventions, including the introduction of new members, the
      special case of only children, twinning between group members, and the cotherapy
      relationship. We explore patient dreams, the sources of resistance within the
      profession to the awareness of sibling dynamics, and the therapist's management
      of group boundaries and norms through this lens of sibling dynamics.

PMID- 11447784
TI  - Meeting maturational needs in the group setting.
AB  - Many people who enter treatment with intrapsychic conflicts also bring with them
      developmental deficits. These deficits stem from early environmental failures:
      Parenting figures did not provide needed maturational input, creating a gap that
      leaves the child with developmental deficits in their personality. These, like
      intrapsychic conflicts, engender formidable resistances to progress in treatment.
      This article intends to show that group treatment is ideally suited to the task
      of filling in these emotional voids. To enable members to address the deficit of
      a co-member, the group leader systematically initiates and oversees five basic
      steps.

PMID- 11447785
TI  - Group process and group phenomena on the Internet.
AB  - This article identifies group processes and group phenomena in discussion lists
      on the Internet and examines the differences and similarities with the processes
      in small and large groups. Group dynamics and phenomena, such as boundaries,
      cohesion, transference, scapegoating, and the leader's role are addressed. Large
      group features, such as alienation, vulnerability, and the vast amount of issues
      discussed in parallel are described. There are similarities between the
      discussion list and small groups on issues of cohesion and group norms, and in
      the psychological mechanisms of transference and scapegoating. There are
      differences regarding the contract, boundaries, leaving the group, and extra
      group socialization. Although many of the phenomena described resemble a large
      group, a discussion list on the Internet maintains the illusion of being a small
      group and frequently acts like one. While a virtual therapy group would be
      somewhat different from a real group, it could nonetheless be useful.

PMID- 11447786
TI  - The impact of borderline personality disorder on process group outcome among
      women with posttraumatic stress disorder related to childhood abuse.
AB  - The outcome of a 12-week interpersonal process group therapy for women with
      postraumatic Stress Disorder (PTSD) related to childhood sexual abuse with and
      without borderline personality disorder (BPD) was assessed by comparing three
      naturally occurring treatment conditions: groups that did not have any members
      with borderline personality disorder (BPD-) (n = 18), groups in which at least
      one member carried the diagnosis (BPD+)(n = 16), and a 12-week waitlist (WL) (n =
      15). PTSD, anger, depression, and other symptoms were significantly reduced in
      the BPD- groups. However, the BPD+ and WL conditions did not show any pre- to
      posttreatment improvements. Furthermore, the BPD+ condition showed a significant
      worsening on measures of anger. Analyses within the BPD+ condition indicated that
      women with and without the diagnosis experienced equal posttreatment increases in
      anger problems. These latter results suggest the presence of an anger "contagion"
      effect. That is, women without BPD did well in the BPD- groups but showed
      increased anger similar to the BPD+ women when treated in groups with them.
      Implications for client-treatment matching considerations in PTSD group therapy
      are discussed.

PMID- 11447787
TI  - Group psychotherapy training and effectiveness.
AB  - This study surveyed accredited programs in psychiatry, psychology, and social
      work, replicating and extending previous work in group training. Results detail
      the curriculum, group faculty/student participation, and predicted future therapy
      trends in four different formats of group treatment. The number of group courses
      in the curriculum, the number required, and the percent of students participating
      in these courses significantly varies among the three disciplines, indicating a
      discrepancy among those disciplines responsible for training in group therapy
      regarding the value and role of group training. Consensus does exist among the
      disciplines in forecasting that individual therapy will decrease and group
      treatment will increase, but what programs deliver in their training does not
      coincide with their predicted trends for group therapy use in the future. Ratings
      of the differential effectiveness of the four group modalities vs. individual are
      not consistent with empirical evidence. Results call for consensual clarity,
      accord of values and knowledge, and the integration of science, training, and
      practice across the three disciplines.

PMID- 11447788
TI  - A systems analysis of a failure to test the effectiveness of waiting-list group
      therapy.
AB  - This nonexperimental effectiveness study attempted to evaluate the utility of a
      brief waiting-list group. The setting was a university clinic providing treatment
      for an inner-city population. Health delivery and staff dynamics made it
      difficult to conduct clinical research in this treatment-oriented setting. The
      nonrandom design allowed for patient choice, with few clients attending more than
      two group sessions, thus decreasing its impact. Managed-care pressures decreased
      staff cooperation with our research objectives, resulting in very low return
      rates in testing and follow-up data. A social systems analysis, highlighting
      staff and institutional ambivalence, is used to understand the failure to
      adequately test the effectiveness of waiting-list group therapy. Recommendations
      are offered to investigators who contemplate conducting clinical research with
      limited resources.

PMID- 11447789
TI  - [Randomized studies].

PMID- 11447790
TI  - [Consensus conference: acute pancreatitis].

PMID- 11447791
TI  - [Hepatic resection for breast cancer metastases: results and prognosis (65
      cases)].
AB  - STUDY AIM: To report results of liver resections for breast cancer liver
      metastasis (BCLM) and to evaluate the rate of survival and the prognostic
      factors. PATIENTS AND METHOD: Between 1988 and 1999, 69 patients were operated on
      for BCLM and 65 who had liver resection were analyzed. The selection criteria for
      surgery were: normal performance status and liver function test; radiological
      objective response to chemotherapy (and/or hormonotherapy); in cases of non
      isolated BCLM, complete response of associated metastatic site (usually bone) and
      no brain metastases. The mean age of the 65 patients was 47 (30-70) years. BCLM
      was diagnosed an average of 60 (0-205) months after the initial cancer. The BCLM
      was more frequently solitary (n = 44). The mean diameter was 3.8 (0-12) cm. The
      mean number of cycles of chemotherapy before surgery was 7.5 (3-24). Liver
      resections included major hepatectomy (n = 31): right n = 19, extended left n =
      4, left n = 8, minor hepatectomy (n = 25) and limited resection (n = 9). RESULTS:
      There was no postoperative mortality. The 18% morbidity rate included a majority
      of pleural effusions with two reoperations. The median follow-up was 41 months (6
      100 months). The survival rate after surgery was 90% at 1 year, 71% at 3 and 46%
      at 4 years. Thirteen patients are alive at 4 years. The 36-month survival rate
      differed according to the time to onset of BCLM: 55% before versus 86% after 48
      months (p = 0.01). The other studied factors were not statistically associated
      with survival. The recurrence rate in the remaining liver at 36 months differed
      according to the lymph node status of the initial breast cancer: 40% for N0-N1
      versus 81% for N1b-N2 (p = 0.01) and according to the type of liver resection:
      45% for minor liver resection versus 73% for major (p = 0.02). CONCLUSION:
      Adjuvant liver surgery should be included in multicenter treatment protocols for
      medically-controlled breast cancer liver metastasis.

PMID- 11447792
TI  - [Blunt pancreatic fractures].
AB  - STUDY AIM: The aim of this retrospective study was to report on seven blunt
      fractures of the pancreas and to emphasize the difficulties of their diagnosis
      and treatment as well as their severity. PATIENTS AND METHOD: From October 1995
      to March 2000, seven cases of blunt fracture of the pancreas were observed. The
      diagnosis was immediate in two cases, due to an emergency abdominal CT scan, and
      for the five other patients it was postponed by 4 to 12 days because of the
      frequency and severity of the associated lesions present in five cases out of
      seven. A left splenopancreatectomy was performed in four patients; a late
      necrosectomy with external drainage in two patients; and one patient was not
      operated on. RESULTS: There was one postoperative death due to associated
      cerebral lesions. After left splenopancreatectomy a pancreatic fistula dried up
      in less than a week in two patients. After necrosectomy and drainage, the
      operation was complicated in the two cases because of repetitive abscesses and a
      large and long-lasting pancreatic fistula. CONCLUSION: Blunt fractures of the
      pancreas are rare and serious lesions. The diagnosis is often made during an
      emergency laparotomy for hemoperitoneum or peritonitis. The existence of a canal
      rupture confirmed by transpapillary wirsungography, or better by wirsungo-MRI, is
      a strong arguing point for a left splenopancreatectomy when the patient's state
      allows it. Simple external drainage is only justified when the left
      splenopancreatectomy isn't possible.

PMID- 11447793
TI  - [Suspected acute appendicitis. Role of enhanced helical computed tomography.
      Prospective study of 100 patients].
AB  - AIM OF STUDY: To assess the diagnosis accuracy of helical computed tomography
      (CT) in patients with suspected appendicitis. PATIENTS AND METHODS: This
      prospective study included 100 consecutive patients hospitalized for suspected
      appendicitis. There were 57 men and 43 women with a median age of 30 years
      (range: 17-91). An enhanced helical CT was performed at admission, without
      digestive opacification. Four criteria were interpreted as positive signs for
      appendicitis: appendix enlarged > or = 7 mm, right lower quadrant inflammation,
      stercorolith, and peri-appendicular collection. The patient was managed by the
      surgeon without knowing the result of CT. The final diagnosis was made
      pathologically. RESULTS: Eighty-one patients were operated on laparoscopically
      for suspected appendicitis. Intraoperative diagnosis was corrected in three cases
      and 78 appendectomies were performed (73 histological appendicitis, six normal
      appendix). Final diagnosis was a medical disease in 19 patients. The findings of
      67 CT were interpreted as positive (63 true positive and four false positive) and
      the findings of 33 CT were interpreted as negative (24 true negative, nine false
      negative). Sensitivity was 87%, specificity was 86%, positive predictive value
      was 94%, and negative predictive value was 73%. If the nine false negative cases
      with minimal lesions at pathological examination were considered as true
      negative, the rates would be 100%, 89%, 94%, 100%, respectively. CONCLUSION:
      Enhanced helical CT is a good imaging diagnostic tool for suspected appendicitis.
      It may reduce the number of patients admitted for observation and decrease the
      rate of negative appendectomy.

PMID- 11447794
TI  - [Quality of life of vascular disease patients following amputation].
AB  - STUDY AIM: The purpose of this study was to assess the quality of life following
      lower limb amputation for vascular disease. PATIENTS AND METHODS: Thirty-six
      vascular patients operated on for 40 major amputations were reviewed to assess
      demographic and clinical characteristics, possibilities of prosthesis, perception
      of health problems and social adaptation. These data were correlated with general
      satisfaction and quality of life ratings, using the Nottingham Health Profile.
      RESULTS: The average stay in hospital was 109 days. Thirteen patients (36%) died
      in hospital, 23 others (64%) were discharged, but only ten patients (28%) were
      able to go back home. The global mortality rate at 1 year was 44%. Eighteen
      patients (78%) were initially fitted but only seven (30%) were fully independent.
      Eight patients only (35%) were satisfied at the end of treatment. Patient's
      satisfaction was influenced by the level of his amputation, the presence of
      residual pain and by his mobility, but it was independent of prosthetic
      equipment. CONCLUSION: Quality of life of vascular amputated patients is poor and
      marked by persistent pain and considerable handicaps in mobility, limiting social
      activities and relationship. The patients' satisfaction and quality of life
      appear to be related to their ability to manage social relations. Amputation
      should be considered as the first step towards rehabilitation and not the end of
      the treatment. It is only through a multidisciplinary approach that the quality
      of life of amputated patients can be improved.

PMID- 11447795
TI  - [Quality of life one year after laparoscopic fundoplication is close to that of a
      control group: prospective study].
AB  - AIM OF THE STUDY: Prospective evaluation of the quality of life of patients after
      laparoscopic fundoplication for gastroesophageal reflux disease (GERD). PATIENTS
      AND METHODS: The quality of life of 30 consecutive patients who underwent
      laparoscopic fundoplication was evaluated using the GIQLI (gastrointestinal
      quality of life index) questionnaire, which included 36 items in five different
      areas: digestive symptoms, physical condition, emotional reaction, social
      integration and medical treatment. Seventeen men and 13 women (mean age: 50.2 +/-
      17 years (32-68) were included with a follow-up of at least 1 year and with
      complete data available. The quality of life was evaluated before surgery, and at
      1 month, 3 months, 6 months and 1 year after surgery with a 100% follow-up.
      Thirty healthy volunteers representing an identical population (with respect to
      age, sex, BMI, profession, smoking, etc.) anonymously filled in the same
      questionnaire. The pre- and postoperative GIQLI scores of patients operated for
      GERD were compared with the GIQLI score of the control group. RESULTS:
      Preoperatively, the GIQLI score (87 +/- 9.5) was much lower than that of the
      control group (123.4 +/- 13.6) (p < 0.001). This score significantly improved 3
      months and 1 year after surgery and was comparable to that of the healthy
      population (115.3 +/- 9.6 vs 123.4 +/- 13.6 [ns]). Improvements were reported
      mainly with respect to digestive symptoms and physical condition. Social
      integration was slightly modified. CONCLUSION: The quality of life of patients
      after laparoscopic antireflux surgery was greatly improved and was close to the
      level expected in an healthy population. However, the study demonstrated the
      possible presence of postoperative functional digestive disorders, although these
      symptoms were not considered as being uncomfortable, since the level of
      satisfaction was 96.6% (n = 29).

PMID- 11447796
TI  - [Video-assisted total proctocolectomy with ileoanal anastomosis].
AB  - The indication for laparoscopy in digestive surgery has evolved with the
      development of the laparoscopic material as well its increasingly frequent
      practice in the medical community. Those complex operations such as restorative
      proctocolectomy require a high level of technical skill as well as a specifically
      designed operative approach. The study aim was to report our experience of the
      video-assisted approach to restorative proctocolectomy.

PMID- 11447797
TI  - [Radio-guided resection of residual metastatic lymph node from a previously
      resected neuroendocrine tumor].
AB  - Neuroendocrine tumors are slowly growing and carry a high risk of recurrence.
      Somatostatin receptor scintigraphy is considered as the gold standard for
      preoperative evaluation and postoperative follow-up. The use of an intraoperative
      detection probe makes easier a complete resection of abdominal residual or
      recurrent tumor. These resections may be incomplete because of the small size of
      the tumor and the postoperative adhesions. Radio-guided surgery is recommended in
      order to reduce the need for reoperation.

PMID- 11447798
TI  - [Adenocarcinoma of the anal glands].
AB  - The study aim was to report an adenocarcinoma of the anal glands revealed by an
      anal abscess in a 64-year-old man. Malignant transformation of an anal fistula is
      discussed in the genesis of this disease. Clinical symptoms are not specific.
      Abdomino-perineal resection of the rectum is the usual surgical treatment and
      adjuvant radiation therapy didn't prove its efficiency.

PMID- 11447799
TI  - [Parathyroid cyst].
AB  - The aim of this study was to report two cases of symptomatic and non-functional
      parathyroid cyst, diagnosed with ultrasonography and percutaneous punction and
      treated by surgical resection of the cystic gland.

PMID- 11447800
TI  - [Surgical wounds with or without dressings. Prospective comparative study].
AB  - STUDY AIM: The aim of this study was to compare the infectious local risk when
      the wound dressing was removed or not after 48 hours, and to look for the other
      advantages or disadvantages of these two methods. PATIENTS AND METHOD: Two groups
      of 50 patients who underwent a thoracic or abdominal procedure, class I or II
      according to Altemeier, have been randomly selected: one received a wound
      dressing after 48 hours, and the second did not. RESULTS: The clinical features
      were comparable between the two groups. There was no significant difference in
      the outcome of the two groups of patients in terms of wound infection (only one
      infected wound in each group). CONCLUSION: Wound dressing usually seems
      unnecessary.

PMID- 11447801
TI  - [Antibiotic prophylaxis and surgery. Prescription compliance in Franche-Comte
      with the national reference system].
AB  - AIM OF THE STUDY: To evaluate the practice of antibiotic prophylaxis for surgery
      in the Franche-Comte region of France. MATERIALS AND METHODS: A total of 36
      surgical teams (72 pairs surgeons/anaesthesists) participated in data collection.
      Five variables describing practices concerning antibiotic prophylaxis for surgery
      were compared to national recommendations: did the surgical procedure require
      antibiotic prophylaxis and was it carried out? Was the antibiotic used
      appropriately? Was the timing of the first injection optimal? Was the total
      duration of the treatment correct? Was the dose correct? RESULTS: Among the 687
      operations for which data were collected, 513 (74.7%) that corresponded to class
      1 or 2 Altemeier operations for which the Societe Francaise d'Anesthesie et
      Reanimation (SFAR) had drawn up recommendations were analysed in order to answer
      these questions. The overall frequency of conformity with the regulations was 40%
      for these 513 operations. Of the 156 patients who did not receive the recommended
      antibiotic, 133 (85.5%) received an antibiotic with an activity range wider than
      that of the recommended antibiotic. The duration of prophylaxis was longer than
      recommended in 80 (87.9%) out of the 91 patients for whom the duration of
      antibiotic prophylaxis did not respect the recommendations. CONCLUSIONS: This
      prospective surveillance showed that less than 50% of patients received an
      antibiotic prophylaxis that was conformed to the regulations. To ensure the
      efficiency of prophylaxis and to prevent deleterious effects, such as the
      emergence of antibiotic-resistant bacteria, the recommendations must be regularly
      respected. Frequent audits of practices should be carried out by the teams
      responsible for fighting nosocomial infections.

PMID- 11447802
TI  - [Excerpts from the eulogy of Jean-Louis Petit presented during the public session
      of the Royal Academy of Surgery on May 26 1750 by A. Louis].
AB  - Jean-Louis Petit (1674-1750) was first enthusiastic about anatomy, received a
      master's certificate in surgery in Paris in 1700, became a member of the Royal
      Academy of Sciences in 1715, and was named director of the Royal Academy of
      Surgery by the king when it was created in 1731. He acquired great notoriety
      because of his skill and experience, thanks to his case reports of hemorrhage,
      lacrimal fistula, operation on the frenum, for his treatise on bone diseases and
      especially for his general treatise on surgical operations on which he worked 12
      years and which was finished after his death by F.D. Lesne.

PMID- 11447803
TI  - [Colonic metastasis from a renal cell adenocarcinoma].

PMID- 11447804
TI  - [Ileal duplication revealed by an obstructive syndrome in a young adult].

PMID- 11447805
TI  - [Traumatic rupture of the jejunum not detectable by helical computed tomography].

PMID- 11447806
TI  - [Pneumoperitoneum after arterial chemoembolization for hepatocellular carcinoma].

PMID- 11447807
TI  - [Complicated hydatid cyst of the pancreas after needle biopsy].

PMID- 11447808
TI  - [Intestinal obstruction by a hernia through the foramen of Winslow].

PMID- 11447809
TI  - [Abdominopelvic actinomycosis].

PMID- 11447810
TI  - Motherhood and murder.

PMID- 11447811
TI  - The baby blues and beyond.

PMID- 11447812
TI  - 'I had lost all joy and hope'.

PMID- 11447813
TI  - Profits vs. pain relief.

PMID- 11447814
TI  - Playing god on no sleep.

PMID- 11447815
TI  - What's best for the patient?

PMID- 11447816
TI  - What the fight is about.

PMID- 11447817
TI  - A mother no more.

PMID- 11447818
TI  - Shotgun rides again. Three years after receiving a new liver, a reborn wrestler
      returns to the ring.

PMID- 11447819
TI  - Beware: toxic mold.

PMID- 11447820
TI  - Watching out for a shady deal. Could your sunglasses be giving you permanent eye
      damage? How to shop for the best kind of protection.

PMID- 11447821
TI  - Warning: are you using nonphysicians for MSEs? Rethink this risky practice.
AB  - Using nonphysicians to give patients medical screening examinations (MSEs) has
      resulted in numerous lawsuits, EMTALA violations, and adverse outcomes, yet the
      practice is common in EDs. EMTALA experts advise against using nurses to perform
      MSEs. Educate staff that triage is not a substitute for an MSE. Follow protocols
      strictly and document the adequacy of the scope of the MSE.

PMID- 11447823
TI  - Update your ED staff on AHA guidelines.
AB  - To improve patient care and avoid liability risks, you must ensure your staff are
      practicing according to new guidelines from the American Heart Association. To
      increase staff participation in inservicing, offer continuing education credit,
      provide refreshments, and hold several programs. Use e-mail to alert staff about
      the new guidelines and how to obtain copies. Hold mock codes for nurses,
      physicians, and respiratory therapists to manage patient scenarios.

PMID- 11447824
TI  - Senate confronts the nursing shortage.

PMID- 11447825
TI  - Modulation of beta-amyloid production and fibrillization.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in old age and
      presently affects an estimated 4 million people in the U.S.A. and 0.75 million
      people in the U.K. It is a relentless, degenerative brain disease, characterized
      by progressive cognitive impairment. In the final stages of the disease, patients
      are often bedridden, doubly incontinent and unable to speak or to recognize close
      relatives. Pathological changes of Alzheimer's disease include extensive neuronal
      loss and the presence of numerous neurofibrillary tangles and senile plaques in
      the brain. The senile plaques contain amyloid fibrils derived from a 39-43-amino
      acid peptide referred to as beta-amyloid or A beta. The basic theory of the so
      called 'amyloid hypothesis' is that the deposition of aggregated forms of A beta
      in the brain parenchyma triggers a pathological cascade of events that leads to
      neurofibrillary tangle formation, neuronal loss and the associated dementia [1].
      Here we discuss progress towards the identification of inhibitors of A beta
      production and fibrillization.

PMID- 11447826
TI  - Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms.
AB  - The three common apolipoprotein E (ApoE) alleles differentially contribute to the
      risk of Alzheimer's disease (AD). While the APOE genotype alters susceptibility
      to disease expression, individuals with APOE epsilon 4 alleles have the highest
      risk of developing AD; the APOE epsilon 4 allele is neither essential nor
      sufficient on its own to cause AD. Since the discovery, in 1992, of the
      involvement of APOE in AD, many scientists have explored the role of the ApoE
      isoforms in the central nervous system in an effort to elucidate their roles in
      the pathophysiological mechanism of this disease. While many hypotheses have been
      proposed, none has been proven. ApoE was discovered through investigations into
      cholesterol metabolism. In serum and in cerebrospinal fluid ApoE binds
      lipoprotein particles, which contain cholesterol esters, and is critical in the
      shuttling of cholesterol from cell to cell. Trafficking of ApoE is mediated by
      specific interactions with cell-surface receptors. As described later, several
      families of ApoE receptors with diverse functions have been discovered. The roles
      of these receptors are proving increasingly complex since additional interactions
      with other ligands and with other intracellular proteins are rapidly being
      identified. It was once thought that these receptors only shuttle ApoE-containing
      phospholipid particles from the extracellular environment into the cell, but they
      also transduce a number of additional intracellular signals and interactions.
      Molecular signalling cascades initiated by the various ApoE receptors modulate a
      number of critical cellular processes. To date, two functional classes of ApoE
      receptors have been identified. The first is the low-density lipoprotein receptor
      family and the second the scavenger receptor families.

PMID- 11447827
TI  - Apolipoprotein E gene and Alzheimer's disease: is tau the link?
AB  - The finding that APOE (the gene encoding apolipoprotein E) polymorphic variation
      was associated with an altered risk of developing Alzheimer's disease (AD) was a
      significant advance and immediately prompted a search for the mechanisms
      responsible for this alteration. Some 6 years later, a number of different
      hypotheses remain that might account for this influence on pathogenesis with no
      single mechanism being unequivocally accepted. The different approaches to
      understanding these mechanisms can be broadly categorized as: those suggesting a
      remote effect, such as different rates of vascular risk factors in those with the
      different APOE alleles; those proposing altered neuronal vulnerability, perhaps
      due to apolipoprotein E (ApoE)-isoform-specific differences in local cholesterol
      transport; and those hypotheses postulating an ApoE interaction with the two key
      lesions of AD, plaques and tangles. In this chapter we will review the evidence
      for and against an interaction between ApoE and the neuronal cytoskeleton, in
      particular with the microtubule-associated protein tau.

PMID- 11447828
TI  - Apolipoprotein E and beta A4-amyloid: signals and effects.
AB  - In humans, the apolipoprotein E gene (APOE) is polymorphic with the alleles APOE
      epsilon 2, 3 and 4 coding for apolipoproteins (Apo) E2, 3 and 4. Apart from age,
      the APOE epsilon 4 allele represents the most important risk factor in sporadic
      Alzheimer's disease (AD). Compared to APOE epsilon 3 homozygotes, the
      histopathological onset of tau pathology is found 1-2 decades earlier but
      progresses with the same speed. ApoE dose-dependently and specifically increases
      free intraneuronal calcium levels in the order ApoE4 > ApoE3 > ApoE2. This effect
      is amplified in the presence of beta A4-peptide. The ApoE effects on calcium are
      not affected by the blockade of action potentials with tetrodotoxin, or by
      inhibition of common ApoE binding sites. The calcium channel involved has been
      identified as a P/Q-type-like channel. Brain tissue ApoE levels differ with
      respect to APOE alleles and Braak-stage for Alzheimer-histopathology. The
      production of ApoE in astrocytes is controlled by several receptor/effector
      systems such as adrenoceptors and cAMP. In the presence of beta A4-peptide
      fragments, astrocytes stop their synthesis of ApoE resulting in a massive
      reduction in the bioavailability of ApoE. In the periphery, ApoE directs
      cholesterol transport and thereby influences its cellular concentrations. In
      neurons, changes in the concentration of cholesterol influence the
      phosphorylation status of the microtubule-associated protein tau at sites known
      to be altered in AD.

PMID- 11447829
TI  - Regulation of gene expression by muscarinic acetylcholine receptors.
AB  - In the brain, muscarinic acetylcholine receptors (mAChRs) are involved in higher
      cognitive functions including synaptic plasticity and memory. In Alzheimer's
      disease (AD) patients the cholinergic nervous system is severely damaged. In
      order to reinforce the cholinergic system, clinical tests were started to use
      cholinomimetic drugs to treat AD patients. To identify the genes involved in
      mAChR signalling, we used a differential display approach and found 11 genes that
      were readily activated by mAChR with 1 hour of activation. These included the
      transcription factors Egr-1, Egr-2, Egr-3, c-Jun, Jun-D and Gos-3; the growth
      regulator hCyr61; the signalling factors NGFi-B (nerve growth factor induced gene
      B) and Etr101; the unknown gene Gig-2 (for G-protein-coupled receptor induced
      gene 2); and the acetylcholinesterase gene (ACHE). Our data show that multiple
      immediate-early genes are under the control of mAChRs, and they suggest that
      these genes play important roles in coupling receptor stimulation to long-term
      neuronal responses. The results also suggest a feedback mechanism where up
      regulated ACHE expression and accelerated breakdown of acetylcholine (ACh) at the
      cholinergic synapses limits increases in cholinergic transmission. Three hours
      after m1 mAChR activation a different pattern of gene expression was
      demonstrated. It included the novel genes Gig-3 and Gig-4, as well as the LIM
      only protein LM04. Like ACHE, these genes are target genes which may be under the
      control of the above immediate-early genes. Together, our data show that
      muscarinic receptors induce a complex and sustained pattern of gene expression
      that may be involved in the regulation of cholinergic transmission as well as the
      control of cellular functions in post-synaptic cholinergic target cells. These
      results may contribute to a better understanding of the effects and side effects
      of cholinomimetic treatment in AD patients.

PMID- 11447830
TI  - Oxidative signalling and inflammatory pathways in Alzheimer's disease.
AB  - It is well established that inflammation and oxidative stress are key components
      of the pathology of Alzheimer's disease (AD), but how early in the pathological
      cascade these processes are involved or which specific molecular components are
      key, has not been fully elucidated. This paper describes the pharmacological
      approach to understand the molecular components of inflammation and oxidative
      stress on the activation of microglial cells and neuronal cell viability. We have
      shown that activation of microglia with the 42-amino-acid form of the beta
      amyloid peptide (A beta 42) activates the production of cyclooxygenase-2, the
      inducible form of nitric oxide synthase and tumour necrosis factor-alpha and
      there appears to be little interactive feedback between these three mediators.
      Moreover, we explore the effects of a series of salen-manganese complexes, EUK-8,
      -134 and -189, which are known to possess both superoxide and catalase activity.
      These compounds are able to protect cells from insults produced by hydrogen
      peroxide or peroxynitrite. Moreover, EUK-134 was also able to limit the output of
      prostaglandin E2 from activated microglial cells. The mechanisms underlying these
      effects are discussed. Together, these data support a pivotal role for oxidative
      stress and inflammation as key mediators of the pathological cascade in AD and
      provide some ideas about possible therapeutic targets.

PMID- 11447831
TI  - Alzheimer's disease: inside, outside, upside down.
AB  - Neurotoxicity of beta-amyloid peptide (A beta) in Alzheimer's disease (AD) is
      usually thought to arise from the nonspecific effects of high concentrations of A
      beta on vulnerable neurons, resulting in membrane destabilization and increasing
      intracellular calcium concentration. This review advances the hypothesis that at
      early stages of AD, when A beta is present in lower amounts, its ability to
      perturb the function of cellular targets is mediated by specific cofactors
      present on the cell surface and intracellularly. Receptor for advanced glycation
      endproducts (RAGE) is a cell-surface receptor which binds A beta and amplifies
      its effects on cells in the nanomolar range. The intracellular enzyme A beta
      binding alcohol dehydrogenase (ABAD) is likely to engage nascent A beta formed in
      the endoplasmic reticulum, and to mediate cell stress from this site. The
      analysis of A beta interaction with RAGE and ABAD, as well as other cofactors,
      provides insight into new mechanisms and, potentially, identifies therapeutic
      targets relevant to neuronal dysfunction in AD.

PMID- 11447832
TI  - Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis
      of Alzheimer's disease.
AB  - Endoplasmic reticulum (ER) appears to be a focal point for alterations that
      result in neuronal dysfunction and death in Alzheimer's disease (AD). Aberrant
      proteolytic processing and/or trafficking of the beta-amyloid precursor protein
      (APP) in ER may promote neuronal degeneration by increasing the levels of the
      neurotoxic forms of beta-amyloid (A beta) and by decreasing the levels of the
      neuroprotective secreted form of APP (sAPP alpha). Some cases of AD are caused by
      mutations in the genes encoding presenilin 1 (PS1). When expressed in cultured
      neuronal cells and transgenic mice, PS1 mutations cause abnormalities in ER
      calcium homoeostasis, enhancing the calcium responses to stimuli that activate
      IP3- and ryanodine-sensitive ER calcium pools. Two major consequences of this
      disrupted ER calcium regulation are altered proteolytic processing of APP and
      increased vulnerability of neurons to apoptosis and excitotoxicity. The impact of
      PS1 mutations and aberrant APP processing is particularly great in synaptic
      terminals. Perturbed synaptic calcium homoeostasis promotes activation of
      apoptotic cascades involving production of Par-4 (prostate apoptosis response-4),
      mitochondrial dysfunction and caspase activation. A beta 42 (the 42-amino-acid
      form of A beta) induces membrane lipid peroxidation in synapses and dendrites
      resulting in impairment of membrane ion-motive ATPases and glucose and glutamate
      transporters. This disrupts synaptic ion and energy homoeostasis thereby
      promoting synaptic degeneration. In contrast, sAPP alpha activates signalling
      pathways that protect synapses against excitotoxicity and apoptosis. In the more
      common sporadic forms of AD, the initiating causes of the neurodegenerative
      cascade are less well defined, but probably involve increased levels of oxidative
      stress and impaired energy metabolism. Such alterations have been shown to
      disrupt neuronal calcium homoeostasis in experimental models, and may therefore
      feed into the same neurodegenerative cascade initiated by mutations in
      presenilins and APP. Perturbed synaptic ER calcium homoeostasis and consequent
      alterations in APP processing appear to be pivotal events in both sporadic and
      familial forms of AD.

PMID- 11447833
TI  - Receptor-G-protein signalling in Alzheimer's disease.
AB  - Based on radioligand binding studies, it has long been assumed that the
      neurochemical pathology of Alzheimer's disease (AD) does not involve widespread
      changes in post-synaptic neurotransmitter function. However, more recent studies
      suggest that receptor function in AD may be compromised due to disrupted post
      receptor signal transduction, in particular that mediated by the G-protein
      regulated phosphoinositide hydrolysis and adenylate cyclase (AC) pathways. The
      phosphoinositide hydrolysis pathway has been shown to be altered at a number of
      levels in AD post-mortem brains, including impaired agonist and G-protein
      regulation of phospholipase C, decreased protein kinase C (PKC) levels and
      activity, and a reduced number of receptor sites for the second messenger,
      Ins(1,4,5)P3. Of these, loss of Ins(1,4,5)P3 receptors and PKC in the entorhinal
      cortex and hippocampus correlates with AD-related neurofibrillary changes, as
      staged according to Braak's protocol. Disregulation of the phosphoinositide
      hydrolysis pathway may therefore have consequences for the progression of AD
      pathology. In contrast to the extensive pattern of disruption seen with the
      phosphoinositide hydrolysis pathway, changes to AC signalling in AD appear more
      circumscribed. Disruptions include a lesion at the level of Gs-protein
      stimulation of AC and, at least in the hippocampus, reduced enzyme activities in
      response to forskolin stimulation. Of these, the latter change has been shown to
      precede neurofibrillary changes. Apart from a loss of calcium/calmodulin
      sensitive AC isoforms, other components of this signalling pathway, including G
      protein levels, Gi-protein mediated inhibition and protein kinase A levels and
      activity, remain relatively preserved in the disorder.

PMID- 11447834
TI  - Dysfunctional intracellular calcium homoeostasis: a central cause of
      neurodegeneration in Alzheimer's disease.
AB  - The clinical symptoms of all forms of Alzheimer's disease (AD) result from a
      slowly progressive neurodegeneration that is associated with the excessive
      deposition of beta-amyloid (A beta) in plaques and in the cerebrovasculature, and
      the formation of intraneuronal neurofibrillary tangles, which are composed
      primarily of abnormally hyperphosphorylated tau protein. The sequence of cellular
      events that cause this pathology and neurodegeneration is unknown. It is,
      however, most probably linked to neuronal signal transduction systems that become
      misregulated in the brains of certain individuals, causing excessive A beta to be
      formed and/or deposited, tau to become aggregated and hyperphosphorylated and
      neurons to degenerate. We hypothesize that a progressive alteration in the
      ability of neurons to regulate intracellular calcium, particularly at the level
      of the endoplasmic reticulum, is a crucial signal transduction event that is
      linked strongly to the initiation and development of AD pathology. In this
      chapter we will discuss the key findings that lend support to this hypothesis.

PMID- 11447835
TI  - Transgenic mouse models of Alzheimer's disease: phenotype and mechanisms of
      pathogenesis.
AB  - A range of transgenic mice have been created to model Alzheimer's disease. These
      include mice expressing human forms of the amyloid precursor protein, the
      presenilins and, more recently, tau. Several of the models develop features of
      the disease including amyloid pathology, cholinergic deficits, neurodegeneration
      and cognitive impairment. Progress in the characterization and use of these model
      animals is discussed.

PMID- 11447836
TI  - Modelling Alzheimer's disease in multiple transgenic mice.
AB  - We have reported transgenic mice with neuronal overexpression of the clinical
      mutant beta-amyloid precursor protein (APP) known as London, which develop an AD
      related phenotype [Moechers, Dewachter, Lorent, Reverse, Baekelandt, Nadiu,
      Tesseur, Spittaels, Van den Haute, Checler, et al. (1999) J. Biol. Chem. 274,
      6483-6492]. Characterized early symptoms (3-9 months) include disturbed
      behaviour, neophobia, aggression, hypersensitivity to kainic acid,
      hyposensitivity to N-methyl-D-aspartate, defective cognition and memory, and
      decreased long-term potentiation. Late in life, at 12-15 months, amyloid plaques
      develop in the brain and correlate with increased levels of beta-amyloid (A
      beta)40/42 (the 40- and 42-amino-acid forms of A beta). The formation of amyloid
      plaques is dissociated in time from and not involved in the early phenotype.
      Hyperphosphorylated protein tau is present but no tangle pathology is observed.
      In double-transgenic mice, i.e. APP/London x Presenilin 1, the increased
      production of A beta 42 results in amyloid plaques developing by the age of 6
      months. Transgenic mice with overexpression of either human apolipoprotein E4
      (ApoE4) or human protein tau in central neurons develop severe axonopathy in the
      brain and spinal cord. Progressive degeneration of nerves and muscles is
      demonstrated by motor problems, wasting and premature death. Tau is
      hyperphosphorylated but there is no formation of filaments or neurofibrillary
      tangles. The tangle aspect of AD pathology is still missing from all current
      transgenic amyloid models. Its implementation will require insight into the
      cellular signalling pathways which regulate the microtubule-stabilizing function
      by phosphorylation of neuronal tau.

PMID- 11447837
TI  - The role of post-translational modification in beta-amyloid precursor protein
      processing.
AB  - The beta-amyloid precursor protein (APP) plays a pivotal role in the early stages
      of neurodegeneration associated with Alzheimer's disease. An alteration in the
      processing pattern of the protein results in an increase in the generation of the
      40-42-amino-acid beta-amyloid (A beta) peptide, which coalesces to form
      insoluble, extracellular amyloid deposits. A greater understanding of the factors
      that influence APP processing may assist in the design of effective therapeutic
      agents to halt progression of Alzheimer's disease. APP is a sialoglycoprotein
      with two potential N-linked glycosylation sites, one of which may contain a
      complex oligosaccharide chain. An alteration in the glycosylation state of APP by
      the generation of oligomannosyl oligosaccharides results in a decrease in the
      secretion of the neuroprotective, soluble form of the protein and a parallel
      increase in the deposition of the cellular protein within the perinuclear region
      of the cell. Conversely, the attachment of additional terminal sialic acid
      residues on to the oligosaccharide chain results in an increase in secretion of
      soluble APP (sAPP alpha). One factor that has been widely reported to alter APP
      processing is the activation of protein kinase C (PKC). This process has been
      characterized using synaptosomal preparations, which suggests that the PKC action
      is occurring at the level of the plasma membrane. Furthermore, when cells are
      transfected with the sialyltransferase enzyme, there is a direct relationship
      between the sialylation potential of APP and the fold stimulation of sAPP alpha,
      after PKC activation. These results suggest that the post-translational
      modification of APP by glycosylation is a key event in determining the processing
      of the protein.

PMID- 11447838
TI  - Alzheimer's disease: dysfunction of a signalling pathway mediated by the amyloid
      precursor protein?
AB  - All individuals with Alzheimer's disease (AD) experience a progressive loss of
      cognitive function, resulting from a neurodegenerative process characterized by
      the deposition of beta-amyloid (A beta) in plaques and in the cerebrovasculature,
      and by the formation of neurofibrillary tangles in neurons. The cause of the
      neuronal death is unknown but it is thought to be linked in some way to the beta
      amyloid precursor protein (APP), which is the source of the A beta that
      accumulates in the AD brain. There are two pieces of supporting data for this:
      first, APP is overexpressed in Down's syndrome, which leads to AD-like
      neuropathology by the age of 40 in virtually all affected individuals; secondly,
      specific point mutations in APP cause some forms of familial AD. Our laboratory
      has focused on a specific aspect of APP and its connection with the neuronal
      destruction seen in AD. We have hypothesized that AD results from a progressive
      dysfunction of APP. In addition, on the basis of recent data generated by our
      laboratory and others, we propose that in the normal brain a percentage of APP is
      present as an integral protein of the plasma membrane that mediates the
      transduction of extracellular signals into the cell via its A beta-containing C
      terminal tail. In AD, accumulation of abnormal levels of the C-terminus in the
      neuron disturbs this signal-transduction function of APP, causing disorders in
      the cell-cycle machinery and consequent apoptosis. Here, we discuss the key
      findings that support this hypothesis, and discuss its therapeutic implications
      for AD.

PMID- 11447839
TI  - Genetic dissection of primary neurodegenerative diseases.
AB  - Neurodegenerative diseases have traditionally been defined as clinico
      pathological entities. The clinician observes characteristic clusters of symptoms
      that relate to the anatomical distribution of the lesion. Typically, these
      symptoms progress in a characteristic sequence allowing the clinician to make a
      provisional diagnosis. At autopsy, the pathologist examines the nature and
      distribution of the lesions, reads the clinical report and makes a definitive
      diagnosis. This structure is so deeply embedded in our concepts of
      neurodegenerative disease that we are hardly aware of it. It has become deeply
      embedded because it has been a useful construct that allows grouping of patients
      for research, especially in treatment trials. However this success has served to
      hide its limitations and molecular genetic analysis has clearly shown that there
      are other ways of thinking about neurodegenerative disease. In this review, I
      will summarize the limitations of the clinicopathological approach, and discuss
      how molecular genetics offers an alternative way of thinking about
      neurodegeneration. My intention is not to suggest that we should replace the
      clinicopathological approach (Newtonian physics is a perfectly good way of
      thinking about the world on a day-to-day basis even though we know it is only an
      approximation to the truth) but rather, to suggest that future treatments for
      these most devastating diseases may come from a deeper understanding of their
      related pathogenesis.

PMID- 11447840
TI  - Tau gene mutations and neurodegeneration.
AB  - Abundant neurofibrillary lesions made of the microtubule-associated protein tau
      constitute a defining neuropathological characteristic of Alzheimer's disease.
      Filamentous tau protein deposits are also the defining neuropathological
      characteristic of other neurodegenerative diseases, many of which are
      frontotemporal dementias or movement disorders, such as Pick's disease,
      progressive supranuclear palsy and corticobasal degeneration. It is well
      established that the distribution of tau pathology correlates with the presence
      of symptoms of disease. However, until recently, there was no genetic evidence
      linking dysfunction of tau protein to neurodegeneration and dementia. This has
      now changed with the discovery of close to 20 mutations in the tau gene in
      frontotemporal dementia with Parkinsonism linked to chromosome 17. All cases with
      tau mutations examined to date have shown an abundant filamentous tau pathology
      in brain cells. Pathological heterogeneity is determined to a large extent by the
      location of mutations in tau. Known mutations are either coding region or
      intronic mutations located close to the splice-donor site of the intron
      downstream of exon 10. Most coding region mutations produce a reduced ability of
      tau to interact with microtubules. Several of these mutations also promote
      sulphated glycosaminoglycan-induced assembly of tau into filaments. Intronic
      mutations and some coding region mutations produce increased splicing in of exon
      10, resulting in an overexpression of four-repeat tau isoforms. Thus a normal
      ratio of three-repeat to four-repeat tau isoforms is essential for preventing the
      development of tau pathology. The new work has shown that dysfunction of tau
      protein can cause neurodegeneration and dementia.

PMID- 11447841
TI  - Sites of phosphorylation in tau and factors affecting their regulation.
AB  - The microtubule-associated protein, tau, is the principal component of paired
      helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated
      and a total of 25 sites of phosphorylation have so far been identified. Many of
      these sites are serine or threonine residues that are immediately followed in the
      sequence by proline residues, and hence are candidate phosphorylation sites for
      proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3),
      extracellular signal-related kinase-1 and -2, and mitogen-activated protein
      kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these
      sites, although with different efficiencies for particular sites. Phosphorylation
      studies in transfected cells and neurons show that GSK-3 phosphorylates tau more
      extensively than do these other proline-directed kinases. Mutations in tau have
      been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406-->Trp
      (R406W) tau mutation also affects tau phosphorylation in cells.

PMID- 11447842
TI  - Neurofibrillary tangles and tau phosphorylation.
AB  - Neurofibrillary tangles (NFTs) are a characteristic neuropathological lesion of
      Alzheimer's disease (AD). They are composed of a highly-phosphorylated form of
      the microtubule-associated protein tau. We are investigating the relationship
      between NFTs and microtubule stability and how tau phosphorylation and function
      is affected in transgenic models and by co-expression with beta-amyloid precursor
      protein and presenilins. In most NFT-bearing neurons, we observed a strong
      reduction in acetylated alpha-tubulin immunoreactivity (a marker of stable
      microtubules) and a reduction of the in situ hybridization signal for tubulin
      mRNA. In transfected cells, mutated tau forms (corresponding to tau mutations
      identified in familial forms of frontotemporal dementias linked to chromosome 17)
      were less efficient in their ability to sustain microtubule growth. These
      observations are consistent with the hypothesis that destabilization of the
      microtubule network is an important mechanism of cell dysfunction in Alzheimer's
      disease. The glycogen synthase kinase-3 beta (GSK-3 beta) generates many
      phosphorylated sites on tau. We performed a neuroanatomical study of GSK-3 beta
      distribution showing that developmental evolution of GSK-3 beta
      compartmentalization in neurons paralleled that of phosphorylated tau. Studies on
      transfected cells and on cultured neurons showed that GSK-3 beta activity
      controls tau phosphorylation and tau functional interaction with microtubules.
      Tau phosphorylation was not affected in neurons overexpressing beta-amyloid
      precursor protein. Transgenic mice expressing a human tau isoform and double
      transgenic animals for tau and mutated presenilin 1 have been generated; a
      somatodendritic accumulation of phosphorylated transgenic tau proteins, as
      observed in the pretangle stage in AD, has been observed but NFTs were not found,
      suggesting that additional factors might be necessary to induce their formation.

PMID- 11447843
TI  - Presenilin function: connections to Alzheimer's disease and signal transduction.
AB  - Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are associated
      with early-onset familial Alzheimer's disease which displays an accelerated
      deposition of amyloid plaques and neurofibrillary tangles. Presenilins are multi
      spanning transmembrane proteins which localize primarily to the endoplasmic
      reticulum and the Golgi compartments. We have previously demonstrated that PS1
      exists as a high-molecular-mass complex that is likely to contain several
      functional ligands. Potential binding proteins were screened by the yeast two
      hybrid system using the cytoplasmically orientated PS1 loop domain which was
      shown to interact strongly with members of the armadillo family of proteins,
      including beta-catenin, p0071 and a novel neuron-specific plakophilin-related
      armadillo protein (NPRAP). Armadillo proteins can have dual functions that
      encompass the stabilization of cellular junctions/synapses and the mediation of
      signal transduction pathways. Our observations suggest that PS1 may contribute to
      both aspects of armadillo-related pathways involving neurite outgrowth and
      nuclear translocation of beta-catenin upon activation of the wingless (Wnt)
      pathway. Alzheimer's disease (AD)-related presenilin mutations exhibit a dominant
      gain of aberrant function resulting in the prevention of beta-catenin
      translocation following Wnt signalling. These findings indicate a functional role
      for PS1 in signalling and suggest that mistrafficking of selected presenilin
      ligands may be a potential mechanism in the genesis of AD.

PMID- 11447844
TI  - The God game no more. The feds crack down on a human cloning lab.

PMID- 11447845
TI  - Inner space: the spinal frontier.

PMID- 11447846
TI  - The scientist who saw what we're made of.

PMID- 11447847
TI  - Ground water is alive and well--it just keeps shifting.

PMID- 11447848
TI  - Trace metal concentrations in shallow ground water.
AB  - Trace metal clean sampling and analysis techniques were used to examine the
      temporal patterns of Hg, Cu, and Zn concentrations in shallow ground water, and
      the relationships between metal concentrations in ground water and in a
      hydrologically connected river. Hg, Cu, and Zn concentrations in ground water
      ranged from 0.07 to 4.6 ng L-1, 0.07 to 3.10 micrograms L-1, and 0.17 to 2.18
      micrograms L-1, respectively. There was no apparent seasonal pattern in any of
      the metal concentrations. Filtrable Hg, Cu, and Zn concentrations in the North
      Branch of the Milwaukee River ranged from below the detection limit to 2.65 ng Hg
      L-1, 0.51 to 4.30 micrograms Cu L-1, and 0.34 to 2.33 micrograms Zn L-1. Thus,
      metal concentrations in ground water were sufficiently high to account for a
      substantial fraction of the filtrable trace metal concentration in the river.
      Metal concentrations in the soil ranged from 8 to 86 ng Hg g-1, 10 to 39
      micrograms Cu g-1, and 15 to 84 micrograms Zn g-1. Distribution coefficients, KD,
      in the aquifer were 7900, 22,000, and 23,000 L kg-1 for Hg, Cu, and Zn,
      respectively. These values were three to 40 times smaller than KD values observed
      in the Milwaukee River for suspended particulate matter.

PMID- 11447849
TI  - Hydrogeological research: beginning of the end or end of the beginning?
AB  - This paper uses citation data to assess whether articles published in key ground
      water journals such as Ground Water (GW) and Water Resources Research (WRR) are
      impacting research. Citation information was obtained from SCI Journal Citation
      Reports and The Web of Science--databases maintained by the Institute for
      Scientific Information (ISI). Information extracted from The Web of Science was
      processed further to remove corrections to papers, discussion/replies, and book
      reviews. Generally, there are many ground water papers published, but citations
      of these papers are limited. Approximately 10% to 15% of WRR articles, and 2% to
      3% of GW articles attract more than 50 citations in their lifetimes. In both GW
      and WRR, the top 10% of papers eventually will contribute nearly half of the
      total yearly citations. Another emerging trend is a diminishing emphasis on
      citations to new work as compared to work more than 10 years in age. When
      articles in Ground Water or Journal of Hydrology cite papers in Water Resources
      Research, those papers cite work 10 or more years old half of the time. If one
      believes that citations are a measure of science impact, then there is cause for
      concern. Research is inefficient with much produced for little gain. On a typical
      industrial life-cycle curve, ground water research is likely ranked as mature and
      close to aging. At this stage, much work will have been completed and the number
      of truly impactful problems will have dwindled to just a few.

PMID- 11447850
TI  - Exercises illustrating flow in porous media.
AB  - A set of physically based exercises is described for illustrating concepts and
      processes related to fluid movement in porous media. These exercises revolve
      around a permeameter that costs several dollars to construct and requires no
      external equipment and no electrical power to operate. The exercises can be used
      to illustrate concepts related to pressure and fluid statics, Darcy's equation
      for both gases and liquids, infiltration, and flow in layered media. Although the
      permeameter was originally developed as a teaching aid, it may also be useful in
      field applications as a tool to estimate air and hydraulic conductivity.
      Additional testing is recommended to further assess the accuracy of the results
      for field applications.

PMID- 11447851
TI  - The steady-state dipole-flow test for characterization of hydraulic conductivity
      statistics in a highly permeable aquifer: Horkheimer Insel site, Germany.
AB  - Over the last decade the dipole-flow test (DFT) evolved from the general idea of
      using recirculatory flow to evaluate aquifer properties, to the development of
      prototype instrumentation and feasibility studies, to a reliable tool for
      characterization of aquifer heterogeneity. The DFT involves the interpretation of
      head in recirculatory flow between injection and extraction sections (chambers)
      in a single well isolated from each other by a multipacker system. In this study,
      the steady-state dipole flow test (DFT) has been used to characterize the
      statistics of horizontal hydraulic conductivity (Kr) of the highly permeable,
      heterogeneous, and thin aquifer at the Horkheimer Insel site, Germany. In
      previous studies, Kr estimates were based on the steady-state head difference
      between chambers. A new by-chamber interpretation is proposed that is based on
      drawdown within each individual chamber. This interpretation yields more detailed
      information on structure of heterogeneity of the aquifer without introducing
      complexity into the analysis. The DFT results indicate that Kr ranges from 49 to
      6000 m/day (mean ln Kr [(m/s)] approximately -4, and variance of ln Kr [(m/s)]
      approximately 1-2). Descriptive statistics from the DFT compare well with those
      from previous field and laboratory tests (pumping, borehole flowmeter, and
      permeameter tests and grain-size analysis) at this site. It is shown that the
      role of confining boundaries in the DFT interpretation is negligible even in this
      case of a thin (< 4 m thick) aquifer. This study demonstrates the flexibility of
      the DFT and expands the potential application of this method to a wide range of
      hydrogeologic settings.

PMID- 11447852
TI  - Effect of natural gas exsolution on specific storage in a confined aquifer
      undergoing water level decline.
AB  - The specific storage of a porous medium, a function of the compressibility of the
      aquifer material and the fluid within it, is essentially constant under normal
      hydrologic conditions. Gases dissolved in ground water can increase the effective
      specific storage of a confined aquifer, however, during water level declines.
      This causes a reduction in pore pressure that lowers the gas solubility and
      results in exsolution. The exsolved gas then displaces water from storage, and
      the specific storage increases because gas compressibility is typically much
      greater than that of water or aquifer material. This work describes the effective
      specific storage of a confined aquifer exsolving dissolved gas as a function of
      hydraulic head and the dimensionless Henry's law constant for the gas. This
      relation is applied in a transient simulation of ground water discharge from a
      confined aquifer system to a collapsed salt mine in the Genesee Valley in western
      New York. Results indicate that exsolution of gas significantly increased the
      effective specific storage in the aquifer system, thereby decreasing the water
      level drawdown.

PMID- 11447853
TI  - Ground water/surface water interactions in Lake Naivasha, Kenya, using delta 18O,
      delta D, and 3H/3He age-dating.
AB  - We have analyzed a series of ground water samples from the Lake Naivasha region,
      Kenya, for their helium isotopic composition. Lake Naivasha is unique among the
      East Africa Rift Valley lakes in that it is fresh. It has long been thought that
      the low salinity of this lake is due, in part, to rapid water loss from the lake
      into the local ground water system. Our results show that the Olkaria geothermal
      waters, south of the lake, are devoid of tritium and, thus, are more than 50
      years old. An important implication of these results is that even if Olkaria
      geothermal reservoir water originated from Lake Naivasha, it has been underground
      for a long time, (> 50 years) and is not derived from present-day Lake Naivasha
      water. This flow time is of the same order of magnitude as conservative major
      solutes, such as chloride, as determined through residence time calculations. On
      the north side of Lake Naivasha, deep wells (91 m) have water approximately 20
      years old. Water from these wells has stable isotopic values resembling those of
      nearby rivers, and high-elevation eastern Rift water. This indicates that this
      water recharges from rains from high eastern Rift Valley escarpments. Many of the
      shallow wells on the south side of the lake have 3H/3He ages between four and 17
      years. The young ages and the delta 18 O-enriched signature of the water from
      these wells indicate that they are recharged by a mixture of water from the lake,
      Rift flanks, and water from deep pumping wells that is recharged during
      irrigation. Water mixing ratio calculations using delta 18O and delta D isotopes
      show that about 50% to 70% of the southern ground water system is derived from
      the lake, while the Olkaria geothermal reservoir water shows that 40% to 50% of
      this water is originally lake water. Calculated mean recharge rates range from
      0.10 to 1.59 m/yr with a mean of 0.52 +/- 0.40 m/yr. Estimated horizontal
      velocity from 3H/3He age dating between Lake Naivasha and a well about 3 km to
      the south is 75 m/yr, giving average horizontal hydraulic conductivity of 6
      m/day.

PMID- 11447854
TI  - Numerical simulation of a natural gradient tracer experiment for the natural
      attenuation study: flow and physical transport.
AB  - Results are presented for numerical simulations of ground water flow and physical
      transport associated with a natural gradient tracer experiment conducted within a
      heterogeneous alluvial aquifer of the Natural Attenuation Study (NATS) site near
      Columbus, Mississippi. A principal goal of NATS is to evaluate biogeochemical
      models that predict the rate and extent of natural biodegradation under field
      conditions. This paper describes the initial phase in the model evaluation
      process, i.e., calibration of flow and physical transport models that simulate
      conservative bromide tracer plume evolution during NATS. An initial large-scale
      flow model (LSM) is developed encompassing the experimental site and surrounding
      region. This model is subsequently scaled down in telescopic fashion to an
      intermediate-scale ground water flow model (ISM) covering the tracer-monitoring
      network, followed by a small-scale transport model (SSM) focused on the small
      region of hydrocarbon plume migration observed during NATS. The LSM uses inferred
      depositional features of the site in conjunction with hydraulic conductivity (K)
      data from aquifer tests and borehole flowmeter tests to establish large-scale K
      and flow field trends in and around the experimental site. The subsequent ISM
      incorporates specified flux boundary conditions and large-scale K trends obtained
      from the calibrated LSM, while preserving small-scale K structure based on some
      4000 flowmeter data for solute transport modeling. The configuration of the ISM
      predicted potentiometric surface approximates that of the observed surface within
      a root mean squared error of 0.15 m. The SSM is based on the dual-domain mass
      transfer approach. Despite the well-recognized difficulties in modeling solute
      transport in extremely heterogeneous media as found at the NATS site, the dual
      domain model adequately reproduced the observed bromide concentration
      distributions. Differences in observed and predicted bromide concentration
      distributions are attributed to aquifer heterogeneity at the decimeter (dm) and
      smaller scales. The calibrated transport parameters for the SSM (i.e., 1:7 for
      the ratio of mobile-to-total porosity; 2.5 x 10(-3) day-1 for the mass-transfer
      coefficient; 1 m for longitudinal dispersivity; and 0.1 m for transverse
      dispersivity) are consistent with separate numerical simulations of two earlier
      tracer experiments at the site. The multiscale modeling approach adopted in this
      study permits the incorporation of both large-scale geologic features important
      for flow simulation and small-scale heterogeneities critical for transport
      simulation. In addition, the dual-domain transport model provides a foundation
      for multispecies reactive transport modeling studies of natural attenuation of
      hydrocarbons during NATS.

PMID- 11447855
TI  - Riverbed permeabilities: information from pooled data.
AB  - Numerical values of hydraulic conductivities of river channel-lining materials
      are assembled from published and unpublished sources. These are found to cover a
      range from below 1.0 x 10(-9) to above 1.0 x 10(-2) m sec-1 and to be
      concentrated in the region 1.0 x 10(-7) to 1.0 x 10(-3) m sec-1. Variability
      within a site can be large. Assessment of the values in relation to sediment,
      scale, and method of determination presents a complex picture, and generalization
      is not straightforward. Hydraulic conductivity determinations from numerical
      modeling, which tends to be associated with averaging at larger spatial scales,
      are associated with a more conservative range of values than those derived from
      field and laboratory analyses. The sample of determinations provides a guideline
      basis of representative values for hydrological and hydrogeological assessment
      where specific investigation is not possible.

PMID- 11447856
TI  - A joint TEM-HLEM geophysical approach to borehole sitting in deeply weathered
      granitic terrains.
AB  - The accurate location of aquiferous fracture zones in granite beneath a > 50 m
      thick weathered mantle in semi-arid regions is a major hydrogeological problem.
      It is expected that the zone of intensive fracturing will be more susceptible to
      weathering and thus be characterized by the thickest development of saprolite, a
      good electrically conductive target for deep-probing electromagnetic systems. The
      single-loop transient electromagnetic (TEM) technique is well known to have the
      capability for detecting concealed steep mineralized targets in mining
      environments and can be adapted to this hydrogeological problem. We propose that
      combining the conventional frequency-domain horizontal-loop electromagnetic
      (HLEM) and single-loop TEM is an effective practical approach to locating
      concealed aquiferous fracture zones. In the supporting case studies presented
      here, we deployed multifrequency HLEM profiling (with 50 m transmitter-receiver
      separation) and TEM soundings with contiguous 10 or 20 m sided loops along the
      survey lines in a granitic terrain affected by deep (> 50 m) weathering in
      northeast Brazil. A somewhat layered structure consisting of resistive
      hardpan/leached zone, conductive saprolite, and resistive basement is
      identifiable in the typical TEM depth sounding data. We obtained coincident HLEM
      and TEM anomalies at all the sites, enabling a relatively straightforward
      selection of potential drilling positions. Simple resistivity-depth
      transformation of the TEM data was done for each site, yielding an approximate
      section from which drilling depths were estimated. All of the boreholes located
      were successful. Although our results appear to indicate that the single-loop TEM
      method could be used independently for borehole sitting in deeply weathered
      granitic terrains and that the weathering profile over granite can be mapped
      using TEM depth soundings of appropriate observational bandwidth, we recommend a
      joint electromagnetic approach for optimal well sitting.

PMID- 11447857
TI  - Exploitation of high-yields in hard-rock aquifers: downscaling methodology
      combining GIS and multicriteria analysis to delineate field prospecting zones.
AB  - Based on research work in the Truyere River catchment of the Massif Central
      (Lozere Department, France), a methodology has been developed for delineating
      favorable prospecting zones of a few square kilometers within basement areas of
      several hundred, if not thousand, square kilometers for the purpose of sitting
      high-yield water wells. The methodology adopts a functional approach to hard-rock
      aquifers using a conceptual model of the aquifer structure and of the functioning
      of the main aquifer compartments: the alterites (weathered and decayed rock), the
      underlying weathered-fissured zone, and the fractured bedrock. It involves an
      economically feasible method of mapping the thickness and spatial distribution of
      the alterites and the weathered-fissured zone, on which the long-term
      exploitation of the water resource chiefly depends. This method is used for the
      first time in hydrogeology. The potential ground water resources were mapped by
      GIS multicriteria analysis using parameters characterizing the structure and
      functioning of the aquifer, i.e., lithology and hydrogeological properties of the
      substratum, nature and thickness of the alterites and weathered-fissured zone,
      depth of the water table, slope, fracture networks and present-day tectonic
      stresses, and forecasted ground water quality. The methodology involves a
      coherent process of downscaling that, through applying methods that are
      increasingly precise but also increasingly costly, enables the selection of sites
      with diminishing surface areas as the work advances. The resulting documents are
      used for ground water exploration, although they can also be applied to the
      broader domain of land-use management.

PMID- 11447858
TI  - A numerical model and spreadsheet interface for pumping test analysis.
AB  - Curve-matching techniques have been the standard method of aquifer test analysis
      for several decades. A variety of techniques provide the capability of evaluating
      test data from confined, unconfined, leaky aquitard, and other conditions. Each
      technique, however, is accompanied by a set of assumptions, and evaluation of a
      combination of conditions can be complicated or impossible due to intractable
      mathematics or nonuniqueness of the solution. Numerical modeling of pumping tests
      provides two major advantages: (1) the user can choose which properties to
      calibrate and what assumptions to make; and (2) in the calibration process the
      user is gaining insights into the conceptual model of the flow system and
      uncertainties in the analysis. Routine numerical modeling of pumping tests is now
      practical due to computer hardware and software advances of the last decade. The
      RADFLOW model and spreadsheet interface presented in this paper is an easy-to-use
      numerical model for estimation of aquifer properties from pumping test data.
      Layered conceptual models and their properties are evaluated in a trial-and-error
      estimation procedure. The RADFLOW model can treat most combinations of confined,
      unconfined, leaky aquitard, partial penetration, and borehole storage conditions.
      RADFLOW is especially useful in stratified aquifer systems with no identifiable
      lateral boundaries. It has been verified to several analytical solutions and has
      been applied in the Snake River Plain Aquifer to develop and test conceptual
      models and provide estimates of aquifer properties. Because the model assumes
      axially symmetrical flow, it is limited to representing multiple aquifer layers
      that are laterally continuous.

PMID- 11447859
TI  - Application of continuous time random walk theory to tracer test measurements in
      fractured and heterogeneous porous media.
AB  - We examine a set of analytical solutions based on the continuous time random walk
      (CTRW) approach, which can be evaluated numerically and used to analyze
      breakthrough data from tracer tests. Practical application of these solutions,
      with discussion of the physical meaning of the relevant model parameters, is
      emphasized. The CTRW theory accounts for the often observed non-Fickian (or scale
      dependent) dispersion behavior that cannot be properly quantified by using the
      advection-dispersion equation. The solutions given here, valid for a wide range
      of dispersive behaviors of conservative tracers, and useful for both
      characterization and prediction, have been integrated into a library of external
      functions for use with the GRACE graphical display and analysis package. Example
      applications of these solutions are presented. The library and graphics software
      are freely accessible from a Web site.

PMID- 11447860
TI  - Introduction of wavelet analyses to rainfall/runoffs relationship for a karstic
      basin: the case of Licq-Atherey karstic system (France).
AB  - Karstic systems are highly heterogeneous geological formations characterized by a
      multiscale temporal and spatial hydrologic behavior with more or less localized
      temporal and spatial structures. Classical correlation and spectral analyses
      cannot take into account these properties. Therefore, it is proposed to introduce
      a new kind of transformation: the wavelet transform. Here we focus particularly
      on the use of wavelets to study temporal behavior of local precipitation and
      watershed runoffs from a part of the karstic system. In the first part of the
      paper, a brief mathematical overview of the continuous Morlet wavelet transform
      and of the multiresolution analysis is presented. An analogy with spectral
      analyses allows the introduction of concepts such as wavelet spectrum and cross
      spectrum. In the second part, classical methods (spectral and correlation
      analyses) and wavelet transforms are applied and compared for daily rainfall
      rates and runoffs measured on a French karstic watershed (Pyrenees) over a period
      of 30 years. Different characteristic time scales of the rainfall and runoff
      processes are determined. These time scales are typically on the order of a few
      days for floods, but they also include significant half-year and one-year
      components and multi-annual components. The multiresolution cross-analysis also
      provides a new interpretation of the impulse response of the system. To conclude,
      wavelet transforms provide a valuable amount of information, which may be now
      taken into account in both temporal and spatially distributed karst modeling of
      precipitation and runoff.

PMID- 11447861
TI  - Evaluation of recharge in a small temperate catchment using natural and applied
      delta 18O profiles in the unsaturated zone.
AB  - A water balance study was used for determining recharge rate and mechanisms in
      the Enler Catchment, Northern Ireland. Here spatially limited data for the water
      balance resulted in varied calculation of the annual and monthly net infiltration
      rate. This paper outlines a method whereby high-resolution soil profiles (1 to 2
      cm) were obtained from field cores in the upper 2 m of the unsaturated zone using
      delta 18O of water. These profiles show changes in isotopic composition that
      range from individual rainfall events to annually integrated cycles of rainfall.
      Recharge rates were calculated from stable isotope profiles for each of the four
      main soil types in the study catchment and summed over each area resulting in an
      average recharge in the range 55 to 70 mm/a, which is comparable with previous
      findings. Applied isotopic tracer tests were also conducted to evaluate the
      extent of preferential flow through the two main soil types in the catchment.
      Rates of water movement found from these experiments show good agreement with
      natural isotopic profiles; however, evidence suggests that preferential flow is
      not the dominant process controlling water movement in this catchment. This type
      of data provides valuable information about recharge rates and mechanisms and may
      facilitate better prediction of contaminant transport pathways in the vadose
      zone.

PMID- 11447862
TI  - Calibration of the DRASTIC ground water vulnerability mapping method.
AB  - Ground water vulnerability maps developed using the DRASTIC method have been
      produced in many parts of the world. Comparisons of those maps with actual ground
      water quality data have shown that the DRASTIC method is typically a poor
      predictor of ground water contamination. This study significantly improved the
      effectiveness of a modified DRASTIC ground water vulnerability map by calibrating
      the point rating schemes to actual ground water quality data by using
      nonparametric statistical techniques and a geographic information system.
      Calibration was performed by comparing data on nitrite plus nitrate as nitrogen
      (NO2 + NO3-N) concentrations in ground water to land-use, soils, and depth to
      first-encountered ground water data. These comparisons showed clear statistical
      differences between NO2 + NO3-N concentrations and the various categories. Ground
      water probability point ratings for NO2 + NO3-N contamination were developed from
      the results of these comparisons, and a probability map was produced. This ground
      water probability map was then correlated with an independent set of NO2 + NO3-N
      data to demonstrate its effectiveness in predicting elevated NO2 + NO3-N
      concentrations in ground water. This correlation demonstrated that the
      probability map was effective, but a vulnerability map produced with the
      uncalibrated DRASTIC method in the same area and using the same data layers was
      not effective. Considerable time and expense have been out-laid to develop ground
      water vulnerability maps with the DRASTIC method. This study demonstrates a cost
      effective method to improve and verify the effectiveness of ground water
      vulnerability maps.

PMID- 11447863
TI  - Comparison of continuous and cyclic pumping from a well.
AB  - Two practically applicable pumping patterns for wells are: (1) continuous pumping
      at a sustainable constant rate; and (2) pumping at a sustainable constant rate
      for a fixed period every day (cyclic pumping). Theoretical analysis shows that
      with the cyclic pumping pattern the pump can be run at a higher rate than with
      continuous pumping. However continuous pumping at the maximum continuously
      sustainable constant rate produces considerably more water. If the objective is
      to produce as much water as possible, it is important to use a pump designed for
      running at the maximum continuously sustainable rate.

PMID- 11447864
TI  - Generating change. Health Devices motivates suppliers to improve their products.

PMID- 11447865
TI  - Minimizing hazardous exposures in the healthcare environment.
AB  - Consider the following scenarios: A central processing employee suffers eye and
      respiratory irritation from exposure to a glutaraldehyde solution while cleaning
      an endoscope. Biomedical engineering personnel contact blood and other body
      fluids while repairing contaminated dialysis units. A food service employee
      contracts TB while serving meals within a TB-isolation ward. These are all
      examples of exposures to hazards in a hospital. What do they have in common? They
      could have easily been prevented. Hazards exist almost everywhere in a hospital.
      In a typical workday, a healthcare worker (HCW) may circulate to many different
      hospital locations, encountering numerous hazards--some familiar and some not.
      Thus, it's important that every HCW is aware of potential exposures, has access
      to relevant information, and is trained on protective equipment so that the risk
      of an adverse exposure may be greatly reduced. This article is directed toward
      the hospital employee. While not an all-inclusive, step-by-step guide to the
      hazards found within a particular department, this article is meant to raise
      awareness. It contains basic information on hazards, the consequences of
      exposure, and ways in which HCWs can protect themselves as well as patients and
      visitors. This information is presented to help educate both new and existing
      staff and to prevent unnecessary exposures.

PMID- 11447866
TI  - OSHA's hazard communication standard. What it means for U.S. hospitals.
AB  - Chemical hazards are an important issue for employers, employees, and the
      organizations that represent them. In the United States, this fact is reflected
      in the proliferation of state and federal laws designed to provide workers with
      the means to protect themselves from such hazards. "Right-to-know" legislation,
      as these laws have become known, are intended to help employees learn about
      potential chemical hazards in the workplace and how to avoid them. In this
      article, we focus on the federal right-to-know law--the U.S. Occupational Safety
      and Health Administration's hazard communication standard--discussing in general
      terms the tasks that U.S. hospitals must perform to comply with the standard.
      We've simplified these tasks into (1) identifying hazardous agents, (2)
      developing and implementing a written hazard communication program, and (3)
      training employees.

PMID- 11447867
TI  - External biphasic defibrillators. Should you catch the wave?
AB  - Introduced about five years ago, external biphasic defibrillators have attracted
      a lot of attention. The biphasic waveforms they use have been shown in some
      studies to be more successful than standard monophasic waveforms in terminating
      ventricular fibrillation and ventricular tachycardia. But with this apparent step
      forward comes confusion: A variety of biphasic waveforms are available, and each
      defibrillator supplier is making claims for the superiority of its particular
      waveform. Are biphasic waveforms really better than monophasic? Is any one
      biphasic waveform preferable to another? What does the clinical literature say
      about this technology? This article answers those and other pressing questions
      about biphasic defibrillators.

PMID- 11447868
TI  - Hazard report. Unnoticed pulse oximeter sensor disconnections on certain GE
      medical Systems Information Technologies monitors.

PMID- 11447869
TI  - Hazard report. Don't store service materials in electrical cabinets.

PMID- 11447871
TI  - Talk to the specialist. Longevity of x-ray tubes in multislice CT scanners.

PMID- 11447870
TI  - User experience network. Aircast VenaFlow System compression units may have high
      ground resistances.

PMID- 11447872
TI  - [Atrial fibrillations: daily occurrence possibly leading to embolism in an
      extremity].
AB  - A 64-year old woman had been tired and short of breath for the previous few
      months. During the past few days she had experienced disruptions in the movement
      and feeling of the right arm and both feet as well as a loss of strength and a
      heavy feeling in her right leg. Due to atrial fibrillation she had recently
      started using digoxin and due to possible arterial embolisms in the extremities
      she had recently started using acenocoumarol. Further investigations revealed one
      large thrombus in the left atrium, two large thrombi in the left auricle and a
      serious constriction in the right iliac artery. The thrombi were treated with
      heparin and oral anticoagulants; the ischaemia which probably occurred as a
      result of this was successfully treated with embolectomy. After the cardiac
      thrombi had disappeared, the patient was electrically converted to sinus rhythm.
      One month later, the patient was still in sinus rhythm and her clinical picture
      had improved. As she does not feel the atrial fibrillation, she will be
      permanently maintained on oral anticoagulants. In patients with atrial
      fibrillations, the possibility of an embolisation towards the extremities
      deserves serious consideration.

PMID- 11447873
TI  - [Antibiotic resistance: recommendations from the Advisory Council for Health
      Research].
AB  - The Advisory Council for Health Research (RGO) advised the Dutch Minister of
      Health on research into the epidemiology, prevention and research of antibiotic
      resistance in the Netherlands. Good antimicrobial practice, insight into
      antibiotic use, implementation of measures to prevent development of resistance
      and fundamental research on resistance should be promoted. It was concluded that
      there is very little extramural surveillance and that only a few existing
      intramural surveillance programmes appear useful for long-term monitoring,
      inclusion into international databases and comparison purposes. The initiatives
      taken by the Working Party on Antibiotic Policy (SWAB) and the National Institute
      of Public Health and the Environment (RIVM), including the development of a
      standard for susceptibility testing and the coordination of surveillance studies
      according to international standards, should be supported and continued. The RGO
      committee is impressed by central and integrated national surveillance programmes
      such as those in Denmark or Finland. This approach however seems not necessary
      for good medical practice and not currently feasible. Priority should now be
      given to specific projects which focus on specific resistance problems among well
      defined patient groups, and on indicator-organisms and indicator-antibiotics.

PMID- 11447874
TI  - [Treatment of metastatic testicular carcinoma according to prognosis; new
      development].
AB  - The majority of patients with a metastatic germ cell tumour can be successfully
      treated with a combination chemotherapy containing cisplatin. For more than a
      decade the combination of cisplatin, etoposide and bleomycin (BEP) has been the
      gold standard of treatment. In both the United States and Europe, a number of
      studies have been carried out, with the purpose of reducing the toxicity of the
      treatment for patients with a good prognosis as well as improving the treatment
      result for patients with intermediate or unfavourable prognostic characteristics,
      by intensifying the chemotherapy regimen or by adding new cytotoxic agents. The
      standard treatment for patients with a good prognosis consists at present of
      three BEP cycles, which can be administered in a shortened schedule of three days
      per cycle. Bleomycin is essential for the success of the therapy and cisplatin
      cannot be replaced by carboplatin. Efforts to increase the dose of cisplatin per
      cycle, reduce the interval between cycles, the addition of ifosfamide and
      sequential/alternating therapy do not provide any additional benefit compared to
      the standard treatment with BEP.

PMID- 11447875
TI  - [Drug-induced heart failure].
AB  - Although heart failure is predominantly caused by cardiovascular disorders,
      several classes of drugs may induce heart failure in patients with pre-existing
      normal left ventricular function or may precipitate the occurrence of heart
      failure in patients with left ventricular impairment. These drugs are
      predominantly those belonging to the categories of cytostatics, anti-arrhythmics,
      beta-blockers, nonsteroidal anti-inflammatory drugs, calcium channel blockers and
      anaesthetics. Drug-induced heart failure should be regarded as a potentially
      preventable cause of heart failure, although sometimes therapeutic alternatives
      are scarce (e.g. anthracycline-induced cardiomyopathy). Awareness of the
      possibility of adverse effects on cardiac performance by several classes of
      drugs, particularly in patients with pre-existing ventricular impairment, may
      contribute to prevention or timely diagnosis and treatment of drug-induced heart
      failure.

PMID- 11447876
TI  - [Diagnostic image (43). Carcinoid of mesentery of small intestine and hepatic
      metastases].
AB  - A 49-year-old woman who suffered from vomiting and diarrhea was diagnosed with a
      carcinoid in the mesentery of the small bowel and metastases in the liver.

PMID- 11447877
TI  - [Laparoscopic myotomy in 14 patients with achalasia after unsuccessful pneumatic
      dilatations: effective and safe].
AB  - OBJECTIVE: Evaluation of laparoscopic myotomy with or without an anti-reflux
      (Dor) procedure in patients with achalasia. DESIGN: Retrospective. METHOD: Data
      were collected from patients who underwent a laparoscopic myotomy for achalasia,
      following repeated pneumatic dilations. In the period 1993-1998, seven patients
      were treated in the Dijkzigt location of the Erasmus University Hospital
      (Rotterdam, the Netherlands). In the period 1995-1999 seven patients were treated
      in the Free University Hospital (Amsterdam, the Netherlands) by means of a
      laparoscopic myotomy followed by Dor fundoplication. All of the patients received
      a check-up from their specialist according to a protocol and in 2000 they were
      requested to complete a questionnaire concerning how satisfied they were with the
      operation. RESULTS: In both groups the age ranged from 20 to 60 years (mean ages
      were 39 and 36 respectively) and the number of men and women was almost equal.
      There was no conversion. Average operation time was 1.5 hours for the group
      without fundoplication and 2.5 hours for the group with fundoplication. No
      perioperative or postoperative complications occurred. During the follow-up
      period (mean: 3.5 years; range: 1-7) one recurrence was encountered. In the group
      without fundoplication, reflux oesophagitis was observed in five of the patients.
      No reflux was encountered in the group with the added fundoplication. All of the
      patients preferred laparoscopic myotomy to pneumatic dilations. CONCLUSION:
      Laparoscopic myotomy was an effective and safe treatment for achalasia following
      repeated pneumatic dilations. The patients themselves were also satisfied.
      Without fundoplication, reflux oesophagitis was more prevalent.

PMID- 11447878
TI  - [Treatment of intra-atrial reentry tachycardia by catheter ablation, using three
      dimensional electro-anatomical map of the atrial activation pattern].
AB  - A 30-year-old man, who had been treated surgically for tricuspid valve atresia as
      a boy, suffered from recurrent supraventricular tachycardias. These atrial
      reentry tachycardias are frequent post-operative complications in patients with
      congenital heart disease. The reentry circuit in these patients often circulates
      around areas of scar tissue or surgically created barriers such as incision scars
      and implanted synthetic material. A possible curative treatment of these
      arrhythmias is radiofrequency catheter ablation, which is aimed at interrupting
      critical conduction pathways in the reentry circuit. Accurate location of the
      reentry circuit is, however, mandatory. A new technique, which correlates
      intracardiac signals with specific sites in the endocardium, so-called 'electro
      anatomical mapping', allows accurate three-dimensional location and visualization
      of the borders of the reentry circuit and facilitates catheter ablation of these
      complex reentrant arrhythmias. In this patient, the ablation procedure resulted
      in the disappearance of the rhythm disturbances.

PMID- 11447879
TI  - [Protocols for the treatment of supraventricular tachycardias in the fetus].
AB  - The protocols mentioned are used by Utrecht University Hospital for the treatment
      of foetal supraventricular tachycardias. In the case of atrial flutters the
      pregnant woman is treated with sotalol administered orally and, if no sinus
      rhythm is obtained nor a reduced ventricular rhythm occurs, subsequently with
      digoxin. If there is no hydrops foetalis then this is also the treatment regimen
      for other forms of foetal supraventricular tachycardia. In the case of hydrops
      foetalis the treatment is more aggressive: digoxin intravenously or flecanide
      orally; if the rhythm does not convert into a sinus rhythm nor a reduced
      ventricular rhythm occurs then both of these medications are administered; if
      that also proves to be insufficient then direct foetal therapy can be considered.

PMID- 11447880
TI  - [Increasing importance of cytodiagnostics in the Netherlands].

PMID- 11447881
TI  - [From gene to disease; from BRCA1 OR BRCA2 to breast cancer].

PMID- 11447882
TI  - [Guidelines for diagnosis of urinary tract infections: advantages and
      disadvantages of various strategies].

PMID- 11447883
TI  - Group's capitation mindset spawns three decades of success.

PMID- 11447884
TI  - Successful physician groups are 'sleeping with the enemy'.
AB  - Successful physician groups are "sleeping with the enemy." Groups that consider
      health plans as their partners rather than their opponents have a much better
      chance of success in the risk contracting game.

PMID- 11447885
TI  - Boost capitation profits by making contract negotiations an ongoing process.
AB  - When do you plan for risk contract negotiations? This expert says you should be
      working on your negotiating agenda every day.

PMID- 11447886
TI  - Applying these sound business tenets to capitation management keeps your bottom
      line healthy.
AB  - One consultant who's seen it all says most failed IPAs went under because they
      accepted capitation rates they knew would not cover their costs in the
      expectation that they could live on cash flow or make up the shortfall from
      withholds, hospital surpluses, or drug surpluses. Here's how to avoid the same
      mistakes.

PMID- 11447887
TI  - A new form of capitation will occupy important place in future healthcare
      landscape.

PMID- 11447888
TI  - California small employers feeling pinch of premium increases.

PMID- 11447889
TI  - Medicaid plan rewards positive physician behavior.
AB  - Medicaid HMO L.A. Care offers positive reinforcement in the form of financial
      incentives when physicians do things right and fast.

PMID- 11447891
TI  - Trap design means savings.

PMID- 11447890
TI  - Reviewing efficacy of alternative water treatment techniques.
AB  - This section is designed to provide a brief summary of some of the findings. A
      good deal of work has been conducted by Mr N. L. Pavey and the team at BSRIA,
      Bracknell. The BSRIA publications are an excellent source of further information.
      Ultraviolet radiation: UV radiation of wavelength 254 nm destroys bacteria by a
      mechanism of damaging nucleic acids by producing thymine dimers which disrupt DNA
      replication [Gavdy and Gavdy, 1980]. L. pneumophila has been reported as
      sensitive to UV dosages of 2,500-7,000 uW.s/cm2 [Antopol & Ellner, 1979; Knudson,
      1985]. Antopol and Ellner [1979] examined the susceptibility of L. pneumophila to
      UV dosage. Their results indicated that 50% of the organisms were killed by 380
      uWs/cm2 and 90% were killed by 920 uWs/cm2. Kills of 99 and 99.9% were obtained
      using 1,840 and 2,760 uWs/cm2 respectively. Muraca et al [1987] showed that
      continuous UV irradiation resulted in a 5 logarithm decrease in waterborne L.
      pneumophila in a circulating system. Gilpin [1984] reported that in laboratory
      buffer solutions, exposure to 1 uW of UV radiation per cm2 achieved a 50% kill of
      L longbeachae in 5 minutes, L. gormanii in 2-30 minutes and L pneumophila in 17
      minutes. Exposure times for 99% kills for L. longbeachae, L pneumophila and L.
      Gormanii were 33, 48 and 63 minutes respectively. The same research worker
      conducted experiments using a 3 litre circulating water system, connected to a
      stainless steel housing containing a UV source. The UV lamp output was 7 ergs/mm2
      per second per 100 cm at 254 nm. L. pneumophila was killed within 15 seconds,
      that is within their first pass through the system. Continuous disinfection with
      UV has the advantages of imparting no taste, odour or harmful chemical by
      products and requires minimal operation and maintenance [Muraca et al 1988].
      Keevil et al [1989] state that UV irradiation fails to clear systems of biofilm
      because of poor penetration into microflocs of the micro-organisms. Copper/silver
      ionisation: A recent study of full scale hot water test rigs incorporating copper
      silver ionisation systems has been reported by Pavey, 1996. Copper and silver
      ions were introduced into the water by electrolysis. One of the principal
      mechanisms of biocidal action of these ions is thought to be cell penetration.
      The positively charged copper ions form electrostatic bonds with negatively
      charged sites on the cell wall. The cell membrane is thus distorted, allowing
      ingress of silver ions which attack the cell by binding at specific sites to DNA,
      RNA, respiratory enzymes and cellular protein, causing catastrophic failure of
      the life support systems of the cell. Silver and copper ion concentrations of 40
      and 400 ug/L respectively were effective against planktonic Legionellae in cold
      water systems and hot water systems containing soft water. In hard water, the
      ionisation was ineffective due to the inability to control silver ion
      concentrations. This was caused by scaling of the electrodes and silver ion
      complexation by the high concentration of dissolved solids. Bosch et al [1993]
      had earlier extended the application of copper-silver disinfection to human
      enteric viruses in water, such as adenovirus, rotavirus, hepatitis A virus, and
      poliovirus. Their work showed that copper and silver ions in the presence of
      reduced levels of free chlorine did not ensure the total elimination of viral
      pathogens from water. In the case of an amoeba, Naegleria fowleria [responsible
      for primary amoebic meningoencephalitis], Cassells et al [1995] have demonstrated
      that a combination of silver and copper ions were ineffective at inactivating the
      amoebae at 80 and 800 ug/L respectively. However addition of 1.0 mg/L free
      chlorine produced a synergistic effect, with superior inactivation relative to
      either chlorine or silver-copper in isolation. A similar synergy was reported by
      Yahya et al [1989] in their study of Staphylococcus sp. and Pseudomonas
      aeruginosa. Yahya et al [1992] also suggested an additive or synergistic effect
      in the inactivation of coliphage MS-2 and poliovirus. Other techniques: There are
      a number of other techniques. We have conducted trials of most of these in the
      control of Legionella sp., but these fall out of the scope of this article, and
      as such less emphasis has been placed on them here. Ozonation: Ozone [O3] is an
      oxidising gas, generated electrically from oxygen [O2]. L. pneumophila can be
      killed at < 1 mg/L of ozone [Edelstien et al 1982]. Muraca et al [1987] found
      that 1-2 mg/L of continuous ozone over a six hour contact time, produced a 5
      logarithm decrease of L. pneumophila. The effectiveness of ozone treatment
      against a range of bacteria and coliphages has been studied Botzenhart et al
      [1993]. E. coli was least resistant to ozone, followed by MS 2-coliphage and PhiX
      174-coliphage, with L. pneumophila and Bacillus subtilis spores being the most
      resistant. (ABSTRACT TRUNCATED)

PMID- 11447892
TI  - Examining maintenance responsibilities.
AB  - This paper has examined the important responsibilities of the two organisations
      involved in the provision of maintenance service for the vital building services
      in many of our highly serviced buildings. The issues raised could be put to
      beneficial use in both clients and maintenance providers. All in all, the clients
      should work closely with their maintenance providers. Engineering services in
      buildings will not perform satisfactorily and efficiently if both parties do not
      work together and understand the maintenance tasks based on a business partnering
      mode. Put forward is the view that the management of the activities involved in
      the operation and maintenance process is a "shared commitment/involvement"
      between the client and the maintenance provider. It is obvious that many factors
      can influence the continued effectiveness of a quality maintenance scheme set up
      by client and provider. Some of these factors are: Change in key personnel
      Updates in technology Amendments to engineering practice Implementation of
      legislative requirements Changes in operation by client or provider Change of use
      of building Passage of time These factors must be fully reviewed by both parties
      from time to time, and necessary actions taken. A cooperative team working
      relationship and improved communication should be fostered by the client and his
      provider for the best management of services maintenance. This arrangement will
      contribute to better building services systems with continuous improvement;
      improved value for clients and higher return for the maintenance provider.

PMID- 11447893
TI  - Delivering customised legionella monitoring services.

PMID- 11447894
TI  - Top Type I recommendations for 2000. "Nutritional assessment" listed for
      hospitals, behavioral health, and home care.

PMID- 11447895
TI  - The ABCs of outcomes measurement.

PMID- 11447896
TI  - Documenting resident education in LTC.

PMID- 11447897
TI  - Evidence helps organizations meet JCAHO leadership.

PMID- 11447898
TI  - [Transbronchial needle aspiration for the diagnosis of mediastinal adenopathy].

PMID- 11447899
TI  - [Clinical usefulness and cost-effectiveness of transbronchial needle aspiration
      for the diagnosis of mediastinal adenopathy].
AB  - Transbronchial needle aspiration (TBNA) of mediastinal or hilar enlarged lymph
      nodes is a useful and safe technique. Nevertheless, its use has not become
      widespread, and the necessity of a specific training to obtain good results has
      been reported. In order to evaluate the clinical usefulness and cost
      effectiveness of TBNA in inexperienced brochoscopists in this technique, a
      prospective study was conducted of this technique used in all patients with a
      chest CT with paratracheobronchial lymph nodes larger than 10 mm who had a
      fiberbronchoscopy ordered. TBNA was performed in 66 lymph node staging in 59
      patients. In 76% of cases adequate specimens were obtaned, and a cytohistologic
      diagnosis was established in 59%. In 44% of patients, TBNA avoided other more
      invasive diagnostic procedures. Had TBNA not been performed, cost was estimated
      to have been at least five times higher. We conclude that TBNA could be a useful
      cost-effective technique in inexperienced teams.

PMID- 11447900
TI  - [Decisions and therapeutic attitudes for patients with white coat hypertension].
AB  - OBJECTIVE: To analyze the different therapeutic attitudes towards patients with
      arterial hypertension (AH) or white coat hypertension (WCH). DESIGN:
      Longitudinal, retrospective study after performing a 24 h ambulatory blood
      pressure monitoring of ABPM. SETTING: Urban health center. PATIENTS: Eighty-six
      patients aged over 15 years, not treated and with figures of a poor blood
      pressure control (> 140 and/or > 90 mmHg), followed for a mean of four years.
      INTERVENTION: Initial 24-h ABPM (SpaceLabs 90202-90207). DETERMINATIONS AND MAIN
      RESULTS: After ABPM 43 patients were classified as having WCH and 43 patients AH.
      Both groups were comparable. Pharmacologic treatment was begun from 41.9% (n =
      18) of WCH and 88.4% (n = 38) of AH (p < 0.001) patients with a delay, after
      ABPM, of 19 months (SD 22) and 1.2 months (SD 3.2), respectively (p < 0.01). At
      the end of the follow-up period patients with AH had more target organs involved.
      CONCLUSIONS: The information provided by ABPM probably entails a more
      conservative approach at the beginning of pharmacologic treatment.

PMID- 11447901
TI  - [Prevalence and characteristics of complications of Baker cysts by MRI].
AB  - OBJECTIVE: To evaluate the prevalence and describe the findings of complicated
      Baker cysts observed in a large series of knee MR studies. MATERIALS AND METHODS:
      A total of 145 Baker cysts were detected out of a series of 382 (38%) consecutive
      patients with knee MR studies performed. Cysts were classified as simple (smooth
      walls, homogeneous content, signal intensity similar to that of the synovial
      fluid and with no changes in the surrounding tissues) or complicated (changes of
      wall, changes in the intensity of the content signal, presence of free bodies or
      changes in the surrounding tissues). Complications were detected in ten (6.9%)
      cysts, which were confirmed by means of direct observation (arthroscopy or
      surgery, n = 9 cases) or by means of clinical evidence with follow-up (n = 1
      case). RESULTS: No differences were detected in sex distribution between simple
      and complicated cysts (chi 2, p = 0.09), although a statistically significant
      relationship was indeed detected between the presence of complications with older
      age (p = 0.003) and presence of meniscal lesions (p = 0.019). In five patients a
      rupture of the Baker cyst was found, in four intracystic free bodies, and in one
      case pigmented villonodular synovitis with intracystic foci. Only two out of the
      five patients with cyst rupture had thrombophlebitis symptoms, the remaining of
      ruptures being asymptomatic. In three out of the four patients with free
      intracystic bodies they were considered secondary to degenerative osteochondral
      lesions, the other case having synovial chondromatosis. CONCLUSIONS: Baker cysts
      are common and usually are not associated with complications. In our series, a
      prevalence of 6.8% of complicated cysts was observed, either by their contents or
      wall changes. The most common complication is rupture (50% of complicated cysts)
      which can be asymptomatic in up to 80% of cases, followed by free intracystic
      bodies (40% of complications) usually of degenerative origin. The complication is
      statistically associated with meniscal ruptures and aged patients.

PMID- 11447902
TI  - [Mucormycosis: a classical infection with a high mortality rate. Report of 5
      cases].
AB  - Mucormycosis is an infection caused by fungi in the Mucorales order, of which the
      most relevant family is Mucoraceae, which includes the Rhizopus, Mucor and
      Absidia genera. It is a severe infection which involves diabetic patients with
      ketoacidotic decompensation and immunosuppressed patients. We report here five
      cases (four with rhino-cerebral forms) attended at our hospital in the last ten
      years. Three patients had diabetes, one was infected with the human
      immunodeficiency virus, and the other was on a programme of peritoneal dialysis
      due to renal failure. The most relevant clinical manifestation was the presence
      of the necrotic lesion in three of the four patients with rhinocerebral
      involvement (two in the palate, one in the nasal mucosa). Two patients died as a
      result of the direct infection a few days after diagnosis. In summary,
      mucormycosis is an infection with a low prevalence but still maintaining a high
      mortality rate. An early diagnosis is essential and thereby a high index of
      clinical suspicion is required in patients with predisposing factors.

PMID- 11447903
TI  - [Medical relevance of the identification of human pathogenic fungi to species
      level].

PMID- 11447904
TI  - [Indications for the non-surgical revascularization in ischaemic heart disease].

PMID- 11447905
TI  - [Indications for repeating a bronchoscopy. Relevance of a second bronchoscopy
      suspecting a malignant condition].

PMID- 11447906
TI  - [Value of detecting autoantibodies in glomerular pathology].

PMID- 11447907
TI  - [Biological bases of migraine].

PMID- 11447908
TI  - [Pegylated interferons: preliminary review of their pharmacokinetic
      characteristics].

PMID- 11447909
TI  - [Sudden onset of tight hydropneumothorax, esophageal perforation (Boerhaave
      syndrome)].

PMID- 11447910
TI  - [71 Year-old woman with left coxaglia. Chondrosarcoma].

PMID- 11447911
TI  - [Persistant fever and generalized scaly rash in a 3 year-old female child.
      Kawasaki disease with coronary aneurysms].

PMID- 11447912
TI  - [Miliary pattern in an HIV infected patient on tuberculostatic therapy.
      Paradoxical reaction of tuberculosis during antiretroviral therapy].

PMID- 11447913
TI  - [Large encapsulated hepatic mass. Hepatocarcinoma].

PMID- 11447914
TI  - [Merkel cell carcinoma in a kidney transplant patient].

PMID- 11447915
TI  - [Melkersson-Rosenthal syndrome: diagnostic considerations].

PMID- 11447916
TI  - [Papular purpuric "gloves and socks" syndrome secondary to parvovirus B19
      infection].

PMID- 11447917
TI  - [Urinary pheochromocytoma with normal hormone levels].

PMID- 11447918
TI  - [Salmonella enteritidis meningitis].

PMID- 11447919
TI  - [Rhabdomyolysis complicated with acute renal insufficiency in a patient treated
      with gemfibrozil and cerivastatin].

PMID- 11447920
TI  - Perinatal medicine in developing countries.

PMID- 11447921
TI  - Maternal and perinatal mortality. Tuzla statement.

PMID- 11447922
TI  - Perinatal problems in developing countries: lessons learned and future
      challenges.
AB  - Every year, approximately 600,000 women die of pregnancy-related causes--98% of
      these deaths occur in developing countries. Complications of pregnancy and
      childbirth are the leading cause of death and disability among women of
      reproductive age in developing countries. Of all human development indicators,
      the maternal mortality ratio shows the greatest discrepancy between developed and
      developing countries. In fact, maternal mortality itself contributes to
      underdevelopment, because of its severe impact on the lives of young children,
      the family and society in general. Furthermore, in addition to more than half a
      million maternal deaths each year 7 million perinatal deaths are recorded and 8
      million infants die during the first year of life. Maternal morbidity and
      mortality as well as perinatal mortality can be reduced through the synergistic
      effect of combined interventions, without first attaining high levels of economic
      development. These include: education for all; universal access to basic health
      services and nutrition before, during and after childbirth; access to family
      planning services; attendance at birth by professional health workers and access
      to good quality care in case of complications; and policies that raise women's
      social and economic status, and their access to property, as well as the labor
      force.

PMID- 11447923
TI  - Antenatal care in developing countries. What should be done?
AB  - Development of antenatal care from the beginning of the 20th century and its
      relation to perinatal mortality in developed countries is presented. The role of
      socioeconomic factors, new diagnostic and therapeutic procedures, extended
      indications for cesarean section and of neonatal intensive care is also stressed.
      In the West- and Middle-European countries by the introduction of antenatal care
      the perinatal mortality (PNM) rate decreased from about 60.0@1000 in the years
      1920-1930 to about 40.0@1000 in 1950s. Further decrease to about 25.0@1000 in the
      1970s was conditioned by an increase of number of antenatal visits and by
      extended indications for cesarean section. New technologies (amnioscopy,
      pH.metry, cardiotocography and ultrasound examinations) decreased the PNM rate to
      about 13.0@1000 in the year 1980. Regional organization with neonatal intensive
      care units decreased PNM rate to low values of 5.0-9.0@1000. The echo of the
      number of antenatal visits to PNM rate is illustrated on 36,855 deliveries at the
      University Clinic in Zagreb. In developing countries maternal and perinatal
      mortality is very high. The reason for that is a bad socioeconomic background and
      a lack of organized antenatal and perinatal health care system. The policy to
      decrease maternal and perinatal mortality is presented: the improvement of
      antenatal booking and of the number of prenatal visits of pregnant women; their
      childbearing under professional assistance. The organizing of maternity health
      care should be different from country to country, from region to region,
      respectively.

PMID- 11447924
TI  - A simple, efficient and inexpensive program for preventing prematurity.
AB  - Prevention of prematurity and of low birth weight is--because of the associated
      increased risk of mortality and morbidity--one of the most urgent tasks of
      perinatal medicine. Whereas the rate of prematures all over the world does not
      vary very much (5-10%), the rate of infants born with low birth weight lies
      between 3.6% and 10% in the industrial countries and between 9.8% and 43% in the
      developing countries, where the main cause of low birth weight is intrauterine
      malnutrition. As there are different causes for prematurity and low birth weight,
      but also because various countries have different resources and have therefore to
      set their priorities differently, there is no global solution. The situation in
      each country must be considered individually. However, as far as basic means are
      available for the majority--such as basic health care, monitoring the nutritional
      state of the mothers and acting to prevent infectious diseases (malaria in
      particular can cause prematurity)--determined prevention of prematurity should
      take the form of screening and the treatment of disturbances of the vaginal
      milieu or genital infections. This policy can be recommended because one of the
      most important avoidable causes of prematurity is ascending genital infection
      (mostly combined with bacterial vaginosis), which very frequently starts with a
      disturbance of the vaginal milieu and then often takes its course
      asymptomatically. Regular screening for signs of such a disturbance using vaginal
      pH-measurements (and if necessary further diagnostics and therapy) makes possible
      the detection of an "early marker" to prevent prematurity in an effective and
      inexpensive way. Our prematurity-prevention-program, which has been successful
      for many years, is based on an anamnestic assessment of prematurity risk, the
      early detection of warning signs (including regular measurement of the vaginal
      pH) and, if necessary, the appropriate therapeutic measures. In cases of
      disturbance of the vaginal milieu, the latter consists of a therapy with
      lactobacillus preparations or in a combination of lactobacillus preparation with
      an acidifying therapy which may lead to earlier normalization of the vaginal
      milieu. In cases of bacterial vaginosis local therapy, for example with
      metronidazol or clindamycin, is undertaken, and in other infections specific
      treatment. It is encouraging to note that particularly the rate of the very small
      prematures is reduced when pregnant patients take part in our self-care-program,
      measuring their own vaginal pH-value twice a week, and also searching for any
      other warning signs. In this way in our collective the rate of very small low
      birth weight infants could be reduced from 7.8% in the immediate previous
      pregnancy to 1.3%. In a prospective study performed in Erfurt the rate of very
      early premature births (< 32 + 0 gw) amounted to only 0.3% in contrast to 3.3% in
      a control group who had not taken part in the self-care activity. According to a
      differentiated classification of the control group the success of the self-care
      activity was even clearer: In patients who did not take part because their
      doctors did not support the self-care activity, the rate of very early premature
      births amounted to 4.1%. In patients who did not take part in the self-care
      activity, but who were in the care of doctors who were interested and had taken
      part in the prevention-program, the rate was 2.2%; in the group with active
      participation in the self-care activity it was only 0.3%. To date measurement of
      the vaginal pH-value was performed intravaginally using either indicator strips
      or pH-measuring test gloves. A short time ago we developed a panty liner coated
      with an indicator strip, which enables reading of the pH-value by just checking
      the indicator on the panty liner. First results with this panty liner are very
      promising.

PMID- 11447925
TI  - The use of first trimester ultrasound in routine practice.
AB  - Since the introduction of ultrasound scanning in early pregnancy, transabdominal
      or transvaginal ultrasonography has taken on an important role in routine
      clinical practice in terms of the care of the fetus and the mother. The use of
      ultrasound in very early pregnancy makes it possible to confirm the intrauterine
      living embryo or diagnose the extrauterine pregnancy in which medical treatment
      with low morbidity is feasible with early detection. Early scanning can provide
      exact dating with acceptable error, which is one of problems encountered in
      clinical practice. Chorionicity can be correctly established by early scanning
      (before 14 weeks of gestation) to manage multiple pregnancies properly. The
      nuchal translucency, which is a transitory abnormality, can be measured for the
      early screening of Down's syndrome, trisomy-18, trisomy-13, Turner's and some
      other aneuploidy at the 11-14 weeks gestation with approximately 80% detection
      rate. Early diagnosis of some major abnormalities such as anencephaly,
      megacystis, polycystic kidney, omphalocele is also possible by early scanning.
      This provides great advantages as the clinical management will be quite different
      for a case of omphalocele or megacystis. Therefore the early ultrasound scanning
      has become a routine standard method in the care of the pregnant woman.

PMID- 11447926
TI  - Antepartal assessment of IUGR fetuses.
AB  - Intrauterine growth restriction (IUGR) should be defined on the basis of a
      prenatally recognized defective growth compared to that expected for this fetus.
      This condition is encountered in 10-15% of the pregnancies and the perinatal
      outcome is impaired mainly as a consequence of fetal hypoxemia that is present in
      30% of IUGR fetuses. In order to allow for proper management, the IUGR should be
      recognized prenatally and the method of choice for this purpose is ultrasound
      fetal biometry. After the identification of IUGR, 2nd level tests should be
      performed in order to assess the fetal oxygenation conditions. The validity of
      Doppler investigation on fetal and umbilical vessels is discussed, and the
      importance of using computer assisted cardiotocography instead of traditional eye
      ball evaluation of the non-stress test is emphasized.

PMID- 11447927
TI  - Genetic components of perinatal morbidity and mortality.
AB  - The authors summarize the perinatal effects of the main genetic disorder
      groupings. Diseases of autosomal dominant inheritance are usually less severe and
      postnatal life is possible. Diseases of autosomal recessive inheritance are
      serious in most cases, causing severe symptoms in postnatal life. Diseases of X
      linked recessive inheritance manifest themselves in male embryos and may be mild
      or serious; the more severe forms may influence the perinatal outcome. Diseases
      of X-linked dominant inheritance occur less frequently and manifest themselves in
      both sexes: in some cases the life expectancy is not favorable. Chromosomal
      anomalies, unbalanced rearrangements and autosomal trisomies may cause severe
      multiplex malformation syndromes and mental retardation. The diseases are serious
      in most cases and intrauterine mortality is high. Conversely, in cases of
      numerical differences of the sex chromosomes perinatal mortality does not
      increase remarkably, except in X-monosomy. Diseases of multifactorial origin lead
      to isolated malformations, but many civilization diseases originate from similar
      causes. In a few cases, severe diseases (i.e. congenital heart defects and neural
      tube defects) occur which may influence the outcome of the pregnancy. In terms of
      teratogenic effects, taking medication or undergoing X-ray examination or
      infections during early pregnancy indicates only a small risk in most cases. The
      authors emphasize that genetic centers significantly influence the perinatal
      outcome of pregnancies with their complex activity and their role in prenatal
      diagnostics.

PMID- 11447928
TI  - Eclampsia: a leading cause of maternal mortality.
AB  - Eclampsia is the occurrence of generalized convulsions during pregnancy, labor or
      within seven days of delivery, not due to epilepsy or other convulsive disorders.
      It is largely a preventable disease provided the pregnant women get regular
      antenatal care. Despite all prevention measures, diagnostic modalities and
      intensive treatment, it is still one of the leading causes of maternal mortality
      in the developing world. In this review, we present definitions, epidemiologic
      data, pathophysiology, diagnosis and management of this life threatening
      condition.

PMID- 11447929
TI  - Hemostatic problems before, during and after delivery.
AB  - Normal pregnancy and childbirth are known to be associated with marked changes in
      the coagulation and fibrinolytic systems. Generally, enhancement of clotting
      activity persists to prevent the risk of major hemorrhage. Hemostatic problems,
      either associated with a specific complication of pregnancy and labor or due to a
      hereditary or acquired bleeding diathesis or thrombophilias, present a
      significant cause of maternal and neonatal morbidity and mortality. This article
      reviews hemostatic disorders in pregnancy and the peripartal period from the
      standpoint of the obstetrician.

PMID- 11447930
TI  - Perinatal mortality in the Federation of Bosnia and Herzegovina.
AB  - AIM: The aim of the study was to investigate the most frequent causes of
      perinatal mortality in Bosnia and Herzegovina. METHODS: We analyzed in a
      retrospective study over a one year period (1999) the following cantons:
      Sarajevo, Mostar, Tuzla, Bihac, Gorazde, Travnik, Zenica, which represent about
      one half of the population of Bosnia and Herzegovina. RESULTS: Perinatal
      mortality in the analyzed regions within Bosnia and Herzegovina was 19.55@1000,
      which is unacceptable in comparison with developed countries. Early neonatal
      mortality (9@1000) was lower than late fetal mortality 10.55@1000. The most
      frequent causes of death were: premature birth, 6.32% of all deliveries; EPH
      gestosis with a rate of 9% of all deliveries and fetal anomalies with 0.68% of
      all deliveries. In Bosnia and Herzegovina, prematurity is the cause of early
      neonatal mortality in 78.5% of cases, while fetal anomalies are the cause in the
      early new-born period in 10.70% of cases. CONCLUSION: The results of perinatal
      mortality analyses in Bosnia and Herzegovina confirm that perinatal mortality
      directly depends on the development of the health care system, economic
      sustainability, and living conditions. Our results show that Bosnia and
      Herzegovina fall into the category of developing country with a perinatal
      mortality rate of 19.55@1000.

PMID- 11447931
TI  - Management trend and safety of vaginal delivery for term breech fetuses in a
      tertiary care hospital of Karachi, Pakistan.
AB  - AIM: To investigate the safety of vaginal delivery for term breech fetuses in a
      tertiary-care hospital of Pakistan. METHODS: We reviewed the medical records of
      all live singleton breech deliveries at or beyond 37 weeks of gestation, at the
      Aga Khan University Hospital, Karachi, from January 1988 to December 1995.
      RESULTS: Rate of cesarean section increased from 48% (1988) to 74% (1995). Out of
      287 subjects, 158 underwent elective cesarean section while 129 received a trial
      of labor, 77% of which delivered vaginally. There was no neonatal or maternal
      death. Compared to babies delivered by emergency or elective cesarean section,
      those delivered vaginally had significantly more neonatal intensive-care unit
      admissions (none and 5% versus 13%) and higher rates of birth trauma (none and
      0.6% versus 7%). However, there was no significant difference in the Apgar score
      at 5 minutes and the risk of maternal complications by delivery mode. CONCLUSION:
      Allowing trial of labor to carefully selected mothers can result in vaginal
      delivery in 77% of the cases. However, the risk of trauma and neonatal intensive
      care unit admissions, among vaginal births may favor the decision of elective
      cesarean section, unless rigorous pre-delivery assessment and conduct of delivery
      by adequately trained obstetricians is performed.

PMID- 11447932
TI  - Post-partum hysterectomies: revisited.
AB  - This retrospective case analysis is performed in order to analyze post-partum
      hysterectomies in St. Mary's Hospital, Manchester during the last thirteen years
      and to compare it with the published results twenty years ago. We wanted to
      determine any possible changes in trends as well as to discuss the place of post
      partum hysterectomy in modern obstetric practice. The main outcome measurements
      were incidence, maternal mortality and morbidity, indications and risk factors
      for post-partum hysterectomy in our hospital today and twenty years ago. Obtained
      results were compared to the same data and trends world-wide. There has been a
      fall in the incidence of both, elective and emergency post-partum hysterectomies
      in St. Mary's Hospital. All together, 28 women underwent post-partum hysterectomy
      electively or as an emergency in the period between 1985 and 1997. Mortality rate
      was 1 in 28 cases and morbidity rate was 65% in emergency group and 37.5% in
      elective group. The most common indication for elective post-partum hysterectomy
      is cervical intraepithelial neoplasia. The most important risk factor for
      emergency post-partum hysterectomy is previous cesarean section especially
      related to placenta accreta. There was no significant changes in trends, maternal
      mortality and morbidity and indications related to emergency post-partum
      hysterectomies today and twenty years ago, while the indications for elective
      cases were changed.

PMID- 11447933
TI  - Sex ratio imbalance and Down's syndrome newborns.

PMID- 11447934
TI  - Ultrastructure of spermatogonia and primary spermatocytes of C57BL6J mice.
AB  - The three types of spermatogonia were confirmed. Type A spermatogonia have a
      large nucleus and loose chromatin and are poor in endoplasmic reticulum. The
      second type, B spermatogonia, have rounded and smaller nuclei filled with more
      electron-dense nucleoplasmic material. The endoplasmic reticulum has the aspect
      of round or elongated cisterns that are free in the cytoplasm or close to the
      basement membrane. In contrast, intermediate spermatogonia present chromatin
      material with intermediate condensation compared with the two previous cell
      types. Primary spermatocytes are characterized by the presence of intercellular
      bridges and a synaptonemal complex. In the late pachytene stages, the
      synaptonemal complex was found to be enveloped by chromatin material.

PMID- 11447935
TI  - Comparative anatomical study on fissura nasolacrimalis and nasomaxillaris in
      skull of the Korean native goat (Capra hircus).
AB  - We found specific anatomical structure on the fissura nasolacrimalis and fissura
      nasomaxillaris of the skull of the Korean native goat. It has quite a wide
      opening on each side of the os nasale and could be classified into four types
      according to various patterns of articulations of the neighbouring bones.

PMID- 11447936
TI  - Mucous cells in micropogonias furnieri gills: histochemistry and ultrastructure.
AB  - The characteristics of the mucous cells located in the gills of the fish
      Micropogonias furnieri were investigated. Using histochemical procedures that
      included methods for localization and characterization of glycoproteins (GPs), no
      differences were detected between the mucous cell contents of the primary and
      secondary lamellae. The GPs were identified with (a) oxidizable vecinal diols;
      (b) sialic acids and some of their chain variants, C7 or C9; (c) carboxyl groups
      and (d) sulphate groups. The electron microscope showed large mucous globules of
      different electro densities from mucous cells located deep in the epithelium
      between the other epithelial cells; the release of mucus by exocytosis was
      observed. GPs secreted on the surface of the mucous cells was suggested to be
      important for the lubrication, protection and inhibition of microorganisms. It is
      possibility that GPs could have similar roles in Micropogonias furnieri gills.

PMID- 11447937
TI  - Human foetal sacral length measurement for the assessment of foetal growth and
      development by ultrasonography and dissection.
AB  - This study investigated the value of prenatal ultrasonographic measurements of
      sacrum as a predictor of in utero development and gestational age (GA), and to
      make a comparison between the data obtained by ultrasonography and dissection. A
      prospective cross-sectional study of ultrasonography was conducted in 186
      pregnant women with uneventful single pregnancies. GA ranged from 14 to 40 weeks,
      and the relationships of sacrum length (SL) with GA, femur length (FL),
      biparietal diameter (BPD), head circumference (HC) and abdominal circumference
      (AC) were evaluated. In addition, the sacral bones of 101 spontaneously aborted
      foetuses aged from 13 to 39 weeks were dissected and measured. The relationship
      of the results with GA was investigated. There was a linear relationship between
      the ultrasonographic measurements of the SL and the GA (R2 = 0.93, P < 0.001),
      the FL (R2 = 0.93, P < 0.001), the BPD (R2 = 0.93, P < 0.001), the HC (R2 = 0.92,
      P < 0.001) and the AC (R2 = 0.90, P < 0.001). The rate of increase of SL was
      significantly higher before 28 weeks of gestation than in later pregnancy, with a
      correlation coefficient between SL and GA of 0.96 and 0.88, respectively. The SL
      measurements obtained by dissection were similar to those of ultrasonography.
      There was a linear relationship between the SL and the GA (R2 = 0.96, P < 0.001)
      and the correlation coefficients between SL and GA were 0.97 before 28 weeks of
      gestation, and 0.94 in later weeks. In conclusion, this study demonstrates a high
      correlation between the SL, GA and other standard measurements of foetal growth,
      and suggests that SL measurement is a valuable predictor of GA in the foetuses
      with normal growth.

PMID- 11447938
TI  - Characteristics of dorsal lingual papillae of the Bactrian camel (Camelus
      bactrianus).
AB  - The morphology of dorsal lingual papillae of the Bactrian camel (Camelus
      bactrianus) was studied by using light and scanning electron microscopy. Filiform
      and lenticular papillae were considered as mechanical papillae but fungiform and
      vallate papillae were considered as gustatory papillae. Filiform papillae were
      distributed mostly in the anterior two-thirds region of the tongue. Each filiform
      papilla consisted of one primary papilla and a few smaller secondary papillae.
      Lenticular papillae were distributed on the torus linguae. The larger papillae
      were arranged in two parallel lines medially whereas the smaller papillae were
      laterally located. Most of the fungiform papillae were found on the lateral
      margins of the anterior two-thirds of the tongue. These papillae were small and
      round. Intra-epithelial taste buds were located on the dorsal surface of each
      papilla. The vallate papillae were arranged in two rows on each rim of the torus
      linguae. Each round- and flat-shaped vallate papilla was surrounded by a
      prominent gustatory groove and an annular pad. A few taste buds were observed in
      the lateral epithelium of the papillae. The keratinization of the covering
      stratified squamous epithelium of the mechanical lingual papillae was relatively
      thicker than those of the gustatory papillae. The lingual papillae of the
      Bactrian camel exhibited some different characteristics from other domestic
      ruminants. These morphological characteristics of the tongue of the Bactrian
      camel might have evolved to assist the camel in prehension and manipulating of
      the inorganic stiff plants that grow in its environment and therefore might
      relate to the feed and feeding habits of the animal.

PMID- 11447939
TI  - Immunohistochemical localization of progesterone receptor isoforms in the chick
      pre-follicular ovary.
AB  - The distribution of progesterone receptor A and B isoforms in different cell
      types of the chick pre-follicular ovary was studied by immunohistochemistry.
      Newly hatched chicks were killed and the left ovary was removed, fixed and
      embedded in paraplast. Sections (5 microns thick) were made for the detection of
      progesterone receptor isoforms, using a technique of indirect immunoperoxidase.
      The results indicate that progesterone receptors were localized in the nuclei of
      germinal epithelium and germ cells of the ovarian cortex and in the interstitial
      and epithelial cells of the lacunar channels of the ovarian medulla.
      Undifferentiated cells did not present progesterone receptors. In all cell
      subpopulations progesterone receptor B was the predominantly expressed isoform.
      These data suggest that progesterone receptor isoforms are differentially
      expressed in the chick pre-follicular ovary and that progesterone effects in this
      tissue are mediated by the progesterone receptor B isoform.

PMID- 11447940
TI  - Confocal scanning laser microscopy examination of bovine vaginal fluid at
      oestrus.
AB  - This article reports the study of the structural elements of bovine vaginal fluid
      at oestrus using a confocal scanning laser microscope (CSLM) to examine samples
      collected from 10 lactating cows at the time of insemination. The filamentous
      glycoproteins, which form the structural component of vaginal fluid, were stained
      with fluorophore acridine orange for 10 min. This microscopy technique permits
      visualization of a network of non-oriented filaments of different thickness in a
      three-dimensional array. This arrangement was repeated throughout the sample and
      was common to all samples. Interfilament spaces varied in width between cows and
      ranged from 1 to 20 microns. The present results provide a new, non-aggressive
      technique for the study of biological samples that show hydrogel-like behaviour.
      Due to its simplicity, the CSLM technique proposed offers the advantages of (1)
      providing realistic images of vaginal fluid structure, free from artifacts
      arising from sample preparation, and (2) the possibility of observing specimens
      shortly after collection. CSLM proved to be a useful tool for the examination of
      vaginal fluid and may also serve as a good control for artifacts associated with
      scanning electron microscopy procedures.

PMID- 11447941
TI  - Ultrastructure of centrifuged bovine oocyte-cumulus complexes after pre-treatment
      with cytoskeletal relaxant.
AB  - The objective of this study was the electron microscope examination of the
      localization of lipid droplets, mitochondria and other intracellular organelles
      in bovine oocytes and cumulus cells after Cytochalasin B pre-treatment and ultra
      centrifugation. Bovine (n = 180) oocyte cumulus complexes on a germinal vesicle
      stage were treated with 5 micrograms/ml Cytochalasin B at 38.5 degrees C for 10
      15 min. They were then centrifuged at 15,800 g and fixed at 39 degrees C
      immediately after centrifugation in 3% glutaraldehyde with 0.5% formaldehyde for
      the microscopic examinations. The centrifugal pole of the oocytes was filled with
      mitochondria. The centripetal part contained lipid granules and vesicles.
      Cytoplasm of low density was located in the equatorial region. Hyaloplasm with
      spontaneously formed membrane and non-membrane vacuoles was located in a supra
      equatorial zone of the oocytes. In the cumulus cells the lipid vesicles formed
      one dark mass in the centripetal pole. The nuclei of these cells were deformed
      and vacuolization of the cytoplasm was noted.

PMID- 11447942
TI  - Proliferation in the gastric epithelium of bovine abomasum during foetal
      development as revealed by Ki-67 immunocytochemistry.
AB  - For the first time, proliferative cells in the abomasal mucosa of 30 bovine
      foetuses with a crown-rump length of 34 to 1000 mm (approximately 45-250 days of
      gestation) were detected using the antibody MIB-1 against the (human) nuclear
      associated protein Ki-67. At the beginning of mucosal development, the epithelium
      is stratified and MIB-1 positive cells are scattered all over the epithelium.
      With the formation of gastric pit/gland invaginations, the proliferative cells
      are mostly confined to the basal half or third of the gastric pit/gland unit,
      both in the regio glandulae propriae and in the regio glandulae pyloricae. From
      the 27th week in the regio glandulae propriae and the 30th week in the pyloric
      gland region, respectively, the proliferative cells move upwards and are situated
      in the bottom of the pit and the upper part of the gland, whereas the base of the
      gland is free of labelling.

PMID- 11447943
TI  - Contribution to the development of the stapedius muscle structure in human
      fetuses.
AB  - The purpose of this report is to contribute to the knowledge of the morphogenesis
      of the human stapedius muscle. We have studied the stapedius structure
      development in 17 temporal bones from human fetuses. Chronological ages were from
      48 days (21 mm) to 29 weeks (270 mm). Samples were fixed in 10% formol,
      decalcified with 2% nitric acid, embedded in Paraplast, sectioned in sequence of
      7 microns and were stained with haematoxylin & eosin and Martins' trichrome. Four
      maturation stages were observed in the development of the stapedius muscle
      structure. First, the formation of the 'primordium muscularis' in the mesenchyme
      of the tympanic cavity (promyoblasts) was observed in a 36-mm embryo. Second, its
      differentiation into myoblasts, and its next cellular fusion to form muscle
      tubes, was seen in a 99-mm foetus. In the third stage, myofibrogenesis phenomena
      were developed, to synthesize, the myotube myoblasts, myofilaments, phenomena we
      observed that took place during the 14th to 17th weeks of development. The last
      stage was characterized by the presence of striated muscle fibres, at first
      intermingled with myotubes (18th to 26th weeks), until in the 29th week fetuses
      (270 mm) the skeletal muscle fibre was completely differentiated. We conclude
      that in the 29th week of development (270 mm) the stapedius muscle structure is
      completely differentiated, although the functional development is not complete
      until birth.

PMID- 11447944
TI  - The position and shape of osteophyte formations at canine vertebral endplates and
      its influence on radiographic diagnosis.
AB  - The relationship between the risk of missing osteophytes in lateral radiographs
      and their position was determined in a sample of German shepherd dogs (GSDs, n =
      42) and dachshunds (DHs, n = 36). Only 10% of osteophytes which were not detected
      on radiographs were located in the ventral median area (position 1) and
      classified as type 1 (small spur with narrow base). The highest risk for being
      affected next to the intervertebral foramen and/or the dorsal area of the
      vertebral endplate (position 3) was noticed in the lumbar segment (95% CI: 5.2
      9.8% in DHs; 11.9-17.7% in GSDs). The minimum risk of missing osteophytes in this
      position radiologically was 33.3% in the GSDs and 26.4% in the DHs. In the GSDs a
      higher proportion of type 2 osteophytes (spur with broader base of origin,
      tending to extend up to half the way along the disc space) was not visualized on
      radiographs. Peak incidences of osteophytes in positions 1 and 3 were located at
      the centres of spinal flexion and extension. Therefore, distribution patterns of
      osteophytes in these positions confirmed mechanical factors being important in
      pathogenesis of vertebral osteophytosis.

PMID- 11447945
TI  - Comparative anatomy of the male guinea-pig and human lower urinary tract:
      histomorphology and three-dimensional reconstruction.
AB  - The guinea-pig is often used for experimental studies in urology. However, the
      anatomy of the lower urinary tract of the guinea-pig is poorly described in the
      literature. The structure and function of the lower urinary tract, i.e.
      continence, micturition and sexual function, are closely related to the gross
      anatomy of the pelvis and the fine structure of the musculature. We investigated
      the anatomy and histomorphology of the lower urinary tract by serial sections in
      male guinea-pigs and compared it to that in humans. Immunohistochemical stainings
      for alpha-smooth muscle cell actin were used to differentiate between smooth and
      striated muscles. By using whole pelvic preparations, including all internal
      organs preserved in their in situ location for three-dimensional reconstruction,
      we developed three-dimensional models, which elucidate the spatial relationship
      of all muscular structures and can help to deduce functional aspects of lower
      urinary tract function. In the guinea-pig, most of the muscles found in humans
      can be demonstrated in comparable location and extension. However, the structure
      of the prostate and the existence of the so-called coagulation glands define a
      significant difference in the morphology of the prostatic urethra.

PMID- 11447946
TI  - Soft tissue is not just Kleenex.

PMID- 11447947
TI  - Year one dental visit.

PMID- 11447948
TI  - Dental caries in adolescents associated with caffeinated carbonated beverages.
AB  - Dental caries is an infectious disease involving all age groups. Adolescence is a
      period in which the risk for dental caries remains especially high. Many factors,
      some unique to the teenage years, contribute to the initiation and progression of
      dental caries in this age group. One factor with the potential for being
      significant is the adolescent diet, especially the high consumption of sugars.
      One product that tends to contribute to the amount of sugar ingested is
      carbonated beverages. Many soft drinks also contain significant amounts of
      caffeine. Regular caffeine ingestion may lead to increased, even habitual, usage.
      It is suggested that the combination of the consumption of highly sweetened soft
      drinks and habitual usage of caffeine may significantly increase a susceptible
      adolescent's potential for developing dental caries. Cases are presented
      demonstrating the early initiation and rapid progression of dental caries in
      three adolescents. A common factor is the ingestion of high amounts of
      caffeinated-carbonated soft drinks.

PMID- 11447949
TI  - The sensitivity and specificity of clinical assessment compared with bitewing
      radiography for detection of occlusal dentin caries.
AB  - PURPOSE: This prospective, cross-sectional study examined the sensitivity and
      specificity of clinical assessment compared to bitewing radiographs in the
      detection of occlusal dentin caries in permanent molars. METHODS: Subjects were
      481 children aged 5-12 years from a school-based dental clinic. Occlusal surfaces
      of 1929, sealed and unsealed first and second permanent molars were examined
      clinically and scored using specific criteria. Teeth with any type of
      restorations or proximal caries, including preventive resin restorations, were
      excluded from the study. Bitewing radiographs were exposed within 4 weeks of
      clinical examination and were assessed for dentin radiolucencies beneath the
      occlusal surface. The results of the clinical examinations were correlated with
      those of bitewing radiographs. Information provided by the parents on history
      forms, including systemic fluoride exposure, was also noted. RESULTS: Of the 1833
      teeth scored as clinically sound in the study, only 72 (4%) demonstrated a dentin
      radiolucency on bitewings, and 1761 (96%) were scored as sound. The sensitivity
      of the clinical examination was determined to be 0.96. In the teeth clinically
      scored as showing dentin caries, only 56/96 (58%) were found to have dentin
      radiolucencies on the radiographs. The specificity of the technique was
      determined to be 0.58. A positive history of a medical condition, or fluoride
      exposure, in the forms of toothpaste use, or water fluoridation did not affect
      the examination results. CONCLUSIONS: Clinical examination of cleaned and dried,
      sealed, and unsealed teeth has a sensitivity of 0.96 and a specificity of 0.58 in
      the detection of dentin radiolucencies in bitewing radiographs. Dentin
      radiolucencies beneath clinically sound occlusal surfaces are not significantly
      associated with gender, medical conditions or fluoride.

PMID- 11447950
TI  - A survey of pediatric dentists' management of dental caries in children three
      years of age or younger.
AB  - PURPOSE: The purpose of this investigation was to obtain information from
      practicing pediatric dentists about how they manage caries in children three
      years of age and younger and the problems they are encountering. METHODS: A
      survey mailed to a randomly selected sample of 1,000 members of the American
      Academy of Pediatric Dentists (AAPD) in January of 1997 asked them to: identify
      the types and extent of caries in the young age group; define and quantify
      methods used to manage caries; determine the representation of caries among
      different payer source groups; identify sources of information used in managing
      caries; and determine the criteria they use for assessing the success of
      different methods in managing caries. RESULTS: The response rate was 43%.
      Definitions of techniques of managing caries varied among practitioners, and the
      use of the methods differed for the different degrees of severity of caries.
      There was a significant relationship between the percentage of Medicaid in a
      practice and the percentage of children with caries and pulpal involvement.
      Personal experience/philosophy was most frequently identified as an important
      source among factors influencing treatment decisions and sources of information
      about managing. Criteria most frequently cited to determine effectiveness of
      treatment were "caries free at recall" (45%) and "stop progress of lesion" (30%).
      CONCLUSION: Practitioners use a variety of techniques to manage caries in the
      child < or = 3 years of age. Disease level and payer source factored heavily in
      their treatment decisions. Practitioners reported interest in receiving
      information and help from AAPD on the subject.

PMID- 11447951
TI  - Alternative method of hemorrhage control in full strength formocresol pulpotomy.
AB  - PURPOSE: This investigation evaluated the success of a formocresol pulpotomy
      technique in which hemostasis was obtained with the same formocresol dampened
      cotton pellet used to medicate the root pulp stumps and to compare the findings
      of this investigation with data of published formocresol pulpotomy studies in
      which hemorrhage was controlled by traditional means. METHODS: Clinical and
      radiographic data were available for 194 primary molars in 112 patients with
      follow up times ranging from 5 to 109 months (mean = 38 months). RESULTS: Overall
      radiographic success was 87%. The most frequently observed pulpal responses were
      calcific metamorphosis (34%) and internal resorption (10%). Overall clinical
      success was 98%. Only 7 of 194 molars were extracted due to radiographic and/or
      clinical failure. Overall cumulative probability of survival remained high over
      time with a cumulative survival rate of over 94% over 4 years. CONCLUSIONS: The
      success rates for this variation of the formocresol technique are comparable to
      those success rates in the literature where hemostasis was obtained in a separate
      step using a nonmedicated cotton pellet. The results of this study suggest that
      using the same cotton pellet dampened with full strength formocresol to obtain
      hemorrhage control and medicate the root pulp is an acceptable variation of the
      traditional formocresol pulpotomy technique.

PMID- 11447952
TI  - A comparison of two oral ketamine-diazepam regimens for the sedation of anxious
      pediatric dental patients.
AB  - PURPOSE: This study compared 2 oral ketamine-diazepam regimens (8 mg/kg and 10
      mg/kg of ketamine in combination with 0.1 mg/kg diazepam) in preschool age
      children with respect to physiological, behavioral and amnestic parameters.
      METHODS: Twenty-five children completed the double-blind, crossover design.
      Physiologic, behavioral and amnestic effects were evaluated. RESULTS: ANOVA
      demonstrated significant changes in systolic blood pressures and heart rates in
      both the 8 mg/kg group and 10 mg/kg group (P < 0.05), as well as significant
      changes in diastolic blood pressures in the 10 mg/kg group (P < 0.05). However,
      these changes were not clinically significant. Success rates were 28% for the 8
      mg/kg dosage and 44% for the 10 mg/kg dosage. There was a cumulative vomiting
      rate of 50% and a psychic phenomena rate of 10%. There were no statistically
      significant differences between the two dosages with regard to success rates,
      postoperative vomiting, or psychic phenomena using McNemar's test. CONCLUSIONS:
      There is no advantage of 10 mg/kg dose of ketamine over the 8 mg/kg dose.
      Ketamine did not demonstrate amnestic effects in this study. There were
      statistically but no clinically significant changes in physiological parameters
      in either group. This study does not support the use of either 8 mg/kg or 10
      mg/kg oral ketamine for the sedation of uncooperative children.

PMID- 11447953
TI  - Dentinogenesis imperfecta: an early treatment strategy.
AB  - Dentinogenesis imperfecta (DI) type 2 is a disease inherited in a simple
      autosomal dominant mode. As soon as the teeth erupt the parents may notice the
      problem and look for a pediatric dentist's advice and treatment. Early diagnosis
      and treatment of DI is recommended, as it may prevent or intercept deterioration
      of the teeth and occlusion and improve esthetics. The purpose of this article is
      to present the objectives, treatment options, and problems encountered in the
      treatment of DI in the early primary dentition. A two-stage treatment of a
      toddler under general anesthesia is described and discussed. This paper
      recommends for severe cases of DI two treatment stages performed under general
      anesthesia. Stage 1 is early (around age 18-20 months) and is directed to
      covering the incisors with composite restorations and the first primary molars
      with preformed crowns. Stage 2 (around age 28-30 months) seeks to protect the
      second primary molars with preformed crowns and cover the canines with composite
      restorations.

PMID- 11447954
TI  - Combined orthodontic and restorative care of early childhood caries and anterior
      crossbite: a case report.
AB  - This case report describes management of a 3-year-old child with early childhood
      caries and anterior crossbite. Restorative care was postponed until after
      crossbite correction to eliminate occlusal interferences associated with
      premature contact and a functional shift of the mandible. Crossbite correction
      was performed with a fixed anterior bite plane appliance, and comprehensive
      restorative care was performed under general anesthesia.

PMID- 11447955
TI  - Appliance for chronic drooling in cerebral palsy patients.

PMID- 11447956
TI  - Placement of a preformed indirect resin composite shell crown: a case report.

PMID- 11447957
TI  - Peripheral ossifying fibroma--a clinical evaluation of 134 pediatric cases.
AB  - PURPOSE: Reported clinicopathologic studies on the peripheral ossifying fibroma
      (POF), a reactive gingival lesion, have not addressed the pediatric population in
      specific detail. This study, the first devoted to children, investigated the
      clinical features of a large number of POFs and compared the findings to cases
      reported in the English language literature. METHODS: Detailed clinical and
      historical information of 134 surgically removed POFs in patients aged 1-19
      formed the basis of this study. Clinical manifestations, histogenesis, treatment
      rationale with pediatric considerations, and biologic behavior were emphasized.
      RESULTS: The POF was found more frequently in females (60%). It had a
      predilection for the maxillary gingiva (60%) and for the incisor/cuspid region.
      The average patient age was 14 years. Only 2 (1%) POFs were found to be
      unequivocally associated with primary teeth. The clinician seldom included the
      POF in the differential diagnosis. The recurrence rate after surgical excision
      was 8%. CONCLUSIONS: This study revealed that a POF arising from the periodontal
      ligament of a primary tooth is most likely a rare event. However, the pediatric
      patient with a POF has special management considerations compared to the adult.
      Because of the POF behavior pattern, a proper treatment protocol is warranted
      with close postoperative follow-up.

PMID- 11447958
TI  - Traumatic herniation of the buccal fat pad.
AB  - Two new cases of traumatic herniation of the buccal fat pad are presented. The
      herniated fat pad was repositioned in case 1 and was excised in case 2. There was
      no recurrence after surgery in each case. Reviewing the literature, the lesion
      usually occurred in infants or young children under the age of 4 years as a
      result of traumatic penetration of the buccal mucosa and buccinator muscle with a
      foreign object.

PMID- 11447959
TI  - Delayed tooth eruption associated with an ameloblastic fibro-odontoma.
AB  - Delayed eruption of a single primary tooth is an uncommon event. Excluding a
      previous traumatic insult, the presence of a pericoronal odontogenic cyst or
      neoplasm is the primary cause for this abnormality. This case report describes
      the clinical and radiographic features of an ameloblastic fibro-odontoma in a
      young child, who presented with delayed eruption of the primary mandibular canine
      and prominent buccal expansion. A differential diagnosis for mixed, radiolucent
      and radiopaque lesions of the jaws will be discussed.

PMID- 11447960
TI  - Demineralization around orthodontic brackets bonded with resin-modified glass
      ionomer cement and fluoride-releasing resin composite.
AB  - PURPOSE: Enamel demineralization adjacent to orthodontic brackets is one of the
      risks associated with orthodontic treatment. Glass ionomer cements have been
      shown to decrease enamel demineralization adjacent to brackets and bands but do
      not exhibit bond strengths comparable to resin composites. The purpose of this in
      vitro study was to compare a fluoride-releasing resin composite versus a resin
      modified glass ionomer cement for inhibition of enamel demineralization
      surrounding orthodontic brackets. METHODS: Forty-five teeth were randomly
      assigned to 3 groups of 15 teeth. Fifteen were bonded with Concise (3M), a non
      fluoride-releasing resin composite (control); 15 teeth were bonded with Light
      Bond (Reliance), a fluoride-releasing resin composite; and 15 teeth were bonded
      with Fuji Ortho LC (GC Corporation), a resin-modified glass ionomer cement. The
      teeth were placed in an artificial caries solution to create lesions. Following
      sectioning of the teeth in a buccolingual direction, polarized light microscopy
      was utilized to evaluate enamel demineralization adjacent to the orthodontic
      bracket. The area of the lesion was measured 100 microns from the orthodontic
      bracket and bonding agent. RESULTS: MANOVA (P < .0001) and Duncan's test (P <
      .05) indicated the resin-modified glass ionomer cement (Fuji Ortho LC) and the
      fluoride-releasing resin composite (Light Bond) had significantly less adjacent
      enamel demineralization than the non-fluoride-releasing resin composite control.
      However, there was no significant difference between the resin-modified glass
      ionomer cement and the fluoride-releasing resin composite. CONCLUSIONS: Based on
      the results of this in vitro study, it can be concluded that Fuji Ortho LC and
      Light Bond exhibit significant inhibition of adjacent demineralization compared
      to the non-fluoride-releasing control.

PMID- 11447961
TI  - Delayed tooth eruption: association with severity of HIV infection.
AB  - PURPOSE: HIV status is monitored by expression of clinical symptoms as well as
      CD4 lymphocyte counts. The purpose of this study is to assess the relationship
      between delayed dental eruption (DDE) and the progression of pediatric HIV
      infection to AIDS. METHODS: A population of 70 perinatally HIV-infected children,
      aged 5 months to 13 years at their time of entry into the study, received dental
      examinations. Regression analysis between dental age and chronological age was
      performed. Subject CDC classification, adjusted for age, was used to determine an
      association between eruptive delay and severity of disease progression. RESULTS:
      Data revealed no significant difference in timing of eruption based on severity
      of CD4 depletion alone (P = 0.09). However, clinical symptom status was strongly
      associated with DDE (P = 0.003). The relationship between symptoms and DDE
      persisted after controlling for CD4 depletion. CONCLUSIONS: Our study indicates
      that there is a correlation between the progression from HIV infection to
      Pediatric AIDS and DDE and that this delay is most closely linked to severity of
      symptoms and not CD4 depletion.

PMID- 11447962
TI  - A survey of local and topical anesthesia use by pediatric dentists in the United
      States.
AB  - PURPOSE: The purpose of this survey is to evaluate current usage of local and
      topical anesthesia by Pediatric Dentist to evaluate the current practices.
      METHODS: Surveys were sent to 3051 pediatric dentists asking about types of
      anesthetics, considerations in determining local anesthetic dosage, time used to
      inject a cartridge and shortcomings of topical preparations. Data were computed
      for percentage responses. RESULTS: The response rate was 55%. Only 49% used exact
      body weight to determine local anesthetic dosage. The mostly commonly used
      needles for infiltrations were 30-gauge short and blocks were 27-gauge short.
      Only 11% of the respondents were using > or = 60 seconds to inject a full
      cartridge. Topical anesthetics were used by most, with the most commonly used
      brand being Hurricaine [correction of Hurricane]. A third waited 60 seconds
      before injecting after the application of the topical anesthetic. Most patients
      (89%) disliked the taste of topical anesthetics and adverse drug reactions were
      rarely seen. CONCLUSIONS: The findings of this study demonstrate that Pediatric
      Dentists are most commonly using Lidocaine as the preferred type of local
      anesthetic using 30 gauge short needle for infiltrations and 27 gauge short
      needle for blocks. Most were taking anywhere from 11-> 60 seconds to inject a
      cartridge. Topical anesthetic was used by most and the preferred brand was
      Hurricaine, however their perception of the effectiveness of topical anesthetics
      varied. There also appears to be a need to develop newer and better mode of
      topical anesthetic delivery system in the pediatric dental population.

PMID- 11447964
TI  - [13th spring meeting of the Japanese Society of Allergology. Yokohama,  Japan.
      May 10-12, 2001. Abstracts].

PMID- 11447963
TI  - Association of American Medical Colleges 39th Annual Research in Medical
      Education conference.

PMID- 11447965
TI  - [Regional meeting of the Japanese Circulation Society. Japan. 2000. Abstracts].

PMID- 11447966
TI  - [The 44th annual meeting of the Japanese Society of Nephrology. Tokyo,  Japan.
      May 27-29, 2001. Abstracts].

PMID- 11447967
TI  - (International Team for Oral Implantology) ITI Consensus Conference. Vitznau,
      Switzerland, 1997. Proceedings.

PMID- 11447968
TI  - Karl Heinrich Slotta (1895-1987) biochemist: snakes, pregnancy and coffee.
AB  - In 1923 Karl H. Slotta obtained his PhD in chemistry from the University of
      Breslau, Germany, where he continued to work. At the instigation of the
      gynaecologist Ludwig Fraenkel, Slotta made the first isolation of progesterone in
      1933. In 1934 he proposed the correct structural formula. Slotta was appointed
      professor of chemistry in 1935, but with the oppression of the Nazi regime
      mounting, he soon left Germany with his family to take a post at the Instituto
      Butantan, Brazil. Initially he worked on the chemistry of coffee. In 1938 Slotta
      and his brother-in-law Heinz Fraenkel-Conrat isolated crotoxin from Crotalus
      durissus terrificus venom, the first snake toxin to be obtained in crystalline
      form. They had evidence to suggest that the toxicity of crotoxin was due to a
      phospholipolytic action on nerve lipids. In 1938 Slotta's department was closed;
      he subsequently cofounded a biopharmaceutical company. In 1956 Slotta was
      appointed research professor of biochemistry at the University of Miami, USA.
      Slotta purified the most basic polypeptide from Naja naja venom, known as direct
      lytic factor, and with James Vick identified this as cardiotoxin. Karl H. Slotta
      will be remembered not only for his skill as a biochemist but also for his
      indomitable and cheerful spirit.

PMID- 11447969
TI  - Antimicrobial resistance surveillance of bacteria in 1999 in Korea with a special
      reference to resistance of enterococci to vancomycin and gram-negative bacilli to
      third generation cephalosporin, imipenem, and fluoroquinolone.
AB  - The trend of antimicrobial resistance of bacteria isolated from patients in 30
      Korean hospitals in 1999 was analyzed with a particular attention to cefotaxime-
      or fluoroquinolone-resistant gram-negative bacilli, imipenem-resistant
      Pseudomonas aeruginosa, and vancomycin-resistant enterococci. Adequacy of
      susceptibility testing, and any change in the frequencies of isolated species
      were also analyzed. The results showed that only 20% and 30% of hospitals tested
      the piperacillin-tazobactam and cefoxitin susceptibility of Enterobacteriaceae,
      respectively, only 24% of hospitals the piperacillin-tazobactam susceptibility of
      P. aeruginosa, and 17% of hospitals the fusidic acid susceptibility of
      staphylococci. Among the isolates 26.3% were glucose-nonfermenting gram-negative
      bacilli, and 34.7% of Enterococcus were Enterococcus faecium. Slight decline of
      cefotaxime-resistance rate to 20% was noted in Klebsiella pneumoniae, while
      fluoroquinolone-resistance rate was 68% in Acinetobacter baumannii. The
      ceftazidime- and imipenem-resistance rates were 17% and 18%, respectively in P.
      aeruginosa. The vancomycin-resistance rate of E. faecium rose significantly to
      15.1%, but the rates varied significantly depending on hospitals suggesting
      presence of different degree of selective pressure or nosocomial spread. In
      conclusion, the prevalence of imipenem-resistant P. aeruginosa and the increase
      of vancomycin-resistant E. faecium were the particularly worrisome phenomena
      observed in this study.

PMID- 11447970
TI  - When the map becomes the territory.

PMID- 11447971
TI  - Use of Dr is perhaps even more confusing in Germany than UK.

PMID- 11447983
TI  - Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment
      of bleeding peptic ulcers.

PMID- 11447984
TI  - Endosonographic assessment of multimodality therapy predicts survival of
      oesophageal carcinoma patients.

PMID- 11447985
TI  - Detection of upper GI cancer in patients taking antisecretory therapy prior to
      gastroscopy.

PMID- 11447986
TI  - Iatrogenic anxiety disorder related to failure of implantable defibrillator.

PMID- 11447987
TI  - Rapid response to low dose citalopram in pathological crying.

PMID- 11447989
TI  - [Regional meeting of the Japanese Society of Otolaryngology. Japan.  2001.
      Abstracts].

PMID- 11447988
TI  - Interferon-alpha-induced mood disorder with manic features.

PMID- 11447990
TI  - [43rd annual meeting of the Japan Geriatrics Society. Osaka, Japan. June 13-15,
      2001. Abstracts].

PMID- 11447992
TI  - Bibliography of journal articles (January to June 2000).

PMID- 11447991
TI  - 48th annual meeting of Japanese Association for Laboratory Animal Science.
      Yokohama, Japan. May 8-12, 2001. Abstracts.

PMID- 11447993
TI  - Heads up on adolescent health care.

PMID- 11447994
TI  - Apoptosis in the in vivo mammalian forebrain.
AB  - Apoptosis is a word originally introduced by Kerr, Wyllie, and colleagues for a
      cell death process they defined in terms of its ultrastructural appearance in
      nonneuronal cells from various tissues. There are very few studies providing
      detailed ultrastructural criteria for recognizing neuronal apoptosis in the in
      vivo mammalian brain. In the absence of such criteria, the Kerr/Wyllie
      description pertaining to nonneuronal cells has served as a reference standard.
      However, contemporary neurobiologists typically rely on cell culture models for
      studying neuronal apoptosis, and these models are rarely validated
      ultrastructurally; rather they are assumed to be appropriate models based on
      unvalidated biochemical tests for apoptosis. Relying on evidence generated in
      such cell culture models or on nonspecific cytochemical tests applied to brain
      tissue, many authors have recently suggested that an apoptotic mechanism may
      mediate neuronal death in a wide variety of human neurodegenerative diseases.
      Whether the cell death process in neurodegenerative diseases meets
      ultrastructural criteria for apoptosis has been given very little consideration.
      Recently, several methods have been described for triggering extensive apoptotic
      neurodegeneration in the developing in vivo mammalian brain. These methods
      include head trauma or treatment with several types of drugs (NMDA antagonists,
      GABAA agonists, or ethanol). We have performed an ultrastructural analysis of the
      neuronal cell death process triggered in the cerebral cortex and thalamus by
      these several methods and compared it with physiological cell death (PCD), a
      prototypic example of neuronal apoptosis that occurs naturally in the developing
      brain. Our findings, which are reviewed herein, demonstrate that the types and
      sequence of changes induced by each of the above methods are identical to those
      that characterize PCD. This confirms that each of these methods produces bona
      fide in vivo apoptotic neurodegeneration, and it signifies that our description
      of this neuronal apoptotic process, which differs in some respects from the
      Kerr/Wyllie description of nonneuronal apoptosis, can serve as a useful reference
      standard for recognizing the characteristic changes that in vivo neurons undergo
      when they are dying by an apoptotic mechanism.

PMID- 11447995
TI  - Oxidative cellular damage and the reduction of APE/Ref-1 expression after
      experimental traumatic brain injury.
AB  - The DNA repair enzyme, apurinic/apyrimidinic endonuclease (or redox effector
      factor-1, APE/Ref-1), is involved in base excision repair of
      apurinic/apyrimidinic sites after oxidative DNA damage. We investigated the
      expression of APE/Ref-1 and its relationship to oxidative stress after severe
      traumatic brain injury produced by controlled cortical impact in normal mice, and
      in mice over- or underexpressing copper-zinc superoxide dismutase (SOD1TG and
      SOD1KO, respectively). Oxygen free radical-mediated cellular injury was
      visualized with 8-hydroxyguanine immunoreactivity as a marker for DNA oxidation,
      and in situ hydroethidine oxidation as a marker for superoxide production. After
      trauma there was a reduced expression of APE/Ref-1 in the ipsilateral cortex and
      hippocampus that correlated with the gene dosage levels of cytosolic superoxide
      dismutase. The decrease in APE/Ref-1 expression preceded DNA fragmentation. There
      was also a close correlation between APE/Ref-1 protein levels 4 h after trauma
      and the volume of the lesion 1 week after injury. Our data have demonstrated that
      reduction of APE/Ref-1 protein levels correlates closely with the level of
      oxidative stress after traumatic brain injury. We suggest that APE/Ref-1
      immunoreactivity is a sensitive marker for oxidative cellular injury.

PMID- 11447996
TI  - Creatine increase survival and delays motor symptoms in a transgenic animal model
      of Huntington's disease.
AB  - There is substantial evidence for bioenergetic defects in Huntington's disease
      (HD). Creatine administration increases brain phosphocreatine levels and it
      stabilizes the mitochondrial permeability transition. We examined the effects of
      creatine administration in a transgenic mouse model of HD produced by 82
      polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin (N171
      82Q). Dietary supplementation of 2% creatine significantly improved survival,
      slowed the development of motor symptoms, and delayed the onset of weight loss.
      Creatine lessened brain atrophy and the formation of intranuclear inclusions,
      attenuated reductions in striatal N-acetylaspartate as assessed by NMR
      spectroscopy, and delayed the development of hyperglycemia. These results are
      similar to those observed using dietary creatine supplementation in the R6/2
      transgenic mouse model of HD and provide further evidence that creatine may exert
      therapeutic effects in HD.

PMID- 11447997
TI  - Ductal carcinoma in-situ arising in mammary-like glands of the vulva.
AB  - Recently a variant of cutaneous glands has been recognized in the anogenital
      region that combines the morphologic and immunohistochemical features of eccrine,
      apocrine, and mammary glands, so-called 'mammary-like glands of the vulva'.
      Carcinoma arising in mammary-like tissue of the vulva is a rare occurrence. So
      far, there have been 11 cases of primary, mammary-type invasive carcinoma and one
      case of in-situ carcinoma reported in the vulva. We describe an unusual case of
      ductal carcinoma in-situ without invasion arising in mammary-like glands of the
      vulva. A 57-year old woman presented with a 1-year history of a 1 cm nodule in
      the right labium majus. Excision showed ductal carcinoma in-situ with cribriform
      and papillary morphology in an adenosis-like lesion associated with mammary-like
      glands. No invasion into the stroma was identified. Immunostains were positive
      for gross cystic disease fluid protein 15 (GCDFP-15) and estrogen and
      progesterone receptors. An extensive survey including bilateral mammograms was
      negative. One year postoperatively, the patient shows no evidence of disease. To
      our knowledge, this represents the second case of DCIS associated with mammary
      like glands of the vulva reported in the English literature.

PMID- 11447998
TI  - Sulphur in the Arctic environment (1): results of a catchment-based multi-medium
      study.
AB  - S-concentrations were determined in 9 different sample materials (precipitation
      (rain and snow), vegetation, O-, E-, B- and C- horizon pf podzols, streams water
      and ground water) collected in eight small catchments (10-30 km2) at different
      distances from major SO2 point-source emitters on the Kola Peninsula, Russia.
      Comparison of the results from these materials, representing different
      compartments of the ecosystems under varying natural conditions leads to a better
      understanding of sources, cycling and fate of S in the Arctic environment. More
      than 300,000 t of   SO2 emitted annually from the Kola smelters affect the air
      quality over a large area. Arctic climatic conditions (cold and dry) and the
      remote location of the emitters results in considerably lower S-deposition values
      than those observed in central Europe. The pathways of atmospheric S-deposition
      in the terrestrial environment vary significantly from summer to winter because
      different compartments of the ecosystems, with a different capability to
      accumulate S, are active. The actual S-flux is altered by every component of the
      ecosystem. When estimating the total S-deposition this effect must be considered.

PMID- 11447999
TI  - Top CDC official for HIV to advise Gates Foundation.

PMID- 11448000
TI  - Surveillance shows success of perinatal HIV prevention guidelines.

PMID- 11448001
TI  - Plasma ascorbic acid and risk of heart disease and cancer.

PMID- 11448002
TI  - Replacement of liver venous endothelium.

PMID- 11448003
TI  - Cat allergen and sensitisation.

PMID- 11448004
TI  - Cushing's syndrome.

PMID- 11448005
TI  - Pseudoexfoliation and aortic aneurysms.

PMID- 11448006
TI  - Preventing toxaemia.

PMID- 11448007
TI  - Rethinking the approach to abdominal aortic aneurysms.

PMID- 11448009
TI  - Observational studies for intervention assessment.

PMID- 11448008
TI  - Antiflu, or antideath vaccination?

PMID- 11448011
TI  - Role of K vitamins in the regulation of tissue calcification.

PMID- 11448012
TI  - Parathyroid hormone increases the expression level of matrix metalloproteinase-13
      in vivo.
AB  - Parathyroid hormone (PTH) increases serum calcium (Ca) by enhancing bone
      resorption and renal Ca reabsorption. However, detailed mechanisms of enhanced
      bone resorption by PTH remain to be elucidated. Although PTH has been shown to
      increase the expression level of osteoblastic matrix metalloproteinase (MMP)-13
      in vitro, only limited results are available regarding the in vivo regulation of
      MMP expression. In the present study, we have examined expression levels of MMPs
      in PTH-infused rats. Infusion of 1.5 or 2.0 nmol/kg/day rat PTH(1-34) for 3 days
      resulted in a dose-dependent increase in serum Ca. PTH infusion also decreased
      serum phosphate levels and increased urinary excretion of Ca and phosphate.
      Infusion of PTH for 7 days resulted in less severe hypercalcemia and
      hypophosphatemia. Urinary Ca and phosphate excretion in rats infused for 7 days
      was less than that in rats infused for 3 days. Northern blot analysis showed that
      PTH infusion increased the expression level of MMP-13 in calvaria, although it
      did not affect MMP-2 expression. Furthermore, the time-course and severity of
      hypercalcemia and hypercalciuria correlated with the expression level of MMP-13.
      In situ hybridization also showed that PTH infusion increased the expression
      level of MMP-13 in femora. These results indicate that PTH enhances MMP-13
      expression in vivo and suggest that PTH stimulates bone resorption at least
      partly by enhancing MMP-13 expression.

PMID- 11448013
TI  - Transient suppression of core-binding factor alpha 1 expression by basic
      fibroblast growth factor in rat osteoblast-like osteosarcoma ROS17/2.8 cells.
AB  - Core-binding factor alpha 1 (Cbfa1) is considered a prerequisite transcription
      factor for osteoblastic differentiation, based on experiments performed in knock
      out mice. Cbfa1 binding sequences have been located in the promoter regions of
      various osteoblast phenotype-related genes, which are also known to be regulated
      by fibroblast growth factor (FGF). To elucidate the molecular mechanisms of FGF
      regulation of osteoblasts, we investigated the effects of FGF on Cbfa1 expression
      in osteoblast-like cells. We found that basic FGF, at 10 ng/ml, suppressed Cbfa1
      mRNA expression in ROS17/2.8 cells. To detect the two distinct mRNA species that
      give rise to Pebp2alphaA/Cbfa1 and Osf2/Til-1/Cbfa1, we used semi-quantitative
      reverse transcription-polymerase chain reaction analysis using specific sets of
      primers. This analysis indicated that treatment with FGF transiently decreased
      the abundance of only the Osf2/Til-1/Cbfa1 isoform and not the Pebp2alphaA/Cbfa1
      isoform in ROS17/2.8 cells. The suppression of Osf2/Til-1/Cbfa1 was time
      dependent and was observed up until 48h, and Cbfa1 mRNA levels then returned
      closer to control levels. Dose-dependent suppression by FGF was observed only
      with regard to mRNA levels of Osf2/Til-1/Cbfa1 and not for Pebp2alphaA/Cbfa1
      mRNA. These data indicate that FGF suppresses Cbfa1 mRNA expression and that the
      Osf2/Til-1/Cbfa1 isoform is the specific target of FGF regulation in osteoblastic
      osteosarcoma ROS17/2.8 cells.

PMID- 11448014
TI  - Establishment and characterization of macrophage-like cell lines expressing
      osteoclast-specific markers.
AB  - Osteoclasts differentiate from hematopoietic precursors of the
      monocyte/macrophage lineage to mononuclear preosteoclasts and multinuclear mature
      osteoclasts. In the present study, we report on the establishment of macrophage
      like cell lines from mouse bone marrow by coculturing bone marrow cells with
      mouse chondrocytes. Isolated clones (MLC-6 and MLC-7 cells) expressed fully
      differentiated osteoclast markers, such as calcitonin receptors, vitronectin
      receptors, tartrate-resistant acid phosphatase and vacuolar H+ -ATPase, in the
      absence of osteoclast differentiation factor/osteoprotegerin ligand/RANKL/TRANCE,
      which was essential for osteoclast differentiation. Most clones also maintained
      expression of a macrophage-associated protein, namely non-specific esterase. Both
      MLC-6 and MLC-7 cells released cathepsin K into the culture medium. Both clones
      resolved dentine slices when cocultured with the osteoblast cell line ST2. The
      cloned cell lines are considered to be useful tools in the study of osteoclast
      differentiation.

PMID- 11448015
TI  - Sequential changes in transforming growth factor (TGF)-beta1 concentration in
      synovial fluid and mRNA expression of TGF-beta1 receptors in chondrocytes after
      immobilization of rabbit knees.
AB  - We have previously reported that a combination of transforming growth factor
      (TGF)-beta1 and basic fibroblast growth factor (bFGF) synergistically increases
      the proliferation of chondrocytes obtained from knee joint immobilized for 7-14
      days in male Japanese white rabbits. In the present study, we performed
      experiments with chondrocytes and syn ovial fluid obtained from rabbit knees
      immobilized for 0-42 days, to clarify the sequential changes in TGF-beta1 and
      bFGF concentrations in synovial fluid and the mRNA expression of TGF-beta1
      receptor type I (RI) and II (RII) in chondrocytes after immobilization. The
      combination of TGF-beta1 and bFGF had a synergistic effect on the proliferation
      of chondrocytes obtained from knee joints immobilized for 7-14 days. The
      concentration of TGF-beta1 in synovial fluid was significantly higher (up to 3.6
      fold) at 7-28 days after immobilization compared with that at 2 days. The mRNA
      for RI and RII was expressed during the whole immobilization period. The con
      centration of bFGF was kept at the same level at 2-7 days after immobilization,
      and gradually decreased thereafter. In the early stages of degenerated cartilage,
      up to 14 days after immobilization, the concentrations of both TGF-beta1 and bFGF
      were higher in the synovial fluid and mRNA expression of TGF-beta1 receptors in
      chondrocytes was kept.

PMID- 11448016
TI  - Immunoblot detection and expression of enamel proteins at the apical portion of
      the forming root in porcine permanent incisor tooth germs.
AB  - There have been many immunohistochemical studies of enamel proteins during root
      formation. In the present article, the detection and expression of enamel
      proteins in tissue samples prepared from the apical portion of the forming root
      (APFR) in porcine permanent incisor tooth germs were studied. Amelogenin,
      enamelin, and sheathlin were detected by immunoblot analysis, but only in small
      amounts. The detection of their derivatives indicated their degradation. It is,
      at present, unclear as to which proteinases are involved in these degradations,
      because activity of enamel matrix serine proteinase 1 and enamelysin was not
      detected on gelatin and casein zymograms. The expression of enamel proteins was
      also proved in the APFR sample by the detection of polymerase chain reaction
      products of their cDNAs, and this may be related to cells of fragmentized
      Hertwig's epithelial root sheath. Amelogenin expression was not greater than that
      of enamelin and sheathlin. It was different from the expression pattern of
      secretory ameloblasts involved in enamel matrix formation. These results suggest
      that the amelogenins found in the APFR do not form a three-dimensional structure
      of amelogenin micelles, which has been proposed for the secretory enamel matrix
      structure. In this case, the enamel proteins could spread out easily following
      degradation into the matrix of future cementum. Some of their derivatives may
      play a role in the formation of the cementum.

PMID- 11448017
TI  - Effect of parathyroid hormone on cortical bone response to in vivo external
      loading of the rat tibia.
AB  - Cortical bone responses following administration of parathyroid hormone (PTH)
      were evaluated using a four-point bending device to clarify the relationship
      between the effect of PTH and mechanical loading. Female Wistar rats, 6-months
      old, [corrected] were used. Rats were randomized into three groups (n =
      10/group), namely PTH-5 (5 microgram PTH/kg body weight), PTH-30 (30 microgram
      PTH/kg body weight), and PTH-v (vehicle). PTH (human PTH (1-34)) was injected
      subcutaneously three times/week for 3 weeks. Loads on the right tibia were
      applied in vivo at 29.1 +/- 0.3 N for 36 cycles at 2 Hz 3 days/week for 3 weeks
      using four-point bending. The administration of PTH and tibial mechanical loading
      were performed on the same day. After calcein double labeling, rats were killed
      and tibial cross-sections were prepared from the region with maximal bending at
      the central diaphysis. Histomorphometry was performed over the entire periosteal
      and endocortical surfaces of the tibiae, dividing the periosteum into lateral and
      medial surfaces. The in vivo average peak tibial strains (predicted) on the
      lateral periosteal surface were 1392.4, 1421.8 and 1384.7 (mu)strain in PTH-v,
      PTH-5 and PTH-30 groups, respectively, showing no significant difference among
      the three groups. Significant loading-related increases in the bone formation
      surface, mineral apposition rate, and bone formation rate were observed at the
      periosteal and endocortical surfaces. Significant differences between PTH groups
      were also seen. Interaction between mechanical loading and PTH was significant at
      both periosteal and endocortical surfaces. It is concluded that PTH has a
      synergistic effect on the cortical bone response to mechanical loading.

PMID- 11448018
TI  - Analgesic effect of etidronate on degenerative joint disease.
AB  - In the present study, 80 patients with degenerative joint disease, spondylosis
      deformans, and/or osteoarthritis of the knee with back or joint pain, especially
      on movement and strain, were randomly divided into four groups. Group A received
      no etidronate, while groups B, C and D received 66, 133 and 200 mg/day
      etidronate, respectively, for 12 months. Every 3 months, after evaluating
      subjective pain on a visual rating scale (VRS), skin impedance was measured with
      subjects in a quiet sitting position and with the application of various strains
      on the spine and knee, including standing up from quiet sitting on a chair,
      bending forward to flex the spine, squatting to flex the knee, walking 20 paces
      on a flat floor, ascending 10 stair steps and descending 10 stair steps. A dose
      related improvement of subjective pain on the VRS with a parallel decrease in the
      percentage fall in skin impedance was noted. The intra-individual coefficients of
      variation (CV) of L1-L4 bone mineral density (BMD) on dual-energy X-ray
      absorptiometry were calculated as a possible index for spondylotic changes before
      and after treatment as an indication of spondylotic deformity, because no
      established method is yet available to evaluate such changes objectively. A dose
      related decrease in CV of BMD was also noted, parallel to the analgesic effect.

PMID- 11448019
TI  - Relationship between bone mineral density and insulin resistance in polycystic
      ovary syndrome.
AB  - The aim of the present study was to evaluate whether there is a relationship
      between bone mineral density (BMD) and insulin resistance and hyperinsulinemia in
      women with polycystic ovary syndrome (PCOS). The study consisted of 28
      amenorrheic women with PCOS and 11 amenorrheic women without PCOS. Fifteen
      healthy women with normal ovulatory function, matched for age and body mass index
      (BMI), served as controls. BMD was measured at the lumbar spine and left femoral
      neck with dual-energy X-ray absorptiometry. Blood samples were obtained to
      measure serum levels of insulin, follicle-stimulating hormone, luteinizing
      hormone, sex hormone-binding globulin (SHBG), total and free testosterone,
      androstenedione and estradiol by radioimmunassay. Insulin resistance was
      estimated by the in sulin tolerance test (ITT), and K(ITT) was taken as the
      insulin sensitivity index. In the PCOS group, K(ITT) was significantly lower and
      insulin levels were higher than in either of the control groups (P < 0.001). BMD
      in the PCOS group was lower than in the healthy group and higher than in the
      amenorrheic control group (P < 0.05). In the PCOS group, there were positive
      correlations of BMD of the lumbar spine with insulin (r = 0.42: P < 0.05) and
      negative correlations of BMD with K(ITT) (r = -0.58; P < 0.001) and SHBG (r = 
      0.38; P < 0.05). The inverse association of BMD and K(ITT) was independent of
      BMI, insulin, SHBG, androstenedione, and free testosterone. In conclusion,
      insulin resistance and hyperinsulinemia in women with PCOS may be a relative
      protective factor against bone mineral loss.

PMID- 11448020
TI  - Identification of a novel frameshift mutation (383insT) in the RUNX2 (PEBP2
      alpha/CBFA1/AML3) gene in a Japanese patient with cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant disorder due to mutations
      in runt-related gene 2 (RUNX2)/polyomavirus enhancer-binding protein 2alphaA
      (PEBP2alphaA)/core-binding factor A1 (CBFA1)/acute myeloid leukemia 3 (AML3). To
      investigate the RUNX2 mutations in a Japanese patient with classic CCD, we
      analyzed the RUNX2 gene using polymerase chain reaction (PCR)-single-strand
      conformation polymorphism and PCR-restriction fragment length polymorphism. The
      patient had hypoplasia of the clavicles, patent fontanelles, short stature,
      supernumerary teeth, and retention of deciduous dentition. We identified a 1-bp
      insertion (383insT) at codon 128 of the RUNX2 gene. The 383T insertion affects
      the conserved residue in the runt domain and results in premature termination in
      the runt domain.

PMID- 11448021
TI  - Phenotypic recombination between bean common mosaic and bean common mosaic
      necrosis potyviruses in vivo.
AB  - The US-5 strain of bean common mosaic virus (BCMV) and the NL-8 strain of bean
      common mosaic necrosis virus (BCMNV) are both seedborne potyviruses in common
      bean (Phaseolus vulgaris L). They have contrasting and highly stable biological
      characteristics which are genetically controlled. BCMV strain US-5 belongs to
      pathogenicity group IV. BCMNV strain NL-8 belongs to pathogenicity group III. The
      two strains have contrasting serological characteristics: NL-8 is serotype A; US
      5 is serotype B. When these two strains were maintained separately or as a
      mixture for more than three years (39 serial transfers) or in more than 100
      plants of either of two susceptible hosts, we were unable to isolate a single
      virus strain that exhibited mutant-like or recombinant-like characteristics.
      However, within 28 days (during the 1st passage) after these 2 strains were
      inoculated to opposite primary leaves of bean plants that were susceptible to one
      virus and resistant to the other, we were able to recover 17 strains that clearly
      possessed recombinations of various phenotypic characteristics from each of the
      two "parental" viruses. Three types of phenotypic characteristics were recombined
      singly or in combination during a single passage in vivo: 1) Biological
      characteristics known to be controlled by genes for pathogenicity; 2) Serotype;
      and 3) Temperature-induced hypersensitive vascular necrosis. Each of the
      phenotypic recombinant strains contained only pathogenicity genes or serological
      characteristics found in one or both parents. In no case did we isolate a strain
      that could be described as a random mutation or one that contained pathogenicity
      or serological characteristics which were not found in at least one parent
      strain. This is the first known demonstration of phenotypic recombinations
      between distinct potyviruses in vivo. Implications for the evolution of new virus
      strains through the use of resistant cultivars and its impact on breeding
      programs and bean seed production are discussed.

PMID- 11448022
TI  - Phylogenetic analysis of the L and HN gene of ophidian paramyxoviruses. Brief
      report.
AB  - Two reptilian paramyxoviruses, isolated from a neotropical rattlesnake
      (neotropical virus, NTV, ATCC VR-1408) and a bush viper (bush viper virus, BVV,
      ATCC VR- 1409), respectively, were analysed to determine their taxonomic position
      among other reptilian paramyxoviruses investigated previously by Ahne et al.. A
      679 bp long region of the hemagglutinin-neuraminidase (HN) gene and a 627 bp long
      region of the large (L) gene were reverse transcribed, amplified by polymerase
      chain reaction (PCR), and sequenced. The deduced amino acid sequences were
      compared to mammalian paramyxoviruses belonging to the genera Respirovirus and
      Rubulavirus. The deduced amino acid sequences revealed 58.9 to 62% homology for
      the partial L protein and 41% to 47.1% homology for the partial HN protein. For
      phylogenetic analyses, a 518 bp L gene and a 352 bp HN gene fragment were used,
      both generating similar trees consisting of two distinct main groups, and some
      intermediate isolates. BVV clustered within group "b" while NTV clustered
      together with the intermediate ophidian paramyxovirus isolate Crot2-OH90.

PMID- 11448023
TI  - Phylogenetic relationships of bovine immunodeficiency virus in cattle and
      buffaloes based on surface envelope gene sequences. Brief report.
AB  - Isolates of bovine immunodeficiency virus (BIV) exhibit a striking genomic
      diversity, most of which are located in the viral envelope gene. Since this
      property of the BIV group of viruses may play an important role in the
      pathobiology of the virus, the surface envelope gene, particularly the conserved
      (C) 2, hypervariable (V) 1, V2 and C3 regions, of eleven different isolates from
      different environments with different bovine breeds naturally infected with BIV,
      including dairy cows in Japan, buffaloes in Pakistan and draught animals in
      Cambodia, were sequenced. When compared to the nucleotide sequence of American
      BIV isolates, all Asian BIV field isolates seem to be smaller, several base
      substitutions were observed in the V1 region, and deletions were also found in
      the V2 region of env gene in these samples. However, deduced amino acid sequences
      were not so different among isolates from different bovine breeds, suggesting
      that bovine susceptibility to BIV infection may not depend upon bovine breed or
      buffaloes. Moreover, phylogenetic analysis revealed that genotypes were distinct
      between Asian and American BIV isolates and these results also provide an
      information on the molecular epidemiology of naturally occurring BIV infection in
      cattle and buffaloes.

PMID- 11448024
TI  - In memoriam Pekka Eljas Halonen (1927-2001).

PMID- 11448025
TI  - Frequency of morphological phage descriptions in the year 2000. Brief review.
AB  - Over 5100 bacterial viruses have been examined in the electron microscope since
      1959. About 4950 phages (96%) are tailed and only 186 phages (3.6%), are cubic,
      filamentous, or pleomorphic. Phages belong to 13 virus families and occur in over
      140 bacterial genera. Phages are listed by morphotypes and host genera.
      Siphoviridae or phages with long, noncontractile tails comprise 61% of tailed
      phages. The distribution of phages in different bacterial phylogenetic divisions
      is shown.

PMID- 11448026
TI  - Comparative analysis of host responses related to immunosuppression between
      measles patients and vaccine recipients with live attenuated measles vaccines.
AB  - Measles virus infection induces a profound immunosuppression. We analyzed in a
      time-dependent manner peripheral bloods of one to two-year-old children immunized
      with live attenuated measles vaccines, compared with age-matched measles
      patients, for immunosuppression. In contrast to transient severe lymphopenia with
      measles patients, primarily due to extensive apoptosis of a broad spectrum of
      uninfected lymphocytes, neither apoptosis nor lymphopenia occurred with measles
      vaccine recipients. Increase in number and activation of NK cells, which might
      compensate for the lymphopenia in measles patients, were not found with the
      vaccinees. While cell surface expression of apoptosis-related molecules such as
      TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-receptors, CD95(Fas) and Fas
      ligand, and plasma interferon-gamma were increased for measles patients, they
      remained unchanged after vaccination. Plasma interleukin (IL)-18, which is
      responsible for inducing apoptosis in several infectious diseases, was increased
      predominantly with measles patients, whereas the increase remained marginal with
      the vaccinees. IL-10 was elevated transiently in both measles patients and
      vaccinees. Decrease in plasma IL-12, which is often correlated with T cell
      suppression, was not found for both cases. Serum IgM and IgG antibodies to
      measles virus were induced at lower titers in the vaccinees than measles
      patients. These results indicate that in contrast to wild-type measles virus,
      live measles vaccines hardly provoked host cytokine responses that lead to
      apoptotic cytolysis of uninfected lymphocytes, lymphopenia and immunosuppression,
      and thereby induced weaker immune responses to the virus.

PMID- 11448027
TI  - Recombinant proteins produced by vaccinia virus vectors can be incorporated
      within the virion (IMV form) into different compartments.
AB  - Vaccinia virus (VV) is one of the largest and most complex of animal viruses,
      with a virion that contains about 100 different polypeptides. Assembly of the
      viral proteins occurs in discrete cytoplasmic sites leading to formation of two
      infectious forms, an abundant (>90%) intracellular mature virus (IMV) with an
      envelope, and a minor extracellular enveloped virus (EEV) with an extra membrane
      acquired from the trans-Golgi network. It has been shown that while EEV contains
      in the outer membrane cellular proteins probably acquired during virus release
      from cells, however, IMV exclude host proteins during assembly. Since VV
      recombinants (VVr) expressing genes of interest are candidates as potential
      vaccines against pathogens and cancer, it becomes important to know if VVr can
      acquire foreign proteins during morphogenesis. In this investigation we show that
      purified virions (IMVs) from VVr can incorporate foreign proteins into different
      sites in the virus particle. By sequential fractionation of virion compartments
      with detergents, we found foreign proteins in the lipid envelope (cytokine IL-12
      and CS antigen of Plasmodium yoelii), as part of a protein matrix-like membrane
      (HIV-1 gp41 of env), or more closely associated with the core containing the DNA
      complexes (HIV-1 gp160; a multiepitopic protein with the V3 loop of HIV-1 Env
      from different isolates, and beta-galactosidase). Similar findings were observed
      with purified virions derived from the WR strain as well as from the highly
      attenuated modified vaccinia virus Ankara (MVA) strain. These observations should
      be taken into consideration when VVr are used in clinical trials or in other
      vaccination approaches.

PMID- 11448028
TI  - Attenuation of a field Sendai virus isolate through egg-passages is associated
      with an impediment of viral genome replication in mouse respiratory cells.
AB  - We investigated the mechanisms responsible for attenuation of mouse pathogenicity
      of Sendai virus (SeV) through passages in eggs. A highly virulent clone, E0,
      derived from the field SeV Hamamatsu strain, was successively passaged in hen's
      eggs. Analysis of the mouse lethal dose 50% (MLD50) of virus clones obtained from
      the viruses at egg-passages 1, 15, 30 and 50 demonstrated that attenuation of E0
      by egg-passage occurred due to the gradual appearance of and replacement by virus
      variants possessing higher MLD50. Comparison of viral replication in the mouse
      lung and mouse pathogenicity with the representative SeV clones, E0, E15c12,
      E30c12 and E50c19, obtained from the respective egg-passages revealed that the
      low pathogenicity of the egg-passaged clones was due to poor multi-cycle viral
      replication in the lung. Furthermore, MLD50s of the SeV clones were found to be
      negatively correlated with the replication capability in primary mouse pulmonary
      epithelial (MPE) cells; the egg-passaged clones with more attenuated phenotypes
      showed lower replication capability in MPE cells. In the MPE cells infected with
      the SeV clones at m.o.i. 10, however, viral protein and mRNA syntheses of the egg
      passaged clones were enhanced or comparable to those of the parental E0 clone at
      1 day and 2 days post infection (p.i.) but decreased more rapidly thereafter. In
      contrast, viral genome synthesis of the egg-passaged clones in the cells at 2
      days p.i. was several times lower than that of E0. These results strongly suggest
      that attenuation of a virulent field SeV strain by egg-passage occurs due to the
      appearance and selection of virus variants possessing poor propagation capacity
      in mouse respiratory epithelial cells, which is caused primarily by an impediment
      of viral genome replication.

PMID- 11448029
TI  - Production, characterisation and applications of monoclonal antibodies to porcine
      circovirus 2.
AB  - The production, preliminary characterisation and applications of monoclonal
      antibodies (mabs) against six porcine circovirus 2 isolates are described. A
      total of 14 stable hybridomas were produced, of which 7 were characterised. All
      of the mabs characterised were of IgG isotype. All the mabs tested reacted by IIF
      with acetone-fixed cell cultures infected with PCV2 isolates from Canada, France,
      Spain, Denmark, USA and UK. No cross-reactivity with a porcine circovirus 1 field
      isolate was demonstrated using the panel of mabs tested. In addition, one of the
      seven mabs tested demonstrated neutralising activity against PCV2 isolates from
      Canada and France. The use of selected PCV2-specific mabs for the development of
      virus detection methodologies is described.

PMID- 11448030
TI  - Engineering of alfalfa mosaic virus RNA 3 into an expression vector.
AB  - RNA 3 of alfalfa mosaic virus (AMV) encodes the 5'-proximal movement protein (MP)
      gene and the 3'-proximal coat protein (CP) gene which is expressed from a
      subgenomic RNA. Several strategies were explored to use this RNA as a vector for
      expression of the green fluorescent protein (GFP) in Nicotiana tabaccum plants
      expressing the viral polymerase proteins P1 and P2 (P12 plants). Insertion of a
      subgenomic promoter (sgp)-GFP cassette between the CP gene and the 3'
      untranslated region (UTR) interfered with RNA accumulation in protoplasts,
      indicating that cis-acting sequences required for replication were disrupted.
      When GFP was fused to the N-terminus of MP or CP, the chimeric RNAs accumulated
      in protoplasts but cell-to-cell movement in plants was blocked. Insertion of a
      GFP-sgp cassette immediately upstream of the CP gene caused a hypersensitive host
      response. However, insertion of a GFP-sgp cassette upstream of the MP gene did
      not affect symptom formation and yielded a vector that expressed GFP in
      inoculated but not in the systemic leaves of both P12 tobacco and non-transgenic
      N. benthamina plants. When the size of the GFP gene was reduced from 700 to 300
      nucleotides, virus infection was observed in the non-inoculated leaves. Analysis
      of the progeny of some chimera revealed novel data on replication, encapsidation
      and recombination of AMV RNA 3.

PMID- 11448031
TI  - Nucleotide sequence of 3'-end of the genome of Taura syndrome virus of shrimp
      suggests that it is related to insect picornaviruses.
AB  - Taura syndrome disease, caused by Taura syndrome virus (TSV), is one of the most
      important viral diseases of penaeid shrimp in the Western Hemisphere resulting in
      catastrophic disease epidemics in farmed shrimp. We have cloned and sequenced a
      3278 bp cDNA representing the 3' end of the TSV genome. Sequence analyses
      revealed that frame + 2 had the longest open reading (ORF) frame. This frame
      contained a 5'-terminal 19 non-coding bases followed by an ORF from nucleotides
      20 to 3053 (encoding 1011 amino acids, aa) and a 3' untranslated region of 225
      nts. The deduced aa sequence of TSV showed significant similarities with those of
      the coat proteins of insect picornaviruses, Rhopalosiphum padi virus, Plautia
      stali intestine virus, Drosophila C virus, Triatoma virus of Triatoma infestans
      and Himetobi P virus of brown plant hopper. A single transcript of approximately
      10 kb was detected by Northern blot hybridization suggesting that the TSV coat
      protein gene is not expressed as a subgenomic RNA. We concluded that the genome
      organization of TSV is similar to insect picornaviruses. This is the first
      molecular evidence of occurrence of a picornavirus in the class Decapoda.

PMID- 11448032
TI  - Postbinding fusion function contributed by a chimeric murine leukemia virus
      envelope protein.
AB  - We previously obtained a chimeric Friend murine leukemia virus (FMLV) envelope
      protein (Env) in which the whole receptor-binding domain (RBD) was replaced with
      a surface domain of human CD4. Here, we examined if the postbinding fusion
      function of the CD4-Env chimera still remains to be intact. While a pseudotype
      MLV bearing CD4-Env showed no infectivity, NIH 3T3 cells could be infected with a
      pseudotype MLV bearing both CD4-Env and a mutant FMLV Env defective in
      postbinding fusion function. The pseudotype MLV showed no infectivity on HeLa
      cells but on the FMLV receptor (mCAT1)-expressing HeLa cells. In NIH 3T3 cells,
      the R-peptide-deleted CD4-Env could not induce syncytia by itself but did so in
      co-operation with the fusion-deficient Env. Syncytia induced by the coexpression
      were not observed in HeLa cells but in the mCAT1-expressing HeLa cells. These
      results indicate that the CD4-Env could contribute postbinding fusion function in
      the membrane fusion process triggered by FMLV RBD-mCAT1 interaction.

PMID- 11448033
TI  - Changes in the haemagglutinin and the neuraminidase genes prior to the emergence
      of highly pathogenic H7N1 avian influenza viruses in Italy.
AB  - Outbreaks of avian influenza due to an H7N1 virus of low pathogenicity occurred
      in domestic poultry in northern Italy from March 1999 until December 1999 when a
      highly pathogenic avian influenza (HPAI) virus emerged. Nucleotide sequences were
      determined for the HA1 and the stalk region of the neuraminidase (NA) for viruses
      from the outbreaks. The HPAI viruses have an unusual multibasic haemagglutinin
      (HA) cleavage site motif, PEIPKGSRVRRGLF. Phylogenetic analysis showed that the
      HPAI viruses arose from low pathogenicity viruses and that they are most closely
      related to a wild bird isolate, A/teal/Taiwan/98. Additional glycosylation sites
      were present at amino acid position 149 of the HA for two separate lineages, and
      at position 123 for all HPAI and some low pathogenicity viruses. Other viruses
      had no additional glycosylation sites. All viruses examined from the Italian
      outbreaks had a 22 amino acid deletion in the NA stalk that is not present in the
      N1 genes of the wild bird viruses examined. We conclude that the Italian HPAI
      viruses arose from low pathogenicity strains, and that a deletion in the NA stalk
      followed by the acquisition of additional glycosylation near the receptor binding
      site of HA1 may be an adaptation of H7 viruses to a new host species i.e.
      domestic poultry.

PMID- 11448034
TI  - Characterization of a new citrus viroid species tentatively termed Citrus viroid
      OS.
AB  - A new viroid was obtained from a viroid sample, named 'OS', collected from a
      citrus plant. The viroid consists of 330-331 nucleotides, contains the central
      conserved region (CCR) characteristic of the genus Apscaviroid, and has the
      highest sequence similarity (only 68%) with Citrus III viroid (CVd-III) among
      known viroids. This viroid, by itself, caused only mild petiole necrosis and
      characteristically very mild leaf bending in Arizona 861-S1 Etrog citrons (Citrus
      medica L.), the degree of which differed from that induced by other citrus
      viroids. This viroid could be a new citrus viroid species belonging to the genus
      Apscaviroid; for convenience, it was tentatively named Citrus viroid OS (CVd-OS)
      after the original sample. CVd-OS has chimeric features related to other viroids.
      In particular, CVd-OS has high sequence similarity with CVd-III and Apple dimple
      fruit viroid in the putative central and terminal left domains, including a
      duplicative sequence from the lower CCR of the genus Pospiviroid in the left
      terminus. Further, CVd-OS shares high sequence similarity with Citrus exocortis
      viroid (CEVd) in the lower strand of the putative variable and terminal right
      domains, including the sequence identical to that of the right termini of CEVd
      and of Citrus IV viroid.

PMID- 11448035
TI  - Glycoproteins H and L of Marek's disease virus form a hetero-oligomer essential
      for translocation and cell surface expression.
AB  - Glycoproteins H and L form a hetero-oligomeric complex (gH-L) which plays an
      important role in virus entry to host cells and cell-to-cell infection in
      herpesviruses. Interaction of gH and gL is considered to be critical for the
      biological function of these two glycoproteins. To investigate the interaction of
      MDV gH and gL, both gH and gL were expressed in in vitro cell culture systems
      using indirect immunofluorescence assay with gH and gL antibodies. The results
      suggested that co-expression of gH and gL in the same cells are required and
      necessary for both gH and gL subcellular translocation and cell surface
      expression. gL expressed in recombinant fowlpox virus (rFPV) infected chicken
      embryo fibroblasts (CEF) was consistently secreted into the culture medium. The
      primary peptide of gL binds with that of gH in the cytosol or ER lumen. By
      binding with gH, gL could anchor itself on the cell surface allowing for surface
      expression and viral spread to uninfected cells. The binding domain of gH was
      mapped to the amino acids 451-659 (SacI-HindIII) fragment and was essential for
      gH-L complex formation.

PMID- 11448036
TI  - Mucosal disease induced in cattle persistently infected with bovine viral
      diarrhea virus by antigenically different cytopathic virus.
AB  - Four cattle persistently infected with non-cytopathic (NCP) bovine viral diarrhea
      (BVD) virus were challenged with cytopathic (CP) BVD virus that was antigenically
      different from the persistent virus. Two of the animals were injected with
      dexamethasone (DM) and then challenged. They developed mucosal disease on days 21
      and 33 post-challenge. CP-BVD viruses were isolated from their lymph nodes but
      not from the sera. The isolates were antigenically different from the persistent
      virus and the nucleotide sequence of a 787 base region in the E2 gene was
      markedly different. One of the isolates was indistinguishable from the challenge
      virus by virus neutralization tests and the nucleotide sequence showed high
      homology with that of the challenge CP-BVD virus. The other two cattle,
      challenged with the CP-BVD virus without DM treatment, developed mucosal disease
      at 30 and 264 days post-inoculation. CP-BVD virus was isolated from the sera as
      well as the lymph nodes of the cattle and was antigenically and genetically
      similar to the persistent virus and different from the challenge CP-BVD virus.
      The present results indicate that cattle persistently infected with NCP-BVD virus
      can develop mucosal disease induced by antigenically different CP-BVD viruses
      when their cellular immunity is suppressed, although they are not immunotolerant
      to the virus.

PMID- 11448037
TI  - Key word: chromosome.
AB  - The word chromosome has survived for over 100 years, because it succinctly
      defines what early cytologists were able to see with the most modern instrument
      of their time, a light microscope. It was introduced in a review that became
      widely known and was published almost simultaneously in German, English and
      French (Waldeyer 1888, 1889, 1890a, 1890b). In the late 19th century, these three
      languages were in strong competition for international status as the idiom of
      science. At the same time, Greek was also considered as a candidate for a
      nationalistically neutral language of science, and it seems more than coincidence
      that the word [Greek letters: see text] matches well the coherent Greek
      terminology used to describe the cell cycle in mitosis as well as meiosis. Emil
      Heitz (1935) maintained--in the face of reactionary German efforts to replace the
      term--that in using "the ineradicable word chromosome we think last of all that
      it indicates a body, that stains intensely,". Significantly, the key word is no
      longer restricted to eukaryotes, but has been readily adopted by microbial
      geneticists (Heidelberg el al. 2000) and acknowledged as defining the elementary
      unit of genomic partition.

PMID- 11448038
TI  - Comparative genomic in situ hybridization (cGISH) analysis on plant chromosomes
      revealed by labelled Arabidopsis DNA.
AB  - A new approach for comparative cytogenetic banding analysis of plant chromosomes
      has been established. The comparative GISH (cGISH) technique is universally
      applicable to various complex genomes of Monocotyledonae (Triticum aestivum,
      Agropyron elongatum, Secale cereale, Hordeum vulgare, Allium cepa, Muscari
      armenaticum and Lilium longiflorum) and Dicotyledonae (Vicia faba, Beta vulgaris,
      Arabidopsis thaliana). Labelled total genomic DNA of A. thaliana generates
      signals at conserved chromosome regions. The nucleolus organizing regions (NORs)
      containing the majority of tandemly repeated rDNA sequences, N-band regions
      containing satellite DNA, conserved homologous sequences at telomeres and
      additional chromosome-characteristic markers were detected in heterologous FISH
      experiments. Multicolour FISH analysis with repetitive DNA probes simultaneously
      revealed the chromosome assignment of 56 cGISH signals in rye and 61 cGISH
      signals in barley. Further advantages of this technique are: (1) the fast and
      straightforward preparation of the probe; (2) the generation of signals with high
      intensity and reproducibility even without signal amplification; and (3) no
      requirement of species-specific sequences suitable for molecular karyotype
      analysis. Hybridization can be performed without competitive DNA. Signal
      detection without significant background is possible under low stringency
      conditions. The universal application of this fast and simple one-step
      fluorescence banding technique for plant cytogenetic and plant genome evolution
      is discussed.

PMID- 11448039
TI  - Characterization of a mitotic mutant of durum wheat.
AB  - An ethyl methanesulfonate-induced mitotic mutant of durum wheat (Triticum
      turgidum L. var. durum; 2n = 4x = 28) was found. We have characterized the mutant
      to determine the mechanism of abnormal cell division and to test for temperature
      effects on abnormal cell division. Stained root-tip meristems and pollen mother
      cells were studied with brightfield, phase contrast, and immunofluorescence
      microscopy. Abnormal cells included metaphase cells with a multiple of the normal
      complement (8x = 56, or 16x = 112), multinucleate cells, 4C, 8C, or 16C
      mononucleate cells, and cells exhibiting incomplete cytokinesis. The mutant had
      three classes of pollen mother cells: euploid with normal bivalent pairing,
      multiploid with bivalent pairing, and multiploid with multivalent pairing.
      Preprophase bands and spindles were normal in mononucleate cells. Some cells had
      asymmetrical phragmoplasts and phragmoplast dismantling that produced incomplete
      cytokinesis. Failure of cytokinesis followed by nuclear fusion were the
      mechanisms of abnormal cell division. To test for temperature sensitivity of the
      mutant, seedlings were germinated under six different temperature regimes. As
      germination temperature increased, the frequency of abnormal cells increased.
      When the mutant was crossed as the female with durum wheat, 3% of hybrids were
      hexaploid, indicating that functional-unreduced gametes had formed in megaspores.

PMID- 11448040
TI  - Heterogeneity of rDNA distribution and genome size in Silene spp.
AB  - Genus Silene L. (Caryophyllaceae) contains about 700 species divided into 44
      sections. According to recent taxonomic classification this genus also includes
      taxa previously classified in genera Lychnis and Melandrium. In this work, four
      Silene species belonging to different sections were studied: S. latifolia (syn.
      Melandrium album, Section Elisanthe), S. vulgaris (Inflatae), S. pendula
      (Erectorefractae), and S. chalcedonica (syn. Lychnis chalcedonica,
      Lychnidiformes). Flow cytometric analysis revealed a genome size of 2.25 and 2.35
      pg/2C for S. vulgaris and S. pendula and of 5.73 and 6.59 pg/2C for S. latifolia
      and S. chalcedonica. All four species have the same chromosome number including
      the pair of sex chromosomes of the dioecious S. latifolia (2n = 2x = 24). Double
      target fluorescence in-situ hybridization revealed the chromosomal locations of
      25S rDNA and 5S rDNA. A marked variation in number and localization of rDNA loci
      but no correlation between the numbers of rDNA clusters and genome size was
      found. FISH and genome size data indicate that nuclear genomes of Silene species
      are highly diversified as a result of numerous DNA amplifications and
      translocations.

PMID- 11448041
TI  - Highly comprehensive karyotype analysis by a combination of spectral karyotyping
      (SKY), microdissection, and reverse painting (SKY-MD).
AB  - A technique disclosing most information about chromosome modifications is the
      technique of choice for the analysis of chromosome alterations. The newly
      developed method for microdissection of fluorescence-labeled chromosomes (FISH
      MD) can improve upon this expectation in combination with 24-color spectral
      karyotyping (SKY). The highly efficient way to detect chromosome modifications by
      SKY and the detailed specification of aberrant chromosomes by FISH-MD prompted us
      to use both techniques in a combined approach called SKY-MD. First, an overview
      of chromosomal aberrations is obtained by spectral karyotyping and subsequently
      the derivative chromosomes recognized are characterized in a highly specific
      manner by microdissection and reverse painting. A small quantity of isolated
      material dissected directly from a 24-color metaphase is sufficient to obtain
      very detailed information about the chromosome regions and the breakpoints
      involved in the derivative chromosomes. Therefore, the combination of spectral
      karyotyping and microdissection in one procedure, and reverse painting can
      characterize chromosomal aberrations with a degree of specificity hitherto
      unknown from individual karyotyping experiments. In this article we compare the
      efficiency of both the SKY technique and that of classical microdissection with
      the efficiency obtained by SKY-MD.

PMID- 11448042
TI  - Evolution of 5S rRNA gene families in Drosophila.
AB  - In Drosophila virilis, the three clusters of 5S rRNA genes on chromosome 5
      comprise two different gene families (B and C), which differ profoundly in the
      organization of their spacer sequences. While C-type genes, which are found in
      two of the clusters, exhibit a true repetitive character, the B-type genes of the
      third cluster are each embedded in completely different genomic environments.
      Southern blots of genomic DNA of different D. virilis subspecies, D. hydei and D.
      melanogaster probed with 5S rRNA gene spacer and coding sequences demonstrate the
      specificity of C-type sequences for the D. virilis species group. The comparative
      analysis of flanking sequences of 5S rRNA genes of D. virilis, members of the D.
      melanogaster species subgroup and of the blowfly Calliphora erythrocephala
      reveals the existence of conserved sequence motifs both in the 5' upstream and 3'
      downstream flanking regions. Their possible roles in the control of expression
      and processing of the 5S rRNA precursor molecule are discussed.

PMID- 11448044
TI  - Effect of the type of base and number of reaction steps on the degree of
      quaternization and molecular weight of N-trimethyl chitosan chloride.
AB  - N-Trimethyl chitosan chloride (TMC), a chemically modified derivative of
      chitosan, is the first chitosan derivative shown to be an effective absorption
      enhancer for peptide and protein drugs across mucosal epithelia. TMC is
      synthesized by reductive methylation with methyl iodide in the presence of a
      strong base such as sodium hydroxide. In this reaction, the primary amino group
      on the C-2 position of chitosan is changed to a quaternary amino group. The
      charge density, as determined by the degree of quaternization, and probably also
      the molecular weight of TMC are important factors that influence the absorption
      enhancement effect and toxicity of this polymer. The molecular weight of the
      starting polymer decreases during the synthesis procedure due to factors such as
      the strong alkaline environment and elevated experimental temperatures. This
      study investigated the effects of two different bases, sodium hydroxide and
      dimethyl amino pyridine, together with a varying number and duration of reaction
      steps, on the degradation and the degree of quaternization of TMC polymers. 1H
      NMR (nuclear magnetic resonance) spectra showed a major increase in the degree of
      quaternization (21%-59%) of TMC with an increase in the number of reaction steps
      when sodium hydroxide was used as the base. Intrinsic viscosity values indicated
      that the use of dimethyl amino pyridine did not cause polymer degradation to the
      same extent as sodium hydroxide, but that the degree of quaternization of TMC
      stayed low (7.3%-9.6%) even when the number of reaction steps was increased. A
      combination of the two bases did not reduce polymer degradation, while the degree
      of quaternization was limited to relatively low values (12.5%-34.4%).

PMID- 11448043
TI  - A tandem repetitive sequence located in the centromeric region of common wheat
      (Triticum aestivum) chromosomes.
AB  - Although Tail-family sequences are present in the subtelomeric region of Leymus
      racemosus, it became apparent in the present study that such sequences are also
      present in the centromeric region of common wheat (Triticum aestivum). These
      sequences hybridized to all chromosomes with various degrees of signal strength.
      FISH using Tail and Ty3/gypsy, a conservative sequence in cereal centromeres,
      revealed a complicated arrangement of both sequences in all wheat chromosomes at
      once. Unlike the Arabidopsis centromeres characterized by massive tandem arrays
      of 180-bp family with flanking paracentromeric retrotransposons in all
      chromosomes, wheat chromosomes showed various arrangement patterns of Tail and
      Ty3/gypsy sequences depending on the chromosome; Tail-family sequences were
      scattered in many wheat centromeres as isolated colonies instead of forming
      uninterrupted solid tandem arrays. This pattern may have resulted from
      retrotransposon insertion within pre-existing Tail-tandem arrays or a two-step
      amplification mechanism of the Tail family where each Tail colony was amplified
      to form arrays independently after the insertion of Tail-family sequences along
      the entire centromere. Although sequence analysis of centromeric Tail repeats in
      wheat and subtelomeric Tail repeats in L. racemosus showed variable and
      conservative regions between the two repeats, they did not show a distinctive
      difference phylogenically. The widespread presence of tandem repetitive sequences
      in the eucaryotic centromere suggests a significant role for them in centromeric
      formation.

PMID- 11448045
TI  - Extrusion-Spheronization of blends of carbopol 934 and microcrystalline
      cellulose.
AB  - We evaluated the effects of several process variables on the pharmaceutical and
      drug release properties of extrusion-spheronization pellets of blends of Carbopol
      934 and microcrystalline cellulose (MCC) containing a high proportion of
      Carbopol. The model drug was theophylline. Rheological monitoring during mixing
      was by mixer torque rheometry. Carbopol:MCC blends wetted with a CaCl2 solution
      showed different rheological behavior compared to blends with a high proportion
      of MCC wetted with water only. In contrast to previous suggestions, the optimal
      wetting point for extrusion did not coincide with the point of peak torque, but
      occurred just beyond this point, at much lower torque. The influence of process
      variables on blend properties was investigated with a three-variable factorial
      design (Carbopol:MCC ratio, wetting liquid proportion, CaCl2:Carbopol ratio), and
      the influence of process variables on pellet properties with a four-variable
      design (the variables listed plus extrusion screen hole diameter). Blend torque
      values were strongly influenced by CaCl2 proportion, while mean pellet diameter
      was influenced by Carbopol:MCC ratio. Mean pellet diameter also differed
      depending on whether the pellets contained theophylline. The observed among
      formulation differences in theophylline release kinetics were largely explained
      by differences in pellet size and theophylline hydration state. Compaction of
      pellets to form tablets markedly modified the drug release profile, making it
      biphasic.

PMID- 11448046
TI  - Chitosan-alginate microparticles as a protein carrier.
AB  - The oral administration of peptidic drugs requires their protection from
      degradation in the gastric environment and the improvement of their absorption in
      the intestinal tract. For these requirements, a microsystem based on cross-linked
      alginate as the carrier of bovine serum albumin (BSA), used as a model protein,
      was proposed. A spray-drying technique was applied to BSA/sodium alginate
      solutions to obtain spherical particles having a mean diameter less than 10
      microm. The microparticles were hardened using first a solution of calcium
      chloride and then a solution of chitosan (CS) to obtain stable microsystems. The
      cross-linking process was carried out at different CS concentrations and pH
      values of the cross-linking medium. The CS concentration affected the BSA loading
      in the microparticles prepared at a pH value less than the protein isoelectric
      point (pI). Moreover, the BSA loading at a pH value less than the pI was higher
      than that at a pH similar to the pI regardless of the CS concentration. This
      finding could be attributable to the formation of a BSA/alginate complex. The
      evaluation of the interaction between BSA and alginate at different pH values by
      means rheological measurements confirmed this hypothesis. This approach may
      represent a promising way to devise a microcarrier system with appropriate size
      for targeting the Peyer's patches, with appropriate immobilization capacity, and
      suitable for the oral administration of peptidic drugs.

PMID- 11448047
TI  - Investigation of some commercially available spacer devices for the delivery of
      glucocorticoid steroids from a pMDI.
AB  - Five commercially available spacers were investigated to determine their
      influence on the percentage of drug retained in the spacer device, percentage
      fine particle fraction (FPF), percentage deposited in the induction port, mass
      median aerodynamic diameter (MMAD), and geometric standard deviation (GSD).
      Betamethasone valerate (BMV) and triamcinolone acetonide (TAA) were used as model
      drugs in the pressurized metered dose inhaler (pMDI) formulations containing the
      propellant HFA 134a. The BMV was dissolved in an ethanol/HFA 134a system, and the
      TAA was suspended in HFA 134a using ethanol as a dispersing agent. The metering
      chamber volume of the valve was either 50 microl or 150 microl. The spacer
      devices investigated included the ACE, Aerochamber, Azmacort, Easivent, and
      Ellipse spacers. Each spacer device was attached to an Andersen Cascade Impactor
      powered by a vacuum pump. Cascade impaction data were used to derive the
      percentage drug deposited in the induction port, MMAD, GSD, and FPF. The BMV
      particles emitted from the spacers were finer than the TAA particles because the
      dissolved drug precipitated as the cosolvent evaporated. The TAA particles had
      significantly larger MMADs because many undissolved drug particles were contained
      within each droplet following actuation. After evaporation of the liquid
      continuous phase, the suspended drug aggregated to form larger agglomerates than
      those particles precipitated from the BMV pMDI solution droplets. The addition of
      a spacer device lowered the MMAD to less than 4.7 microm for particles from both
      the BMV pMDI solution and the TAA pMDI suspension. The addition of a spacer
      device also lowered the percentage drug deposited in the induction port. The FPF
      was significantly increased when a spacer device was used. The MMAD significantly
      decreased when a spacer device was added for the two model drugs when using the
      150-microl metering valves, but the difference was not statistically significant
      when the 50-microl valves were used (P < .05). The GSD was not influenced by the
      use of a spacer device. The use of a spacer device will enhance pMDI therapy by
      reducing the amount of drug deposited in the oropharyngeal region, which will
      lead to fewer instances of local and systemic side effects. In addition, the
      spacer devices investigated will allow a higher dose of drug to reach the deep
      lung, which may permit the use of lower dosage regimens with increased
      therapeutic efficacy.

PMID- 11448048
TI  - Enhancement of dissolution of ethopropazine using solid dispersions prepared with
      phospholipid and/or polyethylene glycol.
AB  - The purpose of this study was to improve the dissolution properties of a poorly
      water soluble and bioavailable drug, ethopropazine HCl (ET), by incorporating the
      drug in three different types of solid dispersion systems. Solid dispersions of
      ET were prepared using 1:1 (w/w) ratios of (1) phospholipid (1,2 dimyristoyl-sn
      glycerophosphocholine) (DMPC), (2) polyethylene glycol 8000 (PEG8000), and (3) a
      novel combination of both DMPC and PEG8000. Using the solvent method of
      preparation, ET and DMPC and/or PEG were dissolved in chloroform, and solvent
      subsequently was evaporated using nitrogen gas. The resulting solid dispersion(s)
      was passed through a 60-mesh sieve. Characterization of ET/DMPC solid dispersion
      was performed by differential scanning calorimetry (DSC) and X-ray diffractometry
      studies. Dissolution studies conducted in phosphate buffered saline (PBS) (pH
      7.4, 37 degrees C +/- 0.5 degrees C) using the USP type II (paddle) dissolution
      apparatus showed significant increases in the dissolution rate of ET with all the
      solid dispersions in this study. Specifically, within the first 5 min (D5), solid
      dispersions containing ET/DMPC (1:1) showed an eightfold increase in dissolution;
      in combination with DMPC and PEG8000 (1:1), there was an approximately sixfold
      increase; and a fourfold increase was observed with PEG8000 (1:1). Complete
      dissolution of all solid dispersions occurred within 60 min (D60) of the run.
      Storage of the ET/DMPC sample for over 4.5 months revealed a decrease in the
      dissolution rate when compared to freshly prepared sample. Overall, it was
      concluded that the dissolution rate of ET significantly improved when dispersed
      in all the selected carrier systems. However, the solid dispersion of ET/DMPC was
      observed to be superior to the other combinations used.

PMID- 11448049
TI  - Study of drug release from pellets coated with Surelease containing
      hydroxypropylmethylcellulose.
AB  - The release of metoclopramide hydrochloride (a very water soluble cationic drug)
      and diclofenac sodium (a sparingly soluble anionic drug) from pellets coated with
      Surelease containing hydroxypropylmethylcellulose (HPMC) at different coating
      loads was investigated. The release rates of either drug at each coating
      composition decreased as the coating load increased. Inclusion of HPMC E15
      increased the release rates of both drugs compared to pellets coated only with
      Surelease. This was thought to be due to the leakage of the soluble part of the
      film (HPMC E15) during dissolution, which left pores for drug release. The
      Surelease:HPMC E15 ratio had a major role in the release rates of drugs. Addition
      of HPMC E15 into Surelease did not change the release mechanism for
      metoclopramide hydrochloride (the mean value of n approximately 0.57) from that
      of Surelease alone, and diffusion remained the main mechanism controlling the
      release. However, the release exponent (approximately 1.28) increased for
      diclofenac sodium on addition of HPMC E15, indicating a dissolution-controlled
      mechanism. Despite its lower water solubility, diclofenac sodium was released
      slightly faster than metoclopramide hydrochloride from pellets coated with
      Surelease containing HPMC E15 at equivalent coating loads.

PMID- 11448050
TI  - Acrylic resins as rate-controlling membranes in novel formulation of a nine-day
      17beta-estradiol transdermal delivery system: in vitro and release modifier
      effect evaluation.
AB  - The feasibility of transdermal controlled delivery system of 17beta-estradiol was
      investigated by conducting in vitro release studies. Several new 17beta-estradiol
      unilaminate adhesive devices capable of releasing 17beta-estradiol in a
      controlled fashion over a 24-h, 36-h, 96-h, 104-h, 168-h, and 216-h period have
      been developed using acrylic resins (Eudragits E100, RSPO, and RLPO) as adhesive
      and rate-controlling polymers. The in vitro release profiles of 17beta-estradiol
      from various TDS unilaminate devices were characterized in a new developed
      dissolution tester vessel (total volume 200 ml), using a new paddle. The release
      of drug from different formulations was measured by a sensitive high-performance
      liquid chromatographic (HPLC) method. The release of drug from all prepared
      adhesive devices seems to obey zero-order kinetics (r > 0.98). The effect of two
      different plasticizers (acetyltriburyl citrate [ATBC] and triethyl citrate [TEC])
      on the release patterns of 17beta-estradiol from TDS formulations was studied,
      and they were almost identical. The effect of two different release modifiers,
      propylene glycol (PG) and myristic acid (MA), on the release pattern of 17beta
      estradiol from prepared unilaminate devices was evaluated. It was shown that the
      use of these release modifiers significantly increased the release of 17beta
      estradiol from a TDS unilaminate patch. Furthermore, these data clearly
      demonstrated that the acrylic resins are suitable polymers for the preparation of
      17beta-estradiol TDS adhesive devices.

PMID- 11448051
TI  - Channeling agent and drug release from a central core matrix tablet.
AB  - A new oral dosage form for controlled and complete release of drug after a
      predetermined lag time is described. The system, designed to exploit the
      relatively constant small intestine transit time, consists of a drug-containing
      core coated with a polymeric matrix formed by a channeling agent (NaCl, mannitol,
      and Emdex) and an inert polymer (Eudragit RS100). The lag time was found to be
      dependent on type and particle size of the channeling substances used. Also,
      rheological properties of the binary mixtures (channeling substance--polymer) can
      affect the lag time periods. On the other hand, the release kinetics were found
      to be influenced significantly by excipient type and particle size. Results
      obtained from in vitro dissolution testing demonstrated that this device
      potentially could be used to deliver drugs orally for up to once-a-day dosing at
      controllable rates.

PMID- 11448052
TI  - Physicochemical characterization and evaluation of buccal adhesive tablets
      containing omeprazole.
AB  - The objective of this study was to develop an effective omeprazole buccal
      adhesive tablet with excellent bioadhesive force and good drug stability in human
      saliva. The omeprazole buccal adhesive tablets were prepared with various
      bioadhesive polymers, alkali materials, and croscarmellose sodium. Their
      physicochemical properties, such as bioadhesive force and drug stability in human
      saliva, were investigated. The release and bioavailability of omeprazole
      delivered by the buccal adhesive tablets were studied. As bioadhesive additives
      for the omeprazole tablet, a mixture of sodium alginate and
      hydroxypropylmethylcellulose (HPMC) was selected. The omeprazole tablets prepared
      with bioadhesive polymers alone had bioadhesive forces suitable for a buccal
      adhesive tablet, but the stability of omeprazole in human saliva was not
      satisfactory. Among alkali materials, only magnesium oxide could be an alkali
      stabilizerfor omeprazole buccal adhesive tablets due to its strong waterproofing
      effect. Croscarmellose sodium enhanced the release of omeprazole from the
      tablets; however, it decreased the bioadhesive forces and stability of omeprazole
      tablets in human saliva. The tablet composed of omeprazole/sodium
      alginate/HPMC/magnesium oxide/croscarmellose sodium (20/24/6/50/10 mg) could be
      attached on the human cheek without disintegration, and it enhanced the stability
      of omeprazole in human saliva for at least 4 h and gave fast release of
      omeprazole. The plasma concentration of omeprazole in hamsters increased to a
      maximum of 370 ng/ml at 45 min after buccal administration and continuously
      maintained a high level of 146-366 ng/ml until 6 h. The buccal bioavailability of
      omeprazole in hamsters was 13.7% +/- 3.2%. These results demonstrate that the
      omeprazole buccal adhesive tablet would be useful for delivery of an omeprazole
      that degrades very rapidly in acidic aqueous medium and undergoes hepatic first
      pass metabolism after oral administration.

PMID- 11448053
TI  - Evaluation of stereoselective dissolution of racemic salbutamol matrices prepared
      with commonly used excipients and 1H-NMR study.
AB  - The purpose of this work was to examine the in vitro enantioselective dissolution
      of salbutamol from matrix tablets containing various chiral excipients, such as
      gamma cyclodextrin (gamma-CD), heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DM
      beta-CD), sulfobutyl-beta-cyclodextrin (SBE-beta-CD),
      hydroxypropylmethylcellulose (HPMC), and egg albumin. In this study, two types of
      tablets were prepared; the coated tablet contained the complex of racemic
      salbutamol and cyclodextrin (gamma-CD, DM-beta-CD, and SBE-beta-CD), and the
      uncoated tablet was composed of the drug with either HPMC or egg albumin.
      Subsequently, these formulations were evaluated for enantioselective release. The
      results revealed that the formulations containing either SBE-beta-CD, HPMC, or
      egg albumin had no enantioselective release, while the formulation with DM-beta
      CD gave slightly different release of the two enantiomers at the end of the
      dissolution profile. The formulation containing gamma-CD provided significant
      stereoselectivity throughout the dissolution profile. The release of the eutomer
      R-salbutamol was higher than that of the distomer S-salbutamol from the gamma-CD
      tablet. In addition, the enantioselective interaction for the gamma-CD inclusion
      complex was investigated by 1H-NMR (nuclear magnetic resonance) spectroscopy and
      gave evidence to support the enantioselectivity obtained on dissolution.

PMID- 11448054
TI  - A brief report on some physiological parameters of streptozocin-diabetic rat.
AB  - Several biological changes occur when streptozocin is given to experimental
      animals. The rat streptozocin (STZ) model is extensively used in diabetic
      experiments. In this brief report, the main physiological characteristics of rats
      injected with streptozocin are presented. These characteristics are manifested by
      weight loss, organ weight reduction, serum glucose elevation, decrease in serum
      insulin level, and other enzyme and hormonal changes. A collection of these
      parameters may be helpful in establishing a database to describe this model.

PMID- 11448055
TI  - Design and evaluation of a two-layer floating tablet for gastric retention using
      cisapride as a model drug.
AB  - A new kind of two-layer floating tablet for gastric retention (TFTGR) with
      cisapride as a model drug was developed. The in vitro drug release was
      determined, and the resultant buoyancy and the time-buoyancy curve were plotted.
      Because of the sodium bicarbonate added to the floating layer, when immersed in
      simulated gastric fluid (SGF) the tablet expands and rises to the surface, where
      the drug is gradually released. The in vitro drug release of this kind of two
      layer dosage was controlled by the amount of hydroxypropylmethylcellulose (HPMC)
      in the drug-loading layer. Generally, the more HPMC, the slower the drug
      releases. Because cisapride has greater solubility in SGF than simulated
      intestinal fluid (SIF), its in vitro drug dissolution in SGF is faster than in
      SIF. One of the distinguishing characteristics of this kind of tablet is the
      separate regulation of buoyancy and drug release. The idea developed in this
      experiment can be used as a general modelfor the design of other tablets for
      gastric retention.

PMID- 11448056
TI  - Drug adjuvant interaction study using DSC supported by isothermal method.
AB  - Extensive work has been done in the field of drug adjuvant interaction studies
      using differential scanning calorimetry (DSC), but conclusive interpretive
      techniques could not be reached since very few workers supplemented their work by
      conventional isothermal stability testing methods. This work compared the drug
      adjuvant thermogram with results obtained from isothermal stability studies and
      used it to reiterate the results of the drug adjuvant thermograms. In the
      formulation of ascorbic acid in a cosmetic preparation, the various adjuvants
      were tested for interactions first by the isothermal stability testing technique,
      which was followed by DSC scanning of the drug adjuvant. The results of the two
      methods were compared and correlated.

PMID- 11448057
TI  - The development of novel mouse monoclonal antibodies against the CC531 rat colon
      adenocarcinoma.
AB  - In this paper we describe 4 new monoclonal antibodies to be applied in rat models
      for cancer. The monoclonal antibodies were obtained by immunizing Balb/c mice
      with CC531 rat colon adenocarcinoma cells. Hybridomas were produced and 4 were
      selected for their reactivity with CC531 in vitro (MG1, 2, 3 and 4). All 4
      antibodies recognized other rat tumour cell lines and showed limited cross
      reactivity with normal rat tissues. Intraperitoneally injected MG1, 2 and 4 homed
      to in vivo growing, artificially induced CC531 liver metastases. In these in vivo
      experiments, limited cross-reactivity with normal rat tissues, predominantly of
      the gastro-intestinal tract, was found. MG4 was found to enhance lysis of CC531
      tumour cells mediated by IL-2 activated, cultured natural killer cells. These
      antibodies are potentially useful for antibody-based laboratory techniques and
      for investigation of antibody-based immunotherapy of cancer in a rat model.

PMID- 11448058
TI  - Venesection needle coring increases positive results with RT-PCR for detection of
      circulating cells expressing CEA mRNA.
AB  - We assessed whether circulating cell positivity using RT-PCR for carcinoembryonic
      antigen (CEA) cDNA was affected by venesection via a needle compared with a pre
      aspirated venous cannula, and by increased PCR cycles. Systemic blood was sampled
      by needle and pre-aspirated cannula in 101 healthy individuals with no cancer
      history. After erythrocyte removal, samples were subjected to RT-PCR using
      specific primers for CEA, with 29 or 35 RT-PCR cycles. There was a significant
      difference between the number of subjects whose samples were negative when
      collected via needle venesection and positive when collected via pre-aspirated
      cannula, compared with positive by needle venesection and negative by pre
      aspirated cannula for both 29 (P = 0.016) and 35 (P = 0.0111) RT-PCR cycles.
      Venesection technique (P = 0.01) and number of cycles (P = 0.003) were
      significant predictors of a positive result. Positive results in healthy subjects
      were reduced to less than 3% when an aspirated cannula was used for venesection
      and >29 PCR cycles were avoided.

PMID- 11448059
TI  - Liver metastatic ability of human melanoma cell line is associated with losses of
      chromosomes 4, 9p21-pter and 10p.
AB  - Genetic changes underlying the aggressive progression of human cutaneous melanoma
      are not completely understood. In order to characterise genetic alterations
      associated with the metastatic behaviour of this neoplasm we used comparative
      genomic hybridisation (CGH) in combination with fluorescence in situ
      hybridisation (FISH) on an experimental metastatic model of three related human
      melanoma cell lines. Tumour lines were selected based on their various metastatic
      capacity to liver in immunosuppressed mice. The parental cell line (A2058) was a
      human amelanotic melanoma cell line, adaptation of this line to in vivo growth as
      xenograft the HT168 tumour and its cell line was established. After intrasplenic
      transplantation of HT168 cells into immunosuppressed mice, a highly metastatic
      variant (HT168-M1) was selected. Several chromosomal aberrations common to all
      three lines indicating common clonal origin, as well as additional non-shared
      chromosomal changes were found. The original cell line (A2058) exhibited the
      highest number of genetic changes. Chromosomal alterations present only in the
      highly metastatic line (HT168-M1) involved losses on chromosome 4, 9p21.3-pter
      and 10p. Chromosome copy number patterns and the nature of chromosome 4 loss were
      further investigated by FISH using different centromeric probes and a chromosome
      4 painting probe. According to our CGH and FISH results we assume that
      alterations present only in the aggressive metastatic subline are associated with
      the increased - metastatic potential. Our observations further support the
      hypothesis, based on some recently published data, that certain (so far
      unidentified) suppressor genes having an important role in tumour progression are
      located on these chromosomes.

PMID- 11448060
TI  - Role of tissue factor pathway inhibitor-2 (TFPI-2) in amelanotic melanoma (C-32)
      invasion.
AB  - Human tissue factor pathway inhibitor-2 (TFPI-2), also known as placental protein
      (PP5) and matrix-associated serine protease inhibitor (MSPI), is a 32-kDa
      extracellular matrix (ECM) protein consisting of three tandomly arranged Kunitz
      type domains that inhibits plasmin, trypsin, chymotrypsin, cathepsin G and plasma
      kallikrein but not urokinase and tissue-type plasminogen activators or thrombin.
      Earlier studies in our laboratory revealed that the production of TFPI-2 is
      reduced or absent during the tumor progression of human gliomas. In the present
      study, we investigated the role of TFPI-2 in the invasiveness of the amelanotic
      melanoma cell line C-32. We stably transfected C-32 cells with a vector capable
      of expressing TFPI-2 in a sense orientation (0.7 kb). TFPI-2 protein production
      was then determined by western blotting and the mRNA level by northern blotting
      in parental and stably transfected (vector and sense) clones. The levels of TFPI
      2 protein and mRNA were significantly higher in the sense clones, but neither was
      detected in parental and vector control clones. In addition, in vitro Matrigel
      invasion/migration assays revealed that the invasive behavior of sense clones was
      inhibited compared with the behavior of parental and vector clones. This is the
      first study to show that the upregulation of TFPI-2 plays a significant role in
      reducing the invasive behavior of human amelanotic melanomas.

PMID- 11448061
TI  - Inhibitory effect of 1-O (2 methoxy) hexadecyl glycerol and phenylbutyrate on the
      malignant properties of human prostate cancer cells.
AB  - The ability of the naturally occurring ether lipid, 1-O (2 methoxy) hexadecyl
      glycerol (MHG), and phenylbutyrate (BP) to inhibit cellular proliferation,
      anchorage-independent growth and cellular invasion in the human prostate cancer
      LnCap and DU145 cells was determined. Both MHG and PB inhibited the malignant
      properties of these prostate cancer cells. The concentrations required to achieve
      similar inhibitory effect, however, were significantly different for these two
      agents. MHG inhibited cell growth with equal potency in these cell lines with an
      IC-50 value of 93 microM for LnCap, and 97 microM for DU145. The IC-50 values for
      PB were 1.3 mM and 7.3 mM, respectively, for LnCap and DU145 cells. Both MHG and
      PB (IC-50 concentrations) inhibited the anchorage-independent growth and cellular
      invasion in these cells. Over 50% inhibition of anchorage-independent growth was
      achieved for both LnCap and DU145 cells by PB, while a lesser degree of
      inhibition was achieved with MHG. Both MHG- and PB-treated cells showed a reduced
      propensity to invade matrigels. Invasion of PB-treated LnCap and DU145 cells was
      reduced, respectively, by approximate 41 and 30% when compared to untreated
      control cells, while invasion of MHG-treated LnCap and DU145 cells was reduced to
      a lesser extent. Because differentiation-inducing agents may possess
      chemopreventive properties, the use of naturally occurring MHG and nontoxic PB in
      the chemoprevention of malignant diseases warrants further investigation.

PMID- 11448062
TI  - Tumor specific activation of the VEGF/KDR angiogenic pathway in a subset of
      locally advanced squamous cell head and neck carcinomas.
AB  - Vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and flk
      1(KDR), constitute an important angiogenic pathway which, under hypoxic
      conditions, is up-regulated in many solid tumours. We used the monoclonal
      antibody 11B5, specific for recognizing VEGF expression and the 'VEGF/flk-1(KDR)
      complex' on tumour endothelium, to assess free VEGF protein expression and
      VEGF/receptor activated microvessel density (aMVD) in a series of 104 inoperable
      locally advanced squamous cell carcinomas of the head and neck, treated with
      chemo-radiotherapy. High VEGF expression in cancer cells was strongly associated
      with high VEGF/receptor expression in the vasculature. The high VEGF expression
      and the aMVD were not associated with the standard microvessel density (sMVD), as
      assessed with the monoclonal antibody anti-CD31 and, were not detected in normal
      tissue. An increased sMVD, however, was significantly related with the expression
      thymidine phosphorylase (TP), and also with the nuclear accumulation of the
      oncoprotein p53, but neither p53 nor TP was associated with VEGF expression by
      cancer cells or VEGF/receptor complex aMVD. In 35% of cancer cases examined, more
      than 20% of the microvessels assessed with anti-CD31 also expressed the VEGF/KDR
      complex. The vasculature of the normal head and neck mucosa did not express the
      VEGF/KDR complex. There was no association between VEGF expression or
      VEGF/receptor complex aMVD and response to chemo-radiotherapy or patient's
      survival. It is concluded that activation of the angiogenic pathway VEGF/flk
      1(KDR) is tumor specific in a subgroup of locally advanced squamous cell
      carcinomas of the head and neck. Selective destruction of this type of
      vasculature, using immunoconjugates directed against the VEGF/receptor complex,
      may prove therapeutically useful for patients with a high tumoral VEGF/flk-1(KDR)
      activated microvessel fraction.

PMID- 11448063
TI  - Membrane-type 1 matrix metalloproteinase enhances lymph node metastasis of
      gastric cancer.
AB  - The mechanisms of the lymph node metastasis remain unclear. We demonstrate the
      role of MT1-MMP on the lymph node metastasis using in vivo experimental model of
      lymph node metastasis by orthotopic implantation of MT1-MMP transfected gastric
      cancer cell line in the stomach of nude rats. TMK-1 cell line without expression
      of MT1-MMP was transfected with the pcDNA3 plasmid containing a 3.4-kb MT1-MMP
      cDNA fragment by calcium phosphate method, and the transfected cell line was
      designated as TMK-MT. Western blot and RT-PCR analyses showed the specific bands
      corresponding to MT1-MMP in the TMK-MT cells. By gelatin zymography, the
      activated form (62-kDa) of MMP-2 was identified in the medium of TMK-MT cell
      line, but was not detected in TMK-1 cells. Six weeks after orthotopic
      implantation of TMK-1 and TMK-MT xenografts of nude mouse-subcutaneus tumor into
      the stomach of nude rats, gastric tumors were found in all the animals.
      Histologically, the lymphatic invasion was found in the submucosa of the TMK-MT
      gastric tumors. Lymph node metastasis was not detected in nude rats bearing TMK-1
      gastric tumor (0/8). In contrast, lymph node metastasis was detected in five out
      of 8 rats, bearing TMK-MT gastric tumor. MT1-MMP immunoreactivity was found on
      the cell membrane and cytoplasm of TMK-MT cells not only in the lymph node
      metastasis but also in the stomach tumor. These results suggest that MT1-MMP
      overexpression induced by transfection of its gene may promote lymph node
      metastasis of transformed cells.

PMID- 11448064
TI  - Nitric oxide (NO), methylation and TIMP-1 expression in BL6 melanoma cells
      transfected with MHC class I genes.
AB  - We have previously found that transfection of BL6-8 melanoma cells with the H-2K,
      but not H-2D/L genes resulted in loss of their metastatic ability that was
      associated with decrease in their invasiveness and up-regulation of TIMP-1
      expression. In the present study using the methylation-specific PCR (MSP) we
      found that lack of TIMP-1 expression in BL6-8 is associated with methylation in
      the TIMP-1 5' regulatory area. In the H-2Kb transfected CL8-1 melanoma cells up
      regulation of TIMP-1 was in parallel with loss of TIMP-1 gene methylation.
      Treatment of BL6-8 with 5-azacytidine or with an inhibitor of histone deacetylase
      trichostatin A resulted in up-regulation of TIMP-1 expression. These results
      indicate that methylation and histone deacetylation play an important role in
      transcription repression of TIMP-1 in BL6 melanoma cells. Some data showed that
      nitric oxide (NO) could affect methylation and expression of various gene.
      Therefore we analyzed NO production in B16 melanoma cell lines with different
      expression of TIMP-1. We have found that B16F10 and BL6-8 melanoma cells do not
      express TIMP-1 and do not produce nitric oxide (NO) even after stimulation with
      IFN-gamma and LPS. However, BL6-8 cells transfected with H-2Kb or H-2Kd, but not
      H-2Dd or H-2Ld gene expressed TIMP-1 and produced NO constitutevely. NO
      production in these cells was further stimulated by IFN-gamma and LPS. Northern
      blot analysis showed that expression of iNOS was paralleled with TIMP-1
      expression in the tested melanoma cells. However, NO produced by SNAP or
      inhibition of NO production by NMA did not affect TIMP-1 expression in the tested
      melanoma cells. Thus, TIMP-1 expression and NO production in BL6 melanoma cells
      transfected with MHC class I gene coincides but it remains unclear whether NO is
      responsible for the change in TIMP-1 methylation and expression.

PMID- 11448065
TI  - Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial
      endothelial cell interactions.
AB  - The purpose of this study was to investigate the roles of matrix
      metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      in the formation of capillary structures by human brain microvascular endothelial
      cells cocultured with SNB19 glioblastoma cells. Unstimulated cocultures did not
      form capillaries and produce MMP-9 but stimulation with the protein kinase C
      (PKC) activator 4-phorbol-12-myristate 13-acetate (PMA) produced MMP-9 and
      capillary networks. Addition of recombinant MMP-9 increased capillary formation.
      Anti-MMP-9 antibodies, TIMP-1, the synthetic MMPs inhibitor Batimastat (BB-94),
      and the PKC inhibitor calphostin-C all reduced MMP-9 activity and capillary
      network formation in these cocultures. Cytochalasin-D in the presence of PMA
      suppressed MMP-9 expression and capillary formation, but colchicine-B had no such
      effect. Finally, PMA-induced MMP-9 expression and capillary formation were
      inhibited by the MEKK-specific inhibitor PD98059. These results suggest that MMP
      9 is important in endothelial cell morphogenesis and the formation of capillaries
      in glial/endothelial cocultures in vitro.

PMID- 11448066
TI  - Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation
      of TGF-beta1 and MMPs.
AB  - Transforming growth factor beta1 (TGF-beta1) and matrix metalloproteinases (MMPs)
      produced by tumor cells play important roles in tumor invasion. PSK, a protein
      bound polysaccharide, is widely used in Japan as an immunopotentiating biological
      response modifier for cancer patients. In this study, we focused on the effects
      of PSK on invasiveness, TGF-beta1 production, and MMPs expression in two human
      tumor cell lines, pancreatic cancer cell line (NOR-P1) and gastric cancer cell
      line (MK-1P3). PSK significantly decreased the invasiveness of both cell lines
      through Matrigel-coated filters but did not affect cell viability, proliferation,
      or adhesion. Decreased invasion was associated with the inhibition of TGF-beta1,
      MMP-2, and MMP-9 at both mRNA and protein levels as assessed by reverse
      transcriptase-polymerase chain reaction, gelatin zymography, and enzyme-linked
      immunosorbent assay. Antibody against TGF-beta1 neutralized the MMP activities of
      both cell lines. PSK also suppressed the expression of urokinase plasminogen
      activator (uPA) and uPA receptor but did not change plasminogen activator
      inhibitor-1 (PAI-1) expression. Western blot analysis showed that PSK reduced uPA
      protein expression but not PAI-1 expression in the both cell lines. These results
      indicate that PSK suppresses tumor cell invasiveness through down-regulation of
      several invasion-related factors including TGF-beta1, uPA, MMP-2, and MMP-9.

PMID- 11448067
TI  - Acute effects of stereotactic radiosurgery on the kinetics of glucose metabolism
      in metastatic brain tumors: FDG PET study.
AB  - Hyperacute changes in the expression of glycolysis-associate gene products as
      well as FDG uptake in tumor cells after high-dose irradiation reflect response of
      the cells to noxious intervention and may be a potential indicator of the outcome
      of treatment. To understand acute effects on the kinetics of glucose metabolism
      of tumors in vivo after high-dose irradiation, we analyzed dynamic FDG PET data
      in patients with metastatic brain tumors receiving stereotactic radiosurgery.
      MATERIALS AND METHODS: We studied 5 patients with metastatic brain tumors by
      means of dynamic FDG PET before and 4 hours after stereotactic radiosurgery. Rate
      constants of glucose metabolism (K1*- k3*) were determined in a total of 13
      tumors by a non-linear least squares fitting method for dynamic PET and arterial
      blood sampling data. Rate constants after radiosurgery were compared with those
      before radiosurgery. Changes in the rate constants induced by the therapy were
      also correlated with changes in tumor size evaluated by CT and/or MRI 6 months
      later. RESULTS: Four hours after radiosurgery, the phosphorylation rate indicated
      by k3* was significantly higher (0.080 +/- 0.058) than that before radiosurgery
      (0.049 +/- 0.023) (p < 0.05, paired t test), but there was no significant change
      in the membrane transport rates indicated by K1* and k2*. Although increases in
      the net influx rate constant K* (= K1*k3*/(k2* + k3*)) were correlated with
      increases in k3*, K* after radiosurgery (0.027 +/- 0.011) was not significantly
      different from that before the therapy (0.024 +/- 0.012). The reduction in the
      tumor size was correlated with k3* after radiosurgery. CONCLUSION: Acceleration
      of the phosphorylation process was demonstrated in vivo in metastatic brain
      tumors as early as 4 hours after stereotactic radiosurgery, as shown
      experimentally in vitro in a previous report. The phenomenon may be a sensitive
      indicator of cell damage.

PMID- 11448068
TI  - Arterial fraction of cerebral blood volume in humans measured by positron
      emission tomography.
AB  - In quantitative functional neuroimaging with positron emission tomography (PET)
      and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three
      components, arterial, capillary, and venous blood volumes are important factors.
      The arterial fraction for systemic circulation of the whole body has been
      reported to be 20-30%, but there is no report of this fraction in the brain. In
      the present study, we estimated the arterial fraction of CBV with PET in the
      living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each
      of seven healthy subjects to determine the CBV and arterial blood volume (Va),
      respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into
      account was applied to describe the regional time-activity curve of dynamic
      H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting
      procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003
      ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction
      of CBV was 37%. Considering the limited first-pass extraction fraction of
      H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The
      estimated arterial fraction of CBV was quite similar to that of the systemic
      circulation, whereas it was greater than that (16%) widely used for the
      measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous
      plus capillary fraction of CBV was 63-70% which is a important factor for the
      measurement of CMRO2 with MRI.

PMID- 11448069
TI  - Combined use of bone and bone marrow scintigraphies for the diagnosis of active
      sacroiliitis: a new approach.
AB  - Diagnosis of sacroiliitis (SI) with bone scintigraphy may involve difficulties
      even with a quantitative approach. The aim of this study was to evaluate the
      combined use of bone and bone marrow scintigraphies for the diagnosis of active
      sacroiliitis. Thirty-one patients who were clinically suspected to have SI were
      included in the study. Bone and bone marrow scintigraphies were done after
      injections of 740 MBq of 99mTc-MDP (MDP) and 370 MBq of 99mTc-sulfur colloid (SC)
      respectively with a 2-day interval. Both visual and quantitative assessment of
      MDP uptake and visual assessment of SC uptake in sacroiliac joints were
      performed. Also sacroiliac joint radiographic findings for each patient were
      evaluated and graded from 0 to 4 according to the New York grading system.
      Patients were divided into 2 groups according to their x-ray findings (Group A:
      grade 0-2, Group B: grade 3-4). A total of 14 patients (10 bilateral, 4
      unilateral) had increased MDP uptake with decreased/normal SC uptake. Twelve of
      14 patients had grade 0-2 radiographic changes while only 2 patients had grade 3
      4 radiographic changes. Increased MDP uptake with decreased/normal SC uptake is
      the most common scintigraphic pattern seen in acute phase SI in which
      radiographic findings are generally found to be normal or slightly changed. In at
      least in 8 patients the decreased bone marrow uptake of SC was demonstrated,
      supporting the diagnosis. Although our results did not reveal any significant
      superiority of bone marrow scintigraphy to bone scan for the detection of active
      sacroiliitis, combined use of bone and bone marrow scintigraphies was presented
      as an alternative method to characterize patients with active sacroiliitis.

PMID- 11448070
TI  - Brain perfusion SPECT study with 99mTc-bicisate: clinical pitfalls and improved
      diagnostic accuracy with a combination of linearization and scatter-attenuation
      correction.
AB  - To evaluate the usefulness of a combination of linearization and scatter
      attenuation correction on 99mTc-bicisate (ECD)-single photon emission tomographic
      (SPECT) images, both cerebral blood flow (CBF)-positron emission tomographic
      (PET) images and ECD-SPECT images from fifteen patients with chronic cerebral
      infarction were acquired. We measured radioactivity counts in regions of interest
      (ROIs) on all sets of both images and obtained a 2D scattered graph between ECD
      SPECT and CBF-PET data. To evaluate diagnostic accuracy, the sensitivity,
      specificity and accuracy of ECD-SPECT images were calculated by means of
      discriminant analysis. The same analysis was also performed on the ECD-SPECT
      images corrected by a combination of linearization and scatter-attenuation
      correction. An overall nonlinear relationship was observed between ECD-SPECT and
      CBF-PET. The sensitivity, specificity, and accuracy of ECD-SPECT images were
      69.6%, 91.4% and 73.0%, and those of ECD images corrected by the combination of
      linearization and scatter-attenuation correction were 79.5%, 95.7% and 82.0%
      respectively. The clinically diagnostic accuracy of ECD-SPECT images corrected by
      the combined method apparently increased. So that the linearization with the
      scatter-attenuation method is useful for improving the diagnostic accuracy of ECD
      SPECT images.

PMID- 11448071
TI  - Quantitative analysis of infantile ureteropelvic junction obstruction by diuretic
      renography.
AB  - Infantile hydronephrosis detected by ultrasonography poses a clinical dilemma on
      how to treat the condition. This article reports a retrospective study to
      evaluate infantile hydronephrosis due to suspected ureteropelvic junction (UPJ)
      obstruction by means of standardized diuretic renography and to speculate its
      usefulness for quantitative assessment and management of this condition. Between
      November 1992 and July 1999, 43 patients who had the disease detected in their
      fetal or infantile period were submitted to this study. Standardized diuretic
      renograms were obtained with 99mTc-labeled diethylene-triaminepenta-acetate (Tc
      99m-DTPA) or 99mTc-labeled mercaptoacetyl triglycine (Tc-99m-MAG3) as
      radiopharmaceuticals. Drainage half-time clearance (T 1/2) of the activity at
      each region of interest set to encompass the entire kidney and the dilated pelvis
      was used as an index of quantitative analysis of UPJ obstruction. Initial T 1/2s
      of 32 kidneys with suspected UPJ obstruction were significantly longer than those
      of 37 without obstruction. T 1/2s of kidneys which had undergone pyeloplasty
      decreased promptly after surgery whereas those of units followed up without
      surgery decreased more sluggishly. These findings demonstrate that a standardized
      diuretic renographic analysis with T 1/2 can reliably assess infantile
      hydronephrosis with UPJ obstruction and be helpful in making a decision on
      surgical intervention.

PMID- 11448072
TI  - Different sensitivities to competitive inhibition of benzodiazepine receptor
      binding of 11C-iomazenil and 11C-flumazenil in rhesus monkey brain.
AB  - The in vivo binding kinetics of 11C-iomazenil were compared with those of 11C
      flumazenil binding in rhesus monkey brain. The monkey was anesthetized with
      ketamine and intravenously injected with either 11C-iomazenil or 11C-flumazenil
      in combination with the coadministration of different doses of non-radioactive
      flumazenil (0, 5 and 20 microg/kg). The regional distribution of 11C-iomazenil in
      the brain was similar to that of 11C-flumazenil, but the sensitivity of 11C
      iomazenil binding to competitive inhibition by non-radioactive flumazenil was
      much less than that of 11C-flumazenil binding. A significant reduction in 11C
      flumazenil binding in the cerebral cortex was observed with 20 microg/kg of
      flumazenil, whereas a relatively smaller inhibition of 11C-iomazenil binding in
      the same region was observed with the same dose of flumazenil. These results
      suggest that 11C-flumazenil may be a superior radiotracer for estimating
      benzodiazepine receptor occupancy in the intact brain.

PMID- 11448073
TI  - Usefulness of dual-head coincidence gamma camera with thick NaI crystals for
      nuclear oncology: comparison with dedicated PET camera and conventional gamma
      camera with thin NaI crystals.
AB  - AIM: A comparative study of the images obtained with a dual-head coincidence
      gamma camera with thick NaI crystals (19 mm), a dedicated PET camera with BGO
      crystals and a conventional gamma camera with thin NaI crystals (9.5 mm) was
      conducted to clarify the clinical feasibility of a dual-head coincidence gamma
      camera with thick NaI crystals. METHODS: FDG images of 27 patients with malignant
      tumors were obtained by means of a dual-head coincidence gamma camera with thick
      NaI crystal and a dedicated PET camera with BGO crystals. The images of bone
      scintigraphy in 10 cancer patients obtained with the dual-head coincidence gamma
      camera were compared with those taken by a conventional dual-head gamma camera
      with thin NaI crystals. RESULTS: Patient-basis sensitivity in 27 patients with
      neoplasms and lesion-basis sensitivity of the dual-head coincidence gamma camera
      and the dedicated PET camera were 74.1% and 85.2% (n.s.), 66.7% and 72.2% (n.s.),
      respectively. The tumor to background FDG uptake ratio derived from the
      coincidence gamma camera was significantly lower than that derived from the
      dedicated PET camera (mean +/- s.d.; 3.48 +/- 3.77 vs. 8.12 +/- 8.92, p <
      0.0001), but the tumor to background FDG uptake ratio obtained with both methods
      correlated well (r = 0.84, p < 0.001). Similar whole body bone scans were
      obtained with the dual-head coincidence gamma camera and the conventional dual
      head gamma camera in all 10 patients. CONCLUSION: These results suggest that the
      dual-head coincidence gamma camera with thick NaI crystals has potentially high
      clinical applicability for community hospitals.

PMID- 11448074
TI  - The role of Tc-99m RBC scintigraphy in the differential diagnosis of orbital
      cavernous hemangioma.
AB  - The cavernous hemangioma is the most common benign orbital tumor in adults. Its
      presentation is during the forth to fifth decades with a slowly progressive
      unilateral proptosis. Intraconal cavernous hemangiomas may be difficult to
      differentiate from other intraconal lesions such as schwannomas, meningiomas and
      hemangiopericytomas. We report a case of orbital cavernous hemangioma diagnosed
      by Tc-99m RBC scintigraphy. Tc-99m RBC scintigraphy revealed a typical
      scintigraphic pattern in which there is intense focally increased uptake on the
      delayed image. We conclude that Tc-99m RBC scintigraphy can be a useful method in
      the differential diagnosis of orbital cavernous hemangioma as in hepatic
      hemangioma.

PMID- 11448075
TI  - Tc-99m dextran scintigraphy in the diagnosis of protein losing enteropathy.
AB  - Tc-99m dextran scintigraphy was performed on a 16-year-old male patient with
      protein losing enteropathy. Abnormal leakage of the radiotracer was observed in
      the right upper lumbar area that moved over time and excreted in the stool which
      was suggestive of protein loss. It is concluded that Tc-99m dextran is useful in
      the detection of protein losing enteropathy which is not detected by extensive
      radiological and endoscopic examination.

PMID- 11448076
TI  - Bilateral crossed cerebello-cerebral diaschisis and mutism after surgery for
      cerebellar medulloblastoma.
AB  - A 7-year-old boy developed mutism after surgery for cerebellar medulloblastoma.
      Postoperative magnetic resonance imaging (MRI) showed atrophy of the cerebellar
      vermis and both cerebellar hemispheres, predominantly on the right side. Single
      photon emission computed tomography (SPECT) with technetium-99m-ethyl cysteinate
      dimer (Tc-99m ECD) revealed decreased cerebral blood flow (CBF) in the bilateral
      thalami, bilateral medial frontal lobes, and left temporal lobe in addition to
      the cerebellar vermis and both cerebellar hemispheres when mutism was manifest,
      indicating the existence of bilateral crossed cerebello-cerebral diaschisis
      (BCCCD). Circulatory disturbance in both cerebellar hemispheres secondary to
      tumor resection probably caused BCCCD in both cerebral hemispheres, predominantly
      in the left, via the dentatothalamocortical pathway (DTCP). With recovery of his
      mutism, CBF increased in the right thalamus, bilateral medial frontal lobes and
      left temporal lobe. Thus BCCCD was improved, with only a slight decrease in CBF
      still persisting in the left thalamus. The mechanism of mutism may have involved
      damage to the cerebellar vermis (the site of incision at operation), the left
      dentate nucleus (heavily infiltrated by the tumor) and the right dentate nucleus
      of the cerebellum (affected by circulatory disturbance secondary to acute
      postoperative edema). The SPECT findings suggested that mutism was associated
      with BCCCD-induced cerebral circulatory and metabolic hypofunction in the
      supplementary motor area mediated via the DTCP.

PMID- 11448077
TI  - Central neurocytoma with unusually intense FDG uptake: case report.
AB  - Central neurocytoma is a benign neuronal tumor with a favorable prognosis. This
      tumor is typically characterized by decreased uptake of 18F-fluorodeoxy glucose
      (FDG) and any increased uptake of FDG in patients suffering from this tumor would
      be highly unusual. A case of central neurocytoma with an intense FDG uptake,
      combined with atypical histopathological features and a high proliferation index
      is reported in this paper. A 45-year-old male had a two months' history of right
      hemiweakness. Magnetic resonance (MR) imaging showed a large tumor in the right
      lateral ventricle. Positron emission tomography (PET) with FDG revealed high
      glucose metabolism in the tumor. The histological diagnosis was central
      neurocytoma with atypical features characterized by microvascular proliferation.
      The MIB-1 labeling index, ordinarily smaller than 2.0%, was 7.0%. Conventional
      radiotherapy, with a total dose of 50 Gy, was administered after the surgical
      treatment. The patient returned to his normal daily activities after the
      cessation of radiation therapy.

PMID- 11448078
TI  - Tc-99m-DTPA captopril renography in the detection of renovascular hypertension
      due to renal polar artery stenosis.
AB  - A 24-year-old man whose clinical features were suggestive of renovascular
      hypertension was referred for captopril renal scintigraphy. Captopril renal
      scintigraphy was positive for renovascular hypertension only when the left kidney
      was analyzed in 2 separate regions. Angiography confirmed severe stenosis (90%)
      in the upper branch of the left renal artery.

PMID- 11448079
TI  - Thallium-201 scintigraphy of neuroblastoma: different results for primary tumors
      and skeletal lesions.
AB  - Thallium-201 scintigraphy was performed in 8 children with neuroblastoma, and
      uptake by the tumors was evaluated in comparison with the results of 123I-MIBG
      scintigraphy. No primary tumors or metastatic lymph nodes showed 201Tl
      accumulation, but in 4 cases of bone marrow metastases accompanied by focal
      cortical invasion, the metastatic lesion was demonstrated more clearly on the
      early image than on the delayed image. In another case of bone metastases
      infiltrating cortical bone revealed by 123I-MIBG scintigraphy and biopsy before
      treatment, 201Tl scintigraphy performed after chemotherapy showed abnormal
      accumulation in the tibia, but the second 123I-MIBG scintigraphy performed 1 week
      after the 201Tl scintigraphy showed no abnormal uptake. 201Tl does not appear to
      have good affinity for neuroblastoma, but it accumulates in metastatic skeletal
      lesions. A reactive hypermetabolic bone marrow, and/or inflammatory process and
      periosteal reaction due to the presence of metastatic foci may have induced the
      201Tl accumulation. It seems that 201Tl is not useful for the diagnosis.
      Nevertheless, the discordance between 201Tl uptake in primary tumors and skeletal
      lesions allows speculation on the mechanism of 201Tl accumulation in skeletons.

PMID- 11448080
TI  - Cerebral blood flow and metabolic abnormalities in Alzheimer's disease.
AB  - In this review I summarize observations of PET and SPECT studies about cerebral
      blood flow and metabolic abnormalities in Alzheimer's disease. In very early AD
      flow or metabolism reduces first in the posterior cingulate gyrus and precuneus.
      This reduction may arise from functional deafferentation caused by primary neural
      degeneration in the remote area of the entorhinal cortex that is the first to be
      pathologically affected in AD. Then medial temporal structures and
      parietotemporal association cortex show flow or metabolic reduction as disease
      processes. The reason why flow or metabolism in medial temporal structures shows
      delay in starting to reduce in spite of the earliest pathological affection
      remains to be elucidated. It is likely that anterior cingulate gyrus is
      functionally involved, since attention is the first non-memory domain to be
      affected, before deficits in language and visuospatial functions. However few
      reports have described involvement in the anterior cingulate gyrus. Relationship
      between cerebral blood flow or metabolism and apolipoprotein E genotype has been
      investigated. Especially, the APOE epsilon4 allele has been reported to increase
      risk and to lower onset age as a function of the inherited dose of the epsilon4
      allele. Reduction of flow or metabolism in the posterior cingulate gyrus and
      precuneus has been reported even in presymptomatic nondemented subjects who were
      cognitively normal and had at least a single epsilon4 allele. On the contrary the
      relation of epsilon4 allele to the progression rate of AD has been controversial
      from neuroimaging approaches. PET and SPECT imaging has become to be quite useful
      for assessing therapeutical effects of newly introduced treatment for AD. Recent
      investigations observed significant regional flow increase after donepezil
      hydrochloride treatment. Most of these observations have been made by applying
      computer assisted analysis of three-dimensional stereotactic surface projection
      or statistical parametric mapping instead of a conventional regions of interest
      technique.

PMID- 11448081
TI  - Twenty-four-hour Tl-201 delayed scan underestimates myocardial viability in
      patients with acute myocardial infarction after percutaneous transluminal
      coronary angioplasty.
AB  - BACKGROUND: Myocardial viability in area at risk of acute myocardial infarction
      (AMI) after reperfusion therapy may be underestimated by the 24-hour images due
      to reverse redistribution (r-RD). METHODS: Subjects were 37 AMI patients in whom
      Tc-99m pyrophosphate (PYP)/Tl-201 dual-isotope SPECT was positive. The 24-hour
      delayed scan was performed with only a Tl window. One month later, follow up rest
      Tl SPECT was performed to evaluate myocardial viability. In early (at PYP/Tl-201
      dual-isotope SPECT), 24-hour, and one month follow up Tl studies, Tl uptake in
      the area of AMI was scored into four grades: 3 as normal to 0 as severely
      reduced. The scores were evaluated. RESULTS: Among the 37 AMI lesions, there were
      16 r-RD, 3 RD, 16 fixed defect (FD) and 2 normal (positive PYP and normal Tl).
      Mean Tl scores were early; 1.4 +/- 1.1, 24-hr; 0.9 +/- 0.9 and one month; 1.3 +/-
      1.1. The 24-hour Tl score was lower than the early and one month Tl scores (p <
      0.01). CONCLUSION: Reverse redistribution is frequently observed in an area at
      risk where PYP SPECT was positive. Nuclear medicine physicians should be aware of
      the existence of frequent r-RD in Tl scan to avoid the underestimation of
      myocardial viability in the acute phase after PTCA.

PMID- 11448082
TI  - Esophageal hypomotility in systemic sclerosis: close relationship with pulmonary
      involvement.
AB  - PURPOSE: Esophageal motility was assessed in patients with systemic sclerosis
      (SSc) by scintigraphy and compared with (i) extent of scleroderma, (ii) duration
      of disease, (iii) index of anti-topoisomerase I antibody (topo I), and (iv)
      pulmonary involvement. METHODS: A multiple-swallow test was performed in 47
      patients with SSc in the supine position with 99mTc-DTPA. A region of interest on
      the entire esophagus was defined and the retention ratio (RR) was calculated from
      a time-activity curve. RESULTS: Patients with diffuse scleroderma had higher RRs
      than those with limited scleroderma (48.8% vs. 30.0%; p < 0.05). There was no
      correlation between the RRs and the duration of disease. Patients with positive
      topo I had higher RRs than those who were negative (53.8% vs. 29.7%; p < 0.05).
      Patients with reduced % diffusion capacity for carbon monoxide (%DLCO) had higher
      RRs than those with normal %DLCO (40.5% vs. 19.6%; p = 0.03). Patients with
      reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6%
      vs. 25.0%; p < 0.005). Patients with pulmonary fibrosis had higher RRs than those
      who were negative (58.5% vs. 20.3%; p < 0.00005). CONCLUSION: Esophageal
      dysfunction in patients with SSc showed a correlation with the extent of
      scleroderma, positive topo I, and pulmonary involvement. The RR can be an
      objective clinical marker for the severity of organ fibrosis.

PMID- 11448083
TI  - Validity and sensitivity of a pen computer battery of performance tests.
AB  - This study compared administration of performance tests and visual analogue
      scales (VAS) using a newly developed pen computer (PenC) battery with established
      tests using either pencil-and-paper (PP) or conventional computer. The
      performance of 47 subjects (23 male, age 18-45 years, weight 51-112 kg) was
      compared on the two systems after a dose of ethanol (0.8 g/kg up to a maximum of
      60 g for males, 50 g for females) or placebo in a double-blind two-period
      randomized crossover study. Mean (SD) blood ethanol concentrations (breathalyser)
      were 94.5 mg/100 ml (21.9) at the start of the test battery (30 min post-drink)
      and 80.2 (13.0) at the end of the battery (75 min post-drink). Ethanol effects
      were found in all tests, with most outcome measures showing significant slowing
      or loss of accuracy. Results from the Rapid Visual Information Processing,
      Sentence Verification and Continuous Attention tasks show that the ethanol
      placebo difference and the statistical significance of this difference are in
      close correspondence for the two modes of administration. The pen computer
      versions of these tasks may therefore be used as direct replacements for the
      previous versions. Digit-Symbol and maze tasks did not correspond so closely both
      showing differences in the speed-accuracy trade-off between the two modes. These
      tests, however, are sensitive to the effects of ethanol, and may be useful in
      their own right. Principal component analysis suggested that VAS may be grouped
      into two factors: (1) 'functional integrity', including measures of alertness and
      perceived proficiency, and (2) 'mood', including happiness and sociability.
      Factor 1 showed substantial effects of ethanol, while factor 2 was unchanged.
      There was close agreement between the results from PP and PenC for both factors
      as well as for the Sober-Drunk scale, which showed the expected effects of
      ethanol. Thus pen computer VAS perform in a similar way to the PP versions.

PMID- 11448084
TI  - Psychopathology and personality characteristics in relation to blood serotonin in
      Tourette's syndrome and obsessive-compulsive disorder.
AB  - Family studies suggest an interrelationship between Gilles de la Tourette
      Syndrome (GTS) and some forms of obsessive-compulsive disorder (OCD). Some
      authors consider GTS to be part of a serotonergically mediated cluster of OCD
      spectrum disorders. The present study was undertaken to compare measures of
      psychopathology, personality and blood serotonin between GTS and OCD (without
      tics), and to investigate whether an OCD spectrum hypothesis is supported for
      GTS. Fifteen GTS without OCD subjects, 21 tic with (+) OCD subjects, 15 OCD
      without tic subjects and 26 controls (all without serotonergic medication) were
      evaluated with self-rated and clinician-rated measures of psychopathology and
      personality. Whole blood serotonin (5-HT) and platelet monoamine oxidase activity
      (MAO) was measured, and Spearman's correlations were calculated between whole
      blood 5-HT, MAO and rating scale scores within the entire sample and within
      subgroups. There were main effects of OCD on anxiety, obsessive-compulsive,
      neuroticism and extraversion scores. There were main effects of tics on
      depression, obsessive-compulsive, trait anxiety and neuroticism scores, and on
      platelet MAO. There were interaction effects on platelet MAO, 5-HT, Yale-Brown
      Obsessive-Compulsive Rating Scale severity, trait anxiety and Eysenck Personality
      Questionnaire neuroticism scores. Platelet MAO activity was elevated in tic-free
      OCD subjects when compared to tic + OCD, GTS without OCD and controls. Whole
      blood 5-HT was lowered in tic + OCD patients in comparison to GTS without OCD and
      tic-free OCD subjects. Whole blood 5-HT and obsessive-compulsive severity were
      negatively correlated within OCD without tic patients and MAO and Leyton
      Obsessive Inventory scores were negatively related within GTS without OCD
      patients. The biochemical data of this study suggest that in tic + OCD and in tic
      free OCD patients, 5-HT dysregulations play a role, but not necessarily in pure
      GTS. Serotonergic dysregulations within tic + OCD and tic-free OCD patients are
      distinct, suggesting differences in underlying pathophysiology. The finding that
      obsessions and compulsions can be associated with either 5-HT hypofunctionality
      or hyperfunctionality reveals a major weakness in the OCD spectrum theory, i.e.
      that the associations between obsessive-compulsive behaviours and 5-HT
      abnormalities are less specific than suggested by the original obsessive
      compulsive spectrum model.

PMID- 11448085
TI  - Comparative study of mortality rates and cardiac dysrhythmias in post-marketing
      surveillance studies of sertindole and two other atypical antipsychotic drugs,
      risperidone and olanzapine.
AB  - Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspended in
      the European Union in 1998 following regulatory concerns over reports of serious
      cardiac dysrhythmias and sudden unexpected deaths. The reported causes of death,
      their frequency, prolongation of the rate corrected QT interval (QTc) and cardiac
      dysrhythmias in patients prescribed sertindole were compared with those for
      patients treated with two other atypical antipsychotics. All patients in England,
      prescribed atypical antipsychotics by general practitioners during each drug's
      immediate post-marketing period, were identified using an observational cohort
      technique, prescription-event monitoring. Mortality rates in the sertindole
      cohort were compared with those in a comparator cohort using standardized
      mortality ratios and incidence rate ratios. Cardiovascular events were reviewed
      and followed up to identify cases of prolongation of QTc interval. There was no
      statistically significant difference in mortality rates between sertindole and
      the comparator cohort, although confidence intervals (CI) were wide due to small
      numbers in the sertindole cohort. A much smaller number of patients were
      prescribed sertindole than the other antipsychotics. Six cases of prolongation of
      QTc interval were identified in 462 patients (1.3%, 95% CI 0.5-2.8) treated with
      sertindole and one with unspecified electrocardiogram changes in the comparator
      cohort of 16,542 patients. This study contributes to the understanding of the
      occurrence of prolongation of QTc interval during clinical use of sertindole, the
      incidence of which was similar to that in clinical trials. Although no
      statistically significant difference was shown in mortality rates between
      sertindole and comparator cohort, the sertindole cohort was too small to rule out
      an association between the use of this drug and cardiovascular deaths.

PMID- 11448086
TI  - Suicide and schizophrenia.
AB  - Suicide and suicide attempts occur at a significantly greater rate in
      schizophrenia than in the general population. Common estimates are that 10% of
      people with schizophrenia will eventually have a completed suicide, and that
      attempts are made at two to five times that rate. Demographically associated with
      suicidality in schizophrenia are being young, being early in the course of the
      illness, being male, coming from a high socioeconomic family background, having
      high intelligence, having high expectations, not being married, lacking social
      supports, having awareness of symptoms, and being recently discharged from the
      hospital. Also associated are reduced self-esteem, stigma, recent loss or stress,
      hopelessness, isolation, treatment non-compliance and substance abuse.
      Clinically, the most common correlates of suicidality in schizophrenia are
      depressive symptoms and the depressive syndrome, although severe psychotic and
      panic-like symptoms may contribute as well. This review specifically explores the
      issue of depression in schizophrenia, in relation to suicide, by organizing the
      differential diagnosis of this state and highlighting their potentially treatable
      or correctable causes. This differential diagnosis includes both acute and
      chronic disappointment reactions, the prodrome of an acute psychotic episode,
      neuroleptic induced akinesia and akathisia, the possibility of direct neuroleptic
      induced depression, negative symptoms of schizophrenia, and the possible co
      occurrence of an independent depressive diathesis. The potential beneficial roles
      of 'atypical' antipsychotic agents, including both clozapine and more novel
      agents, and adjunctive treatment with other psychopharmacological medications are
      considered, and the important roles of psychosocial factors and interventions are
      recognized.

PMID- 11448087
TI  - The 'dalhousie serotonin cocktail' for treatment-resistant major depressive
      disorder.
AB  - We describe the successful treatment of five patients with treatment-resistant
      major depressive disorder (TR-MDD) with a combination pharmacotherapy of
      pindolol, tryptophan and nefazodone. Five TR-MDD outpatients who had previously
      not responded to at least four different antidepressant medication trials were
      initiated on 300 mg/day of nefazodone, 7.5 mg/day of pindolol and 1 g/day of
      tryptophan. Pindolol doses remained the same throughout the 20 weeks, while
      tryptophan and nefazodone dosages were gradually increased to 8 g/day and 450
      mg/day, respectively. The Hamilton Depression Rating Scale (HAM-D) was used to
      evaluate outcome. By week 4, all cases demonstrated at least 50% decrease in HAM
      D scores. At the end of the trial, the group mean HAM-D score had significantly
      decreased from 26.8 (+/- 1.9) to 1.8 (+/- 0.8) (p < 0.001). No significant
      adverse effects were reported. These results suggest that if serotonin
      availability and release is further enhanced by tryptophan in the presence of
      nefazodone and pindolol, an antidepressant effect may be produced in patients who
      are otherwise treatment-resistant. Due to limited sample size, an open design and
      an 'unusually' high successful efficacy rate of this preliminary study,
      controlled studies are required to confirm the efficacy of this treatment
      strategy.

PMID- 11448088
TI  - Antidepressant discontinuation (withdrawal) symptoms presenting as 'stroke'.
AB  - We report two patients who developed a severe discontinuation (withdrawal)
      reaction following stoppage of paroxetine and venlafaxine, respectively.
      Neurological symptoms were prominent and neither patient could walk unaided. Both
      patients feared they had suffered a 'stroke' and arranged an emergency medical
      consultation. One patient was correctly diagnosed, the antidepressant was
      recommenced and symptoms resolved within 24 h. Failure to recognize the reaction
      resulted in the other patient being referred to a neurologist, undergoing a
      computed tomography brain scan and an electroencephalogram and remaining
      symptomatic for over 8 weeks. Relevant pharmacological issues are discussed. The
      cases illustrate the importance of patients and clinicians being familiar with
      antidepressant discontinuation symptoms.

PMID- 11448089
TI  - Urinary retention caused after fluoxetine-risperidone combination.
AB  - A case of urinary retention emerging after fluoxetine (20 mg/day) addition to low
      risperidone doses (2 mg/day) is presented. Severe extrapyramidal side-effects
      (EPS) also occurred after fluoxetine-risperidone combination. Several
      possibilities, based on the pharmacodynamic and pharmacokinetic properties of
      risperidone and fluoxetine, which merit consideration in an attempt to explain
      our patient's side-effects, are discussed. Extrapyramidal side-effects can be due
      to an increase of the plasma concentration of risperidone and/or the intrinsic
      propensity of fluoxetine to produce EPS. Urinary retention may be the consequence
      of a central serotoninergic mechanism in, or without, combination central D2
      blockade.

PMID- 11448090
TI  - Effect of repeated methylphenidate administration on presynaptic dopamine and
      behaviour in young adult rats.
AB  - Methylphenidate, a dopamine reuptake inhibitor, is the most common treatment for
      attention-deficit hyperactivity disorder and may be prescribed for years, despite
      little evidence of any long-term benefit, nor knowledge of potential chronic side
      effects. Therefore, this study examined the acute and longer-term behavioural
      effects and assessed striatal dopamine function following subchronic
      methylphenidate administration to adolescent rats. Male hooded Lister rats
      received methylphenidate (4 mg/kg i.p. twice daily for 4 days) or saline (1
      ml/kg) and the acute locomotor and stereotype behaviour was monitored on days 1
      and 4, novel object exploration on day 2 and, following 12 days drug withdrawal,
      the long-term effect examined on social interaction on day 16. Ex-vivo K+ (20 mM)
      and methylphenidate (0.1 mM)-induced [3H]dopamine release from striatal slices
      and striatal monoamine content were measured on day 18. Compared with saline,
      methylphenidate induced mild hyperactivity without stereotypy but did not alter
      novel object exploration and, following withdrawal, had no long-term effect on
      social interaction. In striatal slices from controls, both K+ and methylphenidate
      elevated [3H]dopamine release (p < 0.01) while only combined treatment elevated
      release in methylphenidate pretreated rats, although striatal monoamine content
      was unaltered compared with control rats. In summary, a repeated dose of
      methylphenidate that had acute behavioural effects produced no long-term
      alteration in social interaction but attenuated presynaptic striatal dopamine
      function.

PMID- 11448091
TI  - Interactions between LY354740, a group II metabotropic agonist and the GABA(A)
      benzodiazepine receptor complex in the rat elevated plus-maze.
AB  - Flumazenil, a benzodiazepine (BZ) receptor antagonist, and naloxone, a non
      selective mu-receptor antagonist, were used to investigate whether the anxiolytic
      action of LY354740 [1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate
      monohydrate], a Group II metabotropic glutamate receptor agonist, was mediated
      through the benzodiazepine binding site on the GABA(A) receptor and opioid
      pathways. LY354740 (1.0-10.0 mg/kg i.p.) induced dose-dependent anxiolytic-like
      effects in the rat elevated plus-maze. The anxiolytic-like effects of LY354740
      (10.0 mg/kg) and the benzodiazepine receptor agonist, chlordiazepoxide (CDP, 5.0
      mg/kg i.p.) were blocked by flumazenil (15.0 mg/kg i.p.). By contrast, naloxone
      (10.0 mg/kg i.p.) failed to affect the anxiolytic-like effects of either LY354740
      or CDP. The behaviour of animals treated with flumazenil or naloxone alone did
      not significantly differ from that of animals treated with vehicle alone. This
      study suggests that the anxiolytic-like effects of LY354740 on the elevated plus
      maze may be directly or indirectly mediated by the benzodiazepine binding site on
      the GABA(A) receptor complex.

PMID- 11448092
TI  - Serotonergic depletion increases conditioned suppression to background stimuli in
      the rat.
AB  - Dark Agouti rats were lesioned by intra-ventricular injection of 5,7
      dihydroxytryptamine (DHT) and, 2 weeks later, learning was tested in a
      conditioned suppression of drinking procedure. Lesioned and vehicle-injected
      control rats were conditioned with a discrete stimulus (tone or light conditioned
      stimulus, CS) twice paired with footshock (unconditioned stimulus), with or
      without a 30-s trace interval between these events to produce strong and weak
      learning conditions (a trace conditioning effect). During this conditioning
      session, the alternate stimulus (light or tone) was presented continuously in the
      background. Since the 5,7-DHT lesion also reduced the baseline licking response
      in the experimental chambers, we used drinking during the first minute, when this
      non-specific effect was minimal, as the dependent variable. We tested
      conditioning to target CS and to the alternative experimental background stimulus
      in exactly the same way in the same rats. We found that a level of serotonergic
      depletion without any intrinsic action on the trace conditioning effect
      nevertheless increased conditioning to the alternative background stimulus,
      irrespective of trace interval or stimulus modality. Thus, for both light and
      tone stimuli, the effect of serotonergic depletion depended only on the discrete
      target versus diffuse background role of the stimulus in use. These findings have
      implications for the modification of human cognition by serotonergic drugs.

PMID- 11448093
TI  - Effect of naloxone therapy on depersonalization: a pilot study.
AB  - To test the hypothesis of the role for the opioid system in the pathogenesis of
      depersonalization, the effect of naloxone (an opioid receptor blocker) on the
      symptoms and corticosteroids secretion was studied in patients with
      depersonalization syndrome. Fourteen depersonalization patients were treated with
      naloxone: 11 patients received single doses (1.6 or 4 mg i.v.) and three others
      received multiple infusions, with the maximal dosage being 10 mg, and the effect
      of naloxone on symptom severity was determined. In eight patients, the cortisol,
      cortisone and corticosterone content in the blood plasma was determined prior to
      and after the 4 mg naloxone infusion. A reversed-phase microcolumn high
      performance liquid chromatography with ultraviolet detection was applied for
      assessment of glucocorticoids. In three of 14 patients, depersonalization
      symptoms disappeared entirely and seven patients showed a marked improvement. The
      therapeutic effect of naloxone provides evidence for the role of the endogenous
      opioid system in the pathogenesis of depersonalization.

PMID- 11448094
TI  - The differential effects of chlorpromazine and haloperidol on latent inhibition
      in healthy volunteers.
AB  - Latent inhibition (LI) is a measure of reduced learning about a stimulus to which
      there has been prior exposure without any consequence. It therefore requires a
      comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition.
      Since, in animals, LI is disrupted by amphetamines and enhanced by
      antipsychotics, LI disruption has been proposed as a measure of the
      characteristic attentional deficit in schizophrenia: the inability to ignore
      irrelevant stimuli. The findings in humans are, however, inconsistent. In
      particular, a recent investigation suggested that since haloperidol disrupted LI
      in healthy volunteers, and LI was normal in non-medicated patients with
      schizophrenia, the previous findings in schizophrenic patients were entirely due
      to the negative effects of their medication on LI (Williams et al., 1998). We
      conducted two studies of antipsychotic drug effects on auditory LI using a within
      subject, parallel group design in healthy volunteers. In the first of these,
      single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg
      p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared
      with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test
      performance (spatial working memory (SWM), Tower of London and intra/extra
      dimensional shift, from the CANTAB test battery) and visual analogue rating
      scales, were also included as other measures of attention and frontal lobe
      function. Haloperidol was associated with a non-significant reduction in LI
      scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters
      of the subjects. The LI finding may be explained by increased distractibility
      which was indicated by an increase in antisaccade directional errors in this
      group. In contrast, LI was significantly increased by chlorpromazine but not by
      an equally sedative dose of lorazepam (both drugs causing marked decreases in
      peak saccadic velocity). Paroxetine had no effect on LI, eye movements or CANTAB
      neuropsychological test performance. Haloperidol was associated with impaired
      SWM, which correlated with the degree of dysphoria/akathisia, but no other drug
      effects on CANTAB measures were detected. We conclude that the effect of
      antipsychotics on LI is both modality and pharmacologically dependent and that
      further research using a wider range of antipsychotic compounds is necessary to
      clarify the cognitive effects of these drugs, and to determine whether there are
      important differences between them.

PMID- 11448095
TI  - Pigpen and endothelial cell differentiation.
AB  - Endothelial cells can toggle back and forth between differentiated and relatively
      undifferentiated states with comparative ease. This is an important
      characteristic, particularly in adult tissues where the constitutive endothelial
      cell phenotype is quiescent. It enables rapid repair of wounds, renewal of the
      vascular intima in parts of the circulatory system with high flow and turbulence,
      and is essential to the cyclic function of reproductive organs. However, the
      ability to dedifferentiate can be a severe disadvantage when it is subverted to
      the support of disease processes such as tumor growth and metastasis. The control
      of endothelial cell differentiation state is, therefore, a matter of significance
      to investigators of basic developmental mechanism, as well as those studying an
      array of neovascular disorders. Recently, studies have advanced beyond the
      identification of extracellular triggers and overt cellular responses to the
      analysis of signal transduction pathways and nuclear events. This review focuses
      on the nuclear protein pigpen that is found in the right place at the right time,
      and with the necessary equipment, to modulate endothelial cell differentiation.
      We project that when we better understand the relationship of pigpen to its
      upstream regulators and downstream effectors, we will also have a better
      understanding of the mechanisms underlying capillary morphogenesis.

PMID- 11448096
TI  - Hepatic regeneration induces transient acute phase reaction: systemic elevation
      of acute phase reactants and soluble cytokine receptors.
AB  - The growth factors present during liver regeneration partially overlap with the
      regulators of the hepatic acute phase response. We analysed the acute phase
      reaction and changes in soluble cytokine receptors after partial hepatectomy,
      when tissue injury inducing acute phase reaction and major reduction of liver
      mass occur simultaneously. Three acute phase proteins and mRNAs were determined
      by ELISA and northern blot hybridisation in rats. Serum levels of IL-6 and three
      soluble cytokine receptors (sTNF-alpha R I and II, sIL-6R) were detected by ELIBA
      or dot-blot assay. Time-course profiles of fibrinogen, alpha(2)-macroglobulin and
      haptoglobin proteins and mRNA are presented. Elevation of IL-6, soluble TNF-alpha
      receptors and soluble IL-6 receptor levels were also detected. The time-course of
      changes in haptoglobin concentration and elevation of soluble cytokine receptors
      is described by this in vivo experimental system. The results show good
      correlation with (post)transcriptional activation of immediate and delayed early
      gene products. These data suggest the involvement of both acute phase proteins
      and soluble cytokine receptors in the regulation of liver regeneration.

PMID- 11448097
TI  - Direct nitric oxide imaging in cultured hippocampal neurons with
      diaminoanthraquinone and confocal microscopy.
AB  - A method for the direct measurement of intracellular nitric oxide (NO) production
      stimulated by penicillin G (PG) in cultured hippocampal neurons with
      diaminoanthraquinone (DAA) using laser scanning confocal microscopy (LSCM) was
      developed. Intracellular DAA fluorescence could specifically represent NO
      production based on two facts: (1) 3-morpholinosydnonimine, a NO donor, could
      dose-dependently increase DAA fluorescence; and (2) haemoglobin, a NO scavenger,
      could inhibit the increase of DAA fluorescence. The PG dose-dependently increased
      the intercellular level of glutamate (Glu, 5 min after stimulation) and the
      intracellular NO production (30 min throughout stimulation). The increase of NO
      production could be reversed by N(w)-nitro- l -arginine (a NO synthase
      inhibitor), and also by d (-)2-amino-5-phosphonovaleric acid, a subtype of Glu
      receptor antagonist. These results revealed that DAA could be used to indicate
      real-time and kinetic intracellular NO production of hippocampal neurons with
      higher sensitivity, specificity and accuracy.

PMID- 11448098
TI  - Apoptotic and mitotic activity in squamous cell carcinoma cells after combined
      modality treatment with gamma-irradiation and dibromodulcitol.
AB  - A-431 squamous cell carcinoma cells were treated in vitro with either 4 Gy
      radiation of 15 (or 45) microg/ml dibromodulcitol (DBD), as well as with combined
      4 Gy irradiation and DBD, with the latter as either a pretreatment or post
      treatment. DBD alone or in combination with radiation had a greater effect on
      cell proliferation than the effect of radiation alone. The difference is due to a
      higher level of apoptosis induced by DBD, especially in conjunction with
      radiation. Such a combination may therefore be useful in the treatment of
      squamous cell carcinoma, which in general responds poorly to radiation therapy.

PMID- 11448099
TI  - Purification and identification of a human dermal extract component inhibitory to
      fibroblast proliferation.
AB  - It was previously shown that a citric acid buffer extract of human dermis
      (extract D) inhibited growth of human diploid fibroblasts in monolayer culture
      (Muir et al., 1997). Further fractionation has shown that the active principle is
      probably a proteoglycan, and that retention of its inhibitory activity is
      dependent on the use protease inhibitors throughout the extraction procedure.
      Elution of extract D from a DEAE-cellulose column produced four major peaks, each
      of which was subjected to SDS-PAGE as well as being tested for inhibitory
      activity on the growth of fibroblasts in culture. Peaks III and IV had no
      inhibitory effect, but peak I contained highly active material. Gels of this peak
      showed prominent bands of 120 kDa (corresponding to dermatan sulphate
      proteoglycan II, DS-PG II) and at 45 kDa (corresponding to the core protein). The
      latter band became more prominent when extract D which had been treated with
      chrondroitinase ABC was electrophoresed. Their identities were verified by
      Western blotting. Peak II also contained some slower-acting inhibitory material
      which has as yet to be identified, but contains little or no protein
      corresponding to the decorin core-protein. The data indicate that the intact
      decorin molecule, DS-PG II, is the main inhibitory principle in human skin.

PMID- 11448100
TI  - Cytostatic effect of inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2
      diacyl-sn-glycerol (CDP-DG): inositol transferase, on oral squamous cell
      carcinoma cell lines.
AB  - Inostamycin, which was recently isolated from Streptomyces sp. MH816-AF15 as an
      inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol
      transferase, caused a G1-phase accumulation in the cell cycle of small cell lung
      carcinomas. To investigate whether the cytostatic effect of inostamycin is
      restricted to lung carcinoma cell lines or applicable to other type of cells, we
      tested five oral squamous cell carcinoma (SCC) cell lines. Cell growth was
      suppressed in 62.5--125 ng/ml inostamycin in the culture medium in all oral
      cancer cell lines tested, with non-viable cells being <1%, indicating inostamycin
      is cytostatic on SCC cell lines. Decrease in cyclin D1 mRNA and protein
      expression due to the inostamycin treatment was accompanied by suppression of
      phosphorylated retinoblastoma susceptibility gene product (pRB-P) levels.
      Moreover, flow cytometric analysis showed that inostamycin induced an increase in
      G1/G0 cells (1.2--3.2 fold) over 24 h. These results suggest that inostamycin is
      a useful agent for tumour dormant cytostatic therapy for oral SCC.

PMID- 11448101
TI  - Growth inhibition and differentiation of C6 glioma cells on treatment with hmba.
AB  - HMBA, a differentiation inducer belonging to the class of hybrid polar compounds,
      is known to induce terminal differentiation of a number of leukemic and solid
      tumour cell lines. In this report we have shown that HMBA markedly inhibits
      growth of C6 glioma cells at non-cytotoxic concentrations ranging from 2.5 m m to
      10 m m in a dose-dependent manner. The growth inhibitory effect can be detected
      as early as 18--24 h. By the sixth day the growth inhibition decreases at all the
      concentrations tested. Treatment with HMBA results in an accumulation of C6 cells
      in G0/G1 phase along with a decrease in the number of cells in S phase. HMBA
      induces morphological differentiation of C6 cells and increases expression of
      glial fibriliary acidic protein (GFAP), a marker for mature astrocytes. HMBA
      induces c-fos and represses cycloheximide-induced c-jun and fra-1 expression.
      HMBA-induced growth inhibition of C6 cells is accompanied by a decrease in Cdk4
      protein levels. However, HMBA fails to sustain low Cdk4 levels, which may be
      responsible for HMBA's failure to sustain the growth inhibitory effect.

PMID- 11448102
TI  - Cloning, sequencing and expression of a cDNA encoding the mouse L35a ribosomal
      protein during differentiation of murine erythroleukemia (MEL) cells.
AB  - In a previous study we reported that ribosomal protein S5 gene is suppressed in
      differentiating and not in proliferating or apoptotic murine erythroleukaemia
      (MEL) cells (Vizirianakis et al., 1999). We wish to report here the isolation,
      characterisation and expression of the full length cDNA for another ribosomal
      protein, the L35a (rpL35a), in MEL cells. This cDNA shares significant structural
      homology in both DNA and protein levels to genes encoding the rat and human L35a
      ribosomal proteins. Northern blot hybridisation analysis has shown that the
      steady-state level of rpL35a mRNA is progressively reduced during differentiation
      of MEL cells along the erythrocytic maturation pathway induced by DMSO or UDP-4,
      two structurally unrelated inducers of differentiation. However, in cells where
      differentiation was inhibited by N(6)-methyladenosine, the level of rpL35a RNA
      transcripts was not affected. In addition, rpL35a gene expression was not altered
      in apoptotic MEL cells. Furthermore, the suppression of L35a gene was not
      correlated to any change in DNA methylation at CCGG sites located at the rpL35a
      gene locus in undifferentiated and differentiated MEL cells, as we observed for
      the rpS5 gene. Overall, these data suggest that the expression of ribosomal
      genes, the L35a of 60S ribosomal subunit and the S5 of 40S ribosomal subunit, are
      regulated by a common mechanism in differentiating MEL cells, leading to the
      observed decrease in ribosomal function.

PMID- 11448103
TI  - Inhibition of the contraction of collagen gels by extracts from human dermis.
AB  - Extracts from the human dermis were prepared and evaluated with respect to their
      ability to influence fibroblasts to contract collagen gels in vitro. The extract
      which had the most inhibitory effect on fibroblasts to cause contraction of
      collagen gels was extract D. It also inhibited fibroblast growth. Inhibition of
      contraction was not simply related to fibroblast cell numbers and the data
      suggests a specific effect upon the ability of fibroblasts to cause contraction.
      Other extracts were without significant effect.

PMID- 11448104
TI  - Cell type-dependent collagen-type recognition by cell receptors.
AB  - Affinity chromatography of a number of cell types on collagens I and III reveals
      three proteins with M(R)of 250, 170 and 140 kDa. These proteins are able to
      discriminate between types I and III, but not types III and IV. Collagen-type
      recognition is therefore characteristic for cells of connective tissue origin.
      Polyclonal antibodies (Ab) raised against 170 and 140 kDa polypeptides and used
      in immunofluorescence show membrane localisation for both, with their
      distribution being similar to each other and to the distribution of the integrin
      beta1 chain. Ab p140 and commercial monoclonal antibodies against alpha(2)chain
      stain a band of the same molecular mass as from purified collagen binding
      proteins from liver cells, indicating that the 140 kDa protein is probably the
      alpha(2)integrin chain. The alpha(2)chain containing integrins are therefore able
      to discriminate collagen types I and III and collagen type recognition by this
      receptor is cell-type dependent.

PMID- 11448105
TI  - Hydrostatic pressure induced changes in the cytoarchitecture of pheochromocytoma
      (PC-12) cells.
AB  - Confocal microscopy, in association with three-dimensional reconstruction,
      revealed that microtubules and microfilaments in differentiating PC-12 cells were
      disrupted in a dose-dependent manner following pressure treatment. Hydrostatic
      pressure caused cell rounding, microtubule and microfilament disorganization,
      neurite retraction and the formation of a microtubule ring adjacent to the cell
      surface. Volume analysis from computer-generated reconstructed cells, at
      atmospheric pressure, showed that the apparent volume of microtubules and
      microfilaments, normalized to 100 units, was 22 and 11 respectively. At 4000 and
      8000 psi, the apparent microtubule volume was reduced to 16 and 12 units,
      respectively, and the apparent microfilament volume was reduced to 8 and 5 units,
      respectively. Thus, the apparent microtubule and microfilament volumes in PC-12
      cells decreased as pressure increased. In the presence of taxol and phalloidin
      which stabilize the cytoarchitecture, cells resist the effects of hydrostatic
      pressure. In the presence of colchicine and cytochalasin D compounds which
      destabilize the cytoarchitecture, cells are more susceptible to the disrupting
      effects of hydrostatic pressure. The effects of hydrostatic pressure on cell
      morphology were reversible.

PMID- 11448106
TI  - The effects of hydrostatic pressure-induced changes on the cytoskeleton and on
      the regulation of gene expression in pheochromocytoma (PC-12) cells.
AB  - The purpose of this investigation was to determine the relationship of
      hydrostatic pressure-induced changes in the cytoarchitecture to regulation of
      gene expression in PC-12 cells. Hydrostatic pressure disrupts the cytoskeleton,
      decreases tubulin and actin mRNA levels and causes changes in the localization of
      tubulin and actin mRNA. Actin mRNA levels, at 6000 and 10,000 psi for 20 min,
      were reduced to 78% and 64%, respectively, in undifferentiated cells and to 81%
      and 72%, respectively, in 4-day differentiating cells, relative to untreated
      controls. Tubulin mRNA levels, at 6000 and 10,000 psi for 20 min, were reduced to
      75% and 67%, respectively, in undifferentiated cells and to 84% and 74%,
      respectively, in 4-day differentiating cells. Changes in the localization of mRNA
      in the soluble and cytoskeletal fractions were determined by measuring the
      pressure level where the mRNA level in the cytoskeletal fraction equals the mRNA
      level in the soluble fraction. This measurement was designated the
      cytoskeletal/soluble fraction index (CSFI(50)). CSFI(50)measurements indicated
      that following hydrostatic pressure, actin mRNA cytoskeletal association was more
      stable than tubulin mRNA cytoskeletal association. The addition of chemicals
      which stabilize or destabilize microtubules and microfilaments to pressure
      treatment resulted in additional changes in the CSFI(50).

PMID- 11448107
TI  - Regulation of gelatinase-A (MMP-2) production by ovine intervertebral disc
      nucleus pulposus cells grown in alginate bead culture by Transforming Growth
      Factor-beta(1)and insulin like growth factor-I.
AB  - The aim of this study was to gain information relevant to disc repair processes.
      Limited degradation of the collagen matrix by matrix metalloproteases (MMPs) may
      facilitate the loosening of cell-cell and cell-matrix interactions within the
      injured intervertebral disc (IVD) to favour the penetration of blood vessels and
      migration of fibroblasts into the defect to promote repair processes. Gelatinase
      A (MMP-2) has a particularly important role to play in angiogenesis, in the
      present study we investigated the in vitro regulation of MMP-2 by Transforming
      Growth Factor-beta 1 (TGF-beta 1) and Insulin-like Growth Factor-1 (beta IGF-I)
      in cells from the nucleus pulposus (NP) of the ovine IVD. Ovine NP cells were
      grown in alginate bead cultures in complete medium (10% foetal calf serum) for 7
      days, established in serum-free conditions for 24 h, then stimulated with TGF
      beta 1 (0.1 or 10 ng/ml) or IGF-I (2 or 50 ng/ml) +/-Concanavalin A (20
      microg/ml) for an additional 48 h. Conditioned medium was examined for matrix
      metalloproteases using gelatin zymography, Tissue Inhibitor of Metalloproteinase
      2 (TIMP-2) and Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) were
      immunolocalised in beads. Pro (72 kDa) and active (59 kDa) MMP-2 were the major
      gelatinolytic MMPs detected in control cultures, the TGF-beta 1 and IGF-I
      treatments significantly decreased levels of the active MMP-2, inclusion of
      Concanavalin A resulted in a complete reversal of this trend with IGF-I, and to a
      lesser extent with TGF-beta 1. Cell surface levels of TIMP-2 and MT1-MMP were
      decreased by the TGF-beta 1 treatment while IGF-I only appeared to decrease TIMP
      2 expression. The findings of this study provide some insight as to why dense
      avascular connective tissues such as the intervertebral disc have such a poor
      healing potential.

PMID- 11448108
TI  - Potassium concentration is reduced in cultured rabbit tracheal smooth muscle
      cells after withdrawal of serum.
AB  - Comparison of elemental concentrations in growth-arrested airway smooth muscle
      cells with those in their proliferating counterpart showed that potassium (K(+))
      was significantly reduced, whereas concentrations of other elements sodium
      (Na(+)), magnesium (Mg(2+)), phosphorus (P), and chlorine (Cl(-)) remained
      unchanged. Reduced K(+)concentration was associated with a change in the cells
      from a spindle shape to a flattened form.

PMID- 11448109
TI  - Alternative splicing of Rh blood group polypeptide mRNA produces a novel
      transcript containing a short nucleotide insertion on human erythroleukemia K562
      cells.
AB  - A novel isoform of the human Rh blood group polypeptide cDNA was isolated from
      human erythroleukemic K562 cells. This isoform was produced by deletion of the
      sequences derived from exons 2 and 3 of the RHCE gene and insertion of 44-bp into
      the resulting junction between exon 1 and 4 derived sequence. The deduced amino
      acid sequence revealed that the 44-bp insertion sequence contains an in-frame
      stop codon that causes premature chain termination. A sequence homology search
      using GenBank showed that the inserted sequence was derived from the intron
      between exons 1 and 2 of the RHCE gene. Moreover, analysis of the region
      surrounding the inserted sequence indicated that the insert was a cryptic exon
      flanked by consensus donor and acceptor splice sequences. This novel transcript
      was most likely produced by alternative splicing.

PMID- 11448110
TI  - Human platelets loaded with trehalose survive freeze-drying.
AB  - Human blood platelets are stored in blood banks for 5 days, after which they are
      discarded, by federal regulation. This short lifetime has led to a chronic
      shortage of platelets, a problem that is particularly acute in immunosuppressed
      patients, such as those with AIDS. We report here that platelets can be preserved
      by freeze-drying them with trehalose, a sugar found at high concentrations in
      organisms that naturally survive drying. We suggest that these findings will
      obviate the storage problem with platelets. Trehalose is rapidly taken up by
      human platelets at 37 degrees C, with loading efficiencies of 50% or greater.
      Fluid-phase endocytosis plays an important role in this efficient uptake of
      trehalose, but other mechanisms may also be involved. Trehalose-loaded platelets
      were successfully freeze-dried, with excellent recovery of intact platelets.
      Rehydration from the vapor phase led to a survival rate of 85%. The response of
      these platelets to the agonists thrombin (1 U/ml), collagen (2 microg/ml), ADP
      (20 micromM), and ristocetin (1.6 mg/ml) was almost identical to that of fresh,
      control platelets. Analysis by Fourier transform infrared spectroscopy
      demonstrated that the membrane and protein components of trehalose-loaded
      platelets after freeze-drying, prehydration, and rehydration were remarkably
      similar to those of fresh platelets.

PMID- 11448111
TI  - Factors affecting leakage of trapped solutes from phospholipid vesicles during
      thermotropic phase transitions.
AB  - Liposomes are commonly used as models for chilling and freezing damage, with
      leakage of water-soluble contents from the aqueous interior as the most
      frequently used measurement of damage. In order to achieve an understanding of
      the mechanism of the leakage, we have conducted a study of the factors that
      influence the leakage from liposomes during phase transitions. While such
      investigations have appeared sporadically in the literature, a detailed study has
      not been undertaken previously, despite the fact that liposomes are widely used
      as models for stress injury. Thus, we suggest that these findings will be of
      general interest in the cryobiology community. We now report that the following
      variables affected leakage from liposomes during chilling: (i) increasing the
      rate of cooling and warming resulted in decreased leakage; (ii) maximal leakage
      occurred at the measured phase transition temperature; (iii) addition of defect
      forming additives such as a second phospholipid or a surfactant increased leakage
      from the liposomes during the phase transition but not above or below that
      temperature; (iv) small unilamellar vesicles leaked much more rapidly than large
      unilamellar vesicles; and (v) increasing the pH of the external buffer decreased
      leakage of carboxyfluorescein, an effect that is probably particular to ionizable
      solutes.

PMID- 11448112
TI  - Vitrification of mouse oocytes in ethylene glycol-raffinose solution: effects of
      preexposure to ethylene glycol or raffinose on oocyte viability.
AB  - We investigated the effects of preexposure to ethylene glycol (EG) or raffinose
      on the viability of vitrified mouse oocytes. Ovulated oocytes at the metaphase II
      stage were preexposed either to 2 M EG for 0, 2, or 5 min or to ascending
      concentrations (0.15 followed by 0.3 M ) of raffinose solution for 2, 5, or 10
      min each (here referred to as 2-2, 5-5, and 10-10 min, respectively). The oocytes
      were then exposed to a vitrification solution (VS), 6 M EG + 0.3 M raffinose, for
      0.5, 1, 2, or 5 min and then vitrified or immediately diluted. After warming, the
      developmental capacity of oocytes was determined after in vitro fertilization.
      Volume changes in oocytes during preexposures and exposure to the VS were also
      investigated. The results demonstrated that preexposure to 2 M EG allowed shorter
      exposure times of oocytes to the VS and that predehydration in raffinose
      solutions for 5-5, but not 2-2 or 10-10 min, allowed a wider range of exposure
      times to the VS. Experiments on volume change suggested that the optimum time of
      exposure to the VS depends on the amount of EG permeation after preexposure to 2
      M EG or to raffinose solutions. Preexposures to 2 M EG or raffinose under
      optimized conditions increased the viability of vitrified-warmed oocytes compared
      to direct exposure to VS without preexposures.

PMID- 11448113
TI  - Low temperature storage of larvae and synchronization of adult emergence in the
      predatory midge Aphidoletes aphidimyza.
AB  - Diapause larvae of Aphidoletes aphidimyza were stored at a temperature of 3
      degrees C under continuous darkness for up to 7 months with survival rates above
      50%; after storage for 1 year the survival rate dropped to 12%. Diapause was
      terminated in the majority of individuals within 120 days of chilling under
      storage conditions. Brief exposure (10-60 s) to the vapor of n-hexane appeared to
      be a useful alternative to chilling for the termination of diapause. The larvae
      with terminated diapause required, on average, an additional 31 days at 22
      degrees C and long-day conditions in order to reach the adult stage. The 10-90%
      adult emergence spanned a period of 21.1 days. When the larvae with terminated
      diapause were exposed to 30 degrees C for 1 week after the end of low temperature
      storage, the survival rate was not affected, the average "time-to-adult"
      shortened moderately to 28 days, and the synchrony of adult emergence improved
      considerably to 10 days. Low temperature storage of nondiapause larvae resulted
      in a decrease in survival from 98 to 31% during the first 60 days of storage.
      Nondiapause larvae did not enter diapause during low temperature storage and, as
      a consequence, the adults emerged relatively rapidly (after 14-15 days) and
      synchronously (within 2-3 days) after the end of storage. Directions for future
      research, which might bring further improvement in low temperature storability
      and synchrony of adult emergence in A. aphidimyza, are proposed.

PMID- 11448114
TI  - Cryopreservation of mouse ovarian tissue following prolonged exposure to an
      Ischemic environment.
AB  - In cases in which ovarian tissue is to be cryopreserved for tissue or gene
      banking it is important to maintain its integrity and viability. This study
      examined how delays between the death of an animal and the
      collection/cryopreservation of its ovarian tissue influenced follicle viability.
      Mouse ovaries were placed in PBS+antibiotic (in vitro) or left within the body
      (in situ) at room temperature for 0, 3, 6, 12, or 24 h following the death of the
      donor. These ovaries were cryopreserved at 1 degrees C/min on dry ice or in a -84
      degrees C freezer using a passive cooling device or by conventional slow cooling
      (0.3 degrees C/min). The ovaries were grafted under the kidney capsule of
      ovariectomized recipient mice and collected 2 weeks later, and the size and
      number of follicles were determined. Cryopreserved ovarian tissue grafted
      immediately after the death of the donor contained numerous viable and healthy
      follicles independent of the cooling procedure (dry ice, 134 +/- 32; -84 degrees
      C, 165 +/- 54; slow, 214 +/- 55 follicles per half ovary). Tissues stored in
      vitro before cryopreservation retained viable follicles up to 12 h after death
      (dry ice, 30 +/- 15; -84 degrees C, 86 +/- 45; slow, 93 +/- 33), whereas tissue
      left in situ had significantly reduced follicle numbers within 3 h of death (dry
      ice, 36 +/- 12; -84 degrees C, 19 +/- 6; slow, 28 +/- 7). No significant
      difference was found between the cooling rates tested, indicating that a passive
      cooling container which cools at 1 degrees C/min is a suitable alternative to
      conventional slow cooling. We conclude that ovarian tissues for cryobanking
      should be cryopreserved as soon as possible after collection or death of the
      animal to ensure maximal follicular survival.

PMID- 11448115
TI  - The effect of prefreezing the diluent portion of the straw in a step-wise
      vitrification process using ethylene glycol and polyvinylpyrrolidone to preserve
      bovine blastocysts.
AB  - A total of 678 bovine blastocysts, which had been produced by in vitro
      maturation, fertilization, and culture, were placed into plastic straws and were
      vitrified in various solutions of ethylene glycol (EG) + polyvinylpyrrolidone
      (PVP). Part of the straw was loaded with TCM199 medium + 0.3 M trehalose as a
      diluent; the diluent portions of the straw were prefrozen to either -30 or -196
      degrees C. Then, the embryos suspended in the vitrification solution were
      pipetted into the balance of the straw and vitrified by direct immersion into
      liquid nitrogen. For thawing, the straws were warmed for 3 s in air and 20 s in a
      water bath at 39 degrees C and then agitated to mix the diluent and
      cryoprotectant solution for 5 min followed by culture in TCM199 + 10% FCS + 5 +
      microg/ml insulin + 50 microg/ml gentamycin sulfate for 72 h. Variables that were
      examined were the time of exposure to EG prior to vitrification, the PVP
      concentration, and the temperature of exposure to EG + PVP prior to
      vitrification. Survival and hatching rates of the blastocysts exposed to 40% EG
      in four steps at 4 degrees C were higher than those of embryos exposed in two
      steps (81.3 +/- 4.3% and 80.2 +/- 3.4% vs 67.6 +/- 4.5% and 71.5 +/- 4.7%,
      respectively; P < 0.05). The same indices were superior following vitrification
      thawing of the blastocysts in 40% EG + 20% PVP than it was in 40% EG + 10% PVP
      (76.1 +/- 5.5% vs 63.7 +/- 1.8%; P < 0.05; and 61.6 +/- 6.0% vs 70.5 +/- 4.7%; P
      < 0.01, respectively). Exposure to the vitrification solution (40% EG + 20% PVP)
      at higher temperatures (37.5 degrees C vs 4 degrees C) reduced both survival and
      hatching rates (45.8 +/- 6.9% vs 83.9 +/- 4.4% and 41.5 +/- 1.8% vs 64.0 +/-
      4.7%, respectively; P < 0.001). These results indicate that blastocysts vitrified
      after prefreezing the diluent portions of the straws do favor developmental
      competence of in vitro produced embryos.

PMID- 11448116
TI  - Vitrification of large quantities of immature bovine oocytes using nylon mesh.
AB  - Vitrification of oocytes and embryos has recently been improved using new
      physical supports such as electron microscope (EM) grids, open-pulled straws, and
      cryoloops. However, the number of samples per container was restricted in each of
      these methods. In the present study, to develop a novel simple technique for
      vitrification of large quantities of oocytes or embryos, we examined
      vitrification of large quantities of immature bovine oocytes using nylon mesh as
      a novel container. As many as 65 oocyte-cumulus cell complexes could be placed on
      nylon mesh for vitrification compared with 15 per EM grid. Recovery rates were
      higher when using nylon mesh than EM grids, while fertilization and development
      rates were not different. These results indicated that vitrification using nylon
      mesh is useful and offers a new way to cryopreserve large numbers of oocytes.

PMID- 11448117
TI  - Three-dimensional morphological analysis of antigen-antibody reaction in hepatic
      sinusoids preserved in hypothermic UW solution.
AB  - ICAM-1 antigen-antibody reaction was visualized by three-dimensional
      immunoscanning electron microscopy of hepatic sinusoids in rat liver treated with
      hypothermic University of Wisconsin (UW) organ preservation solution. The results
      were compared with similar antigen-antibody reactions carried out with
      immunoliposomes injected in vivo. Morphologically, the hepatic sinusoids were
      preserved well during the hypothermic procedure. Endothelial cells had a large
      number of fenestrations, which partly aggregated and formed sieve plates. ICAM-1
      expression was induced by injection of LPS and detected by monoclonal antibody in
      the UW solution followed by gold-labeled secondary antibody. ICAM-1 was
      restricted mostly to the unique areas of sieve plates with immature, small
      fenestrations. A similar distribution of ICAM-1 was present when detected by in
      vivo injection of immunoliposomes containing the monoclonal ICAM-1 antibody. The
      results showed that antigen-antibody reactions can take place in livers preserved
      in hypothermic UW solution. Further, the reaction is similar to that which could
      occur in vivo during transplantation. This suggests that it may be possible to
      block potentially harmful antigen-antibody reactions by addition of appropriate
      antibodies to hypothermic UW solution prior to transplantation.

PMID- 11448118
TI  - Involvement of TRAIL/TRAIL-R interaction in IFN-alpha-induced apoptosis of Daudi
      B lymphoma cells.
AB  - Interferon-alpha (IFN-alpha) exerts the anti-tumour effect on various tumours at
      least partly through induction of apoptosis. Apoptosis is induced by members of
      the tumour necrosis factor (TNF) family, including Fas (CD95) and TNF-related
      apoptosis-inducing ligand (TRAIL). In the present study, we examined whether the
      TRAIL/TRAIL-R system is involved in IFN-alpha-induced apoptosis using Daudi B
      lymphoma cells. IFN-alpha upregulated the expression of TRAIL within 12 h, as
      assessed by flow cytometry and RT-PCR, and the level increased with time until 72
      h. The levels of both TRAIL-R1 and TRAIL-R2, low in Daudi cells, were enhanced by
      IFN-alpha. The enhanced TRAIL-R1/-R2 appeared to function as a death-inducing
      molecule since IFN-alpha-stimulated cells were more susceptible to TRAIL-induced
      cell death. The IFN-alpha-stimulated Daudi cells or their derived culture
      supernatants displayed cytotoxicity against TRAIL-sensitive, but not resistant
      lines. Moreover, the IFN-alpha-induced reduction in mitochondrial membrane
      potential preceding the induction of apoptosis was substantially prevented by
      neutralizing anti-TRAIL monoclonal antibody. Taken together, IFN-alpha-induced
      apoptosis appears to be mediated by the autocrine and/or paracrine loop involving
      TRAIL/TRAIL-R.

PMID- 11448119
TI  - Leukaemia inhibitory factor and interleukin 6 inhibit secretion of prolactin and
      growth hormone by rat pituitary MtT/SM cells.
AB  - The rat pituitary cell line, MtT/SM, has the characteristics of
      somatomammotrophs. The cells secrete both prolactin (PRL) and growth hormone
      (GH). We examined the effects of cytokines such as leukaemia inhibitory factor
      (LIF), interleukin 6 (IL-6), oncostatin M and interleukin 11 on the secretion of
      these hormones by the cells. These cytokines stimulate proliferation of the cells
      and inhibit the secretion of PRL by 70-80% and that of GH by 50%. They induce
      tyrosine phosphorylation of STAT3 in the cells. The cells containing PRL or GH
      decreased at 48 h after treatment of the cells with LIF or IL-6. These results
      suggest that the LIF/IL-6 family of cytokines inhibits the functions of
      mammotrophs and somatotrophs in the pituitary gland.

PMID- 11448120
TI  - Effects of long-term estrogen treatment on IFN-gamma, IL-2 and IL-4 gene
      expression and protein synthesis in spleen and thymus of normal C57BL/6 mice.
AB  - Estrogens have been shown to markedly modulate the immune system. One mechanism
      by which estrogens could modulate the immune system is by regulating cytokines,
      an aspect not well-studied thus far. To address this issue, normal C57BL/6
      orchiectomized mice were given estrogen and its effects on selected cytokines,
      interferon-gamma (IFN-gamma), interleukin 2 (IL-2) and IL-4 in lymphocytes from a
      developmental organ (thymus) and a mature lymphoid organ (spleen) examined.
      Estrogen significantly increased IFN-gamma and IL-2 mRNA in concanavalin-A (Con
      A) activated thymocytes, splenic lymphocytes, and in enriched splenic T cells.
      Estrogen had no marked effect on IL-4 mRNA. While estrogen increased IFN-gamma
      mRNA in Con-A activated unseparated splenic lymphocytes and enriched splenic T
      cells, a numerical increase in IFN-gamma was noticed only in the supernatants of
      Con-A activated unseparated splenic lymphocytes, but not in enriched splenic T
      cells. This suggests that for optimal secretion of IFN-gamma in estrogen-treated
      mice, co-stimulatory signals from antigen presenting cells are needed. Gender
      differences in IFN-gamma and IL-2 mRNA were also evident. Con-A activated splenic
      lymphocytes from gonadal-intact, untreated female had a pattern of numerical
      increase in IFN-gamma mRNA, and IFN-gamma and IL-2 protein levels compared to
      their male counterparts. Taken together, our data suggests that estrogens
      regulate the expression of cytokines, which could account in part, for the gender
      differences in immune capabilities.

PMID- 11448121
TI  - Interleukin 1 components in cicatricial pemphigoid. Role in intravenous
      immunoglobulin therapy.
AB  - Interleukin (IL-)1 is an important mediator of inflammatory responses and plays
      an important role in the pathogenesis of various autoimmune diseases. Cicatricial
      pemphigoid (CP) is a multisystem autoimmune inflammatory disease. We have studied
      the role of IL-1 in its pathogenesis. We have investigated the serum levels of IL
      1 components (IL-1alpha, IL-1beta, and IL-1Ra), and determined the role of
      intravenous immunoglobulin (IVIg) therapy in patients with CP. Serum levels of IL
      1alpha and beta were significantly higher in untreated patients with active
      disease compared to levels in patients in prolonged clinical remission and normal
      human controls (P<0.0001). The serum levels of IL-1Ra were higher in patients in
      prolonged clinical remission compared to patients with active disease (P=0.002).
      Hence elevated levels of IL-1alpha and beta and low levels of IL-1Ra correlate
      with disease activity. The levels of IL-1alpha and beta were statistically
      significantly higher in sera of CP patients with active disease pre-IVIg therapy
      compared to post-IVIg therapy (P<0.0001). Statistically significantly higher
      levels of IL-1Ra were present in post-IVIg treatment serum samples when compared
      to levels in pre-IVIg treatment (P<0.0001). In the in vitro experiments, the
      levels of IL-1alpha and beta produced by the peripheral blood mononuclear cells
      (PBMC) isolated from patients before IVIg therapy were significantly higher when
      compared to the PBMC isolated from post-IVIg patients (P<0.0001). Significantly
      higher levels of IL-1Ra were observed in the supernatants of PBMC collected from
      pre-IVIg patients and cultured with exogenously added IVIg, when compared to the
      levels of PBMC to which IVIg was not added (P<0.0001). IL-1 may be an important
      cytokine involved in the pathogenesis of CP. The regulation of IL-1 could be one
      of the mechanisms, amongst others, by which IVIg may exert its beneficial effect
      in the treatment of CP.

PMID- 11448122
TI  - Leptin receptor long-form signalling in a human liver cell line.
AB  - Expression of the long form of the leptin receptor was detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and Western blotting in the
      human liver cell line WRL68. Leptin (50-200 nM) significantly increased tyrosine
      phosphorylation of STAT cytoplasmic transcription factors STAT3 and STAT5b in a
      dose-dependent manner and produced a gel-shift with STAT3- and STAT5-specific
      oligonucleotides. WRL68 cells therefore provide the first human in vitro
      hepatocyte system in which to study leptin receptor-mediated signalling and to
      elucidate the role of leptin in liver.

PMID- 11448123
TI  - Gene expression of endothelin-1 (ET-1) and release of mature peptide by activated
      human neutrophils.
AB  - Polymorphonuclear neutrophils (PMNs) are only regarded as being involved in the
      cleavage of exogenous big endothelin-1 (ET-1) to the active peptide. The aims of
      the present study were to investigate whether PMNs may themselves express mRNA
      for prepro-ET-1 (pp-ET-1, a long precursor of 212 amino acids) and to determine
      the capacity of several PMN stimulants to modulate mRNA expression and the
      release of ET-1 in culture medium. PMNs, isolated from seven healthy adult
      volunteers, were stimulated with lipopolysaccharide (LPS, 0.25-10 microg/ml), or
      LPS (1 microg/ml) + phorbol myristate acetate (PMA, 10 ng/ml) or N-formyl-L
      methionyl-L-leucyl-L-phenylalanine (f-MLP, 10(-5) M) or tumour necrosis factor
      alpha (TNF-alpha, 50 IU/ml). They were found to express pp-ET-1 mRNA by reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis. Enzyme immunoassay
      (EIA) revealed low levels of ET-1 in the culture supernatants of PMNs stimulated
      for 3 h with LPS (10 microg/ml) and with LPS + PMA. Control unstimulated PMNs did
      not express pp-ET-1 mRNA. The local production of ET-1 by PMNs in vivo has
      significant implications in inflammatory diseases.

PMID- 11448124
TI  - IL-8 and MCP-1 secretion is enhanced by the peptide-nucleic acid immunomodulator,
      Product R, in U937 cells and primary human monocytes.
AB  - Product R (Reticulose) is a peptide-nucleic acid immunomodulator recently shown
      to enhance the expression of mRNAs encoding pro-inflammatory cytokines.
      Interleukin 8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) are pro
      inflammatory chemokines involved in immune cell mobilization and stimulation. To
      determine whether Product R acts by upregulating these chemokines, we assayed its
      effects on the expression of IL-8 and MCP-1 mRNAs and proteins by human monocytic
      U937 cells and by adherent peripheral blood mononuclear cells (PBMCs). U937 cells
      were cultured for 0-21 days in media containing 0-20% Product R or phosphate
      buffered saline (PBS). Compared to control cultures, cells cultured in Product R
      expressed increased amounts of IL-8 and MCP-1 mRNAs, as measured by reverse
      transcriptase-polymerase chain reaction (RT-PCR). Product R also increased
      secretion of IL-8 and MCP-1, as measured by enzyme-linked immunosorbent assay
      (ELISA), and boosted secretion induced by bacterial lipopolysaccharide (LPS), in
      a time- and dose-dependent manner. In adherent PBMCs, Product R increased IL-8
      and MCP-1 secretion, but reduced LPS-induced MCP-1 secretion. While mRNAs
      encoding the IL-8 receptor, CXCR2, and the MCP-1 receptor, CCR2, were increased
      in U937 cells cultured in 5-10% Product R, we observed no change in binding of
      receptor-specific antibodies. These findings suggest that Product R upregulates
      the expression of IL-8 and MCP-1, which may boost immune system activity in
      virally-infected patients.

PMID- 11448125
TI  - Stimulation of TNF-alpha release in monocytes by honey.
AB  - Although evidence exists for the antibacterial effects of honey there is limited
      objective evidence for direct promotion of healing. We investigated the effect of
      manuka, pasture and an artificial honey on macrophage function. Reactive oxygen
      intermediate (ROI) production was assessed by luminol enhanced chemoluminescence
      and tumour necrosis factor-alpha (TNF-alpha) release was determined by
      immunoassay. ROI production was significantly (P<0.001) decreased by pasture
      honey and manuka honey. TNF-alpha release was significantly enhanced (P<0.001) in
      unprimed MM6 cells by manuka and pasture honey but was not altered in primed
      cells. These results could explain the suggested therapeutic properties of honey
      in promoting wound healing.

PMID- 11448126
TI  - Cytokine mRNA expression in mouse colon: IL-15 mRNA is overexpressed and is
      highly sensitive to a fibre-like dietary component (short-chain fructo
      oligosaccharides) in an Apc gene manner.
AB  - On the basis of studies using the Min mouse model of colon carcinogenesis, we
      have recently proposed that a fibre-like food (short-chain fructo
      oligosaccharides, sc-FOS) fermented in the colon may stimulate a mechanism of
      cancer immunosurveillance. In the present paper, we have investigated the
      expression of cytokines as potential effector molecules. Interleukin (IL-)4, IL
      5, IL-13, IL-15 and interferon (INF)-gamma mRNAs were detected by a multi-probe
      ribonuclease protection assay in C57BL/6J and Min mouse colons. IL-15 mRNA
      expression was significantly amplified (P=0.01) by the sc-FOS-enriched diet in
      the colon of Min mice.

PMID- 11448127
TI  - In memorium.

PMID- 11448128
TI  - Essential role of oxygen radicals in delayed pharmacological preconditioning.

PMID- 11448129
TI  - Gq-coupled receptor signaling in pathological ventricular remodeling.

PMID- 11448130
TI  - Functional abrogation of p53 is required for T-Ag induced proliferation in
      cardiomyocytes.
AB  - Targeted expression of the SV40 large T-antigen oncoprotein (T-Ag) induces
      cardiomyocyte proliferation in the atria and ventricles of transgenic mice.
      Previous studies have identified the p53 tumor suppressor, p107 (a homologue of
      the retinoblastoma tumor suppressor), and p193 (a novel BH3 only proapoptosis
      protein) as prominent TAg binding proteins in cardiomyocyte cell lines derived
      from these transgenic mice. To further explore the significance of these protein
      protein interactions in the regulation of cardiomyocyte proliferation, a
      transgene comprising the human atrial natriuretic factor (ANF) promoter and
      sequences encoding a mutant T-Ag lacking the p53 binding domain was generated.
      Repeated micro-injection of this DNA gave rise to genetically mosaic animals with
      minimal transgene content, suggesting that widespread cardiac expression of
      mutant T-Ag was deleterious. This notion was supported by the observation that
      the transgene was selectively lost from the cardiac myocytes (but not the cardiac
      fibroblasts) in the mosaic animals. Crosses between the mosaic mice and animals
      expressing a cardiac restricted dominant negative p53 resulted in transgene
      transmission with ensuing overt cardiac tumorigenesis. Transfection of the mutant
      T-Ag in embryonic stem (ES) cell-derived cardiomyocytes resulted in wide-spread
      cell death with characteristics typical of apoptosis. Co-transfection with a
      dominant negative p53 transgene rescued mutant TAg-induced cell death in the ES
      derived cardiomyocyte cultures, resulting in a marked proliferative response
      similar to that seen in vivo with the rescued transgenic mouse study. These
      results indicate that T-Ag expression in the absence of p53 functional abrogation
      results in cardiomyocyte death.

PMID- 11448131
TI  - NMR spectroscopic characterization of sarcolemmal permeability during myocardial
      ischemia and reperfusion.
AB  - This study aims to characterize the pattern of membrane disintegration during
      myocardial ischemia and reperfusion. Intracellular volumes were measured by 1H
      and 59Co NMR in isolated rat hearts during 10, 30 and 60 min of total ischemia
      and 30 min of reperfusion at normothermia. Perfusion with hypo-osmotic medium
      (210 mosm/l) increased intracellular water from 2.50+/-0.06 to 3.07+/-0.07 ml/g
      dry weight (P<0.001) during pre-ischemia. Hypo-osmotic swelling decreased by 16+/
      3, 32+/-6 and 44+/-11% of the pre-ischemic value after 10, 30 and 60 min of
      ischemia (n.s., P<0.005, P<0.001) respectively, indicating that membrane
      permeabilization facilitated efflux of osmolytes and counterbalanced the osmotic
      driving force for water influx. Hypo-osmotic swelling decreased during 30 min of
      reperfusion by 18+/-5% in all groups (P<0.0.005 v post-ischemia). The volume of
      distribution of the extracellular marker cobalticyanide increased by more than
      3.2+/-0.4 and 5.8+/-0.5% of the intracellular space after 30 and 60 min of
      ischemia respectively (P<0.001), and by an additional 2% after reperfusion.
      During 30 min of reperfusion, hearts released 1.6+/-0.2 and 3.2+/-0.4% of the
      intracellular creatine kinase contents after 30 and 60 min of ischemia,
      respectively (P<0.001). In addition to the correlation between ischemia duration
      and membrane permeability, evident from the analysis of each probe, the data
      showed a progressive increase in severity of membrane injury over time and
      permeabilization to larger molecules. 23Na NMR spectroscopy in conjunction with
      an extracellular shift reagent (SR) showed formation of a resonance at an
      intermediate chemical shift in between the intra and extracellular Na+ peaks,
      suggesting penetration of SR into cells with disrupted membranes. The constant
      chemical shift and narrow line shape of this resonance, characteristic of a
      homogeneous chemical environment, suggested that the distribution of SR was
      contained within the cytosol of cardiomyocytes. We propose that sarcolemmal
      membranes are gradually permeabilized to larger molecules by ischemia, and the
      evolving chemical instability is spatially contained within the myocyte.

PMID- 11448132
TI  - p53 activates the mitochondrial death pathway and apoptosis of ventricular
      myocytes independent of de novo gene transcription.
AB  - The tumor suppressor p53 is known to regulate gene transcription and apoptosis in
      mammalian cells. In the present study we ascertain whether these events are
      mutually dependent and obligatorily linked for induction of apoptosis of
      ventricular myocytes. Adenovirus mediated gene delivery of wild p53 (p53WT) or a
      mutant form of p53 (p53MT) defective for gene transcription to ventricular
      myocytes was confirmed by Western blot analysis. A significant increase in the
      p53 dependent genes Bax and MDM2 was observed with p53WT but not p53MT. Nuclear
      DNA visualized by agarose gel electrophoresis revealed nucleosomal DNA laddering
      in the presence of either p53 protein. Apoptosis was substantiated by Hoechst
      33258 nuclear staining. Perturbations to mitochondria consistent with the
      mitochondrial death pathway, including loss of mitochondrial transmembrane
      potential Delta(psi)m and cytochrome c release were observed with p53WT and
      p53MT. An increase in caspase 3-like activity was noted with either p53WT or
      p53MT protein that was suppressed by the caspase 3 inhibitor Ac-DEVD-CHO. To our
      knowledge the experiments described here provide the first indication that p53
      activates the mitochondrial death pathway and provokes apoptosis of ventricular
      myocytes independent of DNA binding and de novo gene activation.

PMID- 11448133
TI  - Regulation of prostaglandin A1-induced heat shock protein expression in isolated
      cardiomyocytes.
AB  - Prostaglandins of the A-type (PGAs) induce heat shock protein (HSP) synthesis in
      a wide variety of mammalian cells resulting in protection against cellular
      stresses. The effect of PGAs on HSP-induction in cardiac myocytes is unknown.
      Therefore, we investigated the effect of PGA1 on HSP synthesis in adult rat
      cardiac myocytes. After 24 h of treatment, HSP72 was significantly increased 2.9
      , 5.6- and 5.0-fold by PGA1 used at concentrations of 10, 20 or 40 microg/ml,
      respectively (P<0.05). However, the PGA1-concentration of 40 microg/ml, was found
      to be cytotoxic as evidenced by the release of LDH. In addition to HSP72, HSP32
      was significantly increased by PGA1. The HSP32 induction was more vigorous with a
      marked increase with only 4 microg/ml of PGA1. No differences in the levels of
      HSP27, HSP60 or HSP90 were detected. When isolated cardiac myocytes were treated
      with PGA1, clear activation of heat shock factor (HSF) 1, one of the
      transcription factors for HSPs, was observed. In addition, another stress-induced
      transcription factor NFkappaB was also activated by PGA exposure. Despite the
      significant upregulation of both HSP72 and HSP32 cytoprotective properties
      against hypoxia and reoxygenation were absent. In conclusion, these experiments
      show for the first time that PGA1 induces differential expression of heat shock
      proteins in cardiac myocytes probably mediated through the activation of both
      HSF1 and NFkappaB.

PMID- 11448134
TI  - BW373U86, a delta opioid agonist, partially mediates delayed cardioprotection via
      a free radical mechanism that is independent of opioid receptor stimulation.
AB  - Opioids have been shown to produce both an early and delayed phase of
      cardioprotection; however, the signaling pathways involved, particularly in the
      delayed response, have not been well defined. Therefore, we investigated the
      potential of BW373U86 (BW), a potent delta opioid agonist, to produce delayed
      cardioprotection and characterized the role of opioid receptors and oxygen
      derived free radicals (OFRs) in this delayed response. All rats underwent 30 min
      of ischemia followed by 2 h of reperfusion. The rats were divided into four
      groups. First, rats were pretreated with selective opioid receptor antagonists or
      the antioxidant, 2-mercaptopropionyl glycine (2-MPG), in the presence of BW and
      allowed to recover for 24 h before the ischemia-reperfusion protocol. Second,
      rats were pretreated with BW, allowed to recover for 24 h, and subsequently
      treated with either opioid antagonists or 2-MPG, 10 min prior to the ischemia
      reperfusion protocol. Third, rats underwent ischemic preconditioning (IPC) (1x5
      min occlusion) both with and without 2-MPG to determine the role of OFRs in acute
      cardioprotection. Fourth, rats were pretreated with TAN-67, an opioid agonist
      known to signal through the delta1 opioid receptor in the presence and absence of
      2-MPG. Control rats were injected with saline and allowed to recover for 24 h. BW
      produced a bell-shaped dose-related reduction in infarct size with a maximal
      reduction observed at 0.1 mg/kg v control (16+/-3%v 60+/-3%, P<0.001).
      Surprisingly, the delayed protection induced by BW was only partially blocked by
      pretreatment with the delta1-selective antagonist, BNTX; however, it was
      completely blocked by pretreatment with 2-MPG (47+/-5%, P<0.001). Only naloxone
      given acutely inhibited the protective effects of BW; however, at the dose used,
      2-MPG partially reduced the protective effect of acute IPC. TAN-67 (0.1 mg/kg)
      also produced a significant reduction in infarct size compared to control (18+/
      4%v 60+/-3%, P<0.001). This protection was blocked by pretreatment with 2-MPG
      (42+/-4%, P<0.001). These data suggest that BW and TAN-67 mediate delayed
      cardioprotection via a free radical mechanism that appears to be only partially
      dependent on delta opioid receptor stimulation. Furthermore, it is the early
      burst in OFRs that is crucial to initiating the protective effect.

PMID- 11448135
TI  - Expression of cGMP-dependent protein kinase in human atrium.
AB  - We have shown that cGMP-dependent protein kinase (PKG) mediates stimulation of L
      type calcium current by cGMP in rabbit atrial myocytes. The human atrium may have
      similar PKG-dependent regulation of calcium current. To elucidate the
      significance of PKG in cardiac function, we have isolated human PKG type I alpha
      cDNA (+1 to 2016), determined the nucleotide sequence and analyzed specific
      expression of PKG in human atrium. We obtained full-length cDNA of PKG type I
      alpha from human atrial RNA using reverse transcriptase-polymerase chain reaction
      (RT-PCR). The coding region of human cardiac PKG I alpha showed 99.9% homology to
      previously published human PKG I alpha except for base No. 1983. At this position
      G was substituted for T and this resulted in an amino acid substitution from
      Leu649 to Phe649. The cloned PKG I alpha cDNA was expressed in COS cells and the
      expressed PKG showed cGMP-stimulated PKG enzyme activity and immunoreactivity.
      Ribonuclease protection assay, Western blot analysis, and PKG enzyme activity
      assays in homogenates from human atrial tissue demonstrated the presence of PKG
      mRNA and protein in human atrial tissue. Immunofluorescence staining confirmed
      that PKG is highly expressed in human atrial myocytes. These findings suggest
      that PKG is highly expressed in human atrium and that PKG-dependent
      phosphorylation may be important in regulation of calcium channel activity in
      human atrial myocytes.

PMID- 11448136
TI  - Dilated cardiomyopathy in two transgenic mouse lines expressing activated G
      protein alpha(q): lack of correlation between phospholipase C activation and the
      phenotype.
AB  - We previously described a transgenic mouse line (alpha(q)*52) in which cardiac
      specific expression of activated G alpha(q)protein (HA alpha(q)*) leads to
      activation of phospholipase C beta (PLC beta), the immediate downstream target of
      HA alpha(q)*, with subsequent development of cardiac hypertrophy and dilation. We
      now describe a second, independent line in the same genetic background
      (alpha(q)*44h) with lower expression of HA alpha(q)* protein that ultimately
      results in the same phenotype: dilated cardiomyopathy (DCM) with severely
      impaired left ventricular systolic function (assessed by M-mode and 2D
      echocardiography), but with a much delayed disease onset. We asked if PLC
      activation correlates with the development of the phenotype. At 12-14 months, 65%
      of alpha(q)*44h mice still had normal cardiac function and ventricular
      weight/body weight ratios (VW/BW). However, their basal PLC activity, which began
      to increase in ventricles at 6 months, was threefold higher than in wild-type by
      12 months. This increase was even more pronounced than in 2.5-month-old
      alpha(q)*52 mice, in which a twofold increase was accompanied by a 25% increase
      in VW/BW. Furthermore, at 12-14 months the increase in PLC activity in
      alpha(q)*44h mice with and without DCM was comparable. Thus, the delayed time
      course in alpha(q)*44h mice unmasked a lack of correlation between PLC activation
      and development of DCM in response to HA alpha(q)* expression, suggesting a role
      for additional pathways and/or mechanisms. It also revealed a differential
      temporal regulation of protein kinase C isoform expression. The markedly
      different ages of disease onset in these two mouse lines provide a model for
      studying both genetic modifying factors and potential environmental influences in
      DCM.

PMID- 11448137
TI  - Overexpression of cdk Inhibitor p16INK4a by adenovirus vector inhibits cardiac
      hypertrophy in vitro and in vivo: a novel strategy for the gene therapy of
      cardiac hypertrophy.
AB  - Cardiac hypertrophy is one of the serious complications which increase mortality
      due to cardiovascular diseases. However, only a partial reduction of cardiac
      hypertrophy has been successful using current drug therapy. We demonstrate here
      reduction of cardiac hypertrophy in vitro and in vivo using an adenovirus vector
      encoding cyclin-dependent kinase (cdk) inhibitor p16INK4a. Adenovirus-mediated
      overexpression of cdk inhibitor p16INK4a completely inhibited cardiac myocyte
      hypertrophy induced by endothelin (ET)-1, as evaluated by [3H]leucine
      incorporation into the cells and mRNA levels of skeletal alpha -actin (SK-A) or
      atrial natriuretic peptide (ANP) as well as by morphometric analyses. We then
      evaluated whether p16INK4a can suppress left-ventricular (LV) hypertrophy induced
      by aortic banding (AOB) in rats. Catheter-mediated gene transfer of AxCAp16 was
      performed according to the method reported by Hajjar et al. LV overload was
      produced by coarctation of the ascending aorta immediately after inoculation of
      the heart with adenovirus. Two weeks after the procedure, the left ventricular
      weight/body weight ratio (LVW/BW) increased in the AOB+LacZ group in comparison
      to that in controls. However, LVW/BW was identical in the AOB+p16 group and
      controls. Histologic analysis revealed that p16INK4a inhibited hypertrophy of
      cardiac myocytes. These results suggest that G1 cell cycle regulators may
      restrict cardiac hypertrophy, and offer a novel strategy for the gene therapy of
      cardiac hypertrophy.

PMID- 11448138
TI  - Cyclosporine reduces left ventricular mass with chronic aortic banding in mice,
      which could be due to apoptosis and fibrosis.
AB  - A tacit assumption in studies of left ventricular (LV) hypertrophy is that left
      ventricular/body weight (LV/BW) reflects the extent of myocyte hypertrophy. The
      goal of the current investigation was to determine if there was another
      explanation for the reduced LV/BW observed after inhibiting calcineurin with
      cyclosporine during the development of pressure overload LV hypertrophy as
      compared with animals that did not receive cyclosporine. Accordingly, we examined
      the prevalence of fibrosis and apoptosis and measured cell size in the hearts
      from mice at 1 and 3 weeks after transverse aortic banding with and without
      chronic cyclosporine. Although LV/BW, compared to aortic banded vehicle treated
      mice, was reduced by 30% in aortic banded cyclosporine treated mice, myocyte
      cross sectional area was similar in both banded groups (346+/-9 microm2 v 336+/
      13 microm2). The volume percent interstitial fibrosis was greater in aortic
      banded cyclosporine treated animals (1.4+/-0.2%) compared with aortic banded
      vehicle treated animals (0.9+/-0.2%, P<0.05) or in sham animals (0.6+/-0.1%).
      Surprisingly, lesions including myocytes containing iron were observed and were
      most prominent in aortic banded cyclosporine treated animals. Apoptosis,
      quantitated with TUNEL staining as percent of myocytes, was increased in aortic
      banded cyclosporine treated animals at 7 days (1.6+/-0.4%) compared with aortic
      banded vehicle treated animals (0.4+/-0.1%, P<0.01) and was still increased at 21
      days. Immunoblotting demonstrated a decrease in the phosphorylation of Akt and
      Bad, and also Bcl-2 levels were reduced in aortic banded cyclosporine treated
      animals at 7 days compared with aortic banded vehicle treated animals. These
      proteins protect against apoptosis, and support the concept that cyclosporine
      inhibited the calcineurin pathway, resulting in enhanced apoptosis. Thus, the
      decrease in LV/BW in the aortic banded cyclosporine treated animals actually may
      be due, at least in part, to cell loss and death, as reflected by the enhanced
      fibrosis and apoptosis and the focal iron deposits in myocytes.

PMID- 11448139
TI  - Autoantibodies against the beta1 adrenoceptor from patients with dilated
      cardiomyopathy prolong action potential duration and enhance contractility in
      isolated cardiomyocytes.
AB  - Autoantibodies against the beta1-adrenoceptor (beta1-AAB) from patients with
      dilated cardiomyopathy (DCM) increase the beating frequency of cultured neonatal
      rat cardiomyocytes. This effect is accompanied by only a small increase in cAMP
      production. Here we have investigated whether beta1-AAB affect
      electrophysiological properties and cell shortening of isolated cardiomyocytes by
      interacting with the beta1-adrenoceptor. Beta1-AAB were obtained during
      immunoadsorption of patients with DCM and were used for experiments in isolated
      myocytes cultured from neonatal rat hearts, or freshly isolated from adult rat
      ventricles or from human right atria. The unselective beta -adrenoceptor agonist
      (-)-isoprenaline was studied for comparison. Immunoglobulin G (IgG) antibodies
      increased the spontaneous beating frequency of neonatal rat cardiomyocytes to a
      lesser degree than (-)-isoprenaline, but both effects were maximum and stable
      after 2 min. In rat ventricular and human atrial myocytes, IgG increased action
      potential duration (APD) in a concentration-dependent manner with larger effects
      on late than on early repolarization phases. Similar effects were obtained with
      purified beta1-AAB, whereas flow through of the chromatography column was
      ineffective. (-)-isoprenaline prolonged APD to the same extent during plateau and
      late phase of repolarization. beta1-AAB increased L-Type Ca2+ current in
      correspondence with the prolongation of APD. The effects of beta1-AAB and (-)
      isoprenaline on APD were strongly attenuated after preincubation of the myocytes
      with the selective beta1-adrenoceptor antagonist (-)-bisoprolol. In addition,
      beta1-AAB increased cell shortening in ventricular myocytes from adult rat
      hearts. Beta1-AAB enhancing the beating frequency of cultured cardiomyocytes,
      increase L-Type Ca2+ current, APD and contractility in freshly isolated
      cardiomyocytes mediated via beta1-adrenoceptors. These effects may contribute to
      beta1-adrenoceptor-mediated cardiotoxicity in heart failure.

PMID- 11448140
TI  - Decreased p38 MAPK activity in end-stage failing human myocardium: p38 MAPK alpha
      is the predominant isoform expressed in human heart.
AB  - Short duration exposure to cellular stresses have been shown to activate p38
      mitogen-activated protein kinase (MAPK) in cultured rat ventricular
      cardiomyocytes and isolated perfused hearts; however, effects of chronic stress
      on p38 MAPK are not well understood. This study determined whether alterations in
      the p38 MAPK pathway occurred prior to end-stage human heart failure. The p38
      MAPK alpha isoform was detectable in human cardiac tissue. However, carefully
      controlled analysis of protein and message in this study demonstrated an absence
      of the p38 MAPK beta -isoform. Low levels of message for the non-SB203580
      sensitive p38 MAPK gamma and delta isoforms were also detected in both normal and
      failing human myocardium. Ischemic and idiopathic end-stage failing human hearts
      were compared to non-failing hearts for both p38 alpha MAPK protein level and
      total p38 MAPK activity. Western blotting techniques demonstrated no significant
      changes in total p38 alpha MAPK content. However, approximately 75% decreases in
      active/phosphorylated p38 MAPK (P<0.005) were observed in both ischemic and
      idiopathic failing hearts compared to non-failing hearts. In-gel kinase assays
      confirmed that activated p38 MAPK, detected by Western blotting, phosphorylated
      its potential downstream targets. When compared to non-failing hearts,
      approximately 46% decreases in p38 MAPK phosphorylation of mitogen-activated
      protein kinase-activated protein kinase-2 (MAPKAPK-2) were observed in ischemic
      and idiopathic failing hearts (P=0.03 and P=0.04 respectively). Active p38 MAPK
      was localized to sarcomeric structures in the cytosol of myocytes by confocal
      immunofluorescence microscopy. The correlation between decreased MAPKAPK-2
      phosphorylation and loss of active p38 MAPK in failing human myocytes suggests
      that decreases in the activation of p38 MAPK alpha, the predominant cardiac
      isoform, occur prior to end-stage heart failure.

PMID- 11448141
TI  - Is the molecular composition of K(ATP) channels more complex than originally
      thought?
AB  - ATP-sensitive K+ (K(ATP)) channels are abundantly expressed in the heart and may
      be involved in the pathogenesis of myocardial ischemia. These channels are
      heteromultimeric, consisting of four pore-forming subunits (Kir6.1, Kir6.2) and
      four sulfonylurea receptor (SUR) subunits in an octameric assembly.
      Conventionally, the molecular composition of K(ATP) channels in cardiomyocytes
      and pancreatic beta -cells is thought to include the Kir6.2 subunit and either
      the SUR2A or SUR1 subunits, respectively. However, Kir6.1 mRNA is abundantly
      expressed in the heart, suggesting that Kir6.1 and Kir6.2 subunits may co
      assemble to form functional heteromeric channel complexes. Here we provide two
      independent lines of evidence that heteromultimerization between Kir6.1 and
      Kir6.2 subunits is possible in the presence of SUR2A. We generated dominant
      negative Kir6 subunits by mutating the GFG residues in the channel pore to a
      series of alanine residues. The Kir6.1-AAA pore mutant subunit suppressed both wt
      Kir6.1/SUR2A and wt-Kir6.2/SUR2A currents in transfected HEK293 cells. Similarly,
      the dominant negative action of Kir6.2-AAA does not discriminate between either
      of the wild-type subunits, suggesting an interaction between Kir6.1 and Kir6.2
      subunits within the same channel complex. Biochemical data support this concept:
      immunoprecipitation with Kir6.1 antibodies also co-precipitates Kir6.2 subunits
      and conversely, immunoprecipitation with Kir6.2 antibodies co-precipitates Kir6.1
      subunits. Collectively, our data provide direct electrophysiological and
      biochemical evidence for heteromultimeric assembly between Kir6.1 and Kir6.2.
      This paradigm has profound implications for understanding the properties of
      native K(ATP)channels in the heart and other tissues.

PMID- 11448143
TI  - Leukaemia inhibitory factor (LIF): a cytokine of emerging importance in chronic
      airway inflammation.
AB  - Inflammation is a complex set of mechanisms by which tissues respond to an
      injury. These responses involve the coordinated interaction between the nervous
      and immune systems. An integral part of this interaction is the release of a
      variety of cytokines that regulate cellular and molecular responses. Leukaemia
      Inhibitory Factor (LIF), a member of the IL-6 family of cytokines, has been shown
      to be an integral component of the interface between nerves and the immune
      system. However, little is known about this cytokine in the context of normal
      lung function or indeed, inflammation. Evidence is emerging that this cytokine
      may play an important role in regulating the neural-immune system interaction
      during acute inflammatory insult and the subsequent healing and restitution
      process. However, LIF may act as either a pro- or antiinflammatory cytokine,
      depending on the cell type and a number of other variables. In this review, the
      role of LIF in airway inflammation and resolution of inflammation is discussed.
      In particular, recent work suggesting that LIF is a mediator of bi-directional
      cross-talk between neural tissue and the immune system is highlighted.

PMID- 11448144
TI  - The impact of inflammation on bronchial neuronal networks.
AB  - It is well-recognized that the activities of airway neuronal systems can be
      modulated by various agonist molecules. This brief review examines some of the
      evidence that inflammation and some of the mediators relevant to the expression
      of inflammatory processes can also significantly alter the function and
      activities of airway nerves. The concept of neuronal plasticity and phenotype
      switching induced by inflammation is also examined, with particular emphasis on
      sensory airway nerves.

PMID- 11448145
TI  - Protease-activated receptor-2 (PAR2) in the airways.
AB  - Protease-activated receptors (PARs) act as sensors for active extracellular
      serine proteases. Since serine proteases like mast cell tryptase are associated
      with inflammatory processes, PARs may represent novel pharmacological targets in
      airway diseases like asthma and chronic obstructive pulmonary disease. However,
      our present understanding of the physiological roles of PARs is in its infancy.
      In this review we highlight evidence for the involvement of PARs in airway
      disease and propose that these novel receptors may play mainly protective roles.

PMID- 11448146
TI  - Chemokine receptors in airway disease: which receptors to target?
AB  - Many disease states within the airway result in the co-ordinated infiltration of
      key inflammatory cells. The cellular influx is choreographed through the temporal
      and spatially-regulated expression of chemokines, which potentiate the migration
      of cells along gradients of chemotactic ligands. Chemokines act as ligands for
      the chemokine receptors; a distinct class of G-protein-coupled receptor. Over 40
      chemokine ligands and 18 chemokine receptors have been identified on human cells.
      Chemokine receptors are divided into several classes; the two most prominent of
      which are the CC- and CXC-chemokine receptors, classified through the spatial
      arrangement of two conserved cysteine residues. The role of chemokine receptors
      such as CCR2, CCR3, CCR4, CCR8 and the CXC chemokine receptors; CXCR1 and CXCR2
      on cell types of relevance to respiratory diseases such as asthma, chronic
      obstructive pulmonary disease (COPD) and chronic bronchitis will be explored in
      this review. Chemokines have proven to be amenable drug targets for the
      development of low molecular weight antagonists by the pharmaceutical industry.
      So far, no chemokine receptor antagonist has entered the clinic in trials for
      respiratory disease, but over the next few years it is expected that many will do
      so, at which time the potential of these exciting new targets will be fully
      realised.

PMID- 11448147
TI  - Important roles for L-selectin and ICAM-1 in the development of allergic airway
      inflammation in asthma.
AB  - Airway inflammation and airway hyperresponsiveness (AHR) are fundamental features
      of asthma. Migration of inflammatory cells from the circulation into the lungs is
      dependent upon adhesion molecule interactions. The cell surface adhesion
      molecules L-selectin and intercellular adhesion molecule (ICAM)-1 have been
      demonstrated to mediate leukocyte rolling on inflamed pulmonary endothelium, and
      ICAM-1 has also been shown to mediate capillary sequestration in inflamed lung.
      However, their roles in the development of airway inflammation and AHR in asthma
      have not been directly examined. We have characterised the roles of L-selectin
      and ICAM-1 in the recruitment of inflammatory cells to the lung and in the
      development of airway hyperresponsiveness using an ovalbumin (OVA)-induced
      allergic airway disease model of asthma and adhesion molecule-deficient mice. OVA
      sensitized/challenged ICAM-1-deficient mice have dramatically reduced
      inflammatory influx into the airway/lung and a corresponding attenuation of AHR
      as compared to wild-type controls. OVA-sensitized/challenged L-selectin-deficient
      mice demonstrate significantly reduced numbers of CD3(+)lymphocytes and increased
      numbers of B220(+)lymphocytes in BAL as compared to wild-type mice (P< 0.05).
      However, other parameters of airway/lung inflammation in OVA
      sensitized/challenged L-selectin-deficient mice were equivalent to wild-type
      control mice. Remarkably, despite a fulminant inflammatory response in the
      airway/lung, AHR was completely abrogated in OVA-sensitized/challenged L-selectin
      deficient mice. These findings suggest a crucial role for ICAM-1 in the
      development of airway inflammation and AHR in asthma. In contrast, L-selectin
      plays a more selective role in the development of airway hyperresponsiveness but
      not allergic inflammation in this animal model of asthma. Thus, L-selectin and
      ICAM-1 represent potential targets for novel asthma therapies specifically aimed
      at controlling airway inflammation and/or airway hyperresponsiveness.

PMID- 11448148
TI  - Glucocorticoid-regulated transcription factors.
AB  - Glucocorticoids are the most effective antiinflammatory drugs used in the
      treatment of asthma. They act by binding to a specific receptor (GR) that, upon
      activation, translocates to the nucleus and either increases (transactivates) or
      decreases (transrepresses) gene expression. Inhibition of pro-inflammatory
      transcription factors such as activator protein (AP)-1, signal transducers and
      activators of transcription (STATs), nuclear factor of activated T cells (NFAT)
      and nuclear factor (NF)-kappa B is thought to be a major action of
      glucocorticoids. Acetylation of histones allows unwinding of the local DNA
      structure and enables RNA polymerase II to enhance gene transcription. Histone
      acetylation is regulated by a balance between the activity of histone
      acetyltransferases (HATs) and histone deacetylases (HDACs). GR acts as a direct
      inhibitor of NF-kappa B-induced HAT activity and also by recruiting HDAC2 to the
      NF-kappa B/HAT complex. A sub-group of patients with glucocorticoid-insensitive
      asthma have an inability to induce histone acetylation in response to
      dexamethasone suggesting reduced expression of a GR-specific HAT. This suggests
      that pharmacological manipulation of specific histone acetylation status is a
      potentially useful approach for the treatment of inflammatory diseases.
      Identification of the precise mechanism by which activated GR recruits HDAC2 may
      reveal new targets for the development of drugs that may dissociate the
      antiinflammatory actions of glucocorticoids from their side effects that are
      largely due to gene induction.

PMID- 11448149
TI  - New Glucocorticosteroids with an improved therapeutic ratio?
AB  - Glucocorticoids (GCs) remain the most effective therapy for inflammatory
      disorders. In terms of asthma, topical steroids are the mainstay for controlling
      the inflammatory component of the disease. However, their use is limited by the
      constellation of adverse effects associated with chronic, oral steroid use and
      the long-term adverse effects associated with inhaled steroid use. These include
      suppression of hypothalamic--pituitary axis, osteoporosis, reduced bone growth in
      the young, opportunistic infections, behavioural alterations, and disorders of
      lipid metabolism. Most of these effects may be attributable to the endocrine
      activity of steroids and are largely identical to the syndromes of endogenous
      corticosteroid excess (Cushing's Syndrome). Thus, the Holy Grail of steroid
      pharmacology is the development of agents which have a markedly improved
      therapeutic ratio than current steroids, especially on systemic administration.
      This may be achieved by the identification of molecules which elicit marked
      antiinflammatory effects, but have a minor impact on endocrine responses.
      Dissociated corticosteroids are ligands for the glucocorticoid receptor that may
      offer the potential for a more selective antiinflammatory profile.

PMID- 11448150
TI  - Assessing the evidence for remodelling of the airway in asthma.
AB  - Asthma is now described as being characterized by reversible airflow obstruction,
      with bronchial inflammation and tissue remodelling of the airway wall. The
      description of remodelling has been usefully invoked to account for a component
      of airflow obstruction that is unresponsive to usual bronchodilator therapy. It
      is crucial to examine critically the evidence for this view, particularly the
      quantitation of specific changes in the epithelium, mucus glands, cell
      infiltrate, collagen, vessels and smooth muscle of the bronchial wall. The useful
      tools of immunohistochemistry and molecular biology combined with airway biopsy
      and well-designed clinical trials will be essential to determine the specific
      roles of cells and cytokines in airway remodelling in asthma.

PMID- 11448151
TI  - Glycosaminoglycans, airways inflammation and bronchial hyperresponsiveness.
AB  - Glycosaminoglycans (GAGs) are large, polyanionic molecules expressed throughout
      the body. The GAG heparin, co-released with histamine, is synthesised by and
      stored exclusively in mast cells, whereas the closely related molecule heparan
      sulphate is expressed, as part of a proteoglycan, on cell surfaces and throughout
      tissue matrices. These molecules are increasingly thought to play a role in
      regulation of the inflammatory response and heparin, for many years, has been
      considered to hold potential in the treatment of diseases such as asthma. Heparin
      and related molecules have been found to exert antiinflammatory effects in a wide
      range of in vitro assays, animal models and, indeed, human patients. Moreover,
      the results of studies carried out to date indicate that the antiinflammatory
      activities of heparin are dissociable from its well-established anticoagulant
      nature, suggesting that the separation of these characteristics could yield novel
      antiinflammatory drugs which may be useful in the future treatment of diseases
      such as asthma

PMID- 11448152
TI  - Airway wall remodelling and hyperresponsiveness: modelling remodelling in vitro
      and in vivo.
AB  - Airway wall remodelling contributes to the airway hyperresponsiveness that
      characterizes asthma. An increase in airway smooth muscle (ASM) volume is
      quantitatively important in the overall remodelling response and may be
      considered as a target for new therapeutic approaches to chronic asthma. ASM
      volume increases result from both hypertrophic as well as hyperplastic growth,
      the latter having been more extensively investigated. There are relatively few in
      vivo models available for analysis of the underlying mechanism(s) or their
      regulation by drugs. Human ASM in culture has been used to investigate potential
      stimuli for ASM proliferation and the signal transduction pathways that subserve
      these responses. The mitogen-activated protein kinase (MAPK) family members, ERK
      1/2 and the phosphoinositol-3-kinase (PI3K) pathways each contribute to the
      signalling of G1 progression/S-phase entry in ASM. Glucocorticoids and beta(2)
      adrenoceptor agonists attenuate, but do not prevent proliferative responses of
      ASM. Thus, there is scope for improved pharmacological control of this chronic
      and progressive aspect of asthma pathogenesis.

PMID- 11448153
TI  - The role of DC-SIGN and DC-SIGNR in HIV and SIV attachment, infection, and
      transmission.

PMID- 11448154
TI  - The white spot syndrome virus DNA genome sequence.
AB  - White spot syndrome virus (WSSV) is at present a major scourge to worldwide
      shrimp cultivation. We have determined the entire sequence of the double
      stranded, circular DNA genome of WSSV, which contains 292,967 nucleotides
      encompassing 184 major open reading frames (ORFs). Only 6% of the WSSV ORFs have
      putative homologues in databases, mainly representing genes encoding enzymes for
      nucleotide metabolism, DNA replication, and protein modification. The remaining
      ORFs are mostly unassigned, except for five, which encode structural virion
      proteins. Unique features of WSSV are the presence of a very long ORF of 18,234
      nucleotides, with unknown function, a collagen-like ORF, and nine regions,
      dispersed along the genome, each containing a variable number of 250-bp tandem
      repeats. The collective information on WSSV and the phylogenetic analysis on the
      viral DNA polymerase suggest that WSSV differs profoundly from all presently
      known viruses and that it is a representative of a new virus family.

PMID- 11448155
TI  - Activated Notch1 signaling cooperates with papillomavirus oncogenes in
      transformation and generates resistance to apoptosis on matrix withdrawal through
      PKB/Akt.
AB  - Invasive cervical tumors, a major subset of human epithelial neoplasms, are
      characterized by the consistent presence of papillomavirus oncogenes 16 or 18 E6
      and E7 products. Cervical tumors also consistently exhibit cytosolic and nuclear
      forms of Notch1, suggesting the possible persistent activation of the Notch
      pathway. Here we show that activated Notch1 synergizes with papillomavirus
      oncogenes in transformation of immortalized epithelial cells and leads to the
      generation of resistance to anoikis, an apoptotic response induced on matrix
      withdrawal. This resistance to anoikis by activated Notch1 is mediated through
      the activation of PKB/Akt, a key effector of activated Ras in transformation. We
      suggest that activated Notch signaling may serve to substitute for the lack of
      activated Ras mutations in the majority of human cervical neoplasms.

PMID- 11448156
TI  - Analysis of cellular factors influencing the replication of human
      immunodeficiency virus type I in human macrophages derived from blood of
      different healthy donors.
AB  - We analyzed parameters influencing HIV-1 infectibility of cells of the
      monocyte/macrophage lineage (MO/MAC) isolated from different healthy donors. The
      proportion of in vitro-infected cells and replication kinetics in different donor
      MAC ranged from 0.03 to 99% p24 antigen-positive MAC and from undetectable RT
      activity up to 5 x 10(6) cpm/ml/90 min, respectively. As a quantitative
      measurement for HIV-1 susceptibility of donor MO/MAC, we determined TCID(50)
      values of defined virus stocks which varied up to 3000-fold depending on the
      donor MAC used for titration. As host factors which may influence the viral
      infection we determined the expression of virus receptors CD4, CCR5, CXCR4, and
      CCR3 as well as the secretion of the natural ligands of CCR5, which altogether
      showed no correlation with HIV-1 infectibility of the cells. Moreover, other MO
      derived secretory factors which might affect viral infection of these cells could
      be excluded. Furthermore, expression of maturation-related antigens CD14, CD16,
      HLA-DR, and MAX.1/CPM was determined. Analysis of the reverse transcription
      process revealed that restricted HIV-1 infection was reflected by highly reduced
      or even undetectable full-length HIV-1 DNA formation, although early and
      intermediate transcripts appeared, suggesting that viral replication is blocked
      after entry at the level of early reverse transcription.

PMID- 11448157
TI  - Analysis of dominant-negative effects of mutant Env proteins of human
      immunodeficiency virus type 1.
AB  - The Env protein of human immunodeficiency virus type 1 is assembled into a stable
      trimer, and oligomerization is required for maintenance of viral infectivity.
      This property of Env suggests that Env mutants may have a dominant-negative
      effect on virus infectivity. To investigate this possibility, we established a
      packaging cell line in which both wild-type and mutant Env proteins could be
      expressed simultaneously in a single cell. We analyzed the effects of two types
      of Env mutants: cytoplasmic tail-truncated TM mutants and a mutant defective in
      gp120/gp41 cleavage. The cytoplasmic tail-truncated proteins were found to be
      incorporated into virions by forming an oligomer with wild-type TM, but could not
      inhibit the wild-type function. In contrast, phenotypic mixing of cleavage
      defective Env with the wild-type protein caused dramatic inhibition of
      infectivity, indicating that this mutant has a strong dominant-negative
      phenotype.

PMID- 11448158
TI  - Amino acid substitution(s) in the stem-anchor region of langat virus envelope
      protein attenuates mouse neurovirulence.
AB  - The identification of variants that are unable to bind membrane receptor
      preparations (MRPs) has previously been shown to select attenuated yellow fever
      and Japanese encephalitis viruses. In this study, this methodology has been
      extended to the tick-borne serocomplex of flaviviruses. Langat (LGT) virus strain
      TP21 was bound to mouse or human brain MRPs and viruses that escaped binding were
      isolated and characterized. In addition, variant viruses escaping neutralization
      by the monoclonal antibody (MAb) 9F9 were also isolated. All of the variant
      viruses were attenuated for mouse neurovirulence (> or =13-fold). Sequence
      analysis of the prM/E region of the variant viruses identified mutations within
      the stem-anchor region of the E protein in variants isolated following incubation
      with mouse or human brain MRPs at a pH > or = 7.0. The MAb 9F9 variants and MRP
      variants isolated at pH 5.0, which should induce a conformational shift in the
      viral E protein, had nearly identical mutations in the prM/M protein immediately
      N-terminal to the prM/E cleavage site. MAb 9F9 neutralized none of the variant
      viruses and hemagglutination inhibition assays suggest that the variant virus
      surface proteins have slightly different conformations compared to the parental
      virus. These data support previous work indicating that the stem-anchor region of
      the E protein is important to the surface architecture of the tick-borne
      flaviviruses. In addition, this study demonstrates that the M protein is at least
      partially solvent accessible on the virion surface and that the M protein plays a
      role in maintaining the conformation of the M/E surface complex.

PMID- 11448159
TI  - HIV Tat activates c-Jun amino-terminal kinase through an oxidant-dependent
      mechanism.
AB  - The HIV-1 accessory protein Tat has been found to exert profound effects on
      vascular cell behavior. Recently, Tat has been found to activate the c-Jun amino
      terminal kinase (JNK1, SAPK) MAP kinase in lymphoid cells. We found that purified
      Tat rapidly activated JNK1 in human umbilical vein endothelial cells and ECV-304
      cells, and coculture of ECV-304 cells with Tat-transfected HeLa cells resulted in
      persistent activation of JNK1. In addition, lower doses of Tat potentiated
      TNFalpha-induced JNK1 activation, although higher doses paradoxically diminished
      JNK1 activation by TNFalpha. Treatment of ECV-304 cells with Tat acutely
      increased intracellular oxidant levels, and Tat-induced oxidant activity was
      decreased by two structurally distinct NADPH oxidase inhibitors, diphenylene
      iodonium and apocynin. Both oxidase inhibitors and the thiol antioxidant N-acetyl
      cysteine decreased Tat-induced JNK1 activation in parallel with reduction in
      oxidant levels. Activation of JNK1 by Tat was also inhibited by cytochalasin B,
      suggesting that Tat signaling was dependent upon intact cytoskeletal function.
      Indeed, JNK1 activation by Tat was associated with actin microfilament
      rearrangement. We conclude that HIV Tat may cause acute and persistent activation
      of the JNK MAP kinase through activation of a specific oxidase.

PMID- 11448160
TI  - Analysis of a three-dimensional structure of Potato leafroll virus coat protein
      obtained by homology modeling.
AB  - Viruses of the family Luteoviridae are ssRNA plant viruses that have particles
      that exhibit icosahedral symmetry. To identify the residues that might be exposed
      on the surface of the Potato leafroll virus (PLRV; genus Polerovirus, family
      Luteoviridae) capsid, and therefore involved in biological interactions, we
      performed a structural analysis of the PLRV coat protein (CP) on the basis of
      comparisons with protein sequences and known crystal structures of CPs of other
      viruses. The CP of PLRV displays 33% sequence similarity with that of Rice yellow
      mottle virus (genus Sobemovirus) when the sequences were aligned by using the
      hidden Markov model method. A structure model for PLRV CP was designed by protein
      homology modeling, using the crystal structure of RYMV as a template. The
      resulting model is consistent with immunological and site-directed mutagenesis
      data previously reported. On the basis of this model it is possible to predict
      some surface properties of the PLRV CP and also speculate about the structural
      evolution of small icosahedral viruses.

PMID- 11448161
TI  - The porcine endogenous retrovirus long terminal repeat contains a single
      nucleotide polymorphism that confers distinct differences in estrogen receptor
      binding affinity between PERV A and PERV B/C subtypes.
AB  - Porcine endogenous retroviruses (PERV) have been shown to have zoonotic
      potential, both in vitro and in vivo. Once integrated into the host cell genome
      activation of the proviral genes is ultimately dependent upon transactivation of
      the long terminal repeat (LTR). Currently there is no direct evidence of host
      cell transcription factors interacting with PERV LTRs. Using comparative genomics
      we discovered a potentially functional single nucleotide polymorphism (SNP)
      within the U5 region downstream of the TATA box in the PERV LTR that
      distinguishes PERV A from PERV B and PERV C subtypes. We demonstrated that the
      SNP occurs within a potential hormone-responsive region where it has a profound
      effect, not only upon estrogen receptor binding but also upon the binding of
      other transcription factors at this site. These results suggest that differences
      in transcriptional regulation between PERV subtypes are subtle and, as for other
      retroviruses, transcription can be mediated by steroid hormone receptors.

PMID- 11448162
TI  - 12-O-tetradecanoylphorbol-13-acetate induces Epstein-Barr virus reactivation via
      NF-kappaB and AP-1 as regulated by protein kinase C and mitogen-activated protein
      kinase.
AB  - Signaling pathway components mediating Epstein-Barr virus (EBV) reactivation by
      12-O-tetradecanoylphorbol-13-acetate (TPA) were characterized in terms of
      induction and modification of specific transacting factors. The consequences of
      protein kinase C (PKC) activation by TPA in inhibiting inducible nitric oxide
      synthase (iNOS) mRNA expression were analyzed in the EBV-infected gastric
      epithelial cell line GT38. Spontaneous expression of the EBV BZLF1 gene product
      ZEBRA became undetectable upon long-term culturing of GT38 cells, while iNOS mRNA
      expression increased. In such cells the PKC inhibitors 1-(5
      isoquinolinesulphonyl)-2,5-dimethylpiperazine (H7) and staurosporine inhibited
      TPA-induced expression of BZLF1 and BRLF1 and reversed TPA-mediated inhibition of
      iNOS gene expression. The mitogen-activated protein kinase inhibitor PD98059
      inhibited TPA-induced BZLF1 expression. Electrophoretic mobility shift assays
      demonstrated that transcription factors NF-kappaB and AP-1 were also activated by
      TPA in a time-dependent manner. The TPA-induced NF-kappaB activation was
      inhibited by prior treatment of the cells with the NF-kappaB inhibitor
      pyrrolidine dithiocarbamate (PDTC). TPA-induced BZLF1 expression was also
      inhibited by the treatment with PDTC. Northern blot analyses characterized
      changes in levels of the c-jun and junB expressions of the AP-1 family. These
      results show that TPA induces EBV reactivation via NF-kappaB and AP-1 and that
      PKC is an important mediator in regulating gene expression leading to EBV
      reactivation after TPA treatment of GT38 cells.

PMID- 11448163
TI  - Broad distribution of the JC virus receptor contrasts with a marked cellular
      restriction of virus replication.
AB  - To investigate the early events of JC virus (JCV) infection, including
      attachment, penetration, transport to the nuclei, and replication of the virus,
      we analyzed the susceptibility of 15 different cell lines to infection using a
      semiquantitative polymerase chain reaction (PCR) assay, in situ hybridization,
      laser scanning confocal microscopy, and a viral replication assay. The cell lines
      examined were human permissive and nonpermissive cells as well as cells of monkey
      and mouse origin. JCV entry into the nuclei of the all cell lines was observed
      within 10 min after inoculation, demonstrating that the virus receptor is widely
      distributed among mammalian cells. Inhibition of viral entry by an anti-JCV VP1
      antibody and sialidase treatment to remove sialic acid residues, which are
      considered a candidate for the JCV receptor, suggested that VP1 may interact with
      the cellular surface sialic acid. In addition, chlorpromazine, a clathrin
      dependent pathway inhibitor, significantly suppressed entry of JCV into nuclei.
      In spite of the broad spectrum of cells susceptible to JCV entry, replication of
      the virus occurred exclusively in human neuroblastoma cell lines. These results
      suggest that whereas JCV can enter a wide variety of cell types and localize to
      the nuclei, cell-specific intranuclear mechanisms are required for virus
      replication.

PMID- 11448164
TI  - Reverse genetics and recombination in Phi8, a dsRNA bacteriophage.
AB  - Bacteriophage Phi8 has a genome of three dsRNA segments. It is able to acquire
      plasmid transcripts of cDNA copies of the genomic segments as replacements of its
      resident chromosomes. It is also able to effect recombination between the plasmid
      transcripts and the resident chromosomes. Depending upon the extent of sequence
      identity between the plasmid transcript and the resident chromosome, the
      recombination can be homologous or heterologous. Homologous recombination has not
      previously been reported for viruses with double-stranded RNA genomes.

PMID- 11448165
TI  - Herpes simplex virus type 1 suppresses the interferon signaling pathway by
      inhibiting phosphorylation of STATs and janus kinases during an early infection
      stage.
AB  - We examined the influence on the interferon (IFN) signaling pathway of infection
      with herpes simplex virus type 1 (HSV-1) strain VR3. Data from reporter gene
      assays showed that expression of both type I and type II IFN-inducible genes was
      dramatically suppressed during the early stage of HSV-1 infection (2 to 3 h
      postinfection). During these periods, phosphorylation levels of janus kinases
      (JAKs) and STATs did not increase after treatment of HSV-1-infected FL cells with
      IFN-alpha or IFN-gamma, although cellular protein levels of the JAKs and the
      STATs were not significantly changed. In contrast, the inhibitory effect of HSV-1
      on phosphorylation of STAT1 was not observed in U937 cells, which show resistance
      to steady-state accumulation of RNA for HSV-1 immediate-early genes. The
      phosphorylation of STAT1 in FL cells was not inhibited by infection with a UV
      inactivated virus. These results indicate that viral gene expression or viral
      protein production is necessary for the inhibition of phosphorylation by HSV-1.

PMID- 11448166
TI  - Vector specificity of barley yellow dwarf virus (BYDV) transmission:
      identification of potential cellular receptors binding BYDV-MAV in the aphid,
      Sitobion avenae.
AB  - Two proteins (SaM35 and SaM50) isolated from head tissues of the aphid vector,
      Sitobion avenae, were identified as potential receptors for barley yellow dwarf
      virus MAV isolate (Luteoviridae) based on MAV virus overlay assays and
      immunoblots of urea SDS 2-D gels. An anti-idiotypic antibody (MAV4 anti-ID) that
      mimics an epitope on MAV virions and competes with MAV in antibody binding assays
      also bound to SaM50 and SaM35 and to six additional proteins including a GroEL
      homolog. No MAV-binding proteins were detected from the nonvector aphid,
      Rhopalosiphum maidis, although MAV4 anti-ID did react with four proteins from R.
      maidis. It is hypothesized that SaM35 and SaM50 may be MAV receptors involved in
      MAV transmission based on their high affinity for MAV and their unique
      association with the vector, S. avenae. The additional aphid proteins binding the
      MAV4 anti-ID may represent less specific virus-binding proteins facilitating
      transmission through different aphid tissues.

PMID- 11448167
TI  - Characterization of the cis-acting elements controlling subgenomic mRNAs of
      citrus tristeza virus: production of positive- and negative-stranded 3'-terminal
      and positive-stranded 5'-terminal RNAs.
AB  - Citrus tristeza virus (CTV), a member of the Closteroviridae, has an
      approximately 20-kb positive-sense RNA genome with two 5' ORFs translated from
      the genomic RNA and 10 3' genes expressed via nine or ten 3'-terminal subgenomic
      (sg) RNAs. The expression of the 3' genes appears to have properties intermediate
      between the smaller viruses of the "alphavirus supergroup" and the larger viruses
      of the Coronaviridae. The sgRNAs are contiguous with the genome, without a common
      5' leader, and are associated with large amounts of complementary sgRNAs.
      Production of the different sgRNAs is regulated temporally and quantitatively,
      with the highly expressed genes having noncoding regions (NCR) 5' of the ORFs.
      The cis-acting elements that control the highly expressed major coat protein (CP)
      gene and the intermediately expressed minor coat protein (CPm) gene were mapped
      and compared. Mutational analysis showed that the CP sgRNA controller element
      mapped within nts -47 to -5 upstream of the transcription start site, entirely
      within the NCR, while the CPm control region mapped within a 57 nt sequence
      within the upstream ORF. Although both regions were predicted to fold into two
      stem-loop structures, mutagenesis suggested that primary structure might be more
      important than the secondary structure. Because each controller element produced
      large amounts of 3'-terminal positive- and negative-stranded sgRNAs, we could not
      differentiate whether the cis-acting element functioned as a promoter or
      terminator, or both. Reversal of the control element unexpectedly produced large
      amounts of a negative-stranded sgRNA apparently by termination of negative
      stranded genomic RNA synthesis. Further examination of controller elements in
      their native orientation showed normal production of abundant amounts of positive
      stranded sgRNAs extending to near the 5'-terminus, corresponding to termination
      at each controller element. Thus, each controller element produced three sgRNAs,
      a 5'-terminal positive strand and both positive- and negative-stranded 3'
      terminal RNAs. Therefore, theoretically CTV could produce 30-33 species of RNAs
      in infected cells.

PMID- 11448168
TI  - Inhibition of cellular functions of HIV-1 Nef by artificial SH3 domains.
AB  - SH3 domains regulate many normal and pathological cellular processes by guiding
      specific protein interactions. Studies on binding of HIV-1 Nef to the SH3 domain
      of the Hck tyrosine kinase have indicated an important role for the SH3 RT-loop
      region in ligand binding. Here we have tested the potential of artificial Hck
      derived SH3 domains carrying tailored RT-loops providing high affinity for Nef as
      intracellular inhibitors of Nef. These artificial SH3 domains efficiently
      associated with Nef in cells and thereby potently inhibited SH3-dependent Nef
      functions, such as association with p21-activated kinase-2 and induction of the
      transcription factor NFAT. On the other hand, biochemical and functional data
      indicated that the Nef-targeted SH3 domains were not prone to compete with normal
      SH3-mediated processes. Thus, RT-loop-modified SH3 domains represent a novel
      approach for selectively interfering with cellular signaling events, which could
      be exploited in research as well as in therapeutic applications.

PMID- 11448169
TI  - B-cell-mediated lysis of cells infected with the neurotropic JHM strain of mouse
      hepatitis virus.
AB  - Cells expressing the spike (S) glycoprotein of the neurotropic JHM strain (JHMV)
      of mouse hepatitis virus (MHV) are susceptible to lysis by B cells derived from
      naive mice, including B cells from perforin-deficient mice. Cytolysis requires
      interaction of the virus receptor and the viral S glycoprotein, is independent of
      other viral-induced components, and is not a unique property of B cells.
      Neutralizing anti-S-protein monoclonal antibodies (mAb) and a mAb specific for
      the viral receptor inhibit lysis. However, cells infected with an MHV strain
      unable to induce cell-cell fusion are resistant to lysis and lysis of JHMV
      infected cells is inhibited by an anti-S-protein nonneutralizing mAb which
      prevents S-protein-mediated cell fusion. These data suggest that B cells may
      function as antibody-independent innate immune response during JHMV infection in
      vivo.

PMID- 11448170
TI  - The AG recombinant IbNG and novel strains of group M HIV-1 are common in
      Cameroon.
AB  - The genetic diversity of group M HIV-1 is highest in west central Africa. Blood
      samples from four locations in Cameroon were collected to determine the molecular
      epidemiology of HIV-1. The C2-V5 region of envelope was sequenced from 39 of the
      40 samples collected, and 7 samples were sequenced across the genome. All strains
      belonged to group M of HIV-1. The circulating recombinant form CRF02 AG (IbNG)
      was the most common strain (22/39, 56%). Two of these were confirmed by full
      genome analysis. Four samples (4/39, 10%) clustered with the sub-subtype F2 and
      one of these was confirmed by full genome sequencing. Recombinant forms, each
      different but containing subtype A, accounted for the next most common form
      (7/39, 18%). Among these recombinants, those combining subtypes A and G were the
      most common (4/7, 57%). Also found were 3 subtype A, 2 subtype G, and 1 subtype B
      strain. Many recombination break points were shared between IbNG and the other AG
      recombinants, though none of these other AG recombinants included IbNG as a
      parent. This suggests that there was an ancestral AG recombinant that gave rise
      to CRF02 AG (IbNG), the successful circulating recombinant form, and to others
      that were less successful and are now rare.

PMID- 11448171
TI  - Analysis of the first complete DNA sequence of an invertebrate iridovirus: coding
      strategy of the genome of Chilo iridescent virus.
AB  - Chilo iridescent virus (CIV), the type species of the genus Iridovirus, a member
      of the Iridoviridae family, is highly pathogenic for a variety of insect larvae.
      The virions contain a single linear ds DNA molecule that is circularly permuted
      and terminally redundant. The coding capacity and strategy of the CIV genome was
      elucidated by the analysis of the complete DNA nucleotide sequence of the viral
      genome (212,482 bp) using cycle sequencing by primer walking technology. Both DNA
      strands were sequenced independently and the average redundancy for each
      nucleotide was found to be 1.85. The base composition of the viral genomic DNA
      sequence was found to be 71.37% A+T and 28.63% G+C. The CIV genome contains 468
      open reading frames (ORFs). The size of the individual viral gene products ranges
      between 40 and 2432 amino acids. The analysis of the coding capacity of the CIV
      genome revealed that 50% (234 ORFs) of all identified ORFs were nonoverlapping.
      The comparison of the deduced amino acid sequences to entries in protein data
      banks led to the identification of several genes with significant homologies,
      such as the two major subunits of the DNA-dependent RNA polymerase, DNA
      polymerase, protein kinase, thymidine and thymidylate kinase, thymidylate
      synthase, ribonucleoside-diphosphate reductase, major capsid protein, and others.
      The highest homologies were detected between putative viral gene products of CIV
      and lymphocystis disease virus of fish (LCDV). Although many CIV putative gene
      products showed significant homologies to the corresponding viral proteins of
      LCDV, no colinearity was detected when the coding strategies of the CIV and LCDV
      1 were compared to each other. An intriguing result was the detection of a viral
      peptide of 53 amino acid residues (ORF 160L) showing high homology
      (identity/similarity: 60.0%/30.0%) to sillucin, an antibiotic peptide encoded by
      Rhizomucor pusillus. Iridovirus homologs of cellular genes possess particular
      implications for the molecular evolution of large DNA viruses.

PMID- 11448172
TI  - Type I IFN modulates the immune response induced by DNA vaccination to
      pseudorabies virus glycoprotein C.
AB  - DNA vaccines have the capacity to induce strong Th1-biased immune responses that
      are of major importance to providing protection against intracellular pathogens.
      In the present study we have focused on the role played by type I IFN in immune
      responses induced after DNA vaccination. Mice lacking the IFNAR1 chain of the
      type I IFN receptor (IFNAR K/O mice) were immunized with a plasmid encoding
      glycoprotein C of pseudorabies virus (PRV-gC). After DNA vaccination, wild-type
      (WT) mice showed features characteristic of Th1 immune responses, such as high
      IgG2a:IgG1 anti-PRV Ab ratio and antigen-specific IFN-gamma production by spleen
      cells. In contrast, IFNAR K/O mice showed a significantly lower IgG2a:IgG1 Ab
      ratio and IFN-gamma production. In addition, the percentage of CD8(+) and B lymph
      node cells expressing CD69 after PRV-gC DNA vaccination was lower in IFNAR K/O
      than in WT mice. These results support a major role played by type I IFN in
      shaping Th1 immune responses after DNA vaccination. Codelivery of plasmids
      encoding IL-12 and IL-18 along with the plasmid encoding PRV-gC restored Th1
      responses in IFNAR K/O mice.

PMID- 11448173
TI  - Highly sulfated forms of heparin sulfate are involved in japanese encephalitis
      virus infection.
AB  - Japanese encephalitis virus (JEV) infects a broad range of cell types in vitro,
      though little is known about the initial events of JEV infection. In the present
      study, we found that highly sulfated glycosaminoglycans (GAGs) are involved in
      infection of both neurovirulent (RP-9) and attenuated (RP-2ms) JEV strains.
      Competition experiments using highly sulfated GAGs, heparin and dextran sulfate,
      demonstrated an inhibition of JEV's attachment and subsequent infection of BHK-21
      cells. Treatment of target cells by a potent sulfation inhibitor, sodium
      chlorate, greatly reduced viral binding ability as well as infection, suggesting
      a critical role of GAGs' sulfation status on the cellular surface in JEV
      infection. This phenomenon was confirmed by the manifestation of a distinct
      binding efficiency of JEV to the wild-type CHO cell line and its mutants with
      defects in GAG biosynthesis. We also demonstrated the binding of JEV particles
      and virus envelope glycoprotein to immobilized heparin beads. Furthermore, the
      addition of heparin suppressed the cytopathic effects induced by JEV infection in
      cultured cells. Our results establish that the highly sulfated form of GAGs on
      cell surfaces plays a determining role in the early stage of in vitro JEV
      infection.

PMID- 11448174
TI  - Ty1 retrotransposition and programmed +1 ribosomal frameshifting require the
      integrity of the protein synthetic translocation step.
AB  - Programmed ribosomal frameshifting is utilized by a number of RNA viruses to
      ensure the correct ratio of viral structural to enzymatic proteins for viral
      particle assembly. Altering frameshifting efficiencies upsets this ratio,
      inhibiting virus propagation. Two yeast viruses that induce host cell ribosomes
      to shift translational reading frame were used as tools to explore the
      interactions between viruses and host cellular protein synthetic machinery.
      Previous studies showed that the ribosome-inactivating protein pokeweed antiviral
      protein specifically inhibited propagation of the Ty1 retrotransposable element
      of yeast as a consequence of inhibition of programmed +1 ribosomal frameshifting.
      Here, complementary genetic and pharmacological approaches were employed to test
      whether inhibition of Ty1 retrotransposition is a general feature of alterations
      in the translocation step of elongation and +1 frameshifting. The results
      demonstrate that cells harboring a variety of mutant alleles of two host-encoded
      proteins that are involved in translocation, eukaryotic elongation factor-2 and
      the ribosome-associated protein RPP0, have Ty1 propagation defects. We also show
      that sordarin, a fungus-specific inhibitor of eEF-2 function, specifically
      inhibits programmed +1 ribosomal frameshifting and Ty1 retrotransposition. These
      findings serve to link inhibition of Ty1 retrotransposition and +1 frameshifting
      to changes in the translocation step of elongation.

PMID- 11448175
TI  - Nef is required for efficient HIV-1 replication in cocultures of dendritic cells
      and lymphocytes.
AB  - Dendritic cells (DCs) are thought to play a crucial role in the pathogenesis of
      HIV-1 infection. DCs are believed to transport virus particles to lymph nodes
      before transfer to CD4(+) lymphocytes. We have investigated the role of Nef in
      these processes. HIV-1 replication was examined in human immature DC-lymphocyte
      cocultures and in DCs or lymphocytes separately. Using various R5-tropic and X4
      tropic HIV-1 strains and their nef-deleted (Deltanef) counterparts, we show that
      Nef is required for optimal viral replication in immature DC-T cells clusters and
      in T lymphocytes. Nef exerts only a marginal role on viral replication in
      immature DCs alone as well as on virion capture by DCs, long-term intracellular
      accumulation and transmission of X4 strains to lymphocytes. We also show that
      wild-type and Deltanef virions are similarly processed for MHC-I restricted
      exogenous presentation by DCs. Taken together, these results help explain how HIV
      1 Nef may affect viral spread and immune responses in the infected host.

PMID- 11448176
TI  - Molecular characterizations of the equine herpesvirus 1 ETIF promoter region and
      translation initiation site.
AB  - The equine herpesvirus 1 (EHV-1) homolog of the herpes simplex virus type 1 (HSV
      1) tegument phosphoprotein, alphaTIF (Vmw65; VP16), was identified previously as
      the product of open reading frame 12 (ORF12), was shown to trans-activate
      immediate-early (IE) gene promoters, and was described as a 60-kDa virion
      component designated ETIF. However, the ETIF promoter region and transcription
      initiation site were not identified. The poly(A) signal of the gene 11 (UL49
      homolog) lies just upstream of the first ETIF translation initiation codon,
      indicating that the first ATG may not be used for initiating ETIF translation.
      Another in-frame translation initiation codon (ATG2) is located 88 bp downstream
      of the first ETIF initiation codon (ATG1). Western blot analysis showed that the
      expressed ETIF protein migrated in SDS-PAGE with an apparent molecular mass of
      approximately 56 kDa, the same molecular weight identified in SDS-PAGE analysis
      of the KyD EHV-1 virion preparations. The ETIF expression vector pCETIF, which
      contains ATG2, trans-activated the IE promoter more efficiently than the pC12
      containing both ATG1 and ATG2. S1 nuclease analyses mapped the 5' initiation site
      of the 1.4-kb transcript approximately 17 to 21 nt downstream of the ATG1. The
      nucleotide sequence upstream of the ATG1 did not have any promoter activity,
      while the nucleotide sequence upstream of the ATG2 had promoter activity. In
      transient transfection assays, the pETIFM2 vector, which was mutated in the ATG2,
      did not trans-activate the IE promoter; however, the pETIFM1 vector, which was
      mutated in the ATG1, trans-activated the IE promoter. These results demonstrated
      that the ATG2 of the ETIF ORF is the ETIF translation initiation codon. ETIF
      trans-activated only the IE promoter, not early (EICP0, EICP22, EICP27, and
      thymidine kinase) or late (IR5) promoters, confirming that EICP0, EICP22, and
      EICP27 are early genes.

PMID- 11448177
TI  - Reevaluation of stereoelectronic contributions to the conformational properties
      of the phosphodiester and N3'-phosphoramidate moieties of nucleic acids.
AB  - The anomeric effect in the phosphodiester backbone of nucleic acids is a
      stereoelectronic effect that has conventionally been linked to interactions
      between lone pairs on the O(ester) atoms and P-O(ester) antibonding orbitals. The
      present study demonstrates that the anomeric effect in the phosphodiester
      backbone is significantly more complex than portrayed by this description. The
      presence of multiple lone pairs and antibonding orbitals around the phosphorus
      atom leads to additional contributions to the anomeric effect, especially
      involving the anionic oxygen lone pairs. On the basis of the structural changes
      and Natural Bond Orbital analysis it is shown that a complex balance between
      stereoelectronic effects involving both the ester and anionic oxygen lone pairs
      governs the conformational properties of the phosphodiester backbone. The N3'
      phosphoramidate DNA backbone differs from the phosphodiester backbone due to the
      N3'-H moiety having only a single lone pair instead of the two lone pairs present
      on the O3' atom substituted. The present study uses N3'-phosphoramidate as a
      control to understand the changes in stereoelectronic effects as a result of
      changes in the structure and conformation. Two previously uncharacterized
      properties of the N3'-phosphoramidate backbone are also observed and explained
      through the complex balance of the postulated electronic delocalizations. The
      first observation is that the N3'-H moiety in N3'-phosphoramidate is a flexible
      moiety that can change the orientation of its hydrogen through inversion without
      a significant energetic penalty in both the gas phase and the aqueous phase. The
      second observation is that the stabilization of the C3'-endo conformation in N3'
      phosphoramidate is primarily due to aqueous solvation rather than intrinsic gas
      phase effects involving the reduced electronegativity of the 3'-substituent.

PMID- 11448178
TI  - Mechanistic investigation of UDP-galactopyranose mutase from Escherichia coli
      using 2- and 3-fluorinated UDP-galactofuranose as probes.
AB  - The galactofuranose moiety found in many surface constituents of microorganisms
      is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction
      reaction catalyzed by UDP-Galp mutase. This enzyme, which has been isolated from
      several bacterial sources, is a flavoprotein. To study this catalysis, the cloned
      Escherichia coli mutase was purified and two fluorinated analogues, UDP-[2-F]Galf
      (9) and UDP-[3-F]Galf (10), were chemically synthesized. These two compounds were
      found to be substrates for the reduced UDP-Galp mutase with the Km values
      determined to be 65 and 861 microM for 9 and 10, respectively, and the
      corresponding kcat values estimated to be 0.033 and 5.7 s(-1). Since the fluorine
      substituent is redox inert, a mechanism initiated by the oxidation of 2-OH or 3
      OH on the galactose moiety can thus be firmly ruled out. Furthermore, both 9 and
      10 are poorer substrates than UDP-Galf, and the rate reduction for 9 is
      especially significant. This finding may be ascribed to the inductive effect of
      the 2-F substituent that is immediately adjacent to the anomeric center, and is
      consistent with a mechanism involving formation of oxocarbenium intermediates or
      transition states during turnover. Interestingly, under nonreducing conditions,
      compounds 9 and 10 are not substrates, but instead are inhibitors for the mutase.
      The inactivation by 10 is time-dependent, active-site-directed, and irreversible
      with a K(I) of 270 microM and a k(inact) of 0.19 min(-1). Since the K(I) value is
      similar to Km, the observed inactivation is unlikely a result of tight binding.
      To our surprise, the inactivated enzyme could be regenerated in the presence of
      dithionite, and the reduced enzyme is resistant to inactivation by these
      fluorinated analogues. It is possible that reduction of the enzyme-bound FAD may
      induce a conformational change that facilitates the breakdown of the putative
      covalent enzyme-inhibitor adduct to reactivate the enzyme. It is also conceivable
      that the reduced flavin bears a higher electron density at N-1, which may play a
      role in preventing the formation of the covalent adduct or facilitating its
      breakdown by charge stabilization of the oxocarbenium intermediates/transition
      states. Clearly, this study has led to the identification of a potent inactivator
      (10) for this enzyme, and study of its inactivation has also shed light on the
      possible mechanism of this mutase.

PMID- 11448181
TI  - Peptoid oligomers with alpha-chiral, aromatic side chains: sequence requirements
      for the formation of stable peptoid helices.
AB  - The achiral backbone of oligo-N-substituted glycines or "peptoids" lacks hydrogen
      bond donors, effectively preventing formation of the regular, intrachain hydrogen
      bonds that stabilize peptide alpha-helical structures. Yet, when peptoids are N
      substituted with alpha-chiral, aromatic side chains, oligomers with as few as
      five residues form stable, chiral, polyproline-like helices in either organic or
      aqueous solution. The adoption of chiral secondary structure in peptoid oligomers
      is primarily driven by the steric influence of these bulky, chiral side chains.
      Interestingly, peptoid helices of this class exhibit intense circular dichroism
      (CD) spectra that closely resemble those of peptide alpha-helices. Here, we have
      taken advantage of this distinctive spectroscopic signature to investigate
      sequence-related factors that favor and disfavor stable formation of peptoid
      helices of this class, through a comparison of more than 30 different
      heterooligomers with mixed chiral and achiral side chains. For this family of
      peptoids, we observe that a composition of at least 50% alpha-chiral, aromatic
      residues is necessary for the formation of stable helical structure in hexameric
      sequences. Moreover, both CD and 1H-13C HSQC NMR studies reveal that these short
      peptoid helices are stabilized by the placement of an alpha-chiral, aromatic
      residue on the carboxy terminus. Additional stabilization can be provided by the
      presence of an "aromatic face" on the helix, which can be patterned by
      positioning aromatic residues with three-fold periodicity in the sequence.
      Extending heterooligomer chain length beyond 12-15 residues minimizes the impact
      of the placement, but not the percentage, of alpha-chiral aromatic side chains on
      overall helical stability. In light of these new data, we discuss implications
      for the design of helical, biomimetic peptoids based on this structural motif.

PMID- 11448182
TI  - New insights on the mechanisms of the pH-independent reactions of benzo[a]pyrenes
      7,8-diol 9,10-epoxides.
AB  - The rates and products of the reactions of (+/-)-7beta,8alpha-dihydroxy
      9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (1) and (+/-)-7beta,8alpha
      dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (2) in water and
      dioxane-water mixtures have been determined over a pH range wider than that of
      earlier studies. This study provides additional insight on the mechanisms of the
      pH-independent reactions of 1 and 2. The rate profile for reaction of 1 shows
      acid-catalyzed hydrolysis at pH <5, a rate plateau at pH 5-9.5, a negative
      inflection at pH 10-11.5, and a rate increase at pH >11.5. The rate decrease
      between pH 10 and pH 11.5 is accompanied by a decrease in the yield of tetrols
      from 60% (pH 8) to 29% (pH 11.2) and is interpreted to be the result of a partial
      change in mechanism brought about by attack of hydroxide ion acting as a base to
      deprotonate a carbocation intermediate and regenerate 1 at pH >10, thus reducing
      the contribution of the pathway for tetrol formation in which water attacks the
      carbocation. The rate profile for the reaction of 2 exhibits only a single rate
      plateau at intermediate pH, along with increases in rate at low and high pH
      because of second-order reactions of 2 with H+ and HO-, respectively. The lack of
      a rate depression at pH >10 and the product studies for the reaction of 2 in
      dilute sodium azide solutions suggest that the tetrol-forming reactions of the pH
      independent reaction of 2 are concerted or near-concerted.

PMID- 11448183
TI  - Hierarchical self-assembly of chiral complementary hydrogen-bond networks in
      water: reconstitution of supramolecular membranes.
AB  - Spontaneous formation of complementary hydrogen-bond pairs and their hierarchical
      self-assembly (reconstitution) into chiral supramolecular membranes are achieved
      in water by mixing amphiphilic pairs of glutamate-derived melamine 6 and ammonium
      derivatized azobenzene cyanuric acid 4. Electron microscopy is used to observe
      formation of helical superstructures, which are distinct from the aggregate
      structures observed for each of the single components in water. In addition, a
      spectral blue-shift and induced circular dichroism (ICD) with exciton coupling
      are observed for the pi-pi* absorption of the azobenzene chromophores. These
      observations are consistent with the reconstitution of the hydrogen-bond-mediated
      supramolecular membrane 6-4. Spectral titration experiments indicate the
      stoichiometric integration of the complementary subunits with an association
      constant of 1.13 x 10(5) M(-1). This value is considerably larger than those
      reported for the artificial hydrogen-bonding complexes in aqueous media. The
      remarkable reconstitution efficiency is ascribed to the hydrophobically driven
      self-organization of the amphiphilic, linear hydrogen-bond networks in water.
      Molecular structure of the complementary subunits plays an important role in the
      complexation process since it is restricted by the photoisomerized cis-azobenzene
      subunit. On the other hand, thermally regenerated trans-isomer 4 undergoes facile
      complexation with the counterpart 6. The present reconstitution of supramolecular
      membranes provides the first example of complementary hydrogen-bond-directed
      formation of soluble, mesoscopic supramolecular assemblies in water.

PMID- 11448184
TI  - Catalytic enantioselective Reissert-type reaction: development and application to
      the synthesis of a potent NMDA receptor antagonist (-)-L-689,560 using a solid
      supported catalyst.
AB  - Full details of the first catalytic enantioselective Reissert-type reaction are
      described. Utilizing the Lewis acid-Lewis base bifunctional catalyst 5 or 6 (9
      mol %), the Reissert products were obtained in 57 to 99% yield with 54 to 96% ee.
      Electron-rich quinolines produced better yields and enantioselectivities than
      electron-deficient substrates. Kinetic studies indicated that the reaction should
      proceed via the rate-determining acyl quinolinium formation, followed by the
      attack of a cyanide. The catalyst does not facilitate the first rate-determining
      step; however, it strongly facilitates the second cyanation step. The reaction
      was successfully applied to an efficient catalytic asymmetric synthesis of a
      potent NMDA receptor antagonist (-)-L-689,560. A key step is the one-pot process
      using the Reissert-type reaction from quinoline 1f, followed by stereoselective
      reduction of the resulting enamine 2f. This step gave the key intermediate 20 in
      91% yield with 93% ee, using 1 mol % of 6. The enantiomerically pure target
      compound was obtained through 10 operations (including recrystallization) in
      total yield of 47%. Furthermore, 6 was immobilized to JandaJEL, and the resulting
      solid-supported catalyst 11 afforded 20 in a comparable yield to the homogeneous
      6, but with slightly lower enantioselectivity.

PMID- 11448186
TI  - Why are the hydroxy groups of partially protected N-acetylglucosamine derivatives
      such poor glycosyl acceptors, and what can be done about it? A comparative study
      of the reactivity of N-acetyl-, N-phthalimido-, and 2-azido-2-deoxy-glucosamine
      derivatives in glycosylation. 2-Picolinyl ethers as reactivity-enhancing
      replacements for benzyl ethers.
AB  - Competition experiments were used to determine that the 4-OH of a 2-deoxy-2
      azidoglucose derivative is more reactive than that of the corresponding N
      phthalimido glucose derivative which, in turn, is more easily glycosylated than
      the N-acetyl derivative. Glycosylation of the 4-OH groups of the N,N-diacetyl and
      N-acetyl-N-benzyl glucosamine was also found to be superior to that of the simple
      N-acetyl substance. The 3-O-picolinyl ether of a 4,6-O-benzylidene-protected N
      acetylglucosamine was shown to have a strong intramolecular hydrogen bond to the
      adjacent acetamide group. This interaction does not persist in the 3-O-picolinyl
      6-O-benzyl N-acetylglucosamine derivative, owing to a probable competing hydrogen
      bond between the 4-OH and the picolinyl ether. However, in the 3-O-picolinyl-4-O
      benzyl N-acetylglucosamine regioisomer the picolinyl-acetamide hydrogen bond
      persists and leads to an enhancement of reactivity of the 6-OH, over and above
      that in the corresponding 3-O-benzyl ether, due to disruption of the typical
      intermolecular amide hydrogen bonding scheme. It is demonstrated that the
      picolinyl ether is readily removed by hydrogenolysis at atmospheric pressure and
      room temperature.

PMID- 11448187
TI  - Efficient and selective aerobic oxidation of alcohols into aldehydes and ketones
      using ruthenium/TEMPO as the catalytic system.
AB  - The combination of RuCl2(PPh3)3 and TEMPO affords an efficient catalytic system
      for the aerobic oxidation of a variety of primary and secondary alcohols, giving
      the corresponding aldehydes and ketones, in >99% selectivity in all cases. The
      Ru/TEMPO system displayed a preference for primary vs secondary alcohols. Results
      from Hammett correlation studies (rho = -0.58) and the primary kinetic isotope
      effect (kH/kD = 5.1) for the catalytic aerobic benzyl alcohol oxidations are
      inconsistent with either an oxoruthenium (O=Ru) or an oxoammonium based
      mechanism. We postulate a hydridometal mechanism, involving a "RuH2(PPh3)3"
      species as the active catalyst. TEMPO acts as a hydrogen transfer mediator and is
      either regenerated by oxygen, under catalytic aerobic conditions, or converted to
      TEMPH under stoichiometric anaerobic conditions.

PMID- 11448195
TI  - Chi1 torsion angle dynamics in proteins from dipolar couplings.
AB  - Experiments are presented for the measurement of one-bond carbon-proton dipolar
      coupling values at CH and CH2 ositions in 13C-labeled, approximately 50%
      fractionally deuterated proteins. 13Cbeta-1Hbeta dipolar couplings have been
      measured for 38 of 49 possible residues in the 63-amino-acid B1 domain of
      peptostreptococcal protein L in two aligning media and interpreted in the context
      of side-chain chi1 torsion angle dynamics. The beta protons for 18 of the 25 beta
      methylene-containing amino acids for which dipolar data are available can be
      unambiguously stereoassigned, and for those residues which are best fit to a
      single rotamer model the chi(1) angles obtained deviate from crystal structure
      values by only 5.2 degrees (rmsd). The results for 11 other residues are
      significantly better fit by a model that assumes jumps between the three
      canonical (chi1 approximately -60 degrees, 60 degrees, 180 degrees ) rotamers.
      Relative populations of the rotamers are determined to within +/-6% uncertainty
      on average and correlate with dihedral angles observed for the three molecules in
      the crystal asymmetric unit. Entropic penalties for quenching chi1 jumps are
      considered for six mobile residues thought to be involved in binding to human
      immunoglobulins. This study demonstrates that dipolar couplings may be used to
      characterize both the conformation of static residues and side-chain motion with
      high precision.

PMID- 11448199
TI  - Three different fates for phosphinidenes generated by photocleavage of phospha
      Wittig reagents Arp=PMe3.

PMID- 11448201
TI  - The conformations of discodermolide in DMSO.

PMID- 11448203
TI  - The influence of cyanide on the carbonylation of iron(II): synthesis of Fe-Sr-Cn
      Co centers related to the hydrogenase active sites.

PMID- 11448205
TI  - General strategies for the synthesis of the major classes of C-aryl glycosides.

PMID- 11448206
TI  - C2-acyloxyglycosylation with glycal donors.

PMID- 11448208
TI  - Micropatterning biological molecules on a polymer surface using elastomeric
      microwells.

PMID- 11448209
TI  - Coupled oxidation of heme by myoglobin is mediated by exogenous peroxide.

PMID- 11448212
TI  - Effect of temperature and composition on the formation of nanoscale compartments
      in phospholipid membranes.

PMID- 11448213
TI  - Ultrafast electron-transfer reactions between thionine and guanosine bases.

PMID- 11448217
TI  - The generality of DNA-templated synthesis as a basis for evolving non-natural
      small molecules.

PMID- 11448219
TI  - Reversible carnitine palmitoyltransferase inhibitors with broad chemical
      diversity as potential antidiabetic agents.
AB  - A series of carnitine related compounds of general formula XCH(2)CHZRCH(2)Y were
      evaluated as CPT I inhibitors in intact rat liver (L-CPT I) and heart
      mitochondria (M-CPT I). Derivative 27 (ZR = -HNSO(2)R, R = C(12), X =
      trimethylammonium, Y = carboxylate, (R) form) showed the highest activity (IC(50)
      = 0.7 microM) along with a good selectivity (M-CPT I/L-CPTI IC(50) ratio = 4.86).
      Diabetic db/db mice treated orally with 27 showed a significant reduction of
      serum glucose levels.

PMID- 11448220
TI  - Novel C-terminus modifications of the Dmt-Tic motif: a new class of dipeptide
      analogues showing altered pharmacological profiles toward the opioid receptors.
AB  - The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic
      dipeptide analogues are described. These resulting analogues bearing different C
      terminal functionalities were found to bind to the human delta receptor with high
      affinity. One specific class of dipeptides bearing urea/thiourea functionalities
      showed partial to full activation of the delta receptor. Several dipeptides also
      showed good binding affinities with full activation of the human kappa receptor,
      a novel property for those ligands.

PMID- 11448221
TI  - Design, synthesis, computational prediction, and biological evaluation of ester
      soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii.
AB  - A series of lipophilic soft drugs structurally related to the nonclassical
      dihydrofolate reductase (DHFR) inhibitors trimetrexate and piritrexim have been
      designed, synthesized, and evaluated in DHFR assays, with special emphasis on the
      inhibition of P. carinii DHFR. The best inhibitors, encompassing an ester bond in
      the bridge connecting the two aromatic systems, were approximately 10 times less
      potent than trimetrexate and piritrexim. The metabolites were designed to be poor
      inhibitors. Furthermore, molecular dynamics simulations of three ligands in
      complex with DHFR from Pneumocystis carinii and from the human enzyme were
      conducted in order to better understand the factors determining the selectivity.
      A correct ranking of the relative inhibition of DHFR was achieved utilizing the
      linear interaction energy method. The soft drugs are intended for local
      administration. One representative ester was selected for a pharmacokinetic study
      in rats where it was found to undergo fast metabolic degradation to the predicted
      inactive metabolites.

PMID- 11448222
TI  - Phenylpiperazinylalkylamino substituted pyridazinones as potent alpha(1)
      adrenoceptor antagonists.
AB  - QSAR models have been used for designing a series of compounds characterized by a
      N-phenylpiperazinylalkylamino moiety linked to substituted pyridazinones, which
      have been synthesized. Measurements of the binding affinities of the new
      compounds toward the alpha(1a)-, alpha(1b)-, and alpha(1d)-AR cloned subtypes as
      well as the 5-HT(1A) receptor have been done validating, at least in part, the
      estimations of the theoretical models. This study provides insight into the
      structure activity relationships of the alpha(1)-ARs ligands and their alpha(1)
      AR/5-HT(1A) selectivity.

PMID- 11448223
TI  - Volume learning algorithm artificial neural networks for 3D QSAR studies.
AB  - The current study introduces a new method, the volume learning algorithm (VLA),
      for the investigation of three-dimensional quantitative structure-activity
      relationships (QSAR) of chemical compounds. This method incorporates the
      advantages of comparative molecular field analysis (CoMFA) and artificial neural
      network approaches. VLA is a combination of supervised and unsupervised neural
      networks applied to solve the same problem. The supervised algorithm is a feed
      forward neural network trained with a back-propagation algorithm while the
      unsupervised network is a self-organizing map of Kohonen. The use of both of
      these algorithms makes it possible to cluster the input CoMFA field variables and
      to use only a small number of the most relevant parameters to correlate spatial
      properties of the molecules with their activity. The statistical coefficients
      calculated by the proposed algorithm for cannabimimetic aminoalkyl indoles were
      comparable to, or improved, in comparison to the original study using the partial
      least squares algorithm. The results of the algorithm can be visualized and
      easily interpreted. Thus, VLA is a new convenient tool for three-dimensional QSAR
      studies.

PMID- 11448224
TI  - Nonpeptidic, monocharged, cell permeable ligands for the p56lck SH2 domain.
AB  - p56lck is a member of the src family of tyrosine kinases and plays a critical
      role in the signal transduction events that lead to T cell activation. Ligands
      for the p56lck SH2 domain have the potential to disrupt the interaction of p56lck
      with its substrates and derail the signaling cascade that leads to the production
      of cytokines such as interleukin-2. Starting from the quintuply charged (at
      physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J.
      Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the
      modified dipeptide 3, which carries just two charges at physiological pH. Here we
      present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This
      molecule displays good binding affinity for the p56lck SH2 domain (K(d) 1 microM)
      and good cell permeation, and this combination of properties allowed us to
      demonstrate clear-cut inhibitory effects on a very early event in T cell
      activation, namely calcium mobilization.

PMID- 11448225
TI  - Discriminating between drugs and nondrugs by prediction of activity spectra for
      substances (PASS).
AB  - Using the computer system PASS (prediction of activity spectra for substances),
      which predicts simultaneously several hundreds of biological activities, a
      training set for discriminating between drugs and nondrugs is created. For the
      training set, two subsets of databases of drugs and nondrugs (a subset of the
      World Drug Index, WDI, vs the Available Chemicals Directory, ACD) are used. The
      high value of prediction accuracy shows that the chemical descriptors and
      algorithms used in PASS provide highly robust structure-activity relationships
      and reliable predictions. Compared to other methods applied in this field, the
      direct benchmark undertaken with this paper showed that the results obtained with
      PASS are in good accordance with these approaches. In addition, it has been shown
      that the more specific drug information used in the training set of PASS, the
      more specific discrimination between drug and nondrug can be obtained.

PMID- 11448226
TI  - Potent dibasic GPIIb/IIIa antagonists with reduced prolongation of bleeding time:
      synthesis and pharmacological evaluation of 2-oxopiperazine derivatives.
AB  - A series of 2-oxopiperazine derivatives, possessing basic moieties at the 3- and
      the 4-positions, were synthesized and evaluated for their abilities to inhibit
      platelet aggregation and for their effects on bleeding time. Among the compounds,
      2-[(3S)-4-[2-[(4-guanidinobenzoyl)amino]acetyl]-3-[3-[(4
      guanidinobenzoyl)amino]propyl]-2-oxopiperazinyl]acetic acid (12c) showed a potent
      inhibitory effect on platelet aggregation and good dissociation between the
      efficacy and the bleeding side effect. Intravenous infusion of compound 12c at
      1.6 microg/mL/min completely prevented arterial thrombus formation induced by
      endothelial injury in guinea pigs. The dose of 12c that prolonged the bleeding
      time to three times the control value was 5.8 microg/mL/min. These results
      suggest that compound 12c might be useful in the clinical treatment of thrombotic
      diseases, and we selected 12c (TAK-024) as a candidate for the clinical trials.

PMID- 11448227
TI  - Synthesis and evaluation of hydroxylated polyamine analogues as
      antiproliferatives.
AB  - A new means of accessing N(1)-cyclopropylmethyl-N(11)-ethylnorspermine (CPMENSPM)
      and the first synthesis of (2R,10S)-N(1)-cyclopropylmethyl-2,10-dihydroxy-N(11)
      ethylnorspermine [(2R,10S)-(HO)(2)CPMENSPM] are described. Both of these
      polyamine analogues are shown to be more active against L1210 murine leukemia
      cell growth than either N(1),N(11)-diethylnorspermine (DENSPM) or (2R,10R)
      N(1),N(11)-diethyl-2,10-dihydroxynorspermine [(2R,10R)-(HO)(2)DENSPM] after 96 h
      of treatment; the activity was comparable to that of (2S,10S)-N(1),N(11)-diethyl
      2,10-dihydroxynorspermine [(2S,10S)-(HO)(2)DENSPM] at 96 h. Both cyclopropyl
      compounds reduced putrescine and spermidine pools, but less effectively than did
      DENSPM and its derivatives. Only CPMENSPM, and not (2R,10S)-(HO)(2)CPMENSPM,
      lowered spermine pools. As with DENSPM and (2R,10R)-(HO)(2)DENSPM, both
      cyclopropyl analogues diminished ornithine decarboxylase and S-adenosylmethionine
      decarboxylase activity. Unlike the hydroxylated DENSPM compounds, both
      cyclopropyl norspermines substantially upregulated spermidine/spermine N(1)
      acetyltransferase. The most interesting effect of hydroxylating CPMENSPM is the
      profound reduction in toxicity compared with that of the parent drug. The same
      phenomenon had been observed for the DENSPM/(2R,10R)-(HO)(2)DENSPM pair. Thus,
      hydroxylation of norspermine analogues appears to be a way to maintain the
      compounds' antiproliferative activity while reducing their toxicity.

PMID- 11448228
TI  - Peptide folding induces high and selective affinity of a linear and small beta
      peptide to the human somatostatin receptor 4.
AB  - beta-Peptides with side chains in the 2- and 3-positions on neighboring residues
      (of (S) configuration) are known to fold and form a turn (similar to an alpha
      peptidic beta-turn). Thus, we have synthesized an appropriately substituted beta
      tetrapeptide derivative to mimic the hormone somatostatin in its binding to the
      human receptors hsst(1-5), which is known to rest upon a turn containing the
      amino acid residues Thr, Lys, Trp, and Phe. The N-acetyl-peptide amide Ac-beta(3)
      HThr-beta(2)-HLys-beta(3)-HTrp-beta(3)-HPhe-NH(2) (1) indeed shows all
      characteristics of the targeted turn-mimic: Lys CH(2) groups are in the shielding
      cone of the Trp indole ring (by NMR analysis, Figure 2) and there is high and
      specific nanomolar affinity for hsst(4) receptor (Table 1). In contrast, the
      isomer 2 bearing the Lys side chain in 3-, rather than in the 2-position, has a
      1000-fold smaller affinity to hsst(4). The syntheses of the required Fmoc
      protected beta-amino acids (8-11, 17) are described (Schemes 1-3). Coupling of
      the beta-amino acids was achieved by the manual solid-phase technique, on Rink
      resin.

PMID- 11448229
TI  - Significance of asymmetric sites in choosing siderophores as deferration agents.
AB  - The syntheses of the microbial iron chelators L-fluviabactin, its unnatural
      enantiomer, D-fluviabactin, L-homofluviabactin, and L-agrobactin, are described.
      The key steps involve the selective bis-acylation of the terminal nitrogens of
      norspermidine, spermidine, or homospermidine with 2,3-bis(benzyloxy)benzoic acid
      in the presence of 1,1-carbonyldiimidazole, followed by coupling of the N
      hydroxysuccinimide ester of CBZ-protected L- or D-threonine with the central
      nitrogen. The effectiveness of each of these ligands in supporting the growth of
      Paracoccus denitrificans in a low-iron environment and the ability of these
      compounds to promote iron uptake are evaluated. The stereochemical configuration
      of the oxazoline ring is shown to be the major structural factor controlling both
      microbial growth stimulation and iron uptake. L-Fluviabactin, L-homofluviabactin,
      and L-agrobactin all promoted growth and iron uptake; D-fluviabactin was only
      marginally active. As with the microorganism's native siderophore, L-parabactin,
      all three ligands in the L-configuration investigated exhibited biphasic, i.e.,
      both high-affinity and low-affinity, kinetics. The high-affinity system (iron
      concentration < 1 microM) yielded K(m) values between 0.11 and 0.23 microM and
      V(max) values from 157 to 129 pg-atoms Fe min(-1) (mg of protein)(-1), whereas
      the low-affinity scheme (iron concentration > 1 microM) gave K(m) values from
      0.53 to 3.5 microM and V(max) values between 96 and 413 pg-atoms Fe min(-1) (mg
      of protein)(-1). Both L- and D-fluviabactin are very effective at clearing iron
      from the bile duct-cannulated rodent; when given subcutaneously at a dose of 150
      micromol/kg, both ligands had iron clearing efficiencies of >13%, which is much
      greater than that of desferrioxamine in this model. Thus, by altering the
      stereochemistry of certain microbial siderophores, it is possible to generate
      deferration agents that are still effective at clearing iron from animals, yet do
      not promote microbial growth.

PMID- 11448230
TI  - Bisubstrate ketone analogues as serotonin N-acetyltransferase inhibitors.
AB  - Serotonin N-acetyltransferase, also called the melatonin rhythm enzyme, is
      thought to play an important regulatory role in circadian rhythm in animals and
      people. A series of analogues were synthesized in which indole and coenzyme A
      were linked via ketone tethers as designed inhibitors of this enzyme. These
      compounds were tested against purified serotonin N-acetyltransferase. The parent
      ketone compound was found to be as potent as an amide linked compound studied
      previously, suggesting that there are no key hydrogen bonds to the nitrogen atom
      of the corresponding substrate necessary for tight inhibition. Reduction of the
      parent ketone afforded the diastereomeric carbinol mixture which showed reduced
      inhibitory potency, arguing against tetrahedral analogue mimicry as an important
      inhibitory theme. Several conformationally constrained ketone analogues were
      synthesized and investigated, and the results indicated that directing the
      orientation of the two substrates within the bisubstrate system could be used to
      maximize enzyme inhibition.

PMID- 11448231
TI  - Preparation and cytotoxicity toward cancer cells of mono(arylimino) derivatives
      of beta-lapachone.
AB  - A regio- and stereospecific synthesis of monoarylimino o-quinones derived from
      beta-lapachone (1) was achieved by treatment of the quinone with a slight excess
      of an arylamine in the presence of an excess of triethylamine/titanium
      tetrachloride 4:1. Imine formation occurred exclusively at position 6, giving the
      Z diastereomer, as determined by single-crystal X-ray analysis. In vitro tests
      for cytotoxicity in 55 human cancer cell cultures showed a substantial loss in
      activity for the p-nitrophenylimine (5), whereas the phenylimine (2), p
      methylphenylimine (3), and p-methoxyphenylimine (4) retained (or bettered) most
      of the cytotoxicity and selectivity of the parent quinone. Preliminary in vivo
      testing in hollow fiber assays against a standard panel of 12 human tumor cell
      lines showed that although beta-lapachone failed, compounds 2 and 3 had good
      scores with net cell kills.

PMID- 11448232
TI  - ElogD(oct): a tool for lipophilicity determination in drug discovery. 2. Basic
      and neutral compounds.
AB  - We present an RP-HPLC method for the determination of the octanol-water
      distribution coefficients at pH 7.4, as log values, for neutral and basic drugs,
      which combines ease of operation with high accuracy. The method is shown to work
      for a training set of 90 molecules comprised largely of drugs, and it was also
      applied to a test set of 10 proprietary compounds. This work expands the
      applicability of the method presented in our earlier report, for the
      determination of logP(oct) for neutral compounds (J. Med. Chem. 2000, 43, 2922
      2928), and it offers the same general features but widens the scope. Generally,
      the method (i) is compound sparing (< or =1 mL of a 50-100 microg/mL solution
      needed), (ii) is insensitive to concentration and phase ratio effects observed in
      some shake-flask determinations, (iii) is amenable to rapid determinations (< or
      = 20 min on average), (iv) is insensitive to impurities, (v) possesses a wide
      lipophilicity range (>7 log units), and (vi) offers a good accuracy, (vii) an
      excellent reproducibility, (viii) and an excellent potential for automation. To
      the best of our knowledge, a similar performance, on a set of noncongeneric
      drugs, has not been previously reported. We refer to the value generated via this
      method as ElogD(oct).

PMID- 11448233
TI  - Biological factors influencing the RBE of neutrons: implications for their past,
      present and future use in radiotherapy.
AB  - The recent resurgence of interest in fast-neutron therapy, particularly for the
      treatment of prostate cancer, warrants a review of the original radiobiological
      basis for this modality and the evolution of these concepts that resulted from
      subsequent experimentation with the fast-neutron beams used for randomized
      clinical trials. It is clear from current radiobiological knowledge that some of
      the postulates that formed the mechanistic basis for past clinical trials were
      incorrect. Such discrepancies, along with the inherent physical disadvantages of
      neutron beams in terms of collimation and intensity modulation, may partially
      account for the lack of therapeutic benefit observed in many randomized clinical
      trials. Moreover, it is equally apparent that indiscriminate prescription of fast
      neutron therapy is likely to lead to an adverse clinical outcome in a proportion
      of patients. Hence any renewed efforts to establish a niche for this modality in
      clinical radiation oncology will necessitate the development of a triage system
      that can discriminate those patients who might benefit from fast-neutron therapy
      from those who might be harmed by it. In the future, fast-neutron therapy might
      be prescribed based upon the relative status of appropriate molecular parameters
      that have a differential impact upon radiosensitivity to photons compared to fast
      neutrons.

PMID- 11448234
TI  - Mortality after cerebral angiography with or without radioactive Thorotrast: an
      international cohort of 3,143 two-year survivors.
AB  - There are few studies on the long-term sequelae of radionuclides ingested or
      injected into the human body. Patients exposed to radioactive Thorotrast in the
      1930s through the early 1950s provide a singular opportunity, since the
      administration of this radiographic contrast agent resulted in continuous
      exposure to alpha particles throughout life at a low dose rate. We evaluated
      cause-specific mortality among an international cohort of 3,143 patients injected
      during cerebral angiography with either Thorotrast (n = 1,736) or a similar but
      nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized
      mortality ratios (SMRs) for Thorotrast and comparison patients were calculated,
      and relative risks (RR), adjusted for population, age and sex, were obtained by
      multivariate statistical modeling. Most patients were followed until death, with
      only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the
      study. All-cause mortality (n = 1,599 deaths) was significantly elevated among
      Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly
      increased relative risks were found for several categories, including cancer (RR
      2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and
      benign liver disorders (RR 6.5). Nonsignificant increases were seen for
      respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The
      relative risk due to all causes increased steadily after angiography to reach a
      threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed
      for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P <
      0.05). Increasing cumulative dose of radiation was directly associated with death
      due to all causes combined, cancer, respiratory disease, benign liver disease,
      and other types of digestive disease. Our study confirms the relationship between
      Thorotrast and increased mortality due to cancer, benign liver disease, and
      benign hematological disease, and suggests a possible relationship with
      respiratory disorders and other types of digestive disease. The cumulative excess
      risk of cancer death remained high up to 50 years after injection with >20 ml
      Thorotrast and approached 50%.

PMID- 11448235
TI  - Sequence-specific damage induced by the impact of 3-30 eV electrons on
      oligonucleotides.
AB  - The ability of low-energy electrons to induce single- and double-strand breaks in
      DNA has recently been demonstrated. Here we show the propensity of 3-30 eV
      electrons to initiate base sequence-dependent damage to a short single DNA
      strand. Solid monolayer films of homogeneous thymidine (T(9)) and deoxycytidine
      (dCy(9)) and heterogeneous oligomers (T(6)dCy(3)) are bombarded with 1-30 eV
      electrons in an ultrahigh-vacuum system. CN, OCN and/or H(2)NCN are detected by a
      mass spectrometer as the most intense neutral fragments desorbing in vacuum. A
      weaker signal of CH(3)CCO is also detected, but only from oligonucleotides
      containing thymine. Below 17 eV, the energy dependence of the yields of CN, OCN
      and CH(3)CCO exhibits resonance-like structures, attributed to dissociative
      electron attachment (DEA). Above 17 eV, the monotonic increase in the fragment
      yields indicates that nonresonant processes (i.e. dipolar dissociation) control
      the fragmentation of these molecules. Within the energy range investigated,
      comparison of the magnitude of the total fragment yields produced by electron
      attack on dCy(9), T(6)-dCy(3) and T(9) suggests the following order in the
      sensitivity of single-strand DNA: dCy(9) > T(6)-dCy(3) > T(9). At 12 eV, the
      total fragment yields are found to be 5.8, 5.0 and 3.9 x 10(-3)
      fragment/electron, respectively. From the yields obtained with the two homo
      oligonucleotides, we differentiate between contributions arising from the
      chemical nature of the base and the effect of environment (i.e. the sequence)
      when a thymidine unit in T(9) is replaced by dCy. The base sequence-dependent
      damage is found to vary with incident electron energy. These results reinforce
      the idea that genomic sensitivity to ionizing radiation depends on local genetic
      information. Furthermore, they underscore the possible role of low-energy
      electrons in the pathways responsible for the induction of specific genomic
      lesions.

PMID- 11448236
TI  - Strand breaks in whole plasmid dna produced by the decay of (125)I in a triplex
      forming oligonucleotide.
AB  - DNA strand breaks produced by the decay of (125)I positioned against a specific
      site in plasmid DNA via a triplex-forming oligonucleotide were studied both in
      the immediate vicinity of the site of the decay with a single nucleotide
      resolution and in the whole plasmid by measuring the percentages of supercoiled,
      open-circular and linear forms. The localized breaks are distributed within 10 bp
      in each direction from the decay site with maxima in both strands just opposite
      the (125)I-dC residue in the triplex-forming oligonucleotide. The distributions
      of breaks in the two DNA strands are almost symmetrical, in agreement with the
      geometry of the pyrimidine motif triplex. We found that about 25% of the double
      strand breaks were located outside the 90-bp fragment containing the triplex
      forming oligonucleotide binding sequence. The ratio of single- to double-strand
      breaks in the whole plasmid was 11 for bound triplex-forming oligonucleotide
      compared to 26 when the triplex-forming oligonucleotide was free in solution. The
      number of double-strand breaks per decay of (125)I was 0.46 for bound triplex
      forming oligonucleotide and 0.17 for free triplex-forming oligonucleotide.
      Comparing the data on the localized damage and those for the whole plasmid, we
      concluded that, in addition to DNA breaks that are confined to a helical turn
      around the (125)I atom, the decay can produce breaks hundreds of base pairs away
      in the plasmid molecule. This linear plasmid molecule containing radiation
      induced damage at a specific DNA site should be useful in studies of the
      molecular mechanisms of DNA repair.

PMID- 11448237
TI  - Analysis of gene transcription in cells lacking DNA-PK activity.
AB  - The DNA-dependent protein kinase (DNA-PK), comprised of the Ku70/Ku80 (now known
      as G22p1/Xrcc5) heterodimer and the catalytic subunit DNA-PKcs (now known as
      Prkdc), is required for the nonhomologous end joining (NHEJ) pathway of DNA
      double-strand break repair. The mechanism of action of DNA-PK remains unclear. We
      have investigated whether DNA-PK regulates gene transcription in vivo after DNA
      damage using the subtractive hybridization technique of cDNA representational
      difference analysis (cDNA RDA). Differential transcription, both radiation
      dependent and independent, was detected and confirmed in primary mouse embryo
      fibroblasts from DNA-PKcs(-/-) and DNA-PKcs(+/+) mice. We present evidence that
      transcription of the extracellular matrix gene laminin alpha 4 (Lama4) is
      regulated by DNA-PK in a radiation-independent manner. However, screening of both
      primary and immortalized DNA-PKcs-deficient cell lines demonstrates that the
      majority of differences were not consistently dependent on DNA-PK status. Similar
      results were obtained in experiments using KU mutant hamster cell lines,
      indicating heterogeneity of transcription between closely related cell lines. Our
      results suggest that while DNA-PK may be involved in limited gene-specific
      transcription, it does not play a major role in the transcriptional response to
      DNA damage.

PMID- 11448238
TI  - Adaptive response and the bystander effect induced by radiation in C3H 10T(1/2)
      cells in culture.
AB  - This paper discusses two phenomena of importance at low doses that have an impact
      on the shape of the dose-response relationship. First, there is the bystander
      effect, the term used to describe the biological effects observed in cells that
      are not themselves traversed by a charged particle, but are neighbors of cells
      that are; this exaggerates the effect of small doses of radiation. Second, there
      is the adaptive response, whereby exposure to a low level of DNA stress renders
      cells resistant to a subsequent exposure; this reduces the effect of low doses of
      radiation. The present work was undertaken to assess the relative importance of
      the adaptive response and the bystander effect induced by radiation in C3H
      10T(1/2) cells in culture. When the single-cell microbeam delivered from 1 to 12
      alpha particles through the nuclei of 10% of C3H 10T(1/2) cells, more cells were
      inactivated than were actually traversed by alpha particles. The magnitude of
      this bystander effect increased with the number of particles per cell. An
      adaptive dose of 2 cGy of gamma rays, delivered 6 h beforehand, canceled out
      about half of the bystander effect produced by the alpha particles.

PMID- 11448239
TI  - Probing irradiated DNA with the perturbed angular correlation method.
AB  - The technique of perturbed angular correlations of gamma rays has been used to
      study the effects of radiation on DNA molecules. The samples are buffered
      solutions of calf thymus DNA exposed to various doses (0-80 Gy) of gamma rays.
      Indium-111 is used as a probe. Rotational correlation times, tau(c), a parameter
      measuring the flexibility of a macromolecule, are obtained that show a dependence
      on radiation dose.

PMID- 11448240
TI  - Genotoxic effects of high-energy iron particles in human lymphoblasts differing
      in radiation sensitivity.
AB  - The effects of (56)Fe particles and (137)Cs gamma radiation were compared in TK6
      and WTK1 human lymphoblasts, two related cell lines which differ in TP53 status
      and in the ability to rejoin DNA double-strand breaks. Both cell lines were more
      sensitive to the cytotoxic and clastogenic effects of (56)Fe particles than to
      those of gamma rays. However, the mutagenicity of (56)Fe particles and gamma rays
      at the TK locus was the same per unit dose and was higher for gamma rays than for
      (56)Fe particles at isotoxic doses. The respective RBEs for TK6 and WTK1 cells
      were 1.5 and 1.9 for cytotoxicity and 2.5 and 1.9 for clastogenicity, but only 1
      for mutagenicity. The results indicate that complex lesions induced by (56)Fe
      particles are repaired less efficiently than gamma-ray-induced lesions, leading
      to fewer colony-forming cells, a slightly higher proportion of aberrant cells at
      the first division, and a lower frequency of viable mutants at isotoxic doses.
      WTK1 cells (mutant TP53) were more resistant to the cytotoxic effects of both
      gamma rays and (56)Fe particles, but showed greater cytogenetic and mutagenic
      damage than TK6 cells (TP53(+)). A deficiency in the number of damaged TK6 cells
      (a) reaching the first mitosis after exposure and (b) forming viable mutants can
      explain these results.

PMID- 11448241
TI  - Rescue of lethally irradiated mice from hematopoietic death by pre-exposure to
      0.5 Gy X rays without recovery from peripheral blood cell depletion and its
      modification by OK432.
AB  - Exposing mice to 0.5 Gy X rays 2 weeks before lethal irradiation has been
      reported to induce marked radioresistance and to rescue them from hematopoietic
      death. Here we examined effects of the 0.5-Gy pre-exposure on hematological
      changes in C57BL mice that were lethally irradiated with 6.5 Gy X rays.
      Approximately 77% of pre-exposed mice survived 30 days after this irradiation,
      whereas 80% of mice that did not receive this pre-exposure died by day 20.
      However, regardless of the pre-exposure, peripheral blood cell counts decreased
      markedly by day 3 and reached a nadir at day 20. CFU-S in femur and CFU-GM in
      spleen had started to recover at day 10 and 14, respectively, but recovery of
      functional peripheral blood cells occurred later. The effect of pre-exposure on
      survival was altered by OK432, a bioresponse modifier; the effect depended on the
      timing of its administration. OK432 given 2 days before 0.5 Gy enhanced the
      protective effect of pre-exposure, resulting in the survival of 97% of the mice.
      In contrast, injection of OK432 1 day before or 2 days after pre-exposure led to
      100% mortality. Thus the survival-promoting effect of 0.5 Gy could be altered by
      OK432. The OK432-induced changes in the survival of mice could not be attributed
      solely to hematological changes, as shown by blood cell counts and progenitor
      cell contents. These results suggest that radioresistance induced by pre-exposure
      to 0.5 Gy X rays is not stable, but rather varies with the physiological
      conditions, and can be modulated by factors such as OK432.

PMID- 11448242
TI  - Redox metal chelation ameliorates radiation-induced bone marrow toxicity in a
      mouse model.
AB  - Since zinc desferrioxamine (Zn-DFO) has been shown to be a very potent protector
      against injuries induced by redox-active metal ions, we examined its protective
      effect against radiation-induced toxicity. We found that treatment with Zn-DFO
      given before TBI increased the survival of mice irradiated with 7.5 and 8.5 Gy.
      Zn-DFO also protected against radiation-induced myelosuppression and body weight
      loss, while soluble Il6 levels in serum were normalized in mice pretreated with
      Zn-DFO. We concluded that administration of Zn-DFO prior to TBI protected BALB/c
      mice from radiation-induced toxicity, increasing survival rates by up to 75%. The
      biological effect of Zn-DFO is known to result from its effect on the production
      of intracellular hydroxyl free radicals mediated by redox-active metal ions, and
      both metal chelation and zinc delivery appear to be equally likely mechanisms for
      this outcome. We suggest that radiation-induced toxicity is caused by the
      deleterious effect of redox-active metal ions, and that compounds which modulate
      this redox activity may act as radioprotectors.

PMID- 11448243
TI  - The Columbia University single-ion microbeam.
AB  - A single-ion microbeam facility has been constructed at the Columbia University
      Radiological Research Accelerator Facility. The system was designed to deliver
      defined numbers of helium or hydrogen ions produced by a van de Graaff
      accelerator, covering a range of LET from 30 to 220 keV/microm, into an area
      smaller than the nuclei of human cells growing in culture on thin plastic films.
      The beam is collimated by a pair of laser-drilled apertures that form the beam
      line exit. An integrated computer control program locates the cells and positions
      them for irradiation. We present details of the microbeam facility including
      descriptions of the collimators, hardware, control program, and the various
      protocols available. Various contributions to targeting and positioning precision
      are discussed along with our plans for future developments. Beam time for outside
      users is often available (see www.raraf.org).

PMID- 11448244
TI  - A novel double lesion in X-irradiated DNA consists of a strand break and a base
      modification.
AB  - A single free radical-initiating event can produce a pair of base lesions in DNA
      oligomers exposed to ionizing radiation. Whereas double base lesions have been
      observed previously, the present study shows that double lesions may sometimes
      consist of a base lesion and an associated strand break. The mechanism for the
      formation of double lesions is discussed. A redox process is postulated in which
      guanine is the source of the electron. It is suggested that double lesions may be
      formed in DNA either on adjacent nucleotides or, alternatively, on nucleotides
      separated by one, two or possibly more intervening nucleotides. It is
      hypothesized that intramolecular electron transfer facilitates the formation of
      double lesions on nonadjacent nucleotides.

PMID- 11448245
TI  - Adjustments to the baseline lung cancer mortality for radon-induced lung cancers
      in the BEIR VI risk models.

PMID- 11448246
TI  - Comments on "Chemoradiation for carcinoma of the cervix: advances and
      opportunities" by Patricia Eifel (Radiat. Res. 154, 229-236, 2000).

PMID- 11448248
TI  - Quality of care and service as perceived by adults with developmental
      disabilities, their parents, and primary caregivers.
AB  - How adults with developmental disabilities perceive quality of the care and
      service they receive was investigated and these perceptions compared with those
      of their parents and primary caregivers. The sample was 34 adults with
      developmental disabilities, one of their parents, and their primary caregiver,
      all from a small Swedish municipality. We adapted Quality From the Patient's
      Perspective by using simple words and fewer response choices. Results showed it
      was possible to assess how adults with developmental disabilities evaluated
      actual care and service conditions. Evaluations of the subjective importance
      ascribed to these conditions proved too difficult. A high degree of similarity
      was found in ratings of perceived reality of care and service conditions by the
      adults with developmental disabilities, their parents, and caregivers.

PMID- 11448249
TI  - Double-blind, placebo-controlled trial of clonidine in hyperactive children with
      mental retardation.
AB  - A 12-week, double-blind, randomized, placebo-controlled trial of oral clonidine
      in three fixed doses (4, 6, and 8 mcg/kg/day) using a crossover design was
      conducted with 10 children who had hyperkinetic disorder (mean age 7.6 years +/
      .54). All had comorbid mental retardation. Both parents' ratings on the Parent
      Symptom Questionnaire and clinicians' ratings on the Hillside Behaviour Rating
      Scale showed a marked dose-related response to clonidine in hyperactivity,
      impulsivity, and inattention. Drowsiness was a common side effect of clonidine.
      It wore off by the 2nd to 4th week in most cases. Thus, clonidine is a safe and
      effective medication in young hyperkinetic children with comorbid mental
      retardation.

PMID- 11448250
TI  - Perspectives of dentists, families, and case managers on dental care for
      individuals with developmental disabilities in Kansas.
AB  - The status of dental care for individuals with developmental disabilities in
      Kansas was examined. Dentists, family members, and case managers reported
      general, but partial, satisfaction with the availability, accessibility,
      appropriateness, and affordability of such care. Reasons for the results and
      recommendations for further improvement are discussed.

PMID- 11448251
TI  - Construction of adulthood and disability.
AB  - A discussion of adulthood in general and that of individuals with severe
      cognitive impairments was presented. The meaning of adulthood in our culture
      raises issues regarding the disparity between status as an adult and status as a
      person with a severe cognitive impairment. An examination of the traditional
      roles, rites, and rituals of adulthood (e.g., voting, marriage, consensual sex,
      and moving out of the family home) was provided. Personal deliberations on how
      the first author intends to assist her daughter in accessing these markers of
      adulthood are included. Our overall goal in this article is to promote discussion
      regarding adulthood and significant disabilities and to encourage additional
      movement toward full societal membership of adults with severe cognitive
      impairments.

PMID- 11448252
TI  - Employment, parenting, and well-being among mothers of children with
      disabilities.
AB  - The influence of employment on parenting stress among mothers of 5-year-old
      children with developmental disabilities and the influence of parenting demands
      (i.e., caregiving difficulty and behavior problems) and family support on their
      work quality and absenteeism from work was examined. No significant associations
      were found between employment status and parenting demands, family support, or
      stress for the sample as a whole. Among employed mothers, those who rated their
      jobs as interesting reported significantly less parenting stress when they
      experienced low or mean levels of parenting demands. Mothers' interest in work
      did not moderate the negative influence of high levels of parenting demands on
      stress. Finally, parenting demands increased absenteeism but had no effect on
      work quality. Implications of these findings are discussed.

PMID- 11448253
TI  - Beyond sex and cooking: health education for individuals with intellectual
      disability.
AB  - Issues of health education programming for people with intellectual disability
      are discussed. As environments in which such individuals live become more
      inclusive, and they are encouraged to make their own choices, the issue of
      whether current health education is sufficient to enable them to make healthy
      life choices is considered. More attention should be focused on programs in
      schools and the community to fulfill this need. Three aspects of health education
      programming are considered: physical activity, general health knowledge, and
      social supports for health. Continuity of information is viewed as important in
      policy development as well as in interprofessional coordination and cooperation
      to assure that these individuals are not further handicapped by poor health.

PMID- 11448254
TI  - Better managing the delivery of services and supports to people with
      developmental disabilities using information technology.

PMID- 11448255
TI  - A joint statement: Stop the execution of persons with mental retardation.

PMID- 11448261
TI  - Pathological gambling.

PMID- 11448262
TI  - Control "social carnivores" to prevent bites.

PMID- 11448263
TI  - Psychiatric symptoms common in neurological disorders.

PMID- 11448264
TI  - CAM Research attempts to separate wheat from chaff.

PMID- 11448270
TI  - Alcohol use as a prognostic factor following myocardial infarction.

PMID- 11448271
TI  - Alcohol use as a prognostic factor following myocardial infarction.

PMID- 11448272
TI  - Alcohol use as a prognostic factor following myocardial infarction.

PMID- 11448274
TI  - Pneumococcal vaccination in adults.

PMID- 11448276
TI  - Depth of excision of melanomas.

PMID- 11448278
TI  - Malignant hyperthermia and apparent heat stroke.

PMID- 11448279
TI  - Cigarette smoking as a risk factor for pancreatic cancer in patients with
      hereditary pancreatitis.

PMID- 11448280
TI  - Prevalence and predictive value of intermittent viremia with combination hiv
      therapy.
AB  - CONTEXT: In HIV-infected patients having virologic suppression (plasma HIV RNA
      <50 copies/mL) with antiretroviral therapy, intermittent episodes of low-level
      viremia have been correlated with slower decay rates of latently infected cells
      and increased levels of viral evolution, but the clinical significance of these
      episodes is unknown. OBJECTIVE: To determine if HIV-infected patients with
      intermittent viremia have a higher risk of virologic failure (confirmed HIV RNA
      >200 copies/mL). DESIGN AND SETTING: Retrospective analysis of subjects in well
      characterized cohorts, the AIDS Clinical Trials Group (ACTG) 343 trial of
      induction-maintenance therapy (August 1997 to November 1998) and the Merck 035
      trial (ongoing since March 1995). PATIENTS: Two hundred forty-one ACTG 343
      patients, of whom 101 received triple-drug therapy throughout the study, and a
      small group of 13 patients from Merck 035 having virologic suppression after 6
      months of indinavir-zidovudine-lamivudine. MAIN OUTCOME MEASURES: Association of
      intermittent viremia (plasma HIV RNA >50 copies/mL with a subsequent measure <50
      copies/mL) with virologic failure (2 consecutive plasma HIV RNA measures >200
      copies/mL) in both study groups; evidence of drug resistance in 7 patients from
      the small (n = 13) study group with long-term follow-up. RESULTS: Intermittent
      viremia occurred in 96 (40%) of the 241 ACTG 343 patients of whom 32 (13%) had 2
      consecutive HIV RNA values >50 copies/mL during the median 84 weeks of
      observation (median duration of observation after first intermittent viremia
      episode was 46 weeks). Of the 101 individuals receiving triple-drug therapy
      throughout, 29% had intermittent viremia; the proportion of episodes occurring
      during the maintenance period was 64% for the entire cohort and 68% for the group
      not receiving triple-drug therapy throughout vs 55% for those who did (P =.25).
      Intermittent viremia did not predict virologic failure: 10 (10.4%) of 96 patients
      with and 20 (13.8%) of 145 patients without intermittent viremia had virologic
      failure (relative risk, 0.76; 95% confidence interval [CI], 0.29-1.72). In a Cox
      proportional hazards model, the risk for virologic failure was not significantly
      greater in the ACTG 343 patients with intermittent viremia (hazard ratio, 1.28;
      95% CI, 0.59-2.79). Median viral load in 10 ACTG 343 patients assessed between 24
      and 60 weeks of therapy using an ultrasensitive 2.5-copies/mL detection level
      assay was 23 copies/mL in those with intermittent viremia vs <2.5 copies/mL in
      those without (P =.15). Intermittent viremia occurred in 6 of 13 patients from
      the small study group assessed after 76 to 260 weeks of therapy (using the 2.5
      copies/mL detection level assay) and was associated with a higher steady state of
      viral replication (P =.03), but not virologic failure over 4.5 years of
      observation. Viral DNA sequences from 7 patients did not show evolution of drug
      resistance. CONCLUSIONS: Intermittent viremia occurred frequently and was
      associated with higher levels of replication (Merck 035), but was not associated
      with virologic failure in patients receiving initial combination therapy of
      indinavir-zidovudine-lamivudine (ACTG 343 and Merck 035). In this population,
      treatment changes may not be necessary to maintain long-term virologic
      suppression with low-level or intermittent viremia.

PMID- 11448281
TI  - Validation of the Framingham coronary heart disease prediction scores: results of
      a multiple ethnic groups investigation.
AB  - CONTEXT: The Framingham Heart Study produced sex-specific coronary heart disease
      (CHD) prediction functions for assessing risk of developing incident CHD in a
      white middle-class population. Concern exists regarding whether these functions
      can be generalized to other populations. OBJECTIVE: To test the validity and
      transportability of the Framingham CHD prediction functions per a National Heart,
      Lung, and Blood Institute workshop organized for this purpose. DESIGN, SETTING,
      AND SUBJECTS: Sex-specific CHD functions were derived from Framingham data for
      prediction of coronary death and myocardial infarction. These functions were
      applied to 6 prospectively studied, ethnically diverse cohorts (n = 23 424),
      including whites, blacks, Native Americans, Japanese American men, and Hispanic
      men: the Atherosclerosis Risk in Communities Study (1987-1988), Physicians'
      Health Study (1982), Honolulu Heart Program (1980-1982), Puerto Rico Heart Health
      Program (1965-1968), Strong Heart Study (1989-1991), and Cardiovascular Health
      Study (1989-1990). MAIN OUTCOME MEASURES: The performance, or ability to
      accurately predict CHD risk, of the Framingham functions compared with the
      performance of risk functions developed specifically from the individual cohorts'
      data. Comparisons included evaluation of the equality of relative risks for
      standard CHD risk factors, discrimination, and calibration. RESULTS: For white
      men and women and for black men and women the Framingham functions performed
      reasonably well for prediction of CHD events within 5 years of follow-up. Among
      Japanese American and Hispanic men and Native American women, the Framingham
      functions systematically overestimated the risk of 5-year CHD events. After
      recalibration, taking into account different prevalences of risk factors and
      underlying rates of developing CHD, the Framingham functions worked well in these
      populations. CONCLUSIONS: The sex-specific Framingham CHD prediction functions
      perform well among whites and blacks in different settings and can be applied to
      other ethnic groups after recalibration for differing prevalences of risk factors
      and underlying rates of CHD events.

PMID- 11448282
TI  - The role of knee alignment in disease progression and functional decline in knee
      osteoarthritis.
AB  - CONTEXT: Knee osteoarthritis (OA) is a leading cause of disability in older
      persons. Few risk factors for disease progression or functional decline have been
      identified. Hip-knee-ankle alignment influences load distribution at the knee;
      varus and valgus alignment increase medial and lateral load, respectively.
      OBJECTIVE: To test the hypotheses that (1) varus alignment increases risk of
      medial knee OA progression during the subsequent 18 months, (2) valgus alignment
      increases risk of subsequent lateral knee OA progression, (3) greater severity of
      malalignment is associated with greater subsequent loss of joint space, and (4)
      greater burden of malalignment is associated with greater subsequent decline in
      physical function. DESIGN AND SETTING: Prospective longitudinal cohort study
      conducted March 1997 to March 2000 at an academic medical center in Chicago, Ill.
      PARTICIPANTS: A total of 237 persons recruited from the community with primary
      knee OA, defined by presence of definite tibiofemoral osteophytes and at least
      some difficulty with knee-requiring activity; 230 (97%) completed the study. MAIN
      OUTCOME MEASURES: Progression of OA, defined as a 1-grade increase in severity of
      joint space narrowing on semiflexed, fluoroscopically confirmed knee radiographs;
      change in narrowest joint space width; and change in physical function between
      baseline and 18 months, compared by knee alignment at baseline. RESULTS: Varus
      alignment at baseline was associated with a 4-fold increase in the odds of medial
      progression, adjusting for age, sex, and body mass index (adjusted odds ratio
      [OR], 4.09; 95% confidence interval [CI], 2.20-7.62). Valgus alignment at
      baseline was associated with a nearly 5-fold increase in the odds of lateral
      progression (adjusted OR, 4.89; 95% CI, 2.13-11.20). Severity of varus correlated
      with greater medial joint space loss during the subsequent 18 months (R = 0.52;
      95% CI, 0.40-0.62 in dominant knees), and severity of valgus correlated with
      greater subsequent lateral joint space loss (R = 0.35; 95% CI, 0.21-0.47 in
      dominant knees). Having alignment of more than 5 degrees (in either direction) in
      both knees at baseline was associated with significantly greater functional
      deterioration during the 18 months than having alignment of 5 degrees or less in
      both knees, after adjusting for age, sex, body mass index, and pain. CONCLUSION:
      This is, to our knowledge, the first demonstration that in primary knee OA varus
      alignment increases risk of medial OA progression, that valgus alignment
      increases risk of lateral OA progression, that burden of malalignment predicts
      decline in physical function, and that these effects can be detected after as
      little as 18 months of observation.

PMID- 11448283
TI  - HIV-1 drug resistance profiles in children and adults with viral load of <50
      copies/ml receiving combination therapy.
AB  - CONTEXT: The continued release of human immunodeficiency virus type 1 (HIV-1)
      into plasma at very low levels during highly active antiretroviral therapy
      (HAART) can be detected using specialized techniques, but the nature and
      significance of this low-level viremia, especially as related to acquisition of
      drug resistance mutations, are unclear. OBJECTIVE: To determine genetic
      resistance profiles of low-level plasma HIV-1 in patients with prolonged viral
      suppression (<50 copies/mL of plasma HIV-1 RNA) while receiving HAART. DESIGN AND
      SETTING: Cross-sectional study conducted at a US academic hospital from November
      1999 to February 2001 using a novel method for amplification of low levels of
      viral genomes in plasma. PATIENTS: Eighteen HIV-1-infected patients (7 children
      and 11 adults), enrolled in a longitudinal study of HIV-1 reservoirs, who had
      suppression of viral replication while receiving protease inhibitor-containing
      combination therapy. Two patients (1 adult and 1 child) with less optimal
      suppression of viral replication were included to assess virus predominating when
      plasma HIV-1 RNA levels are low but detectable (<1000 copies/mL). Follow-up
      analyses were conducted in 3 patients. MAIN OUTCOME MEASURE: Detection of drug
      resistance mutations in clones amplified from low-level plasma virus. RESULTS:
      Viral sequences were amplified from 8 of the 18 patients with simultaneous plasma
      HIV-1 measurements of less than 50 copies/mL and from 2 patients with 231 and 50
      copies/mL. Clones from 3 treatment-naive patients with less than 50 copies/mL of
      plasma HIV-1 RNA showed continued release, for as long as 42 months, of wild-type
      drug-sensitive virus. The 7 patients with prior nonsuppressive therapy, with
      viral loads below 50 copies/mL and during "blips" to 231 and 64 copies/mL, had
      only resistance mutations consistent with pre-HAART therapy (although reverse
      transcriptase inhibitor mutations may have continued to occur). New HAART-related
      mutations were seen in a control patient with prior viral load levels of about
      400 to 1000 copies/mL. For phylogenetic analysis, sequences were available for
      both resting CD4(+) T cells and plasma HIV for 7 of 10 patients and showed
      patient-specific clustering of sequences and a close relationship between virus
      in the plasma and the latent reservoir. CONCLUSIONS: Based on the samples that
      could be amplified, low-level viremia in children and adults receiving HAART with
      prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may
      result primarily from archival, pre-HAART virus, reflecting earlier treatment
      conditions, and does not appear to require development of new, HAART-selected
      mutations reflecting partial resistance to therapy. Low-level viremia below 50
      copies/mL may represent less of a concern regarding impending drug failure of
      current HAART regimens. However, the archival drug-resistant virus may be
      relevant regarding future treatment strategies.

PMID- 11448284
TI  - Herbal medicines and perioperative care.
AB  - CONTEXT: Widespread use of herbal medications among the presurgical population
      may have a negative impact on perioperative patient care. OBJECTIVES: To review
      the literature on commonly used herbal medications in the context of the
      perioperative period and provide rational strategies for managing their
      preoperative use. DATA SOURCES: The MEDLINE and Cochrane Collaboration databases
      were searched for articles published between January 1966 and December 2000 using
      the search terms herbal medicine, phytotherapy, and alternative medicine and the
      names of the 16 most commonly used herbal medications. Additional data sources
      were obtained from manual searches of recent journal articles and textbooks.
      STUDY SELECTION: We selected studies, case reports, and reviews addressing the
      safety and pharmacology of 8 commonly used herbal medications for which safety
      information pertinent to the perioperative period was available. DATA EXTRACTION:
      We extracted safety, pharmacodynamic, and pharmacokinetic information from the
      selected literature and reached consensus about any discrepancies. DATA
      SYNTHESIS: Echinacea, ephedra, garlic, ginkgo, ginseng, kava, St John's wort, and
      valerian are commonly used herbal medications that may pose a concern during the
      perioperative period. Complications can arise from these herbs' direct and
      pharmacodynamic or pharmacokinetic effects. Direct effects include bleeding from
      garlic, ginkgo, and ginseng; cardiovascular instability from ephedra; and
      hypoglycemia from ginseng. Pharmacodynamic herb-drug interactions include
      potentiation of the sedative effect of anesthetics by kava and valerian.
      Pharmacokinetic herb-drug interactions include increased metabolism of many drugs
      used in the perioperative period by St John's wort. CONCLUSIONS: During the
      preoperative evaluation, physicians should explicitly elicit and document a
      history of herbal medication use. Physicians should be familiar with the
      potential perioperative effects of the commonly used herbal medications to
      prevent, recognize, and treat potentially serious problems associated with their
      use and discontinuation.

PMID- 11448285
TI  - No-fault compensation for medical injuries: the prospect for error prevention.
AB  - Leading patient safety proposals promote the design and implementation of error
      prevention strategies that target systems used to deliver care and eschew
      individual blame. They also call for candor among practitioners about the causes
      and consequences of medical injury. Both goals collide with fundamental tenets of
      the medical malpractice system. Thus, the challenge of addressing error in
      medicine demands a thorough reconsideration of the legal mechanisms currently
      used to deal with harms in health care. In this article, we describe an
      alternative to litigation that does not predicate compensation on proof of
      practitioner fault, suggest how it might be operationalized, and argue that there
      is a pressing need to test its promise. We tackle traditional criticisms of "no
      fault" compensation systems for medical injury-specifically, concerns about their
      cost and the presumption that eliminating liability will dilute incentives to
      deliver high-quality care. Our recent empirical work suggests that a model
      designed around avoidable or preventable injuries, as opposed to negligent ones,
      would not exceed the costs of current malpractice systems in the United States.
      Implementation of such a model promises to promote quality by harmonizing injury
      compensation with patient safety objectives, especially if it is linked to
      reforms that make institutions, rather than individuals, primarily answerable for
      injuries.

PMID- 11448286
TI  - Durable HIV treatment benefit despite low-level viremia: reassessing definitions
      of success or failure.

PMID- 11448287
TI  - Principles, pragmatism, and medical injury.

PMID- 11448292
TI  - What is Kearns-Sayre syndrome after all?

PMID- 11448293
TI  - Establishing a standard of speed for assessing the efficacy of the
      serotonin(1B/1D) agonists (triptans).
AB  - The current International Headache Society guidelines for migraine clinical
      trials recommend assessment of pain relief at 2 hours as a primary end point.
      Patients, however, express a clear preference for more rapid pain relief, with
      most patients defining rapid relief as occurring within 30 minutes after drug
      administration. Thus, consideration should be given to establishing clinical
      trial end points that more accurately reflect the preferences of patients with
      migraine. In this case, assessment of pain relief at 1 hour would be an
      appropriate primary end point. Using speed of relief as a criterion for migraine
      drug selection also is appropriate. The migraine-specific serotonin(1B/1D)
      agonists, or triptans, are able to meet this faster relief end point and are
      preferred by patients.

PMID- 11448294
TI  - Optical imaging and its role in clinical neurology.

PMID- 11448295
TI  - Relationship between magnetic resonance arterial patency and perfusion-diffusion
      mismatch in acute ischemic stroke and its potential clinical use.
AB  - BACKGROUND: In patients with acute ischemic stroke the magnetic resonance (MR)
      perfusion-diffusion mismatch pattern (perfusion lesion at least 20% larger than
      the lesion on diffusion-weighted imaging) may indicate ischemically threatened
      but viable tissue. To our knowledge, the relationship of this MR pattern to
      serial changes in MR angiography (MRA) has not been reported. OBJECTIVES: To
      investigate the relationship between MRA changes and patterns of diffusion
      weighted imaging and perfusion abnormalities and to determine if the information
      obtained could be used in clinical management. METHODS: The MR studies of 35
      patients who had undergone sequential multimodality MR imaging studies within the
      first 4 days of stroke were reviewed. All lesions were in the internal carotid
      artery territory distribution. Magnetic resonance angiographies were read by 2
      observers blinded to the clinical data. RESULTS: During the first 24 hours a
      perfusion-diffusion mismatch was present in 22 (92%) of the 24 patients with an
      MRA arterial occlusive lesion. (At this time 5 [46%] of the 11 patients with a
      normal MRA [P =.006] also had a mismatch.) Two to 4 days after stroke, of these
      22 patients resolution of the mismatch occurred in 8 (87%) of 9 patients with
      recanalization on MRA compared with 5 (39%) of 13 patients without arterial
      recanalization (P =.03). Resolution of mismatch occurred in 3 (60%) of 5 patients
      with a normal MRA and a mismatch at the first time point. CONCLUSIONS:
      Concordance between MRA and the MR perfusion-diffusion mismatch pattern provides
      supportive evidence for an arterial vascular basis for this MR signature in acute
      stroke. Discordance between MRA lesions and mismatch may result from arterial
      branch occlusions undetected by MRA or from an alternate mechanism for the
      mismatch. The MR imaging patterns identified extend our understanding of the
      pathophysiology of stroke and may contribute to the improvement of stroke
      management in the future.

PMID- 11448296
TI  - Measurement of the midbrain diameter on routine magnetic resonance imaging: a
      simple and accurate method of differentiating between Parkinson disease and
      progressive supranuclear palsy.
AB  - Anteroposterior diameters of the suprapontine midbrain, the pons, and the
      collicular plate were measured in 50 patients with various parkinsonian syndromes
      (Parkinson disease [PD] [n = 20], progressive supranuclear palsy [PSP] [n = 16],
      and multiple-system atrophy of striatonigral type [n = 14]) and 12 age-matched
      healthy control subjects by means of axial T2-weighted magnetic resonance images.
      While no differences in midbrain diameter were found between patients with PD
      (mean, 18.5 mm) and control subjects (mean, 18.2 mm), patients with PSP had
      significantly lower midbrain diameters (mean, 13.4 mm) than patients with PD and
      control subjects (P<.001), without any overlap between these 2 groups. However,
      midbrain diameters of patients with multiple-system atrophy were also
      significantly lower than those of control subjects and patients with PD, with
      individual values showing overlap with the PSP, PD, and control groups. Pontine
      and collicular plate diameters did not contribute additional information. We
      therefore conclude that measurement of anteroposterior diameter of the midbrain
      on axial T2-weighted magnetic resonance images is a reliable means to
      differentiate patients with PSP from those with PD and should be incorporated
      into the diagnostic criteria for PSP.

PMID- 11448297
TI  - Treatment of depression is associated with suppression of nonspecific and antigen
      specific T(H)1 responses in multiple sclerosis.
AB  - OBJECTIVE: To examine the relationship between depression, treatment of
      depression, and interferon gamma (IFN-gamma) production by peripheral blood
      mononuclear cells in patients with comorbid diagnoses of relapsing-remitting
      multiple sclerosis (MS) and major depressive disorder. DESIGN: A randomized
      comparative outcome trial of three 16-week treatments for depression. Assessments
      were conducted at baseline, week 8, and treatment cessation. SETTING: An academic
      outpatient treatment and clinical research center. PATIENTS: Fourteen patients
      who met the criteria for relapsing-remitting MS and major depressive disorder.
      INTERVENTIONS: Individual cognitive behavioral therapy, group psychotherapy, or
      sertraline therapy. MAIN OUTCOME MEASURES: Depression was assessed using the Beck
      Depression Inventory. Interferon gamma production by peripheral blood mononuclear
      cells was measured following stimulation with OKT3 or recombinant human myelin
      oligodendrocyte glycoprotein (MOG). Variability in immune assays was controlled
      using 8 nondepressed healthy subjects who were enrolled at times corresponding
      with the enrollment of MS patients. RESULTS: Results of the Beck Depression
      Inventory were significantly related to IFN-gamma production stimulated with OKT3
      or MOG at baseline (P< or = .03 for all). Level of depression, OKT3-stimulated
      IFN-gamma production, and MOG-stimulated IFN-gamma production all declined
      significantly over the 16-week treatment period (P< or = .03 for all). Among
      controls, there were no significant changes over time in OKT3- or MOG-stimulated
      IFN-gamma, or in depression (P> or = .25 for all). CONCLUSIONS: These findings
      suggest that the production of the proinflammatory cytokine IFN-gamma by
      autoaggressive T cells in relapsing-remitting MS is related to depression and
      that treatment of depression may decrease IFN-gamma production. Thus, treatment
      of depression may provide a novel disease-modifying therapeutic strategy as well
      as a symptomatic treatment for patients with MS.

PMID- 11448298
TI  - Familial advanced sleep phase syndrome.
AB  - BACKGROUND: The circadian rhythms of sleep propensity and melatonin secretion are
      regulated by a central circadian clock, the suprachiasmatic nucleus of the
      hypothalamus. The most common types of sleep disorders attributed to an
      alteration of the circadian clock system are the sleep/wake cycle phase
      disorders, such as delayed sleep phase syndrome and advanced sleep phase syndrome
      (ASPS). Advanced sleep phase syndrome is characterized by the complaint of
      persistent early evening sleep onset and early morning awakening. Although the
      complaint of awakening earlier than desired is relatively common, particularly in
      older adults, extreme advance of sleep phase is rare. OBJECTIVE: To
      phenotypically characterize a familial case of ASPS. METHODS: We identified a
      large family with ASPS; 32 members of this family gave informed consent to
      participate in this study. Measures of sleep onset and offset, dim light
      melatonin onset, the Horne-Ostberg morningness-eveningness questionnaire, and
      clinical interviews were used to characterize family members as affected or
      unaffected with ASPS. RESULTS: Affected members rated themselves as "morning
      types" and had a significant advance in the phase of sleep onset (P<.001) and
      offset (P =.006) times. The mean sleep onset was 2121 hours for the affected
      family members and 0025 hours for the unaffected family members. The mean sleep
      offset was 0507 hours for the affected members and 0828 hours for the unaffected
      members. (Times are given in military form.) In addition, the phase of the
      circadian rhythm of melatonin onset for the affected family members was on
      average 3-1/2 hours earlier than for the unaffected members. CONCLUSIONS: The
      ASPS trait segregates with an autosomal dominant mode of inheritance. The
      occurrence of familial ASPS indicates that human circadian rhythms, similar to
      those in animals, are under genetic regulation. Genetic analysis of familial
      sleep and circadian rhythm disorders is important for identifying a specific
      gene(s) responsible for the regulation of sleep and circadian rhythms in humans.

PMID- 11448299
TI  - Mild Guillain-Barre syndrome.
AB  - BACKGROUND: The unpredictability of the early course of Guillain-Barre syndrome
      (GBS) makes it difficult to determine which patients' conditions will worsen
      under observation. Most large randomized treatment trials for GBS have used an
      inability to walk as the enrollment criterion. Consequently, little is known
      about the treatment of those patients with milder degrees of affection.
      OBJECTIVES: To determine the approximate frequency of mild GBS with the
      persistent ability to walk and to see if there were features that predicted that
      the illness would remain mild. SETTING: A registry of patients with GBS seen on
      the wards and in the neurology clinic from January 1,1992, to May 1, 2000, in a
      400-bed community teaching hospital. PATIENTS: Twelve (4.7%) of 254 patients in
      our case series were able to walk throughout their illness. Eight had been
      treated with plasmapheresis or intravenous immunoglobulin; the others were
      observed without treatment. RESULTS: There was no age, sex, or seasonal
      preponderance in comparison with large case series that included cases of all
      severities. Nine of 12 patients had a preceding respiratory tract infection, 10
      had paresthesias, 7 had prominent pain, and 9 had ataxia. Seven of 10 patients
      who were examined had normal cerebrospinal fluid protein levels. It took 8 days,
      on average, to reach the maximal degree of weakness. One additional treated
      patient, excluded from our case series, had mild weakness for the first 3 weeks
      and subsequently worsened with a relapsing course more typical of chronic
      inflammatory demyelinating polyneuropathy. Eleven patients demonstrated proximal,
      intermediate, or distal conduction block, and only 3 had a mild degree of
      denervation. There were no distinguishing clinical or electrophysiologic features
      between treated and untreated patients with mild GBS and, except for the mild
      degree of affection and the absence of substantial electromyographic changes of
      axonal disruption, there were no important differences between these mild cases
      as a group and patients who developed more severe GBS. CONCLUSIONS: Cases of mild
      GBS reach a clinical nadir in a similar time to those with more severe disease.
      Treatment may be unnecessary in patients who are able to walk during the second
      week of illness, but observation until approximately the eighth day seems
      appropriate to be certain that the illness does not progress. In all likelihood
      there are mild cases of GBS that never come to the attention of a neurologist.

PMID- 11448300
TI  - Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients
      and clinical and molecular characterization of spinocerebellar ataxia type 6.
AB  - BACKGROUND: Spinocerebellar ataxia (SCA) is a heterogeneous group of
      neurodegenerative disorders. The mutational basis for most of these disorders is
      an expanded CAG repeat sequence within the coding regions of the genes involved.
      The prevalence of SCA in the ethnic Chinese on Taiwan remains unclear. Moreover,
      there has been no report of SCA type 6 (SCA6) among Chinese people. OBJECTIVES:
      To characterize the prevalence of SCA in the ethnic Chinese on Taiwan, and to
      specifically characterize Chinese patients with SCA6 in terms of clinical and
      molecular features. PATIENTS AND METHODS: Using a molecular approach, we
      investigated SCA in 74 Taiwanese families with dominantly inherited ataxias and
      in 49 Taiwanese patients with sporadic ataxias. Clinical and molecular features
      of SCA6 were further characterized in 12 patients from 8 families and in 2
      sporadic cases. Furthermore, the intragenic polymorphic marker D19S1150 was
      amplified by polymerase chain reaction to analyze for linkage disequilibrium.
      RESULTS: Machado-Joseph disease-SCA3 was the most common type of autosomal
      dominant SCA in the Taiwanese cohort, accounting for 35 cases (47.3%), followed
      by SCA6 (8 [10.8%]), SCA2 (8 [10.8%]), SCA1 (4 [5.4%]), SCA7 (2 [2.7%]),
      dentatorubropallidoluysian atrophy (1 [1.4%]), and SCA8 (0%). The genes
      responsible for 16 (21.6%) of Taiwanese dominantly inherited SCA cases remain to
      be determined. Among the 49 patients with sporadic ataxias in the present series,
      2 (4.1%) were found to harbor SCA6 mutations. In the families with SCA6, we found
      significant anticipation in the absence of genetic instability on transmission,
      indicating that some other mechanism might account for the anticipation. The same
      frequent allele of the intragenic DNA marker (D19S1150) was shared by 7 of 10
      Taiwanese families with SCA6. CONCLUSIONS: Although SCA6 has, so far, not been
      reported in mainland Chinese, we found a geographic cluster of families with SCA6
      on Taiwan. Genotyping studies suggest a founder effect in the Taiwanese patients
      with SCA6.

PMID- 11448301
TI  - A new mitochondrial point mutation in the transfer RNA(Leu) gene in a patient
      with a clinical phenotype resembling Kearns-Sayre syndrome.
AB  - OBJECTIVE: To report on the molecular identification of a novel heteroplasmic G
      to-A transition at mitochondrial DNA position 3249 in transfer RNA(Leu) gene in a
      patient with a clinical phenotype resembling Kearns-Sayre syndrome. PATIENT AND
      METHODS: A 34-year-old patient had been suffering for more than 10 years from
      progressive visual failure, neurosensorial hearing loss, exercise intolerance,
      muscle weakness, paresthesia in the lower limbs, and difficulties swallowing.
      Clinical examination revealed generalized muscle wasting, ptosis, external
      ophthalmoplegia, and ataxia. Ophthalmologic examination showed dystrophic
      features in the cornea and retina. In skeletal muscle, morphologic and
      biochemical studies of the respiratory chain complexes were performed. Polymerase
      chain reaction, single-strand conformation polymorphism, and direct sequencing
      were used to screen for mutations in the 22 mitochondrial transfer RNA genes.
      RESULTS: In skeletal muscle, a significantly decreased catalytic activity of
      complex I was detected by spectrophotometric analysis and numerous cytochrome c
      oxidase-negative ragged-red fibers were seen on morphologic examination. A G-to-A
      substitution 3249 (G3249A) mutation was found in the transfer RNA(Leu) gene of
      the patient and mutant mitochondrial DNA represented 85% of the total in skeletal
      muscle but only 45% in leukocytes. The mutation was shown to be present in a
      small fraction in leukocytes from the unaffected mother and to be absent in
      leukocytes from the healthy sister. CONCLUSIONS: A causal relationship between a
      heteroplasmic G3249A transfer RNA(Leu) mutation in a patient suffering from
      progressive external ophthalmoplegia, retinal dystrophy, ataxia, neurosensorial
      hearing loss, and muscle wasting is postulated. To our knowledge, the G3249A
      mutation has never previously been described and was not detected in control
      subjects.

PMID- 11448302
TI  - Focal limb dystonia in a patient with a cerebellar mass.
AB  - BACKGROUND: Focal dystonia of acute onset is indicative of a structural lesion in
      the nervous system. Cerebellar lesions have rarely been associated with dystonia.
      CASE DESCRIPTION: A 42-year-old woman was admitted to the neurology ward because
      of fever, confusion, and gait unsteadiness. She was diagnosed as having
      tuberculous meningitis, and, after a few days of antituberculous treatment, she
      developed prominent dystonia of the left upper limb. Cranial nuclear magnetic
      resonance imaging showed an isolated lesion compatible with a tuberculoma in the
      left cerebellar hemisphere. Both the limb dystonia and the tuberculoma resolved
      with maintained antituberculous treatment. CONCLUSIONS: In the patient described,
      the presence of upper-limb dystonia ipsilateral to a focal cerebellar lesion and
      the resolution of the dystonia and the mass lesion following treatment suggest
      that the cerebellum or its connections to the thalamus and/or basal ganglia could
      be involved in the pathophysiology of the dystonia.

PMID- 11448303
TI  - Ballistic-choreic movements as the presenting feature of renal cancer.
AB  - BACKGROUND: The paraneoplastic syndromes can involve multiple areas of the
      central nervous system and result in a variety of neurological symptoms. To our
      knowledge, severe, rapidly progressive, and drug-resistant ballistic-choreic
      movements have not been previously described as the presenting feature of renal
      cell carcinoma. PATIENT AND METHODS: A previously healthy 55-year-old man
      developed limb ballismus and involuntary choreic movements of his face over
      several weeks. Extensive laboratory, diagnostic, and radiographic studies failed
      to reveal a cause, until an abnormality on a chest x-ray film prompted a search
      for a primary neoplasm and a final diagnosis of renal cell carcinoma. High doses
      of medications traditionally used to treat choreic disorders had no effect on the
      abnormal movements. A biopsy specimen of the basal ganglia showed focal
      encephalitic changes but no malignant neoplasm. CONCLUSIONS: Whereas prior cases
      of paraneoplastic syndromes with chorea have been reported in other forms of
      cancer, our case was significant because, to our knowledge, renal cell carcinoma
      has not been previously reported in association with this syndrome. Furthermore,
      the chorea was categorically resistant to pharmacological treatment, and the
      movement disorder was the initial and only focal neurological feature of the
      primary illness.

PMID- 11448304
TI  - Long-term effects of bilateral frontal brain lesion: 60 years after injury with
      an iron bar.
AB  - BACKGROUND: Harlow's report of the case of Phineas P. Gage in 1848 was one of the
      earliest description of the personality and behavioral changes following frontal
      lobe damage. Since Harlow's articles, a few more case reports of frontal lobe
      damage have been published. As standard neuropsychological and neurologic
      evaluations may reveal subtle defects, case reports have been particularly useful
      in characterizing the behavioral changes that follow frontal lobe damage.
      OBJECTIVE: To describe the long-term outcome of an 81-year-old patient who
      sustained a severe frontal brain lesion 60 years ago caused by the passage of an
      iron spike through his head. RESULTS: The patient has bilateral damage affecting
      the orbital and dorsolateral frontal regions. He displays many of the typical
      frontal behavioral disturbances described in the literature. His conduct is
      characterized by dependence on others, cheerfulness, planning difficulties,
      problems establishing realistic goals, lack of drive, and difficulties in
      initiating, continuing, and finishing activities. Although gross cognitive
      functioning is intact, neuropsychological deficits are present in the executive
      functioning, memory, and visuoconstructive domains. CONCLUSIONS: In contrast with
      the antisocial conduct pattern usually associated with frontal damage in the
      literature, this case suggests that large frontal lesions can produce behavioral
      and personality changes that are compatible with stable functioning in family,
      professional, and social settings. In addition to the localization of the lesion,
      many other factors should be considered in the long-term prognosis of frontal
      brain injured patients.

PMID- 11448305
TI  - Pituitary apoplexy.

PMID- 11448306
TI  - Acute spontaneous spinal epidural hematoma.

PMID- 11448307
TI  - Nineteenth-century contributions to the mechanical recording of postural sway.
AB  - In the first half of the 19th century, European physicians, including Marshall
      Hall, Bernardus Brach, and Moritz Romberg, described loss of postural control in
      darkness by patients with severely compromised proprioception. Late 19th-century
      neurologists developed instruments to measure and record postural sway in
      patients with neurologic disease. Principal American contributors were the
      neurologist Silas Weir Mitchell from Philadelphia, Pa, and his trainees Morris
      Lewis and Guy Hinsdale. The efforts of these neurologists anticipated later
      physiologic studies and ultimately the development of computerized dynamic
      platform posturography.

PMID- 11448308
TI  - Prosper Meniere and his disease.
AB  - In 1861, Prosper Meniere presented a paper before the French Academy of Medicine
      in which he described a series of patients with episodic vertigo and hearing
      loss. He also mentioned the postmortem examination of a young girl who
      experienced vertigo after a hemorrhage into the inner ear. Prior to that time,
      vertigo was thought to be a cerebral symptom similar to epileptic seizures.
      Meniere pointed out that vertigo frequently had a benign course and that common
      treatments, such as bleeding, often did more harm than good. He was not
      attempting to define a disease or syndrome but rather to emphasize that vertigo
      could originate from damage to the inner ear. Confusion regarding the clinical
      and pathologic features of Meniere disease persisted well into the 20th century.

PMID- 11448309
TI  - Jean-Baptiste Bouillaud, Claude-Francois Lallemand, and the role of the frontal
      lobe: location and mislocation of language in the early 19th century.
AB  - In 1825, Jean-Baptiste Bouillaud read a paper at the Royal Academy of Medicine in
      Paris supporting Franz Gall's theory of a relation between speech and the frontal
      lobes. Bouillaud argued that if the frontal lobes are crucial to speech, 2
      conditions must be satisfied: when the frontal lobes are affected, speech must
      also be affected; conversely, when the frontal lobes are spared, speech is also
      spared. Following these principles, he tested and argued in support of Gall's
      theory by analyzing the data from 2 neuropathological casebooks (Lallemand, 1820
      1823; Rostan, 1820 and 1823). We now know that Bouillaud was wrong, since the
      crucial dichotomy is between the left and right hemispheres and not between the
      anterior and posterior areas. What is interesting is that the actual data refute
      Bouillaud's conclusion. We replicated his experiment by reanalyzing the 147
      clinical cases described by Lallemand. There were, of course, some cases with
      frontal lesions and speech disorders; other cases, however, had speech disorders
      with lesions outside the frontal lobes, and still others had frontal lesions
      without speech disorders. Although Bouillaud did not notice it, as we expected,
      almost all patients with speech disorders had a left hemisphere lesion.

PMID- 11448310
TI  - Lesion of the basal ganglia and surgery for Parkinson disease.

PMID- 11448312
TI  - Report on statins and dementia disputed.

PMID- 11448314
TI  - Cytokines and seizures.

PMID- 11448316
TI  - Statins and dementia.

PMID- 11448318
TI  - The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, II:
      characteristics of patients enrolled and not enrolled. COMS Report No. 17.
AB  - OBJECTIVES: To describe characteristics of patients evaluated for the
      Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine
      125 brachytherapy for choroidal melanoma by enrollment status, and to compare
      characteristics of patients enrolled with those of patients with tumors of
      eligible size who did not enroll in order to assess the extent to which findings
      from the clinical trial can be generalized to future patients. METHODS: For all
      patients diagnosed with choroidal melanoma and evaluated for the clinical trial
      at COMS centers from November 1986 through July 31, 1998, selected data were
      transmitted to the COMS Coordinating Center, Baltimore, Md, where they were
      integrated and analyzed. Data included ophthalmic and medical history,
      examination findings, and visual acuity measurements recorded prior to
      enrollment; standardized A- and B-scan echographic examination findings; and wide
      angle fundus photographs and fluorescein angiograms. RESULTS: Of 8712 patients
      with choroidal melanoma, 5046 had tumors of eligible size; of these, 2882 (57%)
      were eligible for enrollment, and 1317 (46% of eligible patients, 26% of patients
      with tumors of eligible size) enrolled. Most differences between eligible and
      ineligible patients corresponded to eligibility and exclusion criteria. However,
      ineligible patients were older and had thicker tumors than eligible patients.
      Eligible patients who enrolled were slightly older and had larger tumors than
      those who did not enroll. Nearly half (48%) of enrolled patients had choroidal
      melanoma with the apex located temporal to the fovea, compared with 40% of
      eligible patients not enrolled and 29% of ineligible patients. CONCLUSIONS: This
      trial was designed to yield internally valid treatment comparisons through random
      assignment to treatment at time of enrollment. Information from this and other
      studies document that enrolled patients were similar to other patients with
      choroidal melanoma who were treated with 125I brachytherapy. These findings
      support the external validity of the trial and applicability of treatment
      findings to all patients who meet the criteria used to judge eligibility for the
      trial.

PMID- 11448319
TI  - The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma,
      III: initial mortality findings. COMS Report No. 18.
AB  - OBJECTIVES: To report initial mortality findings from the Collaborative Ocular
      Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs
      enucleation for treatment of choroidal melanoma. METHODS: Patients were evaluated
      for eligibility at 43 participating clinical centers in the United States and
      Canada. Eligible consenting patients were assigned randomly at the time of
      enrollment to enucleation or 125I brachytherapy. Patients were examined at
      specified intervals after enrollment for data collection purposes. Findings
      presented herein are based on data received by September 30, 2000. Data for each
      patient were analyzed with the treatment group to which the patient was assigned
      randomly at the time of enrollment. RESULTS: During the 11(1/2)-year accrual
      period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657
      to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have
      been misdiagnosed when histopathology was reviewed centrally. All but 17 patients
      (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol
      was excellent, with 91% of patients treated per protocol. Based on time since
      enrollment, 1072 patients (81%) had been followed for mortality for 5 years and
      416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660
      patients in the enucleation arm and 176 (27%) of 657 patients in the
      brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and
      82%, respectively; there was no clinically or statistically significant
      difference in survival rates overall (P =.48, log-rank test). The adjusted
      estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95%
      confidence interval [CI], 0.80-1.22). Five-year rates of death with
      histopathologically confirmed melanoma metastasis were 11% and 9% following
      enucleation and brachytherapy, respectively; after adjustment, the estimated risk
      ratio was 0.91 (95% CI, 0.66-1.24). CONCLUSIONS: Mortality rates following 125I
      brachytherapy did not differ from mortality rates following enucleation for up to
      12 years after treatment of patients with choroidal melanoma who enrolled in this
      COMS trial. The power of the study was sufficient to indicate that neither
      treatment is likely to increase or decrease mortality rates by as much as 25%
      relative to the other.

PMID- 11448320
TI  - Discriminating between normal and glaucomatous eyes using the Heidelberg Retina
      Tomograph, GDx Nerve Fiber Analyzer, and Optical Coherence Tomograph.
AB  - OBJECTIVE: To compare the ability of 3 instruments, the Heidelberg Retina
      Tomograph (HRT), the GDx Nerve Fiber Analyzer (GDx), and the Optical Coherence
      Tomograph (OCT), to discriminate between healthy eyes and eyes with early to
      moderate glaucomatous visual field loss. SUBJECTS AND METHODS: Forty-one patients
      with early to moderate glaucomatous visual field loss and 50 healthy subjects
      were included in the study. The HRT, GDx, and OCT imaging and visual field
      testing were completed on 1 eye from each subject within a 6-month interval.
      Statistical differences in sensitivity at fixed specificities of 85%, 90%, and
      95% were evaluated. In addition, areas under the receiver operating
      characteristic (ROC) curve were compared. RESULTS: No significant differences
      were found between the area under the ROC curve and the best parameter from each
      instrument: OCT thickness at the 5-o'clock inferior temporal position (mean +/-
      SE, 0.87 +/- 0.04), HRT mean height contour in the nasal inferior region (mean +/
      SE, 0.86 +/- 0.04), and GDx linear discriminant function (mean +/- SE, 0.84 +/-
      0.04). Twelve HRT, 2 GDx, and 9 OCT parameters had an area under the ROC curve of
      at least 0.81. At a fixed specificity of 90%, significant differences were found
      between the sensitivity of OCT thickness at the 5-o'clock inferior temporal
      position (71%) and parameters with sensitivities less than 52%. Qualitative
      assessment of stereophotographs resulted in a sensitivity of 80%. CONCLUSION:
      Although the area under the ROC curves was similar among the best parameters from
      each instrument, qualitative assessment of stereophotographs and measurements
      from the OCT and HRT generally had higher sensitivities than measurements from
      the GDx.

PMID- 11448321
TI  - Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing,
      efficacy, and safety evaluation of a novel compound for glaucoma management.
AB  - OBJECTIVE: To compare the safety and efficacy of the ocular hypotensive lipid AGN
      192024 (Lumigan) with those of timolol. METHODS: A 30-day, randomized,
      investigator-masked, clinical trial involving 100 patients with elevated
      intraocular pressure (IOP). Study medications were instilled topically. Doses of
      0.003%, 0.01%, or 0.03% AGN 192024 were given once daily for 3 weeks then twice
      daily for 1 week, and vehicle control or 0.5% timolol was given twice daily for 4
      weeks. Mean change in IOP from baseline was the primary efficacy variable. Safety
      parameters included adverse events, hyperemia grading, laser flare meter
      analysis, heart rate, and blood pressure. RESULTS: Timolol and all 3
      concentrations of AGN 192024 lowered IOP from baseline (P < .001). A dosage of
      0.03% AGN 192024 once daily lowered IOP significantly more than timolol (P < or =
      .02) at every study visit except day 21 (P = .053) and provided better diurnal
      IOP control. Twice-daily dosing of AGN 192024 provided no clinically significant
      benefit over once-daily dosing. All treatment regimens were safe and well
      tolerated, with no clinically significant effects on heart rate or blood pressure
      and no between-group differences in the incidence of adverse events. The only
      significant ocular safety finding with AGN 192024 was a dose-related mild
      increase in conjunctival hyperemia. CONCLUSIONS: Of the 3 concentrations tested,
      0.03% AGN 192024 once daily had the best therapeutic profile. AGN 192024 was safe
      and well tolerated, and it provided superior ocular hypotensive efficacy and
      diurnal IOP control compared with timolol in patients with ocular hypertension
      and glaucoma.

PMID- 11448322
TI  - Risk factors for late-onset infection following glaucoma filtration surgery.
AB  - OBJECTIVE: To determine the risk factors for late-onset infection following
      glaucoma filtration surgery. METHODS: We performed a case-control study comparing
      131 cases of late-onset infection collected from 27 surgeons at 10 centers with
      500 controls matched for date of surgery and surgeon. The criterion for the
      presence of infection was severe anterior chamber reaction occurring later than 4
      weeks after surgery. An opaque bleb and positive culture results were not
      required for diagnosis. Risk factors were identified by univariate and
      multivariate logistic regression analyses. RESULTS: Some of the risk factors that
      were statistically significant in the multivariate model after adjusting for age,
      race, and sex were (1) performance of a full-thickness rather than a guarded
      procedure (risk ratio [RR], 13.1; 95% confidence interval [CI], 2.12-80.9), (2)
      filtration surgery performed without concurrent cataract surgery (RR, 2.25; 95%
      CI, 1.24-4.08), (3) use of mitomycin (RR, 2.48; 95% CI, 1.06-5.83), (4)
      intermittent use of antibiotics after surgery (RR, 2.10; 95% CI, 1.09-4.02), and
      (5) continuous use of antibiotics after surgery (RR, 5.94; 95% CI, 2.09-16.9).
      CONCLUSIONS: Eyes undergoing full-thickness procedures or filtration surgery
      without cataract extraction are at increased risk for late infection.
      Intraoperative mitomycin and episodic or continuous antibiotic use after the
      postoperative period are associated with an increased risk of infection.

PMID- 11448323
TI  - Long-term nutrient intake and early age-related nuclear lens opacities.
AB  - OBJECTIVE: To assess the relation between usual nutrient intake and subsequently
      diagnosed age-related nuclear lens opacities. SUBJECTS: Four hundred seventy
      eight nondiabetic women aged 53 to 73 years from the Boston, Mass, area without
      previously diagnosed cataracts sampled from the Nurses' Health Study cohort.
      METHODS: Usual nutrient intake was calculated as the average intake from 5 food
      frequency questionnaires that were collected during a 13- to 15-year period
      before the evaluation of lens opacities. The duration of vitamin supplement use
      was determined from 7 questionnaires collected during this same period. We
      defined nuclear opacities as a nuclear opalescence grade of 2.5 or higher using
      the Lens Opacification Classification System III. RESULTS: The prevalence of
      nuclear opacification was significantly lower in the highest nutrient intake
      quintile category relative to the lowest quintile category for vitamin C
      (P<.001), vitamin E (P =.02), riboflavin (P =.005), folate (P =.009), beta
      carotene (P =.04), and lutein/zeaxanthin (P =.03). After adjustment for other
      nutrients, only vitamin C intake remained significantly associated (P =.003 for
      trend) with the prevalence of nuclear opacities. The prevalence of nuclear
      opacities was significantly lower (P<.001) in the highest vitamin C intake
      quintile category relative to the lowest quintile category (odds ratio, 0.31; 95%
      confidence interval, 0.16-0.58). There were also statistically significant trends
      of decreasing prevalence of nuclear opacities with increasing duration of use of
      vitamin C (P =.004 for trend), vitamin E (P =.03 for trend), and multivitamin (P
      =.04 for trend) supplements, but only duration of vitamin C supplement use
      remained significantly associated with nuclear opacities after mutual adjustment
      for use of vitamin E (P =.05 for trend) or multivitamin (P =.02 for trend)
      supplements. The prevalence of nuclear opacities was significantly lower (P
      =.004) for women who used a vitamin C supplement for 10 or more years relative to
      women who never used vitamin C supplements (odds ratio, 0.36; 95% confidence
      interval, 0.18-0.72). Plasma measures of vitamins C and E taken at the eye
      examination were also inversely associated with the prevalence of nuclear
      opacities. CONCLUSION: These results provide additional evidence that antioxidant
      nutrients play a role in the prevention of age-related nuclear lens opacities.

PMID- 11448324
TI  - Unilateral or asymmetric pseudoexfoliation syndrome? An ultrastructural study.
AB  - BACKGROUND: Clinically, most patients with pseudoexfoliation (PEX) syndrome
      reveal only unilateral ocular involvement. However, the generalized nature of the
      disorder suggests that PEX syndrome is clinically asymmetric rather than strictly
      unilateral. OBJECTIVE: To perform an ultrastructural study of the contralateral
      eyes in patients with unilateral PEX syndrome. METHODS: Five pairs of donor eyes
      with slitlamp microscopic, macroscopic, and light microscopic evidence of
      unilateral PEX syndrome and 6 normal control eyes were investigated by
      transmission electron microscopy and light and electron microscopic
      immunohistochemistry using antibodies against the human natural killer (HNK-1)
      epitope and against latent transforming growth factor beta1-binding protein, both
      markers for the identification of PEX deposits. RESULTS: Ultrastructural
      alterations were observed in anterior segment tissues of all apparently not
      involved fellow eyes. These included (1) deposits of typical PEX fibrils on the
      iris and ciliary epithelia and in the dilator muscle of the iris; (2) increased
      accumulation of extracellular matrix, including microfibrils and reduplicated
      basement membrane material in the periphery of iris vessels, in the dilator
      muscle and in the juxtacanalicular tissue of the trabecular meshwork; and (3)
      degenerative changes of the iris pigment epithelium and dilator muscle cells.
      Latent transforming growth factor beta1-binding protein- and HNK-1-positive
      deposits indicating PEX material accumulations were detected in the periphery of
      iris vessels and in the dilator muscle in all affected and contralateral eyes,
      but not in the control eyes. CONCLUSIONS: These subclinical alterations of
      contralateral eyes in clinically so-called unilateral PEX syndrome support the
      concept that PEX syndrome is a generalized basically bilateral disorder with a
      clinically marked asymmetric manifestation. The iris changes may account for the
      clinical signs characteristic of early stages, such as melanin dispersion,
      peripupillary atrophy, trabecular meshwork pigmentation, and insufficient
      asymmetric mydriasis. The findings should be considered in the clinical
      management of the patients. CLINICAL RELEVANCE: In view of the fact that PEX
      syndrome is the most common identifiable cause of open-angle glaucoma worldwide
      and as it is an important risk factor for a wide spectrum of ocular
      complications, particularly during cataract surgery, the potential involvement of
      both eyes in the PEX process is of clinical significance.

PMID- 11448325
TI  - Combined effect of cyclosporine and sirolimus on improving the longevity of
      recombinant adenovirus-mediated transgene expression in the retina.
AB  - OBJECTIVES: To reevaluate the longevity and intraocular safety of recombinant
      adenovirus (rAd)-mediated gene delivery after subretinal injection, and to
      prolong transgene expression through the combination of 2 synergistic
      immunosuppressants. METHODS: An rAd vector carrying green fluorescent protein
      (GFP) gene was delivered subretinally in the rat eye. The GFP expression was
      monitored in real time by fundus fluorescent photography. Intraocular safety was
      examined by observation of changes of retinal pigmentation, cell infiltration in
      virus-contacted area, immunophenotyping for CD4(+) and CD8(+) cytotoxic T
      lymphocytes, and CD68(+) macrophages, histologic findings, and dark-adapted
      electroretinography. Two synergistic immunosuppressants, cyclosporine and
      sirolimus, were used alone or in combination to prolong transgene expression by
      temporary immunosuppression. RESULTS: The GFP expression peaked on day 4,
      dramatically decreased on day 10, and was not detectable on day 14. The decreased
      GFP expression was coincident with cell infiltration in virus-contacted area.
      Immunostaining showed that the infiltrating cells were CD4(+) and CD8(+)
      cytotoxic T lymphocytes and CD68(+) macrophages. Clumped retinal pigmentation and
      decreased b wave of dark-adapted electroretinogram were observed at 3 to 4 weeks
      after injection. Histologic examination confirmed rAd-induced retinal
      degeneration. Transient immunosuppression by cyclosporine and sirolimus, either
      alone or in combination, improved transgene expression, with the combination
      being the most efficient. The combined immunosuppression attenuated but did not
      retard the rAd-induced retinal damage. CONCLUSIONS: Transgene expression mediated
      by rAd after subretinal delivery is short-term and toxic to the retina.
      Combination of cyclosporine and sirolimus may act as an immunosuppressive adjunct
      to prolong rAd-mediated gene transfer. CLINICAL RELEVANCE: The intraocular safety
      of rAd should be carefully considered before clinical trials are performed.

PMID- 11448326
TI  - Evidence for antigen-specific immune deviation in patients with acute retinal
      necrosis.
AB  - BACKGROUND: Because experimental acute retinal necrosis (ARN) induced by herpes
      simplex virus in mice develops only if mice fail to acquire virus-specific
      delayed hypersensitivity (DH), although they produce antiviral antibodies (ie,
      anterior chamber-associated immune deviation), we sought to determine whether a
      similar inverse correlation exists for patients with varicella-zoster virus (VZV)
      induced ARN. DESIGN: Patients with acute, VZV-induced ARN and age-matched control
      subjects were skin tested with VZV and purified protein derivative antigens to
      evaluate DH. Varicella-zoster virus-induced ARN was diagnosed using polymerase
      chain reaction and intraocular antibody quotient. Serum samples were collected
      and analyzed for anti-VZV and anti-herpes simplex virus antibody titers. Acute
      retinal necrosis activity was assessed clinically, and DH skin tests were
      repeated 3 months after onset when ocular recovery had taken place. RESULTS:
      Whereas controls displayed intense DH when tested with VZV and purified protein
      derivative antigens, a subset of patients with ARN displayed absent VZV-specific
      DH (although their purified protein derivative responses were normal). Patients
      with the most severe ARN had the lowest DH responses to VZV antigens. Serum anti
      VZV antibody titers were higher in patients with ARN than in controls, and
      antiviral titer correlated inversely with the intensity of anti-VZV DH responses.
      Varicella-zoster virus-specific DH responses were restored in patients who
      recovered from ARN. CONCLUSION: Varicella-zoster virus-ARN develops in a setting
      where DH reactivity to viral antigens is absent, implying that virus-specific DH
      might ameliorate the severity of ARN. CLINICAL RELEVANCE: Linking virus-specific
      DH to vulnerability to ARN in individuals infected with VZV might reveal an
      underappreciated pathogenic mechanism.

PMID- 11448327
TI  - Development of the 25-item National Eye Institute Visual Function Questionnaire.
AB  - OBJECTIVE: To develop and test the psychometric properties of a 25-item version
      of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). DESIGN:
      Prospective observational cohort study of persons with 1 of 5 chronic eye
      diseases or low vision who were scheduled for nonurgent visits in ophthalmology
      practices and a reference sample of persons without eye disease. SETTING: Eleven
      university-based ophthalmology practices and the NEI Clinical Center. PATIENTS:
      Eligible participants had to have 1 of the following eye conditions: age-related
      cataracts, age-related macular degeneration, diabetic retinopathy, primary open
      angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. Seven of
      the 12 sites also enrolled persons in a reference sample. Reference sample
      participants had no evidence of underlying eye disease but were scheduled for
      either screening eye examinations or correction of refractive error. All eligible
      persons had to be 21 years or older, English speaking, and cognitively able to
      give informed consent and participate in a health status interview. MEASUREMENTS
      AND MAIN RESULTS: To provide the data needed to create the NEI VFQ-25, all
      subjects completed an interview that included the 51-item NEI VFQ. Estimates of
      internal consistency indicate that the subscales of the NEI VFQ-25 are reliable.
      The validity of the NEI VFQ-25 is supported by high correlations between the
      short- and long-form versions of the measure, observed between-group differences
      in scores for persons with different eye diseases of varying severity, and the
      moderate-to-high correlations between the NEI VFQ-25 subscales that have the most
      to do with central vision and measured visual acuity. CONCLUSIONS: The
      reliability and validity of the NEI VFQ-25 are comparable to those of the 51-item
      NEI VFQ field test version of the survey. This shorter version will be more
      feasible in settings such as clinical trials where interview length is a critical
      consideration. In addition, preliminary analyses indicate that the psychometric
      properties of the NEI VFQ-25 are robust for the eye conditions studied; this
      suggests that the measure will provide reproducible and valid data when used
      across multiple conditions of varying severity.

PMID- 11448328
TI  - A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus
      albipunctatus associated with cone dystrophy.
AB  - OBJECTIVE: To assess the clinical and genetic characteristics of a Japanese
      family with fundus albipunctatus with progressive cone dystrophy associated with
      a mutation in the RDH5 gene. DESIGN: Case report with clinical findings and
      results of fluorescein angiography, electroretinograms, kinetic visual field
      testing, dark adaptometry, and DNA analysis. SETTING: University medical center.
      PATIENTS: We studied the ocular findings in 6 members of a Japanese family with
      fundus albipunctatus with cone dystrophy and a guanine-to-adenine transversion at
      the first nucleotide in codon 35 of the RDH5 gene. The mutation resulted in a
      substitution of serine for glycine in amino acid 35 (Gly35Ser) of the RDH5 gene.
      RESULTS: Characteristic features included poor night vision, white dots in the
      retina, cone dystrophy, and a mottled appearance of the retinal pigment
      epithelium. Electroretinograms showed greater impairment of the rod-mediated
      responses than the cone-mediated responses. After 3 hours of dark adaptation, the
      a and b waves and scotopic b waves recovered. CONCLUSIONS: Although the mutation
      of the RDH5 gene has been known as a causative gene of fundus albipunctatus, the
      Gly35Ser mutation in the RDH5 gene may be related to the pathogenesis of
      progressive retinal degeneration. This phenomenon may provide evidence of gene
      phenotype caused by a mutation in the RDH5 gene. CLINICAL RELEVANCE: The Gly35Ser
      mutation causes fundus albipunctatus with cone dystrophy. This finding provides
      evidence that some kinds of mutations in the RDH5 gene are related, in part at
      least, to the pathogenesis of progressive retinal degeneration.

PMID- 11448329
TI  - Double fault! Ocular hazards of a tennis sunglass.

PMID- 11448330
TI  - Fifteen years of work: the COMS outcomes for medium-sized choroidal melanoma.

PMID- 11448331
TI  - Early detection of moderate glaucoma: redefining clinical care in 2001.

PMID- 11448332
TI  - Proboscis lateralis.

PMID- 11448333
TI  - Late occurrence of diffuse lamellar keratitis after laser in situ keratomileusis.

PMID- 11448334
TI  - Retinal degeneration associated with congenital transcobalamin II deficiency.

PMID- 11448335
TI  - Interferon-associated retinopathy and cystoid macular edema.

PMID- 11448336
TI  - Prophylaxis of vasovagal reaction with Atrohist Plus.

PMID- 11448338
TI  - Inadvertent staining of the posterior lens capsule with trypan blue dye during
      phacoemulsification.

PMID- 11448339
TI  - Additional factors linking corneal melting to topical nonsteroidal anti
      inflammatory drugs.

PMID- 11448341
TI  - Increasing the efficiency of photodynamic therapy in the treatment of subretinal
      neovascularization.

PMID- 11448344
TI  - Tragic optimism vs learning on the verge of more change and great advances:
      presidential address, American Head and Neck Society.

PMID- 11448345
TI  - Dr Martin: how are we doing in 2000? Hayes Martin lecture.

PMID- 11448346
TI  - Nasopharyngeal cancer: current status of management: a New York Head and Neck
      Society lecture.
AB  - Over the last decade, we have made significant progress in treating
      nasopharyngeal cancer. We have achieved a better tumor control rate with
      conformal radiotherapy and chemotherapy. Surgical salvage treatment has also
      contributed to helping patients with localized disease in the neck or in the
      nasopharynx.

PMID- 11448347
TI  - Symptom-directed selective endoscopy: long-term efficacy.
AB  - BACKGROUND: Synchronous primary neoplasms have been encountered in some patients
      with mucosal squamous cell carcinoma of the head and neck. Routine panendoscopy
      along with various radiological tests have been advocated to identify these
      potential tumors. In 1993, we originally described symptom-directed, selective
      endoscopy as an efficient and cost-effective means to evaluate patients to
      identify synchronous primary neoplasms. OBJECTIVE: To review the ultimate success
      rate of symptom-directed, selective endoscopy in that initial cohort of patients
      and the success of the program longitudinally in clinical practice over the
      intervening 6 years. PATIENTS AND METHODS: The status of the original 100
      patients who participated in the selective endoscopy study were reviewed at least
      6 months after the original procedure. A statistically significant random sample
      of 101 subsequent patients who had at least 6 months' follow-up or until their
      death were reviewed. RESULTS: No additional primary, mucosal head and neck,
      esophageal, or pulmonary cancers were identified in the surviving original cohort
      of patients suggesting that the selective endoscopy identified all synchronous
      tumors. Sixteen metachronous primary cancers were identified between 12 and 70
      months after the initial evaluation. Eight synchronous primary cancers were
      identified in the new cohort using symptom-directed evaluation, direct
      laryngopharyngoscopy, and chest x-ray films. No additional tumors were detected
      within 6 months. CONCLUSION: Symptom-directed, selective endoscopy seems to be an
      effective alternative to routine panendoscopy in identifying synchronous primary
      cancers.

PMID- 11448348
TI  - Clinical experience with HLA-B7 plasmid DNA/lipid complex in advanced squamous
      cell carcinoma of the head and neck.
AB  - OBJECTIVE: To investigate the safety and efficacy of alloantigen plasmid DNA
      therapy in patients with advanced head and neck squamous cell carcinoma using
      Allovectin-7 (Vical Inc, San Diego, Calif), a DNA/lipid complex designed to
      express the class I major histocompatibility complex antigen HLA-B7. DESIGN:
      Multi-institutional prospective trial. SETTING: Academic medical setting.
      PATIENTS: A total of 69 patients were enrolled in 3 sequential clinical trials: a
      single-center phase 1 trial and 2 multicenter phase 2 trials. Eligibility
      criteria included unresectable squamous cell carcinoma that failed conventional
      therapy, Karnofsky performance status score of 70 or greater, and no concurrent
      anticancer or immunosuppressive therapies. INTERVENTION: Patients received 2
      biweekly intratumoral injections of 10 microg (phase 1 and first phase 2 trials)
      or 100 microg (second phase 2 trial) of Allovectin-7 followed by 4 weeks of
      observation. Patients with stable or responding disease after the observation
      period were given a second treatment cycle identical to the first. MAIN OUTCOME
      MEASURES: Patients were assessed for toxic effects, and tumor size was measured
      after cycles 1 (at 6 weeks) and 2 (at 16 weeks). RESULTS: Allovectin-7 treatment
      was well tolerated, with no grade 3 or 4 drug-related toxic effects. Of 69
      patients treated, 23 (33%) had stable disease or a partial response after the
      first cycle of treatment and proceeded to the second cycle. After the second
      cycle, 6 patients had stable disease, 4 had a partial response, and 1 had a
      complete response. Responses persisted for 21 to 106 weeks. CONCLUSIONS:
      Intratumoral plasmid DNA immunotherapy for head and neck cancer with Allovectin-7
      is safe, and further investigations are planned in patients with less advanced
      disease, where it could potentially improve patient survival and reduce the need
      for radical high-morbidity treatments.

PMID- 11448349
TI  - Molecular marker expression in oral and oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVE: To determine the relative prognostic value of p53, cyclin D1,
      epidermal growth factor receptor (EGFR), and vascular endothelial growth factor
      (VEGF) expression in patients with oral and oropharyngeal squamous cell
      carcinoma. DESIGN: Retrospective cohort study. PATIENTS: Fifty-six patients with
      oral and oropharyngeal squamous cell carcinoma referred to the Department of
      Therapeutic Radiology at Yale-New Haven Hospital (Conn) between 1981 and 1992 who
      were treated with gross total surgical resection and postoperative external beam
      radiotherapy. RESULTS: Archival tumor tissue was stained with monoclonal
      antibodies directed against these 4 oncoproteins and scored for staining
      intensity and percent distribution by a pathologist blinded to the patients'
      clinical outcomes. Frequency of marker expression was 48% for p53, 20% for cyclin
      D1, 64% for EGFR, and 41% for VEGF. In multivariate analysis, EGFR positivity was
      protective against locoregional relapse (relative risk [RR], 0.27; 95% confidence
      interval [CI], 0.11-0.66; P =.002). In contrast, advanced N stage predicted poor
      locoregional relapse-free survival (RR, 1.94; 95% CI, 1.03-3.66; P =.04).
      Predictors of poor overall survival in multivariate analysis included VEGF
      positivity (RR, 3.53; 95% CI, 1.75-7.13; P<.001) and black race (RR, 2.48; 95%
      CI, 1.05-5.85; P =.04). Cyclin D1 and p53 expression were not significantly
      associated with prognosis in this cohort. CONCLUSIONS: In oral and oropharyngeal
      squamous cell carcinoma treated with surgery and postoperative radiotherapy, VEGF
      and EGFR expression may influence clinical outcome. If confirmed, these results
      have potential implications for the determination of patient prognosis and the
      development of biologically based pharmacotherapies.

PMID- 11448350
TI  - Salvage resection after previous laryngeal surgery: total laryngectomy with en
      bloc resection of the overlying cervical skin.
AB  - OBJECTIVE: To evaluate the effectiveness of extended total laryngectomy for the
      treatment of recurrences of laryngeal cancer. DESIGN: We conducted a
      retrospective clinical study of patients who had undergone extended total
      laryngectomy and were seen over a 15-year period. The follow-up period ranged
      from 3 to 15 years. SETTING: Academic tertiary referral medical center. PATIENTS:
      We observed 15 patients who were affected by a recurrence of laryngeal cancer
      that extended to the overlying soft tissue. All patients were male. The mean age
      was 61.5 years. Thirteen patients had previously undergone partial laryngeal
      surgery, and 2 patients had undergone radiation therapy, without success.
      INTERVENTION: All patients underwent total laryngectomy extending to the soft
      tissue, including the overlying skin. RESULTS: Five of the 15 patients died of
      local recurrence, and 1 patient died of massive postoperative hemorrhaging. An
      actuarial survival rate of 60% was observed at 5 years. CONCLUSION: Total
      laryngectomy extending to the soft tissues seems to be an effective procedure for
      treating local recurrences of laryngeal cancer after partial laryngectomy or
      failure of radiation therapy.

PMID- 11448351
TI  - Intraoperative microwave processing of bone margins during resection of head and
      neck cancer.
AB  - OBJECTIVE: To develop an accurate method for performing histopathologic analysis
      for a full cross-section of cortical bone within 2 to 3 hours. METHODS: Microwave
      technology was used to augment and to more rapidly perform fixation and
      decalcification of cortical bone. RESULTS: Using the methods described, slides
      suitable for histopathologic analyses regarding the presence or absence of
      malignant tumor were prepared in 2 to 3 hours and, in 10 patients studied, had a
      100% correlation with slides prepared in 7 days using the standard
      decalcification technique. CONCLUSION: Microwave technology allows accurate
      assessment of a full cross-section of cortical bone regarding the presence or
      absence of malignant tumor within the time limits required for resection of a
      malignant head and neck tumor and reconstruction of the surgical defect.

PMID- 11448352
TI  - Primary intraosseous carcinoma of the jaws.
AB  - OBJECTIVES: To present 8 new cases of primary intraosseous carcinoma of the jaws
      and to review the literature for an analysis of treatment modalities and patient
      outcomes. DATA SOURCES: A MEDLINE search from 1970 to 1999. The articles chosen
      and the study of the references of every one that produced additional articles
      provided database information for 28 patients. Eight new patients from our
      institutions were added. STUDY SELECTION: Our criteria of inclusion included the
      absence of ulceration of the oral mucosa, a negative result in the search for a
      distant primary tumor, and convincing histological documentation. DATA
      EXTRACTION: The variables of the analysis included age, sex, site of the tumor,
      condition of the oral mucosa, tumor size, neck status, treatment modalities,
      recurrences, and survival. DATA SYNTHESIS: Twenty-eight patients were identified
      in the literature, for a total of 36 patients. There were 28 males (78%) and 8
      females (22%) ranging in age from 4 to 76 years (mean, 54 years). The tumor site
      was the mandible in 33 patients (92%) and the maxilla in 3 (8%). Of the 34
      patients treated, 19 (56%) had recurrences. Overall 2- and 4-year survival was
      60.5% and 39.9%, respectively. Patients who underwent radical surgery and
      postoperative radiotherapy (n = 11) had a 2- and 3-year survival probability of
      61.3% and 40.9%, respectively, whereas in the remaining patients (n = 25), the
      rates were 59.7% and 31.3%, respectively (P =.60). CONCLUSIONS: Strict diagnostic
      criteria must be applied. The prognosis associated with primary intraosseous
      carcinoma of the jaws is poor and suggests the need for aggressive treatment.

PMID- 11448353
TI  - Factors affecting the overall survival after salvage surgery in patients with
      recurrent nasopharyngeal carcinoma at the primary site: experience with 60 cases.
AB  - OBJECTIVE: To analyze the factors affecting overall survival after salvage
      surgery in patients with recurrent nasopharyngeal carcinoma at the primary site
      after a full course of radiotherapy. DESIGN: Retrospective analysis of 60
      consecutive patients treated by surgical resection of the recurrent tumors, with
      a mean follow-up of 43.1 months (range, 19-96 months). SETTING: Academic tertiary
      referral center. RESULTS: The overall survival and locoregional relapse-free
      survival were 56% and 60% at 2 years, respectively, and 30% and 40% at 5 years.
      Twenty-nine (81%) of 36 patients died with uncontrolled local disease. The T
      stage of the recurrent tumors appeared to be an important prognostic factor. Age,
      sex, pathologic findings, and disease-free interval (time between previous
      radiotherapy and local recurrence) were not significant prognosis-affecting
      factors by the log-rank test. Multivariate analysis showed that patients with
      recurrent tumors of undifferentiated carcinoma, sarcoma, or small cell carcinoma
      had unfavorable prognoses. Uncontrolled local disease and the emergence of
      distant metastasis predicted grave results as well. Postoperative irradiation
      showed some benefit to patients, but the difference was not statistically
      significant. CONCLUSIONS: The T stage of the recurrence was the prominent
      prognosis-affecting factor in patients with recurrent nasopharyngeal carcinoma
      who received salvage surgery. Patients with local recurrence should be carefully
      selected for the salvage surgery. We recommend this surgery for patients with
      rT1, rT2, or limited rT3 lesions. The results of surgical resection in terms of
      local control and overall survival were slightly better than those of high-dose
      reirradiation, with fewer late complications.

PMID- 11448354
TI  - Squamous cell carcinoma of the temporal bone: a radiographic-pathologic
      correlation.
AB  - OBJECTIVE: To assess the utility of a previously proposed staging system for
      patients with primary squamous cell carcinoma of the temporal bone. METHODS:
      Retrospective chart review of 15 patients treated for squamous cell carcinoma of
      the temporal bone over a 13-year period at an academic tertiary referral center.
      A review of the medical and surgical records, radiographic studies, and surgical
      pathology reports allowed for an evaluation of the University of Pittsburgh
      staging system. Outcome analysis was performed on 13 patients with more than 24
      months of follow-up. RESULTS: Radiographic and surgical pathology staging
      according to the University of Pittsburgh staging system correlated in 11 (73%)
      of 15 cases. The radiographic staging system was more accurate for larger (T3/T4)
      tumors than for smaller (T1/T2) tumors (83% vs 67%). When compared with patients
      with no evidence of disease, nonsurvivors were more likely to present with
      otalgia (67% vs 43%), facial nerve paralysis (33% vs 0%), and T3/T4 tumors (100%
      vs 14%). CONCLUSIONS: Pathologic staging by the University of Pittsburgh staging
      system closely correlates with patient outcome and is more sensitive than
      preoperative radiographic staging. Prognosis in squamous cell carcinoma of the
      temporal bone is largely determined by the extent of local disease at the time of
      presentation.

PMID- 11448355
TI  - High-dose intra-arterial cisplatin therapy followed by radiation therapy for
      advanced squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: To assess the effectiveness of a protocol consisting of 4 cycles of
      high-dose intra-arterial cisplatin infusions followed by radiation therapy for
      improving chemotherapy response rates, organ preservation, and survival in
      patients with advanced-stage untreated and previously treated squamous cell
      carcinoma of the head and neck. DESIGN AND SETTING: A prospective study of
      sequentially enrolled patients treated in an academic medical center. The Kaplan
      Meier method was used for survival analysis. PATIENTS: Fifty-eight nonpregnant
      adults, 18 years of age or older, with measurable untreated or recurrent advanced
      biopsy-proven squamous cell carcinoma of the head and neck. MAIN OUTCOME
      MEASURES: Response rate to targeted intra-arterial cisplatin infusions, organ
      preservation, and survival. RESULTS: Fifty-eight patients (44 men and 14 women)
      were followed up for at least 2 years (median duration of follow-up, 27 months).
      Twenty-nine (67%) of the 43 previously untreated patients had a complete response
      to intra-arterial cisplatin therapy. Of the untreated patients, 28 are alive and
      disease free after a median follow-up time of 30 months. Five of the patients
      with recurrent disease had a complete response to intra-arterial cisplatin
      therapy. There were 4 survivors after a median follow-up time of 17.5 months. Of
      note, there were no deaths or serious complications related to the treatment in
      either group. CONCLUSIONS: High-dose intra-arterial cisplatin therapy provides a
      high complete and partial response rate (91%). The combination of high-dose intra
      arterial cisplatin and radiation therapy is effective in improving survival and
      organ preservation rates in patients with previously untreated, advanced squamous
      cell carcinoma of the head and neck. This treatment protocol is much less
      effective for recurrent disease.

PMID- 11448356
TI  - Expression of matrix metalloproteinases and their inhibitors correlates with
      invasion and metastasis in squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the invasion
      and metastasis of head and neck squamous cell carcinoma (HNSCC). However, a
      detailed analysis of MMPs and tissue inhibitors of MMPs (TIMPs) in relation to
      the biological behavior of HNSCC has yet to be performed in clinical material.
      OBJECTIVES: To study a comprehensive profile of MMPs and their 2 main inhibitors
      in HNSCC tissue samples and to correlate the patterns of expression with
      clinicopathological characteristics, invasion, and metastasis. DESIGN: This study
      included 54 consecutive patients with primary HNSCC, 27 of which showed lymph
      node metastasis. Expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-11,
      MMP-13, MMP-14, TIMP-1, and TIMP-2 was simultaneously analyzed in tissue
      homogenates using semiquantitative reverse transcription-polymerase chain
      reaction assay. Where feasible, levels of protein and enzyme activity were
      confirmed by Western blot, enzyme-linked immunosorbent assay, and substrate
      zymography. Conventional clinicopathological features, including mode of tumor
      invasion, were also examined. RESULTS: Significantly higher MMP-1, MMP-2, MMP-3,
      MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, and TIMP-1 levels were found in tumors vs
      specimens of matched normal mucosa. No difference in the distribution of MMPs and
      TIMPs in relation to age, sex, tumor site, or histological grade was observed. A
      significant correlation was demonstrated between levels of MMP-1, MMP-9, and TIMP
      1 and advanced T stage and between MMP-9 expression and an infiltrative pattern
      of growth. Enhanced expression of MMP-9 was strongly correlated (P<.001) and
      levels of MMP-2, MMP-7, and MMP-11 were weakly correlated (P =.03-.05) with lymph
      node involvement. CONCLUSIONS: Overexpression of multiple MMPs and TIMPs is
      characteristic of HNSCC, and analysis of specific MMPs, MMP-9 in particular,
      might be useful for evaluating the malignant potential in individual HNSCC.

PMID- 11448357
TI  - The influence of intraoperative parathyroid hormone monitoring on the surgical
      management of hyperparathyroidism.
AB  - OBJECTIVE: To examine the role of intraoperative rapid parathyroid hormone (PTH)
      monitoring in the surgical management of hyperparathyroidism. DESIGN: Thirty
      eight-month retrospective review. SETTING: Tertiary care academic medical center.
      PATIENTS: One hundred consecutive patients undergoing surgery for primary
      hyperparathyroidism. INTERVENTION: All patients underwent preoperative technetium
      Tc 99m sestamibi scan localization and intraoperative blood PTH monitoring by
      means of a rapid (12-minute) immunochemiluminometric assay. MAIN OUTCOME
      MEASURES: The influence of intraoperative PTH levels on extent of surgical
      dissection and achievement of postoperative normocalcemia. RESULTS:
      Intraoperative PTH levels dropped an average of 64%, 75%, and 83% at 5, 10, and
      20 minutes, respectively, after excision of all hyperfunctioning parathyroid
      tissue. A PTH decrease of 46% or more at 10 minutes and 59% or more at 20 minutes
      after excision of hyperfunctioning tissue was predictive of postoperative
      normocalcemia. In 79 patients (79%), the sestamibi scan provided accurate
      preoperative localization; all but 1 of these patients were treated successfully,
      most often with a limited, gland-specific dissection. In 24 patients with
      inaccurate, negative, or misleading preoperative sestamibi scans, 23 (96%) were
      treated successfully with the use of the intraoperative PTH assay. CONCLUSIONS:
      The rapid intraoperative PTH assay accurately predicts postoperative success in
      patients with primary hyperparathyroidism. The rapid PTH assay allows for greater
      confidence in performing limited dissections in well-localized uniglandular
      disease. In cases of inaccurate preoperative localization, the rapid PTH assay
      directly affects surgical decision making and provides greater confidence in
      determining when surgical success has been achieved.

PMID- 11448358
TI  - Risk factors for postoperative complications in oral cancer and their prognostic
      implications.
AB  - BACKGROUND: The surgical treatment of head and neck cancer can be limited by the
      risk of postoperative complications. Early identification of risk factors based
      on clinical characteristics may assist therapeutic planning. OBJECTIVES: To
      identify risk factors for these complications and to evaluate their prognostic
      significance. METHODS: The medical records of 110 patients with oral squamous
      cell carcinoma admitted from January 1, 1990, to December 31, 1994, who underwent
      radical surgery were reviewed. Data collected included demographic information,
      comorbidities, extended clinical severity stage, treatment, complications, and
      survival. The chi(2) test was used to verify the association between the
      variables. Survival analysis was performed with the Kaplan-Meier method. Logistic
      and Cox proportional hazards regression were used to build models with
      independent predictive factors for the risk of complications and death,
      respectively. RESULTS: The overall complication rate was 50%. Dehiscence and
      infection rates were 20.9% and 22.7%, respectively. The death rate was 3.6%.
      Forty-seven patients (42.7%) were electively referred to the intensive care unit
      (ICU). The occurrence of postoperative complications was associated with extended
      clinical severity stage (P =.02), type of surgery (P =.03), ICU (P =.03), type of
      reconstruction (P =.02), Functional Severity Index (P =.03), neck dissection (P
      =.002), and APACHE II (Acute Physiology and Chronic Health Evaluation II) (P
      =.008). The number of complications was significantly correlated with the length
      of hospital stay (r = 0.24, P =.01) and with the Functional Severity Index (r =
      0.19, P =.04). Five-year overall survival was affected by the type of
      complications (none, 41.7%; local, 34.1%; and local plus systemic, 0% [P<.001]),
      ICU (no, 46.3%; yes, 20.7% [P =.001]), and extended clinical severity stage
      (stage 1, 75.6%; stage 2, 50%; stage 3, 28.6%; and stage 4, 10.2% [P<.001]). In a
      multivariate analysis bilateral neck dissection (relative risk = 3.57, P =.01)
      and an APACHE II score greater than 10 (relative risk = 3.86, P =.02) were
      independent risk factors for complications. The predictive prognostic model
      consisted of the following: staying in the ICU (hazard ratio = 1.83), local plus
      systemic complications (hazard ratio = 6.27), and extended clinical severity
      stage (stage 3, hazard ratio = 3.57; stage 4, hazard ratio = 6.34). CONCLUSIONS:
      Bilateral neck dissection and the APACHE II score were identified as risk factors
      for postoperative complications in oral cancer, which also increase the length of
      hospital stay. The occurrence of systemic complications, advanced extended
      clinical severity stage, and staying in an ICU adversely affect the prognosis.
      Therefore, the prompt recognition of the adverse risk factors for postoperative
      complications may guide proactive interventions that may improve survival and
      achieve cost-effectiveness.

PMID- 11448359
TI  - Intraoperative fabrication of palatal prosthesis for maxillary resection.
AB  - BACKGROUND: Immediate placement of a palatal prosthesis has become the standard
      of care after maxillectomy or palatectomy, except when free-flap reconstruction
      is used. Palatal prostheses are usually fabricated preoperatively. Infrequently,
      the surgeon may face a situation where upper jaw resection has been performed and
      a prefabricated prosthesis is not available. OBJECTIVE: To describe a method of
      rapid intraoperative fabrication of a palatal prosthesis, which allows immediate
      oral intake and excellent speech. PROCEDURE: Two sheets of thermoplastic dressing
      (Aquaplast; WFR/Aquaplast Corporation, Wyckoff, NJ) were immersed in hot water.
      As they became soft and pliable, they were applied to the remaining hard palate
      and alveolar ridge. As the material cooled, it hardened, with its shape
      conforming to the remaining hard palate, alveolar ridge, and teeth. The rigid
      stent was then removed, trimmed, and fashioned to cover the palatal and maxillary
      defect. The stent was then wired to the remaining alveolar ridge and to the
      ipsilateral zygomatic buttress or lateral orbital rim. Removal of the stent was
      easily accomplished in an office setting. PATIENTS: Twelve patients required
      partial upper jaw resection without available prefabricated prostheses. Of these,
      3 patients underwent emergency surgery for mucormycosis and 2 for bleeding
      malignant tumors; 3 underwent bone resection more extensive than that anticipated
      preoperatively; and 4 did not have prefabricated prostheses for other reasons.
      RESULTS: The thermoplastic prosthesis achieved its goals in all 12 patients.
      Eleven patients achieved oral food intake within 24 hours. One patient remained
      in a coma after extensive maxillary, orbital, and skull base resection for
      mucormycosis. The prosthesis was removed after 4 to 12 weeks and replaced with a
      permanent implant in 11 of the 12 patients. CONCLUSIONS: This simple, quick, and
      inexpensive intraoperative fabrication of palatal prosthesis requires no special
      expertise and equipment. It allows immediate oral intake and excellent speech.

PMID- 11448360
TI  - The palatal island flap for reconstruction of palatal and retromolar trigone
      defects revisited.
AB  - BACKGROUND: Although a host of local soft tissue flaps have been described for
      the reconstruction of postoperative palatal defects, tissue-borne palatal
      obturators remain the most common form of rehabilitation of these defects. The
      palatal island flap, first applied to the reconstruction of the retromolar
      trigone and palatal defects, was first described by Gullane and Arena in 1977.
      This single-staged mucoperiosteal flap offers a reliable source of regional
      vascularized soft tissue that obviates the need for prosthetic palatal
      rehabilitation. OBJECTIVE: To describe a series of 5 cases in which the palatal
      island flap was used as a primary palatal or retromolar reconstruction. METHODS:
      We have retrospectively reviewed 5 consecutive cases between March 1998 and
      August 1999 wherein palatal island flaps were used for the primary reconstruction
      of postablative palatal defects. Each case was reviewed for primary pathologic
      findings, postoperative wound complications, postoperative speech and swallowing,
      and donor site morbidity. Selection of this reconstructive technique was based on
      the size and location of the defect and the assessment by the surgeon that the
      arc of rotation and amount of residual palatal mucosa were appropriate. RESULTS:
      Six local palatal island flaps were performed on 5 patients who had not undergone
      irradiation (1 patient underwent bilateral flaps). The primary pathologic
      findings included T1 N0 squamous cell carcinoma, T4 N0 squamous cell carcinoma,
      T2 N0 low-grade mucoepidermoid carcinoma, pigmented neurofibroma, and T2 N0 low
      grade clear cell carcinoma. All of the lesions were located on the hard or soft
      palate or the retromolar trigone, and the average defect size was 7.2 cm(2). All
      5 patients began an oral diet between postoperative days 1 and 5 (mean, 2 days),
      and all patients were discharged home without postoperative donor site or
      recipient site complications between days 1 and 6 (mean, 3 days). Donor site
      reepithelialization was complete by 4 weeks in all 5 patients. CONCLUSIONS: The
      palatal island flap offers a reliable method of primary reconstruction for
      limited lesions of the retromolar trigone and hard and soft palate. The
      mucoperiosteal tissue associated with this flap is ideal for partitioning the
      oral and nasal cavities and obviates the need for prosthetic palatal obturation.

PMID- 11448361
TI  - Condylar prostheses in head and neck cancer reconstruction.
AB  - OBJECTIVE: To discuss the use of condylar prostheses after mandibular resection
      for tumor. DESIGN: Case series and literature review. SETTING: Tertiary referral
      center. PATIENTS: Four patients underwent condylar reconstruction with metallic
      condylar prostheses after hemimandibulectomy for either squamous cell cancer or
      Ewing sarcoma. MAIN OUTCOME MEASURE: Complications related to the condylar
      prostheses. RESULTS: Clinical and radiological follow-up in these patients
      revealed several complications, including exposure or extrusion of the prosthesis
      and migration of the prosthesis into the epitympanum, resulting in profound
      sensorineural hearing loss owing to bony destruction of the cochlea. Two of our
      patients required removal of the mandibular hardware because of the seriousness
      of the complications, and 1 of the 2 underwent reconstruction of the condyle with
      a fibular free flap. CONCLUSIONS: Metallic condylar prostheses in the setting of
      tumor resection and reconstruction involve significant risks. Autogenous
      materials, such as vascularized bone grafts, should be used whenever possible.

PMID- 11448362
TI  - Tubed gastro-omental free flap for pharyngoesophageal reconstruction.
AB  - BACKGROUND: Malignant lesions of the pharyngoesophagus often require total
      laryngopharyngectomy and mediastinal dissection. As a result of the current
      treatment paradigms for advanced laryngopharyngeal cancers, it is common that the
      surgical field has been previously irradiated or exposed to systemic
      chemotherapy, resulting in fistula rates as high as 78% and mortality as high as
      8%. The free vascularized tubed gastric antrum and the accompanying greater
      omentum offer a single-staged method of pharyngoesophageal reconstruction, with
      the added benefit of protection of the great vessels, the tracheal stump, and the
      mediastinal contents in a high-risk surgical field. OBJECTIVE: To assess the
      gastro-omental free flap as a method of pharyngoesophageal reconstruction in
      patients who have been previously treated with multimodality therapy. METHODS:
      Five consecutive cases of gastro-omental free flap reconstruction after total
      laryngopharyngectomy were retrospectively reviewed. Each case was assessed for
      intraoperative, perioperative, and postoperative complications at the primary
      site of reconstruction and the donor site. Patients were also evaluated for their
      ability to maintain an oral diet. Patients were followed up for a minimum of 6
      months after surgery. RESULTS: Five patients aged 44 to 70 years (mean, 59 years)
      underwent gastro-omental free flap reconstruction after total
      laryngopharyngectomy. Five patients had received previous external beam
      irradiation, 2 had received systemic chemotherapy, and 4 had undergone previous
      surgery. There were no fistulae or flap complications. Three patients were
      successfully treated with esophageal dilation for strictures sustained 2 to 5
      months after surgery, and a third patient was successfully treated with
      conservative management for a partial gastric outlet obstruction sustained 2
      months after surgery. One patient died 3 months after surgery of distant
      metastatic disease. The remaining 4 patients currently tolerate an oral diet.
      CONCLUSION: The tubed gastro-omental free flap offers a safe method of
      reconstructing the pharyngoesophageal segment in a surgical field compromised by
      previous multimodality therapy.

PMID- 11448363
TI  - Iliac crest internal oblique osteomusculocutaneous free flap reconstruction of
      the postablative palatomaxillary defect.
AB  - BACKGROUND: Traditionally, restoration of extensive palatomaxillary defects have
      been achieved by prosthetic restoration, often with suboptimal functional
      results. More recently, vascularized bone-containing free flaps have been used
      for this purpose. OBJECTIVE: To describe 6 patients who underwent palatomaxillary
      reconstruction using the composite iliac crest-internal oblique
      osteomusculocutaneous free flap. METHODS: Six cases of iliac crest
      osteomusculocutaneous free flap reconstruction of extensive postablative
      palatomaxillary defects were retrospectively reviewed with clinical follow-up. We
      reviewed these cases for pathologic findings, defect size, dental restoration,
      oral rehabilitation, and speech. RESULTS: Pathologic findings included squamous
      cell carcinoma (n = 4), osteogenic sarcoma (n = 1), and sinonasal
      hemangiopericytoma (n = 1). Mean follow-up was 14.5 months (range, 10-25 months).
      Four patients underwent resection and reconstruction primarily and 2 underwent
      reconstruction secondarily. Two patients required reconstruction of a cutaneous
      defect using the iliac skin paddle. The hard palate and lateral nasal wall were
      reconstructed in all 6 patients, and the orbital rim and zygomatic body were
      reconstructed in 4. One patient underwent reconstruction with an orbital
      prosthesis supported by osseointegrated implants. There was 1 donor site
      complication and 1 recipient site infection, which was treated successfully with
      oral antibiotics. Four patients were rehabilitated with osseointegrated implants,
      and all 6 patients maintain an unrestricted oral diet. All 6 patients have normal
      speech without velopharyngeal or oronasal insufficiency. CONCLUSION: For
      extensive palatomaxillary defects, the iliac crest-internal oblique
      osteomusculocutaneous free flap offers a reliable method of primary
      reconstruction, allowing for complete orodental rehabilitation without the use of
      a prosthetic obturator.

PMID- 11448364
TI  - The scapular osteofasciocutaneous flap: a 12-year experience.
AB  - OBJECTIVE: To elucidate the factors that play a role in the decision-making
      process to use the scapular donor site, we have reviewed our 15-year experience
      with 57 clinical cases, to our knowledge the largest case series to date. DESIGN:
      Retrospective, single-surgeon medical record review. PATIENTS AND METHODS:
      Retrospective review of 57 consecutive cases (53 patients) involving mandibular
      and maxillary reconstruction using bone-containing scapular free flaps over a 15
      year period. Composite flap composition as well as donor and recipient site
      complications were recorded. RESULTS: Forty-one reconstructions were performed
      for mandibular defects, 11 were performed for maxillary defects, and 5 for
      combined defects involving the mandible and maxilla. Seven flaps were composed of
      2 separate bone flaps using the angular branch and the circumflex scapular
      artery. A total of 6 flaps were failures in 5 patients, giving an overall success
      rate of 89%. CONCLUSIONS: The subscapular system of flaps is a versatile donor
      site that offers distinct advantages in the older patient population as well as
      in patients with a preexisting gait disturbance. It is particularly advantageous
      in patients requiring a large surface area of soft tissue to restore their
      defect.

PMID- 11448365
TI  - The development and validation of a dysphagia-specific quality-of-life
      questionnaire for patients with head and neck cancer: the M. D. Anderson
      dysphagia inventory.
AB  - OBJECTIVE: To design a reliable and validated self-administered questionnaire
      whose purpose is to assess dysphagia's effects on the quality of life (QOL) of
      patients with head and neck cancer. DESIGN: Cross-sectional survey study.
      METHODS: Focus groups were convened for questionnaire development and design. The
      M. D. Anderson Dysphagia Inventory (MDADI) included global, emotional,
      functional, and physical subscales. One hundred consecutive adult patients with a
      neoplasm of the upper aerodigestive tract who underwent evaluation by our Speech
      Pathology team completed the MDADI and the Medical Outcomes Study 36-Item Short
      Form Health Survey (SF-36). Speech pathologists completed the Performance Status
      Scale for each patient. Validity and reliability properties were calculated.
      Analysis of variance was used to assess how well the MDADI discriminated between
      groups of patients. RESULTS: The internal consistency reliability of the MDADI
      was calculated using the Cronbach alpha coefficient. The Cronbach alpha
      coefficients of the MDADI subscales ranged from 0.85 to 0.93. Test-retest
      reliability coefficients of the subscales ranged from 0.69 to 0.88. Spearman
      correlation coefficients between the MDADI subscales and the SF-36 subscales
      demonstrated construct validity. Patients with primary tumors of the oral cavity
      and oropharynx had significantly greater swallowing disability with an adverse
      impact on their QOL compared with patients with primary tumors of the larynx and
      hypopharynx (P<.001). Patients with a malignant lesion also had significantly
      greater disability than patients with a benign lesion (P<.001). CONCLUSIONS: The
      MDADI is the first validated and reliable self-administered questionnaire
      designed specifically for evaluating the impact of dysphagia on the QOL of
      patients with head and neck cancer. Standardized questionnaires that measure
      patients' QOL offer a means for demonstrating treatment impact and improving
      medical care. The development and validation of the MDADI and its use in
      prospective clinical trials allow for better understanding of the impact of
      treatment of head and neck cancer on swallowing and of swallowing difficulty on
      patients' QOL.

PMID- 11448366
TI  - Speech intelligibility after glossectomy and speech rehabilitation.
AB  - BACKGROUND: Oral tumor resections cause articulation deficiencies, depending on
      the site, extent of resection, type of reconstruction, and tongue stump mobility.
      OBJECTIVES: To evaluate the speech intelligibility of patients undergoing total,
      subtotal, or partial glossectomy, before and after speech therapy. PATIENTS AND
      METHODS: Twenty-seven patients (24 men and 3 women), aged 34 to 77 years (mean
      age, 56.5 years), underwent glossectomy. Tumor stages were T1 in 3 patients, T2
      in 4, T3 in 8, T4 in 11, and TX in 1; node stages, N0 in 15 patients, N1 in 5,
      N2a-c in 6, and N3 in 1. No patient had metastases (M0). Patients were divided
      into 3 groups by extent of tongue resection, ie, total (group 1; n = 6), subtotal
      (group 2; n = 9), and partial (group 3; n = 12). Different phonological tasks
      were recorded and analyzed by 3 experienced judges, including sustained 7 oral
      vowels, vowel in a syllable, and the sequence vowel-consonant-vowel (VCV). The
      intelligibility of spontaneous speech (sequence story) was scored from 1 to 4 in
      consensus. All patients underwent a therapeutic program to activate articulatory
      adaptations, compensations, and maximization of the remaining structures for 3 to
      6 months. The tasks were recorded after speech therapy. To compare mean changes,
      analyses of variance and Wilcoxon tests were used. RESULTS: Patients of groups 1
      and 2 significantly improved their speech intelligibility (P<.05). Group 1
      improved vowels, VCV, and spontaneous speech; group 2, syllable, VCV, and
      spontaneous speech. Group 3 demonstrated better intelligibility in the pretherapy
      phase, but the improvement after therapy was not significant. CONCLUSIONS: Speech
      therapy was effective in improving speech intelligibility of patients undergoing
      glossectomy, even after major resection. Different pretherapy ability between
      groups was seen, with improvement of speech intelligibility in groups 1 and 2.
      The improvement of speech intelligibility in group 3 was not statistically
      significant, possibly because of the small and heterogeneous sample.

PMID- 11448367
TI  - Quality of life after great auricular nerve sacrifice during parotidectomy.
AB  - OBJECTIVE: To determine the impact of great auricular nerve (GAN) sacrifice
      during parotidectomy on patients' quality of life. DESIGN: Historical cohort
      survey of patients who had undergone GAN sacrifice during parotidectomy. SETTING:
      Tertiary academic otolaryngologic practice. PATIENTS AND METHODS: Fifty-three
      patients who had undergone GAN sacrifice during parotidectomy completed an 8-item
      quality-of-life survey with a 7-point response scale designed to measure outcome
      after GAN sacrifice during parotidectomy. RESULTS: Thirty patients (57%) reported
      experiencing at least 1 abnormal symptom, but the mean number of symptoms
      decreased significantly with time, from a mean of 2.3 during the first year to
      0.2 after 5 years (P<.001). Even among patients experiencing symptoms, 23 (77%)
      reported only a little or no bother caused by the symptoms, and 27 (90%) reported
      no interference or almost none with their daily activities. The degree of bother
      or interference reported had a moderate positive correlation with the number of
      abnormal sensations reported. CONCLUSIONS: The results suggest that, while many
      patients experienced sensory deficits, the overall quality of life was not
      significantly affected after GAN sacrifice during parotidectomy. Patients who
      report multiple abnormal sensations, however, would benefit from additional
      counseling and from reassurance that the number of sensations will diminish with
      time. Further study evaluating the effect of preservation of the posterior branch
      of the GAN during parotidectomy on patients' quality of life is needed.

PMID- 11448368
TI  - Regional brain metabolic changes in patients with major depression treated with
      either paroxetine or interpersonal therapy: preliminary findings.
AB  - BACKGROUND: In functional brain imaging studies of major depressive disorder
      (MDD), regional abnormalities have been most commonly found in prefrontal cortex,
      anterior cingulate gyrus, and temporal lobe. We examined baseline regional
      metabolic abnormalities and metabolic changes from pretreatment to posttreatment
      in subjects with MDD. We also performed a preliminary comparison of regional
      changes with 2 distinct forms of treatment (paroxetine and interpersonal
      psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal
      control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron
      emission tomography scanning before and after 12 weeks. Between scans, subjects
      with MDD were treated with either paroxetine or interpersonal psychotherapy
      (based on patient preference), while controls underwent no treatment. RESULTS: At
      baseline, subjects with MDD had higher normalized metabolism than controls in the
      prefrontal cortex (and caudate and thalamus), and lower metabolism in the
      temporal lobe. With treatment, subjects with MDD had metabolic changes in the
      direction of normalization in these regions. After treatment, paroxetine-treated
      subjects had a greater mean decrease in Hamilton Depression Rating Scale score
      (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but
      both subgroups showed decreases in normalized prefrontal cortex (paroxetine
      treated bilaterally and interpersonal psychotherapy-treated on the right) and
      left anterior cingulate gyrus metabolism, and increases in normalized left
      temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain
      metabolic abnormalities at baseline that tended to normalize with treatment.
      Regional metabolic changes appeared similar with the 2 forms of treatment. These
      results should be interpreted with caution because of study limitations (small
      sample size, lack of random assignment to treatment groups, and differential
      treatment response between treatment subgroups).

PMID- 11448369
TI  - Brain blood flow changes in depressed patients treated with interpersonal
      psychotherapy or venlafaxine hydrochloride: preliminary findings.
AB  - BACKGROUND: Functional brain imaging studies in major depression have suggested
      abnormalities of areas, including the frontal cortex, cingulate gyrus, basal
      ganglia, and temporal cortex. We hypothesized that venlafaxine hydrochloride and
      interpersonal psychotherapy (IPT) might each alter brain blood flow in some or
      all of these areas on sequential single photon emission computed tomography
      (SPECT) scans. METHODS: Twenty-eight men and women aged 30 to 53 years with a DSM
      IV major depressive episode, a 17-item Hamilton Rating Scale for Depression (HAM
      D) rating of 18 or higher, and antidepressant-naive for at least 6 months were
      studied. After baseline (99m)technetium-hexa-methyl-propylene-amine-oxime scan, 1
      T magnetic resonance imaging, and psychometric ratings, patients were assigned to
      different treatments. Thirteen patients had 1-hour weekly sessions of IPT from
      the same supervised therapist (E.M.). Fifteen patients took 37.5 mg twice-daily
      of venlafaxine hydrochloride. Single-photon emission computed tomography scans
      and ratings were repeated at 6 weeks. RESULTS: Both treatment groups improved
      substantially, more so with venlafaxine (mean [SD] HAM-D scores at pretreatment:
      IPT, 22.7 [2.7], and venlafaxine, 22.4 [3.1]; and posttreatment: IPT, 16.2 [7.1],
      and venlafaxine, 10.9 [8.6]). No patients had structural brain abnormalities. On
      analysis with statistical parametric mapping 96, the venlafaxine group showed
      right posterior temporal and right basal ganglia activation (P =.01), while the
      IPT group had limbic right posterior cingulate and right basal ganglia activation
      (P =.01). CONCLUSIONS: This preliminary investigation has shown limbic blood flow
      increase with IPT yet not venlafaxine, while both treatments demonstrated
      increased basal ganglia blood flow. This was, however, a short trial with a small
      sample, no control group, and different symptom reduction in the 2 groups.

PMID- 11448370
TI  - Functional brain circuits in major depression and remission.

PMID- 11448371
TI  - Neuroimaging profiles and the differential therapies of depression.

PMID- 11448372
TI  - Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in
      depression.
AB  - BACKGROUND: Circadian rhythm disturbances are frequently found in depressed
      subjects. Although it has been presumed that these disturbances may reflect a
      disorder of the circadian pacemaker, this has never been established. The
      suprachiasmatic nucleus (SCN) is the pacemaker of the circadian timing system in
      mammals, and arginine vasopressin (AVP) is one of its major neuropeptides. As
      peptide content is often taken as a measure for activity, we hypothesized that a
      decreased number of AVP-immunoreactive (AVP-IR) neurons and amount of AVP
      messenger RNA (mRNA) would be present in the SCN of depressed subjects. METHODS:
      Brains of 11 subjects suffering from major depression (8 cases) and bipolar
      disorder (3 cases), and of 11 controls, matched for sex, age, and clock time at
      death, were collected. The number of AVP-IR neurons in the SCN was determined by
      means of a digitizer (CalComp Inc, Reading, England). The amount of AVP-mRNA
      expression in the SCN was quantified with the Interaktive Bild Analyse System
      image analysis system (Kontron, Munich, Germany). RESULTS: In depressed subjects,
      the number of AVP-IR neurons in the SCN was more than one and a half times higher
      than in controls, while the total masked area of silver grains, as an estimate of
      the amount of AVP-mRNA, was about one half that of controls. CONCLUSIONS:
      Contrary to our hypothesis, an increase in the number of AVP-IR neurons in the
      SCN in depression was found, together with an expected decrease in AVP-mRNA.
      These findings suggest that, in depressed patients, both the synthesis and
      release of AVP in the SCN is reduced, resulting in an impaired functional
      ability. A disbalance between AVP production and transport needs further
      investigation in future studies.

PMID- 11448373
TI  - Prevalence of psychotic disorder and community level of psychotic symptoms: an
      urban-rural comparison.
AB  - BACKGROUND: Urban and rural populations have different rates of psychotic
      illness. If psychosis exists as a continuous phenotype in nature, urban-rural
      population differences in the rate of psychotic disorder should be accompanied by
      similar differences in the rate of abnormal mental states characterized by
      psychotic or psychosislike symptoms. METHODS: A random sample of 7076 individuals
      aged 18 to 64 years were interviewed by trained lay interviewers with the
      Composite International Diagnostic Interview. Approximately half of those with
      evidence of psychosis according to the Composite International Diagnostic
      Interview were additionally interviewed by clinicians. We investigated
      associations between a 5-level urbanicity rating and (1) any DSM-III-R diagnosis
      of psychotic disorder (sample prevalence, 1.5%), (2) any rating of hallucinations
      and/or delusions (sample prevalence, 4.2%), and (3) any rating of psychotic or
      psychosislike symptoms (sample prevalence, 17.5%). RESULTS: Level of urbanicity
      was associated not only with DSM-III-R psychotic disorder (adjusted odds ratio
      [OR] over 5 levels, 1.47; 95% confidence interval [CI], 1.25-1.72), but also,
      independently, with any rating of delusion and/or hallucination (adjusted OR,
      1.28; 95% CI, 1.17-1.40; clinician-assessed psychotic symptoms only: OR, 1.30;
      95% CI, 1.03-1.64) and any rating of psychosislike symptom (adjusted OR, 1.18;
      95% CI, 1.13-1.24). Psychotic symptoms were strongly and independently associated
      with psychotic disorder, regardless of the level of urbanization. CONCLUSIONS:
      Community level of psychotic and psychosislike symptoms may be inextricably
      linked to the prevalence of psychotic disorder. The prevalence of abnormal mental
      states that facilitate development to overt psychotic illness increases
      progressively with level of urbanization.

PMID- 11448374
TI  - Relationship between positive and negative symptoms of schizophrenia and
      schizotypal symptoms in nonpsychotic relatives.
AB  - BACKGROUND: Continuous rather than categorical measures of psychopathology may
      provide greater statistical power to detect susceptibility loci for
      schizophrenia. However, it has not been established that the dimensions of
      schizophrenic symptomatology and personality traits in nonpsychotic individuals
      share etiological factors. We therefore sought to clarify the relationship
      between positive and negative symptoms of schizophrenic probands and dimensions
      of schizotypy in their first-degree relatives. METHODS: In the Roscommon Family
      Study, we examined the ability of positive and negative symptoms in probands to
      predict 7 factors of schizotypy in nonpsychotic relatives using regression
      analysis. These consisted of positive, negative, and avoidant symptoms; odd
      speech; suspicious behavior; social dysfunction; and symptoms of borderline
      personality disorder. We examined 3 proband groups: schizophrenia (n = 127);
      schizophrenia, simple schizophrenia, and schizoaffective disorder (n = 178); and
      all nonaffective psychoses (n = 216), and their nonpsychotic relatives (n = 309,
      477, and 584, respectively). RESULTS: Positive symptoms in all nonaffective
      psychoses probands predicted positive schizotypy (beta = 0.1972, P =.0004),
      social dysfunction (beta = 0.0719, P =.0489), and borderline personality disorder
      symptoms (beta = 0.1327, P =.0084) in relatives, while negative symptoms
      predicted negative schizotypy (beta = 0.2069, P =.0002), odd speech (beta =
      0.2592, P =.0001), suspicious behavior (beta = 0.2749, P =.0001), and social
      dysfunction (beta =.2398, P =.0002). Proband negative symptoms and borderline
      personality disorder symptoms in relatives in the schizophrenia, simple
      schizophrenia, and schizoaffective disorder group were inversely related (beta = 
      0.1185, P =.05). CONCLUSIONS: Positive and negative symptoms in schizophrenia
      predict corresponding schizotypal symptoms in relatives. This provides evidence
      that these schizophrenic symptom factors (1) are etiologically distinct from each
      other and (2) occur on an etiological continuum with their personality-based
      counterparts.

PMID- 11448375
TI  - Congenital malformations, stillbirths, and infant deaths among children of women
      with schizophrenia.
AB  - BACKGROUND: Women with schizophrenia have increased exposure to risk factors for
      congenital malformations, stillbirths, and infant deaths among their children.
      However, the occurrence of these outcomes is unknown. METHODS: The risks of
      stillbirth and infant death among 2230 children of women with schizophrenia were
      compared with the risks among 123 544 children in the general population. The
      risk of congenital malformations among 746 children of women with schizophrenia
      were compared with the risk among 56 106 children in the general population. The
      year of birth, the sex of the child, the mother's age, and parity were included
      in the analyses as potential confounders. We had no information about
      socioeconomic status, smoking status, substance abuse, or psychotropic medication
      use. RESULTS: Children of women with schizophrenia had increased risk of
      postneonatal death (relative risk [RR], 2.76; 95% confidence interval [CI], 1.67
      4.56). This was largely explained by an increased risk of sudden infant death
      syndrome (RR, 5.23; 95% CI, 2.82-9.69). There was no statistically significant
      increased risk of stillbirth (RR, 1.51; 95% CI, 0.94-2.40) or neonatal death (RR,
      1.26; CI, 0.77-2.06). Children of women with schizophrenia had a marginally
      statistically significant increase in the risk of congenital malformations (RR,
      1.70; 95% CI, 1.04-2.77). CONCLUSIONS: Children of women with schizophrenia have
      a considerable increased risk of death caused by sudden infant death syndrome.
      However, the results should be interpreted in the light of failure to adjust for
      socioeconomic status, substance abuse, smoking status, and psychotropic
      medication use.

PMID- 11448376
TI  - Early coadministration of clonazepam with sertraline for panic disorder.
AB  - BACKGROUND: There is debate about combining benzodiazepines with selective
      serotonin reuptake inhibitors in the acute treatment of panic disorder. Although
      this medication combination is widely used in clinical practice, there is no well
      tested, optimal method of coadministering these medications for the treatment of
      panic disorder. The purpose of this study was to test the efficacy of early
      coadministration of clonazepam with sertraline in the treatment of panic
      disorder. METHODS: Fifty patients with panic disorder were randomized into a
      double-blind clinical trial. Patients received open-label sertraline for 12 weeks
      (target dose, 100 mg/d), and in addition were randomized to groups receiving
      either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the
      first 4 weeks of the trial. The clonazepam dose was then tapered during 3 weeks
      and discontinued. RESULTS: Thirty-four (68%) of 50 patients completed the trial.
      Drop-out rates were similar in the sertraline/placebo vs the
      sertraline/clonazepam group (38% vs 25%) (P =.5). An intent-to-treat analysis (on
      last observation carried forward data) revealed a much greater proportion of
      responders in the sertraline/clonazepam compared with the sertraline/placebo
      group at the end of week 1 of the trial (41% vs 4%) (P =.003). There was also a
      significant between-group difference at the end of week 3 with 14 (63%) of 22 of
      the sertraline/clonazepam group responding to treatment vs 8 (32%) of 25 of the
      sertraline/placebo group (P =.05). This difference was not observed at other
      times during the trial. CONCLUSION: These data indicate that rapid stabilization
      of panic symptoms can be safely achieved with a sertraline/clonazepam
      combination, supporting the clinical utility of this type of regimen for
      facilitating early improvement of panic symptoms relative to sertraline alone.

PMID- 11448377
TI  - An evaluation of drug treatments for adolescents in 4 US cities.
AB  - BACKGROUND: Little is known about outcomes of community-based treatment programs
      for adolescents with drug problems. METHODS: We studied 1167 adolescents (age
      range, 11-18 years; 368 females, 799 males) from 4 US cities (Pittsburgh, Pa;
      Minneapolis, Minn; Chicago, Ill; and Portland, Ore) using a naturalistic,
      nonexperimental evaluation design. These adolescents were consecutive admissions
      during the period from 1993 to 1995 at 23 community-based treatment programs in
      the Drug Abuse Treatment Outcome Studies for Adolescents. Included were 418
      admissions to 8 residential programs, 292 admissions to 9 outpatient drug-free
      programs, and 457 admissions to 6 short-term inpatient programs. RESULTS:
      Adolescents in treatment typically had multiple problems (eg, 58.4% of them were
      involved in the legal system, and 63.0% met diagnostic criteria for a mental
      disorder). Nevertheless, less than half (43.8%) of all patients reported weekly
      marijuana use in the year following treatment (dropping from 80.4% in the year
      before admission). Similarly, there were decreases in heavy drinking (dropping
      from 33.8% to 20.3%), use of other illicit drugs (dropping from 48.0% to 42.2%),
      and criminal involvement (dropping from 75.6% to 52.8%). Additionally, patients
      reported better psychological adjustment and school performance after treatment.
      Longer stays in treatment were positively associated with several favorable
      outcomes, although length of time in treatment was generally short. CONCLUSIONS:
      Substance abuse treatment for adolescents is effective in achieving many
      important behavioral and psychological improvements. Strategies specific to
      adolescents to improve their treatment retention and completion are needed to
      maximize the therapeutic benefits of drug treatment.

PMID- 11448378
TI  - Long-term effectiveness of disseminating quality improvement for depression in
      primary care.
AB  - BACKGROUND: This article addresses whether dissemination of short-term quality
      improvement (QI) interventions for depression to primary care practices improves
      patients' clinical outcomes and health-related quality of life (HRQOL) over 2
      years, relative to usual care (UC). METHODS: The sample included 1299 patients
      with current depressive symptoms and 12-month, lifetime, or no depressive
      disorder from 46 primary care practices in 6 managed care organizations. Clinics
      were randomized to UC or 1 of 2 QI programs that included training local experts
      and nurse specialists to provide clinician and patient education, assessment, and
      treatment planning, plus either nurse care managers for medication follow-up (QI
      meds) or access to trained psychotherapists (QI-therapy). Outcomes were assessed
      every 6 months for 2 years. RESULTS: For most outcomes, differences between
      intervention and UC patients were not sustained for the full 2 years. However, QI
      therapy reduced overall poor outcomes compared with UC by about 8 percentage
      points throughout 2 years, and by 10 percentage points compared with QI-meds at
      24 months. Both interventions improved patients' clinical and role outcomes,
      relative to UC, over 12 months (eg, a 10-11 and 6-7 percentage point difference
      in probable depression at 6 and 12 months, respectively). CONCLUSIONS: While most
      outcome improvements were not sustained over the full 2 study years, findings
      suggest that flexible dissemination of short-term, QI programs in managed primary
      care can improve patient outcomes well after program termination. Models that
      support integrated psychotherapy and medication-based treatment strategies in
      primary care have the potential for relatively long-term patient benefits.

PMID- 11448379
TI  - Continuing treatment with novel antipsychotic drugs despite leukopenia or
      thrombocytopenia.

PMID- 11448380
TI  - Clinical significance of esophageal histologic findings after antireflux surgery.
AB  - HYPOTHESIS: Only limited and controversial information exists regarding the
      histologic effect of successful antireflux surgery on esophageal mucosa and its
      clinical significance. DESIGN AND SETTINGS: A randomized, blinded follow-up study
      conducted in a university hospital between January 1, 1992, and December 31,
      1997, with a mean follow-up of 8 months. PATIENTS: Forty patients with severe
      symptomatic gastroesophageal reflux disease (24 men and 16 women; mean age, 50
      years). MAIN OUTCOME MEASURES: Microscopic signs and severity of esophagitis
      analyzed by 2 blinded histopathologists. RESULTS: Histopathologist 1 interpreted
      22 (69%) of 32 postoperative biopsy specimens as normal; 7 (22%), as showing mild
      changes; 1 (3%), moderate changes; and 2 (6%), severe changes of reflux
      esophagitis. Histopathologist 2 interpreted 25 (78%) of 32 postoperative biopsy
      specimens as normal (P =.001); 1 (3%), as showing mild changes (P =.003); 4
      (13%), moderate changes; and 2 (6%), severe changes. Between histopathologist 1
      (90.6%) and histopathologist 2 (81%), the absence of esophageal mucosal
      inflammation correlated best with normalized pH monitoring. CONCLUSIONS: These
      findings suggest that, if other findings such as those from fundic wrap at
      endoscopy and 24-hour pH monitoring are normal, the clinical significance of
      routine esophageal histologic examination after successful fundoplication is
      limited.

PMID- 11448381
TI  - Long-term survival following induction chemoradiotherapy and esophagectomy for
      esophageal carcinoma.
AB  - HYPOTHESIS: Long-term survival is rare in patients treated for esophageal
      carcinoma. Several clinical trials suggest the possibility of prolonged survival
      in patients who undergo induction chemoradiotherapy plus esophagectomy. DESIGN:
      Prospective uncontrolled study. SETTING: University hospital. PATIENTS AND
      METHODS: Forty-four patients with carcinoma of the esophagus or gastroesophageal
      junction were prospectively entered into a phase II trial of preoperative 5
      fluorouracil, cisplatin, and interferon alfa with concurrent external beam
      radiotherapy before esophagectomy. Curative resection was performed on 36 of 41
      patients who completed the induction chemoradiotherapy. RESULTS: Of the 44
      patients, 17 are alive at a median follow-up of 50 months. Of these 17 patients,
      15 show no evidence of recurrent disease. Of the 14 patients with long-term
      survival (> or =3 years), 1 patient died of disease, and another patient is alive
      with disease. The remaining 12 patients are alive and disease-free (median follow
      up, 54 months). Six patients have survived longer than 4 years and 3 patients
      longer than 5 years. Subsequent primary tumors have developed in 2 patients. One
      patient had a recurrence at 11 months following initiation of treatment and
      remains disease-free 43 months postresection of a single brain metastasis.
      Standard clinicopathologic parameters (age, sex, histologic findings,
      chemoradiotherapy regimen, and clinical and pathologic stages) were not
      significantly associated with a survival time of 3 years or longer (Fisher exact
      test, 2-tailed). Although not significant, p 53 mutational status suggested long
      term survival. In 11 of 14 patients who are alive with no history of recurrence,
      p53 genotyping demonstrated no point mutations in 10 patients. Median survival
      time for the long-term survivors has not been reached. CONCLUSIONS: Long-term
      survival can be achieved in patients with esophageal carcinoma who undergo
      induction chemoradiotherapy and esophagectomy. Recurrence is unlikely in patients
      who survive for 3 years or longer after undergoing this multimodality treatment.

PMID- 11448383
TI  - A prospective randomized trial of laparoscopic Nissen fundoplication with
      anterior vs posterior hiatal repair.
AB  - HYPOTHESIS: The technique used for repair of the esophageal hiatus during
      laparoscopic Nissen fundoplication can influence the likelihood of postoperative
      dysphagia. DESIGN: A prospective double-blind randomized control trial. SETTING:
      A university teaching hospital. PARTICIPANTS: A total of 102 patients with proven
      gastroesophageal reflux disease, undergoing a laparoscopic Nissen fundoplication
      were randomized to undergo fundoplication with either anterior (47 patients) or
      posterior (55 patients) repair of the diaphragmatic hiatus. Patients were
      excluded for the following reasons: they had esophageal motility disorders,
      required a concurrent abdominal procedure, had undergone previous antireflux
      surgery, or had very large hiatus hernias. INTERVENTIONS: Laparoscopic Nissen
      fundoplication with anterior vs posterior hiatal repair. MAIN OUTCOME MEASURES:
      Independent assessment of dysphagia, heartburn, patient satisfaction, and other
      symptoms 1, 3, and 6 months following surgery, using multiple standardized
      clinical grading systems. Objective measurement of lower esophageal sphincter
      pressure, esophageal emptying time, distal esophageal acid exposure, and
      endoscopic assessment of postoperative anatomy and esophageal mucosa. RESULTS:
      Symptoms of postoperative dysphagia, relief of heartburn, and overall
      satisfaction 6 months after surgery were not influenced by the hiatal repair
      technique. However, to achieve a similar incidence of dysphagia, more patients
      who initially underwent posterior hiatal repair required a second surgical
      procedure (6 vs 0 patients). The hiatal repair technique did not affect the
      likelihood of early postoperative paraesophageal herniation. CONCLUSION: Anterior
      suturing of the hiatus appears to be at least as good in the short-term as
      posterior suturing as a method of narrowing the hiatus during laparoscopic Nissen
      fundoplication.

PMID- 11448384
TI  - Reducing overtriage without compromising outcomes in trauma patients.
AB  - HYPOTHESIS: Changing category 1 criteria to include primarily physiologic and
      anatomic indicators of injury, eliminating mechanism of injury criteria,
      decreases the rate of overtriage without compromising outcomes. METHODS:
      Retrospective review of our American College of Surgeons-verified level I trauma
      registry from January 1, 1996, to December 31, 1998, comparing patients before
      and after trauma alert criteria changes. RESULTS: There was a significant
      decrease in category 1 alerts, representing a reduction in overtriage. There was
      a concomitant increase in injury severity and mortality in category 1 patients.
      There was no significant change in injury severity or mortality for category 2
      patients. CONCLUSIONS: There was a significant reduction in overtriage of trauma
      patients demonstrated without an appreciable impact on patient outcome. Changing
      trauma response criteria to more physiologic and anatomic indicators allowed
      improved triage of trauma patients, which improves resource allocation.

PMID- 11448385
TI  - Prophylactic excision of the gallbladder and bile duct for patients with
      pancreaticobiliary maljunction.
AB  - HYPOTHESIS: Pancreaticobiliary maljunction (PBM) is a high-risk factor for
      biliary tract carcinogenesis because of a continuous reflux of pancreatic juice
      into the biliary tract. It remains to be disclosed whether we should perform
      prophylactic excision of gallbladders and bile ducts. DESIGN: A person-year
      method. SETTING: A university hospital. PATIENTS: We studied 68 patients with PBM
      treated between August 1, 1974, and December 31, 1999. MAIN OUTCOME MEASURES:
      Relative risks (observed number-expected number ratios) of gallbladder and bile
      duct carcinomas according to type of bile duct dilation (ie, cystic dilation,
      diffuse dilation, and nondilation). RESULTS: Observed number-expected number
      ratios of gallbladder carcinomas were high: 291.3 in 43 patients with cystic
      dilation, 167.2 in 16 patients with diffuse dilation, and 419.6 in 7 patients
      with nondilation. Observed number-expected number ratios of bile duct carcinomas
      were 194.2 in 43 patients with cystic dilation before surgery and 142.8 in 39
      patients with cystic dilation after long postsurgical follow-up. All these values
      were statistically significant (P<.01). CONCLUSIONS: The gallbladder carries a
      high risk for carcinogenesis in all types of dilation in patients with PBM. The
      bile duct carcinomas of PBM were exclusively identified by the type of cystic
      dilation. Prophylactic cholecystectomy should be recommended for all dilation
      types, and prophylactic excision of bile ducts including cholecystectomy should
      be performed in patients with PBM and cystic dilation. Complete excision of
      extrahepatic dilated bile ducts and careful follow-up for carcinogenesis in
      residual dilated bile ducts should be recommended for patients with PBM and
      cystic dilation.

PMID- 11448387
TI  - A new concept of a multidisciplinary wound healing center and a national expert
      function of wound healing.
AB  - HYPOTHESIS: An independent, multidisciplinary wound healing center in an accepted
      national expert function of wound healing is the optimal way to improve
      prophylaxis and treatment of patients with problem wounds. DESIGN: A clinical
      perspective analysis. SETTING: An independent, multidisciplinary wound healing
      center focusing on all types of problem wounds, organized as a university
      hospital department, and integrated in an expert function in the national health
      care organization of Denmark. PATIENTS AND METHODS: Patients with all types of
      problem wounds referred to and treated in the center during the first years of
      its existence provided a model for a new multidisciplinary structure for
      treatment of wound patients in the health care system. RESULTS: During the first
      3 years of the fully functioning wound healing center, a total of 23 802 patient
      consultations were performed in the outpatient clinic, and 1014 patients with
      problem wounds were hospitalized in the inpatient ward. The surgical concept of
      the center has resulted in improved healing rates in patients with leg ulcers and
      decreased rates of major amputations. The outpatient function has resulted in a
      decrease in the number of patients transported in beds to the center. This
      structure provides better opportunities for basic and clinical research as well
      as for establishing expert education for all types of health care personnel. The
      center's structure has been the background for establishing an expert function in
      wound healing, allowing the wound healing area area to be fully integrated in the
      Danish National Health Care System. Overall, the concept and structure of the
      center have enhanced the knowledge and understanding of wound problems and
      increased the status of wound healing and patient care. CONCLUSIONS: Establishing
      multidisciplinary centers integrated into an accepted national expert function of
      wound healing is an optimal way to improve the clinical outcome of prophylaxis
      and treatment of all types of problem wounds. This model, with minor adjustments,
      may be applicable for both industrialized and developing countries.

PMID- 11448388
TI  - Surgical palliation at a cancer center: incidence and outcomes.
AB  - HYPOTHESIS: Surgical intervention in palliative care is common; however, the
      indications, risks, and outcomes are not well described. DESIGN: Retrospective
      review of surgical cases during a 1-year period with a minimum 1-year survival
      update. SETTING: A National Cancer Institute-designated comprehensive cancer
      center. PATIENTS: Patients with a cancer diagnosis undergoing operative
      procedures. MAIN OUTCOME MEASURES: Number of palliative surgeries and analysis of
      length of stay, morbidity, and mortality. RESULTS: Palliative surgeries comprised
      240 (12.5%) of 1915 surgical procedures. There were 170 major and 70 minor
      procedures. Neurosurgical (46.0%), orthopedic (31.3%), and thoracic (21.5%)
      surgical procedures were frequently palliative. The most common primary diagnoses
      were lung, colorectal, breast, and prostate cancers. Length of hospital stay was
      12.4 days (range, 0-99 days), with 21.3% of procedures performed on an outpatient
      basis. The 30-day mortality was 12.2%, with 5 patients dying within 5 days of
      their procedure. The overall mortality was 23.3% (56/240). Mortality for surgical
      procedures classified as major was 21.9% (44/170) and 10.0% (7/70) for those
      classified as minor (Fisher exact test, P<.01). CONCLUSIONS: Significant numbers
      of palliative procedures are performed at our cancer center. Overall morbidity
      and mortality were high; however, a significant number of patients had short
      hospital stays and low morbidity. Palliative surgery should remain an important
      part of end-of-life care. Patients and their families must be aware of the high
      risks and understand the clear objectives of these procedures.

PMID- 11448390
TI  - Role of axillary node dissection in patients with T1a and T1b breast cancer: Mayo
      Clinic experience.
AB  - HYPOTHESIS: The incidence of nodal positivity in patients with early breast
      cancer is low, and axillary lymph node dissection may not be justified in all
      such patients. DESIGN: Retrospective case series. SETTING: Tertiary institution.
      PATIENTS: All patients with T1a and T1b breast cancer who had both primary breast
      surgery and axillary lymph node dissection at Mayo Clinic in Jacksonville, Fla,
      from January 1, 1992, through February 28, 1998. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Tumor size and biological grade, estrogen and progesterone
      receptor status, number of nodes harvested, and number of nodes positive for
      disease. RESULTS: Of 163 patients studied, 39 had T1a and 124 had T1b tumors.
      Node positivity was 0% for T1a and 11.3% for T1b tumors (P =.03). Lymph node
      involvement and estrogen receptor status were not related (P =.29). However, the
      risk of lymph node positivity for progesterone receptor-negative (P =.01) and
      estrogen receptor-negative/progesterone receptor-negative tumors was
      significantly higher than for progesterone and estrogen/progesterone receptor
      positive tumors (P =.04). Furthermore, the risk of lymph node positivity was
      significantly higher as tumor size increased (P =.002). Finally, higher tumor
      grade conferred a higher risk of lymph node involvement (P =.02). CONCLUSIONS:
      T1a tumors have minimal risk of nodal positivity and may not require subsequent
      axillary lymph node dissection in the future. T1b tumors should be managed with
      routine analysis of axillary lymph node status. Whether sentinel node mapping can
      change this standard awaits further study.

PMID- 11448391
TI  - Transxiphoid bilateral palpation in video-assisted thoracoscopic lung
      metastasectomy.
AB  - OBJECTIVE: To evaluate indications, limits, and merits of transxiphoid bilateral
      palpation during video-assisted thoracoscopy (VAT) lung metastasectomy. DESIGN:
      Survey retrospective study with a minimum follow-up of 1 year. SETTING:
      University hospital. PATIENTS: From December 1995 to September 1999, 29 of 45
      patients operated on for pulmonary metastasectomy were approached through a
      transxiphoid VAT. Primary sites were colon-rectum (n = 13), kidney (n = 4), limb
      osteosarcoma (n = 3), uterus (n = 2), larynx (n = 2), breast (n = 1), skin
      melanoma (n = 1), prostate gland (n = 1), back fibrosarcoma (n = 1), and ovary (n
      = 1). Bilateral palpation was performed in 23 patients, although only 10 had
      radiological evidence of bilateral disease. RESULTS: No perioperative or 30-days
      postoperative mortality was recorded. Acute and chronic pain was similar to that
      of other VATs and significantly less than sternotomy. Mean +/- SD chest-drain
      time and hospital stay were 2.8 +/- 1.19 days and 4.3 +/- 1.78 days,
      respectively. Sixty-nine lesions, 60 of them metastatic, were resected by laser
      (n = 29) or stapler (n = 40). Bilateral exploration permitted the discovery of 15
      radiologically undetected lesions, 11 of which were found to be malignant.
      Contralateral metastases were found in 5 patients predicted to have unilateral
      disease. Mean +/- SD follow-up was 22.89 +/- 10.87 months (range, 9-60 months).
      Six patients developed new pulmonary metastases after a mean interval of 13.6
      months; 3 of these patients relapsed in the unexplored hemithorax after 6, 9, and
      12 months, respectively. CONCLUSIONS: The use of the transxiphoid VAT approach
      was safe, applicable in many instances, and effective in detecting occult
      metastases by manual bilateral palpation. The advantages of a VAT procedure can
      be coupled with those provided by a radical operation.

PMID- 11448392
TI  - The laparoscopic approach to abdominal hydatid cysts: a prospective nonselective
      study using the isolated hypobaric technique.
AB  - HYPOTHESIS: The laparoscopic isolated hypobaric technique that we developed and
      use is safe and feasible for almost all kinds of hepatic and extrahepatic
      abdominal hydatid cysts. DESIGN: A case series. PATIENTS: Between August 1992 and
      December 1999, 31 patients with no selection criteria underwent 32 consecutive
      laparoscopic operations for 52 symptomatic hydatid cysts located in the liver
      (49), spleen (1), and pelvis (2). Eleven patients underwent surgery for between 2
      to 5 cysts. INTERVENTIONS: The main surgical maneuvers (puncture, parasite
      neutralization, and complete evacuation) were performed through an assembled
      transparent cannula, in which a vacuum was created, while its tip adhered firmly
      to the cyst wall. Following evacuation of the cyst contents, we attempted to
      perform partial pericystectomy, omentoplasty, and closed-suction drainage. MAIN
      OUTCOME MEASURES: Surgical complications and postoperative disease recurrence.
      RESULTS: Mean cyst diameter was 8.4 cm (range, 3.5-25 cm). Seven cysts were
      subdiaphragmatic, and 6 were on the posterior (hidden) aspect of the liver. Mean
      postoperative follow-up was 49 months. Forty-one cysts contained live parasites,
      and 11 were secondarily infected. Twenty-four cysts were complex. Perioperative
      complications occurred in 5 patients, including 1 patient who died 1 month after
      surgery owing to Candida sepsis. Mean hospital stay was 6 days. No evidence of
      recurrence was recorded during follow-up. CONCLUSIONS: The isolated hypobaric
      laparoscopic technique described provides a safe and efficacious approach to
      almost all types of abdominal hydatid cysts and takes advantage of the recognized
      benefits of the laparoscopic approach.

PMID- 11448393
TI  - Negative results of randomized clinical trials published in the surgical
      literature: equivalency or error?
AB  - HYPOTHESIS: We hypothesized that review of randomized controlled clinical trials
      (RCTs) with nonstatistically significant or "negative" results published in the
      surgical literature do not have appropriate statistical power to demonstrate
      equivalency between treatment arms. DATA SOURCES AND STUDY SELECTION: The MEDLINE
      database was searched to obtain reports of all RCTs with negative results
      published in 3 surgical journals from 1988 to 1998. Manual review of one year
      (1997) of publications for each journal was performed to validate our search
      strategy. Equivalency was evaluated using the Two One-Sided Tests Procedure and
      post hoc power calculations. DATA SYNTHESIS: Ninety reports of RCTs with negative
      results were identified in the surgical literature between 1988 and 1998. The
      manual review of 1997 showed a 100% retrieval rate for our search strategy. After
      applying the Two One-Sided Tests Procedure, 35 reports (39%) met the criteria for
      demonstrating equivalency. The other 55 reports (61%) contained at least a 10%
      absolute difference in the 90% confidence interval of Delta. Using the power
      calculation method, only 22 (24%) articles had a power greater than.80 to detect
      a 50% difference in therapeutic effect. Only 29% of the reports included a formal
      sample size calculation and these studies were more likely to demonstrate
      equivalency than those without a sample size estimate (P<.01). CONCLUSIONS: Many
      reports from negative RCTs published in the surgical literature lack sufficient
      statistical power to establish that clinically important differences are not
      present. Surgeons should perform appropriate sample size calculations when
      designing RCTs and recognize the utility of confidence intervals when reporting
      negative results.

PMID- 11448394
TI  - Prospective study comparing wounds closed with tape with sutured wounds in
      colorectal surgery.
AB  - HYPOTHESIS: To test the efficacy of adhesive paper tape in the closure of clean
      contaminated wounds following elective colorectal resection. DESIGN: A
      prospective, nonrandomized controlled study. SETTING: A medical center that
      offers a mixture of primary, secondary, and tertiary care services. PATIENTS: The
      group undergoing skin closure with paper tape (PT group) consisted of 150
      patients. The group undergoing skin closure with interrupted suture (IS group)
      also comprised 150 patients. All 300 patients underwent elective colorectal
      resection in 1997. MAIN OUTCOME MEASURES: The duration of skin closure, wound
      complication rate, and cosmetic appearance of the scar at 6 months after
      operation were compared using the chi(2)test or t test. RESULTS: The mean +/- SD
      average duration of skin closure was 116 +/- 23 seconds for the PT group and 457
      +/- 64 seconds for the IS group (P<.01). The wound complication rate was 3.3% (3
      cases with wound infection; 2 with wound separation) for the PT group and 3.3% (5
      cases with wound infection) for the IS group (P = 1.0). No significant
      differences were found between the narrowest width (mean +/- SD, 2.2 +/- 0.9 mm
      vs 2.3 +/- 1.0 mm) and widest width (mean +/- SD, 4.7 +/- 2.0 mm vs 4.3 +/- 1.8
      mm) of scar formation between the 2 groups at 6 months after the operation.
      Ninety-eight percent of patients in the PT group reported satisfaction with their
      scar, compared with 92% in the IS group (P =.03). CONCLUSION: Compared with the
      traditional suture method, paper tape closure in the treatment of clean
      contaminated wounds was less time consuming and produced greater patient
      satisfaction with no increased rate of wound complications.

PMID- 11448395
TI  - Macrophage effector mechanisms in melanoma in an experimental study.
AB  - BACKGROUND: The tumor-bearing state is known to induce immune dysfunction that
      contributes to increased infectious complications and tumor progression. However,
      the mechanisms underlying this immunosuppression remain unclear. HYPOTHESIS:
      Macrophage (MO) dysfunction may play a role in tumor-induced immunosuppression.
      DESIGN AND MAIN OUTCOME MEASURES: Using a murine model, this study investigated
      the effects of melanoma growth on peritoneal macrophage effector molecule and
      prostaglandin production, MO-mediated cytotoxicity, and candidacidal mechanisms.
      Female C57BL/6 mice were inoculated with 106 B16 melanoma cells or a salt
      solution subcutaneously. Mice were euthanized 3 weeks later and peritoneal MOs
      were harvested and assayed for nitric oxide, superoxide anion, tumor necrosis
      factor alpha, and prostaglandin E(2)production. Macrophage-mediated cytotoxicity
      against B16 melanoma targets and MO candidacidal mechanisms were also measured.
      RESULTS: Macrophage production of nitric oxide, superoxide anion, and tumor
      necrosis factor alpha were significantly decreased, while prostaglandin
      E(2)production was increased in MOs from melanoma-bearing mice. Concomitantly, MO
      mediated cytotoxicity and candidacidal mechanisms were significantly impaired.
      CONCLUSIONS: Melanoma growth leads to decreased MO effector molecule production,
      increased prostaglandin E(2)production, and impaired MO cytotoxic and
      candidacidal mechanisms. These results may help explain the observed increased
      infectious complications in the tumor-bearing host. Strategies aimed at restoring
      MO function may have therapeutic potential.

PMID- 11448396
TI  - Minimally invasive open parathyroidectomy in an endemic goiter area: a
      prospective study.
AB  - HYPOTHESIS: Single-gland disease identified by preoperative localization studies
      in combination with rapid intraoperative parathyroid hormone monitoring seems to
      allow a limited exploration of the neck in sporadic primary hyperparathyroidism.
      Minimally invasive open parathyroidectomy by lateral approach (oMIP) in sporadic
      primary hyperparathyroidism seems feasible in an endemic goiter region. DESIGN:
      One hundred consecutive patients with sporadic primary hyperparathyroidism
      underwent preoperative double-phase technetium Tc 99m sestamibi scanning with
      single-photon emission computed tomography and high-resolution ultrasonography
      with color Doppler imaging of the cervical region. All patients were operated on
      with the use of quick parathyroid hormone assay to confirm the surgical success
      "on-line." Patients with localized single-gland disease, irrespective of
      additional ipsilateral thyroid disease requiring surgery, were selected for oMIP.
      Success of the preoperative localization studies, postoperative (at least 6
      months) serum calcium levels, and operating time were analyzed. SETTING:
      University hospital, section of endocrine surgery. RESULTS: Of 100 patients, 83
      (83%) were considered suitable for oMIP. In 69 patients, oMIP was finished
      successfully. Nine of these had had previous neck surgery, and another 24
      underwent additional ipsilateral thyroid resection. Permanent normocalcemia was
      achieved in 67 (97.1%) of 69 patients and 98 (98%) of 100 patients. CONCLUSION:
      The oMIP in combination with quick parathyroid hormone assay may become the
      treatment of choice for sporadic primary hyperparathyroidism in an endemic goiter
      region in centers with high experience in thyroid and parathyroid surgery. It
      allows treatment of concomitant ipsilateral thyroid disease and is feasible in
      reoperations.

PMID- 11448397
TI  - Experimental short-term immunosuppression after bowel transplantation and donor
      specific bone marrow infusion.
AB  - HYPOTHESIS: We previously showed in a large animal pig model that unmodified
      donor-specific bone marrow infusion (DSBMI) did not facilitate total bowel
      engraftment; in contrast, it increased the risks of rejection, infection, and
      graft-vs-host disease (GVHD) posttransplant. We hypothesize that continuous
      immunosuppression, in combination with DSBMI, might contribute to-or even trigger
      these unwarranted immune responses by both host and graft; therefore,
      discontinuing immunosuppression might decrease these risks and prolong survival.
      METHODS: Six groups of outbred, mixed lymphocyte culture-reactive pigs underwent
      a total (small and large) bowel transplant: group 1, nonimmunosuppressed control
      pigs (n = 5); group 2, nonimmunosuppressed DSBMI pigs (n = 6); group 3,
      tacrolimus (indefinite) pigs (n = 7); group 4, tacrolimus (indefinite) plus DSBMI
      pigs (n = 7); group 5, tacrolimus (10 days only) pigs (n = 5); and group 6,
      tacrolimus (10 days only) plus DSBMI pigs (n = 6). RESULTS: The combination of
      short-term immunosuppression and DSBMI (group 6) significantly prolonged
      survival, compared with short-term immunosuppression only (group 5) or DSBMI only
      (group 2). Short-term immunosuppression and DSBMI (group 6) did not prolong
      overall survival, compared with indefinite immunosuppression with (group 4) or
      without (group 3) DSBMI: survival rates at 7, 14, and 28 days posttransplant were
      100%, 100%, and 67% in group 6; 100%, 100%, and 71% in group 3; and 100%, 67%,
      and 47% in group 4 (P =.14). Short-term immunosuppression and DSBMI (group 6)
      increased the incidence of rejection, infection, and GVHD, compared with
      indefinite immunosuppression without (but not with) DSBMI. CONCLUSIONS: Short
      term immunosuppression and DSBMI did not prolong survival and did not reduce the
      incidence of death from rejection, infection, or GVHD, compared with indefinite
      immunosuppression without DSBMI. But short-term immunosuppression and DSBMI
      resulted in a lower incidence of death from infection and GVHD, compared with
      indefinite immunosuppression and DSBMI. When immunosuppression was discontinued
      10 days posttransplant, the effect of DSBMI was insufficient to avert death from
      rejection. CLINICAL RELEVANCE: The clinical results of bowel transplantation
      trail those of other solid organ transplants. It reduced the rates of infection
      and GVHD. Our study shows that systemically infused donor-specific bone marrow
      with short-term or indefinite immunosuppression does not improve outcome after
      bowel transplantation. It seems necessary to modify the time, dosing, routing,
      and/or composition of donor-specific bone marrow before it can be successfully
      used in clinical bowel transplantation.

PMID- 11448398
TI  - Arterial PCO2 and cardiovascular function during endoscopic neck surgery with
      carbon dioxide insufflation.
AB  - BACKGROUND: Endoscopic parathyroidectomy and thyroidectomy were introduced into
      clinical practice in 1995. Concerns about the use of carbon dioxide insufflation
      in the neck exist owing to reports of potential adverse metabolic and hemodynamic
      changes. HYPOTHESIS: Carbon dioxide insufflation in the neck may cause adverse
      effects on hemodynamic and blood gas levels. These adverse effects may reflect
      the level of pressure and duration of insufflation. METHODS: Fifteen pigs, 5 per
      group, underwent endoscopic thyroidectomy at 10, 15, and 20 mm Hg. Partial
      pressure of carbon dioxide (arterial), pH, cardiac output, central venous
      pressure, heart rate, and mean arterial pressure (MAP) were measured at baseline,
      1 and 2 hours after carbon dioxide insufflation, and 30 minutes after
      desufflation. RESULTS: At 10 mm Hg, PaCO2 increased slightly but not
      significantly, and neither acidosis nor adverse hemodynamic changes were
      observed. Hypercarbia, moderate acidosis, and a slight increase in MAP occurred
      in pigs undergoing surgery at 15 mm Hg (MAP increased to 88 +/- 2.4 mm Hg from a
      baseline value of 78 +/- 3.53 mm Hg; P<.05). Pigs undergoing surgery at 20 mm Hg
      experienced severe hypercarbia and acidosis, as well as a significant decrease in
      MAP (P<.05). Central venous pressure decreased at 1 hour (P<.05) and increased at
      2 hours (P<.05) in pigs undergoing surgery at 15 and 20 mm Hg. After
      desufflation, PaCO2 and pH levels were normal for the 10 and 15 mm Hg groups,
      while pigs undergoing surgery at 20 mm Hg developed a higher degree of
      hypercarbia and acidosis (P =.001). CONCLUSIONS: Carbon dioxide neck insufflation
      is safe at 10 mm Hg. The use of insufflation pressures higher than 15 mm Hg
      should be avoided due to the potential risk for metabolic and hemodynamic
      complications.

PMID- 11448399
TI  - Blood supply of hemipelvectomy flaps: the anterior flap hemipelvectomy.
AB  - In posterior flap hemipelvectomy, preservation of the gluteus maximus with the
      flap guarantees its viability regardless of the level of ligation of the iliac
      vessels. In anterior flap hemipelvectomy with the quadriceps femoris attached to
      the flap, the dominant blood supply is through the lateral femoral circumflex
      branches of the profunda vessels, which is sufficient to maintain the flap.

PMID- 11448401
TI  - Special feature: Image of the month. Cecal bascule.

PMID- 11448402
TI  - Moments in surgical history: James Thacher and his military journal during the
      American Revolutionary War.

PMID- 11448403
TI  - Incremental prognostic value of technetium-99m-tetrofosmin exercise myocardial
      perfusion imaging for predicting outcomes in patients with suspected or known
      coronary artery disease.
AB  - Technetium-99m (Tc-99m)-tetrofosmin is a radio isotope that has been shown to be
      an accurate alternative to thallium-201 for detecting coronary artery disease.
      However, its prognostic value is less well determined. To this end, 459
      consecutive patients (mean age 58 +/- 10 years) with suspected or known coronary
      artery disease underwent exercise single-photon emission tomography Tc-99m
      tetrofosmin scintigraphy. Follow-up, defined as the time from scanning until a
      soft event (revascularization procedures), a hard event (myocardial infarction
      and cardiac death), or patient response, lasted up to 78 months (median 38). An
      ischemic scintigraphic perfusion score, which takes into account both the extent
      and severity of reversible perfusion defects, was calculated to estimate the
      severity of perfusion abnormalities. Patients with normal scans were at low risk
      of events (yearly hard event rate 0.5% and soft event rate 0.9%). The rate of
      outcomes increased significantly with abnormal scans (yearly hard event rate 4.9%
      and soft event rate 10.3%). Statistical analysis using the Kaplan-Meyer survival
      curves showed a significant difference in event-free survival between patients
      with normal and abnormal scans. With use of Cox proportional-hazards analysis,
      after adjusting for prescan information, nuclear data provided incremental
      prognostic value for hard events (clinical and exercise data vs nuclear data; chi
      square = 15.5 vs 33.4, p <0.001). Exercise single-photon emission tomographic
      scintigraphy using Tc-99m-tetrofosmin provides significant independent
      information on the subsequent risk of hard and soft events. The annual event rate
      for hard and soft events is <1% for patients with a normal scan. Furthermore,
      this tracer yields incremental prognostic information in addition to that
      provided by clinical and exercise data for hard events.

PMID- 11448404
TI  - Age and the utilization of cardiac catheterization following uncomplicated first
      acute myocardial infarction treated with thrombolytic therapy (The Second
      National Registry of Myocardial Infarction [NRMI-2]).
AB  - Considerable data indicates that patients <50 years of age have lower morbidity
      and mortality after acute myocardial infarction (AMI) than older patients. It has
      been demonstrated that use of routine cardiac catheterization and
      revascularization in younger patients with AMI and successful thrombolysis does
      not confer benefit compared with a more conservative approach. Despite this, it
      has been our impression that cardiac catheterization is frequently employed in
      younger patients with AMI. Patients with uncomplicated initial AMI treated with
      thrombolytic therapy in the Second National Registry of Myocardial Infarction
      (NRMI-2) between June 1994 and April 1998 were identified. Patients were
      categorized into 4 age strata for purposes of analysis. A total of 61,232 cases
      met our inclusion criteria. Cardiac catheterization was performed during
      hospitalization in 78% of patients after an uncomplicated initial AMI. Age was
      inversely associated with receipt of cardiac catheterization: 85% of those < or
      =49 years old underwent catheterization compared with 63% of those > or =70 years
      old. Regression analysis revealed that use of catheterization was 2.9 times
      greater (95% confidence intervals 2.7 to 3.2) in patients < or =49 years old
      compared with those > or =70 years old. Geographic location and payor status also
      strongly influenced utilization of this procedure. In conclusion, routine
      coronary angiography after uncomplicated AMI is extensively utilized in all age
      groups, particularly in those <50 years of age. The efficacy and cost
      effectiveness of this strategy in these patients has not yet been determined in
      clinical trials.

PMID- 11448405
TI  - Association of C-reactive protein with markers of prevalent atherosclerotic
      disease.
AB  - Recent prospective studies have demonstrated that elevated C-reactive protein
      (CRP) is a marker of increased risk of atherothrombotic clinical events. We
      examined in a large, cross-sectional family-based study (n = 875 men, 948 women)
      whether serum CRP was associated with prevalent coronary heart disease (CHD), the
      ankle/brachial blood pressure index, or carotid intima-media thickness, an
      indicator of subclinical atherosclerosis as assessed by B-mode ultrasound. CRP
      was associated with many other cardiovascular risk factors, particularly markers
      of obesity and insulin resistance, markers of inflammation and acute phase
      reaction, and hormone replacement therapy. Adjusted for age and family type,
      there was a weak positive association of CRP with carotid intima-media thickness
      in both genders and with prevalent CHD in women. However, adjustment for other
      risk factors completely eliminated the associations. For example, among women,
      the risk factor-adjusted mean values of intima-media thickness across quartiles
      of CRP were 0.76, 0.74, 0.75, and 0.76 mm (p >0.5). In men there was a weak
      inverse association between CRP and ankle/brachial blood pressure index,
      independent of other risk factors, but no such association in women. Our findings
      indicate that CRP is not strongly and independently associated with prevalent
      atherosclerosis. Because CRP has been associated with clinical events, it could
      be that elevated CRP may be a stronger marker of thrombotic risk than of the
      degree of atherosclerosis.

PMID- 11448406
TI  - Usefulness of T-axis deviation as an independent risk indicator for incident
      cardiac events in older men and women free from coronary heart disease (the
      Cardiovascular Health Study).
AB  - T-axis shift has been reported to be an indicator of increased mortality risk. We
      evaluated the association of spatial T-axis deviation with incident coronary
      heart disease (CHD) events in older men and women free from clinically overt CHD.
      Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram
      of a subgroup of 4,173 subjects considered free of CHD at baseline in the
      Cardiovascular Health Study, a prospective cohort study of risk factors for CHD
      and stroke in older men and women. Cox regression analysis was used to evaluate
      the association of altered repolarization with the risk of incident CHD events.
      The prevalence of marked T-axis deviation (> or =45 degrees ) was 12%. During the
      median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all
      causes, and 679 incident CHD events. Adjusting for demographic and clinical risk
      factors, including other electrocardiographic abnormalities, there was a nearly
      twofold excess risk of CHD death, and approximately a 50% excess risk of incident
      CHD and all-cause mortality for those with marked T-axis deviation. From other
      electrocardiographic abnormalities, only QT prolongation was associated with
      excess risk for incident CHD comparable to that for abnormal T-axis deviation.
      These results suggest that T-axis deviation is an easily quantified marker for
      subclinical disease and an independent indicator for the risk of incident CHD
      events in older men and women free of CHD.

PMID- 11448407
TI  - Predictors and prognosis of suboptimal coronary blood flow after primary coronary
      angioplasty in patients with acute myocardial infarction.
AB  - We hypothesized that certain clinical and angiographic characteristics on
      presentation predict suboptimal infarct artery flow after percutaneous
      intervention during acute myocardial infarction (AMI). The goal of angioplasty
      (percutaneous transluminal coronary angioplasty [PTCA]) during AMI is the prompt
      restoration of normal flow to achieve myocardial reperfusion. However, inadequate
      epicardial coronary flow is observed in 10% to 20% of patients. From 2 large
      randomized trials-Global Use of Strategies To open Occluded arteries in Acute
      Coronary Syndromes-IIb, and Randomized Placebo-Controlled Trial of Platelet
      glycoprotein IIb/IIIa Blockade With Primary Angioplasty for Acute Myocardial
      Infarction-patients undergoing primary PTCA during AMI were included in the
      analysis. A multivariate logistic model was used to identify factors associated
      with final Thrombolysis In Myocardial Infarction (TIMI) flow grade < or =2. The
      891 patients were aged (mean +/- SD) 61 +/- 12 years, 75% were men, and 39% had
      an anterior wall AMI. Patients underwent PTCA within 4.8 +/- 3.2 hours from the
      onset of chest pain. The incidence of final TIMI 3 flow was 81%. TIMI flow grade
      < or =2 was independently associated with increasing age (odds ratio [OR] 1.39
      for every 10 years, 95% confidence interval [CI] 1.19 to 1.62), increasing heart
      rate (OR 1.16 for every 10 beats, 95% CI 1.05 to 1.28), and presence of visible
      thrombus on baseline angiogram (OR 1.89, 95% CI 1.18 to 3.05). Conversely,
      baseline TIMI 2 or 3 flow grade (OR 0.46, 95% CI 0.28 to 0.75) and left
      circumflex intervention (OR 0.42, 95% CI 0.23 to 0.79) correlated with normal
      postprocedural coronary flow. Mortality was significantly higher in patients with
      TIMI < or =2 than TIMI 3 flow grade (10.2% vs 1.5%, p <0.001, respectively).
      Thus, angiographic evidence of thrombus and 2 pivotal clinical characteristics,
      advanced age and elevated heart rate, predict lack of adequate coronary
      reperfusion. Conversely, the presence of normal or near-normal coronary flow
      before intervention correlates with a good angiographic result. Mortality risk is
      increased in patients with postprocedural suboptimal angiographic coronary flow.

PMID- 11448408
TI  - Prognostic value of cardiac troponin I re-elevation following percutaneous
      coronary intervention in high-risk patients with acute coronary syndromes.
AB  - Troponin I is a predictive marker of short- and intermediate-term adverse cardiac
      events in patients with acute coronary syndromes (ACS). These high-risk patients
      may benefit from early percutaneous coronary intervention. However, whether
      additional myocardial injury, defined as postprocedural troponin I elevation, may
      be associated with adverse short- and intermediate-term outcomes has not been
      fully explored. Accordingly, we studied 132 consecutive patients with non-ST
      elevation ACS (62% with non-Q-wave myocardial infarction) and elevated troponin I
      levels at admission (>0.15 ng/ml) who underwent percutaneous coronary
      intervention > or =48 hours after admission. Troponin I levels were routinely
      measured at 6 and 18 to 24 hours after intervention and patients were stratified
      according to the presence or absence of troponin I re-elevation, defined as
      postprocedural troponin I levels >1 times the admission levels. In-hospital and
      cumulative 6-month clinical outcomes were compared between groups. Patients with
      troponin I re-elevation (n = 51) were older (68 +/- 13 vs 64 +/- 12 years, p =
      0.05) and had experienced prior myocardial infarction more frequently (92.5 vs
      82.1, p = 0.09), but otherwise had similar baseline clinical characteristics.
      Patients with troponin I re-elevation had significantly higher in-hospital
      mortality (9.8% vs 0%, p = 0.016) and a higher 6-month cumulative death rate (24%
      vs 3.7%, p = 0.001). There was a trend for an increased 6-month myocardial
      infarction rate in patients with troponin I re-elevation (13.7% vs 3.7%, p =
      0.11) and target vessel revascularization was similar between groups (16.7% vs
      17.4%, p = 0.92). By multivariate analysis, troponin I re-elevation (odds ratio
      [OR] 6.2, p = 0.011) and diabetes mellitus (OR 5.7, p = 0.014) were the strongest
      independent predictors for increased 6-month cumulative mortality, whereas
      creatine kinase MB-fraction re-elevation had no prognostic value. We conclude
      that troponin I re-elevation after percutaneous coronary intervention in high
      risk patients with ACS is associated with a substantial increase in mortality and
      reduced event-free survival at 6-month follow-up.

PMID- 11448409
TI  - Incidence and mechanism of presyncope and/or syncope associated with paroxysmal
      junctional tachycardia.
AB  - The objectives of this study were to: (1) define the incidence of presyncope
      and/or syncope in patients with paroxysmal junctional tachycardias, (2) determine
      their causes, and (3) determine the outcome of symptoms. Syncope is a frequent
      problem and is often caused by paroxysmal tachycardia. The mechanism of
      hemodynamic instability is unknown. The population study consisted of 281
      patients, consecutively recruited because they had paroxysmal tachycardia and a
      sinus rhythm on a normal electrocardiogram. Fifty-two patients (group I) had
      presyncope and/or syncope associated with tachycardia. The remaining patients
      (group II) had no loss of consciousness. Transesophageal programmed atrial
      stimulation used 1 and 2 atrial extrastimuli, delivered in a control state, and
      if necessary, after infusion of 20 to 30 microg of isoproterenol. Arterial blood
      pressure was monitored. Vagal maneuvers and echocardiogram were performed in all
      patients. Paroxysmal tachycardia was induced in 51 group I patients and 227 group
      II patients. Comparisons of groups I and II revealed that age (50 +/- 21 vs 49 +/
      17 years), presence of heart disease (10% vs 10%), mechanism of tachycardia with
      a predominance of atrioventricular nodal reentrant tachycardia (70.5% vs 76%),
      and rate of tachycardia (196 +/- 42 vs 189 +/- 37 beats/min) did not differ
      between the groups. However, there were differences in both groups with regard to
      significantly higher incidences of positive vasovagal maneuvers (35% vs 4%, p
      <0.01), isoproterenol infusion required to induce tachycardia (55% vs 17%, p
      <0.001), and vasovagal reaction at the end of tachycardia (41% vs 4%, p <0.05).
      Thirty-seven group I patients underwent radiofrequency ablation of the reentrant
      circuit, which suppressed presyncope and/or syncope in 36 of the 37 patients.
      Thus, presyncope and/or syncope frequently complicated the history of patients
      with paroxysmal junctional tachycardia (18.5%). Several mechanisms are
      implicated, but vasovagal reaction was the most frequent cause. Treatment of the
      tachycardia typically suppressed presyncope and/or syncope.

PMID- 11448410
TI  - Important pressure recovery in patients with aortic stenosis and high Doppler
      gradients.
AB  - Pressure recovery has been described in aortic stenosis and may explain the
      difference occasionally observed between Doppler- and catheter-measured
      gradients. A narrow ascending aorta (AA) and moderately severe stenosis favors
      pressure recovery. The aims of this study were to investigate the degree to which
      these conditions are present in patients with aortic stenosis and high Doppler
      gradients and to evaluate the magnitude of pressure recovery. One hundred sixteen
      patients were examined with Doppler echocardiography before aortic valve
      replacement. Patients with a maximum gradient >70 mm Hg (n = 81) were included.
      The diameter of the AA was measured and compared with the diameter in an age- and
      body size-matched group of normal controls (n = 23). Pressure recovery was
      estimated from a previously validated equation by measuring the maximum Doppler
      gradient, the effective orifice area (EOA), and the diameter of the AA. The
      diameter of the AA was similar for patients (mean 3.0 cm, range 2.1 to 4.1) and
      normal controls (mean 3.0 cm, range 2.3 to 3.5). The maximum Doppler gradient was
      107 mm Hg (range 71 to 170) and the EOA was 0.6 cm(2) (range 0.2 to 1.3). The
      calculated pressure recovery was 18 mm Hg (range 6 to 37), which gives a net
      gradient of 89 mm Hg (range 51 to 151). Twenty-three percent had a net gradient
      <70 mm Hg. A cutoff of EOA/AA diameter at >0.2 cm identified 84% of patients (16
      of 19) with a net gradient <70 mm Hg. In conclusion, we found that important
      pressure recovery can be expected in most patients with aortic stenosis and high
      Doppler gradients. Pressure recovery may explain why some patients with high
      Doppler gradients are asymptomatic. Also, pressure recovery is a factor to
      consider in patients with atypical symptomatology and high Doppler gradients when
      one must decide on valvular replacement.

PMID- 11448411
TI  - Resynchronization pacing is a useful adjunct to the management of acute heart
      failure after surgery for congenital heart defects.
AB  - The acute hemodynamic effect of atrioventricular (AV) and inter/intraventricular
      (IV) resynchronization accomplished by temporary pacing using multiple epicardial
      pacing wires was evaluated in 20 children (aged 3.4 months to 14.0 years) after
      surgery for congenital heart defects fulfilling the following criteria: (1)
      presence of AV and/or IV conduction delay, and (2) need for inotropic support. AV
      resynchronization (n = 13) was achieved by AV delay optimization during atrial
      synchronous right ventricular outflow tract pacing. IV resynchronization (n = 14)
      was accomplished by atrial synchronous pacing from the right ventricular lateral
      wall in 7 patients with right bundle branch block and normal AV conduction and by
      atrial synchronous multisite ventricular pacing in another 7 patients with
      previously performed AV resynchronization. Compared with baseline values, AV
      resynchronization resulted in an increase in arterial systolic, mean, and pulse
      pressures by 7.2 +/- 8.3% (p <0.01), 8.6 +/- 8.1% (p <0.005), and 6.9 +/- 13.5%
      (p = NS), respectively. IV resynchronization used either alone or added to
      previously performed AV resynchronization led to a pressure increase of 7.0 +/-
      4.7%, 5.9 +/- 4.7%, and 9.4 +/- 7.8%, respectively (p <0.001 for all). The
      combined effect of AV and IV resynchronization resulted in a systolic, mean, and
      pulse pressure increase of 10.2 +/- 5.0% (range 4.0 to 19.1), 8.6 +/- 5.4% (range
      0.8 to 14.8), and 15.2 +/- 8.5% (range 6.1 to 33.3), respectively (p <0.001 for
      all). The increase in systolic arterial pressure after IV resynchronization was
      positively correlated with the initial QRS duration (r = 0.62, p <0.05) and
      extent of QRS shortening (r = 0.66, p <0.05). In conclusion, resynchronization
      pacing led to a significant increase in arterial blood pressure and was a useful
      adjunct to the treatment of acute postoperative heart failure in patients with AV
      and/or IV conduction delay.

PMID- 11448412
TI  - Acute hypertriglyceridemia is associated with peripheral vasodilation and
      increased basal flow in healthy young adults.
AB  - Prior studies suggest that acute elevations in plasma triglycerides alter
      vascular tone and impair endothelial function. To investigate the relation
      between acute hypertriglyceridemia and vascular function, we examined the effects
      of high- and low-fat meals on brachial artery reactivity in 14 healthy
      volunteers. Flow-mediated dilation declined from 14.7 +/- 8.3% to 10.6 +/- 6.2%
      after the high-fat meal only (p <0.001), and this decline was associated with a
      6% increase in baseline brachial artery diameter (3.50 +/- 0.74 mm to 3.70 +/-
      0.81 mm, p <0.001), but not a decrease in the arterial diameter during hyperemia.
      The high-fat meal increased serum triglycerides and insulin by 94% and 438%,
      respectively. To investigate the effects of triglyceride elevation in isolation
      from hyperinsulinemia, we examined vascular responses to an intravenous infusion
      of a triglyceride emulsion in 28 subjects. Triglyceride emulsion increased serum
      triglycerides 197% but had no effect on serum insulin. Brachial artery diameter
      increased 4%, from 3.68 +/- 0.51 mm to 3.81 +/- 0.56 mm (p <0.05), and forearm
      flow increased 36%, reflecting vasodilation of forearm resistance vessels. Flow
      mediated dilation and nitroglycerin-mediated dilation were unaffected. The
      triglyceride emulsion had no direct dilator effect on rabbit aortic tissue in
      vitro. In conclusion, acute hypertriglyceridemia is associated with vasodilation
      of conduit and resistance vessels in the arm and does not impair endothelial
      vasodilator function per se. The dilator effect is not insulin-dependent and does
      not appear to be a direct effect of triglycerides on vascular tissue.

PMID- 11448413
TI  - Relation between paroxysmal atrial fibrillation and left ventricular diastolic
      function in patients with acute myocardial infarction.
AB  - The relation between left ventricular filling pattern and the occurrence of
      paroxysmal atrial fibrillation was evaluated using Doppler echocardiography in a
      prospective series of 157 patients with acute myocardial infarction. Paroxysmal
      atrial fibrillation after acute myocardial infarction was often associated with a
      higher restrictive filling pattern.

PMID- 11448414
TI  - Effectiveness of the electronic medical record in cholesterol management in
      patients with coronary artery disease (Virtual Lipid Clinic).
AB  - This study demonstrates that the Virtual Lipid Clinic, an electronic medical
      record with computer-assisted cholesterol management, is associated with improved
      lipid management in patients with coronary artery disease. In comparison to
      traditional documentation methods with "pen and paper" charts, outpatient visits
      utilizing the electronic medical record were associated with a twofold increase
      in low-density lipoprotein (LDL) documentation, a threefold increase in achieving
      LDL goal, and a 30% increase in the use of lipid-lowering drugs.

PMID- 11448415
TI  - Measurement of plasma lipids in patients admitted with acute myocardial
      infarction or unstable angina pectoris.
AB  - We assessed the reliability of early (first day) plasma lipid measurements in
      patients admitted with acute myocardial infarction or unstable angina pectoris.
      In 55 such patients, plasma levels of cholesterol and triglycerides measured
      within the first 24 hours after admission were significantly lower than the
      corresponding values at 6 weeks, which means that even very early in-hospital
      lipid measurements could lead to potentially serious underestimation of the lipid
      risk in these patients ad defined by the current criteria.

PMID- 11448416
TI  - Time-dependent morphologic characteristics in angiographic chronic total coronary
      occlusions.
AB  - Intravascular ultrasound analysis of 70 chronic total occlusions (CTOs),
      conducted either before intervention or following dilation of a 1.5-mm balloon,
      showed that older CTOs have more complex plaque composition including a larger
      calcific burden. This may explain the adverse revascularization profile of older
      CTOs.

PMID- 11448417
TI  - Initial experience with multivessel percutaneous coronary intervention during
      mechanical reperfusion for acute myocardial infarction.
AB  - The feasibility and safety of simultaneous multivessel percutaneous coronary
      intervention during mechanical reperfusion for acute myocardial infarction was
      analyzed in a retrospective, case-controlled study. Patients who underwent
      multivessel coronary intervention had a higher risk of adverse clinical outcomes
      through 6 months compared with matched controls in whom coronary intervention was
      limited to the infarct-related artery.

PMID- 11448418
TI  - Effect of pravastatin in mildly hypercholesterolemic young men on serum matrix
      metalloproteinases.
AB  - Pravastatin decreases serum MMP-9 concentration in clinically healthy men. This
      may reflect reduction of nonsymptomatic chronic arterial inflammation.

PMID- 11448419
TI  - Correlation and stability of heart rate and ventricular ectopy variability in
      patients with congestive heart failure.
AB  - The stability of indexes of heart rate variability and their possible association
      with spontaneous variability of ventricular ectopy was examined in 13 patients
      with advanced congestive heart failure over 14 consecutive days of 24-hour
      ambulatory electrocardiographic recording. It was found that time and frequency
      domain measures of heart rate variability are stable over time and are inversely
      correlated with spontaneous variability of ventricular ectopy.

PMID- 11448420
TI  - Increased extraction of endothelin-1 across the failing human heart.
AB  - In this study we compared the transcardiac gradient of plasma endothelin-1 in
      patients with normal ventricular function and in those with congestive heart
      failure. We documented a significant reduction in the plasma levels of endothelin
      1 across the failing human heart, an effect not seen in patients with normal left
      ventricular function.

PMID- 11448421
TI  - Prognostic implications of increased QRS duration in patients with moderate and
      severe left ventricular systolic dysfunction.
AB  - Survival analysis was performed on a cohort of 2,265 patients with left
      ventricular ejection fraction of </= 40% to investigate the effect of increased
      QRS duration on all-cause mortality. Presence of QRS prolongation independently
      predicted higher mortality in patients with left ventricular systolic
      dysfunction. This finding may have important prognostic and therapeutic
      implications in this patient population.

PMID- 11448422
TI  - Comparison of effects of ioxaglate versus iomeprol on histamine and tryptase
      release in patients with ischemic cardiomyopathy.
AB  - We observed a release of histamine, but not of tryptase, in arterial blood from
      64 patients with ischemic heart disease and 24 patients without coronary disease,
      which was provoked by ioxaglate, a ionic compound, but was not provoked by
      iomeprol, a non-ionic radiocontrast compound. The release of histamine in
      arterial blood after ionic contrast medium injection was higher in patients with
      ischemic heart disease compared with patients without coronary disease,
      suggesting that an increased release from heart mast cells previously observed
      exists also for systemic blood basophils.

PMID- 11448423
TI  - Identification of uric acid and xanthine oxidase in atherosclerotic plaque.
AB  - Concentrations of uric acid in carotid endarterectomy specimens in men and women
      were measured using high-performance liquid chromatography in comparison wo
      nonatherosclerotic control specimens.

PMID- 11448424
TI  - Design of the therapeutic angiogenesis with recombinant fibroblast growth factor
      2 for intermittent claudication (TRAFFIC) trial.
AB  - The Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 for
      Intermittent Claudication (TRAFFIC) is a large, randomized, placebo-controlled,
      regimen-finding trial of intra-arterial recombinant fibroblast growth factor-2 in
      patients with intermittent claudication. This report describes the major design
      considerations and end points in TRAFFIC.

PMID- 11448425
TI  - Abnormal brachial artery flow-mediated vasodilation in young adults with major
      depression.
AB  - Depressive illness in patients without traditional risk factors for coronary
      artery disease is associated with striking abnormalities of endothelial function
      and elevation of circulating markers of atherosclerosis propensity. Further
      studies are needed to define the mechanisms that underlie these observations.

PMID- 11448427
TI  - Quality surgery begets patient safety.

PMID- 11448426
TI  - Spontaneous interpolated atrial premature complex detected by 12-lead ambulatory
      monitoring.
AB  - Spontaneous occurrence of an interpolated atrial premature complex, an unusual
      finding outside of the experimental electrophysiology laboratory, was detected
      and confirmed by evaluation of P-wave morphology in a patient who underwent 12
      lead ambulatory electrocardiography.

PMID- 11448428
TI  - The learning curve associated with pediatric laparoscopic splenectomy.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is technically difficult compared with
      open splenectomy. This report examines our experience with LS to define the
      learning curve. METHODS: The first 49 consecutive laparoscopic splenectomies were
      reviewed. Indications, complications, operative time, and costs were recorded.
      RESULTS: Indications included hereditary spherocytosis, immune thrombocytopenia
      purpura, beta-thalassemia, lymphoma, splenic cysts, and abscesses. Surgical time
      averaged 196 minutes for the first 10 patients, decreasing to 105 minutes for the
      last 10. Blood loss for the first 10 patients averaged 50 cc and less than 5 cc
      for the last 10. There were 3 complications and 1 conversion to open operation.
      Operative and hospital charges averaged $6,670 and $13,402, respectively, for the
      first 10 cases compared with $5,278 and $10,863 for the last 10. CONCLUSIONS: LS
      can be performed safely with few complications. LS has a steep learning curve in
      the first 20 patients after which operative times decrease along with overall
      costs.

PMID- 11448429
TI  - Initial experience with 150 cases of laparoscopic assisted colectomy.
AB  - BACKGROUND: Despite multiple reports of large series in the literature over the
      past decade, laparoscopic assisted colectomy (LAC) has not received widespread
      acceptance by the surgical community. Critics of LAC note concerns regarding
      unproved benefits and increased complexity of the procedures. The authors report
      their initial experience with 150 procedures. METHODS: A retrospective review of
      150 consecutive LACs was performed by the authors. RESULTS: Mean operative time
      for completed LAC, converted procedures, right, and sigmoid resections were 164
      minutes, 203 minutes, 121 minutes, and 177 minutes, respectively. Twenty-two
      patients had additional concurrent laparoscopic procedures. Thirty-nine patients
      had undergone previous abdominal surgery. The conversion rate was 12%. Mean
      length of stay for all patients was 4.5 days. There were 8 major and 16 minor
      complications. There were no port site metastases. Major complications and
      conversion rate decreased from the first 50 cases to the last 50 cases.
      CONCLUSIONS: LAC can be safely performed with superior quality of life outcomes
      in comparison with open colectomy. The authors believe that LAC will eventually
      become the gold standard for colon resection. The learning curve is discussed as
      an ongoing process, rather than a set number of procedures.

PMID- 11448430
TI  - Management and long-term follow-up of hepatic cysts.
AB  - PURPOSE: To provide an algorithm for the management of hepatic cysts through an
      analysis of our series over 16 years. METHOD: We reviewed the surgical management
      and outcome of patients with hepatic cysts between 1984 and 2000 at a single
      institution. Data were collected by chart review, telephone interview, and follow
      up hepatic ultrasonography. RESULTS: Forty-four patients (36 females, 8 males)
      underwent a total of 46 operations for hepatic cysts (mean size 12.0 +/- 5.2 cm)
      with a mean follow-up of 5.1 +/- 4.0 years. We treated 28 simple cysts, 4
      polycystic liver disease (PCLD), 7 cystadenomas, 2 hydatid cysts, 1
      cystadenocarcinoma, 1 endometrioma, and 1 hepatic foregut cyst. Operations
      included simple drainage, wide unroofing (open and laparoscopic), and hepatic
      resection. Four patients experienced a symptomatic recurrence after definitive
      treatment; 3 of these patients had PCLD. Four of the 7 patients with cystadenomas
      had undergone previous operations that required subsequent definitive resection
      without a recurrence. CONCLUSIONS: The preoperative distinction between simple
      cysts and cystadenomas/cystadenocarcinomas can be difficult, yet the management
      is different. Unroofing is a safe and effective operation for patients with
      simple cysts. Patients with PCLD frequently have recurrences. Cystadenomas should
      be completely resected owing to the likelihood of recurrence after partial
      excision and the risk of eventual cystadenocarcinoma. We present a treatment
      algorithm for the preoperative evaluation and management of hepatic cysts based
      on the largest number of patients with the longest follow-up reported to date.

PMID- 11448431
TI  - A pancreatic ductal leak should be sought to direct treatment in patients with
      acute pancreatitis.
AB  - BACKGROUND: The end result of leakage of pancreatic juice into the peripancreatic
      space can be sterile necrosis, infected necrosis, or rupture into an adjacent
      hollow viscus or blood vessel (eg, colon, small bowel, or pseudoaneurysm). If a
      pancreatic duct (PD) leak is present, should treatment be aimed at minimizing the
      sequela of the leakage of pancreatic juice and not just supportive observation
      until a necrosectomy is required? METHODS: In 144 patients with severe
      pancreatitis we investigated whether the presence of a PD leak was associated
      with necrosis and also asked if PD leak might predict other outcomes such as a
      length of stay (LOS), mortality, and need for surgery. Furthermore, we questioned
      whether the use of endoscopic retrograde cholangiopancreatography (ERCP) to
      search for a PD leak might worsen the clinical outcome because of the potential
      for introducing microorganisms into an undrained space or exacerbating
      pancreatitis. RESULTS: The presence of a demonstrable pancreatic duct leak was
      observed in 37% of patients and was significantly associated with both a higher
      incidence of necrosis and prolonged LOS (> or = 20 days). These patients were 3.4
      times more likely to have necrosis and 2.6 times more likely to have a prolonged
      LOS. When treated with a combination of percutaneous drains, pancreatic duct
      stents, and surgery as necessary, a PD leak (even with its higher necrosis rate)
      was not significantly correlated with either mortality or the need for
      necrosectomy. The use of ERCP was not associated with LOS, mortality, or the need
      for necrosectomy, provided discovered PD leaks were immediately drained.
      CONCLUSIONS: A PD leak is common in patients with pancreatic necrosis but it is
      also important to locate and decompress in order to impede progression of the
      disease and keep mortality low.

PMID- 11448432
TI  - Bedside peritoneal drainage in very low birth weight infants.
AB  - BACKGROUND: Bedside peritoneal drainage is emerging as a useful therapy for
      premature infants with intestinal perforation in the newborn period. Some authors
      recommend that bedside drainage be primary therapy for very low birth weight
      neonates. Surprisingly, some series report up to 70% of neonates so treated never
      require further or definitive surgery. METHODS: This is a retrospective chart
      review of all premature newborns with a diagnosis of either necrotizing
      enterocolitis or bowel perforation between November 1996 and May 2000. RESULTS:
      Sixty-seven patients were identified, of whom 27 were treated medically only and
      not considered here. Thirty-two neonates were treated with laparotomy primarily,
      with 26 survivors. Eight neonates were treated first with bedside peritoneal
      drainage. Of these, 4 survived, 6 required secondary surgery for obstruction or
      infection, and 2 died before any further intervention. CONCLUSIONS: Bedside
      peritoneal drainage is a useful adjunct in the approach to treating the very
      sick, very low birth weight neonate with evidence of intestinal perforation. Our
      experience does not support drainage as definitive therapy.

PMID- 11448433
TI  - Does telomerase activity add to the value of fine needle aspirations in
      evaluating thyroid nodules?
AB  - BACKGROUND: Telomerase replaces DNA sequences that are lost with cell division.
      Increased activity has been documented in malignant cells. Fine needle aspiration
      (FNA) has a 90% sensitivity for diagnosis of papillary carcinomas, but a
      specificity of 52%. This often leads to unnecessary surgery. METHODS: Telomeric
      repeat amplification protocol assays were performed on FNA specimens of thyroid
      nodules in 19 patients. These results were compared with the surgical pathology
      using chi-square analysis. RESULTS: There were 5 malignant and 14 benign nodules.
      Telomerase activity was found in 3 of 5 malignant (60%) and 9 of 14 benign (64%):
      sensitivity was 60%, specificity was 36%. CONCLUSION: Telomerase assays did not
      add any additional information to FNA alone. Inflammatory changes associated with
      benign and malignant lesions can possess telomerase activity independent of the
      malignant state.

PMID- 11448434
TI  - Usefulness of preoperative lymphoscintigraphy for the identification of sentinel
      lymph nodes in melanoma.
AB  - BACKGROUND: The exact role of lymphoscintigraphy (LS) in the evaluation of
      sentinel lymph nodes (SLNs) in melanoma is controversial. METHODS: We reviewed
      our experience with preoperative LS for the determination of the lymph node
      drainage pattern of clinically node negative primary melanomas, with attention to
      the rate of ambiguous drainage and the effect of previous wide local excision
      (WLE). RESULTS: The scans of 87 patients who underwent LS at our institution for
      evaluation of their primary melanomas from 1995 to the present were reviewed.
      Fourteen of the primary tumor sites were in the head and neck region, 41 were
      truncal, and 32 were in the extremities. The average tumor thickness was 2.6 mm.
      Nine of 14 (64%) head/neck lesions and 12 of 41 (29%) truncal lesions displayed
      ambiguous drainage, as compared with only 2 of 32 (6%) extremity lesions (P
      <0.05). Forty-one of the 87 patients (47%) had undergone previous WLE of their
      primary lesion prior to their LS. The number of draining basins for the WLE and
      the non-WLE groups were not significantly different, and at least one SLN was
      found for all WLE cases. CONCLUSIONS: Preoperative LS is important for the
      treatment planning of SLN biopsy for head/neck and truncal melanomas, but adds
      little additional information for extremity lesions. Lymph node drainage scans
      and subsequent SLN biopsies are not contraindicated in the presence of a prior
      WLE.

PMID- 11448435
TI  - Evaluation of feasibility and accuracy of sentinel node biopsy in early breast
      cancer.
AB  - BACKGROUND: Current literature has suggested that sentinel node biopsy may
      eventually replace axillary dissection as the nodal staging procedure of choice
      in early breast cancer. The goals of our study were to determine the accuracy of
      the sentinel node in predicting axillary nodal status and to evaluate the
      feasibility of incorporating sentinel node biopsy into a general surgical
      practice. METHODS: Between June 1999 and August 2000, 158 clinically node
      negative women with a histological diagnosis of T1 or T2 breast cancer were
      enrolled in the study. Both technetium sulfur colloid radiotracer and isosulfan
      blue dye were used to guide sentinel node biopsy. Sentinel node biopsy was always
      followed by a complete axillary dissection. The histopathology of sentinel nodes
      using serial sectioning and cytokeratin immunohistochemistry was compared with
      that of the nonsentinel nodes evaluated with routine hematoxylin and eosin stain.
      RESULTS: The overall sentinel node detection rate was 84% (89 of 106 patients).
      Sentinel node biopsy was most successful when a combination of radiotracer and
      dye was used. The staging accuracy of sentinel node biopsy was 98% (87 of 89);
      the sensitivity of the method was 94% (34 of 36); the false negative rate was 6%
      (2 of 36); the negative predictive value was 96% (53 of 55); and the rate of
      metastases to the sentinel node only was 56% (20 of 36). The results varied
      considerably among surgeons. CONCLUSIONS: The findings in our study support the
      hypothesis that the sentinel node is an accurate predictor of axillary nodal
      status in women with early breast cancer. These results suggest that the
      excellent findings in the literature can be reproduced by a group of general
      surgeons in a community-based hospital.

PMID- 11448436
TI  - Genetic counseling impacts decision for prophylactic surgery for patients
      perceived to be at high risk for breast cancer.
AB  - BACKGROUND: This study addresses the impact a comprehensive genetic counseling
      program had on women considering prophylactic mastectomy or oophorectomy.
      METHODS: Sixty patients underwent detailed family evaluation and risk was
      estimated. Recommendations were made regarding testing. Ramifications of testing
      were discussed in detail. RESULTS: Thirty-one women (37%) were considering
      prophylactic surgery believing themselves to be at high risk. Of these, 23 had
      testing recommended. Seven patients proceeded with prophylactic surgery based
      solely on high-risk assessment. Ten women were tested; five were positive. Three
      patients proceeded with prophylactic surgery despite a negative test. One decided
      against surgery despite a positive test. After counseling, prophylactic surgery
      was performed in just over half the initial candidates. CONCLUSIONS: Breast
      cancer risk estimation and genetic evaluation can be complex. Comprehensive
      genetic risk assessment programs can play a significant role in the management of
      patients considering prophylactic surgery for perceived high risk.

PMID- 11448437
TI  - Axillary web syndrome after axillary dissection.
AB  - BACKGROUND: Some patients undergoing axillary lymph node dissection (ALND)
      experience postoperative pain and limited range of motion associated with a
      palpable web of tissue extending from the axilla into the ipsilateral arm. The
      purpose of this study is to characterize the previously undescribed axillary web
      syndrome (AWS). METHODS: To identify patients with AWS, a retrospective review
      was performed of all invasive breast cancer patients treated by a single surgeon
      (REM) between 1980 and 1996. Records were also reviewed of 4 more recent patients
      who developed AWS after undergoing sentinel node lymph node dissection (SLND)
      without ALND. RESULTS: Among 750 sequentially treated patients, 44 (6%) developed
      AWS between 1 and 8 weeks after their axillary procedure. The palpable
      subcutaneous cords extended from the axillary crease down the ipsilateral arm,
      across the antecubital space, and in severe cases down to the base of the thumb.
      The web was associated with pain and limited shoulder abduction (< or = 90
      degrees in 74% of patients). AWS resolved in all cases within 2 to 3 months. AWS
      also occurred after SLND. Tissue sampling of webs in 4 patients showed occlusion
      in lymphatic and venous channels. CONCLUSIONS: AWS is a self-limiting cause of
      morbidity in the early postoperative period. More limited axillary surgery, with
      less lymphovenous disruption, might reduce the severity and incidence of this
      syndrome, although SLND does not eliminate its occurrence.

PMID- 11448438
TI  - Does neoadjuvant chemoradiation downstage esophageal carcinoma?
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy is administered to patients with
      esophageal carcinoma with the belief that this will both downstage the tumor and
      improve survival. Endoscopic ultrasound (EUS) is currently the most accurate
      method of staging esophageal cancer for tumor (T) and lymph node (N) status.
      Because both EUS and neoadjuvant therapy for esophageal carcinoma are relatively
      new, there are few data examining the relationship between EUS stage and
      histological stage (the stage after resection) in patients receiving neoadjuvant
      therapy. METHODS: To determine the effect of neoadjuvant chemoradiotherapy on T
      and N stage as determined by EUS, we retrospectively compared two groups of
      patients with esophageal cancer staged by EUS. One group (33 patients) underwent
      neoadjuvant therapy (Walsh protocol: 5-fluorouracil, cisplatin, and 4000 rads of
      external beam radiation) followed by resection. The second group (22 patients), a
      control group, underwent resection without neoadjuvant therapy. We then compared
      histological stage to determine if there was a downstaging in the patients
      receiving neoadjuvant therapy. Survival was evaluated as well. RESULTS: EUS
      accurately predicted histologic stage. In the control group EUS overestimated T
      stage in 3 of 22 (13%), underestimated N stage in 2 of 22 (9%), and overestimated
      N stage in 2 of 22 (9%) of patients. Preoperative radiochemotherapy downstaged
      (preoperative EUS stage versus pathologic specimen) 12 of 33 (36%) of patients
      whereas only 1 of 22 (5%) of patients in the control group was downstaged.
      Complete response (no tumor found in the surgical specimen) was observed in 5 of
      33 (15%) of patients receiving radiochemotherapy. Survival was prolonged
      significantly in patients receiving radiochemotherapy: 20.6 months versus 9.6
      months for those (stage II or III) patients not receiving radiochemotherapy (P
      <0.01). Operative time, operative blood loss, and length of stay were not
      significantly different between groups. Perioperative mortality was higher in the
      radiochemotherapy group (13%) compared with the no radiochemotherapy group (5%)
      but did not achieve statistical significance. CONCLUSIONS: EUS accurately stages
      esophageal carcinoma. Neoadjuvant radiochemotherapy downstages esophageal
      carcinoma for T and N status. In our nonrandomized study, neoadjuvant therapy
      conferred a significant survival advantage. Operative risk appears to be
      increased in patients receiving neoadjuvant radiochemotherapy prior to
      esophagectomy.

PMID- 11448439
TI  - A changing experience with primary hyperparathyroidism at Group Health
      Cooperative, Seattle.
AB  - BACKGROUND: Since 1996 new technologies have been brought to bear on the
      treatment of primary hyperparathyroidism. The Tc 99m sestamibi scan is useful in
      defining the location of a solitary adenoma, and used in combined with the gamma
      probe, it facilitates the removal of a solitary adenoma with a degree of accuracy
      and a cure rate previously not available. Intraoperative measurement of
      parathyroid hormone is also being used to judge immediately if the surgery has
      been successful. METHODS: This is a retrospective review of all cases of primary
      hyperparathyroidism treated surgically at Group Health Cooperative, Seattle,
      Washington, from April 1997 until June 2000. RESULTS: Of the 49 procedures in 47
      patients, 44 had a sestamibi scan preoperatively. Fifteen patients had a
      combination of the sestamibi scan done on the day of surgery and the
      intraoperative use of the gamma probe. This has been labeled minimally invasive
      radioguided parathyroidectomy (MIRP). The procedures are divided into two groups.
      The 28 procedures before the advent of MIRP are labeled group A. The 22
      procedures after the advent of MIRP are labeled group B. One patient with two
      procedures is represented in both groups. They are further differentiated into
      three groups in terms of surgical difficulty: routine, difficult, and complex.
      Eleven procedures are in the difficult category and 3 procedures are classified
      in the complex category. Since the start of MIRP on May 14, 1999, there have been
      15 MIRPs and 7 procedures requiring a standard incision. Group A is compared with
      group B using a variety of parameters. CONCLUSIONS: The combination of the Tc 99m
      sestamibi scan on the day of surgery and the use of the gamma probe
      intraoperatively is a major advance in the treatment of primary
      hyperparathyroidism. A significant number of difficult and complex cases must
      still be treated with bilateral neck exploration, including patients with
      hyperplasia, double adenoma, carcinoma and patients with underlying thyroid
      pathology. There is a "surgery time" advantage to the surgeon who does more than
      10 cases per year.

PMID- 11448441
TI  - Comparison of carotid endarterectomy at high- and low-volume hospitals.
AB  - BACKGROUND: Population-based studies have demonstrated better outcomes for
      carotid endarterectomies at high-volume hospitals. METHODS: This is a 2-year
      retrospective review of carotid procedures at two low-volume hospitals (n = 156)
      and one high-volume hospital (n = 404) in the metropolitan area of Portland,
      Oregon. RESULTS: There were no significant differences in 30-day mortality and
      stroke rates for carotid endarterectomies when comparing low- and high-volume
      hospitals (P = 0.59). These were comparable rates despite the fact that the low
      volume hospitals had significantly older patients (P <0.001), more smokers (P
      <0.001), more patients with an indication of a previous nondisabling stroke (P
      <0.01), and fewer patients who were asymptomatic (P <0.01). CONCLUSION: The
      regionalization of carotid endarterectomy into high-volume hospitals is not
      justified by the findings of this study. Carotid endarterectomy performed by well
      trained, experienced surgeons in low-volume hospitals is a safe procedure.

PMID- 11448442
TI  - A prospective evaluation of dietary status and symptoms after near-total
      esophagectomy without gastric emptying procedure.
AB  - BACKGROUND: After esophagectomy, the stomach is the most commonly utilized
      reconstructive conduit. There remains debate among surgeons regarding the
      requirements for pyloroplasty/pyloromyotomy following reconstruction. We present
      a series of patients having undergone near total esophagectomy and reconstruction
      with gastric tube without gastric emptying procedure to analyze critically these
      patients' ability to reestablish a subjectively acceptable and nutritionally
      adequate eating pattern without significant side effects of early satiety,
      dumping, or diarrhea. METHODS: Between 1991 and 1998, 48 patients underwent
      esophagectomy utilizing this technique and were available for long-term follow-up
      and nutritional assessment. Patient weights were recorded at 2 weeks, 6 months,
      and 1 year and a telephone interview conducted at a mean of 36 months
      postoperatively for the evaluation of eating patterns and symptoms. A subgroup of
      these patients (32 of 48) completed a 3-day dietary record that was assessed by a
      certified nutritionist. This patient group included 10 patients (21%) who had
      received perioperative chemoradiotherapy. RESULTS: Dietary intake was
      characterized as normal or minimally limited in 41 patients (85%). Those who had
      received perioperative chemoradiotherapy needed no significant increased time to
      return to a normal dietary baseline (6.1 versus 5.9 months). Mean weight loss
      prior to surgery was 3 kg. Weight loss continued for the first 6 months (mean 10
      kg); however, 63% were able to gain weight from 6 months to 1 year following
      surgery (mean 3 kg). Most patients were overweight prior to operation (mean 115%
      of ideal body weight) and achieved a new postoperative baseline (mean 104% of
      ideal body weight) at 1 year. Patients demonstrated a mean daily caloric intake
      of 2,179 kilocalories per day, which was 98% of recommended according to their
      ideal body weight. Postoperative symptoms of short-term nausea (19%), occasional
      dysphagia with certain foods (38%), mild increased stool frequency (15%), and
      occasional regurgitation (25%) were noted. CONCLUSIONS: Near-total esophagectomy
      with verticalized gastric tube without a gastric emptying procedure is well
      tolerated and allows a return to subjectively acceptable and nutritionally
      appropriate dietary eating pattern without significant associated side effects.

PMID- 11448443
TI  - Use of the radial forearm free tissue flap to treat persistent stricture after
      esophagogastrectomy.
AB  - BACKGROUND: Persistent stricturing or anastomotic leakage at the cervical
      esophagogastric anastomosis can be a troublesome complication of gastric pull-up
      procedures. When the stricture is the result of ischemia of the stomach, the
      strictures are long and often not responsive to dilatation and require large
      operations such as jejunal interposition or replacement with colonic pull-up. In
      this report we describe the use of a radial forearm flap to patch strictures.
      METHODS: The radial forearm flap is a fascia cutaneous flap taken from the
      forearm and based on the radial artery and its venae comitantes. The advantages
      of this flap are that it is thin and pliable, conforms easily, has excellent
      reliability due to the size of the feeding vessels, and has a relatively long
      pedicle. The vascular anastomosis can be made to several arteries and veins
      within the neck. The epithelial component can be made in sizes up to 10 by 20 cm.
      RESULTS: We have used the radial forearm flap to patch strictures in 6 patients
      with persistent complex strictures in the cervical region after esophagectomy.
      Results were excellent in 4 patients (able to eat liquids and solids without
      problems) and good in 1 patient (liquids okay, some problem with solids), and 1
      patient died postoperatively. Follow-up is 4 months to 7 years. CONCLUSIONS: The
      radial forearm flap is an excellent option for handling persistent stricture
      after esophagogastrectomy. In many instances, this flap can be used in lieu of a
      jejunal interposition flap and obviates a laparotomy to harvest jejunum. The flap
      fits easily into the neck and conforms to the space.

PMID- 11448444
TI  - Intentional injury treated in community hospitals.
AB  - BACKGROUND: The impact of intentional injury in major metropolitan trauma centers
      has been established. Nonaccidental injury has become an increasingly important
      component of trauma care in mid-sized urban areas. To determine the medical and
      economic impact of personal violence in the Spokane, Washington, community we
      undertook a 5-year retrospective review. PATIENTS AND METHODS: Trauma registries
      were used to identify all victims of intentional injury admitted between May 1,
      1994, and April 31, 1999. Demographic data, blood alcohol, mechanism, injury
      severity, hospital course, and outcome were abstracted from the registries.
      Financial data were obtained from hospital financial offices. SETTING: Spokane,
      Washington, has a population of 200,000 with 400,000 in the metropolitan area.
      Trauma patients are triaged to hospitals according to Washington Administrative
      Code guidelines, supervised by central medical control. The two level II and two
      level III facilities are staffed by private practice surgeons and serve a
      referral area of 650,000. RESULTS: Five hundred eighty-one intentional injury
      patients were admitted. This represented 15% of all significant injuries. Males
      accounted for 80% of the patients and 84%were Caucasian. The mean patient age was
      30 years, only one quarter were listed as employed. Sixteen percent of the
      injuries were self-inflicted, gunshot was the most common mechanism (39%).
      Alcohol was involved in one half of the injuries. Sixty-three patients died, 39
      died prior to intensive care unit admission. Hospital stay averaged 6.4 days,
      with a mean hospital charge of $18,000. Hospitals were reimbursed at 67%.
      Surgeons collected 31% of billed fees. Fewer than one third of patients had any
      form of private insurance. CONCLUSIONS: Intentional injury is a significant
      component of trauma care in our community. Patients are seriously injured and the
      fatality rate is high. Care is expensive and poorly funded.

PMID- 11448445
TI  - Pharyngeal pH measurements in patients with respiratory symptoms before and
      during proton pump inhibitor therapy.
AB  - BACKGROUND: Pharyngeal pH monitoring is a diagnostic tool used to identify
      Gastroesophageal reflux disease (GERD) as an etiology of respiratory symptoms. We
      performed pharyngeal pH monitoring on 14 patients with respiratory symptoms
      thought to be induced by GERD. METHODS: Symptoms and pH monitoring (esophageal
      and pharyngeal) were assessed prior to and 3 months after the initiation of
      double-dose proton pump inhibitor therapy. RESULTS: Symptoms included cough,
      hoarseness, and throat clearing. Ten patients had at least one episode of
      pharyngeal reflux (PR+) and 4 patients had no pharyngeal reflux (PR-). Pharyngeal
      reflux episodes in PR+ patients decreased from 3.5 to 0.9 (P <0.05) per day with
      8 of 10 (80%) patients having elimination or reduction of such episodes. Eight of
      9 PR+ patients (89%) with suppressed pharyngeal reflux on medical therapy had
      resolution of respiratory symptoms. Three of 4 PR- patients (75%) had persistent
      symptoms on medical therapy. CONCLUSIONS: Proton pump inhibitor therapy improves
      clinical symptoms and decreases pharyngeal reflux episodes in patients with
      respiratory symptoms related to GERD. Direct measurement of pharyngeal pH is
      helpful in the identification of patients likely to respond to antireflux
      therapy.

PMID- 11448446
TI  - Quality of life before and after laparoscopic Heller myotomy for achalasia.
AB  - BACKGROUND: Because the surgical treatment of achalasia is directed at the
      palliation of chronic symptoms, it is important to assess how surgery affects
      patients' health-related quality of life (HRQL). METHODS: We evaluated upper
      gastrointestinal symptoms, satisfaction, and HRQL in 19 patients with achalasia
      before and after undergoing a laparoscopic Heller myotomy and partial
      fundoplication. HRQL was assessed using the Medical Outcomes Study 36-item short
      form health survey (SF-36). RESULTS: The mean age of the patients was 40 years
      (range 16 to 74), and 58% were men. After a median follow-up of 21 months (range
      2 to 35), 12 of 16 patients were satisfied with the results of their surgery.
      Liquid and solid dysphagia scores were improved after surgery, and the prevalence
      of heartburn symptoms did not change. Although all the health concepts measured
      by the SF-36 instrument showed some improvement, statistically significant
      increases (on a 0 to 100 scale) were detected in physical functioning (11.1, P =
      0.02), role-physical (25.0, P = 0.05), bodily pain (12.2, P = 0.01), vitality
      (13.7, P = 0.02), and social functioning (18.4, P = 0.02). CONCLUSIONS: Most
      aspects of HRQL improve after a laparoscopic Heller myotomy and partial
      fundoplication for achalasia.

PMID- 11448447
TI  - Late mortality after orthotopic liver transplantation.
AB  - BACKGROUND: Mortality within the first year after orthotopic liver
      transplantation (OLTx) is usually due to infection or allograft failure. Late
      complications leading to death after OLTx have not been extensively evaluated.
      The aim of this study was to determine the incidence of late mortality and to
      identify the most common causes and risk factors associated with late mortality
      after OLTx. METHODS: A total of 479 OLTx were performed in 459 patients (320
      males, 139 females; mean age 47 years, range 13 to 69) between September 1991 and
      April 2000. All patient deaths among liver transplant recipients who survived
      more than 1 year after transplantation (follow-up mean 3.4 years, median 3, range
      1 to 8.6) were reviewed. RESULTS: In all, 122 allografts (24%) were lost in 109
      patients during the study period (24%). Seventy-five allografts were lost in 69
      patients by 1 year (15%). Forty-seven allografts were lost in 40 patients who
      survived at least 1 year (9.6%). Actuarial survivals at 2 years, 5 years, and 9
      years were 95%, 85%, and 80%, respectively (based on 100% survival at 1 year).
      The causes of the late mortality were malignancy (9 patients), disease recurrence
      (8), late infection (6), renal failure complications (5), cardiovascular
      complications (4), chronic rejection (3), gastrointestinal hemorrhage (2),
      medication noncompliance (1), and unknown (2). CONCLUSIONS: Malignancy and
      disease recurrence are the major causes of late mortality among adult OLTx
      recipients. Pharmacologic immunosuppression is associated with many of the causes
      of late mortality. Advances in immunosuppression with less toxicity may improve
      long-term survival after OLTx.

PMID- 11448448
TI  - Neurotransmitters and apoptosis in the developing brain.
AB  - In the immature mammalian brain during a period of rapid growth (brain growth
      spurt/synaptogenesis period), neuronal apoptosis can be triggered by the
      transient blockade of glutamate N-methyl-d-aspartate (NMDA) receptors, or the
      excessive activation of gamma-aminobutyric acid (GABA(A)) receptors. Apoptogenic
      agents include anesthetics (ketamine, nitrous oxide, isoflurane, propofol,
      halothane), anticonvulsants (benzodiazepines, barbiturates), and drugs of abuse
      (phencyclidine, ketamine, ethanol). In humans, the brain growth spurt period
      starts in the sixth month of pregnancy and extends to the third year after birth.
      Ethanol, which has both NMDA antagonist and GABA(A) agonist properties, is
      particularly effective in triggering widespread apoptotic neurodegeneration
      during this vulnerable period. Thus, maternal ingestion of ethanol during the
      third trimester of pregnancy can readily explain the dysmorphogenic changes in
      the fetal brain and consequent neurobehavioral disturbances that characterize the
      human fetal alcohol syndrome. In addition, there is basis for concern that agents
      used in pediatric and obstetrical medicine for purposes of sedation, anesthesia,
      and seizure management may cause apoptotic neuronal death in the developing human
      brain.

PMID- 11448449
TI  - Oxidation of prostaglandin H(2) and prostaglandin H(2) analogues by human
      cytochromes P450: analysis of omega-side chain hydroxy metabolites and four
      steroisomers of 5-hydroxyprostaglandin I(1) by mass spectrometry.
AB  - The objective was to examine the NADPH-dependent oxygenation of prostaglandin
      H(2) (PGH(2)) and three PGH(2) analogues, 9,11-diazo-15-deoxy-PGH(2) (U51605),
      9,11-epoxymethano-PGH(2) (U44069), and 11,9-epoxymethano-PGH(2) (U46619), by
      cytochromes P450, and to characterize the metabolites by mass spectrometry.
      CYP2C19, CYP4A11, CYP4F8, and liver and renal cortical microsomes oxidized the
      omega-side chain of U44069, U46619, and U51605, whereas only CYP4F8 oxidized the
      omega-side chain of PGH(2). PGH(2) was transformed to four stereoisomers of 5
      hydroxy-PGI(1) by recombinant cytochromes P450. CYP4F8 formed the 5-hydroxy
      PGI(1) isomers in small amounts compared to the 19-hydroxy metabolites of PGH(2).
      Isomers of 5-hydroxy-PGI(1) and 6-keto-PGF(1 alpha) were detectable when PGH(2)
      decomposed in the presence of hemin, hemoglobin, or heat-inactivated microsomes.
      5-Hydroxy-PGI(1) is likely formed from PGH(2) in a pseudo-enzymatic reaction
      involving homolytic scission of the endoperoxide and formation of an ether
      between C-9 and C-6 and a carbon-centered radical at C-5, which reacts with
      molecular oxygen. CYP4F8 catalyzes 19-hydroxylation of PGH(2), but the absolute
      configuration of the 19-hydroxy group is unknown, whereas human seminal fluid
      contains (19R)-hydroxy-PGE(2). CYP4F8 was found to metabolize U51605 to 90% of
      the (19R)-hydroxy metabolite, providing further evidence in favor of a role of
      CYP4F8 in biosynthesis of (19R)-hydroxy PGE in human seminal vesicles. We
      conclude that omega-side chain hydroxylation of PGH(2) analogues may be catalyzed
      by many different cytochromes P450, but only CYP4F8 oxidizes the omega-side chain
      of PGH(2) efficiently.

PMID- 11448450
TI  - Verapamil-stimulated glutathione transport by the multidrug resistance-associated
      protein (MRP1) in leukaemia cells.
AB  - Multidrug resistance mediated by the multidrug resistance-associated protein MRP1
      is associated with decreased drug accumulation, which is in turn dependent on
      cellular glutathione. We have reported that verapamil, an inhibitor of drug
      transport, caused a decrease in cellular glutathione in CCRF-CEM/E1000 MRP1
      overexpressing leukaemia cells (Biochem Pharmacol 55;1283--9, 1998). We now
      demonstrate that other inhibitors of MRP1-mediated drug transport (e.g. MK571,
      indomethacin, genistein, and nifedipine) deplete cellular glutathione in these
      leukaemia cells (>30% decrease; P < 0.01) while having no effect on the parental
      CCRF-CEM cells. However, treatment with etoposide or vincristine (at similar
      molar concentrations) caused a 20% decrease in glutathione. Verapamil-stimulated
      glutathione transport correlated with MRP1 expression in a series of drug
      resistant cells, and glutathione was quantitatively recovered in the
      extracellular media. Further, verapamil-stimulated glutathione transport was
      rapid (50% decrease in 10 min), dose-dependent, and inhibited by vanadate, an
      inhibitor of ATPase activity, but not by sulphobromophthalein (BSP) or
      methionine, inhibitors of hepatic glutathione transporters. Incubation of CCRF
      CEM/E1000 cells in 25 mM glutathione not only showed that verapamil-mediated
      efflux occurred against the concentration gradient, but also demonstrated the
      MRP1-mediated uptake of glutathione (P < 0.01 compared to the parental CCRF-CEM
      cells), which was not inhibited by vanadate. These results demonstrate that while
      MRP1 transports glutathione in the presence of inhibitors of drug transport,
      there is no convincing evidence for co-transport of glutathione with drug. They
      further demonstrate that MRP1 mediates the facilitated transport of glutathione
      into the MRP1-overexpressing CEM/E1000 cells, suggesting that MRP1 may play a
      major role in cellular glutathione homeostasis.

PMID- 11448451
TI  - Inhibition by guanosine cyclic monophosphate (cGMP) analogues of uptake of
      [(3)H]3',5'-cGMP without stimulation of ATPase activity in human erythrocyte
      inside-out vesicles.
AB  - The cellular extrusion of guanosine 3',5'-cyclic monophosphate (3',5'-cGMP) is a
      unidirectional ATP-dependent process that is inhibited by probenecid, a non
      selective transport inhibitor of organic anions. In the present study, various
      cGMP analogues were tested for their ability to inhibit 3',5'-cGMP efflux and
      stimulate the cGMP-selective ATPase in human erythrocytes. The difference in
      uptake of 1 microM [(3)H]3',5'-cGMP to inside-out vesicles in the presence and
      absence of 1 mM ATP at 37 degrees was defined as active transport. Two ATP
      dependent components were detected for unlabelled 3',5'-cGMP (0.01--100 microM)
      with respective K(i) of 1.3 +/- 0.2 and 280 +/- 50 microM (mean +/- SEM, N = 3).
      The high-affinity transport was inhibited by the analogues with a typical
      pattern: Rp-monophosphorothioate guanosine 3',5'-cyclic monophosphate (Rp-cGMPS)
      > 3',5'-cGMP > 2'-O-monobutyryl guanosine 3',5'-cyclic monophosphate (O-mb-cGMP)
      approximately N(2)-monobutyryl guanosine 3',5'-cyclic monophosphate (N-mb-cGMP) >
      or = N(2),2'-O-dibutyryl guanosine 3',5'-cyclic monophosphate (Db-cGMP)
      approximately 8'-bromo guanosine 3',5'-cyclic monophosphate (Br-cGMP)
      approximately Guanosine 2',3'-cyclic monophosphate (2'3'-cGMP) > Sp
      monophosphorothioate guanosine 3',5'-cyclic monophosphate (Sp-cGMPS). A
      concentration-dependent inhibition was found for the low-affinity transport, but
      no distinct order of potency was identified. Analysis according to Lineweaver-
      Burk of active [(3)H]3',5'-cGMP transport (0.2--2 microM) gave a K(m) value of
      1.5 +/- 0.1 microM (mean +/- SEM, N = 3). The presence of 10 microM cGMP
      analogues did not change the ordinate intercept, but made the slopes steeper with
      a typical order: Rp-cGMPS > 3',5'-cGMP > N-mb-cGMP approximately O-mb-cGMP
      approximately db-cGMP approximately 8-Br-cGMP > 2',3'-cGMP > Sp-cGMPS. Only 3',5'
      cGMP and 2',3'-cGMP were able to activate the cGMP-specific ATPase, 640 +/- 200%
      and 430 +/- 160% (mean +/- SEM, N = 5) above basal levels, respectively. The
      present data show that the binding is less selective than ATPase activation of
      the cellular cGMP transport system.

PMID- 11448452
TI  - Agonist-induced functional desensitization of recombinant human 5-HT2 receptors
      expressed in CHO-K1 cells.
AB  - The desensitization characteristics of recombinant human 5-HT(2A), 5-HT(2B), and
      5-HT(2C) receptors (VSV and INI isoforms) stably expressed in CHO-K1 (Chinese
      hamster ovary) cells was investigated by calcium fluorimetry. Comparative
      desensitization characteristics of the agonists 5-HT, m-chlorophenylpiperazine
      (mCPP), and 2,5-dimethoxy-4-iodoamphetamine hydrobromide (DOI) were performed.
      Human 5-HT(2C (INI)) receptors exhibited a greater degree of desensitization to
      all agonists tested than edited 5-HT(2C (VSV)) receptors. A 2-hr exposure to 5-HT
      resulted in a significantly larger reduction in response upon re-exposure to 5-HT
      at 5-HT(2C (INI)) receptors, as compared to 5-HT(2C (VSV)) receptors (72% and 47%
      respectively, P < 0.01). Both receptor isoforms were expressed at similar
      densities. Human 5-HT(2B) receptors exhibited the most dramatic degree of
      desensitization, with prior exposure to 5-HT reducing subsequent response to 5-HT
      by 80%, with an extremely rapid time-course (t(1/2) < 5 min). The response at 5
      HT(2A) receptors was reduced by 54%. The partial agonists mCPP and DOI also
      elicited desensitization, generally in line with their relative efficacies at
      each receptor, but exhibited more rapid kinetic profiles than 5-HT. Heterologous
      desensitization of an endogenously expressed G(q/11)-coupled purinergic receptor
      was also examined following preincubation of the cell lines with 10 microM 5-HT.
      Only stimulation of 5-HT(2C (VSV)) receptors resulted in a profound attenuation
      of subsequent ATP mediated responses. These results demonstrate differing degrees
      of both homologous and heterologous desensitization of 5-HT(2) receptors.
      Additionally, the different desensitization profiles of 5-HT(2C (INI)) and 5
      HT(2C (VSV)) receptor may be due to signal transduction differences caused by RNA
      editing.

PMID- 11448453
TI  - Effect of metformin on fatty acid and glucose metabolism in freshly isolated
      hepatocytes and on specific gene expression in cultured hepatocytes.
AB  - The short-term effect of metformin on fatty acid and glucose metabolism was
      studied in freshly incubated hepatocytes from 24-hr starved rats. Metformin (5 or
      50 mM) had no effect on oleate or octanoate oxidation rates (CO(2)+ acid-soluble
      products), whatever the concentration used. Similarly, metformin had no effect on
      oleate esterification (triglycerides and phospholipid synthesis) regardless of
      whether the hepatocytes were isolated from starved (low esterification rates) or
      fed rats (high esterification rates). In contrast, metformin markedly reduced the
      rates of glucose production from lactate/pyruvate, alanine, dihydroxyacetone, and
      galactose. Using crossover plot experiments, it was shown that the main effect of
      metformin on hepatic gluconeogenesis was located upstream of the formation of
      dihydroxyacetone phosphate. Increasing the time of exposure to metformin (24 hr
      instead of 1 hr) led to significant changes in the expression of genes involved
      in glucose and fatty acid metabolism. Indeed, when hepatocytes were cultured in
      the presence of 50 to 500 microM metformin, the expression of genes encoding
      regulatory proteins of fatty acid oxidation (carnitine palmitoyltransferase I),
      ketogenesis (mitochondrial hydroxymethylgltaryl-CoA synthase), and
      gluconeogenesis (glucose 6-phosphatase, phosphoenolpyruvate carboxykinase) was
      decreased by 30 to 60%, whereas expression of genes encoding regulatory proteins
      involved in glycolysis (glucokinase and liver-type pyruvate kinase) was increased
      by 250%. In conclusion, this work suggests that metformin could reduce hepatic
      glucose production through short-term (metabolic) and long-term (genic) effects.

PMID- 11448454
TI  - mu Opioid receptor-mediated G-protein activation by heroin metabolites: evidence
      for greater efficacy of 6-monoacetylmorphine compared with morphine.
AB  - The efficacy of heroin metabolites for the stimulation of mu opioid receptor
      mediated G-protein activation was investigated using agonist-stimulated
      [(35)S]guanosine-5'-O-(gamma-thio)-triphosphate binding. In rat thalamic
      membranes, heroin and its primary metabolite, 6-monoacetylmorphine (6-MAM), were
      more efficacious than morphine or morphine-6-beta D-glucuronide. This increased
      efficacy was not due to increased action of heroin and 6-MAM at delta receptors,
      as determined by competitive antagonism by naloxone, lack of antagonism by
      naltrindole, and competitive partial antagonism with morphine. In agreement with
      this interpretation, the same relative efficacy profile of heroin and its
      metabolites was observed at the cloned human mu opioid receptor expressed in C6
      glioma cells. Moreover, these efficacy differences were GDP-dependent in a manner
      consistent with accepted mechanisms of receptor-mediated G-protein activation.
      The activity of heroin was attributed to in vitro deacetylation to 6-MAM, as
      confirmed by HPLC analysis. These results indicate that the heroin metabolite 6
      MAM possesses higher efficacy than other heroin metabolites at mu opioid
      receptors, which may contribute to the higher efficacy of heroin compared with
      morphine in certain behavioral paradigms in vivo.

PMID- 11448455
TI  - Effect of lipopolysaccharide (LPS)-evoked host defense activation on hepatic
      microsomal formation and reduction of sulfamethoxazole hydroxylamine in the rat.
AB  - The incidence of adverse reactions to sulfamethoxazole-trimethoprim (SMX-TMP)
      combination products is higher in patients with AIDS than in the general
      population. Idiosyncratic adverse reactions to SMX are believed to be dependent
      upon the formation of the reactive intermediate, sulfamethoxazole hydroxylamine
      (SMX-HA), and its further oxidation product, nitroso-SMX. Changes in the
      disposition of SMX have been proposed to contribute to the increased risk of SMX
      adverse reactions in patients with AIDS. Activation of host defense mechanisms is
      known to alter drug metabolism and could decrease the enzymatic reduction of SMX
      HA to the parent SMX, causing an imbalance in bioactivation and detoxification.
      We tested this hypothesis in a rat model of lipopolysaccharide (LPS)-evoked host
      defense activation. Rats were treated i.p. with 1 mg/kg of LPS, and hepatic
      microsomes were isolated 24 hr after treatment. The bioactivation of SMX to SMX
      HA was reduced 50% by pretreatment with LPS (113 +/- 10 vs 65 +/- 4 pmol/min/mg;
      P < 0.05). However, the NADH-dependent reduction of SMX-HA to SMX was reduced by
      over 80% (454 +/- 90 vs 81 +/- 48 pmol/min/mg; P < 0.05). A decreased ability to
      reduce SMX-HA to SMX could predispose patients with systemic activation of host
      defense mechanisms, such as those with AIDS, to the occurrence of SMX-associated
      adverse reactions.

PMID- 11448456
TI  - Involvement of NADPH: cytochrome P450 reductase in the activation of
      indoloquinone EO9 to free radical and DNA damaging species.
AB  - Evidence suggests that DT-diaphorase is involved in the activation and mechanism
      of cytotoxicity of the investigational indoloquinone anticancer drug EO9 under
      aerobic conditions. Data also implicate a role for other enzymes including NADPH:
      cytochrome P450 reductase, especially in low DT-diaphorase tumour cells and under
      hypoxic conditions. Here, we used purified rat NADPH: cytochrome P450 reductase
      to provide additional evidence in support of a role for this enzyme in activation
      of EO9 to generate free radical and DNA-damaging species. Electron spin resonance
      spectrometry studies showed that NADPH: cytochrome P450 reductase reduced EO9 to
      a free radical species, including a drug radical (most likely the semiquinone)
      and reactive oxygen species. Plasmid DNA experiments showed that reduction of EO9
      catalysed by NADPH: cytochrome P450 reductase results in single-strand breaks in
      DNA. The information obtained may contribute to the understanding of the
      molecular mechanism of DNA damage and cytotoxicity exerted by EO9 and may be
      useful in the design of future bioreductive drugs.

PMID- 11448457
TI  - Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate
      cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component,
      oleandrin.
AB  - Anvirzel is an extract of Nerium oleander currently undergoing Phase I clinical
      evaluation as a potential treatment for cancer. Two of the active components of
      Anvirzel are the cardiac glycosides oleandrin and oleandrigenin. Previous studies
      have demonstrated that, in vitro, cardiac glycosides may inhibit fibroblast
      growth factor-2 (FGF-2) export through membrane interaction with the Na(+),K(+)
      ATPase pump. In continuing research on the antitumor activity of this novel plant
      extract, the relative abilities of oleandrin and oleandrigenin to inhibit FGF-2
      export from two human prostate cancer cell lines, DU145 and PC3, were examined.
      An ELISA assay was utilized to determine the FGF-2 concentration in the cell
      culture medium before and after exposure to cardiac glycosides or the parent
      extract material Anvirzel. Both cell lines were exposed to non-cytotoxic
      concentrations of oleandrin (0.05 and 0.1 ng/mL) for up to 72 hr. Studies also
      were conducted with Anvirzel and ouabain. Oleandrin (0.1 ng/mL) produced a 45.7%
      inhibition of FGF-2 release from PC3 cells and a 49.9% inhibition from DU145
      cells. Non-cytotoxic concentrations (100 ng/mL) of Anvirzel produced a 51.9 and
      30.8% inhibition of FGF-2 release, respectively, in the two cell lines. The
      decrease in FGF-2 release from cells required continuous incubation for 48--72
      hr; shorter incubation times were not effective. These results demonstrate that
      Anvirzel, like oleandrin, inhibited FGF-2 export in vitro from PC3 and DU145
      prostate cancer cells in a concentration- and time-dependent fashion and may,
      therefore, contribute to the antitumor activity of this novel treatment for
      cancer.

PMID- 11448458
TI  - 6-hydroxydopamine-induced nuclear factor-kappa B activation in PC12 cells.
AB  - The involvement of nuclear Factor-kappa B (NF-kappa B) transcription factor in
      PC12 cell death triggered by the dopaminergic neurotoxin 6-hydroxydopamine (6
      OHDA) was investigated. Results show that oxidative stress generated by 6-OHDA
      activates NF-kappa B. When the NF-kappa B activation was inhibited by
      parthenolide, PC12 cell death induced by 6-OHDA was significantly increased, thus
      suggesting an involvement of this transcription factor in a protective mechanism
      against 6-OHDA toxicity. To further assess this hypothesis, we studied the
      involvement of NF-kappa B in the protective effect of two anti-apoptotic genes,
      bcl-2 and bfl-1. Although Bcl-2 and Bfl-1 expression normally protects PC12 cells
      from 6-OHDA, parthenolide strongly decreased the beneficial effects afforded by
      transgene expression. These results suggest: (1) that the transcription factor NF
      kappa B is likely associated with the protection of catecholaminergic PC12 cells
      and (2) that the protective effects afforded by bcl-2 and bfl-1 expression may be
      dependent on NF-kappa activation.

PMID- 11448459
TI  - Inhibition of stress-activated protein kinase in the ischemic/reperfused heart:
      role of magnesium tanshinoate B in preventing apoptosis.
AB  - The activation of stress-activated protein (SAP) kinase may lead to an induction
      of apoptosis that is responsible for part of the cardiomyocyte death in
      reperfusion injury. The objective of the present study was to investigate the
      mechanism by which magnesium tanshinoate B (MTB), a bioactive compound isolated
      from Danshen, prevents apoptosis in cardiomyocytes in the ischemic/reperfused
      heart. Isolated adult rat hearts were perfused by the Langendorff mode with
      medium containing MTB prior to the induction of normothermic global ischemia. At
      the end of the 30-min ischemic period, the heart was reperfused with the same
      medium with or without MTB for an additional 20 min. In the MTB-treated
      ischemic/reperfused heart, the number of apoptotic nuclei was reduced by 2.5-fold
      in comparison to that in untreated ischemic/reperfused controls [23 +/- 4 vs 57
      +/- 7 (mean +/- SD) TUNEL-positive cells, respectively, N = 3-4, P < 0.001]. SAP
      kinase activity was elevated 1.7-fold in ischemic/reperfused rat hearts [35.6 +/-
      3.8 vs 21.2 +/- 3.3 (control) (mean +/- SEM) relative densitometric units, N = 4
      6, P < 0.05]. Treatment with MTB abolished this elevation in SAP kinase activity
      (25.0 +/- 5.2 relative densitometric units), which was also decreased by 40% in
      the nucleus. When the heart was subjected to ischemia alone, there was no
      significant change in SAP kinase activity in the presence or absence of MTB. MTB
      did not appear to affect the p38 mitogen-activated protein kinase activity in
      this model system. In conclusion, MTB was shown to have cardioprotective activity
      against apoptosis, probably through the inhibition of SAP kinase activity.

PMID- 11448460
TI  - Regulatory roles of adenylate cyclase and cyclic nucleotide phosphodiesterases 1
      and 4 in interleukin-13 production by activated human T cells.
AB  - We studied the activities of 3',5'-adenosine-cyclic monophosphate (cAMP)-
      synthesizing adenylate cyclase (AC) and cAMP-hydrolyzing cyclic nucleotide
      phosphodiesterase (PDE) in phytohemagglutinin (PHA)- or anti-CD3 plus anti-CD28
      stimulated human T cells, and examined their roles in interleukin-13 (IL-13)
      production. The AC inhibitor MDL 12,330A [cis-N-(2
      phenylcyclopentyl)azacyclotridec-1-en-2-amine hydrochloride] completely blocked
      PHA- or anti-CD3/CD28-induced IL-13 production. The PDE 1 inhibitor 8
      methoxymethyl-3-isobutyl-1-methylxanthine or the PDE4 inhibitor rolipram
      partially inhibited IL-13 production, and the addition of both resulted in 100 or
      85% inhibition in PHA- or anti-CD3/CD28-stimulated T cells, respectively. AC in T
      cells was transiently activated 5 min after stimuli, followed by the transient
      activation of PDE4 at 30 min. PDE1 activity, undetectable in resting T cells, was
      detected 3 hr after stimuli, and then increased gradually. Although PDE1-, 2-, 3
      , and 4-independent PDE activity was low (< or = 15% of total), it began to
      increase 3 hr after anti-CD3/CD28; the increase was blocked by PDE7 antisense
      oligonucleotide, and such an increase was not induced by PHA. PHA or anti
      CD3/CD28 induced PDE1B mRNA expression, undetectable in resting T cells. PDE4
      mRNA level in T cells was not altered by either stimulus. PDE7 mRNA expression
      was detected in resting T cells, and was enhanced by anti-CD3/CD28, but not by
      PHA. The cAMP level of T cells increased 5 min after stimuli, returned to the
      basal level at 2 hr, and then continued to decrease. These results suggest that
      PHA or anti-CD3/CD28 initially (< or = 5 min) increases cAMP in T cells via AC,
      then reverses the increase via PDE4 (< or = 2 hr), and in the later phase (> 2
      hr) further decreases cAMP via PDE1. Both the time-dependent increase and
      decrease of cAMP may be required for IL-13 production.

PMID- 11448461
TI  - Attenuation of liver normothermic ischemia--reperfusion injury by preservation of
      mitochondrial functions with S-15176, a potent trimetazidine derivative.
AB  - We investigated the antiischemic properties of a new compound, S-15176, in an
      experimental model of rat liver subjected to 120-min normothermic ischemia
      followed by 30-min reperfusion. Rats were divided into groups, pretreated with
      different doses of S-15176 (1.25, 2.5, 5 and 10 mg/kg/day by intramuscular
      injection) or solvent alone, and subjected to the ischemia--reperfusion process.
      Another group served as the sham-operated controls. Ischemia--reperfusion induced
      huge alterations of hepatocyte functions, namely, a decrease in ATP content and
      bile flow, and membrane leakage of alanine aminotransferase (ALAT) and aspartate
      aminotransferase (ASAT). These effects were associated with alterations in
      mitochondrial functions characterized by (1) a decrease in ATP synthesis, (2) a
      decrease in NAD(P)H levels and mitochondrial membrane potential, and (3) an
      increase in mitochondrial swelling reflecting the generation of permeability
      transition. Pretreatment of rats with S-15176 alleviated these deleterious
      ischemia--reperfusion effects at both the cellular and mitochondrial levels in a
      dose-dependent manner. The protection of mitochondrial functions was almost
      complete at a dosage of 10 mg/kg/day. In addition, in vitro, S-15176 totally
      abolished the swelling of isolated mitochondria induced by a calcium overload
      with an IC(50) value of 10 microM. These data demonstrate that S-15176 protects
      mitochondria against the deleterious effects of ischemia-reperfusion and suggest
      that this protective effect could be related to the inhibition of the
      mitochondrial permeability transition.

PMID- 11448462
TI  - Non-surgical female sterilization with quinacrine: an update.
AB  - The intrauterine installation of quinacrine represents a simple, inexpensive,
      effective, and seemingly safe method of non-surgical female sterilization.
      Existing clinical data on its use are very encouraging: Results of a large study
      conducted in Vietnam with an overall sample of over 30,000 women showed high
      effectiveness; in addition, when a retrospective study was conducted in these
      women, cumulative 5-year pregnancy rates were estimated to be 13% in women
      younger than 35 years and 6.8% in the women older than 35. Overall, failure rates
      with quinacrine have been estimated, at 10 years, to be between 1.9 and 4 times
      higher than those obtainable with conventional surgical procedures of tubal
      interruption. Unfortunately, existing toxicology for topical use of quinacrine
      pellets is incomplete. This prompted an expert group convened by WHO, to comment,
      in 1994, that the toxicology of locally applied quinacrine is inadequate. To
      counter this statement the proponents of the method argue that it is unfair to
      apply the stringent pre-clinical requirements that are mandatory in the
      industrialized world, to methods utilized in countries plagued by both high
      fertility and high maternal mortality. This controversy will soon be resolved
      since conventional toxicological evaluation is now underway. In conclusion, the
      future of quinacrine for non-surgical female sterilization will depend on the
      results of long-term animal studies, as well as the retrospective human studies
      now being carried out.

PMID- 11448463
TI  - First trimester abortion with mifepristone and vaginal misoprostol.
AB  - This study assessed the efficacy and side effects of first trimester medical
      abortion using mifepristone and vaginally administered misoprostol. Medical
      abortion was first introduced in Denmark in December 1997, and the acceptability
      of this new approach in a Danish population was evaluated. The study included the
      first 100 women seeking medical abortion. The gestational age was from 33 to 56
      days. All received 600 mg mifepristone (RU 486) orally followed 2 days later by
      vaginally administered misoprostol 400 microg. Success was defined as achieving
      complete abortion without the need for surgical evacuation. Ninety-three percent
      achieved a successful medical termination of pregnancy. Side effects were few,
      and the acceptability was high. Ninety percent of the women would prefer medical
      abortion in case of a new unwanted pregnancy. The combination of mifepristone and
      vaginally administrated misoprostol is effective, safe, has few side effects and
      is well accepted by Danish women.

PMID- 11448464
TI  - Mifepristone and misoprostol for early abortion when no gestational sac is
      present.
AB  - The study was conducted to determine whether the administration of mifepristone
      followed by vaginal misoprostol can induce an abortion in early pregnancy when no
      gestational sac is present on sonogram. This report presents a prospective, pilot
      study of 30 healthy adult women, pregnant and seeking an abortion, and with no
      gestational sac on sonogram. All women had a baseline serum chorionic
      gonadotropin (hCG) level measured prior to using mifepristone 200 mg orally
      followed by misoprostol 800 mcg vaginally 48 h later, and then returned up to 4
      days later for a repeat sonogram and serum hCG level. Women with initial hCG
      levels > 2000 IU/L were evaluated for ectopic pregnancy. At the first follow-up
      visit, if the hCG decreased by >50%, the women were followed with home pregnancy
      (25 IU/L) tests weekly until negative. If the levels did not decrease by 50%, a
      second dose of misoprostol was given. Surgical intervention was indicated for
      persistent hCG levels or excessive bleeding. Of the 30 women enrolled, the mean
      number of days of amenorrhea was 40 (SD 9) days. Two women had surgical
      intervention for continuing pregnancy, 2 had ectopic pregnancies, and 1 was lost
      to follow-up. Complete medical abortions occurred in 25/30 (88%) women, but when
      recalculated, in 25/27 (93%) women who completed the protocol and who did not
      have an ectopic pregnancy. There was 1 adverse event in a woman with an ongoing
      pregnancy who then received methotrexate. She was hospitalized a day later with a
      complicated pelvic infection and likely methotrexate-induced pneumonitis. Twenty
      three women had a decrease in hCG at first follow-up visit of >50%. All 27 women
      who completed the protocol found the overall regimen acceptable. Mifepristone
      followed at 48 h by vaginal misoprostol were effective and acceptable in inducing
      an abortion in very early pregnancy. There may be a higher incidence of failure
      in very early pregnancies. Documentation of a complete abortion by hCG level is
      necessary to ensure the pregnancy is neither ongoing nor ectopic.

PMID- 11448465
TI  - Serum beta-human chorionic gonadotropin levels and endometrial thickness after
      medical abortion.

PMID- 11448466
TI  - Ovarian function during use of vaginal rings delivering three different doses of
      Nestorone.
AB  - Contraceptive vaginal rings delivering various progestins alone or in combination
      with estrogen have been previously studied, showing adequate steroid vaginal
      absorption and acceptability by the users. Nestorone progestin (NES) is a potent
      19-nor-progesterone derivative, inactive by the oral route, but an excellent
      option for vaginal delivery. The purpose of this study was to evaluate ovarian
      function during 6 months of continuous use of progestin-only vaginal rings
      delivering 3 different doses of NES: 50, 75, and 100 microg per day. Blood
      samples were taken twice a week for 5 consecutive weeks during a control cycle
      and on months 1, 3 and 6 of use, for the measurement of estradiol (E2),
      progesterone (P), and NES. A total of 87 volunteers randomly received each of the
      3 doses. After an initial peak, NES serum levels remained fairly constant
      throughout the duration of the study at about 125, 200 and 250 pmol/L,
      respectively, decreasing slightly with time. Luteal activity occurred very rarely
      (1.2-2.6% of sampling periods) with no apparent difference between doses. Low E2
      levels (< or =100 pmol/L) in all samples of a run were rare (5%) and only with
      the high dose ring (100 microg/day). E2 remained within normal levels (101-1500
      pmol/L) in most of the segments studied. We conclude that the 50 and 75
      microg/day NES rings provide adequate ovulation inhibition without
      hypoestrogenism, while the 100 microg/day ring may deliver an unnecessarily high
      dose.

PMID- 11448467
TI  - Carbohydrate metabolism in sickle cell patients using a subdermal implant
      containing nomegestrol acetate (Uniplant).
AB  - Uniplant, a second-generation contraceptive implant, has been demonstrated to
      promote a significant improvement in the overall well-being of women with sickle
      cell anemia. It has been suggested that the discrete increase in blood glucose
      levels observed in Uniplant users could be a contributory factor for clinical
      improvement. Ten healthy sickle cell patients were enrolled in the study. An oral
      glucose tolerance test was performed prior to implant insertion and at 1, 6, and
      12 months of therapy. Blood glucose and insulin were measured before and at 30,
      60, 120, and 180 min after a 75-g glucose load. The glucose and insulin areas
      under the curves were calculated. Fasting glycosylated hemoglobin was also
      measured. No significant changes were observed in glycosylated hemoglobin,
      glucose or insulin. We conclude that Uniplant is a safe contraceptive for sickle
      cell patients.

PMID- 11448468
TI  - Assessing the acceptability, service delivery requirements, and use-effectiveness
      of the diaphragm in Colombia, Philippines, and Turkey.
AB  - The diaphragm is not available in many countries, despite the recommendations of
      numerous authors that it has important advantages as a woman-controlled method
      that offers some protection against sexually transmitted diseases, and one that
      is safe and free of side effects. An interagency team collaborated to introduce
      the diaphragm in Colombia, the Philippines, and Turkey, using the same protocol
      to assess the acceptability, service delivery requirements and use-effectiveness
      of the method. Eighteen public and private sector service delivery sites were
      involved and a total of 550 women were enrolled in the study. Provider training
      aimed to improve the quality of care with which all methods were delivered and
      included counseling about sexuality and reproductive health risks. The cumulative
      12-month pregnancy rate of 10.1 (SE 1.7) per 100 woman-years is on the low end of
      previous studies of the diaphragm, and the 12-month continuation rate (57.2 [SE
      2.4] per 100) compares favorably with that for oral contraceptives and the
      intrauterine device. Focus group discussions conducted with clients and providers
      indicated that the method was an important alternative for some women,
      particularly those who had experienced health problems with other methods or were
      unable to negotiate condom use with their partners. Provider biases diminished as
      they observed the strategic niche that the diaphragm filled for their clients.
      While providing the diaphragm requires training and good client-provider
      interaction, the requirements are consistent with those called for in the
      Programme of Action of the International Conference on Population and Development
      (ICPD, 1994). With proper attention to quality of care, the diaphragm can be
      successfully offered in resource-poor settings.

PMID- 11448469
TI  - Use of contraceptive methods among homeless women for protection against unwanted
      pregnancies and sexually transmitted diseases: prior use and willingness to use
      in the future.
AB  - Lifetime contraceptive use as reported by a representative sample of 764 homeless
      women in Los Angeles was examined overall and for different age and ethnic
      subgroups and contrasted with expressed willingness to use specific methods. Over
      80% of the women reported condom use. However, less than 5% had ever used female
      condoms, although 38% of the overall sample and 73% of the teenagers said they
      were willing to try them. Similar gaps between reported use and endorsement were
      found for other particular methods. Native Americans had relatively low use of
      virtually all contraceptive methods, and over 80% of African-Americans rejected
      implants. Our findings suggest that age-related factors and ethno-cultural
      perceptions may deter some homeless women from using contraception. In any case,
      gaps between realized use and willingness to use may represent missed
      opportunities to prevent the high rates of unintended pregnancies and sexually
      transmitted infections found among homeless women.

PMID- 11448470
TI  - Effects of DL111-IT or combined with RU486 on uterine polyamines biosynthesis in
      rats during early gestation.
AB  - DL111-IT, a non-hormonal contragestional agent, revealed synergistic effects in
      combination with mifepristone (RU486) in some species. The present study was
      undertaken to clarify the role of DL111-IT when used alone or plus RU486 on
      uterine polyamines biosynthesis, histologic alteration of decidual cells, and
      antifertility activity in rats. The levels of polyamines in pregnant rat uterus
      were determined by formed benzoyl chloride derivatives of polyamines for RP-HPLC.
      The results showed that all the treated groups including DL111-IT 2.8 mg. kg(-1).
      d(-1), RU486 3.0 mg. kg(-1). d(-1), and DL111-IT 0.56 mg. kg(-1). d(-1) plus
      RU486 0.6 mg. kg(-1). d(-1) caused 100% early pregnancy arrest. Uterine
      putrescine, spermidine, and spermine levels in comparison with vehicle control
      were declined significantly from d7 of gestation (1 day after treatment) to d9 or
      d14 (3 days or 8 days after treatment) by Duncan's multiple range test, and
      accompanied by histologic alterations, edema, degeneration and dissolution of
      decidual cells with nuclei indefinite in appearance on d8 of gestation (2 days
      after treatment). The combined administration at lower doses caused the most
      injury. The data verified that the decrease in uterine polyamine levels and
      subsequent decidual cells injuries were the critical role of early pregnancy
      arrest induced by DL111-IT or RU486. The two compounds used in combination with
      lower dosages revealed greatly synergistic effects.

PMID- 11448471
TI  - Opposing effects of endothelin-1 on C-type natriuretic peptide actions in rat
      cardiomyocytes.
AB  - C-type natriuretic peptide (CNP) and Endothelin-1 are paracrine peptides with
      opposing vascular and mitogenic actions. In cardiac myocytes, CNP reduced
      contractility and induced accumulation of cyclic guanosine monophosphate (cGMP).
      Endothelin-1 caused an increase in contractile amplitude, abolished the negative
      inotropic effect of CNP, reduced the negative inotropic effect of a membrane
      permeable cGMP, and inhibited cGMP accumulation induced by CNP. We conclude that
      endothelin-1 abolishes the negative inotropic effect of CNP. This effect may be
      mediated by inhibition of the negative inotropic actions of cGMP as well as by
      reduction of cGMP levels.

PMID- 11448472
TI  - Effects of doxorubicinol on excitation--contraction coupling in guinea pig
      ventricular myocytes.
AB  - The cardiotoxicity of the anticancer drug doxorubicin may be related to its main
      metabolite doxorubicinol. In this study, the acute effects of doxorubicinol on
      excitation-contraction coupling in isolated guinea pig ventricular myocytes were
      investigated and compared with doxorubicin using the whole-cell patch-clamp-,
      fura-2 fluorescence- and cell-edge tracking techniques. Both drugs were applied
      intracellularly by diffusion from the patch electrode for 15--20 min. Doxorubicin
      (100 microM) prolonged the action potential duration (APD) by 31% and enhanced
      cell shortening by 26%. Contrary to doxorubicin, doxorubicinol (10 microM)
      shortened APD by 25% and decreased cell shortening by 31%. APD shortening by
      doxorubicinol was due to an increase of the delayed rectifier K(+) current.
      Neither the inward rectifier K(+) current nor the L-type Ca(2+) current was
      influenced by doxorubicinol. The decline in cell shortening induced by
      doxorubicinol was not exclusively due to APD shortening because doxorubicinol
      reduced the peak Ca(2+) transient by 23% in cells clamped with an action
      potential of constant duration. Despite opposite effects on APD and
      contractility, both doxorubicin and doxorubicinol produced a considerable delay
      in the activation and inactivation of contraction and Ca(2+) transient,
      compatible with an impaired function of the sarcoplasmic reticulum. It is
      suggested that doxorubicinol-induced APD shortening may amplify the detrimental
      effects of both doxorubicin and doxorubicinol on sarcoplasmic reticulum Ca(2+)
      load and hence on contractile function. The accumulation of doxorubicinol in the
      cardiac myocytes may play an important role in the time-dependent development of
      doxorubicin-induced ventricular dysfunction.

PMID- 11448473
TI  - Differential [(3)H]idazoxan and [(3)H]2-(2-benzofuranyl)-2-imidazoline (2-BFI)
      binding to imidazoline I(2) receptors in human postmortem frontal cortex.
AB  - [(3)H]2-(2-benzofuranyl)-2-imidazoline (2-BFI) and [(3)H]idazoxan are the most
      used tools to characterise imidazoline I(2) receptors. We evaluated the binding
      of both radioligands to human postmortem frontal cortex membranes. Saturation
      binding analyses revealed that [(3)H]idazoxan (in the presence of 2 microM
      efaroxan to avoid radioligand binding to alpha(2)-adrenoceptors and imidazoline
      I(1) receptors) and [(3)H]2-BFI bound with high affinity to an apparent single
      population of sites. However, in competition studies whereas [(3)H]idazoxan (10
      nM) binding was displaced monophasically by idazoxan and 2-BFI, both drugs
      displayed biphasic curves for [(3)H]2-BFI (1 nM). The proportion of the low
      affinity binding site increased from 17% to 25% when 10 nM [(3)H]2-BFI was
      displaced by idazoxan. Amiloride inhibited [(3)H]2-BFI (10 nM) binding with low
      affinity and in a monophasic way. These data indicate that [(3)H]2-BFI recognises
      in human postmortem brain membranes a second binding site different from the
      imidazoline I(2) receptors labelled by [(3)H]idazoxan.

PMID- 11448474
TI  - beta(1)-Adrenoceptor antibodies induce positive inotropic response in isolated
      cardiomyocytes.
AB  - beta(1)-Adrenoceptor autoantibodies are present in approximately 30% of patients
      suffering from dilated cardiomyopathy. The inotropic effects mediated by these
      antibodies remain to be studied. Monoclonal antibodies were raised against a
      peptide corresponding to the second extracellular loop of the human beta(1)
      adrenoceptor in balb/C mouse (n=6), and were characterized by enzyme immunoassay
      after purification by protein A. Purified immunoglobulin G from non-immunized
      animals (controls) did not influence Ca(2+) transient and cell shortening of rat
      cardiomyocytes measured by confocal-laser-scanning-microscopy. beta(1)
      adrenoceptor antibodies caused a dose-related increase in Ca(2+) transient
      (dilution 1:2: +35.3+/-5.1%), and in cell shortening (dilution 1:2: +40.5+/-6.3%)
      (P<0.01 vs. controls). The effect of the beta(1)-adrenoceptor antibodies was
      blocked by the antigenic peptide and by the antagonist metoprolol. In addition,
      beta(1)-adrenoceptor antibodies induced a dose-dependent increase of the cyclic
      adenosine monophosphate. The inotropic response induced by isoproterenol was
      attenuated by the beta(1)-adrenoceptor antibody. beta(1)-adrenoceptor antibodies
      as partial agonists induce a specific positive inotropic effect via the protein
      kinase-A-cascade.

PMID- 11448475
TI  - Temperature-dependent activation of recombinant rat vanilloid VR1 receptors
      expressed in HEK293 cells by capsaicin and anandamide.
AB  - Capsaicin activates vanilloid (VR1) receptors found on sensory neurons. These
      ligand-gated ion channels are also sensitive to low pH, elevated temperature and
      the endocannabinoid, anandamide. In this study, we have measured capsaicin- and
      anandamide-induced elevations in intracellular calcium concentrations
      ([Ca(2+)](i)) in fura-2 loaded HEK293 cells stably expressing the rat VR1
      receptor at 22, 37 and 50 degrees C. Both capsaicin and anandamide produced a
      concentration-dependent elevation in [Ca(2+)](i) at all temperatures. pEC(50)
      values were 7.74 and 5.69 at 22 degrees C and 6.90 and 5.15 at 37 degrees C for
      capsaicin and anandamide, respectively. At 50 degrees C, the pEC(50) value for
      capsaicin was 6.36 but the response to anandamide did not saturate. Responses to
      both agonists were sensitive to ruthenium red and capsazepine at all
      temperatures. This temperature-dependent reduction in potency may result from
      desensitization.

PMID- 11448476
TI  - In vivo and in vitro influence of etretinate on erythrocyte membrane fluidity.
AB  - The molecular mechanisms underlying the action of synthetic retinoids have been
      studied intensively, but they are not fully understood yet. It is well known that
      retinoids exert their effects on gene expression via the retinoic acid receptor.
      Some observations suggest that the main aromatic retinoid etretinate (Tigason)
      exerts its therapeutic effect in psoriasis also through an action on the cell
      membrane. In this paper, we present the results of previously unreleased
      experiments (when Tigason was still in use) concerning the in vivo and in vitro
      influence of etretinate on erythrocyte membrane fluidity in psoriatic patients.
      Erythrocytes from healthy subjects and topically treated psoriatics were chosen
      as control groups. Membrane fluidity was measured by the electron paramagnetic
      resonance (EPR) spin-labelling technique. Erythrocytes from psoriatic patients
      had lower membrane fluidity, a lower antioxidant activity and a greater
      susceptibility to peroxidation than those from healthy subjects. After treatment
      with etretinate, a significant increase in erythrocyte membrane fluidity and in
      antioxidant activity as well as a decrease in lipid peroxidation were observed in
      erythrocytes from patients. Local therapy of psoriatic lesions had no influence
      on the improvement in membrane fluidity and antioxidant activity of erythrocytes.
      Incubation of erythrocytes from healthy controls and topically treated psoriatics
      with etretinate in vitro confirmed its fluidizing effect on erythrocyte
      membranes. These data may indicate that two mechanisms lead to an increase in
      erythrocyte membrane fluidity in psoriatic patients treated with Tigason: the
      first one, indirect, by improvement of the antioxidant defence system and cell
      protection against lipid peroxidation, and the second one, by a direct fluidizing
      effect of etretinate on the erythrocyte membrane.

PMID- 11448477
TI  - Biphasic response to human galanin of extracellular acidification in human Bowes
      melanoma cells.
AB  - The metabolic response of galanin GAL1 receptor subtype, endogenously expressed
      in human Bowes melanoma (HBM) cells, was investigated. Cytosensor
      microphysiometry was used to determine the extracellular acidification rate. A
      biphasic response, consisting of a rapid increase in the extracellular
      acidification rate followed by a decrease below the basal level, was observed
      after perfusion with human galanin. The magnitude and the rate of onset of both
      phases were dependent on the galanin concentration. The increase in the
      extracellular acidification rate (maximum of 25% of basal level; 
      log(EC(50))=7.23+/-0.14) was transient, whereas the following decrease (maximum
      of 40% of basal level; -log(EC(50))=7.77+/-0.23) was sustained. The EC(50) values
      for the increase and decrease were in a similar range. After consecutive galanin
      administration, the magnitude of the response was the same as for the unexposed
      cells, indicating the absence of galanin receptor desensitization or
      internalization in HBM cells. Responses were blocked by pretreatment with
      pertussis toxin and phorbol-12-myristate-13-acetate (PMA), indicating a G
      protein/protein kinase C signalling pathway. Our microphysiometry results show a
      biphasic response of the extracellular acidification rate mediated by the galanin
      receptor expressed in HBM cells which has not been described previously for any
      other endogenously expressed neuropeptide receptor.

PMID- 11448478
TI  - Direct evidence for the interaction of neurokinin A with the tachykinin NK(1)
      receptor in tissue.
AB  - Neurokinin A (NKA) is a tachykinin peptide that binds with high affinity to the
      tachykinin NK(2) receptor. Recent homologous binding studies, however, have shown
      that neurokinin A is also a high-affinity ligand for the tachykinin NK(1)
      receptor. In this report, we demonstrate that a photoreactive neurokinin A
      analogue specifically labels the NK(1) receptor in rat submandibular gland
      membranes and show via bioassay that neurokinin A is a potent stimulator of
      salivary secretion. Through the use of specific non-peptide antagonists in both
      photolabeling and functional assays, we unequivocally demonstrate that neurokinin
      A can specifically interact with the NK(1) receptor in vivo and elicit NK(1)
      receptor-mediated physiological responses.

PMID- 11448479
TI  - Nicotinic receptors involved in gastric noradrenaline release evoked by
      electrical stimulation of the splanchnic nerve in rats.
AB  - In the present experiment, we tried to compare the functional nicotinic receptors
      activated by electrical stimulation of the greater splanchnic nerve (containing
      preganglionic sympathetic nerves) to those activated by (-)-nicotine, using the
      isolated rat stomach. The stomach was perfused with Krebs-Ringer solution and
      endogenous noradrenaline released into the perfusate was electrochemically
      measured using high-performance liquid chromatography. The release of
      noradrenaline evoked by repeated application of 30 mM (-)-nicotine rapidly
      declined. However, the release of noradrenaline evoked by electrical stimulation
      of the splanchnic nerve at 2.5 Hz was not disturbed by the appearance of
      tachyphylaxis for (-)-nicotine. The (-)-nicotine-induced release of noradrenaline
      was abolished by diltiazem, but this reagent had no effect on the electrically
      evoked release of noradrenaline. The electrically evoked release of noradrenaline
      was not influenced by atropine, but was reduced to approximately 50% by
      hexamethonium. This electrically evoked release of noradrenaline was not
      influenced by alpha-bungarotoxin, alpha-conotoxin ImI (blockers of alpha 7
      nicotinic receptors) or dihydro-beta-erythroidine (a blocker of alpha 4 beta 2
      nicotinic receptors), but was reduced to about 50% by mecamylamine (a blocker of
      alpha 3 beta 4 nicotinic receptors). The (-)-nicotine-induced release of
      noradrenaline has already been shown to be partially blocked by dihydro-beta
      erythroidine and to be abolished by mecamylamine as shown by Yokotani et al.
      [Eur. J. Pharmacol. 402 (2000) 223.]. These results suggest that the gastric
      release of noradrenaline in response to electrical stimulation of the greater
      splanchnic nerve is mediated by cholinergic (probably ganglionic alpha 3 beta 4
      nicotinic receptor-mediated) and non-cholinergic mechanisms in rats. However, the
      functional nicotinic receptor activated by electrical stimulation of the
      splanchnic nerve seems to be different in character from that activated by (-)
      nicotine.

PMID- 11448480
TI  - Tolerance to analgesia and dependence liability by topical application of
      dihydroetorphine to hairless rats.
AB  - The tolerance to analgesia and dependence liability of dihydroetorphine following
      topical application were investigated in hairless rats with and without formalin
      induced inflammation. The analgesic effect of dihydroetorphine (s.c.) was 4600-
      to 7200-fold more potent than that of morphine. In non-inflamed rats, the
      analgesic effect of 24-h topical application of dihydroetorphine tape (35 microg)
      and 4-day repeated tape applications (20 microg/5 h/day) decreased with time
      after the start of application, even though the plasma dihydroetorphine
      concentrations did not decrease. In formalin-inflamed rats, however, the
      tolerance to analgesia diminished. Naloxone-precipitated weight loss was observed
      after 24-h infusion of dihydroetorphine but not after the tape application in non
      inflamed rats. A significant rewarding effect was found in the non-inflamed rats
      conditioned by s.c. injection and tape application but not in the formalin
      inflamed rats. These results indicate that topical application of
      dihydroetorphine has a tolerance and dependence liability when there is no pain,
      and therefore, it should be used only for pain relief.

PMID- 11448481
TI  - Effects of vasopressin on histamine H(1) receptor antagonist-induced spatial
      memory deficits in rats.
AB  - The effects of [Arg(8)] vasopressin on histamine H(1) receptor antagonist-induced
      memory deficits were investigated using the eight-arm radial maze performance
      test in rats. Pyrilamine and diphenhydramine as well as scopolamine induced
      memory deficits characterized by increases in the number of total errors,
      reference memory errors and working memory errors. [Arg(8)] vasopressin improved
      not only scopolamine--but also pyrilamine--and diphenhydramine-induced memory
      deficits, although a high dose of [Arg(8)] vasopressin was needed to antagonize
      pyrilamine-induced memory deficits. The effects of pyrilamine on the brain
      [Arg(8)] vasopressin content were studied, and the hippocampus [Arg(8)]
      vasopressin content was shown to be decreased after pyrilamine injection. From
      these observations, it seems likely that [Arg(8)] vasopressin participates in not
      only the cholinergic system but also the histaminergic system in spatial memory.

PMID- 11448482
TI  - Ventral striatal vs. accumbal (shell) mechanisms and non-cyclase-coupled dopamine
      D(1)-like receptors in jaw movements.
AB  - This study compared the effects of intracerebral injections of the dopamine D(1)
      like receptor agents 3-methyl-6-chloro-7,8-dihydroxy-1-[3-methylphenyl]-2,3,4,5
      tetrahydro-1H-3-benzazepine (SK&F 83959) and [R]-3-methyl-7-chloro-8-hydroxy-1
      phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) into the ventrolateral
      striatum or the shell of the nucleus accumbens on the synergistic induction of
      jaw movements by intravenous (i.v.) co-administration of [R]-7,8-dihydroxy-1
      phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 38393) or SK&F 83959 with the
      dopamine D(2)-like receptor agonist, quinpirole. In the ventrolateral striatum,
      SCH 23390 and SK&F 83959 each blocked jaw movements induced by i.v. SK&F 38393
      with quinpirole, while only SCH 23390 blocked i.v. SK&F 83959 with quinpirole.
      SCH 23390 was less effective in the accumbens shell than in the ventrolateral
      striatum, and SK&F 83959 was ineffective to block i.v. SK&F 38393 with
      quinpirole, while neither SCH 23390 nor SK&F 83959 blocked i.v. SK&F 83959 with
      quinpirole. As SK&F 83959 inhibits the stimulation of adenylyl cyclase via
      dopamine D(1A) receptors but acts as an agonist at a putative dopamine D(1)-like
      receptor site not linked to cyclase, an important role is indicated for non
      cyclase-coupled dopamine D(1)-like receptor sites as well as dopamine D(1A)
      receptors in the regulation of jaw movements via dopamine D(1)-like/D(2)-like
      receptor synergism, particularly in the ventrolateral striatum.

PMID- 11448483
TI  - Relatively selective neuronal nitric oxide synthase inhibition by 7-nitroindazole
      in monkey isolated cerebral arteries.
AB  - The selectivity of 7-nitroindazole in inhibiting endothelial and neuronal nitric
      oxide synthases (eNOS and nNOS) was investigated by comparing its inhibitory
      action on relaxations mediated by nitric oxide (NO) in response to stimulation of
      perivascular nerves and in response to histamine in monkey cerebral artery
      strips. 7-Nitroindazole at 2 x 10(-5) M moderately attenuated the response to
      transmural electrical stimulation and to nicotine, but did to alter the
      endothelium-dependent relaxation in response to histamine in cimetidine-treated
      strips. Raising the concentration of 7-nitroindazole to 10(-4) M abolished the
      neurogenic response, partially inhibited the histamine-induced relaxation, but
      did not affect the response to NO. It is concluded that 7-nitroindazole is a
      relatively selective nNOS inhibitor; however, at high concentrations, it inhibits
      eNOS in monkey cerebral arteries.

PMID- 11448484
TI  - Mesenteric vascular bed responsiveness in bile duct-ligated rats: roles of opioid
      and nitric oxide systems.
AB  - Changes in vascular responsiveness are proposed as the basis for some of the
      cardiovascular complications in cholestasis. Cholestasis is also associated with
      accumulation of endogenous opioid peptides and evidence of overproduction of
      nitric oxide (NO). The possible role of NO or opioid system in cholestasis
      induced mesenteric vascular bed responsiveness was investigated. Bile duct
      ligated and sham-operated rats were treated for 6 days with either normal saline,
      naltrexone, an opioid antagonist (20 mg/kg/day) or L-NAME (N(omega)-nitro-L
      arginine methyl ester), a nitric oxide synthase inhibitor (3 mg/kg/day). After 7
      days, the superior mesenteric artery was cannulated and the mesenteric vascular
      bed was perfused according to the McGregor method. Baseline perfusion pressure of
      the mesenteric vascular bed was decreased in bile duct-ligated compared to sham
      operated animals. ED(50) of phenylephrine-induced vasoconstriction was increased,
      but vasoconstriction R(max) was not different in the vascular bed of bile duct
      ligated rats and of sham-operated ones. Acetylcholine-induced vasorelaxation was
      impaired in bile duct-ligated rats (increased ED(50) and decreased vasorelaxation
      R(max)). Sodium nitroprusside-induced vasorelaxation was not different between
      bile duct-ligated and sham-operated rats, implying that the smooth muscle
      components of vasorelaxation were intact. Chronic treatment with L-NAME partially
      restored both the acetylcholine-induced vasorelaxation and phenylephrine-induced
      vasoconstriction response in bile duct-ligated rats. Naltrexone treatment also
      partially restored the acetylcholine-induced vasorelaxation and phenylephrine
      induced vasoconstriction in bile duct-ligated rats. There is impaired
      acetylcholine-induced vasorelaxation in cholestatic rats, probably due to a
      defect in endothelial function. This study also provided evidence for the
      involvement of increased opioidergic tone and NO overproduction in cholestasis
      induced vascular hyporesponsiveness.

PMID- 11448485
TI  - Vascular and renal effects of vasopressin and its antagonists in conscious rats
      with chronic myocardial infarction; evidence for receptor shift.
AB  - Acute myocardial infarction evokes activation of, among others, the arginine
      vasopressin system, resulting in vasoconstriction and fluid retention. In the
      present study, the vasoconstrictor and antidiuretic effects of vasopressin were
      examined in vivo in conscious rats with chronic myocardial infarction, in the
      absence or presence of the V(1a) receptor antagonist SR-49059 or the V(2)
      receptor antagonist OPC-31260. In sham rats, vasopressin dose-dependently
      increased mean arterial pressure (maximum response: 45+/-3 mm Hg), which was
      significantly suppressed in infarcted rats (maximum response: 32+/-3 mm Hg). SR
      49059, but not OPC-31260, caused a significant rightward shift of the dose
      pressure response curve in sham rats, indicating V(1a) receptor mediation. This
      rightward shift by SR-49059 was significantly more in infarcted rats. The
      suppressed response to the agonist and enhanced sensitivity to the antagonist
      suggest a reduction of V(1a) receptor number in infarcted rats. In both sham and
      infarcted rats, the urine production after OPC-31260 (337+/-14 and 329+/-30
      microl/min, respectively) was about twice of that in vehicle-treated rats (188+/
      25 and 155+/-24 microl/min, respectively). However, the response in infarcted
      rats reached its peak quicker and lasted for a shorter period, resulting in a 40%
      lower area under the curve. Although only measurable during V(2) receptor
      blockade, the reduction of urine production by vasopressin was significantly more
      in infarcted compared to sham rats. The enhanced renal response to the agonist
      and reduced response to the antagonist suggest an increase in V(2) receptor
      number in infarcted rats. In conclusion, in chronically infarcted rats,
      vasopressin causes vasoconstriction and fluid retention through the V(1a) and
      V(2) receptors, respectively. Altered responses after infarction indicate a shift
      from V(1a) to V(2) receptors.

PMID- 11448486
TI  - Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated
      by cannabinoid CB(1) receptors.
AB  - Activation of peripheral cannabinoid CB(1) receptors elicits hypotension. Using
      the radioactive microsphere technique, we examined the effects of cannabinoids on
      systemic hemodynamics in anesthetized rats. The potent cannabinoid CB(1) receptor
      agonist HU-210 ([-]-11-OH-Delta(9) tetrahydrocannabinol dimethylheptyl, 10
      microg/kg i.v.) reduced mean blood pressure by 57+/-5 mm Hg by decreasing cardiac
      index from 37+/-1 to 23+/-2 ml/min/100 g (P<0.05) without significantly affecting
      systemic vascular resistance index. HU-210 elicited a similar decrease in blood
      pressure following ganglionic blockade and vasopressin infusion. The endogenous
      cannabinoid anandamide (arachidonyl ethanolamide, 4 mg/kg i.v.) decreased blood
      pressure by 40+/-7 mm Hg by reducing systemic vascular resistance index from
      3.3+/-0.1 to 2.3+/-0.1 mm Hg min/ml/100 g (P<0.05), leaving cardiac index and
      stroke volume index unchanged. HU-210, anandamide, and its metabolically stable
      analog, R-methanandamide, lowered vascular resistance primarily in the coronaries
      and the brain. These vasodilator effects remained unchanged when autoregulation
      was prevented by maintaining blood pressure through volume replacement, but were
      prevented by pretreatment with the cannabinoid CB(1) receptor antagonist
      SR141716A (N-[piperidin-1-yl]-5-[4-chlorophenyl]-1-[2,4-dichlorophenyl]-4-methyl
      1H-pyrazole-3-carboxamide HCl; 3 mg/kg i.v.). Only anandamide and R
      methanandamide were vasodilators in the mesentery. We conclude that cannabinoids
      elicit profound coronary and cerebral vasodilation in vivo by direct activation
      of vascular cannabinoid CB(1) receptors, rather than via autoregulation, a
      decrease in sympathetic tone or, in the case of anandamide, the action of a non
      cannabinoid metabolite. Differences between the hemodynamic profile of various
      cannabinoids may reflect quantitative differences in cannabinoid CB(1) receptor
      expression in different tissues and/or the involvement of as-yet-unidentified
      receptors.

PMID- 11448487
TI  - Effect of TNBS-induced morphological changes on pharmacological contractility of
      the rat ileum.
AB  - Intraluminal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in
      ethanol is a classical model of colitis in the rat. Little is known about the
      time-related effect of TNBS on the contractility and morphology of the rat ileum.
      After 36 h, TNBS induced acute ileitis. Spontaneous activity of longitudinal
      muscle strips was decreased, as were receptor- and nonreceptor-mediated
      contractions and contractions induced by electrical stimulation. After 1 week,
      mucosal integrity was restored, although the thickness of both mucosal and muscle
      layers was increased. Spontaneous activity, receptor- and nonreceptor-mediated
      contractions and electrically induced contractions of longitudinal muscle strips
      were increased due to hypertrophy and hyperplasia of smooth muscle cells. This
      was confirmed in the contractility study of individual muscle cells. Functional
      alterations after 1 week were restricted to a decreased response to substance P.
      TNBS-ileitis in the rat lacks a chronic phase and is accompanied by functional
      hypocontractility of longitudinal smooth muscle cells during the acute
      inflammation, whereas the contractility of the longitudinal muscle layer is
      increased in the postinflammation phase due to structural alterations. There is a
      selective inhibition of the response to substance P in the postinflammation
      phase.

PMID- 11448488
TI  - Prejunctional actions of methylenedioxymethamphetamine in vas deferens from wild
      type and alpha(2A/D)-adrenoceptor knockout mice.
AB  - Methylenedioxymethamphetamine (MDMA, 'ecstasy') has major agonist actions at
      prejunctional alpha(2A/D)-adrenoceptors in the rat. We wished to establish
      whether MDMA has potency at more than one subtype of alpha(2)-adrenoceptor, in
      line with affinity in ligand-binding studies. We have investigated the effects of
      MDMA in vas deferens from wild-type and from knockout mice lacking the
      alpha(2A/D)-adrenoceptor. The potency of the alpha(2)-adrenoceptor agonist
      xylazine at inhibiting stimulation-evoked contractions to a single stimulus in
      the presence of cocaine was significantly reduced in knockout (pD(2) of 8.27+/
      0.07, -log M, n=4) as compared with wild-type mice (8.69+/-0.08, n=4, P<0.05),
      whereas potency of MDMA was unchanged (5.39+/-0.06, n=4 versus 5.38+/-0.06, n=6).
      Similar differences between xylazine and MDMA were seen for responses to
      stimulation at 10 Hz for 4 s. In studies of mouse atria pre-incubated with (3)H
      noradrenaline, the stimulation-evoked release of tritium was inhibited to a
      similar extent by MDMA (10 microM) in tissues from wild-type and knockout mice.
      The prejunctional alpha(2A/D)-adrenoceptor is reported to be replaced by the
      alpha(2C)-adrenoceptor in this knockout mouse, so that we have evidence that
      suggests that MDMA has similar potencies at both subtypes in functional studies.

PMID- 11448489
TI  - Vasoactive intestinal peptide protects guinea-pig detrusor nerves from
      anoxia/glucopenia injury.
AB  - Vasoactive intestinal peptide (VIP) was tested for its capability to protect the
      intrinsic nerves of guinea-pig urinary bladder from damage due to
      anoxia/glucopenia and reperfusion. Guinea-pig detrusor strips were mounted for
      tension recording in small organ baths and the nerves were subjected to electric
      field stimulation. VIP (0.3 microM) improved significantly the response of strips
      to electrical field stimulation either during anoxia/glucopenia or thereafter
      during reperfusion, as compared to untreated tissues. The antioxidant activity of
      VIP assessed as its capability to scavenge peroxyl radicals during linoleic acid
      oxidation corresponded to 6.42+/-0.13 pIC(50) M, i.e. close to the concentration
      proved to protect strips against the anoxic--glucopenic and reperfusion damage.

PMID- 11448490
TI  - Differential expression of cannabinoid CB(2) receptor mRNA in mouse immune cell
      subpopulations and following B cell stimulation.
AB  - Cannabinoid CB(2) receptor is reported to be expressed in varying amounts in
      different human immune subpopulations. To examine the expression pattern of CB(2)
      in the mouse, immune cell subpopulations were purified and studied by
      semiquantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR). CB(2)
      mRNA was most abundant in splenic B cells, followed by macrophages and T cells.
      Furthermore, CB(2) was expressed in thioglycollate-elicited peritoneal
      macrophages, but not in resident peritoneal macrophages. In addition to these
      studies on receptor expression at basal activity, CB(2) mRNA expression was also
      studied following immune cell activation. Bacterial lipopolysaccharide
      stimulation downregulated CB(2) mRNA expression in splenocyte cultures in a dose
      response manner, while stimulation through cluster of differentiation 40 (CD40)
      using anti-CD40 antibody upregulated the response and costimulation with
      interleukin-4 attenuated the anti-CD40 response. These results demonstrate that
      CB(2) mRNA expression differs among mouse immune subpopulations similar to what
      is observed in human immune cells. Furthermore, the results suggest that the
      signaling pathways activated by lipopolysaccharide and anti-CD40 might have
      different effects on CB(2) mRNA expression.

PMID- 11448491
TI  - kappa-Opioid receptor agonist-induced prolactin release in primates is blocked by
      dopamine D(2)-like receptor agonists.
AB  - Kappa-opioid receptor agonists may have pharmacotherapeutic potential in the
      management of psychostimulant abuse, due to their ability to modulate dopamine
      receptor systems involved in drug reinforcement. kappa-Opioid receptor agonists
      also modulate dopamine receptor function in the hypothalamic tuberoinfundibular
      system, which has inhibitory control over an anterior pituitary hormone,
      prolactin. Prolactin levels may thus be a "biomarker" for the ability of kappa
      opioid receptor agonists (e.g., (+)-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1
      pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U69,593)) to modulate a
      dopamine receptor system in vivo in primates. The effectiveness of dopamine D(2)
      like receptor agonists (quinpirole and (+/-)-7-hydroxy-dipropylaminotetralin (7
      OH-DPAT); 0.0032-0.1 mg/kg) in preventing U69,593-induced prolactin release was
      studied in intact female rhesus monkeys. Quinpirole and 7-OH-DPAT inhibited
      U69,593-induced prolactin release (ID(50) values: 0.013 and 0.0072 mg/kg,
      respectively). However, the dopamine D(1)-receptor agonist (+/-)-6-chloro-7,8
      dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazapine (SKF 82958; 1
      mg/kg) did not inhibit U69,593-induced prolactin release under the same
      conditions. In contrast, the largest doses of quinpirole or 7-OH-DPAT presently
      studied (0.1 mg/kg), did not decrease sedation caused by U69,593 (0.01, 0.032
      mg/kg), a prominent effect of centrally penetrating kappa-opioid receptor
      agonists. The sedative effect of U69,593 (0.032 mg/kg) was prevented by
      naltrexone (0.32 mg/kg), consistent with kappa-opioid receptor mediation of this
      effect. These studies suggest that prolactin release is a valid biomarker for the
      ability of kappa-opioid receptor agonists to modulate dopamine D(2)-like receptor
      function, and may also be used to quantify dopamine D(2)-like receptor agonist
      potency in primates.

PMID- 11448492
TI  - Associations between oil- and gas-well sites, processing facilities, flaring, and
      beef cattle reproduction and calf mortality in western Canada.
AB  - From the fall of 1992 through calving 1996, detailed cow breeding outcome records
      were maintained actively for seven large cow-calf herds in western Canada. The
      numbers of mature females in the study for the breeding seasons beginning in
      1992, 1993, 1994, and 1995 were 1122, 1177, 1251, and 1236, respectively.
      Outcomes included pregnancy status, calving interval, and the occurrence of
      twins, abortions, stillbirths, and neonatal mortality. Information also was
      collected on other risk factors known to influence beef-herd health and
      productivity. Detailed maps of active and inactive oil and natural-gas sites,
      batteries, compressor stations and processing plants were verified. Records of
      flaring activity at each facility were obtained from the government regulatory
      agency. Each flaring site then was classified as sour or sweet based on the
      presence or absence of hydrogen sulfide in the flared gas. A detailed inventory
      was prepared itemizing the type and number of facilities within 1.6 km (1 mile)
      of the center of each quarter section used for pasture. The total volume of gas
      flared within 1.6 km of the center of each pasture was determined for each month
      of the study. Appropriate risk periods where specified for each outcome and a
      cumulative exposure calculated for each breeding female (using detailed
      individual-animal records of cow movements between pastures and herd-management
      groups). Generalized estimating equations were used to evaluate the association
      between exposure and outcome and to adjust for potential confounders and
      clustering of binomial outcomes within herd. Increased risk of non-pregnancy was
      sometimes associated with exposure to one or more of the following facility
      types: sour-gas flaring battery facilities, all battery-flaring sites, active gas
      wells, and larger field facilities. The associations were not, however,
      consistent among years or even among risk periods for the same year. Facility
      proximity and flaring were not associated with increased abortion risk. Volume of
      flared sour gas from battery sites was associated with increased risk of
      stillbirth. Finally, sour-gas flaring was associated with increased calf
      mortality risk for the 1992-1993 calf crop. Several examples of associations
      between exposure and increased productivity also were found (most of which
      involved either oil wells or all well sites).

PMID- 11448493
TI  - Associations between total sulfation, hydrogen sulfide deposition, and beef
      cattle breeding outcomes in western Canada.
AB  - Beef cows sometimes are pastured close to oil- and gas-production and processing
      facilities. We measured the health and productivity of cow-calf herds with
      differing exposure to sour-natural-gas processing facilities in western Canada.
      In seven cow-calf herds, the numbers of eligible mature females included in the
      study for the breeding seasons beginning in 1993, 1994, and 1995 were 1177, 1251,
      and 1236, respectively. Outcomes included pregnancy status, calving interval, and
      the occurrence of twins, abortions, stillbirths, and neonatal mortality.
      Information also was collected on other risk factors known to influence beef-herd
      health and productivity. Monthly measurements from a network of passive air
      monitoring devices were used to estimate exposure. Total sulfation and H2S
      deposition were used as markers for the complex mixture of compounds found in
      emissions from sour-gas processing plants and sour flares. Most herds were
      managed in multiple pasture groups. Cumulative exposure assessments were made
      from records of individual-animal movements between pastures. Generalized
      estimating equations were used to evaluate the association between exposure and
      outcome and to adjust for potential confounders and clustering of binomial
      outcomes within herd. No consistent associations were found between either total
      sulfation or H2S deposition and productivity parameters across the cow-calf
      production cycles. There were, however, five examples of significant associations
      between increasing cumulative exposure to total sulfation and decreased
      productivity in the 18 models examined.

PMID- 11448494
TI  - Repeatability and validity of a combined mail and telephone questionnaire on
      demographics, diet, exercise and health status in an insured-dog population.
AB  - The validity and repeatability of a telephone questionnaire on demographics,
      diet, living patterns, exercise and health status in a well-defined dog
      population was assessed. Randomly selected dogs aged 1-3 years in the largest
      animal-insurance database of Sweden were included in the study. The repeatability
      was measured by doing two identical interviews with 64 dog owners on average 39
      (S.D. 17) days apart. The overall response percentage was 66% (64/97). The
      repeatabilities for demographic data were excellent (r(sp) 0.82-1.00), and
      dietary intake and feeding patterns correlated well between interviews (r(sp)
      0.66-0.99, kappa 0.57-0.95). However, correlations for the frequency and daily
      intake of specific table foods had a wide range (r(sp) 0.06-0.97). The energy and
      specific nutrient intakes had high repeatabilities (r(sp) 0.72-0.79). Dog owners
      were quite consistent in reporting living patterns, exercise and dog-training
      activities (r(sp) 0.65-0.94, kappa 0.43-0.88), except for number of walks per day
      (r(sp) 0.50). The repeatabilities also were excellent for the evaluation of
      health status (r(sp) 0.78-0.99, kappa 0.81-1.00). The questionnaire also was
      compared to a 7-day weighed record of total food intake and registration of
      exercise to give data on the validity. The questionnaire was given 62 (S.D. 19)
      days before the weighed registrations, and the overall response percentage was
      76% (58/76). Correlations for the frequency and amount of commercial feeds given
      were high (0.81-0.92), although correlations for specific table foods had a wider
      range (0.03-0.81). Correlations for total energy, protein, fat and carbohydrate
      intakes were between 0.80 and 0.85 in the total diet, and 0.79-0.85 in the
      commercial part of the diet. The correlations for frequency and amount of
      exercise ranged between 0.50 and 0.77. Corresponding correlations for training
      activities (such as hunting, tracking, and obedience) were 0.51-0.68.

PMID- 11448495
TI  - The effect of discontinuing the use of antimicrobial growth promoters on the
      productivity in the Danish broiler production.
AB  - On 15 February 1998, the Danish poultry industry voluntarily decided to
      discontinue the use of all antimicrobial growth promoters (AGPs). To investigate
      how the removal of AGPs influenced the broiler productivity in Denmark, data from
      6815 flocks collected from November 1995 to July 1999 by the Danish Poultry
      Council were analysed. The three flock parameters were: kilogram broilers
      produced per square meter (per rotation), feed-conversion ratio (total kilogram
      feed used per rotation/total kilogram live weight per rotation) and total percent
      dead broilers ((number of dead broilers during the rotation/number of broilers
      put in the house per rotation)x100). Data were analysed using a mixed model,
      allowing the correlation structures in the data to be taken into account. The
      analyses showed that kilogram broilers produced per square meter and percent dead
      broilers in total were not affected by the discontinued use of AGPs. However, the
      feed-conversion ratio increased marginally 0.016 kg/kg and has remained at this
      level throughout the rest of the study period.

PMID- 11448496
TI  - A Bayesian approach to estimating the performance of a bovine virus diarrhoea
      virus (BVDV) antibody ELISA bulk-tank milk test.
AB  - We investigated the operational performance (sensitivity and specificity) of a
      bovine virus diarrhoea virus (BVDV) antibody ELISA bulk-tank milk test for
      predicting the herd BVDV antibody status in young stock (as a relatively precise
      indicator of active BVDV infection). The study was based on results from the
      annual screenings under the Norwegian bovine virus diarrhoea (BVD) control and
      eradication program, lasting from 1993 to 1997. Empirical information from these
      annual screenings was the basis for prior assumptions about the true prevalence
      of young-stock-positive herds. Assumptions about prior distributions for
      sensitivity and specificity were based on the literature. Improved posterior test
      performance estimates were achieved applying a Bayesian approach using Gibbs
      sampling simulation. The simulations were run separately for each year, and
      yielded median values for sensitivity of 87% at the cut-off used in the BVD
      program. The posterior distributions were wide indicating much uncertainty in
      these estimates. The specificity estimates ranged from 79 to 92% and had narrower
      posterior estimates. The estimates differed by year. When running the same
      simulation procedures at a lower cut-off --after altering the sensitivity and
      specificity priors--the median sensitivity estimates increased to about 95%; the
      median specificity ranged from 71 to 83%. Due to low prevalence, the Bayesian
      method lacked power to assess the test sensitivity. A technically simpler
      descriptive graphing procedure (based on empirical information) provided equally
      useful insight into the bulk-tank milk test performance.

PMID- 11448497
TI  - Risk factors for Campylobacter spp. contamination in French broiler-chicken
      flocks at the end of the rearing period.
AB  - Our objectives were to identify risk factors for contamination of French broiler
      flocks by Campylobacter. We used 75 broiler farms in western France. A
      questionnaire was administered to the farmers and samples of fresh droppings were
      taken to assess the Campylobacter status of the broiler flocks. 42.7% of the
      flocks were positive for Campylobacter spp. The risk of contamination of the
      broiler flocks by Campylobacter was increased in summer/autumn, in houses with
      static air distribution, when two or more people took care of the flock, in
      poultry farms with three or more houses and when the drinking water for the
      chickens was acidified. The presence of litter-beetles in the change room also
      increased the risk of contamination. The administration of an antibiotic
      treatment following a disease decreased the risk of a flock being contaminated by
      Campylobacter.

PMID- 11448498
TI  - Simulating the effect of eliminating routine bacterial screening on the negative
      predictive value of the Ontario fish hatchery disease monitoring program.
AB  - We determined the impact of eliminating routine screening for Aeromonas
      salmonicida and Yersinia ruckeri on the efficacy of the Ontario Ministry of
      Natural Resources (OMNR) fish disease monitoring program, using Monte Carlo
      simulation. Because the main purpose of the program is to prevent transferring
      infected fish among OMNR hatcheries, or to wild fish populations through stocking
      waterways, the hatchery-level negative predictive value (HNPV) was used as an
      indicator of monitoring efficacy. The present program (which includes both
      routine screening of asymptomatic hatchery fish, and diagnostic testing of
      hatchery mortalities and clinically diseased fish) was confirmed to have a high
      median HNPV (0.999) for both study pathogens. Simulations suggested that the
      median probabilities that a hatchery would be pathogen-free if only diagnostic
      testing were continued (i.e. if no asymptomatic lots were screened), and all
      diseased lots tested negative for A. salmonicida and Y. ruckeri would be 0.994
      for both pathogens (with <5% probability that HNPV would be less than 0.953 and
      0.957, respectively) - indicating acceptable monitoring efficacy. However,
      limitations of the theoretical monitoring model must be considered.

PMID- 11448499
TI  - A retrospective analysis of the infectious bovine rhinotracheitis (bovine herpes
      virus-1) surveillance program in Norway using Monte Carlo simulation models.
AB  - Serological surveillance for antibodies against bovine herpes virus type I (BHV
      1) which causes infectious bovine rhinotracheitis and infectious pustular
      vulvovaginitis has been carried out since 1992 in Norway. Since 1993 (when a
      single infected herd was detected) all bulk-milk and pooled-serum samples have
      been negative for BHV-1 antibodies. This paper describes the use of Monte Carlo
      simulation models for the analysis and interpretation of the results of the
      surveillance and provides support for the contention that the Norwegian cattle
      population is not infected by BHV-1.

PMID- 11448500
TI  - The use of multilevel models to evaluate sources of variation in reproductive
      performance in dairy cattle in Reunion Island.
AB  - Sources of variation in measures of reproductive performance in dairy cattle were
      evaluated using data collected from 3207 lactations in 1570 cows in 50 herds from
      five geographic regions of Reunion Island (located off the east coast of
      Madagascar). Three continuously distributed reproductive parameters (intervals
      from calving-to-conception, calving-to-first-service and first-service-to
      conception) were considered, along with one Binomial outcome (first-service
      conception risk). Multilevel models which take into account the hierarchical
      nature of the data were used to fit all models. For the overall measure of
      calving-to-conception interval, 86% of the variation resided at the lactation
      level with only 7, 6 and 2% at the cow, herd and regional levels, respectively.
      The proportion of variance at the herd and cow levels were slightly higher for
      the calving-to-first-service interval (12 and 9%, respectively) - but for the
      other two parameters (first-service-conception risk and first-service-to
      conception interval), >90% of the variation resided at the lactation level. For
      the three continuous dependent variables, comparison of results between models
      based on log-transformed data and Box-Cox-transformed data suggested that minor
      departures from the assumption of normality did not have a substantial effect on
      the variance estimates. For the Binomial dependent variable, five different
      estimation procedures (penalised quasi-likelihood, Markov-Chain Monte Carlo,
      parametric and non-parametric bootstrap estimates and maximum-likelihood) yielded
      substantially different results for the estimate of the cow-level variance.

PMID- 11448501
TI  - Association between Chlamydia psittaci seropositivity and abortion in Italian
      dairy cows.
AB  - Although the seroprevalence of Chlamydia psittaci is widespread in Italian dairy
      herds, its role in inducing genital disorders has not been elucidated. We
      therefore set up a case-control study to compare seroprevalence to C. psittaci in
      an aborted-cow population and in a randomly selected control group in the
      province of Parma (the Po Valley of northern Italy). The true seroprevalence
      (45%) in aborted cows was significantly higher than that in the control group
      (24%) (adjusted odds ratio=2.53).

PMID- 11448502
TI  - Risk factors for intestinal pathogens in Danish finishing pig herds.
AB  - The objective of this investigation was to identify risk factors for infection
      with the intestinal bacteria: Lawsonia intracellularis, Brachyspira
      hyodysenteriae, Serpulina intermedia, Brachyspira innocens, Brachyspira
      pilosicoli and swine-pathogenic Escherichia coli (serogroups O138, O139, O141 and
      O149) in Danish finishing pig herds.A total of 79 herds was randomly selected and
      visited during 1998. From each herd, 20 faecal samples were collected from
      individual pigs weighing 30-50 kg. In total, 1580 faecal samples were collected
      and examined by polymerase chain reaction (L. intracellularis) or culture (all
      other agents). Information on feed and management procedures was collected by
      filling in questionnaires at the herd visits. The questionnaires included
      information on 29 dichotomous variables and three continuous variables. Variables
      with P<0.25 in a preliminary screening (chi2- or t-test) were selected for the
      statistical modelling. Our conclusions, based on the results of multifactorial
      logistic regression (cut-off: P=0.05), were the following: 1. Consistent batch
      production was associated with reduced prevalences of L. intracellularis and
      weakly -haemolytic spirochetes (S. intermedia, B. innocens, B. pilosicoli)
      (OR's=0.43 and 0.06, respectively). 2. Home-mixed (and/or non-pelleted) feed was
      associated with reduced prevalences of L. intracellularis and weakly -haemolytic
      spirochetes (OR's=0.6 and 0.4, respectively). 3. Providing straw to finishers was
      associated with a reduced prevalence of weakly -haemolytic spirochetes (OR=0.28
      0.32). 4. Not using antimicrobial growth promoters for piglets was associated
      with an increased prevalence of S. intermedia (OR=11.11). 5. Rare occurrence of
      post-weaning diarrhoea (as opposed to common) was associated with an increased
      prevalence of weakly -haemolytic spirochetes (OR=8.3-13.7).

PMID- 11448503
TI  - Group-level factors associated with chemotherapeutic treatment regimens in land
      based trout farms in Ontario, Canada.
AB  - The lowest level at which fish farmers ordinarily make management decisions is
      the individual holding unit. To identify factors associated with chemotherapeutic
      treatment initiation at the holding-unit level, we created a unit of measurement
      called the "farm-tank-lot" (FTL), which allowed the movements and mixing of
      groups of fish to be followed during an entire production cycle. Each FTL was
      comprised of fish with a common history housed in a specific holding unit. Our 21
      month prospective observational study (conducted on 14 land-based trout farms in
      Ontario, Canada) showed that the FTL was a biologically meaningful unit of
      concern and a feasible unit of measurement on land-based trout
      farms.Multivariable logistic and Poisson regressions revealed that fish size and
      growth rate both were associated negatively with the probability and frequency of
      treatment. FTLs that existed for longer periods of time were more likely to be
      treated and treated more often. There was a significant farm effect. Future field
      studies of disease in cultured fish should incorporate these factors into their
      design and analysis.

PMID- 11448504
TI  - Peri-parturient helminthosis in strains of small East African goats in Tanzania.
AB  - The effect of physiological status (e.g. pregnancy and lactation) on the
      susceptibility to gastrointestinal nematodes was studied in the Dodoma and Kigoma
      strains of small East African goats in Morogoro. Forty-six pregnant does (19
      Dodoma and 27 Kigoma strain) and 123 non-pregnant/dry (68 Dodoma and 55 Kigoma)
      from a controlled-breeding programme were used. Does were grazed on naturally
      contaminated pastures at Sokoine University of Agriculture for 8 months. Faecal
      samples and whole blood for determination of faecal egg counts (FEC), packed-cell
      volume (PCV) and blood eosinophils (EOS) from each animal were collected at
      monthly intervals from the mating period (through the gestation period) to 3
      months after kidding. From kidding to 3 months after kidding, lactating does had
      significantly higher FEC than non-lactating/dry does. From 1 month after kidding
      to 3 months after kidding, lactating does had significantly lower PCV than dry
      does. Blood eosinophils were higher in non-lactating/dry does than lactating does
      but only significant at 3 months after kidding. There were no significant
      differences in FEC, PCV and EOS between lactating Dodoma and lactating Kigoma
      does. We concluded that there was no difference in peri-parturient helminthosis
      between Dodoma and Kigoma strains and that blood eosinophilia decreased during
      peri-parturient helminthosis in both strains.

PMID- 11448507
TI  - Sleepiness: evaluating and quantifying methods.
AB  - The aim of this literature review is to analyze the methods mainly used for
      evaluating and quantifying the complex phenomenon of sleepiness. The most common
      distinction is between subjective measures or self-evaluations, performance
      decrement measures, measures for evaluating sleep propensity and measures of
      arousal decrease. Techniques mainly used in specialized literature will be
      briefly presented and commented upon, evaluating their sensitivity, advantages
      and limitations. We conclude that: (a) different measures inevitably are
      differently sensitive to sleepiness fluctuations; (b) the amount of prior sleep
      is strongly relevant in quantifying sleepiness levels; (c) subjective and
      behavioral measures show a higher level of vulnerability to external and
      motivational factors.

PMID- 11448508
TI  - A comparison of the different interpair intervals in the conditioning-testing P50
      paradigms.
AB  - The conditioning-testing P50 paradigm is used to demonstrate sensory gating of
      responsiveness to auditory stimuli. Sensory gating is measured in terms of a
      suppression of the second (test) P50 component in that paradigm. The time course
      of sensory gating can be determined by examining subjects' gating of
      responsiveness to stimuli repeated at various interpair intervals. In the present
      study auditory evoked potentials were recorded using a paired click, conditioning
      testing P50 paradigm in 11 normal subjects with no family history of any
      psychotic disorder. Recordings were made at conditioning-testing intervals of 250
      ms, 500 ms, 750 ms and 1000 ms. Whereas the grand averages of the P50
      conditioning-testing response for the 250- and 500-ms intervals were 3.07% and
      37.2%, respectively, indicating almost complete suppression, the grand averages
      of the ratios for the 750- and 1000-ms intervals were 114.35% and 92.92%,
      respectively, indicating little or no suppression. There was significant
      correlation in the C-T ratios with the increasing intervals. Our results suggest
      that the mechanism(s) responsible for sensory gating is activated mostly during
      the 500 ms after stimulus presentation. Other gating mechanism(s) functioning at
      longer intervals appear to be uncertain.

PMID- 11448509
TI  - Dynamic behavior of the auditory N100 elicited by a baby's cry.
AB  - We compared auditory N100 responses in female adults to two non-attended human
      sound stimuli. An infant's cry represented an unfamiliar, emotionally colored
      sound and the Finnish word "hei" (meaning "hi") a familiar and emotionally
      neutral sound. Both sounds elicited clear N100 responses over auditory areas in
      both hemispheres. However, the dynamic behavior of the N100 response following
      the first few repetitions of the sounds was significantly different. We observed
      faster habituation and longer response latencies, particularly over the
      ipsilateral hemisphere, during the first and second repetitions of the cry
      stimulus. This pattern may reflect an altered arousal level and slower, bilateral
      processing during the unfamiliar emotionally loaded cry as compared to the
      emotionally neutral word "hei" .

PMID- 11448510
TI  - Intracellular dynamics of steroid hormone receptor.
AB  - Steroid hormones substantially influence brain development, reproduction sexual
      differentiation and emotion. These effects are mediated by steroid hormone
      receptors and cofactors, which directly regulate gene expression. Deciphering how
      and where these transcriptional activators occur in a cell provides the
      groundwork for elucidating the influence of these small hydrophobic signal
      molecules on various brain functions. This paper describes some of the recent
      investigations into the subcellular localization of steroid hormone receptors and
      cofactors using GFPs and other immunocytochemical methods.

PMID- 11448511
TI  - Endogenous cannabinoid as a retrograde messenger from depolarized postsynaptic
      neurons to presynaptic terminals.
AB  - Cannabinoid receptors are the molecular targets for the active component Delta(9)
      tetrahydrocannabinol of marijuana and hashish, and constitute a major family of G
      protein-coupled seven-transmembrane-domain receptors. They consist of type 1
      (CB1) and type 2 (CB2) receptors of which the CB1 is rich in various regions of
      the CNS. Accumulated evidence suggests that endogenous cannabinoids function as
      diffusible and short-lived intercellular messengers that modulate synaptic
      transmission. Recent studies have provided strong experimental evidence that
      endogenous cannabinoids mediate signals retrogradely from depolarized
      postsynaptic neurons to presynaptic terminals to suppress subsequent
      neurotransmitter release, driving the synapse into an altered state. In
      hippocampal neurons, depolarization of postsynaptic neurons and resultant
      elevation of [Ca(2+)](i) lead to transient suppression of inhibitory transmitter
      release (depolarization-induced suppression of inhibition, DSI). In cerebellar
      Purkinje cells, on the other hand, depolarization-induced elevation of
      [Ca(2+)](i) causes transient suppression of excitatory transmitter release
      (depolarization-induced suppression of excitation, DSE). DSI and DSE appear to
      share the same properties and may be a general and important mechanism by which
      the postsynaptic neuronal activity can influence the amount of transmitter
      release.

PMID- 11448512
TI  - Modulation of inward rectifier potassium channel by toosendanin, a presynaptic
      blocker.
AB  - The effect of toosendanin, a presynaptic blocker, on the inward rectifier
      potassium channel (K(Kir)) of hippocampal CA1 pyramidal neurons of rats was
      studied by the single-channel patch-clamp technique. The results showed that
      toosendanin had an inhibitory effect on K(Kir) in an excised inside-out patch of
      the neuron under a symmetrical 150 mM K(+) condition. By decreasing the slower
      open time constant and increasing the slower close time constant, toosendanin
      (1x10(-6)-1x10(-4) g/ml) significantly reduced the open probability of the
      channel in a concentration-dependent manner. Meanwhile, a dose-dependent
      reduction in unitary conductance of the channel was also detected after
      toosendanin application. These data offer an explanation for toosendanin-induced
      facilitation of neurotransmitter release and antibotulismic effect of the drug.

PMID- 11448513
TI  - Blocking AMPA receptor desensitization prolongs spontaneous EPSC decay times and
      depolarizes H1 horizontal cells in carp retinal slices.
AB  - Desensitization of H1 horizontal cell (H1 HC) glutamate receptors was
      investigated in carp retinal slices using cyclothiazide (CTZ), an inhibitor of
      AMPA receptor desensitization. 100 microM CTZ depolarized H1 HCs and increased
      the amplitude of light responses, without any prominent changes in their
      kinetics. Spontaneous EPSCs (sEPSCs) in H1 HCs were observed in the presence of
      2.5 mM heptanol, an uncoupling agent of gap junctions. 20 microM GYKI52466 (an
      AMPA receptor antagonist) blocked the sEPSCs, consistent with the sEPSCs being
      mediated by AMPA receptors. 100 microM cobalt suppressed the frequency of sEPSCs
      without changing their mean peak amplitude, suggesting that calcium-dependent
      transmitter release from cones was not affected by heptanol. CTZ increased the
      total inward charge transferred per sEPSC by increasing the sEPSC decay time
      constant twofold, without any significant change in their frequency and mean peak
      amplitude. This suggests that the depolarizing effect of CTZ on H1 HCs was due to
      blocking desensitization of AMPA receptors, increasing the inward current induced
      by glutamate released from cone synaptic terminals. The desensitization of
      glutamate receptors may function to extend the dynamic range of H1 HC light
      responses.

PMID- 11448514
TI  - Induction by carrageenan inflammation of prepronociceptin mRNA in VR1
      immunoreactive neurons in rat dorsal root ganglia.
AB  - Nociceptin (orphanin FQ) may act on primary afferents and be involved in the
      regulation of nociceptive processing. We have shown, using reverse transcription
      polymerase chain reaction (RT-PCR), that carrageenan-produced peripheral
      inflammation induces the expression of prepronociceptin (PPN) mRNA in the dorsal
      root ganglia (DRG). The present experiments were conducted to determine the
      localization of PPN mRNA in primary sensory neurons after peripheral
      inflammation, using in situ hybridization. An intraplantar injection of
      carrageenan induced the expression of PPN mRNA in small and medium sized neurons
      in the DRG; the effect peaked 0.5 h after carrageenan and subsided by 6 h. All
      neurons positive for PPN mRNA were positive for vanilloid receptor subtype 1
      (VR1)-like immunoreactivity and some VR1-immunoreactive neurons were negative for
      PPN mRNA. The results suggest that peripheral inflammation induces the production
      of nociceptin in a sub-population of VR1-positive primary sensory neurons and
      support the idea that nociceptin produced there is involved in the regulation of
      nociceptive processing.

PMID- 11448515
TI  - Response of amoeboid and differentiating ramified microglia to glucocorticoids in
      postnatal rats: a lectin histochemical and ultrastructural study.
AB  - After glucocorticoid injection(s), the number of amoeboid microglial cells (AMC)
      in the corpus callosum labelled by lectin was markedly reduced when compared with
      the corresponding control rats. In rats killed at the age of 7 days, all the
      labeled cells differentiated to become ramified microglia. Ultrastructurally, the
      AMC in glucocorticoid-injected rats were extremely vacuolated and showed
      increased lipid droplets. Furthermore, the cells displayed varied lectin
      labelling patterns especially at both the trans saccules of the Golgi apparatus
      and lysosomes. In differentiating ramified microglia, massive cellular debris and
      lectin-stained vesicles or vacuoles were observed; some of the latter appeared to
      fuse with the plasma membrane. The most striking feature after glucocorticoid
      (GCC) treatment was the complete diminution of lectin labelling at the Golgi
      saccules in some differentiating ramified microglia. The present results have
      demonstrated different effects of glucocorticoids on AMC and differentiating
      ramified microglia. The differential response of AMC and differentiating ramified
      microglia to the immunosuppressive drugs may be attributed to the fact that these
      cells in the postnatal brains subserve different functions or that they are at
      different differentiation stages. In other words, the sensitivity of microglial
      cells to the immunosuppressive drugs is dependent upon the stage of cell
      maturation/differentiation.

PMID- 11448516
TI  - Hypoxia induces an excitotoxic-type of dark cell degeneration in cerebellar
      Purkinje neurons.
AB  - In the rat cerebellar slice preparation, exposure to hypoxia elicited by a 30 min
      exposure to artificial cerebrospinal fluid continuously gassed with 95% N(2): 5%
      CO(2) induced a characteristic type of toxicity of Purkinje cells (PCs)
      resembling excitotoxic-mediated dark cell degeneration (DCD). Morphologically,
      PCs exhibited marked rounded appearance with cytoplasmic darkening, nuclear
      condensation and cytoplasmic vacuoles. Using gel electrophoresis, genomic DNA
      obtained from the cerebellar slice exhibited fragmentation. However, PCs failed
      to exhibit apoptotic bodies or evidence of phagocytosis, spherical- or crescent
      shaped chromatin aggregations or TUNEL-positive staining. Ultrastructural
      analyses of granule cells revealed the presence of apoptotic bodies and discrete
      spherical collection of chromatin clumping as well as phagocytosis suggesting
      that the oligonucleosomal-sized DNA fragments primarily were derived from granule
      cells. PC-elicited toxicity was attenuated significantly in the presence of the
      competitive AMPA and NMDA antagonists CNQX and APV, respectively. The present
      study extends the involvement of excitotoxic processes in mediating hypoxic
      induced toxicity of PCs in postnatal rats and suggests, in contrast to DCD
      elicited by direct application of excitotoxic agents, that DCD associated with
      acute hypoxic insults in PCs does not resemble classical apoptosis.

PMID- 11448517
TI  - Modulation of absence seizures by branched-chain amino acids: correlation with
      brain amino acid concentrations.
AB  - The occurrence of absence seizures might be due to a disturbance of the balance
      between excitatory and inhibitory neurotransmissions in the thalamo-cortical
      loop. In this study, we explored the consequences of buffering the glutamate
      content of brain cells on the occurrence and duration of seizures in Genetic
      Absence Epilepsy Rats from Strasbourg (GAERS), a genetic model of generalized non
      convulsive epilepsy. Branched-chain amino acids (BCAAs) and alpha-ketoisocaproate
      (alpha-KIC), the ketoacid of leucine were repeatedly shown to have a critical
      role in brain glutamate metabolism. Thus, GAERS were injected by intraperitoneal
      (i.p.) or intracerebroventricular (i.c.v.) route with these compounds, then the
      effects on seizures were evaluated on the electroencephalographic recording. We
      also measured the concentration of amino acids in thalamus and cortex after an
      i.p. injection of leucine or alpha-KIC. Intracerebroventricular injections of
      leucine or alpha-KIC did not influence the occurrence of seizures, possibly
      because the substances reached only the cortex. BCAAs and alpha-KIC, injected
      intraperitoneally, increased the number of seizures whereas they had only a
      slight effect on their duration. Leucine and alpha-KIC decreased the
      concentration of glutamate in thalamus and cortex without affecting GABA
      concentrations. Thus, BCAAs and alpha-KIC, by decreasing the effects of
      glutamatergic neurotransmission could facilitate those of GABAergic
      neurotransmission, which is known to increase the occurrence of seizures in
      GAERS.

PMID- 11448518
TI  - 5-Hydroxytryptamine facilitates spatiotemporal propagation of optical signals in
      the hippocampal-septal pathway.
AB  - The role of 5-hydroxytryptamine (5-HT) on the propagation of neuronal excitation
      in the hippocampal-septal pathway was examined in a brain slice by optical and
      electrophysiological recording techniques. After electrical stimulation of the
      fimbrial pathway, optical signals first occurred at the caudal region of lateral
      septal nucleus (LSN), then propagated toward the rostral region of LSN. All of
      the evoked optical signals were blocked by tetrodotoxin (TTX). The optical signal
      that propagated to the LSN was blocked by either the removal of external Ca(2+)
      or bath-application of 6-cyano-7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX). Bath
      application of 5-HT (1-50 microM) to the LSN for 10 min produced an increase in
      the propagation area of the optical signal and prolonged the falling phase of the
      optical signal. Bicuculline blocked the 5-HT-induced facilitation of the optical
      signal. 8-Hydroxy-di-n-propylamino tetralin (8-OH-DPAT), a selective 5-HT(1A)
      agonist, mimicked the facilitation of 5-HT. 1-(2-Methoxyphenyl)-4-(4
      phthalimidobutyl)piperazine (NAN-190), a 5-HT(1A) antagonist, blocked the
      facilitation induced by 5-HT. 5-HT enhanced the amplitude of the field potential
      in septal slices, where the optical signals had been enhanced. These results
      indicate that 5-HT increases the efficacy of excitatory synaptic transmission in
      the hippocampal-septal circuit via 5-HT(1A) receptors of LSN neurons.

PMID- 11448519
TI  - Hypothyroidism in the developing rat brain is associated with marked oxidative
      stress and aberrant intraneuronal accumulation of neurofilaments.
AB  - The effects of hypothyroidism on parameters of oxidative stress and on
      intraneuronal distribution of neurofilaments have been investigated in the
      developing rat brain. Progressive hypothyroidism during the first 4 weeks of
      postnatal development led to an increase in superoxide dismutase and catalase
      activity, decline in the level of glutathione and mitochondrial cytochrome c
      oxidase activity and increase in the level of .OH radical along with enhanced
      protein carbonylation and lipid peroxidation. Immunocytochemical staining of
      cryostat sections of normal and hypothyroid cerebella from 25 day postnatal rats
      with anti neurofilament (NF) light chain (L) antibody showed aberrant
      accumulation of neurofilaments in the perikaryon of the hypothyroid Purkinje
      neurons in contrast to relatively uniform distribution in the controls. The
      morphological and biochemical alterations in the neurons of the developing
      hypothyroid brain are comparable to those seen in several neurodegenerative
      diseases.

PMID- 11448520
TI  - Quantitative and temporal relationship between local cerebral blood flow and
      neuronal activation induced by somatosensory stimulation in rats.
AB  - In many studies on functional neuroimaging, change in local cerebral blood flow
      induced by sensory stimulation (evoked LCBF) is used as a marker for change in
      cortical neuronal activity, although a full description of the relationship
      between the evoked LCBF and neuronal activity has not been given. The purpose of
      this study was to estimate the close relationship between the evoked LCBF and
      neuronal activity. We measured the field potential using an electrode inserted
      into the cortex and the evoked LCBF using Laser-Doppler flowmetry in alpha
      chloralose-anesthetized rats during somatosensory stimulation. Activation of the
      cortex was carried out by electrical stimulation of the hind paw with 1.5 mA
      pulses (0.1 ms) applied at the frequencies of 0.2,1,5 and 10 Hz for a 5 s
      duration, and at the frequencies of 1 and 5 Hz for 2,5 and 15 s durations. The
      response magnitude of the evoked LCBF reached the maximum at 5 Hz. During the 5 s
      stimulation, the pattern of change in the response magnitude of evoked LCBF to
      various frequencies reflected the integrated amplitude of field potentials.
      During the 15 s stimulation, the evoked LCBF at 5 Hz exhibited an initial peak
      followed by a plateau phase, although there was no initial peak at 1 Hz. These
      changes in evoked LCBF during the 15 s stimulation reflected change in field
      potentials, but they were delayed during the temporal change in field potentials.
      These results suggest that the response of evoked LCBF reflects the integrated
      neuronal activity during the stimulation period, and it is modulated by a
      temporal slow function.

PMID- 11448521
TI  - Kinetic analysis of enzyme systems with suicide substrate in the presence of a
      reversible, uncompetitive inhibitor.
AB  - We present a general kinetic analysis of enzyme catalyzed reactions evolving
      according to a Michaelis-Menten mechanism, in which an uncompetitive, reversible
      inhibitor acts. Simultaneously, enzyme inactivation is induced by an unstable
      suicide substrate, i.e. it is a Michaelis-Menten mechanism with double
      inhibition: one originating from the substrate and another originating from the
      reversible inhibitor. Rapid equilibrium of the reversible reaction steps involved
      is assumed and the time course equations for the reaction product have been
      derived under the assumption of limiting enzyme. The goodness of the analytical
      solutions has been tested by comparison with simulated curves obtained by
      numerical integration. A kinetic data analysis to determine the corresponding
      kinetic parameters from the time progress curve of the product is suggested.

PMID- 11448522
TI  - Evolving hardware as model of enzyme evolution.
AB  - Organism growth and survival is based on thousands of enzymes organized in
      networks. The motivation to understand how a large number of enzymes evolved so
      fast inside cells may be relevant to explaining the origin and maintenance of
      life on Earth. This paper presents electronic circuits called 'electronic
      enzymes' that model the catalytic function performed by biological enzymes.
      Electronic enzymes are the hardware realization of enzymes defined as molecular
      automata with a finite number of internal conformational states and a set of
      Boolean operators modelling the active groups of the active site. One of the main
      features of electronic enzymes is the possibility of evolution finding the proper
      active site by means of a genetic algorithm yielding a metabolic ring or k-cycle
      that bears a resemblance to Krebs (k=7) or Calvin (k=4) cycles present in
      organisms. The simulations are consistent with those results obtained in vitro
      evolving enzymes based on polymerase chain reaction (PCR) as well as with the
      general view that suggests the main role of recombination during enzyme
      evolution. The proposed methodology shows how molecular automata with evolvable
      features that model enzymes or other processing molecules provide an experimental
      framework for simulation of the principles governing metabolic pathways evolution
      and self-organization.

PMID- 11448523
TI  - Respiratory sinus arrhythmia from two coupled pacemakers.
AB  - We reproduce global features of respiratory sinus arrhythmia (RSA), a prominent
      source of heart rate variability, from two signals coupled in alternate fashion
      so dominance periodically switches back and forth between them. We consider two
      different possibilities for this coupling and illustrate our method with
      numerical simulations that we contrast with the corresponding results from real
      data. We interpret our findings within the context of the two-pacemaker model of
      the heartbeat, an alternative to the single-pacemaker mechanism of pulse
      generation in the orthodox conduction model.

PMID- 11448524
TI  - Information obtained in cladistic analysis.
AB  - The application of elementary equations from information theory to the elements
      involved in cladistic analysis is formalized mathematically. An equation is
      derived that quantifies the amount of information obtained by constructing a
      cladogram from a cladistic data matrix. Given particular conditions, the amount
      of information obtained increases monotonically with increases of the number of
      taxa involved and, so, may be used directly as a comparative measure of species
      richness for sister groups; in general, however, the amount of information
      obtained is related to the distribution of character states on the cladogram(s)
      deduced. An example is presented in which clades representing 11 phyla in the
      animal kingdom are compared in terms of information yielded. The amount of
      information obtained is consistent for different numbers of taxa and characters
      used in classifications. Speculative evolutionary explanations are presented for
      differences of information yielded among the phyla analyzed.

PMID- 11448525
TI  - Studies into abstract properties of individuals. VI. The degree of emergence in
      individuals, populations, species and a three species lineage.
AB  - Emergent properties derived from the integration among descriptive variables were
      explored in three related grass species, Achnatherum lemmonii, Achnatherum
      hendersonii and Achnatherum wallowaensis. Different levels of organization were
      compared: individuals, populations, species, species-pairs and all three species
      combined. Emergence was seen at all levels with populations having the lowest
      degree followed by individuals, species and combinations of species. Because
      there were no variables unique to any level analyzed, emergence is more than the
      appearance of new structures. As the degree of emergence increases there is also
      an increase in variation in integration, the result of new growth rates. Time may
      explain the different degrees of emergence at the different levels. The trend
      populations-species-combination of species is easily related to time; the first
      are younger than the last. An individual develops over a greater period of time
      than a population. The greater time of existence of a species may account for a
      greater degree of emergence than an individual. In an individual the local time
      expressed during ontogeny establishes boundary conditions for an individual. As
      that local time becomes incorporated into global, or phylogenetic, time, the
      boundary conditions for taxa and lineages is established.

PMID- 11448526
TI  - Towards a cognitive niche: divergent foraging strategies resulting from limited
      cognitive ability of foraging herbivores in a spatially complex environment.
AB  - A model was developed to explain one mechanism whereby differential optimal
      foraging strategies can occur between species as a result of selection for
      competition avoidance. This is the primary requirement for niche differentiation
      to evolve without a difference in the underlying foraging ability or morphology.
      The model used an individual-based patch choice mechanism, whereby herbivores
      move from patch to patch seeking food with the highest nutrient intake
      characteristics. The choice of patch was governed by a parameter, mu, which
      determined to what extent information in the landscape at different distances
      from the herbivore was used by it to make foraging decisions. A genetic algorithm
      was used to optimise the value, mu, in a complex landscape. The value of mu
      quickly converged to a single value with stabilising selection occurring when
      there was only a single species foraging. When there was a competing species with
      a fixed value of mu, the value of mu evolved to be above or below the mean for
      the single species mean depending on whether the value of mu for the competitor
      was below, or above the single-species mean, respectively. This was indicative of
      niche segregation. However mu tended to vary unstably over time when allowed to
      vary simultaneously in both species, although there was evidence for interaction
      between the two values. These results indicate that there can be a competitive
      advantage in choosing a cognitive strategy that is complementary to that used by
      other species.

PMID- 11448527
TI  - Origins of life: a route to nanotechnology.
AB  - The origins of life and nanotechnology are two seemingly disparate areas of
      scientific investigation. However, the fundamental questions of life's beginnings
      and the applied construction of a Drexlerian nanotechnology both share a similar
      problem; how did and how can self-reproducing molecular machines originate? Here
      we draw attention to the coincidence between nanotechnology and origins research
      with particular attention paid to the spontaneous adsorption and scanning
      tunneling microscopy investigation of purine and pyrimidine bases self-organized
      into monolayers, adsorbed to the surfaces of crystalline solids. These molecules
      which encode biological information in nucleic acids, can form supramolecular
      architectures exhibiting enantiomorphism with the complexity to store and encode
      putative protobiological information. We conclude that the application of
      nanotechnology to the investigation of life's origins, and vice versa, could
      provide a viable route to an evolution-driven synthetic life.

PMID- 11448528
TI  - Role of serine/threonine protein phosphatase 2A in cancer.
AB  - The serine/threonine protein phosphatase 2A (PP2A) appears to be critically
      involved in cellular growth control and potentially in the development of cancer.
      A few studies indicated that this enzyme might actually exert tumor suppressive
      function. However, other findings demonstrated the requirement for PP2A in cell
      growth and survival, which is not a characteristic of a typical tumor suppressor.
      This apparent discrepancy might be due to the fact that PP2A is a multitask
      enzyme system, rather than a single enzyme. Its individual subunits are encoded
      by a heterogeneous group of genes which give rise to a multitude of different
      PP2A holoenzyme complexes. Thus, the puzzling observation that PP2A exerts
      inhibitory, as well as stimulatory, effects on cell growth could be due to the
      activity of different PP2A complexes with distinct subcellular location and
      divers substrate specificity. At the same time, this abundance of PP2A components
      provides a large target for mutations that might derail proper enzyme function
      and could contribute to the process of tumorigenesis. So far, however, it has not
      been unequivocally established whether such mutations, examples of which have
      indeed been found in human cancer cells, result in the activation of an oncogenic
      function or rather in the inactivation of the presumed tumor suppressive role of
      PP2A. Therefore, the general opinion of PP2A as being a tumor suppressor needs to
      be viewed with caution.

PMID- 11448529
TI  - Inhibitory effects of anthraquinones and bianthraquinones on Epstein-Barr virus
      activation.
AB  - Short-term in vitro assays for anti-tumor promoters were carried out for several
      anthraquinones and bianthraquinones, which were isolated from Cassia siamea and
      derived from cascaroside A. Anthraquinone monomers showed higher anti-tumor
      promoting activity than that of bianthraquinones.

PMID- 11448530
TI  - Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese
      women with cervical intraepithelial neoplasia/cervical cancer in relation to
      their oncogenic potential.
AB  - The variation of the E6 region of human papillomavirus type 16 (HPV16) is
      associated with a high risk for cervical carcinogenesis. To see whether the same
      is the case with HPV33, 52 and 58, known to have high homology with HPV16, we
      analyzed the E6 sequence variation of these HPVs in 107 Japanese women with
      cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC): 20
      HPV33-positive, 46 HPV52-positive and 41 HPV58-positive cases. HPV33 variants
      were more frequently observed in CINs I/II than in CIN III/ICCs (71% (5/7) versus
      15% (2/13), P=0.02). In HPV52-positive cases, a single E6 variant was detected in
      98% of the cases, whereas the prototype accounted for 98% of HPV58-positive
      cases. In summary, the distribution of E6 variants is different among HPV types
      tested, suggesting a link between E6 variation and oncogenic potential being type
      specific.

PMID- 11448531
TI  - Application of standardized mistletoe extracts augment immune response and down
      regulates metastatic organ colonization in murine models.
AB  - The immunomodulatory and antimetastatic activity of standardized aqueous
      mistletoe extracts from plants grown on fir trees (ME-A) and pine trees (ME-P)
      were evaluated in BALB/c-mice. Regular subcutaneous (s.c.) and intraperitoneal
      (i.p.) applications (three times per week for 14 consecutive days; 5 and 50
      microg per injection and mouse) upregulated thymus weight and peripheral blood
      leukocyte counts in tumor bearing mice. To check the influence of ME-A and ME-P
      treatment on growth of experimental metastases, RAW 117 H 10 lymphosarcoma cells
      and L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish
      liver and lung colonization. ME-A and ME-P were regularly administered starting
      24 h after tumor cell challenge. Organ colonization was investigated on day 14
      after tumor cell inoculation and demonstrated statistically significant (P<0.05)
      reductions of experimental liver and lung metastases for ME-A and ME-P treated
      mice.

PMID- 11448532
TI  - Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia
      cells.
AB  - Carnosol, a phenolic compound extracted from the herb rosemary has been reported
      to have anti-cancer activity. We investigated whether carnosol was cytotoxic
      against several pro-B and pre-B acute lymphoblastic leukemia (ALL) lines. In all
      ALL lines tested, carnosol induced apoptotic cell death distinguished by loss of
      nuclear DNA, externalization of cell membrane phosphatidylserine, and
      depolarization of mitochondrial membranes. Flow cytometric measurement of Bcl-2
      protein levels revealed that carnosol induced a 34-53% decrease in Bcl-2 in the
      cell population exhibiting a viable phenotype prior to detectable apoptotic
      changes in morphology. These results suggest that carnosol may be useful as a
      novel chemotherapeutic agent against B-lineage leukemias, and possibly other
      types of cancers that express high levels of the protective protein, Bcl-2.

PMID- 11448533
TI  - Inhibition of green tea catechins against the growth of cancerous human colon and
      hepatic epithelial cells.
AB  - The ability of (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)
      epigallocatechin gallate (EGCG) to inhibit the growth of HCT 116 colorectal and
      Hep G2 hepatocellular carcinoma cells was examined by MTT and clonogenic assays
      (CA). The respective catechins inhibited the growth of HCT 116 more strongly than
      Hep G2. In MTT assay, IC(50) values of EGC and EGCG against HCT 116 grew smaller
      on prolongation of the exposure times of the cells to the catechins. In CA,
      however, these two catechins had IC(50) values ranging between 7.6+/-0.4 and
      11.2+/-0.5 microM against the same cells regardless of the exposure times. EC
      showed much weaker growth inhibitions relative to the two aforementioned
      catechins.

PMID- 11448534
TI  - Comparative study for histology, proliferative activity, glycoproteins, and p53
      protein between old and recent colorectal adenomas in Japan.
AB  - The incidence of colorectal carcinoma is increasing in Japan. Malignant
      transformation in colorectal neoplasia is usually considered to be owing to
      adenoma-carcinoma sequence. Elucidation of the recent alteration in the
      biological properties of colorectal adenoma is sure to be useful to understand
      the recent increase of the colorectal carcinoma in Japan. We compared the
      histopathological feature, mitotic index, proliferative activity (Ki-67 labeling
      index), expression of glycoproteins such as MUC2 mucin, sialyl Lewis A (SLe(a))
      and sialyl dimeric Lewis X (SLe(x)), and p53 protein overexpression, between 108
      adenomas in the old period (Group A, from 1969 to 1985) and 140 adenomas in the
      recent period (Group B, from 1995 to 1998). The histological dysplasia, mitotic
      index and Ki-67 labeling index of the adenomas were significantly higher in Group
      B than in Group A. In contrast, the expression of MUC2 mucin, which is considered
      to be a differentiation factor of intestinal mucosal epithelium, was
      significantly reduced in Group B than in Group A. The SLe(a) and SLe(x)
      expressions showed no significant difference between them. The p53 expression
      showed no significant difference between them, except for the moderate dysplasia.
      These findings indicate that recent colorectal adenomas show more advanced
      degrees of histological dysplasia, more rapid growth, and reduced differentiation
      than colorectal adenomas, which developed at earlier times, and may be related
      with the recent high incidence of colorectal carcinoma in Japan.

PMID- 11448535
TI  - hOGG1 exon7 polymorphism and gastric cancer in case-control studies of Japanese
      Brazilians and non-Japanese Brazilians.
AB  - Polymorphism of hOGG1 may be capable of serving as a genetic marker for
      individual susceptibility to various cancers because of its role in the repair of
      oxyradical DNA damage. We examined the distribution of the hOGG1 Ser326Cys
      polymorphism and its presumed correlation with gastric cancer risk in two case
      control studies of different ethnic groups in Sao Paulo, Brazil. Potentially
      eligible Japanese (JB) and non-Japanese Brazilian (NJB) case subjects were
      defined as patients with newly diagnosed malignant neoplasms of the stomach in 13
      hospitals in Sao Paulo. Ninety-six JBs and 236 NJBs were adopted as subjects. Two
      controls were matched for each JB case, and one control for each NJB case. The
      subjects were interviewed using a questionnaire and their blood samples were
      collected. A significant difference in the distribution of this polymorphism
      between the two ethnic groups was observed (chi(2)=58.3, P<0.01). The mutant type
      (Ser/Cys or Cys/Cys) was predominant (approximately 65%) in the JBs, but was only
      present in approximately 40% of the NJBs. Logistic regression analysis showed no
      significant increased risk for either the Ser/Cys or Cys/Cys type in either
      group. The odds ratios of the Cys allele for gastric cancer were 1.01 (95%
      confidence interval (CI): 0.52-1.93) in the JBs and 0.85 (95% CI: 0.57-1.26) in
      the NJBs. In the NJBs, a significant increased risk of smoking was shown only in
      the Ser/Ser type, and no increased risk was shown in the genotypes with the Cys
      allele. However, no statistically significant interactions were observed with
      smoking or other possible confounding factors. No statistically significant
      difference in the distribution of the polymorphism was observed between the
      intestinal type and diffuse type of gastric cancer in either the JBs or the NJBs.
      The ethnic difference in hOGG1 Ser326Cys polymorphism was much greater than the
      case-control difference, and this polymorphism is unlikely to be associated with
      gastric cancer.

PMID- 11448536
TI  - The p53 codon 249 mutant--derived from human functional adrenal tumors--can
      modify the cell shape of normal adrenocortical transfected cells.
AB  - Our previous study has indicated that p53 gene mutation occurred in 73% of human
      functional adrenal tumors, and the mutation hot spots were focused on codons 100,
      102 (exon 4), and 249 (exon 7). Furthermore, a transcriptional activity study
      revealed that the mutant p53 protein derived from human functional adrenal tumors
      lost 90% transcriptional activity and the ability to bind with the p53 sequence.
      In order to investigate the influence of the mutant protein extracted from
      adrenocortical tumors on normal adrenal cells, we first cloned p53 cDNA from the
      human primary aldosteronism and constituted it with isopropyl thiogalactoside
      (IPTG) inducible expression vector as recombinant plasmid. The recombinant
      plasmid was then transfected to normal bovine adrenocortical cells through
      electroporation. The results showed that the p53 protein mutations at codons 100
      and 102 could neither affect the cell morphology nor enable cell growth on the
      soft agar. In addition, no significant difference was found in cortisol level
      between the p53 transfected and the control cells. On the other hand, cell
      morphological changes and cell proliferation rate increase were observed when we
      used IPTG to induce the expression of the p53 protein, which mutated at codon
      249, in adrenocortical cells. The cell morphology changes included less flattened
      and decreased elongation when compared to non-transfected cells. However, the
      cortisol level in transfected cells was not affected by the p53 mutants. Taken
      together, we concluded that the mutant p53 protein indeed participates in adrenal
      carcinogenesis; however, it has no influence on hormone production and secretion.

PMID- 11448537
TI  - Methylation status in the promoter region of the human PGP9.5 gene in cancer and
      normal tissues.
AB  - PGP 9.5 is a neurospecific peptide that functions to remove ubiquitin from
      ubiquitinated cellular proteins, thereby preventing them from targeted
      degradation by the proteasome-dependent pathway or regulating their localization,
      activity or structure. Using the serial analysis of gene expression method
      (SAGE), we initially found that the PGP9.5 transcript and protein was highly
      expressed in more than 50% of primary lung cancers and nearly all lung cancer
      cell lines but was not detectable in the normal lung. This increased expression
      could be the result of transcriptional regulation accompanied by methylation
      changes at the CpG island of the promoter region. We studied the methylation
      status of the cytosines at the promoter region of human PGP9.5 using sodium
      bisulfite genomic sequencing in normal and neoplastic cells. Although no
      methylation of PGP9.5 promoter was observed in the normal lung, normal cervical
      tissue, and lung cancer cell lines, this region was densely methylated in the
      HeLa cell line. Exposure to HeLa cells to the demethylating agent, 5-aza-2'
      deoxycytidine, led to re-expression of PGP9.5. This data suggested that while
      other mechanisms may be involved in the frequent overexpression of PGP9.5 gene in
      lung tumors and lung cancer cell lines, promoter methylation may play a role in
      the transcriptional suppression of PGP9.5 gene expression in the cervical tissue
      derived HeLa cell line.

PMID- 11448538
TI  - Effect of serum depletion on centrosome overduplication and death of human
      pancreatic cancer cells after exposure to radiation.
AB  - The tumor microenvironment is one of the key factors affecting the cellular
      response to radiation; however, the influence of serum concentration on tumor
      radiosensitivity remains poorly understood. We recently discovered that gamma
      irradiation of tumor cells causes centrosome overduplication, which may lead to
      lethal nuclear fragmentation through the establishment of multipolar mitotic
      spindles. In the present study, we investigated the effect of serum depletion on
      radiation-induced cell death in relation to the centrosome dynamics in human
      pancreatic cancer cells. Exposure of Capan-1 cells to gamma-irradiation resulted
      in a time-dependent increase in cells containing multiple centrosomes in
      association with the appearance of mitotic cell death. Treatment of irradiated
      cells with serum depletion drastically accelerated centrosome overduplication and
      the formation of multipolar spindles, resulting in increased nuclear
      fragmentation and cell death. Cell cycle analysis of irradiated cultures revealed
      that the reduced serum level increased the population of cells arrested in the
      G2/M phase, which might be responsible for the abnormal centrosome accumulation.
      These findings suggest that serum concentration can influence radiation-induced
      cell killing through modulating cell cycle progression and possibly centrosome
      overduplication.

PMID- 11448539
TI  - Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA
      expression in human pancreatic cancers by real-time polymerase chain reaction.
AB  - Recent studies have disclosed the presence of a second estrogen receptor (ER; ER
      beta) in addition to a classical ER-alpha. ER-beta mRNA expression has yet to be
      studied in pancreatic cancers. Thus, we studied the expression of ER-alpha and ER
      beta mRNA in pancreatic cancers (n=29) by real-time quantitative reverse
      transcriptase-polymerase chain reaction, and compared the expression levels in
      pancreatic cancers with those in breast cancers (n=116) which are typical
      estrogen-dependent tumors. Breast cancers were divided into two groups, ER
      positive and ER-negative, according to the ER status determined by enzyme
      immunoassay. ER-alpha mRNA levels were significantly (P<0.01) higher in ER
      positive (679.4+/-74.7 fmol/microg RNA) than ER-negative (159.7+/-33.4) breast
      cancers, and pancreatic cancers showed significantly (P<0.01) lower ER-alpha mRNA
      levels (17.5+/-10.0) than ER-negative breast cancers. On the other hand, ER-beta
      mRNA levels were significantly (P<0.01) higher in ER-negative (14.1+/-1.6) than
      ER-positive breast cancers (7.9+/-1.0), and pancreatic cancers showed
      significantly (P<0.01) higher ER-beta mRNA levels (28.1+/-5.1) than ER-negative
      breast cancers. Accordingly, ER-alpha/ER-beta mRNA ratios were significantly
      (P<0.01) lower in pancreatic cancers (0.94+/-053) than in ER-positive (203.9+/
      34.5) and ER-negative (21.9+/-5.2) breast cancers. ER-beta2 mRNA variant
      expression was significantly (P<0.05) higher in pancreatic cancers than in ER
      positive and ER-negative breast cancers, and, on the contrary, ER-beta1 mRNA
      variant expression was significantly (P<0.01) lower in pancreatic cancers than in
      ER-positive and ER-negative breast cancers. These results suggest a possibility
      that ER-beta (ER-beta2) plays a more important role than ER-alpha in pancreatic
      cancers.

PMID- 11448540
TI  - Lippia: traditional uses, chemistry and pharmacology: a review.
AB  - The chemical composition, pharmacological activity and traditional uses of 52
      species attributed to the genus Lippia (Verbenaceae) as used in the South and
      Central America, and Tropical Africa, were revised and compared. A survey of the
      available literature shows that these species are used mostly for the treatment
      of gastrointestinal and respiratory disorders and as seasoning. Additionally,
      some of these Lippia species showed antimalarial, spasmolitic, sedative,
      hypotensive and, anti-inflammatory activities. Generally, the essential oil or
      the phenolic compounds (flavonoids) from these plant extracts are assumed to be
      the active principles.

PMID- 11448541
TI  - Effects of the aqueous and methylene chloride extracts of Bidens pilosa leaf on
      fructose-hypertensive rats.
AB  - We investigated the effects of the aqueous (150-350 mg/kg) and methylene chloride
      (150-300 mg/kg) extracts of Bidens pilosa on fructose-induced hypertension in
      rats. Food and liquid intake were measured as well as systolic blood pressure and
      plasma levels of glucose, insulin, cholesterol, triglycerides and creatinine.
      Fructose feeding for 6 weeks induced hypertension, hyperinsulinemia and increased
      plasma triglyceride levels in male Wistar rats. The aqueous and methylene
      chloride extracts of B. pilosa reversed the high blood pressure and
      hypertriglyceridemia developed due to fructose feeding but did not have any
      effects on plasma levels of insulin and glucose. High doses of the extracts
      reduced plasma creatinine levels and tended to increase plasma cholesterol. These
      results suggest that the extracts of B. pilosa possess hypotensive effects whose
      mechanism of action is not related to insulin sensitivity.

PMID- 11448542
TI  - Neuropharmacological profile of ethnomedicinal plants of Guatemala.
AB  - We carried out the Irwin's test with some different extracts of the aerial parts
      of Thidax procumbens L., the leaves of Neurolaena lobata (L.) R. Br., bark and
      leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp.,
      and root and leaves of Petiveria alliacea L. At dosage of 1.25 g dried plant/kg
      weight aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth.
      and Gliricidia sepium Jacq. Walp. demonstrated the most activity: decrease in
      motor activity, back tonus, reversible parpebral ptosis, catalepsy and strong
      hypothermia. These extracts of both plants were assayed for effects on CNS and
      they caused very significant reductions in spontaneous locomotor activity,
      exploratory behavior and rectal temperature and they increased the sodium
      pentobarbital-induced sleeping time.

PMID- 11448543
TI  - Effect of garlic (Allium sativum L.) extract on tissue lead level in rats.
AB  - The prophylactic efficacy of garlic (Allium sativum L.) extract to reduce tissue
      lead (Pb) concentration was evaluated experimentally in rats. Thirty female rats
      were divided into five groups, keeping group A as a healthy control. Rats of
      groups B, C, D and E received lead acetate orally at the rate of 5 mg per kg body
      weight daily for 6 weeks. The garlic extract was tried in three doses, viz. 100
      (low), 200 (medium) and 400 mg (high) per kg body weight orally and given
      simultaneously with lead salt to the rats of group C, D and E, respectively. Mean
      blood lead concentrations in lead-exposed rats ranged between 0.13+/-0.02 and
      0.96+/-0.06 microg/ml, whereas in garlic-treated rats, the range was between
      0.16+/-0.01 and 0.80+/-0.05; 0.13+/-0.01 and 0.71+/-0.06 and 0.14+/-0.01 and
      0.60+/-0.05 microg per ml in low, medium and high dose groups, respectively. The
      mean lead concentration in liver, kidneys, brain and bone of lead exposed rats
      was 2.943+/-0.206, 4.780+/-0.609, 1.019+/-0.100 and 44.075+/-2.60 microg per ml,
      respectively. Concomitant use of garlic extract at the three different doses was
      found to reduce lead concentration considerably indicating the potential
      therapeutic activity of garlic against lead.

PMID- 11448544
TI  - Traditional Indian anti-diabetic plants attenuate progression of renal damage in
      streptozotocin induced diabetic mice.
AB  - The purpose of the study was to investigate the effects of daily oral feeding
      Momordica charantia (MC) (200 mg/kg), Eugenia jambolana (EJ) (200 mg/kg), Mucuna
      pruriens (MP) (200 mg/kg) and Tinospora cordifolia (TC) extracts for 40 days on
      blood glucose concentrations and kidney functions in streptozotocin (STZ)
      diabetic rats. Plasma glucose levels, body weight, urine volume and urinary
      albumin levels were monitored on every 10th day over a 40-day period while plasma
      creatinine levels were assessed at the beginning and end of experiment. Renal
      hypertrophy was assessed as the ratio between the kidney weight and total body
      weight. Plasma glucose concentrations in STZ-diabetic mice were reduced by the
      administration of extracts of MC, EJ, TC and MP by 24.4, 20.84, 7.45 and 9.07%,
      respectively (P<0.005 for MC, EJ, MP and P<0.05 for TC). Urine volume was
      significantly higher (P<0.005) in diabetic controls and MC, EJ, MP and TC
      treatment prevented polyuria (P<0.001, 0.0001, 0.01 and 0.001, respectively).
      After 10 days of STZ administration urinary albumin levels (UAE) were over 6 fold
      higher in diabetic controls as compared to normal controls. Treatment with MC,
      EJ, MP and TC significantly prevented the rise in UAE levels from day 0 to 40 in
      comparison to diabetic controls (P<0.0001, 0.0001, 0.05, 0.05, respectively).
      Renal hypertrophy was significantly higher in diabetic controls as compared to
      non-diabetic controls. MC and EJ partially but significantly (P<0.05) prevented
      renal hypertrophy as compared to diabetic controls. TC and MP failed to modify
      renal hypertrophy. Results indicate that these plant drugs should be studied
      further.

PMID- 11448545
TI  - In vitro antiplasmodial activity and cytotoxicity of ethnobotanically selected
      South African plants.
AB  - The resistance of Plasmodium spp. to currently used drugs has become a serious
      problem and efforts are being directed in obtaining new drugs with different
      structural features. One option favoured is the search for new plant derived
      antimalarial drugs. Bark and leaves of 20 extracts from 14 South African plant
      species were tested for in vitro antiplasmodial activity by means of the flow
      cytometric test. The most active extract of each species giving more than 70%
      inhibition at 50 microg/ml was selected for determination of IC(50) values. Two
      extracts had IC(50) values below 2 microg/ml, another seven had IC(50) values
      between 2 and 5 microg/ml while one had an IC(50) of 10.1 microg/ml. Chloroquine
      had an IC(50) of 0.043 microg/ml. Cytotoxicities of the five most active extracts
      at 50 microg/ml were determined with the monkey kidney cell toxicity test and the
      ID(50) values ranged between 35 and 100 microg/ml.

PMID- 11448546
TI  - Effects of Sclerocarya birrea (A. rich) hochst (anacardiaceae) leaf extracts on
      calcium signalling in cultured rat skeletal muscle cells.
AB  - Sclerocarya birrea is a plant used widely to treat many diseases in Burkina Faso,
      although no scientific data has been reported about its mechanism of action. In
      the present study the effects of its leaf extracts were investigated on calcium
      signalling in rat cultured skeletal muscle cells. The results show that the
      different extracts (crude decoction, aqueous, ethanolic and chloroformic
      extracts) have significant antagonistic effect on caffeine-induced calcium
      release from sarcoplasmic reticulum. Crude decoction is the most active followed
      by ethanolic, aqueous and chloroformic extracts in dose-dependent manner and can
      partly justify the use of the plant in traditional medicine.

PMID- 11448547
TI  - Influence of Podophyllum hexandrum on endogenous antioxidant defence system in
      mice: possible role in radioprotection.
AB  - Podophyllum hexandrum, a Himalayan herb with known radioprotective and anti
      tumour properties, was investigated for its mechanism of action. Glutathione S
      transferase (GST), catalase, superoxide dismutase (SOD) activities and lipid
      peroxidation (LPx) were determined in the liver, jejunum and ileum at various
      time intervals, with and without the aqueous extract of P. hexandrum rhizome (200
      mg/kg b.w. i.p.) in unirradiated and whole body irradiated (10 Gy,-2 h) male
      Swiss albino mice. Pre-irradiation treatment with P. hexandrum enhanced liver GST
      (P<0.01) and SOD (P<0.05) at 12 h post irradiation, the intestinal SOD
      (P<0.00005) at 84 h post irradiation was significantly elevated. However, no
      significant change was manifested in the catalase activity in the liver, at any
      of the post irradiation intervals (0, 12 and 84 h). The antioxidant defence with
      Podophyllum sp. treatment in mice can explain to some extent its protective
      action manifested in terms of survival against whole body lethal irradiation.
      However, some other possible mechanisms that may strengthen radioprotective
      action of the Podophyllum sp. extract need to be investigated further.

PMID- 11448548
TI  - Plants used as abortifacients in the Sangmelima region of Southern Cameroon.
AB  - Twenty species from 16 plant families used to induce abortion in the Sangmelima
      region (South Province of Cameroon) are reported with local names, modes of uses
      and their side effects, if known, with a discussion on pharmacological effect
      based on published experimental literature.

PMID- 11448549
TI  - Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in
      streptozotocin induced diabetic rats.
AB  - Hypoglycemic activity was detected in dichloromethane:methanol extract (1:1) of
      leaves and twigs of Catharanthus roseus (family Apocynaceae), a traditionally
      used medicinal plant, using streptozotocin (STZ) induced diabetic rat model.
      Extract at dose 500 mg/kg given orally for 7 and 15 days showed 48.6 and 57.6%
      hypoglycemic activity, respectively. Prior treatment at the same dose for 30 days
      provided complete protection against STZ challenge (75 mg/kg/i.p.x1). Enzymic
      activities of glycogen synthase, glucose 6-phosphate-dehydrogenase, succinate
      dehydrogenase and malate dehydrogenase were decreased in liver of diabetic
      animals in comparison to normal and were significantly improved after treatment
      with extract at dose 500 mg/kg p.o. for 7 days. Results indicate increased
      metabolization of glucose in treated rats. Increased levels of lipid peroxidation
      measured as 2-thiobarbituric acid reactive substances (TBARS) indicative of
      oxidative stress in diabetic rats were also normalized by treatment with the
      extract.

PMID- 11448550
TI  - A pharmacological study of Cecropia obtusifolia Bertol aqueous extract.
AB  - Cecropia obtusifolia (Cecropiaceae) is a species from tropical America and its
      leaves are used in traditional medicine for the treatment of diabetes and as an
      anti-inflammatory agent. In the present study, the analgesic, anti-inflammatory
      and central nervous system depressant effects of the aqueous extract from the
      leaves of C. obtusifolia were investigated in different experimental models, with
      the purpose of validating its ethnomedical uses. The results obtained with the
      extract from the leaves of C. obtusifolia reflect a low toxicity, a substantial
      central depressor effect and analgesic activity and significant motor
      incoordination and muscle relaxant activity. Concerning the analgesic activity,
      using the hot plate test, the extract did not produce any effect, however it
      showed a significant effect on the pain induced by chemical stimuli (acetic and
      formalin test); this suggests the peripheral analgesic effect of the extract. The
      extract also showed a topical and systemic anti-inflammatory effect. Thus this
      work could justify the popular use of C. obtusifolia in rheumatic and kidney
      inflammation pathologies and reveals that this plant is an interesting species.

PMID- 11448551
TI  - Antioxidant potential of two polyherbal. preparations used in Ayurveda for the
      treatment of rheumatoid arthritis.
AB  - Reactive oxygen intermediates (ROI) are together with prostanoids, leukotrienes
      and proteases, believed to be the mediators of inflammation and responsible for
      the pathogenesis of tissue destruction in RA. Antioxidant (AO) activity is one of
      the mechanisms by which many conventional drugs used in day to day treatment of
      RA alleviate the painful symptoms associated with this disease. An investigation
      has been carried out to compare the antioxidant potentials of two polyherbal
      formulations, Maharasnadhi quathar (MRQ) and Weldehi choornaya (WC), used by
      Ayurvedic medical practitioners in Sri-Lanka for the treatment of RA patients. AO
      potentials of these preparations were assessed by their effects in RA patients
      on: (a) activities of the AO enzymes superoxide dismutase (SOD), glutathione
      peroxidase (GPX) and catalase; (b) lipid peroxidation (as estimated by
      thiobarbituric acid reacting substances (TBARS) generation); and (c)
      concentrations of serum iron and haemoglobin (Hb), and the total iron binding
      capacity (TIBC). The overall results of the study demonstrate that MRQ has much
      greater AO potential than WC. Thus, on treatment with MRQ for 3 months, the
      initial activities of plasma SOD, GPX and catalase, were enhanced by 44.6, 39.8
      and 25.2%, respectively. There was no significant improvement in any of these
      enzyme activities in patients treated with WC for the same time period as MRQ.
      Although the extent of lipid peroxidation in plasma of RA patients could be
      decreased by both drug preparations, the reduction mediated in 3 months by MRQ
      (34%) was markedly greater than that due to WC (21.8%). The total serum iron and
      Hb concentrations and TIBC in the RA patients included in the study could be
      significantly improved by treatment with MRQ but not by WC. Thus, at the end of 3
      months treatment with MRQ, concentrations of the total serum iron and Hb, and the
      TIBC of patients improved by 26.8, 24.8 and 16.1%, respectively. Possible reasons
      for differences in the AO potentials of MRQ and WC are discussed.

PMID- 11448552
TI  - Ethnomedicinal and obnoxious grasses of Rajasthan, India.
AB  - The present communication is an account of 24 ethnomedicinal and 10 obnoxious
      grasses of Rajasthan. The ethnomedicinal grasses are used by forest dwellers for
      various ailments in their daily life. In spite of the fact that certain grasses
      are of high medicinal value, some grasses are also alleged to be obnoxious. These
      obnoxious grasses hamper the economic balance of tribal as well as rural
      communities. The necessity to popularise the identity and utility of grasses and
      the need to build up a database on local knowledge/information held by tribes is
      stressed. Local name, Botanical name, plant parts used, causing injuries and
      methods of application or administration are given.

PMID- 11448553
TI  - The effect of fennel essential oil on uterine contraction as a model for
      dysmenorrhea, pharmacology and toxicology study.
AB  - Increasing the ectopic uterine motility is the major reason for primary
      dysmenorrhea. This motility is the basis for several symptoms including for pain
      is the main complaints of patients with primary dysmenorrhea. There are several
      mechanisms, which initiate dysmenorrhea. Therefore, different compounds can be
      employed to control its symptoms. In long-term therapy, combination of oestrogens
      and progestins may be useful. In short-term therapy, dysmenorrhea sometimes non
      steroidal anti-inflammatory drugs (NSAIDs) are used. Most of NSAIDs in long-term
      therapy show severe adverse effects. In an attempt to find agents with less
      adverse effect the fennel essential oil (FEO) was chosen for this investigation.
      In this article, effects of FEO on the uterine contraction and estimation of
      LD(50) in rat were described. For assessment of pharmacological effects on the
      isolated rat uterus, oxytocin (0.1, 1 and 10 mu/ml) and prostaglandin E(2)
      (PGE(2)) (5x10(-5) M) were employed to induce muscle contraction. Administration
      of different doses of FEO reduced the intensity of oxytocin and PGE(2) induced
      contractions significantly (25 and 50 microg/ml for oxytocin and 10 and 20
      microg/ml PGE(2), respectively). FEO also reduced the frequency of contractions
      induced by PGE(2) but not with oxytocin. LD(50) of FEO was obtained in the female
      rats by using moving average method. The estimated LD(50) was 1326 mg/kg. No
      obvious damage was observed in the vital organs of the dead animals.

PMID- 11448554
TI  - Antibacterial activity of Marula (Sclerocarya birrea (A. rich.) Hochst. subsp.
      caffra (Sond.) Kokwaro) (Anacardiaceae) bark and leaves.
AB  - Marula bark is widely used for bacteria-related diseases by indigenous cultures
      in Africa. This study was undertaken to investigate whether the ethnobotanical
      use can be validated by laboratory studies. Bark and leaves were extracted with
      acetone and MIC values were determined using a microplate serial dilution
      technique with Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli
      and Enterococcus faecalis as test organisms. All extracts were active with MIC
      values from 0.15 to 3 mg/ml. Based on minimum inhibitory concentration values,
      inner bark extracts tended to be the most potent followed by outer bark and leaf
      extracts, but the differences were not statistically significant. There were two
      major bioactive components visible after bioautography of leaf extracts: one
      strongly polar and the other highly non-polar. The bioactive components could be
      separated from 92% of the non-active dry matter by solvent-solvent fractionation
      into the carbon tetrachloride, chloroform and n-butanol fractions; these
      fractions, however, still contained many different compounds. Using bark may be
      detrimental to the plant, but leaf material can also be used for antibacterial
      application.

PMID- 11448556
TI  - Emergence of methicillin-resistant Staphylococcus aureus as a community pathogen.
AB  - Methicillin-Resistant Staphylococcus aureus (MRSA) infection is an established
      nosocomial pathogen, with hospital-based outbreaks occurring worldwide. An
      increase in MRSA infections without risk factors has been recently documented in
      several reports. A prospective study was conducted over a 36-month period to
      determine the prevalence and risk factors for community-acquired MRSA infection
      at King Fahad Hospital of the University Al-Khobar, Saudi Arabia. Patients
      hospitalized within the previous 12 months or transfers from hospitals or nursing
      homes were excluded. The number of patients with community-acquired MRSA disease
      increased from a single patient in 1998 to fifteen patients in the year 2000 and
      the percentage of community-acquired MRSA/total number of MRSA increased from 5%
      to 33%. Fifteen (75%) of 20 patients with community-acquired MRSA infection had
      no discernible characteristics of MRSA infections. Skin and soft tissue
      infections were the predominant presentation. Most MRSA isolates (95%) were
      susceptible to multiple antibiotics. Our data suggest that MRSA is an emerging
      community pathogen. Hospital infection control strategies will have to be
      redefined and community approaches developed to reduce transmission.

PMID- 11448557
TI  - Comparison of the Velogene Rapid MRSA Identification Assay, Denka MRSA-Screen
      Assay, and BBL Crystal MRSA ID System for rapid identification of methicillin
      resistant Staphylococcus aureus.
AB  - Early detection of methicillin-resistant S.aureus (MRSA) is critical for both the
      management of infected patients, and the timely institution of appropriate
      infection control measures. Although detection of the mecA gene by PCR remains
      the gold standard, this technology is inaccessible for many laboratories.
      Therefore, we sought to evaluate several new rapid identification systems and
      compare them to PCR. A total of 71 methicillin-susceptible S. aureus (MSSA), 25
      borderline oxacillin-resistant S. aureus (BORSA), and 213 MRSA were selected for
      study. S.aureus was identified using standard methods. Initial screening was
      performed on a Mueller-Hinton agar plate with 6 mg/L of oxacillin. MRSA strains
      were identified using PCR with primers specific for the mecA gene. PCR was used
      as the reference method. All isolates were tested using the BBL Crystal MRSA ID
      System (Becton Dickinson Microbiology Systems, Maryland, USA), the MRSA-Screen
      Assay (Denka Seiken Co., Ltd., Tokyo, Japan), and the Velogene Rapid MRSA
      Identification Assay (ID Biomedical Corp, Vancouver, BC). With minor
      modifications, all assays were performed according to manufacturers'
      instructions. Overall, the 3 commercial assays performed well. The sensitivity
      and specificity of the BBL, Denka, and Velogene systems were 99%/100%, 99%/100%,
      and 96%/100% respectively. The advantages of the phenotypic tests-BBL Crystal Kit
      and Denka MRSA-Screen Assay include lower cost per test, shelf-life, ease of use,
      and rapid turn-around times. Advantages of the Velogene Rapid MRSA include
      ability to perform genotypic high-volume testing without the equipment
      requirements and technical complexity involved with PCR. Turn-around times ranged
      from 15 min for the Denka MRSA-Screen Assay, 2 h for the Velogene Rapid MRSA, and
      4 h for the BBL Crystal. The BBL Crystal, Denka MRSA-Screen, and Velogene Rapid
      MRSA identification systems are rapid, easy to perform, and provide accurate
      identification of MRSA. These rapid kits offer an acceptable alternative for
      smaller, non-reference, laboratories and reduce the dependency on PCR in larger
      laboratories for routine confirmation.

PMID- 11448558
TI  - Development of a ceuE-based multiplex polymerase chain reaction (PCR) assay for
      direct detection and differentiation of Campylobacter jejuni and Campylobacter
      coli in Thailand.
AB  - A novel ceuE-based multiplex PCR system was developed as an efficient diagnostics
      test to detect and differentiate C. jejuni and C. coli. There is no cross
      reactivity between C. jejuni and C. coli. In addition, the assay does not produce
      a positive signal from other enteric bacteria including Salmonella, Shigella and
      Escherichia coli strains. Campylobacter detection sensitivity was determined to
      be equivalent to previously reported PCR for other enteric bacteria. We also
      noticed that silicon dioxide extraction can improve Campylobacter detection
      sensitivity from infected stool samples. It was demonstrated that the PCR assay
      developed in this study had a much better Campylobacter detection rate than the
      traditional culturing method (77% versus 56%). However, we also identified small
      numbers of culture positive stools (8%, or 16 out of 202 samples) that did not
      yield PCR positive results for Campylobacter. These PCR negative/culture positive
      stools were proven to be inhibitory to PCR amplification.

PMID- 11448559
TI  - Comparison of SeroMP IgA with four other commercial assays for serodiagnosis of
      Mycoplasma pneumoniae pneumonia.
AB  - Acute phase serum samples from 23 patients with Mycoplasma pneumoniae pneumonia
      were examined for specific antibodies with microparticle agglutination (MAG)
      assay, complement fixation (CF)-test, IgM-specific ELISA, and Immunocard-based
      IgM-EIA. A novel 3-h IgA-ELISA (SeroMP-IgA) was tested to assess its diagnostic
      value. For MAG, CF, IgM-ELISA, card-based IgM-EIA, and IgA-ELISA positive results
      were obtained in 87%, 87%, 91%, 87%, and 100%, respectively. Overall concordance
      was 78%. Specificity testing of 46 healthy blood donors revealed an optimal
      diagnostic cut-off range of 22-30 IgA-ELISA binding units (BU)/mL resulting in
      91%-100% specificity and 100%-96% sensitivity for serologic diagnosis of acute M.
      pneumoniae infection.

PMID- 11448560
TI  - A two year global evaluation of the susceptibility of Candida species to
      fluconazole by disk diffusion.
AB  - The in-vitro activity of fluconazole against 46,831 yeast isolates collected over
      a two-year period from 57 laboratories in 33 countries worldwide was assessed
      using a disc diffusion method. Candida albicans was the organism isolated most
      frequently, accounting for 68.6% of the total number of isolates. C. glabrata, C.
      tropicalis, C parapsilosis and C. krusei and Cryptococcus neoformans represented
      9.9, 4.7, 4.3, 1.9, and 1.4% of isolates respectively during the 2 year period
      and rates varied markedly between countries. In 1999 data blood isolates
      represented 4.9% of all isolates and intensive care unit isolates represented
      9.9%. In both the 1998 and 1999 data, 99% of C. albicans were fully susceptible
      (S) to fluconazole, and 95.6% of all species of yeasts tested were S or
      susceptible-dose dependent (S-DD) to fluconazole. No emerging trends of
      resistance were noted with any of the Candida spp. tested as 96% of all isolates
      retained susceptibility (S or S-DD) to this agent.

PMID- 11448561
TI  - In vitro activity of ABT-773 versus macrolides and quinolones against resistant
      respiratory tract pathogens.
AB  - ABT-773, a novel ketolide, was compared to erythromycin, azithromycin,
      clarithromycin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin,
      gatifloxacin, and gemifloxacin against antibiotic-resistant strains recently
      isolated from patients with respiratory tract infections. MICs were determined by
      agar dilution using standard NCCLS methodology. ABT-773 (MIC(90) 0.06 mg/L) was
      more active than the macrolides (MIC(90) > or = 2 mg/L) and fluoroquinolones
      (MIC(90) > or = 0.5 mg/L) against penicillin-resistant Streptococcus pneumoniae.
      The fluoroquinolones were the most active agents tested against beta-lactamase
      positive Haemophilus influenzae (MIC(90) < or = 0.01-0.06 mg/L), against which
      ABT-773 (MIC(90) 4 mg/L) was comparable to azithromycin and two- and four-fold
      more active than erythromycin and clarithromycin, respectively. Against beta
      lactamase positive Moraxella catarrhalis, the activity of ABT-773 (MIC(90) 0.06
      mg/L) was comparable to gemifloxacin, trovafloxacin, levofloxacin, and
      ciprofloxacin (MIC(90) 0.03-0.06 mg/L) and 4- to eightfold greater than that of
      clarithromycin, gatifloxacin, and erythromycin. These data suggest ABT-773 could
      be a valuable compound for the treatment of respiratory tract infections,
      including those resistant to usual oral therapy.

PMID- 11448562
TI  - Activity of cefepime, cefotaxime, ceftazidime, and aztreonam against extended
      spectrum-producing isolates of Klebsiella pneumoniae and Escherichia coli from
      Chilean hospitals.
AB  - Resistance of Gram-negative bacilli to third-generation cephalosporins has been
      increasing due to the production of extended-spectrum beta-lactamases. In this
      work, the activities of cefepime, cefotaxime, ceftazidime, and aztreonam, alone
      and in association with clavulanic acid, against isolates of Klebsiella
      pneumoniae and Escherichia coli are compared. These isolates produce extended
      spectrum beta-lactamases as shown by the synergy tests and by the decrease in the
      MICs of cephalosporins in the presence of clavulanic acid. Cefepime was the most
      active compound against these microorganisms. In addition, the microorganisms
      exhibited lower frequencies of resistance to this cephalosporin.

PMID- 11448563
TI  - Activity of BMS284756 (T-3811) tested against anaerobic bacteria, Campylobacter
      jejuni, Helicobacter pylori and Legionella spp.
AB  - BMS284756, a novel des-fluoro (6) quinolone (formerly T-3811), was tested for
      activity and spectrum using reference agar dilution (AD) and Etest (AB BIODISK,
      Solna, Sweden) methods. The antimicrobial activities of BMS284756, ciprofloxacin,
      gatifloxacin, levofloxacin, and trovafloxacin were evaluated against
      Campylobacter jejuni (38 strains), Helicobacter pylori (21 strains), Legionella
      spp. (66 strains), and 197 anaerobic isolates. BMS284756 (MIC(90), 0.008
      microg/mL) was four-fold more active than gatifloxacin and trovafloxacin against
      H. pylori strains. Gatifloxacin and BMS284756 (MIC(50), 0.03 microg/mL) were > or
      = two-fold more active than levofloxacin against C. jejuni, but their spectrums
      were judged equivalent overall (89.4% susceptible). Against the Legionella spp.,
      ciprofloxacin and levofloxacin (MIC(90), 0.25 microg/mL) had two-fold greater
      activity compared to gatifloxacin or BMS284756, but all strains were considered
      inhibited at clinically achievable levels. BMS284756 and trovafloxacin (MIC(90),
      2 and 4 microg/mL, respectively) were four-to-eight-fold more potent than other
      comparators against the Gram-negative anaerobic species. Against the Gram
      positive anaerobes (dominated by Clostridium difficile; 61 strains), BMS284756
      activity was generally reduced, but equivalent or superior to trovafloxacin (68%
      inhibited at < or = 4 microg/mL). Inter-method comparisons (Etest versus AD) of
      BMS284756 MIC values showed a high correlation for C. jejuni and anaerobes (93.3
      to 97.6% +/- two log (2) dilution steps). In conclusion, BMS284756 was very
      active against C. jejuni, H. pylori, Legionella spp. and most anaerobes, thus the
      potential role of this des-fluoro compound for treatment of infections caused by
      these fastidious species warrants further investigation.

PMID- 11448564
TI  - Comparative in vitro activity of gemifloxacin, ciprofloxacin, levofloxacin and
      ofloxacin in a North American surveillance study.
AB  - The in vitro activity of gemifloxacin, a new fluoroquinolone, was compared to
      three marketed fluoroquinolones; ciprofloxacin, levofloxacin and ofloxacin
      against over 4,000 recent clinical isolates covering 29 species isolated in the
      United States and Canada between 1997-1999. Based on MIC(90)s, gemifloxacin was
      the most potent fluoroquinolone tested against a majority of Gram-positive
      isolates: Streptococcus pneumoniae, penicillin resistant S. pneumoniae, macrolide
      resistant S. pneumoniae, ciprofloxacin non-susceptible (MIC > or = 4 microg/mL)
      S. pneumoniae, S. pyogenes, S. agalactiae, viridans streptococci, Enterococcus
      faecalis, methicillin susceptible Staphylococcus aureus, methicillin resistant S.
      aureus, S. epidermidis, S. hemolyticus, and S. saprophyticus. Against
      Enterobacteriaceae and aerobic non-Enterobacteriaceae Gram-negatives,
      gemifloxacin was usually comparable to ciprofloxacin and levofloxacin and more
      potent than ofloxacin for the following species: Citrobacter freundii,
      Enterobacter aerogenes, E. cloacae, Escherichia coli, Klebsiella oxytoca,
      Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, P. vulgaris,
      Providencia stuartii, Serratia marcescens, Acinetobacter lwoffii, A. baumannii,
      Burkholderia cepacia, Haemophilus influenzae, H. parainfluenzae, Moraxella
      catarrhalis, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia.
      Gemifloxacin was generally 16-64 fold more potent than the other fluoroquinolones
      tested against Gram-positive organisms and retains excellent activity comparable
      with ciprofloxacin and levofloxacin against a majority of Gram-negative
      pathogens.

PMID- 11448565
TI  - Multi-laboratory assessment of the linezolid spectrum of activity using the Kirby
      Bauer disk diffusion method: Report of the Zyvox Antimicrobial Potency Study
      (ZAPS) in the United States.
AB  - The in vitro activity of linezolid against common Gram-positive pathogens was
      compared to that of penicillin or ampicillin or oxacillin (depending upon genus),
      cefazolin, erythromycin, clindamycin, quinupristin/dalfopristin, levofloxacin,
      nitrofurantoin and vancomycin by disk diffusion methods. One hundred and six
      centers (31 states in US) tested recent clinical isolates of Staphylococcus
      aureus, coagulase-negative staphylococci, Enterococcus faecium, E. faecalis,
      Streptococcus pneumoniae, and other streptococci. Testing was conducted using the
      standardized disk diffusion method and concurrent quality control testing was
      performed. Strains with linezolid zone diameters of < or = 20 mm were requested
      for referral to the microbiology monitor for confirmation. A total of 3,100
      isolates (97% compliance) were tested. Susceptibility (zone diameters, > or = 21
      mm) of staphylococci and streptococci to linezolid was reported in 100% and 99.4%
      of staphylococci and streptococci, respectively. Susceptibility (zone diameters,
      > or = 23 mm) of enterococci to linezolid was 96.0% with only three isolates
      (0.4%) reported as resistant (zone diameters, < or = 20 mm; unconfirmed). Among a
      total of nine isolates (0.3%) reported to have zone diameters 20 mm, six were not
      submitted for further testing, two were contaminated with Gram-negative bacilli
      and one was determined to be linezolid-susceptible. There were no differences in
      linezolid susceptibility in the vancomycin- or oxacillin- or penicillin-resistant
      subsets of strains. This susceptibility pattern for US medical centers is
      indicative of the excellent and nearly complete in vitro activity against the key
      Gram-positive pathogens for which linezolid has received US Food and Drug
      Administration indications for clinical use.

PMID- 11448566
TI  - Proposed quality control guidelines for National Committee for Clinical
      Laboratory Standards Susceptibility Tests using the veterinary antimicrobial
      agent tiamulin.
AB  - Quality control guidelines for standardized antimicrobial susceptibility test
      methods are critical for the continuing accuracy of these clinical tests. In this
      report, quality control limits were proposed for the veterinary antimicrobial
      agent tiamulin with minimum inhibitory concentration (MIC) ranges of three or
      four log(2) dilution steps in two different medium formulations. Disk diffusion
      zone diameter ranges were proposed for tiamulin tested against Actinobacillus
      pleuropneumoniae ATCC 27090 (12-18 mm) and Staphylococcus aureus ATCC 25923 (25
      32 mm). The data from eight participating laboratories produced 100% of results
      within proposed MIC limits (8-32 microg/mL), and 95.8-97.0% of zones were found
      within suggested zone diameter QC guidelines. These proposed QC ranges should be
      validated by in-use results from veterinary clinical laboratories.

PMID- 11448567
TI  - Validation of cefditoren MIC quality control ranges by a multi-laboratory study
      (2001).
AB  - The potency of cefditoren has been well documented to include broad coverage
      against both Gram-positive and Gram-negative organisms including species causing
      community-acquired respiratory tract infections. The accuracy of in vitro test
      results has been questioned due to debate over inconsistencies in quality control
      (QC) recommendations published by the National Committee for Clinical Laboratory
      Standards (NCCLS). Previous studies have recommended conflicting and generally
      broad MIC dilution ranges for several commonly used QC organisms. This study used
      NCCLS recommended guidelines to re-evaluate the MIC ranges using a seven
      laboratory M23-A2 design. The results of this multi-laboratory investigation
      leads to the proposal of the following QC range recommendations for cefditoren:
      Streptococcus pneumoniae ATCC 49619 (0.016-0.06 microg/mL); Haemophilus
      influenzae ATCC 49247 (0.06-0.25 microg/mL); Escherichia coli ATCC 25922 (0.12-1
      microg/mL); and Staphylococcus aureus ATCC 29213 (0.25-1 microg/mL). These
      proposed ranges validate those suggested previously for E. coli and the
      problematic H. influenzae, but a three log(2) dilution range may be sufficient
      for S. aureus and S. pneumoniae.

PMID- 11448568
TI  - Parasitic screening of a refugee population in Illinois.
AB  - In a one year period in Illinois, 4,695 stool specimens from refugees for
      parasitologic screening and 733 diarrheal specimens from non-refugees were tested
      by routine ova and parasite examination- concentration and permanent stained
      smear. Patients infected with pathogens were as follows: African group (48.9%),
      Middle Eastern group (56.5%), Southeast Asian group (48.9%), Eastern European
      group (46.6%), Hispanic group (38.0%) and non-refugee group (20.7%). The study
      showed differences between the various groups of refugees and the non-refugee
      group. The need for routine screening of this population was clearly shown.

PMID- 11448569
TI  - Influence of apolipoprotein-E phenotypes on postprandial lipoprotein metabolism
      after three different fat loads.
AB  - The aim of this study was to evaluate the postprandial response to three fat
      loading tests in healthy subjects with different apolipoprotein E (apoE)
      phenotypes. Thirty-four subjects were studied: 15 with apoE3/3 (7 men and 8
      women), 12 with apoE4/3 (5 men and 7 women), and 7 with apoE2/3 (4 men and 3
      women). All received three oral fat loads at 1-wk intervals in meals rich in
      monounsaturated fatty acid, polyunsaturated fatty acid, and saturated fatty acid,
      with retinyl palmitate (60000 IU/m(2) of aqueous vitamin A) to quantify
      lipoproteins secreted by the intestine. No significant differences in
      postprandial lipoproteins were found between the three different fat loads. Peaks
      and incremental areas under the curve of retinyl palmitate in non-chylomicron
      fractions were higher in the apoE2/3- than in the apoE3/3- and apoE4/3-phenotype
      groups in meals rich in monounsaturated and polyunsaturated fatty acids (P <
      0.05). When the three fat loads were analyzed together, the incremental area
      under the curve of retinyl palmitate was much higher in the apoE2/3- than in the
      other apoE-phenotype groups (P = 0.0004). In conclusion, the magnitude of
      intestinal lipoproteins after fat load, especially with monosaturated and
      polyunsaturated fatty acids, is higher in subjects with apoE2/3 than in those
      with apoE3/3 and apoE4/3 phenotypes.

PMID- 11448570
TI  - Fat-free and fat mass percentiles in 5225 healthy subjects aged 15 to 98 years.
AB  - OBJECTIVES: Fat-free mass (FFM) and fat mass (FM) are important in the evaluation
      of nutritional status. Bioelectrical impedance analysis (BIA) is a simple,
      reproducible method used to determine FFM and FM. Because normal values for FFM
      and FM have not yet been established in adults aged 15 to 98 y, its use is
      limited in the evaluation of nutritional status. The aims of this study were to
      determine reference values for FFM, FM, and percentage of FM by BIA in a white
      population of healthy adults, observe their differences with age, and develop
      percentile distributions for these parameters between ages 15 and 98 y. METHODS:
      Whole-body resistance and reactance of 2735 healthy white men and 2490 healthy
      white women, aged 15 to 98 y, was determined by 50-kHz BIA, with four skin
      electrodes on the right hand and foot. FFM and FM were calculated by a previously
      validated, single BIA formula and analyzed for age decades. RESULTS: Mean FFM
      peaked in 35- to 44-y-old men and 45- to 54-y-old women and declined thereafter.
      Mean FFM was 8.9 kg or 14.8% lower in men older than 85 y than in men 35 to 44 y
      old and 6.2 kg or 14.3% lower in women older than 85 y than in women 45 to 54 y
      old. Mean FM and percentage of FM increased progressively in men and women
      between ages 15 and 98 y. The results suggested that the greater weight noted in
      older subjects is due to larger FM. CONCLUSIONS: The percentile data presented
      serve as reference to evaluate deviations from normal values of FFM and FM in
      healthy adult men and women at a given age.

PMID- 11448571
TI  - Effect of a moderately energy-restricted diet on obese patients with fatty liver.
AB  - The effects of a moderately energy-restricted (25 kcal/kg) diet on liver-function
      tests, anthropometric measurements, mononuclear-cell phospholipid fatty acid,
      lymphocyte blastogenesis, and plasma prostaglandin E2 and alpha-tocopherol levels
      were observed at weeks 0, 8, and 24 in 14 obese patients with fatty liver. Serum
      aminotransferase levels were improved significantly, with decreases in the body
      mass index and waist circumference. Decreases in energy intake from carbohydrate
      and increases in intake of vitamin A, vitamin C, and vegetables were observed at
      week 24. In mononuclear-cell phospholipids, linoleic acid (18:2omega 6), which
      was significantly lower in patients than in controls at week 0, was increased at
      week 24. In contrast, arachidonic acid was decreased. Plasma prostaglandin E2
      levels were significantly lower in patients than in controls at week 0 and
      increased at week 24. The mononuclear-cell response for phytohemagglutinin
      correlated with 18:2omega 6 in mononuclear-cell phospholipids (r = 0.692, P <
      0.01). Improvement of the serum alanine-aminotransferase level correlated with an
      increase in the plasma alpha-tocopherol level (r = -0.667, P < 0.01) and
      increases in consumption of vitamin A, omega 3 polyunsaturated fatty acids, and
      vegetables. These findings suggest that a hypoenergetic diet rich in omega 3
      polyunsaturated fatty acids and antioxidants might be beneficial for obese
      patients with fatty liver.

PMID- 11448572
TI  - Malnutrition, nutritional indices, and early enteral feeding in critically ill
      children.
AB  - We measured the incidences of protein and fat depletions and the frequencies of
      acute and chronic protein-energy malnutrition during stress states in children
      and investigated the influence of early enteral feeding on nutrition indices and
      acute-phase proteins. Seventy-one, consecutively enrolled, critically ill
      children received early enteral feeding (energy intakes equal to 0.50, 1, 1.25,
      1.5, and 1.5 of the predicted basal metabolic rates on days 1 through 5,
      respectively) through nasogastric tubes. On the first day of the study, 16.7% of
      the patients already were depleted of protein and 31% of fat stores. Overall,
      16.9% were at risk for chronic protein-energy malnutrition and 21.1% for acute
      protein-energy malnutrition, whereas 4.2% and 5.6% already had chronic and acute,
      respectively protein-energy malnutrition. Only 22.7% of patients without protein
      deficiencies versus 37% of those at risk or already deficient developed multiple
      organ system failure. Transferrin and prealbumin levels improved at the end of
      the period of early enteral feeding (187 +/- 6.6 versus 233 +/- 7 mg/dL, P <
      0.0001; 15.1 +/- 2 versus 21.9 +/- 2.9 mg/dL, P < 0.0001; respectively);
      survivors had higher prealbumin levels than non-survivors (22.3 versus 15.5
      mg/dL). With logistic regression analysis, only repleted energy, not
      anthropometric or nutrition indices, was independently associated with survival
      (P = 0.05). These results reinforce the observation that critically ill children
      are at risk for fat or protein depletion and development of malnutrition, which
      is associated with increased morbidity and mortality. We conclude that early
      enteral nutrition improves nutrition indices and outcomes.

PMID- 11448573
TI  - Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body
      mass and muscle strength during a weight-training program.
AB  - We investigated whether creatine (CR) and beta-hydroxy-beta-methylbutyrate (HMB)
      act by similar or different mechanisms to increase lean body mass (LBM) and
      strength in humans undergoing progressive resistance-exercise training. In this
      double-blind, 3-wk study, subjects (n = 40) were randomized to placebo (PL; n =
      10), CR (20.0 g of CR/d for 7 d followed by 10.0 g of CR/d for 14 d; n = 11), HMB
      (3.0 g of HMB/d; n = 9), or CR-and-HMB (CR/HMB; n = 10) treatment groups. Over 3
      wk, all subjects gained LBM, which was assessed by bioelectrical impedance
      analysis. The CR, HMB and CR/HMB groups gained 0.92, 0.39, and 1.54 kg of LBM,
      respectively, over the placebo group, with a significant effect with CR
      supplementation (main effect P = 0.05) and a trend with HMB supplementation (main
      effect P = 0.08). These effects were additive because there was no interaction
      between CR and HMB (CR x HMB main effect P = 0.73). Across all exercises, HMB,
      CR, and CR/HMB supplementation caused accumulative strength increases of 37.5,
      39.1, and 51.9 kg, respectively, above the placebo group. The exercise-induced
      rise in serum creatine phosphokinase was markedly suppressed with HMB
      supplementation (main effect P = 0.01). However, CR supplementation antagonized
      the HMB effects on serum creatine phosphokinase (CR x HMB interactive effect P =
      0.04). Urine urea nitrogen and plasma urea were not affected by CR
      supplementation, but both decreased with HMB supplementation (HMB effect P <
      0.05), suggesting a nitrogen-sparing effect. In summary, CR and HMB can increase
      LBM and strength, and the effects are additive. Although not definitive, these
      results suggest that CR and HMB act by different mechanisms.

PMID- 11448574
TI  - Relation of vitamin A and carotenoid status to growth failure and mortality among
      Ugandan infants with human immunodeficiency virus.
AB  - Although growth failure is common during pediatric infection with human
      immunodeficiency virus (HIV) and associated with increased mortality, the
      relation of specific nutrition factors with growth and mortality has not been
      well characterized. A longitudinal study was conducted with 194 HIV-infected
      infants in Kampala, Uganda. Plasma vitamin A, carotenoids (alpha-carotene, beta
      carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin), and vitamin E
      were measured at age 14 wk, and weight and height were followed up to age 12 mo.
      Vitamin A and low plasma carotenoid concentrations were predictive of decreased
      weight and height velocity. Between ages 14 wk and 12 mo, 32% of infants died.
      Underweight, stunting, and low concentrations of plasma carotenoids were
      associated with increased risk of death in univariate analyses. Plasma vitamin A
      concentrations were not associated with risk of death. In a final multivariate
      model adjusting for weight-for-age, plasma beta-carotene was significantly
      associated with increased mortality (odds ratio: 3.16, 95% confidence interval:
      1.38 to 7.21, P < 0.006). These data suggest that low concentrations of plasma
      carotenoids are associated with increased risk of death during HIV infection
      among infants in Uganda.

PMID- 11448575
TI  - Hospital malnutrition: the Brazilian national survey (IBRANUTRI): a study of 4000
      patients.
AB  - OBJECTIVE: We assessed nutrition status and prevalence of malnutrition in
      hospital patients as determined by the Subjective Global Assessment Form,
      awareness of patients' nutrition status by health teams, and the use of nutrition
      therapy. METHODS: We enrolled 4000 hospital patients at least 18 y old who were
      covered by the Brazilian public health care system in a cross-sectional,
      multicenter epidemiologic study. We used Student's t and chi-square tests for
      univariate and multiple logistic regression analyses. RESULTS: Malnutrition was
      present in 48.1% of patients and severe malnutrition was present in 12.5% of
      patients. The prevalence of malnutrition was higher in the northern and
      northeastern regions of Brazil, where per-capita income is lower. Malnutrition
      correlated with primary diagnosis at admission, age (60 y), presence of cancer or
      infection, and longer hospital stay (P < 0.05). Fewer than 18.8% of patients'
      records contained information on nutrition-related issues. Nutrition therapy was
      used in 7.3% of patients (6.1% enteral nutrition and 1.2% parenteral nutrition).
      CONCLUSIONS: The prevalence of malnutrition in hospitalized patients in Brazil is
      high, physician awareness of malnutrition is low, and nutrition therapy is
      underprescribed.

PMID- 11448576
TI  - Predictors of survival in terminal-cancer patients with irreversible bowel
      obstruction receiving home parenteral nutrition.
AB  - Clinical, anthropometric, hematologic, and biochemical variables, evaluated
      immediately before starting nutritional treatment, were related to survival in 76
      terminal-cancer patients with irreversible bowel obstruction receiving home
      parenteral nutrition. At baseline, abnormally low values were observed in the
      following percentages of patients: 40.8% for body mass index, 59.2% for serum
      albumin, 84.2% for hemoglobin, 48.7% for lymphocyte count, and 60% for serum
      cholesterol. Survival on home parenteral nutrition ranged between 6 and 301 d,
      with a median of 74 d. Hemoglobin, serum albumin and serum cholesterol were lower
      in patients with a survival of less than 3 mo. With regard to Karnofsky
      performance status, median survival times were 63 d for a score below or equal to
      50 and 128 d for a score between 60 and 70. Albumin and a Karnofsky score above
      50 (but not age, weight, body mass index, lymphocyte count, or cholesterol)
      emerged (with a positive sign) as predictors of survival. In conclusion, terminal
      cancer patients with irreversible bowel obstruction are often malnourished,
      showing a high prevalence of anemia and hypoalbuminemia. Survival differs widely
      and can be predicted only to a limited extent from initial values of serum
      albumin and Karnofsky performance status.

PMID- 11448577
TI  - Reduction in energy expenditure after liver transplantation.
AB  - After successful liver transplantation (LTx), excessive weight gain is common
      among recipients. This rapid change in body morphology has been attributed to
      immunosuppressive regimens. The liver's role as a metabolic sensor and its
      autonomic innervation are pivotal in relaying humoral and neural information to
      the hypothalamus, where ingestive behavior is determined and has largely been
      ignored. We examined and assessed the contribution of drugs, energy intake, and
      energy expenditure on weight gain after LTx. Twenty-three patients were followed
      up at 3-mo intervals after LTx. Energy expenditure was measured by indirect
      calorimetry and dietary intake by diet diaries, and body composition was assessed
      with anthropometry and multifrequency bioelectrical impedance analysis.
      Cumulative drug doses were calculated, and associations between body composition
      and immunosuppressive regimens and energy expenditure were examined. Nine months
      after LTx, 20 of 23 (87%) recipients were overweight or obese, despite three
      fourths of this cohort being on weight-reduction regimens. After LTx, a decrease
      in measured energy expenditure was observed (60.3 +/- 1.6 kJ/kg of body cell mass
      pre-LTx versus 53.7 +/- 2.2 kJ/kg of body cell mass after 9 mo; P < 0.05).
      Multiple stepwise regression analysis showed that, when adjusted for body weight,
      the strongest predictor of fat mass at 9 mo after LTx was resting energy
      expenditure. Weight gain after LTx is not predicted by immunosuppressive drug
      dosage. The strong association between weight gain and energy economy might be a
      consequence of the loss of hepatic metabolic integration and accelerated further
      by increased energy intake. Effective management of weight gain will not be
      achieved until the mechanisms involved in altered energy homeostasis are
      elucidated.

PMID- 11448578
TI  - Insulin resistance in patients with cancer: relationships with tumor site, tumor
      stage, body-weight loss, acute-phase response, and energy expenditure.
AB  - We examined peripheral insulin sensitivity in 32 patients with cancer (17 with
      stomach cancer, 7 with colorectal cancer, and 8 with lung cancer) and 6 normal
      control subjects by the euglycemic hyperinsulinemic glucose clamp technique. The
      relationships between insulin resistance and tumor factors (type and stage),
      malnutrition, and inflammatory reaction were evaluated. Insulin sensitivity often
      was reduced in patients with cancer; however, the amount of glucose metabolized
      was not related to tumor site or stage. The decreased glucose uptake was
      negatively correlated with the acute-phase response but was not correlated with
      body-weight loss, serum albumin, or resting energy expenditure. Our results
      suggest that insulin resistance in cancer patients was not induced by
      malnutrition. Although the qualitative presence of tumor might be the major
      factor inducing insulin resistance, other factors such as inflammatory reactions
      might be involved in the development of insulin resistance.

PMID- 11448579
TI  - International perspectives: the profession of dietetics.
AB  - A survey about the professional characteristics of dietetics practice was mailed
      to 109 countries and representatives from 61 countries responded. Using the Human
      Development Index (HDI), a measure that reflects the life expectancy, education,
      and income of the population of each nation, countries were categorized as high,
      medium, or low HDI. This allowed comparisons among the HDI scores in the areas of
      education, professional practice, education, and practice competencies.
      Responding countries were 36.1% high HDI, 49.2% middle HDI, 8.2% low HDI, and
      6.6% were unclassified. Dietetics was a nationally recognized profession in 81%
      of countries, with most having a professional association that represented
      dietitians. Clinical dietetics was the most frequently selected area of practice,
      followed by food service. Undergraduate academic programs in dietetics were
      available in 79% of countries and 49% offered graduate degrees. Most respondents
      rated competencies in clinical and community nutrition, along with competencies
      in professional practice, as important to their work. The results of this study
      can serve as a baseline as the profession evolves. Leaders in the dietetics
      profession can use these results to identify areas that need improvement.
      Collaboration with the United Nations family and sources that fund global
      initiatives can help in providing resources for the advancement of the
      profession. When the effectiveness of dietitians is improved, favorable changes
      in nutritional well-being on the global level can be expected.

PMID- 11448580
TI  - Organ heavy-metal accumulation during parenteral nutrition is associated with
      pathologic abnormalities in rats.
AB  - OBJECTIVES: Metabolic bone disease, hepatic abnormalities, splenic insufficiency,
      and nephropathy have been associated with long-term total parenteral nutrition
      (TPN). We determined the heavy-metal contamination in TPN solutions and
      investigated whether it was associated with organ deposition and pathologic organ
      damage. METHODS: Five representative TPN solutions (two adult standard solutions,
      one renal solution, and one standard pediatric solution to reflect clinical
      practice) and 28 TPN components were analyzed with inductively coupled plasma
      mass spectrometry. Twenty-six male Fisher 344 rats were assigned to two groups
      (chow/NaCl = 8 and TPN = 18). TPN or NaCl was infused at a rate of 50 mL/d. After
      14 d, serum, femurs, spine, liver, kidneys, brain, spleen, and testes were
      analyzed for heavy-metal deposition by using inductively coupled plasma mass
      spectrometry. Tissues were fixed in formalin, sectioned, and stained with
      hematoxylin and eosin, periodic acid Schiff, and Masson's trichrome stain.
      Kidneys were fixed in gluteraldehyde for ultrastructural examination with
      scanning electron microscopy. RESULTS: The predominant sources of contaminants in
      TPN were amino acids (Al, As, Cr, Ge, Pb, Sn), dextrose (As, Ba, Cr, Sn), Ca
      gluconate (Al), K2PO4 (Al), lipid emulsion (As, Sn), and vitamins (As).
      Significant variations in the level of contamination depended on TPN formulation
      and brand of constituents. In the kidney, Pb, Cr, and Mn concentrations were
      greater than in controls, although there was no correlation with serum
      creatinine. Hepatic Cr and Pb concentrations were greater in TPN rats, although
      there was no correlation with serum aspartate aminotransferase or total
      bilirubin. Splenic Ba, Cr, Ge, Pb, Mn, and Sn concentrations were greater in TPN
      rats. Only serum Cr concentration was significantly correlated with splenic
      concentration (r = 0.46, P = 0.04). Brain and serum Ba concentrations were
      significantly correlated (r = 0.60, P = 0.007). No significant correlations were
      observed between any other metal in serum and that metal's respective organ
      concentration. No increase in heavy-metal accumulation was seen in the femur,
      spine, or testis. There were no significant depositions of As, Cd, Hg, St, or V
      in any of the organs examined. Serum Al and Cr concentrations were significantly
      increased in TPN rats, although there was no correlation with tissue
      concentrations. No significant increases in heavy-metal concentrations in tissue
      or plasma were observed for any of the other metals measurable by inductively
      coupled plasma mass spectrometry. Histologically in the TPN group, 50% of the
      rats had mild to moderate hepatic steatosis and 33% to 50% developed renal
      morphologic abnormalities; brains and spleens remained histologically normal.
      CONCLUSIONS: We found significant heavy-metal contamination of TPN solutions, and
      this contamination can lead to organ deposition and subsequent histologic
      abnormalities.

PMID- 11448581
TI  - Validation of dual x-ray absorptiometry for body-composition assessment of rats
      exposed to dietary stressors.
AB  - Evidence of the validity and accuracy of dual x-ray absorptiometry (DXA) to
      measure soft-tissue composition of laboratory rats with altered body composition
      associated with nutritional perturbations is lacking. We compared DXA
      determinations made in prone and supine positions with measurements of chemical
      composition of 49 male, weanling Sprague-Dawley rats that were fed the basal AIN
      93 growth diet, were fed the basal diet modified to contain 30% fat, were fasted
      for 2 d, were limit fed 6 g of the basal diet daily for 1 wk, or were treated
      with furosemide (10 mg/kg intraperitoneally 2 h before DXA). DXA produced similar
      estimates of body mass and soft-tissue composition in the prone and supine
      positions. DXA estimates of body composition were significantly correlated with
      reference composition values (R(2) = 0.371-0.999). DXA discriminated treatment
      effects on body mass, fat-free and bone-free mass, fat mass, and body fatness; it
      significantly underestimated body mass (1% to 2%) and fat-free and bone-free mass
      (3%) and significantly overestimated fat mass and body fatness (3% to 25%). The
      greatest errors occurred in treatment groups in which body mass was diminished
      and body hydration was decreased. These findings suggest that DXA can determine
      small changes in fat-free, bone-free mass in response to obesity and weight loss.
      Errors in DXA determination of fat mass and body fatness associated with extra
      corporeal fluid and dehydration indicate the need for revision of calculation
      algorithms for soft-tissue determination.

PMID- 11448582
TI  - Effect of thickening agents, based on soluble dietary fiber, on the availability
      of calcium, iron, and zinc from infant formulas.
AB  - Although it is accepted that dietary fiber probably is not needed in the diets of
      infants younger than 1 y, babies suffering from regurgitation are often fed with
      infant formulas thickened with considerable amounts of fiber. The effect of
      increasing amounts of alginic acid, locust-bean gum, and guar gum was studied
      from casein and whey-based infant formulas. A dialysis in vitro method with
      preliminary intraluminal digestion, adapted to the conditions of infants younger
      than 6 mo, was used. Human milk was used as the reference standard. Elemental
      contents of samples and dialysates were determined by atomic absorption
      spectrometry. Soluble dietary fiber inhibited mineral availability more in casein
      than in whey-based formulas. Mineral availabilities from casein- and whey-based
      formulas supplemented with 0.42 g of locust-bean gum/100 mL were 9.4% (0.7) and
      10.4% (0.6) for calcium (P < 0.05), 0.32% (0.08) and 1.45% (0.17) for iron (P <
      0.05), and 3.2% (0.2) and 5.6% (0.5) for zinc (P < 0.05), respectively. Calcium
      availability from the whey formula decreased in the presence of each fiber
      source, especially guar gum and alginic acid. Supplementing 2 g of alginic acid
      based agents per 100 mL depressed calcium availability from 13.3% (1.2) to 5.3%
      (0.3; P < 0.05). With respect to iron and zinc, availabilities increased from
      1.28% (0.28) to 6.05% (0.96; P < 0.05) and from 6.7% (0.6) to 10.2% (1.0),
      respectively, with the addition of 2 g of alginic acid (P < 0.05). Both gums
      lowered iron and zinc availabilities, and guar gum affected iron availability
      more severely than locust-bean gum did. Iron availabilities were 1.45% (0.17)
      from formula thickened with locust-bean gum (0.42 g/100 mL) and 0.92% (0.15) from
      formula thickened with guar gum (P < 0.05). Adding thickening agents based on
      soluble dietary fiber to traditional infant formulas probably affects calcium,
      iron, and zinc availability in various ways.

PMID- 11448583
TI  - Malondialdehyde modification of proteins in vitro is enhanced in the presence of
      acetaldehyde.
AB  - To test the hypothesis that the cardioprotective effect of alcohol is related to
      the inhibition of malondialdehyde (MDA) modification of proteins by acetaldehyde
      (AA), we studied the effect of AA on MDA modification of bovine serum albumin
      (BSA) in vitro. BSA was incubated simultaneously with a fixed concentration of
      MDA (70 mM) and different concentrations of AA (120, 60, 30, 10, or 0 mM) for 24
      h at 37 degrees C. The MDA-modified or AA-modified BSA was quantitated with
      immunoblotting by using specific anti-MDA and specific anti-AA protein antisera,
      respectively. In another set of experiments, BSA was incubated sequentially,
      first with different concentrations of AA and then with 70 mM of MDA. In both
      incubation protocols, the presence of AA and AA modification of BSA enhanced MDA
      binding. These in vitro observations suggest that the putative cardioprotective
      effects of alcohol or wine cannot be ascribed to AA-mediated reduction in MDA
      protein formation, a possible biochemical pathway of accelerated atherosclerosis.

PMID- 11448584
TI  - Effect of pentoxifylline on nitrogen balance and 3-methylhistidine excretion in
      parenterally fed endotoxemic rats.
AB  - Pentoxifylline interrupts early gene activation for tumor necrosis factor,
      interleukin-1, and interleukin-6 production and improves survival from
      experimental sepsis. These effects can alter nitrogen loss during critical
      illness. To determine the dose-dependent influence of pentoxifylline on nitrogen
      loss, 44 male Sprague-Dawley rats (220 to 265 g) were randomized to receive
      parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli
      026:B6 lipopolysaccharide (LPS) at 9 mg x kg(-1) x d(-1), or PN plus LPS plus a
      continuous infusion of pentoxifylline at either 25 (PEN25) or 100 mg x kg(-1) x
      d(-1) (PEN100) for 48 h. Before randomization, all animals underwent intravenous
      cannulation and 40 h of PN adaptation. All animals received isocaloric,
      isonitrogenous PN (160 kcal x kg(-1) x d(-1) and 1.0 gN x kg(-1) x d(-1)) and
      were kept nil per os except for water ad libitum. Administration of LPS
      significantly worsened nitrogen balance for all three groups compared with PN
      control; however, pentoxifylline only modestly improved nitrogen balance compared
      with LPS (206 +/- 255, -497 +/- 331, -332 +/- 329, and -310 +/- 383 mg/48hr for
      the PN, LPS, PEN25, and PEN100 groups, respectively; P < 0.001). Pentoxifylline
      did not significantly change 3-methylhistidine urinary excretion compared with
      LPS (573 +/- 180, 705 +/- 156, 780 +/- 326, and 683 +/- 266 microg/48 h for the
      PN, LPS, PEN25, and PEN100 groups, respectively, P not significant).
      Pentoxifylline, given in therapeutic doses after an endotoxin challenge,
      modestly, but not significantly, improved nitrogen balance. Urinary 3
      methylhistidine excretion was not influenced by pentoxifylline. A dose-dependent
      effect by pentoxifylline on these markers was not evident.

PMID- 11448585
TI  - Necessity of carnitine supplementation in semistarved rats fed a high-fat diet.
AB  - We investigated the effects of carnitine supplementation on lipid metabolism in
      semistarved rats. The semistarved rats were fed a high-fat diet and half the
      normal energy intake for 2 wk. Carnitine was supplied daily at a dose of 250
      mg/kg of body weight. The results showed that the concentration of plasma free
      carnitine increased significantly in semistarved and carnitine-supplemented rats
      compared with normal and semistarved rats. The activities of muscle carnitine
      palmitoyltransferase I and preheparin plasma lipoprotein lipase also were
      significantly increased in semistarved and carnitine-supplemented rats. The
      plasma triacylglycerol secretion rate was restored to normal by carnitine
      supplementation in semistarved rats. Urinary excretion of ketone bodies was
      reduced significantly after carnitine supplementation. We concluded that
      supplementation of carnitine can significantly increase the concentration of
      plasma free carnitine and improve lipid metabolism in semistarved rats fed a high
      fat diet.

PMID- 11448586
TI  - The importance of the refeeding syndrome.
AB  - In this review we discuss the refeeding syndrome. This potentially lethal
      condition can be defined as severe electrolyte and fluid shifts associated with
      metabolic abnormalities in malnourished patients undergoing refeeding, whether
      orally, enterally, or parenterally. It can be associated with significant
      morbidity and mortality. Clinical features are fluid-balance abnormalities,
      abnormal glucose metabolism, hypophosphatemia, hypomagnesemia, and hypokalemia.
      In addition, thiamine deficiency can occur. We describe which patient groups are
      more at risk for this syndrome and the clinical management of the condition.

PMID- 11448587
TI  - How does the body deal with energy from alcohol?

PMID- 11448588
TI  - Cow's milk protein allergy and possible means for its prevention.

PMID- 11448589
TI  - Folate and chemoprevention of colorectal cancer: Is 5-methyl-tetrahydrofolate an
      active antiproliferative agent in folate-treated colon-cancer cells?

PMID- 11448590
TI  - Increased plasma tryptophan in HIV-infected patients treated with pharmacologic
      doses of nicotinamide.
AB  - OBJECTIVE: Decreased plasma tryptophan in persons infected with human
      immunodeficiency virus (HIV) was first reported over a decade ago, and this
      observation has since been confirmed by many groups. Before this study, only
      zidovudine (an antiviral medication) had been reported to reverse plasma
      tryptophan depletion in HIV-infected persons. Starting with the hypothesis that
      HIV induces a pellagra-like state and that plasma tryptophan in HIV-infected
      patients is decreased as a known biochemical correlate of pellagra, we predicted
      that niacin therapy would reverse plasma tryptophan depletion as it does in
      pellagra. METHODS: After receiving approval from the institutional review board,
      we treated HIV-infected patients for 2 mo with high-dose niacin in the form of
      oral nicotinamide. RESULTS: There was an average 40% increase in plasma
      tryptophan (P = 0.01) in the four HIV-infected individuals who completed the 2-mo
      protocol. This finding was specific in that four other amino acids, which have
      been shown to have significant plasma concentration alterations during HIV
      infection (i.e., cystine, methionine, taurine, and lysine), showed no significant
      change with nicotinamide therapy. CONCLUSIONS: There were no adverse side effects
      attributable to this treatment. The effects of high-dose nicotinamide treatment
      on morbidity or mortality in HIV-infected persons are yet to be determined. This
      report marks the first successful use of a vitamin to reverse this HIV-induced
      metabolic abnormality.

PMID- 11448591
TI  - Lack of association between plasma leptin levels and appetite in children with
      iron deficiency.
AB  - A negative correlation between leptin and appetite or food intake has been shown
      in healthy individuals. However, the role of leptin in clinical conditions
      characterized by anorexia has not been established. One of the well-known
      clinical features of iron-deficiency anemia is poor appetite. We examined the
      changes in plasma leptin levels in relation to expected improvement in appetite
      with iron treatment in children with iron deficiency. In 24 infants and small
      children (mean age +/- standard deviation = 19.6 +/- 7.7 months) with iron
      deficiency, we studied plasma leptin levels before and after iron therapy. After
      15.0 +/- 2.4 wk of iron treatment, serum ferritin levels improved significantly,
      with accompanying increases in their subjective appetite scores and food intakes.
      However, as their mean age and plasma leptin levels adjusted their body mass
      indexes were unchanged. Serum ferritin correlated significantly with appetite
      score (r = 0.680, P < 0.001) and food intake (r = 0.480, P < 0.01). Leptin
      correlated only with body mass index (r = 0.405, P < 0.01). Lack of association
      between plasma leptin levels and degree of appetite in iron-deficient children
      treated with iron suggests a leptin-independent mechanism for the observed
      increase in appetite.

PMID- 11448592
TI  - Anorexia, sarcopenia, and aging.
AB  - Food intake declines throughout the life span. This physiologic anorexia of aging
      is caused in part by alterations of stomach-fundus compliance and release and
      activity of cholecystokinin. In addition, the decline in testosterone in males
      results in elevated leptin levels that increase the anorexia. There is also
      evidence that cytokines play a role in the pathogenesis of anorexia and
      sarcopenia, thus accelerating the development of frailty in older persons.
      Numerous treatable causes of anorexia and weight loss exist. Depression is the
      most commonly diagnosed cause of pathologic weight loss in older persons.

PMID- 11448593
TI  - How the immune and nervous systems interact during disease-associated anorexia.
AB  - Anorexia is one of the most common symptoms associated with illness and
      constitutes an adaptive strategy in fighting acute infectious diseases. However,
      prolonged reduction in food intake and an increase in metabolic rate, as seen in
      the anorexia-cachexia syndrome, lead to depletion of body fat and protein
      reserves, thus worsening the organism's condition. Because the central nervous
      system controls many aspects of food intake, soluble factors known as cytokines
      that are secreted by immune cells might act on the brain to induce anorexia
      during disease. This review focuses on the communication pathways from the immune
      system to the brain that might mediate anorexia during disease. The vagus nerve
      is a rapid route of communication from the immune system to the brain, as
      subdiaphragmatic vagotomy attenuates the decrease in food-motivated behavior and
      c-Fos expression in the central nervous system in response to peripheral
      administration of the proinflammatory cytokine, interleukin-1beta, or bacterial
      lipopolysaccharide. At later time points after peripheral lipopolysaccharide
      administration, interleukin-1 itself acts in the brain to mediate anorexia and is
      found in the arcuate nucleus of the hypothalamus. The mechanisms by which
      interleukin-1beta gains access to the brain and the potential role of
      neuropeptide-Y-containing neurons in the arcuate hypothalamus in mediating
      anorexia during disease are discussed.

PMID- 11448594
TI  - Modulation of human immune and inflammatory responses by dietary fatty acids.
AB  - I review the effects of the amount and composition of dietary fat on indices of
      human immune and inflammatory responses. A reduction in the amount of fat intake
      enhanced several indices of immune response, including lymphocyte proliferation,
      natural-killer-cell activity, cytokine production, and delayed-type
      hypersensitivity. When total fat intake was held constant, an increase in the
      intake of linoleic acid (18:2 omega-6) or arachidonic acid (20:4 omega-6) by
      healthy human volunteers did not inhibit many indices of immune response tested
      but did increase the production of inflammatory eicosanoids (prostaglandin E2 and
      leukotriene B4). Supplementation of human diets with omega-3 fatty acids reduced
      several aspects of neutrophil, monocyte, and lymphocyte functions, including the
      production of inflammatory mediators. Most of the studies have indicated
      reductions in these functions, with a minimum of 1.2 g/d of supplementation with
      eicosapentaenoic acid and docosahexaenoic acid for 6 wk. However, other studies
      concomitantly supplementing with 205 mg/d of vitamin E did not find inhibition of
      immune-cell functions, even with larger amounts and longer durations of
      supplementation with these fatty acids. One study reported that supplementation
      with docosahexaenoic acid selectively inhibits inflammatory responses without
      inhibiting T- and B-cell functions. Despite some discrepancies, fish oils have
      been used successfully in the management of several inflammatory and autoimmune
      diseases. The potential for the use of fish oils in the management of these
      diseases is tremendous, even though further studies are needed to establish safe
      and adequate intake levels of omega-3 fatty acids.

PMID- 11448595
TI  - Defining mechanisms of omega-3 fatty-acid activity.

PMID- 11448596
TI  - Body composition distribution with age--growth charts for adults?

PMID- 11448597
TI  - The patient with incurable aphagic cancer: to feed or not to feed?

PMID- 11448598
TI  - How does the body deal with energy from alcohol?

PMID- 11448599
TI  - Dual-energy X-ray absorptiometry for the measurement of body composition in small
      laboratory animals.

PMID- 11448600
TI  - Magnesium and bone strength.

PMID- 11448601
TI  - TPN or intravenous food poisoning?

PMID- 11448602
TI  - Changing infant-feeding practices and growth in Tunisian children.

PMID- 11448603
TI  - Organic-metal toxicity and total parenteral nutrition.

PMID- 11448604
TI  - Intracellular energy signals and dietary calcium: a milky way to the physiologic
      control of hyperphagia and obesity?

PMID- 11448605
TI  - Discovery of human zinc deficiency: impact on human health.

PMID- 11448606
TI  - Role of essential amino acids in renal failure.

PMID- 11448607
TI  - Manganese intoxication and parenteral nutrition.

PMID- 11448608
TI  - Assessing body composition in athletes.

PMID- 11448609
TI  - Glutathione--nutritional and pharmacological viewpoints: Part III.

PMID- 11448610
TI  - Nutrition support and cancer.

PMID- 11448612
TI  - Letter from the editor.

PMID- 11448613
TI  - Linoleic acid partially restores the triglyceride content of conjugated linoleic
      acid-treated cultures of 3T3-L1 preadipocytes.
AB  - We have previously demonstrated that a crude mixture of commercially available
      conjugated linoleic acid (CLA) isomers suppressed triglyceride (TG) content and
      induced apoptosis in post-confluent cultures of murine 3T3-L1 preadipocytes.
      Furthermore, we found that 100 &mgr;M of trans-10, cis-12 isomer of CLA had a
      greater TG-lowering and apoptotic effect than the crude mixture of CLA isomers.
      Therefore, the purpose of this study was to: 1) compare the potencies of the two
      main isomers found in the crude mixture of CLA isomers, e.g. cis-9, trans-11
      (41%) and trans-10, cis-12 (44%); and 2) determine if the TG-reducing actions of
      CLA could be attenuated by the addition of increasing levels of linoleic acid to
      the cultures. Preadipocyte differentiation was assessed on day 7 of the
      differentiation protocol by measuring TG content (per 10(6) cells), cell size,
      and lipid staining. In experiment 1, post-confluent cultures of 3T3-L1
      preadipocytes treated for the first 6 d of differentiation with 100 &mgr;M of a
      crude mixture of CLA isomers or 44 &mgr;M of trans-10, cis-12 CLA had less TG
      content than all other cultures. In contrast, cultures supplemented with 41
      &mgr;M of the cis-9, trans-11 CLA isomer had the same amount of TG as the BSA
      controls. In experiment 2, post-confluent cultures of 3T3-L1 preadipocytes
      treated for the first 6 d of differentiation with 50 &mgr;M trans-10, cis-12 CLA
      had less TG content and a greater number of smaller cells (10-12.5 microns)
      compared to all other treatments. CLA-treated cultures supplemented with
      increasing levels of linoleic acid (50-200 &mgr;M) had greater TG contents and
      greater numbers of larger cells (15-20 microns) than cultures treated with 50
      &mgr;M of the trans-10, cis-12 CLA isomer alone. These data demonstrate that: 1)
      the TG-lowering effects of the crude mixture of CLA isomers is due almost
      exclusively to the trans-10, cis-12 isomer; and 2) linoleic acid partially
      reverses CLA's attenuation of TG content, suggesting that these unsaturated fatty
      acids may compete for incorporation into TG or phospholipid-derived eicosanoids
      that regulate preadipocyte differentiation.

PMID- 11448614
TI  - Effects of multinutrient supplementation on antioxidant defense systems in
      healthy human beings.
AB  - Oxidative damage involved in the pathogenesis of many diseases, such as
      cardiovascular disease, cancer and diabetics. The antioxidant defense system
      plays an important role in protecting body from oxidative damage. Numerous
      studies have been shown that a single vitamin or mineral supplementation has the
      beneficial effect on the antioxidant defense system. However, the overall
      combined effect of multinutrient supplementation on antioxidant defense system
      remains to be clarified. In the present double blind, placebo-controlled study,
      the antioxidative defense system was measured in 34 healthy subjects before and
      after multinutrient supplementation. Plasma vitamin C, E and beta-carotene,
      erythrocyte vitamin E, as well as whole blood selenium all showed increase at 5
      weeks of supplementation. The activities of catalase (CAT) and glutathione
      peroxidase (GPX), but not superoxide dismutase (SOD), as well as GSH level were
      significantly increased at 16 weeks of supplementation. Moreover, the resistance
      of erythrocytes to 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH)-induced
      oxidation was elevated at 5 weeks after supplementation. These results clearly
      demonstrated that short-term supplementation (16 weeks) with multinutrient could
      markedly improve antioxidative vitamin status and enzymatic activities. These
      improvements also led to the reduction of RBC susceptibility to free radial
      peroxidation.

PMID- 11448615
TI  - Effect of sucrose addition to drinking water, that induces hypertension in the
      rats, on liver microsomal Delta9 and Delta5-desaturase activities.
AB  - This study was undertaken with the aim of investigating the effect of sucrose
      addition to the drinking water of rats who were fed with the same diet as a
      control group, on Delta9- and Delta5-desaturase activities and on the fatty acid
      composition of serum and liver microsomes. Weanling male Wistar rats had 30%
      sucrose in their drinking water for 20 weeks. An increase in total calories
      consumed, visceral fat accumulation, insulin, triglycerides and blood pressure
      and a decrease in the food intake were observed in the sucrose-fed group as
      compared with the control group. A decrease in linoleic and alpha-linolenic acid
      (essential fatty acids) in all serum lipid fractions of sucrose-fed rats was
      found. This observation correlated with a low food intake by sucrose-fed rats.
      The conversion of [1 (14)C]-palmitic to [1 (14)C]-palmitoleic acid by Delta9
      desaturase activity was increased in sucrose-fed compared with control rats,
      while the conversion of [1 (14)C]-dihomo-gamma-linolenic acids by Delta5
      desaturase activity was depressed. In sucrose-fed as compared to control rats,
      the proportion of palmitoleic and oleic fatty acids was increased. Arachidonic
      acid was decreased in sucrose-fed rats. The 1,6-diphenylhexatriene fluorescence
      polarization of the microsomal membranes was significantly lower in the sucrose
      fed group compared to the control group. These results indicate that the sucrose
      addition to the drinking water of the rats increased microsomal Delta9-desaturase
      activity and membrane disorder and decreased the activity of the Delta5
      desaturase, a key enzyme in the biosynthesis of arachidonic acid, implicated in
      hypertension.

PMID- 11448616
TI  - A review of latest research findings on the health promotion properties of tea.
AB  - Important progress has been made in the past five years concerning the effects of
      green and black tea on health. Experimentation with new accurate tools provide
      useful information about the metabolism of tea components in the body, their mode
      of action as antioxidants at the cellular level and their protective role in the
      development of cancer, cardiovascular disease and other pathologies. The use of
      tea components as nutraceuticals and functional foods are also discussed.

PMID- 11448617
TI  - Fatty acid oxidation and fatty acid synthesis in energy restricted rats(1).
AB  - The importance of fat oxidation and fatty acid synthesis were examined in rats
      fed approximately one half their ad libitum food intake for a period of 13 days
      followed by 7 days of ad libitum feeding (refed rats). This study was undertaken
      because previous reports demonstrated that refed rats rapidly accumulated body
      fat. Our results confirmed this observation: refed rats accrued body fat and body
      weight at rates that were approximately 3 times higher than controls. Evidence
      for a period of increased metabolic efficiency was demonstrated by measuring the
      net energy requirement for maintenance over the refeeding period: refed rats had
      a reduced metabolic rate during the period of energy restriction (approximately
      30% lower than control) and this persisted up to 2 days after the reintroduction
      of ad libitum feeding. The major factor responsible for the rapid fat gain was a
      depressed rate of fatty acid oxidation. Calculations of protein and carbohydrate
      intake over the refeeding period showed that the simplest explanation for the
      decrease in fatty acid oxidation is fat sparing. This is possible because of the
      large increase in dietary carbohydrate and protein intake during the refeeding
      period when metabolic rates are still depressed. The increased carbohydrate and
      protein may adequately compensate for the increasing energy requirements of the
      ER rats over the refeeding period affording rats the luxury of storing the excess
      dietary fat energy.

PMID- 11448618
TI  - Gender related differences in the effect of aging on blood amino acid
      compartmentation*
AB  - This work has been focused on the study of the variations in blood amino acid
      compartmentation (plasma and blood cells) with aging, both in men and women.
      Aging is a situation which, under the influence of gender, involves a decline in
      body weight functions and variations in energy metabolism with a deterioration of
      muscular metabolism leading to changes in amino acid handling. We determined the
      blood levels of individual amino acids in whole blood, plasma compartment and
      blood cell compartment of 51 men and 51 women. Subjects were classified in three
      age groups-AG1 (18 to 35 y), AG2 (35-50 y) and AG3 (more than 50 y). Aging was
      accompanied by significant changes in blood levels of amino acids showing gender
      linked differences which were distinct for both blood compartments (plasma and
      blood cells). In men, aging was accompanied by a drop in blood levels of several
      amino acids, due mainly to the plasma compartment, whereas in women aging brought
      about a rise in blood levels of various amino acids mainly in blood cell
      compartment. This paper contributes to enhancing the physiological importance of
      the blood cell pool in the handling of amino acids.

PMID- 11448622
TI  - Axis determination in C. elegans: initiating and transducing polarity.
AB  - The anterior-posterior axis in Caenorhabditis elegans is determined by the sperm
      and leads to the asymmetric localisation of PAR (partitioning-defective)
      proteins, which are critical for polarity. New findings demonstrate that sperm
      asters play a critical role and suggest models for how PAR asymmetry is
      established. In addition, studies of blastomere fate determination and
      heterotrimeric G proteins have started to uncover how initial polarity may be
      translated into the asymmetric distribution of maternal proteins and the control
      of spindle position.

PMID- 11448623
TI  - Axis formation during Drosophila oogenesis.
AB  - Recent advances shed light on the cellular processes that cooperate during
      oogenesis to produce a fully patterned egg, containing all the maternal
      information required for embryonic development. Progress has been made in
      defining the early steps in oocyte specification and it has been shown that
      progression of oogenesis is controlled by a meiotic checkpoint and requires
      active maintenance of the oocyte cell fate. The function of Gurken signalling in
      patterning the dorsal-ventral axis later in oogenesis is better understood.
      Anterior-posterior patterning of the embryo requires activities of bicoid and
      oskar mRNAs, localised within the oocyte. A microtubule motor, Kinesin, is
      directly implicated in localisation of oskar mRNA to the posterior pole of the
      oocyte.

PMID- 11448624
TI  - From fertilization to gastrulation: axis formation in the mouse embryo.
AB  - Although much remains unknown about how the embryonic axis is laid down in the
      mouse, it is now clear that reciprocal interactions between the extraembryonic
      and embryonic lineages establish and reinforce patterning of the embryo. At early
      post-implantation stages, the extraembryonic ectoderm appears to impart proximal
      posterior identity to the adjacent proximal epiblast, whereas the distal visceral
      endoderm signals to the underlying epiblast to restrict posterior identity as it
      moves anteriorward. At gastrulation, the visceral endoderm is necessary for
      specifying anterior primitive streak derivatives, which, in turn, pattern the
      anterior epiblast. Polarity of these extraembryonic tissues can be traced back to
      the blastocyst stage, where asymmetry has been linked to the point of sperm entry
      at fertilization.

PMID- 11448625
TI  - Axis formation and patterning in zebrafish.
AB  - A large collection of mutations affecting zebrafish embryogenesis was described
      in 1996. The cloning of the affected genes has now provided novel insights into
      the role and regulation of signaling by BMP, Nodal, Wnt, FGF, Hedgehog, Delta,
      Slit, retinoic acid and lipids. Detailed analyses have revealed a complex genetic
      network that patterns the early embryo.

PMID- 11448626
TI  - Axis formation and polarity in plants.
AB  - We have recently gained insight into a number of mechanisms governing the
      formation of the major axes that define the embryonic and adult plant body plan.
      Phenotypic analysis and molecular characterization of mutants with aberrant
      morphogenesis has led to a better understanding of key processes including the
      generation of the shape of the apical embryo, the establishment and maintenance
      of the radial pattern of the root, and the placement of lateral organ primordia
      around the shoot apical meristem.

PMID- 11448627
TI  - Stem cell fate and patterning in mammalian epidermis.
AB  - Recent studies highlight characteristics of epidermal stem cells that were not
      fully appreciated before. Stem cells are multipotential and signals exchanged
      with their neighbours help to regulate exit from the stem cell compartment and
      differentiation along specific lineages. Stem cells exhibit a high degree of
      spatial organisation, and cell clustering and motility contribute to the assembly
      and maintenance of the epidermis.

PMID- 11448628
TI  - Lineage diversity in the Drosophila nervous system.
AB  - The detailed descriptions of cellular lineages in the Drosophila nervous system
      have provided the foundations for an in-depth genetic analysis of the mechanisms
      that regulate fate decisions at every cell cycle.

PMID- 11448629
TI  - Cell lineage, cell signaling and the control of plant morphogenesis.
AB  - It is clear that cell-cell signaling is critical for the development of both root
      and shoot structures. Recently, several of the key gene products required for
      intercellular signaling have been defined, and the developmental processes
      regulated by cell-cell interactions are beginning to be elucidated. Surprisingly,
      these results suggest that the mechanisms by which plant cells communicate with
      each other may be quite distinct from those used in animal systems.

PMID- 11448630
TI  - Invertebrate myogenesis: looking back to the future of muscle development.
AB  - Recent studies in invertebrates have provided important mechanistic insights into
      several general aspects of muscle development. Two new genes have been identified
      that are involved in muscle fusion in Drosophila and a novel maternal component
      was shown to be responsible for myogenic determination in an ascidian. In
      addition, genetic analyses of nematode and Drosophila homologues of factors known
      to be myogenic regulators in other species yielded surprising findings about both
      the evolutionary conservation and divergence of these functions. Drosophila
      myogenesis has become a highly informative model for understanding the interplay
      between the signaling and transcriptional networks that underlie cell-fate
      specification during embryonic development.

PMID- 11448631
TI  - Skeletal muscle formation in vertebrates.
AB  - Research in the past year has added to our understanding of the signalling
      systems that specify myogenic identity in the embryo and of the regulation and
      roles of MyoD family members. New insights into the movement of muscle precursor
      cells include the demonstration that Lbx1 is essential for their migration from
      the somite to some but not all sites of muscle formation elsewhere. Later in
      development, ras as well as calcineurin signalling is now implicated in the
      definition of slow versus fast fibre types. The myogenic identity of precursor
      cells in the adult depends on Pax7, the orthologue of Pax3 which is required for
      early myogenesis; this finding is of major importance for muscle regeneration and
      the active field of stem cell research.

PMID- 11448632
TI  - Turning floral organs into leaves, leaves into floral organs.
AB  - The development of the floral organs is specified by the combinations of three
      classes of gene for organ identity in the 'ABC' model. Recently, molecular
      genetic studies have shown this model is applicable to grass plants as well as
      most eudicots. Transcription factor complexes of ABC and homologous proteins form
      the molecular basis of the ABC model.

PMID- 11448633
TI  - Cell migration in invertebrates: clues from border and distal tip cells.
AB  - Recent studies in two invertebrate systems, border cells in Drosophila
      melanogaster and distal tip cells in Caenorhabditis elegans, have provided
      important insight into the mechanisms of directed cell migration. These migrating
      cells are guided by extracellular signals, such as EGF, TGF-beta and netrin. In
      addition, metalloproteases alter the extracellular matrix of the tissue through
      which these cells migrate. Along the migratory path, migrating cells respond to
      changes in guidance signals by altering the expression of receptor signaling
      pathways. Finally, Dock180, CrkII and the GTPase Rac link the extracellular
      signals to the cellular machinery that controls cell motility.

PMID- 11448634
TI  - Cell movements during vertebrate development: integrated tissue behaviour versus
      individual cell migration.
AB  - Cell migration during development is fundamental to the establishment of the
      embryonic architecture. Depending on the context, cells may move either as
      integrated sheets of tissue or individually. Recently, molecules that are
      involved in both these types of cell behaviour have been identified, helping us
      to understand developmental processes as important as gastrulation and neural
      crest formation, and ultimately, the morphogenetic movements that shape the
      embryo.

PMID- 11448635
TI  - Wing disc development in the fly: the early stages.
AB  - The establishment of the wing anlage in Drosophila is dependent on the presence
      of two organizing centers located at the boundaries of the dorsoventral and
      anteroposterior compartments. How these boundaries are defined was not understood
      until recently. Furthermore, nothing was known about how the hinge region of the
      wing is defined. Recent data have now started to provide some insight in the
      molecular processes required for the definition of the major boundaries and
      subdivision of the wing anlage into the hinge and blade region.

PMID- 11448636
TI  - Vertebrate limb development--the early stages in chick and mouse.
AB  - More news this year about FGFs and their roles in vertebrate limb initiation; Wnt
      signalling is shown for the first time to be another component of the signalling
      cascade involved in early limb formation. Ectodermal compartments that control
      apical ridge formation were previously described in chick embryos and are now
      shown to exist in mouse embryos; Engrailed1 is expressed in the ventral
      ectodermal compartment but experiments in both chick and mouse show that it is
      not responsible for compartment specification.

PMID- 11448637
TI  - Micronuclei induction, cell cycle delay and apoptosis as markers of cellular
      stress caused by ursodeoxycholic acid in human lymphocytes.
AB  - Ursodeoxycholic acid (UDCA) is a bile acid (BA) used for cholesterol gallstone
      dissolution. Since epidemiological evidence indicates that BAs can be involved in
      the etiology of colorectal cancer, we investigated the effects of UDCA and its
      physiologically produced taurine conjugate tauroursodeoxycholic acid (TUDCA) on
      human lymphocyte cultures in terms of genetic damage in the form of micronuclei
      (MN) production, cell cycle modifications and induction of apoptosis. With
      respect to controls, treatment with UDCA (from 10 microg/ml) caused a dose
      related increase in MN, whereas TUDCA caused no significant increase (up to 1000
      microg/ml). Fluorescence in situ hybridization (FISH) analysis using
      pancentromeric probes suggested that UDCA exerts aneugenic activity.
      Bromodeoxyuridine/Hoechst flow cytometry showed that both BA significantly
      inhibit cell cycle progression (UDCA at 100 microg/ml, and TUDCA, more markedly
      at 300-1000 microg/ml). Neither UDCA nor TUDCA affected induction of apoptosis,
      as evaluated by the Annexin-V-Fluos assay. We conclude that UDCA is potentially
      genotoxic. However, taking into account the characteristics of other
      physiological BA, our findings are in line with the concept that long-term UDCA
      treatment may be safely administered. The multi-assay approach reported here
      could be useful in the toxicological evaluation of newly developed BA analogs as
      candidates for pharmacological use.

PMID- 11448638
TI  - The application of spectral karyotyping (SKY) and fluorescent in situ
      hybridization (FISH) technology to determine the chromosomal content(s) of
      micronuclei.
AB  - DNA loss by the process of micronucleation is associated with aging, cancer and
      environmental exposure. The primary aim of this study was to identify the
      chromosomal origin of the DNA excluded into micronuclei (MN). This was achieved
      using a novel application of SKY and FISH technologies. Cytochalasin B (Cyt B)
      treated lymphocyte cultures from three females (aged 28, 42 and 72) were
      analyzed. SKY revealed that the majority of MN (89.8, 82.9, and 97.6% in the 28-,
      42- and 72-year-old (y.o.), respectively) had a uniform, single color, suggesting
      that they were comprised of DNA from a single chromosome. Using a pancentromeric
      probe, most of the MN (82% in 28 y.o., 69% in 42 y.o. and 80% in 72 y.o.) had one
      centromere signal present. Overall, the confirmation studies (using FISH with
      chromosome-specific WCP) were in agreement with the SKY chromosomal assignments
      for 71.1% of the MN. Although the SKY analysis showed that all of the 23
      chromosomes (22 autosomes and the X chromosome) could be present in the MN,
      overall, the X chromosome was seen most frequently. DNA from the X chromosome was
      seen in 50.6% of MN in the 42 y.o. individual, whereas in the 28 and 72 y.o. it
      was seen in 12.2 and 7.1% of MN, respectively. This difference (P<0.0001) in the
      frequencies of X chromosome exclusion into MN among individuals was independently
      confirmed using a single whole chromosome painting probe (WCP) for the X
      chromosome. SKY also showed variation in the frequency of autosomal exclusion
      into MN between chromosomes and between females. Collectively, this study
      supports the hypothesis that the majority of MN contain DNA from a single,
      monocentric chromosome. The use of SKY technology for the identification of the
      chromosomal content(s) of MN provides an opportunity for expansion of our
      knowledge of the chromosomal changes that accompany MN formation.

PMID- 11448639
TI  - Increased levels of comet-detected spermatozoa DNA damage following in vivo
      isotopic- or X-irradiation of spermatogonia.
AB  - To investigate whether DNA damage arising in spermatogenic germ cells can be
      detected in resultant sperm, we have irradiated murine testis and collected
      spermatozoa from the vas deferens 45 days later. These cells were derived from
      spermatogonia present at the time of irradiation. Two forms of irradiation were
      used, external X-rays (4Gy) and internal auger electrons from contamination of
      the male mouse with the isotope Indium-114m (1.85MBq), which was localised in the
      testis. Both forms of irradiation produced a profound fall in vas deferens sperm
      count and testis weight, Indium-114m being more effective. Using the neutral
      Comet assay for double strand break detection, significant increases in sperm
      comet tail length and moment were observed. The levels of damage were similar for
      both treatments. Care had to be taken during the assay to distinguish between
      sperm and somatic cells as the proportion of the latter increased after
      irradiation. We conclude that the comet assay can detect DNA damage in
      spermatozoa after the in vivo exposure of male germ cells to a known testicular
      genotoxic agent. The assay may be useful for the assessment of sperm DNA damage
      (double stranded) associated with male infertility and post-fertilization
      developmental abnormalities in the offspring.

PMID- 11448640
TI  - High incidence of mosaic mutations induced by irradiating paternal germ cells of
      the medaka fish, Oryzias latipes.
AB  - Delayed-type mutations induced by radiation have recently been demonstrated in
      various somatic-cell systems. Such mutations are thought to result from the
      transmission of genetic instability through many cell divisions subsequent to a
      single exposure to ionizing radiation. Here, we have examined whether
      'transgenerational' delayed-type mutations can arise during embryonic development
      of the medaka fish as a result of exposing the sperm and spermatids of live fish
      to 137Cs gamma-radiation. To do this, we made use of a sensitive specific-locus
      test (SLT) for the medaka that we have recently developed. Because the medaka has
      a transparent egg membrane and embryo body, both visible mosaics and whole-body
      mutations can be detected during development at an early-expressed pigmentation
      locus. When wild-type +/+ males were gamma-irradiated and then mated with wl/wl
      females, the frequency of F1 embryos with both wild-type orange leucophores
      (wl/+) and mutant-type white leucophores (wl/wl*) (mosaic mutants) was about
      5.7x10(-3)/Gy. The frequency of embryos with only white leucophores (whole-body
      mutants) was about 1.3x10(-3)/Gy. These results suggest that delayed mutations
      frequently arise in medaka fish embryos that have been fertilized with irradiated
      sperm. Some possible mechanisms involved in the generation of these delayed
      mutational events (including genomic instability in the early embryos) are
      discussed.

PMID- 11448641
TI  - Micronucleus induction in Syrian hamster embryo cells following exposure to 50 Hz
      magnetic fields, benzo(a)pyrene, and TPA in vitro.
AB  - Electromagnetic fields (EMFs) have been associated with increased incidence of
      cancer suggested by epidemiological studies. To test the carcinogenic potency of
      EMF, the in vitro micronucleus assay with SHE cells has been used as a screening
      method for genotoxicity. A 50Hz magnetic field (MF) of 1mT field strength was
      applied either alone or with the tumour initiator benzo(a)pyrene (BP) or the
      tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). All three treatments
      were applied in single, double or triple treatment regimes. MF or TPA (1nM) alone
      did not affect the number of micronuclei (MN) in initiated and non-initiated SHE
      cells. Changing the schedule of the typical initiation protocol, namely applying
      the initiator (BP) during exposure to MF, results in an 1.8-fold increased MN
      formation compared to BP treatment alone. Combined experiment with BP, TPA and MF
      did not cause further MN formation. Since initiation during MF exposure caused a
      significant increased MN formation, our findings suggest that MFs enhance the
      initiation process of BP. We think that this MF-enhanced co-carcinogenic effect
      is caused by an indirect "cell activation" process. The resulting genomic
      instability is proposed to be due to free radicals and/or to the unscheduled
      "switching-on" of signal transduction pathways.

PMID- 11448642
TI  - Kinetics of micronucleus induction and cytotoxic activity of colchicine in murine
      erythroblast in vivo.
AB  - In previous studies, we inferred some pharmacokinetic and pharmacodynamic
      parameters of alkylating agents and antimetabolites by comparing their kinetics
      of micronucleated polychromatic erythrocyte (MN-PCE) induction with the one
      obtained after the exposure to gamma rays in peripheral blood of mice, assuming
      that radiation acts immediately because it does not require absorption and
      distribution in the organism. According to our earlier studies, the kinetics of
      MN-PCE induction depends mainly on the following: (i) the cytotoxic effects that
      in turn could affect the duration of cell division; (ii) the pharmacokinetics
      including the metabolic activation requirement; and (iii) the mechanism of MN
      induction. The aim of the present study was to analyze the kinetics of MN-PCE
      induction by an aneuploidogen that induces micronuclei by acting on the
      achromatic spindle. The kinetics of MN-PCE induction by colchicine, as well as
      the reduction in the PCE frequency over time was determined in peripheral blood
      of mice treated with different doses of the aneuploidogen. The genotoxic effect,
      established as the area beneath the curve (ABC) of MN-PCE versus time-response,
      indicates an almost directly proportional relationship with respect to dose.
      Similarly, the relationship between dose and cytotoxic effect determined as the
      ABC of PCE versus time was inversely proportional, suggesting a relationship
      between both endpoints and doses administered. However, the number of cells
      affected by these two phenomena indicates that cytotoxicity is not necessarily
      caused, or at least not only by genotoxicity. The analysis of the kinetics of MN
      PCE induction after the treatment with non-cytotoxic dose of colchicine,
      indicates that the MN-PCE appear in the blood stream at almost the same time, as
      occurs after the exposure to gamma rays; in spite of the differences in the cell
      cycle stage in which they can cause micronucleus (MN). Perhaps the fact that
      cells are not synchronized does not permit one to observe some difference in the
      time they appear in the blood. These results suggest that colchicine acts rapidly
      after exposure. The elimination half-life of colchicine is 17h, suggesting that
      colchicne is disposable for long time. With high doses of colchicine the
      pharmacokinetic parameters increases substantially. These data imply that low
      doses of colchicine are slightly cytotoxic, and that under this circumstances
      colchicines arrives rapidly to hemopoyetic tissues and acts for several hours.

PMID- 11448643
TI  - Potent antimutagenic activity of white tea in comparison with green tea in the
      Salmonella assay.
AB  - There is growing interest in the potential health benefits of tea, including the
      antimutagenic properties. Four varieties of white tea, which represent the least
      processed form of tea, were shown to have marked antimutagenic activity in the
      Salmonella assay, particularly in the presence of S9. The most active of these
      teas, Exotica China white tea, was significantly more effective than Premium
      green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5
      f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies
      were performed using rat liver S9 in assays for methoxyresorufin O-demethylase
      (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic
      amines, as well as Salmonella assays with the direct-acting mutagen 2
      hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low
      concentrations in the assay inhibited MROD activity, and attenuated the mutagenic
      activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents
      found in green tea also were detected in white tea, including high levels of
      epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major
      constituents were mixed to produce "artificial" teas, according to their relative
      levels in white and green teas, the complete tea exhibited higher antimutagenic
      potency compared with the corresponding artificial tea. The results suggest that
      the greater inhibitory potency of white versus green tea in the Salmonella assay
      might be related to the relative levels of the nine major constituents, perhaps
      acting synergistically with other (minor) constituents, to inhibit mutagen
      activation as well as "scavenging" the reactive intermediate(s).

PMID- 11448644
TI  - Differential sensitivity of Chinese hamster V79 and Chinese hamster ovary (CHO)
      cells in the in vitro micronucleus screening assay.
AB  - Both the V79 and CHO cell lines are routinely used in the in vitro MN screening
      assay for the detection of possible genotoxicants. The CHO cell line is the
      predominant cell line currently used in the genetic toxicology testing industry.
      However, some laboratories routinely utilize the V79 cell line since the in vitro
      MN screening assay was initially developed using V79 cells. Our laboratory has
      historically used the CHO cell line. Therefore, our laboratory was interested in
      comparing the two cell lines with regard to possible similarities or differences
      in MN induction sensitivity after exposure to cyclophosphamide (CPA) and
      mitomycin C (MMC), the two standard positive control chemicals routinely used in
      this assay. Three exposure conditions in the presence of CPA and MMC were
      examined in both cell lines. Replicate cultures of CHO cells in McCoy's 5A and
      V79 cells in both McCoy's 5A and E-MEM were established and treated with 5 microg
      CPA/ml (4h exposure with S9), 0.5 microg MMC (4h exposure without S9) and 0.5
      microg MMC (24h exposure without S9). A total of 400 cytochalasin B-blocked
      binucleated cells and 200 consecutive cells were analyzed from each culture for
      MN and cell cycle kinetics, respectively. Analysis of the data demonstrated that
      CHO cells were up to approximately five-fold more sensitive to the induction of
      CPA- and MMC-induced MN than V79 cells. Both cell lines exhibited similar average
      generation times among identical exposure groups. Therefore, the difference in MN
      sensitivity cannot be attributed to possible differences in cell cycle kinetics
      and is possibly related to inherent cellular differences in the processing of
      and/or repair of CPA- and MMC-induced damage by V79 and CHO cells.

PMID- 11448645
TI  - Optimization of ENU mutagenesis of Caenorhabditis elegans.
AB  - Chemical mutagenesis of Caenorhabditis elegans has relied primarily on EMS to
      produce missense mutations. The drawback of EMS mutagenesis is that the molecular
      lesions are primarily G/C --> A/T transitions. ENU has been shown to produce a
      different spectrum of mutations, but its greater toxicity to C. elegans makes it
      a difficult mutagen to use. We describe here methods for minimizing ENU toxicity
      in C. elegans. Methods include preparing ENU stocks in absolute ethanol and
      storing stock solutions for not more than 2 weeks at -20 degrees C. To maintain
      reasonable brood sizes of mutagenized animals, mutagenic solutions should not
      exceed 1.0mM ENU. We provide data which suggest ENU is degraded or altered to
      more toxic products in aqueous solution, but less so in solvents such as absolute
      ethanol.

PMID- 11448646
TI  - Musk ketone enhances benzo(a)pyrene induced mutagenicity in human derived Hep G2
      cells.
AB  - Musk ketone is a widely used artificial fragrance which has been identified in
      human fatty tissue and milk. The mutagenic and comutagenic effects of this
      compound were studied in micronucleus tests with a human derived hepatoma cell
      line (Hep G2). Exposure of the cells to MK alone in the range between 5 and 5000
      ng/ml did not cause induction of MN. When the cells were treated simultaneously
      with MK (5-5000 ng/ml) and 0.2 microg/ml benzo(a)pyrene, no synergistic effects
      were detected; benzo(a)pyrene (B(a)P) itself caused an 1.5-fold increase of MN
      over the spontaneous background frequency (60 versus 39 MN/1000 binucleated
      cells). In a third experimental series, the cells were pretreated with MK for 28h
      and subsequently exposed to 0.2 microg/ml B(a)P. In this case, a pronounced
      comutagenic effect was observed: The LOAEL for MK was 0.05 microg/ml. With higher
      doses (0.5, 1.0 and 5.0 microg MK/ml), a significant increase of B(a)P induced MN
      frequencies was measured, the induction rates being 50, 66, and 88%,
      respectively. Additional measurements of 7-ethoxyresorufin deethylase indicated
      that MK induces cytochrome P450 isoenzymes (1A1) which play a key role in the
      activation of B(a)P. The results of the present study show that MK amplifies the
      genotoxic effects of B(a)P in human derived cells and indicate that exposure of
      humans to MK might increase their susceptibility to the health hazards of B(a)P
      and other polycyclic aromatic hydrocarbons.

PMID- 11448647
TI  - Effect of various alkyl and unsaturated substituents on the mutagenicity of some
      nitrophenyl thioethers.
AB  - A variety of nitro-substituted phenyl alkyl/aryl thioethers and nitroso
      substituted phenyl alkyl/aryl thioethers have been synthesized and tested for
      their mutagenicity towards Salmonella typhimurium strain TA100, TA98, TA98NR and
      TA98/1,8-DNP(6) in the absence of S9 mix. The relative order of mutagenicity in
      TA98 and TA100 among p-nitrophenyl thioethers having alkyl or aryl substituents
      is allyl>phenyl>benzyl>butyl>propyl>ethyl>methyl. Compounds having an alkyl chain
      C(6) to C(12) were found to be non-mutagenic. Among the various positional
      isomers (ortho, meta and para) of nitro-substituted diphenyl thioethers only the
      compounds having the -NO(2) function at the para position is mutagenic, whereas
      compounds having a -NO(2) function at ortho and meta are non-mutagenic. However,
      the reduced intermediate, ortho-nitroso derivative was found to be mutagenic in
      all the four strains but the meta-nitroso derivative was found to be non
      mutagenic. All mutagens were found to be non-mutagenic when tested in
      nitroreductase deficient strain TA98NR, whereas their nitroso intermediates are
      found to be mutagenic. A substantial fall in the mutagenic activity is observed
      when some mutagens are tested in O-acetyltransferase deficient strain TA98/1,8
      DNP(6).

PMID- 11448648
TI  - Host determinants of DNA alkylation and DNA repair activity in human colorectal
      tissue: O(6)-methylguanine levels are associated with GSTT1 genotype and O(6)
      alkylguanine-DNA alkyltransferase activity with CYP2D6 genotype.
AB  - There is increasing evidence that alkylating agent exposure may increase large
      bowel cancer risk and factors which either alter such exposure or its effects may
      modify risk. Hence, in a cross-sectional study of 78 patients with colorectal
      disease, we have examined whether (i) metabolic genotypes (GSTT1, GSTM1, CYP2D6,
      CYP2E1) are associated with O(6)-methyldeoxyguanosine (O(6)-MedG) levels, O(6)
      alkylguanine-DNA alkyltransferase (ATase) activity or K-ras mutations, and (ii)
      there was an association between ATase activity and O(6)-MedG levels. Patients
      with colon tumours and who were homozygous GSTT1(*)2 genotype carriers were more
      likely than patients who expressed GSTT1 to have their DNA alkylated (83 versus
      32%, P=0.03) and to have higher O(6)-MedG levels (0.178+/-0.374 versus 0.016+/
      0.023 micromol O(6)-MedG/mol dG, P=0.04) in normal, but not tumour, DNA. No such
      association was observed between the GSTT1 genotype and the frequency of DNA
      alkylation or O(6)-MedG levels in patients with benign colon disease or rectal
      tumours. Patients with colon tumours or benign colon disease who were CYP2D6-poor
      metabolisers had higher ATase activity in normal tissue than patients who were
      CYP2D6 extensive metabolisers or CYP2D6 heterozygotes. Patients with the CYP2E1
      Dra cd genotype were less likely to have a K-ras mutation: of 55 patients with
      the wild-type CYP2E1 genotype (dd), 23 had K-ras mutations, whereas none of the 7
      individuals with cd genotype had a K-ras mutation (P=0.04). No other associations
      were observed between GSTT1, GSTM1, CYP2D6 and CYP2E1 Pst genotypes and adduct
      levels, ATase activity or mutational status. O(6)-MedG levels were not associated
      with ATase activity in either normal or tumour tissue. However, in 15 patients
      for whom both normal and tumour DNA contained detectable O(6)-MedG levels, there
      was a strong positive association between the normal DNA/tumour DNA adduct ratio
      and the normal tissue/tumour tissue ATase ratio (r(2)=0.66, P=0.001). These
      results indicate that host factors can affect levels both of the biologically
      effective dose arising from methylating agent exposure and of a susceptibility
      factor, the DNA repair phenotype.

PMID- 11448649
TI  - o-Phenylenediamine-induced DNA damage and mutagenicity in tobacco seedlings is
      light-dependent.
AB  - Of the three isomers of the aromatic amine phenylenediamine (PDA), only o-PDA,
      but not m- and p-PDA, induced DNA damage (as measured by the Comet assay), and
      somatic mutations in the leaves of the chlorophyll-deficient tester strain
      Nicotiana tabacum var. xanthi. With increasing light intensity (0, 30, 80 or 140
      micromol m(-2)s(-1) photosynthetic photon fluence rate) during a 72h mutagenic
      treatment of tobacco seedlings, o-PDA-induced DNA damage and the yield of somatic
      mutations were significantly increased. The peroxidase inhibitor
      diethyldithiocarbamate (DEDTC) repressed o-PDA-induced DNA damage. The effect of
      light is caused by the light-dependent increase of peroxidase activity and the
      accumulation of hydrogen peroxide, which participate in the metabolic activation
      of the promutagen o-PDA to mutagenic product(s). In contrast, DNA damage induced
      by the direct-acting alkylating mutagen ethyl methanesulphonate was the same
      whether treatment was in the light or in the dark, and was not repressed by the
      peroxidase inhibitor DEDTC.

PMID- 11448650
TI  - Evaluation of the general suitability of the rat for the micronucleus assay: the
      effect of cyclophosphamide in 14 strains.
AB  - To evaluate the general suitability of the rat for the micronucleus assay, we
      conducted the assay in males of 14 different strains, 13 inbred (ACI, BN, BUF,
      COP, DRH, F344, IS, LEW, RCS, SHR, WAG, WKYO, WTC) and 1 outbred (SD), using
      cyclophosphamide as the test chemical. Cyclophosphamide at 0 (vehicle), 5, 10, or
      20mg/kg per day was administered orally twice, 24h apart, to five rats per dosage
      group. Bone marrow and peripheral blood were collected 24h after the second
      treatment. All 14 strains showed a positive response to cyclophosphamide, with
      slight differences in sensitivity. We concluded that the rat is suitable for the
      micronucleus assay regardless of strain.

PMID- 11448651
TI  - Antimutagenic activity of organosulfur compounds from Allium is associated with
      phase II enzyme induction.
AB  - In a previous study, we showed that naturally occurring organosulfur compounds
      (OSCs) from garlic and onion modulated the activation of carcinogen via the
      alteration of cytochromes P450. The present study was undertaken to determine the
      incidence of the in vivo induction of phase II enzymes by individual OSCs on the
      genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide
      (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered
      by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects
      of treatments on phase II enzymes and on the genotoxicity of carcinogens were
      evaluated with hepatic cytosols and microsomes from OSCs-treated rats. DADS
      strongly increased all the phase II enzymes activities examined, i.e. total
      glutathione S-transferase (GST) activity, mu GST activity, quinone reductase (QR)
      activity and epoxide hydrolase (EH) activity. In addition, DADS strongly
      increased the protein level of rGSTP1. QR activity, total and mu GST activities
      were also increased by DAS and DPDS whereas DPS increased only mu GST activity
      and QR activity. To assess the repercussions of these inductions on the
      genotoxicity of carcinogens, the effects of cytosols or microsomes from OSCs
      treated rats on the mutagenicity of (+)-anti-7beta,8alpha-dihydroxy
      9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), styrene oxide (SO)
      and 4-nitroquinoline 1-oxide (4-NQO) were measured in the Ames test. DADS showed
      a very effective antimutagenic activity against BPDE, SO and 4-NQO. DAS reduced
      the mutagenicity of BPDE and SO. In contrast, DPS and DPDS showed little
      efficient antimutagenic activity since they only reduced the mutagenicity of BPDE
      and 4-NQO, respectively. Interestingly, DADS appeared to be as effective as
      ethoxyquin, a model inducer of phase II enzymes, in both inducing phase II
      enzymes and inhibiting the mutagenicity of carcinogens. This study demonstrated
      that the antimutagenic activities of OSCs against several ultimate carcinogens
      were closely related to their ability to induce phase II enzymes.

PMID- 11448652
TI  - Micronuclei in peripheral blood lymphocytes and buccal epithelial cells of Polish
      farmers exposed to pesticides.
AB  - In this biomonitoring study, we investigated whether an occupational exposure to
      a complex mixture of chemical pesticides produced a significant increase of
      micronuclei (MN) in both peripheral blood lymphocytes and buccal cells. Forty
      nine male workers exposed to pesticides, from an agricultural area of Malopolska
      Region in Southern Poland, together with 50 men from the same area without
      indication of exposure to pesticides that served as controls, were used in this
      investigation. No statistically significant differences in the frequencies of
      cytogenetic damage were detected between exposed and control individuals, for
      either type of cells. The multiple linear regression analysis in the case of
      lymphocytes indicated that the studied cytogenetic endpoints were inversely
      influenced by alcohol; whilst a negative binomial regression, in the case of
      buccal cells, indicated that the MN values were directly influenced by the
      ingestion of red meat. An inverse negative relationship between the cytokinesis
      block proliferation index and age, and a significant increase of miscarriages due
      to the exposure to pesticides were also observed.

PMID- 11448653
TI  - Human cell mutagenicity of chlorinated and unchlorinated water and the
      disinfection byproduct 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX).
AB  - Extracts of three water samples--humic acid-enriched water-both peatland water
      and drinking water, both with and without chlorination were tested for
      mutagenicity at the tk locus in MCL-5 cells, a line of human B-lymphoblastoid
      cells that express cytochrome P450 enzymes and microsomal epoxide hydrolase. Our
      results show that chlorination caused a 5.5-fold increase (P<0.0001) in the
      mutagenicity of the humic acid-enriched water. The unchlorinated peatland water
      was mutagenic at the two highest doses (240 and 480 microg equivalent total
      organic carbon (TOC)/ml), possibly due to polycyclic aromatic hydrocarbons (PAH)
      that were measured in the peat. In contrast, the chlorinated peatland water was
      non-mutagenic at low doses, while at the highest dose (240 microg equivalent
      TOC/ml) the sample was so toxic that an insufficient number of cells survived
      treatment to allow plating. The chlorinated and unchlorinated drinking water were
      both non-mutagenic. 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a
      potent bacterial mutagen and chlorine-disinfection byproduct, was also tested in
      MCL-5 cells as well as in two other human B-lymphoblastoid cell-lines, AHH-1 TK+/
      and h1A1v2 cells, which differ from each other and from MCL-5 cells in the
      amounts of cytochrome P450 enzymes they can express. MX was mutagenic to all
      three cell-lines, but there was no apparent correlation between cytochrome P450
      enzyme expression and the mutagenicity of MX. Overall, our results show that
      samples of chlorinated humic acid-enriched water and MX, a model chlorine
      disinfection byproduct, are moderately mutagenic to human cells.

PMID- 11448654
TI  - Self-monitoring of blood glucose levels and glycemic control: the Northern
      California Kaiser Permanente Diabetes registry.
AB  - PURPOSE: We sought to evaluate the effectiveness of self-monitoring blood glucose
      levels to improve glycemic control. SUBJECTS AND METHODS: A cohort design was
      used to assess the relation between self-monitoring frequency (1996 average daily
      glucometer strip utilization) and the first glycosylated hemoglobin (HbA1c) level
      measured in 1997. The study sample included 24,312 adult patients with diabetes
      who were members of a large, group model, managed care organization. We estimated
      the difference between HbA1c levels in patients who self-monitored at frequencies
      recommended by the American Diabetes Association compared with those who
      monitored less frequently or not at all. Models were adjusted for age, sex, race,
      education, occupation, income, duration of diabetes, medication refill adherence,
      clinic appointment "no show" rate, annual eye exam attendance, use of
      nonpharmacological (diet and exercise) diabetes therapy, smoking, alcohol
      consumption, hospitalization and emergency room visits, and the number of daily
      insulin injections. RESULTS: Self-monitoring among patients with type 1 diabetes
      (> or = 3 times daily) and pharmacologically treated type 2 diabetes (at least
      daily) was associated with lower HbA1c levels (1.0 percentage points lower in
      type 1 diabetes and 0.6 points lower in type 2 diabetes) than was less frequent
      monitoring (P < 0.0001). Although there are no specific recommendations for
      patients with nonpharmacologically treated type 2 diabetes, those who practiced
      self-monitoring (at any frequency) had a 0.4 point lower HbA1c level than those
      not practicing at all (P < 0.0001). CONCLUSION: More frequent self-monitoring of
      blood glucose levels was associated with clinically and statistically better
      glycemic control regardless of diabetes type or therapy. These findings support
      the clinical recommendations suggested by the American Diabetes Association.

PMID- 11448655
TI  - Pioglitazone hydrochloride in combination with sulfonylurea therapy improves
      glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo
      controlled study.
AB  - PURPOSE: To evaluate the efficacy and tolerability of pioglitazone in combination
      with a sulfonylurea in the treatment of type 2 diabetes mellitus. SUBJECTS AND
      METHODS: This 16-week, double-blind study included patients on a stable regimen
      of a sulfonylurea for > or = 30 days and with a glycosylated hemoglobin (HbA1C)
      level > or = 8.0%. Patients were randomly assigned to receive once daily
      pioglitazone 15 mg (n = 184), pioglitazone 30 mg (n = 189), or placebo plus
      sulfonylurea (n = 187). RESULTS: Patients receiving pioglitazone + sulfonylurea
      had significant (P < 0.05) decreases from baseline in HbA1C and fasting plasma
      glucose levels compared with patients treated with placebo + sulfonylurea. As
      compared with placebo, HbA1C decreased by 0.9% (95% confidence interval [CI]:
      0.06% to 1.2%) with pioglitazone 15 mg and 1.3% (CI: 1% to 1.6%) with 30 mg
      pioglitazone; fasting plasma glucose levels decreased by 39 mg/dL (95% CI: 27 to
      52 mg/dL) with pioglitazone 15 mg and by 58 mg/dL (95% CI: 46-70 mg/dL) with 30
      mg pioglitazone. Both pioglitazone + sulfonylurea groups had significant (P <
      0.05) mean percent decreases in triglyceride levels (17%, 95% CI: 6% to 27% for
      15 mg; 26%, 95% CI: 16% to 36% for 30 mg) and increases in high-density
      lipoprotein cholesterol levels (6%, 95% CI: 1% to 11% for 15 mg; 13%, CI: 8% to
      18% for 30 mg) compared with placebo + sulfonylurea. There were small but
      statistically significant mean percent increases in low-density lipoprotein
      cholesterol levels in all groups. Pioglitazone was well tolerated, and the rates
      of adverse events were similar in all groups. CONCLUSION: In patients with type 2
      diabetes, pioglitazone plus sulfonylurea significantly improves HbA1C and fasting
      plasma glucose levels with beneficial effects on serum triglyceride and HDL
      cholesterol levels.

PMID- 11448656
TI  - Exercise echocardiography for the prognostic stratification of patients with low
      pretest probability of coronary artery disease.
AB  - PURPOSE: The aim of this study was to determine whether exercise echocardiography
      provides incremental data for risk stratification of patients with a low pretest
      probability of coronary artery disease. PATIENTS AND METHODS: The study included
      patients referred for exercise echocardiography whose probability of coronary
      artery disease was 25% or less. We calculated an exercise wall motion score index
      (on a 1-5 scale), an indicator of the extent and severity of exercise-induced
      abnormalities. The primary outcomes of the study were subsequent cardiac events
      (cardiac death and nonfatal myocardial infarction). RESULTS: We studied 571 men
      and 1047 women; their mean (+/- SD) age was 55 +/- 13 years. During a median
      follow-up of 3 years, there were 19 cardiac events (6 cardiac deaths and 13
      nonfatal myocardial infarctions); an additional 37 patients underwent coronary
      revascularization. In a multivariate analysis of clinical, exercise
      electrocardiographic, and echocardiographic parameters, exercise wall motion
      score index (hazard ratio [HR] = 2.1 per 0.5 units; 95% confidence interval [CI]:
      1.3 to 3.4), and age (HR = 2.0 per decade; 95% CI: 1.2-2.8) were independently
      associated with the risk of cardiac events. Although exercise echocardiographic
      variables contributed significantly (P = 0.01) to a model of the risk of adverse
      events, only 9 (47%) of the 19 patients with cardiac events were identified by an
      abnormal exercise echocardiogram. CONCLUSION: Among patients with low pretest
      probability of coronary artery disease by clinical criteria, exercise
      echocardiography identifies some, but not all, patients at risk of future events.
      Because of the low event rate, routine application of exercise echocardiography
      in a patient with a low pretest probability does not appear to be cost-effective
      and therefore cannot be recommended.

PMID- 11448657
TI  - Quality of ambulatory care after myocardial infarction among Medicare patients by
      type of insurance and region.
AB  - PURPOSE: To evaluate use of effective cardiac medications and rehabilitation
      after myocardial infarction in the ambulatory setting in health maintenance
      organizations (HMOs) and fee-for-service care, and by region. SUBJECTS AND
      METHODS: We surveyed elderly Medicare patients during 1996 and 1997 in California
      (n = 516), Florida (n = 304), and the Northeast (n = 220; Massachusetts, New
      York, and Pennsylvania) approximately 18 months after myocardial infarction. We
      assessed use of cardiac medications and rehabilitation for HMO (n = 520) and fee
      for-service (n = 520) patients matched by age, sex, month of infarct, and region.
      RESULTS: Across all regions, similar proportions of HMO and fee-for-service
      patients were using aspirin (72%, n = 374 vs. 74%, n = 387), beta-blockers (38%,
      n = 195 vs. 32%, n = 168), angiotensin-converting enzyme inhibitors (31%, n = 159
      vs. 29%, n = 148), cholesterol-lowering agents (28%, n = 146 vs. 30%, n = 157),
      and calcium channel blockers (31%, n = 162 vs. 31%, n = 159; all P >0.07), except
      in California where more HMO patients received beta-blockers (36%, n = 93 vs.
      26%, n = 66, P = 0.01). In adjusted analyses, use of these drugs did not differ
      significantly between HMO and fee-for-service patients. Substantial regional
      differences were evident in the use of beta-blockers (Northeast 46%, n = 102;
      Florida 34%, n = 102; California 31%, n = 159) and cholesterol-lowering agents
      (California 35%, n = 182; Florida 24%, n = 73; Northeast 22%, n = 48; each P
      <0.001). Fee-for-service patients were more likely than HMO patients to receive
      cardiac rehabilitation in unadjusted (32%, n = 167, vs. 22%, n = 141, P = 0.001)
      and adjusted analyses. CONCLUSIONS: Both HMO and fee-for-service patients would
      likely benefit from greater use of beta-blockers and cholesterol-lowering agents.
      Professional fees for cardiac rehabilitation may promote increased use among fee
      for-service patients. Future studies should assess the quality of ambulatory
      cardiac care in different types of HMOs and the reasons for geographic variations
      in cardiac drug use.

PMID- 11448658
TI  - Life expectancy and cancer risk in patients with Barrett's esophagus: a
      prospective controlled investigation.
AB  - BACKGROUND: It has been suggested that patients with Barrett's esophagus have a
      substantially increased risk of esophageal and possibly extra-esophageal cancers.
      We compared the incidence of cancer and the survival rates of patients with
      Barrett's esophagus with those observed in patients with achalasia, with
      Schatzki's ring, and in the general population. PATIENTS AND METHODS: From 1980
      through 1994, 60 consecutive patients with newly diagnosed long-segment Barrett's
      esophagus without dysplasia were seen in a single gastroenterology consultation
      office and followed until the Fall of 1999. Cancer incidence and survival rates
      were compared with age- and sex-matched patients with symptomatic Schatzki's ring
      (n = 60) and achalasia (n = 60). Survival data were also compared with those of
      the German population. RESULTS: During a mean (+/-SD) observation period of 10 +/
      5 years, 2 patients with Barrett's esophagus (3%; 95% confidence interval [CI]:
      0% to 11%) developed esophageal cancer, and 9 (15%; 95% CI: 7% to 27%) developed
      extra-esophageal cancers. These data differed only slightly from those of
      patients with Schatzki's ring (esophageal cancer: n = 1, 2%; 95% CI: 0% to 9%;
      extra-esophageal cancers: n = 9, 15%; 95% CI: 7%-27%) and achalasia (no
      esophageal cancers, extra-esophageal cancers: n = 3, 5%; 95% CI: 1% to 4%).
      Estimated 10-year survival was similar in patients with Barrett's esophagus
      (83%), patients with symptomatic Schatzki's ring (80%), patients with achalasia
      (87%), and in the general population (82%). CONCLUSIONS: The cancer risk in
      patients with Barrett's esophagus has been overestimated. If patients with
      nondysplastic epithelium are followed, the risk of esophageal cancer is about 1
      per 300 patient-years.

PMID- 11448659
TI  - Hospice enrollment and hospitalization of dying nursing home patients.
AB  - PURPOSE: This study's purpose was to evaluate whether Medicare hospice care
      provided in nursing homes is associated with lower hospitalization rates.
      SUBJECTS AND METHODS: This retrospective cohort study included nursing home
      residents in five states who enrolled in hospice between 1992 and 1996 (n =
      9202), and who died before 1998. For each hospice patient, 3 nonhospice residents
      (2 in 106 instances) were chosen (n = 27,500). Medicare claims identified hospice
      enrollment and acute care hospitalizations. RESULTS: Twenty-four percent of
      hospice and 44% of nonhospice residents were hospitalized in the last 30 days of
      life. Adjusting for confounders, hospice patients were less likely than
      nonhospice residents to be hospitalized (odds ratio 0.43; 95% confidence interval
      [CI]: 0.39 to 0.46). Considering all of nonhospice residents who died (n =
      226,469), those in facilities with no hospice had a 47% hospitalization rate,
      whereas rates were 41% in facilities with low hospice use and 39% in facilities
      with moderate hospice use (5%+ of patients in hospice). Hospitalization was less
      likely for nonhospice residents in facilities with low hospice use (odds ratio
      0.82; 95% CI: 0.80 to 0.84) and moderate hospice use (odds ratio 0.71; 95% CI:
      0.69 to 0.74), compared with those in facilities with no hospice. CONCLUSIONS:
      When integrated into the nursing home care processes, hospice care is associated
      with less hospitalization for Medicare hospice patients. Additionally, possibly
      through diffusion of palliative care philosophy and practices, nonhospice
      residents who died in nursing homes having a hospice presence had lower rates of
      end-of-life hospitalizations.

PMID- 11448660
TI  - The role of adenosine 5'-diphosphate receptor blockade in patients with
      cardiovascular disease.
AB  - Aspirin, which has been the mainstay of antiplatelet agent for many decades,
      affects a single pathway in the platelet activation process and provides
      incomplete protection against cardiovascular events. Aspirin also may blunt the
      hemodynamic effect of angiotensin-converting enzyme inhibitors. Dipyridamole may
      provide some additional benefit, but there is little evidence to suggest its
      superiority alone or in combination with aspirin compared to standard doses of
      aspirin. Oral platelet glycoprotein IIb/IIIa inhibitors, although initially
      promising, have had disappointing results in recent clinical studies. A new class
      of medications, the thienopyridines, blocks the activity of platelet adenosine 5'
      diphosphate (ADP) receptors, thereby reducing platelet activation. This review
      discusses the pharmacology, clinical studies, and potential uses of these agents,
      which include ticlopidine and clopidogrel. ADP inhibitors, by blocking an
      alternate pathway of platelet activation, are slightly more effective than
      aspirin in reducing cardiovascular events.

PMID- 11448661
TI  - Treatment of chronic headache with antidepressants: a meta-analysis.
AB  - BACKGROUND: Although antidepressants are often used for preventing chronic
      headache, their effectiveness is uncertain. METHODS: We performed a meta-analysis
      of English-language, randomized placebo-controlled trials of antidepressants as
      prophylaxis for chronic headache. RESULTS: Thirty-eight trials were included.
      Because some compared more than one drug with placebo, 44 study arms were
      combined using a random effects model. Twenty-five studies focused on migraines,
      12 on tension headaches, and 1 on both. Nineteen used tricyclic antidepressants,
      18 serotonin antagonists, and 7 selective serotonin reuptake inhibitors. Patients
      receiving antidepressants were twice as likely to report headache improvement
      (rate ratio [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.4). Because 31%
      (95% CI: 23% to 40%) more treated patients improved than those receiving placebo,
      clinicians would need to treat 3.2 patients for 1 patient to improve. The average
      amount of improvement (standardized mean difference) was 0.94 (95% CI: 0.65 to
      1.2), an effect considered large. Treated patients also consumed less analgesic
      medication (standardized mean difference, -0.7; 95% CI: -0.5 to -0.94). There
      were no differences in outcomes among the three classes of agents studied or by
      the type of headache (migraine vs. tension), quality score, length of treatment,
      or percentage of patients lost to follow-up. Assessment of depression across
      studies was insufficient to determine if the effects were independent of
      depression. CONCLUSION: Antidepressants are effective in preventing chronic
      headaches. Whether this is independent of depression and whether there are
      differences in efficacy by class of agent needs further study.

PMID- 11448662
TI  - Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to
      traditional nonsteroidal anti-inflammatory drugs.

PMID- 11448663
TI  - Usefulness and complications of thoracentesis in cirrhotic patients.

PMID- 11448665
TI  - A new era in type 2 diabetes mellitus treatment?

PMID- 11448666
TI  - Assessing cardiac risk--how low (risk) should you go?

PMID- 11448667
TI  - Quality in managed care: promise versus reality.

PMID- 11448668
TI  - Expectations of and for the medical director of the resident's ambulatory clinic.

PMID- 11448669
TI  - Synthesis of L-arabinitol and xylitol monomers for the preparation of polyamides.
      Preparation of an L-arabinitol-based polyamide.
AB  - Dihydrochlorides of 1,5-diamino-1,5-dideoxy-2,3,4-tri-O-methyl-L-arabinitol (and
      xylitol) and pentachlorophenyl esters of 2,3,4-tri-O-methyl-L-arabinaric (and
      xylaric) acids have been prepared as suitable bifunctional monomers for linear
      polycondensations. A new aregic AABB-type L-arabinitol-based polyamide is also
      described from the corresponding monomers. It was crystalline with T(m) 250
      degrees C, optically active, and soluble in the usual organic solvents, including
      chloroform, and in water. Its M(w) obtained by GPC was 27,500 with a
      polydispersity of 1.4.

PMID- 11448670
TI  - Stereoselective synthesis of 2-S-ethyl(phenyl)-2-thio-beta-glucopyranosides via
      1,2-migration and concurrent glycosidation of ethyl(phenyl) 2,3-orthoester-1-thio
      alpha-mannopyranosides.
AB  - 1,2-Migration and concurrent glycosidation of ethyl(phenyl) 2,3-orthoester-1-thio
      alpha-D- and L-mannopyranosides under the action of TMSOTf readily afforded the
      corresponding 2-S-ethyl(phenyl)-2-thio-beta-glucopyranosides, ready precursors to
      2-deoxy-arabino-hexopyranosides (2-deoxy-beta-glucopyranosides).

PMID- 11448671
TI  - Synthesis of an aza analogue of 2-deoxy-D-ribofuranose and its homologues.
AB  - Azasugars were obtained in one-pot reactions by catalytic reduction reactions of
      amino group precursors in aldosugars followed by intramolecular reductive amino
      alkylation reactions. (3R,4S)-4-[(1S)-1,2-Dihydroxyethyl]pyrrolidin-3-ol was
      obtained from D-xylose by two different strategies through 3-C-cyano-3-deoxy-D
      ribo-pentofuranose or 3-C-azidomethyl-3-deoxy-D-ribo-pentofuranose in 6 and 16%
      overall yields, respectively. The oxidative cleavage of the diol group in the
      corresponding Fmoc-azasugar followed by deprotection afforded (3R,4R)-4
      (hydroxymethyl)pyrrolidin-3-ol. (3R,4S)-4-[(1S,2R)-1,2,3
      Trihydroxypropyl]pyrrolidin-3-ol was synthesized from diacetone-D-glucose through
      3-deoxy-3-C-nitromethyl-D-allose and the overall yield was 7%.

PMID- 11448672
TI  - Synthesis of beta-D-galactofuranosyl nucleoside analogues. A new type of beta-D
      galactofuranosidase inhibitor.
AB  - The development of beta-D-galactofuranosidase inhibitors provides a good
      chemotherapeutic target for treatment of major human diseases, because beta-D
      galactofuranose is a constituent of important pathogen microorganisms but is
      absent in mammals. With this purpose we have prepared beta-D-galactofuranosyl
      nucleoside analogues, derived by the addition of nucleophiles to perbenzoylated
      beta-D-galactofuranosyl isothiocyanate, a compound previously prepared in this
      laboratory. N-beta-D-Galactofuranosyl-O-ethylthiourethane, N-beta-D
      galactofuranosyl-4-oxoimidazolidine-2-thione, N-beta-D-galactofuranosyl-4
      imidazoline-2-thione, and N-beta-D-galactofuranosyl-4-methoxyimidazolidine-2
      thione, were prepared. The biological assays showed that imidazoline and
      imidazolidine-2-thione derivatives act as a new type of exo beta-D
      galactofuranosidase inhibitor.

PMID- 11448673
TI  - Chemoenzymatic synthesis of 2-chloro-4-nitrophenyl beta-maltoheptaoside acceptor
      products using glycogen phosphorylase b.
AB  - In the present work, we aimed at developing a chemoenzymatic procedure for the
      synthesis of beta-maltooligosaccharide glycosides. The primer in the enzymatic
      reaction was 2-chloro-4-nitrophenyl beta-maltoheptaoside (G(7)-CNP), synthesised
      from beta-cyclodextrin using a convenient chemical method. CNP
      maltooligosaccharides of longer chain length, in the range of DP 8-11, were
      obtained by a transglycosylation reaction using alpha-D-glucopyranosyl-phosphate
      (G-1-P) as a donor. Detailed enzymological studies revealed that the conversion
      of G(7)-CNP catalysed by rabbit skeletal muscle glycogen phosphorylase b (EC
      2.4.1.1) could be controlled by acarbose and was highly dependent on the
      conditions of transglycosylation. More than 90% conversion of G(7)-CNP was
      achieved through a 10:1 donor-acceptor ratio. Tranglycosylation at 37 degrees C
      for 30 min with 10 U enzyme resulted in G(8-->12)-CNP oligomers in the ratio of
      22.8, 26.6, 23.2, 16.5, and 6.8%, respectively. The reaction pattern was
      investigated using an HPLC system. The preparative scale isolation of G(8-->11)
      CNP glycosides was achieved on a semipreparative HPLC column. The productivity of
      the synthesis was improved by yields up to 70-75%. The structures of the
      oligomers were confirmed by their chromatographic behaviours and MALDI-TOF MS
      data.

PMID- 11448674
TI  - Preparation and characterisation of oligosaccharides produced by nitrous acid
      depolymerisation of chitosans.
AB  - Two chitosans with widely different chemical composition (fraction of N
      acetylated units (F(A))<0.001 and F(A)=0.59), were degraded by nitrous acid, to
      obtain the reactive 2,5-anhydro-D-mannose- (M-) unit at the new reducing end. The
      fully N-acetylated and fully N-deacetylated oligomers were separated by size
      exclusion chromatography. Both the chemical structure and purity were studied by
      one- and two-dimensional 1H and 13C NMR methods. The fully N-acetylated oligomers
      were found to be stable, whereas the N-deacetylated oligomers reacted
      intermolecularly by a Schiff base reaction between the 2-amino group on the N
      deacetylated units and the M-units, facilitating the cleavage of the glycosidic
      bond next to the M-unit and the formation of 5-hydroxymethylfurfural (HMF).

PMID- 11448675
TI  - The crystal structure of the 1:1 inclusion complex of beta-cyclodextrin with
      squaric acid.
AB  - The crystal and molecular structure of the 1:1 inclusion complex of beta
      cyclodextrin (cyclomaltoheptaose) with squaric acid (3,4-dihydroxycyclobutene-1,2
      dione) was determined by X-ray diffraction. The complex crystallizes in the
      monoclinic P2(1) space group and belongs to the monomeric cage-type,
      characterized by a herringbone-like packing motif. Co-crystallized water
      molecules are present on seven sites, of which six are fully occupied. The guest
      molecule is placed inside the beta-cyclodextrin cavity, perpendicular to the
      plane defined by the glycosidic O-4n atoms, and held in place by direct and water
      mediated hydrogen bonds mainly involving symmetry-related beta-cyclodextrin
      molecules. The accommodation of the planar guest molecule into the beta
      cyclodextrin cavity determines a significant distortion of the latter from the
      sevenfold symmetry.

PMID- 11448676
TI  - Reaction of D-glycals with azidotrimethylsilane.
AB  - The treatment of 2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enitol with
      azidotrimethylsilane by the aid of a catalytic amount of Yb(OTf)(3) afforded
      2,4,6-tri-O-acetyl-2,3-dideoxy-alpha-D-erythro-hex-2-enopyranosyl azide in high
      yield.

PMID- 11448677
TI  - High yielding one-pot enzyme-catalyzed synthesis of UDP-glucose in gram scales.
AB  - Uridine diphosphoglucose is an important cofactor of glucosylating enzymes. A
      simple and high yielding one-pot enzymatic synthesis of UDPG on a gram scale from
      glucose via hexokinase, phosphoglucomutase and UDPG pyrophosphorylase (UGPase) is
      described. Repetitive addition of substrate was used to avoid inhibition of
      UGPase. The approach allows recovery of active enzymes and their re-use. The
      synthesis of UDP-[4-(13)C]-glucose on a 0.5 g scale resulted in a final yield of
      70% and a purity of >95% after chromatographic purification.

PMID- 11448678
TI  - Studies of acceptor site specificities for three members of UDP-GalNAc:N
      acetylgalactosaminyltransferases by using a synthetic peptide mimicking the
      tandem repeat of MUC5AC.
AB  - The acceptor specificity of three major isoforms of UDP-GalNAc:polypeptide N
      acetylgalactosaminyltranferases (murine recombinant proteins GaNTase-T1, -T2 and 
      T3) was investigated using the synthetic peptide (GTTPSPVPTTSTTSAP) containing
      clusters of threonine residues mimicking the mucin tandem repeat unit of MUC5AC.
      The O-glycosylated products obtained after in vitro reactions were fractionated
      by capillary electrophoresis and the purified glycopeptides were characterized by
      MALDI mass spectrometry (number of O-GalNAc residues) and by Edman degradation
      (site location). A maximum of three GalNAc residues was transferred into the
      MUC5AC motif peptide and the preferential order of incorporation for each GaNTase
      isoform was determined. Our results suggest that clusters of threonine appear to
      be essential for site recognition of peptide backbone by the ubiquitous GaNTases
      and also support the notion that the different GaNTase isoforms with varying
      substrate specificities are involved in a hierarchical order of O-glycosylation
      processing of the mucin-type O-glycoproteins.

PMID- 11448679
TI  - Structure of a cell wall polysaccharide isolated from Hypocrea gelatinosa.
AB  - The structure of a polysaccharide isolated from the cell wall of Hypocrea
      gelatinosa has been investigated by means of chemical analyses and 1D and 2D NMR
      spectroscopy. The polysacharide has an irregular structure, idealized as follows:
      [carbohydrate structure in text].

PMID- 11448680
TI  - Structural studies of the O-polysaccharide from the Escherichia coli O77
      lipopolysaccharide.
AB  - The structure of the O-antigen polysaccharide (PS) from Escherichia coli O77 has
      been determined. Sugar and methylation analysis together with 1H and 13C NMR
      spectroscopy were the main methods used. The PS is composed of tetrasaccharide
      repeating units with the following structure:-->2)-alpha-D-Manp-(1-->2)-beta-D
      Manp-(1-->3)-alpha-D-GlcpNAc-(1-->6)-alpha-D-Manp-(1-->

PMID- 11448682
TI  - Formation and structure of a complex of sucrose with
      cobalt(III)bis(phenanthroline).
AB  - Sucrose forms a dicationic complex with cobalt(III)bis(phenanthroline) which can
      be isolated as the sparingly water-soluble triiodide salt or the water-soluble
      chloride. The circular dichroism (CD) spectrum demonstrates the Delta
      configuration at Co(III) and the presence of two phenanthroline and one sucrose
      residues in the complex. The O-2(g)--O-1(f) distance in crystalline sucrose
      permits strain-free coordination of these centers with Co(III) and in the complex
      the H-1,1'(f) singlet of sucrose separates into a pair of doublets. The 1H NMR
      spectrum in DMSO-d(6) shows that OH-2(g) is deprotonated and the signal of OH
      1(f) is shifted strongly downfield by complexation with Co(III). Coordination
      involving glucose and fructose residues is consistent with neither alpha-methyl
      glucoside nor fructofuranose forming mixed complexes with phenanthroline.
      Structure simulation with the semi-empirical PM3(tm) basis set indicates that
      complexation by O-2(g) and OH-1(f) can give a Delta-complex with little
      structural distortion, whereas in hypothetical Lambda-complexes there is
      distortion of the sucrose residue. Observation of an NOE involving the sucrose
      and phenanthroline residues supports the postulated structure of the Delta
      complex.

PMID- 11448683
TI  - Synthesis of derivatives of C-nucleoside analogues using 'push-pull'
      functionalized monosaccharides.
AB  - 7-Deoxy-1,2:3,4-di-O-isopropylidene-alpha-D-galacto-heptopyranos-6-ulose (1)
      reacted with carbon disulphide and methyl iodide in the presence of a base to
      furnish 7,8-dideoxy-1,2:3,4-di-O-isopropylidene-8,8-[bis(methylthio)]-alpha-D
      galacto-oct-7-enopyranos-6-ulose (2). This 'push-pull' activated unsaturated
      monosaccharide underwent a ring closure reaction with hydrazine hydrate to give
      the 'inversed' C-nucleoside analogue 3. Compound 1 and malononitrile yielded the
      7-cyano-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-6-methyl-alpha-D-galacto-oct-6
      enopyranurononitrile (4). Treatment of 4 with carbon disulphide and methyl iodide
      in the presence of a base afforded the sugar 'push-pull' butadiene 5 which was
      transformed into the pyridine nucleoside analogue 6.

PMID- 11448684
TI  - Synthesis of lipid A type pyran carboxylic acids with ether chains and their
      biological activities.
AB  - Synthesis of lipid A type pyran carboxylic acids having ether chains at both the
      C-3' and C-4 positions and their bioactivities toward human U937 cells are
      described.

PMID- 11448685
TI  - Origin and significance of the production of carbon dioxide during the
      ozonization of 13C-labeled D-glucose at different pH values.
AB  - [1-(13)C], [2-(13)C] and [6-(13)C] D-glucose were, respectively, ozonized in a
      semi-batch reactor in acidic and basic conditions. The composition of the gas
      phase was evaluated by on-line mass spectrometry measurements. The quantitative
      and isotopic analyses of the carbon dioxide formed during ozonization are
      presented and discussed. The data, correlated with previous literature results,
      clearly show that at pH 2.5 the production of carbon dioxide from C-6 and C-1
      carbon atoms is nearly equivalent. Conversely, at higher pH values, CO(2) is
      released with a greater selectivity from the reducing end. The importance of the
      decarboxylation reaction in the formation of by-products with fewer than six
      carbon atoms is also demonstrated.

PMID- 11448686
TI  - Structure of the acidic O-specific polysaccharide from Proteus vulgaris O39
      containing 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-non-2-ulosonic
      acid.
AB  - The O-specific polysaccharide of Proteus vulgaris O39 was found to contain a new
      acidic component of Proteus lipopolysaccharides, 5,7-diacetamido-3,5,7,9
      tetradeoxy-L-glycero-L-manno-non-2-ulosonic acid (di-N-acetylpseudaminic acid,
      Pse5Ac7Ac). The following structure of the polysaccharide was determined by NMR
      spectroscopy, including 2D 1H,(1)H COSY, TOCSY, ROESY, and 1H,(13)C HMQC
      experiments, along with selective cleavage of the polysaccharide by solvolysis
      with anhydrous trifluoromethanesulfonic (triflic) acid: -->8)-beta-Psep5Ac7Ac-(2-
      >3)-alpha-L-FucpNAc-(1-->3)-alpha-D-GlcpNAc-(1--> The structure established is
      unique among the O-specific polysaccharides, which is in accordance with
      classification of the strain studied into a separate Proteus serogroup.

PMID- 11448687
TI  - X-ray structure of beta-cyclodextrin-2,7-dihydroxy-naphthalene.4.6 H(2)O: an
      unusually distorted macrocycle.
AB  - The inclusion complex beta-cyclodextrin.2,7-dihydroxynaphthalene.4.6 H(2)O
      crystallized in the monoclinic space group P2(1), with a=14.082(3), b=19.079(4),
      c=12.417(3) A, beta=109.28(3) degrees, V=3149.0(11) A(3), and Z=2. An X-ray study
      performed at room temperature shows that the crystal packing is of the
      herringbone type with one 2,7-dihydroxynaphthalene included completely in the
      beta-CD cavity, its long axis being oriented along the beta-CD molecular axis,
      and 4.6 water molecules are placed in the interstitial space. The beta-CD
      macrocycle is elliptically distorted, and the guest molecule is held in the
      hydrophobic beta-CD cavity by C-H...O and C-H...pi interactions.

PMID- 11448688
TI  - Crystal structure of N-(tri-O-acetyl-alpha-D-xylopyranosyl)pyridinium bromide.
AB  - The structure of N-(2,3,4-tri-O-acetyl-alpha-D-xylopyranosyl)pyridinium bromide
      was determined by X-ray crystallography and 1H NMR spectroscopy. Two
      xylopyranosyl moieties crystallize with three water molecules and there is a
      novel pattern of Br(-) and H(2)O contacts. Both xylopyranosyl rings in the
      asymmetric unit have the 1C(4) conformation, with all three axial O-Ac groups.

PMID- 11448689
TI  - Effects of cyclic changes in muscle length on force production in in-situ cat
      soleus.
AB  - Muscle shortening and stretch are associated with force depression and force
      enhancement, respectively. Previously, we have investigated the effect of
      combined dynamic contractions (i.e. a single shortening-stretch and stretch
      shortening cycle) on force production (Herzog and Leonard, 2000). In order to
      investigate the relationship between force depression and force enhancement
      systematically, we studied the effects of a single as well as multiple stretch
      shortening and shortening-stretch cycles on the ascending limb of the force
      length relationship. Furthermore, by systematically varying the speed and
      magnitude of stretch preceding shortening and the speed and magnitude of
      shortening preceding stretch, we investigated the influence of these varying
      contractile conditions on force depression and force enhancement, respectively.
      Test contractions were performed on cat soleus (n=6) by electrical stimulation
      using four conceptually different protocols containing a single or repeated
      stretch-shortening and shortening-stretch cycles. The results of this study
      showed that: (1) force depression was not influenced by stretch preceding
      shortening independent of the speed and amount of stretch; (2) force enhancement
      was influenced in a dose-dependent manner by the amount of shortening preceding
      stretch but was not affected by the speed of shortening; (3) repeated stretch
      shortening (shortening-stretch) cycles showed cumulative effects; (4) the number
      of shortening steps over a given distance did not influence the amount of force
      depression. The findings of this study support the idea that the mechanism of
      force depression associated with muscle shortening is different from that of
      force enhancement associated with muscle stretch. Furthermore, they support and
      extend our previous findings that stretch-shortening and shortening-stretch
      cycles are not commutative.

PMID- 11448690
TI  - Loads on an internal spinal fixation device during sitting.
AB  - Sitting is often assumed to involve high loads on the spine as well as on
      implants for stabilising the spine. Loads on internal spinal fixation devices
      were therefore measured in ten patients sitting on several types of seats,
      including a stool, a stool with a padded wedge, a chair, a physiotherapy ball, a
      knee-stool, and a bench. The patients also successively sat relaxed and erect on
      a stool. In addition, six of them sat on a special chair allowing different
      inclinations of the backrest. Implant loads were also measured for standing up
      and sitting down. There were only minor differences in fixator loads for sitting
      on the different types of seats. Sitting erect caused an average of 11% higher
      implant loads than sitting relaxed. Implant loads decreased with increasing
      inclination of the upper body while sitting on a chair with an adjustable
      backrest. Implant loads were about 27% higher for standing up and sitting down
      than for sitting.

PMID- 11448691
TI  - A finite element analysis of hollow stemmed hip prostheses as a means of reducing
      stress shielding of the femur.
AB  - Stress shielding of the femur is known to be a principal factor in aseptic
      loosening of hip replacements. This paper considers the use of a hollow stemmed
      hip implant for reducing the effects of stress shielding, while maintaining
      acceptably low levels of stress in the cement. Using finite element modelling,
      the stresses in the proximal femur using different shapes of hollow stem were
      compared with those produced using comparable sizes of solid stem with different
      values of elastic modulus. A reduction in stress shielding could be achieved with
      a hollow stem. A cylindrical hollow stem design was then optimised in order to
      control the maximum allowable stress in the cement, the minimum allowable
      stresses in the bone, and a combination of the two. The resulting stems achieved
      an increase in proximal bone stress of about 15% for the first case and 32% for a
      model using high strength cement, compared with solid stems of the same nominal
      outside diameter. The gains of these theoretically optimised designs dropped off
      rapidly further down the stem. Linearly tapered hollow stems reached a 22% gain,
      which could be a good compromise between acceptable cement stresses and ease of
      manufacture.

PMID- 11448692
TI  - Experimental investigation of failure load and fracture patterns of C2 (axis).
AB  - The injury mechanism and magnitude of failure load of C2 fractures are important
      in the clinical treatment of its fixation. The magnitudes of the failure load of
      C2 and the mechanism of injury in vivo are uncertain. Accordingly, nine C2
      vertebrae obtained from cadaver spines, ranging in age from 51 to 80 years, were
      used for the study. Special restraint conditions were applied to yield specific
      fracture of C2. With the posterior element potted postero-anteriorly up to one
      quarter of the inferior facet, posterior shear force ranging from 840 to 1220N
      was required to cause fracture across the pars interarticularis. For odontoid
      fracture study, a special rig was fabricated to encapsulate the body of C2 in a
      cell using ISOPON, and a thin layer of ISOPON sandwiched between the inferior
      facets and two lateral plates. The assembled rig permits slight sagittal movement
      of C2 about the cup lateral pivot supports. Failure load of between 900 and 1500N
      was recorded for odontoid fracture. These values are in agreement with published
      data. The experiment carried out under these two different restraint conditions
      had specifically resulted in different fractures of C2. In reality, depending on
      factors such as the inclination of this force vector applied to the head, the
      precise posture at the time of trauma, the spinal geometry, and the physical
      properties, different types of fracture patterns of C2 may be produced. This
      additional data will be useful in the biomechanical study of C2 vertebra using
      analytical approaches, and in surgical anterior/posterior fixation using screws.

PMID- 11448693
TI  - The effect of design variables of condylar total knees on the joint forces in
      step climbing based on a computer model.
AB  - The ability to climb a steep step or rise from a low chair after total knee
      replacement may be enhanced if the required force in the quadriceps muscle is
      reduced. This can potentially be achieved if the total knee produces a large
      lever arm measured from the femoral-tibial contact point to the patellar
      ligament. A reduced quadriceps force would also reduce the patello-femoral force
      and the femoral-tibial contact force. The contact point location is likely to be
      a function of the geometry of the femoral and tibial components in the sagittal
      plane, including the relative distal and posterior radii of the femoral profile,
      the location of the bottom-of-the-dish of the tibial surface, the radius of the
      tibial surface, and the presence or absence of the posterior cruciate ligament. A
      three-dimensional model of the knee was developed including the quadriceps and
      various ligaments. In the study, the motion was confined to flexion extension and
      displacement in the sagittal plane. The quadriceps was assumed to be the only
      muscle acting. A standard software package (Pro/Mechanica) was used for the
      analysis. For a femoral component with a smaller distal radius, there was 12%
      reduction in the quadriceps muscle force and up to 11% reduction in the patello
      femoral force from about 100 up to 60 degrees flexion. However, apart from that,
      there were less than 10% differences in all the forces as a function of all of
      the design variables studied. This was attributed to the relatively small changes
      in the lever arm of the patella tendon, since the tendon moves in an anterior
      posterior direction along with the femur. An additional factor explaining the
      results was the change in the anterior-posterior contact point as controlled by
      the forces in the patella tendon and in the soft tissues. The results imply that
      for a standard condylar replacement knee, the muscle and contact forces are not
      greatly affected by the geometrical design variables.

PMID- 11448694
TI  - In vitro diameter response of rat femoral artery to flow in the presence and
      absence of endothelium.
AB  - We have examined the diameter response of rat femoral artery segments in the
      presence and absence of endothelium to changes in flow rate. The segments were
      isolated, mounted on microcannulae, maintained at 37 degrees C, and perfused at
      90 mmHg with Tyrode's solution. The external arterial diameter was measured using
      video-microscopy. The mean control diameter was 741+/-22 microm (mean+/-SEM,n=7).
      The arteries were preconstricted to 75+/-1% of the control diameter with a
      superfusion of 1 microM norepinephrine (NE). Endothelial function was verified by
      perfusion of 1 micro;M acetylcholine (ACh). Two different flow protocols were
      employed: step changes in flow (n=7) and low-frequency sinusoidal flow changes
      (0.01Hz<f<0.05Hz,n=3). The endothelium was then removed by perfusion of the
      artery with 0.3% CHAPS (n=7) and the flow protocol repeated. All arteries
      contracted with increasing flow. For rapid step changes in flow, contractions and
      relaxations were modelled with an exponential fit where characteristic time
      constants were 34+/-2 and 40+/-3s, respectively (functional endothelium) and 35+/
      2 and 37+/-2s, respectively (non-functional endothelium). The time constants in
      the presence and absence of endothelium were not significantly different (paired
      t-test, p>0.05). Sinusoidal flow oscillations resulted in sinusoidal diameter
      oscillations, whose amplitude and phase lag were inversely proportional to the
      frequency of the flow oscillations. A first-order low-pass filter, with a time
      constant of 28+/-3 and 30+/-5s for arteries with and without functional
      endothelium, respectively, was used to describe the relation between oscillatory
      flow and diameter. The response of the rat femoral arteries to changes in flow
      was not found to be different whether the endothelium was intact or removed.

PMID- 11448695
TI  - Constituents and pH changes in protein rich hyaluronan solution affect the
      biotribological properties of artificial articular joints.
AB  - The relationship between the coefficient of friction and pH value or protein
      constituents of lubricating fluid, together with viscosity, were studied within a
      bearing surface model for artificial joint, ultra-high molecular weight
      polyethylene (UHMWPE) against stainless steel (SUS), using a mechanical
      spectrometer. Four lubricants were tested in this study: sodium hyaluronate (HA),
      HA with albumin, HA with gamma-globulin, and HA with (L)alpha-dipalmitoyl
      phosphatidylcholine ((L)alpha-DPPC). The coefficient of friction between UHMWPE
      and SUS in HA with albumin or HA with gamma-globulin varied from 0.035 to 0.070
      depending on angular velocity and pH. The coefficient of friction in HA or HA
      with (L)alpha-DPPC varied from 0.023 to 0.045 depending on angular velocity and
      pH. The variation in pH for HA with albumin had a large effect on the coefficient
      of friction at low range of angular velocity with viscosity independence. The
      variation in pH for HA with gamma-globulin had a large effect on the coefficient
      of friction with viscosity dependence at high angular velocity. The addition of
      (L)alpha-DPPC showed a small effect on the coefficient of friction at low angular
      velocity. This study confirms that the presence of albumin in the lubricant
      promotes pH dependence and viscosity independence of the tribological properties
      at low speed while the presence of globulin promotes pH and viscosity
      independence at low speed and promotes pH and viscosity dependence at high speed
      in the lubrication of UHMWPE against SUS. This study supports the clinical
      hypothesis that the effect of constituents and pH changes in periprosthetic fluid
      for the lubrication is a clue toward resolving many complications after total
      joint replacement.

PMID- 11448696
TI  - Simulated active control produces repeatable motion pathways of the elbow in an
      in vitro testing system.
AB  - The purpose of this study was to determine if the repeatability and pattern of
      elbow kinematics are affected by changing the relative magnitudes of loads
      applied to muscles around the elbow in vitro. In eight cadaveric upper
      extremities, passive and three methods of simulated active elbow flexion were
      tested with the forearm maintained in both pronation and supination. Passive
      flexion involved moving the elbow manually through a full arc of motion.
      Simulated active flexion used a custom designed loading system to generate elbow
      motion by applying loads to various tendons via pneumatic actuators. Three
      different simulated active loading protocols, with loading ratios based on muscle
      activity and physiologic cross-sectional area, were tested. Testing was performed
      initially on an intact elbow, and then an unstable elbow model created by
      transection of the lateral collateral ligament (i.e. the radial and lateral ulnar
      collateral ligaments). An electromagnetic tracking device was used to measure
      rotation of the ulna relative to the humerus. Varus-valgus angulation and
      internal-external rotation were less repeatable during passive flexion than
      simulated active flexion, regardless of the loading ratio used, in both the
      intact (p<0.05) and unstable (p<0.05) elbows. Throughout the arc of flexion, the
      motion pathways were similar for the three simulated active motion protocols
      employed in this study (p>0.05). The pathways followed during passive motion were
      different from those generated with simulated active motion, especially in the
      unstable elbow with the forearm supinated (p<0.001). These results suggest that
      using simulated active motion rather than manual passive motion can improve the
      repeatability of elbow kinematics generated in the laboratory, and that a wide
      range of muscle loading ratios may produce similar kinematic output.

PMID- 11448697
TI  - Numerical and experimental models of post-operative realistic flows in stenosed
      coronary bypasses.
AB  - By means of both experimental and finite element methods, we simulated three
      dimensional unsteady flows through coronary bypass anastomosis. The host artery
      includes a stenosis shape located at two different distances of grafting. The
      inflow rates are issued from in vivo measurements in patients who had undergone
      coronary bypass surgery a few days before. We provide a comparison between
      experimental and numerical velocity profiles coupled with the numerical analysis
      of spatial and temporal wall shear stress evolution. The interaction between the
      graft and coronary flows has been demonstrated. The phase inflow difference can
      partly be responsible for specific flow phenomena: jet deflection towards a
      preferential wall or feedback phenomenon that causes the flapping of the post
      stenotic jet during the cardiac cycle. In conclusion, we showed the sensitivity
      of these typical flows to distance of grafting, inflows waveforms but also to
      their phase difference.

PMID- 11448698
TI  - Mechanical properties of coronary stents determined by using finite element
      analysis.
AB  - The mechanical function of a stent deployed in a damaged artery is to provide a
      metallic tubular mesh structure. The purpose of this study was to determine the
      exact mechanical characteristics of stents. In order to achieve this, we have
      used finite-element analysis to model two different type of stents: tubular
      stents (TS) and coil stents (CS). The two stents chosen for this modeling present
      the most extreme mechanical characteristics of the respective types. Seven
      mechanical properties were studied by mathematical modeling with determination
      of: (1) stent deployment pressure, (2) the intrinsic elastic recoil of the
      material used, (3) the resistance of the stent to external compressive forces,
      (4) the stent foreshortening, (5) the stent coverage area, (6) the stent
      flexibility, and (7) the stress maps. The pressure required for deployment of CS
      was significantly lower than that required for TS, over 2.8 times greater
      pressure was required for the tubular model. The elastic recoil of TS is higher
      than CS (5.4% and 2.6%, respectively). TS could be deformed by 10% at compressive
      pressures of between 0.7 and 1.3 atm whereas CS was only deformed at 0.2 and 0.7
      atm. The degree of shortening observed increases with deployment diameter for TS.
      CS lengthen during deployment. The metal coverage area is two times greater for
      TS than for CS. The ratio between the stiffness of TS and that of CS varies from
      2060 to 2858 depending on the direction in which the force is applied. TS are
      very rigid and CS are significantly more flexible. Stress mapping shows stress to
      be localized at link nodes. This series of finite-element analyses illustrates
      and quantifies the main mechanical characteristics of two different commonly used
      stents. In interventional cardiology, we need to understand their mechanisms of
      implantation and action.

PMID- 11448699
TI  - Predictive algorithms for neuromuscular control of human locomotion.
AB  - The problem of quantifying muscular activity of the human body can be formulated
      as an optimal control problem. The current methods used with large-scale
      biomechanical systems are non-derivative techniques. These methods are costly, as
      they require numerous integrations of the equations of motion. Additionally, the
      convergence is slow, making them impractical for use with large systems. We apply
      an efficient numerical algorithm to the biomechanical optimal control problem.
      Using direct collocation with a trapezoidal discretization, the equations of
      motion are converted into a set of algebraic constraint equations. An augmented
      Lagrangian formulation is used for the optimization problem to handle both
      equality and inequality constraints. The resulting min-max problem is solved with
      a generalized Newton method. In contrast to the prevalent optimal control
      implementations, we calculate analytical first- and second-derivative information
      and obtain local quadratic convergence. To demonstrate the efficacy of the
      method, we solve a steady-state pedaling problem with 7 segments and 18
      independent muscle groups. The computed muscle activations compare well with
      experimental EMG data. The computational effort is significantly reduced and
      solution times are a fraction of those of the non-derivative techniques.

PMID- 11448700
TI  - The force resulting from the action of mono- and biarticular muscles in a limb.
AB  - Human and animal limbs can be modelled as a chain of segments connected at
      joints. For a static limb, the force exerted at the endpoint due to the force of
      a single muscle has been calculated. It turns out that there are marked
      differences in the action of mono- vs. biarticular muscles. Monoarticular muscles
      produce an endpoint force that is directed in the lengthwise direction of the
      limb, i.e. in the direction of one of the segments. The force from biarticular
      muscles can have a marked transverse component. The 'principal direction' of this
      endpoint force is also the movement direction of the endpoint which is the most
      favourable for the muscle to do work. The reasoning presented can explain e.g.
      the differences in the activity of mono- and biarticular muscles in cycling.

PMID- 11448701
TI  - Animation of in vitro biomechanical tests.
AB  - Interdisciplinary communication of three-dimensional kinematic data arising from
      in vitro biomechanical tests is challenging. Complex kinematic representations
      such as the helical axes of motion (HAM) add to the challenge. The difficulty
      increases further when other quantities (i.e. load or tissue strain data) are
      combined with the kinematic data. The objectives of this study were to develop a
      method to graphically replay and animate in vitro biomechanical tests including
      HAM data. This will allow intuitive interpretation of kinematic and other data
      independent of the viewer's area of expertise. The value of this method was
      verified with a biomechanical test investigating load-sharing of the cervical
      spine. Three 3.0 mm aluminium spheres were glued to each of the two vertebrae
      from a C2-3 segment of a human cervical spine. Before the biomechanical tests, CT
      scans were made of the specimen (slice thickness=1.0 mm and slice spacing=1.5
      mm). The specimens were subjected to right axial torsion moments (2.0 Nm). Strain
      rosettes mounted to the anterior surface of the C3 vertebral body and bilaterally
      beneath the facet joints on C3 were used to estimate the force flow through the
      specimen. The locations of the aluminium spheres were digitised using a space
      pointer and the motion analysis system. Kinematics were measured using an
      optoelectronic motion analysis system. HAMs were calculated to describe the
      specimen kinematics. The digitised aluminium sphere locations were used to match
      the CT and biomechanical test data (RMS errors between the CT and experimental
      points were less than 1.0 mm). The biomechanical tests were "replayed" by
      animating reconstructed CT models in accordance with the recorded experimental
      kinematics, using custom software. The animated test replays allowed intuitive
      analysis of the kinematic data in relation to the strain data. This technique
      improves the ability of experts from disparate backgrounds to interpret and
      discuss this type of biomechanical data.

PMID- 11448702
TI  - The effect of finger extensor mechanism on the flexor force during isometric
      tasks.
AB  - The role of the intrinsic finger flexor muscles was investigated during finger
      flexion tasks. A suspension system was used to measure isometric finger forces
      when the point of force application varied along fingers in a distal-proximal
      direction. Two biomechanical models, with consideration of extensor mechanism
      Extensor Mechanism Model (EMM) and without consideration of extensor mechanism
      Flexor Model (FM), were used to calculate forces of extrinsic and intrinsic
      finger flexors. When the point of force application was at the distal phalanx,
      the extrinsic flexor muscles flexor digitorum profundus, FDP, and flexor
      digitorum superficialis, FDS, accounted for over 80% of the summed force of all
      flexors, and therefore were the major contributors to the joint flexion at the
      distal interphalangeal (DIP), proximal interphalangeal (PIP), and
      metacarpophalangeal (MCP) joints. When the point of force application was at the
      DIP joint, the FDS accounted for more than 70% of the total force of all flexors,
      and was the major contributor to the PIP and MCP joint flexion. When the force of
      application was at the PIP joint, the intrinsic muscle group was the major
      contributor for MCP flexion, accounting for more than 70% of the combined force
      of all flexors. The results suggest that the effects of the extensor mechanism on
      the flexors are relatively small when the location of force application is distal
      to the PIP joint. When the external force is applied proximally to the PIP joint,
      the extensor mechanism has large influence on force production of all flexors.
      The current study provides an experimental protocol and biomechanical models that
      allow estimation of the effects of extensor mechanism on both the extrinsic and
      intrinsic flexors in various loading conditions, as well as differentiating the
      contribution of the intrinsic and extrinsic finger flexors during isometric
      flexion.

PMID- 11448703
TI  - Psychological influences on acceptance of postsurgical treatment in cancer
      patients.
AB  - OBJECTIVE: Many cancer patients fail to complete treatment for reasons that are
      unclear in previous research which, nevertheless, suggested hypotheses for this
      study about the characteristics of the patients and their consultations. METHOD:
      158 adults with breast cancer or other cancers who had been chosen for
      postsurgical treatment in the Lister Hospital or the Mount Vernon Hospital had
      completed published questionnaires to assess either (n=74) personal attributes or
      circumstances viz. locus of health control, health habits, support, affiliative
      drive, anxiety, depression, or (n=84) their attitudes to cancer or their
      consultations, viz. the Mental Attitudes to Cancer Scales, Trust in Physicians,
      Perceived Empathy, and Satisfaction With Recent and Diagnostic Consultations.
      RESULTS: 32% then failed to complete treatment. In logistic multiple regression
      analyses, only diagnosis (P=.0001), gender (P=.005), and treatment center
      (P=.0002) predicted this although the effect of gender was not significant among
      patients without breast cancer. Among the patients without breast cancer intended
      for the Mount Vernon Hospital, a National Cancer Centre, fewer completed
      treatment than those did not complete. CONCLUSION: The breast cancer patients,
      unlike women with other cancers, and patients referred to the local hospital
      rather than the regional cancer center, were more likely to complete treatment.
      Thus, uptake of treatment may be favored by accessibility and familiarity of its
      source and by the unique impact in women of breast cancer and the wider public
      attention given to that illness. Research on patients' expectations, fears, and
      corresponding experiences of treatment, rather than personal attributes, should
      clarify failure to complete cancer treatment especially in patients without
      breast pathology.

PMID- 11448704
TI  - Medically unexplained symptoms: an epidemiological study in seven specialities.
AB  - OBJECTIVES: This study aimed to estimate the prevalence and risk factors for
      medically unexplained symptoms across a variety of specialities. METHODS: A cross
      sectional survey was conducted at two general hospitals in southeast London
      between 1995 and 1997. Eight hundred and ninety consecutive new patients from
      seven outpatient clinics were included. Demographic and clinical characteristic
      variables were assessed. RESULTS: Five hundred eighty-two (65%) of the subjects
      surveyed returned completed questionnaires. A final diagnosis was available in
      550 (62%). Two hundred twenty-eight (52%) fulfilled criteria for medically
      unexplained symptoms. The highest prevalence was in the gynecology clinic (66%).
      After adjustment for confounders, medically unexplained symptoms were associated
      with being female, younger, and currently employed. Psychiatric morbidity per se
      was not associated with the presence of medically unexplained symptoms, but was
      more likely in those complaining of multiple symptoms. Those with medically
      unexplained symptoms were less disabled, but more likely to use alternative
      treatment in comparison with those whose symptoms were medically explained.
      Patients with medically unexplained symptoms were more likely to attribute their
      illness to physical causes as opposed to lifestyle factors. CONCLUSIONS:
      Medically unexplained symptoms are common across general/internal medicine and
      represent the most common diagnosis in some specialities. Medical behavior,
      training, and management need to take this into account.

PMID- 11448705
TI  - Psychological treatment for recurrent symptoms of colds and flu in children.
AB  - The effect of stress management and relaxation with guided imagery on upper
      respiratory tract infections (URTIs) was investigated in 45 children with a
      history of 10 or more infections in the past year. To investigate the influence
      of psychological treatment on mucosal immunity, secretory immunoglobulin A (sIgA)
      was measured before and during treatment. The number of symptomatic episodes
      during 13 weeks of monitoring was similar in treatment and waitlist conditions;
      however, episodes were shorter in stress management and guided imagery conditions
      than in the waitlist condition. Levels of sIgA increased toward the end of
      treatment. These findings were confirmed in a replication study. In addition,
      symptom reduction and improvements in psychological state persisted at 1-year
      follow-up. The findings suggest that psychological treatment interrupts a chronic
      illness cycle in children with symptoms of recurrent URTI.

PMID- 11448706
TI  - Validation of the Chinese-version MPSS-R for occupational stress among emergency
      nurses.
AB  - The aim of this study was to examine the reliability and validity of a Chinese
      version stress instrument among emergency nurses. The study sample comprised of
      113 nurses whose age ranged from 21 to 47 years old. The Chinese version of
      Medical Personnel Stress Survey (MPSS-R) was answered in 1996 through self
      administered questionnaires. The instrument demonstrated excellent convergent and
      discriminant validity. Cronbach's alpha (reliability) coefficients ranged from.57
      to.77. Factorial analysis yielded four principal components, corresponding to job
      dissatisfaction, team relationship, organization support, and somatic distress.
      Validation by independent variable was also consistent with theory. Thus, the
      Chinese-version MPSS-R retained excellent psychometric properties when used in an
      emergency nurses group.

PMID- 11448707
TI  - Feeling your body or feeling badly: evidence for the limited validity of the
      Somatosensory Amplification Scale as an index of somatic sensitivity.
AB  - OBJECTIVE: The Somatosensory Amplification Scale (SSAS) purports to measure the
      extent to which individuals are sensitive to their bodies. The present study
      examined the psychometric properties of the SSAS in two studies with university
      students. METHODS: Participants completed the SSAS, various cross-sectional
      measures of somatic and psychological distress, longitudinal measures of somatic
      symptoms, daily hassles and mood, and participated in a heartbeat detection task
      (Study 2 only). RESULTS: The SSAS was correlated with cross-sectional measures of
      somatic symptom reporting, but not with somatic symptoms reported on a daily
      basis nor with an index of interoceptive sensitivity. The SSAS was also
      correlated with several indices of general distress including anxious and
      depressive symptoms, daily hassles, and negative emotionality. CONCLUSION: Taken
      together, the results suggest that the SSAS is more likely an index of negative
      emotionality and general distress than a valid measure of somatic sensitivity per
      se.

PMID- 11448708
TI  - Thoroughly modern worries: the relationship of worries about modernity to
      reported symptoms, health and medical care utilization.
AB  - OBJECTIVE: There is now greater public concern about how features of modern life
      pose threats to personal health. In two studies, we investigated the relationship
      between individuals' worries about modernity affecting health to symptom reports,
      perceptions of health and health care utilization. METHODS: In the first study,
      526 University students completed a questionnaire measuring modern health worries
      (MHW), symptom reports and health perceptions. A second study utilized an
      existing national survey database of 7869 New Zealanders. Part of the survey
      examined people's concerns of modernity affecting their health in the past 12
      months, as well as the use of conventional medical and alternative health care.
      RESULTS: We found concerns about modernity affecting health were made up of four
      major components: environmental pollution, toxic interventions, tainted food and
      radiation. MHW were significantly associated with somatic complaints and ratings
      of the importance of health to the individual. We also found individuals with
      high levels of MHW had a higher rate of food intolerance and chronic fatigue
      syndrome (CFS). In the second study, we found MHW to be associated with medical
      care utilization, particularly of alternative health practitioners. CONCLUSIONS:
      The results of these studies suggest concerns about modernity do cause changes in
      the way individuals interpret somatic information and may play a role in
      undermining perceptions of health. The area of MHW is worthy of study and may
      hold importance for understanding aspects of functional disorders.

PMID- 11448709
TI  - The influence of HEPES on light responses of rabbit horizontal cells.
AB  - HEPES-buffered solutions, mostly used in studies of isolated cells, and
      bicarbonate-buffered solutions, mostly used in studies of isolated retinal
      tissues, have both been used to superfuse an isolated rabbit retina preparation.
      The responses of horizontal cells (HCs) to light, detected by intracellular
      microelectrodes filled with Lucifer Yellow, were recorded. Buffering of the
      superfusate with 100% HEPES completely, but reversibly, abolished the responses
      of A-type HCs, and is not, therefore, suitable for studies on isolated rabbit
      retinas. The responses remained when buffering was partially with HEPES and
      partially with bicarbonate, but were changed: in A-type HCs the overshoot was
      reduced and the afterpotential was increased. The overshoot may be caused by
      feedback of HCs on the cones and might be dependent on pHi at the synaptic
      structure between HCs and photoreceptors.

PMID- 11448710
TI  - Evaluation of different recording parameters to establish a standard for flash
      electroretinography in rodents.
AB  - Different electrodes and stimulus protocols commonly used for electroretinography
      in rodent eyes were compared for convenience of use, degree of damage to corneal
      epithelium, and for magnitude of amplitude, reproducibility, left versus right
      eye accuracy, and reliability of recorded parameters of the flash
      electroretinogram (ERG). Adult C57BL/6 pigmented mice and albino Wistar rats were
      used to determine scotopic ERGs in response to Ganzfeld or strobe-light
      stimulation and light-adapted (photopic) ERGs recorded from both eyes at the same
      time. Test-retest data were used for statistical analyses to compare a monopolar
      gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride
      electrode (CSCE), a DTL fiber electrode (DTLE), and a circular stainless steel
      wire electrode (SSE). Corneas were evaluated for abrasion after ERG recordings
      using fluorescein staining and also for the time taken, ease of insertion, and re
      insertions required for the different electrodes. Compared to CSCE, DTLE, and
      SSE, the ERG potentials recorded by CLE had significantly larger scotopic
      amplitudes and oscillatory potentials under strobe or Ganzfeld stimulation and
      for light-adapted ERG b-wave amplitudes in both mice and rats. In analyzing test
      retest data of scotopic ERG a-wave and b-wave amplitudes, the intraclass
      correlation coefficient showed the best agreement for the CLE (range 0.61-0.94)
      compared to the SSE (0.13-0.77), DTLE (0.02-0.69), and CSCE (0.12-0.51). In mice
      and rats, logistic regression analyses revealed significant correlations for
      amplitudes of most scotopic ERG parameters between contralateral eyes obtained
      with CLE and for some ERG components recorded by SSE. When comparing ERG
      amplitudes for stimulation by strobe or Ganzfeld, the difference was least with
      the CLE compared to DTLE, CSCE, or SSE. The time taken to insert the four
      different electrodes was greatest for the CLE in both mice and rats. The extent
      of corneal abrasion resulting from electrode use in mice was largest for the SSE
      followed by the CLE. However, in rats there was almost no corneal damage after
      ERG recordings with the CLE. Because of the stability of eye contact, the CLE
      allows ERGs to be determined over a longer recording session. Recording of
      scotopic and photopic (light-adapted) ERGs in rodents with monopolar gold-wire
      contact lens electrodes provides greater amplitudes and higher reproducibility
      when compared to other commonly used corneal electrodes. These electrodes are
      significantly better overall than others that were evaluated and should be
      considered for a standard protocol to monitor retinal function in rodent eyes.

PMID- 11448711
TI  - Directional tuning of human motion adaptation as reflected by the motion VEP.
AB  - Motion onset evoked visual potentials are dominated by a negativity (N2) at
      occipital electrodes and a positivity (P2) at the vertex. The degree of true
      motion processing reflected by N2 and P2 was estimated from the direction
      specificity of motion adaptation. Adapting stimuli moved to the right and test
      stimuli (random dot patterns of 26 degrees diameter; 10% contrast; 10.5 degrees
      /s velocity) moved in one of eight directions, which differed by 45 degrees. VEPs
      were recorded from occipito/temporal and central sites in eight subjects. Two
      adaptation effects were observed for N2 (P<0.01): a global amplitude reduction by
      47% and a direction-specific reduction by a further 28%. For P2, only the global
      effect (54%; P<0.01) was observed. The global adaptation effect could also be
      induced by pattern reversal and pattern-onset adaptation, i.e. stimuli containing
      ambiguous or very little motion energy, respectively. We conclude that at least
      28% of the N2 amplitude reflects the activity of direction-specific elements,
      whereas P2 does not at all.

PMID- 11448712
TI  - Direction-specific changes of sensitivity after brief apparent motion stimuli.
AB  - Direction-specific losses in sensitivity were found for a test grating which was
      superimposed on a stationary contrast pedestal and which moved either in the same
      or opposite direction as a prior biasing stimulus. Three types of biasing stimuli
      were employed: a grating swept through 270 degrees in 45 degrees steps, a single
      90 degrees step of a grating, and a single 90 degrees step of a grating which
      contained a blank IFI and whose perceived direction was reversed. For the biasing
      sweep and the single 90 degrees step, the response of directionally selective
      mechanisms (directional motion energy) is greatest for the direction which
      corresponds to the actual physical displacement of the stimulus. For the biasing
      step with an IFI, the response is maximum for the opposite direction. For all
      three types of biasing stimuli, directional sensitivity for a test stimulus was
      reduced most when it moved in the biasing direction, i.e. the direction which
      produced the strongest signal in directionally selective mechanisms. Unlike the
      effects of the same types of biasing stimuli on the perceived direction of a
      suprathreshold 180 degrees step of a grating [Pinkus, A., & Pantle, A. (1997).
      Probing motion signals with a priming paradigm. Vision Research, 37, 541-52;
      Pantle, A., Gallogly, D.P., & Piehler, O.C. (2000). Direction biasing by brief
      apparent motion stimuli. Vision Research, 40, 1979-91], all the direction
      specific losses of sensitivity can be explained by changes in the response
      characteristics of directionally selective mechanisms.

PMID- 11448713
TI  - Lines and dots: characteristics of the motion integration process.
AB  - Local motion detectors can only provide the velocity component perpendicular to a
      moving line that crosses their receptive field, leading to an ambiguity known as
      the "aperture problem". This problem is solved exactly for rigid objects
      translating in the screen plane via the intersection of constraints (IOC). In
      natural scenes, however, object motions are not restricted to fronto-parallel
      translations, and several objects with distinct motions may be present in the
      visual space. Under these conditions the usual IOC construction is no longer
      valid, which raises questions as its use as a basis for spatial integration and
      selection of motion signals in uniform and non-uniform velocity fields. The
      influence of the motion of random dots on the perceived direction of a horizontal
      line grating was measured, when dots and lines are seen through different
      apertures. The random dots were mapped on a plane that translates in a fronto
      parallel plane (uniform 2D translation) or in depth (3D, corresponding to a non
      uniform projected velocity field, either expanding or contracting). The grating
      was either moving rigidly with the dots or in the opposite direction. Subjects'
      responses show that the direction of line grating movement was reliably
      influenced only in conditions consistent with rigid motion; where there was a
      reliable influence, the perceived direction was consistent with the dot motion
      pattern. This finding points to the existence of a motion-based selection
      mechanism that operates prior to the disambiguation of the line movement
      direction. Disambiguation could occur for both uniform and non-uniform velocity
      fields, even though in the last case none of the individual dots indicated the
      proper direction in 2D velocity space. Finally, the capture by non-uniform motion
      patterns was less robust than that by uniform 2D translations, and could be
      disrupted by manipulations of the shape and size of the apertures.

PMID- 11448714
TI  - Size-based selection in rapid serial visual presentation.
AB  - Several recent studies [Farell, B., & Pelli, D. (1993). Can we attend to large
      and small at the same time? Vision Research, 33, 2757-72; Shih, S., & Sperling,
      G. (1996). Is there feature-based attentional selection in visual search? Journal
      of Experimental Psychology: Human Perception and Performance, 22, 758-79] have
      found that visual selection based on the size of stimuli is impossible when the
      stimuli are presented in rapid succession in overlapping positions (RSVP
      paradigm). In the present study effective size-based selection is demonstrated in
      several conditions with RSVP stimuli. Attention to specific size is highly
      efficient when stimuli are presented in a single location (at fixation point) and
      may be possible also with a few (2-4) locations. When overlapping small and large
      characters are presented without abrupt onsets, then selection by size is
      effective at least over six locations. The results are explained by certain
      mandatory properties of spatial attention.

PMID- 11448715
TI  - Stereoprocessing of cyclopean depth images: horizontally elongated summation
      fields.
AB  - The study evaluated how the detection efficiency varies with the length and width
      of Gabor wavelets of depth ripple in random element patterns. For local (one
      cycle) wavelets, there was no anisotropy with respect to wavelet orientation,
      implying equal efficiency for processing shear versus compression disparities at
      threshold. The processing for larger patterns of depth ripple did not correspond
      to a fixed summation field but varied in size with spatial frequency, and in
      shape with orientation of depth ripples, up to four cycles of a horizontal bar at
      0.5 cy/deg, or 8 degrees of visual angle. The presence of such extended summation
      fields in only one orientation is incompatible with the idea of local attentional
      processing, with a single disparity channel or with an adaptive mechanism that
      could accommodate to any form of disparity image. Thus, these results suggest the
      presence of a multichannel hypercyclopean level of processing specialized for
      horizontal depth contours, whose only disparity information is in their surface
      texture.

PMID- 11448716
TI  - Chameleon eye position obeys Listing's law.
AB  - Listing's law (LL) states that 3D-eye positions lie in a plane, when they are
      described as single-axis rotations from the primary position. This implies that
      the degrees of freedom of eye movements are reduced from three to two. Various
      hypotheses exist, regarding the implementation of LL. These include facilitation
      of binocular vision, optimization of oculomotor control, and mechanical
      constraints in the orbit. We recorded the 3D-eye position during saccadic
      scanning in the chameleon, to investigate whether LL is valid in an animal with
      different anatomical and behavioral characteristics compared to primates. We show
      that in chameleons, the eye position obeys LL with a high precision. Since the
      anatomical arrangement of the orbit in chameleons is very different from that in
      primates, and binocular fused vision is virtually absent, we suggest that in the
      chameleon, LL mainly optimizes oculomotor control.

PMID- 11448717
TI  - Smooth eye movements and spatial localisation.
AB  - We asked subjects to align a target that flashed as their eyes rotated to the
      right in pursuit of a moving ring, with a target that flashed as their eyes
      rotated to the left in pursuit of the ring. Subjects systematically mislocalised
      the targets in the direction of pursuit. When the ring and flashes were the only
      structures that were visible, the alignment error was about 4 cm, corresponding
      to a timing error of about 100 ms. The timing error was independent of the
      position along the ring's path, but did depend to some extent on pursuit
      velocity. Adding a textured background reduced the mislocalisation considerably,
      presumably because it enabled subjects to localise the targets relative to the
      surrounding. There was almost no mislocalisation if the subject was not pursuing
      the ring. It is suggested that the mislocalisation arises because incoming
      retinal signals are combined directly with outgoing oculo-motor commands, with no
      attempt to account for any of the involved neuronal and muscular delays.

PMID- 11448718
TI  - Bubbles: a technique to reveal the use of information in recognition tasks.
AB  - Everyday, people flexibly perform different categorizations of common faces,
      objects and scenes. Intuition and scattered evidence suggest that these
      categorizations require the use of different visual information from the input.
      However, there is no unifying method, based on the categorization performance of
      subjects, that can isolate the information used. To this end, we developed
      Bubbles, a general technique that can assign the credit of human categorization
      performance to specific visual information. To illustrate the technique, we
      applied Bubbles on three categorization tasks (gender, expressive or not and
      identity) on the same set of faces, with human and ideal observers to compare the
      features they used.

PMID- 11448719
TI  - Regularization in a neural model of motion perception.
AB  - Neurons in sensory systems encode and transmit information about attributes of
      the environment. Much of the information transmitted by spiking neurons appears
      to be encoded in the rate at which they fire. This rate necessarily has a
      positive value. In this paper, the implication of this constraint for models of
      motion detection is examined. The detection of image motion is represented
      mathematically as a quadratic programming problem in which variables used to
      represent image speed are restricted to positive values. This novel
      representation requires that additional constraints are introduced to stabilize
      motion computations because quadratic programming problems require a surplus of
      unknowns to code for image speed. Two further constraints are introduced into the
      model to take into account possible cases of image degeneracy. They are based
      upon (i) an a priori preference for small image speeds, and (ii) the assumption
      that image motion parallel to contours of constant intensity for a one
      dimensional signal is zero. The latter assumption is shown to account for
      perceived biases in speed reported for type I plaid patterns [Castet, E. &
      Morgan, M. (1996). Apparent speed of type-I symmetrical plaids. Vision Research
      36, 223-32]. The model suggests that the visual system uses separate constraints
      to stabilize motion computations. One set of constraints arises from the nature
      of the motion detection process itself, while another two constraints take into
      account possible cases of degeneracy where image contrast is low or near zero and
      where the image function is one-dimensional and the aperture problem prevails.

PMID- 11448720
TI  - Contour interaction in amblyopia: scale selection.
AB  - It has been known for some time that visual acuity in amblyopia is higher for
      single letters than for letters in a row (termed crowding). Early work showed
      that this could not be accounted for on the basis of the destructive interaction
      of adjacent contours (termed contour interaction), which was shown to be, in
      resolution units, normal in amblyopia. We have re-examined this issue using a
      letter stimulus that is modulated about a mean light level. This allows an
      examination of the effects of contrast polarity and spatial filtering within the
      contour interaction paradigm. We show that the majority of strabismic amblyopes
      that we investigated exhibit an anomalous contour interaction that, in some
      cases, was dependent on the contrast polarity of the flanking stimuli.
      Furthermore, we show that while amblyopes do select the optimum scale of analysis
      for unflanked stimuli, they do not select the optimum scale of analysis for
      flanked stimuli. For reasons that may have to do with their poorer shape
      discrimination, they select a non-optimal scale to process flanked stimuli.

PMID- 11448721
TI  - Different effects of lorazepam and diazepam on perceptual integration.
AB  - Recent research has established the detrimental effect of lorazepam, a
      benzodiazepine, on both implicit and explicit memory. Furthermore, lorazepam is
      known to affect perceptual integration. Diazepam, on the other hand, though being
      a benzodiazepine too, only impairs explicit memory, leaving implicit memory
      fairly intact. Little is known about the effect of diazepam on perceptual
      integration. The present study aimed at filling in this gap, by comparing the
      effects of lorazepam and diazepam on the detection of discontinuities in random
      shaped outlines. In line with previous findings, the results in a lorazepam
      treated group were quite different from the results in a placebo-treated group.
      The results in a diazepam-treated group were analogous to the results in the
      placebo-treated group and different from the results in the lorazepam-treated
      group. This shows that lorazepam and diazepam differ, not only with respect to
      their effect on implicit memory, but also with respect to their effect on
      perceptual integration. It is argued that this bears important consequences for
      memory research that makes use of a pharmacological dissociation rationale.

PMID- 11448722
TI  - KCNQ potassium channels: physiology, pathophysiology, and pharmacology.
AB  - KCNQ genes encode a growing family of six transmembrane domains, single pore
      loop, K(+) channel alpha-subunits that have a wide range of physiological
      correlates. KCNQ1 (KvLTQ1) is co-assembled with the product of the KCNE1 (minimal
      K(+)-channel protein) gene in the heart to form a cardiac-delayed rectifier-like
      K(+) current. Mutations in this channel can cause one form of inherited long QT
      syndrome (LQT1), as well as being associated with a form of deafness. KCNQ1 can
      also co-assemble with KCNE3, and may be the molecular correlate of the cyclic AMP
      regulated K(+) current present in colonic crypt cells. KCNQ2 and KCNQ3
      heteromultimers are thought to underlie the M-current; mutations in these genes
      may cause an inherited form of juvenile epilepsy. The KCNQ4 gene is thought to
      encode the molecular correlate of the I(K,n) in outer hair cells of the cochlea
      and I(K,L) in Type I hair cells of the vestibular apparatus, mutations in which
      lead to a form of inherited deafness. The recently identified KCNQ5 gene is
      expressed in brain and skeletal muscle, and can co-assemble with KCNQ3,
      suggesting it may also play a role in the M-current heterogeneity. This review
      will set this family of K(+) channels amongst the other known families. It will
      highlight the genes, physiology, pharmacology, and pathophysiology of this
      recently discovered, but important, family of K(+) channels.

PMID- 11448723
TI  - The mechanisms of action of commonly used antiepileptic drugs.
AB  - In the past decade, nine new drugs have been licensed for the treatment of
      epilepsy. With limited clinical experience of these agents, the mechanisms of
      action of antiepileptic drugs may be an important criterion in the selection of
      the most suitable treatment regimens for individual patients. At the cellular
      level, three basic mechanisms are recognised: modulation of voltage-dependent ion
      channels, enhancement of inhibitory neurotransmission, and attenuation of
      excitatory transmission. In this review, we will attempt to introduce the
      concepts of ion channel and neurotransmitter modulation and, thereafter, group
      currently used antiepileptic drugs according to their principal mechanisms of
      action.

PMID- 11448724
TI  - Characterisation of portal hypertension models by microspheres in anaesthetised
      rats: a comparison of liver flow.
AB  - Several portal hypertensive animal models are available and frequently used for
      haemodynamic studies. The portal venous inflows, measured with microspheres in
      pentobarbital anaesthetised rats, are compared here. The partial portal vein
      ligation model is characterised by a high portal venous inflow, together with
      extensive portal systemic shunting, at the cost of portal sinusoidal flow. In
      carbon tetrachloride-induced micronodular cirrhosis, portal sinusoidal flow,
      which reaches liver parenchyma, is high, and this is more pronounced in the
      presence of ascites. In bile duct ligation and excision-induced cirrhosis, an
      increase in liver weight was not equally followed by an increase in portal
      sinusoidal flow, pointing to a relatively underperfused liver.

PMID- 11448725
TI  - The endocannabinoid nervous system: unique opportunities for therapeutic
      intervention.
AB  - The active principle in marijuana, Delta(9)-tetrahydrocannabinol (THC), has been
      shown to have wide therapeutic application for a number of important medical
      conditions, including pain, anxiety, glaucoma, nausea, emesis, muscle spasms, and
      wasting diseases. Delta(9)-THC binds to and activates two known cannabinoid
      receptors found in mammalian tissue, CB1 and CB2. The development of cannabinoid
      based therapeutics has focused predominantly on the CB1 receptor, based on its
      predominant and abundant localization in the CNS. Like most of the known
      cannabinoid agonists, Delta(9)-THC is lipophilic and relatively nonselective for
      both receptor subtypes. Clinical studies show that nonselective cannabinoid
      agonists are relatively safe and provide therapeutic efficacy, but that they also
      induce psychotropic side effects. Recent studies of the biosynthesis, release,
      transport, and disposition of anandamide are beginning to provide an
      understanding of the role of lipid transmitters in the CNS. This review attempts
      to link current understanding of the basic biology of the endocannabinoid nervous
      system to novel opportunities for therapeutic intervention. This new knowledge
      may facilitate the development of cannabinoid receptor-targeted therapeutics with
      improved safety and efficacy profiles.

PMID- 11448726
TI  - Endothelins: vasoactive modulators of renal function in health and disease.
AB  - Vasoactive autocoids with directly opposing actions on the renal vasculature,
      glomerular function, and in salt and water homeostasis have been demonstrated in
      the kidney. In the renal cortex, endothelin (ET)-1 and angiotensin-II cause
      vasoconstriction, decreasing renal blood flow, and glomerular filtration rate,
      whereas bradykinin and atrial natriuretic peptide cause vasodilation and increase
      glomerular capillary permeability. ET-1 causes vasoconstriction of the afferent
      and efferent arteries and outer medullary descending vasa recta, thereby
      decreasing vasa recta and papillary blood flow, while bradykinin has the opposite
      effect. ET-1 stimulates cell proliferation, increasing the expression of several
      genes, including collagenase, prostaglandin endoperoxidase synthase, and platelet
      derived growth factor. ET-1 promotes natriuresis via the ET-B receptor, causing
      down-regulation of the epithelial Na(+) channel in the renal tubule. Thus, ETs
      affect three major aspects of renal physiology: vascular and mesangial tone,
      Na(+) and water excretion, and cell proliferation and matrix formation.

PMID- 11448727
TI  - Antisense oligonucleotides in cutaneous therapy.
AB  - Antisense oligonucleotides have been the subject of intense interest as research
      tools to elucidate the functions of gene products and as therapeutic agents.
      Initially, their mode of action was poorly understood and the biological effects
      of oligonucleotides were often misinterpreted. However, research into these gene
      based inhibitors of cellular action recently has succeeded in realising their
      exciting potential, particularly as novel therapeutic agents. An emerging
      application of this technology is in cutaneous therapy. The demand for more
      effective dermatological drugs will ensure further development of antisense
      strategies in skin, with key issues being drug delivery, therapeutic target
      selection, and clinical applicability.

PMID- 11448728
TI  - Metabolic complications associated with antiretroviral therapy.
AB  - Mortality rates in the HIV-infected patient population have decreased with the
      advent of highly active antiretroviral therapy (HAART) for the treatment of AIDS.
      Due to the chronic nature of HAART, long-term metabolic complications are
      associated with therapy, such as hyperlipidemia, fat redistribution and diabetes
      mellitus. Currently, all of these symptoms are classified as the lipodystrophy
      (LD) syndrome(s). However, hyperlipidemia and fat redistribution occur
      independently, indicating there may be multiple syndromes associated with HAART.
      Although fat gain/loss and dyslipidemia occur in protease inhibitor (PI) naive
      patients treated with nucleoside reverse transcriptase inhibitors (NRTIs),
      combination therapies (PI and NRTI) accelerate the syndrome. Recent clinical
      trials, cell culture and animal studies indicate that these effects are not drug
      class specific and select PIs, NRTIs and non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) can be associated with metabolic complications. Moreover, the
      effects can vary between various members of the same class of antiretroviral
      agents (i.e. not all PIs cause the same adverse reactions) and may be influenced
      by duration of infection, genetics and environmental factors. Although HAART
      increases the risk of metabolic complications, this does not outweigh the
      benefits of survival. In this review, we summarize the latest clinical and
      scientific information on these metabolic complications, examine current
      hypotheses explaining the syndromes and comment on the existing methods available
      to manage these metabolic side effects.

PMID- 11448729
TI  - Influence of virus strain, challenge dose, and time of therapy initiation on the
      in vivo influenza inhibitory effects of RWJ-270201.
AB  - The influenza virus neuraminidase inhibitor RWJ-270201 (cyclopentane carboxylic
      acid, 3-[cis-1-(acetylamino)-2-ethylbutyl]-4[(aminoiminomethyl)amino]-2-hydroxy
      [cis, 2S, 3R, 4R]) was significantly inhibitory to an infection in mice induced
      by influenza A/NWS/33 (H1N1) virus when oral gavage (p.o.) treatment with 10
      mg/kg per day was delayed at least 60 h after virus exposure. Treatment was 5
      mg/kg twice daily for 5 days. Viral challenge doses of influenza
      A/Shangdong/09/93 (H3N2) virus ranging from the LD(70) to the LD(100) did not
      affect the marked antiviral efficacy of 12.5 mg/kg of RWJ-270201 administered
      p.o. twice daily for 5 days beginning 4 h pre-virus exposure; infection by an
      approximate 2 LD(100) dose (10(8) cell culture infectious doses/ml) was only
      weakly inhibited by the same treatment as seen by significant increase in mean
      day to death. Murine infections induced by influenza A/Bayern/57/93 (H1N1) and
      B/Lee/40 viruses were significantly inhibited by 100, 10, and 1 mg/kg per day of
      RWJ-270201 using the above treatment regimen; influenza A/PR/8/34 (H1N1) virus
      infections in mice were only moderately inhibited, the antiviral effects using
      this virus being lessening of arterial oxygen decline, reduced lung
      consolidation, and inhibition of lung virus titers primarily at the higher
      dosages.

PMID- 11448730
TI  - Mismatched double-stranded RNA (polyI-polyC(12)U) is synergistic with multiple
      anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in
      vitro.
AB  - Although highly active anti-retroviral therapy (HAART) is successful in the
      treatment of HIV infection, problems with toxicity, drug-resistant variants, and
      therapeutic failures have compromised the long-term utility of existing
      combination regimens. Mismatched double-stranded RNA (polyI-polyC(12)U) is an
      immune modulator with inherent anti-HIV activity. Cell toxicities and anti-HIV
      activities of fourteen anti-HIV agents were determined alone and in combination
      with polyI-polyC(12)U. Combination analyses for anti-HIV activity were performed
      at three drug ratios. Using Mixed Dose Effect analyses and the CalcuSyn for
      Windows software package, combination indeces were determined for all drug
      combinations. In general, polyI-polyC(12)U was synergistic in combination with
      abacavir, zidovudine, zalcitabine, didanosine, stavudine, efavirenz, indinavir,
      ritonavir, nelfinavir, and amprenavir. It was synergistic to antagonistic with
      lamivudine, delavirdine, nevirapine, and saquinavir. Thus, polyI-polyC(12)U is
      synergistic with most anti-HIV agents at most drug ratios and across most
      effective concentrations in vitro, although, certain members of each class were
      exceptions. PolyI-polyC(12)U alone was equally active against wild-type HIV and
      HIV resistant to nevirapine, protease inhibitors, or nucleoside analogue reverse
      transcriptase inhibitors. These results suggest that polyI-polyC(12)U should be
      re-evaluated as a potential adjunct therapy in patients who have failed current
      anti-retroviral therapeutic regimens.

PMID- 11448731
TI  - Interactions of human lacrimal and salivary cystatins with adenovirus
      endopeptidase.
AB  - Over 100 serotypes of adenoviruses have been implicated in a variety of human and
      domesticated animal pathologies and some serotypes are widely used as gene
      transfer vectors. Aside from the limited use of vaccines for specific serotypes,
      little effort has been expended in the development of antivirals. The objective
      here was to study the effect of cystatins from human saliva (CS) and tears (CT),
      two points of viral entry, on adenain, the adenovirus type 2 encoded proteinase,
      which is absolutely required for infectivity. Two molecular weight species (13
      and 14.5 kDa) were purified from both fluids at a yield of 5 mg/l. In vitro
      adenain activity was inhibited to 50% at a molar ratio of 5 CS:1 adenain and 3
      CT:1 adenain. By comparison, papain was inhibited to 50% at a molar ratio of 2
      CS:1 papain and 1.5 CT:1 papain. Adenain differed from papain in response to CS
      and chicken egg white (CEW) cystatin in being stimulated at low concentrations,
      and in being inhibited only at very high concentrations of cystatins. The
      presence of cleavage consensus sites specific to adenain in the human cystatins
      could drive the adenain-cystatin interaction predominantly in the substrate
      pathway direction. However, we found that the cystatins could only be digested
      after denaturation and by highly active fresh enzyme preparations. Our
      experiments designed to test the nature of the interaction between adenain and
      cystatins suggest a docking model for the adenain-human cystatin interaction,
      similar to that proposed for papain and CEW. At equilibrium the dissociation
      constant, K(d), between adenain and CT was 1.2 nM. The kinetic parameters
      determined here suggest a simple reversible mechanism for the inhibition of
      adenain by human cystatins. We conclude that the cystatins present in tears and
      saliva are unlikely to play a significant role in inhibiting adenovirus
      infections.

PMID- 11448732
TI  - Isolation and analysis of expression mechanisms of a rice gene, EL5, which shows
      structural similarity to ATL family from Arabidopsis, in response to N
      acetylchitooligosaccharide elicitor.
AB  - Two rice cDNAs, EL5 and RRF1, were isolated and characterized. EL5 was responsive
      to N-acetylchitooligosaccharide, a biotic elicitor active in suspension-cultured
      rice cells. The structural specificity of the elicitor required for the
      expression of EL5 was consistent with other defense reactions observed in the
      experimental system, indicating that the elicitor signal to EL5 is transmitted
      through a single class of receptor-mediated recognition events. However, the
      intracellular signaling pathway to EL5 was distinct from those to other elicitor
      responsive genes. Sequence analysis and alignment showed that a genomic sequence
      stored in rice genome databases in addition to EL5 and RRF1 belongs to the ATL
      family of RING-H2 finger motif proteins first isolated from Arabidopsis.

PMID- 11448733
TI  - Cytosine methylation of plastid genome in higher plants. Fact or artefact?
AB  - DNA methylation of chloroplast genome has been studied in a large variety of
      angiosperm species using restriction enzyme analysis of three genomic loci
      (totally encompassing about 10% of chloroplast genome) and bisulfite genomic
      sequencing of tobacco ribulose bisphosphate carboxylase/oxygenase (large subunit)
      gene (rbcL). Except for CCWGG (W=A or T) sites that were partially refractory to
      the cleavage with methylation sensitive EcoRII in all loci, no cytosine
      methylation was found at the CCGG (MspI/HpaII) and several other restriction
      sites tested. However, EcoRII was unable to completely digest an unmethylated
      CCWGG site in the cloned rbcL gene on plasmid. Further a bisulfite genomic
      sequencing performed on EcoRII-restricted DNA failed to show any 5-methylcytosine
      either within or outside inspected EcoRII sites along the 3' end of rbcL coding
      region. In conclusion our results do not support evidence for methylated cytosine
      residues in plant chloroplast genomes and we suggest that results obtained with
      EcoRII should be interpreted with great care especially when small differences in
      methylation levels are analysed.

PMID- 11448734
TI  - The isolation and characterization of a waxy mutant of diploid wheat (Triticum
      monococcum L.).
AB  - A waxy mutant of diploid wheat (Triticum monococcum L.) was isolated by screening
      M(3) seeds derived from 1% ethyl methanesulfonate (EMS) mutagenized materials
      with KI-I(2) staining of endosperm starch. This mutant was controlled by a single
      waxy gene that completely lacked amylose, the 59-kDa waxy protein and the granule
      bound starch synthase I (GBSS I) activity in the endosperm. Moreover, the T.
      monococcum exhibited the gene dosage effects in terms of amylose content, the
      amount of waxy protein and the GBSS activity. The chain length distribution of
      amylopectin of the waxy mutant endosperm starch slightly differed from that of
      the wild type; the long chains of DP>==19 were more enriched in the waxy
      amylopectin than those in the wild type. The mutant can be an important material
      for studies on starch metabolism and breeding in Triticum species.

PMID- 11448735
TI  - Purification and characterization of dihydroxyacetone phosphate reductase from
      immature seeds of Brassica campestris L.
AB  - Dihydroxyacetone phosphate reductase (DHAP reductase) was purified to apparent
      electrophoretic homogeneity with about 24% recovery from immature seeds of
      Brassica campestris using (NH(4))(2)SO(4) fractionation, affinity chromatography,
      gel filtration and adsorption chromatography. The purified enzyme with molecular
      mass of about 62 kDa was a dimer with subunit molecular mass of 32 kDa. The
      enzyme exhibited maximum activity at pH 7.5 and was highly specific for NADH and
      DHAP. Typical Michaelis-Menten kinetics was obtained for both the substrates with
      K(m) values of 3.3 and 26.6 &mgr;M for NADH and DHAP, respectively. The enzyme
      did not require any metal ion for its activity. Rather, the activity was
      inhibited by Na(+), K(+), Mn(2+), Mg(2+,) and Ca(2+). ATP and fructose-1,6-P(2)
      inhibited the enzyme non-competitively with respect to DHAP with K(i) values of
      0.96 and 1.3 mM, respectively. Substrate interaction kinetics and product
      inhibition studies were consistent with compulsory-ordered bi-bi reaction
      mechanism with NADH being the first substrate to bind and NAD being the last
      product to dissociate. Based on the properties discussed here, it appears that
      the enzyme probably functions for the production of glycerol-3-P from DHAP.

PMID- 11448736
TI  - Characterization of a novel Brassica napus kinase, BNK1.
AB  - A novel plant protein kinase, designated Brassica napus kinase 1 (BNK1), was
      isolated from a lambda-pistil cDNA library. The deduced BNK1 protein contains all
      eleven conserved subdomains of a kinase and encodes a functional serine/threonine
      protein kinase. Phylogenetic analysis of several plant protein kinase subfamilies
      showed that BNK1 is most closely related to the NAK subfamily of protein kinases.
      Genomic Southern blot analysis revealed that BNK1 is a single copy gene in the B.
      napus genome and does not appear to be a member of a multigene family. Expression
      studies revealed that the BNK1 transcript was ubiquitously expressed throughout
      the plant, with highest levels in stem and pistil tissues.

PMID- 11448737
TI  - Assessment of polysomaty, embryo formation and regeneration in liquid media for
      various species of diploid annual Medicago.
AB  - To avoid polyploidy in regenerants the source of explant material should be
      monosomatic. Therefore, the leaf and petiole tissue of five diploid Medicago
      species (Medicago ciliaris, Medicago murex, Medicago orbicularis, Medicago
      polymorpha and Medicago truncatula cv. Jemalong, and the ecotype R108-1) was
      assessed for polysomaty by flow cytometry. For the species studied the frequency
      of 2C nuclei was about 90% in leaves compared with that in petioles. Embryos were
      readily formed from tissue of leaves in liquid media containing 1 mg l(-1) or 4
      mg l(-1) dichlorophenoxyacetic acid (2,4-D). For embryo development two
      procedures were tested - prolonged use of induction medium and treatment with
      polyethylene glycol Mw 6000 (PEG). The highly regenerable genotypes M. truncatula
      cv. Jemalong and R108-1 showed efficient conversion of embryos after maturation
      in liquid medium. The regenerated plants were diploid and with normal phenotype.

PMID- 11448738
TI  - Repression of starch degradation under anaerobic conditions by irregularly high
      levels of ATP in Chlamydomonas sp. MGA161.
AB  - It is generally known that in green algal species the acceleration of starch
      degradation upon transition from aerobic to anaerobic conditions is a result of
      the Pasteur effect in glycolysis. However, the acceleration of starch degradation
      did not occur in cells of Chlamydomonas sp. MGA161. In MGA161 cells, the
      anaerobic ATP level, which decreased to about half of the aerobic ATP level in
      cells of Chlamydomonas reinhardtii after fermentation for 2 h, was kept higher
      than its aerobic ATP level. Gramicidin D, a monovalent cation ionophore, markedly
      decreased the anaerobic and aerobic ATP levels due to the increase in ATP demand,
      accompanied by the acceleration of starch degradation in MGA161 cells. Although
      the anaerobic ATP level of C. reinhardtii cells was partially decreased by
      gramicidin D, starch degradation did not accelerate markedly when compared with
      the result in MGA161 cells. Therefore, starch was degraded at nearly the maximum
      rate in C. reinhardtii cells under anaerobic conditions; in contrast, the high
      level of ATP in MGA161 cells repressed starch degradation even under anaerobic
      conditions, resulting in the absence of the Pasteur effect.

PMID- 11448739
TI  - Fusicoccin- and light-induced activation and in vivo phosphorylation of
      phosphoenolpyruvate carboxylase in vicia guard cell protoplasts.
AB  - The in vivo regulation of phosphoenolpyruvate carboxylase (PEPCase; EC 4.1.1.31),
      was studied in purified guard cell protoplasts (GCPs) of Vicia faba L. Incubation
      of GCPs with fusicoccin (FC) led to the rapid activation of PEPCase and reduced
      its sensitivity towards the feedback-inhibitor malate. This was accompanied by an
      increase in the phosphorylation state of the enzyme. Additionally, PEPCase could
      be transiently activated by white light. Activation and phosphorylation of
      PEPCase upon illumination were dependent on the presence of potassium in the
      incubation medium. Treatment of GCPs with inhibitors of H(+)-ATPases, and with
      abscisic acid (ABA) suppressed the activation of PEPCase in a concentration
      dependent manner. Treatment of protoplasts with butyrate also led to PEPCase
      activation, suggesting a role for the cytosolic pH (pH(cyt)) in the signal
      transduction process. The presented data indicate that guard cell PEPCase is
      regulated by reversible phosphorylation of at least one isoform and elucidate
      first components of the signaling pathway.

PMID- 11448740
TI  - Purine metabolism during white spruce somatic embryo development: salvage of
      adenine, adenosine, and inosine.
AB  - Contribution of the adenine, adenosine and inosine salvage to the purine
      nucleotide and nucleic acid biosynthesis during white spruce (Picea glauca)
      somatic embryo maturation was estimated by in situ assays using [8-(14)C]adenine,
      [8-(14)C]adenosine and [8-(14)C]inosine. The salvage of adenine and adenosine was
      high during the initial stages of embryo maturation, characterized by rapid cell
      proliferation, but it declined upon further embryo development. Inosine salvage
      activity was always much lower than that observed for adenine and adenosine.
      Consistent with these results, activities of adenine phosphoribosyltransferase
      (APRT) and adenosine kinase (AK) measured in the embryo extracts in vitro were
      much higher than the activity of inosine kinase (IK) during all stages of embryo
      development. Utilization of adenosine and inosine for nucleotide and nucleic acid
      synthesis was found to be regulated by the enzymes AK and IK, as the pattern of
      their activities was very similar to the activity of adenosine and inosine
      salvage, estimated with exogenously supplied precursors. However, little
      correlation between salvage of adenine and activity of APRT was found throughout
      somatic embryo maturation. As no adenosine nucleosidase activity was found in
      white spruce embryos, adenosine, but not adenine, seems to be the major end
      product of adenylate catabolism and becomes the predominant substrate for purine
      salvage in vivo. Thus, adenosine salvage appeared to have the most important role
      in white spruce embryos. Studies on the metabolic fate of [8-(14)C]adenine and [8
      (14)C]adenosine suggest that turnover of adenine nucleotides is rapid, as some of
      them are utilized for nucleic acid synthesis. In contrast, most of [8
      (14)C]inosine taken up by the embryos seems to be directly catabolized by the
      conventional purine catabolic pathway via ureides in all stages of embryo
      maturation.

PMID- 11448741
TI  - An N-acetylglucosamine oligomer binding agglutinin (lectin) from ripe Cyphomandra
      betacea Sendt. fruits.
AB  - A new agglutinin (lectin), called CBL3, was purified from the juice of ripe
      Cyphomandra betacea Sendt. fruits until electrophoretically pure to homogeneity.
      The lectin is a homodimer of M(r)=50800 with subunits of 26200 bound by disulfide
      linkages with a pI of 4.9. The agglutinating capacity of the lectin is only
      inhibited by oligomers of N-acetylglucosamine in the following order of potency:
      tetrasaccharide>trisaccharide>disaccharide. CBL3 is not inhibited by N
      acetylglucosamine, the same as all known lectins of the Solanaceae family. The
      human blood group recognition is non-specific. The lectin is a glycoprotein with
      13.6% (w/w) of carbohydrates. The agglutinating activity is not affected by EDTA
      nor by cations. Mitogenic activity was not detected. Heat and pH stability, amino
      acid composition, N-terminal amino acid sequence and immunological properties
      show substantial differences to the reported lectins isolated from the Solanaceae
      family.

PMID- 11448742
TI  - Water deficit effects on solute contribution to osmotic adjustment as a function
      of leaf ageing in three durum wheat (Triticum durum Desf.) cultivars performing
      differently in arid conditions.
AB  - A greenhouse study was carried out using three durum wheat (Triticum durum Desf.)
      cultivars differing in their field performances under arid conditions (Kabir 1,
      poor yield stability; Omrabi 5, high yield stability and Haurani, landrace well
      adapted to drought). Water stress was imposed by withholding water at the
      seedling stage. Water potential (Psi(w)), relative water content (RWC), stomatal
      resistance (SR), and changes in solute concentrations were quantified: (1) as a
      function of leaf development during the stress period; and (2) in young expanded
      and growing leaves harvested at the end of the stress treatment. Psi(w), RWC and
      SR were almost unaffected by leaf age in controls. In contrast, solute
      concentrations appeared to vary in the course of leaf development. During the
      stress treatment, Psi(w) and RWC decreased and SR increased in all cultivars; the
      changes were most often largest in Omrabi 5, lowest in Haurani and intermediate
      in Kabir 1. Water stress also increased sugar and proline concentrations and
      decreased nitrate levels. Young expanded and growing leaves differed in terms of
      Psi(w), RWC and osmotic adjustment (OA). The capacity of OA was greater in
      growing than in expanded leaves, especially in the two cultivars best adapted to
      aridity, and allowed turgor maintenance in these genotypes. Sugars were the main
      solutes that contributed to OA particularly in growing leaves followed by proline
      and then quaternary ammonium compounds. The contributions of these organic
      solutes to OA tended to be higher in Omrabi 5 and in Haurani than in Kabir 1.
      Inorganic solutes, however, did not seem to play an important role in OA despite
      their high proportion in total solutes.

PMID- 11448743
TI  - Comparative salt tolerance of amphidiploid and diploid Brassica species.
AB  - Salt (NaCl) tolerance of three amphidiploid Brassica species, B. napus (AC
      genome), B. carinata (BC genome), and B. juncea (AB genome), and their putative
      diploid relatives, B. campestris (A genome), B. oleracea (C genome) and B. nigra
      (B genome) was examined under glasshouse conditions. The plants were grown in
      sand culture throughout the study period (51 days). Twenty-three day old plants
      of all six species were subjected for 28 days to control (0 mol m(-3) NaCl), 100
      and 200 mol m(-3) NaCl in Hoagland nutrient solution. Under saline conditions,
      growth of the three amphidiploid species was significantly greater in shoot and
      root weights, and seed yield was greater than that of the diploids. The
      amphidiploids accumulated lower Na(+) but higher K(+) in their shoots and roots,
      the K/Na ratio therefore being considerably higher than those of the diploids.
      Ca(2+) accumulation was similar in the diploids and amphidiploids, and the Cl(-)
      accumulation pattern was not consistent in the different species. The occurrence
      of high salt tolerance of amphidiploids, and their enhanced K/Na discrimination
      with respect to their diploid relatives, suggests that salt tolerance has been
      obtained from A and C genomes and the latter trait from all three genomes (A, B,
      and C).

PMID- 11448744
TI  - Effects of ipt gene expression on the physiological and chemical characteristics
      of Artemisia annua L.
AB  - An isopentenyl transferase gene (ipt) from T-DNA was transferred into Artemisia
      annua L. via Agrobacterium tumefaciens. The ipt gene was placed in a binary
      vector under the control of the CaMV 35S promoter. Leaf explants were infected
      with A. tumefaciens LBA4404 containing pBIipt to induce the buds. Nineteen shoot
      lines were selected, which were resistant to kanamycin. Polymerase chain
      reactions and Southern blotting confirmed that at least five shoot lines
      contained the foreign gene. The results of RT-PCR and Northern blotting analyses
      suggested that the foreign ipt gene of the transgenic shoot was expressed.
      Cytokinins, chlorophyll and artemisinin contents were found increased at
      different degree. Content of cytokinins (iPA and iP) was elevated 2- to 3-fold,
      chlorophyll increased 20-60% and artemisinin increased 30-70% compared with the
      control plants, respectively. A direct correlation was found between the contents
      of cytokinins, chlorophyll and artemisinin. This may be the first report on the
      relationship between endogenous cytokinin content and the production of secondary
      metabolites in plants.

PMID- 11448745
TI  - Coat protein RNAs-mediated protection against Andean potato mottle virus in
      transgenic tobacco.
AB  - The expression of translatable sequences of either one of the two Andean potato
      mottle virus (APMoV) coat protein (CP) genes (CP22 and CP42) and of the
      nontranslatable sequence of CP42 in transgenic tobacco provided protection
      against APMoV. Resistance was mediated by CP transgene RNAs rather than the
      protein, as an inverse correlation between resistance and the accumulation levels
      of CPs transgene mRNAs was observed. These data indicated that a post
      transcriptional gene silencing (PTGS) mechanism is likely involved in the APMoV
      CP RNA-mediated protection. Moreover, the HindIII-AccI restriction pattern of the
      CP22 transgene was different in susceptible and resistant transgenic plants,
      suggesting the involvement of methylation in PTGS. Southern blot experiments also
      revealed that CPs transgene insertion loci and organisation in the plant genome
      may play a role in determining the degree of protection.

PMID- 11448746
TI  - Isolation of a flax pectin methylesterase promoter and its expression in
      transgenic tobacco.
AB  - Pectin methylesterases (PME) catalyze the de-esterification of methoxylated
      pectins in plant cell walls. We have isolated a 1.9 kb regulatory region upstream
      from the Lupme3 coding sequence of Linum usitatissimum L. (flax) using a
      'Polymerase Chain Reaction (PCR) walking' strategy. Two 5' truncated deletion
      fragments (1.5 and 0.44 kb) of this potential promoter sequence were inserted
      upstream of the gus reporter gene in order to study their expression in
      transgenic plants. These constructs were transferred into Nicotiana tabacum, a
      heterologous system using Agrobacterium tumefaciens. Expression of the reporter
      gene was analyzed in regenerated transgenic plants and calli to study the
      promoter activities of these sequences. This expression was observed in calli
      with both constructs. In contrast, expression in organs was only detected in
      tobacco plants transformed with the largest (1.5 kb) construct. This long
      fragment triggered expression in roots and immature or vitrified leaves.
      Expression in both organs was localized in the vasculature, but also detected in
      the root meristem. These results are the first evidence, to our knowledge, of the
      spatial and temporal regulation of a specific pme promoter of flax. Localization
      of Lupme3 promoter activity in vascular tissues of immature organs provides an
      insight into the role of this PME isoform in cell elongation and differentiation.

PMID- 11448747
TI  - Ascorbate, glutathione and related enzymes in chloroplasts of tomato leaves
      infected by Botrytis cinerea.
AB  - The effect of Botrytis cinerea infection on the total pool sizes of ascorbate,
      glutathione and their redox status, the activities of ascorbate-glutathione cycle
      related enzymes, APX, DHAR, GR as well as GST and GSH-Px activities in
      chloroplasts isolated from tomato leaves were studied. An accelerated chlorophyll
      loss in chloroplasts from infected leaves was observed. The AA content was not
      changed considerably but a burst in DHA formation, up to 319% of control, and a
      significant prooxidative shift in the ascorbate redox status were found in
      chloroplasts from infected leaves. A massive progressive decrease in GSH and
      total glutathione contents as well as GR activity increase were found after
      infection. However, similar but less-pronounced glutathione-related changes were
      observed in control suggesting that they could be at least partly the result of
      B. cinerea induced promotion of senescence and not a specific response to
      pathogen infection. As shown by the analysis of ascorbate-glutathione cycle
      related enzyme activities as well as correlations between the two antioxidants
      and enzymes responsible for keeping them in the reduced state GSH is the limiting
      factor for the whole cycle operation in chloroplasts. This is in accordance with
      our previous results for the whole-cell extracts.

PMID- 11448748
TI  - Characterization of sucrose uptake system in cassava (Manihot esculenta Crantz).
AB  - A leaf disc system was developed to study sucrose uptake in cassava (Manihot
      esculenta Crantz). The uptake of (U-(14)C) sucrose by cassava leaf discs followed
      Michaelis-Menten kinetics with a K(m) value for sucrose of 1.3 mM. It was found
      to be strongly inhibited by sulfhydryl reagents, N-ethylmaleimide, p
      chloromercuribenzene sulfonate and iodoacetate. Several metabolic inhibitors were
      also tested. Among these, dinitrophenol, chlorocarbonyl cyanide phenylhydrazone,
      phloridzin and vanadate inhibited the sucrose uptake by the leaf discs.
      Linamarin, the main cassava cyanogenic glucoside, strongly inhibited the sucrose
      uptake by the leaf discs, while other cyanogenic glycosides tested (prunasin and
      amygdalin) showed a much weaker inhibition. A linamarin analog,
      isopropylthioglucoside, was a weaker inhibitor than p-nitrophenyl glucosides
      (both alpha and beta forms). Cassava root discs were also capable of taking up
      sucrose, but linamarin activated its uptake. The observations suggested that
      linamarin may regulate the sucrose transport in cassava.

PMID- 11448749
TI  - Interaction of a mulberry leaf lectin with a phytopathogenic bacterium, P.
      syringae pv mori.
AB  - Two N-glycolylneuraminic acid-specific lectins, MLL 1 and 2, from leaves of Morus
      alba were studied for their anti-bacterial activity against P. syringae pv mori,
      which was a specific pathogenic bacterium of the mulberry leaf. MLL 1 but not MLL
      2 was found to induce the agglutination of P. syringae pv mori. The MLL 1 can
      induce the agglutination only at the exponential phase of the bacterial growth in
      a liquid medium and the agglutination was specifically inhibited by N
      glycolylneuraminic acid, N-acetylgalactosamine at 12.5 mM and bovine submaxillary
      mucin at 0.05 &mgr;g/ml.

PMID- 11448750
TI  - High frequency of cytogenetic aberration in transgenic oat (Avena sativa L.)
      plants.
AB  - Cytological abnormalities were observed in transgenic oat (Avena sativa L. cv.
      GAF/Park-1) produced by microprojectile bombardment of mature seed-derived highly
      regenerative tissues. Of the plants from 48 independent transgenic lines
      examined, plants from only 20 lines (42%) were karyotypically normal (2n=6x=42)
      without detectable chromosomal aberrations; plants from 28 lines (58%) had
      chromosomal variation, i.e. aneuploids and structural changes. No significant
      difference in cytological aberration was observed between the two different
      culturing systems used for transformation: 57% chromosomal abnormalities in
      plants derived from D'BC2 medium (2.0 mg/l 2,4-D, 0.1 mg/l BAP and 5.0 &mgr;M
      cupric sulfate) used for tissue initiation and maintenance and 60% in plants from
      tissue initiated on D'BC2 and maintained on DBC3 (1.0 mg/l 2,4-D, 0.5 mg/l BAP
      and 5.0 &mgr;M cupric sulfate). Comparative differences in chromosomal status
      frequently occurred among plants regenerated from the same T(0) line. The most
      common cytological aberration in transgenic plants was aneuploidy, followed by
      deletion of chromosomal segments; no change in ploidy level was observed. In
      contrast, nontransgenic plants, regenerated from tissues comparable in age and
      culture media to that used for transgenic tissues, had a much lower percentage of
      karyotypic abnormality (0-14%). Our data indicate that some stress(es) imposed by
      the transformation process, e.g. osmotic treatment, bombardment and selection,
      leads to cytological variation in transgenic oat plants, an observation similar
      to that observed in our recent studies with transgenic barley plants.

PMID- 11448751
TI  - Gene tagging in rice: a high throughput system for functional genomics.
AB  - Rice, with its small genome size and well-characterized molecular information, is
      an ideal model plant for cereal genomics research. Sequence of the rice (Oryza
      sativa) genome will be determined by the International Rice Genome Sequencing
      Project (IRGSP) in the near future. Therefore, a large population of mutant
      plants should be required for adequately assigning function to the abundant
      sequence information. Here we summarize strategies as well as the progress that
      has been made in producing gene tags that may be invaluable for understanding the
      functional genomics of rice.

PMID- 11448752
TI  - The initiation of elongation growth during long-term low-temperature stay of
      spring-type oilseed rape may trigger loss of frost resistance and changes in
      photosynthetic apparatus.
AB  - The aim of the present investigation was to determine if the loss of frost
      resistance observed in spring-type oilseed rape during winter may be the effect
      of the tendency to start elongation growth during the prolonged low-temperature
      stay. Interactions between elongation growth rate, properties of photosynthetic
      apparatus and frost resistance were studied under these conditions in spring and
      winter cultivars of oilseed rape. Both spring and winter cultivars of oilseed
      rape reached the maximal frost resistance after 6 weeks at +5 degrees C.
      Photosynthetic apparatus of both cultivars acclimated to functioning in cold. The
      resistance of winter type plants remained unchanged at the end of the experiment
      (10 weeks) whereas spring-type plants lost the maximal resistance in subsequent
      weeks. It was preceded in the 7th week of low-temperature stay by acceleration of
      elongation growth without an increase in dry matter accumulation. A gradual loss
      of photosynthetic activity was also observed during this period. It was
      manifested as a decrease in antenna trapping efficiency, photochemical and non
      photochemical fluorescence quenching and actual quantum yield of PSII without
      affecting apparent quantum yield of PSII. At the 70th day of the experiment, a
      decrease in CO(2) exchange and dry matter accumulation were even observed. The
      possible relationships between growth rate and functioning of photosynthetic
      apparatus are discussed.

PMID- 11448753
TI  - Modulation of nitrate reductase activity in cucumber (Cucumis sativus) roots.
AB  - Nitrate reductase (NR) (EC 1.6.6.1) activity and NR activation state, i.e.
      activity in the presence of Mg(2+) relative to activity in the absence of Mg(2+),
      in cucumber (Cucumis sativus) leaves increased in the light and decreased in the
      dark. In contrast to leaves, NR activation state in the roots did not show
      light/dark-dependent changes. Root NR was activated by anoxia or by addition of
      uncoupler (CCCP) or mannose. These treatments decreased ATP levels in root
      tissue. On the contrary, high oxygen supply promoted some NR inactivation. When
      an extract from anoxic roots was preincubated with ATP, NR was gradually
      inactivated. Subsequent addition of 5'-AMP resulted in a remarkable reactivation
      of the enzyme. NR extracted from hyperoxygenated roots was activated by
      preincubation with 5'-AMP, and the process was reversed by ATP. These results
      suggest the participation of adenine nucleotides on the in vivo modulation of NR
      activity in cucumber roots. NR was activated in vivo by cellular acidification
      and inactivated by alkalinisation. The acid-induced activation of NR was greatly
      prevented by okadaic acid, a protein phosphatase inhibitor. Our data indicate
      that, as in barley roots, anoxia, uncouplers, and mannose feeding activate
      cucumber root NR, at least partly, by enhancing NR dephosphorylation via a
      decrease in the internal level of ATP and a concomitant cellular acidification.

PMID- 11448754
TI  - Agrobacterium tumefaciens-mediated genetic transformation of mungbean (Vigna
      radiata L. Wilczek) - a recalcitrant grain legume.
AB  - Agrobacterium-mediated transformation of Vigna radiata L. Wilczek has been
      achieved. Hypocotyl and primary leaves excised from 2-day-old in-vitro grown
      seedlings produced transgenic calli on B(5) basal medium supplemented with 5x10(
      6) M BAP, 2.5x10(-6) M each of 2,4-D and NAA and 50 mg l(-1) kanamycin after co
      cultivation with Agrobacterium tumefaciens strains, LBA4404 (pTOK233), EHA105
      (pBin9GusInt) and C58C1 (pIG121Hm) all containing beta-glucuronidase (gusA) and
      neomycin phosphotransferase II (nptII) marker genes. Transformed calli were found
      resistant to kanamycin up to 1000 mg(.)l(-1). Gene expression of kanamycin
      resistance (nptII) and gusA in transformed calli was demonstrated by nptII assay
      and GUS histochemical analysis, respectively. Stable integration of T-DNA into
      the genome of transformed calli of mungbean was confirmed by Southern blot
      analysis. Transgenic calli could not regenerate shoots on B(5) or B(5) containing
      different cytokinins or auxins alone or in combination. However, for the first
      time, transformed green shoots showing strong GUS activity were regenerated
      directly from cotyledonary node explants cultured after co-cultivation with
      LBA4404 (pTOK233) on B(5) medium containing 6-benzylaminopurine (5x10(-7) M) and
      75 mg l(-1) kanamycin. The putative transformed shoots were rooted on B(5)+indole
      3-butyric acid (5x10(-6) M) within 10-14 days and resulted plantlets subsequently
      developed flowers and pods with viable seeds in vitro after 20 days of root
      induction. The stamens, pollen grains and T(0) seeds showed GUS activity.
      Molecular analysis of putative transformed plants revealed the integration and
      expression of transgenes in T(0) plants and their seeds.

PMID- 11448755
TI  - Pharmacological evidence for the implication of both cyclic GMP-dependent and 
      independent transduction pathways within auxin-induced stomatal opening in
      Commelina communis (L.).
AB  - It has been previously suggested that auxin-induced stomatal opening results from
      at least two transduction pathways, one of which involves cyclic GMP (cGMP) as
      the mediator within a Ca(2+) signalling cascade. This hypothesis was investigated
      further in epidermal peels of Commelina communis by comparing the effects of
      potential inhibitors of plant Ca(2+)-dependent enzymes on the stomatal opening
      responses to the auxin indolyl-3-butyric acid (IBA) and to the cGMP membrane
      permeable derivative 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP). In
      the 30-50 &mgr;M range, the potential plant calmodulin (CaM) antagonist N
      (aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) positively interacted with
      IBA but not with 8-Br-cGMP to open the stomata. The CaM antagonists W-7 (in the
      10-20 &mgr;M range) and N-(aminohexyl)-1-naphthalenesulphonamide (40 &mgr;M), the
      potential inhibitors of plant protein kinases 1-(5-isoquinolinylsulfonyl)-2
      methylpiperazine (20 and 200 &mgr;M) and K-252a (0.6 &mgr;M), and cyclosporine A
      and FK506, potential inhibitors of plant homologs of Ca(2+)-CaM complex
      (Ca(2+)/CaM)-dependent protein phosphatase 2B, prevented the IBA and 8-Br-cGMP
      responses by about 70% and 100%, respectively. Together, these results provide
      indirect pharmacological evidence that, in addition to the cGMP-dependent
      pathway, the auxin signal is transduced through at least one cGMP-independent
      pathway.

PMID- 11448756
TI  - Transfer of salt tolerance from Aeleuropus littorulis sinensis to wheat (Triticum
      aestivum L.) via asymmetric somatic hybridization.
AB  - Protoplasts of wheat c.v. Jinan 177 were fused by PEG method with the UV
      irradiated protoplasts of A. littoralis - a salt tolerant plant intertribal to
      wheat. The early-formed regenerated clones were identified as hybrids by
      chromosome, isozyme and RAPD analysis. Their salt-tolerant ability was compared
      with both parents in relative growth, proline accumulation and Na(+)/K(+) ratio
      under salt stress, and was proved higher than wheat, indicating some
      corresponding genes coding salt-tolerance had been transferred into the hybrids.
      However, the hybrid clones could only differentiated to albino plants. Further
      investigations are now being conducted to solve this problem.

PMID- 11448757
TI  - Genotypic control of high-frequency adventitious shoot regeneration via somatic
      organogenesis in loblolly pine.
AB  - Mature zygotic embryos of 24 genotypes of loblolly pine (Pinus taeda L.) were
      used as explants to establish an adventitious shoot regeneration system through
      somatic organogenesis. Callus formation frequencies of 18.2 (genotype 11-1103) 
      77.7% (genotype 7-100) have been induced from mature zygotic embryos of all
      genotypes tested on callus induction medium (basal salts) containing 2,4
      dichlorophenoxyacetic acid (2,4-D) or alpha-naphthaleneacetic acid (NAA), 6
      benzyladenine (BA), and kinetin. Adventitious shoot regeneration via
      organogenesis with the frequency of 5.4 (genotype 11-1103 and 7-2) -77.2%
      (genotype 8-1082) was obtained from callus and tissue cultures derived from
      mature zygotic embryos of 24 genotypes of loblolly pine. The highest mean number
      of 18 adventitious buds per piece of callus 0.5x0.5 cm(2) in size was obtained
      from genotype 8-1082. Elongation of adventitious buds was achieved on TE medium
      supplemented with 0.5 mg/l indole-3-butyric acid (IBA) and 1 mg/l BA. After
      rooting, regenerated plantlets were established in soil. These results suggested
      that adventitious shoot regeneration via somatic organogenesis was influenced by
      the genotypes. The in vitro regeneration procedure established in this
      investigation could be used for clonal micropropagation of some genotypes of
      loblolly pine, as well as for establishing a transformation system in coniferous
      species.

PMID- 11448758
TI  - Involvement of GTP-binding protein in the induction of phytoalexin biosynthesis
      in cultured carrot cells.
AB  - Biosynthetic activity of carrot phytoalexin 6-methoxymellen was induced in cell
      suspension culture by the treatment with oligogalacturonide elicitor; however,
      the elicitor-induced activity appreciably reduced in the presence of suramin, a
      potent inhibitor of GTP-binding proteins. In contrast, addition of G-protein
      activators, such as mastoparan or GTP-gamma-S, to carrot cell culture triggered 6
      methoxymellein production even in the absence of uronide elicitor. An appreciable
      GTPase activity was found in purified plasma membrane of cultured carrot cells,
      and the hydrolytic activity was significantly increased by the addition of
      elicitor. Carrot plasma membrane was capable of associating with GTP-gamma-S, and
      the binding ability was markedly increased in the presence of elicitor. However,
      the binding activity markedly decreased when the membrane preparation was pre
      incubated with GTP but not with ATP. These observations strongly suggest that a
      certain GTP-binding protein located at plasma membrane of cultured carrot cells
      plays an important role in the oligogalacturonide elicitor-induced 6
      methoxymellein production.

PMID- 11448759
TI  - Synthesis of hemoglobins in rice (Oryza sativa var. Jackson) plants growing in
      normal and stress conditions.
AB  - In rice (Oryza sativa var. Jackson) at least three copies of hemoglobin (hb) gene
      exist. Rice hb1 and hb2 genes are differentially expressed in roots and leaves
      from mature plants. We used polyclonal antibodies raised to recombinant rice Hb1
      and Western blotting to analyze the synthesis of Hbs in rice plants growing under
      normal or stress conditions. Results showed that rice Hbs are synthesized in
      coleoptiles, seminal roots and embryos from seeds germinated for 6 days, and also
      in leaves and roots from plants 2-14 weeks after germination. Analysis of Hb
      synthesis in stressed rice showed that: (i) level of Hbs was higher in etiolated
      than control plants, (ii) level of Hbs increased in roots from flooded rice, and
      (iii) level of Hbs did not change under oxidative (H(2)O(2)), nitrosative (SNP)
      and hormonal (2,4-D) stresses. These results suggest that the effect of light
      withdrawal in etiolated leaves and O(2)-limiting conditions in flooded roots, but
      not oxidative, nitrosative and hormonal stresses, modulate the synthesis of rice
      Hbs.

PMID- 11448760
TI  - Genes induced during early response to Meloidogyne incognita in roots of
      resistant and susceptible alfalfa cultivars.
AB  - A cDNA library made to RNA from roots of Meloidogyne incognita (root-knot
      nematode) susceptible alfalfa cv. Lahontan seedlings 72 h after root-knot
      nematode inoculation was differentially screened with cDNA made from uninoculated
      control and M. incognita infested (72 h) root RNA. Of the six cDNAs isolated, the
      deduced amino acid sequences of four showed significant homology to sequences
      present in the databank, while two were pioneer sequences. The four cDNAs with
      matches to known sequences include those for glycine-rich protein, the
      gluconeogenic pathway enzyme phosphoenolpyruvate carboxykinase, an isoflavone
      reductase-like protein, and metallothionein. We have followed the expression of
      these genes during the course of nematode infection in both the susceptible and
      resistant host and also in different plant organs. Based on these analyses, the
      genes induced early in nematode infection are related either to metabolic
      pathways or to stress/defense.

PMID- 11448761
TI  - Loss of stress-induced expression of catalase3 during leaf senescence in
      Arabidopsis thaliana is restricted to oxidative stress.
AB  - Different stress conditions can induce changes in the activity of the antioxidant
      enzymes superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC
      1.11.1.11) and catalase (CAT, EC 1.11.1.6). The enzyme activities of all SOD and
      APX isoforms detected in young Arabidopsis leaves remained unaffected or slightly
      decreased after moderate paraquat treatment. While CAT2 activity also remained
      unaffected under these conditions, CAT3 enzyme activity was enhanced. In contrast
      to the enzyme activities, mRNA levels of both cat2 and cat3 were enhanced under
      oxidative stress induced by either paraquat or the fungal toxin cercosporin. This
      indicates that, with respect to enzyme activity level, CAT3 is the enzyme which
      is most sensitive to oxidative stress in this developmental stage and that the
      enzyme activity of CAT2 is possibly regulated at the post-transcriptional level.
      Interestingly, cat3 mRNA level and CAT3 activity are not elevated by paraquat
      treatment in senescing leaves. In contrast, the response to other stress
      conditions, such as water stress induced by flooding of detached leaves and heat
      stress, is maintained in senescing leaves. Since changes in stress response are
      not a general phenomenon in leaf senescence but appear to be restricted to
      oxidative stress, this might be a specific mechanism to promote senescence in
      Arabidopsis thaliana.

PMID- 11448762
TI  - Regulation of anthocyanin biosynthesis in UV-A-irradiated cell cultures of carrot
      and in organs of intact carrot plants.
AB  - Two cell lines of Daucus carota are known to differ with respect to anthocyanin
      accumulation. cDNA clones encoding enzymes involved in anthocyanidin
      biosynthesis, namely phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), chalcone
      synthase (CHS; EC 2.3.1.74), flavanone 3-hydroxylase (F3H; EC 1.14.11.9),
      dihydroflavonol 4-reductase (DFR; EC 1.1.1.219) and leucoanthocyanidin
      dioxygenase (LDOX; EC 1.14.11.-), were isolated from libraries derived from cell
      cultures. Northern blot analysis of anthocyanin-accumulating (DCb) and non
      accumulating (DCs) cell cultures of carrot showed that the anthocyanin pathway in
      these anthocyanin-free DCs cells is blocked. The expression of CHS1, DFR1 and
      LDOX is not detectable. However, F3H and DFR2 behave differently. In the European
      wild carrot (Daucus carota ssp. carota) the structural genes coding for the
      enzymes responsible for anthocyanin biosynthesis are strongly expressed in organs
      which accumulate anthocyanins. Only the dark-purple coloured petals of the
      central flowers of the inflorescence and to a certain extent the white flowers
      and the leaves but not the stems and the roots transcribe these genes. To study
      the effect of anthocyanins as UV-screens the expression of a protein
      indispensable for cell proliferation like alpha-tubulin (TUB) was monitored.

PMID- 11448763
TI  - Processing and localization of bovine beta-casein expressed in transgenic soybean
      seeds under control of a soybean lectin expression cassette.
AB  - We have examined the processing and subcellular localization of a chimeric gene
      consisting of the bovine milk protein, beta-casein, under the control of a
      soybean seed lectin promoter and its 32 amino acid signal sequence in the seeds
      of transgenic soybean plants. The beta-casein expressed in developing soybean
      seeds is a doublet with apparent molecular weight slightly smaller than the
      bovine beta-casein and expression of the protein was highest in immature
      cotyledons. The casein proteins were purified from the immature soybean seeds by
      immunoaffinity chromatography and were analyzed by two-dimensional gel
      electrophoresis, blotting, and amino terminal sequencing. The N-terminal
      sequences of both of the doublet soybean casein polypeptides were identical to
      the N-terminal sequence of the bovine beta-casein indicating that the 32 amino
      acid lectin signal sequence was cleaved precisely from the chimeric protein in
      developing soybean seeds. Analysis of the purified soybean beta-casein
      polypeptides by mass spectrometry (MALDI-MS) showed that they are not
      phosphorylated. Absence of added phosphate groups is the cause of the size
      difference between the soybean beta-casein and native bovine beta-casein protein.
      Immunolocalization experiments showed that the casein protein was found in the
      protein storage vacuoles (PSV) in developing and mature soybean seeds. The
      precise removal of the 32 amino acid lectin amino terminal sequence from the
      chimeric lectin-casein fusion suggests that the lectin expression cassette can be
      used for production of pharmaceutical or other recombinant proteins of added
      value in the developing soybean seed.

PMID- 11448764
TI  - Pyk10, a seedling and root specific gene and promoter from Arabidopsis thaliana.
AB  - Pyk10 is a root and hypocotyl specific myrosinase from Arabidopsis thaliana.
      Northern analysis revealed the root specific expression of pyk10. In order to
      study the pyk10 promoter and the genomic structure of the gene, a genomic clone
      was isolated and sequenced. The clone contained the complete pyk10 gene and a
      promoter region of 3569 bp. The gene spans 2963 bp and consists of 12 exons and
      11 introns, a structure that reflects the common gene organization of
      myrosinases. Within the promoter sequence, different development specific, organ
      specific, elicitor and plant hormone responsive regulatory elements could be
      identified, which also occur in other promoters. To determine the pattern of
      expression, four different 5'-promoter deletion fragments were linked to a ss
      glucuronidase (gus) reporter gene and transformed into A. thaliana. The results
      demonstrated that the pyk10 promoter mediates a developmental gene activity with
      a strong emphasis in the root. Cis-acting sequences regulating root specific
      expression were identified to reside in the two promoter fragments B and C.

PMID- 11448765
TI  - Compatibility of a wild type and its genetically modified Sinorhizobium strain
      with two mycorrhizal fungi on Medicago species as affected by drought stress.
AB  - The effect of double inoculation with two strains of Sinorhizobium meliloti [the
      wild type (WT) strain GR4 and its genetically modified (GM) derivative
      GR4(pCK3)], and two species of arbuscular mycorrhizal (AM) fungi (Glomus
      deserticola and Glomus intraradices) was examined in a microcosm system on three
      species of Medicago (M. nolana, M. rigidula, M. rotata). Two water regimes (80
      and 100% water holding capacity, WHC) were assayed. The efficiency of each AM
      fungus increasing plant growth, nutrient content, nodulation and water-stress
      tolerance was related to the Sinorhizobium strains and Medicago species. This
      indicates selective and specific compatibilities between microsymbionts and the
      common host plant. Differential effects of the mycorrhizal isolates were not
      associated with their colonizing ability. Nodulation and mycorrhizal dependency
      (MD) changed in each plant genotype in accordance with the Sinorhizobium strain
      and AM fungi involved. Generally, Medicago sp. MD decreased under water-stress
      conditions even when these conditions did not affect AM colonization (%). Proline
      accumulation in non-mycorrhizal plant leaves was increased by water stress,
      except in M. rotata plants. Differences in proline accumulation in AM-colonized
      plants suggest that both the AM fungus and the Sinorhizobium strain were able to
      induce different degrees of osmotic adjustment. Mycorrhizal plants nodulated by
      the WT strain accumulated more proline in M. rigidula and M. rotata under water
      stress than non-mycorrhizal plants. Conversely, mycorrhizal plants nodulated by
      the GM strain accumulated less proline in response to both AM colonization and
      drought. These results indicated changes in the synthesis of this nitrogenous
      osmoregulator product associated with microbial inoculation and drought
      tolerance. Mycorrhizal plants nodulated by the GM Sinorhizobium strain seem to
      suffer less from the detrimental effect of water stress, since under water
      limitation relative plant growth, percentage of AM colonization, root dry weight
      and the highest R/S ratio remained the same. The fact that GM nodulated plants
      are better adapted to drought stress could be of practical interest and the
      management of GM microorganism inoculation may be crucial for biotechnological
      approaches to improving crop yield in dry environments.

PMID- 11448766
TI  - Detection of DNA methylation changes in micropropagated banana plants using
      methylation-sensitive amplification polymorphism (MSAP).
AB  - The extent of DNA methylation polymorphisms was evaluated in micropropagated
      banana (Musa AAA cv. 'Grand Naine') derived from either the vegetative apex of
      the sucker or the floral apex of the male inflorescence using the methylation
      sensitive amplification polymorphism (MSAP) technique. In all, 465 fragments,
      each representing a recognition site cleaved by either or both of the
      isoschizomers were amplified using eight combinations of primers. A total of 107
      sites (23%) were found to be methylated at cytosine in the genome of
      micropropagated banana plants. In plants micropropagated from the male
      inflorescence explant 14 (3%) DNA methylation events were polymorphic, while
      plants micropropagated from the sucker explant produced 8 (1.7%) polymorphisms.
      No DNA methylation polymorphisms were detected in conventionally propagated
      banana plants. These results demonstrated the usefulness of MSAP to detect DNA
      methylation events in micropropagated banana plants and indicate that DNA
      methylation polymorphisms are associated with micropropagation.

PMID- 11448767
TI  - Light-dependent interaction between Drosophila CRY and the clock protein PER
      mediated by the carboxy terminus of CRY.
AB  - BACKGROUND: The biological clock synchronizes the organism with the environment,
      responding to changes in light and temperature. Drosophila CRYPTOCHROME (CRY), a
      putative circadian photoreceptor, has previously been reported to interact with
      the clock protein TIMELESS (TIM) in a light-dependent manner. Although TIM
      dimerizes with PERIOD (PER), no association between CRY and PER has previously
      been revealed, and aspects of the light dependence of the TIM/CRY interaction are
      still unclear. RESULTS: Behavioral analysis of double mutants of per and cry
      suggested a genetic interaction between the two loci. To investigate whether this
      was reflected in a physical interaction, we employed a yeast-two-hybrid system
      that revealed a dimerization between PER and CRY. This was further supported by a
      coimmunoprecipitation assay in tissue culture cells. We also show that the light
      dependent nuclear interactions of PER and TIM with CRY require the C terminus of
      CRY and may involve a trans-acting repressor. CONCLUSIONS: This study shows that,
      as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C
      terminus of CRY is involved in mediating light responses. A model for the light
      dependence of CRY is discussed.

PMID- 11448768
TI  - Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell
      migration.
AB  - BACKGROUND: Cranial neural-crest (CNC) cells originate from the lateral edge of
      the anterior neuroepithelium and migrate to form parts of the peripheral nervous
      system, muscles, cartilage, and bones of the face. Neural crest-cell migration
      involves the loss of adhesion from the surrounding neuroepithelium and a
      corresponding increase in cell adhesion to the extracellular matrix (ECM) present
      in migratory pathways. While proteolytic activity is likely to contribute to the
      regulation of neural crest-cell adhesion and migration, the role of a neural
      crest-specific protease in these processes has yet to be demonstrated. We
      previously showed that CNC cells express ADAM 13, a cell surface
      metalloprotease/disintegrin. Proteins of this family are known to act in cell
      cell adhesion and as sheddases. ADAMs have also been proposed to degrade the ECM,
      but this has not yet been shown in a physiological context. RESULTS: Using a
      tissue transplantation technique, we show that Xenopus CNC cells overexpressing
      wild-type ADAM 13 migrate along the same hyoid, branchial, and mandibular
      pathways used by normal CNC cells. In contrast, CNC cell grafts that express
      protease-defective ADAM 13 fail to migrate along the hyoid and branchial
      pathways. In addition, ectopic expression of wild-type ADAM 13 results in a gain
      of-function phenotype in embryos, namely the abnormal positioning of trunk neural
      crest cells. We further show that explanted embryonic tissues expressing wild
      type, but not protease-defective, ADAM 13 display decreased cell-matrix adhesion.
      Purified ADAM 13 can cleave fibronectin, and tissue culture cells that express
      wild-type, but not protease-defective, ADAM 13 can remodel a fibronectin
      substrate. CONCLUSIONS: Our findings support the hypothesis that the protease
      activity of ADAM 13 plays a critical role in neural crest-cell migration along
      defined pathways. We propose that the ADAM 13-dependent modification of ECM
      and/or other guidance molecules is a key step in the directed migration of the
      CNC.

PMID- 11448769
TI  - Fission yeast Clp1p phosphatase regulates G2/M transition and coordination of
      cytokinesis with cell cycle progression.
AB  - BACKGROUND: In Saccharomyces cerevisiae the mitotic-exit network (MEN) functions
      in anaphase to promote the release of the Cdc14p phosphatase from the nucleolus.
      This release causes mitotic exit via inactivation of the cyclin-dependent kinase
      (Cdk). Cdc14p-like proteins are highly conserved; however, it is unclear if these
      proteins regulate mitotic exit as in S. cerevisiae. In Schizosaccharomyces pombe
      a signaling pathway homologous to the MEN and termed the septation initiation
      network (SIN) is required not for mitotic exit, but for initiation of cytokinesis
      and for a cytokinesis checkpoint that inhibits further cell cycle progression
      until cytokinesis is complete. RESULTS: We have identified the S. pombe Cdc14p
      homolog, Clp1p, and show that it is not required for mitotic exit but rather
      functions together with the SIN in coordinating cytokinesis with the nuclear
      division cycle. As cells enter mitosis, Clp1p relocalizes from the nucleolus to
      the spindle and site of cell division. Clp1p exit from the nucleolus does not
      depend on the SIN, but the SIN is required for keeping Clp1p out of the nucleolus
      until completion of cytokinesis. Clp1p, in turn, may promote the activation of
      the SIN by antagonizing Cdk activity until cytokinesis is complete and thus
      ensuring that cytokinesis is completed prior to the initiation of the next cell
      cycle. In addition to its roles in anaphase, Clp1p regulates the G2/M transition
      since cells deleted for clp1 enter mitosis precociously and cells overexpressing
      Clp1p delay mitotic entry. Unlike Cdc14p, Clp1p appears to antagonize Cdk
      activity by preventing dephosphorylation of Cdc2p on tyrosine. CONCLUSIONS: S.
      pombe Clp1p affects cell cycle progression in a markedly different manner than
      its S. cerevisiae homolog, Cdc14p. This finding raises the possibility that
      related phosphatases in animal cells will prove to have important roles in
      coordinating the onset of cytokinesis with the events of mitosis.

PMID- 11448770
TI  - Novel small RNA-encoding genes in the intergenic regions of Escherichia coli.
AB  - BACKGROUND: Small, untranslated RNA molecules were identified initially in
      bacteria, but examples can be found in all kingdoms of life. These RNAs carry out
      diverse functions, and many of them are regulators of gene expression. Genes
      encoding small, untranslated RNAs are difficult to detect experimentally or to
      predict by traditional sequence analysis approaches. Thus, in spite of the rising
      recognition that such RNAs may play key roles in bacterial physiology, many of
      the small RNAs known to date were discovered fortuitously. RESULTS: To search the
      Escherichia coli genome sequence for genes encoding small RNAs, we developed a
      computational strategy employing transcription signals and genomic features of
      the known small RNA-encoding genes. The search, for which we used rather
      restrictive criteria, has led to the prediction of 24 putative sRNA-encoding
      genes, of which 23 were tested experimentally. Here we report on the discovery of
      14 genes encoding novel small RNAs in E. coli and their expression patterns under
      a variety of physiological conditions. Most of the newly discovered RNAs are
      abundant. Interestingly, the expression level of a significant number of these
      RNAs increases upon entry into stationary phase. CONCLUSIONS: Based on our
      results, we conclude that small RNAs are much more widespread than previously
      imagined and that these versatile molecules may play important roles in the fine
      tuning of cell responses to changing environments.

PMID- 11448771
TI  - Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6.
AB  - BACKGROUND: Dickkopf-1 (Dkk-1) is a head inducer secreted from the vertebrate
      head organizer and induces anterior development by antagonizing Wnt signaling.
      Although several families of secreted antagonists have been shown to inhibit Wnt
      signal transduction by binding to Wnt, the molecular mechanism of Dkk-1 action is
      unknown. The Wnt family of secreted growth factors initiates signaling via the
      Frizzled (Fz) receptor and its candidate coreceptor, LDL receptor-related protein
      6 (LRP6), presumably through Fz-LRP6 complex formation induced by Wnt. The
      significance of the Fz-LRP6 complex in signal transduction remains to be
      established. RESULTS: We report that Dkk-1 is a high-affinity ligand for LRP6 and
      inhibits Wnt signaling by preventing Fz-LRP6 complex formation induced by Wnt.
      Dkk-1 binds neither Wnt nor Fz, nor does it affect Wnt-Fz interaction. Dkk-1
      function in head induction and Wnt signaling inhibition strictly correlates with
      its ability to bind LRP6 and to disrupt the Fz-LRP6 association. LRP6 function
      and Dkk-1 inhibition appear to be specific for the Wnt/Fz beta-catenin pathway.
      CONCLUSIONS: Our results demonstrate that Dkk-1 is an LRP6 ligand and inhibits
      Wnt signaling by blocking Wnt-induced Fz-LRP6 complex formation. Our findings
      thus reveal a novel mechanism for Wnt signal modulation. LRP6 is a Wnt coreceptor
      that appears to specify Wnt/Fz signaling to the beta-catenin pathway, and Dkk-1,
      distinct from Wnt binding antagonists, may be a specific inhibitor for Wnt/beta
      catenin signaling. Our findings suggest that Wnt-Fz-LRP6 complex formation, but
      not Wnt-Fz interaction, triggers Wnt/beta-catenin signaling.

PMID- 11448772
TI  - Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires
      NBS and telomerase catalytic subunit.
AB  - Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome
      instability, radiosensitivity, cancer predisposition, immunodeficiency, and other
      defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA repair complex [3
      5] and is localized to telomere ends in association with TRF proteins [6, 7]. We
      show that blood cells from NBS patients have shortened telomere DNA ends.
      Likewise, cultured NBS fibroblasts that exhibit a premature growth cessation were
      observed with correspondingly shortened telomeres. Introduction of the catalytic
      subunit of telomerase, TERT, was alone sufficient to increase the proliferative
      capacity of NBS fibroblasts. However, NBS, but not TERT, restores the capacity of
      NBS cells to survive gamma irradiation damage. Strikingly, NBS promotes telomere
      elongation in conjunction with TERT in NBS fibroblasts. These results suggest
      that NBS is a required accessory protein for telomere extension. Since NBS
      patients have shortened telomeres, these defects may contribute to the chromosome
      instability and disease associated with NBS patients.

PMID- 11448773
TI  - Hsp70 sequences indicate that choanoflagellates are closely related to animals.
AB  - Over 130 years ago, James-Clark noted a remarkable structural similarity between
      the feeding cells of sponges (choanocytes) and a group of free-living protists,
      the choanoflagellates. Both cell types possess a single flagellum surrounded by a
      collar of fine tentacles. The similarity led to the hypothesis that sponges, and,
      by implication, other animals, evolved from choanoflagellate-like ancestors.
      Phylogenetic analysis of ribosomal DNA neither supports nor refutes this
      hypothesis. Here, we report the sequence of an hsp70 gene and pseudogene from the
      freshwater choanoflagellate Monosiga ovata. These represent the first nuclear
      encoded protein-coding sequences reported for any choanoflagellate. We find that
      Monosiga and most bilaterian hsp70 genes have high GC contents that may distort
      phylogenetic tree construction; therefore, protein sequences were used for
      phylogenetic reconstruction. Our analyses indicate that Monosiga is more closely
      related to animals than to fungi. We infer that animals and at least some
      choanoflagellates are part of a clade that excludes the fungi. This is consistent
      with the origin of animals from a choanoflagellate-like ancestor.

PMID- 11448774
TI  - Why do birds sleep with one eye open? Light exposure of the chick embryo as a
      determinant of monocular sleep.
AB  - Together with some aquatic mammals, birds exhibit a unique behavioral and
      electrophysiological state called "unihemispheric sleep," in which one cerebral
      hemisphere is awake and the other is sleeping. Slow-wave sleep in one hemisphere
      is associated with closure of the contralateral eye, while the eye contralateral
      to the awake hemisphere is open; closure of both eyes, in contrast, is associated
      with bihemispheric slow-wave sleep or with REM sleep. During the last few days of
      incubation, the chick's embryo is turned in the egg so that it occludes its left
      eye, whereas light entering through the shell can stimulate the right eye. Here
      we show that in the first two days after hatching, chicks coming from eggs
      incubated in the light prevalently slept with their right eye open, whereas those
      coming from eggs incubated in the dark prevalently slept with their left eye
      open. Thus, asymmetric light stimulation in the embryo can modulate the left
      right direction of eye opening during post-hatching monocular sleep.

PMID- 11448775
TI  - Links between vision and somatosensation. Vision can improve the felt position of
      the unseen hand.
AB  - During reaching movements, sensory signals must be transformed into appropriate
      motor commands. Anatomical, electrophysiological, and neuropsychological evidence
      suggest that there is no single, supramodal map of space that is used to guide
      reaching. Instead, movements appear to be planned and controlled within multiple
      coordinate systems, each one attached to a different body part. Recent
      neuropsychological investigations demonstrating that somatosensory impairments
      can be ameliorated by visual cues, and visual impairments by proprioceptive cues,
      have been interpreted as evidence that arm-centered representations may exist in
      humans. A critical difference between the findings obtained in the monkey and in
      humans, however, is that in the latter case, vision of the limb appears be
      critical for visual somatosensory binding. Here, we report a case study of a
      patient (C.T.) recovering from unilateral somatosensory impairment, including
      tactile extinction, who executed reaches toward visually defined or
      proprioceptively defined locations. We demonstrate that when the target location
      of a reach was defined proprioceptively, by passively positioning our patient's
      impaired hand beneath the table surface, vision of the workspace immediately
      adjacent to the unseen hand dramatically increased the endpoint accuracy of her
      reaching movements, even though such cues could not possibly signal the position
      of the target directly.

PMID- 11448776
TI  - CAPRI regulates Ca(2+)-dependent inactivation of the Ras-MAPK pathway.
AB  - Ca(2+) is a universal second messenger that is critical for cell growth and is
      intimately associated with many Ras-dependent cellular processes such as
      proliferation and differentiation. Ras is a small GTP binding protein that
      operates as a molecular switch regulating the control of gene expression, cell
      growth, and differentiation through a pathway from receptors to mitogen-activated
      protein kinases (MAPKs). A role for intracellular Ca(2+) in the activation of Ras
      has been previously demonstrated, e.g., via the nonreceptor tyrosine kinase PYK2
      and by Ca(2+)/calmodulin-dependent guanine nucleotide exchange factors (GEFs)
      such as Ras-GRF; however, there is no Ca(2+)-dependent mechanism for direct
      inactivation. An important advance toward greater understanding of the complex
      coordination within the Ras-signaling network is the spatio-temporal analysis of
      signaling events in vivo. Here, we describe the identification of CAPRI (Ca(2+)
      promoted Ras inactivator), a Ca(2+)-dependent Ras GTPase-activating protein (GAP)
      that switches off the Ras-MAPK pathway following a stimulus that elevates
      intracellular Ca(2+). Analysis of the spatio-temporal dynamics of CAPRI indicates
      that Ca(2+) regulates the GAP by a fast C2 domain-dependent translocation
      mechanism.

PMID- 11448777
TI  - NAADP receptors are present and functional in the heart.
AB  - Alongside the well-studied inositol 1,4,5 trisphosphate and ryanodine receptors,
      evidence is gathering that a new intracellular release mechanism, gated by the
      pyridine nucleotide nicotinic acid adenine dinucleotide phosphate (NAADP), is
      present in numerous organisms, ranging from plant to mammalian cells (reviewed in
      [1]). Most cells have been shown to express at least two Ca(2+)-release
      mechanisms controlled by different messengers, and this can lead to redundancy,
      convergence, or divergence of responses. One exception appears to be muscle and
      heart contractile tissues. Here, it is thought that the dominant intracellular
      channel is the ryanodine receptor, while IP(3) receptors are poorly expressed and
      their role appears to be negligible. We now report that NAADP receptors are
      functional and abundant in cardiac microsomes. NAADP binds specifically and with
      high affinity (130 pM and 4 nM) to two sites on cardiac microsomes and releases
      Ca(2+) with an apparent EC(50) of 323 +/- 14 nM. Furthermore, binding experiments
      show that this receptor displays both positive and negative cooperativity, a
      peculiarity unique among intracellular Ca(2+) channels. Therefore, we show that
      the heart possesses multiple mechanisms to increase the complexity of Ca(2+)
      signaling and that NAADP may be integral in the functioning of this organ.

PMID- 11448778
TI  - Sister chromatid cohesion is required for postreplicative double-strand break
      repair in Saccharomyces cerevisiae.
AB  - The repair of DNA double-strand breaks by recombination requires the presence of
      an undamaged copy that is used as a template during the repair process. Because
      cells acquire resistance to gamma irradiation during DNA replication and because
      sister chromatids are the preferred partner for double-strand break repair in
      mitotic diploid yeast cells, it has long been suspected that cohesion between
      sister chromatids might be crucial for efficient repair. This hypothesis is
      consistent with the sensitivity to gamma irradiation of mutants defective in the
      cohesin complex that holds sister chromatids together from DNA replication until
      the onset of anaphase (reviewed in) . It is also in accordance with the finding
      that surveillance mechanisms (checkpoints) that sense DNA damage arrest cell
      cycle progression in yeast by causing stabilization of the securin Pds1, thereby
      blocking sister chromatid separation. The hypersensitivity to irradiation of
      cohesin mutants could, however, be due to a more direct involvement of the
      cohesin complex in the process of DNA repair. We show here that passage through S
      phase in the presence of cohesin, and not cohesin per se, is essential for
      efficient double-strand break repair during G2 in yeast. Proteins needed to load
      cohesin onto chromosomes (Scc2) and to generate cohesion during S phase (Eco1)
      are also shown to be required for repair. Our results confirm what has long been
      suspected but never proven, that cohesion between sister chromatids is essential
      for efficient double-strand break repair in mitotic cells.

PMID- 11448779
TI  - Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the
      nuclear receptor coactivator PRMT1.
AB  - Posttranslational modifications of histone amino termini play an important role
      in modulating chromatin structure and function. Lysine methylation of histones
      has been well documented, and recently this modification has been linked to
      cellular processes involving gene transcription and heterochromatin assembly.
      However, the existence of arginine methylation on histones has remained unclear.
      Recent discoveries of protein arginine methyltransferases, CARM1 and PRMT1, as
      transcriptional coactivators for nuclear receptors suggest that histones may be
      physiological targets of these enzymes as part of a poorly defined
      transcriptional activation pathway. Here we show by using mass spectrometry that
      histone H4, isolated from asynchronously growing human 293T cells, is methylated
      at arginine 3 (Arg-3) in vivo. In support, a novel antibody directed against
      histone H4 methylated at Arg-3 independently demonstrates the in vivo occurrence
      of this modification and reveals that H4 Arg-3 methylation is highly conserved
      throughout eukaryotes. Finally, we show that PRMT1 is the major, if not
      exclusive, H4 Arg-3 methyltransfase in human 293T cells. These findings suggest a
      role for arginine methylation of histones in the transcription process.

PMID- 11448780
TI  - Bold call for more GM animals.

PMID- 11448781
TI  - Putting cells together again.
AB  - Computational biologists are trying to combine the pieces of knowledge about the
      cell to develop a bigger picture. Such a 'virtual cell' is proving useful for the
      simulation of cellular processes, reports Michael Gross.

PMID- 11448782
TI  - Centromeres.

PMID- 11448783
TI  - Non-homologous end joining as a mechanism of DNA repair.

PMID- 11448784
TI  - An ancestral whole-genome duplication may not have been responsible for the
      abundance of duplicated fish genes.

PMID- 11448785
TI  - Membrane traffic: how do GGAs fit in with the adaptors?
AB  - The AP-1 adaptor complex has been cast as the major player in clathrin coat
      formation for vesicular transport from the trans-Golgi to the endocytic pathway.
      But new results on 'GGA' proteins have raised doubts about this paradigm and
      suggest both a new sorting mechanism and an unexpected complexity in the roles of
      clathrin.

PMID- 11448786
TI  - Cystic fibrosis: the 'bicarbonate before chloride' hypothesis.
AB  - The specific effects of some mutations that cause cystic fibrosis suggest that
      reduced HCO(3)(-) transport is the key to understanding cystic fibrosis
      pathology. But there is a puzzling discrepancy between measures of CFTR-mediated
      chloride conductance in expression systems and the sweat chloride values of
      patients.

PMID- 11448787
TI  - Cell cycle: how, when and why cells get rid of cyclin A.
AB  - Sequences outside the 'destruction box' direct the degradation of cyclin A to
      completion before the metaphase-anaphase transition; cyclin A that escapes timely
      degradation can block the metaphase-anaphase transition, impede anaphase and
      telophase, and impair a cell's ability to arrest in G1 of the next cell cycle.

PMID- 11448788
TI  - Vertebrate gastrulation: calcium waves orchestrate cell movements.
AB  - A recent study reveals that the propagation of intercellular calcium signals is
      closely associated with the generation of convergent extension movements during
      Xenopus gastrulation. Such signals provide a mechanism whereby large populations
      of cells can communicate to generate orchestrated cell movements.

PMID- 11448789
TI  - Behavioral genetics: anxiety under interrogation.
AB  - Recent genetic mapping experiments in the mouse have made significant inroads
      into understanding the complex genetics of behavior and, in particular, anxiety.

PMID- 11448790
TI  - Cytoskeleton: CLASPing the end to the edge.
AB  - Microtubules play a critical role in establishing asymmetry in many cell types.
      Recent work suggests how conserved protein complexes that bind specifically to
      the growing ends of microtubules may establish polarized links to special regions
      of the cell cortex.

PMID- 11448791
TI  - Gonad development: signals for sex.
AB  - The formation of testes or ovaries in the mammalian embryo is critical in
      determining sexual identity and the ability to reproduce. Recent studies have
      begun to illuminate the cellular signalling events required for development of
      functional testes.

PMID- 11448792
TI  - Stem cells: so what's in a niche?
AB  - Much effort is being invested in defining the intrinsic and extrinsic factors
      that control stem cell maintenance and proliferation. Recent studies have
      identified a signaling hierarchy involved in coordinating the proliferation of
      germ line and somatic stem cells in the Drosophila ovary.

PMID- 11448793
TI  - Centrioles take center stage.
AB  - Centrioles are among the most beautiful and mysterious of all cell organelles.
      Although the ultrastructure of centrioles has been studied in great detail ever
      since the advent of electron microscopy, these studies raised as many questions
      as they answered, and for a long time both the function and mode of duplication
      of centrioles remained controversial. It is now clear that centrioles play an
      important role in cell division, although cells have backup mechanisms for
      dividing if centrioles are missing. The recent identification of proteins
      comprising the different ultrastructural features of centrioles has proven that
      these are not just figments of the imagination but distinct components of a large
      and complex protein machine. Finally, genetic and biochemical studies have begun
      to identify the signals that regulate centriole duplication and coordinate the
      centriole cycle with the cell cycle.

PMID- 11448794
TI  - Predictability and other aspects of post-transplant diabetes mellitus in heart
      transplant recipients.
AB  - BACKGROUND: Diabetes mellitus that develops after organ transplantation may
      predispose patients to further complications. We studied the value of pre
      transplant oral glucose tolerance testing or maximum random plasma glucose, and
      HLA-DR3 and/or DR4 phenotype as predictors of post-transplantation diabetes
      mellitus in heart transplant recipients. PATIENTS AND METHODS: In 228 cardiac
      allograft recipients (median age, 50 years; mean follow-up, 4.77 years), we used
      either pre-transplant oral glucose tolerance testing results (Group I, n = 141)
      excluding patients with pre-existing diabetes (n = 9)--or maximum random plasma
      glucose values (Group II, n = 78) to study predictability of post-transplant
      diabetes. In addition, we investigated its relation to rejection treatment and
      clinical course. RESULTS: Cumulative incidence of post-transplant diabetes (n =
      43) was 19.6%, 83% of which became manifest within 3 months post-transplant; pre
      transplant body mass index was higher (p < 0.01) in this group. Mortality did not
      increase. Of 123 patients in Group I who survived > 3 months, post-transplant
      diabetes occurred in 32% vs 16% of those with impaired and normal glucose
      tolerance respectively (ns), and in 55% of patients with isolated post-load
      hyperglycemia (p < 0.05 vs normal). Maximum random glucose values (Group II) did
      not predict post-transplant diabetes. Prevalence of the HLA-DR3, DR4, and DR3DR4
      phenotypes did not increase in post-transplant diabetes; relation to rejection
      treatment was likely in 30%. Approximately 50% of posttransplant diabetes
      patients required only temporary drug treatment. CONCLUSIONS: The risk of post
      transplant diabetes increased parallel to pre-transplant degree of glucose
      intolerance, but was considerable even in normal glucose tolerance. HLA-DR3
      and/or DR4 phenotype was not a predisposing factor.

PMID- 11448795
TI  - Severe tricuspid regurgitation after heart transplantation.
AB  - BACKGROUND: Tricuspid regurgitation (TR) is common after heart transplantation.
      However, the incidence of severe TR and the incidence of symptoms after
      echocardiographic diagnosis of severe TR have not been documented. The purpose of
      this study is to determine the incidence of severe TR and its clinical
      significance in the heart transplant population. METHODS: We reviewed
      echocardiograms (echo) of all heart transplant patients coming for regular
      echocardiographic follow-up between 1990 and 1995. We reviewed the charts of all
      patients who had echo diagnosis of severe TR. RESULTS: A total of 336 patients
      had echo follow-up during this time period. The number of months post-heart
      transplant to last echo was 54 +/- 50 (range, 1 to 265 months). Ninety patients
      had moderate TR and 23 patients had severe TR. Mean time from heart
      transplantation to diagnosis of severe TR was 43 +/- 38 months (range, 1 to 132).
      Using Cutler-Ederer analysis, at 5 years, 92.2% of surviving patients were free
      from severe TR. At 10 years, 85.8% of surviving patients were free from severe
      TR. Of the 23 patients with severe TR, 17 had charts available for review. The
      mean number of prior endomyocardial biopsies was 28 +/- 21 (range, 3 to 88).
      These patients were followed for 35 +/- 18 months after diagnosis. During this
      period, they developed significant heart failure and peripheral edema. Six
      patients eventually underwent tricuspid valve replacement. CONCLUSIONS: Moderate
      to severe TR commonly occurs following heart transplantation. Severe TR is
      associated with significant morbidity.

PMID- 11448796
TI  - HBV and HCV infections in heart transplant recipients.
AB  - BACKGROUND: Heart transplant (HTx) recipients risk acquiring hepatotropic viral
      infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), and the
      impact of these infections on post-HTx survival remains unclear. The aim of the
      present study was to define the prevalence, clinical features, and natural
      history of HBV and HCV infections in a cohort of HTx recipients. METHODS: We
      retrospectively studied 360 consecutive patients who had undergone HTx. Clinical
      picture, hepatic injury indexes, and HBV/HCV viral serology were followed post
      transplant. RESULTS: During follow-up (average, 8 +/- 3.1 years), 49 (16.5%) of
      the HTx recipients tested positive for at least 1 of the 2 viruses (3.1% HBV, 12%
      HCV, 0.5% concomitant infection). The prevalence of HCV infection in heart
      transplant recipients transplanted before and after 1990 was 28% and 4.2%,
      respectively, the latter being markedly lower (p < 0.001) than in earlier series
      of HTx recipients and much lower than expected in the age- and sex-matched
      general population. All HBV-positive and 58% of HCV-positive recipients developed
      chronic liver disease. Sixteen percent of patients developed cirrhosis during
      follow-up, and 8% died of end-stage liver disease. CONCLUSIONS: The prevalence of
      HBV and HCV in a large population of HTx recipients is not very different from
      that reported in the general population. Active viral replication of HBV and an
      aggressive natural history of both infections are seen in HTx recipients,
      however. The low prevalence of HBV- and HCV-related infection in recent series
      probably reflects current viral screening and vaccination policies.

PMID- 11448797
TI  - Advanced medical therapy does not render heart transplantation obsolete for
      ambulatory end-stage heart failure patients: a debate.

PMID- 11448798
TI  - Surgical alternatives for heart failure.
AB  - Heart failure is one of the leading causes of hospitalization in the United
      States. Congestive heart failure is a chronic, progressive disease and its
      central element is remodeling of the cardiac chamber associated with ventricular
      dilation. Secondary mitral regurgitation is a complication of end-stage
      cardiomyopathy and is associated with poor prognosis. Historically, these
      patients were not considered operative candidates because of their high morbidity
      and mortality. Heart transplantation is now considered standard treatment for
      select patients with end-stage heart disease; however, it is applicable only to a
      small number of patients. In an effort to address this problem, newer and
      alternative surgical approaches are evolving, including mitral valve
      annuloplasty, the Batista procedure, and other left ventricular shape changing
      technologies. Using these operative techniques to alter the shape of the left
      ventricle, in combination with optimal medical management for heart failure,
      improves survival, and patients may avoid or postpone transplantation.

PMID- 11448799
TI  - Suggested guidelines for the use of tacrolimus in cardiac transplant recipients.

PMID- 11448800
TI  - Lung transplantation for emphysema: two lungs or one.

PMID- 11448801
TI  - Homocysteine--a treatable risk factor for allograft vascular disease after heart
      transplantation?
AB  - Growing evidence suggests that elevated total plasma homocysteine (tHCY) levels
      are associated with cardiac allograft vasculopathy following heart
      transplantation. To assess the effect of folic acid supplementation on tHCY
      levels, we performed a prospective study in a cohort of 69 patients (7.0 +/- 3.2
      years after heart transplantation; mean age, 55.0 +/- 9.6 years; 61 male) treated
      with 5 mg folic acid/day (n = 34) vs no medication (n = 35). Therapy with folic
      acid resulted in significantly decreased tHCY levels, from 22.6 +/- 9.6
      micromol/liter to 17.3 +/- 5.5 micromol/liter (p = 0.001) within 3 months,
      whereas values in the control group remained unchanged. We conclude that folic
      acid supplementation (5 mg per day) provides a simple and effective measure to
      lower elevated tHCY levels in heart transplant recipients.

PMID- 11448802
TI  - The 4-amino analogue of tetrahydrobiopterin efficiently prolongs murine cardiac
      allograft survival.
AB  - We tested the 4-amino analogue of tetrahydrobiopterin (H(4)aminobiopterin), a
      novel pterin-based inhibitor of nitric oxide synthases, for its efficacy in a
      murine cardiac-transplant model employing an improved cuff technique. We treated
      groups of 5 animals each for the first 7 post-operative days with various doses
      of H(4)aminobiopterin, with Cyclosporin A (15 mg/kg/day), or no treatment.
      H(4)aminobiopterin (3 times 50 mg/kg/day) proved to be as efficient as high-dose
      Cyclosporin A (15 mg/kg/day) in prolonging allograft survival and in suppressing
      histologic changes caused by the immunoreaction. Surprisingly, the doses of
      H(4)aminobiopterin effective in prolonging allograft survival did not change the
      plasma nitrite plus nitrate, or the expression of inducible nitric oxide
      synthase, interferon-gamma, tumor necrosis factor-alpha, and B7-1 (CD80),
      indicating that H(4)aminobiopterin may act through a novel, yet undiscovered
      mechanism.

PMID- 11448803
TI  - Intra-aortic balloon pumping in children with dilated cardiomyopathy as a bridge
      to transplantation.
AB  - Children with dilated cardiomyopathy awaiting transplantation who fail maximal
      pharmacologic therapy may benefit from intra-aortic balloon pumping. Between July
      1993 and August 1999, a total of 4 children with dilated cardiomyopathy underwent
      pre-transplant balloon pumping for 6.0 +/- 5.8 (1 to 12) days. One child (pumped
      for 12 days) died awaiting transplant, and the remaining 3 were successfully
      transplanted. Intra-aortic balloon pumping timed precisely with M-mode
      echocardiographic markers offers a relatively simple and safe intermediate level
      of mechanical support for children with dilated cardiomyopathy who fail
      pharmacologic support.

PMID- 11448804
TI  - Association of parvovirus B19 with plasma cell-rich myocardial infiltrates after
      heart transplantation.
AB  - In this report we describe the development of plasma cell-rich myocardial
      infiltrates in association with a parvovirus B19 infection in a heart transplant
      patient. We hypothesize that the virus, either alone or in association with the
      cardiac allograft, may polarize the immune response in the direction of T helper
      2 (Th2) cells rather than the expected Th1 cells. This favors the development of
      a humoral immune response and infiltration of the graft with plasma cells.

PMID- 11448805
TI  - Hypotensive reactions associated with transfusion of bedside leukocyte-reduction
      filtered blood products in heart transplanted patients.
AB  - Severe hypotensive reactions that occur during transfusions of blood products to
      non-transplanted patients were recently linked to the use of bedside leukocyte
      reduction filters, sometimes in association with angiotensin-converting enzyme
      (ACE) inhibitor treatment. We present the first report of such reactions in
      patients who underwent orthotopic heart transplantation. Fourteen (47%) of the 30
      transfused patients experienced severe hypotensive reaction during filtered
      transfusion of at least 1 unit of blood product, with a total of 24 episodes.
      Eleven (79%) of these patients were treated pre-operatively with ACE inhibitors.

PMID- 11448806
TI  - A technique of heterotopic, infrarenal heart transplantation with double
      anastomosis in mice.
AB  - Mouse heart transplantation is frequently used to investigate mechanisms of
      rejection and immune response. A fully vascularized technique is presented in
      which the graft ascending aorta is anastomosed end-to-side to the recipient's
      aorta and the pulmonary aorta is anastomosed end-to-side to the inferior vena
      cava using 11-0 Ethilon suture. We suggest that this double anastomosis technique
      is a valuable tool to investigate immune mechanisms in mice.

PMID- 11448807
TI  - Educational needs of patients with advanced heart failure and their caregivers.
AB  - At the time of initial transplant evaluation, we evaluated the information and
      counseling needs of 82 outpatients with advanced heart failure and compared them
      with the needs of 74 of their caregivers. Both groups answered a 23-item
      questionnaire, which used a 5-point Likert scale to assess needs across 6 sub
      scales specific to heart failure and the process of determining transplant
      eligibility. The 5 most important learning needs of patients and caregivers were
      similar, and we found significant differences only in the groups' responses to 3
      individual questions. We conclude that nurses can meet the needs of patients and
      their caregivers by providing honest explanations, focusing on enhanced quality
      of life issues, and giving information for dealing with an emergency.

PMID- 11448808
TI  - Treatment of post-transplant lymphoproliferative disorder with monoclonal CD20
      antibody (rituximab) after heart transplantation.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a frequent and often fatal
      complication of organ transplantation. It most often results from an Epstein-Barr
      virus (EBV)-transformed B-cell clone, which expresses B-cell surface markers such
      as CD20. We describe a case of a heart transplant recipient who EBV seroconverted
      post-transplant and subsequently developed subcutaneous and lymphatic B-cell
      lymphoma, successfully treated with CD20 antibody (rituximab). The patient has
      been in remission during 10 months of clinical follow-up.

PMID- 11448809
TI  - Pheochromocytoma presenting after cardiac transplantation for dilated
      cardiomyopathy.
AB  - Pheochromocytoma may present with a clinical picture indistinguishable from that
      of idiopathic dilated cardiomyopathy. We report 2 such patients who underwent
      cardiac transplantation following which we diagnosed and successfully treated
      pheochromocytoma.

PMID- 11448810
TI  - Unprotected left main coronary artery stenting for cardiac allograft
      vasculopathy.
AB  - Cardiac allograft vasculopathy is the leading cause of death after the first year
      of transplantation. Treatment outcomes with medication, balloon angioplasty,
      bypass surgery, and retransplantation have been disappointing. We present our
      initial experience with stenting of the left main coronary artery in the setting
      of allograft vasculopathy.

PMID- 11448811
TI  - Cardiomyopathy in a carrier of Duchenne's muscular dystrophy.
AB  - During the third trimester of her pregnancy, a 25-year-old carrier of Duchenne's
      muscular dystrophy developed severe cardiac failure and required mechanical
      circulatory support and transplantation. Her cardiac function improved during 311
      days of circulatory support. However this improvement was not sufficient to allow
      removal of her left ventricular assist device before transplantation.

PMID- 11448812
TI  - Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric
      cardiac transplant candidate prior to transplantation.
AB  - Pulmonary hypertension represents a significant risk factor for peri-operative
      death in patients undergoing cardiac transplantation. Heart-lung transplantation
      is generally the only procedure available for patients whose pulmonary
      hypertension can not be reversed by conventional pharmacologic means. We present
      a pediatric patient with end-stage cardiac disease and refractory pulmonary
      hypertension who was treated with long-term intravenous prostacyclin. This
      resulted in a significant enough improvement in her hemodynamics to allow for
      successful cardiac transplantation alone.

PMID- 11448813
TI  - Nocardia asteroides abscess after heart transplantation.
AB  - We describe a patient who developed a primary, thigh adductor-muscle abscess
      caused by Nocardia asteroides 3 years after orthotopic cardiac transplantation.
      Nocardia was diagnosed by microbiologic culture and responded fully to a
      prolonged course of cotrimoxazole. The patient remains free of local or systemic
      disease at 2 years follow-up.

PMID- 11448814
TI  - Vascular brachytherapy for treatment of cardiac allograft vasculopathy.
AB  - A high restenosis rate often follows treatment of coronary stenoses in cardiac
      allograft vasculopathy. We report successful coronary brachytherapy of a second
      in-stent restenosis in a patient after heart transplantation.

PMID- 11448816
TI  - Knowledge growth in medical education.

PMID- 11448817
TI  - Empathy in medical education and patient care.

PMID- 11448818
TI  - Knitting.

PMID- 11448819
TI  - Emergency department overcrowding: a national crisis.

PMID- 11448820
TI  - The trials, tribulations, and relative success of the ongoing clinical merger of
      two large academic hospital systems.
AB  - The North Shore Health System and the Long Island Jewish Medical Center merged in
      1997 and now form the third largest not-for-profit academic health care system in
      the United States. The authors analyze the specific factors responsible for the
      relative success of the clinical merger, review their merger's initial failures
      and how they crafted a more pragmatic and appropriate set of guiding principles
      to continue the merger, and discuss the future of their institution's clinical
      integration strategy. In 2000, clinical integration of the 19 clinical
      departments at the two merged institutions was surveyed across five broad areas:
      conferences, residency programs, common faculty and support staff, finances, and
      research. Extents of clinical integration ranged from 20% to 72%. Six departments
      had more than 50% clinical integration, and overall clinical integration was 42%.
      Not surprisingly, clinical integration had occurred most frequently with
      conferences (50%) and least with finances (25%). The single-chairperson model for
      department leadership has been most successful in achieving significant clinical
      integration of the formerly separate departments. The relative success of the
      clinical merger has been guided by the principle that no clinical service should
      be integrated simply for the sake of merging, but rather that integration should
      be encouraged where and when it makes sense to achieve specific program goals. In
      addition, the merger would not have proceeded without constant communication
      among the leadership and staff, flexibility in building leadership models,
      patience in having events progress over a time course that developed trust among
      the senior leaders, and the presence of a senior executive structure whose
      authority to make decisions is accepted. The most important factor for achieving
      a reasonable level of clinical integration is the ability of the clinical leaders
      to collaborate and lead the change process.

PMID- 11448821
TI  - Harvard v. Canada: the myc mouse that still squeaks in the maze of biopatent law.
AB  - The Canadian Supreme Court will soon make a decision about Harvard University's
      long-standing application for a Canadian patent on a mouse transgenic for the myc
      oncogene. That decision could reignite in North America the controversy that
      continues in Europe and elsewhere to surround the patenting of life forms. The
      tortuous steps in this 15-year patent maze are marked by the arguments about life
      patents that attended the U.S. Supreme Court's decision in Diamond v.
      Chakrabarty. This patent dispute about oil-digesting bacteria cracked open the
      door for animal patents in the United States and other countries, even though the
      legal arguments involved were based on patent applications for corn seeds and
      oysters, not mammals. The patent challenge to the Harvard mouse by the Canadian
      government now threatens to close this door in Canada. The arguments against life
      patents are commonly based on moral and religious grounds that regard the
      sanctity of life and oppose its commodification. The most compelling arguments
      for such patents are based on the benefits they deliver through commercial
      exploitation of inventions. The debate about patenting animals has been more
      heated outside North America and cacaphonic in the Third World. However, the
      Canadian debate could be amplified by the U.S. Supreme Court's recent entry on
      the biopatent stage through the side door of a new corn seed patent dispute. A
      narrow legal analysis by the Canadian Supreme Court would award the mouse patent
      to Harvard, while a policy analysis might support the government's challenge of
      the patent. Although the impact of the Harvard mouse patent process in Canada
      could be just a squeak, opponents of patenting life can mount the myc mouse to
      once again roar their opposition to animal patents. And the sound could resonate
      through the arguments about both biopatents and human cloning, with potentially
      important effects for academia, industry, and the public.

PMID- 11448822
TI  - Primary care compensation at an academic medical center: a model for the mixed
      payer environment.
AB  - The authors' academic medical center, Brigham and Women's Hospital, Boston,
      Massachusetts, developed a primary care physician (PCP) salary incentive program
      for employed academic physicians. This program, first implemented in 1999, was
      needed to meet the financial imperatives placed on the institution by managed
      care and the Balanced Budget Act of 1997; its goal was to create a set of
      incentives for PCPs that is consistent with the mission of the academic center
      and helps motivate and reward PCP's work. The program sought to simultaneously
      increase productivity while optimizing resource utilization in a mixed-payer
      environment. The salary incentive program uses work relative-value units (wRVUs)
      as the measure of productivity. In addition to productivity-derived base pay,
      bonus incentives are added for efficient medical management, quality of care,
      teaching, and seniority. The authors report that there was significant concern
      from several members of the physician staff before the plan was implemented; they
      felt that the institution's PCPs were already operating at maximum clinical
      capacity. However, after the first year of operation of this plan, there was an
      overall 20% increase in PCP productivity. Increases were observed in all PCP
      subgroups when stratified by professional experience, clinical time commitment,
      and practice location. The authors conclude that the program has succeeded in
      giving incentives for academic PCPs to achieve under the growing demands for
      revenue self-sufficiency, managed care performance, quality of care, and academic
      commitment.

PMID- 11448823
TI  - How do academic health centers value and encourage clinical research?
AB  - To investigate whether there is a misalignment of the perceived values of and
      incentives for clinical research within U.S. academic health centers (AHCs), in
      1999 the authors surveyed medical school deans, academic administrators,
      department chairs, and faculty members at 80 AHCs that are the members of the
      University HealthSystem Consortium, a not-for-profit consortium of AHCs. A total
      of 358 faculty from 58% of the institutions surveyed responded, with a mean of
      3.76 responses/institution. There was general agreement that clinical research
      offers AHCs a considerable spectrum of benefits, including prestige, recruitment
      and retention of faculty, criteria for promotion of faculty, and financial
      support. Investigator-initiated research and government-funded research ranked
      highest in terms of their desirability compared with industry-sponsored and
      contract research. This preference was agreed upon across all categories of
      respondents and types of research (translational, clinical tests, and outcomes).
      Significant differences existed between the perceptions of deans/AHC
      administrators, who stated that they were increasing their emphasis on clinical
      investigation in the areas of research space (56% of responders), administrative
      support (81%), and patient recruitment (61%) and the perceptions of their
      departmental chairs/faculties in the same areas (34%, 52%, and 40%, respectively;
      p <.05). Faculty opinions documented few new investments in the actual
      infrastructure dedicated to clinical research. The authors conclude that their
      findings, which they consider reasonably representative, strongly suggest that
      the value of clinical research to AHCs is well understood. Their findings also
      identify important opportunities for AHCs to provide a wider range of incentives
      for the conduct of clinical research.

PMID- 11448824
TI  - Why we are on the cusp of a generalist crisis.

PMID- 11448825
TI  - It's past time to reform the musculoskeletal curriculum.

PMID- 11448826
TI  - Doctor means teacher.

PMID- 11448829
TI  - The responsibilities and activities of internal medicine clerkship directors.
AB  - PURPOSE: To characterize the responsibilities, activities, and scholarly
      productivity of internal medicine clerkship directors (CDs). METHODS: In 1999,
      internal medicine CDs from 122 U.S. medical schools and one Canadian medical
      school were surveyed. The instrument asked about the CDs' demo-graphics,
      workloads, clerkship characteristics, and scholarly productivity. RESULTS: The
      response rate was 89%; 72% of the respondents were men. Mean age was 45 years,
      mean time as CD was 6.5 years, and 58% of the CDs had completed fellowship
      training. The CDs spent 28% of their professional time on the clerkship, three
      half days weekly in clinic, and three months on inpatient services. The CDs had
      published a mean of 2.2 (range 0-20) articles and received a mean of 0.7 (range 0
      4) grants. Similar factors were associated with publishing articles and receiving
      grants; gender (men), < or = three clinic half days weekly, fellowship training,
      having a faculty development program, teaching other courses, and discussing
      expectations with their department chairs. In a multivariate analysis, fellowship
      training, clinic half days, teaching other courses, and discussing expectations
      explained 22% of the variance for papers published. For grants received, a model
      with gender, clinic half days, a faculty development program, discussing
      expectations, and teaching other courses explained 35% of the variance.
      CONCLUSIONS: An internal medicine CD invests significant effort administering the
      clerkship and contributing to clinical and educational activities. The factors
      associated with successful scholarship may be useful for fostering CDs' academic
      careers.

PMID- 11448830
TI  - Prevention practices of family medicine clerkship preceptors in North Carolina.
AB  - PURPOSE: Before implementing a new prevention curriculum, the authors assessed
      the prevention practices and attitudes of community family physicians in North
      Carolina who precepted third-year family medicine clerkship students. METHOD: An
      18-item questionnaire was mailed to 165 preceptors during the 1995-96 academic
      year. The questionnaire explored the preceptors' levels of preparation to counsel
      patients, the types of prevention services they offered, and their levels of
      success in modifying patients' behaviors. The survey was re-sent to non
      respondents. RESULTS: The response rate was 70% (n = 112); of these 75% were men
      and 55% had graduated after 1987. Over 60% of the preceptors "almost always"
      offered services in smoking cessation, exercise, diet and nutrition, and age
      specific services (range 62-86%). Over 50% felt "very prepared" to counsel
      patients regarding smoking cessation, sexually transmitted diseases, depression,
      exercise, alcohol use, and age-specific services (range 53-74%). However, the
      preceptors in this study felt pessimistic about their success in getting patients
      to change their behaviors. Preceptors who had graduated more recently offered
      more preventive services for smoking cessation, alcohol use, and illicit drugs
      than did earlier graduates. DISCUSSION: Although North Carolina preceptors were
      pessimistic about their success in changing patients' behaviors regarding
      prevention, they were confident about their knowledge and skills to provide these
      services. This information was used to modify a prevention curriculum for third
      year medical students.

PMID- 11448831
TI  - A follow-up study of the characteristics of dean's letters.
AB  - PURPOSE: To assess the content and quality of dean's letters since the
      publication of guidelines recommended by the Association of American Medical
      Colleges (AAMC) in 1989. METHOD: In 1998, the dean's letter writers at all 124
      U.S. medical schools were surveyed. The questionnaire incorporated items from two
      previous surveys (1981 and 1992). In addition, samples of dean's letters (n =
      451) from all U.S. medical schools for the graduating class of 1998 were rated
      based on the AAMC's guidelines. RESULTS: The response rate of the 1998 survey
      (66%) was lower than those of the two previous surveys (87% for 1992 and 85% for
      1981). Schools that prepared letters that followed the AAMC's guidelines were
      somewhat more likely to have responded. According to the letter writers in 1998,
      close to 300,000 letters (approximately 1,050,000 pages total) were sent to
      residency directors, at an estimated cost of $26,000 per school. A total of 65%
      of schools produced adequate dean's letters based on the 1989 AAMC's guidelines,
      compared with 55% in 1992. Many schools were organizing the dean's letter in more
      readable formats, and more schools provided information that allowed for a
      comparison of students within the same school. CONCLUSION: The improvements in
      dean's letters are encouraging, but ten years after the AAMC's guidelines, 35% of
      U.S. schools still produce unacceptable letters. With the addition of the
      electronic submission of information, it is time to review further improvements
      to the dean's letter.

PMID- 11448832
TI  - Senior residents' views on the meaning of professionalism and how they learn
      about it.
AB  - PURPOSE: To determine senior residents' views on the meaning of professionalism
      and how they learned about it. METHOD: By means of a modified Dillman technique,
      all senior residents at two faculties of medicine (n = 533) were surveyed about
      professionalism during the 1998-99 academic year. The residents were asked to
      list attributes of professionalism and to rank methods they found most useful for
      learning about professionalism, to rate the adequacy and quality of their
      teaching about professionalism and their comfort in explaining the concept of
      professionalism to a more junior trainee, to list suggestions about how teaching
      about professionalism could be improved, and to name the medical organization
      most concerned with matters of professionalism. RESULTS: A total of 258 residents
      (48.4%) responded. They listed 1,052 attributes they associated with
      professionalism. The three most common attributes, all listed by more than 100
      respondents, were respect, competence, and empathy. The respondents had learned
      the most about professionalism from observing role models, they rated the
      quantity and quality of teaching about it positively, and they felt comfortable
      explaining professionalism to a junior resident. Only 56% of the residents
      correctly identified the Canadian medical organization most concerned with
      professionalism. CONCLUSION: Residents' knowledge about professionalism reflects
      their early stage of development as physicians and their daily activities, where
      such aspects of professionalism as the social contract, codes of ethics,
      participation in professional societies, and altruism are not highlighted.
      Residency programs should develop teaching activities focusing on professionalism
      that relate to issues residents face in their daily work.

PMID- 11448833
TI  - Psychosocial training in U.S. internal medicine and family practice residency
      programs.
AB  - PURPOSE: Competence in the psychosocial aspects of medical care is necessary for
      primary care physicians to function effectively. This study investigated the
      psychosocial training internal medicine and family practice residents receive in
      U.S. programs. METHODS: In 1996, program directors of all U.S. internal medicine
      (IM) and family practice (FP) residency programs were surveyed regarding the
      format, content, and quantity of psychosocial training provided in their
      programs, their opinions on topics related to psychosocial training, and
      demographics of their programs. RESULTS: The response rate was 61%. Ninety-nine
      percent of FP and 62% of IM program directors reported requiring at least one
      psychosocial training experience. Family practice programs required an average of
      352 hours (SD +/- 175; range 27-2,664) of psychosocial training compared with 118
      hours (SD +/- 272; range 0-1,050) for IM programs. Most IM and FP program
      directors expected residents to achieve at least basic competency in virtually
      all psychosocial topic areas; however, FP programs provided a greater range of
      psychosocial experiences. FP program directors most often identified
      psychologists and IM program directors most often identified internists as
      providing the most psychosocial training in their programs. Both IM and FP
      program directors considered lack of curricular time to be the main obstacle to
      development of psychosocial training. CONCLUSION: Residents' competence in
      psychosocial areas is important to both IM and FP program directors. However,
      content and time devoted to psychosocial training vary considerably both within
      and between program types.

PMID- 11448834
TI  - A multifaceted program to encourage medical students' research.
AB  - Clinician-scientists are important members of a research community that has more
      opportunities than ever before to solve problems important to patients.
      Nevertheless, the number of physicians applying for and receiving grants from the
      National Institutes of Health (NIH) has dropped. Introducing medical students to
      research and relevant support mechanisms early in their education may help to
      reverse this trend. In 1995, the Mount Sinai School of Medicine created its
      Office of Student Research Opportunities (OSRO) to stimulate students to engage
      in research. It also appointed a new dean to direct the OSRO; the person who
      filled this new position was a senior faculty member involved in patient-oriented
      research. The OSRO advises students, identifies faculty who want to mentor
      students, sponsors the Distinction in Research program, organizes an annual
      research day, helps fund summer and full-time research, and has created an
      endowment to support student travel to national meetings. Between 1997 and 2000
      the number of students who participated in the research day increased from 18 to
      74, and the number of publications by the graduating classes increased from 34 to
      58 between 1997 and 1999. Participants have presented both basic and clinical
      projects. The authors' experience has shown that medical students can be
      motivated to carry out research with appropriate encouragement from the
      administration and the faculty, something that may help to reverse a troubling
      national trend. Based upon these early successes, Mount Sinai is developing a
      novel five-year program to provide medical students with research training.

PMID- 11448835
TI  - Integrating educational objectives and the evaluation process in a general
      surgery residency program.
AB  - Although the Accreditation Council for Graduate Medical Education (ACGME)
      requires that all of its approved residency programs have written goals and
      objectives and an evaluation process, many programs have difficulty achieving
      these goals. For eight years, the general surgery residency program at Abington
      Memorial Hospital has used a system that integrates each rotation's cognitive,
      clinical, and procedural objectives into the faculty's evaluation of residents
      and residents' evaluation of the rotation. The integration of goals and
      objectives with the post-rotation evaluations provides the program with an
      ongoing and continual assessment of each resident's progress, the effectiveness
      of the faculty as teachers, and the educational value of each rotation. In this
      essay, the authors describe this integrated system and provide examples of one
      rotation's goals and objectives and the evaluation forms used by faculty and
      residents.

PMID- 11448836
TI  - Assessing the new general competencies for resident education: a model from an
      emergency medicine program.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) has promoted six
      areas that should be addressed during graduate medical training, or "general
      competencies" (GCs). According to the ACGME, these GCs should be reflected in the
      educational processes of all residency programs. In promulgating these
      competencies, however, the ACGME has not provided examples of core content,
      methods of implementation, or methods of evaluation. The authors propose a
      practical method for modifying an existing evaluation format, providing a
      template other programs could use in assessing residents' acquisition of the
      knowledge, skills, and attitudes reflected in the GCs.

PMID- 11448838
TI  - Central blockade of vasopressin V(1) receptors attenuates postexercise
      hypotension.
AB  - We tested the hypothesis that central arginine vasopressin (AVP) mediates
      postexercise reductions in arterial pressure (AP) and heart rate (HR). To test
      this hypothesis, nine spontaneously hypertensive rats (SHR) were instrumented
      with a 22-gauge stainless steel guide cannula in the right lateral cerebral
      ventricle and with a carotid arterial catheter. After the rats recovered, AP and
      HR were assessed before and after a single bout of dynamic exercise with the
      central administration of vehicle or the selective AVP V(1)-receptor antagonist
      d(CH(3))(5) Tyr(Me)-AVP (AVP-X). AP and HR were significantly decreased below
      preexercise values with central administration of vehicle [P < 0.05, change
      (Delta)-21 +/- 4 mmHg and Delta-20 +/- 6 beats/min, respectively]. In sharp
      contrast, after exercise with central administration of AVP-X, both AP (Delta+8
      +/- 5 mmHg) and HR (Delta+24 +/- 9 beats/min) were not significantly different
      from preexercise values (P > 0.05). Furthermore, AVP-X at rest did not
      significantly alter AP (181 +/- 11 vs. 178 +/- 11 mmHg, P > 0.05) or HR (328 +/-
      24 vs. 331 +/- 22 beats/min, P > 0.05). Thus central blockade of AVP V(1)
      receptors prevented postexercise reductions in AP and HR. These data suggest that
      AVP, acting within the central nervous system, mediates postexercise reductions
      in AP and HR in the SHR.

PMID- 11448839
TI  - Fetal cerebral and peripheral circulatory responses to hypoxia after nitric oxide
      synthase inhibition.
AB  - The increase in cerebral blood flow (CBF) during hypoxia in fetal sheep at 0.6
      gestation is less than the increase at 0.9 gestation when normalized for
      differences in baseline CBF and oxygen consumption. Nitric oxide (NO) synthase
      (NOS) catalytic activity increases threefold during this period of development.
      We tested the hypothesis that administration of the NOS inhibitor N(omega)-nitro
      L-arginine methyl ester (L-NAME) decreases the CBF response to systemic hypoxia
      selectively at 0.9 gestation. We also tested whether any peripheral
      vasoconstriction during hypoxia is potentiated by L-NAME at 0.9 gestation.
      Administration of L-NAME increased arterial blood pressure and decreased
      microsphere-determined CBF during normoxia in fetal sheep at both 0.6 and 0.9
      gestation. With subsequent reduction of arterial oxygen content by approximately
      50%, the percent increase in forebrain CBF in a control group (57 +/- 11%; +/-
      SE) and L-NAME-treated group (51 +/- 6%) was similar at 0.6 gestation. Likewise,
      at 0.9 gestation, the increase in CBF was similar in control (90 +/- 25%) and L
      NAME (80 +/- 28%) groups. At 0.9 gestation, L-NAME treatment attenuated the
      increase in coronary blood flow and increased gastrointestinal vascular
      resistance during hypoxia. We conclude that NO exerts a basal vasodilatory
      influence in brain as early as 0.6 gestation in fetal sheep but is not an
      important mechanism for hypoxic vasodilation in brain at either 0.6 or 0.9
      gestation. Thus the developmental increase in NOS catalytic capacity does not
      appear to be responsible for developmental increases in the CBF response to
      hypoxia during this period. In contrast, NO modulates the vascular response to
      hypoxia in heart and gastrointestinal tract.

PMID- 11448840
TI  - 2,3-Dinor-5,6-dihydro-15-F(2t)-isoprostane: a bioactive prostanoid metabolite.
AB  - 15-F(2t)-isoprostane (15-F(2t)-IsoP), also termed 8-isoprostaglandin F(2alpha),
      is one of a series of prostanoids formed by free radical-mediated peroxidation of
      arachidonic acid and exerts potent biological actions such as vasoconstriction.
      We recently demonstrated that 15-F(2t)-IsoP is metabolized in humans to a major
      metabolite, 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (15-F(2t)-IsoP-M). 15-F(2t)-IsoP
      M can also potentially be formed as a product of free radical-induced oxidation
      of the low abundance fatty acid gamma-linolenic acid. We confirmed that 15-F(2t)
      IsoP-M is generated during oxidation of gamma-linolenic acid and explored whether
      it may exhibit biological activity. 15-F(2t)-IsoP-M caused marked constriction of
      porcine surface retinal and intraparenchymal brain microvessels, comparable to
      that observed with 15-F(2t)-IsoP. These effects were associated with increased
      thromboxane A(2) (TXA(2)) formation and were virtually abolished by TXA(2)
      synthase and -receptor inhibitors (CGS-12970 and L-670596). Vasoconstriction
      induced by either 15-F(2t)-IsoP or 15-F(2t)-IsoP-M on perfused ocular choroid was
      also abrogated by TXA(2)-synthase inhibition as well as by removal of
      endothelium. Similar to 15-F(2t)-IsoP, 15-F(2t)-IsoP-M evoked vasoconstriction
      and TXA(2) generation by activating Ca(2+) influx from nonvoltage-gated channels
      (SK&F96365 sensitive) in the retina and from both nonvoltage- and N-type voltage
      gated Ca(2+) channels (omega-conotoxin MVIIA sensitive), respectively, in brain
      endothelial and astroglial cells; smooth muscle cells were unresponsive to both
      agents. Cross-desensitization experiments further suggest that 15-F(2t)-IsoP and
      15-F(2t)-IsoP-M act on the same receptor mechanism. Findings reveal a novel
      concept by which a beta-oxidation metabolite of 15-F(2t)-IsoP that can also be
      formed by nonenzymatic oxidation of gamma-linolenic acid is equivalently
      bioactive to 15-F(2t)-IsoP and may prolong the vascular actions of F(2)-IsoPs.

PMID- 11448841
TI  - Ontogeny of humoral heart rate regulation in the embryonic mouse.
AB  - Catecholamines, acetylcholine, and adenosine are known to influence cardiac
      function, yet the effects of these agents on mammalian embryonic myocardium are
      largely unknown. To address this issue, we compared the chronotrophic effects of
      adenosinergic, adrenergic, and muscarinic agents on cultured murine embryos from
      postcoital day (PC) 8.0, when the fusing heart tubes first begin to beat, to PC
      14, when cardiogenesis is essentially complete. At PC 8.0 and older, A(1)
      adenosine receptor (A(1)AR) activation significantly decreased heart rates.
      Adrenergic stimulation caused modest increases in heart rates (145-155% of
      baseline) beginning at PC 9.0. Muscarinic activation decreased heart rates only
      after PC 13. When receptor gene expression was examined, A(1)ARs and beta(1)ARs
      were expressed in isolated hearts as early as PC 9.0, and beta(2)ARs and m(2)
      muscarinic receptor genes were expressed at PC 11.0. These results identify the
      adenosinergic system as the earliest and most potent regulator of embryonic
      cardiac function and show that prenatal responsiveness to catecholamines and
      acetylcholine develops at later embryonic stages.

PMID- 11448842
TI  - Altered phosphorylation and calcium sensitivity of cardiac myofibrillar proteins
      during sepsis.
AB  - Altered phosphorylation and Ca(2+) sensitivity of cardiac myofibrillar proteins
      during different phases of sepsis were investigated. Sepsis was induced by cecal
      ligation and puncture (CLP). The results show that phosphorylation of troponin I
      (TnI) was increased by 268% during the early phase (9 h after CLP) but decreased
      by 46% during the late phase (18 h after CLP) of sepsis. Phosphorylation of C
      protein was increased by 76% during the early phase but decreased by 41% during
      the late phase of sepsis. Phosphorylation of myosin light chain-2 (MLC-2)
      remained unaltered during the early phase but was decreased by 38% during the
      late phase of sepsis. Phosphorylation of TnT was unaffected during the
      progression of sepsis. The increases in the phosphorylation of TnI and C protein
      during early sepsis were associated with the decrease in the Ca(2+) sensitivity
      of myofilaments and the increases in myocardial changes in tension development
      (+dP/dt(max)) and cAMP level. The decreases in the phosphorylation of TnI and C
      protein during late sepsis coincided with the declines in the activities of
      myofibrillar ATPase, Ca(2+) sensitivity of myofilaments, myocardial +/
      dP/dt(max), and cAMP content. The increases and the decreases in the
      phosphorylation of TnI and C protein, +/-dP/dt(max), and the tissue cAMP level
      were sensitive to isoproterenol stimulation and propranolol inhibition. These
      findings suggest that alterations in the phosphorylation of myofibrillar
      proteins, such as TnI, C protein, and MLC-2, and changes in the activities and
      the Ca(2+) sensitivity of myofibrillar ATPase may contribute to the altered
      cardiac function during the progression of sepsis. Furthermore, the sepsis
      induced alterations in the phosphorylation and Ca(2+) sensitivity of cardiac
      myofibrillar proteins were mediated via a beta-adrenergic receptor pathway.

PMID- 11448843
TI  - Increased blood pressure responses in neuropeptide Y transgenic rats.
AB  - Considering the coexistence of neuropeptide Y (NPY) and norepinephrine in
      perivascular sympathetic nerves and the known vasoconstrictor cooperation of NPY
      with norepinephrine, we investigated the involvement of NPY in long-term control
      of cardiovascular functions using NPY transgenic (NPY-tg) rats. These rats were
      developed by injection of the rat (Sprague-Dawley) pronuclei with a 14.5-kb clone
      of the rat structural NPY gene. When compared with nontransgenic littermates, NPY
      concentrations were significantly increased in a number of cardiovascular tissues
      of NPY-tg hemizygotes. Direct basal mean arterial pressure and heart rate were
      not changed, but calculated total vascular resistance was significantly increased
      in NPY-tg subjects. Arterial pressure increases, in response to norepinephrine
      injection, were greater in the NPY-tg rats. Also, the hypotension and bradycardia
      in response to hemorrhage were significantly reduced in NPY-tg subjects. These
      results indicate that NPY, when expressed in increased amounts, potentiates the
      pressor effects of norepinephrine and contributes to maintaining blood pressure
      during hemorrhage, but it does not alter resting blood pressure. These transgenic
      rats will facilitate studies of the role of NPY signaling in cardiovascular
      regulation, particularly regarding its functional cooperation with
      norepinephrine.

PMID- 11448844
TI  - Increased pyruvate flux capacities account for diet-induced increases in
      gluconeogenesis in vitro.
AB  - High-fat (HF) and high-sucrose (SU) diets increase gluconeogenesis. The present
      study was designed to determine the contributions of pyruvate dehydrogenase,
      pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate
      kinase fluxes to this accelerated gluconeogenesis (GNEO) in the absence and
      presence of fatty acids. Male Sprague-Dawley rats were fed an HF, SU, or starch
      (ST) diet for 1 wk, and hepatocytes or mitochondria were isolated. In the absence
      of palmitate, the tracer estimated rates of GNEO (nmol. min(-1). mg(-1)) were
      elevated in hepatocytes isolated from SU (32.3 +/- 1.8) and HF (35.4 +/- 1.8) vs.
      ST (22.8 +/- 1.5). Pyruvate carboxylase and PEPCK flux rates (nmol. min(-1). mg(
      1)) were increased in the SU (47.5 +/- 2.2 and 34.8 +/- 1.5) and HF (49.4 +/- 1.8
      and 38.2 +/- 1.8) groups compared with the ST group (32.8 +/- 3.2 and 44.3 +/-
      2.0). Palmitate (250-1,000 microM) stimulation of these fluxes was not
      significantly different among groups. Bromopalmitate, an inhibitor of fat
      oxidation, abolished differences in GNEO, pyruvate carboxylase, and PEPCK fluxes
      in HF and SU vs. ST. In isolated mitochondria, pyruvate carboxylation and
      palmitoyl carnitine oxidation were not significantly different among groups. The
      results of this study suggest that the increased gluconeogenic flux observed with
      HF and SU diets is associated with an increased pyruvate flux through pyruvate
      carboxylase and PEPCK. Moreover, the ability of bromopalmitate to normalize
      gluconeogenic fluxes suggests that endogenous fatty acids contribute to diet
      induced increases in GNEO.

PMID- 11448845
TI  - Sustained influence of the renal nerves to attenuate sodium retention in
      angiotensin hypertension.
AB  - Recent studies indicate that baroreflex suppression of renal sympathetic nerve
      activity is sustained for up to 5 days of ANG II infusion; however, steady-state
      conditions are not associated with ANG II hypertension of this short duration.
      Thus the major goal of this study was to determine whether neurally induced
      increments in renal excretory function during chronic intravenous infusion of ANG
      II are sustained under more chronic conditions when hypertension is stable and
      sodium balance is achieved. Experiments were conducted in five conscious dogs
      subjected to unilateral renal denervation and surgical division of the urinary
      bladder into hemibladders to allow separate 24-h urine collection from denervated
      (Den) and innervated (Inn) kidneys. ANG II was infused after control measurements
      for 10 days at a rate of 5 ng. kg(-1). min(-1). Twenty-four-hour control values
      for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from
      Den and Inn kidneys (Den/Inn) were 92 +/- 4 mmHg and 0.99 +/- 0.05, respectively.
      On days 8-10 of ANG II infusion, MAP was stable (+30 +/- 3 mmHg) and sodium
      balance was achieved. Whereas equal amounts of sodium were excreted from the
      kidneys during the control period, throughout ANG II infusion there was a greater
      rate of sodium excretion from Inn vs. Den kidneys (day 10 Den/Inn sodium = 0.56
      +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity.
      The greater rate of sodium excretion in Inn vs. Den kidneys during renal
      sympathoinhibition also revealed a latent impairment in sodium excretion from Den
      kidneys. Although the Den/Inn for sodium and the major metabolites of nitric
      oxide (NO) decreased in parallel during ANG II hypertension, the Den/Inn for
      cGMP, a second messenger of NO, remained at control levels throughout this study.
      This disparity fails to support the notion that a deficiency in NO production and
      action in Den kidneys accounts for the impaired sodium excretion. Most
      importantly, these results support the contention that baroreflex suppression of
      renal sympathetic nerve activity is sustained during chronic ANG II hypertension,
      a response that may play an important role in attenuating the rise in arterial
      pressure.

PMID- 11448846
TI  - Central melanocortin system modulates energy intake and expenditure of obese and
      lean Zucker rats.
AB  - Melanocortins play a critical role in appetite and body weight regulation,
      because manipulations of this pathway can lead to the development of obesity in
      several animal models. The purpose of this study was to use a melanocortin
      receptor agonist and antagonist to evaluate the involvement of melanocortins in
      feeding, energy metabolism, and body weight regulation in lean and obese Zucker
      rats. Central administration of a melanocortin receptor antagonist (SHU9119)
      elevated food intake and body weight of lean Zucker rats but had little effect in
      obese Zucker rats. In contrast, the melanocortin receptor agonist MTII reduced
      food intake in both lean and obese rats but was more potent in the obese Zucker
      rats. These data indicate the existence of functional melanocortin receptors in
      both lean and obese Zucker rats but suggest that obese Zucker rats have reduced
      endogenous melanocortin tone. In addition to its effects on food intake, MTII
      infusion elevated oxygen consumption and decreased respiratory quotient dose
      dependently during the light cycle. Our data suggest that a melanocortin receptor
      agonist can induce weight loss by increasing energy expenditure and promoting
      body fat utilization in addition to its inhibitory effects on food intake in both
      obese and lean Zucker rats.

PMID- 11448847
TI  - Role of metabotropic glutamate receptors in vasopressin and oxytocin release.
AB  - The effect of metabotropic glutamate receptor (mGluR) activation on vasopressin
      (VP) and oxytocin (OT) release was evaluated using explants of the
      hypothalamoneurohypophysial system. (+/-)-1-Aminocyclopentane-trans-1,3
      dicarboxylic acid (t-ACPD), an agonist at groups I and II mGluRs, increased VP
      and OT release in a concentration-dependent manner. A role for group I mGluRs in
      VP and OT release was demonstrated by the ability of a group I-specific mGluR
      antagonist, 1-aminoindan-1,5-idicarboxylic acid (AIDA), to block the effect of t
      ACPD and the ability of a group I-specific agonist, (R,S)-3,5
      dihydroxyphenylglycine, to significantly increase both VP (P = 0.0029) and OT (P
      = 0.0032) release. However, AIDA did not alter VP or OT release induced by a ramp
      increase in osmolality of the perifusion medium. The role of group III mGluRs was
      examined using L(+)-2-amino-4-phosphonobutyric acid (L-AP4), an agonist of these
      receptors. L-AP4 did not change basal release of VP or OT and did not prevent
      osmotically stimulated hormone release. Thus mGluR activation stimulates VP and
      OT release, but it is not required for osmotic stimulation of hormone release.

PMID- 11448848
TI  - Neuroendocrine and renal effects of intravascular volume expansion in compensated
      heart failure.
AB  - To examine if the neuroendocrine link between volume sensing and renal function
      is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/-
      0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood
      volume expansion by 3 h of water immersion (WI) elicits a natriuresis. In HF, WI
      suppressed ANG II and aldosterone (Aldo) concentrations, increased the release of
      atrial natriuretic peptide (ANP), and elicited a natriuresis (P < 0.05 for all)
      compared with seated control. Compared with control subjects (n = 9), ANG II,
      Aldo, and ANP concentrations were increased (P < 0.05) in HF, whereas absolute
      and fractional sodium excretion rates were attenuated [47 +/- 16 vs. 88 +/- 15
      micromol/min and 0.42 +/- 0.18 vs. 0.68 +/- 0.12% (mean +/- SE), respectively,
      both P < 0.05]. When ANG II and Aldo concentrations were further suppressed (P <
      0.05) during WI in HF (by sustained angiotensin-converting enzyme inhibitor
      therapy, n = 9) absolute and fractional sodium excretion increased (P < 0.05) to
      the level of control subjects (108 +/- 34 micromol/min and 0.70 +/- 0.23%,
      respectively). Renal free water clearance increased during WI in control subjects
      but not in HF, albeit plasma vasopressin concentrations were similar in the two
      groups. In conclusion, the neuroendocrine link between volume sensing and renal
      sodium excretion is preserved in compensated HF. The natriuresis of WI is,
      however, modulated by the prevailing ANG II and Aldo concentrations. In contrast,
      renal free water clearance is attenuated in response to volume expansion in
      compensated HF despite normalized plasma AVP concentrations.

PMID- 11448849
TI  - Differential sympathetic nerve and heart rate spectral effects of nonhypotensive
      lower body negative pressure.
AB  - Lower body negative pressure (LBNP; -5 and -15 mmHg) was applied to 14 men (mean
      age 44 yr) to test the hypothesis that reductions in preload without effect on
      stroke volume or blood pressure increase selectively muscle sympathetic nerve
      activity (MSNA), but not the ratio of low- to high-frequency harmonic component
      of spectral power (P(L)/P(H)), a coarse-graining power spectral estimate of
      sympathetic heart rate (HR) modulation. LBNP at -5 mmHg lowered central venous
      pressure and had no effect on stroke volume (Doppler) or systolic blood pressure
      but reduced vagal HR modulation. This latter finding, a manifestation of arterial
      baroreceptor unloading, refutes the concept that low levels of LBNP interrogate,
      selectively, cardiopulmonary reflexes. MSNA increased, whereas P(L)/P(H) and HR
      were unchanged. This discordance is consistent with selectivity of efferent
      sympathetic responses to nonhypotensive LBNP and with unloading of tonically
      active sympathoexcitatory atrial reflexes in some subjects. Hypotensive LBNP (-15
      mmHg) increased MSNA and P(L)/P(H), but there was no correlation between these
      changes within subjects. Therefore, HR variability has limited utility as an
      estimate of the magnitude of orthostatic changes in sympathetic discharge to
      muscle.

PMID- 11448850
TI  - Endothelin-1-induced vasoconstriction is inhibited during erection in rats.
AB  - Recent evidence indicates that endothelin-1 (ET-1) might be a principal
      vasoconstrictor in the penis. We report that ET-1 injection into the cavernous
      sinuses before erection sharply reduced the magnitude of subsequent erections.
      Corpus cavernosum pressure-to-mean arterial pressure ratios (CCP/MAP), with
      maximal ganglionic stimulation, were 0.62 +/- 0.05 before ET-1 injection and 0.31
      +/- 0.05 after, indicating that ET-1 acted as a vasoconstrictor. When ET-1 was
      injected during a maximal neurally induced erection, the ability of ET-1 to
      attenuate subsequent erections was diminished (CCP/MAP 0.75 +/- 0.02 before ET-1,
      0.61 +/- 0.03 after). At submaximal stimulation voltages, injection of ET-1
      during erection also attenuated its vasoconstrictive effect. Similarly, when ET-1
      was injected during erection induced by intracavernosal injection of the nitric
      oxide (NO) donor NOR-1, subsequent erections were not significantly suppressed
      (CCP/MAP 0.53 +/- 0.04 before ET-1, 0.45 +/- 0.04 after). These findings that ET
      1-induced vasoconstriction is attenuated during erection are consistent with the
      hypothesis that NO mediates erection both by initiating pathways that cause
      smooth muscle relaxation and by inhibiting the vasoconstrictive actions of ET-1.

PMID- 11448851
TI  - Voluntary physical activity prevents stress-induced behavioral depression and
      anti-KLH antibody suppression.
AB  - The current study addressed whether physical activity can buffer stress-induced
      "behavioral depression" and immunosuppression. Adult, male Sprague-Dawley rats
      were housed with either a mobile (physically active) or immobile (sedentary)
      running wheel and exposed to either stress (inescapable tail shock) or no stress
      (home cage control). Voluntary wheel running began 4 wk before stressor exposure.
      Immediately before stress, all rats were administered an intraperitoneal
      injection of keyhole limpet hemocyanin (KLH; 200 microg), and anti-KLH Ig was
      measured weekly for 4 wk using ELISA. Prior physical activity reduced the stress
      induced behavioral depression and prevented the stress-induced suppression of
      anti-KLH IgM and IgG(2a) antibodies. Anti-KLH IgG(1) was stress insensitive.
      These data suggest that physical activity can buffer the negative impact of
      stress on behavior and acquired immune function.

PMID- 11448852
TI  - Unsteady-state gas exchange and storage in diving marine mammals: the harbor
      porpoise and gray seal.
AB  - Breath-by-breath measurements of end-tidal O(2) and CO(2) concentrations in
      harbor porpoise reveal that the respiratory gas exchange ratio (R(R); CO(2)
      output/O(2) uptake) of the first lung ventilation in a breathing bout after a
      prolonged breath-hold is always well below the animal's metabolic respiratory
      quotient (RQ) of 0.85. Thus the longest apneic pauses are always followed by an
      initial breath having a very low R(R) (0.6-0.7), which thereafter increases with
      each subsequent breath to values in excess of 1.2. Although the O(2) stores of
      the body are fully readjusted after the first three to four breaths following a
      prolonged apneic pause, a further three to four ventilations are always needed,
      not to load more O(2) but to eliminate built-up levels of CO(2). The slower
      readjustment of CO(2) stores relates to their greater magnitude and to the fact
      that they must be mobilized from comparatively large and chemically complex
      HCO/CO(2) stores that are built up in the blood and tissues during the breath
      hold. These data, and similar measurements on gray seals (12), indicate that it
      is the readjustment of metabolic RQ and not O(2) stores per se that governs the
      amount of time an animal must spend ventilating at the surface after a dive.

PMID- 11448853
TI  - Role of calcium channels and adenylate cyclase in the PACAP-induced adrenal
      catecholamine secretion.
AB  - We elucidated the functional contribution of voltage-dependent calcium channels
      (VDCCs) and adenylate cyclase to epinephrine (Epi) and norepinephrine (NE)
      secretion induced by pituitary adenylate cyclase-activating polypeptide (PACAP)
      in the isolated perfused rat adrenal gland. PACAP increased Epi and NE output,
      which was inhibited by perfusion with calcium-free solution or by nifedipine, an
      L-type VDCC blocker. However, the PACAP-induced responses were resistant to omega
      conotoxin GVIA, an N-type VDCC blocker, or omega-conotoxin MVIIC, a P/Q-type VDCC
      blocker. MDL-12330A, an adenylate cyclase inhibitor, inhibited the PACAP-induced
      increase in Epi, but not NE, output. Treatment with nifedipine and MDL-12330A
      caused additive inhibition of the PACAP-induced catecholamine responses. These
      results suggest that opening of L-type VDCCs is responsible for adrenal
      catecholamine secretion induced by PACAP and that activation of adenylate cyclase
      is involved in the PACAP-induced Epi, but not NE, secretion. These pathways may
      act independently of each other.

PMID- 11448854
TI  - Parasite infection and caloric restriction induce physiological and morphological
      plasticity.
AB  - To investigate the effects of parasitism and caloric restriction on morphology
      (body composition, organ mass) and physiology (resting metabolism, intestinal
      glucose transport capacity), we gave laboratory mice intestinal parasites
      (Heligmosomoides polygyrus, Nematoda), 30% caloric restriction, or both.
      Calorically restricted mice had smaller body mass, enhanced glucose transport
      capacity, and lower resting metabolism than ad libitum-fed mice. Parasitized mice
      maintained body mass, had diminished intestinal glucose transport capacity, and
      greater resting metabolism than unparasitized mice. Parasitized, calorically
      restricted mice had smaller organ masses than parasitized, ad libitum-fed mice
      and did not increase their glucose uptake rate as much as unparasitized,
      calorically restricted mice. There was a significant interaction between caloric
      restriction and parasite status for morphological variables but not for
      physiological variables. Knowing the types of phenotypic changes that occur with
      simultaneous parasitism and caloric restriction will provide insight into
      understanding human helminthiasis in food-restricted communities and also how
      wild animals cope with environments where parasitism and seasonal food
      restriction are common.

PMID- 11448855
TI  - Force reduction uncoupled from pH and H(2)PO(-)(4) in rat gastrocnemius in vivo
      with continuous 2-Hz stimulation.
AB  - The aim of this study was to examine the effect of the products of ATP hydrolysis
      on the fatigue process in rat gastrocnemius in vivo. Adult male Sprague-Dawley
      rats (300-400 g) were anesthetized and ventilated in a custom-built cradle fitted
      with a force transducer that could be placed into a 7-T NMR magnet. The muscle
      was stimulated continuously at 2 Hz for 20 min (n = 7). Isometric twitch force
      increased in the first 4 min of stimulation accompanied by changes in twitch
      duration (20% increase in relaxation time). Prolonged relaxation was associated
      with changes in cytosolic pH (6.91 to 6.58), lactate (1.8 to 12.6 micromol/g wet
      wt), and H(2)PO (7.57 to 13.99 mM). After 4 min, relaxation time, pH, lactate,
      and H(2)PO returned toward control values as twitch force progressively
      decreased. No correlation was found between force decline (or twitch broadening)
      and total phosphate (3 to 23 mM), free [ADP] (18 to 95 microM), free [Mg(2+)]
      (0.58 to 0.96 mM), or free energy of ATP hydrolysis (-65 to -55 kJ/mol). We
      conclude that force decline is not due to increased pH and/or H(2)PO but to
      fatigue of the fast-twitch fibers, possibly linked to glycogen depletion and/or
      failure of nerve impulse transmission in these fibers.

PMID- 11448856
TI  - Energy intake and fur in summer- and winter-acclimated Siberian hamsters
      (Phodopus sungorus).
AB  - Few studies have directly addressed the impact of fur on seasonal changes in
      energy intake. The daily food intake of Siberian hamsters (Phodopus sungorus) was
      measured under simulated summer and winter conditions in intact animals and those
      with varying amounts of pelage removed. Energy intake increased up to 44% above
      baseline control values for approximately 2-3 wk after complete shaving.
      Increases in food intake varied with condition and were greater in hamsters
      housed in short than long day lengths and at low (5 degrees C) than moderate (23
      degrees C) ambient temperatures. Removal of 8 cm(2) of dorsal fur, equivalent to
      30% of the total dorsal fur surface, increased food intake, but removal of 4
      cm(2) had no effect. An 8-cm(2) fur extirpation from the ventral surface did not
      increase food consumption. Food intake was not influenced differentially by fur
      removal from above brown adipose tissue hot spots. Fur plays a greater role in
      energy balance in winter- than summer-acclimated hamsters and conserves energy
      under a wide range of environmental conditions.

PMID- 11448857
TI  - Brain stem PO(2) and pH of the working heart-brain stem preparation during
      vascular perfusion with aqueous medium.
AB  - The rat working heart-brain stem preparation (WHBP) is an in situ preparation
      having many of the advantages associated with in vitro preparations while
      retaining cardiovascular response functionality and an eupnoeic respiratory motor
      pattern. The preparation is perfused arterially with an aqueous medium having a
      much lower oxygen-carrying capacity than blood. To evaluate the efficacy of the
      artificial perfusion in providing adequate gas exchange within the brain stem, we
      used polarographic PO(2) and pH microelectrodes to determine the tissue PO(2) and
      pH of the medulla oblongata at various depths. When the perfusate was
      equilibrated with 5% CO(2) and 95% O(2), average tissue PO(2) was 294 Torr and no
      hypoxic areas were encountered. Tissue pH was remarkably uniform throughout the
      tissue, and on average was only 0.04 +/- 0.02 pH units more acidic than that of
      the perfusate. Increasing the PCO(2) of the perfusate increased tissue PO(2) and
      decreased arterial resistance. Decreasing perfusate PCO(2) (while keeping pH
      constant) decreased tissue PO(2) and reduced the respiratory activity. These
      results suggest that arterial PCO(2), independent of arterial pH, is an essential
      variable in determining both respiratory drive and cerebrovascular perfusion. We
      conclude that the medulla of the WHBP is oxygenated and within a physiological
      pH, which accounts for the eupneic pattern of respiratory motor activity it
      generates. Furthermore, this preparation may be a useful model for exploring
      mechanisms of central chemoreception as well as the dynamics of the cerebral
      vasculature responses following changes in blood gases.

PMID- 11448858
TI  - Muscle angiogenic growth factor gene responses to exercise in chronic renal
      failure.
AB  - Patients with chronic renal failure (CRF) have impaired exercise capacity even
      after erythropoietin treatment. We recently showed that although this is
      explained in part by reduced convective O(2) delivery to muscles, there is also
      an impairment of O(2) transport from muscle capillaries to the mitochondria.
      Given the importance of the capillary surface area for capillary mitochondrial
      O(2) transport and reports of reduced capillarity in CRF, we hypothesized that
      the angiogenic gene response to exercise is impaired in such patients. Six
      patients with CRF and six control subjects matched for age, size, and sedentary
      lifestyle exercised on a single occasion for 1 h at similar work intensities
      averaging 50% of maximal capacity. Exercise was confined to the knee extensors of
      a single leg by means of a specially designed leg-kick ergometer. A percutaneous
      biopsy of the quadriceps was taken within 30 min of cessation of exercise and
      compared with a similar biopsy done at different times without any prior exercise
      for 24 h. Conventional Northern blots were prepared and probed for vascular
      endothelial growth factor (VEGF; the major putative angiogenic growth factor for
      muscle), basic fibroblast growth factor (bFGF), and transforming growth factor
      (TGF)-beta(1). Data during both rest and exercise were successfully obtained in
      four subjects of each group. We also assessed muscle capillarity and
      mitochondrial oxidative capacity to relate to these changes. Mitochondrial
      oxidative capacity was normal, whereas capillary number per fiber was 12% lower
      than in normal subjects. VEGF mRNA abundance was increased after exercise by
      about one order of magnitude, with no reduction in response in CRF. For bFGF and
      TGF-beta(1), exercise elicited no response in either group. Reduced muscle
      capillarity in CRF does not, therefore, stem from reduced transcription of VEGF.
      To the extent that VEGF is important to exercise-induced angiogenesis in muscle,
      we suspect a posttranscriptional aberration in this response occurs in CRF to
      explain reduced capillarity.

PMID- 11448859
TI  - Cardiovascular and renal responses to a high-fat diet in Osborne-Mendel rats.
AB  - This study examined the cardiovascular, renal, and hormonal responses of dietary
      induced obesity in Osborne-Mendel (OM) rats. Male OM rats were fed either a low
      (LF; n = 10)- or high-fat (HF; n = 11) diet for 17 wk. During week 15 of the
      study, arterial pressure was measured directly, 24 h/day, from chronically
      indwelling catheters. Body and kidney weights were 46 +/- 5 and 33 +/- 5%
      greater, respectively, in rats fed HF vs. LF diet. Left and right ventricular
      weights were also greater in rats fed HF diet (21 +/- 7 and 36 +/- 6%,
      respectively). Direct measurement of arterial pressure revealed only a slight
      increase in mean arterial pressure (88 +/- 1 in rats fed HF diet vs. 85 +/- 1
      mmHg in rats fed LF diet), whereas there was no difference in resting heart rate
      between the two groups. Consumption of HF diet was also associated with a 3.5
      fold increase in plasma insulin, a 16 +/- 4% higher blood glucose, and a 40 +/-
      6% reduction in plasma renin activity compared with LF-fed rats. Thus feeding OM
      rats HF diet led to obesity, cardiac and renal hypertrophy, and hyperinsulinemia
      but only a slight increase in mean arterial pressure.

PMID- 11448860
TI  - Dietary soy exerts an antihypertensive effect in spontaneously hypertensive
      female rats.
AB  - This study tested the hypothesis that dietary soy would attenuate the development
      of hypertension in female spontaneously hypertensive rats (SHR). Female SHR and
      control Wistar-Kyoto rats were obtained at 4 wk of age, randomly assigned to
      either an ovariectomized (OVX) group or a sham-operated group, and placed on a
      soy diet or control casein diet. After a minimum of 8 wk on their respective
      diets, mean arterial pressure (MAP) and heart rate (HR) were recorded before and
      after inhibition of nitric oxide synthase, air-jet stress, or ganglionic
      blockade. The major finding of this study is that MAP was reduced in the OVX SHR
      consuming soy diet compared with the casein-fed controls (150 +/- 4 vs. 164 +/- 3
      mmHg). Plasma genistein concentrations were increased in the soy-fed OVX SHR
      (1.23 +/- 0.31 microM) compared with the casein-fed OVX SHR (nondetectable).
      However, there was no difference in plasma genistein concentrations between sham
      operated and OVX SHR (1.37 +/- 0.42 vs. 1.23 +/- 0.31 microM). Inhibition of
      nitric oxide synthase increased MAP and decreased HR in all groups; diet did not
      affect this response. Air-jet stress increased MAP and HR in all groups. However,
      these responses were exaggerated in the soy-fed SHR. Finally, ganglionic blockade
      abolished the antihypertensive effect of soy diet in the OVX SHR. These findings
      indicate that dietary soy exerts an antihypertensive effect in OVX SHR. This
      effect does not involve the nitric oxide system but may be related to an as yet
      undefined interaction with the autonomic nervous system.

PMID- 11448861
TI  - Insulin-independent, MAPK-dependent stimulation of NKCC activity in skeletal
      muscle.
AB  - Na(+)-K(+)-Cl(-) cotransporter (NKCC) activity in quiescent skeletal muscle is
      modest. However, ex vivo stimulation of muscle for as little as 18 contractions
      (1 min, 0.3 Hz) dramatically increased the activity of the cotransporter,
      measured as the bumetanide-sensitive (86)Rb influx, in both soleus and plantaris
      muscles. This activation of cotransporter activity remained relatively constant
      for up to 10-Hz stimulation for 1 min, falling off at higher frequencies (30-Hz
      stimulation for 1 min). Similarly, stimulation of skeletal muscle with adrenergic
      receptor agonists phenylephrine, isoproterenol, or epinephrine produced a
      dramatic stimulation of NKCC activity. It did not appear that stimulation of NKCC
      activity was a reflection of increased Na(+)-K(+)-ATPase activity because insulin
      treatment did not stimulate NKCC activity, despite insulin's well-known
      stimulation of Na(+)-K(+)-ATPase activity. Stimulation of NKCC activity could be
      blocked by pretreatment with inhibitors of mitogen-activated protein kinase
      (MAPK) kinase 1/2 (MEK1/2) activity, indicating that activation of the
      extracellular signal-regulated kinase 1/2 (ERK1/2) MAPKs may be required. These
      data indicate a regulated NKCC activity in skeletal muscle that may provide a
      significant pathway for potassium transport into skeletal muscle fibers.

PMID- 11448862
TI  - Ascorbate dynamics and oxygen consumption during arousal from hibernation in
      Arctic ground squirrels.
AB  - During hibernation in Arctic ground squirrels (Spermophilus parryii), O(2)
      consumption and plasma leukocyte counts decrease by >90%, whereas plasma
      concentrations of the antioxidant ascorbate increase fourfold. During rewarming,
      O(2) consumption increases profoundly and plasma ascorbate and leukocyte counts
      return to normal. Here we investigated the dynamic interrelationships among these
      changes. Plasma ascorbate and uric acid (urate) concentrations were determined by
      HPLC from blood samples collected at approximately 15-min intervals via arterial
      catheter; leukocyte count and hematocrit were also determined. Body temperature,
      O(2) consumption, and electromyographic activity were recorded continuously.
      Ascorbate, urate, and glutathione contents in body and brain samples were
      determined during hibernation and after arousal. During rewarming, the maximum
      rate of plasma ascorbate decrease occurred at the time of peak O(2) consumption
      and peak plasma urate production. The ascorbate decrease did not correlate with
      mouth or abdominal temperature; uptake into leukocytes could account for only a
      small percentage. By contrast, liver and spleen ascorbate levels increased
      significantly after arousal, which could more than account for ascorbate
      clearance from plasma. Brain ascorbate levels remained constant. These data
      suggest that elevated concentrations of ascorbate [(Asc)] in plasma [(Asc)(p)]
      provide an antioxidant source that is redistributed to tissues during the
      metabolic stress that accompanies arousal.

PMID- 11448863
TI  - Renal effects of nitric oxide synthase inhibition in conscious water-loaded dogs.
AB  - The renal effects of the nitric oxide (NO) synthase inhibitor nitro-L-arginine
      methyl ester (L-NAME) were investigated in conscious dogs undergoing sustained
      water diuresis and replacement of urinary sodium losses. Experiments were
      performed with and without additional extracellular volume expansion (isotonic
      saline, 2% body wt). L-NAME (10 microg. kg(-1). min(-1)) infused during water
      diuresis decreased urine flow (2.5 +/- 0.2 to 1.5 +/- 0.3 ml/min), free water
      clearance (1.9 +/- 0.2 to 1.0 +/- 0.2 ml/min), and sodium excretion (4.0 +/- 1.7
      to 2.1 +/- 0.6 micromol/min). Arterial blood pressure increased from 112 +/- 2 to
      126 +/- 3 mmHg, but creatinine clearance did not measurably change. Plasma
      endothelin and vasopressin concentrations and plasma renin activity (PRA) were
      unchanged. Urinary endothelin concentration increased (3.4 +/- 0.8 to 6.2 +/- 1.7
      pg/ml), but the excretion rate remained constant. L-Arginine infusion (0.6 mg.
      kg(-1). min(-1)) along with L-NAME abolished the renal effects but not the blood
      pressure increase. Volume expansion increased urine flow (2.5 +/- 0.4 to 5.7 +/-
      0.5 ml/min) and sodium excretion (3.8 +/- 1.6 to 76.5 +/- 14.5 micromol/min). L
      NAME attenuated the renal effects of volume expansion: urine flow increased to
      2.8 +/- 0.7 ml/min and sodium excretion to 34 +/- 17 micromol/min. PRA decreased
      with control volume expansion but not during L-NAME. Urinary endothelin levels
      were elevated by L-NAME, decreased with volume expansion in all series, but
      excretion rate remained constant. Infusion of L-arginine partially reversed these
      effects of L-NAME. The results demonstrate that NO synthase inhibition increases
      blood pressure and blunts the renal responses to water and saline loading.

PMID- 11448864
TI  - Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during
      heat stress.
AB  - It is not clear whether the diurnal variation in the cutaneous circulatory
      response to heat stress is via the noradrenergic vasoconstrictor system or the
      nonadrenergic active vasodilator system. We conducted whole body heating
      experiments in eight male subjects at 0630 (AM) and 1630 (PM). Skin blood flow
      was monitored by laser-Doppler flowmetry at control sites and at sites pretreated
      with bretylium (BT) to block noradrenergic vasoconstriction. Noninvasive blood
      pressure was used to calculate cutaneous vascular conductance. The sublingual
      temperature (T(or)) threshold for cutaneous vasodilation was significantly higher
      in PM at control and at BT-treated sites (both P < 0.01), suggesting the diurnal
      shift in threshold depends on the active vasodilator system. The slope of
      cutaneous vascular conductance as a percentage of its maximum with respect to
      T(or) was significantly lower in AM at control sites only. Also, in the AM, the
      slope at control sites was significantly lower than that at BT-treated sites (P <
      0.05), suggesting that the diurnal change in the sensitivity of cutaneous
      vasodilation depends on vasoconstrictor system function. Overall, the diurnal
      variation in the reflex control of skin blood flow during heat stress involves
      both vasoconstrictor and active vasodilator systems.

PMID- 11448865
TI  - Increased flavor preference and lick activity for sucrose and corn oil in SWR/J
      vs. AKR/J mice.
AB  - Nutrient preferences and orosensory responses were characterized in two mouse
      inbred strains. In two-bottle solution tests (tastant vs. vehicle; ascending
      concentrations), the effects of strain and chow type (12 or 26% fat) on
      preference thresholds for sucrose and corn oil were compared in AKR/J and SWR/J
      mice. SWR/J mice displayed lower preference thresholds and ingested more sucrose
      than AKR/J mice did. SWR/J mice also showed lower preference thresholds and
      consumed more corn oil than AKR/J mice did; corn oil preference was suppressed
      3.5-fold in AKR/J mice compared with SWR/J mice when fed 26% fat chow. Next,
      licking was recorded during 30-s access to sucrose or corn oil across a range of
      concentrations. SWR/J mice licked the tastants more than AKR/J mice did. Analysis
      of modal interlick intervals during lick training revealed that SWR/J mice licked
      water faster than AKR/J mice when water deprived, suggesting that motor as well
      as sensory factors may determine lick responses to tastants in brief-access
      tests. Finally, in two-bottle tests pitting maximally preferred concentrations of
      sucrose (8 or 16%) against corn oil (20%), SWR/J mice highly preferred sucrose
      over corn oil at either sucrose concentration. AKR/J mice preferred corn oil over
      8% sucrose but reversed their preference when 16% sucrose was offered. These
      results support a primary role of flavor in the nutrient preferences of SWR/J
      mice. In AKR/J mice, the low lick activity for sucrose and corn oil and greater
      suppression of corn oil preference by the high-fat chow suggest that their
      preferences depend more on postingestive factors than on flavor.

PMID- 11448866
TI  - Effects of catecholamines on the pulmonary circulation in the ovine fetus.
AB  - High levels of circulating catecholamines are found in the fetus, and fetal
      stress and birth induce a marked surge in catecholamine secretion. Little is
      known about the role of catecholamines on the fetal pulmonary circulation. To
      determine the effects of catecholamines on the pulmonary vascular tone, we tested
      the hemodynamic response to norepinephrine and dopamine infusion in chronically
      prepared late-gestation fetal lambs. We found that norepinephrine infusion (0.5
      microg. kg(-1). min(-1)) increased pulmonary artery pressure (PAP) by 10 +/- 1%
      (P < 0.01), left pulmonary artery blood flow by 73 +/- 14% (P < 0.01), and
      decreased pulmonary vascular resistance (PVR) by 33 +/- 6% (P < 0.01). The
      pulmonary vasodilator effect of norepinephrine was abolished after nitric oxide
      synthase inhibition. Dopamine infusion at 5 microg. kg(-1). min(-1) did not
      significantly change PVR. Conversely, dopamine infusion at 10 microg. kg(-1).
      min(-1) increased PAP (P < 0.01) and progressively increased PVR by 30 +/- 14% (P
      < 0.01). These results indicate that catecholamines may modulate basal pulmonary
      vascular tone in the ovine fetus. We speculate that catecholamines may play a
      significant role in the maintenance of the fetal pulmonary circulation and in
      mediating changes in the transitional pulmonary circulation.

PMID- 11448867
TI  - Differential role of adrenoceptors in control of plasma glucose and fatty acids
      in carp, Cyprinus carpio (L.).
AB  - Carp were cannulated in the dorsal aorta, and after 2 days of recovery they were
      infused with 1) norepinephrine, 2) yohimbine (alpha(2)-antagonist) plus
      norepinephrine, 3) clonidine (alpha(2)-agonist), and 4) isoproterenol
      (nonselective beta-agonist). Norepinephrine lowered the plasma free fatty acid
      (FFA) level and raised the plasma glucose level for several hours. Norepinephrine
      in combination with the alpha(2)-antagonist yohimbine resulted in retardation of
      the FFA decrease, indicating the involvement of alpha(2)-adrenoceptors. Infusion
      with the partial alpha(2)-agonist clonidine had a smaller effect. Infusion with
      isoproterenol caused a marked increase of glucose levels, and unexpectedly a
      decline of plasma FFA levels, indicating a direct involvement of beta
      adrenoceptors. Combination of isoproterenol with either atenolol (beta(1)
      antagonist) or ICI-118,551 (beta(2)-antagonist) showed that both beta(1)- and
      beta(2)-adrenoceptors were involved in the glucose release by isoproterenol.
      Remarkably, the decline of FFA levels was augmented in the presence of ICI
      118,551, whereas with atenolol present plasma FFA levels were increased by
      isoproterenol. Thus it is concluded that in carp both beta(1)- and beta(2)
      adrenoceptors mediate glucose release, whereas lipolysis is controlled by
      inhibitory beta(1)-adrenoceptors and stimulatory beta(2)-adrenoceptors, as well
      as by inhibitory alpha(2)-adrenoceptors.

PMID- 11448868
TI  - Muscle sympathetic outflow during horizontal linear acceleration in humans.
AB  - To elucidate the effects of linear acceleration on muscle sympathetic nerve
      activity (MSNA) in humans, 16 healthy men were tested in a linear accelerator.
      Measurements of MSNA, electrocardiogram, blood pressure, and thoracic impedance
      were undertaken during linear acceleration. Sinusoidal linear acceleration with
      peak values at +/-0.10, +/-0.15, and +/-0.20 G was applied in anteroposterior (+/
      G(x), n = 10) or lateral (+/-G(y), n = 6) directions. The total activity and
      burst rate of MSNA decreased significantly during forward, backward, left, or
      right linear accelerations. The total activity of MSNA decreased to 50.5 +/- 6.9,
      52.5 +/- 4.4, 71.2 +/- 9.6, and 67.6 +/- 8.2% from the baselines (100%) during
      linear accelerations with peak values at +/-0.20 G in the four directions,
      respectively. These results suggest that dynamic stimulation of otolith organs in
      horizontal directions in humans might inhibit MSNA directly in order to quickly
      redistribute blood to muscles during postural reflexes induced by passive
      movement, which supports the concept that the vestibular system contributes to
      sympathetic regulation in humans.

PMID- 11448869
TI  - Synaptic plasticity in sympathetic ganglia from acquired and inherited forms of
      ouabain-dependent hypertension.
AB  - Altered sympathetic nervous system activity has been implicated often in
      hypertension. We examined short-term potentiation [posttetanic potentiation
      (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia
      (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by
      subcutaneous implants as well as in animals with ouabain-induced hypertension
      (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain
      sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP)
      were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s).
      Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD
      rats before tetanus, but the decay time constant of PTP was significantly
      decreased in OHR and in rats infused with digoxin that were normotensive. In
      hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP
      (t(L)) were increased and correlated with blood pressure (slope = 0.15 min/mmHg,
      r = 0.52, P < 0.047 and 6.7 min/mmHg, r = 0.906, P < 0.0001, respectively). In
      BOS and OHR, t(L) (minutes) was 492 +/- 40 (n = 7) and 539 +/- 41 (n = 5),
      respectively, and differed (P < 0.05) from BOR (257 +/- 48, n = 4), SD vehicle
      rats (240 +/- 18, n = 4), and captopril-treated OHR (370 +/- 52, n = 5). After
      the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD
      vehicle rats or BOR. Captopril normalized blood pressure and t(L) in OHR. We
      conclude that the duration of ganglionic LTP and blood pressure are tightly
      linked in ouabain-dependent hypertension. Our results favor the possibility that
      enhanced duration of LTP in sympathetic neurons contributes to the increase in
      sympathetic nerve activity in ouabain-dependent hypertension and suggest that a
      captopril-sensitive step mediates the link of ouabain with LTP.

PMID- 11448870
TI  - PYY inhibits CCK-stimulated pancreatic secretion through the area postrema in
      unanesthetized rats.
AB  - Peptide YY (PYY) inhibits CCK-8-secretin-stimulated pancreatic secretion in vivo.
      To investigate whether CCK-8-secretin-stimulated pancreatic secretion is mediated
      through a vago-vagal pathway and whether PYY inhibits this pathway through the
      area postrema (AP), chronic pancreatic, biliary, and duodenal catheters were
      implanted in AP-lesioned (APX) or sham-operated rats. The effects of APX on
      pancreatic secretion stimulated by bethanechol, pancreatic juice diversion (PJD),
      or CCK-8-secretin, were tested, with and without background PYY infusion, in
      unanesthetized rats. APX reduced basal pancreatic secretion by 15-20% (P < 0.01).
      APX had no effect on bethanechol-stimulated secretion and potentiated protein
      secretion stimulated by PJD (396 vs. 284%) and exogenous CCK-8-secretin. In sham
      operated rats, background PYY potently inhibited CCK-8-secretin-stimulated
      pancreatic fluid (1.8 vs. 48.2%) and protein secretion (3.7 vs. 45.8%) but
      potentiated fluid (52.9 vs. 43.1%) and protein (132.9 vs. 68.9%) secretion in APX
      rats. Our findings demonstrate that PYY inhibits CCK-8-secretin-stimulated
      pancreatic secretion through an AP-dependent mechanism in sham-operated rats. The
      AP also contributes to basal pancreatic secretion.

PMID- 11448871
TI  - The small intestine is an important source of adrenomedullin release during
      polymicrobial sepsis.
AB  - Adrenomedullin (AM), a potent vasodilatory peptide, has recently been reported to
      be involved in the altered cardiovascular responses under various
      pathophysiological conditions. Although the increase in plasma AM levels is
      associated with upregulation of AM gene expression in various tissues, it remains
      unknown whether the gut is an important source of AM release under such
      conditions. To determine this, adult male rats were subjected to sepsis by cecal
      ligation and puncture (CLP) followed by fluid resuscitation. Systemic and portal
      blood samples were collected simultaneously at 10 and 20 h after CLP or sham
      operation. A portion of the jejunum was also harvested. Plasma and tissue levels
      of AM were then determined by RIA. The localization of AM in the intestinal
      tissue was examined using immunohistochemistry. In an additional group of normal
      rats, synthetic rat AM (8.5 microg/kg body wt) was infused for 15 min at a
      constant rate via the portal vein (which produces a similar level of AM as
      observed during sepsis). Cardiac output, stroke volume, total peripheral
      resistance, and microvascular blood flow in various organs were determined before
      and 30 min after AM administration. The results indicate that AM levels in portal
      blood were significantly higher than in systemic blood at 10 and 20 h after CLP.
      Intestinal AM was also markedly elevated. Immunohistochemical visualization shows
      that AM immunostainings were localized in the mucosa, submucosa, and intestinal
      nerve fibers, and they were increased at 10-20 h post-CLP. Because AM
      immunopositive nerve fibers increase in the gut during sepsis, a nerve pathway
      may be involved in the regulation of vascular reactivity by this peptide.
      Moreover, intraportal administration of AM increased cardiac output, stroke
      volume, and microvascular blood flow in the liver, kidney, small intestine, and
      spleen. In contrast, total peripheral resistance was significantly reduced. Thus
      the gut plays an important role in increasing the levels of circulating AM during
      the progression of sepsis. Gut-derived AM appears to be a major factor in
      initiating the hyperdynamic response after the onset of sepsis.

PMID- 11448872
TI  - Transplantation of metanephroi after preservation in vitro.
AB  - To determine whether transplanted metanephroi grow, differentiate, and function
      in hosts after preservation in vitro, we implanted metanephroi from embryonic day
      15 (E15) Sprague-Dawley rat embryos into the omentum of nonimmunosuppressed
      uninephrectomized Sprague-Dawley (host) rats. Metanephroi were either implanted
      directly or suspended in ice-cold University of Wisconsin (UW) preservation
      solution with or without added growth factors for 3 days before implantation. The
      size and extent of tissue differentiation preimplantation of E15 metanephroi
      implanted directly were not distinguishable from the size and differentiation of
      metanephroi preserved for 3 days. In contrast, E16 metanephroi were larger than
      E15 metanephroi preserved for 3 days. E16 metanephroi or E13 metanephroi grown in
      organ culture for 3 days contained more differentiated nephron structures than
      those in E15 metanephroi preserved for 3 days. By 4 wk posttransplantation,
      metanephroi that had been preserved for 3 days had grown and differentiated such
      that glomeruli, proximal and distal tubules, and collecting ducts with normal
      structure had developed. At 12 wk posttransplantation, inulin clearances of
      preserved metanephroi were comparable to those of metanephroi that had been
      implanted directly. Addition of growth factors to the UW solution enhanced inulin
      clearances. Here we show for the first time that functional kidneys develop from
      metanephroi transplanted from rat embryos to adult rats after as long as 3 days
      of preservation in vitro.

PMID- 11448873
TI  - CNS sympathetic outflow neurons to white fat that express MEL receptors may
      mediate seasonal adiposity.
AB  - Many animals show seasonal changes in adiposity that are triggered by changes in
      the photoperiod. For example, in short "winterlike" days, the nocturnal duration
      of pineal melatonin (MEL) secretion increases ultimately resulting in body fat
      decreases by Siberian hamsters. These decreases in body fat are mediated through
      increases in the sympathetic drive on white adipose tissue (WAT). The central
      nervous system (CNS) origins of the sympathetic outflow from brain to WAT include
      the suprachiasmatic nucleus (SCN), an area necessary for the reception of season
      encoded MEL signals in Siberian hamsters. Therefore, we tested whether SCN
      neurons that are part of the sympathetic outflow to WAT also express MEL
      receptors (MEL(1a)). This was accomplished by labeling the sympathetic outflow
      from brain to WAT using a transsynaptic retrograde tract tracer, the pseudorabies
      virus (PRV), injected into inguinal WAT combined with labeling of brain MEL(1a)
      receptors using in situ hybridization. We found PRV-labeled neurons that also
      expressed MEL(1a)-receptor mRNA in several brain regions including the SCN. Thus
      the increased duration of MEL secretion in short days may increase MEL(1a)
      receptor stimulation that, in turn, increases the sympathetic drive on WAT,
      thereby increasing lipolysis and decreasing adiposity.

PMID- 11448874
TI  - Role of alpha-MSH in the regulation of consummatory behavior: immunohistochemical
      evidence.
AB  - Central injection of alpha-melanocyte-stimulating hormone (alpha-MSH) decreases
      food intake, suggesting a role for this peptide in the mediation of satiety.
      Inasmuch as alpha-MSH also supports the development of taste aversions under
      certain conditions, the nature of its influence on ingestive behavior, i.e.,
      whether it is related to satiety or aversion, remains unclear. In the present
      studies, we used immunostaining, including that for c-Fos as a marker of neuronal
      activation, to further substantiate the physiological role for alpha-MSH in the
      regulation of consummatory behavior. We found that an increase in activation of
      alpha-MSH neurons in the arcuate nucleus coincided with meal termination.
      Administration of powerful aversive agents, LiCl and CuSO(4), did not stimulate
      alpha-MSH cells but did induce pronounced activation of oxytocin (OT) and
      vasopressin (VP) neurons, the final components of circuitry mediating aversion.
      We observed fewer Fos-positive OT/VP neurons after alpha-MSH injection into the
      lateral ventricle or into the hypothalamic paraventricular nucleus, treatments
      that cause mild or no aversion, respectively. The degree of activation of OT/VP
      neurons paralleled the magnitude of aversive response to a given treatment. Our
      data support the hypothesis that, in the arcuate nucleus, alpha-MSH acts as a
      satiety mediator independent from aversion-related mechanisms.

PMID- 11448875
TI  - Reading the book of life.

PMID- 11448876
TI  - LDB2000: sequence-based integrated maps of the human genome.
AB  - MOTIVATION: Integrated maps are useful for gene mapping and establishing the
      relationship between recombination and sequence. In this paper we describe
      algorithms and their implementation for constructing sequence-based integrated
      maps of the human chromosomes, which are presented in LDB2000, a web based
      resource. Gene mapping efforts are now focussing on linkage disequilibrium
      mapping and extension of the integrated map to represent the extent of linkage
      disequilibrium in different genomic regions would further increase the utility of
      these maps. RESULTS: Sequence-based integrated maps have been completed for
      chromosomes 21 and 22. These maps provide locations for genes and polymorphic
      markers in sequence and on genetic linkage, radiation hybrid and cytogenetic
      scales. Single nucleotide polymorphisms associated with genes in the maps are
      also included and their sequence locations indicated. Related locus information,
      such as aliases and expression information, can be searched on the WWW site.

PMID- 11448877
TI  - Extending traditional query-based integration approaches for functional
      characterization of post-genomic data.
AB  - MOTIVATION: To identify and characterize regions of functional interest in
      genomic sequence requires full, flexible query access to an integrated, up-to
      date view of all related information, irrespective of where it is stored (within
      an organization or across the Internet) and its format (traditional database,
      flat file, web site, results of runtime analysis). Wide-ranging multi-source
      queries often return unmanageably large result sets, requiring non-traditional
      approaches to exclude extraneous data. RESULTS: Target Informatics Net (TINet) is
      a readily extensible data integration system developed at GlaxoSmith- Kline
      (GSK), based on the Object-Protocol Model (OPM) multidatabase middleware system
      of Gene Logic Inc. Data sources currently integrated include: the Mouse Genome
      Database (MGD) and Gene Expression Database (GXD), GenBank, SwissProt, PubMed,
      GeneCards, the results of runtime BLAST and PROSITE searches, and GSK proprietary
      relational databases. Special-purpose class methods used to filter and augment
      query results include regular expression pattern-matching over BLAST HSP
      alignments and retrieving partial sequences derived from primary structure
      annotations. All data sources and methods are accessible through an SQL-like
      query language or a GUI, so that when new investigations arise no additional
      programming beyond query specification is required. The power and flexibility of
      this approach are illustrated in such integrated queries as: (1) 'find homologs
      in genomic sequence to all novel genes cloned and reported in the scientific
      literature within the past three months that are linked to the MeSH term
      'neoplasms"; (2) 'using a neuropeptide precursor query sequence, return only HSPs
      where the target genomic sequences conserve the G[KR][KR] motif at the
      appropriate points in the HSP alignment'; and (3) 'of the human genomic sequences
      annotated with exon boundaries in GenBank, return only those with valid putative
      donor/acceptor sites and start/stop codons'.

PMID- 11448878
TI  - Identifying the 3'-terminal exon in human DNA.
AB  - MOTIVATION: We present JTEF, a new program for finding 3' terminal exons in human
      DNA sequences. This program is based on quadratic discriminant analysis, a
      standard non-linear statistical pattern recognition method. The quadratic
      discriminant functions used for building the algorithm were trained on a set of
      3' terminal exons of type 3tuexon (those containing the true STOP codon).
      RESULTS: We showed that the average predictive accuracy of JTEF is higher than
      the presently available best programs (GenScan and Genemark.hmm) based on a test
      set of 65 human DNA sequences with 121 genes. In particular JTEF performs well on
      larger genomic contigs containing multiple genes and significant amounts of
      intergenic DNA. It will become a valuable tool for genome annotation and gene
      functional studies. AVAILABILITY: JTEF is available free for academic users on
      request from ftp://cshl.org/pub/science/mzhanglab/JTEF and will be made available
      through the World Wide Web (http://argon.cshl.org/).

PMID- 11448879
TI  - Identifying target sites for cooperatively binding factors.
AB  - MOTIVATION: Transcriptional activation in eukaryotic organisms normally requires
      combinatorial interactions of multiple transcription factors. Though several
      methods exist for identification of individual protein binding site patterns in
      DNA sequences, there are few methods for discovery of binding site patterns for
      cooperatively acting factors. Here we present an algorithm, Co-Bind (for
      COperative BINDing), for discovering DNA target sites for cooperatively acting
      transcription factors. The method utilizes a Gibbs sampling strategy to model the
      cooperativity between two transcription factors and defines position weight
      matrices for the binding sites. Sequences from both the training set and the
      entire genome are taken into account, in order to discriminate against commonly
      occurring patterns in the genome, and produce patterns which are significant only
      in the training set. RESULTS: We have tested Co-Bind on semi-synthetic and real
      data sets to show it can efficiently identify DNA target site patterns for
      cooperatively binding transcription factors. In cases where binding site patterns
      are weak and cannot be identified by other available methods, Co-Bind, by virtue
      of modeling the cooperativity between factors, can identify those sites
      efficiently. Though developed to model protein-DNA interactions, the scope of Co
      Bind may be extended to combinatorial, sequence specific, interactions in other
      macromolecules. AVAILABILITY: The program is available upon request from the
      authors or may be downloaded from http://ural.wustl.edu.

PMID- 11448880
TI  - Conformational model for binding site recognition by the E.coli MetJ
      transcription factor.
AB  - MOTIVATION: Current methods for identifying sequence specific binding sites in
      DNA sequence using position specific weight matrices are limited in both
      sensitivity and specificity. Double strand DNA helix exhibits sequence dependent
      variations in conformation. Interactions between macromolecules result from
      complementarity of the two tertiary structures. We hypothesize that this
      conformational variation plays a role in transcription factor binding site
      recognition, and that the use of this structure information will improve the
      predictive power of transcription factor binding site models. RESULTS:
      Conformation models for the sequence dependence of DNA helix distortion have been
      developed. Using our conformational models, we defined a tertiary structure
      template for the met operon repressor MetJ binding site. Both naturally occurring
      sites and precursor binding sites identified through in vitro selection were used
      as the basis for template definition. The conformational model appears to
      recognize features of protein binding sites that are distinct from the features
      recognized by primary sequence based profiles. Combining the conformational model
      and primary sequence profile yields a hybrid model with improved discriminatory
      power compared with either the conformational model or sequence profile alone.
      Using our hybrid model, we searched the E.coli genome. We are able to identify
      the documented MetJ sites in the promoter regions of metA, metB, metC, metR and
      metF. In addition, we find several novel loci with characteristics suggesting
      that they are functional MetJ repressor binding sites. Novel MetJ binding sites
      are found upstream of the metK gene, as well as upstream of a gene, abc, a gene
      that encodes for a component of a multifunction transporter which may transport
      amino acids across the membrane. The false positive rate is significantly lower
      than the sequence profile method. AVAILABILITY: The programs of implementation of
      this algorithm are available upon request. The list of crystal structures used
      for compiling the mean base step parameters of DNA is available by anonymous ftp
      at http://stateslab.wustl.edu/pub/helix/StructureList.

PMID- 11448881
TI  - Automated image analysis for array hybridization experiments.
AB  - MOTIVATION: Image analysis is a major part of data evaluation for array
      hybridization experiments in molecular biology. The program presented here is
      designed to analyze automatically images from hybridization experiments with
      various arrangements: different kinds of probes (oligonucleotides or complex
      probes), different supports (nylon filters or glass slides), different labeling
      of probes (radioactively or fluorescently). The program is currently applied to
      oligonucleotide fingerprinting projects and complex hybridizations. The only
      precondition for the use of the program is that the targets are arrayed in a
      grid, which can be approximately transformed to an orthogonal equidistant grid by
      a projective mapping. RESULTS: We demonstrate that our program can cope with the
      following problems: global distortion of the grid, missing of grid nodes, local
      deviation of the spot from its specified grid position. This is checked by
      different quality measures. The image analysis of oligonucleotide fingerprint
      experiments on an entire genetic library is used, in clustering procedures, to
      group related clones together. The results show that the program yields
      automatically generated high quality input data for follow up analysis such as
      clustering procedures. AVAILABILITY: The executable files will be available upon
      request for academics.

PMID- 11448882
TI  - Semi-automated update and cleanup of structural RNA alignment databases.
AB  - We have developed a series of programs which assist in maintenance of structural
      RNA databases. A main program BLASTs the RNA database against GenBank and
      automatically extends and realigns the sequences to include the entire range of
      the RNA query sequences. After manual update of the database, other programs can
      examine base pair consistency and phylogenetic support. The output can be applied
      iteratively to refine the structural alignment of the RNA database. Using these
      tools, the number of potential misannotations per sequence was reduced from 20 to
      3 in the Signal Recognition Particle RNA database. AVAILABILITY: A quick-server
      and programs are available at http://www.bioinf.au.dk/rnadbtool/

PMID- 11448883
TI  - Evaluation of methods for the prediction of membrane spanning regions.
AB  - MOTIVATION: A variety of tools are available to predict the topology of
      transmembrane proteins. To date no independent evaluation of the performance of
      these tools has been published. A better understanding of the strengths and
      weaknesses of the different tools would guide both the biologist and the
      bioinformatician to make better predictions of membrane protein topology.
      RESULTS: Here we present an evaluation of the performance of the currently best
      known and most widely used methods for the prediction of transmembrane regions in
      proteins. Our results show that TMHMM is currently the best performing
      transmembrane prediction program.

PMID- 11448884
TI  - An integrated system for high throughput TaqMan based SNP genotyping.
AB  - We have developed an integrated laboratory information system that allows the
      flexible handling of pedigree, phenotype and genotype information. Specifically,
      it includes client applications for an integrated data import from TaqMan typing
      files, Mendel checking, data export, handling of pedigree and phenotype
      information and analysis features. AVAILABILITY: The SQL source code, sources and
      binaries of the client applications (NT and Windows95/98 platforms) and
      additional documentation are available at http://www.mucosa.de/.

PMID- 11448885
TI  - MEDUSA: large scale automatic selection and visual assessment of PCR primer
      pairs.
AB  - MEDUSA is a tool for automatic selection and visual assessment of PCR primer
      pairs, developed to assist large scale gene expression analysis projects. The
      system allows specification of constraints of the location and distances between
      the primers in a pair. For instance, primers in coding, non-coding, exon/intron
      spanning regions might be selected. Medusa applies these constraints as a filter
      to primers predicted by three external programs, and displays the resulting
      primer pairs graphically in the Blixem (Sonnhammer and Durbin, COMPUT: Appl.
      Biosci. 10, 301-307, 1994;
      http://www.cgr.ki.se/cgr/groups/sonnhammer/Blixem.html) viewer. AVAILABILITY: The
      MEDUSA web server is available at http://www.cgr.ki.se/cgr/MEDUSA. The source
      code and user information are available at ftp://ftp.cgr.ki.se/pub/prog/medusa.

PMID- 11448886
TI  - Visualization of expression clusters using Sammon's non-linear mapping.
AB  - A method of exploratory analysis and visualization of multi-dimensional gene
      expression data using Sammon's Non-Linear Mapping (NLM) is presented.

PMID- 11448887
TI  - ADAPTSITE: detecting natural selection at single amino acid sites.
AB  - ADAPTSITE is a program package for detecting natural selection at single amino
      acid sites, using a multiple alignment of protein-coding sequences for a given
      phylogenetic tree. The program infers ancestral codons at all interior nodes, and
      computes the total numbers of synonymous (c(S)) and nonsynonymous (c(N))
      substitutions as well as the average numbers of synonymous (s(S)) and
      nonsynonymous (s(N)) sites for each codon site. The probabilities of occurrence
      of synonymous and nonsynonymous substitutions are approximated by s(S) / (s(S) +
      s(N)) and s(N) / (s(S) + s(N)), respectively. The null hypothesis of selective
      neutrality is tested for each codon site, assuming a binomial distribution for
      the probability of obtaining c(S) and c(N). AVAILABILITY: ADAPTSITE is available
      free of charge at the World-Wide Web sites
      http://mep.bio.psu.edu/adaptivevol.html and
      http://www.cib.nig.ac.jp/dda/yossuzuk/welcome.html. The package includes the
      source code written in C, binary files for UNIX operating systems, manual, and
      example files.

PMID- 11448888
TI  - PAL: an object-oriented programming library for molecular evolution and
      phylogenetics.
AB  - Phylogenetic Analysis Library (PAL) is a collection of Java classes for use in
      molecular evolution and phylogenetics. PAL provides a modular environment for the
      rapid construction of both special-purpose and general analysis programs. PAL
      version 1.1 consists of 145 public classes or interfaces in 13 packages,
      including classes for models of character evolution, maximum-likelihood
      estimation, and the coalescent, with a total of more than 27000 lines of code.
      The PAL project is set up as a collaborative project to facilitate contributions
      from other researchers. AVAILIABILTY: The program is free and is available at
      http://www.pal-project.org. It requires Java 1.1 or later. PAL is licensed under
      the GNU General Public License.

PMID- 11448889
TI  - T-REX: reconstructing and visualizing phylogenetic trees and reticulation
      networks.
AB  - T-REX (tree and reticulogram reconstruction) is an application to reconstruct
      phylogenetic trees and reticulation networks from distance matrices. The
      application includes a number of tree fitting methods like NJ, UNJ or ADDTREE
      which have been very popular in phylogenetic analysis. At the same time, the
      software comprises several new methods of phylogenetic analysis such as: tree
      reconstruction using weights, tree inference from incomplete distance matrices or
      modeling a reticulation network for a collection of objects or species. T-REX
      also allows the user to visualize obtained tree or network structures using
      Hierarchical, Radial or Axial types of tree drawing and manipulate them
      interactively. AVAILABILITY: T-REX is a freeware package available online at:
      http://www.fas.umontreal.ca/biol/casgrain/en/labo/t-rex

PMID- 11448890
TI  - A Java applet for visualizing protein-protein interaction.
AB  - A web applet for browsing protein-protein interactions was implemented. It
      enables the display of interaction relationships, based upon neighboring distance
      and biological function. AVAILABILITY: The Java applet is available at
      http://www.charite.de/bioinformatics

PMID- 11448891
TI  - Treating Hodgkin's disease with bispecific antibodies: Both patients and antibody
      are limiting.

PMID- 11448892
TI  - The unfulfilled promise of melanoma vaccines.

PMID- 11448893
TI  - Adjuvant systemic therapy for early breast cancer: progress and controversies.

PMID- 11448894
TI  - The Cooperative Breast Cancer Tissue Resource: archival tissue for the
      investigation of tumor markers.
AB  - Investigators continue to search for reliable markers of prognosis of breast
      cancer. For many analyses, laboratory techniques permit the use of archival
      paraffin-embedded tissue collected years previously and readily linked to
      clinical and follow-up information. Laboratory investigators have often expressed
      the need for such a tissue resource. We have developed a publicly available
      resource of archival breast cancer specimens. The pathological material has been
      collected and reviewed by investigators at four institutions and currently
      includes breast cancer specimens from more than 9300 cases. Institutional
      pathologists reviewed slides and blocks using a common protocol and coding
      scheme. Clinical information and details of follow-up came from data routinely
      collected by the institutions' cancer registries. Coded data are maintained
      centrally in a single database. A subset of the data may be searched on the World
      Wide Web to determine the availability of cases with specified characteristics.
      The material collected by this Cooperative Breast Cancer Tissue Resource is
      generally representative of breast cancer diagnosed in community hospital
      settings in the United States. Seventy-two percent of the living cases have been
      followed for at least 5 years, and follow-up status is updated regularly.
      Interested laboratory investigators may apply to the Resource for the use of
      these tissues. This Resource is proving valuable to laboratory investigators who
      require large numbers of specimens for validation studies of prognostic markers
      of breast cancer.

PMID- 11448895
TI  - Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell
      lung cancer Is correlated with survival.
AB  - The prognostic role of epidermal growth factor receptor (EGFR) and HER2-neu
      remains controversial in patients with non-small cell lung cancer (NSCLC). We
      studied the association between the mRNA expression of EGFR, HER2-neu, and
      survival in primary tumor and matching nonmalignant tissues from 83 patients with
      NSCLC. Analysis was performed using a quantitative real-time PCR system (Taqman).
      EGFR and HER2-neu mRNA expression was detectable in all (100%) specimens
      analyzed. Twenty-nine (34.9%) patients had high HER2-neu expression, and 28
      (33.7%) patients had high EGFR expression. A high HER2-neu and EGFR coexpression
      was detectable in 14 (16.9%) patients. High HER2-neu expression was associated
      with inferior survival (P = 0.004), whereas high EGFR expression showed a trend
      toward inferior survival (P = 0.176). The impact of HER2-neu and EGFR
      coexpression on patients' survival was additive (P = 0.003). Multivariate
      analysis determined high HER2-neu expression (P = 0.041), and high EGFR/HER2-neu
      coexpression (P = 0.030) as significant and independent unfavorable prognostic
      factors. These findings indicate that HER2-neu and EGFR play a crucial role in
      the biological behavior of NSCLCs. Testing of molecular marker coexpression (EGFR
      and HER2-neu) improves the estimation of prognosis and appears to define low- and
      high-risk groups for treatment failure in curatively resected NSCLC.

PMID- 11448896
TI  - Circulating Epstein-Barr virus DNA in the serum of patients with gastric
      carcinoma.
AB  - PURPOSE: We investigated the detectability of EBV DNA in the serum of gastric
      carcinoma patients in Hong Kong. Previous data have shown that approximately 10%
      of gastric carcinomas in Hong Kong are associated with EBV. EXPERIMENTAL DESIGN:
      We recruited 51 patients with gastric carcinoma, 30 patients with gastritis, and
      197 apparently healthy controls. For gastric carcinoma patients, blood samples
      were obtained before surgery. After surgery, the resected tumor samples from the
      cancer cases were subjected to in situ hybridization for small EBV-encoded RNA
      (EBER). Serum EBV DNA in all cases was measured by real-time quantitative PCR.
      RESULTS: Serum EBV DNA was detectable in 5 of 5 (100%) EBER-positive gastric
      carcinoma cases (median concentration, 1063 copies/ml), in 13 of 14 (93%) EBER
      negative gastric carcinoma cases with EBER-positive infiltrating lymphocytes
      (median concentration, 50 copies/ml), and in 0 of 32 (0%) EBER-negative cases. In
      the nontumor controls, serum EBV DNA was detectable in 7 of 30 (23%) gastritis
      cases (median concentration, 0 copies/ml) and in 7 of 197 (3.6%) apparently
      healthy individuals (median concentration, 0 copy/ml). CONCLUSIONS: Our data
      indicate that serum EBV DNA reflects tumoral EBER status and opens up the
      possibility that circulating EBV DNA may be used as a tumor marker for the EBER
      positive gastric carcinomas. The biological and clinical significance of the
      presence of low levels of circulating EBV DNA in the minority of gastritis
      patients and healthy individuals remains to be elucidated.

PMID- 11448897
TI  - Profiling clonality and progression in multiple premalignant and malignant oral
      lesions identifies a subgroup of cases with a distinct presentation of squamous
      cell carcinoma.
AB  - A cohort of head and neck cancer patients, without exposure to tobacco and
      alcohol, presented with multiple preneoplastic and neoplastic lesions, the
      natural history of which may span several decades. Examination of these cases
      provides an opportunity to study the relationship between genetic, morphological,
      and clonal progression in these fields and establish whether they represent a
      unique presentation of squamous cell carcinoma. The presence of a common novel
      microsatellite allele, a common breakpoint or concordant allelic imbalance at
      multiple loci, reveals that a high proportion of these serial lesions arise due
      to spread of a precursor. The tumors arising in these patients were typically
      nonaggressive, although metastases developed at a late stage, supporting the
      notion that the genotype results in a phenotype with a propensity for lateral
      spread, rather than invasion. Different genetic aberrations were detected in
      morphologically similar phenotypes such that no consistent early or late events
      were associated with development of premalignant lesions. Combining information
      about the clinicopathological features and histological examination of the
      margins with that derived from clonality analysis reveals that a subgroup of
      patients, without exposure to the traditional risk factors associated with this
      disease, developed multiple clonally related oral lesions and represents a unique
      presentation of head and neck squamous cell carcinoma. We suggest the term clonal
      cancerization to describe multiple premalignant and malignant lesions when there
      is conclusive evidence that they arise due to lateral spread from a common
      precursor.

PMID- 11448898
TI  - Protein binding alters the activity of suramin, carboxyamidotriazole, and UCN-01
      in an ex vivo rat aortic ring angiogenesis assay.
AB  - Angiogenesis inhibitors are currently in clinical development for cancer. These
      agents pose unique developmental challenges: (a) determining maximum biological
      doses versus maximum tolerated doses; (b) defining response criteria other than
      objective tumor responses; and (c) defining safe regimens for prolonged, chronic
      administration. The current in vitro angiogenesis assays used in the screening
      and preclinical development of antiangiogenic agents each have their own
      advantages and disadvantages, yet all seem to underestimate the importance and
      impact of in vivo protein-drug interactions. We have developed a human serum rat
      aortic ring angiogenesis bioassay that highlights protein binding concerns using
      three anticancer agents that have documented antiangiogenic activity: suramin,
      carboxyamidotriazole, and 7-hydroxystaurosporine. We have determined that the
      bioassay concentrations of suramin (100 microg/ml) and 7-hydroxystaurosporine (>
      1 microg/ml), but not carboxyamidotriazole (> or = 60 microg/ml), that inhibit
      microvessel formation are consistent with target plasma levels achievable in the
      clinic. We conclude that assays such as the human serum rat aortic ring bioassay
      may prove useful in predicting the concentrations of protein-bound antiangiogenic
      agents required for free fraction biological activity.

PMID- 11448899
TI  - Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: role of
      infusion schedule and costimulation with cytokines.
AB  - The natural killer cell-activating anti-CD16/CD30 bispecific monoclonal antibody
      (BiMAb) had shown efficacy in a Phase I/II trial of refractory Hodgkin's disease
      (HD). To gain additional information on clinical efficacy and to investigate the
      effects of different application schedules and the concomitant application of
      cytokines, we performed a second randomized pilot trial using this BiMAb in
      patients with refractory HD. Patients received 4 x 25 mg HRS-3/A9 either as a
      continuous infusion for 4 days or as a 1-h infusion every other day. In case of
      an objective response, retreatment was attempted after 4 weeks; in case of stable
      disease (SD), a second course was given after prestimulation with interleukin 2
      and followed by granulocyte macrophage colony-stimulating factor s.c. A total of
      16 heavily pretreated patients received one to four BiMAb courses. Overall, we
      observed one complete remission and three partial remissions lasting 5-9 months
      (three of four of these responses occurred after continuous BiMAb infusion) and
      four cases of SD for 3 to >6 months. Interleukin 2 pretreatment before the second
      BiMAb course resulted in a significant increase of circulating natural killer
      cells in all five patients treated. This coincided with the conversion of two
      cases of SD into one complete remission and one partial remission. HRS-3/A9
      related side effects consisted of mild fever in only six patients. In summary,
      this second trial confirmed the antitumor efficacy of this BiMAb against HD and
      the minor toxicity of this BiMAb. Coadministration of cytokines might contribute
      to an augmented antitumor activity, and additional clinical trials are warranted
      to optimize this novel treatment modality.

PMID- 11448900
TI  - Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine.
AB  - A polyvalent melanoma vaccine prepared from shed antigens stimulates humoral and
      cellular immune responses and improves survival compared with historical
      controls. We conducted a double-blind, prospectively randomized, placebo
      controlled trial to assess whether this vaccine could slow the progression of
      resected melanoma. Thirty-eight patients with resected melanoma metastatic to
      regional nodes (American Joint Committee on Cancer stage III) who had a
      particularly poor prognosis on the basis of the nodes being clinically positive
      or two or more histologically positive nodes were randomly assigned in a 2:1
      ratio to treatment with 40 microg of melanoma or placebo (human albumin) vaccine,
      both of which were bound to alum as an adjuvant. Immunizations were given
      intradermally into the extremities every 3 weeks x 4, monthly x 3, every 3 months
      x 2, and then every 6 months for 5 years or until disease progression. Twenty
      four patients were treated with the melanoma, and 14 patients were treated with
      the placebo vaccine. The groups were evenly balanced with respect to prognostic
      factors. Median length of observation was 2.5 years. There was no local or
      systemic toxicity. By Kaplan-Meier analysis, median time to disease progression
      was two and a half times longer in patients treated with melanoma vaccine
      compared with that in patients treated with placebo vaccine, i.e., 1.6 years (95%
      confidence interval, 1.0-3.0 years) compared with 0.6 year [95% confidence
      interval, 0.3-1.9 year(s)]. By Cox proportional hazards analysis, this difference
      was significant at P = 0.03. Overall survival was 40% longer in the melanoma
      vaccine-treated group (median overall survival of 3.8 years versus 2.7 years),
      but this difference was not statistically significant. In a double-blind and
      placebo-controlled trial, these results suggest that immunization with a melanoma
      vaccine may be able to slow the progression of melanoma. Although statistically
      significant, these results must be interpreted with caution because they are
      based on a small number of patients.

PMID- 11448901
TI  - A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in
      patients with androgen-independent prostate cancer.
AB  - PURPOSE: Thalidomide is a potent teratogen that causes dysmelia in humans.
      Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer
      is dependent on the recruitment of new blood vessels to grow and metastasize.
      Based on those data, we initiated a Phase II trial of thalidomide in patients
      with metastatic androgen-independent prostate cancer. EXPERIMENTAL DESIGN: This
      was an open-label, randomized Phase II study. Thalidomide was administered either
      at a dose of 200 mg/day (low-dose arm) or at an initial dose of 200 mg/day that
      escalated to 1200 mg/day (high-dose arm). RESULTS: A total of 63 patients were
      enrolled onto the study (50 patients on the low-dose arm and 13 patients on the
      high-dose arm). Serum prostate-specific antigen (PSA) decline of > or = 50% was
      noted in 18% of patients on the low-dose arm and in none of the patients on the
      high-dose arm. Four patients were maintained for > 150 days. The most prevalent
      complications were constipation, fatigue, neurocortical, and neurosensory.
      CONCLUSION: Thalidomide, an antiangiogenesis agent, has some activity in patients
      with metastatic prostate cancer who have failed multiple therapies. A total of
      27% of all patients had a decline in PSA of > or = 40%, often associated with an
      improvement of clinical symptoms. Because our preclinical studies had shown that
      thalidomide increases PSA secretion, we believe that the magnitude of PSA decline
      seen in our trial justifies further study.

PMID- 11448902
TI  - Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients
      with colorectal cancer.
AB  - Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent
      colon cancer in rodents. In view of the sparse information on the
      pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation
      pilot study of a novel standardized Curcuma extract in proprietary capsule form
      was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of
      curcumin. Fifteen patients with advanced colorectal cancer refractory to standard
      chemotherapies received Curcuma extract daily for up to 4 months. Activity of
      glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by
      malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis,
      were measured in patients' blood cells. Oral Curcuma extract was well tolerated,
      and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites
      were detected in blood or urine, but curcumin was recovered from feces. Curcumin
      sulfate was identified in the feces of one patient. Ingestion of 440 mg of
      Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic
      glutathione S-transferase activity. At higher dose levels, this effect was not
      observed. Leukocytic M(1)G levels were constant within each patient and
      unaffected by treatment. Radiologically stable disease was demonstrated in five
      patients for 2-4 months of treatment. The results suggest that (a) Curcuma
      extract can be administered safely to patients at doses of up to 2.2 g daily,
      equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in
      humans and may undergo intestinal metabolism; and (c) larger clinical trials of
      Curcuma extract are merited.

PMID- 11448903
TI  - A phase I and pharmacokinetic study of 1843U89, a noncompetitive inhibitor of
      thymidylate synthase, in patients with advanced solid malignancies.
AB  - This study was performed to assess the feasibility of administering 1843U89, a
      potent, noncompetitive inhibitor of thymidylate synthase that does not require
      polyglutamation for activity, as a 2-min i.v. infusion daily for 5 days every 3
      weeks, to determine whether folic acid supplementation ameliorates the toxic
      effects of 1843U89 and permits further dose escalation, and to recommend doses of
      1843U89 administered without and with folic acid for further clinical
      evaluations. The study also sought to characterize the pharmacokinetic behavior
      of 1843U89 and to seek preliminary evidence of anticancer activity. Patients with
      advanced solid malignancies were treated with escalating doses of 1843U89 as a 2
      min i.v. infusion daily for 5 days every 3 weeks. Initially, patients were
      treated in the absence of high-dose folic acid until dose-limiting toxicity was
      consistently noted. Next, patients were treated with escalating doses of 1843U89
      preceded by 1000 mg of folic acid administered p.o. 30 min before each of the 5
      daily doses of 1843U89. Patients (32) received 101 total courses of 1843U89 at
      doses ranging from 1 to 6 mg/m(2)/day with and without folic acid. At the 2
      mg/m(2)/day dose level without folic acid, 2 of 7 new patients experienced dose
      limiting toxicity, principally neutropenia, mucositis, and malaise in 3 of 11
      courses. 1843U89 doses were further increased with folic acid to 6 mg/m(2)/day,
      but repetitive treatment was not feasible at this dose level because of an
      unacceptable high incidence of severe neutropenia and mucositis. Other toxicities
      included thrombocytopenia, rash, and fever. In contrast, repetitive treatment at
      the 5 mg/m(2)/day dose level was feasible. The pharmacokinetics of 1843U89 were
      neither dose dependent nor affected by folic acid. On day 1, clearance, terminal
      half-life, and steady-state volume of distribution values averaged 47.1 +/- 21.7
      ml/min/m(2), 7.72 +/- 4.09 h, and 16.7 +/- 8.8 liter/m(2)/h, respectively. The
      results of the study indicate that the administration of 1843U89 as a 2-min
      infusion daily for 5 days every 3 weeks without and with folic acid is feasible
      at 1843U89 doses as high as 2 and 5 mg/m(2)/day, respectively. Because folic acid
      pretreatment results in no diminution of the antitumor activity of 1843U89 in
      preclinical studies and ameliorates the toxic effects of 1843U89 in both
      preclinical models and cancer patients, the therapeutic index of 1843U89 may be
      enhanced by folic acid pretreatment and, therefore, the development of 1843U89
      with folic acid is warranted. However, the question of whether to administer
      1843U89 at a dose of 2 mg/m(2)/day with folic acid, which is associated with
      negligible toxicity, or at its highest feasible dose with folic acid, 5
      mg/m(2)/day, should be addressed in appropriately designed trials.

PMID- 11448904
TI  - Phase I and pharmacological study of the oral matrix metalloproteinase inhibitor,
      MMI270 (CGS27023A), in patients with advanced solid cancer.
AB  - This Phase I study of MMI270, an p.o. administered matrix metalloproteinase
      inhibitor, assessed toxicity, pharmacokinetics, and tumor response data and
      investigated markers of biological activity to recommend a dose for Phase II
      studies. MMI270 was administered continuously at seven dose levels (50 mg once
      daily to 600 mg three times/day). Patients were evaluated for toxicity and tumor
      response, and blood and urine samples were taken for pharmacokinetics, bone
      resorption markers, direct targets of the inhibitor [matrix metalloproteinase-2
      (MMP-2), MMP-8, and MMP-9], indirect targets [tissue inhibitor of
      metalloproteinase-1 (TIMP-1), TIMP-2, basic fibroblast growth factor, vascular
      endothelial growth factor, vascular cell adhesion molecule-1, soluble urokinase
      plasminogen activator receptor, and cathepsins B and H] and for a tumor necrosis
      factor-alpha cytokine release assay. Ninety-two patients were entered. There was
      no myelotoxicity. Eighteen patients developed a widespread maculopapular rash,
      which increased in frequency and severity at doses > or = 300 mg bid. Thirty nine
      patients developed musculoskeletal side effects, which were related to duration
      of treatment, not to dose level. Pharmacokinetics were linear, and MMI270 was
      rapidly absorbed and eliminated with minimal accumulation on chronic dosing.
      Sustained plasma concentrations in excess of 4 x mean IC(50) for the target
      enzymes were observed at dose levels > or = 150 mg bid. There were no tumor
      regressions; however, 19 patients had stable disease for > or = 90 days. There
      was a dose-response increase of MMP-2 and TIMP-1 with MMI270. Transient effects
      on the bone resorption markers were detected. MMI270 was generally well
      tolerated, with adequate plasma levels for target enzyme inhibition. The two main
      toxicities were rash, resulting in a maximum tolerated dose of 300 mg bid and
      musculoskeletal side effects. Biological marker data indicate drug effects. The
      rise in TIMP-1 suggests that a reflex rise in inhibitors could modify the effects
      of MMI270. The recommended Phase II dose is 300 mg bid.

PMID- 11448905
TI  - Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type
      gastric adenocarcinoma.
AB  - PURPOSE: Cyclooxygenase (Cox) is the key enzyme in conversion of arachidonic acid
      to prostanoids. Two Cox genes have been cloned, and expression of Cox-2 mRNA and
      protein has been shown to be elevated in several human malignancies and in animal
      models of carcinogenesis. The purpose of this study was to investigate Cox-2
      protein expression in human gastric dysplasias and adenocarcinomas. EXPERIMENTAL
      DESIGN: Performance of several Cox-2 antibodies was evaluated, after which Cox-2
      protein expression was studied in 67 gastric cancer specimens and in eight
      definitive dysplasias by using immunohistochemistry. RESULTS: Cox-2 positivity
      was detected in 58% (25/43) of the intestinal-type (well-differentiated) tumors
      and 6% (1/18) of diffuse-type (poorly differentiated) tumors. Consistent with
      these data, we detected higher expression of Cox-2 mRNA, protein, and enzymatic
      activity in well-differentiated gastric cancer cell lines (MKN-28 and MKN-74)
      when compared with poorly differentiated cell lines (HSC-39 and KATO III). Cox-2
      immunoreactivity was localized to the carcinoma cells, but the stroma of the
      tumors was negative. However, strong Cox-2 positivity was consistently detected
      in stromal cells at sites of erosions and ulcerations. Furthermore, four of nine
      (44%) definitive dysplasias of the stomach that showed no evidence of invasion
      were positive for Cox-2. CONCLUSIONS: Cox-2 is expressed by the neoplastic cells
      in the intestinal-type gastric adenocarcinoma and by precarcinogenic (dysplastic)
      lesions leading to this disease.

PMID- 11448906
TI  - Prognostic significance of plasma vascular endothelial growth factor levels in
      patients with hormone-refractory prostate cancer treated on Cancer and Leukemia
      Group B 9480.
AB  - PURPOSE: Plasma vascular endothelial growth factor (VEGF) levels are
      significantly elevated in patients with hormone-refractory prostate cancer (HRPC)
      compared with patients with localized disease and have been associated with
      disease progression in other cancer patient populations. Therefore, we measured
      VEGF levels in plasma prospectively collected from patients enrolled in Cancer
      and Leukemia Group B 9480, an intergroup study of suramin in patients with HRPC,
      to determine whether these levels had prognostic significance. EXPERIMENTAL
      DESIGN: Pretreatment plasma was collected from patients with HRPC enrolled in
      Cancer and Leukemia Group B 9480. In a subset of samples representative of the
      entire cohort, plasma VEGF levels were determined in duplicate using a Quantiglo
      chemiluminescent ELISA kit (R&D Systems, Minneapolis, MN). Statistical analyses
      were performed to determine the correlation between pretreatment plasma VEGF
      levels and time of overall survival. The proportional hazards model was used to
      assess the prognostic significance of various cut points in multivariate models.
      RESULTS: Plasma VEGF levels in this population ranged from 4-885 pg/ml, with a
      median level of 83 pg/ml. As a continuous variable, plasma VEGF levels inversely
      correlated with survival time (P = 0.002). Using various exploratory cut points,
      plasma VEGF levels appeared to correlate with survival. In multivariate models in
      which other prognostic factors (serum prostate-specific antigen, alkaline
      phosphatase, evidence of measurable disease, and hemoglobin) were included,
      plasma VEGF levels were significant at various cut points tested. CONCLUSION:
      Although these data are exploratory and need to be confirmed in an independent
      data set, they suggest that VEGF may have clinical significance in patients with
      HRPC.

PMID- 11448907
TI  - Breast tumor immunophenotype of BRCA1-mutation carriers is influenced by age at
      diagnosis.
AB  - PURPOSE: Breast tumors of BRCA1 mutation carriers and those of early onset breast
      cancer cases share similar histological features, being generally high-grade,
      highly proliferative, aneuploid tumors that are predominantly estrogen- and
      progesterone-receptor negative. Because histological features of tumors of
      premenopausal women differ from those of tumors of older women, we sought to
      determine whether the immunophenotype of breast tumors of BRCA1 mutation carriers
      was influenced by age at diagnosis. EXPERIMENTAL DESIGN: We examined 31 breast
      tumors from BRCA1 mutation carriers and compared them with 81 tumors of age
      matched (plus or minus 5 years) breast cancer patients unselected for family
      history. Tumors were further matched for histology, grade, and size. Paraffin
      embedded tumor tissues were examined for protein expression of estrogen receptor
      (ER), PR, Ki-67, cyclin D1, TP53, HER2, beta-catenin, and cyclin E using
      immunohistochemical approaches. RESULTS: ER (P = 0.01), PR (P = 0.06), and cyclin
      D1 (P = 0.002) were less frequently expressed and Ki-67 (P = 0.01) and beta
      catenin (P = 0.04) were more frequently expressed in tumors of BRCA1 mutation
      carriers than controls. After age stratification, we found a significant
      difference in the frequency of tumors of BRCA1 mutation carriers diagnosed before
      50 years of age compared with age-matched controls that stained positive for ER
      (P = 0.01), PR (P = 0.03), Ki-67 (P = 0.008), cyclin D1 (P < 0.001), HER2 (P =
      0.04), and beta-catenin (P = 0.05). However, no significant differences were
      observed in tumors of BRCA1 mutation carriers diagnosed at age 50 or older
      compared with age-matched controls. CONCLUSIONS: These data suggest that age at
      diagnosis, possibly related to menopausal status, may be an important factor in
      the expression of specific proteins in breast tumors of BRCA1 mutation carriers.

PMID- 11448908
TI  - Induction of interleukin-8 by Epstein-Barr virus latent membrane protein-1 and
      its correlation to angiogenesis in nasopharyngeal carcinoma.
AB  - PURPOSE: The EBV latent membrane protein-1 (LMP-1) is a multifunctional protein.
      Recently, the contribution of LMP-1 to the metastasis of nasopharyngeal carcinoma
      (NPC) has been suggested. Angiogenesis is a key step for metastasis. Thus, the
      association of LMP-1 to neovascularization of NPC was examined in this study.
      EXPERIMENTAL DESIGN: The association of LMP-1 to angiogenesis in 39 patients with
      NPC was evaluated by immunohistochemical study, and then induction of angiogenic
      factors by LMP-1 was examined by ELISA and luciferase reporter assay. RESULTS: In
      an immunohistochemical study, the expression of LMP-1 was significantly
      correlated to microvessel counts (P = 0.0003), suggesting that LMP-1 may induce
      some angiogenic factors. Therefore, we studied the relationship between LMP-1
      expression and interleukin-8 (IL-8), vascular endothelial growth factor (VEGF),
      and basic fibroblast growth factor (bFGF) expression by immunohistochemical
      analysis. IL-8, VEGF, and bFGF expression were correlated to microvessel counts,
      but only IL-8 expression was significantly correlated to LMP-1 expression (P <
      0.0001). Transfection with LMP-1 expression plasmid induced IL-8 protein
      expression in C33A cells. The expression of LMP-1 transactivated IL-8 promoter,
      as demonstrated by IL-8 promoter luciferase reporter assay. Mutation of the
      nuclear factor kappaB responsive element in the IL-8 promoter region completely
      abolished transactivation by LMP-1, whereas mutation of the activator protein
      responsive element did not affect promoter activity. CONCLUSION: These results
      suggested that LMP-1 induces expression of IL-8 through the nuclear factor kappaB
      binding site, which may contribute in part to angiogenesis in NPC.

PMID- 11448909
TI  - A novel single-nucleotide polymorphism in the 3'-untranslated region of the human
      dihydrofolate reductase gene with enhanced expression.
AB  - A novel single-nucleotide polymorphism (SNP), 829C-->T in the 3'-untranslated
      region of the human dihydrofolate reductase (DHFR) gene transcript, was
      identified in the study population of 37 patients with childhood
      leukemias/lymphomas and 83 healthy Japanese children. Frequencies of the DHFR
      829C/C, 829C/T, and 829T/T genotypes were 83.8, 10.8, and 5.4%, respectively, in
      the cases and 74.7, 19.3, and 6.0% in the controls, showing no significant
      difference in genotype frequencies between the cases and controls. When
      determined by real-time quantitative reverse transcription-PCR analysis, the
      highest expression of the DHFR transcript was demonstrated in the samples with a
      DHFR 829T/T polymorphism (P < 0.001). Direct association of the presence of the
      SNP with methotrexate-related adverse events in each patient was not demonstrated
      in this limited analysis. These data suggest that the novel DHFR 829 polymorphism
      is associated with a positive role in gene expression and provide evidence of a
      functional SNP in the 3' regulatory region of the gene.

PMID- 11448910
TI  - Expression profiles of ErbB family receptors and prognosis in primary
      transitional cell carcinoma of the urinary bladder.
AB  - In vitro experiments have demonstrated that epidermal growth factor (EGF)-related
      peptides activate distinct subsets of ErbB receptors and differ in their
      biological activities. The implications of cross-talk among ErbB family receptors
      in human cancer, however, remain to be clarified. This cohort study was performed
      to examine the expression patterns of ErbB receptors by immunohistochemistry in
      primary human bladder cancer (n = 245) and compared with conventional biological
      indicators for their prognostic significance. Expression of individual EGF
      receptor (EGFR) and ErbB2, ErbB3, or ErbB4 receptors was detected in 72.2, 44.5,
      56.3, and 29.8% of bladder cancer cases, respectively. Expression of two of the
      receptors varied from 14.7 to 42.4%, of three of the receptors between 11.0 and
      22.0%, and of all four of the ErbB receptors by 8.6%. Important indicators in
      association with patient survival were tumor staging (P = 0.017), ErbB2 (P =
      0.018), EGFR-ErbB2 (P = 0.023), and ErbB2-ErbB3 (P = 0.042). In the subset of
      grade-2 tumors, EGFR-ErbB2-ErbB3 and EGFR-ErbB2 predicted the development of
      second recurrence (P = 0.026 and 0.039, respectively), and ErbB2-ErbB3 tended to
      correlate with patient survival (P = 0.09). The results indicate that a
      combination of EGFR, ErbB2, and ErbB3 expression profile may be a better
      prognostic indicator than any family member alone. Given that ErbB2 is the
      preferred coexpression partner of ErbB family members, expression of other ErbB
      receptors may significantly affect the prognostic implication of ErbB2 for
      bladder cancer patients.

PMID- 11448911
TI  - Allelic losses in OraTest-directed biopsies of patients with prior upper
      aerodigestive tract malignancy.
AB  - Genetic alterations at critical chromosome loci have been shown to be predictors
      of the progression of oral premalignancy-to-invasive cancer. We obtained a unique
      group of oral biopsies, initially collected during a prospective study designed
      to test the ability of OraTest (toluidine blue), to identify recurrent oral
      neoplastic lesions in patients with definite therapy for head and neck or upper
      aerodigestive tract (UADT) cancer. A total of 46 cases, including 13 squamous
      cell carcinoma (SCC), 11 carcinoma-in situ or dysplasia, and 22 morphologically
      normal oral biopsies, were analyzed for loss of heterozygosity (LOH) at 9p21,
      3p21, and 17p13(TP53) by microsatellite analysis. LOH at one or more tested
      markers in at least one biopsy was detected in 76% (35 of 46) cases. All of the
      SCC and carcinoma-in situ cases showed LOH, and, strikingly, more than one-half
      (69%, 13 of 22) of morphologically normal epithelia also harbored LOH in at least
      one tested marker. The most frequent LOH was found on chromosome 9p21 (69%, 31 of
      45). LOH was observed at 3p21, 17p13(TP53), or in multiple chromosomal arms
      significantly more often in SCC than in normal epithelia. In the majority of
      cases, two oral biopsies, one from an OraTest-staining positive area and another
      from a negative area adjacent to the stain, were collected. Among 25 LOH positive
      cases with two biopsies, identical allelic losses were confirmed between stained
      and nonstained biopsies in 16 cases. In the remaining nine cases with discordant
      LOH patterns between two biopsies, eight cases showed LOH at more genetic loci in
      OraTest-stained areas. Our data confirm that clonal genetic alterations,
      especially 9p21 deletion, are often present in the oral epithelia of patients
      with previous UADT malignancy and, combined with previous studies, suggest that
      genetic analysis will help stratify patients at risk of developing a secondary
      oral cancer. In addition to detecting cancer, our study suggests that OraTest can
      detect clinically occult lesions in the progression pathway to oral cancer.

PMID- 11448912
TI  - Combined automatic immunological and molecular cytogenetic analysis allows exact
      identification and quantification of tumor cells in the bone marrow.
AB  - PURPOSE: To improve the detection of disseminated tumor cells in bone marrow (BM)
      and peripheral blood samples of solid tumor patients, a novel computer-assisted
      scanning system for automatic search, image analysis, and repositioning of these
      cells was developed. This system allows precise identification and quantification
      of tumor cells by sequential immunological and molecular cytogenetic analysis. In
      this study, we attempt to demonstrate the practical use of this approach by
      analyzing BM samples from neuroblastoma patients. EXPERIMENTAL DESIGN: The
      disialo-ganglioside (GD2) molecule was used as the immunological target. The GD2
      molecule was described as being specific for neuroblastoma cells, although false
      positive reactions had been suspected. To verify or disprove the neoplastic
      nature of the immunologically positive cells, sequential fluorescence in situ
      hybridization was performed on these cells to search for those genetic
      aberrations found in the corresponding primary tumors. A total of 115 samples
      from 40 newly diagnosed patients were evaluated for the presence of GD2(+) cells
      in the BM. RESULTS: GD2 positivity was detected in 95.2% of stage 4 patients, in
      100% of stage 4s patients, and in 38.5% of patients with localized/regional
      disease. In stage 4 and 4s BM samples, the GD2(+) cells were unequivocally
      identified as tumor cells based on the molecular cytogenetic aberrations found by
      fluorescence in situ hybridization. However, in BM samples from patients with
      localized/regional disease, all GD2(+) cells were concluded to represent false
      positivity due to the absence of genetic aberrations. CONCLUSIONS: Automatic
      search and sequential molecular cytogenetic analysis of the immunologically
      positive cells provide precise information on both the number and cytogenetic
      profile of disseminated tumor cells.

PMID- 11448913
TI  - Diagnosis of pancreatic adenocarcinoma by detection of human telomerase reverse
      transcriptase messenger RNA in pancreatic juice with sample qualification.
AB  - PURPOSE: We evaluated the diagnostic efficacy of detection of human telomerase
      reverse transcriptase (hTERT) message, a catalytic domain of human telomerase, in
      endoscopic retrograde pancreatography (ERP)-derived pancreatic juice.
      EXPERIMENTAL DESIGN: Both hTERT and CD25 expression were detected by reverse
      transcription-PCR (RT-PCR) in 17 patients with pancreatic adenocarcinoma (PC), 12
      patients with chronic pancreatitis (CP), and 7 patients with no ERP abnormality
      (N). In the same patients, beta-actin message was semiquantified by competitive
      RT-PCR. K-ras codon 12 mutations were concomitantly analyzed by enriched PCR-SSCP
      in 11 and 7 PC and CP cases, respectively. RESULTS: Expression of hTERT was
      detected in 88% of PC cases and 17% of CP cases but not in the normal control
      (N). Alterations in K-ras were detected in 73% of PC cases and 57% of CP cases,
      respectively. beta-Actin mRNA was expressed in >3.0 x 10(1) copies/microl in all
      but two PC cases in which hTERT mRNA was not detected. CD25-positive and 
      negative peripheral lymphocytes were isolated from a normal volunteer using a
      fluorescent activating cell sorter. The hTERT message was detected in CD25
      positive peripheral lymphocytes and in 18, 25, and 0% of the pancreatic juice
      samples from PC, CP, and N cases, respectively. All CP cases expressing hTERT
      message were also CD25 positive. CONCLUSIONS: These results suggest that
      detection of hTERT mRNA in pancreatic juice is a powerful tool to discriminate PC
      from CP, particularly when the samples are qualified against beta-actin mRNA
      levels and contaminating CD25-positive lymphocytes.

PMID- 11448914
TI  - Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix.
AB  - Promoter hypermethylation is an important pathway for the repression of gene
      transcription in cancer. We investigated promoter hypermethylation of six genes,
      p16, APC, HIC-1, death-associated protein kinase (DAPK), O(6)-methylguanine-DNA
      methyltransferase (MGMT), and E-cadherin, in uterine cervical carcinoma from 53
      patients including 31 cases of squamous cell carcinoma (SCC) and 22 cases of
      adenocarcinoma (AC). Aberrant methylation of at least one of these genes was
      detected in 79% (42 of 53) of cases including 71% (22 of 31) of SCC and 91% (20
      of 22) of AC cases. No aberrant methylation was detected in normal cervical
      tissue from 24 control hysterectomy specimens. There was no correlation between
      promoter hypermethylation at any gene and the presence of human papillomavirus-16
      or -18 E7 DNA. In AC cases, promoter hypermethylation of the APC and HIC-1 genes
      was detected at a statistically significant higher frequency than in the SCC
      cases (APC, 60% versus 13%, P < 0.001; HIC-1, 63% versus 32%, P < 0.03).
      Conversely, promoter hypermethylation of p16 and DAPK was more common in SCC
      cases than in AC cases. Our results suggest that promoter hypermethylation is a
      frequent epigenetic event in cervical carcinoma. The pattern of gene promoter
      hypermethylation is distinctly different between AC and SCC. The absence of these
      epigenetic alterations in normal cervical tissue suggests that they may also be
      valuable as cancer markers.

PMID- 11448915
TI  - Integrin-linked kinase expression increases with prostate tumor grade.
AB  - PURPOSE: Integrin-linked kinase (ILK) overexpression can suppress anoikis,
      promote anchorage-independent cell cycle progression, and induce tumorigenesis
      and invasion. Inhibition of ILK in prostatic adenocarcinoma (CaP) cells elicits
      cell cycle arrest and induces apoptosis. Furthermore, ILK expression increases
      with androgen-independent progression of human CaP cell lines, suggesting that
      increased ILK expression may be associated with CaP progression. EXPERIMENTAL
      DESIGN: To assess whether ILK expression may be related to CaP development and/or
      progression, we have evaluated ILK expression by immunohistochemistry in 100
      human prostate tissues. RESULTS: We show that ILK expression increases
      significantly with CaP progression. ILK immunostaining is specifically increased
      in high-grade, primary human CaP relative to adjacent benign prostatic
      hyperplasia (P < 0.001), benign prostatic hyperplasia from patients without
      cancer (P < 0.002), and low-grade CaP (P = 0.003). ILK overexpression is
      specifically associated with the increased proliferative index (P = 0.001) that
      typifies CaP progression. Strikingly, intense uniform ILK immunostaining was
      inversely related to 5-year patient survival (P = 0.004). CONCLUSIONS: ILK
      expression increases dramatically with CaP progression. ILK expression is also
      specifically related to the disproportionately increased proliferative index that
      contributes to the net gain of CaP cells during progression. Finally, enhanced
      ILK expression is inversely related to 5-year patient survival. These data
      therefore implicate increased ILK expression in prostate tumor progression.

PMID- 11448916
TI  - Soluble Tie2 and Flt1 extracellular domains in serum of patients with renal
      cancer and response to antiangiogenic therapy.
AB  - Antiangiogenesis drugs can be difficult to evaluate because they produce disease
      stabilization rather than tumor regression. Markers of endothelial mass in tumors
      may be of value to monitor therapy and evaluate such drugs. Soluble domains of
      the endothelial receptor tyrosine kinases, sTie2 (angiopoietin receptor) and
      sFlt1 (vascular endothelial growth factor receptor-1) were analyzed by sandwich
      ELISA in serum samples from 43 patients with advanced renal cancer before and 1
      month after antiangiogenic therapy with razoxane. Pretreatment sFlt1 levels were
      0.77 ng/ml +/- 0.48 (SD) and sTie2 74.3 ng/ml +/- 15 (SD). Pretreatment sFlt1
      levels above the median were associated with a lesser chance of stable disease (P
      = 0.04) and poorer survival (P = 0.01). Fall of sTie2 on treatment was associated
      with stable disease (P = 0.05) and improved survival (P = 0.04). The soluble
      receptors measured weeks before response were assessed and correlated with
      response and survival, showing they may be useful to monitor and develop
      antiangiogenic therapy.

PMID- 11448917
TI  - Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in
      breast and lung carcinomas.
AB  - The adenomatous polyposis coli (APC) gene is a tumor suppressor gene associated
      with both familial and sporadic cancer. Despite high rates of allelic loss in
      lung and breast cancers, point mutations of the APC gene are infrequent in these
      cancer types. Aberrant methylation of the APC promoter 1A occurs in some
      colorectal and gastric malignancies, and we investigated whether the same
      mechanism occurs in lung and breast cancers. The methylation status of the APC
      gene promoter 1A was analyzed in 77 breast, 50 small cell (SCLC), and 106 non
      small cell (NSCLC) lung cancer tumors and cell lines and in 68 nonmalignant
      tissues by methylation-specific PCR. Expression of the APC promoter 1A transcript
      was examined in a subset of cell lines by reverse transcription-PCR, and loss of
      heterozygosity at the gene locus was analyzed by the use of 12 microsatellite and
      polymorphic markers. Statistical tests were two-sided. Promoter 1A was methylated
      in 34 of 77 breast cancer tumors and cell lines (44%), in 56 of 106 NSCLC tumors
      and cell lines (53%), in 13 of 50 SCLC cell lines (26%), and in 3 of 68
      nonmalignant samples (4%). Most cell lines tested contained the unmethylated or
      methylated form exclusively. In 27 cell lines tested, there was complete
      concordance between promoter methylation and silencing of its transcript.
      Demethylation with 5-aza-2'-deoxycytidine treatment restored transcript 1A
      expression in all eight methylated cell lines tested. Loss of heterozygosity at
      the APC locus was observed in 85% of SCLCs, 83% of NSCLCs, and 63% of breast
      cancer cell lines. The frequency of methylation in breast cancers increased with
      tumor stage and size. In summary, aberrant methylation of the 1A promoter of the
      APC gene and loss of its specific transcript is frequently present in breast and
      NSCLC cancers and cell lines and, to a lesser extent, in SCLC cell lines. Our
      findings may be of biological and clinical importance.

PMID- 11448918
TI  - Circulating hepatitis B virus nucleic acids in chronic infection : representation
      of differently polyadenylated viral transcripts during progression to
      nonreplicative stages.
AB  - PURPOSE: Beside the established maturation of hepatitis B virus (HBV) transcripts
      at a polyadenylation signal downstream of the HBV x protein open reading frame,
      maturation at an internal polyadenylation signal has been observed in the
      chronically infected liver. In the present study, it was the aim to identify the
      respective circulating full-length and truncated transcripts in plasma/serum of
      carriers. EXPERIMENTAL DESIGN: Nucleic acids extracted from sera were analyzed
      using established PCR and reverse transcription-PCR procedures targeted to HBV x
      protein gene regions. Amplification products were cloned and sequenced. RESULTS:
      Base substitution patterns were determined, which indicated infection stages
      advanced to different degrees regardless of the transcript type analyzed. HBV
      full-length RNA (fRNA) showed a high correlation with hepatitis B e antigen and
      viral DNA, indicative for a replicative infection. In contrast, truncated RNA
      (trRNA) appeared to be independent of hepatitis B e antigen and showed only a
      weak association with circulating viral DNA. No correlation was observed between
      the levels of trRNA and the apparent liver damage as reflected by alanine
      transaminase levels. An age-dependent representation of fRNA and trRNA was
      observed: fRNA decreased progressively to low levels, whereas trRNA remained at
      comparably high values. trRNA and RNA not polyadenylated at either of the two
      polyadenylation signals were detected even in the absence of any other
      conventional HBV seromarker, including viral DNA. This was shown for patients
      with cryptogenic cirrhosis and hepatitis C virus carriers. CONCLUSIONS: The
      identification of HBV RNA in human serum has a diagnostic potential for apparent
      and for inapparent infection stages.

PMID- 11448919
TI  - Preclinical pharmacology of BMS-275183, an orally active taxane.
AB  - BMS-275183 is a taxane, the mechanism of action of which is like other known
      taxanes, and is the polymerization of tubulin. BMS-275183 given p.o. was as
      effective as i.v. paclitaxel in five tumor models [murine M109 lung and C3H
      mammary 16/C, and human A2780 ovarian (grown in mice and rats) and HCT/pk colon].
      It was active in one other tumor model (human HCT-116 colon) but inferior to
      parenteral paclitaxel. BMS-275183 given p.o. was active in a human, hormone
      dependent, prostate tumor model, CWR-22, and just as effective as anti-androgen
      chemotherapy. In a schedule dependency study, increasing the interval of time
      between oral administrations resulted in greater cumulative dose tolerance and
      improved therapeutic outcome. Oral BMS-275183 was evaluated as a combination
      therapy in conjunction with i.v. paclitaxel. Therapeutic advantages were evident
      for tumor-bearing mice that received the oral taxane either after induction
      chemotherapy or between courses of such treatment. BMS-275183 is currently in
      Phase I clinical trials at multiple sites.

PMID- 11448920
TI  - Controlled ribozyme targeting demonstrates an antiapoptotic effect of
      carcinoembryonic antigen in HT29 colon cancer cells.
AB  - PURPOSE: Clinical studies suggest that carcinoembryonic antigen (CEA) is
      associated with metastatic progression of colon cancer. However, the biological
      function of CEA is not well understood. We have established an approach that
      allows studying of CEA function within the intact pathophysiological context of
      human colon cancer cells. EXPERIMENTAL DESIGN: We expressed CEA-targeted
      ribozymes under control of a tet-off promoter system in human HT29 colon cancer
      cells. This approach allows regulation of CEA levels on the mRNA and protein
      level by 50% and enables screening analysis of CEA-mediated changes of gene
      expression by cDNA microarray analysis. RESULTS: Comprehensive analysis of 273
      genes revealed that CEA affects expression of various groups of cancer-related
      genes, in particular cell cycle and apoptotic genes. Although cell cycle gene
      expression showed a balanced bidirectional dysregulation, apoptotic genes were
      unidirectionally down-regulated by CEA. In parallel phenotypic studies, CEA did
      not affect cell cycle or proliferation rate. However, CEA significantly protected
      HT29 cells from undergoing apoptosis under various conditions, including
      confluent growth, UV light, IFN-gamma treatment, and treatment with 5
      fluorouracil. CONCLUSIONS: Our study suggests that CEA has an important
      regulatory role in apoptosis, and we propose that CEA is a survival factor for
      colon cancer cells.

PMID- 11448921
TI  - In vitro and in vivo antitumor effect of the anti-CD26 monoclonal antibody 1F7 on
      human CD30+ anaplastic large cell T-cell lymphoma Karpas 299.
AB  - CD26 is a M(r) 110,000 surface glycoprotein with diverse functional properties,
      including having a potentially significant role in tumor development, and
      antibodies to CD26 mediate pleomorphic cellular functions. In this report, we
      show that binding of soluble anti-CD26 monoclonal Ab 1F7 inhibits the growth of
      the human CD30+ anaplastic large cell T-cell lymphoma cell line Karpas 299 in
      both in vitro and in vivo experiments. In vitro experiments show that 1F7 induces
      cell cycle arrest at the G1-S checkpoint, associated with enhanced p21 expression
      that is dependent on de novo protein synthesis. Furthermore, experiments with a
      severe combined immunodeficient mouse tumor model demonstrate that 1F7 treatment
      significantly enhances survival of tumor-bearing mice by inhibiting tumor
      formation. Our data therefore suggest that anti-CD26 treatment may have potential
      clinical use for CD26+ hematological malignancies.

PMID- 11448922
TI  - Three percent dietary fish oil concentrate increased efficacy of doxorubicin
      against MDA-MB 231 breast cancer xenografts.
AB  - Omega 3 polyunsaturated fatty acids (the type of fat found in fish oil) have been
      used to kill or slow the growth of cancer cells in culture and in animal models
      and to increase the effectiveness of cancer chemotherapeutic drugs. An AIN-76
      diet containing 5% corn oil (CO) was modified to contain 3% w/w fish oil
      concentrate (FOC) and 2% CO to test whether a clinically applicable amount of FOC
      is beneficial during doxorubicin (DOX) treatment of cancer xenografts in mice.
      Compared with the diet containing 5% CO, consumption of FOC increased omega 3
      polyunsaturated fatty acids and lipid peroxidation in tumor and liver,
      significantly decreased the ratio of glutathione peroxidase activity to
      superoxide dismutase activity (a putative indicator of increased oxidative
      stress) in tumor but not in the liver, and significantly decreased the tumor
      growth rate. The decreased glutathione peroxidase:superoxide dismutase ratio,
      indicating an altered redox state, in the tumor of FOC-fed mice was significantly
      correlated with decreased tumor-growth rate. Assay of the body weight change,
      blood cell counts, and number of micronuclei in peripheral erythrocytes indicated
      that the toxicity of DOX to the host mouse was not increased in mice fed FOC.
      Thus, a small amount of FOC increased the effectiveness of DOX but did not
      increase the toxicity of DOX to the host mouse. These positive results justify
      clinical testing of FOC in conjunction with cancer chemotherapy.

PMID- 11448923
TI  - Treatment of meningeal breast cancer xenografts in the rat using an anti
      p185/HER2 antibody.
AB  - The metastatic spread of breast cancer to the leptomeninges (LM) is a painful,
      debilitating, and usually lethal condition. Current therapies are generally
      ineffective or extremely toxic. The current study evaluated monoclonal antibody
      therapy in an animal model of LM human breast cancer. Monoclonal antibody 4D5,
      which recognizes the extracellular domain of the HER2/neu receptor, was
      administered into the cerebrospinal fluid of athymic rats implanted with human
      breast cancer cell lines. Continuous intraventricular administration of 4D5
      inhibited growth of SKBR3 cells that overexpress HER2/neu but not of MCF7 cells,
      which do not. Inhibition was dose-dependent, with higher doses of 4D5 producing
      an improved response. i.p. administration of cisplatin in addition to 4D5 did not
      improve results. Continuous administration of 4D5 into the lumbar, as opposed to
      the ventricular intrathecal space, was not therapeutically effective. Treatment
      with 4D5 did not result in outgrowth of cells lacking expression of the HER2/neu
      receptor. These results suggest that 4D5, administered regionally, may palliate
      LM metastases from HER2/neu-overexpressing breast carcinoma.

PMID- 11448924
TI  - Adenovirus-mediated soluble FLT-1 gene therapy for ovarian carcinoma.
AB  - PURPOSE: We hypothesized that adenovirus-mediated soluble fms-like tyrosine
      kinase receptor (sFLT-1) gene therapy can inhibit the ovarian tumor growth and
      increase survival of mice in the context of ovarian carcinoma. EXPERIMENTAL
      DESIGN: We constructed an infectivity-enhanced recombinant adenovirus
      (AdRGDGFPsFLT-1) expressing soluble FLT-1 and green fluorescent protein (GFP). An
      adenovirus AdRGDGFP expressing GFP alone was used as control. The functional
      validation of adenovirus-mediated sFLT-1 was determined by an in vitro human
      umbilical vein endothelial cell proliferation inhibition assay. To evaluate the
      therapeutic potential of adenovirus-expressed sFLT-1 to inhibit the growth of
      ovarian tumors and to increase the survival duration of mice with ovarian tumors,
      two tumor models were used. First, SKOV3.ip1 ovarian carcinoma cells were
      infected ex vivo with either AdRGDGFPsFLT-1 or AdRGDGFP or uninfected and then
      inoculated s.c. into BALB/c nude mice, and tumor growth was monitored. Second,
      SKOV3.ip1 cells were inoculated i.p. into CB17 SCID mice and then treated with
      two doses of either AdRGDGFPsFLT-1 or AdRGDGFP or with PBS on days 1 and 14 after
      inoculation of cells, and the survival duration was monitored. RESULTS: Treatment
      with adenovirus-expressed sFLT-1 significantly inhibited the proliferation of
      human umbilical vein endothelial cells. The s.c. tumor nodules in mice derived
      from cells infected with AdRGDGFPsFLT-1 were significantly smaller than those
      infected with either AdRGDGFP or uninfected. In addition, i.p. administration of
      the AdRGDGFPsFLT-1 resulted in a significant increase in the survival times of
      mice compared with AdRGDGFP- or PBS-treated mice. CONCLUSIONS: Our results
      suggest that adenovirus-mediated sFLT-1 gene therapy can effectively inhibit
      ovarian tumor growth and increase survival in a murine model of ovarian
      carcinoma.

PMID- 11448925
TI  - Cerivastatin triggers tumor-specific apoptosis with higher efficacy than
      lovastatin.
AB  - The statin family of drugs inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)
      reductase, the rate-limiting enzyme of the mevalonate pathway, and is used
      clinically as a safe and effective approach in the control of
      hypercholesterolemia. We have shown previously (Dimitroulakos, J., Nohynek, D.,
      Backway, K. L., Hedley, D. W., Yeger, H., Freedman, M. H., Minden, M D., and
      Penn, L. Z. Increased sensitivity of acute myelogenous leukemias to lovastatin
      induced apoptosis: a potential therapeutic approach. Blood, 93: 1308-1318, 1999)
      that lovastatin, a prototypic member of the statin family, can induce apoptosis
      of human acute myeloid leukemia (AML) cells in a sensitive and specific manner.
      In the present study, we evaluated the relative potency and mechanism of action
      of the newer synthetic statins, fluvastatin, atorvastatin, and cerivastatin, to
      trigger tumor-specific apoptosis. Cerivastatin is at least 10 times more potent
      than the other statins at inducing apoptosis in AML cell lines. Cerivastatin
      induced apoptosis is reversible with the addition of the immediate product of the
      HMG-CoA reductase reaction, mevalonate, or with a distal product of the pathway,
      geranylgeranyl pyrophosphate. This suggests protein geranylgeranylation is an
      essential downstream component of the mevalonate pathway for cerivastatin similar
      to lovastatin-induced apoptosis. The enhanced potency of cerivastatin expands the
      number of AML patient samples as well as the types of malignancies, which respond
      to statin-induced apoptosis with acute sensitivity. Cells derived from acute
      lymphocytic leukemia are only weakly sensitive to lovastatin cytotoxicity but
      show robust response to cerivastatin. Importantly, cerivastatin is not cytotoxic
      to nontransformed human bone marrow progenitors. These results strongly support
      the further testing of cerivastatin as a novel anticancer therapeutic alone and
      in combination with other agents in vivo.

PMID- 11448926
TI  - Destabilization of steroid receptors by heat shock protein 90-binding drugs: a
      ligand-independent approach to hormonal therapy of breast cancer.
AB  - Steroid hormone receptors have become an important target in the management of
      breast cancers. Despite a good initial response rate, however, most tumors become
      refractory to current hormonal therapies within a year of starting treatment. To
      address this problem, we evaluated the effects of agents that bind the molecular
      chaperone heat shock protein 90 (Hsp90) on estrogen receptor function in breast
      cancer. Unstimulated estrogen and progesterone receptors exist as multimolecular
      complexes consisting of the hormone-binding protein itself and several essential
      molecular chaperones including Hsp90. We found that interaction of the Hsp90
      binding drugs geldanamycin and radicicol with the chaperone destabilizes these
      hormone receptors in a ligand-independent manner, leading to profound and
      prolonged depletion of their levels in breast cancer cells cultured in vitro.
      Consistent with these findings, in vivo administration of the geldanamycin
      derivative 17-allylaminogeldanamycin (17AAG; NSC330507) to estrogen-supplemented,
      tumor-bearing SCID mice resulted in marked depletion of progesterone receptor
      levels in both uterus and tumor. Drug administration also delayed the growth of
      established, hormone-responsive MCF-7 and T47D human tumor xenografts for up to 3
      weeks after the initiation of therapy. We conclude that in light of their novel
      mechanism of anti-hormone action, consideration should be given to examining the
      activity of 17AAG and other Hsp90-binding agents in patients with refractory
      breast cancer in future clinical trials, either alone or in combination with
      conventional hormone antagonists.

PMID- 11448927
TI  - Kinetics of neutrophil production in normal and neutropenic animals during the
      response to filgrastim (r-metHu G-CSF) or filgrastim SD/01 (PEG-r-metHu G-CSF).
AB  - Filgrastim G-CSF has a short, biologically active half-life, and its effective
      use depends on repeated inoculations. A major aim, therefore, has been to develop
      a once-per-chemotherapy cycle formulation. To this end, a polyethylene
      glycolylated form of Filgrastim, known as SD/01, has been developed. In this
      study, we compared the cellular kinetics of granulocyte production in mice
      stimulated with SD/01 and granulocyte colony-stimulating factor (G-CSF). Mice
      were injected with a single dose of SD/01 (1 mg/kg) or G-CSF (125 microg/kg)
      twice per day for 4 days. Mice rendered leukopenic with a single injection of
      cyclophosphamide (200 mg/kg) and temozolomide (90 mg/kg) were similarly treated
      at their 3-day neutrophil nadir. Tritiated thymidine was injected for
      autoradiographic labeling studies. Bone marrow labeling indices and the release
      of labeled neutrophils and monocytes into the peripheral blood were assessed.
      Granulocytopoiesis was stimulated similarly by both SD/01 and G-CSF in both
      normal and neutropenic animals, with counts rising to >20 x 10(9)
      polymorphonuclear neutrophils/l in both cases. Bone marrow thymidine labeling
      indices were increased, indicating a greater proportion of cells in DNA synthesis
      and an elevated proliferative activity. Compared with the normally slow release
      of neutrophils into the peripheral blood, labeled neutrophils (and monocytes)
      were rapidly released, increasing to peak levels at approximately 24 h. The
      peripheral half-life of neutrophils was not significantly different from normal,
      and the mitotic amplification factors for increase in granulocytopoiesis,
      accounted for by 3-3.9 extra cell divisions, were comparable for both factors. We
      conclude that neutrophil kinetics are stimulated in the same way and to the same
      extent by both SD/01 and G-CSF.

PMID- 11448928
TI  - The olivacine S16020 enhances the antitumor effect of ionizing radiation without
      increasing radio-induced mucositis.
AB  - The combination of a novel topoisomerase II inhibitor, S16020, and ionizing
      radiation (IR) was investigated with the aim of assessing normal tissue tolerance
      using a mouse mucosal lip model and antitumor activity in a human carcinoma
      (HEP2) cell line. No increase of acute mucosal reactions was seen when combining
      S16020 with IR as compared with IR alone. Using clonogenic cell survival assay, a
      marked enhancement of HEP2 cell killing was found when S16020 was combined with
      irradiation. Additional in vivo combination of S16020-IR was able to increase
      markedly the antitumor efficacy as compared with S16020 or irradiation alone.
      Interestingly, the radiosensitization effect in vivo was observed at relatively
      low and nontoxic concentrations of S16020, and no dose-effect relationship was
      found beyond 30 mg/kg. In conclusion, the combination of IR and S16020 seems
      promising to enhance antitumor activity without increasing deleterious effect in
      normal tissues and to provide the basis for a new radio-chemotherapy combination.

PMID- 11448929
TI  - Preventive effect of FK143, a 5alpha-reductase inhibitor, on chemical
      hepatocarcinogenesis in rats.
AB  - The incidence of hepatocellular carcinoma (HCC) is more prevalent in males than
      in females. 5alpha-Dihydrotestosterone is the most potent form of androgen and is
      converted from testosterone by 5alpha-reductase. The antitumor effect of a 5alpha
      reductase inhibitor (FK143) was evaluated in a rat chemical hepatocarcinogenesis
      model (Solt-Farber). Male Fischer 344 rats were used in three groups: (a) control
      group; (b) low-dose FK143 (FKL) group (20 ppm FK143); and (c) high-dose FK143
      (FKH) group (200 ppm FK143). The numbers of both glutathione S-transferase
      placental form-positive foci (P < 0.05) and hyperplastic nodules (HNs; P < 0.01)
      in the liver were significantly lower in the FKL group than in the control group.
      The numbers (P < 0.05) and tumor volume (P < 0.01) of HCCs per liver were
      significantly lower in the FKL group when compared with the control group. All
      HCCs were well differentiated in the FKL group, whereas 38% and 36% of HCCs were
      moderate to poorly differentiated in the control group and the FKH group,
      respectively. The proliferating cell nuclear antigen labeling index:apoptotic
      index ratios of enzyme-altered foci, HNs, and HCCs were significantly lower in
      the FKL group than in the control group. Serum 5alpha-dihydrotestosterone was
      significantly lower in both the FKL and FKH groups. However, a high dose of FK143
      (200 ppm) provided no protection against hepatocarcinogenesis, and the level of
      serum testosterone was elevated in this group when compared with that in the
      control group. The low dose of FK143 significantly suppressed the formation of
      enzyme-altered foci, HNs, and HCCs in rat hepatocarcinogenesis. This may indicate
      that 5alpha-dihydrotestosterone enhances hepatocarcinogenesis. We conclude that
      an optimal dose of FK143 may have a suppressive effect on hepatocarcinogenesis.

PMID- 11448930
TI  - In vitro and in vivo properties of novel nucleoside transport inhibitors with
      improved pharmacological properties that potentiate antifolate activity.
AB  - The activity of antimetabolite inhibitors of de novo deoxyribonucleotide
      biosynthesis can be compromised by the salvage of extracellular preformed
      nucleosides and nucleobases. Dipyridamole (DP) is a nucleoside transport
      inhibitor that has been used clinically in an attempt to increase antimetabolite
      activity; however, DP binds tightly to the serum protein alpha1-acid glycoprotein
      (AGP) thereby rendering this therapeutic strategy largely ineffective. Four novel
      DP analogues (NU3076, NU3084, NU3108, and NU3121) have been developed with
      substitutions at the 2,6- and 4,8-positions of the pyrimidopyrimidine ring. The
      novel DP analogues inhibit thymidine (dThd) uptake into L1210 cells in vitro
      (NU3076 IC(50), 0.25 microM; NU3084 IC(50), 0.27 microM; NU3108 IC(50), 0.31
      microM; NU3121 IC(50), 0.26 microM; and DP IC(50), 0.37 microM), but, unlike DP,
      their activity remains largely unaffected in the presence of 5 mg/ml AGP. The
      four DP analogues inhibit dThd and hypoxanthine rescue from Alimta (multitargeted
      antifolate)-induced growth inhibition in A549 and COR L23 human lung carcinoma
      cell lines in the presence of 2.5 mg/ml AGP, whereas the activity of DP is
      completely abolished. i.p. administration of 10 mg/kg NU3108, NU3121, and DP
      produced peak plasma concentrations of 4.4, 2.1, and 6.7 microM, respectively,
      and levels were sustained above 1 microM for approximately 45 min (DP) and 120
      min (NU3108 and NU3121). [3H]thymidine incorporation into COR L23 xenografts
      grown in CD1 nude mice was reduced by 64% (NU3108), 44% (NU3121), and 65% (DP) 2
      h after administration of the nucleoside transport inhibitors. In conclusion, two
      novel DP analogues (NU3108 and NU3121) have been identified that do not bind to
      AGP and that display superior pharmacokinetic profiles in comparison to DP and
      inhibit [3H]thymidine incorporation into human tumor xenografts in vivo.

PMID- 11448931
TI  - The impact of p53 status on cellular sensitivity to antifolate drugs.
AB  - The impact of p53 status on cellular sensitivity to antifolate drugs has been
      examined in seven human cell lines (A549, MCF7, T-47D, CCRF-CEM, COR-L23, A2780,
      and HCT-116) and p53 nonfunctional counterparts of two of the cell lines (HCT
      116/N7 and A2780/CP70). p53 status was determined by sequencing and functional
      assays. The sensitivities of the cell lines to growth inhibition (sulphorhodamine
      B assay) produced by four antifolate drugs (Alimta, methotrexate, raltitrexed,
      and lometrexol) were studied. There was no clear relationship between functional
      p53 status and sensitivity to methotrexate or lometrexol, whereas a functional
      p53 status was possibly associated with resistance to Alimta- and raltitrexed
      induced growth inhibition. In contrast, in the two pairs of related human tumor
      cell lines (HCT-116 and HCT-116/N7 and A2780 and A2780/CP70) cells with
      functional p53 were more sensitive to Alimta- and raltitrexed-induced growth
      inhibition (P = 0.002). Detailed studies were performed with the A2780 cell
      lines, and in the parental cells sensitivity to Alimta- and raltitrexed-induced
      cytotoxicity (clonogenic assay) was similar to the sensitivity determined in the
      sulphorhodamine B assay. However, in A2780/CP70 cells, 1 microM of drug resulted
      in only 40-60% growth inhibition yet > or = 85% cytotoxicity. After Alimta and
      raltitrexed exposure for < or = 72 h, there were no differences between the A2780
      and A278/CP70 cell lines in cell cycle phase distribution, absolute cell number,
      or the induction of apoptosis. However, the cellular protein content of the
      A2780/CP70 cells was 3-6-fold higher than in A2780 cells after Alimta and
      raltitrexed treatment, suggesting that cells without functional p53 can maintain
      protein synthesis in the absence of cell division (unbalanced cell growth). In
      conclusion, the apparent impact of functional p53 status on sensitivity to
      antifolate drugs may depend upon the phenotypic/genotypic background as well as
      the assay used to measure cellular sensitivity.

PMID- 11448932
TI  - In vivo antitumor activity of bis(4,7-dimethyl-1,10-phenanthroline)
      sulfatooxovanadium(IV) (METVAN [VO(SO4)(Me2-Phen)2]).
AB  - The compound bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (METVAN
      [VO(SO4)(Me2-Phen)2]), exhibits potent cytotoxicity against human cancer cells at
      low micromolar concentrations. At concentrations > or = 1 microM, METVAN
      treatment was associated with a nearly complete loss of the adhesive, migratory,
      and invasive properties of the treated tumor cell populations. METVAN did not
      cause acute or subacute toxicity in mice at dose levels ranging from 12.5 mg/kg
      to 100 mg/kg. Therapeutic plasma concentrations > or = 5 microM were rapidly
      achieved and maintained in mice for at least 24 h after i.p. bolus injection of a
      single 10 mg/kg nontoxic dose of METVAN. At this dose level, the maximum plasma
      METVAN concentration was 37.0 microM, which was achieved with a t(max) of 21.4
      min. Plasma samples (diluted 1:16) from METVAN-treated mice killed 85% of human
      breast cancer cells in vitro. METVAN was slowly eliminated with an apparent
      plasma t(1/2) of 17.5 h and systemic clearance of 42.1 ml/h/kg. In accordance
      with its potent in vitro activity and favorable in vivo pharmacokinetics, METVAN
      exhibited significant antitumor activity and delayed tumor progression in CB.17
      severe combined immunodeficient (SCID) mouse xenograft models of human
      glioblastoma and breast cancer. In these experiments, METVAN was administered in
      daily injections of a single nontoxic 10 mg/kg i.p. dose on 5 consecutive days
      per week for 4 consecutive weeks beginning the day after the s.c. inoculation of
      U87 glioblastoma or MDA-MB-231 breast cancer cells. At 40 days after the
      inoculation of tumor cells, the U87 tumor xenografts in the vehicle-treated
      control SCID mice were much larger than those of the mice treated with METVAN
      (4560 +/- 654 mm(3) versus 1688 +/- 571 mm(3); P = 0.003). Similarly, the MDA-MB
      231 tumors in SCID mice treated with METVAN were much smaller 40 days after tumor
      cell inoculation than those of the vehicle-treated control SCID mice (174 +/- 29
      mm(3) versus 487 +/- 82 mm(3); P = 0.002). The favorable in vivo pharmacodynamic
      features and antitumor activity of METVAN warrants further development of this
      novel oxovanadium compound as a potential new anticancer agent.

PMID- 11448933
TI  - Intracellular association of a mutant insulin-like growth factor receptor with
      endogenous receptors.
AB  - The type 1 insulin-like growth factor receptor (IGF-IR) is emerging as a powerful
      survival factor against a variety of apoptotic agents in many cell types. A
      mutant IGF-IR designated 486/STOP is known to induce apoptosis and inhibit the
      growth of human tumor cells in mice. We have investigated the mechanism of action
      of 486/STOP. To study it, we have developed a new retroviral vector in which we
      have combined a self-inactivating 5'-long terminal repeat with an inducible heat
      shock promoter (heat shock protein 70) from Drosophila. Using this technique, we
      find that the polypeptide encoded by 486/STOP is partially retained within the
      cell and partially secreted. However, the secreted polypeptide is subsequently
      taken up by the cells. In both cases, a specific intracellular interaction of
      486/STOP with the endogenous IGF-IRs can be demonstrated by
      coimmunoprecipitation.

PMID- 11448934
TI  - High expression of the Cap43 gene in infiltrating macrophages of human renal cell
      carcinomas.
AB  - We used suppression subtractive hybridization to identify highly expressed genes
      in the cancerous region of human renal cell carcinoma (RCC) compared with
      noncancerous tissue. Nine genes were identified to show increased expression in
      the cancerous region compared with the noncancerous region. The nine genes
      included thymosin beta4, secreted protein acidic and rich in cysteine (SPARC),
      Cap43, ceruloplasmin, serum amyloid A, osteopontin, heat shock protein 90
      (HSP90), LOT1, and casein kinase I. Of these 9 genes, in situ hybridization with
      10 clinical samples consistently showed a strong expression of Cap43 mRNA in
      infiltrating macrophages in RCCs, but not in cancer cells proliferating in an
      alveolar pattern. However, Cap43 mRNA was also apparently detected in epithelial
      cells of the renal proximal tubuli in noncancerous tissue. The higher expression
      of the Cap43 gene in the cancerous region of RCCs appears to depend on macrophage
      infiltration. Moreover, treatment with phorbol ester resulted in enhanced
      expression of the Cap43 gene in human monocytic cells in vitro. The expression of
      the Cap43 gene in infiltrating macrophages is discussed in association with the
      differentiated or activated status of monocyte/macrophage.

PMID- 11448935
TI  - SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded
      polyglutamine in TATA-binding protein.
AB  - Genetic etiologies of at least 20% of autosomal dominant cerebellar ataxias
      (ADCAs) have yet to be clarified. We identified a novel spinocerebellar ataxia
      (SCA) form in four Japanese pedigrees which is caused by an abnormal CAG
      expansion in the TATA-binding protein (TBP) gene, a general transcription
      initiation factor. Consequently, it has been added to the group of polyglutamine
      diseases. This abnormal expansion of glutamine tracts in TBP bears 47--55
      repeats, whereas the normal repeat number ranges from 29 to 42.
      Immunocytochemical examination of a postmortem brain which carried 48 CAG repeats
      detected neuronal intranuclear inclusion bodies that stained with anti-ubiquitin
      antibody, anti-TBP antibody and with the 1C2 antibody that recognizes
      specifically expanded pathological polyglutamine tracts. We therefore propose
      that this new disease be called SCA17 (TBP disease).

PMID- 11448936
TI  - Reduced FMRP and increased FMR1 transcription is proportionally associated with
      CGG repeat number in intermediate-length and premutation carriers.
AB  - The 5' untranslated CGG repeat in the fragile X mental retardation-1 (FMR1) gene
      is expanded in families with fragile X syndrome, with more than 200 CGGs
      resulting in mental retardation due to the absence of the encoded fragile X
      mental retardation protein (FMRP). Intermediate and premutation alleles,
      containing between approximately 40 and 200 repeats, express grossly normal FMRP
      levels and such carriers are widely believed to be non-penetrant, despite
      continued reports of subtle cognitive/psychosocial impairment and other
      phenotypes. Using a highly sensitive quantification assay, we demonstrate
      significantly diminished FMRP levels in carriers, negatively correlated with
      repeat number. Despite reduced FMRP, these carrier alleles overexpress FMR1,
      resulting in a positive correlation between repeat number and FMR1 message level.
      These biochemical deviations associated with intermediate and premutation FMR1
      alleles, found in approximately 4% of the population, suggest that the phenotypic
      spectrum of fragile X syndrome may need to be revisited.

PMID- 11448937
TI  - An element in intron 1 of the CFTR gene augments intestinal expression in vivo.
AB  - The elements controlling the complex developmental and tissue-specific expression
      of the cystic fibrosis transmembrane conductance regulator (CFTR) gene lie
      outside the basal promoter region and have not been characterized. We previously
      identified a tissue-specific DNase I hypersensitive site (DHS) in intron 1 (185 +
      10 kb) of the CFTR gene. Here we show that removal of the core element abolishes
      the activity of this DHS in transient transfection assays of reporter/enhancer
      gene constructs. We then compared expression from a 310 kb yeast artificial
      chromosome (YAC) that contains the entire CFTR gene with expression from the same
      YAC from which the DHS element had been deleted. Stable transfection of a human
      colon carcinoma cell line showed that transcription from the deleted YAC was
      reduced by approximately 60%. In transgenic mice, deletion of the intron 1 DHS
      had no effect on expression in the lung, but reduced expression in the intestine
      by approximately 60%. Thus, the regulatory element associated with the intron 1
      DHS is tissue-specific and is required for normal CFTR expression levels in the
      intestinal epithelium in vivo.

PMID- 11448938
TI  - Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the
      paraventricular nucleus of the hypothalamus.
AB  - The bHLH-PAS transcription factor SIM1 is required for the development of the
      paraventricular nucleus (PVN) of the hypothalamus. Mice homozygous for a null
      allele of Sim1 (Sim1(-/-)) lack a PVN and die perinatally. In contrast, we show
      here that Sim1 heterozygous mice are viable but develop early-onset obesity, with
      increased linear growth, hyperinsulinemia and hyperleptinemia. Sim1(+/-) mice are
      hyperphagic but their energy expenditure is not decreased, distinguishing them
      from other mouse models of early-onset obesity such as deficiencies in leptin and
      melanocortin receptor 4. Quantitative histological comparison with normal
      littermates showed that the PVN of Sim1(+/-) mice contains on average 24% fewer
      cells without a selective loss of any identifiable major cell type. Since
      acquired lesions in the PVN also induce increased appetite without a decrease in
      energy expenditure, we propose that abnormalities of PVN development cause the
      obesity of Sim1(+/-) mice. Severe obesity was described recently in a patient
      with a balanced translocation disrupting SIM1. Pathways controlling the
      development of the PVN thus have the potential to cause obesity in both mice and
      humans.

PMID- 11448939
TI  - A conserved imprinting control region at the HYMAI/ZAC domain is implicated in
      transient neonatal diabetes mellitus.
AB  - Transient neonatal diabetes mellitus (TNDM) is associated with intra-uterine
      growth retardation, dehydration and a lack of insulin. Some TNDM patients exhibit
      paternal uniparental disomy (UPD) of chromosome 6q24, where at least two
      imprinted genes, HYMAI and ZAC, have so far been characterized. Here we show that
      the differentially methylated CpG island that partially overlaps mZac1 and mHymai
      at the syntenic mouse locus is a likely imprinting control region (ICR) for the
      approximately 120--200 kb domain. The region is unmethylated in sperm but
      probably methylated in oocytes, a difference that persists between parental
      alleles throughout pre- and post-implantation development. We also show that
      within this ICR, there is a region that exhibits a high degree of homology
      between mouse and human. Using a reporter expression assay, we demonstrate that
      this conserved region acts as a strong transcriptional repressor when methylated.
      Finally, we provide in vivo evidence that in the majority of TNDM patients with a
      normal karyotype, there is a loss of methylation within the highly homologous
      region. We propose that this ICR regulates expression of imprinted genes within
      the domain; epigenetic or genetic mutations of this region probably result in
      TNDM, possibly by affecting expression of ZAC in the pancreas and/or the
      pituitary.

PMID- 11448940
TI  - Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene:
      correlation between sulfate transport activity and chondrodysplasia phenotype.
AB  - The diastrophic dysplasia sulfate transporter (DTDST) gene encodes a
      transmembrane protein that transports sulfate into chondrocytes to maintain
      adequate sulfation of proteoglycans. Mutations in this gene are responsible for
      four recessively inherited chondrodysplasias that include diastrophic dysplasia,
      multiple epiphyseal dysplasia, atelosteogenesis type 2 and achondrogenesis 1B
      (ACG-1B). To determine whether the DTDST mutations found in individuals with
      these chondrodysplasias differ functionally from each other, we compared the
      sulfate transport activity of 11 reported DTDST mutations. Five mutations, G255E,
      Delta a1751, L483P, R178X and N425D, had minimal sulfate transport function
      following expression in Xenopus laevis oocytes. Two mutations, Delta V340 and
      R279W, transported sulfate at rates of 17 and 32%, respectively, of wild-type
      DTDST. Four mutations, A715V, C653S, Q454P and G678V, had rates of sulfate
      transport nearly equal to that of wild-type DTDST. Transport kinetics were not
      different among the four mutations with near-normal sulfate transport function
      and wild-type DTDST. When the sulfate transport function of the different DTDST
      mutations are grouped according to the general phenotypes, individuals with the
      most severe form, ACG-1B, tend to be homozygous for null mutations, individuals
      with the moderately severe atelosteogenesis type 2 have at least one allele with
      a loss-of-function mutation, and individuals with the mildest forms are typically
      homozygous for mutations with residual sulfate transport function. However, in
      the X.laevis oocyte expression system, the correlation between residual transport
      function and the severity of phenotype was not absolute, suggesting that factors
      in addition to the intrinsic sulfate transport properties of the DTDST protein
      may influence the phenotype in individuals with DTDST mutations.

PMID- 11448941
TI  - Positive associations between single nucleotide polymorphisms in the IGF2 gene
      region and body mass index in adult males.
AB  - We previously demonstrated an association between the insulin-like growth factor
      2 (IGF2) gene 3'-untranslated region (3'-UTR) ApaI polymorphism and body mass
      index (BMI) in over 2500 middle-aged Caucasoid males. In the same cohort, we have
      now tested association with 11 more markers, including seven novel single
      nucleotide polymorphisms (SNPs), spanning >30 kb across the IGF2 gene. Three SNPs
      showed significant positive associations with BMI: 6815 A/T in the IGF2 P1
      promoter (P = 0.00012, n = 2394) and the newly identified SNPs 1156 C/T in intron
      2 (P = 0.017, n = 1567) and 1926 C/G in the 3'-UTR (P = 0.0062, n = 1872). There
      was strong pairwise linkage disequilibrium (LD) between the ApaI and 1926 C/G
      sites, whereas LD between ApaI and 6815 A/T, and between ApaI and 1156 T/C, was
      minimal. Univariately 6815 A/T, 1156 T/C and ApaI explained 1.03, 1.02 and 0.67%
      of the variation in BMI. Multi-way analysis of variance (ANOVA) models showed
      that 6815 A/T and 1156 T/C explained a further 0.4 and 0.8% of the variation
      beyond that accounted for by ApaI and the association of 1926 C/G with BMI
      disappeared after adjustment. The 6815 A/T, 1156 T/C and ApaI markers in effect
      constitute independent affirmations of our original hypothesized candidate gene
      region. In a stepwise multi-way ANOVA model, all three terms were significantly
      independently associated with BMI. The total proportion of BMI variance explained
      by this model was 2.25%, strongly suggesting that IGF2 genetic variation is a
      significant determinant of body weight in middle-aged males.

PMID- 11448942
TI  - Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a
      syndromic Hirschsprung disease.
AB  - Hirschsprung disease (HD) has been described in association with microcephaly,
      mental retardation and characteristic facial features, delineating a syndrome
      possibly caused by mutations localized at chromosome 2q22--q23. We have analyzed
      a de novo translocation breakpoint at 2q22 in one patient presenting with this
      syndrome, and identified a gene, SIP1, which is disrupted by this chromosomal
      rearrangement. SIP1 encodes Smad interacting protein 1, a new member of the delta
      EF1/Zfh-1 family of two-handed zinc finger/homeodomain transcription factors. We
      determined the genomic structure and expression of the human SIP1 gene. Further
      analysis of four independent patients showed that SIP1 is altered by heterozygous
      frameshift mutations causing early truncation of the protein. SIP1, among other
      functions, seems to play crucial roles in normal embryonic development of neural
      structures and neural crest. Its deficiency, in altering function of the TGF
      beta/BMP/Smad-mediated signalling cascade, is consistent with some of the
      dysmorphic features observed in this syndrome, in particular the enteric nervous
      system defect that underlies HD.

PMID- 11448943
TI  - Over-expression of inducible HSP70 chaperone suppresses neuropathology and
      improves motor function in SCA1 mice.
AB  - Many neurodegenerative diseases are caused by gain-of-function mechanisms in
      which the disease-causing protein is altered, becomes toxic to the cell, and
      aggregates. Among these 'proteinopathies' are Alzheimer's and Parkinson's
      disease, prion disorders and polyglutamine diseases. Members of this latter
      group, also known as triplet repeat diseases, are caused by the expansion of
      unstable CAG repeats coding for glutamine within the respective proteins.
      Spinocerebellar ataxia type 1 (SCA1) is one such disease, characterized by loss
      of motor coordination due to the degeneration of cerebellar Purkinje cells and
      brain stem neurons. In SCA1 and several other polyglutamine diseases, the
      expanded protein aggregates into nuclear inclusions (NIs). Because these NIs
      accumulate molecular chaperones, ubiquitin and proteasomal subunits--all
      components of the cellular protein re-folding and degradation machinery--we
      hypothesized that protein misfolding and impaired protein clearance might
      underlie the pathogenesis of polyglutamine diseases. Over-expressing specific
      chaperones reduces protein aggregation in transfected cells and suppresses
      neurodegeneration in invertebrate animal models of polyglutamine disorders. To
      determine whether enhancing chaperone activity could mitigate the phenotype in a
      mammalian model, we crossbred SCA1 mice with mice over-expressing a molecular
      chaperone (inducible HSP70 or iHSP70). We found that high levels of HSP70 did
      indeed afford protection against neurodegeneration.

PMID- 11448944
TI  - Functional analysis of neurofibromatosis 2 (NF2) missense mutations.
AB  - Neurofibromatosis 2 (NF2) is a tumor predisposition syndrome in which affected
      individuals develop nervous system tumors at an increased frequency. The most
      common tumor in individuals with NF2 is the schwannoma, which is composed of
      neoplastic Schwann cells lacking NF2 gene expression. Moreover, inactivation of
      the NF2 gene is observed in nearly all sporadic schwannomas, suggesting that the
      NF2 gene is a critical growth regulator for Schwann cells. In an effort to gain
      insights into the function of the NF2 gene product, merlin or schwannomin, we
      performed a detailed functional analysis of eight naturally occurring non
      conservative missense mutations in the NF2 gene. Using a regulatable expression
      system in rat schwannoma cells, we analyzed proliferation, actin cytoskeleton
      mediated events and merlin folding. In this report, we demonstrate that mutations
      clustered in the predicted alpha-helical region did not impair the function of
      merlin whereas those in either the N- or C-terminus of the protein rendered
      merlin inactive as a negative growth regulator. These results suggest that the
      key functional domains of merlin lie within the highly conserved FERM domain and
      the unique C-terminus of the protein.

PMID- 11448945
TI  - Steroid hormone receptor-mediated histone deacetylation and transcription at the
      mouse mammary tumor virus promoter.
AB  - Acetylation of lysines in histones H3 and H4 N-terminal tails is associated with
      transcriptional activation and deacetylation with repression. Our studies with
      the mouse mammary tumor virus (MMTV) promoter in chromatin show significant
      levels of acetylation at promoter proximal and distal regions prior to
      transactivation. Upon activation with glucocorticoids or progestins, promoter
      proximal histones become deacetylated within the region of inducible nuclease
      hypersensitivity. The deacetylation lags behind the initiation of transcription,
      indicating a role in post-activation regulation. Our results indicate a novel
      mechanism by which target promoters are regulated by steroid receptors and
      chromatin modification machinery.

PMID- 11448946
TI  - Transendothelial migration of colon carcinoma cells requires expression of E
      selectin by endothelial cells and activation of stress-activated protein kinase-2
      (SAPK2/p38) in the tumor cells.
AB  - Adhesion and migration of tumor cells on and through the vascular endothelium are
      critical steps of the metastatic invasion. We investigated the roles of E
      selectin and of stress-activated protein kinase-2 (SAPK2/p38) in modulating
      endothelial adhesion and transendothelial migration of HT-29 colon carcinoma
      cells. Tumor necrosis factor alpha (TNF alpha) strongly increased the expression
      of E-selectin in human umbilical vein endothelial cells (HUVEC). This effect was
      independent of the activation of SAPK2/p38 induced by TNF alpha. Adhesion of HT
      29 cells on a monolayer of HUVEC pretreated with TNF alpha was dependent on E
      selectin expression but was independent of SAPK2/p38 activity of both HUVEC and
      tumor cells. The adhesion of HT-29 cells to E-selectin-expressing HUVEC led to
      the activation of SAPK2/p38 in the tumor cells as reflected by the increased
      phosphorylation of the actin-polymerizing factor HSP27 by mitogen-activated
      protein kinase 2/3, a direct target of SAPK2/p38. Moreover, a recombinant E
      selectin/Fc chimera quickly increased the activation of SAPK2/p38 in HT-29 cells.
      Blocking the increased activity of SAPK2/p38 of HT-29 cells by SB203580 or by
      expressing a dominant negative form of SAPK2/p38 inhibited their transendothelial
      migration. Similarly, HeLa cells stably expressing a kinase-inactive mutant of
      SAPK2/p38 showed a decreased capacity to cross a layer of HUVEC. Overall, our
      results suggest that the regulation of transendothelial migration of tumor cells
      involves two essential steps as follows: adhesion to the endothelium through
      adhesion molecules, such as E-selectin, and increased motogenic potential through
      adhesion-mediated activation of the SAPK2/p38 pathway.

PMID- 11448947
TI  - Cross-talk between the p42/p44 MAP kinase and Smad pathways in transforming
      growth factor beta 1-induced furin gene transactivation.
AB  - Furin, a predominant convertase of the cellular constitutive secretory pathway,
      is known to be involved in the maturation of a number of growth/differentiation
      factors, but the mechanisms governing its expression remain elusive. We have
      previously demonstrated that transforming growth factor (TGF) beta 1, through the
      activation of Smad transducers, regulates its own converting enzyme, furin,
      creating a unique activation/regulation loop of potential importance in a variety
      of cell fate and functions. Here we studied the involvement of the p42/p44 MAPK
      pathway in such regulation. Using HepG2 cells transfected with fur P1 LUC
      (luciferase) promoter construct, we observed that forced expression of a dominant
      negative mutant form of the small G protein p21(ras) (RasN17) inhibited TGF beta
      1-induced fur gene transcription, suggesting the involvement of the p42/p44 MAPK
      cascade. In addition, TGF beta induced sustained activation/phosphorylation of
      endogenous p42/p44 MAPK. Further-more, the role of MAPK cascade in fur gene
      transcription was highlighted by the use of the MEK1/2 inhibitors, PD98059 or
      U0126, or co-expression of a p44 antisense construct that repressed the induction
      of fur promoter transactivation. Conversely, overexpression of a constitutively
      active form of MEK1 increased unstimulated, TGF beta 1-stimulated, and Smad2
      stimulated promoter P1 transactivation, and the universal Smad inhibitor, Smad7,
      inhibited this effect. Activation of Smad2 by MEK1 or TGF beta 1 resulted in an
      enhanced nuclear localization of Smad2, which was inhibited upon blocking MEK1
      activity. Our findings clearly show that the activation of the p42/p44 MAPK
      pathway is involved in fur gene expression and led us to propose a co-operative
      model whereby TGF beta 1-induced receptor activation stimulates not only a Smad
      pathway but also a parallel p42/p44 MAPK pathway that targets Smad2 for an
      increased nuclear translocation and enhanced fur gene transactivation. Such an
      uncovered mechanism may be a key determinant for the regulation of furin in
      embryogenesis and growth-related physiopathological conditions.

PMID- 11448948
TI  - Cell transformation by the E5/E8 protein of bovine papillomavirus type 4.
      p27(Kip1), Elevated through increased protein synthesis is sequestered by cyclin
      D1-CDK4 complexes.
AB  - The E5/E8 hydrophobic protein of BPV-4 is, at only 42 residues, the smallest
      transforming protein identified to date. Transformation of NIH-3T3 cells by E5/E8
      correlates with up-regulation of both cyclin A-associated kinase activity and,
      unusually, p27(Kip1) (p27) but does not rely on changes in cyclin E or cyclin E
      CDK2 activity. Here we have examined how p27 is prevented from functioning
      efficiently as a CDK2 inhibitor, and we investigated the mechanisms used to
      achieve elevated p27 expression in E5/E8 cells. Our results show that normal
      subcellular targeting of p27 is not subverted in E5/E8 cells, and p27 retains its
      ability to inhibit both cyclin E-CDK2 and cyclin A-CDK activities upon release
      from heat-labile complexes. E5/E8 cells also have elevated levels of cyclins D1
      and D3, and high levels of nuclear p27 are tolerated because the inhibitor is
      sequestered within an elevated pool of cyclin D1-CDK4 complexes, a significant
      portion of which retain kinase activity. In agreement with this, pRB is
      constitutively hyperphosphorylated in E5/E8 cells in vivo. The increased steady
      state level of p27 is achieved largely through an increased rate of protein
      synthesis and does not rely on changes in p27 mRNA levels or protein half-life.
      This is the first report of enhanced p27 synthesis as the main mechanism for
      increasing protein levels in continuously cycling cells. Our results are
      consistent with a model in which E5/E8 promotes a coordinated elevation of cyclin
      D1-CDK4 and p27, as well as cyclin A-associated kinase activity, which act in
      concert to allow continued proliferation in the absence of mitogens.

PMID- 11448949
TI  - Activation of the luteinizing hormone/choriogonadotropin hormone receptor
      promotes ADP ribosylation factor 6 activation in porcine ovarian follicular
      membranes.
AB  - Previously we demonstrated in a cell-free ovarian follicular plasma membrane
      model that agonist-dependent desensitization of the luteinizing
      hormone/choriogonadotropin receptor (LH/CG R) is GTP-dependent, mimicked by the
      addition of ADP-ribosylation factor (ARF) nucleotide binding site opener, which
      acts as a guanine nucleotide exchange factor for ARFs 1 and 6, and selectively
      inhibited by synthetic N-terminal ARF6 peptides. We therefore sought direct
      evidence that activation of the LH/CG R promotes activation of ARF1 and/or ARF6.
      Using a classic ARF activation assay, the cholera toxin-catalyzed ADP
      ribosylation of G alpha(s), results show that LH/CG R activation stimulates an
      ARF protein by a brefeldin A-independent mechanism. Synthetic N-terminal
      inhibitory ARF6 but not ARF1 peptide blocks LH/CG R-stimulated ARF activity.
      LH/CG R activation also promotes the binding of a photoaffinity GTP analog to a
      protein that migrates on one- and two-dimensional polyacrylamide gel
      electrophoresis with ARF6. These results suggest that ARF6 is the predominant ARF
      activated by the LH/CG R. To activate ARF6, the LH/CG R does not appear to signal
      through the C-terminal regions of G alpha(i) or G alpha(q) or through the second
      or third intracellular loops or the N terminus of the cytoplasmic tail of the
      LH/CG R. Although exogenous recombinant ARNO promotes only a small increase in
      ARF6 activation in the presence of activated LH/CG R, hCG-stimulated ARF6
      activation is reduced to basal levels by catalytically inactive ARF nucleotide
      binding-site opener. These results provide direct evidence that LH/CG R
      activation leads to the activation of membrane-delimited ARF6.

PMID- 11448950
TI  - The orphan nuclear receptor small heterodimer partner as a novel coregulator of
      nuclear factor-kappa b in oxidized low density lipoprotein-treated macrophage
      cell line RAW 264.7.
AB  - Small heterodimer partner (SHP), specifically expressed in liver and a limited
      number of other tissues, is an unusual orphan nuclear receptor that lacks the
      conventional DNA binding domain. In this work, we found that SHP expression is
      abundant in murine macrophage cell line RAW 264.7 but was suppressed by oxidized
      low density lipoprotein (oxLDL) and its constituent 13-hydroxyoctadecadienoic
      acid, a ligand for peroxisome proliferator-activated receptor gamma. Furthermore,
      SHP acted as a transcription coactivator of nuclear factor-kappa B (NF kappa B)
      and was essential for the previously described NF kappa B transactivation by
      palmitoyl lysophosphatidylcholine, one of the oxLDL constituents. Accordingly NF
      kappa B, which was transcriptionally active in the beginning, became
      progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP
      expression. Thus, SHP appears to be an important modulatory component to regulate
      the transcriptional activities of NF kappa B in oxLDL-treated, resting macrophage
      cells.

PMID- 11448951
TI  - Identification of tumor necrosis factor (TNF) amino acids crucial for binding to
      the murine p75 TNF receptor and construction of receptor-selective mutants.
AB  - The bioactivity of tumor necrosis factor (TNF) is mediated by two TNF receptors
      (TNF-Rs), more particularly TNF-RI and TNF-RII. Although human TNF (hTNF) and
      murine TNF (mTNF) are very homologous, hTNF binds only to mTNF-RI. By measuring
      the binding of a panel of mTNF/hTNF chimeras to both mTNF-R, we pinpointed the
      TNF region that mediates the interaction with mTNF-RII. Using site-specific
      mutagenesis, we identified amino acids 71-73 and 89 as the main interacting
      residues. Mutein hTNF-S71D/T72Y/H73 Delta/T89E interacts with both types of mTNF
      R and is active in CT6 cell proliferation assays mediated by mTNF-RII. Mutein
      mTNF-D71S/Y72T/Delta 73H/E89T binds to mTNF-RI only and is no longer active on
      CT6 cells. However, the L929s cytotoxicity of this mutein (an effect mediated by
      mTNF-RI triggering) was also 100-fold lower than that of wild-type mTNF due to
      enhanced dissociation during incubation at subnanomolar concentrations. The
      additional mutation of amino acid 102, resulting in the mutein mTNF
      D71S/Y72T/Delta 73H/E89T/P102Q, restored the trimer stability, which led to an
      enhanced specific activity on L929s cells. Hence the specific activity of a TNF
      species is governed not only by its receptor binding characteristics but also by
      its trimer stability after incubation at subnanomolar concentrations. In
      conclusion, the mutation of TNF amino acids 71-73, 89, and 102 is sufficient to
      obtain a mTNF mutein selective for mTNF-RI and a hTNF mutein that, unlike wild
      type hTNF, also acts on mTNF-RII.

PMID- 11448952
TI  - Src-catalyzed phosphorylation of c-Cbl leads to the interdependent ubiquitination
      of both proteins.
AB  - The protooncogene c-Cbl has recently emerged as an E3 ubiquitin ligase for
      activated receptor tyrosine kinases. We report here that c-Cbl also mediates the
      ubiquitination of another protooncogene, the non-receptor tyrosine kinase c-Src,
      as well as of itself. The c-Cbl-dependent ubiquitination of Src and c-Cbl
      requires c-Cbl's RING finger, Src kinase activity, and c-Cbl's tyrosine
      phosphorylation, probably on Tyr-371. In vitro, c-Cbl forms a stable complex with
      the ubiquitin-conjugating enzyme UbcH7, but active Src destabilizes this
      interaction. In contrast, Src inhibition stabilizes the c-Cbl. UbcH7.Src complex.
      Finally, c-Cbl reduces v-Src protein levels and suppresses v-Src-induced STAT3
      activation. Thus, in addition to mediating the ubiquitination of activated
      receptor tyrosine kinases, c-Cbl also acts as a ubiquitin ligase for the non
      receptor tyrosine kinase Src, thereby down-regulating Src.

PMID- 11448953
TI  - Coupling endoplasmic reticulum stress to the cell death program. Mechanism of
      caspase activation.
AB  - The endoplasmic reticulum (ER) is the site of assembly of polypeptide chains
      destined for secretion or routing into various subcellular compartments. It also
      regulates cellular responses to stress and intracellular Ca(2+) levels. A variety
      of toxic insults can result in ER stress that ultimately leads to apoptosis.
      Apoptosis is initiated by the activation of members of the caspase family and
      serves as a central mechanism in the cell death process. The present study was
      carried out to determine the role of caspases in triggering ER stress-induced
      cell death. Treatment of cells with ER stress inducers such as brefeldin-A or
      thapsigargin induces the expression of caspase-12 protein and also leads to
      translocation of cytosolic caspase-7 to the ER surface. Caspase-12, like most
      other members of the caspase family, requires cleavage of the prodomain to
      activate its proapoptotic form. Caspase-7 associates with caspase-12 and cleaves
      the prodomain to generate active caspase-12, resulting in increased cell death.
      We propose that any cellular insult that causes prolonged ER stress may induce
      apoptosis through caspase-7-mediated caspase-12 activation. The data underscore
      the involvement of ER and caspases associated with it in the ER stress-induced
      apoptotic process.

PMID- 11448954
TI  - Differential involvement of the hyaluronan (HA) receptors CD44 and receptor for
      HA-mediated motility in endothelial cell function and angiogenesis.
AB  - Hyaluronan (HA), an important glycosaminoglycan constituent of the extracellular
      matrix, has been implicated in angiogenesis. It appears to exert its biological
      effects through binding interactions with at least two cell surface receptors:
      CD44 and receptor for HA-mediated motility (RHAMM). Recent in vitro studies have
      suggested potential roles for these two molecules in various aspects of
      endothelial function. However, the relative contribution of each receptor to
      endothelial functions critical to angiogenesis and their roles in vivo have not
      been established. We therefore investigated the endothelial expression of these
      proteins and determined the effects of antibodies against RHAMM and CD44 on
      endothelial cell (EC) function and in vivo angiogenesis. Both receptors were
      detected on vascular endothelium in situ, and on the surface of cultured EC.
      Further studies with active blocking antibodies revealed that anti-CD44 but not
      anti-RHAMM antibody inhibited EC adhesion to HA and EC proliferation, whereas
      anti-RHAMM but not CD44 antibody blocked EC migration through the basement
      membrane substrate, Matrigel. Although antibodies against both receptor inhibited
      in vitro endothelial tube formation, only the anti-RHAMM antibody blocked basic
      fibroblast growth factor-induced neovascularization in mice. These data suggest
      that RHAMM and CD44, through interactions with their ligands, are both important
      to processes required for the formation of new blood vessels.

PMID- 11448955
TI  - An inhibitory segment of the catalytic subunit of phosphorylase kinase does not
      act as a pseudosubstrate.
AB  - The C terminus of the catalytic gamma subunit of phosphorylase kinase contains
      two autoinhibitory calmodulin binding domains designated PhK13 and PhK5. These
      peptides inhibit truncated gamma(1-300). Previous data show that PhK13 (residues
      302-326) is a competitive inhibitor with respect to phosphorylase b, with a K(i)
      of 1.8 microm. This result suggests that PhK13 may bind to the active site of
      truncated gamma(1-300). Variants of PhK13 were prepared to localize the
      determinants for interaction with the catalytic fragment gamma(1-300). PhK13-1,
      containing residues 302-312, was found to be a competitive inhibitor with respect
      to phosphorylase b with a K(i) of 6.0 microm. PhK13 has been proposed to function
      as a pseudosubstrate inhibitor with Cys-308 occupying the site that normally
      accommodates the phosphorylatable serine in phosphorylase b. A PhK13-1 variant,
      C308S, was synthesized. Kinetic characterization of this peptide reveals that it
      does not serve as a substrate but is a competitive inhibitor. Additional variants
      were designed based on previous knowledge of phosphorylase kinase substrate
      determinants. Variants were analyzed as substrates and as inhibitors for
      truncated gamma(1-300). Although PhK13-1 does not appear to function as a
      pseudosubstrate, several specificity determinants employed in the recognition of
      phosphorylase b as substrate are utilized in the recognition of PhK13-1 as an
      inhibitor.

PMID- 11448956
TI  - The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival.
AB  - Cardiac hypertrophy is a complex process involving the coordinated actions of
      many genes. In a high throughput screen designed to identify transcripts that are
      actively translated during cardiac hypertrophy, we identified a number of genes
      with established links to hypertrophy, including those coding for Sp3, c-Jun,
      annexin II, cathepsin B, and HB-EGF, thus showing the general utility of the
      screen. Focusing on a candidate transcript that has not been previously linked to
      hypertrophy, we found that protein levels of the tumor suppressor PTEN
      (phosphatase and tensin homologue on chromosome ten) were increased in the
      absence of increased messenger RNA levels. Increased PTEN expression by
      recombinant adenovirus in cultured neonatal rat primary cardiomyocytes caused
      cardiomyocyte apoptosis as evidenced by increased caspase-3 activity and cleaved
      poly(A)DP-ribose polymerase. Expression of PTEN was also able to block growth
      factor signaling through the phosphatidylinositol 3,4,5-triphosphate pathway.
      Surprisingly, expression of a catalytically inactive PTEN mutant led to
      cardiomyocyte hypertrophy, with increased protein synthesis, cell surface area,
      and atrial natriuretic factor expression. This hypertrophy was accompanied by an
      increase in Akt activity and improved cell viability in culture.

PMID- 11448957
TI  - Characterization of sequence determinants within the carboxyl-terminal domain of
      chemokine receptor CCR5 that regulate signaling and receptor internalization.
AB  - The CC chemokine receptor CCR5 mediates chemotaxis of leukocytes and serves as a
      principal co-receptor for macrophage-tropic human immunodeficiency virus type 1.
      To identify determinants on the CCR5 carboxyl-terminal domain that regulate
      receptor signaling and internalization, we generated several CCR5 mutants, which
      were progressively shortened from the COOH terminus or had carboxyl-terminal
      serine, cysteine, or leucine residues substituted by alanine and expressed them
      in RBL-2H3 cells. Using fluorescence resonance energy transfer between beta
      arrestin and CCR5 tagged with cyan and yellow variants of green fluorescent
      protein, we show that high affinity association of the two molecules in living
      cells requires intact carboxyl-terminal serine phosphorylation sites.
      Phosphorylation-deficient truncation or Ser/Ala replacement mutants of CCR5
      mediated a sustained calcium response and enhanced granular enzyme release in
      RANTES-stimulated cells. Carboxyl-terminal serine residues are critically
      involved in CCR5 endocytosis and a dileucine motif, similar to that implicated in
      the regulation of CXCR2 and CXCR4, contributes to the internalization of CCR5 in
      a phosphorylation-independent manner. Despite their prominent role in receptor
      desensitization and internalization, beta-arrestins are dispensable for the CCR5
      mediated stimulation of mitogen-activated protein kinase pathways in RBL-2H3
      cells. We also show that CCR5 is palmitoylated on carboxyl-terminal cysteine
      residues. Inhibition of CCR5 palmitoylation by alanine mutagenesis of cysteines
      or treatment with a palmitate analogue inhibitor profoundly reduces phorbol 12
      myristate 13-acetate- and RANTES-induced receptor phosphorylation, homologous
      desensitization, and internalization. Alanine mutagenesis of serine, cysteine, or
      leucine residues or the limited carboxyl-terminal truncation of CCR5 did not
      impair chemokine-stimulated migration of RBL-2H3 cells. Together these results
      indicate that post-translational modifications of carboxyl-terminal serine and
      cysteine residues have a significant impact on receptor deactivation and
      internalization.

PMID- 11448958
TI  - Recombinant small subunit of smooth muscle myosin light chain phosphatase.
      Molecular properties and interactions with the targeting subunit.
AB  - We expressed the small subunit of smooth muscle myosin light chain phosphatase
      (MPs) in Escherichia coli, and have studied its molecular properties as well as
      its interaction with the targeting subunit (MPt). MPs (M(r) = 18,500) has an
      anomalously low electrophoretic mobility, running with an apparent M(r) of
      approximately 21,000 in sodium dodecyl sulfate-gel electrophoresis. CD
      spectroscopy shows that it is approximately 45% alpha-helix and undergoes a
      cooperative temperature-induced unfolding with a transition midpoint of 73
      degrees C. Limited proteolysis rapidly degrades MPs to a stable C-terminal
      fragment (M(r) = 10,000) that retains most of the helical content. Rotary
      shadowing electron microscopy reveals that it is an elongated protein with two
      domains. Sedimentation velocity measurements show that recombinant MPt (M(r) =
      107,000), intact MPs, and the 10-kDa MPs fragment are all dimeric, and that MPs
      and MPt form a complex with a molar mass consistent with a 1:1 heterodimer.
      Sequence analysis predicts that regions in the C-terminal portions of both MPs
      and MPt have high probabilities for coiled coil formation. A synthetic peptide
      from a region of MPs encompassing residues 77-116 was found to be 100% alpha
      helical, dimeric, and formed a complex with MPt with a molecular mass
      corresponding to a heterodimer. Based on these results, we propose that MPs is an
      elongated molecule with an N-terminal head and a C-terminal stalk domain. It
      dimerizes via a coiled coil interaction in the stalk domain, and interacts with
      MPt via heterodimeric coiled coil formation. Since other proteins with known
      regulatory function toward MP also have predicted coiled coil regions, our
      results suggest that these regulatory proteins target MP via the same coiled coil
      strand exchange mechanism with MPt.

PMID- 11448959
TI  - The cytoprotective effects of the glycoprotein 130 receptor-coupled cytokine,
      cardiotrophin-1, require activation of NF-kappa B.
AB  - Many cell types mount elaborate, compensatory responses to stress that enhance
      survival; however, the intracellular signals that govern these responses are
      poorly understood. Cardiotrophin-1 (CT-1), a stress-induced cytokine, belongs to
      the interleukin-6/glycoprotein 130 receptor-coupled cytokine family. CT-1 is
      released from the heart in response to hypoxic stress, and it protects cardiac
      myocytes from hypoxia-induced apoptosis, thus establishing a central role for
      this cytokine in the cardiac stress response. In the present study, CT-1
      activated p38 and ERK MAPKs as well as Akt in cultured cardiac myocytes; these
      three pathways were activated in a parallel manner. CT-1 also induced the
      degradation of the NF-kappa B cytosolic anchor, I kappa B, as well as the
      translocation of the p65 subunit of NF-kappa B to the nucleus and increased
      expression of an NF-kappa B-dependent reporter gene. Inhibitors of the p38, ERK,
      or Akt pathways each partially reduced CT-1-mediated NF-kappa B activation, as
      well as the cytoprotective effects of CT-1 against hypoxic stress. Together, the
      inhibitors completely blocked CT-1-dependent NF-kappa B activation and
      cytoprotection. A cell-permeable peptide that selectively disrupted NF-kappa B
      activation also completely inhibited the cytoprotective effects of CT-1. These
      results indicate that CT-1 signals through p38, ERK, and Akt in a parallel manner
      to activate NF-kappa B and that NF-kappa B is required for CT-1 to mediate its
      full cytoprotective effects in cardiac myocytes.

PMID- 11448960
TI  - Controlled hypertension, a transgenic toggle switch reveals differential
      mechanisms underlying vascular disease.
AB  - A novel inbred rat model with inducible hypertension has been generated using a
      renin transgene under the transcriptional control of the cytochrome P450, Cyp1a1
      promoter. The degree and duration of hypertension are regulated tightly by
      administration of the natural xenobiotic indole-3 carbinol and can be readily
      reversed. Induction experiments reveal distinct temporal and mechanistic
      responses to hypertensive injury in different vascular beds, which is indicative
      of differential susceptibility of organs to a hypertensive stimulus. The
      mesentery and heart exhibited the greatest sensitivity to damage, and the kidney
      showed an adaptive response prior to the development of malignant hypertensive
      injury. Quantitative analysis of morphological changes induced in mesenteric
      resistance arteries suggest eutrophic remodeling of the vessels. Kinetic evidence
      suggests that locally activated plasma prorenin may play a critical role in
      mediating vascular injury. This model will facilitate studies of the cellular and
      genetic mechanisms underlying vascular injury and repair and provide a basis for
      the identification of novel therapeutic targets for vascular disease.

PMID- 11448961
TI  - Biophysical characterization of interactions involving importin-alpha during
      nuclear import.
AB  - Proteins containing the classical nuclear localization sequences (NLSs) are
      imported into the nucleus by the importin-alpha/beta heterodimer. Importin-alpha
      contains the NLS binding site, whereas importin-beta mediates the translocation
      through the nuclear pore. We characterized the interactions involving importin
      alpha during nuclear import using a combination of biophysical techniques
      (biosensor, crystallography, sedimentation equilibrium, electrophoresis, and
      circular dichroism). Importin-alpha is shown to exist in a monomeric
      autoinhibited state (association with NLSs undetectable by biosensor).
      Association with importin-beta (stoichiometry, 1:1; K(D) = 1.1 x 10(-8) m)
      increases the affinity for NLSs; the importin-alpha/beta complex binds
      representative monopartite NLS (simian virus 40 large T-antigen) and bipartite
      NLS (nucleoplasmin) with affinities (K(D) = 3.5 x 10(-8) m and 4.8 x 10(-8) m,
      respectively) comparable with those of a truncated importin-alpha lacking the
      autoinhibitory domain (T-antigen NLS, K(D) = 1.7 x 10(-8) m; nucleoplasmin NLS,
      K(D) = 1.4 x 10(-8) m). The autoinhibitory domain (as a separate peptide) binds
      the truncated importin-alpha, and the crystal structure of the complex resembles
      the structure of full-length importin-alpha. Our results support the model of
      regulation of nuclear import mediated by the intrasteric autoregulatory sequence
      of importin-alpha and provide a quantitative description of the binding and
      regulatory steps during nuclear import.

PMID- 11448962
TI  - Molecular cloning and induction of bovine prostaglandin E synthase by
      gonadotropins in ovarian follicles prior to ovulation in vivo.
AB  - Prostaglandin E(2) (PGE(2)) is thought to be an ultimate prostaglandin effector
      during the ovulatory process, and the objectives of this study were to clone
      bovine PGE synthase (PGES) and to characterize its regulation by gonadotropins in
      preovulatory follicles in vivo. The bovine PGES complementary DNA (cDNA) was
      shown to contain a 5'-untranslated region of eight base pairs (bp), an open
      reading frame of 462 bp and a 3'-untranslated region of 406 bp. The putative
      bovine PGES open reading frame encodes a 153-amino acid protein that is 85, 78,
      and 78% identical to the human, rat, and mouse PGES homologs, respectively. The
      regulation of PGES during ovulation was studied using three different models in
      vivo: 1) human chorionic gonadotropin (hCG)-induced ovulation during a normal
      estrous cycle; 2) hCG-induced ovulation following ovarian hyperstimulation; and
      3) spontaneous ovulation during natural estrus. Results from semi-quantitative
      reverse transcription-polymerase chain reaction/Southern blotting analyses showed
      that the hCG/luteinizing hormone surge caused a significant increase in PGES
      mRNA. Levels of PGES transcripts were low or undetectable prior to
      hCG/luteinizing hormone but increased markedly 18-24 h after hCG in models 1 and
      2, and 18-24 h after the onset of natural estrus in model 3 (p < 0.05). Analyses
      on isolated preparations of granulosa and theca interna cells indicated that the
      granulosa cell layer was the predominant site of follicular PGES expression. The
      regulation of the protein was studied in the same models using a specific
      antibody raised against a fragment of bovine protein (Delta PGES; from Glu(49) to
      Val(146)). Results from immunoblots showed an induction of bovine PGES (M(r) =
      17,000) 18-24 h after hCG treatment or onset of estrus (p < 0.05). The protein
      was detected in extracts of granulosa cells but not in theca interna.
      Collectively, these results demonstrate that the ovulatory process is associated
      with a gonadotropin-dependent induction of PGES in granulosa cells of ovarian
      follicles in vivo, thus establishing for the first time the regulation of the
      enzyme in a physiological context.

PMID- 11448963
TI  - Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.
AB  - Acid-sensing ion channels (ASICs) are activated by extracellular protons and are
      involved in neurotransmission in the central nervous system, in pain perception,
      as well as in mechanotransduction. Six different ASIC subunits have been cloned
      to date, which are encoded by four genes (ASIC1-ASIC4). Proton-gated currents
      have been described in isolated neurons from sensory ganglia as well as from
      central nervous system. However, it is largely unclear which of the cloned ASIC
      subunits underlie these native proton-gated currents. Recently, a splice variant,
      ASIC-beta, has been described for ASIC1a. In this variant about one-third of the
      protein is exchanged at the N terminus. Here we show that ASIC-beta has a longer
      N terminus than previously reported, extending the sequence divergence between
      ASIC1a and this new variant (ASIC1b). We investigated in detail kinetic and
      selectivity properties of ASIC1b in comparison to ASIC1a. Kinetics is similar for
      ASIC1b and ASIC1a. Ca(2+) permeability of ASIC1a is low, whereas ASIC1b is
      impermeable to Ca(2+). Currents through ASIC1a resemble currents, which have been
      described in sensory and central neurons, whereas the significance of ASIC1b
      remains to be established. Moreover, we show that a pre-transmembrane 1 domain
      controls the permeability to divalent cations in ASIC1, contributing to our
      understanding of the pore structure of these channels.

PMID- 11448964
TI  - Membrane type 1-matrix metalloproteinase is activated during migration of human
      endothelial cells and modulates endothelial motility and matrix remodeling.
AB  - Matrix metalloproteinases are thought to play an important role in endothelial
      cell migration and matrix remodeling. We have used an in vitro wound healing
      migration model and newly generated anti-membrane type 1-matrix metalloproteinase
      (MT1-MMP) monoclonal antibodies (mAbs) to characterize the role of MT1-MMP during
      this process. First, the expression and shedding of MT1-MMP are up-regulated upon
      induction of migration in endothelial cells, as demonstrated by flow cytometry
      and Western blot analysis. Furthermore, MT1-MMP is concentrated at discrete areas
      in migrating endothelial cells, in contrast to the diffuse pattern observed in
      confluent cells. Interestingly, migration of endothelial cells results in the
      stimulation of MT1-MMP activity, as shown by its ability to process pro-MMP-2 and
      to degrade fibrinogen assessed by zymography. Moreover, MT1-MMP-mediated gelatin
      degradation is enriched at migration sites. mAbs generated against the MT1-MMP
      catalytic domain are shown to inhibit MT1-MMP enzymatic activity and to impair
      both phorbol 12-myristate 13-acetate-induced endothelial migration and invasion
      of collagen and fibrin gels. Furthermore, a reduction in the formation of
      capillary tubes in Matrigel is also observed when endothelial cells are
      pretreated with the blocking anti-MT1-MMP mAbs. Altogether, these data
      demonstrate that MT1-MMP plays an important role during endothelial cell
      migration, and its activity can modulate endothelial migration, invasion, and
      formation of capillary tubes during the angiogenic response.

PMID- 11448965
TI  - Ssn6-Tup1 regulates RNR3 by positioning nucleosomes and affecting the chromatin
      structure at the upstream repression sequence.
AB  - The DNA damage inducible gene ribonucleotide reductase (RNR3) is regulated by a
      transcriptional repression mechanism by the recruitment of the Ssn6-Tup1
      corepressor complex to its promoter by the sequence-specific DNA-binding protein
      Crt1. Ssn6-Tup1 is reported to represses transcription by interfering with
      transcription factors, recruiting histone deacetylases, and positioning
      nucleosomes at the promoter of its target genes. Two of the three mechanisms
      involve effects on chromatin structure, and therefore, we have delineated the
      nucleosomal structure of RNR3 in the repressed and derepressed state using
      multiple nuclease mapping strategies. A regular array of positioned nucleosomes
      is detected over the repressed RNR3 promoter that extends into the coding
      sequence. Treating cells with DNA damaging agents or deleting CRT1, SSN6, or TUP1
      derepresses RNR3 transcription, and causes a dramatic disruption of nucleosome
      positioning over its promoter. Furthermore, derepression of RNR3 correlated with
      changes in nuclease sensitivity within the upstream repression sequence (URS)
      region. Specifically, the loss of a MNase-hypersensitive site, and the appearance
      of strong DNase I hypersensitivity, was observed over the URS. Interestingly, we
      find that the binding of Crt1 to the promoter in the absence of Ssn6 or Tup1 is
      insufficient for nucleosome positioning or regulating chromatin structure at the
      URS; thus, these two functions are strictly dependent upon Ssn6-Tup1. We propose
      that RNR3 is regulated by changes in nucleosome positioning and chromatin
      structure that are mediated by Ssn6, Tup1, and Crt1.

PMID- 11448966
TI  - Engineered biosynthesis of the peptide antibiotic bacitracin in the surrogate
      host Bacillus subtilis.
AB  - Nonribosomal peptides are processed on multifunctional enzymes called
      nonribosomal peptide synthetases (NRPSs), whose modular multidomain arrangement
      allowed the rational design of new peptide products. However, the lack of natural
      competence and efficient transformation methods for most of nonribosomal peptide
      producer strains prevented the in vivo manipulation of these biosynthetic gene
      clusters. In this study, we present methods for the construction of a genetically
      engineered Bacillus subtilis surrogate host for the integration and heterologous
      expression of foreign NRPS genes. In the B. subtilis surrogate host, we deleted
      the resident 26-kilobase srfA gene cluster encoding the surfactin synthetases and
      subsequently used the same chromosomal location for integration of the entire 49
      kilobase bacitracin biosynthetic gene cluster from Bacillus licheniformis by a
      stepwise homologous recombination method. Synthesis of the branched cyclic
      peptide antibiotic bacitracin in the engineered B. subtilis strain was achieved
      at high level, indicating a functional production and proper posttranslational
      modification of the bacitracin synthetases BacABC, as well as the expression of
      the associated bacitracin self-resistance genes. This engineered and genetically
      amenable B. subtilis strain will facilitate the rational design of new bacitracin
      derivatives.

PMID- 11448967
TI  - Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor signals
      through multiple pathways in endothelial cells.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) encodes a
      chemokine-like G protein-coupled receptor (KSHV-GPCR) that is implicated in the
      pathogenesis of Kaposi's sarcoma (KS). Since endothelial cells appear to be
      targets for the virus, we developed an in vitro mouse lung endothelial cell model
      in which KSHV-GPCR is stably expressed and KSHV-GPCR signaling was studied. In
      mouse lung endothelial cells: 1) KSHV-GPCR does not exhibit basal signaling
      through the phosphoinositide-specific phospholipase C pathway but inositol
      phosphate production is stimulated by growth-related oncogene alpha (Gro-alpha)
      via a pertussis toxin (PTX)-insensitive pathway; 2) KSHV-GPCR signals basally
      through a PTX-sensitive pathway leading to a lowering of intracellular cAMP level
      that can be lowered further by Gro alpha and increased by interferon gamma
      inducible protein 10; 3) KSHV-GPCR stimulates phosphatidylinositol 3-kinase via a
      PTX-insensitive mechanism; and 4) KSHV-GPCR activates nuclear factor-kappa B (NF
      kappa B) by a PTX-sensitive G beta gamma subunit-mediated pathway. These data
      show that KSHV-GPCR couples to at least two G proteins and initiates signaling
      via at least three cascades in endothelial cells thereby increasing the
      complexity of regulation of endothelial cell function by KSHV-GPCR that may occur
      during viral infection.

PMID- 11448968
TI  - Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p,
      intracellular iron use and resistance to oxidative stress in yeast.
AB  - The yeast, Saccharomyces cerevisiae, contains a transcription activator, Aft1p,
      that regulates the transcription of the high affinity iron transport system
      genes. This report describes the properties of Aft2p, a protein 39% homologous to
      Aft1p. Aft2p was found to activate transcription. Overproduction of Aft2p
      activates the transcription of the AFT1 target gene FET3. The double aft1aft2
      mutant was unable to grow in iron-deprived conditions. Because a fet3 mutant does
      not show this deficiency, the defect is not solely caused by mis-regulation of
      iron transport but also involves defective iron use by the cells. The aft1 cells
      were unable to grow in aerobic conditions on plates containing raffinose as the
      sole carbon source. The inability to grow on raffinose is not caused by the cell
      iron content being too low to sustain respiratory metabolism, because the oxygen
      consumption of aft1 mutants showed that their respiratory activity is 2-fold
      higher than that of controls. The double aft1aft2 mutant also has many phenotypes
      related to oxidative stress such as H(2)O(2) hypersensitivity, oxygen-dependent
      copper toxicity, and oxygen-dependent methionine auxotrophy, which are suppressed
      in anaerobiosis. These results suggest that Aft2p and Aft1p have overlapping
      roles in the control of iron-regulated pathway(s) connected to oxidative stress
      resistance in yeast.

PMID- 11448969
TI  - Functional interaction between sterol regulatory element-binding protein-1c,
      nuclear factor Y, and 3,5,3'-triiodothyronine nuclear receptors.
AB  - Sterol regulatory element binding protein-1c (SREBP-1c) is a key hepatic
      transcription factor involved in lipogenic gene expression. In an effort to
      understand the role SREBP-1c plays in lipogenic gene transcription, we have
      examined the functional interaction between SREBP-1c, nuclear factor Y, 3,5,3'
      triiodothyronine (T(3)) receptors, and co-activators using the S14 gene promoter
      as a model. T(3), glucose, and insulin rapidly induce S14 gene transcription in
      rat liver and in primary hepatocytes. Linker scanning analyses of the S14
      promoter showed that an SRE at -139/-131 base pairs (bp) binding SREBP-1c and a Y
      box at -104/-99 bp binding NF-Y are indispensable for both T(3)- and SREBP-1c
      mediated induction of S14 promoter activity in rat primary hepatocytes. T(3) and
      glucose/insulin induce S14 gene transcription through separate enhancers.
      Enhancer substitution studies reveal a preferential interaction between SREBP
      1c.NF-Y and the T(3) regulatory region (-2.8/-2.5 kb) binding thyroid hormone
      receptor/RXR heterodimers. Elevating hepatocellular levels of specific co
      activators (CBP, p/CAF, or GCN5) induced S14 promoter activity 2-3-fold, while
      SREBP-1c induced promoter activity 10-fold. The combination of these treatments
      induced S14 promoter activity (20-35-fold). However, this additive effect was
      lost when the T(3) regulatory region was deleted. Based on these results, we
      suggest that the SREBP-1c.NF-Y complex facilitates the interaction between co
      activators that are recruited to distal hormone-regulated enhancers and the
      general transcription machinery that binds the S14 proximal promoter.

PMID- 11448970
TI  - Biochemical basis of type IB (E1beta ) mutations in maple syrup urine disease. A
      prevalent allele in patients from the Druze kindred in Israel.
AB  - Maple syrup urine disease (MSUD) is a metabolic disorder associated with often
      fatal ketoacidosis, neurological derangement, and mental retardation. In this
      study, we identify and characterize two novel type IB MSUD mutations in Israeli
      patients, which affect the E1beta subunit in the decarboxylase (E1) component of
      the branched-chain alpha-ketoacid dehydrogenase complex. The recombinant mutant
      E1 carrying the prevalent S289L-beta (TCG --> TTG) mutation in the Druze kindred
      exists as a stable inactive alphabeta heterodimer. Based on the human E1
      structure, the S289L-beta mutation disrupts the interactions between Ser-289-beta
      and Glu-290-beta', and between Arg-309-beta and Glu-290-beta', which are
      essential for native alpha(2)beta(2) heterotetrameric assembly. The R133P-beta
      (CGG --> CCG) mutation, on the other hand, is inefficiently expressed in
      Escherichia coli as heterotetramers in a temperature-dependent manner. The R133P
      beta mutant E1 exhibits significant residual activity but is markedly less stable
      than the wild-type, as measured by thermal inactivation and free energy change of
      denaturation. The R133P-beta substitution abrogates the coordination of Arg-133
      beta to Ala-95-beta, Glu-96-beta, and Ile-97-beta, which is important for strand
      strand interactions and K(+) ion binding in the beta subunit. These findings
      provide new insights into folding and assembly of human E1 and will facilitate
      DNA-based diagnosis for MSUD in the Israeli population.

PMID- 11448971
TI  - The development-associated cleavage of lens connexin 45.6 by caspase-3-like
      protease is regulated by casein kinase II-mediated phosphorylation.
AB  - Gap junctions are important in maintaining lens transparency and metabolic
      homeostasis. In this paper, we report that the gap junction-forming protein,
      connexin (Cx) 45.6, was specifically truncated during lens development and that
      the majority of the truncated fragments were located in the differentiated lens
      fibers. When isolated lens membranes were treated by caspase-3, the truncated
      fragments of Cx45.6 were reproduced, and this truncation occurred at the COOH
      terminus of Cx45.6. Moreover, when primary lens cells were treated with apoptosis
      inducing reagents, Cx45.6 was cleaved similarly as the in vitro treatment by
      caspase-3, and this cleavage was blocked by a caspase-3 inhibitor. These results
      suggest that caspase-3 is responsible for the development-associated cleavage of
      Cx45.6. The cleavage site of Cx45.6 was identified between amino acid residues
      Glu(367) and Gly(368). We have shown previously that Ser(363) is an in vivo
      phosphorylated site by casein kinase II, and this specific phosphorylation leads
      to a rapid turnover of Cx45.6. Interestingly, we found here that when Ser(363)
      was phosphorylated by casein kinase II, the cleavage of Cx45.6 catalyzed by
      caspase-3 was inhibited. This study, for the first time, demonstrates that a
      connexin can be a direct target of an apoptotic protease and that cleavage by
      caspase-3-like protease leads to the development-associated truncation of a lens
      connexin. Finally, caspase-3-mediated cleavage can be regulated by casein kinase
      II-mediated phosphorylation, suggesting that Cx45.6 turnover and specific
      cleavage by caspase-3-like protease is alternatively modulated.

PMID- 11448982
TI  - Microtubules concentrate.

PMID- 11448985
TI  - Nuclear pore complexes: dynamics in unexpected places.
AB  - In vivo studies on the dynamics of the nuclear pore complex (NPC) in yeast
      suggested that NPCs are highly mobile in the nuclear envelope. However, new
      evidence indicates that in mammalian cells NPCs are stably attached to a flexible
      lamina framework, but a peripheral component can exchange rapidly with an
      intranuclear pool.

PMID- 11448986
TI  - Fishing out proteins that bind to titin.
AB  - Another giant protein has been detected in cross-striated muscle cells. Given the
      name obscurin, it was discovered in a yeast two-hybrid screen in which the bait
      was a small region of titin that is localized near the Z-band. Obscurin is about
      720 kD, similar in molecular weight to nebulin, but present at about one tenth
      the level (Young et al., 2001). Like titin, obscurin contains multiple
      immunoglobulin-like domains linked in tandem, but in contrast to titin it
      contains just two fibronectin-like domains. It also contains sequences that
      suggest obscurin may have roles in signal transduction. During embryonic
      development, its localization changes from the Z-band to the M-band. With these
      intriguing properties, obscurin may not remain obscure for long.

PMID- 11448987
TI  - ZNF265--a novel spliceosomal protein able to induce alternative splicing.
AB  - The formation of the active spliceosome, its recruitment to active areas of
      transcription, and its role in pre-mRNA splicing depends on the association of a
      number of multifunctional serine/arginine-rich (SR) proteins. ZNF265 is an
      arginine/serine-rich (RS) domain containing zinc finger protein with conserved
      pre-mRNA splicing protein motifs. Here we show that ZNF265 immunoprecipitates
      from splicing extracts in association with mRNA, and that it is able to alter
      splicing patterns of Tra2-beta1 transcripts in a dose-dependent manner in HEK 293
      cells. Yeast two-hybrid analysis and immunoprecipitation indicated interaction of
      ZNF265 with the essential splicing factor proteins U1-70K and U2AF(35). Confocal
      microscopy demonstrated colocalization of ZNF265 with the motor neuron gene
      product SMN, the snRNP protein U1-70K, the SR protein SC35, and with the
      transcriptosomal components p300 and YY1. Transfection of HT-1080 cells with
      ZNF265-EGFP fusion constructs showed that nuclear localization of ZNF265 required
      the RS domain. Alignment with other RS domain-containing proteins revealed a high
      degree of SR dipeptide conservation. These data show that ZNF265 functions as a
      novel component of the mRNA processing machinery.

PMID- 11448988
TI  - Large-scale chromatin decondensation and recondensation regulated by
      transcription from a natural promoter.
AB  - We have examined the relationship between transcription and chromatin structure
      using a tandem array of the mouse mammary tumor virus (MMTV) promoter driving a
      ras reporter. The array was visualized as a distinctive fluorescent structure in
      live cells stably transformed with a green fluorescent protein (GFP)-tagged
      glucocorticoid receptor (GR), which localizes to the repeated MMTV elements after
      steroid hormone treatment. Also found at the array by immunofluorescence were two
      different steroid receptor coactivators (SRC1 and CBP) with acetyltransferase
      activity, a chromatin remodeler (BRG1), and two transcription factors (NFI and AP
      2). Within 3 h after hormone addition, arrays visualized by GFP-GR or DNA
      fluorescent in situ hybridization (FISH) decondensed to varying degrees, in the
      most pronounced cases from a approximately 0.5-microm spot to form a fiber 1-10
      microm long. Arrays later recondensed by 3-8 h of hormone treatment. The degree
      of decondensation was proportional to the amount of transcript produced by the
      array as detected by RNA FISH. Decondensation was blocked by two different drugs
      that inhibit polymerase II, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole
      (DRB) and alpha-amanitin. These observations demonstrate a role for polymerase in
      producing and maintaining decondensed chromatin. They also support fiber-packing
      models of higher order structure and suggest that transcription from a natural
      promoter may occur at much higher DNA-packing densities than reported previously.

PMID- 11448989
TI  - Normal telomere length and chromosomal end capping in poly(ADP-ribose) polymerase
      deficient mice and primary cells despite increased chromosomal instability.
AB  - Poly(ADP-ribose) polymerase (PARP)-1, a detector of single-strand breaks, plays a
      key role in the cellular response to DNA damage. PARP-1-deficient mice are
      hypersensitive to genotoxic agents and display genomic instability due to a DNA
      repair defect in the base excision repair pathway. A previous report suggested
      that PARP-1-deficient mice also had a severe telomeric dysfunction consisting of
      telomere shortening and increased end-to-end fusions (d'Adda di Fagagna, F., M.P.
      Hande, W.-M. Tong, P.M. Lansdorp, Z.-Q. Wang, and S.P. Jackson. 1999. NAT: Genet.
      23:76-80). In contrast to that, and using a panoply of techniques, including
      quantitative telomeric (Q)-FISH, we did not find significant differences in
      telomere length between wild-type and PARP-1(-/)- littermate mice or PARP-1(-/)-
      primary cells. Similarly, there were no differences in the length of the G-strand
      overhang. Q-FISH and spectral karyotyping analyses of primary PARP-1(-/)- cells
      showed a frequency of 2 end-to-end fusions per 100 metaphases, much lower than
      that described previously (d'Adda di Fagagna et al., 1999). This low frequency of
      end-to-end fusions in PARP-1(-/)- primary cells is accordant with the absence of
      severe proliferative defects in PARP-1(-/)- mice. The results presented here
      indicate that PARP-1 does not play a major role in regulating telomere length or
      in telomeric end capping, and the chromosomal instability of PARP-1(-/)- primary
      cells can be explained by the repair defect associated to PARP-1 deficiency.
      Finally, no interaction between PARP-1 and the telomerase reverse transcriptase
      subunit, Tert, was found using the two-hybrid assay.

PMID- 11448990
TI  - A role for nuclear lamins in nuclear envelope assembly.
AB  - The molecular interactions responsible for nuclear envelope assembly after
      mitosis are not well understood. In this study, we demonstrate that a peptide
      consisting of the COOH-terminal domain of Xenopus lamin B3 (LB3T) prevents
      nuclear envelope assembly in Xenopus interphase extracts. Specifically, LB3T
      inhibits chromatin decondensation and blocks the formation of both the nuclear
      lamina-pore complex and nuclear membranes. Under these conditions, some vesicles
      bind to the peripheral regions of the chromatin. These "nonfusogenic" vesicles
      lack lamin B3 (LB3) and do not bind LB3T; however, "fusogenic" vesicles
      containing LB3 can bind LB3T, which blocks their association with chromatin and,
      subsequently, nuclear membrane assembly. LB3T also binds to chromatin in the
      absence of interphase extract, but only in the presence of purified LB3.
      Additionally, we show that LB3T inhibits normal lamin polymerization in vitro.
      These findings suggest that lamin polymerization is required for both chromatin
      decondensation and the binding of nuclear membrane precursors during the early
      stages of normal nuclear envelope assembly.

PMID- 11448991
TI  - Nuclear pore complexes form immobile networks and have a very low turnover in
      live mammalian cells.
AB  - The nuclear pore complex (NPC) and its relationship to the nuclear envelope (NE)
      was characterized in living cells using POM121-green fluorescent protein (GFP)
      and GFP-Nup153, and GFP-lamin B1. No independent movement of single pore
      complexes was found within the plane of the NE in interphase. Only large arrays
      of NPCs moved slowly and synchronously during global changes in nuclear shape,
      strongly suggesting mechanical connections which form an NPC network. The nuclear
      lamina exhibited identical movements. NPC turnover measured by fluorescence
      recovery after photobleaching of POM121 was less than once per cell cycle. Nup153
      association with NPCs was dynamic and turnover of this nucleoporin was three
      orders of magnitude faster. Overexpression of both nucleoporins induced the
      formation of annulate lamellae (AL) in the endoplasmic reticulum (ER). Turnover
      of AL pore complexes was much higher than in the NE (once every 2.5 min). During
      mitosis, POM121 and Nup153 were completely dispersed and mobile in the ER
      (POM121) or cytosol (Nup153) in metaphase, and rapidly redistributed to an
      immobilized pool around chromatin in late anaphase. Assembly and immobilization
      of both nucleoporins occurred before detectable recruitment of lamin B1, which is
      thus unlikely to mediate initiation of NPC assembly at the end of mitosis.

PMID- 11448992
TI  - Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S
      phase and prevents the premature expression of Cdc20p.
AB  - Cell cycle progression is driven by waves of cyclin expression coupled with
      regulated protein degradation. An essential step for initiating mitosis is the
      inactivation of proteolysis mediated by the anaphase-promoting complex/cyclosome
      (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APC(Cdh1) was proposed
      previously to be inactivated at Start by G1 cyclin/cyclin-dependent kinase (CDK).
      Here, we demonstrate that in a normal cell cycle APC(Cdh1) is inactivated in a
      graded manner and is not extinguished until S phase. Complete inactivation of
      APC(Cdh1) requires S phase cyclins. Further, persistent APC(Cdh1) activity
      throughout G1 helps to ensure the proper timing of Cdc20p expression. This
      suggests that S phase cyclins have an important role in allowing the accumulation
      of mitotic cyclins and further suggests a regulatory loop among S phase cyclins,
      APC(Cdh1), and APC(Cdc20).

PMID- 11448993
TI  - The Toxoplasma gondii protein ROP2 mediates host organelle association with the
      parasitophorous vacuole membrane.
AB  - Toxoplasma gondii replicates within a specialized vacuole surrounded by the
      parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with
      host mitochondria and endoplasmic reticulum (ER) in a process termed PVM
      organelle association. In this study we identify a likely mediator of this
      process, the parasite protein ROP2. ROP2, which is localized to the PVM, is
      secreted from anterior organelles termed rhoptries during parasite invasion into
      host cells. The NH(2)-terminal domain of ROP2 (ROP2hc) within the PVM is exposed
      to the host cell cytosol, and has characteristics of a mitochondrial targeting
      signal. In in vitro assays, ROP2hc is partially translocated into the
      mitochondrial outer membrane and behaves like an integral membrane protein.
      Although ROP2hc does not translocate across the ER membrane, it does exhibit
      carbonate-resistant binding to this organelle. In vivo, ROP2hc expressed as a
      soluble fragment in the cytosol of uninfected cells associates with both
      mitochondria and ER. The 30-amino acid (aa) NH(2)-terminal sequence of ROP2hc,
      when fused to green fluorescent protein (GFP), is sufficient for mitochondrial
      targeting. Deletion of the 30-aa NH(2)-terminal signal from ROP2hc results in
      robust localization of the truncated protein to the ER. These results demonstrate
      a new mechanism for tight association of different membrane-bound organelles
      within the cell cytoplasm.

PMID- 11448994
TI  - Human Vam6p promotes lysosome clustering and fusion in vivo.
AB  - Regulated fusion of mammalian lysosomes is critical to their ability to acquire
      both internalized and biosynthetic materials. Here, we report the identification
      of a novel human protein, hVam6p, that promotes lysosome clustering and fusion in
      vivo. Although hVam6p exhibits homology to the Saccharomyces cerevisiae vacuolar
      protein sorting gene product Vam6p/Vps39p, the presence of a citron homology
      (CNH) domain at the NH(2) terminus is unique to the human protein. Overexpression
      of hVam6p results in massive clustering and fusion of lysosomes and late
      endosomes into large (2-3 microm) juxtanuclear structures. This effect is
      reminiscent of that caused by expression of a constitutively activated Rab7.
      However, hVam6p exerts its effect even in the presence of a dominant-negative
      Rab7, suggesting that it functions either downstream of, or in parallel to, Rab7.
      Data from gradient fractionation, two-hybrid, and coimmunoprecipitation analyses
      suggest that hVam6p is a homooligomer, and that its self-assembly is mediated by
      a clathrin heavy chain repeat domain in the middle of the protein. Both the CNH
      and clathrin heavy chain repeat domains are required for induction of lysosome
      clustering and fusion. This study implicates hVam6p as a mammalian
      tethering/docking factor characterized with intrinsic ability to promote lysosome
      fusion in vivo.

PMID- 11448995
TI  - Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein
      involved in sarcomere assembly.
AB  - Vertebrate-striated muscle is assumed to owe its remarkable order to the
      molecular ruler functions of the giant modular signaling proteins, titin and
      nebulin. It was believed that these two proteins represented unique results of
      protein evolution in vertebrate muscle. In this paper we report the
      identification of a third giant protein from vertebrate muscle, obscurin, encoded
      on chromosome 1q42. Obscurin is approximately 800 kD and is expressed
      specifically in skeletal and cardiac muscle. The complete cDNA sequence of
      obscurin reveals a modular architecture, consisting of >67 intracellular
      immunoglobulin (Ig)- or fibronectin-3-like domains with multiple splice variants.
      A large region of obscurin shows a modular architecture of tandem Ig domains
      reminiscent of the elastic region of titin. The COOH-terminal region of obscurin
      interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region
      of titin. Both proteins coassemble during myofibrillogenesis. During the
      progression of myofibrillogenesis, all obscurin epitopes become detectable at the
      M band. The presence of a calmodulin-binding IQ motif, and a Rho guanine
      nucleotide exchange factor domain in the COOH-terminal region suggest that
      obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal
      transduction in the sarcomere.

PMID- 11448996
TI  - Myosin II dynamics and cortical flow during contractile ring formation in
      Dictyostelium cells.
AB  - Myosin II is a major component of a contractile ring. To examine if myosin II
      turns over in contractile rings, fluorescence of GFP-myosin II expressed in
      Dictyostelium cells was bleached locally by laser illumination, and the recovery
      was monitored. The fluorescence recovered with a half time of 7.01 +/- 2.62 s.
      This recovery was not caused by lateral movement of myosin II from the
      nonbleached area, but by an exchange with endoplasmic myosin II. Similar
      experiments were performed in cells expressing GFP-3ALA myosin II, of which three
      phosphorylatable threonine residues were replaced with alanine residues. In this
      case, recovery was not detected within a comparable time range. These results
      indicate that myosin II in the contractile ring performs dynamic turnover via its
      heavy chain phosphorylation. Because GFP-3ALA myosin II did not show the
      recovery, it served as a useful marker of myosin II movement, which enabled us to
      demonstrate cortical flow of myosin II toward the equator for the first time.
      Thus, cortical flow accompanies the dynamic exchange of myosin II during the
      formation of contractile rings.

PMID- 11448997
TI  - RhoA is required for monocyte tail retraction during transendothelial migration.
AB  - Transendothelial migration of monocytes is the process by which monocytes leave
      the circulatory system and extravasate through the endothelial lining of the
      blood vessel wall and enter the underlying tissue. Transmigration requires
      coordination of alterations in cell shape and adhesive properties that are
      mediated by cytoskeletal dynamics. We have analyzed the function of RhoA in the
      cytoskeletal reorganizations that occur during transmigration. By loading
      monocytes with C3, an inhibitor of RhoA, we found that RhoA was required for
      transendothelial migration. We then examined individual steps of transmigration
      to explore the requirement for RhoA in extravasation. Our studies showed that
      RhoA was not required for monocyte attachment to the endothelium nor subsequent
      spreading of the monocyte on the endothelial surface. Time-lapse video microscopy
      analysis revealed that C3-loaded monocytes also had significant forward crawling
      movement on the endothelial monolayer and were able to invade between neighboring
      endothelial cells. However, RhoA was required to retract the tail of the
      migrating monocyte and complete diapedesis. We also demonstrate that p160ROCK, a
      serine/threonine kinase effector of RhoA, is both necessary and sufficient for
      RhoA-mediated tail retraction. Finally, we find that p160ROCK signaling
      negatively regulates integrin adhesions and that inhibition of RhoA results in an
      accumulation of beta2 integrin in the unretracted tails.

PMID- 11448998
TI  - The LD4 motif of paxillin regulates cell spreading and motility through an
      interaction with paxillin kinase linker (PKL).
AB  - The small GTPases of the Rho family are intimately involved in integrin-mediated
      changes in the actin cytoskeleton that accompany cell spreading and motility. The
      exact means by which the Rho family members elicit these changes is unclear.
      Here, we demonstrate that the interaction of paxillin via its LD4 motif with the
      putative ARF-GAP paxillin kinase linker (PKL) (Turner et al., 1999), is
      critically involved in the regulation of Rac-dependent changes in the actin
      cytoskeleton that accompany cell spreading and motility. Overexpression of a
      paxillin LD4 deletion mutant (paxillinDeltaLD4) in CHO.K1 fibroblasts caused the
      generation of multiple broad lamellipodia. These morphological changes were
      accompanied by an increase in cell protrusiveness and random motility, which
      correlated with prolonged activation of Rac. In contrast, directional motility
      was inhibited. These alterations in morphology and motility were dependent on a
      paxillin-PKL interaction. In cells overexpressing paxillinDeltaLD4 mutants, PKL
      localization to focal contacts was disrupted, whereas that of focal adhesion
      kinase (FAK) and vinculin was not. In addition, FAK activity during spreading was
      not compromised by deletion of the paxillin LD4 motif. Furthermore,
      overexpression of PKL mutants lacking the paxillin-binding site (PKLDeltaPBS2)
      induced phenotypic changes reminiscent of paxillinDeltaLD4 mutant cells. These
      data suggest that the paxillin association with PKL is essential for normal
      integrin-mediated cell spreading, and locomotion and that this interaction is
      necessary for the regulation of Rac activity during these events.

PMID- 11448999
TI  - Vav2 is required for cell spreading.
AB  - Vav2 is a widely expressed Rho family guanine nucleotide exchange factor highly
      homologous to Vav1 and Vav3. Activated versions of Vav2 are transforming, but the
      normal function of Vav2 and how it is regulated are not known. We investigated
      the pathways that regulate Vav2 exchange activity in vivo and characterized its
      function. Overexpression of Vav2 activates Rac as assessed by both direct
      measurement of Rac-GTP and cell morphology. Vav2 also catalyzes exchange for
      RhoA, but does not cause morphologic changes indicative of RhoA activation. Vav2
      nucleotide exchange is Src-dependent in vivo, since the coexpression of Vav2 and
      dominant negative Src, or treatment with the Src inhibitor PP2, blocks both Vav2
      dependent Rac activation and lamellipodia formation. A mutation in the pleckstrin
      homology (PH) domain eliminates exchange activity and this construct does not
      induce lamellipodia, indicating the PH domain is necessary to catalyze nucleotide
      exchange. To further investigate the function of Vav2, we mutated the dbl
      homology (DH) domain and asked whether this mutant would function as a dominant
      negative to block Rac-dependent events. Studies using this mutant indicate that
      Vav2 is not necessary for platelet-derived growth factor- or epidermal growth
      factor-dependent activation of Rac. The Vav2 DH mutant did act as a dominant
      negative to inhibit spreading of NIH3T3 cells on fibronectin, specifically by
      blocking lamellipodia formation. These findings indicate that in fibroblasts Vav2
      is necessary for integrin, but not growth factor-dependent activation of Rac
      leading to lamellipodia.

PMID- 11449000
TI  - Targeted ablation of NrCAM or ankyrin-B results in disorganized lens fibers
      leading to cataract formation.
AB  - The NgCAM-related cell adhesion molecule (NrCAM) is an immunoglobulin superfamily
      member of the L1 subgroup that interacts intracellularly with ankyrins. We reveal
      that the absence of NrCAM causes the formation of mature cataracts in the mouse,
      whereas significant pathfinding errors of commissural axons at the midline of the
      spinal cord or of proprioceptive axon collaterals are not detected. Cataracts,
      the most common cause of visual impairment, are generated in NrCAM-deficient mice
      by a disorganization of lens fibers, followed by cellular disintegration and
      accumulation of cellular debris. The disorganization of fiber cells becomes
      histologically distinct during late embryonic development and includes
      abnormalities of the cytoskeleton and of connexin50-containing gap junctions.
      Furthermore, analysis of lenses of ankyrin-B mutant mice also reveals a
      disorganization of lens fibers at postnatal day 1, indistinguishable from that
      generated by the absence of NrCAM, indicating that NrCAM and ankyrin-B are
      required to maintain contact between lens fiber cells. Also, these studies
      provide genetic evidence of an interaction between NrCAM and ankyrin-B.

PMID- 11449001
TI  - A novel role for FGF and extracellular signal-regulated kinase in gap junction
      mediated intercellular communication in the lens.
AB  - Gap junction-mediated intercellular coupling is higher in the equatorial region
      of the lens than at either pole, a property believed to be essential for lens
      transparency. We show that fibroblast growth factor (FGF) upregulates gap
      junctional intercellular dye transfer in primary cultures of embryonic chick lens
      cells without detectably increasing either gap junction protein (connexin)
      synthesis or assembly. Insulin and insulin-like growth factor 1, as potent as FGF
      in inducing lens cell differentiation, had no effect on gap junctions. FGF
      induced sustained activation of extracellular signal-regulated kinase (ERK) in
      lens cells, an event necessary and sufficient to increase gap junctional
      coupling. We also identify vitreous humor as an in vivo source of an FGF-like
      intercellular communication-promoting activity and show that FGF-induced ERK
      activation in the intact lens is higher in the equatorial region than in polar
      and core fibers. These findings support a model in which regional differences in
      FGF signaling through the ERK pathway lead to the asymmetry in gap junctional
      coupling required for proper lens function. Our results also identify
      upregulation of intercellular communication as a new function for sustained ERK
      activation and change the current paradigm that ERKs only negatively regulate gap
      junction channel activity.

PMID- 11449002
TI  - Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap
      junctions.
AB  - Connexin 43 (Cx43alpha1) gap junction has been shown to have an essential role in
      mediating functional coupling of neural crest cells and in modulating neural
      crest cell migration. Here, we showed that N-cadherin and wnt1 are required for
      efficient dye coupling but not for the expression of Cx43alpha1 gap junctions in
      neural crest cells. Cell motility was found to be altered in the N-cadherin
      deficient neural crest cells, but the alterations were different from that
      elicited by Cx43alpha1 deficiency. In contrast, wnt1-deficient neural crest cells
      showed no discernible change in cell motility. These observations suggest that
      dye coupling may not be a good measure of gap junction communication relevant to
      motility. Alternatively, Cx43alpha1 may serve a novel function in motility. We
      observed that p120 catenin (p120ctn), an Armadillo protein known to modulate cell
      motility, is colocalized not only with N-cadherin but also with Cx43alpha1.
      Moreover, the subcellular distribution of p120ctn was altered with N-cadherin or
      Cx43alpha1 deficiency. Based on these findings, we propose a model in which
      Cx43alpha1 and N-cadherin may modulate neural crest cell motility by engaging in
      a dynamic cross-talk with the cell's locomotory apparatus through p120ctn
      signaling.

PMID- 11449003
TI  - Multiple cadherin extracellular repeats mediate homophilic binding and adhesion.
AB  - The extracellular homophilic-binding domain of the cadherins consists of 5
      cadherin repeats (EC1-EC5). Studies on cadherin specificity have implicated the
      NH(2)-terminal EC1 domain in the homophilic binding interaction, but the roles of
      the other extracellular cadherin (EC) domains have not been evaluated. We have
      undertaken a systematic analysis of the binding properties of the entire cadherin
      extracellular domain and the contributions of the other EC domains to homophilic
      binding. Lateral (cis) dimerization of the extracellular domain is thought to be
      required for adhesive function. Sedimentation analysis of the soluble
      extracellular segment of C-cadherin revealed that it exists in a monomer-dimer
      equilibrium with an affinity constant of approximately 64 microm. No higher order
      oligomers were detected, indicating that homophilic binding between cis-dimers is
      of significantly lower affinity. The homophilic binding properties of a series of
      deletion constructs, lacking successive or individual EC domains fused at the
      COOH terminus to an Fc domain, were analyzed using a bead aggregation assay and a
      cell attachment-based adhesion assay. A protein with only the first two NH(2)
      terminal EC domains (CEC1-2Fc) exhibited very low activity compared with the
      entire extracellular domain (CEC1-5Fc), demonstrating that EC1 alone is not
      sufficient for effective homophilic binding. CEC1-3Fc exhibited high activity,
      but not as much as CEC1-4Fc or CEC1-5Fc. EC3 is not required for homophilic
      binding, however, since CEC1-2-4Fc and CEC1-2-4-5Fc exhibited high activity in
      both assays. These and experiments using additional EC combinations show that
      many, if not all, the EC domains contribute to the formation of the cadherin
      homophilic bond, and specific one-to-one interaction between particular EC
      domains may not be required. These conclusions are consistent with a previous
      study on direct molecular force measurements between cadherin ectodomains
      demonstrating multiple adhesive interactions (Sivasankar, S., W. Brieher, N.
      Lavrik, B. Gumbiner, and D. Leckband. 1999. PROC: Natl. Acad. Sci. USA. 96:11820
      11824; Sivasankar, S., B. Gumbiner, and D. Leckband. 2001. Biophys J. 80:1758
      68). We propose new models for how the cadherin extracellular repeats may
      contribute to adhesive specificity and function.

PMID- 11449007
TI  - How do women cope with family violence? Moving ahead in our understanding of
      international issues.

PMID- 11449008
TI  - Meeting the health needs of young people.

PMID- 11449009
TI  - Glossary on meta-analysis.

PMID- 11449010
TI  - Polychlorinated biphenyls (PCBs) and neurological development in children: a
      systematic review.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are complex mixtures of persistent
      contaminants that are widespread in the environment. Newborns are exposed across
      the placenta and through breast feeding. Experimental animal studies have
      indicated that PCBs are neurotoxic. The neurological effects of these compounds
      on children are not clear. METHODS: A systematic review of literature on the
      relation between neurological development in children and exposure to
      polychlorinated biphenyls. RESULTS: Seven follow up studies evaluated the effect
      of prenatal exposure to PCBs. Two of these studies evaluated highly exposed
      children. In newborns, an increase of the abnormal reflexes was observed in all
      four studies evaluating it. During the first months of life, a decrease in motor
      skills was observed in four of the five studies that investigated psychomotor
      development; deficits in the acquisition of cognitive skills were observed only
      in one study assessing non-highly exposed populations. At 4 years of age, an
      effect on the cognitive areas was observed in four of the five studies that
      evaluated it. Postnatal exposure to PCBs through breast feeding was not clearly
      related to any effect on neurological development. CONCLUSIONS: These studies
      suggest a subtle adverse effect of prenatal PCBs exposure on child
      neurodevelopment. Differences in study design, inconsistency in some of the
      results, and the lack of adequate quantitative exposure data, do not allow the
      derivation of the degree of risk associated with neurodevelopmental effects at
      current levels of exposure.

PMID- 11449011
TI  - Women's strategic responses to violence in Nicaragua.
AB  - STUDY OBJECTIVE: To describe the responses of women in Leon, Nicaragua to partner
      abuse and identify contextual factors associated with the use of certain coping
      mechanisms and the likelihood of permanent separation. DESIGN: Cross sectional
      population-based survey. SETTING: Leon, Nicaragua. PARTICIPANTS: 188 women 15-49
      years of age who had experienced physical partner abuse, out of 488 women
      interviewed. MAIN RESULTS: 66% of women defended themselves effectively from
      abuse either physically or verbally. Forty one per cent of women had left home
      temporarily because of violence and 20% had sought help outside the home. Women
      experiencing severe abuse were more likely to leave or seek help, whereas women
      with less severe abuse were more able to defend themselves effectively. Seventy
      per cent of women eventually left abusive relationships. Help seeking and
      temporary separations increased the likelihood of a permanent separation, whereas
      women who defended themselves and were able to stop the violence, at least
      temporarily, were more likely to remain in abusive relationships. CONCLUSIONS:
      Women in Nicaragua use a variety of methods in order to overcome physical partner
      abuse. Temporary leaving and help seeking are critical steps in the process of
      leaving a violent relationship. However, many women indicated that they did not
      receive support for their situation. More interventions are needed to help women
      recognise and deal with violence, as well as strengthening the community support
      networks available to abused women.

PMID- 11449012
TI  - The role of income differences in explaining social inequalities in self rated
      health in Sweden and Britain.
AB  - STUDY OBJECTIVE: To analyse to what extent differences in income, using two
      distinct measures-as distribution across quintiles and poverty-explain social
      inequalities in self rated health, for men and women, in Sweden and Britain.
      DESIGN: Series of cross sectional surveys, the Swedish Survey of Living
      Conditions (ULF) and the British General Household Survey (GHS), during the
      period 1992-95. PARTICIPANTS AND SETTING: Swedish and British men and women aged
      25-64 years. Approximately 4000 Swedes and 12 500 Britons are interviewed each
      year in the cross sectional studies used. The sample contains 15 766 people in
      the Swedish dataset and 49 604 people in the British dataset. MAIN RESULTS: The
      magnitude of social inequalities in less than good self rated health was similar
      in Sweden and in Britain, but adjusting for income differences explained a
      greater part of these in Britain than in Sweden. In Britain the distribution
      across income quintiles explained 47% of the social inequalities in self rated
      health among women and 31% among men, while in Sweden it explained, for women 13%
      and for men 20%. Poverty explained 22% for British women and 8% for British men
      of the social inequalities in self rated health, while in Sweden poverty
      explained much less (men 2.5% and women 0%). CONCLUSIONS: The magnitude of social
      inequalities in self rated health was similar in Sweden and in Britain. However,
      the distribution of income across occupational social classes explains a larger
      part of these inequalities in Britain than in Sweden. One reason for this may be
      the differential exposure to low income and poverty in the two countries.

PMID- 11449013
TI  - Educational level and decreases in leisure time physical activity: predictors
      from the longitudinal GLOBE study.
AB  - STUDY OBJECTIVE: This study describes educational differences in decreases in
      leisure time physical activity among an adult, physically active population and
      additionally attempts to identify predictors of these differences from
      information on health status and individual and environmental factors. DESIGN:
      Prospective population based study. Baseline measurement were carried out in 1991
      and follow up in 1997. SETTING: South eastern part of the Netherlands.
      PARTICIPANTS: The study included 3793 subjects who were physically active in 1991
      and who participated in the follow up. METHODS: Potential predictors of
      decreasing physical activity were measured in 1991. Logistic regression analyses
      were carried out for two age groups (< 45 years; > or = 45 years) separately.
      MAIN RESULTS: Lower educated respondents experienced statistically significant
      higher odds to decrease physical activity during follow up, compared with
      respondents with higher vocational schooling or a university degree. Perceived
      control was the main predictor of educational differences in decreasing physical
      activity in both age groups. In the older group, material problems and a poor
      perceived health experienced by lower educated people additionally predicted
      educational differences in decreases in physical activity during leisure time.
      CONCLUSIONS: These findings have important implications for health promotion
      practice and policy to prevent socioeconomic differences in physical inactivity
      and health. There is a need for evidence-based interventions that improve
      perceived control and reduce material problems in lower educated groups.

PMID- 11449014
TI  - Participation of epidemiologists and/or biostatisticians and methodological
      quality of published controlled clinical trials.
AB  - STUDY OBJECTIVE: This study assessed several methodological aspects related to
      the quality of published controlled clinical trials (CCTs) in relation to the
      participation of an epidemiologist/biostatistician (E/B). DESIGN: Handsearch of
      CCTs published in four medical leading journals for 1993-1995. METHODS: Quality
      variables, abstracted from a review, were related to authors' specialties. Five
      hundred and ninety four CCTs were identified via a hand search. The
      department/unit membership was used to attribute authors' specialties. Of 594
      CCTs identified, in 127 the authors' specialties could not be known, leaving 467
      trials for analysis. RESULTS: E/B participation occurred in 178 trials (38.1%).
      This participation was more frequent in multicentric, bigger, and in those trials
      describing any funding agency. These factors were controlled for in the analysis.
      E/B participation was positively associated with pre-study sample size estimation
      (OR = 1.5, 95% confidence intervals (CI) 1.0, 2.3), with reporting the dates for
      starting/ending the study (OR = 2.1, 95% CI 1.4, 3.3), with using an objectively
      assessed outcome (OR = 2.4, 95% CI 1.2, 4.6) and with the intention to treat
      principle (OR = 2.0, 95% CI 1.3, 3.0). The overall quality score was higher in
      trials where E/B participated. CONCLUSIONS: The results suggest that E/B improve
      the quality (at least of reports) of clinical trials. Given that quality of
      research is frequently used to evaluate potential sources of heterogeneity
      between trials, these results are relevant for meta-analysis.

PMID- 11449015
TI  - Cigarette smoking, alcohol intoxication and major depressive episode in a
      representative population sample.
AB  - OBJECTIVE: This study investigated the associations of cigarette smoking and
      alcohol intoxication with major depressive episode. DESIGN: Major depressive
      episode during the past 12 months was assessed in a national representative cross
      sectional study using the Short Form of the University of Michigan version of the
      Composite International Diagnostic Interview (the UM-CIDI Short Form). SUBJECTS:
      A random sample of 5993 non-institutionalised Finnish people aged 15-75 years was
      interviewed as a part of the 1996 Finnish Health Care Survey. RESULTS: In
      logistic regression models the factors associated with major depressive episode
      in the past 12 months were smoking 10 or more cigarettes daily (odds ratio (OR)
      2.26; 95% confidence intervals (95% CI) 1.68, 3.04) and alcohol intoxication at
      least once a week (OR 2.99; 95%CI 1.70, 5.25). Their effects were independent of
      each other, and remained significant even after adjusting for other major risk
      factors (marital status, education, unemployment and chronic diseases). The
      attributable proportion (a measure of the impact of the risk factors of the
      disease on the population) for daily smoking of 10 or more cigarettes was 0.15,
      and for alcohol intoxication at least once a week 0.04. CONCLUSION: Cigarette
      smoking and alcohol intoxication seem to be important risk factors for major
      depressive episode. In this population the impact of smoking was greater.

PMID- 11449016
TI  - Trends in young adult mortality in three European cities: Barcelona, Bologna and
      Munich, 1986-1995.
AB  - OBJECTIVE: In recent decades, in most European countries young adult mortality
      has risen, or at best has remained stable. The aim of this study was to describe
      trends in mortality attributable to the principal causes of death: AIDS, drug
      overdose, suicide and motor vehicle traffic accidents, among adults aged between
      15 and 34 years in three European cities (Barcelona, Bologna and Munich), over
      the period 1986 to 1995. METHODS: The population studied consisted of all deaths
      that occurred between 1986 and 1995 among residents of Barcelona, Bologna and
      Munich aged from 15 to 34 years. Information about deaths was obtained from
      mortality registers. The study variables were sex, age, the underlying cause of
      death and year of death. Causes of death studied were: drug overdose, AIDS,
      suicide and motor vehicle traffic accidents. Age standardised mortality rates
      (direct adjustment) were obtained in all three cities for the age range 15-34. To
      investigate trends in mortality over the study period Poisson regression models
      were fitted, obtaining the average relative risk (RR) associated with a one year
      increment. RESULTS: Young adult mortality increased among men in Barcelona and
      Bologna (RR per year: 1.04, 95% confidence intervals (95%CI): 1.03, 1.06 in
      Barcelona and RR:1.03, 95%CI:1.01, 1.06 in Bologna) and among women in Barcelona
      (RR:1.02, 95%CI: 1.01, 1.04), with a change in the pattern of the main causes of
      death attributable to the increase in AIDS and drug overdose mortality. In
      Munich, the pattern did not change as much, suicides being the main cause of
      death during the 10 years studied, although they have been decreasing since 1988
      (RR:0.92, 95%CI:0.88, 0.96 for men and 0.81, 95%CI: 0.75-0.87 for women).
      CONCLUSION: The increase in AIDS mortality observed in the three European cities
      in the mid-80s and mid-90s has yielded substantial changes in the pattern of the
      main causes of death at young ages in Barcelona and Bologna. Munich presented a
      more stable pattern, with suicide as the main cause of death.

PMID- 11449017
TI  - Do genetic factors contribute to the association between birth weight and blood
      pressure?
AB  - OBJECTIVES: To evaluate whether genetic factors contribute to the association
      between low birth weight and increased blood pressure among adolescents. DESIGN:
      Historical cohort study of twin pairs. It was evaluated whether (1) a negative
      association between birth weight and systolic blood pressure was found in the
      overall twin sample and (2) whether the intrapair difference in birth weight
      correlated with the intrapair difference in systolic blood pressure-thereby
      controlling for the effect of genetic factors (all in monozygotic and on average
      half in dizygotic pairs). SETTING: The Minnesota Twin Family Study. PARTICIPANTS:
      1311 pairs of adolescent twins. MAIN RESULTS: A negative association between
      birth weight and systolic blood pressure was retrieved in the overall sample. The
      regression coefficient after controlling for current weight was -1.88 mm Hg/kg
      (SE 0.61), which corresponds to results from previous studies of singleton
      adolescents. The regression coefficient fell to -0.64 mm Hg/kg (SE 0.86) when the
      intrapair analyses were used. The largest reduction was observed among
      monozygotic twins: from -2.44 mm Hg/kg (SE 0.75) in the overall monozygotic twin
      sample to -1.06 mm Hg/kg (SE 1.14) in the analyses of the within monozygotic pair
      differences. CONCLUSION: The association between low birth weight and increased
      blood pressure later in life is well established. "The fetal programming
      hypothesis" suggests that the association is caused by intrauterine malnutrition
      while a new hypothesis "the fetal insulin hypothesis" proposes that genetically
      determined insulin resistance also contributes significantly to the association.
      A recent twin study of middle aged twins showed no evidence for an influence of
      genetic factors while this larger study provides support for the fetal insulin
      hypothesis: the association between birth weight and blood pressure attenuated
      among adolescents when genetic factors were controlled. Together this suggests an
      important contribution of genetic factors to the association between fetal growth
      and systolic blood pressure in adolescence.

PMID- 11449018
TI  - Tobacco industry efforts at discrediting scientific knowledge of environmental
      tobacco smoke: a review of internal industry documents.
AB  - STUDY OBJECTIVE: Using tobacco industry internal documents to investigate the use
      of tobacco industry consulting scientists to discredit scientific knowledge of
      environmental tobacco smoke (ETS). DESIGN: Basic and advanced searches were
      performed on the Philip Morris, Tobacco Institute, R J Reynolds, Brown and
      Williamson, Lorillard, and the Council for Tobacco Research document web sites,
      with a concentration on the years 1985-1995. Guildford depository files located
      on the Canadian Council on Tobacco Control website were also searched. The
      documents were found in searches undertaken between 1 March and 30 June 2000.
      MAIN RESULTS: The industry built up networks of scientists sympathetic to its
      position that ETS is an insignificant health risk. Industry lawyers had a large
      role in determining what science would be pursued. The industry funded
      independent organisations to produce research that appeared separate from the
      industry and would boost its credibility. Industry organised symposiums were used
      to publish non-peer reviewed research. Unfavourable research conducted or
      proposed by industry scientists was prevented from becoming public. CONCLUSIONS:
      Industry documents illustrate a deliberate strategy to use scientific consultants
      to discredit the science on ETS.

PMID- 11449019
TI  - Provision of pen along with questionnaire does not increase the response rate to
      a postal survey: a randomised controlled trial.

PMID- 11449020
TI  - Violence: a challenge for public health and for all.

PMID- 11449021
TI  - Economic evaluation of a community based exercise programme to prevent falls.
AB  - OBJECTIVE: To assess the incremental costs and cost effectiveness of implementing
      a home based muscle strengthening and balance retraining programme that reduced
      falls and injuries in older women. DESIGN: An economic evaluation carried out
      within a randomised controlled trial with two years of follow up. Participants
      were individually prescribed an exercise programme (exercise group, n=116) or
      received usual care and social visits (control group, n=117). SETTING: 17 general
      practices in Dunedin, New Zealand. PARTICIPANTS: Women aged 80 years and older
      living in the community and invited by their general practitioner to take part.
      MAIN OUTCOME MEASURES: Number of falls and injuries related to falls, costs of
      implementing the intervention, healthcare service costs resulting from falls and
      total healthcare service costs during the trial. Cost effectiveness was measured
      as the incremental cost of implementing the exercise programme per fall event
      prevented. MAIN RESULTS: 27% of total hospital costs during the trial were
      related to falls. However, there were no significant differences in health
      service costs between the two groups. Implementing the exercise programme for one
      and two years respectively cost $314 and $265 (1995 New Zealand dollars) per fall
      prevented, and $457 and $426 per fall resulting in a moderate or serious injury
      prevented. CONCLUSIONS: The costs resulting from falls make up a substantial
      proportion of the hospital costs for older people. Despite a reduction in falls
      as a result of this home exercise programme there was no significant reduction in
      healthcare costs. However, the results reported will provide information on the
      cost effectiveness of the programme for those making decisions on falls
      prevention strategies.

PMID- 11449022
TI  - Applications of functional imaging to carbon monoxide poisoning.

PMID- 11449023
TI  - The phenomenology of personality change due to traumatic brain injury in children
      and adolescents.
AB  - The authors aimed to contribute a clinically rich description of personality
      change due to traumatic brain injury (PC) in children. The sample consisted of
      consecutively injured children. Ninety-four subjects ages 5 to 14 years were
      assessed at the time of hospitalization after a traumatic brain injury (TBI). A
      standardized psychiatric interview, the Neuropsychiatric Rating Schedule, was
      used to elicit symptoms of PC. PC occurred in 59% of severe (22/37) and 5% of
      mild/moderate (3/57) TBI subjects. Among the 37 severe TBI subjects, the labile
      subtype of PC was the most common (49%), followed by the aggressive and
      disinhibited subtypes (38% each), apathy (14%), and paranoia (5%). Also frequent
      in severe TBI was perseveration (35%). A detailed case example, numerous clinical
      vignettes of PC symptoms, and a tabulation of their frequencies provide
      clinicians a broader frame of reference for eliciting symptoms of PC.

PMID- 11449024
TI  - The clinical role of computerized EEG in the evaluation and treatment of learning
      and attention disorders in children and adolescents.
AB  - Quantitative EEG (QEEG) can play an important role in the evaluation and
      treatment of children and adolescents with attention deficit and learning
      disorders. Children with learning disorders are a heterogeneous population with
      QEEG abnormality in 25% to 45% of reported cases. EEG slowing is the most common
      abnormal finding, and the nature of the QEEG abnormality may be related to future
      academic performance. Children with attention disorders are a more homogeneous
      population, with QEEG abnormalities in up to 80%. In this population,
      frontal/polar regions are most likely to show deviations from normal development,
      with the thalamocortical and/or septal-hippocampal pathways most likely to be
      disturbed. QEEG shows high sensitivity and specificity for distinguishing normal
      children and children with learning disorders and attention disorders from each
      other and may provide useful information for determining the likelihood that
      children with attention problems will respond to treatment with stimulant
      medication.

PMID- 11449025
TI  - Prevalence, clinical manifestations, etiology, and treatment of depression in
      Parkinson's disease.
AB  - To determine the extent to which depression complicates Parkinson's disease (PD),
      the authors analyzed the literature on depression in PD in order to report on its
      prevalence, clinical manifestations, and treatment. By means of MEDLINE
      literature searches, the analysis focused on 45 PD depression studies conducted
      from 1922 through 1998. The results indicate that the prevalence of depression is
      31% for all PD patients. The clinical manifestations of PD depression include
      apathy, psychomotor retardation, memory impairment, pessimism, irrationality, and
      suicidal ideation without suicidal behavior. PD depression is effectively treated
      with a variety of antidepressants, most commonly at present the selective
      serotonin reuptake inhibitors. Anecdotal evidence supports the use of sertraline
      to treat PD depression.

PMID- 11449026
TI  - EEG monitoring in depressed patients undergoing repetitive transcranial magnetic
      stimulation.
AB  - To date, 33 subjects diagnosed with major depressive disorder have undergone
      transcranial magnetic stimulation (TMS) in the authors' clinic. Five of these
      patients showed minimal electroencephalogram (EEG) variants at baseline. The
      authors describe the course of treatment and serial EEGs in 3 of the 5 patients
      who did not show progressive EEG changes in association with active rTMS. These
      three cases suggest that minimal EEG anomalies at baseline need not serve as a
      contraindication to undergoing rTMS. Two patients with progressive EEG changes in
      association with sham rTMS in one and active rTMS in the other are also
      discussed.

PMID- 11449027
TI  - Prefrontal cortex modulation of mood and emotionally induced facial expressions:
      a transcranial magnetic stimulation study.
AB  - Repetitive transcranial magnetic stimulation (rTMS) can serve as a tool to
      experimentally test hypotheses of prefrontal cortex (PFC) modulation of emotions.
      The present study used rTMS to test whether self-rated mood and emotionally
      induced facial expressions are hemispherically lateralized depending on their
      valence, as indicated by previous studies. Healthy volunteers underwent mood self
      rating and computerized analysis of emotionally induced facial expressions before
      and after rTMS of left or right PFC. Facial expression analysis revealed
      lateralized changes of facial expressions after rTMS, whereas changes of
      subjective mood ratings did not show a hemispheric lateralization. On the basis
      of this study, the authors propose to combine rTMS and facial expression analysis
      for further studies of the cortical modulation of emotions in humans.

PMID- 11449028
TI  - Reduced hippocampal volume in association with p50 nonsuppression following
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) may produce persistently impaired auditory gating.
      This cholinergic-dependent, hippocampally mediated preattentive cognitive
      function that facilitates filtering of auditory stimuli may be indexed by the P50
      evoked waveform to paired auditory stimuli. Abnormal P50 suppression post TBI is
      believed to result from injury to the hippocampus and/or its afferent cholinergic
      projections. This hypothesis was tested by comparing hippocampal and total brain
      volumes on MRI between ten P50-nonsuppressing TBI patients and ten normal control
      subjects matched for age, gender, and education. TBI subjects had highly
      significant bilateral hippocampal volume reductions, even when covaried for
      reductions in total brain volume. Degree of volume loss was not correlated with
      initial TBI severity. Findings support the hypothesis that hippocampal injury
      underlies P50 nonsuppression post TBI and suggest that such structural
      abnormalities may be observed even in "mildly" injured persons.

PMID- 11449029
TI  - In vivo evidence for differential association of striatal dopamine and midbrain
      serotonin systems with neuropsychiatric symptoms in Parkinson's disease.
AB  - Parkinson's disease affects various neurotransmitter systems. Using SPECT, the
      authors measured [(123)I]beta-CIT binding ratios of the caudate, putamen, medial
      thalamus, and dorsal midbrain over cerebellum in 16 patients with Parkinson's
      disease, and examined correlations with clinical ratings. Whereas striatal
      binding ratios (reflecting regional dopamine transporter densities) were
      associated with motor symptoms, dorsal midbrain binding ratios (reflecting
      regional serotonin transporter densities) were significantly correlated with the
      mentation, behavior, and mood subscale of the Unified Parkinson's Disease Rating
      Scale. These findings indicate that degeneration of the nigrostriatal
      dopaminergic neurons and a dysfunctional serotonergic raphe system contribute
      differentially to motor deficits and neuropsychiatric symptoms in Parkinson's
      disease.

PMID- 11449030
TI  - Validation of the Delirium Rating Scale-revised-98: comparison with the delirium
      rating scale and the cognitive test for delirium.
AB  - The DRS-R-98, a 16-item clinician-rated scale with 13 severity items and 3
      diagnostic items, was validated against the Cognitive Test for Delirium (CTD),
      Clinical Global Impression scale (CGI), and Delirium Rating Scale (DRS) among
      five diagnostic groups (N=68): delirium, dementia, depression, schizophrenia, and
      other. Mean and median DRS-R-98 scores significantly (P<0.001) distinguished
      delirium from each other group. DRS-R-98 total scores correlated highly with DRS,
      CTD, and CGI scores. Interrater reliability and internal consistency were very
      high. Cutoff scores for delirium are recommended based on ROC analyses
      (sensitivity and specificity ranges: total, 91%-100% and 85%-100%; severity, 86%
      100% and 77%-93%, respectively, depending on the cutoffs or comparison groups
      chosen). The DRS-R-98 is a valid measure of delirium severity over a broad range
      of symptoms and is a useful diagnostic and assessment tool. The DRS-R-98 is ideal
      for longitudinal studies.

PMID- 11449031
TI  - Presurgical postictal and acute interictal psychoses are differentially
      associated with postoperative mood and psychotic disorders.
AB  - The authors studied 52 patients who had undergone surgery because of intractable
      temporal lobe epilepsy. Investigation of postoperative psychiatric illnesses
      focused on psychotic disorder (293.81 and 293.82) and mood disorder (293.83) due
      to a general medical condition diagnosed according to DSM-IV criteria.
      Presurgically, two episodic psychotic syndromes, acute interictal and postictal
      psychosis, were defined operationally. A correlation was confirmed between
      presurgical acute interictal psychosis and postsurgical psychotic disorder, as
      well as between presurgical postictal psychosis and postsurgical mood disorder.
      An excellent final outcome for postoperative mood disorder in contrast to a less
      favorable one for psychotic disorder was also suggested.

PMID- 11449032
TI  - Methylphenidate improves HIV-1-associated cognitive slowing.
AB  - Sixteen HIV-1 seropositive individuals participated in a single-blind, placebo
      controlled, crossover-design study of the effectiveness of 30 mg/ day of
      methylphenidate (MPH) in the treatment of HIV-associated cognitive slowing.
      Regression analyses revealed that participants who entered the study with a
      greater degree of either depressive symptomatology or cognitive slowing tended to
      demonstrate a better response to MPH on computerized measures of choice and dual
      task reaction time. Participants without evidence of cognitive slowing at study
      entry did not show greater improvement on MPH than on placebo. Contrary to
      expectation, symptoms of depression did not respond better to MPH than to
      placebo, regardless of initial symptomatology. Information processing slowing in
      HIV-1 infection therefore appears amenable to pharmacologic intervention with the
      dopamine agonist MPH. However, results suggest clinicians should consider
      reserving the use of MPH for patients with more pronounced cognitive and
      affective deficits.

PMID- 11449033
TI  - Specific frontal lobe subregions correlated with unawareness of illness in
      schizophrenia: a preliminary study.
AB  - The authors examined the relationship between unawareness of illness and eight
      frontal lobe subregions in 15 patients with schizophrenia. Significant inverse
      correlations were seen between unawareness and bilateral middle frontal gyrus
      volume and between symptom misattribution and superior frontal gyrus volume.

PMID- 11449034
TI  - Dentatorubral-pallidoluysian atrophy (DRPLA) presenting with psychosis.
AB  - The authors report on four DRPLA patients who manifested delusions. All patients
      demonstrated autosomal dominant DRPLA confirmed by standard gene analysis.
      Patients with DRPLA can exhibit a variety of psychiatric symptoms in addition to
      extrapyramidal and cerebellar symptoms.

PMID- 11449035
TI  - Neuropsychiatric significance of subcortical hyperintensity.

PMID- 11449037
TI  - Psychotherapy and the single synapse: the impact of psychiatric thought on
      neurobiological research. 1979.

PMID- 11449038
TI  - Clonic seizure associated with high clozapine plasma level.

PMID- 11449039
TI  - Cognitive and neuropsychiatric side effects of mefloquine.

PMID- 11449040
TI  - Intravenous valproic acid in the treatment of severe catatonia.

PMID- 11449041
TI  - 5-Lipoxygenase (5-LOX) promoter polymorphism in patients with early-onset and
      late-onset Alzheimer's disease.

PMID- 11449042
TI  - Celecoxib- and rofecoxib-induced delirium.

PMID- 11449044
TI  - Move it on out with MATEs.

PMID- 11449045
TI  - APO2001: A sexy apomixer in como.

PMID- 11449046
TI  - How to avoid sex: the genetic control of gametophytic apomixis.

PMID- 11449047
TI  - Growth stage-based phenotypic analysis of Arabidopsis: a model for high
      throughput functional genomics in plants.
AB  - With the completion of the Arabidopsis genome sequencing project, the next major
      challenge is the large-scale determination of gene function. As a model organism
      for agricultural biotechnology, Arabidopsis presents the opportunity to provide
      key insights into the way that gene function can affect commercial crop
      production. In an attempt to aid in the rapid discovery of gene function, we have
      established a high throughput phenotypic analysis process based on a series of
      defined growth stages that serve both as developmental landmarks and as triggers
      for the collection of morphological data. The data collection process has been
      divided into two complementary platforms to ensure the capture of detailed data
      describing Arabidopsis growth and development over the entire life of the plant.
      The first platform characterizes early seedling growth on vertical plates for a
      period of 2 weeks. The second platform consists of an extensive set of
      measurements from plants grown on soil for a period of approximately 2 months.
      When combined with parallel processes for metabolic and gene expression
      profiling, these platforms constitute a core technology in the high throughput
      determination of gene function. We present here analyses of the development of
      wild-type Columbia (Col-0) plants and selected mutants to illustrate a framework
      methodology that can be used to identify and interpret phenotypic differences in
      plants resulting from genetic variation and/or environmental stress.

PMID- 11449048
TI  - A new dynamin-like protein, ADL6, is involved in trafficking from the trans-Golgi
      network to the central vacuole in Arabidopsis.
AB  - Dynamin, a high-molecular-weight GTPase, plays a critical role in vesicle
      formation at the plasma membrane during endocytosis in animal cells. Here we
      report the identification of a new dynamin homolog in Arabidopsis named
      Arabidopsis dynamin-like 6 (ADL6). ADL6 is quite similar to dynamin I in its
      structural organization: a conserved GTPase domain at the N terminus, a
      pleckstrin homology domain at the center, and a Pro-rich motif at the C terminus.
      In the cell, a majority of ADL6 is associated with membranes.
      Immunohistochemistry and in vivo targeting experiments revealed that ADL6 is
      localized to the Golgi apparatus. Expression of the dominant negative mutant
      ADL6[K51E] in Arabidopsis protoplasts inhibited trafficking of cargo proteins
      destined for the lytic vacuole and caused them to accumulate at the trans-Golgi
      network. In contrast, expression of ADL6[K51E] did not affect trafficking of a
      cargo protein, H(+)-ATPase:green fluorescent protein, destined for the plasma
      membrane. These results suggest that ADL6 is involved in vesicle formation for
      vacuolar trafficking at the trans-Golgi network but not for trafficking to the
      plasma membrane in plant cells.

PMID- 11449049
TI  - Evidence for an important role of WRKY DNA binding proteins in the regulation of
      NPR1 gene expression.
AB  - The Arabidopsis NPR1 gene is a positive regulator of inducible plant disease
      resistance. Expression of NPR1 is induced by pathogen infection or treatment with
      defense-inducing compounds such as salicylic acid (SA). Transgenic plants
      overexpressing NPR1 exhibit enhanced resistance to a broad spectrum of microbial
      pathogens, whereas plants underexpressing the gene are more susceptible to
      pathogen infection. These results suggest that regulation of NPR1 gene expression
      is important for the activation of plant defense responses. In the present study,
      we report the identification of W-box sequences in the promoter region of the
      NPR1 gene that are recognized specifically by SA-induced WRKY DNA binding
      proteins from Arabidopsis. Mutations in these W-box sequences abolished their
      recognition by WRKY DNA binding proteins, rendered the promoter unable to
      activate a downstream reporter gene, and compromised the ability of NPR1 to
      complement npr1 mutants for SA-induced defense gene expression and disease
      resistance. These results provide strong evidence that certain WRKY genes act
      upstream of NPR1 and positively regulate its expression during the activation of
      plant defense responses. Consistent with this model, we found that SA-induced
      expression of a number of WRKY genes was independent of NPR1.

PMID- 11449050
TI  - One plant actin isovariant, ACT7, is induced by auxin and required for normal
      callus formation.
AB  - During plant growth and development, the phytohormone auxin induces a wide array
      of changes that include cell division, cell expansion, cell differentiation, and
      organ initiation. It has been suggested that the actin cytoskeleton plays an
      active role in the elaboration of these responses by directing specific changes
      in cell morphology and cytoarchitecture. Here we demonstrate that the promoter
      and the protein product of one of the Arabidopsis vegetative actin genes, ACT7,
      are rapidly and strongly induced in response to exogenous auxin in the cultured
      tissues of Arabidopsis. Homozygous act7-1 mutant plants were slow to produce
      callus tissue in response to hormones, and the mutant callus contained at least
      two to three times lower levels of ACT7 protein than did the wild-type callus. On
      the other hand, a null mutation in ACT2, another vegetative actin gene, did not
      significantly affect callus formation from leaf or root tissue. Complementation
      of the act7-1 mutants with the ACT7 genomic sequence restored their ability to
      produce callus at rates similar to those of wild-type plants, confirming that the
      ACT7 gene is required for callus formation. Immunolabeling of callus tissue with
      actin subclass-specific antibodies revealed that the predominant ACT7 is
      coexpressed with the other actin proteins. We suggest that the coexpression, and
      probably the copolymerization, of the abundant ACT7 with the other actin
      isovariants in cultured cells may facilitate isovariant dynamics well suited for
      cellular responses to external stimuli such as hormones.

PMID- 11449051
TI  - Repressing a repressor: gibberellin-induced rapid reduction of the RGA protein in
      Arabidopsis.
AB  - RGA (for repressor of ga1-3) and SPINDLY (SPY) are likely repressors of
      gibberellin (GA) signaling in Arabidopsis because the recessive rga and spy
      mutations partially suppressed the phenotype of the GA-deficient mutant ga1-3. We
      found that neither rga nor spy altered the GA levels in the wild-type or the ga1
      3 background. However, expression of the GA biosynthetic gene GA4 was reduced 26%
      by the rga mutation, suggesting that partial derepression of the GA response
      pathway by rga resulted in the feedback inhibition of GA4 expression. The green
      fluorescent protein (GFP)-RGA fusion protein was localized to nuclei in
      transgenic Arabidopsis. This result supports the predicted function of RGA as a
      transcriptional regulator based on sequence analysis. Confocal microscopy and
      immunoblot analyses demonstrated that the levels of both the GFP-RGA fusion
      protein and endogenous RGA were reduced rapidly by GA treatment. Therefore, the
      GA signal appears to derepress the GA signaling pathway by degrading the
      repressor protein RGA. The effect of rga on GA4 gene expression and the effect of
      GA on RGA protein level allow us to identify part of the mechanism by which GA
      homeostasis is achieved.

PMID- 11449052
TI  - The last step of syringyl monolignol biosynthesis in angiosperms is regulated by
      a novel gene encoding sinapyl alcohol dehydrogenase.
AB  - Cinnamyl alcohol dehydrogenase (CAD; EC 1.1.1.195) has been thought to mediate
      the reduction of both coniferaldehyde and sinapaldehyde into guaiacyl and
      syringyl monolignols in angiosperms. Here, we report the isolation of a novel
      aspen gene (PtSAD) encoding sinapyl alcohol dehydrogenase (SAD), which is
      phylogenetically distinct from aspen CAD (PtCAD). Liquid chromatography-mass
      spectrometry-based enzyme functional analysis and substrate level-controlled
      enzyme kinetics consistently demonstrated that PtSAD is sinapaldehyde specific
      and that PtCAD is coniferaldehyde specific. The enzymatic efficiency of PtSAD for
      sinapaldehyde was approximately 60 times greater than that of PtCAD. These data
      suggest that in addition to CAD, discrete SAD function is essential to the
      biosynthesis of syringyl monolignol in angiosperms. In aspen stem primary
      tissues, PtCAD was immunolocalized exclusively to xylem elements in which only
      guaiacyl lignin was deposited, whereas PtSAD was abundant in syringyl lignin
      enriched phloem fiber cells. In the developing secondary stem xylem, PtCAD was
      most conspicuous in guaiacyl lignin-enriched vessels, but PtSAD was nearly absent
      from these elements and was conspicuous in fiber cells. In the context of
      additional protein immunolocalization and lignin histochemistry, these results
      suggest that the distinct CAD and SAD functions are linked spatiotemporally to
      the differential biosynthesis of guaiacyl and syringyl lignins in different cell
      types. SAD is required for the biosynthesis of syringyl lignin in angiosperms.

PMID- 11449053
TI  - Somatic and germinal mobility of the RescueMu transposon in transgenic maize.
AB  - RescueMu, a Mu1 element containing a bacterial plasmid, is mobilized by MuDR in
      transgenic maize. Somatic excision from a cell-autonomous marker gene yields >90%
      single cell sectors; empty donor sites often have deletions and insertions,
      including up to 210 bp of RescueMu/Mu1 terminal DNA. Late somatic insertions are
      contemporaneous with excisions, suggesting that "cut-and-paste" transposition
      occurs in the soma. During reproduction, RescueMu transposes infrequently from
      the initial transgene array, but once transposed, RescueMu is suitable for high
      throughput gene mutation and cloning. As with MuDR/Mu elements, heritable
      RescueMu insertions are not associated with excisions. Both somatic and germinal
      RescueMu insertions occur preferentially into genes and gene-like sequences, but
      they exhibit weak target site preferences. New insights into Mu behaviors are
      discussed with reference to two models proposed to explain the alternative
      outcomes of somatic and germinal events: a switch from somatic cut-and-paste to
      germinal replicative transposition or to host-mediated gap repair from sister
      chromatids.

PMID- 11449054
TI  - A gene related to yeast HOS2 histone deacetylase affects extracellular
      depolymerase expression and virulence in a plant pathogenic fungus.
AB  - A gene, HDC1, related to the Saccharomyces cerevisiae histone deacetylase (HDAC)
      gene HOS2, was isolated from the filamentous fungus Cochliobolus carbonum, a
      pathogen of maize that makes the HDAC inhibitor HC-toxin. Engineered mutants of
      HDC1 had smaller and less septate conidia and exhibited an approximately 50%
      reduction in total HDAC activity. Mutants were strongly reduced in virulence as a
      result of reduced penetration efficiency. Growth of hdc1 mutants in vitro was
      normal on glucose, slightly decreased on sucrose, and reduced by 30 to 73% on
      other simple and complex carbohydrates. Extracellular depolymerase activities and
      expression of the corresponding genes were downregulated in hdc1 mutant strains.
      Except for altered conidial morphology, the phenotypes of hdc1 mutants were
      similar to those of C. carbonum strains mutated in ccSNF1 encoding a protein
      kinase necessary for expression of glucose-repressed genes. These results show
      that HDC1 has multiple functions in a filamentous fungus and is required for full
      virulence of C. carbonum on maize.

PMID- 11449055
TI  - Arabidopsis ALF5, a multidrug efflux transporter gene family member, confers
      resistance to toxins.
AB  - The Arabidopsis genome contains many gene families that are not found in the
      animal kingdom. One of these is the multidrug and toxic compound extrusion (MATE)
      family, which has homology with bacterial efflux transporters. Arabidopsis has at
      least 54 members of this family, which often are found in tandem repeats.
      Analysis of ALF5, one member of this Arabidopsis family, suggests that its
      function is required for protection of the roots from inhibitory compounds. Loss
      of ALF5 function results in the sensitivity of the root to a number of compounds,
      including a contaminant of commercial agar. Moreover, expression of the
      Arabidopsis ALF5 cDNA in yeast confers resistance to tetramethylammonium. These
      phenotypes are consistent with a role for ALF5 as an efflux transporter. Both
      transcriptional and translational fusions of ALF5 to the beta-glucuronidase
      reporter gene show that ALF5 is expressed strongly in the root epidermis, a
      tissue in direct contact with the external environment. The distinct requirement
      for ALF5 function is remarkable because of the large number of MATE gene family
      members in Arabidopsis, one of which is adjacent to ALF5 and 83% identical to
      ALF5 at the amino acid level.

PMID- 11449056
TI  - Overexpression of the heterotrimeric G-protein alpha-subunit enhances phytochrome
      mediated inhibition of hypocotyl elongation in Arabidopsis.
AB  - Plant heterotrimeric G-proteins have been implicated in a number of signaling
      processes. However, most of these studies are based on biochemical or
      pharmacological approaches. To examine the role of heterotrimeric G-proteins in
      plant development, we generated transgenic Arabidopsis expressing the Galpha
      subunit of the heterotrimeric G-protein under the control of a glucocorticoid
      inducible promoter. With the conditional overexpression of either the wild type
      or a constitutively active version of Arabidopsis Galpha, transgenic seedlings
      exhibited a hypersensitive response to light. This enhanced light sensitivity was
      more exaggerated in a relatively lower intensity of light and was observed in
      white light as well as far-red, red, and blue light conditions. The enhanced
      responses in far-red and red light required functional phytochrome A and
      phytochrome B, respectively. Furthermore, the response to far-red light depended
      on functional FHY1 but not on FIN219 and FHY3. This dependence on FHY1 indicates
      that the Arabidopsis Galpha protein may act only on a discrete branch of the
      phytochrome A signaling pathway. Thus, our results support the involvement of a
      heterotrimeric G-protein in the light regulation of Arabidopsis seedling
      development.

PMID- 11449057
TI  - Functional analysis of cyclin-dependent kinase inhibitors of Arabidopsis.
AB  - Cyclin-dependent kinase inhibitors, such as the mammalian p27(Kip1) protein,
      regulate correct cell cycle progression and the integration of developmental
      signals with the core cell cycle machinery. These inhibitors have been described
      in plants, but their function remains unresolved. We have isolated seven genes
      from Arabidopsis that encode proteins with distant sequence homology with
      p27(Kip1), designated Kip-related proteins (KRPs). The KRPs were characterized by
      their domain organization and transcript profiles. With the exception of KRP5,
      all presented the same cyclin-dependent kinase binding specificity. When
      overproduced, KRP2 dramatically inhibited cell cycle progression in leaf
      primordia cells without affecting the temporal pattern of cell division and
      differentiation. Mature transgenic leaves were serrated and consisted of enlarged
      cells. Although the ploidy levels in young leaves were unaffected,
      endoreduplication was suppressed in older leaves. We conclude that KRP2 exerts a
      plant growth inhibitory activity by reducing cell proliferation in leaves, but,
      in contrast to its mammalian counterparts, it may not control the timing of cell
      cycle exit and differentiation.

PMID- 11449058
TI  - Rerouting the plant phenylpropanoid pathway by expression of a novel bacterial
      enoyl-CoA hydratase/lyase enzyme function.
AB  - The gene for a bacterial enoyl-CoA hydratase (crotonase) homolog (HCHL)
      previously shown to convert 4-coumaroyl-CoA, caffeoyl-CoA, and feruloyl-CoA to
      the corresponding hydroxybenzaldehydes in vitro provided an opportunity to
      subvert the plant phenylpropanoid pathway and channel carbon flux through 4
      hydroxybenzaldehyde and the important flavor compound 4-hydroxy-3
      methoxybenzaldehyde (vanillin). Expression of the Pseudomonas fluorescens AN103
      HCHL gene in two generations of tobacco plants caused the development of
      phenotypic abnormalities, including stunting, interveinal chlorosis and
      senescence, curled leaf margins, low pollen production, and male sterility. In
      second generation progeny, the phenotype segregated with the transgene and
      transgenic siblings exhibited orange/red coloration of the vascular ring,
      distorted cells in the xylem and phloem bundles, and lignin
      modification/reduction. There was depletion of the principal phenolics
      concomitant with massive accumulation of novel metabolites, including the
      glucosides and glucose esters of 4-hydroxybenzoic acid and vanillic acid and the
      glucosides of 4-hydroxybenzyl alcohol and vanillyl alcohol. HCHL plants exhibited
      increased accumulation of transcripts for phenylalanine ammonia-lyase, cinnamate
      4-hydroxylase, and 4-coumarate:CoA ligase, whereas beta-1,3-glucanase was
      suppressed. This study, exploiting the ability of a bacterial gene to divert
      plant secondary metabolism, provides insight into how plants modify
      inappropriately accumulated metabolites and reveals the consequences of depleting
      the major phenolic pools.

PMID- 11449059
TI  - Genetic and chemical reductions in protein phosphatase activity alter auxin
      transport, gravity response, and lateral root growth.
AB  - Auxin transport is required for important growth and developmental processes in
      plants, including gravity response and lateral root growth. Several lines of
      evidence suggest that reversible protein phosphorylation regulates auxin
      transport. Arabidopsis rcn1 mutant seedlings exhibit reduced protein phosphatase
      2A activity and defects in differential cell elongation. Here we report that
      reduced phosphatase activity alters auxin transport and dependent physiological
      processes in the seedling root. Root basipetal transport was increased in rcn1 or
      phosphatase inhibitor-treated seedlings but showed normal sensitivity to the
      auxin transport inhibitor naphthylphthalamic acid (NPA). Phosphatase inhibition
      reduced root gravity response and delayed the establishment of differential auxin
      induced gene expression across a gravity-stimulated root tip. An NPA treatment
      that reduced basipetal transport in rcn1 and cantharidin-treated wild-type plants
      also restored a normal gravity response and asymmetric auxin-induced gene
      expression, indicating that increased basipetal auxin transport impedes
      gravitropism. Increased auxin transport in rcn1 or phosphatase inhibitor-treated
      seedlings did not require the AGR1/EIR1/PIN2/WAV6 or AUX1 gene products. In
      contrast to basipetal transport, root acropetal transport was normal in
      phosphatase-inhibited seedlings in the absence of NPA, although it showed reduced
      NPA sensitivity. Lateral root growth also exhibited reduced NPA sensitivity in
      rcn1 seedlings, consistent with acropetal transport controlling lateral root
      growth. These results support the role of protein phosphorylation in regulating
      auxin transport and suggest that the acropetal and basipetal auxin transport
      streams are differentially regulated.

PMID- 11449064
TI  - Graft-Versus-Host Alloresponses to Treat Nonlymphohematopoietic Tumors: Is There
      a Solid Approach?

PMID- 11449063
TI  - Tumor-Dendritic Cell Fusion Technology and Immunotherapy Strategies.

PMID- 11449065
TI  - Issues on Clinical Applications of Cancer Vaccines.

PMID- 11449066
TI  - Antitumor Effect of Immunizations With Fusions of Dendritic and Glioma Cells in a
      Mouse Brain Tumor Model.
AB  - SUMMARY: The authors studied antitumor immunity conferred by fusions of dendritic
      and glioma cells in a mouse brain tumor model. Previous immunization with fusion
      cells (FCs) prevented tumor formation on challenge with glioma cells in the flank
      or in the brain. Efficacy was decreased when studies were performed in mice
      depleted of CD8+ cells. In a treatment model, FCs were injected subcutaneously
      after tumor development in the brain. The administration of FCs alone had limited
      effects on survival of mice bearing brain tumors. Importantly, however,
      administration of FCs and recombinant interleukin-12 (rIL-12) remarkably
      prolonged the survival of mice with brain tumors. Cytotoxic T lymphocyte activity
      against glioma cells from immunized mice was also stimulated by coadministration
      of FCs and rIL-12 compared with that obtained with FCs or rIL-12 alone. These
      data support the therapeutic efficacy of combining FC-based vaccine therapy and
      rIL-12.

PMID- 11449067
TI  - Cell Therapy With Preimmunized Effector Cells Mismatched for Minor
      Histocompatible Antigens in the Treatment of a Murine Mammary Carcinoma.
AB  - SUMMARY: Cell therapy with allogeneic donor cells mismatched for minor
      histocompatible (MiHC) antigens was applied to a murine mammary carcinoma (4T1)
      model to test the feasibility of graft versus tumor (GVT) effect against
      metastatic epithelial tumor cells. BALB/c mice bearing a 4T1 tumor of BALB/c
      origin were given syngeneic or MiHC-mismatched splenocytes. GVT effects were
      determined in secondary recipients of adoptively transferred lung cells derived
      from primary hosts who had previously been inoculated intravenously with 4T1
      cells, and injected with one of the following: 1) naive BALB/c splenocytes, 2)
      naive DBA/2 splenocytes, 3) 4T1-immune DBA/2 splenocytes, or 4) DBA/2 splenocytes
      immunized with host-derived BABL/c spleen cells. Naive DBA/2 splenocytes
      inhibited tumor growth only slightly and only slightly prolonged the survival of
      secondary recipients, in comparison with fully matched tumor/host BALB/c spleen
      cells. An efficient GVT reaction was demonstrated in vitro and in vivo with MiHC
      mismatched DBA/2 splenocytes from mice presensitized by multiple injections of
      irradiated tumor or BALB/c-derived spleen cells. All 30 mice adoptively
      inoculated with lung cells from primary hosts that had previously been treated
      with these presensitized effector cells were tumor free for >250 days. Secondary
      recipients inoculated with lung cells from mice given naive BALB/c or DBA/2
      spleen cells died of metastatic tumors within 33 to 46 days. These results
      suggest that preimmunized donor cells represent an effective tool against
      metastatic disease; hence, the next goal should be to control graft-versus-host
      disease while exploiting the GVT potential.

PMID- 11449068
TI  - A Rapid, Novel Strategy to Induce Tumor Cell-Specific Cytotoxic T Lymphocyte
      Responses Using Instant Dendritomas.
AB  - SUMMARY: The generation of fused cells between dendritic cells (DC) and tumor
      cells is a very effective approach for tumor antigen presentation in cancer
      immunotherapy. However, the application of this approach in clinical studies is
      limited by the need for established tumor cell lines and the time-consuming
      procedures for selecting and expanding the fused cells. In the current study, the
      authors report a rapid, novel approach to produce fused cells between DCs and
      primary tumor cells from patients with malignant melanoma. Peripheral blood DCs
      and a primary tumor cell culture were generated from the same patients, labeled
      with fluorescent green and red dyes, respectively, and fused. The fused cells
      were isolated by fluorescence-activated cell sorting. Because the fused cells do
      not need to be expanded, these cell hybrids have been named instant dendritomas.
      Fluorescence-activated cell sorting analysis showed that instant dendritomas
      express the key molecules for antigen presentation (HLA-A, B, C; HLA-DR; CD80;
      and CD86). In vitro studies have shown that instant dendritomas effectively
      activated autologous CD8+ T lymphocytes to proliferate and secret interferon
      gamma. More importantly, the activated CD8+ T lymphocytes effectively lysed the
      patients' primary tumor cells. This approach represents a practical clinical
      strategy for cancer immunotherapy.

PMID- 11449069
TI  - Dendritic Cell Infiltration in Colon Cancer.
AB  - We quantitatively evaluated dendritic cell (DC) infiltration in primary
      colorectal cancers from 44 patients and metastatic colorectal tumors from 13
      patients using immunohistochemistry for the DC marker CD83, HLA-DR, and the DC
      activation molecules CD40 and CD86. Nearly all CD83+ cells were also HLA-DR+,
      CD40+, and CD86+, indicating that the DCs that infiltrate colon cancer in vivo
      express the activation and costimulatory molecules associated with a mature DC
      phenotype. The density of DCs in colorectal cancer primaries was three times
      lower than that seen in normal colonic mucosa (0.29 versus 0.84 CD83+ cells/ high
      power field (hpf), p < 0.001). Dendritic cells were rarely observed in metastatic
      tumors: DC density in metastases was sixfold lower than in colorectal primary
      tumors (0.05 versus 0.29 CD83+ cells/hpf, p < 0.001). Because cytokines have been
      shown, in vitro, to exert potent effects on DCs, we also evaluated the
      relationship between intratumor DC density and the expression of cytokines by
      tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression of interleukin
      10 and transforming growth factor beta by either TIL or tumor cells was not
      associated with decreased DC density or decreased expression of CD40 or CD86 on
      DCs. Tumor expression of vascular endothelial growth factor was associated with a
      more than twofold increase in DC density (p = 0.01). Patients who had a high
      proportion of TILs expressing tumor necrosis factor (TNF) had a greater
      intratumor mature DC density than patients with a low proportion of TNF + TIL
      (0.54 versus 0.21 CD83+ cells/hpf, p < 0.01).

PMID- 11449070
TI  - Expression of the Chemokines IP-10 and Mig in IL-10 Transduced Tumors.
AB  - SUMMARY: Several laboratories have reported marked tumor inhibition when the
      cytokine interleukin-10 (IL-10) is overexpressed as a transgene in a variety of
      tumor cells. To identify critical effector molecules, we compared the expression
      of the chemokine crg-2, the murine homolog of human inducible protein 10 (human
      IP-10) in murine mammary tumors derived from the transplantation of six IL-10
      expressing clones of tumor cell line 66.1, parental 66.1, or 66-neo-cells. We
      observed increased levels of IP-10 mRNA in all IL-10-expressing tumors examined
      in comparison to 66-neo. IP-10 mRNA was not detected in parental 66.1 tumors. The
      closely related chemokine Mig (monokine induced by interferon-gamma [IFN-gamma])
      was also induced in all IL-10-expressing tumors. Studies of cultured tumor cells
      in vitro show that mammary epithelial tumor cells, in the absence of host
      elements, can express IP-10 and Mig in response to induction with either
      lipopolysaccharide (LPS) or IFN-gamma alone. The combination of LPS plus IFN
      gamma resulted in even greater induction of IP-10 RNA. The kinetics of induction
      differ somewhat for the two chemokines, with IP-10 showing slower induction and
      less rapid decline. Because both Mig and IP-10 are chemotactic for tumor
      infiltrating lymphocytes, we examined the presence of CD4+ and CD8+ lymphocytes
      in these tumors. Consistent with the upregulation of Mig and IP-10, we saw
      significantly increased numbers of CD8+ cells and a lesser increase in CD4+ cells
      in tumors with elevated levels of both chemokines.

PMID- 11449071
TI  - Cytotoxicity of Antiosteosarcoma Recombinant Immunotoxins Composed of TP-3 Fv
      Fragments and a Truncated Pseudomonas Exotoxin A.
AB  - SUMMARY: Regrowth of drug-resistant tumor cells is responsible for approximately
      half of an unselected osteosarcoma population still dying of the disease despite
      aggressive combination therapy. Two monoclonal antibodies, TP-1 (immunoglobulin
      2a) and TP-3 (immunoglobulin 2b) are available, which specifically recognize an
      antigen on osteosarcoma cells. In this work, we have fused the variable (V) genes
      of TP-3 to a truncated fragment of Pseudomonas exotoxin A, referred to as PE38.
      Two immunotoxins were made that differed in the Fv portion: TP-3(scFv)-PE38,
      which contains a peptide linker, and TP-3(dsFv)-PE38, which contains a disulfide
      bond for stabilization of the association between the V domains. Recombinant TP-3
      immunotoxins were expressed in Escherichia coli and purified from inclusion
      bodies. We describe the design and expression of these immunotoxins, and their
      properties with regard to antigen binding, stability, and cytotoxicity. Toxicity
      studies were done in mice. We found that the immunotoxins exhibited very similar
      in vitro properties, whereas in vivo TP-3(dsFv)-PE38 was much better tolerated
      than TP-3(scFv)-PE38.

PMID- 11449073
TI  - Proinflammatory Cytokines and CD40 Ligand Enhance Cross-Presentation and Cross
      Priming Capability of Human Dendritic Cells Internalizing Apoptotic Cancer Cells.
AB  - SUMMARY: Human monocyte-derived dendritic cells (DC) can ingest apoptotic tumor
      cells (ATC) and present tumor-associated antigens (TAA) to T cells, leading to
      the generation of tumor-specific cytotoxic effector cells (Cancer Res
      2000;60:3542-9). To further augment antitumor effector cell responses, attempts
      were made to modify antigen presentation and cross-priming of T cells by DC fed
      with ATC. Proinflammatory cytokines (PC), CD40 ligand (CD40L) and/or interferon
      gamma (IFN-gamma) were found to markedly enhance the immunogenicity of TAA
      presented by DC. While PC upregulated expression of major histocompatibility
      complex class I/II and costimulatory molecules on the surface of DC, CD40L +/-
      IFN-gamma increased interleukin (IL)-12 and to a lesser extent, IL-15 production
      by DC. Additionally, lactacystin, a specific proteasome inhibitor, significantly
      abrogated the effects of IFN-gamma and, in part, also those of CD40L or PC. The
      ability of DC + ATC to cross-prime TAA-inexperienced ("naive") T cells was
      significantly enhanced by PC and CD40L or CD40L + IFN-gamma, but not by IFN-gamma
      alone. These results indicate that future vaccines for patients with cancer
      incorporating DC fed with ATC could be made more effective by the addition of
      proinflammatory cytokines or CD40L +/- IFN-gamma to improve the DC function.

PMID- 11449074
TI  - Mannan Mucin-1 Peptide Immunization: Influence of Cyclophosphamide and the Route
      of Injection.
AB  - SUMMARY: The mucin MUC1 is greatly increased in breast cancer and is a potential
      target for immunotherapy. In mice, MUC1 conjugated to oxidized mannan (MUC1
      mannan fusion protein [M-FP]) targets the mannose receptor and induces a high
      frequency of cytotoxic T lymphocytes and anti-tumor responses. On this basis,
      three phase I trials were performed in patients with adenocarcinoma to evaluate
      the tnxicity and the immunologic responses to mannan MUC1. Forty-one patients
      with metastatic or locally advanced carcinoma of the breast (trial 1), colon
      (trial 2), and various adenocarcinomas (trial 3) received increasing doses of M
      FP (1 to 300 &mgr;g). The immunizations were given at weekly intervals (weeks 1
      to 3) and repeated in weeks 7 to 9. Cyclophosphamide (to increase cellular
      immunity) was given on weeks 1 and 4. M-FP was given intramuscularly in trial 1
      and intraperitoneally in trial 2. No toxic effects occurred, and delayed-type
      hypersensitivity responses were present only as a microscopic lymphocytic
      infiltration. Overall, approximately 60% of the patients had high-titer MUC1
      immunoglobulin G1 antibody responses, with the intraperitoneal route yielding
      approximately 10-fold higher responses. Cellular responses (proliferation,
      cytotoxic T cells, or CD8 T cells secreting tumor necrosis factor-alpha alphand
      interferon-gamma in response to MUC1 stimulation in vitro) were found in 28% of
      the patients, which was similar to that seen without cyclophosphamide. In most
      patients, disease progressed, but in five it remained stable. In addition, there
      were no objective responses. M-FP is not toxic and induces immune responses that
      were amplified by the intraperitoneal route of immunization. Cyclophosphamide was
      of no benefit.

PMID- 11449075
TI  - Neoadiuvant Treatment With Intravesical Interleukin-2 for Recurrent Superficial
      Transitional Bladder Carcinoma Ta-T1/G1-2.
AB  - SUMMARY: The aim of this study was to evaluate the direct action of IL-2 on
      recurrent superficial transitional bladder carcinoma and the effect on recurrence
      rate. 27 patients were submitted to neoadjuvant treatment by intra-vesical
      instillation of recombinant IL-2 and to transurethral resection. We did not
      observe any effect on neoplasms but the recurrence rate was less than the
      expected one. It is possible that treatment of bladder carcinoma with intra
      vesical instillation of IL-2 may promote immuno-prophilaxis.

PMID- 11449076
TI  - A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the
      Effect of Nystatin on the Development of Oral Irritation in Patients Receiving
      High-Dose Intravenous Interleukin-2.
AB  - SUMMARY: Interleukin-2 (IL-2) has been used to treat patients with metastatic
      melanoma and renal cell cancer for nearly two decades, and much progress has been
      made in ameliorating its adverse effects. One bothersome adverse effect, oral
      pain or oral irritation, is usually treated with an oral antifungal antibiotic,
      nystatin. The authors performed a prospective, randomized, double-blind, placebo
      controlled trial involving 64 patients to evaluate the effect of prophylactic
      administration of nystatin or placebo on the development of oral irritation in
      patients receiving high-dose intravenous IL-2. No difference was found between
      patients randomized to receive nystatin or placebo in their rates of development
      of oral irritation, the severity of IL-2 adverse effects, the duration of their
      treatment, the rate of development of positive studies for oral yeast, or their
      pattern of experiencing other adverse effects. Thus, patients who receive high
      dose intravenous IL-2 should not be treated prophylactically with nystatin to
      prevent oral irritation, and clinicians should seek evidence of the presence of
      oral thrush before using antifungal agents to treat oral pain in these patients.

PMID- 11449077
TI  - Androgens and syndrome X.

PMID- 11449078
TI  - Menopause and weight.

PMID- 11449079
TI  - Esterified estrogens combined with methyltestosterone improve emotional well
      being in postmenopausal women with chest pain and normal coronary angiograms.
AB  - OBJECTIVE: The cardiac syndrome X is described as the triad of angina pectoris, a
      positive exercise test for myocardial ischemia, and angiographically smooth
      coronary arteries. Although syndrome X does not result in an increased risk of
      cardiovascular mortality, the symptoms are often troublesome and unresponsive to
      conventional antianginal therapy. The majority of patients are postmenopausal,
      and estrogen therapy can alleviate anginal symptoms. We investigated the effect
      of esterified estrogens combined with methyltestosterone (Estratest) on quality
      of life in postmenopausal women with syndrome X. DESIGN: Patients were withdrawn
      from antianginal therapy. Sublingual nitrates were allowed for treatment of
      anginal episodes. Patients underwent treadmill testing, and quality of life was
      assessed by using the Short Form-36 and Cardiac Health Profile questionnaires
      after the women had received 8 weeks of Estratest or identical placebo in a
      randomized, double-blind, cross-over study. RESULTS: Nineteen patients were
      randomized, and 16 patients completed the protocol. Plasma 17beta-estradiol
      concentrations were significantly increased by Estratest; however, total
      testosterone levels were not. The "emotional" score of the Cardiac Health Profile
      questionnaire was significantly improved after Estratest use compared with
      placebo (p = 0.03); however, there was no significant change in the Short Form-36
      questionnaire for any variable. Estratest significantly increased systolic blood
      pressure and rate pressure product at rest but had no effect on exercise
      parameters. Time to onset of chest pain during exercise was also unaffected.
      CONCLUSIONS: We have demonstrated a beneficial effect of Estratest on emotional
      well-being in postmenopausal women with cardiological syndrome X. There was no
      significant treatment effect on exercise parameters, including time to onset of
      chest pain.

PMID- 11449080
TI  - Changes in body mass index around menopause: a population study of Chilean woman.
AB  - OBJECTIVE: To evaluate the influence of menopause and hormone replacement therapy
      (HRT) on weight and the effect of weight gain on coronary risk factors. DESIGN:
      From 1991 to 1992 cardiovascular risk factors were assessed in 271 premenopausal
      women between the ages of 40 and 53 years. The women were not receiving HRT at
      that time. Five years later, these women were reevaluated. RESULTS: Weight and
      body mass index (BMI) increased steadily with age. During the observation period
      there was an average increase of 4.0 kg +/- 4.6 (p < 0.0001). Women who
      experienced menopause and those who did not experience menopause had a similar
      weight increase (3.8 +/- 4.4 kg vs. 4.3 +/- 4.8, p = 0.37). Likewise, weight gain
      was similar in those who did or did not use HRT (nonusers, 4.3 +/- 4.6 kg; users,
      3.5 +/- 3.7 kg; ex-users, 3.4 +/- 5.8 kg). At their first checkups, overweight
      women and obese women already had significant differences in their risk factors,
      including higher systolic pressure (p < 0.02), diastolic pressure (p < 0.01),
      glucose (p < 0.02) and triglycerides (p < 0.0001), and lower high-density
      lipoprotein cholesterol (p < 0.004) as compared with women of normal weight.
      Unexpectedly, women of normal weight who became overweight or obese during the
      monitoring period did not show any deterioration in their risk factors.
      CONCLUSIONS: During the perimenopausal period there is a weight gain that does
      not seem to depend on the menopause or HRT. Being overweight or obese during the
      menopausal transition is not necessarily associated with deterioration in
      coronary risk factors. This seems to imply the existence of different metabolic
      populations within this group of women.

PMID- 11449081
TI  - The effect of the duration of progestin use on the occurrence of endometrial
      cancer in postmenopausal women.
AB  - OBJECTIVE: Women who have ever used estrogen replacement therapy (ERT), even at a
      low dose, have an increased incidence of endometrial cancer. The addition of a
      progestin to ERT reduces the incidence of endometrial cancer. The duration of
      progestin administration is more important than the dose. DESIGN: A MEDLINE
      review of the literature was performed using the search terms endometrial cancer,
      epidemiology, and hormone replacement therapy (HRT). RESULTS: Women who have ever
      used ERT have an increased incidence of endometrial cancer. The use of HRT for
      more than 5 years, with a progestin use of <10 days per cycle, has a relative
      risk = 1.8. Continuous combined HRT, or sequential or cyclic HRT with >10 days of
      progestin per cycle, appears to decrease the incidence of endometrial cancer to
      that found in nonusers of HRT. CONCLUSIONS: The use of HRT in postmenopausal
      women with a uterus reduces the incidence of endometrial cancer. The duration of
      progestin administration should be 14 days or more per cycle based on recent
      epidemiologic data.

PMID- 11449082
TI  - Continuous combined hormone replacement therapy with oral 17beta-estradiol and
      norethisterone acetate improves homocysteine metabolism in postmenopausal women.
AB  - OBJECTIVE: To evaluate the effect of a continuous combined oral hormone
      replacement therapy (HRT) on basal and post-methionine load homocysteine levels
      in postmenopausal women. DESIGN: Twenty-two postmenopausal women (PMW) were
      randomly allocated to receive either continuous combined oral HRT (2 mg of
      estradiol plus 1 mg of norethisterone acetate; n = 11) or no treatment (controls,
      n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed
      in each subject at time 0 and after 6 months. Serum homocysteine levels were
      measured by high-performance liquid chromatography in samples collected at time 0
      and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by
      high-performance liquid chromatography) and B12 and folate (both by ELISA) were
      assayed in samples collected at time 0. RESULTS: Serum levels of glucose and body
      mass index increased in treated PMW, whereas folate decreased in controls. In
      treated PMW, basal homocysteine tended to decrease (10.6 +/- 3.3 micromol/L vs.
      9.62 +/- 2.8 micromol/L, p = 0.062), whereas in controls it significantly
      increased (10.7 +/- 2.65 micromol/L vs. 12.17 +/- 3.89 micromol/L, p < 0.05).
      This increase was not significant after correction for vitamin status (p =
      0.072). Homocysteine values 4 h (31.9 +/- 13.53 micromol/L vs. 39.83 +/- 22.53
      micromol/L, p < 0.05) and 8 h (35.1 +/- 13.13 vs. 43.34 +/- 22.15 micromol/L)
      after methionine, and integrated homocysteine response to methionine (392.5 +/-
      133.8 micromol/24 h vs. 458.8 +/- 104.8 micromol/24 h; p < 0.05), were
      significantly reduced in HRT-treated, but not in untreated, PMW. CONCLUSIONS:
      Continuous combined oral HRT with17beta-estradiol plus norethisterone acetate
      reduces homocysteine levels, mainly after a methionine load. This effect seems to
      be independent of vitamin status and may have positive implications for the
      prevention of cardiovascular diseases in PMW.

PMID- 11449083
TI  - The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone
      metabolism.
AB  - OBJECTIVE: This study was undertaken to evaluate the effects of varying doses of
      phytoestrogens on lipid and bone metabolism in postmenopausal women. DESIGN: A
      novel red clover isoflavone preparation (Rimostil) containing genistein,
      daidzein, formononetin, and biochanin was administered to 46 postmenopausal women
      in a double-blind protocol after a single-blind placebo phase and followed by a
      single-blind washout phase. Patients were randomized to receive either 28.5 mg,
      57 mg, or 85.5 mg of phytoestrogens daily for a 6-month period. RESULTS: At 6
      months, the serum high-density lipoprotein cholesterol had risen significantly by
      15.7-28.6% with different doses (p = 0.007, p = 0.002, p = 0.027), although the
      magnitude of the response was independent of the dose used. The serum
      apolipoprotein B fell significantly by 11.5-17.0% with different doses (p =
      0.005, p = 0.043, p = 0.007) and the magnitude of the response was independent of
      the dose used. The bone mineral density of the proximal radius and ulna rose
      significantly by 4.1% over 6 months with 57 mg/day (p = 0.002) and by 3.0% with
      85.5 mg/day (p = 0.023) of isoflavones. The response with 28.5 mg/day of
      isoflavones was not significant. There was no significant increase in endometrial
      thickness with any of the doses of isoflavone used. CONCLUSION: These results
      show that the administration of an isoflavone combination extracted from red
      clover was associated with a significant increase in high-density lipoprotein
      cholesterol, a significant fall in apolipoprotein B, and a significant increase
      in the predominantly cortical bone of the proximal radius and ulna after 6 months
      of treatment. Interpretation of the results is undertaken cautiously because of
      the absence of a simultaneously studied control group.

PMID- 11449084
TI  - Postmenopausal changes in production of type 1 and type 2 cytokines and the
      effects of hormone replacement therapy.
AB  - OBJECTIVE: An appropriate defense against infective agents or malignant cells is
      attributed to the exquisitely balanced T helper 1 type (cellular) and T helper 2
      type (humoral) immune reactions. We investigated the effect of hormone
      replacement therapy (HRT) on postmenopausal changes in the production of
      interferon (IFN)-gamma and interleukin (IL)-10, a type 1 and a type 2 cytokine,
      respectively. DESIGN: Both cytokines were measured by ELISA in the supernatant of
      lipopolysaccharide-stimulated whole blood cells from 72 untreated and 44 HRT
      treated women. Thirteen women were examined before and during HRT. RESULTS: The
      production of IFN-gamma in women in their 40s and in postmenopausal women was
      significantly higher compared with that of younger women. However, IFN-gamma fell
      to the lowest level in the late postmenopausal stage, whereas the production of
      IL-10 increased gradually with age and in parallel with the postmenopausal
      period. Thus, in women in the mid-and late postmenopausal period, excessive
      production of type 2 cytokine (IL-10) compared with type 1 cytokine (IFN-gamma)
      occurred. The IFN-gamma levels of women on HRT were significantly lower than
      those of untreated women in the early and mid-postmenopausal stages, and IL-10
      levels of women on HRT were significantly lower than those of untreated women in
      the mid-and late postmenopausal stages. HRT induced a significant decrease in the
      production of IL-10 and tended to lower the level of IFN-gamma. CONCLUSIONS:
      Production of IL-10 is augmented in postmenopausal women. HRT probably prevents
      postmenopausal women from an aberration of the immune system by improving the
      balance of type 1 and type 2 immune reactions.

PMID- 11449085
TI  - Influence of estrogen replacement therapy on plasma lipid peroxidation.
AB  - OBJECTIVE: To observe whether any relationship exists between the concentration
      of plasma estradiol (E2) and the plasma concentrations of malondialdehyde (MDA)
      or whether a relationship exists between the concentration of plasma E2 and the
      activity of the erythrocyte enzymes, superoxide dismutase (SOD) and catalase, in
      ovariectomized female Wistar rats (treated and untreated with E2). DESIGN: We
      used 40 ovariectomized Wistar rats randomly assigned to four groups. The first
      group was allowed to evolve freely with no treatment. A gel containing 17beta
      estradiol was administered transdermally to the other three groups at doses of 4,
      8, and 16 microg/day, respectively. After 15 days of treatment, blood samples
      were obtained from the four groups. The concentrations of plasma MDA and E2 and
      the activities of erythrocyte catalase and SOD were determined. RESULTS: There
      were significant correlations between the MDA levels and the logarithm (base 10)
      of the plasma E2 concentrations in both linear (p = 0.00093) and quadratic (p =
      0.000001) regression analyses. No relationship was found between the E2
      concentrations and the catalase and SOD activities. CONCLUSIONS: There was a
      clear relationship between the plasma levels of MDA and the logarithm of the
      plasma E2 concentrations, which was best demonstrated with a quadratic
      regression. This model may explain the contradictory findings presented by
      estrogens with respect to their pro-or antioxidant action.

PMID- 11449086
TI  - Previous exposure to hormone replacement therapy and confounders in metabolic
      studies.
AB  - OBJECTIVE: The quantity of intra-abdominal fat is highly associated with the
      development of diabetes mellitus. We sought to determine whether recent hormone
      replacement therapy (HRT) use modifies central fat and insulin sensitivity in
      postmenopausal women compared with women who had never used HRT. DESIGN: We
      measured intra-abdominal fat, subcutaneous abdominal fat, and sagittal diameter
      at the L4-L5 vertebral disc space using computed tomography imaging. Total body
      fat and fat-free mass were measured using dual energy x-ray absorptiometry.
      Insulin sensitivity was assessed using the euglycemic hyperinsulinemic clamp
      technique in 42 nonobese postmenopausal women, age 51 +/- 4 years (12 recent HRT
      users plus 30 never-users). All women who were taking HRT discontinued it for 2
      months before the study. RESULTS: After statistical adjustment for age, previous
      use of HRT was associated with decreased intra-abdominal fat (72 +/- 34 cm2)
      compared with no HRT use (96 +/- 33 cm2; p = 0.05). This difference remained
      significant after adjustment for time since menopause. When previous HRT users
      were compared with nonusers, there were no differences in subcutaneous abdominal
      fat, sagittal diameter, fat-free mass, total fat, insulin sensitivity, or body
      weight. CONCLUSIONS: Recent HRT use is associated with lower intra-abdominal fat
      in nonobese, early postmenopausal women. This finding suggests a carry-over
      effect of HRT on intra-abdominal fat. Recent HRT use does not seem to be
      associated with differences in glucose disposal.

PMID- 11449087
TI  - A scheme of combined oral contraceptives for women more than 40 years old.
AB  - OBJECTIVE: To study whether the addition of estrogen to the 7 hormone-free days
      of a combined oral contraceptive (OC) cycle improves the symptomatology in
      perimenopausal women with climacteric complaints. DESIGN: A total of 56 women in
      their forties presenting with mood disorders and/or hot flashes were included in
      this randomized double-blind study. Symptoms were evaluated using the Greene
      test. Subjects were allocated into two groups: 23 women received an OC containing
      20 microg of ethinyl-estradiol and 150 mg of desogestrel for 21 days and then 7
      placebo tablets (placebo group); the other 33 women received 21 tablets with the
      same hormone combination, followed by 2 placebo tablets and 5 ethinyl-estradiol
      tablets of 10 microg each (estrogen group). After three cycles, symptoms were
      reassessed. RESULTS: Symptoms were similar in the two groups at the start of the
      study. Three months later, vasomotor symptoms in the placebo group dropped from
      3.3 +/- 1.7 to 1.7 +/- 1.8, and in the estrogen group, from 3.0 +/- 1.7 to 0.7 +/
      0.9 (p < 0.04). Similarly, symptoms of depression fell from 8.8 +/- 4.0 to 6.7
      +/- 3.9 in the placebo group and from 10.3 +/- 3.5 to 3.8 +/- 2.9 in the estrogen
      group (p < 0.002). Somatic symptoms fell with placebo from 10.9 +/- 5.3 to 7.4 +/
      5.4, and with estrogen, from 9.7 +/- 4.9 to 4.0 +/- 2.5 (p < 0.03). Sexual
      dysfunction as measured by the Greene Scale (loss of sexual interest) also
      improved more in women who received additional estrogen: 2.0 +/- 0.9 to 0.5 +/-
      0.9 vs. 1.8 +/- 1.2 to 1.2 +/- 1.2, p < 0.03. Anxiety symptoms improved in both
      groups but without any significant difference between them. CONCLUSIONS: Adding 5
      days of estrogen to the classic contraceptive scheme improves the climacteric
      symptoms of perimenopausal women who use OCs.

PMID- 11449088
TI  - General and medical factors associated with hormone replacement therapy among
      women attending menopause clinics in Italy.
AB  - OBJECTIVE: The objective of the study was to analyze medical and general factors
      associated with hormone replacement therapy (HRT) use in women attending a
      network of menopause clinics in Italy. DESIGN: Between 1997 and 1999, we
      conducted a large cross-sectional study on the characteristics of women around
      menopause attending a network of first level outpatient menopause clinics for
      general counseling about menopause or treatment of menopausal symptoms. All women
      consecutively observed during the study period at the participating centers were
      eligible for the study. A total of 42,464 women (mean age 54 years) entered the
      study. The characteristics of women who had at some time used HRT were compared
      with those of women who were never users. RESULTS: Of the 42,464 women
      considered, 4,909 (11.6%) reported having used HRT at some time. In comparison
      with premenopausal women, the odds ratio (OR) of HRT use was 2.1 and 4.0,
      respectively, in women with natural and surgical menopause; the frequency of use
      tends to be lower in women with later age at menopause. In comparison with women
      reporting primary school education, the OR was 1.4 in women with a secondary or
      university degree. In comparison with nulliparity, the OR of HRT use was 0.7 (95%
      confidence interval [CI] 0.6-0.7) in women with two or more births. HRT use was
      less frequent in women reporting a history of diabetes (OR 0.7, in comparison
      with women with no history, 95% CI 0.5-0.9) and cardiovascular diseases (OR 0.8,
      95% CI 0.7-0.8) and more frequent in women with a history of
      osteopenia/osteoporosis (OR 1.2, 95% CI 1.0-1.5), but the latter finding was not
      statistically significant. CONCLUSION: The results of the study indicate that HRT
      use is more common in this population in women of higher education with early age
      at menopause and with a history of osteoporosis/osteopenia and less frequent in
      women with a history of cardiovascular disease and diabetes.

PMID- 11449089
TI  - Estradiol regulates monocyte chemotactic protein-1 in human coronary artery
      smooth muscle cells: a mechanism for its antiatherogenic effect.
AB  - OBJECTIVE: The protective effect of estrogen against early atherosclerosis in
      animal models is well documented, but the mechanisms responsible for this effect
      are not well understood. The earliest recognizable event in the pathogenesis of
      atherosclerosis is an increased recruitment of macrophages into the arterial
      subendothelium. Macrophages first play a protective role by removing low-density
      lipoproteins, but when the cholesterol is in excess, macrophages are converted
      into foam cells and form atheromas. Recent human and animal data indicate that
      the recruitment of macrophages to the arterial wall is mediated by monocyte
      chemotactic protein-1 (MCP-1). We hypothesized that one of the mechanisms of
      estrogen's protective effect against atherosclerosis may be the down-regulation
      of MCP-1 expression in the arterial wall. DESIGN: Human coronary artery smooth
      muscle cells were replicated to confluence in smooth muscle cell basal medium
      supplemented with growth factors and 5% fetal bovine serum. Before each
      experiment, cells were incubated for 24 h with phenol red-free medium containing
      5% charcoal-stripped calf serum, and then they were treated with various
      concentrations of 17beta-estradiol as well as selective estrogen receptor (ER)
      modulators, raloxifene and tamoxifen. MCP-1 messenger ribonucleic acid (mRNA)
      levels were quantified by Northern blots. MCP-1 protein was quantified using an
      enzyme-linked immunosorbent assay. ER expression was evaluated by reverse
      transcriptase-polymerase chain reaction. RESULTS: Human coronary artery smooth
      muscle cells expressed MCP-1 mRNA and produced MCP-1 protein. Estradiol induced
      up to 40% inhibition in mRNA expression at concentrations 10-9 M and higher.
      Raloxifene and tamoxifen also resulted in an inhibition, but the inhibition was
      less than when induced by estradiol. Estradiol also inhibited the MCP-1 protein
      production in a concentration-dependent manner (p < 0.05). Coronary smooth muscle
      cells expressed both ERalpha and ERbeta. CONCLUSION: Our findings suggest that
      one of the mechanisms by which estrogen prevents atherosclerosis is by down
      regulating MCP-1 expression, thus decreasing macrophage recruitment to the
      arterial wall.

PMID- 11449090
TI  - New evidence that nicotine affects eye movement and balance in susceptible
      individuals.

PMID- 11449091
TI  - Human neural stem cells improve cognitive function of aged brain.

PMID- 11449093
TI  - The first nail in the coffin.

PMID- 11449092
TI  - How does the brain determine whether enhanced cognition or anxiety is the
      appropriate response to a stress?

PMID- 11449094
TI  - Cartilage palisade tympanoplasty and diving.
AB  - OBJECTIVE: To determine whether a patient with a serious defect of the tympanic
      membrane (TM) will be able to dive after surgery. PATIENTS AND METHODS: The
      authors describe three patients who were divers with serious defects of the TM
      (more than 75% of TM). In all three cases, cartilage palisade tympanoplasty was
      used to reconstruct the TM. RESULTS: Six months after surgery, the patients
      passed clinical examinations, audiograms (hearing restored to normal),
      tympanometry (increased stiffness of the TM), and pressure tolerance tests in
      hyperbaric chamber (30-m immersion was simulated for 4 minutes), and they began
      to dive again. Approximately 2 years after the surgery, all three patients are
      able to dive without any difficulties. CONCLUSION: The authors conclude that
      patients can dive after cartilage palisade tympanoplasty.

PMID- 11449095
TI  - Foreign body neonatal otitis media in infants.
AB  - HYPOTHESIS: An influx of amniotic fluid cellular content (AFCC) into the middle
      ears during birth may lead to the development of a chronic inflammatory process
      in the form of varying amounts of granulation tissue even if signs of otitis
      media are absent. This foreign body neonatal otitis media may predispose the
      child to recurrent otitis media. BACKGROUND: Foreign body neonatal otitis media
      caused by AFCC was described by Aschoff and elaborated by Wittmaack 100 years
      ago. Recent studies have shown how AFCC spreads to various middle ear
      compartments and causes histologic changes, the severity of which is related to
      the amount of AFCC. Specific elements become phagocytized after the first months
      of life but have caused the formation of inflammatory polyps and granulation
      tissue with round cell secretions in the meantime. METHODS: Ten temporal bones
      from the Temporal Bone Foundation, derived from infants aged 5 months to 1 year
      11 months, were serially sectioned at 20 microm, saved at 0.2-mm intervals,
      numbered, and stained with hematoxylin and eosin. Every slide was studied for the
      presence, nature, and stage of pathologic tissue changes of the middle ear and
      the mastoid antrum. RESULTS: Pseudocystic granulation tissue was massive in the
      temporal bone of the 8-month-old child born through thick meconium. Severe
      changes were present in the temporal bones of two infants aged 5 months, one of
      which showed traces of AFCC. In the temporal bones of two older children, long
      standing changes were minor, one of them still showed traces of AFCC. Fresh acute
      changes and long-standing histologic changes occurred side by side. CONCLUSIONS:
      Neonatal otitis media caused by AFCC can give rise to extensive granulation
      tissue and round cell secretion, which is likely to make the ear susceptible to
      infectious otitis media. Cumulative development of granulation tissue as a result
      of infection may lead to blockage of attic aeration and drainage pathways,
      causing irreversible adhesive otitis media. A data base should be formed of all
      neonates born through meconium-stained amniotic fluid to allow a comparison with
      those born through clear fluids. Surgery with the creation of auxiliary aeration
      pathways becomes advisable in the treatment of ears with massive development of
      granulation tissue.

PMID- 11449096
TI  - Cholesteatoma behind an intact tympanic membrane: histopathologic evidence for a
      tympanic membrane origin.
AB  - BACKGROUND: Several theories have been proposed with respect to the origin and
      pathogenesis of cholesteatoma behind an intact tympanic membrane. CASE REPORT:
      The authors describe a case of cholesteatoma behind an intact tympanic membrane
      in a 71-year-old man with a history of tympanic membrane retraction fixed to the
      incus without evidence of a perforation. The membrane eventually became detached,
      and remnants of keratinizing squamous epithelium were found on the incus.
      DISCUSSION: Mechanisms such as metaplasia, ectopic epidermis rests, or ingrowth
      of meatal epidermis have been proposed to explain the pathogenesis of
      cholesteatoma behind an intact tympanic membrane. These findings, based on
      temporal bone histopathology, support the role of an acquired epidermal rest.
      CONCLUSIONS: This case report provides evidence that cholesteatoma behind an
      intact tympanic membrane can be established from a resolved retraction of the
      pars tensa of the tympanic membrane.

PMID- 11449097
TI  - Chronic middle ear disease and gastroesophageal reflux disease: a causal
      relation?
AB  - OBJECTIVE: To describe one patient with a puzzling therapy-resistant unilateral
      chronic otitis media, analyze his diagnosis, and describe three similar patients
      with the same symptoms and signs, i.e., a chronic ear problem together with
      gastroesophageal reflux disease (GERD). STUDY DESIGN: Thorough analysis of one
      patient with a chronic ear problem and GERD, both of which responded favorably
      after antireflux therapy consisting of omeprazole and conservative antireflux
      measures (raising the head of the bed by 20 to 25 cm, avoiding meals and drinks 3
      hours before retiring, and other dietary and lifestyle modifications), and a
      search for more patients with similar coexisting conditions. SETTING: Tertiary
      referral center. METHODS: Patients with chronic ear problems and GERD were
      thoroughly analyzed by the otorhinolaryngologist and the gastroenterologist. The
      latter used endoscopy and Savary-Miller's classification of esophagitis, a 24
      hour ambulatory dual esophageal pH monitoring, and esophageal manometry. RESULTS:
      Four patients were identified who had a chronic ear problem and simultaneous
      GERD. It is reasoned that the GERD leads to nasopharyngitis and this to a chronic
      ear problem. All the patients responded favorably to anti-GERD therapy.
      CONCLUSIONS: GERD may manifest itself as an extraesophageal manifestation, such
      as nasopharyngitis, leading to ear disease. Therapy-resistant chronic middle ear
      disease may be caused by GERD.

PMID- 11449098
TI  - Canal-down mastoidectomy: experience in 81 cases.
AB  - OBJECTIVES: To identify the common presentation(s) and the clinical and operative
      finding(s) in patients with cholesteatomatous and long-term noncholesteatomatous
      chronic suppurative otitis media and to adapt a surgical management best suited
      to ensure long-term safety in these Papua New Guinean patients for whom
      postoperative follow-up is minimal. DESIGN: Retrospective case series. SETTING:
      Port Moresby General Hospital, the tertiary referral center for otolaryngologic
      services. PATIENTS: Eighty-one patients in all age groups who received a clinical
      diagnosis of chronic suppurative otitis media, with or without cholesteatoma,
      with or without its associated complications. INTERVENTION: Canal-down (modified
      radical) mastoidectomy with wide meatoplasty. MAIN OUTCOME MEASURE AND RESULTS:
      Adults were more commonly affected than adolescent or pediatric cases, and there
      was a male preponderance. The median age was 24 years (range, 13 months to 73
      years). Otorrhea remained the most common presentation in all age groups.
      Postauricular abscesses and fistulae were seen frequently. Cholesteatoma and
      granulation with polypoidal mucosa were frequent operative findings; a high
      incidence involved both the attic space and the antrum. Five (6%) patients had
      preoperative facial paralysis; in addition, postoperative facial paralysis
      developed in three (4%) patients. The incidence of postoperative "wet ear" was
      high in all age groups. Meningitis was the most common intracranial complication,
      followed by lateral sinus thrombosis. There were seven (9%) deaths altogether,
      and all the deaths occurred as a direct result of otogenic intracranial
      complication. CONCLUSION: Lack of health consciousness, poor socioeconomic
      status, and lack of health care delivery system resulted in late presentations
      and poor postoperative follow-up. Hence, the canal-wall-down technique with wide
      meatoplasty is recommended to ensure a best possible one-time treatment in Papua
      New Guinean patients with cholesteatomatous or long-term "dangerous" chronic
      suppurative otitis media with or without complications.

PMID- 11449099
TI  - M-meatoplasty: results and patient satisfaction in 125 patients (199 ears).
AB  - OBJECTIVE: Is M-meatoplasty the solution for chronic otitis externa caused by wax
      retention? This study discusses acceptance of this operation and whether sedation
      is necessary. STUDY DESIGN: Between October 1994 and October 1997, 199 successive
      M-meatoplasties (125 patients) were studied, and 79% of the patients completed a
      questionnaire in which patient satisfaction with the procedure and outcome was
      assessed. SETTING: Local hospital, functioning as a secondary referral center.
      PATIENTS: All patients had narrowing of the lateral part of the outer ear canal
      resulting from anterior displacement of the cavum conchae cartilage.
      INTERVENTION: The aim of M-meatoplasty is to increase the lumen of the entrance
      to the external ear canal by reducing the conchal cartilage on the posterior wall
      MAIN OUTCOME MEASURES: Reduction of visits to the outpatient clinic, patient
      satisfaction on a scale from 1 (very bad) to 10 (excellent). RESULTS: The number
      of preoperative visits was 7 (range 1-153). The median number of postoperative
      visits for the same problems more than 3 months after surgery was 1 (range 0-14).
      The patient score for the surgery and the final result was a median of 9 (very
      good). CONCLUSIONS: Wax obstruction and related external otitis can be cured by M
      meatoplasty if the conchal cartilage is too prominent on the posterior wall. It
      is a simple outpatient operation and is very well tolerated. After the operation,
      there is an enormous reduction in outpatient visits.

PMID- 11449100
TI  - Correlations between computed tomography findings and family history in
      otosclerotic patients.
AB  - BACKGROUND: Otosclerosis is a heritable disease affecting the otic capsule. Its
      genetics have been studied since the 19th century, but several issues remain
      controversial. OBJECTIVE: The goals of this study were to assess the prevalence
      of sporadic and familial forms of otosclerosis in a population of otosclerotic
      patients and to compare the radiologic findings between both groups. STUDY DESIGN
      AND SETTING: This retrospective study was conducted in a single institution.
      PATIENTS: This study included 211 patients operated on for otosclerosis. MAIN
      OUTCOME MEASURES: Clinical data, including pure tone audiograms, were available
      from patients' charts. A questionnaire assessing family history of otosclerosis
      and deafness was mailed to the otosclerotic patients. A relative was considered
      otosclerotic if surgery confirmed the disease. The family history was correlated
      with the computed tomography results. This examination was performed before
      surgery in all patients. RESULTS: A family history of otosclerosis was found in
      24.2% of the patients. The radiologic findings differed between patients with a
      sporadic form of otosclerosis and those with a familial form. The lesions were
      more often detectable, bilateral, and severe in the familial forms (p < 0.05).
      CONCLUSION: These findings lead to the assumption that fenestral radiologic
      otosclerosis occurs more in sporadic forms, whereas more extensive lesions on
      computed tomography seem to indicate the familial forms. Hereditary forms
      demonstrated to be familial seem to lead to more severe disease. The search for a
      genome locus of otosclerosis may be enlightened by these findings.

PMID- 11449101
TI  - Delayed facial palsy after stapedectomy.
AB  - OBJECTIVE: To study the incidence, pathogenesis, and prevention of delayed facial
      palsy after stapedectomy. STUDY DESIGN: Retrospective case review. SETTING:
      Otology/neurotology referral center. PATIENTS: A series of 2152 stapedectomy
      procedures in 2106 patients over 12 years. INTERVENTION: Delayed facial palsy
      after stapedectomy was studied. MAIN OUTCOME MEASURE: House-Brackmann facial
      nerve grading system and serum antibody titer tests for herpes simplex virus type
      I and type II, and varicella zoster virus. RESULTS: Delayed facial palsy occurred
      in 11 of 2152 procedures. Delayed facial palsy occurred from 5 to 16 days (mean
      8) after stapedectomy. Predisposing factors were bony facial canal dehiscence
      with bare or bulging facial nerve herniation in 5 patients; chorda tympani nerve
      stretched, manipulated, or cut in 2 patients; granulomatous reaction to Gelfoam
      in 1 patient; fever blisters on the upper lip in 1 patient; and sinusitis in 2
      patients. Elevated anti-varicella antibody titers were found in all 6 patients
      studied. Anti-herpes simplex type I and II antibody titers were elevated in 5 of
      6 patients. Acyclovir was effective in preventing delayed facial palsy in 1
      patient who had undergone revision stapedectomy and experienced delayed facial
      palsy after previous stapedectomy in the same ear with elevated anti-herpes
      antibody titer. CONCLUSIONS: Delayed facial palsy occurred in 0.51% of patients
      after stapedectomy. Serologic investigation suggests activation of latent
      herpesvirus. Mechanical irritation of the facial or chorda nerve during operation
      may trigger the activation. The anti-herpesvirus agent acyclovir may prevent
      delayed facial palsy after stapedectomy in patients suspected of having this
      complication.

PMID- 11449102
TI  - Management of far advanced otosclerosis in the era of cochlear implantation.
AB  - OBJECTIVE: To evaluate issues pertaining to cochlear implantation in patients
      with far advanced cochlear otosclerosis. STUDY DESIGN: Prospective cohort.
      SETTING: Tertiary care referral center. PATIENTS: Eight adult patients (18 years
      of age or older) referred for management of profound hearing loss, the cause of
      which was determined to be otosclerosis. INTERVENTION: Cochlear implantation with
      multichannel cochlear implant device. MAIN OUTCOME MEASURES: Benefit from
      cochlear implant as measured by CID sentence scores, incidence and management of
      facial nerve stimulation, and technical issues pertaining to cochlear
      implantation in this patient population. RESULTS: All patients demonstrated
      significant improvement in auditory function as measured by performance on CID
      sentence scores and ability to engage in telephone conversation. Facial nerve
      stimulation was present in two of eight patients and was managed with
      deactivation of the stimulating electrodes. Ossification in the basal turn of the
      cochlea, detected on preoperative computed tomography, necessitated placement of
      the electrode into the scala vestibuli in two patients and use of a thinner
      electrode (Nucleus 24) in a third patient. CONCLUSION: Patients with profound
      hearing loss secondary to otosclerosis derive excellent benefits from cochlear
      implantation. Surgical implantation may be complicated by ossification of the
      cochlea, which can be detected on preoperative computed tomography. Electrode
      activation may be complicated by facial nerve stimulation, which can be addressed
      with programming strategies.

PMID- 11449103
TI  - Targeted topical steroid therapy in sudden sensorineural hearing loss.
AB  - OBJECTIVE: To treat patients with sudden sensorineural hearing loss (SSNL) who
      failed oral prednisone therapy by using a round window membrane (RWM)
      microcatheter. This topical delivery strategy sought to improve effectiveness of
      steroid treatment to the inner ear by targeting drug delivery to the RWM. STUDY
      DESIGN: Nonrandomized prospective design. SETTING: Tertiary care facility.
      PATIENTS: Six patients with severe unilateral SSHL, five of whom were refractory
      to a course of oral steroid therapy treated within 6 weeks of SSHL and three
      additional patients treated more than 6 weeks after SSHL. INTERVENTION:
      Therapeutic use of RWM catheter. MAIN OUTCOME MEASURES: Pure-tone averages (PTAs)
      and word identification scores (WIS). RESULTS: Five of the six patients treated
      within 6 weeks of SSHL improved their WIS. Of the six, four returned to baseline
      hearing, one recovered hearing that could benefit by hearing amplification, and
      one regained moderate improvement in PTA but not WIS. CONCLUSION: Targeted
      topical steroid administration avoids the significant systemic side effects of
      oral steroids and may offer more effective dosing than simple transtympanic
      injection of medicine. Although these findings are preliminary, it is possible
      that after further study, targeted drug delivery may be a useful technique to
      consider in patients with severe to profound hearing loss that have failed all
      other management options.

PMID- 11449104
TI  - The minimum speech test battery in profound unilateral hearing loss.
AB  - OBJECTIVE: Individuals with monaural hearing experience disadvantages compared
      with normal hearing counterparts because of the loss of the head shadow effect,
      the squelch effect, and binaural summation. In this study the Minimum Speech Test
      Battery (MSTB), a battery designed to document word recognition in bilaterally
      hearing impaired cochlear implant candidates, was administered to unilaterally
      hearing-impaired and normal hearing subjects to study its possible use in
      measuring hearing difficulty in monaural subjects. STUDY DESIGN: Repeated
      measures design with the MSTB administered in sound-field in a sound-isolated
      booth in 1) quiet; 2) speech toward good ear, noise (+10 dB S/N) toward impaired
      ear; 3) speech toward impaired ear, noise toward good ear; and 4) bilateral
      speech and noise. SETTING: Academic otologic practice. PATIENTS: Ten adults with
      normal hearing and 10 adults with normal or near-normal hearing in one ear and
      profound hearing loss in the contralateral ear. MAIN OUTCOME MEASURES: The MSTB,
      composed of the Consonant-Nucleus-Consonant (CNC) test and the Hearing In Noise
      Test (HINT). RESULTS: As expected, performance differences between the groups
      were not found in quiet conditions. Analysis of variance and regression analysis
      confirmed that the impaired group performed significantly worse than control
      subjects on HINT testing when noise was directed toward the good ear. Analysis of
      variance and regression analysis confirmed that the impaired group performed
      significantly worse than control subjects on CNC testing when noise was directed
      toward the good ear and in bilateral noise. CONCLUSIONS: The MSTB may be useful
      in measuring the hearing difficulty of patients with monaural hearing.

PMID- 11449105
TI  - Vibratory sample magnetometry of middle ear prostheses and manufacturing
      materials.
AB  - OBJECTIVE: To assess the magnetic properties of stapes prostheses and
      manufacturing materials using a vibratory sample magnetometer (VSM). DATA
      SOURCES: VSM was performed on 16 samples, including ferromagnetic 420F stainless
      steel, with an LDJ Model 9600 VSM in accordance with American Society for Testing
      and Materials standard A894. RESULTS: A VSM measures the magnetic dipole moment
      of a sample in a magnetic field. The magnetic field is swept over a range of
      magnetic fields, and the magnetic dipole moment is plotted as a function of
      field. The prostheses made of 316L stainless steel previously found to be
      ferromagnetic had the highest specific magnetic moments. The specific magnetic
      moments ranged from 0.023 electromagnetic units (emu)/g to 156 emu/g. The samples
      made with 316L stainless steel, which is used in otologic implants, were
      significantly less magnetic than was the 420F stainless steel. CONCLUSION: VSM
      demonstrates that prostheses made with 316L stainless steel are relatively
      nonferromagnetic compared with 420F stainless steel. However, none of the
      implants are nonmagnetic. The torque and linear force on the prosthesis is a
      concern. The safety of performing MRI on patients with these implants needs to be
      further assessed.

PMID- 11449106
TI  - Eighth nerve aplasia and hypoplasia in cochlear implant candidates: the clinical
      perspective.
AB  - OBJECTIVE: To identify the clinical and radiologic characteristics of aplasia and
      hypoplasia of the eighth nerve. STUDY DESIGN: Retrospective case-note review.
      SETTING: Cochlear implant program. PATIENTS: All children at the authors'
      institution in whom the cochlear implant assessment failed because of absence or
      hypoplasia of the eighth nerve. INTERVENTION: Computed tomography of petrous
      bones and magnetic resonance imaging of the brain. MAIN OUTCOME MEASURES:
      Presence or absence of eighth nerve and other radiologic factors contraindicating
      implantation. RESULTS: Of 143 cochlear implant candidates, 237 were judged
      ineligible for cochlear implantation. The preimplant assessment failed in 10
      candidates of 143 because of bilateral aplasia or hypoplasia of the eighth nerve
      (7 cases) or unilateral aplasia or hypoplasia of the eighth nerve and a
      contraindication to operation on the other side (3 cases). The aplasia or
      hypoplasia of the eighth nerve was confirmed by magnetic resonance imaging in
      seven cases (5%): six were syndromic (3 CHARGE, 1 VATER-RAPADILLINO, 1 Mobius, 1
      Okihiro), and one was nonsyndromic autosomal-recessive. All seven children had
      delayed motor milestones and absence of auditory brainstem responses. CONCLUSION:
      Aplasia and hypoplasia of the eighth nerve are not uncommon in pediatric cochlear
      implant candidates, particularly in the presence of a syndrome such as CHARGE.
      Magnetic resonance imaging of the brain is mandatory before implantation because
      it can identify the presence or absence of the eighth nerve. Parents of children
      with profound hearing loss, delayed motor milestones, absence of auditory
      brainstem responses, and a syndromic diagnosis, should be made aware of this
      possible abnormality.

PMID- 11449107
TI  - Is cochlear implantation possible after acoustic tumor removal?
AB  - HYPOTHESIS: This study aimed to assess the possibility of hearing restoration
      after acoustic tumor removal. BACKGROUND: Hearing restoration surgery may be
      indicated after surgery of bilateral acoustic tumors or surgery of acoustic tumor
      in the only hearing ear. The choice is between cochlear implantation and
      brainstem implantation. METHODS: From the temporal bone collection at the House
      Ear Institute, Los Angeles, the author histologically examined eight temporal
      bones from seven patients who had undergone acoustic tumor removal during their
      lifetime. Special emphasis was put on examining the patency of the cochlear turns
      and on survival of the spiral ganglion cells and cochlear nerve. RESULTS: This
      study showed that after translabyrinthine acoustic tumor removal, there is
      progressive osteoneogenesis of the cochlea associated with almost complete
      degeneration of the spiral ganglion cells and cochlear nerve. Similar findings
      were noticed after middle fossa removal of acoustic tumor with unsuccessful
      hearing preservation. CONCLUSIONS: The histologic changes described in the
      cochlea and cochlear nerve represent the effects of ischemia resulting from
      inadvertent cutting of the blood supply during acoustic tumor removal. It is
      possible to do cochlear implantation after acoustic tumor removal provided that
      the result of promontory electrical stimulation test is positive (the cochlear
      nerve is intact) and that implantation is done at the time of acoustic tumor
      removal or shortly thereafter, before cochlear ossification is complete.

PMID- 11449108
TI  - Goldenhar's syndrome: congenital hearing deficit of conductive or sensorineural
      origin? Temporal bone histopathologic study.
AB  - BACKGROUND: Oculoauriculovertebral dysplasia (OAVD) (Goldenhar's syndrome) is a
      congenital syndrome with ipsilateral deformity of the ear and face, epibulbar
      lipodermoids, coloboma, and vertebral anomalies. Goldenhar's anomaly has often
      been associated with a degree of congenital hearing deficits, almost always of a
      conductive origin, but a sensorineural component is also suspected in some cases,
      evident through malformations of the inner ear. PATIENTS AND METHODS: Both
      temporal bones of a 10-day-old deceased patient with oculoauriculovertebral
      dysplasia were examined by light microscopy. RESULTS: The ear deformities
      included deformity of the auricle, atresia of the external auditory canal, and
      malformation of the tympanic cavity and ossicles. Abnormalities of the stria
      vascularis and the semicircular canals were also demonstrated. Further inner ear
      deformities were not identified in this case. CONCLUSION: These histopathologic
      findings appear to confirm the conductive component of the congenital hearing
      deficit, but a sensorineural component could not be omitted. The ear alterations
      favor early developmental field defects. The causes of this condition are
      controversial. Recent results in genetic research pertaining to the MSX class
      genes permit better understanding of the variety, variability, and different
      degrees of severity of the anomalies described here.

PMID- 11449109
TI  - Temporal bone histopathologic and genetic studies in Mohr-Tranebjaerg syndrome
      (DFN-1).
AB  - OBJECTIVE: To describe the temporal bone histopathologic and genetic
      abnormalities in a case of Mohr-Tranebjaerg syndrome. BACKGROUND: Mohr
      Tranebjaezrg syndrome (DFN-1) is an X-linked, recessive, syndromic hearing loss,
      characterized by postlingual sensorineural hearing loss with onset in childhood,
      followed in adult life by progressive dystonia, spasticity, dysphagia, and optic
      atrophy. The syndrome is caused by mutations in the DDP (deafness/dystonia
      peptide) gene, which are thought to result in mitochondrial dysfunction with
      subsequent neurodegeneration. The temporal bone pathologic changes in this
      syndrome have not been reported. METHODS: Hearing loss developed in the patient
      at age 4, blindness at age 48, and dystonia at age 57. Genetic studies on
      peripheral blood showed a l51delT mutation in his DDP gene. He died at age 66.
      The right temporal bone was subjected to light microscopy and polymerase chain
      reaction-based analysis of the DDP gene sequence. RESULTS: There was near
      complete loss of spiral ganglion cells with loss of nearly all peripheral and
      central processes. Only 1,765 spiral ganglion cells remained (8.5% of mean normal
      for age). The organ of Corti (including hair cells), stria vascularis, and spiral
      ligament were preserved. There was also a severe loss of Scarpa's ganglion cells
      with preservation of vestibular hair cells. The population of geniculate and
      trigeminal ganglion cells appeared normal. Sequence analysis from temporal bone
      DNA showed the 15ldelT DDP gene mutation. CONCLUSION: Sensorineural hearing loss
      in Mohr-Tranebjaerg syndrome is the result of a postnatal, progressive, severe
      auditory neuropathy.

PMID- 11449110
TI  - Anatomic considerations in vestibular neuritis.
AB  - HYPOTHESIS: The authors believe that anatomic differences render the superior
      division of the vestibular nerve more susceptible to injury during vestibular
      neuritis. The purpose of the study was to investigate anatomic differences
      between the superior vestibular nerve and singular nerve canals. BACKGROUND:
      Previous studies of temporal bones have revealed vestibular nerve degeneration in
      patients with vestibular neuritis. Although the cause of this degeneration has
      not been established, it has been noted that the superior division of the
      vestibular nerve is preferentially affected, with sparing of the inferior
      division. The superior vestibular nerve and the singular nerve, a branch of the
      inferior vestibular nerve, both pass through canals interlaced with bony networks
      before reaching the peripheral receptors. METHODS: The authors performed
      histologic analysis of 40 normal temporal bones randomly selected from their
      temporal bone library. With a micrometer, measurements were taken of the
      individual canals. The ratio of the total bony spicule component to the total
      canal width was obtained for both the superior vestibular nerve and the singular
      nerve. The length of the canals was also measured. Arteriole:arteriolar canal
      ratios of the superior vestibular nerve and singular nerve were obtained.
      RESULTS: The bony channel of the singular nerve had an average length of 0.59 mm,
      and the average length of the superior vestibular nerve was 2.30 mm (p < 0.001).
      The ratio of total bony spicule width to total canal width was significantly
      smaller (p < 0.05) for the singular nerve (0.30 mm) compared with the superior
      vestibular nerve (0.34 mm). The arteriole: arteriolar canal ratio was
      significantly smaller (p < 0.05) for the singular nerve (0.45 mm) than for the
      superior vestibular nerve (0.54 mm). CONCLUSION: The bony canal of the superior
      vestibular nerve is longer than the singular nerve canal. Additionally, the
      superior vestibular nerve and arteriole travel through a relatively narrower
      passage than the singular nerve and its vascular supply. From an anatomic
      standpoint, this renders the superior division of the vestibular nerve more
      susceptible to entrapment and possible ischemic labyrinthine changes.

PMID- 11449111
TI  - An anatomic variant of the anterior inferior cerebellar artery in a patient with
      Meniere's disease.
AB  - OBJECTIVE: To describe an anatomic variant of the anterior inferior cerebellar
      artery in a patient with Meniere's disease. STUDY DESIGN: Retrospective case
      review and review of the literature. SETTING: Tertiary referral clinic.
      INTERVENTION: Vestibular nerve section and microvascular decompression. MAIN
      OUTCOME MEASURES: Audiometric testing and control of vertigo. RESULTS: The eighth
      nerve was identified via a retromastoid approach. The anterior inferior
      cerebellar artery was observed bisecting the eighth nerve. The vestibular nerve
      was sectioned, and microvascular decompression was performed on the cochlear
      division. At last follow-up, the patient had not experienced any vertiginous
      attacks but was observed to have progressive hearing loss. CONCLUSIONS: The
      course of the anterior inferior cerebellar artery is highly variable and
      difficult to predict. Knowing the potential paths is a necessity in performing
      posterior fossa surgery. Although the patient's vertigo was controlled by the
      vestibular nerve section, microvascular decompression of the cochlear nerve did
      not result in hearing improvement or stabilization. This case report does not
      support a benefit of microvascular decompression in Meniere's disease. Vestibular
      nerve section remains the authors' treatment of choice for controlling disabling
      vertigo caused by Meniere's disease.

PMID- 11449112
TI  - Patients' subjective evaluations of quality of life related to disease-specific
      symptoms, sense of coherence, and treatment in Meniere's disease.
AB  - OBJECTIVE: To evaluate the self-rated quality of life associated with vertigo,
      hearing loss, and tinnitus in Meniere's patients, and to identify potential
      relationships between these findings, treatment regimens, and sense of coherence
      in comparison to the classification of the American Academy of Otolaryngology
      Head and Neck Surgery (AAO/HNS). STUDY DESIGN: Cross-sectional. SETTING: Tertiary
      referral hospital centers. PATIENTS: 112 patients with Meniere's disease, who had
      undergone endolymphatic sac surgery or intratympanic gentamicin injections, or
      were surgically untreated. MAIN OUTCOME MEASURE: Questionnaires concerning
      quality of life aspects and symptom-specific instruments: the Vertigo Symptom
      Scale (VSS), the Hearing Disability Handicap scale (HDHS), the Tinnitus Severity
      Questionnaire (TSQ), the AAO/HNS criteria for reporting results of treatment of
      Meniere's disease, and the Sense of Coherence Scale. RESULTS: A majority of the
      patients reported their quality of life in general as very good or good. There
      was no difference in general quality of life, present hearing loss, or tinnitus
      between the three treatment groups, but the gentamicin-treated patients had less
      vertigo than did the other groups. Sense of coherence showed a strong correlation
      to reported quality of life in all measurements. CONCLUSIONS: Even though the
      gentamicin-treated patients had less vertigo, no difference in overall quality of
      life was found between the surgically treated and untreated patients. The sense
      of coherence seems to be an important factor in the patient's experience of
      quality of life. Quality of life instruments can measure both specific symptoms
      and related aspects on quality of life and may give complementary information to
      the AAO/HNS classification in evaluating the treatment of patients with Meniere's
      disease.

PMID- 11449113
TI  - Relationship of the cochlear aqueduct and inner ear pressure in Meniere's disease
      and in a normal population.
AB  - OBJECTIVE: The aim of this study was to determine the dimensions of cochlear
      aqueduct radiologically in patients with Meniere's disease and in normal
      subjects, and to correlate these findings with normal and low static acoustic
      compliance (SAC) (high and normal perilymphatic pressure) to see whether the
      dimensions of the cochlear aqueduct play any role in the perilymphatic pressure
      in normal individuals and patients with Meniere's disease. STUDY DESIGN:
      Prospective double-blind study. SETTING: The study was conducted at Hacettepe
      University Medical Faculty, a tertiary care center. PATIENTS: Forty patients with
      Meniere's disease with bilateral involvement, diagnosed by vertigo attacks,
      fluctuating hearing loss, tinnitus, fullness in the ear, and cochlear sensitivity
      constituted the patient group. Forty healthy individuals with no otolaryngologic
      symptoms constituted the control group. INTERVENTIONS: All individuals underwent
      SAC measurement in terms of equivalent volume in milliliters, based on two volume
      measurements. To measure the dimensions of the cochlear aqueduct, high-resolution
      computed tomography of the temporal bone in the axial plane was performed.
      RESULTS: There was no statistically significant difference in the width of the
      cochlear aqueduct between patients with Meniere's disease and normal subjects.
      When SAC measurements were also taken into account, there was no difference in
      cochlear aqueduct dimensions between individuals with normal and low SAC values
      in the two groups. CONCLUSION: The dimensions of cochlear aqueduct are not
      significantly different in Meniere's disease patients and normal individuals.
      Also, the cochlear aqueduct does not appear to play a significant role in normal
      and low SAC values in the two groups of individuals.

PMID- 11449114
TI  - Labyrinthectomy versus vestibular neurectomy: long-term physiologic and clinical
      outcomes.
AB  - OBJECTIVE: To determine whether long-term vestibular compensation (VC) and
      clinical outcomes differ after transmastoid labyrinthectomy (TML) versus
      retrolabyrinthine vestibular neurectomy (RVNS). STUDY DESIGN: Prospective,
      observational study. SETTING: Tertiary care, university hospital. PATIENTS:
      Twenty-one subjects were studied several years after they were relieved of
      spontaneous episodic vertigo caused by peripheral vestibular disease by TML or
      RVNS. INTERVENTIONS: All patients had undergone TML or RVNS more than 2.5 years
      before the study and returned for physiologic and functional studies of
      vestibular compensation. MAIN OUTCOME MEASURES: Completeness of physiologic VC,
      as assessed by electronystagmography and rotational chair testing; performance on
      computerized dynamic posturography; pure-tone and speech audiometry; self
      assessment of balance and hearing function with validated survey instruments.
      RESULTS: There were no differences in the incidence of physiologic VC or
      functional recovery between the TML and RVNS subjects. Although a majority of
      subjects in each group had evidence of incomplete vestibular compensation, there
      was no difference in self-assessment of balance or hearing handicap at long-term
      follow-up. CONCLUSIONS: Long-term clinical balance and hearing outcomes are
      equivalent when TML and RVNS successfully cure spontaneous, episodic vertigo.
      There is a high incidence of incomplete VC after both procedures, though this
      does not usually produce a significant balance handicap.

PMID- 11449115
TI  - Herpes virus reactivation and gadolinium-enhanced magnetic resonance imaging in
      patients with facial palsy.
AB  - OBJECTIVE: This study investigated whether magnetic resonance imaging (MRI)
      patterns were different between patients with Bell's palsy and those with
      herpetic facial palsy in whom varicella-zoster virus (VZV) or herpes simplex
      virus type 1 (HSV-1) reactivation had been confirmed by polymerase chain reaction
      (PCR) or serologic assay. STUDY DESIGN: A retrospective study of 15 patients with
      acute peripheral facial palsy was performed to compare virologic tests and
      gadolinium (Gd)-enhanced MRI findings. RESULTS: Ramsay Hunt syndrome was
      diagnosed in one patient. By use of virologic tests, zoster sine herpete (VZV
      reactivation without zoster) was diagnosed in four patients and HSV-1
      reactivation in three. Bell's palsy was diagnosed in the remaining seven
      patients. No significant difference in the frequency of Gd-enhanced MRI was
      observed between herpetic facial palsy and Bell's palsy. However, in those
      patients who underwent MRI on the day viral reactivation was confirmed by PCR, Gd
      enhancement of the meatal fundus was observed infrequently. In addition, when MRI
      was performed within 10 days of the onset of palsy, Gd enhancement was not
      detected at the geniculate ganglion in any patients with herpetic facial palsy.
      By contrast, both the meatal fundus and the geniculate ganglion were enhanced in
      all patients with Bell's palsy, regardless of when MRI was performed with respect
      to the onset of palsy. CONCLUSION: This study shows a difference in the pattern
      of Gd enhancement at the meatal fundus and the geniculate ganglion between
      patients with Bell's palsy and those with herpetic facial palsy. The results
      suggest that the meatal fundus or the geniculate ganglion may be affected first
      by virus reactivation in patients with herpetic facial palsy.

PMID- 11449116
TI  - Electromyographic evaluation of facial nerve damage in acoustic neuroma surgery.
AB  - OBJECTIVE: This study aimed to determine whether postoperative facial nerve
      paralysis or surgical manipulation causing paralysis could be predicted on train
      responses during intraoperative facial nerve monitoring in acoustic neuroma
      surgery. STUDY DESIGN AND SETTING: This was a prospective study performed at a
      tertiary referral center. PATIENTS AND METHODS: Train responses were recorded on
      a floppy disk and compared with postoperative facial nerve function in 51
      patients who underwent enlarged translabyrinthine acoustic neuroma surgery. MAIN
      OUTCOME MEASURES: The number, duration, frequency, and peak-to-peak amplitude of
      train responses were analyzed and compared with postoperative facial nerve
      function. RESULTS: Trains were observed in 42 of 51 patients. Six of seven
      patients with high-amplitude trains more than 250 microV, and three of five
      patients with bomber-type high-frequency trains elicited during tumor dissection
      from the facial nerve or stretching the nerve, showed severe facial nerve
      dysfunction. On the other hand, seven of the nine patients with no trains also
      showed severe facial nerve dysfunction. CONCLUSIONS: The presence of high
      amplitude or high-frequency trains elicited by surgical manipulation to the
      facial nerve seems to indicate a critical situation for the facial nerve.
      However, certain types of mechanical trauma resulting in severe facial nerve
      paralysis cannot be identified by train responses.

PMID- 11449117
TI  - Displacement pattern of the normal pars flaccida in the gerbil.
AB  - OBJECTIVE: The aim of the current study was to assess the mechanical stiffness
      properties of the normal pars flaccida and to compare the results with those
      obtained in earlier studies on the pars tensa. BACKGROUND: Postinflammatory
      changes such as retraction pockets and cholesteatoma develop in the pars flaccida
      as well as in the pars tensa of the tympanic membrane. In these authors' previous
      experimental studies, stiffness changes are shown to develop early in the pars
      tensa in response to purulent otitis media and otitis media with effusion. These
      changes are suggested to be precursors to a later development of retraction
      pockets and cholesteatoma. In the clinical situation, retraction pockets are
      often found in the pars flaccida only. This study will establish the stiffness
      properties of the normal pars flaccida and form a base for forthcoming studies of
      the pars flaccida in response to otitis media with effusion and purulent otitis
      media, as well as retraction pocket formation and cholesteatoma. METHODS: A
      measure for the mechanical stiffness properties of the normal pars flaccida in
      the gerbil was assessed as its displacement for a given transtympanic pressure.
      The method used was moire interferometry, which is a noncontacting optical
      technique to measure the shape of the surface of an object. RESULTS: The
      displacement of the pars flaccida was a nonlinear and asymmetric function of
      pressure. The displacement per pressure unit rose steeply at low middle ear
      pressures to level out and reach a steady state at higher pressures. The
      displacement versus pressure characteristics for the pars flaccida strongly
      differed from those of the pars tensa. The pars tensa seemed more elastic.
      CONCLUSION: Reference values for displacement versus pressure characteristics of
      the normal gerbil pars flaccida were obtained using a moire interferometry
      method. The mechanical stiffness properties of the normal pars flaccida were
      strongly different from those of the pars tensa.

PMID- 11449118
TI  - Bilateral dehiscence of the superior semicircular canals.

PMID- 11449119
TI  - Cholesterol granuloma.

PMID- 11449121
TI  - [Hepatopathy in Still's disease in adults].

PMID- 11449122
TI  - [Who dies with hepatitis C virus in France?].
AB  - OBJECTIVES: To describe the characteristics of anti-HCV positive patients who
      have died in France. METHODS: Prospective study of deceased or transplanted anti
      HCV positive patients between January 1994 and February 1996, followed in
      Gastroenterology and Liver Units in 18 French General Hospitals. Retrospective
      study of patients with cirrhosis unrelated to HCV infection who died during the
      same period in 8 of these hospitals. RESULTS: Ninety-seven anti-HCV positive
      patients, 53 males and 44 females, deceased during the study period (except one
      transplanted patient), at a mean age of 67 (median: 71), from liver disease in
      79% of cases (all had cirrhosis, and 49 hepatocellular carcinoma). The supposed
      sources of infection were: blood transfusion (44%), intravenous drug use (10%),
      unknown (46%). All 27 patients (22 men) with a daily alcohol intake of 80 g or
      more had cirrhosis, and died an average of 10 years earlier. The anti-HVC
      negative patients with alcoholic cirrhosis who died were three times as numerous,
      and had similar characteristics to anti-VHC positive alcoholic patients.
      CONCLUSION: HCV-infected patients who die of liver disease lose 5 to 10 years of
      life expectancy, and 10 years more if they drink 80 g or more of alcohol daily.

PMID- 11449123
TI  - [Adult Still's disease: an unrecognized cause of acute febrile hepatic cytolysis.
      Study of twelve patients].
AB  - OBJECTIVE: Certain liver test abnormalities have been described in adult Still's
      disease. The objective of the present study was to analyze their type and
      frequency. PATIENTS: In a 10 year retrospective study, patients were included if
      they fulfilled Kahn's and/or Yamaguchi's diagnostic criteria (median follow-up:
      6.5 years). RESULTS: Twelve patients were selected. The median age was 25 years
      old and the sex ratio H/F was 2.7. Fever was present in 100% of patients and
      hepatomegaly in 41%. Liver test abnormalities were identified in 92% of patients:
      moderate cytolysis (level of transaminases between 2 and 5 N) (83%), severe
      cytolysis (level of transaminases > 5 N) (17%), cholestasis (elevated levels of
      GGT and/or alkaline phosphatase) (75%), and an increase in the LDH level (41%).
      All these liver abnormalities resolved spontaneously or during treatment (83%),
      within a median of 18 days. CONCLUSION: Our study confirms the high frequency of
      liver test abnormalities (> 2/3 of the patients) in adult Still's disease. These
      abnormalities are generally moderate and asymptomatic (3/4 of the cases), but
      severe cytolysis may exist. This emphasizes the need to consider a diagnosis of
      adult Still's disease in the presence of fever and elevated transaminase
      activity.

PMID- 11449124
TI  - [Lymphoproliferative disorders after liver transplantation].

PMID- 11449125
TI  - [Transanal endoscopic microsurgery: a forgotten minimally invasive technique].
AB  - OBJECTIVES: The aim of this study was to evaluate transanal endoscopic
      microsurgery in patients with benign and malignant rectal tumours with special
      reference to feasibility, morbidity, and recurrence rate. METHODS: Forty-three
      patients underwent transanal endoscopic microsurgical excision of rectal tumours
      between 1996 and 2000. The histological diagnosis was benign adenoma in 30 and
      invasive carcinoma in 13. The mean height of the tumour above the anal verge was
      11.2 +/- 3 cm and the mean diameter of the lesion was 3.4 +/- 1.5 cm. RESULTS:
      The mean operative time was 85 +/- 26 min and in one case (2%), it was necessary
      to convert to an anterior resection. The morbidity rate was 18%. Mean hospital
      stay was 3.9 +/- 2.4 days. Complete excision of the tumour with histological
      confirmation was achieved in 42 cases (98%). With a mean follow-up of 26 months,
      benign tumour recurrence was observed in one patient (3%). Of the 13 patients
      with carcinoma, two had immediate further radical resection. For the remaining 11
      patients, with a mean follow-up of 19 months, the recurrence rate was 75% for T2
      tumours and nil for T1 tumours. CONCLUSIONS: Transanal endoscopic microsurgery is
      safe and feasible technique which should have a useful place in the management of
      sessile adenomas of the mid and upper rectum. Its role in the management of
      rectal cancer is limited, although it may be appropriate for carefully selected
      cases.

PMID- 11449126
TI  - (13)CO(2) breath tests: comparison of isotope ratio mass spectrometry and non
      dispersive infrared spectrometry results.
AB  - BACKGROUND AND AIMS: Isotope ratio mass spectrometry is the standard analytical
      method for (13)CO(2) breath tests. The goal of this study was to compare the
      results of (13)CO(2) breath tests obtained by non dispersive infrared
      spectrometry, a new, simpler and cheaper method, with those obtained by the gold
      standard method. METHODS: Three hundred and eight patients were included: 150
      underwent a urea breath test for Helicobacter pylori diagnosis, 140 an
      aminopyrine breath test to measure liver function, and 18 an octanoic acid breath
      test for gastric emptying evaluation. A total of 750 breath samples were obtained
      in duplicate for isotope ratio mass and infrared spectrometry analyses. Breath
      test results were compared using Bland-Altman plots. RESULTS: The agreement
      between the two methods was excellent for urea breath tests (kappa
      coefficient=0.96), with only 3 discordant results. Although (13)C isotopic
      enrichment in breath was significantly lower with infrared spectrometry
      (P<0.0001), the agreement for the results of aminopyrine and octanoic acid breath
      tests was excellent. The clinical significance of these tests was similar for
      both methods. CONCLUSIONS: Infrared spectrometry results are comparable to
      isotope ratio mass spectrometry. Because this analytical method is simpler and
      less expensive, it could be used for clinical applications of (13)CO(2) breath
      tests.

PMID- 11449127
TI  - [Antitumoral immunotherapy and gastrointestinal tract: specific immunotherapy
      using dendritic cells and potential interest of heat shock proteins].

PMID- 11449128
TI  - [19th Meeting of the Digestive Epithelial Cell Study Group (CECED). Nimes,
      France, 25-26 January 2001. Abstracts].

PMID- 11449129
TI  - [Hepatobiliary cystic tumors. Clinical, radiological and histopathological study
      of 7 cases].
AB  - OBJECTIVES: Hepatobiliary cystic tumors are rare, but must be correctly diagnosed
      because of their potential malignancy. We report the clinical, radiological,
      pathological and evolutive characteristics of 7 cases of hepatobiliary cystic
      tumors. MATERIAL AND METHODS: Complete clinical charts were available.
      Radiological and pathological documents were reviewed. RESULTS: There were 4
      females and 3 males (median age, 58.7 yrs). In 3 cases, the presenting symptom
      was the palpation of a mass in the right upper abdominal quadrant. In 6 cases,
      pre-operative imaging studies showed a cystic intra-hepatic mass, containing
      vegetations and/or septa in 5 cases. In the remaining case, the radiological
      appearance showed a heterogeneous liver mass. Two patients were treated by
      pericystectomy and 5 by radical hepatectomy. At macroscopic examination, tumors
      were usually large (range: 2-24 cm) and multilocular. Histological diagnosis was:
      cystadenoma with mesenchymous stroma (2 cases), mucinous cystadenoma (2 cases),
      mucinous cystadenocarcinoma (2 cases), giant cell cystadenocarcinoma (1 case).
      The mean duration of follow up was 60 months. Two patients, both with
      cystadenocarcinomas, died after respectively, 21 and 34 months with metastatic
      dissemination. Five patients are alive without evidence of disease after a delay
      ranging from 14 to 144 months. CONCLUSION: Radical surgical treatment of cystic
      hepatobiliary tumors is necessary to obtain histopathological examination of the
      complete specimen, which is essential for a correct evaluation of the malignant
      potential of the lesion, and for prolonged survival, even in cases of locally
      invasive tumors.

PMID- 11449130
TI  - [Meningeal carcinomatosis in gastric cancer].
AB  - Meningeal carcinomatosis is an uncommon complication in patients with advanced
      gastric cancer. We report four cases of meningeal carcinomatosis occurring 18
      months (mean) after the diagnosis. The presenting manifestations were headache,
      visual troubles and seizure. Cytological cerebrospinal fluid (CSF) examination
      was the most useful diagnostic tool for leptomeningeal carcinomatosis,
      considering the normality of brain CT scan and MRI in our patients. Intrathecal
      methotrexate administration achieved a rapid improvement in neurological symptoms
      in all cases, but for a short 2-3 months duration. We conclude that survival
      improvement in advanced gastric cancer, due to chemotherapy, may allow emergence
      of unusual complications such as carcinomatous meningitis. This diagnosis should
      be evoked in the presence of unexplained neurologic symptoms and confirmed by CSF
      examination in order to propose a treatment and to delay serious neurologic
      disability and prolong survival.

PMID- 11449131
TI  - [Crohn's disease complicated by multiple and recurrent aseptic splenic
      abscesses].
AB  - We report a case of multiple aseptic splenic abscesses occurring in a woman with
      Crohn's disease for three years. All microbiological samples were negative. The
      diagnosis was suspected on abdominal echography and CT scan and confirmed on
      histologic examination of the splenectomy specimen. The evolution was marked by
      recurrence of fever and inflammatory syndrome, associated to transitory
      morphological abnormalities of the accessory spleen. Aseptic splenic abscesses
      recurrence was suspected. This case allows us to consider aseptic splenic
      abscesses as an extra-intestinal manifestation and not as a splenic localisation
      of Crohn's disease.

PMID- 11449132
TI  - [Correction of immune thrombocytopenia associated with hepatitis C virus
      infection after combination therapy with interferon alpha and ribavirin].

PMID- 11449133
TI  - [Severe acute hepatitis associated with ibuprofen treatment].

PMID- 11449134
TI  - [Prospective study of patient's perception of information before colonoscopy].

PMID- 11449135
TI  - [Granulomatous colitis likely induced by isotretinoin].

PMID- 11449136
TI  - [A misleading mistake in the colorectal carcinoma classification, in the French
      version of 'TNM Atlas', Springer edition].

PMID- 11449137
TI  - [Importance of small bowel transit in unexplained iron deficiency anemia after
      upper digestive endoscopy and colonoscopy].

PMID- 11449138
TI  - [Rectal mucosal lesions associated with Fleet-Phospho-soda].

PMID- 11449139
TI  - [Molecular basis of diagnosis in genetics].

PMID- 11449140
TI  - [Genetic counselling in Gastroenterology].

PMID- 11449141
TI  - [Diet, genetics and cancer].

PMID- 11449142
TI  - [Digestive polyposes: genetic aspects].

PMID- 11449143
TI  - [Clinical follow-up and treatment of patients with familial adenomatous
      polyposis].

PMID- 11449144
TI  - [Multiple endocrine neoplasia type 1: genetic and clinical aspects].

PMID- 11449145
TI  - [New chemotherapies for colorectal cancer treatment].

PMID- 11449146
TI  - [What are the validated indications for laparoscopy in digestive surgery?].

PMID- 11449147
TI  - [New inflammatory bowel disease drugs targeting the inflammatory cascade].

PMID- 11449148
TI  - [COX-2 specific inhibitors: are NSAIDs and the stomach become reconcilied?].

PMID- 11449149
TI  - [Percutaneous radiofrequency ablation of liver tumors].

PMID- 11449150
TI  - [Recent advances in treatment of anal diseases (except Crohn's disease)].

PMID- 11449151
TI  - [Auto-immune biliary diseases].

PMID- 11449152
TI  - [Mitochondrial liver diseases].

PMID- 11449153
TI  - [Hepatitis C virus and immune response].

PMID- 11449154
TI  - [Chronic viral hepatitis C: current therapy and perspectives].

PMID- 11449155
TI  - [Current knowledge on chronic hepatitis B therapy].

PMID- 11449156
TI  - [Hepatitis C virus and human immunodeficiency virus co-infection].

PMID- 11449157
TI  - [Hepatic pseudolesions].

PMID- 11449158
TI  - [Cystic lesions of the liver].

PMID- 11449159
TI  - [Imaging contribution in gastro-intestinal emergencies].

PMID- 11449160
TI  - [US and CT diagnosis of intestinal tumors].

PMID- 11449161
TI  - [[18F]-fluorodeoxyglucose scintigraphy in digestive cancer].

PMID- 11449162
TI  - [New developments in endoscopic diagnosis].

PMID- 11449163
TI  - [Breast cancer screening: a current topic].

PMID- 11449164
TI  - [MRI aspects of central nervous system sarcoidosis].
AB  - Sarcoidosis is a multisystemic disease of unknown origin characterized
      pathologically by the presence of noncaseating epithelioid granulomas.
      Symptomatic involvement of the CNS may develop in a patient with known
      sarcoidosis or it may be the initial manifestation. Intracranial sarcoidosis may
      include meningeal disease, cranial neuropathy, hypothalamic and pituitary
      dysfunction and both intraaxial and extraaxial mass. The MRI features are
      variable and non specific, so differentiation from other lesions (multiple
      sclerosis, tumour, meningitis, vasculitis) may be difficult, especially in the
      absence of extracranial disease. Patients with symptoms usually have
      corresponding CNS lesions at MR imaging, except for cranial nerves involvement.
      Under therapy, resolution of lesions at MR imaging lags behind resolution of
      clinical symptoms. MRI may contribute to confirm a clinically suspected diagnosis
      or detect subclinical involvement. MRI is also very helpful for follow-up under
      therapy.

PMID- 11449165
TI  - [Imaging of intraductal papillary mucinous tumor of the pancreas: literature
      review].
AB  - Intraductal papillary-mucinous tumor (IPMT) is defined as a syndrome consisting
      of dilatation of the main pancreatic duct and/or branch ducts associated with
      mucin overproduction. The purpose was to evaluate the usefulness of different
      imaging techniques (CT, EUS, ERCP) for determination of tumor invasion and
      pancreatic extension. Diagnosis often is delayed because it is confused with
      chronic pancreatitis or cystic neoplasms of the pancreas. It is difficult to rule
      out invasive malignancy. MRCP can be an essential imaging modality because it is
      a non-invasive technique. Intraductal ultrasound or pancreatoscopy could become
      in the future an additional useful preoperative procedure. A high frequency of
      invasive carcinoma in patients operated for pancreatic IPMT is observed. Surgical
      resection should be extended until a normal tissue margin is encountered.

PMID- 11449166
TI  - [3D reconstruction of microcalcification clusters].
AB  - PURPOSE: A characterization of the geometrical or morphological aspect of
      microcalcifications is not sufficient to confirm a diagnosis of cancer. On the
      other hand, it seems that the shape of the cluster is a pertinent and helpful
      criterion for diagnosis. The aim of our study is to work out a method for 3D
      reconstructions of clusters of microcalcifications. MATERIALS AND METHODS: After
      having tested different algorithms for extracting microcalcifications, we have
      developed a method of 3D reconstructions of the shape of the cluster from three
      radiographs. The technique, available using a standard mammography unit, consists
      of three principal steps RESULTS: The technique has been tested with two simple
      tridimensional phantoms and has given results with sufficient precision for
      possible clinical use. CONCLUSION: We plan now to apply the method in vivo with
      adaptation on a dedicated mammographic stereotactic unit with digital
      acquisition.

PMID- 11449167
TI  - [Impact of menopause hormone replacement therapy on screening mammography
      reading].
AB  - PURPOSE: To assess difficulties in reading screening mammographies related to
      hormone replacement therapy (HRT) in the setting of a breast cancer screening
      program. Disagreement between two readers is used as the assessment criterion.
      POPULATION AND METHODS: The study population consisted of all women participating
      in the ADEMAS breast cancer screening program in Bas-Rhin (France). Agreement
      between the two radiologists was considered when the same global conclusion (call
      back or not of the women for further examination) or the same conclusion for each
      of the nine possible lesions was observed. RESULTS: HRT is associated with a
      higher risk of disagreement between the two radiologists on global conclusion and
      on opacities. Conversely, disagreement risk is lowered for microcalcifications
      (whether benign or malignant) for HRT users. CONCLUSION: HRT is associated with a
      higher risk of disagreement on global conclusion. This has an impact on whether
      the women should be called-back or not according to reading of breast cancer
      screening program mammographies.

PMID- 11449168
TI  - [Prenatal semiology of diastematomyelia].
AB  - Diastematomyelia is a rare spinal malformation characterized by a division of the
      spinal cord. More often, the two hemicords are separated by a midline and
      sagittal osseous or fibrocartilaginous spur. In this report we describe two cases
      of diastematomyelia detected at routine second trimester detailed sonography and
      further assessed by MRI and spiral CT with surface shaded 3D-reconstructions. In
      addition to providing diagnosis, prenatal evaluation helps differentiate between
      diastematomyelia with good or bad prognosis.

PMID- 11449169
TI  - [Cross-sectional imaging of post endocarditis paravalvular myocardial abscesses
      of native mitral valves: 4 cases].
AB  - Four cases of submitral myocardial abscess imaged by CT or MRI following
      endocarditis are described. All cases occurred in fragile patients (diabetes
      mellitus, dialysis, severe cardiovascular diseases). An iatrogenic source was
      noted in one patient. Staphylococcus aureus was responsible in 2 patients. If
      subvalvular aortic abscesses are usually described, submitral myocardial
      abscesses are infrequent. In addition to transesophageal echocardiography, a
      technique superior to transthoracic echocardiography, CT and MRI may incidentally
      suggest the correct diagnosis. Both techniques provide useful morphological
      evaluation, information that can be used to optimize the timing for surgical
      repair.

PMID- 11449170
TI  - [Endovascular embolization of ophthalmic artery branches for control of
      refractory epistaxis: report of one case].
AB  - Embolization of the internal maxillary artery is an accepted method for control
      of severe or recurrent posterior epistaxis. Such endovascular treatment may fail
      if the vascular supply to the bleeding vessels originates in branches of the
      ophthalmic artery. We report one case in which embolization of the ophthalmic
      artery was performed to control epistaxis. Distal catheterisation at least beyond
      the second portion enables safe embolization.

PMID- 11449171
TI  - [Intramedullary metastases and syringomyelic cavities].
AB  - Intramedullary metastases from a non neurogenic cancer are relatively rare,
      representing approximately 1-2,1% of metastatic sites according to published
      autopsy reports. Their association with syrinx is extremely rare. Four cases have
      been described in the last 30 years. We report the case of a 60 year old female
      with past medical history of Peutz-Jeghers disease, who presented with clinical
      signs suggestive of medullary lesions of the cervical spine. MR imaging showed
      tumoral lesions at different levels associated with syrinx. Surgical biopsy
      confirmed the intramedullary lesions which, by pathology, were found to be of
      metastatic origin.

PMID- 11449172
TI  - [Multiple gastrointestinal tract duplication : a neonatal case report].
AB  - We report the case of newborn with multiple GI tract duplication cysts. Prenatal
      diagnosis was that of duodenal stenosis. A complete screening for
      polymalformative syndrome is required in the neonatal period and the authors
      insist on the importance of US and color Doppler US imaging.

PMID- 11449173
TI  - [Subcapsular hematoma of liver during pregnancy: report of 4 cases].
AB  - A Subcapsular hematoma of the liver is a rare but very serious complication of
      pregnancy. Diagnosis is confirmed at imaging (Ultrasound, CT, MRI) since clinical
      symptoms are not specific and biological signs have a delayed manifestation. The
      management of this complication depends on the integrity or rupture of Glisson's
      capsule. We report the cases of 4 patients and review of the literature.

PMID- 11449174
TI  - Upper extremities deep venous thrombosis: comparison of light reflection
      rheography and colour duplex ultrasonography for diagnosis and follow-up.
AB  - BACKGROUND: Non-invasive diagnosis of axillary-subclavian vein thrombosis or
      documentation of the post-thrombotic syndrome performing methods currently in use
      is not definitive. The purpose of this prospective study was to compare two
      methods for the diagnosis and follow-up of patients with primary and secondary
      axillary-subclavian vein thrombosis: light reflection rheography (LLR) which is a
      reflection of venous pressure changes in the extremity as record from the
      subdermal capillary plexus, and colour duplex ultrasonography (CDUS). METHODS: In
      36 patients with primary and secondary axillary-subclavian vein thrombosis were
      used a 4006 GE (Milwaukee, USA) colour duplex ultrasonography and an AV-1000
      Hemodynamics instrument for the light reflection rheography for diagnosis and
      follow-up. The LLR methodology that applied was simple, involving testing of the
      venous outflow in the upper extremities in response to exercise, and with
      normally respiratory variations of an open venous system that was also assessed
      by the non-invasive modalities. In the LLR application of venous congesting
      pressure, and measurement of the rate of venous outflow when the congesting
      pressure is released was also performed. RESULTS: Both methods were able to
      diagnose the axillary-subclavian thrombosis in the initial acute state. There
      were no cases of false-positive results in either method. The CDUS presented a
      lower sensitivity in comparison to LLR in the follow-up period of the patients. A
      positive study was confirmed by phlebography in each instance. CONCLUSIONS: The
      tracing obtained by LLR is easy to interpret and provides objective evidence of
      proximal venous occlusion. The test is easy to apply and the instrumentation is
      relatively inexpensive. Both LLR and CDUS, could prove to be an exciting
      development among non invasive diagnostic techniques for axillary-subclavian vein
      thrombosis, with major sensitivity of LLR in the follow-up.

PMID- 11449175
TI  - Serum lipoprotein(a) changes in acute myocardial infarction.
AB  - BACKGROUND: A strong correlation between high serum Lp(a) levels, a genetic
      modification of cholesterol-low density lipoproteins (c-LDL), and increased
      coronary heart disease rate has been found. Transient increased serum levels of
      this lipoprotein during acute myocardial infarction (AMI) and surgical
      interventions have been found. METHODS:  EXPERIMENTAL DESIGN: we assessed
      complete lipidic pattern in a study series composed of 19 patients with AMI. We
      also evaluated the changes of Lp(a) serum levels within the first week of the
      disease in order to assess whether a correlation between this parameter and
      extent of necrotic myocardial area is present. PATIENTS: study series was made up
      of 19 patients (13 males, 6 females; mean age 57.94+/-10.7 years) with AMI
      compared to 25 control subjects (12 males and 13 females; mean age 51.12+/-15.34
      years). MEASURES: we also withdrew a blood sample on days 1, 3 and 7 from the
      onset of the AMI. On the first day we evaluated the serum levels of the following
      parameters: glycaemia, azotemia, creatininemia, urycaemia, total cholesterol,
      high density lipoprotein cholesterol (c-HDL), low density lipoprotein cholesterol
      (c-LDL), triglycerides, fibrinogen, creatinphosphokinase, aspartate
      aminotranspherase, thromboplastine time and prothrombinic activity. Lp(a) has
      been evaluated on day 1, 3 and 7 and after 6 months from AMI. We performed an
      ultrasound scanning (US) of the heart in day 7 for evaluation of the extent of
      necrotic myocardial area by observation of "segmental kinetic area". RESULTS:
      Mean basal Lp(a) serum level was 28.94+/-29.78 mg/dl (as median 17), (normal
      values 0 to 25 mg/dl). This value was not changed on day 3 (mean 29.47+/-30.46
      mg/dl, median 18), while significantly increased on day 7 (39.84+/-42.77, median
      26, p=0.05). Spearman's rank correlation test showed a strong correlation between
      the increase of Lp(a) serum levels on day 7 and extent of necrotic myocardial
      area (r=0.696, p=0.001). CONCLUSIONS: The positive correlation between mean Lp(a)
      values on day 1 and 7, and the size of the necrotic area, suggest that Lp(a) has
      an atherogenic and prothrombotic role. Moreover, elevated Lp(a) values were
      related to greater tissue damage. We believe that periodical determination of
      Lp(a) values in subjects with coronary disease is useful in order to predict
      further acute vascular events.

PMID- 11449176
TI  - Clinical significance of normobasemia in early post-operative outcome of hepatic
      resections.
AB  - BACKGROUND: Major hepatic resections are usually followed by acid-base unbalance.
      Adjustment of the acid-base disorders is considered central when dealing with
      these critical patients and normobasemia is thought to be a favourable prognostic
      factor when occurring in the immediate postoperative outcome after major surgery.
      The present study was undertaken to investigate the influence of acid base
      balance on the early outcome after hepatic resection. METHODS: A series of fifty
      seven cirrhotic patients was submitted to liver resection for hepatocellular
      carcinoma. Forty-eight patients experienced an uneventful early postoperative
      outcome (CTR group). Nine died in the postoperative course (HD group). In all
      patients pulmonary, renal and hepatic functions were monitored pre- and
      postoperatively. The pH values were detected daily preoperatively and in the
      course of the first three days after hepatic resection. In the same days acid
      base balance and arterial ketone body ratio were assessed on arterial blood
      samples. Data were collected in a data base and statistical analysis was
      performed. RESULTS: A significantly higher metabolic alkalosis was found to
      characterize the first and second postoperative days (POD1 and POD2) in the CTR
      group (pH 7.43+/-0.007 vs pH 7.33+/-0.001; pH 7.45+/-0.006 vs pH 7.35+/-0.009;
      p<0.05). Lower values of pH and an associated impaired energetic status of the
      liver were found to characterise the postoperative course of the poor prognosis
      patients. At POD1 AKBR decreased in both groups but while recovering at POD2 in
      patients of CTR group maintained significantly lower values in HD group (AKBR 1+/
      0.3 vs 0.5+/-0.2; p<0.01). A lower energetic status of the liver is associated
      with an inadequate tricarboxylic acid cycle and is responsible for an impaired
      production of HCO3-. CONCLUSIONS: Apparent normobasemia is then expressive of
      liver failure leading to poor postoperative outcome.

PMID- 11449177
TI  - Helicobacter pylori seroprevalence in hepatitis C virus positive patients with
      cirrhosis. The Como cross-sectional study.
AB  - BACKGROUND: Liver cirrhosis is a significant cause of death in Italy and one of
      the most frequent causes of hospitalization. Acute peptic ulcer and upper
      gastrointestinal bleeding reportedly occur in over 15% of cirrhotic patients.
      Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic
      ulcer, we sought to ascertain the seroprevalence of H. pylori infection in
      cirrhotic patients. METHODS: In a cross-sectional study, we examined 52
      consecutive patients (31 female and 21 male, age range 54-82, mean 68.7 years)
      suffering from hepatitis C virus (HCV)-related cirrhosis attending the Unit of
      Gastroenterology of the Valduce Hospital of Como (Italy). RESULTS: The prevalence
      of antibodies against H. pylori was 86.5% (45/52) in the cirrhotics. Of female
      patients 28/31 (90.3%) were seropositive as compared to 17 of 21 (80.9%) of male
      patients. CONCLUSIONS: The very high prevalence of H. pylori infection may
      explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients.

PMID- 11449178
TI  - Role of hepatic resection in the treatment of hepatolithiasis.
AB  - BACKGROUND: The aim of the present study was to evaluate the safety and the
      efficacy of hepatic resection in the treatment of hepatolithiasis with
      intrahepatic biliary strictures. METHODS:  EXPERIMENTAL DESIGN: retrospective
      study. SETTING: University hospital, Italy. PATIENTS: 6 consecutive patients with
      single lobe hepatolithiasis operated on during the 4-year period 1994-98
      inclusive. INTERVENTIONS: major hepatic resections (3 left hepatectomies, 2 left
      lobectomies, 1 right hepatectomy). MAIN OUTCOME MEASURES: type and duration of
      the surgical procedure, intra/postoperative blood losses, intra/postoperative
      course and complications, pathology, and hepatolithiasis recurrence. RESULTS:
      Mean operative time was 3.34+/-0.02 hrs (range 3.0-4.3 hrs). Mean blood loss was
      233+/-150 ml (range 100-500 ml). No patient required intra/postoperative blood
      transfusions. No intraoperative complication was recorded. Mean postoperative
      hospitalization was 17+/-7 days (range 6-28 days). Postoperative course was
      uneventful in 4 (66%) cases. No postoperative mortality was recorded. One
      pancreatitis and 1 biliary fistula occurred, for an overall postoperative
      morbidity of 33%. Pathology showed cholangiocarcinoma in 2 cases (33%). During
      the follow-up period (range 3-48 months, mean 19.1+/-16.4 months), 1 patient had
      recurrent cholangitis due to right lobe lithiasis and 1 patient died for
      cholangiocarcinoma. CONCLUSIONS: Hepatic resection is the treatment of choice in
      patients with single lobe hepatolithiasis and unreversible biliary strictures or
      possible presence of cholangiocarcinoma. An early indication for surgery may
      reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.

PMID- 11449179
TI  - Lateral pelvic lymphadenectomy and total nerve sparing for locally advanced
      rectal cancer in Western patients.
AB  - BACKGROUND: In an attempt to improve the results of locally advanced rectal
      cancer treatment, we performed an extended surgical technique consisting of total
      mesorectal excision (TME), lateral pelvic lymphadenectomy (LPL) and total nerve
      sparing (NS). Resection of the autonomic nerves was realized only when these
      fibres were involved by the tumour. METHODS: Nine cases (9.2%) of a personal
      series of 98 western patients with rectal carcinoma operated on between January
      1992 and December 1997 at Third Department of Surgery, University La Sapienza,
      Rome, underwent TME, LPL and NS procedures for locally advanced extraperitoneal
      disease. RESULTS: Two out of seven patients in stage II/III suffered
      postoperatively from urinary retention with mild irregular flow as tested on
      urodynamics, but no long-term urinary disturbances persisted. Retrograde
      ejaculation occurred postoperatively in one of two patients who experienced
      urinary disturbances. Another patient had erection dysfunctions. These sexual
      dysfunctions did not improve during the long-term follow-up. Seven patients with
      stage II or stage III disease achieved a 5-year survival rate of 80.0% and a 5
      year disease-free survival rate of 68.6% after a mean follow-up period of 64.7
      months. None of them experienced local recurrence, but one patient died of
      diffuse metastatic disease 50 months after surgery. Two patients with stage IV
      rectal carcinoma died of local and distant disease 13 months and 35 months after
      operation. One patient underwent liver resection for solitary metastasis 25
      months after primary operation. CONCLUSIONS: TME, LPL, and NS with resection of
      autonomic nerves only when these fibres are involved by the disease can achieve
      satisfactory results in terms of survival and functional outcome in selected
      western patients with locally advanced rectal cancer.

PMID- 11449180
TI  - Impact of axillary level I and II lymphnode dissection on the therapy of stage I
      and II breast cancer.
AB  - BACKGROUND: Routine performance of axillary node dissection (AND) in the
      treatment of stage I and II breast cancer has become controversial because of
      pretended morbidity of this procedure and progressing consent for sentinel
      lymphadenectomy. METHODS: Ninety-four consecutive patients who underwent AND for
      clinical stage I and II breast cancer were evaluated for a range of 48.3 months
      after surgery for movement and sensory alterations and arm swelling. Arm
      circumference was measured in all patients at the same four sites on both the
      operated and non operated sides preoperatively and in the immediate and late
      postoperative course. Capacity for movement was assessed pre- and postoperatively
      as active ranging at the shoulder joint. Postoperative numbness and paresthesias
      were assessed by standard questions. RESULTS: No patient had axillary recurrence.
      None of the detected differences between the preoperative and postoperative arm
      circumferences reached statistical significance. No persistent motion limitation
      was observed. Pain, numbness, paresthesia were detected in almost all patients in
      the immediate postoperative period but resolved spontaneously in all cases within
      6 months. The obese body habit was detected on multivariate analysis as the only
      significant predictor of edema. CONCLUSIONS: No significant morbidity and no
      axillary recurrence were observed in current experience to follow AND. These
      findings suggest that axillary level I and II dissection remains an effective and
      safe tool for diagnostic, as well therapeutic, purposes in the treatment of stage
      I and II breast cancer. Further studies are necessary before it can safely be
      reported that axillary node dissection is an optional part of the treatment of
      stage I and II breast cancer.

PMID- 11449181
TI  - Clinical significance of the molecular detection of melanoma cells circulating in
      the peripheral blood in melanoma patients.
AB  - BACKGROUND: Blood circulating melanoma cells may be important for the spread of
      the disease. The current methods are not sensitive in detecting micro metastases.
      Tyrosinase mRNA can be detected in peripheral blood by a molecular test. As
      tyrosinase is expressed only in melanocytes and melanocytes normally do not
      circulate in the blood, the test may prove reliable in detecting circulating
      melanoma cells. METHODS:  EXPERIMENTAL DESIGN: we used a reverse-transcription
      polymerase chain reaction (RT-PCR) detecting tyrosinase mRNA in the blood. A
      prospective investigation in melanoma patients undergoing surgery was conducted;
      follow-up duration was 12 months. SETTING: University Department Laboratory and
      Melanoma Clinic of a Tertiary Hospital. PATIENTS: a total of 27 Greek patients
      with a diagnosis of malignant melanoma at different stages of the disease; 12
      months follow-up after surgery. Samples form 12 healthy volunteers and 13
      patients with chronic myelogenous leukemia served as controls. INTERVENTIONS:
      none. MEASURES: none. RESULTS: We detected mRNA tyrosinase in the peripheral
      blood in 16 out of 27 melanoma patients studied. No tyrosinase mRNA was detected
      in any of the 25 samples from the controls. Two of the 16 positive cases
      developed a metastasis within the next 12 months following testing. The other 14
      positive cases remain metastasis free for this period, as also did the test
      negative cases. CONCLUSIONS: Detection of blood circulating melanoma cells by a
      RT-PCR technique, may be helpful in defining melanoma patients who are at risk
      for the spread of the disease.

PMID- 11449182
TI  - Sexually and well-being in early menopause. Effect of transdermal estradiol
      therapy.
AB  - BACKGROUND: This study focus on the effect of 6 months transdermal estradiol
      therapy (TTS) on the sexual behaviour and the quality of life in early menopausal
      women, complaining of uncomfortable menopausal symptoms. METHODS: Three hundred
      and sixty-two postmenopausal women, aged 48-56, participated in this study. One
      hundred and seventy-one of them were given continuous solid matrix patch TTS 50
      mg/day for 6 months. Sexual behaviour, menopausal symptoms and well-being were
      evaluated through a self-rating method. We used a structured questionnaire with
      three obligatory answers (less/same/more) for each question--sexual life, hot
      flushes, touchiness, insomnia, blood pressure, work willing, memory loss, well
      being--filled in by the women themselves or by the medical equipe after a
      telephone interview. RESULTS: Seventy five per cent of women aged 51-53 and 84%
      aged 54-56, who had been treated for 6 months with TTS showed a fall of sexual
      drive, if compared with, respectively, 62% and 48% of untreated subjects. Relief
      of hot flushes, touchiness and insomnia occurred in 80% of treated women, with
      slight differences among the various groups while 61% showed increase of well
      being. CONCLUSIONS: The results of our study demonstrate that continuous TTS for
      6 months decreased sexual drive in 69% of women, improved menopausal symptoms in
      80% women but increased well-being only in 61% of women. These differences
      suggest that women's well-being does not seem linked only to the relief of
      menopausal symptoms and the impairment of their sexual life can play a negative
      role.

PMID- 11449183
TI  - HCV positivity at postmortem among 793 heroin addicts examined in Piedmont
      (Italy).
AB  - BACKGROUND: During a wider study in progress at the Turin University with the
      cooperation of the Departments of Anatomy, Pharmacology and Forensic Medicine,
      and of Biomedical Sciences and Human Oncology, anti-HCV antibodies were
      determined in the blood of drug-addicts submitted to judicial autopsy. METHODS:
      This investigation was carried out on blood samples taken at postmortem from 793
      subjects submitted to judicial autopsy in Piedmont from 1977 to 1996. This is a
      retrospective investigation and these cases represented 93.9% of the total
      autopsies, and 98.6% of them came from Turin and province. RESULTS: The
      percentage of subjects for whom the search for anti-HCV antibodies proved
      positive was 75.8% (74.5% among males, and 86.5% among females). These data
      remained relatively unchanged through the years, with a range 64.3% to 85.3%.
      They are close to those recorded in the international literature with regard to
      living subjects admitted to public health institutions for the prevention and
      treatment of drug addiction. CONCLUSIONS: As the positivity related to age, lower
      values were found among the 15-20-year olds as compared to the older ones: 57.1%
      among the former, and 85.5% among the latter. This difference may be due to a
      longer period of drug addiction among subjects deceased at an older age, with a
      more prolonged risk of infection.

PMID- 11449184
TI  - Breast cancer and obesity.
AB  - Epidemiological evidence links breast cancer, a typical endocrine-related tumor,
      with western lifestyle, in particular eating habits. Yet, it's necessary to
      distinguish premenopausal from postmenopausal breast cancer. Visceral obesity and
      body weight gain are considered responsible for the increased risk of
      postmenopausal breast cancer. In fact, the mammary gland is sensitive to the
      level of circulating estrogens, visceral obesity is usually associated with
      higher levels of free steroid hormones, and the adipose tissue performs important
      endocrine function (clearance and aromatisation of androgens, regulation of free
      testoterone/DHEAS molar ratio). Before menopause, ovarian polycystosis is often
      seen with android obesity, and breast cancer risk could arise; however, as
      visceral obesity is generally less frequent, genetic factors are more important
      than nutritional ones. Furthermore, variations have been recorded in the
      secretion of insulin and insulin-like growth factors, involved in the genesis of
      the breast cancer. High body weight and male fat distribution negatively
      influence prognosis of breast cancer, too; this association is linked with the
      presence of estrogen and progesterone receptors in tumoral cells. Links between
      diet quality and breast cancer risk are shown: increased use of saturated fats
      and animal proteins, and a consequently decreased use of vegetables, legumes and
      fruit, constituting the so-called Mediterranean diet, are considered responsible
      for the increased risk of breast cancer. Lower fat and alcohol ingestion, the use
      of dietary fibre and a higher use of complex carbohydrates could reduce breast
      cancer risk. Finally, starting from the results of our previous animal
      researches, we suggest using a tryptophan devoid diet for a few days for
      premenopausal women with male obesity and alterations to the menstrual cycle.

PMID- 11449185
TI  - Direct DNA analysis in a new Italian carrier of Hb-Belfast: beta 15 (A12) Trp-
      >Arg.
AB  - A young woman aged 21 was found to be a new carrier of Hb-Belfast: beta 15 (A 12)
      Trp-->Arg, and the characteristics of her hemoglobinopathy were not different
      from those of the four cases so far described: mild hemolysis with molecular
      instability of the abnormal Hb, red cells inclusion bodies, and slight
      alterations of some functional parameters of whole blood. On this occasion,
      direct DNA analysis indicated the genomic nucleotide replacement of the disease:
      TGG-AGG. This was inherited by the mother, originating from Bari (Apulia).

PMID- 11449186
TI  - Helicobacter pylori infection and coronary heart disease: a continuously debated
      question.

PMID- 11449188
TI  - "Analytical" or "synthetic" research in the life sciences.

PMID- 11449189
TI  - Thoughts on the film "The Matrix".

PMID- 11449190
TI  - Serum total testosterone is lower in men with Alzheimer's disease.
AB  - OBJECTIVES: The purpose of this study was to determine whether the level of serum
      total testosterone (TT) was different in cases of Dementia of the Alzheimer's
      Type (DAT) than in controls. SETTING AND DESIGN: We included 83 referred DAT
      cases and 103 cognitively screened volunteers (aged 75+/-9 years) from the Oxford
      Project To Investigate Memory and Ageing. METHODS: Information was obtained about
      potential confounds in the relation of DAT with testosterone, including age,
      gender, education, body mass index, smoking, (ab)use of alcohol, diabetes
      mellitus, endocrine therapy, and having undergone hysterectomy. TT was measured
      in non-fasting serum obtained between 10 and 12 a.m. using a competitive enzyme
      immunoassay. RESULTS: Men with DAT (n=39) had lower levels (p =0.005) of total
      serum testosterone (TT=14+/-5 nmol/L) than controls (n=41, TT=18+/-6 nmol/L).
      Lower TT was more likely in men with DAT, independent of potential confounds
      (Odds Ratio=0.78, 95% C.I.=0.68 to 0.91). In women there was no difference in TT
      levels between cases (n=44) and controls (n=62). MAIN FINDINGS: Our results
      suggested that low TT may be a co-morbid feature of DAT in men. However, low TT
      levels could also exacerbate the disease. CONCLUSIONS: Prospective longitudinal
      studies should investigate whether low TT levels precede or follow the onset of
      DAT (209 words).

PMID- 11449191
TI  - Changes in pineal sympathetic innervation are not significant in the
      hyperproliferative effects of pinealectomy on the intestinal crypts.
AB  - OBJECTIVES: To observe the effect of changes in the pineal sympathetic
      innervation on the crypt cell proliferation rate in the rat small intestine, and
      compare these with the effect of pinealectomy to determine the role of the
      sympathetic innervation in the effect of pinealectomy. METHODS: The effect of
      bilateral ablation of the superior cervical ganglion, and that of pinealectomy on
      the crypt cell proliferation rate in the rat small intestine was determined,
      using a stathmokinetic technique. RESULTS: Pinealectomy was associated with a
      considerably increased crypt cell proliferation rate, whereas superior cervical
      ganglionectomy was associated with a slightly decreased rate. CONCLUSIONS: It
      appears likely that changes in pineal melatonin production cannot be correlated
      directly with the effects of pinealectomy on the crypts, although melatonin
      production was not measured in this case. The role of loss of the non-adrenergic
      innervation of the pineal in the effect of pinealectomy needs to be examined.
      There is also other experimental evidence that melatonin-free extracts of the
      pineal, containing as yet unidentified substances, can influence mitotic activity
      in some tissues, so the possible role of these substances in the effects of
      pinealectomy should also be considered. Furthermore, the superior cervical
      ganglion itself has an extra-pineal role. Changes in pineal sympathetic
      innervation are not significant in the hyperproliferative effects of pinealectomy
      on the intestinal crypts.

PMID- 11449192
TI  - Melatonin inhibits spontaneous and oxytocin-induced contractions of rat
      myometrium in vitro.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of melatonin on
      spontaneous and oxytocin-induced contractility of pregnant and non-pregnant rat
      myometrium in vitro. DESIGN: Myometrial strips were removed from virgin or late
      pregnant (21 days gestation) Wistar rats following decapitation and placed in an
      organ bath containing Krebs' solution at 37 degrees C and pH 7.4, constantly
      bubbled with 95% oxygen-5% carbon dioxide and isometric contractions were
      recorded. Effects of cumulative concentrations of melatonin (0.1 to 10 microM) on
      spontaneous and oxytocin-induced contractions were studied. Possible involvement
      of Ca(2+)-activated K (+) channels in inhibitory actions of melatonin was
      investigated by using apamin (100 nM). RESULTS: Melatonin inhibited spontaneous
      and oxytocin-induced contractions of myometrium from both virgin and late
      pregnant rats in a dose-dependent manner. After inhibition of oxytocin-induced
      contractions by melatonin, application of prostaglandin F (2alpha) (1 microM) but
      not high KCl (30 mM) containing solution initiated contractile activity.
      Inhibitory response induced by melatonin (13 microM) was not affected by apamin
      (100 nM). CONCLUSIONS: Data from this study demonstrates that melatonin inhibits
      spontaneous and oxytocin-induced contractions of myometrium from pregnant and non
      pregnant rats. Although the exact mechanism is not clear, melatonin-induced
      inhibition of myometrial contractions may results from its interactions with
      Ca(2+) channels.

PMID- 11449193
TI  - Does leptin modulate immune and endocrine response in the time of LPS-induced
      acute inflammation?
AB  - OBJECTIVES: In many studies it has been reported, that leptin may play an
      important role not only in the regulation of food intake and body weight but can
      modify immune response. The aim of our study was to estimate the effects of the
      administration of exogenous leptin on serum concentration of proinflammatory
      cytokines (interleukin 6-IL 6 and tumor necrosis factor alpha-TNF alpha) and anti
      inflammatory cytokine (interleukin 10 - IL 10) during LPS induced acute
      inflammation. We also estimated leptin's influence on pituitary, thyroid, adrenal
      and gonadal hormones in response to lipopolysaccharide (LPS) induced acute
      inflammation. METHODS: Male rats Wistar-Kyoto were divided into four groups,
      which received respectively: placebo (0.9% NaCl), LPS, leptin and leptin with
      LPS. The TNF alpha and IL 6 serum concentrations were measured after 2 hours and
      IL 10 after 4 hours. The pituitary, thyroid, adrenal and gonadal hormones serum
      concentrations were measured after 2 and 4 hours. Cytokine concentrations were
      estimated using ELISA tests and hormones concentrations using RIA tests. RESULTS:
      Leptin did not have an effect on both cytokine responses (proinflammatory and
      anti-inflammatory) in the time of LPS-induced acute inflammation. Leptin enhanced
      LPS-induced increasing of corticosterone secretion after 2 hours and decreased
      LPS-induced inhibition of testosterone secretion after 4 hours. CONCLUSIONS:
      Leptin can modulate hormone response during LPS-induced acute inflammation.

PMID- 11449194
TI  - The hypothalamo-neurohypophysial response to melatonin.
AB  - The present paper reviews the findings accumulated on the role of pineal gland
      and its hormone - melatonin - in regulation of the hypothalamo-neurohypophysial
      system activity. Effects of modified photoperiod, pinealectomy or treatment with
      melatonin on the vasopressin and oxytocin biosynthesis and/or secretion have been
      described. Taken together, the in vivo and in vitro data suggest that the effect
      of melatonin on the vasopressin and oxytocin secretion depends on this pineal
      hormone concentration and experimental conditions.

PMID- 11449195
TI  - A review on cancer--psychospiritual status interactions.
AB  - With the advances in the knowledge of neuroimmunomodulation, a new era of
      investigations about the chemical basis of the state of mind has been initiated.
      Both emotions and states of spiritual consciousness may influence immune
      functions and cancer growth. Stress, anxiety and depressive states are associated
      with immunosuppression and enhanced frequency of tumors. On the other hand, the
      states of sexual pleasure and spiritual joy enhance the immune efficacy, by
      counteracting tumor onset and dissemination. The biochemistry of pleasure and
      immunostimulation is mainly mediated by pineal indoles and cannabinergic
      substances, whereas that of stress, anxiety and depression is associated with
      enhanced production of adrenal steroids, opioids and catecholamines. The sexual
      repression would allow a progressive immunosuppression through a profound damage
      in the biochemistry of pleasure. Therefore, a better definition of
      psychospiritual status-associated neuroimmunochemistry could allow us to improve
      the immune dysfunction by acting on the same neuroendocrine secretions which are
      involved in mediating the psychic influence on the immunity, including that
      against cancer.

PMID- 11449196
TI  - Effect of melatonin administration on activities of some lysosomal enzymes in the
      mouse.
AB  - OBJECTIVES: Changes in the activity of beta-glucuronidase, N-acetyl-beta
      glucosaminidase, cathepsin D and L, alanine aminopeptidase and lysosomal acid
      lipase in lysosomal fractions of the liver and kidneys of mice, which were
      administered 20 mg/kg b.w. of exogenous melatonin (N-acetyl-5-methoxytryptamine)
      for 7 and 14 days were investigated. METHODS: The slices of the liver and kidney
      were homogenized in 0.1M phosphate buffer, pH 7.0. Homogenates were subjected to
      differentiated centrifuging and determination of studied enzymes. RESULTS:
      Melatonin caused lowering of the activity of all the investigated lysosomal
      enzymes in the liver and kidney. CONCLUSION: Administration of melatonin was
      caused the lowering of the activity of the investigated lysosomal enzymes in
      comparison with values in control groups.

PMID- 11449197
TI  - Diurnal profile of melatonin concentrations in patients with major depression:
      relationship to the clinical manifestation and antidepressant treatment.
AB  - OBJECTIVES: The aim of the study was to establish if there are differences in the
      24-hour melatonin secretion profile between patients with major depression
      (before, and after treatment with clomipramine) compared to those in healthy
      subjects. Additionally, we determined if there are differences in melatonin
      concentrations, depending on the severity of depression, and the presence of 24
      hour rhythm disturbances. MATERIAL AND METHODS: Twenty patients with major
      depression and 24-hour rhythm disturbances, and 14 healthy volunteers took part
      in the study. Before, and after treatment with clomipramine all subjects had
      blood samples collected at 08:00, 14:00, 20:00, 24:00, 02:00, 04:00, and 08:00 h,
      for estimation of melatonin concentrations. Before and after treatment, the
      severity of depression was evaluated using the following scales: the Hamilton
      Depression Rating Scale (HADRS), Beck Depression Inventory (BDI), and clinical
      observation, as well as presence, and if so, severity of 24-hour rhythm
      disturbances were assessed. RESULTS: In individuals with major depression with
      marked disturbances of their diurnal rhythms, melatonin secretion is also
      disturbed, shown by the higher melatonin concentrations at night as compared to
      those in healthy individuals. However, melatonin levels were independent of the
      severity or the clinical manifestation of depression. Moreover, no correlation
      between the disturbances in their diurnal rhythms (sleep-watchfulness, diurnal
      mood shifts) and disturbed melatonin pattern was observed. CONCLUSIONS: Melatonin
      nocturnal concentrations in patients with major depression were higher than those
      in healthy individuals. However, the melatonin concentration values do not
      differentiate the patients in terms of the severity of the depressive symptoms.

PMID- 11449198
TI  - From the art director's desk.

PMID- 11449199
TI  - New perspectives on pediatric allergic rhinitis. Proceedings of a workshop.
      Barcelona, Spain.

PMID- 11449200
TI  - Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and
      diagnosis.
AB  - Allergic rhinitis (AR) is a heterogeneous disorder that despite its high
      prevalence is often undiagnosed. It is characterized by one or more symptoms
      including sneezing, itching, nasal congestion, and rhinorrhea. Many causative
      agents have been linked to AR including pollens, molds, dust mites, and animal
      dander. Seasonal allergic rhinitis (SAR) is fairly easy to identify because of
      the rapid and reproducible onset and offset of symptoms in association with
      pollen exposure. Perennial AR is often more difficult to detect than SAR because
      of the overlap with sinusitis, respiratory infections, and vasomotor rhinitis.
      SAR can result in hyperresponsiveness to allergens such as cigarette smoke, once
      pollen season is over. Perennial AR is defined as occurring during approximately
      9 months of the year. AR affects an estimated 20 to 40 million people in the
      United States alone, and the incidence is increasing; an estimated 20% of cases
      are SAR; 40% of cases are perennial rhinitis; and 40% of cases are mixed. The
      pathophysiology of SAR is complex. There is a strong genetic component to the
      allergic response, which is driven through mucosal infiltration and action on
      plasma cells, mast cells, and eosinophils. The allergic response occurs in two
      phases, which are considered the "early" and "late" phase responses. Early phase
      response occurs within minutes of exposure to the allergen and tends to produce
      sneezing, itching, and clear rhinorrhea; late phase response occurs 4 to 8 hours
      after allergen exposure and is characterized by congestion, fatigue, malaise,
      irritability, and possibly neurocognitive deficits. The key to diagnosis of AR is
      awareness of signs and symptoms. IgE antibody tests to detect specific allergens
      are the standard method used today; however, in addition, diagnosis must be
      confirmed with a positive history and demonstration that the symptoms are the
      result of IgE-mediated inflammation.

PMID- 11449201
TI  - Pediatric allergic rhinitis and comorbid disorders.
AB  - Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in
      the context of systemic allergic disease associated with numerous comorbid
      disorders, including asthma, chronic middle ear effusions, sinusitis, lymphoid
      hypertrophy with obstructive sleep apnea, disordered sleep, and consequent
      behavioral and educational effects. The coexistence of AR and asthma is complex.
      First, the diagnosis of asthma may be confounded by symptoms of cough caused by
      rhinitis and postnasal drip. This may lead to either inaccurate diagnosis of
      asthma or inappropriate assessment of asthma severity with over treatment of the
      patient. The term "cough variant rhinitis" is therefore proposed to describe
      rhinitis that manifests itself primarily as cough that results from postnasal
      drip. AR, however, also has a causal role in asthma; it appears both to be
      responsible for exacerbating asthma and to have a role in its pathogenesis.
      Postnasal drip with nasopharyngeal inflammation leads to a number of other
      conditions. Thus sinusitis is a frequent extension of rhinitis and is one of the
      most frequently missed diagnoses in children. Allergen exposure in the
      nasopharynx with release of histamine and other mediators can cause Eustachian
      tube obstruction possibly leading to middle ear effusions. Chronic allergic
      inflammation of the upper airway causes lymphoid hypertrophy with prominence of
      adenoidal and tonsillar tissue. This may be associated with poor appetite, poor
      growth, and obstructive sleep apnea. AR is therefore part of a spectrum of
      allergic disorders that can profoundly affect the well being and quality of life
      of a child. Prospective cohort studies are required to assess the disease burden
      caused by AR in childhood and to further assess the potential educational
      impairment that may result. Because AR is part of a systemic disease process, its
      management requires a coordinated approach rather than a fragmented, organ-based
      approach.

PMID- 11449202
TI  - Mode of action of intranasal corticosteroids.
AB  - The mode of action of intranasal corticosteroids (INCS) is complex. It is not
      known whether INCS penetrate the nasal mucosa or act on target cells; however,
      their low systemic activity supports the concept of local action on nasal mucosa.
      This local effect can nonetheless influence a variety of inflammatory cells and
      their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and
      Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent
      release of histamine is a possible but unproven mode of action. Epithelial cells
      are an important target for corticosteroids, and INCS concentration is high at
      the epithelial surface. INCS may combine with the corticosteroid receptors in
      epithelial cells, which are then expelled into the airway lumen together with the
      dead epithelial cells or migrating inflammatory cells. A reduced influx of
      mediator cells may explain some of the effects of INCS on rhinitis symptoms, but
      it cannot explain all of the effects because INCS also reduce the early-phase
      sneezing and rhinorrhea after an allergen challenge outside the pollen season. In
      this situation, the number of surface mast cells/basophils is very low, as it is
      in the absence of allergic rhinitis. The mechanism by which INCS treatment of
      allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic
      symptoms of an early-phase response involving mast cell release of histamine,
      remains to be determined. Studies should be conducted to characterize the broad
      range of mechanisms by which INCS produce their therapeutic effects in allergic
      rhinitis.

PMID- 11449203
TI  - Pharmacokinetics of intranasal corticosteroids.
AB  - Topical administration of corticosteroids can reduce the total dose of
      corticosteroid required to treat the patient and minimize side effects. This
      logic has led to the development of intranasal corticosteroids (INCS) for
      allergic and perennial rhinitis. The second generation of these compounds
      includes beclomethasone dipropionate, budesonide, flunisolide, fluticasone
      propionate, mometasone furoate, and triamcinolone acetonide. There is evidence
      that the INCS are effective in rhinitis; however, there is concern about the
      potential for these compounds to cause growth suppression. In one study,
      beclomethasone dipropionate significantly reduced growth in children; however,
      treatment of children with mometasone furoate nasal spray for 1 year showed no
      signs of growth suppression. It is evident that the differences among INCS lie in
      their pharmacokinetics. Structural differences among the various INCS influence
      their metabolism. The goal of INCS therapy is to have a high ratio of topical to
      systemic activity. The drug delivery device, absorption of the drug, and drug
      distribution all contribute to effective topical activity of an INCS. In
      addition, individual drug metabolism and elimination (half-life and drug
      clearance) also contribute to the therapeutic index of a drug. Overall, the
      second-generation INCS cause minimal systemic effects at recommended doses.

PMID- 11449204
TI  - Effects of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis
      in children.
AB  - In adults, morning plasma cortisol levels are twice that of late afternoon and
      evening values. In children, a delay in the time of onset in peak cortisol levels
      has been observed in those treated with inhaled corticosteroids. Consequently,
      the single morning cortisol level has a low sensitivity for detecting adrenal
      insufficiency in children. It is not clear which test is best for detection of
      clinically relevant hypothalamic-pituitary-adrenal (HPA) axis suppression in
      children; 24-hour plasma cortisol is a good test because it measures biologically
      active, free cortisol levels for the entire day and is noninvasive. For research
      purposes, the 24-hour integrated concentration plasma cortisol test is preferred.
      Studies that have looked at HPA axis suppression with intranasal corticosteroids
      indicate that overall, intranasal corticosteroids have minimal effect on the HPA
      axis. A review of the literature reveals one study in which there was a decreased
      output of urinary cortisol during treatment with either budesonide or fluticasone
      propionate in adults. Other studies of fluticasone propionate or budesonide have
      shown no effect on the HPA axis in children. Beclomethasone dipropionate was
      shown to affect urinary cortisol output in one study of healthy volunteers.
      However, in a long-term study in children, no effect on the HPA axis was found.
      Mometasone furoate has been extensively studied in more than 20 trials of adults
      and children. No effects on the HPA axis were detected in either children or
      adults. It is unlikely that children are more sensitive to corticosteroids than
      are adults. There seems to be little point in performing routine monitoring of
      adrenal function in children who are treated with intranasal corticosteroid
      treatment.

PMID- 11449205
TI  - Assessing the effect of intranasal steroids on growth.
AB  - Several studies have evaluated the effects of childhood use of corticosteroids on
      growth. In short-term studies, the budesonide (BUD) metered dose inhaler and
      methylprednisolone (injection) had significant effects on lower-leg growth,
      whereas terfenadine did not. When two doses of BUD (nasal inhaler, 200 or 400
      microg once daily) were compared with placebo, only the 400-microg dose had a
      significant effect on short-term growth. Intranasal mometasone furoate (MF) (100
      and 200 microg) had no significant effect on short-term lower-leg growth. In
      intermediate studies of 1-year duration, intranasal beclomethasone dipropionate
      (84 microg twice daily) significantly affected growth rate, whereas in a separate
      study, 100 microg intranasal MF once daily did not. Long-term growth data come
      from retrospective studies of children with asthma. In these studies, no
      significant effect on growth has been demonstrated in children taking inhaled
      beclomethasone dipropionate or BUD. The reason for the discrepancy between
      intermediate and long-term studies is unclear and warrants further study.
      Variables in childhood growth including seasonal variations may make growth
      difficult to assess. However, because growth suppression has been reported in
      children receiving inhaled or intranasal corticosteroids, the lowest effective
      dose of drug with a low systemic absorption ratio should always be used. Overall,
      there appears to be no growth suppression with 100 microg intranasal MF used once
      daily in children.

PMID- 11449206
TI  - Quality of life in adults and children with allergic rhinitis.
AB  - Quality of life, when referring to an individual's health, is called health
      related quality of life (HRQL). HRQL focuses on patients' perceptions of their
      disease and measures impairments that have significant impact on the patient.
      Similar symptoms may vary in their effect on different individuals; the goal of
      therapy should be to reduce impairments that patients consider important. HRQL
      can be measured with generic or specific questionnaires. Specific questionnaires
      may be more sensitive and are much more likely to detect clinically important
      changes in patients' impairments. Specific questionnaires used to assess HRQL in
      rhinitis are the Rhinoconjunctivitis Quality of Life Questionnaire, the
      Adolescent Rhinoconjunctivitis Quality of Life Questionnaire, and the Pediatric
      Rhinoconjunctivitis Quality of Life Questionnaire. HRQL issues in adult rhinitis
      patients include fatigue, decrease in energy, general health perception, and
      social function; impairment of HQRL generally increases with increasing degree of
      symptoms and severity of disease. In children, HRQL issues include learning
      impairment, inability to integrate with peers, anxiety, and family dysfunction.
      Comorbid disorders often associated with rhinitis, including sinusitis, otitis
      media, and frequent respiratory infections, can further compromise HRQL.
      Pharmacologic treatments can have both positive and negative effects on HRQL.
      Agents that have troublesome adverse effects such as sedation can have a negative
      impact, whereas nonsedating antihistamines and intranasal cortico-steroids can
      significantly improve HRQL in patients of all ages with rhinitis.

PMID- 11449207
TI  - Safety and efficacy of mometasone furoate aqueous nasal spray in children with
      allergic rhinitis: results of recent clinical trials.
AB  - Intranasal mometasone furoate (MF) has been extensively studied in adults and has
      been found to be safe and effective therapy for the treatment of allergic
      rhinitis. Several studies have now been conducted on pediatric patients. In all,
      990 pediatric patients given mometasone furoate nasal spray (MFNS) have been
      studied in phase I, II, and III clinical trials. In a dose-ranging study, 5 doses
      of nasal spray (25, 100, and 200 microg MFNS daily and 168 microg beclomethasone
      dipropionate daily) were compared with placebo. The 100- and 200-microg daily
      doses of MFNS were found to be more effective than 168 microg beclomethasone
      dipropionate or 25 microg MFNS given daily. MFNS (100 microg once daily) was
      chosen as the appropriate dose. In clinical efficacy and safety trials, MFNS was
      given to 381 patients 3 to 11 years of age for 4 weeks (357 patients received 100
      microg MFNS daily for 6 months) and was found to decrease symptom scores from
      baseline significantly better than placebo. The long-term safety of MFNS was also
      studied in 166 patients treated for one year; no significant changes in
      intraocular pressure were detected. Cosyntropin stimulation showed no decreases
      in cortisol. In adults, nasal mucosa showed improvement in appearance of
      epithelium and reduction of inflammatory infiltrates, and there were no signs of
      nasal atrophy.

PMID- 11449208
TI  - Corticosteroids in the treatment of pediatric allergic rhinitis.
AB  - The goal of treatment in pediatric allergic rhinitis is to provide effective
      prevention of or relief from allergic rhinitis symptoms as safely and effectively
      as possible. Removing or avoiding allergens is always advised; however,
      pharmacotherapy is often necessity. Pharmacologic options include systemic
      decongestants, which are associated with irritability and insomnia, particularly
      in children. Antihistamines are widely used; however, first-generation
      antihistamines are known to cause dry mouth and sedation. Oral corticosteroids
      are very effective but can have unwanted systemic effects. Over the past decade,
      intranasal corticosteroids have been shown to be the most effective form of
      pharmacologic treatment for allergic rhinitis. Data support the use of intranasal
      corticosteroids as first-line therapy over oral antihistamines; nonetheless, some
      clinicians have been reluctant to prescribe these agents, particularly for
      children, because of concerns for systemic effects. Overall, the newer
      corticosteroids, including mometasone furoate (MF), beclomethasone dipropionate,
      and budesonide have an improved risk-benefit ratio compared with older cortico
      steroids and are now considered the drug of choice for pediatric allergic
      rhinitis. A good deal of evidence exists that confirms the lack of systemic
      effects from intranasal cortico-steroids. However, reports of decreased bone
      growth in children receiving intranasal budesonide short-term and beclomethasone
      dipropionate long-term have heightened concerns that some of these drugs may have
      systemic effects. A new intranasal corticosteroid, MF nasal spray, has been
      studied in children 3 to 12 years of age and has been shown to be effective.
      Intranasal MF is available with once-daily dosing, which has the potential to
      decrease systemic side effects.

PMID- 11449209
TI  - Interactive relationships between hospital patients' noise-induced stress and
      other stress with sleep.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that hospital
      noise-induced subjective stress would interact with other subjective
      environmental and personal stress in a relationship with poorer patient sleep.
      METHODS: A secondary data analysis was done using correlations and hierarchical
      multiple regression. Ninety-seven cardiac patients participated after transfer
      from critical care to a general unit. The independent variables were assessed
      with Topf's 24-item Disturbance Due to Hospital Noise Scale and 5-point items for
      other environmental stress (ie, bed, lights) and personal stress (ie, pain,
      anxiety). Sleep was evaluated with the Verran and Snyder-Halpern Sleep Scale.
      RESULTS: Hierarchical multiple regression led to a multiple R of 0.435 (P <.01).
      An interaction term, subjective noise stress x subjective bed stress x subjective
      pain x subjective anxiety accounted for a significant amount of sleep variance
      (12%, F = 13.63, P =.000). Subjective bed stress x subjective pain accounted for
      an additional 5% (F = 6.4, P =.013). CONCLUSIONS: Studies using research designs
      that assess relationships between multiple patient stress variable interactions
      and sleep or other stress-related outcomes may produce more accurate results than
      studies on the independent effects of different types of stress.

PMID- 11449210
TI  - Characteristics, perceived stressors, and coping strategies of patients who
      experience neurally mediated syncope.
AB  - PURPOSE: The purpose of this study was to describe the characteristics, perceived
      stressors, and coping strategies of patients who experience neurally mediated
      syncope. METHODS: Qualitative and quantitative analyses of 65 medical records
      including both written records and videotaped interviews were performed.
      FINDINGS: The most frequently reported health problems were gastrointestinal
      disturbances (61.3%), mood disturbances (56.5%), headaches (53.2%), and chronic
      fatigue (47.4%). Risk for injury was high, with 54.1% of subjects indicating that
      they had an episode that resulted in a fall and 44.3% indicating that they had
      sustained an injury as a result of syncope. Distressing symptoms such as fatigue,
      dizziness, nausea, chest pain, headache, confusion, and dyspnea often persisted
      for hours or days after an episode of syncope. Coping strategies included
      limiting or changing activities and avoiding injury. CONCLUSIONS: Neurally
      mediated syncope is a disruptive, distressing disorder that is a source of
      significant disability. Comprehensive care should include a holistic assessment
      of the impact of the disorder and appropriate referrals or interventions for
      psychologic, social, and occupational issues.

PMID- 11449211
TI  - Knowledge, attitudes, and self-efficacy and compliance with medical regimen,
      number of emergency department visits, and hospitalizations in adults with
      asthma.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      knowledge, attitudes, and self-efficacy and compliance with prescribed medical
      regimen, number of emergency department (ED) visits, and hospitalizations in
      adults with asthma. METHOD: The sample consisted of 29 adults with a diagnosis of
      asthma. The relationship among knowledge, attitudes, self-efficacy, and
      compliance with medical regimen was explored through use of a survey design. The
      Knowledge, Attitude, and Self-Efficacy Asthma Questionnaire and the Asthma
      Management Questionnaire that measured compliance were mailed to subjects' homes.
      Once completed, questionnaires were returned, and demographic data and number of
      ED visits and hospitalizations were obtained through a retrospective chart
      review. RESULTS: There was a significant correlation between knowledge and
      attitudes and knowledge and self-efficacy. The more positive persons' attitudes
      toward their asthma, the higher their knowledge and self-efficacy scores. There
      were significant correlations between select demographic variables and knowledge,
      attitude, and self-efficacy. Women scored higher on attitudes, persons with a
      college education scored higher on knowledge and attitudes, and persons with mild
      asthma scored highest on the self-efficacy scale. Compliance with use of peak
      flow meters correlated with higher scores on the attitude and self-efficacy
      scales. The higher total compliance score group had significantly higher self
      efficacy scores. In addition, higher self-efficacy scores correlated with lower
      numbers of hospitalizations. CONCLUSION: Attitudes and self-efficacy rather than
      knowledge had the most significant impact on compliance and number of ED visits
      and hospitalizations. The Knowledge, Attitude, and Self-Efficacy Asthma
      Questionnaire provides a means for nurses to assess patients' knowledge,
      attitudes, and self-efficacy regarding their asthma. Patients with low scores
      could be channeled into programs that would help them improve their ability to
      manage their asthma.

PMID- 11449212
TI  - Use of complementary therapies, adherence, and quality of life in lung transplant
      recipients.
AB  - PURPOSES: The purpose of this study was to describe complementary and alternative
      medicine (CAM) use by lung transplant patients and to determine whether CAM users
      differ from nonusers with respect to health status, quality of life, or medical
      adherence. METHODS: A mailed survey seeking CAM, quality of life, and adherence
      information was sent to 145 lung transplant recipients, and 99 responded.
      RESULTS: The majority (88%) used at least 1 form of CAM (median, 2; range, 0-17).
      Prayer (68%), support groups (43%), and relaxation techniques (31%) were the most
      common. Only 44% of users reported discussing CAM with their providers. CAM users
      were adherent to their transplant regimen. Few differences were found between CAM
      users and nonusers. Education, high symptom burden, female sex, and depression
      symptoms were associated with various types of CAM use. CONCLUSION: Most lung
      transplant recipients are using CAM. Providers must explore potential for
      interaction or enhancement between CAM and standard therapy to optimize care.

PMID- 11449213
TI  - Effect of lateral positions on tissue oxygenation in the critically ill.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of lateral
      positions on tissue oxygenation in critically ill patients. DESIGN: The study
      design was prospective and quasi-experimental, and we used a convenience sample
      with random assignment. SETTING: The study took place in the intensive care unit
      and the cardiac intensive care unit of a 450-bed medical center in the
      northwestern United States. PATIENTS: The sample included 12 adult patients with
      indwelling pulmonary artery and radial arterial catheters who were receiving
      mechanical ventilation and who met the criteria of "critical illness" by having
      impaired arterial oxygenation (PaO2 < or = 70 mm Hg) and/or cardiac index < or =
      2.0 L/min/m2. OUTCOME MEASURES: The outcome measures were dependent variables
      reflecting oxygen delivery including heart rate, cardiac output, arterial oxygen
      content (CaO2) and oxygen consumption, and the adequacy of tissue oxygenation
      (serum lactate). INTERVENTION: Each patient was passively turned to each of the
      three positions (right and left 45 degrees lateral and supine) according to a
      computer-generated, randomized positioning sequence. Dependent variables were
      measured 15 minutes after each position change. No changes in ventilator settings
      or vasoactive drugs occurred during data collection. RESULTS: Analysis of
      variance for repeated measures was used in the data analysis. Post hoc analysis
      determined an effect size of 0.558 and power of 0.80 at an alpha level of.05. No
      statistically significant differences caused by position were found in mean CaO2,
      cardiac output, heart rate, respiratory rate, PaO2, SaO2, or lactate level.
      Pearson correlation analysis found no significant relationships between the
      primary variables reflecting oxygen delivery (cardiac output and CaO2) and serum
      lactate levels. CONCLUSIONS: These findings suggest that lateral positioning of
      critically ill patients who are hypoxemic or have low cardiac output does not
      further endanger tissue oxygenation. Evaluation of individual patient responses
      to position changes in the clinical setting is encouraged until further studies
      using more heterogenous populations can provide more definitive guidance.

PMID- 11449214
TI  - Deep vein thrombosis prophylaxis: the effectiveness and implications of using
      below-knee or thigh-length graduated compression stockings.
AB  - Potential complications of reduced mobility in both acute and chronically ill
      patients continue to challenge nurses on a daily basis. Deep vein thrombosis
      (DVT) is one of the most serious of these complications. Graduated compression
      stockings, also known as antiembolism stockings, are among the most commonly
      available and accepted methods of external compression for the prophylaxis of
      DVT. Currently, there are 2 lengths of graduated compression stockings in common
      use, thigh-length and below-knee. Although thigh-length stockings are widely
      perceived to be more effective in prophylaxis, difficulties associated with
      therapeutic application and maintenance are often encountered in different
      clinical settings. Below-knee stockings are easier to apply and maintain and
      appear to be tolerated better by patients. The aim of this article is to examine
      existing support for both lengths of stockings in terms of their effectiveness in
      DVT prophylaxis and to discuss the implications for practice.

PMID- 11449215
TI  - Atypical presentation of acute myocardial infarction in 3 age groups.
AB  - OBJECTIVE: The purpose of this study was to compare the clinical manifestations
      of first-time acute myocardial infarction (AMI) in 3 age groups of men and women
      who presented to the emergency departments of 3 acute tertiary care hospitals.
      DESIGN: An exploratory, descriptive design was used, and there were 2 phases to
      the project. Phase 1 was a retrospective chart audit of a systematic random
      sample of patient charts, and phase 2 included a structured interview of a
      prospective random sample of emergency and intensive care unit nurses and
      physicians. The data were collected by using a chart audit tool and a
      semistructured interview, respectively. SETTING: The study took place at a
      western Canada university affiliated with acute tertiary care centres. SAMPLE: A
      systematic random sample of 153 (105 men and 48 women) patient charts were
      audited from the health records departments of 3 acute care hospitals. All of the
      patients had experienced a first-time AMI. In addition, a random sample of
      emergency/intensive care unit nurses (n = 60) and physicians (n = 18) was
      interviewed. RESULTS: The results indicate that a statistically significant
      number of the oldest (75 years or older) male patients present with atypical
      manifestations of AMI compared with the men in the younger age groups (P =.005).
      The same trend was not noted for female patients. The results of the study are
      limited with respect to the small number of women in each age category. Caution
      must therefore be exercised in generalizing the results to the target population
      of women with AMI. The atypical manifestations are described. The results of the
      interviews revealed that many clinicians do not look for different clinical
      manifestations when assessing older patients. CONCLUSIONS: It is essential that
      nurses and physicians accurately assess patients with AMI, especially patients in
      the older age groups who may be presenting atypically. It is also important that
      professional and nonprofessional public health education initiatives include
      information regarding both typical and atypical presentation of AMI, particularly
      in the older patient.

PMID- 11449216
TI  - Relationship between psychosocial variables and compliance in patients with heart
      failure.
AB  - OBJECTIVE: The purpose of this study was to describe the socio-demographic,
      psychosocial, and social support variables that predict compliance to treatment
      regimens in HF patients. DESIGN AND SETTING: Semistructured interviews were
      conducted on 82 patients at an outpatient heart failure clinic to gather data
      related to compliance behaviors. Five standardized instruments were used to
      gather data on patients' psychosocial health status and perceived social support.
      RESULTS: The overall compliance rate was 85.13 (10.01%). Higher levels of
      compliance (> 90%) were noted for follow-up appointments, medications, smoking,
      and alcohol cessation. Poor compliance was observed with dietary and exercise
      recommendations (71% and 53%, respectively). In a multivariate model, higher
      education, higher mental and physical health status and neuroticism independently
      contributed to 24% of the variance in overall compliance. CONCLUSION: The study
      supports that HF patients had poor compliance with dietary and exercise regimens.
      Since following a dietary and exercise regimen has been demonstrated to reduce
      morbidity in this population, strategies to increase compliance should be
      rigorously pursued [corrected].

PMID- 11449217
TI  - Fear and anxiety in patients awaiting coronary artery bypass grafting.
AB  - OBJECTIVE: The purpose of this study was to identify the prevalence of fear and
      anxiety in patients awaiting coronary artery bypass grafting and the factors
      associated with high fear and high anxiety. DESIGN: The survey included 240
      patients placed on the waiting list for coronary artery bypass grafting at one
      hospital. SUBJECTS: Two hundred and seven patients completed the questionnaire.
      INSTRUMENTS: The Bypass Grafting Fear Scale, the State-Trait Anxiety Inventory,
      and the Hospital Anxiety and Depression Scale were used. RESULTS: Half of the
      patients experienced low fear and anxiety. Twenty-five percent had high fear, but
      only 5% had high anxiety. Patients who felt high fear were mainly women, had no
      vocational education, were on sick leave, were depressed, had a tendency towards
      anxiety, and had a short wait for operation. Patients who displayed medium or
      high anxiety were mostly under 55 years of age and had depression, but only low
      or no pain. CONCLUSIONS: The results facilitate better identification of
      predictors of high fear and anxiety as well as direct support and information for
      those patients.

PMID- 11449218
TI  - Cardiac instrument development in a low-literacy population: the revised Chest
      Discomfort Diary.
AB  - OBJECTIVE: The purpose of this study was to pilot test a self-administered chest
      pain questionnaire, a revised version of the Chest Discomfort Diary (CDD-R), in a
      sample of patients with chronic angina selected from a population known to have
      low literacy. DESIGN: The study design was descriptive and correlational. SAMPLE:
      The study used a convenience sample of 27 subjects with documented history of
      coronary artery disease and angina. Characteristics of the sample included a mean
      age of 56.3 years (SD, 12.4 years), 88.9% African-American, and 56.3% male, and
      59.3% had a history of acute myocardial infarction. Approximately 28% had
      achieved a 9th-grade education or less, and reading levels ranged from 4th grade
      to 12th grade. Subjects completed the CDD-R, a 36-item instrument reflecting
      multiple dimensions of anginal chest pain. RESULTS: Descriptions of the location
      (left chest, 66.6%), character (pressure, 59.2%), and precipitants of chest pain
      (walking, 51.8%) were consistent with clinical descriptions of "typical angina."
      Other physical symptoms such as shortness of breath (88.8%) and fatigue (85.1%)
      were reported. Walking (55.5%) was the activity most frequently described as
      difficult to perform because of chest pain, with sublingual nitroglycerin (77.7%)
      the most frequently used and most effective chest pain relief strategy.
      CONCLUSION: The CDD-R adequately measured multiple characteristics of anginal
      chest pain. Further research is needed to establish construct validity of the CDD
      R and to determine the feasibility of using the instrument to monitor changes
      over time in patients' chronic angina.

PMID- 11449219
TI  - Shooting the messenger.

PMID- 11449220
TI  - Genetics group targets disease markers in the human sequence.

PMID- 11449222
TI  - Europe hooks up with China for space first.

PMID- 11449223
TI  - Institutes prepare for pioneering bioinformatics work.

PMID- 11449224
TI  - Stem-cell fudge finds no favour with biologists.

PMID- 11449225
TI  - Bush plots raid on NIH funds to finance AIDS initiative.

PMID- 11449226
TI  - Royal Society disputes value of carbon sinks.

PMID- 11449227
TI  - Battle to save beleaguered beluga.

PMID- 11449228
TI  - UN backs transgenic crops for poorer nations.

PMID- 11449231
TI  - Consensus science, or consensus politics?

PMID- 11449232
TI  - Alien versus predator.

PMID- 11449233
TI  - Seeking, sometimes finding, that elusive chemistry.

PMID- 11449234
TI  - Researchers are popular, even if the industry is not.

PMID- 11449235
TI  - Time to shout about the benefits of chemistry.

PMID- 11449236
TI  - Singapore makes efforts to sustain biodiversity.

PMID- 11449237
TI  - Photos may offer clues over Ethiopian fossil site.

PMID- 11449238
TI  - Keeping Mendel in mind.

PMID- 11449244
TI  - Owen's Parthian shot.

PMID- 11449245
TI  - Phenomenal fluids.

PMID- 11449246
TI  - Lost City found.

PMID- 11449247
TI  - Cognitive neuroscience. Bold insights.

PMID- 11449249
TI  - High-energy physics. Disappearing dimensions.

PMID- 11449250
TI  - Palaeontology. Return to the planet of the apes.

PMID- 11449251
TI  - Planetary science. Saturn saturated with satellites.

PMID- 11449252
TI  - Apoptosis. Mostly dead.

PMID- 11449253
TI  - Nanotechnology. Less is more.

PMID- 11449254
TI  - Developmental biology. Vesicles and the spinal cord.

PMID- 11449255
TI  - Evolutionary biology. Autumn colour code.

PMID- 11449257
TI  - Obituary. Rosa Beddington (1956-2001).

PMID- 11449258
TI  - Sex-biased dispersal of great white sharks.

PMID- 11449259
TI  - Flame retardants. Persistent pollutants in land-applied sludges.

PMID- 11449260
TI  - Neuroadaptation. Incubation of cocaine craving after withdrawal.

PMID- 11449261
TI  - Neuropharmacology. Odorants may arouse instinctive behaviours.

PMID- 11449262
TI  - Cause of neural death in neurodegenerative diseases attributable to expansion of
      glutamine repeats.
AB  - Neurodegenerative diseases resulting from expanded repeat sequences of glutamine
      residues are associated with the formation of protein aggregates in the cell
      nuclei of the affected neurons, but whether these are pathogenic is
      controversial. Recent observations indicate that the ages of onset of these
      diseases are exponential functions of the repeat lengths and that the probability
      of neural death is constant with time. The only process known to us that could
      give rise to such behaviour is nucleation of the aggregates.

PMID- 11449263
TI  - An off-axis hydrothermal vent field near the Mid-Atlantic Ridge at 30 degrees N.
AB  - Evidence is growing that hydrothermal venting occurs not only along mid-ocean
      ridges but also on old regions of the oceanic crust away from spreading centres.
      Here we report the discovery of an extensive hydrothermal field at 30 degrees N
      near the eastern intersection of the Mid-Atlantic Ridge and the Atlantis fracture
      zone. The vent field--named 'Lost City'--is distinctly different from all other
      known sea-floor hydrothermal fields in that it is located on 1.5-Myr-old crust,
      nearly 15 km from the spreading axis, and may be driven by the heat of exothermic
      serpentinization reactions between sea water and mantle rocks. It is located on a
      dome-like massif and is dominated by steep-sided carbonate chimneys, rather than
      the sulphide structures typical of 'black smoker' hydrothermal fields. We found
      that vent fluids are relatively cool (40-75 degrees C) and alkaline (pH 9.0-9.8),
      supporting dense microbial communities that include anaerobic thermophiles.
      Because the geological characteristics of the Atlantis massif are similar to
      numerous areas of old crust along the Mid-Atlantic, Indian and Arctic ridges,
      these results indicate that a much larger portion of the oceanic crust may
      support hydrothermal activity and microbial life than previously thought.

PMID- 11449264
TI  - Neurophysiological investigation of the basis of the fMRI signal.
AB  - Functional magnetic resonance imaging (fMRI) is widely used to study the
      operational organization of the human brain, but the exact relationship between
      the measured fMRI signal and the underlying neural activity is unclear. Here we
      present simultaneous intracortical recordings of neural signals and fMRI
      responses. We compared local field potentials (LFPs), single- and multi-unit
      spiking activity with highly spatio-temporally resolved blood-oxygen-level
      dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest
      magnitude changes were observed in LFPs, which at recording sites characterized
      by transient responses were the only signal that significantly correlated with
      the haemodynamic response. Linear systems analysis on a trial-by-trial basis
      showed that the impulse response of the neurovascular system is both animal- and
      site-specific, and that LFPs yield a better estimate of BOLD responses than the
      multi-unit responses. These findings suggest that the BOLD contrast mechanism
      reflects the input and intracortical processing of a given area rather than its
      spiking output.

PMID- 11449265
TI  - A test of general relativity from the three-dimensional orbital geometry of a
      binary pulsar.
AB  - Binary pulsars provide an excellent system for testing general relativity because
      of their intrinsic rotational stability and the precision with which radio
      observations can be used to determine their orbital dynamics. Measurements of the
      rate of orbital decay of two pulsars have been shown to be consistent with the
      emission of gravitational waves as predicted by general relativity, but
      independent verification was not possible. Such verification can in principle be
      obtained by determining the orbital inclination in a binary pulsar system using
      only classical geometrical constraints. This would permit a measurement of the
      expected retardation of the pulse signal arising from the general relativistic
      curvature of space-time in the vicinity of the companion object (the 'Shapiro
      delay'). Here we report high-precision radio observations of the binary
      millisecond pulsar PSR J0437-4715, which establish the three-dimensional
      structure of its orbit. We see the Shapiro delay predicted by general relativity,
      and we determine the mass of the neutron star and its white dwarf companion. The
      determination of such masses is necessary in order to understand the origin and
      evolution of neutron stars.

PMID- 11449266
TI  - Discovery of water vapour around IRC+10216 as evidence for comets orbiting
      another star.
AB  - Since 1995, planets with masses comparable to that of Jupiter have been
      discovered around approximately 60 stars. These planets have not been seen
      directly, but their presence has been inferred from the small reflex motions that
      they gravitationally induce on the star they orbit; these motions result in small
      periodic wavelength shifts in the stellar spectrum. The presence of analogues of
      the smaller bodies in our Solar System cannot, however, be determined using this
      technique, because the induced reflex motions are too small-so an alternative
      approach is needed. Here we report the observation of circumstellar water vapour
      around the ageing carbon star IRC+10216; water is not expected in measurable
      quantities around such a star. The only plausible explanation for this water is
      that the recent evolution of IRC+10216, which has been accompanied by a
      prodigious increase in its luminosity, is causing the vaporization of a
      collection of orbiting icy bodies-a process considered in an earlier theoretical
      study.

PMID- 11449267
TI  - Discovery of 12 satellites of Saturn exhibiting orbital clustering.
AB  - The giant planets in the Solar System each have two groups of satellites. The
      regular satellites move along nearly circular orbits in the planet's orbital
      plane, revolving about it in the same sense as the planet spins. In contrast, the
      so-called irregular satellites are generally smaller in size and are
      characterized by large orbits with significant eccentricity, inclination or both.
      The differences in their characteristics suggest that the regular and irregular
      satellites formed by different mechanisms: the regular satellites are believed to
      have formed in an accretion disk around the planet, like a miniature Solar
      System, whereas the irregulars are generally thought to be captured
      planetesimals. Here we report the discovery of 12 irregular satellites of Saturn,
      along with the determinations of their orbits. These orbits, along with the
      orbits of irregular satellites of Jupiter and Uranus, fall into groups on the
      basis of their orbital inclinations. We interpret this result as indicating that
      most of the irregular moons are collisional remnants of larger satellites that
      were fragmented after capture, rather than being captured independently.

PMID- 11449268
TI  - Ion-beam sculpting at nanometre length scales.
AB  - Manipulating matter at the nanometre scale is important for many electronic,
      chemical and biological advances, but present solid-state fabrication methods do
      not reproducibly achieve dimensional control at the nanometre scale. Here we
      report a means of fashioning matter at these dimensions that uses low-energy ion
      beams and reveals surprising atomic transport phenomena that occur in a variety
      of materials and geometries. The method is implemented in a feedback-controlled
      sputtering system that provides fine control over ion beam exposure and sample
      temperature. We call the method "ion-beam sculpting", and apply it to the problem
      of fabricating a molecular-scale hole, or nanopore, in a thin insulating solid
      state membrane. Such pores can serve to localize molecular-scale electrical
      junctions and switches and function as masks to create other small-scale
      structures. Nanopores also function as membrane channels in all living systems,
      where they serve as extremely sensitive electro-mechanical devices that regulate
      electric potential, ionic flow, and molecular transport across cellular
      membranes. We show that ion-beam sculpting can be used to fashion an analogous
      solid-state device: a robust electronic detector consisting of a single nanopore
      in a Si3N4 membrane, capable of registering single DNA molecules in aqueous
      solution.

PMID- 11449269
TI  - Ordered nanoporous arrays of carbon supporting high dispersions of platinum
      nanoparticles.
AB  - Nanostructured carbon materials are potentially of great technological interest
      for the development of electronic, catalytic and hydrogen-storage systems. Here
      we describe a general strategy for the synthesis of highly ordered, rigid arrays
      of nanoporous carbon having uniform but tunable diameters (typically 6 nanometres
      inside and 9 nanometres outside). These structures are formed by using ordered
      mesoporous silicas as templates, the removal of which leaves a partially ordered
      graphitic framework. The resulting material supports a high dispersion of
      platinum nanoparticles, exceeding that of other common microporous carbon
      materials (such as carbon black, charcoal and activated carbon fibres). The
      platinum cluster diameter can be controlled to below 3 nanometres, and the high
      dispersion of these metal clusters gives rise to promising electrocatalytic
      activity for oxygen reduction, which could prove to be practically relevant for
      fuel-cell technologies. These nanomaterials can also be prepared in the form of
      free-standing films by using ordered silica films as the templates.

PMID- 11449270
TI  - The dating of shallow faults in the Earth's crust.
AB  - Direct dating of ductile shear zones and calculation of uplift/exhumation rates
      can be done using various radiometric dating techniques. But radiometric dating
      of shallow crustal faulting, which occurs in the crust's brittle regime, has
      remained difficult because the low temperatures typical of shallow crusted faults
      prevent the complete syntectonic mineral recrystallization that occurs in deeper
      faults. Both old (detrital) and newly grown (authigenic) fine-grained
      phyllosilicates are thus preserved in shallow fault zones and therefore their
      radiometric ages reflect a mixture of both mineral populations. Also, the loss of
      39Ar during neutron irradiation in dating of clay minerals can produce
      erroneously old ages. Here we present a method of characterizing the clay
      populations in fault gouge, using X-ray modelling, combined with sample
      encapsulation, and show how it can be used to date near-surface fault activity
      reliably. We examine fault gouge from the Lewis thrust of the southern Canadian
      Rockies, which we determine to be approximately 52 Myr old. This result requires
      the western North America stress regime to have changed from contraction to
      extension in only a few million years during the Eocene. We also estimate the
      uplift/exhumation age and sedimentary source of these rocks to be approximately
      172 Myr.

PMID- 11449271
TI  - Geology and palaeontology of the Late Miocene Middle Awash valley, Afar rift,
      Ethiopia.
AB  - The Middle Awash study area of Ethiopia's Afar rift has yielded abundant
      vertebrate fossils (approximately 10,000), including several hominid taxa. The
      study area contains a long sedimentary record spanning Late Miocene (5.3-11.2 Myr
      ago) to Holocene times. Exposed in a unique tectonic and volcanic transition zone
      between the main Ethiopian rift (MER) and the Afar rift, sediments along the
      western Afar rift margin in the Middle Awash provide a unique window on the Late
      Miocene of Ethiopia. These deposits have now yielded the earliest hominids,
      described in an accompanying paper and dated here to between 5.54 and 5.77 Myr.
      These geological and palaeobiological data from the Middle Awash provide fresh
      perspectives on hominid origins and early evolution. Here we show that these
      earliest hominids derive from relatively wet and wooded environments that were
      modulated by tectonic, volcanic, climatic and geomorphic processes. A similar
      wooded habitat also has been suggested for the 6.0 Myr hominoid fossils recently
      recovered from Lukeino, Kenya. These findings require fundamental reassessment of
      models that invoke a significant role for global climatic change and/or savannah
      habitat in the origin of hominids.

PMID- 11449272
TI  - Late Miocene hominids from the Middle Awash, Ethiopia.
AB  - Molecular studies suggest that the lineages leading to humans and chimpanzees
      diverged approximately 6.5-5.5 million years (Myr) ago, in the Late Miocene.
      Hominid fossils from this interval, however, are fragmentary and of uncertain
      phylogenetic status, age, or both. Here I report new hominid specimens from the
      Middle Awash area of Ethiopia that date to 5.2-5.8 Myr and are associated with a
      wooded palaeoenvironment. These Late Miocene fossils are assigned to the hominid
      genus Ardipithecus and represent the earliest definitive evidence of the hominid
      clade. Derived dental characters are shared exclusively with all younger
      hominids. This indicates that the fossils probably represent a hominid taxon that
      postdated the divergence of lineages leading to modern chimpanzees and humans.
      However, the persistence of primitive dental and postcranial characters in these
      new fossils indicates that Ardipithecus was phylogenetically close to the common
      ancestor of chimpanzees and humans. These new findings raise additional questions
      about the claimed hominid status of Orrorin tugenensis, recently described from
      Kenya and dated to approximately 6 Myr.

PMID- 11449273
TI  - Rapid and recent origin of species richness in the Cape flora of South Africa.
AB  - The Cape flora of South Africa grows in a continental area with many diverse and
      endemic species. We need to understand the evolutionary origins and ages of such
      'hotspots' to conserve them effectively. In volcanic islands the timing of
      diversification can be precisely measured with potassium-argon dating. In
      contrast, the history of these continental species is based upon an incomplete
      fossil record and relatively imprecise isotopic palaeotemperature signatures.
      Here we use molecular phylogenetics and precise dating of two island species
      within the same clade as the continental taxa to show recent speciation in a
      species-rich genus characteristic of the Cape flora. The results indicate that
      diversification began approximately 7-8 Myr ago, coincident with extensive
      aridification caused by changes in ocean currents. The recent origin of endemic
      species diversity in the Cape flora shows that large continental bursts of
      speciation can occur rapidly over timescales comparable to those previously
      associated with oceanic island radiations.

PMID- 11449274
TI  - Predators increase the risk of catastrophic extinction of prey populations.
AB  - There has been considerable research on both top-down effects and on disturbances
      in ecological communities; however, the interaction between the two, when the
      disturbance is catastrophic, has rarely been examined. Predators may increase the
      probability of prey extinction resulting from a catastrophic disturbance both by
      reducing prey population size and by changing ecological traits of prey
      individuals such as habitat characteristics in a way that increases the
      vulnerability of prey species to extinction. We show that a major hurricane in
      the Bahamas led to the extinction of lizard populations on most islands onto
      which a predator had been experimentally introduced, whereas no populations
      became extinct on control islands. Before the hurricane, the predator had reduced
      prey populations to about half of those on control islands. Two months after the
      hurricane, we found only recently hatched individuals--apparently lizards
      survived the inundating storm surge only as eggs. On predator-introduction
      islands, those hatchling populations were a smaller fraction of pre-hurricane
      populations than on control islands. Egg survival allowed rapid recovery of prey
      populations to pre-hurricane levels on all control islands but on only a third of
      predator-introduction islands--the other two-thirds lost their prey populations.
      Thus climatic disturbance compounded by predation brought prey populations to
      extinction.

PMID- 11449275
TI  - Essential role for Gab2 in the allergic response.
AB  - Dos/Gab family scaffolding adapters (Dos, Gab1, Gab2) bind several signal relay
      molecules, including the protein-tyrosine phosphatase Shp-2 and
      phosphatidylinositol-3-OH kinase (PI(3)K); they are also implicated in growth
      factor, cytokine and antigen receptor signal transduction. Mice lacking Gab1 die
      during embryogenesis and show defective responses to several stimuli. Here we
      report that Gab2-/- mice are viable and generally healthy; however, the response
      (for example, degranulation and cytokine gene expression) of Gab2-/- mast cells
      to stimulation of the high affinity immunoglobulin-epsilon (IgE) receptor
      Fc(epsilon)RI is defective. Accordingly, allergic reactions such as passive
      cutaneous and systemic anaphylaxis are markedly impaired in Gab2-/- mice.
      Biochemical analyses reveal that signalling pathways dependent on PI(3)K, a
      critical component of Fc(epsilon)RI signalling, are defective in Gab2-/- mast
      cells. Our data identify Gab2 as the principal activator of PI(3)K in response to
      Fc(epsilon)RI activation, thereby providing genetic evidence that Dos/Gab family
      scaffolds regulate the PI(3)K pathway in vivo. Gab2 and/or its associated
      signalling molecules may be new targets for developing drugs to treat allergy.

PMID- 11449276
TI  - The heparin-binding haemagglutinin of M. tuberculosis is required for
      extrapulmonary dissemination.
AB  - Tuberculosis remains the world's leading cause of death due to a single
      infectious agent, Mycobacterium tuberculosis, with 3 million deaths and 10
      million new cases per year. The infection initiates in the lungs and can then
      spread rapidly to other tissues. The availability of the entire M. tuberculosis
      genome sequence and advances in gene disruption technologies have led to the
      identification of several mycobacterial determinants involved in virulence.
      However, no virulence factor specifically involved in the extrapulmonary
      dissemination of M. tuberculosis has been identified to date. Here we show that
      the disruption of the M. tuberculosis or Mycobacterium bovis Bacille Calmette
      Guerin (BCG) hbhA gene encoding the heparin-binding haemagglutinin adhesin (HBHA)
      markedly affects mycobacterial interactions with epithelial cells, but not with
      macrophage-like cells. When nasally administered to mice, the mutant strains were
      severely impaired in spleen colonization, but not in lung colonization. Coating
      wild-type mycobacteria with anti-HBHA antibodies also impaired dissemination
      after intranasal infection. These results provide evidence that adhesins such as
      HBHA are required for extrapulmonary dissemination, and that interactions with
      non-phagocytic cells have an important role in the pathogenesis of tuberculosis.
      They also suggest that antibody responses to HBHA may add to immune protection
      against tuberculosis.

PMID- 11449277
TI  - Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling
      pathway.
AB  - The mouse open brain (opb) and Sonic hedgehog (Shh) genes have opposing roles in
      neural patterning: opb is required for dorsal cell types and Shh is required for
      ventral cell types in the spinal cord. Here we show that opb acts downstream of
      Shh. Ventral cell types that are absent in Shh mutants, including the floor
      plate, are present in Shh opb double mutants. The organization of ventral cell
      types in Shh opb double mutants reveals that Shh-independent mechanisms can
      pattern the neural tube along its dorsal-ventral axis. We cloned opb by a map
      based approach and found that it encodes Rab23, a member of the Rab family of
      vesicle transport proteins. The data indicate that dorsalizing signals activate
      transcription of Rab23 in order to silence the Shh pathway in dorsal neural
      cells.

PMID- 11449278
TI  - Phagocytosis promotes programmed cell death in C. elegans.
AB  - In the nematode Caenorhabditis elegans programmed cell death requires the killer
      genes egl-1, ced-4 and ced-3 (refs 1 and 2), and the engulfment of dying cells
      requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 (refs
      3,4,5). Here we show that engulfment promotes programmed cell death. Mutations
      that cause partial loss of function of killer genes allow the survival of some
      cells that are programmed to die, and mutations in engulfment genes enhance the
      frequency of this cell survival. Furthermore, mutations in engulfment genes alone
      allow the survival and differentiation of some cells that would normally die.
      Engulfment genes probably act in engulfing cells to promote death, as the
      expression in engulfing cells of ced-1, which encodes a receptor that recognizes
      cell corpses, rescues the cell-killing defects of ced-1 mutants. We propose that
      engulfing cells act to ensure that cells triggered to undergo programmed cell
      death by the CED-3 caspase die rather than recover after the initial stages of
      death.

PMID- 11449279
TI  - Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis
      elegans.
AB  - Genetic studies have identified over a dozen genes that function in programmed
      cell death (apoptosis) in the nematode Caenorhabditis elegans. Although the
      ultimate effects on cell survival or engulfment of mutations in each cell death
      gene have been extensively described, much less is known about how these
      mutations affect the kinetics of death and engulfment, or the interactions
      between these two processes. We have used four-dimensional-Nomarski time-lapse
      video microscopy to follow in detail how cell death genes regulate the extent and
      kinetics of apoptotic cell death and removal in the early C. elegans embryo. Here
      we show that blocking engulfment enhances cell survival when cells are subjected
      to weak pro-apoptotic signals. Thus, genes that mediate corpse removal can also
      function to actively kill cells.

PMID- 11449281
TI  - Decline and fall of the empire.
AB  - "Are they worlds, or are they mere masses of matter? Are physical forces alone at
      work there or has evolution begotten something more complex, something not unakin
      to what we know on Earth as life? It is in this that lies the peculiar interest
      of Mars." Percival Lowell (in ref. 1, p. 3)

PMID- 11449282
TI  - Mars' core and magnetism.
AB  - The detection of strongly magnetized ancient crust on Mars is one of the most
      surprising outcomes of recent Mars exploration, and provides important insight
      about the history and nature of the martian core. The iron-rich core probably
      formed during the hot accretion of Mars approximately 4.5 billion years ago and
      subsequently cooled at a rate dictated by the overlying mantle. A core dynamo
      operated much like Earth's current dynamo, but was probably limited in duration
      to several hundred million years. The early demise of the dynamo could have
      arisen through a change in the cooling rate of the mantle, or even a switch in
      convective style that led to mantle heating. Presently, Mars probably has a
      liquid, conductive outer core and might have a solid inner core like Earth.

PMID- 11449283
TI  - The crust and mantle of Mars.
AB  - Clues to the history of Mars are recorded in the chemistry and structure of the
      planet's crust and mantle. The mantle is the rocky, interior region of the planet
      that transports heat generated during accretion and subsequent core formation.
      The crust formed by melting of the upper mantle, and has been shaped and re
      distributed by impact, volcanism, mantle flow and erosion. Observations point to
      a dynamically active interior in the early phases of martian history, followed by
      a rapid fall-off in heat transport that significantly influenced the geological,
      geophysical and geochemical evolution of the planet, including the history of
      water and climate.

PMID- 11449284
TI  - Water and the martian landscape.
AB  - Over the past 30 years, the water-generated landforms and landscapes of Mars have
      been revealed in increasing detail by a succession of spacecraft missions. Recent
      data from the Mars Global Surveyor mission confirm the view that brief episodes
      of water-related activity, including glaciation, punctuated the geological
      history of Mars. The most recent of these episodes seems to have occurred within
      the past 10 million years. These new results are anomalous in regard to the
      prevailing view that the martian surface has been continuously extremely cold and
      dry, much as it is today, for the past 3.9 billion years. Interpretations of the
      new data are controversial, but explaining the anomalies in a consistent manner
      leads to potentially fruitful hypotheses for understanding the evolution of Mars
      in relation to Earth.

PMID- 11449285
TI  - Mars' volatile and climate history.
AB  - There is substantial evidence that the martian volatile inventory and climate
      have changed markedly throughout the planet's history. Clues come from areas as
      disparate as the history and properties of the deep interior, the composition of
      the crust and regolith, the morphology of the surface, composition of the present
      day atmosphere, and the nature of the interactions between the upper atmosphere
      and the solar wind. We piece together the relevant observations into a coherent
      view of the evolution of the martian climate, focusing in particular on the
      observations that provide the strongest constraints.

PMID- 11449286
TI  - Weather and climate on Mars.
AB  - Imagine a planet very much like the Earth, with similar size, rotation rate and
      inclination of rotation axis, possessing an atmosphere and a solid surface, but
      lacking oceans and dense clouds of liquid water. We might expect such a desert
      planet to be dominated by large variations in day-night and winter-summer
      weather. Dust storms would be common. Observations and simulations of martian
      climate confirm these expectations and provide a wealth of detail that can help
      resolve problems of climate evolution.

PMID- 11449287
TI  - Mars exploration.
AB  - An international flotilla of spacecraft are to be sent to Mars over the next
      decade in an effort to understand the planet's geology and climate history, and
      to determine whether some form of life ever started there. At least two
      spacecraft will be sent at each launch opportunity, and at times up to four
      spacecraft may be operating simultaneously at the planet.

PMID- 11449288
TI  - Mars outposts: a planetary society approach to exploration.

PMID- 11449289
TI  - Enhancing longevity of pacemakers through reprogramming. Underutilization and
      cost-effectiveness.
AB  - OBJECTIVE: This study was performed to observe the number of pacemakers that had
      never been reprogrammed after implantation, and the effect of optimised output
      programming on estimated longevity of pulse generators in patients with pacemaker
      METHODS: Sixty patients with Teletronics Reflex pacemakers were evaluated in a
      pacemaker clinic, from the time of the beginning of its activities, in June 1998,
      until March 1999. Telemetry was performed during the first clinic visit, and we
      observed how many pulse generators retained nominal output settings of the
      manufactures indicating the absence of reprogramming until that date. After
      evaluation of the capture threshold, reprogramming of pacemakers was performed
      with a safety margin of 2 to 2.5:1, and we compared the estimated longevity based
      on battery current at the manufacturer's settings with that based on settings
      achieved after reprogramming. RESULTS: In 95% of the cases, the original
      programmed setting was never reprogrammed before the patients attended the
      pacemaker clinic. Reprogramming the pacemaker prolonged estimated pulse generator
      life by 19.7+/-15.6 months (35.5%). CONCLUSION: The majority of the pacemakers
      evaluated had never been reprogrammed. Estimated pulse generator longevity can be
      prolonged significantly, using this simple, safe, efficacious, and cost-effective
      procedure.

PMID- 11449290
TI  - Establishing the prevalence of hypertension. Influence of sampling criteria.
AB  - OBJECTIVE: To compare the prevalence of systemic hypertension in two different
      populations: a representative sample of the adult urban population of Porto
      Alegre, and individuals who sought blood pressure measurement in a hypertension
      prevention and control campaign. METHODS: A cross-sectional study was carried out
      involving a representative sample of the adult urban population of Porto Alegre
      and a population sample obtained from a hypertension prevention and control
      campaign, which included all the individuals who sought the blood pressure
      assessment unit at the Hospital das Clinicas in Porto Alegre. The following
      parameters were investigated: history of hypertension, use of antihypertensive
      drugs, age, and sex. Adjustments for age and sex in the prevalence rates were
      performed to make them comparable. RESULTS: Hypertension prevalence, defined as
      values > or =160/95 mmHg or treatment with antihypertensive drugs, was higher in
      the campaign sample (42%) as compared with the population sample (24%). Among
      those who were aware of their hypertensive condition and were under medication,
      54% of the campaign sample and 62% of the representative population sample
      maintained their pressure levels <160/90 mmHg. CONCLUSION: Prevalence rates of
      hypertension differed a lot in the campaign sample and in the representative
      population sample, showing that the sampling criterion may influence assessment
      of risk factors and bias the association between risk factors and health
      aggravations.

PMID- 11449291
TI  - Clinical impact of transesophageal echocardiography in patients with stroke
      without clinical evidence of cardiovascular sources of emboli.
AB  - OBJECTIVE: The purpose of this study is to evaluate the impact of transeophageal
      echocardiography on management of patients at low-risk for cardiogenic embolism
      to prevent new potential cardiovascular sources of emboli. METHODS: We studied 69
      patients with ischemic stroke at low-risk for cardiogenic embolism.
      Transeophageal echocardiography was performed to access: left atrium enlargement;
      communication or aneurysm of the interatrial septum; patent foramen ovale;
      spontaneous echo contrast or intracavitary thrombi; the presence of intraaortic
      atherosclerotic plaques or thrombi; significant valvar morphologic alteration or
      dysfunction; left ventricle enlargement, hypertrophy, or contractile abnormality.
      Transesophageal echocardiography altered clinical management, and we adopted
      anticoagulant therapy or another procedure apart from the use of acetylsalicylic
      acid. RESULTS: Transeophageal echocardiography detected at least one abnormality
      in 40 cases (58%). Clinical conduct was adjusted after the performance of
      transesophageal echocardiography in 11 patients (15.9%); anticoagulation was
      added in 10 cases and surgical correction in one patient. CONCLUSION:
      Transeophageal echocardiography was a very useful tool in the secondary
      prevention for stroke in patients at low risk for cardiogenic embolism.

PMID- 11449292
TI  - Diet and medication in the treatment of hyperuricemia in hypertensive patients.
AB  - OBJECTIVE: To evaluate the effects of diet and medication, either isolated or
      associated, on serum levels of uric acid in patients with hyperuricemia. METHODS:
      We studied patients from the Hypertension Unit of the University of Goias who had
      hyperuricemia (men > or =8.5 mg/dL and women > or =7.5 mg/dL). We divided the
      patients into three groups: G1 (low purine diet), G2 (low purine diet +
      medication), and G3 (medication only). Patients received allopurinol, 150 mg/day
      titrated up to 300 mg/dL when necessary. Patients were evaluated with regards to
      their lifestyles (diet, smoking, physical, activity, alcohol consumption), uric
      acid, blood pressure, use of medication, body mass index, cholesterol, and
      triglyceride. Follow-up took place in weeks 0 (M1), 6 (M2), 12 (M3) during the
      intervention and in week 36 (M4) after the study was completed. RESULTS: Fifty
      five patients participated in the study, 31 women, mean age 54.4+/-10.6 years,
      body mass index 28.6+/-3.9 kg/m2. A similar reduction (p<0.001) in uric acid
      levels occurred in the three intervention groups. In week 36 (M4), after 24 weeks
      without intervention, a tendency toward elevation of uricemia was noted in G2 and
      G3, and a continuous drop in uricemia was noted in G1. No significant
      modifications were observed in the other variables analyzed. CONCLUSION:
      Considering the cost x benefit relationship, a diet low in purine should be the
      1st therapeutic option for controlling hyperuricemia in patients with similar
      characteristic to the ones presented in this study.

PMID- 11449293
TI  - Influence of the echocardiographic score and not of the previous surgical mitral
      commissurotomy on the outcome of percutaneous mitral balloon valvuloplasty.
AB  - OBJECTIVE: To evaluate prior mitral surgical commissurotomy and echocardiographic
      score influence on the outcomes and complications of percutaneous mitral balloon
      valvuloplasty. METHODS: We performed 459 complete mitral valvuloplasty
      procedures. Four hundred thirteen were primary valvuloplasty and 46 were in
      patients who had undergone prior surgical commissurotomy. The prior
      commissurotomy group was older, had higher echo scores, and a tendency toward a
      higher percentage of atrial fibrillation. RESULTS: When the groups were compared
      with each other, no differences were found in pre- and postprocedure mean
      pulmonary artery pressure, mean mitral gradient, mitral valve area, and mitral
      regurgitation. Because we found no significant differences, we subdivided the
      entire group based on echo scores, those with echo scores < or =8 and those with
      echo scores >8 the mitral valve area being higher in the < or =8 echo score group
      2.06+/-0.42 versus 1.90+/-0.40 cm2 (p=0.0090) in the >8 echo score group.
      CONCLUSION: Dividing the groups based on echo score revealed that the higher echo
      score group had smaller mitral valve areas postvalvuloplasty.

PMID- 11449294
TI  - The use of primary stenting or balloon percutaneous transluminal coronary
      angioplasty for the treatment of acutely occluded saphenous vein grafts. Results
      from the Brazilian National Registry--CENIC. Central Nacional de Intervencoes
      Cardiovasculares.
AB  - OBJECTIVE: We conducted a comparative analysis of the in-hospital outcomes of
      patients who underwent primary percutaneous transluminal angioplasty (PTCA) or
      stent implantation because of an acute myocardial infarction (AMI) related to an
      acute vein graft occlusion. METHODS: Since 1991 the Brazilian Society of
      Hemodynamic and Interventional Cardiology has maintained a large database
      (CENIC). From these, we selected all consecutive patients, who underwent primary
      PTCA or stenting in the first 24 hours of AMI, with the target vessel being an
      occluded vein graft. Immediate results and major coronary events occurring up
      until hospital discharge were analyzed. RESULTS: During this period, 5,932
      patients underwent primary PTCA or stenting; 158 (3%) of the procedures were
      performed because of an acute vein graft occlusion. Stenting was performed in 74
      (47%) patients. Patients treated with stents had a higher success rate and lower
      mean residual stenosis compared with those who underwent primary balloon PTCA.
      The incidence of reinfarction and death were similar for stenting and balloon
      PTCA. CONCLUSION: Primary percutaneous treatment of AMI related to acute vein
      graft occlusion is still an uncommon practice. Primary stenting improved luminal
      diameter and offered higher rates of success; however, this strategy did not
      reduce the in-hospital reinfarction and death rate, compared with that occurring
      with PTCA treatment.

PMID- 11449295
TI  - Trends in death from circulatory diseases in Brazil between 1979 and 1996.
AB  - OBJECTIVE: To analyze the trends in mortality due to circulatory diseases in men
      and women aged > or =30 years in Brazil from 1979 to 1996. METHODS: We analyzed
      population count data obtained from the IBGE Foundation and mortality data
      obtained from the System of Information on Mortality of the DATASUS of the
      Ministry of Health. RESULTS: Circulatory diseases, ischemic heart disease, and
      cerebrovascular disease were the major causes of death in men and women in
      Brazil. The standardized age coefficient for circulatory disease in men aged > or
      =30 years ranged from 620 to 506 deaths/100,000 inhabitants and in women from 483
      to 383 deaths/100,000 inhabitants for the years 1979 and 1996, respectively. In
      men, the mean coefficient for the period was 586.25 deaths with a significant
      trend towards a decrease (P<0.001) and a decline of 8.25 deaths/year. In women,
      the mean coefficient for the period was 439.58 deaths, a significant trend
      towards a decrease (P<0.001) and a rate of decline of 7.53 deaths/year. The same
      significant trend towards a decrease in death (P<0.001) was observed for ischemic
      heart disease and cerebrovascular disease. Risk of death from these causes was
      always higher for men of any age group (P<0.001). Cerebrovascular disease was the
      primary cause of death in women. CONCLUSION: Although circulatory diseases have
      been the major cause of mortality in men and women in the Brazilian population,
      with a greater participation by cerebrovascular diseases, a trend towards a
      decrease in the risk of death from these causes is being observed.

PMID- 11449296
TI  - Double-outlet left ventricle. Echocardiographic diagnosis.
AB  - This is a case report of a double-outlet left ventricle associated with tricuspid
      atresia and hypoplasia of the right ventricle, diagnosed during echocardiography
      with color-flow imaging, in a three-month-old child who presented with fatigue
      and cyanosis. The child underwent palliative pulmonary arterial banding without
      an invasive procedure, and showed sustained improvement during follow-up.

PMID- 11449297
TI  - Twenty-year-old woman with pulmonary hypertension, syncope, and severe headache.

PMID- 11449298
TI  - [Clinical-radiographic correlation - Case 6/2001 - Instituto do Coracao do
      Hospital das Clinicas da FMUSP].

PMID- 11449299
TI  - Noninvasive diagnostic evaluation for chest pain in women.

PMID- 11449300
TI  - The brain decade in debate: IV. Chronobiology.
AB  - The present article is the adapted version of an electronic symposium organized
      by the Brazilian Society of Neuroscience and Behavior (SBNeC) which took place on
      June 14, 2000. The text is divided into three sections: I. The main issues, II.
      Chronodrugs, and III. Methods. The first section is dedicated to the perspectives
      of chronobiology for the next decade, with opinions about the trends of future
      research being emitted and discussed. The second section deals mostly with drugs
      acting or potentially acting on the organism's timing systems. In the third
      section there are considerations about relevant methodological issues concerning
      data analysis.

PMID- 11449301
TI  - Extracellular matrix molecules as targets for brown spider venom toxins.
AB  - Loxoscelism, the term used to describe lesions and clinical manifestations
      induced by brown spider's venom (Loxosceles genus), has attracted much attention
      over the last years. Brown spider bites have been reported to cause a local and
      acute inflammatory reaction that may evolve to dermonecrosis (a hallmark of
      envenomation) and hemorrhage at the bite site, besides systemic manifestations
      such as thrombocytopenia, disseminated intravascular coagulation, hemolysis, and
      renal failure. The molecular mechanisms by which Loxosceles venoms induce injury
      are currently under investigation. In this review, we focused on the latest
      reports describing the biological and physiopathological aspects of loxoscelism,
      with reference mainly to the proteases recently described as metalloproteases and
      serine proteases, as well as on the proteolytic effects triggered by L.
      intermedia venom upon extracellular matrix constituents such as fibronectin,
      fibrinogen, entactin and heparan sulfate proteoglycan, besides the disruptive
      activity of the venom on Engelbreth-Holm-Swarm basement membranes. Degradation of
      these extracellular matrix molecules and the observed disruption of basement
      membranes could be related to deleterious activities of the venom such as loss of
      vessel and glomerular integrity and spreading of the venom toxins to underlying
      tissues.

PMID- 11449302
TI  - The DNA puff BhB10-1 gene is differentially expressed in various tissues of
      Bradysia hygida late larvae and constitutively transcribed in transgenic
      Drosophila.
AB  - We extended the characterization of the DNA puff BhB10-1 gene of Bradysia hygida
      by showing that, although its mRNA is detected only at the end of the fourth
      larval instar, BhB10-1 expression is not restricted to the salivary gland, the
      tissue in which this gene is amplified. Different amounts of BhB10-1 mRNA were
      detected in other larval tissues such as gut, Malpighian tubules, fat body, brain
      and cuticle, suggesting that this gene is expressed differentially in the various
      tissues analyzed. Analysis of transgenic Drosophila carrying the BhB10-1
      transcription unit and flanking sequences revealed that the tested fragment
      promotes transcription in a constitutive manner. We suggest that either cis
      regulatory elements are missing in the transgene or factors that temporally
      regulate the BhB10-1 gene in B. hygida are not conserved in Drosophila.

PMID- 11449303
TI  - Lack of mutations of exon 2 of the MEN1 gene in endocrine and nonendocrine
      sporadic tumors.
AB  - In addition to the mutations that underlie most cases of the multiple endocrine
      neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also
      been described in sporadic tumors like gastrinomas, insulinomas and bronchial
      carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations
      have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was
      obtained by phenol/chloroform extraction and ethanol precipitation from 92
      formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue
      samples. We used 5 pairs of primers to encompass the complete coding sequence of
      exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single
      stranded conformation polymorphism (PCR-SSCP) technique in 78 sporadic thyroid
      cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular
      carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal
      lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2
      pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma) and 24 breast cancers
      (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors). The PCR
      product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct
      sense and antisense sequencing did not identify mutations. These results suggest
      that the MEN1 gene is not important in breast, thyroid or adrenal sporadic
      tumorigenesis. Because the frequency of mutations varies significantly among
      tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid
      and adrenal cancers, another tumor suppressor gene residing in this region is
      likely to be involved in the tumorigenesis of these neoplasms.

PMID- 11449304
TI  - HLA-DQA1 allele typing by nonisotopic PCR-LIS-SSCP.
AB  - In the present study we used a simple and reliable method for HLA-DQA1 allele
      typing based on the single-stranded conformation polymorphism (SSCP) properties
      of DNA molecules obtained by PCR. The technique consists of PCR amplification of
      a DNA fragment comprising the second exon of the HLA-DQA1 gene, amplicon
      denaturation using a low ionic strength solution (LIS), and electrophoresis on a
      small native polyacrylamide gel, followed by a rapid silver staining procedure.
      In order to validate the technique and to obtain the allele patterns for the DQA1
      gene, 50 cervical samples were typed using this methodology and the commercial
      Amplitype HLA DQA1 Amplification and Typing kit. All the alleles detected with
      the kit were characterized by the LIS-SSCP approach. This procedure proved to be
      useful for population screening and typing of the DQA1 gene as well as for
      detecting new alleles or mutations in the donor-recipient molecular matching of
      HLA class II genes.

PMID- 11449305
TI  - Heart rate variability under resting conditions in postmenopausal and young
      women.
AB  - The aim of the present study was to compare the modulation of heart rate in a
      group of postmenopausal women to that of a group of young women under resting
      conditions on the basis of R-R interval variability. Ten healthy postmenopausal
      women (mean +/- SD, 58.3 +/- 6.8 years) and 10 healthy young women (mean +/- SD,
      21.6 +/- 0.82 years) were submitted to a control resting electrocardiogram (ECG)
      in the supine and sitting positions over a period of 6 min. The ECG was obtained
      from a one-channel heart monitor at the CM5 lead and processed and stored using
      an analog to digital converter connected to a microcomputer. R-R intervals were
      calculated on a beat-to-beat basis from the ECG recording in real time using a
      signal-processing software. Heart rate variability (HRV) was expressed as
      standard deviation (RMSM) and mean square root (RMSSD). In the supine position,
      the postmenopausal group showed significantly lower (P<0.05) median values of
      RMSM (34.9) and RMSSD (22.32) than the young group (RMSM: 62.11 and RMSSD: 49.1).
      The same occurred in the sitting position (RMSM: 33.0 and RMSSD: 18.9 compared to
      RMSM: 57.6 and RMSSD: 42.8 for the young group). These results indicate a
      decrease in parasympathetic modulation in postmenopausal women compared to young
      women which was possibly due both to the influence of age and hormonal factors.
      Thus, time domain HRV proved to be a noninvasive and sensitive method for the
      identification of changes in autonomic modulation of the sinus node in
      postmenopausal women.

PMID- 11449306
TI  - HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil.
AB  - The aims of the present study were to determine the prevalence of human
      herpesvirus type 8 (HHV-8) in HIV-positive Brazilian patients with (HIV+/KS+) and
      without Kaposi's sarcoma (HIV+/KS-) using PCR and immunofluorescence assays, to
      assess its association with KS disease, to evaluate the performance of these
      tests in detecting HHV-8 infection, and to investigate the association between
      anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples
      from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in
      peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and
      lytic infection by immunofluorescence assay. Positive samples for latent nuclear
      HHV-8 antigen (LNA) antibodies were titrated out from 1/100 to (1/4)09,600
      dilution. Clinical information was collected from medical records and risk
      behavior was assessed through an interview. HHV-8 DNA sequences were detected by
      PCR in 74.3% of KS+ patients and in 3.7% of KS- patients. Serological assays were
      similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+
      patients (79.5%) and KS- patients (18.5%). HHV-8 was associated with KS whatever
      the method used, i.e., PCR (odds ratio (OR) = 7.4, 95% confidence interval (CI) =
      2.16-25.61) or anti-LNA and anti-lytic antibodies (OR = 17.0, 95%CI = 4.91
      59.14). Among KS+ patients, HHV-8 titration levels correlated positively with CD4
      counts (rho 0.48, P = 0.02), but not with KS staging. HHV-8 is involved in the
      development of KS in different geographic areas worldwide, as it is in Brazil,
      where HHV-8 is more frequent among HIV+ patients. KS severity was associated with
      immunodeficiency, but no correlation was found between HHV-8 antibody titers and
      KS staging.

PMID- 11449307
TI  - Expression of c-erbB-2, p53 and c-myc proteins in male breast carcinoma:
      Comparison with traditional prognostic factors and survival.
AB  - There are few data evaluating biological markers for men with breast cancer. The
      purpose of the present study was to analyze the expression of the oncogenes c
      erbB-2 and c-myc and of the suppressor gene p53 by immunohistochemical techniques
      in archival paraffin-embedded tissue blocks of 48 male breast cancer patients,
      treated at the A.C. Camargo Cancer Hospital, Sao Paulo, SP, Brazil. The results
      were compared with clinicopathological prognostic features. Immunopositivity of c
      erbB-2, p53 and c-myc was detected in 62.5, 16.7 and 20.8% of the cases analyzed,
      respectively. Estrogen and progesterone receptors were positive in 75 and 69% of
      the cases, respectively. Increasing staging was statistically associated with c
      erbB-2 (P = 0.04) and weakly related to p53 positivity (P = 0.06). No significant
      correlation between specific survival rate (determined by the log rank test) and
      the molecular markers analyzed was found, whereas the number of compromised lymph
      nodes and advanced TNM (tumor, node, metastasis) staging were associated with
      diminished survival.

PMID- 11449308
TI  - Identification of hemolytic and neuroactive fractions in the venom of the sea
      anemone Bunodosoma cangicum.
AB  - Sea anemones are a rich source of biologically active substances. In crayfish
      muscle fibers, Bunodosoma cangicum whole venom selectively blocks the I K(Ca)
      currents. In the present study, we report for the first time powerful hemolytic
      and neuroactive effects present in two different fractions obtained by gel
      filtration chromatography from whole venom of B. cangicum. A cytolytic fraction
      (Bcg-2) with components of molecular mass ranging from 8 to 18 kDa elicited
      hemolysis of mouse erythrocytes with an EC50 = 14 microg/ml and a maximum dose of
      22 microg/ml. The effects of the neuroactive fraction, Bcg-3 (2 to 5 kDa), were
      studied on isolated crab nerves. This fraction prolonged the compound action
      potentials by increasing their duration and rise time in a dose-dependent manner.
      This effect was evident after the washout of the preparation, suggesting the
      existence of a reversible substance that was initially masking the effects of an
      irreversible one. In order to elucidate the target of Bcg-3 action, the fraction
      was applied to a tetraethylammonium-pretreated preparation. An additional
      increase in action potential duration was observed, suggesting a blockade of a
      different population of K+ channels or of tetraethylammonium-insensitive
      channels. Also, tetrodotoxin could not block the action potentials in a Bcg-3
      pretreated preparation, suggesting a possible interaction of Bcg-3 with Na+
      channels. The present data suggest that B. cangicum venom contains at least two
      bioactive fractions whose activity on cell membranes seems to differ from the I
      K(Ca) blockade described previously.

PMID- 11449309
TI  - Head-to-head comparison of dipyridamole, dobutamine and pacing stress
      echocardiography for the detection of myocardial ischemia in an animal model of
      coronary artery stenosis.
AB  - To compare the sensitivity of dipyridamole, dobutamine and pacing stress
      echocardiography for the detection of myocardial ischemia we produced a
      physiologically significant stenosis in the left circumflex artery of 14 open
      chest dogs (range: 50 to 89% reduction in luminal diameter). In each study,
      dobutamine (5 to 40 microg kg(-1) min(-1) in 3-min stages) and pacing (20 bpm
      increments, each 2 min, up to 260 bpm) were performed randomly, and then followed
      by dipyridamole (up to 0.84 mg/kg over 10 min). The positivity of stress
      echocardiography tests was quantitatively determined by a significant (P<0.05)
      reduction of or failure to increase absolute and percent systolic wall thickening
      in the stenotic artery supplied wall, as compared to the opposite wall (areas
      related to the left anterior descending artery). Systolic and diastolic frozen
      images were analyzed off-line by two blinded observers in the control and stress
      conditions. The results showed that 1) the sensitivity of dobutamine,
      dipyridamole and pacing stress tests was 57, 57 and 36%, respectively; 2) in
      animals with positive tests, the mean percent change of wall thickening in left
      ventricular ischemic segments was larger in the pacing (-19 +/- 11%) and
      dipyridamole (-18 +/- 16%) tests as compared to dobutamine (-9 +/- 6%) (P =
      0.05), but a similar mean reduction of wall thickening was observed when this
      variable was normalized to a control left ventricular segment (area related to
      the left anterior descending artery) (pacing: -16 +/- 7%; dipyridamole: -25 +/-
      16%; dobutamine: -26 +/- 10%; not significant), and 3) a significant correlation
      was observed between magnitude of coronary stenosis and left ventricular
      segmental dysfunction induced by ischemia in dogs submitted to positive stress
      tests. We conclude that the dobutamine and dipyridamole stress tests showed
      identical sensitivities for the detection of myocardial ischemia in this one
      vessel disease animal model with a wide range of left circumflex artery stenosis.
      The pacing stress test was less sensitive, but the difference was not
      statistically significant. The magnitude of segmental left ventricular
      dysfunction induced by ischemia was similar in all stress tests evaluated.

PMID- 11449310
TI  - Role of Tamm-Horsfall protein in the binding and in vivo phagocytosis of type 1
      fimbriated Escherichia coli by mouse peritoneal macrophages.
AB  - Tamm-Horsfall glycoprotein (THP) contains manno-oligosaccharides that are
      recognized by type 1 fimbriae (F1) of Escherichia coli. In the present study, we
      examined the in vivo phagocytic activity of mouse peritoneal macrophages after
      treatment of bacteria with THP. At low THP concentrations (12.5 microg/ml and 50
      microg/ml) no significant difference was observed in the phagocytosis of E. coli
      F1+. However, at high THP concentrations (500 microg/ml and 1250 microg/ml) we
      obtained a reduction of bacterial phagocytosis by mouse peritoneal macrophages.

PMID- 11449311
TI  - Behavioral correlates of the activity of serotonergic and non-serotonergic
      neurons in caudal raphe nuclei.
AB  - We investigated the behavioral correlates of the activity of serotonergic and non
      serotonergic neurons in the nucleus raphe pallidus (NRP) and nucleus raphe
      obscurus (NRO) of unanesthetized and unrestrained cats. The animals were
      implanted with electrodes for recording single unit activity, parietal
      oscillographic activity, and splenius, digastric and masseter electromyographic
      activities. They were tested along the waking-sleep cycle, during sensory
      stimulation and during drinking behavior. The discharge of the serotonergic
      neurons decreased progressively from quiet waking to slow wave sleep and to fast
      wave sleep. Ten different patterns of relative discharge across the three states
      were observed for the non-serotonergic neurons. Several non-serotonergic neurons
      showed cyclic discharge fluctuations related to respiration during one, two or
      all three states. While serotonergic neurons were usually unresponsive to the
      sensory stimuli used, many non-serotonergic neurons responded to these stimuli.
      Several non-serotonergic neurons showed a phasic relationship with splenius
      muscle activity during auditory stimulation. One serotonergic neuron showed a
      tonic relationship with digastric muscle activity during drinking behavior. A few
      non-serotonergic neurons exhibited a tonic relationship with digastric and/or
      masseter muscle activity during this behavior. Many non-serotonergic neurons
      exhibited a phasic relationship with these muscle activities, also during this
      behavior. These results suggest that the serotonergic neurons in the NRP and NRO
      constitute a relatively homogeneous population from a functional point of view,
      while the non-serotonergic neurons form groups with considerable functional
      specificity. The data support the idea that the NRP and NRO are implicated in the
      control of somatic motor output.

PMID- 11449312
TI  - Reliability and validity of the interactive observation scale for psychiatric
      inpatients applied by nursing aides in daily ward practice.
AB  - The main characteristic of the nursing Interactive Observation Scale for
      Psychiatric Inpatients (IOSPI) is the necessity of interaction between raters and
      patients during assessment. The aim of this study was to evaluate the reliability
      and validity of the scale in the "real" world of daily ward practice and to
      determine whether the IOSPI can increase the interaction time between raters and
      patients and influence the raters' opinion about mental illness. All inpatients
      of a general university hospital psychiatric ward were assessed daily over a
      period of two months by 9 nursing aides during the morning and afternoon shifts,
      with 273 pairs of daily observations. Once a week the patients were interviewed
      by a psychiatrist who filled in the Brief Psychiatric Rating Scale (BPRS). The
      IOSPI total score was found to show significant test-retest reliability
      (interclass correlation coefficient = 0.83) and significant correlation with the
      BPRS total score (r = 0.69), meeting the criteria of concurrent validity. The
      instrument can also discriminate between patients in need of further inpatient
      treatment from those about to be discharged (negative predictive value for
      discharge = 0.91). Using this scale, the interaction time between nursing aides
      and patients increased significantly (t = 2.93, P<0.05) and their opinion about
      the mental illness changed. The "social restrictiveness" factor of the opinion
      scale about mental illness showed a significant reduction (t = 4.27, P<0.01) and
      the "interpersonal etiology" factor tended to increase (t = 1.98, P = 0.08). The
      IOSPI was confirmed as a reliable and valid scale and as an efficient tool to
      stimulate the therapeutic attitudes of the nursing staff.

PMID- 11449313
TI  - Sex hormone modulation of serotonin-induced coronary vasodilation in isolated
      heart.
AB  - The present study was designed to evaluate the differences in the coronary
      vasodilator actions of serotonin (5-HT) in isolated heart obtained from naive or
      castrated male and female rats that were treated with either estrogen or
      testosterone. Hearts from 12 groups of rats were used: male and female naive
      animals, castrated, castrated and treated with 17beta-estradiol (0.5 microg kg(
      1) day(-1)) for 7 or 30 days, and castrated and treated with testosterone (0.5 mg
      kg(-1) day(-1)) for 7 or 30 days. After treatment, the vascular reactivity of the
      coronary bed was evaluated. Baseline coronary perfusion pressure (CPP) was
      determined and dose-response curves to 5-HT were generated. Baseline CPP differed
      between male (70 +/- 6 mmHg, N = 10) and female (115 +/- 6 mmHg, N = 12) naive
      rats. Maximal 5-HT-induced coronary vasodilation was higher (P<0.05) in naive
      female than in naive male rats. In both sexes, 5-HT produced endothelium
      dependent coronary vasodilation. After castration, there was no significant
      difference in baseline CPP between hearts obtained from male and female rats (75
      +/- 7 mmHg, N = 8, and 83 +/- 5 mmHg, N = 8, respectively). Castration reduced
      the 5-HT-induced maximal vasodilation in female and male rats (P<0.05). Estrogen
      treatment of castrated female rats restored (P<0.05) the vascular reactivity. In
      castrated male rats, 30 days of estrogen treatment increased (P<0.05) the
      responsiveness to 5-HT. The endothelium-dependent coronary vasodilator actions of
      5-HT are greater in female rats and are modulated by estrogen. A knowledge of the
      mechanism of action of estrogen on coronary arteries could aid in the development
      of new therapeutic strategies and potentially decrease the incidence of
      cardiovascular disease in both sexes.

PMID- 11449314
TI  - Heart rate and body weight alterations in juvenile specimens of the tropical land
      snail Megalobulimus sanctipauli during dormancy.
AB  - The time course of heart rate and body weight alterations during the natural
      period of dormancy were determined in active feeding and dormant juvenile
      specimens of Megalobulimus sanctipauli. In both groups, heart rate markedly
      decreased during the first 40 days of dormancy, tending to stabilize thereafter.
      This time period coincided with the decrease in environmental temperature during
      autumn-winter. At the end of the dormancy period, surviving active feeding and
      dormant snails showed a significant decrease in heart rate which, however, was
      significantly greater in the latter group. Total body weight decreased
      concomitantly with heart rate in dormant snails but remained constant in active
      feeding snails. Body hydration induced significant increases in weight and heart
      rate in surviving dormant snails. Feeding following hydration promoted a new
      significant increase in heart rate but not in weight. These results indicate that
      the decrease in heart rate observed in juvenile specimens of M. sanctipauli
      during dormancy may be due to at least three factors: 1) decrease in
      environmental temperature during autumn-winter, 2) starvation which leads to the
      depletion of endogenous fuel reserves and to a probable decrease in hemolymph
      nutrient levels, and 3) dehydration which leads to a probable decrease in
      hemolymph volume and venous return and/or to an increase in hemolymph osmolarity.

PMID- 11449315
TI  - Association of retinopathy with a microsatellite at 5' end of the aldose
      reductase gene in Chinese patients with late-onset Type 2 diabetes.
AB  - Recent experimental data suggest that a microsatellite polymorphism at 5' end of
      the aldose reductase gene may be associated with the development of diabetic
      retinopathy. In the present study, we examined the allele distribution of the
      polymorphism in 384 Hong Kong Chinese patients who had late-onset (age at
      diagnosis > or =35 years) Type 2 diabetes, but no clinical evidence of cataract.
      Approximately 17% of them (n = 64) had retinopathy. The patients with retinopathy
      were older (52 +/- 11 years vs. 60 +/- 9 years, p < 0.01) and had a higher HbA1c
      (8.9 +/- 2.2% vs. 7.7 +/- 2.0%, p < 0.01 with adjustment for age) than those
      without the complication. Amongst all of the patients, we detected 10
      microsatellite alleles and found that allele Z-4 was overpresented in those with
      retinopathy (9% vs. 4%, p < 0.05). There were no significant differences in
      allelic distributions of the major alleles Z + 2, Z, and Z-2, which accounted for
      more than 80% of the overall frequency, between the two groups of patients. Using
      multiple logistic regression analysis (R2 = 0.17, p < 0.01), we found that age (p
      < 0.01) and HbA1c (p < 0.05) were associated with retinopathy. In conclusion, our
      data suggest that the occurrence of diabetic retinopathy in the Chinese
      population may be influenced by clinical and metabolic factors. The aldose
      reductase gene may be implicated, but is not likely to play a major role.

PMID- 11449316
TI  - Further refinement of the MYP2 locus for autosomal dominant high myopia by
      linkage disequilibrium analysis.
AB  - INTRODUCTION: High myopia (>-6.00 diopters) is a complex common disorder that
      predisposes individuals to retinal detachment, glaucoma, macular degeneration,
      and premature cataracts. A recent linkage analysis of seven families with
      autosomal dominant high myopia has identified one locus (MYP2) for high myopia on
      chromosome 18p11.31 (Young et al.: Am J Hum Genet 1998;63:109-119). Haplotype
      analysis revealed an initial interval of 7.6 centimorgans (cM). METHODS:
      Transmission disequilibrium tests (TDT) with both the Statistical Analysis for
      Genetic Epidemiology (SAGE) 3.1 TDTEX and GENEHUNTER 2 (GH2) programs were
      performed using chromosome 18p marker alleles for this interval. RESULTS: Using
      SAGE analysis, the following p values were obtained for markers in marker order
      in this region: D18S1146 (p = 0.227), D18S481 (p = 0.001), D18S63 (p = 0.062),
      D18S1138 (p = 0.0004), D18S52 (p = 1.79 x 10(-6)), and D18S62 (p = 0.141). GH2
      TDT analysis revealed the following p values for the best allele for the markers:
      D18S1146 (p = 0.083), D18S481 (p = 0.108), D18S63 (p = 0.034), D18S1138 (p =
      0.011), D18S52 (p = 0.007), and D18S62 (p = 0.479). CONCLUSION: These data
      suggest that the gene for 18p11.31-linked high myopia is most proximal to marker
      D18S52, with a likely interval of 0.8 cM between markers D18S63 and D18S52. Due
      to the contraction of the interval size by TDT, these results provide a basis for
      focused positional cloning and candidate gene analysis at the MYP2 locus.

PMID- 11449317
TI  - Osteosarcoma following retinoblastoma: age at onset and latency period.
AB  - In order to assess the role of genetic predisposition in the induction of
      radiation-induced tumors, we performed statistical analysis on data from the
      literature and from our own Institute with regard to the age at onset and the
      latency period of osteosarcoma as the second primary tumor for retinoblastoma
      with or without subsequent radiotherapy. In retinoblastoma survivors who
      subsequently developed osteosarcoma, the age at onset of retinoblastoma was young
      (average of 12 months) in both unilateral and bilateral forms. This suggests that
      all or almost all of the patients were genetically predisposed by a mutation of
      one allele of the RB1 gene. For retinoblastoma patients, osteosarcomas occurred
      1.2 years earlier inside than outside the radiation field. The latency period
      between radiotherapy and osteosarcoma onset was 1.3 years shorter inside than
      outside the radiation field. Interestingly, a bimodal distribution of latency
      periods was observed for osteosarcomas arising inside, but not outside the
      radiation field: 40% occurred after a short latency, while the latency of the
      remaining 60% was comparable to that of osteosarcoma occurring outside the
      radiation field. This suggests that different mechanisms may be involved in
      radiocarcinogenesis. A radiation-induced mutation of the second RB1 allele may be
      the cause of osteosarcomas occurring after a short delay, while other genes may
      be affected in those occurring after a longer delay.

PMID- 11449318
TI  - Screening for CRX gene mutations in Chinese patients with Leber congenital
      amaurosis and mutational phenotype.
AB  - PURPOSE: To screen for possible disease-causing mutations in the CRX gene in
      Chinese patients with Leber congenital amaurosis (LCA) and to enrich the
      understanding of its mutational phenotype. METHODS: Genomic DNA was collected
      from 27 patients with LCA. The coding sequences of the CRX gene were analyzed
      using the PCR-heteroduplex-SSCP method. Mutations were confirmed by DNA
      sequencing. RESULTS: We identified two heterozygous variations in the CRX gene in
      two patients with LCA. One was a deletion (GCC-->-CC, A181D1bp) leading to a
      frameshift and protein truncation. This mutation was present in a patient with
      LCA, but not in his healthy parents. The ocular manifestations of this
      A181Delta1bp mutation are described. An intronic variation (IVS1-13G-->C) was
      found in a patient with LCA as well as in his healthy father. CONCLUSION: A
      heterozygous A181D1bp mutation in the CRX gene caused an LCA phenotype in a
      Chinese patient.

PMID- 11449319
TI  - Electrophysiological findings in two young patients with Bothnia dystrophy and a
      mutation in the RLBP1 gene.
AB  - PURPOSE: To characterize the clinical phenotype, with emphasis on
      electrophysiology, of two children with suspected Bothnia dystrophy. METHODS: Two
      unrelated affected patients, 10 and 11 years old, were studied. Ophthalmological
      examination included testing of visual acuity, fundus inspection and fundus
      photography, kinetic perimetry, full-field electroretinogram (ERG), and
      multifocal ERG. The presence of a mutation in exon 7 of the RLBP1 gene was
      investigated by DNA sequencing. RESULTS: Both patients were homozygous for the
      Arg234Trp-causing mutation in the RLBP1 gene, but the resulting disease phenotype
      appeared to vary somewhat between them. Visual acuity was moderately reduced in
      one patient and normal in the other. Fundus inspection at this age revealed no
      pathology in either patient and there were no signs of retinitis punctata
      albescens, which has been described previously as a frequent clinical feature of
      Bothnia dystrophy. The result of kinetic perimetry was normal. The final rod
      threshold was moderately elevated. Full-field ERG demonstrated the uncommon
      combination of absent rod response and normal cone response after 40 minutes of
      dark adaptation. However, after prolonged dark adaptation (20-24 h), both the rod
      response and the dark adaptation threshold became normal. Multifocal ERG was
      performed in one of the patients (the one with normal visual acuity and normal
      fundus appearance) and showed a reduced cone response in the central region of
      the tested area. There was no improvement of the multifocal ERG result after 20
      24 h of dark adaptation. CONCLUSION: Patients with mutations in the RLBP1 gene
      (Arg234Trp) may have a normal fundus appearance early in the disease course.
      Multifocal ERG can be used for the objective documentation of the disturbed
      macular function, especially when the patient's visual acuity and fundus
      appearance are normal. The rod response is absent in the electroretinogram;
      however, after prolonged dark adaptation (20-24 hours), the rods recover
      completely. The central cones do not seem to recover.

PMID- 11449320
TI  - Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the
      VMD2 gene.
AB  - PURPOSE: To describe the clinical phenotype in a family with Best's vitelliform
      macular dystrophy (BMD) and a new mutation (Val89Ala) in the VMD2 gene. METHODS:
      The genotype was determined by direct sequence analysis of the individual exons
      of VMD2. Nine members of a family with BMD were examined. The examination
      included best-corrected visual acuity, electro-oculography (EOG), fundus
      examination, and photography. Four of the patients were also examined with full
      field ERG and three with multifocal ERG. RESULTS: A T-to-C substitution was
      identified at position 370 in the cDNA of VMD2, leading to a Val89Ala change in
      the protein. Six patients, five with the Val89Ala mutation and a nine-year-old
      boy without the mutation, presented with a pathological Arden ratio on EOG
      examination. Most of the patients with BMD in this family had an onset of visual
      failure by the age of 40-50 years. The older patients in the family demonstrated
      atrophic macular dystrophy. CONCLUSIONS: Patients with BMD and the Val89Ala
      mutation in the VMD2 gene can present with a phenotype of a mostly late-onset
      visual failure. These BMD patients, who present with visual failure and macular
      degeneration in middle age, can be misdiagnosed as being affected with adult
      onset macular dystrophies instead of BMD, because the latter is often regarded as
      a disease of childhood and adolescence.

PMID- 11449321
TI  - An infant with Down syndrome and retinoblastoma. A possible non-fortuitous
      association.
AB  - AIM: To evaluate the association between Down syndrome and retinoblastoma.
      METHOD: Presentation of a case report and review of the literature. RESULTS: A
      retinoblastoma was observed in a 10-month-old boy with Down syndrome. A review of
      the literature yielded 14 other cases, suggesting a possible excess of
      retinoblastoma in Down syndrome, as previously proposed by two epidemiological
      studies. The possible roles of external physical agents and hyperplastic and
      dysplastic lesions of the retina in subjects with Down syndrome is discussed.
      CONCLUSION: A positive association between Down syndrome and retinoblastoma is
      possible. An epidemiological study on this subject is needed to better ascertain
      this potential link.

PMID- 11449322
TI  - Frontiers of polymerase chain reaction diagnostics for uveitis.
AB  - The polymerase chain reaction (PCR) is a powerful molecular biologic technique
      for the detection of pathogen DNA. Recent technical advances in the technique
      have broadened its scope considerably. Emerging applications of PCR in pathogen
      strain typing, rapid screening of differential diagnoses, and pathogen discovery
      are discussed.

PMID- 11449323
TI  - Immune response to retinal antigens in patients with gyrate atrophy and other
      hereditary retinal dystrophies.
AB  - PURPOSE: Gyrate atrophy (GA) is a rare hereditary disease that causes retinal
      destruction. Retinal damage in GA and other heredodegenerative diseases such as
      retinitis pigmentosa (RP) releases sequestered antigens and may trigger immune
      response to these molecules. Here, we studied the immune response to retinal
      antigens in patients with GA and RP and compared it with that of patients with
      inactive posterior uveitis and normal volunteers. PATIENTS AND METHODS:
      Peripheral blood was collected from 24 patients with RP, 10 patients with GA, 10
      patients with inactive posterior uveitis, and 16 normal volunteers. Cell-mediated
      immune responses to human S-antigen (HS-Ag), bovine S-antigen (BS-Ag), and
      interphotoreceptor retinoid-binding protein (IRBP) were investigated by
      lymphocyte proliferation assay. In addition, serum levels of soluble
      intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion
      molecule-1 (sVCAM-1) were studied by ELISA. Immunologic data were correlated with
      clinical and electrophysiological findings. RESULTS: Patients with GA or RP
      responded to HS-Ag and BS-Ag more vigorously than patients with uveitis or
      healthy controls, as shown by higher mean stimulation indices and larger
      proportions of responders. Unlike S-Ag, IRBP stimulated low lymphocyte responses
      in only a small proportion of RP patients. The mean sVCAM-1 levels were
      significantly higher in the sera from patients with GA than in that from normal
      controls. CONCLUSION: An elevated cellular immune response to S-Ag is common in
      patients with GA and RP. This elevated cellular immune response to S-Ag may
      exacerbate retinal destruction in patients with GA and RP.

PMID- 11449324
TI  - Circulating antibodies to inducible heat shock protein 70 in patients with
      uveitis.
AB  - Heat shock proteins with molecular weight 70 kDa (hsp70) are highly conserved
      immunogenic intracellular molecules. There are two main subtypes: one is
      expressed constitutively (hsc70), while the other is induced under stressful
      conditions (ihsp70). Using an ELISA directed against recombinant human ihsp70,
      antibody titers were determined in patients with defined ocular inflammatory
      conditions (Behcet's disease, Vogt-Koyanagi-Harada (VKH), pars planitis, and
      sarcoidosis) as well as in a group of age-matched normal volunteers. In
      comparison to healthy controls (n = 14, absorbance 0.269), levels were
      significantly elevated in Behcet's disease (n = 18; 0.412), sarcoidosis (n = 15;
      0.432), and pars planitis (n = 13; 0.346), but not in VKH (n = 10; 0.263). A
      correlation was also noted for treatment versus no treatment in pars planitis (p
      = 0.028), but not in other inflammatory conditions. There was no correlation with
      the level of intraocular disease activity as defined by vitreous haze and vision
      drop. Since pars planitis is a purely ocular condition, circulating levels of
      ihsp antibodies likely reflect the extent of disease involvement within the eye.

PMID- 11449325
TI  - Pars planitis: epidemiology, treatment, and association with multiple sclerosis.
AB  - During retrospective and prospective studies, we attempted to determine the
      clinical characteristics, treatment, and visual outcome of patients with pars
      planitis and to evaluate the association between pars planitis and multiple
      sclerosis (MS). The retrospective study included 44 patients with pars planitis,
      who had been examined between October 1986 and January 1999. We analyzed age,
      sex, visual acuity (VA), median follow-up time, and medical and surgical
      treatments. The prospective study, which included 21 consecutive patients with
      pars planitis, was performed to determine the presence of MS. In the
      retrospective study, the mean patient age was 22.4 years (SD +/- 11.5) and the
      median follow-up was 34.9 months (SD +/- 27.2). Complications included macular
      edema (47.7%), vitreous opacities (38.6%), papillitis (38.6%), vasculitis
      (36.4%), and cataract (20.5%). Forty patients (90.9%) had a final bilateral VA
      better than 20/40. In the prospective study, magnetic resonance imaging (MRI) was
      performed. Demyelinating lesions were found in 10 (47.6%) of the 21 patients and
      relapsing-remitting clinically definite MS was diagnosed in seven (33.3%). With
      the exception of age, no significantly statistical differences were observed when
      the visual prognosis and the clinical and epidemiologic characteristics were
      compared between the two groups of patients with and without associated MS; a
      diagnosis of MS was more frequently made in patients over 25 years of age. With
      appropriate treatment, patients with pars planitis have a good visual prognosis.
      Because the presence of demyelinating lesions seems to be high among patients
      with pars planitis, MRI should be considered, especially in patients over 25
      years of age.

PMID- 11449326
TI  - Herpes simplex virus type 2: a cause of acute retinal necrosis syndrome.
AB  - PURPOSE: To describe a case of herpes simplex virus type 2 (HSV-2) acute retinal
      necrosis syndrome (ARN) in a 13-year-old immunocompetent girl. METHODS:
      Polymerase chain reaction (PCR), cultures, flow cytometry, and cytology were
      performed on the vitreous sample. RESULTS: Both PCR studies and vitreous cultures
      revealed HSV-2 as the cause of ARN. Flow cytometry showed CD4+, CD8+, and natural
      killer cells. The visual outcome of the patient was 20/200. CONCLUSION:
      Successful culture of HSV-2 from the vitreous specimen in a patient with ARN
      proved HSV-2 to be one of the causes of ARN. The successful culture of HSV-2 has
      not been previously reported.

PMID- 11449327
TI  - Clinical course of ocular Behcet's disease in siblings.
AB  - PURPOSE: Familial occurrence has been reported in approximately 8% of Turkish
      patients with Behcet's disease. Our aim was to compare the clinical course of
      ocular Behcet's disease among siblings. METHODS: We retrospectively studied five
      pairs of siblings with ocular involvement of Behcet's disease. No other family
      member of these siblings had any symptom of Behcet's disease. RESULTS: The
      siblings comprised three sister-brother pairs, one sister-sister pair, and one
      brother-brother pair. There was a 5-10-year difference between the age at onset
      of ocular disease among siblings. Three of the five pairs (two sister-brother,
      one brother-brother) had a dissimilar course of disease activity. Female siblings
      had an earlier age at onset and tended to have a worse prognosis than their
      brothers. CONCLUSIONS: It is generally acknowledged that male sex is associated
      with a worse prognosis. In this study, however, we observed that, among siblings
      with a dissimilar course, female patients were more severely affected than male
      patients. Poor ocular prognosis in a patient does not indicate aggressive
      treatment in his/her sibling. We believe that each sibling should be managed on
      an individual basis.

PMID- 11449328
TI  - Central retinal vein occlusion due to herpes zoster as the initial presenting
      sign in a patient with acquired immunodeficiency syndrome (AIDS).
AB  - Central retinal vein occlusion (CRVO) due to herpes zoster has rarely been
      reported. Varicella zoster virus is a common opportunistic infection in patients
      with AIDS. This case report is about a 40-year-old man with herpes zoster
      ophthalmicus and central retinal vein occlusion of the right eye who is HIV
      positive. Although the lesion resolved following treatment with intravenous
      acyclovir and oral steroid, the patient subsequently developed florid disc
      neovascularization and vitreous hemorrhage. The paper highlights CRVO as the
      initial presentation in an AIDS patient with herpes zoster ophthalmicus.

PMID- 11449329
TI  - The concern of viral safety in the treatment of hemophilia.

PMID- 11449330
TI  - Structural and functional characterization of B-domain deleted recombinant factor
      VIII.
AB  - A new high-purity recombinant factor VIII preparation has been developed for the
      treatment of hemophilia A. Structurally, this factor VIII preparation, B-domain
      deleted recombinant factor VIII (BDDrFVIII), differs from other recombinant and
      plasma-derived factor VIII preparations in that most of the B-domain has been
      deleted. To ensure that BDDrFVIII contains the requisite structural and
      functional features, it has been subjected to detailed biochemical and
      biophysical characterization in comparison to the plasma-derived form of factor
      VIII. Laboratory studies have shown that the primary, secondary, and tertiary
      structures of BDDrFVIII and the posttranslational modifications are similar to
      those of the [80 + 90]-kd form of plasma-derived factor VIII. In addition,
      BDDrFVIII has full biologic activity compared with full-length factor VIII
      preparations.

PMID- 11449331
TI  - Measurement of factor VIII activity of B-domain deleted recombinant factor VIII.
AB  - The factor VIII activity of B-domain deleted recombinant factor VIII (BDDrFVIII)
      measured by activated partial thromboplastin time (APTT)-based one-stage assays
      is approximately 50% of the activity obtained by the chromogenic assay. Similar
      results have been reported for the two licensed full-length recombinant factor
      VIII products. In view of these findings, comprehensive studies have been
      undertaken to find the cause of the assay differences. Only the phospholipid
      reagent, used as a platelet substitute in the one-stage assay, proved to be
      crucial for explaining the assay difference. When platelet-rich plasma was used
      as the source of phospholipid in the one-stage assay, the factor VIII activity
      assay results correlated well with those measured by the chromogenic assay.
      Similar results were obtained when the platelets were replaced by liposomes
      prepared using platelet factor 3 (PF3) as a model that has a low content (5% to
      10%) of phosphatidylserine (PS). In contrast, the use of liposomes with 20% to
      30% PS, as in the crude lipid extracts used in ordinary APTT reagents, resulted
      in underestimation of the factor VIII activity. Antigen measurements using an
      enzyme-linked immunosorbent assay (ELISA) method demonstrated a good correlation
      between the antigen and chromogenic activity, but not always between antigen and
      one-stage activity results. Based on these findings and the clinical data, it can
      be concluded that the chromogenic assay most accurately measures the functional
      activity of BDDrFVIII. However, modifications of the one-stage assay, such as the
      use of a product-specific standard or development of a PF3-like phospholipid
      reagent, could address the observed assay discrepancies.

PMID- 11449332
TI  - The manufacturing process for B-domain deleted recombinant factor VIII.
AB  - The development of a cell bank used in the routine manufacturing of a B-domain
      deleted recombinant coagulation factor VIII (BDDrFVIII) molecule involved stable
      insertion of the human BDDrFVIII gene into Chinese hamster ovary (CHO) cells,
      selection of a cell line capable of expressing consistent levels of active
      BDDrFVIII, and the establishment of a cell bank. The manufacturing process begins
      with the culturing of CHO cells in large bioreactors. Product synthesis is
      initiated by altering the cell culture conditions, thereby arresting the cells in
      a stationary growth phase and inducing elevated expression of BDDrFVIII.
      Harvested culture medium is concentrated by chromatography and then purified
      through a series of four column chromatography steps and one solvent-detergent
      virus inactivation step. By eliminating the presence of human serum albumin in
      the final formulation, the BDDrFVIII-containing coagulant product meets with a
      high standard of safety against microbial and viral contamination. Extensive
      studies have shown that BDDrFVIII is a consistent, highly pure factor VIII for
      the treatment of patients with hemophilia A.

PMID- 11449333
TI  - Viral safety of B-domain deleted recombinant factor VIII.
AB  - The possible transmission of blood-borne pathogens has been the impetus behind
      the development of recombinant products formulated in the absence of human
      derived components. The viral safety of Chinese hamster ovary (CHO)-cell-based
      pharmaceuticals is well established. Over 100 million infusions have been
      administered without a single known incident of CHO-related viral transmission.
      The manufacturing process for B-domain deleted recombinant factor VIII
      (BDDrFVIII) builds on this safety record by using a state-of-the-art multitiered
      approach to viral safety. This approach includes: (1) extensive testing of the
      CHO cells used to produce BDDrFVIII; (2) routine viral monitoring of the cell
      culture production process; (3) a purification process in which a specific viral
      inactivation procedure has been included; (4) a final formulation that does not
      incorporate human albumin as the stabilizer; and (5) a thorough validation of the
      viral inactivation and removal capacity of the purification process. This
      multifaceted viral safety program offers the hemophilia community a factor VIII
      product with an exceptional degree of viral safety.

PMID- 11449334
TI  - B-domain deleted recombinant factor VIII formulation and stability.
AB  - B-domain deleted recombinant factor VIII (BDDrFVIII) is a deletion form of human
      coagulation factor VIII. A lyophilized formulation of highly purified BDDrFVIII
      has been developed that does not require the use of blood-derived products such
      as human serum albumin (HSA). By avoiding the use of blood-derived products, the
      BDDrFVIII formulation minimizes the risk of transmitting blood-borne pathogens
      that may be present in plasma-derived factor VIII or in other recombinant factor
      VIII products that contain HSA in their formulation. Upon reconstitution with
      saline (4 mL), the composition of the reconstituted product (62.5 to 250 IU/mL
      BDDrFVIII) is 18 mg/mL sodium chloride, 3.0 mg/mL sucrose, 1.5 mg/mL L-histidine,
      0.25 mg/mL calcium chloride dihydrate, and 0.1 mg/mL polysorbate 80. The optimal
      combination of these excipients in the lyophilized BDDrFVIII formulation provides
      long-term stability, as measured by a variety of analytical methods. The
      formulation preserves factor VIII activity of lyophilized BDDrFVIII during
      storage for at least 24 months at 8 degrees C, and for up to 6 months at room
      temperature (25 degrees C). The reconstituted product retains its factor VIII
      potency for at least 100 hours at 25 degrees C, which would allow it to be
      continuously administered via an infusion pump, assuming the product is handled
      under aseptic conditions.

PMID- 11449335
TI  - Clinical evaluation of B-domain deleted recombinant factor VIII in previously
      treated patients.
AB  - The pharmacokinetics, safety, and efficacy of B-domain deleted recombinant factor
      VIII (BDDrFVIII) were evaluated in patients with hemophilia A. In an initial 12
      month study with subsequent yearly extensions over a 5-year period, 113
      previously treated patients (PTPs) received on-demand and/or prophylactic
      treatment with BDDrFVIII, including treatment during surgery, if required. Half
      life and recovery of factor VIII activity remained unchanged over the study
      period. The mean elimination half-life was 10.5 +/- 2.6 hours at baseline and
      10.4 +/- 3.3 hours at month 12. A total of 7,310 hemorrhages occurred for
      patients who received on-demand treatment, with 71% resolving after a single
      infusion. Of the 11,655 rated infusions given for hemorrhages, 92% were rated by
      investigators and patients as providing an "excellent" or "good" response. These
      results are consistent with efficacy data from other trials using recombinant
      factor VIII products. During the prophylactic period, 12% of patients experienced
      no bleeding episodes, and 17% of the patients had no on-demand treatment. The
      mean dose was 28 IU/kg for prophylactic treatment and 30 IU/kg for on-demand
      treatment. The efficacy of administering BDDrFVIII in conjunction with surgery
      was assessed to be "very useful" or "useful" in all cases. Few adverse events
      were reported, and only one patient developed inhibitors to factor VIII activity.
      The results show that BDDrFVIII provides a safe and effective treatment of
      hemophilia A when given as on-demand therapy, in routine or intermittent
      prophylaxis, or during surgery.

PMID- 11449336
TI  - Clinical evaluation of B-domain deleted recombinant factor VIII in previously
      untreated patients.
AB  - The safety and efficacy of B-domain deleted recombinant factor VIII (BDDrFVIII)
      were evaluated in previously untreated patients (PUPs) with severe hemophilia A.
      In an open-label multicenter study, 101 PUPs received routine prophylactic and/or
      on-demand treatment with BDDrFVIII, including treatment related to surgery for 50
      exposure days for up to 5 years. The pharmacokinetic measurements (ie,
      elimination half-life and in vivo mean recovery) assessed at baseline and 12
      months were stable for BDDrFVIII over time. A total of 1,362 hemorrhages
      occurred. Ninety-two percent (1,258/1,362) of bleeding episodes resolved after
      three infusions or fewer. Of the 2,375 infusions rated by investigators, 93%
      (2,215/2,375) were rated as providing an "excellent" or "good" response. Twenty
      seven patients received routine prophylactic treatment, which significantly
      reduced breakthrough bleeding episodes by twofold when compared with patients who
      were treated on-demand. Administration in conjunction with 40 surgical procedures
      showed no adverse effects, and the overall assessment was either "very useful" or
      "useful." The mean dose was 56 IU/kg for routine primary prophylaxis and 53 IU/kg
      for on-demand therapy for bleeding episodes in patients who were assessed to be
      inhibitor-free at the time of infusion. Thirty-two percent of patients developed
      inhibitors. Of these, 16 patients were high responders (peak titer > or = 5
      Bethesda units [BU]). The inhibitor risk was comparable to that seen with full
      length recombinant products. BDDrFVIII was found to be effective, safe, and well
      tolerated.

PMID- 11449337
TI  - A targeted approach to thrombosis: new data, new perspectives. Proceedings of a
      symposium. August 20, 1999. Washington, DC, USA.

PMID- 11449338
TI  - Developing a novel antithrombotic in the academic environment.
AB  - In recent years, academic research institutions have increasingly sought to
      commercialize their discoveries, providing the opportunity to raise venture
      capital and benefit financially from their developments. In the last 6 years,
      Hamilton Civic Hospitals Research Center, affiliated with McMaster University,
      Ontario, Canada, has set up two companies, Vascular Therapeutics and Osteokine,
      to commercialize its discoveries in thrombosis and osteoporosis. Epidemiological
      evidence shows a continuing socioeconomic burden of both of these disorders,
      thereby offering opportunities for new drug development. Key areas in the field
      of thrombosis include novel parenteral anticoagulants to replace heparin as
      adjunctive therapy in acute coronary syndromes, safer and more practical oral
      anticoagulants that do not require monitoring to replace coumarins, and oral
      antiplatelet drugs for use in combination with aspirin. Since their creation,
      Vascular Therapeutics and Osteokine have attracted major funding and developed
      several patentable compounds that show clinical and commercial promise.

PMID- 11449339
TI  - Effective risk stratification of surgical and nonsurgical patients for venous
      thromboembolic disease.
AB  - Effective and safe methods of preventing venous thromboembolism (VTE) are now
      widely available, but a significant proportion of patients develop VTE either
      because thromboprophylaxis has not been used or because the intensity of
      thromboprophylaxis is not matched to the level of risk. Thromboembolic risk
      varies widely according to the clinical setting and presence of underlying risk
      factors, but VTE may not be suspected even in high-risk patients. Clinical risk
      factors for VTE include recent surgery, cancer, stroke, previous VTE,
      immobilization, and advanced age. Recent attention has focused on the role of
      inherited and acquired molecular factors in determining overall thromboembolic
      risk. These factors include the classic thrombophilias-deficiencies of
      antithrombin III, protein C, and protein S-and several newly described molecular
      risk factors: factor V Leiden, the prothrombin 20210A gene mutation, and
      hyperhomocysteinemia. Based on emerging knowledge of risk factors, several risk
      assessment models (RAMs) have been devised that stratify patients according to
      overall VTE risk, allowing thromboprophylaxis to be tailored appropriately.
      Compared with older risk assessment formulas, current RAMs are simpler and
      include specific recommendations for thromboprophylaxis based on the available
      scientific evidence. Consensus documents on VTE prevention classify patients into
      low-, moderate-, and high-risk categories. More recently, a new risk group, very
      high risk, has been described. Very-high-risk patients are especially prone to
      thromboembolic complications and need intensive and in some cases prolonged
      thromboprophylaxis.

PMID- 11449340
TI  - The potential role of new therapies in deep-vein thrombosis prophylaxis.
AB  - The value of prophylaxis against venous thromboembolism (VTE) is increasingly
      accepted in most surgical specialties, although the potential reduction in fatal
      pulmonary embolism has recently been questioned. The burden of VTE in hospital
      patients nevertheless remains high, partly attributable to underuse of
      thromboprophylaxis and partly attributable to occurrence of VTE in high-risk
      patients because recommended antithrombotic therapies fail to provide full
      protection. Improved physician education has been shown to increase the
      application of antithrombotic measures, and research efforts are focused on
      developing novel antithrombotic agents with greater efficacy and safety in
      clinical use. Several novel indirect and direct thrombin inhibitors have been
      investigated. The heparinoid danaparoid has shown superiority over unfractionated
      heparin in several indications, but only the recombinant hirudin, desirudin, has
      exhibited greater efficacy than low-molecular-weight heparin (LMWH) in
      thromboprophylaxis for patients undergoing elective hip-replacement surgery,
      without increasing the risk of bleeding. Three large-scale clinical trials have
      shown desirudin to be the most effective thromboprophylactic agent currently
      available in elective hip-replacement surgery; this agent has now been licensed
      for use in orthopedic surgery. Research is ongoing into the feasibility of still
      more effective and convenient therapies, such as oral antithrombins.

PMID- 11449341
TI  - Benefits of deep-vein thrombosis prophylaxis in the nonsurgical patient: The
      MEDENOX trial.
AB  - Venous thromboembolism (VTE) is a common complication of hospitalized patients,
      imposing a major clinical and economic burden. Three of four cases of fatal
      pulmonary embolism occur in nonsurgical settings, but thromboprophylaxis is far
      less common in medical than in surgical patients. This is mainly attributable to
      the heterogeneity of nonsurgical populations and lack of high-quality evidence to
      support specific thromboprophylactic measures. The recent Prophylaxis of Venous
      Thromboembolism in MEDical Patients With ENOXaparin (MEDENOX) trial addressed
      this deficiency by assessing the need for and the benefit:risk ratio of
      thromboprophylaxis in a well-defined group of medical patients immobilized with
      severe illness. The MEDENOX study showed that these patients are at significant
      risk of VTE. Enoxaparin, 40 mg once daily for 6 to 14 days, reduced the risk of
      VTE by 63% without increasing adverse events. It is anticipated that data from
      the MEDENOX study will be incorporated into future consensus guidelines on the
      prevention of VTE. Further studies are required to assess the benefit:risk ratio
      of therapy in other clearly-defined medical groups.

PMID- 11449342
TI  - Unexplored territories in the nonsurgical patient: a look at pregnancy.
AB  - Venous thromboembolism (VTE) remains the most common cause of maternal death
      during pregnancy and the puerperium. The risk is increased in women older than 35
      years and those with obesity, previous VTE, operative delivery, and underlying
      thrombophilia. Anticoagulant therapy is indicated for short-term treatment of VTE
      and as thromboprophylaxis in high-risk patients. Warfarin is contraindicated
      during the first trimester because of fetotoxicity; unfractionated heparin (UFH)
      is associated with practical disadvantages and a risk of heparin-induced
      thrombocytopoenia (HIT) and osteoporosis with long-term use. Low-molecular-weight
      heparins (LMWHs) are convenient to use, do not cross the placenta, carry a lower
      risk of HIT and osteoporosis, and have been shown to be safe and effective during
      treatment of approximately 500 pregnant women. LMHWs are increasingly replacing
      UFH as the anticoagulant of choice during pregnancy; further studies are required
      to determine optimal therapeutic and thromboprophylactic doses. Women with
      inherited or acquired thrombophilia are at increased risk of severe pregnancy
      complications, including recurrent miscarriage, pre-eclampsia, fetal growth
      restriction, abruptio placentae, and stillbirth; uteroplacental microvascular
      thrombosis caused by thrombophilia appears to be the pathophysiologic link. LMWHs
      have been shown to improve pregnancy outcome in women with a history of obstetric
      complications and confirmed thrombophilia.

PMID- 11449343
TI  - Looking forward in the treatment of deep-vein thrombosis.
AB  - Clinical guidelines developed by the American College of Chest Physicians (ACCP)
      for the management of venous thromboembolism (VTE) are based on current evidence
      from randomized clinical trials and amended in response to emerging results. The
      standard treatment for VTE comprises in-hospital treatment with dose-adjusted
      unfractionated heparin (UFH) for a minimum of 5 days and oral anticoagulants for
      at least 3 months. Recent clinical studies show that subcutaneous low-molecular
      weight heparins (LMWHs) in fixed doses according to body weight are as effective
      and safe as intravenous UFH in the initial treatment of deep-vein thrombosis,
      with or without pulmonary embolism. There is also evidence that the optimal
      duration of secondary thromboprophylaxis depends on assessable thromboembolic
      risk factors. The 1998 ACCP guidelines take account of this new evidence by
      advocating LMWHs as an alternative to standard UFH for the initial treatment of
      VTE and risk stratification of patients to guide duration of secondary
      thromboprophylaxis. Outpatient treatment of VTE with LMWHs has been shown to be
      feasible and is increasingly used in clinical practice, offering substantial
      economic benefits. Certain LMWHs appear to be effective at a once-daily dose.
      Evidence is now emerging that may clarify the role of inferior vena cava filters
      and thrombolysis in VTE management. Future versions of the ACCP guidelines may be
      expected to reflect new data from ongoing trials.

PMID- 11449344
TI  - Clinical and economic aspects of managing venous thromboembolism in the
      outpatient setting.
AB  - Low-molecular-weight heparins (LMWHs) are at least as effective and safe as
      unfractionated heparin (UFH) in the prevention and initial treatment of venous
      thromboembolism (VTE), and their fixed-dose, once- or twice-daily dosing regimen
      without laboratory monitoring makes them suitable for outpatient use.
      Postoperative thromboprophylaxis usually continues until hospital discharge, but
      evidence demonstrates that the VTE risk persists for several weeks. Economic
      pressures, changes in clinical practice, and patient preferences make hospital
      stays shorter. As a result, outpatient thromboprophylaxis with LMWH has been
      investigated. LMWH self-administered at home once daily for up to 4 weeks after
      hospital discharge is safe and well tolerated and significantly reduces the
      incidence of postdischarge VTE after hip replacement. Targeted appropriately,
      extended thromboprophylaxis may be cost effective, and the development of an
      autoinjection device may increase the proportion of patients eligible for home
      management. LMWHs may also be of value as long-term secondary thromboprophylaxis
      in patients with contraindications to oral anticoagulants. Standard initial
      treatment for VTE comprises intravenous UFH administered to the patient in the
      hospital. However, three large-scale studies have demonstrated the efficacy and
      safety of outpatient treatment of acute VTE using LMWHs. The economic benefits of
      shortening or eliminating inpatient therapy are substantial, but successful home
      treatment requires careful patient selection, intensive education and a
      comprehensive system of professional support to optimize compliance and safety.

PMID- 11449345
TI  - Antithrombotic therapy in acute coronary syndromes: key notes from ESSENCE and
      TIMI 11B.
AB  - Platelet activation and thrombus formation are key events in the pathogenesis of
      acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction).
      Therefore, current management of these conditions consists of antithrombotic and
      antiplatelet therapy, principally heparin and oral aspirin. However, such
      treatment is unsuccessful in a significant proportion of patients. Two recent
      large studies with the low-molecular-weight heparin (LMWH) enoxaparin have shown
      that this agent significantly reduces the risk of major ischemic events compared
      with unfractionated heparin. In the Efficacy and Safety of Subcutaneous
      Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) study, treatment with
      enoxaparin for 2 to 8 days reduced the risk of death, myocardial infarction, or
      recurrent angina by 20% at 14 days compared with treatment with unfractionated
      heparin. In the Thrombolysis in Myocardial Infarction (TIMI) 11B study,
      enoxaparin was associated with a significant reduction in the risk of death,
      myocardial infarction, or urgent revascularization compared with unfractionated
      heparin, which became apparent within 48 hours; this benefit was maintained
      during outpatient treatment for 5 weeks. A meta-analysis of these two studies
      showed that the risk of death or myocardial infarction was consistently
      approximately 20% lower in enoxaparin-treated patients than in heparin-treated
      patients. In contrast, studies with other LMWHs have not shown consistent
      superiority over unfractionated heparin. This may reflect the pharmacologic
      heterogeneity of LMWH and/or differences in trial design.

PMID- 11449347
TI  - Soluble Fcgamma receptor IIIb alters the function of polymorphonuclear
      neutrophils but extends their survival.
AB  - We have established that polymorphonuclear neutrophil (PMN)-binding anti-Fcgamma
      receptor IIIb (FcgammaRIIIb) autoantibodies (autoAb) inhibit the function of
      these cells but extend their survival. Here, we show that recombinant
      FcgammaRIIIb (rFcgammaRIIIb), as well as purified FcgammaRIIIb (pFcgammaRIIIb),
      deteriorated the PMN adherence and respiratory burst in a dose-dependent manner.
      Furthermore, rFcgammaRIIIb and pFcgammaRIIIb reduced the level of annexin V
      binding PMN from 23.6 +/- 1.6 % to 6.3 +/- 1.0 and 11.0 +/- 1.0 %, respectively,
      while human serum albumin exerted no effects. Incubation of rFcgammaRIIIb with
      those autoAb binding to soluble FcgammaRIIIb resulted in the attachment of such
      immune complexes (IC) to the cells, thereby also delaying apoptosis (44.9 +/- 5.9
      versus 18.0 +/- 2.0 % annexin V-binding PMN after 16 hours). Soluble
      FcgammaRIIIb, in concert with FcgammaRIIIb / anti-FcgammaRIIIb IC, produced
      similar effects in that the percentage of annexin V-binding PMN declined to 16.0
      +/-1.9 %. It was thus suggested that FcgammaRIIIb / anti-FcgammaRIIIb IC inserted
      the Fc region of their IgG into the membrane FcgammaRIIIb. Such an interpretation
      is consistent with our finding that, whereas aggregated IgG and anti-FcgammaRIIIb
      monoclonal Ab prevented membrane FcgammaRIIIb / IC interaction, neither soluble
      FcgammaRIIIb, nor anti-cgammaRII did so. We conclude that the function and the
      life span of PMN are influenced synergistically by soluble FcgammaRIIIb and anti
      FcgammaRIIIb autoAb.

PMID- 11449348
TI  - Macrophage stimulation with Murabutide, an HIV-suppressive muramyl peptide
      derivative, selectively activates extracellular signal-regulated kinases 1 and 2,
      C/EBPbeta and STAT1: role of CD14 and Toll-like receptors 2 and 4.
AB  - The smallest unit of bacterial peptidoglycans known to be endowed with biological
      activities is muramyl dipeptide (MDP). A clinically acceptable synthetic
      derivative of MDP, namely murabutide (MB), has been found to present interesting
      pharmacological properties and to suppress HIV-1 replication in monocyte-derived
      macrophages (MDM). We have addressed the signaling events activated in MDM
      following stimulation with either MB or the potent immunostimulant LPS. We also
      examined whether signaling by muramyl peptides involves the use of cell surface
      receptors, including CD14 and Toll-like receptor 2 (TLR2) or TLR4 that are known
      to be signal-transducing receptors for other bacterial cell wall components. We
      demonstrate that, unlike LPS, the safe immunomodulator MB selectively activates
      extracellular signal-regulated kinases (Erk) 1/2, in the absence of detectable
      Jun N-terminal kinase (JNK) or p38 mitogen-activated kinase activation.
      Furthermore, STAT1 activation but weak or no activation of STAT3 or STAT5
      respectively, could be detected in MB-stimulated MDM. Using MonoMac6 cells, we
      observed high C/EBPbeta and AP-1 but weaker and transient NF-kappaB activation by
      MB.Moreover, the truncated form of C/EBPbeta, known to repress HIV-1
      transcription, was detected in extracts from MB-treated THP-1 cells.
      Surprisingly, neither MB nor MDP were able to transduce signals via CD14 and TLR2
      or 4. These findings present major differences in the early cell activation
      process between LPS and muramyl peptides, and strongly argue for the implication
      of co-receptors other than TLR2 and TLR4 in mediating the signaling events
      induced by defined subunits of bacterial peptidoglycans.

PMID- 11449349
TI  - Blimp-1 over-expression abrogates IL-4- and CD40-mediated suppression of terminal
      B cell differentiation but arrests isotype switching.
AB  - Following stimulation, primary B cells either directly undergo terminal
      differentiation to IgM-secreting plasma cells or enter the memory pathway
      characterized by affinity maturation and isotype switching. Which of the various
      fates is adopted by B cells is determined by the strength and duration of the
      antigenic signal, the availability and quality of T cell help and additional
      signals derived from the germinal center milieu. High rate secretion is
      correlated with endogenous Blimp-1 levels and can be caused by ectopic expression
      of Blimp-1. Using cultures of resting primary mouse B cells stimulated in vitro
      in various combinations with IL-4, anti-mu F(ab')2 or anti-CD40 in the absence or
      presence of lipopolysaccharide, we show that IgM secretion and the expression of
      Blimp-1 is either not induced or even suppressed by B cell receptors (BCR) or
      CD40 ligation and by IL-4. Additional treatment with IL-2 and IL-5 induces Blimp
      1 expression and facilitates IgM and IgG1 secretion, which can also be achieved
      by retroviral transduction of Blimp-1. On the other hand, the drastic increase in
      membrane IgG1(+) cells with time in cultures treated with IL-4 is greatly
      diminished in cells forced to express Blimp-1. We conclude that suppression of
      Blimp-1 by antigen-BCR interaction and T helper cell-dependent CD40 and IL-4
      signaling are necessary to facilitate entrance into the memory pathway and to
      prevent terminal differentiation.

PMID- 11449350
TI  - Neutrophils produce biologically active macrophage inflammatory protein-3alpha
      (MIP-3alpha)/CCL20 and MIP-3beta/CCL19.
AB  - Macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19 are
      members of the CC chemokine subfamily which exert their effects through specific
      receptors, CCR6 and CCR7, respectively. Previously, we have reported that human
      neutrophils have the capacity to produce a number of chemokines, including IL
      8/CXCL8, GROalpha/CXCL1, IP-10/CXCL10, and MIG/CXCL9. Herein, we show that
      neutrophils also have the ability to express and release MIP-3alpha/CCL20 and MIP
      3beta/CCL19 when cultured with either LPS or TNF-alpha. We also report that MIP
      3alpha/CCL20 and MIP-3beta/CCL19 production by LPS-stimulated neutrophils is
      negatively modulated by IL-10. Remarkably, we found that supernatants harvested
      from stimulated neutrophils not only induced chemotaxis of both immature and
      mature dendritic cells (DC), but also triggered rapid integrin-dependent adhesion
      of CCR6- and CCR7-expressing lymphocytes to purified VCAM-1 and ICAM-1,
      respectively. Importantly, both chemotaxis and rapid integrin-dependent adhesion
      were dramatically suppressed by anti-MIP-3alpha/CCL20 and anti-MIP-3beta/CCL19
      neutralizing antibodies, indicating that MIP-3alpha/CCL20 and MIP-3beta/CCL19
      present in the supernatants were both biologically active. As these chemokines
      are primarily chemotactic for DC and specific lymphocyte subsets, the ability of
      neutrophils to produce MIP-3alpha/CCL20 and MIP-3beta/CCL19 might be significant
      in orchestrating the recruitment of these cell types to the inflamed sites and
      therefore in contributing to the regulation of the immune response.

PMID- 11449351
TI  - A synthetic malaria vaccine elicits a potent CD8(+) and CD4(+) T lymphocyte
      immune response in humans. Implications for vaccination strategies.
AB  - We report the first synthetic peptide vaccine eliciting strong CD8(+) and CD4(+)
      T lymphocyte responses in humans. The vaccine, representing the C-terminal region
      of the circumsporozoite protein of Plasmodium falciparum (amino acids 282-383)
      was well tolerated and strong sporozoite-specific antibodies were elicited. In
      addition, robust lymphocyte proliferation responses were equally elicited with
      concomitant in vitro production of IFN-gamma, crucial in the elimination of the
      parasite. Most importantly, we also observed the development of CD8(+) T
      lymphocyte responses decisive in the immunity to malaria. The latter finding
      opens new, possibly safer, avenues for vaccination strategies when a CD8(+) T
      cell response is needed.

PMID- 11449352
TI  - The VpreB protein of the surrogate light-chain can pair with some mu heavy-chains
      in the absence of the lambda 5 protein.
AB  - Nineteen different mu heavy-chains, seven of them not capable of forming a pre B
      cell receptor were expressed in Drosophila melanogaster Schneider cells together
      with either VpreB1, VpreB2, lambda5, or the complete surrogate light-chain to
      study their interactions in the formation of the pre B cell receptor. The lambda5
      protein alone was unable to bind properly to any of the mu heavy-chains, while
      the VpreB proteins alone formed complexes with five of the mu heavy-chains. All
      mu heavy-chains incapable of forming a pre B cell receptor with surrogate light
      chain were also incapable of complex formation with VpreB. The possible role of
      the VpreB/mu heavy-chain in allelic exclusion of the heavy-chain locus during B
      cell development is discussed.

PMID- 11449353
TI  - Comprehensive analysis of the frequency of recognition of melanoma-associated
      antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): implications for
      immunotherapy.
AB  - Fifty-nine tumor-infiltrating lymphocyte (TIL) cultures established from melanoma
      invaded lymph nodes were screened for recognition of 28 melanoma-associated
      antigens (MAA) in association with31 HLA molecules. Twenty-three (39%) TIL lines
      reacted to at least one melanoma antigen. Melanosomal proteins were recognized by
      19 TIL populations and the most prominent responses against these proteins were
      directed against Melan-A/MART-1 (mainly in association with HLA-A*0201) and gp100
      (in association with diverse HLA contexts). Ten TIL populations reacted against
      10 tumor-specific antigens, in association with 8 different HLA molecules. HLA
      A*0201 and B*3501-restricted responses were the most frequent with, respectively,
      17 and 7 responses directed against 5 distinct antigens. Unexpectedly, the
      recognition by TIL of different MAA was frequently restricted by a single HLA in
      individual tumors, and there was no evidence for the existence of dominant MAA
      epitopes between tumors,except for Melan-A/MART-1 antigen. This analysis also led
      to the detection of 21 new HLA-peptide complexes recognized by melanoma TIL. This
      study, which is to our knowledge the most comprehensive analysis of TIL
      specificity to tumor antigens, has several implications for the design of
      immunotherapeutic strategies based on immunization against selected tumor
      epitopes.

PMID- 11449354
TI  - The adaptor protein shc is involved in the negative regulation of NK cell
      mediated cytotoxicity.
AB  - The activation of protein tyrosine kinase(s) (PTK) is a critical event required
      for the development of NK cell-mediated cytotoxicity. Here we demonstrate that
      the adaptor protein shc undergoes tyrosine phosphorylation during the generation
      of antibody-dependent cellular cytotoxicity (ADCC) and natural killing. In
      addition, we report that, upon direct or antibody-dependent target cell
      interaction, shc coprecipitates with the Src homology 2 (SH2)-containing inositol
      phosphatase, SHIP. To gain information on the functional role of shc in NK
      cytotoxicity, we overexpressed wild-type or dominant negative shc constructs in
      the human NKL cell line. Our findings show a consistent shc-mediated down
      regulation of ADCC and natural killing. Such functional effect correlates with a
      perturbation of the phosphoinositide (PI) metabolism by means of a shc-mediated
      negative regulation of inositol 1,4,5 triphosphate (IP3) generation and
      intracellular calcium flux upon CD16 ligation. Furthermore, our data show that
      dominant-negative shc-mediated perturbation of shc/SHIP interaction leads to
      inhibition of ligand-dependent SHIP recruitment to CD16 zeta chain. We suggest
      that shc plays a role of negative adaptor by modulating SHIP recruitment to
      activation receptors involved in the generation of NK cytotoxic function.

PMID- 11449355
TI  - Type I interferons and IL-12: convergence and cross-regulation among mediators of
      cellular immunity.
AB  - Therapeutic use of type I IFN (IFN-alpha/beta) has become common. Many of the
      diverse diseases targeted are marked by pathogenetic abnormalities in cell
      mediated immunity (CMI), these cellular immune responses either causing injury to
      the host, lacking sufficient vigor for virus or tumor clearance, or both. In
      general, therapeutic efficacy is limited. It is thus notable that the pleiotropic
      effects of type I IFN on CMI remain poorly understood. We characterized the
      effects of type I IFN on the production of IL-12, the central immunoregulatory
      cytokine of the CD4(+) T cell arm of CMI. We show that type I IFN are potent
      inhibitors of IL-12 production by human monocytes/macrophages. The underlying
      mechanism involves transcriptional inhibition of the IL-12p40 gene, marked by
      down-regulation of PU.1 binding activity at the upstream Ets site of the IL-12p40
      promoter. Type I IFN have previously been shown to be able to substitute for IL
      12 in driving IFN-gamma production from T and NK cells. The ability of IFN
      alpha/beta to suppress IL-12 production while up-regulating IFN-gamma production
      suggests a possible mechanistic basis for the difficulties of employing these
      cytokines in diseases involving abnormalities of CMI.

PMID- 11449356
TI  - The role of calpain in caspase activation during etoposide induced apoptosis in T
      cells.
AB  - T cells treated with the drug etoposide undergo apoptotic death characterized by
      early evidence of nuclear damage followed by loss of mitochondrial integrity and
      cell lysis. Calpains and caspases are cytoplasmic proteases and there is
      increasing evidence of cross-talk between these proteases in death pathways. In
      this study we have investigated the role of calpain, in etoposide-triggered
      apoptosis in the 2B4 murine T cell hybridoma. Cell permeable inhibitors of
      calpain, ALLnM, E64 and calpeptin that block Fas ligand-Fas-mediated death in T
      cells, blocked etoposide-induced nuclear damage, loss of mitochondrial integrity
      and cell lysis. A broad spectrum peptide inhibitor of caspases, ZVAD-fmk,
      partially blocked nuclear damage but poorly inhibited mitochondrial damage or
      cell lysis triggered by etoposide. Etoposide-induced expression of the cleaved,
      proteolytically active form of caspase 3, and DEVD-ase activity, detected prior
      to nuclear damage, were blocked in the presence of calpain inhibitors.
      Collectively, these data describe a role for calpain in regulating etoposide
      induced apoptosis via a caspase-dependent pathway in T cells.

PMID- 11449357
TI  - A regulatory role for cytoplasmic YVKM motif in CTLA-4 inhibition of TCR
      signaling.
AB  - CTLA-4 negatively regulates TCR signaling, although the molecular basis for this
      effect has yet to be elucidated. The cytoplasmic YVKM motif, while binding to
      phosphatidylinositol 3-kinase, SHP-2 and the AP-1/AP-2 clathrin adaptor
      complexes, has been reported to play no role in CTLA-4 function. In contrast, in
      this study, we demonstrate that, although not essential, the YVKM motif
      contributes to optimal CTLA-4 blockage of TCRzeta or combined TCRzeta/CD28
      signaling. Significantly, dependency on the YVKM motif varied with the mode of
      anti-receptor presentation, where soluble antibody ligation was more dependent on
      the presence of the motif than immobilized antibody. Previous studies have mainly
      relied on the use of immobilized antibody. Neither SHP-2 binding, alterations in
      TCRzeta chain phosphorylation, nor ZAP-70 recruitment was involved in CTLA-4 wild
      type or mutant inhibition. Overall, our findings clearly implicate the YVKM motif
      in optimal CTLA-4 function.

PMID- 11449358
TI  - Heat shock proteins as "danger signals": eukaryotic Hsp60 enhances and
      accelerates antigen-specific IFN-gamma production in T cells.
AB  - The heat shock proteins (HSP) gp96, Hsp70 and Hsp60 activate professional antigen
      presenting cells (APC) to secrete proinflammatory cytokines and to express
      costimulatory molecules. Here, we analyze the impact of Hsp60 as a hypothetical
      danger signal on the antigen-specific activation of T cells derived from DO11.10
      TCR-transgenic mice. The release of IFN-gamma, induced by the antigenic OVA(323
      339)-peptide, is increased and accelerated dramatically by the addition of Hsp60
      to ex vivo purified populations of T cells and peritoneal macrophages (PEC),
      while the antigen-specific IL-2 production or proliferation of the T cells remain
      unchanged. In contrast, "effector" T cells, undergoing secondary stimulation,
      displayed almost unchanged activation kinetics in the presence of Hsp60. The
      presence of Hsp60 induces IFN-gamma and up-regulation of CD69 in T cell/PEC
      cocultures even in the absence of antigenic peptide and this induction of IFN
      gamma is strictly dependent on the ability of the macrophages to produce IL-12.
      Taken together, our data strongly suggest that the presence of eukaryotic
      mitochondrial Hsp60 allows antigen-specific IFN-gamma secretion under conditions
      when an antigenic stimulus alone is not sufficient to activate T cells.

PMID- 11449359
TI  - Nramp1 modulates iron homoeostasis in vivo and in vitro: evidence for a role in
      cellular iron release involving de-acidification of intracellular vesicles.
AB  - Nramp1 controls responses to infection and encodes a biallelic (G169D) macrophage
      restricted divalent-cation transporter. Nramp1(D169) is phenotypically null. We
      demonstrate Nramp1 is implicated in iron regulation in vivo. In spleen,
      expression is exclusive to Nramp1(G169) strains within the red pulp. By
      morphometric analysis, the distribution of splenic iron, following systemic
      overload, correlates with Nramp1 genotype. More iron is located within the red
      pulp in Nramp1(D169) strains, whereas in Nramp1(G169) strains iron deposits are
      localized within the marginal-zone metallophilic cells. Nramp1 immunoreactive
      protein is not present in control brain, but inducible within a hemorrhagic
      lesion model in Nramp1(G169) strains. Nramp1 protein expression demonstrates an
      inverse correlation to the presence of iron. Nramp1(G169) strains show no Perl's
      stain-reactive iron within the lesion. In contrast, Nramp1(D169) strains display
      iron-staining cells. The process of cellular iron regulation was investigated in
      vitro in Nramp1(G169) transfectant Raw264.7 macrophages. Greater (30-50%) iron
      efflux from Nramp1(G169) compared with Nramp1(D169) cells was determined. The
      extent of Nramp1-dependent iron-release was influenced by bafilomycin A1, and
      endogenous nitric oxide synthesis, both inhibitors of vacuolar-ATPase. This study
      demonstrates that Nramp1 regulates macrophage iron handling, and probably
      facilitates iron release from macrophages undergoing erythrophagocytosis in vivo.

PMID- 11449360
TI  - Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic
      T lymphocyte responses by therapeutic vaccination in the trimera mouse model of
      chronic HBV infection.
AB  - Humanized BALB/c mice (termed trimera mice) conditioned by lethal total body
      irradiation and bone marrow transplantation from SCID mice have been described to
      support rapid engraftment of human peripheral blood mononuclear cells (PBMC) and
      the induction of strong B and T cell responses after immunization in vivo.
      Moreover, these mice can be infected with the hepatitis B and C viruses (HBV,
      HCV). The current study employed this model to study therapeutic vaccination
      approaches against the HBV. Thus, strong primary Th cell responses against the
      HBV core (HBc) and the Borrelia burgdorferi control antigen were induced by
      transfer of antigen-loaded dendritic cells together with autologous PBMC from HBV
      naive donors as well as by vaccination with high doses of antigen or a DNA
      plasmid encoding for HBcAg. Moreover, primary peptide-specific CTL responses
      against the immunodominant epitope HBc(18 - 27) were induced by HBc particle or
      DNA vaccination of chimera engrafted with HBV-naive PBMC. Finally, strong HBc
      specific Th cell and antibody responses were induced by HBc or DNA vaccination of
      mice reconstituted with PBMC from a chronic HBV patient. Thus, since HBc
      represents the immunodominant antigen in self-limited HBV infection, HBc
      particles or DNA vectors are good candidates for therapeutic vaccination, that
      will be further studied in our model and clinical studies.

PMID- 11449361
TI  - T early alpha (TEA) regulates initial TCRVAJA rearrangements and leads to TCRJA
      coincidence.
AB  - Both TCRA alleles are rearranged in mature T lymphocytes, as a result of a lack
      of allelic exclusion at the TRCA locus. We show in a series of T cell clones that
      the two TCRJA segments are not randomly, but rather coincidentally, rearranged in
      a given T cell. The TCRJA coincidence relies, in part, on the presence of "T
      early alpha" (TEA), a cis-regulatory genetic element located upstream of the
      TCRJA cluster. TEA promotes specific recombinational accessibility that targets
      primary TCRVAJA rearrangements on the 5' side of the TCRA locus. In a model of
      multiple waves of TCRVAJA recombination, this cis-regulatory effect of TEA allows
      for the scanning of the entire TCRJA cluster, thereby increasing the TCR
      alpha/beta diversity potential.

PMID- 11449362
TI  - Intact B cell tolerance in the absence of the first component of the classical
      complement pathway.
AB  - A critical role for complement in the regulation of self tolerance has been
      proposed to explain the strong association between complement deficiency and
      autoimmunity. To elucidate the role of the classical pathway of complement in the
      maintenance of B cell tolerance, C1q-deficient (C1qa-/-) mice were bred with anti
      hen egg lysozyme (HEL) immunoglobulin (Ig(HEL)) and soluble HEL (sHEL) transgenic
      mice. B cell tolerance was intact in C1qa-/- mice. In vivo, double-transgenic
      (Ig(HEL)/sHEL) C1qa-/- and wild-type control mice down-regulated surface
      immunoglobulin expression on splenocytes and equivalent numbers of HEL-binding B
      cells accumulated in the periphery. Maturation of B cells, evidenced by CD21
      expression, was retarded to the same extent and at a similar time point. The
      frequency of anti-HEL-producing plasma cells and serum levels of anti-HEL
      immunoglobulin were comparably reduced in control and C1qa-/- double-transgenic
      mice compared to control Ig(HEL) and C1qa-/- Ig(HEL) mice. Furthermore,
      splenocytes from double-transgenic C1qa-/- or wild-type mice did not modulate
      intracellular calcium levels after stimulation with HEL in vitro. These data
      demonstrate that a stable form of B cell anergy persists in the periphery of C1qa
      /- mice, suggesting that activation of the classical pathway by C1q is not
      essential for the maintenance of B cell tolerance in this transgenic model.

PMID- 11449363
TI  - A T cell receptor transgenic model of severe, spontaneous organ-specific
      autoimmunity.
AB  - The development of mouse models of human organ-specific autoimmune diseases has
      been hampered by the need to immunize mice with autoantigens in potent adjuvants.
      Even autoantigen-specific T cell receptor transgenic models of autoimmunity have
      proven to be complex as the transgenic mice frequently fail to develop disease
      spontaneously. We have isolated a CD4(+) T cell clone (TxA23)that recognizes the
      gastric parietal cell antigen, H/K ATPase alpha-chain(630-641), from a mouse with
      autoimmune gastritis that developed after thymectomy on day 3 of life. The T cell
      receptor alpha and beta genes from this clone were used to generate A23
      transgenic mice. All A23 transgenic animals spontaneously developed severe
      autoimmune gastritis, and evidence of disease was detected as early as day 10 of
      life. Gastritis could be transferred to immunocompromised mice with a limited
      number of transgenic thymocytes (10(3)), but as many as 10(7) induced only mild
      disease in wild-type animals. Due to the complete penetrance of spontaneous
      disease, identity of the auto-antigen, susceptibility to immunoregulation, and
      close relation to autoimmune gastritis in man, A23 transgenic mice represent a
      unique CD4(+) T cell-mediated disease model for understanding the multiple
      factors regulating organ-specific autoimmunity.

PMID- 11449364
TI  - The protein tyrosine kinase inhibitor AG126 prevents the massive microglial
      cytokine induction by pneumococcal cell walls.
AB  - Central nervous system (CNS) infections caused by Streptococcus pneumoniae still
      have a disastrous outcome. Underlying immunological and CNS cellular events are
      largely enigmatic. We used pneumococcal cells walls (PCW) to investigate
      microglial responses as these cells are prominent sensors and effectors during
      neuropathological changes. PCW stimulation of mouse microglia in vitro evoked the
      release of the cyto- and chemokines, TNF-alpha, IL-6, IL-12, KC, MCP-1, MIP
      1alpha, MIP-2 and RANTES as well as soluble TNF receptor II, a potential TNF
      alpha antagonist. The release induction followed extremely steep dose-response
      relations, and short exposure periods (15 min) were already sufficient to trigger
      substantial responses. PCW signaling controlling the release depended on both p38
      and p42/p44 (ERK2/ERK1) MAP kinase activities. The kinase inhibitor, tyrphostin
      AG126 prevented the PCW-inducible phosphorylation of p42/p44(MAPK), potently
      blocked cytokine release and drastically reduced the bioavailable TNF-alpha,
      since it only marginally affected the release of soluble TNF receptors. Moreover,
      in an in vivo model of pneumococcal meningitis, AG126 significantly attenuated
      the PCW-induced leukocyte influx to the cerebrospinal fluid. The findings imply
      that pneumococcal CNS infection can cause a rapid and massive microglial
      activation and that ERK/MAPK pathway(s) are potential targets for pharmacological
      interventions.

PMID- 11449365
TI  - Gut-derived effector T cells circulating in the blood of the rat: preferential re
      distribution by TGFbeta-1 and IL-4 maintained proliferation.
AB  - Effector T cells generated in mesenteric lymph nodes (mLN) preferentially
      accumulate in mLN and sites drained by them, such as Peyer's patches and the
      lamina propria of the gut, after circulation in the blood. The molecular
      mechanisms mediating this re-distribution are poorly understood. To study this,
      rat T cells from mLN were activated via the T cell receptor and CD28, and
      injected either intravenously into congenic recipients, or maintained in culture
      in the presence of various cytokines. Three days later effector T cells were
      identified in vivo and in vitro, and surface molecule expression and
      proliferation rate was determined. The data show that in vivo effector mLN T
      cells express significantly higher levels of activation markers and maintain a
      higher proliferation rate after entering the mLN environment (tissue of origin)
      than after entering the peripheral LN environment (unrelated site). The
      proliferation is mediated by TGFbeta-1 and IL-4 present in mLN. The requirement
      for these cytokines is imprinted on effector mLN T cells during the initial
      activation. Thus, the preferential proliferation of effector mLN T cells in
      milieus providing the cytokine mixture experienced during activation ensures a
      privileged accumulation at sites where they are most needed. This can be used to
      manipulate the effector phase of an immune response.

PMID- 11449366
TI  - Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM
      tyrosine of Ig-alpha.
AB  - The cytoplasmic adaptor protein SLP-65 (BLNK or BASH) is a critical downstream
      effector of the B cell antigen receptor (BCR). Tyrosine-phosphorylated SLP-65
      assembles intracellular signaling complexes such as the Ca(2 +) initiation
      complex encompassing phospholipase C-gamma2 and Bruton's tyrosine kinase. It is,
      however, unclear how the SLP-65 signaling module can be recruited to the plasma
      membrane. Here we show that following B cell stimulation, SLP-65 associates
      directly with the BCR signaling subunit, the Ig-alpha / Ig-beta heterodimer. The
      interaction is mediated by the Src homology 2 domain of SLP-65 and the
      phosphorylated Ig-alpha tyrosine 204, which is located outside of the
      immunoreceptor tyrosine-based activation motif. Our data identify an unexpected
      BCR phosphorylation pattern and indicate that Ig-alpha has the capability to
      serve as transmembrane adaptor in BCR signaling.

PMID- 11449367
TI  - The glucocorticoid inhibition of LFA-1 and CD2 expression by human mononuclear
      cells is reversed by IL-2, IL-7 and IL-15.
AB  - Glucocorticoids are agents endowed with powerful immunosuppressive and anti
      inflammatory properties partially related to the inhibition of adhesion-related
      processes. We have previously demonstrated that glucocorticoids inhibit LFA-1 and
      CD2 expression in human peripheral blood mononuclear cells (PBMC) by down
      regulating mRNA steady-state levels. In this study, we investigated whether
      glucocorticoids could also act indirectly by modulating the effect/function of
      cytokines whose expression are known to inhibit. To test this hypothesis, we
      replenished the following cytokines IL-2, IL-7, IL-15, TNF-alpha, IL-1beta, IL-4
      and IL-10, in an in vitro PBMC culture system. Our results indicate that only the
      IL-2Rgamma-chain-dependent cytokines IL-2, IL-7 and IL-15, among the cytokines of
      this panel, could reverse the inhibition of glucocorticoids on PBMC adhesion
      molecule expression and the related functions of intercellular aggregation and
      proliferation. Furthermore, we also demonstrated that IL-2, IL-7 and IL-15 could
      induce de novo the synthesis of LFA-1 and CD2. Taken together, these data suggest
      that glucocorticoids inhibit PBMC LFA-1 and CD2 expression not only directly by
      modulating transcriptional events, but also indirectly through the inhibition of
      IL-2Rgamma-dependent cytokines.

PMID- 11449368
TI  - The primary IgM antibody repertoire: a source of potent idiotype immunogens.
AB  - A widely held view is that, to elicit adaptive immune responses, most protein
      antigens must be given with adjuvants that activate the innate immune system. It
      has also been proposed that the immune system is tolerant to idiotypes (Id) of
      the syngeneic primary antibody (Ab) repertoire. We now show that among 73
      purified noncomplexed secretory IgM monoclonal antibodies (mAb), 4 (5.5%)
      elicited high levels of IgG Ab against the Id even though no adjuvant was added.
      The responses were controlled by H2-linked immune response genes. IgG1, but no
      IgG2a or IgG2b, anti-Id Ab were detected, indicating involvement of T helper type
      2 (Th2) cells. All 4 IgM mAb are likely germ-line gene-encoded, and 1 was shown
      to represent a recurrent Id. After endotoxin depletion the most potent immunogen
      of the 4 still provoked robust humoral anti-Id responses. The results suggest
      that a natural protein of the primary IgM Ab repertoire can be immunogenic
      without an adjuvant.

PMID- 11449369
TI  - Identification of CpG oligonucleotide sequences with high induction of IFN
      alpha/beta in plasmacytoid dendritic cells.
AB  - The immature plasmacytoid dendritic cell (PDC) is identical with the principal
      type I IFN-producing cell upon viral infection. Oligodeoxynucleotides which
      contain unmethylated CpG motifs (CpG ODN) are recognized by the vertebrate immune
      system. Previously, we described CpG ODN that strongly activate human B cells and
      human blood dendritic cells. Here we describe distinct CpG-containing
      oligonucleotide sequences which, in contrast to previously described CpG ODN,
      induced high amounts of IFN-alpha and IFN-beta in peripheral blood mononuclear
      cells (PBMC). Intracellular staining for IFN-alpha revealed that within PBMC CpG
      ODN-induced IFN-alpha is produced exclusively by PDC. Unlike IFN-alpha, TNF-alpha
      is up-regulated in PDC by all CpG ODN tested. Purified PDC responded to CpG ODN,
      demonstrating direct activation of PDC by CpG ODN. The most active sequence
      induced the production of up to 5 pg IFN-alpha per single PDC, resulting in more
      than 400 ng/ml IFN-alpha in the supernatant of PBMC enriched for PDC. The potency
      of CpG ODN to stimulate IFN-alpha correlated with their ability to stimulate NK
      cell lytic activity, while purified NK cells did not respond to CpG ODN. IFNgamma
      production in PBMC was dependent on CpG ODN-induced IFN-alpha/beta as
      demonstrated by IFN-alpha/beta blocking antibodies. IFN-alpha-inducing CpG ODN
      strongly supported IFN-gamma production of TCR-triggered CD4 T cells but were
      less active than other CpG ODN in stimulating B cells. In conclusion our results
      demonstrate that particular CpG ODN sequences exist which, due to high IFN
      alpha/beta induction in PDC, induce a set of immune responses typical for viral
      infection.

PMID- 11449370
TI  - The absence of SLP65 and Btk blocks B cell development at the preB cell receptor
      positive stage.
AB  - Mice deficient for the adapter protein SLP65 (BLNK) show a partial block in early
      B cell development, reduced numbers of mature B cells in the periphery, an
      absence of B1 cells and a reduction of IgM and IgG3 serum immunoglobulin levels.
      A strikingly similar phenotype is observed in Btk-deficient mice. To investigate
      the consequences of mutations in both SLP65 and Btk, we generated SLP65/ Btk
      double-mutant mice by crossing the single-mutant mice. Analysis of the double
      mutant mice reveals a much more severe defect in B cell development. B cells in
      the SLP65/Btk double-mutant mice are arrested at the preB cell stage and,
      surprisingly, express the preB cell receptor. Normally, preB cell receptor
      expression in wild-type mice is restricted to a very small fraction of B cells
      making it difficult to identify these cells in the bone marrow. Together, the
      data demonstrate the synergistic role of SLP65 and Btk in B cell development and
      describe a situation where large numbers of preB cell receptor-positive cells
      accumulate in the bone marrow and spleen.

PMID- 11449371
TI  - Diverging binding capacities of natural LD78beta isoforms of macrophage
      inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their
      anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils.
AB  - Recently, the LD78beta isoform of the CC chemokine macrophage inflammatory
      protein (MIP)-1alpha was shown to efficiently chemoattract lymphocytes and
      monocytes and to inhibit infection of mononuclear cells by R5 HIV-1 strains. We
      have now demonstrated that after cleavage of the NH2-terminal Ala-Pro dipeptide
      by CD26, LD78beta(3 - 70) became the most potent chemokine blocking HIV-1.
      LD78beta(3 - 70) competed tenfold more efficiently than LD78beta(1 - 70) with
      [125I] RANTES for binding to the CC chemokine receptors CCR5 and CCR1. Contrary
      to LD78alpha, LD78beta(1 - 70) at 30 ng/ml efficiently competed with [125I]
      RANTES for binding to CCR3 and mobilized calcium in CCR3 transfectants, whereas
      LD78beta(3 - 70) showed a 30-fold decrease in CCR3 affinity compared to
      LD78beta(1 - 70). This demonstrates the importance of the penultimate proline in
      LD78beta(1 - 70) for CCR3 recognition. Both LD78beta isoforms efficiently
      chemoattracted eosinophils from responsive donors. In contrast, only the CCR3
      agonist LD78beta(1 - 70) and not LD78beta(3 - 70), induced calcium increases in
      eosinophils with low levels of CCR1. In responder neutrophils, LD78beta(3 - 70)
      elicited calcium fluxes at a 30-fold lower dose (10 ng/ml) compared to intact
      LD78beta and LD78alpha, whereas the three MIP-1alpha isoforms were equipotent
      neutrophil chemoattractants. Taken together, both LD78beta isoforms are potent
      HIV-1 inhibitors (CCR5) and activators for neutrophils (CCR1) and eosinophils
      (CCR1, CCR3), affecting infection and inflammation.

PMID- 11449372
TI  - Osteoclastogenesis is enhanced by activated B cells but suppressed by activated
      CD8(+) T cells.
AB  - Host immune response is known to contribute to the progression of periodontitis,
      and alveolar bone destruction in periodontitis is associated with enhanced
      osteoclast activity. Therefore, we evaluated the roles of activated lymphocyte
      subsets in osteoclastogenesis. Osteoclast precursors were co-cultured with
      activated lymphocytes (B, CD4(+) T, CD8(+) T) in the presence of either
      macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus soluble receptor
      activator of NF-kappaB ligand (sRANKL), and subsequent differentiation into
      active osteoclasts was evaluated by a resorption assay. The activated B and
      CD4(+) cells, but not CD8(+) T cells, induced osteoclast differentiation in the
      presence of M-CSF alone. In the presence of M-CSF and sRANKL, B cells induced the
      formation of small but highly active osteoclasts and increased resorption, while
      CD8(+) T cells profoundly suppressed osteoclastogenesis. Co-culture using an
      insert well or supernatant suggested that both B and CD8(+) T cells acted on
      osteoclasts mostly via soluble proteins. Activated B cells expressed many
      osteoclastogenic factors including RANKL, TNF-alpha, IL-6, MIP-1alpha, and MCP-3.
      CD8(+) T cells expressed a substantial amount of osteoprotegerin (OPG) along with
      RANKL. However, blocking antibody to OPG did not reverse the suppression by
      CD8(+) T cells, suggesting that other factor(s) are involved. Taken together,
      activated B cells promoted osteoclastogenesis, while CD8(+) T cells inhibited the
      osteoclast formation via direct interaction. The results imply the importance of
      lymphocyte subpopulations in the development of periodontitis.

PMID- 11449373
TI  - IgM and stromal cell-associated heparan sulfate/heparin as complement-independent
      ligands for CD19.
AB  - The more severe phenotype of mice lacking CD19 as compared to CD21 suggests that
      a complement-independent ligand for the CD19/CD21 complex exists. We sought
      ligands for CD19 by examining binding reactions with fusion proteins comprised of
      the extracellular region of CD19 and the Fc region of IgG1. A fusion protein
      containing the third extracellular domain (D3-Fc) bound to WEHI-231 cells, and
      this was competed by soluble IgM. This function of IgM was confirmed by the
      binding of D3-Fc to beads coated with IgM. A second ligand for D3-Fc was found on
      stromal cells, and was shown to be heparin/heparan sulfate. These two ligands
      would be considered to reside on follicular dendritic cells, and may account for
      the observed ability of D3-Fc to bind to sites in germinal centers containing
      these cells.

PMID- 11449374
TI  - Long synthetic peptides encompassing the Plasmodium falciparum LSA3 are the
      target of human B and T cells and are potent inducers of B helper, T helper and
      cytolytic T cell responses in mice.
AB  - We synthesized 17 long synthetic peptides (LSP) spanning the whole 200-kDa
      Plasmodium falciparum liver stage antigen-3 (LSA3), an antigen that induces
      protection in chimpanzee, and analyzed their immunogenicity in BALB/c mice and
      their antigenicity in individuals living in a hyper-endemic malaria area. Our
      findings show that both specific antibodies and T cell proliferation against most
      LSA3-LSP develop in malaria-exposed adults. All individuals studied had
      detectable antibodies against a minimum of 6 and a maximum of 15 polypeptides. It
      is noteworthy that antibody prevalence and titers were as high against non-repeat
      as repeat regions. Although the extent of T cell reactivity was lower than that
      observed for B cells, most of the sequences contained at least one T helper
      epitope, indicating that the majority of LSA3-LSP contain both B and T cell
      epitopes within the same sequence. Injection of LSA3-LSP with SBSA2 adjuvant in
      mice, showed strong immunogenicity for most of them, eliciting both T cell
      responses and specific antibody production. While all the peptides were
      immunogenic for B cells, different patterns of T cell responses were induced.
      These peptides were thus classified in three sets according to the levels of the
      T cell proliferative and of the IFN-gamma-specific responses. Importantly,
      antibodies and T cells against some of the LSP were able to recognize LSA3 native
      protein on P. falciparum sporozoites. Additionally, some LSP (44-119, 1026-1095,
      1601-1712) also contained epitopes recognized by H-2(d) class I-restricted T
      cells. These results led to the identification of numerous domains that are
      highly antigenic and immunogenic within the LSA3 protein, and underline the value
      of the LSP approach for vaccine development.

PMID- 11449375
TI  - A monoclonal antibody against the immunodominant epitope of the ribosomal P2beta
      protein of Trypanosoma cruzi interacts with the human beta 1-adrenergic receptor.
AB  - Monoclonal antibodies were raised against a recombinant ribosomal P2beta protein
      of Trypanosoma cruzi. One of these reacted with the C terminus of this protein
      (peptide R13, EEEDDDMGFGLFD) and epitope mapping confirmed that this epitope was
      the same as the one defined by the serum of immunized mice, and similar to the
      previously described chronic Chagas' heart disease (cChHD) anti-P epitope.
      Western blotting showed that the monoclonal antibody recognized the parasite
      ribosomal P proteins, as well as the human ribosomal P proteins. Electron
      microscopy showed that it stained different structures in parasite and human
      cells. Interestingly, surface plasmon resonance measurements indicated that the
      affinity for the parasite ribosomal P protein epitope (R13) was five times higher
      than for its human counterpart (peptide H13, EESDDDMGFGLFD). Since the human
      epitope contained an acidic region (EESDD) similar to the AESDE peptide
      recognized by cChHD patients in the second extra-cellular loop of the human beta1
      adrenergic receptor, the biological activity of the antibody was assessed on
      neonatal rat cardiomyocytes in culture. The monoclonal antibody had an agonist
      like effect. These results, together with the fact that the monoclonal reacted in
      Western blots with the different isoforms of the heart beta1-adrenergic receptor,
      confirm the possible pathogenic role of antibodies against the parasite ribosomal
      P protein based on their cross-reaction with the human beta1-adrenergic receptor.

PMID- 11449376
TI  - Down-regulation of human alloimmune responses by genetically engineered
      expression of CD95 ligand on stimulatory and target cells.
AB  - Transgenic expression of apoptosis-inducing molecules could be a strategy to
      protect cells and tissues from destruction by apoptosis-susceptible effector T
      cells. Some evidence for the potency of this approach has been obtained in mouse
      and rat transplantation models. However, limited data are available on the
      capacity of apoptosis-inducing molecules to modulate human alloimmune responses.
      In this study we analyzed the in vitro consequences of an interaction of human T
      cells with allogeneic 293 cells and 293 transfectants stably expressing high
      levels of the apoptosis-inducing CD95 ligand (CD95L). Both, CD95L(-) and CD95L(+)
      293 cells were able to activate allogeneic T cells as demonstrated by comparable
      CD25 expression at day 2 of culture. The analysis of viable T cells at day 7,
      however, revealed anti-293 cytotoxic activity only in cultures that had been
      stimulated with CD95L(-) 293 cells. Alloactivated effector T cells lysed CD95L(-)
      and CD95L(+) 293 targets with similar efficiency when tested in a 4-h 51Cr
      release assay. Prolongation of the effector phase to 20 h resulted in a further
      increase in the destruction of CD95L(-) target cells, whereas lysis of CD95L(+)
      targets remained low. These data suggest that genetically engineered expression
      of CD95L on cells or tissues could be an approach to control human T cell
      reactivity towards allografts. During the induction of an alloimmune response
      depletion of cytotoxic precursor cells may be obtained by overexpressing CD95L on
      stimulatory cells; CD95L expression on graft tissue might limit T cell-mediated
      destruction of the transplant during the effector phase of the response.

PMID- 11449377
TI  - Early Th1/Th2 cell polarization in the absence of IL-4 and IL-12: T cell receptor
      signaling regulates the response to cytokines in CD4 and CD8 T cells.
AB  - Differentiation of developing T cells into the type 1 (IFN-gamma-producing) or
      type 2 (IL-4-producing) subsets is a central theme of immune regulation. The
      balance of IL-4 and IL-12 present during T cell activation has been considered
      the major influence on type 1 versus type 2 development. Here we show that CD4 T
      cells can become biased towards type 1 or type 2 phenotypes during their initial
      activation in the absence of IL-4 or IL-12. This type of regulation is dependent
      on the balance of MAPkinase, protein kinase C, and calcineurin signaling after
      TCR engagement. Later maturation of Th1 or Th2 effectors is dependent on IL-12 or
      IL-4. However Tc1 CD8 effector development is independent of IL-12, and Tc2 cell
      generation requires both appropriate TCR signals and IL-4 early in effector
      development. Using an altered peptide ligand to stimulate TCR transgenic T cells,
      we show that altered signaling regulates the numbers of CD8 cells capable of
      developing into Tc2 effectors, and also their responsiveness to IL-4. Together,
      the results support a two-stage model of differentiation in which intermediate
      cells biased towards the type 1 or type 2 pathways after activation, are
      subsequently matured in response to IL-12 or IL-4, respectively.

PMID- 11449378
TI  - IFN-alpha and IL-18 synergistically enhance IFN-gamma production in human NK
      cells: differential regulation of Stat4 activation and IFN-gamma gene expression
      by IFN-alpha and IL-12.
AB  - IFN-gamma, a product of NK and T cells, is a key cytokine contributing innate and
      adaptive immunity. IFN-gamma production is induced via direct cell-cell contacts
      with APC and IFN-gamma -producing cells or by cytokines. During microbial
      infections macrophage-derived IFN-alpha, IL-12, and IL-18 enhance IFN-gamma
      production and Th1 response. Here we show that IFN-alpha in combination with IL
      18 very efficiently induces IFN-gamma expression also in primary, nonactivated NK
      cells and in NK-92 cell line. Comparison of the kinetics of IFN-gamma mRNA
      expression in nonactivated NK cells, NK-92 cells and activated T cells stimulated
      with IFN-alpha or IL-12 revealed that, although both of these cytokines directly
      up-regulate IFN-gamma mRNA expression, its levels remain elevated much longer
      with IL-12 stimulation. In both NK cells and T cells, Stat4 is known to be
      critical in IL-12 and IFN-alpha signaling. We show that Stat4 activation is
      transient in cells stimulated with IFN-alpha, whereas IL-12 induces more long
      lasting activation of the transcription factor. This prolonged activation of IFN
      gamma gene by IL-12 may result in more efficient IFN-gamma production compared to
      that of IFN-alpha. Our results demonstrate that IFN-alpha and IL-18 are important
      innate cytokines in inducing NK cell IFN-gamma production.

PMID- 11449379
TI  - Introduction: in search of the meaning and utility of countertransference.

PMID- 11449380
TI  - A contemporary psychoanalytic model of countertransference.
AB  - Over the last 100 years, countertransference has evolved from a narrow construct
      referring to the analyst's transference to the patient to a jointly created
      phenomenon that is ever-present in the psychotherapeutic situation. In recent
      years, a myriad of theoretical perspectives have begun to converge around the
      view that countertransference is partly determined by the therapist's preexisting
      internal object world and partly influenced by feelings induced by the patient.
      Countertransference is now regarded as inevitable, and minor enactments of
      countertransference may provide valuable information about what is being
      recreated in the therapist-patient dyad. Self-disclosure of countertransference
      may be useful in some situations, but the sharing of some feelings will overwhelm
      patients and burden them in a way that may be destructive to the therapeutic
      process.

PMID- 11449381
TI  - Identifying the faces in the mirror: untangling transference and
      countertransference in self psychology.
AB  - Experienced psychotherapists realize that there are many levels of meaning behind
      much that is said during the therapeutic hour. The challenge for the competent
      professional is to become wise enough to learn what to ignore and sensitive
      enough to know what to emphasize. Sorting this out is at the heart of the
      practice of good psychotherapy. In this article, we will briefly share our
      thoughts on this rich but complicated interpersonal interaction using Kohutian
      self psychology theory to understand the role of countertransference in the
      process of conducting psychotherapy.

PMID- 11449382
TI  - Rational and irrational aspects of countertransference.
AB  - Countertransference in therapy stems from biological tendencies and social
      learning influences that involve mild or heavy prejudiced thinking, feeling, and
      behaving. Several reasons are given why it is almost inevitable and has both
      beneficial and destructive aspects-not either/or but both/and. It is hypothesized
      that therapists can well make good use of countertransference if they strive to
      employ it in a preferential, experimental rather than an absolutist musturbating
      manner.

PMID- 11449383
TI  - Feelings in context: countertransference and the real world in feminist therapy.
AB  - The concept of countertransference has been seen as problematic by feminist
      therapists. However, feminist therapy theory is intensely interested in the
      symbolic levels of the relationships between therapists and clients, with an
      emphasis on how the here and now social context informs and transforms those
      symbols. This article describes a feminist perspective on the therapist's
      symbolic relationships to clients, and the positive and challenging ramifications
      of those symbolic encounters.

PMID- 11449384
TI  - Connection: the double-edged gift of presence.
AB  - Questioning various implications of the conventional term countertransference,
      the author proffers the idea of client-inspired therapist contributions and gives
      several clinical examples.

PMID- 11449385
TI  - An experiential alternative to countertransference.
AB  - In an experiential alternative, the therapist and the client attend mainly to a
      "third thing" throughout the session instead of to one another. A case is
      presented in which the experiential alternative can offer some new, and perhaps
      interesting, uses of the therapist's personal reactions in comparison with the
      uses of countertransference and personal reactions of the therapist when
      therapist and client attend mainly to one another throughout the session. These
      new uses are presented and illustrated.

PMID- 11449386
TI  - Whither countertransference in couples and family therapy: a systemic
      perspective.
AB  - This study addresses various perspectives on transference and countertransference
      dynamics from the context of couples and family therapy. It considers the
      phenomena of countertransference in couple and family therapy and illustrates
      treatment with three specific kinds of patient populations: adult survivors of
      childhood incest who receive therapy with their partner; couples group therapy;
      and psychotherapists and their families. How supervisors help trainees recognize
      and deal with the transference and countertransference in clinical practice also
      is explored. These reciprocal phenomena are even more complex to identify and
      handle in couple and family treatment than in individual therapy.

PMID- 11449387
TI  - Clinical implications of research on countertransference: science informing
      practice.
AB  - This article presents a clinically oriented synthesis of research findings
      pertaining to countertransference (CT). Findings are organized around five
      therapy-relevant questions concerning the origins, triggers, manifestations,
      management, and effects of CT. To date, research has focused primarily on
      impediments posed by therapists' CT reactions and mechanisms for managing them.
      It is argued that future research needs to be directed toward better
      understanding how therapists can use CT to enhance their work with clients.

PMID- 11449388
TI  - Therapist countertransference: in search of common themes and empirical
      referents.
AB  - Throughout this issue on countertransference (CT) and elsewhere, the multiple
      terms used to describe CT events provide rich conceptual diversity, but also
      result in theoretical isolation and clinical compartmentalization. Our study and
      understanding of CT would benefit remarkably if we could agree on empirical
      therapist features that any CT conceptualization must target. Subsequent
      discussions of CT then could specify which of the respective empirical features
      are being addressed. Accordingly, I offer a descriptive framework that asserts
      that CT and its hypothesized subtypes (e.g., subjective and objective) can be
      detected empirically whenever a therapist's experiences and actions with a
      particular client assume one of several definable "deviations from baseline." If,
      in our clinical or research pursuits, we are to understand CT, we have to take
      the time to assess the necessary behavioral baselines for therapists and their
      clients.

PMID- 11449389
TI  - Familial influence on age of onset among siblings with Huntington disease.
AB  - In order to provide data relevant to a search for modifying genes for age of
      onset in Huntington disease, we examined the relationship between CAG number and
      age of onset in a total of 370 individuals from 165 siblingships, in two cohorts
      of siblings with Huntington disease: an American group of 144 individuals from 64
      siblingships, and a Canadian population of 255 individuals from 113 siblingships.
      Using a logarithmic model to regress the age of onset on the number of CAG
      triplets, we found that CAG number alone accounted for 65%-71% of the variance in
      age of onset. The siblingship an individual belonged to accounted for 11%-19% of
      additional variance. This adds to the previous evidence that there are familial
      modifiers of the age of onset, independent of the CAG number. Such modifiers may
      consist of additional genes, which could be the target of a linkage study. A
      linkage study is feasible with the cooperation of a number of major centers and
      may be made more efficient by concentrating on sibling pairs that are highly
      discordant for age of onset.

PMID- 11449390
TI  - Lack of association of the (AAAT)6 allele of the GXAlu tetranucleotide repeat in
      intron 27b of the NF1 gene with autism.
AB  - A novel allele of the GXAlu tetranucleotide repeat in intron 27b of the
      neurofibromatosis 1 (NF1) gene has recently been reported to be present in 4.7%
      of autistic patients but not in controls. We have found the novel GXAlu allele
      absent in 204 patients from the South Carolina Autism Project and 200 controls.
      The autism population studied includes a significant number of patients with
      hypotonia, stereotyped behaviors, or postural, gait, and motor abnormalities
      similar to those seen in the patients previously reported to possess the novel
      GXAlu allele. This suggests that the novel (AAAT)6 GXAlu allele is not associated
      with autism.

PMID- 11449391
TI  - Evidence supporting WNT2 as an autism susceptibility gene.
AB  - We examined WNT2 as a candidate disease gene for autism for the following
      reasons. First, the WNT family of genes influences the development of numerous
      organs and systems, including the central nervous system. Second, WNT2 is located
      in the region of chromosome 7q31-33 linked to autism and is adjacent to a
      chromosomal breakpoint in an individual with autism. Third, a mouse knockout of
      Dvl1, a member of a gene family essential for the function of the WNT pathway,
      exhibits a behavioral phenotype characterized primarily by diminished social
      interaction. We screened the WNT2 coding sequence for mutations in a large number
      of autistic probands and found two families containing nonconservative coding
      sequence variants that segregated with autism in those families. We also
      identified linkage disequilibrium (LD) between a WNT2 3'UTR SNP and our sample of
      autism-affected sibling pair (ASP) families and trios. The LD arose almost
      exclusively from a subgroup of our ASP families defined by the presence of severe
      language abnormalities and was also found to be associated with the evidence for
      linkage to 7q from our previously published genomewide linkage screen.
      Furthermore, expression analysis demonstrated WNT2 expression in the human
      thalamus. Based on these findings, we hypothesize that rare mutations occur in
      the WNT2 gene that significantly increase susceptibility to autism even when
      present in single copies, while a more common WNT2 allele (or alleles) not yet
      identified may exist that contributes to the disorder to a lesser degree.

PMID- 11449392
TI  - A family study of Tourette syndrome in Japan.
AB  - Although the mode of inheritance remains in doubt, twin and family studies
      conducted mostly in the United States and western Europe suggest that genetic
      factors play an important role in the transmission and expression of Tourette
      syndrome (TS). In an effort to evaluate population-based genetic differences, we
      generated risk estimates for first-degree relatives of TS probands in Japan using
      methods similar to those utilized in recent Western studies. The subjects were 52
      TS probands seen at an outpatient clinic of Tokyo University Hospital and their
      165 first-degree relatives. All probands and one or more first-degree relatives
      in each family were interviewed concerning the presence of tic and obsessive
      compulsive symptoms by expert clinicians. The age-corrected rates of TS, chronic
      motor tics, obsessive-compulsive disorder, and subclinical obsessive-compulsive
      symptoms in the first-degree relatives were 2.0%, 12.0%, 1.6%, and 7.0%,
      respectively. Rates of TS and related disorders in Japan appear to be much lower
      than those in recent Western family studies. If replicated, these data suggest
      that there may be differences in the nature and frequency of vulnerable alleles
      for TS and related disorders in the Japanese compared to European populations.

PMID- 11449393
TI  - No association between 5HT-2A and bipolar disorder irrespective of genomic
      imprinting.
AB  - Recent evidence that 5HT-2A may be subjected to genomic imprinting prompted us to
      examine a collection of Irish family trios (an affected individual and both
      parents) for evidence of an association between 5HT-2A and bipolar disorder.
      Family trios offer an advantage over case control studies in regard to genomic
      imprinting since with family trios it is possible to trace the path of alleles
      from the parents to the offspring. Using haplotype-based haplotype relative risk
      (HHRR) and transmission/disequilibrium (TDT) analyses, no evidence was found for
      an association of 5HT-2A with bipolar affective disorder under the assumption of
      no imprinting and of imprinting.

PMID- 11449394
TI  - Pregnancy and perinatal complications associated with risks for common
      psychiatric disorders in a population-based sample of female twins.
AB  - The association between pregnancy and perinatal complications (PPCs) and risks
      for adult psychiatric disorders other than psychoses has received relatively
      limited attention. In this study, we aim to characterize the associations between
      PPCs and risks for anxiety, affective, substance use, and eating disorders in a
      population-based sample of twins. Personal interviews were conducted with 1,806
      female twin subjects to assess their lifetime history of alcoholism, anorexia
      nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic
      disorder, simple phobias, and social phobias. PPCs were retrospectively assessed
      at personal interview with the subject's parents. The associations between PPCs
      and risks for psychiatric disorders are characterized using logistic regression.
      In this sample of twins, gestational age is associated with a significantly
      increased risk for anorexia nervosa and pregnancy complications are associated
      with a significantly increased risk for both anorexia nervosa and bulimia
      nervosa. Pregnancy and perinatal complications may be associated with an
      increased risk for eating disorders in women.

PMID- 11449395
TI  - Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes
      in a population sample of twins.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common, highly heritable
      syndrome of childhood characterized by problems with inattention, hyperactivity,
      and impulsivity. A variety of case control and family-based transmission
      distortion genetic studies of ADHD have focused on the possible involvement of
      polymorphisms of the DRD4 receptor gene. The majority of studies have examined
      the association of variously defined ADHD with an exon 3 polymorphism containing
      a variable number of imperfect 48 base pair repeats. Recently, McCracken et al.
      [2000: Mol Psych 5:531-536] reported an association of the DSM-IV primarily
      inattentive ADHD subtype with a 5' 120 base pair repeat polymorphism in the DRD4
      gene. In this report, we test for the possible association of these two
      polymorphisms with population-derived samples of DSM-IV ADHD subtypes.
      Furthermore, we extend previous studies by testing for associations with ADHD
      subtypes derived from latent-class analysis of interview responses. In contrast
      to most, but not all, previous studies, we failed to demonstrate any significant
      association of the exon 3 7-repeat allele with ADHD. Nor did we replicate the
      association of the 5'120 base pair repeat polymorphism. We do find a significant
      association of the exon 3 3-repeat allele with a novel talkative/impulsive latent
      class-defined subtype of ADHD.

PMID- 11449396
TI  - A genomewide linkage study of age at onset in schizophrenia.
AB  - There is strong evidence for a genetic contribution to age at onset of
      schizophrenia, which probably involves both susceptibility loci for schizophrenia
      and modifying loci acting independent of disease risk. We sought evidence of
      linkage to loci that influence age at onset of schizophrenia in a sample of 94
      affected sibling pairs with DSM-IV schizophrenia or schizoaffective disorder, and
      age at first psychiatric contact of 45 years or less. Individuals were genotyped
      for 229 microsatellite markers spaced at approximately 20 cM intervals throughout
      the genome. Loci contributing to age at onset were sought by a quantitative
      maximum-likelihood multipoint linkage analysis using MAPMAKER/SIBS. A
      nonparametric multipoint analysis was also performed. The genomewide significance
      of linkage results was assessed by simulation studies. There were six maximum
      likelihood LOD score peaks of 1.5 or greater, the highest being on chromosome 17q
      (LOD = 2.54; genomewide P = 0.27). This fulfils Lander and Kruglyak's [1995: Nat
      Genet 11:241-247] criteria for suggestive linkage in that it would be expected to
      occur once or less (0.3 times) per genome scan. However, this finding should be
      treated with caution because the LOD score appeared to be almost solely accounted
      for by the pattern of ibd sharing at one marker (D17S787), with virtually no
      evidence of linkage over flanking markers. None of the linkage results achieved
      genomewide statistical significance, but the LOD score peak on chromosome 13q
      (LOD = 1.68) coincided with the region showing maximum evidence for linkage in
      the study by Blouin et al. [1998: Nat Genet 20:70-73] of categorical
      schizophrenia.

PMID- 11449397
TI  - Association study of serotonin transporter gene regulatory region polymorphism
      and alcoholism.
AB  - Previous studies have indicated associations between a functional biallelic
      repetitive element in the 5' regulatory region of the serotonin transporter gene
      (5-HTTLPR) and alcoholic subjects who have either dissocial personality disorder
      or severe withdrawal symptoms. To replicate these associations under the
      hypothesis that genetic polymorphism plays some role in the susceptibility or
      vulnerability of some subgroup of alcoholics, the associations between alcoholic
      subjects' genetic polymorphisms, clinical characteristics, and personality traits
      were examined. This case control study comprised 697 alcoholic and 270 control
      subjects. A questionnaire focusing on family and social background, history of
      drinking and alcohol withdrawal, DSM-III-R criteria for the evaluation of
      psychiatric conditions, and Feighner's criteria for the lifetime diagnosis and
      assessment of overall severity of alcoholism was administered to 373 alcoholic
      subjects. Temperament and Character Inventory (TCI) and Sensation Seeking Scale
      (SSS) were used to evaluate the other 324 alcoholics. The frequency of the
      homozygous short allele was significantly higher in alcoholic binge drinkers than
      in nonbinge drinking alcoholics. There were no significant differences in the
      frequencies of either the 5-HTTLPR genotype or the short vs. long allele in
      alcoholic and control subjects. The alcoholics' 5-HTTLPR genotype and allele
      frequencies did not differ significantly by the severity of withdrawal symptoms
      or by the number of positive Feighner's diagnostic criteria. Although these
      results indicate an association between 5-HTTLPR and a subgroup of alcoholics
      characterized by binge drinking, the authors found no differences in SSS and TCI
      subscale scores for alcoholics with different 5-HTTLPR genotypes. Future studies
      of the association in other alcoholic population should take into account
      personality traits.

PMID- 11449398
TI  - Case control and family-based studies of tryptophan hydroxylase gene A218C
      polymorphism and suicidality in adolescents.
AB  - The association of suicidality with polymorphism A218C in intron 7 of tryptophan
      hydroxylase (TPH) gene remains controversial. The aim of this study was to use
      family-based methods to examine this association in adolescents in order to
      eliminate the difficulty of sampling a control group from the same ethnic
      population. Eighty-eight inpatient adolescents who recently attempted suicide
      were assessed by structured interview for detailed clinical history, diagnoses,
      suicide intent, suicide risk, impulsivity, aggression, and depression. DNA
      samples were collected from all subjects, from both biological parents of 40
      subjects and from one parent of 9 subjects; TPH allele frequencies were
      calculated and tested for association to phenotype, stratified by severity, using
      the haplotype relative risk (HRR) and transmission disequilibrium test (TDT)
      methods (n = 49). The frequencies were also compared for all the Jewish subjects
      (n = 84) to the known frequencies of these alleles in healthy Jewish populations.
      There was no significant allelic association of A218C polymorphism with suicidal
      behavior or other phenotypic measures according to the HRR method (chi-square =
      0.094; P = 0.76), the TDT (chi-square = 0.258; P = 0.61), or association analysis
      to known population frequencies (chi-square = 1.667, P = 0.19 for Ashkenazi, and
      chi-square = 0.810, P = 0.37 for non-Ashkenazi). Analysis of variance with the
      Scheffe test demonstrated a significant difference between CC and AA genotypes in
      suicide risk and depression among the patients (n = 88). The findings suggest
      that polymorphism A218C has no major relevance to the pathogenesis of adolescent
      suicidal behavior, but may have a subtle effect on some related phenotypes.

PMID- 11449399
TI  - Serotonin transporter gene polymorphisms are associated with anxiety-related
      personality traits in women.
AB  - Several studies have reported an association between anxiety-related personality
      traits and a promoter polymorphism in the human serotonin transporter (5-HTT)
      gene (5-HTT gene-linked polymorphic region, 5-HTTLPR). In the present study, a
      population of 251 subjects was assessed with the Karolinska Scales of Personality
      (KSP) and genotyped both for the 5-HTTLPR and for a variable number of tandem
      repeats polymorphism in the second intron of the same gene. The interpretation of
      previous studies has to some extent been confounded by the studied subjects
      differing with respect to ethnicity, sex, and age. To circumvent this problem,
      all included subjects were Caucasians, women, and born in the same year (1956).
      Associations were found between the 5-HTTLPR and four of the five anxiety-related
      KSP scales (psychic anxiety, muscular tension, psychasthenia, and lack of
      assertiveness), subjects being homozygous for the short allele displaying higher
      anxiety scores than those of the long/long or long/short genotype. In addition,
      an association was found between the intron 2 polymorphism and one anxiety
      related personality trait (somatic anxiety).

PMID- 11449400
TI  - Examining for association between candidate gene polymorphisms in the dopamine
      pathway and attention-deficit hyperactivity disorder: a family-based study.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a highly heritable childhood
      onset psychiatric condition characterized by developmentally inappropriate
      inattention, hyperactivity, and impulsiveness. The pathophysiology of ADHD is
      currently unknown. However, the therapeutic effects of stimulant medication
      together with findings from animal and neuroimaging studies as well as from
      several molecular genetic studies of the dopamine receptor D4 gene and dopamine
      transporter gene have implicated involvement of the dopaminergic system. To test
      the dopaminergic hypothesis further, we have looked for association between ADHD
      and alleles of seven dopamine-related candidate genes using a family-based
      association approach in a sample of 150 children diagnosed with ADHD. We tested
      polymorphisms in genes encoding three dopamine receptors (DRD3, DRD4, and DRD5)
      and four dopamine-relevant enzymes: tyrosine hydroxylase [tyrosine hydroxylase
      (TH)], dopamine beta hydroxylase (DbetaH), catechol-O-methyltransferase (COMT),
      and monoamine oxidase A (MAOA). We were unable to detect a significant
      association with any of the polymorphisms genotyped, although there was a trend
      for preferential transmission of the DRD5 148 bp marker allele and the MAOA 122
      bp marker allele. We conclude that none of the alleles we have tested makes a
      major contribution to ADHD, although much larger samples are required to exclude
      small effects.

PMID- 11449401
TI  - Attention-deficit hyperactivity disorder: a study of association with both the
      dopamine transporter gene and the dopamine D4 receptor gene.
AB  - Attention-deficit hyperactivity disorder (ADHD) is one of the most common
      psychiatric disorders of childhood. The role of genetic factors in its etiology
      is strongly supported by family, adoption, and twin studies. Several
      investigations have reported associations between ADHD and both the 7-repeat
      allele of the 48 bp VNTR at the DRD4 gene and the 10-repeat allele of the 40 bp
      VNTR at the DAT1 gene, but the results have been inconsistent. A sample of 81
      Brazilian ADHD children and adolescents and their parents were screened for these
      DRD4 and DAT1 VNTRs. An excess of the DRD4 7-repeat allele was observed when both
      ADHD probands and their parents were compared with an ethnically matched control
      sample (chi-square = 11.55, P = 0.03; chi-square = 12.17, P = 0.03,
      respectively). However, haplotype relative risk (HRR) analysis showed no
      preferential transmission of the DRD4 7-repeat allele. No evidence of association
      with the DAT1 polymorphism was detected by both approaches. Nevertheless, an
      interaction effect of both genes on ADHD hyperactive/impulsive dimension was
      observed (F = 4.68; P = 0.03). These results add to the group of studies that
      together suggest a small effect of these genes in the susceptibility to ADHD.

PMID- 11449402
TI  - Association of the tryptophan hydroxylase gene with smoking initiation but not
      progression to nicotine dependence.
AB  - We investigated the association between two markers in the seventh intron of the
      tryptophan hydroxylase gene (TPH C218A and C779A) in a population-based case
      control study of 780 genotyped subjects. As in prior studies, the two markers
      were in strong linkage disequilibrium. The phenotypes we studied were smoking
      initiation and progression to nicotine dependence. Allele, genotype, and
      estimated haplotype frequencies for each marker were highly significantly
      different for smoking initiation (P < 0.0004 for each comparison) and were
      nonsignificant for progression to nicotine dependence. An empirical test
      suggested that the positive results were unlikely to have resulted from
      population stratification. Our results are similar to those of Lerman et al.
      [2001: Am J Med Genet (Neuropsychiatr Genet) 105:000-000] in associating these
      TPH markers with a construct related to smoking initiation but dissimilar in the
      variable implicated. If these results replicate in other samples, the
      serotonergic system may be involved in the etiology of smoking initiation given
      the rate-limiting role of TPH in the biosynthesis of serotonin.

PMID- 11449403
TI  - Optimizing flow cytometric DNA ploidy and S-phase fraction as independent
      prognostic markers for node-negative breast cancer specimens.
AB  - Developing a reliable and quantitative assessment of the potential virulence of a
      malignancy has been a long-standing goal in clinical cytometry. DNA histogram
      analysis provides valuable information on the cycling activity of a tumor
      population through S-phase estimates; it also identifies nondiploid populations,
      a possible indicator of genetic instability and subsequent predisposition to
      metastasis. Because of conflicting studies in the literature, the clinical
      relevance of both of these potential prognostic markers has been questioned for
      the management of breast cancer patients. The purposes of this study are to
      present a set of 10 adjustments derived from a single large study that optimizes
      the prognostic strength of both DNA ploidy and S-phase and to test the validity
      of this approach on two other large multicenter studies. Ten adjustments to both
      DNA ploidy and S-phase were developed from a single node-negative breast cancer
      database from Baylor College (n = 961 cases). Seven of the adjustments were used
      to reclassify histograms into low-risk and high-risk ploidy patterns based on
      aneuploid fraction and DNA index optimum thresholds resulting in prognostic P
      values changing from little (P < 0.02) or no significance to P < 0.000005. Other
      databases from Sweden (n = 210 cases) and France (n = 220 cases) demonstrated
      similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009
      and P < 0.12 to P < 0.002, respectively. Three other adjustments were applied to
      diploid and aneuploid S-phases. These adjustments eliminated a spurious
      correlation between DNA ploidy and S-phase and enabled them to combine
      independently into a powerful prognostic model capable of stratifying patients
      into low, intermediate, and high-risk groups (P < 0.000005). When the Baylor
      prognostic model was applied to the Sweden and French databases, similar
      significant patient stratifications were observed (P < 0.0003 and P < 0.00001,
      respectively). The successful transference of the Baylor prognostic model to
      other studies suggests that the proposed adjustments may play an important role
      in standardizing this test and provide valuable prognostic information to those
      involved in the management of breast cancer patients.

PMID- 11449404
TI  - Distinctive patterns of Her-2/neu, c-myc, and cyclin D1 gene amplification by
      fluorescence in situ hybridization in primary human breast cancers.
AB  - BACKGROUND: Human solid tumors undergo clonal evolution as they progress, but
      evidence for specific sequences of genetic changes that occur in individual
      tumors and are recapitulated in other tumors is difficult to obtain. METHODS:
      Patterns of amplification of Her-2/neu, c-myc, and cyclin D1 were determined by
      fluorescence in situ hybridization (FISH) in relation to the presence of p53
      dysfunction and ploidy in 60 primary human breast cancers. RESULTS: We show that
      there are clusters of genophenotypic abnormalities that distinguish lobular
      breast cancers from nonlobular tumors; that cyclin D1 amplification occurs prior
      to the divergence of lobular breast cancers from nonlobular cancers; that p53
      dysfunction, Her-2/neu amplification, and c-myc amplification are characteristic
      features of nonlobular breast cancers, but not of lobular breast cancers; and
      that the frequencies of amplification of all three oncogenes examined increase
      progressively with increasing aneuploidy, but that each gene exhibits a different
      profile of increasing amplification in relation to tumor progression. Early
      amplification of c-myc appears to be an especially prominent feature of
      hypertetraploid/hypertetrasomic tumors. CONCLUSIONS: The data suggest that in
      tumors containing multiple abnormalities, these abnormalities often accumulate in
      the same cells within each tumor. Furthermore, the same patterns of accumulation
      of multiple genophenotypic abnormalities are recapitulated in different tumors.

PMID- 11449405
TI  - Comparative image and flow cytometric TUNEL analysis of fine needle samples of
      breast carcinoma.
AB  - The assessment of apoptosis in solid tumors is of interest because of its
      biological role in tumor evolution and response to therapy. A commonly used
      method for apoptosis measurement is the TUNEL 3' end-labeling technique, which
      has shown wide variations in results when applied to solid tumors. Thirty-one
      fine needle breast carcinoma samples were analyzed by fluorescent TUNEL assay and
      DNA content using image analysis and flow cytometry. TUNEL positivity, seen both
      in cells with apoptotic morphology and in a subset of morphologically normal
      cells, was categorized into five staining patterns and quantitated. Values for
      patterns of TUNEL-positive cells were compared with TUNEL positivity measured by
      flow cytometry. Flow cytometric quantitation showed a mean of 24.3% positive
      cells, which correlated (P < 0.02) with total positive cells (all patterns)
      measured by image (22.4%). Image analysis quantitation of morphologically
      apoptotic cells (4.2%) did not correlate with flow cytometric TUNEL positivity
      and the majority of TUNEL-stained cells were morphologically normal (17%). Image
      analysis allows discrimination of TUNEL-positive morphologically apoptotic and
      nonapoptotic cells, which are included in the total number of TUNEL-positive
      events measured by flow cytometry.

PMID- 11449406
TI  - Immunophenotypic analysis of HIV-infected children: alterations within the first
      year of life, changes with disease progression, and longitudinal analyses of
      lymphocyte subsets.
AB  - Perinatal infection with human immunodeficiency virus (HIV) results in tremendous
      activation of the pediatric immune system. An important component of
      understanding the pathogenesis of this disease is to characterize and quantify
      antigenic indicators of activation within the peripheral lymphocyte population.
      We measured T-lymphocyte activation and maturation antigens in a cohort of 112
      HIV-infected children treated with antiretroviral therapy according to the
      current standard of care. Changes in expression of CD95, HLA-DR, and CD45RO were
      evident in 22 HIV-infected children younger than 1 year of age. A comparison of
      phenotypic profiles of children in mild, moderate, and severe immune categories
      revealed perturbations of CD28, CD38, CD45RA, CD45RO, CD95, and HLA-DR. Finally,
      a novel analysis of 56 HIV-infected children based on the repeated collection of
      data over time (median of seven observations over 33 months) demonstrated a
      strong negative correlation between the percentage CD4 and the percentage of
      CD45RO, CD95, and HLA-DR on both CD4 and CD8 cells. Our data implicate persistent
      immune activation, beginning within the first year of life, as a major driving
      force in the pathogenesis of perinatally acquired HIV disease.

PMID- 11449407
TI  - Prospective clinical study comparing DNA flow cytometry and HPV typing as
      predictive tests for persistence and progression of CIN I/II.
AB  - A cohort of 70 consecutive women at a university hospital colposcopy clinic with
      untreated CIN I and CIN II (CIN I/II) confirmed by cytology and histology was
      followed for 1 year in the setting of a prospective trial. In the lesions, the
      presence of DNA from HPV types was examined by restriction fragment length
      polymorphism (RFLP) analysis. Aneuploid cell lines were demonstrated by aneuploid
      histograms generated by high-resolution DNA flow cytometry. HPV type 16 infection
      and the existence of aneuploid cell lines proved to be significant risk factors
      for CIN I/II lesions to persist or progress to CIN III in the 1-year follow-up
      period in the same cohort of patients. The relative risks and 95% confidence
      intervals (CI) were 1.81 (1.44-2.76) for aneuploid cell lines and 1.74 (1.10
      2.76) for HPV type 16 infection in CIN I/II lesions. As a predictive diagnostic
      test for CIN I/II lesions to persist or progress, the specificity and positive
      predictive value (PPV) for aneuploid histograms were 100% (CI, 73.5-100%) and
      100% (CI, 86.8-100%), respectively. The low sensitivity of 27.3% (CI, 14.9-42.8%)
      restricted the clinical application of the test, leaving 32 of 44 women with
      persisting or progressing CINI/II with diploid histograms. HPV type 16 positivity
      by FRLP had a PPV of 68.4% (CI, 43.5-87.4%) as a prognostic test. Six of 19 HPV
      16 infected women showed complete remission of their CIN lesion. A combination of
      the two tests did not provide any additional information.

PMID- 11449408
TI  - Evaluation of monensin and brefeldin A for flow cytometric determination of
      interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha in monocytes.
AB  - Flow cytometry has become a powerful technique to measure intracellular cytokine
      production in lymphocytes and monocytes. Appropriate inhibition of the secretion
      of the produced cytokines is required for studying intracellular cytokine
      expression. The aim of this study was to compare the capacity of cytokine
      secretion inhibitors, monensin and brefeldin A, in order to trap cytokine
      production (interleukin-1 beta [IL-1beta], IL-6, tumor necrosis factor-alpha [TNF
      alpha]) within peripheral blood monocytes. A two-color flow cytometric technique
      was used to measure intracellular spontaneous and lipopolysaccharide (LPS)
      stimulated IL-1beta, IL-6, and TNF-alpha production in monocytes (CD14+) of whole
      blood cultures. The viability of monensin-treated monocytes was slightly lower
      than that of brefeldin A-inhibited monocytes, as measured with propidium iodide
      (PI). The percentage of IL-6 and TNF-alpha-producing monocytes after 8 h of
      culture without stimulation revealed significant lower values for monensin
      treated than for brefeldin A-treated monocytes. The percentages for stimulated
      cells did not differ. The spontaneous intracellular production in molecules of
      equivalent soluble fluorochrome units (MESF) of IL-1beta, IL-6, and TNF-alpha
      after 8 h of culture was higher in brefeldin A than in monensin-inhibited
      monocytes. The LPS-stimulated intracellular production of IL-1beta, IL-6, and TNF
      alpha was increased in brefeldin A-inhibited monocytes. In conclusion, for flow
      cytometric determination of intracellular monocytic cytokines (IL-1beta, IL-6,
      and TNF-alpha), brefeldin A is a more potent, effective, and less toxic inhibitor
      of cytokine secretion than monensin.

PMID- 11449409
TI  - Report of the clinical practice task force survey of the clinical cytometry
      society.

PMID- 11449410
TI  - Variations of components of the plasminogen activation system with the cell cycle
      in benign prostate tissue and prostate cancer.
AB  - BACKGROUND: Components of the fibrinolytic system are involved in tumor cell
      invasion and metastasis. Previous investigations suggested a cell cycle-dependent
      expression of urokinase-type plasminogen activator (u-PA) in epithelial cells. In
      order to determine a correlation of cell cycle phases with the fibrinolytic
      system, we investigated the expression of u-PA, tissue-type plasminogen activator
      (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) in normal and tumor
      containing prostate extracts and analyzed a possible relationship with flow
      cytometry-determined proliferative activity of the samples. Cell cycle phases
      were correlated with fibrinolytic parameters in prostate tissue. METHODS: Samples
      were obtained from patients undergoing radical prostatectomy for prostate cancer
      and separated into two portions for DNA analysis and the detection of u-PA, t-PA,
      and PAI-1. Flow cytometric analysis was performed according to the Vindelov
      technique. The concentrations of u-PA, t-PA, and PAI-1 were determined from
      tissue extracts after homogenization by an enzyme-linked immunosorbent assay
      (ELISA) technique. RESULTS: Correlations of u-PA and t-PA expression with the
      frequency of G0/G1, S, G2M, S-phase fraction (SPF), and proliferation index (PI)
      for normal prostate and prostate cancer revealed no significant correlation. The
      only significant finding was observed in normal tissue revealing a positive
      correlation between PAI-1 expression and G0/G1 and a negative correlation with S
      phase, SPF, and PI. No dependence of PAI-1 expression on different cell phases
      was found in prostate cancer. Furthermore, no significant correlation of u-PA, t
      PA, and PAI-1 with cell cycles in organ-confined (<pT3a) and disseminated (> or =
      pT3a) tumors was found. No significant correlation in prostate cancer of
      components of the fibrinolytic system differentiated according to tumor grade or
      perineural tumor infiltration and cell cycle analysis was found. Only in highly
      differentiated G1 (Gleason 2-4) cancer, u-PA had a significant positive
      correlation with G2M-phase. CONCLUSION: Absence of a correlation between levels
      of components of the fibrinolytic system and cell cycle phases suggests that the
      reported association between increases of some of these components and aggressive
      biological behavior of prostate cancer is secondary to non-cell cycle-related
      mechanisms.

PMID- 11449446
TI  - An interactive internet-based intervention for women at risk of eating disorders:
      a pilot study.
AB  - OBJECTIVE: The Internet serves as a potentially effective method of treatment
      delivery through widespread education and interaction via synchronous Internet
      relay chat (IRC). The current study explores the feasibility of IRC in the
      delivery of an eating disorders prevention intervention. METHOD: This small pilot
      study describes the delivery of an efficacious eating disorder treatment using a
      novel medium. The on-line sessions are based on cognitive-behavioral treatment
      and are facilitated by a moderator. In addition to feasibility, preliminary
      evidence of acceptability and efficacy for an on-line intervention with college
      aged women is reported. RESULTS: Results indicate that IRC is an acceptable and
      feasible format for treatment delivery. In addition, descriptive and qualitative
      data suggest that this method of treatment delivery is potentially effective.
      DISCUSSION: This pilot study provides increased knowledge of the viability of
      treatment delivery over the Internet, specifically, a psychoeducational IRC for
      eating disorder prevention.

PMID- 11449447
TI  - Childhood trauma has dose-effect relationship with dropping out from
      psychotherapeutic treatment for bulimia nervosa: a replication.
AB  - OBJECTIVE: The primary goal of this study was to replicate the finding that
      experiences of childhood trauma have a dose-effect relationship with dropping out
      from psychotherapeutic treatment for bulimia nervosa. It also aimed to replicate
      logistic regression findings that parental break-up predicts dropping out.
      METHOD: The cohort consisted of 114 women consecutively presenting to an
      outpatient eating disorders clinic with bulimia nervosa or atypical bulimia
      nervosa. Data were gathered using a retrospective, case-note approach and were
      analysed using logistic regression (LR). A correlation technique was employed to
      assess the presence of a dose-effect relationship between experiences of trauma
      in childhood and dropping out. LR models were double cross-validated between this
      and an earlier cohort. RESULTS: The dose-effect relationship between experiences
      of childhood trauma and dropping out was confirmed. Witnessing parental break-up
      in childhood again predicted dropping out of treatment in adulthood. Cross
      validation of LR equations was unsuccessful. DISCUSSION: These results strongly
      suggest that experiences of childhood trauma have a dose-effect relationship with
      dropping out. Parental break-up is a stable predictor of dropping out. It is
      possible that these experiences influence attachment style, particularly the
      ability to make and maintain a trusting relationship with a psychotherapist.
      Clinical implications are discussed.

PMID- 11449448
TI  - The role of family of origin food-related experiences in bulimic symptomatology.
AB  - OBJECTIVE: With the goal of developing a model relating family of origin
      experiences to maladaptive cognitions to bulimic symptom formation, the authors
      developed a measure of family of origin food-related experiences called the
      Family History Inventory. METHOD: A number (N = 662) of sixth to eighth-grade
      adolescents completed the inventory, eating and dieting expectancy measures, and
      the Bulimia Test-Revised (BULIT-R). RESULTS: Fourteen scales were identified in
      the inventory. They emphasized family teasing about weight, negative maternal
      modeling regarding food, and family rules concerning eating. Eleven of the 14
      scales correlated with the BULIT-R. Two superordinate factors called Family
      Teasing and Negative Maternal Modeling summarized 8 of the 14 subscales.
      Statistical tests were consistent with the hypothesis that eating and dieting
      expectancies mediate the influence of Family Teasing and Negative Maternal
      Modeling on bulimic symptomatology. DISCUSSION: There was good evidence for the
      validity of the Family History Inventory. The theoretical implications of the
      mediation tests are discussed.

PMID- 11449449
TI  - Neuroticism and conscientiousness as predictors of emotional, external, and
      restrained eating behaviors.
AB  - OBJECTIVE: We investigated the extent to which different forms of eating behavior
      as assessed by the Dutch Eating Behaviour Questionnaire are related to facets of
      the Big Five personality domains. METHOD: Respondents were 167 psychology
      students (126 females and 41 males) who volunteered for the study. RESULTS: Body
      mass index (BMI) and gender had significant main effects on eating behaviors.
      These results were moderated by a significant BMI x Gender interaction on
      emotional eating. Eating behaviors were significantly related to the personality
      facets associated with Neuroticism and Conscientiousness. DISCUSSION: The results
      are discussed with reference to previous research on eating behaviors and the
      nature of Neuroticism and Conscientiousness.

PMID- 11449450
TI  - Season of birth in females with anorexia nervosa in Northeast Scotland.
AB  - OBJECTIVE: To determine whether patients with anorexia nervosa exhibit an
      abnormal pattern in their season of birth. METHOD: Case records of female
      patients presenting to secondary services in Northeast Scotland from 1965 to 1997
      who received a clinical diagnosis of anorexia nervosa were examined. The months
      of birth of the 446 anorexic patients with a confirmed diagnosis were compared
      with 5,766 female control subjects born locally in 1951, 1961, 1971, and 1981.
      RESULTS: Patients with anorexia nervosa had an excess of births in the first 6
      months of the year (p =.013). The greatest excess was from March to June.
      DISCUSSION: This provides further evidence that birth dates of anorexics peak in
      the late spring and early summer. There are parallels with the epidemiology of
      schizophrenia. The evidence suggests that a seasonally fluctuating factor, most
      plausibly an intrauterine effect of common infectious agents during the winter
      months, is of etiological significance.

PMID- 11449451
TI  - Norms, normality, and clinical significant change: implications for the
      evaluation of treatment outcomes for eating disorders.
AB  - OBJECTIVE: The implications of the use of national norms of the Eating Disorders
      Inventory (EDI) are investigated. METHOD: A German version of the EDI was
      administered to a representative national sample (n = 650), a repeatedly measured
      community sample (n = 207), and a national inpatient sample with primary
      diagnoses of anorexia or bulimia nervosa (n = 959). Resulting scale distributions
      were compared with those of North American samples of the handbook. RESULTS:
      Normal ranges on several scales markedly differed when German community norms
      were used. When estimates of rates of clinical significant changes were based on
      German norms instead of on North American norms, rates were markedly lower for
      scales measuring core diagnostic features (e.g., binging/purging, Drive for
      Thinness) and higher for those measuring correlates (e.g., Maturity Fears,
      Interpersonal Distrust). DISCUSSION: Neglecting differences in national norms can
      lead to substantial misinterpretation of empirical findings in the diagnosis of
      eating disorders and the evaluation of treatment outcome.

PMID- 11449452
TI  - Assessment of bulimia nervosa: a comparison of interview and self-report
      questionnaire methods.
AB  - OBJECTIVE: The main aim of this study was to assess the level of agreement
      between the Eating Disorders Examination (EDE) and its self-report version (EDE
      Q) on key items in a clinic sample of patients with bulimia nervosa. A second
      objective was to assess the concordance between self-reported and objective body
      weight in the sample. METHOD: Sixty females who met DSM-IV criteria for bulimia
      nervosa (purging type) participated. Fifty-seven of them completed both the EDE
      and the EDE-Q. Self-reported weight was obtained during a telephone screening
      interview. Objective weight was subsequently measured at an assessment about a
      week later. RESULTS: The EDE generated higher scores than the EDE-Q for the
      frequency of objective binge and vomiting episodes. The two methods produced
      equivalent results for subjective binge episodes, laxative and diuretic misuse,
      and concerns about shape and weight. The self-report method underestimated body
      weight. DISCUSSION: These findings suggest that some core features of eating
      disorders are more accurately assessed using the EDE interview.

PMID- 11449453
TI  - Binge eating disorder and night eating syndrome: psychological and behavioral
      characteristics.
AB  - OBJECTIVE: The present study was designed to examine the psychological and
      behavioral characteristics associated with both night eating syndrome (NES) and
      binge eating disorder (BED) in 42 males and 41 females who were enrolled in a
      university-based weight loss center. METHOD: Individuals were classified into one
      of four groups: NES only (N = 23), BED only (N = 13), both NES and BED (N = 13),
      or no diagnoses of an eating disorder (N = 34). Analyses of covariance (covarying
      for age and gender) were conducted to compare patients with BED and NES. RESULTS:
      NES patients scored lower on disinhibition than BED patients (p <.01). Also,
      individuals who met criteria for both disorders scored higher than NES only
      patients on state anxiety (p <.01), disinhibition (p =.08), and trait anxiety (p
      =.08). DISCUSSION: These results suggest that NES represents a subcategory among
      the obese, which also overlaps with binge eaters. In addition, anxiety
      distinguished individuals who met criteria for both disorders from patients who
      were diagnosed with either NES or BED.

PMID- 11449454
TI  - Early environmental influences on restrictive eating pathology among nonclinical
      females: the role of temperature at birth.
AB  - OBJECTIVE: In eating-disordered populations, restrictive pathologies are
      associated with a higher rate of births in the spring and early summer. The
      reasons for this relationship are not understood. The present study of a
      nonclinical group aimed to determine whether there is a link between being born
      in warmer months and the level of restrictive pathology in later years. METHODS:
      The participants (N = 117) were all young adult females who were conceived and
      born in England. Each completed the relevant scales of the Eating Disorders
      Inventory and provided demographic information. Temperature at birth was
      determined using national meteorological records. RESULTS: Restrictive attitudes
      were stronger among women born during the warmer part of the year (May-August),
      and those attitudes were dimensionally associated with temperature at birth. Body
      dissatisfaction showed some of the same relationships. Neither period of birth
      nor temperature at birth was related to bulimic attitudes or body mass index.
      CONCLUSIONS: Being born during warmer months is significantly associated with
      restrictive eating attitudes among nonclinical females, although the link is
      relatively weak. Potential causal mechanisms are outlined, but further research
      is needed to explain this link in clinical and nonclinical groups.

PMID- 11449455
TI  - An eating disorder curriculum for primary care providers.
AB  - OBJECTIVE: Primary care providers frequently lack adequate training in treating
      eating disorders. This study examined the effectiveness of an eating disorder
      curriculum designed to address the lack of knowledge among primary care
      providers. METHOD: Medical social workers completed four intensive training
      sessions, each lasting 75 min. Participants completed questionnaires assessing
      eating disorder knowledge, perceived ability to treat eating disorders, and
      practice behaviors, before and after training as well as at 6-month follow-up.
      RESULTS: The eating disorder curriculum resulted in a significant increase in
      eating disorder knowledge and a moderate improvement in practice behaviors such
      as screening new patients for an eating disorder. Training did not significantly
      change providers' perceived ability to intervene. DISCUSSION: The results of this
      pilot study suggest that brief intensive training can increase providers'
      knowledge and change their routine clinical practices, resulting in increased
      rates of detection and intervention in the primary care setting.

PMID- 11449456
TI  - Aspects of food refusal in the elderly: the "hunger strike".
AB  - OBJECTIVE: To present food refusal in old age as a means of attempting to control
      the outcome of intergenerational family conflicts. METHOD: Two cases are
      described. RESULTS: Food refusal does not necessarily arise in the context of a
      classical eating disorder but may represent a form of protest, or hunger strike.
      DISCUSSION: Food refusal is seen as distinct from a pure anorectic pattern of
      behavior. It may be a separate psychobehavioral entity in old age. Behavioral
      methods may help to encourage a resolution by setting clear limits and
      encouraging patients to share responsibility in decision making.

PMID- 11449457
TI  - Psychosocial variables associated with binge eating in obese males and females.
AB  - OBJECTIVE: This study tested a psychosocial model of binge eating symptoms in
      obese men and women. Predictor variables included depression, dietary restraint,
      self-esteem, weight cycling, history of teasing, body dissatisfaction, and
      neuroticism. METHOD: Participants (N = 808) completed a packet of self-report
      questionnaires. RESULTS: Weight cycling, teasing about weight and shape, body
      dissatisfaction, negative affect, and dietary restraint comprised the best
      fitting models (original and cross-validation) for binge eating in women and men.
      These variables explained 61-72% of the variance in symptoms of binge eating in
      the samples of men and 70% of the variance in the samples of women. Although the
      male and female models were mostly similar, notable differences between them were
      found. DISCUSSION: The variables that comprise these etiological models should be
      considered in the development of prevention programs for obese binge eaters.
      Longitudinal studies, however, are needed to examine these etiological paths and
      to test for causal relationships.

PMID- 11449458
TI  - Binge eating and other psychopathology in patients with type II diabetes
      mellitus.
AB  - OBJECTIVE: Type II diabetes mellitus (DM), a common disease with many potential
      complications, is strongly associated with obesity. Alterations in food
      consumption can dramatically alter glucose control in individuals with Type II
      DM. Binge eating disorder (BED) is also closely associated with obesity. The
      nature of the relationship, if any, between Type II DM and BED is unclear.
      METHODS: Forty-three individuals (23 females, 20 males) with Type II DM were
      assessed using the Structured Clinical Interview for DSM-IV (SCID-I), the Three
      Factor Eating Questionnaire (TFEQ), and the Impact of Weight Scale. The most
      recent hemoglobin A1c level was recorded. Height and weight were also measured.
      RESULTS: Eleven subjects (25.6%) were diagnosed with BED. Individuals with BED
      had higher body mass index (BMI) scores, higher TFEQ Disinhibition and Hunger
      scores, and higher scores on all Impact of Weight subscales (except eating)
      compared with those without BED. Glycosylated hemoglobin levels did not differ
      between the two groups (8.1% vs. 8.4%; p = 0.553). DISCUSSION: Rates of BED in
      subjects with Type II DM were substantial. Other types of psychopathology were
      also common. Although glycosylated hemoglobin levels were similar in patients
      with and without BED, the presence of BED was associated with greater obesity.
      Assessment for BED is an important aspect of the management of patients with Type
      II DM.

PMID- 11449459
TI  - Reversible tubular dysfunction that mimicked Fanconi's syndrome in a patient with
      anorexia nervosa.
AB  - Patients with anorexia nervosa exhibit acid-base and electrolyte disturbances.
      Hypophosphatemia is commonly found in these patients during nutritional recovery.
      However, marked, possibly, life-threatening hypophosphatemia associated with
      proximal tubular dysfunction has not been previously described. We report a case
      of anorexia nervosa complicated by a nonacidotic proximal tubulopathy, which was
      manifested by renal glycosuria, as well as inappropriate phosphaturia and
      uricosuria resulting in hypophosphatemia and hypouricemia.

PMID- 11449460
TI  - An adult with Prader-Willi syndrome and anorexia nervosa: a case report.
AB  - A 39-year-old man with Prader-Willi syndrome presents for evaluation of
      uncontrolled weight loss. Past history was significant for gastric bypass and
      prior episodes of intentional dieting. Family history was significant for an
      alcoholic father and two siblings with anorexia nervosa. The patient was
      unconcerned about his weight loss despite cachexia and did not want to stop
      dieting. This presentation of a restrictive eating pattern in a man with a
      syndrome usually associated with compulsive hyperphagia is the first known report

PMID- 11449461
TI  - Misoprostol and the politics of convenience.

PMID- 11449462
TI  - Effects of some lignans and neolignans on the development and excretion of
      Rhodnius prolixus.
AB  - The effects of six lignans and neolignans as inhibitors of ecdysis and on the
      water balance in fourth-instar larvae of Rhodnius prolixus were studied by oral,
      topical and continuous contact treatments. The main results may be summarised as
      follows: (i) burchellin, pinoresinol, sesamin, licarin A and nordihydroguaiaretic
      acid (NDGA) did not cause feeding inhibition at doses of 100 micrograms/ml blood;
      podophyllotoxin had no antifeedant effect but caused a high moulting inhibition
      and significant toxicity when applied either orally or topically; (ii) the
      highest ecdysis inhibitory effects were observed with pinoresinol and NDGA when
      applied orally at a dose of 100 micrograms/ml (58% and 50% of moulting
      inhibition, respectively); burchellin inhibited 30% of the moulting at this
      concentration; (iii) by topical treatment none of the compounds presented any
      influence on the moulting cycle; and (iv) podophyllotoxin and burchellin
      significantly reduced the excretion of the insect in 24 h; the other compounds
      had no effect on excretion. The implications of these findings in relation to the
      pertinent biological events in R. prolixus are discussed.

PMID- 11449463
TI  - A new triterpene from callus of Pterocarpus santalinus.
AB  - A new pentacyclic triterpene was isolated from the callus induced from the stem
      cuttings of Pterocarpus santalinus. Based on spectral methods, the structure of
      the new compound was elucidated as 3-ketooleanane (1).

PMID- 11449464
TI  - Effects of Isatis cappadocica on humoral immune responses.
AB  - The effects of a 20% ethanol extract of Isatis cappadocica on humoral immune
      responses in rabbits and mice were studied. After intraperitoneal injection of
      0.25 and 0.5 g/kg, a dose-dependent effect was observed. In particular, the dose
      of 0.25 g/kg suppressed the primary immune responses, while the dose of 0.5 g/kg
      stimulated the secondary immune responses.

PMID- 11449465
TI  - Valerenic acid derivatives and valepotriates among individuals, varieties and
      species of Valeriana.
AB  - To investigate the variations of active compounds between species, varieties and
      individuals of Valeriana cultivated under the same environmental condition, the
      contents of valerenic acid derivatives and valepotriates in rhizomes and roots of
      different plant material were analysed by a HPLC method. Different species or
      varieties of Valeriana yielded 11.65-0.15 mg/g of valerenic acid derivatives, and
      1.81-0.03 mg/g of valepotriates. The variation between individuals of one
      commercial cultivar of V. officinalis ranged from 12.34 to 3.01 mg/g of valerenic
      acid derivatives, and 3.67-0.92 mg/g of valepotriates. Individuals from self
      pollinated mother plants, normal or regenerated, showed a similar variation. The
      variation of micropropagated plants was much less than the seed propagated
      plants. The ratio of mean values between valerenic acid derivatives and
      valepotriates was similar in all groups (3 < ratio < 8) except one group of
      micropropagated plants (ratio > 20).

PMID- 11449466
TI  - Studies on preventive and curative effects of berberine on chemical-induced
      hepatotoxicity in rodents.
AB  - Berberis aristata is an edible plant employed in the South Asian Traditional
      Medicine, particularly its fruits being used as a tonic remedy for liver and
      heart. In this investigation, berberine, a known compound from this plant, was
      studied for its possible antihepatotoxic action in rats. Pretreatment of animals
      with berberine (4 mg/kg; orally twice daily for 2 days) prevented the
      acetaminophen- or CCl4-induced rise in serum levels of alkaline phosphatase (ALP)
      and aminotransaminases (AST and ALT), suggestive of hepatoprotection. Post
      treatment with three successive oral doses of berberine (4 mg/kg every 6 h)
      reduced the hepatic damage induced by acetaminophen, while CCl4-induced
      hepatotoxicity was not modified, suggesting a selective curative effect against
      acetaminophen. Pretreatment of animals with a single oral dose of berberine (4
      mg/kg) induced prolongation of the pentobarbital (60 mg/kg, i.p.)-induced
      sleeping time as well as increased strychnine (0.3 mg/kg; i.p.)-induced toxicity,
      suggestive of inhibitory effect on microsomal drug metabolizing enzymes,
      cytochrome P450s (CYPs).

PMID- 11449467
TI  - Stimulation of anthraquinone production in suspension cultures of Cassia
      acutifolia by salt stress.
AB  - Suspension cultures of Cassia acutifolia were established by transferring callus
      tissues derived from root, hypocotyl and cotyledon explants onto liquid MS-medium
      supplemented with 1.0 mg/l 2.4-D and 0.1 mg/l kinetin and containing increasing
      levels of NaCl. The stress induced by salt NaCl raised anthraquinone content and
      reduced growth of cultures. The levels of anthraquinones and their glycosides as
      sennosides showed distinct changes in cells and media as well as in the different
      cultures initiated from various explants. Furthermore, the salt stress tended to
      affect more drastically the productivity of anthraquinones in hypocotyl and
      cotyledon cell cultures than in root cultures.

PMID- 11449468
TI  - Efficacy of an indigenous formulation in patients with bleeding piles: a
      preliminary clinical study.
AB  - The results of the clinical assessment of a multiherbal indigenous formulation on
      22 patients with bleeding piles are reported.

PMID- 11449469
TI  - Quercetin triglycoside from Capparis spinosa.
AB  - In addition to rutin, quercetin 3-O-glucoside and quercetin 3-O-glucoside-7-O
      rhamnoside, the methanolic extract of the aerial parts of Capparis spinosa
      yielded the new flavonoid quercetin 3-O-[6'"-alpha-L-rhamnosyl-6"-beta-D
      glucosyl]-beta-D-glucoside (1).

PMID- 11449470
TI  - In vitro cell-toxicity of Peganum harmala alkaloids on cancerous cell-lines.
AB  - The alkaloidic fraction of the methanol extract of Peganum harmala seeds was
      tested in vitro on three tumoral cell-lines: UCP-Med and Med-mek carcinoma, and
      UCP-Med sarcoma. Proliferation was significantly reduced at all tested
      concentrations (20-120 micrograms/ml) during the first 24 h of contact. A cell
      lysis effect occurred after 24 h and increased thereafter to complete cell death
      within 48-72 h, depending on tested concentration.

PMID- 11449471
TI  - Protective effect of Hemidesmus indicus against rifampicin and isoniazid-induced
      hepatotoxicity in rats.
AB  - Oral treatment with the ethanol extract of Hemidesmus indicus roots (100 mg/kg,
      for 15 days) significantly prevented rifampicin and isoniazid-induced
      hepatotoxicity in rats.

PMID- 11449472
TI  - New sources and antifungal activity of sesquiterpene lactones.
AB  - In the search for new sources of sesquiterpene lactones, six Centaurea species
      have been analyzed. The activity against the fungus Cunninghamella echinulata of
      (+)-cnicin (1) and (+)-salonitenolide (2), isolated from the Centaurea plants, as
      well as that of (+)-costunolide (3), (-)-dehydrocostuslactone (4), (-)
      lychnopholide (5) and (-)-eremantholide C (6), has been evaluated. Compounds 3
      and 4 showed noticeable EC50 values, whilst more polar lactones were inactive.
      These results suggest that a relatively low polarity is one of the molecular
      requirements for the antifungal activity of sesquiterpene lactones.

PMID- 11449473
TI  - A preliminary study on the anti-inflammatory properties of Emilia sonchifolia
      leaf extracts.
AB  - The aqueous and methanolic extracts of Emilia sonchifolia leaves progressively
      reduced rat paw oedema induced by subplantar injection of albumin, the aqueous
      extract showing a more pronounced effect than the methanol extract.

PMID- 11449474
TI  - Antibacterial activity of the essential oil of Cymbopogon densiflorus.
AB  - The essential oil of Cymbopogon densiflorus showed a wide spectrum of activity
      against Gram-positive and Gram-negative bacteria.

PMID- 11449475
TI  - Antimicrobial activity of Evodia elleryana.
AB  - The methanol extracts of Evodia elleryana, leaves, stem wood, stem bark, root
      wood and root bark were partitioned (petrol, dichloromethane, ethyl acetate). All
      obtained fractions showed a broad spectrum of antibacterial activity, while none
      were active against tested moulds.

PMID- 11449476
TI  - Antimicrobial activity of Bridelia ferruginea fruit.
AB  - Bridelia ferruginea fruit 60% methanolic extract exhibited antimicrobial activity
      against seven out of eight bacterial isolates at a concentration of 20 mg/ml.

PMID- 11449477
TI  - In-vitro schizonticidal screening of Calotropis procera.
AB  - Following an ethnobotanical approach, the ethanol extracts of Calotropis procera
      leaves, stems, roots, flowers and buds have been screened in vitro for
      antimalarial activity against chloroquine (CQ)-sensitive and CQ-resistant
      Plasmodium falciparum strains.

PMID- 11449478
TI  - Aliphatics from Peristrophe bicalyculata.
AB  - The isolation and spectral data of the new 14-methyl-tritriacont-14-en-15-ol (1)
      and 35-hydroxynonatriacontanal (2) from the aerial parts of Peristrophe
      bicalyculata are reported.

PMID- 11449479
TI  - Constituents of Cassia auriculata.
AB  - The isolation and spectral data of di-(2-ethyl) hexyl phthalate (1) from Cassia
      auriculata leaves are reported.

PMID- 11449480
TI  - Phytochemical study of Salvia moorcroftiana.
AB  - Four known flavonoids were isolated from the aerial parts of Salvia
      moorcroftiana.

PMID- 11449481
TI  - Sesquiterpenoids and phenolics from Lactuca perennis.

PMID- 11449482
TI  - A novel flavone glycoside from the stem of Bauhinia purpurea.
AB  - A novel flavone glycoside, 5,6-dihydroxy-7-methoxyflavone 6-O-beta-D
      xylopyranoside (1) was isolated from the chloroform-soluble fraction of the
      ethanolic extract of Bauhinia purpurea stems.

PMID- 11449483
TI  - Secondary metabolites from Senecio minutus and Senecio boissieri: a new
      jacaranone derivative.
AB  - Jacaranone (1), the related new dimethoxy derivative 2, and known triterpenoids
      were isolated from the aerial parts of Senecio minutus. The aerial parts and the
      rhizomes of Senecio boissieri afforded the furanoeremophilanes 3 and 4 and known
      triterpenoids.

PMID- 11449484
TI  - Constituents of the flowers of Persea gratissima.
AB  - The flowers of Persea gratissima yielded an acylated flavonol 3-O-trans-p
      coumaroylkaempferol (1), in addition to quercetin 3-O-rhamnoside (2) and
      isorhamnetin 3-O-glucoside (3).

PMID- 11449485
TI  - Splitting and lumping in the nosology of XLMR.
AB  - Although it is assumed that genes that influence cognitive function are
      ubiquitous in the human genome, to date, more such genes have been found on the X
      chromosome than on any other comparable segment of the autosomes. This is in
      large measure because of the power of hemizygosity in exposing mutations of X
      linked genes in males. Clinical manifestations, mapping of gene loci by linkage
      analysis or chromosome rearrangements, and gene identification by positional
      cloning or mutational analysis of candidate genes have permitted extensive
      lumping and splitting within the large and heterogeneous category of X-linked
      mental retardation (XLMR). Approximately 130 XLMR syndromes have been identified,
      25 gene loci have been mapped and cloned, and 55 other loci have been mapped but
      not cloned. Well-recognized syndromes (e.g., Fragile X and Coffin-Lowry
      syndromes) and syndromes represented by only a single family (e.g., Arena and
      monoamine oxidase-A syndromes) are among these more or less well-defined
      entities. In addition, more than 75 families with nonsyndromal XLMR have been
      regionally mapped and 7 causative genes have been identified.

PMID- 11449486
TI  - FMRP detection assay for the diagnosis of the fragile X syndrome.
AB  - Fragile X syndrome is almost always caused by the absence or deficit of the FMR1
      protein (FMRP). Diagnostic methods include polymerase chain reaction and Southern
      blotting, which are performed on DNA isolated from peripheral leukocytes.
      Recently, different immunocytochemical tests have been described to identify
      patients with fragile X syndrome, based on the detection of FMRP in cells by a
      monoclonal antibody. This review aims to provide an update on the different
      antibody methods for prenatal and postnatal diagnosis of the fragile X syndrome.

PMID- 11449487
TI  - Premature ovarian failure in the fragile X syndrome.
AB  - The full mutation leading to the fragile X syndrome is a dynamic trinucleotide
      repeat located in the 5' untranslated region of the FMR1 gene. The premutation
      allele contains approximately 60 to 199 repeats, is unstable, and originally not
      considered detrimental; that is, there did not appear to be a phenotype
      consequence of the long repeat tract. However, in the late 1980s and early 1990s,
      preliminary findings suggested that nonimpaired heterozygotes were at risk of
      early menopause and increased rates of twinning, both indications of ovarian
      failure. Once premutation carriers could be distinguished from full mutation
      carriers, this phenotype was found to be restricted to premutation carriers only.
      Based on the recent studies reviewed here, approximately 21% of premutation
      carriers have premature ovarian failure (POF) compared to only 1% in the general
      population, or a relative risk of 21. Moreover, among women with idiopathic
      sporadic or the more rare form of familial POF, approximately 2% and 14%,
      respectively, carry the premutation. To date, data supporting increased twinning
      rates are conflicting and need to be resolved. Neither the underlying cellular
      pathophysiology of POF caused by the premutation allele nor molecular mechanism
      underlying the presence of the long repeat tract of the premutation allele is
      understood. Irrespective, women who carry the premutation allele should have not
      only genetic counseling but also fertility counseling to ensure that they reach
      their goals for reproduction.

PMID- 11449488
TI  - Transcription of the FMR1 gene in individuals with fragile X syndrome.
AB  - Fragile X syndrome generally arises as a consequence of a large expansion of a
      CGG trinucleotide repeat element that is located in the GC-rich promoter region
      of the fragile X mental retardation gene (FMR1). In the conventional model for
      fragile X, clinical involvement arises as a consequence of silencing of the FMR1
      gene, with the attendant loss of FMR1 protein (FMRP). However, it has recently
      been demonstrated that most males with large premutation alleles (100-200
      repeats), or with unmethylated full mutation alleles, have FMR1 mRNA levels that
      are higher than normal, despite reduced levels of FMRP. In the current work, we
      extend and confirm these observations using quantitative (fluorescent) reverse
      transcription polymerase chain reaction on larger sample populations,
      establishing that even for smaller premutation alleles (55-100 repeats) the mRNA
      levels are significantly elevated (mean 2.1-fold elevation; P = 3.9 x 10(-3)),
      relative to normal controls. Thus, an abnormal molecular phenotype is established
      close to the upper end of the normal range. We also demonstrate that the levels
      of FMR1 mRNA are elevated in females with premutation alleles; however, the mRNA
      levels are more varied than in the males, and are attenuated in a manner that is
      consistent with the fraction of normal alleles that are active in any given
      individual. Finally, we demonstrate that in lymphoblastoid cells derived from a
      patient with a severe form of fragile X caused by a point mutation in the second
      KH domain of the gene, but with a normal CGG element (25 repeats), the FMR1 mRNA
      level is normal. Thus, although models in which FMRP level (or level of function)
      modulates transcriptional activity remain viable, other explanations for the
      elevated message levels, including direct (cis) effects of the CGG element on
      transcription, must also be considered.

PMID- 11449489
TI  - Molecular-clinical spectrum of the ATR-X syndrome.
AB  - Since the identification of the ATRX gene (synonyms XNP, XH2) in 1995, it has
      been shown to be the disease gene for numerous forms of syndromal X-linked mental
      retardation [X-linked alpha thalassemia/mental retardation (ATR-X) syndrome,
      Carpenter syndrome, Juberg-Marsidi syndrome, Smith-Fineman-Myers syndrome, X
      linked mental retardation with spastic paraplegia]. An attempt is made in this
      article to review the clinical spectrum associated with ATRX mutations and to
      analyse the evidence for any genotype/phenotype correlation.

PMID- 11449490
TI  - X-linked malformations of cortical development.
AB  - Disorders of the development of the human cortex are recognized as significant
      causes of mental retardation, epilepsy, and congenital neurologic deficits. These
      malformations may be restricted to the brain or may be one component of a
      generalized malformation syndrome. Through the efforts of several groups, a large
      number of human cortical malformations have been identified and classified.
      Studies of informative families and sporadic patients with specific chromosomal
      rearrangements or deletions have demonstrated a genetic basis for many of these
      disorders. Subsequent work has facilitated a precise genetic diagnosis and
      provided insight into the molecular basis of some of these malformations. This
      review will discuss four cortical malformation syndromes, which are known or
      likely to have an X-linked inheritance pattern: bilateral periventricular nodular
      heterotopia, X-linked lissencephaly/subcortical band heterotopia, X-linked
      lissencephaly with abnormal genitalia, and X-linked bilateral perisylvian
      polymicrogyria.

PMID- 11449491
TI  - In search of the MRX genes.
AB  - Mental retardation (MR) is one of the most common human disorders. MR may be just
      one of the clinical signs of a complex syndrome or it may be associated with
      metabolic disorders or with disorders of brain development, but in many patients
      [nonspecific MR (NSMR)], it is the only consistent clinical manifestation. It is
      expected that NSMR is caused by alterations in molecular pathways important for
      cognitive functions. Insights into NSMR have recently come from the study of X
      linked MR as eight genes were identified during the last few years. This
      development has represented a fundamental breakthrough in our understanding of
      NSMR and of cognitive functions and has opened new perspectives in the study of
      MR. The new genes identified are a heterogeneous group, but it is very intriguing
      that they are all directly or indirectly involved in signaling pathways and that
      the majority are proteins that regulate members of the Ras superfamily of small
      GTP binding proteins.

PMID- 11449492
TI  - Sixty years of X-linked mental retardation: a historical footnote.
AB  - X-linked mental retardation (XLMR) is a most exciting field of modern medical
      genetics. It made spectacular advances over the last twenty years, after the
      advent of molecular genetics. The discovery of the FMR1 gene unraveled the cause
      of the most common form of heritable mental retardation and provided the
      prototype of dynamic mutations. New genes continue to be mapped to the X
      chromosome and more and more are being cloned and characterized, clarifying the
      nosology of XLMR and, more importantly, adding to our understanding of the
      mechanisms of intellectual development, normal and abnormal. Looking back to a
      more or less recent past may provide clues for future discoveries.

PMID- 11449493
TI  - Lantana camara L. (Verbenaceae).
AB  - Lantana camara L. is regarded both as a notorious weed and a popular ornamental
      garden plant and has found various uses in folk medicine in many parts of the
      world. Some taxa of the widely variable L. camara complex are toxic to small
      ruminants and this effect has been associated with the types and relative amounts
      of some triterpene ester metabolites. However, L. camara also produces a number
      of metabolites in good yields and some have been shown to possess useful
      biological activities. All these aspects are considered in this review to allow
      an evaluation of the potential for utilisation of the large biomass of Lantana
      available. The phytochemistry of other members of the Lantana genus is included.

PMID- 11449494
TI  - Levels of lantadenes, bioactive pentacyclic triterpenoids, in young and mature
      leaves of Lantana camara var. aculeata.
AB  - Levels of the lantadene pentacyclic triterpenes were quantified in young and
      mature leaf samples of Lantana camara var. aculeata, by HPLC. The amount of
      different lantadenes (mg/100 g dry wt.) in young and mature leaf samples,
      respectively, was: lantadene A, 491.5 +/- 6.3, 805.9 +/- 52.8; lantadene B, 347.0
      +/- 3.0, 522.3 +/- 37.1; lantadene C, 191.3 +/- 10.3, 424.8 +/- 39.1; lantadene
      D, 49.7 +/- 5.3, 177.4 +/- 19.0; reduced lantadene A, 19.1 +/- 2.3, 28.7 +/- 4.5;
      reduced lantadene B, 13.0 +/- 1.3, 18.6 +/- 1.2; and 22 beta-hydroxyoleanonic
      acid, 82.5 +/- 11.4, 167.7 +/- 30.1.

PMID- 11449495
TI  - Limonoids and phytol derivatives from Cedrela sinensis.
AB  - Two new compounds, cedrellin (1) and 2,6,10,15-phytatetraene-14-ol (2), together
      with five known compounds, 7 alpha-obacunyl acetate, 6-acetoxyobacunol acetate, 7
      alpha-acetoxydihydronomilin, 2,6,10-phytatriene-1,14,15-triol and phytol were
      isolated from leaves of Cedrela sinensis. Their structures were elucidated on the
      basis of combined one- and two-dimensional spectral techniques.

PMID- 11449496
TI  - A new cytotoxic naphthopyrone dimer from Paepalanthus bromelioides.
AB  - A new naphthopyrone dimer was isolated from the capitula of Paepalanthus
      bromelioides by chromatographic procedures. It structure was deduced from
      spectrometric data. On colorimetric assay for cytotoxicity the new dimer showed
      IC50 of 55.9 microM.

PMID- 11449497
TI  - Factors affecting volatile terpene and non-terpene biotransformation products in
      plant cell cultures.
AB  - Suspension cultures from Peganum harmala were shown to carry out
      biotransformations of a number of terpenes and non-terpenes. The rate of
      biotransformation was dependent upon substrate concentration, density of cell
      suspensions, and the structure and isomeric form of the substrates.

PMID- 11449498
TI  - A new prenylated flavanone from the roots of Sophora flavescens.
AB  - A new prenylated flavanone was isolated from the roots of Sophora flavescens. The
      structure of the new compound was elucidated as (2S)-7,4'-dihydroxy-5-methoxy-8
      (gamma,gamma-dimethylallyl)-flavanone (1) on the basis of chemical and spectral
      evidence.

PMID- 11449499
TI  - Immunologically active polysaccharides from Centrosema pubescens.
AB  - Two polysaccharides with mean M(r)s of 2.0 x 10(6) and 3.75 x 10(5), were
      isolated from powdered seeds of Centrosema pubescens by fractionation on
      Sephacryl S-300 HR. Chemical and spectroscopic studies indicated that they have a
      backbone chain composed of beta-(1-->4)-linked D-galactopyranose residues having
      branches composed of alpha-(1-->5)-linked L-arabinofuranose residues at position
      6 of D-galactose of the backbone chain. The polysaccharides showed
      reticuloendothelial system-potentiating activity in a carbon clearance test.

PMID- 11449500
TI  - Antihyperglycemic activity of Euphrasia officinale leaves.
AB  - The effects of the aqueous extract of the leaf of Euphrasia officinale on blood
      glucose levels in normal and alloxan-diabetic rats were investigated. The
      treatment of alloxan-induced diabetic rats brought down the raised glucose
      levels, while the extract was devoid of hypoglycemic effect in normal rats.

PMID- 11449501
TI  - Fungitoxic alkaloids from Hokkaido Papaveraceae.
AB  - Papaver orientale, Dicentra spectabilis and Chelidonium majus, three Papaveraceae
      collected from Hokkaido area, were studied for their fungitoxic alkaloids. Ten
      alkaloids were isolated, identified and tested for their fungitoxic activity. Two
      of these isolates were found to be new compounds.

PMID- 11449502
TI  - Control of urinary risk factors of stones by betulin and lupeol in experimental
      hyperoxaluria.
AB  - Urolithiasis, the process of formation of stones in the kidney and the urinary
      tract, is the major clinical manifestation of hyperoxaluria. Crystal deposition,
      as indicated by increased stone-forming constituents in urine, such as calcium,
      oxalate and uric acid, and decreased concentration of inhibitors, such as
      magnesium and glycosaminoglycans, was observed in pyridoxine-deficient
      hyperoxaluric rats. Renal tubular damage was indicated by increased excretion of
      enzymes such as alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl
      transferase, beta-glucuronidase and N-acetyl glucosaminidase. Fibrinolytic
      activity was found to be reduced. Administration of pentacyclic triterpenes such
      as lupeol and its structural analogue betulin to hyperoxaluric rats minimised the
      tubular damage and reduced the markers of crystal deposition in the kidneys. In
      this connection, lupeol was found to be more effective than betulin.

PMID- 11449503
TI  - Antibacterial and molluscicidal activities of the essential oil of Chrysanthemum
      viscidehirtum.
AB  - The volatile fraction of Chrysanthemum viscidehirtum aerial parts, consisting
      mainly of limonene, beta-farnesene and many oxygenated sesquiterpenes, was
      screened for activity against 21 microbial strains. This essential oil exhibited
      activity against all germs tested, in particular Salmonella typhi and Proteus
      mirabilis. It also showed molluscicidal activity against Bulinus truncatus.

PMID- 11449504
TI  - Evaluation of antitumor activity of some medicinal plants of Bangladesh by potato
      disk bioassay.
AB  - The antitumor activity of the ethanolic extracts of 12 medicinal plants of
      Bangladesh, including the vincristine-vinblastine producing Catharanthus roseus
      was studied using the potato disk bioassay technique. Among these, 10 plant
      extracts at 25.0-microgram/disc exhibited significant inhibition of crown gall
      tumors caused by Agrobacterium tumefaciens.

PMID- 11449505
TI  - Effect of Feronia limonia on mosquito larvae.
AB  - Bioassay guided fractionation of the acetone extract of Feronia limonia dried
      leaves afforded a potent mosquito larvicide, identified as n-hexadecanoic acid
      and found to be effective against fourth instar larvae of Culex quinquefasciatus,
      Anopheles stephensi and Aedes aegypti, with LC50 of 129.24, 79.58 and 57.23 ppm,
      respectively.

PMID- 11449506
TI  - Anti-inflammatory activity of Pothomorphe peltata leaf methanol extract.
AB  - The methanol extract of Pothomorphe peltata leaves, orally administered at the
      dose of 20 mg/kg (equivalent to 2.50 g dry plant/kg) body weight, exhibited a
      significant anti-inflammatory activity, comparable with phenylbutazone (80 mg/kg,
      p.o.), against adjuvant-carrageenan-induced edema in rats.

PMID- 11449507
TI  - Antibacterial activity and cytotoxicity of Miliusa velutina.
AB  - Goniothalamusin and two mixtures, acetogenins-A and acetogenins-B, isolated from
      a petroleum ether extract of the stem bark of Miliusa velutina exhibited
      significant antibacterial and cytotoxic activities.

PMID- 11449508
TI  - Antinociceptive activity of Euphorbia heterophylla roots.
AB  - Following an identified use of the plant as analgesic in traditional medicine,
      the hexane, chloroform and ethyl acetate extracts of Euphorbia heterophylla root
      have been tested for antinociceptive activity in rats. All extracts showed
      significant effects at doses of 150-300 mg/kg i.p.

PMID- 11449509
TI  - Anti-inflammatory activity of (+)-usnic acid.
AB  - (+)-Usnic acid, isolated from the lichen Roccella montagnei, showed a dose
      dependent anti-inflammatory activity when tested on rats, employing acute and
      chronic models.

PMID- 11449510
TI  - Antifungal properties of Ocimum gratissimum essential oil (ethyl cinnamate
      chemotype).
AB  - Largely widespread in tropical countries, Ocimum gratissimum has been claimed for
      many uses in folk medicine. Recent research on its essential oils showed five
      chemotypes. An Indian chemotype, with a high level of ethyl cinnamate, presents,
      in vitro, an interesting spectrum of antifungal properties.

PMID- 11449511
TI  - Antimicrobial activity of Fabaceae species used in Yucatan traditional medicine.
AB  - The methanol and water extracts of six Fabaceae species, traditionally used in
      Mayan medicine for the treatment of diarrhoea and eye infections, were
      phytochemically screened and tested for in vitro antimicrobial activity. Four
      species showed activity against Gram positive bacteria, five exhibited some
      activity against Candida albicans, two exhibited activity against Aspergillus
      niger and only one, Mimosa pigra, inhibited growth of Pseudomonas aeruginosa.
      None of the extracts was active against Escherichia coli.

PMID- 11449512
TI  - HIV-inhibitory diterpenoid from Anisomeles indica.
AB  - The 1H- and 13C-NMR spectral data of ovatodiolide (1), a diterpenoid from
      Anisomeles indica, and its anti-HIV activity are reported.

PMID- 11449513
TI  - Antitumor activity of epifriedelanol from Vitis trifolia.
AB  - The isolation and NMR spectral data of epifriedelanol from Vitis trifolia are
      reported. It demonstrated antitumor activity in a potato disc bioassay.

PMID- 11449514
TI  - Constituents of Cassia laevigata.
AB  - Calendin (1), cinnamic acid (2), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1
      one (3), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (4), 3-hydroxy
      1-(4-hydroxy-3,5-dimethoxyphenyl)-propan-1-one (5), syringic acid (6) and
      vanillic acid (7) have been isolated from a dichloromethane extract of the leaves
      and branches of Cassia laevigata.

PMID- 11449515
TI  - Hancokinol from Vincetoxicum officinale.
AB  - Hancokinol (1), a member of migrated lupane triterpenoids, was isolated from the
      aerial parts of Vincetoxicum officinale, along with known plant sterols and long
      chain alkanols.

PMID- 11449516
TI  - Major dicaffeoylquinic acids from Artemisia vulgaris.
AB  - The two major caffeoylquinic acids, 3,5-di-O-caffeoylquinic acid and 1,5-di-O
      caffeoylquinic acid, were new-isolated from the flowering tops of Artemisia
      vulgaris (yield 2.0% and 0.3% on dry weight, respectively) and characterized by
      spectroscopic analysis.

PMID- 11449517
TI  - A new germacranolide from Artemisia pallens.
AB  - A new germacranolide has been isolated from the aerial parts of Artemisia pallens
      and the structure was established as 4,5 beta-epoxy-10 beta-hydroxy-1-en-3-one
      trans-germacran-6 alpha,12-olide (1) by comparison with its 10 alpha-epimer
      isolated from the same plant.

PMID- 11449518
TI  - Constituents of Eulophia petersii.
AB  - The isolation of five known phenanthrenes and a mixture phytosterols from roots
      of Eulophia petersii is reported.

PMID- 11449519
TI  - Pyranoisoflavones from Rinorea welwitschii.
AB  - Reversed-phase HPLC analysis of a dichloromethane extract of the stem-barks of
      Rinorea welwitschii has afforded two pyranoisoflavones, alpinumisoflavone (1) and
      di-O-methylalpinumisoflavone (2).

PMID- 11449520
TI  - Jusmicranthin, a new arylnaphthalide lignan from Justicia neesii.
AB  - The isolation of jusmicranthin (1), a novel lignan from Justicia neesii, is
      reported. Compound 1 represents a new class of angularly fused arylnaphthalides
      having a gamma-hydroxylactone unit.

PMID- 11449521
TI  - Arctiin and onopordopicrin from Carduus micropterus ssp. perspinosus.
AB  - The isolation of (-)-arctiin (1), arctigenin (2), onopordopicrin (3),
      kaempferide, eriodictyol, luteolin and stigmasterol from the aerial parts of
      Carduus micropterus ssp. perspinosus, is reported.

PMID- 11449522
TI  - The major flavonoid of Dodonaea angustifolia.
AB  - The major leaf flavonoid of Dodonaea angustifolia, an important South African
      traditional medicine, has been identified as 5,7,4'-trihydroxy-3,6
      dimethoxyflavone (1).

PMID- 11449523
TI  - Novel quinoline alkaloid from trunk bark of Galipea officinalis.
AB  - The isolation of N-methyl-4-hydroxy-3-(2',3'-epoxyisobutyl)-2-quinolone (1), a
      new natural compound, and candicine (2) from Galipea officinalis trunk bark is
      reported. This is the first report of candicine in the genus Galipea.

PMID- 11449524
TI  - Two novel xanthones from Garcinia mangostana.
AB  - The isolation of two novel xanthones isolated from the fruit hulls of Garcinia
      mangostana is reported. The structures were elucidated by means of spectroscopic
      analysis.

PMID- 11449525
TI  - Condensed tannins from Myrica gale.
AB  - From the aerial parts of the Myrica gale catechin, epicatechin, gallocatechin,
      epigallocatechin, epigallocatechin-3-O-gallate, gallocatechin-(4 alpha-8)
      epicatechin, gallocatechin-(4 alpha-8)-epigallocatechin, and gallocatechin-(4
      alpha-8)-gallocatechin-(4 alpha-8)-gallocatechin (1), were isolated. The 1H- and
      13C-NMR data of the peracetate derivative of the trimer are reported.

PMID- 11449526
TI  - Constituents of Brosimum potabile.
AB  - The ethanolic extract from the stem of Brosimum potabile afforded (-)-centrolobin
      (1), isolated for the first time in this genus. The identification of this
      compound included COSY and NOESY two-dimensional NMR data.

PMID- 11449527
TI  - Monoterpenoids from the seeds of Heracleum candolleanum.
AB  - The isolation and NMR spectra of 2-exo,3-endo-camphanediol (1) and 2-pinene-4,10
      diol (2) from the seeds of Heracleum candolleanum are reported.

PMID- 11449528
TI  - Pyrrolizidine alkaloids from Senecio lorenthii.
AB  - The isolation and NMR spectra of otosenine (1) and seneciphylline (2) from
      Senecio lorenthii are reported.

PMID- 11449529
TI  - Perspectives in allergology. Science and profession.

PMID- 11449530
TI  - Serum potassium levels, CPK-MB and ECG in children suffering asthma treated with
      beclomethasone or beclomethasone-salmeterol.
AB  - Asthma morbidity and mortality has increased. One of the possible causes is the
      excessive use of beta agonists. The aim of this study is to compare the effects
      of six week treatment with beclomethasone alone (Ibec) or the combination of
      beclomethasone-salmeterol (Ibe + Isal) on serum potassium (K), CPK-MB and ECG in
      children suffering asthma. It was a prospective, randomised, open cross-over
      trial. Patients received either Ib2 (2 puff/12 hr, 100 micrograms per puff) or
      Ibe + Isal (B 2 puff/12 hr, 100 micrograms per puff and S 2 puff/12 hr, 25
      micrograms per puff) with dose meter inhaler by 6 weeks, with a four-week wash
      out period between the treatments. K, CPK-MB and ECG were assessed at baseline,
      and after each treatment period. There were 9 girls and 20 boys, aged 11 +/- 2.18
      (mean +/- SD) years, baseline K was 4.57 +/- 0.43 mEq/l, after B K 4.38 +/- 0.39
      IU and after BS K 4.38 +/- 0.40. The CPK-MB level were baseline 14.75 +/- 4.5,
      after B 20.10 +/- 6.9 and after BS 21 +/- 8.05 (p < 0.05). Baseline QTc was 0.416
      +/- 0.02 msec, after B 0.425 +/- 0.027, and after BS 0.415 +/- 0.029. We conclude
      that the treatment of children with asthma with 400 micrograms per day of Ibec or
      concomitantly with 100 micrograms of Isal for 6 weeks does not alter the serum K+
      or the QTc. However, the CPK-MB has a significant increment with both treatments
      but without clinical and/or ECG changes. We can't affirm that Ibec or Ibec plus
      Isal have a cardiotoxic side-effect by the only presence of high levels of CPK
      MB. We agree that it is necessary a close follow up of these apparently
      asymptomatic patients not induce important cardiovascular changes although CPK-MB
      was increased.

PMID- 11449531
TI  - Fluticasone propionate and budesonide do not influence bone metabolism in the
      long term treatment of asthma.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are recommended in the treatment of
      asthmatic patients. They have been said to be efficacious in the treatment of
      asthma in respect to cortisol and bone metabolism. METHODS: The effects of the
      two inhaled corticosteroid, budesonide (BUD) and fluticasone propionate (FP) on
      bone metabolism, morning cortisol and their effects on the clinical parameters
      (FEV1, diurnal variation of peak expiratory flow rate = PEFR and log PC20) were
      examined in a group of 16 asthmatic patients. Eight patients used 800
      micrograms/daily BUD and 8,400 micrograms/daily FP during 6 months period.
      RESULTS: Both BUD and FP improved clinical parameters as determined by FEV1 (p <
      0.05) and PEFR (p < 0.01). There was no difference in respect to log PC20 values
      in either group (p > 0.05). Both treatments didn't change morning cortisol (p <
      0.05). Both FP and BUD didn't change any indices of bone formation as determined
      by serum alkaline phosphatase, bone alkaline phosphatase, osteocalcin and
      carboxyterminal propeptide of type 1 procollagen and bone resorption as
      determined by urinary calcium and deoxypyridinoline (p > 0.05). In addition there
      was no significant effect on calcium and phosphate metabolism (serum calcium,
      phosphate and parathyroid hormone). CONCLUSION: As a result, having no adverse
      effect on bone metabolism and adrenal function, in the regard to clinical
      efficacy, FP is as effective as the double dose of BUD on PEFR and FEV1.

PMID- 11449532
TI  - Pneumomediastinum and pneumopericardium: unusual and rare complications of asthma
      in a 4 years old girl.
AB  - We describe a 4-year-old girl with asthma who presented with pneumomediastinum,
      pneumopericardium and subcutaneous emphysema. She was admitted to our hospital
      with dyspnea, chest pain, palpitation and cough of two days duration. She had
      attacks of cough, dyspnea and wheezing from two years of age, but she did not
      have a diagnosis of asthma previously. She was dyspneic and had subcutaneous
      emphysema in the neck, axilla and thorax. In the skin prick test (Center Lab.
      USA) she had positive reaction to Dermatophagoides pteronyssinus,
      Dermatophagoides farinae, mold mix, tree mix and grass mix. Pulmonary function
      tests could not be performed. In the chest X-ray air was seen in mediastinum and
      subcutaneous area and the epicardium was surrounded completely with air. She was
      treated successfully with inhaled salbutamol and budesonide. Radiological signs
      of pneumopericardium and pneumomediastinum disappeared completely in ten days
      period. In the light of this case we want to mention that early diagnosis and
      treatment of asthma should be done to prevent serious complication of asthma.

PMID- 11449533
TI  - Immediate reaction to clarithromycin.
AB  - We present the case of bronchospastic reaction to clarithromycin had during a
      drug challenge test. Personal allergic history was negative for respiratory
      allergies and positive for adverse drug reactions to general and regional
      anesthesia and to ceftriaxone. After the administration of 1/4 of therapeutic
      dose of clarithromycin the patient showed dyspnea, cough and bronchospasm in all
      the lung fields. The positivity of the test was confirmed by the negativity to
      the administration of placebo. The quickness and the clinical characteristic of
      the adverse reaction suggest a pathogenic mechanism of immediate-type
      hypersensitivity. On reviewing the literature we have found no reports of
      bronchospastic reaction to clarithromycin. Macrolides are a class of antibiotics
      mainly used in the last years in place of beta-lactams because of a broad
      spectrum of action and a low allergic power. In fact, there are few reports on
      allergic reactions to these molecules. Clarithromycin is one of the latest
      macrolides, characterised by the presence of a 14-carbon-atom lactone ring as
      erythromycin, active on a wide spectrum of pathogens.

PMID- 11449534
TI  - Syndrome auriculotemporal.
AB  - Two cases of auriculotemporal syndrome are presented in two male children that
      began in the first years of life to present reactions of linear erythema
      itinerary on the cheeks after eating several foods. The allergologic study with
      these foods was negative, reproducing the clinical picture after their ingestion.

PMID- 11449535
TI  - Specific immune response to Phleum pratense plant profilin in atopic patients and
      control subjects.
AB  - BACKGROUND: Phleum pratense (Phl p) pollen is a known cause of allergic disease
      worldwide. Profilins have been identified as functional plant pan-allergens. The
      role of Phl p profilin in the specific immune response in sensitized Phl p
      patients is unknown. METHODS: Skin prick test and specific serum IgE levels were
      performed in 26 patients allergic to Phl p and in 18 nonallergic control donors.
      Peripheral blood mononuclear cells were isolated from both groups and stimulated
      with crude extract or highly purified Phl p profilin, and the production of type
      I and type II cytokines was determined in patients and controls stimulated with
      specific and polyclonal stimulus. T-cell lines specific to Phl p profilin were
      established from PBMCs and cross-reactivity with another highly purified profilin
      from Parietaria judaica (Pj) was evaluated. RESULTS: Patients allergic to Phl p
      profilin showed increased T-cell-proliferative responses to this profilin
      compared with control subjects. The production of IL-4 and IFN-gamma in response
      to the specific stimulus was undetectable. However, the production of IL-4 and
      IFN-gamma in response to a polyclonal stimulus (PHA) was measurable and different
      for atopic patients and control subjects: IL-4 was higher (p < 0.001) in allergic
      patients and IFN-gamma lower (although not significant) in controls. Neither the
      T-cell responses nor the production of IL-4 in response to a polyclonal stimulus
      (PHA) correlated with the individual degree of cutaneous response to Phl p
      profilin or to the levels of specific Phl p IgE. The T-cell lines tested did not
      show any cross-reactivity with Pj profilin. CONCLUSIONS: Phl p profilin is in
      part responsible for the T-cell mediated immunological response in patients
      allergic to Phl p. The response is very specific since Phl p profilin specific T
      cell lines did not show cross-reactivity with a highly homologous profilin from
      Parietaria judaica (Pj). The lack of correlation between the proliferative T-cell
      response and polyclonal IL-4 production with allergen-specific serum IgE and SPT
      probably indicates that some of the responding T-cells may be involved in immune
      reactions other than the support of IgE production.

PMID- 11449536
TI  - [Nonequilibrium state of electrochemically activated water and its biological
      activity].
AB  - Changes in the physicochemical parameters (pH, redox potential and
      electroconductivity) of catholyte and anolyte produced by membrane electrolysis
      of distilled water and dilute (c < 10(-3) M) sodium chloride solutions were
      studied. The relaxation of these parameters after electrolysis and the influence
      of catholyte and anolyte on the growth of roots of Tradescantia viridis grafts,
      the development of duckweed, and the motive activity of infusoria Spirostomum
      ambiguum were investigated. It was found that the anolyte of distilled water
      stimulated development of these biological objects. The direction of shift of
      physicochemical parameters of catholyte and anolyte from equilibrium values and
      the type of their biological activity (stimulation or inhibition) depend on salt
      concentration in initial solution. Barbotage of initial distilled water with
      argon or nitrogen leads to a greater decrease in the redox potential of catholyte
      during electrolysis. The physicochemical parameters relax to equilibrium values,
      and the biological activity of catholite and anolyte decreases with time and
      practically disappears by the end of the day. It was found that the oxidation of
      reducing agent by atmospheric oxygen is not the sole cause of the relaxation of
      catalyte redox potential. The increase in the ionic strength of catholite and
      anolyte by the addition of concentrated sodium chloride after electrolysis
      decreases the rate of redox potential relaxation several times. The redox
      potential can be maintained for long periods by freezing.

PMID- 11449537
TI  - [Absorption of infrared radiation by a thin water layer].
AB  - The unhomogeneous distribution of infrared absorption in a thin water layer and
      its time instability were explained. The parameters of interribbon interaction in
      the case of thin water layers with bound influence were evaluated.

PMID- 11449538
TI  - [Low-frequency vibrations of a Mg pyropheophorbide-histidine complex].
AB  - The spectrum of vibrations and normal model for the Mg piropheophorbide-histidine
      complex was calculated using the MNDO-PM3 (MOPAC) semiempirical quantum chemical
      method. The delocalization index and the distribution function were introduced to
      describe the shape of normal vibrations. The greatest part (approximately 65%) of
      the low-frequency vibrations (1-400 cm-1) was shown to delocalize over both the
      His and Mg piropheophorbide molecules. Leu, Met, and Asp were also studied as the
      fifth ligand to the Mg piropheophorbide molecule. It is concluded that the fifth
      amino acid ligand to porphyrin molecules causes marked geometrical distortions in
      porphyrin, and induces a new, compared to four coordinated pigment, spectrum of
      normal modes.

PMID- 11449539
TI  - [Catalytic effect of ferricyanide on the rate of electron transfer between
      myoglobin and cytochrome c].
AB  - The influence of small amounts of low-molecular electron acceptor, potassium
      ferricyanide, 1 to 20% relative to the cytohrome c concentration, on the rate of
      electron transfer in the sperm whale oxymyoglobin--horse heart cytochrome c and
      deoxymyoglobin--cytochrome c systems (under aerobic and anaerobic conditions,
      respectively) was studied. At low ionic strength, the redox reaction rate was
      found to increase proportionally to the concentration of ferricyanide in both
      redox systems. The effect depends on pH in the pH range 5-8, increasing sharply
      at pH < 6. It was shown that the enhancing of electron transfer is caused by the
      complexing of [Fe(CN)6]3- with cytohrome c in the Lys72 region, where one of the
      two strong binding sites for this anion is determined by NMR. Both the high ionic
      strength and the chemical modification of Lys72 residue inhibit this effect at
      low ionic strength, markedly decreasing the rate of reaction with myoglobin.
      Under the same conditions, the effect of ferricyanide in the reaction of oxy-Mb
      with yeast cytohrome c, which is isopotential to animal cytochromes c but
      possesses trimethylated Lys72, was several times smaller. In turn, the chemical
      modification of His residues in myoglobin and the complexing of zinc ion to
      His119(GH1) almost completely inhibit electron transfer in the systems. Thus,
      electron transfer between the proteins must proceed through the formation of the
      Mb.[Fe(CN)6]3-.Cyt c ternary complex, the contacting sites being localized in the
      His119(GH1) region of myoglobin and near Lys72 of cytohrome c. The increased
      electron transfer rate in the presence of [Fe(CN)6]3- can be explained by that
      its binding near Lys72, firstly, provides better electrostatic interactions in
      the electron transfer complex and, besides, decreases significantly (about 2
      fold) the tunneling distance between the two hemes (two lengths of 1.7 and 1.2 nm
      instead of one of 2.9 nm).

PMID- 11449540
TI  - [Size of a human serum albumin molecule in solution].
AB  - The size of a human serum albumin molecule in aqueous solution containing 150 mM
      NaCl was studied using small-angle neutron scattering. The molecular radius of
      gyration was estimated to be 27.4 +/- 0.35 A. The compact sphere should have a
      smaller radius of gyration, whereas the popular human serum albumin model, a
      "cigar" 136 A long, should correspond to a greater radius of gyration. Possible
      shapes of the human serum albumin molecule which are in accordance with the
      results obtained, are the following: an extended ellipsoid less than 110 A of
      length or a nonsymmetrical oblate ellipsoid with a diameter of 85 A. The oblate
      ellipsoid might be close to the heart"-shaped structure of the crystalline human
      serum albumin molecule. The size of the albumin molecule does not change
      significantly as pH increases to 8.9. The possibility of the dynamic coexistence
      of various human serum albumin conformers in solution is discussed.

PMID- 11449541
TI  - [Thermodynamic model of the formation of bridges between nucleic acid molecules
      in a liquid crystal].
AB  - A thermodynamic model of the formation of bridges consisting of alternating
      daunomycin molecules and copper ions and connecting neighboring nucleic acid
      molecules in a particle of a liquid crystalline dispersion was constructed. The
      model is based on the conception that ligands are adsorbed on lattices of
      reaction centers which are formed in a liquid crystal at a particular spatial
      arrangement of adjacent nucleic acid molecules (phasing). Equations were derived
      that describe typical experimentally obtained S-shaped dependences of bridge
      concentration on the concentration of copper ions and daunomycin molecules in an
      initial solution. It was shown that dependences of this kind take place in two
      variants of the adsorption model: when the binding of daunomycin with adjacent
      nucleic acid molecules is considered to be independent on the formation of
      bridges and when bridges compete with single daunomycin molecules for the sites
      on adjacent nucleic acid molecules.

PMID- 11449542
TI  - [Interaction of lactoferrin with plasmid DNA studied by laser correlation
      spectroscopy].
AB  - The interactions of lactoferrin with plasmid DNAs substantially differing in the
      number of affine regions were studied. The dissociation constants for protein
      nucleic acid complexes were determined. The possibility of standardizing the
      conditions for preparing multicomponent systems for gene-substituting therapy by
      laser correlation spectroscopy is discussed.

PMID- 11449543
TI  - [Pathways of inclusion of isotopes 2H and 13C into exometabolites in course of
      glucose utilization by medusomycete].
AB  - The inclusion of 2H and 13C isotopes into the products of glucose utilization by
      medusomycete during its growth on deuterated media was studied by high-resolution
      NMR spectroscopy. Both unlabeled and 13C-labeled (in positions 1, 2, 6) glucose
      was used. It was shown that the glucose utilization proceeds by the classical
      Embden-Meyerhof-Parnas pathway. The incorporation of deuterium to the methyl
      group of ethanol can occur only during glucose-fructose-6-phosphate and
      phosphoenolpyruvate--pyruvate conversion. None of these stages by themselves is
      responsible for the existing distribution of deuterium atoms. The maximum
      inclusion of deuterium to the methyl group is no more than two atoms for the
      first glucose fragment (C1-C2-C3) and no more than one, for the second fragment
      (C4-C5-C6). The methylene group of ethanol is more accessible for deuterons
      because the proton surroundings of carbon atoms C2 and C5 completely changes. It
      was concluded that the maximum proton exchange occurs at positions C2 and C5; at
      positions C1, the proton exchange is lesser, and at position C6 it is the least.
      It was also shown that about 10% C1-C3 of triose leave the glycolysis cycle and
      are used in other processes.

PMID- 11449544
TI  - [Identification of minor components of medusomycete exometabolites. 1H-NMR
      spectra in 13C and deuterium substitutions].
AB  - High-resolution 1H-NMR experiments were performed on 2H/13C isotopically labelled
      metabolites of growing medusomycete culture. Some minor metabolites were
      identified and the degree of their deuterization was established. Some of these
      metabolites were shown to be present in isomeric forms. Our results demonstrated
      that glycerol was produced in the growth medium on the early stage of the system
      adaptation to the growth in D2O.

PMID- 11449545
TI  - [Effect of the surface charge on deformation dynamics in lipid membranes].
AB  - A theoretical analysis of equations of motion describing the dynamics of a
      charged spherical membrane in a viscous liquid medium was performed. It was shown
      that the curvature of the membrane substantially depends on the static surface
      charge. In addition, it was found that a local variation in surface charge
      density induces a deformation of the membrane and conversely.

PMID- 11449546
TI  - [Effect of reduced and oxidized glutathione on physico-chemical properties of
      erythrocyte membranes].
AB  - The parameters describing the structural and functional state of membranes
      depending on the level of reduced glutathione in erythrocytes were studied. It
      was shown, that the decrease in the concentration of reduced intracellular
      glutathione in erythrocytes upon metabolic depletion (prolonged incubation of
      cells at 37 degrees C in the absence of glucose) or a rapid irreversible
      depletion of glutathione with 1-chloro-2,4-dinitrobenzene enhances lipid
      peroxidation processes in membranes, inhibits the membrane-bound NAD.H
      methemoglobin reductase activity and decreases the intensity of 1,6-diphenyl
      1,3,5-hexatrien fluorescence. The data obtained suggest that the depletion of
      reduced intracellular glutathione causes changes in the physicochemical state of
      the erythrocyte membrane: the accumulation of lipid peroxidation products,
      changes in the physical state of lipid bilayer and the inhibition of membrane
      bound NAD.H-methemoglobin reductase activity.

PMID- 11449547
TI  - [Electron and proton transport in chloroplasts taking into account lateral
      heterogeneity of thylakoids. Mathematical model].
AB  - A mathematical model of a chloroplast was constructed, which takes into account
      the inhomogeneous distribution of complexes of photosystems I and II between
      granal and intergranal thylakoids. The structural and functional complexes of
      photosystems I and II, which are localized in intergranal and granal thylakoids,
      respectively, and the b/f complex, which is uniformly distributed in thylakoid
      membranes, are assumed to be immobile. The interactions between spatially distant
      electron transport complexes are provided by plastoquinone and plastocyanine,
      which diffuse in the thylakoid membrane and intrathylakoid space, respectively.
      The main stages of proton transport associated with the functioning of
      photosystem II and oxidation-reduction transformations of plastoquinone are
      considered. The model takes into account the interactions of protons with
      membrane-bound buffer groups, the lateral diffusion of hydrogen ions in the
      intrathylakoid space and in the lumen between adjacent granal thylakoids, and the
      transmembrane proton transport associated with the function of ATP synthase and
      passive leakage of protons from thylakoids outside. The numerical integration of
      two systems of differential equations describing the behavior of some variables
      in two different regions: granal and intergranal thylakoids was performed. The
      model describes adequately the kinetics of processes being studied and predicts
      the occurrence of inhomogeneous lateral profiles of proton potentials and redox
      state of electron carriers. Modeling the electron and proton transport with
      allowance for the topological features of chloroplasts (lateral heterogeneity of
      thylakoids) is important for correct interpretation of "power-flux" interactions
      and the experimentally measured kinetic parameters averaged over the entire
      spatially inhomogeneous thylakoid system.

PMID- 11449548
TI  - [Mossbauer spectroscopy of cells of cyanobacteria Synechocystis sp. PCC 6803
      devoid of photosystem I and containing inactive phycobilisomes].
AB  - Mossbauer spectra of the psaAB mutant of Synechocystis sp. PPC 6803 devoid of
      photosystem I grown in a 57Fe-containing medium were measured. The spectrum is a
      broadened doublet whose size (about 20%) and parameters (isomeric shift delta =
      0.3 mm/s and quadrupole splitting delta = 0.8 mm/s) suggest the presence of
      abundant nanoclusters of Fe3+ oxides in a superparamagnetic state tightly bound
      to the membrane. Treatment of cells with EDTA was accompanied by a substantial
      (tenfold) decrease in the amount of iron nonspecifically bound to the membrane
      and the appearance of Fe2+ localized, probably, inside cells and/or cell
      membranes. In addition, the spectrum of washed cells exhibited superfine magnetic
      splitting due to iron oxide clusters greater in size than nanoclusters present in
      the membrane prior to EDTA treatment.

PMID- 11449549
TI  - [Photoinactivation of bacteriophage PM2 by cyanine dyes].
AB  - Photoinactivation of the lipid-containing bacteriophage PM2 by visible light and
      cyanine dyes (carbo- and dicarbocyanines), aluminum phtalocyanine tetrasulfonate
      and methylene blue was studied. It was concluded that cyanine dye aggregates
      adsorbed on phage particles and oxygen are essential for phage photoinactivation.

PMID- 11449550
TI  - [Dielectric characteristics of intact and copper-modified bacteria Escherichia
      coli].
AB  - The dielectric parameters of the intact and Cu(2+)-modified concentrated
      Escherichia coli populations in the frequency range of alternating current 20 Hz
      100 MHz were studied. It was found that Cu(2+)-ions in low concentrations, which
      are mainly absorbed by active centres of the outer cell surface, change the
      dielectric characteristics of the inner membrane and simultaneously increase the
      conductivity of plasma membrane in the frequency-independent region 10(5)-10(6)
      Hz. It was concluded that the disturbances in the barrier properties of plasma
      membrane by the action of Cu2+ are closely related to changes in the dielectric
      parameters of intact bacteria.

PMID- 11449551
TI  - [Mechanism of the effect of weak electromagnetic fields on the living body].
AB  - By using the model conceptions of the dielectric polarization theory, a new
      mechanism for the effect of electromagnetic field was proposed. The model enables
      one to explain the experimentally observed influence of low-frequency weak
      electromagnetic field on biological objects. It was shown that, at the cellular
      and subcellular levels, an increase in the intensity of the electric component of
      external electromagnetic field can occur. The magnitude of this increase is
      determined by the ratio of the contributions of the medium polarization and the
      depolarizing factor (which depends on body shape) to the total effect. As a
      result of this increase, a potential comparable with intrinsic biological values
      can be generated on neuron membranes, which must elicit nervous and physiological
      responses of the organism.

PMID- 11449552
TI  - [Effect of light of various spectral composition on kinetics of changes in a
      green leaf resistivity].
AB  - The kinetics of changes in the resistance of a green leaf by the action of
      exciting light was studied. It was shown that the illumination-induced changes in
      leaf conductance are mainly due to an elevation of temperature caused by the
      absorption of light energy. Based on the experimental results, the fraction of
      absorbed light energy converted into heat calculated under assumption that
      heating of the leaf across the thickness is uniform. It was found that the
      fraction of absorbed energy converted into heat does not depend on the intensity
      of radiation in the IR range and increases with decreasing intensity of
      photosynthetically active radiation. An explanation of the phenomenon is
      proposed, which is based on that in reality the heating of the leaf across the
      thickness is nonhomogeneous and this inhomogeneity of heating becomes more
      pronounced upon photoinduced changes in absorption resulting from a decrease in
      photosynthetically active radiation. It was shown that nonphotochemical
      fluorescence quenching does not substantially affect the leaf conductance at
      intensities of photosynthetically active radiation not higher than 200 Wt/m2.

PMID- 11449553
TI  - [Principles of spatial organization of cellular sheets].
AB  - The principles of the spatial organisation of epithelial sheets are described,
      and a new approach to studying their histoarchitecture is proposed. The approach
      is based on the concept of modular structure of tissues and consists in
      constructing a family of topological and geometrical models of tissue structure
      and their experimental verification. Theoretical evidence was obtained that at
      least 11 topological variants of cell mosaic patterns can be realized in simple
      epithelia but not one as has been suggested so far. Nine variants of epithelial
      mosaics predicted have been found experimentally in various animals, and the
      discovery of the other two is expected in the future. New thus far unknown
      properties of tissues such as translation symmetry and stoichiometry of the
      composition were described. By using this approach, it is possible to predict and
      find new variants of topology of multirow and multilayer epithelia and prognose
      their changes during normal and pathological morphogenesis.

PMID- 11449554
TI  - [Two-dimensional reconstruction of birefringence map of the skeletal muscle
      sarcomere in relaxed and rigor states studied by interference microscopy].
AB  - A new method of automatized quantitative interferometry of skeletal muscle fibers
      was developed for the investigation of birefringence. A device based on the
      Linnic microscope was constructed to obtain phase images, which are two
      dimensional pictures of birefringence. For the first time, two-and-three
      dimensional maps of both total birefringence and birefringence for individual
      sarcomeres in the central part of muscle fiber were visualized using large
      databases. It was shown that total birefringence of fibers at rest length in the
      rigor state was lower as compared with the relaxed. Birefringence values from
      individual sarcomere interferograms revealed also that normalized A-disk
      birefringence was lower in the rigor state. The results obtained could be
      explained by a decrease of thick filaments anisotropy, due to the moving away of
      myosin heads from the rod during transition into the rigor state.

PMID- 11449555
TI  - [A method for reconstruction of pathological changes in the volume of a living
      body].
AB  - A new method of contact thermography (intrograph) was developed. The method
      allows one to establish the temperature in any region of the body. The computer
      program provides an uninvasive and safe way of comparison of thermograms in time.
      The obviously known biomedical parameters allow one to locate and characterize
      pathology foci. The accuracy of one temperature measurement is not worse than
      0.01 deg at a measurement time of about one second.

PMID- 11449556
TI  - [Errors in measurement of section areas and perimeters of microvessels from their
      profiles in sections for light and electron microscopy].
AB  - The error of measuring the section areas and perimeters of microvessels was
      estimated, which is due to a deviation of the section plane from the direction
      perpendicular to the longitudinal axis of microvessels. The estimates of the
      microvessel nonperpendicular sectioning error correspond to the case of three
      dimensional isotropic distribution of microvessels without their own
      eccentricity. Only those microvessel profiles are selected for morphometry that
      meet the condition theta min < or = b/c < or = 1.00, where b is the minor and c
      is the major radii of microvessel profile on a section, and theta min is the
      tolerance for profile nonperpendicularity.

PMID- 11449557
TI  - [Effect of magnetic field on excitation propagation in a nerve fiber innervating
      a blood vessel].
AB  - It was shown that external magnetic field indirectly affects the blood flow due
      to the increments of local currents in the surroundings of action potentials that
      propagate along nerve fibres innervating the smooth muscle cells of the vessel
      wall. This reduces their tension due to nonconcurrent propagation of excitation
      in space and to changes in the frequency of action potentials. The dependence of
      this effect on the electrophysiological parameters is estimated.

PMID- 11449558
TI  - [A novel experimental method for evaluation of effect of nitrites on blood
      deoxygenation kinetics].
AB  - A new method for studying the oxygen-binding properties of blood is proposed,
      which is based on the analysis of transient processes on oxygen electrodes. The
      method was used to study the effect of sodium nitrite on the kinetics of
      dissociation of oxyhemoglobin in rat blood. It was shown that the rate of oxygen
      transport decreases at nitrite concentrations 1-5 mg/100 g body weight.

PMID- 11449559
TI  - [Estimation of the excitation reduction following spike generation in the frog
      central auditory neurons].
AB  - A method for the estimation of the spike probability reduction caused by a
      preceding spike is proposed for central auditory neurons. The method is based
      upon a comparison of the normalized poststimulus time histogram with the
      normalized latency histogram and the expected probability function. For the
      solution of the superfluous system of linear equations, the least-squares fit was
      used. The result (temporal course of discharge history effect) was then
      approximated by a function that included several initial zero points (absolute
      refractory period). Three points were approximated by the error function (short
      relative refractory period) and all following points were equal to one. The only
      variable parameter was the number of zero points, the duration of refractoriness.
      This method was tested on a descriptive model of an auditory neuron in which each
      interspike interval consists of an absolute refractory period and a random-length
      waiting time to the next spike. The estimation of the model absolute refractory
      period by the proposed method was in reasonable coincidence with input data after
      several thousands of stimulus presentations. The same method was used for the
      estimation of dead-time in 87 single units of the midbrain auditory region of the
      frog. A great variability of refractory time (from less than 2 ms to more than 18
      ms) was shown. The duration of refractoriness correlated with the latency period
      of neurons.

PMID- 11449560
TI  - [Localization of a sum of acoustic signals in air by the northern fur seal].
AB  - The localization of a sum of acoustic signals by two northern fur seals in air
      depending on sound parameters was investigated using the method of instrumental
      conditioned reflexes with food reinforcement. It was found that sound perception
      of northern fur seal proceeds by the binaural mechanism. The time/intensity
      interchange coefficient was 570 microseconds/dB for series of clicks (with
      amplitude maximum at 1 kHz) and 250 microseconds/dB for tonal impulses with a
      frequency of 1 kHz. With click amplitudes being equal, the number of approaches
      of the animal to the source of the first signal reached a 75% level at a delay of
      the second signal 0.07 ms (the minimum delay); with a delay of 6 ms (the maximum
      delay) and more, the fur seal, probably hears two separate signals. The minimum
      delay depended little on the duration of tonal impulses (with a frequency of 1
      kHz) and was 0.3-0.7 ms; the maximum delay was 9-11 ms for tonal impulses with a
      duration of 3 ms and 37-40 ms with impulse duration 20 ms. The precedence effect
      became apparent at a greater delay for smooth fronts of impulses than for
      rectangular fronts.

PMID- 11449561
TI  - [Effect of additional loading on kinematics and hydrodynamics of dolphins].
AB  - The results of comparative measurements of hydrodynamic resistance of a solid
      model of dolphin and of additional load imitating an autonomous apparatus placed
      on the dolphin body are presented. The loading included cylinders (with rounded
      anterior and posterior ends) and spheres. They were fixed on the dorsal fin of
      the dolphin model in such a way that the interrelationship between the load and
      the model by a water stream minimal. In several experiments, a thick ring (dr =
      10 mm) was fixed in the region of the dolphin respiratory opening to reach the
      turbulence of the boundary layer. The dolphin model with loads was towed in a
      speed range between 1.0 and 4.5 m/s. It was shown that the hydrodynamic
      resistance of additional loads is comparable with the resistance of the solid
      dolphin model. For the entire spectrum of loading in the preset range of towing
      speeds, the coefficient of hydrodynamic resistance of loading (according to the
      area of the wet body surface) was from 10 to 145% of the coefficient of the
      dolphin model resistance. It was assumed that the results of the measurements of
      kinematics and hydrodynamic characteristics of a freely-swimming dolphin can
      substantially differ from the results obtained on a dolphin carrying devices (at
      restricted power of the animal). Similar problems can also arise if the animals
      will carry devices with a higher hydrodynamic resistance.

PMID- 11449562
TI  - [Left-handed helix conformation of poly-L-proline II type in globular proteins.
      Statistics of incidence and a role of sequence].
AB  - Regions of left-handed polyproline II type conformation in globular proteins were
      studied throughout the PDB bank. The length and sequence of corresponding
      fragments were analyzed. It was found that a lot of tetrapeptides (from
      combinatorial possible ones) show the tendency to be included in the left-handed
      helices. Much more tetrapeptides do not occur in this structure type.

PMID- 11449563
TI  - [Assisted bleaching: presentation of the method in a case report].

PMID- 11449564
TI  - [Periradicular surgery. I].

PMID- 11449565
TI  - Design and implementation of a collaborative molecular graphics environment.
AB  - During the determination of macromolecular structures, scientists routinely use
      complex graphics software to display various representations of the molecule of
      interest. Once the structure determination is complete, coordinates are deposited
      in the Protein Data Bank (PDB), from where anyone with an Internet connection may
      download and view them or request them on CD-ROM. However, the currently
      available visualization software is such that causal users, whose expertise may
      not be in structure determination, often cannot obtain useful images of
      interesting molecules without expending considerable time and effort. Existing
      visualization software is generally very complex, requiring a high degree of
      familiarity to obtain the best results, or else it is too simplistic to provide
      users with the level of customizability needed to get the most out of the atomic
      coordinates. Few of the existing software packages have the capability for
      collaborative visualization via the Internet. These and other issuses are being
      addressed by the Molecular Interactive Collaborative Environment (MICE) project
      (http://mice.sdsc.edu/). The core of the MICE project is the MICE application, an
      interactive molecular structure viewer with built-in collaborative capabilities.
      MICE not only addresses the issues of usability and flexibility but also extends
      the role of traditional visualization tools by allowing multiple users to view,
      manipulate, and interact with a single representation of a macromolecular
      structure. MICE is written entirely in Java, using the Java3D extensions for
      rendering and manipulation of the three-dimensional scene, and the Common Object
      Request Broker Architecture (CORBA) communications suite to enable collaborative
      manipulation of that scene.

PMID- 11449566
TI  - Accurate prediction of the bound conformation of galanthamine in the active site
      of Torpedo californica acetylcholinesterase using molecular docking.
AB  - The alkaloid (-)-galanthamine is known to produce significant improvement of
      cognitive performances in patients with the Alzheimer's disease. Its mechanism of
      action involves competitive and reversible inhibition of acetylcholinesterase
      (AChE). Herein, we correctly predict the orientation and conformation of the
      galanthamine molecule in the active site of AChE from Torpedo californica
      (TcAChE) using a combination of rigid docking and flexible geometry optimization
      with a molecular mechanics force field. The quality of the predicted model is
      remarkable, as indicated by the value of the RMS deviation of approximately 0.5A
      when compared with the crystal structure of the TcAChE-galanthamine complex. A
      molecular model of the complex between TcAChE and a galanthamine derivative,
      SPH1107, with a long chain substituent on the nitrogen has been generated as
      well. The side chain of this ligand is predicted to extend along the enzyme
      active site gorge from the anionic subsite, at the bottom, to the peripheral
      anionic site, at the top. The docking procedure described in this paper can be
      applied to produce models of ligand-receptor complexes for AChE and other
      macromolecular targets of drug design.

PMID- 11449567
TI  - Computational analysis of Thr203 isomerization in green fluorescent protein.
AB  - Green fluorescent protein (GFP) is an extensively used fluorescent tag.
      Photoisomerization between two spectroscopically distinct states in wild-type GFP
      is responsible for its two visible absorption bands at 398 nm (A) and 475 nm (B).
      We have used molecular mechanics and database analysis to support the suggestion
      of other researchers that the anionic form of the GFP chromophore is responsible
      for the B absorption band, while the phenol form is responsible for band A. The
      anionic (-Otyr, Nimid, Glu222H) species is the only form that has a low energy
      pathway allowing for isomerization of Thr203 to a conformation where it
      stabilizes the phenolate form and is therefore the most likely species
      responsible for the B absorption band. The rotation of the Thr203 side-chain is
      restricted; this may be significant in the formation of the intermediate state
      which is central to the photoisomerization. Our calculations support the most
      commonly accepted mechanism for photoisomerization, and we have shown that the
      201LSTQS205 sequence does not allow a g+ conformation for Thr203.

PMID- 11449568
TI  - H-BloX: visualizing alignment block entropies.
AB  - H-BloX is a web-based JavaScript application that allows the calculation and
      visualization of Shannon information content or relative entropy (Kullback
      Leibler 'distance') within sequence alignment blocks. The application was
      designed for use in both teaching and research. Amino acid, nucleic acid
      sequences, or any other type of aligned chemical structures may serve as the
      input. Various interpretations of the meaning of 'entropy' or 'information
      content' are possible, including treatment as a chemical diversity measure or the
      degree of feature conservation. For analysis of numerical data by H-BloX, values
      must be converted to a user-defined character alphabet before computation of
      entropy or information content. H-BloX was successfully applied to feature
      identification in Escherichia coli signal peptides and their cleavage sites.
      Characteristics known features became visible, e.g., the hydrophobic core region
      and the well-known '-3,-1' cleavage site pattern. Based on the H-BloX analysis,
      the hydrophobic core is centered at amino acid residue position 13, counting from
      the N-terminal end of the protein precursor sequence. This result was obtained by
      using a built-in feature of H-BloX that enables conversion of amino acid
      sequences to a different alphabet that is based on hydrophobicity assignments. H
      BloX can be accessed online or downloaded as HTML/JavaScript at
      http://bopwww.biologie.uni-freiburg.de/~bioinfo/HBloX/html/index.html.

PMID- 11449569
TI  - Hydrophobicity and functionality maps of farnesyltransferase.
AB  - Farnesyltransferase (FTase) catalyzes the attachment of a 15-carbon isoprenoid
      moiety, farnesyl, through a thioether linkage to a cysteine near the C-terminus
      of oncogenic Ras proteins. These transform animal cells to a malignant phenotype
      when farnesylated. Hence, FTase is an interesting target for the development of
      antitumor agents. In this work we first investigate the active site of FTase by
      mapping its hydrophobic patches. Then the program SEED is used to dock functional
      groups into the active site by an exhaustive search and efficient evaluation of
      the binding energy with solvation. The electrostatic energy is SEED is based on
      the continuum dielectric approximation and consists of screened intermolecular
      energy and protein and fragment desolvation terms. The results are found to be
      consistent with the sequence variability of the tetrapeptide substrate. The
      distribution of functional groups (functionality maps) on the substrate binding
      site allows for identification of modifications of the tetrapeptide sequence that
      are consistent with potent peptidic inhibitors. Furthermore, the best minima of
      benzene match corresponding moieties of an inhibitor in clinical trials. The
      functionality maps are also used to design a library of disubstituted indoles
      that might prevent the binding of the protein substrates.

PMID- 11449570
TI  - Intramolecular C-H--O interaction between lactam oxygen and N-alkyl protons.
AB  - We report evidence of an unusual C-H--O interaction between an alpha-methylene
      hydrogen of the alkylamine chain of substituted (N,N-dimethylamino)propyl
      azetidinones, substituted (N,N-dimethylamino)propyl-thiazolidinones and
      substituted (N,N-dimethylamino)propyl-thiazinone and the lactam carbonyl oxygen.
      NMR analysis results, supported by molecular mechanic predictions, were in
      agreement with ab initio calculations. The observed interaction shorting the
      nitrogen-nitrogen distance in the H1-histamine antagonist, 2-(4-methylphenyl)-3
      [3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-one (1) could explain its fitting
      with the H1-antihistaminic pharmacophoric model and the high antihistaminic
      activity.

PMID- 11449571
TI  - Rapid atomic density methods for molecular shape characterization.
AB  - Two methods for rapid characterization of molecular shape are presented. Both
      techniques are based on the density of atoms near the molecular surface. The Fast
      Atomic Density Evaluation (FADE) algorithm uses fast Fourier transforms to
      quickly estimate densities. The Pairwise Atomic Density Reverse Engineering
      (PADRE) method derives modified density measures from the relationship between
      atomic density and total potentials. While many shape-characterization techniques
      define shape relative to a surface, the descriptors returned by FADE and PADRE
      can measure local geometry from points within the three-dimensional space
      surrounding a molecule. The methods can be used to find crevices and protrusions
      near the surface of a molecule and to test shape complementarity at the interface
      between docking molecules.

PMID- 11449572
TI  - Superimposition-based protocol as a tool for determining bioactive conformations.
      I. Application to ligands of the glycinergic receptor (GlyR).
AB  - The natural templates (NT) approach, which is a superimposition-based protocol
      that has been successfully employed in several studies, is here applied to
      ligands of the glycine ligand-gated ion channel receptor. Bioactive conformations
      for glycine and its analogs were obtained using strychnine (a natural and
      specific competitive antagonist) as template. Experimental evidence was used to
      guide the superimposition protocol. Three essential regions have been defined in
      strychnine's structure that serve as a pharmacophore for agonist and antagonist
      activities. Reasonable alignments of known ligands were found in the majority of
      the cases. Molecular mechanics (i.e., conformational searches for the relatively
      flexible ligands) and molecular dynamics (for relatively rigid ligands such as
      strychnine and 5,6,7,8-tetrahydro-4H-isoxazolo[3,4-d]azepin-3-ol) were used to
      assess the energetic accessibility of the proposed bioactive conformations.

PMID- 11449573
TI  - Molecular dynamics simulations of alpha-D-Manp-(1-->3)-beta-D-Glcp-OMe in
      methanol and in dimethyl sulfoxide solutions.
AB  - Molecular dynamics simulations have been performed of the disaccharide alpha-D
      Manp-(1-->3)-beta-D-Glcp-OMe in two different solvents, namely in methanol and in
      dimethyl sulfoxide. The conformation of the disaccharide is similar to that
      previously determined in water. The three-dimensional structure around the solute
      was investigated by geometric hydrogen bonding criteria, radial distribution
      functions, coordination number analysis, residence times for hydrogen bonds, and
      spatial distribution functions. Differences and similarities between methanol and
      the aprotic dimethyl sulfoxide as solvent are analyzed.

PMID- 11449574
TI  - Application of promolecular ASA densities to graphical representation of density
      functions of macromolecular systems.
AB  - In this article we report the application of the Promolecular Atomic Shell
      Approximation (Promolecular ASA) to the graphical representation of the density
      function (DF) of large macromolecular systems. Promolecular ASA DF, constructed
      from previously computed and fitted atomic densities, provides a fast and
      practical representation of Molecular IsoDensity Contours (MIDCOs). These
      representations can be extended to macromolecular systems composed by > 1000
      atoms easily and with low computational costs, allowing the visualization of
      protein DF. The method is at first presented with a small molecule (2,4,6
      trinitrophenol), comparing the resulting ASA MIDCOs with direct ab initio
      contours. For macromolecular tests the Promolecular ASA densities are also
      applied to the generation of macromolecular density surfaces of two proteins:
      myoglobin (2541 atoms) and gene V protein (1362 atoms).

PMID- 11449575
TI  - Theoretical hydrogen bonding parameters for drug design.
AB  - Hydrogen bonding interactions play a major role in many chemical and biological
      processes. This article describes the development of a method for the
      quantitative estimation of the hydrogen-bonding donor strengths of OH/NH moieties
      and of the hydrogen bonding acceptor strengths of O/N atoms in different chemical
      structures. The method is based on the correlation of experimentally observed
      hydrogen-bonding strengths with quantum-mechanical derived properties, calculated
      on the acceptor atom (for hydrogen-bond acceptors) and on the heavy atom attached
      to the donor hydrogen (for hydrogen-bond donors). The properties giving the best
      correlation with the experimental hydrogen bonding scales were electrophilic
      superdelocalizability and self-atom polarizability. The best equations found have
      been implemented in a Web-based tool for hydrogen-bond strength prediction.

PMID- 11449576
TI  - Crystallographic autostereograms.
AB  - Perspective drawings of crystal structures can be presented as autostereograms
      (or single-image stereograms), and their performance for in-depth perception is
      similar or even more advantageous than of stereopairs. The autostereograms offer
      a convenient means for realistic insight into crystal structures without
      excessive size reduction of their drawings, as required when preparing
      stereopairs; thus structures either as simple as elements or as complex as
      proteins can be illustrated in enhanced resolution. The mathematical background
      and guidelines for preparing crystallographic autostereograms are described.

PMID- 11449577
TI  - Sudden death in heart failure associated with reduced left ventricular function:
      substrates, mechanisms, and evidence-based management, Part II.

PMID- 11449578
TI  - Unusual cause of supraventricular tachycardia after acute myocardial infarction.

PMID- 11449579
TI  - Successful pediatric stenting of a nonthrombotic coronary occlusion as a
      complication of radiofrequency catheter ablation.
AB  - This is a case of a right coronary artery occlusion complicating a RF catheter
      ablation of a posteroseptal accessory connection in an 8-year-old boy. After
      multiple balloon angioplasty attempts in the occluded vessel, only transient
      patency was achieved. The occlusion was successfully treated with placement of an
      intracoronary stent.

PMID- 11449580
TI  - Successful surgical ablation of sustained ventricular tachycardia associated with
      mitral valve prolapse guided by a multielectrode basket catheter.
AB  - Ventricular tachycardia occurs frequently in patients with mitral valve prolapse.
      If antiarrhythmic drug therapy fails or mitral valve surgery is indicated,
      concomitant arrhythmia surgery may be considered. This report describes the first
      clinical use of an atrial transseptally inserted multielectrode basket catheter,
      placed across the mitral valve, to guide intraoperative mapping and ablation of
      monomorphic sustained ventricular tachycardia in association with mitral valve
      prolapse. Endocardial covering and signal quality of this percutaneous mapping
      catheter were of good quality, allowing an accurate localization of the site of
      origin of the tachycardia.

PMID- 11449581
TI  - Transvenous left atrial and left ventricular pacing in Ebstein's anomaly with
      severe interatrial conduction block.
AB  - The implantation of permanent pacemakers in patients with congenital heart
      disease can be challenging. This report describes the complexity of pacemaker
      implantation in a patient with Ebstein's disease, tricuspid valve replacement,
      and right atrial abnormalities like severe intra- and interatrial conduction
      block that prevented dual chamber pacing from conventional sites. This case
      illustrates the promising possibility to circumvent the interatrial conduction
      block with single left atrial pacing instead of biatrial pacing which was not
      suitable here.

PMID- 11449582
TI  - Late fatal right ventricular perforation as complication of permanent pacing
      leads.
AB  - Perforation of the right ventricle during placement of pacing electrodes is a
      well-documented complication. Most of these perforations occur intraoperatively
      and rarely cause symptoms. This case report describes a fatal cardiac perforation
      that occurred 10 days after implantation of a permanent cardiac pacemaker. This
      complication should be considered as one of the potential mechanisms responsible
      for the high rate of sudden death observed in paced patients during the first
      year after pacemaker implantation.

PMID- 11449583
TI  - Sinus node reentrant tachycardia in a neonate.
AB  - A neonate presented with paroxysmal atrial tachycardia. Transesophageal
      electrophysiological study demonstrated sinus node reentrant tachycardia, which
      was induced and terminated with programmed electrical stimulation. The
      tachycardia would also terminate in the atrium with adenosine. Empiric digoxin
      treatment successfully suppressed the tachycardia which then recurred with
      discontinuation of the digoxin at 6 weeks. The child was retreated with digoxin
      with no further recurrences for 18 months. Transesophageal electrophysiological
      study at 20 months showed prolonged sinus node recovery times and no inducible
      arrhythmias. The child has remained free of arrhythmias at 4 years.

PMID- 11449584
TI  - Pneumomediastinum and subcutaneous emphysema from pacemaker placement.
AB  - Percutaneous insertion of permanent pacemaker leads through the subclavian vein
      is an alternative to the cephalic vein approach. A rare occurrence and successful
      conservative management of extensive pneumomediastinum and subcutaneous emphysema
      without concomitant pneumothorax resulting from permanent transvenous pacemaker
      insertion in an 80-year-old man with syncope and arrhythmia is reported.

PMID- 11449585
TI  - Routine arrhythmia inductions for ICD follow-up: are they obsolete?

PMID- 11449586
TI  - Contribution of a pacemaker bradycardia detection algorithm in the study of
      patients with carotid sinus syndrome.
AB  - While carotid sinus syndrome (CSS) is often suspected as a cause of syncope in
      the elderly, whether it represents an indication for cardiac pacing may remain
      uncertain. Bradycardia algorithms included in pacemakers are now able to
      establish a precise relationship between spontaneous asystole and occurrence of
      symptoms and strengthen the indication for permanent pacing. This study included
      seven men and three women (70.5 +/- 7.3 years of age) who, over an average period
      of 54.1 +/- 17 months, had suffered from syncope (12.6 episodes/patient) and
      presyncope (11.2 episodes/patient) attributed to pure cardioinhibition (2
      patients) or mixed CSS (8 patients). Other sources of symptoms were excluded by
      thorough clinical evaluations, including Holter monitoring, echocardiography, and
      electrophysiological testing. All patients received a CHORUS 6234 pacemaker, the
      memory of which includes a dedicated bradycardia detection algorithm capable of
      storing atrial and ventricular chains, and date and time of the last ten pauses
      and/or bradycardic events. After a initial period of 14.7 +/- 8 months, during
      which symptoms were suppressed, the bradycardia algorithm was activated. From
      then on, a cumulative increase in the number of patients presenting with diurnal
      pauses was measured (1 month, n = 0; 3 months, n = 6; 9 months, n = 7; 2 years, n
      = 8). Fourteen episodes of diurnal asystole were recorded. The mean duration of
      the longest episodes of spontaneous ventricular standstill was 6,319 +/- 1,615 ms
      and was due to sinoatrial block (n = 7), atrioventricular block (n = 5), and a
      combination of both (n = 2). In conclusion, activation of the CHORUS bradycardia
      algorithm allowed confirmation of the appropriateness of permanent pacing in a
      majority of patients suffering from CSS.

PMID- 11449587
TI  - Effect of different pacing protocols on the induction of atrial fibrillation in a
      transvenously paced sheep model.
AB  - In different animal models rapid atrial stimulation led to a shortening and
      maladaptation to rate of the atrial effective refractory period (AERP). This
      atrial electrical remodeling resulted in an increased vulnerability to atrial
      fibrillation (AF). These experimental findings formed the rationale for a
      stringent pursuit of sinus rhythm in patients with AF, since this would prevent
      or reverse atrial remodeling. This study tested the hypothesis that a reduction
      of arrhythmia burden would lead to a decreased vulnerability for AF. Different
      rapid atrial pacing protocols in a sheep model were used. During 15 weeks, 13
      animals were continuously rapid paced and 7 animals were intermittently burst
      paced, resulting in rapid atrial activation during 100% versus 33 +/- 4% of the
      time, respectively. In the continuously paced group, 77% of the animals developed
      sustained AF (i.e., > 1 hour) versus only 29% in the burst-paced group (P <
      0.05). However, there was no difference in mean AERP shortening over time, nor
      maximal AERP shortening per animal, between both protocols. Minimal AERP was 103
      +/- 5 ms in the continuously paced group and 107 +/- 5 in the burst-paced group
      (P = NS). Significant changes could be identified in effect on P wave duration,
      AVN function, and atrial dilation. Conduction slowing was more pronounced in the
      continuously paced group with a maximal P wave duration of 136 +/- 4 ms in this
      group versus 116 +/- 5 in the burst-paced group (P < 0.05). In the continuously
      paced group, the right atrial area significantly increased from 2.5 +/- 0.1 cm2
      at baseline to 4.2 +/- 0.2 cm2. In the burst-paced group there was no significant
      atrial dilatation (from 2.6 +/- 0.1 to 2.8 +/- 0.1 cm2). In conclusion, limiting
      atrial arrhythmia burden slowed the development of sustained AF in this sheep
      model. This was not mediated by a decreased influence on atrial refractoriness
      but seemed to be dependent on smaller changes in atrial conduction and
      dimensions.

PMID- 11449588
TI  - Radiofrequency catheter ablation using long coiled electrodes: impact of
      irrigation on lesion dimensions and incidence of coagulum formation.
AB  - Ablation catheters with multiple long coiled electrodes have been recently
      developed to induce continuous linear lesions for the treatment of atrial
      fibrillation. The efficacy and safety of ablation catheters with multiple long
      coiled electrodes has not been evaluated. The aim of the present in vivo study
      was to investigate the influence of saline irrigation on lesion dimensions and
      coagulum formation during RF current ablation using those ablation catheters. In
      14 anesthetized sheep, the thigh muscle was prepared as a cradle and filled with
      heparinized blood (37 degrees C). The quadripolar coiled ablation catheter
      (electrode length 7 mm, electrode distance 2 mm) was placed parallel to the
      muscle with standardized 10-g contact pressure. RF current energy was delivered
      sequentially temperature-(70 degrees C) or power-controlled (10, 20, 30, or 40 W)
      with additional irrigation of the electrode (10 mL/min normal saline) for 90
      seconds. Forty-two of 129 RF current lesions were induced by temperature
      controlled and 87 by irrigated ablation. Except for three lesions following low
      energy irrigated application (10 W), all lesions were continuous. Significantly
      larger lesions following irrigated RF current applications were produced with a
      power output of 30 W (depth 0.74 +/- 0.13 cm, width 0.78 +/- 0.13 cm) and 40 W
      (depth 0.75 +/- 0.16 cm, width 0.92 +/- 0.28 cm) as compared to 20 W (depth 0.47
      +/- 0.13 cm, width 0.82 +/- 0.22 cm). Coagulum formation adherent to the
      electrode was exclusively observed following 18 of 42 nonirrigated RF current
      ablations. In conclusion, irrigated coiled ablation electrodes induce continuous
      linear lesions with a power output of 20-40 W. The risk of coagulum formation at
      the coiled electrode can be avoided by irrigation.

PMID- 11449589
TI  - A simplified approach to temporary DDD pacing using a single lead, balloon-tipped
      catheter with overlapping biphasic impulse stimulation.
AB  - Temporary DDD pacing offers significant hemodynamic benefits in emergency
      management of bradyarrhythmias but is underused because of its complexity (two
      leads) and unreliability. Single lead VDD pacing with atrial sensing via a
      floating dipole is feasible, but atrial pacing is limited by high thresholds and
      phrenic nerve stimulation (PNS). Overlapping biphasic impulse (OLBI) stimulation
      may avoid these problems. The authors designed a single lead balloon-tipped
      catheter for temporary transvenous DDD pacing, incorporating noncontact atrial
      dipoles for OLBI stimulation. This catheter was deployed using fluoroscopic
      guidance in 74 patients (43 men, 31 women) with mean age 56.9 +/- 17.0 years.
      Pacing parameters were assessed at implantation and follow-up. The median
      procedural time was 6.6 (range 1.2-25.0) minutes and fluoroscopy time 1.9 (range
      0.2-7.8) minutes. Stable VDD pacing was achieved in all cases. Atrial capture was
      achieved in 73 of 74 cases with both modes at maximum output but was restricted
      by PNS at outputs below atrial capture threshold in 3 of 74 cases with OLBI and
      10 of 74 cases with standard bipolar mode (P = 0.04). At outputs > or = 1.0 V
      above atrial threshold, reliable DDD pacing without PNS was achieved and
      maintained in 67 (91%) of 74 patients in OLBI compared to 53 (72%) of 74 patients
      in bipolar mode (P = 0.003). Pacing parameters were stable during follow-up
      (median 53 hours, range 6-168 hours). In conclusion, the single lead catheter
      with OLBI stimulation allows temporary VDD and DDD pacing without PNS to be
      achieved in > 90% of patients. This rapid and convenient approach should
      facilitate DDD pacing in emergency settings.

PMID- 11449590
TI  - Do battery depletion indicators reliably predict the need for pulse generator
      replacement?
AB  - The aim of this study was to test the validity of battery depletion indicators to
      forecast end of service (EOS) in dual chamber pulse generators (PG). Two
      additional approaches for prediction of EOS were evaluated as well: the real-time
      telemetry of cell impedance and a battery stress test (BST) that used a
      transitory increase in pacing rate. The study population consisted of 119
      patients with Intermedics dual chamber PG models Cosmos II and Relay, in which
      cell impedance had exceeded 2.5 k omega. The patients were followed in 6-month
      intervals. If the interrogation of the PG or the BST prompted the appearance of
      the intensified follow-up indicator (IFI), the next follow-up was scheduled
      within 2 months. PG replacement was performed on physician's discretion or
      immediately on appearance of the elective replacement indicator (ERI), regardless
      of the method of ERI provocation. During a period of 2 years/and 9 months, 33
      patients underwent PG replacement. Out of 21 patients with positive ERI
      indicators, only 5 had positive warning indicators of approaching battery
      depletion in the preceding follow-up (IFI during BST, n = 4; ERI during BST n =
      1). The majority of patients (n = 16, 76%) revealed ERI without prior activation
      of IFI, neither spontaneous nor during the BST. Four of these 16 ERI-positive
      patients had cell impedance values far below the ERI limits of the manufacturer.
      Based on battery depletion indicators, an exact prediction of EOS of dual chamber
      pacemakers is not possible. Measuring battery impedance allows for a statistical
      estimation of remaining service life but it may be misleading in the individual
      case. A BST that is based on a temporary increase of pacing rate is invalid in
      forecasting battery depletion. As activation of the ERI can trigger an abrupt
      change to the VVI backup mode, pacemaker dependent patients with low programmed
      basic pacing rates may be hemodynamically compromised by an unexpected activation
      of ERI. Close monitoring intervals and PG replacement before appearance of the
      ERI is recommended in those patients.

PMID- 11449591
TI  - Clinical use of permanent pacemaker for conversion of intraatrial reentry
      tachycardia in children.
AB  - The use of the implanted atrial-based pacemaker to overdrive postsurgical
      intraatrial reentry tachycardia (IART) was evaluated in a large group of
      pediatric patients over a 14-year study period. The authors sought to determine
      the feasibility of this noninvasive technique in the management of this
      specialized population and to determine factors associated with successful
      conversion. They examined 128 manual overdrive attempts performed on 22
      consecutive patients. There were 10 patients with post-Fontan repair, 7 with post
      Mustard/Senning procedure, and 5 with miscellaneous lesion types. The number of
      IART episodes for overdrive pacing per patient ranged from 1 to 15. The first
      overdrive pacing attempt was successful in 63% (14/22) of the patients. The mean
      IART cycle length was 278 +/- 59 ms. The mean pacing rate for effective
      conversion of IART was 66 +/- 10% faster than the IART rate. By controlling for
      repeated measures for individual patients, three factors were found to be
      independently associated with a successful outcome: (1) lesion type other than
      Fontan surgery (P = 0.007), (2) lack of acceleration of IART with the overdrive
      attempt (P < 0.001), and (3) patient use of amiodarone with attempt (P = 0.005).
      There were three procedural complications: two inadvertent overdrive pacing
      episodes, and one episode of acceleration of IART cycle length and conduction
      resulting in need for cardioversion. Manual pacemaker overdrive conversion of
      IART is a useful adjunct in the management of postsurgical IART in the pediatric
      population and should be considered as an initial treatment option.

PMID- 11449592
TI  - Incidence of T wave alternation after acute myocardial infarction and correlation
      with other prognostic parameters: results of a prospective study.
AB  - Tachycardia induced alternation of the T wave (TWA) has been associated with
      arrhythmia morbidity in mixed patient populations. However, less is known
      concerning the general incidence of TWA and its usefulness in risk stratification
      early after acute myocardial infarction (MI). TWA was prospectively and
      systematically assessed in 140 consecutive patients 15 +/- 6 days after acute MI
      and prior to discharge. Results of TWA measurements were compared to other
      noninvasive risk markers, LV function, and coronary angiography. Sustained TWA
      was present at rest or inducible during exercise in 27% of patients. The patient
      specific heart rate for the onset of TWA was 98 +/- 9 beats/min. After
      multivariate analysis, TWA correlated with age (P = 0.02) and LV function (P =
      0.002) and occurred more often in patients after nonanterior MI (P = 0.03). Acute
      results of Holter monitoring, late potentials by signal-averaged ECG, and heart
      rate variability were unrelated to the TWA status. During follow-up (451 +/- 210
      days) two major arrhythmic events occurred. The incidence of TWA early after MI
      is about 25%. TWA is related to age and LV function but not to other common
      arrhythmia markers. Although TWA does not appear to be related to excessive
      cardiac morbidity, evaluation of the prognostic significance of TWA requires
      further study.

PMID- 11449593
TI  - Myocardial injury during radiofrequency catheter ablation: comparison of focal
      and linear lesions.
AB  - The aim of study was to investigate the extent of myocardial injury incurred by
      creation of continuous RF current induced linear ablation lesions (LL; ablation
      of atrial fibrillation, right atrial procedure) in comparison to focal RF lesions
      (FL; AV node reentry tachycardia, WPW tachycardia). In 23 patients with LL (age
      51.3 +/- 11.2 years, 18 men, 5 women) and in 16 patients with FL (age 53.9 +/-
      5.1 years, 8 men and 8 women), levels of creatine kinase (CK), myoglobin (MG),
      CKMB mass (CKMB M), CKMB activity (CKMB A), and cardiac troponin T (cTnT) were
      determined before and 2, 4, 8, 24, and 48 hours after ablation. CKMB A was normal
      in 87% in LL and 100% in FL (< 6% of CK) with median maximum CK values of 214 (45
      1583) U/L in LL and 36 (29-212) U/L in FL. Peak values of all parameters were
      significantly higher in LL than in FL. The sensitivity of cTnT was 50% in FL and
      100% in LL. In FL MG, total CK, and CKMB M were abnormal in only 12.5% of cases
      while in LL MG and CKMB M were pathological in 100% and total CK was abnormal in
      91.3% of patients. The amount of energy and number of RF applications correlated
      with cTnT, MG, and CKMB M (P = 0.01). In conclusion, (1) long linear RF current
      lesions for ablation of atrial fibrillation are associated with significantly
      greater myocardial injury than focal ablations. (2) In focal lesions only cTnT
      provided a sensitivity of 50% in the detection of myocardial injury while in
      linear lesions cTnT, CKMBM, and CKMB M seemed suitable for detection of RF
      current induced myocardial damage with 100% sensitivity. All biochemical
      parameters do not differentiate patients with coronary ischemia up to 48 hours
      after an ablation. (3) Further investigations are necessary to determine if RF
      current linear lesions lead to impaired atrial contractility in cases of
      extensive tissue damage.

PMID- 11449594
TI  - Studies on the prevalence of complicated atrial arrhythmias, flutter, and
      fibrillation in patients with reciprocating supraventricular tachycardia before
      and after successful catheter ablation.
AB  - Atrial flutter and AF are complications in approximately 30% of cases of
      paroxysmal supraventricular tachycardia (PSVT)-indicated catheter ablation, and
      it is of interest to determine if therapeutic modification for PSVT would
      eliminate combined atrial tachyarrhythmia like atrial flutter and AF. The aim of
      this study was to determine the incidence and the risk of atrial tachyarrhythmias
      after catheter ablation of PSVT. A total of 152 patients (age range 12-74, mean
      41 +/- 17 years) with accessory pathway (n = 106) and/or dual atrioventricular
      nodal conduction (n = 46) were enrolled in a 2-year follow-up program after
      successful catheter ablation. Possible risks on clinical background (age, sex,
      PSVT duration, hemodynamic instability during attacks), premature atrial
      contraction (PACs) on Holter monitoring, echocardiographic left atrial size, and
      electrophysiological property (insertion site, conduction type, effective
      refractory period) were evaluated. Atrial flutter and AF were complications in 53
      (35%) of the subjects, who were elderly and had a longer PSVT history with a
      larger left atrial dimension and frequent PACs; however, the electrophysiological
      properties were similar. After a 2-year follow-up period 36 (24%) of the patients
      still exhibited PAC runs, including 13 (9%) with atrial flutter and AF, each one
      of whom were complicated with nonlethal cerebral thromboembolism and congestive
      heart failure. Multiplelogistic-regression analysis revealed that advanced age (>
      or = 41 years, P = 0.0152) and frequent PACs (> or = 1% of total daily QRS
      counts, P = 0.0426) on Holter monitoring are the risk factors of PAC runs and/or
      atrial flutter and AF. In conclusion, successful ablation for PSVT is thought to
      be beneficial for preventing atrial flutter and AF. However, careful follow-up to
      monitor for the recurrence and atrial flutter and AF related complications,
      especially in patients of solitary atrial flutter and AF without reciprocating
      tachycardia and with frequent PAC.

PMID- 11449595
TI  - Reversible impairment of left and right ventricular systolic and diastolic
      function during short-lasting atrial fibrillation in patients with an implantable
      atrial defibrillator: a tissue Doppler imaging study.
AB  - AF with a fast ventricular response may cause ventricular mechanical impairment,
      though whether short-lasting AF with satisfactory rate control may affect
      ventricular function is unknown. This study investigated if prompt cardioversion
      by an implantable atrial defibrillator (IAD) may prevent left (LV) and right
      ventricular (RV) systolic and diastolic dysfunction. Ten patients (mean age 61 +/
      9 years, 8 men) with paroxysmal AF without structural heart disease who received
      an IAD were studied by echocardiography and tissue Doppler imaging (TDI) for both
      ventricles. Measurements were made during baseline sinus rhythm and at 1-minute,
      20-minute, 4-hour, and 1-week postcardioversion of an episode of spontaneous AF.
      The occurrence of AF and the ventricular rate were monitored at 2-hour intervals
      by the device. There were 50 episodes of AF with a mean duration of 8.8 +/- 8.9
      days (2 hours to 37 days). There was no difference in M-mode measured LV
      fractional shortening and ejection fraction between baseline sinus rhythm and
      after cardioversion. However, the TDI derived myocardial systolic velocity (TDI
      S) was significantly lower at 1-minute postcardioversion and was normalized at 1
      week in both LVs (baseline: 5.7 +/- 1.8, 1 minute: 4.2 +/- 1.0, 20 minutes: 4.3
      +/- 0.9, 4 hours: 4.8 +/- 1.0, 1 week: 5.5 +/- 1.8 cm/s; P < 0.005 when comparing
      1 minute and 20 minutes to baseline; P < 0.05 when comparing 4 hour to baseline)
      and RV (baseline: 10.4 +/- 2.1, 1 minute: 7.8 +/- 1.4, 20 minutes: 8.1 +/- 1.2, 4
      hours: 9.2 +/- 1.5, 1 week: 10.0 +/- 2.0 cm/s; P < 0.005 when comparing 1 minute,
      20 minutes, and 4 hours to baseline). For diastolic function, transmitral Doppler
      study showed a decrease in early filling velocity at 1 minute (P < 0.05) and 20
      minutes (P < 0.005), which was normalized at 4 hours. There was no change in
      transtricuspid Doppler flow. However, TDI derived myocardial early filling
      velocity was decreased in the LV (baseline: 6.0 +/- 2.8, 1 minute: 5.4 +/- 2.3,
      20 minutes: 5.4 +/- 2.1, 4 hours: 6.1 +/- 2.2, 1 week: 5.8 +/- 1.7 cm/s; P < 0.05
      when comparing 1 minute and 20 minutes to baseline) and RV (baseline: 8.9 +/-
      3.5, 1 minute: 7.9 +/- 3.3, 20 minutes: 8.1 +/- 3.3, 4 hours: 8.5 +/- 2.9, 1
      week: 8.4 +/- 3.5 cm/s; P < 0.05 when comparing 1 minute to baseline). AF of a
      longer duration (> 48 hours) resulted in a more depressed TDI-S in LV (> 48
      hours: 4.2 +/- 1.0, < or = 48 hours: 5.3 +/- 1.3 cm/s; P < 0.01). Shocks in sinus
      rhythm did not affect any of the above echocardiographic parameters. Therefore,
      despite adequate rate control, short-lasting AF impairs systolic and diastolic
      function in both ventricles, which improves gradually after cardioversion. Early
      restoration of sinus rhythm by an IAD minimizes ventricular dysfunction. TDI is a
      sensitive tool to assess early systolic and diastolic dysfunction.

PMID- 11449596
TI  - Correlation of impedance minute ventilation with measured minute ventilation in a
      rate responsive pacemaker.
AB  - Although rate responsive pacing based on impedance minute ventilation (IMV) is
      now standard, there is almost no data confirming the relationship between IMV
      from an implanted pacemaker and measured minute ventilation (VE) during exercise.
      Nineteen completely paced adults implanted with Medtronic Kappa 400 pacemakers
      underwent symptom-limited maximal metabolic treadmill testing using a modified
      Minnesota Pacemaker Response Protocol. Minute ventilation (VE, L/min) was
      simultaneously measured using the flowmeter of a respiratory metabolic gas
      analysis system and the transthoracic impedance minute ventilation circuitry of
      the pacemaker. Correlation coefficients (r) were used to find the best fit line
      to describe the relationship between the two measurements. Mean (+/- SD) r values
      for the first, second, and third order polynomial equations and for log and
      exponential equations were: 0.92 +/- 0.08, 0.94 +/- 0.04, 0.95 +/- 0.04, 0.91 +/-
      0.06, and 0.91 +/- 0.07, respectively. None of the r values were statistically
      different from the first order equation. Transthoracic IMV as measured by the
      Medtronic Kappa 400 is closely correlated to measured minute ventilation and is
      represented well by a first order (linear) equation.

PMID- 11449597
TI  - Clinical evaluation of morphology discrimination: an algorithm for rhythm
      discrimination in cardioverter defibrillators.
AB  - The aim of this study was to test the new morphology discrimination diagnostic
      algorithm for ICDs that differentiates supraventricular tachycardias (SVTs) from
      VTs by analysis of ventricular depolarization complexes morphology. Twenty-five
      patients implanted with a St. Jude Ventritex single chamber ICD were studied
      during electrophysiological evaluation at predischarge and were followed for 7 +/
      4 months. Sensitivity and specificity for VT detection and overall diagnostic
      accuracy of the morphology discrimination algorithm were calculated on 326
      detected events. At electrophysiological evaluation, the algorithm was tested
      during 67 episodes of right atrial pacing, during 119 episodes of RV pacing (at
      basal interventricular septum and RV apex) and during 27 episodes of sustained
      AF: specificity was 98%, sensitivity was 66%, and diagnostic accuracy was 80%.
      All episodes of AF were correctly diagnosed as SVT. Exclusion of detections
      related to pacing at the basal interventricular septum, resulted in a specificity
      of 98%, a sensitivity of 85%, and a diagnostic accuracy of 93%. During follow-up,
      evaluation of the morphology discrimination algorithm on 113 spontaneous episodes
      (31 VTs, 31 AF, 7 SVTs, and 44 sinus tachycardias) exhibited a specificity of
      89%, a sensitivity of 100%, and a diagnostic accuracy of 92%. In conclusion, the
      morphology discrimination algorithm exhibits a high specificity in discriminating
      VTs from SVTs, although with a corresponding reduction in sensitivity. The
      preliminary experience on spontaneous episodes is promising. To correct for the
      reduction in sensitivity, it is advisable to use this algorithm in parallel with
      other algorithms for rhythm discrimination (sudden onset, stability) coupled with
      extended high rate.

PMID- 11449598
TI  - Direct thrombin inhibitors: are they the future of anticoagulation?

PMID- 11449599
TI  - Medical education through community experience: community projects at the
      University of South Dakota School of Medicine.
AB  - Community projects are a requirement of third-year medical students at three
      South Dakota clinical campuses. Students identify a community issue, design and
      implement either a service or research project, and present the project to
      faculty and peers. Topics include cardiovascular and other disease risk factors,
      nutrition education, firearm safety and many others. These projects answer a need
      to advance an understanding of population health, promote community involvement
      among student physicians, and improve the health of the community.

PMID- 11449601
TI  - The white coat.

PMID- 11449600
TI  - Congenital aortic insufficiency with coronary ostial occlusion: a case report.

PMID- 11449602
TI  - Kentucky Board of Medical Licensure.

PMID- 11449603
TI  - Slip, slop, slap, and wrap.

PMID- 11449604
TI  - [Pollen count and allergic sensitization against early pollinators in children in
      Munich and Dresden].

PMID- 11449605
TI  - [Immunomicroscopic identification of major allergens in pollen of cat's tail
      grass (Phleum pratense L.)].

PMID- 11449606
TI  - [Quality control surveys by the Foundation of the German Pollen Report Service].

PMID- 11449607
TI  - [Geographic and time trends of pollen count due to beeches, grass and mugwort
      (Artemisia) in Germany].

PMID- 11449608
TI  - [Preventive monotherapy with montelukast versus DNCG in children with mild
      asthma. Results of and exploratory pilot study].
AB  - BACKGROUND: Montelukast is used as an add-on medication with inhaled steroids in
      the therapy of childhood asthma. The aim was to determine the clinical effect of
      montelukast as a prophylactic therapy in mild asthma in comparison with inhaled
      sodium cromoglycate. METHOD: 20 children aged 6-14 years were treated in a 20
      week open-labelled randomized cross-over design, starting after a 2-week run-in
      period with either montelukast or cromolyn for 16 weeks with a 2-week wash-out
      period between treatments. RESULTS: Children treated with cromoglycate showed a
      significant increase of FEV1 (100.6 vs. 96.5%, p < 0.01) and MEF25 (70.6 vs.
      59.1%, p < 0.05) in base line lung function and after cold air challenge (FEV1
      97.2 vs. 91.2%, p < 0.05; MEF25 62.9 vs. 54.4%, p < 0.01). Treatment with
      montelukast effected a significant increase (p < 0.05) in MEF25 from 59.1 to
      67.8% in base line lung function alone. Both medications resulted in significant
      decreases (p < 0.05) in daytime asthma symptoms and evening peak flow
      variability. Comparing the two treatment substances no statistically significant
      differences could be registered in any endpoints including beta-agonist use.
      CONCLUSIONS: Both cromolyn and montelukast showed effective control of mild
      asthma in children; however, montelukast is more convenient in its application.
      Further studies are needed to determine the role of leukotriene receptor
      antagonists in childhood asthma.

PMID- 11449609
TI  - [Non-tubercular mycobacterial infection of the lungs due to Mycobacterium
      smegmatis].
AB  - Nontuberculous mycobacteriosis due to M. smegmatis is a rarity. We report on the
      case of a 51 year old male HIV-seronegative patient without predisposing
      bronchopulmonary disease, but with a state after gastrectomy and splenectomy who
      developed unproductive cough, night sweat and weight loss. The chest radiograph
      and thoracic CT showed wide-spread bilateral patchy infiltrations. Histological
      examination of transbronchial biopsies revealed chronic carnificating pneumonia.
      A perhoracic fine-needle biopsy showed caseating epitheloid cell granulomas with
      acid fast bacilli. These were identified as M. smegmatis by PCR with subsequent
      sequencing. Acid fast bacilli could not be detected microscopically neither in
      sputum nor in bronchial secretions, however M. smegmatis has been repeatedly
      detected by culture in these materials. In neither material tubercle bacilli have
      been detected by nucleic acid amplification (NAT) or culture. Immunologic
      investigations revealed a reduced number of CD4+ lymphocytes and a reduction of
      interferon alpha- and -gamma-synthesis by peripheral blood mononuclear cells.
      Treatment with Rifabutin, Ethambutol, Clarithromycin and Ofloxacin resulted in
      complete clinical and roentgenological resolution.

PMID- 11449610
TI  - [Stabilization of two patients with brittle asthma by inhaled beclomethasone
      dipropionate with small particle size].
AB  - Two patients with brittle asthma whose bronchial obstruction was less variable
      during treatment with HFA-beclomethasone (HFA-BDP) solution aerosol than with
      other previous treatments are presented here. In order to evaluate whether this
      improvement was related to the smaller particle size of the new formulation (MMAD
      1.1 mu vs 4 mu with the CFC-formulation) both patients participated in a
      prospective case study sequence. METHOD: During a 4 week run-in both patients
      inhaled 200 micrograms of HFA-BDP (Ventolair) BID from the Autohaler followed by
      4 weeks of treatment with 500 micrograms CFC-BDP (Aerobec) BID from the Autohaler
      in study phase 1 and 4 weeks of treatment with 200 mcg HFA-BDP (Ventolair) BID
      from the Autohaler in study phase 2. During the entire study period other
      concomitant medications remained unchanged. The dose of CFC-BDP was chosen to be
      2.5 times higher than the HFA-BDP dose to get approximately comparable amounts of
      intrabronchial deposition. During the study Peak-Flow and concomitant medications
      were recorded daily. RESULTS: Both patients showed significantly higher Peak-flow
      values during treatment with Ventolair (HFA-BDP) than during treatment with
      AeroBec (CFC-BDP). P-values were p < 0.0001 and p < 0.005 for patient 1 and 2
      respectively. CONCLUSION: At a comparable intrabronchial dose these two cases of
      brittle asthma showed significant improvements in control of bronchial
      obstruction with a BDP-formulation of smaller particle size. This is an indicator
      that smaller airways in the periphery of the lung participate in the inflammatory
      process leading to bronchial obstruction and that deposition of inhaled steroids
      in this region could have therapeutic advantages.

PMID- 11449611
TI  - [Eosinophilic bronchitis without asthma--an additional rare cause for chronic
      persistent cough (CPC)? A 30-year old patient with severe CPC due to eosinophilic
      bronchitis without asthma or hyperreactivity].
AB  - In non-smokers the underlying causes for chronic persistent cough (CPC) e.g.
      chronic cough without diagnostic chest X-ray or pulmonary function test--are
      usually as follows: several common upper airways diseases, bronchial (cough type)
      asthma, gastrooesophageal reflux or treatment with an ACE (angiotensin converting
      enzyme)--inhibitor. In 10% of CPC however the cause remains uncertain. We report
      a 30 year old non-smoker with severe coughing and repeated vomiting for two
      months. No laboratory or technical data could be collected suggestive of a common
      cause of CPC: Upper airways disease, bronchial flow limitation or
      hyperresponsiveness, ACE inhibitor medication, B. pertussis infection,
      gastrooesophageal reflux disease (by 24 hours pH-probe) were ruled out.
      Fiberbronchoscopic findings remained unremarkable, except for the bronchial
      biopsy specimen, which showed moderate eosinophilic inflammation of the mucosa
      and marked thickening of the subepithelial layer. Since the cough was non
      productive, sputum induction with 3 ml nebulised 3% NaCl solution was performed.
      28% of the granulocytes were eosinophil stained. A low quality morning sputum (<
      1 ml) showed 21% eosinophilia. Thus, the diagnosis of eosinophilic bronchitis was
      established. 400 micrograms budesonide dry powder inhalations b.i.d. for one week
      resolved the cough, treatment was stopped after three weeks. No recurrence was
      seen two months later. Both the cough type asthma and the eosinophilic bronchitis
      could represent a form fruste of classical bronchial asthma beyond wheezing or
      dyspnoea, but with the common main symptom: cough. Since hyperresponsiveness and
      cough are phenotypic hallmarks of cough variant asthma, in eosinophilic
      bronchitis--beside cough--another two features of asthma are present:
      eosinophilic inflammation of the mucosa along with sputum eosinophilia and
      subepithelial layer thickening. Not surprisingly, eosinophilic bronchial
      inflammation could be shown in patients with cough variant asthma as well, who-
      up to 56% during a four year-period--develop classic asthma. The long-term
      outcome of eosinophilic bronchitis is not known, however. Thus, asthma, cough
      variant asthma and cough due to eosinophilic bronchitis can mirror different
      phenotypes or phases of the same entity. CPC due to either the cough type asthma
      or the eosinophilic bronchitis is like asthma fast responding to inhalative
      steroids. (Induced) sputum staining should be added to the diagnostic
      armamentarium of CPC.

PMID- 11449612
TI  - [Treatment of bronchial asthma using a new adjustable combination treatment plan:
      Asthma Control Plan (ATACO)].
AB  - The current guideline of the German Respiratory League (Deutsche Atemwegsliga)
      recommends the synergistic combination therapy with long acting beta 2-agonists
      and inhalative corticosteroids only for patients suffering from moderate to
      severe persistent asthma (step 3 and 4 of the asthma severity scale). Now
      convenient fixed combinations of these substances are available, which could
      enhance patient's compliance. A large, randomised, parallel-group study in 8000
      mild to moderate asthmatics was designed to compare a flexible asthma control
      plan with the conventional fixed-dose management with respect to quality of life,
      symptom control and treatment costs. The fixed combination of 6 micrograms
      Formoterol and 200 micrograms Budesonide per puff in a new dry powder device was
      applied either due to a novel flexible asthma control plan "ATACO" (group A) or
      as a standardised conventional dosing regimen (group B) inhaling two puffs b.i.d.
      In group A (ATACO) patients reduce the run-in dose after four weeks from two
      puffs b.i.d. to one puff b.i.d. with the option of doubling the dose immediately,
      if (pre-defined) asthma deterioration occurs. One week later the dose can be
      either doubled again or reduced due to the actual asthma symptoms of the patient.
      After run-in, group B patients continue to take two inhalations b.i.d. In this
      group, asthma exacerbations will be managed as usual by the physician. In
      contrast, the ATACO group flexible management plan allows the self-medication: an
      immediate increase in the dose of the fixed combination will lead to both a fast
      relief of bronchospasm and an automatically higher dosed corticosteroid treatment
      for the underlying asthmatic inflammation. Conversely, if later asthma symptoms
      improve, less reliever and controller medication will be needed and used. The
      immediate treatment of new onset bronchospasm and asthmatic inflammation by the
      patient himself could maintain at least the same grade of asthma control, as the
      conventional group B treatment, improve asthma-related quality of life and
      decrease treatment costs. If the concept works, fixed combinations of long-acting
      beta 2 agonists and inhalative corticosteroids could have an impact on future
      asthma guidelines.

PMID- 11449613
TI  - [T-cell receptor and allergy--a survey].

PMID- 11449614
TI  - [Automated quantitative image cytometry of bronchial washes in possible
      bronchopulmonary tumors: comparison with cytology, histology and clinical
      diagnosis. Pneumology 1999; 53(12): 583-9].

PMID- 11449615
TI  - [Operative standard therapy of micro- and macro-invasive carcinoma of the
      cervix].
AB  - Radical hysterectomy with bilateral lymphonodectomy represents one of the most
      important strategies in the treatment of cervical cancer, especially in early
      stage disease with small tumor volume. Nowadays, 5-year survival rates of
      patients with stage IB and IIA range between 87% and 92%. Ovary preserving
      management in cervical cancer is justified in early stage disease and younger
      women (< 45 years), and regarded as standard treatment. Therapy of microinvasive
      cervical cancer (Stage Ia1 und Ia2) depends on depth of invasion, superficial
      spread of lesion, and other prognostic criteria. Exact work-up of the cone is the
      basis for successful treatment. A great variety exists in regard to radicality of
      surgery in patients with cervical cancer--ranging between modified radical
      hysterectomy and radical hysterectomy with resection of the parametria to both
      pelvic side walls. Assessment of lymph node status is mandatory for individual
      treatment. Pelvic lymphonodectomy represents standard treatment at radical
      hysterectomy, and if positive, paraaortic lymphonodectomy is indicated.
      Micturition disorders, urinary incontinence, lymph cysts, bowel problems,
      thrombophlebitis, urogenital fistulas, and pulmonary embolism are the most
      frequent complications following radical hysterectomy. Today, there is an
      increasing competition between different therapy strategies in cervical cancer
      such as primary irradiation, chemoradiation, neoadjuvant chemotherapy,
      laparoscopic radical hysterectomy, vaginal radical hysterectomy combined with
      laparoscopic surgical staging. All these treatment modalities have to be compared
      with the "golden standard" comprising survival and recurrence rates functional
      results, morbidity, mortality and quality of life.

PMID- 11449616
TI  - [Total mesometrial resection: nerve-sparing extended radical abdominal
      hysterectomy].
AB  - The total mesometrial resection (TMMR) is the first radical hysterectomy
      procedure based on defined anatomical landmarks with all surgical steps. The new
      abdominal operation combines maximum resection of the oncologically relevant
      mesometrium with minimal tissue traumatization and sparing of the pelvic
      autonomic nervous system. The extended pelvic and low periaortic lymph node
      dissection which is part of the procedure includes the removal of the lymphatic
      tissue localized laterally and dorsally of the main vessels. A prospective
      multidimensional trial is currently under way to evaluate the potential of the
      total mesometrial resection to improve the therapeutic index in the surgical
      treatment of carcinoma of the uterine cervix, especially for high risk tumors.

PMID- 11449617
TI  - [New concepts for staging and therapy of cervix cancer by endoscopic surgery].
AB  - Non-invasive staging of cervical cancer according to FIGO is out-dated. In
      contrast to clinical staging exact histopathologic evaluation of tumor extension
      and tumor biology can be achieved via laparoscopic evaluation. Invasive
      endoscopic staging is advantageous and should be integrated into the diagnostic
      armamentarium of gynecologic oncologists and radiotherapists. Through
      magnification and blood-less surgery minute anatomical structures can be
      identified laparoscopically. Thus, fibers of autonomic nerves can be visualized
      and parasympathetic fibres can be preserved. Conservation of these neural
      structures leads to significant reduction of postoperative morbidity of bladder
      and rectum. The concept of the sentinel lymph node is also valid for the uterine
      cervix. Selected biopsy of the sentinel node and identification of single tumor
      cells leads potentially to higher oncologic safety and may reduce morbidity
      associated with radical lymphadenectomy. In early stage cervical cancer fertility
      may be preserved by radical trachelectomy which is combined with laparoscopic
      parametric and pelvic lymphadenectomy. Following radical trachelectomy a
      pregnancy rate of 40% is achieved, the recurrence rate following conventional
      radical hysterectomy is identical.

PMID- 11449618
TI  - [Pathologic-anatomic description and basic morphological information for
      management of dysplasias and carcinomas of the cervix uteri].
AB  - Histopathology is the bedrock and cornerstone in the management of malignant
      tumors. Careful macroscopic description with selection of representative tissue
      for histologic examination is required for quality assurance and quality
      improvement and for assessing prognostic factors in cervical cancer specimens.
      The pathology report in cervical cancer (CX) should include three-dimensional
      tumor measurement, the exact measurement of depth of infiltration of the cervical
      wall, tumor grading, the presence of lymphatic space as well as blood vessel
      involvement. The statement for resection margins should include the vaginal,
      parametrane, rectal and vesical direction. All resected lymph node should be
      counted, measured and processed completely in step sections. If lymph node
      metastases are diagnosed, the report should include the size and count of
      metastatic nodes in relation to resected nodes. Pelvic and para-aortal nodes
      should be reported separately. Lymph nodes in the parametrane tissue represent
      regional nodes; and metastatic involvement should be stated as pN1 and not as
      pT2b. The tumor typing and staging should be conform with WHO-classification of
      malignant tumors and the TNM-classification system. The last one should be used
      in all cases which were surgically treated. Konizations and LOOP-excision
      specimens should be processed completely in step sections. The pathology report
      must include the severity of CIN-lesion, changes caused by HPV-infection,
      according to colposcopic localisation.

PMID- 11449619
TI  - [Histopathological prognostic factors in primary surgically treated cervix
      carcinoma].
AB  - OBJECTIVE: Standardised morphologic evaluation of radical hysterectomy specimens
      in primary surgically treated cervical cancer improves the selection of cases for
      adjuvant therapy and the precision for prognosis and may be helpful in quality
      control of oncologic surgery. MATERIAL AND METHODS: Following standardised
      macroscopic evaluation [29] the original histologic slides of all surgically
      treated patients with cervical cancer were searched for tumor type,
      histologically proven pelvic lymph node metastases (PLM), lympho-vascular space
      involvement (LVSI), tumor differentiation (grading), peritumoral inflammatory
      response, pattern of cervical wall involvement and relative depth of invasion.
      The results were compared with follow up. RESULTS: The frequency of patients up
      to 35th year of age was 28.8% and increased between 1979 and 1993 of about 10% (p
      > 0.05). Younger women represented more pT1 b1-tumors (55.6% vs. 47%), but
      without statistic significance. Contrary to advanced tumor stage and the presence
      of PLM, adenocarcinomatous histology (5.1% of all cases) was not associated with
      poor prognosis. Patients with pT1b-tumors of more than 4 cm largest extension
      (pT1 b2) showed a twice-fold frequency of PLM and pelvic recurrences. Five-year
      survival rate (5-Y-SR) decreased (82.7% vs. 64.9%) and more patients died of
      cancer (p = 0.005, each). Diffuse infiltration pattern was accompanied with
      higher rate of tumor recurrency and a shortening of 5-Y-SR compared with pushing
      borders at the front of infiltration, 38% versus 13.7% and 45.4% versus 75.2%,
      respectively. Similar was seen in poorly differentiated tumors (G3), compared
      with well differentiated (G1) carcinomas (recurrency: 15.1% vs. 27.5%, 5-Y-SR
      75.7% vs. 59.3%; p < 0.05). Cases with the presence of LVSI, absence of
      peritumoral inflammatory response and deep cervical infiltration (> 66%) were
      accompanied with poor prognostic outcome. CONCLUSIONS: In patients with primary
      surgically treated cervical cancer prognostic risk evaluation can be made by
      standardised histopathologic handling of hysterectomy specimens. Cases with early
      cervical cancer and high tumor load (pT1 b2), advanced staged disease (pT2 b),
      histologically proven PLM, LVSI, poor tumor differentiation (G3), absence of
      peritumoral inflammatory response and deep cervical wall infiltration are
      associated with poor prognostic outcome. Patients with these morphologic
      patterns, which can be established by clinical examination and diagnostic biopsy,
      represent the clientel for adjuvant or neoadjuvant therapy.

PMID- 11449620
TI  - [Survival tree analysis--a new method for multivariate evaluation of prognostic
      factors in operative cervix carcinoma].
AB  - OBJECTIVE: We introduce a new multivariate analysis, not yet applied to
      gynecologic cancer, that includes the creation of a survival tree. The tree
      structured survival analysis is a statistical method designed to identify
      meaningful prognostic subsets in a study population, which usually do not emerge
      from routine proportional hazards analysis. We also applied the scoring systems
      from other groups to our patients and compared them with our system using a
      variety of statistical methods. MATERIAL AND METHODS: After excluding patients
      with microinvasive and small cell carcinoma, data from remaining 301 patients
      were analyzed. We performed an univariate and multivariate analysis. Significant
      single parameters and other variables considered important were chosen for
      multivariate analysis, including the creation of a survival tree. RESULTS: Risk
      factors to define prognosis best were: Depth of invasion, lymph vascular space
      involvement, age of 40 years and lymph node metastases. CONCLUSIONS: The
      presented model separates patients with early stage invasive carcinoma of the
      cervix into three subgroups with a significant different survival and correlates
      well with other models. Our new model is easy to apply and only requires depth of
      invasion, lymph vascular space involvement, node status and age of a patient to
      define the individual risk.

PMID- 11449621
TI  - [Adjuvant radio- and chemotherapy in cervix carcinoma].
AB  - The screening for cervical cancer has been reduced both the incidence of and
      mortality from invasive cervical cancer in the western world. Radical pelvic
      surgery is an effective treatment for early invasive cervical cancer (FIGO-stage
      IB and IIA), but for woman with more advanced disease radiotherapy is the
      standard treatment. However, the survival of the cervical cancer patients has not
      been improved over the last decade. Previous studies have suggested that
      chemotherapy and radiotherapy are synergistic. The results of five large studies
      have shown that cisplatin-based chemotherapy when given at the same time a
      radiation therapy, prolongs survival in woman with cervical cancer. This was also
      observed in primary treatment schedule as in adjuvant situation. The side effects
      were temporary and manageable. The results suggest that chemoradiation is the
      favorable therapy for cervical cancer in advanced stage and in high-risk
      situation.

PMID- 11449623
TI  - [Possibilities of vaccination against HPV infections in cervix carcinoma].
AB  - According to epidemiologic and clinical observations as well as from animal
      experiments it is expected that prevention of cervical cancer based upon an HPV
      specific immunization can be achieved by prophylactic vaccination (induction of
      neutralizing antibodies) or by immune therapy (induction of cytotoxic T cells in
      women with CIN). Immune therapy of already existing tumors is most likely only
      possible as an adjuvant treatment. Virus-like particles (VLP) are currently being
      developed as prophylactic vaccine that can be obtained by expression of the L1
      protein. The viral oncoproteins E6 and E7 are prime candidates for therapeutic
      vaccines administered either as purified molecules or carried by recombinant
      vectors such as vaccinia virus. Initial clinical trials with the HPV types which
      are most prevalent in cervical cancer exhibited promising results, yet next
      generation vaccines are already under development.

PMID- 11449622
TI  - [Adjuvant chemotherapy of cervix carcinoma--results of a phase II study].
AB  - OBJECTIVE: Therapies involving a radical operation and radiation treatment for
      cervical carcinoma in stages I and II are not sufficiently effective in patient
      subgroups with high risk for recurrence. In recent publications, patients with
      high risk cervical cancer had with adjuvant simultaneous radio-chemotherapy a
      better disease free and overall survival but a higher toxicity compared with
      patients received an adjuvant radiotherapy alone. MATERIAL AND METHODS: 34
      patients with at least 2 risk factors for recurrence of cervical cancer were
      treated with adjuvant chemotherapy after radical hysterectomy. The protocol
      consisted of 3 cycles of ifosfamide 1.6 g/m2 (d 1-3) and carboplatin (AUC 4, d1)
      every three weeks. For cell protection 21 patients received amifostine 740 mg/m2
      d1-3; this was followed by standard radiation therapy (50.4 Gy percutaneous and
      high-dose-rate-after-loading for 21 patients, 2 x 5 Gy). The dose determination
      of the substances and their toxicity were investigated. RESULTS: Patient (p)
      data: Median age 43 years (range: 25-70); pT1b-2a: n = 22; pT2b: n = 12; pN1: n =
      28; pN0: n = 6; G3: n = 10; adeno- and adenosquamous carcinoma: n = 9, G3: n =
      10, R1-resection: n = 5. 70.6% of these high-risk patients were disease-free
      after a median observation time of 40 (18-62) months. Median number of cycles of
      chemotherapy: 2.8. There was no more dose escalation than carboplatin according
      to AUC 4 possible. Hematologic toxicity (CTC grading, % of 96 documented cycles):
      anemia-grade 3-4: 30; -grade 1-2: 10.4; leukopenia-grade 3-4: 13, -grade 1-2:
      21.7; alopecia-grade 3: all p.; cerebral neurotoxicity-grade 3-4: 8.3, -grade 1
      2; 17.7; diarrhea under radiotherapy-grade 3-4: 2 p., -grade 1-2: 6 p.
      CONCLUSION: This combined sequential adjuvant therapy was effective and had an
      acceptable level of toxicity. A phase III study comparing adjuvant sequential
      chemo-radiotherapy with and without Erythropoeitin to counteract the negative
      effects of anemia started in Germany in 1999 and had randomized now about 270
      patients.

PMID- 11449624
TI  - [Significance of family anamnesis in cervix carcinoma].
AB  - OBJECTIVE: Except for certain types of familiar cancer, the impact and
      contribution of familial factors to the development of sporadic cancer is thought
      to be relatively minor. Some earlier case reports had been suspected genetic
      background in cervical cancer (CX). MATERIAL AND METHODS: The literature was
      screened and cervical cancer patients from the Department of Obstetrics and
      Gynecology of the University Hospital of Leipzig were searched for familiar
      history of malignant tumors at any sites to establish familial risk for CX.
      RESULTS: Analysis showed, that 15 to 20% of cervical cancer represented at least
      one first-degree relative with malignant disease any site. The familial relative
      risk for in situ or invasive CX was reported to range between 1.8 to 2.0 and the
      heretability was between 0.11 and 0.15 for in situ and 0.22 and 0.33 for the
      invasive form. In some families a clustering, i.e. two or more female first
      degree sibs were affected by CX, was observed, the frequency ranged between 1.7
      and 7%. Analyses of risk by age of onset are rarely done and the results are
      controversy. Two large studies reported an aggregation of tobacco-related and HPV
      associated malignancies, like oro-pharyngeal, lung and anorectal sites, in
      cervical cancer families. Moreover, it has been shown, that both mothers and
      daughters, who had invasive CX as the first primary cancer, had an excess of lung
      cancer as a second tumor site. CONCLUSIONS: The correlation of HPV-associated
      neoplasms in affected families suggest a role of mild or moderate hereditary
      immunosuppression in explaining a part of familial predisposition to cervical
      cancer are biologically founded. Consequently, this would not imply germ line
      mutations in oncogenes or tumor suppressor genes but in genes modulating immune
      response and perhaps causing susceptibility to a variety of viral infections.

PMID- 11449625
TI  - [Cancer register for cervix carcinoma--useful and necessary?].
AB  - During the last two decades, cancer research has shifted from using cell lines
      and animal models to using methods and models that use human tissues from defined
      tumors. DNA and RNA can be analysed from fresh tissue from samples obtained at
      surgery, biopsy, cytologies or necropsy as well as from paraffin-embedded
      material. Archival material has several advantages: not only it is from
      individuals for whom disease process has been documented, but also data may
      available about the outcome as well as the response to treatment. Material
      available from well-controlled clinical trails would enable a wide range of
      hypotheses to be tested. Laser microdissection allows to sample cellular material
      from histopathologic well documented areas of the tumor, including special
      differentiated areas. It is necessary to establish tumor registries, especially
      in gynecologic oncology to get material from well described tumors for molecular
      profiling, the molecular analysis of clonality in tumors and malignant
      progression. At the Leipzig University a cervical tumor registry has been
      established in March 1979. Until the end of December of the year 2000 1,030 cases
      of surgically treated cervical cancer from stage pT1b1 up to pT2b including
      paraffin blocks and original histologic slides were collected. First evaluation
      up to the end of 1996 (n = 919) has shown, that 27.2% of the patients represented
      with histological proven pelvic lymph node metastases. The majority of cases were
      staged pT1b1 (52.1%), followed by stage pT2b (23.9%), pT1b2 (9.7%) and pT2a
      (9.5%). In 44 cases stage was not documented. In about 95.2% datas about the
      follow up of the patients were available. In conclusion, tumor registries are
      helpful in establishing and controlling uniform criteria for the accurate
      determination of prognostic factors and exact histopathologic evaluation can
      ideally be combined with new tools in molecular pathology, i.e. histopathology
      meets genomics.

PMID- 11449626
TI  - [Therapy with monoclonal antibodies].

PMID- 11449627
TI  - [Monoclonal antibodies: development and clinical prospects].

PMID- 11449628
TI  - [Clinical use of monoclonal antibodies in malignant lymphomas].

PMID- 11449629
TI  - [Development and use of anti-epithelial antibodies in solid tumors].

PMID- 11449630
TI  - [Trastuzumab, a new treatment approach in breast carcinoma].

PMID- 11449631
TI  - [New approaches to treatment in immunology with monoclonal antibodies].

PMID- 11449632
TI  - [Bispecific antibodies in hematology and oncology].

PMID- 11449633
TI  - [Radioimmunoconjugates: therapy of non-Hodgkin lymphomas and colorectal
      carcinomas].

PMID- 11449634
TI  - [Tumor vaccination using monoclonal antibodies].

PMID- 11449635
TI  - [Suicidal crises and intervention in internal medicine].

PMID- 11449636
TI  - [Reversible grade III atrioventricular block in a 35-year-old patient].

PMID- 11449637
TI  - [44-year-old patient with thrombocytopenia, multiple organ failure and
      disseminated intravascular coagulation caused by drug poisoning with paracetamol,
      metamizole, benzodiazepines and alcohol in attempted suicide].

PMID- 11449638
TI  - [Changes in therapy of resectable rectal carcinoma].

PMID- 11449639
TI  - [Antiviral therapy of chronic viral hepatitis].

PMID- 11449640
TI  - From moulds to drugs.

PMID- 11449641
TI  - The future of antibiotics: facing antibiotic resistance.

PMID- 11449642
TI  - Perfecting the ring and extending the antibacterial spectrum: 'the multiple
      generations'.

PMID- 11449644
TI  - Crossing the envelope: how cephalosporins reach their targets.

PMID- 11449645
TI  - Cooperative evolution of mechanisms of beta-lactam resistance.

PMID- 11449646
TI  - Homage from one Sardinian to another.

PMID- 11449647
TI  - The final goal: penicillin-binding proteins and the target of cephalosporins.

PMID- 11449648
TI  - Cephalosporins: a microbiological update.

PMID- 11449649
TI  - Pharmacokinetics of antibiotics with special emphasis on cephalosporins.

PMID- 11449650
TI  - Cephalosporins: a pharmacological update.

PMID- 11449651
TI  - The pharmacokinetics of oral cephalosporins.

PMID- 11449652
TI  - The role of oral cephalosporins in ambulatory medicine.

PMID- 11449653
TI  - Perspectives of oral cephalosporins in upper respiratory tract infections.

PMID- 11449654
TI  - Oral cephalosporins in pharyngotonsillitis: is it necessary to use an antibiotic
      with activity against Haemophilus influenzae?

PMID- 11449655
TI  - Giuseppe Brotzu and the discovery of cephalosporins.

PMID- 11449656
TI  - Oral cephalosporins in the treatment of acute otitis media.

PMID- 11449657
TI  - The new oral cephalosporins in community-acquired infections.

PMID- 11449658
TI  - Oral cephalosporins in airway infections.

PMID- 11449659
TI  - Oral cephalosporins in uncomplicated urinary tract infections.

PMID- 11449660
TI  - New oral cephalosporins in pediatric community-acquired infections.

PMID- 11449661
TI  - Overview of cefixime use in community-acquired infections.

PMID- 11449662
TI  - Affinities of cephalosporins for penicillin-binding proteins and their
      antibacterial activities in the presence of human serum albumin.

PMID- 11449663
TI  - Role of parenteral cephalosporins in community-acquired lower respiratory tract
      infections.

PMID- 11449664
TI  - Role of long-acting cephalosporins in the treatment of lower respiratory tract
      infections.

PMID- 11449665
TI  - Application of pharmacoeconomics to the use of antibiotics.

PMID- 11449666
TI  - The astonishing complexity of antibiotic resistance.

PMID- 11449667
TI  - Antibiotic resistance in hospital infections: the role of newer cephalosporins.

PMID- 11449668
TI  - Strategies for antibiotic selection in empirical therapy.

PMID- 11449669
TI  - Gene therapy.
AB  - With recent advances in molecular biology, the ability to transfer genes to
      patients is becoming a reality. Ongoing clinical trials using gene transfer
      techniques have illustrated the potential and pitfalls of this new therapeutic
      modality for the treatment of a wide variety of disorders. While these techniques
      are not currently a part of routine clinical practice, it is only a matter of
      time until some form of gene therapy is approved for general use in the clinic.
      This review highlights some of the basic methods used in current gene therapy
      protocols. The objective of this review is to familiarize practitioners with
      these concepts so they can more effectively follow the progress of this emerging
      technology and better inform their patients.

PMID- 11449670
TI  - Effect of biflavones of Ginkgo biloba against UVB-induced cytotoxicity in vitro.
AB  - The effect of Ginkgo biloba extract on Ultraviolet B (UVB) irradiated fibroblasts
      was examined by using a neutral red dye uptake assay and a lactic dehydrogenase
      (LDH) release assay. Crude extract along with individual components, including
      flavone-glycosides and biflavones, were applied to cultured normal human skin
      fibroblasts for 12 hours, and 0, 20, 40 and 80 mJ/cm2 of UVB were irradiated. Two
      synthetic flavonoids, quercetin and rutin, which have polyphenol structures close
      to the flavonoids in Ginkgo biloba extract, were used to compare any structure
      related activity under the same conditions. At the concentrations (from 0.25 to 2
      mg/ml) treated with biflavone components (isoginkgetin/ginkgetin, sciadopitysin)
      and quercetin, high neutral red dye uptake was detected with gradual increases in
      UVB irradiation. The time-course release of LDH was determined as the
      cytotoxicity index (%) during 24 hours following a high dose UVB irradiation (200
      mJ/cm2), and the pattern of this cytotoxicity index was similar to that of the
      neutral red dye uptake results. Sciadopitysin, isoginkgetin/ginkgetin and
      quercetin treatments lowered cytotoxicity indices to 50.81, 67.81 and 62.19%,
      respectively, compared to 95.38% for the untreated control. The antioxidant
      potential of biflavones of Ginkgo biloba could be explained on the basis of
      structure-related activity; hydroxy- and methyl-substitutions on the basic
      structure of these flavonoids played a role, as other reports have suggested.

PMID- 11449671
TI  - A specific thrombin inhibitor, argatroban, alleviates herpes zoster-associated
      pain.
AB  - We report the result of a randomized, controlled, open trial of anti-thrombin
      therapy for herpes zoster-associated pain. Fifty-five herpes zoster patients
      within 8 days after the onset of skin lesion were enrolled in the trial. Patients
      were treated with an optimal dose of oral acyclovir (4000 mg/day for 7 days) with
      or without intravenous administration of a specific anti-thrombin agent,
      argatroban (10 mg/day, three times a week). Administration of argatroban reduced
      pain intensity at the 4th through 21st day after the initiation of treatment as
      determined by visual analogue scale (Mann-Whitney U test, p < 0.05). It also
      shortened the median time to cessation of analgesic use (14 days vs. 24 days, p =
      0.02, logrank test), although it did not significantly reduce the median time to
      cessation of pain (21 days vs. 43 days, p = 0.07, logrank test). None of the
      enrolled patients showed evidence of adverse effects including hemorrhagic
      diathesis. The results suggested that relatively low doses of argatroban are
      effective in reducing herpes zoster-associated pain. Up-regulation of prothrombin
      expression by the vascular endothelial and sweat gland epithelial cells in the
      active skin lesion and transient elevation of plasma thrombin-antithrombin III
      complex levels in a proportion of patients suggest a lesional generation of
      thrombin in herpes zoster. This may be relevant to the beneficial effects of the
      anti-thrombin treatment on the resolution of herpes zoster-associated pain.

PMID- 11449672
TI  - The effects of famciclovir and epidural block in the treatment of herpes zoster.
AB  - In our previous study, we concluded that an epidural blockade combined with
      intravenous acyclovir is very effective in treating the acute pain in herpes
      zoster and postherpetic neuralgia. We evaluated the efficacy of oral famciclovir
      and epidural blockade on the pain of herpes zoster, compared to acyclovir
      administered intravenously and epidural blockade. For this purpose, we examined a
      new group treated with famciclovir and epidural blockade to compare with the
      group treated with acyclovir and epidural blockade in our previously study. The
      changes in the intensity of pain, the number of days required for relief of pain,
      and the total duration of pain were checked. We compared the days required for
      relief of pain (DRP) and the total duration of pain (TDP) of this group with
      those of the previous studied group treated with acyclovir and epidural blockade.
      DRP was significantly less, but TDP was similar. DRP and TDP were significantly
      lower, if the patients were treated within 7 days of symptom onset. The patients
      had a shorter DRP regardless of pain type than the previously studied group
      treated with acycolvir and epidural blockade. For the severe and moderate pain
      grades, there was a shorter DRP from 100 to 10. TDP was not significantly
      different for the groups regardless of pain type or grade. We believe that
      famciclovir and epidural blockade are very effective in treating the pain of
      herpes zoster, with a view to shortening the period of acute pain, providing
      similar effects on the prevention of postherpetic neuralgia, and being convenient
      to administer, compared to intravenous acyclovir and epidural blockade in our
      previous study.

PMID- 11449673
TI  - Recessive epidermolysis bullosa dystrophicans (Hallopeau-Siemens)--improvement of
      wound healing by autologous epidermal grafts on an esterified hyaluronic acid
      membrane.
AB  - Epidermolysis bullosa dystropicans of the Hallopeau-Siemens type (HS-EBD) is an
      autosomal-recessive blistering disease. Skin fragility due to mutations in
      structural proteins is responsible for further development of chronic and painful
      wounds, skin infections and sepsis. There is no causative treatment available. We
      present a case report with HS-EBD and longstanding painful wounds treated with
      autologous keratinocytes on an esterified hyaluronic acid membrane. Two out of
      three wounds treated showed a complete take of the graft. They improved markedly
      with a stable result over 12 months until now. Even autologous keratinocyte
      grafting may have a beneficial effect on chronic wounds in HS-EBD despite the
      fact that the genetic defects are unchanged.

PMID- 11449674
TI  - Degenerated neurilemoma (ancient schwannoma).
AB  - We report a case of degenerated neurilemoma in a 65-year-old Japanese woman. A
      tumor in the right thigh histopathologically showed a mixture of Antoni type A
      and B patterns, and contained prominent blood vessels with hyalinized walls, but
      no calcification. The tumor cell nuclei of middle areas were large,
      hyperchromatic and often multilobed but lacked mitotic figures. The mucinous
      areas had few tumor cells. Antoni type A and B areas were S-100 protein positive,
      while mucinous areas and hyalinized vessels were negative.

PMID- 11449675
TI  - Plantar verrucous carcinoma: report of a case treated with Boyd amputation
      followed by reconstruction with a free forearm flap.
AB  - Verrucous carcinoma is a relatively rare, well-differentiated, squamous cell
      carcinoma. Although it is slow-growing and mimics benign skin lesions, it can
      cause extensive local destruction that necessitates amputation. It is often
      underdiagnosed as a benign tumor in its early course. We report a case of
      extensive verrucous carcinoma on a recalcitrant ulcer and a severe long-standing
      scar around it on the sole of the right forefoot, which had been treated as a
      benign tumor for more than two years. We treated it successfully with amputation
      of the foot and were able to spare the heel by using a free innervated forearm
      flap to cover the defect at the stump. The present case should remind clinicians
      that a verrucous lesion developing on a refractory ulcer may be a complex
      malignant neoplasm; an accurate diagnosis is difficult without a combination of
      clinical features and pathological findings from an adequately deep specimen.

PMID- 11449676
TI  - Hemilateral distribution of papular lesions on the buttock histologically
      resembling granuloma gluteale infantum.
AB  - Two Japanese girls had small grouped papules on the buttocks without diaper
      dermatitis or bacterial or fungal infection. These granulomas spontaneously
      regressed over two weeks, even though oral antibiotics were administered. We
      discuss this variant of granuloma gluteale infantum of Tappeiner et al.

PMID- 11449677
TI  - [Sugar metabolism by microorganisms in dental plaque].

PMID- 11449678
TI  - [Regulation of phospholipid synthesis in yeast].

PMID- 11449679
TI  - [Structure and function of human selenoprotein P].

PMID- 11449680
TI  - [Nano-structural biology of chromosomal DNA].

PMID- 11449681
TI  - [Stratum corneum ceramides: their function and origins].

PMID- 11449682
TI  - [Molecular mechanisms of pain].

PMID- 11449683
TI  - [Regulation of Cdk5 activity in post-mitotic neurons].

PMID- 11449684
TI  - [Situation of blindness in the world and prevention of blindness].

PMID- 11449685
TI  - [The present state of blindness in the world].
AB  - PURPOSE: To investigate the present state of blindness around the world. METHODS:
      The article reviews significant studies by WHO and literature on the topic.
      RESULTS: Current global estimates indicate that blindness affects close to 45
      million people, with nine out of ten blind people living in developing countries.
      Two-thirds or more of all blindness is avoidable, in that the causes are
      preventable or treatable. Cataract is the major cause of blindness in the world
      and the number of cases is increasing. The second cause is glaucoma, and the
      third is trachoma. The extent of disability of blindness itself is very high
      compared to that of other illnesses. Also, in terms of the burden of diseases in
      society, blindness is a relatively huge problem in the developing world.
      CONCLUSIONS: Intervention should be focused on the factors that have the higheat
      possibility of change. Manpower development is the most important countermeasure.
      The aid required to support developing countries is what can make them stand on
      their own in long term ophthalmic care.

PMID- 11449686
TI  - [Orbital development after enucleation without orbital implant in early
      childhood].
AB  - PURPOSE: To evaluate the development of orbital volume in five adults who
      underwent enucleation without orbital implant during early childhood, using
      reconstructed computed tomography(CT) images. MATERIALS AND METHODS: The orbital
      volume of 5 adults who underwent enucleation without orbital implants during
      early childhood was measured using CT images, and the results were compared
      between the anophthalmic orbit and the unaffected orbit in each case. The shape
      of maldevelopmental orbit and the relationship between orbital development and
      replacement of the prosthesis were also investigated. RESULTS: Orbital
      development in patients who underwent enucleation without orbital implant during
      early childhood was delayed in comparison with the unaffected orbit, and the
      delayed development was especially remarkable at the part of orbit corresponding
      to the equator of the eyeball. Maldevelopment of the orbit was severer in cases
      without replacement of the prosthesis than with it. CONCLUSION: For the
      development of orbital volume in anophthalmos after enucleation, orbital volume
      in place of the eyeball is required. Therefore, orbital implantation at the time
      of enucleation and replacement of the prosthesis with larger ones as the body
      grows are important.

PMID- 11449687
TI  - [Three ocular sarcoidosis patients examined by indocyanine green angiography].
AB  - PURPOSE: To assess the findings of indocyanine green angiography(IA) in patients
      with ocular sarcoidosis. SUBJECTS AND METHODS: Three active ocular sarcoidosis
      patients with various retinochoroidal findings diagnosed by biopsy or systemic
      examination. Two patients were diagnosed pathologically and one patient was
      diagnosed clinically. IA & fluorescein angiography(FA) were performed before and
      after treatment with systemic steroid administration. RESULTS: IA revealed
      hyperfluorescence surrounding the presumed granulomatous lesions. This
      hyperfluorescence disappeared immediately after the treatment. FA showed
      hyperfluorescence continuing even after therapy. CONCLUSIONS: It is purposed that
      the ring-form hyperfluorescence in IA is due to accelerated vascular permeability
      in the active sarcoid granuloma. IA, which vividly reflects activity of sarcoid
      lesions, is an important tool for clinical evaluation of ocular sarcoidosis.

PMID- 11449688
TI  - [Comparison between the anterior chamber configuration in the supine position and
      that in the prone position in patients with narrow angle].
AB  - PURPOSE: To determine whether the anterior chamber configuration of patients with
      narrow angle is changed in the prone position. PATIENTS AND METHODS: The study
      included 16 eyes of 16 patients whose anterior chamber angle was classified as
      Shaffer 2 or narrower. The prone position test(PPT) and ultrasound biomicroscopy
      (UBM) were performed on every subject. In the UBM examination, the following
      parameters were measured both in the supine position and in the prone position:
      the angle-opening distance at 250 microns from scleral spur(AOD 250), the angle
      opening distance at 500 microns from scleral spur(AOD 500), the trabecular-iris
      angle(TIA), and the anterior chamber depth at the center of the cornea(anterior
      chamber depth, ACD). RESULTS: While the intraocular pressure was higher after PPT
      than before the test, every subject was evaluated as negative for PPT. Mean value
      of every parameter examined was lower in the prone position than in the supine
      position(AOD 250: 114 microns, vs. 128 microns, AOD 500: 121 microns vs. 144
      microns, TIA: 12.1 degrees vs. 15.5 degrees, ACD: 1966 microns vs. 2002 microns),
      and the change in ACD was statistically significant (p = 0.013). CONCLUSIONS: The
      anterior chamber configuration of patients with narrow angle is changed in prone
      position. Such a change can occur in patients classified as negative for PPT.

PMID- 11449689
TI  - [The sub-classification and long-term prognosis of preproliferative diabetic
      retinopathy].
AB  - PURPOSE: We followed eyes with preproliferative diabetic retinopathy(PPDR) for 2
      or more years, and then evaluated the proportion of patients developing
      proliferative diabetic retinopathy(PDR) and the period from diagnosis of PPDR
      until development of PDR. SUBJECTS AND METHODS: We divided 95 eyes affected by
      PPDR into 75 eyes with mild type and 20 eyes with moderate type based on our
      previously proposed sub-classification, and evaluated the long-term prognosis of
      2 or more. RESULTS: The proportion developing PDR was 24% in mild type and 60% in
      moderate type. The average period from diagnosis of PPDR until development of PDR
      was 6 years and 5 months in the mild type and 2 years in the moderate type. The
      accumulative occurrence rates of PDR at two, 5, and 10 years were estimated to be
      0%, 14%, and 39% in the mild type and 35%, 58%, and 79% in the moderate type,
      respectively. The proportion developing PDR was significantly higher and the
      average period until PDR development significantly shorter in the moderate than
      in the mild type. In mild type eyes, the rate of progression to moderate type was
      56% and further progression from moderate type to PDR was noted in 43%.
      CONCLUSION: The above results again verify the usefulness of our sub
      classification, and also provide useful information about the long-term prognosis
      of PPDR.

PMID- 11449690
TI  - [Amiodarone-induced keratopathy].
AB  - BACKGROUND: We studied 17 patients who received oral administration of
      amiodarone. CASES: The patients were 13 males and 4 females with the mean age of
      65.7 years. The periods of follow-up observation ranged from 120 to 1,085 days.
      Keratopathy was found in 7 cases(41.2%), during the follow-up period. The grade
      of keratopathy showed no fixed tendency in age, total drug dose, or duration of
      administration, nor was there any correlation between the grade on the one hand
      and the period from inception of amiodarone administration to the development of
      keratopathy and total drug dose on the other. The effects of amiodarone on the
      cornea, conjunctival epithelium, anterior subcapsular lens, and tear fluid were
      studied histologically in 2 cases. Effects of amiodarone were found in the cornea
      and anterior subcapsular lens, but not in the conjunctival epithelium and tear
      fluid. CONCLUSION: It is possible that keratopathy may be an indicator for long
      term administration and for predicting the development of other complications of
      amiodarone.

PMID- 11449691
TI  - [Evaluation of the conjunctiva of leprosy patients using impression cytology].
AB  - OBJECTIVE: To evaluate ocular surface disorders (OSD) similar to cicatricial
      pemphigoid in leprosy patients. SUBJECT AND METHOD: Sixteen leprosy patients were
      examined. They were under treatment as inpatients at the Tama Zenshoen National
      Sanatorium, an institution for the treatment of leprosy. In addition to routine
      ophthalmological examinations, the patients conjunctival goblet cells were
      examined using impression cytology. OSD similar to ocular cicatricial pemphigoid
      were defined as the presence of at least two items of the following:
      symblepharon, cicatricial contraction of the conjunctival sac, corneal
      neovascularization, and palpebral entropion. RESULTS: OSD was present in 8 of the
      16 patients (50%). Goblet cells were either decreased in number or absent in 7
      cases(44%), and included 4 cases with OSD. Six of the 7 cases(86%) with reduced
      or absent goblet cells had been diagnosed as leprosy prior to 1944. CONCLUSION:
      Reduction or absence of goblet cells is a frequent feature in leprosy patients,
      particularly in longstanding ones of 56 years or more. Insufficient initial
      treatment appears to be a major cause of this finding.

PMID- 11449692
TI  - [Standard values of inter-inner canthal, inter-outer canthal, and inter-pupillary
      distances in normal Japanese infants and children].
AB  - PURPOSE AND MATERIALS: We studied inter-inner canthal distance(DIC), inter-outer
      canthal distance (DOC), and inter-pupillary distance (PD) in 1,006 normal
      Japanese infants and children to establish the normal ratio of DIC/PD and DOC/DIC
      for the diagnosis of congenital anomalies such as Waardenburg syndrome. RESULTS:
      DIC, DOC, and PD increased significantly from one month after birth to 12 years
      of age. DIC and DOC were stable but PD increased from 13 years of age to 15 years
      of age in junior high school. The DIC/PD and DOC/DIC averages were 0.61 and 2.73,
      respectively, one month after birth and 0.63 and 2.69 at three months after
      birth. On the other hand, DIC/PD and DOC/DIC were stable at 0.55-0.59 and 2.45
      from 8 to 15 years of age. CONCLUSION: Since there have been no reports on
      standard values of DIC, DOC and PD in infants, we established the standard values
      in this study. These values are expected to be very useful in the diagnosis of
      neural crest cell migration anomalies, such as Waardenburg syndrome.

PMID- 11449693
TI  - [A case of choroidal hemangioma with bullous exudative retinal detachment treated
      successfully by transpupillary thermotherapy].
AB  - BACKGROUND: Choroidal hemangioma associated with bullous retinal detachment may
      be difficult to treat, due to varying results with conventional laser
      photocoagulation, radiotherapy, or surgical drainage. Here we report on a case of
      extensive bullous retinal detachment secondary to circumscribed choroidal
      hemangioma that was resolved after combined treatment with vitrectomy, silicone
      oil tamponade, and transpupillary thermotherapy. CASE: A 29-year-old woman
      presented with a large choroidal hemangioma in her right eye associated with
      serous retinal detachment. The tumor measured 8 disc diameters in size and was
      located in the inferotemporal macula, abutting the fovea. RESULTS: Laser
      photocoagulation of the tumor was unsuccessful in inducing absorption of
      subretinal fluid. Because of progressive bullous retinal detachment, surgery was
      performed consisting of external drainage of subretinal fluid, vitrectomy,
      endolaser photocoagulation of the tumor, and silicone oil tamponade. The silicone
      oil was removed four weeks postoperatively at which time almost complete
      resolution of the retinal detachment was observed. However, retinal detachment
      recurred eight weeks later, and transpupillary thermotherapy was then applied to
      the tumor. By four weeks after transpupillary thermotherapy, total reabsorption
      of subretinal fluid, visual acuity improvement, and decreased height of the
      choroidal hemangioma were noted. CONCLUSION: Transpupillary thermotherapy is an
      effective treatment for serous retinal detachment associated with choroidal
      hemangioma.

PMID- 11449694
TI  - [Intracameral suturing technique using the Kawano cannula].
AB  - BACKGROUND: Intracameral suturing procedures are often so difficult that new
      techniques need to be devised. CASE: A case of photophobia caused by the
      pupillary distortion after anterior chamber lens implantation in cataract surgery
      with vitreous loss. METHODS AND RESULTS: In contrast to use of the healon
      cannula, pupilloplasty was more easily and safely performed using the Kawano
      irrigation cannula (M-91, Inami, Tokyo) by supporting and/or pressing the iris
      with the wide, flat distal end of the instrument, and also by inserting the
      needle end into the cannula through the large created port. CONCLUSION: The
      Kawano irrigation cannula is a safe and useful tool in intraocular suturing
      procedures.

PMID- 11449695
TI  - [Infants 12 month-old or less as a high risk group in tuberculosis--comparison of
      clinical data with those in children aged one to two years].
AB  - A number of tuberculosis (TB) infants 12 month-old or less is larger than the
      ones of any other age groups with childhood TB in our hospital. This study was
      undertaken to elucidate clinically why infants 12 month-old or less suffered from
      TB most among infants and early children. We studied tuberculin skin reaction,
      isolation frequency of Mycobacterium tuberculosis (MTB) in gastric aspirates, and
      frequency of systemic dissemination of TB among 45 TB infants 12 month-old or
      less, and compared the results with those of 31 control TB infants and children
      aged 13 to 35 month-old. The frequency distribution of tuberculin skin reaction
      size among the studied infants was significantly smaller than that among the
      controls (p < 0.05). MTB was positive among 33 out of the 45 studied infants
      (73%) while 12 out of the 31 controls (39%), and the difference was significant
      (p < 0.005). Miliary TB and/or TB meningitis were seen among 8 out of the 45
      studied infants (18%) while 1 out of the 31 controls (3%), and there was
      marginally significant difference between them (p = 0.054). These results suggest
      that delayed-type hypersensitivity and cell-mediated immunity to MTB among
      infants 12 month-old or less may be lower than those among infants and children
      aged 13 to 35 month-old, and the studied infants may be inferior in their
      capacity to kill mycobacteria and to encapsulate mycobacteria by granuloma
      formation.

PMID- 11449696
TI  - [Profiles of expression of the therapeutic efficacy of KRM-1648 in mice infected
      with Mycobacterium avium complex at different challenge doses].
AB  - Studied were made on the profiles of the therapeutic efficacy of KRM-1648 (KRM)
      against Mycobacterium avium complex (MAC) infection, which was induced in mice at
      different challenge doses, in reducing bacterial growth in the visceral organs
      and altering the profiles of cytokine mRNA expression at the sites of infection.
      First, bacterial growth in the lungs of mice infected with either high or low
      challenge doses of MAC, was reduced due to KRM treatment. This effect was noted
      even in the early phase of infection (week 4) in mice, that were given a high
      dose infection. Second, marked therapeutic efficacy of KRM was observed in mice,
      that were given low-dose MAC infection, in terms of the reduction in bacterial
      loads in the spleen. However, in mice given a high-dose bacterial challenge, KRM
      did not exhibit such an efficacy. Third, the expression of both proinflammatory
      cytokines (TNF-alpha, IFN-gamma) and anti-inflammatory cytokines (IL-10, TGF
      beta) in mRNA levels were increased at 4 weeks after infection. Notably, all of
      the cytokines tested for the mRNA expression levels were higher in mice given a
      low-dose MAC infection as compared to those in mice given a high-dose infection.
      KRM treatment increased the mRNA levels of these cytokines at week 4, while TGF
      beta mRNA expression at week 8 was conversely decreased by KRM treatment. These
      findings suggest that the profiles of the therapeutic efficacy of KRM vary in
      mice given low- or high-dose MAC infection.

PMID- 11449697
TI  - [Evaluation of rapidly growing Mycobacteria isolates in a general hospital:
      reports from the hospital microbiology laboratory].
AB  - Forty isolates of rapidly growing Mycobacteria, Mycobacterium fortuitum group
      including M. fortuitum and M. peregrinum and M. chelonae group including M.
      chelonae subsp. chelonae and M. chelonae subsp. abscessus at Showa University
      Fujigaoka Hospital collected between February 1981 and December 1997 were
      investigated in this study. These isolates were from the patients who were not
      infected with HIV. The average age of fourteen patients, from whom M. fortuitum
      group was isolated, was 58 years, ranging from 17 to 80 years old. One patient
      (71-year-old) with chronic myelogenous leukemia and another (64-year-old) with
      chronic diabetes mellitus were diagnosed with skin abscesses of M. fortuitum
      group, which were located on the right site of the neck and in the scar after
      injecting insulin (injection abscess), respectively. The average age of twenty
      six patients, from whom M. chelonae group was isolated, was 57 years, ranging
      from 32 to 84 years old. One patient (75-year-old) with articular rheumatism was
      diagnosed with a lung infection of mixed M. chelonae group and Pseudomonas
      aeruginosa, and another (74-year-old) with diabetes mellitus and kidney failure
      was strongly suspected of a lung infection. The isolates of the two mycobacteria
      from the remaining patients were due to colonization, while these patients had
      the following underlying diseases contributing to infections: pulmonary
      emphysema; diabetes mellitus; leukemia; collagen diseases; lung cancer; chronic
      kidney diseases; systemic lupus erythematosus; carcinomatous pleurisy;
      bronchiectasis; post-tuberculosis. Most isolates of the two mycobacteria were
      separated from the specimens of patients' respiratory tracts, but since M.
      chelonae group was a contaminant in the tap-water for diluting concentrated
      chlorhexidine, the organism happened to be isolated with the mucous membranes of
      the 6 patients' colons that were picked up while using the washed fiber-scope.
      These findings suggest that M. fortuitum and M. chelonae groups, in spite of the
      fact that they rarely cause infection, have a significant risk of infecting aged
      patients in general hospitals with various underlying diseases attributable to
      infections. As only a few colonies were isolated from patients' specimens in the
      majority of cases, it took time to carry out these clinical examinations, and to
      improve this "laboratory's delay", it is needed to make faster report to
      clinicians.

PMID- 11449698
TI  - [Clinical study on the cases in which INH or RFP was discontinued during
      treatment for pulmonary tuberculosis].
AB  - Short course regimens; 2HRZ (E)(S)/4HR (E), 6HRS (E)/3-6HR and 6-9HR have been
      accepted as a standard chemotherapy (SC) for initial treatment of pulmonary
      tuberculosis in Japan. We studied the frequency of the treatment completion, the
      causes of the treatment failure and the outcome of the patients in whom INH or
      RFP was discontinued within 6 months after starting SC. The subjects included 597
      newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16
      national hospital in 1996. Results were as follows. 1. In 47 (7.9%) of the 597
      patients, either INH (19; 3.2%) or RFP (33; 5.5%) was discontinued. These 47
      cases were defined as a SC incompleted group and the other 550 as a SC completed
      group. 2. The patients in the SC incompleted group were seen more frequently in
      the ages of 20s (11.9%), 50s (10.9%), 60s (11.7%) or 70s (11.4%). 21 (13.6%) of
      154 female patients and 26 (5.9%) of 443 male patients were in the SC incompleted
      group. 3. The causes of cessation of INH or RFP were drug side effects (33;
      5.5%), drug resistance (10; 1.7%) and complications or underlying diseases (8;
      1.3%). 4. Fever or eruption (19; 3.2%) and drug induced hepatitis (12; 2.0%) were
      frequently seen as drug related side effects causing the cessation of INH or RFP.
      5. The rate of culture negative conversion of TB bacilli at 6 months after the
      start of the treatment was 98.9% in the SC completed and 88.9% in the SC
      incompleted group respectively. In the SC incompleted group, there were three
      cases continuously positive and two other patients who relapsed and became
      culture positive again. In these five patients, INH or RFP was discontinued
      because of drug resistance.

PMID- 11449699
TI  - [Long-term outcome of monotherapy by Cohen ureterocystoneostomy for
      vesicoureteral reflux in spina bifida patients].
AB  - BACKGROUND: The conventional surgical treatment for vesioureteral reflux (VUR) is
      spina bifida patients is ureterocystoneostomy. Various newer therapies, including
      augmentation enterocystoplasty and minimally invasive subureteral collagen
      injection, have been introduced. However, all of these procedures have specific
      advantages and disadvantages, and no guidelines for deciding on the surgical
      treatment of VUR in spina bifida patients have yet been established. In this
      study, the long-term outcome of the Cohen procedure, a method of
      ureterocystoneostomy, was examined. PATIENTS AND METHODS: Among spina bifida
      patients in whom VUR was treated by the Cohen procedure alone from 1984 to 1989,
      27 patients who could be followed up for 5 years or longer were enrolled in the
      study (11 males and 16 females, with a mean age of 13.4 years at surgery). In
      principle, they were followed up using annual cystography, excretory urography,
      and blood and urine tests. At the final assessment, they were examined for the
      presence at VUR and for morphological abnormalities of the urinary tract. Their
      renal function was also assessed. They were followed for 6 to 13 years (mean: 8.9
      years), and the mean age at final assessment was 22.2 years. RESULTS: Among 42
      ureters in the 27 patients examined, 38 ureters (90.5%) in 22 patients (81.5%)
      did not have VUR postoperatively. Four ureters in 4 patients had the recurrence
      of VUR, and in another patient new occurrence was detected postoperatively.
      Augmentation ileocystoplasty was performed to treat the postoperative decrease of
      bladder compliance in 4 patients. Among 22 patients who had hydronephrosis
      preoperatively, 9 (40.9%) showed improvement and none suffered from aggravation
      of this condition. None of the patients showed a decline of renal function,
      except for 1 who had a serum creatinine of 2.5 mg/dl preoperatively and developed
      end-stage renal failure at 7 years postoperatively. CONCLUSIONS: The Cohen
      procedure has an excellent anti-reflux effect. It is one of the therapeutic
      options for VUR in patients with good bladder compliance.

PMID- 11449700
TI  - [Clinical outcome of potassium-titanyl-phosphate (KTP/532) laser vaporization
      prostatectomy for benign prostate hyperplasia].
AB  - OBJECTIVE: To study the feasibility of vaporization prostatectomy by potassium
      titanyl-phosphate (KTP/532) laser in men with bladder outlet obstruction due to
      benign prostatic hyperplasia (BPH) and to evaluate their clinical and voiding
      outcome 2 weeks and 6 months after operation. PATIENTS AND METHODS: Laser
      vaporization prostatectomy with the KTP/532 laser at 20 W was performed in 21 BPH
      patients varying from 56 to 75 years of age. All cases were performed under the
      spinal anesthesia. The laser was produced by MODEL SL20/50 and ADD/Stat side
      firing fibers were used. A urethral catheter was inserted post-operatively and
      was removed within 6 days after operation. The hemoglobin value was examined on
      the first day after operation and uroflowmetry was executed 2 weeks and 6 months
      after operation with the examination of the residual urine volume. IPSS and QOL
      score were recorded by patients 2 weeks and 6 months after operation. RESULTS:
      The prostate volumes ranged from 22 to 52 mL (mean 37.3 +/- 10.4). None of the 21
      patients had any significant blood loss or any fluid absorption. The voiding
      parameters improved: mean peak flow rate increased from 7.1 to 16.5 mL/s 2 weeks
      after operation and to 15.2 mL/s 6 months after operation and residual volume
      decreased from 172 to 45 mL 2 weeks after operation and to 43 mL 6 months after
      operation. IPSS and QOL score improved significantly in Wilcoxon signed-ranks
      test. The ratio of excellent and good in efficacy criteria of Kawabe group was
      71.4% 2 weeks after operation and that was 71.4% 6 months after operation. Mean
      catheterization term was 4.5 days. Only one patient showed transient urinary
      retention when the catheter was removed the third postoperative day. None had
      incontinence postoperatively. No other significant complications were recognized.
      The prostate volume was more than 50 mL in 3 cases and the postoperative 6 months
      outcomes of the 3 cases were all poor in their symptoms in the efficacy criteria
      of Kawabe group. CONCLUSIONS: KTP laser vaporization prostatectomy is safe and
      effective for obstructive prostates up to 50 mL in volume and produces good
      results 2 weeks post operatively that are sustained for 6 months after operation.

PMID- 11449701
TI  - [Transperitoneal laparoscopic radical prostatectomy with the Montsouris
      technique: experience in initial 5 cases].
AB  - PURPOSE: In 1998 Guillonneau et al reported feasible and safe technique for
      laparoscopic radical prostatectomy. Herein we review initial 5 cases with using
      the Montsouris technique. MATERIALS AND METHODS: Between January and April 2000,
      5 patients underwent transperitoneal laparoscopic radical prostatectomy. Clinical
      stages were T1c in 2, T2a in 1 and T2b in 2 patients. Preoperative PSA levels and
      Gleason grades in needle biopsies ranged from 7.9 to 39 ng/ml and from 2 to 6,
      respectively. Under general anesthesia 5 to 6 trocars were introduced and the
      patient was placed in the exaggerated Trendelenburg position. In 2 patients
      bilateral obturator lymph nodes were dissected for frozen pathological
      examination. Antegrade prostatectomy was performed initiating with the
      transperitoneal dissection of seminal vesicles. A watertight vesicourethral
      anastomosis was made with 8 to 10 interrupted sutures. RESULTS: Operating time
      and blood loss ranged from 505 to 925 minutes and from 100 to 700 gm,
      respectively. There were no intraoperative complications and one postoperative
      complication of prolonged urinary leakage, which was spontaneously closed. In
      other 4 patients Foley catheters were removed on postoperative day 6 to 10.
      CONCLUSIONS: Laparoscopic radical prostatectomy provides better visualization,
      inducing meticulous surgical procedures and less blood loss. More sophisticated
      maneuver would be required in dissection between the prostate and the bladder
      neck.

PMID- 11449702
TI  - [Age-related changes in lower urinary tract symptoms and urodynamic parameters in
      patients with benign prostatic hyperplasia treated by transurethral resection of
      the prostate].
AB  - PURPOSE: To characterize age-related clinical and urodynamic features of patients
      with benign prostatic hyperplasia (BPH) treated by transurethral resection of the
      prostate (TUR-P). MATERIALS AND METHODS: Between July 1994 and March 2000, a
      total number of 451 patients underwent TUR-P in Nagoya Urology Hospital. Out of
      these 451 patients, 15 (3.3%) were diagnosed as having an incidental prostate
      cancer on pathological examination of resected prostate tissue. The remaining 436
      patients (48-92 years, 69.8 +/- 7.4 years), in whom 196 (45.0%), 208 (47.7%) and
      32 (7.3%) were < or = 69, 70-79 and > or = 80 years, respectively, were subjects
      for the present study. Their clinical features before and after TUR-P and the
      therapeutic effects of the treatment were evaluated in terms of aging. RESULTS:
      Among preoperative variables evaluated, IPSS in patients aged < or = 69 years was
      significantly higher than in those aged 70-79 years (p < 0.05). The QOL index was
      significantly higher in patients aged > or = 80 years than in those aged 70-79
      years (p < 0.05). The maximum bladder capacity decreased with age from 276 ml in
      patients aged < or = 69 years to 211 ml in those aged > or = 80 years.
      Postoperatively, both maximum and mean flow rates were significantly lower in
      patients aged 70-79 and > or = 80 years compared to those aged < or = 69 years.
      There was, however, no significant age-related difference in IPSS and QOL index.
      The assessment of treatment effects at 3 months following TUR-P revealed that the
      outcomes in function as evaluated by uroflowmetry, anatomy and ultrasonic
      measurement of prostate volume were significantly worse in patients aged > or =
      80 years compared to those in younger patients. However, there was no significant
      age-related difference in outcomes in subjective symptoms and QOL. CONCLUSIONS:
      TUR-P could be performed safely even in patients aged > or = 80 years. It is
      concluded that although postoperative urinary condition might be worse in older
      patients, they would nevertheless be satisfied with the results of TUR-P in the
      same way as less aged patients. As long as subjects are selected properly based
      on the correct diagnosis of BPH and a sufficient evaluation of operation risks,
      TUR-P can be expected to be performed safely and be followed by satisfaction with
      the treatment effects.

PMID- 11449703
TI  - [Le Duc-Camey procedure as a method of ureteroileal implantation on augmentation
      cystoplasty in patients with myelodysplasia].
AB  - PURPOSE: We investigated the results of Le Duc-Camey procedure as a method of
      ureteroileal implantation on augmentation cystoplasty in patients with
      myelodysplasia. MATERIALS AND METHODS: A total of 14 patients (25 renal units)
      underwent ureteroileal implantation with Le Duc-Camey procedure on augmentation
      cystoplasty. The possible causes of complications concerning ureteroileal
      implantation that developed during the postoperative observation were classified
      as preoperative factors and postoperative factors.: The preoperative factors were
      the causative disease required ureteroneostomy, the grade of preoperative VUR,
      and the ureteral diameter at the anastomosis with the ileum.: The postoperative
      factors were the volume, and the compliance of the urinary bladder, and the
      maximum intravesical pressureled by the peristalsis of the utilized intestine.
      RESULTS: With the mean observation period of 31.6 months, no complications
      developed but VUR observed in 4 renal units of 4 patients. The patients with VUR
      had a larger ureteral diameter at the anastomosis site to the ileum among the
      preoperative factors and a significantly larger maximum intravesical pressure led
      by the intestinal peristalsis among the postoperative factors when compared with
      the patients without VUR. CONCLUSION: Regarding ureteroileal implantation with Le
      Duc-Camey procedure on augmentation cystoplasty in patients with myelodysplasia.
      It seems necessary to consider some countermeasures for the dilated ureters and
      for the unexpected 2 elevation of intravesical pressure due to the peristalsis of
      the utilized intestine.

PMID- 11449704
TI  - [A case of tuberculosis of the prostate presenting as endoscopically cavitary
      change].
AB  - A 62-year-old man was admitted to our hospital with the chief complaint of
      terminal macroscopic hematuria. He had a history of left tuberculous epididymitis
      in 1994. On digital rectal examination, the prostate was found to be a normal
      size and slightly hard with no elasticity. Transcrectal ultrasound showed
      hypoechoic lesions in the peripheral zone. T1-weighted MRI demonstrated cavitary
      lesions and T2-weighted MRI demonstrated relatively low signal intensity in the
      same zone. Urethrography revealed various cystlike lesions in the prostatic
      urethra. Cystourethroscopy revealed cavitary change with many septa in the left
      lobe of the prostate. TUR-P was performed and histological findings of the
      specimen revealed tuberculosis of the prostate. The patient was treated with an
      antituberculous regimen of INH, RFP and EB.

PMID- 11449705
TI  - [Septic shock due to pyonephrosis-calculosa: a case report].
AB  - A 69-year-old female was admitted to hospital with the complaint of high-grade
      fever and clouding of consciousness. Physical examination and laboratory data
      revealed septic shock, disseminated intravascular coagulation and multiple organ
      failure. Ultrasonography demonstrated left hydronephrosis and a cystic mass in
      peri-renal fatty tissue. KUB showed a left ureteral stone. A diagnosis of septic
      shock due to pyonephrosis-calculosa and peri-renal abscess was considered. A left
      nephrectomy, endotoxin removal therapy and continuous hemodiafiltration was
      performed. Thereafter all morbidities improved. A nephrectomy and intensive
      treatment are the good alternative method for such a case.

PMID- 11449706
TI  - [A case of very rare tuberculosis of the testis].
AB  - A 61-year old man visited our hospital with a painless swelling of right scrotal
      contents as the chief complaint. Transillumination test of the right scrotal
      contents was negative, and a quail's egg sized, elastic hard and smooth
      induration in the right testis was palpable. The laboratory data were normal
      except for slightly elevated E.S.R and CRP. Urine examination was normal.
      Although not only tumor marker, beta-hCG, AFP and LDH but also Plain lung X-ray,
      DIP and CT were normal, ultrasonography and MRI revealed a well-defined nodule in
      the right testis. Under the diagnosis of right testicular tumor, right high
      orchiectomy was performed. A yellowish white nodule of 2.5 cm in diameter was
      found in the slightly enlarged right testis. Pathologically, the patient was
      diagnosed as having tuberculotic granuloma with necrotic caseation. However, the
      epididymis was histologically normal. After operation, an antitubercular
      medication was started. Subsequently, E.S.R and CRP became normalized. At
      present, 12 months after surgery, the recurrence is not found. Tuberculosis of
      testis which shows no lesion in the epididymis is very rare, and ours is the
      first reported case in the Japanese literature. The importance of tuberculosis as
      a revival infection should be recognized in social circumstance in which
      tuberculosis is beginning to spread again.

PMID- 11449707
TI  - [A case of vaginal implantation of transitional cell carcinoma of the bladder].
AB  - An 82-year-old female presented with asymptomatic gross hematuria in June 1997.
      Urethrocystoscopy revealed a multiple papillary tumor of the bladder and
      posterior urethra. Histology of the punch biopsy specimens of the tumor revealed
      transitional cell carcinoma (TCC), grade 2 (G2). CT scan showed no distant
      metastasis and extravesical invasion. The patient was treated by intravesical
      instillation of adriamycin (ADM), drip infusion of low dose cisplatin (CDDP) and
      irradiation of the bladder. As the treatment caused a significant tumor
      shrinkage, transurethral resection of the tumor was performed. Histologically,
      the tumor revealed no invasion to the muscular layer of the bladder. In April
      1998 she noticed genital bleeding, and a multiple papillary tumor was found on
      the vaginal wall. Histology of punch biopsy specimens of the vaginal tumor showed
      non-invasive TCC, G2. MRI and specimens of all layer needle biopsy showed no
      infiltration outside the bladder wall and the vaginal wall. Irradiation of the
      cavity of the vagina and uterus was made under the diagnosis of superficial
      vaginal TCC. We assume that vaginal implantation via irrigating fluid or urine
      has occurred.

PMID- 11449708
TI  - [Molecular biology of cerebral ischemia].

PMID- 11449709
TI  - [Diagnosis of cerebral aneurysm using 3-dimensional digital subtraction
      angiography].
AB  - Recent rapid advancement in the technology of magnetic resonance angiography and
      3-dimensional computed tomography angiography has opened the door to a less
      invasive diagnostic routine for the treatment of cerebral aneurysms. However,
      from the viewpoint of decision making concerning which treatment to use;
      conservative therapy; surgical intervention; or endovascular treatment, much more
      precise information is necessary. Recent progress of rotation digital subtraction
      angiography has introduced 3-dimensional digital subtraction angiography. In the
      past year, 28 cases involving 39 aneurysms have been studied using 3-dimensional
      angiography. This study was carried out, using a rotating C-arm, which rotates
      220 degrees in 5.8 seconds. All raw data gathered was transferred to the
      workstation for image reconstruction. The purpose of this study was to evaluate
      the clinical potential of 3-dimensional digital subtraction angiography for the
      diagnosis of the cerebral aneurysms.

PMID- 11449710
TI  - [Usefulness of three-dimensional CT angiography (3D-CTA) with a single bolus
      injection of contrast material for the examination of intracranial and cervical
      arteries in cerebrovascular disease screening].
AB  - Three-dimensional CT angiography (3D-CTA) has been gaining wide acceptance as a
      clinically useful tool in the field of neurosurgery. The great diagnostic value
      of 3D-CTA for cerebral aneurysm or other cerebrovascular diseases has been well
      established. However, images of the intracranial and cervical arteries have not
      been obtained simultaneously because of the limitation of the scanning area and
      the need for contrast material. In order to use 3D-CTA to screen for
      cerebrovascular disease, we used a helical CT scan with an intravenous single
      bolus injection of contrast material to perform 3D-CTA of the intracranial and
      cervical arteries simultaneously. A spiral computed tomographic scan was
      performed with a Hispeed Advantage RP (General Electric). After injection of 150
      ml of nonionized contrast material at a rate of 3 mm/sec in an antecubital vein,
      an axial computed tomographic scan (120 kV, 200 mA) of the cranial region was
      performed with a delay of 20-25 seconds after starting the injection. Section
      thickness was 1 mm with table increments of 1 mm per rotation. The scan volume
      included 20-30 mm above and below the sella turcica. An axial computed
      tomographic scan (120 kV, 190 mA) of the cervical region was performed with a
      delay of 30 seconds after completion of cranial CTA. Section thickness was 3 mm
      with table increments of 3 mm per rotation. Image reconstruction was carried out
      through surface rendering and maximum intensity projection processing. From
      November 1995 to August 1998, we used this technique to screen 218 consecutive
      outpatients for cerebrovascular disease. Unruptured cerebral aneurysms were found
      in 20 cases (9.2%). Atherosclerotic diseases of the cervical carotid artery were
      found in 58 cases (26.6%), as follows: carotid artery occlusion in 2 cases,
      carotid bifurcation stenosis in 22 cases, and intramural calcification of the
      internal carotid artery in 50 cases. Atherosclerotic diseases of the intracranial
      artery were found in 99 cases (45.4%), as follows: middle cerebral artery
      occlusion in 2 cases, middle cerebral artery stenosis in 21 cases, internal
      carotid artery stenosis in 2 cases, and calcification of the carotid siphon in 78
      cases. Although our method has various technical problems that require further
      improvement, we conclude that it is a useful and noninvasive diagnostic modality
      for screening patients for cerebral aneurysms and other cerebrovascular diseases.

PMID- 11449711
TI  - [A case of gliomatosis cerebri: remarkable improvement after radiation therapy].
AB  - A 30-year-old female case of gliomatosis cerebri, which showed remarkable
      improvement after radiation therapy is reported. The lesion had spread widely in
      the frontal and parietal lobes of both sides, causing diffuse swelling of the
      cerebral hemispheres. A specimen obtained by open biopsy revealed diffuse
      proliferation of astrocytic (GFAP positive) tumor cells, associated with little
      tissue destruction. After whole-brain radiation of 60 Gy, the lesion shrunk
      gradually but markedly. Hemiparesis and mild dementia, which the patient had
      experienced before treatment, subsided completely within 6 months, until she was
      able to restart her job as a dentist. Although gliomatosis cerebri is thought to
      have a poor prognosis, this case demonstrates the potential of radiotherapy for
      this disease. Factors which may lead to a better outcome are discussed.

PMID- 11449712
TI  - [The early hemorrhage and development of a bacterial aneurysm after a cerebral
      ischemic attack caused by a septic embolism--a case report].
AB  - A 71-year-old female was admitted with the complaints of dysarthria and right
      hemiparesis. CT scan revealed subarachnoid hemorrhage in the left cerebral
      sulcus. The first angiography was performed 3 days after the onset and left
      carotid angiography revealed a small aneurysm arising from the left middle
      cerebral artery. After 3 weeks of antibiotic therapy, the second angiography
      showed the aneurysm to be clearly enlarged, so it was resected. The patient
      complained of marked dysarthria a day after the operation and CT scan revealed a
      new infarction in the right frontal lobe. The third angiography showed an
      aneurysm arising from the right middle cerebral artery and the fact that two
      peripheral arteries of the aneurysm had disappeared 3 weeks after the first
      operation. The second operation was performed and a bacterial aneurysm was
      resected. The patient left the hospital without any neurological deficits. Septic
      embolism is the most important complication of infective endocarditis and it is
      usually presented with subarachnoid hemorrhage and intracerebral hemorrhage
      caused by ruptured bacterial aneurysms. In this case the septic embolism occurred
      two times. At each time cerebral ischemic attacks were presented. The reason why
      this case presented with ischemic symptoms was suspected to be that embolisms
      occurred at the trifurcation of the distal middle cerebral arteries. We were able
      to detect a bacterial aneurysm angiographically 3 days after the ischemic attack
      and we suspected that a bacterial aneurysm had been able to develop within 3 days
      after the septic embolism.

PMID- 11449713
TI  - [Dural arteriovenous fistula of the anterior cranial fossa associated with
      occlusion of the internal carotid artery: a case report].
AB  - We reported a case with dural arteriovenous fistula (dAVF) of the anterior
      cranial fossa associated with occlusion of the left cervical internal carotid
      artery. A 73-year-old man was admitted with total aphasia and right hemiparesis.
      Computed tomography showed an ischemic lesion of the left cerebral hemisphere and
      old infarction of the left occipital lobe. Angiography revealed occlusion of the
      left cervical internal carotid artery and dAVF of the anterior cranial fossa, fed
      by the left middle meningeal and the right anterior ethmoidal artery. Follow-up
      angiography revealed spontaneous recanalization and severe arteriosclerosis of
      the left internal carotid artery. After marked improvement of neurological
      deficits, the patient underwent surgical clipping of the draining veins to
      occlude the dAVF of the anterior cranial fossa. We speculated that marked
      development of the collateral circulation from the external carotid system might
      result in the occurrence of dAVF of the anterior cranial fossa.

PMID- 11449714
TI  - [A giant thrombosed aneurysm of the anterior communicating artery which developed
      18 years after clipping: a case report].
AB  - A 64-year-old man, who had undergone clipping surgery 18 years before for a
      ruptured anterior communicating artery (ACoA) aneurysm, presented with mild
      aphasia. A computerized tomography (CT) scan showed a subcortical hemorrhage in
      the left temporal lobe, and a high density large mass at the ACoA. Neuro-imaging
      study revealed a giant thrombosed ACoA aneurysm. Thrombectomy and neck clipping
      were successfully performed, using the interhemispheric approach. The patient was
      discharged without additional neurological deficits. A long-term follow-up study
      is thus considered necessary after neck clipping of a ruptured aneurysm.

PMID- 11449715
TI  - [Extracranial metastasis of glioblastoma to the lung and heart with a
      histological resemblance to small cell carcinoma of the lung: an autopsy case].
AB  - An autopsy case of small cell glioblastoma, showing multiple extracranial
      metastases, is reported with special reference to histopathological
      differentiation from metastatic small cell carcinoma. Widely spread lesions in
      the bilateral lungs were developed after an operation and chemo-radiotherapy for
      glioblastoma, and the lung lesions led to fatal respiratory failure. Postmortem
      examination revealed multiple tumors in the lung, lymph nodes, and the heart, as
      well as local invasion of the primary tumor to the dura, skull, and the scalp.
      The mechanism of extracranial metastasis of brain tumor is discussed.

PMID- 11449716
TI  - [A case of a multiple sclerosis with severe perifocal edema].
AB  - We present a case of tumoral multiple sclerosis in a 66-year-old male and
      emphasize two clinical features: (1) Multiple well-demarcated massive enhanced
      lesions except for the central area, which was accompanied with severe perifocal
      edema, occurred within the cerebral hemispheres and should be strongly considered
      in the diagnosis of mass lesions. The patient underwent partial removal of the
      mass lesion. The initial histopathological diagnosis of the surgical specimen was
      astrocytoma grade II. (2) Multiple lesions disappeared completely for one and
      half months after starting medication using steroid. The reexamination of the
      surgical specimen was compatible with that of multiple sclerosis. Again, half a
      month after remission, multiple enhanced lesions without perifocal edema
      developed in the cerebral and cerebellar hemisphere. The difficulty of the
      initial diagnosis of multiple sclerosis with severe perifocal edema was
      discussed, based on our experience.

PMID- 11449717
TI  - [Aspiration and drainage for a gas-producing brain abscess causing delayed
      bleeding from the abscess capsule--a case report].
AB  - A 65-year-old man was admitted with the complaint of gait disturbance. CT scan
      revealed a low density lesion in the right parietal lobe. MRI was carried out 3
      days after admission, the lesion showing low intensity on T1 WI and T2 WI. Gd
      DTPA enhanced T1 WI showing abnormal enhancement surround it. CT scan then
      revealed a gas bubble in the lesion 12 days after admission, so we diagnosed it
      as gas-producing brain abscess and aspiration, drainage and irrigation with
      antibiotics were performed. Although, the brain abscess was reduced in size after
      the operation, the lesion expanded again 2 weeks after the operation. MRI was
      performed and the lesion showed iso-intensity on T1 WI and high intensity on T2
      WI. Emergent aspiration and drainage were performed and uncoagulated old-hematoma
      like matter such as chronic subdural hematoma was removed. As significant
      neovascularization with inflammatory cells had been detected in the capsule of
      the brain abscess, we suspected that aspiration and drainage surgery for brain
      abscess may cause delayed bleeding from the capsule of the abscess. We conclude
      that attention should be drawn to such a complication.

PMID- 11449718
TI  - [Anterior cerebral artery dissecting aneurysm associated with fibromuscular
      dysplasia (FMD): a case report].
AB  - We have recently encountered a rare case of anterior cerebral artery dissecting
      aneurysm, presenting cerebral infarction and subarachnoid hemorrhage, associated
      with fibromuscular dysplasia (FMD). A 50-year-old woman was admitted to our
      hospital with complaints of headache and hemiparesis. A right carotid angiogram
      obtained 9 hours after the onset revealed stenosis and slight dilatation in the
      A1 portion of the anterior cerebral artery. At 12 hours after the onset, the
      patient fell into a coma. CT scan showed diffuse subarachnoid hemorrhage. An
      angiogram had revealed aneurysmal dilatation and double lumen in the A1 portion,
      but, 34 days after the onset, angiogram showed growth of the aneurysm in the A1
      portion and stenosis in the A2 and A3 portions. At 38 days after the onset, the
      trapping of the dilated aneurysm to prevent rerupture was performed. Pathological
      diagnosis was concluded to be FMD. We concluded that FMD caused stenosis as well
      as the formation and rupture of the dissecting aneurysm in the anterior cerebral
      artery.

PMID- 11449719
TI  - [Cavernous sinus dural arteriovenous shunt presenting with subarachnoid
      hemorrhage and acute subdural hematoma: a case report].
AB  - Cavernous sinus dural arteriovenous shunt (CdAVS) usually presents with
      exophthalmos, conjunctival chemosis, ophthalmoplegia, headache, bruit, or
      pulsatile tinnitus. Intracranial hemorrhage associated with CdAVS is rare. We
      describe a patient with CdAVS presenting with subarachnoid hemorrhage and acute
      subdural hematoma. A 65-year-old woman presented headache and temporary loss of
      consciousness and was transferred to our hospital. On admission, the patient was
      alert and complained of a left-sided temporal headache. There were no ocular
      symptoms. A CT scan revealed subarachnoid hemorrhage and left acute subdural
      hematoma. When we prepared for cerebral angiography, the patient presented loss
      of consciousness following sudden onset of severe headache. Urgent angiography
      revealed left CdAVS, which was fed by both the internal carotid artery and the
      external carotid artery and drained only into ipsilateral (left) vein of the
      sylvian fissure. Aneurysmal dilatation of the draining veins and leptomeningeal
      drainage were present. No cerebral aneurysms were detected. After the
      angiography, a CT scan showed enlarged subdural hematoma, so left fronto-temporo
      parietal craniotomy was immediately performed. On opening the dura mater,
      arterial bleeding from Sylvian fissure appeared and was uncontrollable.
      Unfortunately, the patient died 3 days after the operation. We concluded that
      subarachnoid hemorrhage and subdural hematoma were due to the rupture of engorged
      cortical veins. Our case report suggests that CdAVS with angiographic findings
      such as aneurysmal dilatation of the draining veins and leptomeningeal drainage
      should be treated urgently because of the high risk of the life-threatening
      complications resulting from a surgically uncontrollable hemorrhage.

PMID- 11449720
TI  - [Acute hepatitis B virus after chemotherapy for a case with germinoma].
AB  - A 28-year old man with HCG-producing germinoma had undergone chemotherapy and
      radiotherapy. On admission for the fifth session of maintenance chemotherapy, he
      was found to be positive for hepatitis B (HB)s antigen, but negative for HBs
      antibody. HBs antigen had been negative during previous admissions. Since liver
      function was normal, the patient underwent chemotherapy. During myelosuppression
      after chemotherapy, liver dysfunction developed and acute HB was diagnosed. He
      fortunately showed seroconversion 2 months after onset. Serum immunological
      examinations are required for patients receiving chemotherapy.

PMID- 11449721
TI  - Bioinformatics and the Internet.

PMID- 11449722
TI  - Genomic mapping and mapping databases.

PMID- 11449723
TI  - Information retrieval from biological databases.

PMID- 11449724
TI  - Sequence alignment and database searching.

PMID- 11449725
TI  - The NCBI data model.

PMID- 11449726
TI  - Creation and analysis of protein multiple sequence alignments.

PMID- 11449727
TI  - Predictive methods using DNA sequences.

PMID- 11449728
TI  - Predictive methods using protein sequences.

PMID- 11449729
TI  - Expressed sequence tags (ESTs).

PMID- 11449730
TI  - Sequence assembly and finishing methods.

PMID- 11449731
TI  - Phylogenetic analysis.

PMID- 11449732
TI  - Comparative genome analysis.

PMID- 11449733
TI  - Large-scale genome analysis.

PMID- 11449734
TI  - Using Perl to facilitate biological analysis.

PMID- 11449735
TI  - The GenBank sequence database.

PMID- 11449736
TI  - Submitting DNA sequences to the databases.

PMID- 11449737
TI  - Structure databases.

PMID- 11449738
TI  - Rethinking access to alcohol treatment.

PMID- 11449739
TI  - Access to services in the substance abuse treatment system. Variations by
      facility characteristics.
AB  - In view of the importance of type and intensity of services during substance
      abuse treatment, this chapter looks at treatment and support services that
      substance abuse clients have access to during treatment. Trends in services over
      recent years are described. Services available to clients in the current
      treatment system are reviewed. Several facility characteristics affecting access
      to services are examined. Different ways of defining access to services are
      discussed. Findings from the Alcohol and Drug Services Study are used to
      illustrate service patterns in the national substance abuse treatment system.
      Variations in service patterns by facility characteristics such as type of care,
      treatment setting, ownership, percent of facility dependence on public revenue,
      and level of affiliation are analyzed. The implication is that clients who enter
      into treatment at different types of facilities are likely to have access to
      certain types of services.

PMID- 11449740
TI  - Patient placement criteria and their relation to access to appropriate level of
      care and engagement in alcoholism treatment.
AB  - Patient placement criteria (PPC) facilitate treatment matching through detailed,
      standardized assessment of patients' needs. This process affords the alcoholism
      treatment field an opportunity to address issues that influence access to
      appropriate level of care by highlighting these issues during the assessment. The
      American Society of Addiction Medicine Patient Placement Criteria can integrate
      assessment of social and environmental, institutional and patient issues that
      affect access to appropriate care and treatment engagement. They can ultimately
      improve access through an iterative approach: developing a broad consensus on
      guidelines based on research evidence and expert clinical opinion, making
      criteria clear and easy to use both for assessment and for teaching purposes,
      addressing the needs of special populations, and testing and improving the
      validity of decision rules to achieve optimal access and treatment engagement.
      Early evidence suggests that PPC are promising but there is much about them that
      remains to be tested and improved.

PMID- 11449741
TI  - Access to substance abuse services in rural areas.

PMID- 11449742
TI  - The role of health economics in substance abuse research. Recent advances and
      future opportunities. Overview.

PMID- 11449743
TI  - Economic evaluation of alcohol treatment services.
AB  - The objective of this paper is to summarize and critically review the most recent
      literature on economic evaluation of alcohol treatment services, identify
      information gaps, and suggest a research agenda for the future. The focus of the
      review is research published after 1995, although some of the earlier economic
      studies are also included. Research findings in the literature provide evidence
      for the following. First, for many alcoholics, day hospital treatment or even
      less intensive outpatient services are cost-effective alternatives to inpatient
      treatment. Second, alcoholism treatment often results in declining health care
      costs for alcoholics who are covered by private health insurance. Third, though
      the use of alcoholics anonymous (AA) as an alternative to more structured alcohol
      treatment services may be cost-effective, substance abuse outcomes from AA are
      sometimes less favorable and the risk of relapse is higher. Fourth, methods have
      recently been developed to estimate the dollar value of alcohol treatment
      outcomes such as avoided absenteeism, increased productivity, improved health,
      and avoided crime. Based on these findings and developments, new treatment
      approaches and changes in service delivery systems require a fresh perspective on
      the costs and benefits of alternative treatment services. The findings from
      economic evaluation studies must be reported in clear and nontechnical terms to
      an audience of clinicians and politicians so that they can be used in the process
      of decision making.

PMID- 11449744
TI  - Financing of substance abuse treatment services.
AB  - The financing of treatment for substance abuse problems has differed from the
      rest of financing of health care in part because of the dominant role of the
      public sector as the payer of services. Nonetheless, the rise of managed care has
      affected substance abuse treatment services as well as the rest of the health
      care system. Alternative payment mechanisms are one important component of some
      managed care approaches. Behavioral health carve-outs are another managed care
      development that has affected substance abuse services. In this chapter, salient
      features of financing for substance abuse treatment are reviewed within the
      conceptual framework of payers (purchasers and intermediaries), providers, and
      consumers. Existing literature on substance abuse treatment financing is
      summarized, while recognizing that much remains to be researched.

PMID- 11449745
TI  - Using cost and financing instruments for economic evaluation of substance abuse
      treatment services.
AB  - Standardized economic evaluation instruments are an important tool in the
      analysis of change and performance of addiction treatment. Nevertheless, compared
      to other health care sectors, economic evaluation of addiction treatment is still
      rare. The present paper proposes two comprehensive economic evaluation
      instruments that are methodologically sound and that meet the objectives of
      comprehensiveness, standardization, and comparability. The Drug Abuse Treatment
      Cost Analysis Program (DATCAP) can be used to estimate the economic cost of
      treatment services; the Drug Abuse Treatment Financing Analysis Program (DATFin)
      is a companion instrument and analyzes the complexity and change of treatment
      financing. This paper outlines the contents of each instrument and, for
      illustrative purposes, presents results from several case studies. Suggestions
      for updates and enhancements for each instrument are also discussed.

PMID- 11449746
TI  - The organization of substance abuse managed care.
AB  - Managed care came to dominate the delivery of substance abuse services during the
      1990s. This paper uses literature and new data to describe and analyze the set of
      arrangements it implies. The description suggests that substance abuse managed
      care typically is "carved out" of the general health care plan and treatment is
      coordinated by a behavioral health managed care company that manages treatment
      access, length, type, and intensity. This administrative agent is provided
      financial incentives to keep costs low and otherwise faces such mandates as to
      ensure timely access to treatment and to deliver reports. A typical agent has
      some interest in improving the quality of decision-making, but has few incentives
      for controlling the treatment technology. In contrast, agents tend to control
      treatment providers through relatively rigid rules that substitute outpatient for
      inpatient care, regulate the length and intensity of services, provide limited
      social services, mandate accreditation, allow limited clinician discretion,
      administer an entire "network" of providers as an only slightly differentiated
      mass, and rarely shape the details of the treatment process. These patterns are
      analyzed in terms of transaction cost economics and institutional and resource
      dependency theories. In general, it is argued that managed care reflects an
      interest in controlling costs but also in ensuring access within an environment
      where there is uncertainty accompanying competing demands, varying conceptions of
      the client, and controversies over the efficacy of specific treatment
      technologies.

PMID- 11449747
TI  - Alcoholism treatment in managed private sector plans. How are carve-out
      arrangements affecting costs and utilization?

PMID- 11449748
TI  - Problem drinking, health services utilization, and the cost of medical care.
AB  - The purpose of this study was to examine the relationships between problem
      drinking, health services utilization, and the cost of medical care in a
      community-based setting. In addition to descriptive analyses, these relationships
      were estimated with multivariate regression models. Data were collected in 1996
      and 1997 through a standardized self-administered questionnaire designed to
      obtain important information on demographics, health status, morbidity, health
      care utilization, drug and alcohol use, and related lifestyle behaviors. The
      survey instrument also included the 10-item Michigan Alcoholism Screening Test
      (MAST-10), which was used to identify problematic alcohol users (PAUs). The
      empirical findings indicated that PAUs had a significantly higher number of
      outpatient visits, more emergency room episodes, and more admissions to a
      hospital than a combined group of nondrinkers and nonproblematic alcohol users
      (NPAUs). Analyses of total health care cost showed that the estimated
      differential in total cost for PAUs during the past year, including the
      interaction effect with problematic drug use, was $367. The total cost (full
      effect) for PAUs was composed of a main effect ($984) and an interaction effect (
      $617). These findings have implications for substance abuse interventions and
      health care policy.

PMID- 11449749
TI  - The organization of service delivery. Overview.

PMID- 11449750
TI  - The outcome of treatment. Overview.

PMID- 11449751
TI  - Outcomes of alcohol treatment for adolescents.
AB  - The use by adolescents and young adults of alcohol and other drugs continues to
      be a tremendous problem for this nation. Over 30% of all high school students
      nationwide report episodes of hazardous drinking (five or more drinks on one
      occasion), when both moderate and heavy alcohol consumption are associated with a
      higher risk of alcohol-related medical consequences and accidental injuries for
      youth. Increased awareness and concern related to adolescent substance use has
      led to the outgrowth of additional treatment facilities and programs for this age
      group. The current chapter discusses how developmental factors may impact the
      assessment process and subsequent treatment for adolescent alcohol use disorders.
      In addition, outcome research, intervention studies, relapse, and factors that
      may influence the recovery process are discussed.

PMID- 11449752
TI  - Family-involved alcoholism treatment. An update.
AB  - We reviewed 36 randomized studies of family-involved treatment and comparison
      conditions. A meta-analysis showed a medium effect size favoring family-involved
      treatments, over individual treatment or wait-list, for outcomes of alcohol use,
      treatment entry/attendance, and family adjustment. Studies of family-involved
      treatment when the alcoholic is unwilling to seek help show: (1) Al-Anon
      facilitation and referral help family members cope better; (2) the popular
      Johnson intervention apparently does not effectively promote treatment entry; and
      (3) Community Reinforcement and Family Training promotes treatment entry and
      should be disseminated if replicated. Studies of family-involved treatment to aid
      recovery when the alcoholic has sought help show: (1) evidence supporting
      behavioral couples therapy (BCT) has grown considerably; (2) the disulfiram
      contract procedure should be disseminated as part of a BCT treatment package; and
      (3) studies of family systems and of family disease approaches are beginning to
      appear in the literature. Future studies need to include more women and minority
      patients and focus on children.

PMID- 11449753
TI  - The role of continuing care in outpatient alcohol treatment programs.
AB  - Substance-abusing patients are frequently urged to participate in continuing
      care, or "after-care," following an initial phase of treatment. However, there
      has been relatively little research on the effectiveness of continuing care,
      particularly in the context of outpatient service delivery systems. Since 1988,
      12 controlled studies of continuing care for alcohol use disorders have been
      published. Only three of these studies were conducted exclusively within
      outpatient service delivery systems; in the other studies, all patients (six
      studies) or at least half of the patients (three studies) were first treated in
      inpatient or residential facilities. Four of the 12 studies yielded positive
      findings (two of six studies with minimal/no continuing care control conditions
      and two of six studies with active control conditions). It is suggested that
      continuing care treatment might be improved by placing greater emphasis on
      addressing co-occurring problems and facilitating the identification and
      strengthening of patients' skills, interests, and talents, although additional
      research would be needed to evaluate the impact of these modifications. Further
      research is also needed to establish guidelines for when patients are ready to
      enter continuing care and to develop performance indicators to monitor progress.

PMID- 11449754
TI  - A comparative, process-effectiveness evaluation of VA substance abuse treatment.
AB  - Over 3,000 patients from 15 VA inpatient, substance abuse treatment programs
      showed considerable improvement from intake to a one-year follow-up. Patients in
      12-step programs, as opposed to cognitive-behavioral (CB) or eclectic programs,
      and those with more extended continuing outpatient mental health care and 12-step
      self-help group involvement, were more likely to be abstinent and free of
      substance use problems at follow-up. Consistent with their better one-year
      outcomes, patients in 12-step programs improved more between intake and discharge
      than CB patients on proximal outcomes assumed to be specific to 12-step treatment
      (e.g., disease model beliefs) and as much or more on CB proximal outcomes.
      Proximal outcomes assessed at treatment discharge and follow-up were, at best,
      modestly related to one-year substance use and other outcomes. No evidence was
      found that CB or 12-step treatment is more beneficial for certain types of
      patients.

PMID- 11449755
TI  - Screening and brief interventions for alcohol use disorders in managed care
      settings.
AB  - This chapter will focus on the identification and treatment of alcohol use
      disorders in general medical care settings in the context of managed care
      systems. The chapter will include the best data available on the prevalence of
      problem drinking, screening procedures, brief intervention ("talk therapy"), and
      implementation in managed care environments. The clinical protocols presented
      were designed for primary care clinicians working with patients seeking routine
      medical care. The protocol was developed for the National Institute on Alcohol
      Abuse and Alcoholism (NIAAA) Physicians' Guide. The four steps were designed to
      help clinicians to screen, to conduct a brief assessment, to provide advice and
      or referral and to establish follow-up procedures.

PMID- 11449756
TI  - The impact of managed care on substance abuse treatment: a problem in need of
      solution. A report of the American Society of Addiction Medicine.

PMID- 11449757
TI  - Effects of managed care on programs and practices for the treatment of alcohol
      and drug dependence.
AB  - Managed care is affecting the organization and financing of treatment services
      for alcohol and drug dependence. This paper examines the effects of managed care
      on program operations including the use of clinical protocols, the administrative
      burden, information systems, staffing, and program consolidation. It also reviews
      the effects of managed care on system performance related to employer-sponsored
      health plans, state employee health plans, and Medicaid and other public plans.
      Our review of managed care's influences on the alcohol and drug abuse treatment
      system finds evidence of systemic reductions in access to inpatient care and
      increased reliance on outpatient services. Moreover, although analyses of
      behavioral health carve-outs often suggest increases in the use of outpatient
      care, evaluations of substance abuse claims report reductions in ambulatory
      utilization for the treatment of alcohol and drug dependence.

PMID- 11449758
TI  - Linking clients to clinical and social services.

PMID- 11449759
TI  - Organizational and financial issues in the delivery of substance abuse treatment
      services.
AB  - Examination of organizational and financial characteristics of the specialty
      substance abuse treatment system allows an understanding of how to meet the needs
      of clients in the system. Further, this assessment may afford insights into how
      the specialty sector may adapt in the changing environment of managed care. Data
      from Phase I of the Alcohol and Drug Services Study (ADSS) describe the specialty
      substance abuse treatment system in terms of type of care, setting, level of
      affiliation, licensure/accreditation, ownership, revenue sources, client referral
      sources, client's primary substance of abuse, and managed care. Although the
      system is largely outpatient and remains substantially two tiered in terms of
      public/private funding mix, it varies along a number of organizational and
      financial dimensions which have implications for system structure and facility
      viability in the changing environment of substance abuse treatment service
      delivery.

PMID- 11449760
TI  - Access to alcohol treatment in the 21st century. Old worries and new optimism.
      Overview.

PMID- 11449761
TI  - [Reform the vaccination program for children!].

PMID- 11449762
TI  - [Use of blood from patients with hemochromatosis].

PMID- 11449763
TI  - [Time--a resource shorter than money!].

PMID- 11449764
TI  - [The status of physicians in charge of hospital departments].

PMID- 11449765
TI  - [More younger people on disability pensions].

PMID- 11449766
TI  - [More and more young people on disability pensions].
AB  - BACKGROUND: A considerable increase was noticed in Norway over the 1990s in the
      incidence of persons below 34 drawing disability pensions. In certain
      communities, the number almost tripled from 1992 to 1997. MATERIAL AND METHODS:
      In order to study the causes of this increase, we examined all applications for
      disability pension from persons below 34 in the years 1992 and 1997 drawn from 19
      selected local communities all over Norway, a total of 239 files. Social and
      medical variables and elements of the application procedure were registered and
      subjected to statistical analysis. RESULTS: Apart from the medical diagnoses
      used, there were only small differences between the characteristics of applicants
      in the two years under study. The number of persons with a psychiatric diagnosis
      was, however, considerably higher in 1997 than in 1992, in relative as well as in
      absolute terms. INTERPRETATION: We cannot say for certain whether the higher
      number of applicants registered with a mental disorder really reflects an
      increase in such disorders among young people, but the observations may reflect a
      higher incidence, probably caused by more pressure in the workplace in terms of
      competition and the level of qualifications required.

PMID- 11449767
TI  - [When time counts--hospital physicians' use of time and work assignments].
AB  - BACKGROUND: Various studies show that physicians spend less time with their
      patients and that their productivity is declining. This has raised questions
      about physicians' use of their time. MATERIAL AND METHODS: A total of 91
      physicians in the Department of Medicine and the Department of Women's Health at
      the University Hospital of Trondheim participated in a one-week registration of
      use of time and work assignments--a combination of field observation and self
      reported use of time. RESULTS: The physicians spent on average 60% of their time
      on clinically related assignments, 25% of this in direct contact with patients.
      However, there were great variations between physicians after controls had been
      made for selected organisational conditions. These variations indicate
      difficulties in using average scores of physicians' use of their time.
      INTERPRETATION: Work measurement is related to the organisational theory
      associated with the Scientific Management school of thought. It is not evident
      that this is a fruitful approach to ensuring effectiveness or to setting norms
      for expected use of time. The method does, however, provide a way of describing
      how physicians' work is organised.

PMID- 11449768
TI  - [Should school children receive pertussis vaccine?].
AB  - BACKGROUND: A study comparing diphtheria immunity in Norwegian and Russian
      schoolchildren indicated low immunity against diphtheria in Norwegian children
      before the booster dose given at age 11 years. The pertussis epidemic in Norway
      1997-98 demonstrated decreasing vaccine immunity from age 5-6 years. The
      possibility of improving immunity against both diseases by a booster dose during
      early school age is therefore under consideration. MATERIAL AND METHODS: Immune
      response and adverse events were studied after a combined vaccine against
      diphtheria, tetanus, pertussis (acellular) and poliomyelitis (DTPa-IPV) given at
      seven years of age, and a combined vaccine against diphtheria, tetanus and
      pertussis (acellular) (DTPa) at 11 years of age, in two parallel trials including
      124 and 83 participants respectively. RESULTS: The trials confirmed that the
      diphtheria immunity is lower than it ideally should be in more than 40% of
      children before the booster dose at age 11. Pertussis immunity is difficult to
      assess because there is no clear relationship between antibody levels and
      protection. All study participants responded well to all vaccine components. The
      11-year-old children reported higher occurrence of adverse events than the 7-year
      olds. All adverse events were brief and none were serious. INTERPRETATION: The
      results indicate that a booster dose of DTPa-IPV in early school age would give
      better protection against diphtheria and pertussis in Norwegian schoolchildren,
      without unacceptable side effects.

PMID- 11449769
TI  - [Duration of drug treatment in nursing homes].
AB  - BACKGROUND: This article deals with duration of and changes in drug treatment of
      nursing home residents. MATERIAL AND METHODS: The duration of the drug use of 117
      permanently admitted nursing home residents was studied retrospectively in five
      small nursing homes. All presently used drugs were registered with information on
      whether they were prescribed at or after admission. The drugs were recorded
      according to the ATC system. RESULTS: The median age of the residents was 87, the
      most frequent diagnoses were dementia (36%) and cardiovascular diseases (26%).
      There was a significant correlation between the number of drugs used and number
      of diagnoses (r = 0.35, p < 0.01). Drugs from ATC groups A and N were most
      commonly used. For all drugs except oestrogens there was a significant
      correlation between duration of stay and duration of treatment. Approximately
      three fourths of the residents taking cardiovascular drugs were treated at
      admittance. Two thirds or more of the use of laxatives, oestrogens, analgesics,
      psychotropic drugs and antihistamines were instituted during the nursing home
      stay. Antidepressants were prescribed relatively early after admittance,
      antipsychotics and anxiolytics later during the stay. INTERPRETATION: Major
      changes in drug use take place after admission to a nursing home. This especially
      applies to the use of psychotropics and diuretics which may precipitate the use
      of laxatives, while the increased use of analgesics and oestrogens may reveal
      under-treatment prior to admission. The drug use tends to be chronic.

PMID- 11449770
TI  - [Lamotrigine in the treatment of mental disorders].
AB  - BACKGROUND: Bipolar and other mood disorders often do not respond satisfactorily
      to lithium, valproate, carbamazepine or antidepressants. MATERIAL AND METHODS: On
      the basis of six years of clinical experience with lamotrigine in the treatment
      of psychiatric disorders, supplemented by three case reports and a comprehensive
      literature review of empirical studies, we discuss the possible indications for
      lamotrigine in psychiatric disorders. RESULTS: Lamotrigine seems to have a
      stronger antidepressant effect in bipolar 1 disorders than gabapentine,
      carbamazepine and valproate, but a weaker effect on manic symptomatology than the
      latter two. Lamotrigine may be of value in the treatment of bipolar 2 disorders
      in which chronic treatment resistant depression is often a complication,
      including rapid cycling and, in the unipolar version of rapid cycling, brief
      recurrent depression. We have also used to good effect the neuroprotective
      effects of lamotrigine in prophylactic treatment of neurodegenerative disorders
      (e.g. Huntington's chorea). INTERPRETATION: Lamotrigine is an anticonvulsant with
      an efficacy profile in psychiatric disorders different from those of valproate,
      carbamazepine and gabapentine. The drug represents an important supplement to the
      treatment options in chronic recurrent mood and neuropsychiatric disorders.

PMID- 11449771
TI  - [Anagrelide in primary thrombocythemia].
AB  - BACKGROUND: Essential thrombocythaemia is a chronic myeloproliferative disease
      characterised by persistent thrombocytosis, i.e. platelet count > 600 x 10(9)/l
      and an increased risk of thromboembolic complications. Anagrelide may be used as
      a platelet-lowering agent in patients with essential thrombocythaemia. MATERIAL
      AND METHODS: At Akershus Central Hospital, ten patients below 60 years of age
      have been treated with anagrelide in the period 1997 through 2000. Patients were
      identified and data obtained from hospital files. Nine patients had been treated
      previously, mainly with hydroxyurea. Three patients were asymptomatic. RESULTS:
      Anagrelide was introduced with gradually higher dosage, while the dosage of
      hydroxyurea was gradually reduced. Four patients experienced slight and transient
      headache, five palpitations, and two diarrhoea. One patient had to limit the dose
      because of palpitations. The medication was discontinued in two patients because
      of side effects. The seven patients who tolerated the medication well, acquired
      platelet counts below 500 x 10(9)/l. No vascular complications have occurred.
      INTERPRETATION: Anagrelide is an efficacious drug in essential thrombocythaemia
      with relatively few side effects. Anagrelide should be considered a treatment of
      choice in patients below 60 years of age with essential thrombocythaemia.

PMID- 11449772
TI  - [Symptoms and clinical course in carpal tunnel syndrome].
AB  - BACKGROUND: We wanted to study the symptoms in carpal tunnel syndrome, evaluate
      postsurgical median nerve recovery in elderly patients compared to younger
      patients, and investigate the clinical development and median nerve changes in
      non-operated cases. MATERIAL AND METHODS: The study included 92 patients
      diagnosed with carpal tunnel syndrome on the basis of clinical symptoms and
      neurophysiological findings. Neurophysiological data from elderly operated (70-89
      years), younger operated (30-69 years) and non-operated (25-83 years) patients
      were analysed separately. RESULTS: The most common symptoms were paresthesia in
      the third (97%) and second (88%) digits, nocturnal paresthesia (88%), increased
      symptoms when at work (78%), and pain in the hand (72%). Paresthesia in the
      entire hand (30%) and pain in the entire arm (55%) were common. Median nerve
      recovery in the elderly patients was comparable to the results in the younger
      operated patients. Some patients recovered clinically with normalisation of the
      median nerve without surgery. INTERPRETATION: Carpal tunnel syndrome will often
      have symptoms outside the median nerve territory. Elderly patients should be
      operated on the same indications as those applied to younger patients. Patients
      with no neurological findings may be monitored without surgery.

PMID- 11449773
TI  - [Can patients treated with therapeutic bloodletting become blood donors?].
AB  - BACKGROUND: Blood letting is an important form of treatment in some diseases,
      e.g. haemochromatosis and polycytaemia rubra vera. In our hospital, this
      treatment takes place in the blood bank. If the blood collected from these
      patients could be used for transfusion, it would help reduce the present blood
      shortage. MATERIAL AND METHODS: We examined the referral letters for all patients
      treated with blood letting during a twelve-month period in two hospitals to see
      how often the referrals gave information that would exclude the patient as a
      blood donor. RESULTS: 1,116 units of blood were collected from 177 patients. 122
      patients treated with 696 bloodlettings did have information in their referral
      letter which indicated that they would be unsuitable as blood donors. DISCUSSION:
      55 of 177 patients treated with blood letting could have been further evaluated
      in order to determine whether they fulfilled the criteria for blood donors. The
      impact of accepting patients as blood donors could be significant. Patients in
      need of blood letting are not voluntary, unpaid donors and additional steps are
      required to compensate for this fact.

PMID- 11449774
TI  - [With forceps all over the world--Christian Kielland and his forceps].
AB  - The history of the obstetric forceps is a colourful chapter in the history of
      medicine. Several hundred obstetric forceps have been described in detail, but
      most of them were minor modifications of the prototypes. However, the forceps
      invented by the Norwegian gynaecologist Christian Kielland (1871-1941) had a
      considerable impact upon the obstetric world during most of the 20th century.
      This ingenious instrument was demonstrated in Munich in 1915 and was gradually
      quite extensively used nearly all over the world. However, a great deal of
      controversy has surrounded his forceps, also in Norway.

PMID- 11449775
TI  - [Melatonin--use and misuse].

PMID- 11449776
TI  - [Does knowledge hurt?].
AB  - The rate of production of medical knowledge is high and increasing, and medical
      practitioners find it hard to keep up. Still, production of new knowledge is
      normally considered to be unambiguously desirable. This paper is a philosophical
      reflection upon this assumption of desirability. It is noted that the health
      sector appears to be subject to the law of diminishing returns; this implies that
      more doctors and more medical technology may at some level do more harm than
      good. We argue that Bacon's legitimization of knowledge (knowledge is power) is
      less forceful in the face of biological and psychosomatic complexity. Medical
      research may lead to unintended harm through at least two mechanisms. First,
      biomedical knowledge is reified through the introduction of new medical
      technology whose effects are not fully known, and may lead to uncontrollable
      adverse effects on a clinical and societal level. Second, exaggerated attention
      paid to the production and implementation of biomedical factual knowledge may
      prevent the development and teaching of personal clinical skills, including
      phronesis, the individual judgemental powers that enable us to judge which goals
      are worth striving for, and which are not.

PMID- 11449777
TI  - [Empathy in the physician-patient relation--tool or ethics?].
AB  - Empathy is a quality sought by patients, and an ideal that is pursued by the
      physicians themselves and in medical education. It is, however, necessary and
      important to define the boundaries between the concept of empathy and related
      concepts such as sympathy and compassion. This article is based on a study of
      literature addressing empathy and related concepts, and it attempts to illuminate
      the instrumental as well as moral significance of empathy in the physician
      patient relationship. The concept of empathy is seen as the ability to understand
      another person's situation, and is in itself morally neutral. Our capacity for
      empathy is based on emotional as well as intellectual skills. Empathy is
      primarily a mode of understanding that can be expressed by means of
      communication, but is not in its essence a form of conduct or behaviour. Empathy
      concerns the physician's fundamental attitude towards the patient and carries an
      independent moral value. It is part of the moral foundation of medicine and can
      be seen as a virtue in medical practice.

PMID- 11449778
TI  - [How do surgical teams train emergency surgical interventions?].

PMID- 11449779
TI  - [Antihypertensive agents, marketing and research].

PMID- 11449780
TI  - [Good research on impotence? Yes, please!].

PMID- 11449781
TI  - Genetic evaluation and counseling in head and neck syndromes.
AB  - Genetic diagnosis and counseling are dynamic areas of clinical medicine that must
      keep pace with the rapid advances in developmental and molecular biology.
      Identification of developmental pathways in primitive organisms has often led to
      the recognition of similar programs for development in vertebrates. An
      understanding of the function of genes studied in mice through knock-out and
      targeted mutation studies provides animal models for human dysmorphogenetic
      syndromes and candidate genes for human syndromes. As soon as a gene is cloned
      for a human disorder and mutations are identified in affected individuals,
      clinical applications in diagnosis, prediction, and prevention rapidly develop.
      Understanding how a gene functions and the consequences of its mutation will aid
      in counseling and will help determine prognosis. Some mutations that interrupt
      pathways early in development will cause malformations that are static or
      nonprogressive, as seen in PAX6 and Shh mutations. Others, such as FGFR
      mutations, will continue to interfere with normal morphogenesis throughout the
      period of growth and development in the regions affected by the mutated gene.
      Clinical geneticists and genetic counselors, by assuming responsibility for
      identifying individuals with or at risk for genetic disorders, serve as
      interpreters and guides to the options presented by this new technology.

PMID- 11449782
TI  - Neonatal care of infants with head and neck anomalies.
AB  - This article reviews the most common serious head and neck congenital anomalies
      and traumatic injuries that present at or around the time of birth from the
      perspective of neonatal caregivers. The focus is on the steps necessary to manage
      these infants in the delivery room and during the first days of life. An
      organized multidisciplinary team approach is critical to success.

PMID- 11449783
TI  - Cleft lip and palate.
AB  - The most common congenital deformity of the head and neck, cleft lip and palate,
      presents the surgeon with a unique esthetic and reconstructive challenge. The
      complexity of these deformities demands the skills of a multidisciplinary team of
      professionals to optimize surgical outcome. This article discusses the
      embryology, epidemiology, and genetics of cleft lip and palate and details the
      history and modern methods of their surgical correction, the proper goal of which
      is restoration of normal facial form and velopharyngeal function.

PMID- 11449784
TI  - Velocardiofacial syndrome.
AB  - Velocardiofacial syndrome is one of the most common multiple-anomaly syndromes in
      humans. With its many otolaryngologic manifestations and its almost ubiquitous
      effects on speech, language, hearing, immune dysfunction, and airway problems,
      velocardiofacial syndrome may be the most common genetic disorder seen by
      pediatric otolaryngologists. Individuals affected with velocardiofacial syndrome
      look essentially normal making identification of the syndrome difficult,
      especially in infants. It is critical for otolaryngologists to be familiar with
      the symptom complex associated with velocardiofacial syndrome so as to understand
      the unique manifestations of this complex disorder.

PMID- 11449785
TI  - Maxillofacial pathology and management of Pierre Robin sequence.
AB  - Pierre Robin sequence affects 1:8500 newborns and is characterized by cleft
      palate, micrognathia, and airway obstruction. Evolution in the understanding of
      the causes and pathogenesis of this condition is reviewed. Clinical findings and
      treatment options are also addressed. An overview of syndromes commonly
      associated with Pierre Robin sequence is provided.

PMID- 11449786
TI  - Syndromes involving craniosynostosis and midface hypoplasia.
AB  - This article reviews a number of well-known syndromes involving craniofacial
      synostosis and associated midface deficiencies. Syndromes discussed include
      Apert's, Crouzon's, Saethre-Chotzen, and Carpenter's. Clinical characteristics
      and genetic defects are discussed. A general approach to surgical management is
      outlined.

PMID- 11449787
TI  - Otolaryngologic manifestations of Down syndrome.
AB  - The DS patient has clear anatomic differences in the head and neck region when
      compared with the general population. These anomalies include a flat occiput,
      oblique palpebral fissures, epicanthal folds, speckled irides, a protruding
      tongue, prominent malformed ears, and a flat nasal bridge. Congenital otologic
      anomalies and acquired conditions such as otitis media are also more frequently
      observed in the DS population. The DS patient is predisposed to obstructive sleep
      apnea, and the diagnosis of sleep apnea in DS patients is more likely to be
      delayed. A child with DS who has a narrowed nasopharynx, large tongue, and a
      subglottis which is smaller than normal must be given special consideration at
      the time of intubation. Such a patient requires an endotracheal tube two sizes
      smaller than the standard size appropriate for the patient's age. The child
      should also be suspected of having and be evaluated for obstructive sleep apnea,
      to ensure that appropriate precautions are taken in the perioperative period.
      Finally, any DS patient undergoing preoperative evaluation for a general
      anesthetic should have a careful assessment of the cervical spine to avoid
      dislocation or spinal cord injury. Hearing loss may be suspected in any
      congenital syndrome. In DS, there is a clearly increased incidence of congenital
      temporal bone anomalies, external auditory canal stenosis, and otitis media. All
      DS patients should undergo hearing assessment in the neonatal period, with follow
      up as appropriate. Aggressive treatment of conductive hearing loss and early
      amplification may be necessary to maximize speech and language development.

PMID- 11449788
TI  - Congenital laryngeal anomalies. Laryngeal atresia, stenosis, webs, and clefts.
AB  - Congenital laryngeal anomalies may occur as a result of defects in normal
      prenatal development. They are associated with a broad spectrum of symptoms and
      require treatment ranging from observation alone to complex open airway surgery.
      The treating otolaryngologist must organize a management strategy focused on
      timely diagnosis, ensuring a safe airway, and maximum conservation of
      respiratory, phonatory, and swallowing ability.

PMID- 11449789
TI  - Head and neck anomalies related to the branchial apparatus.
AB  - An understanding of the branchial apparatus and its anomalies may lead to greater
      precision in the clinical diagnosis and management of these congenital head and
      neck lesions. Although branchial anomalies have been well described,
      controversial issues, such as the branchial origin of lateral cervical cysts and
      the differentiation between third and fourth branchial pouch sinuses, remain
      unresolved.

PMID- 11449790
TI  - Head and neck manifestations of cystic fibrosis and ciliary dyskinesia.
AB  - Cystic fibrosis and the various conditions associated with ciliary dysmotility
      are well known to the otolaryngologist. Although the underlying pathophysiology
      and clinical courses of these diseases are quite different, they both involve
      chronic and acute infection in the paranasal sinuses. Some patients may suffer
      from persistent ear disease beyond early childhood. A high index of suspicion and
      early diagnosis are key to managing these conditions. The otolaryngologist often
      is the first to suspect and confirm the diagnosis and may have an important role
      in the overall management of these patients.

PMID- 11449791
TI  - Choanal atresia, CHARGE association, and congenital nasal stenosis.
AB  - Congenital bilateral narrowing or obstruction of the nasal airway can result in
      significant respiratory distress in the neonate, requiring emergency
      intervention. Some of these children have associated congenital malformations
      that may also impact on the management of the nasal anomaly. The embryology,
      presentation, and management of this spectrum of disorders are discussed, and the
      major surgical controversies are reviewed.

PMID- 11449792
TI  - The team approach to treating the microtia atresia patient.
AB  - For optimal function and esthetic results in the microtia/atresia patient, an
      integrated team approach between the plastic surgeon and the otologic surgeon is
      essential. This article addresses this complex management problem by drawing on
      the author's experience with more than 1000 microtia patients. This article
      elucidates an optimal strategy for integrated patient care that has been
      developed in conjunction with several experienced otologists over the past 25
      years.

PMID- 11449793
TI  - Genetics and molecular biology of deafness. Update.
AB  - This article discusses the latest research in the molecular biology and genetics
      of hearing impairment and its importance to otolaryngologists. Recent research
      has led to the discovery of many of the genes and gene products that are
      responsible for hereditary hearing impairment. State mandated screening of
      newborn infants for hearing loss ensures that a large number of hearing-impaired
      children will be detected at a very early age. Additionally, these children often
      will be referred to the otolaryngologist for evaluation of the hearing
      impairment. It is the otolaryngologist who must gather a detailed family history
      and perform a thorough physical examination to fully assess the cause of the
      hearing impairment. In taking the family history, it is important to note that
      the diagnosis of a hereditary hearing impairment often involves the evaluation of
      a large-sized family that has a history of hearing disorders. A history of an
      affected individual in a small family does not necessarily support a diagnosis of
      hearing impairment in later affected offspring because of the small sample size.
      Often, a hearing impairment that is part of a syndrome may not be detected
      because the physical findings associated with a syndrome are subtle in a young
      infant. For example, the white forelock seen in patients with Waardenburg's
      syndrome type I cannot be visualized in the infant who lacks hair. Additionally,
      some patients with syndromic hearing impairment do not present with physical
      findings, but rather they exhibit abnormal laboratory studies. Additional points
      to remember include the following: As infectious iatrogenic causes of hearing
      impairment decrease, the relative incidence of hereditary hearing impairment will
      increase. Hereditary hearing impairment can present as an isolated finding, or in
      association with a number of anomalies recognizable as a syndrome. The study of
      genetics and molecular biology has led to the identification of genes associated
      with hearing impairment and will allow for future screening and possible therapy
      for the hearing-impaired. The screening of newborns for hearing impairment using
      the techniques of molecular biologists and geneticists will result in early
      identification and appropriate intervention for those at risk for hereditary
      hearing impairment. An understanding of the syndromic and nonsyndromic causes of
      hereditary hearing impairment can help the otolaryngologist make a diagnosis and
      provide appropriate audiologic and educational management to the patient.

PMID- 11449794
TI  - [Regulation of extracellular phosphohydrolase biosynthesis in bacilli].
AB  - Under phosphate-deficient conditions, B. intermedius, B. pumilus, and B.
      thuringiensis secrete phosphohydrolases, including phosphomono-,
      phosphodiesterases, and guanyl-specific ribonucleases which cleave RNA molecules
      to nucleoside-3'-phosphatases. The enzymes are synthesized by phosphate-starved
      vegetative cells, which is not associated with sporulation. Using B. subtilis
      strains with mutation in the regulatory protein genes phoP and phoR, it was shown
      that these proteins regulate expression of B. intermedius, B. pumilus, and B.
      thuringiensis ribonuclease genes in B. subtilis cells. Genes of heterologous
      RNAses were activated in recombinant B. subtilis strains simultaneously with its
      own PHO regulon genes. Presumably a regulatory system homologous to B. subtilis
      two-component PhoP-PhoR signal transduction system functions in other
      representatives of the Bacillus genus.

PMID- 11449795
TI  - [Use of phage display for detecting single-nucleotide differences in genes].
AB  - Experimental strategy has been developed for selection of mismatched DNA binding
      phages from library of E. coli f1 filamentous phages carrying random peptide
      inserts on the surface of bacteriophage particles. The strategy is based on the
      use of phage display technique, DNA heteroduplexes (with single nucleotide
      variations), and paramagnetic beads. DNA heteroduplexes have been obtained from
      biotin-labeled PCR product. During the first stage the phage particles were
      incubated with DNA heteroduplexes possessing mismatched nucleotides. The next
      step after elimination of free phages and separation of bound phages from DNA
      heteroduplexes was subtraction of phages binding with DNA heteroduplexes (without
      mismatched nucleotides). Phages selected by this method were capable of
      discriminating DNA heteroduplexes with single nucleotide variations from DNA
      homoduplexes. Phages immobilized on solid base retain their activity and
      specificity, and therefore can be used for developing a new screening automated
      method for detecting point mutations and gene polymorphism.

PMID- 11449796
TI  - [PCR-detection of markers for epidemiologically-significant strains of Vibrio
      cholerae 0139, isolated in Siberia].
AB  - Fourteen V. cholerae 0139 strains were isolated in 1996-1999 in Siberia from the
      Ob river (Novosibirsk) and bogs and lakes (Irkutsk). The strains were tested in
      PCR for the key virulence determinants (ctx AB, tcp, acf). The genomes lacked
      these elements, and therefore the strains were acknowledged avirulent. The
      results correlate completely with the data of phenotypical analysis,
      characterizing the pathogenic characteristics of isolated strains.

PMID- 11449797
TI  - [Comparative analysis of the immune response of a rabbit to antigens to live and
      killed Francisella species bacteria].
AB  - Serum antibodies were analyzed in rabbits immunized with live and formalin-killed
      Francisella (F. tularensis, F. novicida, F. novicida-like, and F. philomiragia).
      Passive hemagglutination test with erythrocytes sensitized by these bacteria' LPS
      showed much higher titers of species-specific antibodies in all sera to live
      microorganisms than sera to killed bacteria. The results of immunoblotting with
      purified LPS and bacterial lysates indicate that sera to live bacteria contained
      mainly immunoglobulins to species-specific antigenic epitopes of LPS O
      polysaccharide chain and few antibodies to the protein component of the cell. By
      contrast, killed bacterial cells induced weak production of antibodies to S-LPS
      and a pronounced antibody response to protein antigens. Besides the quantitative
      differences, live and killed bacteria differed by the qualitative spectrum of
      immunodominant proteins. Serum to live F. tularensis 15/10 contained antibodies
      to at least 3 immunodominant antigens of the cell, while serum to killed bacteria
      contained antibodies to only two of these. Immunoglobulins to protein antigens,
      absent in homologous sera to live bacteria, were detected in the sera to killed
      F. novicida and F. novicida-like bacteria. Both sera to F. philomiragia had
      antibodies reacting with LPS epitopes and immunodominant complex containing
      protein. In contrast to other Francisella, F. philomiragia was found to
      synthesize an uncommon LPS representing two major lipooligosaccharides with
      different molecular weights and antigenic specificity. Therefore, immune response
      of the host to live and killed Francisella is different: live cells more
      effectively induce the production of antibodies to S-LPS epitopes, while killed
      ones to protein antigens.

PMID- 11449798
TI  - [African swine fever virus: achievements over the last decade of the 20th
      century].
AB  - Complete nucleotide sequence of African swine fever (ASF) virus genome was
      determined in 1993-1999. Deletion mutants with low virulence for pigs were
      obtained. Genes of structural (p72, p54, p12, cleavage products pp220 and pp60,
      hemagglutinin) and nonstructural (p32) proteins were mapped. The significance of
      different proteins in virus adsorption and resistance to challenge was
      elucidated, their location in infected cell and virion was determined. Lipid
      composition of the virus was studied. A protocol of virion morphogenesis was
      suggested, which explains their morphology. Apoptosis, consumption coagulopathy,
      and development of delayed type hypersensitivity are regarded as the main
      pathogenetic mechanisms. Antigens acting as targets and inductors of immune
      cytological reactions and antibodies mediating suppression of virus reproduction
      were determined.

PMID- 11449799
TI  - [Isolation of canine rotavirus and study of its immunobiological properties].
AB  - Canine rotavirus was isolated in MA104 roller culture of rhesus macaque cells.
      Two passages in gnotobiotic puppies and two in colostrum-free puppies resulted in
      isolation of strain P of canine rotavirus. After 20 passages in MA104 culture the
      virus was adapted to MDCK culture. Optimal conditions for accumulation of canine
      rotavirus and its antigen (9.01 g TCD50/ml) in MDCK culture are trypsin
      pretreatment of the virus inoculate in the final concentration of 50 mcg/ml for
      30 min at 37 degrees C, presence of trypsin (10 mcg/ml) in the maintenance
      medium, multiplicity of infection 0.1 TCD50/ml, and incubation in roller culture
      at 37 degrees C during 24-30 h. After 60 passages in cell culture, canine
      rotavirus completely lost its virulence for colostrum-free puppies but retained
      antigenic activity and induced manifest seroconversion in infected.

PMID- 11449800
TI  - [Development and preparation of recombinant gD antigen of the herpes simplex type
      1 (HSV-1) virus].
AB  - The most potent antigen among HSV-1 proteins are glycoproteins gB(UL27) and
      gD(US6). Multiple amino acid sequence alignment of these proteins shows that gD
      protein is the most specific for HSV-1. Analysis of gD protein epitopes detected
      the main antigenic determinants not cross-reactive with antigens of other
      viruses. Virus was isolated and genome DNA was prepared from morphological
      elements of a patient with herpes simplex infection. US6 gene fragment was cloned
      in pUC19 vector. Cloning in bacterial expression vectors helped obtain beta
      galactosidase-fused recombinant HSV-1 gD protein with 6-histidines affine target
      for high-performance chromatography purification. ELISA with a set of HSV-1
      positive and negative donor sera and a commercial panel of HSV-1 sera (Vektor
      Best) showed that recombinant gD can be used as an antigen to HSV-1-specific IgG.

PMID- 11449801
TI  - [An antigen related to the mouse mammary cancer virus env gene product, detected
      in human lymphocytes, is associated with human breast cancer].
AB  - Expression of DNA sequences homologous to sequences of env gene of mouse mammary
      tumor virus (MMTV) in the lymphocytes of patients with breast cancer and in
      subjects at a high risk of breast cancer has been reported. Antigen analogous to
      envelope protein gp52, product of MMTV env gene, is detected in T lymphocytes of
      virtually all patients with breast cancer and extremely rarely in T cells of
      controls, where its expression is confined to B cells. For explaining such
      unexpected results, we studied the molecular basis of this antigen synthesis.
      Specific PCR products were obtained using primers to gp52-coding region of MMTV
      env gene. One of them (957 nucleotides) was used as a probe for hybridization of
      DNA and RNA from lymphocytes of patients with breast cancer and controls. This
      sequence was hybridized with 90% frequency with genome DNA of breast cancer
      patients and with 85% frequency with genome RNA of such patients, which is almost
      4-fold more than in the controls (patients with gynecological tumors or donors).
      These results correlate with the frequency of detection of the studied antigen in
      patients with breast cancer and control group patients.

PMID- 11449802
TI  - [Isolation and functional-structural characteristics of Bacillus polymyxa
      RP4::Mucts62 transcipients].
AB  - Conjugative-like transfer of hybrid plasmid RP4::Mucts62 from Escherichia coli to
      plasmid-free Bacillus polymyxa was carried out. Bacillus transcipients are
      detected by the markers of kanamycin and tetracyclin resistance RP4 and thermal
      sensitivity to growth at 40-42 degrees C, determined by prophage Mucts62 in the
      plasmid. The technique of transception using millipore filters on solid media has
      been improved. For comparison with experimental samples, restriction mapping of
      the native plasmid in donor E. coli GA570 strain was carried out with
      identification of the prophage location in point 30.5 n. p. of RP4 map with
      counter-clockwise orientation of the right terminal towards IS21 element. Two
      phenotypes of bacillus transcipients selected for restriction mapping were
      singled out. Phenotype KmRTcRTS retains all markers of donor strain plasmid, and
      by the sum of restricts electrophoretically either corresponds to intact hybrid
      plasmid or contains deletions in RP4 sites (1-8 n. p.) adjacent to the left arm
      of prophage or rarely on the right arm (up to 3 n. p.). KmRTcRTS transcipients
      lose kanamycin resistance and on restriction map show greater prolongation of
      deletions from the prophage right terminal to kan RP4 gene, shortening it to 13
      n. p. without involving the prophage proper. Its left terminal is retained, but 2
      7 n. p. sites are deleted in the RP4 area adjacent to it. The possibility of
      transception in nature and horizontal routes of drug resistance dissemination
      among genetically remote bacteria are discussed.

PMID- 11449803
TI  - Child and adolescent psychiatry and family therapy. An overview.
AB  - This article has provided an overview of the complex relationship between family
      therapy and child and adolescent psychiatry. Emphasis has been placed on the fact
      that the controversy and polarization that earlier characterized the relationship
      have delayed, but not blocked, the full integration of family therapy into child
      and adolescent psychiatry. Child psychiatrists and family therapists have been
      able to move beyond dichotomous polemics to combine the two fields in clinical
      practice, which has led to meaningful convergence in research and services.
      Family research has yielded important new directions for clinical practice in the
      areas of attachment, alcoholism, conduct disorder, and schizophrenia spectrum
      disorders. It also has led to models of family continuity that have considerable
      potential for interrelating and possibly integrating different family therapy
      models. Family research also has uncovered family factors in the
      intergenerational transmission of psychopathology that can inform clinical
      practice. Convergence in the clinical domain has led to improved assessment and
      treatment across a wide range of child, adolescent, and family developmental,
      emotional, behavioral, and mental disorders. Finally, this article has reviewed
      the controversy over family systems therapy and the development of new directions
      in theory and practice to which this controversy has led. Despite the possibility
      that these new directions might lead to significant disruption and interference
      in the process of convergence, careful examination of the controversy and the new
      developments in practice suggests that rather than producing division between the
      two fields, the new developments, especially narrative therapy, are more likely
      to bring the two fields closer, particularly in the realm of interventive
      interviewing in family therapy.

PMID- 11449804
TI  - Assessment of the family. Systemic and developmental perspectives.
AB  - Why was Elizabeth the symptomatic family member? This challenging question is
      informed by the family assessment, which examines family process patterns, family
      structure, family history, and developmental challenges of individual family
      members and the family as a whole. Although the answer to this question may never
      be explained completely, the family assessment does contribute to the
      biopsychosocial formulation on which rational therapeutic intervention is based.
      The family assessment does not replace a clinical assessment of the identified
      patient. Rather, the use of the family assessment provides a greater breadth from
      which to view children and adolescents presenting complaints.

PMID- 11449805
TI  - The integration of individual therapy and family therapy in the treatment of
      child and adolescent psychiatric disorders.
AB  - Children influence families and families influence children. Individuals create a
      family, and a family is more than a sum of its individuals. These dialectic views
      are at the heart of the clinical application of the integration of individual and
      family therapy. Any attempt to treat the mental disorders of children and
      adolescents must consider both views and their treatment implications. The use of
      combined therapeutic modalities can offer more flexibility, specificity, and
      precision for the treatment process.

PMID- 11449806
TI  - Parent management training.
AB  - As the estimates of prevalence and cost of mental health problems in our children
      continue to rise, it is incumbent on our society to have an effective and cost
      efficient means to address this health crisis. Consistently, the research
      literature indicates that PMT offers great promise as an efficacious treatment of
      conduct-disordered children. There are recent studies of PMT's benefits as a
      preventive intervention that not only improves children's conduct but also
      positively affects parent-child relationships, mood, social competence, and
      school adjustment or performance. Although relatively untested, there are
      indications that PMT also could play an important adjunctive role in the
      treatment of internalizing disorders. As a curriculum-driven and didactic form of
      treatment, PMT is highly adaptable to various treatment and prevention contexts,
      and from a managed care perspective, PMT's structure allows its costs to be well
      defined and managed. Despite these positive attributes, however, few clinics
      systematically offer PMT as a treatment option, and third-party payers have been
      reluctant to cover its costs. Although it is conceded that much needs to be
      learned about the scope of PMT's effectiveness and the modifications that are
      necessary to improve its adaptability to high-risk families, it is proposed that
      PMT should join the mainstream of broadly available health care provisions for
      children and their families. This broad inclusion of PMT requires mental health
      educators to include PMT training as a standard part of provider training,
      requires that third-party payers include PMT as a covered service, and requires
      that local and federal governments support the proliferation of PMT in treatment
      and prevention initiatives.

PMID- 11449807
TI  - Attachment and depression. Implications for family therapy.
AB  - The preceding discussion highlights the use of attachment theory in
      conceptualizing the interface between normal development and the manifestation of
      depression from infancy through adolescence. Additional research is needed to
      delineate better the specific nature of the association between attachment
      relationships and depression, particularly with regard to factors that mediate
      and moderate the link. The extant literature informs family-oriented clinical
      interventions with depressed young people with comorbid attachment problems, with
      or without a depressed parent. These family interventions are most likely to be
      effective if they incorporate developmentally informed conceptualizations and
      techniques and are targeted specifically to the problems of depressed youth and
      their families. The efficacy of such interventions remains to be determined
      through the implementation of treatment efficacy and effectiveness studies.

PMID- 11449808
TI  - Relationship disturbances and parent-child therapy. Sleep problems.
AB  - This article has attempted to establish the importance of considering behavioral
      disturbances in infancy and early childhood as disturbances of the parent-child
      relationship. When the psychologic and mental mechanisms of the individual infant
      are too immature to sustain disturbed behavior across several settings and when
      the behavioral disturbance seems to be specific to a particular relationship, it
      is more appropriate to diagnose the pathology as being in the relationship. The
      article has offered a diagnostic framework of relationship pathology that spans
      the spectrum from normal variation (relationship perturbation) to relationship
      behaviors that are at risk of becoming a disorder (relationship disturbance) to
      significant relationship disorders that most likely require a professional
      intervention. A multiaxial assessment protocol is recommended that evaluates
      primary relationships (Axis I), parent-infant interaction styles (Axis II), the
      parent and infant as individuals (Axis III), and more distal contextual factors
      that affect the relationship (Axis IV). Sleep disturbances in infancy have been
      used as an example to demonstrate the spectrum of relationship pathology.
      Additional research is needed to develop more precise, age-relevant cut points
      for the spectrum of relationship pathology for sleep problems and for other
      parent-infant relationship disturbances in the areas of feeding, excessive
      crying, and limit setting or tantrums. More research is also needed to define
      better when and how relationship pathology becomes transformed into individual
      pathology and how early intervention may alter the course of this trajectory.

PMID- 11449809
TI  - Family therapy for conduct disorders.
AB  - Low levels of parental skill and cooperation are the prominent roots of arrested
      socialization, and a lack of appreciation for intimate and gratifying human
      relationships is evident in children with CD. The relational problems are
      exaggerated further by the child's observation of chronic parental discord and
      internalization of a family image constructed around intrafamilial conflict and
      isolation. Skills deficits in parental and marital communication and problem
      solving and conflicts in these relationships play significant roles in producing
      family dysfunction. The low level of parental differentiation and identity
      formation plays a fundamental role in family dysfunction by interfering with the
      development of an adequate self-image, self-esteem, and internal codes of
      behavior in the child. The transmission of parental antisocial tendencies to
      their children is facilitated by the low level of differentiation between parent
      and child. Family treatment should focus on enhancing cooperation between parents
      and children and between parents as co-parents and as a couple. Enhancing parent
      management skills can undermine the use of coercive, punitive, and impulsive
      interactions in the families. The higher divorce rate in parents of children with
      CD should be addressed with parents directly and early in treatment with the hope
      of mobilizing the rehabilitative and cooperative marital forces. In terms of
      future directions, family studies should address and incorporate the expanding
      knowledge of biologic and psychologic characteristics of children with CD and the
      possible impact of such characteristics in undermining family development and
      integrity. Such investigations should include the following information: The role
      of sustained and intense aggression in some children on family functioning and
      development. The possible role of diminished response to punishment and excessive
      search for gratification in children with CD. The role of the child with CD in
      promoting marital and family discord and divorce. The role of neurotransmitters
      (such as serotonin) in the production of irritability, provocativeness, coercive
      family processes, and subsequent depression in the caregiver or the child.
      Effective models of intervention with children with CD in hospitals and
      residential treatment centers.

PMID- 11449810
TI  - Family therapy for eating disorders.
AB  - It is a perpetual source of debate whether dysfunctional family communication and
      relationship patterns cause eating disorders or the stress associated with
      raising a child with an eating disorder elicits such problems. Regardless, family
      therapy is a necessary component of any comprehensive biopsychosocial approach to
      the treatment of eating disorders. A careful assessment of the entire family,
      including the identified patient; his or her parents and siblings; the parents'
      marriage and families of origin; the child's emotional, social, and physical
      development; parental regulation of developmental stages; and communication
      patterns is mandatory. Family therapy for eating-disordered patients attempts to
      facilitate the elimination of potentially life-threatening symptoms and begin a
      therapeutic process of change within the entire family. Research has shown
      significant support for the use of family therapy in this population, but well
      controlled treatment outcome research remains somewhat limited.

PMID- 11449811
TI  - Physically manifested illness in children and adolescents. A biobehavioral family
      approach.
AB  - This article presents a family systems approach to the assessment and treatment
      of children and adolescents with physically manifested illness. A biobehavioral
      continuum of psychologically and physically manifested disease is offered to
      replace the false dichotomy of organic versus psychological illness. The
      Biobehavioral Family Model, an empirically validated model of the mutual
      influence of family relational patterns and childhood illness, organizes the
      treatment approach. The Family Process Assessment Protocol provides a method of
      diagnosing the child's illness in the context of family relational functioning.
      Two cases, a child with conversion disorder and a child with asthma, illustrate
      this approach. Additional family systems approaches are referenced in a table
      with citations.

PMID- 11449812
TI  - Consultation with the extended family. Primary process in clinical practice.
AB  - In this article, the authors have attempted to describe a method from their
      pattern of experiential family psychotherapy and to demonstrate its usefulness.
      Consultations with the extended family serve many purposes, but the one the
      authors highlight is the way they provide access to the unconscious components of
      the family. The extended family consultation interview is like an emotional hot
      tub that precipitates what the authors call a family group psychosis, an
      inherently therapeutic experience.

PMID- 11449813
TI  - Variations in family composition. Implications for family therapy.
AB  - The American family is truly diverse, with many forms and changes between and
      among forms common. Each variation in family composition presents its own unique
      challenges and possesses its own unique possibilities for success, building on
      its own unique strengths. Each family in trouble expects and demands respectful,
      patient, and committed assistance from the family therapist. The family therapist
      must appreciate the uniqueness of an individual family and the features that that
      family has in common with similar families and with all families. It is the
      commitment of parental figures to take responsibility for their children and
      participate actively with them in their development that creates successful
      family life. The family therapist's acceptance, curiosity, and respect for the
      family and its members encourages change and enlists strengths. This approach
      permits the family therapist to participate in meaningful and effective lives for
      each family.

PMID- 11449814
TI  - Culture and family therapy.
AB  - Children and families constitute an ever-increasing culturally diverse group in
      this country. Together with incentives in multicultural education and the
      evidence of the impact of different cultural values in the media, these groups
      have become more visible, more complex, and harder to study. Culture is defined
      as dynamic and expressive of shared values and behaviors. Cultural patterns may
      be situation specific and change according to contextual demands (rural versus
      urban youth) or may be population specific (the culture of gay youth versus
      heterosexual youth). Some people also ascribe to cultural beliefs, but these do
      not necessarily translate to behaviors. Families and their children vary in their
      level of acculturation and developmentally vary in their level of ethnic
      identification. Child-rearing patterns and parenting approaches are constantly in
      flux, as are gender roles and, increasingly, religious affiliations. Clinicians
      are challenged to treat these families and often find the cultural dissonance
      with their own native culture and theoretical approaches as obstacles for the
      appropriate assessment and treatment interventions. As the field of family
      therapy has developed, so have culturally sensitive and competent approaches in
      the field of mental health. These approaches must be integrated into the
      multiplicity of other factors that define normality and psychopathology and be
      studied further in the context of their relevance and efficacy for special groups
      of children and families who suffer with specific disorders. In the meantime,
      cultural awareness and competence will continue to help clinicians understand
      better the impact of values and patterns in family cycles, family organization,
      child-rearing practices, and the expression of symptoms in family systems.

PMID- 11449815
TI  - Children in families in communities.
AB  - While acknowledging valuable principles of serving children in their own
      communities, children's services continue to be disruptive to children and
      families' relationships within their communities. The long-term effects of these
      disruptions may be reflected in chronic displacement, maladjustment, and
      adaptation to institutional mores. Involving families and accessing communities
      in serving children increases healthy adaptation by helping children establish
      roles, establish membership, and contribute to their communities' life as they
      mature. Although community-based services have the benefit of trying to keep
      children in their communities, most programs do not go far enough to involve the
      community in assuming responsibility for these children. Approaches that
      facilitate family collaboration with community agencies (such as schools), move
      farther in this direction. Projects focused on stimulating community leadership
      to change community life to include youngsters in constructive roles offer the
      best hope of establishing systems that foster healthy outcomes for children and
      families in the long run.

PMID- 11449816
TI  - The biology of family psychotherapy.
AB  - This article has presented a view of biologic psychiatry consistent with that
      described by Bowlby, discussed hypotheses concerning the biologic purpose of the
      primate brain and the human brain, and challenged standard beliefs about the
      identity of the patient entity in a true biologically based psychiatry. Ideas
      developed by Whitaker, Malone, and their colleagues almost 50 years ago are
      consistent with a modern biologic basis of family psychotherapy. The treatment of
      an anorexic family was used to illustrate possible mechanisms of
      psychotherapeutic treatment requiring the presence of the whole family. The role
      of the psychiatrist who treats a family is to understand the biologic or medical
      importance of treating the family as a whole, communicate this to the family,
      continually work toward that level of participation, suggest relevant topics for
      discussion, and catalyze interactions within the family. Psychotherapy with
      families as a whole is effective because of the power of kin selection and
      inclusive fitness, biologic processes not usually considered in the practice of
      medicine or psychiatry.

PMID- 11449817
TI  - Current status of family intervention science.
AB  - Looking at the field as a whole through metaanalysis, Shadish et al concluded
      (based on 162 studies) that marital and family therapies were significantly more
      effective than no treatment and at least as effective as other forms of
      psychotherapy. Although these reviews and others are positive, individual studies
      raise many questions. For instance, based on research findings, family treatments
      increasingly have become standard care for patients with schizophrenia. It
      remains unclear what degree and type of family involvement is needed for which
      patients at which stage of their disorder. In the area of anxiety and depression,
      there are too few studies to make any strong conclusion. Although investigators
      such as Barrett, Cobham, and Diamond have produced some positive results, the
      Lewinsohn and Clark studies fail to demonstrate the added benefit of family
      involvement. Although Brent's study showed CBT to reduce depression faster,
      family therapy and supportive therapy did just as well in the long run, and
      family conflict was a strong risk factor for relapse. In the area of anorexia,
      Russell and Robins produced strong results from family interventions, whereas
      Geist found no difference between different types of family interventions. Family
      treatments for obesity have been inconsistent. In a metaanalysis of 41 studies,
      parental involvement did not contribute significantly to outcomes. In the Epstein
      study, however, which included 5- and 10-year follow-up, the results of family
      intervention were impressive. Although many of these studies can be cited for
      various methodologic flaws, the most consistent problem is that sample sizes are
      too small to detect difference between two or more active treatments. The most
      consistent findings (and most well-done, large studies) that support the efficacy
      of family-based interventions are done with externalizing problems. Work groups
      led by Patterson, Eisenstadt, Webster-Stratton, Alexander, and Henggeler all have
      produced impressive reductions of oppositional and antisocial behavior. Clinical
      programs that treat these populations without using a family-based intervention
      as at least a component of a treatment package are seriously ignoring the
      findings of contemporary intervention science. Programs of research by Henggeler,
      Szapocznik, and Liddle demonstrate similarly impressive results for substance
      abusing adolescents. Although preliminary results from the Dennis et al study
      suggest that various treatment approaches may benefit this population. Family
      interventions have had less success in reducing ADHD symptoms, yet these
      psychosocial treatments have been essential in reducing much of the family and
      school behavior problems associated with this disorder. Many investigators would
      agree that a combined medication and family treatment approach may be the
      treatment of choice for children with ADHD. In fact, many studies across various
      disorders suggest that patients respond best to comprehensive treatment packages,
      of which a family treatment is at least one component. Although the data are
      promising, many challenges lie ahead. Although collectively many family
      intervention studies exist, many disorders lack enough rigorous and large-scale
      investigations to make any strong conclusions. Kazdin argues that sample sizes of
      150 are essential to detect significant differences between active treatments,
      and few of the reviewed studies include these kinds of patient numbers.
      Furthermore, not enough committed and sophisticated family treatment researchers
      have carried out some of the major studies. For example, the Brent study on
      depression and the Barkley study of ADHD, although testing family approaches,
      lacked well-developed and published treatment manuals, a demonstration of the
      necessary expertise to supervise these treatments, and data about training and
      adherence to these models. Although the absence of expertise limits investigator
      allegiance biases, treatment development and modification are essential for
      tailoring family treatments to target family processes specific to each disorder.
      Investigators such as Patterson and Liddle have invested great effort in
      rigorously dismantling the treatment process, identifying and refining essential
      ingredients, and repackaging more potent treatment protocols. This process has
      paid off well. Programmatic treatment development is needed for many disorders to
      address myriad questions. What are the essential disorder-specific family
      processes that should be targeted by interventions? Hostility, criticism,
      communication, attachment and autonomy, attributional sets, and behavior
      management are important processes of family life, but each may have more
      relative importance for specific disorders. With a greater understanding of these
      processes, treatments could be tailored to target these mechanisms more
      efficiently and effectively. (ABSTRACT TRUNCATED)

PMID- 11449818
TI  - FMS*Calciumfluor increases alkaline phosphatase expression during osteogenesis in
      vitro of tibia-derived rat osteoblasts by activation of G alpha 0/G alpha i
      proteins.
AB  - We studied the involvement of G-proteins in transducing the inductive signal
      generated by treatment of tibial-derived neonatal rat osteoblasts (ROB) cultured
      in vitro with FMS*Calciumfluor, a homeopathic preparation utilized in the therapy
      of osteoporosis. We previously reported that FMS*Calciumfluor acts as inducer and
      potentiator of osteogenic differentiation in vitro, among other effects, by
      increasing the expression of Alkaline phosphatase (AP). We utilized Pertussis
      Toxin (PTX), an inhibitor of G alpha 0/G alpha i proteins, Mastoparan 7, an
      activator of G alpha 0/G alpha i proteins and Cholera Toxin (CTX), a stimulator
      of G alpha s protein to show involvement of specific G proteins in the inductive
      effect on AP of FMS*Calciumfluor. We here show that the increase in AP expression
      induced by FMS*Calciumfluor is dependent on the activation of G alpha 0/G alpha i
      proteins, while it is unaffected by the activation stage of the G alpha s
      protein. Moreover, we show that the expression of endogenous AP during
      osteogenesis in vitro is regulated independently from G proteins, and unaffected
      by their activation stage and therefore that treatment with FMS*Calciumfluor
      activates a new pathway of cellular response.

PMID- 11449819
TI  - Adhesion of bacteria and diatoms to the exoskeleton of the harpacticoid copepod
      Tigriopus fulvus in culture: electron and epifluorescent microscope study.
AB  - In the marine environment associations between picoplankton and copepods are very
      important not only for the lifestyle of these animals, but also for marine
      ecosystems and human health. In the present study we investigated the biofouling
      of Tigriopus fulvus in culture and possible effects of this colonization by means
      of scanning electron microscopy and epifluorescence microscopy. These
      investigations show that T. fulvus is heavily and not uniformly colonized by
      bacteria and algae.

PMID- 11449820
TI  - A specific alkaline phosphatase of amphibia integument levamisole effect on short
      circuit current (SCC).
AB  - Using the Ussing chamber technique we have measured the short-circuit current
      (SCC), and so the ion transport, in the ventral skin of samples of Rana esculenta
      complex. The animals were not exposed to experimental treatment, and on SCC we
      have observed the effect of levamisole, administered either on external or
      internal side. Levamisole 0.0025 mM was ineffective; higher concentrations (0.025
      mM, 2.5 mM), which inhibit alPase activity in tissue extracts and sections,
      induced an increase in SCC measurements and the effect was proportional to the
      concentration. Levamisole 25 mM produced a rapid and transitory increase of SCC,
      followed by a very quick decrement of it. Because of the action of Levamisole,
      "specific inhibitor of alPase activity", on ion transport in Rana skin, we
      propose that the alPase enzyme is probably involved in ion cutaneous transport
      and thus in the adaptative osmoregulation in the integument of amphibia.

PMID- 11449821
TI  - Cultures and thermal analysis of the marine microalga Tetraselmis suecica Kylin
      (Butch).
AB  - In this paper, the growth of the marine microalga Tetraselmis suecica was
      investigated using thermogravimetry (TG) and differential thermal analysis (DTA)
      to determine suitable diets for larval and juvenile development in aquaculture
      systems. Microalgae were maintained in synthetic sea water (19@1000 salinity, 18
      degrees C constant temperature) and the algal growth was evaluated by cell
      abundance. Exponential, stationary and senescence cells were analyzed by TG and
      DTA. The results of thermal analysis pointed out marked differences between
      exponential, stationary and senescence phases and showed that exponentially
      growing microalgae could represent a suitable food in aquaculture systems.

PMID- 11449822
TI  - Role of intracellular calcium ions in the physiopathology of fibromyalgia
      syndrome.
AB  - Calcium ions have a key role in the physiology of muscular contraction: changes
      in calcium ion concentration may be involved in the pathogenesis of fibromyalgia.
      Although, since the plasmatic level of calcium in fibromyalgia patients is always
      in the normal range, it seemed interesting to evaluate the intracellular calcium
      concentration. The study was carried out on two groups of subjects: 70 affected
      by fibromyalgia and 40 healthy controls. The results obtained show that in
      fibromyalgia patients the intracellular calcium concentration is significantly
      reduced in comparison to that of healthy controls: the reduced intracellular
      calcium concentration seems to be a peculiar characteristic of fibromyalgia
      patients and may be potentially responsible for muscular hypertonus. The
      effective role of this anomaly in the physiopathology of fibromyalgia and the
      potential role of drugs active on the calcium homeostasis are still to be
      confirmed.

PMID- 11449823
TI  - Pointing movement in short and long-term exposure to hypoxia.
AB  - Kinematics variables of pointing movements where assessed in five adult subjects
      exposed acutely (30 min) and chronically (10 days) to a low O2 mixture (13.5% O2
      in N2). Amplitude of displacement did not vary in both experimental conditions
      but movement duration markedly increased compared to pre and post exposure
      conditions. While in acute hypoxia the times of acceleration and deceleration are
      almost equal, in chronic hypoxia deceleration time exceeded of 100 ms the time of
      acceleration. The time from the peak acceleration to the peak of deceleration
      ("switch" time) increased in both experimental conditions and was about 50% of
      the movement duration. This time lengthening at hypoxia may be explained either
      by alteration of propioceptive loops or by a different strategy elaborated by the
      CNS to generally slow accurate movements.

PMID- 11449824
TI  - Application of the principal component analysis (PCA) to the ecological study of
      an artificial environment: the tunny-fishing net of Camogli (Ligurian Sea).
AB  - The management of the marine environment and resource exploitation depend on the
      knowledge of both water conditions and ecological relationships between
      organisms. In the framework of fishing problems, an adequate food availability is
      important in order to allow maintaining and growth of fish stocks. The tunny
      fishing of Camogli, owing to the coco-fibre texture of its net, can improve the
      trophic resources allowing the settlement of organisms eaten by fish. The
      distribution and composition of settled organisms was studied during the campaign
      1988 by microscopical methods. The results have been elaborated by using
      multivariate (PCA) methods. Foraminifers, ciliates, hydroids, nematodes and
      copepods were the mainly observed groups. Their variations with season and depth
      and the relationships with caught fish species are presented. The elaboration of
      data by PCA allowed an easy and complete interpretation of the obtained complex
      data set showing the existence of a "rope" and of a "depth" effect.

PMID- 11449825
TI  - Chromatin accessibility to DNA minor groove ligands in vitro: role of linker
      histones and amino-terminal domains of octamer histones.
AB  - Using the circular dichroism spectra, induced in the visible range by the binding
      of minor groove ligands to DNA, we found that two drugs, DAPI and Hoechst 33258,
      are able to occupy their specific sites even when these are located inside the
      nucleosome structure. This high accessibility of the binding sites in the
      nucleosome is not modified by the removal of the amino-terminal domains of the
      octamer histones and, surprisingly, it is not reduced by the presence of linker
      histone. Interesting and reasonable differences were found in the association
      constants, that reveal the "reluctance" of the ligands to bind the DNA-minor
      groove when the histones are present.

PMID- 11449826
TI  - [To die alone: a symptom of dehumanization?].

PMID- 11449827
TI  - [The significance of bovine spongiform encephalopathy epidemics for transfusion
      medicine].

PMID- 11449828
TI  - [Philosophy, ethics and methods. What is the connection?].

PMID- 11449829
TI  - [Placebo and superfluous actions in clinical practice].
AB  - There is a therapeutic potential in the doctor-patient relationship, in the
      diagnostic process, and in the symbolic elements of medical therapy. This
      unspecific effect seems, however, to be mainly caused by the doctor-patient
      relationship and the diagnostic process, and superfluous investigations and
      treatments should therefore not be initiated due to an unfounded idea about the
      potential of the so-called placebo effect. This article tries to identify the
      unspecific elements in therapy and their therapeutic potential. It is pointed
      out, that the outcome of a treatment is a sum of the effect of the relationship
      between the physician and the patient, plus the specific biological treatment
      effect, plus the incidental effect including the effect of the patients knowledge
      of being under treatment. The article asks for more research in the first and the
      last of these three components of therapy.

PMID- 11449830
TI  - [Ogilvie syndrome].
AB  - Ogilvie's syndrome is a rare condition with progressive dilatation of the
      proximal colon without mechanical obstruction. Untreated it can lead to coecal
      perforation, peritonitis and death. It develops in patients with medical or
      surgical complications, but can be idiopathic. Caesarean section is the most
      common preceding surgical procedure. An imbalance between the parasympathetic and
      the sympathetic innervation of the intestine is thought to be the cause. Trauma
      to the retroperitoneum, infections, bleeding and electrolyte disturbances,
      hormonal changes and medicamina are predisposing factors. The syndrome can result
      in perforation of the coecum as early as the third or fourth day. Therefore a
      diagnostic abdominal X-ray should not be delayed by the intermittent presence of
      flatus and stool which is characteristic for this pseudo-obstructive condition.
      Medical treatment with neostigmine may be successful, coloscopic decompression of
      the colon is effective as is placing a tube in or close to coecum. If laparotomy
      is necessary, coecostomy has lower mortality than ileo-coecal resection.

PMID- 11449831
TI  - [Ogilvie syndrome after Cesarean section].
AB  - INTRODUCTION: Ogilvie's syndrome, acute pseudo-obstruction of the colon, can lead
      to perforation of the caecum and death. The syndrome is not well known and
      diagnosis can be difficult to make in time. METHODS: We analysed seven cases of
      Ogilvie's syndrome with the aim of improving diagnostics. RESULTS: All had
      prolonged labour before cesarean section, which was complicated by bleeding. All
      were treated with syntocinon, a hormone that may influence gastrointestinal
      motility. All patients developed abdominal meteorism within a few days of
      operation, which increased despite the passing of flatus and stool. Five cases
      resulted in caecum perforation before the correct diagnosis and treatment were
      made. Perforation occurred on days 3-4, day 5, or probably days 8-10 after the
      operation. One of these patients, who suffered from severe adipositas, died.
      CONCLUSION: It is very important to make an early diagnosis, as the condition can
      progress quickly. Diagnosis should be made on the history, clinical assessment,
      and abdominal X-ray. Intermittent flatus and stool are characteristic of this
      truly non-obstructive condition and should not therefore delay a diagnostic X
      ray.

PMID- 11449832
TI  - [To die alone, a big city problem?].
AB  - The question whether being found dead is a problem related to living in a big
      city was examined by using death certificates from a 3-month period in 1994. The
      rates of persons found dead were higher for both sexes in the City of Copenhagen
      than in the rural County of Storstrom. The age distribution showed that the rate
      increased with advancing age. The vast majority were found dead in their own
      home, although the rate was higher in Copenhagen than in Storstrom. Whereas the
      manner of death was natural for the majority of cases in both areas, more deaths
      with an uncertain manner of death were recorded in Copenhagen than in Storstrom
      (32% vs 9%). In general, suicide or accident was more often reported in those
      found dead in the County of Storstrom than in those in Copenhagen. The cause of
      death was unknown in 46% of deaths in Copenhagen where 16% had died from external
      causes, proportions that were 58% and 21%, respectively, in Storstrom. The rate
      of legal autopsies was higher in subjects with an uncertain manner of death than
      in the rest, and was also associated with an age below 40 years. We conclude that
      being found dead is related to living in a big city, although the reason(s) for
      this remains unidentified.

PMID- 11449833
TI  - [Sociodemographic predictors of therapeutic results in patients with chronic, non
      malignant pain].
AB  - INTRODUCTION: Chronic pain is in its nature multidimensional and is most
      successfully treated by a multidisciplinary approach. Some patients do not
      benefit from treatment, and psychological and socio-economic factors may play a
      major role. The present study investigated the ability of sociodemographic
      variables to predict the short-term effect of multidisciplinary treatment in
      patients with chronic pain who where referred consecutively to a Danish
      multidisciplinary pain centre. METHOD: Pain scores (VAS) and health-related
      quality of life (HRQL) were assessed. On entry and three and six months later
      HRQL was evaluated by medical outcome short form (SF-36) and the psychological
      general well-being scale (PGWB). Sociodemographic variables were: age, gender,
      educational level, civil status employment status, and disability pension (DP)
      status. RESULTS: Of the sociodemographic variables evaluated, only the DP status
      seemed to be a significant outcome predictor. Patients applying for a DP do not
      improve. Patients receiving a DP and those who do not achieved moderate
      improvements, but these were significantly larger. The same pattern was seen for
      changes in psychological well-being and social functioning. The DP status
      predicted improvement in pain and social functioning. DISCUSSION: The present
      study indicates that the multidimensional problems experienced by patients
      applying for a DP are dominated by sociodemographic factors. Focus on the
      solution of these socio-economic problems is important, if patients with chronic
      pain are to benefit from multidisciplinary pain treatment.

PMID- 11449834
TI  - [Therapeutic results in chronic, non-malignant pain in patients treated at a
      Danish multidisciplinary pain center compared with general practice. A randomized
      controlled clinical trial].
AB  - INTRODUCTION: Multidisciplinary pain treatment (MPT) is generally considered to
      be the most effective treatment of chronic pain, but its long-term effect has not
      yet been firmly established. METHODS: This randomised controlled study compared
      the effect of outpatient MPT with that of treatment by general practitioners
      after initial supervision by a pain specialist (GP group) and with a six-month
      waiting list group (WL group). The participants were 189 patients with chronic
      non-malignant pain. On referral and at three and six months, the patients filled
      in questionnaires evaluating pain intensity, health-related quality of life
      (HRQL), and the use of analgesics. RESULTS: At six months, the patients allocated
      to MPT (N = 63) reported a reduction in pain intensity (p < 0.001), and an
      improvement in psychological well-being (p < 0.001), quality of sleep (p < 0.05),
      and physical functioning (p < 0.05). The WL group (N = 63) had a statistically
      significant deterioration in most of the HRQL measures. The only effect of
      treatment found in the GP group was a reduction in the use of short-acting
      opioids. In the MPT group, the use of opioids administered on demand and short
      acting opioids was decreased (p < 0.001). No change in the use of analgesics was
      seen in the WL group. DISCUSSION: The study showed that (i) in the MPT group
      there was a significant reduction in pain intensity and an improvement in HRQL
      compared to the WL group, and (ii) the mere establishment of a pain diagnosis and
      management plan by a specialist was not sufficient to enable the referring GP to
      manage patients with severe chronic pain.

PMID- 11449835
TI  - [Gastrointestinal decontamination. Use in non-drug poisoning].
AB  - AIM: To assess whether Danish doctors use gastrointestinal decontamination (GID)
      in non-drug poisoning in accordance with recommendations for restricted
      application. METHOD: Doctors telephoning the Danish Poisons Information Centre
      about non-drug exposures were surveyed prospectively. The doctor's intention to
      treat, the age and sex of the patient, and information about poison, amount and
      time since exposure, were assessed. RESULTS: Of the 138 telephone calls, 64%
      concerned children below 5 years of age and 24% patients above 15 years of age.
      The risk was estimated as insignificant in 63%, minor in 30%, significant in 6%
      and severe in only 1%. The insignificant risk was found mainly in children and
      the severe risk solely in those above 15 years of age. GID was proposed in 33%
      with the highest frequency in children with minor or insignificant risks, and the
      time since exposure did not influence the frequency of GID. Charcoal was not
      proposed. CONCLUSION: It is clear from this small sample that Danish doctors tend
      to use GID more often than is recommended. Activated charcoal was apparently not
      used. GID was in most cases used in children with insignificant and minor risks,
      where it is likely to do more harm than good.

PMID- 11449836
TI  - [Intraspinal tumor--a rare cause of low back pain in school children].
AB  - On the background of two cases, characteristic features of intraspinal tumours in
      school children are discussed with the purpose of early detection of this and
      other serious back diseases in the large group of school children with non
      specific low back pain. Special attention should be paid to children with
      recurrent or persistent low back pain. MRI scanning is preferable to CT, when a
      spinal tumour is suspected.

PMID- 11449837
TI  - [Minimal residual disease in hematology].

PMID- 11449838
TI  - [Role of molecular genetic investigations in the diagnosis of acute leukemias and
      in the detection of minimal residual disease].
AB  - Chimera gene products, the molecular hallmark of acute leukemias were detected
      and quantified for diagnostic purposes and for follow up of therapy and
      characterization of minimal residual disease. In acute lymphoid leukemia mainly
      the bcr-abl, and in acute myeloid leukemias, depending on the morphological
      classification, the aml-eto, bcr-abl, pml-rara, plzf-rara, and cbfb-myh chimeras
      were investigated. The determinations were based on reverse transcriptase
      polymerase chain reaction. The results were used in diagnosis of 315 new leukemic
      patients, and in follow up of 70 ones. In the present paper the usefulness of the
      applied methods is illustrated by presentation of data of 38 (27, acute myeloid
      leukemias and 11 acute lymphoid ones) patients out of the 139 treated in the
      National Institute during the last years.

PMID- 11449839
TI  - [Quality indicators of hospital care: evaluation of patient care in acute
      myocardial infarction].
AB  - In the international hospital accreditation programs there is an increasing
      emphasis on involving performance indicators. The inpatient mortality rate of AMI
      patients and the usage of thrombolytic therapy are very common, evidence based
      indicators of these programs. The authors goal was to analyze the applicability
      of these indicators in the evaluation of the Hungarian hospital care. In Hungary,
      there is a data collection system on every inpatient case. This database was used
      to determine the above mentioned two indicators for 1997 and 1998. They
      calculated by hospital group level, by institutions and by geographic areas crude
      rates and rates adjusted for age and gender, and for severity using the different
      DRGs of AMI patients. In these two years the inpatient mortality rates of AMI
      patients were 20.4% and 21.7%, and the usage of thrombolytic therapy were 9.9%
      and 11.8%, respectively. Using indirect standardization methodology in the usage
      of thrombolytic therapy, they found high differences among the counties compared
      to the national average, the range was 51-199%, and among the institutions 0
      306%, respectively. It is clear, that there are huge differences in the curative
      processes and in the inpatient mortality rates of AMI patients among the
      hospitals. The differences are developed by chance, there are no close
      connections either to hospital groups, or to geographical locations. Because of
      the difficulties of risk adjustment, they suggested that indicators were suitable
      for benchmarking. It is necessary to implement in the national quality criteria
      system different indicators for evaluating the patient care, to develop programs
      for auditing the best and worst hospitals and to introduce standards for assuring
      the validity of the basic data.

PMID- 11449840
TI  - [Methods for in vivo investigation of human microcirculation].
AB  - Microcirculatory disorders play a major role in the development of organ failure
      in a variety of conditions. Perfusion changes may be visualized by static and
      dynamic methods, with direct and indirect techniques. Orthogonal polarization
      spectral imaging is a novel method of imaging the human microcirculation. The
      technique employs reflected light without fluorescent dyes and allows clinical
      assessment of the dynamic of the microvascular network of internal solid organs.
      Principles of the technique and indications of use are briefly discussed.

PMID- 11449841
TI  - [Problems of differential diagnosis in synovial sarcoma].
AB  - The authors present a woman's case (age 50), who was hospitalised several times
      as she often had pain in her left leg and knee for one year. The pain increased
      in the last 2 months. The final diagnosis, the primer synovial sarcoma of the
      left knee was justified only post mortem. Not only this alteration in the knee
      caused the pain in the left leg. The symptoms of sciatic pain caused by lumbal
      discus herniation also occurred which made the diagnosis more difficult.
      Referring to relevant data in literature the authors analyse the differential
      diagnostic aspects of the final diagnosis and the clinical spectrum of the
      illness.

PMID- 11449842
TI  - [Moratorium proposal for xenotransplantation].

PMID- 11449843
TI  - [Let's use correct Latin!].

PMID- 11449844
TI  - Itraconazole, terbinafine possibly linked to liver failure.

PMID- 11449845
TI  - CDC expands influenza vaccination window, acknowledges supply problems.

PMID- 11449846
TI  - Survey finds providers in agreement on need for better health care.

PMID- 11449847
TI  - Oregon Death with Dignity Act may improve end-of-life care.

PMID- 11449848
TI  - Two new ophthalmic solutions enter glaucoma market.

PMID- 11449849
TI  - Test of USP program for testing dietary supplements gets under way.

PMID- 11449850
TI  - Increase in drug expenditures tied to more prescriptions, costlier brand-name
      products.

PMID- 11449851
TI  - Settlement plan approved for lorazepam, clorazepate overcharges.

PMID- 11449852
TI  - Still the handmaiden.

PMID- 11449853
TI  - Probiotics: "living drugs".
AB  - The uses, mechanisms of action, and safety of probiotics are discussed.
      Probiotics are live microorganisms or microbial mixtures administered to improve
      the patient's microbial balance, particularly the environment of the
      gastrointestinal tract and the vagina. The yeast Saccharomyces boulardii and the
      bacterium Lactobacillus rhamnosus, strain GG, have shown efficacy in clinical
      trials for the prevention of antimicrobial-associated diarrhea. Other probiotics
      that have demonstrated at least some promise as prophylaxis for this type of
      diarrhea are Lactobacillus acidophilus, Bifidobacterium longum, and Enterococcus
      faecium. The use of S. boulardii as an adjunctive treatment to therapy with
      metronidazole or vancomycin has been found in controlled studies to decrease
      further recurrences of Clostridium difficile-associated disease. Other
      gastrointestinal disorders for which probiotics have been studied include
      traveler's diarrhea, acute infantile diarrhea, and acute diarrhea in adults.
      Several Lactobacillus species given in yogurt or in tablet or suppository form
      have shown clinical efficacy as a treatment for vaginal infections. Lactobacillus
      strains have also been examined as a treatment for urinary-tract infections.
      Putative mechanisms of action of probiotics include production of pathogen
      inhibitory substances, inhibition of pathogen attachment, inhibition of the
      action of microbial toxins, stimulation of immunoglobulin A, and trophic effects
      on intestinal mucosa. The available probiotics are considered nonpathogenic, but
      even benign microorganisms can be infective when a patient is severely
      debilitated or immunosuppressed. Probiotics have demonstrated an ability to
      prevent and treat some infections. Effective use of probiotics could decrease
      patients' exposure to antimicrobials. Additional controlled studies are needed to
      clearly define the safety and efficacy of these agents.

PMID- 11449854
TI  - Determinants of satisfaction with prescription drug plans.
AB  - Satisfaction among health plan members with their prescription drug coverage was
      studied. Interviews of patrons of 10 randomly selected community pharmacies in
      the Pittsburgh area were conducted by entry-level Pharm.D. students during spring
      1999. Survey participants were asked to indicate their level of satisfaction with
      each of nine items dealing with various components of pharmacy benefit plans and
      to provide health-related and sociodemographic information. Differences in
      responses were assessed with univariate and multivariate statistics. A total of
      504 people were interviewed. The results of general linear model and multivariate
      procedures indicated that the sociodemographic characteristics of respondents did
      little to explain variations in satisfaction. Differences were governed primarily
      by having a choice of plans in which to enroll and of perceptions of plan
      limitations. Most respondents were overwhelmingly satisfied with the quality of
      their prescription drug plans. Government-sponsored plans were rated at least as
      well as private plans. Members of health care plans in a metropolitan region were
      satisfied with their prescription drug coverage. Satisfaction was primarily
      determined by perceptions about coverage limitations and having a choice of
      plans.

PMID- 11449855
TI  - Policies on documentation and disciplinary action in hospital pharmacies after a
      medication error.
AB  - Hospital pharmacies were surveyed about policies on medication error
      documentation and actions taken against pharmacists involved in an error. The
      survey was mailed to 500 randomly selected hospital pharmacy directors in the
      United States. Data were collected on the existence of medication error reporting
      policies, what types of errors were documented and how, and hospital
      demographics. The response rate was 28%. Virtually all of the hospitals had
      policies and procedures for medication error reporting. Most commonly,
      documentation of oral and written reprimand was placed in the personnel file of a
      pharmacist involved in an error. One sixth of respondents had no policy on
      documentation or disciplinary action in the event of an error. Approximately one
      fourth of respondents reported that suspension or termination had been used as a
      form of disciplinary action; legal action was rarely used. Many respondents said
      errors that caused harm (42%) or death (40%) to the patient were documented in
      the personnel file, but 34% of hospitals did not document errors in the personnel
      file regardless of error type. Nearly three fourths of respondents differentiated
      between errors caught and not caught before a medication leaves the pharmacy and
      between errors caught and not caught before administration to the patient. More
      emphasis is needed on documentation of medication errors in hospital pharmacies.

PMID- 11449856
TI  - Practical approach to determining costs and frequency of adverse drug events in a
      health care network.
AB  - The frequency, preventability, severity, root causes, and projected costs of
      adverse drug events (ADEs) occurring after or causing admission to a four
      hospital integrated academic health network were studied. The sample included all
      admissions during a 53-day study period. Events were identified through daily
      record review of a random patient sample, computerized flags, and self-reporting.
      A case review committee validated the occurrence, classification, and root causes
      of the events. Additional length of stay and costs associated with ADEs were
      analyzed by using a case-control, multiple linear regression model. The estimated
      ADE rate during hospitalization was 4.2 events per 100 admissions, with a cost of
      $2162 per ADE. In addition, 3.2% of admissions were caused by ADEs, with an
      associated cost of $6685 per event. Fifteen percent of hospital ADEs and 76% of
      ADEs causing admission were judged preventable. The annual cost to the
      organization for events occurring during hospitalization was $1.7 million, and
      the cost of preventable ADEs was $260,000, while the projected costs of
      preventable ADEs causing admission were $3.8 million. The rate of admissions to
      the mental health center caused by ADEs was higher than for other settings at
      13.6%, with a cost of preventable ADEs of $1.3 million. Patient noncompliance was
      judged to be the cause of the 69% of the ADEs causing admission. Seventy-one
      percent of the serious medication errors occurred at the prescribing stage of the
      medication-use process. ADEs were frequent, costly, and often preventable and
      resulted in many admissions to a mental health center.

PMID- 11449857
TI  - Economic burden of influenza-like illness in long-term-care facilities.
AB  - Direct medical costs and medically related transportation costs incurred by
      patients in long-term-care facilities (LTCFs) as a result of influenza-like
      illness (ILI) were studied. The study was conducted from the payer's perspective.
      Charts were reviewed retrospectively for all patients who were residents of four
      Richmond, Virginia, LTCFs between January 1 and May 31, 1999. Consultant
      pharmacists gathered data on patient demographics, ILI status, vaccination for
      influenza and streptococcal pneumonia, diagnosis of asthma or chronic obstructive
      pulmonary disease, and utilization of health care services related to ILI.
      Services included the use of antimicrobials, antivirals, and respiratory drugs;
      emergency room visits; diagnostic tests; hospitalizations; and medically related
      transportation. Costs were based on average wholesale prices (for drugs) and
      Medicare or Medicaid reimbursement rates. Data were collected for 551 patients.
      Of these, 112 patients had been diagnosed with 128 cases of ILI during the study
      period. Twenty-two patients with ILI had 28 visits to emergency rooms, and 30
      patients with ILI had 36 hospitalizations. The mean +/- S.D. cost per case of ILI
      was $1341 +/- $2063; inpatient hospital costs accounted for 84% of this amount.
      Centers for Disease Control and Prevention criteria for ILI provided a lower
      incidence of ILI and, consequently, a lower mean +/- S.D. cost of $968 +/- $1806
      per case. ILI in patients in four LTCFs in Richmond, Virginia, generated
      substantial costs, the bulk of which resulted from hospitalization. A substantial
      percentage of the patients apparently were not immunized.

PMID- 11449858
TI  - Stability of methylprednisolone sodium succinate in pediatric parenteral
      nutrition mixtures.

PMID- 11449859
TI  - Prescribing privileges among pharmacists in Veterans affairs medical centers.

PMID- 11449860
TI  - Implementing a program for switching from i.v. to oral antimicrobial therapy.
AB  - Management Case Studies describe approaches to real-life management problems in
      health systems. Each installment is a brief description of a problem and how it
      was dealt with. The cases are intended to help readers deal with similar
      experiences in their own work sites. Problem solving, not hypothesis testing, is
      emphasized. Successful resolution of the management issue is not a criterion for
      publication--important lessons can be learned from failures, too.

PMID- 11449861
TI  - Husbands' and wives' reports of contraceptive use.
AB  - Many Demographic and Health Surveys (DHS) in the past decade have queried
      husbands and wives about their current contraceptive use. In this study, couples'
      concurrence on use and method used is compared by means of data from 23
      countries, mostly in sub-Saharan Africa. Husbands report higher levels of use
      than do their wives in every country studied, with ranges from 2 percent higher
      (Brazil) to 150 percent higher (Mali). Many of the discrepancies are the result
      of husbands' sole reports of periodic abstinence and condom use. Couples with
      polygynous husbands show less concurrence than do monogamous couples, although
      the majority of these differences could result from a data-collection problem.
      Monogamous couples in which one or both spouses reported having extramarital sex
      partners show less concurrence than do monogamous couples reporting no other
      partners. Problems of validity of both husbands' and wives' reports are
      discerned, and in the few instances where a direct comparison is possible, wives'
      reports are shown to have greater validity. Logistic regression results show that
      spousal discussion about family planning and greater female education are
      consistent predictors of concurrence.

PMID- 11449862
TI  - Bargaining power within couples and use of prenatal and delivery care in
      Indonesia.
AB  - Indonesian women's power relative to that of their husbands is examined to
      determine how it affects use of prenatal and delivery care. Holding household
      resources constant, a woman's control over economic resources affects the
      couple's decision-making. Compared with a woman with no assets that she perceives
      as being her own, a woman with some share of household assets influences
      reproductive health decisions. Evidence suggests that her influence on service
      use also varies if a woman is better educated than her husband, comes from a
      background of higher social status than her husband's, or if her father is better
      educated than her father-in-law. Therefore, both economic and social dimensions
      of the distribution of power between spouses influence use of services, and
      conceptualizing power as multidimensional is useful for understanding couples'
      behavior.

PMID- 11449863
TI  - Adolescent pregnancy and parenthood in South Africa.
AB  - South Africa's total fertility rate is estimated to be one of the lowest in sub
      Saharan Africa, fewer than three births per woman nationally and declining. At
      the same time, adolescent childbearing levels remain high: More than 30 percent
      of 19-year-old girls are reported to have given birth at least once. Evidence
      from focus-group discussions conducted in urban and rural areas in South Africa
      with young black women and men, and with the parents of teenage mothers, is used
      to consider the experience of early parenthood, including the role of paternity,
      education, work opportunities, and subsequent fertility. In South Africa, in
      contrast to many other settings, teenage mothers may return to school once they
      have given birth, and this opportunity is strongly related to a long delay before
      the birth of a second child. Educated girls also tend to bring more bridewealth,
      which may encourage parents to support their daughters' schooling, and perhaps
      their return to school following childbirth. The support of the child, however,
      is often subject to paternal recognition and commitment, even though boys are
      unwilling to admit paternity because it jeopardizes their educational and
      employment opportunities.

PMID- 11449864
TI  - Husband-wife survey responses in Malawi.
AB  - Previous efforts by demographers to describe and explain spousal differences in
      reporting about family planning behavior have focused on individual attributes
      that are assumed to be related to the practice of contraception. This study
      extends that research by documenting spousal disagreement on a range of issues-
      household items, livestock, children, and spousal communication about fertility,
      family planning, and AIDS. Using data from a 1998 study of 585 monogamous couples
      in rural Malawi, the analysis identifies a systematic gender component to
      reporting: For many of the survey questions considered, when spouses disagree,
      husbands are more likely to say "yes" and wives "no." The findings are
      interpreted in terms of gendered strategies in the interview process.

PMID- 11449865
TI  - Lebanon 1996: results from the Lebanon Maternal and Child Health Survey.

PMID- 11449866
TI  - Madagascar 1997: results from the Demographic and Health Survey.

PMID- 11449867
TI  - Obstacles to contraceptive use in Pakistan: a study in Punjab.
AB  - The principal aim of this study is to assess the strength in Pakistan of a set of
      hypothesized obstacles to practicing contraception. Survey data are analyzed that
      were collected in Punjab province in 1996 and that contain unusually detailed
      measurement of various perceived costs of practicing contraception, as well as
      focused measurement of fertility motivation. The framework guiding the research
      specifies six major obstacles to contraceptive use: the strength of motivation to
      avoid pregnancy, awareness and knowledge of contraception, the social and
      cultural acceptability of contraception, perceptions of the husband's preferences
      and attitudes, health concerns, and perceived access to services. Net effects of
      each obstacle are estimated through structural equation modeling of the intention
      to practice contraception in the near future, in which the six obstacles are
      treated as latent variables. The estimates indicate that the two principal
      obstacles to using a contraceptive are the woman's perception that such behavior
      would conflict with her husband's fertility preferences and his attitudes toward
      family planning and her perception of the social or cultural unacceptability of
      contraception. The results confirm the value of taking contraceptive costs
      seriously, and, in particular, of attempting to measure these costs in empirical
      research on family planning.

PMID- 11449869
TI  - CDC advises delaying tetanus booster shots for adults, adolescents until 2002.

PMID- 11449868
TI  - Senator introduces legislation to recognize pharmacists as health care providers.

PMID- 11449870
TI  - CPOE reduces number of steps in medication-use process.

PMID- 11449871
TI  - Monoclonal antibody licensed for third-line treatment of B-cell chronic
      lymphocytic leukemia.

PMID- 11449872
TI  - Federal reports say oxycodone abuse is on the rise.

PMID- 11449873
TI  - Researchers urge caution with standard regimen for metastatic colorectal cancer.

PMID- 11449874
TI  - Ninety-day versus thirty-day drug-dispensing systems.

PMID- 11449875
TI  - Applying research ethics to quality-related initiatives.

PMID- 11449876
TI  - Levetiracetam.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and
      dosage and administration of levetiracetam are reviewed. Levetiracetam is an
      adjunctive treatment for partial-onset epileptic seizures. This drug inhibits
      seizure activity via a mechanism that does not involve excitatory or inhibitory
      neuronal pathways. Oral bioavailability is about 100%, and food does not alter
      absorption. Levetiracetam is minimally plasma protein bound (10%). Peak time to
      absorption after oral administration is one hour, and steady state is achieved in
      two days with twice-daily administration. Three clinical studies have
      demonstrated levetiracetam's ability to reduce seizure frequency in patients with
      partial-onset epilepsy. The most commonly reported adverse effects in clinical
      trials were somnolence, dizziness, infection, and asthenia. The potential for
      interactions with medications that are hepatically metabolized is minimal. The
      starting dosage is 500 mg twice a day; the maximum dosage is 3000 mg/day within
      four weeks. Levetiracetam is effective as an adjunctive treatment of partial
      onset epilepsy with or without secondary generalization.

PMID- 11449877
TI  - Nateglinide.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects,
      interactions, and dosage of nateglinide are reviewed. Nateglinide is an oral
      hypoglycemic agent approved for use alone or in combination with metformin as an
      adjunct to diet and exercise for the treatment of type 2 diabetes mellitus.
      Nateglinide, an amino acid derivative of D-phenylalanine, stimulates the
      secretion of insulin by binding to the ATP potassium channels in pancreatic beta
      cells. The result is an increase in beta-cell calcium influx, which leads to
      rapid, short-lived insulin release. The drug is rapidly and completely absorbed
      in the small intestine. The estimated bioavailability is 72%. Nateglinide is
      highly bound to plasma proteins, is metabolized extensively by the liver, and has
      an elimination half-life of 1.4 hours. Several clinical trials of nateglinide,
      alone and in combination with other oral hypoglycemic agents, have found the drug
      to be safe, effective, and well tolerated. The most common adverse effects are
      nausea, diarrhea, dizziness, and lightheadedness. There is a potential for
      interactions between nateglinide and medications affected by the cytochrome P-450
      isoenzyme system. Dosage regimens ranging from 60 to 240 mg have been evaluated.
      The maximum effective dosage is 120 mg taken 10 minutes before meals three times
      a day. Nateglinide is an alternative to second-generation sulfonylureas for the
      treatment of type 2 diabetes mellitus. Additional comparative trials are needed
      to fully elucidate nateglinide's role.

PMID- 11449878
TI  - Caspofungin acetate: an antifungal agent.
AB  - The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, and
      adverse effects of caspofungin acetate are reviewed. Caspofungin acetate is an
      echinocandin with fungicidal activity against a wide range of pathogens,
      including Candida spp., Aspergillus spp., and Histoplasma spp. It is active
      against fluconazole-resistant and fluconazole-susceptible strains of Candida
      albicans. Caspofungin acetate irreversibly inhibits the enzyme 1,3-beta-D-glucan
      synthase, preventing the formation of glucan polymers and disrupting the
      integrity of the fungal cell wall. Caspofungin acetate has an elimination half
      life of 9-10 hours and is suitable for once-daily regimens. Data from animal and
      human studies demonstrate that the drug is 80-96% protein bound. Less than 3% of
      the dose is eliminated unchanged in the urine, and the proposed route of
      elimination is hepatic. In a trial of 128 patients with Candida esophagitis,
      clinical response rates were higher with caspofungin acetate 50 or 70 mg/day
      (85%) than with amphotericin B 0.5 mg/kg/day (67%). Most enrolled patients had
      HIV infection, and almost half had CD4+ lymphocyte counts of less than 50
      cells/microL in another study, 56 immunocompromised patients with aspergillosis
      were treated with one 70-mg dose of caspofungin acetate, then 50 mg once a day.
      All patients had refractory invasive aspergillosis or were intolerant of
      amphotericin B, liposomal amphotericin B, or azole therapy. In patients who
      received at least one dose of caspofungin acetate, a favorable response was
      reported in 41%. In 128 patients who received either caspofungin acetate or
      amphotericin B, fewer caspofungin acetate recipients (1.4%) had elevated serum
      creatinine levels and discontinued therapy because of adverse effects (4%) than
      amphotericin B recipients (15% and 22%, respectively). The manufacturer's
      recommended dose for infections caused by Candida or Aspergillus spp. has not
      been determined. Caspofungin acetate appears to be fungicidal, with a wide
      spectrum of antifungal activity and a good safety profile. The lack of adequate
      efficacy and safety data in humans makes a recommendation to add this drug to the
      formulary premature. Pending advanced clinical trials and cost information,
      caspofungin acetate may be a reasonable addition to the formulary, particularly
      in hospitals with large immunocompromised patient populations.

PMID- 11449879
TI  - Stability and compatibility of tirofiban hydrochloride during simulated Y-site
      administration with other drugs.
AB  - The stability and compatibility of tirofiban hydrochloride injection during
      simulated Y-site administration with various other drugs were studied. Tirofiban
      hydrochloride, dobutamine, epinephrine hydrochloride, furosemide, midazolam
      hydrochloride, and propranolol hydrochloride injections were each prepared from
      their respective concentrates in both 0.9% sodium chloride injection and 5%
      dextrose injection at both the minimum and maximum concentrations normally
      administered. The high-concentration solutions of midazolam hydrochloride and
      furosemide were used as is. Morphine sulfate was diluted in 5% dextrose injection
      only. Nitroglycerin premixed infusions, atropine sulfate injection, and diazepam
      injection were used as is. Tirofiban hydrochloride solutions were combined 1:1
      with each of the secondary drug solutions in separate glass containers. Samples
      were stored for four hours at room temperature under ambient fluorescent light
      and were assayed for drug content and degradation by high-performance liquid
      chromatography and for pH, appearance, and turbidity. All mixtures except those
      containing diazepam remained clear and colorless, with no visual or turbidimetric
      indication of physical instability. Mixing of tirofiban hydrochloride and
      diazepam solutions resulted in immediate precipitation. all remaining mixtures
      remained clear. There was no significant loss of any of the drugs tested, no
      increase in known degradation products, and no appearance of unknown drug-related
      peaks. The pH of all test solutions remained constant. Tirofiban hydrochloride
      injection 0.05 mg/mL was stable for at least four hours when combined 1:1 in
      glass containers with atropine sulfate, dobutamine, epinephrine hydrochloride,
      furosemide, midazolam hydrochloride, morphine sulfate, nitroglycerin, and
      propranolol hydrochloride at the concentrations studied. Tirofiban hydrochloride
      was incompatible with diazepam.

PMID- 11449880
TI  - National supply-chain survey of drug manufacturer back orders.
AB  - The impact of manufacturer back orders on the supply chain for pharmaceuticals in
      the institutional setting was studied. A questionnaire was distributed during May
      and June 2000 to 600 institutional pharmacies affiliated with a major national
      drug and supply group purchasing organization. The instrument included questions
      on basic institutional demographics, perceptions about the frequency of
      manufacturer back orders for pharmaceuticals, the quality of communication with
      manufacturers and wholesalers about back orders, the two most significant back
      orders that had occurred in the 12 months preceding the survey, and the reasons
      for and impact of back orders. A total of 170 usable surveys were returned (net
      response rate, 28.3%). Reported manufacturer back orders included an array of
      drug classes, including blood products, antimicrobials, antiarrhythmics,
      benzodiazepine antagonists, thrombolytics, corticosteroids, and
      antihypertensives. Respondents perceived significant back orders as increasing in
      frequency. Communication by manufacturers and wholesalers about back orders was
      reported to be relatively poor. A raw-material shortage was the most common
      reason given by manufacturers for back orders (36.5%), followed by a regulatory
      issue (23.2%). In most cases (92%), medical staff members had to be contacted,
      indicating an interruption in the normal drug distribution process. In over a
      third of instances, respondents stated that the back order resulted in less
      optimal therapy. A survey found that manufacturer back orders for pharmaceuticals
      were increasing in frequency and that information flow within the supply chain
      was insufficient to meet the needs of end users.

PMID- 11449881
TI  - Using a personal digital assistant to document clinical pharmacy services in an
      intensive care unit.
AB  - Management Case Studies describe approaches to real-life management problems in
      health systems. Each installment is a brief description of a problem and how it
      was dealt with. The cases are intended to help readers deal with similar
      experiences in their own work sites. Problem solving, not hypothesis testing, is
      emphasized. Successful resolution of the management issue is not a criterion for
      publication--important lessons can be learned from failures, too.

PMID- 11449882
TI  - Managing in a crisis: planning, acting, and learning.

PMID- 11449883
TI  - What I learned when I thought I was teaching.

PMID- 11449884
TI  - Transitions of muscle fiber phenotypic profiles.
AB  - Skeletal muscle is a complex, versatile tissue composed of a large variety of
      functionally diverse fiber types. The overall properties of a muscle largely
      result from a combination of the individual properties of its different fiber
      types and their proportions. Skeletal muscle fiber types, which can be delineated
      according to various parameters, for example, myofibrillar protein isoforms,
      metabolic enzyme profiles, and structural and contractile properties, are not
      fixed units but are capable of responding to altered functional demands and a
      variety of signals by changing their phenotypic profiles. This brief review
      summarizes our current understanding of the delineation of fiber types,
      modulations of their phenotypic profiles as induced under various conditions, and
      potential mechanisms involved in these transitions.

PMID- 11449885
TI  - Immunohistochemical localization of heparan sulfate proteoglycan in human
      gastrointestinal tract.
AB  - Heparan sulfate proteoglycans (HS-PGs) are associated with important cell
      functions, for example, cell motility, cell adhesion, and oncogenesis. We
      examined the localization of HS-PGs in normal and carcinoma tissues of the
      gastrointestinal tract to help elucidate their roles in these organs. Fresh
      surgical materials from 134 patients with carcinoma of the stomach or large
      intestine and 26 patients with various diseases of the small intestine were
      immunostained after fixation with 10E4 (an antibody against the HS of HS-PG) as a
      primary antibody. Immunoelectron microscopy (immunogold method) was also
      performed. The basolateral surfaces of normal tissues of the large and small
      intestines were strongly stained with antibody confirmed by electron microscopy.
      In the stomach, lesions with intestinal metaplasia showed the same staining as
      the intestines, although normal gastric tissue showed staining only in some parts
      of the basal layer of fundic and pyloric glands. Carcinoma tissues in all cases
      examined showed staining with antibody. Better results were obtained after
      fixation in acetic alcohol or zinc-containing solutions than in ordinary
      formalin. These characteristic localizations of HS-PG in intestines and stomachs
      suggest that this kind of HS-PG staining could be a hallmark characteristic of
      the intestine.

PMID- 11449886
TI  - Immunolocalization of NuMA and phosphorylated proteins during the cell cycle in
      human breast and prostate cancer cells as analyzed by immunofluorescence and
      postembedding immunoelectron microscopy.
AB  - The formation of mitotic centrosomes is a complex process in which a number of
      cellular proteins translocate to mitotic poles and play a critical role in the
      organization of the mitotic apparatus. The 238-kDa nuclear mitotic apparatus
      protein NuMA is one of the important proteins that plays a significant role in
      this process. NuMA resides in the nucleus during interphase and becomes
      transiently associated with mitotic centrosomes after multiple steps of
      phosphorylations. The role of NuMA in the interphase nucleus is not well known
      but it is clear that NuMA responds to external signals (such as hormones) that
      induce cell division, or heat shock that induces apoptosis. In order to determine
      the function of NuMA it is important to study its localization. Here we report on
      nuclear organization of NuMA during the cell cycle in estrogen responsive MCF-7
      breast cancer cells and in androgen responsive LNCaP prostate cancer cells using
      immunoelectron microscopy, and on correlation to MPM-2 monoclonal phosphoprotein
      antibody. These results show that NuMA is present in speckled and punctate form
      associated with distinct material corresponding to a speckled or punctate
      immunofluorescence appearance in the nucleus while MPM-2 is uniformly dispersed
      in the nucleus. At prophase NuMA disperses in the cytoplasm and associates with
      microtubules while MPM-2 is uniformly distributed in the cytoplasm. During
      metaphase or anaphase anti-NuMA labeling is associated with spindle fibers.
      During telophase NuMA relocates to electron-dense areas around chromatin and
      finally to the reconstituted nuclei. These results demonstrate NuMA organization
      in MCF-7 and LNCaP cells in the log phase of cell culture growth.

PMID- 11449887
TI  - Distribution of estramustine-binding protein during postnatal development of rat
      brain.
AB  - Estramustine-binding protein (EMBP) is expressed in several types of brain
      tumors, such as astrocytoma, ependymoma, and meningioma. It binds the cytotoxic
      drug estramustine with high affinity and is suggested to cause accumulation of
      the drug in EMBP-expressing tumor cells. In this study, the spatial distribution
      of EMBP in normal rat brain was studied with immunohistochemistry. Brains from
      male and female rats of different ages were used. EMBP was found in the cytoplasm
      of ependymal cells, in the leptomeninges, mainly the arachnoid, and in scattered
      neurons. Moreover, staining was seen in nuclei of choroid plexus cells, in the
      granular cell layer in the cerebellum, and in a few scattered endothelial cells.
      The nuclear staining was more frequent in younger animals. No obvious difference
      in EMBP expression between male and female rats was observed. The expression of
      EMBP in rat brain was confirmed with nested RT-PCR. Future studies are justified
      to elucidate the role of EMBP-like proteins in CNS and in brain tumors.

PMID- 11449888
TI  - Cytoskeletal and nuclear alterations in human lung tumor cells: a confocal
      microscope study.
AB  - Tumor cells generally present various types of nuclear alterations, which can be
      associated with genetic instability. The origin and mechanism of formation of the
      nuclear alterations are largely unknown, with the micronucleus being the most
      well studied alteration. The purpose of this study was to characterize the
      cytoskeleton filaments and to analyze the possible association between nuclear
      alterations and the cytoskeleton in the human lung carcinoma cells HK2 and A549.
      The cytoskeleton analysis was performed by using antibodies against lamin B,
      vimentin, cytokeratin-8, and alpha-tubulin and the secondary antibody labeled
      with FITC. The analysis of the actin filament was made with phalloidin-TRITC. The
      analyses of cytoskeleton were performed from optical sections obtained by
      confocal laser scanning microscopy. Filaments of the cytoskeleton of tumor cells
      present some differences in their distribution pattern and their expression when
      compared with the filaments of normal cells. The HK2 cells presented actin fibers
      arranged either concentrically or in clusters and tubulin filaments arranged
      radially, while in the A549 cells the distribution pattern was similar to that of
      normal cells. The lamin B filaments were the most important to identify nuclear
      alterations. These alterations in cytoskeleton distribution could not be
      associated with nuclear alterations.

PMID- 11449889
TI  - A valid quantitative histochemical technique for assaying cytochrome c oxidase in
      single cells.
AB  - A quantitative histochemical method for assaying cytochrome c oxidase (COX) has
      been validated with two new findings concerning the optimal tissue thickness and
      a suitable substrate. The kinetics of a COX-catalysed reaction coupled to the
      oxidation of diaminobenzidine (DAB) were followed at 37 degrees C in single
      muscle fibres in unfixed sections of mouse gastrocnemius using a real-time image
      analysis system. The optimum composition of the substrate medium for the reaction
      was 0.1 mM reduced cytochrome c, 4 mM DAB, 2% dimethylsulphoxide, 2% polyvinyl
      alcohol and 0.1 mM HEPES buffer, final pH 7.5. The absorbances at 451 nm of the
      final reaction products, DAB polymer oxides, deposited in the intermyofibrillar
      mitochondria increased linearly as a function of incubation time for at least 80
      s after the start of incubation. The initial velocities (v(i)) of the COX
      reaction calculated from the gradients of the linear regression best fits for
      times between 40 and 60 s were reproducible. The v(i) determined in single muscle
      fibres at a saturated concentration of cytochrome c (0.1 mM) were proportional to
      section thickness for thicknesses less than 3 microns, but they decreased
      exponentially when the thickness was greater than 4 microns. Thus, for the
      quantitative assay, unfixed sections 3 microns thick must be used. The Michaelis
      constants (Km) determined for commercial cytochrome c in the range of 20-26
      microM for COX in three types of skeletal muscle fibres of mouse gastrocnemius
      were higher than the corresponding in situ Km (12-13 microM) for reduced
      cytochrome c. However, the Km values for commercial cytochrome c were in good
      agreement with the value previously determined with homogenates of rat hind limb
      muscle. Therefore, reduced cytochrome c is a more suitable substrate for the
      kinetic study and assay of COX in situ.

PMID- 11449890
TI  - A monoclonal antibody against insect CALNUC recognizes the prooncoprotein EWS
      specifically in mammalian cells. Immunohistochemical and biochemical studies of
      the antigen in rat tissues.
AB  - A monoclonal antibody against insect CALNUC was shown to recognize an 85-kDa
      nuclear protein specifically in mammalian cells. Amino acid sequencing of the
      protein purified from rat liver revealed it to be EWS, a prooncoprotein for Ewing
      sarcomas and related tumors. Using the antibody, distribution of EWS was studied
      in rat tissues fixed with 4% paraformaldehyde by immunohistochemical methods. On
      thaw-fixed cryosections or those of perfusion-fixed tissues, almost all cell
      nuclei showed the specific staining. In immersion-fixed tissues, the staining
      unexpectedly disappeared in particular tissues (kidney cortex, liver, etc.),
      although it was recovered by autoclaving the cryosections. Western blotting also
      demonstrated the ubiquitous expression of EWS in the tissues. In extracts from
      the liver, the 85-kDa band rapidly disappeared in a Ca(2+)-dependent manner, but
      never in the testis. The antigen was very labile in kidney homogenates even
      without Ca2+. Biochemical studies with digoxigenin-labeled EWS showed that the
      Ca(2+)-dependent disappearance was associated with upward mobility shifts of EWS.
      These suggested that EWS was ubiquitously expressed in rat tissues, and that the
      antigen was masked in particular tissues during the immersion fixation.

PMID- 11449891
TI  - Immunohistochemical analysis of diethylstilbestrol-induced renal tumors in adult
      male Syrian hamsters: evidence for relationship to peripheral nerve sheath
      tumors.
AB  - Estrogen-induced Syrian hamster kidney tumors (SHKT) are widely used as
      experimental models for the study of hormonal and renal carcinogenesis. In order
      to characterize the direction of differentiation of SHKT, kidney sections of
      diethylstilbestrol (DES)-treated hamsters (1-11 months) were analyzed by
      immunohistochemistry using a panel of lineage-specific markers. The first
      tumorous buds found in animals exposed to DES for 4-6 months exhibited prominent
      S100, Leu-7, and vimentin immunoreactivities. Immunopositivities for neuron
      specific enolase, PGP 9.5, desmin, and glial fibrillary acidic protein were
      mostly detected in medium-sized and large tumors after prolonged exposure to DES
      (> 6 months). All neoplasms, irrespective of the size and the duration of
      treatment, appeared negative for cytokeratin, neurofilaments, synaptophysin, and
      CD99 antibodies. Western blotting confirmed to a large extent the
      immunohistochemical observations. The systematic analysis of serial kidney
      sections by confocal microscopy after double immunostaining for S100 and
      neurofilaments revealed that early neoplastic buds could stem from S100-positive
      cells associated with nerves bundles. Altogether, these observations suggest that
      DES-induced SHKT could be related to malignant peripheral nerve sheath tumor and
      originate from a yet unidentified precursor cell present in the sheath of
      peripheral nerves.

PMID- 11449892
TI  - Procoagulant platelet balloons: evidence from cryopreparation and electron
      microscopy.
AB  - Visualisation of the procoagulant transformation of human platelets has recently
      become possible through use of an in vitro approach combined with fluorescence
      and phase contrast microscopy. Here, we extended these studies to the
      ultrastructural level by employing both rapid freezing/freeze-substitution and
      conventional ambient-temperature chemical fixation for transmission and scanning
      electron microscopy. Procoagulant transformation was only inducible by adhering
      platelets to collagen fibrils or to the collagen-related peptide and exposing
      them to physiological extracellular Ca2+ levels. Under these conditions
      prominent, 2- to 4-micron-wide balloon-like structures were regularly observed,
      regardless of the specimen fixation protocol. In strong contrast to normal
      platelets in their vicinity, the balloons' subcellular architecture proved
      remarkably poor: dilute cytoplasm, no cytoskeleton, only a few, randomly
      distributed organelles and/or their remnants. Cryofixed balloons displayed intact
      and smooth surfaces whereas conventional specimen processing caused plasma
      membrane perforations and shrinkage of the balloons. Our results clearly show
      that neither the balloons themselves, nor their simple ultrastructure reflect
      fixation artefacts caused by inadequate membrane stabilisation. The balloons are
      interpreted as to be transformed and/or fragmented procoagulant platelets. Thus,
      the generation of balloons represents a genuine, final stage of platelet
      ontogenesis, presumably occurring alternatively to aggregate formation.

PMID- 11449893
TI  - [Most of fatalities in childhood are caused by accidents--who cares?].

PMID- 11449894
TI  - [NICE not so nice as the name suggests. Sneaking attempt of therapeutic
      bureaucracy?].

PMID- 11449895
TI  - [Count on your beliefs. Bayes' theorem in diagnosis].
AB  - Bayesian analysis of data finds increasing use in medical statistics, diagnostic
      evaluation and decision analysis. The central element in bayesian analysis is a
      set of mathematical rules for integrated evaluation of prior knowledge and new
      information. In many situations this approach has superior ability to deliver
      dependable updated knowledge and to provide an optimal probability basis for
      decisions. This article (the first of two) presents Bayes' theorem and its
      application in diagnostic work. It is explained how likelihood ratios of
      diagnostic tests interact with the outcome of such tests in the conversion of
      initial information (prior odds) to enhanced information (posterior odds).

PMID- 11449896
TI  - [Poverty and child health in the rich Europe].

PMID- 11449897
TI  - [Toxicologic information through four decades].

PMID- 11449898
TI  - [Toxicologic information center's hotline--well-received and cost-effective for
      the society].
AB  - Our evaluation using postal and interview surveys suggests that the telephone
      hotline service at the Swedish Poisons Information Centre
      ('Giftinformationscentralen') may be cost-effective for society. Advice to
      physicians--which was highly regarded for its speed, competence and applicability
      -was time-saving and facilitated better treatment. Similarly, advice direct to
      households eliminated many unnecessary emergency visits. Indeed, we found that
      the annual costs of running the centre can be completely offset by savings in
      health care resources. Improved outcomes, time savings for individual households,
      and reduced uncertainty for both households and health care staff provide
      additional benefits.

PMID- 11449899
TI  - [Prevention and early diagnosis of cancer. What do we know? What do we think?
      Reports from the Lakardagarna in Orebro].
AB  - Lakardagarna (physician days) in Orebro is an annual course arranged by the
      Orebro Society of Medicine in collaboration with The Swedish Society of Medicine.
      In the year 2000 the title was "Prevention and early diagnosis of cancer. What do
      we know? What do we believe? What do we do?" With general practitioners as the
      target audience, the course covered basic biological science, risk factors,
      screening, ethical questions and the general practitioner's dilemma. This article
      reviews four selected contributions: 1) What is cancer? 2) Possible importance of
      the fetal stage for later risk of cancer; 3) Infections as a cause of cancer; and
      4) Screening for cancer.

PMID- 11449900
TI  - [A case report: young man survived penetrating knife stabs to the heart and
      lung].
AB  - In Sweden, penetrating injuries to the lung and especially to the heart are
      fortunately rare. We hereby present a case-report on a young man who was stabbed
      in the right lung and heart. The paramedics arrived at the scene one minute after
      the alarm and instituted mechanical ventilation and fluid infusion. Ten minutes
      later the young man arrived at the emergency department. By then the patient was
      in deep shock without spontaneous breathing, was darkly cyanotic, showed
      indeterminately palpable pulses and non-reacting pupils. ECG-monitoring showed
      sinus-rhythm. Massive fluid infusion was initiated and the adolescent was
      immediately transported to the operating room. On the way to the operating room
      the patient's heart arrested. A lateral thoracotomy was performed to relieve the
      cardiac tamponade, and internal heart massage was initiated. Injuries to the lung
      and heart were reached through sternotomy. Thanks to prompt initial handling by
      the paramedics and emergency personnel, a trauma-trained senior surgeon and
      rather direct lines of communication at the small hospital, the young man could
      return to ordinary activities with neither physical nor neurological deficit.

PMID- 11449901
TI  - [Grief and care].

PMID- 11449902
TI  - [Screening for lung cancer--expensive and inefficient].

PMID- 11449903
TI  - [Building up-care of patients with chronic pain and ache].

PMID- 11449904
TI  - [Alternative medicine should get its righteous position in health care].

PMID- 11449905
TI  - [One more time on impact factor!].

PMID- 11449906
TI  - [Does the laparoscopy specialist manage the conversion to open laparotomy?].

PMID- 11449907
TI  - Intracellular trafficking of Mycobacterium avium ss. paratuberculosis in
      macrophages.
AB  - The granulomatous enteric lesions of cattle with Johne's disease are composed of
      infected macrophages, and grow by accumulation, re-infection, and expansion of
      macrophage populations in the intestinal wall. We have examined the growth of
      bacteria in macrophages to define characteristics of intracellular trafficking
      for exocytosis, replication, and antigen presentation. Using immunocytochemical
      markers for light, confocal and electron microscopy, we have examined potential
      pathway tropisms using data for bacterial attachment, phagosomal acidification,
      phagolysosomal degradation and apoptosis. Our hypotheses are that pathogenic/wild
      type strains block phagosomal acidification so that the phagosome fails to obtain
      markers of the late phagosome and phagolysosome, and this leads to the
      replication pathway within bacteriophorous vacuoles. Non-pathogenic strains
      appear to be processed to exocytosis, and avirulent mutant strains may be
      degraded and have preference of antigen processing pathways that involve
      transport vesicles bearing MHC II antigens. Pathogenicity in a nude mouse model
      of intestinal infection reveals lesion development and confirms pathway
      preferences of virulent strains for bacteriophorous vacuole formation.

PMID- 11449908
TI  - [Prevalence of the Salmonella plasmid virulence gene "spvD" in Salmonella strains
      from animals].
AB  - Strains of Salmonella isolated from animals in Germany (n = 878) were analysed
      for the presence of the spvD gene ("Salmonella plasmid virulence gene D") by DNA
      DNA hybridization. The spvD gene was only detected in strains of serovars
      Typhimurium (93.3%), Enteritidis (97.1%), and Dublin (100%) as well as in two
      rough strains of Salmonella enterica. Salmonella isolates from mammals carried
      the gene more frequently (cattle 94.0%, horses 92.6%, pigs 73.7%) than those from
      birds (33.3%) or reptiles (4.5%). Due to its high prevalence in epidemiologically
      relevant salmonellae, the virulence factor spvD may represent a sensitive and
      specific target in various serovars for diagnostic or immunization strategies.

PMID- 11449909
TI  - Effects of oligosaccharides on functional parameters of the intestinal tract of
      growing pigs.
AB  - Feeding experiments were carried out in growing pigs using topinambur powder or
      inactivated yeasts as prebiotic additives with an application period of at least
      3 weeks. At the end of the experimental periods the animals were killed and
      segments of the intestinal tract were used for measuring transport physiological
      parameters and for mucin histochemistry. Jejunal epithelia were mounted in Ussing
      chambers for measuring electrical tissue parameters, paracellular permeability
      and short circuit current response to mucosal glucose. Both prebiotics had no
      effects on basal or forskolin stimulated short circuit currents. Total tissue
      conductances tended to be higher in response to both prebiotics. Topinambur
      increased mucosal-to-serosal fluxes of mannitol in the proximal and distal
      jejunum, which could only be demonstrated for the distal jejunum when inactivated
      yeasts were fed. Mucosal application of glucose induced higher current responses
      in jejunal tissues. From histochemistry it could be demonstrated that both
      prebiotics increased the number of ileal goblet cells and the thickness of the
      colonic mucosa.

PMID- 11449910
TI  - [Probiotics: Is there a scientific basis for their effects?].
AB  - Probiotic microorganisms have been used with increasing frequency in nutrition
      and for therapeutic purposes during the last years. Their application is
      generally based upon empirical experiences, since their mode of action has been
      the topic of investigations only recently. It became apparent that probiotics
      exert a wide spectrum of different effects ranging from direct antagonism against
      pathogens to influence upon intestinal epithelium and immune system of the host's
      organism. In this review, the current knowledge is summarized.

PMID- 11449911
TI  - [Genetic typing of German isolates of classical swine fever virus].
AB  - During the last decade several outbreaks of classical swine fever (CSF) occurred
      in Germany in domestic pigs and in wild boar, respectively. Two major epidemics
      which also affected other EU Member States were recorded. To support
      epidemiological investigations genetic typing was applied and virus isolates
      originating from different outbreaks in Germany were assigned to groups and virus
      types. Two genomic regions were selected for the phylogenetic analysis, namely
      150 nucleotides from the 5' non-translated region (5'-NTR) and 190 nucleotides
      from the E2 glycoprotein gene. All German CSF virus isolates of the nineties
      (Group 2) were distinct from former reference strains (Group 1). Within Group 2
      both genomic regions allowed to distinguish three subgroups, namely 2.1, 2.2 and
      2.3. Within subgroup 2.3 five virus types could be discriminated using the 5'-NTR
      sequences. These are 2.3*Uelzen and 2.3*Spreda, mainly with isolates from Lower
      Saxony, as well as 2.3*Rostock, 2.3*Gustrow and 2.3*Spante, mainly with isolates
      from Eastern Germany. Analysis of the E2 gene fragment allowed a better
      discrimination between single isolates, but only two virus types could be
      defined: 2.3*MV/BB, comprising the isolates from Eastern Germany, and 2.3*NI,
      with the isolates from Lower Saxony. Genetic typing allowed to discriminate
      between isolates involved in different CSF epidemics, and was useful for tracing
      the origin and spread of CSF viruses. Due to the close relationship between
      German CSF virus isolates, epidemiological data are a prerequisite for the
      interpretation of the results obtained by genetic typing. In addition, at least
      both genomic regions suggested here should be analysed to determine the identity
      of a new isolate.

PMID- 11449912
TI  - [Case report: Yersinia enterocolitica septicemia in an American minipig].
AB  - A natural, lethal enteritis and septicaemia caused by Yersinia enterocolitica in
      an American Minipig piglet is reported. The isolated strain was identified as
      serotype O:3 and biotype 4. Pathomorphological examination of the animal revealed
      a severe fibrinonecrotic ileitis and typhlocolitis. Pyogranulomatous lesions were
      detected in regional lymph nodes and several organs.

PMID- 11449913
TI  - [Applied anatomy of the distal "vinculum tendinis" in the fetlock tendon sheath
      of the hindlimb in cattle].
AB  - A relatively thick (diameter approximately 2 mm), ropelike (length ca. 20 mm) and
      elastic "Vinculum tendinis" connects--within the fetlock tendon sheath--the
      dorsal side of the deep digital flexor tendon with the dorsal part of the Manica
      flexoria (the communicating band of the Musculus interosseous medius to the
      superficial digital flexor tendon). The extensive fetlock tendon sheath can be
      involved in diseases such as aseptic and septic inflammations. Spreading of these
      inflammations makes in some of these cases the partial resection of the tendon of
      the deep digital flexor muscle and the cutting of these Vincula necessary. The
      results of this contribution, collected from 60 hindlimbs of adult bovines show
      variations in number, length, diameter and extent and the inner structure with
      blood vessels and nerves.

PMID- 11449914
TI  - [Megabacteria-associated proventriculitis in poultry in the state of Brandenburg,
      Germany].
AB  - During the second half of the year 2000, we have diagnosed a megabacterial
      associated proventriculitis in 13 laying hens and 4 cocks from 14 different
      flocks and one turkey. All birds were submitted for necropsy because of
      progressive runting, increased mortality and poor laying performance in the
      herds. Routine diagnostic workup included necropsy, histology, bacteriology,
      parasitology and virology. At necropsy, the proventricular of the birds were
      enlarged. The walls were thickened and the mucosa covered with cloudy, grey-white
      mucus. Petechial haemorrhages and ulcerations predominantly at the proventricular
      ventricular junction and sloughing of the necrotic koilin layer of the
      ventriculus were inconsistently present. Megabacteria (approximately 40-50 by 2-4
      microns, gram-positive to gram-labile, rod-shaped organisms) were present in
      large numbers in touch preparations of the proventricular mucosal surface. In
      some of the preparations, the megabacteria showed a branching pattern similar to
      fungal hyphae. By histopathology, all birds showed moderate to marked, diffuse
      lympho-plasmacytic proventriculitis. Heterophilic exudation was present in the
      terminal portion of the proventriculus, where the greatest numbers of the
      organism were found. Megabacteria were present in the mucus covering the mucosal
      surface and the lumina of the superficial proventricular crypts, occasionally
      invading the luminal epithelium. Megabacterial infection was in general
      associated with other diseases such as avian tuberculosis, salmonellosis,
      coccidiosis, chlamydiosis and various other bacterial and parasitic infections.
      Only in one hen no other concurrent infectious organism was detected. The turkey
      had histomoniasis. Wild birds were regarded as probable source of infection,
      since all affected birds were kept under conditions allowing contact to wild
      birds and we have diagnosed megabacterial infections in wild-living green finches
      earlier.

PMID- 11449915
TI  - Megacolon in pigs due to segmental colon aganglionosis.
AB  - Four pigs, each of about 8 weeks of age were submitted for pathological
      examination because of severe cachexia, combined with an enormous distension of
      the abdomen. In the herd, where these pigs originated from, these clinical signs
      were observed frequently for some period of time and stricture of the rectum was
      suspected. All pigs showed a severe cachexia, and most prominent in all pigs was
      a megacolon with large and distended colon and caecum and stenosis about 30 to 60
      cm cranial of the anus. Tissue specimens were taken from the rectum, from the
      colon cranial and caudal of the stenosis and from the jejunum and examined
      histologically. Ganglia in the intestinal wall were examined
      immunohistochemically by using antibodies recognising neurofilament protein (kD
      200). In all pigs submucosal and myenteric ganglia were absent in the post
      stenotic colon and rectum and in transverse section of the stenosis, whereas in
      the prestenotic colon of all pigs and also in the jejunum ganglia were present.
      Segmental aganglionosis of the colon is also known in humans (Hirschsprung
      disease) and other animal species and is considered as a congenital disorder. We
      also suggest a familiar background of the disease in these pigs.

PMID- 11449916
TI  - [Nerve sheath tumors in cattle: literature review and case report].
AB  - Incidence, clinical signs, pathomorphological findings, differential diagnosis
      and prognosis of bovine nerve sheath tumours are reviewed. Own clinical and
      pathomorphological findings are described in an eight years old cow with a benign
      SCHWANNoma of the eight spinal nerve.

PMID- 11449917
TI  - [Histoplasmosis in two badgers (Meles meles) in northern Germany].
AB  - An infection with Histoplasma capsulatum was diagnosed in two wild badgers (Meles
      meles) in northern Germany, which was predominantly localized in the skin and the
      regional lymph nodes. The yeast-like fungi were identified in tissue sections
      using histological and immunohistological methods.

PMID- 11449918
TI  - AIDS: 20th Anniversary, June 2001.

PMID- 11449919
TI  - FDA changes labeling for opiate addiction drug.

PMID- 11449920
TI  - New vaccine approved for 2 hepatitis viruses.

PMID- 11449921
TI  - Selected highlights from the 7th Annual Conference of the British HIV
      Association.

PMID- 11449922
TI  - Methadone stimulates in vitro infection.

PMID- 11449923
TI  - South Africa kills hope of AIDS drugs.

PMID- 11449924
TI  - Understanding protease inhibitor potency: the intersection of exposure, efficacy,
      and resistance.
AB  - Prescribing antiretrovirals has become increasingly complex, not only because of
      the expanding armamentarium but also because the tools available to measure
      different aspects of drug efficacy are complicated and interrelated. Potency
      cannot be viewed as a single unit of data, such as inhibitory concentration, and
      viral susceptibility to a drug cannot be viewed as a binary choice between
      "sensitive" and "resistant." Rather, both potency and resistance are continums,
      and attempts to quantify them in simple terms are often misleading. At the same
      time, potency and resistance must be considered pieces of a more complex puzzle
      that also involves drug exposure, metabolism, and pharmacokinetics. Appraising
      all of these factors simultaneously is difficult but necessary for the optimal
      care of people with HIV infection.

PMID- 11449925
TI  - Enhancing adherence to HAART: a pilot program of modified directly observed
      therapy.
AB  - Based on the model of directly observed therapy (DOT) for tuberculosis, we
      implemented an uncontrolled pilot program of modified DOT to increase adherence
      to HAART. Participants met every weekday with an outreach worker who observed
      them taking the morning dose of HAART. Thirty-seven patients with a history of
      poor adherence were enrolled and followed for a mean duration of 10 months. The
      program was feasible and well accepted by the participants. Self-reported
      adherence to nonobserved doses improved, and those who remained in the program
      for a year (n = 18) demonstrated a mean 1.53-log decrease from baseline in plasma
      HIV RNA level.

PMID- 11449926
TI  - Abdominal carcinomas mimicking HIV-associated lipodystrophy.
AB  - Two cases of abdominal distention and extremity muscle wasting in HIV-infected
      men who were receiving HAART are reported. In both instances, clinician and
      patient alike were concerned about the possibility of HIV-associated
      lipodystrophy. However, further investigation led to a diagnosis of disseminated
      cancer in both patients.

PMID- 11449927
TI  - Full recovery from severe dilated cardiomyopathy in an HIV-infected patient.
AB  - HIV-related cardiomyopathy is usually seen in persons with advanced HIV disease
      and carries a very poor prognosis. Severe dilated cardiomyopathy necessitating
      hospitalization in the cardiac ICU with vasopressor and ventilator support
      developed in a 44-year-old HIV-infected man with a CD4+ cell count of 552/microL
      and an undetectable plasma HIV RNA level who was treated with didanosine and
      hydroxyurea. During the course of a year, he had full recovery of cardiac
      function. Aggressive intervention is warranted in otherwise healthy HIV-infected
      patients presenting with severe dilated cardiomyopathy.

PMID- 11449928
TI  - Facial wasting.

PMID- 11449929
TI  - Dermatoscopic screening in family practice.
AB  - BACKGROUND: Screening for dermatologic lesions is important in primary care
      medicine and may be enhanced by magnified illuminated video images. Viewing skin
      lesions with a dermatoscopic instrument is very helpful in judging and evaluating
      their characteristics. Both patients and physicians benefit from the improved
      diagnostic yield, possible medical-legal protection, enhanced development of the
      patient-physician relationship, medical practice economic boost, and more
      efficient dermatologic screening. The higher magnification and illuminated view
      theoretically enables the physician to make better decisions and helps convince
      the patient to comply with recommended treatment. METHODS: 57 patients in a
      single private family practice were interviewed before receiving a visual
      dermatology screening examination. The physician then recorded his findings and
      suggested plan. Next, the physician performed a magnified video dermatologic
      examination and once again recorded his findings, plan, and impression of the
      patient's reaction to the recommendations and treatment. RESULTS: 57 patients
      with 79 examination sites demonstrated an increased confidence by both the
      physician and patient with the video examination over the traditional
      dermatologic examination. In addition, several changes in proposed treatment were
      noted following the video examination. CONCLUSIONS: Both the patients and
      physician believed the magnified video dermatologic examination improved
      diagnostic accuracy and increased patient motivation to act on physician
      recommendations.

PMID- 11449930
TI  - AIDS in Delaware: 2000 update.

PMID- 11449931
TI  - Hospitals and the culture of noise: whither the sound of silence?

PMID- 11449932
TI  - Students' and teachers' cognitions about good teachers.
AB  - BACKGROUND: Good teachers have been studied ever since Plato described how
      Socrates taught by asking questions of his audience. Recent findings shed light
      on two characteristics of good teachers: their personality and their ability.
      However, more attention has been paid to teachers' practices and opinions than to
      students' views. AIMS: The study reported here attempted to deepen our
      understanding of what students think about good teachers. SAMPLE: Students of
      four age groups (7, 10, 13, and 16 years of age) and teachers from primary and
      secondary schools were asked to write an essay on the good teacher. METHODS: The
      correspondence between conceptual items in the essays was investigated by
      determining the extent to which they were used in the same essays to describe
      good teachers. RESULTS: Correspondence analysis revealed two dimensions. The
      first dimension reflected the preference of students and teachers for describing
      the good teacher in terms of either personality or ability characteristics. The
      second dimension was interpreted as an orientation in the essays towards either
      attachment to, detachment from or commitment to school and teachers. Students and
      teachers were compared to establish the amount of (dis)agreement about what makes
      a good teacher. Primary school students described good teachers primarily as
      competent instructors, focusing on transfer of knowledge and skills, whereas
      secondary school students emphasised relational aspects of good teachers.
      Teachers, however, considered good teachers in the first place a matter of
      establishing personal relationships with their students. Consequently, primary
      school students and teachers disagreed about the characteristics of good
      teachers. In secondary education, disagreements between teachers and students
      were relatively small. CONCLUSIONS: The research method of collecting free essays
      and utilising correspondence analysis to represent conceptual items and groups of
      participants seems promising as long as a theoretical framework is available to
      interpret the resulting representation of similarities between items and groups
      of participants.

PMID- 11449933
TI  - Task perception as a mediating variable: a contribution to the validation of
      instructional knowledge.
AB  - BACKGROUND: From the perspective of the cognitive mediational paradigm, we focus
      in this study on students' conceptions of the relationship between instructional
      interventions and learning: 'instructional knowledge'. AIMS: Task perception has
      been investigated as a procedural manifestation of instructional knowledge. Four
      research questions directed the study: (1) how do students perceive a task; (2)
      by which structure can the relations between categories of task perception be
      represented; (3) do students differ in their task perception; and (4) is there a
      significant relationship between students' task perception and the learning
      activities they plan and/or execute. SAMPLE: The sample consisted of 149
      university freshmen in educational sciences. METHODS: Students were confronted
      with a concrete task in a natural setting. Correlations were searched for by phi
      coefficient. Hierarchical classes analysis was used to search for hierarchical
      relations and inter-individual differences. Goodman-Kruskal lambda was calculated
      to estimate the association between students' task perception and the learning
      activities they planned and executed. The questionnaire and the design of the
      coding systems were first tried out in a pilot study. RESULTS: Students' task
      perception can be described in 11 categories. Correlations between those
      categories were low, but a simple hierarchical structure was discovered. Students
      can be distinguished according to their task perception into eight groups.
      Finally, the results indicate a statistically significant association between
      students' task perception and the learning activities they plan and execute.
      CONCLUSIONS: The study provides additional evidence to involve 'instructional
      knowledge' and students' task perception as part of it, as mediating variables in
      future research.

PMID- 11449934
TI  - A self-determination approach to the understanding of motivation in physical
      education.
AB  - BACKGROUND: It is widely acknowledged that Physical Education (PE) can play a
      potentially important role in enhancing public health by creating positive
      attitudes toward exercise and by promoting health-related fitness programmes.
      However, these initiatives will have limited success if students are not
      motivated to participate actively in their PE lessons. AIM: A sequence of
      motivational processes, proposed by Vallerand (1997), was tested in this study.
      The sequence has the form 'social factors-->psychological mediators-->types of
      motivation-->consequences'. SAMPLE: Participants were 424 British students aged
      14-16 years from Northwest England. METHOD: Questionnaires were used to measure
      cooperative learning, self-referenced improvement, and choice of tasks (social
      factors), perceived competence, autonomy, and relatedness (psychological
      mediators), intrinsic motivation, identification, introjection, external
      regulation, and amotivation (types of motivation), and boredom, effort, and
      future intention to exercise (consequences). RESULTS: A SEM analysis showed that
      perceived competence was the major psychological mediator. Intrinsic motivation
      was related to positive consequences, whereas external regulation and amotivation
      were predictors of negative consequences. A multisample analysis indicated that
      the model was largely invariant across gender. CONCLUSIONS: The findings
      underline the importance of perceived competence and intrinsic motivation in
      compulsory PE.

PMID- 11449935
TI  - Stress and strain in teaching: a structural equation approach.
AB  - BACKGROUND: School teaching seems to be particularly stressful. The stress model
      of Lazarus and colleagues and its adaptation to educational settings by Kyriacou
      and Sutcliffe is the basis for an analysis of antecedents and consequences of
      teacher stress. AIMS: The first aim was to test the theoretical model of teacher
      stress on a large sample using structural equation statistics (study I). The
      results should then be cross-validated and the model enlarged by additional
      operationalisations (study II). SAMPLES: Heterogeneous samples of German school
      teachers (study I: N = 356, study II: N = 201). METHODS: In study I, standardised
      questionnaires measuring workload and mobbing as stressors, physical symptoms as
      stress reactions, and social support and self-efficacy as moderating variables.
      In addition to these concepts, coping strategies, burnout and absenteeism were
      assessed in study II. RESULTS: The structural equation modelling in study I
      revealed that the predications of the stress model hold true: Workload and
      mobbing lead to stress reactions, whereas principal support reduces the
      perception of workload and mobbing. Global support and self-efficacy moderate the
      relationships between the variables. These results were confirmed in study II and
      the model was enlarged by burnout and coping strategies. With all concepts, 12%
      of the variance of absenteeism can be explained. CONCLUSIONS: Limitations of the
      studies, using cross-sectional data and self-reported measures are discussed.
      Practical implications for improving the situation are provided.

PMID- 11449936
TI  - Collaborative writing: the effects of metacognitive prompting and structured peer
      interaction.
AB  - BACKGROUND: The structured system for peer assisted learning in writing named
      Paired Writing (Topping, 1995) incorporates both metacognitive prompting and
      scaffolding for the interactive process. AIM: This study sought to evaluate the
      relative contribution of these two components to student gain in quality of
      writing and attitudes to writing, while controlling for amount of writing
      practice and teacher effects. SAMPLE: Participants were 28 ten- and eleven-year
      old students forming a problematic mixed ability class. METHODS: All received
      training in Paired Writing and its inherent metacognitive prompting. Students
      matched by gender and pre-test writing scores were assigned randomly to
      Interaction or No Interaction conditions. In the Interaction condition, the more
      able writers became 'tutors' for the less able. In the No Interaction condition,
      the more able writers acted as controls for the tutors and the less able as
      controls for the tutees. Over six weeks, the paired writers produced five pieces
      of personal writing collaboratively, while children in the No Interaction
      condition did so alone. RESULTS: On pre- and post-project analyses of the quality
      of individual writing, all groups showed statistically significant improvements
      in writing. However, the pre-post gains of the children who wrote interactively
      were significantly greater than those of the lone writers. There was some
      evidence that the paired writers also had more positive self-esteem as writers.
      CONCLUSION: The operation and durability of the Paired Writing system are
      discussed.

PMID- 11449937
TI  - Classroom contexts: connections between class size and within class grouping.
AB  - BACKGROUND: There has been a vigorous debate for many years about the educational
      effects of class size differences, but even if differences have an impact on
      pupils' academic progress this still leaves unanswered important questions about
      what mediates the effect. AIMS: This paper is informed by a classroom contextual
      perspective, and examines associations between class size and within class
      groupings (in terms of size and number of groups, adult presence in groups, and
      type of interaction between grouping members). Age differences in these
      relationships are also explored. SAMPLES: The quantitative study is based on
      analysis of 3157 groupings, from 672 Reception, Year 2 and Year 5 classes in 331
      schools. The qualitative study was based on 12 classes in 8 case study schools,
      and questionnaire responses completed by over 100 class teachers. METHODS: Links
      between size of class and within class groupings were examined on the basis of a
      'grouping mapping survey', in which teachers at a given time in the school day
      provided information on group size and number, adult presence, and type of
      interaction between pupils, and complementary qualitative analyses of data from
      teacher-completed questionnaires, and interviews. RESULTS: The number of groups
      in a class increased with the size of the class. Over all three year groups,
      small classes had on average just over three groups, while large classes
      approached six groups. The size of groups in the class decreased with size of
      class. In class sizes over 25, pupils were more likely to be in a large group of
      7-10, while in classes under 25 they were more likely to be in whole class
      groupings. Qualitative analyses showed that teachers felt that groups of 7-10
      pupils had negative educational effects, for example, in terms of the quality and
      quantity of teaching and children's concentration and contribution in groups.
      CONCLUSIONS: Results suggest that the effects of class size can be best seen as
      through the size and number of groups, which will then have implications for
      learning experiences. So while debate about size of class has often been in terms
      of reduced size of class resulting in pupil academic gains, it is also important
      educationally to consider within class grouping size and number, and their
      effects.

PMID- 11449938
TI  - Boys starting school disadvantaged: implications from teachers' ratings of
      behaviour and achievement in the first two years.
AB  - BACKGROUND: Consistent evidence indicates that low socio-economic status (SES)
      acts as an important stressor and vulnerability factor for children's school
      learning. However, specific mechanism(s) of this process are still not well
      understood. AIM: This study was a follow-up of the classroom learning behaviour
      and perceived achievement of low and middle income children after two years at
      school, who had previously been rated soon after starting school. It examined
      whether teachers' ratings displayed predictive stability over that period, and
      whether significant differences evident at age 5 in SES and gender were still
      operative at age 7. SAMPLE: Two samples, of low income (N = 85) and middle income
      (N = 63) children, were rated following school entry (mean age 5 years 3 months)
      and rated again after two years at school. METHOD: The children were rated at
      both points by their regular classroom teachers using the Learning Behaviours
      Scale (Stott et al., 1998) with subscales of Distractible, Apprehensive and
      Uncooperative, together with ratings of academic achievement and their personal
      perception of each child. RESULTS: SES was found to be a very limited predictor
      for the learning behaviour subscale ratings and for teachers' personal
      perceptions at both ages 5 and 7. SES did significantly predict expected Academic
      Achievement at age 5, but this effect disappeared completely by age 7.
      Conversely, within the two defined groups, Low Income boys were found to display
      significantly poorer learning behaviours at age 5, especially in terms of
      distractible behaviour, compared with Middle Income boys and with girls
      generally. This pattern was maintained over the next two years of their
      schooling. The effect of SES was thus demonstrated more powerfully in between
      group differences than by means of regression. The findings emphasised the
      persistence of teachers' initial negative impressions about distractible 'hard to
      manage' boys from low SES families. CONCLUSION: The outcomes of this study
      suggest that low SES boys commenced school significantly disadvantaged by a
      pattern of perceived distractible behaviour in particular, and that this
      perception continued to operate over the next two years of their schooling. Such
      a pattern implied that these boys were perceived by their teachers, from early in
      their school careers, as being demanding and difficult to teach. Once teachers
      gave certain boys a label it appeared to 'stick'. SES per se was thus not the
      main risk factor. It was primarily the effect of boys' greater activity level,
      distractibility, and initial inability to 'settle' to classroom routines, which
      seemed to be particularly associated with certain lower SES child-rearing
      practices. These behaviours had a serious negative impact on the children's
      teachers and the way they responded to them.

PMID- 11449939
TI  - Ability grouping in secondary schools: effects on pupils' self-concepts.
AB  - BACKGROUND: Current pressure on secondary schools to increase ability grouping
      has raised concerns about the impact of setting on pupils' self-concepts.
      Evidence from previous research is conflicting. A multidimensional measure and
      multilevel modelling promise to clarify the effects. AIMS: This paper aims to
      examine the effects of structured ability grouping on year 9 pupils' self
      concepts. SAMPLES: The sample comprises over 3000 year 9 pupils (aged 13-14
      years) in 45 mixed secondary comprehensive schools in England. The schools
      represent three levels of ability grouping in the lower school (years 7 to 9).
      METHODS: Pupils responded to a multidimensional self-concept scale measuring
      academic and general facets of the self-concept. Measures of attainment were
      collected in English, mathematics and science. Multilevel modelling was used to
      examine the effect of the type of school on the general facets of the pupils'
      self-concept and the effects of setting in each curriculum subject on the
      academic facets of the self-concept. RESULTS: Pupils' general self-concept was
      higher in the group of schools with moderate levels of setting. The degree of
      setting in mathematics and science had no effect on the corresponding academic
      self-concepts but setting in English tended to lower the self-concepts of the
      higher attaining pupils and raise the self-concepts of lower attaining pupils.
      Gender differences were consistent with previous research, with boys having
      significantly higher self-concept scores than girls, except in English. These
      findings indicate that the degree of stratification in schools can have an impact
      on adolescents' self-esteem and views of themselves in school.

PMID- 11449940
TI  - Changes in conceptions of learning for indigenous Australian university students.
AB  - BACKGROUND: Conceptions of learning have been investigated for students in higher
      education in different countries. Some studies found that students' conceptions
      change and develop over time while others have found no changes. Investigating
      conceptions of learning for Australian Aboriginal and Torres Strait Islander
      university students is a relatively new area of research. AIMS: This study set
      out to investigate conceptions of learning for Aboriginal and Torres Strait
      Islander university students during the first two years of their undergraduate
      degree courses in three Australian universities. Conceptions for each year were
      compared. Knowing more about learning as conceived by this cultural group may
      facilitate more productive higher educational experiences. SAMPLE: The sample
      comprised 17 students studying various degrees; 11 were male and 6 were female.
      Ages ranged from 18 to 48 years; mean age was 26 years. METHOD: This was a
      phenomenographic, longitudinal study. Individual semistructured interviews were
      conducted each year to ascertain students' conceptions of learning. Conceptions
      for second year were derived independently of those from first year. A
      comparative analysis then took place to determine any changes. RESULTS: These
      students held conceptions of learning that were similar to those of other
      university students; however there were some intrinsic differences. On a group
      level, conceptions changed somewhat over the two years as did core conceptions
      reported by some individual students. Some students also exhibited a greater
      awareness of learning during their second year that resulted in three dimensions
      of changed awareness. CONCLUSIONS: We believe the changed conceptions and
      awareness resulted from learning at university where there is some need to
      understand and explain phenomena in relation to theory. This brought about new
      understandings which allowed students to see their own learning in a relational
      sense.

PMID- 11449941
TI  - The structure of /s/-sequences: evidence from a disordered system.
AB  - This study considers the much-debated markedness and structural status of word
      initial /s/-sequences in English by examining the development of KR (male, age
      3;6) who has a phonological disorder. Three points in time are discussed: (1)
      when all initial consonant sequences are reduced to singletons; (2) when only
      initial /s/-sequences surface correctly; and (3) when all initial consonant
      sequences surface correctly. While these production patterns are common across
      developing systems, few accounts have addressed them in terms of structure or
      markedness. Toward that end, it is argued that KR's /s/-sequences surface as
      adjuncts, rather than complex onsets. This is explained within optimality theory,
      whereby high-ranking markedness constraints prevent complex onsets but not
      adjuncts. The account offers an explanation for consonant sequence asymmetries
      within and across grammars, allowing for differing representations for /s/
      sequences across speakers and for variation exhibited in children's productions.
      A typology of possible grammars is therefore offered, and clinical implications
      are considered.

PMID- 11449942
TI  - Broadening the units of analysis in communication: speech and nonverbal
      behaviours in pragmatic comprehension.
AB  - Recently, much research has explored the role that nonverbal pointing behaviours
      play in children's early acquisition of language, for example during word
      learning. However, few researchers have considered the possibility that these
      behaviours may continue to play a role in language comprehension as children
      develop more sophisticated language skills. The present study investigates the
      role that eye gaze and pointing gestures play in three- to five-year-olds
      understanding of complex pragmatic communication. Experiment 1 demonstrates that
      children (N = 29) better understand videotapes of a mother making indirect
      requests to a child when the requests are accompanied by nonverbal pointing
      behaviours. Experiment 2 uses a different methodology in which children (N = 27)
      are actual participants rather than observers in order to generalize the findings
      to naturalistic, face-to-face interactions. The results from both experiments
      suggest that broader units of analysis beyond the verbal message may be needed in
      studying children's continuing understanding of pragmatic processes.

PMID- 11449943
TI  - Vocabulary development in Italian children: a longitudinal evaluation of
      quantitative and qualitative aspects.
AB  - In this study vocabulary development of a sample of 42 Italian children was
      evaluated through monthly administration of the Italian version of the CDI. Data
      collection started at 1;0-1;1 for 32 children and at 1;3-1;4 for the remaining
      subjects and continued until children's vocabulary reached 200 words. At fixed
      stages of vocabulary size (50, 100 and 200 words), individual differences in
      percentile scores and vocabulary composition were examined. Individual growth
      curves were analysed in order to verify the presence of a vocabulary spurt and
      the type of lexical items which contributed most to rapid acceleration in
      vocabulary growth. Stylistic differences in vocabulary composition were examined
      regarding the 'referential-expressive' distinction, controlling vocabulary size.
      Data have shown that general trends in vocabulary development are quite similar
      to those obtained for other languages using CDI adaptations. Moreover, all
      children in this sample eventually exhibited a vocabulary spurt, even if some can
      be defined as 'late spurters'. The type of lexical items which are learned during
      the spurt depend on both infant vocabulary size and referential score. About 28%
      of infants in this sample were defined 'referential' when their vocabulary size
      was about 50 words, but the stylistic differences disappeared at the 100- and 200
      word stages. Composition of vocabulary did not differ in relation to precocity in
      reaching different stages of vocabulary development. The only exception was that
      infants who reached the 50-word stage first also had a vocabulary with a lower
      proportion of function words.

PMID- 11449944
TI  - Form and function of negation in early developmental Cantonese.
AB  - This study investigated the interface of form and function in the acquisition of
      negation in Cantonese-speaking children. The data, from the Hong Kong Cantonese
      Child Language Corpus, were longitudinal spontaneous samples of eight children
      aged 1;5 to 3;8. The main issues of the study were the sequence of emergence of
      negative markers mou5, m4 and mei6 and the acquisition trend of 11 semantic
      categories of negation in children's expressive language. The acquisition trend
      of the semantic categories matched Bloom's (1970, 1991a) finding that Non
      existence preceded Rejection and Denial.

PMID- 11449945
TI  - Development of syllable structure in English-speaking children with particular
      reference to rhymes.
AB  - This study investigates acquisition of the rhyme using cross-sectional and
      longitudinal data from 14 English-speaking children (aged 1;3-2;0). It focuses on
      4 questions pertaining to rhyme development, which are motivated from current
      theories of prosodic acquisition: 1. Do children make vowel length errors in
      early acquisition?; 2. Do children acquire coda consonants before they learn the
      vowel length contrast?; 3. What consonants are first acquired as codas?; and 4.
      Is there a size constraint such that children's productions are minimally and
      maximally bimoraic? The results indicate that the percentage of vowel length
      errors across all children was low irrespective of the percentage of codas
      produced. In particular, two children produced very few coda consonants and made
      few vowel length errors, suggesting that mastery of vowel length was not
      secondary to coda acquisition. With respect to coda segments, children produced
      voiceless obstruents as codas before sonorants supporting generally the claim
      that obstruents emerge before sonorants in coda position. Children produced coda
      consonants more frequently after short than long vowels consistent with a
      bimoraic size constraint in syllable development. The paper concludes by
      comparing the English findings with cross-linguistic work on vowel length
      acquisition.

PMID- 11449946
TI  - Article use in Spanish-speaking children with specific language impairment.
AB  - The current study analysed article use in Spanish-speaking children with specific
      language impairment who are learning English as a second language. The surface
      hypothesis account of specific language impairment was evaluated in relation to
      the use of articles in these children. Language samples were obtained from 15
      Spanish-speaking children with language impairment and 15 with normal language,
      ages 5;0 to 7;1, matched by age, gender, and school. The percentage of article
      errors was tested between groups with a nonparametric analysis and an analysis of
      covariance with mean length of terminable unit as the covariate. Results revealed
      significant differences between groups on percent of article errors with and
      without MLTU as the covariate. Nonparametric statistics on percent of article
      error types indicated that most errors consisted of omissions and gender
      agreement substitutions. As predicted by the Surface Hypothesis, article errors
      were likely to occur in unstressed definite articles, suggesting that perceptual
      and prosodic processes have some impact on children's production of articles.

PMID- 11449947
TI  - Bilingual signed and spoken language acquisition from birth: implications for the
      mechanisms underlying early bilingual language acquisition.
AB  - Divergent hypotheses exist concerning the types of knowledge underlying early
      bilingualism, with some portraying a troubled course marred by language delays
      and confusion, and others portraying one that is largely unremarkable. We studied
      the extraordinary case of bilingual acquisition across two modalities to examine
      these hypotheses. Three children acquiring Langues des Signes Quebecoise and
      French, and three children acquiring French and English (ages at onset
      approximately 1;0, 2;6 and 3;6 per group) were videotaped regularly over one year
      while we empirically manipulated novel and familiar speakers of each child's two
      languages. The results revealed that both groups achieved their early linguistic
      milestones in each of their languages at the same time (and similarly to
      monolinguals), produced a substantial number of semantically corresponding words
      in each of their two languages from their very first words or signs (translation
      equivalents), and demonstrated sensitivity to the interlocutor's language by
      altering their language choices. Children did mix their languages to varying
      degrees, and some persisted in using a language that was not the primary language
      of the addressee, but the propensity to do both was directly related to their
      parents' mixing rates, in combination with their own developing language
      preference. The signing-speaking bilinguals did exploit the modality
      possibilities, and they did simultaneously mix their signs and speech, but in
      semantically principled and highly constrained ways. It is concluded that the
      capacity to differentiate between two languages is well in place prior to first
      words, and it is hypothesized that this capacity may result from biological
      mechanisms that permit the discovery of early phonological representations.
      Reasons why paradoxical views of bilingual acquisition have persisted are also
      offered.

PMID- 11449948
TI  - Parental reports of 'MAMA' sounds in infants: an exploratory study.
AB  - This study investigated the use of 'mama' or similar sounds (collectively
      referred to as 'MAMA') by 75 infants less than six months of age. Parents were
      directed to listen for 'MAMA' sounds and to note the sounds made, the age of
      onset, whether the sounds appeared to be directed to any person or persons and
      whether they appeared to have a purpose. 'MAMA' began at a mode of two months,
      range two weeks to five months, was usually part of a cry, and was always
      interpreted as a 'wanting' sound. Most parents thought that the infant wanted
      some form of attention, but a minority thought it indicated hunger. Responses to
      a Structured Response Protocol indicated that some infants uttering 'MAMA' were
      satisfied if a favourite caretaker approached and paid attention to them while
      the remainder were satisfied if they were both paid attention to and picked up.
      The 'MAMA' cry appears to promote attention-giving behaviour by parents and other
      caretakers.

PMID- 11449949
TI  - Productive inventory and case/agreement contingencies: a methodological note on
      Rispoli (1999).
AB  - Rispoli (1999) suggests that previous studies arguing for a contingency between
      the case of subject pronouns and the presence/absence of verbal agreement in the
      acquisition of English (e.g. Schutze, 1997) suffer from methodological problems,
      and presents new data that fail to support earlier findings. I show that
      Rispoli's methodology unnecessarily biases his study against finding the
      predicted contingencies: it fails to take account of children's productive
      lexical inventory of pronoun forms. As a result, syntactic versus morphological
      sources of error fail to be distinguished. I explain why this distinction is
      crucial within the AGR/Tense Omission Model, and clarify its predictions.

PMID- 11449950
TI  - Children's judgements about intentionally and unintentionally broken promises.
AB  - Astington (1988) found that seven- to nine-year-olds often fail to distinguish
      between promises and predictions when judging the utterances of characters in
      simple stories. Instead, these children attend only to the outcome of the story
      (i.e. whether the promised event occurred) when deciding whether a promise has
      been made and, to a lesser extent, when deciding whether the speaker is
      responsible for the outcome. The purpose of the present study was to examine
      whether seven- to nine-year-olds (a) vary their judgements of responsibility
      according to the reason that the promised action was not completed, and (b)
      recognize that an unfulfilled promise is a promise regardless of whether the
      speaker's failure is unavoidable or intentional. Seven-year-olds, nine-year-olds,
      and adults were asked to make promise and responsibility judgements for two story
      types: stories in which the promiser intentionally failed to fulfill his or her
      promise and stories in which an unforeseen event prevented the promiser from
      fulfilling the promise. Participants at all ages assigned responsibility
      correctly across both story types. In making promise judgements, however, the
      seven-year-olds' decisions about promises reflected a misguided attention to the
      outcome of a promise or the obstacle to its fulfillment. The nine-year-olds
      recognized that an unfulfilled promise is a promise but only when there was a
      clear reason for the speaker's failure to fulfill his or her obligation. We
      suggest that children consider only sincere promises to be instances of promising
      and make inferences about speaker sincerity by looking to external factors in the
      communicative context.

PMID- 11449951
TI  - Young children and the say/mean distinction: verbatim and paraphrase recognition
      in narrative and nursery rhyme contexts.
AB  - Children's ability to distinguish between the text, what was said, and the
      intentional structure, what was meant, was interrogated by means of verbatim and
      paraphrase questions in two types of discourse, narratives and nursery rhymes.
      Three- to seven-year-olds participated (n = 119, mean age 5.1). There was an
      interaction between the type of discourse and the younger children's ability to
      separate wording from intentional structure. In the narrative form they had
      difficulty rejecting true paraphrases when asked to focus on wording, while in
      the nursery rhyme form the difficulty was accepting a true paraphrase when asked
      to focus on intention.

PMID- 11449952
TI  - Evaluation of donor arm disinfection techniques.
AB  - BACKGROUND AND OBJECTIVE: To validate a standardized optimal national procedure
      for donor arm disinfection. MATERIALS AND METHODS: A direct swabbing and plating
      technique was used to enumerate bacteria present on the arm pre- and
      postdisinfection. Twelve donor arm disinfection techniques were evaluated.
      RESULTS: The Medi-Flex Adapted method, consisting of a two-stage process with an
      initial application of isopropyl alcohol followed by tincture of iodine, produced
      the best arm disinfection. A percentage reduction in bacterial counts of 99.79%
      (logarithmic reduction of 2.67) was obtained. Postdisinfection, 70% of donors had
      bacterial counts of zero, and 98% had counts of 10 or less. CONCLUSION: The Medi
      Flex disinfection method offers the English National Blood Service a validated,
      optimal 'best practice' disinfection technique and should contribute
      significantly to the reduction in risk of transmission of bacteria by
      transfusion.

PMID- 11449953
TI  - Human T-cell leukaemia/lymphoma virus risk may be enhanced in some selected donor
      populations.
AB  - BACKGROUND AND OBJECTIVES: Certain patient ethnic groups may require blood
      components from donors under-represented in the UK donor population. Selective
      recruitment of Afro-Caribbean donors is therefore necessary but was considered to
      pose an increased risk of human T-cell leukaemia/lymphoma virus (HTLV) infection.
      To assess this a seroprevalence study of HTLV was undertaken in Afro-Caribbean
      and Caucasian donors. MATERIALS AND METHODS: Sera from 1100 Afro-Caribbean and
      1100 Caucasian donors were tested for antibody to HTLV. Reactive samples were
      confirmed for specificity using an algorithm comprising two additional assays and
      polymerase chain reaction (PCR) where possible. RESULTS: Six Afro-Caribbean
      donors (0.55%) were considered to be infected with HTLV I. CONCLUSION: Donor
      selection in this case caused a significantly elevated prevalence of HTLV
      infection and serves as a warning of the need for care in the design of policies
      for selective donor recruitment.

PMID- 11449954
TI  - Solvent/detergent treatment does not alter the tolerance or uptake of human
      normal immunoglobulin for intramuscular injection.
AB  - BACKGROUND AND OBJECTIVES: The tolerability and pharmacokinetics of a
      solvent/detergent-treated intramuscular immunoglobulin were compared with those
      of the standard product. MATERIALS AND METHODS: Single, 750-mg intramuscular
      (i.m.) injections were administered to a total of 36 healthy individuals: 23 in a
      double-blind trial and 13 in an open trial. Changes in specific serum hepatitis A
      and hepatitis B antibodies were monitored for a period of up to 3 months
      postinjection. RESULTS: No serious adverse reactions were reported, and the
      bioavailability of the solvent/detergent-treated preparation was equivalent to
      that of the standard i.m. immunoglobulin. CONCLUSION: There is no evidence that
      solvent/detergent treatment alters the pharmacokinetics or tolerance of human
      normal immunoglobulin, but it offers additional assurance against potential virus
      transmission.

PMID- 11449955
TI  - Tetanus antibody levels of female volunteers after injection with
      solvent/detergent-treated human tetanus immunoglobulin (Tetabulin S/D).
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to analyse the increase of
      antitetanus titre in volunteers following injection with human tetanus
      immunoglobulin (HTI). MATERIALS AND METHODS: Twelve females with tetanus antibody
      titres of < or = 0.05 international units (IU)/ml were injected with 500 IU of
      human tetanus immunoglobulin (Tetabulin S/D). The tetanus antibody titres were
      determined before injection, and after 30 h, 48 h and 4 days. RESULTS: A fast and
      sustained increase of protective tetanus antibody levels was observed in 10 of 12
      volunteers. No adverse events related to the study drug were reported.
      CONCLUSIONS: HTI confers rapid and effective immunity to tetanus.

PMID- 11449956
TI  - Haematopoietic stem and progenitor cells in human term and preterm neonatal
      blood.
AB  - BACKGROUND AND OBJECTIVES: Whilst cord blood (CB) contains a significant number
      of haematopoietic stem and progenitor cells suitable for bone marrow
      transplantation, levels of these cells are very low in the adult circulation. In
      previous studies, we demonstrated that stem and progenitor cells are present in
      neonatal blood (NB) and reported the first sibling transplant using a combination
      of CB and NB for a patient with beta-thalassaemia major. However, our preliminary
      data showed that the number of CD34+ cells decreased rapidly in the peripheral
      blood of neonates soon after birth. To further investigate the mechanism of the
      change of stem and progenitor cells in NB, we measured the steady-state levels of
      CD34+ cells, early progenitor subsets and the expression of adhesion molecules,
      in term and preterm neonates. MATERIALS AND METHODS: NB was collected serially
      from infants at 2, 4, 6, 8, 24 and 48 h after birth and was analysed by three
      colour flow cytometry. RESULTS: Our results demonstrated that the number of CD34+
      cells rapidly decreased in term NB, particularly during the first 2-6 h of life,
      by 29.2 +/- 5.55% (P = 0.0003) in absolute counts/ml. A decrease was observed in
      all subsets of CD34+ cells studied, including the CD33+, CD71+, CD62L+ and CD49d+
      populations. In contrast, the CD34+ cell number increased in preterm infants in
      the first 8 h of life, before starting to decrease. Significant inverse
      correlations were observed between gestational age and levels of CD34+ cells (P =
      0.0065, 4-h collection time-point). CONCLUSION: Our study suggests that changes
      in the levels of CD34+ stem and progenitor cells in NB might be triggered by
      parturition and affected by the gestational age. Our findings confirmed that if
      targeted as a supplementary source of stem and progenitor cells to CB for
      transplantation, NB should be collected as soon as possible after birth.

PMID- 11449957
TI  - Bacteria-induced release of white cell--and platelet-derived vascular endothelial
      growth factor in vitro.
AB  - BACKGROUND AND OBJECTIVES: Poor prognosis after resection of primary colorectal
      cancer may be related to the combination of perioperative blood transfusion and
      subsequent development of infectious complications. White blood cell--and
      platelet-derived cancer growth substances, including vascular endothelial growth
      factor (VEGF), may be involved in this process. Therefore, we studied the in
      vitro release of VEGF from white blood cells and platelets stimulated by
      bacterial antigens and supernatants from stored red cell components. MATERIALS
      AND METHODS: Eight units of whole blood (WB) and eight units of buffy-coat
      depleted red cell (SAGM) blood were donated by healthy blood donors.
      Subsequently, half of every unit was leucocyte depleted by filtration, and all 32
      half-units were stored under standard conditions for 35 days. Just after storage,
      and on days 7, 21 and 35 during storage, aliquots of the supernatants were
      removed from the units and frozen at -80 degrees C. WB from other healthy donors
      was stimulated for 2 h with sodium chloride (controls), with Escherichia coli
      lipopolysaccharide (LPS) alone, or with LPS plus supernatants from the non
      filtered or prestorage leucofiltered WB units (diluted 1:10), or from non
      filtered or prestorage leucofiltered SAGM blood units (diluted 1:20) stored for
      0, 7, 21, or 35 days, respectively. Similar assays were performed using
      Staphylococcus aureus-derived protein A as a stimulatory antigen. The
      concentration of VEGF was determined in supernatants from stored blood and in
      assay supernatants by using enzyme-linked immunosorbent assay (ELISA). RESULTS:
      The concentration of VEGF increased significantly (P < 0.0001) in a storage time
      dependent manner in non-filtered WB and SAGM blood, while the increase was
      abrogated by prestorage leucofiltration. The supernatant concentration of VEGF
      was significantly increased in LPS-stimulated (P = 0.002) and in protein A
      stimulated (P < 0.0001) assays compared with controls. Addition of supernatants
      from stored, non-filtered WB or SAGM significantly increased the assay
      supernatant VEGF concentration storage-time dependently (P = 0.006) in LPS
      assays. In protein A assays, only supernatants from non-filtered WB significantly
      increased the assay supernatant VEGF concentration storage-time dependently (P =
      0.022). This additional effect by supernatants from stored blood components was
      not observed with prestorage leucofiltered blood. CONCLUSIONS: Extracellular VEGF
      may accumulate in non-filtered red cell components, but this can be prevented by
      prestorage leucocyte depletion using filtration. In addition, bacterial antigens
      appear to induce release of VEGF from white blood cells and platelets. Addition
      of supernatants from stored, non-filtered WB or SAGM blood may increase the VEGF
      levels in a storage time-dependent manner, while prestorage leucofiltration may
      prevent further increase by supernatants.

PMID- 11449958
TI  - An anti-idiotopic antibody-based enzyme-linked immunosorbent assay for the
      quantification of the monoclonal anti-D BRAD-5.
AB  - OBJECTIVES: We aimed to develop an anti-idiotopic antibody-based enzyme-linked
      immunosorbent assay (ELISA) to quantify human monoclonal anti-D using BRAD-5 as a
      model system. MATERIALS AND METHODS: One of the anti-idiotopic antibodies 2E6 was
      used to capture BRAD-5 with the other anti-idiotopic antibody 3B1 biotinylated
      for detection. RESULTS: The assay developed can detect BRAD-5 at < 2 ng/ml. Assay
      interference caused by heterophilic antibodies in some human sera was removed by
      preincubation with bovine serum. The assay is reproducible with intra- and inter
      assay coefficient of variation (CV) < 10%. CONCLUSION: This ELISA should prove of
      benefit in developing a monoclonal anti-D for prophylactic use.

PMID- 11449959
TI  - The use of the computer cross-match.

PMID- 11449960
TI  - International Society of Blood Transfusion Working Party on Terminology for Red
      Cell Surface Antigens.

PMID- 11449961
TI  - [DNA microarrays in biomedical studies].

PMID- 11449962
TI  - [Initiation of chromosome replication in prokaryotes and eurkaryotes].

PMID- 11449963
TI  - [Organization and evolution of the yeast Saccharomyces cerevisiae genome and the
      problem of orphan open reading frames].

PMID- 11449964
TI  - [Interrelationship between mitochondrial and cytoplasmic translation in the
      Saccharomyces cerevisiae yeast].

PMID- 11449965
TI  - [Disorder of G1 phase control of the cell cycle during oncogenesis].

PMID- 11449966
TI  - [Glutathione: unusual functions of the common tripeptide].

PMID- 11449967
TI  - [Tuftsin--endogenous immunomodulator].

PMID- 11449968
TI  - [Does calcyclin, a Ca2+ ion binding protein, play a similar role as calmodulin?].

PMID- 11449969
TI  - [MUC1 mucin it's significance in neoplastic processes].

PMID- 11449970
TI  - [Biochemistry in the new millennium].

PMID- 11449971
TI  - [Mechanisms of long-term synaptic depression in the hippocampus].
AB  - Long-term depression (LTD) was studied in hippocampal slices obtained from
      neonatal rats at the synapses between CA3 and CA1 pyramidal neurons. The
      induction of the LTD required pairing of Ca2+ influx into the postsynaptic CA1
      neuron through voltage-gated Ca2+ channels with activation of metabotropic
      glutamate receptors. The expression of this form of LTD is at least partly
      presynaptic, suggesting the need for a retrograde messenger. We present evidence
      that arachidonic acid might serve such a function. Thus applications of
      arachidonic acid simulate LTD whereas blockade of arachiidonic acid release
      inhibits LTD.

PMID- 11449972
TI  - [Long-term potentiation of AMPA- and NMDA-components of minimal postsynaptic
      currents in CA1 area of the rat hippocampus].
AB  - Excitatory postsynaptic currents (EPSC) were recorded from pyramidal neurons of
      the rat hippocampal slices as well as the AMPA and NMDA components. A strong
      enough correlation between the amplitudes of the components provided a reliable
      evidence of their generation by the same synapse. Both components revealed
      similar LTP following afferent tetanisation. The data obtained do not support
      postsynaptic mechanisms of the LTP maintenance but suggest that increased
      presynaptic release represents a basic mechanism of the early LTP maintenance.

PMID- 11449973
TI  - [The leading role of mitochondrial depolarization in the mechanism of glutamate
      induced disorder in Ca(2+)-homeostasis].
AB  - Digital fluorescence imaging techniques were employed to monitor changes in the
      cytoplasmic Ca2+ concentration and mitochondrial potential in fura-2 AM or
      rhodamine-123 loaded individual cerebellar granule cells during and following the
      Glu exposure. The data obtained suggests that the MD-induced blockade of the
      mitochondrial Ca2+ uptake and a reversal of the mitochondrial ATP-synthase play a
      critical role in the mechanism of the glutamate-induced disorder of neuronal Ca2+
      homeostasis.

PMID- 11449974
TI  - [Effect of noradrenaline on the amplitude and temporal parameters of multiquantal
      currents and on the kinetics of evoked quantal secretion of a transmitter].
AB  - Noradrenaline caused a significant increase of the multiquantal endplate currents
      (EPC) amplitude, the EPC rising phase/the rising phase of miniature EPC ratio
      diminishing, at that. Noradrenaline seems to synchronise the process of quanta
      secretion in the EPC generation. Thus when a single stimulation of motor nerve
      results in release of several tenths of a transmitter, noradrenaline may increase
      the multiquantal EPC amplitude through synchronising of the transmitter release
      involved in the generation.

PMID- 11449975
TI  - [Synthesis and release of N-acetylaspartyl glutamate (NAAG) in medial giant axons
      in crayfish].
AB  - Studies of crayfish Medial Giant nerve Fiber suggested that glutamate (GLU)
      released from the axon during action potential generation initiates metabolic and
      electrical responses of periaxonal glia. This investigation sought to elucidate
      the mechanism of GLU appearance extracellularly following axon stimulation.
      Axoplasm and periaxonal glial sheath from nerve fibers incubated with
      radiolabelled L-GLU contained radiolabeled GLU, glutamine (GLN), GABA, aspartate
      (ASP), and NAAG. Total radiolabel release was not altered by electrical
      stimulation of nerve cord loaded with [14C]-GLU by bath application or loaded
      with [14C]-GLU, [3H]-D-ASP, or [3H]-NAAG by axonal injection. However,
      radioactivity distribution among GLU and its metabolic products in the
      superfusate was changed, with NAAG accounting for the largest fraction. In axons
      incubated with radiolabeled GLU, the stimulated increase in radioactive NAAG in
      the superfusate coincided with the virtual clearance of radioactive NAAG from the
      axon. The increase in [3H]-GLU in the superfusion solution that was seen upon
      stimulation of nerve bathloaded with [3H]-NAAG was reduced when beta-NAAG, a
      competitive NAALADase inhibitor, was present. Together, these results suggest
      that some GLU is metabolized to NAAG in the giant axon and its periaxonal glia
      and that, upon stimulation, NAAG is released and converted to GLU by NAALADase. A
      quisqualate-, beta-NAAG-sensitive NAALADase activity was detected in nerve cord
      homogenates. Stimulation or NAAG administration in the presence of NAALADase
      inhibitor caused a transient hyperpolarization of the periaxonal glia comparable
      to that produced by L-GLU. The results implicate N-acetylaspartylglutamate (NAAG)
      and GLU as potential mediators. of the axon-glia interactions.

PMID- 11449976
TI  - [Effect of glutamate on spontaneous secretion of acetylcholine in the nerve
      muscle synapse in rats].
AB  - In rats, glutamate was shown to exert no effect on the mean frequency, character
      of interstimuli distribution, amplitude and temporal parameters of the miniature
      EPPs. Glutamate suppressed nonquantal release. The glutamate effect depended on
      its concentration and was abolished by blockade of NMDA receptors, NO-synthase
      inhibitoin, and NO molecules binding by haemoglobin in extracellular medium.
      Glutamate seems to modulate the nonquantal acetylcholine secretion by initiation
      of the NO synthesis in muscle fibres via activation of the NMDA receptors.

PMID- 11449977
TI  - [Effect of endogenous nitric oxide on the nerve-muscle synapse function].
AB  - The nitric oxide (NO) precursor L-arginine was found to decrease the amplitude
      and the quantum content of the EPPs and to increase the amplitude of the AP third
      deflection in the frog neuromuscular junction of the m. cutaneous pectoris
      preparation. Inhibitor of the NO synthase NG-nitro-L-arginine methylester exerted
      opposite effects. The data obtained suggest that endogenous NO is produced in the
      neuromuscular synapse area and can modify the work of potassium ion channels.

PMID- 11449978
TI  - [Effect of carbacholine on proximal and distal regions of motor nerve terminals
      in the frog].
AB  - Carbacholine depressed postsynaptic currents in the frog m. sartorius leaving
      intact presynaptic currents in proximal and distal portions of the motor nerve
      ending. The carbacholine depressing action was followed by an increase in the
      time gap between the beginning of presynaptic depolarisation and subsequent
      quantal release. This effect was considerably more obvious in the distal portions
      of the nerve endings. Effect of extracellular potassium was evident in a
      diminishing of presynaptic currents due to membrane depolarisation. The data
      obtained suggest that carbacholine presynaptically depresses synaptic
      transmission via metabotropic cholinergic receptors controlling the time course
      of the transmitter release.

PMID- 11449979
TI  - [Disinhibitory zone of the striate neuron receptive field and its sensitivity to
      the cross-like shape].
AB  - Sensitivity of 84 neurones to presentation of cross-form figures was studied in
      cats as well as the lever length function prior to and after stimulation of the
      RF disinhibitory zone. Responses to lever length of the cross-sensitive cells
      were augmented in simultaneous stimulation of the RF. The data obtained suggest
      involvement of the end inhibition and its blocking by a side-disinhibitory zone
      of the RF.

PMID- 11449980
TI  - [Induction by ethanol of 'phenomenon of switching estrogen effect' and its
      correction].
AB  - Drinking of 5% ethanol in combination with estradiol induced genotoxic (G)
      changes in the rat uterine tissue. The changes could be prevented by N
      acetylcysteine or melatonin. The data obtained suggest that ascorbic acid and
      alpha-tocopherol may be recommended in combination with N-acetylcysteine for
      repair of estrogen effect switching phenomenon.

PMID- 11449981
TI  - [Response of the serotoninergic brain system to social stress of various duration
      in male mice C57BL/6J and CBA/Lac].
AB  - The effects of social stress caused by experience of defeats in mice during 3 or
      10 consecutive days of intermale confrontations on serotonergic brain activity (5
      HT, 5-HIAA levels and 5-HIAA/5-HT ratio) in some brain regions of CBA/Lac (CBA)
      and C57BL/6J (C57) inbred mice have been studied. It was revealed the significant
      changes in 5-HT methabolism in the brain regions of defeated mice (losers) of CBA
      strain after 3 intermale confrontations. However, after 10 days of social stress
      these changes (excluded amygdala) turned to the control measures testifying to
      the adaptive mechanisms of serotonergic system in CBA losers. In C57 strain, the
      three-day social stress produced the mild changes in the brain serotonergic
      activity both quantitatively as well as qualitatively. Nevertheless, losers
      subjected to ten-day intermale confrontations had more expressed changes in 5-HT,
      5-HIAA levels of 5-HIAA/5-HT ratios in the brain regions studied. It seems that
      long lasting social stress induced the development of disbalance of the brain
      serotonergic activity in C57 losers: it was shown the hyperactivity in the
      hypothalamus and hypoactivity in the amygdala and nucl. accumbens. Apparently,
      this cause leads to the development of the pronounced anxiety shown earlier in
      this mouse strain.

PMID- 11449982
TI  - [Effect of various concentrations of corticoliberin on long-term potentiation in
      slides of the rat olfactory cortex].
AB  - Perfusion of the rat olfactory cortex slices with 1 mcM corticotropin-releasing
      factor (CRF) increased the rate of initiation of the posttetanic potentiation.
      The latter had a shorter supporting phase than in the control. With the
      perfusion, with 0.1 mcM the potentiation had a longer supporting phase than in
      the control.

PMID- 11449983
TI  - [Characteristics of contractile properties of the cat skeletal muscle after
      sympathetic denervation].
AB  - Twitching and tetanus were registered during stimulation in the cat desympathised
      m. semitendinosus, similar to those occurring in the motor units during
      thermoregulatory tone. The contractile responses were greater in the early
      desynpathisation phase. By the 14th day, the contractile responses became similar
      to those of the control.

PMID- 11449984
TI  - [Method for estimation of kinetics of evoked secretion of mediator quanta
      determining generation of multiquantal current in the motor endplate].

PMID- 11449985
TI  - A microstructural study of spinal cord edema.
AB  - The experimental spinal cord edema was produced in a cat by the infusion method
      of Marmarou. Horseradish peroxidase (HRP) dissolved in autoserum of a cat was
      used as a tracer. After laminectomy, a 30-gauge needle was inserted into the
      intumescentia cervicalis. A total amount of 20 microliters of a tracer was
      infused at a rate of 10 microliters/hr. The structural features were studied
      immediately and 3 days after infusion. Immediately after infusion, HRP was noted
      in the infused white and gray matters. Though the perivascular space in the white
      matter at the infused site was widely distended and filled with HRP, the space in
      the gray matter was not distended but filled with HRP. HRP which was observed
      along vessels led to the surface of the spinal cord. Swelling of astrocyte was
      not observed. Three days after infusion, the extracellular space and the
      perivascular space in the infused white matter were still expanded but were not
      filled with HRP. The fine structural features were similar to the findings as
      seen in Marmarou's infusion type of brain edema. Using this model, it seems to be
      feasible to study the resolution process of spinal cord edema.

PMID- 11449986
TI  - Vasogenic oedema and brain infarction in an experimental penumbra model.
AB  - The aim of this study was to modify the photochemical stroke model of Watson et
      al. [23] so as to make possible microscopical investigation of the so-called
      penumbra, a tissue zone at risk that surrounds an infarction. The idea was to
      minimize photochemical challenge to endothelial membranes in such a way that
      thrombotic vascular obstruction is avoided but destabilization of the blood-brain
      barrier is still obtained. Morphological examination of the challenged area
      revealed open blood vessels, overt blood-brain barrier leakage over the entire
      area, severely swollen glial cells and structurally intact neurons. The lesion
      expanded over time due to progressive extravasation, formation of perivascular
      edema and consequent development of secondary ischemia through mechanical
      compression and microvascular congestion. In contrast to a photothrombotic
      infarct, in which the ischemic insult is more severe and blood vessels are
      completely congested by aggregated platelets, with this approach blood flow is
      partially preserved. In this way, an ischemic penumbra is created that mimics
      pathologic conditions secondary to stroke and trauma. The model may be useful in
      studying effects of drugs on pathologic phenomena that are characteristic of a
      penumbra, e.g. vasogenic and cellular edema, inflammation and infarction.

PMID- 11449987
TI  - Effects of chronic deep hypoxia on the expression of nitric oxide synthase in the
      rat brain.
AB  - Experimental studies in extreme hypoxic conditions affecting the brain have been
      performed mainly in acute but not chronic models. Twenty rats were housed and
      exposed to decreasing concentrations of oxygen (from 21% to 7% over 130 days) and
      ten normal rats were used as control. Paraffin slices from representative
      sections containing cerebral cortex, cerebellum, striatum, hippocampus, thalamus
      and hypothalamus were incubated with antisera against nitric oxide synthase.
      Cortex and striatum showed small randomly distributed positive neurons with
      bipolar features, in greater numbers in the hypoxic group (p < 0.02). The
      granular layer of the cerebellum showed a strongly positive rim around some cell
      nuclei. Purkinje cells were immunopositive in hypoxic rats. Hipoccampal, thalamic
      and hypothalamic nuclei showed no quantitative differences in the number of
      positive neurons. The increased number of blood vessels and their dilation
      observed in some brain regions in hypoxic rats, mainly in ventral striatum, lead
      us to hypothesise that NOS may be overexpressed and act at these sites as
      vasomodulator and/or mediator of secondary cell injury affecting selective
      neuronal populations. We conclude that prolonged periods of adaptation to deep
      hypoxia reduces the effect of hypoxia on the upregulation of NOS in the brain
      tissue.

PMID- 11449988
TI  - Adrenergic mediation of TNF alpha-stimulated ICAM-1 expression on human brain
      microvascular endothelial cells.
AB  - Adrenergic innervation derived from locus ceruleus has been implicated in
      regulating BBB permeability and inflammatory responses associated with
      neurological disorders. This report demonstrates that adrenergic agents attenuate
      the tumor necrosis factor-alpha (TNF alpha)-induced expression of intercellular
      adhesion molecule-1 (ICAM-1) on cerebral microvascular endothelial cells (HBMEC)
      derived from human brains. HBMEC were incubated with isoproterenol (1-10 microM)
      alone or in the presence of propranolol (10 microM) for 30 min followed by the
      addition of various concentrations of TNF alpha. ICAM-1 expression on cultured
      HBMEC was dose-dependently upregulated by TNF alpha. Incubation with
      isoproterenol significantly reduced levels of ICAM-1 expression indicating the
      possible involvement of adrenergic agents on ICAM-1 expression. Treatment with
      propranolol (beta 1/beta 2-adrenergic antagonist) and butoxamine (beta 2
      adrenergic antagonist), but not atenolol (beta 1-adrenergic antagonist) reversed
      this inhibitory effect. Isoproterenol also dose-dependently stimulated cAMP
      production (assayed by RIA) by HBMEC; propranolol treatment abolished this
      effect. These data show that the beta 2-adrenergic receptor/cAMP pathway may be
      partly involved in TNF alpha-stimulated ICAM-1 expression and indicate the
      possible involvement of adrenergic mediation of capillary function including BBB
      integrity.

PMID- 11449989
TI  - Time course of apoptotic cell death after experimental neurotrauma.
AB  - Traumatic or ischemic brain injury may give rise to the development of secondary
      brain damage. In the present study the time course of TUNEL staining which is
      widely used to delineate apoptotic reaction pattern was followed after
      experimental neurotrauma in order to test the hypothesis that apoptotic cell
      death may be involved in the development of secondary brain damage. Neurotrauma
      was induced in male Wistar rats by applying a cold probe to the exposed dura over
      the temporo-parietal cortex. Animals were sacrificed between 1 and 72 hours after
      trauma and coronal sections prepared from the lesioned area and adjacent tissue.
      The TUNEL staining was employed to detect DNA-fragmentation and conventional HE
      staining of sequential slices to delineate the extent of the lesion. Occurrence
      of positively stained cells was detected by a computer-based quantification
      system and stored on hard disk. TUNEL-positive nuclei were observed as early as
      one hour after lesion and peaked at 3 hours. There after, the number of cells
      detected decreased steadily. Histological examination revealed two different
      types of morphology in TUNEL-positive cells. A small proportion termed type I
      cells displayed additional signs of apoptotic cell death such as nuclear
      condensation and fragmentation while type-II were considered to undergo necrotic
      cell death. Thus, TUNEL staining proved to be an unspecific marker of apoptotic
      cell death in the present study. Nevertheless, the data suggest that apoptotic
      cell death does not contribute substantially to the final extent of cold induced
      brain tissue damage.

PMID- 11449990
TI  - The permissive nature of blood brain barrier (BBB) opening in edema formation
      following traumatic brain injury.
AB  - The contribution of blood brain barrier opening to traumatic brain edema is not
      known. This study compares the course of traumatic BBB disruption and edema
      formation, with the hypothesis that they are not obligately related. Sprague
      Dawley rats were divided into three groups: Group A (n = 47)--Impact Acceleration
      (IAM); Group B (n = 104)--lateral cortical impact (CCI); Group C (n = 26)--IAM +
      hypoxia & hypotension (THH). BBB integrity was assessed using i.v. markers
      (Evan's Blue, or gadolinium-DTPA). Edema formation was evaluated with gravimetry,
      and T1-weighted MRI. In IAM, BBB opened immediately but closed rapidly, and
      remained closed for at least the next 36 hours whilst 24-hour hemispheric water
      content (HWC) rose by 0.9% (p < 0.01). In CCI, BBB opened in both hemispheres for
      up to 4 hours; four hour HWC in the uninjured hemisphere was indistinguishable
      from Sham, where HWC in the injured hemisphere rose by approximately 1.5% (p <
      0.005). We distinguished two THH animals based on Apparent Diffusion Coefficient
      (ADC) recovery: in ADC-recovery animals 4 hour cortical water content (CWC) was
      80.4 +/- 0.6%, cf 81.4 +/- 1.3% in ADC-non-recovery (p < 0.05). In all animals
      the BBB was open, however two populations of permeability were seen which likely
      related to flow-limited extravasation of gadolinium. In IAM edema forms despite
      only brief BBB opening. Although there is diffuse BBB opening with lateral
      contusion, edema only forms in the injured hemisphere. In THH, edema formation in
      the face of a widely permeable barrier is driven by ADC changes or cell swelling.
      Edema formation clearly does not correspond with BBB opening and an open BBB is
      clearly not required for edema formation. However we hypothesize that a permeable
      BBB permissively worsens the process, by acting as a low resistance pathway for
      ion and water movement. These findings are consistent with our general hypothesis
      that edema formation after TBI is mainly cytotoxic.

PMID- 11449991
TI  - Metabolic changes in pericontusional oedematous areas in mild head injury
      evaluated by 1H MRS.
AB  - In order to define metabolic brain changes associated with mild traumatic brain
      injury, proton magnetic resonance spectroscopy (MRS) was performed in patients
      with regional brain contusion and 13-15 of initial GCS score. The authors
      measured N-acetylaspartate(NAA)/creatine(Cr) ratio and lactate signal on in vivo
      proton MRS, which indicated cell loss and ischaemic dAmage respectively, in
      pericontusional oedematous areas (region of interest; ROI) adjacent to traumatic
      brain contusion on brain MRI to determine possible metabolic changes. The
      metabolic ratio of NAA/Cr and lactate/Cr peaks was measured both in the ROI and a
      corresponding region of the contralateral hemisphere (ROC) in seven patients and
      twenty-five normal control. In initial NAA/Cr ratios, the values of ROIs were
      significantly lower than those of the control (p = 0.009), but there was no
      difference either between ROI and ROC (p = 0.410) or between ROC of patients and
      the control (p = 0.199). In lactate/Cr ratios, the ROI in all seven patients and
      the ROC in two showed increased lactate signals. The lacate/Cr ratios of the ROIs
      were significantly elevated as compared to those of the ROCs (p = 0.02) and the
      control (p = 0.015). In 2-month follow up, lactate signals were absent or
      significantly reduced (p = 0.015). In no patients, clinical or radiological
      deterioration has been observed. Our results demonstrate that there is
      significant neuronal dysfunction in pericontusional oedematous areas as indicated
      by NAA/Cr ratios in the patients with mild head injury at both early and late
      stages. And there are significant ischaemic changes as indicated by increase of
      lactate level in ROI at early stage. These findings suggest that pericontusional
      oedematous areas can be vulnerable to secondary brain insults even in the
      patients with mild head injury.

PMID- 11449992
TI  - Endothelin-1 and nitric oxide affect human cerebromicrovascular endothelial
      responses and signal transduction.
AB  - Endothelium plays a central role in regulating the vascular tone, blood flow and
      blood brain barrier (BBB) permeability. The experiments presented here examine
      the mechanisms by which nitric oxide (NO) and endothelin-1 (ET-1) may be involved
      in these processes. The findings indicate that ET-1-stimulated [Ca2+]i
      accumulation occurs through activation of ETA receptor. The capacity of NO to
      affect this response was indicated by results showing: 1) a two-fold increase in
      ET-1-stimulated [Ca2+]i by L-NAME, the inhibitor of nitric oxide synthase, and 2)
      a dose-dependent decrease in [Ca2+]i accumulation by pretreatment with Nor-1 (NO
      donor). Abrogation of this Nor-1 effect by ODQ (an inhibitor of guanylyl cyclase)
      or Rp-8-pCPT-cGMPS (an inhibitor of protein kinase G) and inhibition of ET-1
      stimulated intracellular Ca2+ accumulation by 8-bromo-cGMP (a permeable, analog
      of cGMP) substantiate the involvement of interplay between ET-1 and NO in [Ca2+]i
      accumulation in HBMEC. ET-1 treatment also increased thickness of F-actin
      cytoskeletal filaments in HBMEC. This effect was attenuated by pretreatment with
      NO; NO also rarefied F-actin filaments in control cultures. The findings support
      a linkage between NO and ET-1 in regulating microvascular tone, microcirculation
      and BBB permeability and indicate a role for cGMP/cGMP protein kinase system and
      cytoskeletal changes in responses of HBMEC.

PMID- 11449993
TI  - LF16-0687 a novel non-peptide bradykinin B2 receptor antagonist reduces vasogenic
      brain edema from a focal lesion in rats.
AB  - Head injury world wide is still the most frequent cause of morbidity and
      mortality among the population under 45 years. Approximately 50% of patients
      dying from severe head injury have a therapy refractory intracranial pressure
      rise (Baethmann 1998). Traumatic brain edema, e.g. resulting from disruption of
      the blood-brain barrier is viewed as an important factor of the increased
      intracranial pressure. Bradykinin, an active peptide of the kallikrein-kinin
      system is considered to enhance brain edema formation which is attributed to its
      permeabilizing effect on the blood-brain barrier and on dilation of arterial
      blood vessels in the brain mediated by B2-receptors facilitating extravasation.
      Currently, LF16-0687, a novel non-peptide bradykinin B2 receptor antagonist was
      experimentally tested as to its therapeutical potential on vasogenic brain edema
      from a cortical focal lesion. Following trephination of the skull in anaesthesia,
      male Sprague-Dawley rats were subjected to a focal cold injury of the left
      parietal cortex. Animals of two experimental groups were receiving either LF16
      0687 as high or low dose, whereas one group of untreated animals with trauma was
      treated with 0.9% NaCl as continuous infusion beginning 10 min before until 24 h
      after lesion. 24 h after trauma the brain was removed from the skull, and the
      cerebral hemispheres were separated in the median plane for gravimetric
      assessment of hemispheric swelling. No significant reduction of hemispheric brain
      swelling (+7.4 +/- 2.9%) was found in animals receiving high-dose LF16-0687 as
      compared to the untreated controls. Brain swelling, however was significantly
      attenuated by the low-dose treatment, i.e. to +6.4 +/- 1.3%; vs. +9.3 +/- 1.1%
      found in the controls, (p < 0.05). The current data confirm that blocking of
      bradykinin B2-receptors by LF16-0687 is significantly attenuating vasogenic brain
      edema from a focal cold lesion. The therapeutical properties of the antagonist on
      brain edema formation cannot be attributed to a lowering of the blood pressure.
      Rather, specific blocking effects of B2-receptors in the brain appear to be
      involved. In conclusion, the understanding of secondary brain damage including
      brain edema in head injury has been markedly enhanced by the discovery of
      pathophysiologically active mediator compounds playing a role in its various
      manifestations. The current data confirm a pathophysiological function of
      bradykinin in vasogenic brain edema mediated by activation of B2-receptors.
      Currently it is studied whether LF16-0687 also reduces brain swelling when given
      after an insult.

PMID- 11449994
TI  - AT1 receptor antagonist prevents brain edema without lowering blood pressure.
AB  - In order to investigate the role of Angiotensin II (AII) for the vasogenic
      cerebral edema, the AT1 receptor antagonist (TCV-116) was administered to 19-week
      old stroke-prone spontaneously hypertensive rats (SHRSP) for 2 weeks at a dosage
      which did not decrease the blood pressure. Although no remarkable changes were
      found in blood pressure after treatment, the average brain weight of the treated
      group was relatively lower as compared to that of control SHRSP and no edematous
      changes were found in any brains. The immunohistochemical expression of
      intercellular adhesion molecule-1 (ICAM-1) was less and the glucose transporter-1
      (GLUT-1) expression was much more intense in the endothelial cells of the micro
      vessels in the cerebral cortex of the treated group. Fibrinogen expression around
      micro-vessels was also remarkably reduced in the treated group. A decreased
      expression of ICAM-1 in the treated group was confirmed by RT-PCR analysis. These
      results indicate that the AT1 receptor blockade ameliorates hypertensive cerebral
      injury in a blood pressure-independent manner and suggest that AII may have an
      important role for endothelial injury in severe hypertension.

PMID- 11449995
TI  - The effects of dopamine on edema formation in two models of traumatic brain
      injury.
AB  - The risk of vasopressors worsening cerebral edema has been raised. Previously we
      have reported that dopamine was able to restore cerebral blood flow in a model of
      monotonically rising intracranial pressure. In this study the effects of dopamine
      on cortical contusion and diffuse injury with secondary insult are examined.
      Adult male rats were divided into two groups: group 1 (n = 32)--Impact
      Acceleration Injury (IAM) with 30 minutes hypoxia and hypotension; group 2 (n =
      12)--controlled cortical impact (6.0 m/sec, 3 mm depth). Dopamine was
      administered 2 hours post-injury (10-60 micrograms/kg/min i.v.). Cerebral water
      content and apparent diffusion coefficients (ADC) values were measured at
      baseline and four hours post-injury using MRI. Preinjury water content was the
      same in each group. Group 1 was subdivided into Groups 1A & 1B based on the ADC
      profile. Post-injury water content in Group 1A did not differ between saline or
      dopamine treated animals. Water content was higher in Group 1B-dopamine (83.4 +/-
      1.1%) than Group 1B-saline animals (81.4 +/- 1.3%, p = 0.006). Contusion caused
      significant edema formation, however there was no significant difference between
      the dopamine treated or untreated group when considering either ipsilateral or
      contralateral cortex. Dopamine however significantly worsened edema in
      ipsilateral and contralateral hippocampus and both temporal cortices. ADC
      remained unchanged except in the contralateral hippocampus where both water
      content and ADC rose with dopamine suggesting precipitation of a vasogenic edema.
      In this study dopamine clearly worsened edema formation in two models of
      traumatic brain injury, and we conclude that there may be analogous clinical
      situations; therefore pressors should not be considered a 'blanket' therapy for
      all patients with a low cerebral perfusion pressure.

PMID- 11449996
TI  - A new antioxidant compound H-290/51 attenuates upregulation of constitutive
      isoform of heme oxygenase (HO-2) following trauma to the rat spinal cord.
AB  - Influence of a new antioxidant compound H-290/51 on carbon monoxide (CO)
      production following spinal cord injury was examined using immunohistochemistry
      of the constitutive isoform of heme oxygenase-2 (HO-2) in a rat model. Subjection
      of rats to 5 h spinal cord injury by making an incision into the right dorsal
      horn of the T10-11 segments resulted in upregulation of HO-2 in the injured and
      adjacent T9 and T12 segments. At this time, disruption of the blood-spinal cord
      barrier (BSCB) permeability, edema formation and cell injury were more
      pronounced. Pretreatment with H-290/51 (50 mg/kg, p.o., 30 min before trauma)
      significantly attenuated the HO-2 immunoreactivity along with breakdown of the
      BSCB permeability, edema and cell injury. These results for the first time
      demonstrate that the antioxidant compound H-290/51 is capable of attenuating HO-2
      expression and thereby influencing CO production. Furthermore, our observations
      indicate that oxidative stress is involved in CO production, as reflected by HO-2
      expression, which is injurious to the cord and H-290/51 exerts powerful
      neuroprotective effects in spinal cord injury.

PMID- 11449997
TI  - A bradykinin BK2 receptor antagonist HOE-140 attenuates blood-spinal cord barrier
      permeability following a focal trauma to the rat spinal cord. An experimental
      study using Evans blue, [131]I-sodium and lanthanum tracers.
AB  - The role of bradykinin in breakdown of the blood-spinal cord barrier (BSCB)
      permeability following a focal lesion to the cord was examined using a potent
      bradykinin BK2 receptor antagonist, HOE-140 in a rat model. Spinal cord injury
      was produced by an incision into the right dorsal horn of the T10-11 segment. In
      a separate group of rats HOE-140 (1 mg/kg) was administered intravenously 30 min
      before injury. A focal trauma to the cord markedly increased the extravasation of
      Evans blue and [131]I-sodium tracers in the cord at 5 h. Pretreatment with HOE
      140 significantly attenuated the extravasation of these tracers in the spinal
      cord. At ultrastructural level, lanthanum was seen within the endothelial cell
      cytoplasm, in vesicular profiles as well as in the basal lamina in the untreated
      traumatised rats. In HOE-140 treated rats, the lanthanum was mainly confined
      within the lumen. These observations strongly suggest that bradykinin is involved
      in the breakdown of the BSCB permeability probably via bradykinin BK2 receptors,
      not reported earlier.

PMID- 11449998
TI  - Combined therapy utilizing a novel Na+/H+ exchange inhibitor (SM-20220) and THAM
      for ischemic brain edema.
AB  - We investigated in the gerbil model whether the therapeutic effect of a novel
      Na+/H+ exchange inhibitor SM-20220 on ischemic brain edema could be enhanced by
      improving the decreased intracellular pH with an alkalizing agent, tris
      (hydroxymethyl) aminomethane (THAM). The left carotid artery of the animals was
      occluded twice for 10 min at a 5 hr interval. Ischemia-positive animals were
      selected and classified into the SM-20220- (0.5 mg/kg, i.p.) THAM- (2.0 ml/kg,
      i.v., 0.3M-THAM), combination of SM-20220 (0.5 mg/kg, i.p.) and THAM (2.0 ml/kg,
      i.v.), and vehicle- (0.9% saline, i.p.) treatment groups. Each agent was
      administered at 0, 6, 12 and 36 hr after recirculation following the 2nd episode
      of ischemia. The brain water, sodium and potassium contents were measured at 12,
      24, and 48 hr after recirculation. The water content of the ischemic hemisphere
      12 hr after recirculation was significantly lower in the combination-treated
      group (79.02%; P < 0.05) than in either the SM-20220- (79.28%) or THAM-treated
      group (79.32%). At 24 hr after recirculation the water content was significantly
      lower in the combination-treated group (79.83%, P < 0.05) than in the vehicle
      group (80.95%). At 48 hr after recirculation there were no significant
      differences in the water content between the vehicle group and any of the other
      treatment groups. The changes in brain water (delta H2O) and sodium plus
      potassium (delta Na + delta K) content in the ischemic hemisphere showed a
      significant correlation in each group. The combined treatment with the novel
      Na+/H+ exchange inhibitor SM-20220 and THAM is more effective on ischemic brain
      edema than treatment with a single agent. The results of this study indicate that
      improvement of intra- and extracellular acidosis by THAM infusion enhanced the
      activity of the NHE inhibitor SM-20220.

PMID- 11449999
TI  - Malignancy of brain tumors evaluated by proton magnetic resonance spectroscopy
      (1H-MRS) in vitro.
AB  - Biopsies of 6 malignant gliomas (grade 3 or 4) and 11 low-grade meningiomas were
      extracted with perchloric acid or methanol/water, and the fully-relaxed 1H-MRS
      spectra of the extracts containing water-soluble metabolites and a concentration
      and chemical shift standard were recorded at 11.4 T. The resonance signals
      assigned to inositol (Ino), glycerophospho- and phosphocholine (GPC + PC),
      choline (Cho), creatine and phosphocreatine (Cr + PCr), glutamate (Glu), acetate
      (Ac), alanine (Ala) and lactate (Lac) were integrated, and analyzed by two
      methods. First, the concentrations of the aforementioned substances in the
      bioptates were estimated from their resonance signals in the extracts. Second,
      these signals were normalized to the Cr + PCr resonance signal. The Mann-Whitney
      U-test was used to verify statistical significance between the data sets obtained
      for gliomas and meningiomas. When the first method of analysis was used, the only
      difference was in the Ala concentration, which in meningiomas was on average 4
      times higher than in gliomas (P < 0.01). However, when the second method of
      analysis was applied, gliomas expressed lower normalized resonance signals of Ala
      and Glu (P < 0.001, ranges not overlapping), Lac (P < 0.005), as well as Ino and
      GPC + PC (P < 0.05). In proton MR spectra of brain tumor tissue extracts
      containing water soluble metabolites, the resonance signals normalized to that of
      total creatine may provide a very good discrimination between malignant gliomas
      and low-grade meningiomas.

PMID- 11450000
TI  - Bradykinin 2 receptor antagonist LF 16-0687Ms reduces posttraumatic brain edema.
AB  - Activation of the kallikrein-kinin system contributes to traumatic brain edema
      formation. Inhibition of bradykinin 2 (B2) receptors has been shown to
      successfully reduce brain edema formation. The purpose of this study was to
      investigate the protective effect of the novel nonpeptide B2 receptor antagonist
      LF 16-0687Ms in brain-injured rats. Contusion was produced in forty rats by
      controlled cortical impact injury. Five minutes after trauma rats received a
      single dose of 0, 3, or 30 mg/kg of LF 16-0687Ms. After 24 hours brain swelling
      and hemispheric water content were determined. Brain swelling was significantly
      decreased by 25% in the low and 27% in the high dose group compared to controls
      (p < 0.03). Water content of the traumatized hemisphere tended to be decreased
      (80.2 +/- 0.1 vs. 80.4 +/- 0.1%) while water content of the non-traumatized
      hemispheres tended to be increased after administering LF 16.0687Ms (79.3 +/- 0.1
      vs. 79.0 +/- 0.1%). Single administration of the novel nonpeptide B2 receptor
      antagonist LF 16-0687Ms significantly reduces brain swelling. The missing
      significant reduction in water content of the traumatized hemisphere, however,
      could be related to an unspecific increase in water content due to LF 16.0687Ms
      as suggested by increased water content in the non-traumatized hemisphere.

PMID- 11450001
TI  - Influence of alcohol exposure on S-100b serum levels.
AB  - Recent assessment of the glia cell-derived neuroprotein S-100b in serum has been
      considered as a screening method for possibly occult brain injury in patients
      with minor head trauma (MHT). Since MHT is associated with alcohol intoxication
      in up to 50% of patients requiring emergency treatment, the blood-brain barrier
      (BBB) as well as neuronal cell integrity may be also affected by alcohol abuse.
      So far, however, no valid data are available on the release of S-100b after
      alcohol exposure. Thus, the aim of our study was to investigate S-100b serum
      levels in a controlled alcohol exposure paradigm. 22 healthy volunteers were
      included in the study, blood samples were drawn prior to and about 90 minutes
      after drinking. The amount of alcohol was adjusted to the body weight. A mean of
      66.7 +/- 14.81 g was consumed giving raise to a blood alcohol concentration of
      0.827 +/- 0.158@1000. S-100b serum levels assayed by a luminescence immunoassay
      were compared with those of MHT patients. The still preliminary results suggest
      no increase of the serum S-100b levels (0.0509 +/- 0.048 ng/ml versus 0.0422 +/-
      0.044 ng/ml) after moderate alcohol consumption. In contrast, MHT patients with
      alcohol intoxication (1.6 +/- 0.77@1000) revealed a significant up to 10fold
      elevation of S-100b serum levels. Because of the much higher blood alcohol
      concentration in the MHT patients compared to the control collective, a potential
      relationship between excessive alcohol consumption and the release of S-100b in
      minor head trauma can still not be excluded. Further investigations on this topic
      are in progress.

PMID- 11450002
TI  - Laser Doppler scanning: how many measurements are required to assess regional
      cerebral blood flow?
AB  - This study was initiated to determine the optimal number of measuring sites
      necessary to estimate regional cerebral blood flow (CBF) under pathophysiological
      conditions. 25 rats were exposed to 15 minutes of global cerebral ischemia. Local
      CBF was sequentially measured by laser Doppler (LD) at 32 locations during
      baseline conditions, ischemia and reperfusion using a computer-controlled
      scanning technique. A simulation study was performed based on 800 local
      measurements at each time point: random samples (size 1-100) were repeatedly
      drawn to estimate the variability of median flow. Accuracy was defined as
      probability that the simulated median differed less than +/- 5 LD-units from the
      true median of the 800 data. Above a single location, CBF was measured with an
      accuracy of 21.6 +/- 0.4% (baseline conditions, n = 100 simulations, mean +/-
      SEM), 85.8 +/- 0.4% (ischemia) and 11.1 +/- 0.3% (30th min. reperfusion).
      Accuracy increases to 75.2 +/- 0.5% (baseline conditions), 100 +/- 0% (ischemia)
      and 41.8 +/- 0.6% (30th min. reperfusion) if 24 locations are scanned. Scanning,
      therefore, improves accuracy and reduces variability of CBF measurements. With
      enough local CBF measurements laser Doppler assessment of regional CBF is
      possible. Single location CBF assessment is sufficiently accurate only during
      ischemia. During reperfusion, when accuracy is half reduced compared to baseline
      conditions, larger sample sizes are required.

PMID- 11450003
TI  - Assessment of 2-chloroadenosine treatment after experimental traumatic brain
      injury in the rat using arterial spin-labeled MRI: a preliminary report.
AB  - Adenosine is a putative endogenous neuroprotectant. Its action at A1 receptors
      mitigates excitotoxicity while action at A2 receptors increases cerebral blood
      flow (CBF). We hypothesized that cerebral injection of the adenosine analog, 2
      chloroadenosine, would decrease swelling and increase CBF early after
      experimental traumatic brain injury (TBI). To test this hypothesis, rats were
      anesthetized and subjected to TBI using a controlled cortical impact (CCI) model
      (n = 5/group). Immediately after injury, 2-chloroadenosine (0.3 nmole in 2
      microliters) or an equal volume of vehicle were stereotactically injected lateral
      to the area of contusion. Using magnetic resonance imaging (MRI), in vivo spin
      lattice relaxation time of tissue water (Tlobs) and CBF (arterial spin labeling)
      were measured in a 2-mm thick slice in the injured and non-injured hemispheres at
      3-4 h after CCI. In a separate, preliminary experiment, the effect of 2
      chloroadenosine injection in normal rat brain was studied. Rats (n = 2) were
      anesthetized and a burr hole was made for injection of 2-chloroadenosine into the
      same site as in the TBI model. One rat received the standard dose of 0.3 nmole
      and one rat received a 6 nmole injection. Tlobs and CBF studies were obtained 1.5
      3.5 h after injection, using the same MRI methods as in the TBI study. In rats
      subjected to TBI, treatment with 2-chloroadenosine attenuated the increase in
      Tlobs after injury (p < 0.05 for treatment vs vehicle) in both hippocampus and
      cortex ipsilateral to injury. However, treatment with 2-chloroadenosine did not
      improve post-traumatic hypoperfusion. In normal rats, injection of 0.3 nmole of 2
      chloroadenosine did not increase CBF, but the higher dosage of 6 nmole
      dramatically increased hemispheric CBF by 1.5-2.0-fold. The effect of local
      injection of 2-chloroadenosine at a dose of 0.3 nmole after experimental TBI on
      Tlobs presumably represents a reduction in post-traumatic edema. This reduction
      in edema, along with the augmentation of CBF seen in normal rats at higher dosage
      (6 nmole), supports a role for adenosine in neuroprotection following TBI.

PMID- 11450004
TI  - Time course of trace of diffusion tensor [Trace(D)] and histology in brain edema.
AB  - We examined the correlation between changes in the trace of diffusion tensor
      [Trace(D)], regional water content and tissue ultrastructure relating to cellular
      (cytotoxic) and vasogenic brain edema. Cellular edema was induced by left middle
      cerebral artery occlusion in cats (Kuroiwa T et al., 1998). Vasogenic edema was
      induced in the white matter of cats by a cold lesion (Kuroiwa T et al., 1999). In
      cellular edema, the water content increase correlated linearly with the Trace(D)
      decrease in both the gray and white matter. However, both the slopes and
      intercepts of the correlation lines were significantly different. Hydropic
      astrocytic swelling was seen in both structures, and in the white matter,
      oligodendrocytic and myelinated axonal swelling were observed. In vasogenic
      edema, the increase in Trace(D) showed a significant linear correlation with the
      increase in tissue water content. Histologically, nerve fibers were dissociated
      and the extracellular space was markedly enlarged with protein-rich fluid. These
      result showed that the different slopes and intercepts of the water content-
      Trace(D) correlation lines for different subtype of brain edema, which reflect
      different ultrastructural localization of water, should be taken into account
      when evaluating brain edema using Trace(D) mapping.

PMID- 11450005
TI  - L-histidine but not D-histidine attenuates brain edema following cryogenic injury
      in rats.
AB  - Oxygen free radicals have been implicated in the genesis of traumatic brain
      injury and brain edema (BE). Recent studies have suggested that hydroxyl radical
      can initiate lipid peroxidation, thus producing lipid-free radicals that may
      become important sources of singlet oxygen. L-histidine, a singlet oxygen
      scavenger, potentially can be used to treat BE. In this study we investigated the
      effects of L-histidine and D-histidine on BE following cryogenic injury in rats.
      Male Wistar rats were anaesthetized with chloral hydrate. Vasogenic BE was
      produced by a cortical freezing lesion. Generation of singlet oxygen from
      photoactivation of rose bengal was studied by electron spin resonance (ESR).
      Animals were separated into four groups: sham rats (n = 5), saline-treated rats
      (n = 10), L-histidine treated rats (n = 6) and D-histidine treated rats (n = 7).
      Each agent (100 mg/kg) was administered intravenously at 30 minutes before lesion
      production. Animals were sacrificed at 24 hours after lesion production and the
      brain water content was determined by the dry-wet weight method. L-histidine had
      no effect on rectal and brain temperature. Election Spin Resonance studies
      demonstrated that L-histidine is a singlet oxygen scavenger. L-histidine but not
      D-histidine significantly attenuated BE following cryogenic injury (p < 0.05). In
      conclusion, L-histidine is useful in the treatment of traumatic BE.

PMID- 11450006
TI  - Oxygen delivery and oxygen tension in cerebral tissue during global cerebral
      ischaemia: a swine model.
AB  - Interest in tissue oxygen (PtiO2) monitoring is increasing. However the exact
      interactions between ptiO2, systemic and cerebral variables are a matter of
      debate. Particularly, the relationship between ptiO2, cerebral oxygen supply and
      consumption needs to be clarified. We designed a model to achieve progressive
      Cerebral Blood Flow (CBF) reduction through 3 steps: 1. baseline, 2. CBF between
      50-60% of the baseline, 3. CBF < 30% of the baseline. In 7 pigs, under general
      anaesthesia, Cerebral Perfusion Pressure (CPP) and CBF were reduced through the
      infusion of saline in a lateral ventricle. PtiO2 and CBF were monitored
      respectively through a Clark electrode (Licox, GMS) and laser doppler (Peri
      Flux). Blood from superior sagittal sinus and from an arterial line was
      simultaneously drawn to calculate the artero-venous difference of oxygen (AVDO2).
      Brain oxygen supply was calculated by multiplying relative CBF change and
      arterial oxygen content. PtiO2 reflected CBF reductions, as it was 27.95 (+/-
      10.15) mmHg during the first stage of intact CBF, declined to 14.77 (+/- 3.58)
      mmHg during the first CBF reduction, declined to 3.45 (+/- 2.89) mmHg during the
      second CBF reduction and finally fell to 0 mmHg when CBF was completely
      abolished. CBF changes were also followed by a decline in O2 supply and a
      parallel increase in AVDO2. CONCLUSION: This model allows stable and reproducible
      steps of progressive CBF reduction in which ptiO2 changes can be studied together
      with oxygen supply and consumption.

PMID- 11450007
TI  - ICP and MABP following traumatic subarachnoid hemorrhage in the rat.
AB  - Traumatic subarachnoidal hemorrhage (t-SAH) is a common finding in head-injured
      patients occurring with a frequency of 39% according to data of the Traumatic
      Coma Data Bank. The present study is the first description of a t-SAH-model with
      particular emphasis on patterns of intracranial pressure (ICP) changes and mean
      arterial blood pressure (MABP) response. Diffuse brain injury was produced in
      intubated and ventilated adult Sprague-Dawley rats (N = 24) using a brass weight
      (500 gm) free falling from a predetermined height (1.5 m) on a steel disc glued
      to the skull of the rat. Before induction of the injury, heparin was administered
      intra-arterially (i.a.) and antagonised after injury by protamine. MABP
      recordings and ICP-recordings were performed continuously. Histopathology was
      undertaken. Following injury MABP decreased from 138 +/- 14 mmHg to 89 +/- 22
      mmHg. During 5 to 15 min ICP increased up to 89.4 +/- 50.4 mmHg, decreasing
      slowly within 60 min in surviving animals. The mortality rate was 41.6%. All
      brains showed a severe subarachnoid hemorrhage in the basal cisterns and cell
      loss within the brainstem. Experimental t-SAH is possible. Following t-SAH there
      is a subacute increase of ICP due to the actual bleeding. The model may provide
      deeper understanding in the basic physiological patterns of t-SAH.

PMID- 11450008
TI  - Real time monitoring of glutamate following fluid percussion brain injury with
      hypoxia in the rat.
AB  - In this study, extracellular glutamate (Glu) was monitored in real time using a
      biosensor following traumatic brain injury (TBI) either with or without inducing
      hypoxia in the rat Fluid-percussion model. We also measured the cortical
      contusion volume at 3 days after the insult. The animals were divided into 3
      groups. Group 1 was subjected to TBI only, Group 2 to TBI followed by 20 min of
      moderate hypoxia (FiO2: 10%) and Group 3 to 20 min of moderate hypoxia without
      TBI. The surge increase in the extracellular Glu concentration occurred
      immediately after TBI in Groups 1 and 2. Group 2 showed a prolonged efflux of Glu
      during hypoxia. Group 3 Glu showed low continuous steady levels. The contusion
      volume in Group 2 was significantly larger than in Group 1. To test the possible
      involvement of apoptosis in Groups 1 and 2, rats were sacrificed at 1, 6, 24 and
      72 h after TBI. Immunohistochemical studies showed an increased number of both
      CPP32 positive cells at 24 h and TUNEL cells at 72 h in Group 2. These results
      suggest that TBI with moderate hypoxia induced a prolonged efflux of Glu that
      resulted more cortical damage due to necrosis and apoptosis.

PMID- 11450009
TI  - rCBF in hemorrhagic, non-hemorrhagic and mixed contusions after severe head
      injury and its effect on perilesional cerebral blood flow.
AB  - Intracerebral contusions can lead to regional ischemia caused by extensive
      release of excitotoxic aminoacids leading to increased cytotoxic brain edema and
      raised intracranial pressure. rCBF measurements might provide further information
      about the risk of ischemia within and around contusions. Therefore, the aim of
      the presented study was to compare the intra- and perilesional rCBF of
      hemorrhagic, non-hemorrhagic and mixed intracerebral contusions. In 44 patients,
      60 stable Xenon-enhanced CT CBF-studies were performed (EtCO2 30 +/- 4 mmHg SD),
      initially 29 hours (39 studies) and subsequent 95 hours after injury (21
      studies). All lesions were classified according to localization and lesion type
      using CT/MRI scans. The rCBF was calculated within and 1-cm adjacent to each
      lesion in CT-isodens brain. The rCBF within all contusions (n = 100) of 29 +/- 11
      ml/100 g/min was significantly lower (p < 0.0001, Mann-Whitney U) compared to
      perilesional rCBF of 44 +/- 12 ml/100 g/min and intra/perilesional correlation
      was 0.4 (p < 0.0005). Hemorrhagic contusions showed an intra/perilesional rCBF of
      31 +/- 11/44 +/- 13 ml/100 g/min (p < 0.005), non-hemorrhagic contusions 35 +/-
      13/46 +/- 10 ml/100 g/min (p < 0.01). rCBF in mixed contusions (25 +/- 9/44 +/-
      12 ml/100 g/min, p < 0.0001) was significantly lower compared to hemorrhagic and
      non-hemorrhagic contusions (p < 0.02). Intracontusional rCBF is significantly
      reduced to 29 +/- 11 ml/100 g/min but reduced below ischemic levels of 18 ml/100
      g/min in only 16% of all contusions. Perilesional CBF in CT normal appearing
      brain closed to contusions is not critically reduced. Further differentiation of
      contusions demonstrates significantly lower rCBF in mixed contusions (defined by
      both hyper- and hypodense areas in the CT-scan) compared to hemorrhagic and non
      hemorrhagic contusions. Mixed contusions may evolve from hemorrhagic contusions
      with secondary increased perilesional cytotoxic brain edema leading to reduced
      cerebral blood flow and altered brain metabolism. Therefore, the treatment of ICP
      might be individually modified by the measurement of intra- and pericontusional
      cerebral blood.

PMID- 11450010
TI  - The synergistic effect of acute subdural hematoma combined with diffuse traumatic
      brain injury on brain edema.
AB  - It is well-documented that acute subdural hematoma (ASDH) following diffuse
      traumatic brain injury (dTBI) contributes to severe disability and high
      mortality. The objective of this study was to characterize edema formation in a
      model of ASDH and ASDH following dTBI. Eighteen Sprague-Dawley rats were
      separated into three groups: Sham operated (n = 6), ASDH (n = 6), ASDH following
      dTBI (n = 6). Diffuse TBI was produced via the Impact-Acceleration Model [10].
      ASDH was induced in the left hemisphere using the well-described method [11].
      Total tissue water content was determined 4 hours after TBI utilizing wet
      weight/dry-weight assessment. Our results show that ASDH causes a significant
      increase in tissue water content in the left hemisphere (79.2 +/- 0.7%) compared
      with the contralateral hemisphere (78.5 +/- 0.5%, p = 0.009). Animals exposed to
      ASDH following dTBI had significantly greater edema formation than those with
      ASDH (right: 80.9 +/- 0.4%, left: 80.5 +/- 0.7, p = 0.008). There was no
      significant difference between the left and right hemisphere. We conclude that
      edema formation in ASDH is worsened by the combination of dTBI and ASDH.
      Furthermore a diffuse and focal injury in combination retain the features of the
      diffuse injury, but with increased severity. Further studies are required to
      elucidate the synergistic mechanisms involved in these pathological processes.

PMID- 11450011
TI  - Mitogen-activated protein kinase plays an important role in hemolysate-induced
      contraction in rabbit basilar artery.
AB  - OBJECT: Mitogen-activated protein kinase (MAPK) is an important signaling factor
      in the vascular proliferation and contraction, the two features of cerebral
      vasospasm following subarachnoid hemorrhage. We studied the possible involvement
      of MAPK in hemolysate-induced signal transduction and contraction in rabbit
      basilar artery. METHODS: Isometric tension was used to record the contractile
      response of rabbit basilar artery to hemolysate. Western blots using antibodies
      for MAPK were conducted. 1) Hemolysate produced a concentration-dependent
      contraction of rabbit basilar artery. Pre-incubation of arteries with MAPK kinase
      inhibitor PD-98059 markedly reduced the contraction induced by hemolysate. PD
      98059 also relaxed, in a concentration-dependent fashion, the sustained
      contraction induced by hemolysate (10%). 2) Hemolysate produced a time-dependent
      elevation of MAPK immunoreactivity in Western blot in rabbit basilar artery. MAPK
      was enhanced 3 min after hemolysate exposure and the effect reached maximum at 5
      min. The immunoreactivity of MAPK decayed slowly with time, but the level of MAPK
      was still higher than the basal level even at two hours after exposure to
      hemolysate. 3) Pre-incubation of arteries with MAPK kinase inhibitor PD-98059
      abolished the effect of hemolysate on MAPK immunoreactivity. CONCLUSION:
      Hemolysate produced contraction of rabbit basilar artery possibly by activation
      of MAPK. MAPK inhibitors may be useful in the treatment of cerebral vasospasm.

PMID- 11450012
TI  - Morphological presentation of posttraumatic vasospasm.
AB  - Posttraumatic vasospasm is a well-recognized sequela of head injury. The risk
      factors associated with posttraumatic vasospasm have not been well defined. We
      studied 119 consecutive patients with head injury to determine the risk factors
      for posttraumatic vasospasm. Posttraumatic vasospasm was detected in 32 (35.6%)
      of 90 patients. Among these patients, 29 (90.6%) had severe head injury and 3
      (9.4%) had moderate head injury. None of the patients with mild head injury
      suffered posttraumatic vasospasm. In most cases, the onset of posttraumatic
      vasospasm began on the fifth day and lasted 1 to 9 days. In 8 (25%) patients,
      posttraumatic vasospasm began within the first three days of the head injury.
      Clinical deterioration was documented in two (2.5%) patients. Morphologically,
      posttraumatic vasospasm resembled features of aneurysmal vasospasm. We found
      increased corrugation of the internal elastic lamina and increased amounts of
      connective tissue in the subendothelial layer. These findings showed that
      posttraumatic vasospasm, although clinically more mild, demonstrated the same
      morphological changes as did aneurysmal vasospasm.

PMID- 11450013
TI  - Role of tyrosine kinase in fibroblast compaction and cerebral vasospasm.
AB  - Hemolysate, a proposed causative agent for cerebral vasospasm following
      subarachnoid hemorrhage, produces contraction of cerebral arteries by activation
      of tyrosine kinases. In addition, hemolysate accelerates fibroblast collagen
      compaction that could play a role in cerebral vasospasm. We studied the effect of
      hemolysate on tyrosine phosphorylation and fibroblast collagen compaction in
      cultured dog cerebral and human dermal fibroblasts using tyrosine kinase
      inhibitors and tyrosine antibodies (Western blot). 1) Hemolysate was found to
      enhance tyrosine phosphorylation of two proteins approximately 64 and 120 kDa.
      The effect of hemolysate was time- and concentration-dependent. 2) Two main
      components in hemolysate, oxyhemoglobin and adenosine triphosphate (ATP),
      produced similar results to that of hemolysate. 3) Tyrosine kinase inhibitor
      genistein and tyrphostin A51 (30 microM) markedly reduced the effect of
      hemolysate on tyrosine phosphorylation. 4) In another study, hemolysate increased
      fibroblast collagen compaction and the effect of hemolysate was reduced by
      genistein and tyrphostin A51. We conclude that hemolysate activates tyrosine
      kinase that may lead to acceleration of fibroblast compaction. This effect of
      hemolysate may contribute to cerebral vasospasm.

PMID- 11450014
TI  - Toxin-induced vasogenic cerebral oedema in a rat model.
AB  - Vasogenic cerebral oedema (VCO) was induced in Hooded Wistar rats by
      intraperitoneal injection of Clostridium perfringens type D epsilon prototoxin.
      Animals were killed, 1 h to 14 d postinjection, by perfusion fixation under
      general anaesthesia. VCO was detected by the presence of endogenous albumin in
      the brain, visualised by immunocytochemistry. As early as 1 h postinjection,
      albumin was detected in the walls of cerebral microvessels. Maximal diffuse
      leakage within the neural parenchyma was seen at 24 and 48 h and immunoreactivity
      was still present at 4 d. At 7 d only few foci were seen, and at 14 d albumin
      distribution was similar to that in controls. Ultrastructural assessment of the
      microvessels showed swelling of many astrocytic processes and abnormalities of
      the endothelial cells varying from swelling with loss of cytoplasmic organelles
      to cells showing increased electron density. Immunostaining for the endothelial
      barrier antigen (EBA) showed strongly immunoreactive vessels throughout normal
      brains. Experimental animals showed partial reduction in EBA expression, most
      evident at 24 and 48 h, with gradual recovery to normal by 14 d. The exact role
      that EBA plays in the intact BBB remains obscure.

PMID- 11450015
TI  - Expression of water channel mRNA following cerebral ischemia.
AB  - Water channel is a protein which regulates transcellular water permeability.
      Among mRNA expression of six principal mammalian water channels, AQ4 mRNA
      expression was highest in the brain. Water channels are supposed to regulate
      cerebral edema but the detailed physiological and pathological function is
      unknown. Brain edema has been analyzed as an aspect of ion channel injury or
      membrane injury. However the transportation of water molecule itself following
      cerebral ischemia is unknown. As water channels transport only water molecules,
      the functional changes of water channels following cerebral ischemia are of great
      interest. To evaluate the role of water channels in cerebral edema following
      cerebral ischemia, the changes of water channel mRNA expression were evaluated.
      Cerebral edema was induced by suture method. The extraction of water channel mRNA
      was performed according to Chomczynsli and Sacchi. RT-PCR was applied to
      extracted mRNA. Water channel mRNA electrophoresis was performed. For semi
      quantified evaluation of water channel, mRNA intensities of the infarct
      hemisphere and normal hemisphere were compared. The expression of water channel
      mRNA was decreased following cerebral ischemia. This damage leads to loose
      physiological control of water permeability of the cell membrane in the neuron,
      glia and endothelial cells which leads to brain edema.

PMID- 11450016
TI  - Brain oxygen tension during hyperoxia in a swine model of cerebral ischaemia.
AB  - Arterial hyperoxia improves oxygen tension measured into the cerebral tissue
      (ptiO2). The extent of this improvement in ameliorating O2 delivery to the
      cerebral tissue, when cerebral blood flow (CBF) is reduced, is still unclear. The
      present experiment was developed to investigate the effect of arterial hyperoxia
      at normal or reduced CBF (baseline, CBF = 50-60%, and CBF = 20-30% of the
      baseline). CBF reduction was achieved in 7 pigs by saline infusion in a lateral
      ventricle. PtiO2 was measured by Licox equipment. Arterovenous oxygen difference
      (AVDO2) was calculated as the difference between arterial oxygen content and
      superior sagittal sinus oxygen content. Hyperoxia was induced by increasing
      inspired oxygen fraction to 100%. PtiO2 moved respectively from 27.95 (+/- 10.15)
      to 45.98 (+/- 15.31), from 14.77 (+/- 3.58) to 30.71 (+/- 12.2), and from 3.45
      (+/- 2.89) to 11.1 (+/- 12.6) mmHg at normal CBF, after the first reduction and
      after the second reduction. O2 supply showed only a negligible increase. AVDO2
      decreased during the phases of intact and moderate CBF impairment, while it did
      not change during the phase of severe CBF impairment. IN CONCLUSION: an increase
      of ptiO2 does not necessarily correspond to an improvement of brain oxygen
      delivery. The small increase in oxygen delivery due to hyperoxia may cause a
      slight improvement in the balance between O2 delivery and consumption during mild
      CBF reduction, but such improvement is negligible when severe CBF reduction
      occurs.

PMID- 11450017
TI  - The synergistic effect of high K+ and hypoxia on extracellular concentrations of
      neuroactive amino acid in hippocampus.
AB  - In the present study, we examined extracellular concentrations of glutamate (Glu)
      in hypoxia using ringer solution with a high potassium (K+) level using
      microdialysis. Based on our findings, we hypothesized that the concentration of
      extracellular K+ caused a greater efflux of Glu. We used male SD rats and
      separated them into 3 groups based on the K+ concentration of Ringer solution
      (RS), consisting of normal (4 mM), 40 mM and 150 mM groups. We stereotactically
      inserted the microdialysis probe into the hippocampus, and perfused the RS for 60
      min before imposing hypoxia. Subsequently, while perfusing RS, hypoxia (7% O2 +
      93% N2 gas) was induced in all 3 groups for 20 min. In the normal and 40 mM of K+
      concentration groups, the Glu level did not increase, but in the 150 mM of K+
      concentration group, the Glu level increased while being perfused with RS and a
      larger increase in Glu was observed after inducing hypoxia. This result suggests
      that the extracellular concentration of K+ plays a role in the mechanism of
      increased neuronal vulnerability caused by hypoxia after TBI.

PMID- 11450018
TI  - Spreading depression induces permanent cell swelling under penumbra conditions.
AB  - BACKGROUND: Spreading depression (SD) is known to go along with temporary
      breakdown of ion gradients and cell swelling which spontaneously normalizes.
      Here, the effects of SD at reduced flow conditions as encountered in the ischemic
      penumbra are examined. METHODS: In rats the right carotid artery was permanently
      occluded. MABP was lowered to 50 mmHg for 30 min. This is sufficient to reduce
      CBF to penumbra-like conditions in the right hemisphere. The following parameters
      were assessed: rCBF, DC potential, and tissue impedance. 5 or 15 min after onset
      of flow reduction one SD wave was initiated by microinjection of KCl. Histology
      was performed after 7 days. RESULTS: In animals with hypotension there was
      depolarization resembling anoxic depolarization after SD induction and an
      uncoupling of CBF and metabolism only in the right hemisphere. Impedance
      increased with SD but did not recover spontaneously as long as rCBF remained
      reduced. 15 min of SD-induced cell swelling was tolerated without permanent
      damage, whereas 25 min were followed by severe neuron loss in the affected cortex
      after 7 days. CONCLUSIONS: The study demonstrates the induction of penumbra
      conditions in the cortex of one hemisphere. SD is followed by cell swelling which
      persists as long as flow is critically reduced. The experiments illustrate how
      peri-infarct depolarizations may detrimentally affect the penumbra.

PMID- 11450019
TI  - Cerebral blood flow and the secondary growth of brain tissue necrosis after
      trauma.
AB  - A local brain tissue necrosis from trauma progresses during the following 24
      hours or longer. A decrease in cerebral blood flow has been observed both in the
      necrotic as well as adjacent cortical region, which may influence expansion of
      the lesion into the perifocal brain tissue. Currently the regional cortical blood
      flow (rCBF) was assessed by using scanning laser Doppler fluxmetry. Brain tissue
      necrosis was induced by a highly standardised cold lesion. We attempted to
      inhibit the development of posttraumatic ischemia in and around the focal lesion
      by infusion of a hypertonic/hyperoncotic saline/starch solution. The infusion
      therapy resulted in a temporary improvement of posttraumatic blood flow in both
      necrotic and distant cortical regions. However, the expansion of the focal
      necrosis was not reduced. Additional investigations are in progress to determine
      whether further amelioration with a longer duration of rCBF increase is effective
      in combination with methods of neuroprotection to inhibit the secondary lesion
      growth after a traumatic insult.

PMID- 11450020
TI  - The role of proteolytic enzymes in focal ischaemic brain damage.
AB  - Although various neuroprotective and fibrinolytic drugs are currently under
      evaluation in the acute stages of ischaemic stroke, their therapeutic potential
      is likely to be limited by unwanted side effects and a narrow time window of
      opportunity for intervention. Proteolytic enzymes are involved in the catabolism
      of peptide neurotransmitters and structural cellular proteins in normal brain and
      have been implicated in the pathogenesis of neurodegenerative disorders. We
      hypothesised that activation of these enzymes might also play a crucial role in
      effecting ischaemic neuronal injury, thereby providing a potential site for
      therapeutic intervention in human stroke. Focal cerebral ischaemia was induced by
      thermocoagulation of the left middle cerebral artery in aged (30 month) male
      Wistar rats who were pre-treated with saline or the competitive N-methyl-D
      Aspartate antagonist D-CPP-ene, which has been shown to be neuroprotective in
      young animal models of stroke. Major protease activities were analysed in the
      left (ischaemic) and right (non-ischaemic) hemispheres, following tissue
      homogenisation. Data have been analysed using Mann-Whitney tests and are
      presented as means +/- standard errors. Enzyme activity decreased in ischaemic
      brain; for example, the mean activity of dipeptidyl aminopeptidase I was 23 +/- 3
      and 43 +/- 6 nmol substrate/hour/ml brain extract in the left and right
      hemispheres respectively (n = 10, p < 0.05). Ischaemic neuronal injury is not
      effected by the early activation of proteolytic enzymes and protease inhibitors
      are therefore unlikely to be of benefit in human stroke.

PMID- 11450021
TI  - Effect of intracerebral lesions detected in early MRI on outcome after acute
      brain injury.
AB  - In the present study we classified intracerebral lesions likely to influence the
      outcome of head injured patients according to localization, lesion type, lesion
      number and lesion volume. A score of intracerebral lesions based on findings in
      early MRI is presented. Early MRI studies were performed in 30 patients (average
      5-6 days after trauma) and outcome (GOS) was determined after 3 and 12 months.
      Lesions were classified and lesion volume V was calculated (V = pi abc/6). The
      applied intracerebral lesion score included lesions in the frontal cortex, basal
      ganglia, corpus callosum and brainstem. Patients in a persistent vegetative state
      (PVS) showed a higher number (p = 0.018) and volume (p = 0.013) of frontal
      lesions as compared to the non-vegetative group (NPVS). Lesion volume in basal
      ganglia differed significantly between PVS and NPVS (p = 0.01) and correlated to
      outcome (r = -0.65, p < 0.005). Volume difference in the corpus callosum between
      PVS and NPVS was significant (p = 0.02). The number (r = -0.61, p < 0.005) and
      volume (r = -0.62, p < 0.005) of brainstem lesions correlated to outcome and PVS
      differed in number (p = 0.012) and volume (p = 0.006). The intracerebral lesion
      score correlated to the GOS (r = -0.57, p = 0.001) and PVS and NPVS differed
      significantly. A lesion volume exceeding 40 ml in the frontal cortex, 3.5 ml in
      the basal ganglia, 4 ml in the corpus callosum or 1.5 ml in the brainstem is
      likely to lead to an unfavorable outcome. More than 4 lesions in the frontal
      cortex or 3 lesions in the brainstem appeared more frequent in patients with
      unfavorable outcome. Treatment strategies in the early phase after brain injury
      could be modified by the knowledge of certain lesions only visible on MRI.

PMID- 11450022
TI  - Effects of brain oedema in the measurement of ischaemic brain damage in focal
      cerebral infarction.
AB  - In a model of focal cerebral ischaemia, enlargement of ischaemic tissue by
      ischaemic brain oedema is one of the major problems in the measurement of
      infarction volume. To minimize an error of this overestimation, several methods
      have been proposed. However, there has been no attempt to compare these methods
      to elucidate their eligibility in the measurement of ischaemic area. The authors
      used three different morphometric analyses in the measurement of infarction
      volume to assess the antiischaemic affects of a competitive NMDA antagonist, D
      CPPene in MCA occlusion model of the rat: a direct measurement, the Swanson's
      method, and a measurement using a diagram. Post-occlusion treatment of D-CPPene
      (4.5 mg/kg, i.v. +3 mg/kg/h, i.v.) produced reduction of infarction volume to
      about 40% compared to the control (P < 0.05). The volume of infarction determined
      by the direct measurement was much larger than that by Swanson's or diagram
      method (P < 0.05), about 70% larger in the control and by two times in the
      treated. However, there was no significant difference in the measured volume
      between the Swanson's and diagram methods. The protection rate, which was
      calculated as % = (infarct volume of the control--that of the treated/infarct
      volume of the control) x 100%, was larger in the Swanson's and diagram methods
      than in the direct measurement. In conclusion, it is confirmed that the direct
      measurement at the peak time of ischaemic brain oedema brings about not only an
      overestimation of infarction volume but lower protection rate also, compared to
      the methods designed to minimize the overestimation. Our results also demonstrate
      the diagram method is useful in reducing overestimation of infarct volume that
      may be caused by ischaemic brain oedema, though this method was not designed for
      the purpose of avoiding oedema at first.

PMID- 11450023
TI  - Characterizing edema associated with cortical contusion and secondary insult
      using magnetic resonance spectroscopy.
AB  - It is traditionally believed that edema associated with brain contusion is
      vasogenic. The objective of this study was to quantify and characterize the edema
      in cortical contusion coupled with early hypoxia and hypotension. Sprague-Dawley
      rats were randomised into six groups: Sham, Trauma moderate (Tm), Trauma severe
      (Ts), Hypoxia and Hypotension (HH), Tm and Ts with HH (THHm; THHs). Trauma was
      induced with controlled cortical impact; associated secondary insults lasted 30
      minutes. Water content was measured using tissue longitudinal relaxation time
      (T1). Apparent diffusion coefficient of water (ADC) was calculated from diffusion
      weighted imaging and single voxel spectroscopy. In the trauma groups ICP
      increased at 30 minutes post trauma (p < 0.05) and then gradually decreased. Only
      in the THH groups, ICP showed a trend to continually rise. No ICP variations were
      seen in the others groups. The increase in water content at 4 hours post trauma
      was inversely related to ADC variation (p < 0.0001). A significant increase in
      water content with low ADC, developed in the injured region in Ts, THHm (p <
      0.05) and THHs (p < 0.01) compared to Sham. Intracellular water rose in the whole
      brain in THH groups although more severely in the THHs (p < 0.01). Immediately
      after trauma ADC fell in the THH groups, but gradually increased in the THHm,
      whereas there was no recovery in THHs. The results indicate that the type of
      edema in the injured area, with and without superimposed secondary insult, is
      predominantly cytotoxic (cellular). Moreover, secondary insults act
      synergistically with focal injury to increase cellular water in both injured
      tissue and remote regions.

PMID- 11450024
TI  - Plasminogen activator inhibitor-1 in patients with ischemic stroke.
AB  - Low fibrinolytic activity may increase the risk of thrombosis. Plasminogen
      activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic system. We
      examined the PAI-1 levels in patients with ischemic stroke. Plasma levels of PAI
      1 were measured using enzyme-linked immunosorbent assay (ELISA) in 55 consecutive
      patients (age 60.2 +/- 11.4, 40 males and 15 females) with ischemic stroke. The
      PAI-1 assessments as well as neurological examinations using validated stroke
      scales were conducted at admission and 1 week, 1 month, and 3 months after
      stroke. Sex- and age-matched controls (+/- 4 years) underwent plasma PAI-1
      measurement once. Etiology of the stroke was classified using the Trial of Org
      10172 in Acute Stroke Treatment (TOAST) criteria. All pertinent stroke risk
      factors were recorded. All patients were contacted 3 years after stroke for
      recurrent vascular thrombotic disease. The plasma PAI-1 levels were 17.2 +/- 7.8
      IU at admission, 11.2 +/- 9.2 IU at 1 week, 14.4 +/- 7.9 IU at 1 month, and 17.8
      +/- 7.8 IU at 3 months among patients and 11.8 +/- 9.5 IU among controls (p
      values are < .002, .7, .12, and < .0005, respectively). As a rule, the
      neurological scores did not show a correlation to the PAI-1 levels. Presence of
      diabetes, hypertension, obesity, smoking, anticoagulant treatment, and sleep
      apnea did not affect the PAI-1 levels at any time point. Females had slightly
      higher PAI-1 levels. Age was a strong determinant for PAI-1 levels being higher
      in younger patients at every sampling time point (p values .02, .02, .02, and .03
      respectively). The etiology of the ischemic stroke did not have an impact on PAI
      1 levels. In 16 patients recurrent thrombosis had occurred. The high PAI-1 levels
      at admittance may reflect either an acute phase response or a chronic state.
      Normalized levels at 1 week and 1 month may be due to hospital diet,
      antithrombotic medication, weight loss, active physical therapy, and better care
      for diabetes. PAI-1 levels at 3 months after stroke did not predict recurrent
      thrombosis.

PMID- 11450025
TI  - Experimental study on brain oxygenation in relation to tissue water
      redistribution and brain oedema.
AB  - The aim of the present experimental research was to study brain oxygenation
      parameters in relation to tissue water movement and brain cortex oedema caused by
      focal brain ischemia. It has been demonstrated that local osmotic dehydration of
      the parietal brain cortex, mercury compounds (aquaporin inhibitors) and brain
      cortex oedema resulting from focal brain ischemia all influence extra-capillary
      oxygen transport lowering tissue respiration rates and oxygen transfer
      coefficients. The changes of brain oxygenation parameters in case of cortex
      ischemic oedema are reflected in the gas composition (oxygen and carbon dioxide
      partial pressure) of the blood in v. jugularis. A short course of hyperbaric
      treatment results in normalization of water content in the brain. The results are
      interpreted in terms of the functioning of tissue microcirculation that might
      participate, at the extra-capillary level, in brain oxygenation.

PMID- 11450026
TI  - Mn-SOD and Bcl-2 expression after repeated hyperbaric oxygenation.
AB  - To clarify the mechanism of ischemic tolerance induced by HBO, we investigated
      the effect of HBO on immunoreactivity to Bcl-2 and Bax, apoptosis-regulating
      protein, or Mn-SOD, a radical scavenging system, in the CA1 sector of the gerbil
      hippocampus. Pretreatment comprising, five sessions at 2 ATA (atmosphere
      absolute) every other day, but not that comprising, ten sessions at 3 ATA every
      day, caused significant increases in Bcl-2 and Mn-SOD immunoreactivity in the CA1
      sector compared with in the sham pretreatment group. No significant differences
      in Bax immunoreactivity and neuronal density in the CA1 hippocampal neurons was
      observed between the groups. These results suggest that protection against
      mitochondrial alterations after ischemia through Mn-SOD and/or Bcl-2 expression
      is related to the ischemic tolerance induced by repeated HBO pre-treatment.

PMID- 11450027
TI  - Glutathione homeostasis and leukotriene-induced permeability in human blood-brain
      barrier endothelial cells subjected to in vitro ischemia.
AB  - Ischemic alterations in the glutathione (GSH) redox system of the blood-brain
      barrier (BBB) may facilitate oxidative injury and formation of vasogenic brain
      edema. In this study, both the intra- and extracellular GSH contents of human
      cerebromicrovascular endothelial cells (HCEC) were reduced by 35% after exposing
      the cells to 4 h in vitro ischemia and 24 h-recovery. The
      intracellular/extracellular GSH ratio was not affected, indicating a constant
      rate of GSH efflux. The activities of the peroxide detoxifying enzymes,
      glutathione peroxidase and glutathione S-transferase, increased by 35%-50%,
      whereas the GSH regenerating enzyme, glutathione reductase, remained unchanged in
      ischemic HCEC. gamma-glutamyl transpeptidase (GGTP), a GSH catabolizing enzyme
      enriched in brain capillaries, was reduced by 30-50% in ischemic HCEC. The effect
      of in vitro ischemia on HCEC permeability was assessed by measuring sodium
      fluorescein clearance across a compartmentalized in vitro BBB model. Sodium
      fluorescein clearance across HCEC monolayers exposed to leukotriene C4 in the
      presence of the GGTP inhibitor, acivicin (1 microM), or after in vitro ischemia
      was increased by 60% and 30%, respectively, suggesting that oxidative stress and
      loss of GGTP may 'unmask' BBB permeabilizing actions of leukotrienes. These
      results indicate that oxidative stress and loss of GGTP activity in HCEC
      contribute to ischemic BBB disruption and vasogenic brain edema.

PMID- 11450028
TI  - Neurotrophic factors attenuate alterations in spinal cord evoked potentials and
      edema formation following trauma to the rat spinal cord.
AB  - Influence of brain derived neurotrophic factor (BDNF) and insulin like growth
      factor-1 (IGF-1) on spinal cord injury induced disturbances in spinal cord
      conduction, edema formation and cellular stress response was examined in a rat
      model. Pretreatment with BDNF or IGF-1 significantly attenuated the loss of SCEP
      negative amplitude seen immediately after spinal cord injury. In these
      neurotrophins treated rats, upregulation of heat shock protein (HSP 72 kD)
      immunoreactivity, a measure of cellular stress response and spinal cord edema
      formation were considerably reduced 5 h after injury. These results suggest that
      neurotrophic factors improve spinal cord conduction after trauma and this
      beneficial effect of growth factors may be related with their ability to
      attenuate trauma induced cellular stress response, not reported earlier.

PMID- 11450029
TI  - Spinal cord injury induced c-fos expression is reduced by p-CPA, a serotonin
      synthesis inhibitor. An experimental study using immunohistochemistry in the rat.
AB  - Influence of serotonin on upregulation of cellular-fos (c-fos) following a focal
      spinal cord injury was examined using immunohistochemistry in a rat model. Spinal
      cord injury was produced by making a unilateral longitudinal incision of the
      dorsal horn of the T10-11 segments. A focal lesion to the cord markedly
      upregulated c-fos immunohistochemistry at 5 h which was mainly located in the
      edematous regions of the cord in the injured as well as in the perifocal T9 and
      T12 segments. Pretreatment with p-CPA, a serotonin synthesis inhibitor,
      significantly attenuated the c-fos upregulation along with the edematous
      expansion of the cord. These results for the first time suggest that trauma
      induced release of serotonin and edema formation are important biological signals
      inducing c-fos expression.

PMID- 11450030
TI  - 1H-MR spectroscopic monitoring of posttraumatic metabolism following controlled
      cortical impact injury: pilot study.
AB  - Proton magnetic resonance spectroscopy (1H-MRS) has been increasingly utilised in
      experimental traumatic brain injury for characterisation of posttraumatic
      metabolic dysfunction. Following human brain injury pathological findings
      correlated with outcome measures. Combined with conventional T2-weighted MR
      imaging MRS is a sensitive tool to evaluate metabolic changes in brain tissue
      following trauma. Studies have been restricted so far to diffuse axonal injury
      models and fluid percussion injury. Using a high resolution scanner at 4.7 T, MRI
      combined with 1H-MRS was applied in a pilot study to the controlled cortical
      impact injury model of experimental brain contusion (CCII). Eight Sprague-Dawley
      rats were investigated, of which two served as controls. Four animals were
      injured 24 h after craniotomy, two investigated at 72 h post craniotomy. MRS/MRI
      indicated a transient brain oedema development and metabolic changes induced by
      the craniotomy itself. Following CCII MRI demonstrated that the area of contusion
      as well as the surrounding brain oedema increased twofold in size within 24 h (p
      < 0.05). MRS showed an immediate increase of N-acetylaspartate (NAA) and
      glutamate ipsilateral to the contusion and a drop of NAA on the contralateral
      side. MRS/MRI investigations in the CCII model demonstrated a potential to
      further elucidate the pathophysiology following traumatic brain contusion.

PMID- 11450031
TI  - Lipocortin-1 fails to ameliorate ischemic brain edema in the cat.
AB  - It has been reported that corticosteroids exert their anti-inflammatory action
      through de novo synthesis of phospholipase-inhibitory proteins called lipocortins
      (annexins). We postulated that the following may lessen the effectiveness of
      corticosteroids on acute ischemic brain edema: 1) lipocortins are induced several
      hours after administration of steroids; 2) de novo synthesis of lipocortins is
      suppressed in the ischemic brain; and 3) lipocortins induced systemically do not
      pass through the blood-brain barrier (BBB) to reach the sites of ischemic edema.
      To test this hypothesis, we examined whether dexamethasone, given long before
      ischemia or direct administration of recombinant lipocortin-1, combined with or
      without BBB opening, ameliorate ischemic brain edema. Three hours before
      occlusion of the middle cerebral artery (MCA) in the cat, 4 mg/kg of
      dexamethasone was injected intravenously. The animals were subjected to 4 hours
      of ischemia. Alternatively, 2 ug/ml (total volume 10 ml) of recombinant human
      lipocortin-1 (annexin-I) was perfused intermittently into the ischemic focus by
      catheterization into the MCA. Artificial opening of the BBB was performed by
      intra-arterial mannitol infusion. None of these strategies demonstrated
      amelioration of ischemic edema. We conclude that: Dexamethasone and recombinant
      lipocortin-1 seem unlikely to have robust effects on amelioration of acute
      ischemic edema.

PMID- 11450032
TI  - Lipocortin-1 fails to ameliorate cold-injury brain edema in the rat.
AB  - Based on evidence that corticosteroids exert their anti-inflammatory action via
      de novo synthesis of phospholipase A2 inhibitory proteins called lipocortins, we
      examined effects of high dose dexamethasone and recombinant human lipocortin-1
      (annexin-I) on cold-injury brain edema in the rat. Since it takes several hours
      for lipocortins to be induced, dexamethasone (10 mg/kg) was injected
      intraperitoneally 3 hours before cold injury. Recombinant lipocortin-1 was
      administered intraventricularly at three different doses (0.01 mg/kg, 0.05 mg/kg,
      or 0.1 mg/kg: total volume 20 microliters), or via the internal carotid artery at
      a dose of 10(-7) M (2 ml). To induce cold injury, a liquid-nitrogen-cooled probe
      was placed on the exposed dura of male Wistar rats (330-370 kg) for 1 minute.
      Specific gravimetry and/or a wet-dry weighing method were used for measurement of
      brain edema at 24 or 48 hours after lesion production. In the present study,
      dexamethasone and recombinant lipocortin-1 failed to attenuate edema formation.
      The anti-inflammatory effects of dexamethasone or exogenous lipocortin-1 seemed
      unlikely to affect cold-injury brain edema.

PMID- 11450033
TI  - Hepatocyte growth factor reduces infarct volume after transient focal cerebral
      ischemia in rats.
AB  - Hepatocyte growth factor (HGF) was originally discovered as a powerful mitogen
      for hepatocytes. HGF functions both as a neurotrophic factor as well as an
      angiogenetic factor. Furthermore, HGF has an anti-apoptotic effect on vascular
      endothelial cells. The present study examined the neuroprotective effect of HGF
      after transient focal cerebral ischemia in rats, in which an anti-apoptotic and
      an angiogenetic effect of HGF was assumed to contribute to the reduction of the
      infarct volume. The intraventricular administration of human recombinant HGF (90
      micrograms) significantly reduced the infarct volume after 120 minutes occlusion
      of both the right middle cerebral artery (MCA) and the bilateral common carotid
      arteries (CCAs). In a separate series of experiments, we investigated both the
      anti-apoptotic effect on neurons and the angiogenetic effect of HGF
      histopathologically. The number of survival neurons and vascular lumina in the
      HGF group were significantly higher than those in the vehicle group. A large
      number of TUNEL positive neurons were observed in the inner boundary of the
      infarct area in the vehicle group, whereas only a few TUNEL positive neurons were
      observed in a corresponding area in the HGF group. In the HGF group, Bcl-2
      protein was obviously represented in survival neurons as well as in vascular
      endothelial cells and in glial cells subjected to ischemia. These data suggest
      that HGF prevents apoptotic neuronal cell death by upregulating the production of
      Bcl-2 protein and by an angiogenetic effect in the central nervous system which
      affected transient focal cerebral ischemia.

PMID- 11450034
TI  - Clinical use of lidocaine for control of stroke oedema in the posterior cranial
      fossa accompanied by acute hydrocephalus.
AB  - Intravenous Lidocaine, in combination with steroid and Mannitol was used in 17
      critical cases to control posterior fossa stroke oedema with jeopardised upward
      or downward herniation. Lidocaine successfully provided time for observation to
      select 5 correct candidates out of 17, indicated for aggressive decompression
      surgery in addition to ventricular drainage for acute hydrocephalus. There is no
      'Golden-Rule' for this situation but the use of Lidocaine has a place in the
      management of it.

PMID- 11450035
TI  - Usefulness of niravoline, an arginine vasopressin inhibitor, on tumour-origin
      brain oedema.
AB  - Niravoline is a selective agonist of kappa-opioid receptors having potent
      aquaretic activity which may peripherally be mediated in animals. This effect of
      niravoline is thought to be due to inhibition of arginine vasopressin secretion.
      Niravoline does not cause an overt excretion of electrolytes that is seen with
      conventional diuretics, and it is anticipated that niravoline may prove useful in
      the treatment of oedema. In this study, effect of niravoline on tumour-origin
      brain oedema was investigated in a brain tumour model created by implantation of
      C6 glioma cells into the brains of Wistar rats. Five weeks after the tumour cell
      implantation, niravoline was administered i.v. at 1 mg/kg a total of four times
      at one-hour intervals. In the control group (i.e., saline or vehicle-treated
      rats), this brain tumour model was found to result in a statistically significant
      increase in the water content in selected brain regions remote from the tumour.
      Administration of niravoline inhibited the increase in the water content in such
      selected brain regions. Niravoline might be useful on tumour-origin brain oedema
      clinically.

PMID- 11450036
TI  - Broad-spectrum cation channel inhibition by LOE 908 MS reduces infarct volume in
      vivo and postmortem in focal cerebral ischemia in the rat.
AB  - Cation channels conduct calcium, sodium, and potassium, cations that are likely
      deleterious in the evolution of focal ischemic injury. Diffusion-weighted
      magnetic resonance imaging (DWI) is a powerful tool for evaluation of acute
      cerebral ischemia. We studied the effects of a novel, broad-spectrum inhibitor of
      several cation channels, LOE 908 MS, on acute ischemic lesion development with
      DWI and on cerebral infarct size using 2,3,5-triphenyltetrazolium chloride (TTC)
      staining postmortem. Eighteen male Sprague-Dawley rats underwent middle cerebral
      artery occlusion (MCAO) and were randomly and blindly assigned to either LOE 908
      MS (1 mg/kg bolus 30 min after MCAO and continuous i.v. infusion of 10 mg/kg for
      4 h thereafter) or vehicle. Whole-brain DWI was done before initiation of
      treatment and repeated every 30 min for the next 3.5 h. The animals were
      reperfused in the magnetic resonance imaging (MRI) scanner 90 min after MCAO. At
      24 h, the animals were killed, and the brains were cut into six 2-mm-thick slices
      and stained with 2% TTC. Percent hemispheric lesion volume (%HLV) was calculated
      for each animal. Physiological parameters, body weight, and premature mortality
      (3 in the placebo group and 1 in the treated group) did not differ between the
      groups. No hypotension, abnormal behavior, or other adverse effects were seen.
      Pretreatment, the DWI-derived %HLV did not differ between the groups (19.8 +/-
      6.2 in the control group and 17.9 +/- 7.9 in the treated group), whereas at 4 h
      after MCAO, it was significantly smaller in the treated group (21.8 +/- 15.4 vs
      40.4 +/- 15.5, p = 0.03). Postmortem, TTC-derived %HLV was significantly
      attenuated in the LOE 908 MS group (21.3 +/- 11.9 vs 50.1 +/- 10.7, p = 0.0001)
      and the neurological scores at 24 h were significantly better among the treated
      rats (2.1 +/- 1.5 vs 4.0 +/- 1.0, p < 0.02). LOE 908 MS significantly improved
      neurological outcome and reduced infarct size without observable effects in rats
      as demonstrated in vivo by DWI and confirmed postmortem by TTC staining. Blocking
      several distinct cation channels by LOE 908 MS showed significant
      neuroprotection.

PMID- 11450037
TI  - A glycine site antagonist ZD9379 reduces number of spreading depressions and
      infarct size in rats with permanent middle cerebral artery occlusion.
AB  - Spreading depressions (SDs) occur in experimental focal ischemia and contribute
      to lesion evolution. N-methyl-D-aspartate (NMDA) antagonists inhibit SDs and
      reduce infarct size. The glycine site on the NMDA receptor complex offers a
      therapeutic target for acute focal ischemia, potentially devoid of many side
      effects associated with competitive and non-competitive NMDA antagonists. We
      evaluated the effect of the glycine antagonist, ZD9379, on SDs and brain
      infarction. Male Sprague-Dawley rats (n = 18) weighing 290 to 340 g undergoing
      permanent middle cerebral artery occlusion (MCAO) were randomly and blindly
      assigned to receive drug or placebo: Group 1 (pre-MCAO treatment group, n = 5) a
      5 mg/kg bolus of ZD9379 over 5 minutes followed by 5 mg/kg/hour drug infusion for
      4 hours beginning 30 minutes before MCAO; Group 2 (post-MCAO treatment group, n =
      7) a 5 mg/kg bolus of ZD9379 30 minutes after MCAO followed by 5 mg/kg/hour drug
      infusion for 4 hours; and Group 3 (control group, n = 6) vehicle for 5 hours
      beginning 30 minutes before MCAO. SDs were monitored electrophysiologically for
      4.5 hours following MCAO by continuous recording of cortical direct current (DC)
      potentials and electrocorticogram (ECoG). Infarct volume was measured 24 hours
      after MCAO by 2,3,5 triphenyltetrazolium chloride (TTC) staining. Corrected
      infarct volume was 90 +/- 72 mm3 (mean +/- standard deviation) in Group 1, 105 +/
      46 mm3 in Group 2, and 226 +/- 41 mm3 in Group 3 (P < .001). The corresponding
      numbers of SDs in the 3 groups were 8.2 +/- 5.8, 8.1 +/- 2.5, and 16.0 +/- 5.1,
      respectively (P < .01). When all animals (n = 18) were analyzed, infarct volumes
      and the number of SDs were significantly correlated (r = .68, P = .002). This
      study demonstrated that ZD9379 initiated before or after MCAO significantly
      reduced the number of SDs and infarct volume in a permanent focal ischemia model,
      implying that ZD9379 is neuroprotective and its neuroprotective effect may be
      related to inhibiting ischemia-related SDs.

PMID- 11450038
TI  - Effects of inducible nitric oxide synthase inhibition on cerebral edema in severe
      hypertension.
AB  - In order to clarify the causative role of cytotoxic nitric oxide (NO) in
      hypertensive cerebral injury, the effects of inducible nitric oxide synthase
      (iNOS) inhibition on leukocytes and endothelial function were examined using
      stroke-prone spontaneously hypertensive rats (SHRSP). For the iNOS inhibition, S
      methylisothiourea (SMT) was administered to 12-week-old male SHRSP for 3 weeks.
      Immunohistochemical examination were carried out for the expression of
      intercellular adhesion molecule-1 (ICAM-1), glucose transporter-1 (GLUT-1),
      fibrinogen and glial fibrillary acidic protein (GFAP) in cerebral cortex. The
      effects of iNOS inhibition was also examined for Mac-1 expression by flow
      cytometric analysis. Plasma NO metabolites level was significantly lower in the
      SMT group than in the control group. Mac-1 expression was inhibited by SMT. In
      the SMT group, brain weight was significantly lower than in the control. By SMT
      administration, ICAM-1 expression was suppressed, GLUT-1 was enhanced, fibrinogen
      was decreased and GFAP was decreased as compared to those in control group. In
      hypertensive cerebral injury in SHRSP, iNOS-derived NO, mainly in activated
      leukocytes, could be an important causative factor for endothelial injury.

PMID- 11450039
TI  - Sphingolipid biosynthesis by L-PDMP after rat MCA occlusion.
AB  - L-PDMP (L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) exhibits
      stimulatory effects on glycosphingolipid biosynthesis and its neurotrophic
      actions in cultured neuron. The effects of intraperitoneal administration of L
      PDMP on sphingolipid metabolism and behavioral changes in the rat following
      permanent occlusion of the left middle cerebral artery (MCA) were investigated.
      The L-PDMP treatment induced increases in glucosylceramide (ganglioside
      precursor) and sphingomyelin (SM) levels in the ischemic cerebral cortex, and
      improved acquisition of memory and learning in the Morris water maze task. The
      pharmacological effects of L-PDMP have been proposed to have a significant
      activity on promoting cell survival and improving neural functions.

PMID- 11450040
TI  - Protective effect of a novel vitamin E derivative on experimental traumatic brain
      edema in rats--preliminary study.
AB  - Oxygen free radicals have been proposed to be one of the major mechanisms of
      secondary brain damage in traumatic brain injury. Protective effect by vitamin E
      against oxidative damage has attracted much attention. Recent studies have
      demonstrated a novel vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl
      2,5,7,8-tetramethylchroman-6-ol (TMG), has excellent water-solubility and
      antioxidant activity. The purpose of this study was to investigate protective
      effects of TMG on experimental traumatic brain edema (BE). Male Wistar rats were
      anaesthetized with chloral hydrate. Traumatic BE was produced by a cortical
      freezing lesion. Animals were separated into three groups: saline-treated rats (n
      = 4), TMG-treated (4 mg/kg) rats (n = 7) and TMG-treated (40 mg/kg) rats (n = 8).
      Saline or TMG was administered intravenously before lesion production. Animals
      were sacrificed at 6 hours after lesion production and the brain water content
      was determined by the dry-wet weight method. Half-life of TMG after intravenous
      administration of TMG was also investigated. The half life of TMG was
      approximately 5 minutes. TMG (40 mg/kg) significantly attenuated BE following
      cryogenic brain injury (p < 0.01). In conclusion, this preliminary study has
      demonstrated that a novel vitamin E derivative might be promising in the
      treatment of traumatic BE.

PMID- 11450041
TI  - Distinguishing between cellular and vasogenic edema in head injured patients with
      focal lesions using magnetic resonance imaging.
AB  - Having determined that edema and not vascular engorgement is the major factor
      leading to traumatic brain swelling, the objective of this study was to determine
      which type of edema, cellular or vasogenic, is responsible for increased tissue
      water in patients with focal lesions. Severely head injured patients (GCS 8 or
      less) were transported to imaging suites for measurement of brain water and
      apparent diffusion coefficient (ADC) using magnetic resonance technique. Cerebral
      blood flow by stable Xenon method was also measured in the regions of interest.
      Brain water was increased significantly in the hemisphere with lesion. The
      increase in water was associated with reduced ADC signifying a predominant
      cellular edema. The ADC in the contralateral hemisphere was near normal value.
      Cerebral blood flow values in the regions of interest were above ischemic levels
      suggesting that factors other than ischemia are responsible for the cytotoxic
      swelling in patients with focal injury.

PMID- 11450042
TI  - Comparison of NAA measures by MRS and HPLC.
AB  - This work investigates the accuracy of an in vivo estimation of absolute N-acetyl
      aspartate (NAA) concentrations by magnetic resonance spectroscopy (MRS) using
      cerebral water as an internal reference standard. Single-voxel, proton
      spectroscopy was carried out in two groups of rats (normal and diffuse head
      injury), using a PRESS sequence with TR = 3 s, TE = 135 ms. Fully relaxed water
      spectra and water-suppressed proton spectra were obtained from a 7 x 5 x 5 mm3
      volume of tissue. MRI-based brain water content measurements were also performed.
      Following MRS, HPLC determinations of NAA were carried out. In the normal rats
      the MRS yielded 10.98 +/- 0.83 mmol/kg w.w. vs 10.76 +/- 0.76 for HPLC with a
      mean absolute difference of 0.8. In the injured rats the corresponding results
      were 9.41 +/- 1.78 (MRS) and 8.16 +/- 0.77 (HPLC) with a mean absolute difference
      of 1.66. The in vivo absolute method accurately documented the temporal NAA
      changes compared to the NAA/Cr approach.

PMID- 11450043
TI  - Interstitial lactate in the peritraumatic penumbra of rat brain.
AB  - A traumatic brain tissue necrosis is expanding to approximately 150% within 24 h
      after lesion. This process is accompanied by marked reduction of the perifocal
      cerebral blood flow likely to activate anaerobic glycolysis from a reduced O2
      supply leading to an accumulation of lactic acid. The current study was carried
      out to assess the interstitial levels of lactic acid as a potential factor of
      secondary brain damage. A microdialysis probe was stereotactically implanted
      approximately 2 mm below the brain surface of the parietal cortex in Sprague
      Dawley rats (250-300 g bw; n = 6) in chloralhydrate anaesthesia. The position of
      the probe was controlled by histology. 24 h later a standardised cortical cold
      injury was induced above the probe in halothane/N2O anaesthesia. Dialysate (2
      microliters/min) was collected in 15 min intervals, starting 1 h prior to and
      continuing until 4 hrs after trauma. The lactate concentration in the dialysate
      was fluorometrically determined by an enzymatic assay. Under baseline conditions
      dialysate concentrations of 324 +/- 48 microM were observed. A release of lactate
      was not found initially after trauma. Between 70 and 105 min later, however, the
      interstitial lactate levels briefly increased to 416 +/- 34 microM (n.s.), while
      reaching baseline levels again thereafter. Thus, the current results do not
      confirm an increased accumulation of lactate in the interstitial compartment of
      the penumbra despite a marked perifocal hypoperfusion of the brain after focal
      injury. The transitory increase in lactate at 90 min after trauma is unlikely to
      have caused a severe tissue acidosis which might be held liable for the secondary
      growth of the brain lesion induced by the focal injury.

PMID- 11450044
TI  - Attenuation of secondary lesion growth in the brain after trauma by selective
      inhibition of the inducible NO-synthase.
AB  - In previous studies we have demonstrate that aminoguanidine pretreatment
      attenuates the secondary necrosis growth after focal brain trauma. Purpose of the
      present investigation was to elucidate the therapeutic potential of this iNOS
      inhibitor when administered post lesion. Sprague-Dawley rats were subjected to a
      highly standardized cortical freezing lesion and administered with aminoguanidine
      (100 mg/kg i.p.) 15 min and 8 hrs after trauma or with isotonic saline,
      respectively. Animals were assigned to one of three experimental groups. The
      animals of group I--which served as reference for the histomorphometric
      determination of the spread of the primary lesion--were sacrificed 5 min after
      trauma. Group II, receiving isotonic saline and group III with aminoguanidine
      were subjected to perfusion fixation 24 hrs after trauma for evaluation of the
      necrosis growth. In controls with saline, the volume of the cortical necrosis
      increased from 6.07 +/- 1.04 mm3 (5 min) to 8.39 +/- 1.57 mm3 at 24 hrs (group
      II) after trauma. Treatment with aminoguanidine (group III) led to significant
      attenuation of the expansion of the necrosis to 6.77 +/- 0.87 mm3 at 24 hrs.
      Thus, the pathological role of activation of the inducible NO-synthase in the
      phenomenon of secondary lesion growth is confirmed by the present data on iNOS
      inhibition. Attenuation of expansion of the lesion is achieved even when
      initiating therapy after trauma.

PMID- 11450045
TI  - Evidence for lactate uptake after rat fluid percussion brain injury.
AB  - Traumatic brain injury (TBI) places enormous early energy demand on brain tissue
      to reinstate normal ionic balance. Glucose declines and lactate increases after
      TBI as demonstrated in clinical and lab studies, suggesting increased glycolysis.
      This led us to hypothesize that high extracellular fluid (ECF) lactate may be
      beneficial after TBI. We measured cerebral dialysate lactate and glucose, and
      arterial lactate and glucose, before & after rat Fluid Percussion Injury (FPI)
      (2.06 +/- 0.13 atm) with and without i.v. lactate infusion (100 mM x 4.5 hours)
      to test the hypotheses that arterial lactate determines ECF lactate. 14C-lactate
      autoradiography was also performed, to demonstrate whether lactate is taken up by
      traumatized brain. RESULTS: Dialysate lactate was always significantly higher
      than arterial. After lactate infusion, both the dialysate and the arterial
      lactate were significantly increased (P < 0.0001). Dialysate lactate increased
      within 10 min. following FPI, with significantly higher values in the lactate
      infusion group (82% higher with lactate infusion after FPI). Dialysate glucose
      fell following FPI, with a more severe decline in the saline group (129% lower),
      suggesting lactate infusion preserves or "spares" glucose in ECF. In our
      autoradiographic study, i.v. 14C-lactate accumulated at the injury site, with
      levels 2-4 times higher than in contralateral cortex. In conclusion, arterial
      lactate augmentation thus increases brain dialysate lactate and results in less
      reduction in ECF glucose, after FPI. Infused lactate accumulates at the injury
      site, where metabolism is probably the greatest.

PMID- 11450046
TI  - Topical application of brain derived neurotrophic factor influences upregulation
      of constitutive isoform of heme oxygenase in the spinal cord following trauma an
      experimental study using immunohistochemistry in the rat.
AB  - Influence of brain derived neurotrophic factor (BDNF) on carbon monoxide (CO)
      production following spinal cord injury was examined using expression of the
      constitutive isoform of the enzyme hemeoxygenase-2 (HO-2) in a rat model. A
      longitudinal incision of the right dorsal horn on the T10-11 segment markedly
      increased the HO-2 immunostaining in the cord at 5 h. At this time period,
      breakdown of the blood-spinal cord barrier (BSCB) and edema formation were quite
      prominent. Repeated topical application of BDNF (20 microliters of a 1
      microgram/ml solution) over the exposed surface of the cord significantly
      attenuated the edematous expansion of the cord and the disturbances in the BSCB
      permeability. In BDNF-treated rats, expression of HO-2 immunoreactivity was
      considerably reduced. These results strongly suggest that BDNF is neuroprotective
      in spinal trauma and this growth factor has the capacity to attenuate CO
      production by downregulating HO-2 expression.

PMID- 11450047
TI  - Time profile of neuron specific enolase serum levels after experimental brain
      injury in rat.
AB  - The aim of this study was to investigate the time course of NSE serum levels
      after traumatic brain injury in rats. 65 male Wistar rats were subjected to
      severe cortical impact injury (100 PSI, 2 mm deformation). Blood samples were
      drawn directly after trauma, after 1 h, 6 h, 12 h, 24 h, and 48 h in the trauma
      group as well as in sham operated animals directly after craniotomy, after 6 h
      and after 48 h. NSE serum levels were estimated with a commercially available
      enzyme immuno assay (LIA-mat Sangtec). The control animals showed a NSE serum
      level of 8.82 micrograms/l (mean, n = 10). We demonstrated a time dependent
      release of NSE into the serum after trauma. The highest NSE serum values were
      detected six hours after trauma (31.5 micrograms/l, mean, n = 10). NSE serum
      level seems to reflect neuronal damage after cortical contusion in the rat in a
      time dependent manner.

PMID- 11450048
TI  - Isoflurane doubles plasma glutamate and increases posttraumatic brain edema.
AB  - Increased plasma and cerebral glutamate levels may contribute to posttraumatic
      edema formation. Since volatile anesthetics elevate plasma amino acid
      concentrations, the influence of isoflurane on arterial plasma glutamate levels
      and brain edema formation was investigated in brain-injured rats. Rats were
      anesthetized with chloral hydrate (380 mg/kg i.p.) or isoflurane (1.2-2.0 vol%)
      for four hours following controlled cortical impact injury. Isoflurane
      significantly increased arterial glutamate levels compared to chloral hydrate
      (124 +/- 12 vs. 60 +/- 5 microM; p < 0.005). At eight hours after trauma, water
      content was significantly increased in the traumatized hemisphere compared to the
      non-traumatized side (p < 0.005). In addition, four hours of isoflurane
      anesthesia caused a significant increase in brain water content of both
      hemispheres compared to chloral hydrate (80.1 +/- 0.1 vs. 79.6 +/- 0.1%; p <
      0.005). Prolonged isoflurane anesthesia is associated with a significant increase
      in arterial plasma glutamate levels and brain water content. This increase in
      brain water content must be considered when performing prolonged isoflurane
      anesthesia.

PMID- 11450049
TI  - Mechanical injury alters volume activated ion channels in cortical astrocytes.
AB  - Although astrocytic swelling is likely to mediate brain edema and high ICP after
      traumatic brain injury, the mechanism is not understood. We employed whole cell
      patch clamp electrophysiology and a stretch injury model to understand whether
      volume regulating ion currents are altered following cell injury. Mixed rat
      astrocytes and neurons were co-cultured on deformable silastic membranes. Mild
      moderate cell injury was produced using a timed pulse of pressurized air to
      deform the silastic substrates by 6.5 mm. Then, ion currents were recorded with
      patch clamp methods. Cells were held at -65 mV and were stepped to +10 mV to
      monitor current changes. RESULTS: In unstretched astrocytes, small amplitude
      currents were obtained under isotonic conditions. Hypotonic solution activated an
      outwardly-rectifying current which reversed near -40 mV. This current resembled a
      previously reported anion current whose activation may restore cell volume by
      mediating a net solute efflux. In contrast, stretch injured cells exhibited a
      large amplitude, nonrectifying current. This current was not due to non-specific
      ionic leakage, since it was fully suppressed by the cation channel blocker
      gadolinium. Activation of novel stretch-activated cation currents may exacerbate
      cell swelling in injured astrocytes. Stretch injured astrocytes thus express a
      dysfunctional cation current as opposed to an osmoregulatory anion current. This
      mechanism, if present in vivo, may contribute to the cytotoxic swelling seen
      after traumatic brain injury.

PMID- 11450050
TI  - Thyroid hormones in comatose patients with traumatic brain injury.
AB  - The objective was to study if thyroid hormones, cortisol, prolactin and brain
      injury marker levels were changed in traumatic brain injury (TBI) patients with
      changing levels of consciousness. We estimated the above named parameters in 32
      patients (27 men and 5 women aged 11-55). Admission Glasgow Coma Score was < 8.
      Follow-up period--30 days. The length of coma was 3 to 25 days. There were
      significant decreases in TSH, TBG, FT3 and F_levels (p < 0.05, for each) and a T3
      increase (as compared to very low preceding values) on day 1 before emergence
      from coma and considerable post-coma increase in TBG, FT3, TSH and F levels (p <
      0.001 each) on days 1-3 in patients with diffuse axonal injury (DAI). In patients
      with contusions and epidural and subdural hematomas (CH) T3 and T4 levels
      continued to fall until 4-6 postcoma days. TSH values significantly increased up
      to average normal ranges (p < 0.05) on days "-" 2 and "-" 1 before emergence from
      coma and remained so. Significantly lower levels of TSH, F and PRL were found in
      patients with CH in the mostly remote period (on days "-" 12-"-" 8) before
      emergence from coma in comparison with DAI patients. In blood the following
      correlations of examined parameters were established: between NSE and T3 (r = 
      0.39), NSE and FT3 (r = -0.59), TNF alpha and TBG (r = -0.64), TNF alpha and T3
      (r = -0.3) and S-100 and T3 (r = -0.3) (p < 0.05, for each). The results obtained
      confirmed a low T3 syndrome in comatose TBI patients. We demonstrated an
      objective and informative interdependence: the turning-point moment of the
      emergence from coma was accompanied by significant changes of examined hormone
      levels and brain injury marker levels. The results may serve as a base for
      recommending monitoring FT3 and T3 levels simultaneously with that of other
      injury markers and adequate T3 replacement therapy in the early posttraumatic
      period.

PMID- 11450051
TI  - Influence of the bradykinin B1/B2-receptor-antagonist B 9430 on the cerebral
      microcirculation and outcome of gerbils from global cerebral ischemia.
AB  - The influence of the bradykinin B1/B2 antagonist B 9430 on the cerebral
      microcirculation following global cerebral ischemia was investigated in a closed
      cranial window preparation in Mongolian gerbils by intravital fluorescence
      microscopy. Global cerebral ischemia (GCI) was induced by occlusion of both
      common carotid arteries for 15 min. Leukocyte-endothelium interactions, vessel
      diameters, and the segmental microvascular blood flow were observed by intravital
      microscopy before and up to three hours after global cerebral ischemia. Following
      the early reperfusion period the animals survived up to 4 days after ischemia.
      The neurological deficit and the body weight were assessed daily. On day 4
      animals were subjected to perfusion fixation and the brain was removed. Nerve
      cell damage from ischemia was quantified histologically in cortex, hippocampus,
      and striatum. Animals with treatment received the bradykinin B1/B2 receptor
      antagonist B 9430 before (i.v.), during, and after ischemia (s.c.) until the end
      of the experiment. The frequency of leukocytes (cells/100 microns x min) rolling
      along the venular endothelium post ischemia was significantly decreased (p <
      0.05) in treated animals as compared to untreated controls (33.0 +/- 6.2 vs. 8.5
      +/- 2.3) as well as the number of leukocytes attached to the endothelial surface
      (7.2 +/- 3.0 vs. 2.0 +/- 1.0, n.s.). The neuroscore on day 4 (pre-ischemic
      control: 22 points) was reduced to 13.4 +/- 3.2 in untreated animals, while to
      4.7 +/- 3.2 points in the treatment group. No differences between animals with
      and without treatment were found as to the number of viable neurons. Although
      bradykinin is released in the brain during global cerebral ischemia, its
      antagonisation does not improve outcome despite the effective inhibition of
      leukocyte-endothelium interactions.

PMID- 11450052
TI  - S-100b as a screening marker of the severity of minor head trauma (MHT)--a pilot
      study.
AB  - Due to its neural tissue specificity S-100b is considered as a screening marker
      of cerebral injury in head trauma patients. However, the occurrence and relevance
      of an increased S-100b serum level in minor head trauma (MHT) is still debated.
      Therefore, the purpose of our study was to evaluate the diagnostic utility of S
      100b measurements in a level I trauma center emergency room (ER). Eighty patients
      presenting with clinical symptoms of MHT (GCS score of 13-15, transitory loss of
      consciousness, amnesia, nausea) were prospectively recruited. Blood samples were
      drawn at 0 h, 6 h and 24 h after admission, and a cerebral computed tomography
      (CT) was performed. The reference group consisted of 10 patients with severe head
      injury (GCS score < 8), the control group of 20 healthy volunteers.
      Concentrations of S-100b in serum were determined by an immunoluminometric assay.
      The results were compared with the plasma levels of polymorphonuclear (PMN)
      elastase as an established general trauma marker. In the MHT group, the S-100b
      serum level revealed 1.26 +/- 0.57 ng/ml at study entry (73.46 +/- 47.53 min
      after trauma). In comparison, the S-100b concentration was significantly elevated
      in patients with severe head trauma (5.26 +/- 1.65 ng/ml, p = 0.009), but no
      significant difference became evident in relation to the control group (0.05 +/-
      0.01 ng/ml). Starting values of PMN elastase in plasma amounted to 66.40 +/-
      14.92 ng/ml in severe trauma, and to 60.52 +/- 10.75 ng/ml in MHT showing
      significant differences only in relation to the control group (23.36 +/- 1.53
      ng/ml). When correlated with the severity of the later clinical course, the first
      S-100b measurements exhibited steadily increasing values as demonstrated in MHT
      outpatients (0.29 +/- 0.11 ng/ml), MHT in-hospital patients (0.70 +/- 0.19 ng/ml)
      and MHT intensive care unit patients (5.03 +/- 3.18 ng/ml). PMN elastase levels
      revealed no significant differences concerning the three MHT subgroups. Thus, in
      contrast to the general trauma marker PMN elastase, assessment of the specific
      neuroprotein S-100b early after traumatic insult appears to be a promising
      laboratory marker for the prognosis of the severity of brain injury in MHT
      patients. Nevertheless, further investigations are required to better understand
      its predictive value.

PMID- 11450053
TI  - Influences of secondary injury following traumatic brain injury in developing
      versus adult rats.
AB  - Hypoxia and hypotension are both common findings following traumatic brain injury
      occurring with a frequency of up to 46% according to data of the Traumatic Coma
      Data Bank. In the present study the influence of secondary injury on intracranial
      pressure and the cardiovascular response is investigated in developing rats.
      Differences from adult rats are determined. Diffuse brain injury was produced in
      intubated and ventilated 17-20 days old Sprague-Dawley rats (N = 16) using a
      modification of the Marmarou-model. Hypoxia was induced by reducing O2
      concentration to 8% lasting for 15/30 min. Mean arterial blood pressure
      recordings and intracranial pressure recordings were performed continuously.
      Animals were divided into two groups, sustaining hypoxia alone (N = 9) and
      trauma/hypoxia (N = 7). The results were compared to readings in adult animals
      subjected to hypoxia (N = 5) and trauma/hypoxia (N = 5) (450 gm/150 cm).
      Immediately following the onset of hypoxia in the developing rat, MABP decreased
      from 76.5 +/- 13 mm Hg to 35.8 +/- 7 mm Hg. In the adult rat the decrease was
      more marked (from 93.3 +/- 8 mm Hg to 33.5 +/- 5.7 mm Hg) (p < 0.05). Mortality
      rate in developing rats with trauma/hypoxia was 43% with no significant change of
      ICP (from 13 +/- 5.2 to 22.3 +/- 11). All adult animals recovered following
      trauma/hypoxia with no relevant ICP-increase within one hour post-trauma. Hypoxia
      induces hypotension in adult and developing rats. However, developing rats appear
      to be more vulnerable to hypoxia associated with trauma.

PMID- 11450054
TI  - The role of decompressive craniectomy in the treatment of uncontrollable post
      traumatic intracranial hypertension.
AB  - The benefit of decompressive craniectomy for the treatment of uncontrolled post
      traumatic intracranial hypertension seems to be encouraging if medical management
      fails. We present our experience in 22 cases of cerebral edema due to head
      trauma. The edema alone was rarely the direct consequence of head trauma.
      Frequently it was associated with an acute subdural or extradural hematoma and
      contusion (with or without mass effect). First of all we treated the mass effect
      of the hematoma and contusion when the diameter was more than 3 cm. Intracranial
      pressure was monitored in the majority of patients. Bone decompression was
      performed in the operating theatre depending on the values of intracranial
      pressure. In our series 41% of patients had a good recovery, 18% a severe
      disability, 23% a vegetative state and 18% died. The findings showed that the
      bony decompression must be performed early before the situation becomes
      irreversible. We suggest that if intracranial pressure values remain greater than
      30 mmHg with cerebral perfusion pressure below 70 mmHg, despite vigorous anti
      edema therapy, decompressive craniectomy should be considered.

PMID- 11450055
TI  - The impact of acute hyponatraemia on severe traumatic brain injury in rats.
AB  - The effect of experimental acute hyponatraemia on severe traumatic brain injury
      (TBI) was studied in a modified impact-acceleration model. The cortical
      contusional volume was quantified by image analysis on serial sections, injured
      axons were visualized and quantified by beta-Amyloid Precursor Protein (beta-APP)
      immunohistochemical staining. Regional brain water content was estimated by the
      wet-dry weight method. The experiment was conducted in Group I (injury only) and
      Group II (injury followed by acute hyponatraemia). Comparison between the two
      groups showed that acute hyponatraemia significantly increased contusional volume
      (3.24 +/- 0.70 mm3 vs. 1.80 +/- 0.65 mm3, P = 0.009) and the number of injured
      axons (128.7 +/- 44.3 vs. 41.7 +/- 50.1, P = 0.04) in the right thalamus & basal
      ganglia region. Water content of the brain stem region was also significantly
      increased by acute hyponatraemia (73.71 +/- 0.14% vs. 72.28 +/- 0.93%, P =
      0.004). These results suggest that acute hyponatraemia potentiates secondary
      brain damage in severe TBI by augmentation of both focal contusion and diffuse
      axonal injury. The injured brain stem region is more susceptible to edema
      formation induced by experimental acute hyponatraemia.

PMID- 11450056
TI  - Validation of a closed head injury model for use in long-term studies.
AB  - To study pharmacotherapy of traumatic brain injury in rats, a modified closed
      head injury model was used that expresses clinically relevant features including
      intracranial hypertension and morphological alterations. Long-term survival under
      ethically acceptable conditions would greatly improve its clinical relevance. To
      ensure this goal with great reproducibility, the experimental protocol was
      adapted, in particular the impact-acceleration kinetics. Variations in impact
      acceleration conditions were obtained by modifying the stiffness of the impact
      site and changing the height of a 400 g weight dropped from 51.5 to 31.5 cm
      (51.5/400; 31.5/400). Impact and acceleration were measured with a force sensor
      incorporated in a rigid dummy-rat and an accelerometer mounted on the platform
      onto which the animals are positioned. Significant correlation was shown between
      impact and acceleration. Accelerations obtained in rats were significantly lower
      than those in the dummy. Unlike the 51.5/400 group, in the 31.5/400 group no
      mortality or cranial fractures were observed. In both groups intracranial
      pressure rose to pathological values immediately after trauma and remained
      elevated longer than 24 h. Diffuse axonal injury developed in all groups and
      remained present for at least 7 days. By reducing the impact-acceleration
      conditions, post-traumatic complications were diminished, while the clinically
      important features were maintained.

PMID- 11450057
TI  - Diffuse axonal injury with or without an evacuated intracranial hematoma in head
      injured patients. Are they different lesions?
AB  - The general classification of head injury proposed by Marshall et al., based on
      admission CT scan findings, might mask a group of patients who have Diffuse Brain
      Injury (DI) in addition to intracranial haematomas. The aim of this study was to
      assess possible differences in outcome with respect to the level of intracranial
      pressure (ICP) and cerebral perfusion pressure (CPP) between a group of patients
      with DI: III-IV (Marshall's classification) after the evacuation of an
      intracranial haematoma (group A) and another group with DI: III-IV in the absence
      of a mass lesion (group B). We prospectively studied 129 patients with isolated
      and closed severe head injury (GCS < 9). In group A (n = 61), the median
      percentage of hours with ICP > 20 mmHg and CPP < 70 mmHg was 42.8 and 18,
      respectively and 17 (28%) survived with GOS 4-5. In group B (n = 68), median
      values of 20 and 5.5 hours were obtained for ICP > 20 and CPP < 70 respectively,
      whilst 39 (57.3%) survived with favourable outcomes. When we analysed the effects
      of the DI: III-IV in both groups of patients, we found that the differences in
      percentage of time with ICP > 20 and CPP < 70 were statistically significant (p <
      0.01) and patients in group A had a higher morbidity and mortality (p < 0.05).
      This study has demonstrated that the levels of ICP, morbidity and mortality in
      patients with DI: III-IV and an evacuated mass lesion were higher than in
      patients with DI: III-IV without a mass lesion.

PMID- 11450058
TI  - Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in
      children: a preliminary report.
AB  - Adrenomedullin is a recently discovered 52-amino-acid peptide that is a potent
      vasodilator. Infusion of adrenomedullin increases regional cerebral blood flow
      and reduces infarct volume after vascular occlusion in rats. Adrenomedullin may
      represent an endogenous neuroprotectant since it is increased after focal brain
      ischemia. Cerebral hypoperfusion is present after traumatic brain injury (TBI) in
      children. We hypothesized that adrenomedullin levels would be increased in
      children with severe TBI. Total adrenomedullin concentrations were measured using
      a radioimmunometric assay. Thirty-six samples of ventricular cerebrospinal fluid
      (CSF) from 10 pediatric patients were collected during the first 10 days after
      severe TBI (GCS < 8). Control CSF was obtained from 5 children undergoing lumbar
      puncture, who had normal CSF parameters and no evidence of central nervous system
      infection. Patients underwent standard neuro-intensive care, including
      cerebrospinal fluid drainage. Data were analyzed using a univariate regression
      model. Adrenomedullin concentration was markedly elevated in CSF of children
      following TBI versus control (mean level 10.65 vs 1.51 fmol/ml, p = 0.006). All
      36 case samples had an adrenomedullin concentration above the median value for
      the controls (1.52 fmol/ml). We conclude adrenomedullin is elevated in the CSF of
      children following severe TBI. We speculate that it participates in the
      endogenous response to cerebral hypoperfusion after TBI.

PMID- 11450059
TI  - Low extracellular (ECF) glucose affects the neurochemical profile in severe head
      injured patients.
AB  - Glucose (Gluc) is the main energy source for the brain. After severe head-injury
      energy demand is massively increased and supply is often decreased. In pilot
      microdialysis studies, many patients with severe head-injury had undetectable
      glucose concentrations, probably reflecting changes in metabolism and/or reduced
      supply. We therefore investigated whether patients with low ECF glucose
      (criterion: < 50 microM for > or = 5 hrs), LOWgluc, differ from patients with
      higher glucose levels (NORMALgluc) We also tested the interrelationships between
      other parameters such as lactate, glutamate, K+, brain O2 and CO2, ICP, CPP, and
      CBF in these two groups. We found that patients with low ECF glucose, LOWgluc,
      have significantly lower lactate concentrations than patients with "normal"
      glucose, NORMALgluc, levels do. Spearman correlations between glucose and most
      other parameters were similar in both patient groups. However, glutamate
      correlated positively with glucose, lactate, brain CO2 and negatively with brain
      O2 in the NORMALgluc patient group, whereas glutamate did not significantly
      correlate with any of these parameters in the LOWgluc group. There was also no
      correlation between outcome and the dialysate glucose. The results indicate that
      low ECF glucose is almost always present in severe head-injury. Moreover, the
      lack of correlation between low glucose and outcome, however, suggests that other
      energy substrates, such as lactate, are important after TBI.

PMID- 11450060
TI  - Evolution of energy failure after repeated cerebral ischemia in gerbils.
AB  - We have examined the regional differences in the evolution of energy failure in
      experimental focal cerebral ischemia. In gerbil brain subjected to repeated
      unilateral common carotid artery occlusion, the tissue ATP content, pH and
      succinic dehydrogenase activity decreased at different rates after the
      circulation had been restored in various cerebral regions. Light microscopical
      infarction became apparent at different rates following the impairment of the
      energy metabolism in these regions. In brain cortex with selective neuronal
      necrosis, only minor alterations in energy metabolism were detectable over a 7
      day period following the restoration of the circulation. The present data show
      that the rate of energy failure is significantly different in various cerebral
      regions after repeated periods of cerebral ischemia in the gerbil. A slowly
      evolving impairment of the cerebral energy metabolism after circulation of the
      brain has been restored appears to be indispensable for the delayed formation of
      infarction after transient cerebral ischemia.

PMID- 11450061
TI  - On-line monitoring of substrate delivery and brain metabolism in head injury.
AB  - Head injury is associated with complex pathophysiological changes in metabolism.
      The objective of the study was to investigate these changes by applying on-line
      bedside monitoring of cerebral metabolism using microdialysis. Following approval
      by the Local Ethics Committee and consent from the next of kin, a microdialysis
      catheter was inserted into the frontal cortex of patients with severe head
      injury. Twenty-one patients were studied for 102.3 +/- 26.9 hours (mean +/- 95%
      confidence interval; total 89.4 patient monitoring days). The overall cerebral
      glucose (mean of means) was 1.63 +/- 0.31 mM with periods of undetectable glucose
      recorded. The cerebral lactate and lactate/pyruvate ratio were 4.69 +/- 0.61 mM
      and 29.9 +/- 3.73 respectively. Patients who died (n = 4) or who were severely
      disabled (not proceeding to rehabilitation, n = 5) had a tendency towards lower
      glucose (1.39 +/- 0.35 mM), higher lactate (5.10 +/- 1.02 mM) and higher
      lactate/pyruvate ratios (35.5 +/- 7.67) compared to patients with good outcome
      (home or proceeding to rehabilitation, n = 12, glucose 1.80 +/- 0.49 mM, lactate
      4.38 +/- 0.85 mM, lactate/pyruvate ratio 27.9 +/- 4.33). Trends in these
      metabolic parameters relating to outcome were identifiable. In the majority of
      patients, cerebral glutamate levels (overall mean of means 9.47 +/- 4.59 microM)
      were initially high and then declined to stable levels. Patients in whom the
      glutamate level remained elevated or in whom secondary rises in glutamate were
      seen had a poor outcome. The application of bedside analysis of microdialysis
      enables the progress of the patient to be monitored on-line. In addition to
      establishing trends of improving and deteriorating metabolism, the technique has
      the potential to monitor the effects of therapeutic manoeuvres on the
      biochemistry.

PMID- 11450062
TI  - Extracellular glutamate and aspartate in head injured patients.
AB  - Eighty-six patients in coma from a severe head injury underwent monitoring of
      extracellular concentrations of glutamate and aspartate by a microdialysis
      technique during the first few days after injury. The median value for glutamate
      was 7.4 microM (interquartile range 3.6-18.8 microM). The median value for
      aspartate was 2.4 microM (interquartile range 1.1-5.0 microM). Average values for
      the dialysate concentrations of glutamate and aspartate, were closely related to
      outcome (p < .001 and p = .002, respectively). Patients who died of their head
      injury had significantly higher dialysate glutamate and aspartate concentrations
      compared to patients who recovered to a Glasgow Outcome Score of good recovery or
      moderate disability. Dialysate glutamate and aspartate levels were also
      significantly related to type of injury (p = .008 and p = .004, respectively).
      The highest values were found in patients with gunshot wounds, followed by
      patients with evacuated and unevacuated mass lesions. Patients with diffuse
      injuries had the lowest values of glutamate and aspartate. These results suggest
      that excitatory amino acids may play a role in the evolution of injury to the
      brain after trauma.

PMID- 11450063
TI  - Substrate delivery and ionic balance disturbance after severe human head injury.
AB  - The most important early pathomechanism in traumatic brain injury (TBI) is
      alteration of the resting membrane potential. This may be mediated via voltage,
      or agonist-dependent ion channels (e.g. glutamate-dependent channels). This may
      result in a consequent increase in metabolism with increased oxygen consumption,
      in order to try to restore ionic balance via the ATP-dependent pumps. We
      hypothesize that glutamate is an important agonist in this process and may induce
      an increase in lactate, potassium and brain tissue CO2, and hence a decrease in
      brain pH. Further we propose that an increase in lactate is thus not an indicator
      of anaerobic metabolic conditions as has been thought for many years. We
      therefore analyzed a total of 85 patients with TBI, Glasgow Coma Scale (GCS) < 8
      using microdialysis, brain tissue oxygen, CO2 and pH monitoring. Cerebral blood
      flow studies (CBF) were performed to test the relationship between regional
      cerebral blood flow (rCBF) and the metabolic determinants. Glutamate was
      significantly correlated with lactate (p < 0.0001), potassium (p < 0.0001), brain
      tissue pH (p = 0.0005), and brain tissue CO2 (p = 0.006). rCBF was inversely
      correlated with glutamate, lactate and potassium. 44% of high lactate values were
      observed in brain with tissue oxygen values, above the threshold level for cell
      damage. These results support the hypothesis of a glutamate driven increase in
      metabolism, with secondary traumatic depolarization and possibly hyperglycolysis.
      Further, we demonstrate evidence for lactate production in aerobic conditions in
      humans after TBI. Finally, when reduced regional cerebral blood flow (rCBF) is
      observed, high dialysate glutamate, lactate and potassium values are usually
      seen, suggesting ischemia worsens these TBI-induced changes.

PMID- 11450064
TI  - Assessment of the variation in cerebrovascular reactivity in head injured
      patients.
AB  - Several indices have been reported which correlate with autoregulatory function
      [2, 3]. However, before critical thresholds for targeting therapy can be defined,
      a better understanding of the inherent variability of cerebrovascular reactivity
      as measured by these indices is required. In this study, patients had BP, ICP and
      bilateral MCA TCD velocity monitored before, during and after BP and CO2
      challenges, applied in a random order, with measurements taken within 48 hours of
      injury. Four indices of reactivity were calculated: the PRx, the CORRx and the
      FVreact & ICPreact. At 48 hours post-injury inter-patient variation in
      cerebrovascular reactivity, as measured by these indices, is large and injury
      specific factors remain important determinants of the variance. Within patient
      analysis has identified instances where the combined monitoring of the PRx and
      the CORRx may provide information about the function of pressure autoregulation
      and further study of the combined use of these two indices of reactivity is
      warranted.

PMID- 11450065
TI  - Non-invasive cerebral perfusion pressure (nCPP): evaluation of the monitoring
      methodology in head injured patients.
AB  - The method of direct calculation of cerebral perfusion pressure (CPP) as the
      difference between mean arterial pressure and intracranial pressure (ICP)
      produces a number, which not always adequately expresses brain perfusion. We
      investigated an alternative non-invasive method, based on waveform analysis of
      Transcranial Doppler blood flow velocity in Middle Cerebral Arteries (MCA). 25
      consecutive head injured patients, paralysed, sedated and ventilated were
      studied. Intracranial pressure (ICP) arterial blood pressure (ABP) were monitored
      continuously. The left and right MCAs were insonated daily (116 measurements)
      using a purpose-built transcranial Doppler monitor (Deltex Ltd, Chichester, U.K.)
      with software capable of the non-invasive estimation of CPP. Time averaged values
      of ABP, mean and diastolic flow velocities (FVm, FVd) were calculated and CPPe
      was computed as: ABP*FVd/FVm + 14. An absolute difference between real CPP and
      CPPe was less than 10 mm Hg in 82% of measurements and less than 13 mm Hg in 90%
      of measurements. The method demonstrated a high potential to detect both short
      term and long-term changes in CPP. The method is of potential benefit for the
      intermittent measurement and continuous monitoring of changes in brain perfusion
      pressure in situations where the direct measurement of CPP is not available or
      its reliability is in question.

PMID- 11450066
TI  - A study of the effects of using different cerebral perfusion pressure (CPP)
      thresholds to quantify CPP "secondary insults" in children.
AB  - Little is known about the incidence of secondary insults, particularly cerebral
      perfusion pressure insults, in children. The objectives of this study were to
      assess the duration of CPP insults at three different thresholds in children and
      to relate CPP insults to outcome. Eighteen children (age < 16, median & mean 8
      years) admitted to the Neurointensive Care Unit who had ICP, MAP and CPP
      continuously monitored were studied. Using the Edinburgh secondary insult
      analysis program, data was scanned for CPP insults at three different thresholds:
      CPP < 70 mmHg, < 60 mmHg and < 50 mmHg. Outcome was assessed using the Glasgow
      Outcome Scale. Thirty percent of the time CPP was between 60 and 70 mmHg, 21% of
      the time CPP was between 50 and 60 mmHg and 8% of the time the CPP was less than
      50 mmHg. Compared with adults, there was more than twice the incidence of CPP
      insults in all threshold groups. BP remained relatively stable above 70 mmHg
      across all three CPP threshold groups. However, ICP increased slightly on average
      from about 13-->17 mmHg when CPP decreased from the < 70 to < 60 mmHg group (p <
      0.001). There was a marked increase in ICP to greater than 30 mmHg on average in
      the CPP < 50 mmHg group (p < 0.001). CPP insults less than 70, 60 and 50 mmHg do
      occur commonly in children, a larger dataset and possibly longer term follow up
      measures will be needed to identify potentially treatable physiological factors
      most effecting the outcome of children.

PMID- 11450067
TI  - Does an increase in cerebral perfusion pressure always mean a better oxygenated
      brain? A study in head-injured patients.
AB  - The adequate management of cerebral perfusion pressure (CPP) continues to be a
      controversial issue in head-injured patients. The purpose of our study was to
      test two hypotheses. The first was that in patients with a CPP below 70 mm Hg,
      oxygen delivery is compromised and that therefore signs of tissue hypoxia would
      be reflected in low PtiO2 measurements. The second hypothesis was that
      manipulating mean arterial blood pressure to increase CPP improves oxygen
      delivery, particularly in patients with a CPP below 70 mm Hg. Twenty-five
      moderately or severely head-injured patients were included in the study. In all
      of them PtiO2 was monitored in the non-injured hemisphere using the Licox system
      (GMS, Kiel-Mielkendorf, Germany). Arterial hypertension was induced with
      phenylephrine 29 times. To quantify the effect of increasing mean arterial blood
      pressure (MABP) on oxygen delivery to the brain, the PtiO2-BP index was
      calculated (PtiO2-BP index = delta PtiO2/delta MABP). In 16 tests (55%) baseline
      CPP was above or equal to 70 mm Hg and in the remaining 13 (45%) it was below 70
      mm Hg. Mean increase in MABP after phenylephrine was 23.7 +/- 10.2 mm Hg. Mean
      PtiO2 was 29.5 +/- 14.7 mm Hg in patients with a basal CPP of below 70 mm Hg and
      28.9 +/- 10.6 mm Hg in patients in the high CPP group. These differences being
      not statistically significant. The PtiO2-BP index was 0.29 +/- 0.23 in patients
      with a basal CPP of below 70 mm Hg and in patients with a CPP of above 70 mm Hg
      this index was 0.16 +/- 0.11 Hg. These differences were not statistically
      significant (Student's t-test, P = 0.09). In our study a low PtiO2 was not
      observed in patients with marginally low CPPs (48-70 mm Hg) and readings below 15
      mm Hg were observed in cases with both normal or supranormal CPPs. We conclude
      that episodes of low PtiO2 could not be predicted on the basis of CPP alone. On
      the other hand, raising CPP did not increase oxygen availability in the majority
      of cases, even if the CPP was markedly improved.

PMID- 11450068
TI  - Continuous monitoring of ICP and CPP following ICH and its relationship to
      clinical, radiological and surgical parameters.
AB  - Sixty-two patients with a spontaneous supratentorial haemorrhage had continuous
      Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) monitoring. In
      addition to the recordings of physiological data their past medical history,
      presenting neurological state, Computed Tomograph (CT) findings, daily Glasgow
      Coma Score (GCS) and outcome were noted. The mean age was 57.6 years (sd 13.3).
      Onset of recording, after ictus was at a mean of 32.6 hours (sd 26.0). Average
      length of recording was 62.0 hours (sd 39.8). Thirty-one patients had evacuation
      of haematoma, 6 insertion of External Ventricular Drain (EVD). Preoperative
      measures of ICP were significantly related to delayed neurological deterioration,
      death within three days and Glasgow Outcome Scale (GOS) at neurosurgical
      discharge. No such relationships existed with preoperative measures of CPP and
      neither ICP nor CPP was related to outcome at 6 months. Post-operative measures
      of both ICP and CPP demonstrated a significant relationship with death within
      three days of ictus and GOS at neurosurgical discharge. Again no relationship
      existed with these parameters and outcome at six months. Surgical evacuation of
      haematoma acted to significantly reduce ICP and improve CPP. Given that these
      factors seem to be related to deterioration, death and early outcome, it would
      seem that surgery could play a role in reducing mortality and improving outcome
      following Intra cerebral Haemorrhage (ICH).

PMID- 11450069
TI  - Neuromuscular blocking agents in neurointensive care.
AB  - INTRODUCTION: Intensive care treatment of patients with severe head injury is
      aimed at preventing secondary injury. One of the cornerstones in this treatment
      is sedation and ventilation. Use of Neuromuscular Blocking Agents (NBA) has
      gained widespread use as part of the protocol for maintaining normal intracranial
      pressure values, without class 1 evidence for the efficacy of the treatment.
      METHODS: We examined data of the use of NBA as infusion during ventilator
      treatment, and IntraCranial Pressure (ICP) measurements in the database from the
      international multicenter randomized double blind trial of the NMDA receptor
      antagonist Selfotel. No specific mode of sedation was recommended in the study
      protocol. RESULTS: Of the 427 patients enrolled in the study 326 had a full data
      set, 138 received NBA during their stay in the ICU. There were no statistical
      difference in demographic data between the two groups. During their stay in the
      ICU, patients who received NBA had a median of 13.5 hours with a recorded ICP
      above 20 mm Hg, patients who did not receive NBA had a median of 6.5 hours with
      ICP above 20 mm Hg (p < 0.05). CONCLUSION: Our data challenges the concept of
      using NBA as part of a routine sedation strategy in treatment of patients with
      severe head injury.

PMID- 11450070
TI  - Indomethacin and cyclosporin a inhibit in vitro ischemia-induced expression of
      ICAM-1 and chemokines in human brain endothelial cells.
AB  - Brain inflammation has been implicated in the development of brain edema and
      secondary brain damage in ischemia and trauma. Mechanisms involved in leukocyte
      infiltration across the blood-brain barrier are still unknown. In this study, we
      show that human cere-bromicrovascular endothelial cells (HCEC) subjected to a 4 h
      in vitro ischemia (hypoxia + glucose deprivation) followed by a 4-24 h recovery
      express elevated levels of ICAM-1, IL-8, and MCP-1 mRNAs (semi-quantitative RT
      PCR) and secrete increased amounts of the immunoreactive chemokines IL-8 and MCP
      1 (ELISA). The ischemia-induced expression of ICAM-1 in HCEC, and the
      expression/release of IL-8 and MCP-1 in HCEC were abolished by the non-steroid
      anti-inflammatory drug, indomethacin (100-300 microM). The immunosuppressant
      cyclosporin A (50 microM) partially reduced the ischemia-stimulated IL-8 and MCP
      1 secretion by HCEC. Both indomethacin and cyclosporin A also inhibited the
      ischemia-induced neutrophil chemotaxis elicited by HCEC media. The study
      indicates that in vitro ischemia augments the expression of adhesion molecules
      and leukocyte chemoattractants at the site of the BBB. This ischemic pro
      inflammatory activation of HCEC may constitute a key event in initiating post
      ischemic inflammation, and it can be suppressed by the anti-inflammatory drugs,
      indomethacin and cyclosporin A.

PMID- 11450071
TI  - The role of nitric oxide in reoxygenation injury of brain microvascular
      endothelial cells.
AB  - OBJECT: The role of nitric oxide (NO) in reperfusion injury of the brain is still
      controversial. The authors demonstrate that NO injures the brain capillary
      endothelial cells in a reoxygenation state by the formation of peroxynitrite.
      MATERIALS AND METHODS: 1) Rat brain capillary endothelial cells (BCECs) were
      isolated by a two-step enzymatic purification method. The BCECs were identified
      by the presence of factor VIII. 2) Anaerobic cell preparations were achieved by
      purging under nitrogen gas with 0.5% CO2 at 37 degrees C for 20 minutes and then
      reoxygenating in an incubator. To ascertain the degree of BCEC injury after
      anoxia and reoxygenation, lactate dehydrogenase (LDH) release was measured. The
      production of NO was measured by the Griess method. 3) The cell-protective
      effects of superoxide dismutase (SOD), NG-nitro-L-arginine (L-NAME), and S-Methyl
      ITU (i-NOS blocker) were studied. RESULTS: 1) Both L-NAME and SOD protected the
      cells from reoxygenation injury. The protective effect of L-NAME was dose
      dependent. S-Methyl-ITU did not protect the cells. 2) The NO production after
      anoxia/reoxygenation was blocked by L-NAME. CONCLUSION: NO from the BCEC can
      injure the cells themselves through the formation of peroxynitrite under
      anoxia/reoxygenation conditions. Increased NO production after anoxia can be
      attributed to the induction of e-NOS.

PMID- 11450072
TI  - The use of decompressive craniectomy for the management of severe head injuries.
AB  - The aim of Neurosurgical care is to minimise the secondary brain damage that
      occurs after a severe head injury. This includes the evacuation of an
      intracranial space occupying haematoma, the reduction of intracranial volume,
      external ventricular drainage with hydrocephalus, and conservative therapy to
      reduce intracranial pressure (ICP) and to maintain tissue oxygen p(ti)O2. When
      conservative treatment fails, a decompressive craniectomy might be successful in
      lowering ICP. From September 1997 until April 1999 we operated on 128 patients
      with severe head injuries. 19 patients (15%) were treated by means of a
      decompressive craniectomy. The prognosis after decompression depends on clinical
      signs and symptoms on admission, patients' age and the existence of major
      extracranial injuries. Our guidelines for decompressive craniectomy after failure
      of conservative intervention and evacuation of space occupying hematomas
      included: a patient's age below 50 years without multiple trauma or a patient's
      age below 30 years in the presence of major extracranial injuries; severe brain
      swelling on CT scan (primary brainstem injuries were excluded). In 8 patients
      conservative 1TU treatment had failed.

PMID- 11450073
TI  - Transcranial Doppler ultrasonography (TCD) in ventilated head injured patients:
      correlation with stable xenon-enhanced CT.
AB  - Disturbance of cerebral vasomotor regulation has been shown to be associated with
      the severity of traumatic brain injury (TBI). The transient hyperaemic response
      (THR) test is a test of the pressure autoregulatory response in terms of cerebral
      blood flow velocity after a brief carotid artery compression. Correlating with
      the test of cerebral vascular reactivity (CVR) to carbon dioxide by means of
      passive hyperventilation suggested that the THR test is a simple clinical test
      for the assessment of cerebral haemodynamic status in head-injured patients.

PMID- 11450074
TI  - Continuous assessment of cerebral autoregulation--clinical verification of the
      method in head injured patients.
AB  - Previously, using transcranial Doppler ultrasonography, we investigated whether
      the hemodynamic response to spontaneous variations in cerebral perfusion pressure
      (CPP) provides reliable information about cerebral autoregulatory reserve. In the
      present study we have verified this method in 166 patients after head trauma.
      Waveforms of intracranial pressure (ICP), arterial pressure and transcranial
      Doppler flow velocity (FV) were captured daily over 0.5-2.0 hour periods. Time
      averaged mean flow velocity (FV) and CPP were resolved. The correlation
      coefficient indices between FV and CPP (Mx) were calculated over 3 minutes
      epochs, and averaged for each investigation. An index of CBF (flow velocity
      diastolic to mean ratio) was calculated independently for each investigation. Mx
      depended on CPP (p < 0.0001) increasing to positive values when CPP decreased
      below 60 mm Hg. This threshold coincided with an averaged breakpoint for
      autoregulation, expressed by the index of CBF. Mx depended on outcome following
      head injury stronger than the Glasgow Coma Score on admission (ANOVA, F values 18
      and 15 respectively; N = 166). In patients who died, cerebral autoregulation was
      disturbed during the first two days following injury. These results indicate an
      important role for the continuous monitoring of autoregulation following head
      trauma.

PMID- 11450075
TI  - False autoregulation (pseudoautoregulation) in patients with severe head injury.
      Its importance in CPP management.
AB  - False autoregulation has been described as an alteration of autoregulation in
      which the apparent maintenance of a constant cerebral blood flow (CBF) when
      increasing cerebral perfusion pressure (CPP) is due to an increase in brain
      tissue pressure. The objective of our study was to investigate how often false
      autoregulation occurred in patients with a severe head injury. In forty-six
      patients with a moderate or severe head injury autoregulation was studied using
      arteriojugular differences of oxygen (AVDO2) to estimate changes in CBF after
      inducing arterial hypertension with phenylephrine. Changes in mean arterial blood
      pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP)
      and AVDO2 were calculated before and after inducing hypertension. Ninety-five
      episodes of provoked hypertension were studied in 46 patients. In 28 tests
      (29.5%) a constant or even reduced CBF was detected simultaneously with a median
      increase in parenchymal ICP of 8.5 mm Hg (false autoregulation). In this group
      the median of the induced increase in MABP was 20.6 mm Hg with a median increase
      in CPP of 11.5 mm Hg. From our data we can conclude that false autoregulation is
      frequently found in patients after a severe head injury. Increasing MABP to
      obtain a better CPP in these patients is not beneficial because CBF is not
      modified or may even be reduced.

PMID- 11450076
TI  - Multi-centre assessment of the Spiegelberg compliance monitor: preliminary
      results.
AB  - Acute brain injury states (e.g. head injury, subarachnoid haemorrhage) show clear
      inverse relationships of ICP vs compliance, with ICP instability at times of
      lower compliance states. Variance in compliance values is large in hydrocephalus
      where ICP is relatively lower and compliance higher. Nonetheless, early
      experience shows that compliance data influence decisions on CSF diversion
      treatments. Future work will focus on the ability of intracranial compliance to
      predict ensuing ICP instability and methodological refinement for monitoring
      patients who have higher compliance states.

PMID- 11450077
TI  - Intracranial hypertension influences the resolution of vasogenic brain edema
      following intracerebral hemorrhage.
AB  - Aim of the current study was to investigate the influence of intracranial
      hypertension on the resolution of vasogenic brain edema following intracerebral
      hemorrhage. An intracerebral hematoma was induced by 500 microliters of blood
      injected into the left frontal lobe of rabbits (n = 25). Na(+)-fluorescein
      (MW376) and Texas-Red-albumin (MW67.000) were administered intravenously as edema
      markers. By using a closed cranial window for superfusion of the brain surface
      and a ventriculo-cisternal perfusion the clearance of both fluorescence markers
      was measured in the CSF-effluates up to 8 hours using spectrophotometry. ICP was
      adjusted between 2-6 mmHg (low pressure, n = 10), 8-12 mmHg (moderate pressure, n
      = 10) or 14-20 mmHg (high pressure, n = 5). In all groups Na(+)-fluorescein
      started to accumulate at 60 min after induction of the hematoma in the
      subarachnoid space, while at 90 min in the ventricular system. In the low
      intracranial pressure group Na(+)-fluorescein (mean +/- SEM) in the ventricular
      system amounted to 1.47 +/- 0.42 nmol as compared to 1.34 +/- 0.41 nmol in the
      moderate, or 0.38 +/- 0.11 nmol in the high intracranial pressure group. In the
      subarachnoid space the marker reached 1.96 +/- 0.57 nmol, 4.15 +/- 1.28 nmol, or
      0.96 +/- 0.32 nmol, respectively. In conclusion, the data demonstrate that
      vasogenic edema induced by an intracerebral hematoma is cleared into both CSF
      compartments, albeit with delay into the ventricular system. Edema resorption
      occurred earlier and to a higher extent into the subarachnoid space as compared
      to the ventricular system. Further, edema resorption is influenced by the actual
      intracranial pressure, with marked inhibition by a high intracranial pressure.

PMID- 11450078
TI  - Induction of colligin may attenuate brain edema following intracerebral
      hemorrhage.
AB  - Brain edema plays an important role in the secondary brain injury following
      intracerebral hemorrhage (ICH). Edema formation after ICH has been linked to
      thrombin toxicity. Therefore, the induction of endogenous serine protease
      inhibitors, which inhibit thrombin prior to ICH may limit edema formation. This
      study examines whether injection of a low dose of thrombin upregulates such
      inhibitors and induces tolerance to subsequent ICH. Rats received intracerebral
      infusions of either one unit thrombin or saline into the right caudate nucleus.
      After seven days, the rats were either (A) used to examine colligin (a serine
      protease inhibitor) induction by Western blot analysis, immunohistochemistry and
      immunofluorescent double labeling, (B) to determine brain water content, or (C)
      they received a second injection of 50 microL blood and brain edema was
      determined one day later. Intracerebral infusion of thrombin caused a marked
      upregulation of colligin, a serine protease inhibitor, in the ipsilateral basal
      ganglia. Immunocytochemistry and immunofluorescent double labeling showed that
      colligin was induced in astrocytes. Infusion of this dose of thrombin alone did
      not affect brain water content but it significantly attenuated subsequent ICH
      induced brain edema (79.0 +/- 0.5 vs. 81.4 +/- 0.9%, P < 0.01). Our results
      demonstrate that low doses of thrombin upregulate brain colligin levels and
      attenuate edema formation induced by ICH.

PMID- 11450079
TI  - Oxyhemoglobin produces necrosis in cultured smooth muscle cells.
AB  - OBJECT: Myonecrosis in the tunica media, which is defined morphologically, is one
      of the most striking alterations in the cerebral arterial wall following
      subarachnoid hemorrhage (SAH). In this study, oxyhemoglobin (OxyHb) was added to
      cultured rat aortic smooth muscle cells to determine the pattern of cell death by
      morphological and biochemical techniques. METHODS: Confluent rat aortic smooth
      muscle cells were treated with OxyHb in a concentration- and time-dependent
      manner. Cell density was assayed by counting the number of cells that attached to
      the culture dishes after exposed to OxyHb. To identify cell death pattern, DNA
      analysis, electron microscopy, and Western blotting using poly (ADP-ribose)
      polymerase (PARP) antibody were performed. CONCLUSIONS: OxyHb decreased cell
      density in a concentration- and time-dependent manner. DNA analysis showed a
      smear pattern characteristic of cell necrosis. Transmission electron microscopy
      demonstrated disintegration of cell membrane and destruction of cell organelles.
      No apoptotic changes, such as condensation of chromatin or apoptotic bodies were
      observed. Western blotting using PARP antibody revealed that 116 kDa PARP was not
      cleaved to 85 kDa, an apoptosis-related fragment. These results demonstrated
      morphologically and biochemically that OxyHb induced necrosis, not apoptosis, in
      cultured smooth muscle cells.

PMID- 11450080
TI  - Thrombin preconditioning, heat shock proteins and thrombin-induced brain edema.
AB  - Intracerebral injections of high concentrations of thrombin cause brain edema
      but, in vitro, low concentrations of thrombin may be neuroprotective. This study
      investigated whether a low dose of thrombin might induce tolerance to subsequent
      large doses of thrombin (thrombin preconditioning; TPC) in a manner analogous to
      ischemic preconditioning. The study involved five parts. The first tested the
      effect of intracerebral infusion of a small dose (1 U) of thrombin on brain water
      content. In the second part, the effect of such a small dose of thrombin on
      subsequent edema formation from a large dose of thrombin (5 U) was evaluated. The
      time course of TPC was examined in the third part. In the fourth part, heat shock
      protein (HSP) 27, HSP32 and HSP70 were quantitated by Western blotting analysis
      while the fifth identified the cell types expressing HSPs. Injection of a low
      dose of thrombin alone did not cause brain edema. However, TPC significantly
      attenuated the edema induced by a subsequent injection of a large dose of
      thrombin. This effect of TPC was abolished by co-injection of a thrombin
      inhibitor, hirudin. The maximal effect of TPC on edema formation was seven days
      after pretreatment. This time course was similar to that for a marked up
      regulation in astrocytic HSP27. TPC also induced HSP32, but this effect occurred
      earlier than the effect on edema formation. TPC had no effect on HSP70. These
      results suggest that thrombin-induced brain tolerance may be related to HSP27
      induction.

PMID- 11450081
TI  - Changes in cerebral blood flow as measured by HMPAO SPECT in patients following
      spontaneous intracerebral haemorrhage.
AB  - Lack of an effective treatment for spontaneous intracerebral haemorrhage (ICH) is
      partly because the mechanism of neuronal damage in ICH is not fully understood.
      Animal experiments have shown that there is a zone of ischaemia and oedema around
      the haematoma which can be reduced by early evacuation of the mass lesion. We set
      out to study Cerebral Blood Flow (CBF) changes in patients with ICH. We present
      data on 13 patients (mean age 60). SPECT scans were performed within 48 hours of
      ictus and 4-7 days later. Four patients had surgical evacuation of the clot; 9
      were managed conservatively. The ratio of uptake of the isotope in the cerebral
      hemisphere containing the haematoma to the isotope uptake in the contra-lateral
      (un-affected) cerebral hemisphere was taken as an index of perfusion of the
      affected cerebral hemisphere. The perfusion index of the affected hemisphere
      improved between the first and the second scans in all the surgically treated
      patients; in the conservatively managed group, it was worse in 6 patients, the
      same in 1 and very slightly better in 2. There was an overall mean improvement of
      3.87% in the surgical group, and an overall mean deterioration of 3.61% in the
      medical group. This data suggests that surgical evacuation of the clot may
      improve perfusion in the ipsilateral cerebral hemisphere in ICH. It underlines
      the importance of a prospective randomised trial to assess the value of surgery
      in patients with ICH. The Surgical Trial in Intracerebral Haemorrhage (STICH) is
      currently underway worldwide. We also describe the application of Difference
      Based Region Growing (DBRG) to SPECT image analysis. This method overcomes the
      difficulties posed by 1) the presence of a mass lesion and 2) surgical evacuation
      of haematoma.

PMID- 11450082
TI  - Surgical trial in intracerebral haemorrhage (S.T.I.C.H).
AB  - The International Surgical Trial in Intracerebral haemorrhage has been set up to
      determine the role of surgery in spontaneous supratentorial intracerebral
      haemorrhage. This is an interim report as the results will remain blinded until
      all patients have been recruited and followed up.

PMID- 11450083
TI  - Postischemic hypothermia attenuates apoptotic cell death in transient focal
      ischemia in rats.
AB  - Hypothermia confers potent neuroprotection against ischemic injury. Attenuation
      of apoptosis by hypothermia can be one of the responsible mechanisms. In this
      study, in situ DNA nick-end labeling (TUNEL) and immunostaining of Bax protein
      were performed to evaluate the effect of postischemic hypothermia on apoptotic
      cell death, employing rodent transient focal ischemia. Animals received 1 hour of
      transient focal ischemia. Brain temperature was maintained at 37.5 +/- 0.5
      degrees C during ischemia. Immediately after reperfusion, animals were assigned
      to either a normothermic or hypothermic group. In hypothermia, animals were
      cooled and brain temperature was lowered to 34.5 +/- 1.0 degrees C. Prolonged
      hypothermia was maintained for 16 hours and animals rewarmed. In both groups,
      TUNEL and immunostaining of Bax was performed. In normothermia, the number of
      TUNEL positive cells reached the peak at 2 days after ischemia and decreased
      gradually. In hypothermia, the peak was shifted to 3 days after ischemia. The
      number of TUNEL positive cells in hypothermia was persistently below that of
      normothermia. Similarly, in hypothermia, immunostaining of Bax showed attenuated
      immunoreactivity compared with that in normothermia. In conclusion, postischemic
      hypothermia reduced both the number of TUNEL positive cells and immunoreactivity
      of Bax, which may be one of the responsible mechanisms with which hypothermia
      exerts neuroprotection.

PMID- 11450084
TI  - Effects of hypothermia on intracranial hemodynamics and ischemic brain damage
      studies in the rat acute subdural hematoma model.
AB  - Brain ischemia is the leading pathophysiological mechanism in the development of
      secondary brain damage after subdural hematoma (SDH). Hypothermia has been used
      as the effective neuroprotective treatment in clinical and laboratory studies of
      ischemic brain injury. In this study, we have examined the rat acute SDH model to
      assess the effect of hypothermia upon intracranial hemodynamics and also upon
      ischemic brain injury 4 hours after the induction of hematoma. Moderate
      hypothermia (32 degrees C) did not affect the intracranial pressure nor cerebral
      perfusion pressure, and it significantly reduced cortical brain edema formation
      underneath the hematoma (80.88 +/- 0.17%; p < 0.01) compared with the
      normothermic control group (81.65 +/- 0.52%). This reduction in brain edema
      formation was comparable to the result of MK-801 (2 mg/kg) treatment (80.95 +/-
      0.35%; p < 0.01). Ischemic brain damage detected by H-E staining was also
      significantly reduced in the hypothermia and MK-801 treated groups (59.1 +/- 12.3
      mm3 and 66.4 +/- 13.8 mm3; p < 0.01 and p < 0.05) compared with the normothermic
      control group (86.6 +/- 20.7 mm3). In conclusion, the present study demonstrates
      that hypothermia is a potent neuroprotective method and an inhibition of the
      glutamate excitotoxic process may contribute the protective mechanisms of
      hypothermia in this rat acute SDH model.

PMID- 11450085
TI  - Blockade of histamine H2 receptors attenuate blood-brain barrier permeability,
      cerebral blood flow disturbances, edema formation and cell reactions following
      hyperthermic brain injury in the rat.
AB  - Role of histamine H2 receptors in blood-brain barrier (BBB) disturbances,
      cerebral blood flow (CBF), brain edema formation, and cell injury caused by heat
      stress in a rat model was examined using the pharmacological approach. Blockade
      of histamine H2 receptors by cimetidine or ranitidine significantly attenuated
      the BBB permeability to Evans blue albumin and [131]I-sodium extravasation, brain
      edema formation and cell injury following 4 h heat stress in rats at 38 degrees
      C. These drug treatments also restored the CBF to near normal values. These
      beneficial effects in heat stress were most marked in rats treated with
      ranitidine compared to cimetidine given in identical dosage. Our observations
      suggest that blockade of histamine H2 receptor is beneficial in hyperthermic
      brain injury and indicates that histamine is involved in the pathophysiology of
      heat stress induced brain dysfunction. Our study strongly suggests further need
      to develop more specific and sensitive histaminergic H2 receptor blockers for the
      treatment of neurological ailments.

PMID- 11450086
TI  - Selective alteration of calcitonin gene related peptide in hyperthermic brain
      injury. An experimental study in the rat brain using immunohistochemistry.
AB  - The possibility that calcitonin gene related peptide (CGRP) participates in the
      pathophysiology of hyperthermic brain injury was examined in a rat model. The
      CGRP immunoreactivity was examined in several brain regions of control and 4 h
      heat stressed rats using immunohistochemistry. Subjection of animals to heat
      stress in a biological oxygen demand (BOD) incubator at 38 degrees C for 4 h
      resulted in a marked redistribution of CGRP immunoreactivity. Thus, in cerebral
      cortex, hippocampus, cerebellum, medulla and spinal cord the CGRP
      immunoreactivity was profoundly increased following heat stress. On the other
      hand in brain stem and pons, the CGRP activity is downregulated. These
      observations suggest that heat stress has the capacity to influence CGRP
      immunoreactivity and this redistribution of the peptide is somehow associated
      with the molecular mechanisms of thermal information processing system of the CNS
      in heat stress, not reported earlier.

PMID- 11450087
TI  - Protective effect of mild hypothermia on symptomatic vasospasm: a preliminary
      report.
AB  - Mild hypothermia (32-34 degrees C of brain temperature) was used for brain
      protection in patients with progressive ischemic neurological deficits associated
      with severe cerebral vasospasm and who did not respond to medical treatment or
      intravascular angioplasty. Results showed that 2 of 3 patients in Hunt & Kosnik
      grade I to III and 2 patients who underwent delayed operation on day 5 and 9 each
      and had ischemic neurological deficits made good recovery with this treatment.
      Favourable outcome was obtained in 4 of 9 patients in grade IV and V. Mild
      hypothermia is thought to provide brain protection in critical ischemia due to
      severe cerebral vasospasm and can lengthen therapeutic time to employ angioplasty
      and intraarterial Papaverin infusion.

PMID- 11450088
TI  - The selectin superfamily: the role of selectin adhesion molecules in delayed
      cerebral ischaemia after aneurysmal subarachnoid haemorrhage.
AB  - Cerebral ischaemia and reperfusion injury may be exacerbated by leukocyte
      recruitment and activation. Adhesion molecules play a pivotal role in leukocyte
      recruitment. We report a prospective study of the potential role of the selectin
      family of adhesion molecules (E-, P- and L-selectin) in delayed cerebral
      ischaemia (DID) following aneurysmal subarachnoid haemorrhage. In patients with
      good grade SAH, we have compared serum concentrations of E-, P- and L-selectin,
      between patients who do, and do not develop delayed cerebral ischaemia. There was
      no difference in E-selectin concentration between the two groups (44.0 ng/ml vs.
      37.4 ng/ml). Serum P-selectin concentration was significantly higher in patients
      with DID compared to those patients without DID (149.5 ng/ml vs. 112.9 ng/ml, p =
      0.039). Serum L-selectin concentrations were significantly lower in patients with
      DID (633.8 ng/ml vs 897.9 ng/ml, p = 0.013). We conclude that P- and L-selectin
      are involved in the pathogenesis of DID following aneurysmal subarachnoid
      haemorrhage. The results of this study do not elucidate the exact role of each
      selectin in DID.

PMID- 11450089
TI  - Influence of hypothermia on cell volume and cytotoxic swelling of glial cells in
      vitro.
AB  - In view of the increasing significance of mild hypothermia (32 degrees C) as an
      efficient procedure of neuroprotection, the present study was performed to
      examine the influence of this level of hypothermia on the volume of glial cells
      under physiological as well as under pathological conditions. The influence of
      mild (32 degrees C) and moderate (27 degrees C) hypothermia on cell volume and
      cell viability of C6 glioma cells was studied for 60 minutes in vitro. Cells were
      suspended in an incubation chamber under continuous control of temperature, pH
      and pO2. Cell volume was measured by an advanced Coulter system. Hypothermia
      itself was causing significant cell swelling in a dose-dependent manner, which
      could be prevented by omission of Na(+)-ions from the suspension medium, while
      the replacement of Cl(-)-ions failed to prevent cell swelling from hypothermia.
      Inhibition of the Na+/H(+)-antiporter with EIPA (5N-ethyl-n-isopropyl-amiloride,
      50 microM) was significantly reducing the hypothermia induced cell swelling,
      indicating activation of the Na+/H(+)-antiporter. Conversely, mild or moderate
      hypothermia failed to prevent cell swelling from lactic acid, arachidonic acid or
      glutamate, i.e. agents which are mediating the development of cytotoxic brain
      edema in vivo in cerebral trauma, ischemia and other acute insults. The findings
      indicate that cerebral protection by hypothermia in vivo is most likely not
      attributable to an inhibition of cytotoxic brain edema. Further investigations,
      however, are required in vivo and in vitro to elucidate the hypothermia-induced
      swelling of glial cells in more detail, e.g. as to the role of the Na+/H(+)
      antiporter.

PMID- 11450090
TI  - Clinical experiences with the dual-switch valve in patients with normal pressure
      hydrocephalus.
AB  - In patients with normal pressure hydrocephalus (NPH) we compared the
      postoperative results reference to the implanted valve type. In 117 patients
      diagnosed with normal pressure hydrocephalus there was placement of 47 Cordis
      Standard valves (CSV), 20 Cordis Orbis Sigma valves type I (OSV) and 50 Miethke
      Dual-switch valves (DSV). Ninety-five patients (36/19/40) were re-evaluated.
      Normal pressure hydrocephalus was graduated according to the results of the
      intrathecal infusion test in an early and late stage. There were no statistical
      differences in mechanical and infective complications between the different valve
      types. We found significant differences in overdrainages and subdural hematomas.
      Two patients (6%) with a CSV, 3 patients (16%) with an OSV and 1 patient (3%)
      with a DSV developed clinical symptoms due to this. The course of disease in
      patients with NPH is influenced by the stage of disease--degree of cerebral
      atrophy--and also by the implanted valve type. The great amount of overdrainage
      complications and subdural hematomas in the Cordis Orbis Sigma valve group may be
      an argument against this valve. Our clinical experiences with the Miethke Dual
      switch valve show that this hydrostatic valve may be advantageous for patients
      with NPH.

PMID- 11450091
TI  - Endoscopic ventriculostomy versus shunt operation in normal pressure
      hydrocephalus: diagnostics and indication.
AB  - In contrast to shunt operation the indication for an endoscopic ventriculostomy
      in patients diagnosed for normal pressure hydrocephalus is not scientifically
      established. From September 1997 to March 1999 we operated on 36 patients
      diagnosed for normal pressure hydrocephalus. Diagnosis was established by means
      of the intrathecal lumbar or ventricular infusion test, the cerebrospinal fluid
      tap test and MRI-CSF flow studies pre- and post-operatively. In 30 patients (83%)
      we implanted a ventriculo-peritoneal shunt, and in 6 patients (17%) we performed
      the endoscopic assisted third ventriculostomy. With our created NPH recovery rate
      and use of the clinical grading for normal pressure hydrocephalus created by
      Kiefer and Steudel we compared the operative results of both patient groups. In
      patients with a pathologically increased resistance to CSF outflow in the lumbar
      infusion test a shunt implantation is indicated. Patients whose outflow
      resistance is increased in the ventricular infusion test but with a physiological
      lumbar infusion test are suspected for a functional aqueduct stenosis and should
      be treated by means of an endoscopic assisted ventriculostomy.

PMID- 11450092
TI  - Traumatic brain injury in mice deficient in poly-ADP(ribose) polymerase: a
      preliminary report.
AB  - Poly (ADP-ribose) polymerase (PARP) is a ubiquitous nuclear enzyme that, when
      activated by free-radical induced DNA damage, contributes to energy failure and
      cell death in models of central nervous system ischemia and reperfusion. PARP
      contributes to neuronal cell death in vivo after cerebral ischemia/reperfusion,
      however, the role of PARP in the pathogenesis of traumatic brain injury (TBI) is
      unknown. We hypothesized that, compared to wild type mice (+/+), mice deficient
      in PARP (-/-) would have reduced motor and cognitive deficits after TBI. Mice
      underwent controlled cortical impact (CCI) (6 m/s, 1.2 mm depth) and were tested
      for motor (d 1-5) and cognitive (d 14-18) function after CCI. PARP -/- mice
      demonstrated improved motor performance and improved cognitive function after CCI
      (both p < 0.05 compared to +/+). This is the first study to evaluate a role for
      PARP in functional outcome after TBI. The results suggest a detrimental role for
      PARP in the pathogenesis of TBI.

PMID- 11450093
TI  - Increased immunolocalization of nitric oxide synthases during blood-brain barrier
      breakdown and cerebral edema.
AB  - The role of nitric oxide (NO) in blood-brain barrier (BBB) breakdown and edema
      formation was investigated in the rat cortical cold injury model over a period of
      10 min to 6 days post cold-injury by immunolocalization of fibronectin as a
      marker of BBB permeability alterations and endothelial (e) and inducible (i)
      nitric oxide synthases (NOS), which are markers of NO biosynthetic activity. BBB
      breakdown to fibronectin in lesion vessels was observed at 10 minutes post
      injury, was maximal between 60 minutes and 3 hours and declined gradually
      thereafter, while perilesional vessels remained permeable up to 5 days. Increased
      eNOS immunoreactivity was observed in endothelium of perilesional permeable
      vessels starting at 12 hrs and was maximal between 4-6 days, after which
      immunoreactivity decreased reaching basal levels by 5-6 days. Immunoreactivity
      for iNOS was absent in normal brain and was first observed in polymorphonuclear
      leukocytes and endothelium of lesion vessels at 3 hrs. Maximal iNOS
      immunoreactivity was observed in endothelial cells and macrophages during the
      period of angiogenesis. Smooth muscle cells of overlying hyperplastic pial
      vessels showed iNOS immunoreactivity up to 6 days. The demonstration of increased
      NO synthases at the lesion site during BBB breakdown and edema formation and
      angiogenesis suggests that NO plays a role in these processes.

PMID- 11450094
TI  - Biological functions of extravasated serum IgG in rat brain.
AB  - During blood-brain barrier opening serum IgG could be extravasated. The function
      of intraparenchymal IgG, however, is unknown. Its biological effects in the acute
      phase were currently investigated. From rat autoserum IgG was purified and
      injected into the cortex. Similarly, IgG-Fab fragment was prepared and
      administered likewise. As for the control group, only vehicle was injected.
      Animals were sacrificed on days 1, 2 and 4 after the infusion and were
      histologically evaluated. On days 1 and 2, the infusion of IgG caused significant
      intraparenchymal infiltration of neutrophils which expressed LFA-1-alpha. It also
      induced CR3 up-regulation in microglia and endothelial ICAM-1 expression. On day
      4, these findings had disappeared. HE stained brain sections and the TUNEL method
      did not reveal significant nerve cell death in IgG injected animals during the
      experiment as compared to the controls. IgG-Fab did not cause significant changes
      either. Extravasated IgG has been viewed to have biochemical functions. Its Fc
      fragment seemed to cause microglial and endothelial activation, followed by
      leukocytic infiltration. This sequence itself was not neurotoxic. Therefore, it
      is suggested that extravasated IgG is one of the inducers that modulate cellular
      responses in the acute phase of brain damage.

PMID- 11450095
TI  - Possible reverse transport of beta-amyloid peptide across the blood-brain
      barrier.
AB  - Our experiments were performed to test the hypothesis that human beta-amyloid
      peptide 42 (beta A) is able to enter and exit the brain parenchyma through the
      blood-brain barrier. In an effort to determine the effect of beta A in an animal
      model, we have injected beta A i.v. into rats following single and repeated brain
      ischemia. Rats were sacrificed at 3 and 12 months after injection and beta A was
      localized by monoclonal antibody (mAb) 4G8. The present observations revealed an
      abundant presence of beta A in the extracellular space of the brain, which
      appeared to be dilated, and a vigorous uptake of beta A into the cytoplasm of
      endothelial and ependymal cells, pericytes, astrocytes and neurons. Some of the
      beta A deposits were associated and/or had migrated to the vessels and to the
      ventricles, and by 3 months a significant amount of beta A was directly
      associated with the vessels and was observed inside the ventricular space.
      Virtually no soluble and aggregating beta A was found in brain tissue 1 year
      later. This suggests that phagocytic pericytes and astrocytes take up exogenous
      beta A in an attempt to clear the peptide from the brain extracellular space and
      deliver it to the circulation. Further, direct removal of beta A from the
      ventricles by the bloodstream is also possible. These observations suggest that a
      reverse transport of beta A across endothelial cells of microvessels represents
      one of the possible mechanisms responsible for removal of extravasated beta A.
      The findings of the present study indicate that in normal conditions beta A is
      rapidly cleared from the cerebrospinal fluid and brain parenchyma, suggesting
      that irreversible changes in the physico-chemical properties of the
      cerebrovascular endothelial cell surface are involved in beta A deposition in the
      brain in Alzheimer's disease (AD).

PMID- 11450096
TI  - Reducing conditions produce a loss of neuroprotective efficacy of competitive but
      not non-competitive antagonists in a model of NMDA-mediated excitotoxicity in
      organotypic hippocampal slice cultures.
AB  - Experimental data indicate that NMDA receptor activation is strongly implicated
      in the pathogenesis of cerebral ischaemia. However, the results from in vivo
      studies are equivocal, with NMDA antagonists being active in only some models. It
      has recently been demonstrated that competitive and non-competitive NMDA
      antagonists behave differently under normal and ischaemic conditions. These
      studies have used organotypic hippocampal slice cultures to investigate whether
      this disparity is due to redox-modulation of the NMDA receptor which occurs in
      ischaemia. NMDA-mediated toxicity was concentration dependent with little damage
      occurring with less than 10 microM NMDA and maximal damage produced by 30 microM.
      NMDA toxicity was significantly enhanced by pre-treatment with 1 mM
      dithiothreitol, a reducing agent, such that damage occurred at 1 nM NMDA, and
      maximal damage was produced by 10 microM. The efficacy of MK-801 was not altered
      by reducing conditions, but the EC50 of the competitive antagonist APV was
      increased by 20-fold. These data strongly suggest that the neuroprotective
      efficacy of NMDA antagonists is significantly altered under ischaemic conditions,
      and that more beneficial effects will be obtained with antagonists having a
      higher affinity for the receptor in the reduced configuration.

PMID- 11450097
TI  - Role of nitric oxide in blood-brain barrier permeability, brain edema and cell
      damage following hyperthermic brain injury. An experimental study using EGB-761
      and Gingkolide B pretreatment in the rat.
AB  - The role of oxidative stress in hyperthermia induced upregulation of constitutive
      and inducible isoforms of nitric oxide synthase (NOS) in the central nervous
      system (CNS) was investigated using immunohistochemistry in a rat model. Exposure
      of rats to heat stress at 38 degrees C for 4 h resulted in marked upregulation of
      constitutive NOS (cNOS) and a mild but significant expression of inducible NOS
      (iNOS) in several brain regions exhibiting leakage of the blood-brain barrier
      (BBB), brain edema formation and cell injury. Pretreatment with the potent
      antioxidative compound EGB-761 or its constituent, Ginkgolide B significantly
      attenuated upregulation of cNOS and iNOS in the brain and also reduced the BBB
      permeability disturbances, brain edema and cell injury. These neuroprotective
      effects were most marked in the EGB-761 pretreated rats. Our observations
      strongly suggest that (i) EGB-761 and Ginkgolide B pretreatment offer significant
      neuroprotection in hyperthermic brain injury, (ii) upregulation of cNOS and iNOS
      are injurious to the cell and, (iii) oxidative stress plays an important role in
      NOS expression and cell injury.

PMID- 11450098
TI  - Extracts of Ginkgo biloba and Panax ginseng protect brain proteins from free
      radical induced oxidative damage in vitro.
AB  - Oxidative damage to normal human brain tissue was induced following exposure to
      hydroxyl (OH.) or superoxide (O2-.) free radical species generated by CO60
      irradiation in vitro. Both enzymic and cytoskeletal proteins showed substantial
      (dose dependent) oxidative damage following exposure to OH. or O2-., as
      quantified by SDS-polyacrylamide gel electrophoretic analysis. Extracts of Ginkgo
      biloba or Panax ginseng showed a remarkable capacity to protect brain tissue
      proteins from oxidative damage in vitro, even at extreme (2000 kRads) dosage
      levels of OH. or O2-.. We suggest, therefore, that the beneficial effect of these
      plant extracts in preventing brain tissue damage in vivo (e.g. following ischemia
      reperfusion) may result from their action in protecting brain proteins from
      oxidative damage, in addition to their previously reported capacity to reduce
      free radical induced lipid peroxidation.

PMID- 11450099
TI  - Heterogeneous mechanisms of early edema formation in cerebral contusion:
      diffusion MRI and ADC mapping study.
AB  - Severe cerebral contusion is sometimes associated with early edema formation
      within 24-48 hours post-trauma, and this frequently results in progressive ICP
      elevation and clinical deterioration. To investigate the underlying mechanisms of
      such severe contusion edema, diffusion imaging and ADC mapping were performed in
      20 patients with cerebral contusion, employing 1.5 T echo planar MRI. Within 24
      hours post-trauma, the diffusion images demonstrated a low intensity core in the
      central area and a high intensity rim in the peripheral area of contusion. The
      ADC value increased in the central area (ADC ratio (contusion/normal brain) =
      1.13 +/- 0.13) and decreased in the peripheral area (ADC ratio = 0.83 +/- 0.13).
      This suggested that intra- and extracellular components underwent disintegration
      and homogenization within the central area, whereas cellular swelling was
      predominant in the peripheral area. A crescent-shaped zone of very high ADC value
      (ADC ratio = 1.38-1.61) was observed at the border between these two areas during
      the period of 24-48 hours post-trauma in some cases, apparently indicating that
      edema fluid was accumulated within a space formed by homogenization. The ADC
      values in the peripheral area shifted to an increase after 48-72 hours post
      trauma. These findings imply that multiple mechanisms operate in early edema
      formation in cerebral contusion. It appears that the capacity for edema fluid
      accumulation increases in the central area and resistance for edema fluid
      propagation is elevated by cellular swelling in the peripheral area. We suggest
      that a combination of such events facilitates edema fluid accumulation in the
      central area and contributes, together with the cellular swelling in the
      peripheral area, to the mass effect of contusion edema. Diffusion MRI and ADC
      mapping represent powerful tools for investigating spatially as well as
      temporally heterogeneous mechanisms of contusion edema.

PMID- 11450100
TI  - p-Chlorophenylalanine, an inhibitor of serotonin synthesis reduces blood-brain
      barrier permeability, cerebral blood flow, edema formation and cell injury
      following trauma to the rat brain.
AB  - The role of serotonin in trauma induced alterations in blood-brain barrier (BBB)
      permeability, cerebral blood flow (CBF), brain edema and cell changes were
      examined in a new model of cortical injury in the rat using a pharmacological
      approach. A longitudinal incision into the right parietal cerebral cortex (about
      3 mm deep and 5 mm long) was associated with a profound increase in the BBB
      permeability to Evans blue and [131]I-sodium, brain water content, and a
      reduction in the CBF in both the ipsilateral and contralateral hemispheres 5 h
      after trauma. Nissl staining showed a profound nerve cell reaction in the
      parietal cerebral cortex of both hemispheres. The intensity of these pathological
      changes was most pronounced in the traumatised hemisphere. Pretreatment with p
      CPA, a serotonin synthesis inhibitor, significantly attenuated breakdown of the
      BBB permeability, brain edema and the CBF disturbances. Damaged and distorted
      nerve cells were markedly less frequent in p-CPA treated rats. This effect of the
      drug was most pronounced in the contralateral hemisphere. The observations
      strongly suggest that serotonin is one of the important neurochemical mediators
      of BBB permeability disturbances and brain edema formation in the trauma induced
      brain damage.

PMID- 11450101
TI  - S-100 serum levels and outcome after severe head injury.
AB  - S-100B a protein of astroglial cells is described as a marker for neuronal
      damage. Reliable outcome prediction from severe head injury is still unresolved.
      Clinical scores like the Glasgow Coma Score (GCS) and diagnostic scores like the
      Marshall CT Classification (MCTC) are well established and investigated, but
      there are still some concerns about these tools. The aim of this study was to
      investigate the predictive value of the initial serum level of S-100B. 44
      patients with severe head injury (GCS < 9) were included. Blood samples were
      drawn within 1 to 6 hours of injury. After a period of 11 months their outcome
      was correlated using the Glasgow Outcome Scale. Patients with good outcome had
      significantly lower serum concentrations of S-100 on admission (0.96 microgram/l
      versus 5.5 micrograms/l mean, p < 0.0001). In addition patients with a S-100
      serum level below 2 micrograms/l showed a significant better rating on the GOS at
      follow-up (4 points versus 1.8 points mean, p < 0.0001). With this cut-off line
      it was possible to predict longterm outcome with a sensitivity of 75% and
      specitivity of 82%. The serum level of S-100B calculated with one to six hours of
      a severe head injury is a useful additional outcome predictor.

PMID- 11450102
TI  - Case of the month. Mental triage.

PMID- 11450103
TI  - Mastering the Internet. Tips for spacing your Web site development.

PMID- 11450104
TI  - EMS Web world. Browsers, search engines & cool sites to speed you along the
      Internet highway.

PMID- 11450105
TI  - Helmet hazards. Do's & don'ts of football helmet removal.
AB  - EMS providers must use extreme caution when evaluating and treating an
      unconscious football player, especially when the extent of the injury remains
      unknown. Suspect any unconscious football player has an accompanying spinal
      injury until proven otherwise. If the football player isn't breathing or the
      possibility of respiratory arrest exists, it's essential that certified athletic
      trainers and EMS providers work quickly and effectively to remove the face mask
      and administer care. In most situations, the helmet doesn't need to be removed in
      the field. Proper management of head and neck injuries includes leaving the
      helmet in place whenever possible, removing only the face mask from the helmet
      and developing a plan to manage head- and neck-injured football players using
      well-trained sports medicine and EMS providers. EMS agencies should work with
      their local high school or college athletic trainers to practice these removal
      techniques prior to the start of the football season.

PMID- 11450106
TI  - Kidney complications. Examining the disease process & prehospital management of
      patients with ESRD.

PMID- 11450107
TI  - The regulation of pap and type 1 fimbriation in Escherichia coli.
AB  - The ability of bacterial pathogens to bind to the host mucosa is a critical step
      in the pathogenesis of many bacterial infections and, for Escherichia coli, a
      large number of different fimbrial adhesins have been implicated as virulence
      factors. In this chapter, our current understanding of the regulatory mechanisms
      that control the expression of two of the best characterized fimbrial adhesins,
      pyelonephritis-associated pilus (encoded by pap) and the type 1 fimbria (encoded
      by fim), will be described. The expression of both fimbrial adhesins is
      controlled by phase variation (the reversible and apparently random switching
      between expressing ('on') and non-expressing ('off') states), and is regulated in
      response to environmental conditions. The phase variation of pap (and of some
      other fimbriae in Escherichia coli) is determined by the formation of alternative
      nucleoprotein complexes that either activate (phase 'on') or suppress (phase
      'off') transcription of the fimbria genes. Formation of each complex protects a
      single Dam methylation site (5' GATC) from modification (GATCdist in phase 'on'
      cells and GATCprox in phase 'off' cells). Furthermore, complex formation is
      inhibited by methylation of the two 5' GATC sites. Both the phase variation of
      pap and the transcription of the pap genes in phase 'on' cells, are regulated and
      expression is subject to both positive and negative feedback control. In contrast
      to pap, the phase variation of fim is determined by the site-specific inversion
      of a short element of DNA (the fim switch). In phase 'on' cells, a promoter
      within the invertible element directs the transcription of the fim structural
      genes, whereas in phase 'off' cells transcription of the fimbrial genes is
      silenced. Despite the very different molecular mechanisms controlling the
      expression of pap and fim, the two systems share many features in common and have
      probably evolved to fulfill the same function. In addition to details about the
      molecular mechanisms that control pap and fim, the possible physiological
      significance of the observed regulation will be discussed.

PMID- 11450108
TI  - Metals and the rhizobial-legume symbiosis--uptake, utilization and signalling.
AB  - In this review, we consider how the nitrogen-fixing root nodule bacteria, the
      'rhizobia', acquire various metals, paying particular attention to the uptake of
      iron. We also review the literature pertaining to the roles of molybdenum and
      nickel in the symbiosis with legumes. We highlight some gaps in our knowledge,
      for example the lack of information on how rhizobia acquire molybdenum. We
      examine the means whereby different metals affect rhizobial physiology and the
      role of metals as signals for gene regulation. We describe the ways in which
      genetics has shown (or not) if, and how, particular metal uptake and/or metal
      mediated signalling pathways are required for the symbiotic interaction with
      legumes.

PMID- 11450109
TI  - The superfamily of chemotaxis transducers: from physiology to genomics and back.
AB  - Chemotaxis transducers are specialized receptors that microorganisms use in order
      to sense the environment in directing their motility to favorable niches. The
      Escherichia coli transducers are models for studying the sensory and signaling
      events at the molecular level. Extensive studies in other organisms and the
      arrival of genomics has resulted in the accumulation of sequences of many
      transducer genes, but they are not fully understood. In silico analysis provides
      some assistance in classification of various transducers from different species
      and in predicting their function. All transducers contain two structural modules:
      a conserved C-terminal multidomain module, which is a signature element of the
      transducer superfamily, and a variable N-terminal module, which is responsible
      for the diversity within the superfamily. These structural modules have two
      distinct functions: the conserved C-terminal module is involved in signaling and
      adaptation, and the N-terminal module is involved in sensing various stimuli.
      Both C-terminal and N-terminal modules appear to be mobile genetic elements and
      subjects of duplication and lateral transfer. Although chemotaxis transducers are
      found exclusively in prokaryotic organisms that have some type of motility
      (flagellar, gliding or pili-based), several types of domains that are found in
      their N-terminal modules are also present in signal transduction proteins from
      eukaryotes, including humans. This indicates that basic principles of sensory
      transduction are conserved throughout the phylogenetic tree and that the
      chemotaxis transducer superfamily is a valuable source of novel sensory elements
      yet to be discovered.

PMID- 11450110
TI  - Quorum sensing as a population-density-dependent determinant of bacterial
      physiology.
AB  - The discovery that bacterial cells can communicate with each other has led to the
      realization that bacteria are capable of exhibiting much more complex patterns of
      co-operative behaviour than would be expected for simple unicellular
      microorganisms. Now generically termed 'quorum sensing', bacterial cell-to-cell
      communication enables a bacterial population to mount a unified response that is
      advantageous to its survival by improving access to complex nutrients or
      environmental niches, collective defence against other competitive microorganisms
      or eukaryotic host defence mechanisms and optimization of population survival by
      differentiation into morphological forms better adapted to combating
      environmental threats. The principle of quorum sensing encompasses the production
      and release of signal molecules by bacterial cells within a population. Such
      molecules are released into the environment and, as cell numbers increase, so
      does the extracellular level of signal molecule, until the bacteria sense that a
      threshold has been reached and gene activation, or in some cases depression or
      repression, occurs via the activity of sensor-regulator systems. In this review,
      we will describe the biochemistry and molecular biology of a number of well
      characterized N-acylhomoserine lactone quorum sensing systems to illustrate how
      bacteria employ cell-to-cell signalling to adjust their physiology in accordance
      with the prevailing high-population-density environment.

PMID- 11450111
TI  - Flux analysis: a basic tool of microbial physiology.
AB  - Flux analysis (FA) is a means of organizing data to show flux through the central
      metabolic pathways (CMPs). It quantifies flux from uptake of carbon to the
      outputs of the CMPs, which are the precursors used for biosynthesis, acetate
      excretion and CO2. Fluxes to precursors reflect the commands of the genome and
      acetate excretion balances fluxes to precursor supply when uptake exceeds the
      capacity of the CMPs to allocate carbon in exactly the correct amount to each
      precursor. No other products have been detected in 11 phenotypes of Escherichia
      coli ML308. FA of each of these 11 phenotypes (with some additional variations in
      culture conditions, some selected mutations and one genetic construct) are shown
      as flux (mol (kg dry weight biomass)-1 h-1) and are the starting point for
      further exploration of the physiology of E. coli: FAs suggest the possibility of
      four strategies to reduce acetate excretion and these have been tested in two of
      the phenotypes (glucose and pyruvate). All are successful to some degree but
      results are not always what were expected. FA of such interventions suggest that
      some 'global' control mechanisms operate in E. coli ML308 independent of carbon
      source. There is a division in the CMPs between those pathways that use
      phosphorylated intermediates and those that do not and these, in turn, are
      divided into the Krebs cycle and the C2 and C3 monocarboxylic acids. Altogether,
      there are four 'compartments' and each contains intermediates that are also
      precursors.

PMID- 11450112
TI  - Nitrate reduction in the periplasm of gram-negative bacteria.
AB  - In contrast to the bacterial assimilatory and membrane-associated, respiratory
      nitrate reductases that have been studied for many years, it is only recently
      that periplasmic nitrate reductases have attracted growing interest. Recent
      research has shown that these soluble proteins are widely distributed, but vary
      greatly between species. All of those so far studied include four essential
      components: the periplasmic molybdoprotein, NapA, which is associated with a
      small, di-haem cytochrome, NapB; a putative quinol oxidase, NapC; and a possible
      pathway-specific chaperone, NapD. At least five other components have been found
      in different species. Other variations between species include the location of
      the nap genes on chromosomal or extrachromosomal DNA, and the environmental
      factors that regulate their expression. Despite the relatively small number of
      bacteria so far screened, striking correlations are beginning to emerge between
      the organization of the nap genes, the physiology of the host, the conditions
      under which the nap genes are expressed, and even the fate of nitrite, the
      product of Nap activity. Evidence is emerging that Nap fulfills a novel role in
      nitrate scavenging by some pathogenic bacteria.

PMID- 11450113
TI  - [Isolated atrophy of the infraspinatus muscle in baseball players].
AB  - Atrophy of infraspinatus muscle caused by suprascapular nerve entrapment is a
      typical disease of overhead sports such as volleyball, baseball and javelin. The
      chronic distress of suprascapular nerve infraspinatus branch may derive from
      nerve kinking and friction caused by an entrapment at the spino-glenoid notch,
      often repeated during external-rotation and abduction of shoulder. From 1999 to
      2000 4 athletes, out of 143 professional baseball players, were found suffering
      from this disease. The diagnosis was confirmed by MNR and EMG, while a isokinetic
      test quantified a loss of strength in external-rotation and allowed a standard
      parameter for the treatment result evaluation. The 4 athletes were submitted to a
      non-invasive rehabilitation protocol, thanks to electrostimulation and isokinetic
      exercises, aiming at strengthening the extrarotator muscles and restoring a
      suited musclar balance. A subjective improvement was verified and confirmed by
      isokinetic test in all the players; moreover no surgery was needed.

PMID- 11450114
TI  - Angiosarcoma of the spleen mimicking rupture. Case report and literature review.
AB  - Primary angiosarcoma of the spleen is very rare and only 143 cases have
      previously been reported. The pathogenesis is unknown. The clinical aspects are
      variable, but loss of weight, anaemia, splenomegaly and liver metastases are
      frequently present. The age range is generally 18 to 93 years; only four of the
      reported patients were under 20 (Chen KTK). The prognosis is very poor in any
      case and survival isn't more than two years: wherever the spleen undergoes
      spontaneous rupture the survival should be less than six months. Patients with or
      without metastatic disease may be treated by chemotherapy but with poor results.
      Radiotherapy is used for the pain from bone metastasis. We report the clinical
      case concerning a 79-years-old man with liver metastases and a 5-cm lesion in the
      spleen, where a subcapsular rupture was suspected.

PMID- 11450115
TI  - [Total arterial myocardial revascularization: surgical technique and mid-term
      results].
AB  - The purpose of this study is to evaluate perioperative and mid-term results of
      total arterial coronary revascularization in our experience and to establish its
      safety. One-hundred and ninety-one patients underwent total arterial coronary
      revascularization at our Institution from February 1997 to August 2000. The mean
      age was 60.1 years. Of the patients, 45% had three coronary vessels disease, 12%
      a left main coronary artery disease and 2.6% of them were classified urgent. Mean
      ejection fraction was 59.6%. Three hundred and thirty-four comprehensive
      anastomoses were performed; mean grafts per patient was 1.8. A Y or T graft with
      the left internal thoracic artery was used in 21 patients. The in-hospital
      mortality rate was 1% (2 patients). Complications included low cardiac output
      syndrome in 2.8% of patients, acute myocardial infarction in 0.9% and acute renal
      insufficiency in 3.1%. Intraaortic balloon pump was used in 1.8% of patients. At
      a mean follow-up of 899 days the first 81 patients contacted are all free of
      angina but two (one experienced an acute myocardial infarction and another one
      died for a pulmonary neoplasia). We conclude that total arterial coronary
      revascularization is a safe surgical technique, providing excellent perioperative
      and mid-term results.

PMID- 11450116
TI  - [Diagnosis and surgical treatment of primary hyperparathyroidism].
AB  - Primary hyperparathyroidism (HPP) is increasingly being recognized because of the
      widespread use of multiphasic screening for hypercalcemia, in patients without
      clinical signs. Each year develop 100,000 new cases in the United States,
      females/males 5:2; the peak of incidence is in V-VI degrees decade. We analyze
      our patients from November 1975 to July 2000. We have performed 112
      parathyroidectomy for HPP, 84 females and 28 males, median age 57.5 years. We
      have examined the surgical options, the value of PTH, calcium, and the number of
      pathological glands. The Authors discuss the invasive or non-invasive procedures
      and the surgical treatment.

PMID- 11450117
TI  - [Endoluminal repair of aortic aneurysms. Our experience].
AB  - From February 1998 and March 2000 fourteen patients underwent "custom made"
      aortic self-expanding endoprostheses implantation (World Medical Talent Sunrise):
      nine of them for dilative pathology of thoracic aorta and 5 for abdominal aortic
      aneurysm below renal arteries. The etiology was degenerative in 8 patients, false
      aneurysm in 2, chronic dissection in 2 cases, acute dissection in one patient and
      post traumatic in the last one. All patients underwent preoperative Computed
      Tomography and Substraction Angiography studies. Stent-graft implantation was
      successful in all cases but one who required the conversion of the endovascular
      procedure in traditional surgery for technical problems. There were no
      perioperative deaths or major complications. We registered 2 cases of dissection
      of the femoral artery used to introduce the stent-graft, and treated with an
      iliac-femoral prosthetic bypass. There were no cases of paraplegia or renal
      failure or bowel ischemia. With the exception of one patient, died for a car
      accident, the others are alive and continue their scheduled follow-up controls.
      Our experience shows that this procedure is safe, allowing favorable results, if
      compared to traditional surgery, even if it requires further long-term
      evaluations.

PMID- 11450118
TI  - [Experimental results of the use of hyaluronic acid based materials (CV Seprafilm
      and CV Sepracoat) in postoperative pericardial adhesions].
AB  - Repeat cardiac surgical procedures are associated with increased technical
      difficulty and risk related to the presence of dense adhesions between the heart
      and the surrounding tissues. We examined the efficacy of a bioabsorbable membrane
      containing hyaluronic acid in the prevention of pericardial adhesions in 23
      rabbits. After thoracotomy and pericardiotomy the animals were divided in three
      groups: Group 1 (9 animals) in which the epicardial surfaces were covered by
      Seprafilm membrane, Group 2 (9 animals) treated with both Seprafilm membrane and
      Sepracoat solution, and Group 3 (5 animals) as controls. The animals were
      reexplored at 10, 30 and 60 days: no intrapericardial adhesions were found in all
      the animals of Group 2. In 4 animals (44%) of Group 1 localized post-operative
      adhesions were detected, in absence of epicardial hyperplasia; in contrast, dense
      and diffuse adhesions were present in all the control animals. The use of the
      bioabsorbable membrane Seprafilm significantly reduces adhesion formation even if
      better results are possible with the previous intrapericardial administration of
      Sepracoat solution. Application of these biocompatible products could reduce the
      technical difficulty and risk of repeat surgical procedures.

PMID- 11450119
TI  - [Vertical transmission of HIV infection: risk factors and prevention strategies].
AB  - In this study it has been evaluated the connection between the maternal immune
      status and the obstetrical factors on the one hand end the perinatal transmission
      of HIV in the other as well as, the effects of zidovudine prophylaxis and
      elective caesarean section on vertical HIV transmission. From January 1987 to
      September 1999, 60 HIV infected pregnant women were followed with their 64
      infants. From July 1995 15 women and their respective children were treated with
      zidovudine prophylaxis (protocol ACTG 076); from June 1997, in 8 of these
      patients a systematic caesarean section was performed (7 electively and 1 on an
      emergent basis). The transmission rare was 20.5% among the 44 children in the
      group without zidovudine prophylaxis, compared with 7.1% among the 14 children in
      the group receiving Zidovudine. As for as the mother-child pairs receiving
      Zidovudine therapy, the rate of vertical transmission was 0% for the 7 mothers
      who underwent elective cesarean section and 14.3% for the 7 mothers with other
      ways of delivery. The interaction between zidovudine prophylaxis and elective
      caesarean section was associated with the lowest rate of vertical HIV
      transmission.

PMID- 11450120
TI  - [Buschke-Lowenstein tumor: report of 2 clinical cases].
AB  - In our department two cases of Buschke-Lowenstein tumor were up to day observed.
      The first case, a man 51 years old, showed a big exophytic growth all over the
      glans, plus some similar lesions all along the shaft of the penis, besides a
      bilateral inguinal lymphoadenopathy. The second case was that of a man 70 years
      old, presenting a single exophytic growth on the glans. Both cases underwent a
      surgical excision of the lesions. The first patient had a local relapse after one
      year and a second one after further four months, which were both surgically
      exsected. Today, both patients are disease-free, being elapsed twelve years and
      sixteen months respectively. Surgical excision seems therefore to answer well the
      clinical problem, as for as the rarity of distant spread, the feasibility of
      conservative removal or reiteration, should it the case, are concerned.

PMID- 11450121
TI  - [Interstitial laser therapy in benign prostatic hyperplasia].
AB  - The interstitial laser therapy is a low invasivity system for prostatic benign
      hyperplasia. We report our experience with Indigo 830e new system where diode
      laser and optical temperature sensor warrant a laser-induced interstitial thermal
      therapy able to continuously adjust energy delivery to the tissue.

PMID- 11450122
TI  - [Biopsy of sentinel lymph nodes in the treatment of breast carcinoma: experience
      of the Surgery Department of the Hospital of Parma].
AB  - Radical axillary nodes dissection in breast cancer is a standard for a correct
      staging, unfortunately this approach can cause several unpleasant sequelae and
      complications. Sentinel node biopsy applied to breast tumors could be a good
      option for predicting axillary nodes status avoiding complete dissection. The aim
      of this work is to report our experience with sentinel node biopsy during a
      period of 18 months. One hundred and nine patients with an infiltrating breast
      tumor T1 had been studied. There wasn't clinical and ultrasonographic evidence of
      axillary infiltration. Tumors had been injected on the day before surgery with a
      mixture of colloidal human albumin particles marked with 99m Technetium. In 108
      out of 109 patients (99%) sentinel node had been identified using a gamma probe
      and biopsied during surgical intervention performed under local anesthesia.
      Sentinel node has been examined both with conventional histology and
      immunohistochemistry. In 26 cases the node was positive for metastases. Radical
      axillary dissection in this subgroup of patients showed that in 85% of them
      sentinel node was the only positive. We conclude that sentinel node biopsy can be
      a good alternative to traditional axillary dissection but there are still
      important questions about the best method of analysis and, before the technique
      become a routine procedure in breast cancer management, we should know the
      results of prospective clinical trials comparing survival of patients staged by
      sentinel node biopsy versus traditional axillary dissection.

PMID- 11450123
TI  - [Infrared videonystagmography in vestibular diagnosis].
AB  - Vestibular examination relied upon electronystagmography (ENG) for more than 50
      years. This method is based on recording of nystagmus (Ny) without any
      possibility to see the ocular movements directly. More recently, infrared
      videonystagmography (VNG) entered the diagnostic protocol of vestibular
      disorders. VNG permits to record and visualize Ny, both in the darkness and with
      open eyes. Aim of the present study was to verify the possible advantages of VNG
      versus ENG for functional evaluation of the vestibular system in patients
      suffering from otoneurological disorders. To that purpose, VNG and ENG tracings
      were recorded in 12 patients. The preliminary results show that there are not
      significant differences in quantitative evaluation of Ny between the two methods.
      Anyhow, VNG has some technical and clinical advantages that make it the method of
      choice.

PMID- 11450124
TI  - [Gastric polyps: possible causes of pyloro-duodenal obstruction].
AB  - We reported three cases of transpyloric prolapsed polipoid lesions. Abdominal
      pain, early satiety are the most common presenting features. Endoscopies and
      polipectomy are important for a correct diagnostic evaluation. Large polyps (> 2
      cm), if prolapsed, can require a surgical excision.

PMID- 11450125
TI  - [Tridimensional (3D) reconstruction in the osteoarticular area].
AB  - Three-dimensional reconstruction techniques have been used since the development
      of computed tomography. In skeletal radiology they have been used to better
      visualize fractures and spatial relationships between fragments in maxillo-facial
      surgery. Aim of this paper is to illustrate the most important reconstruction
      techniques and their application in skeletal radiology. Images can be obtained by
      means of a Spiral CT scanner with the following parameters:
      collimation/pitch/reconstruction interval 2/1/1. Acquired images are sent to a
      workstation with a software running on a Window NT platform Vitrea 2.01 (Vital
      Images, USA) equipped with Volume Rendering algorithm. SSD as well as MPR and
      curved reformatted reconstruction algorithms is available at the CT console.
      Three-dimensional reconstruction have been shown to be useful for the diagnosis
      and for a preoperative planning. Other applications of three-dimensional
      reconstruction techniques are prosthesis engineering and biomechanic research. 3D
      images help the communication between radiologist and surgeons. Technical
      advances in acquisition methods and in reconstruction algorithms are needed to
      improve image quality and use in skeletal radiology.

PMID- 11450126
TI  - [Rotator cuff rupture. Diagnostic imaging].
AB  - Conventional radiography, ultrasound, Magnetic Resonance (MR), Arthrography
      Computed Tomography (Arthro-CT) and Arthrography Magnetic Resonance (Arthro-MR)
      are available for diagnosis of rotator cuff tears. Our purpose is to assess the
      specificity and sensitivity of these examinations and if they could give to the
      surgeon all the informations to select the more accurate treatment. We have
      evaluated retrospectively the images of 68 patients, 43 male and 25 female
      (average age 51 years), which then have been surgically treated for rotator cuff
      pathology. On the basis of our findings, we think that conventional radiography
      and ultrasound are excellent in a first evaluation. MR images, particularly in
      the coronal and sagittal oblique planes, are able to demonstrate partial or
      complete rotator cuff tears. The use of intra-articular contrast medium (arthro
      CT, arthro-MR) should be reserved for partial lesions on specific cases.

PMID- 11450127
TI  - [Shoulder instability: diagnostic imaging].
AB  - Shoulder instability is often diagnosed among athletes; two clinical forms are
      distinguished: anatomical instability, with recurrent luxation of the shoulder,
      and functional instability, with pain, articular "click" and sensation of
      instability. Lesions of periarticular soft tissues (capsula, fibrocartilaginous
      labrum, gleno-humeral ligaments and rotator cuff) are common in both forms, while
      lesions of bone structures (humeral head and glenoid of scapula) are typical of
      shoulder with previous dislocation. Purpose of our retrospective study was to
      verify the value of magnetic resonance (MRI) and computed arthrography (arthro
      CT) in diagnosing these lesions in 57 patients suffering from shoulder
      instability. On the basis of our results and experience we think that in a
      preoperative evaluation of an unstable shoulder, arthro-CT and arthro-MRI are
      more accurate because the intra-articular injection of a contrast medium better
      identifies lesions of capsula, gleno-humeral ligaments and fibrocartilaginous
      labrum. In other circumstances, such as the study of the shoulder for legal
      purposes, MRI is preferable because it offers an accurate and global evaluation
      of periarticular structures.

PMID- 11450128
TI  - [Shoulder diseases in throwing athletes: radiologic assessment and surgical
      correlation].
AB  - Lesions of the shoulder, especially rotator cuff tears and glenoid labrum (SLAP)
      lesions, are commonly caused by traumatic episodes in athletes such as repeated
      trauma from throwing. The available radiological methods are MRI, CT and MR
      arthrography. Twelve athletes suffering from shoulder pain or instability have
      been studied and then underwent successful treatment in arthroscopy. On the basis
      of our results and experience, we think that MR, especially with intra-articular
      injection of contrast medium, is the best examination because it offers an
      accurate evaluation of both rotator cuff and glenoid labrum. Nevertheless
      difficulties are often encountered and definitive diagnosis sometime rests on
      arthroscopic exploration.

PMID- 11450129
TI  - [Wrist trauma: diagnostic imaging].
AB  - Wrist injury is common throughout life and, although history and physical
      examination provide important information regarding the type of lesion, a
      radiological study is essential to determine a specific diagnosis. Conventional
      radiography plays a central role in the wrist injuries but the diffusion of more
      sensitive methodics offers new possibilities. Our purpose is to evaluate the role
      of computed tomography (CT), magnetic resonance (MR) and arthrography in wrist
      trauma. We retrospectively examined the images of 45 patients with wrist
      injuries: in every patients a radiological examination in 4 standard projections
      was executed while in 25, 9 and 11 patients CT,MR and arthrography were
      performed. On the basis of our findings we think that conventional radiography is
      often sufficient for diagnosis of bone lesions even if CT sometimes is required
      to detect subtle fractures. MR has an high sensitivity not only for abnormalities
      of soft tissues, including interosseous ligaments and triangular fibrocartilage,
      but also bony abnormalities such as occult fractures and early osteonecrosis.
      Arthrography still remains the best procedure for evaluating lesions of
      triangular fibrocartilage and intercarpal ligaments especially in a preoperative
      phase.

PMID- 11450130
TI  - [Injuries of the cruciate ligament of the knee: diagnostic contribution of MR and
      spiral CT].
AB  - Lesions of cruciate ligament are common after knee trauma of different degree of
      gravity. Lesions evaluation is possible thanks to CT and MRI. Our purpose is to
      verify their value in diagnosis of cruciate ligaments lesions. We retrospectively
      evaluated 160 patients (80 CT and 80 MRI) with subsequent diagnosis of cruciate
      ligaments injury. CT and MRI were performed in the acute phase and in the
      subacute phase within 2-3 weeks from trauma. On the basis of our results CT and
      MRI shown a reduced sensitivity in acute phase owing to the intraarticular
      haemorrhage; in this phase MRI gives more information about fibres interruption.
      In subacute or chronic phase, both methods are correct in recognising the lesions
      but MRI is more sensitive and accurate. It is a real wish that, with more MRI
      machines diffusion, this method will be preferred in the study of cruciate
      ligaments both in acute phase and subacute-chronic phase.

PMID- 11450131
TI  - [Meniscal injuries of the knee. Diagnostic imaging].
AB  - Nowadays, treatment of meniscal tears is conservative with removal only of the
      broken part of meniscus. For this reason, before arthroscopy, the orthopaedic
      surgeon needs for an accurate preoperative diagnosis that could be obtained with
      computed tomography (CT) and magnetic resonance (MR). Our purpose is to value the
      actual role of CT and MR in diagnosis of meniscal tears. We retrospectively
      evaluated CT and MR images of 128 patients (average age 32 years) who then
      underwent arthroscopy. On the basis of our findings CT and MR have been shown to
      be very accurate to detect meniscal tears, even if with both methodics false
      positives and false negatives are possible. Nevertheless, MR is able to give high
      resolution multiplanar images without using ionising radiations and is preferable
      because of its high accuracy in recognising associated lesions of ligaments or
      articular cartilage.

PMID- 11450132
TI  - [Femoro-patellar instability: radiologic assessment].
AB  - To propose a simple and reproducible radiological evaluation of the
      patellofemoral instability that enables the orthopaedic in choosing the best
      therapy. The radiographs and CT examinations of 55 patients, 38 female and 17
      male (range 18-32 years) have been evaluated retrospectively. Twenty-height of
      them underwent surgical treatment for patellar instability. A radiological
      protocol which includes conventional radiographs in two projections and a CT
      examination both in extension, with and without quadriceps contraction, and in
      flexion at 20 degrees allows to give all the informations one's need for
      evaluating patellar height and mobility, trochlear dysplasia, valgism of the knee
      and the degree of excessive lateral position of the anterior tibial tuberosity.
      It's a simple, quick, accurate and reproducible protocol to do, even with
      different radiological systems.

PMID- 11450133
TI  - [Spiral CT and MR in injuries of the ankle and the foot].
AB  - Conventional radiography is the first radiological examination in injuries of
      ankle and foot, but often it has normal findings or it is difficult to execute
      for critical conditions of patients. Our purpose was to assess the value of CT
      and MRI in injuries of ankle and foot; we retrospectively reviewed the MR and CT
      images from 48 patients (age range 18-55 years), whose 16 had a major trauma with
      other skeletal segment lesions and the remaining a minor trauma limited to ankle
      and foot. On the basis of our results and experience, we think that in major
      trauma CT and MRI have similar findings about preoperative evaluation of
      fractures even if MR better identifies ischemia of fragments, subcortical
      contusions and lesions of ligaments, capsula or tendons. In minor trauma, MR is
      superior to CT because it can diagnose lesions of bone and periarticular
      structures that are difficult or impossible to identify with other instrumental
      examinations.

PMID- 11450134
TI  - [Spiral CT in maxillo-facial trauma].
AB  - Fractures of facial skeleton are common in a busy emergency department in often
      requires careful radiological study before surgical treatment. Radiographic
      evaluation of facial injuries is especially challenging because the complex
      facial structure results in a confusing overlapping of densities on the
      radiograph. Instead Spiral-CT enables obtaining images on different planes so
      that even subtle or complex fractures may be evaluated in the best way. Moreover,
      associated lesions of important organs can be diagnosed. Our purpose is to verify
      the value of Spiral-CT in traumatology of facial skeleton. We have evaluated
      retrospectively the images of 82 patients admitted for facial trauma. On the
      basis of our findings we think that conventional radiography should be reserved
      only for light traumas of superficial structures (nose, zygomatic arch, body of
      jaw); in the remaining cases Spiral-CT should be the first radiological
      examination.

PMID- 11450135
TI  - [Cervical spine injuries: diagnostic imaging].
AB  - In past few years, traumas of cervical spine have increased, chiefly owing to
      rise of road accidents. Nevertheless, only in a small percentage of cases lesions
      of cervical spine occur and, in order to reduce many negative radiographs, a
      careful clinical examination is required. Our purpose is to verify the value of
      radiology in evaluation of acute trauma of cervical spine and to propose an
      adequate radiological protocol. In the course of two years (1998-99), 376
      patients were admitted in consequence of cervical trauma of different degree of
      gravity. In all patients, conventional radiographs were obtained, in 93 a
      computed tomography (CT) examination was executed and only in 18 patients with
      neurological symptoms a magnetic resonance (MR) was required. Fractures of
      cervical spine wee identified in 91 cases and in patients in which MR images were
      obtained, neurological lesions of various severity were diagnosed. On the basis
      of our results, we think that, in a clinical suspicion of cervical spine lesions,
      a conventional radiographic study has first to be performed even if often good
      radiographs aren't obtained for technical difficulties. If doubts persist on
      conventional radiographs or a fractures has already been diagnosed on radiographs
      but we want to verify its stability, a CT needs to be performed. MR is required
      if neurological symptoms are present in order to diagnose lesions of spinal
      marrow, nerve roots or ligaments.

PMID- 11450136
TI  - The 'lactate paradox', evidence for a transient change in the course of
      acclimatization to severe hypoxia in lowlanders.
AB  - The metabolic response to exercise at high altitude is different from that at sea
      level, depending on the altitude, the rate of ascent and duration of
      acclimatization. One apparent metabolic difference that was described in the
      1930s is the phenomenon referred to as the 'lactate paradox'. Acute exposure to
      hypoxia results in higher blood lactate accumulation at submaximal workloads
      compared with sea level, but peak blood lactate remain the same. Following
      continued exposure to hypoxia or altitude, blood lactate accumulation at
      submaximal work and peak blood lactate levels are paradoxically reduced compared
      with those at sea level. It has recently been shown, however, that, if the
      exposure to altitude is sufficiently long, blood lactate responses return to
      those seen at sea level or during acute hypoxia. Thus, to evaluate the 'lactate
      paradox' phenomenon in relation to time spent at altitude, five Danish lowland
      climbers were studied at sea level, during acute exposure to hypoxia (10% O2 in
      N2) and 1, 4 and 6 weeks after arrival in the basecamp of Mt Everest
      (approximately 5400 m, Nepal). Basecamp was reached after 10 days of gradual
      ascent from 2800 m. Peak blood lactate levels were similar at sea level (11.0 +/-
      0.7 mmol L-1) and during acute hypoxia (9.9 +/- 0.3 mmol L-1), but fell
      significantly after 1 week of acclimatization to 5400 m (5.6 +/- 0.5 mmol L-1) as
      predicted by the 'lactate paradox'. After 4 weeks of acclimatization, peak
      lactate accumulation (7.8 +/- 1.0 mmol L-1) was still lower compared with acute
      hypoxia but higher than that seen after 1 week of acclimatization. After 6 weeks
      of acclimatization, 2 days after return to basecamp after reaching the summit or
      south summit of Mt Everest, peak lactate levels (10.4 +/- 1.1 mmol L-1) were
      similar to those seen during acute hypoxia. Therefore, these results suggest that
      the 'lactate paradox' is a transient metabolic phenomenon that is reversed during
      a prolonged period of exposure to severe hypoxia of more than 6 weeks.

PMID- 11450137
TI  - [Analysis of gag gene subtypes of HIV-1 variants isolated in Russia by
      comparative assessment of heteroduplex electrophoretic mobility].
AB  - Using heteroduplex mobility assay modified for gag gene analysis (HMA-gag), 37
      HIV-1 samples previously genotyped by gag and env nucleotide sequencing were
      studied. It has been demonstrated that both sensitivity and specificity of HMA
      gag were 100%. The gag gene region derived from 20 env subtype A HIV-1 isolates
      was analyzed by this method. AG recombinant, representing a circulating
      recombinant form of HIV-1 (AGlbNG) was found among five HIV-1 strains isolated
      from patients infected through heterosexual contacts in Russia. No novel
      recombinant forms were found among fifteen HIV-1 variants infected from drug
      users in 7 cities of Russia. The proposed HMA-gag method extends the
      potentialities of investigating the genetic variability of HIV-1 and in
      combination with the previously proposed method for env gene is a convenient
      approach to search for recombinant forms of this virus.

PMID- 11450138
TI  - [Virus-specific proteins of Crimean-Congo hemorrhagic fever].
AB  - A variant of Asian strain Hodzha of Crimean-Congo hemorrhagic fever (Hodzha-A),
      adapted to Vero-E6 culture and yielding high harvest in it, was used for analysis
      of the synthesis of virus-specific proteins and protein composition of virions.
      Major virus-specific proteins with mol. weights 110, 83, 78, 55, 57, and 45 kD
      and minor low-molecular-weight proteins of 42, 36, 23, and 21 kD were detected by
      immunoprecipitation with hyperimmune ascitic fluid and polyacrylamide gel
      electrophoresis in infected cell lysates. N-type glycosylation of gp83 and gp78
      was shown using tunicamicin. Viral proteins with mol. weights of 83, 78, 55, 57,
      and 45 kD were detected in infected cell culture fluid and in purified virion
      preparations after ultracentrifugation in sucrose density gradient. Two proteins
      with mol. weights 55-57 and about 180 kD were detected in purified nucleocapside
      preparations.

PMID- 11450139
TI  - [Extracellular immunoreactive nucleoprotein of Influenza virus not related to the
      virion].
AB  - Extracellular immunoreactive virus NP is accumulated in virus-containing fluid in
      the course of A/Duck/Ukraine/1/63(H3N8) influenza virus infection. The major part
      of this extracellular NP is included in viral RNP and characterized by relatively
      low molecular weight: 53 kD vs. 56 kD of virion NP. Extracellular immunoreactive
      NP is oligomerized. Presumably, there is partially intracellular cleavage of NP
      with loss of hydrophobic determinants. Such truncated NP in RNP is highly
      hydrophilic and passes through cell membranes. These data prompt the diagnosis of
      influenza infection by detection of free immunoreactive NP in analyzed fluids.

PMID- 11450140
TI  - [Characteristics of humoral immunity to rubella virus in residents of Moscow in
      1998-1999].
AB  - A total of 400 blood samples were collected from residents of Moscow in 1998
      1999, 369 from adults aged mainly 19-31 years and from children aged 5-12 years.
      The mean incidence of antirubella antibody was 76.5%; the value varied in
      different age groups. The highest percentage of antibody detection was observed
      in men aged 19-25 years (91.8%) and the lowest in pregnant women aged 18-38 years
      (66-67%). Estimation of antihemagglutinin titers in international Units showed
      that antibody titer 1:40 and higher protected from infection; such titers were
      detected in 73.6% examinees. In pregnant women the level of immunological defense
      was very low (only 56%), which necessitates urgent vaccination of adolescent
      girls and young women. The results of EIA were compatible with the results of
      indirect hemagglutination test (IHAT), but EIA was much more sensitive in cases
      with low titers of IHAT.

PMID- 11450141
TI  - [Immunological status of patients with epidemic parotitis].
AB  - Immunosuppression was detected in six patients with parotitis. The proliferation
      of peripheral blood mononuclear cells, NK activity, and CD4/CD8 index decreased,
      while the production of tumor necrosis factor alpha and interleukin 1 beta
      increased on day 1 after clinical manifestation of mumps. The clinical diagnosis
      of mumps was confirmed by serological analysis of paired sera. Besides parotitis
      virus, herpes simplex type 1 virus was detected in two saliva samples by the
      polymerase chain reaction. Herpes (lip vesicles) manifested in these patients on
      days 8 and 11 after manifestation of parotitis.

PMID- 11450142
TI  - [Mechanisms of mice resistance to influenza virus A/AICHI/2/68 after preventive
      injection with polyprenols ].
AB  - Preventive effect in influenza can be attained by intramuscular injections of fir
      (Abies) polyprenols. One of 5 tested polyprenol preparations (No. 1), injected 2
      days before aerogenic infection with influenza virus, reliably protected mice
      from disease. Mice pretreated with polyprenol preparations or Hanks' solution did
      not differ by accumulation of interferon in the lungs One day after aerogenic
      infection. Three days after injection of polyprenol preparation No. 1 the weights
      of the spleen and thymus significantly decreased. One day after injection cell
      count in the bronchoalveolar tract of mice was almost 2-fold higher than in the
      control at the expense of lymphocytes and macrophages. After 3 days the relative
      and absolute counts of macrophages decreased and those of lymphocytes decreased
      significantly. Three days after injection macrophages were 2-fold more active in
      absorption of zymosan granules. Preparation No. 1 affected the production of
      superoxide anion radicals, whose production by all macrophages in the
      bronchoalveolar tract of mice was significantly higher on day 1 postinjection
      than on day 3 and higher than on days 1 and 3 after injection of preparation No.
      2.

PMID- 11450143
TI  - [Effect of fullerene C60-polyvinilpyrrolidone complexes on influenza virus
      reproduction].
AB  - The capacity of water-soluble complexes of fullerene C60-polyvinylpyrrolidone to
      inhibit the replication of influenza viruses was studied. In contrast to
      remantadine, these complexes inhibit the replication of both A and B viruses
      (including the remantadine-resistant strains). The complexes inhibit influenza
      virus replication at all stages of replication cycle.

PMID- 11450144
TI  - [Structure of over lapping region of ICP18.5 and gB genes of type 1 bovine
      herpesvirus strain TK-A].
AB  - Nucleotide sequence of DNA fragment coding 3'-terminal of ICO 18.5 gene that
      overlaps the regulatory region and 5'-terminal of open reading frame of gB gene
      of bovine herpesvirus (BHV-1, subtype 1.3), strain TK-A, was determined.
      Comparative analysis of the sequence with the corresponding DNA regions of BHV-1,
      subtype 1.1, equine herpesviruses of the first and fourth types, and porcine
      pseudorabies virus was performed.

PMID- 11450145
TI  - [Chronic fatigue and immune dysfunction syndrome].

PMID- 11450146
TI  - [Live cold-adapted reassortant influenza vaccines].
AB  - The author reviews studies of live cold-adapted reassortant influenza vaccines
      developed in Russia and USA. These vaccines are safe and weakly reactogenic for
      all age groups. The vaccines (two immunizations) are highly effective in children
      of preschool and school age and far less effective in adults. For elderly
      subjects simultaneous vaccination with live and inactivated vaccines is
      recommended. The probability of influenza prevention by a single injection of
      cold-adapted vaccines is to be further investigated. Modern data indicate that
      cold-adapted reassortant influenza vaccines can be used for influenza prevention
      only in children of preschool and school age.

PMID- 11450147
TI  - [Direct stent implantation under control of intracoronary ultrasonography.
      Immediate and late results].
AB  - Stents of a new generation have been developed, permitting immediate implantation
      without predilatation of the lesion site. Intracoronary ultrasound (ICUS) has
      been found useful in precise evaluation of stent expansion and in improvement of
      long-term therapeutic outcomes. The purpose of the study was to evaluate the
      safety and efficacy of direct stent implantation using intracoronary ultrasound.
      The study comprised 30 patients (8 women and 22 men) aged below 70 years with
      stable and unstable angina pectoris. ICUS was performed at baseline before making
      a decision about direct stent implantation and during the procedure to evaluate
      stent expansion. Direct stenting was performed in 26 patients achieving an
      angiographically and clinically optimal result (100% efficacy). In four patients
      direct stenting was abandoned because of massive calcifications in the affected
      artery detected by ICUS at baseline. During the 9-month follow-up recurrence of
      anginal pain requiring repeated intervention was observed in 3 patients (11.5%).
      CONCLUSIONS: The use of ICUS prior to direct stenting considerably improves the
      efficacy of the procedure and long-term therapeutic outcomes. Before wide
      popularisation of direct stenting under ICUS guidance it is necessary to carry
      out multicentre randomised clinical studies to verify the expected improvement of
      long-term results as compared with conventional stent implantation with pre
      dilatation.

PMID- 11450148
TI  - [Function of the left atrial appendage after electrical cardioversion of atrial
      fibrillation to sinus rhythm].
AB  - INTRODUCTION: It is widely believed that atrial fibrillation appears in a
      secondly manner to atrial enlargement. Morfological alteration might be the
      source of disturbance of electrical activation and mechanical function to fibres
      that facilitate arrhythmia preservation as well as life threatening
      complications. THE OBJECTIVE: It is crucial to establish whether reversion of
      atrial fibrillation to sinus rhythm causes size diminishment and function
      improvement of the left atrial appendage, which creates hope to avoid dangerous
      complications, particularly systemic embolisation. DATA AND METHODOLOGY: 30
      patients were qualified including 18 males and 12 females aged between 52 and 86
      (average age was 63.81 +/- 9.22). All the patients suffered from nonrheumatic
      atrial fibrillation. The echocardiographic examination was conducted before
      reversion of atrial fibrillation, right after reaching sinus rhythm and after 6
      months observation at sustained sinus rhythm. During the transesophageal
      echocardiographic examination the following parameters were investigated:
      LAApodl, LAApoprz, LAAobw, LAApole, LAAF, LAAB, LAAF intg, LAAB intg, spontaneous
      echocardiographic contrast, thrombus. RESULTS: Left atrial appendage size right
      after reversion of atrial fibrillation did not considerably differ from the
      values registered at the time of arrhythmia. It significantly diminished in the
      case of sustained stabilisation of sinus rhythm. The diminishment of the left
      atrial appendage size was connected with its function improvement expressed by
      increased maximum filling and emptying velocities as well as their integrals. SEC
      appearance frequency considerably increased right after reaching sinus rhythm.
      SEC appeared very rarely in the examination after 6 months. No single case of THR
      in LAA was noted. At the same time several cases of THR were disclosed both
      before and directly after restoration of sinus rhythm. CONCLUSIONS: Sinus rhythm
      restoration and its sustaining for a longer period of time results in size
      diminishing and function improvement of left atrial appendage. The stability of
      sinus rhythm is closely tied with thromboembolism risk factors.

PMID- 11450149
TI  - [Evaluation of helper T lymphocyte subpopulations: naive (CD4+CD45RA+), memory
      (CD4+CD45RO+) and co-expression of phenotypes CD45RA+ and CD45RO+ in preclinical
      phases of diabetes type 1 (prediabetes)].
AB  - There is an increasing evidence that T helper lymphocytes (CD4+) play a key role
      in the etiopathogenesis of type 1 diabetes. The aim of the present study was to
      evaluate the presence of T helper lymphocyte subpopulations: naive (CD4+CD45RA+),
      memory cells (CD4+CDRO+) and lymphocytes coexpressing both studied phenotypes
      (CD4+CD45RA+CD45RO+) in subjects at risk of type 1 diabetes (first degree
      relatives of IDDM patients with autoantibodies) in comparison to age and sex
      matched controls. We observed higher percentages of lymphocytes coexpressing
      CD45RA and CD45RO antigens in peripheral blood of first degree relatives with
      "pro-diabetogenic" DRB1*0401 allele and/or with impairment of first phase of
      insulin release (FPIR) in IVGTT. The CD4+CD45RA+/CD4+CD45RO+ cells ratio was
      significantly lower in subjects with protective DQB1*0602 alelle and/or higher
      FPIR levels. The alterations of CD45RA and CD45RO antigens expression on T helper
      cells in prediabetics suggest the significant role of naive or/and memory CD4+ T
      cell subsets in the pathogenesis of diabetes type 1. It could be suggested that
      CD4+CD45RA+/CD4+CD45RO+ ratio could serve as surrogate marker of diabetes type 1
      risk development and presumably for estimation of the efficacy of the preventive
      procedures in subjects at high risk of IDDM, but further prospective studies are
      needed.

PMID- 11450150
TI  - [Glucose homeostasis in children. I. Regulation of blood glucose].
AB  - The amount of glucose in the circulation depends on its absorption from the
      intestine, uptake by and release from the liver and uptake by peripheral tissues.
      Insulin and glucagon together control the metabolities required by peripheral
      tissues and both are involved in maintaining glucose homeostasis. Insulin is
      considered to be an anabolic hormone in that it promotes the synthesis of
      protein, lipid and glycogen. The key target tissues for insulin are liver,
      muscles and adipose tissue. Glucagon acts largely to increase catabolic
      processes. Between meals or during fast, the most tightly regulated process is
      the release of glucose from the liver. During fasting glucose is produced from
      glycogen and is formed by enzymes on the gluconeogenic pathway. Fetal metabolism
      is directed to ensure anabolism with formation of glycogen, fat and protein.
      Glucogen is stored in the liver and serves as the immediate source of new glucose
      during first few hours after birth. Glucose is the most important substrate for
      brain metabolism. Due to the large size of neonatal brain in relation to body
      weight cerebral glucose consumption is particularly high. Postnatal hormonal
      changes have a central role in regulating glucose mobilization through
      glycogenolysis and gluconeogenesis. The initial glucagon surge is the key
      adaptive change which triggers the switch to glucose production. The control of
      insulin and glucagon secretion is of fundamental importance during first hours
      after birth. Children have a decreased tolerance to starvation when compared with
      adults, they are more prone to develop hypoglycaemia after short fasting. The
      faster rate in the fall of blood glucose and gluconeogenic substrates and rapid
      rate of ketogenesis are characteristic features of fasting adaptation in
      children.

PMID- 11450151
TI  - [Aging and so called "youth hormones". Potential influence of exercise training].
AB  - Plasma levels of dehydroepiandrosterone sulphate (DHEAS), insulin-like growth
      factor-I (IGF-I), and testosterone decline with ageing. These hormones share some
      biological activities which counteract the aging processes: increase in fat-free
      mass, decrease of adipose tissue and globally increased fitness and well being.
      It seems that lower levels of these hormones may reflect partially lower physical
      activity and fitness of older subjects. If further longitudinal studies confirm
      this, regular participation in exercise training would become a useful
      alternative to hormone replacement therapy.

PMID- 11450152
TI  - [Lupus erythematosus in newborns].
AB  - Neonatal lupus erythematosus is an uncommon disease described mainly through case
      reports. In this paper the pathogenesis, epidemiology, skin and organ
      manifestations of the disease were presented. The necessity of co-operation
      between physicians of different specialisations in the prevention and treatment
      was underlined.

PMID- 11450153
TI  - [Is Helicobacter pylori infection a zoonosis?].
AB  - On the basis of papers review there are presented the possibilities of
      Helicobacter pylori (H. pylori) infection in animals and the route of
      transmission. The discovery of bacteria has changed our approach to the
      etiopathogenesis and treatment of some digestive tract diseases. The prevalence
      of H. pylori in some populations and socioeconomic factors confirms the man-to
      man mode of transmission with a human being as a main reservoir. There was
      confirmed the correlation between the stomach colonization of H. pylori in some
      animals, particularly those living in a human environment, and the route of
      transmission. Besides many studies performed on domestic animals and primate
      monkeys it is not clear, whether H. pylori infection can be accepted as a
      zoonosis. Many investigators confirmed the presence of bacteria in the animal
      stomach. There is a lack of data, whether the bacteria coming from other sources
      than food infected by the man could colonize the stomach, and whether it can
      cause the gastric mucosa changes by the viable forms presented in feces. If
      scientists are still interested in H. pylori the mentioned problems will probably
      be elucidated.

PMID- 11450154
TI  - [Diagnosis and treatment of nonvariceal upper gastrointestinal bleeding].
AB  - This review of nonvariceal upper gastrointestinal bleeding is based on papers
      published during the last years. Endoscopy has an important role in the
      evaluation of the patient with upper GI bleeding. Endoscopic management does
      reduce rates of rebleeding, surgery, and mortality. Several endoscopic techniques
      and results have been showed in this article.

PMID- 11450155
TI  - [Pathogenesis and significance of gastroduodenal reflux].
AB  - For over a century duodenogastric reflux (DGR) has been considered the main cause
      of the primary or secondary alkaline gastritis. In the first case it occurred in
      patients who had not been operated earlier, in the latter one in those after
      surgery of stomach, duodenum, gallbladder and bile ducts. Since first time many
      reports of clinical and experimental studies have demonstrated destructive effect
      of pancreatic enzymes, bile acids and their by-products on stomach mucose
      producing in consequence non-specific histologic lesions. It has been also
      observed that duodenogastric reflux plays the basic role in the patho-genesis of
      gastritis and other GI tract diseases (gastric ulcer, reflux oesophagitis,
      progressing metaplasia or oesophageal and gastric cancer). As far as diagnosing
      of alkaline gastritis requires histologic confirmation, duodenogastric reflux
      brings many more problems. However, the progress in medicine and technology allow
      direct measurement of quality and quantity of this reflux.

PMID- 11450156
TI  - [The role of laparoscopy in treatment of inguinal hernia].
AB  - The epidemiology, symptomatology and complications of the inguinal hernia were
      presented. Indications for operative treatment were discussed according to
      contemporary approach to currently used techniques, particularly laparoscopy. The
      anatomy of the groin seen from the inside as during laparoscopy was described.
      Different techniques of laparoscopic herniorrhaphy with particular attention to
      TAPP method were discussed. Drawbacks, advantages and complications of those
      techniques were given.

PMID- 11450157
TI  - [Comparison of clinical status and long-term outcome of patients with angina
      pectoris and normal coronary vessels in coronary angiography or insignificantly
      narrowed coronary arteries].
AB  - Among patients investigated with coronary angiography because of effort chest
      pains, 8-30% are found to have insignificantly narrowed coronary arteries. In
      this group there are patients with angiographically normal coronary arteries and
      patients with hemodynamically insignificant atherosclerotic plaques. The aim of
      this study was to compare clinical status and long-term outcome of patients with
      effort angina whose epicardial coronary arteries were angiographically normal
      (Group 1) and patients with luminal diameter stenoses of maximum 30% (Group 2).
      Between III'91 and IV'97 we identified 230 patients who underwent coronary
      angiography in the Department of Coronary Artery Disease in Cracow. At the end of
      the follow-up the patients were asked to complete the self-report questionnaires
      which evaluated the course of the disease after discharge from the Department and
      present symptoms. On the basis of the medical records from the hospitalization in
      the Department and returned questionnaires data of 142 patients (Group 1: 89
      patients, 46 men and 43 women, mean age 48.10 +/- 9.2 years; Group 2: 53
      patients, 36 men and 17 women, mean age 52.51 +/- 9.6 years) were analyzed. Group
      2 patients were older (p = 0.007), with higher prevalence of men (p = 0.05). The
      mean follow-up was 3.47 +/- 1.7 years for Group 1 and 2.85 +/- 1.7 years for
      group 2 (p = NS). Left ventricle contractility was normal in both groups. The
      occurrence of atherosclerosis risk factors was more frequent in Group 2 patients
      and didn't change significantly over the observation period. There were no deaths
      or new myocardial infarctions during the observation. Unstable angina occurred in
      4 (2.8%) of patients. 33 patients (23.2%) reported hospital treatment for chest
      pain with mean frequency 0.13 +/- 0.3 hospitalizations/year in Group 1 and 0.09
      +/- 0.17 in Group 2 (p = NS). Before coronary angiography this index was
      significantly higher -0.57 +/- 0.8 hospitalizations/year in group 1 and 0.51 +/-
      0.7 in group 2 (p < 0.001 for both groups). Anginal symptoms improved
      significantly over the observation period. Before coronary angiography majority
      of patients (60.5% Group 1 patients and 58.3% of Group 2 patients) defined their
      angina as severe comparing to respectively 7.1% and 2.1% of patients at the end
      of follow-up (p < 0.05 for both groups). Only 8 (5.6%) of patients remained
      entirely asymptomatic at the end of the study. During the observation 7 (4.9%) of
      patients returned to work while 30 (21.1%) of patients retired for medical
      reasons out of which 25 (17.6%) were due to heart disease. During the follow-up
      there were no differences between the groups in the professional activity of
      patients. Group 2 patients were receiving more cardiac medications (mean 2.63 +/-
      0.8 vs 2.18 +/- 0.9 at the discharge from the Department; p. = 0.05 and mean 2.52
      +/- 0.9 vs 2.02 +/- 1.0 at the end of follow-up; p = 0.04). Group 2 patients were
      more frequently taking nitrates (86.3% vs 53.7% at the discharge from the
      Department; p < 0.001 and 77.1% vs 60.9% at the end of the study; p = 0.05) and
      diuretics. CONCLUSIONS: 1. During follow-up (mean 3.4 years) there were no
      differences between the groups in the presence of symptoms, frequency of
      hospitalizations and occurrence of acute coronary events. 2. In both groups
      severity of anginal symptoms and frequency of hospitalizations decreased
      significantly. 3. The persistence of cardiac symptoms might have been caused by
      the presence of atherosclerosis risk factors during the follow-up.

PMID- 11450158
TI  - [Hemorrhagic cystitis related to the high-dose conditioning therapy in a bone
      marrow recipient].
AB  - Hemorrhagic cystitis (HC) is the syndrome of hematuria combined with symptoms of
      lower urinary tract irritation in the absence of bacterial infection or
      generalized hemorrhagic diathesis. HC often occurs as a difficult complication
      after autologous as well as allogeneic hematopoietic cell transplantation (HCT).
      It may be secondary to pretransplant preparative regimen (chemotherapy and/or
      radiation therapy) or viral infection by adenovirus, JC and BK viruses. The most
      effective treatment for HC has not been established yet. We report a case of a 17
      year-old male with common acute lymphoblastic leukemia (cALL) in second CR, who
      was treated with high-dose chemotherapy (BuCy conditioning regimen) followed by
      autologous bone marrow transplantation (ABMT), complicated by hemorrhagic
      cystitis on day 0 (several hours after infusion of transplant material). The
      immediate use of increased dose of 2-mercaptoethane sulfonate sodium (mesna),
      bladder irrigation and intensive hydration with forced diuresis resulted in
      resolution of macroscopic hematuria on day +3 after the transplant and urinary
      tract recovery with normalization of urine analysis parameters on day +7.

PMID- 11450159
TI  - [Disturbances of rhythm and atrio-ventricular conduction in digitalis overdose.
      Case reports].
AB  - Three cases of patients with symptoms of digitalis overdosage were presented. The
      principal manifestations included complex supraventricular dysrhythmias and atrio
      ventricular conduction disturbances. In the discussion a special attention was
      paid to digitalis dosage. Multiple factors influencing plasma concentration of
      digitalis including pharmacokinetics, bioavailability and drug interactions with
      glycosides were described. Short review of toxic manifestations of digitalis was
      made and the treatment of digitalis intoxication was outlined.

PMID- 11450160
TI  - [Angiotensin-1-blocker].

PMID- 11450161
TI  - [Clinical pharmacology of angiotensin II receptor antagonists].
AB  - Angiotensin II is not only generated by the circulating ACE (Angiotensin II
      converting enzyme) but also locally in several tissues. Therefore substances were
      developed, which act directly at its receptor. This receptor contains 2 subtypes,
      which are influenced by these antagonists in a different way. The marketed drugs
      of this group have different pharmacokinetic properties.

PMID- 11450162
TI  - [Angiotensin receptor blockers--significance for the therapy of hypertension].
AB  - Angiotensin receptor antagonists (ARB) are equally effective but better tolerated
      than all the other blood pressure lowering agents. The reason, why they are not
      subscribed as first line drugs for uncomplicated hypertension, is the higher
      price for these products. What the real difference in costs is, remains unclear
      because calculations are missing to what extent lesser controls of therapy would
      shift the balance in favour of the ARBs. For other indications than hypertension,
      but often associated with that condition, be it per se or as a consequence of it,
      the effects of the ARBs are studied in large trials these days. For some of them
      the benefit, which has been proven for ACE inhibitors, is not yet established for
      the ARBs, but evidence emerges that they are also useful in the treatment of
      cardiac failure, left ventricular hypertrophy and diabetic and other kinds of
      nephropathy. A large percentage of hypertensive patients can be treated
      effectively with ARBs without considerable side effects, thus increasing
      adherence and minimizing the necessity of safety controls.

PMID- 11450163
TI  - [Angiotensin I receptor blockers for heart failure].
AB  - Angiotensin conversion enzyme inhibitors (ACE-inhibitors) have long been the only
      possibility to influence the renin angiotensin system (RAS) and its often fatal
      influences in heart failure. In the last few years specific blockers of the
      angiotensin 1 receptor (AT I blockers) offered a new possibility for this
      therapeutic target. In contrast to ACE inhibitors AT I blockers are relatively
      new and, therefore, few data on heart failure are available. The first head-to
      head studies that compared AT I blockers and ACE-inhibitors and their effect on
      mortality did not show a reduced mortality in the AT I blocker groups. Based on
      the available data AT I blockers should be used in heart failure patients who are
      intolerant of ACE-inhibitors.

PMID- 11450164
TI  - [Angiotensin II type-1-receptor antagonists from the viewpoint of nephrology].
AB  - ACE (Angiotensin Converting Enzyme) inhibitors and angiotensin II type 1 receptor
      antagonists increase the effective renal plasma flow dose dependently, whereas
      glomerular filtration rate does not change. Both substances reduce dose
      dependently arterial blood pressure, glomerular capillary pressure and
      proteinuria and are probably comparably renoprotective due to haemodynamic and
      non-haemodynamic (e.g. antiproliferative) effects. These data indicate that the
      renoprotective effects of ACE inhibitors and angiotensin II receptor antagonists
      are the results of inhibition of angiotensin II and not due to inhibition of
      bradykinin degradation. Several studies suggest an additive renoprotective effect
      of ACE inhibitors and angiotensin II receptor antagonists. However, controlled
      clinical studies are lacking. Experimental data suggest that the combination of
      AT1 and AT2 receptor blockers or treatment with ACE inhibitors reduce more
      effectively inflammatory cell infiltration into the kidney than angiotensin II
      type 1 receptor antagonists alone. Long-term clinical trials using angiotensin II
      type 1 receptor antagonists are needed before these substances can be recommended
      as comparably renoprotective as ACE inhibitors.

PMID- 11450165
TI  - [Angiotensin II type-1 receptor antagonists and diabetes mellitus].
AB  - Arterial hypertension is a major risk factor for microangiopathic diabetic
      complications and associated with an increased cardiovascular morbidity and
      mortality. An intensified antihypertensive treatment reduces microangiopathic
      complications and cardiovascular morbidity and mortality in diabetic patients.
      Even in normotensive type 1 and type 2 diabetic patients, the treatment with ACE
      inhibitors may prevent the later development of diabetic nephropathy. Treatment
      with ACE inhibitors increases the concentrations of bradykinin, which is
      responsible for the side effects such as cough and urticaria in some patients. On
      the other hand, bradykinin may have beneficial intrarenal effects decreasing the
      intraglomerular pressure. The novel angiotensin II receptor type 1 antagonists do
      not influence the bradykinin concentrations and seem to be tolerated by patients
      suffering from chronic cough with ACE inhibitor therapy. It is still unclear
      whether the different intrarenal effects are of clinical relevance in the long
      term treatment of diabetic patients. In studies with diabetic animals the
      nephroprotective effects of ACE inhibitors and angiotensin II type 1 receptor
      antagonists are comparable. It was shown that glucose and lipid metabolism is not
      influenced by treatment with angiotensin II type 1 receptor antagonists. Further
      compared to Felodipine the reduction of urinary albumin excretion rate (UAER) was
      more pronounced by Losartane in Chinese type 2 diabetic patients. Short-term
      studies directly comparing the renal effects of ACE inhibitors with AT II type 1
      receptor antagonists revealed similar reduction of blood pressure and albumin
      excretion rate in patients with diabetic nephropathy, so a combination of both
      substances might be useful. Data from ongoing long-term trials are still missing.
      Further, it is unknown whether different phenotypes of the ACE gene (DD, II
      polymorphism) require different therapeutic options. In conclusion, treatment
      with angiotensin II receptor antagonists is well-tolerated and has no adverse
      effects on metabolic control in diabetic patients. The beneficial effect on
      microangiopathic complications however has to be proven in randomized long-term
      studies in direct comparison with ACE inhibitors, which were clearly shown to
      delay the development and progression of diabetic nephropathy.

PMID- 11450166
TI  - [Research steps of applied medicine].
AB  - The history of science in medicine started 1543 with Vesal's book "De corporis
      humani fabrica". Four hundred years later, in 1955, Braun opened up the enormous
      unexplored territory of applied medicine for future scientific investigation with
      his publication "The law of regularly case distribution". As usual in such
      research work initially the most important tasks were to uncover the inherent
      laws and to create an appropriate specific terminology.

PMID- 11450167
TI  - [Management of hallucinating patients].
AB  - Hallucinations are perceptions lacking any extern or physical stimulus. They can
      affect all senses and may occur in the course of different physical or
      psychiatric diseases. Patients experiencing hallucinations may derive the
      conviction that the contents of their hallucinations and the consequent
      interpretations are real, therefore they may try to convince their relatives and
      friends. Thus it has proved helpful to follow certain rules in the treatment of
      these patients. It is important not only to diagnose the basic disorder or
      illness but also to deal with the patient's anxiety, respect his/her perceptions
      and to try to establish alternative models of explanation. Apart from therapy of
      the underlying disorder it is wise to recommend psychotherapy and the attendance
      of self-help groups.

PMID- 11450168
TI  - [Society-research-diagnosis: have classification problems in psychiatry been
      overcome at the beginning of the new millennium?].
AB  - Although diagnostics of organic psychoses already had been quite well established
      at the beginning of the last century, no satisfactory results had been achieved
      in the field of functional psychoses. This led to a return towards the concept of
      "unitarian psychoses" and thus to a revival of cross-sectional diagnoses. With
      the development of psychopharmacological compounds the need for exact demarcation
      of disease grew. Around this time syndromatological classification systems that
      were supposed to be used internationally have been developed. In the course of
      the last thirty years the argument about the meaning of psychiatric diagnoses
      rose anew; the necessity of standardized means of psychiatric diagnoses was
      contrasted by the fact that there was no way of defining disease entities for
      clinical research. A polydiagnostic approach as well as clinical diagnose of the
      illness course--using single symptoms as predictors of the disease's course-
      could point to a solution.

PMID- 11450169
TI  - The search for the wandering thymostat: a review of some developments in bipolar
      disorder research.

PMID- 11450170
TI  - Bipolar disorder: leads from the molecular and cellular mechanisms of action of
      mood stabilizers.
AB  - BACKGROUND: New research is dramatically altering our understanding of the
      molecular mechanisms underlying neuronal communication. AIM: To elucidate the
      molecular mechanisms underlying the therapeutic effects of mood stabilizers.
      METHOD: Results from integrated clinical and laboratory studies are reviewed.
      RESULTS: Chronic administration of lithium and valproate produced a striking
      reduction in protein kinase C (PKC) isozymes in rat frontal cortex and
      hippocampus. In a small study, tamoxifen (also a PKC inhibitor) had marked
      antimanic efficacy. Both lithium and valproate regulate the DNA binding activity
      of the activator protein I family of transcription factors. Using mRNA
      differential display, it was also shown that chronic administration of lithium
      and valproate modulates expression of several genes. An exciting finding is that
      of a robust elevation in the levels of the cytoprotective protein, bcl-2.
      CONCLUSIONS: The results suggest that regulation of signalling pathways may play
      a major part in the long-term actions of mood stabilizers. Additionally, mood
      stabilizers may exert underappreciated neuroprotective effects.

PMID- 11450171
TI  - Neuropsychology of bipolar disorder.
AB  - BACKGROUND: Although the presence of wide-ranging neuropsychological deficits in
      individuals with major depression is well established, few studies have
      investigated the nature of cognitive impairment in patients with bipolar
      disorder. AIMS: To review research of the neuropsychology of bipolar disorder,
      with special attention to the relationship between mood and cognitive
      functioning. METHOD: Literature review. RESULTS: Findings generally demonstrate
      mania-related impairments on conventional neuropsychological tests, with direct
      comparisons of patients with mania and patients with depression failing to find
      group differences. More recent work has sought to differentiate these disorders
      by employing tasks with affective components. This research has demonstrated
      biases for processing positive and negative stimuli in patients with mania and
      depression, respectively. CONCLUSIONS: Future studies, employing tasks that
      require cognitive and emotional processing, should improve our understanding of
      the deficits observed in depression and mania. Neuroimaging studies of the neural
      regions that underlie cognitive processing of affective meaning suggest that the
      medial and orbitofrontal prefrontal cortex may be particularly involved.

PMID- 11450172
TI  - Molecular genetics of bipolar disorder.
AB  - BACKGROUND: A robust body of evidence from family, twin and adoption studies
      demonstrates the importance of genes in the pathogenesis of bipolar disorder.
      Recent advances in molecular genetics have made it possible to identify these
      susceptibility genes. AIMS: To present an overview for clinical psychiatrists.
      METHOD: Review of current molecular genetics approaches and emerging findings.
      RESULTS: Occasional families may exist in which a single gene plays a major role
      in determining susceptibility, but the majority of bipolar disorder involves more
      complex genetic mechanisms such as the interaction of multiple genes and
      environmental factors. Molecular genetic positional and candidate gene approaches
      are being used for the genetic dissection of bipolar disorder. No gene has yet
      been identified but promising findings are emerging. Regions of interest include
      chromosomes 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Candidate gene
      association studies are in progress but no robust positive findings have yet
      emerged. CONCLUSION: It is almost certain that over the next few years the
      identification of bipolar susceptibility genes will have a major impact on our
      understanding of disease pathophysiology. This is likely to lead to major
      improvements and treatment in patient care, but will also raise important ethical
      issues.

PMID- 11450173
TI  - Genetic studies of bipolar affective disorder in large families.
AB  - BACKGROUND: Genetic factors are known to be important in the aetiology of bipolar
      disorder. AIMS: To review linkage studies in extended families multiply affected
      with bipolar disorder. METHOD: Selective review of linkage studies of bipolar
      disorder emphasising the gains and drawbacks of studying large multiply-affected
      families and comparing the statistical methods used for data analysis. RESULTS:
      Linkage of bipolar disorder to several chromosome regions including 4p, 4q, 10p,
      12q, 16p, 18q, 21q and Xq has first been reported in extended families. In other
      families chromosomal rearrangements associated with affective illnesses provide
      signposts to the location of disease-related genes. Statistical analyses using
      variance component methods can be applied to extended families, require no prior
      knowledge of the disease inheritance, and can test multilocus models. CONCLUSION:
      Studying single large pedigrees combined with variance component analysis is an
      efficient and effective strategy likely to lead to further insights into the
      genetic basis of bipolar disorders.

PMID- 11450174
TI  - Serial analysis of gene expression in the frontal cortex of patients with bipolar
      disorder.
AB  - BACKGROUND: Bipolar disorder is a serious brain disease affecting more than a
      million individuals living in the USA. Epidemiological studies indicate a role
      for both genetic and environmental factors in the pathogenesis of this disorder.
      AIM: To identify RNA transcripts that are up- or down-regulated in the frontal
      cortex regions of individuals with bipolar disorder. METHOD: Serial analysis of
      gene expression (SAGE) and reverse transcriptase-polymerase chain reaction were
      used to identify RNA transcripts which are differentially expressed in the
      frontal cortex of brains obtained postmortem from individuals with bipolar
      disorder compared with other psychiatric and control conditions. RESULTS: Levels
      of RNA transcripts encoding the serotonin transporter protein and components of
      the NF-kappa B transcription factor complex are significantly increased in
      individuals with bipolar disorder compared with unaffected controls. Increased
      levels of expression of these RNA transcripts were also detected in the brains of
      some individuals with schizophrenia and unipolar depression. CONCLUSION: The SAGE
      technique offers promise for the characterisation of complex human brain
      diseases.

PMID- 11450175
TI  - Neuroanatomical studies on bipolar disorder.
AB  - BACKGROUND: Neuroimaging data showing structural and functional brain
      abnormalities in mood disorders suggest that brain alterations at the
      neurohistological level may underlie the macropathology seen by imaging in vivo.
      AIMS: To summarise recent postmortem studies on affective disorders, with a focus
      on bipolar disorder. METHOD: Literature review and discussion of results from
      volumetric, cyto-architectural and immunohistochemical analyses. RESULTS: Basal
      ganglia are smaller in patients with depression irrespective of diagnostic
      polarity. In addition, higher neuron numbers have been reported in the locus
      caeruleus of patients with bipolar disorder compared with those with unipolar
      depression. Patients with bipolar as well as unipolar illness show subtle
      structural deficits in the dorsal raphe. Histological data are consistent with a
      regional reduction in the synthesis of noradrenalin and serotonin, which appears
      to be compensated by antidepressants. CONCLUSION: Preliminary results suggest
      that, aside from functional dysregulation, subtle structural abnormalities in the
      brain may contribute to the pathogenesis of mood disorders.

PMID- 11450176
TI  - Use of antipsychotic drugs and lithium in mania.
AB  - BACKGROUND: Studies highlighting the difficulties associated with lithium suggest
      that the role of antipsychotic drugs and mood stabilizers in bipolar disorder
      should be reconsidered. AIMS: To review the efficacy and mode of action of
      antipsychotic drugs in mania, and to consider the differences between official
      guidelines and routine clinical practice in the use of these agents for mania.
      METHOD: Review of research, guideline- and practice-based literature. RESULTS:
      Guidelines recommend lithium or valproate as first-line treatments for mania, and
      antipsychotic agents only as 'adjuncts' for agitation, dangerous behaviour or
      psychosis. However, in routine practice, antipsychotic drugs are often
      prescribed. The effectiveness of these agents in mania has been established by
      several studies; newer atypical compounds demonstrate antimanic efficacy with a
      reduced incidence of neurological side-effects. CONCLUSION: Antipsychotic drugs
      are important in the treatment of bipolar disorder and mania. Future studies
      should evaluate the long-term efficacy and safety of newer atypical antipsychotic
      agents, and the place of anticonvulsants in combination with antipsychotics in
      bipolar disorder.

PMID- 11450177
TI  - Evolving methodologies in bipolar disorder maintenance research.
AB  - BACKGROUND: During the development of a new treatment for bipolar disorder,
      maintenance studies are used to evaluate the ability of the putative mood
      stabilizer to prevent relapse and recurrence of further episodes. Comparisons
      with the early bipolar disorder maintenance studies indicate that the
      methodologies of recent trials have evolved substantially. AIMS: To review the
      methods used in the first- and second-generation maintenance studies,
      highlighting the differences of the various designs. METHOD: Literature review.
      RESULTS: Methods that have evolved the most include patient enrollment,
      randomisation schemes and the use of outcome measures and statistical analyses.
      In addition, regulatory and commercial issues have also influenced study design.
      CONCLUSION: There is little consensus on the methodology of bipolar disorder
      maintenance studies. As the integration of newer therapies into routine clinical
      practice is dependent on the evidence from controlled studies, it is essential
      that future maintenance trials in bipolar disorder achieve adequate
      methodological rigour without sacrificing overall feasibility.

PMID- 11450178
TI  - Cognitive therapy as an adjunct to medication in bipolar disorder.
AB  - BACKGROUND: There is increasing support for the use of cognitive behaviour
      therapy as an adjunct to medication for patients with bipolar disorder. AIMS: To
      explore current psychological models of bipolar disorder, describing the clinical
      rationale for using cognitive therapy and providing a brief overview of the
      approach. METHOD: Results from outcome studies are discussed. RESULTS:
      Preliminary findings indicate that cognitive therapy may be beneficial for
      patients with bipolar disorder. The collaborative, educational style of cognitive
      therapy, the use of a stepwise approach and of guided discovery is particularly
      suitable for patients who wish to take an equal and active role in their therapy.
      CONCLUSIONS: Randomised, controlled trials of cognitive therapy in bipolar
      disorder are required to establish the short-term and long-term benefits of
      therapy, and whether any reported health gain exceeds that of treatment as usual.

PMID- 11450179
TI  - The Stanley Foundation Bipolar Network. I. Rationale and methods.
AB  - BACKGROUND: The Stanley Foundation Bipolar Network (SFBN) was created to address
      the paucity of help studies in bipolar illness. AIMS: To describe the rationale
      and methods of the SFBN. METHOD: The SFBN includes five core sites and a number
      of affiliated sites that have adopted consistent methodology for continuous
      longitudinal monitoring of patients. Open and controlled studies are performed as
      patients' symptomatology dictates. RESULTS: The reliability of SFBN raters and
      the validity of the rating instruments have been established. More than 500
      patients are in continuous daily longitudinal follow-up. More than 125 have been
      randomised to one of three of the newer antidepressants (bupropion, sertraline
      and venlafaxine) as adjuncts in a study of mood stabilizers and 93 to omega-3
      fatty acids. A number of open clinical case series have been published.
      CONCLUSIONS: Well-characterised patients are followed in a detailed continuous
      longitudinal fashion in both opportunistic case series and double-blind,
      randomised controlled trials with reliable and validated measures.

PMID- 11450180
TI  - The Stanley Foundation Bipolar Network. 2. Preliminary summary of demographics,
      course of illness and response to novel treatments.
AB  - BACKGROUND: The Stanley Foundation Bipolar Network (SFBN) evaluates treatments,
      course and clinical and neurobiological markers of response in bipolar illness.
      AIMS: To give a preliminary summary of emerging findings in these areas. METHOD:
      Studies with established and potentially antimanic, antidepressant and mood
      stabilising agents range from open case series to double-blind randomised
      clinical trials, and use the same core assessment methodology, thereby optimising
      the comparability of the outcomes. The National Institute of Mental Health Life
      Chart Method is the core instrument for retrospective and prospective
      longitudinal illness description. RESULTS: The first groups of patients enrolled
      show a considerable degree of past and present symptomatology, psychiatric
      comorbidity and functional impairment. There are associations of both genetic and
      early environmental factors with more severe courses of illness. Open case series
      with add-on olanzapine, lamotrigine, gabapentin or topiramate show a differential
      spectrum of effectiveness in refractory patients. CONCLUSIONS: The SFBN provides
      important new data for the understanding and treatment of bipolar disorder.

PMID- 11450181
TI  - Long-term clinical effectiveness of lithium maintenance treatment in types I and
      II bipolar disorders.
AB  - BACKGROUND: The effectiveness of lithium is being questioned increasingly and
      requires clarification. AIMS: To assess the effectiveness of lithium treatment in
      depression and mania, syndromal types I and II, with predominantly mixed or
      psychotic episodes or rapid cycling, during treatment resumed following
      discontinuation, and across three decades. METHOD: The longitudinal course of 360
      patients with bipolar disorder compliant with lithium treatment for at least 1
      year and without comorbidity for substance use disorder was reviewed. RESULTS:
      Risk of single-episode recurrences, a common index of treatment failure, was
      similar to that in other reports. Both episode frequency and 'time ill' improved
      more in type II than type I cases. Reduced morbidity during treatment was similar
      in patients with mixed or psychotic episodes, or rapid cycling, and in less
      complex cases. Retreatment yielded minor decrements in response, and there was no
      tendency for lesser responses in more recent years. CONCLUSIONS: Based on overall
      affective morbidity, long-term lithium treatment in compliant patients without
      comorbid substance use disorder, though imperfect, remains effective, even in
      subgroups of supposedly poor prognosis.

PMID- 11450182
TI  - Bipolar disorder: clinical uncertainty, evidence-based medicine and large-scale
      randomised trials.
AB  - BACKGROUND: The increasing use of the methods of evidence-based medicine to keep
      up-to-date with the research literature highlights the absence of high-quality
      evidence in many areas in psychiatry. AIMS: To outline current uncertainties in
      the maintenance treatment of bipolar disorder and to describe some of the
      decisions involved in designing a large simple trial. METHOD: We describe some of
      the strategies of evidence-based medicine, and how they can be applied in
      practice, focusing specifically on the area of bipolar disorder. RESULTS: One of
      the key clinical uncertainties in the treatment of bipolar disorder is the place
      of maintenance drug treatments and their relative efficacy. A large-scale study,
      the Bipolar Affective Disorder: Lithium Anticonvulsant Evaluation (BALANCE)
      trial, is proposed to compare the effectiveness of lithium, valproate and the
      combination of lithium and valproate. CONCLUSIONS: Providing reliable answers to
      key clinical questions in psychiatry will require new approaches to clinical
      trials. These will need to be far larger than previously appreciated and will
      therefore need to be collaborative ventures involving front-line clinicians.

PMID- 11450183
TI  - [What is your diagnosis? Keratoma sulcatum (pitted keratolysis)].

PMID- 11450184
TI  - [The hyperactive child: diagnosis and therapy].
AB  - After briefly defining the hyperkinetic disorder of childhood the typical process
      of clinical assessment is described. The latter includes the psychiatric
      interview with parents, child and teachers, the history of the child, the use of
      questionnaires and rating scales, neuropsychological testing and the physical
      examination of the child. Careful consideration of differential diagnoses is
      mandatory in order to avoid false negative and false positive diagnoses. The
      etiology is dominated by neurobiological concepts with a special emphasis on
      genetic causes. Treatment is multimodal giving special weight to pharmacotherapy
      with stimulants.

PMID- 11450185
TI  - [Diagnostic principles for differential therapy of psychoses].
AB  - The pharmacotherapy of psychotic disturbances is not limited on neuroleptics, but
      includes Clomethiazol and Benzodiazepines (e.g. to treat delirium) or
      antidepressants (e.g. to treat psychotic depression) too. Even more divergent is
      the psychosocial treatment of different psychotic states. In this overview the
      diagnostic principles, needed for a differential therapy of psychotic disorders,
      are described.

PMID- 11450186
TI  - [Drug treatment of functional psychotic disorders].
AB  - Psychotic symptoms occur in different psychiatric disorders. The principles of
      antipsychotic drug treatment of various non-organic psychotic disorders are
      discussed. In particular, the role of the so-called atypical antipsychotics is
      highlighted.

PMID- 11450187
TI  - [Early detection of schizophrenic psychoses].
AB  - Difficulties in early detection of schizophrenic psychosis are two-fold: the non
      specificity of the prodromal symptoms and the skepticism to or the rejection of
      the medical treatment by the patient. In this paper we focus on the central role
      of the GP. Due to the long-lasting trustful relationship with the patient's
      family he is able to establish a contact to the patient. Questions for the
      assessment of the most mentioned prodromal symptoms (behaviour, affectivity,
      cognition) are indicated. Further steps in the evaluation as well as differential
      diagnoses are pointed out. Finally, the importance of early detection of
      psychosis and the GP's role herein is shown.

PMID- 11450188
TI  - [Surgical indications and techniques in Basedow's disease, multinodular goiter
      and thyroid cancers].
AB  - This is a retrospective study of 47 near total and 30 total thyroidectomies for
      multinodular goiter, Graves' disease and thyroid cancer. Complications are rare:
      one permanent recurrent nerve palsy out of 154 nerves at risk, one definitive
      hypoparathyroidism. For a benign pathology, the former bilateral sub-total
      thyroidectomy should be replaced by a near-total thyroidectomy which leaves one
      unilateral thyroid remnant the size of a cherry. Using this technique, we did not
      observe any recurrence. Among 42 patients controlled after more than one year 1/3
      have a normal thyroid function. Systematic substitution is not indicated.
      Thyroxine should be used only if hypothyroidism develops after the operation or
      if an increase of the thyroid remnant is demonstrated. Thyroid cancer should be
      treated by total thyroidectomy, except for noninvasive papillary cancer without
      node metastasis for which a total lobectomy is sufficient.

PMID- 11450189
TI  - [Thyroid nodules. Surgical aspects].
AB  - This is a restrospective study of 176 thyroid nodules operated between 1977 and
      1990, excluding bilateral goiters. 145 were benign with 111 cold and 34 hot
      nodules; 31 were cancers. Fine needle biopsy (FNB) is useless in hot nodules. For
      the cold ones, even in recent series, FNB can give false positive or negative
      results. This means that the answer of FNB should be closely related to the
      clinical and US findings. The surgical treatment of thyroid nodules must be a
      total lobectomy including the isthmus. The recurrent laryngeal nerve must be
      followed entirely. There was no permanent nerve palsy among the 122 total
      lobectomies. The risk of developing another controlateral nodule later is low
      (2/110 cases). It is very difficult to distinguish a follicular cancer from an
      adenoma on frozen section. For this reason, the patient should be warned that a
      second operation might be necessary some days later if the definitive diagnosis
      is a follicular cancer. For a non-invasive and non-metastatic papillary cancer,
      total lobectomy is sufficient. More advanced papillary and all other thyroid
      cancers should be treated by a total thyroidectomy.

PMID- 11450190
TI  - [What should you tell your patient who has an inguinal hernia?].
AB  - Surgery of the inguinal hernia has undergone rapid progress in a decade.
      Evaluation of new techniques, prothetic and laparoscopic, are often confusing.
      Comparison with classical surgery may seem difficult to the non surgeon. Though,
      the general practitioner keeps an important place in caring for patients with
      this particular pathology. The importance of economical repercussion involved by
      hernia pathology and knowledge of the different techniques at disposition and
      their outcome should allow him to objectively guide his patient who is more and
      more informed through the media and the web.

PMID- 11450191
TI  - [Pelvic and acetabular fractures, long term results, retrospective study from
      Cadolles from 1977 to 1997].
AB  - From 1977 to 1997, 51 unstable pelvic and/or acetabular fractures were operated
      in our institution. We could control 35 after a mean postoperative period of
      nearly six years. The outcome was analysed considering several factors: pain,
      neurological and genito-urinary problems, gait, social life, Xrays and clinical
      findings. Our results match well with those of other series. Different evaluation
      scores used in the literature are compared and discussed.

PMID- 11450192
TI  - [When and how to investigate a mutation predisposing to the Lynch syndrome].
AB  - Lynch Syndrom (or Hereditary Non-polyposic Colorectal Cancer (HNPCC)) can be
      described as the presence of an autosomic dominant mutation predisposing to early
      colorectal cancer. Suggestive familial history and young patient with colorectal
      cancer should undergo thorough investigation. In Switzerland, investigation will
      first attempt to show microsatellites instability in fumoral cells, then mutation
      in blood. If positive, direct progeny and family should be tested. Those who are
      mutation free may be followed as normal population. The others should have more
      frequent colorectal and gynecologic follow-up. Surgical treatment will attempt to
      prevent synchrone or metachrone colorectal cancer by total colectomy. Preventive
      colectomy is attractive but controversial.

PMID- 11450193
TI  - [Chronic testicular pain].

PMID- 11450194
TI  - [Pancreatic injuries: diagnosis and management].
AB  - Traumatic lesions of the pancreas are rare (3-12% of abdominal trauma). In
      Central Europe most of them are due to blunt trauma. We reviewed the series from
      four university and one central hospitals in Switzerland over a period of ten to
      twenty years. Among these 75 cases, 84% were consecutive to blunt trauma. All the
      cases with an open injury were operated on rapidly. 15 patients with blunt trauma
      were treated conservatively. Out of the 58 operated patients, 20 had a caudal
      resection, 3 a pancreatico-jejunal anastomosis and 1 a duodeno-pancreatectomy.
      The others were drained. Nine patients died, 5 of them as a direct consequence of
      the pancreatic lesions. The morbidity was high (48%). After an open abdominal
      trauma, or when the patient remains unstable after blunt trauma an emergency
      laparotomy should be undertaken. It can lead to damage control surgery as a first
      step when the general and local conditions are bad. When the patient is
      hemodynamicaly stable, a conservative approach should be considered. The best
      diagnostic tools are repeated CT-scan and amylasemia. A differed operation is
      indicated only if the general and local condition deteriorate.

PMID- 11450195
TI  - [Compression of the median and radial nerves of the proximal forearm].

PMID- 11450196
TI  - [Intractable wounds, chronic wounds].

PMID- 11450197
TI  - [Current management of sigmoid diverticulosis].

PMID- 11450198
TI  - [Swiss Surgical Team. Instruction in surgery and anesthesia in Mongolia].

PMID- 11450199
TI  - [Drug therapy in sleep disorders].

PMID- 11450200
TI  - [Crisis intervention and chinese psychology. Clinical status of Confucian values
      in crisis work with three Vietnamese patients].

PMID- 11450201
TI  - [History of a surgeon: Edmond Lardy (1859-1935)].

PMID- 11450202
TI  - [Demand for medically assisted suicide or euthanasia: what does this mean? View
      of a physician working in palliative care].

PMID- 11450203
TI  - Another kick at the Kyoto can.

PMID- 11450204
TI  - Diagnosis of fibromyalgia.

PMID- 11450205
TI  - The community's voice in research.

PMID- 11450206
TI  - Inoculation blastomycosis.

PMID- 11450207
TI  - The Hajj in modern times.

PMID- 11450208
TI  - The Hajj in modern times.

PMID- 11450209
TI  - Preventive health care, 2001 update: screening and management of developmental
      dysplasia of the hip in newborns.
AB  - OBJECTIVE: To review the effectiveness of, and make practice recommendations for,
      serial clinical examination and ultrasound screening for developmental dysplasia
      of the hip (DDH) in newborns. The effectiveness of selective screening of high
      risk infants with hip and pelvic radiographs and treatment with abduction therapy
      are also examined. OPTIONS: Screening: serial clinical examination, ultrasound
      screening, radiographic evaluation. TREATMENT: abduction therapy. OUTCOMES: Rates
      of operative intervention, abduction splinting, delayed diagnosis of DDH (beyond
      3-6 months), treatment complications and false diagnostic labelling. Long-term
      functional outcomes were considered important. EVIDENCE: MEDLINE was searched for
      relevant English-language articles published from 1966 to November 2000 using the
      key words "screening," "hip," "dislocation," "dysplasia," "congenital" and
      "ultrasound." Comparative and descriptive studies and key reviews were retrieved,
      and their bibliographies were manually searched for further studies. BENEFITS,
      HARMS AND COSTS: Because most infants will have spontaneous resolution of
      nonteratologic DDH, early identification and intervention results in unnecessary
      labelling of newborns as having the problem and unnecessary treatment. Ultrasound
      screening is a highly sensitive but poorly specific measure of clinically
      relevant DDH. Abduction splinting is associated with a variety of problems, and
      its effectiveness in treating DDH is not clearly known. At least 20% of infants
      requiring operative intervention have had splint therapy. The harms of labelling,
      repetitive investigations, unnecessary splinting and resource consumption
      associated with screening are substantial. VALUES: The strength of evidence was
      evaluated using the evidence-based methods of the Canadian Task Force on
      Preventive Health Care. RECOMMENDATIONS: There is fair evidence to include serial
      clinical examination of the hips by a trained clinician in the periodic health
      examination of all infants until they are walking independently (level II-1 and
      III evidence; grade B recommendation). There is fair evidence to exclude general
      ultrasound screening for DDH from the periodic health examination of infants
      (level II-1 and III evidence; grade D recommendation). There is fair evidence to
      exclude selective screening for DDH from the periodic health examination of high
      risk infants (level II-1 and III evidence; grade D recommendation). There is fair
      evidence to exclude routine radiographic screening for DDH from the periodic
      health examination of high-risk infants (level III evidence; grade D
      recommendation). There is insufficient evidence to evaluate the effectiveness of
      abduction therapy (level III evidence; grade C recommendation), but good evidence
      to support a period of close observation for newborns with clinically detected
      DDH (level I evidence; grade A recommendation). However, there is insufficient
      evidence to determine the optimal duration of observation (level III evidence;
      grade C recommendation). VALIDATION: The members of the Canadian Task Force on
      Preventive Health Care reviewed the findings of this analysis through an
      iterative process. The task force sent the final review and recommendations to
      selected external expert reviewers, and their feedback was incorporated in the
      final draft of the manuscript. SPONSORS: The Canadian Task Force on Preventive
      Health Care is funded through a partnership between the Provincial and
      Territorial Ministries of Health and Health Canada.

PMID- 11450210
TI  - Chemoprevention of breast cancer. A joint guideline from the Canadian Task Force
      on Preventive Health Care and the Canadian Breast Cancer Initiative's Steering
      Committee on Clinical Practice Guidelines for the Care and Treatment of Breast
      Cancer.
AB  - OBJECTIVE: To assist women and their physicians in making decisions regarding the
      prevention of breast cancer with tamoxifen and raloxifene. EVIDENCE: Systematic
      review of English-language literature published from 1966 to August 2000
      retrieved from MEDLINE, HealthSTAR, Current Contents and Cochrane Library.
      VALUES: The strength of evidence was evaluated using the methods of the Canadian
      Task Force on Preventive Health Care and the Steering Committee on Clinical
      Practice Guidelines for the Care and Treatment of Breast Cancer. RECOMMENDATIONS:
      Women at low or normal risk of breast cancer (Gail risk assessment index < 1.66%
      at 5 years): There is fair evidence to recommend against the use of tamoxifen to
      reduce the risk of breast cancer in women at low or normal risk of the disease
      (grade D recommendation). Women at higher risk of breast cancer (Gail index > or
      = 1.66% at 5 years): Evidence supports counselling women at high risk on the
      potential benefits and harms of breast cancer prevention with tamoxifen (grade B
      recommendation). The cutoff for defining high risk is arbitrary, but the National
      Surgical Adjuvant Breast and Bowel Project P-1 Study included women with a 5-year
      projected risk of at least 1.66% according to the Gail index, and the average
      risk of patients entered in the trial was 3.2%. Examples of high-risk clinical
      situations are 2 first-degree relatives with breast cancer, a history of lobular
      carcinoma in situ or a history of atypical hyperplasia. As the risk of breast
      cancer increases above 5% and the benefits outweigh the harms, a woman may choose
      to take tamoxifen. The duration of tamoxifen use in such situations is 5 years
      based on the results from trials of tamoxifen involving women with early breast
      cancer. If a woman raises concerns or has already been evaluated and is
      calculated to be at high risk, then individuals experienced and skilled in
      counselling may discuss the potential benefits and harms of tamoxifen use.
      Important additional issues: Prevention of breast cancer with raloxifene: Current
      evidence does not support recommending chemoprevention of breast cancer with
      raloxifene outside of a clinical trial setting. Screening using the Gail risk
      assessment index: This index was the main eligibility criterion for enrolling
      women in the one study that showed potential benefit from chemoprevention.
      However, it has not been evaluated for use as a routine screening or case-finding
      instrument; validation of the index is required. Overall, current evidence does
      not support a shift to its routine use in physicians' offices for screening or
      case finding. However, when a woman or her physician is concerned about the
      woman's increased risk of breast cancer, the index can be a useful tool in
      deciding whether to pursue an in-depth discussion of the potential benefits and
      harms of chemoprevention. Hence, the approach to identifying women at higher risk
      who warrant counselling and shared decision-making will vary across practices.
      (The risk assessment index is available online at http://bcra.nci.nih.gov/brc/).
      [A patient version of these guidelines appears in Appendix 2.] VALIDATION: The
      authors' original text was revised by both the Canadian Task Force on Preventive
      Health Care and the Steering Committee on Clinical Practice Guidelines for the
      Care and Treatment of Breast Cancer. The final document reflects a consensus of
      these contributors. SPONSOR: Health Canada. COMPLETION DATE: February 2001.

PMID- 11450211
TI  - Did the major clinical trials of statins affect prescribing behaviour?

PMID- 11450212
TI  - Racial stereotyping and medicine: the need for cultural competence.

PMID- 11450213
TI  - Societal hierarchy and the health Olympics.

PMID- 11450214
TI  - New provincial initiatives for childhood disabilities: the imperative for
      research.

PMID- 11450215
TI  - Problems for clinical judgement: 4. Surviving in the report card era.
AB  - Health care report cards involve comparisons of health care systems, hospitals or
      clinicians on performance measures. They are going to be an important feature of
      medical care in Canada in the new millennium as patients demand more information
      about their medical care. Although many clinicians are aware of this growing
      trend, they may not be prepared for all of its implications. In this article, we
      provide some historical background on health care report cards and describe a
      number of strategies to help clinicians survive and thrive in the report card
      era. We offer a number of tips ranging from knowing your outcomes first to
      proactively getting involved in developing report cards.

PMID- 11450216
TI  - The HIV-positive dentist: balancing the rights of the health care worker and the
      patient.
AB  - We describe a hypothetical case of an HIV-positive dentist without cognitive
      impairment who uses proper infection control procedures. The dentist's physician
      notifies the medical officer of health without the dentist's consent. Although
      HIV-positive health care workers, including dentists, have been identified in the
      past, proven HIV transmission to patients is very rare. Most authorities
      recommend that an HIV-positive health care worker be monitored by an expert
      panel, which could then, if necessary, refer to the regulatory body to revoke or
      restrict the person's license to practice. Mandatory HIV testing is not required
      for health care workers because they generally do not pose a risk for infecting
      their patients; they are, however, ethically and legally obligated to report
      their HIV status to their profession's regulatory body.

PMID- 11450217
TI  - Transfusion-transmitted babesiosis in Ontario: first reported case in Canada.
AB  - Babesiosis has only recently been reported in Canada, but a number of transfusion
      transmitted cases of this infection have been reported from the United States. We
      present a case of transfusion-transmitted babesiosis that occurred in Canada.
      Canadian physicians must consider babesiosis in the differential diagnosis of
      patients who experience fever or a hemolytic reaction after blood transfusion.
      Prompt recognition and treatment are important, because Babesia infections can be
      severe or fatal in certain risk groups. Better strategies to prevent transfusion
      transmitted babesiosis are required.

PMID- 11450218
TI  - Stem cell research gets nod, source of cells remains controversial.

PMID- 11450219
TI  - Bypass surgery or stenting for multivessel coronary artery disease?

PMID- 11450220
TI  - The cryptic nature of cryptosporidiosis.

PMID- 11450221
TI  - Particulate and soluble glycosaminoglycan-synthesizing enzymes. Preparation assay
      and use.

PMID- 11450222
TI  - Disaccharide composition of hyaluronan and chondroitin/dermatan sulfate. Analysis
      with fluorophore-assisted carbohydrate electrophoresis.

PMID- 11450223
TI  - Integral glycan sequencing of heparan sulfate and heparin saccharides.

PMID- 11450224
TI  - Analytical and preparative strong anion-exchange HPLC of heparan sulfate and
      heparin saccharides.

PMID- 11450225
TI  - Proteoglycans analyzed by composite gel electrophoresis and immunoblotting.

PMID- 11450226
TI  - Quantitation of proteoglycans in biological fluids using Alcian blue.

PMID- 11450227
TI  - Cellulose acetate electrophoresis of glycosaminoglycans.

PMID- 11450228
TI  - Disaccharide composition in glycosaminoglycans/proteoglycans analyzed by
      capillary zone electrophoresis.

PMID- 11450229
TI  - Purification of proteoglycans from mineralized tissues.

PMID- 11450230
TI  - Intact and oligomeric glycosaminoglycans analyzed with capillary electrophoresis.

PMID- 11450231
TI  - Recombinant expression of proteoglycans in mammalian cells. Utility and
      advantages of the vaccinia virus/T7 bacteriophage hybrid expression system.

PMID- 11450232
TI  - Purification of recombinant human decorin and its subdomains.

PMID- 11450233
TI  - Prokaryotic expression of proteoglycans.

PMID- 11450234
TI  - Proteoglycan gene targeting in somatic cells.

PMID- 11450235
TI  - Constitutive and inducible antisense expression.

PMID- 11450236
TI  - Cell-mediated transfer of proteoglycan genes.

PMID- 11450237
TI  - Purification of perlecan from endothelial cells.

PMID- 11450238
TI  - Morphological evaluation of proteoglycans in cells and tissues.

PMID- 11450239
TI  - Expression and characterization of engineered proteoglycans.

PMID- 11450240
TI  - Isolation of proteoglycans from cell cultures and tissues.

PMID- 11450241
TI  - Intracellular localization of engineered proteoglycans.

PMID- 11450242
TI  - Selection of glycosaminoglycan-deficient mutants.

PMID- 11450243
TI  - Xyloside priming of glycosaminoglycan biosynthesis and inhibition of proteoglycan
      assembly.

PMID- 11450244
TI  - Inhibition of heparan sulfate synthesis by chlorate.

PMID- 11450245
TI  - Detection of proteoglycan core proteins with glycosaminoglycan lyases and
      antibodies.

PMID- 11450246
TI  - Proteoglycan core proteins and catabolic fragments present in tissues and fluids.

PMID- 11450247
TI  - Degradation of heparan sulfate by nitrous acid.

PMID- 11450248
TI  - Isolation and characterization of nervous tissue proteoglycans.

PMID- 11450249
TI  - Degradation of heparan sulfate with heparin lyases.

PMID- 11450250
TI  - Degradation of chondroitin sulfate and dermatan sulfate with chondroitin lyases.

PMID- 11450251
TI  - In vitro assays for hyaluronan synthase.

PMID- 11450252
TI  - Hyaluronidase activity and hyaluronidase inhibitors. Assay using a microtiter
      based system.

PMID- 11450253
TI  - Detecting hyaluronidase and hyaluronidase inhibitors. Hyaluronan-substrate gel
      and -inverse substrate gel techniques.

PMID- 11450254
TI  - Affinity coelectrophoresis of proteoglycan-protein complexes.

PMID- 11450255
TI  - Analysis of proteoglycans and glycosaminoglycans from Drosophila.

PMID- 11450256
TI  - Binding constant measurements for inhibitors of growth factor binding to heparan
      sulfate proteoglycans.

PMID- 11450257
TI  - Interaction of proteoglycans with receptor tyrosine kinases.

PMID- 11450258
TI  - Measuring single-cell cytosolic Ca2+ concentration in response to proteoglycans.

PMID- 11450259
TI  - Serum amyloid A peptide interactions with glycosaminoglycans. Evaluation by
      affinity chromatography.

PMID- 11450260
TI  - Interactions of lipoproteins with proteoglycans.

PMID- 11450261
TI  - Hyaluronan and hyaluronan-binding proteins. Probes for specific detection.

PMID- 11450262
TI  - Novel confocal-FRAP analysis of carbohydrate-protein interactions within the
      extracellular matrix.

PMID- 11450263
TI  - Regulatory roles of syndecans in cell adhesion and invasion.

PMID- 11450264
TI  - Optical biosensor techniques to analyze protein-polysaccharide interactions.

PMID- 11450265
TI  - Phage display technology to obtain antiheparan sulfate antibodies.

PMID- 11450266
TI  - Cartilage and smooth muscle cell proteoglycans detected by affinity blotting
      using biotinylated hyaluronan.

PMID- 11450267
TI  - Tissue-specific binding by FGF and FGF receptors to endogenous heparan sulfates.

PMID- 11450268
TI  - Preparation of proteoglycans for N-terminal and internal amino acid sequence
      analysis.

PMID- 11450269
TI  - High-specific-activity 35S-labeled heparan sulfate prepared from cultured cells.

PMID- 11450270
TI  - Isolation of proteoglycans from tendon.

PMID- 11450272
TI  - Sports, exercise, and arthritis.

PMID- 11450271
TI  - Selective detection of sulfotransferase isoforms by the ligand affinity
      conversion approach.

PMID- 11450273
TI  - Canada's commitment to AIDS relief in Africa.

PMID- 11450274
TI  - Uncertainty about clinical equipoise.

PMID- 11450275
TI  - Uncertainty about clinical equipoise.

PMID- 11450276
TI  - The value of industry-sponsored studies of initial antihypertensive therapies.

PMID- 11450277
TI  - Lithotripsy comes to Ottawa ... at last.

PMID- 11450278
TI  - A time series would have been better.

PMID- 11450279
TI  - Preventive health care, 2001 update: should women be routinely taught breast self
      examination to screen for breast cancer?
AB  - OBJECTIVES: To evaluate the evidence relating to the effectiveness of breast self
      examination (BSE) to screen for breast cancer and to provide recommendations for
      routine teaching of BSE to women in various age groups as part of a periodic
      health examination. OPTIONS: Routine teaching of BSE to women. EVIDENCE: The
      electronic databases MEDLINE, PreMEDLINE, CINAHL, Health-STAR, Current Contents
      and the Cochrane Library were searched for abstracts and full reports of studies
      published from 1966 to October 2000 that evaluated the effectiveness of BSE in
      reducing breast cancer mortality. In addition, references of key papers were
      searched and experts consulted to ensure that all relevant articles had been
      identified. OUTCOMES: Prevention of death from breast cancer was viewed as the
      most important outcome; other outcomes examined included the stage of cancer
      detected, the rate of benign biopsy results, the number of patient visits for
      breast complaints, and psychological benefits and harms. VALUES: The
      recommendations of this report reflect the commitment of the Canadian Task Force
      on Preventive Health Care to provide a structured, evidence-based appraisal of
      whether a manoeuvre should be included in the periodic health examination.
      BENEFITS, HARMS AND COSTS: Breast cancer is the most frequently diagnosed cancer
      among Canadian women, accounting for 30% of all new cancer cases each year. In
      2000 an estimated 19,200 Canadian women would have been diagnosed with breast
      cancer, and 5500 would have died from the disease. To date, 2 large randomized
      controlled trials, a quasi-randomized trial, a large cohort study and several
      case-control studies have failed to show a benefit for regular performance of BSE
      or BSE education, compared with no BSE. In contrast, there is good evidence of
      harm from BSE instruction, including significant increases in the number of
      physician visits for the evaluation of benign breast lesions and significantly
      higher rates of benign biopsy results. RECOMMENDATIONS: Women aged 40-49 years:
      Because there is fair evidence of no benefit, and good evidence of harm, there is
      fair evidence to recommend that routine teaching of BSE be excluded from the
      periodic health examination of women in this age group (grade D recommendation).
      Women aged 50-69 years: Because there is fair evidence of no benefit, and good
      evidence of harm, there is fair evidence to recommend that routine teaching of
      BSE be excluded from the periodic health examination of women in this age group
      (grade D recommendation). The lack of sufficient evidence to evaluate the
      effectiveness of the manoeuvre in women younger than 40 years and those 70 years
      and older precludes making recommendations for teaching BSE to women in these age
      groups. The following issues may be important to consider: Women younger than 40
      years: There is little evidence for effectiveness specific to this group. Because
      the incidence of breast cancer is low in this age group, the risk of net harm
      from BSE and BSE instruction is even more likely. Women 70 years and older:
      Although the incidence of breast cancer is high in this group, there is
      insufficient evidence to make a recommendation concerning BSE for women 70 years
      and older. Important note: Although the evidence indicates no benefit from
      routine instruction, some women will ask to be taught BSE. The potential benefits
      and harms should be discussed with the woman, and if BSE is taught, care must be
      taken to ensure she performs BSE in a proficient manner. VALIDATION: The findings
      of this analysis were reviewed through an iterative process by the members of the
      Canadian Task Force on Preventive Health Care. The task force sent the final
      review and recommendations to 4 independent experts, and their feedback was
      incorporated in the final draft of the manuscript. SPONSORS: The Canadian Task
      Force on Preventive Health Care is funded through a partnership between the
      Provincial and Territorial Ministries of Health and Health Canada.

PMID- 11450280
TI  - Lower respiratory tract infections in Inuit infants on Baffin Island.
AB  - BACKGROUND: It has long been suspected that Canadian Inuit children suffer from
      frequent severe lower respiratory tract infections (LRTIs), but the causes and
      risk factors have not been documented. This study assessed the infectious causes
      and other epidemiologic factors that may contribute to the severity of LRTI in
      young Inuit children on Baffin Island. METHODS: A prospective case study was
      carried out at the Baffin Regional Hospital in Iqaluit, Nunavut, of infants less
      than 6 months of age, who were admitted to hospital between October 1997 and June
      1998 with a diagnosis of LRTI. Immunofluorescent antibody testing was used to
      identify respiratory viruses, and enzyme immunoassay (EIA) and polymerase chain
      reaction (PCR) were used to test for Chlamydia trachomatis. Demographic and risk
      factor data were obtained through a questionnaire. RESULTS: The annualized
      incidence rate of admission to hospital for bronchiolitis at Baffin Regional
      Hospital was 484 per 1000 infants who were less than 6 months of age; 12% of the
      infants were intubated. Probable pathogens were identified for 18 of the 27 cases
      considered in our study. A single agent was identified for 14 infants: 8 had
      respiratory syncytial virus, 2 adenovirus, 1 rhinovirus, 1 influenza A, 1
      parainfluenza 3 and 1 had cytomegalovirus. For 4 infants, 2 infectious agents
      were identified: these were enterovirus and Bordetella pertussis, adenovirus and
      enterovirus, cytomegalovirus and respiratory syncytial virus, and respiratory
      syncytial virus and adenovirus. C. trachomatis was not identified by either EIA
      or PCR. All infants were exposed to maternal smoking in utero, second-hand smoke
      at home and generally lived in crowded conditions. INTERPRETATION: Inuit infants
      in the Baffin Region suffer from an extremely high rate of hospital admissions
      for LRTI. The high frequency and severity of these infections calls for serious
      public health attention.

PMID- 11450281
TI  - Is it time to stop teaching breast self-examination?

PMID- 11450282
TI  - Creating a Canadian stroke system.

PMID- 11450283
TI  - Changing course in electronic seas: rapid publication of brief recommendation
      statements by the Canadian Task Force on Preventive Health Care.

PMID- 11450284
TI  - Antiretroviral therapy cannot be South Africa's first priority.

PMID- 11450285
TI  - Osler vindicated: the ghost of Flexner laid to rest.

PMID- 11450286
TI  - Humanitarian aid and medical research: an illusion of dichotomy in international
      health.

PMID- 11450287
TI  - Appropriate procedures for the safe handling and pathologic examination of
      technetium-99m-labelled specimens.
AB  - Technetium 99m may now be used to identify sentinel nodes for surgical excision
      in a growing number of cancer sites. The pathology specimens of these sentinel
      nodes and of any injected tumoural sites are radioactive. Consequently, specific
      clinical and laboratory procedures must be developed to handle these specimens
      safely. It is recommended that specimens containing the injection site should be
      quarantined for a period to permit decay of radioactivity. This quarantine does
      delay the reporting of pathology results to surgeons, oncologists and other
      clinicians, but it does not adversely affect final patient management.

PMID- 11450288
TI  - Assessing health technology assessment.

PMID- 11450289
TI  - Lifestyle changes can prevent the development of diabetes mellitus.

PMID- 11450290
TI  - Varicella vaccination. Recommendation statement from the Canadian Task Force on
      Preventive Health Care.

PMID- 11450291
TI  - The health impact of crowd-control agents.

PMID- 11450292
TI  - A wake-up call to CDA and provincial regulatory bodies.

PMID- 11450293
TI  - Privacy protection in the dental office. An interview with Dr. Richard Speers.
      Interview by Dr. John O'Keefe.

PMID- 11450294
TI  - Evidence-based dentistry: Part III. Searching for answers to clinical questions:
      finding evidence on the Internet.
AB  - The Internet is rapidly becoming a valuable source of information for all health
      care professionals, as well as for the consumers of health care--patients and
      their families and friends. Information on the Internet is uncontrolled and
      generally unevaluated. The quality filter of peer review, present in published
      dental journals, is usually lacking in Internet-based health sources. There are,
      however, a number of well-developed, highly-credible and useful resources
      available online that provide evidence-based information. In this paper, the
      third in a 6-part series on evidence-based practice, we discuss some of the sites
      that we have found to be most helpful for learning, teaching and practising
      evidence-based care.

PMID- 11450295
TI  - A rare complication of tooth abscess--Ludwig's angina and mediastinitis.
AB  - Deep neck infections are a rare but potentially fatal complication of pulpal
      abscess of the teeth. If an infection can progress rapidly from a toothache to a
      life-threatening infection, then it is critical that dentists be able to
      recognize the danger signs and identify the patients who are at risk. This
      article reviews a case of a seemingly innocuous toothache which rapidly
      progressed to Ludwig's angina and mediastinitis, and discusses how to recognize
      and manage these life-threatening infections.

PMID- 11450296
TI  - Oral manifestations of Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome is a rare hereditary disease of the connective tissue
      which can present oral manifestations. A brief history of the disease is
      presented along with the epidemiology and characteristics of the 8 main
      phenotypes of the syndrome. The article also describes the case of a 12-year-old
      patient presenting with hypermobility of the temporo-mandibular joint and
      capillary fragility, and highlights the precautions to take when treating
      patients with this syndrome.

PMID- 11450297
TI  - Diagnostic challenge. CAOMR challenge no. 2. Periapical cemental dysplasia.

PMID- 11450298
TI  - Chemokines and viral diseases of the central nervous system.

PMID- 11450299
TI  - Regulation of T cell responses during central nervous system viral infection.

PMID- 11450300
TI  - Virus-induced autoimmunity: epitope spreading to myelin autoepitopes in Theiler's
      virus infection of the central nervous system.
AB  - Epidemiological studies indicate that host immunogenetics and history of
      infection, particularly by viruses, may be a necessary cofactor for the induction
      of a variety of autoimmune diseases. To date, however, there is no clear-cut
      evidence, either in experimental animal models or in human autoimmune disease,
      that supports either molecular mimicry (Wucherpfennig and Strominger, 1995;
      Fujinami and Oldstone, 1985) or a role for superantigens (Scherer et al., 1993)
      in the initiation of T cell-mediated autoimmunity. In contrast, the current data
      provide compelling evidence in support of a major role for epitope spreading in
      the induction of myelin-specific autoimmunity in mice persistently infected with
      TMEV. It is significant that two picornaviruses closely related to TMEV,
      coxsackievirus (Rose and Hill, 1996) and encephalomyocarditis virus (EMCV) (Kyu
      et al., 1992), have been similarly shown to persist (either the viral RNA or the
      infectious virus) in their target organs and have been associated with the
      development of chronic autoimmune diseases, including myocarditis and diabetes.
      Thus, inflammatory responses induced by viruses that trigger proinflammatory Th1
      responses, and have the ability to persist in genetically susceptible hosts, may
      lead to chronic organ-specific autoimmune disease via epitope spreading. Epitope
      spreading has important implications for the design of antigen-specific therapies
      for the potential treatment of MS and other autoimmune diseases. This process
      indicates that autoimmune diseases are evolving entities and that the specificity
      of the effector autoantigen-specific T cells varies during the chronic disease
      process. Our experiments employing tolerance in R-EAE clearly indicate that
      antigen-specific treatment of ongoing disease is possible for preventing disease
      relapses, provided the proper relapse-associated epitope is targeted (Vanderlugt
      et al., 1999). However, the ability to identify relapse-associated epitopes in
      humans will be a difficult task because immunodominance will vary in every
      individual. The use of costimulatory antagonists that can induce anergy without
      requiring prior knowledge of the exact epitopes (Miller et al., 1995b), or the
      use of therapies that induce bystander suppression (Nicholson et al., 1997;
      Brocke et al., 1996), may thus be more practical current alternative therapies
      for the treatment of human autoimmune disease.

PMID- 11450301
TI  - Selection of and evasion from cytotoxic T cell responses in the central nervous
      system.

PMID- 11450302
TI  - DNA immunization and central nervous system viral infection.

PMID- 11450303
TI  - Transmissible spongiform encephalopathies and prion protein interconversions.

PMID- 11450304
TI  - Genetic determinants of neurovirulence of murine oncornaviruses.

PMID- 11450305
TI  - Spongiform encephalopathies: insights from transgenic models.

PMID- 11450306
TI  - The blood-brain barrier and AIDS.

PMID- 11450307
TI  - Neuroimmune and neurovirological aspects of human immunodeficiency virus
      infection.
AB  - Like most lentiviruses, HIV-1 causes both immune suppression and neurological
      disease. Neurological disease may occur at any stage of HIV infection but is most
      apparent with severe immune suppression. Cognitive impairment, reflected
      strikingly by HIV-associated dementia, has attracted intense interest since the
      outset of the HIV epidemic, and understanding of its pathogenesis has been
      spurred on by the emergence of several hypotheses outlining potential pathogenic
      mechanisms. The release of inflammatory molecules by HIV-infected microglia and
      macrophages and the concurrent neuronal damage play central roles in the
      conceptualization of HIV neuropathogenesis. Many inflammatory molecules appear to
      contribute to the pathogenic cascade and their individual roles remain undefined.
      At the same time, the abundance of virus in the brain and the type or strain of
      virus found in the brain may also be important codeterminants of neurological
      disease, as shown for other neurotropic viruses. Coreceptor use by HIV found in
      the brain appears to closely mirror what has been reported in systemic
      macrophages. The impact of HAART on viral genotype and phenotype found in the
      brain, and its relationship to clinical disease, remain uncertain. Several
      interesting animal models have been developed, using other lentiviruses,
      transgenic animals, and HIV-infected SCID mice, that may prove useful in future
      pathogenesis and therapeutic studies. Despite the progress in the understanding
      of HIV neuropathogenesis, many questions remain unanswered.

PMID- 11450308
TI  - Pseudorabies virus neuroinvasiveness: a window into the functional organization
      of the brain.

PMID- 11450309
TI  - Simian immunodeficiency virus model of HIV-induced central nervous system
      dysfunction.

PMID- 11450310
TI  - Neuroendocrine-immune interactions during viral infections.

PMID- 11450311
TI  - Role of viruses in etiology and pathogenesis of multiple sclerosis.

PMID- 11450312
TI  - Bornavirus tropism and targeted pathogenesis: virus-host interactions in a
      neurodevelopmental model.
AB  - Animal models provide unique opportunities to explore interactions between host
      and environment. Two models have been established based on Bornavirus infection
      that provide new insights into mechanisms by which neurotropic agents and/or
      immune factors may impact developing or mature CNS circuitry to effect complex
      disturbances in movement and behavior. Distinct losses in DA pathways in the
      adult infection model, and the associated dramatic movement disorder that
      accompanies it, make it an intriguing model for tardive dyskinesia and dystonic
      syndromes. The neuropathologic, physiologic, and neurobehavioral features of BDV
      infection of neonates indicate that it not only provides a useful model for
      exploring the mechanisms by which viral and immune factors may damage developing
      neurocircuitry, but also has significant links to the range of biologic,
      neurostructural, locomotor, cognitive, and social deficits observed in serious
      neuropsychiatric illnesses such as autism.

PMID- 11450313
TI  - Paradigms for behavioral assessment of viral pathogenesis.

PMID- 11450314
TI  - Neurovirology and developmental neurobiology.

PMID- 11450315
TI  - The use of echocardiography in the critical care setting.
AB  - Echocardiography has become an invaluable tool in the management of critically
      ill patients. Its safety and portability allow for use at the bedside to provide
      rapid, detailed information regarding the cardiovascular system. Echocardiography
      can elucidate cardiac structure and mechanical function. Recently, the power of
      clinical echocardiography has been augmented by the use of Doppler techniques to
      evaluate cardiovascular hemodynamics. An in-depth understanding of the proper use
      of echocardiography is a prerequisite for the intensivist.

PMID- 11450316
TI  - The pulmonary artery catheter: uses and controversies.
AB  - The pulmonary artery catheter is an invasive hemodynamic monitor that can provide
      diagnostic information in situations where history and physical examination are
      inconclusive. Assisting the physician in therapeutic decisions has added to its
      clinical value. Understanding the information it provides and making thoughtful
      therapeutic decisions lie at the core of its use. Despite its use, the PA
      catheter has been the center of great controversy. Clearly the paucity of
      prospective randomized trials proving its efficacy is alarming. The inability of
      physicians to interpret the provided data properly is also unacceptable. Although
      instituting a moratorium on its use may be extreme, limiting its use to approved
      indications seems more appropriate. In the future, ready availability of other
      less invasive methods such as echocardiography may allow clinicians to become
      less reliant on the PA catheter. Until then, clinicians would be served best by
      comprehending the intricacies and the limitations of this sophisticated
      instrument.

PMID- 11450317
TI  - Telecardiology and the intensive care unit.
AB  - Technology continues to advance at a pace that produces a new innovation daily.
      To move forward, clinicians must assess these potential technological solutions
      adequately for their clinical, financial, and customer satisfaction efficacies.
      Whether the payers, the patients, or health care will find these systems
      acceptable has yet to be established completely. The preliminary data in the
      literature seem to point to physicians' trepidations as the limiting factor. More
      work is needed on the legal and ethical issues surrounding telemedicine.
      Telemedicine is progressing quickly from a strange rare subtype of medicine into
      something that is part and parcel of the practice of medicine in general.
      Cardiology and intensivist practices have been impacted directly by this
      technology. As it matures it will be intertwined with daily practice.

PMID- 11450318
TI  - New developments in percutaneous coronary intervention.
AB  - The field of percutaneous coronary intervention continues to progress at a
      tremendous rate. Advances in techniques, in device technology, and in adjunctive
      therapy have increased significantly the number of patients who may benefit from
      angioplasty and have increased the early and long-term success rates of these
      procedures. Future progress in radiation therapy, IIb/IIIa inhibitors, stent
      design, and other novel approaches undoubtedly will offer further improvements in
      the capability of coronary interventions to help patients live longer and feel
      better.

PMID- 11450319
TI  - Management of acute heart failure exacerbation.
AB  - Patients with decompensated heart failure should be managed in an aggressive and
      proactive manner, using predominantly hemodynamic and end-organ function goals.
      This management is in contrast to the chronic maintenance therapy of patients
      with heart failure, where a neuroendocrine approach is indicated. Underlying
      anatomic targets for intervention should be sought aggressively and addressed.
      Patients who prove resistant to standard measures should be considered for early
      referral to heart transplant centers for more definitive measures, including
      evaluation for heart transplantation and mechanical circulatory support if
      necessary.

PMID- 11450320
TI  - Advances in cardiac electrophysiology and pacing.
AB  - Significant advances have been made in the management of cardiac arrhythmias. New
      technology has enhanced the ability to understand and treat a variety of
      tachycardias. Excitement and caution surround ablative approaches for atrial
      fibrillation. The role of ICDs and class III antiarrhythmic drugs in the
      management of patients at risk for sudden cardiac death has been clarified. A new
      indication for cardiac pacing is evolving as a supplemental treatment for
      patients with refractory congestive heart failure. These and other advances
      provide numerous exciting options for management of cardiac patients.

PMID- 11450321
TI  - The use of antiplatelet agents in acute cardiac care.
AB  - Antiplatelet therapy with aspirin has long been established as standard therapy
      in the management of conditions such as ST-elevation myocardial infarction and
      the acute coronary syndromes (unstable angina and non-ST-elevation myocardial
      infarction). Recently, several more potent platelet inhibitors have been
      developed and tested in randomized clinical trials. This article reviews the
      current state of the art of antiplatelet therapy.

PMID- 11450322
TI  - Antithrombotic and thrombolytic therapy in acute cardiac care.
AB  - This article explores the use of antithrombotic and thrombolytic therapy in acute
      cardiac care, and looks at traditional anticoagulant agents, newer antithrombin
      agents, thrombolytic agents, and others.

PMID- 11450323
TI  - Cardiogenic shock.
AB  - Mortality rates in patients with cardiogenic shock remain frustratingly high. Its
      pathophysiology involves a downward spiral in which ischemia causes myocardial
      dysfunction, which in turn worsens ischemia. Areas of viable but nonfunctional
      myocardium can contribute to the development of cardiogenic shock. Rapid
      diagnosis and prompt initiation of supportive therapy to maintain blood pressure
      and cardiac output, followed by expeditious coronary revascularization, are
      crucial. The SHOCK multicenter randomized trial has provided important new data
      that support a strategy of emergent cardiac catheterization and revascularization
      with angioplasty or coronary surgery when feasible. This strategy can improve
      survival and represents standard therapy at this time. In hospitals without
      direct angioplasty capability, stabilization with IABP and thrombolysis followed
      by transfer to a tertiary care facility may be the best option.

PMID- 11450324
TI  - The contemporary management of acute myocardial infarction.
AB  - The contemporary management of acute myocardial infarction continues to evolve
      rapidly. The ultimate goal of therapy is timely, complete, and sustained
      myocardial reperfusion. There is a powerful time-dependent effect on mortality,
      and thus the balance between the time and likelihood of maximal reperfusion is
      crucial in deciding whether to use primary percutaneous balloon angioplasty or
      thrombolysis as the initial reperfusion strategy. Newer thrombolytic agents allow
      for equivalent coronary reperfusion compared with the standard accelerated
      alteplase (tPA) regimen with the advantage of easier dosing regimens. Low
      molecular weight heparin has been shown to be superior to unfractionated heparin
      and likely will be the standard of care in the near future. The use of
      glycoprotein IIb/IIIa inhibitors has been shown to decrease the short- and long
      term complication rates in patients with acute coronary syndromes treated
      medically and with percutaneous coronary interventions; however, the choice of
      the optimal agent and dosing regimen in various clinical settings remains
      controversial. Combination therapy with low-dose fibrinolytics, glycoprotein
      IIb/IIIa inhibitors, and low molecular weight heparin, with or without subsequent
      early planned percutaneous coronary interventions, may provide the optimal
      strategy for maximal coronary reperfusion, but the results of large, randomized
      mortality trials currently underway need to be analyzed. Risk stratification will
      continue to play a major role in determining which patients should receive a
      specific therapy. The care of the patient with an acute myocardial infarction
      will continue to be a challenge requiring the proper selection from the vast
      pharmaceutic and interventional options available.

PMID- 11450325
TI  - Hypertensive emergencies.
AB  - In summary, patients presenting with a true hypertensive emergency should be
      diagnosed quickly and promptly started on effective parenteral therapy (typically
      nitroprusside 0.5 microgram/kg/min or fenoldopam 0.1 microgram/kg/min) in an
      intensive care unit. Blood pressure should be reduced about 25% gradually over 2
      to 3 hours. Oral antihypertensive therapy (often with an immediate-release
      calcium antagonist) can be instituted after 6 to 12 hours of parenteral therapy,
      and consideration should be given to secondary causes of hypertension after
      transfer out of the intensive care unit. Because of advances in antihypertensive
      therapy and management, "malignant hypertension" should be truly malignant no
      longer.

PMID- 11450326
TI  - Severe pulmonary hypertension: critical care clinics.
AB  - Pulmonary hypertension has many causes and therapies. A meticulous evaluation is
      critical. Substantial advances in medical therapy have occurred over the past
      decade, and the future treatment of this syndrome is promising, with many new
      medications on the horizon.

PMID- 11450327
TI  - Metabolic modulation of acute myocardial infarction.
AB  - Acute myocardial infarction continues to be the major determinant of death and
      disability in Western countries. Despite large improvements in management during
      the last 20 years, its high morbidity and mortality rates provide a stimulus to
      search intensively for different and widely applicable therapeutic options.

PMID- 11450328
TI  - Clinical toxicology in Krakow--Department of Clinical Toxicology: 35 years of
      activity.

PMID- 11450329
TI  - Poison information centers save lives ... and money!
AB  - Poison information centers provide telephone advice on the treatment of
      poisonings to the lay public and medical professionals. In general, the services
      of a poison center are provided freely to the caller. However, poison center
      services are labor intensive and expensive since most poison centers utilize
      medical professionals to provide service and are available for consultation 24
      hours/day. The failure of poison centers to produce revenue has made them
      vulnerable to closure. Poison centers provide a vital service to society by
      reducing morbidity and mortality. Often overlooked are the financial benefits of
      poison centers. By preventing unnecessary hospital admissions and by providing
      expert advice that may reduce the use of expensive antidotes and lengthy hospital
      admissions, poison centers save an estimated $6.50 for every dollar invested in
      their operation. The cost-effectiveness of poison centers is supported by a
      multitude of research. All entities that benefit from poison center services
      should assist in the financial support of poison centers.

PMID- 11450330
TI  - The critical role of the Poison Center in the recognition, mitigation and
      management of biological and chemical terrorism.
AB  - Nuclear, biological and chemical (NBC) terrorism counter measures are a major
      priority with healthcare providers, municipalities, states and the federal
      government. Significant resources are being invested to enhance civilian domestic
      preparedness through training in anticipation of a NBC terroristic incident. The
      key to a successful response, in addition to education, is integration of efforts
      as well as thorough communication and understanding the role that each agency
      would play in an actual or impending NBC incident. In anticipation of a NBC
      event, a regional counter-terrorism task force was established in southwestern
      Pennsylvania to identify resources, establish responsibilities and coordinate the
      response to NBC terrorism. Members of the task force include first responders,
      hazmat, law enforcement (local, regional, national), government officials, health
      departments, the statewide emergency management agency and the regional poison
      information center. The poison center is one of several critical components of a
      regional counter-terrorism response force. It can conduct active and passive
      toxicosurveillance and identify sentinel events. To be responsive, the poison
      center staff must be knowledgeable about biological and chemical agents. The
      development of basic protocols and a standardized staff education program is
      essential. The use of the RaPID-T (R-recognition, P-protection, D-detection, T
      triage/treatment) course can provide basic staff education for responding to this
      important but rare consultation to the poison center.

PMID- 11450331
TI  - New possibilities in scintigraphy detection of carbon monoxide cardiotoxicity.
AB  - The blood clearance of Tc99m MIBI is rapid and biexponential, with an initial
      fast phase followed by a slow phase. The fundamental myocellular uptake mechanism
      involves passive distribution across plasma and mitochondrial membranes, and at
      equilibrium, sestamibi is sequestered within the mitochondria by the larger
      negative mitochondrial transmembrane potential. Reverse distribution into blood
      stream is stopped by the high membrane potential of the cardiac cells.
      Scintigraphic changes followed by the metabolic abnormalities in patients after
      acute carbon monoxide poisoning can be necrosis or only the transitory ischemia.
      It seems to detect accurately the extension of the early necrosis (unreversible)
      of the myocardium. Amiscan kit for the preparation of Tc99m-glucarate is being
      developed as a radiopharmaceutical diagnostic agent for the imaging of and
      diagnosis of acute myocardial necrosis. Cellular and subcellular uptake studies
      have shown that Tc99m-glucarate localizes in necrotic tissues binding primarily
      to the nucleoprotein sub-fractions and to a lesser extent to the DNA fractions.
      Glucarate is taken up rapidly by necrotic myocardium and cleared relatively
      rapidly from the circulation resulting in early, hight target-to-background
      ratios. In studies of Amiscan in patients with acute myocardial infarction,
      sensitivity was found to be 100% when Amiscan is administered within 9 hours of
      the onset of chest pain. In our preliminary study the scintigraphic scans using
      Tc99m-glucarate were performed in 10 patients after acute carbon monoxide
      poisoning. The study can confirm that some patients during acute CO poisoning
      have typical myocardial necrosis, but part of them have hibernating and/or
      stunned myocardium.

PMID- 11450332
TI  - [Drugs an potential nephrotoxic substances].
AB  - The authors present potentially nephrotoxic medications most often employed in
      clinical practice, along with chemical substances and foods that may result in
      kidney damage. The possible nephrotoxic effect of certain plant and venom of
      certain animals is emphasized.

PMID- 11450333
TI  - [Cardiovascular disturbances in acute poisoning--mechanisms and management].
AB  - The authors present the most common in clinical toxicology cardiovascular
      disturbances and mechanism of action the selected drugs (tricyclic
      antidepressants, cardiac glycosides, beta-blocking agents and calcium channel
      blockers). General management in acute poisoning with these drugs is also
      presented, concerning their toxicodynamics.

PMID- 11450334
TI  - [Alcohol and the skin].
AB  - The cutaneous changes typical of patients, who are alcohol misusers have been
      reported in this study. We discuss also certain skin disorders which seem to be
      affected by alcohol misuse. We made an attempt to explain the ways of the
      influence of alcohol on mentioned skin diseases. It seems some skin disorders may
      be markers of alcohol misuse. Physicians who see patients with these particular
      diseases should be aware that there is a greater chance a patient is also an
      alcoholic. This additional risk factor needs to be considered when physicians
      design a treatment strategy.

PMID- 11450335
TI  - Environmental pollutants and allergy diseases.
AB  - A rapid increase in the prevalence of allergic diseases of our times as well as a
      significant increase in the IgE production in our population cannot be explained
      only by the genetic influence. Allergy is a growing, special problem of the
      industrial regions and well developed countries. The environmental factors and
      style of life seem to be the most important reasons of this phenomenon. The
      environment in which we live is full of natural and manmade substances capable of
      causing reactions in susceptible individuals. Xenobiotic--unnatural substances
      which appeared in polluted environment and act on our immunity may induce the
      suppression of it and in this way provoke the infection or neoplastic diseases.
      They may also induce the hyper-reactivity reaction and then become the reason of
      allergic or autoagression diseases. We distinquish two types of environmental
      pollution. Type I--with a high level of SO2 which induce infections and the
      chronic inflammation as a consequence of their irritants and a toxic action and
      type II pollutants (NOx, O3, VOC--volatile organic chemicals) which promote
      allergic diseases. The allergy in polluted areas additionally is accompanied very
      often by pseudo-allergy and toxic reactions. In order to stop the present
      increasing trend of allergic diseases we must increase our attempts to control
      allergens and irritants. There is no doubt today that the development of allergic
      diseases is related to the genetic predisposition and environmental factors.

PMID- 11450336
TI  - [Legal regulation dealing with the problem of drug addiction in Poland and on a
      comparative note].
AB  - The present paper introduces regulation of law obligatory in the modern world,
      with a view of preventing and fighting against drug addiction. It allowed to
      chart approximately the entire spectrum of possible and obeyed rules in the
      world. Amongst it the activity of international organisations was considered. A
      special attention was given to Polish legislation. Also the Law about prevention
      from Drug Addiction (31st January 1985) and law about Counteract against Drug
      Addiction (24th April 1997) were particularly regarded. A lot of effort was made
      to bringing the problem of drug addiction and delinquency forward, based upon
      Polish legislation.

PMID- 11450337
TI  - [Toxicological evaluation of diagnostic methods used for poisoning with
      psychoactive substances].
AB  - Toxicological diagnosis in cases of intoxication with psychoactive substances
      known in clinical and forensic toxicology requires appropriate laboratory
      studies. The paper pertains evaluation of the currently employed techniques of
      quantitative and qualitative analysis of psychoactive substances in a biological
      material. Usefulness of the most frequently applied screening (immunochemical)
      approaches and the confirmation (physicochemical) techniques was evaluated
      against the validation criteria, relating to the specificity, detection limit and
      sensitivity of the discussed substances.

PMID- 11450338
TI  - [Empirical basis for breaking the tobacco smoking habit].
AB  - Tobacco smoking generally regarded as a form of nicotine dependence. The
      behavioural effects of nicotine and its relative reinforcing properties, as well
      as the development of tolerance and withdrawal syndrome indicate that nicotine
      has addiction liability, which is however not strongly marked. Nicotine
      replacement therapy, low nicotine smoke aerosol and citric acid aerosol as
      potential smoking cessation aids are discussed.

PMID- 11450339
TI  - Envenoming by European vipers antivenom treatment--influence on morbidity.
AB  - The incidence of venomous viper bites in Europe is difficult to assess. Mortality
      after bites by European vipers is nowadays low, but morbidity is by no means
      negligible. Serious and life-threatening reactions occur, especially in small
      children and elderly people. The critically ill can nowadays be managed with
      symptomatic and supportive care in an astonishing way, but antivenom treatment
      may reduce the extent of such treatment and also reduced the overall risk for the
      patient. In particular, the only way to prevent extensive swelling and related
      complications is to give antivenom. The aim of this study was to test efficacy
      and safety of ovine Fab (a new specific ovine Fab fragments against various snake
      venoms) as an alternative to equine F(ab)2 antibodies in patients presenting with
      moderate and severe envenoming.

PMID- 11450340
TI  - Drug therapy: safety, effectiveness, and economics.
AB  - The problems of safety, effectiveness and economics of a drug therapy are
      discussed. Adverse drug reactions (ADR) represent not only a humanistic problem
      but also an epidemiological and economic one. The incidents and costs of ADRs are
      described, as well as pharmacovigilance and pharmacoeconomics as a tool of
      rationalizing the expenditures on health care.

PMID- 11450341
TI  - [Gene therapy in chronic heart failure--hopes and fears].
AB  - The article presents current views on the possibility of the applying of the gene
      therapy for advanced heart failure treatment. The gene therapy which offers a
      completely new treatment of this disease, but it requires a lot of many further
      efforts in development of gene-transfer vectors, gene-delivery techniques and new
      target genes identification.

PMID- 11450342
TI  - Drugs of abuse--an analysis based on cases from the Krakow Department of Clinical
      Toxicology of Jagiellonian University College of Medicine in 1997-2000.
AB  - The aim of the study was to present the frequency of acute drug overdosing by
      dependent patients in the years 1997, 1998, 1999 and 2000, and to compare the
      numbers of poisoned addicts suffering withdrawal syndrome and seeking
      detoxification. The analysis includes data for all drug addicts treated at the
      Krakow Department of Clinical Toxicology in years 1997, 1998, 1999 and 2000
      because of drug overdosing and resultant acute intoxication, because of
      withdrawal syndrome and also the opiate dependent patients qualified to methadone
      maintenance programme. The patients dependent on ethanol were excluded. A
      progressive increase in number of poisonings with psychoactive substances was
      noted in analysed years, respectively 231, 298, 331 and 442 patients. Drugs of
      abuse, were the most frequent cause of admission. Also incidence rate of
      poisoning expressed per 10,000 of Krakow inhabitants was highest for the cases
      admitted because of overdosing or craving for narcotics. Opiate derivatives
      produced at home from poppy straw or from juice of poppy head (so called "kompot"
      or "Polish heroin") were the most common cause of admission in all the analysed
      years: increase in number of acutely poisoned, and also increase in number of
      opiate dependent patients who suffered withdrawal syndrome and sought
      detoxification was noted in 2000 as compared to years 1998 and 1999. Opiate
      derivatives followed by amphetamine, as the single toxic agent or in mixed
      combinations, were still the most common drugs of abuse detected in body fluids.
      The men were dominant in all the analysed years, but the increase in number of
      depended women was observed through the years under analysis.

PMID- 11450343
TI  - The pattern of poisonings with substance of abuse in Poland (1997-1998).
AB  - Substances of abuse have been known in many cultures and geographic zones, and
      they were used for different reasons, from religions up to hedonistic ones.
      Central Europe, a region of Poland has never been an area of religious use of
      narcotics, but lately a number of drug abusers is still growing up. The extent of
      the drug abuse problem in Poland is difficult to assess, because there is no
      monitoring system, which registers drug abusers. In this study, authors
      retrospectively analyzed the files of all drug abuse poisoned patients treated in
      10 Polish Poison Centres; as well as the files of patients treated in other
      hospitals, but who were consulted by toxicologists from these units. During the
      last 10 years the number of patients treated for drug abuse intoxication has
      grown 10 times. The structure of used substance of abuse has also changed. In the
      early 90's opiates dominated. In 1997 all groups of drug abuses were noted, from
      natural or synthetic opiates, cocaine, LSD, amphetamine, up to Cannabis sativa
      derivatives (THC). We also revealed intoxications with hallucinogenic mushrooms
      and plant--Datura stramonium. The most common drugs used were opiates and
      amphetamine. THC were the third. Amphetamine and THC derivatives were the most
      often sources of intoxication in young people 15-25 years of age. The opiate
      poisonings were the commonest in young males, 20-40 years old.

PMID- 11450344
TI  - [Evaluation of health status in participants from a methadone treatment program
      in Krakow after one year of maintenance treatment].
AB  - Methadone treatment programme for 50 opiate addicts has been conducted at the
      Department of Clinical Toxicology for a one year. The aim of the study was to
      evaluate the health state including psychological condition and also a social
      status of the opiate dependent patients after one year methadone maintenance
      medication. Also, considering the results of clinical examination, a trial of
      elaboration of system for dependence scoring was undertaken. An improvement of
      general health state of addicts was observed. No new cases of HIV positive
      patients were noted. An increase in number of addicts who start professional
      activity, and those who live in procreative families and even in formally
      confirmed marriage. A three pregnant women, and five who already gave birth to a
      child (one of them is completely drug free at present) were noted. A significant
      behavioural changes, reduced level of criminal activity and restored personal
      relationships with family were observed. A moderate psychopathological symptoms
      are still observed in patients with double diagnosis.

PMID- 11450345
TI  - [Health status of individuals dependent on opiates before and after a year of
      treatment in a methadone maintenance program].
AB  - The aim of this study was to compare physical status of opiate dependent patients
      before and after one year of participation in the methadone maintenance program
      (MMP). There were investigated all 113 patients (82 male, 31 female)
      participating in MMP no shortly then one year. There was been used an especially
      constructed list of physical disorders and illnesses, where severity of them was
      scored from 0 to 3 points. We found a great influence of a participation in MMP
      on an use of forbidden substances, what caused that nobody of our patients
      overdosed drugs. Reducing of intravenous use of drugs and a change of lifestyle
      caused that nobody from our 67 HIV-negative patients infected with HIV. Thanks
      MMP was able the systematic and successful treatment of the most common physical
      illnesses: superficial venous system and skin infections, internal organs
      mycoses, lowered body mass index, lack of menstruation, and relatively rarer
      ones: hypertonia, sexually transmitted diseases, tuberculosis etc. The serious
      problem was liver impairments of different origin, in majority cases. IN
      CONCLUSION: MMPs should develop in Poland more quickly and more commonly.

PMID- 11450346
TI  - An evaluation of breathing nervous regulation of opiate dependent patients during
      in 6 months' methadone maintenance treatment programme.
AB  - During the methadone maintenance treatment an individually specified doses of
      methadone should prevent a withdrawal syndrome and may stabilise the activity of
      respiratory centres of opiate dependent patients. The aim of the study was to
      evaluate the direction of changes in respiratory pattern parameters of 34 opiate
      dependent patients (14 women and 20 men) during 6 months' methadone maintenance
      treatment at the Krakow Department of Clinical Toxicology. Respiratory pattern
      parameters and occlusion pressure were measured by means of a computer spirometer
      using "on line" during unrestrained breathing with atmospheric air. Examination
      of respiratory pattern were performed three times: I--initial examination--before
      administration of methadone maintenance treatment; II--control examination after
      3 months' methadone maintenance treatment; III--control examination after 6
      months' methadone maintenance treatment. An increase in values of occlusion
      pressure and minute ventilation were observed. The times of expiration and total
      times of inspiration-expiration cycle were shorter in III examination than in the
      examination before methadone administration. The values for the breathing cycle
      neuromuscular drive (VT/Tin) were relatively stable, but they were higher than
      those obtained in the control group. It may be related to the anxiety states and
      mood alteration. The largest individual variation in consecutive examination were
      observed for Tin/Ttot index being the timing component of respiratory patterns
      characteristic for parasympathetic control of breathing.

PMID- 11450347
TI  - The changes in spirometric measurements during 6 months' methadone maintenance
      treatment in opiate dependent patients.
AB  - The aim of the study was to evaluate the respiratory system response to
      individually specified doses of methadone in opiate dependent patients during 6
      months' methadone maintenance treatment at the Department of Clinical Toxicology
      CM UJ. There were 34 persons (14 women aged from 21 to 33 years and 20 men aged
      21-46 years) under examination. Examinations were performed three times: I-
      initial examination--before administration of methadone maintenance treatment; II
      -control examination after 3 months--methadone maintenance treatment; III-
      control examination after 6 months--methadone maintenance treatment. Ventilation
      efficiency was assessed on the basis of the results from a "flow-volume" loop,
      spirometry and the measurements of the respiratory tract resistance (Rrs) in a
      computerised system. Rrs was determined by means of the flow-interruption method.
      The parameters obtained from a "flow-volume" loop and spirometry were stabile
      within opiate substitution with methadone, whilst the values of respiratory
      resistance were significantly different. Significant increase in respiratory
      resistance values between initial and control examination (after 3 months) was
      noted. The normalisation of respiratory resistance was proved after 6 months
      treatment. It can indicate the impact of nervous component on spastic reaction of
      central bronchi.

PMID- 11450348
TI  - [Alcohol related hospitalization in the Department of Clinical Toxicology and
      Medicine Detoxification Ward of the Krakow Special Hospital of J. Babinski in
      Krakow].
AB  - The patients hospitalised because of acute ethanol intoxication or ethanol
      withdrawal syndrome at the Krakow Department of Clinical Toxicology and
      Detoxification Ward of J. Babinski Specialistic Hospital in the years 1997-2000
      were subjected to the study. A significant increase in number of ethanol related
      hospitalisation was noted at the Department of Clinical Toxicology (from 1381
      patients in year 1997 up to 1771 in year 2000), and at the Detoxification Ward of
      Babinski Hospital from 369 in 1997 and 849 patients in 2000 respectively. A
      significant increase in number of ethanol dependent patients admitted to the
      Department of Clinical Toxicology because of acute ethanol intoxication and the
      patients hospitalised because of ethanol withdrawal syndrome or signs of delirium
      tremens was noted. The same and even stronger trends in hospitalisation,
      particularly of those ethanol addicts presenting clinical symptoms of acute
      ethanol intoxication were observed at the Detoxification Ward of Babinski
      Hospital.

PMID- 11450349
TI  - [Diagnosis of ethanol dependence using the CAGE and SAAST questionnaire in
      selected therapeutic populations].
AB  - An diagnosing of ethanol dependence, despite of clear ICD 10 criteria, in
      patients treated particularly at the toxicological and detoxication wards, but
      also in other hospital wards is still a difficult task. Several questionnaires
      have been developed for easier detection of symptoms, the way of drinking and
      also for economic, family and medical effects of ethanol drinking in examined
      patients. A high sensitivity and specificity of CAGE and SAAST questionnaires
      allowing to identify problem drinkers or alcohol dependence in 192 patients of
      Krakow Department of Toxicology and 475 patients of Detoxification Unit was
      stated in the study. The CAGE questionnaire has allowed to identify the possibly
      ethanol dependence in group of 74 patients hospitalized at the Ward of Internal
      Diseases and Dialysis of Town Hospital in Sieradz, because of illness, that were
      not connected with alcohol drinking.

PMID- 11450350
TI  - [Evaluation of illicit drug use among students from universities in Gdansk].
AB  - Anonymous questionnaire examinations were performed among 1585 students from
      eight universities in Gdansk, including 664 men and 921 woman from 17 to 48 (mean
      21.4 +/- 2.26) years old. Illicit drugs were used by 45.9% of them, including
      33.7% applying sporadically. Since a large group of respondents (approx. 24%)
      used from two to seven narcotics, frequency of students' contacts with different
      narcotics, given below, was altogether higher than 45.9%. Women significantly
      less frequently than men were taken two or more illicit drugs (chi 2 = 69.4; p <
      0.0001). Cannabis was used by approx. 41% respondents (including about 29.8%
      applying sporadically), amphetamine by about 11% (including about 7.4% applying
      sporadically), LSD and magic mushrooms approx. 3.7% each, cocaine 1.1%. A few
      students took opium alkaloids, ecstasy, jimson-weed, and peyote. Men applied
      illicit drugs significantly more often than women did (chi 2 = 65.16; p <
      0.0001). Drug addicted students (approx. 1.4%) smoked more cigarettes and drunk
      more alcohol. The frequency of illicit drugs use was the highest among students
      from Academy of Fine Arts (about 70%), University School of Physical Education
      (about 58%) and Gdansk University (about 49%). Respondents of Priest Seminary
      have had no contacts with narcotics.

PMID- 11450351
TI  - [The evaluation of smoking and alcohol consumption by university students in
      Gdansk].
AB  - Anonymous questionnaire examination were performed among 1585 students from eight
      universities in Gdansk, including 664 men and 921 women from 17 to 48 (mean 21.4
      +/- 2.26) years old. Alcohol was consumed by 1452 (91.61%) students, including
      91.53% women and 91.72% men. Both men and women preferred beer, respectively,
      73.7% and 50.6%. In three-stage AUDIT-test (alcohol drinking dangerous to health)
      including 716 (45.2%) students, most of them in stage A (81.6%); in stage B about
      8.2% comprised while there were about 10.2% in stage C students. Alcohol
      consumption carried the lowest risk (stage A) among students of Medical
      University while corresponding risk was the highest among students of Maritime
      High School. Among respondents drinking alcohol dangerously to health there were
      significantly more persons who did drugs (73.7%). Students qualified to the AUDIT
      test smoked cigarettes significantly more often than the rest of the examined
      population. Smokers amounted to 399 (25.2%) students, including 224 (26.3%) women
      and 157 (23.6%) men. The difference in figures was statistically non-significant.
      Among smoking respondents the students of Fine Arts Academy constituted the
      majority, while those of Medical University and of University School of Physical
      Education were in minority. Catholic Priest Seminary respondents did not have the
      relevant experiences.

PMID- 11450352
TI  - [The kind of dependence and estimation of body mass].
AB  - The aim of the study was to evaluate frequency of overweight and underweight, and
      estimation of components of body mass (body fat, lean body mass, body water) in
      176 people: 61 men with aethanol dependency (group 1), 37 opiate addicted men
      (group 2), 32 men in control group (group 3), 14 opiate addicted women (group 4)
      and 32 women after first suicidal attempts who were treated in the Department of
      Clinical Toxicology (group 5). All of the patients had their Body Mass Index
      (BMI) calculated. The components of body mass were calculated using the method of
      bioelectrical impendance with Maltron. Statistical analysis was performed using
      the Statistica Software. The greatest differences were observed between group 2
      and group 1. In both groups more underweight, less overweight with less total
      body fat was observed, with the increase in body water. In both women groups no
      overweight or obesity were observed, but there were significant differences
      between various body components masses. Deficiencies in body fat were observed in
      86% women from group 4 and in 50% women from group 5. On the other hand excess of
      body water was observed in 93% from group 4 and only in 47% from group 5. Our
      studies shown that even among the persons with correct weight calculated using
      the BMI method some abnormalities can be observed in body fat, lean body mass and
      body water. We therefore conclude that only by measuring components of total body
      mass we may evaluate etiology of overweight and obesity.

PMID- 11450353
TI  - [Analysis of psychopathological symptoms in patients dependent on "Polish
      heroin", treated in the detoxification unit].
AB  - Thirty-nine "kompot" (Polish heroin) taking patients, diagnosed as opiate
      addicted, had been evaluated from psychological point of view. All of they were
      treated in the detoxification unit, Department of Clinical Toxicology in Krakow.
      Neuropsychological assessment was the main area of the psychological examination.
      Tests evaluating: memory, thinking, attention, learning and motivation were
      performed. Psychological observation was conducted too. It gave the possibility
      to complete the interpretation of neuropsychological tests' outcomes by quality
      behavioural analysis. It was also useful in developing and enhancement motivation
      to stay in treatment. To evaluate the personality of examined patients MMPI
      (Minnesota Multiphasic Personality Inventory) test was used. Outcomes of mental
      functioning exams showed that more than half of assessed patients had higher
      cognitive processes disturbances in different level. Examined dependencies follow
      that important for addiction level is the age when "kompot" taking occurred and
      this first of all concern the youngest patients.

PMID- 11450354
TI  - Determination of opiates in serum, saliva and hair addicted persons.
AB  - In the last ten years advances in analytical methods have enabled the
      determination of xenobiotics in alternative material such as sweat, saliva, and
      hair. The aim of this study was to develop an analytical method and measure the
      concentration of the main opiates in serum saliva and hair of subjects from a
      detoxification and methadone treatment programme. The analytical strategy in the
      presented study, based on enzymoimmunoassay screening of opiates in urine and
      GC/MS confirmation, meets the needs of forensic and clinical toxicology. Blood
      and saliva samples from thirty seven patients and hair from twenty three with a
      history of intravenous opiate use were collected for analysis. The ranges of
      morphine in serum and saliva were 0-2081 and 0-208 ng/ml respectively;
      corresponding concentrations of codeine were 0-580 and 0-428 ng/ml respectively.
      The concentration of morphine, codeine and 6-MAM in hair of addicts ranged
      respectively from 0-32.4, 0-12.5 and 0-2.8 ng/mg. From the clinical toxicology
      point of view, hair analysis is supplementary to urine, serum or saliva
      determination, but in drug testing at the workplace it can play a crucial role.

PMID- 11450355
TI  - Clinical and institutional aspects of antidote therapy in Russia.
AB  - The problem of antidote application for treatment of acute poisoning is related
      to epidemiology and characterization of poisoning cases, and possibilities for
      supplying antidotes to health care institutions. To investigate the situation in
      Russia we have analyzed reports by poisoning treatment centers for 1997-1999,
      comparison of medical aid standards for poisoning treatment in Russia with WHO
      recommendations. Acute poisoning pattern varies in different regions.
      Particularly, poisoning pattern in large cities in European Russia and the Urals
      is dominated by pharmaceuticals (up to 63.1%). Pesticide and insecticide
      poisoning cases do not exceed 1 to 2%, metal compounds and methemoglobin forming
      poisons (below 1% in each group). Antidotes are used in Russia in line with the
      recommendations adopted in international toxicological practice. The most actual
      are antagonists of opiates and benzodiazepines, physostigmine, atropine,
      pyridoxine, antagonists of beta-adrenergic blockers, activated charcoal. Such
      antidotes as DMPS (Unithiol), N-acetylcysteine, methylene blue, amyl nitrite (or
      sodium nitrite), complex formers of EDTA group are also included in the list of
      specific agents. The main problem is that some important antidotes are currently
      not produced in Russia. The Ministry of Health of the Russian Federation is
      taking efforts to launch production of some previously known and also newly
      developed important antidotes.

PMID- 11450356
TI  - Epidemiology and medical aid at acute poisoning in Russia.
AB  - The present study is based on the selected data obtained from medical reports by
      some Russian poisoning treatment centers, recent publications, statistical
      materials, and the review of the existing system of medical aid at acute
      poisoning. The number of acute poisoning cases in Moscow and large Russian cities
      has increased almost twofold in the last fifteen years. The main groups of toxic
      agents causing poisoning are pharmaceuticals (up to 63.1%), alcohol and
      surrogates (up to 49.3%), corrosives (up to 21.8%), although the figures vary in
      various Russian regions. Acute poisoning mortality in Russia tends to increase
      with about 56,000 in the recent years. The main causes of poisoning were alcohol
      (62.2%), carbon monoxide (15.4%), acetic acid (6.3%), pharmaceuticals (4%) (data
      by the Moscow Forensic Bureau). Specialized medical aid is represented by
      poisoning treatment centers organized in 37 cities, 1 toxicology information and
      advisory center of federal level. Physicians can advance their skills at post
      diploma courses organized at 4 chairs of clinical toxicology. Scientific research
      in the field is carried out by Moscow city poisoning treatment center, the
      abovementioned chairs and other interested institutions. To obtain the maximum
      complete data on the number, pattern and causes of acute poisoning a unified
      system for toxicological monitoring was introduced in Russia in 2000.

PMID- 11450357
TI  - Usefulness of rest and forced perfusion scintigraphy (SPECT) to evaluate
      cardiotoxicity in acute carbon monoxide poisoning.
AB  - The aim of the study was to evaluate myocardial perfusion in acute carbon
      monoxide poisoned patients using rest and stress Tc 99m-MIBI SPECT scintigraphy.
      There were 29 study patients (15 men and 14 women) aged from 14 to 46 years
      poisoned acutely with CO at home. Measurement of COHb, blood lactate level,
      duration of exposure and ECG examination were performed on admission to the
      Clinic. The enzymes activity (ALT, AST, CBK) were evaluated after 24 hours. The
      first rest Tc99m-MIBI SPECT was performed in all patients two to five days after
      intoxication. Fifteen of the patients underwent the control examination: stress
      and rest scintigraphy six months after CO exposure. Moving track exercise
      according to the Bruce protocol was used in each the patients. The control rest
      scintigraphy was performed 48 hours after exercise. Abnormal, differently
      intensified scans were noted in all the subjects: 5 patients had a I degree of
      pathological changes, 7 patients had II degree, 16--III degree and 1 patient had
      a IV degree of pathological changes. In 14 of the patients with pathological
      scintigraphic scans the normal EKG curves were noted. The mean COHb level was
      35.0 +/- 7.22%, the blood lactate concentration was 4.4 +/- 3.7 mmol/L. The
      average duration of exposure was 108.4 +/- 163.9 min. Effort related ischemia was
      not noted in 10 of the patients who underwent control examination. An improvement
      in rest scintigraphic scans was stated in 12, and no changes were observed in 3
      of the controlled patients. Deterioration was not found in any patient. No
      correlation between ECG results and scintigraphic image of myocardium was found.
      Tc 99m-MIBI SPECT scintigraphy is a more sensitive method than
      electrocardiography and measurement of enzymes activity for the evaluation of CO
      cardiotoxicity in acute poisoning. The method enables evaluation of the
      localization and disease extent.

PMID- 11450358
TI  - [Usefulness of enzyme tests, biochemical tests and ultrasonography for evaluation
      of hepatotoxic impact of ethanol].
AB  - The aim of this study was to evaluate the morphological and functional status of
      the liver in alcoholics using ultrasonography, measurements of chosen enzymes
      activity and biochemical parameters. The attempt to estimate the dependence of
      the frequency and intensification of the liver lesion on the controlled
      abstinence period was also made in this study. Under examination there were 30
      ethanol dependent patients, poisoned with ethanol, treated at the Department of
      Toxicology. In order to detect the dynamics of liver lesion all patients
      underwent second examination after 3 weeks of a controlled abstinence. The
      reference group comprised 30 healthy men, not exposed to hepatotoxic agents. The
      liver ultrasonography combined with biochemical analysis allows to assess the
      liver condition in alcoholics poisoned with ethanol.

PMID- 11450359
TI  - [Macroscopic and microscopic picture of the gastric mucosa in alcoholics].
AB  - The aim of the study was to compare a macroscopic and microscopic picture of the
      gastric mucosa of ethanol dependent patients admitted to the Krakow Department of
      Clinical Toxicology because of acute ethanol intoxications (n = 28) with those
      admitted because of ethanol withdrawal syndrome (n = 38). All the 66 study
      patients suffered from gastrointestinal tract symptoms. The mean age was 41.5 and
      mean duration of ethanol dependence was 10 years. The mean blood ethanol
      concentration in acutely intoxicated group was higher then 1 g/L, intensification
      of withdrawal syndrome in the group of non-acutely intoxicated patients was
      higher than 15 points according to CIWA scale. In the first day of
      hospitalization gastrointestinal endoscopy was performed and specimens from
      gastric corpus, antrial, and pyloric region mucosa were taken to
      histopathological examination. In 46 of still symptomatic patients a control
      gastroscopy and histopathological examination were performed after 10 days of
      controlled abstinence. A normal macroscopic picture of gastric mucosa was stated
      in 25% of acutely ethanol intoxicated patients and in 26% of those ethanol
      abusers who were admitted because of withdrawal syndrome. In 76% of all the
      examined patients a mild, superficial inflammatory changes localized mostly in
      distal part of the stomach were revealed by endoscopy. The symptoms of chronic
      inflammation and also the sings of inflammation's activity, mostly in antrum
      region, were revealed by histopathological examination in all the cases. The
      higher histopathological dynamics of inflammatory changes and higher
      inflammation's activity, mostly in the stomach distal part, were found in the
      patients suffering from ethanol withdrawal syndrome.

PMID- 11450360
TI  - The influence of lead and cadmium environmental pollution on anthropometric
      health factors in children.
AB  - THE AIM: The aim of the study was to examine the relationship between environment
      pollution (lead and cadmium) and selected anthropological factors. MATERIAL AND
      METHODS: The study group comprised 267 children, aged 11 +/- 0.4. Blood sampling
      and anthropological measurements were carried out in Krakow (polluted area) and
      in the Krosno region (low polluted area) in 1995. The lead and cadmium
      concentrations in the whole blood were determined using atomic absorption
      spectrometry with a graphite furnace and automatic dosage. The anthropometric
      measurements were made at the same time as the blood collection. RESULTS: The
      blood lead content in boys and girls was: 5.89 +/- 2.54, 5.01 +/- 1.62
      micrograms/dl respectively, and the cadmium blood content was: 0.65 +/- 0.30,
      0.68 +/- 0.47 microgram/l. Body mass and height did not correlate with lead and
      cadmium concentrations in the children's blood. Smaller head circumferences,
      independently of gender, were associated with a higher cadmium level. The values
      of four skin-folds (on the arm: biceps, triceps, under scapular bone and above
      iliac crest), as well as the percentage of fat content in the organism (PFDWB)
      calculated by the Slaughter-Lohman equation was higher in girls than in boys.
      CONCLUSIONS: 1. The relationships between cadmium and lead blood levels in
      children on the one hand and the degree of environmental pollution with these
      metals, and the gender of the children on the other were observed. The boys
      accumulated more lead, whereas the girls absorbed more cadmium. 2. Anthropometric
      analysis did not show a significant influence exerted by the polluted environment
      on the basic auxological parameters. In the group of children examined, the only
      differences observed were related to gender, head circumferences and indicators
      of obesity.

PMID- 11450361
TI  - [A trial for the complex risk assessment of repeated suicide predictors in
      patients after suicidal poisoning attempts, hospitalized in the Department of
      Clinical Toxicology CM UJ in Krakow. I. Influence of socio-demographic factors].
AB  - The study included 180 patients aged 18-79 (average 36) hospitalized for suicide
      attempts (drug intoxication) in Department of Clinical Toxicology CMUJ from March
      to December 2000. Examined group was composed of 49 men and 131 women. Structured
      investigation and medical documentation were used to estimate crucial socio
      demographic risk factors of repeated suicide attempt. The following socio
      demographic traits were taken into consideration in analysis: age, sex, marital
      status, place of living, education, employment, family background. We
      distinguished among patients under examinations: patients after first suicide
      attempt (I) and group after another suicidal attempt (II). The second group
      consisted of 15 men (27.8% of the total) and 39 women (72.2% of the total). Young
      people under 30 constituted 37.2% of the whole examined population. In population
      of women after repeated suicide attempt the percentage of divorced ones increased
      considerably (from 2.2% to 10.2%). Both in men and women after repeated suicide
      attempt the percentage of persons with only elementary education increased (from
      34.1% to 53.7%). We observed high unemployment rate (from 26.6% to 29.6%) in both
      groups. Percentage of pensioners increased from 23.5% after first suicidal
      attempt to 33.3% after repeated suicidal attempt in men and from 25.5% to 35.9%
      in women. Men after repeated suicide attempt more often live with their parents,
      while women from the second group more often live alone with their children. It
      seems that some of the analysed predictors which are expression of social
      unadjustment may make risk factor for repeated suicidal attempts.

PMID- 11450362
TI  - [A trial for the complex risk assessment of repeated suicide predictors in
      patients after suicidal poisoning attempts, hospitalized in the Department of
      Clinical Toxicology CM UJ in Krakow. II. Clinical predictors].
AB  - The study included 180 patients aged 18-79 (average 36) hospitalized for suicide
      attempts (drug intoxi-cations) in the Department of Clinical Toxicology CM UJ
      from March to December 2000. Examined group was composed of 49 men and 131 women.
      The following tests were used in this study: structured questionnaire,
      psychological tests: Beck Depression Inventory, Hamilton Depression Scale,
      Hopelessness Scale, Suicidal Intent Scale, Life Events Scale, SOC 29 (by
      Antonovsky). Besides, we used data from patients' history. The aim of our study
      is to analyse clinical data of suicidal attempters--after first and repeated
      suicidal attempts. We took into consideration the severity of coma, severity of
      intoxication, the kind of substances used in the attempt, the presence of
      alcohol, previous psychiatric treatment, cases of suicide among the patients'
      close friends or relatives and duration of hospitalization. Then the psychiatric
      diagnosis was stated. The analysis of severity of intoxication (divided into
      three stages: severe, moderate, and light according to the Poisoning Severity
      Score (PSS) indicated that in the group of repeated suicide attempters the
      percentage of severe intoxications was greater (9.2%) then in first time
      attempters. In the population of second time female attempters there is a greater
      percentage of persons who took neuroleptics (15.4%) compared to group first
      attempters (5.4%). In both groups the majority were taking anxiolytisc, sleep
      inducing and mixed drugs. There was a greater percentage of persons drinking
      alcohol during the attempt among repeated suicidal attempters (38.8%) than among
      the first time attempters (26%). The percentage of persons with diagnosis of
      mental disease (treated in ambulatory or in hospital) is higher in the group of
      repeated suicide attempters (25.9%) then after first attempters (6.3%). In both
      groups a lot of persons had reactive depression, often associated with
      personality disorders, rarely endogenic depressions or psychosis. We observed
      that addiction to alcohol is often a problem in men who attempt suicide (I group-
      32.3%, II group--33.3%). The analysis of medical documentation indicated in the
      group of repeated suicide attempters a high percentage of people with cases of
      suicide among their close friends or relatives.

PMID- 11450363
TI  - [The sense of coherence and risk of suicide attempt].
AB  - The analysis was based upon 79 patients hospitalized for suicide attempts (drug
      intoxication) in the Department of Clinical Toxicology CM UJ in Krakow from July
      to December 2000. The purpose of the study was to estimate the sense of coherence
      level (according to Antonovsky) as a potential suicide attempt predictor. The
      population of patients was divided into two groups: patients after first suicide
      attempt (I) and group after reattempting suicide (II). The examination was based
      on structure interview, analysis of medical documentation and a number of tests
      including SOC 29 (by Antonovsky), Beck Depression Inventory (BDI), Hamilton
      Depression Rating Scale (HDRS), and Beck Hopelessness Scale (HS 20). The most
      important psychological and independent variable measured in the study was the
      sense of coherence, introduced first by Aaron Antonovsky as a significant
      predictor of mental health. The sense of coherence (measured by SOC 29
      questionnaire) comprises comprehensibility, manageability and meaningfulness.
      Both in foreign and in polish studies the SOC 29 level was lower in clinical
      groups compared to healthy people. The norm in Polish population was 139 scores
      in SOC 29. In the present study the average total result (men and women) was 112
      scores in the group of patients after first suicide attempt, and in the group of
      repeated suicide attempters the average total result was even lower--only 99
      scores, which makes a statistically significant difference. We also observed a
      statistically significant dependence between the results of SOC 20 questionnaire,
      the level of depression measured by Beck Depression Inventory and Hamilton
      Depression Scale, and the level of hopelessness measured by Beck Hopelessness
      Scale. The above results indicate that the sense of coherence level may make
      significant risk factor for repeated suicide attempt.

PMID- 11450364
TI  - [Significance of subjective evaluation of life events as risk factors for
      predicting future suicide attempts].
AB  - Among the total population of 180 patients undergoing medical examination between
      March and December 2000, hospitalized for suicide attempts (drug intoxication) in
      the Department of Clinical Toxicology CM UJ in Krakow, 159 persons were examined
      by means of modified questionnaire of life events based on a scale elaborated by
      Thomas Holmes and Richard Rache. The patients were divided into 2 groups--first
      group comprised patients after first suicide attempt and second group consisted
      of those who had reattempted suicide. In regard to sex and age there were no
      significant differences between these two groups and the total population of 180
      patients. In order to obtain the patients' subjective evaluation of the influence
      of their course of life on their attempting suicide, we asked the patients to
      select from the list of life events those that had affected their mental and
      physical state during of whole their life. Objectivization of life events was
      based on the 'units of life change' by T. Holmes and R. Rache. The sum of units
      of life events was 373 scores (SD +/- 200, in the range of 39-1042 units). From
      the total list of life events (max. score--1513) we selected the events estimated
      at 40 and more units of life change. Those were; marriage, divorce, separation,
      marital reconciliation, patient's illness, change of behavior and illness of a
      close relative, death of a husband/wife, child, close relative, imprisonment,
      pregnancy, unemployment, retirement. In the patients' subjective evaluation part,
      the events most frequently selected by the patients as those that had affected
      their mental state were: death of a close relative (56.6%), illness of a relative
      (40.8%), patient's illness (37.7%). A high number of patients stated events
      testifying to a conflict in marriage--45.7% of patients stated marital
      separation, and reconciliation, and 27% of patients stated unemployment as a fact
      that had influenced their mental state. 30.6% of these patients belonged to the
      first group (after first suicide attempt) and only 18.7% belonged to the second
      group (after repeated attempt). The authors of the study have presented a
      discussion over the results of the analysis and demonstrated the need for
      cultural adaptation of so that it can be effectively used in General
      Practitioners' training.

PMID- 11450365
TI  - [Two complex suicidal poisonings with drugs and their medicolegal aspects].
AB  - The main subject of the study was a toxicological investigation of biological
      specimens coming from two cases of intoxication with mixture of drugs. Two young
      people decided to commit suicide by the use of mixture of drugs mainly analgesic
      in approximately equal doses. For one person the dose of drugs administered
      turned out to be fatal while second person survived with the symptoms of acute
      intoxication. The analysis carried out with the use of liquid chromatographic
      method with mass detection (HPLC/MS) confirmed the presence of mixture of drugs
      in blood of living person and in postmortem specimens of the victim in
      significant concentrations. The toxicological findings have delivered information
      for discussion in medico-legal and ethical aspects.

PMID- 11450366
TI  - The bacterial flora and the changes of the N-nitrosamine concentration in the
      operated stomach.
AB  - The studies included 170 patients (103 men and 67 women) aged 23 to 66 years,
      operated on because of an ulcerous disease. Depending on the method of surgical
      treatment patients were divided into 5 groups (those after gastric resection with
      Rydygier's method, after resection with the Billroth II method, after trunk
      vagotomy with pyloroplasty, after highly selective vagotomy, and after gastro
      enterostomy). In all patients a qualitative estimation of the nitrate-reducing
      bacteria was carried out, as well as a chromatographic test of the selected N
      nitrosamine concentration in the gastric juice. It was shown that the changes in
      the quantity of the nitrate-reducing bacteria and in the N-nitrosamine
      concentration depended on the type of surgical intervention conducted. The
      largest mean content of nitrate-reducing bacteria and the highest average N
      nitrosamine concentration were confirmed in the gastric juice of patients after
      gastroenterostomy and after gastric resection with the Billroth II method, and
      the lowest values--in patients after highly selective vagotomy.

PMID- 11450367
TI  - [Use of buprenorphine as a substitute treatment for opiate dependence in the
      Toxicology Clinics--introductory clinical report].
AB  - That the problem of drug addiction is still growing up, so there is the necessity
      for widen of treatment panel for psychoactive substances abuse, especially for
      opiates. Because of the fact, that substituting treatment became to be popular in
      patients' opinion, more attention were paid on new medicine-buprenorphine. It is
      an agonist- antagonist of opiates' receptors. Buprenorphine has been successfully
      used in long-term treatment in United States and in Western Europe. Treatment
      with buprenorphine has been started in Poland in Toxicological Department in
      Krakow. This article shows outcomes of substituting treatment with buprenorphine
      in period from December 2000 to February 2001.

PMID- 11450368
TI  - [Severe carbon monoxide poisoning: different clinical course--the same source of
      exposure].
AB  - The different course of acute carbon monoxide poisoning in two young people
      exposed to the same Carbon monoxide source are reported in the study. The
      pulmonary edema was diagnosed in the man, but not in the woman. The brain
      morphological changes revealed by MRI were significantly marked in the women
      compared to the intoxicated man. MRI detected the brain changes invisible in CT
      scans and seems be more useful for evaluation CNS abnormalities. The
      neuropsychological examination, of the brain functional changes is also necessary
      for proper evaluation of the CNS damage.

PMID- 11450369
TI  - [Guillain-Barre syndrome as a result of poisoning with a mixture of
      "kompot"(Polish heroin) and drugs].
AB  - Guillain-Barre Syndrome is the most common form of polineuropathy. It is
      suggested that some infectious, immune and allergic factors are involved in
      developing the syndrome. "Kompot" or "Polish heroine", a domestic product, is
      produced from poppy straw or juice of poppy head (Papaver somniferum) and it is
      administered intravenously. "Kompot" shows variable contents of heroine, 6-MAM, 3
      MAM, morphine, acetylo-codeine and codeine as well as papaverine, thebaine and
      narcotine. The case history of a young man dependent on "Polish heroine" who
      developed the Guillain-Barre Syndrome due to severe intoxication induced by home
      made heroine, barbiturates and benzodiazepines is described.

PMID- 11450370
TI  - [Clinical and biochemical aspects of accidental poisoning with tetraethyl lead in
      a 2.5 year old patient--long term observation].
AB  - The paper describes an accidental, acute toxic exposure of a 2.5-year-old girl to
      tetraethyl lead. The authors discuss the clinical picture and treatment within
      the acute phase of intoxication as well as during the ambulatory follow-up of
      chronic sequelae of the exposure. Systemic, periodic monitoring of lead (Pb)
      levels in the blood (B-Pb) and urine (U-Pb) over a 2-year period gave the authors
      a unique opportunity to observe the dynamics of urinary excretion of this
      element. In the acute phase of intoxication the Pb blood value reached the
      plateau at the 46 micrograms/dl after 3 days from the exposure. Mild
      encephalopathy and gastrointestinal tract irritation was observed at that time.
      After 3 weeks of hospitalisation Pb levels decreased to the values 32
      micrograms/dl whereas urinary Pb diminished from the initial 600 micrograms/L to
      56 micrograms/L. During the 2-years outpatient follow-up Pb in the blood
      decreased to 7 micrograms/dl. Urinary Pb is still maintained above the population
      value's range. No detectable, permanent detrimental health effects were observed
      in the child. The girl is followed-up in annual intervals. Several other tissues
      are and will be assessed by non-invasive methods (e.g. hair, primary teeth) and
      analysed for accumulated Pb. The collected data will allow the authors for
      describing Pb distribution in the body as well as long term excretion in the
      growing and developing organism of the child.

PMID- 11450371
TI  - [Toxic effects of baclofen in a patient with chronic renal insufficiency].
AB  - In this work the authors reported the case of a 29-year-old woman, who had been
      dialysed since 1997 in the course of chronic pyelonephritis caused by
      vesicoureteral reflux. Due to the detrusor vesica urinariay's hypofunction
      (confirmed by repeated urodynamic studies) the patient was prescribed Baclofen
      with a dosage of 2 x 10 mg per 24 hours. In the course of Baclofen's therapy,
      toxic effects of the drug like weakness, nausea, vomiting and fears appeared
      during the second day of treatment. They had been increasing since the patient's
      admission to the Dialysis Centre where she had immediately undergone the planned
      haemodialysis. After the initial increase of the poisoning symptoms including the
      loss of consciousness, patient's state of health improved after approximately two
      hours since the haemodialysis had been performed. After five more days in
      hospital, the patient was discharged in general good condition (two more planned
      haemodialyses were performed at the time of treatment).

PMID- 11450372
TI  - [Neuroleptic malignant syndrome--case report].
AB  - We have reported the case of a 65-year-old woman treated with neuroleptics
      because of organic delusive disturbances. She was treated for about one month
      with risperidone (Rispolept) and perazine (Pernazinum). Around ten days before
      the patient was admitted to this ward, the following had been observed: rise in
      temperature up to 40 degrees C, progressive weakness and blood pressure (RR)
      fluctuationis. Despite the applied treatment, the patient died during the fourth
      of hospitalization on this ward. The diagnosis of neuroleptic malignant syndrome
      was made on the basis of the clinical picture accomplished whole of biochemical,
      figurative tests as well as on the conducted differential diagnostics.

PMID- 11450373
TI  - [Toxic injury of the liver by augmentin in a 70-year old patient].
AB  - We are describing a case of undesired side effect of the cure (toxic
      hepatocellular damage) by Augmentin. The main symptoms were jaundice and
      pruritus. This is the next documented case of the hepatocellular damage by
      Augmentin in Poland. In the conclusion, we draw the attention to the role of
      interview in the diagnosis of the illness described and therapeutic management.

PMID- 11450374
TI  - [Pharmacokinetic and toxicokinetic parameters of some drugs of abuse].
AB  - This article outlines the main pharmacokinetic and toxicokinetic parameters of
      selected addicting compounds often being abused. Described parameters affect the
      way the compounds behave in the body. The article shows the usual dosage and
      "therapeutic", toxic and fatal concentrations. Knowledge of described parameters
      is important in the process of detoxication in patients poisoned with this group
      of psychoactive compounds.

PMID- 11450375
TI  - [Criminal contamination by metallic mercury of cow's silage].
AB  - This paper presents an unsuccessful homicidal attempt on 23 persons by means of
      metallic mercury added in large amount to cow's silage. Thirteen adults and
      twelve children used milk from these cows for 4.5 months. The mercury
      concentration in the milk of these cows as well as in serum and daily urine of
      consumers of the milk were examined by atomic absorption spectrophotometry.
      Despite the increased level of mercury in the milk (average 0.023 mg/kg), the
      concentrations of mercury in daily urine of only three persons were raised about
      50%. These people had been working in a cowshed without ventilation every day for
      many months and thus had been exposed to vaporised mercury.

PMID- 11450376
TI  - [Use of different drug form identification systems].
AB  - Since the foundation of the Department of Clinical Toxicology one of the unsolved
      problems is the identification of drugs which are often brought by the emergency
      service together with the patient. This problem is known to the personnel of
      Poison Centers and all first-contact physicians who deal with the patient at home
      or at the place of accident. Many years of observations and experiences allowed
      for creating Polish system of drugs identification based mainly on the catalogue
      containing data to be used in identification of an unknown form of a drug. The
      next step was to create a computer database system allowing for fast and accurate
      identification of drug forms. Created catalogue contains drug forms categorized
      by color and shape. The solution is constructed in a way that adding new and
      extending existing data is possible. The catalogue can be used in drug stores, by
      emergency services, family doctors and specifically in pediatrics since children
      are often exposed to the danger of unknown drug intake. The useful option is the
      color printout which can be obtained from the system. Search procedures enable
      setting range of criteria and, after initial list is produced, detailed search is
      possible with the color images on screen. The system was created using MS Access
      database. Department of Toxicology is the owner of the copyrights.

PMID- 11450377
TI  - Immunisation status of children in BIMARU states.
AB  - To assess the immunisation status of children in the states of Bihar, Madhaya
      Pradesh, Rajasthan and UP the evaluation covered BCG, DPT, OPV, Measles, Pulse
      Polio and Vitamin A. WHO 30 cluster survey methodology with certain modifications
      incorporating information on sex of the child, literacy of parents and distance
      of the village was used. Study covered 30 districts, 900 villages and 6300
      children. About 48 per cent of children received all the vaccines (BCG, DPT, OPV,
      Measles) in these states as compared to 63 per cent at All India level. These
      states accounted for about 70 per cent of non-immunised children. The coverage
      levels were lower for children of illiterate mothers and in small, inaccessible
      and triple villages. The literacy of mother is the key to the success of the
      Universal Immunisation Programme (UIP). Information, Education and Communication
      (IEC) activities should specially be targeted to educate the moters in rural
      areas. The underserved areas of these four states should have special focus in
      the programme and hence the tribal, small and inaccessible villages in the
      coverage should be focused and targeted, immediate improvement in the coverage
      could also be achieved by better follow-up and reducing drop-out rate.

PMID- 11450378
TI  - Surfactant replacement therapy--economic impact.
AB  - Surfactant replacement is an effective treatment for neonatal respiratory
      distress syndrome. (RDS). As widespread use of surfactant is becoming a reality,
      it is important to assess the economic implications of this new form of therapy.
      A comparison study was carried out at the Neonatal Intensive Care Unit (NICU) of
      Northwest Armed Forces Hospital, Saudi Arabia. Among 75 infants who received
      surfactant for RDS and similar number who were managed during time period just
      before the surfactant was available, but by set criteria would have made them
      eligible for surfactant. All other management modalities except surfactant were
      the same for all these babies. Based on the intensity of monitoring and nursing
      care required by the baby, the level of care was divided as: Level IIIA, IIIB,
      Level II, Level I. The cost per day per bed for each level was calculated, taking
      into account the use of hospital immovable equipment, personal salaries of
      nursing, medical, ancillary staff, overheads and maintenance, depreciation and
      replacement costs. Medications used, procedures done, TPN, oxygen, were all added
      to individual patient's total expenditure. 75 infants in the Surfactant group had
      62 survivors. They spent a total of 4300 days in hospital. (av 69.35) Out of
      which 970 d (av 15.65 per patient) were ventilated days. There were 56 survivors
      in the non-surfactant group of 75. They had spent a total of 5023 days in the
      hospital (av 89.69/patient) out of which 1490 were ventilated days (av 26.60 d).
      Including the cost of surfactant (two doses), cost of hospital stay for each
      infant taking the average figures of stay would be SR 118, 009.75 per surfactant
      treated baby and SR 164, 070.70 per non-surfactant treated baby. The difference
      of 46,061 SR is 39.03% more in non-surfactant group. One Saudi rial = 8 Rs
      (approx at the time study was carried out.) Medical care cost varies from place
      to place. However, it is definitely cost-effective where surfactant is concerned.
      Quality adjusted life years (QALY) for NICU care compares favourably with cost
      per QALY of several forms of adult health interventions. Audit, both medical and
      financial, of these services, at regular intervals is essential.

PMID- 11450379
TI  - Epidemiological study of congenital heart disease.
AB  - A community based survey of congenital heart disease was carried out on a random
      sample of 11,833 children below 15 years in Delhi, India. Congenital heart
      disease was diagnosed on clinical history and/or clinical examination. Out of the
      examined sample, 50 were found suffering from congenital heart disease, giving an
      overall prevalence of 4.2/1000 (4.6/1000 in boys and 3.7/1000 in girls). The
      prevalence rate was slightly higher than other studies carried out in the
      country. The reason is obvious. The present study is community based while other
      studies were hospital or school based. The type of lesions were similar to those
      reported from other studies. The lesions in order of frequency were ventricular
      septal defect (46%), atrial septal defect (18%), patent ductus arteriosus (14%),
      Fallot's tetrology (10%), aortic stenosis (4%), and pulmonary stenosis (4%). Like
      other studies ventricular septal defect was the commonest lesion. The prevalence
      rate was higher in the age group 0-4 years and 5-9 years in boys whereas it was
      higher in adolescent age group (10-14 years) in girls.

PMID- 11450380
TI  - Serum-ascites albumin gradient: a predictor of esophageal varices with ascites.
AB  - Other investigators have found that in adults the Serum-Ascites Albumin Gradient
      (SAAG) to be 1.1 g/dl or greater in the presence of portal hypertension (PTHN)
      and less than that in its absence. We sought to determine the correlation between
      the level of SAAG and the complications of PTHN, manifested by the presence of
      esophageal varices in children with ascites. Our study included 26 patients with
      cirrhosis, diagnosed by liver biopsy and 14 patients with nephrotic syndrome (NS)
      diagnosed by established criteria. The SAAG was measured in all patients. The
      patients with cirrhosis had upper gastrointestinal (GI) endoscopy for assessment
      of esophageal varices (EV). We found that 84.6% (22 of 26) patients with
      cirrhosis had High SAAG (> or = 1.1 g/dl) and 15.4% (4 of 26) had low SAAG (< 1.1
      g/dl) (p < 0.001). EV was found in 91% (20 of 22) patients with high SAAG and in
      50% (2 of 4) patients with low SAAG (p = 0.013). The SAAG differentiated
      cirrhosis with EV from those without EV (sensitivity = 91%, specificity = 50%,
      positive predictive value = 91%, negative predictive value = 50% and efficacy =
      85%). The high SAAG is a useful means to predict the presence of EV in children
      with ascites.

PMID- 11450381
TI  - Brush cytology: an adjunct to diagnostic upper GI endoscopy.
AB  - Endoscopic brush cytology (EBC) was performed in antral and duodenal brushings of
      children subjected to upper GI endoscopy for the detection of H. pylori (Hp) and
      trophozoites of Giardia lamblia (Glt) in addition to routine endoscopic grasp
      biopsy (EGB). It was hospital based prospective study. EBC was performed in
      children subjected to upper GI endoscopy with a sheathed cytology brush. Mucosal
      brushings were collected from antrum, body of the stomach and second or third
      part of duodenum by gently rubbing the surface of the brush with the mucosal wall
      in all the directions, brush withdrawn and brushings performed on a glass slide.
      The smears were placed in 95% ethyl alcohol and later examined for Glt and Hp
      using Giemsa and Hematoxylin & Eosin stain. EGB was taken from antrum, body of
      the stomach and duodenum from sites other than those used for brushings. One
      hundred and seventy children between 1-13 years (median age = 5 years) were
      subjected to upper GI endoscopy for malabsorption (n = 94), recurrent abdominal
      pain (n = 49), failure to thrive (n = 16) and recurrent vomiting/regurgitation (n
      = 11) and EBC was performed in addition to routine EGB. Thirty five children
      (20.4%) were colonized by Hp, 14 (8.2%) were detected to have Glt and in 6 cases
      (3.5%) both Hp as well as Glt were detected. Out of 41 cases colonized by Hp, 24
      cases (58.5%) were detected by EGB and 27 cases (65.8%) were detected by EBC. Out
      of 20 children in whom Glt were detected from their duodenum, the detection was
      by EBG in 12 cases (60%) and by EBC in as many as 19 cases (95%). Comparison of
      EGB and EBC suggested that detection rates with EBC were higher than EGB.
      Detection by EBC was significantly higher for Glt than Hp. There were no
      complications attributed to EBC and procedure time for endoscopy was not
      significantly prolonged. On the contrary, detection of Hp and particularly Glt in
      higher proportion of cases with the help of EBC was helpful in their appropriate
      management. Our results suggest that EBC is a safe and useful tool to enhance the
      value of diagnostic endoscopic procedure when used in combination with routine
      EGB.

PMID- 11450382
TI  - Association between lower hair zinc levels and neural tube defects.
AB  - Though folic acid supplementation has reduced the incidence of Neural Tube
      Defects (NTD), NTD still constitutes one of the important congenital
      malformations having wide medical, social and ethical implications. Zinc
      deficiency has been reported to produce NTD in animals. This study was designed
      to evaluate zinc status of the newborn babies with NTD and their mothers. Eighty
      newborn babies with NTD and their mothers served as cases. Eighty apparently
      normal newborn babies and their mothers served as controls. Serum and scalp hair
      zinc levels were analyzed by atomic absorption spectrophotometry. The mean (+/-
      SD) serum and hair levels in normal mothers were 74.1 +/- 4.1 micrograms/dl and
      142.3 +/- 8.0 micrograms/g respectively. The mean (+/- SD) serum and hair levels
      of the mothers who delivered NTD babies were 75.7 +/- 5.6 micrograms/dl and 129.9
      +/- 5.3 micrograms/g respectively. The mean (+/- SD) serum and hair levels in
      normal newborn babies were 77.8 +/- 5.3 micrograms/dl and 188.8 +/- 6.2
      micrograms/g respectively. The mean (+/- SD) serum and hair levels in NTD babies
      were 80.1 +/- 12.9 micrograms/dl and 174.2 +/- 10.7 micrograms/g respectively.
      The hair zinc levels of the affected babies and their mothers were significantly
      lower (P < 0.001) than the controls. This study has found association between NTD
      and decreased hair zinc levels and large population based studies are recommended
      to confirm the association between zinc and NTD and to investigate whether zinc
      supplementation would reduce the overall incidence of NTD.

PMID- 11450383
TI  - Serum zinc and copper levels in the maternal blood and cord blood of neonates.
AB  - Estimation of serum zinc and copper in the maternal blood and cord blood of
      neonates was carried out to correlate the trace metals in the neonates and their
      mothers in relation to gestational age and birth weight. Sixty-five healthy
      neonates, both term and preterm and their mothers were selected. This cross
      sectional study was done at Azimpur Maternity Centre, Dhaka Medical College
      Hospital and Chemistry Division, Atomic Energy Centre, Dhaka, Bangladesh from
      July 1997 to June 1998. The estimation of trace metals was carried out by Atomic
      Absorption Spectrophotometry (AAS). The mean serum zinc levels in the maternal
      blood and cord blood were 0.47 +/- 0.24 microgram/ml and 0.85 +/- 0.33
      microgram/ml respectively and the mean copper levels in the maternal blood and
      cord blood were 1.37 +/- 0.62 micrograms/ml and 0.31 +/- 0.32 microgram/ml
      respectively. Cord blood zinc level was significantly higher and cord blood
      copper level was significantly lower than the corresponding maternal blood
      levels. There was no significant correlation between gestational age and serum
      zinc levels in the cord or maternal blood. But significant inverse correlation
      was found between gestational age and serum levels of copper in the maternal and
      cord blood.

PMID- 11450384
TI  - Developmental outcomes of newborn encephalopathy in the term infant.
AB  - Newborn encephalopathy is a clinically defined condition of abnormal neurological
      behaviours in the newborn period. Though most cases have their origin in the
      preconceptional and antepartum period, newborn encephalopathy represents a
      crucial link between intrapartum events and permanent neurological problems in
      the child. The birth prevalence of newborn encephalopathy ranges from 1.8 to 7.7
      per 1000 term live births according to the definition used and the population to
      which it is applied. Few studies have investigated the outcomes of newborn
      encephalopathy other than for cases solely attributed to intrapartum hypoxia.
      These adverse outcomes range from death to cerebral palsy, intellectual
      disability, and less severe neurological disabilities such as learning and
      behavioural problems. Outcomes following newborn encephalopathy may vary from
      country to country with 9.1% of affected babies dying in the newborn period in
      Western Australia and 10.1% manifesting cerebral palsy by the age of two. These
      compare to a case fatality of 30.5% in Kathmandu and a cerebral palsy rate of
      14.5% by one year of age. The study by Robertson et al which followed children
      with hypoxic ischaemic encephalopathy found an incidence of impairment of 16%
      among survivors assessed at 8 years with 42% requiring school resource room help
      or special classes. This review emphasises the great need for comprehensive
      clinical and educational assessment as these infants approach school entry to
      enable appropriate educational provisions to be made.

PMID- 11450385
TI  - The child with cerebral palsy--clinical considerations and management.
AB  - Cerebral Palsy (CP) is a non-progressive disorder of the motor system secondary
      to brain injury during early development. Associated non-motor problems are
      frequent and contribute significantly to the disability. While spastic CP is the
      commonest, dyskinetic CP continues to be a problem in our contribute. Acquired CP
      mostly secondary to CNS infections constitutes a significant proportion of cases
      in developing countries. Early diagnosis, proper assessment of the functional
      capacity and needs of the child and providing early intervention are important. A
      multidisciplinary approach to management with active parental involvement helps
      the child achieve his potential.

PMID- 11450386
TI  - Approach to learning disability.
AB  - Learning disabilities (LD) is one of the important causes of poor academic
      performance in school going children. Learning disabilities are developmental
      disorders that usually manifest during the period of normal education. These
      disabilities create a significant gap between the true potential and day to day
      performance of an individual. Dyslexia, dysgraphia and dyscalculia denote the
      problem related to reading, writing and mathematics. Perinatal problems are
      certain neurological conditions, known to be associated with LD; however, genetic
      predisposition seems to be the most probable etiological factors. Evaluation of a
      child suspected to be having LD consists of medical examination, vision and
      hearing test analysis of school performance. The psycho-behaviour assessment and
      education testing are essential in the process of diagnosis. The experienced
      persons in the field of LD should interpret the results of such tests. With
      Individualized Remedial Education Plan (IEP) most children learn to cope up with
      disability and may get integrated in a regular steam.

PMID- 11450387
TI  - Diagnosis and management of children with attention deficit hyperactivity
      disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent
      childhood psychiatric disorder which is characterized by three core symptoms of
      inattention, hyperactivity and impulsivity. It is estimated that 5% to 10% of
      school aged children suffer from this disorder. This disorder is more common in
      boys than girls. Comorbidity is a major problem and is present in as many as two
      thirds of children with ADHD. A multiple modality approach to treatment which
      combines pharmacotherapy, psycho education, behaviour therapy, environmental
      changes and social skills training is recommended. The outcome of ADHD is
      variable and unless properly treated in early years may predispose the child to
      serious psychopathology in adulthood.

PMID- 11450388
TI  - Roberts-SC phocomelia syndrome.
AB  - A severely growth retarded baby was born at 38 weeks gestation. He had multiple
      craniofacial anomalies, microbrachycephaly, phocomelia in the upper limbs and
      renal cysts visible on ultrasound. He died of recurrent apneas. The autopsy
      showed left sided multicystic dysplastic kidney and absence of one testis.
      Cytogenetic studies did not reveal any abnormality. The phenotypic features match
      those described in the Roberts-SC phocomelia syndrome. A literature review
      revealed that 50% of these patients have chromosomal defects and antenatal
      detection is possible on ultrasound and by chromosome analysis of the amniocytes.

PMID- 11450389
TI  - Mixed anaerobic and aerobic testicular abscess in a neonate.
AB  - A premature baby developed a testicular abscess on day 28 of life. The pus
      aspirated from the abscess grew a mixture of beta hemolytic Streptococcus and a
      Bacteroides species. The source of this infection could not be identified. The
      baby improved on antibiotic therapy. This is the first reported case of a
      polymicrobial testicular infection involving an anaerobe in a neonate. The
      relevant literature is reviewed.

PMID- 11450390
TI  - Glanzmann's thrombasthenia.
AB  - Glanzmann's thrombasthenia (GT) is an uncommon cause of bleeding in children. We
      diagnosed two siblings as having GT on the basis of flow cytometric studies. Both
      had cutaneous bleedings and epistaxis since early childhood. Hematological
      investigations revealed prolonged bleeding time and a normal platelet count. Both
      the patients had absence of aggregation of platelets with the agonist adenosine
      diphosphate. Absence of the GPIIb/IIIa receptor was confirmed by flow cytometry.
      A short review of the disorder is presented.

PMID- 11450391
TI  - Landau Kleffner syndrome.
AB  - An eight-year-old male child presenting with history of generalized convulsions,
      gradual loss of speech and generalized EEG (electroencephalography) abnormalities
      was diagnosed as Landau Kleffner Syndrome. He initially developed generalized
      convulsions which later changed to partial seizures during the course of illness.
      He was started on sodium valproate and continued with the drug (30 mg/kg/day) on
      which, he showed improvement in speech, behavior, hyperkinesis and frequency of
      convulsions during the follow-up.

PMID- 11450392
TI  - Strangulation injury, a fatal form of child abuse.
AB  - Strangulation is a common method of committing murder, though underreported in
      Indian literature. We managed a girl child, victim of child abuse who later
      succumbed to its neurological complications. This case report describes the
      clinical features associated with such injuries and complications which should be
      anticipated in such cases.

PMID- 11450393
TI  - Cutaneous anthrax in two siblings.

PMID- 11450394
TI  - [Are androgens responsible for comedone formation?].

PMID- 11450395
TI  - [What to think about bacterial resistances in acne?].

PMID- 11450396
TI  - [What is the role of hormonal treatments in acne?].

PMID- 11450397
TI  - [Acne. Is isotretinoin pro- or anti-inflammatory?].

PMID- 11450399
TI  - [Proceedings of the Interface Committee, INSERM (National Institute of Health and
      Medical Research)-Dermatology. 5 December 2000].

PMID- 11450402
TI  - [Acne. Introduction: which methods for what new treatments?].

PMID- 11450403
TI  - [Acne. The molecular action of androgens].

PMID- 11450404
TI  - [Depression in the elderly].

PMID- 11450405
TI  - [Depression in advanced age: therapeutic aspects].

PMID- 11450406
TI  - [Depression in the elderly. Etiological and clinical aspects].

PMID- 11450407
TI  - [Clinical, biological and social aspects of depression in advanced aged].

PMID- 11450408
TI  - Inadequate implant angulation resulting from oroantral fistula: case report.
AB  - Successful implant surgery is largely dependent on good treatment planning and
      careful surgery. A complete treatment plan must encompass both surgical and
      prosthetic considerations for the implant restoration. Some compromised implants
      are restorable, and the result can be acceptable if they can be adjusted into a
      more ideal position. The goals of the segmental osteotomy are the preservation of
      a healthy dental unit, the creation of a more ideal environment for dental
      restoration and occlusal reconstruction, the optimization of cost effectiveness,
      and the minimization of edentulous space. The purpose of this study is to present
      the segmental maxillary osteotomy to reposition the alveolar segment with its
      implant that was in a highly compromised situation.

PMID- 11450409
TI  - Ridge widening and immediate implant placement: a case report.
AB  - Alveolar atrophy may present an anatomical limitation to the placement of
      endosseous implants. A case is described of severe maxillary alveolar atrophy
      with immediate implant placement associated with a ridge widening technique in
      accordance with a split-crest-bone manipulation. Taper-shaped implants were
      applied in this technique without a barrier membrane. Because this implant was
      small and tapped into position, it was easier to use and was considered to be
      appropriate for the ridge widening technique associated with immediate implant
      placement.

PMID- 11450410
TI  - Provisional implants: surgical and prosthetic aspects.
AB  - Although numerous technological advances have improved the ability of implant
      practitioners to successfully reconstruct dental implants, providing patients
      with teeth during the immediate postsurgical period has remained problematic. One
      solution has been the development of temporary implants. Such provisional
      implants eliminate the need for a tissue-borne prosthesis that may interfere with
      the healing of the submerged conventional implants and/or grafting material. This
      article describes the methodology for placing immediate provisional implants.
      Three alternative approaches to fabrication of the temporary prosthesis are
      discussed, and the results of 12 cases are reviewed.

PMID- 11450411
TI  - Treatment of a microvascular reconstructed mandible using an implant-supported
      fixed partial denture: case report.
AB  - Oral rehabilitation of patients with mandibular discontinuity defects is a
      problem that faces both the oral surgeon and the restorative dentist. Advances in
      microvascular surgery can provide the mandible with vital bone grafts. Often,
      reconstruction of the bony defect alone does not guarantee an adequate foundation
      for successful conventional prosthetic rehabilitation. Osseointegrated implants
      placed in the microvascularized grafted bone offer an opportunity for improved
      function and patient satisfaction. This case report describes the use of an
      implant-supported bridge in a vascularized fibular bone graft to reconstruct a
      traumatic partially resected mandible.

PMID- 11450412
TI  - Experimental study of bone response to a new surface treatment of endosseous
      titanium implants.
AB  - This study examines a new surface treatment that uses coarse calcium phosphate,
      which provides the benefits of surface roughening without introducing any foreign
      materials that may become imbedded in the implants. It is intended to enhance the
      use of implants in areas of inferior bone quality and quantity, such as the
      posterior areas of the maxilla and the mandible. Implants placed in the tibia of
      rabbits were removed after 16 weeks and examined microscopically. Pore sizes
      examined under the scanning electron microscope met the conditions described in
      the literature for successful integration. Optic microscopy revealed evidence of
      bone apposition over the roughened implant surface comparable to that seen in
      other surfaces. There was a definite absence of fibrous tissue, demonstrating
      good-to-excellent bone contact with the Restore Resorbable Blast Media implants
      (Lifecore Biomedical, Chaska, MN). In addition, it appears that the blasting of
      resorbable calcium phosphate on the machine titanium surface results in the
      resorbable blast media surface acting like an inert material. Further studies
      with a larger sample size are needed to confirm these initial findings.

PMID- 11450413
TI  - Bone interface of dental implants cytologically influenced by a modified
      sandblasted surface: a preliminary in vitro study.
AB  - To study the influences of a modified sandblasted surface (developed by the
      authors) on the integrating status of titanium (Ti) dental implants and bone in
      vitro, a three-dimensional experimental model of implant material-osteoblast
      culture was used. The interaction of Ti discs and osteoblasts at the interface
      was followed with phase-contrast microscope examination and was further observed
      histologically and ultra-structurally after one-month culture. Results showed
      that there was no significant difference between the modified sandblasted surface
      group and the smooth surface group in the capacity of osteoblasts migrating and
      attaching to Ti discs. There was, however, a significant difference in the
      pattern of attachment. Around the polished surface, the migrating and attaching
      osteoblasts oriented themselves parallel to it; however, around the modified
      sandblasted surface, the osteoblasts were migrating and attaching
      perpendicularly. There was also a major difference in the shapes of cells lining
      the interface; spindle-shaped on the smooth surface versus round and ovoid with a
      large cellular body and abundant cytoplasm on the modified sandblasted surface.
      Moreover, transmission electron microscopy revealed an active secretion of
      collagen fibrils, a bone-matrix-vesicles-mediated mineralization process, and the
      formation of osteocytes in the modified sandblasted surface group. Therefore, at
      this in vitro level, it can be concluded that the modified sandblasting surface
      treatment of dental implants can facilitate bone healing at their osseous
      interface and enable the real perpendicularly connecting bone-fiber
      osseointegration to form instead of the capsule-like osseous adaptation.

PMID- 11450414
TI  - Comparison of anorganic bovine mineral with and without synthetic peptide in a
      sinus elevation: a case study.
AB  - A new tissue-engineered bone substitute that reportedly has the capability to
      enhance bone regeneration over the more classical bone substitutes, such as
      decalcified freeze-dried bone allograft and xenograft, was evaluated in bilateral
      sinus procedures. Anorganic bone mineral with and without a synthetic peptide (P
      15) were grafted separately in bilateral sinuses. At the time of implant
      placement and at four months, trephine cores were obtained and the quality of the
      grafts deciphered by histomorphometry. The P-15 grafted sinus yielded 45% vital
      bone compared with 13% for the anorganic bovine material alone. The P-15
      dramatically increased the quality and quantity of grafted bone in the sinus.

PMID- 11450415
TI  - Effect of biofluid environment on the dissolution and flexural strength of
      calcium phosphate bone cements.
AB  - This study investigates the dissolution of calcium (Ca2+), phosphorus (P5+), and
      the transverse strength of commercially available calcium phosphate (CaP) bone
      cements after immersion in fetal bovine serum and a tissue fluid substitute. It
      was observed that although a continual increase in Ca2+ and P5+ dissolution was
      detected in all three test media throughout the 21-day period, no statistical
      difference existed in the overall Ca2+ release after incubating the cements in
      the three different media. However, P5+ release after immersion in Tris solution
      (0.37 +/- 0.02 microgram/mm2) and fetal bovine serum solution (0.347 +/- 0.06
      microgram/mm2) was significantly higher when compared with P5+ released (0.03 +/-
      0.002 microgram/mm2) in tissue fluid substitute. In addition, no significant
      difference in transverse strength was observed for samples immersed in the three
      solutions during the 21-day period. However, the transverse strength for immersed
      CaP cement bars at 37 degrees C was statistically greater than non-immersed bars
      set aside at room temperature for the 21-day period (7.78 +/- 1.82 N and 3.19 +/-
      0.93 N, respectively). It was concluded from this study that the transverse
      strength of the CaP bone cements was not significantly affected by the
      dissolution process but by the temperature at which the bone cement was exposed.

PMID- 11450416
TI  - A survey of clinical members of the association of dental implantology in the
      United Kingdom. Part II. The use of augmentation materials in dental implant
      surgery.
AB  - The following were the objectives of Part II of the survey: (1) to determine
      which augmentation materials were used by respondents, (2) to elicit which
      factors influenced the choice of augmentation materials, (3) to establish the
      perceived levels of evidence that support augmentation materials, and (4) to
      ascertain the clinical applications of particulate augmentation materials
      (autografts, allografts, and alloplasts). Autogenous bone and demineralized
      freeze-dried bone are used most frequently. The majority of respondents involved
      in bone augmentation indicated that alloplasts and allografts should be used to
      correct small defects or as volume expanders in conjunction with autogenous bone.
      Research publications and personal clinical observation mainly determine the
      choice of an augmentation material. Of the clinicians who preferred to use
      autogenous bone, 26.3% thought that there was at least one randomized controlled
      trial with histological evidence supporting its use in oral implantology. In
      comparison, 30% of demineralized freeze-dried bone users thought that there was
      at least one randomized controlled trial with histological evidence supporting
      its use. Collected bone debris is currently used for the correction of bone
      dehiscences and fenestrations around endosseous dental implants in the
      simultaneous implant-placement augmentation technique. There is a pressing
      requirement for the two most commonly used augmentation materials (autogenous
      bone and demineralized freeze-dried bone) to be evaluated by accepted scientific
      protocols. Although regard for autogenous bone as an augmentation material is
      high, its use in the form of collected bone debris seems to be limited at
      present.

PMID- 11450417
TI  - Patient screening and medical evaluation for implant and preprosthetic surgery.

PMID- 11450418
TI  - The significance of passive framework fit in implant prosthodontics: current
      status.
AB  - The clinical and laboratory procedures employed for framework fabrication are
      inadequate to provide an absolute passive fit for implant-supported fixed
      superstructures. Although some prosthetic complications are attributed to the
      lack of passive fit, its effect on implant success is questionable. Nevertheless,
      the clinical results of increasing applications of advanced technology to improve
      framework fit seem promising. This article reviews the clinical significance of
      passive fit and the factors that affect the final fit of implant-supported
      frameworks.

PMID- 11450419
TI  - Replacement therapy and the immediate post-extraction dental implant.
AB  - Immediate postextraction implant placement often deals with two major problems:
      maintaining the initial stability of the implant(s) and preventing soft tissue
      ingrowth during the healing period. Both problems may lead to the loss of the
      implant(s). The objective of this clinical study was to evaluate the
      effectiveness, reliability, and placement of single-stage implants in extraction
      sockets in combination with a synthetic bone substitute. Hopeless teeth were
      extracted and one-stage cylindrical screw implants, hollow and solid, were
      inserted together with a composite polymer without using a membrane.
      Rehabilitation was performed three to six months postoperatively by placement of
      different types of prostheses. Excellent initial results were confirmed by the
      follow-up of 7 to 10 years. The hollow screw-type showed a higher failure rate
      when compared with the solid screw-type. One-stage implant osseointegration in
      extraction sockets is enhanced if used with this synthetic graft material, and
      the simplicity of the method does not jeopardize outcome and predictability. It
      provides the patient with the benefits of implant-supported restorations in a
      simple, quick, cost-effective, and secure manner.

PMID- 11450420
TI  - The socioeconomic impact of preterm delivery.

PMID- 11450421
TI  - The comparative physiology of parturition in mammals.

PMID- 11450422
TI  - Relaxin and the cervix.

PMID- 11450423
TI  - Cytokines and the initiation of parturition.

PMID- 11450424
TI  - Prostaglandins, the fetal membranes and the cervix.

PMID- 11450425
TI  - Role of mechanical signals in the onset of term and preterm labor.

PMID- 11450426
TI  - Excitability in uterine smooth muscle.

PMID- 11450427
TI  - Coordination of myometrial contractility.

PMID- 11450428
TI  - The placenta as a neuroendocrine organ.

PMID- 11450429
TI  - Timing the onset of parturition.

PMID- 11450430
TI  - Regulation of CRH gene expression in the placenta.

PMID- 11450431
TI  - Biochemical predictors of prematurity.

PMID- 11450432
TI  - Metalloproteinases and cervical maturation.

PMID- 11450433
TI  - Pharmacotherapy for preterm labour.

PMID- 11450434
TI  - Prostaglandins and uterine activity.

PMID- 11450435
TI  - Oxytocin and uterine activity.

PMID- 11450436
TI  - Control of intracellular signalling by corticotropin-releasing hormone in human
      myometrium.

PMID- 11450437
TI  - Role of the human fetal adrenal gland in the initiation of parturition.

PMID- 11450438
TI  - Roles of estrogen and progesterone in human parturition.

PMID- 11450439
TI  - [Medicinal and chemical approaches to focused search of agents for treatment and
      therapy of Alzheimer disease].
AB  - The analysis and justification of medicinal chemistry approaches for focused
      search of novel agents for Alzheimer's disease (AD) and related disorders
      treatment and prevention have been reviewed. The systematization of modern
      biochemical and structural date related to the action of physiologically active
      compounds on the nervous system apparatus engaged in the AD-like disorders
      pathogenesis was performed. The major attention was paid to the cholinomimetic,
      anti-amyloid and antimetabolic approaches, basing on the results published in
      scientific literature in 3-4 last years and results of preclinical and clinical
      trials, presented in the internet database in the fall of 2000.

PMID- 11450440
TI  - [Changes in physico-chemical properties of biological membranes in development of
      tolerance to ethanol].
AB  - Ethanol can directly influence biological membranes, and increase membrane
      fluidity. This leads to changes in the liquid-crystal state of membranes. These
      changes affect membrane transport, transmembrane signal transduction and activity
      of membrane bound enzymes.

PMID- 11450441
TI  - [Affinity chromatography of nucleoprotein complexes].
AB  - Affinity sorbent containing cellular membranes of the cerebral cortex was
      obtained by means of an inclusion into porous matrix of polyacrylonitrile.
      Sorption of model and natural nucleoprotein complexes on the obtained sorbent was
      studied by the method of affinity chromatography. Distribution coefficients were
      determined. Natural nucleoprotein complexes isolated from brain possess a greater
      selectivity of binding to the cellular membranes of the cerebral cortex than that
      from liver.

PMID- 11450442
TI  - [Liver mitochondria in antigenic stress in rats].
AB  - The penomenon of reciprocal regulation of succinate dehidrogenase activity in rat
      liver mitochondria was elicited in antigenic strain induced by the administration
      of activated lymphocytes from animals with allotransplated heart. Two coupled but
      opposite changes (simultaneous activation and inhibition) in succinate depended
      ATP synthesis and calcium transport occur. The inhibition was correlated with the
      activation of synthetic processes in hepatocytes. Similar changes were provoked
      by epinephrine (either administered i.p. or released endogenously under
      immobilization stress and in myocardium infarction) as well as in patients with
      stomach tumor. The physiological significance of the reciprocal regulation of
      succinate dehydrogenase is discussed.

PMID- 11450443
TI  - [Peptide analog of apolipoprotein E increases clearance of lipoproteins and
      decreases level of serum cholesterol].
AB  - Apolipoprotein E mediates lipoprotein binding to the low density lipoprotein
      (LDL) receptor and to the LDL receptor-related protein. Apolipoprotein E 139-158
      peptide increases micellar binding and endocytosis by hepatocytes. The
      lipophilicity of the peptide was increased by modification of its N-terminus by
      acylation with palmitic acid ether. The peptide mediates acute clearance of the
      lipoproteins and decreases the cholesterol level in rat blood. Total cholesterol
      level, high density lipoprotein cholesterol and apolipoprotein B were measured in
      the serum after intravenous administration of the acylated peptide.

PMID- 11450444
TI  - [Effects of bile acid preparations on DNA biosynthesis, apoptosis, and necrosis
      in hepatocytes in vitro].
AB  - Using primary culture of hepatocytes it was shown that glycochenodeoxycholic acid
      (GCDCA) in a dose dependent manner induces apoptosis or necrosis of the
      hepatocytes and inhibits DNA biosynthesis. Ursodeoxycholic acid (UDCA) and
      tauroursodexycholic acid (TUDCA) do not cause apoptosis or necrosis of the
      hepatocytes in a range of doses 25-400 micrograms/ml. But in the presence of
      GCDCA both preparations have an antiapoptosogenic effect and TUDCA has also an
      antinecrosogenic effect.

PMID- 11450445
TI  - [Changes in the activity of enzymes of heme synthesis and catabolism, and level
      of microsomal hemoproteins during the liver acute intoxication by thioacetamide].
AB  - Thioacetamide administration to rats (20 mg/100 g) caused the development of
      toxic hepatitis which was accompanied by the increase of hepatic ALA-synthase and
      D-ALA that led to accumulating free porphyrines in the liver. At the same time an
      increase in activity of heme oxigenase was also found. A decrease in heme
      synthesis correlated with a decrease in content of cytochrome P450 and b5 in
      microsomal hepatic fraction of experimental animals.

PMID- 11450446
TI  - [The role of single amino acid residues of the immunodominant continuous epitope
      of cytochrome P450CAM (CYP101) 312LKKGDQ317 in recognition by specific
      antibodies].
AB  - As it has been shown previously the site 311-318 of bacterial cytochrome P450cam
      (CYP101) contains an immunodominant continuous B-epitope. In order to investigate
      the role of single amino acid residues in antibody binding antigenic hexapeptide
      312LKKGDQ317 analogues including single amino acid replacements were synthesized
      using Multipin technology. Antibodies from three anti-P450cam polyclonal rabbit
      sera interacted similarly to these peptides. The residue G315 was found to play a
      significant role in antibody recognition; any replacement leads there to
      considerable decrease of antibody binding. Residues L312, K313 and D316 occurred
      to be partly replaceable, whereas K314 and Q317 were not essential in
      recognition. These results correspond to known spatial structure of P450cam
      molecule. In its 312-317 site the polypeptide chain makes a turn and so some
      water-accessible atoms form a compact surface cluster including side chain atoms
      of K313 and D316, O-atom of K314 and C alpha-atom of G315, which present reliable
      Ig binding site. Side chain of K314 outlying from this cluster does not
      participate in the interaction. The received data permit to consider that the
      continuous epitope 312-317 of P450cam is conformationally dependent.

PMID- 11450447
TI  - [Effect of antibiotic therapy on embryotropic antibody level in women].
AB  - Embriotropic antibodies (e-Ab) serum contents were analysed in 29 serum samples
      obtained from women suffering with primary lues. Before treatment the content of
      e-Ab against MBP, S100, ACBP14/18, and MP65 were markedly elevated in 28 samples.
      Two injections of Retarpen (2.5 mln Units with one week interval) were enough for
      effective treatment of lues. At the same time treatment caused deep and
      reversible inhibition of e-Ab production. One or two months later the levels of e
      Ab returned to normal values in 21% of women, in 52% patients the hypoproduction,
      and in 27% the hyperproduction of e-Ab were noted. Deviations of e-Ab production
      after effective retarpen treatment suggest the existence of additional reasons
      which may influence e-Ab production, and necessity of additional diagnostic and
      curative measures for such women during pregravidal period.

PMID- 11450448
TI  - [Effect of gamma-plant preparation on production of TNF-alpha, IL-1 beta, and IL
      6 in human peripheral blood mononuclear cells in vitro].
AB  - The effect of a new medicine gamma-plant has antiinflammatory activity on human
      peripheral blood mononuclear cells obtained from healthy donors was studied. Its
      ability to influence TNF, IL-1 and IL-6 production via mononuclear cells was
      determined. Lymphokines spontaneous production and lymphokines productions by
      cells stimulated by LPS was studied. IL-1 content was defined with IL-1 sensitive
      cell line D10G4.1 while IL-6 content with IL-6 dependent heterohybridoma D6C8.
      TNF activity in supernatants was determined as lysis grade of TNF-sensitive cells
      of mouse fibrosarcoma L-929. It was shown that gamma-plant acted as stimulator
      when IL-1 production was low and as inhibitor when it was high. Stimulation of IL
      6 production induced with LPS was achieved by low gamma-plant doses while for
      stimulation of spontaneous production higher doses were required. After
      nonstimulated LPS peripheral blood cells were treated with gamma-plant
      statistically sensible stimulated TNF production was observed apart from TNF
      synthesis level in a control group. The TNF production inhibition could never be
      demonstrated in subjects that showed in control cultures stimulated with LPS a
      level of TNF production lower than 100 pg/ml. In four of the five high TNF
      producers the cytokine release inhibition in LPS stimulated cultures has been
      observed. It is likely that the mild stimulation of the proinflammatory cytokine
      system has taken place. For example, simultaneously with stimulation of cytokine
      production the circulating IL-1 receptor antagonist and/or soluble TNF receptor
      may be induced.

PMID- 11450449
TI  - [Growth and carbohydrate metabolism of sulfobacilli].
AB  - The moderately thermophilic acidophilic bacteria Sulfobacillus
      thermosulfidooxidans, strain 1269, S. thermosulfidooxidans subsp. "asporogenes,"
      strain 41, and the thermotolerant strain S. thermosulfidooxidans subsp.
      "thermotolerans" K1 prefer mixotrophic growth conditions (the concomitant
      presence of ferrous iron, thiosulfate, and organic compounds in the medium). In
      heterotrophic and autotrophic growth conditions, these sulfobacilli can grow over
      only a few culture transfers. In cell-free extracts of these sulfobacilli, key
      enzymes of the Embden-Meyerhof-Parnas, pentose-phosphate, and Entner-Doudoroff
      pathways were found. The role of a particular pathway depended on the cultivation
      conditions. All of the enzymes assayed were most active under mixotrophic
      conditions in the presence of Fe2+ and glucose, suggesting the operation of all
      of the three major pathways of carbohydrate metabolism under these conditions.
      However, the operation of the Entner-Doudoroff pathway in strain 41 was
      restricted under mixotrophic conditions. After the first culture transfer from
      mixotrophic to heterotrophic conditions, the utilization of glucose occurred only
      via the Embden-Meyerhof-Parnas and Entner-Doudoroff pathways. After the first
      culture transfer from mixotrophic to autotrophic conditions, the activity of
      carbohydrate metabolism enzymes decreased in all of the strains studied; in
      strain K1, only the glycolytic pathway remained operative. The high activity of
      fructose-bisphosphate aldolase, remaining in strain 41 cells under these
      conditions, suggests the involvement of this enzyme in the reactions of the
      Calvin cycle or of gluconeogenesis.

PMID- 11450450
TI  - [Effect of sodium azide on heat-shock resistance in Saccharomyces cerevisiae and
      Debaryomyces vanriji yeasts].
AB  - The pretreatment of Saccharomyces cerevisiae and Debaryomyces vanriji with sodium
      azide was found to induce thermotolerance in both yeasts, whereas sodium azide
      used in combination with heat shock enhanced the thermotolerance of S. cerevisiae
      and substantially decreased the thermotolerance of D. vanriji. It is suggested
      that the different responses of the yeasts to sodium azide during heat shock are
      due to the different functional organizations of their mitochondrial apparatus.

PMID- 11450451
TI  - [Lipids from the green algae Botryococcus during staged growth in batch mode].
AB  - The lipid fraction of the green alga Botryococcus cultured in a batch mode was
      found to contain polar lipids (more than 50% of the total lipids), di- and
      triacylglycerides, steroids and their esters, free fatty acids, and hydrocarbons.
      In senescent culture, the content of polar lipids somewhat decreased and that of
      triacylglycerides increased by more than four times. The content of hydrocarbons
      in the algal biomass did not exceed 0.9% and depended little on the culture age.
      Intracellular lipids contained saturated and unsaturated (mono-, di-, and
      trienoic) fatty acids. The maximum content of C16:3 and alpha-C18:3 fatty acids
      (up to 35% of the total fatty acids) was detected in the phase of active growth.
      The extracellular and intracellular lipids of the alga differed in the proportion
      of particular lipids and in the fatty acid pattern.

PMID- 11450452
TI  - [Effect of butyric acid on physiologic activity of carbohydrate-oxidizing
      rhodococci].
AB  - Laboratory experiments showed that butyric acid not only fails to meet the
      trophic requirements of hydrocarbon-oxidizing microorganisms, but even
      specifically inhibits their assimilatory and dissimilatory activity. Therefore,
      butyric acid can be referred to as growth inhibitors. The combined mineralization
      of carbohydrates and hydrocarbons can be described as follows. Plants polymers
      are converted to monosugars by heterotrophic soil microorganisms. As the
      concentration of the monosugars grows and oxygen becomes deficient, the
      monosugars are no longer oxidized completely but are fermented. As a result,
      glucose transforms to butyric acid, which inhibits hydrocarbon-oxidizing
      bacteria. It is concluded that, to be efficient, the cleanup of oil-contaminated
      soils must include measures to intensify the mineralization of carbohydrates and
      to inhibit their fermentation.

PMID- 11450453
TI  - [Degradation of machine oil by nocardiform bacteria].
AB  - Gas liquid chromatography (GLC) was used for the first time to screen for machine
      oil-degrading microorganisms. Oil degradation was evaluated from the
      microorganism respiratory activity during the utilization of oil as the sole
      carbon and energy source. The results are consistent with those obtained by the
      conventional weighing method. Substrate specificity of the active strains with
      respect to different machine oils was studied. Bacterial communities exhibited
      the highest activity, whereas a Rhodococcus erythropolis strain was the most
      active among pure cultures. Various stages of bacterial interaction with oil
      drops were followed by means of fluorescent microscopy.

PMID- 11450454
TI  - [Microbial decomposition of 3,4-dichloroaniline, adsorbed by activated charcoal].
AB  - The accessibility of 3,4-dichloroaniline (DCA) sorbed by activated carbon to
      degradative microorganisms was studied. A Paracoccus denitrificans strain capable
      of growing on medium with DCA as the only source of energy, carbon, and nitrogen
      was used in the experiment. The high sorption capacity of all the carbons studied
      (powdered RS and SKT-6A and granular AG-3) in relation to DCA (350 to 360, 480 to
      520, and 540 to 580 mg/g, respectively) was demonstrated. The sorption capacity
      correlated positively with the specific surface area and the total volume of the
      sorbent micropores. The bulk of the DCA was reversibly sorbed and amenable to
      microbial decomposition; however, the decomposition rates significantly differed.
      When RS, SKT, and Agrosorb preliminarily saturated with DCA were incubated in a
      culture of P. denitrificans, the bulk of the reversibly sorbed DCA was decomposed
      (in the absence of the other carbon sources) in 2, 5, and 10 weeks, respectively,
      after which the process slowed down. At the end of the experiment (29 weeks), 81
      to 87% of the DCA underwent full mineralization, which was accompanied by the
      release of chlorine ions; a small fraction of the xenobiotic (0.8 to 1.9%)
      remained a reversibly sorbed fraction (extractable with acetone), and 12 to 17%
      of the initial DCA seemed to have been chemically transformed and bound by
      carbon. The studied carbons may be used in biological decontamination of
      chloroaniline-polluted soils to decrease the toxic effect of chloroanilines on
      microorganisms.

PMID- 11450455
TI  - [Ultrastructure of the cell surface of heteromorphic Nostoc muscorum CALU 304
      cocultured with Rauwolfia tissue].
AB  - The ultrastructure of the heteromorphic cells (HMCs) of the cyanobacterium Nostoc
      muscorum CALU 304 grown in pure culture, monoculture, and a mixed culture with
      the Rauwolfia callus tissue was studied. The comparative analysis of the cell
      surface of HMCs, the frequency of the generation of cell forms with defective
      cell walls (DCWFs), including protoplasts and spheroplasts, and the peculiarities
      of the cell surface ultrastructure under different growth conditions showed that,
      in the early terms of mixed incubation, the callus tissue acts to preserve the
      existing cyanobacterial DCWFs, but begins to promote their formation in the later
      incubation terms. DCWFs exhibited an integrity of their protoplasm and were
      metabolically active. It is suggested that structural alterations in the rigid
      layer of the cell wall may be due to the activation of the murolytic enzymes of
      cyanobacteria and the profound rearrangement of their peptidoglycan metabolism
      caused by the Rauwolfia metabolites diffused through the medium. These
      metabolites may also interfere with the functioning of the universal cell
      division protein of bacteria, FtsZ. In general, the Rauwolfia callus tissue
      promoted the unbalanced growth of the cyanobacterium N. muscorum CALU 304 and
      favored its viability in the mixed culture. The long-term incubation of the
      Rauwolfia tissue with the N. muscorum CALU 304 cells led to their transformation
      to L-forms.

PMID- 11450456
TI  - [Effect of Rhizobium leguminosarum 252 agglutinins on the activity of some plant
      cell enzymes].
AB  - The incubation of pea seedling roots with the surface agglutinins R1 and R2 of
      Rhizobium leguminosarum 252 brought about an increase in the activity of
      proteases, beta-glucosidase, and, especially, succinate dehydrogenase in the
      roots. The data presented show that rhizobial agglutinins play an important part
      in the formation and functioning of legume-rhizobial associations.

PMID- 11450457
TI  - [Characteristics of infection of plants and their cultured tissue with
      cyanobacterial-bacterial symbiotic associations].
AB  - The infection of tobacco, nightshade, rice plants, and their tissue cultures with
      the cyanobacteria-bacteria symbiotic associations (CBSA) isolated from natural
      syncyanoses (the ferns Azolla pinnata and Azolla sp. and the cycad Encephalartos
      ferox) was studied. The inoculation of the intact plants or their cuttings with
      CBSA led to the colonization of the plant roots, stems, and leaves by
      cyanobacteria and their bacterial symbionts (referred to as satellite bacteria,
      SB). The sites of the long-term contact of plant organs with cyanobacteria were
      characterized by the formation of copious slime. On the roots of infected plants,
      one could observe the callus growth of cortical parenchyma cells and the
      formation of pseudonodules, in which SB cells gradually accumulated. In mixed
      cultures of plant callus tissues and the CBSA isolated from the ferns A. pinnata
      and Azolla sp., the callus tissue specifically influenced the growth of the CBSA
      components, causing (depending on the plant species and strain) either their
      balanced growth, or their cyclic growth, or the predominant growth of one of the
      CBSA components (either cyanobacteria or satellite bacteria). This phenomenon is
      proposed to be used for the dissociation of stable multicomponent natural
      symbiotic complexes and the selection of their particular components.

PMID- 11450458
TI  - [Use of polymerase chain reaction for searching for producers of ergot alkaloids
      from among microscopic fungi].
AB  - The potential of the polymerase chain reaction for the detection of ergot
      alkaloid producers among microscopic fungi of the genera Penicillium and
      Claviceps was evaluated. Twenty-three strains of various species of fungi with a
      previously studied capacity for alkaloid production were used. The internal
      fragment of the gene encoding 4-dimethylallyltryptophan synthase, the enzyme
      catalyzing the first step in the biosynthesis of ergot alkaloids, was amplified
      using degenerated primers. This approach revealed an about 1.2-kb specific DNA
      fragment in micromycetes synthesizing ergot alkaloids with complete tetracyclic
      ergoline system. Microorganisms that produce alkaloids with modified C or D
      ergoline rings, as well as alpha-cyclopiazonic acid, did not yield the PCR
      fragment of the expected size. This fragment was also not found in fungi
      incapable of ergot alkaloid production.

PMID- 11450459
TI  - [Williopsis saturnus and Williopsis beijerinckii-different taxons from polymerase
      chain reaction data with nonspecific primers].
AB  - Fifteen strains of the yeast Williopsis sensu stricto were analyzed by means of
      UP-PCR. With the N21 universal primer, this approach showed that the strains
      could be clearly divided into two groups corresponding to the species W. saturnus
      (Klocker) Zender and W. beijerinckii (van der Walt) Naumov et Vustin. The results
      obtained are in good agreement with data of genetic and isoenzyme analyses and
      provide no support for the conspecificity of W. saturnus and W. beijerinckii
      commonly accepted in modern determination manuals.

PMID- 11450460
TI  - [Bacterial microflora on disinfected sugar beets].
AB  - Sugar beet seeds disinfected with the carbofuran-containing insecticide adifur
      and the fungicide tachygaren by seed-producing firms were found to be abundantly
      populated with bacterial microflora. The bacteria isolated from the seed surface
      were identified to a species level. The selection of bacteria with respect to
      pesticide resistance may lead to the obtaining of agronomically useful bacterial
      strains.

PMID- 11450461
TI  - [Features of microorganism distribution in the Al-Fe-humus podzol of the northern
      taiga spruce forests: natural and technogenic aspects].
AB  - Natural and anthropogenically induced seasonal variations in the abundance and
      biomass of various groups of microorganisms in the Al-Fe-humus podzols of boreal
      spruce forests were analyzed. The fungal biomass in these soils was found to be
      considerably higher than the bacterial biomass. Microbial population was mainly
      concentrated in a thin surface layer (10-15 cm in thickness), which included the
      forest litter and the upper mineral root-inhabited soil horizon and greatly
      differed from other soil horizons in morphology and other properties. This layer
      was found to be optimal with respect to hydrothermal and nutritional conditions
      and was characterized by profound seasonal variations in the abundance and
      biomass of microbiota. The high acidity, typical of the Al-Fe-humus podzols,
      resulted from the metabolism of their microbial communities. In the polluted
      podzols, the population of prokaryotes increased and that of eukaryotes
      decreased.

PMID- 11450462
TI  - [Participation of azospirillium polysaccharides in interaction with wheat root
      surface].
AB  - The present study was undertaken to comparatively investigate the attachment
      capacities of Azospirillum brasilense Sp245 and its lipopolysaccharide-defective
      Omegon-Km mutants KM018 and KM252, as well as their activities with respect to
      the alteration of the morphology of wheat seedling root hairs. The adsorption
      dynamics of the parent Sp245 and mutant KM252 strains of azospirilla on the
      seedling roots of the soft spring wheat cv. Saratovskaya 29 were similar;
      however, the attachment capacity of the mutant KM252 was lower than that of the
      parent strain throughout the incubation period (15 min to 48 h). The mutation led
      to a considerable decrease in the hydrophobicity of the Azospirillum cell
      surface. The lipopolysaccharides extracted from the outer membrane of A.
      brasilense Sp245 and mutant cells with hot phenol and purified by chromatographic
      methods were found to induce the deformation of the wheat seedling root hairs,
      the lipopolysaccharide of the parent strain being the most active in this
      respect. The role of the carbohydrate moiety of lipopolysaccharides in the
      interaction of Azospirillum cells with plants is discussed.

PMID- 11450463
TI  - [Ecophysiological features of mat-forming bacteria Thioploca in bottom sediments
      of Frolikha Bay, northern Baikal].
AB  - A colorless sulfur bacterium of the genus Thioploca, which forms bacterial mats,
      was studied in the region of underwater thermal vents (Frolikha Bay, northern
      Baikal). The organism occurs under microaerobic conditions in top sediment
      layers, and its biomass can amount to 65 mg of wet weight per 1 kg of silt.
      Individual filaments of the bacterium penetrate the anaerobic zone to the depth
      of 19 cm. Thioploca is distributed in a mosaic pattern over the bottom of the
      bay. Thioploca mats are typically found near vents that discharge low-temperature
      underground water. In the form of separate filaments, this bacterium is more
      widely distributed in the top sediment layer, particularly in sediments with a
      more active sulfate reduction. The bacteria from the deep-water and coastal areas
      of the bay have different morphology. Cells of Thioploca are able to accumulate
      nitrate, and the coefficient of nitrate accumulation in wet bacterial mass in
      relation to the near-bottom water is 1.3 x 10(4), suggesting a similarity of
      metabolism with seawater species. A more lightweight isotopic composition of
      nitrogen in cell mass as compared to that of representatives of zoobenthos also
      indicates an active metabolism of nitrogen, apparently, in the process of
      nitrogen respiration. Comparison of the composition of stable isotopes of carbon
      in the biomass of representatives of different trophic levels, including
      Thioploca, found at a depth of 105 m indicates its planktonic origin, whereas, in
      the deeper bay region, the biomass of Thioploca incorporates more of the light
      carbon originating from biogenic methane.

PMID- 11450464
TI  - [New aerobic methyltrophic isolates from the Soda lakes of the southern
      Transbaikal].
AB  - Twenty-one bacterial associations isolated from the soda lakes of the southern
      Transbaikal region were found to be able to actively grow at pH 9-10 on methanol
      as the source of carbon and energy. Two alkalitolerant facultatively
      methylotrophic strains, Bur 3 and Bur 5, were obtained in pure cultures. Both
      strains represent gram-negative, nonmotile, bean-shaped, encapsulated cells that
      reproduce by binary fission. The strains are able to grow at temperatures ranging
      from 6 to 42 degrees C, with an optimum growth temperature of 25-29 degrees C
      (strain Bur 3) and 35-37 degrees C (strain Bur 5) and at pH between 6.5 and 9.5,
      with an optimum pH value of 8.0-8.5. At pH 9.0, strain Bur 3 exhibits an
      increased content of phosphatidylglycerol and a decreased content of
      phosphatidylethanolamine. Strains Bur 3 and Bur 5 are similar in the G + C
      content of their DNAs (66.2 and 65.5 mol %, respectively) and in the type of the
      dominant ubiquinone (Q10). Unlike Bur 5, strain Bur 3 is able to grow
      autotrophically in an atmosphere of CO2 + O2 + H2. The strains oxidize, by the
      respective dehydrogenases, methanol to CO2, which is assimilated via the ribulose
      bisphosphate pathway. Ammonium ions are assimilated in the glutamate cycle and by
      the reductive amination of alpha-ketoglutarate. The strains are highly homologous
      to each other (92%) and are much less homologous (at a level of 28-35%) to
      representatives of the genus Ancylobacter, A. aquaticus ATCC 25396T and A.
      vacuolatum DSM 1277. Based on the results obtained, both strains are assigned to
      a new species, Ancylobacter natronum sp. nov.

PMID- 11450465
TI  - [Effect or preliminary filtration on the functional characteristics of
      bacterioplankton from Lake Khanka].
AB  - The dependence of the functional characteristics of bacterioplankton from the
      loess of Lake Khanka on the pore size of filtering materials was investigated.
      Soluble organic matter (SOM), bacteria, and bacterial consumers adsorbed on
      particles suspended in the lake water were found to filter differently depending
      on the pore size of the filtering material. Filters with pore size 4.5 microns
      (filters II) retained up to 20% of SOM and 20-30% of bacterial cells. Filters III
      with pore size 2.87 microns retained almost 50% SOM and about 40% of bacteria.
      The double layer of gauze no. 72 (referred to as filter I) with pores size 40
      microns was unable to completely retain bacterial consumers. In the case of
      filtrates I and II, the generation time of bacterioplankton decreased with its
      increasing average daily concentration. In the case of filtrate III, the
      generation time of bacterioplankton was minimum and did not depend on its
      concentration. Oxygen consumption rates per one bacterial cell and per unit
      biomass in filtrates increased with decreasing pore size of the filters through
      which they had passed. The bacterial biomass and oxygen consumption rate
      increased exponentially in filtrates III and logarithmically in filtrates I.

PMID- 11450466
TI  - [Micromycetes and actinobacteria under conditions of many years of natural
      cryopreservation].
AB  - Almost all of the investigated samples of the Arctic and Antarctic permafrost
      sediments of different genesis with ages from 5-10 thousand to 2-3 million years
      were found to contain viable micromycete and bacterial cells. The maximum amounts
      of viable cells of fungi (up to 10(4) CFU/g air-dried sample) and bacteria (up to
      10(7)-10(9) CFU/g air-dried sample) were present in fine peaty sediment samples
      taken from different depths. The identified micromycetes belonged to more than 20
      genera of the divisions Basidiomycota, Ascomycota, and Zygomycota, and some
      represented mitosporic fungi. Thawing the samples at 35 and 52 degrees C allowed
      the number of detected fungal genera to be increased by more than 30%. Aerobic
      heterotrophic prokaryotes were dominated by coryneform, nocardioform, and spore
      forming microorganisms of the order Actinomycetales. Analysis of the isolated
      fungi and actinomycetes showed that most of them originated from the microbial
      communities of ancient terrestrial biocenoses.

PMID- 11450467
TI  - [Analysis of the interaction between size of cells and level of antilysozyme
      activity in Escherichia coli batch cultures].

PMID- 11450468
TI  - [Transformation of 3,4-dichloroaniline under nitrate-reducing conditions].

PMID- 11450469
TI  - [Zonal distribution of epiphytic microorganisms on the sea grass Zostera marina].

PMID- 11450470
TI  - [Spatial distribution of bacteria from various physiologic groups near a
      underwater thermal source in Frolikha bay, northern Baikal].

PMID- 11450471
TI  - [Prevention of age-related macular degeneration?].

PMID- 11450472
TI  - [Macular pigment and age-related macular degeneration].
AB  - The present concepts of the pathogenesis of AMD include cumulative light damage
      by oxidative processes in the macular photoreceptors as environmental co-factor
      for the development of AMD. The direct causative connection of this hypothesis
      has still to be established but wide circumstantial evidence from epidemiological
      and basic scientific investigations are strongly supportive. Macular pigment
      consisting of lutein and zeaxanthin through there ability to filter light and by
      direct antioxidative properties, has been proposed as the most effective
      protective factor in the central retina ("natural sun glasses") and could be
      important to reduce light induced oxidative retinal damage. The observation, that
      with age and especially in eyes with AMD lower concentrations of macular pigment
      could be found, can be interpreted that low macular pigment concentrations may be
      associated with higher risk for AMD. Through dietary intake and eventually with
      supplementation the concentration of macular pigment can be increased, and
      analysis of the correlation between macular pigment and AMD may be important to
      characterise a possible influenceable AMD risk factor.

PMID- 11450473
TI  - [Vitamin A metabolism and retinal degeneration].
AB  - Vitamin A plays an important role in the pathogenesis and during the course of
      retinal degenerations. Following a brief overview of the metabolic pathway of
      Vitamin A from the entrance into the body to the arrival in retinal target
      structures, the most important retinal degenerations that are related to the
      Vitamin A-metabolism are presented. Ways of prevention or therapy of such
      diseases are discussed in the light of the still incomplete knowledge about basic
      mechanisms of retinol transport and metabolism.

PMID- 11450474
TI  - [Administration of vitamin A derivatives in hereditary retinal degeneration.
      Status of recommendations].

PMID- 11450475
TI  - [Thrombophilia factors as inducers of retinal vascular occlusion].
AB  - PURPOSE: Thrombophilic abnormalities and defects in the anticoagulant system,
      such as protein C or protein S deficiency, activated protein C resistance and
      factor V Leiden mutation, may produce retinal vascular occlusions. PATIENTS:
      Blood samples from 66 consecutive retinal vascular occlusion patients were
      obtained and analysed for protein C resistance and fibrinolysis activity. Other
      thrombophilic and standard laboratory coagulant tests were also carried out.
      RESULTS: An increased activity of factor VIII was found in 72% of the collective.
      Furthermore, 24% of all patients and 32% of patients younger than 45 years old
      were resistant to activated protein C. Nevertheless only one patient showed a
      homozygous factor V Leiden mutation. CONCLUSION: Thrombophilic activity in cases
      of protein C resistance or factor V Leiden mutation may result in severe
      thrombotic manifestations in ocular vessels. Compared to the elderly, younger
      people showed a higher activated protein C resistance which seems be one of the
      most common causes for retinal vascular occlusion in this age group.

PMID- 11450476
TI  - [Effect of latanoprost on ocular hemodynamics and contrast sensitivity].
AB  - BACKGROUND: Latanoprost effectively lowers intraocular pressure. Because ischemia
      has gained increasing importance in the pathogenesis of glaucoma, an
      antiglaucomatous drug should also be investigated with regard to the influence on
      ocular hemodynamics. METHODS: In a double masked, randomized, clinical trial,
      Latanoprost eye drops were administered to 15 volunteers once daily for 8 days
      and 15 further volunteers received placebo eye drops according to the same
      protocol. IOP, blood pressure, heart rate, ocular pulse amplitudes, pulse volume,
      pulsatile ocular blood flow and contrast sensitivity were measured before (1T0),
      120 min after drop administration (1T120), after 7 days of therapy (8T0) and
      again 120 min after an acute administration (8T120). For statistical analysis a
      two-way variance-analysis and the t-test for paired samples were used. RESULTS:
      IOP was found to be statistically significantly different comparing both groups
      over the test period (p = 0.036). In Latanoprost-treated subjects the t-test
      revealed a significant drop in IOP between 1T0 and 8T0 (p = 0.009) and between
      1T0 and 8T120 (p < 0.0001). All other above mentioned parameters remained
      constant. CONCLUSION: In Latanoprost-treated subjects, a significant drop in
      intraocular pressure was observed after 1 week. However, ocular perfusion and
      contrast sensitivity did not change during therapy. This might be due to an
      effective autoregulation in healthy volunteers.

PMID- 11450477
TI  - [Capsular rupture in cataract operations with sponge surface and intra-anterior
      chamber anesthesia].
AB  - BACKGROUND: Combined topical and intracameral anaesthesia has become increasingly
      popular in cataract surgery. The purpose of this study was to determine the risk
      of capsular lesions with an intact motility during surgery. PATIENTS AND METHODS:
      In a prospective clinical study, we analyzed 2000 phacoemulsifications with IOL
      implantation performed by an experienced surgeon with combined sponge and
      intracameral lidocain anaesthesia. Preoperatively two grades of difficulty of the
      surgical procedure were defined. RESULTS: Operations were carried out on 1,658
      patients with a (grade 1) low degree and 342 patients (grade 2) with a high
      degree of difficulty (17.1%). Capsular lesions occurred in 17 operations (0.85%),
      15 in cases with a high degree of difficulty (88%). In 12 of these, an anterior
      vitrectomy was necessary and in 1 operation a pars plana vitrectomy after
      application of additional retrobulbar anaesthesia was performed. CONCLUSIONS: In
      this study the incidence of capsular lesions was not increased compared to other
      methods of anaesthesia. Anterior vitrectomy with the patient under combined
      sponge and intracameral anaesthesia, was possible without retrobulbar
      anaesthesia.

PMID- 11450478
TI  - [Cornea donation. Factors influencing consent].
AB  - BACKGROUND: The purpose of the study was to determine factors that influence the
      decision of the next living relative of a deceased for consent on cornea
      donation. METHODS: The interviews with the relatives of 94 potential cornea
      donors of the Eye Bank of the Ludwig-Maximilians-Universitat, Munich were
      analysed. The influence of sociological factors on the frequency of obtained
      consent was investigated. RESULTS: During a 3-month-period, 77 relatives of 94
      possible donors were asked for consent to cornea donation and 56 consents (73%)
      and 21 refusals (27%) were obtained. In 17 (18%) of the cases the relatives could
      not be reached. Analysis showed a higher consent rate for donors with a
      university degree (82%) versus those without (71%). Consent was more often
      obtained for donors who were divorced (88%) than from those who were single
      (62%). Children of full age (83%) consented more frequently to cornea donation
      than husbands and wives (78%) or the parents of the deceased (60%). Examination
      of the postal codes of the residential area indicated more frequent refusals for
      donors from the rural (54% consent rate) than the urban Munich population (77%
      consent rate). The situation was the opposite for the residential area of the
      consenting relative where there was a higher willingness to donate in cases of
      suicide (93%) in contrast to other causes such as natural deaths (78%) and
      traffic accidents (71%). CONCLUSION: Socio-economic factors such as education,
      marital status, residential area and situational factors such as the cause of
      death, play an important role on the willingness to consent to donate. This study
      can improve the understanding of the donor family's decision making and as such
      help the physician asking for consent and improve information to the public which
      may increase the number of cornea donors in Germany.

PMID- 11450479
TI  - [Follow-up of endothelial cell density after perforating keratoplasty. Effect of
      donor and recipient-related factors].
AB  - PURPOSE: Endothelial cell loss can be observed after keratoplasty, therefore in a
      retrospective study we analysed whether there is a correlation between donor age,
      recipient age, time post-mortem, preoperative cell density, diagnosis of the
      recipient and postoperative endothelial cell density. METHODS: The endothelial
      cell densities of 120 patients who had undergone penetrating keratoplasty were
      examined over a period of 2 years. We divided the patients into four groups based
      on the endothelial cell density over 2 years. We examined the groups with regard
      to the parameters given above. RESULTS: The lowest postoperative cell densities 2
      years after keratoplasty showed a high correlation with the highest donor and
      recipient age. Even the lowest preoperative cell density was found in this group.
      Patients who underwent keratoplasty because of keratoconus had the highest cell
      densities after 2 years and also the lowest donor and recipient age. The
      preoperative cell density was also highest in this group. DISCUSSION: The results
      indicate a correlation between increasing donor and recipient age, decreasing
      preoperative cell density and loss of endothelial cells 2 years after penetrating
      keratoplasty. Patients with the diagnosis keratoconus should also receive
      transplants with higher donor age.

PMID- 11450480
TI  - [Predictors of recurrent basalioma of the eyelids and periorbital region].
AB  - BACKGROUND AND OBJECTIVES: Basal cell carcinoma is the most common malignant
      tumour of the eyelids but surgical excision in the eyelid region is often in
      conflict with preserving lid function. The purpose of this study was to identify
      factors predictive of basal cell carcinoma recurrence to improve pre- and
      postoperative planning. PATIENTS AND METHODS: A total of 153 patients with basal
      cell carcinomas without recurrence of at least 5 years were compared with 45
      primary lesions of recurrent basal cell carcinomas. Using bivariate correlations
      and multiple regression analysis, clinical factors were analysed for their value
      to predict recurrence. RESULTS: Incompletely excised tumours were most likely to
      recur and re-excised tumours had a higher recurrence rate than primary completely
      excised tumours. Morphea or sclerosing lesions had a significantly higher
      tendency to recur than nodular lesions. The recurrency rate decreased with the
      tumours distance from the lid margin. Based on these factors the calculated risk
      of a patient was between 47% and 63%, with an estimated risk of recurrence of
      50%. CONCLUSIONS: Predicting recurrence using these factors, is not possible in a
      clinically relevant dimension. So all patients with a basal cell carcinoma of the
      eyelids or periocular region must be re-examined regularly to detect recurrent
      lesions as early as possible. Of all recurrences, 89% occurred within the first 5
      postoperative years, therefore this should be regarded as the minimal sufficient
      follow-up time.

PMID- 11450481
TI  - [Indications and prognosis of dacryocystorhinostomy in childhood. A clinical
      study 1970-2000].
AB  - BACKGROUND: Dacryocystitis in infants is a serious complication of congenital,
      but seldom of acquired nasolacrimal duct obstructions. If conservative treatment
      fails, dacryocystorhinostomy (DCR) appears to be effective. The indications,
      special clinical history and results will be reviewed. PATIENTS AND METHODS: From
      1/1970 to 2/2000, a total of 72 children (56 male, 16 female) with persistent
      dacryocystitis (18 bilateral) were treated surgically by DCR and were
      continuously documented. The patients ranged in age from 10 months to 14 years
      old (mean age 4.9 years). Included in our study were 66 children (52 male, 14
      female) with 84 surgically treated lacrimal ducts (46 right eyes, 38 left eyes)
      who underwent control examinations. RESULTS: The cause of dacryocystitis was
      congenital obstruction in 63 children and trauma (maxillary fracture) in 3
      children, respectively. Of these, 20 children (30.3%) had additional anomalies of
      the lacrimal system, 21 (31.8%) systemic malformations and 8 out of the 66
      children (12.1%) had a family history of nasolacrimal duct obstruction. Since
      1985 the surgical procedures have been performed under microsurgery conditions
      and since 1998 sometimes with a transcanalicular laser-assisted technique. We
      found a functional success rate (with complete resolution of symptoms) of 90.4%
      (76 out of 84 lacrimal ducts) over follow-up periods ranging from 1 month to 12
      years (average 1.6 years). CONCLUSION: Patients with persistent dacryocystitis
      due to congenital nasolacrimal duct obstruction have a prevalence of further
      nasolacrimal abnormalities and a family history. The dacryocystorhinostomy of
      infants requires minimal invasive (sometimes laser-assisted) techniques. In the
      case of persistent dacryocystitis, DCR is indicated after the age of 1 year and
      has the same success rate in infants as in adults (90-95%).

PMID- 11450482
TI  - [Neuroprotection in glaucoma. What is the current status?].

PMID- 11450483
TI  - [Possibilities of broad spectrum analysis of gene expression patterns with cDNA
      arrays].
AB  - BACKGROUND: Our knowledge about the molecular and genomic background of diseases
      has expanded dramatically in the recent past and cDNA microarrays now provide the
      opportunity to simultaneously analyse the expression of thousands of genes. This
      could pave the way towards a systematic exploration of the pathogenetic principle
      of ophthalmological diseases which could lead to the identification of key
      disease-specific molecules that will be useful as diagnostic marker or serve as
      therapeutic targets. MATERIALS AND METHODS: Various strategies for cDNA
      microarray analysis are reviewed, including different commercially available
      arrays (microarrays on glass and arrays on nylon filters) as well as methods for
      analysing the unprecedented large amounts of data from a single experiment.
      Possible applications for research and clinical applications in ophthalmology are
      discussed. RESULTS: The cDNA microarray-based technology allows the rapid and
      cost-effective screening of gene expression without a priori knowledge about
      which gene might be of interest. Here, we discuss how the analysis of gene
      expression as whole profiles instead of the conventional focus on an individual
      gene may offer new insights into the fundamental nature of the pathogenesis of
      complex diseases using the example of early diabetic retinopathy. CONCLUSION: To
      date, the gene-array technology is still largely a laboratory procedure and has
      not yet been used in the clinical setting. However, in clinically oriented basic
      research, it will allow a more encompassing analysis of disease processes and
      thus lead to the identification of important diagnostic tools and potential drug
      targets in ophthalmological diseases.

PMID- 11450484
TI  - [Acute zonal occult outer retinopathy (AZOOR)].
AB  - BACKGROUND: The "white dot syndromes" are a clinically heterogeneous group of
      inflammatory chorioretinopathies with an inconsistent classification. It is not
      yet clear if they represent distinct entities or if they are only different forms
      of the same basic disease. CASE REPORT: A 53-year-old female patient presented
      with unilateral photopsia and reduced vision in the left eye. Funduscopy of the
      left eye showed peripapillary confluent whitish infiltrates in the deep retinal
      layers with corresponding enlargement of the blind spot. Slow progression of the
      lesions was observed followed by the development of subretinal fibrosis in the
      macula. The ERG was reduced in the left eye. In both eyes there were small round,
      partly confluent areas of RPE atrophy in the lower fundus periphery without
      inflammatory reaction in the vitreous body or anterior chamber. CONCLUSION: The
      presented case shows overlapping features of acute zonal occult outer retinopathy
      (AZOOR), multifocal choroiditis and diffuse subretinal fibrosis and uveitis. This
      case and other previously described cases with overlaps between different
      clinical entities support the theory that clinically different inflammatory
      chorioretinal diseases may represent parts of a spectrum of one common disease.

PMID- 11450485
TI  - [Mirror eyeglasses in Bechterew disease].

PMID- 11450486
TI  - [Squint amblyopia as a masking symptom. Juvenile pilocytic astrocytoma of the
      optic nerve (WHO grade I)].

PMID- 11450487
TI  - [Ocular cicatricial pemphigoid].

PMID- 11450488
TI  - The heterozygous 20210 G/A genotype prevalence in patients affected by central
      and branch retinal vein occlusion: a pilot study.
AB  - BACKGROUND: Several inherited conditions have been associated with an increased
      or decreased incidence of retinal vein occlusion (RVO). The A allele in the 20210
      G/A prothrombin gene has been found to be associated with systemic venous
      thrombosis. The aim of this study has been to verify the prevalence of this
      mutation in patients affected by central RVO (CRVO) or branch RVO (BRVO).
      METHODS: A retrospective study was carried out on 100 consecutive patients
      suffering from RVO, more than 50 years old, unaffected by systemic diseases known
      to be associated with markedly increased RVO occurrence. We determined the
      frequency of this mutation by performing mutagenised amplification of exon 14
      followed by restriction analysis of the amplified DNA fragment. RESULTS: The
      overall frequency of prothrombin 20210A allele in RVO patients was 6.0%. All
      heterozygous patients had suffered from CRVO. In this study subgroup, the
      frequency of the 20210 G/A prothrombin heterozygosis was 12.0%. The difference in
      the frequency of this the genetic variant between the CRVO and BRVO groups was
      statistically significant. None of the conventional RVO risk factors were
      statistically related to the occurrence of the disease in either the CRVO or the
      BRVO subgroup. CONCLUSION: The prevalence of the prothrombin 20210A mutation
      observed in CRVO patients is significantly higher than in the normal Italian
      population. Moreover, the prevalence is significantly greater in CRVO than in
      BRVO patients. These results raise the possibility that the prothrombin 20210A
      variant may be considered as a risk factor for CRVO.

PMID- 11450489
TI  - Variability of tear protein levels in normal young adults: diurnal (daytime)
      variation.
AB  - PURPOSE: To investigate the diurnal variation (daytime changes) of human tear
      protein levels, and to compare the results obtained by two sampling methods, the
      yawn and eye-flush methods.

PMID- 11450490
TI  - Vitrectomy results in diabetic macular oedema without evident vitreomacular
      traction.
AB  - PURPOSE: To determine the effectiveness of vitrectomy in eyes with diabetic
      macular oedema without evident traction from a thickened vitreous membrane.
      METHODS: Twenty-one consecutive eyes from 19 patients with diabetic macular
      oedema that had undergone vitrectomy were analysed retrospectively. All eyes had
      an attached posterior hyaloid membrane in the macular region, but without
      thickening and without evident traction on the macula. A standard pars plana
      vitrectomy with the creation of a posterior vitreous detachment was performed.
      RESULTS: Median duration of macular oedema at the time of vitrectomy was
      approximately 11.0 months (range 2-36 months). The median preoperative best
      corrected visual acuity of 0.08 (range hand motions/0.003 to 0.4), improved by 5
      lines to a median final postoperative best-corrected visual acuity of 0.25 (range
      0.025-0.5) (P = 0.001). Seven eyes without preoperative macular photocoagulation
      had a median visual acuity improvement of 77%, range 32-400%, while 12 eyes with
      preoperative macular laser treatment had a median visual acuity improvement of
      14.8%, range 0-66.1% (P = 0.02, CI 95%, after multivariate regression analysis).
      In all 21 eyes, macular oedema was no longer visible on microscopic examination
      after a median period of 3.0 months (range 1-9 months) after vitrectomy.
      CONCLUSIONS: In eyes with diabetic macular oedema without evident macular
      traction from a thickened vitreous membrane, vitrectomy resulted in the
      resolution of macular oedema, with an improvement in visual acuity in the
      majority of cases. Eyes without preoperative macular photocoagulation had a
      significantly higher percentage visual improvement than eyes without preoperative
      macular laser treatment. A randomised controlled prospective trial of primary
      vitrectomy versus macular photocoagulation is needed to determine the role of
      vitrectomy as treatment modality for diabetic macular oedema.

PMID- 11450491
TI  - Blood flow of the optic nerve head and peripapillary retina in exfoliation
      syndrome with unilateral glaucoma or ocular hypertension.
AB  - BACKGROUND: The purpose was to study whether any differences exist in the optic
      nerve head (ONH) and peripapillary retinal blood flow between the two eyes of
      patients with unilateral exfoliation glaucoma or ocular hypertension (OHT) with
      exfoliation syndrome. METHODS: This cross-sectional study included 50 patients.
      All had exfoliation syndrome with glaucoma or OHT in one eye, and these eyes
      comprised the study group. The fellow eyes, all normotensive, comprised the
      control group. Blood flow was measured with scanning laser Doppler flowmetry in
      the lamina cribrosa region, in the rim area, and on the peripapillary retina.
      Multiple linear regression analyses were used to identify any associations
      between different factors and differences in flow. RESULTS: Flow in the rim area
      was significantly higher in the study eyes than in the control eyes, with a mean
      difference of 172 arbitrary units (P = 0.001). The difference of 40 units in the
      laminar area was of borderline significance (P = 0.065) and no significant
      difference was found in the peripapillary retina (P = 0.530). In the study eyes,
      blood flow of the ONH lamina and rim area decreased with increasing glaucomatous
      damage, and treatment with topical timolol was associated with reduced blood flow
      in the lamina cribrosa and rim area. Perfusion pressure was associated only with
      flow in the peripapillary area (P = 0.021). CONCLUSIONS: Advanced glaucomatous
      damage was associated with reduced flow both in the lamina cribrosa and the rim
      area but not in the peripapillary retina. Treatment with topical timolol was
      associated with decreased flow in the ONH.

PMID- 11450492
TI  - Localization of alpha integrin subunits in the neural retina of the tiger
      salamander.
AB  - BACKGROUND: Integrin receptors mediate cell-extracellular matrix interactions and
      regulate many events, including cell growth, proliferation, and differentiation.
      Retinal integrins are incompletely understood, although these receptors are
      potentially important factors in normal retinal function and pathology. METHODS:
      Immunocytochemistry was used to localize alpha integrin subunits 1-6 in the
      neural retina. RESULTS: Each alpha integrin subunit had a unique distribution in
      the retina, although there was considerable overlap among subunits. The alpha 1
      subunit was broadly distributed throughout the retina, with some presumptive
      ganglion cells showing enriched labeling. The alpha 2 subunit was present on all
      retinal cell bodies, but was reduced in synaptic layers. The alpha 3 subunit was
      present in synaptic layers, Muller cells, and some cone and amacrine cells. The
      alpha 4 subunit was broadly distributed in the nuclear layers but was reduced in
      synaptic layers. The alpha 5 subunit was broadly expressed in the nuclear and
      synaptic layers with enriched labeling in the outer plexiform layer. Labeling for
      the alpha 6 subunit was restricted to the outer limiting membrane and some cone
      outer segments. Double-labeling studies indicated that photoreceptor terminals
      may exhibit alpha 1 and alpha 5 subunits, while processes from second-order
      neurons may exhibit alpha 1, alpha 3, and alpha 5 subunits. CONCLUSION: Integrin
      receptors containing the alpha 1, alpha 3, and alpha 5 subunits may have
      important functions at retinal synapses, in addition to roles in the nuclear
      layers. Integrin receptors containing alpha 2, alpha 4, and alpha 6 subunits
      probably serve non-synaptic functions.

PMID- 11450493
TI  - Topological-histological investigation of the pterygium.
AB  - BACKGROUND: It is a wide-spread assumption, never proven scientifically, that the
      pterygium is a duplication of the conjunctiva, with an intervening gap at the
      limbus. We therefore conducted a histological reinvestigation, primarily to
      clarify the topological relation between normal bulbar tissue and lesion.
      METHODS: Excised pterygia were prepared for light microscopy and embedding in
      paraffin. Two pterygia were serially sectioned, and samples of 49 others were
      removed, sectioned and stained (stains: H&E, alcian blue, toluidine blue, PAS;
      antibody: cytokeratin 18). RESULTS: The pterygium is an epithelium-covered
      protuberance of connective tissue, projecting over the normal surface of the
      eyeball; it consists of a base, which extends in the direction of growth, and
      lateral lobes. It is therefore impossible to insert a probe all the way under a
      pterygium. The bulbar tissue adjacent to the pterygial protuberance can likewise
      be histologically altered. That is, a narrow layer of connective tissue, well
      supplied with capillaries, may be present in the corneal section of the pterygium
      between Bowman's layer and the epithelium. CONCLUSION: Histological alterations
      of the stroma predominate quantitatively over those of the epithelium. The
      topographical anatomy of the lesion and the fact that bulbar tissue is modified
      along with the pterygium should be taken into account when excision is
      undertaken. We predict that if all the altered tissue is removed, the rate of
      recurrence will be reduced.

PMID- 11450494
TI  - The influence of pro-inflammatory cytokines on human retinal pigment epithelium
      cell receptors.
AB  - PURPOSE: To investigate the mRNA expression of the receptors for tumour necrosis
      factor alpha (TNFRp55, TNFRp75), interferon gamma (IFN gamma R alpha, IFN gamma R
      beta), interleukin 10 (IL-10R, CRFB4) and transforming growth factor beta (TGF
      beta RII) on human retinal pigment epithelium (RPE) cells and to modulate this
      expression with the pro-inflammatory cytokines TNF-alpha and IFN-gamma as
      stimulators. METHODS: The cells were cultured in the presence of TNF-alpha (10
      ng/ml), IFN-gamma (1000 U/ml) or a combination of both for 24 h, 48 h and 72 h.
      The total RNA was prepared, and the receptor mRNA expression was investigated by
      the reverse-transcription polymerase chain reaction method. The changes in mRNA
      expression during the modulation were quantified by the ribonuclease protection
      assay. RESULTS: The mRNA for TNFRp55, TNFRp75, IFN gamma R alpha, IFN gamma R
      beta, CRFB4 and TGF beta RII was constitutively expressed in vitro. IL-10R mRNA
      was detected in neither unstimulated nor stimulated RPE cells. Especially the
      mRNA of the TNF-Rp75 was up-regulated, mainly by IFN-gamma or the combination of
      both stimulators. CONCLUSION: Our results demonstrate that human RPE cells
      express the mRNA of different cytokine receptors and the expression may be
      partially modulated by pro-inflammatory cytokines. This may show that RPE cells
      act as corresponding cells not only in vitro, but also in inflammation and
      immunological processes in the eye. In this connection it could be hypothesised
      that activated RPE cells play a stimulating role in addition to the known
      suppressive one.

PMID- 11450495
TI  - Effect of ultraviolet radiation on melanogenesis in four different types of
      cultured bovine ocular pigmented cells.
AB  - BACKGROUND: Ultraviolet radiation is thought to play a causative role in various
      ocular diseases such as macular degeneration, cataract, and possibly melanomas.
      Since most of the energy is absorbed by pigmented cells, the aim of this study
      was to examine and compare the reactions of different ocular melanocytic cells to
      ultraviolet light in vitro. MATERIALS AND METHODS: Bovine iris melanocytes,
      choroidal melanocytes, iris pigment epithelial cells, and retinal pigment
      epithelial cells were isolated and cultured. Semiconfluent cultures were exposed
      to ultraviolet radiation (280-380 nm). Cell number and melanin content were
      measured 10 days after radiation. Selected samples were examined by transmission
      electron microscopy. RESULTS: Following irradiation with ultraviolet light for 30
      s, 60 s, and 120 s, the number of cells in culture decreased markedly. In
      contrast, total melanin content in the cultures of iris melanocytes, choroidal
      melanocytes, and iris pigment epithelial cells did not decrease despite the
      reduced number of cells. This finding suggested an increase in melanin per cell.
      However, the increase in average melanin content observed was not due to
      melanogenesis, because treatment with the melanogenesis inhibitor alpha-methyl-p
      tyrosine did not reduce the melanin content of the cultures and electron
      microscopic examination showed no morphological evidence of increased
      melanogenesis. CONCLUSION: In vitro, there was no convincing evidence of
      ultraviolet radiation-induced melanogenesis in ocular pigmented cells. Thus, it
      seems that ultraviolet radiation is a selection factor: more densely pigmented
      cells survive the treatment better than less pigmented cells.

PMID- 11450496
TI  - Muscarinic receptors of the M2 subtype in human and bovine trabecular meshwork.
AB  - BACKGROUND: The trabecular meshwork is a tissue actively involved in the
      regulation of intraocular pressure via contractile mechanisms. The present study
      was performed to investigate the effects of muscarinic m2-receptor antagonists on
      trabecular meshwork contractility and to identify the m2 muscarinic receptor in
      human and bovine trabecular meshwork cells. METHODS: Isometric tension
      measurements of bovine trabecular meshwork strips were performed using a custom
      made force length transducer. Western blot and immunoprecipitation analysis was
      used to detect the m2-receptor proteins in membrane preparations of human and
      bovine trabecular meshwork cells. RESULTS: Immunoblotting results showed the
      expression of an m2-receptor protein band at 56 kDa in both human and bovine
      trabecular meshwork cells. Two different m2-receptor antagonists were tested on
      trabecular meshwork contractility. After carbachol-induced contraction (10(-6) M
      set to 100% contractile force), specific m2-receptor antagonists were applied. 3
      alpha-Chloroimperaline (10(-6) M) had no effect on the maximal carbachol-induced
      contraction in trabecular meshwork strips. Methoctramine induced a significant
      relaxation at concentrations of 10(-7), 10(-6) and 5 x 10(-6) M even in the
      presence of m1- and m3-receptor antagonists. CONCLUSION: These data indicate that
      in addition to the m3-receptor subtype present in the trabecular meshwork this
      tissue also features the m2 receptor. This receptor is partly involved in the
      regulation of trabecular meshwork contractility, suggesting that outflow facility
      might be influenced through this receptor.

PMID- 11450497
TI  - Stickler syndrome and vitreoretinal degeneration: correlation between locus
      mutation and vitreous phenotype. Apropos of a case.
AB  - BACKGROUND: Autosomal dominant vitreoretinopathies are characterized by genetic
      heterogeneity. Structural mutations in COL2A1 are the most frequent cause of
      Stickler syndrome with ocular involvement. The affected patients have a
      characteristic vitreous alteration, so-called membranous vitreous, or type 1
      vitreous phenotype. Recently a novel mutation in the gene encoding the alpha 1
      chain of type XI collagen (COL11A1) was reported in rare Stickler pedigrees, with
      a different, so-called beaded or type 2 vitreous phenotype. METHODS: Five
      patients of an Italian family affected by high myopia, high frequency of retinal
      detachment, and other systemic stigmata evocative of Stickler syndrome (flat
      midface, depressed nasal bridge, short nose, spondyloepiphyseal dysplasia and
      osteoarthritis) were studied. Genetic investigations were also performed,
      considering three candidate loci for Stickler syndrome and Wagner syndrome
      (COL2A1, COL11A1, WGN1). RESULTS: Segregation analysis was performed utilizing
      polymorphic markers. COL2A1 and WGN1 segregations were excluded; COL11A1 showed
      concordance with the disease. The vitreous phenotype of the family was a typical
      type 1 or "membranous" vitreous, although all the previously reported COL11A1
      related Stickler syndromes had always shown the type 2 or "beaded" vitreous
      phenotype. CONCLUSIONS: The clear presence of the type 1 or "membranous" vitreous
      phenotype in our family, despite the probable mutation in the COL11A1 gene,
      suggests greater phenotypical heterogeneity and a more extensive mutation
      spectrum, even of the COL11A1 gene, than previously thought, explaining the basis
      for the different vitreous phenotypes seen in Stickler syndrome.

PMID- 11450498
TI  - Apoptosis mediating ligand-receptor systems in human Tenon fibroblasts.

PMID- 11450499
TI  - Family and disease management in young type 1 diabetic patients.
AB  - The main objectives of type 1 diabetes mellitus (DM) management include keeping
      glycemia levels within the euglycemic range to prevent complications. Daily self
      monitoring is an important problem for many diabetic patients, particularly for
      adolescents. The aim of this study was to evaluate the determinants of poor daily
      self-monitoring, focusing on the patients' parents' perception of the problem. In
      order to evaluate parents' awareness of their children's disease-monitoring
      status, we carried out a cross-sectional investigation of a sample of children
      and adolescents from a population-based register, with the corresponding
      population of parents. To collect our data, we used a 33-item questionnaire,
      separately administered by diabetologists to both parents and children. We
      estimated the concordance with respect to patients' and parents' answers.
      Adolescents followed their overall medical prescriptions more regularly (48.8%)
      than children (29.7%), but most frequently they forgot to use glycemic tests
      (adolescents 42.4%, children 29.7%). A major duration of disease affected HbA1c
      levels (values > 8%) of patients younger than 14 years (pFisher = 0.016). Our
      results indicate a worse compliance of adolescents with respect to children in
      attending to daily self-monitoring, not just regarding daily glycemic levels but
      also the course of daily activities such as going to school, studying, working,
      and simulating symptoms and signs of hypo-hyperglycemia. Parents mostly ignored
      their child's self-monitoring status and the related motivations.

PMID- 11450500
TI  - Lipid peroxidation and scavenging enzyme activity in streptozotocin-induced
      diabetes.
AB  - The aim of this study was to evaluate lipid peroxidation and scavenging enzyme
      activity in streptozotocin-induced diabetes, and then to establish whether
      moderate doses of nonenzymatic antioxidant vitamin E play a role in the
      antioxidant defence system in diabetic pregnant rats and their offspring. The
      study group consisted of 30 normal female Wistar rats, which were given a single
      dose of streptozotocin (40 mg/kg) and were mated 7 days later. Subsequently, the
      diabetic animals were divided into two matched groups: the first supplemented
      with vitamin E (30 mg/100 g chow), and the other fed with a standard diet lacking
      vitamin E. Controls consisted of 15 pregnant rats. On the first day after
      delivery, the rats were decapitated and homogenates of maternal liver and uterus
      as well as neonatal lungs and liver were prepared. Then the following parameters
      were measured: malondialdehyde (MDA) concentrations in the homogenates and blood
      serum, glutathione (GSH) levels, the activity of CuZn-superoxide dismutase (SOD)
      and glutathione peroxidase (GPx), and glycaemia. The neonates of diabetic rats
      were smaller than the healthy ones and serum glucose concentration was markedly
      higher in the diabetic animals. MDA levels were significantly increased, whereas
      GSH, SOD and GPx were markedly diminished in the diabetic adult rats and their
      offspring in comparison to the control group. In the animals supplemented with
      alpha-tocopherol, MDA concentrations were significantly lower, GSH content and
      SOD activities were markedly elevated most tissues studied, whereas GPx remained
      unchanged. We conclude that, by monitoring the activity of selected scavenging
      enzymes, information on ongoing biological oxidative stress and thereby on the
      fetus/neonate status may be obtained. Our results suggest that diabetic pregnant
      rats and their neonates are exposed to an increased oxidative stress and that
      vitamin E supplementation may reduce its detrimental effects.

PMID- 11450501
TI  - The influence of the ACE inhibitor lisinopril on the glomerular metabolism of
      proteolytic enzymes in diabetic rats.
AB  - Clinical studies indicate a nephro-protective effect in conjunction with the use
      of ACE inhibitors. This study's aim was to determine whether ACE inhibitors
      influence the metabolism of glomerular cells in addition to their known
      hemodynamic effects. Streptozotocin diabetic rats were treated with lisinopril
      (DLis 1.5 mg/l water), or hydralazine (Dhyd, 50 mg/l water) over 4 weeks.
      Untreated diabetic rats (DC) and non-diabetic rats (C) served as controls. After
      four weeks of treatment, urinary excretion of albumin, blood pressure and
      metabolic control (Glyc-Hb) were measured. After treatment glomeruli were
      isolated and homogenized, and beta-NAG and total proteolytic activity against
      azocasein were measured. Glycated hemoglobin levels were similar in all diabetic
      groups (DC, 12%, Dhyd, 10%; DLis 11%). Blood pressure of DLis rats (79 +/- 3
      mmHg) and DHyd rats (46 +/- 2 mmHg) was lower than that of DC rats (111 +/- 3
      mmHg). Urinary albumin excretion of diabetic groups was lowest in DLis. Diabetic
      rats showed a decrease in glomerular beta-NAG (10 vs. 60.5 U/g protein) and total
      proteolytic activity against azocasein (148 vs. 170 U/mg protein hour) compared
      to non-diabetic rats. Lisinopril increased beta-NAG (30 vs. 14 U/g protein) and
      total proteolytic activity (160.5 vs. 141.5 U/mg protein hour) compared with
      hydralazine. Our study confirms that the nephro-protective effect of ACE
      inhibitors is partially due to modulatory effects on the metabolism of basement
      membrane proteins.

PMID- 11450502
TI  - Anti-insulin receptor autoantibodies in a patient with type B insulin resistance
      and fasting hypoglycemia.
AB  - We studied a patient with systemic lupus erythematosus and type B insulin
      resistance who showed almost complete normalization of postprandial plasma
      glucose in 3 months and a transient occurrence of fasting hypoglycemia from day
      35 (i.e. the 35th day of hospitalization) to day 77. To determine the clinical
      relevance of the biological ability of anti-insulin receptor antibodies (anti
      IRAb), we made multiple preparations of the patient's dialyzed serum and IgG.
      Dialyzed serum prepared on day 1 showed 95% inhibition of insulin binding. The
      binding inhibition was, however, decreased parallel to the normalization of
      insulin sensitivity. For 2DG uptake, 6.2 microM IgG purified on 3 different days
      (days 7, 35 and 78, designated IgG-NOV, -JAN, and -FEB, respectively) stimulated
      2DG uptake into CHO-hIR at 3.4-, 3.1-, and 1.5-fold, respectively.
      Phosphotyrosine immunoblotting revealed that apparent insulin receptor
      autophosphorylation was visible only with IgG-NOV, not with the IgG-JAN or -FEB.
      Mutation of tyrosine-960 or lysine-1018 of the insulin receptor failed to
      transduce the IgG's stimulatory effect. IgG-NOV was not able to stimulate the
      autophosphorylation of the human IGF-I receptor. In the present study, the
      insulin binding inhibitory activities of the dialyzed sera prepared at different
      time points were shown to be altered parallel to insulin sensitivity in vivo.
      Stimulatory activities of the patient's IgG were, however, discordant for the
      occurrence of fasting hypoglycemia observed in vivo. Other pathogenic factors or
      mechanisms in addition to the insulin-like action of the anti-IRAb may be also
      required to fully understand the development of fasting hypoglycemia in type B
      insulin resistance.

PMID- 11450503
TI  - Summer camps for diabetic children: an experience in Antalya, Turkey.
AB  - To evaluate the effectiveness of diabetic summer camps with objective parameters,
      we examined the data relative to summer camps organized by our department in
      Antalya in the last two years. The duration of the camps was 10 days. Twenty
      eight diabetic children with an average age of 13.6 +/- 2.9 years (range 8-20)
      participated in the first camp, fourteen of whom participated in both camps. The
      medical personnel consisted of three pediatric endocrinologists, one
      psychologist, two diabetes nurses and two dietitians. Despite a mean 10%
      reduction in insulin dosage and 10% increment in daily calorie intake at the
      beginning of the camp, hypoglycemia was common (mean, 2.4 hypoglycemic episodes
      per subject). Ketoacidosis was not encountered in any of the subjects during and
      after camps. An increment in weight in children whose weights, with respect to
      heights, were under the ideal weight and a decrement in weight of overweight
      children were observed at the end of the first camp. A significant improvement in
      knowledge and self-management of the disease was noted at the end of the camps.
      Improvement in nutrition and diabetic knowledge level of the children who
      participated in these consecutive camps was more obvious in the second compared
      with that in the first camp. No significant change in HbA1c level was observed at
      follow-up. In conclusion, summer camps are an invaluable way for diabetic
      children to gain skills in managing their disease.

PMID- 11450504
TI  - Mechanisms of acute and chronic hypoglycemic action of gliclazide.
AB  - An extrapancreatic effect of sulfonylureas has been postulated. However, in vivo
      results have been disputed because the amelioration of insulin action that
      follows sulfonylurea may represent the relief from glucose toxicity rather than a
      direct effect of the drug. Therefore, we studied the hypoglycemic action of
      gliclazide acutely and after 2 months of therapy in seven type 2 diabetic
      patients. All patients received a 240-minute i.v. glucose infusion with [3
      3H]glucose. In a random order, 160 mg gliclazide (study 1) or placebo (study 2)
      was given orally before glucose infusion. Finally, the effect of 160 mg
      gliclazide was reassessed after a two-month treatment with the same sulfonylurea
      (80 mg t.i.d.). Basal plasma glucose, insulin, C-peptide and endogenous glucose
      production (EGP) were similar before the two initial studies. During glucose
      infusion, EGP was more suppressed after gliclazide in spite of comparable
      increase in plasma insulin and C-peptide. After the two-month therapy, basal
      plasma glucose levels and HbA1c were lower while plasma insulin and C-peptide
      were higher with respect to baseline (p < 0.05). Gliclazide further reduced
      plasma glucose, the incremental area above baseline, and EGP during glucose
      infusion, while plasma insulin and C-peptide achieved higher plateaus (p < 0.05).
      When data were pooled, plasma glucose concentration and EGP correlated both in
      the basal state (r = 0.71) and during the last hour of glucose infusion (r =
      0.84; both p < 0.05). These data suggest that gliclazide enhances the suppression
      of EGP induced by insulin and that this effect is greater with chronic treatment
      because of concomitant improvement of insulin secretion.

PMID- 11450505
TI  - Evaluation of T-cell receptor CD3+ gamma delta in gestational diabetes mellitus.
AB  - Few studies have shown a significant increase of CD3+ T-cell receptor (TCR) gamma
      delta in the early phases of type 1 diabetes. We wished to determine if CD3+ TCR
      gamma delta is involved in the pathogenesis of gestational diabetes mellitus
      (GDM). We studied 29 GDM patients and 21 normal pregnant women. Lymphocyte
      subpopulations (CD3+ TCR alpha beta, CD3+ TCR gamma delta), islet cell antibodies
      (ICA), glutamic acid decarboxylase antibodies (GAD) and protein tyrosine
      phosphatase antibodies (IA2-Ab) were evaluated in all patients. The percentage of
      CD3+ TCR gamma delta was significantly higher in GDM women than in the control
      group (5.1 +/- 2.9% vs 3.7 +/- 1.7%; p < 0.05). No abnormalities of the other
      lymphocyte subpopulations were found. All subjects were negative for ICA; 2 GDM
      patients were positive for GAD, but no relationship was found between GAD
      positivity and CD3+ gamma delta levels in these 2 patients. Further follow-up
      studies of these patients are required to verify if the CD3+ TCR gamma delta
      receptor is a useful marker for diabetes development.

PMID- 11450506
TI  - Hospitalization of diabetics 12-30 years of age in Kuwait: patients'
      characteristics, and frequency and reasons for admission.
AB  - In an observational study, we investigated the patient characteristics, frequency
      and reason for admission in young diabetics (aged 12-30 years) admitted at a
      major hospital in Kuwait. During the 3-year period, there were 88 evaluable
      admissions in 59 patients (30 males, 29 females; 34 Kuwaiti nationals, 25
      expatriates). Admissions were more frequent in females than males: overall (55
      vs. 33, p < 0.05), in the sub-group aged 12-19 years (31 vs. 10, p < 0.05), and
      in Kuwaitis (41 vs. 17, p < 0.05). The female preponderance reflected a higher re
      admission rate than in males (1.9 vs. 1.1, p < 0.05). Females also had longer
      duration of diabetes (median, 3 vs. 0.75 years, p = 0.01). The main causes of
      hospitalization were acute hyperglycemia with ketonuria (75 admissions) or with
      established ketoacidosis (DKA) in 35 admissions. Hypoglycemia was not a cause in
      any patient. Female excess was also observed in those with DKA (23 vs. 12 in
      males, p > 0.05). Non-adherence to insulin therapy was the most common
      identifiable cause of DKA (11/35) and infection was a factor in only 2 cases.
      Among hospitalized young diabetic patients in Kuwait, adolescent females with
      Kuwaiti nationality were most commonly affected. Studies on psychosocial
      disorders in young diabetic patients could be beneficial and may help to improve
      metabolic control and reduce diabetes-related admissions for young diabetics in
      Kuwait and other countries of the region.

PMID- 11450507
TI  - Postabsorptive muscle protein metabolism in type 1 diabetic patients after
      pancreas transplantation.
AB  - Insulin was shown to induce protein anabolism in vivo mainly by inhibiting
      proteolysis. Heterotopic pancreas transplantation in type 1 diabetes mellitus is
      characterized by peripheral hyperinsulinemia due to systemic rather than portal
      insulin delivery. Therefore, we studied the postabsorptive muscle protein
      metabolism in type 1 diabetic patients with or without pancreas transplantation.
      The forearm balance technique was performed in 9 type 1 diabetic patients on
      exogenous insulin treatment, in 4 type 1 diabetic patients following successful
      pancreas transplantation and in 6 healthy volunteers. Labelled leucine and
      phenylalanine were infused to quantify whole-body and muscle protein synthesis,
      respectively. In the postabsorptive state, whole-body protein synthesis (leucine
      kinetics) was similar in pancreas-transplanted patients and controls. In
      contrast, muscle protein synthesis tended to be less negative in pancreas
      transplanted patients with respect to type 1 diabetic patients and healthy
      volunteers. The present data suggest that recipients with peripheral insulin
      delivery and chronic hyperinsulinemia are characterized by a preferential
      stimulation of protein synthesis in muscle rather than in the splanchnic
      district. When insulin was infused acutely, while maintaining euglycemia, the
      whole-body and muscle protein synthesis rates were approximately halved in type 1
      diabetic patients with and without pancreas transplantation. We conclude that
      pancreas transplantation is able to normalize basal and insulin-stimulated
      protein metabolism. Chronic hyperinsulinemia counteract steroid-induced protein
      degradation by means of a mild, but persistent stimulation of muscle protein
      synthesis.

PMID- 11450508
TI  - [How high is the rate of spontaneous healing of sudden deafness? Comments on the
      contribution "Spontaneous healing of sudden deafness"].

PMID- 11450509
TI  - [Ginkgo biloba: ineffective against tinnitus?].

PMID- 11450510
TI  - [Ames test as biomarker].
AB  - BACKGROUND AND OBJECTIVE: The incidence of squamous cell carcinomas in the upper
      aerodigestive tract has increased worldwide. The main risk factors are chronic
      tobacco and alcohol consumption. The detection of high-risk persons is important
      because early diagnosis of these tumors provides a good chance for permanent
      healing. Biomonitoring programs may help to give precise information about the
      individual cancer risk among smoking and drinking persons. The aim of this study
      was to evaluate the Ames test as a biomarker to detect the genotoxicity of
      saliva. PATIENTS AND METHODS: Saliva specimens of 131 probands were investigated
      for their genotoxic effects using the Ames test. RESULTS: Our results showed an
      increased trend of genotoxic activity in the saliva of smokers. A highly
      significant additional increase of genotoxicity was measured in smoking and
      drinking individuals. CONCLUSIONS: Our study shows that the Ames test could be
      used to show genotoxic effects in saliva specimens. In combination with other
      biomarkers, this test may help to develop a valid concept for detecting cancer
      endangered people.

PMID- 11450511
TI  - [Duration of middle ear ventilation after laser myringotomy with the CO2 laser
      otoscope Otoscan].
AB  - BACKGROUND: The most important principle in treating secretory otitis media (SOM)
      is ventilation of the tympanic cavity. CO2 laser myringotomy achieves this via a
      self-healing perforation whose diameter essentially determines the duration of
      transtympanic ventilation. PATIENTS, METHODS: In this study, laser myringotomy
      was performed with the CO2 laser otoscope Otoscan in a homogeneous patient
      collective comprising 81 children (159 ears) suffering from SOM. The tympanic
      intervention was combined with an adenoidectomy or a CO2 laser tonsillotomy and
      therefore performed under general insufflation anesthesia. In all ears,
      approximately 2 mm circular perforations were created in the lower anterior
      quadrants with a power of 12-15 W and a pulse duration of 180 ms. RESULTS: None
      of the children showed postoperative impairment of inner ear function.
      Otomicroscopic and videoendoscopic monitoring documented the healing process. The
      mean closure time was found to be 16.35 days (8-34 days). As a rule, an onion
      skin-like membrane of keratinized material was seen in the former myringotomy
      perforations at the time of closure. At the follow-up 6 months later the laser
      myringotomy sites appeared normal and irritation-free. Two of the tympanic
      membranes (1.6%) examined showed atrophic scar formation, one (0.8%) a
      perforation with a diameter of 0.5 mm. In 19 ears (14.7%) there was a recurrence
      of SOM within the observation period. CONCLUSIONS: Laser myringotomy competes
      with ventilation tube insertion in the treatment of SOM. It may be an useful
      alternative in the surgical management of secretory otitis media.

PMID- 11450512
TI  - [Association of silver granules with elastic fibers in amalgam reaction of mouth
      mucosa].
AB  - OBJECTIVE: Discoloration of the oral mucosa due to amalgam may appear
      histologically merely as brown pigmentation of the fibrous extracellular matrix.
      It was the aim of these investigations to identify the fibrous component that
      contains silver granules. METHODS: Biopsy specimens from seven patients with
      clinically diagnosed amalgam tattoos were investigated by light and electron
      microscopy as well as by X-ray microanalysis. RESULTS: Light microscopy revealed
      small brown discolored fibers in all specimens; in sections stained with
      Weigert's resorcinfuchsin, they appeared dark violet. Scanning electron
      microscopy revealed metallic granules associated with thin fibers; by X-ray
      microanalysis, they exhibited preferentially peaks for silver and sulfur.
      Transmission electron microscopy detected only electron-dense particles in
      elastic fibers. CONCLUSIONS: With the different morphological methods, silver
      granules of amalgam tattoos were exclusively detected within elastic fibers. This
      result indicates that granular brown discoloration of the matrix fibrils is due
      to silver impregnation of elastic fibers. Therefore, the histopathological
      diagnosis of amalgam tattoo is possible even in the absence of larger amalgam
      particles with black appearance.

PMID- 11450513
TI  - [Loudness scaling in children].
AB  - BACKGROUND AND OBJECTIVE: Loudness measurements in children have been carried out
      using different psychoacoustical methods. Besides absolute magnitude estimation
      (AME) and cross modality matching (CMM) category and non-category loudness
      scalings have been performed. However, there is a lack of systematic evaluation
      in loudness scalings with children. PATIENTS/METHODS: A clinically feasible
      categorical method is presented which was evaluated in 10 normally hearing
      children of 7 to 8 years. Furthermore, measurements with hearing disabled
      children were performed in the framework of hearing aid evaluation. RESULTS:
      Normal hearing children scaled slightly louder than a group of adult subjects
      with normal hearing. Regarding the shape of the loudness functions measured they
      were very similar. Particularly, they showed a steeper course at higher levels
      than for low input signals. Intraindividual scatter of the loudness judgements
      was larger for children than for adults. However, high correlation appeared
      between the data across test and retest. Hence, the outcome of the scalings
      appears to be sufficient reliable. CONCLUSIONS: Clinical measurements confirmed
      that the method is appropriate for children from approximately 5-10 years.
      Loudness judgements became more consistent and more subtly differentiated with
      increasing age and decreasing hearing loss. Especially with view of hearing aid
      evaluation the method can give valuable indications because of the possibility to
      directly measure individual loudness over a broad range of levels and
      frequencies.

PMID- 11450514
TI  - [Tonsillectomy with the ultrasound activated scalpel. Initial results of
      technique with Ultracision Harmonic Scalpel].
AB  - BACKGROUND: Tonsillectomy requires an efficient intra- and postoperative
      hemostasis. The ultrasonically activated scalpel (UAS) uses high-frequency
      ultrasonic energy to perform tissue dissection and coagulation simultaneously.
      The present prospective study represents the first published results of UAS in
      tonsillectomy. METHOD: 60 patients with tonsillectomy were examined in regard of
      intra- and postoperative hemostasis, wound healing and postoperative pain. Also,
      the quality of the histopathological specimen was evaluated. RESULTS: In 90% of
      tonsillectomies by UAS efficient intraoperative hemostasis did not require suture
      ligature. In 10% additional ligation was required for reason of arterial
      bleeding. Postoperative bleeding did not occur at all, wound healing was
      uneventful. Surgery related postoperative pain was not intensified. The
      histopathological evaluation of specimen was not impaired. CONCLUSION: The UAS
      offers a tissue dissection with efficacious intra- and postoperative hemostasis.
      Compared to the conventional tonsillectomy the ultrasonical technique of
      tonsillectomy has especially in children, in anaemic patients and in the surgery
      of tonsillar malignomas significant advantages.

PMID- 11450515
TI  - [Bilateral paraganglioma of the vagus nerve].
AB  - Paragangliomas are rare, usually benign tumours of the head and neck region,
      located along the cranial nerves and the big vessels. Vagus paraganglioma
      represents less than 3% of all cases of paragangliomas of the head and neck.
      Approximately 10% of vagus paragangliomas are presented as bilateral masses. We
      present the case of 75 year old female with bilateral paraganglioma, and
      papillary cancer of the thyroid gland at the time of diagnosis. Diagnostic and
      therapeutic procedures are discussed with special regard to possible
      complications.

PMID- 11450516
TI  - [Aberrant salivary gland tissue in differential diagnosis of branchiogenic neck
      cyst].
AB  - A neck fistula next to the sternocleidomastoid muscle is suspicious of a
      branchial origin. Here we report on a 29-year-old patient with a discharging
      cutaneous orifice caused by an ectopic salivary gland. The clinical and
      histological findings are demonstrated and discussed with reference to the
      literature. Surgical removal of ectopic salivary gland tissue is the treatment of
      choice. However, surgery is limited in extent compared to surgical removal of a
      branchial fistula. Our case demonstrates that an ectopic salivary gland should be
      considered in the differential diagnosis of a branchial fistula.

PMID- 11450517
TI  - [Medical manager--new role for the physician].

PMID- 11450518
TI  - [Progressive odynophagia. Hypopharynx foreign body].

PMID- 11450519
TI  - [Rehabilitation of chronic facial paralysis. 2].

PMID- 11450520
TI  - Hospitals: too much information can be too much of a good thing.

PMID- 11450521
TI  - Hang onto your hat: HIPAA is on the way.

PMID- 11450522
TI  - Even the best can't compete with M&R.

PMID- 11450523
TI  - Group releases measures for diabetes care.

PMID- 11450524
TI  - Risk management eliminated in wide-ranging program.

PMID- 11450525
TI  - ER demand still rising, endangering patients.

PMID- 11450526
TI  - [Corrosion and haemocompatibility of 316L stainless steel with electroplated Rh
      film].
AB  - In this study, surface modification by electroplating Rh on 316L stainless steel
      was carried out in order to improve the corrosion resistance and blood
      compatibility of implants. XPS was used to characterize the Rh film. The
      corrosion behavior of 316L stainless steel with electroplated Rh and non-treated
      was studied in Tyrode's biological solution. Additionally, the haemocompatibility
      of 316L stainless steel with electroplated Rh was evaluated by preliminary
      hemolysis test. The results showed that the corrosion resistance of 316L
      stainless steel with electroplated Rh was improved, and hemolysis decreased,
      which indicated that electroplating Rh can improve the blood compatibility of
      316L stainless steel.

PMID- 11450527
TI  - [Wet synthesis and characterization of fluoride-substituted hydroxyapatite].
AB  - Hydroxyapatite and fluoride-substituted hydroxyapatite powders are synthesized by
      wet method, compacted into pellets and subjected to heat treatment at 300, 600,
      900 degrees C respectively. Analysis of the fluoride-substituted hydroxyapatites
      and HA by FTIR spectroscopy indicated that with the increasing of sintering
      temperatures, the phase-pure fluoride-substituted hydroxyapatite and
      stoichiometric hydroxyapatite could be got. According to the X-ray diffraction
      analysis, the fluoride-substituted hydroxyapatite is less stable for decomposing
      into beta-Ca3(PO4)2 at the temperature of 900 degrees C. The in vitro bioactivity
      of the fluoride-substituted hydroxyapatites and hydroxyapatite heat treated at
      900 degrees C was assessed by immersion testing in simulated body fluid (SBF).
      Both scanning electron microscopy (SEM) analysis and ionic solution changes
      (Ca2+) demonstrated that the low fluoride content apatite could induce a surface
      bonelike apatite layer formation.

PMID- 11450528
TI  - [Manufacture and study of porous poly(l-lactic acid) (PLLA)/beta-tricalcium
      phosphate (beta-TCP) composite].
AB  - A promising alternative to supply bone substitutes is to develop living tissue
      substitutes based on biodegradable materials, which is called bone tissue
      engineering. One of the research high-lights of bone tissue engineering is to
      design and manufacture scaffolds for cell attaching, migrating, and
      proliferating. A process which consists of a solvent casting stage, a compression
      molding stage and a leaching stage has been used to fabricate macroporous
      composites of poly(l-lactic acid) (PLLA) and beta-tricalcium phosphate (beta
      TCP). The effects of the weight fraction of porogen--NaCl, of the weight ratio of
      PLLA to beta-TCP and of the diameters of beta-TCP on the porosities, the average
      pore diameters and the compressive yield strength and compressive modulus have
      been studied. The results showed that the porosities and the average pore
      diameters increased and the compressive yield strength and modulus decreased when
      the weight fraction went from 50% to 90%. The compressive yield strength and
      compressive modulus could be improved by changing the weight ratio of PLLA to
      beta-TCP and the diameters of beta-TCP in low-porosity composites (lower than
      70%). But high-porosity composites (90%) were not reinforced by changing the
      weight ratio.

PMID- 11450529
TI  - [Stress-strain properties of the tissue-engineered cartilage].
AB  - This study was conducted to investigate the biomechanical properties of tissue
      engineering cartilage. The compressive modulus of the collagen-chondrocyte
      constructs that had been cultured in vivo for 16 weeks and the centrifuge-tube
      cultured cartilage in vitro were measured with 5% strain. The results showed that
      the compressive moduli of the centrifuge-tube-cultured cartilage at the 4th, 8th,
      12th and 16th weeks were 0.352 MPa, 0.653 MPa, 0.233 MPa and 0.262 MPa
      respectively. The top modulus among them was at the 8th week. The compressive
      modulus of the neocartilage engineered by the collagen-chondrocyte constructs in
      vivo for 16 weeks was 10.668 MPa and reached the same order of magnitude as human
      fetal articular cartilage, but it is still under that of the human fetal
      articular cartilage actually. The culture methods should be developed further
      though the dynamic alteration of the compressive modulus of the centrifuge-tube
      cultured neocartilage is in accord with that of the GAG/DNA content ratio of the
      neocartilage.

PMID- 11450530
TI  - [The mechanical chemical attachment of artificial cartilage (PVA-hydrogel) to
      metal substrate (or underlying bone)].
AB  - The biocompatibility and tribological characteristics of PVA-hydrogel are
      excellent, but it is very difficult to make the artificial cartilage material
      (PVA-hydrogel) attach to the underlying bone. In this study, PVA-hydrogel is
      attached to the metal fibre mesh by means of micro-mechanical interlock methods
      at first, then the surface of metal fibre mesh is bonded to the underlying bone
      by the bone cement(PMMA). In this way, the artificial cartilage can be firmly
      attached to the underlying bone(or metal substrate). Microstructure analysis and
      mechanical tests show that the attachment between artificial cartilage and the
      metal substrate is firm.

PMID- 11450531
TI  - [Effect of different cultured conditions on endothelial cell and its resistance
      to the fluid imposed shear stress--a comparative study].
AB  - This study was intended to enhance the resistance of cultured endothelial cells
      (EC) to fluid shear stress and clarify the possible mechanism. A modified
      parallel plate flow apparatus was used to compare the strength between the grafts
      and the endothelial cells under shear stress condition and static condition. The
      dynamic change of cytoskeletal actin filaments and the effects of different
      adhesive proteins coated on the strength of EC adhesion to the glass were
      studied. The results showed that the number of cells retention of the shear
      stress-conditioned group was significantly larger than that of the static group.
      Precoated fibronectin and laminin significantly promoted the adherence of the EC
      cultured in a steady environment but seemed to have no effect on the EC cultured
      under flow condition. The results suggest that the vascular endothelial cell
      cytoskeleton, stress fiber and the shape of EC reorganize in response to long
      term fluid-imposed shear stress, and the endothelial cells become tightly
      adherent to the grafts.

PMID- 11450532
TI  - [Expression property of adhesive molecule ICAM-1 on vitro-cultured pulmonary
      microvascular endothelial cells under the stimuli of asthmatic serum].
AB  - It has been recognized only in the past 15 years that the major pathological
      mechanism of asthma is inflammation, which has a hallmark of focal leukocyte
      extravasation. The different recruitment behaviors of inflammatory cells depend
      on the expression of specific adhesive molecules on both leukocytes and
      endothelial cells (EC). Intercellular cellular adhesion molecule-1(ICAM-1) plays
      a major role. In the previous detailed in-vivo study of asthmatic models, we have
      proved the significant pathological increase of both the leukocyte-endothelium
      adhesion phenomenon and the ICAM-1 expression in the tissues of asthmatic lung.
      It may be due to an ICAM-1 accumulation on the microvascular endothelial cells
      and thus an enhancement of adhesion force during the course of disease. In this
      study, endothelial cells were obtained from rats by mechanical isolation of lung
      tissues and in vitro culture on glass. Confluent endothelial cells were incubated
      with serum collected from rat blood of normal and asthmatic models and were used
      for in vitro study of endothelial cell adhesion. The effect of pathological serum
      stimulation was examined on the expression of ICAM-1 of the pulmonary
      microvascular endothelial cells (PMEC). The expression of ICAM-1 on PMEC was
      measured by indirect immuno-fluorescence with flow cytometry. We found that the
      surface expression of ICAM-1 was obviously increased on serum-incubated EC as
      compared with that on the culture solution-incubated one, and that asthmatic
      serum increased the expression of ICAM-1 on EC to a peak in 4 hours and then
      decreased it rapidly, the expression level remained the same in the whole course
      when EC was treated with culture solution or normal serum.

PMID- 11450533
TI  - [Structure and function of pancreatic microcirculation].
AB  - To gain an insight into the relationship between structure and function in
      pancreatic microcirculation, observations were carried out in 9 corpse, 30
      monkeys, 24 dogs, 62 Wistar rats and 24 rabbits by the use of scanning electron
      microscopy and light microscopy with the technique of retaining microcirculatory
      dynamic and tissular information in the static specimens, and/or by intravital
      fluorescence microscopy with FITC-labeled erythrocytes. The results showed: there
      were two capillary beds destined for the endocrine and exocrine parts of pancreas
      between the intralobular arteriole and venule; the blood of pancreatic portal
      circulation flowed from the endocrine to the exocrine part; each pancreatic
      lobule was supplied by a single centrally located intralobular artery and there
      was no anastomosis between the intralobular arterioles or any of their branches,
      so they were end arteries; the physiological blood flow was about 1.18 +/- 0.05
      nl/min per capillary with stable capillary perfusion pattern; a profound
      decreased functional capillary density and capillary perfusion was observed in
      the early phase of acute pancreatitis. These results suggest that pancreatic
      lobule is a structured and functional basic unit of pancreatic microcirculation,
      insulo-acinar portal circulation represents the basic feature of the pancreatic
      microcirculation, and the intralobular arteriole, being an end artery, forms the
      anatomical basis of the pancreatic microcirculatory disturbance during acute
      pancreatitis.

PMID- 11450534
TI  - [Effect of flow shear stress on the expression of adhesion molecules of
      endothelial cells].
AB  - Adherence of various leukocytes, including monocyte, to vascular endothelial
      cells may play an important role in the development of atherosclerosis. In vivo,
      the hemodynamic shear forces have a critical effect on the surface expression of
      adhesion proteins. In order to elucidate the effect of flow shear stress on the
      expression of adhesion molecules of endothelial cells, we investigated the effect
      of flow shear stress (2.23-6.08 dyne/cm2) on the expression of adhesive
      molecules, intercellular adhesion molecule(ICAM-1), vascular cell adhesion
      molecule (VCAM-1), and E-selectin on cultured human umbilical vein endothelial
      cells(HUVECs). The expression of adhesion molecules on the surface of HUVECs
      induced by shear stress was analyzed using flow cytometry. The results showed
      that compared with stationary control, the surface expression of ICAM-1 was
      significantly increased (P < 0.05) on HUVECs after exposure to different shear
      stress (2.23, 4.20, 6.08 dyne/cm2), and it was found to be in close relationship
      with the shearing time (r = 0.992, 0.997, 0.997; P < 0.05). After exposure to
      shear(2.23 dyne/cm2), VCAM-1 expression was significant increased(P < 0.05), and
      it was positively correlated with the shearing time(r = 0.930; P < 0.05), while
      VCAM-1 expression dropped down to basal level(P < 0.05) after it was sheared at
      4.20 or 6.08 dyne/cm2, and the magnitude of the reduction of VCAM-1 expression
      was negatively correlated with the shearing time (r = -0.975, -0.989; P < 0.05).
      E-selectin expression was less sensitive to shear stress, especially at the lower
      magnitudes of shear. These results indicate that the increase of ICAM-1 and VCAM
      1 expression in endothelial cells induced by low shear stress may play a
      prominent role in the development of both inflammation and atherosclerosis.

PMID- 11450535
TI  - [Effect of radiation with 60Co on RBC membrane elastic shear modulus and membrane
      viscosity].
AB  - RBC membrane shear elastic modulus and membrane viscosity are two important
      indexes reflecting RBC membrane viscoelasticity. Their variation was investigated
      in this study after rabbits were radiated with 60Co. With a new ektacytometer, we
      measured the small deformation index (DId) and the half-time of deformation
      relaxation (t0.5) of RBC in flow field then we calculated RBC membrane shear
      elastic modulus and membrane viscosity. We found that the value of RBC membrane
      shear elastic modulus and membrane viscosity continuously increased from 0 to
      16th day then continuously decreased and tended to be stable on 60th day or so.
      The reason may lie in the variation of proportion of new and old RBC in blood and
      variation of microconformation of RBC membrane after rabbits were radiated with
      60Co.

PMID- 11450536
TI  - [Design and improvement of stenosis model in cylindrical tubal flow via pulsed
      Doppler ultrasound in vitro].
AB  - A model of disturbed flow downstream of a severe stenosis has been established
      and improved in vitro, and the relevant method and feasibility for the detection
      of flow indices are discussed via commercially available Pulsed Doppler
      Ultrasound (PDU). Detection is done temporally and spatially, upstream and
      downstream. The methodology is proved to be feasible and has good prosperity of
      clinical use.

PMID- 11450537
TI  - [Apoptosis in pressure overload-induced heart hypertrophy].
AB  - Pressure overload can result in heart hypertrophy, and induce apoptosis, but the
      phenomenon of apoptosis during the forepart of cardiomyocyte hypertrophy remains
      unclear. The aim of this study was to inquire into the process of cardiomyocyte
      apoptosis during the forepart of cardiomyocyte hypertrophy. We constructed the
      hypertrophy model by transverse aortic constriction of male SD rat. The apoptosis
      ratio was detected by TUNEL method and FCM. The result demonstrated that
      hypertrophy indexes increased with the time of constriction, reached the highest
      level at day 7, maintained that level, and then decreased at day 91. The
      apoptosis ratio of cardiomyocyte at day 4 was higher than that at day 0 detected
      by FCM method, and the ratio at day 7 was markedly lower than that at day 4.
      After day 28, the apoptosis ratio of cardiomyocyte went up again with the time of
      constriction after surgery. TUNEL method revealed that positive nuclei were
      observed in cardiomyocytes exclusively in the left ventricle; the apoptosis ratio
      increased when constriction continued. TUNEL method confirmed the result of FCM.
      These data indicate that cardiac hypertrophy is initiated by apoptosis of
      cardiomyocyte, these two factors(hypertrophy and apoptosis) maintain the balance
      between growth and death during the early short period of aortic constriction,
      and when aortic constriction goes on they are involved in the pathogenesis of
      heart remodeling.

PMID- 11450538
TI  - [Effects of the alterations of membrane shear elastic modulus and viscosity on
      the deformation and orientation of RBCs].
AB  - Neuraminidase can partly remove the surface charge of RBCs through a biochemical
      interaction; thus it can give rise to alterations in the microstructure of
      membrane, the shear elastic modulus (E) and the viscosity(micron) of membrane.
      Changing the time of treatment and the dose of neuraminidase and using a new
      ektacytometry that can separate deformation index DI into orientation index
      (DI)or and small deformation index (DI)d for RBCs in shear flow field of low
      viscosity, we measured (DI)d and the half time t0.5 when the DI recovered to half
      of the maximum in the process of relaxation for every treated sample. (DI)d and
      t0.5 were put respectively into the RBC membrane shear elastic modulus formula
      and the membrane viscosity formula which were put forward by Wen Zong-yao and Yan
      Zong-yi et al[1]. The rules of the alterations of E and micron were obtained. We
      also measured DI and (DI)or. It was found that E and micron increased greatly but
      DI and (DI)or decreased when the dose of neuraminidase and the time of treatment
      were increased. There was a contrary correlation between them. These data
      demonstrated that the increase of E and micron weakened the deformability and the
      ability of orientation of RBCs.

PMID- 11450539
TI  - [The cytotoxic effects of the adriamycin magnetic albumin microspheres combined
      with external magnetic fields on the malignant tumor cells].
AB  - This study sought to assess the inhibitory effects of the adriamycin magnetic
      albumin microspheres (ADM-MAMs) on Walker-256 malignant tumor cells in vitro
      induced by the permanent magnetic fields. The cultured Walker-256 cells were
      divided into three groups; the group of ADM-MAMs combined with magnetic fields,
      the group of AMD-MAMs without magnetic fields, and ADM group. The growth states
      of the cells were observed and photographed under the inverted microscope. The
      inhibitory rates(IR) were assayed by the modified MTT colorimetric method. The
      results showed that the IR of the ADM-MAMs group were similar to those of the ADM
      group (P > 0.05), but the group of ADM-MAMs combined with magnetic fields had
      obviously higher IR and significant changes of the cells' shapes. These findings
      indicate that the anticancer effect of ADM-MAMs on malignant tumor cells is
      similar to that of ADM, and such effect can be increased by the combined use of
      ADM-MAMs and external magnetic fields.

PMID- 11450540
TI  - [A biomechanical model of human knee-joint elastic articulate contact].
AB  - In this paper, based on the characterizations of human knee-joint anatomical
      structures and reports of the literature and experiments, a biomechanical model
      of the human knee-joint elastic articulate contact is developed under the
      conditions of sampling the human knee-joints. This model is believed to be a
      powerful tool for functional analysis of the knee, for evaluation of surgical and
      diagnostic procedures and for design of artificial joints.

PMID- 11450541
TI  - [The development of multi-lead EEG telemetry and tele-monitoring system].
AB  - This paper introduces a kind of EEG Telemetry and Tele-monitoring system. With
      the use of the public telephone network to transport signals and the portable EEG
      recording system as the sender of system, the EEG data of 20 standard leads can
      be transmitted to the receiver of system (monitoring center) synchronously. And
      at the monitoring center, the waves can be displayed real-time, freezing, stored,
      reviewed, analyzed and printed, thus providing aid in remote diagnosis and
      treatment consultations.

PMID- 11450542
TI  - [Fast SEP measurement applied to intraoperative spinal cord monitoring].
AB  - Spinal cord monitoring techniques based on measuring somatosensory evoked
      potential (SEP) are presented. The principles and the experimental system for
      spinal cord monitoring are described in detail in the paper. The fast SEP
      measurement algorithm using pseudo-random sequence technique is also given.
      Experimental results show that our techniques can greatly improve the monitoring
      as compared to the traditional method, and further research in this connection is
      worth doing.

PMID- 11450543
TI  - [Study of continuous wavelet transform on detecting and enhancing blood vessel in
      DSA image].
AB  - Low contrast is the shortcoming of the image in Digital Subtraction Angiography.
      This paper presents a new approach for the enhancement of blood volume in DSA
      image. The wavelet transform was applied to detect blood edges, and then the
      image contrast was enhanced by the method of contrast stretched. Because the
      continuous wavelet adopted in this study can detect gray variety in different
      orientations, the blood vessel edge detected by this algorithm is more precise
      and complete. Moreover, because the module of image noise by wavelet transform is
      smaller, the algorithm can protrude blood vessel but restrain noise in
      background. The processing result showed a very good optical effect of 3
      dimensional objects for medical diagnoses.

PMID- 11450544
TI  - [Auto-detection of contour in echocardiographic images based on active contour
      model].
AB  - Contour detection is one of the most difficult problems in the multi-dimensional
      reconstruction of echocardiographic images. A method based on active contour
      model is presented in the present paper to solve this problem. First, according
      to the characteristic of the ultrasonic medical images, an adaptive weighted
      median filter is used to suppress speckle noise and an adaptive threshold value
      is selected to get binary image. Then, mathematical morphological treatment is
      utilized to get the initial contour. At last, active contour model is employed to
      revise the initial contour and get the accurate final contour. Experiments with
      real and interpolated ultrasonic images are presented. The results show the
      effectiveness of this method. This method has practical use in the multi
      dimensional reconstruction of ultrasonic medical images.

PMID- 11450545
TI  - [The vectorial algorithm for articulate motion of human entities].
AB  - The human moving system is defined as a rigid frame, which contains 19 articulate
      entities. Entity rotates around the father node and its son node is the father of
      another entity at the next level. The human frame is divided into 5 entity links.
      Through the vector summation algorithm and along the link, each entity's father
      nodes are calculated successively, and the vectorial frame of human posture is
      constructed. With all the entity patterns pasted on the vectorial frame, the
      picture of human moving posture is drawn.

PMID- 11450546
TI  - [3D visualization and information interaction in biomedical applications].
AB  - 3D visualization and virtual reality are important trend in the development of
      modern science and technology, and as well in the studies on biomedical
      engineering. This paper presents a computer procedure developed for 3D
      visualization in biomedical applications. The biomedical models are constructed
      in slice sequences based on polygon cells and information interaction is realized
      on the basis of OpenGL selection mode in particular consideration of the
      specialties in this field such as irregularity in geometry and complexity in
      material etc. The software developed has functions of 3D model construction and
      visualization, real-time modeling transformation, information interaction and so
      on. It could serve as useful platform for 3D visualization in biomedical
      engineering research.

PMID- 11450547
TI  - [The quantitative analysis of voice disease based on fractal method].
AB  - The fractal method is employed to check the voice diseases. The severity of
      pathological changes of human voice can be analyzed objectively and
      quantitatively with different fractal dimensions. With this method we can end up
      the history of judging the voice with subjective hearing and it is of great
      importance to the development of laryngology.

PMID- 11450548
TI  - [Study of EEG processing system and EEG wavelet transform].
AB  - In this paper are reported our studies on the time and frequency characteristics
      of wavelet transform, the EEG signals processing through wavelet transform, the
      EEG analysis and reconstruction results. The related EEG processing system design
      and implementation are given in detail. This system may be applied to EEG
      feedback research and EEG monitoring.

PMID- 11450549
TI  - [Study on the noninvasive measurement of cerebral oxygen saturation and cerebral
      phronetal function].
AB  - With the use of Near-infrared spectroscopy(NIRS), the noninvasive measurement of
      cerebral oxygen concentration can be achieved in vivo based on the Lambert-Beer
      Law. In this paper, we discuss the possibility of studying higher brain functions
      through a combination of cerebral oxygen saturation and cerebral function
      measurement. Event-related experiments are introduced to measure the cerebral
      phronetal function. Time domain curves show sight differences among these
      experiment results. However, with the aid of DFT, experiment data of all five
      human volunteers show that the frequency near 20 Hz or 40 Hz is evoked depending
      on the difficulty of the mental tasks. The results demonstrate the feasibility of
      cerebral function studies by means of cerebral oxygen saturation measurement
      analysis in the frequency domain.

PMID- 11450550
TI  - [MEG inverse solution using Gauss-Newton algorithm modified by Moore-Penrose
      inversion].
AB  - In magnetoencephalogram(MEG) basic studies, it is an important issue to estimate
      magnetic source parameters by inverse solution. It is known that the magnetic
      field equations are nonlinear, thus explicit solutions are difficult to obtain.
      However optimization methods are available to this parameter estimation. In many
      usually used nonlinear local optimization algorithms, Gauss-Newton's is of fast
      convergent speed. When this algorithm is used, the singularity of the Jacobien
      matrix about the minimum least square error must be considered carefully. If the
      matrix is singular, the equation for searching direction has no general solution.
      One way to overcome this problem is to use negative gradient as searching
      direction, but it may cause descent of convergent speed. Another way is known as
      Levenberg-Marquardt algorithm which makes the matrix non-singular by adding some
      improved factors to it. In this paper we utilize Moore-Penrose inversion for the
      solution of iterative searching direction equation. In appendix we demonstrate
      that the searching direction obtained by the proposed method is successful.
      Computer simulation also demonstrates that by reasonable selection of initial
      iterative values, the modified Gauss-Newton algorithm is effective for MEG
      inverse solution in the case with one or two source dipoles.

PMID- 11450551
TI  - [RGD peptides and endothelialization of biomaterials].
AB  - Endothelialization can remarkably improve blood compatibility of biomaterials and
      promote their clinical application, especially the uses of cardiovascular grafts.
      The attachment and growth of endothelial cells on artificial surfaces is the
      critical factor affecting the process of endothelialization. Many adhesive
      proteins contain the Arg-Gly-Asp(RGD) sequence which plays an important role in
      cell adhesion, migration and growth. In this review, the interaction of RGD
      peptides sequence and integrins, the influential factors of RGD peptides
      bioactivity and its application in endothelialization of biomaterials were
      discussed.

PMID- 11450552
TI  - [Recent developments of magnetic microspheres for use in the fields of
      biomedicine].
AB  - This paper presents a review of the recent developments of magnetic microspheres
      (MMS), a new kind of multi-function reagent for uses in the fields of cytology,
      immunology, microbiology, molecular biology, clinical diagnosis and treatment,
      etc.

PMID- 11450553
TI  - [Using self-assembled monolayers to understand the interactions of surfaces with
      cells].
AB  - It is important to understand the interactions of surfaces with cells. Self
      assembled monolayers formed on the adsorption of long-chain alkanethiols to the
      surface of gold or alkylsilanes to hydroxylated surfaces and their patterned
      surfaces permit of understanding and controlling over the surface-cell
      interactions at the molecular scale. The present paper reviewed the latest
      research in using patterned self-assembled monolayers to understand surface-cell
      interactions.

PMID- 11450554
TI  - [Application of poly-amino-acid in drug controlled release systems].
AB  - Poly-amino-acid is one of the polymers with good biocompatibility. It has a
      special use in the field of controlled release drug. In this article are reviewed
      the types, modification, dosage forms, structure and biocompatibility of poly
      amino-acid.

PMID- 11450555
TI  - [Preparation and application of polylactide].
AB  - Polylactide and its copolymers are polymer materials that can be degraded by
      organisms and have good biocompatibility. Since the polymer materials have no
      toxicity and can be absorbed, greater and greater attention has been paid to the
      related researches and development, and they are increasingly applied in various
      areas, especially medicine and pharmacy. There are three methods for preparing
      polylactide and its copolymers. The tests for evaluating the degraded property of
      polylactide and its copolymers have been existing for more than thirty years, but
      all of them have their defects. The property and technological level of
      polylactide and its copolymers remain to be improved for use in some areas. Once
      the manufacture of poly lactide is industrialized, it can be of wide application
      in the fields of medicine and degraded plastics.

PMID- 11450556
TI  - [Finite element analysis of spine biomechanics].
AB  - In this paper is summarized and classified the recent great progress in the
      research of spine biomechanics analysis. In addition, the relevant clinical
      significance as well as some possible research trends of finite element model
      establishment are also clarified. As a theoretical method, only by close links
      with clinical practice can finite element analysis really help explain the onset
      and development of diseases and forecast the curative effects.

PMID- 11450557
TI  - [The technical method for noninvasive magnetic stimulation of nerve center and
      its clinical application].
AB  - The increasing use of non-invasive magnetic stimulation technique for nerve
      center function examination and functional neuromuscular rehabilitation is a new
      cynosure in biomedical engineering and neuro-electrophysiologic researches. This
      paper analyzes theoretically the magnetic stimulation of first demonstration
      extending the technique model to human body, and the magnetic principle of
      physics. The characteristics of magnetic stimulation can be highlighted by
      comparing it to conventional electrical stimulation. Also presented are the
      peripheral multichannel magnetic stimulation to mimic electrical stimulation and
      the clinical functions toward neuromuscular rehabilitation.

PMID- 11450558
TI  - [Progress in studies on the mechanism of substance addiction in central nervous
      system].
AB  - The mechanism of substance addiction in the central nervous system is the key
      point to solve the problem of drug addiction in clinical prophylaxis and
      treatment, but it has been obscure so far. Previous researches in this field
      suggested that the higher brain function of the learning and memory might be
      pivotal in understanding the mechanism of substance addiction. It is the intent
      of this review to integrate and analyze the substance addiction and the learning
      and memory in an attempt to shed light on the strategies to conduct further
      studies in this field.

PMID- 11450559
TI  - [Advance of technology in the analysis of brain wave in patients with
      schizophrenia].
AB  - Recent advance of several leading technologies including EEG, EP and BEAM applied
      in the analysis of brain wave in schizophrenic patients was discussed in this
      paper. The perspectives for the application of these technologies and some
      opinions from the authors are also presented.

PMID- 11450560
TI  - [The computer-aided measurement of medullary canal in proximal femur].
AB  - This study was conducted to search the law of the parameters of medullary canal
      section shape in proximal femur. The methods of image-processing and taper-curve
      fit mathematics were adopted in the acquisition of data and parameters. Computer
      aided method and manual method were employed to measure 10 samples of section
      shape in proximal femur. The results showed that no significant difference was
      seen between the computer-aided method and manual method(P> 0.05). This approach
      could reduce man-made errors and process mass samples automatically by computer.

PMID- 11450561
TI  - [Tracing algorithms of ECG tracks from scanned image].
AB  - This paper presents a discussion on the tracing algorithms of the extraction of
      Electrocardiogram (ECG) data from scanned image of hardcopy ECG. We have advanced
      a new algorithm integrated by seek-and-predict method and polygon model method,
      which can tolerate crossing of two leads, fault-line and disturbing of grid
      lines. Two practical situations that may be encountered while processing hardcopy
      ECG are discussed in detail. Furthermore, the after-treatment of extraction
      filtering is considered and an SVD-based filter designed to smooth ECG signal is
      analyzed.

PMID- 11450562
TI  - [Application of computer image process to the research on the contact
      characteristics of subtalar joint].
AB  - With the use of computer image processing technology, a new method was proposed
      for studying the contact characteristics of the subtalar joint. The results
      showed the total subtalar articulation area was 9.52 +/- 0.40 cm2. On neutral
      position and under 600 N load, the contact area of the subtalar joint was 2.00 +/
      0.11 cm2. The contact area of the posterior articulation was significantly
      larger than that of the anterior and medial articulation (p < 0.01). The average
      contact pressure was 19.3 +/- 1.38 N, the force transmitted by the subtalar was
      389.16 +/- 28.75 N, which accounted for about 64.86% of the applied shank load
      (600 N), and 69.39% of the force was transmitted by the posterior articulation.
      The posterior articulation plays an important role in the load. The fracture line
      of the calcaneus often appears in this area.

PMID- 11450563
TI  - [A new algorithm for displaying the cutting isosurface of structures].
AB  - The existing algorithms for displaying the cutting isosurface of the structure
      are not suitable for interactive display because they spend too much time on
      calculation when a fair amount of data is submitted to processing. This paper
      presents a new algorithm for accelerating the cutting of structure by using the
      area partition and the increment calculation to reduce the unnecessary
      calculation in cutting the structure. It is suitable for real time interactive
      displaying, especially in the case of a vast amount of data.

PMID- 11450564
TI  - [Primary study on heart rate variability of non-linear dynamics in patients with
      coronary artery disease and diabetes].
AB  - This is a comparative study on the non-linear dynamics between 30 healthy
      controls and three groups of patients with single coronary artery disease(n =
      20), multi-coronary disease(n = 8), and diabetic patients with diabetic autonomic
      neuropathy (DAN)(n = 18), respectively. We selected and adopted six quantity
      indices of dispersed-dot plot, including the area of plot (SQ), long-axis (LA),
      short-axis (SA), the angle of long-axis and short-axis (ALS), vector length index
      (VLI) and vector angle index (VAI), and Kolmogorov entropy and fractal dimension.
      We found that the non-linear indices in healthy control had obvious day-to-night
      change, while the change in coronary artery disease patients decreased and
      disappeared in diabetics. By the findings that both coronary artery disease
      patients and diabetic patients had the turbulence of vegetal nerve system, we
      concluded that the vegetal nerve activity might be an important factor in heart
      non-linear dynamics. And marked differences in the non-linear indices were seen
      between the normal control, the single-vessel, multi-vessel coronary artery
      disease patients, and the diabetic patients, thus suggesting that these indices
      may be used in clinical practice.

PMID- 11450565
TI  - [Investigation on the mechanics of adhesion to the selective extracellular matrix
      coated surfaces of lung cancer cells].
AB  - The adhesion properties of tumor cells with extracellular matrix(ECM) are closely
      associated with their invasion and metastasis. Our work reported here was
      intended reveal the relevant biomechanical and biorheological manifestations of
      human lung cancer. Using micropipette aspiration technique, we investigated
      quantitatively the adhesive mechanics properties of high metastatic human giant
      cell carcinoma(PG) cells as well as low metastatic adenocarcinoma(PAa) cells of
      lung based on cell culture in vitro. The results showed that the adhesion forces
      of PAa and PG cells to collagen IV were significantly higher than those to glass
      surfaces, but at the lower concentrations(1.00 microgram/ml and 2.00
      micrograms/ml) of collagen IV, the amplitude for the increase of adhesion forces
      of PG cells were less than the amplitude for that of PAa cells, and most of the
      adhesion force values of PAa cells to the coated surfaces of incorporation of
      laminin along with 2 micrograms/ml collagen IV were significantly greater than
      those of PG cells. At the lower concentrations(0.625 microgram/ml for PAa cells,
      and 0.625 microgram/ml, 1.25 micrograms/ml for PG cells) of laminin tested, the
      adhesion force values of PAa and PG cells all decreased, but the amplitude and
      level for the decreased values of adhesion forces of PG cells were greater than
      those for the PAa cells. In conclusion, the adhesive and proteolytic behaviour of
      cancer cells to extracellular matrix might be mediated mainly by tumor cell
      membrane receptors such as integrin receptors and laminin receptors, it might
      affect the biological characteristics and the metastasis of the tumor cells. The
      results may benefit to explain some questions in biomechanical views about how
      the highly metastatic PG cells are prone to migration and invasion.

PMID- 11450566
TI  - [Experimental studies on muscle fatigue of human limb motion with FNS].
AB  - The basic characteristic of the functional neuromuscular stimulation signals
      suitable to body is preliminarily determined after the fatigue performance of the
      biceps, and the physiological reaction to stimulation is investigated using many
      continuous stimulation signal patterns. The flexion motion of the elbow joint
      (right hand) of a healthy man was taken as our research objective. The surface
      electrodes were connected to the biceps and a micro angle sensor was mounted on
      the elbow joint (right hand). The curves of angular displacement for the elbow
      joint motion were obtained by using functional neuromuscular stimulation (FNS)
      limbs motion measurement instruments. The results demonstrate that the biceps are
      characterized by the non-linear and time-variant no matter what the stimulation
      patterns are, that continuous slow stimulation signals can reduce the muscle
      fatigue of the biceps, and that the stimulation frequencies ranging from 30 Hz to
      50 Hz are applicable to the neuromuscular system.

PMID- 11450567
TI  - [The use of limit amplitude technique in clinical cardiac electrical signal
      recording].
AB  - Based on the electrophysiologic mechanism of cardiac electrical action and the
      theory of voltage effect, the limit amplitude technique was employed to obtain
      the best clinical record effects. The results showed that limiter could limit the
      oversize signals overlapping each other and make the tiny signals magnification
      without distortion, such as the His bundle deflection in His Bundel Electrogram.
      At the same time, all signals recorded at multichannel physiologic recorder were
      clear and did not interfere with each other. Furthermore, the limiter not only
      improved the recording quality but also protected the cardiac electronic
      equipment because overdue stimulation signal was limited at a given electronic
      level during the recording of transesophageal pacing.

PMID- 11450568
TI  - [Studies of a new adsorbent cross-linked agar beads entrapped attapulgite clay
      for hemoperfusion].
AB  - The preparation and properties of a new adsorbent cross-linked agar beads
      entrapped attapulgite clay (CAA) are reported in detail. Medicinal attapulgite
      clay made in China was encapsulated with agar, shaped in organic solvent, and
      cross-linked by epichlorohydrin. The products withstood autoclaving at 121
      degrees C for half an hour with no breakage, and had a good selective adsorption
      ability for some model compounds and medicaments such as methylene blue and
      phenothiazine drugs. Preliminary investigations and SEM photographs indicate that
      the CAA as an adsorbent is relatively hemocompatible for hemoperfusion.

PMID- 11450569
TI  - How will HIPAA affect hospital Web sites?

PMID- 11450571
TI  - The debate over HIPAA's likely implementation cost.

PMID- 11450572
TI  - CareGroup site takes some of the administrative hassle out of healthcare.

PMID- 11450574
TI  - Children's Hospital of Philadelphia to phase in wireless Web.

PMID- 11450575
TI  - WellSpan Health to pilot eCRM (customer relationship management) application.

PMID- 11450576
TI  - Hospital group creates sustainable benchmarking initiative.

PMID- 11450577
TI  - VHA ventures into benchmarking of clinical trials for consumers.
AB  - The hospital association has partnered with Vital Medicine to provide consumers
      and physicians a comprehensive source of information about clinical trials.
      Primary funding is from pharmaceutical companies and other clinical trial
      sponsors.

PMID- 11450578
TI  - Software aims to speed up dissemination of guidelines.
AB  - Software being developed by a Duke researcher aims to cut time needed for
      dissemination of new guidelines. The strategy is painless conversion of clunky
      text-based guidelines to linear algorithms.

PMID- 11450579
TI  - Researchers test system to custom-tailor guidelines.
AB  - Do you ever want to adapt standard guidelines to fit the demographic and clinical
      characteristics of particular patient population? It'll be possible sooner than
      you think.

PMID- 11450580
TI  - Nurses quick to adopt handheld computers.
AB  - The payoff is a dramatic decline in the drudgery of paperwork. Here's an example
      from home health nursing.

PMID- 11450581
TI  - Georgia software firm integrates physician management tools.
AB  - Single program provides practice management, human resources, and even medical
      records applications.

PMID- 11450582
TI  - [Physicians, internet and new knowledge. Utilization and efficiency of new
      continuing education media in the hospital].
AB  - BACKGROUND AND OBJECTIVES: The application of new information technologies will
      have a lasting impact on the physicians' working environment. Not only will
      classic learning methods change, but also ways of communication and strategies to
      find relevant information. This survey is designed to demonstrate current methods
      of and demand for continuing medical education and communication. METHODS: 110
      participating physicians (26% female, 74% male) in nine different regional
      hospitals were asked regarding "continuing medical education", "communication"
      and "use of computerized technology". RESULTS: Most physicians regard their
      colleagues, scientific journals, textbooks and scientific meetings as most
      useful. The internet, scientific staff at research institutions and
      pharmaceutical representatives were valued as less useful. Physicians regarded
      scientific basis, speed and user-friendliness as the most important features of
      potential data and knowledge sources. Case specificity, German language and
      interactivity were viewed as less important. Most physicians expressed a growing
      need for education regarding use of e-mail as a communication tool and internet
      research techniques. CONCLUSION: Continuing medical education is in strong
      demand. The successful introduction of modern information technologies into
      physicians' daily work may and should be enhanced by specifically tailored
      training courses.

PMID- 11450583
TI  - [A new paracentesis needle for ascites and pleural effusion compared with the
      venous indwelling catheter. A prospective, randomized study].
AB  - BACKGROUND: Diagnostic or therapeutic paracentesis of ascites or pleural
      effusions is part of the daily routine on many hospital wards and in outpatient
      clinics. In Germany, paracentesis is usually performed with angiocaths. However,
      the therapeutic large volume paracentesis of ascites and paracentesis of pleural
      effusions with angiocaths is often cumbersome and quite often paracentesis fails,
      forcing the physician to repuncture. This is mainly due to the fact that
      angiocaths are not designed for such interventions. PATIENTS AND METHOD: 45
      patients with ascites or pleural effusions were treated with a new needle
      specially designed for paracentesis, or with an angiocath. The new paracentesis
      needle was compared with the angiocath needle under the following aspects:
      necessity and number of positional corrections of the needle, necessity of and
      reasons for repuncture, duration of puncture, flow capacity, subjective
      practicability of paracentesis and patient acceptance of the paracentesis needle.
      RESULTS: The paracentesis needle was superior to the angiocath in all
      investigated respects. Significantly, the paracentesis needle had a much higher
      success rate in the complete drainage than had the angiocath. CONCLUSION: The
      paracentesis needle was objectively superior as compared to the angiocath. It
      might help to avoid additional complications due to repuncture and it will
      increase the patients' comfort.

PMID- 11450584
TI  - ["Epidemiology" of the value of orally administered morphine as therapy of severe
      pulmonary emphysema of the pink-puffer type].
AB  - OBJECTIVES: Patients with severe emphysema from pink puffer type (PPT) are
      symptom-limited due to dyspnea even at low level of activity. In this study we
      investigated the clinical effect of oral morphine in this group of patients.
      MATERIALS AND METHODS: Based on the analysis of medical records (n = 456
      patients) and a currently answered questionnaire (n = 205 patients) we analyzed
      data of all patients with emphysema being treated from 1995-1999. RESULTS:
      Dyspnea improved during the adaptation period on the ward in 59.4% of the whole
      population being treated with morphine and in 67.7% of the analyzed patients
      after discharge. Before discharge the treatment with morphine was finished by
      38.9% of the population. In the group of long-term survivors approximately 50% of
      patients continued the treatment. In total, about 10% of the collective finished
      the treatment due to intolerable side effects. In the 5-year observation period
      morphine has been increasingly applied in an earlier stage of the disease.
      CONCLUSION: In patients with severe emphysema from pink puffer type a trial with
      morphine is justified. In particular the beneficial effect on dyspnea in the
      responder group and the acceptable rate of side effects underline this strategy.

PMID- 11450585
TI  - [Antiphospholipid syndrome. Pathogenesis, molecular basis and clinical aspects].
AB  - BACKGROUND: In 1983 the antiphospholipid syndrome was first described as an
      independent clinical entity by Graham Hughes and characterized by thrombosis,
      thrombocytopenia and recurrent fetal losses. In the following years evidence
      accumulated from various studies that the thrombotic events in the
      antiphospholipid syndrome correlate with elevated serum titers of
      antiphospholipid antibodies. These autoantibodies represent a very heterogeneous
      group as multiple specificities against various negatively charged phospholipids
      are found. Most commonly described are antibodies against cardiolipin, but also
      cross-reactivities between the different phospholipids are observed. Moreover,
      efficient binding of antiphospholipid antibodies against a phospholipid requires
      the presence of certain protein-cofactors which on the other hand can be antigens
      themselves. PATHOGENESIS: Although numerous animal models strongly indicate that
      antiphospholipid antibodies play a causal role in the pathogenesis of the
      disease, the exact pathogenetic mechanisms are still to be elucidated. There is
      accumulating evidence from in vitro studies with poly- and monoclonal
      antiphospholipid antibodies that these autoantibodies are able to interfere with
      all aspects of the hemostatic balance. Influences of antiphospholipid antibodies
      on plasmatic processes of the coagulation cascade as well as antithrombotic and
      fibrinolytic mechanisms are described. Furthermore, antiphospholipid antibodies
      are able to exert prothrombotic effects on cells participating in hemostasis,
      mainly platelets and endothelial cells. THERAPEUTIC APPROACHES: Therapeutic
      approaches to the antiphospholipid syndrome today are mainly restricted to the
      prevention of further thrombosis by permanent anticoagulation. Although 30-50% of
      all patients, according to the literature, with moderately to highly elevated
      antiphospholipid antibody titers develop the clinical symptoms of the syndrome,
      there are only few studies investigating the benefits of a prophylactic
      anticoagulation of the affected patients. There is an urgent need for prospective
      clinical studies to clarify this question. Therapy of nonthrombotic
      manifestations of the antiphospholipid syndrome are scarcely standardized. In
      obstetrics, treatment with aspirin, heparin and steroids is the main approach.
      Here also controlled studies are restricted to small numbers of patients and are
      therefore of limited validity.

PMID- 11450586
TI  - [Thrombotic-thrombocytopenic purpura (Moschcowitz syndrome)].
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), in 1924 first described by
      Moschcowitz, is a clinically heterogeneous syndrome associated with
      thrombocytopenia, Coombs-negative hemolytic anemia, neurologic changes, renal
      impairment, and fever. TTP is found after various bacterial or viral infectious
      diseases, autoimmune diseases and also in association with different drugs.
      PATHOGENESIS: After initial endothelial cell injury unusually large von
      Willebrand factors (vWF) are found in plasma of patients with thrombotic
      thrombocytopenic purpura. Because of impaired proteolysis these large forms lead
      to thrombosis of the small vessels. The microangiopathy is followed by mechanical
      destruction of red cells. In peripheral blood smears these fragmentocytes are
      important for diagnosis and clinical course. THERAPY: The therapy of choice is
      plasma exchange against fresh frozen plasma, whereupon the mortality could be
      dramatically reduced in the past decades. In case of treatment resistance to
      plasma exchange there exists no common treatment schedule. One therapy option is
      immunosuppressive treatment with corticosteroids and vincristine. In case of
      chronic relapsing TTP splenectomy should be discussed. In spite of severe
      thrombocytopenia substitution of thrombocytes is contraindicated.

PMID- 11450587
TI  - [Ruptured splenic artery aneurysm--a rare cause of recurrent gastrointestinal
      hemorrhages].
AB  - HISTORY AND CLINICAL FINDINGS: A 51-year-old asthenic patient attended the
      hospital with syncope, head injury, tarry stool and severe anemia. There was a
      history of alcohol and nicotine abuse, but no known preceding diseases of the
      liver or gastrointestinal tract. Except hypotension, examination of the patient
      did not show any further abnormalities. DIAGNOSTIC PROCEDURE: An upper and lower
      endoscopy did not show any evidence of a bleeding source although the stomach was
      full of hematin. An abdominal ultrasound demonstrated signs of a chronic
      pancreatitis and a big cystic structure in the area of the pancreatic tail.
      Pulsed and color Doppler imaging followed by angiography led to the diagnosis of
      a pseudoaneurysm of the splenic artery. TREATMENT AND COURSE: After confirming
      the diagnosis, a laparotomy was performed. It revealed a pseudoaneurysm arising
      from the splenic artery that had penetrated the stomach and caused bleeding.
      Resection of the aneurysm, the stomach fundus, the left pancreas and the spleen
      was performed. 10 days after laparotomy, the patient was discharged from hospital
      in a good clinical condition. CONCLUSION: Pseudoaneurysms of the splenic artery
      are an uncommon cause of gastrointestinal bleeding. The most important factor in
      detecting a pseudoaneurysm is considering the diagnosis. It is necessary to check
      for a pseudoaneurysm secondary to pancreatitis with pulsed or color Doppler
      imaging especially if a pseudocyst was first diagnosed with abdominal ultrasound.
      Because of the high mortality of a pseudoaneurysm, surgical resection or
      interventional radiology should be done as early as possible.

PMID- 11450588
TI  - [Neck swelling as the major symptom of lymph node and intestinal tuberculosis].
AB  - BACKGROUND: Gut tuberculosis appears to be a rare diagnosis in Central Europe.
      The main diagnostic method is endoscopy with biopsy in order to win histology and
      a culture. By means of endoscopy the differential diagnosis to Crohn's disease is
      sometimes difficult. Computertomography and/or ultrasound can facilitate the
      diagnosis of gut tuberculosis. CASE REPORT: A 64-year-old woman presented in our
      hospital with cervical lymph nodes and ulcerations in the cecum and near the
      ileocecal valve. Major symptoms were abdominal pain, loss of weight, diarrhea and
      febrile temperature. Histology and culture revealed tuberculosis. The common
      antituberculotic therapy had to be stopped due to severe allergic reaction. After
      desensitization the patient could be treated successfully with a triple
      antituberculotic therapy without further complication. CONCLUSION: Beside the
      early treatment with tuberculotic drugs it is very important to consider the
      differentiation of a gut tuberculosis.

PMID- 11450589
TI  - [Fatal sinus vein thrombosis in a patient with mixed connective tissue disease
      and secondary antiphospholipid antibody syndrome].
AB  - BACKGROUND: The antiphospholipid (Huges) syndrome is a complication of connective
      tissue diseases characterized by thromboembolic occlusions of arterial and venous
      blood vessels. CASE REPORT: At the age of 13, the patient developed connective
      tissue disease with arthritis and myositis. The course of her disease was
      characterized by frequent relapses despite immunosuppressive treatment. She
      developed deep venous thrombosis of her right leg as a manifestation of secondary
      antiphospholipid antibody syndrome at the age of 15 and was subsequently started
      on oral anticoagulation therapy. Approximately 10 months later, however, she
      decided to try alternative medicine and stopped both anticoagulation and
      immunosuppressive therapy. Only after 4 weeks she developed seizures followed by
      respiratory arrest with the need for cardiopulmonary resuscitation. Despite
      intensive care she died 2 days later with the signs of severe cerebral edema
      causing herniation of the brainstem. Autopsy confirmed the diagnosis of severe
      edema of the brain as a result of extensive thrombosis of all sinus veins.
      CONCLUSION: A complete sinus vein thrombosis is a rare manifestation of
      antiphospholipid antibody syndrome. The lethal thrombosis in this case occurred
      during a period of reactive hypercoagulability after termination of
      immunosuppressive and/or anticoagulation therapy. This case report underlines the
      need for long-term anticoagulation in patients with the antiphospholipid
      syndrome.

PMID- 11450590
TI  - [Artificial respiration dependent respiratory failure in a 20-year-old patient.
      Heroin-induced capillary leak syndrome].

PMID- 11450591
TI  - Cost-effectiveness analysis of dialysis and kidney transplants in Japan.
AB  - Although kidney transplantation is considered to be more desirable than dialysis
      in terms of cost-effectiveness and patients' quality of life, there have been
      very few cases of kidney transplants in Japan. This study was conducted to
      compare the cost-effectiveness of dialysis and kidney transplants using
      Disability-Adjusted Life Years (DALYs) as an indicator of effectiveness. Most
      data necessary for the DALYs analysis were obtained from publications. The
      disability weights for dialysis patients and kidney transplant patients were
      estimated based on a questionnaire e-mailed to medical officials of the Japanese
      Government. Expected duration of treatment was estimated from the survival rates
      of dialysis patients and the graft-survival rates of transplant patients using
      the Weibull model method. The cost of dialysis and living-related donor (LRD)
      transplant included only medical expenditures and neglected all other costs, and
      the cost of cadaveric donor (CAD) transplant included the budget for organ
      procurement and distribution in addition to medical expenditures. The analysis
      showed that dialysis averted 138,019 DALYs/year, living-related donor transplant
      averted 5,740 DALYs/year, and CAD transplant averted 1,892 DALYs/year. The cost
      effectiveness ratio (C-E ratio) was 9,546 thousand yen/DALY for dialysis, 1,809
      thousand yen/DALY for LRD transplant, and 2,322 thousand yen/DALY for CAD
      transplant. These results could be used for the decision making of the Government
      on what resources should be allocated to the promotion of kidney transplantation.
      Also, the methodology used in this study can be applied to cost-effectiveness
      analysis of other organ transplants.

PMID- 11450592
TI  - A case of generalized Hailey-Hailey disease with fatal liver injury.
AB  - We report a case of a 59-year-old man with a severe generalized form of Hailey
      Hailey disease that was complicated by fatal liver injury. Erosive lesions were
      first noted in the axillary and perianal regions at 15 year of age, and Hailey
      Hailey disease was diagnosed based on the clinical features and histologic
      findings in skin biopsy specimens. The patient was treated with at first topical
      steroids and later a low dose of a corticosteroid, but the skin lesions gradually
      became generalized. At 45 years of age liver dysfunction was detected after
      azathioprine and vinblastine treatment for the generalized skin lesions. The
      liver injury gradually progressed and finally the patient died. The gene
      responsible for Hailey-Hailey disease was recently identified as ATP2C1, and it
      encodes a Ca(2+)-transport ATPase with broad expression, including in skin and
      liver. This finding suggests that mutation of the ATP2C1 gene may give rise to an
      extracutaneous phenotype, such as the liver dysfunction observed in severe cases,
      including our own. Further accumulation of cases is necessary to determine
      whether this is true.

PMID- 11450593
TI  - Reversibility of hepatic fibrosis: from the first report of collagenase in the
      liver to the possibility of gene therapy for recovery.
AB  - Since the authors reported the presence of collagenase in the liver as well as
      its increased activity in the early stage of hepatic fibrosis and its reduced
      activity in advanced fibrosis in rats induced by chronic CCl4 intoxication, in
      baboons fed alcohol chronically and in patients with alcoholic fibrosis, other
      investigators have demonstrated the same tendency of collagenase activity
      biologically and histochemically. Very recently, the authors demonstrated
      definite gene expression of collagenase during the recovery from experimental
      hepatic fibrosis using Northern blotting and in situ hybridization. The findings
      of in situ hybridization not only demonstrated the cells expressing collagenase,
      but also suggested much information on the mechanism of the recovery from
      fibrosis. Hepatic stellate cells play a key role not only in fibrogenesis but
      also in fibrolysis. The authors' recent observation revealed that collagenase
      (matrix metalloproteinase-13 (MMP-13)) gene expression appears very early in the
      process of recovery from liver fibrosis, and that both stellate cells and
      hepatocytes express MMP-13. Recovery from liver cirrhosis requires the gene
      expression of collagenase, increased production of the collagenase enzyme, and
      activation of the enzyme balanced with the specific inhibitors of collagenase.
      The understanding of molecular mechanisms of MMP-1 gene expression which is under
      investigation in our laboratory may provide us a new strategy for the treatment
      of liver fibrosis including the possibility of gene therapy.

PMID- 11450594
TI  - Professor Toshio Ito: a clairvoyant in pericyte biology.
AB  - Ito cells are liver-specific pericytes which were first described as Fett
      Speicherung Zellen, the fat-storing cells encircling outside sinusoidal
      endothelial cells, in 1951 by the late professor Toshio Ito. His pioneering
      approaches for morphological characterization of the cells stimulate
      investigators to further examine their functional roles in liver homeostasis: a
      body of evidence has been accumulated in recent years showing that the cells play
      a crucial role in storage and delivery of vitamin A, regulation of sinusoidal
      tone and local blood supply, and tissue repair and fibrosis. It is now widely
      accepted that microvascular pericytes including Ito cells serve as a key player
      that controls angiogenesis. Furthermore, recent studies support a concept that
      Ito cells constitutes a bridging apparatus mediating bidirectional metabolic
      interactions between sinusoids and hepatocytes, utilizing prostanoids and/or
      gaseous mediators such as nitric oxide and carbon monoxide as signaling
      molecules. This article reviews researches on this liver-specific pericyte and
      its leading roles in recent development of pericyte biology.

PMID- 11450595
TI  - A brief review of Dr F Gotoh's contribution to neuroscience: research in the
      field of cerebral blood flow and stroke.
AB  - Professor Emeritus Fumio Gotoh began and continues his remarkable career in
      medicine at Keio University. Since his graduation from medical school there in
      1951, Dr. Gotoh has devoted himself to neurology, especially in the enigmatic
      field of stroke science. He is most renown for his groundbreaking research and
      leadership in the study of cerebral blood flow and metabolism. Beginning with his
      doctoral thesis paper in 1959 entitled "Effects of blood pressure on cerebral
      circulation," our article briefly delineates how Prof. Gotoh has paved the path
      for current and future discoveries in modern medicine. Although wholly difficult
      to sum up Dr. Gotoh's extensive career in such a short article, we have attempted
      to chronologically list and furthermore to describe his numerous works. Herein we
      describe his expansion to the international arena with his contributions at Wayne
      State University as well as his novel cerebral blood gas monitoring techniques
      now used in modified fashion throughout the world. From his CO2-based
      investigations in animals to his study of the autonomic nervous system's role in
      human cerebrovascular control, we remark on Dr. Gotoh's accomplishments without
      the use of functional imaging. Yet despite the basic science theme of his
      research, he has always kept them clinically correlated to entities such as
      Cheyne-Stokes phenomenon and Shy-Drager syndrome. Prof. Gotoh has been asked to
      head some of the most influential stroke societies and was the second president
      of the International Stroke Society. In conjunction with leading authorities, he
      developed a quantifiable, evidence-based stroke scale which was introduced in the
      International Journal of Stroke in 2001. Today despite his retirement, Dr. Gotoh
      continues his work in cerebral blood flow and metabolism.

PMID- 11450596
TI  - Function of gonadotropin-releasing hormone in olfaction.
AB  - Gonadotropin-releasing hormone (GnRH) is present within neurons of the nervus
      terminalis, the zeroeth cranial nerve. In all vertebrate species, except in
      sharks where it is a separate nerve, the nervus terminalis consists of a chain of
      neurons embedded within olfactory or vomeronasal nerves in the nasal cavity. The
      function of the GnRH component of the nervus terminalis is thought to be
      neuromodulatory. Our research on GnRH effects on olfaction confirms this
      hypothesis. The processes of GnRH neural cell bodies located within chemosensory
      nerves project centrally into the ventral forebrain and peripherally into the
      lamina propria of the nasal chemosensory mucosa. GnRH receptors are expressed by
      chemosensory neurons as shown by RT-PCR/Southern blotting and GnRH agonist
      binding studies. Patch-clamp studies have shown that GnRH alters the responses of
      isolated chemosensory neurons to natural or electrophysiological stimulation
      through the modulation of voltage-gated and receptor-gated channels. Behavioral
      experiments demonstrate that interfering with the nasal GnRH system leads to
      deficits in mating behavior. These studies suggest that the function of the
      intranasal GnRH system is to modify olfactory information, perhaps at
      reproductively auspicious times. We speculate that the purpose of this altered
      olfactory sense is to make pheromones more detectable and salient.

PMID- 11450597
TI  - Melanoma antigens and their recognition by T cells.
AB  - During the last 10 years many melanoma antigens recognized by T cells have been
      molecularly characterized. This review summarizes the main features of these
      antigens, including both classes I and II HLA-restricted peptides, and describes
      their classification into diverse groups according to the tissue distribution of
      the antigens. The different in vitro and in vivo immunogenicity of such antigens
      is then discussed leading to the conclusion that Melan-A/MART-1 is the strongest
      among those tested being frequently recognized by patients' T cells both in vitro
      and in vivo. However, no correlation was found between T-cell response of
      melanoma patients to Melan-A/MART-1 and clinical response when it was used for
      vaccination. Data are also presented that suggest, through an ex vivo analysis
      carried out with tetramers staining of melanoma-specific T cells, that only in a
      limited number of advanced patients does a specific immune response develop. This
      response, however, appears unable to effectively counteract metastatic melanoma
      growth.

PMID- 11450598
TI  - Modern Japanese medical history and the European influence.
AB  - Before the first European visited Japan in 1549, traditional Chinese medicine was
      mainly employed in Japan. Francisco de Xavier, a missionary of the Society of
      Jesus, tried to promote the introduction of Christianity by providing a medical
      service for Japanese citizens. However, Japan implemented a national isolation
      policy in 1639 and cut off diplomatic relations with the rest of the world,
      except Holland and China. For over 200 years, until the American admiral Matthew
      Perry forced Japan to open its doors in 1853, Japan learned about western
      medicine only from doctors of the Dutch merchants' office or from Dutch medical
      books. After 1853, Western medicine was rapidly introduced into Japan, and great
      achievements by Japanese medical doctors soon followed, such as the serum therapy
      for tetanus, the discovery of the plague and dysentery bacilli, the invention of
      Salvarsan for the treatment of syphilis, and the demonstration of the
      neurosyphilis spirochete.

PMID- 11450599
TI  - [Sublingual immunotherapy with cat epithelial extract. Personal experience].
AB  - Because cats are a common pet in many houses and tourist complexes in the Canary
      Islands, sensitization to cat epithelium is a frequent problem. A total of 19.2%
      of patients with intrinsic asthma are sensitized to cat epithelium. In the Canary
      Islands, the percentage of sensitization among patients with a household cat is
      18.1%, which higher is higher than in the rest of Spain (11.9). Many patients
      with extrinsic asthma sensitized to house dust mites undergo conventional
      subcutaneous immunotherapy but evolution is unsatisfactory due to sensitization
      to cat epithelium (whether a cat is present or not). The aim of this study was to
      evaluate the clinical effectiveness of sublingual immunotherapy with extract of
      cat epithelium in monosensitized patients with perennial allergic rhinitis and/or
      bronchial asthma. Forty patients monosensitized to cat epithelium were selected.
      Of these, 20 were administered sublingual immunotherapy and another 20 received
      placebo. The following evaluation was carried out in both groups: in vivo and in
      vitro: symptom score, skin tests, nasal challenge with cat epithelium, specific
      IgE determination, specific IgG4 and eosinophilic cationic protein. After 1 year
      of treatment the cumulative dose was 3.6 micrograms of Fe ld I, equivalent to 10
      ng/drop. Duration of treatment was 365 days. Our conclusions, based on our
      patients in the Canary Islands, were the following: 1. Sublingual Fel d I therapy
      is effective after 1 year of treatment. 2. There were no modifications in IgE,
      eosinophilic cationic protein or skin tests. 3. An increase in IgG4 occurred
      which was related to clinical improvement. 4. In general, tolerance was good,
      except in one patient who presented urticaria and sublingual pruritus. 5. In
      polysensitized patients, sublingual immunotherapy to cat epithelium is
      complementary to immunotherapy to dermatophagoides.

PMID- 11450600
TI  - [Pain and gait problems in 3 (almost) adolescents with a dislocated hip].
AB  - Three young people, a boy aged 15 years and two girls aged 9 years and 13 years,
      had already suffered groin pain and knee pain for many months. They exhibited an
      antalgic walk, diminished function of the hip and radiographic signs of a slipped
      capital femoral epiphysis (SCFE). The complaints disappeared following in situ
      fixation with one or more screws. Epiphysiolysis of the caput femoris through the
      growth plate is a disorder of the growing hip. It is the most prevalent hip
      disease in adolescents. Obese boys are the most commonly affected. The aetiology
      is not known. The later SCFE is diagnosed and treated, the greater the chance of
      premature coxarthrosis. Avascular necrosis and chondrolysis are complications
      that can arise as a result of the operation.

PMID- 11450601
TI  - [Long-term intensive athletic training; few adverse effects on later physical
      health].
AB  - In general, physical activity benefits health. However, long-term intensive
      physical training may have detrimental effects on the health of some individuals.
      In cyclists, changes in the femoral arteries may occur leading to stenoses that
      are manifested in claudication type symptoms. Some endurance athletes may
      experience atrial fibrillations that are possibly related to long-term physical
      training. Older athletes only have an increased risk of osteoarthritis in joints
      that have suffered injuries. Menstrual disturbances and premature osteoporosis
      may occur in women as a consequence of intensive physical training. However, the
      risk for these adverse consequences of long-term physical training is small.

PMID- 11450602
TI  - [Ultrasound measurement of calcaneus: a promising method for prediction of
      osteoporotic fractures].
AB  - When carrying out quantitative ultrasound (QUS) measurements of the calcaneus,
      broadband ultrasound attenuation (BUA, in dB/MHz) and speed of sound (SOS, in
      m/s) are assessed. From in vitro studies it is known that the mechanical
      properties of trabecular bone (stiffness and strength) can be better predicted
      with QUS than with dual energy X-ray absorptiometry (DEXA). Bone mineral density
      (BMD) measurements with DEXA are currently used for the diagnosis of osteoporosis
      according to the WHO criteria. There is no consensus regarding the diagnosis of
      osteoporosis with QUS measurements of the calcaneus. In prospective studies in
      women of 65 years and older it has been shown that fracture risk assessment with
      QUS measurements is feasible. The value of QUS measurements for the follow-up of
      patients with skeletal disorders is not yet known. At present there are important
      differences between ultrasound devices and there is no standardisation. The
      development of quality standards for and cross-calibrations of QUS scanners is
      necessary, so that results from different devices can be compared. Although QUS
      of the calcaneus is a promising method for the prediction of osteoporotic
      fractures, its routine use in clinical practice cannot yet be recommended.

PMID- 11450603
TI  - [Roaming through methodology. XXXIV. Limitations of predictive models].
AB  - Predictive models can be readily used within the populations in which they were
      developed but they often give a less than satisfactory performance when applied
      to another population. The main cause of this poorer performance is the fact that
      predictive models are often developed and evaluated within one single population.
      In a lot of cases, the model includes too many predictors (or a small population
      is used), which increases the chance of overfitting. Both external and internal
      validation techniques have been developed to evaluate predictive models. The most
      stringent test is an external validation: the application of the model to a new
      population. The usability of a predictive model can be evaluated using the
      receiver operating characteristic (ROC) curve.

PMID- 11450604
TI  - [Diagnostic image (41). Molluscum contagiosum].
AB  - An 18-year-old woman presented with solitary molluscum contagiosum in the skin of
      the thorax.

PMID- 11450605
TI  - [General practitioner's workload: objective increase in 9 practices in Rotterdam
      and surroundings, 1992-1997 and an extrapolation to 2005].
AB  - OBJECTIVE: To assess the change in general practitioners' (GPs') workload during
      the period 1992-1997, calculated as consult frequency and GP-patient contact
      time, and to estimate the workload in 2005. DESIGN: Descriptive. METHOD: During
      the period 1992 to 1997, data from all GP-patient contacts from nine general
      practices in and around Rotterdam, the Netherlands, were registered and stored in
      a central database. The yearly GP-patient contact time in 1992 and 1997 was
      calculated using the measured contact frequencies and known figures from the
      medical literature on the distribution and average duration of the different
      contact types (consultation, home visit, telephonic consultation, other). The
      contact time in 2005 was estimated by extrapolating the contact time for the
      period 1992 to 1997, whilst bearing in mind the expected population composition
      in 2005. RESULTS: The number of GP consultations increased from 4.26 in 1992 to
      5.16 in 1997 (+21%). Compared with 1992, the yearly GP-patient contact time in
      1997 was at least 90 hours higher. Extrapolation to 2005, revealed a further
      increase in this contact time of 667 (+36%) hours compared to 1997. This
      predicted increase in the workload could mostly be attributed to an increase in
      the number of elderly patients and the number of contacts with these patients.
      CONCLUSION: The number of hours worked by GPs increased by 20% over a six year
      period and is expected to increase by about a third over the next few years.

PMID- 11450606
TI  - [HIV-positive drug users in South Limburg: number and characteristics, a capture
      recapture analysis].
AB  - OBJECTIVE: To estimate the number of HIV positive drug abusers (HDs) in South
      Limburg, the Netherlands, and to ascertain the characteristics of this group, so
      that special HIV healthcare can be planned. DESIGN: Capture-recapture analysis.
      METHOD: Capture-recapture analysis was carried out and abuser characteristics
      were determined using three incomplete, partially overlapping registers of HDs
      from the regional AIDS hospital, the Regional Institute for Addiction and the
      Municipal Health Service Centres in South Limburg. RESULTS: From the 80 HDs
      included, the Municipal Health Service Centres observed 59 HDs, the Institute for
      Addiction 45 and the hospital 44. The capture-recapture analysis gave an estimate
      of 110 HDs (95% CI: 91-164) in South Limburg. Assuming 1100 drug users in South
      Limburg of which 76% had injected on one or more occasions, the HIV prevalence
      among injecting drug users was estimated at 13% (110/836). From the observed HDs
      80% were male, with a mean age of 38 years (SD: 7) and a mean age at the onset of
      drug use of 18 years (SD: 5). All HDs currently injected or had previously
      injected. The first injected drugs were used at a mean age of 21 years (SD: 6).
      All HDs used heroine, 84% also used cocaine, 54% were homeless, 91% unemployed
      and 80% had a history of imprisonment. Further, 71% of the female HDs were
      prostitutes, 37% of the male ones visited prostitutes, 81% had contracted
      hepatitis B (of which 20% were a carrier) and all HDs were infected with
      hepatitis C. An estimate based on prevalence data gave 143/836 (17%) and that
      based on capture-recapture analysis with two registrations was 102/836 (12%).
      CONCLUSION: The number of HDs was estimated to be 110. The population had a
      marginalized existence and there was a risk of HIV spreading.

PMID- 11450607
TI  - [Endovascular treatment of 2 patients with an aneurysm of the descending thoracic
      aorta].
AB  - Two men, aged 71 and 70, who had previously experienced an abdominal aneurysm
      were found to have thoracic aortal aneurysms of respectively 8 cm and 7.5 cm in
      length. For the first patient an endovascular operation was carried out due to a
      high operative risk: with the help of a radiograph, four endoprostheses were
      inserted into the thoracic descending aorta via the femoral artery, after which
      the aorta diameter became more normal. A month later, the patient died from
      persistent renal failure, which had developed as a result of the previously
      ruptured abdominal aneurysm. In the second patient with an aneurysm of the
      proximal descending aorta, a left decompensation arose following aortal clamping
      during open surgical repair. Ten weeks later an endoprosthesis was inserted via
      the femoral artery. A year later the aortal diameter had decreased to 6.5 cm; the
      patient functioned well. The insertion of an endoprosthesis in the thoracic aorta
      is a minimally invasive procedure in which the patient experiences little
      perioperative inconvenience.

PMID- 11450608
TI  - [Pancreatitis ascribed to the use of itraconazole].
AB  - A 50-year-old woman was treated intermittently with itraconazole (Trisporal) due
      to onychomycosis. After the initial period of 7 days and after the first 9 days
      of the second period she experienced abdominal complaints. In the second episode,
      pancreatitis was diagnosed. No known risk factors for acute pancreatitis were
      present. The pancreatitis may have arisen due to the use of itraconazole. As far
      as we know, this side effect of itraconazole or other triazole derivatives has
      not previously been reported in the literature. It seems to be a rare side
      effect, for which the pathogenesis has yet to be elucidated.

PMID- 11450609
TI  - [Diagnosis in ulcerative disease: what is essential, what is unnecessary?].

PMID- 11450610
TI  - [Diarrhea: essential and rational diagnosis. Pathophysiological aspects and
      practical recommendations].

PMID- 11450611
TI  - [Constipation--essential and rational diagnosis].

PMID- 11450612
TI  - [Irritable bowel syndrome--what is possible and helpful in its diagnosis and
      treatment?].

PMID- 11450613
TI  - [Common forms of infectious diarrhea after trips abroad--what is proven and what
      is actually done?].

PMID- 11450614
TI  - [Is there any step-wise treatment of chronic inflammatory intestinal disease?].

PMID- 11450615
TI  - [Cytokine and anti-cytokine therapy in chronic inflammatory bowel diseases].

PMID- 11450616
TI  - [Follow-up control in chronic inflammatory bowel disease--complications, sequelae
      and cancer risk].

PMID- 11450617
TI  - [Definition and management of non-alcoholic steatohepatitis (NASH)].

PMID- 11450618
TI  - [PEG-interferons: significance for the treatment of viral hepatitis B and C].

PMID- 11450619
TI  - [Hepatic encephalopathy].

PMID- 11450620
TI  - [Ulcerative disease and dyspepsia--which treatment is proven?].

PMID- 11450621
TI  - [Advances in the ultrasonic diagnosis of liver diseases].

PMID- 11450622
TI  - [Ten-year trend of analgesic drug use (1984 to 1995): results of three MONICA
      based surveys in Augsburg)].
AB  - BACKGROUND AND OBJECTIVE: Use of drugs, especially analgesics, is thought to be
      responsible for the rising cost of the health system in Germany, but there are no
      published population data for analgesic intake in Germany. Data derived from the
      three MONICA surveys (Monitoring of Trends and Determinants of Cardiovascular
      Diseases) in Augsburg and its adjacent districts were analysed for the prevalence
      of analgesic usage between 1984 and 1995 (the first such survey for Germany).
      PATIENTS AND METHODS: A total of 5,899 males and 6,005 females (aged 25-64
      years), representative of the population, were selected and examined in 1984/85,
      1989/90 and 1994/95 (participation rate of those selected, 75-79%). Using a
      standardized protocol, all analgesic drugs taken during the previous 7 days were
      recorded and classified. The analysis was standardized for age and classified
      according to sex. RESULTS: Strong analgesics were not significantly used under
      the ambulatory conditions of this survey and were therefore excluded from the
      analysis. Intake prevalence of mild to moderately strong analgesics varied from
      5.9-8.9% in males and 9.9-13.4% in females. Prevalence was significantly at its
      lowest in 1989/90, but similar at the beginning and end of the 10-year period.
      Changes in prevalence of analgesic usage were similar to those of on-demand
      medication. Salicylic acid preparations containing higher dosages of the active
      ingredient were the drugs most commonly used, followed by aniline preparations,
      heteroaryl- as well as aryl-acetate and propionic acid derivates, pyrazole
      derivates, oxicam and anthranylic acid derivates. CONCLUSION: The prevalence of
      taking mild of moderately strong analgesics was at a similar low level at the
      beginning and end of the 10-year period.

PMID- 11450623
TI  - [Fever and calf tenderness after travel in Thailand: murine typhus and deep vein
      thrombosis].
AB  - HISTORY AND CLINICAL FINDINGS: A 37-year-old German fell ill with fever and
      diffuse headaches 3 weeks after flying to Thailand for a holiday. Because of
      increasing sickness he began his return (13 h by train then 11 h by plane).
      Besides a temperature of 39.3 degrees C he presented with a unproductive cough
      and pain in his left calf. On examination there were no other pathological
      findings than a borderline tachycardia, mild hypotension and signs of
      dehydration. INVESTIGATIONS: Laboratory tests showed elevated inflammatory
      parameters (CRP 77.8 mg/l, ESR 36 mm), normal range of leucocytes with obvious
      shift to the left, mild thrombocytopenia and elevated liver enzymes. The Weil
      Felix-reaction revealed a high antibody titre against OX 19, the IFT for
      Rickettsia typhi a significant increase of IgM with seroconversion for IgG.
      Duplex ultrasonography and phlebography confirmed a phlebothrombosis of the left
      upper thigh. DIAGNOSIS: Murine typhus and deep vein thrombosis of the left upper
      leg. TREATMENT AND COURSE: Suspecting typhoid fever with ciprofloxacin was
      started. In less then 2 days the patient became afebrile and recovered. The deep
      vein thrombosis was treated with low-molecular-weight heparin (Tinzaparin)
      overlapping with phenprocoumon. CONCLUSION: In patients with fever after travel
      to tropical or subtropical areas (including southern Europe) the diagnosis of
      murine typhus should be considered, especially if concomitant with thromboembolic
      events. The Weil-Felix-reaction is a helpful screening test supplemented by
      Rickettsia specific serologic tests. Overall a higher risk of thrombosis should
      be taken into account after long sedentary travel.

PMID- 11450624
TI  - [A case of primary zopiclone dependence].
AB  - MEDICAL HISTORY: A 59-year-old female patient reported an increasing intake of up
      to 20 pills of zopiclone per day (150 mg) during the past 3 years. The dose
      increase was associated with euphoria and subjectively improved fitness. The
      patient suffered from anxiety and inner restlessness when trying to discontinue
      the medication, as well as from fatigue and forgetfulness when on medication. The
      medical history was free of psychiatric disorders and abuse of psychoactive
      substances. CLINICAL FINDINGS: Apart from mild attention and concentration
      deficits with a mildly depressed mood the psychiatric findings were normal.
      COURSE AND TREATMENT: Consistent with the preliminary diagnosis of a primary non
      benzodiazepine dependence (zopiclone), after withdrawal of zopiclone the patient
      suffered from inner restlessness and psychomotor agitation, vague abdominal pain,
      and hypertension. The symptoms subsided after administration and subsequent
      gradual discontinuation of diazepam. CONCLUSION: Zopiclone dependence has
      repeatedly been reported in patients with pre-existing substance-related
      addictions, and in patients with other psychiatric disorders. Primary zopiclone
      dependence may be regarded as rare. Despite the low dependence potential of non
      benzodiazepine hypnotics, the indication of prescription should be thoroughly
      considered.

PMID- 11450625
TI  - [Progressive limb-girdle muscular dystrophy].

PMID- 11450626
TI  - [Sensory function and functional diseases of the gastrointestinal system].

PMID- 11450627
TI  - [Stroke, cholesterol and statins--are there new data about stroke prevention?].

PMID- 11450628
TI  - [Evaluation of hospital emergency services working hours. Opinion of the Work
      Court of Gotha of 3.04.2001].

PMID- 11450629
TI  - [Addison crisis].

PMID- 11450630
TI  - [Therapy of familial hypercholesterolemia].

PMID- 11450632
TI  - [Subject and author index, volume 127, year 2000].

PMID- 11450631
TI  - [Perspectives in surgery in the 21st century. Proceedings of the 117th Congress
      of the German Society for Surgery. 2-6 May 2000, Berlin, Germany. Proceedings and
      abstracts].

PMID- 11450633
TI  - Cumulative author, subject, compound and special issue indexes, volumes 726-750.

PMID- 11450634
TI  - The Ellenhorn Award: Introduction of Dr. Frederick Lovejoy.

PMID- 11450635
TI  - Clinical toxicology: built better than they knew. Reflections on yesterday, today
      and tomorrow.

PMID- 11450636
TI  - [XXXVth Angiology Meeting of the French-speaking Community. Paris, France, 21-23
      March 2001. Abstracts].

PMID- 11450637
TI  - Abstracts from the VIIIth International Symposium on Blood Substitutes. November
      8-11, 2000. San Diego, California, USA.

PMID- 11450638
TI  - American Society for Laser Medicine and Surgery 21st annual meeting. New Orleans,
      Louisiana, USA. April 20-22, 2001. Abstracts.

PMID- 11450639
TI  - [15th Congress of the German-speaking Association for Intraocular Lens
      Implantation and Refractive Surgery. 16-17 February 2001, Bremen. Abstracts].

PMID- 11450640
TI  - Abstracts of the 9th Annual Meeting of the European Society of Anaesthesiologists
      with the Swedish Society of Anaesthesiology. Gothenburg, Sweden, 7-10 April 2001.

PMID- 11450641
TI  - [Acute- and chronic-phase psychiatric care and rehabilitation].

PMID- 11450642
TI  - Abstracts of the 6th Meeting of the International Federation of Teratology
      Societies and the 40th annual meeting of the Japanese Teratology Society. Matsue,
      Japan, July 12-14, 2000 and Hiroshima, Japan, July 17, 2000.

PMID- 11450643
TI  - [1981-2001, Twenty years of Luso-Brasileira Cardiology, present and future].

PMID- 11450644
TI  - Abstracts of ESEM 2001. The 6th Biennial Conference of the European Society for
      Engineering and Medicine. Belfast, Northern Ireland, 3-5 May 2001.

PMID- 11450645
TI  - [Neurology Meeting of the French-speaking Community. Lyon, France, 18-21 April
      2001. Abstracts].

PMID- 11450646
TI  - Abstracts of the 8th International Conference on Human Antibodies and Hybridomas.
      23-25 April 2001. Prague, Check Republic.

PMID- 11450647
TI  - Belgian Biochemistry and Molecular Biology Society meetings #174, #175, #176.
      February, May and December 2000. Abstracts.

PMID- 11450649
TI  - [XXII Portuguese Congress of Cardiology. Vilamoura, Portugal, 8-11 April 2001.
      Abstracts].

PMID- 11450648
TI  - [Membership list, 2001].

PMID- 11450650
TI  - Acute problems of the hemorheological analysis.

PMID- 11450651
TI  - Faculty of Medical Sciences 9th Annual Research Conference. November 9, 2000.
      Kingston, Jamaica. Abstracts.

PMID- 11450652
TI  - Abstracts of the 29th National Congress of the Italian Society of Histochemistry.
      April 23-25, 2001. Anacapri, Italy.

PMID- 11450653
TI  - Proceedings of the Physiological Society scientific meeting held at University of
      Oxford, 19-21 March 2001.

PMID- 11450654
TI  - Inhaled sodium cromoglycate.

PMID- 11450655
TI  - BTS guidelines on TB.

PMID- 11450657
TI  - [Abstracts of the 39th Poland-wide Conference of Medical Students. April 20,
      2001. Krakow].

PMID- 11450656
TI  - Occlusion of chest drain bottle air outlet.

PMID- 11450658
TI  - [21st Yugoslav Surgery Congress. Belgrad, 21-24 March 2001. Abstracts].

PMID- 11450659
TI  - High-altitude illness.

PMID- 11450660
TI  - Lyme disease.

PMID- 11450661
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 21-2001. A 31-year-old man with an apparent seizure and a mass in
      the right parietal lobe.

PMID- 11450662
TI  - Doxycycline for tick bites--not for everyone.

PMID- 11450663
TI  - Inequalities in health.

PMID- 11450664
TI  - Research involving human subjects in developing countries.

PMID- 11450665
TI  - Ethical issues in the design and conduct of clinical trials in developing
      countries.

PMID- 11450666
TI  - Recommendation for caution with irinotecan, fluorouracil, and leucovorin for
      colorectal cancer.

PMID- 11450667
TI  - Recommendation for caution with irinotecan, fluorouracil, and leucovorin for
      colorectal cancer.

PMID- 11450668
TI  - Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

PMID- 11450669
TI  - Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

PMID- 11450670
TI  - High serum IgG4 concentrations in patients with sclerosing pancreatitis.

PMID- 11450671
TI  - La Crosse encephalitis in children.

PMID- 11450672
TI  - Paternal and maternal components of the predisposition to preeclampsia.

PMID- 11450673
TI  - Paternal and maternal components of the predisposition to preeclampsia.

PMID- 11450674
TI  - Coinfection with Borrelia burgdorferi and the agent of human granulocytic
      ehrlichiosis.

PMID- 11450675
TI  - Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after
      an Ixodes scapularis tick bite.
AB  - BACKGROUND: It is unclear whether antimicrobial treatment after an Ixodes
      scapularis tick bite will prevent Lyme disease. METHODS: In an area of New York
      where Lyme disease is hyperendemic we conducted a randomized, double-blind,
      placebo-controlled trial of treatment with a single 200-mg dose of doxycycline in
      482 subjects who had removed attached I. scapularis ticks from their bodies
      within the previous 72 hours. At base line, three weeks, and six weeks, subjects
      were interviewed and examined, and serum antibody tests were performed, along
      with blood cultures for Borrelia burgdorferi. Entomologists confirmed the species
      of the ticks and classified them according to sex, stage, and degree of
      engorgement. RESULTS: Erythema migrans developed at the site of the tick bite in
      a significantly smaller proportion of the subjects in the doxycycline group than
      of those in the placebo group (1 of 235 subjects [0.4 percent] vs. 8 of 247
      subjects [3.2 percent], P<0.04). The efficacy of treatment was 87 percent (95
      percent confidence interval, 25 to 98 percent). Objective extracutaneous signs of
      Lyme disease did not develop in any subject, and there were no asymptomatic
      seroconversions. Treatment with doxycycline was associated with more frequent
      adverse effects (in 30.1 percent of subjects, as compared with 11.1 percent of
      those assigned to placebo; P<0.001), primarily nausea (15.4 percent vs. 2.6
      percent) and vomiting (5.8 percent vs. 1.3 percent). Erythema migrans developed
      more frequently after untreated bites from nymphal ticks than after bites from
      adult female ticks (8 of 142 bites [5.6 percent] vs. 0 of 97 bites [0 percent],
      P=0.02) and particularly after bites from nymphal ticks that were at least
      partially engorged with blood (8 of 81 bites [9.9 percent], as compared with 0 of
      59 bites from unfed, or flat, nymphal ticks [0 percent]; P=0.02). CONCLUSIONS: A
      single 200-mg dose of doxycycline given within 72 hours after an I. scapularis
      tick bite can prevent the development of Lyme disease.

PMID- 11450676
TI  - Two controlled trials of antibiotic treatment in patients with persistent
      symptoms and a history of Lyme disease.
AB  - BACKGROUND: It is controversial whether prolonged antibiotic treatment is
      effective for patients in whom symptoms persist after the recommended antibiotic
      treatment for acute Lyme disease. METHODS: We conducted two randomized trials:
      one in 78 patients who were seropositive for IgG antibodies to Borrelia
      burgdorferi at the time of enrollment and the other in 51 patients who were
      seronegative. The patients received either intravenous ceftriaxone, 2 g daily for
      30 days, followed by oral doxycycline, 200 mg daily for 60 days, or matching
      intravenous and oral placebos. Each patient had well-documented, previously
      treated Lyme disease but had persistent musculoskeletal pain, neurocognitive
      symptoms, or dysesthesia, often associated with fatigue. The primary outcome
      measures were improvement on the physical- and mental-health-component summary
      scales of the Medical Outcomes Study 36-item Short-Form General Health Survey (SF
      36)--a scale measuring the health-related quality of life--on day 180 of the
      study. RESULTS: After a planned interim analysis, the data and safety monitoring
      board recommended that the studies be discontinued because data from the first
      107 patients indicated that it was highly unlikely that a significant difference
      in treatment efficacy between the groups would be observed with the planned full
      enrollment of 260 patients. Base-line assessments documented severe impairment in
      the patients' health-related quality of life. In intention-to-treat analyses,
      there were no significant differences in the outcomes with prolonged antibiotic
      treatment as compared with placebo. Among the seropositive patients who were
      treated with antibiotics, there was improvement in the score on the physical
      component summary scale of the SF-36, the mental-component summary scale, or both
      in 37 percent, no change in 29 percent, and worsening in 34 percent; among
      seropositive patients receiving placebo, there was improvement in 40 percent, no
      change in 26 percent, and worsening in 34 percent (P=0.96 for the comparison
      between treatment groups). The results were similar for the seronegative
      patients. CONCLUSIONS: There is considerable impairment of health-related quality
      of life among patients with persistent symptoms despite previous antibiotic
      treatment for acute Lyme disease. However, in these two trials, treatment with
      intravenous and oral antibiotics for 90 days did not improve symptoms more than
      placebo.

PMID- 11450677
TI  - Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in
      chronic renal-allograft rejection.
AB  - BACKGROUND: Tissue remodeling depends on mesenchymal cells (fibroblasts and
      myofibroblasts) and is a prominent feature of chronic renal-transplant rejection.
      It is not known whether the mesenchymal cells that participate in remodeling
      originate locally or from circulating precursor cells. METHODS: We obtained
      biopsy specimens of renal allografts from six male recipients of an allograft
      from a female donor, four female recipients of an allograft from a male donor,
      two male recipients of an allograft from a male donor, and two female recipients
      of an allograft from a female donor. All the allografts were undergoing chronic
      rejection. All but two specimens were obtained within six months after
      transplantation. We used immunohistochemical methods to identify mesenchymal
      cells with smooth-muscle alpha-actin and in situ hybridization to identify
      mesenchymal cells with Y-chromosome DNA. RESULTS: No Y-chromosome bodies were
      identified in the case of the two renal-allograft specimens in which both the
      donor and the recipient were female. In the case of the two renal-allograft
      specimens in which both the donor and the recipient were male, approximately 40
      percent of mesenchymal cells contained a Y-chromosome body. In the case of the
      six specimens in which the donor was female and the recipient was male, a mean
      (+/-SD) of 34+/-16 percent of mesenchymal cells in the neointima, 38+/-12 percent
      of such cells in the adventitia, and 30+/-7 percent of such cells in the
      interstitium contained the Y-chromosomal marker, indicating that they originated
      from the recipient rather than the donor. In the case of the four renal-allograft
      specimens in which the donor was male and the recipient was female, the
      respective values were 24+/-15 percent, 33+/-9 percent, and 23+/-8 percent,
      indicating a persistent population of donor mesenchymal cells. CONCLUSIONS: The
      presence of mesenchymal cells of host origin in the vascular and interstitial
      compartments of renal allografts undergoing chronic rejection provides evidence
      that a circulating mesenchymal precursor cell has the potential to migrate to
      areas of inflammation.

PMID- 11450678
TI  - Images in clinical medicine. Giant coronary-artery aneurysm in Kawasaki's
      disease.

PMID- 11450679
TI  - Neighborhood of residence and incidence of coronary heart disease.
AB  - BACKGROUND: Where a person lives is not usually thought of as an independent
      predictor of his or her health, although physical and social features of places
      of residence may affect health and health-related behavior. METHODS: Using data
      from the Atherosclerosis Risk in Communities Study, we examined the relation
      between characteristics of neighborhoods and the incidence of coronary heart
      disease. Participants were 45 to 64 years of age at base line and were sampled
      from four study sites in the United States: Forsyth County, North Carolina;
      Jackson, Mississippi; the northwestern suburbs of Minneapolis; and Washington
      County, Maryland. As proxies for neighborhoods, we used block groups containing
      an average of 1000 people, as defined by the U.S. Census. We constructed a
      summary score for the socioeconomic environment of each neighborhood that
      included information about wealth and income, education, and occupation. RESULTS:
      During a median of 9.1 years of follow-up, 615 coronary events occurred in 13,009
      participants. Residents of disadvantaged neighborhoods (those with lower summary
      scores) had a higher risk of disease than residents of advantaged neighborhoods,
      even after we controlled for personal income, education, and occupation. Hazard
      ratios for coronary events in the most disadvantaged group of neighborhoods as
      compared with the most advantaged group--adjusted for age, study site, and
      personal socioeconomic indicators--were 1.7 among whites (95 percent confidence
      interval, 1.3 to 2.3) and 1.4 among blacks (95 percent confidence interval, 0.9
      to 2.0). Neighborhood and personal socioeconomic indicators contributed
      independently to the risk of disease. Hazard ratios for coronary heart disease
      among low-income persons living in the most disadvantaged neighborhoods, as
      compared with high-income persons in the most advantaged neighborhoods were 3.1
      among whites (95 percent confidence interval, 2.1 to 4.8) and 2.5 among blacks
      (95 percent confidence interval, 1.4 to 4.5). These associations remained
      unchanged after adjustment for established risk factors for coronary heart
      disease. CONCLUSIONS: Even after controlling for personal income, education, and
      occupation, we found that living in a disadvantaged neighborhood is associated
      with an increased incidence of coronary heart disease.

PMID- 11450680
TI  - Pancreatic tumors show high levels of hypoxia: regarding Koong et al. IJROBP
      2000;48:919-922.

PMID- 11450681
TI  - How evolution came to Italy--the Turin connection.

PMID- 11450682
TI  - [Patient's perspectives with regard to anesthesia services].
AB  - PURPOSE: Whereas patients most often select their surgeon, they don't usually
      select their anesthesiologist. Further, anesthesia frequently involves different
      physicians at different stages perioperatively. This inability to choose and the
      multiplicity of interveners may reduce patient satisfaction. Our study examined
      patients' willingness to choose their anesthesiologist for the operation, as well
      as their opinion on the way anesthesia is practiced presently. CLINICAL FEATURES:
      Nine hundred and twelve patients (mean age 51 +/- 16 yr, 58% moles) were
      requested, immediately after the preoperative visit, to choose their
      anesthesiologist for the operation. The request was formuled by a nurse, in the
      absence of the anesthesiologist, in order to avoid a courteous response. After
      surgery, prior to leaving the hospital, patients were invited to give their
      opinion on the anesthesia core received and to name the anesthesiologist(s) and
      surgeon involved. RESULTS: Women chose an anesthesiologist more frequently than
      men, but only 34% of patients overall elected to do so. Eighty percent of
      patients were cared for by an anesthesiologist other than the one seen at the
      preoperative visit. Four percent of patients regretted the change. Patients
      recalled the surgeon's name more frequently (60%) than the attending
      anesthesiologist's (4%). CONCLUSION: In France, the preoperative visit is
      required by law and must precede the operation by at least 48 hr. Despite this
      preoperative interview, patients were unwilling to choose the anesthesiologist
      responsible for surgery, did not object to multiple interveners and seldom
      remembered their anesthesiologist's name. Efforts to improve the image of the
      profession are required.

PMID- 11450683
TI  - Tissue reactions of polypropylene mesh used in maxillofacial trauma.
AB  - Four 1-cm2 fragments of polypropylene mesh were implanted in the subcutaneous
      tissue of each of 10 albino rats to evaluate biocompatibility. A straight
      longitudinal incision was made on the back of these animals and histological
      analysis was carried out at 7, 15 and 30 days. At 7 days, there was a mild
      inflammatory reaction around the implanted material. On day 15, the inflammatory
      process continued being discrete. The inflammatory reaction decreased
      significantly by day 30, when mild inflammation with cell infiltrate was
      observed, as well as the formation of a layer of fibrous tissue surrounding the
      implanted mesh. These results show the biocompatibility of the polypropylene mesh
      and support its use in oral and maxillofacial surgery.

PMID- 11450684
TI  - Oral manifestations related to immunosuppression degree in HIV-positive children.
AB  - Oral manifestations often found in HIV-infected children are frequently the first
      clinical sign of the infection. This article aims to report the prevalence of
      oral manifestations in soft tissues and their relationship with the degree of
      immunosuppression in 80 HIV-infected patients (average age 6.30 +/- 3.32 years
      old) at the IPPMG-UFRJ. Thirty children (38%) presented some type of oral lesion
      and the percentage of CD4 was lower than that found in lesion-free children (p <
      0.05); 22.5% presented candidiasis, 17.5% gingivitis, 8.8% enlargement of
      parotids, 1.3% herpes simplex and 1.3% hairy leukoplakia. Of the 30 children with
      lesions, 70% showed severe immunosuppression, 23.3% moderate immunosuppression
      and in only 6.7% was immunosuppression absent. Oral manifestations were directly
      related to the degree of immunosuppression and such lesions can be considered as
      indicators of the progression of the HIV infection in children.

PMID- 11450685
TI  - Effectiveness of the ProFile.04 Taper Series 29 files in removal of gutta-percha
      root fillings during curved root canal retreatment.
AB  - The purpose of this in vitro study was to evaluate the capacity of ProFile.04
      Taper Series 29 files to remove gutta-percha during curved root canal
      retreatment. Forty-four mandibular molars whose mesial roots presented between 26
      and 40 degrees of curvature, determined by Schneider's method, were selected. The
      root canals were enlarged to ISO size 35 and obturated with laterally condensed
      gutta-percha using Sealer 26. The teeth were randomly divided into three groups
      for gutta-percha removal: GI: size 2 Gates Glidden drills; GII: size 6 ProFile.04
      Taper Series 29 files; GIII: size 7 ProFile.04 Taper Series 29 files. The
      penetration of the instruments was measured with millimetered x-rays and clinical
      observation. The ProFile.04 Taper Series 29 files removed the endodontic filling
      material better than the Gates Glidden files.

PMID- 11450686
TI  - Influence of gamma irradiation on a natural source of peroxidase and its effect
      in the reagentless amperometric biosensor for hydrogen peroxide.
AB  - Peroxidase was extracted from a natural source (turnip) and irradiated with 60Co
      (0.1 kGy). It was then used in the construction of biosensors for hydrogen
      peroxide determination, in order to study the effect of the gamma irradiation on
      the performance of the biosensors. The biosensors were constructed using two
      immobilization procedures: cross-linking with glutaraldehyde and covalent binding
      through carbodiimide. The biosensor prepared using covalent binding through
      carbodiimide showed a higher sensitivity for H2O2. A good enhancement in
      stability and sensitivity was obtained for the biosensors from irradiated
      material, when compared to biosensors prepared with non-irradiated enzyme.
      However, the initial linear response range (1.0 to 10.0 mmol dm-3) and response
      time (0.5 s) were equal with or without irradiation.

PMID- 11450687
TI  - Recent advances in the treatment of vaccine-associated sarcomas.
AB  - This article reviews the background information about vaccine-associated sarcomas
      followed by diagnostic procedures essential to understand how to determine the
      extent of the primary and metastatic tumor as well as to understand the general
      health of the patient. It also addresses the importance of understanding the
      nonmedical needs of the client who is faced with this perplexing problem.

PMID- 11450688
TI  - Left ventricular relaxation abnormality is detectable by analysis of the
      relaxation time constant in patients with atrial fibrillation.
AB  - Left ventricular (LV) contractility is constantly changing during atrial
      fibrillation (AF), which is dependent on the force-interval relationships.
      However, no information has been available on LV relaxation in patients with both
      AF and impaired LV systolic function. LV pressure was measured with a catheter
      tipped micromanometer and the time constant of isovolumic LV pressure decline
      (tau(bf)) was calculated with best exponential fitting from more than 10
      consecutive beats. Patients with AF (5 with mitral valvular disease, 6 with
      idiopathic dilated cardiomyopathy, and 1 with no underlying disease) were
      subdivided into 2 groups: group A, with ejection fraction (EF) <0.5 (n=7); and
      group B, with EF > or =0.5 (n=5). Linear correlation coefficients (r) between tau
      and RR2, RR2/RR1, LV peak systolic pressure (peak LVP) were calculated. Although
      tau did not show a discrepancy between the 2 groups, tau(bf) correlated better
      with RR2/RR1 only in the group A patients. The relation between tau and peak LVP
      showed a good correlation with a steep slope (R, Deltatau/Deltapeak LVP) only in
      the group A patients (accentuated afterload-dependence). R was significantly
      different between the 2 groups. Thus, a beat-to-beat analysis of tau may be a
      practical and feasible way for detecting LV relaxation abnormality in patients
      with AF.

PMID- 11450689
TI  - Effect of verapamil on prevention of atrial fibrillation in patients implanted
      with an implantable atrial defibrillator.
AB  - BACKGROUND: The role of verapamil in the prevention of atrial fibrillation (AF)
      in patients with recurrent AF is unknown. HYPOTHESIS: The aim of this study was
      to evaluate the effect of verapamil on the prevention of AF in patients implanted
      with an implantable atrial defibrillator (IAD). METHODS: The effects of verapamil
      (240 mg/day) on the total duration of AF, number of AF recurrences, and number of
      cardioversions were prospectively evaluated in a randomized, crossover fashion
      over an 8-week period in 11 patients (9 men, 2 women; mean age: 60 +/- 6 years)
      implanted with an IAD. RESULTS: Implantable atrial defibrillators successfully
      converted 13 of 14 (93%) spontaneous episodes of AF. There was no significant
      difference in the efficacy of cardioversion (86 vs. 100%, p = 0.8), the total
      duration of AF (173 +/- 198 vs. 270 +/- 241 h, p = 0.5), the number of AF
      episodes (8.5 +/- 9.0 vs. 9.3 +/- 10.2, p = 0.3), and the number of
      cardioversions (1.7 +/- 2.4 vs. 1.8 +/- 2.1 p = 0.7) with or without treatment
      with verapamil. CONCLUSIONS: The results of the present study suggest that
      treatment with verapamil has no significant effect on the prevention of AF in
      patients treated with an LAD.

PMID- 11450690
TI  - Abstracts of the First International Symposium on Intensive Care and Emergency
      Medicine for Latin America. Sao Paulo, Brazil, 26-29 June 2001.

PMID- 11450691
TI  - Abstracts of the 10th European Stroke Conference. Lisbon, Portugal, May 16-19,
      2001.

PMID- 11450692
TI  - 6th European Society of Neurosonology and Cerebral Hemodynamics meeting and 9th
      Neurosonology Research Group of the World Federation of Neurology meeting.
      Lisbon, Portugal, May 13-15, 2001. Abstracts.

PMID- 11450693
TI  - Abstracts of the XXXVI annual meeting of the Society for the Spontaneously
      Hypertensive Rat. July 15-16, 2000. Kyoto, Japan.

PMID- 11450694
TI  - Quantitative trait loci for femoral and lumbar vertebral bone mineral density in
      C57BL/6J and C3H/HeJ inbred strains of mice.
AB  - Significant differences in vertebral (9%) and femoral (50%) adult bone mineral
      density (BMD) between the C57BL/6J (B6) and C3H/HeJ (C3H) inbred strains of mice
      have been subjected to genetic analyses for quantitative trait loci (QTL). Nine
      hundred eighty-six B6C3F2 females were analyzed to gain insight into the number
      of genes that regulate peak BMD and their locations. Femurs and lumbar vertebrae
      were isolated from 4-month-old B6C3F2 females at skeletal maturity and then BMD
      was determined by peripheral quantitative computed tomography (pQCT). Estimates
      of BMD heritability were 83% for femurs and 72% for vertebrae. Genomic DNA from
      F2 progeny was screened for 107 polymerase chain reaction (PCR)-based markers
      discriminating B6 and C3H alleles on all 19 autosomes. The regression analyses of
      markers on BMD revealed ten chromosomes (1, 2, 4, 6, 11, 12, 13, 14, 16, and 18)
      carrying QTLs for femurs and seven chromosomes (1, 4, 7, 9, 11, 14, and 18)
      carrying QTLs for vertebrae, each with log10 of the odds ratio (LOD) scores of
      2.8 or better. The QTLs on chromosomes (Chrs) 2, 6, 12, 13, and 16 were unique to
      femurs, whereas the QTLs on Chrs 7 and 9 were unique to vertebrae. When the two
      bone sites had a QTL on the same chromosome, the same marker had the highest,
      although different, LOD score. A pairwise comparison by analysis of variance
      (ANOVA) did not reveal significant gene x gene interactions between QTLs for
      either bone site. BMD variance accounted for by individual QTLs ranged from 1% to
      10%. Collectively, the BMD QTLs for femurs accounted for 35.1% and for vertebrae
      accounted for 23.7 % of the F2 population variances in these bones. When mice
      were homozygous c3/c3 in the QTL region, 8 of the 10 QTLs increased, while the
      remaining two QTLs on Chrs 6 and 12 decreased, femoral BMD. Similarly, when mice
      were homozygous c3/c3 in the QTL region for the vertebrae, five of the seven QTLs
      increased, while two QTLs on Chrs 7 and 9 decreased, BMD. These findings show the
      genetic complexity of BMD with multiple genes participating in its regulation.
      Although 5 of the 12 QTLs are considered to be skeleton-wide loci and commonly
      affect both femurs and vertebrae, each of the bone sites also exhibited unique
      QTLs. Thus, the BMD phenotype can be partitioned into its genetic components and
      the effects of these loci on normal bone biology can be determined. Importantly,
      the BMD QTLs that we have identified are in regions of the mouse genome that have
      known human homology, and the QTLs will become useful experimental tools for
      mechanistic and therapeutic analyses of bone regulatory genes.

PMID- 11450695
TI  - Breaking down bone strength: a perspective on the future of skeletal genetics.

PMID- 11450696
TI  - Discordance between changes in bone mineral density measured at different
      skeletal sites in perimenopausal women--implications for assessment of bone loss
      and response to therapy: The Danish Osteoporosis Prevention Study.
AB  - Assessing bone loss and gain is important in clinical decision-making, both in
      evaluating treatment and in following untreated patients. The aim of this study
      was to correlate changes in bone mineral density (BMD) at different skeletal
      sites during the first 5 years after menopause and determine if forearm
      measurements can substitute for dual-energy X-ray absorptiometry (DXA) of the
      spine and hip. BMD was measured at 0, 1, 2, 3, and 5 years using Hologic 1000/W
      and 2000 densitometers in 2,016 perimenopausal women participating in a national
      cohort study. This analysis comprises 1,422 women remaining in the study after 5
      years without changes to their initial treatment (hormone-replacement therapy
      [HRT], n = 497, or none, n = 925). Despite correlated rates of change between
      forearm and spine (r2 = 0.11; p < 0.01), one-half of those who experienced a
      significant decrease in spine BMD at 5 years showed no significant fall in
      forearm BMD (sensitivity, 50%; specificity, 85%; kappa = 0.25). The total hip had
      significant better agreement with spine (sensitivity, 63%; specificity, 85%;
      kappa = 0.37; p < 0.01). Analysis of quartiles of change also showed significant
      better agreement with spine and whole body for the total hip than for the femoral
      neck or ultradistal (UD) forearm. In a logistic regression analysis for
      identification of group (HRT or control), the prediction was best for whole body
      (82.6%) and spine (80.9%), followed by total hip (78.5%) and forearm (74.7%). In
      conclusion, changes at the commonly measured sites are discordant, and DXA of the
      forearm is less useful than DXA of the hip or spine in determining the overall
      skeletal response to therapy or assessing bone loss in untreated women.

PMID- 11450697
TI  - Stimulation of interleukin-6 promoter by parathyroid hormone, tumor necrosis
      factor alpha, and interleukin-1beta in UMR-106 osteoblastic cells is inhibited by
      protein kinase C antagonists.
AB  - To investigate the level at which protein kinase C (PKC) regulates expression of
      interleukin-6 (IL-6) in osteoblastic cells, effects of several PKC antagonists
      and PKC down-regulation by phorbol ester were studied in UMR-106 osteoblastic
      cells that had been transiently transfected with a -224/+11-base pair (bp) IL-6
      promoter coupled to a luciferase reporter. Parathyroid hormone (PTH) elicited a
      dose-dependent stimulation of the IL-6 promoter expression, with significant
      increases produced by 5 h of treatment with concentrations of PTH as low as 10(
      14) M. The increase in IL-6 promoter expression was inhibited by the PKC
      antagonists GF109203X, 30 nM to 1 microM, and calphostin C, 250 nM. Prior down
      regulation of PKC with 100 nM phorbol-12,13-dibutyrate (PDBU) for 48 h inhibited
      the PTH effect as well as the smaller stimulatory effects elicited by tumor
      necrosis factor alpha (TNF-alpha), 10(-9)-10(-8) M, and by IL-1beta, 1-10 ng/ml.
      In contrast to these findings, the stimulatory effects of PTH, TNF-alpha, and IL
      1beta on the IL-6 promoter expression were enhanced by staurosporine. Treatment
      with GF109203X or down-regulation of PKC with PDBU prevented the stimulatory
      effects of staurosporine. PKC activity was increased by staurosporine. The
      findings with staurosporine are consistent with our earlier observations that
      this agent enhances the calcium signaling and bone resorption elicited by PTH.
      The studies support the role of PKC in the stimulatory effects of PTH, TNF-alpha,
      and IL-1beta on IL-6 expression.

PMID- 11450698
TI  - Col1a1-driven transgenic markers of osteoblast lineage progression.
AB  - The modular organization of the type I collagen promoter allows creation of
      promoter-reporter constructs with preferential activity in different type I
      collagen-producing tissues that might be useful to mark cells at different stages
      of osteoblastic differentiation. Primary marrow stromal cell (MSC) and mouse
      calvarial osteoblast (mCOB) cultures were established from transgenic mice
      harboring different Col1a1 promoter fragments driving chloramphenicol
      acetyltransferase (CAT). In these models, Col1a1 messenger RNA (mRNA) and
      alkaline phosphatase (ALP) are the first markers of differentiation appearing
      soon after the colonies develop. Bone sialoprotein (BSP) is detected 2-3 days
      later, followed by osteocalcin (OC) expression and nodule mineralization. A 3.6
      Col1a1 fragment (ColCAT3.6) initiated activity concomitant with ALP staining and
      type I collagen mRNA expression. In contrast, a 2.3 Col1a1 fragment (ColCAT2.3)
      became active coincident with BSP expression. The pattern of transgene expression
      assessed by immunostaining was distinctly different. ColCAT3.6 was expressed
      within and at the periphery of developing nodules whereas the ColCAT2.3
      expression was restricted to the differentiated nodules. The feasibility of using
      green fluorescent protein (GFP) as a marker of osteoblast differentiation was
      evaluated in ROS17/2.8 cells. A 2.3-kilobase (kb) Col1a1 promoter driving GFP
      (pOB4Col2.3GLP) was stably transfected into the cell line and positive clones
      were selected. Subcultures lost and then regained GFP expression that was
      localized in small clusters of cells throughout the culture. This suggests that
      expression from the 2.3-kb Col1A1 fragment is determined by the state of
      differentiation of the ROS17/2.8 cells. Col1a1 transgenes should be useful in
      appreciating the heterogeneity of a primary or immortalized culture undergoing
      osteoblastic differentiation.

PMID- 11450699
TI  - Transforming growth factor-beta induces osteoclast ruffling and chemotaxis:
      potential role in osteoclast recruitment.
AB  - Transforming growth factor-beta (TGF-beta) is released from the matrix during
      bone resorption and has been implicated in the pathogenesis of giant cell tumors
      of bone and the expansion of breast cancer metastases in bone. Because
      osteoclasts mediate tumor-induced osteolysis, we investigated whether TGF-beta
      stimulates osteoclast recruitment. Osteoclasts were isolated from rat long bones
      and time-lapse video microscopy was used to monitor their morphology and
      motility. Within 5 minutes, TGF-beta (0.1 nM) induced dynamic ruffling, with 65%
      of osteoclasts displaying membrane ruffles compared with 35% in untreated
      controls. Over a 2-h period, osteoclasts exhibited significant directed migration
      toward a source of TGF-beta, indicating chemotaxis. echistatin, an alphavbeta3
      integrin blocker that inhibits macrophage colony-stimulating factor (M-CSF)
      induced osteoclast migration, did not prevent the migration of osteoclasts toward
      TGF-beta. In contrast, a beta1 integrin blocking antibody inhibited osteoclast
      chemotaxis toward TGF-beta but not M-CSF. These data indicate the selective use
      of integrins by osteoclasts migrating in response to different chemotaxins. In
      addition, wortmannin and U0126 inhibited TGF-beta-induced chemotaxis, suggesting
      involvement of the phosphatidylinositol 3 (PI 3) kinase and mitogen-activated
      protein (MAP) kinase signaling pathways. Physiologically, TGF-beta, may
      coordinate osteoclast activity by recruiting osteoclasts to existing sites of
      resorption. Pathologically, TGF-beta-induced osteoclast recruitment may be
      critical for expansion of primary and metastatic tumors in bone.

PMID- 11450700
TI  - Organization of cytoskeletal F-actin, G-actin, and gelsolin in the adhesion
      structures in cultured osteoclast.
AB  - Immunofluorescence using Gc protein (group-specific component or vitamin D
      binding protein [DBP]) as a marker of G-actin showed that nonfilamentous,
      monomeric G-actin is a component of the podosomes of osteoclasts cultured on
      glass plates or bone slices. Typical individual podosomes of the well-spread
      cells on glass plates were rosette in form. When viewed from the basolateral
      surface, the core portion of the dotlike podosomes was associated with packed F
      actin filaments surrounded by G-actin organized in a ringlike structure. The
      podosomes, when viewed perpendicular to the substrate, showed a conical shape as
      a bundle of short F-actin core and a ring of G-actin. With cell spreading on
      glass plates, the clustering of the podosomes formed a continuous belt of tightly
      packed podosomes as an adhesion structure at the paramarginal area. In addition,
      these structures were seen on the ventral cell surface. Similar changes in cell
      shape were seen in the osteoclasts when they were plated on bone slices. With the
      loss of dotlike podosomes, a continuous band of F-actin was formed around the
      resorption lacunae. It became evident then that F- and G-actin dissociated from
      each other in the podosomes. The staining patterns of G-actin varied from a
      discrete dot to a diffuse one. Toward the nonresorption phase, the osteoclasts
      lost their continuous F-actin band but dotlike podosomes appeared in the leading
      and the trailing edges. In such a cell undergoing translational movements, G
      actin was located diffusely in the cytoplasm behind the lamellipodia and along
      some segments of the leading edge. Cytochalasin B treatment caused cells to
      disorganize the actin cytoskeletal architecture, which indicated the
      disassembling of F-actin into G-actin in podosomes and disappearance of actin
      ring of cultured osteoclasts. Staining with polyclonal actin antibody or
      monoclonal beta-actin was overlapped with the distribution pattern of G- and F
      actin. Gelsolin was detected in the region of the adhesion area corresponding to
      the podosome. The observation that F-actin, G-actin, and gelsolin were detected
      in the osteoclastic adhesion structures suggests that the podosomes may represent
      sites where a rapid polymerization/depolymerization of actin occurs. These
      dynamic changes in cytoskeletal organization and reorganization of G-actin may
      reflect changes in the functional polarization of the osteoclast during the bone
      resorption cycle and suggest the important role of G-actin in the regulation of
      osteoclast adhesion.

PMID- 11450701
TI  - The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element
      in the human vitamin D receptor gene.
AB  - The major physiological activity of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the
      regulation of calcium absorption in the small intestine, and the level of vitamin
      D receptor (VDR) is an important factor in this regulation. In a previous study,
      we indicated-that the caudal-related homeodomain Cdx-2 played an important role
      in the intestine-specific transcription of the human VDR gene. In this study, the
      polymorphism was identified in the core sequence 5'-ATAAAAACTTAT-3' in the Cdx-2
      binding site in the VDR gene promoter. In 261 Japanese women with genotyped VDR
      polymorphisms, 48 were genotype Cdx-A (adenine at -3731 nucleotides [nt] relative
      to the transcription start site of human VDR gene 5-ATAAAAACTTAT), 82 were
      genotype Cdx-G (guanine at -3731 nt, 5'-GTAAAAACTTAT-3'), and 131 were genotype
      Cdx-A/G (heterozygote). In postmenopausal Japanese women, the bone mineral
      density (BMD) in the lumbar spine (L2-L4) with the Cdx-G homozygote was 12% lower
      than that with the Cdx-A homozygote (p < 0.05). In electrophoretic gel mobility
      shift assay (EMSA), the oligonucleotide with Cdx-G allele markedly decreased the
      binding to Cdx-2 compared with that in the Cdx-A allele. The transcriptional
      activity of the VDR promoter with Cdx-G allele was decreased to 70% of the Cdx-A
      allele. In addition, in the herpes simplex virus thymidine kinase promoter, the
      Cdx-2 binding element with the G allele showed significantly lower
      transcriptional activity than that of the A allele. Thus, the polymorphism in the
      Cdx-2 binding site of the VDR gene (Cdx-polymorphism) would affect the expression
      of VDR in the small intestine. In addition, this polymorphism may modulate BMD in
      postmenopausal Japanese women.

PMID- 11450702
TI  - Targeted disruption of cadherin-11 leads to a reduction in bone density in
      calvaria and long bone metaphyses.
AB  - The migration and adhesion of osteoblasts requires several classical cadherins.
      Cadherin-11, one of the classical cadherins, was expressed in mouse osteoblasts
      in skull bone and femur, revealed by immunohistochemistry. To elucidate the
      function of cadherin-11 in osteoblastogenesis, cadherin-11 null mutant mice were
      investigated. Although apparently normal at birth, Alizarin red staining of null
      mutant mice showed a reduced calcified area at the frontal suture that caused a
      round-shaped calvaria with increasing animal age to 3 months. Consequently, there
      was a reduction in bone density at the femoral metaphyses and the diploe of
      calvaria in null mutant mice. In the in vitro culture of newborn calvarial cells,
      the calcified area of mutant cells was smaller than those derived from wild-type
      littermates. These results show that absence of cadherin-11 leads to reduced bone
      density in some parts of skeletons including calvaria and long bone metaphyses,
      and thus suggest that cadherin-11 plays roles in the regulation of osteoblast
      differentiation and in the mineralization of the osteoid matrix.

PMID- 11450703
TI  - Tumor necrosis factor alpha induces expression of genes for matrix degradation in
      human chondrocyte-like HCS-2/8 cells through activation of NF-kappaB: abrogation
      of the tumor necrosis factor alpha effect by proteasome inhibitors.
AB  - Tumor necrosis factor alpha (TNF-alpha) has been suggested to induce chondrocytic
      chondrolysis in both inflammatory and degenerative joint diseases. However, its
      intracellular signaling pathway leading to the chondrolysis has not been studied
      in detail. Thus, we investigated whether TNF-alpha activates a transcription
      factor nuclear factor kappaB (NF-kappaB) in human chondrocyte-like cells (HCS
      2/8) and induces the expression of genes involved in the degradation of cartilage
      matrix. Treatment of the cells with TNF-alpha markedly increased the levels of
      matrix metalloproteinase 1 (MMP-1), MMP-3, intercellular adhesion molecule 1
      (ICAM-1), and cyclo-oxygenase 2 (COX-2) messenger RNAs (mRNAs). The increase in
      the mRNAs was associated with the activation of p65/p50 heterodimer NF-kappaB.
      IkappaB-alpha and IkappaB-beta, cytoplasmic molecules preventing the nuclear
      translocation of NF-kappaB, were degraded rapidly by TNF-alpha followed by their
      synthesis to the basal level. Treatment with proteasome inhibitors inhibited the
      degradation of both IkappaB-alpha and IkappaB-beta and prevented the TNF-alpha
      dependent nuclear translocation of p65. Furthermore, the inhibitors completely
      prevented the TNF-alpha-dependent induction of MMP-1, MMP-3, ICAM-1, and COX-2
      mRNAs. Thus, it is shown that the activation of p65/p50 NF-kappaB by TNF-alpha
      plays a cardinal role in inducing the expression of MMP-1, MMP-3, ICAM-1, and COX
      2 genes, which are involved in matrix degradation and inflammatory reaction in
      chondrocytes, leading to chondrocytic chondrolysis.

PMID- 11450704
TI  - Activation of latent transforming growth factor beta1 by stromelysin 1 in
      extracts of growth plate chondrocyte-derived matrix vesicles.
AB  - Previous studies have shown that matrix vesicles isolated from cultures of
      costochondral growth zone chondrocytes and treated with 1alpha,25
      dihydroxyvitamin D3 [1alpha,25(OH)2D3] can activate recombinant human latent
      transforming growth factor beta1 (rhTGF-beta1). It is unknown what enzyme or
      other factor in the extracellular organelles is responsible for the activation.
      This study tested the hypothesis that enzymes present in matrix vesicles can
      activate latent TGF-beta1 and that this is regulated by 1alpha,25(OH)2D3. To do
      this, we examined the ability of matrix vesicle extracts to activate small latent
      rhTGF-beta1. In addition, enzymes previously determined to be present in matrix
      vesicles were screened for their ability to activate small latent rhTGF-beta1.
      Recombinant human matrix metalloproteinase 2 (rhMMP-2; 72 kDa gelatinase), rhMMP
      3 (stromelysin 1), purified human plasminogen, and purified urokinase
      (plasminogen activator) were each tested at varying concentrations. To assess the
      role of cell maturation, we used a cell culture model in which chondrocytes are
      derived from two distinct zones of rat costochondral cartilage, the resting zone
      and the growth zone. Matrix vesicles were isolated from these cultures and then
      tested. The results showed that extracts of matrix vesicles produced by both
      growth zone and resting zone chondrocytes were able to activate small latent
      rhTGF-beta1. The effects were dose and time dependent, with greater activity
      being found in extracts of matrix vesicles from the growth zone chondrocyte
      cultures. Only rhMMP-3 was able to activate small latent rhTGF-beta1, indicating
      that stromelysin-1, but not MMP-2, plasminogen, or urokinase, was involved. As
      observed in the extracts, the effect of rhMMP-3 was time and dose dependent. When
      anti-MMP-3 antibody was added to matrix vesicle extracts from both cell types,
      activation of small latent rhTGF-beta1 was dose-dependently blocked. Neither
      1alpha,25(OH)2D3 nor 24R,25(OH)2D3 had a direct effect on activation of small
      latent rhTGF-beta1 by the extracts. However, when intact matrix vesicles were
      treated with 1alpha,25(OH)2D3, their ability to activate small latent rhTGF-beta1
      was increased. Inhibition of phospholipase A2 with quinacrine blocked the
      1alpha,25(OH)2D3-dependent effect. These results suggest that the ability of
      1alpha,25(OH)2D3-treated matrix vesicles to activate small latent TGF-beta1 is
      via action of the secosteroid on the matrix vesicle membrane, not on the enzymes
      responsible for activating latent TGF-beta1. Because matrix vesicles isolated
      from growth zone chondrocytes have been shown to contain increased phospholipase
      A2 activity after treatment with 1alpha,25(OH)2D3, it is likely that this
      secosteroid promotes loss of membrane integrity through phospholipase A2
      dependent formation of lysophospholipids, resulting in the release of MMP-3 into
      the matrix, where latent TGF-beta1 is stored. Taken together, the results of the
      current study show that matrix vesicles produced by growth plate chondrocytes
      contain MMP-3, that this enzyme is at least partially responsible for activation
      of small latent TGF-beta1 in the matrix, and that 1alpha,25(OH)2D3 regulates MMP
      release from matrix vesicles.

PMID- 11450705
TI  - Does body size account for gender differences in femur bone density and geometry?
AB  - The extent to which greater bone strength in men is caused by proportionately
      greater bone mass versus bigger bone size is not clear, primarily because the
      larger overall body size of men has made direct comparisons of skeletal measures
      difficult. We examined gender differences in femur neck (FN) areal bone mineral
      density (BMD) values collected from 5,623 non-Hispanic whites aged 20+ years in
      the third National Health and Nutrition Examination Survey (NHANES III, 1988
      1994) before and after correction for measured height and weight. We supplemented
      the conventional areal BMD data (Hologic QDR 1000) with measurements of areal BMD
      and geometric properties (subperiosteal width, section modulus, and cortical
      thickness) made at narrow "cross-sectional" regions traversing the FN and the
      proximal shaft using a structural analysis program. Before body size adjustment,
      men had significantly higher values than women for all variables at the three
      measurement sites (p < 0.0001). Adjustment for body size reduced the differences
      between the sexes for all variables but had a greater effect on BMD (1-8% higher
      in men) than on geometry (5-17% higher in men). When examined by age, the sex
      discrepancy was significantly greater in the older group for all variables except
      subperiosteal widths. We conclude that although body size difference may account
      for most of the areal BMD difference between men and women, male bones are still
      bigger in ways that suggest greater bone strength. These differences may
      contribute importantly to lower fracture risk in men.

PMID- 11450706
TI  - Continuous parathyroid hormone and estrogen administration increases vertebral
      cancellous bone volume and cortical width in the estrogen-deficient rat.
AB  - Generally, it is believed that intermittent administration of parathyroid hormone
      (PTH) has an anabolic effect on the skeleton, whereas continuous administration
      is catabolic. However, there is evidence that continuous exposure to PTH may have
      an anabolic effect, for example, in patients with mild primary
      hyperparathyroidism (PHPT). The possibility of delivering PTH continuously may
      have important implications for the treatment of osteoporosis. Furthermore,
      estrogen treatment may be useful in the medical management of PHPT. Therefore, we
      examined the skeletal effects of continuous administration of PTH, with or
      without estrogen, in the estrogen-deficient rat with established osteopenia.
      Forty 7-month-old SD rats were divided into four ovariectomy (OVX) groups and one
      sham-operated group. Eight weeks post-OVX, three groups received subcutaneous
      implants of Alzet mini pumps loaded with PTH(1-34) (30 microg/kg per day), 17beta
      estradiol (10 microg/kg per day) pellet, or both PTH and 17beta-estradiol
      separately for 4 weeks. OVX and sham control groups were given the mini pumps
      loaded with vehicle. Two doses of calcein (10 mg/kg) were given subcutaneously to
      all rats 2 days and 8 days before death. Histomorphometry was performed on
      cancellous and cortical bone of the fourth lumbar vertebra. At 3 months, post-OVX
      rats displayed bone loss with high bone turnover. Estrogen reversed OVX-mediated
      high turnover without restoring cancellous bone volume (BV/TV). PTH infusion
      further increased bone turnover and partially restored BV/TV. However, PTH
      infusion increased cortical porosity. Estrogen inhibited PTH-mediated cancellous
      bone resorption and substantially increased BV/TV above sham control. The
      combined treatment was associated with a significant increase in peritrabecular
      fibrosis and woven bone formation. The combined treatment of PTH infusion and
      estrogen replacement enhanced cortical width but estrogen did not prevent the PTH
      induced cortical tunneling. We conclude that continuous administration of PTH and
      estrogen increases cortical porosity but has substantial beneficial effects on
      vertebral cancellous bone volume and cortical width in OVX rats.

PMID- 11450707
TI  - Distribution of intracortical porosity in human midfemoral cortex by age and
      gender.
AB  - The purpose of this study was to describe the age-specific distribution of
      midfemoral intracortical porosity throughout the cortical width in males and
      females. Microradiography and an automated image analysis system were used to
      study midfemoral cortical bone specimens from 163 white people, including 77
      males and 86 females, in a recent anthropological collection covering a broad age
      range. In each specimen, porosity (percentage of the cortical bone area occupied
      by pores), pore number, and pore size were measured throughout the entire cortex
      and in three cortical subregions of equal width labeled the periosteal,
      midcortical, and endosteal subregions. For each gender, relationships linking age
      to porosity, pore number, and mean pore size were assessed using regression
      analysis. In addition, age- and site-related changes in these three variables
      were tested for significance using two-way analysis of variance (ANOVA). Age
      explained 52% of the porosity variance in females and 13.5% in males. In each
      gender, there were significant age- and site-related differences in porosity,
      pore number, and pore size. In adults aged 60 years or younger, both pore size
      and pore number increased with increasing age, whereas in adults older than 60
      years, pore size continued to increase but pore number decreased. In males, the
      age-related changes in pore size and pore number were proportionally similar in
      the three cortical subregions. In females, in contrast, the changes predominated
      in the endosteal subregion and resulted in significant cortical thinning.

PMID- 11450708
TI  - Intracapsular hip fracture and the region-specific loss of cortical bone:
      analysis by peripheral quantitative computed tomography.
AB  - Generalized bone loss within the femoral neck accounts for only 15% of the
      increase in intracapsular hip fracture risk between the ages of 60 and 80 years.
      Conventional histology has shown that there is no difference in cancellous bone
      area between cases of intracapsular fracture and age and sex-matched controls.
      Rather, a loss of cortical bone thickness and increased porosity is the key
      feature with the greatest change occurring in those regions maximally loaded
      during a fall (the inferoanterior [IA] to superoposterior [SP] axis). We have now
      reexamined this finding using peripheral quantitative computed tomography (pQCT)
      to analyze cortical and cancellous bone areas, density, and mass in a different
      set of ex vivo biopsy specimens from cases of intracapsular hip fracture (female,
      n = 16, aged 69-92 years) and postmortem specimens (female, n = 15, aged 58-95
      years; male, n = 11, aged 56-86 years). Within-neck location was standardized by
      using locations at which the ratio of maximum to minimum external diameters was
      1.4 and at more proximal locations. Cortical widths were analyzed using 72 radial
      profiles from the center of area of each of the gray level images using a full
      width/half-maximum algorithm. In both male and female controls, cancellous bone
      mass increased toward the femoral head and the rate of change was gender
      independent. Cancellous bone mass was similar in cases and controls at all
      locations. Overall, cortical bone mass was significantly lower in the fracture
      cases (by 25%; p < 0.001) because of significant reductions in both estimated
      cortical area and density. These differences persisted at locations that are more
      proximal. The mean cortical width in the cases was significantly lower in the IA
      (22.2%;p = 0.002) and inferior regions (19%;p < 0.001). The SP region was the
      thinnest in both cases and controls. These data confirm that a key feature in the
      etiology of intracapsular hip fracture is the site-specific loss of cortical
      bone, which is concentrated in those regions maximally loaded during a fall on
      the greater trochanter. An important implication of this work is that the
      pathogenesis of bone loss leading to hip fracture must be by a mechanism that
      varies in its effect according to location within the femoral neck Key candidate
      mechanisms would include those involving locally reduced mechanical loading. This
      study also suggests that the development of noninvasive methodologies for
      analyzing the thickness and estimated densities of critical cortical regions of
      the femoral neck could improve detection of those at risk of hip fracture.

PMID- 11450709
TI  - Bone turnover and density in obese premenopausal women during moderate weight
      loss and calcium supplementation.
AB  - Bone turnover is increased during weight loss in postmenopausal women and can be
      suppressed with calcium supplementation. In this study, we assessed the influence
      of energy restriction with and without calcium supplementation (1 g/day) in
      premenopausal women. Thirty-eight obese premenopausal women (body mass index
      [BMI] of 35.0 +/- 3.9 kg/m2) completed a 6-month study of either moderate weight
      loss or weight maintenance. During weight loss, women were randomly assigned to
      either a calcium supplementation (n = 14) or placebo group (n = 14) and lost 7.5
      +/- 2.5% of their body weight. The control group of women (n = 10) maintained
      their body weight. Total body and lumbar bone mineral density (LBMD) and content
      were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after
      weight loss. Throughout the study, blood and urine samples were collected to
      measure bone turnover markers and hormones. During moderate energy restriction,
      dietary calcium intake decreased (p < 0.05) and the bone resorption marker
      deoxypyridinoline (DPD) increased slightly (p < or = 0.05) without evidence of
      bone loss. Calcium supplementation during weight loss tended to increase lumbar
      BMD by 1.7% (p = 0.05) compared with the placebo or weight maintenance groups. In
      contrast to our previous findings in postmenopausal women, premenopausal obese
      women who consume a low calcium diet do not lose bone over a 6-month period,
      whether their weight is stable or decreasing moderately.

PMID- 11450710
TI  - Increased body weight and decreased radial cross-sectional dimensions in girls
      with forearm fractures.
AB  - A large number of children sustain fractures after relatively minor trauma and
      several investigators have associated these fractures to a deficient accumulation
      of bone during growth. This study was conducted to better characterize the
      skeletal phenotype associated with low-energy impact fractures of the forearm in
      girls. The densities of cancellous, cortical, and integral bone and the cross
      sectional area were measured in the radius of 100 healthy white girls (aged 4-15
      years) using computed tomography (CT); 50 girls had never fractured and 50 girls
      had sustained a forearm fracture within the previous month. Fractured and
      nonfractured groups were matched for age, height, weight, and Tanner stage of
      sexual development. Compared with controls, girls with fractures had, on average,
      8% smaller cross-sectional area at the distal radius (1.82 +/- 0.50 cm2 vs. 1.97
      +/- 0.42 cm2; p < 0.0001) but similar cancellous, integral, and cortical bone
      densities. Neither radial length nor the amount of fat or muscle at the midshaft
      of the radius differed between girls with and without fractures. Both study
      subjects and matched controls were overweight. Although mean height was at the
      50th percentile, mean weight was at the 90th percentile for age-adjusted normal
      values. Girls who sustain forearm fractures after minor trauma have small cross
      sectional dimensions of the radius and tend to be overweight. The smaller cross
      sectional area confers a biomechanical disadvantage that, coupled with the
      greater body weight, increases the vulnerability to fracture after a fall.

PMID- 11450711
TI  - Race and sex effects on the association between muscle strength, soft tissue, and
      bone mineral density in healthy elders: the Health, Aging, and Body Composition
      Study.
AB  - Two factors generally reported to influence bone density are body composition and
      muscle strength. However, it is unclear if these relationships are consistent
      across race and sex, especially in older persons. If differences do exist by race
      and/or sex, then strategies to maintain bone mass or minimize bone loss in older
      adults may need to be modified accordingly. Therefore, we examined the
      independent effects of bone mineral-free lean mass (LM), fat mass (FM), and
      muscle strength on regional and whole body bone mineral density (BMD) in a cohort
      of 2,619 well-functioning older adults participating in the Health, Aging, and
      Body Composition (Health ABC) Study with complete measures. Participants included
      738 white women, 599 black women, 827 white men, and 455 black men aged 70-79
      years. BMD (g/cm2) of the femoral neck, whole body, upper and lower limb, and
      whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy
      X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were
      determined by dynamometry. In analyses stratified by race and sex and adjusted
      for a number of confounders, LM was a significant (p < 0.001) determinant of BMD,
      except in white women for the lower limb and whole body. In women, FM also was an
      independent contributor to BMD at the femoral neck, and both FM and muscle
      strength contributed to limb BMD. The following were the respective beta-weights
      (regression coefficients for standardized data, Std beta) and percent difference
      in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-5.9%; lower limb,
      0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7%; and upper limb
      (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral
      apparent density [BMAD]) or body size BMD/height) diminished the importance of
      LM, and the contributory effect of FM became more pronounced. These results
      indicate that LM and FM were associated with bone mineral depending on the bone
      site and bone index used. Where differences did occur, they were primarily by sex
      not race. To preserve BMD, maintaining or increasing LM in the elderly would
      appear to be an appropriate strategy, regardless of race or sex.

PMID- 11450712
TI  - Ultrasonic backscatter and transmission parameters at the os calcis in
      postmenopausal osteoporosis.
AB  - Ultrasound technology has emerged as a new tool in the assessment of
      osteoporosis. Ultrasound parameters usually are measured in transmission; there
      is a potential for the analysis of backscattered signals to provide information
      on bone microarchitecture. The aim of this study was to explore a new
      technological development of the method, adding backscatter coefficient to
      transmission parameters, and to examine the appropriate thresholds to identify
      postmenopausal osteoporotic women. We examined 210 postmenopausal women
      (including 60 with osteoporotic fractures) and 30 healthy premenopausal controls.
      They had lumbar spine and hip bone mineral density (BMD) measurement and
      quantitative ultrasound (QUS) evaluation at the os calcis, measured in
      transmission (broadband ultrasound attenuation [BUA], speed of sound [SOS], ratio
      of transit time [dt] to BUA [dt/BUA], and "strength" index [STI]) and reflexion
      (broadband ultrasound backscattering [BUB]). The standardized CVs (sCVs) were
      between 2.27 % and 3.40 % for QUS measured in transmission and 4.41% for BUB. The
      odds ratio (OR) for fracture discrimination adjusted for age was 2.77 for hip BMD
      and between 1.6 and 2.9 for QUS. After adjustment for hip BMD, ORs were still
      highly significant for SOS, STI, and dt/BUA. According to hip BMD T score,
      prevalence of osteoporosis in our population was 39%. To detect the same
      prevalence, T scores ranged between -0.95 and -1.42 for QUS. QUS parameters have
      adequate ability to discriminate osteoporotic patients from controls. The World
      Health Organization (WHO) threshold for diagnosis of osteoporosis does not apply
      to this technology. The clinical utility of BUB at the os calcis, in addition to
      usual ultrasound parameters, is not yet proven. However, BUB evaluation, which
      does not require two transducers and may be implemented in conventional
      reflection mode systems, warrants further studies.

PMID- 11450713
TI  - Soy intake and the maintenance of peak bone mass in Hong Kong Chinese women.
AB  - Our previous study on bone health among premenopausal women showed that bone mass
      consolidation is attained by the early 30s, and small loss of spinal bone mineral
      density (SBMD) occurs soon after peak bone mass attainment. Recent interest has
      been shown in the potential beneficial effects of phytoestrogens on bone health.
      However, data are lacking, particularly in Asian women. This study aims to
      investigate the effect of soy isoflavones intake on the maintenance of peak bone
      mass in a cohort of 132 women aged 30-40 years who were followed up for 3 years.
      Baseline measurements of SBMD (L2-L4) were obtained using dual-energy X-ray
      densitometry, and dietary intake of soy foods and other key nutrients, including
      dietary calcium, were obtained through a quantitative food frequency method.
      Information on body measurements; physical activity (PA), weight-bearing activity
      in particular; age of menarche; and number of pregnancies were obtained at
      baseline. Repeated measurements of SBMD were obtained yearly for a further 3
      years with an average follow-up time of 38 months. Analyses were performed on 116
      subjects with at least three SBMD measurements (at baseline, 3-year follow-up,
      and at least one measurement during follow-up). The individual SBMD regression
      slope was computed for each of the subjects. Soy isoflavones consumption was
      categorized as quartiles of intake. We observed a significant difference in the
      SBMD individual regression slopes between women belonging to the fourth and first
      soy isoflavones intake quartiles. The positive effect of soy isoflavones on SBMD
      remained after adjusting for age and body size (height, weight, and bone area).
      Multiple linear regression analysis including the other known covariates (lean
      body mass, PA, energy adjusted calcium, and follow-up time) showed that soy
      isoflavones, together with these variables, accounted for 24% of the variances of
      the SBMD individual regression slope. This longitudinal study shows that soy
      intake had a significant effect on the maintenance of SBMD in women aged 30-40
      years. The effects of phytoestrogens on bone health should be explored further in
      a population with habitual dietary soy but low calcium intake.

PMID- 11450714
TI  - The Achilles' heel of exercise-induced bone mass increments: cessation of
      exercise.

PMID- 11450715
TI  - Bone microarchitecture in osteoporotic men: universal or corticosteroid
      dependent?

PMID- 11450716
TI  - Confocal scanning laser Doppler flowmetry in retinovascular disease.

PMID- 11450717
TI  - A prospective evaluation of the Heidelberg retina flowmeter in diagnosing
      ischaemia following branch retinal vein occlusion: a masked, controlled
      comparison with fluorescein angiography.
AB  - PURPOSE: To evaluate the use of the Heidelberg retina flowmeter (HRF) in
      diagnosing retinal ischaemia following macular branch retinal vein occlusion.
      METHODS: Ten patients with ischaemic macular branch retinal vein occlusion, as
      determined by strict fluorescein angiographic criteria, were examined with the
      HRF. Blood flow, blood volume and blood velocity characteristics from areas of
      ischaemic and non-ischaemic retina were recorded and the results between the
      normal and ischaemic areas of retina compared with paired t-test analysis. Ten
      healthy volunteers were similarly examined and acted as a control group. RESULTS:
      Compared with normal retina the HRF recorded a statistically significant
      reduction in blood flow within the ischaemic retina in 7 of the 10 study
      patients. In 2 patients the HRF actually recorded a statistically significant
      increase in blood flow in the area of ischaemic retina; there was no significant
      difference in the blood flow recorded in the normal and ischaemic retina in the
      remaining patient. HRF examination of the control group revealed a significant
      difference in the blood flow between two areas of apparently normal retina in 3
      of the 10 volunteers. CONCLUSION: The HRF is not a reliable tool for diagnosing
      retinal ischaemia following branch retinal vein occlusion. Our results may
      suggest that the HRF blood flow recordings are not derived from the retinal
      circulation alone, but represent the cumulative blood flow through the combined
      circulations of the retina and choriocapillaris.

PMID- 11450718
TI  - Benign idiopathic haemorrhagic retinopathy.
AB  - PURPOSE: To describe a new condition characterised by an unusual unilateral
      idiopathic haemorrhagic retinopathy. METHODS: A review is presented of patient
      histories from 5 patients with acute-onset unilateral idiopathic haemorrhagic
      retinopathy, including results of ophthalmological, haematological and
      fluorescein angiographic examinations. RESULTS: All patients had an extensive
      deep blot haemorrhagic retinopathy without significant vascular signs or abnormal
      optic discs. In 4 cases the haemorrhage was sufficiently severe to break through
      into the vitreous. Fluorescein angiography demonstrated normal arteriovenous
      flow, without capillary non-perfusion, vessel or disc leakage. Disc swelling,
      macular oedema and cotton wool spots were not seen at any stage in these
      patients. All patients recovered the visual acuity in the affected eye by 4
      months. Systemic examination in all cases was unremarkable. CONCLUSION: This
      distinct and rare form of retinopathy is important to define since it has a good
      prognosis without treatment.

PMID- 11450719
TI  - Trabeculectomy outcomes in advanced glaucoma in Nigeria.
AB  - BACKGROUND: Trabeculectomy remains the mainstay of therapy for advanced glaucoma
      in Nigeria due to the unavailability and expense of topical therapy. Little is
      known of the medium- to long-term outcomes of trabeculectomy in West Africa.
      Purpose To retrospectively assess outcomes, in terms of lowering of the
      intraocular pressure and preserving the visual acuity, and the safety of
      trabeculectomy in patients with advanced glaucoma in Nigeria. METHODS: A
      retrospective case-note search was carried out from operating theatre records in
      a private hospital at Lagos, Nigeria from 1989 to 1997. Patients undergoing
      primary trabeculectomy with a minimum follow-up of 6 months were included in the
      study. Visiting consultants and registrars from the UK performed the surgery.
      Descriptive statistics and life-table analysis were applied to the data. RESULTS:
      One hundred and forty-two eyes of 100 patients were included in the study. When
      the criteria for success were an intraocular pressure (IOP) of less than 22 mmHg,
      30% reduction from pre-operative levels and a decrease in visual acuity of less
      than 3 Snellen chart lines, then by life-table analysis success rates were 85%,
      82% and 71% at the 1, 2 and 5 year post-operative intervals respectively. Success
      rates were lower if an IOP of less than 16 mmHg was taken as one of the criteria
      (65%, 61% and 46% at the 1, 2 and 5 year intervals, respectively). CONCLUSIONS:
      Trabeculectomy without antimetabolite use appears to be an effective way to lower
      the IOP of advanced glaucoma patients in Nigeria to less than 22 mmHg but not to
      less than 16 mmHg. The procedure, in experienced hands, is relatively safe with
      few major complications.

PMID- 11450720
TI  - Evaluation of a disposable prism for applanation tonometry.
AB  - BACKGROUND: Recently the Medical Devices Agency recommended that 'ophthalmic
      devices that touch the surface of the eye should be restricted to single use'.
      AIM: To evaluate one such device: a disposable tonometer prism for routine
      applanation tonometry. METHODS: The intraocular pressure (IOP) of 100 consecutive
      patients from a general eye clinic (197 eyes) was measured with both a disposable
      and the standard Goldmann tonometer (Goldmann). The level of agreement between
      the two methods of clinical measurement was assessed and the sensitivity and
      specificity of the disposable prism in detecting clinically significant raised
      IOP estimated. RESULTS: The mean difference in IOP measured by the two different
      prisms was 0.44 mmHg with a standard deviation (SD) of 1.54. The mean IOP for the
      disposable prism was 19.51 mmHg (SD 6.53 mmHg). The mean IOP for the standard
      Goldmann tonometer prism was 19.07 mmHg (SD 6.64 mmHg). The sensitivity to detect
      IOP > 21 mmHg was 95.9% (95% confidence interval (CI): 86.0-99.5%) and the
      specificity of 93.9% (95% CI: 88.8-97.2%). It gave a positive predictive value of
      83.9% (95% CI: 71.7-92.4%). CONCLUSION: There was close agreement between the IOP
      measurements obtained by the disposable tonometer prism and the Goldmann device
      for high and low pressures. If replicated, the high sensitivity and specificity
      would justify its use in screening.

PMID- 11450721
TI  - What optic disc parameters are most accurately assessed using the direct
      ophthalmoscope?
AB  - PURPOSE: It has been suggested that over-reliance on the cup-to-disc ratio is a
      major factor in the misinterpretation of the optic disc. In spite of this
      optometrist assessment of the optic disc tends to be restricted to measurement of
      the cup-to-disc ratio and cup depth only. Would interpretation of the disc
      improve if optometrists were to evaluate other parameters? The aim of this study
      was to evaluate the accuracy of optometrist assessment of nine parameters of the
      optic nerve head using direct ophthalmoscopy. METHODS: Eight optometrists
      evaluated nine parameters of the optic nerve head (vertical disc diameter,
      vertical cup-to-disc ratio, neuroretinal rim configuration, cup shape,
      neuroretinal rim colour, vessel path, presence/ absence of haemorrhage, extent
      and location of peripapillary atrophy and classification of health status of the
      disc) in 50 eyes of 50 patients using direct ophthalmoscopy. Intensive training
      in optic nerve head assessment was given prior to assessing the patients.
      Criteria for evaluation were discussed. The 'gold standard' reference was the
      classification of the parameters by a consultant ophthalmologist with a special
      interest in glaucoma. RESULTS: Interobserver agreement for vertical cup-to-disc
      ratio was almost perfect (mean weighted kappa 0.84). Agreement for neuroretinal
      rim configuration, cup shape, haemorrhage and final classification of the disc
      was good (mean kappa 0.62-0.67). There was moderate agreement for vessel
      configuration (mean kappa 0.53). For assessment of peripapillary atrophy, disc
      size and neuroretinal rim colour, agreement was fair (mean kappa 0.22-0.34).
      CONCLUSIONS: Accuracy of assessment was greatest for vertical cup-to-disc ratio,
      neuroretinal rim configuration and cup shape. Improved agreement has been
      demonstrated for the final classification of the disc compared with previous
      reports. The combination of training and assessment of additional disc parameters
      appears to improve interpretation of the optic nerve head by optometrists.

PMID- 11450722
TI  - 11-0 Mersilene alone as a single running suture in corneal grafts.
AB  - PURPOSE: To study the safety and long-term stability of 11-0 Mersilene when used
      alone as a single running suture in corneal grafts. METHODS: Seventeen eyes on
      which corneal transplants were performed with 11-0 Mersilene alone as a single
      running suture between October 1992 and April 1998 were entered into this study.
      Post-operative data were collected retrospectively on a standardised form. Mean
      age of patients at the time of surgery was 49.7 years. Pre-operative diagnoses
      were keratoconus (8 eyes), Fuchs' corneal dystrophy (6 eyes), megalocornea (1
      eye), bullous keratopathy (1 eye) and irregular astigmatism following penetrating
      corneal injury (1 eye). Mean follow-up was 54.1 months, and ranged between 24 and
      91 months. RESULTS: Fourteen eyes (82%) achieved visual acuities of 6/18 or
      better. Post-keratoplasty astigmatism was < or = 5D in 14 eyes (82%). Sutures
      were left intact in 9 eyes for a mean period of 51.1 months (24-91 months).
      Complications included wound leak (3 cases), elevated edge (1 case), high
      intraocular pressure (1 case), sterile infiltrates (1 case) and early rejection
      (1 case). CONCLUSION: 11-0 Mersilene alone can be effectively used as a single
      running suture in corneal grafts. These sutures can safely be left intact for a
      long period due to Mersilene's non-biodegradable nature.

PMID- 11450723
TI  - Pterygium excision and conjunctival mini-autograft: preliminary report.
AB  - PURPOSE: Pterygium excision is often followed by recurrence that may be more
      severe than the initial lesion. This study evaluated the efficacy of conjunctival
      mini-autograft following surgical excision of pterygium. METHODS: Eight patients
      underwent pterygium excision with a conjunctival mini-autograft. All patients had
      decreased visual acuity secondary to involvement of the central cornea by the
      pterygium. Following the excision, dissection of a conjunctival mini-autograft
      was performed. The mini-autograft was then transposed to the area of excision and
      secured in place with interrupted Vicryl and a few nylon sutures. Follow-up
      periods ranged from 5 to 9 years. RESULTS: All eyes healed with no post-operative
      complications and no recurrences of the pterygium in any patient up to a maximum
      follow-up period of 9 years 10 months. CONCLUSION: Conjunctival mini-autograft
      with excision of the pterygium is an effective procedure for the surgical
      management of pterygium.

PMID- 11450724
TI  - The treatment of severe trachomatous dry eye with canalicular silicone plugs.
AB  - PURPOSE: To evaluate the effects of temporary canalicular occlusion with silicone
      plugs on trachomatous dry eye patients who were on maximal tolerable medical
      therapy. METHODS: Forty-four trachomatous dry eye patients who had Schirmer
      testing with topical anaesthetic measuring 5 mm or less and a tear film break-up
      time of 5 s or less were included. After the lacrimal efficiency test with
      dissolvable collagen punctal plugs, silicone canalicular plugs were placed in 22
      trachomatous dry eye patients. The other 22 patients in the untreated control
      group were allowed to continue their medical therapy. Pretreatment and post
      treatment evaluations included subjective patient assessment, rose Bengal and
      fluorescein staining, tear film break-up time, Schirmer testing, conjunctival
      impression cytology and goblet cell counting. RESULTS: Six months after plug
      placement, 18 eyes (82%) of 22 patients had subjective improvement and all these
      patients successfully wore plugs for at least 6 months. There were statistically
      significant differences between the pretreatment and post-treatment test results
      including rose Bengal and fluorescein staining scores, tear film break-up times
      and Schirmer testing measurements. Impression cytology showed improvement of
      squamous metaplasia in 17 eyes (77%). Eight of the patients (36%) were able to
      decrease dependency on topical therapy. Ten of the patients (45%) completely
      stopped using artificial tears. There were statistically significant differences
      between the two groups in the total symptom scores, staining scores, tear film
      break-up time, Schirmer testing, impression cytology scores and goblet cell
      counts. CONCLUSION: In cases where topical tear supplementation is insufficient
      to relieve the signs and symptoms of severe dry eye and the lacrimal puncta have
      not already been closed by the trachomatous cicatrising process, occlusion of the
      canaliculi may be useful to prevent drainage of both natural and artificial
      tears. Canalicular occlusion improves the objective signs and subjective symptoms
      and may significantly decrease dependency on tear supplements in selected
      patients.

PMID- 11450725
TI  - Refractive changes following Nd:YAG capsulotomy.
AB  - PURPOSE: To investigate the effect of Nd:YAG capsulotomy on refractive changes
      and the need for a post-capsulotomy refraction. METHODS: Forty-two eyes with
      uncomplicated phacoemulsification and implant (AMO@Phacoflex II) were included.
      Autorefraction and subjective refraction were performed to get the best visual
      acuity before and after Nd:YAG capsulotomy. RESULTS: The spherical equivalent
      before the Nd:YAG capsulotomy was -0.61 +/- 0.90 and after the capsulotomy, -0.57
      +/- 0.84. Using the paired Student's t-test there was no significant difference
      in the refraction following Nd:YAG capsulotomy. CONCLUSION: Routine refraction
      following Nd:YAG capsulotomy in patients who have had uncomplicated
      phacoemulsification using AMO@Phacoflex II intraocular lenses is not necessary.

PMID- 11450726
TI  - 'One-stop' cataract surgery: the Bristol Eye Hospital experience 1997-1999.
AB  - PURPOSE: To evaluate patient satisfaction with and effectiveness of the 'one
      stop' cataract service at the Bristol Eye Hospital. METHODS: One hundred and
      ninety patients referred with a view to cataract surgery were selected to attend
      24 'one-stop' clinics between February 1997 and August 1999. Patients had initial
      assessment in the morning with suitable cases undergoing surgery during the
      afternoon. Forty 'one-stop' patients and 40 patients undergoing traditional
      surgery (three separate visits: initial clinic, pre-assessment and surgery) were
      surveyed by a questionnaire to determine their satisfaction with the service.
      RESULTS: One hundred and fifty-six of 190 (82.1%) patients invited to one-stop
      clinics underwent surgery the same day. Questionnaires were returned by 72
      patients (35 'one-stop' and 37 control patients). Twenty-eight (80%) 'one stop'
      patients were 'very satisfied' and 7 (20%) were 'satisfied' with the time allowed
      to decide upon undergoing surgery, compared with 21 (57%) and 16 (43%)
      respectively in the control group (p = 0.06, chi-square, not significant).
      Overall satisfaction with the service was similar between the groups, with 33
      (94%) of 'one-stop' and 35 (95%) of control patients considering the service
      'very good'. CONCLUSIONS: There is a high level of patient satisfaction with a
      'one-stop' cataract service which reduces hospital attendance from three visits
      to one. Potential problems include wasted theatre space when there is a shortfall
      of suitable cases on the day.

PMID- 11450727
TI  - Conjunctival myxoma, Zollinger-Ellison syndrome and abnormal thickening of the
      inter-atrial septum: a case report and review of the literature.
AB  - PURPOSE: To report a 36-year-old man with a slowly growing painless bulbar
      conjunctival mass. RESULTS: Following excision of the lesion, histological
      examination was performed and a diagnosis of myxoma was made. A cardiac echogram
      showed thickening of the interatrial septum. Seventeen years previously he had
      had Zollinger Ellison syndrome due to gastrinoma of the pancreas which was
      treated by surgical removal. A review of the literature shows ocular myxomas may
      be associated with endocrine abnormalities such as Cushing's syndrome,
      acromegaly, sexual precocity and cardiac myxoma. CONCLUSION: In this case we
      report a novel association of conjunctival myxoma with Zollinger-Ellison syndrome
      and inter-atrial septal thickening.

PMID- 11450728
TI  - Serial STIR magnetic resonance imaging correlates with clinical score of activity
      in thyroid disease.
AB  - PURPOSE: To assess the correlation between inflammatory activity in extraocular
      muscles measured with serial short tau inversion recovery (STIR) sequence
      magnetic resonance imaging (MRI) scans and clinical disease activity in thyroid
      eye disease. METHODS: In this retrospective study, 22 patients with thyroid eye
      disease who had undergone serial MRI scans using the STIR sequence were assessed.
      The signal intensity ratio (SIR) of the most inflamed extraocular muscle was
      compared with the Mourits score (a clinical measure of thyroid eye disease
      activity). RESULTS: The SIR value has previously been shown to correlate with
      clinical activity of thyroid eye disease. In a particular patient the SIR value
      increases in proportion with the clinical features of the disease as assessed by
      the Mourits rating system. When the change in STIR sequence MRI is compared with
      the change in Mourits score rating for a given patient the correlation is highly
      significant (p < 0.001). CONCLUSIONS: This study confirms that serial STIR
      sequence MRI scans correlate with clinical disease activity. Inflammatory
      activity in the most inflamed muscle (as measured by SIR) reflects overall
      disease activity. SIR values obtained from MRI scans provide a useful measure of
      disease activity and may help in the monitoring and treatment of this condition.

PMID- 11450729
TI  - Increased numbers of caveolae in retinal endothelium and pericytes in
      hypertensive diabetic rats.
AB  - PURPOSE: Long-term clinical studies have now shown that tight control of blood
      pressure in type 2 diabetes reduces the risk of diabetes-related death and common
      diabetic complications, including diabetic retinopathy. However, the mechanisms
      by which hypertension enhances diabetic microvascular disease, especially
      diabetic retinopathy, are poorly understood. We developed an experimental model
      of hypertension in diabetic rats and studied the early ultrastructural changes in
      retinal capillaries under these conditions. METHODS: Hypertension was induced in
      diabetic BioBreeding (BB) rats by unilateral nephrectomy, weekly subcutaneous
      mineralocorticoid and 0.9% oral saline. Serial blood pressures and
      ultrastructural features of retinal capillaries were recorded in four groups:
      normotensive Wistar rats, normotensive diabetic rats, hypertensive Wistar rats
      and hypertensive diabetic rats. RESULTS: A significant and sustained increase in
      systolic blood pressure occurred in both groups of nephrectomised rats. There was
      a significant increase in the number of caveolae (i) in both pericytes and
      endothelial cells in animals with hypertension and diabetes together compared
      with all other groups and (ii) in pericytes in animals with diabetes alone. The
      number of direct contacts between pericytes and endothelial cells was reduced in
      diabetic and hypertensive diabetic animals. Hypertension and diabetes had an
      interactive effect in producing retinal capillary basement membrane thickening.
      CONCLUSIONS: In the BB rat hypertension and diabetes have an interactive effect
      in increasing the number of caveolae in both endothelial cells and pericytes. We
      speculate that this may be a reflection of changes in calcium and nitric oxide
      metabolism in these animals.

PMID- 11450730
TI  - Influence of subconjunctival steroid injection on blood glucose profile in
      diabetic rats.
AB  - PURPOSE: The influence of subconjunctival steroid injection on blood glucose
      concentration was investigated in rats with streptozotocin (STZ)-induced
      diabetes. METHODS: Adult male Wistar rats with STZ-induced diabetes (n = 10) and
      normal controls (n = 10) received subconjunctival injections of 0.1 ml of 0.4%
      dexamethasone or saline. Blood glucose concentrations were measured before and 3,
      6, 12, 18 and 24 h after treatment. RESULTS: In the STZ group, subconjunctival
      injection of steroids (p = 0.0013) or saline (p = 0.0037) significantly increased
      the blood glucose level 3 h after treatment. In the control group, the blood
      glucose concentration was not elevated by subconjunctival injection. In both STZ
      and control groups, the blood glucose concentration was significantly higher
      after steroid injection than after saline injection throughout the 24 h study
      period. CONCLUSIONS: Subconjunctival steroid injection induced a significant
      blood glucose increase in both diabetic and control rats. For diabetic rats, the
      subconjunctival injection itself constituted stress that resulted in glucose
      elevation.

PMID- 11450731
TI  - Pigmented paravenous retinochoroidal atrophy: evidence of progression to macular
      involvement in a family with a 42-year history.

PMID- 11450732
TI  - Pupillary block after silicone oil implantation in a phakic eye.

PMID- 11450733
TI  - Lens deposits associated with RIMSO-50 (dimethylsulphoxide).

PMID- 11450734
TI  - Corneal burn secondary to amyl nitrite.

PMID- 11450735
TI  - Retinal detachment associated with macular hole in a patient with high myopic
      Usher's syndrome.

PMID- 11450736
TI  - Indocyanine green angiographic findings in serpiginous choroidopathy: evidence of
      a widespread choriocapillaris defect of the peripapillary area and posterior
      pole.

PMID- 11450737
TI  - Visual recovery following intraocular infiltration of gentamicin.

PMID- 11450738
TI  - Concentric annular macular dystrophy.

PMID- 11450739
TI  - An unusual cause of orbital apex syndrome.

PMID- 11450740
TI  - Orbital apex syndrome as a presenting sign of maxillary sinus carcinoma.

PMID- 11450741
TI  - Clear tectonic penetrating graft using glycerine-preserved donor cornea.

PMID- 11450742
TI  - Bilateral poliosis and granulomatous anterior uveitis associated with latanoprost
      use and apparent hypotrichosis on its withdrawal.

PMID- 11450743
TI  - Intralenticular abscess caused by Stenotrophomonas maltophilia.

PMID- 11450744
TI  - Transient phacodonesis after circling buckle procedure for rhegmatogenous retinal
      detachment.

PMID- 11450745
TI  - Post-traumatic fungal keratitis caused by Absidia corymbifera, with successful
      medical treatment.

PMID- 11450746
TI  - Stenotrophomonas maltophilia endophthalmitis after penetrating injury by a wooden
      splinter.

PMID- 11450747
TI  - Maxillary antral adenoid cystic carcinoma: an unusual presentation.

PMID- 11450748
TI  - Recurrent sixth nerve palsy following measles mumps rubella vaccination.

PMID- 11450749
TI  - Retinal and orbital arteriovenous malformations.

PMID- 11450750
TI  - Primary acute angle closure glaucoma associated with suprachoroidal fluid in
      three Chinese patients.

PMID- 11450751
TI  - Screening for diabetic retinopathy.

PMID- 11450752
TI  - Late clouding of an acrylic intraocular lens following routine
      phacoemulsification.

PMID- 11450753
TI  - Late clouding on an acrylic intraocular lens following routine
      phacoemulsification.

PMID- 11450754
TI  - In vitro fertilisation and stage 3 retinopathy of prematurity.

PMID- 11450755
TI  - Cataract surgery and the optometrist.

PMID- 11450756
TI  - The role of IgM isotype anticardiolipin antibodies in ocular vaso-occlusive
      disease.

PMID- 11450757
TI  - Driving safety after pupil dilatation.

PMID- 11450758
TI  - Dysversion of lateral eyelashes in children.

PMID- 11450759
TI  - The ageing macula.

PMID- 11450760
TI  - Mechanisms of ageing.
AB  - Recent experimental work from a variety of biological systems, ranging from yeast
      to human beings, lends increasing support to the view that stochastic damage
      inflicted to biological macromolecules is the driving force for the ageing
      process. The damage is derived from small reactive molecules, most prominently
      reactive oxygen intermediates (ROI), that arise during normal cellular metabolism
      and are associated with important if not essential cellular functions. The major
      classes of macromolecules at risk are proteins, lipids and DNA, but damage to DNA
      (both nuclear and mitochondrial) may entail particularly severe consequences.
      Cellular dysfunction resulting from macromolecular damage can be detected as a
      variety of expressions, such as genomic instability, inappropriate cell
      differentiation events or cell death. While for post-mitotic cell types
      replacement of the dead cell by another cell of the same lineage is not possible,
      mitotic cell types may initially replace dead cells via cell proliferation. But
      exhaustion of the self-renewal capacity of the respective lineage, by either
      replication-associated or damage-associated telomere shortening, will ultimately
      also lead to loss of parenchymal cell mass and functional impairment of tissues,
      the latter being a typical feature of ageing of tissues and organs. It has been
      demonstrated in various experimental systems that the rate ageing of can be
      retarded by lowering the production of endogenous ROI or by improving cellular
      anti-oxidative defences. Whether augmentation of cellular DNA repair capacity
      will have the same effect remains to be seen.

PMID- 11450761
TI  - Photoreceptor topography in ageing and age-related maculopathy.
AB  - The relative rate of rod and cone degeneration is a fundamental characteristic of
      any disorder affecting photoreceptors, including ageing and age-related
      maculopathy (ARM). The macula consists of a small cone-dominated fovea surrounded
      by a rod-dominated parafovea. In donor eyes with grossly normal maculas, the
      number of foveal cones is stable and the number of parafoveal rods decreases by
      30% over adulthood. These trends continue in early ARM. In exudative ARM, the
      photoreceptors that survive over disciform scars are largely cones, and rods
      decline precipitously in relation to thick subretinal pigment epithelium
      deposits. The preferential vulnerability of rods over cones has been confirmed by
      recent functional studies showing that the loss of scotopic sensitivity is
      greater than the loss of photopic sensitivity throughout adulthood and in
      patients with early ARM. A hypothesis that these effecfs are due to to retinoid
      deficiency at the level of the photoreceptors is proposed. The topography of rod
      loss in ageing and ARM is consistent with the location of early ARM lesions
      described in population-based studies and is not consistent with the location of
      fundus autofluorescence due to lipofuscin.

PMID- 11450762
TI  - The role of the retinal pigment epithelium: topographical variation and ageing
      changes.
AB  - The retinal pigment epithelium (RPE) is a single layer of post-mitotic cells,
      which functions both as a selective barrier to and a vegetative regulator of the
      overlying photoreceptor layer, thereby playing a key role in its maintenance.
      Through the expression and activity of specific proteins, it regulates the
      transport of nutrients and waste products to and from the retina, it contributes
      to outer segment renewal by ingesting and degrading the spent tips of
      photoreceptor outer segments, it protects the outer retina from excessive high
      energy light and light-generated oxygen reactive species and maintains retinal
      homeostasis through the release of diffusible factors. The ageing characteristics
      of the RPE suggest that in addition to cell loss, pleomorphic changes and loss of
      intact melanin granules, significant metabolic changes occur resulting, at least
      in part, from the intracellular accumulation of lipofuscin. This pigment has been
      shown to be highly phototoxic and has been linked to several oxidative changes,
      some leading to cell death. While the aetiology of age-related macular
      degeneration is complex and is as yet unresolved, it is likely that accelerated
      ageing-like changes in the RPE play a fundamental role in the development of this
      condition.

PMID- 11450763
TI  - Structure and composition of drusen associated with glomerulonephritis:
      implications for the role of complement activation in drusen biogenesis.
AB  - PURPOSE: The ocular fundi of many patients with membranoproliferative
      glomerulonephritis type II (MPGN-II) are characterised by the presence of
      deposits within Bruch's membrane that resemble drusen, hallmark lesions
      associated with age-related macular degeneration (AMD). Glomerulonephritis (GN)
      associated drusen appear at a younger age, however, than do drusen in individuals
      with AMD. In light of recent evidence that immune-mediated events participate in
      drusen biogenesis and AMD, we examined the structure and composition of drusen in
      eyes obtained from human donors with two distinct glomerulopathies, both of which
      involve complement deposition within glomeruli. These features were compared with
      those of drusen from patients with clinically documented AMD. METHODS: Eyes
      obtained from two human human donors diagnosed with membranous and post
      streptococcal GN, respectively, were analysed histochemically,
      immunohistochemically and ultrastructurally. RESULTS: Subretinal pigment
      epithelial (RPE) deposits in both types of GN are numerous and indistinguishable,
      both structurally and compositionally, from drusen in donors with AMD. GN
      associated drusen exhibit sudanophilia, bind filipin, and react with antibodies
      directed against vitronectin, complement C5 and C5b-9 complexes, TIMP-3 and
      amyloid P component. Drusen from the membranous GN donor, but not the post
      streptococcal GN donor, reacted with peanut agglutinin and antibodies directed
      against MHC class II antigens and IgG. The ultrastructural characteristics of
      these deposits were also identical with those of AMD-associated drusen.
      CONCLUSIONS: The composition and structure of ocular drusen associated with
      membranous and post-streptococcal/segmental GN are generally similar to those of
      drusen in individuals with AMD. In view of the recent data supporting the
      involvement of complement activation in drusen biogenesis and the pathobiology of
      AMD, further studies of the biological relationships between AMD and diseases
      associated with complement activation are warranted.

PMID- 11450764
TI  - Age-related maculopathy: its genetic basis.

PMID- 11450765
TI  - Strategies for mapping susceptibility genes in age-related maculopathy.
AB  - The prospects for mapping genes conferring susceptibility to common disorders
      such as age-related maculopathy have increased as a result of advances in high
      throughput genotyping using single nucleotide polymorphisms. This should not
      obscure the magnitude of the task of identifying what are potentially a diverse
      group of genetic variants with small or intermediate effects on disease
      susceptibility. Strategies for increasing the odds of success in such an
      endeavour are discussed.

PMID- 11450766
TI  - Photodynamic therapy in the treatment of subfoveal choroidal neovascularisation.
AB  - Subfoveal choroidal neovascularisation (CNV) is a major cause of visual
      disability, with age-related macular degeneration (AMD) the commonest cause.
      Confluent laser to CNV significantly reduces severe visual loss but the profound
      visual loss after treatment of subfoveal lesions and the high recurrence rate has
      meant its restriction to extrafoveal lesions. Developed initially as a treatment
      for cancers, photodynamic therapy (PDT) has been shown to successfully close CNV
      in the eye. Large international randomised placebo-controlled studies of the
      safety and efficacy of PDT with verteporfin are under way. The Treatment of Age
      related Macular Degeneration with Photodynamic Therapy (TAP) study has
      demonstrated a reduction of visual loss in treated patients with any classic CNV.
      Subgroup analysis showed a greater benefit in predominantly classic lesions (p <
      0.001, NNT: 3.6), increasing further for lesions with no occult component,
      roughly equivalent to pure classic (p < 0.01, NNT: 2.2) A significant benefit at
      12 months has been shown in patients with CNV secondary to myopia in the
      Verteporfin in AMD (VIP) trial, but no benefit in pure occult lesions. Further
      research is required to establish cost-effectiveness and appropriate referral
      patterns in the UK and optimise treatment strategies. Further data are awaited
      from TAP/VIP. At present verteporfin PDT is indicated in eyes with subfoveal
      predominantly classic CNV secondary to AMD with visual acuity of 6/60 or better
      and lesions < 5,400 microm in diameter. Juxtafoveal lesions meeting the above
      criteria and CNV secondary to pathological myopia should also be considered for
      treatment. The efficacy of treatment of larger lesions, juxtapapillary CNV,
      occult/no classic with high-risk characteristics (HRC) and CNV from other causes
      remains unclear. The treatment of minimally classic lesions and those with
      occult/no classic without HRC is not indicated.

PMID- 11450767
TI  - Limited macular translocation.

PMID- 11450768
TI  - Neovascular age-related macular degeneration: present and future treatment
      options.
AB  - PURPOSE: To review treatment strategies in neovascular age-related macular
      degeneration (ARMD). METHODS: Medline and Embase search. RESULTS: Age-related
      macular degeneration (ARMD) is the commonest cause of blindness in the developed
      world in individuals over 50 years of age. ARMD may lead to loss of vision by
      atrophy of the retinal pigment epithelium or by the development of choroidal
      neovascular membranes (CNVM) under the macula, which leak serous fluid and blood
      and ultimately cause a blinding disciform scar. Treatment options currently being
      investigated fall into three main approaches: elimination of the CNVM from the
      subfoveal area (by laser or surgery), modification of the CNVM (by laser,
      radiotherapy or chemotherapeutic agents) or lastly prevention of the formation of
      CNVM (by laser prophylaxis, diet or gene targeting). Whilst almost no therapy
      restores normal visual acuity, any significant visual improvement over the
      natural history may be regarded as beneficial. CONCLUSIONS: Both the current and
      immediate future potential therapies for choroidal neovascularisation in ARMD
      require considerable advances to be made before they will make any impact on
      blindness caused by ARMD. Of the current treatments none are curative and the
      treatment benefits are small. There is an urgent need for new therapies.

PMID- 11450769
TI  - Vision rehabilitation for patients with age-related macular degeneration.

PMID- 11450770
TI  - Trauma attending in the resuscitation room: does it affect outcome?
AB  - Although there are no Class I data supporting the regionalization of trauma care
      the consensus is that trauma centers decrease morbidity and mortality. However,
      the controversy continues over whether trauma surgeons should be in-house or take
      call from home. The current literature does not answer the question because in
      all of the recent studies the attendings who took call from home were in the
      resuscitation room guiding the care. We believe the correct question is: Does the
      presence of the trauma attending in the resuscitation room make a difference? At
      a university-affiliated Level II trauma center data from the trauma registry,
      resuscitation room flowsheet, and dictated admission notes were reviewed on all
      patients over a 6-month period. Data points were: attending present in the
      resuscitation room, standard demographics, resuscitation room time, time to
      operating room (OR), time to CT scan, length of stay, complications, and
      mortality. A total of 943 patients were studied with 216 (23%) having the
      attending present in the resuscitation room and 727 (77%) without the attending
      present. The groups were similar in terms of age, sex, Injury Severity Score,
      percentage Injury Severity Score greater than 15 (16-17.1%), and mechanism of
      injury (24-29% penetrating). Of all the data points studied only time to the OR
      had a statistically significance difference (P < 0.05) with it taking 43.8
      minutes (+/-20.1) when the attending was present and 109.4 minutes (+/-107) when
      the attending was absent. There were also no missed injuries, delays to the OR,
      or inappropriate workups when the attendings were present. Only the time to the
      OR reached statistical significance. The time to the OR is indicative of the
      decision-making process in the resuscitation room, and it is in this area that
      the attendings' presence is the most useful. Also, we believe that it is
      important that there were no missed injuries, delays to the OR, or inappropriate
      workups when the attendings were present in the resuscitation room. This again
      speaks to the decision-making process. We believe that these data support the
      need for the attending to be present in the resuscitation room to facilitate
      accurate and timely decisions regardless of whether they take the call from home
      or in-house.

PMID- 11450771
TI  - Emergency laparotomy in patients on continuous ambulatory peritoneal dialysis.
AB  - Peritonitis is the most common complication of chronic ambulatory peritoneal
      dialysis (CAPD). It is often a diagnostic challenge to differentiate those
      patients with CAPD-associated infections from those who have unrelated
      gastrointestinal pathology as the cause of peritonitis and would benefit from
      surgical exploration. A retrospective chart review was performed on all patients
      at a single institution who were on CAPD between the years 1990 and 1998 and who
      underwent laparotomy for peritonitis. Six patients underwent laparotomy. Four
      were male and two were female; ages ranged from 34 to 80 years. Perforated
      appendicitis was the cause of peritonitis in three patients, perforated
      diverticulitis was present in two, and one was without any suppurative intra
      abdominal process. In each case CT scan of the abdomen was nondiagnostic. There
      was a delay in diagnosis of 10 days (range 3-21 days) and an operative mortality
      of 16 per cent.

PMID- 11450772
TI  - Multiloculated peritoneal inclusion cysts with splenic involvement: a case
      report.
AB  - Multilocular peritoneal inclusion cysts (MPICs) are most commonly found in women
      of reproductive years and involve the abdomen, pelvis, and retroperitoneum. It is
      commonly thought that these cysts are due to an inflammatory reaction. Patients
      usually present with chronic abdominal or pelvic pain and are diagnosed by
      ultrasound or CT scan. Although there are experimental medical treatment options
      surgical excision remains the current recommended primary therapy for symptomatic
      disease. The following case describes a pregnant female with rare MPIC involving
      the spleen and peritoneum. Biological behavior of MPIC and current therapy
      options are also discussed.

PMID- 11450773
TI  - Rectal prolapse: a search for the "best" operation.
AB  - There is a lack of consensus regarding the optimal operative treatment for full
      thickness rectal prolapse. We describe our experience in the management of
      procidentia and evaluate our current practice for improvement of results. The
      medical records of patients undergoing surgery for rectal prolapse between 1989
      to 1999 were retrospectively reviewed. A total of 36 perineal
      proctosigmoidectomies (PPSs) and 29 abdominal procedures [17 anterior resections
      (ARs) and 12 Ripstein procedures (RPs)] were performed during the 10-year period.
      Patients undergoing PPS were significantly older and had more comorbidities. Mean
      operating time and length of hospital stay were shorter for the PPS group. Early
      and late postoperative complication rates were also significantly lower in the
      PPS group. Six patients (16%) in the PPS group developed recurrence at a mean
      follow-up of 50 months. Operation under general anesthesia or removal of a longer
      segment of prolapsed bowel did not reduce recurrence after PPS. No full-thickness
      recurrence was noted after AR or RP. We conclude that abdominal procedures (AR
      and RP) have the lowest recurrence but at a significantly higher cost in terms of
      complications. PPS is a valuable option in selected patients and can be performed
      with minimal morbidity and a relatively low recurrence rate.

PMID- 11450774
TI  - Amyand's hernia: a case report of an incarcerated and perforated appendix within
      an inguinal hernia and review of the literature.
AB  - Appendicitis within an Amyand's hernia is rare; when it occurs it is often
      misdiagnosed as a strangulated inguinal hernia. We present a case report of such
      a case and a review of the literature. It is our recommendation that repair
      should be undertaken without the use of synthetic mesh through a properitoneal
      incision that gives access to the peritoneal cavity and the inguinal regions.

PMID- 11450775
TI  - Modification of a choledochoscope for extraction of difficult biliary stones.
AB  - Cholelithiasis is a common problem in the United States, affecting 10 to 15 per
      cent of the population. Although only one per cent of these patients have
      intrahepatic gallstones their discovery intraoperatively may present a technical
      challenge for the surgeon. This paper describes a simple method for dislodging
      difficult intrahepatic biliary stones: modification of a rigid choledochoscope to
      permit use of a biliary Fogarty catheter and Segura basket under direct
      visualization.

PMID- 11450776
TI  - A rare case of primary group A streptococcal peritonitis.
AB  - Primary Group A streptococcal peritonitis is a rare clinical entity that is
      almost always associated with underlying disease. Group A streptococcus commonly
      causes upper respiratory tract infections and cutaneous infections such as
      impetigo and erysipelas. However, Group A streptococcus has rarely been
      associated with gastrointestinal infections. This is a case report describing a
      previously healthy adult male who developed primary Group A streptococcal
      peritonitis. Diagnostic laparoscopy resulted in identification of peritonitis
      without an identifiable intra-abdominal source. Appropriate antibiotic therapy
      was instituted. Culture of blood, sputum, urine, and urethra were all pathogen
      free. The patient made a complete recovery and was dismissed from the hospital on
      oral clindamycin and cephalexin. To the best of our knowledge this report
      represents the only documented case of primary Group A streptococcal peritonitis
      in a male patient without any significant past medical history.

PMID- 11450777
TI  - Complication of the retroperitoneal approach: intercostal abdominal hernia.
AB  - The left thoracoabdominal incision with retroperitoneal dissection offers
      excellent exposure of the abdominal and thoracic aorta. Disadvantages to this
      approach include inadequate access to the right ileofemoral arterial segments and
      the right renal artery. Additional difficulties with this approach include flank
      bulges, hernias, and neuropathy. We present a case of an incisional hernia at the
      tenth interspace with subsequent herniation of the left colon through this
      defect. CT defined the extent of this defect and ruled out other significant
      pathology. The patient underwent an uneventful herniorrhaphy. Abdominal
      intercostal hernias have not been previously reported in association with the
      retroperitoneal aortic repair.

PMID- 11450778
TI  - Cholecystitis in the octogenarian: is laparoscopic cholecystectomy the best
      approach?
AB  - Management of biliary disease in the octogenarian has evolved over the last
      decade. Laparoscopic cholecystectomy is now more commonly performed in this
      patient population. Octogenarians with biliary pathology frequently present with
      complications of acute disease such as biliary pancreatitis, choledocholithiasis,
      and acute cholecystitis. As a result, laparoscopic management in this patient
      population can frequently be more challenging than in younger patients. We
      retrospectively reviewed 70 patients who were 80 years of age and older who
      underwent cholecystectomy at our institution for biliary tract disease. Seventeen
      patients presented to the Day Surgery unit for elective management of chronic
      biliary disease. Sixteen (94%) of these patients were attempted laparoscopically
      and one (6%) underwent open cholecystectomy. Two patients attempted
      laparoscopically were converted to open surgery (conversion rate 12.5%). Average
      length of hospital stay was 3.7 days for those treated laparoscopically and 11
      days for patients treated with open cholecystectomy. There were three
      complications (19%) in this group and no deaths. The remaining 53 patients
      presented via the emergency room with acute complications of cholelithiasis.
      Laparoscopic cholecystectomy was attempted in 28 (52%) and open cholecystectomy
      was performed in 25 (48%) patients. Ten (37%) of the patients attempted
      laparoscopically were converted to an open procedure. Average length of stay in
      this group was 11.7 days for those treated laparoscopically and 15.7 days for
      patients managed with open technique. There were ten (56%) complications in the
      laparoscopic group and five (14%) complications in the open group. There were
      four deaths (22%) among those treated laparoscopically and three deaths (8.6%) in
      the open cholecystectomy group. Comorbid conditions were common in the patients
      with acute biliary pathology and those presenting for elective cholecystectomy.
      Laparoscopic cholecystectomy is the procedure of choice in the elective
      management of biliary tract disease in the octogenarian. Laparoscopic
      cholecystectomy has no benefit with respect to morbidity and mortality over open
      cholecystectomy in the management of acute biliary tract disease in this elderly
      population. When possible, chronic cholecystitis in the elderly should be managed
      with elective laparoscopic cholecystectomy rather than waiting for complications
      to develop.

PMID- 11450779
TI  - Current assessment of thromboembolic disease and pregnancy.
AB  - This study was undertaken to assess incidence of deep venous thrombosis and
      pulmonary emboli in an inner-city pregnant population. Thromboembolic disease is
      believed to occur in 0.05 to 0.1 per cent of all pregnancies. Historically,
      postpartum thromboembolic disease was more common; decreased hospital stay may
      shift the thromboembolic disease to the antepartum period. A 5-year retrospective
      review of 4910 births assessed for incidence of thromboembolic disease, methods
      of diagnosis and treatment, and risk factors. A total of 4910 deliveries with
      3978 transvaginal resulted in 30 episodes of deep venous thrombosis and five
      pulmonary emboli. All incidences of deep venous thrombosis but one were left
      sided; four of five pulmonary emboli were postpartum. Of the epidsodes of deep
      venous thrombosis 17 per cent were first trimester, 50 per cent second trimester,
      27 per cent third trimester, and 6 per cent postpartum. The diagnosis was
      confirmed by duplex scan in 24 of 30 patients. Heparin was the standard
      treatment. Deep venous thrombosis in pregnancy is most common in the second
      trimester; pulmonary emboli remain most common postpartum.

PMID- 11450780
TI  - HIV/AIDS and the risk of deep vein thrombosis: a study of 45 patients with lower
      extremity involvement.
AB  - Many aspects of acquired immunodeficiency syndrome (AIDS) have been described in
      detail in the literature. However, there have been very few articles on the
      phenomenon of deep vein thrombosis (DVT) in the lower extremities of human
      immunodeficiency virus (HIV)/AIDS patients. The objective of this communication
      is to record the incidence of DVT in HIV/AIDS patients and the risks for
      development of embolic events and to emphasize the need for prevention and for
      the vigorous treatment of this complication. We conducted a retrospective review
      of HIV/AIDS-infected patients with DVT admitted to Mount Sinai School of
      Medicine/Cabrini Hospital in New York during the last 5 years. Analysis includes
      demographic data; risk factors for HIV/AIDS infection; associated medical
      problems; recent surgery; and laboratory findings including CD4 counts, platelet
      counts, prothrombin times, partial thromboplastin times, and plasma albumin
      levels; and image studies. From January 1995 to January 2000 4752 HIV/AIDS
      infected patients were admitted. Of those admitted to the hospital 45 (0.95%)
      were found to have DVT. There were 36 males and nine females (mean age 43 years).
      Of the 45 patients 38 had infectious complications and 13 developed a malignancy.
      The distribution of the thromboses were the femoral vein in 23 patients, the
      popliteal vein in 20 patients, and the iliofemoral system in 2 patients. Twelve
      patients had recurrent DVT and three patients developed a pulmonary embolism.
      HIV/AIDS infection is a considerable risk for development of DVT in the lower
      extremity. Statistically DVT in HIV/AIDS is approximately 10 times greater than
      in the general population. Emphasis upon prevention and vigorous treatment of DVT
      is recommended.

PMID- 11450781
TI  - The demands of screening mammography on surgical inpatient services of breast
      cancer.
AB  - A nationwide mammographic screening of women ages 50 to 59 years commenced in
      Finland in January 1987. We studied the demands of screening on surgical
      inpatient services by comparing the treatment strategy, volume of breast
      biopsies, and hospital stay before and after implementation of mass screening of
      women age 50 to 59. Approximately 20 patients per 100,000 inhabitants were
      referred annually from mass screening for surgical biopsies, in half of which
      cancer was detected. In 1985 through 1986 (before screening) we operated on 134
      patients suspected of having breast cancer. After the first (in 1990) and the
      second (in 1995) round of mammographic screening we operated on 161 patients in 2
      years suspected of having breast cancer. Concurrently 25 of 92 cancers (27%) were
      found only because of the screening. Before the screening period clinical
      symptoms and palpable tumors were cause for referral to surgery in 84 per cent of
      the cases and abnormal mammography in only 16 per cent. During screening these
      ratios were 34 and 61 per cent, respectively. The number of T(is)-1 cancers (<2
      cm) increased from 44 per cent before screening to 70 per cent during screening.
      In contrast the number of T2 cancers (2-4 cm) decreased from 40 to 20 per cent.
      The mammographic screening did not increase the hospital stay of patients. We
      conclude that the mammographic screening program of all women age 50 to 59 years
      increased the number of surgical biopsies in our hospital by only 30 per cent.
      Breast cancer was found at an earlier stage during screening. More than one
      fourth of breast cancers are currently found through the mass screening program
      in Finland.

PMID- 11450782
TI  - Ulcerative colitis and colonic lymphoma: a theoretical link.
AB  - Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum.
      Although colonic adenocarcinoma is a recognized complication of UC there have
      been few reported cases of gastrointestinal lymphoma arising in this setting. We
      describe our experience with such a case and review the literature that attempts
      to explain possible genetic etiologies for the malignant transformation of
      gastrointestinal lymphoid tissue to lymphoma as well as a link between UC and
      lymphoma.

PMID- 11450783
TI  - Ectopic supernumerary kidney, a cause of para-aortic mass: case report and
      review.
AB  - Ectopic supernumerary kidney is a rare congenital urinary tract abnormality.
      Because of the scarcity of published cases and atypical presenting symptomatology
      this entity frequently causes a diagnostic as well as therapeutic dilemma. We
      report a case of an unusually symptomatic supernumerary kidney that presented as
      back pain. Noncontrast CT scan showed a suspicious left-sided para-aortic mass,
      which prompted a percutaneous biopsy. Intravenous contrast CT scan revealed an
      anatomically and functionally free supernumerary kidney. The approach to
      diagnosis as well as management of supernumerary kidneys is discussed herein.

PMID- 11450784
TI  - Efficacy of thoracic computerized tomography in blunt chest trauma.
AB  - Studies suggest that thoracic computed tomography (TCT) is superior to plain
      chest X-ray (CXR) in the detection of blunt chest injury. This study examined
      whether TCT provides additional information to routine CXR findings, whether the
      additional information results in a management change, and whether TCT is more
      useful in patients with particular mechanisms of injury. Level I trauma patients
      were prospectively placed into two groups. Control (CTL) group patients underwent
      TCT as a result of either clinical chest symptoms or abnormal CXR findings. The
      mechanism (MECH) group contained patients who had no thoracic signs and a
      negative CXR but experienced severe mechanisms of injury. TCT identified injuries
      not seen on CXR in 66 per cent of the CTL group and 39 per cent of the MECH
      group. Identification of these injuries resulted in a highly significant (P <
      0.001) change in clinical management in 20 per cent of the CTL group and 5 per
      cent of the MECH group. TCT appears to be most helpful in the acute evaluation of
      trauma patients when roentgenographic evidence of chest injury exists and
      provides additional information impacting on the care of the patient 20 per cent
      of the time. In patients with severe mechanisms of injury and normal CXRs TCT
      expeditiously identifies occult chest injuries that require treatment in 5 per
      cent of this population.

PMID- 11450785
TI  - Trauma-specific intensive care units can be cost effective and contribute to
      reduced hospital length of stay.
AB  - Our hypothesis was that clinical outcomes are improved and cost and hospital
      length of stay (LOS) reduced as a result of the opening of a closed trauma
      intensive care unit (ICU). We conducted a cross-sectional study in a university
      affiliated Level I trauma center. Our study population comprised trauma patients
      admitted to the ICU between June 1, 1996 and July 1, 1998 for at least 24 hours
      and with an Injury Severity Score (ISS) >16 (excluding those with severe brain
      injury). The main outcome measures were changes in LOS and number of ventilator
      days, prevalence of complications, changes in patient charges, and hospital
      costs. Two hundred four patients were included [trauma ICU (TICU) 60, surgical
      ICU 144]. The two groups were not statistically different in age, ISS, mechanism
      of injury, infection rate, and mortality; however, the TICU patients had a lower
      number of ventilator hours (83.1 vs 100.0; P = 0.007), lower ICU LOS (9.4 vs 12.1
      days; P = 0.06), and lower total hospital LOS (15.6 vs 22.3 days; P = 0.01).
      Although this was not of statistical significance TICU patients had lower
      hospital charges ($125,383 vs $152,994; P = 0.06) and lower cost per case
      ($42,306 vs $47,548; P = 0.35) for a net savings of $314,520 during the first 6
      months of operation of the TICU. This study suggests that improved clinical
      outcomes and decreases in cost and LOS are directly related to the opening of a
      closed trauma ICU.

PMID- 11450786
TI  - Pure squamous cell carcinoma of the breast in a patient with previous
      adenocarcinoma of the breast: a case report and review of the literature.
AB  - We report a case of squamous cell carcinoma of the breast in a patient with
      previous adenocarcinoma in the unilateral breast. Squamous cell carcinoma is
      often cystic in nature with a variable presentation on mammogram. Its diagnosis
      necessitates the preclusion of a primary site of squamous carcinoma elsewhere in
      the body. The treatment of this cancer is similar to other types of breast
      carcinoma. Its prognosis remains unclear.

PMID- 11450787
TI  - Routine perioperative pulmonary artery catheterization has no effect on rate of
      complications in vascular surgery: a meta-analysis.
AB  - Despite widespread use pulmonary artery catheterization has not been proven to
      reduce complications or mortality. One study supported the use of routine
      preoperative pulmonary artery catheterization in moderate-risk vascular surgery
      patients; several other studies have reported that pulmonary artery
      catheterization is not efficacious. Our goal was to scrutinize the data using
      meta-analysis. This is a systematic review of the literature. MEDLINE was
      searched for all articles on pulmonary artery catheterization, optimization,
      oxygen delivery, and preoperative preparation of vascular surgery patients. Data
      from papers judged appropriate for inclusion were analyzed using a computer
      program, Easy MA. Complications were defined as only those that could have
      reasonably have been prevented by or resulted from pulmonary artery
      catheterization. Of hundreds of possible papers only four were found to be
      adequate randomized prospective studies with similar exclusions, therapeutic
      endpoints, and interpretable complication and mortality rates. Controls included
      174 patients versus 211 in the protocol group. Power analysis showed that the
      combined sample sizes were adequate. The meta-analysis demonstrates that the
      studies are homogeneous. The use of a pulmonary artery catheter does not prevent
      morbidity or mortality. Of the studies providing data on the amount of
      intravenous fluid administered three reported that statistically significantly
      more fluid was given to patients who underwent pulmonary artery catheterization.
      Meta-analysis indicates that in moderate-risk vascular surgery patients routine
      preoperative pulmonary artery catheterization is not associated with improved
      outcomes.

PMID- 11450788
TI  - Antiretroviral-induced hepatic steatosis and lactic acidosis: case report and
      review of the literature.
AB  - As the prevalence of human immunodeficiency virus (HIV) infection continues to
      rise the clinician is encountered with a diagnostic challenge. Nonsurgical
      diseases such as acute colitis or enteritis can appear similar to such true
      surgical emergencies as abscess, perforation, or mesenteric ischemia. We report a
      case of fulminant hepatic failure associated with didanosine and masquerading as
      a surgical abdomen and compare the clinical, biologic, histologic, and
      ultrastructural findings with reports described previously. This entity should be
      kept in mind when evaluating the acute abdomen in the HIV-positive patient.

PMID- 11450789
TI  - Cyanide toxicity in the surgical intensive care unit: a case report.
AB  - Hypertension is a widespread entity in the surgical intensive care unit. Not only
      is the clinical spectrum varied, but the armamentarium available to the clinician
      is also wide-ranging. Sodium nitroprusside, a potent vasodilator with a short
      half-life, is often used for hypertensive crisis and to deliberately maintain a
      low blood in certain clinical conditions. Cyanide toxicity is a known
      complication of sodium nitroprusside use. Herein is reported a case of probable
      cyanide toxicity in an elderly trauma patient. The pharmacology of sodium
      nitroprusside and the pitfalls of making the diagnosis of cyanide toxicity are
      discussed.

PMID- 11450790
TI  - Magnification views of mammography decrease biopsy rates.
AB  - Mammography is a valuable tool for screening and has increased early detection of
      breast cancer. Magnification views are commonly used to further elucidate
      suspicious changes seen on routine mammograms. The effect of magnification views
      and their utility have not been studied regarding the influence on treatment
      strategies. All patients who had magnification views performed along with their
      mammogram at Tulane University Medical Center over a one-year period were
      included. Patient charts were reviewed for mammogram readings, recommendations,
      and any biopsy results. The original mammograms without the magnification views
      were given to a physician who was blinded to the final results of the
      magnification views for a recommendation of whether or not to biopsy the lesion.
      These recommendations were compared with the results with actual recommendations.
      Magnification views were performed on 127 patients. After the additional
      magnification views were taken 27 per cent (34 of 127) of patients had biopsies
      performed. Biopsy results revealed benign findings in 71 per cent and nonbenign
      findings (lobular carcinoma in situ, ductal carcinoma in situ, or carcinoma) in
      29 per cent. On the basis of the recommendations without magnification views 64
      per cent of patients would have had biopsies performed. Magnification views
      decreased the biopsy rates by 58 per cent (P < 0.001; chi2 tests). Magnification
      views can help decrease the number of biopsies performed for suspicious small
      areas on mammograms. Their judicious use can help decrease unnecessary
      procedures, patient anxiety, and cost. Magnification views are useful to help
      surgeons and radiologists best screen for breast cancer.

PMID- 11450791
TI  - Mechanical tracheal obstruction due to an intramural esophageal hematoma
      following endoscopic variceal sclerotherapy.
AB  - Endoscopic injection sclerotherapy is widely used as treatment for bleeding
      esophageal varices. Esophageal intramural hematoma is a rare complication
      following endoscopic injection sclerotherapy. Patients present with pain and
      dysphagia due to esophageal obstruction. We present the first reported case of
      respiratory failure resulting from an intramural hematoma causing posterior
      tracheobronchial compression. Although patients with alcoholic cirrhosis and
      bleeding varices requiring respiratory support generally have a poor prognosis
      this may be an occasion when ventilatory support may be expected to be easily
      withdrawn after hematoma resolution.

PMID- 11450792
TI  - The impact of pre-existing end-stage renal disease on survival in acutely injured
      trauma patients.
AB  - End-stage renal disease and associated dialysis procedures alter homeostatic
      mechanisms and adversely affect the respiratory, cardiac, and central nervous
      systems. Currently outcomes research in acutely injured trauma patients utilizes
      Trauma and Injury Severity Score methodology with the Injury Severity Score and
      Revised Trauma Score, which do not account for comorbidities. Literature has yet
      to emerge that analyzes the effects of end-stage renal disease on acutely injured
      trauma patients. A retrospective review at an urban Level I trauma center was
      performed of all end-stage renal disease patients' medical records who were
      admitted for acute traumatic injury from 1994 through 1997. The charts were
      abstracted for age, sex, race, method of dialysis, specific injury, need for
      operation, etiology of trauma, length of stay, disposition from hospital,
      morbidity, and mortality. The Injury Severity Score; probability of survival; and
      W, M, and Z statistics were then calculated. The data collected were then
      compared with the overall data for the trauma center including patients with and
      those without end-stage renal disease during this time period. Mortality for
      patients with end-stage renal disease after suffering an acute traumatic injury
      is 2.45 that of the general population. Increased mortality was most prevalent in
      operative patients and those with Injury Severity Score >15. The average length
      of stay in the hospital was 55.3 per cent longer for patients with end-stage
      renal disease. Pre-existing end-stage renal disease negatively impacts survival
      after traumatic injury. A prospective multicentered study comparing renal
      patients with nonrenal patients is warranted. This would confirm the need for
      databases to account for the increased morbidity and mortality associated with
      end-stage renal disease when calculating probability of survival values for
      acutely injured trauma patients. Similarly future studies analyzing the affects
      of other comorbidities such as diabetes, chronic obstructive pulmonary disease,
      and hypertension on acutely injured trauma patients would help develop a more
      accurate method of predicting outcomes.

PMID- 11450793
TI  - Proximal compared with distal gastric cancer: multivariate analysis of prognostic
      factors.
AB  - The major determinants of the poor prognosis of the patients with proximal-third
      gastric cancer (proximal gastric cancer or PGC) when compared with that of
      patients with more distally located gastric tumors (distal gastric cancer or DGC)
      rely both on the more advanced age and tumor stage at the moment of clinical
      presentation and on the higher postoperative mortality for PGC patients. We
      reviewed hospital records of 707 patients with gastric cancer (187 with PGC and
      520 with DGC) observed during the period 1981 through 1996 at the same surgical
      unit. Demographic and pathological data, type of treatment, and hospital
      morbidity and mortality rates were recorded. Univariate and multivariate survival
      analysis was used to calculate the 5-year survival probabilities with respect to
      the following clinical and pathological variables: age, sex, gross appearance
      according to Borrmann classification, histological type according to Lauren,
      stage of the disease, tumor location, and type of treatment. PGC was associated
      with more advanced tumor stage (P < 0.0001), older age (P = 0.039), and higher
      necessity of extended surgery (P < 0.0001) when compared with DGC. Hospital
      mortality was 9.6 and 5 per cent in PGC and DGC patients respectively (P =
      0.033). Overall 5-year survival was 17.7 and 36.4 per cent in PGC and DGC
      patients (P < 0.0001): 35.9 versus 57.6% (P = 0.0001) and 3.7 versus 7.6 per cent
      (P = 0.03) after radical and palliative surgery respectively. At multivariate
      survival analysis proximal location was found to be independently associated (P =
      0.0007) with poor survival. The multivariate model shows the proximal location as
      an independent predictor of lesser favorable outcome in gastric cancer. The major
      determinants of the poor prognosis of PGC with respect to DGC rely both on the
      more advanced age and tumor stage at the moment of clinical presentation and on
      the higher postoperative morbidity for PGC patients.

PMID- 11450794
TI  - Thermal injury in the elderly: when is comfort care the right choice?
AB  - The factors contributing to a higher mortality rate in elderly thermal injury
      victims are not well delineated. The purpose of this study is to determine the
      impact of the initial injury, medical comorbidities, and burn size on patient
      outcome and to determine a level of injury in this population when comfort care
      is an appropriate first choice. Individual medical records of patients over 65
      years of age admitted to our burn center over a 10-year interval were reviewed
      for patient demographics, mechanism of injury, total body surface area (TBSA)
      burned, medical comorbidities, use of Swan-Ganz catheters, evidence of inhalation
      injury, level of support, and patient outcome. The mechanisms of thermal injury
      were flame (68%), scald (21%) and electrical or chemical contact (11%). Twenty
      six preventable bathing, cooking, and smoking-related injuries were seen (33%).
      The average TBSA was 25 per cent. Average length of stay varied depending on
      outcome. The overall mortality rate for this group was 45 per cent. Patients
      older than 80 years with 40 per cent or greater TBSA burned had a 100 per cent
      mortality rate despite aggressive treatment. Burn wound size correlated better
      with probability of poor outcome than age. Thermal injuries in the elderly are
      becoming more important with the aging of our population. Underlying medical
      problems--specifically chronic obstructive pulmonary disease--do play a role in
      increased patient morbidity and mortality. This study shows that age greater than
      80 years in combination with burns greater than 40 per cent TBSA are uniformly
      fatal despite aggressive therapy. We believe that delaying the start of comfort
      only measures in this situation only prolongs the pain and suffering for the
      patient, the family, and the physician.

PMID- 11450795
TI  - Nitric oxide synthase as a marker in colorectal carcinoma.
AB  - Elevated inducible nitric oxide synthase (iNOS) activity has been found in 60 per
      cent of colon adenomas and 20 to 50 per cent of adenocarcinomas. We postulated
      that high levels of iNOS may increase the invasive and metastatic potential of
      colon carcinoma and could be indicative of survival potential. Data were reviewed
      for 52 patients with colorectal carcinoma diagnosed in 1991 and 1992. Specimens
      were stained for iNOS and catalogued as low-activity staining (LAS) or high
      activity staining (HAS) on the basis of visual evaluation by three pathologists.
      Thirty patients were LAS and 22 HAS. Age, sex, preoperative carcinoembryonic
      antigen, tumor and nodal status, and American Joint Committee on Cancer staging
      were not different between groups. Forty-six per cent of the HAS group remained
      alive after 5 years versus 71 per cent in the LAS group. Survival was
      significantly lower and metastatic status significantly higher in the HAS group.
      Results indicated that iNOS activity may be a prognostic indicator of long-term
      survival potential after treatment for colon cancer. In addition results
      suggested that metastasis was greater in colon carcinoma specimens that maintain
      an activated iNOS and that these cells clinically react more aggressively.
      Conclusions are tempered by the fact that results were based on a limited sample
      size.

PMID- 11450796
TI  - Malignant fibrous histiocytoma of the gallbladder: case report and review of the
      literature.
AB  - Malignant fibrous histiocytoma is a soft tissue sarcoma of mesenchymal origin. It
      can rarely present as a primary gallbladder tumor with only five cases having
      been reported to date in the English literature. Here we report the sixth
      documented case of malignant fibrous histiocytoma of the gallbladder, and we
      review all other cases reported. The outcome of the visceral sarcomas is poor
      when compared with tumors arising from the soft tissues. The treatment of primary
      malignant fibrous histiocytomas of the gallbladder is surgery. However, tumor
      recurrence is the norm even if wide clean margins are obtained. In contrast to
      tumors arising from the extremities the role of adjuvant radiotherapy and
      chemotherapy is less clear in the case of retroperitoneal and visceral sarcomas.
      Our patient is still alive and free of disease 46 weeks after surgery. The fact
      that this is the longest survival reported to date underscores the dismal
      prognosis of this disease.

PMID- 11450797
TI  - The Nobel Prize and why there is a prize in physiology or medicine.

PMID- 11450798
TI  - Imagery-induced interference on a visual detection task.
AB  - The literature on the interaction between visual imagery and visual perception
      provides conflicting outcomes. Some studies show imagery interferes with
      perception whereas others show facilitation on perceptual tasks. The effects of
      visual imagery on a detection task were examined in six experiments. When either
      a bar image (Experiment 1) or an image of the letter 'l' (Experiment 3)
      overlapped with the targets, interference was discovered; however, images not
      overlapping the target did not effect detection (Experiments 2 and 4). Increasing
      the number of target locations caused the interfering effects of the image to
      disappear; however, there was no evidence of facilitation (Experiment 5).
      Physical stimuli interfered with detection whether there was overlap or not
      (Experiment 6). The results indicate that imagery induced interference may be
      lessened with more complex visual displays.

PMID- 11450799
TI  - Reference frame for rapid visual processing of line orientation.
AB  - Detection of a uniquely oriented line element in a background field of uniformly
      oriented line elements depends on the orientation of the background field. Is the
      orientational reference frame for this anisotropy entirely dependent on the
      orientations of structures outside the line-element display, the spatial
      regularity of the stimulus elements, and the direction of gravity? The effects of
      these potential cues were investigated in target-detection experiments with brief
      displays. The anisotropy was found whether or not gravitational or visual cues
      defined an orientational reference frame. Stimulus orientation may be coded with
      respect to the retina or body axis in rapid visual processing.

PMID- 11450800
TI  - Collinear effects on 3-Gabor alignment as a function of spacing, orientation and
      detectability.
AB  - Our ability to align three Gabor patches depends upon their internal carrier
      orientation; we are better at aligning vertical or horizontal patches than
      oblique patches (Keeble and Hess, 1998). However, the tuning of alignment to
      patch orientation has not studied in detail. We measured the alignment of a
      vertical target with reference patches varying in orientation and found it tuned
      to vertical (collinear) patches at centre-to-centre separation of three carrier
      periods, with a steep increase for oblique references and slight downturn for
      horizontal (orthogonal) references. Next, we increased separation between the
      patches, testing collinear, side-by-side, orthogonal and oblique configurations.
      Surprisingly, we found that the tuning for collinear patches was preserved. All
      ten observers tested had lower alignment thresholds for collinear patches. This
      effect extended to an inter-patch separation of 10 carrier periods (20 envelope
      standard deviations). Additionally, we measured contrast detection thresholds for
      the reference patches using the same stimuli. The collinear facilitation of
      alignment was even greater than the collinear facilitation of detection.

PMID- 11450801
TI  - Visual search in peripheral vision: learning effects and set-size dependence.
AB  - Feature search for a light bar with one orientation (or color) embedded in an
      array of bars with a very different orientation (or color) is quick, easy and
      independent of the number of array elements. In contrast, search for a
      conjunction target has a linear response time dependence on the number of
      distractors. Training can improve performance of both these tasks. We report that
      these properties may not be valid for eccentric stimulus presentation. In
      general, the two hemifields are not equally suited to search, and training is
      most effective in the weaker hemifield. In addition, the feature-search
      independence of set-size may not always be valid for stimulus arrays that are
      presented peripherally. Subjects were tested on orientation and color feature
      tasks, and on orientation-color conjunction search with 3 array sizes presented
      at fixation or eccentrically in the right or left hemifield. During a second
      testing session, improvement was so much greater for the non-preferred hemifield
      that sometimes the preference was switched. Surprisingly, preferred hemifield
      performance actually declined for some subjects. Thus, the hemifield preference
      effect seems related to competition, and perhaps an automatic attention-directing
      mechanism. We confirmed the central presentation set-size independence for
      feature search but found a great difference between large and small arrays when
      presentation was lateral. There are two sources of this array size effect: 1.
      Target eccentricity, demonstrated by comparing performance for different target
      locations with the same array size. 2. Target location uncertainty, seen by
      comparing performance for different size arrays when the target elements appeared
      at the same locations. Training also affected the array-size dependence, changing
      search performance from set-size dependent to independent or vice versa at the
      point of greatest training effect.

PMID- 11450802
TI  - Location constancy and its effect on visual selection.
AB  - The present study investigated how location constancy influences selective
      attention to a cued location. The relative effectiveness of target/distractor
      distance and target/distractor compatibility were studied under covert and overt
      attention conditions. Experiment 1 measured reaction time and error rates to a
      scaled target letter that appeared at varied locations from 0.62 to 20 deg.
      Experiments 2 and 3 looked at covert/overt attention when the target location was
      fixed rather than varied within a block of trials. To provide a comprehensive
      assessment of the two primary variables across location constancy conditions,
      effect sizes for these results as well as for related past research (Goolkasian,
      1999; Goolkasian and Tarantino, 1999) are presented. The findings suggest that
      the location of the target (foveal vs peripheral) does not influence attentional
      patterns as much as the consistency of its location. When a target appears at
      varied locations from trial to trial, distractor compatibility effects are in
      general stronger than the effect of target/distractor distance. However, the
      relative importance of these two variables reverses when the presentation
      location of the target is fixed at a constant location.

PMID- 11450803
TI  - Luminance artifacts of cathode-ray tube displays for vision research.
AB  - Phosphor persistence, video bandwidth, DC restoration and high-voltage regulation
      affect the appearance of images presented on cathode-ray tubes (CRTs),
      potentially resulting in differences between nominal and actual stimuli. We
      illustrate these effects by measuring physical parameters of horizontal and
      vertical static and counter-phase flickering gratings, and we illustrate problems
      for vision research by measuring contrast sensitivity to these gratings. We also
      measured the extent to which calibration protocols actually result in the monitor
      being calibrated over its entire area regardless of image size. The results of
      our physical measurements indicate substantial differences between gratings that
      nominally differ only as to orientation. Consistent with these differences, our
      psychophysical measurements indicate different sensitivities when the bars of the
      gratings are parallel or orthogonal to raster lines, regardless of the retinal
      orientation of the gratings. The results of our calibration check show that only
      a small region around the target area of calibration can be regarded as
      effectively linearized, and only if the size of the test image used during the
      check is similar to the size of the calibration patch. Overall, our results
      indicate potentially severe problems with the use of CRTs in vision research, and
      we discuss some published results that are likely to have been affected by these
      problems.

PMID- 11450804
TI  - Symmetry detection across the visual field.
AB  - Humans are extremely sensitive to symmetry when it is foveated but sensitivity
      drops as a symmetrical region of a fixed size is moved into the periphery. A
      psychophysical study was undertaken to determine if eccentricity dependent
      sensitivity loss could be overcome by magnifying stimuli at each eccentricity (E)
      by a factor F = 1 + E/E2, where E2 indicates the eccentricity at which the size
      of a stimulus must be doubled, relative to a foveal standard, to achieve
      equivalent performance. The psychophysical task required subjects to decide on
      each trial in which of two intervals a symmetrical stimulus had been presented.
      Stimuli were presented at a range of sizes and eccentricities (0 to 8 degrees)
      and the probability of a correct discrimination was computed for each condition.
      In Experiment 1, thresholds were measured with stimuli set to maximum available
      contrast and, in Experiment 2, stimuli were presented at a constant multiple of
      contrast detection threshold. In both experiments, a single scaling function
      removed most of the eccentricity dependent variation from the data. However, the
      E2 value recovered for one subject tested in both experiments was larger by about
      65% when stimuli were not equated for visibility. We conclude that symmetry
      detection can be equated across a range of eccentricities by scaling stimuli with
      an E2 in the range of 0.88 to 1.38 degrees. Failure to equate for visibility
      across all viewing conditions may result in an inflated estimate of E2.

PMID- 11450805
TI  - A fast method to estimate kinetic constants for enzyme inhibitors.
AB  - We present a method to determine the reaction type and kinetic constants for
      enzyme inhibitors that decreases the number of experimental assays by at least a
      factor of five. It is based on a new theoretical formalism in terms of
      concentrations that dismisses the requirement of estimating initial velocities.
      Expressions for the time evolution of the concentrations of all the reactants are
      also given.

PMID- 11450806
TI  - About the ranking of isolated habitats with different shapes: an interior-to-edge
      ratio study.
AB  - Isolated habitats can be compared and ranked by comparing their interior-to-edge
      ratio (I/E). We would like to show here that results based on ranking by I/E
      ratio sometimes contradict Diamond's rule, which ranks the most rounded habitat
      (i.e. most compact) as the best one. The reason for this contradiction is the
      frequently overlooked size dependence of the I/E. Being the interior-to-edge
      ratio size dependent, from a given set of habitats of different sizes, compact
      shaped (rounded) habitats might have worse I/E ratios than elongated or irregular
      ones.

PMID- 11450807
TI  - Size dependence of interior-to-edge ratios: size predominates shape.

PMID- 11450808
TI  - Drugs versus diets: disillusions with Dutch health care.
AB  - Biology incorporated into other disciplines is often distorted, alarmingly so in
      some areas of medicine. Together with other forms of bias, this may have
      detrimental effects for patients depending on medical research for their health.
      A case study concerning omeprazole (Losec), one of the acid-suppressive drugs
      against gastric ulcers, and NSAIDs, non-steroid anti-inflammatory drugs, confirms
      that distorted biology together with biased health care policies foster disasters
      in current biomedicine and medical practice. In our country, The Netherlands,
      omeprazole is presumably the most commonly used medication. NSAIDs are also used
      in large quantities, increasingly since they have become available as analgesic
      over-the-counter drugs. Unofficial and official sources tend to inform the
      general public that the drugs promote human health. We argue that their being
      used on a massive scale is actually a medical disaster. The health of many
      patients would be served better if the drugs they take were replaced by proper
      forms of diet, but the pharmaceutical industry, the most potent force affecting
      medication policies, appears to prevent a shift in the balance from over
      medicalization towards healthy life styles. The shift should come from government
      agencies responsible for regulation in the medication market. Policies of these
      agencies are now a dismal failure.

PMID- 11450809
TI  - Butterfly eyespot patterns: evidence for specification by a morphogen diffusion
      gradient.
AB  - In this paper we describe a test for Nijhout's (1978, 1980a) hypothesis that the
      eyespot patterns on butterfly wings are the result of a threshold reaction of the
      epidermal cells to a concentration gradient of a diffusing degradable morphogen
      produced by focal cells at the centre of the future eyespot. The wings of the
      nymphalid butterfly, Bicyclus anynana, have a series of eyespots. each composed
      of a white pupil, a black disc and a gold outer ring. In earlier extirpation and
      transplantation experiments (Nijhout 1980a; French and Brakefield, 1995) it has
      been established that these eyespots are indeed organised around groups of
      signalling cells active during the first hours of pupal development. If these
      cells were to supply the positional information for eyespot formation in
      accordance with Nijhout's diffusion-degradation gradient model, then, when two
      foci are close together. the signals should sum, and this effect should be
      apparent in the detailed shape of the resulting pigment pattern. We give an
      equation for the form of the contours that would be obtained in this manner. We
      use this to test the morphogen gradient hypothesis on measurements of the
      outlines of fused eyespots obtained either by grafting focal cells close
      together, or by using a mutation (Spotty) that produces adjacent fused eyespots.
      The contours of the fused patterns were found to satisfy our equation, thus
      corroborating Nijhout's hypothesis to the extent possible with this particular
      type of experiment.

PMID- 11450810
TI  - Cancer development and progression: a non-adaptive process driven by genetic
      drift.
AB  - The current mainstream in cancer research favours the idea that malignant tumour
      initiation is the result of a genetic mutation. Tumour development and
      progression is then explained as a sort of micro-evolutionary process, whereby an
      initial genetic alteration leads to abnormal proliferation of a single cell that
      leads to a population of clonally derived cells. It is widely claimed that tumour
      progression is driven by natural selection, based on the assumption that the
      initial tumour cells acquire some properties that endow such cells with a
      selective advantage over the normal cells from which the tumour cells are
      derived. The standard view assumes that the transformed bodily cell somehow
      acquires "responsiveness" to natural selection independently of the whole
      organism to which the cell belongs. Yet, it is never explained where such an
      acquired capacity to respond to natural selection by the individual bodily cell
      comes from. This situation poses many difficult questions that so far have been
      left unanswered. For example, there is no explanation why some cells belonging to
      an organised whole and as such having no independent capacity for survival,
      apparently become 'independent' entities, able to respond to selective pressures
      in an autonomous fashion and then to be evaluated by natural selection. Hereunder
      it is argued that such a qualitative change cannot be the consequence of specific
      genetic mutations. Moreover, it is shown that natural selection is unlikely to be
      acting within the organism during tumour development and progression and that
      tumour evolution is a random, non-adaptive process, driven by no fundamental
      biological principle. Thus, mutations in the so-called oncogenes and tumour
      suppressor genes observed in epithelial cancers (that constitute more than 90% of
      all cancers) are not the result of selection for better cellular growth or
      survival under restrictive conditions. Instead, here it is suggested that they
      are the consequence of genetic drift acting upon gene functions that become non
      relevant, either for the individual or the species fitness, once the organism is
      past its reproductive prime and as such, they also become superfluous for cell
      survival in the short term. It is proposed that the origin of cancer is
      epigenetic and it is a consequence of the need for a continued turnover of the
      individuals that constitute a species.

PMID- 11450811
TI  - Links between social understanding and social behavior in verbally able children
      with autism.
AB  - This study investigated the relations between various measures of social
      understanding and social interaction competence in verbally able children with
      autism. Measures of social understanding included measures of verbalizable
      knowledge (false belief understanding, affective perspective taking), as well as
      measures of more intuitive forms of social responsiveness (empathy, concern to
      distress, and initiating joint attention). Two measures of social interaction
      competence were employed: level of engagement with peers on the playground, and
      prosocial behavior in a structured laboratory task. For children with autism,
      initiating joint attention and empathy were strongly related to both measures of
      social interaction competence. No understanding-behavior links were identified
      for a language-age matched comparison sample of developmentally delayed children.
      Several accounts of these understanding-behavior links are considered, including
      the possibility that for children with autism, more impaired forms of
      understanding are more closely linked to behavior because they serve as limits on
      competence.

PMID- 11450812
TI  - The Modified Checklist for Autism in Toddlers: an initial study investigating the
      early detection of autism and pervasive developmental disorders.
AB  - Autism, a severe disorder of development, is difficult to detect in very young
      children. However, children who receive early intervention have improved long
      term prognoses. The Modified Checklist for Autism in Toddlers (M-CHAT),
      consisting of 23 yes/no items, was used to screen 1,293 children. Of the 58
      children given a diagnostic/developmental evaluation, 39 were diagnosed with a
      disorder on the autism spectrum. Six items pertaining to social relatedness and
      communication were found to have the best discriminability between children
      diagnosed with and without autism/PDD. Cutoff scores were created for the best
      items and the total checklist. Results indicate that the M-CHAT is a promising
      instrument for the early detection of autism.

PMID- 11450813
TI  - Commentary: The Modified Checklist for Autism in Toddlers.
AB  - The question of when it is best to screen for autism may only be answered by a
      series of empirical studies. These will be difficult to plan, fund, and conduct,
      and will by necessity take many years because of the need to systematically
      follow up the whole cohort screened. In our study, we identified 19 of the 50
      children with autism by their profile at the 18-month screen (though note that
      some fell out of risk status at the repeat screen 1 month later--thus sacrificing
      sensitivity for improved positive predictive power). Through the subsequent
      surveillance methods we employed, we identified the remaining cases as follows: 5
      at 42 months, 4 between 42 months and 7 years, and 25 at 7 years. We do not mean
      to end on a pessimistic note. Our experiences have been positive both in regard
      to the instrument we developed and the effects that using it have had on the
      health practitioners involved in the research study. In discussion, practitioners
      have commented on the usefulness of knowing what prelanguage and prosocial skills
      can reliably be looked at during the 18-month check. Training using the CHAT and
      eliciting its behaviors improved the skills and confidence of primary health
      practitioners. It is our view that this has had the effect of reducing the age at
      which autism is recognized and cases are referred on for a developmental
      assessment. The work reported by Robins er al. makes an important contribution to
      this ongoing research and clinical process as we attempt to accurately identify
      children with autism at a young age.

PMID- 11450814
TI  - Prevalence of autism in Iceland.
AB  - This clinic-based study estimated the prevalence of autism in Iceland in two
      consecutive birth cohorts, subjects born in 1974-1983 and in 1984-1993. In the
      older cohort classification was based on the ICD-9 in 72% of cases while in the
      younger cohort 89% of cases were classified according to the ICD-10. Estimated
      prevalence rates for Infantile autism/Childhood autism were 3.8 per 10,000 in the
      older cohort and 8.6 per 10,000 in the younger cohort. The characteristics of the
      autistic groups are presented in terms of level of intelligence, male:female
      ratio, and age at diagnosis. For the younger cohort scores on the Autism
      Diagnostic Interview-Revised and the Childhood Autism Rating Scale are reported
      as well. Results are compared with a previous Icelandic study and recent
      population-based studies in other countries based on the ICD-10 classification
      system. Methodological issues are discussed as well as implications for future
      research and service delivery.

PMID- 11450815
TI  - Autistic behavior, FMR1 protein, and developmental trajectories in young males
      with fragile X syndrome.
AB  - In the context of a longitudinal study, we assessed the relationship between
      ratings of autistic behavior, FMR1 protein expression (FMRP), and the
      developmental trajectories of 55 young males with fragile X syndrome. Autistic
      behavior, as measured by the Childhood Autism Rating Scale, was not related to
      FMRP expression. However, autistic behavior was a significant predictor of both
      developmental status and developmental change. Boys with both autistic behavior
      and fragile X syndrome functioned at significantly lower levels of development
      and grew at significantly slower rates than those without autistic behavior. FMRP
      expression accounted for less variance in developmental level than did autistic
      behavior, and was not significantly related to slope (developmental change over
      time). No autistic behavior x FMRP interaction was found.

PMID- 11450816
TI  - Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo
      controlled trial.
AB  - In autism, glutamate may be increased or its receptors up-regulated as part of an
      excitotoxic process that damages neural networks and subsequently contributes to
      behavioral and cognitive deficits seen in the disorder. This was a double-blind,
      placebo-controlled, parallel group study of lamotrigine, an agent that modulates
      glutamate release. Twenty-eight children (27 boys) ages 3 to 11 years (M = 5.8)
      with a primary diagnosis of autistic disorder received either placebo or
      lamotrigine twice daily. In children on lamotrigine, the drug was titrated upward
      over 8 weeks to reach a mean maintenance dose of 5.0 mg/kg per day. This dose was
      then maintained for 4 weeks. Following maintenance evaluations, the drug was
      tapered down over 2 weeks. The trial ended with a 4-week drug-free period.
      Outcome measures included improvements in severity and behavioral features of
      autistic disorder (stereotypies, lethargy, irritability, hyperactivity, emotional
      reciprocity, sharing pleasures) and improvements in language and communication,
      socialization, and daily living skills noted after 12 weeks (the end of a 4-week
      maintenance phase). We did not find any significant differences in improvements
      between lamotrigine or placebo groups on the Autism Behavior Checklist, the
      Aberrant Behavior Checklist, the Vineland Adaptive Behavior scales, the PL-ADOS,
      or the CARS. Parent rating scales showed marked improvements, presumably due to
      expectations of benefits.

PMID- 11450817
TI  - Assessment of neural cell adhesion molecule (NCAM) in autistic serum and
      postmortem brain.
AB  - Studies have identified structural abnormalities in areas of the autistic brain,
      with a pattern suggesting that a neurodevelopmental anomaly took place. Neural
      cell adhesion molecule (NCAM), which is involved in development of the central
      nervous system, was previously shown to be decreased in the serum of autistic
      individuals. In the present study, we measured NCAM protein in the sera from
      controls, patients with autism, siblings of autistic patients, and individuals
      with other neurologic disorders, but found no significant differences. We also
      measured NCAM protein in autistic postmortem brain samples and found the longest
      isoform, NCAM-180, to be significantly decreased. In addition, we investigated
      the mRNA expression of NCAM in these brain samples using cDNA microarrays and RT
      PCR. Results show that NCAM mRNA levels are not altered in autism.

PMID- 11450818
TI  - Children's attitudes and behavioral intentions toward a peer with autistic
      behaviors: does a brief educational intervention have an effect?
AB  - This study examined children's ratings of attitudes and behavioral intentions
      toward a peer presented with or without autistic behaviors. The impact of
      information about autism on these ratings was investigated as well as age and
      gender effects. Third- and sixth-grade children (N = 233) were randomly assigned
      to view a video of the same boy in one of three conditions: No Autism, Autism, or
      Autism/Information. Children at both grade levels showed less positive attitudes
      toward the child in the two autism conditions. In rating their own behavioral
      intentions, children showed no differences between conditions. However, in
      attributing intentions to their classmates, older children and girls gave lower
      ratings to the child in the autism conditions. Information about autism did not
      affect ratings of either attitudes or behavioral intentions as ascribed to self
      or others.

PMID- 11450819
TI  - The development of a stress survey schedule for persons with autism and other
      developmental disabilities.
AB  - The Stress Survey Schedule is an instrument for measuring stress in the lives of
      persons with autism and other developmental disabilities. Development of the
      survey and analysis of the underlying measurement structure of the instrument is
      reported in three studies. Through the use of exploratory and confirmatory
      analysis procedures, eight dimensions of stress were identified:
      Anticipation/Uncertainty, Changes and Threats, Unpleasant Events, Pleasant
      Events, Sensory/Personal Contact, Food Related Activity, Social/Environmental
      Interactions, and Ritual Related Stress. These stress dimensions are highly
      relevant to the problems of autism and have not been addressed by other stress
      surveys. The information obtained from the Stress Survey can be used to plan for
      strategies to reduce the stress before it occurs or results in maladaptive
      behavior.

PMID- 11450820
TI  - Predictors and correlates of adaptive functioning in children with developmental
      disorders.
AB  - Autism is a developmental disorder marked by impairments in socialization,
      communication, and perseverative behavior and is associated with cognitive
      impairment and deficits in adaptive functioning. Research has consistently
      demonstrated that children with autism have deficits in adaptive functioning more
      severe than their cognitive deficits. This study investigates the correlates and
      predictors of adaptive functioning as measured by the Vineland Adaptive Behavior
      Scales in high- and low-functioning children with autism and their age and
      nonverbal IQ matched controls. Thirty-five 9-year-old children with high
      functioning autism (HAD) were compared with 31 age-matched children with
      developmental language disorder (DLD), and 40 9-year-old children with low
      functioning autism (LAD) were compared with 17 age-matched children with low IQ
      on adaptive functioning, IQ, autistic symptomology, and tests of language and
      verbal memory. Results indicate that both groups with autism were significantly
      impaired compared to their matched controls on Socialization and Daily Living,
      but not Communication and that these impairments were more pronounced in the HAD
      group than in the LAD group. Adaptive behavior was strongly correlated with
      autistic symptomology only in the HAD group. Regression analyses indicated that
      IQ was strongly predictive of adaptive behavior in both low-functioning groups,
      but tests of language and verbal memory predicted adaptive behavior in the higher
      functioning groups. Results suggest that IQ may act as a limiting factor for
      lower functioning children but higher functioning children are impaired by
      specific deficits, including autistic symptomology and impaired language and
      verbal memory.

PMID- 11450821
TI  - Brief report: A case of autism with interstitial deletion of chromosome 13.
AB  - A case of an 18-year-old male who meets the DSM-IV criteria for autistic disorder
      and borderline intelligence is described. Cytogenetic evaluation revealed a
      karyotype of 46, XY, del(13)(q14q22). The relevance of this case to the etiology
      of autism is discussed.

PMID- 11450822
TI  - Brief report: An assessment of stimulus generalization and contingency effects in
      functional communication training with two students with autism.

PMID- 11450823
TI  - Brief report: Lack of correlation between age of symptom onset and
      contemporaneous presentation.
AB  - The parents/guardians of 50 individuals were surveyed using a semistructured
      interview to determine the feasibility of this method and to establish ages of
      symptom onset. Thirty-eight informants were able to recall sufficient detail to
      allow categorization of the age of symptom onset. Chi-square analysis confirmed a
      significant association between investigators' categorization and informants'
      categorization. Contemporaneous presentation was indexed using Childhood Autism
      Rating Scale, the Autism Behavior Checklist, the Conners Hyperactivity Index, and
      the Ritvo-Freeman Real Life Rating Scale for Autism. No significant correlations
      were determined between any of these indices of symptom severity and age of
      symptom onset.

PMID- 11450824
TI  - Suppressed GABAergic inhibition as a common factor in suspected etiologies of
      autism.

PMID- 11450825
TI  - Re: Secretin and autism: a two-part clinical investigation.

PMID- 11450826
TI  - Adaptive behavior in children with autism.

PMID- 11450827
TI  - What is a "placebo controlled" study?

PMID- 11450828
TI  - Nurturing older dogs: attitudes and experiences of caregivers.

PMID- 11450829
TI  - A justification for urine glucose monitoring in the diabetic dog and cat.

PMID- 11450830
TI  - Clomipramine--beyond separation anxiety.

PMID- 11450831
TI  - Thunderstorm phobia in dogs: an Internet survey of 69 cases.
AB  - To learn more about predispositions for, signs, and progression of canine
      thunderstorm phobia, a survey for owners was posted on the Internet. Questions
      addressed signalment, age of onset, behavior during storms, and treatments tried.
      Sixty-nine responses were received. Herding dogs and herding crossbreeds
      accounted for the majority of dogs. Seventeen of 41 dogs with a known age of
      onset began exhibiting thunderstorm phobia <1 year of age. Various characteristic
      responses of dogs to storms were described. Improved knowledge of the
      demographics of thunderstorm phobia, its development, and presentation will
      assist in understanding the genesis and progression of the condition.

PMID- 11450832
TI  - Efficacy of amitriptyline as a pharmacological adjunct to behavioral modification
      in the management of aggressive behaviors in dogs.
AB  - The efficacy of amitriptyline as a pharmacological adjunct to behavioral
      modification in the clinical management of aggressive behaviors in dogs was
      evaluated in two phases. Twelve dogs presenting for aggressive behaviors were
      treated sequentially with amitriptyline (2 mg/kg body weight, per os [PO] bid)
      and a placebo for 4 weeks in a prospective, randomized, double-blind, placebo
      controlled trial. Standardized protocols for behavior modification were
      implemented throughout the trial. Owners maintained behavioral records and
      reported on the number of aggressive incidents as well as the dog's overall
      improvement at the end of each 4-week period. In the second phase, 27 cases of
      dogs presenting for aggressive behaviors and treated with amitriptyline were
      reviewed, and clients were contacted to record each dog's response to treatment.
      Reports were compared to those for dogs receiving behavior modification alone
      (i.e., placebo phase of prospective study). No significant difference was
      observed in the patients' responses to adjunctive amitriptyline versus behavior
      modification alone.

PMID- 11450833
TI  - Prevalence of Pneumonyssoides caninum infection in dogs in Sweden.
AB  - A prospective study of 474 dogs, 145 cats, and 66 wild red foxes submitted for
      necropsy to the Departments of Pathology at the National Veterinary Institute and
      the Swedish University of Agricultural Sciences, Uppsala, Sweden, was conducted
      to examine for the presence of Pneumonyssoides caninum, the canine nasal mite.
      Pneumonyssoides caninum (P. caninum) was found in 95 (20%) of the dogs but in
      none of the cats or foxes. The median number of P. caninum mites per infected dog
      was 13 (range, 1 to 250). Dogs older than 3 years of age were more often infected
      with P. caninum than younger dogs, and large-breed dogs were more often infected
      than small-breed dogs. No sex predisposition was found.

PMID- 11450834
TI  - Distribution, prevalence, and relative risk of filariasis in dogs from the State
      of Washington (1997-1999).
AB  - Using antigen capture and filter tests, 6,078 dogs throughout the state of
      Washington were examined for filariasis between July 1, 1997 and October 31,
      1999. In western Washington, 791 males and 901 females examined were outdoors,
      not on prophylaxis, and had traveled out of the state; 6/791 (0.8%) males and
      7/901 (0.8%) females were infected with Dirofilaria immitis (D. immitis), and one
      (0.1%) male and one (0.1%) female were infected with Dipetalonema reconditum (D.
      reconditum). There were also 392 males and 362 females examined that were
      outdoors, not on prophylaxis, and had not traveled out of western Washington. One
      (0.1%) female was infected with D. immitis, and two (0.5%) males and one (0.2%)
      female were infected with D. reconditum. In eastern Washington, 707 males and 826
      females examined were outdoors, not on prophylaxis, and had traveled out of the
      state; 9/707 (1.0%) males and 4/826 (0.5%) females were infected with D. immitis,
      and no D. reconditum was found. There were also 376 males and 412 females
      examined that were outdoors, not on prophylaxis, and had not traveled out of the
      state. Three (0.8%) males and three (0.7%) females had D. immitis. One (0.2%)
      female had D. reconditum. Distribution of D. immitis-infected, nontravel dogs in
      eastern Washington was only found between 120 degrees and 119 degrees west
      longitude in the communities of Richland, Moses Lake, Okanogan, and Omak.
      Enzootic transmission of D. immitis and D. reconditum is occurring in both
      eastern and western Washington.

PMID- 11450835
TI  - Elevated parathyroid hormone-related protein and hypercalcemia in two dogs with
      schistosomiasis.
AB  - Two adult dogs were evaluated for hypercalcemia. Diagnostic evaluation identified
      elevated parathyroid hormone-related protein (PTHrP) and presumptive humoral
      hypercalcemia of malignancy. At necropsy, schistosomiasis was diagnosed. North
      American schistosomiasis is caused by Heterobilharzia americana. Clinical
      findings may include dermatitis, coughing, diarrhea, and anorexia.
      Clinicopathological findings may include hypercalcemia, hyperglobulinemia,
      hypoalbuminemia, anemia, and eosinophilia. Diagnosis by fecal examination is
      difficult. Praziquantel or fenbendazole treatment may be curative or palliative.
      These are the first reported cases of hypercalcemia with elevated PTHrP in
      animals without diagnosed malignancy. Elevation of PTHrP has not been previously
      reported in hypercalcemic humans or in animals with granulomatous inflammation.

PMID- 11450836
TI  - Immunomodulation therapy for feline leukemia virus infection.
AB  - Clinically ill feline leukemia virus (FeLV)-infected cats, treated with
      Staphylococcus protein A (SPA) or oral interferon alpha (IFN), or both, were
      compared with cats treated with saline (SAL). Nine cats received SPA/SAL, nine
      received SPA/IFN, 10 received SAL/IFN, and eight received SAL/SAL. Twelve cats
      survived and completed the 100-week therapy. Significantly more owners of cats
      treated with SPA/SAL thought their cat's health improved during treatment
      compared to owners of cats treated with SAL/SAL (P=0.05, pair-wise comparison) or
      SPA/IFN (P=0.05, pair-wise comparison). No significant differences in body
      weight, temperature, hematocrit, red blood cell counts, mean corpuscular
      hemoglobin concentration, reticulocyte counts, white blood cell or neutrophil
      numbers, lymphocyte concentrations, bone-marrow cytopathology, FeLV status,
      survival time, activity, or appetite scores were observed. No significant
      differences in the owners' subjective assessment of their cat's health following
      treatment with SAL/IFN, SPA/IFN, or SAL/SAL were seen. Therapy with SPA as a
      single agent results in the owners' subjective impression of improved health of
      their FeLV-infected cats.

PMID- 11450837
TI  - Severe calcinosis cutis associated with treatment of hypoparathyroidism in a dog.
AB  - A 6-month-old, female border collie was referred for evaluation of hypocalcemia,
      hyperphosphatemia, fever, and painful ventral abdominal skin. She had recently
      been treated intravenously and subcutaneously (SC) with a diluted 10% calcium
      gluconate solution. The medical evaluation supported the diagnosis of primary
      hypoparathyroidism, but the subsequent hospital course was complicated by severe
      calcinosis cutis, which caused extensive skin necrosis and marked debilitation.
      This patient illustrates that administration of a calcium gluconate solution SC
      can be associated with extensive morbidity when administered to hyperphosphatemic
      patients.

PMID- 11450838
TI  - Primary hypoparathyroidism in a cat complicated by suspect iatrogenic calcinosis
      cutis.
AB  - An adult male cat presented to the Ontario Veterinary College after having a
      seizure at the humane society. The cat was diagnosed with primary
      hypoparathyroidism and was treated with calcium and vitamin D3 supplementation.
      Calcium supplementation included subcutaneous (SC) administration of diluted
      calcium gluconate according to protocols described in recent literature. Seven
      days after SC calcium administration, firm SC masses developed in the
      intrascapular area where the injections were given and in the dependent axillary
      area. These areas became raised, formed crusts, necrosed, and left scars.
      Although not histopathologically confirmed, the author postulates that this was a
      direct reaction to SC calcium gluconate administration.

PMID- 11450839
TI  - Fibrocartilaginous embolic myelopathy in miniature schnauzers.
AB  - In large- and giant-breed dogs, fibrocartilaginous embolic myelopathy (FCEM) is a
      well-recognized syndrome of acute spinal cord infarction caused by embolization
      of fibrocartilage. The miniature schnauzer is reportedly the most frequently
      affected small breed, although clinical data from only six miniature schnauzers
      with FCEM is available in the literature. The purposes of this study were to
      determine the relative frequency of FCEM compared to other causes of myelopathy
      in miniature schnauzers, to characterize the clinicopathological features of FCEM
      in 38 miniature schnauzers, and to directly compare FCEM and intervertebral disk
      herniation in miniature schnauzers with respect to age at diagnosis; gender;
      neuroanatomical localization; and progression, asymmetry, and severity of
      neurological deficits. Fibrocartilaginous embolic myelopathy was the most common
      cause of myelopathy in miniature schnauzers. Age at diagnosis, asymmetry and
      severity of neurological deficits, and lack of progression of clinical signs
      after 24 hours assisted in distinguishing FCEM from intervertebral disk
      herniation. Fibrocartilaginous embolic myelopathy-related mortality in miniature
      schnauzers was significantly lower than mortality rates reported for affected
      large and giant breeds. Only 22% of miniature schnauzers were euthanized because
      of their disease, although the vast majority of survivors failed to achieve
      complete neurological recovery.

PMID- 11450840
TI  - Intervertebral disk disease in 10 cats.
AB  - The medical records of 10 cats diagnosed with intervertebral disk disease were
      reviewed. No apparent sex or breed predilection was found. The mean age of cats
      in the study was 9.8 years. Clinical signs included back pain, difficulty
      ambulating, and incontinence. Radiographs revealed narrowed disk spaces,
      mineralized intervertebral disks, and evidence of extradural compression on
      myelography or computed tomography. All intervertebral disk herniations occurred
      in the thoracolumbar spine, with a peak incidence at the fourth to fifth lumbar
      (L4-L5) intervertebral disk space. Eight cats had Hansen's type I intervertebral
      disk herniation. Surgery was performed in seven cats. All cats judged to have an
      excellent outcome had undergone surgical decompression.

PMID- 11450841
TI  - A comparison of the Ameroid constrictor versus ligation in the surgical
      management of single extrahepatic portosystemic shunts.
AB  - Twenty-two dogs were managed surgically for a single extrahepatic portosystemic
      shunt; 12 with surgical ligation and 10 with an Ameroid constrictor. Utilization
      of the Ameroid constrictor significantly decreased surgery time to approximately
      half that of the ligation technique. A decreased intraoperative and postoperative
      complication rate was noted with the Ameroid constrictor group. Follow-up
      evaluation demonstrated comparable efficacy when comparing surgical techniques.
      The Ameroid constrictor offered a surgical occlusion technique for management of
      a single extra-hepatic portosystemic shunt that was equally effective to ligation
      while shortening surgical time and minimizing the risks that are commonly
      associated with ligation of the shunting vessel.

PMID- 11450842
TI  - Phallopexy for treatment of paraphimosis in the dog.
AB  - Three dogs with recurrent paraphimosis were surgically treated by creation of a
      phallopexy between the dorsal surface of the penis and the corresponding surface
      of the prepuce. Follow-up evaluation was performed 4 to 31 months
      postoperatively. Treatment was successful in each case, and no dog had any
      adverse sequelae.

PMID- 11450843
TI  - Clinical and genetic features of nonsyndromic autosomal dominant sensorineural
      hearing loss: KCNQ4 is a gene responsible in Japanese.
AB  - Sixteen Japanese nonsyndromic autosomal dominant sensorineural hearing loss
      (ADSNHL) families were investigated clinically as well as genetically. Most
      families showed postlingual hearing loss. Although the severity of their hearing
      loss varied, most patients showed mild-moderate sensorineural hearing loss of a
      progressive nature. Mutation analysis was performed for the MYO7A, KCNQ4, and
      GJB3 genes, which are known to be responsible for autosomal dominant
      sensorineural hearing loss. The present study reports that a mutation in KCNQ4, a
      member of a large family of potassium channel genes, was responsible for ADSNHL
      in one Japanese family.

PMID- 11450844
TI  - Characterization of the human beta4 nAChR gene and polymorphisms in CHRNA3 and
      CHRNB4.
AB  - Most neuronal nicotinic acetylcholine receptors are heteropentamers, composed of
      alpha and beta subunits. Mice lacking the alpha3 subunit and mice lacking both
      the beta2 and beta4 subunits, but not mice lacking the beta2 or beta4 subunits
      alone, have a severe phenotype characterized by megacystis, failure of bladder
      strips to contract in response to nicotine, widely dilated ocular pupils, growth
      failure, and perinatal mortality. The deficit in bladder contraction was also
      found in mice lacking only the beta4 subunit, although they did not develop
      megacystis. The major bladder phenotype resembles the human autosomal recessive
      disorder of megacystis-microcolon-hypoperistalsis syndrome (MMIHS). Based on the
      similarity of the mouse and human phenotypes, we initiated mutation analyses in
      the alpha3 and beta4 genes in MMIHS families. The human gene encoding the beta4
      subunit was fully characterized, including refinement of its mapping. Analysis of
      disease families and controls identified numerous genetic variants, including
      high-frequency polymorphisms in both CHRNA3 and CHRNB4. Although no loss-of
      function mutations have been identified to date, these genes remain strong
      candidates for involvement in MMIHS, because various mutations might be obscured
      within the complex cluster of genes. Some of the markers presented here are
      valuable tools for analysis of the role of genetic variation in responses to
      nicotine and for characterization of various dysautonomic abnormalities.

PMID- 11450845
TI  - Linkage disequilibrium and haplotype analysis among eight novel single-nucleotide
      polymorphisms in the human tissue-type plasminogen activator (t-PA) gene.
AB  - Tissue-type plasminogen activator (t-PA), a serine protease, activates the
      conversion of plasminogen to the fibrinolytic protein, plasmin. The t-PA gene,
      mapped to chromosome 8p12-p11.2, contains 14 exons. An Alu insertion/deletion
      (I/D) polymorphism in this gene has been associated with an increased risk for
      myocardial infarction. In the work reported here we sequenced 11 kilobases (kb)
      of genomic DNA from 50 normal Japanese volunteers (100 alleles), to include all
      14 exons of the t-PA gene, flanking intronic sequences, and 6kb of the 5'
      sequence. These experiments identified eight novel single-nucleotide
      polymorphisms (SNPs), in addition to the known Alu I/D polymorphism, from which
      genotypic data we constructed 12 haplotypes in the tested population. Two-way
      comparisons of SNPs and the Alu polymorphism revealed strong linkage
      disequilibrium between the Alu site and SNPs at positions 20,209 (chi2 = 92.263)
      and 27,555 (chi2 = 47.53), and between SNPs at positions 27,849 and 28,902 chi2 =
      66.331). A phylogenic tree was constructed to infer a process of genome
      construction that would reflect the sequence variations we observed. Our results
      help to explain the lack of agreement among results of various disease
      association studies in which a contribution of the human t-PA gene has been
      suspected but not always confirmed.

PMID- 11450846
TI  - Definition of a 1-Mb homozygous deletion at 9q32-q33 in a human bladder-cancer
      cell line.
AB  - We performed detailed molecular analyses of a suspected homozygous deletion on
      chromosome 9q32-q33 in a bladder-cancer cell line (KYBTDS) derived from a
      superficial papillary transitional cell carcinoma (TCC). We examined 13 sequence
      tagged site (STS) markers mapped along 9q32-q33 by polymerase chain reaction
      (PCR), and used 13 bacterial artificial chromosome (BAC)/bacteriophage P1-derived
      artificial chromosome (PAC) genomic clone probes representing these STS markers
      as probes for dual-color fluorescence in situ hybridization (FISH) analyses to
      define the deleted region cytogenetically and at the molecular level. Southern
      blotting confirmed the findings. This combination of techniques revealed that the
      homozygous deletion in the KYBTDS cell line involved less than 1 megabase of DNA,
      flanked by markers A003P42 and SGC33380. This interval overlaps part of a common
      region of deletion observed in a number of primary bladder cancers; moreover, the
      DNA sequence within the 1-Mb segment corresponds to part of a YAC genomic clone
      that encompasses a putative tumor suppressor gene, DBCCR1.

PMID- 11450847
TI  - Chromosomal localization, structure, single-nucleotide polymorphisms, and
      expression of the human H-protein gene of the glycine cleavage system (GCSH), a
      candidate gene for nonketotic hyperglycinemia.
AB  - Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism caused by
      deficiency in the glycine cleavage system (GCS); this system consists of four
      individual constituents, P-, T-, H-, and L-proteins. Several mutations have been
      identified in P- and T-protein genes, but not in the H-protein gene (GCSH),
      despite the presence of case reports of H-protein deficiency. To facilitate the
      mutational and functional analyses of GCSH, we isolated and characterized a human
      p1-derived artificial chromosome (PAC) clone encoding GCSH. GCSH spanned 13.5kb
      and consisted of five exons. Using the PAC clone as a probe, we mapped GCSH to
      chromosome 16q24 by fluorescence in situ hybridization. The transcription
      initiation site was determined by the oligonucleotide-cap method, and potential
      binding sites for several transcriptional factors were found in the 5' upstream
      region. Direct sequencing analysis revealed five single-nucleotide polymorphisms.
      The expression profiles of P-, T-, and H-protein mRNAs were studied by dot-blot
      analysis, using total RNA from various human tissues. GCSH was expressed in all
      29 tissues examined, while T-protein mRNA was detected in 27 of the 29 tissues.
      In contrast, the P-protein gene was expressed in a limited number of tissues,
      such as liver, kidney, brain, pituitary gland, and thyroid gland, suggesting
      distinct transcriptional regulation of each GCS constituent.

PMID- 11450848
TI  - Catalog of 434 single-nucleotide polymorphisms (SNPs) in genes of the alcohol
      dehydrogenase, glutathione S-transferase, and nicotinamide adenine dinucleotide,
      reduced (NADH) ubiquinone oxidoreductase families.
AB  - An approach based on development of a large archive of single-nucleotide
      polymorphisms (SNPs) throughout the human genome is expected to facilitate large
      scale studies to identify genes associated with drug efficacy and side effects,
      or susceptibility to common diseases. We have already described collections of
      SNPs present among various genes encoding drug-metabolizing enzymes. Here we
      report SNPs for such enzymes at additional loci, including 8 alcohol
      dehydrogenases, 12 glutathione S-transferases, and 18 belonging to the NADH
      ubiquinone oxidoreductase family. Among DNA samples from 48 Japanese volunteers,
      we identified a total of 434 SNPs at these 38 loci: 27 within coding elements, 52
      in 5' flanking regions, five in 5' untranslated regions, 293 in introns, 20 in 3'
      untranslated regions, and 37 in 3' flanking regions. The ratio of transitions to
      transversions was approximately 2.1 to 1. Among the 27 coding SNPs, 13 were
      nonsynonymous changes that resulted in amino acid substitutions. Our collection
      of SNPs derived from this study should prove useful for investigations designed
      to detect associations between genetic variations and common diseases or
      responsiveness to drug therapy.

PMID- 11450849
TI  - Gene fusion involving HMGIC is a frequent aberration in uterine leiomyomas.
AB  - HMGIC, a high-mobility-group protein gene encoding an architectural transcription
      factor, was recently identified as the target of gene fusion in a variety of
      human benign mesenchymal tumors; some of these events were chromosomal
      translocations involving 12q13-15. HMGIC consists of three DNA-binding domains
      (encoded by exons 1-3), a spacer, and an acidic carboxyl-terminal regulatory
      domain (exons 4-5). To determine the spectrum and nature of the aberrations in
      uterine myomas in Japanese patients, we systematically examined the tumors of 45
      patients for all possible types of gene fusions involving HMGIC, by means of 3'
      rapid amplification of cDNA ends (RACE) and reverse transcriptase-polymerase
      chain reaction (RT-PCR) experiments. HMGIC gene fusions were found in 16 (36%) of
      the tumors; aberrant splicings to five cryptic sequences located in introns of
      the HMGIC gene were found in 11 of these cases, and translocations causing
      juxtaposition to other genes, such as COX6C and RA D51B, were found in 5. In all
      fusion transcripts, the first two or three exons of HMGIC were fused to ectopic
      sequences. Our results suggest that a fusion event, resulting in the separation
      of the DNA-binding domains of HMGIC from the spacer and the acidic carboxyl
      terminal regulatory domain, is a common tumorigenic mechanism in the development
      of uterine myomas.

PMID- 11450850
TI  - The genomic structure and expression of MJD, the Machado-Joseph disease gene.
AB  - Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder
      that is clinically characterized by cerebellar ataxia and various associated
      symptoms. The disease is caused by an unstable expansion of the CAG repeat in the
      MJD gene. This gene is mapped to chromosome 14q32.1. To determine its genomic
      structure, we constructed a contig composed of six cosmid clones and eight
      bacterial artificial chromosome (BAC) clones. It spans approximately 300kb and
      includes MJD. We also determined the complete sequence (175,330bp) of B445M7, a
      human BAC clone that contains MJD. The MJD gene was found to span 48,240bp and to
      contain 11 exons. Northern blot analysis showed that MJD mRNA is ubiquitously
      expressed in human tissues, and in at least four different sizes; namely, 1.4,
      1.8, 4.5, and 7.5kb. These different mRNA species probably result from
      differential splicing and polyadenylation, as shown by sequences of the 21
      independent cDNA clones isolated after the screening of four human cDNA libraries
      prepared from whole brain, caudate, retina, and testis. The sequences of these
      latter clones relative to the MJD gene in B445M7 indicate that there are three
      alternative splicing sites and eight polyadenylation signals in MJD that are used
      to generate the differently sized transcripts.

PMID- 11450851
TI  - Single nucleotide polymorphisms of RXRA encoding retinoid X receptor alpha.
AB  - Retinoic X receptor alpha (RXRA), encoded by RXRA, plays a key role in
      development and metabolism, specifically in adipocyte biology, glucose
      homeostasis, and intestinal cholesterol balance. RXRA is also a positional
      candidate gene for Berardinelli-Seip congenital lipodystrophy. We report the
      systematic screening of RXRA coding regions by genomic DNA sequencing, which has
      resulted in the identification of three novel single-nucleotide polymorphisms.

PMID- 11450852
TI  - Two mutations of the Gsalpha gene in two Japanese patients with sporadic
      pseudohypoparathyroidism type Ia.
AB  - Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical
      hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the
      phenotype of Albright hereditary osteodystrophy (AHO), including short stature,
      obesity, round face, brachydactyly, and subcutaneous ossification. This disease
      is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory
      regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon
      88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were
      identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon
      4 at codon 88 in the first patient produced a premature stop codon, resulting in
      the truncated protein. The second patient had a previously reported R231H
      mutation. Because this amino acid is located in a region, switch 2, that is
      thought to interact with the betagamma subunit of Gsalpha protein, this mutation
      may impair Gs protein function. We report here one novel Gsalpha mutation, and
      note that mutations in Japanese patients with PHP-Ia are probably heterogeneous.

PMID- 11450853
TI  - Enzymes and operons mediating xenobiotic degradation in bacteria.
AB  - Aromatic hydrocarbons constitute a major group of environmental pollutants.
      Bioremediation appears to be the only viable alternative for large-scale
      decontamination. A number of bacteria have been identified that can degrade a
      variety of xenobiotics. Extensive studies of the enzymes and genes involved in
      degradation of aromatic hydrocarbons have revealed that the degradative enzymes
      could be broadly grouped into two major categories, peripheral and ring-cleavage
      enzymes. The peripheral enzymes are the ones that catabolize the pollutants
      initially to a metabolite that is further degraded. A majority of peripheral
      enzymes are oxygenases that hydroxylate the aromatic compounds, rendering them
      susceptible to the enzymes of ring-cleavage pathway. The genes of ring-cleavage
      enzymes have been shown to be highly conserved between different bacterial
      species. Presently, a number of constraints limit the use of available strains
      for efficient bioremediation. This review describes the enzymes and genes
      involved in xenobiotic degradation and underscores the importance of
      understanding the expression and regulation of genes encoding peripheral enzymes
      and their intelligent manipulation using recombinant DNA technology for efficient
      degradation of aromatic compounds.

PMID- 11450854
TI  - Environmental and food safety aspects of Escherichia coli O157:H7 infections in
      cattle.
AB  - The presence of E. coli O157:H7 in cattle illustrates the complex, interrelated
      nature of the environment, livestock production practices, food safety, and the
      science of microbiology, particularly microbial ecology. Enterohemorrhagic E.
      coli, including E. coli O157:H7, can cause severe human diseases that can be
      debilitating and life threatening. Cattle are currently considered to be the
      definitive source for E. coli O157:H7 in the food supply, but this view may be
      simplistic and incomplete. E. coli O157:H7, appears widespread among U.S. cattle
      herds, while individual animal prevalence is low and transient. Most individual
      animals appear to be a transient reservoir for E. coli O157:H7 although the issue
      of carrier animals still remains unresolved. Epidemiological studies of the
      cattle production system have not clearly identified risk factors or management
      practices that affect E. coli O157:H7 prevalence in cattle feces. The problem of
      E. coli O157:H7 increases during the summer and fall months, but the
      environmental factors that contribute to this increase are poorly understood.
      Possible environmental factors that may influence E. coli O157:H7 shedding in
      cattle include livestock feed and waste handling practices as well as insects and
      microbial interactions in soil and water. Studies of E. coli O157:H7 ecology in
      cattle and the environment have been limited, but they suggest that a
      consideration of other independent, environmental sources of this microbe seems
      appropriate. The natural ecology of cholera may serve as a useful environmental
      model for pursuing additional environmental research on the occurrence and
      transmission of E. coli O157:H7 in nature.

PMID- 11450855
TI  - A metabolic node in action: chorismate-utilizing enzymes in microorganisms.
AB  - The shikimate pathway has been described as a metabolic tree with many branches
      that led to the synthesis of an extensive range of products. This pathway is
      present only in bacteria, fungi, and plants. While there is only little
      difference in the sequence of the chemical reactions of the pathway, significant
      differences exist in terms of organization and regulation. In the main trunk of
      the shikimate pathway, D-erythrose 4-phosphate and phosphoenolpyruvate are
      converted via shikimate to chorismate. Chorismate is the common precursor for the
      biosynthesis of the aromatic amino acids, phenylalanine, tyrosine, and
      tryptophan, but also for other products as diverse as folate cofactors, benzoid
      and naphthoid coenzymes, phenazines, and siderophores. Five chorismate-utilizing
      enzymes have been characterized in microorganisms: chorismate mutase,
      anthranilate synthase, aminodeoxychorismate synthase, isochorismate synthase, and
      chorismate pyruvate-lyase. In this review these enzymes are discussed in terms of
      the corresponding gene structures and regulation, nucleotide and protein
      sequences, protein structures, and reaction mechanisms. The main emphasis is on
      transcriptional and posttranslational regulatory mechanisms, in view of how a
      microbial cell exploits its chorismate pool in diverse anabolic pathways.
      Comparison of the chorismate-utilizing enzymes has shown that some of them share
      sequence similarity, suggesting divergent evolution and commonality in reaction
      mechanisms. However, other chorismate-utilizing enzymes are examples of
      convergent evolution toward similar reaction capabilities.

PMID- 11450856
TI  - Novel strategies for intervention targeted at mycobacterial persistence.
AB  - Effective global control of tuberculosis is likely to require intervention at
      multiple points in the course of infection. In addition to existing approaches
      based on treatment of active disease and preventive vaccination of unexposed
      individuals, current research on the biology of mycobacterial persistence
      suggests the potential for the development of novel disease-control strategies
      targeted at infected asymptomatic populations.

PMID- 11450857
TI  - Detection of active tuberculosis by an MPB-64 transdermal patch: a field study.
AB  - The mycobacterial antigen MPB-64 was formulated for delivery in a transdermal
      patch and used as a diagnostic skin test reagent to detect active tuberculosis
      (TB) in patients attending a clinic in Manila, The Philippines. The MPB-64
      Transdermal Patch was applied to 62 patients, 49 with sputum-positive active
      disease and 13 who had completed TB chemotherapy, and to 28 non-TB but tuberculin
      positive controls. The results were read at 72 h. The sensitivity of the
      Transdermal Patch was 87.8%, with an efficacy of 92.9% and a specificity of 100%.
      The 13 TB patients who had completed 6 months of TB chemotherapy showed different
      reactions to the MPB64 patch test: those who had completed chemotherapy < 4
      months before testing were positive; 50% of patients who completed chemotherapy 5
      months previously were positive; and those who had completed chemotherapy 7 and 8
      months before were negative. All the non-TB controls with positive tuberculin
      tests were negative to the MPB-64 Transdermal Patch, even at the highest protein
      dose tested. This test may be a useful method to distinguish active TB patients
      from TB-infected but asymptomatic individuals. Moreover, the MPB64 Transdermal
      Patch may be useful to monitor successful chemotherapy.

PMID- 11450858
TI  - Interaction of Staphylococcus epidermidis from infected hip prostheses with
      neutrophil granulocytes.
AB  - This study focuses on the interaction of Staphylococcus epidermidis isolated from
      granulation tissue covering infected hip prostheses and neutrophil granulocytes.
      Bacterial strains isolated from normal flora were used as controls. The bacteria
      were well characterized with routine methods and further characterized with
      random amplified polymorphic DNA analyses and slime tests. Phagocytosis and
      chemiluminescence (CL) assays were used in the neutrophil interaction studies.
      The prostheses strains were ingested to a lesser extent than strains from normal
      flora (p < or = 0.001). There was no significant difference between the
      prostheses strains and the normal flora strains in terms of total CL response.
      However, the extracellular CL response from the neutrophils was lower in
      comparison with the normal flora when interacting with the prostheses strains.
      The results of this study support the notion that S. epidermidis strains isolated
      from infected hip prostheses have an enhanced capacity to resist phagocytosis and
      that most of these strains elicit a reduced inflammatory response, measured as
      the production of extracellular oxidative metabolites from the neutrophils,
      compared to normal flora.

PMID- 11450859
TI  - The impact of environmental Pseudomonas aeruginosa genotypes on skin infections
      in occupational saturation diving systems.
AB  - Skin infection caused by Pseudomonas aeruginosa is the most frequent health
      problem associated with occupational saturation diving on the Norwegian
      continental shelf. In the course of 14-y surveillance of infection and
      environmental control in occupational offshore saturation diving systems, a
      collection of approximately 1000 P. aeruginosa isolates has been amassed.
      Retrospective genomic analyses using restriction enzyme fragmentation and pulsed
      field gel electrophoresis have identified 24 of 76 environmental P. aeruginosa
      genotypes as being of significance for single infections, outbreaks of infections
      and recurrent skin infections in occupational diving systems. In addition, these
      genomic analyses have made it possible to separate outbreaks of infection into
      outbreaks with 1 single genotype and clusters of infections where different
      genotypes are involved. We conclude that the established, assumed diver-to-diver
      contagion vector ought to be replaced by a environmental contagion vector as the
      most likely vector within these specific occupational environments. Furthermore,
      consecutive presence of the frequent environmental/infectious genotypes demands
      specific improvement of infection prevention and control in these systems.

PMID- 11450860
TI  - Drug resistance of Salmonella strains isolated from community infections in
      Ankara, Turkey, 1993-99.
AB  - 160 Salmonella strains were isolated from children at the paediatrics department
      of Ankara University. 48.1% of the isolates were Salmonella enteritidis, 41.9%
      Salmonella typhimurium and 10% other serotypes. For the analysis of data, the
      study period was divided into 2 periods: 1993-95 and 1996-99. A decline in the
      isolation rate of S. typhimurium (from 63.1% to 30.1%) and rapid rise in S.
      enteritidis (from 31.6% to 57.3) was observed during the review period. However,
      for S. typhimurium isolates, the 5-drug (ampicillin, chloramphenicol,
      streptomycin, tetracycline and sulfonamides) pattern of resistance was increased
      from 13.5% to 38.7% in the second period. Since S. enteritidis and 5-drug
      resistant S. typhimurium have also increased in other countries, their pandemic
      spread in humans indicates the continuing importation and exportation of these
      pathogens.

PMID- 11450861
TI  - Serological and epidemiological analysis of the prevalence of Bartonella spp.
      antibodies in Swedish elite orienteers 1992-93.
AB  - The emergence of the popular, physically demanding and highly nature-interactive
      sport of orienteering was marked in Sweden by an elevated rate of sudden
      unexpected cardiac deaths in young competitors during the years 1979-92, with a
      common underlying cause or causes suspected. Subsequently, sera were collected
      during 1992-93 from the elite segment of orienteers holding a nationally ranked
      position, and a survey compiling various epidemiological data was performed. In
      this study, a total of 1136 sera were analyzed by indirect-fluorescent antibody
      assay for the presence of IgG antibodies against 3 Bartonella spp.: B. henselae,
      B. elizabethae and B. quintana. In total, 31% (355/1136) were seropositive for at
      least 1 species of Bartonella, with titers ranging up to 1/512; 350/1136 (31%)
      had antibodies against B. elizabethae, 34/1136 (3.0%) against B. henselae and
      16/1136 (1.4%) against B. quintana. Males and females showed equal rates of 31%
      seropositisity to Bartonella spp. (males 241/766; females 114/370). In
      comparison, 322 time-matched sera from healthy blood donors had antibodies to
      Bartonella spp. in 6.8% of cases (p < 0.001). The observed high prevalence of
      Bartonella spp. antibodies found in Swedish elite orienteers may be indicative of
      a connection with risk factors for the development of myocarditis and sudden
      unexpected cardiac death.

PMID- 11450862
TI  - Subacute bartonella infection in Swedish orienteers succumbing to sudden
      unexpected cardiac death or having malignant arrhythmias.
AB  - During the period 1979-92, an increasing number of sudden unexpected cardiac
      deaths (SUCD) occurred in young, Swedish, male elite orienteers. Myocarditis was
      the most common diagnosis in the 16 victims, and in 4 cases was also associated
      with fatty infiltration mimicking arrhythmogenic right ventricular cardiomyopathy
      (ARVC). Tissues from autopsies of 5 orienteers were tested for Bartonella by PCR
      targeting the gltA (citrate-synthase) gene. The products were then sequenced.
      Antibodies to B. henselae, B. quintana and B. elizabethae were measured by
      indirect fluorescence antibody assay. Bartonella spp. DNA was detected in the
      hearts of 4 deceased orienteers, and in the lung of a fifth deceased case. The
      sequences were close to B. quintana in 2 cases and identical to B. henselae in 3.
      Four of these 5 cases, as well as 2 additional cases of elite orienteers with
      ARVC, indicated antibodies to Bartonella. It is suggested that Bartonella-induced
      silent subacute myocarditis, eventually leading to electric instability, caused
      the increased SUCD rate among the Swedish orienteers. It is further suggested
      that Bartonella infection may be a major pathogenetic factor in the development
      of ARVC-like disease. Although the mode of transmission is unknown, both
      zoonotic/vector-borne and parenteral person-to-person transmission may be
      involved.

PMID- 11450863
TI  - Birth outcome and risk of neonatal hypoglycaemia following in utero exposure to
      pivmecillinam: a population-based cohort study with 414 exposed pregnancies.
AB  - Concerns have been raised as to the safety of using pivaloyl-conjugated beta
      lactam antibiotics during pregnancy as they cause carnitine depletion.
      Restrictions have been recommended in some Scandinavian countries as drug-induced
      carnitine depletion could constitute a risk to the developing foetus. One of
      these drugs, pivmecillinam, is widely used against urinary tract infections but
      few data exist concerning its safety in pregnancy. In a cohort study, we compared
      the prevalences of congenital abnormalities, pre-term delivery, low birth weight,
      low Apgar score and neonatal hypoglycaemia in the offspring of 414 women who had
      at least 1 prescription for pivmecillinam redeemed during pregnancy with those of
      the offspring of 7472 pregnant women for whom no drugs were prescribed during
      pregnancy. The prevalence of congenital abnormalities was 1.7% among 119 infants
      exposed in the first trimester and 3.7% among the reference group [odds ratio
      (OR) 0.46; 95% confidence interval (CI) 0.11-1.86]. We found no significantly
      increased risks in either pre-term delivery (OR 0.91, 95% CI 0.11-1.86), low
      birth weight (OR 0.57, 95%, CI 0.23-1.41), low Apgar score (OR 2.32, 95% CI 0.30
      18.16) or hypoglycaemia (OR 0.73, 95% CI 0.18-3.00) that were induced by
      carnitine depletion. No significantly increased risk in adverse birth outcome was
      therefore found in women treated with pivmecillinam.

PMID- 11450864
TI  - Outbreak caused by tobramycin-resistant Pseudomonas aeruginosa in a bone marrow
      transplantation unit.
AB  - Between May and August 1995, 5 patients in a bone marrow transplantation (BMT)
      ward developed bacteremia caused by Pseudomonas aeruginosa resistant to
      tobramycin (TRPA). Previously, isolates of TRPA had been limited to patients who
      were treated in 1 intensive care unit (ICU) of this tertiary care teaching
      hospital in Helsinki, Finland. To study whether the outbreak was caused by a
      single or multiple strains of P. aeruginosa, 102 isolates of TRPA from clinical
      samples obtained from different hospital units and 22 isolates obtained from the
      hospital environment were characterized by pulsed-field gel electrophoresis. All
      isolates from hematological patients produced 1 unique fragment pattern, which
      was also isolated from 3 ICU patients before the BMT ward outbreak began as well
      as from 5 shower heads in the BMT ward. The outbreak in the BMT ward was
      successfully controlled by eradicating the probable environmental source-
      contaminated hand showers--but the endemic infections continued in the ICU.

PMID- 11450865
TI  - High mortality and severe immunosuppression in hospitalized patients with
      pulmonary tuberculosis and HIV-2 infection in Guinea-Bissau.
AB  - The aim of this study was to prospectively compare the clinical outcomes in HIV-2
      infected and HIV-negative patients with culture-confirmed pulmonary tuberculosis,
      evaluate immunological changes and investigate risk factors for decreased
      survival in HIV-2-positive subjects. From 1994 to 1997, 127 consecutive patients
      with pulmonary tuberculosis were included at the Raoul Follereau Hospital in
      Bissau, the capital of Guinea-Bissau. All subjects were initially hospitalized,
      and then followed to the end of the 8-month treatment period. CD4 T-lymphocyte
      counts were determined by flow cytometry before, during and at the end of the
      treatment period. The prevalences of HIV-1, HIV-2 and HIV-1/HIV-2 dual reactivity
      were 8.7%, 23.6% and 9.4%, respectively (95% confidence intervals 3.8-13.6, 16.2
      31.0 and 4.4-14.5, respectively). The mortality rate during the study period was
      significantly higher in HIV-2-positive (p < 0.01) and HIV-1/HIV-2 dually reactive
      (p < 0.01) patients than in HIV-negative individuals (52.9, 83.3 and 8.7 per 100
      person-years, respectively). In HIV-1-positive patients the mortality rate was
      30.8/100 person-years (p = NS). Baseline total CD4 cell counts were 213, 104, 235
      and 624 x 10(6)/l (% CD4 = 17, 15, 20 and 40) among HIV-1-, HIV-2- and HIV-1/HIV
      2-positive and HIV-negative subjects, respectively. The median rates of change
      per year of total CD4 cell counts in HIV-2-positive and HIV-negative subjects
      were 66 and 340 x 10(6)/l, respectively (interquartile ranges -78-249 and 21
      624). In conclusion, we found a significantly higher mortality rate in HIV-2
      positive compared to HIV-negative individuals. Baseline CD4 cell counts were
      markedly suppressed and similar in all 3 HIV-positive groups, and in a
      multivariate logistic regression analysis a value of CD4 percentage of < 10 was
      shown to be an independent predictor of decreased survival in HIV-2-infected
      subjects.

PMID- 11450866
TI  - Trends in HCV prevalence among injecting drug users in Glasgow and Edinburgh
      during the era of needle/syringe exchange.
AB  - In 1998, we reported that anti-HCV prevalence among injectors from Glasgow had
      declined between 1990 and 1995. We set out to ascertain if the anti-HCV
      prevalence among injectors from Edinburgh had declined similarly during this
      period and if there had been any trend in prevalence among injectors from both
      cities since 1995. Residual sera from both cities' injecting drug users who had
      undergone named HIV testing were identified, linked to age band and gender
      information and tested anonymously for anti-HCV. Among Edinburgh's injectors,
      significant (p < 0.0001) decreases in anti-HCV prevalence from 69% (1989/90) to
      13% (1997) and from 80% (1989/90) to 54% (1997) were seen in those aged < 25 y
      and > or = 25 y, respectively. Among Glasgow's injectors, a significant (p <
      0.0001) decrease in prevalence from 91% (1990) to 43% (1997) was seen only among
      those aged < 25 y. Of both cities' 15-19 y olds, sampled during 1995-97, 17%
      (24/139) were anti-HCV-positive. The findings suggest that the incidence of HCV
      among young injectors continued to decrease during the 1990s--the era of
      needle/syringe exchange and other interventions--but is still too high. Further
      investigative and preventive work is required.

PMID- 11450867
TI  - Elevated serum levels of interleukin-10 in children with acute rubella infection.
AB  - Interleukin-10 (IL-10) is known to be an anti-inflammatory cytokine which
      inhibits cell growth and cytokine production of both Th1 and Th2 cells. Using a
      human IL-10 ELISA kit we investigated whether serum IL-10 levels increased during
      the acute and convalescent stages in 45 children with rubella infections. Serum
      levels of IL-10 were markedly elevated in rubella patients during the acute
      stage, compared with those at the convalescent stage and those in healthy age
      matched children (mean +/- SEM): 18.5 +/- 3.4 vs. 6.0 +/- 0.6 vs. 7.9 +/- 1.3
      pg/ml. IL-10 levels determined 5 d after the onset of the disease had returned to
      the normal range. In patients with rubella, there were significant negative
      correlations between serum IL-10 levels and both rubella virus-specific IgM and
      IgG antibodies. These findings suggest that IL-10 may play a role in the
      pathogenesis of acute rubella infections.

PMID- 11450868
TI  - Early bactericidal activity of amoxicillin in combination with clavulanic acid in
      patients with sputum smear-positive pulmonary tuberculosis.
AB  - The early bactericidal activity (EBA) of an antituberculosis agent is the rate of
      decrease in viable colony-forming units (CFU) per milliliter of sputum during the
      first 2 d of treatment of patients with previously untreated smear-positive
      pulmonary tuberculosis. The objective of this open randomized study was to
      evaluate the EBA of the combination of amoxicillin 3 g and clavulanic acid 750
      mg. Ten patients with a mean age of 34 y and a mean weight of 56 kg received
      amoxicillin/clavulanic acid and 5 patients with a mean age of 34 y and a mean
      weight of 57 kg received no drug. In the patients receiving 1 dose of
      amoxicillin/clavulanic acid daily for 2 d the mean log10CFU/ml of sputum before
      treatment was 6.7402 (SD 0.539) and after 2 d of treatment 6.7046 (SD 0.609); the
      corresponding values in patients receiving no drug were 6.7823 (SD 0.563) and
      6.7502 (SD 0.673), respectively. The EBA of 0.018 (SD 0.130) in patients
      receiving amoxicillin/clavulanic acid did not differ significantly from that of
      0.016 (SD 0.069) in patients receiving no drug. It is unlikely that the
      combination of amoxicillin/clavulanic acid has an important place in the
      treatment of tuberculosis with the exception of those patients with multidrug
      resistant tuberculosis who are otherwise therapeutically destitute.

PMID- 11450869
TI  - Pacemaker endocarditis: report of 2 cases.
AB  - Two cases of endocarditis due to placement of a pacemaker are reported. In both
      cases administration of intravenous antibiotic and removal of the entire pacing
      system was successful.

PMID- 11450870
TI  - Rahnella aquatilis bacteremia in a patient with relapsed acute lymphoblastic
      leukemia.
AB  - Rahnella aquatilis infections are rare. We report the case of a 46-y-old African
      American male with relapsed acute lymphoblastic leukemia who had R. aquatilis
      bacteremia after beginning reinduction chemotherapy. He was treated for 4 weeks
      with piperacillin-tazobactam and gentamicin. He recovered from the infection and
      had an allogenic bone marrow transplant a month later.

PMID- 11450871
TI  - The effects of inadvertent intramuscular injection of BCG vaccine.
AB  - We report on a case of inadvertent intramuscular injection of BCG vaccine into an
      already tuberculin-sensitive individual which resulted in a severe and prolonged
      local reaction. There is no consensus on the best management of this
      complication, although in this case healing appeared to be hastened by anti
      tuberculous chemotherapy.

PMID- 11450872
TI  - Hypersensitivity syndrome (DRESS) and meningoencephalitis associated with
      nevirapine therapy.
AB  - The DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is a
      serious condition that has been reported in association with various drugs, such
      as allopurinol, sulfonamides and aromatic anticonvulsants. Recently the condition
      has been described in HIV-infected patients taking antiretroviral agents. We
      report the first case, to our knowledge, of DRESS syndrome complicated by
      meningoencephalitis associated with nevirapine therapy.

PMID- 11450873
TI  - The impact of norfloxacin, ciprofloxacin and ofloxacin on human gut colonization
      by Candida albicans.
AB  - We studied gastrointestinal (GI) colonization by Candida albicans in patients
      receiving oral norfloxacin, ciprofloxacin or ofloxacin as monotherapy for urinary
      tract infections. Quantitative stool cultures for C. albicans were performed
      before, at the end and 1 week after the end of treatment. All 3 quinolones
      increased GI colonization by C. albicans. Ciprofloxacin caused the highest
      increase, which was not statistically significant.

PMID- 11450874
TI  - Influence of operator orientation on relative organizational mapping and spatial
      compatibility.
AB  - Following up on a study by Worringham and Beringer (1989) that examined the
      influence of operator orientation on visual-motor performance, Experiment 1
      employed a choice reaction time paradigm in which participants had to make rapid,
      discrete movements with a lever in response to a discrete stimulus. In Experiment
      2, participants had to synchronize rhythmic movements with an oscillating visual
      display. Operator orientation with respect to stimulus display and response array
      locations was varied to examine the influence of global spatial relations.
      Display orientation was varied to examine the influence of spatial configuration.
      Mapping rules were varied to examine the effects of spatial mapping. In
      Experiment 1, the spatial mapping that yielded faster responses was dependent
      upon the stimulus display-response array configuration and the global relation.
      Under a parallel configuration, participants appeared to code the spatial aspects
      of the stimulus display and response in a manner that was unaffected by the
      global spatial relation. Under an orthogonal configuration, spatial mapping
      effects were dependent upon the global relation. In Experiment 2, the global
      spatial relation did not have an impact on the uniformity of co-ordination under
      different configuration or mapping conditions. Spatial configuration influenced
      whether or not differences between spatial mapping rules emerged. Together, the
      results speak to the relative nature of stimulus-response coding that underlie
      compatibility phenomena. In addition, the results have potential importance for
      the design of human-machine systems that allow flexibility in operator
      orientation.

PMID- 11450875
TI  - Characterization of the metabolic demands of simulated shipboard Royal Navy fire
      fighting tasks.
AB  - The purpose of this study was to quantify the metabolic demand of simulated
      shipboard fire-fighting procedures currently practised by men and women in the
      Royal Navy (RN) and to identify a minimum level of cardiovascular fitness
      commensurate with satisfactory performance. Thirty-four males (M) and 15 females
      (F) volunteered as subjects for this study (n=49). Maximal oxygen uptake (VO2max)
      and heart rate (fcmax) of each subject was assessed during a standardized
      treadmill test. During the main trials, volunteers were randomly assigned to
      complete several 4-min simulated shipboard fire-fighting tasks (boundary cooling
      (BC), drum carry (DC), extinguisher carry (EC), hose run (HR), ladder climb
      (LC)), at a work rate that was endorsed as a minimum acceptable standard. Heart
      rate (fc) and oxygen uptake (VO2) were recorded at 10-s intervals during rest,
      exercise and recovery. Participants completed all tasks within an allocated time
      with the exception of the DC task, where 11 subjects (all females) failed to
      maintain the endorsed work rate. The DC task elicited the highest (p<0.01) group
      mean peak metabolic demand (PMD) in males (43 ml min(-1) kg(-1)) and females (42
      ml min(-1) kg (-1)) who were able to maintain the endorsed work rate. The BC task
      elicited the lowest PMD (23 ml min(-1) kg(-1)), whilst the remaining three tasks
      elicited a remarkably similar PMD of 38-39 ml min(-1) kg(-1). The human endurance
      limit while wearing a self-contained breathing apparatus (SCBA) dictates that RN
      personnel are only able to fire-fight for 20-30 min, while wearing a full fire
      fighting ensemble (FFE) and performing a combination of the BC, HR and LC tasks,
      which have a group mean metabolic demand of 32.8 ml min(-1) kg(-1). Given that in
      healthy subjects fire-fighting can be sustained at a maximum work intensity of
      80% VO2max when wearing SCBA for this duration, it is recommended that all RN
      personnel achieve a VO2max of 41 ml min(-1) kg(-1) as an absolute minimum
      standard. Subjects with a higher VO2max than the above quoted minimum are able to
      complete the combination of tasks listed with greater metabolic efficiency and
      less fatigue.

PMID- 11450876
TI  - Comparison of intradiscal pressures and spinal fixator loads for different body
      positions and exercises.
AB  - Loading of the spine is still not well understood. The most reliable results
      seemed to come from the intradiscal pressure measurements from studies by
      Nachemson, 1966. A new similar study by Wilke et al. (1999) complemented the
      present study and confirmed some of the earlier data, although it contradicted
      others. The new data did not confirm that the load on the spine is higher in
      sitting compared with standing and did not find distinct differences between
      positions in which subjects were lying down. The objective of this paper was to
      compare results from two independent in vivo studies (applying different methods)
      to provide information about spinal loading. In one of these studies (Wilke
      1999), intradiscal pressure was measured in one volunteer in different postures
      and exercises, and in the other study (Rohlmann et al. 1994) the loads on an
      internal spinal fixation device (an implant for stabilising unstable spines) were
      determined in 10 patients. The absolute values of the results from both studies
      were normalized and compared for many body positions and dynamic exercises. The
      relative differences in intradiscal pressure and flexion bending moments in the
      fixators corresponded in most cases. Both studies showed slightly lower loads for
      sitting than for standing and comparatively low loads in all lying positions.
      High loads were measured for jogging, jumping on a trampoline and skipping.
      Differences between trends for intradiscal pressure and for flexion bending
      moments in the fixators were found when the load was predominantly carried by the
      anterior spinal column, as during flexion of the upper part of the body or when
      lifting and carrying weights. The combination of the results from these two
      methods may improve the understanding of the biomechanical behaviour of the
      lumbar spine and may be used to validate models and theories of spinal loading.

PMID- 11450877
TI  - Torque and EMG in isometric graded flexion-rotation and extension-rotation.
AB  - The main objective of the study was to measure the magnitude and pattern of
      electromyographic (EMG) activity of the trunk muscles in combined motions of
      flexion-rotation and extension-rotation. Another objective of the study was to
      determine the torque-EMG Root Mean Square (RMS) relationship in these activities
      for predictive purposes. Nineteen normal young adult subjects who met the
      inclusion criteria were fitted with 12 pairs of surface electrodes on their
      external and internal oblique, rectus abdominis, latissimus dorsi, and erector
      spinae muscles at T10 and L3 levels bilaterally. Using a Posture Stabilizing
      Platform (PSP) they were fixed in 40 degrees flexed and 40 degrees right rotated
      trunk postures. From this posture subjects attempted an isometric extension
      rotation and flexion-rotation in the plane defined by the asymmetrical postural
      axis in the plane of rotation of the assumed posture. Contractions of 25, 50 and
      75% of the previously measured maximal voluntary contraction (MVC) were attempted
      using a Static Dynamic Strength Tester (SDST) and force monitor attached by a
      steel cable to a rigid thoracic harness worn by the subjects. The data were
      acquired at 1 kHz. Descriptive statistics were calculated and ANOVA, correlation
      and regression analyses were carried out. With linear increase in flexion
      rotation and extension-rotation torque, the magnitude of total EMG output
      increased exponentially. In flexion-rotation the EMG magnitude of all muscles
      increased with increasing grades of contraction (% of MVC). However, in
      proportional terms, the magnitude of erector spinae EMG declined. In extension
      rotation there was a reversal of roles between the ventral and dorsal muscles
      compared to the flexion-rotation. For the two genders, all muscles and grades of
      contractions were significantly different from each other (p<0.01). There was a
      significant but modest correlation between EMG and torque (r = 0.25 to 0.54;
      p<0.01). The regressions were significant (p<0.01) and explained up to 74% of the
      variance in torque. The flexion-rotation and extension-rotation torques can be
      predicted with only a moderate accuracy.

PMID- 11450878
TI  - Necessary precautions in measuring correct vertical jumping height by means of
      force plate measurements.
AB  - The present study was designed to investigate the determination of vertical
      jumping height by means of force plate measurements. Four different sources of
      error influence this determination: the measurement of body mass, the
      determination of take off, the integration frequency, and the assessment of the
      initial conditions influencing the determination of the start of the movement. A
      theoretical model was utilized to simulate the vertical ground reaction forces in
      vertical jumping and to compare the outcome of analytical and numerical double
      integration of the vertical acceleration of the body centre of mass. A high
      integration frequency and an optimizing loop for body mass determination were
      found to be important and should be taken into account when determining jumping
      height parameters.

PMID- 11450879
TI  - Selective immunointervention in autoimmune diseases: lessons from multiple
      sclerosis.
AB  - Activation of peripheral T cells by foreign and self antigens is under stringent
      control by different mechanisms, both thymic and peripheral. Control of T cell
      reactivity is accomplished by three major types of mechanisms: 1) deletion, the
      physical elimination of T cells specific for a given antigen, 2) anergy, the
      functional incapacity of T cells to respond to antigen, 3) suppression, the
      inhibition of T cell function by a regulatory (suppressor) cell. Their failure
      may lead to autoimmune diseases. The progress in understanding T cell activation,
      inactivation and modulation is being translated into strategies able to induce
      selective immunosuppression to treat different pathological situations, notably
      autoimmune diseases, allergies, and allograft rejection. The medical need for
      selective immunosuppression is very high, as the available immunosuppressive
      drugs are substantially inadequate because of limited efficacy, modest
      selectivity, and considerable toxicity. Key attack points for selective
      immunointervention have been identified: modulation of antigen recognition, co
      stimulation blockade, induction of regulatory cells, deviation to non-pathogenic
      or protective responses, neutralization of proinflammatory cytokines, induction
      or administration of anti-inflammatory cytokines, and modulation of leukocyte
      trafficking. All these forms of immunointervention have been successfully used to
      prevent and sometimes treat experimental autoimmune diseases. Based on these
      results, expectations have been raised for exploiting the same strategies to
      inhibit the activation of human autoreactive T cells. In this overview, we will
      examine recent advances towards immunointervention in multiple sclerosis (MS) as
      a paradigm for successes and failures of current immunotherapeutic approaches in
      human autoimmune diseases.

PMID- 11450880
TI  - Current treatment of high grade osteosarcoma of the extremity: review.
AB  - The authors review their lengthy experience in treating high grade osteosarcoma
      of the extremity. During the past 20 years many advances have been made in
      treating high grade osteosarcoma of the extremity. Twenty years ago, in spite of
      amputation, most patients with this tumor died, whereas today most are cured and
      amputation is avoided. These advances are mainly due to the development of
      effective adjuvant and neoadjuvant chemotherapy regimens. This review reports on
      the progress and controversies in the treatment of osteosarcoma.

PMID- 11450881
TI  - In vitro evaluation of BI 397, a novel glycopeptide antimicrobial agent.
AB  - BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL
      62,476 (A40926), has excellent in vitro activity against a wide range of Gram
      positive organisms. In this extensive study, 630 contemporary (1998-2000) Gram
      positive isolates were selected from various resistance surveillance studies for
      their resistance patterns to fluoroquinolones, macrolides-lincosamides
      streptogramins, beta-lactams and glycopeptide agents. The BI 397 spectrum of
      activity was similar to that of other glycopeptides with a MIC90 of < or =0.5
      microg/ml for all tested isolates with the exception of vancomycin-resistant
      enterococci Van A; (MIC90, 32 microg/ml). BI 397 was more potent than vancomycin
      and teicoplanin against Staphylococcus aureus (2- to 8-fold), beta-haemolytic
      streptococci (equal to >16-fold), viridans group streptococci (equal to >32
      fold), and Corynebacterium spp. including C. jeikeium (8- to >16-fold). BI 397
      was also more active than quinupristin/dalfopristin against all Gram-positive
      organisms tested with the exception of oxacillin-susceptible S. aureus, against
      which it had equal activity. BI 397 has little activity against Haemophilus
      influenzae (MIC90, 64 microg/ml) or other Gram-negative bacilli (MIC90, >64
      microg/ml). BI 397 exhibited bacteriostatic activity (like the vancomycin
      control) versus most species, but was bactericidal against tested Streptococcus
      pneumoniae. In vitro testing conditions with blood supplemented or free protein
      containing media elevated BI 397 MIC results, and the 30-microg disk seems
      acceptable for further disk diffusion test development. Animal pharmacokinetic
      data published elsewhere suggest that BI 397 may be dosed less frequently than
      teicoplanin and the results of early studies in humans are awaited with interest,
      especially when treating teicoplanin-refractory coagulase-negative staphylococci.

PMID- 11450882
TI  - Antibacterial activity and post-antibiotic effect of flurithromycin compared with
      other macrolides and penicillins against periodontal pathogens.
AB  - In this study the authors examined the activity of flurithromycin compared to
      that of erythromycin, spiramycin and penicillin against 107 strains of various
      species supposed to cause periodontitis. The range of MICs of flurithromycin was:
      < or =0.06-2 mg/l for P. gingivalis (28 isolates), 0.06-2 mg/l for P.
      melaninogenica (7), 0.5-4 mg/l for P. intermedia (5), 0.25-8 mg/l for Prevotella
      sp. (8), 1-16 mg/l for F. nucleatum (14), 0.12-0.5 mg/l for W. recta (2), 0.5-32
      mg/l for E. corrodens, 0.5-2 mg/l for B. forsythus (2); < or =0.06-64 mg/l for
      Peptostreptococcus sp. (11), < or =0.06-1 mg/l for A. odontolyticus (11) and for
      A. naeslundii (7) and < or =0.06-16 mg/l for A. viscosus (7). Macrolide activity
      was ranked in decreasing order from flurithromycin to erythromycin to spiramycin.
      Beta-lactamase production was demonstrated in Prevotella sp. (20%) and in F.
      nucleatum (7%). Isolates which were beta-lactamase negative but resistant to
      penicillin were found among Peptostreptococcus sp. and Actinomyces sp. A post
      antibiotic effect of 2 hours was seen for flurithromycin on P. gingivalis and E.
      corrodens. The good in vitro activity of flurithromycin against bacteria supposed
      to cause periodontitis suggests clinical potential in the treatment of these
      diseases.

PMID- 11450883
TI  - Antibiotic resistance among Gram-negative non-fermentative bacteria at a teaching
      hospital in Saudi Arabia.
AB  - The incidence and antimicrobial resistance of Gram-negative non-fermentative
      bacteria isolated over 1 year at King Abdulaziz University Hospital, Jeddah,
      Saudi Arabia were investigated. A total of 499 of these microorganisms were
      collected and account for 16% of all Gram-negative bacteria isolated. The most
      common species were Pseudomonas aeruginosa 291 (56%), Acinetobacter baumannii 170
      (34%), and Stenotrophomonas maltophilia 35 (7%). 168 (34%) of these
      microorganisms were isolated from Intensive Care Unit (ICU), 147 (30%) from
      General Medicine, and 24 (25%) from Surgery wards. ICU was the main site of
      isolation of P. aeruginosa and S. maltophilia, while A. baumannii was more
      frequently isolated from medicine and surgery units. The vast majority of the
      isolates were resistant to many antibiotics tested. The antimicrobial resistance
      patterns of P. aeruginosa showed lowest resistance to imipenem (13%), amikacin
      (17%), and ciprofloxacin (18%). Imipenem was also the most active antimicrobial
      agent against A. baumannii (15%) resistance. S. maltophilia exhibited multi-drug
      resistance, and was susceptible only to sulfonamide (6%).

PMID- 11450884
TI  - Systemic and intracerebral infections of mice with Listeria monocytogenes
      successfully treated with linezolid.
AB  - Linezolid is an oxazolidinone derivative which is active mostly against Gram
      positive bacteria. In this work its activity against the facultatively
      intracellular bacterium Listeria monocytogenes was examined in vitro, in tissue
      culture and in animal models of systemic and intracerebral infection and compared
      with ampicillin which is the antibiotic of choice for treatment of listeriosis.
      All strains of L. monocytogenes were susceptible to the substance, with minimal
      inhibitory concentrations (MICs) determined by E-test ranging from 0.38 to 1.5
      mg/l which is below the preliminary breakpoint of this substance. Linezolid was
      bacteriostatic against L. monocytogenes since up to 64 times the MIC did not kill
      the bacteria in 24 hours. Linezolid was also bacteriostatic on L monocytogenes in
      infected tissue culture cells. In animal models of systemic and intracerebral
      infection, linezolid was able to inhibit bacterial growth but was clearly less
      effective than ampicillin. In conclusion, linezolid might be useful for the
      treatment of infections with L monocytogenes in humans when ampicillin may not be
      used.

PMID- 11450885
TI  - Pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) in neonates.
AB  - The pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) was studied in 16
      neonates, divided for analysis into three groups according to gestational age:
      group 1 >36 weeks (n=7); group II between 34-36 weeks (n=4); and group III <34
      weeks (n=5). The serum netilmicin (mean +/- SD) 4h and 24h after the first dose
      were 4.7 +/- 0.8 and 0.8 +/- 0.5 mg/L; 4.9 +/- 0.8 and 1.9 +/-0.2 mg/L; 4.9 +/-
      0.5 and 1.7 +/- 0.5 mg/L in groups I, II and III respectively. After the second
      dose, concentrations at 2, 4, 8, 16 and 24 h were 7.2 +/- 1.0, 5.0 +/- 0.8, 3.0
      +/- 0.6, 1.7 +/- 0.4 and 0.9 +/- 0.2 mg/L (group I); 8.6 +/- 0.2, 6.1 +/- 0.5,
      4.2 +/- 0.7, 2.6 +/- 0.1 and 1.4 +/- 0.4 mg (group II); 9.0 +/- 1.2, 6.3 +/- 0.9,
      4.1 +/- 0.7, 2.6 +/- 0.5 and 1.7 +/- 0.3 mg/L (group III). There was a large
      degree of inter-patient variability in serum concentrations and serum half-life
      (t1/2), volume of distribution (VD), area-under-the-curve (AUC), relative serum
      clearance (Clp) such that these parameters could not be correlated to age or
      weight. Absolute serum clearance (L/h) was correlated with gestational age (r =
      0.672, P <0.01). There was no statistically significant evidence of accumulation
      between the first and second doses for any patient group. One baby from each
      group II and group III had concentration >2 mg/L 24h after the first dose and one
      baby from group III had concentration >2 mg/L 24h after the second dose. There
      are no established correlations between serum netilmicin concentrations and
      efficacy or toxicity in neonates and keeping 24 h trough concentration below 2
      mg/L with a once-a-day dose of 4.5 mg/L would have to be validated in terms of
      its clinical efficacy and potential toxicity in a neonatal population.

PMID- 11450886
TI  - Comparative study of cefixime alone versus intramuscular ceftizoxime followed by
      cefixime in the treatment of urinary tract infections in children.
AB  - Urinary tract infections (UTI) can cause acute morbidity and may result in severe
      problems, including hypertension and reduced renal function. Diagnosis of UTI is
      extremely important since prompt treatment may prevent damage. In the present
      study we compared the efficacy of oral cefixime to initial intramuscular
      ceftizoxime followed by cefixime for the treatment of UTI in children. Fifty-four
      children were studied. They were randomized to receive either oral cefixime 8
      mg/kg/day for 10 days or initial intramuscular ceftizoxime (Cefizox) 50 mg/kg
      twice a day for 2 days followed by oral cefixime for 8 days. Treatment groups
      were comparable regarding age, sex, clinical, and laboratory findings.
      Escherichia coli was isolated from 80% of patients. Repeat urine cultures were
      sterile within 24 hours in all children. Cure rates were comparable in both
      groups (92% vs 86% at the end of treatment). No serious adverse effects were
      observed. We concluded that oral cefixime is a safe and effective alternative
      treatment.

PMID- 11450887
TI  - Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or
      meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.
AB  - Infection remains the major cause of morbidity and mortality in immunocompromised
      children with malignancy. In addition, the economic impact of antibiotic
      treatment should always be evaluated, especially in developing countries. In our
      center between January 1998 and January 1999, 73 children with hematological
      malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)];
      9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile
      neutropenic episodes (related to chemotherapy). These children were randomized
      prospectively into three treatment groups. The first group (n: 28) received
      cefepime plus netilmicin, while the second group (n: 29) was treated with
      ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy.
      The aim of the study was to compare the success rates and cost of fourth
      generation cephalosporin plus aminoglycoside and monotherapy of meropenem with
      ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia.
      Microbiologically documented infections were 29.9%, clinically documented
      infections were 9.2% and 60.9% of the febrile neutropenic episodes were
      considered to be FUO. Gram-positive microorganisms were the most commonly
      isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus
      aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4
      patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and
      3rd groups respectively. In 4 patients (4.5%) fever responded only to
      amphotericin-B therapy. There was no statistically significant difference between
      the three treatment regimens with respect to efficacy, safety and tolerance (chi2
      test, p>0.05), but while the third and fourth generation cephalosporins +
      aminoglycosides were comparable for cost, the monotherapy regimen was the most
      expensive. The main determining factors for the choice of treatment of febrile
      neutropenic children, especially in a developing country, are cost, presence of
      indwelling catheter and the bacterial flora of the unit, as well as efficacy.

PMID- 11450888
TI  - Efficacy of gemifloxacin in acute exacerbations of chronic bronchitis: a
      randomised, double-blind comparison with trovafloxacin.
AB  - This randomised, double-blind, double-dummy, multinational study compared the
      efficacy and safety of gemifloxacin with trovafloxacin in the treatment of acute
      exacerbations of chronic bronchitis. There were 617 patients randomised: 303 to
      gemifloxacin and 314 to trovafloxacin. Clinical success rates at follow-up
      (clinical per-protocol population) were 91.5% for gemifloxacin and 87.6% for
      trovafloxacin. For the intent-to-treat population, the clinical efficacy of
      gemifloxacin was statistically significantly superior to that of trovafloxacin.
      In general, the in vitro activity of gemifloxacin against the major respiratory
      bacterial pathogens was superior to that of other antibiotics tested. Per-patient
      bacteriological success rates at follow-up (bacteriology per-protocol population)
      were 86.8% for gemifloxacin and 82.4% for trovafloxacin. Both agents were well
      tolerated. The clinical and bacteriological efficacy of a once-daily 5-day course
      of gemifloxacin is at least as good as that of a similar regimen of trovafloxacin
      in the treatment of acute exacerbations of chronic bronchitis.

PMID- 11450889
TI  - Effect of perorally administered pivmecillinam on the normal oropharyngeal,
      intestinal and skin microflora.
AB  - To study the ecological effects of pivmecillinam on the human oropharyngeal,
      intestinal and skin microflora, 15 healthy volunteers were given pivmecillinam
      tablets 400 mg twice daily for 7 days. Saliva, stool and skin specimens were
      taken before (days -3 and 0) and on the 2nd, 4th and 7th days during the
      administration period and 14 and 21 days after the start of administration.
      Mecillinam caused no major changes in the aerobic or anaerobic oropharyngeal
      microflora. In the aerobic intestinal microflora there was a decrease in the
      numbers of Escherichia coli while no changes occurred in the anaerobic
      microflora. In the skin microflora there was a transient decrease in the numbers
      of Propionibacterium spp. underneath the wing of the nose. The major effect of
      pivmecillinam was seen on E. coli and to some extent on Propionibacterium spp. No
      further ecological disturbances were noticed in the oropharyngeal, intestinal or
      skin microflora.

PMID- 11450890
TI  - In vitro activity of vinorelbine on human leukemia cells.
AB  - Vinorelbine (VNR) is a semi-synthetic Vinca rosea alkaloid that has been employed
      both as a single agent and in combination, and has shown significant antitumor
      activity. As little is known about VNR activity on human leukemia, we studied its
      in vitro cytotoxic effect on human leukemia cell lines (FLG 29.1, HL60, K562,
      Balm 4, CEM and Daudi) and on fresh leukemia cells from 28 patients: 2 acute
      myeloid leukemia (AML); 3 chronic myeloid leukemia in blastic phase (CML-BP); 5
      acute lymphoblastic leukemia (ALL); 18 B-chronic lymphatic leukemia (B-CLL),
      employing the colorimetric INT assay and determining the IC50. We observed that
      VNR exerts its cytotoxic activity on leukemic cell lines in a dose-dependent
      fashion. The lymphoid cell lines appear more sensitive than the myeloid ones to
      the VNR-dependent growth inhibition. A similar pattern was noticed for leukemia
      cells in primary cultures. VNR is not effective on CML-BP cells, shows variable
      activity on the AML and ALL cells and is very effective against B-CLL cells. VNR
      inhibited the growth of fresh B-CLL cells from 15 of 18 patients, the IC50 doses
      ranging from 4 ng/ml to 83 microg/ml (doses coinciding with the plasma levels
      obtained in clinics). These observations strongly suggest that VNR could be
      useful in clinics for the treatment of B-CLL.

PMID- 11450891
TI  - Correlation between cystatin C and serum creatinine as markers of renal function
      in patients with neoplasms of the locomotor system.
AB  - Creatinine levels and clearance are used to monitor renal function in clinical
      practice. Cystatin C is produced by most nucleated cells in a consistent manner,
      uninfluenced by inflammatory processes, sex, age, eating habits or nutritional
      status. Serum cystatin C concentrations are mainly dependent on glomerular
      activity and are an endogenous biochemical marker of glomerular filtration. The
      aim of this study was to test the efficiency of cystatin C assay as an
      alternative marker of renal function. Statistical analysis of our results showed
      that cystatin C levels were significantly correlated to creatinine and creatinine
      clearance levels. However, it is still premature to suppose that cystatin C can
      replace creatinine in routine tests. Establishing cystatin C levels can be useful
      in cases in which it is not possible to determine creatinine clearance.

PMID- 11450892
TI  - Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma:
      results in eleven cases.
AB  - Between January 1995 and December 1999, 11 patients with synchronous multifocal
      osteosarcoma (SMO) received neoadjuvant treatment with high-dose methotrexate,
      cisplatinum, Adriamycin, and ifosfamide. After primary chemotherapy in 4 patients
      who had only two bone localizations, it was possible to treat all tumor foci
      locally. The remaining patients, with more than three bones involved, were
      treated surgically only in 3 cases at the primary site, while secondary lesions
      did not receive any treatment. The final results of our study were disappointing.
      All patients died of the tumor 6 to 24 months after the beginning of treatment
      (mean 11.9 months). Nevertheless, the survival time of the 4 patients with
      locally treated lesions was significantly longer than the one of 7 patients in
      whom the secondary lesions were not locally treated (18.2 vs 9.1 months;
      P<0.008). It should be noted that those patients simultaneously operated on two
      sites, the response to chemotherapy of "primary" and "secondary" lesions was
      always similar. This homogeneity supports the thesis that in synchronous
      multifocal osteosarcoma the tumors are not multicentric in origin but represent
      bone-to-bone metastases from a monocentric tumor.

PMID- 11450893
TI  - Bacteriophages transducing antibiotic resistance from a cluster of lysogenic
      strains of Pseudomonas aeruginosa isolated from patients.

PMID- 11450894
TI  - Modulation of Akt activity by doxorubicin in breast cancer cells.

PMID- 11450895
TI  - Effect of amifostine on lipid peroxidation caused by cisplatin in rat kidney.

PMID- 11450896
TI  - Nosocomial candidemia in geriatric patients.

PMID- 11450897
TI  - Optic neuropathy and central retinal artery occlusion in non-Hodgkin lymphoma.
AB  - We report a patient with systemic large cell non-Hodgkin lymphoma in remission
      who presented with the rare combination of optic neuropathy and central retinal
      artery occlusion. Another unusual feature of this case is the lack of enhancement
      in the affected region on magnetic resonance imaging only hours after the first
      dose of steroids. Despite prompt treatment with steroids and radiotherapy,
      lymphomatous infiltration of the meninges developed 2 months later and was
      ultimately fatal.

PMID- 11450898
TI  - Postpartum pituitary hypophysitis.
AB  - The case of a young woman who developed lymphocytic hypophysitis 2 weeks after
      delivery of a healthy baby is reported. The patient presented with clinical
      features suggestive of a pituitary mass lesion, but surgery was avoided when
      other clinical and radiologic features were considered. The patient recovered
      with steroid treatment only. We review the literature on this increasingly
      recognized condition and argue that medical management may be more suitable than
      previously thought.

PMID- 11450899
TI  - Interferon-alpha 2a treatment of neuro-Behcet disease.
AB  - Behcet disease is a multisystemic, chronic, recurrent inflammatory disorder
      characterized as a triad of hypopyon uveitis, oral aphthae, and genital ulcers.
      Neurologic involvement in Behcet disease (neuro-Behcet) is common. Neuro-Behcet
      disease typically manifests late after disease onset, rarely coincides with
      ocular involvement, and often heralds a poor prognosis for final vision and
      survival. We present a case of neuro-Behcet disease with neurologic onset
      concomitant with systemic and ocular involvement that was responsive to treatment
      with interferon-alpha 2a.

PMID- 11450900
TI  - Neuro-ophthalmic manifestations of head trauma.
AB  - OBJECTIVE: To describe the neuro-ophthalmic findings in a group of patients with
      head trauma. MATERIALS AND METHODS: A retrospective chart review of all patients
      given a diagnosis code of head trauma in the neuroophthalmology unit at Emory
      University between 1991 and 1999. RESULTS: A total of 326 consecutive patients
      were reviewed (203 [63%] men and 123 [37.0%] women). Age ranged from 2 to 86
      years, with a mean of 30 years. Motor vehicle accident was the most common cause
      of head trauma, occurring in 195 (59.8%) patients. An abnormal neuro-ophthalmic
      examination was noted in 185 of 326 patients (56.7%). Loss of consciousness was
      not associated with any outcome, but the presence of a neuroimaging abnormality,
      particularly intracranial hemorrhage, was significantly associated with specific
      neuroophthalmic deficits. CONCLUSIONS: Head trauma causes a number of
      neuroophthalmic manifestations. The afferent and efferent pathways are vulnerable
      to traumatic injury, although the efferent system is more commonly affected. Loss
      of consciousness may not be a reliable predictor of specific neuro-ophthalmic
      outcomes, but neuroimaging abnormalities may.

PMID- 11450901
TI  - When does low mean high? Isolated cerebral ventricular increased intracranial
      pressure in a patient with a Chiari I malformation.
AB  - OBJECTIVE: To present an unusual case of pseudotumor cerebri with increased
      intracranial pressure isolated to the cerebral ventricles resulting from a Chiari
      I malformation. MATERIALS AND METHODS: The patient received a complete
      ophthalmologic examination on initial presentation and subsequent visits,
      including visual acuity, pupillary examination, intraocular pressures, dilated
      fundus examination with assessment of degree of papilledema, and visual field
      testing. Intracranial pressure was measured by lumbar puncture and subsequently
      by intracranial pressure bolt monitoring. Magnetic resonance imaging (MRI) was
      used to diagnose the Chiari I malformation. RESULTS: The patient initially
      presented with bitemporal headaches, elevated opening pressure on lumbar
      puncture, and mild papilledema with a normal MRI. After lumboperitoneal shunt
      placement and several revisions, the patient presented with decreased vision OD
      secondary to Terson syndrome and worsening papilledema. Subsequent evaluation
      revealed normal lumbar opening pressures and a Chiari I malformation. She
      underwent ventriculoperitoneal shunt placement with resolution of her symptoms.
      CONCLUSIONS: Tonsillar herniation is a well-documented complication of
      lumboperitoneal shunt revision. Obstruction of cerebrospinal flow through the
      foramina of Magendie and Luschka can result in increased intracranial pressure
      isolated to the cerebral ventricles. In a patient with signs and symptoms of
      increased intracranial pressure but normal lumbar opening pressure, a Chiari I
      malformation should be suspected, particularly with a history of multiple
      lumboperitoneal shunt revisions.

PMID- 11450902
TI  - Sleep disorders: a risk factor for pseudotumor cerebri?
AB  - OBJECTIVE: To determine whether sleep-related breathing disorders are common in
      patients with idiopathic intracranial hypertension. MATERIALS AND METHODS:
      Medical records of 53 patients with idiopathic intracranial hypertension from a
      tertiary center neuroophthalmology practice were reviewed. Thirty-seven patients
      were identified who had a history of snoring, difficulty sleeping, or daytime
      somnolence. The data from polysomnograms were tabulated to determine the
      frequency of apneas, hypopneas, and arousals. RESULTS: Fourteen of 37 patients
      with idiopathic intracranial hypertension and symptoms of sleep disturbance
      underwent polysomnography. There were two men and 12 women varying in age from 24
      to 58 years (mean, 39.4 +/- 11.9). These patients were obese with body mass
      indexes varying from 33.0 to 63.2 (mean, 46.0 +/- 9.5). A diagnosis of sleep
      apnea was made in six and upper airway resistance syndrome in seven patients.
      CONCLUSIONS: Sleep-related breathing problems were common in our patients with
      idiopathic intracranial hypertension. Obesity was common in these patients and
      may be playing a causative role in sleep apnea and idiopathic intracranial
      hypertension. It is suggested that idiopathic intracranial hypertension patients
      who have symptoms of sleep disturbance should be further evaluated for the
      presence of sleep-related breathing problems.

PMID- 11450903
TI  - The SKILL Card test in optic neuritis: experience of the Optic Neuritis Treatment
      Trial. Smith-Kettlewell Institute Low Luminance. Optic Neuritis Study Group.
AB  - OBJECTIVES: To assess the value of the Smith-Kettlewell Institute Low Luminance
      (SKILL) Card test, designed to measure vision at reduced contrast and luminance,
      among patients with previous optic neuritis. MATERIALS AND METHODS: The SKILL
      Card test was administered to 295 patients participating in the Optic Neuritis
      Treatment Trial (ONTT) follow-up study, concurrent with measurement of visual
      acuity, visual field, contrast sensitivity, and color vision. Health-related
      quality of life (HRQL) was also assessed in a subset of patients using the
      National Eye Institute Visual Function Questionnaire and an ONTT-developed
      questionnaire. RESULTS: The SKILL Card difference score (high-contrast acuity
      score minus low-contrast acuity score) was only weakly associated with the other
      measures of vision function (rs absolute range, 0.05-0.31) and with the HRQL
      measures (rs absolute range, 0.02-0.15). In contrast, the light and dark
      component scores of the SKILL Card test had higher associations with the other
      vision measures (rs absolute range, 0.27-0.54) and with the HRQL measures (rs
      absolute range, 0.10-0.40). CONCLUSIONS: The SKILL Card difference score is not a
      meaningful measure for patients with optic neuritis; however, the test appears to
      have clinical usefulness as a method to measure high-contrast and low-contrast
      acuity.

PMID- 11450904
TI  - Neuro-ophthalmic manifestations of sarcoidosis: clinical spectrum, evaluation,
      and management.
AB  - OBJECTIVE: To familiarize the reader with the neuro-ophthalmic manifestations of
      sarcoidosis. MATERIALS AND METHODS: All patients underwent systemic evaluations
      (chest radiograph, magnetic resonance imaging and/or computed tomography, serum
      angiotensin-converting enzyme level, and gallium scan). Histologic confirmation
      was preferred (11 of 15 patients underwent biopsy, ten of whom [82%] had positive
      biopsies, and four refused). Otherwise, the diagnosis of clinical sarcoidosis was
      based on laboratory evaluation. RESULTS: We report our experience with 15
      patients who had neuro-ophthalmic manifestations of sarcoidosis other than optic
      neuropathy or chiasmal disease. Eight of 15 (53%) did not have known sarcoidosis
      at the time of presentation. Thirteen of 15 (87%) patients demonstrated lesions
      consistent with sarcoidosis on magnetic resonance imaging of the brain. Treatment
      with corticosteroids and/or other immunomodulatory agents was necessary in all
      cases. CONCLUSIONS: Neuro-ophthalmic manifestations of sarcoidosis are rare. They
      may be the presenting signs of otherwise occult disease. Suspicion and inclusion
      in the differential are a key to establishing the diagnosis. A strategy for the
      detection and evaluation of these cases is presented.

PMID- 11450905
TI  - Systemic disease and neuro-ophthalmology: annual update 2000 (Part II).

PMID- 11450906
TI  - Oculopalatal tremor with tardive ataxia.
AB  - Oculopalatal tremor consists of palatal tremor and pendular nystagmus and may
      develop in a delayed fashion after an acute brainstem lesion. Delayed sequelae
      are generally restricted to the eyes and branchial-derived muscles, such as those
      of the palate. We report three cases of oculopalatal tremor that subsequently
      developed disabling delayed-onset ataxia and emphasize the potential for this
      significant complication after larger bilateral acute brainstem lesions with
      sparing of the inferior olive.

PMID- 11450907
TI  - The effect of lid elevation on the cross-cover test.
AB  - OBJECTIVE: To discern the effect of manual lid elevation on muscle balance using
      the cross-cover test. MATERIALS AND METHODS: One hundred consecutive patients who
      were orthophoric in all fields of gaze were prospectively studied. A repeat cross
      cover test was performed with the eyes looking down and to either side while
      pulling the lid ipsilateral to the abducting eye up and to either side. The
      presence and type of any phoria was noted. RESULTS: Eighty-four percent of
      patients and 76% of eyes developed a phoria with lifting a lid. Vertical phorias
      developed in 79 patients and 136 eyes, whereas horizontal phorias were seen in 51
      patients and 83 eyes. In all but one case, the vertical deviation was a
      hyperphoria ipsilateral to the elevated lid. Horizontal deviations were esophoric
      in 63 eyes of 39 subjects. Induced phorias were most commonly symmetric from side
      to side. CONCLUSIONS: Lifting the lid produces an iatrogenic phoria that mimics a
      skew or IV nerve paresis. We hypothesize that stretching the lid causes traction
      on the levator-superior rectus complex, thereby increasing its tone. Although it
      makes testing more difficult, we recommend that the lids not be manipulated while
      performing phoria testing.

PMID- 11450908
TI  - Olfactory neuroblastoma--an unusual presentation.

PMID- 11450909
TI  - Optic neuropathy in a patient with AIDS.
AB  - We present a patient with acquired immunodeficiency syndrome (AIDS) with
      bilateral sequential optic neuropathies attributed to the 14484 mutation of Leber
      hereditary optic neuropathy (LHON). We discuss the potential interaction of the
      mitochondrial mutation with antiretroviral therapy and review the literature.

PMID- 11450910
TI  - Primary central nervous system lymphoma involving the optic chiasm in AIDS.
AB  - OBJECTIVE: To report visual loss resulting from chiasmal involvement by primary
      central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: Case report.
      RESULTS: A patient with the acquired immune deficiency syndrome (AIDS) presented
      with visual loss resulting from PCNSL involving the optic chiasm. The clinical
      findings, neuroimaging, pathology, and treatment of this patient are described.
      CONCLUSIONS: Although rare, clinicians should consider PCNSL in the differential
      of a hypothalamic/chiasmal mass, especially in a patient with AIDS.

PMID- 11450911
TI  - The Heidenhain variant of Creutzfeldt-Jakob disease: clinical, pathologic, and
      neuroimaging findings.
AB  - We report two patients who developed isolated visual symptoms and signs as
      initial manifestations of Creutzfeldt-Jakob disease (CJD). Both patients had
      normal conventional T1- and T2-weighted brain magnetic resonance (MR) images; in
      one patient, early cortical abnormalities were detected by diffusion-weighted and
      fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI).
      Results from the cerebrospinal fluid assay for the 14-3-3 brain protein were also
      negative in one patient, despite pathologic confirmation of CJD at autopsy. The
      Heidenhain variant of CJD should be considered in all patients who present with
      isolated visual manifestations, including homonymous hemianopsia and normal
      conventional brain MRI. Diffusion-weighted and FLAIR MRI may demonstrate early
      cortical abnormalities in patients with CJD. The CSF assay for the 14-3-3 protein
      may be normal, even in pathologically confirmed cases.

PMID- 11450912
TI  - Mirizzi syndrome: an extra hazard for laparoscopic surgery.
AB  - BACKGROUND: Mirizzi Syndrome (MS) is an important but uncommon complication of
      gallstones characterized by narrowing of the common hepatic duct (CHD) due to
      mechanical compression or inflammation. This study aimed to assess the impact of
      preoperative and intraoperative diagnosis of MS on the performance, safety and
      efficacy of laparoscopic cholecystectomy. METHODS: From a consecutive series of
      1,281 patients having surgery for gall bladder disease between 1990 and 1998,
      nine patients with MS were identified from a prospective database and their
      clinical progress examined. RESULTS: Five out of the nine patients with MS
      presented with pain (2/5 were also jaundiced), and four presented with acute
      cholecystitis. Liver function tests were abnormal in all patients. Preoperative
      diagnosis of MS based on ultrasound was made in only two patients, and in a third
      on findings of a nasobiliary cholangiogram. In six patients, the diagnosis was
      intraoperative. In seven patients cholecystectomy was completed by laparoscopy.
      Two patients needed conversion to open cholecystectomy. In two patients the
      common bile duct was mistaken for the cystic duct and the error was recognized on
      relaxation of traction on the gall bladder in one, but in the other a duct injury
      occurred that was not recognized until the postoperative period. CONCLUSIONS:
      Preoperative diagnosis of MS is difficult, and a high index of suspicion is
      necessary to avoid serious complications. Once the diagnosis is known, successful
      laparoscopic management is possible but care should be taken to avoid duct
      injury.

PMID- 11450913
TI  - Screen-detected breast cancer compared to symptomatic presentation: an analysis
      of surgical treatment and end-points of effective mammographic screening.
AB  - BACKGROUND: Mammographic screening has been shown to reduce mortality from breast
      cancer and to offer more opportunity for breast conservation surgery (BCS). The
      minimum standards (or surrogate end-points) that need to be achieved by a
      screening programme if it is to reduce mortality have been derived from the Two
      County Study. Three surrogate end-points that can be used to gauge the quality of
      the screening service are that 50% of the identified infiltrating cancers should
      be < 15 mm; at least 30% of grade 3 cancers should be < 15 mm; and 70% of screen
      detected cancers should have a negative axillary dissection. The present study
      assesses these end-points of effective screening in an urban population referred
      to The Strathfield Breast Centre (TSBC). The screening end-points and surgical
      treatment of one group of women referred with a BreastScreen New South Wales
      (NSW)-detected breast cancer (screen group) were compared to all the other,
      mostly symptomatic, breast cancer referrals (symptom group). The problems with
      the current pattern of acceptance of mammographic screening in TSBC's referral
      area are discussed. METHODS: A prospective non-randomized study was done via
      analysis of the prospective database at The Strathfield Breast Centre (TSBC).
      RESULTS: There were 224 women in the screen group and 657 women in the symptom
      group. The mean tumour size was 18.1 mm in the screen group and 22.1 mm in the
      symptom group. There were significantly more small invasive cancers (< 15 mm) in
      the screen group (58%) compared with the symptom group (33%; P < 0.001). In the
      screen group there were more low-grade tumours but 30% of grade 3 tumours were <
      15 mm compared with 16% in the symptom group (P = 0.009). In patients with
      invasive cancers who underwent axillary dissection, there was a significant
      difference in axillary node negativity, being 72% in the screen group and 59% in
      the symptom group (P = 0.003). In the screen group 64% of women had BCS compared
      with 51% in the symptom group (P = 0.002). CONCLUSIONS: These end-points of
      effective mammographic screening were met in the BreastScreen NSW group of women
      who were referred to TSBC despite the biases involved which could lessen the
      effectiveness of the screening programme. This crudely translated into a
      significant reduction in breast cancer mortality but selection and lead time bias
      has to be taken into account in evaluation of these data. There was a
      significantly greater chance of BCS in the screen group.

PMID- 11450914
TI  - EVT endovascular graft for abdominal aortic aneurysm.
AB  - BACKGROUND: A variety of prostheses are now available for the endovascular
      treatment of abdominal aortic aneurysm (AAA). Significant advantages of the EVT
      device are its unibody design, secure hook attachment system and graft fabric
      approximating that used in conventional surgery. METHODS: Implantation of the EVT
      device was attempted in 60 patients who were studied prospectively with an
      analysis of subsequent problems encountered. RESULTS: Conversion to open repair
      was required in four cases (6.7%). There were nine tube grafts inserted, 13 aorto
      unilateral iliac with crossover grafts and 34 aorto-bi-iliac grafts. There was
      one death (mortality 1.7%). Endoleaks were identified in eight patients (14%),
      none of which were proximal; three sealed spontaneously, two were treated with
      coil embolization, two are being observed and one patient had an iliac attachment
      converted to an open anastomosis. Access vessel problems were seen in 21 patients
      (35%); two-thirds were corrected at the time of initial surgery. Seven patients
      (12%) had primary graft limb problems identified and treated before leaving the
      operating room. Nine patients (16%) developed secondary graft limb problems,
      which were diagnosed and treated after the initial surgery. Endovascular
      treatment was used in eight and was successful in six with surgical revision
      required in two. On review of these cases to assess if the problem could have
      been predicted at the time of initial surgery, it was felt that more aggressive
      treatment of intraoperatively diagnosed graft limb stenoses, even though
      considered mild, may have prevented 50% of subsequent secondary graft limb
      occlusions. CONCLUSION: Although the EVT device has significant advantages in the
      endovascular management of aortic aneurysm, potential graft limb problems need to
      be actively identified with the majority able to be successfully managed by
      supplementary endovascular techniques.

PMID- 11450915
TI  - Outcome of the acute abdomen in patients with previous spinal cord injury.
AB  - BACKGROUND: Patients with spinal cord injury (SCI) have always posed difficulties
      for the diagnosis of an acute abdomen. The aim of the present study was to define
      this problem retrospectively at Princess Alexandra Hospital and to assess the
      results of treatment for these patients. METHODS: A retrospective review was
      conducted of 133 SCI patients admitted with an acute abdomen in the 16 years
      prior to this analysis at the Spinal Injuries Unit (SIU) of Princess Alexandra
      Hospital. There were 21 patients who conformed to the study criteria. All the
      patients had sustained traumatic SCI at or above the level of T11, more than 1
      month prior to admission. RESULTS: There were 13 male and eight female patients.
      The time lapse between SCI and the onset of an acute abdomen ranged from 1.5
      months to 27 years. The age range was 26-79 years. The majority of patients had
      C6 injuries (six patients). There were 18 patients with injury levels above T6
      and three patients with injuries below this level. The time taken to diagnose the
      cause of the acute abdomen ranged between I day and 3 months. Investigations were
      found to be useful in making the diagnoses in 61.9% of cases. There were 14
      patients who had surgical interventions. Five patients had surgical complications
      and there were two deaths in the study. The length of follow up was 1-132 months.
      The mortality in the study was 9.5%. CONCLUSION: An aggressive approach to the
      diagnosis and treatment of the acute abdomen in SCI patients with suspicious
      symptoms is recommended. A high index of suspicion should be maintained in those
      patients with pre-existing SCI who present with abdominal trauma.

PMID- 11450916
TI  - Active observation of children with possible appendicitis does not increase
      morbidity.
AB  - BACKGROUND: Attempts to maximise diagnostic accuracy and reduce unnecessary
      surgery have led to the hospital observation of children with suspected
      appendicitis but unconvincing physical signs. However, morbidity associated with
      perforation necessitates the prompt management of acute appendicitis and
      increases anxiety concerning prolonged preoperative observation. METHODS: To
      assess the preoperative delay and subsequent complications associated with active
      observation of appendicitis, we reviewed the records of 378 children who had an
      appendicectomy performed at the Women's and Children's Hospital during a 4-year
      period. RESULTS: Active observation was associated with an overall diagnostic
      accuracy of 93%. The mean preoperative hospital time was 12 h. The incidence of
      gangrene or perforation was 32%, with a mean preoperative hospital time in this
      group of 7 h. In view of the short preoperative waiting time in this group, we do
      not believe perforation in hospital to have been a frequent occurrence. The
      overall incidence of postoperative infective complications was 4%, with an
      incidence of 12% following perforation. CONCLUSIONS: Children with advanced
      disease often have convincing signs on presentation and are not usually subjected
      to a significant delay. Active observation is not associated with high
      postoperative morbidity.

PMID- 11450917
TI  - 1alpha,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093, profoundly
      inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2.
AB  - BACKGROUND: 1alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been shown to inhibit
      the proliferation of various cancer cells including colon, prostate, melanoma,
      osteosarcoma and breast cancer. METHODS: The human hepatoma cell line (HepG2) was
      cultured with 1,25(OH)2D3 or one of two analogues EB1089 or CB1093 for various
      durations. Cellular proliferation was measured by uptake of [3H]thymidine, and
      cell numbers were determined by trypan blue exclusion counting. RESULTS:
      1,25(OH)2D3, EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90%
      after 5 days of treatment, compared to the untreated controls. Decreased
      proliferation was associated with an approximately 50% reduction in cell numbers
      at concentrations of up to 10(-10) mol/L after 5 days of treatment with
      1,25(OH)2D3. Cell proliferation rapidly recovered in cultures treated with lower
      concentrations of 1,25(OH)2D3 (10(-10) and 10(-11) mol/L) when 1,25(OH)2D3 was
      removed from the cultures by placing cells in serum containing medium without
      1,25(OH)2D3. When HepG2 cells were treated with 10(-8) mol/L 1,25(OH)2D3 for 5
      weeks, there was still significant inhibition of proliferation, although at week
      5 there was 66% inhibition compared to 93% at the end of week 1. CONCLUSIONS:
      1,25(OH)2D3, EB1089 and CB1093 all significantly inhibit the proliferation of
      HepG2 hepatoblastoma cells, with EB1089 being the most potent at lower
      concentrations. Inhibition can be maintained for at least 4 weeks, but is
      reversed after removal of vitamin D3.

PMID- 11450918
TI  - Preliminary study of the anatomy of the venous drainage of the intrahepatic and
      extrahepatic bile ducts and its relevance to the practice of hepatobiliary
      surgery.
AB  - BACKGROUND: Although there have been many studies of the arterial supply of the
      biliary system, attempts to study the corresponding venous drainage have been few
      and all have been incomplete. The purpose of the present investigation is to
      describe the anatomy of the venous drainage of both the intrahepatic and
      extrahepatic bile ducts and to determine its relevance to hepatobiliary surgery.
      METHODS: The intrahepatic and extrahepatic venous drainage of the bile ducts was
      investigated in seven specimens by injecting a solution of 10% gelatin coloured
      with Alcian blue into the portal vein or the superior mesenteric vein to outline
      the venous drainage. The specimens were dissected under loop magnification and
      representative drawings were obtained. RESULTS: The surface of the intrahepatic
      and extrahepatic bile ducts was covered by a fine venous plexus. On the surface
      of the supraduodenal common hepatic duct and common bile duct the venous plexus
      drained laterally into marginal veins, usually two in number and known as the 3
      o'clock and 9 o'clock marginal veins. Inferiorly the marginal veins and the
      venous plexus communicated with the pancreaticoduodenal venous plexus, which in
      its turn drained into the posterosuperior pancreaticoduodenal vein, a branch of
      the superior mesenteric vein. Superiorly the marginal veins divided into a number
      of branches. Some branches followed the left and right hepatic ducts into the
      liver, communicating with the venous plexus and the adjacent branches of the
      portal vein. Other branches of variable size entered either segment IV or the
      caudate lobe or process via the hilar venous plexus. A most important finding was
      that even after dividing the bile duct and all communicating veins at the upper
      border of the duodenum, the venous plexus and the marginal veins filled normally
      to the level of transection. This occurred almost certainly by retrograde filling
      from above. CONCLUSION: The satisfactory results of end-to-end anastomosis in
      whole liver transplantation depends partly on the presence of adequate venous
      drainage. This has been amply demonstrated by the injection studies. This would
      indicate that the poor results of end-to-end repair of the bile duct after
      surgical trauma results from other factors such as poor technique,
      devascularization of the cut ends due to trauma, and carrying out the anastomosis
      under tension. After resection of the hilum for cholangiocarcinoma the venous
      drainage of the left and right hepatic ducts and their branches depends mainly on
      the communications between the venous plexus on the ducts and the adjacent
      branches of the portal vein, even at a lobular or sinusoidal level. The
      satisfactory results obtained after anastomosis of the left and right hepatic
      ducts or their branches to a Roux loop ofjejunum attest to this. This applies
      also to the transplantation of segments II and III in paediatric patients from
      related adult donors and in patients receiving split liver transplants. Finally,
      the venous drainage at the bifurcation of the common hepatic duct has been shown
      to enter the caudate lobe and segment IV directly. This suggests that a hilar
      cholangiocarcinoma may metastasize to these segments, and perhaps partly explain
      the significantly better long-term results when the caudate lobe and segment IV
      are resected en bloc with the cholangiocarcinoma as part of modern radical
      surgery for this condition.

PMID- 11450919
TI  - Management of Mirizzi syndrome: a new surgical approach.
AB  - BACKGROUND: In a prospective study of a patient population of 1,340 with biliary
      calculus disease, that ran from January 1993 to December 1997, 34 patients
      (2.53%) were identified as having Mirizzi syndrome. Eight patients were found to
      have type I (A and B) and 26 patients were found to have type II Mirizzi
      syndrome. A history of recurrent biliary colic and jaundice was present in the
      majority of patients. METHODS: Ultrasonography was helpful in five patients and
      endoscopic retrograde cholangiopancreatography was helpful in 17 patients in the
      diagnosis of this condition. Because the amount of gall bladder tissue used in
      choledochoplasty is not yet standardized, a new policy regarding choledochoplasty
      was adopted. In type IA, retrograde cholecystectomy with simple closure of cystic
      duct was carried out. In type IB, retrograde cholecystectomy and choledochoplasty
      with 5 mm cuff of the gall bladder was carried out. In type II lesions the
      procedure depended on the size of fistula. Patients with fistula sizes of less
      than one-third of the common bile duct diameter underwent choledochoplasty with 5
      mm cuff of the gall bladder, and patients with fistula sizes between one-third
      and two-thirds of the diameter of the common bile duct underwent choledochoplasty
      with 10 mm cuff of the gall bladder. Patients with fistula sizes of more than two
      thirds of the common bile duct diameter underwent Roux-en-Y hepaticojejunostomy.
      RESULTS: There was no operative mortality and the complication rate was 17.64%.
      CONCLUSION: Although, out of 26 choledochoplasties, we encountered only one
      (3.84%) stump stone in a maximum follow-up period of 59 months, further long-term
      follow-up studies are required to prove the efficacy of the procedure.

PMID- 11450920
TI  - Adenocarcinoma of the small bowel.
AB  - Cancer of the small bowel is a rare entity but its incidence is rising.
      Historically, outcome is poor despite apparent curative resection. At present
      surgery remains the only treatment modality of proven benefit in the management
      of this disease. Recent data would suggest 5-year survival rates in the order of
      40-50% at all sites of small bowel cancer. To improve upon this, earlier
      diagnosis with a high index of suspicion and multicentre adjuvant therapy trials
      are required.

PMID- 11450921
TI  - Positive sentinel node biopsy in male breast carcinoma.

PMID- 11450922
TI  - Intracystic papillary carcinoma of the breast.

PMID- 11450923
TI  - Laryngopyocoele: an unusual cause of airway obstruction.

PMID- 11450924
TI  - Laparoscopic repair of Bochdalek hernia in an adult.

PMID- 11450925
TI  - Identifying 'non-medical' datasets to monitor community health and well-being.
AB  - BACKGROUND: The aim of the study was to identify 'non-medical' datasets holding
      routinely collected information that might be used to measure and monitor the
      wider determinants of community health and well-being. METHODS: An expert panel
      discussion, involving public health and environmental health academics and
      professionals with expertise in a variety of backgrounds (including environmental
      health, housing, transport, community safety, public health, primary and
      secondary care), and interrogation of the Office for National Statistics database
      were carried out for the West Midlands region. The aim was to identify routinely
      collected 'non-medical' datasets containing information on the following factors:
      physical environment, crime, housing and homelessness, social services, socio
      economic environment including employment, lifestyles, education, leisure and
      culture, transport and accidents. RESULTS: Fifty-six datasets were identified.
      Although 43 (77 per cent) were collected at least annually, few (17; 30 per cent)
      held data that were disaggregated and routinely available at the sub-local
      authority level. CONCLUSIONS: This study has identified a number of datasets that
      hold information relevant to health. However, no single dataset is likely to
      provide information on all dimensions of health and the determinants of health,
      and local agencies should consider carefully the strengths and weaknesses of
      each. Through the development of inter-sectoral working and multi-agency
      involvement at the local level there is now considerable scope to improve the
      quality of many of these datasets and to promote their use in the measurement and
      monitoring of community health.

PMID- 11450926
TI  - Is untargeted outreach visiting in primary care effective? A pragmatic randomized
      controlled trial.
AB  - BACKGROUND: There is increasing evidence that clinical guidelines can lead to
      improvements in clinical care. However, they are not self-implementing. Outreach
      visits may improve prescribing behaviour. METHODS: Within a before-and-after
      pragmatic randomized controlled trial, involving all general practices in one
      health district, routine methods were used to distribute guidelines for
      management of Helicobacter pylori eradication. Intervention practices were
      offered a visit and the conduct of an audit by a pharmacist trained in the
      techniques of outreach visiting. The intervention was evaluated using level three
      Prescribing Analysis and Cost (PACT) data for metronidazole and omeprazole for
      the two 12 month periods around the introduction of the guidelines. RESULTS: Of
      the 38 intervention practices 19 accepted an outreach visit and three accepted
      the offer of an audit. There was a significant increase in omeprazole use during
      the study of 0.24 [95 per cent confidence interval (CI) +0.19 to +0.29] dose
      units per year but no effect from the offer [-0.02 (95 per cent CI -0.12 to
      +0.08) dose units] or acceptance of a visit [-0.03 (95 per cent CI -0.15 to
      +0.08) dose units]. The results for metronidazole were similar, with an increase
      in use of 0.028 (95 per cent CI +0.018 to +0.038) dose units per year. The effect
      of the intervention was a non-significant change in prescribing of -0.005 (95 per
      cent CI -0.025 to +0.015) dose units. Accepting a visit had little effect on
      prescribing: a change of 0.003 (95 per cent CI -0.021 to +0.027) dose units.
      CONCLUSIONS: The routine use of untargeted outreach visiting is probably not a
      worthwhile strategy.

PMID- 11450927
TI  - The role of community pharmacists in prescribing medication for the treatment of
      head lice.
AB  - BACKGROUND: The aim of the study was to discover whether the use of community
      pharmacy, rather than general practice, as the first port of call for suspected
      head lice infestation would represent an acceptable, effective and cost-reducing
      means of management in the community. METHODS: A before-and-after study was
      carried out of a new system of care delivery. Between September and November
      1997, pharmacists in Nottingham City West recorded details of all patients
      attending with prescriptions for head lice treatment or those purchasing over-the
      counter medication. The new system of care delivery began in January 1998, during
      which, pharmacists were providing advice and treatment for head lice, in the
      absence of a referral from general practice. Changes in prescribing behaviour
      were assessed from Prescribing Analysis and Cost (PACT) data. Acceptability and
      subjective assessment of the scheme (patients and professionals) was gauged from
      questionnaires. RESULTS: Referral patterns were altered drastically (away from
      general practice and towards self-referral) by the project, and the changes were
      apparent within the first month. This trend continued throughout and beyond the
      formal evaluation period. Cost analysis suggests that the community pharmacy
      scheme generates resource savings, largely driven by the lower cost of a pharmacy
      consultation, as opposed to a GP consultation. Questionnaire evidence suggests
      that both patients and health care professionals viewed the new arrangement as at
      least as acceptable as the old. CONCLUSION: With respect to the original
      objective, the new delivery system appears to provide no evidence of
      ineffectiveness; evidence of acceptability on the part of the majority of
      patients and professionals; and evidence of improved cost-effectiveness.

PMID- 11450928
TI  - An assessment of need for health visiting in general practice populations.
AB  - BACKGROUND: An index of the need for health visiting in general practice
      populations in the United Kingdom was developed, using routinely held data, to
      inform decisions about the deployment of health visitors. METHODS: The following
      indicators of need for health visiting were developed by consensus among health
      visitors and others: the population aged under 5 years; elective admissions under
      5 years; births under 2,500 g; deaths under 65 years; all expressed as rates per
      10,000 people registered with general practices in Norfolk. All indicators were
      compared with the number of health visitors per 10,000 people, obtained by a
      postal survey of health visitors. The indicators were converted to Z-scores and
      summed to produce a composite score of need for each general practice. The
      results were compared with the results of a workload profile using data compiled
      by health visitors within one Primary Care Group. RESULTS: Health visitors are
      not allocated according to need at either the practice or Primary Care Group
      level. The Pearson's correlation coefficient between the allocation suggested by
      this method and current allocation is 0.37 (p < 0.01). The correlation between
      this method and the allocation suggested by health visitors' workload profiling
      in one Primary Care Group was 0.76 (p < 0.01). CONCLUSIONS: Health visitors are
      currently distributed according to historic patterns rather than need. This paper
      describes a simple method of determining need at general practice level, which
      can be used to allocate health visitors equitably.

PMID- 11450929
TI  - Health status of Gypsy Travellers.
AB  - BACKGROUND: Although previous studies suggest that Gypsy Travellers have poorer
      health status and excess mortality compared with the general population, there is
      no epidemiological evidence using validated measures in this nomadic ethnic
      group. The aim of this study was to compare the health status of traditional
      Gypsy Travellers with norms from the UK population, and with a concurrent
      comparison group using the Euroqol health status measure (EQ-5D). METHODS: Eighty
      seven adult Gypsy Travellers were matched for age and sex with English or Irish
      residents, registered with an urban general practice in an area of high social
      deprivation. Both samples completed the EQ-5D questionnaire by interview. A
      comparison was also made with normative data from the UK general population.
      RESULTS: Travellers had poorer health status than their settled counterparts on
      two of the five dimensions (mobility and activity) but not on the overall summary
      score. Travellers reported significantly poorer health than the matched
      comparison group on the EQ-5D visual analogue scale. Both the Travellers and the
      comparison group had much poorer health status on the EQ-5D index than the UK
      population norms, even when compared with the lowest socioeconomic group.
      CONCLUSIONS: Health status of Gypsy Travellers was significantly poorer than in
      the lowest socio-economic UK population group, but was not so markedly different
      from a concurrent, matched, socially deprived resident group. Gypsy Travellers
      did have poorer health status than matched comparators in relation to mobility,
      activity and perception of overall health. Quantitative assessment of health
      status in the Traveller community is feasible.

PMID- 11450930
TI  - Public health physicians' knowledge of core skills and current policy: clinical
      audit by questionnaire.
AB  - BACKGROUND: The aim of this study was to facilitate the assessment of the
      knowledge of general public health physicians on a range of topics relating to
      everyday areas of work and core skills, and to encourage learning in the process,
      by means of an educational clinical audit exercise. METHODS: A group of experts
      in different aspects of public health were asked to contribute multiple-choice
      questions. These were developed into a questionnaire that could be marked by
      computer. The questionnaire was circulated to all members of the Faculty
      registered for Continuing Professional Development (CPD) and to specialist
      registrar members, but participation was voluntary. The experts marked answers
      according to a marking scheme against model answers agreed. RESULTS: A total of
      499 public health doctors returned answer sheets. There was no 'pass mark' as
      this was a learning exercise, not an examination. However, although the negative
      marking system meant that the possible range of scores was -100 per cent to 100
      per cent, no one had a negative score. The median uncorrected result was 44 out
      of 80. Questions on communicable disease and critical appraisal had the highest
      scores, and one on Primary Care Trusts the lowest. Participants thought the most
      interesting questions were those on epidemiology and evidence-based medicine,
      whereas the most unpopular was on Personal Medical Services pilots. Most comments
      were favourable to the approach but several commented that the whole exercise was
      too general and questions outside their current area of specialization were
      irrelevant. CONCLUSION: The general public health physicians who took part in
      this audit appeared to be mainly competent in their knowledge of core skills and
      up to date with current health policy issues. However, the audit raises a debate
      about what 'core' knowledge is required in the post-training period. The place of
      UK-wide CPD initiatives over national or regional, or local approaches needs
      consideration, as do potential regional or national variations in CPD. This will
      receive further impetus because of revalidation and the need to demonstrate valid
      CPD activities in public health medicine.

PMID- 11450931
TI  - Estimating a population's needs for the treatment of lower urinary tract symptoms
      in men: what is the extent of unmet need?
AB  - BACKGROUND: Prevalence surveys have shown that men aged over 40 commonly
      experience lower urinary tract symptoms (LUTS). However, such studies cannot be
      used in isolation to inform health service planning, as not all men are troubled
      by their symptoms nor would they necessarily benefit from treatment. METHODS: A
      total of 3,540 randomly selected men in Somerset were sent a postal questionnaire
      containing the American Urological Association (AUA) symptom index. Men reporting
      moderate or severe symptoms were invited for clinical assessment to determine
      whether they could benefit from treatment in primary or secondary care. The
      impact of their symptoms on their quality of life was measured using the ICS-QOL
      questionnaire. RESULTS: The prevalence of reported LUTS was 256 per 1,000 men
      aged 40 and over. Of men reporting moderate or severe urinary symptoms, 40 per
      cent considered that they did not interfere with their life at all. The results
      were used to estimate the number of men with moderate or severe urinary symptoms,
      who could benefit from treatment and whose symptoms affected their quality of
      life. In a population of 250,000, 482 men [95 per cent confidence interval (CI)
      263-704] could benefit from treatment in secondary care, and 3,557 men could be
      managed in primary care through watchful waiting or medical intervention (95 per
      cent CI 2,935-4,182). CONCLUSIONS: The majority of men with LUTS in the community
      are not greatly troubled by them and are unlikely to benefit from treatment. This
      work can be used as a basis for planning the provision of services across primary
      and secondary care for the treatment of this common condition.

PMID- 11450932
TI  - Developing principles for health impact assessment.
AB  - BACKGROUND: Policies and practice in many sectors affect health. Health impact
      assessment (HIA) is a way to predict these health impacts, in order to recommend
      improvements in policies to improve health. There has been debate about
      appropriate methods for this work. The Scottish Executive funded the Scottish
      Needs Assessment Programme to conduct two pilot HIAs and from these to develop
      guidance on HIA. METHODS: Case study 1 compared three possible future scenarios
      for developing transport in Edinburgh, based on funding levels. It used a
      literature review, analysis of local data and the knowledge and opinions of key
      informants. Impacts borne by different population groups.were compared using
      grids. Case study 2 assessed the health impacts of housing investment in a
      disadvantaged part of Edinburgh, using published literature, focus groups with
      community groups and interviews with professionals. RESULTS: Disadvantaged
      communities bore more detrimental effects from the low transport investment
      scenario, in the areas of: accidents; pollution; access to amenities, jobs and
      social contacts; physical activity; and impacts on community networks. The
      housing investment had greatest impact on residents' mental health, by reducing
      overcrowding, noise pollution, stigma and fear of crime. CONCLUSION: Although
      there is no single 'blueprint' for HIA that will be appropriate for all
      circumstances, key principles to inform future HIA were defined. HIA should be
      systematic; involve decision-makers and affected communities; take into account
      local factors; use evidence and methods appropriate to the impacts identified and
      the importance and scope of the policy; and make practical recommendations.

PMID- 11450933
TI  - NHS Direct: review of activity data for the first year of operation at one site.
AB  - BACKGROUND: NHS Direct was set up in 1998 and now covers all of England. One site
      in South East London, which went live in April 1999, has been studied to gain an
      insight into how NHS Direct is used and by whom. METHODS: Routine data from TAS
      was obtained from NHS Direct in South East London for its first year of
      operation. RESULTS: Data were collected on 56540 calls. Almost one-quarter of
      calls were for 0- to 5-year-olds. The service was busiest between 9 a.m. and 2
      p.m. and again between 6 p.m. and 9 p.m. The majority of calls (68 per cent) were
      received during the out-of-hours period. Most calls to the service (56 per cent)
      are categorized with no urgency level, with 37 per cent of callers given advice
      on how to look after the problem themselves. Over the millennium celebration
      period the call volume tripled. However, calls tended to be less urgent, with
      more being from the older age groups. CONCLUSION: NHS Direct is an important
      service to parents of young children and can provide advice about when contact
      with another service is necessary to those who traditionally worry about this.

PMID- 11450934
TI  - Quarterly communicable disease review. October to December 2000--from the PHLS
      Communicable Diseases Surveillance Centre.

PMID- 11450935
TI  - Health impact assessment of Merseyside Integrated Transport Strategy.

PMID- 11450936
TI  - Health impact assessment.

PMID- 11450937
TI  - The health of students.

PMID- 11450938
TI  - On health inequality.

PMID- 11450939
TI  - Sleep [editorial].

PMID- 11450940
TI  - Lessons from tobacco control for advocates of healthy transport.
AB  - Many parallels can be drawn between cigarettes and motor vehicles, smoking and
      car driving, and the tobacco and the auto/oil industries. Those promoting healthy
      and sustainable transport policies can learn lessons from tobacco control
      activities over the past 50 years. Evidence-based legislation is more effective
      than negotiated voluntary agreements between industry and government. Media
      advocacy is crucial to reframe the issues to allow changes in national policies
      that facilitate healthier choices. Worthwhile public health policies seen as a
      threat by multinational companies will be opposed by them but active national and
      international networks of healthcare professionals, voluntary organizations,
      charities and their supporters can match the political power of these industries.

PMID- 11450941
TI  - Public access defibrillation: a shocking idea?
AB  - Currently, survival from out-of-hospital cardiac arrest in the United Kingdom is
      poor. Ambulance response standards require that an ambulance reach 75 per cent of
      cardiac arrests within 8 min. But a short time to defibrillation from the onset
      of collapse is a key predictor of outcome from out-of-hospital cardiac arrest.
      The Department of Health has recently implemented a lay responder defibrillation
      programme, with the aim of shortening this time interval for victims in public
      places. This initiative utilizes automated external defibrillators (AEDs), which
      provide written and recorded voice prompts to minimize training requirements and
      errors in use. Lay responder AED programmes with very short response times have
      reported survival to discharge rates of up to 53 per cent for patients presenting
      in ventricular fibrillation (VF). This compares well with the results of a meta
      analysis that reported a survival rate of only 6.4 per cent for traditional
      defibrillator-equipped ambulance systems. The annual incidence of out-of-hospital
      cardiac arrest in England is 123 per 100,000 population. Approximately half of
      these present in VF, and could benefit from an AED programme. But only 16 per
      cent of cardiac arrests occur in a public place. It has been calculated that
      there are approximately 5,000 instances of VF in public places each year in
      England. If half of these patients can be reached and administered a first shock
      within 4 min of their collapse, an additional 400 victims may survive each year.
      Given the current investment by the DoH of 2 million pounds, this suggests a cost
      per life saved of approximately 505 pounds over a 10 year period.

PMID- 11450942
TI  - Diversity, distribution, and mobility of bro gene sequences in Bombyx mori
      nucleopolyhedrovirus.
AB  - Genetic differences between strains of a baculovirus are often limited to some
      restriction sites, short DNA deletions or absence of some nonessential genes. The
      recently coined bro gene family, represents a new major source of intraspecific
      variability. A comparison between two bro gene sets of Bombyx mori
      nucleopolyhedroviruses (NPV) shows that bro genes are distributed in three
      regions for the -T3 and -SC7 virus strains. In BmNPV T3, five bro genes are
      distributed in three genome locations, whereas the BmNPV SC7 strain possess a
      single bro copy in each region. In addition, each of the BmNPV SC7 bro genes
      belongs to one of the three subfamilies present in BmNPV T3. Analysis of bro copy
      sequences and of adjacent sequences suggests an active redistribution of
      sequences due to intraspecific recombination. The maintenance of one allele of
      each subfamily suggests that they play different roles in the viral cycle, and
      that they are essential.

PMID- 11450943
TI  - Identification and in vivo characterization of the Epiphyas postvittana
      nucleopolyhedrovirus Ecdysteroid UDP-glucosyltransferase.
AB  - The genome of Epiphyas postvittana Nucleopolyhedrovirus (EppoMNPV) contains an
      ecdysteroid UDP-glucosyltransferase (egt) gene. The egt gene was completely
      sequenced and surrounding open reading frames identified. EppoMNPV egt is 1479
      nucleotides in length encoding a protein with a predicted molecular mass of 55
      kDa. Analysis of upstream sequence revealed dual TATA boxes and two CGT upstream
      activating region motifs. Mapping of the 5' terminus of the egt transcript
      identified a major transcript produced from an adenine residue 29 nucleotides
      downstream from the distal TATA box. No transcript was detected from a late
      promoter motif (GTAAG). Characterization of egt transcripts showed that poly
      adenylation occurs at the 3' terminus. EppoMNPV egt transcripts were first
      detected in infected Epiphyas postvittana larvae by Northern hybridization at 9 h
      post-infection (hpi) and EGT enzyme activity was detected at 9 hpi in haemolymph
      from infected larvae. EppoMNPV EGT can conjugate the sugars from both UDP-glucose
      and UDP-galactose to ecdysone in vitro. Localization assays performed using
      radiolabelled ecdysone demonstrated that the conjugation of glucose or galactose,
      from the respective UDP-sugar, led to the prevention of the uptake of ecdysone by
      SF-21 cells. We propose that EGT functions to prevent the uptake of ecdysone or
      20-hydroxyecdysone by metabolite and target cells respectively.

PMID- 11450944
TI  - Analysis of the triple gene block and coat protein sequences of two strains of
      Kalanchoe latent carlavirus.
AB  - A region of the Kalanchoe latent carlavirus (KLV) genome, containing the coding
      capacity for the triple gene block and the coat protein, was cloned and sequenced
      for two isolates, the one infecting Chenopodium quinoa systemically whereas the
      other infects C. quinoa locally. The sequence confirmed the classification of KLV
      as a carlavirus. There was the highest identity in the amino acid sequences to
      the carlaviruses potato rough dwarf virus, lily latent virus, lily symptomless
      virus, blueberry scorch virus and potato virus S. The aminoacid sequences of
      proteins of the two KLV isolates had an identity between 86% and 91%.

PMID- 11450945
TI  - The non-structural leader protein gene of foot-and-mouth disease virus is highly
      variable between serotypes.
AB  - Aphthoviruses are unique among picornaviruses in that they alone encode a
      functional L proteinase as the first component of the viral polyprotein. The L
      genes of a few Indian foot-and-mouth disease viruses were sequenced and compared
      with those available to study the extent of variation in this gene. Besides the
      two in-frame start codons present in all FMDV L genes, the Asia-I vaccine virus
      had an additional in-frame AUG (start) codon, at codon position 3. Amino acid
      sequence comparison revealed that 39.8% of positions were capable of accepting
      replacements, yet the residues of the catalytic dyad were totally conserved.
      Sequence comparison at the C-terminus of the protein indicated that K/R
      decreasing GAGQS is sufficient for L/P1 cleavage. Phylogenetic analysis based on
      the L gene sequences did not reveal any serotype-specific clustering. The
      probable implications of the observed high variability in this non-structural
      gene is briefly discussed.

PMID- 11450946
TI  - Human T-cell leukemia virus type I tax protein induces the expression of anti
      apoptotic gene Bcl-xL in human T-cells through nuclear factor-kappaB and c-AMP
      responsive element binding protein pathways.
AB  - Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T
      cell leukemia (ATL), which is an aggressive form of human T-cell malignancy. The
      viral protein, Tax, immortalizes human T-cells and inhibits various types of
      apoptosis, and is thought to play crucial roles in the development of ATL. We
      have recently demonstrated that Tax induces the constitutive expression of the
      anti-apoptotic protein, Bcl-xL, in a mouse T-cell line. The mouse, however, is
      not a natural host of HTLV-I, and HTLV-I does not induce this malignancy in mice.
      We thus examined whether Tax also activates the expression of Bcl-xL in human T
      cells. Expression of Tax in a human T-cell line, Jurkat, induced the expression
      of the Bcl-xL gene, but did not significantly affect the expression of the other
      apoptosis-related genes, Bcl-2 and Bax. Transient transfection assays showed that
      Tax stimulated human Bcl-xL promoter activity in Jurkat cells. Deletion of the
      two potential nuclear factor (NF)-kappaB binding sites in the human Bcl-xL
      promoter significantly decreased Tax-induced transactivation. In addition to NF
      kappaB, Tax activates transcription through the c-AMP responsive element binding
      protein (CREB). Tax mutants segregating these two pathways showed that both the
      NF-kappaB and CREB pathways of Tax are required for maximum activation of a human
      Bcl-xL promoter, nevertheless, NF-kappaB alone was sufficient for that of a mouse
      Bcl-xL promoter. Northern blot analysis showed that all the human T-cell lines
      expressing Tax had higher levels of Bcl-xL mRNA than HTLV-I-uninfected ones.
      Furthermore, the sample from one patient with ATL expressed higher levels of Bcl
      xL mRNA compared with levels from uninfected peripheral blood mononuclear cells.
      Our results suggest that Tax induces the expression of Bc-xL through the NF
      kappaB and CREB pathways in HTLV-I-infected human T-cells, and then inhibits
      apoptosis, and such inhibition is necessary for the infected cells to advance to
      the leukemia in vivo.

PMID- 11450947
TI  - Identification and characterization of segments 3 and 4 of the ISAV genome.
AB  - Infectious Salmon Anaemia is a serious disease of farmed Atlantic Salmon on three
      continents. The disease causes severe anaemia and haemorrphagic liver necrosis,
      and carries major economic consequences for affected areas. Nevertheless, the
      causative agent, a novel orthomyxo-like Virus (Infectious Salmon Anaemia Virus -
      ISAV), is only partially characterized at the molecular level. We report the
      isolation and characterization of two novel ISAV segments at the genomic and
      proteomic levels. These segments are the third and fourth largest of the (ISAV)
      genome and may code for a nucleocapsid protein (NP) and a polymerase (PA).
      Western blot analysis using an ISAV polyclonal antibody identified one of these
      novel proteins as being the major tissue antigen. We discuss the implications of
      our findings for vaccine development and surveillance of Infectious Salmon
      Anaemia.

PMID- 11450948
TI  - The downstream activation sequence of the strict late Herpes Simplex Virus Type 1
      U(L)38 promoter interacts with hTAF(II)70, a component of TFIID.
AB  - A class of strict late Herpes Simplex Virus Type 1 (HSV-1) promoters contains a
      conserved sequence element (termed the downstream activation sequence, DAS)
      located downstream of the transcription start site. These DAS-containing
      promoters also require both a TATA box and an initiator element for maximal
      levels of transcription. In this communication, we demonstrate that the
      downstream promoter element (DPE) found on a class of Drosophila TATA-less
      promoters and known to bind the homologue of human TAF(II)70 (a component of
      TFIID), can functionally substitute for DAS in the context of the strict late
      UL38 promoter in spite of no obvious sequence similarity. Although Drosophila DPE
      containing promoters do not require a TATA box, the element does not remove the
      requirement for a TATA box when functioning in the HSV promoter. Next, we
      demonstrate that hTAF(II)70, interacts in a sequence specific manner with DAS as
      predicted from the fact that DPE binds Drosophila TBP. These results suggest that
      multiple TFIID/promoter interactions are important in the activation of HSV-1
      late gene expression upon viral DNA replication. We propose that such
      interactions could be favored upon viral DNA replication since TFIID concentrates
      to viral transcription foci that form during the later stages of infection.

PMID- 11450949
TI  - The helper virus envelope glycoprotein affects the disease specificity of a
      recombinant murine leukemia virus carrying a v-myc oncogene.
AB  - Many retroviruses that carry oncogenes (acute transforming viruses) are generally
      replication-defective and therefore require co-infection with a replication
      competent 'helper' retrovirus for infectivity. The helper virus provides the
      retroviral proteins necessary for particle production and infection. These
      include the envelope glycoproteins that specifically bind to cell surface
      receptors and mediate viral adsorption and entry. Thus, a particular helper virus
      may influence the nature of disease induced by an oncogene-containing retrovirus
      due to tissue tropism of the helper. In a previous study, a replication-defective
      recombinant Moloney murine leukemia virus containing the v-myc oncogene was
      generated (M-MuLV(myc); Brightman B.K., Pattengale P.K., and Fan H., J Virol 60:
      68-81, 1986). When M-MuLV(myc) was inoculated into mice using the non-pathogenic
      amphotropic murine leukemia virus (Am-MuLV 4070) as a helper, T- and B
      lymphoblastic lymphomas resulted with the following two surface phenotypes,
      namely, (1) Thy 1.2+, B220- and (2) Thy 1.2-, B220+. Thy 1.2 surface antigen is
      characteristic of cells of the lymphoid lineage, whereas B220 surface antigen is
      characteristic of cells of the B-lymphoid lineage. In these experiments, to
      assess the influence of the helper virus on the disease specificity of M
      MuLV(myc), two weakly pathogenic ecotropic helper MuLVs that interact with
      different cell surface receptors than Am-MuLV (Mo+PyF101 and AKV MuLV) were used
      to pseudotype M-MuLV(myc). In both cases, when inoculated into mice, these
      pseudotypes induced only T-lymphoblastic lymphoma. These results indicate that
      for M-MuLV(myc) the types of the tumors induced are influenced by the helper
      virus utilized, and they suggest that different lymphoid cells may express
      different levels of retroviral receptors.

PMID- 11450950
TI  - Identification and characterization of the UL24 gene product of herpes simplex
      virus type 2.
AB  - The UL24 gene of herpes simplex virus type 2 (HSV-2) is predicted to encode a 281
      amino acid protein with a molecular mass of 30.5 kDa. In this study, the HSV-2
      UL24 gene product has been identified by using a rabbit polyclonal antiserum
      produced against a recombinant protein containing the full-length UL24 gene
      product of HSV-2 fused to glutathione-S-transferase. The antiserum reacted
      specifically with a 32 kDa protein in HSV-2 186-infected Vero cells and with 31
      and 32 kDa proteins in UL24-expressing Cos-7 cells. Accumulation of UL24 protein
      to detectable levels required viral DNA synthesis, indicating that the protein
      was regulated as a late gene. UL24 protein was found to be associated with
      purified HSV-2 virions and C capsids. Indirect immunofluorescence analysis
      demonstrated that the UL24-specific fluorescence was detected in perinuclear
      regions of the cytoplasm and/or in the nucleus as small discrete granules from 9h
      post infection (hpi). Furthermore, the UL24 protein expressed singly was detected
      predominantly in the nucleus and slightly in the cytoplasm at 24 h after
      transfection, with branch-like cytoplasmic protruding structures. Strong
      nucleolus staining was visible in partial cells.

PMID- 11450951
TI  - Phylogenetic placement of a novel tenuivirus from the grass Urochloa plantaginea.
AB  - Evidence is presented that a tenuivirus recovered from the grass Urochloa
      plantaginea is probably a novel tenuivirus species, to be called Urochloa hoja
      blanca virus (UHBV). It is related to both Echinochloa hoja blanca virus (EHBV)
      and Rice hoja blanca virus (RHBV), and these three form a group distinct from
      Maize stripe virus (MStV) and Rice stripe virus (RStV). Phylogenetic analysis of
      the sequence data for RNA-3 and RNA-4 of these viruses supports the hypothesis
      that EHBV and UHBV may have evolved from an ancestral form of RHBV, precipitated
      by the introduction of Echinochloa colona and Urochloa plantaginea to America.

PMID- 11450952
TI  - Analysis of the P1 gene sequences and the 3'-terminal sequences and secondary
      structures of the single-stranded RNA genome of Potato virus V.
AB  - The immunocapture reverse transcriptase PCR method (IC-RT-PCR) was used to
      selectively amplify specific genome sequences of an isolate of Potato virus V
      (PVV, genus Potyvirus) from a potato plant infected by multiple viruses in the
      field in Finland. The sequences of the 5'- and 3'-non-translated regions (NTR)
      and the P1-and coat protein (CP)-encoding sequences were determined because they
      are the most variable genomic regions in potyviruses. The sequences of the new
      Finnish PVV isolate obtained in this study were compared to the sequences of
      eight PVV isolates characterized from other European countries. The results
      indicated little genetic variability among the European PVV isolates (nt identity
      values > 96% for all regions examined). Most PVV isolates were grouped according
      to their geographical origin using P1-sequences for a phylogenetic analysis. The
      nucleotide substitution patterns for P1 and the CP genes revealed that
      variability is due to a random genetic drift. Comparison of the secondary
      structure predictions for the unusually long 3'-non-translated region (3'-NTR) of
      PVV to the 3'-NTR of Tobacco etch virus (TEV) and other potyviruses revealed that
      some of the structures defining regions crucial for viral genome replication in
      TEV are present in PVV and other potyviruses.

PMID- 11450953
TI  - Molecular epidemiology of serotype O foot-and-mouth disease virus with emphasis
      on West and South Africa.
AB  - Genetic relationships of serotype O foot-and-mouth disease (FMD) viruses
      recovered from outbreaks of the disease in the West African countries of Niger,
      Burkina Faso and, Ghana (1988-1993) and those from South Africa (2000) were
      determined by partial VP1 gene characterization. A 581-bp fragment, corresponding
      to the C-terminus half of the ID (VP1 gene) region was amplified and sequenced.
      An homologous region of 495 nucleotides was ultimately used to determine genetic
      relationships of serotype O viruses from the Middle East, Europe, South America,
      North Africa, East Africa, southern Africa and Asia. Seven distinct type O
      genotypes were identified by phylogenetic reconstruction, consisting of viruses
      from the following geographical regions: Genotype A: Asia, the Middle East, and
      South Africa, Genotype B: East Africa, Genotype C: West and North Africa,
      Genotype D: Taiwan and Russia, Genotype E: Angola and Venezuela, Genotype F:
      Western Europe, and Genotype G: Europe and South America. The genotypes
      constitute three different evolutionary lineages (I-III), which correspond to
      three discrete continental regions, some of which display inter-continental
      distributions due to introductions. Results further indicate that the outbreaks
      in Burkina Faso (1992) and Ghana (1993) are part of the same epizootic and that
      the strain involved in a recent outbreak of the disease in South Africa is most
      closely related (97% sequence identity) to a 1997 Bangladesh strain.

PMID- 11450954
TI  - Characterization of a recombinant fowlpox virus expressing the native hexon of
      hemorrhagic enteritis virus.
AB  - The structure of the icosahedral adenovirus capsid is highly conserved among
      Adenoviridae. In its native form, the hexon is the major capsid protein. The
      nascent hexon requires the 100 kDa folding protein to fold into its native,
      trimeric form. The hexon and 100 kDa folding protein were co-expressed in a
      fowlpox virus (FPV) vector and in the recombinant FPVs (rFPVs) in which the hexon
      and 100 kDa folding protein genes are cloned head to tail, the native hexon could
      be detected with indirect immunofluorescence and immunoprecipitation using a
      native hexon monoclonal antibody. The FPV-@X100 construct, in which the 100kDa
      folding protein gene follows the hexon gene in a head to tail fashion, elicited
      the best humoral response in chickens. An attenuated HEV commercial vaccine
      elicited higher and longer lasting anti-HEV titers than FPV-@X100. Humoral
      immunity was also compared in turkeys inoculated with rFPVs expressing the hexon
      alone, the 100 kDa folding protein alone, or expressing both genes in different
      configurations. No anti-HEV humoral immune response was detected in turkeys
      inoculated with the rFPVs expressing the hexon alone or the 100 kDa folding
      protein alone.

PMID- 11450955
TI  - Generation of a recombinant Anticarsia gemmatalis multicapsid
      nucleopolyhedrovirus expressing a foreign gene under the control of a very late
      promoter.
AB  - A recombinant Anticarsia gemmatalis multicapsid nucleopolyhedrovirus (AgMNPV)
      expressing beta-galactosidase under the control of the polyhedrin promoter was
      generated in our laboratory. To this end, we cloned the AgMNPV-2D genomic DNA
      fragment containing the polh gene and subcloned and sequenced the polyhedrin gene
      and its flanking regions. Based on this sequence information, sets of primers
      were designed to amplify the flanking regions by PCR, including appropriate
      restriction sites. The transfer vector (pAgPHZ) was constructed by the
      consecutive cloning of these PCR fragments flanking the Escherichia coli LacZ
      gene, in place of the polh gene. pAgPHZ was used for cotransfection of UFL-AG-286
      insect cells with AgMNPV-2D DNA and the required recombinant, generated by
      homologous recombination with the polh locus, was identified by its polh(-)/LacZ+
      plaque phenotype. Its genome structure was confirmed by PCR, restriction
      digestion and Southern blot analyses. The kinetics and levels of expression of
      beta-galactosidase in UFL-AG-286 cells infected with the recombinant were tested
      by SDS-PAGE and enzymatic activity assays.

PMID- 11450956
TI  - MR spectroscopy: Clinical tool or research probe? (revisited).

PMID- 11450957
TI  - Enhancement of hyperglycemia-induced acidification of human melanoma xenografts
      with inhibitors of respiration and ion transport.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the
      selective acidification of a human melanoma xenograft in mice with severe
      combined immunodeficiency with the induction of hyperglycemia (mean blood glucose
      level +/- standard error of the mean, 26 mmol/L +/- 1) and the intraperitoneal
      administration of metaiodobenzylguanidine (MIBG, 30 mg/kg), alpha-cyano-4
      hydroxycinnamate (CNCn, 300 mg/kg), lonidamine (100 mg/kg), cariporide (HOE642,
      160 mg/kg), or 4.4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS, 50
      mg/kg). MATERIALS AND METHODS: The intra- and extracellular pH levels of tumor
      were estimated from the chemical shifts of inorganic phosphate and 3
      aminopropylphosphonate, respectively, with phosphorus-31 nuclear magnetic
      resonance (MR) spectroscopy. The relative level of steady-state lactate was
      monitored with hydrogen-1 MR spectroscopy. RESULTS: In small tumors (< or = 8.0
      mm), hyperglycemia decreased the intra- and extracellular pH levels by less than
      0.2. The combination of hyperglycemia and MIBG decreased the intra- and
      extracellular pH levels by approximately 0.4 and 0.6, respectively, and lowered
      the beta-nucleoside triphosphate (NTP)/inorganic phosphate (Pi) ratio of tumor
      and liver by about 60% and 25%, respectively. The combination of hyperglycemia,
      MIBG, and CNCn produced a transient decrease in the intracellular pH of about
      0.6. The combination of hyperglycemia and lonidamine produced a sustained (>3
      hours) 0.8-unit decrease in intracellular pH and an 83% and 100% decrease in
      PCr/P1 and beta-NTP/P1 ratios, respectively. The combination of hyperglycemia.
      MIBG, cariporide, and DIDS produced a gradual decrease in intra- and
      extracellular pH by 1.1 and 1.0, respectively. The relative level of steady-state
      lactate concentration in tumors increased 10% with hyperglycemia alone, about 20%
      with MIBG plus hyperglycemia, and increased more than twofold when hyperglycemia
      was combined with MIBG and CNCn administration. CONCLUSION: These preliminary
      data suggest that hyperglycemia and combinations of respiratory and ion transport
      inhibitors can be used to selectively acidify tumors and, thereby, sensitize them
      to hyperthermnia or other pH-sensitive therapeutic modalities.

PMID- 11450958
TI  - Validation of in vivo MR measurement of oxygen saturation after resuscitation
      with a hemoglobin-based oxygen carrier in a rabbit model.
AB  - RATIONALE AND OBJECTIVES: The authors tested whether noninvasive magnetic
      resonance (MR) oximetry is accurate in the in vivo measurement of oxygen
      saturation in a stroma-free, hemoglobin-based oxygen carrier (HBOC). MATERIALS
      AND METHODS: A central venous catheter was placed in the inferior vena cava (IVC)
      of 10 New Zealand white rabbits (weight range, 2.5-3.2 kg). Each rabbit underwent
      removal of 20% of blood volume followed by resuscitation with 10 mL/kg of bovine
      HBOC-200. Oxygen saturation of the blood mixture was measured in vivo at the IVC
      with MR oximetry, with separate in vitro calibration for each animal. Blood drawn
      from the IVC was measured with ex vivo oximetry, which was used as the standard
      of reference. The in vivo and ex vivo measurements were compared. RESULTS: There
      was no significant difference (P > .1) between measurements obtained with MR
      oximetry and ex vivo oximetry. The results with in vivo MR oximetry demonstrated
      excellent correlation with those from ex vivo oximetry (r = 0.99) over a wide
      range of physiologic oxygen saturation values (16.7%-74.9%) in venous blood.
      CONCLUSION: Noninvasive in vivo MR measurement of oxygen saturation is valid for
      whole blood mixed with stroma-free hemoglobin. Therefore, MR oximetry may be
      clinically useful for assessing the oxygenation status in patients resuscitated
      with a HBOC.

PMID- 11450959
TI  - A combined architectural and kinetic interpretation model for breast MR images.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to integrate contrast
      material kinetic and architectural data from magnetic resonance (MR) images and
      to assess the improvement in diagnostic accuracy. MATERIALS AND METHODS: MR
      imaging data from a diagnostic cohort of 100 patients (50 malignant and 50 benign
      cases) were analyzed. RESULTS: Qualitative classification of the enhancement
      curve was the most predictive kinetic feature. Receiver operating characteristic
      (ROC) curves were calculated for the architectural model alone and for the
      architectural model combined with the qualitative kinetic classification. The
      results demonstrated a statistically significant increase in ROC area (P = .03)
      of the combined model compared with that of the architectural model alone.
      CONCLUSION: The addition of qualitative classification of the time-signal
      intensity curve to an architectural interpretation model results in significant
      improvement in model performance as measured by the area under the ROC curve.

PMID- 11450960
TI  - Functional MR imaging of vision in the deaf.
AB  - RATIONALE AND OBJECTIVES: Early loss of a sensory modality has been associated
      with cortical reorganization in both animal models and humans. The purpose of
      this study was to map visual activation with functional magnetic resonance (MR)
      imaging and to document possible developmental reorganization in the temporal
      lobe caused by early deafness. MATERIALS AND METHODS: Six prelingual, profoundly
      deaf subjects were compared with a similar group of six hearing subjects. Three
      visual tasks were performed by both groups: attention to movement in the field-of
      view periphery, shape matching, and mental rotation. Echo-planar coronal MR
      imaging was performed at 1.5 T. RESULTS: Regions of interest encompassing the
      middle and posterior aspects of the superior and middle temporal gyri
      demonstrated a significantly (P < .05) increased activation in deaf subjects
      compared with hearing subjects, particularly on the right side (P < .05) and
      during the tasks involving motion. The most specific effect was noted during the
      mental-rotation task. CONCLUSION: These results support the hypothesis that
      portions of the temporal lobe usually involved in auditory processing are more
      active during certain visual tasks in deaf compared with hearing subjects.
      Cortical reorganization may be an important factor in the deaf population when
      considering the physiology of temporal lobe lesions and predicting surgical
      outcomes. Functional MR imaging may be helpful during preoperative assessment in
      individuals with deafness.

PMID- 11450961
TI  - Components-of-variance models for random-effects ROC analysis: the case of
      unequal variance structures across modalities.
AB  - RATIONALE AND OBJECTIVES: Several of the authors have previously published an
      analysis of multiple sources of uncertainty in the receiver operating
      characteristic (ROC) assessment and comparison of diagnostic modalities. The
      analysis assumed that the components of variance were the same for the modalities
      under comparison. The purpose of the present work is to obtain a generalization
      that does not require that assumption. MATERIALS AND METHODS: The generalization
      is achieved by splitting three of the six components of variance in the previous
      model into modality-dependent contributions. Two distinct formulations of this
      approach can be obtained from alternative choices of the three components to be
      split; however, a one-to-one relationship exists between the magnitudes of the
      components estimated from these two formulations. RESULTS: The method is applied
      to a study of multiple readers, with and without the aid of a computer-assist
      modality. performing the task of discriminating between benign and malignant
      clusters of microcalcifications. Analysis according to the first method of
      splitting shows large decreases in the reader and reader-by-case components of
      variance when the computer assist is used by the readers. Analysis in terms of
      the alternative splitting shows large decreases in the corresponding modality
      interaction components. CONCLUSION: A solution to the problem of multivariate ROC
      analysis without the assumption of equal variance structure across modalities has
      been provided. Alternative formulations lead to consistent results related by a
      one-to-one mapping. A surprising result is that estimates of confidence intervals
      and numbers of cases and readers required for a specified confidence interval
      remain the same in the more general model as in the restricted model.

PMID- 11450962
TI  - Analysis of uncertainties in estimates of components of variance in multivariate
      ROC analysis.
AB  - RATIONALE AND OBJECTIVES: Solutions have previously been presented to the problem
      of estimating the components of variance in the general linear model used for
      multivariate receiver operating characteristic (ROC) analysis. The case where the
      variance components do not change across the modalities under comparison was
      first treated, followed by the case where they are permitted to change. No
      analysis of uncertainties in these estimates has been presented previously.
      MATERIALS AND METHODS: For the case where the variance components do not change
      across modalities, the "jackknife-after-bootstrap" resampling procedure can be
      used together with conventional linear propagation of variance to solve for the
      uncertainties in estimates of the components. For the case where the components
      are permitted to change across modalities, a slight elaboration of this procedure
      is presented. RESULTS: The approach was validated by Monte Carlo simulations,
      where uncertainties in estimates of the variance components calculated by the
      jackknife-after-bootstrap procedure were found to converge in the mean to the
      Monte Carlo results over many independent trials. The method is exemplified with
      data from a study of readers-with and without the aid of a computer-assist
      modality-given the task of discriminating benign from malignant masses in
      mammography. CONCLUSION: The present approach is relevant to a broad class of
      problems where estimates of multiple contributions to the variance observed in
      ROC assessment of diagnostic modalities are desired, in particular, for the
      assessment of multiple-reader studies of computer-aided diagnosis in radiology
      where the variance components may change across reading modalities (eg, unaided
      vs computer-aided reading).

PMID- 11450963
TI  - In vitro evaluation of the effectiveness of distal protection in the prevention
      of cerebral thromboembolism during carotid stent placement.
AB  - RATIONALE AND OBJECTIVES: The purpose of this in vitro study was to evaluate and
      quantify the benefit of the balloon protection device, to identify the most
      effective sequence of irrigation or flushing, and to determine the most effective
      catheter position to remove the maximum number of emboli or debris beneath the
      flow-arrest balloon. MATERIALS AND METHODS: Silicone models of the
      neurovasculature were attached to a systodiastolic pump. Stents were placed in
      carotid stenoses by using the distal flow protection technique. Embolic material
      was released within the stent. The effectiveness of different irrigation
      techniques was evaluated. RESULTS: Aspiration under the balloon through the
      guiding catheter with a 60-mL syringe followed by one power injection at 40 mL
      injected at 2 mL/sec will result in removal of about 98% of potential emboli from
      the internal carotid artery [corrected]. CONCLUSION: In vitro evaluation of the
      distal flow protection technique indicates that it should reduce stroke risk
      during carotid stent placement.

PMID- 11450964
TI  - Improved method for automatic identification of lung regions on chest
      radiographs.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate an
      algorithm developed to help identify lungs on chest radiographs. MATERIALS AND
      METHODS: Forty clinical posteroanterior chest radiographs obtained in adult
      patients were digitized to 12-bit gray-scale resolution. In the proposed
      algorithm, the authors simplified the current approach of edge detection with
      derivatives by using only the first derivative of the horizontal and/or vertical
      image profiles. In addition to the derivative method, pattern classification and
      image feature analysis were used to determine the region of interest and lung
      boundaries. Instead of using the traditional curve-fitting method to delineate
      the lung, the authors applied an iterative contour-smoothing algorithm to each of
      the four detected boundary segments (costal, mediastinal, lung apex, and
      hemidiaphragm edges) to form a smooth lung boundary. RESULTS: The algorithm had
      an average accuracy of 96.0% for the right lung and 95.2% for the left lung and
      was especially useful in the delineation of hemidiaphragm edges. In addition, it
      took about 0.775 second per image to identify the lung boundaries, which is much
      faster than that of other algorithms noted in the literature. CONCLUSION: The
      computer-generated segmentation results can be used directly in the detection and
      compensation of rib structures and in lung nodule detection.

PMID- 11450965
TI  - Inpatient costs of routine endovascular repair of abdominal aortic aneurysm.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the
      inpatient cost of routine (ie, without emergent conversion to open repair during
      the hospital stay) endovascular stent-graft placement in a consecutive series of
      patients undergoing elective endovascular repair of abdominal aortic aneurysm
      (AAA) at a single institution. MATERIALS AND METHODS: Inpatient hospital costs of
      91 patients who underwent initial elective endovascular repair of AAA were
      analyzed retrospectively. All patients had participated in clinical trials at the
      authors' institution during the previous 6 years. Financial data were derived
      from the hospital's cost-accounting system; additional procedural data were
      collected from a departmental database and with chart review. Stent-graft and
      professional costs were excluded. RESULTS: The mean total cost for endovascular
      repair was $11,842 (standard deviation [SD], $5,127), mean procedure time was 149
      minutes (SD, 79 minutes), and mean length of stay was 3.5 days (SD, 2.3 days).
      Total cost depended on stent-graft type (means, $12,428 [bifurcated] vs $9,622
      [tube]; P = .0002) and strongly correlated with procedure time and length of
      hospital stay (r = 0.78 and 0.66, respectively; P < .0001). Ninety-six percent of
      total costs for all patients were attributable to the following departments:
      operating theater (31%), radiology (31%), nursing (22%), and anesthesia (12%).
      CONCLUSION: Overall costs are greater with bifurcated than with tube stent
      grafts. Total procedure-related costs are divided relatively equally between the
      operating theater, the radiology department, and the combination of the nursing
      and anesthesia departments.

PMID- 11450966
TI  - Effect of training with the american college of radiology breast imaging
      reporting and data system lexicon on mammographic interpretation skills in
      developing countries.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the effect of training in the
      American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI
      RADS) lexicon on the interpretive skills of radiologists evaluating screening
      mammograms in Ukraine. MATERIALS AND METHODS: As part of a program to improve
      breast cancer detection and treatment in Ukraine, a series of training sessions
      was given to a group of radiologists across Ukraine to improve their interpretive
      skills in screening mammography. The training sessions focused on the use of the
      lexicon and assessment categories developed by the ACR BI-RADS committee.
      Participants (n = 14) evaluated 30 test screening mammograms before and after the
      training sessions. The test sets were randomly selected from a larger collection
      of training sets containing normal, benign, and abnormal mammograms. False
      positive, false-negative, true-positive, and true-negative evaluations were
      determined, and sensitivity, specificity, and positive predictive values were
      calculated for each participant before and after training. RESULTS: The mean
      baseline sensitivity, specificity, and positive predictive values were 50%, 77%,
      and 43%, respectively. Each of these measures of interpretive skills improved
      significantly after training in the use of the lexicon, to 87%, 89%, and 78% (P <
      .0001, P < .01, and P < .0001, respectively). CONCLUSION: As the use of
      mammography spreads throughout developing countries, it is essential to address
      training and educational needs, as well as equipment needs. The ACR BI-RADS
      lexicon provides a systematic and efficient method for training radiologists to
      interpret screening mammograms. Educating radiologists on the use of this lexicon
      proved an effective way to improve their interpretive skills in screening
      mammography.

PMID- 11450967
TI  - A vital skill for radiologic education.

PMID- 11450968
TI  - Maintaining consultation skills in today's practice environment.

PMID- 11450969
TI  - Radiologists as clinical tutors in a problem-based medical school curriculum.
AB  - RATIONALE AND OBJECTIVES: The authors sought to evaluate the experience of
      radiologists teaching in a problem-based pre-clinical medical school curriculum.
      MATERIALS AND METHODS: The undergraduate medical school curriculum at Wake Forest
      University includes 2 problem-based preclinical years that integrate basic and
      clinical sciences. Sixteen radiology fellows served as general clinical tutors
      for 5-9 weeks, each guiding the work of six 2nd-year students, often in tandem
      with a basic science tutor. On completion of the tutoring. the radiologists and
      the students were surveyed by means of a questionnaire. A follow-up group
      interview was conducted with the radiologists. RESULTS: The response rate to the
      questionnaire was 81% for the radiologists and 47% for the students. On average,
      radiologists spent 6.1 hours weekly on preparation and tutoring and 3.5 hours in
      total on administration and grading. All radiologists thought tutoring was
      rewarding, but seven of the 13 respondents (54%) disliked assigning grades.
      Radiologists spent less time teaching radiology residents and performing
      research, but few thought their clinical work was adversely affected. Nearly half
      of the radiologist-tutors thought that the preliminary orientation and training
      provided to them by the medical school was not adequate, and nearly all of them
      thought that they could have been better prepared. All of the medical students
      improved their perceptions of radiologists after having had a radiologist as a
      tutor, and most thought that the radiologist-tutors performed as well as or
      better than tutors from other disciplines. CONCLUSION: Radiologists can be
      successful as general tutors in a problem-based medical school curriculum.
      benefiting both radiologists and students. Better orientation and training by the
      medical school would improve the program.

PMID- 11450970
TI  - NCI image archive management workshop: a preliminary report.
AB  - The National Cancer Institute organized a workshop entitled "Image Archive
      Management" that was presented on August 28 and 29, 2000, at the Natcher
      Conference Center on the National Institutes of Health (NIH) campus. The purpose
      of this workshop was to solicit expert input for the planned development of an
      archival system to make imaging databases readily accessible by the broad
      scientific community. The specific goals were to (a) define the technical
      requirements for a virtual archive of images used in oncology, (b) define the
      policy issues for access to these images, (c) recommend a process and phases for
      implementation of a robust imaging archival system, (d) review how this effort
      could be expanded and coupled with other ongoing efforts by NIH and other
      organizations interested in imaging, and (e) form an overall plan and policy to
      allow interoperability of image data archives. Representatives who attended the
      workshop came from academia, government agencies, and large and small businesses.
      A preliminary report was generated, as outlined herein, and additional reports
      are anticipated from the steering committee being organized as one of this
      workshop's recommendations, which is expected to be active by summer 2001.
      Additional information, including the list of participants in this workshop, is
      available at the Biomedical Imaging Program Web site
      (http://www.nci.nih.gov/bip/).

PMID- 11450971
TI  - Unraveling DNA repair in human: molecular mechanisms and consequences of repair
      defect.
AB  - Cellular genomes are vulnerable to an array of DNA-damaging agents, of both
      endogenous and environmental origin. Such damage occurs at a frequency too high
      to be compatible with life. As a result cell death and tissue degeneration, aging
      and cancer are caused. To avoid this and in order for the genome to be
      reproduced, these damages must be corrected efficiently by DNA repair mechanisms.
      Eukaryotic cells have multiple mechanisms for the repair of damaged DNA. These
      repair systems in humans protect the genome by repairing modified bases, DNA
      adducts, crosslinks and double-strand breaks. The lesions in DNA are eliminated
      by mechanisms such as direct reversal, base excision and nucleotide excision. The
      base excision repair eliminates single damaged-base residues by the action of
      specialized DNA glycosylases and AP endonucleases. Nucleotide excision repair
      excises damage within oligomers that are 25 to 32 nucleotides long. This repair
      utilizes many proteins to remove the major UV-induced photoproducts from DNA, as
      well as other types of modified nucleotides. Different DNA polymerases and
      ligases are utilized to complete the separate pathways. The double-strand breaks
      in DNA are repaired by mechanisms that involve DNA protein kinase and
      recombination proteins. The defect in one of the repair protein results in three
      rare recessive syndromes: xeroderma pigmentosum, Cockayne syndrome, and
      trichothiodystrophy. This review describes the biochemistry of various repair
      processes and summarizes the clinical features and molecular mechanisms
      underlying these disorders.

PMID- 11450972
TI  - The mitochondrial import machinery for preproteins.
AB  - Most mitochondrial proteins are transported from the cytosol into the organelle.
      Due to the division of mitochondria into an outer and inner membrane, an
      intermembrane space and a matrix, an elaborated system for recognition and
      transport of preproteins has evolved. The translocase of the outer mitochondrial
      membrane (TOM) and the translocases of the inner mitochondrial membrane (TIM)
      mediate these processes. Receptor proteins on the cytosolic face of mitochondria
      recognize the cargo proteins and transfer them to the general import pore (GIP)
      of the outer membrane. Following the passage of preproteins through the outer
      membrane they are transported with the aid of the TIM23 complex into either the
      matrix, inner membrane, or intermembrane space. Some preprotein families utilize
      the TIM22 complex for their insertion into the inner membrane. The identification
      of protein components, which are involved in these transport processes, as well
      as significant insights into the molecular function of some of them, has been
      achieved in recent years. Moreover, we are now approaching a new era in which
      elaborated techniques have already allowed and will enable us to gather
      information about the TOM and TIM complexes on an ultrastructural level.

PMID- 11450973
TI  - Tension-Free vaginal tape (TVT) in stress incontinent women with intrinsic
      sphincter deficiency (ISD)--a long-term follow-up.
AB  - In a prospective long-term study 49 women with stress incontinence and ISD
      (intrinsic sphincter deficiency) were followed for a mean of 4 years (range 3-5)
      after TVT operation. Preoperatively all patients underwent urodynamic
      investigations, quality of life evaluation, a 24-hour pad test and a gynecologic
      examination to properly verify the incontinence symptoms. The same protocol was
      used for postoperative evaluation. The mean age of the women was 66 years (+/-
      11) and mean parity 2 (range 0-4). A standard TVT operation was performed under
      local anesthesia. At the postoperative evaluations 36 patients (74%) were
      completely cured of their incontinence problems. In addition, 6 women (12%) were
      significantly improved. In 7 patients (14%) no improvement was found. The
      majority of these not cured patients were >70 years of age and had urethral
      resting pressure of <10 cmH2O. Few intra- and postoperative complications
      occurred. It is concluded that TVT can be used for surgical treatment of patients
      with ISD and stress incontinence. However, older patients (>70 years) with a very
      low resting urethral pressure and an immobile urethra seem to constitute a risk
      group where TVT surgery is less successful.

PMID- 11450974
TI  - Tension-Free vaginal tape (TVT) in women with mixed urinary incontinence--a long
      term follow-up.
AB  - In a prospective long-term study we evaluated the effect of TVT surgery in 80
      women suffering from mixed urinary incontinence. Their mean age was 59 +/- 11
      years with a mean parity of 2 (range 0-6). Mean follow-up was 4 years (range 3
      5). The preoperative evaluation included a 24-hour pad test, quality of life
      evaluation, gynecologic examination and urodynamic investigations, including
      simultaneous urethrocystometry. From the patient history 96 patients were
      initially tentative candidates for TVT operation. Sixteen of these had only minor
      symptoms and signs of stress incontinence but significant symptoms and signs of
      detrusor instability, and were not considered suitable for TVT surgery. In the
      remaining 80 women the urodynamic investigation with filling urethrocystometry
      demonstrated stress incontinence and urge incontinence concomitant with urethral
      relaxation and/or 'premature micturition' reflex. At the postoperative long-term
      follow-up 85% of the patients were completely cured. Another 4% were
      significantly improved. In 11% of the patients the operation failed. Few intra-
      or postoperative complications occurred. Based on these results, we conclude that
      TVT surgery can be used for treatment of female mixed urinary incontinence. A
      proper urodynamic assessment is recommended before surgery is performed.

PMID- 11450975
TI  - Influence of different sling materials on connective tissue metabolism in stress
      urinary incontinent women.
AB  - The aim of this study was to investigate the influence on the paraurethral
      connective tissue of different sling materials used in incontinence surgery.
      Biopsies from the paraurethral connective tissue were obtained intraoperatively
      from 16 women with stress urinary incontinence; all were operated on with the TVT
      procedure, 6 with Mersilene as the sling material and 10 with Prolene. Biopsies
      from 4 continent women with uterine bleeding irregularities, matched for age and
      parity, served as controls. New biopsies were obtained from all women after 2
      years. The biopsies were examined histologically and analyzed for collagen
      concentration and solubility. An obvious inflammatory reaction with a significant
      increase in collagen extractability by pepsin was identified in patients where
      Mersilene was used as the sling material. A minimal inflammatory reaction without
      a significant change in collagen solubility was found in the Prolene group. In
      the control group no inflammatory reaction was seen. Mersilene gave rise to a
      significant foreign-body reaction in the paraurethral connective tissue after
      surgery. Such a reaction was not found with Prolene.

PMID- 11450976
TI  - Tension-Free vaginal tape: analysis of outcomes and complications in 404 stress
      incontinent women.
AB  - The aim of this prospective multicenter study was to evaluate the safety and
      efficacy of tension-free vaginal tape (TVT) for the surgical treatment of female
      stress incontinence. Four hundred and four women underwent the TVT procedure.
      Their mean age was 57 years (range 31-83). The median follow-up time was 21
      months (range 12-35). The subjective and objective cure rates were 92% and 90%,
      respectively. Another 4% of the women were significantly improved by the
      procedure. Intra- and postoperative complications were few and included
      uneventful bladder perforations (6%), retropubic bleeding requiring surgery
      (0.5%), voiding difficulties (4%) in the postoperative course, and one obturator
      nerve injury. We conclude that the TVT procedure is associated with a high cure
      rate and a low morbidity.

PMID- 11450977
TI  - The Austrian tension-free vaginal tape registry.
AB  - In Austria a central registry for all TVT operations has been established in
      which more than 800 cases have so far been registered. The registry contains
      information on pertinent data on the operated patients and intra- and
      postoperative outcomes of the TVT surgery. No serious complications and no
      mortality have been registered until now.

PMID- 11450978
TI  - An introduction to tension-free vaginal tape (TVT)--a new surgical procedure for
      treatment of female urinary incontinence.

PMID- 11450979
TI  - Long-term results of the tension-free vaginal tape (TVT) procedure for surgical
      treatment of female stress urinary incontinence.
AB  - In a prospective long-term Nordic multicenter study, 90 consecutive patients who
      had a tension-free vaginal tape (TVT) operation performed because of stress
      urinary incontinence were evaluated according to a strict protocol after
      approximately 5 years (range 48-70 months). Eighty-five patients could be
      evaluated according to the protocol. Another 5 elderly patients had to be
      interviewed by telephone at the final check-up after 5 years. The study protocol
      involved pre- and postoperative objective and subjective evaluation. The median
      follow-up time was 56 months. Seventy-two of the 85 patients who were fully
      evaluated (84.7%) were both objectively and subjectively completely cured.
      Another 9 patients (10.6%) were significantly improved and 4 (4.7%) were regarded
      as failures. No patient complained of long-term voiding difficulties and there
      were no signs of defective healing or rejection of the tape material. All
      patients had suffered from primary stress incontinence, and 25 also had
      preoperative complaints of urge. In 14 of these (56%) the urge symptoms were
      relieved postoperatively. We conclude that the TVT procedure seems to fulfil the
      expectations of high long-term cure rates, as suggested in previous short-term
      reports.

PMID- 11450980
TI  - Tension-Free vaginal tape (TVT) in women with recurrent stress urinary
      incontinence--a long-term follow up.
AB  - In a prospective long-term follow-up study we evaluated the results of TVT
      surgery in 34 women with recurrent stress urinary incontinence in whom previous
      traditional surgical procedures had failed. The women were followed for a mean of
      4 years (range 3-5) after TVT surgery. The mean age was 58.9 +/- 10 years and the
      mean parity 2 (0-4). Pre- and postoperative evaluation was performed according to
      a protocol which included gynecologic examination, urodynamic investigations,
      quality of life evaluation and 24-hour pad test. According to the protocol 28
      patients (82%) were cured, 3 (9%) were significantly improved, and the operation
      failed in 3 cases (9%). There were no significant intra- or postoperative
      complications. All patients were operated on under local anesthesia with a short
      hospitalization and had no long-term postoperative voiding problems.

PMID- 11450981
TI  - Hydroxyl radical generation: the effect of bicarbonate, dioxygen and buffer
      concentration on pH-dependent chemiluminescence.
AB  - Enhanced chemiluminescence (CL) induced by HO* was detected using the primary
      enhancers luminol (Lum), isoluminol (ILum) and lucigenin (Luc), in the absence of
      HCO3-, at pH 9.5, 10.0 and 10.5 but not between pH 4.0 and 9.0. This was
      confirmed using nine different HO* generators. FeCl3/NTA/H2O2 was the only HO*
      generator that was able to generate singular HO* which was obtained entirely from
      the Fenton reaction. However, this was so only at pH 10.0 since at all other pHs
      multiple ROS were produced. This was confirmed by the chemical detection of the
      fluorescent hydroxylated product of terephthalic acid in the absence of O2. No
      HO* Lum-CL pH optima coincided with the O2*- mediated Lum-CL optima found at pH
      8.0 and 9.0. Bicarbonate had an enhancing effect on Lum-CL which was 70-2700% at
      pH 10.0 for the different HO* generators. This was due to the conversion of the
      radical-electron from HO* to CO3*-, making CL detection more efficient since less
      HO* were lost initially before detection. Methyl-cypridine-luciferin analogue
      (MCLA) elicited CL in the pH range 4.0-10.0 with the same set of generators in
      the absence of HCO3-. The iron-containing generators had their different MCLA-CL
      optima at pH 4.5, 5.0 or 6.0, excluding those overlapping with the O2(*-)
      mediated CL optima. The two copper-containing generators had optima at the same
      pHs, viz, 7.0 and 10.5. Again, FeCl3/NTA/H2O2 was the only HO* generator able to
      produce singular HO* by the Fenton reaction. However, whereas Lum-CL was able to
      detect singular HO* only at pH 10.0, MCLA-CL detected it at pH 5.0 and 5.5.
      Therefore, MCLA is the most suitable CL enhancer for physiological assessments
      since it is the most sensitive enhancer and has HO* CL optima nearer to
      physiological pH than the other probes. The HCO3- enhancement of MCLA-CL was even
      greater than that of Lum-CL, since increases of 114-fold and 37-fold,
      respectively, were obtained at these HO*-specific pH optima for FeCl3/NTA/H2O2.
      Therefore, bicarbonate concentration is as important a parameter as pH when the
      enhanced CL of a non-cellular system is determined. Hydrogen peroxide was not
      able to elicit CL directly but, due to trace metal contamination, it produced
      artifactual CL due to HO* formation. High H2O2 levels, which prevent spontaneous
      O2*- dismutation, helped to establish the overlapping pH optima of CL mediated by
      O2*- and HO* which were artifactually produced either by O2*- via H2O2 and trace
      metals or by perferryl intermediates, respectively. Due to spontaneous
      dismutation to H2O2, only 22% of the O2*- produced by HX/XO could be detected by
      enhanced CL.

PMID- 11450982
TI  - Antioxidant effect of capsaicin on lipid peroxidation in homogeneous solution,
      micelle dispersions and liposomal membranes.
AB  - The antioxidant activity of capsaicin (CAP) was measured in the oxidation of
      methyl linoleate (ML) in homogeneous solution, of ML micelles in aqueous
      dispersions and also of soybean phosphatidylcholine liposomal membrane, and was
      compared to that of alpha-tocopherol (alpha-TOH) which is one of the most
      important antioxidants in vivo. The reactivity of CAP toward galvinoxyl (a model
      phenoxyl radical) in acetonitrile solution was found to be much smaller than that
      of alpha-TOH, suggesting that the radical scavenging activity of CAP is much
      weaker than that of alpha-TOH. In fact, in homogeneous acetonitrile solution
      where the antioxidant activity is determined primarily by the chemical activity
      of the antioxidant toward peroxyl radicals, CAP inhibited the oxidation of ML
      much less efficiently than alpha-TOH and a clear induction period was not
      observed. The antioxidant activity of CAP was found to be about 60 times smaller
      than that of alpha-TOH in homogeneous solution. However, in micelle oxidation,
      the difference in antioxidant activity of the two antioxidants was much smaller
      than in homogeneous solution. Furthermore, in the membrane, CAP inhibited the
      oxidation almost as effectively as alpha-TOH. These results suggest that CAP can
      act as an antioxidant in the biomembrane.

PMID- 11450984
TI  - . . . -ome sweet -ome.

PMID- 11450983
TI  - An improved photochemical method for the rapid spectrophotometric detection of
      superoxide dismutase.
AB  - A sensitive and convenient method is described for estimating superoxide
      dismutase activity using a photochemical augmentation procedure. This method is
      applicable to both liquid assays and polyacrylamide gel electropherograms. The
      flux of superoxide is generated by illuminating a reaction mixture containing
      dianisidine and riboflavin by either a laser source or light from a fluorescent
      lamp. The oxidation of dianisidine, as sensitized by riboflavin, is enhanced by
      superoxide dismutase. The increase is linearly dependent on superoxide dismutase
      concentration. The photochemical reaction is allowed to proceed uninterrupted for
      a standardized optimum time and intensity of illumination and then terminated by
      addition of a buffer, 'finibuf', which stabilizes the chromophoric complex
      formed. This permits the spectrophotometric absorbance measurements of a number
      of samples collectively and also eliminates the interruption of illumination with
      the concomitant requirement of a spectrophotometer for constant recording of the
      absorbance. This method is of utility to both biochemists and clinicians.

PMID- 11450985
TI  - Hydrogen peroxide, a messenger with too many roles?

PMID- 11450986
TI  - Thyroid hormones, acute iron overload and the pathogenesis of cloudy swelling.

PMID- 11450987
TI  - Signalling apoptosis: a radical approach.
AB  - Reactive oxygen species (ROS) are frequently associated with cytotoxicity, often
      being described as damaging, harmful or toxic. It is generally assumed that,
      under pathological circumstances, ROS elicit wide-spread and random acts of
      oxidation. This passive attack of cellular components by ROS, in conditions where
      oxidative stress is the initiating stimulus for apoptosis, is assumed to simply
      trigger cell death as a result of cumulative oxidative damage. However,
      accumulating evidence now suggests that ROS may act as signalling molecules for
      the initiation and execution of the apoptotic death programme in many, if not
      all, current models of apoptotic cell death. Signalling by ROS would not appear
      to be random, as previously assumed, but targeted at specific metabolic and
      signal transduction cellular components. There is also evidence that the
      enzymatic generation of ROS may not simply be an unwanted by-product of the
      primary reaction catalysed, but that ROS may be used as signalling molecules to
      regulate cellular processes including apoptosis. This view of ROS as signalling
      molecules (as opposed to toxic metabolites) has been further bolstered by the
      findings that cellular antioxidants such as glutathione and thioredoxin not only
      serve to regulate ROS levels but also act as reversible redox modifiers of enzyme
      function. This review will attempt to delineate the involvement of ROS in
      apoptosis in light of these recent discoveries and provide evidence for a crucial
      role for ROS in the initiation and execution of the death process.

PMID- 11450988
TI  - Lysosomal involvement in apoptosis.

PMID- 11450989
TI  - Telomerase activity is not altered by regular strenuous exercise in skeletal
      muscle or by sarcoma in liver of rats.
AB  - Telomerase is a specialized ribonucleoprotein enzyme complex which prevents the
      loss of the telomere. The activity of telomerase can be up- and down-regulated by
      various oxidative stresses but the effect of physical exercise is not known,
      whereas the modifying effect of cancer on telomerase activity is well documented.
      In the first study, we investigated the effect of mild and strenuous exercise
      training on telomerase activity, assessed by a PCR ELISA kit. No alteration in
      telomerase activity was detected. In the second investigation, solid sarcoma
      cells were transplanted to control, exercise trained or exercise trained and
      still exercising mice. On the 16th day after the transplantation, the size of
      tumors in the exercise trained group was 72% and in the exercising group 57% (P <
      0.05) of that in the controls. Telomerase activity and 8-hydroxy-2'
      deoxyguanosine levels in the liver were not significantly altered by exercise
      and/or sarcoma. We conclude that mild and strenuous exercise training does not
      significantly affect the activity of telomerase in the systems studied. Exercise
      training during sarcoma significantly retards the development of tumors and could
      possibly serve as a positive adjunct to treatment.

PMID- 11450990
TI  - Population pharmacokinetic analysis of cisplatin and its metabolites in cancer
      patients: possible misinterpretation of covariates for pharmacokinetic parameters
      calculated from the concentrations of unchanged cisplatin, ultrafiltered platinum
      and total platinum.
AB  - BACKGROUND: Usually, total and filtered platinum concentrations in plasma are
      monitored after cisplatin administration. However, these concentrations represent
      a mixture of unchanged cisplatin and metabolites. In this work, we studied
      population pharmacokinetic analysis based on these platinum concentrations.
      METHODS: Twenty-seven patients (23 males, four females) were administered
      cisplatin (60-100 mg/m2) with intravenous constant infusion for 90 min. Blood
      samples were taken at about three points per patient. The concentrations of
      cisplatin and platinum in the plasma were determined by high-performance liquid
      chromatography and atomic absorption spectrometry, respectively. Population
      pharmacokinetic analysis was performed using the program NONMEM (Version V) with
      the one- or two-compartment model with zero-order infusion. RESULTS: The
      clearance and volume of distribution for all platinum species studied were
      significantly related to the body surface area of the patients. Only the
      clearance of filtered platinum was significantly related to urinary N-acetyl-beta
      D-glucosaminidase and the other covariates were not related to these
      pharmacokinetic parameters with respect to unchanged cisplatin and total platinum
      concentrations. CONCLUSION: The dosage regimen based on the filtered platinum
      concentration which is usually monitored may result in possible misinterpretation
      because the detected covariate is different between unchanged cisplatin and
      filtered platinum.

PMID- 11450991
TI  - Somatic mutation rate of the APC gene.
AB  - BACKGROUND: Somatic inactivation of the wild-type APC gene is involved in the
      development of adenoma of familial adenomatous polyposis. This situation is also
      true in sporadic adenomas. It is of biological interest to know the somatic
      mutation rate of the APC gene. METHODS: The number of stem cells of the colon (N)
      and somatic mutation rate of the APC gene in a stem cell in a year (m) can induce
      age-specific incidence of adenomas. The number of stem cells was estimated as
      10(8) according to previous reports. In the general population, expected adenomas
      at the end of age n years will be approximately Nm2n2/4. In patients with
      polyposis, the expected number of adenomas will be Nmn/2. By setting several
      figures for m, the expected incidence of adenomas was compared with the actual
      occurrences. RESULTS: If the mutation rate was set between 2/10(6) and 3/10(6)
      mutations/stem cell/year, the calculated numbers were well fitted to the actual
      data. Expected adenomas in polyposis patients at the age of 20 and 40 years were
      2000 and 4000 and these were within actual experiences. CONCLUSIONS: This is the
      first study to estimate the somatic mutation rate of the APC gene. The estimated
      somatic mutation rate of the APC gene was between 2/10(6) and 3/10(6)
      mutations/stem cell/year.

PMID- 11450992
TI  - Psychiatric disorders in cancer patients: descriptive analysis of 1721
      psychiatric referrals at two Japanese cancer center hospitals.
AB  - BACKGROUND: Although a diagnosis of cancer today may no longer be considered to
      be the equivalent of a death sentence, many previous studies in Western countries
      have revealed that such a diagnosis places many kinds of emotional burden on a
      patient. However, few studies have focused on the nature of psychiatric disorders
      in Japanese cancer patients. METHODS: We investigated the characteristics, reason
      for psychiatric consultation and psychiatric diagnosis of cancer patients by
      analyzing the database of patients referred to the Psychiatry Divisions at the
      National Cancer Center Hospital and the National Cancer Center Hospital East,
      Japan. RESULTS: Among a total of 1721 referrals, most of the cancer patients
      (78%) were inpatients. Patients with lung cancer (19%) were the most common,
      followed by patients with breast cancer (13%) and with head and neck cancer
      (10%). More than half of the patients had recurrent and/or metastatic cancer and
      60% of the patients had pain. The most common reason for the consultation was
      psychiatric evaluation (35%), followed by sleep disorders (19%), anxiety or fear
      (18%) and depression (18%). Regarding the psychiatric diagnosis, adjustment
      disorders were the most common (34%), followed by delirium (17%) and major
      depression (14%). The diagnosis of cancer had been disclosed to more than 99% of
      the patients. CONCLUSION: The common psychiatric disorders observed in Japanese
      cancer patients were similar to those in the Western countries provided the
      cancer diagnosis is disclosed.

PMID- 11450993
TI  - Influence of postsurgical residual tumor volume on local control in radiotherapy
      for maxillary sinus cancer.
AB  - BACKGROUND: The aim was to study the influence of postsurgical gross residual
      tumor volume on local control of maxillary sinus cancer treated with radiotherapy
      combined with debulking surgery. METHODS: Forty-three patients who underwent
      combined surgery and radiotherapy (50-72 Gy, median 60 Gy) for squamous cell
      carcinoma of the maxillary sinus were reviewed. Gross residual tumor volume
      (GRTV) after surgery was measured on computed tomograms obtained during the
      radiotherapy planning. Patients were classified according to GRTV as follows:
      group AA, GRTV = 0 (microscopic residual, n = 2); group A, GRTV < 10 cm3 (n =
      24); group B, 10-40 cm3 (n = 9); and group C, > or = 40 cm3 (n = 8). The
      relationship between local control and GRTV was analyzed using univariate and
      multivariate analysis. RESULTS: The 2-year local control rate for all patients
      was 62%. The differences in local control rates between groups AA, A and B were
      not significant (P > 0.05), but the rate was significantly lower in group C than
      in the other groups (69% at 2 years vs 31% at 1 year, P < 0.001). Multivariate
      analysis showed that GRTV (P = 0.002) and histological differentiation (poorly
      differentiated histology was favorable, P = 0.035) were independent prognostic
      factors and that intra-arterial chemotherapy and administered total dose were
      not. Local control in groups A and B significantly depended on the total dose of
      radiotherapy, with 2-year control rates of patients receiving 50 Gy (n = 6) and >
      or = 60 Gy (n = 27) of 17% vs 79%, respectively (P < 0.001). CONCLUSIONS: Our
      data suggest that adequate, not complete, debulking associated with a total
      radiotherapy dose of > or = 60 Gy can provide satisfactory local control for
      patients with squamous cell carcinoma of the maxillary sinus.

PMID- 11450994
TI  - Comparison of surgical management of thoracic esophageal carcinoma between two
      referral centers in Japan and China.
AB  - BACKGROUND: Comparison was made between two referral centers, the National Cancer
      Center Hospital (NCCH) in Japan and Shanghai Chest Hospital (SCH) in China. The
      aim was to detect the possible differences between surgical management of
      thoracic esophageal carcinoma in these two countries and to shed some light on
      how to improve the therapeutic outcomes at similar institutions. METHODS: A total
      of 98 patients (50 from NCCH and 48 from SCH) with squamous cell carcinoma of the
      thoracic esophagus treated by a single surgeon at either center during January
      1997 to July 1999 were retrospectively reviewed. RESULTS: Lugol staining and
      endoscopic ultrasonography were applied routinely at NCCH only. More early
      diseases, multiple lesions and synchronous tumors of the digestive tract were
      detected in the NCCH group than in the SCH group. Significantly more stations of
      lymph nodes were dissected and higher metastatic rates to certain stations were
      found after more extensive lymphadenectomy in the NCCH group. Operation time was
      prolonged with significantly more postoperative complication but amount of blood
      loss or in-hospital mortality was not increased. There was a tendency toward
      better survival in the NCCH group at 2-year follow-up (70.9% NCCH vs. 56.2% SCH,
      p = 0.052). CONCLUSIONS: Lugol staining is useful in detecting early diseases or
      multiple lesions and endoscopic ultrasonography in increasing the knowledge of
      preoperative evaluation and thus should be recommended. Attention should be paid
      to more thorough lymph node dissection, especially those lymph node stations with
      high metastatic rates within the chest and the abdomen and meanwhile avoiding
      major postoperative complications, so as to improve further the accuracy of tumor
      staging and therapeutic outcome.

PMID- 11450995
TI  - Pulmonary amyloidosis diagnosed by CT-guided transbronchial biopsy: a case
      report.
AB  - During a medical check-up, a nodular shadow was detected by chest X-ray in the
      right lower lung field of a 59-year-old man. On computed tomography (CT), the
      nodular lesion had a relatively well-defined, irregular margin. A fluoroscopy
      guided bronchoscopic biopsy did not uncover any malignancy. Specimens from a
      subsequent CT-guided bronchoscopic biopsy revealed a pulmonary amyloid deposit.
      As a rule, it is difficult to exclude malignancy or confirm benign disease in
      cases of truly benign lesions, particularly if the lesions are difficult to
      biopsy. Amyloidosis is one of such conditions and requires reliable diagnostic
      methods to avoid unnecessary surgical resection. From our experience, we consider
      CT-guided bronchoscopic biopsy to be a safe and accurate procedure, even when
      applied to truly benign lesions.

PMID- 11450996
TI  - Primary synovial sarcoma of the lung: a case report confirmed by molecular
      detection of SYT-SSX fusion gene transcripts.
AB  - We report a rare case of primary synovial sarcoma of the lung. The patient was a
      49-year-old woman who presented with a well-defined oval-shaped mass in the left
      upper lobe on a chest radiograph. A malignant pulmonary tumor was suspected and
      consequently a left upper lobectomy was performed. Grossly, the tumor measured 5
      x 4 cm, was whitish-yellow in color and soft in consistency. Histologically, the
      tumor showed a dense proliferation of short spindle cells, partly arranged in
      interlacing fascicles. In some areas a hemangiopericytoma-like pattern, stromal
      myxoid change and necrosis of various sizes were noted. Numerous mitotic figures
      were also seen. Immunohistochemically, the tumor cells were positive for
      epithelial markers such as cytokeratin and epithelial membrane antigen. As these
      features suggested a monophasic fibrous type of synovial sarcoma, we examined for
      the presence of SYT-SSXfusion gene transcripts using RNA samples from the frozen
      tumor tissue. A reverse transcription polymerase chain reaction amplified a
      single 583-base pair fragment characteristic of synovial sarcoma. As no other
      tumorous lesions were found during a follow-up period of 1 year, primary synovial
      sarcoma of the lung was our final diagnosis. This tumor should be considered in
      the differential diagnosis of round to short spindle cell tumors arising in the
      lung.

PMID- 11450997
TI  - Complete atrio-ventricular block as a major clinical presentation of the primary
      cardiac lymphoma: a case report.
AB  - It is uncommon for malignant lymphomas to present primarily with cardiac invasion
      as the main clinical feature. What we are interested in is not only where the
      disease is, but also those symptoms that it may induce. Sudden onset of complete
      atrio-ventricular block is one of the most common clinical presentations. Cardiac
      tamponade is another common disease entity which, if it locates over outlets of
      great vessels, may also exert symptoms of obstructive vessels. Diagnosis can be
      made by needle aspiration under the guidance of transcutaneous or transesophageal
      echocardiography. Both CT scan and MRI play positive roles in the diagnosis of
      cardiac lymphomas, and the latter can even provide much more image information
      than the former. We report a 70-year-old male with primary cardiac lymphoma with
      initial clinical pictures of sudden onset of complete atrio-ventricular block.
      Chemotherapy was utilized with cyclophosphamide, vincristine and prednisolone
      (COP) initially for four courses and followed by adding doxorubicin (CHOP) for
      another three courses. The patient was still in remission status after treatment
      for 2 years.

PMID- 11450998
TI  - Colon cancer with meningeal carcinomatosis and myelodysplastic syndrome in a
      patient who underwent intensive chemotherapy for acute myelogenous leukemia: a
      case report.
AB  - A 59-year-old man was admitted to our hospital because of disturbance of
      consciousness and hyponatremia. The patient had suffered from acute myelogenous
      leukemia (AML) with 46,XY and received chemotherapy for 5 years. Meningeal
      carcinomatosis was diagnosed due to the detection of carcinoma cells in the
      cerebrospinal fluid (CSF). Hyponatremia was caused by syndrome of inappropriate
      secretion of anti-diuretic hormone (SIADH). Bone marrow examination revealed
      myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 7.
      Emergence of a new abnormal clone was suggested. The patient died from brain
      herniation. Post mortem examination showed adenocarcinoma in the colon. An
      association between chemotherapy and both colon cancer and MDS was suggested.

PMID- 11450999
TI  - Mucinous adenocarcinoma of Bartholin gland treated with radiation therapy: a case
      report.
AB  - Adenocarcinoma of Bartholin gland is a very rare disease and its molecular
      pathological features are poorly delineated. A 92-year-old woman with mucinous
      adenocarcinoma of Bartholin gland with metastasis to the right inguinal lymph
      node was treated with radiation therapy alone. Despite intensive radiation
      therapy, the tumor was locally recurrent and the patient died 10 months after
      radiation therapy. We searched for the presence of human papillomavirus 16 and 18
      DNA and the expression of p53 protein, CA19-9, CEA and MIB-1 antigen.
      Immunohistochemical study showed that mucinous adenocarcinoma of Bartholin gland
      produced CA19-9 and CEA.

PMID- 11451000
TI  - The urethral sphincter mechanism: where are we now?

PMID- 11451001
TI  - Persistent site-specific defects after reconstructive pelvic surgery.
AB  - Our objective was to determine the persistence rates of site-specific defects
      after reconstructive pelvic surgery. We conducted a retrospective analysis of the
      post-operative outcome for 77 patients with pelvic support defects. Forty-five
      patients in the abdominal group underwent a Burch procedure, paravaginal repair
      and sacral colpopexy when indicated; 32 patients in the vaginal group had a
      sacrospinous vault fixation with or without colporrhaphy. A chi2 test, Wilcoxon's
      two-sample test. Wilcoxon's signed-rank test and multivariate logistic regression
      model were used for data analysis. The two groups were similar in age, weight,
      parity and menopausal status. There was significant improvement of all defects
      except in the vaginal group, which showed a higher rate of persistent paravaginal
      defects (68.7 vs. 13.3%, P = 0.001). After adjusting for potential confounders,
      there was no difference in the rates of apical and anterior wall defects between
      the two groups. The odds ratio for persistent paravaginal defects in the vaginal
      group was 8.9 (95% CI: 2.3-34). The choice of surgical procedure is the most
      important factor determining the rate of persistent pelvic support defects.
      Lateral wall defects must be addressed at the time of reconstructive surgery.

PMID- 11451002
TI  - Changes in the lower urinary tract in continent women and in women with stress
      urinary incontinence, according to menopausal status.
AB  - The aim of this study was to assess the impact of the postmenopausal period on
      clinical and urodynamic parameters and on the mobility of the bladder neck in
      continent women and in women with stress urinary incontinence. Fifty-seven
      postmenopausal women were studied: 30 were continent and 27 had stress urinary
      incontinence. They were subdivided according to postmenopausal stage into groups
      A (<5 years) and B (>5 years). Five years was a good marker to separate those
      women with mild and severe estrogen deficiency. Fifteen premenopausal incontinent
      women were selected for bladder neck ultrasound as controls. All underwent
      history, general physical and gynecologic examinations, LH and FSH
      determinations, type 1 urine and uroculture, circadian voiding diary, cotton-swab
      test, bladder neck ultrasound and urodynamic investigations. Analysis of the
      voiding diaries revealed a higher frequency of daytime micturition in both groups
      of incontinent patients than in the continent ones. Increased bladder neck
      mobility was also found, both in the cotton-swab test and an ultrasound, in group
      A and an ultrasound in the premenopausal incontinent women. Urodynamic
      investigation showed decreased bladder capacity at the first micturition urge, as
      well as decreased urinary volume in the group A patients compared to the
      continent ones. Decreased urethral closure maximum pressure was also found in
      group B patients in relation to the continent ones. We concluded that the effect
      of hypoestrogenism, manifested postmenopause, causes changes in the lower urinary
      tract of women, particularly those who are incontinent.

PMID- 11451003
TI  - Clinical outcome or abdominal urethropexy-colposuspension: a long-term follow-up.
AB  - The aim of this study was to investigate the long-term results of abdominal
      urethropexy-colposuspension in terms of cure rate of stress urinary incontinence,
      complications and side effects. Between 1985 and 1992, 169 women between 27 and
      79 years old underwent abdominal urethropexy-colposuspension at Stockholm Soder
      Hospital. In 1997 they were invited to participate in a long-term follow-up
      study, 5-11 years after the operation. One hundred and thirty-one women (78%)
      were willing to attend for a clinical review; 38 were lost to follow-up. At the
      follow-up visit all women were assessed with medical history, symptoms of
      incontinence, and their satisfaction and problems after the operation, following
      a predefined protocol. Peri- and postoperative data were retrieved from the
      files. The patients underwent a gynecological examination, measurement of
      residual urine volume and a provocative leakage test. One hundred and nine women
      (83%) were satisfied with the results of the operation and 22 (17%) were not.
      Seventy-one (54%) were subjectively completely dry, 48 (35%) had a little leakage
      and 14 (11%) had frequent leakage; 122 women were continent in the provocation
      test, and only 9 (7%) demonstrated leakage. The cure rate for stress incontinence
      was 93%. According to their medical histories 63 (48%) women had mixed
      incontinence before their operation. At the follow-up examination 43 of these 63
      women still had symptoms of urgency. Twenty-six women with genuine stress
      incontinence before the operation had developed urgency or urge incontinence
      during the follow-up period. Urge symptoms before operation was a negative
      prognostic factor for a good outcome in terms of subjective cure of incontinence,
      but had no impact on objective cure rate or satisfaction of the operation. The
      cure rate for stress incontinence was high but still there were women who were
      not satisfied with the operation. Most of these complained of urge incontinence.
      There were few serious complications. The objective cure rate was better than the
      subjective cure rate.

PMID- 11451004
TI  - The use of perineal ultrasound to quantify levator activity and teach pelvic
      floor muscle exercises.
AB  - Perineal ultrasound was used to detect and quantify levator activity by measuring
      the displacement of the internal urethral meatus against the inferoposterior
      margin of the symphysis pubis. Women who had previously been instructed in pelvic
      floor muscle exercises were more likely to contract the levator muscle when asked
      to do so than were those without previous instruction (P<0.0001). Of the 56 women
      who were unable to contract the pelvic floor on request, 32 (57%) eventually
      succeeded with visual ultrasound biofeedback. Pelvic floor muscle assessment and
      teaching can be used as an adjunct to the ultrasound assessment of urogynecologic
      patients, requiring at most 5 minutes. It allows quantification of lavator
      activity and can provide visual biofeedback, which is easily understood and
      readily accepted by women.

PMID- 11451005
TI  - Pharmacological effect of amezinium on urethra and bladder of rabbits.
AB  - The pharmacological effect of amezinium on the urethra and bladder of rabbits was
      investigated. Amezinium produced concentration-dependent contractions in isolated
      urethral strips. The maximum response was approximately 30% of that caused by
      norepinephrine (NE). The concentration-response curve of NE was shifted to the
      left by amezinium. Moreover, amezinium enhanced the relaxative effect of NE on
      carbachol-induced contractions in isolated bladder strips. In anesthetized
      rabbits, amezinium significantly increased the intraurethral pressure (IUP) but
      produced only slight increases in mean blood pressure (MBP). Pre-treatment with
      amezinium ehhanced NE-induced increases in IUP index and MBP. The enhancing
      effect on the IUP index lasted much longer than that on MBP. In a stress
      incontinence model amezinium significantly inhibited the incontinence after an
      i.v. infusion of a low dose of NE. This effect was antagonized by pre-treatment
      with prazosin. These results suggest that amezinium may produce an excellent
      effect for stress incontinence, especially mixed, without severe adverse events
      such as sudden hypertension.

PMID- 11451006
TI  - The standardization of terminology for researchers in female pelvic floor
      disorders.
AB  - The lack of standardized terminology in pelvic floor disorders (pelvic organ
      prolapse, urinary incontinence, and fecal incontinence) is a major obstacle to
      performing and interpreting research. The National Institutes of Health convened
      the Terminology Workshop for Researchers in Female Pelvic Floor Disorders to: (1)
      agree on standard terms for defining conditions and outcomes; (2) make
      recommendations for minimum data collection for research; and (3) identify high
      priority issues for future research. Pelvic organ prolapse was defined by
      physical examination staging using the International Continence Society system.
      Stress urinary incontinence was defined by symptoms and testing; 'cure' was
      defined as no stress incontinence symptoms, negative testing, and no new problems
      due to intervention. Overactive bladder was defined as urinary frequency and
      urgency, with and without urge incontinence. Detrusor instability was defined by
      cystometry. For all urinary symptoms, defining 'improvement' after intervention
      was identified as a high priority. For fecal incontinence, more research is
      needed before recommendations can be made. A standard terminology for research on
      pelvic floor disorders is presented and areas of high priority for future
      research are identified.

PMID- 11451007
TI  - Case-control study of etiologic factors in the development of severe pelvic organ
      prolapse.
AB  - The aim of this case-control study was to identify etiologic factors predictive
      for the development of severe pelvic organ prolapse. Three hundred and sixty
      eight controls from a database describing pelvic organ support in the general
      population were identified as having known good pelvic organ support. Eighty
      seven cases were identified from a urogynecology clinic with severe pelvic organ
      prolapse. The risk of severe prolapse was modeled using stepwise multiple
      logistic regression analysis. Additional analyses using chi2 and two-sample t
      tests were conducted to determine differences in means for individual variables.
      Variables examined included age, gravidity, parity, number of vaginal deliveries,
      weight of largest infant delivered vaginally, menopause status, race, body mass
      index prior to pelvic surgery, and medical illnesses. The following four
      variables were selected in the regression analysis as predicting severe prolapse:
      age, weight of largest vaginal delivery, hysterectomy and previous prolapse
      surgery. Other variables that demonstrated statistically significant differences
      between groups by chi2 and two-sample t-tests were gravidity, parity, number of
      vaginal deliveries, menopausal status, race, history of incontinence surgery and
      the presence of hypertension. Variables that did not demonstrate any significant
      differences were body mass index, the presence of chronic obstructive pulmonous
      disease and diabetes mellitus. Advancing age, increasing weight of infants
      delivered vaginally, a history of hysterectomy and a history of previous prolapse
      surgery were found to be the strongest etiologic predictors of severe pelvic
      organ prolapse in our population.

PMID- 11451008
TI  - Is transabdominal repair of mild to moderate cystocele necessary for correction
      of prolapse during a modified Burch procedure?
AB  - A nonconcurrent cohort study by chart review of cases was carried out at the
      Urogynecology Unit of Mount Sinai Hospital in Toronto, Canada, in 380 patients
      with stress urinary incontinence (SUI) undergoing Burch retropubic urethropexy
      (RPU) with or without transabdominal internal anterior repair (TIAR). There were
      191 subjects (group A) who had both RPU and TIAR, and 189 (group B) who had RPU
      alone. The main outcome measures were postoperative recurrence of cystocele and
      SUI. Statistical analysis was performed using multiple regression analysis;
      P<0.05 was considered statistically significant. Of patients with preoperative
      cystocele grade 1 and 2 (mild to moderate) followed-up at 1 year, recurrence in
      groups A and B, respectively, was found in 13/114 (11.4%) vs. 4/99 (4.0%)
      (P<0.05). Regression analysis showed this trend of greater recurrence with TIAR
      to persist at 5 years, although a significant number of patients were lost to
      follow-up. There was no statistically significant difference in the cure of SUI
      between the groups. There was a 2.1% incidence of inadvertent cystotomy during
      TIAR (with no bladder injuries in group B), although this complication was always
      recognized and repaired without sequelae. In patients with both SUI and mild to
      moderate cystocele, TIAR may not be a necessary addition to RPU for treatment of
      the cystocele, although a randomized clinical trial is needed to determine the
      optimal transabdominal treatment in such cases. There is no detrimental effect of
      TIAR on the Burch procedure's success in curing SUI.

PMID- 11451009
TI  - Mechanism of postoperative urinary continence.
AB  - Stress incontinence used to be attributed mostly to urethral hypermobility, and
      consequently most surgical techniques focused on the region of the bladder neck
      and proximal urethra. This article reviews our knowledge about the mechanism of
      postoperative urinary continence based on anatomic, imaging and urodynamic
      studies. Reduction of urethral mobility, as measured by cotton swab testing or
      imaging studies, is not the only reason why continence surgery succeeds. Imaging
      techniques are of limited value for elucidating the continence mechanism because
      radiologic landmarks and criteria are not reproducible. Urodynamically, the
      increased pressure transmission after successful continence surgery is attributed
      to the retropubic repositioning of the urethra, its compression against the
      anterior vaginal wall, and improved transmission of intra-abdominal pressure
      during stress. The role of the 'functional' urethral obstruction remains to be
      studied. In incontinent patients with hypermobility of the bladder neck and
      proximal urethra continence can be achieved by surgical correction. However,
      stress incontinence is possible in the absence of urethral hypermobility, and
      standard surgical techniques can fail to restore continence in these patients.

PMID- 11451010
TI  - Fistulas of the urinary tract in gynecologic and obstetric surgery.

PMID- 11451011
TI  - Repair of a vaginal evisceration following colpocleisis utilizing an allogenic
      dermal graft.
AB  - Vaginal evisceration following colpocleisis is a very rare event and, to our
      knowledge, there has only been one previous case report. An 86-year-old woman
      presented to the Emergency Department with acute onset of abdominal pain
      occurring following a bowel movement. Six months previously, she had undergone a
      colpocleisis for recurrent vaginal vault prolapse. On presentation to the
      emergency room, she was noted to have 60 cm of necrotic small bowel protruding
      through her vaginal introitus. She was taken to the operating room for resection
      of the small bowel and closure of her colpocleisis. The closure of the vaginal
      defect was difficult and required a vaginal approach employing an allogenic
      dermal graft. This was accomplished and the patient had an uneventful recovery
      and was discharged home. At 18 months followup, she has had no complication or
      recurrence. Evisceration following colpocleisis is a rare event, but can be very
      difficult to manage and we suggest consideration of employing a graft to
      reinforce the repair.

PMID- 11451012
TI  - Pregnancy complicated by a suburethral sling: a case report.
AB  - Incontinence surgery is rarely performed prior to the completion of a woman's
      childbearing. The literature is sparse in regard to women with prior incontinence
      surgery. There are no reports of pregnancy complicated by a sling procedure. A 26
      year-old gravida 3, para 2-0-0-2 with prior surgical history of a Pereyra
      urethropexy followed by a Vesica suburethral sling, was referred at 18 weeks'
      gestation for assessment of the sling. Her antenatal course was complicated by
      pyelonephritis and intermittent urethral obstruction requiring Foley catheter
      placement. She delivered by scheduled cesarean section at 37 weeks' gestation.
      Three months following delivery she presented with pyelonephritis and recurrence
      of her incontinence. Pregnancy complicated by prior suburethral sling procedure
      may result in urinary outlet obstruction, pyelonephritis and disruption of the
      surgical repair.

PMID- 11451013
TI  - The interaction of fresh and frozen-thawed ram spermatozoa with oviducal
      epithelial cells in vitro.
AB  - In order to investigate the interaction of fresh and frozen-thawed spermatozoa
      with oviduct epithelial cells, spermatozoa were co-incubated with ovine oviduct
      epithelial cell monolayers (OECM) derived from either complete oviducts, at any
      stage of the oestrous cycle (Experiments 1 and 2), or from different regions of
      the oviduct at different stages of the cycle (Experiment 3). Fresh and frozen
      thawed spermatozoa displayed different patterns of binding to, and release from,
      the OECM. Frozen-thawed spermatozoa immediately bound to the complete oviduct
      OECM and were released after 2 h. A small proportion of fresh spermatozoa bound
      immediately, increasing to a maximum after 2 h, and were gradually released
      thereafter. When only the cells that were released from the OECM were observed by
      chlortetracycline staining in Experiment 2, it was found that the presence of an
      OECM increased the number of capacitated fresh spermatozoa while decreasing the
      number of capacitated frozen-thawed spermatozoa. Overall, the OECM advanced the
      membrane state of both types of spermatozoa from uncapacitated to acrosome
      reacted. Fresh and frozen-thawed spermatozoa bound to OECM derived from the cells
      of the isthmus and the ampulla in similar proportions. However, more spermatozoa
      were capacitated when incubated with OECM derived from isthmic rather than
      ampullary cells. Higher proportions of fresh spermatozoa bound to, and were
      acrosome-reacted following incubation with OECM derived from post- rather than
      pre-ovulatory tracts. Such differences were not observed for frozen-thawed
      spermatozoa. The findings reported in this study show that fresh and frozen
      thawed spermatozoa behave differently when in contact with oviduct cells in
      vitro. This may be a consequence of the more advanced membrane state of the
      frozen spermatozoa upon thawing.

PMID- 11451014
TI  - Nitric oxide formation from glyceryl trinitrate in the developing guinea-pig
      hippocampus.
AB  - Glyceryl trinitrate (GTN) is classified as an organic nitrate vasodilator drug.
      GTN is considered to be a prodrug because it undergoes biotransformation at its
      site of action to form nitric oxide (NO) or a NO adduct, which produces its
      pharmacologic effect. The objectives of this study were to determine whether the
      hippocampus can biotransform GTN to NO using aerobic conditions, and whether
      biotransformation of GTN to NO is age-dependent during postnatal life. Time
      dependent formation of NO occurred during the incubation of 100 microM GTN with
      2.5% (w/v) homogenate of guinea-pig hippocampus at 37 degrees C using aerobic
      conditions. GTN-derived NO formation was similar in magnitude for the three
      selected postnatal ages that were studied, that is, postnatal days 10, 20 and >
      60. The data demonstrate that the capacity of the hippocampus for NO formation
      from GTN is fully developed in the guinea-pig in early postnatal life. In view of
      these findings, it is conceivable that a NO donor drug, selectively metabolized
      to NO in the hippocampus, could be a useful therapeutic intervention to mitigate
      structural and/or functional defects in this brain region resulting from
      decreased NO formation or availability.

PMID- 11451015
TI  - Changes in susceptibility of bovine sperm to in situ DNA denaturation during
      prolonged incubation at ambient temperature under conditions of exposure to
      reactive oxygen species and nuclease inhibitor.
AB  - Sperm were incubated for up to 9 days in the presence or absence of exogenous
      hydrogen peroxide, phenylalanine, catalase and aurintricarboxylic acid to assess
      the influence of reactive oxygen species and inhibition of deoxyribonucleases on
      sperm chromatin stability. The assessment of sperm DNA susceptibility to in situ
      acid denaturation by the sperm chromatin structure assay did not detect any
      difference in chromatin stability between sperm incubated for 9 days under
      aerobic and anaerobic conditions in a diluent called 14G. Exposure to exogenous
      hydrogen peroxide under both aerobic and anaerobic conditions and to
      phenylalanine under aerobic conditions (which produces hydrogen peroxide by a
      reaction catalysed by the aromatic amino acid oxidase present in sperm) was
      detrimental to sperm chromatin stability, increasing its DNA susceptibility to in
      situ acid denaturation over the incubation time. This effect was eliminated if
      catalase was present in the diluent. Inclusion of the general deoxyribonuclease
      inhibitor aurintricarboxylic acid in the diluent severely decreased sperm
      chromatin stability under both aerobic and anaerobic conditions.
      Aurintricarboxylic acid was mildly cytotoxic, as revealed by viability
      assessment, under aerobic, but not under anaerobic, incubation conditions.
      Exogenous hydrogen peroxide, either directly added to the diluent or generated
      through the enzymatic oxidation of phenylalanine, was detrimental to sperm
      motility and the integrity of the plasma membrane.

PMID- 11451016
TI  - Plasma concentrations of thyroxine and growth hormone in the developing marsupial
      bandicoot, Isoodon macrourus.
AB  - Plasma concentrations of thyroxine (T4) and growth hormone (GH) were measured in
      the developing bandicoot from 21 through to 69 days post partum. Thyroxine
      concentrations increased from 7 ng mL(-1) at 21 days post partum to reach a
      maximum of around 40 ng mL(-1) approximately 40 days post partum. After this
      time, plasma T4 concentrations decreased until about 50 days post partum, when
      levels were not different from those in the adult (9.2 +/- 0.7 ng mL(-1), n =
      10). In contrast, GH concentrations were greatest early in pouch life, with a
      maximum concentration of 88.2 ng mL(-1) at 24 days post partum, and thereafter
      declined to adult levels (4.9 +/- 0.9 ng mL(-1), n = 7) by about 60 days post
      partum. The temporal relationship between T4 and GH in the developing bandicoot
      is similar to that seen in developing eutherian mammals, but in the latter
      species, peak plasma T4 and the decline in GH occur before or soon after
      parturition, whereas in the bandicoot these events occur more than one month post
      partum. This comparison between eutherian mammals and a marsupial indicates that
      the timing of these endocrine changes correlates with key developmental or
      maturational changes rather than the time of parturition.

PMID- 11451017
TI  - Membrane-type matrix metalloproteinase-9 activity in placental tissue from
      patients with pre-existing and gestational diabetes mellitus.
AB  - The activity of matrix metalloproteinase (MMP)-9 was evaluated in placental
      tissue from healthy subjects (controls) and from patients with gestational and
      pre-existing diabetes mellitus (GDM and PDM, respectively). Compared with
      controls, MMP-9 activity was greater in placental tissue from patients with PDM
      and lower in placental tissue from patients with GDM. The modulatory role of
      nitric oxide (NO) and reactive oxygen species (ROS) on MMP-9 activity in
      placental tissue was evaluated. In healthy placenta, NO synthase inhibitors
      diminished MMP-9 activity, whereas NO donors enhanced it. The addition of
      xanthine/xanthine oxidase or hydrogen peroxide to placental incubates enhanced
      MMP-9 activity, while the addition of superoxide dismutase (SOD) diminished it.
      In placental tissue from patients with PDM, MMP-9 activity was stimulated by NO
      and by ROS. In placental tissue from patients with PDM, concentrations of
      nitrates/nitrites and thiobarbituric acid-reactive substances (TBARS) were
      enhanced, whereas SOD activity was decreased, suggesting that elevated
      concentrations of NO and ROS may be related to the enhanced MMP-9 concentrations
      found in these tissues. In placenta from GDM patients, in which a diminished
      concentration of MMP-9 were detected, nitrate/nitrite concentrations were
      increased, but placental MMP-9 activity did not change in the presence of either
      NO donors or inhibitors. The activity of MMP-9 in placental tissue from patients
      with GDM was stimulated by ROS donor systems and was inhibited by the addition of
      SOD; however, TBARS and SOD concentrations were unchanged in these tissues
      compared with controls. These findings demonstrate that placental MMP-9 activity
      is modulated by NO and ROS and that, in diabetic pathology, NO and ROS may
      determine changes in MMP-9 activity, which are probably involved in the
      structural and functional abnormalities of diabetic placental tissue.

PMID- 11451018
TI  - Effects of active and passive gonadotrophin-releasing hormone immunization on
      recognition and establishment of pregnancy in pigs.
AB  - This study investigated the effects of a reduction in gonadotrophins, by means of
      differently timed active and passive gonadotrophin-releasing hormone (GnRH)
      immunization at various stages, on the maintenance of early pregnancy in pigs. In
      the first experiment crossbred sows (n = 11) were immunized against GnRH using a
      commercial vaccine on the day of farrowing, mated at the first oestrus, and a
      booster immunization was administered 10 days (n = 7) or 20 days (n = 4) after
      mating. Plasma samples were collected every second day and assayed for GnRH
      antibodies and progesterone. Pregnancy testing was carried out by real time
      ultrasound. None of the sows receiving the booster immunization 10 days after
      mating were pregnant on Day 18 after mating. All sows receiving the booster on
      Day 20 after mating aborted, with a mean vaccination-to-abortion interval of 10.0
      +/- 1.5 days. In the second experiment, crossbred gilts (n = 6) were passively
      immunized by infusing (i.v.) GnRH immune pig serum on Day 12 after mating.
      Luteinizing hormone profiles were determined on the day before immunization and
      one day afterwards. Daily plasma samples were assayed for GnRH antibodies and
      progesterone. None of the gilts were pregnant 18 days after mating, compared with
      5 of 6 non-immunized controls. Booster immunization 10 days after mating resulted
      in failure of embryonic development and establishment of pregnancy before the
      corpora lutea (CL) regressed, according to progesterone profiles, whereas
      immunization 20 days after mating resulted in regression of CL followed by
      abortion. Passive immunization 12 days after mating had a similar effect to the
      active immunization 10 days after mating. These results demonstrate two different
      outcomes of active GnRH immunization depending on the timing of immunization, and
      indicate that loss of pregnancy between Days 12 and 18 may occur due a reduction
      in progesterone rather than complete failure of the CL, as occurs at later
      stages. The findings may provide an explanation for the reduced fertility of pigs
      in the summer-autumn period.

PMID- 11451019
TI  - Localization of endothelial nitric oxide synthase messenger ribonucleic acid by
      in situ hybridization in ectopic endometrial tissue in patients with adenomyosis.
AB  - This study was undertaken to determine the expression of endothelial nitric oxide
      synthase (NOS) mRNA in ectopic endometrium in adenomyosis. Endothelial NOS mRNA
      expression was investigated by in situ hybridization using a human endothelial
      NOS RNA probe. The subjects comprised six cases of adenomyosis, and 14 women with
      normal fecundity as controls. Specific expression of endothelial NOS mRNA was
      found in glandular and surface epithelial cells in eutopic endometrium throughout
      the menstrual cycle in all groups. It is noteworthy that the expression of
      endothelial NOS mRNA was moderately positive in ectopic endometrial tissues in
      three of the six cases of adenomyosis. In conclusion, the endothelial NOS mRNA
      expression seen in the ectopic endometrium suggests a possible relationship with
      the various pathologies associated with adenomyosis.

PMID- 11451020
TI  - Lipid hydroperoxide and cGMP are not involved in nitric oxide inhibition of
      steroidogenesis in bovine granulosa cells.
AB  - The present study was performed to explore two of the possible signalling
      mechanisms through which nitric oxide (NO) inhibits steroidogenesis in bovine
      granulosa cells. Because cGMP is generally known to play a pivotal role in NO
      signal transduction, the first aim of the present study was to verify the
      presence of a functional NO-cGMP signalling pathway. Because non-cGMP-dependent
      pathways could be involved in the inhibition of steroidogenesis by NO, we
      examined the formation of lipid hydroperoxides (LPOs), possibly induced by NO.
      Using bovine granulosa cells collected from small (< 5 mm) and large (> 8 mm)
      follicles, the effectiveness of the NO donor s-nitroso-N-acetylpenicillamine
      (SNAP; 10(-3), 10(-4) and 10(-5) M) in stimulating cGMP production and the
      formation of LPOs was examined. The second aim of the present study was to
      determine whether the effects of NO on steroidogenesis could be mimicked by
      treatment of cells with a cGMP analogue (8-bromo-cGMP (8-Br-cGMP); 10(-3), 10(-4)
      and 10(-5) M) and whether these effects could be reversed by [1H]
      [1,2,3]oxadiaziolo[4,3a]quinoxaline-1-one (ODQ; 10(-5) and 10(-4) M) an inhibitor
      of NO-sensitive soluble guanylate cyclase. The highest dose of SNAP used induced
      a significant (P<0.01) increase in cGMP levels, while other concentrations tested
      were ineffective. Neither concentration of ODQ used significantly inhibited basal
      cGMP output, while both concentrations counteracted the stimulatory effect of
      SNAP. Treatment of cells with 8-Br-cGMP and ODQ was ineffective in modifying
      steroidogenesis. Treatment with SNAP, at the three concentrations tested, had no
      significant effect on the level of LPOs. The present results suggest that NO
      inhibits steroidogenesis in bovine granulosa cells without involving cGMP and
      LPOs.

PMID- 11451021
TI  - Heterogeneous osmotic behaviour in boar sperm populations and its relevance for
      detection of changes in plasma membrane.
AB  - The spermatozoa of most mammals behave as 'perfect osmometers'. The volume
      response to osmolality obeys the Boyle-Van't Hoff relationship (i.e. volume
      changes are determined by the osmotically active fraction of the cell volume
      (solids and water)). Most evaluations of osmotic sperm cell behaviour have been
      based on the mean volume of the cell population. In the present study, both mean
      and modal volumes of samples of sperm were evaluated. Both mean and modal volumes
      responded to environmental osmolality via the Boyle-Van't Hoff relationship;
      however, the modal volume showed a more sensitive response than the mean volume.
      This was confirmed for both ejaculated and epididymal spermatozoa. After
      incubation under capacitating conditions, the difference in modal and mean volume
      response of ejaculated sperm was considerably diminished and, in epididymal
      sperm, completely abolished. The sperm osmotic behaviour was still consistent
      with the Boyle-Van't Hoff equation, but the apparent osmotically inactive modal
      cell volume decreased after exposure to capacitating conditions in both
      ejaculated and epididymal sperm samples. The changes in epididymal sperm were
      more intensive. Due to its enhanced sensitivity to environmental osmolality and
      incubation under capacitating conditions, the modal volume could be used as a
      parameter for evaluating sperm population response, such as for detecting
      environmentally or cryopreservation-induced membrane changes.

PMID- 11451022
TI  - Role of cyclic adenosine 3',5'-monophosphate and serum albumin in head-to-head
      agglutination of boar spermatozoa.
AB  - It has previously been shown that when boar spermatozoa are incubated in a
      modified Krebs-Ringer bicarbonate (mKRB), head-to-head agglutination occurs in
      many cells. The aim of the present study was to investigate the effects of cyclic
      adenosine 3',5'-monophosphate (cAMP) and serum albumin on sperm agglutination and
      to discuss a possible mechanism for sperm agglutination. Spermatozoa were
      collected from four mature boars, washed and incubated in mKRB. After a 1-h
      incubation, a sample of each sperm suspension was smeared gently on a separate
      glass slide, dried and stained in a phosphate-buffered solution of Giemsa to
      assess the percentage of head-to-head agglutinated cells in each suspension. In
      the samples incubated in mKRB, approximately 50% of the spermatozoa were
      agglutinated with one another at the acrosome. However, the percentages of head
      to-head agglutinated spermatozoa were greatly reduced by a lack of calcium
      chloride in mKRB, but were recovered by the addition of dibutyryl cAMP (dbcAMP, a
      cAMP analogue) in a dose-dependent manner between 1 and 1000 microM. Addition of
      3-isobutyl-1-methylxanthine (IBMX, 100 and 500 microM) instead of dbcAMP also
      significantly increased the percentages of head-to-head agglutinated spermatozoa.
      Moreover, the effects of adding dbcAMP were attenuated by treatment with Rp
      adenosine 3',5'-cyclic monophosphorothioate triethylamine salt (0.25-1.0 mM, a
      cAMP antagonist) or H-89 (5 microM, a protein kinase-A inhibitor), but were
      enhanced by treatment with okadaic acid (500 nM) and calyculinA (500 nM)
      (inhibitors of protein serine/threonine phosphatase). In sperm samples incubated
      in mKRB containing 0.1% polyvinyl alcohol (mKRB-P) or mKRB-P lacking calcium
      chloride and supplemented with 1 mM dbcAMP, a lack of bovine serum albumin (BSA)
      resulted in a significant decrease in the percentages of head-to-head
      agglutinated spermatozoa. Addition of porcine serum albumin (PSA, 1-4 mg mL(-1))
      or methyl-beta-cyclodextrin (MBC, 5-10 mg mL(-1)) instead of BSA was as effective
      as BSA (4 mg mL(-1)) in enhancing sperm agglutination. However, the effects of
      BSA (4 mg mL(-1)) or MBC (5 mg mL(-1)) were reduced by pre-mixing these reagents
      with cholesterol 3-sulfate (a cholesterol analogue, 5 microg mL(-1) for BSA and
      375 microg mL(-1) for MBC). In addition, a protein 'anti-agglutinin' inhibiting
      sperm agglutination, was extracted from spermatozoa incubated with serum albumin
      or MBC and detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      and Western blotting techniques. The obtained Western blots revealed that sperm
      bound anti-agglutinin was detected less in the samples incubated with either BSA
      (4 mg mL(-1)) or MBC (5-10 mg mL(-1)), compared with control samples. Moreover,
      pre-mixing MBC (5 mg mL(-1)) with cholesterol 3-sulfate (375 microg mL(-1))
      reduced this reagent's effects on the loss of sperm-bound anti-agglutinin.
      Additionally, the assay of sperm agglutination and a chlortetracycline staining
      assay revealed that the percentages of head-to-head agglutinated spermatozoa were
      positively correlated with those of spermatozoa classified into B pattern
      (capacitated spermatozoa). These results are consistent with the following
      suggestions: (i) an adenylyl cyclase-cAMP-protein kinase system mediates a
      signalling pathway leading to head-to-head agglutination; and (ii) loss of anti
      agglutinin from the spermatozoa may be modulated by changes in the plasma
      membrane induced by actions of serum albumin or MBC contained in a medium.

PMID- 11451023
TI  - Muscle growth, cell number, type and morphometry in single and twin fetal lambs
      during mid to late gestation.
AB  - Muscle growth, myofibre number, type and morphometry were studied in large
      hindlimb muscles of single and twin fetal lambs during mid to late gestation.
      Placental insufficiency, evident by lower total placentome weight and number per
      fetus, resulted in reduced fetal weights from 100 to 140 days gestation in twins
      compared with singletons (at 140 days: 5016 +/- 108 g v. 5750 +/- 246 g,
      respectively; P<0.05). However, competition between littermates did not
      consistently reduce muscle mass (15-22%) until 140 days gestation. Apparent
      myofibre number increased with age, indicating that the full complement of
      myofibres in some large hindlimb muscles may be achieved during early postnatal
      life. Litter size did not impact on apparent myofibre number in the
      semitendinosus, plantaris or gastrocnemius muscles. However, a transient effect
      on myofibre number in the adductor femoris muscle was observed from 80-120 days
      gestation. The phenotypic maturation of myofibres was unaffected by increasing
      litter size. Smaller muscle mass in twins was associated with smaller myofibre
      cross-sectional area in the semitendinosus, adductor femoris and gastrocnemius
      muscles at 140 days gestation. A similar trend was observed for the plantaris
      muscle. These results indicate that while competition between littermates for
      nutrients in late gestation can impact on both fetal and muscle mass, the fetus
      has the capacity to buffer against the effects of restricted nutrient supply on
      myofibre hyperplasia and phenotypic maturation, but myofibre hypertrophy is
      compromised.

PMID- 11451024
TI  - Morphometric analysis of myofibre development in the adductor femoris muscle of
      single and twin fetal lambs.
AB  - Cellular development of the adductor femoris muscle from twin and single fetuses
      was studied at 140 days gestation to evaluate the effect of moderate fetal growth
      retardation on myofibre development. Twin fetuses had lower bodyweights (13%) and
      disproportionately small adductor femoris muscle weights (22%) compared with
      single fetuses. Reduced muscle mass was associated with smaller myofibre cross
      sectional areas (CSA) and lower DNA content (22%), indicative of fewer myonuclei
      and retarded myofibre hypertrophy. Myofibre number and the phenotypic maturation
      of the myofibres were similar between twins and singletons. These results
      indicate that even modest growth restriction during fetal life can negatively
      influence myofibre hypertrophy, highlighting the importance of fetal nutrition
      for muscle growth. Large muscles, such as the adductor femoris, have
      intrafascicularly terminating myofibres, which necessitates accurate sampling of
      the muscle when investigating possible perturbations in morphological
      characteristics (e.g. between singletons and twins). The second objective of the
      present study was to investigate the impact of the sampling site on the
      morphological parameters of the adductor femoris muscle. The apparent total
      myofibre number decreased from the proximal to the distal region of the adductor
      femoris muscle. The apparent number of slow-twitch fibres also decreased from the
      proximal to the medial region, but was not different between the medial and
      distal regions of the muscle. Similarly, myofibre CSA differed between the medial
      and distal regions. These results indicate that, particularly with large muscles,
      such as the adductor femoris, which has intrafascicularly terminating myofibres,
      single site sampling for the determination of morphological fibre characteristics
      may generate misleading results and that careful selection of the sampling area
      may be necessary.

PMID- 11451025
TI  - Sperm viability and morphology of two genetically diverse Merino lines.
AB  - Microscopically evaluated sperm parameters, as well as computer-aided sperm
      motility analysis (CASMA), were used to assess sperm quality and the effect of
      cryopreservation on ram semen obtained from two genetically diverse Merino lines.
      These lines were divergently selected on maternal ranking values for multiple
      rearing ability from the same base population since 1986. Replacements in the
      high (+) line were preferentially the progeny of ewes rearing >1 lamb per
      joining. Progeny of ewes rearing <1 lamb per joining was preferred as
      replacements in the low (-) line. Sperm quality, as assessed by percentages of
      live, abnormal and acrosome-intact spermatozoa as well as by motility, was
      independent (P < or = 0.20) of line, time of sampling and their interaction in
      ejaculated samples obtained from the eight rams used as sires in 1995. Sperm
      quality of frozen-thawed samples was adversely affected (P < or = 0.01) by
      cryopreservation and thawing at 35 degrees C for 30 s relative to fresh
      ejaculated samples. No consistent differences between lines were found in
      epididymal sperm samples obtained from 12 slaughtered rams (6 from each line).
      The adverse effect (P < or = 0.05) of cryopreservation and thawing at 35 degrees
      C for 30 s on sperm viability and motility was also demonstrated for these
      samples.

PMID- 11451026
TI  - Nonlinear dynamics and chaos theory: concepts and applications relevant to
      pharmacodynamics.
AB  - The theory of nonlinear dynamical systems (chaos theory), which deals with
      deterministic systems that exhibit a complicated, apparently random-looking
      behavior, has formed an interdisciplinary area of research and has affected
      almost every field of science in the last 20 years. Life sciences are one of the
      most applicable areas for the ideas of chaos because of the complexity of
      biological systems. It is widely appreciated that chaotic behavior dominates
      physiological systems. This is suggested by experimental studies and has also
      been encouraged by very successful modeling. Pharmacodynamics are very tightly
      associated with complex physiological processes, and the implications of this
      relation demand that the new approach of nonlinear dynamics should be adopted in
      greater extent in pharmacodynamic studies. This is necessary not only for the
      sake of more detailed study, but mainly because nonlinear dynamics suggest a
      whole new rationale, fundamentally different from the classic approach. In this
      work the basic principles of dynamical systems are presented and applications of
      nonlinear dynamics in topics relevant to drug research and especially to
      pharmacodynamics are reviewed. Special attention is focused on three major fields
      of physiological systems with great importance in pharmacotherapy, namely
      cardiovascular, central nervous, and endocrine systems, where tools and concepts
      from nonlinear dynamics have been applied.

PMID- 11451027
TI  - Water-soluble and low molecular weight chitosan-based plasmid DNA delivery.
AB  - PURPOSE: Chitosan, a natural cationic polysaccharide, is a candidate non-viral
      vector for gene delivery because of its high positive charges and low
      cytotoxicity. In this study, low molecular weight chitosan (LMWC, molecular
      weight of 22 kDa) was characterized and evaluated as a gene carrier. METHODS:
      Plasmid/LMWC complex was analyzed in 1% agarose gel electrophoresis. To confirm
      that the LMWC protected plasmids from nuclease. DNase I protection assays were
      performed. pSV-beta-galactosidase plasmid/LMWC complex was transfected into 293T
      cells and transfection efficiency was evaluated by beta-galactosidase assay.
      Cytotoxicity of LMWC was determined by MTT assay. RESULTS: Unlike high molecular
      weight chitosan (HMWC), LMWC is highly water soluble, and can form complex with
      plasmids in physiological buffer. The plasmid DNA was completely retarded at a
      weight ratio of 1:2 (plasmid:LMWC) in 1% agarose gel. DNase I protection assay
      showed that plasmids were protected from DNase-I over 60 min. The most efficient
      transfection was obtained at a weight ratio of 1:3 (plasmid:LMWC). The
      transfection efficiency of LMWC was significantly higher than naked DNA and
      higher than poly-L-lysine (PLL). MTT assay showed that LMWC was less cytotoxic
      than PLL. CONCLUSIONS: LMWC is non-toxic and has higher transfection efficiency
      than PLL. Therefore, LMWC will be useful in the development of safe gene
      carriers.

PMID- 11451028
TI  - Inhibition of P-glycoprotein transport function by grapefruit juice psoralen.
AB  - PURPOSE: The grapefruit juice component bergamottin is known to inactivate
      cytochrome P450 3A4, with grapefruit juice consumption causing increased
      absorption and enhanced oral bioavailability of many cytochrome P450 3A4
      substrates. Many of these substrates are also recognized by the efflux
      transporter P-glycoprotein. The gene product of MDR1 (multidrug resistance
      transporter), P-glycoprotein also confers protection against xenobiotics.
      METHODS: Using a whole ceil assay in which the retention of a marker substrate is
      evaluated and quantified, we studied the ability of grapefruit juice components
      to inhibit the function of this transporter. RESULTS: In a cell line presenting
      an overexpressed amount of the human transporter, the enzyme exhibited a 40
      microM IC50 for inhibition by bergamottin. Additionally, using the ATP-hydrolysis
      assay, we showed that bergamottin increases P-gp-mediated ATP hydrolysis by
      approximately 2.3 fold with a Km of 8 microM. The concentration for this
      interaction is similar to that for CYP3A4 inactivation. CONCLUSIONS: These
      results suggest that observed grapefruit juice drug pharmacokinetic clinical
      interactions may be due to P-gp inhibition rather than or in addition to CYP3A4
      inhibition. Inhibition of P-gp by citrus psoralens could present ways both to
      enhance bioavailability of therapies without increasing the dose and to diminish
      drug resistance in refractory cells.

PMID- 11451029
TI  - Up-regulation of carnitine transporters helps maintain tissue carnitine levels in
      carnitine deficiency induced by pivalic acid.
AB  - PURPOSE: Pivalic acid (PVA) forms conjugates with endogenous carnitine and
      enhances its excretion. The purpose of this study is to determine whether tissue
      carnitine levels decrease in parallel with plasma levels in carnitine deficiency
      induced by PVA. METHODS: PVA was orally administered to rats for 5 days.
      Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The
      tissue uptake clearance (CLuptake) was determined in vivo by the integration plot
      method. Hepatocytes were prepared from control and PVA-treated rats, and the
      uptake of L-carnitine was determined. RESULTS: Plasma concentrations of L
      carnitine decreased as a result of the enhanced carnitine elimination as
      pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine
      concentrations in liver, muscle, and heart remained relatively constant during
      the study. period. CLuptake increased in liver and muscle and, thus, the rate of
      carnitine uptake from plasma into these tissues did not change even at low plasma
      concentrations. This helps maintain carnitine levels in these tissues. Up
      regulation of carnitine transporters is suggested to be a mechanism for the
      increased CLuptake. CONCLUSIONS: In the carnitine deficiency state induced by
      PVA, increased CLuptake owing to up-regulation of carnitine transporters is
      suggested to help maintain carnitine levels in some tissues.

PMID- 11451030
TI  - Improving the selectivity of HAV-peptides in modulating E-cadherin-E-cadherin
      interactions in the intercellular junction of MDCK cell monolayers.
AB  - PURPOSE: The objective of this work is to understand the sequence specificity of
      HAV peptides and to improve their selectivity in regulating E-cadherin-E-cadherin
      interactions in the intercellular junctions. METHODS: Peptide 1 was modified
      using an alanine scanning method to give peptides 2-6. The ability of these
      peptides to modulate intercellular junctions was evaluated using Madin-Darby
      Canine Kidney (MDCK) cell monolayers on Transwell membranes from either the
      apical (AP) or the basolateral (BL) side. Modulation of the intercellular
      junctions was measured by the ability to lower the transepithelial electrical
      resistance (TEER) of MDCK monolayers and by the increase in mannitol flux.
      Molecular docking experiments were performed to model the binding properties of
      these peptides to the EC1 domain of E-cadherin. RESULTS: Peptides 5 (Ac-SHAVAS
      NH2) and 6 (Ac-SHAVSA-NH2) were found to be more effective than the parent
      peptide 1 in decreasing the resistance of the cell monolayer. Furthermore,
      comparative studies with the control and the weak inhibitor peptide 2 indicate
      that peptide 5 displayed a significant increase in mannitol flux. Molecular
      docking of peptides 1, 2 and 5 to the EC1 domain suggests that peptide 5 has the
      lowest binding energy. CONCLUSIONS: HAV peptides have the ability to modulate E
      cadherin-E-cadherin interactions in the intercellular junctions of the MDCK cell
      monolayer, thus indirectly increasing the permeability of the tight junctions.
      This observation indicates that residues flanking the HAV sequence are important
      in the binding selectivity of HAV peptides to E-cadherin. Molecular docking can
      further aid in the design of peptides with better selectivity to the EC1 domain
      of E-cadherin.

PMID- 11451031
TI  - Once-a-day oral dosing regimen of cyclosporin A: combined therapy of cyclosporin
      A premicroemulsion concentrates and enteric coated solid-state premicroemulsion
      concentrates.
AB  - PURPOSE: To develop once-a-day oral dosing regimen that provides the blood levels
      of cyclosporin A (CsA) in the therapeutic ranges over 24 hours. METHODS: CsA
      premicroemulsion concentrates (preME) were formulated from phase diagrams.
      Enteric-coated solid-state premicroemulsion concentrates (sME) were prepared by
      coating preME with enteric-coating matrials and solidifying them. CsA was
      measured using high-performance liquid chromatography or radioimmunoassay.
      RESULTS: PreME consisted of CsA, oil, and mixture of surfactants and a
      cosurfactant. PreME spontaneously formed microemulsions in aqueous medium and
      showed oral absorption profiles similar to Sandimmune Neoral in dogs. Dispersion
      of sME in aqueous medium also formed microemulsions. Release rates of CsA from
      sME depended on pH and the type of enteric-coating materials and highly
      correlated with the extent of oral absorption. The co-administration of preME and
      sME (200 mg CsA) showed the maximum blood level of CsA not significantly
      different from that of preME (100 mg CsA) and the concentration of CsA close to
      the minimum therapeutic level at 24 hours. CONCLUSIONS: The combined treatment of
      preME and sME provided controlled oral absorption of CsA over a 24-hour period.
      Such once-a-day dosing regimens will lead to increased patient compliance and
      reduced episodes of organ rejection after transplantation.

PMID- 11451032
TI  - Monitoring the intragastric distribution of a colloidal drug carrier model by
      magnetic resonance imaging460.
AB  - PURPOSE: Monitoring the distribution of drugs or drug delivery systems in the
      human gastrointestinal tract is an important prerequisite for the design of
      orally administered drugs. We investigated the intragastric distribution of a
      colloidal drug delivery system (liposomes containing the contrast agent Gd-DOTA)
      by magnetic resonance imaging. METHODS: Following ingestion of a liquid or a
      solid meal, gastric distribution of liposomes released from a capsule and the fat
      component of the solid meal were tracked in 7 healthy subjects for 90 min.
      Liposomes were identified in gastric content by the increased signal intensity
      provided by the encapsulated Gd-DOTA. RESULTS: With the liquid meal, liposomes
      initially formed a layer on the surface before distributing in 86 +/- 2% of
      gastric content (maximum distribution volume) within 42 +/- 6 min. With the solid
      meal, maximum distribution (7 +/- 1%, reached within 24 +/- 6 min) was confined
      to a small volume in the fundus without forming a layer, suggesting that
      distribution was related to the accessible liquid compartment. Fat distribution
      was inhomogeneous and concentrated in the fundus. CONCLUSIONS: Intragastric
      distribution of a colloidal drug carrier model, such as Gd-DOTA-filled liposomes,
      varies between meals of different composition. These differences can be monitored
      in three dimensions in humans by MRI.

PMID- 11451033
TI  - Targeting of 3'-azido 3'-deoxythymidine (AZT)-loaded poly(isohexylcyanoacrylate)
      nanospheres to the gastrointestinal mucosa and associated lymphoid tissues.
AB  - PURPOSE: The aim of the studv was to evaluate the capacity of
      poly(isohexylcyanoacrylate) nanospheres to concentrate 3'-azido 3'-deoxythymidine
      (AZT) in the intestinal epithelium and associated immunocompetent cells, which
      are known to be one of the major reservoirs of the human immunodeficiency virus
      (HIV). METHODS: The tissue concentration of 3H-radiolabeled AZT in the
      gastrointestinal (GI) tract was obtained 30 and 9() minutes after intragastric
      administration to rats at a dose of 0.25 mg AZT/100 g of body weight. The
      distribution along the intestine was determined. AZT concentrations in the lymph
      were obtained by lymphatic duct cannulation. RESULTS: Unlike the solution.
      nanoparticles did concentrate AZT very cfficiently in the intestinal mucosa, as
      well as in the Peyer's patches, and could simultaneously control the release of
      free AZT. Concentration in Peyer's patches was 4 times higher for nanoparticles,
      compared with the control solution. The tissue concentration was 30-45 microM,
      which was much higher than the reported IC50 of AZT (0.06-1.36 microM) and was
      regularly distributed along the gastrointestinal tract. CONCLUSIONS:
      Nanoparticles have been shown to be efficient in concentrating AZT in the
      intestinal epithelium and gut-associated lymphoid tissues, supporting the view
      that these particles may represent a promising carrier to treat specifically the
      GI reservoir of HIV.

PMID- 11451034
TI  - Effect of sucrose/raffinose mass ratios on the stability of co-lyophilized
      protein during storage above the Tg.
AB  - PURPOSE: To examine the potential of raffinose as an excipient in stabilizing
      protein and to study the effect of sucrose/raffinose mass ratios on the stability
      of co-lyophilized protein and amorphous solids during storage at an elevated
      temperature. METHODS: Glucose-6-phosphate dehydrogenase (G6PDH) was colyophilized
      with sucrose and raffinose mixed at different mass ratios. The activity of dried
      G6PDH was monitored during storage at 44 degrees C. Thermal properties of
      sucrose/raffinose matrices were determined by differential scanning calorimetry
      (DSC). RESULTS: Mass ratios of sucrose to raffinose did not affect the recovery
      of G6PDH activity after freeze-drying, but significantly affected the stability
      of freeze-dried G6PDH during storage. The sucrose-alone formulation offered the
      best enzyme stabilization during storage. With increasing fraction of raffinose,
      the G6PDH stability decreased, sugar crystallization inhibited, and crystal
      melting temperature increased. CONCLUSIONS: Despite the higher Tg of the
      formulations with higher fraction of raffinose, they provided less protection for
      G6PDH than did sucrose alone during storage. Our data do not support the
      prediction from recent thermophysical studies that raffinose should be superior
      to sucrose and trehalose as a potential excipient or stabilizer.

PMID- 11451035
TI  - A study of the effects of the physical characteristics of microcrystalline
      cellulose on performance in extrusion spheronization.
AB  - PURPOSE: Physical characterization and extrusion-spheronization profiles of 11
      microcrystalline cellulose (MCC) grades were performed. Correlation between the
      physical characteristics and extrusion spheronization behavior and pellet quality
      was performed to determine critical MCC characteristics that influence the water
      requirement and spheronization water sensitivity for extrusion-spheronization.
      METHODS: Extrusion spheronization of MCC-lactose at varying water contents was
      performed to determine water requirement, spheronization water sensitivity, and
      the effect of increasing water content on some pellet qualities (pellet flow
      rate, friability, bulk, and tapped densities) of each MCC grade. MCC physical
      properties and tapping characteristics were assessed. Correlation between MCC
      physical properties and its spheronization behavior parameters was performed.
      RESULTS: MCC characteristics, such as powder particle size, size distribution,
      and porosity, were found to have little influence on the extrusion-spheronization
      process. However, significant correlation was found between void volumes or
      packing properties of MCC and the water requirement for extrusion-spheronization
      and pellet qualities. CONCLUSIONS: A new insight into the action of MCC as a
      spheronizing aid was discovered. MCC void volume and packing properties play an
      important role in determining water retention and release during extrusion
      spheronization.

PMID- 11451036
TI  - A quantitative assay of telomerase activity.
AB  - PURPOSE: Telomerase is a ribonucleoprotein that extends telomeres at the ends of
      chromosome. Increased telomerase activity is associated with cellular
      immortality. The currently available assay for telomerase, i.e., telomeric repeat
      amplification protocol (TRAP), consists of 2 steps: (a) telomerase-mediated
      extension of an oligonucleotide primer by the enzyme-containing extracts of cells
      and tissues, and (b) amplification of the telomerase-extended primer products by
      polymerase chain reaction (PCR) and detection of the PCR products. It is
      generally accepted that the current TRAP assay lacks quantitative precision. The
      present study was to develop a quantitative telomerase assay with greater
      precision and sensitivity. METHODS: This new method used the primer extension
      method as in TRAP, plus the following modifications: (a) used a lysis buffer that
      yielded complete lysis of nuclei; (b) removal of PCR inhibitors by
      phenol/chloroform extraction after primer extension; and (c) used primers for the
      internal standard that were designed to reduce their competition with the
      telomerase products for PCR. RESULTS: The modified method showed a good
      correlation (r2 = 0.99, P < 0.001) between telomerase amount (expressed as total
      protein in cell lysate) and its activity (expressed as telomerase products).
      Compared to the conventional TRAP, the new method (a) was more sensitive (average
      of 5.5-fold in cultured cancer cells and >5.9-fold in patient tumors), (b) had a
      lower inter- and intra-day variability (>3fold), and (c) showed a 2 to 4-fold
      broader range of linearity in the standard curve. The higher assay sensitivity
      further enabled the use of a nonradioactive method, i.e., ethidium bromide
      staining of DNA, to detect the TRAP products, as opposed to the use of
      radioactive nucleotide and the more labor-intensive autoradiography mandated by
      the conventional TRAP. CONCLUSION: We report here a quantitative assay for
      telomerase activity in cultured human cancer cells and patient tumors.

PMID- 11451037
TI  - Effects of topical anandamide-transport inhibitors, AM404 and olvanil, on
      intraocular pressure in normotensive rabbits.
AB  - PURPOSE: To evaluate the effects of topically applied anandamide transport
      inhibitors, AM404 and olvanil, on the intraocular pressure (IOP) of normotensive
      rabbits. To determine if the ocular hypotension induced by topical anandamide
      (AEA) can be potentiated by co-administered AM404. METHODS: Test compounds, in
      either hydroxypropyl-beta-cyclodextrin (HP-beta-CD) or propylene glycol, were
      administered unilaterally onto rabbit eyes. To determine if AM404 affects the IOP
      profile of AEA, AM404 was administered ocularly 15 minutes before topical AEA.
      Phenylmethylsulfonyl fluoride (PMSF) (24 mg/kg, s.c.) was given 30 min before AEA
      to prevent its catabolism. IOPs of the treated and untreated eyes were measured.
      The cannabinoid agonist activities of AM404 and olvanil were studied by using
      [35S]GTPyS autoradiography. RESULTS: Topical AM404 (62.5 micirog), in HP-beta-CD
      vehicle, decreased IOP significantly in treated eyes. AM404 (62.5 microg) induced
      a significant IOP increase without subsequent decrease when given in propylene
      glycol vehicle. Olvanil (312.5 microg) caused a significant IOP reduction without
      provoking an initial hypertensive phase. These compounds did not significantly
      affect the IOP of untreated eyes. Co-administered AM404 (125 microg in HP-beta
      CD) had no significant effect on the IOP profile of AEA (62.5 microg).
      CONCLUSIONS: Ocular administration of AM404 or olvanil decreased IOP in rabbits,
      although AM404 can provoke an initial ocular hypertension and did not potentiate
      the IOP responses induced by exogenous AEA.

PMID- 11451038
TI  - Assessment of tear concentrations on therapeutic drug monitoring. II.
      Pharmacokinetic analysis of valproic acid in guinea pig serum, cerebrospinal
      fluid, and tears.
AB  - PURPOSE: To quantitatively describe the pharmacokinetics of valproic acid (VPA)
      in guinea pig serum (total [Cf+b] and free [Cf]), cerebrospinal fluid (CSF)
      [C]CSF and tears [C]T using a simple kinetic model, and to examine whether [Cf]
      and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic
      parameters. METHODS: [Cf+b], [Cf], [C]CSF and [C]T were determined after bolus
      i.v. injection of 10 or 20 mg/kg VPA using GC/ECNCI/MS. RESULTS: [Cf+b] could be
      quantitatively described by a two compartment model with linear elimination
      kinetics. [Cf] was separately analyzed using multi-exponential equations. [C]CSF
      was analyzed using a simple kinetic model in which the CSF compartment is
      independently connected with the serum compartment by the apparent diffusion
      constants (KINCSF and KOUTCSF). [C]T was analyzed using the same simple kinetic
      model used for [C]CSF. The values of [C]CSF and [Cf] in the steady state can be
      represented by the following equations; [C]CSF = KINCSF/KOUTCSF x [Cf], [Cf] =
      KOUT/KINT x [C]T, and indicating that [Cf] and [C]CSF can be predicted by [C]T
      using the resulting pharmacokinetic parameters. CONCLUSIONS: The measurement of
      [C]T which can be collected non-invasively and estimated the pharmacokinetic
      parameters for [Cf], [C]CSF, and [C]T might be a very useful method for TDM of
      VPA.

PMID- 11451039
TI  - Rat and rabbit plasma distribution of free and chylomicron-associated BIRT 377, a
      novel small molecule antagonist of LFA-1-mediated cell adhesion.
AB  - PURPOSE: The objectives of this study are to determine the plasma distribution of
      free and chylomicron-associated BIRT 377 within rats and rabbits. METHODS: For
      the rat studies free and chylomicron-associated BIRT 377 was incubated in plasma
      from CD 1 non-fasted rats for 60 minutes at 37 degrees C. Following incubation
      the plasma was separated into its lipoprotein and lipoprotein-deficient plasma
      (LPDP) fractions by three different methods and analyzed for BIRT 377 content by
      HPLC. For the rabbit studies New Zealand fasted white rabbits (3 kg; n=4) were
      administered an intravenous dose of free BIRT 377 (1 mg/kg). Following
      administration, serial blood samples were obtained and the plasma was analyzed
      for BIRT 377. The plasma conected at the 0.083-h time point was separated into
      each of its lipoprotein fractions and analyzed for BIRT 377. RESULTS: 37.8 +/-
      1.2% of the original drug amount incubated in rat plasma was recovered within the
      lipoprotein-rich fraction. 41.5 +/- 0.4% of the original chylomicron-associated
      drug concentration incubated was recovered within the lipoprotein-rich fraction.
      The percentage of drug recovered within the TRL fraction was significantly
      greater following the incubation of chylomicron-associated BIRT 377 compared to
      free BIRT 377. In addition, BIRT 377 apparently follows a two-compartment
      pharmacokinetic model following single intravenous dose administration to
      rabbits. CONCLUSIONS: These findings suggest that plasma lipoprotein binding of
      BIRT 377 is evident and may be a factor in evaluating the pharmacological fate of
      this drug when administered to patients that exhibit changes in their plasma
      lipoprotein lipid.

PMID- 11451040
TI  - Interaction mechanism between indoxyl sulfate, a typical uremic toxin bound to
      site II, and ligands bound to site I of human serum albumin.
AB  - PURPOSE: The study was performed for clarifying the mechanism of interaction
      between indoxyl sulfate (IS), a typical uremic toxin bound to site II, and site I
      ligands when bound to human serum albumin (HSA). The effect of the N to B
      transition on the interactions was also examined. METHODS: Quantitative
      investigation of the relations between ligands bound to HSA was performed by
      equilibrium dialysis, and the binding data were analyzed on the basis of a
      theoretical model for simultaneous binding of two ligands. RESULTS: The high
      affinity binding constants for the site I-ligands warfarin (WF) and dansyl-L
      asparagine (DNSA) increased with increasing pH, whereas those for the site II
      ligands IS and dansylsarcosine (DNSS) were hardly affected by pH. Mutual
      displacement experiments showed that even though IS binds to site II it
      influenced binding of DNSA at the azapropazone binding area in site I. By
      contrast, it is unlikely that IS affects the WF binding area of site I.
      Furthermore, pH-profiles showed that the interaction between IS and DNSA was very
      sensitive to the N to B transition: "competitive-like" strong allosteric
      regulation was observed for binding of the two ligands to the N conformer (pH
      6.5), whereas in the B conformation (pH 8.5) binding of these molecules was
      nearly "independent". CONCLUSIONS: The present data provide useful information
      for elucidating a potential mechanism of interaction between drugs and endogenous
      substances including uremic toxins.

PMID- 11451041
TI  - Influence of drug treatment on the microacidity in rat and human skin--an in
      vitro electron spin resonance imaging study.
AB  - PURPOSE: The possibilities of the noninvasive examination of microacidity (5) in
      different depths of the skin in vitro was explored, and the impact of drug
      treatment on the pH inside the skin was studied. METHODS: Spectral-spatial
      electron spin resonance imaging (ss-ESRI) and pH-sensitive nitroxides were used
      to obtain a pH map of rat and human skin in vitro. RESULTS: The dermal
      application of therapeutically used acids, such as salicylic acid and azelaic
      acid, caused a plain change of microacidity (pH) inside the skin. Species-linked
      differences between rat and human skin samples with respect to penetration and
      microacidity were found. CONCLUSIONS: ESRI has been shown to be a new and
      completely noninvasive method to monitor microacidity in different skin layers
      and on the skin surface. This nondestructive method allows serial measurements on
      skin samples to be performed without any preparatory steps.

PMID- 11451042
TI  - Synthesis and study of 5'-ester prodrugs of N6-cyclopentyladenosine, a selective
      A1 receptor agonist.
AB  - PURPOSE: A series of 5'-esters of N6-cyclopentyladenosine (CPA) were prepared
      with the aim to improve stability and bioavailability of selective A1 agonists.
      Log P values, stability, affinity, and activity toward human adenosine A1
      receptors were evaluated. METHODS: An appropriate synthetic procedure was adopted
      to avoid concomitant deamination at position 6. Log P values were obtained by the
      Mixxor system. The stability of CPA and its 5'-ester was evaluated in human
      plasma and whole blood and analyzed with high-performance liquid chromatography.
      The affinities to human A1 receptor expressed by N6-cyclohexyladenosine cells
      were obtained by binding experiments. The activities were evaluated by
      measurements of the inhibition of forskolin stimulated 3'-5'-cyclic adenosine
      monophosphate, performing competitive binding assays. RESULTS: All prodrugs were
      more lipophilic than CPA, and their hydrolysis, in whole blood and in plasma, was
      found related, respectively, to the length and hindrance of 5'-substituents.
      Affinity and activity values indicated a very weak interaction toward adenosine
      A1 receptor of the intact prodrugs. CONCLUSIONS: We propose 5'-esters of CPA,
      characterized by suitable lipophilicity and elevated degree of stability in
      physiological fluids, as possible candidates for CPA prodrugs.

PMID- 11451043
TI  - Population pharmacokinetic-pharmacodynamic model of craving in an enforced
      smoking cessation population: indirect response and probabilistic modeling.
AB  - PURPOSE: A population pharmacokinetic-pharmacodynamic model accounting for
      placebo effect was used to relate nicotine concentration and enforced smoking
      cessation craving score measured by the Tiffany rating scale short form. METHODS:
      Twenty-four smokers were enrolled in a placebo-controlled, randomized, double
      blind, three periods, crossover trial. The study objective was to describe the
      nicotine-induced changes on craving scores. Two modeling strategies based on a
      mechanistic (indirect response models with drug-related inhibition on the k(in)
      synthesis rate and with a drug-related stimulation of the k(out) removal rate
      were evaluated) and a probabilistic (logistic regression) approach were used.
      RESULTS: Placebo response model properly fitted the circadian changes on craving
      scores. The analysis revealed that the indirect response model with inhibition on
      k(in) was the preferred model for the smoking data whereas the preferred model
      for the Nicotine Replacement Therapy data was the one with stimulation on k(out).
      The logistic analysis showed that the nicotine concentration was a significant
      predictor of reduction in craving during the free-smoking period. CONCLUSIONS:
      Nicotine dosage regimen can influence the nicotine mechanism of action: an
      instantaneous delivery at an individually selected time seems to inhibit the
      onset of craving while constant delivery at a pre-defined time seems to attenuate
      the craving.

PMID- 11451044
TI  - Profound effect of plasma protein binding on the polarized transport of
      furosemide and verapamil in the Caco-2 model.

PMID- 11451045
TI  - Controlled release of insulin from injectable biodegradable triblock copolymer.

PMID- 11451046
TI  - Topographical and physicochemical modification of material surface to enable
      patterning of living cells.
AB  - Precise control of the architecture of multiple cells in culture and in vivo via
      precise engineering of the material surface properties is described as cell
      patterning. Substrate patterning by control of the surface physicochemical and
      topographic features enables selective localization and phenotypic and genotypic
      control of living cells. In culture, control over spatial and temporal dynamics
      of cells and heterotypic interactions draws inspiration from in vivo
      embryogenesis and haptotaxis. Patterned arrays of single or multiple cell types
      in culture serve as model systems for exploration of cell-cell and cell-matrix
      interactions. More recently, the patterned arrays and assemblies of tissues have
      found practical applications in the fields of Biosensors and cell-based assays
      for Drug Discovery. Although the field of cell patterning has its origins early
      in this century, an improved understanding of cell-substrate interactions and the
      use of microfabrication techniques borrowed from the microelectronics industry
      have enabled significant recent progress. This review presents the important
      early discoveries and emphasizes results of recent state-of-the-art cell
      patterning methods. The review concludes by illustrating the growing impact of
      cell patterning in the areas of bioelectronic devices and cell-based assays for
      drug discovery.

PMID- 11451047
TI  - Hydrodynamic damage to animal cells.
AB  - Animal cells are affected by hydrodynamic forces that occur in culture vessel,
      transfer piping, and recovery operations such as microfiltration. Depending on
      the type, intensity, and duration of the force, and the specifics of the cell,
      the force may induce various kinds of responses in the subject cells. Both
      biochemical and physiological responses are observed, including apoptosis and
      purely mechanical destruction of the cell. This review examines the kinds of
      hydrodynamic forces encountered in bioprocessing equipment and the impact of
      those forces on cells. Methods are given for quantifying the magnitude of the
      specific forces, and the response thresholds are noted for the common types of
      cells cultured in free suspension, supported on microcarriers, and anchored to
      stationary surfaces.

PMID- 11451048
TI  - Chinese population data in Beijing at 3 STR loci--CSF1PO, HUMTH01, and TPOX.

PMID- 11451049
TI  - Allele frequency distribution for six STR loci in Turkish population.

PMID- 11451050
TI  - Distribution of amplified fragment length polymorphism D1S80 alleles in Turkish
      population.

PMID- 11451051
TI  - Spanish population data on nine STR loci.

PMID- 11451052
TI  - Contributions of Ellis R. Kerley to forensic anthropology.
AB  - Ellis R. Kerley (1924 to 1998) represents an important figure in the history of
      American forensic anthropology. In research, he is best known for pioneering the
      microscopic approach to the estimation of age at death from human bone. A
      university professor for 22 years. Kerley also served as Scientific Director of
      the Army identification laboratory in Hawaii and worked on many forensic cases.
      He was a leader in the formation of the Physical Anthropology section of the AAFS
      and the American Board of Forensic Anthropology and held many offices within the
      AAFS, including President from 1990 to 1991.

PMID- 11451053
TI  - A career takes form: Ellis Kerley's tenure at the Armed Forces Institute of
      Pathology (1957-1966).
AB  - From 1957 to 1966, Ellis Kerley was employed at the Armed Forces Institute of
      Pathology (AFIP) in Washington, DC. Kerley worked in the Orthopedic Pathology
      section under the supervision of Lent C. Johnson, MD. As the only staff
      anthropologist at the AFIP, he lectured, conducted research, and consulted on
      forensic cases. His best-known research completed during these years was the
      osteon aging technique. He also conducted research and lectured on paleopathology
      and skeletal identification. Kerley's AFIP experience aided him in pursuing a
      distinguished career as a forensic scientist, within both academia and the
      federal government.

PMID- 11451054
TI  - A tribute to Dr. Ellis R. Kerley: the Kansas years.
AB  - Dr. Ellis R. Kerley, one of the founders of the Physical Anthropology section of
      the American Academy of Forensic Sciences, was born in Kentucky and received his
      undergraduate degree at the University of Kentucky. Following the completion of
      his doctoral degree (University of Michigan) he was a visiting professor at the
      University of Kentucky before joining the faculty at the University of Kansas in
      1966. At Kansas he was a major advisor for many graduate students who were to
      become leaders in the new area of Forensic Anthropology.

PMID- 11451055
TI  - Ellis Kerley's service to the military.
AB  - The purpose of this paper is to present the contributions Ellis Kerley has made
      to the United States Department of Defense in the area of forensic anthropology.
      His service began at the end of the Korean War in the identification laboratory
      established in Kokura, Japan, under the direction of T.D. Stewart. Ellis
      developed his research on the quantification of cortical bone microstructure as a
      means of age estimation while at the Armed Forces Institute of Pathology. In
      December 1985, Ellis was asked by the Army to form a commission to evaluate the
      Central Identification Laboratory, HI (CILHI). This lab is tasked with the
      mission of search and recovery and identification of American personnel killed or
      listed as missing from past military conflicts. Ellis's team reviewed the
      identification process and documentation, the qualifications of lab personnel,
      the adequacy of facilities and equipment, and some questionable cases. Their
      written report was supplemented with testimony in front of congressional
      committees. Ellis served as scientific director of CILHI from 1987 until 1991. In
      addition to overseeing the daily case work, he led several missions to Vietnam to
      examine human remains and served as spokesman for the lab. His input helped the
      lab gain needed scientific credibility. Despite the frustrations of trying to
      identify human remains within the Army's casualty and memorial affairs system,
      Ellis always maintained the utmost dignity, compassion, and respect for the
      victims and their families.

PMID- 11451056
TI  - Cranial change in Americans: 1850-1975.
AB  - This paper examines the pattern and magnitude of craniofacial change in American
      blacks and whites over the past 125 years. Standard metric data from 885 crania
      were used to document the changes from 1850 to 1975. Data from 19th century
      crania were primarily from anatomical collections, and 20th century data were
      available from the forensic anthropology data bank. Canonical correlation was
      used to obtain a linear function of cranial variables that correlates maximally
      with year of birth. Canonical correlations of year of birth with the linear
      function of cranial measurements ranged from 0.55 to 0.71, demonstrating that
      cranial morphology is strongly dependent on year of birth. During the 125 years
      under consideration, cranial vaults have become markedly higher, somewhat
      narrower, with narrower faces. The changes in cranial morphology are probably in
      large part due to changes in growth at the cranial base due to improved
      environmental conditions. The changes are likely a combination of phenotypic
      plasticity and genetic changes over this period.

PMID- 11451057
TI  - Stature, maturation variation and secular trends in forensic anthropology.
AB  - A twentieth-century trend for increased stature has received considerable
      attention in the forensic literature with regard to its effects on stature
      estimation, but a secular trend for earlier maturation has received little
      attention. Current evidence indicates that within populations with similar
      climatic adaptation, truncation or extension of the same trajectory of
      ontogenetic allometry accounts for the secular trend and the within-cohort
      stature variation, as well as the scaling of limb proportion to stature and
      intralimb proportions. Since secular increase is small compared to
      interindividual variation, the Trotter and Gleser formulae are still appropriate
      as long as the 95% confidence intervals are applied. A secular trend for
      increasing childhood and adolescent obesity is associated with a trend for
      accelerated skeletal maturation, but does not predict a consistent direction or a
      quantitative correction for traditional standards. Secular trends for increased
      stature and earlier maturation are overshadowed by increasing nonsecular
      intrapopulational variation.

PMID- 11451058
TI  - Racial variation in the proximal and distal femur: heritability and forensic
      utility.
AB  - The femur has been studied successfully by physical anthropologists for many
      years. Such traits as femoral head diameter and bicondylar width have been
      examined extensively and are of great value to forensic anthropologists and other
      skeletal biologists in sex identification. A number of studies over the past
      decade by the author and his former students have shown marked racial differences
      in the shape of the proximal femur and in at least one trait of the distal femur-
      intercondylar notch height. Anterior-posterior (AP) diameter of the proximal
      femur is much greater among Whites and Blacks than among East Asians and American
      Indians. Blacks have slightly greater intercondylar notch height than Whites.
      Other features, such as torsion, also differ between the major geographic racial
      populations. Current analysis suggests that the East Polynesians fall close to
      the American Indians and East Asians in the degree of flatness of the proximal
      femur. One study has tracked the degree of change in flatness during individual
      development, and finds little change within major populations from the youngest
      to the oldest individuals. Temporal changes within populations are likewise
      minimal. Two studies have examined sex differences within populations, which are
      also found to be very slight. Racial differences, on the other hand, are quite
      significant, and individuals of admixed ancestry fall intermediate between the
      two parental populations. Such suggestions of high heritability in the shape of
      the proximal and distal femur make these traits very useful in assessing ancestry
      in forensic contexts.

PMID- 11451059
TI  - Publications of Ellis R. Kerley (1924-1998).
AB  - Ellis R. Kerley (1924-1998) published at least 40 works between the years 1957
      and 1988. These include four reviews, 10 abstracts, 23 articles and book
      chapters, and three monographic works.

PMID- 11451060
TI  - Developing a quantitative extraction technique for determining the organic
      additives in smokeless handgun powder.
AB  - Compositional analysis of the organic additives in smokeless handgun powder can
      provide forensic information to associate known and questioned samples. A
      reliable method for the quantitative extraction of smokeless powder additives
      would strengthen these measurements. To achieve quantitative recovery, both
      supercritical fluid extraction (SFE) and ultrasonic solvent extraction (USE) were
      evaluated as candidate techniques. Following a detailed evaluation of the solvent
      choice, the recovery of spiked additive compounds, and the effect of the powder
      matrix, a reliable USE technique was developed. When quantitative USE recovery of
      the target analytes, nitroglycerin (NG), diphenylamine (DPA), and ethyl
      centralite (EC), is coupled with additive measurement by micellar capillary
      electrophoresis (CE), compositional information can be obtained in less than 1 h.

PMID- 11451061
TI  - A methodology based on NMR spectroscopy for the forensic analysis of condoms.
AB  - Both solution and solid state Nuclear Magnetic Resonance (NMR) spectroscopic
      techniques have been used to determine differences in commercially available
      condoms. Whilst solid state NMR is useful for determining the polymer backbone,
      it is not useful for forensic analysis due to the commonality of the latex
      condom. However solution NMR spectra obtained following a simple extraction
      procedure using hexane, provides a fingerprint of the additives in the
      lubricants. Following the development of a flow chart, basing decisions on the
      presence of particular peaks present in the solution spectra, 33 of 38 condoms
      could be individualized. Samples were also analyzed after having the lubricant
      manually removed and soaking the condom in water for 3 to 24 h. These experiments
      were performed to simulate a case of the sample having been used and disposed of
      by flushing down the toilet, as may be experienced in a case of a sexual assault.
      The results indicated that the only significant water soluble component was
      polyethylene glycol. The overall results suggest that the method developed may be
      a quick and useful technique in characterizing condoms. The information obtained
      can be used to provide associative evidence between suspect and crime, and so be
      useful in sexual assault cases.

PMID- 11451062
TI  - Comparison of transmission and internal reflection infrared spectra of cocaine.
AB  - Comparing the infrared transmission spectrum of cocaine HCl to its attenuated
      total reflection (ATR) spectrum has raised questions about the use of ATR spectra
      for forensic drug analysis. Whenever infrared spectra are collected using
      different modes or sample preparation methods, small variations in peak intensity
      ratios or peak positions are possible. These variations in infrared spectra are
      small and do not interfere with qualitative analysis, but they can cause
      confusion when unrecognized as normal effects of the different spectroscopic
      techniques. Comparison of the absorption and ATR spectra of cocaine hydrochloride
      illustrates the type of differences that can be expected. These differences are
      explained by the fundamental differences in the collection techniques. For the
      best quantitative results, only spectra collected by the same technique should be
      compared.

PMID- 11451063
TI  - A simple method for detection of gunshot residue particles from hands, hair,
      face, and clothing using scanning electron microscopy/wavelength dispersive X-ray
      (SEM/WDX).
AB  - We devised a simple and rapid method for detection of gunshot residue (GSR)
      particles, using scanning electron microscopy/wavelength dispersive X-ray
      (SEM/WDX) analysis. Experiments were done on samples containing GSR particles
      obtained from hands, hair, face, and clothing, using double-sided adhesive coated
      aluminum stubs (tape-lift method). SEM/WDX analyses for GSR were carried out in
      three steps: the first step was map analysis for barium (Ba) to search for GSR
      particles from lead styphnate primed ammunition, or tin (Sn) to search for GSR
      particles from mercury fulminate primed ammunition. The second step was
      determination of the location of GSR particles by X-ray imaging of Ba or Sn at a
      magnification of x 1000-2000 in the SEM, using data of map analysis, and the
      third step was identification of GSR particles, using WDX spectrometers. Analysis
      of samples from each primer of a stub took about 3 h. Practical applications were
      shown for utility of this method.

PMID- 11451064
TI  - Fibers under fire: suggestions for improving their use to provide forensic
      evidence.
AB  - The current emphasis on DNA technology in forensic science has led many to
      believe that trace evidence examinations, including fibers, may be of little
      value. Reasons are given here to show that this is an erroneous assumption. In
      the face of this situation, fibers examiners have been challenged to consider
      ways in which they can improve the services they offer to the Criminal Justice
      System not only by increasing the efficiency of the examinations, but also by
      expressing the evidential value of the findings in a clearer way. The separate
      stages within fibers casework from evidence collection to report writing are
      critically examined. Suggestions are made on how improvements may be achieved.
      Areas where particular progress can be made include improving communication and
      exchange of information between the investigator and the scientist and
      streamlining analysis by using the latest equipment in conjunction with effective
      case management. In addition, ways of making better use of existing data
      pertaining to fiber frequencies, accumulating new data by using the resources of
      working groups, and improving training procedures with respect to evidence
      interpretation are discussed.

PMID- 11451065
TI  - Human hair histogenesis for the mitochondrial DNA forensic scientist.
AB  - Analysis of mitochondrial DNA (mtDNA) sequence from human hairs has proven to be
      a valuable complement to traditional hair comparison microscopy in forensic cases
      when nuclear DNA typing is not possible. However, while much is known about the
      specialties of hair biology and mtDNA sequence analysis, there has been little
      correlation of individual information. Hair microscopy and hair embryogenesis are
      subjects that are sometimes unfamiliar to the forensic DNA scientist. The
      continual growth and replacement of human hairs involves complex cellular
      transformation and regeneration events. In turn, the analysis of mtDNA sequence
      data can involve complex questions of interpretation (e.g., heteroplasmy and the
      sequence variation it may cause within an individual, or between related
      individuals. In this paper we review the details of hair developmental histology,
      including the migration of mitochondria in the growing hair, and the related
      interpretation issues regarding the analysis of mtDNA data in hair. Macroscopic
      and microscopic hair specimen classifications are provided as a possible guide to
      help forensic scientists better associate mtDNA sequence heteroplasmy data with
      the physical characteristics of a hair. These same hair specimen classifications
      may also be useful when evaluating the relative success in sequencing different
      types and/or forms of human hairs. The ultimate goal of this review is to bring
      the hair microscopist and forensic DNA scientist closer together, as the use of
      mtDNA sequence analysis continues to expand.

PMID- 11451066
TI  - Distortion of teatree stems by twine as a means to determine the number of years
      that the stems have been used to support cannabis plants.
AB  - In New Zealand, stems of teatree (Kunzea/Leptospermum) growing around illicit
      cannabis plots have been used to anchor lengths of twine running through the
      plots to hold cannabis plants upright. Forensic examinations of distortions of
      teatree stems caused by the twine have been carried out to determine when the
      twine had been first tied around the stems, in order to estimate the number of
      years that plots have been in operation. In this experiment, baling twine was
      tied around stems of a teatree (Kunzea ericoides) and the effect monitored for a
      period of three years. Varying degrees of stem distortion occurred during the
      first year, caused initially by expansion of callus (a wound tissue) rather than
      constriction of the growth (annual) rings of the xylem. Although this callus has
      a type of growth ring, these are not annual, therefore cannot be used to
      determine the number of years that stems have had twine attached. Xylem growth
      rings of the teatree in this experiment were not restricted until the third year.
      Distortion of teatree stems allows the determination of a minimum (not absolute)
      number of years that twine has been attached.

PMID- 11451067
TI  - Interpapillary lines--the variable part of the human fingerprint.
AB  - The dermatoglyphic pattern of human palms and soles is individually unique and
      unchanging. Their prints show the course of the papillary ridges as papillary
      lines. Case reports and a few older studies of repeatedly taken fingerprints
      could, however, show that so-called interpapillary lines can develop between the
      papillary lines. The questions of this study were: How often do interpapillary
      lines occur? Can the differences between papillary and interpapillary ridges be
      quantified? Five-hundred and two ink prints of the palms and fingers from the
      archive of the Bochum Police Department were examined retrospectively. In 121
      volunteers, the appearance of interpapillary lines was examined prospectively.
      From the later collective, the fingerprints of 13 people with interpapillary
      lines and nine people without were examined further by taking two silicon prints
      and measuring them with laser profilometry In 215 of the 502 ink prints (42.8%)
      interpapillary lines could be demonstrated. In those subjects younger than 20
      years they were less frequently observed (34.1%) than in those above the age of
      20 (51.8%). In all cases using laser profilometry the interpapillary lines could
      be related to a corresponding interpapillary ridge. The interpapillary ridge
      heights were 24.9 +/- 10.0 microm, significantly lower than the papillary ridges,
      which measured 59.0 +/- 19.2 microm. Interpapillary ridge widths were with 194.8
      +/- 65.1 microm significantly narrower as compared to 435.5 +/- 57.4 microm in
      the papillary ridge. Those papillary ridges, between which interpapillary ridges
      were found, were significantly further apart from each other (610.5 +/- 78.9
      microm) than those without interpapillary ridges (484.9 +/- 70.6 microm). During
      the course of a lifetime new ridges between the regular papillary ridges can
      develop or manifest. The fact that interpapillary lines are more frequently found
      on the right hands in men and those with increasing age is consistent with the
      theory that they correspond to degenerative changes and with sensitivity of
      touch.

PMID- 11451068
TI  - Length variation in HV2 of the human mitochondrial DNA control region.
AB  - Hair samples were typed from three individuals who exhibited length heteroplasmy
      in the homopolymeric cytosine stretches (C-stretch) in hypervariable region 2
      (HV2). The study demonstrated that for different hairs within an individual, the
      HV2 C-stretch region can vary with respect to the number of cytosines and/or
      proportion of C-stretch length variants. Length heteroplasmy may occur regardless
      of the prominent length variant present in this region. Differences in the number
      of cytosines at the C-stretch region, or a variation in the relative amounts of
      heteroplasmic length variants, cannot be used to support an interpretation of
      exclusion.

PMID- 11451069
TI  - Development of latent fingerprints on metallic surfaces using
      electropolymerization processes.
AB  - We propose a new process for developing latent fingerprints on metal items,
      applicable to unfired weapons made of Ergal in particular. The method is based on
      the presence of fatty acids that are contained in fingerprints and act as an
      insulator on the surface where fingerprints are to be developed. The process of
      polymerization occurs on the metal portions left untouched by finger contact.
      Hence, the developing process results as a negative pattern of the original
      fingerprint. The reaction consists in the electropolymerization of pyrrole and
      substituted porphyrins, i.e., tetra (o-aminophenyl) porphyrine: radical-cations
      are generated on superficial nucleation sites by oxidation of monomer, close to
      the electrode surface; subsequently, the radical species react with the neutral
      monomer, which begins to diffuse to the electrode. We have also studied the
      polymer's morphology by means of SEM and AFM, in order to find a correlation
      between the reagent to be used and the quality of the enhancement process. These
      are only preliminary results; however, they show that the suggested method is a
      new way to increase the rate of success in developing latent fingerprints on
      metal surfaces. In this regard, it may be considered complementary to other
      conventional procedures, due to the low costs of the instruments and reagents,
      and the rapidity and simplicity of the treatment.

PMID- 11451070
TI  - Evaluation of principal components analysis with high-performance liquid
      chromatography and photodiode array detection for the forensic differentiation of
      ballpoint pen inks.
AB  - Inks from seven black and eight blue ballpoint pens were separated by a high
      performance liquid chromatography (HPLC) method utilizing a photodiode array
      detection (PDA). A classifier flowchart was designed for the chromatographic data
      based on the presence or absence of certain peaks at different wavelengths to
      qualitatively discriminate between the inks. The same data were quantitatively
      classified by principal components analysis (PCA) to estimate the separation
      between a pair of classes of ink samples. It was found that the black ballpoint
      pen inks were discriminated satisfactorily utilizing two-dimensional data of the
      peak areas and retention times at the optimum wavelengths. The blue pens were
      discriminated by analyzing the chromatographic data at four different wavelengths
      simultaneously with a cross-validated PCA. The results of this study indicated
      that HPLC-PDA coupled with chemometrics could make a powerful discriminating tool
      for the forensic chemist, especially when analyzing extensive and/or complex
      data.

PMID- 11451071
TI  - Signature authentication by forensic document examiners.
AB  - We report on the first controlled study comparing the abilities of forensic
      document examiners (FDEs) and laypersons in the area of signature examination.
      Laypersons and professional FDEs were given the same signature
      authentication/simulation-detection task. They compared six known signatures
      generated by the same person with six unknown signatures. No a priori knowledge
      of the distribution of genuine and nongenuine signatures in the unknown signature
      set was available to test-takers. Three different monetary incentive schemes were
      implemented to motivate the laypersons. We provide two major findings: (i) the
      data provided by FDEs and by laypersons in our tests were significantly different
      (namely, the hypothesis that there is no difference between the assessments
      provided by FDEs and laypersons about genuineness and nongenuineness of
      signatures was rejected); and (ii) the error rates exhibited by the FDEs were
      much smaller than those of the laypersons. In addition, we found no statistically
      significant differences between the data sets obtained from laypersons who
      received different monetary incentives. The most pronounced differences in error
      rates appeared when nongenuine signatures were declared authentic (Type I error)
      and when authentic signatures were declared nongenuine (Type II error). Type I
      error was made by FDEs in 0.49% of the cases, but laypersons made it in 6.47% of
      the cases. Type II error was made by FDEs in 7.05% of the cases, but laypersons
      made it in 26.1% of the cases.

PMID- 11451072
TI  - Differences in morphological age-related dental changes depending on postmortem
      interval.
AB  - Morphological methods for age estimation from teeth have been developed and
      applied to samples without taking the postmortem interval into consideration. We
      studied differences in morphological age-related changes between fresh extracted
      teeth and teeth from human skeletal remains in order to develop appropriate
      dental age estimation methods according to the time after death. Forty-three
      permanent teeth from dental patients were compared to 37 teeth obtained from
      human skeletal remains with a postmortem interval from 21 to 37 years.
      Morphological age-related changes were investigated by measuring variables on
      intact and half-sectioned teeth. A new computer assisted image analysis procedure
      to avoid subjectivity was developed to measure variables in sectioned specimens.
      Dental color, translucency length, attrition, cementum apposition, and secondary
      dentin showed higher values in teeth from human skeletal remains than in fresh
      extracted teeth. Variables obtained by morphometric analysis of computer
      generated images (tooth length, tooth width, root length, and root area) showed
      higher values in fresh extracted teeth than in teeth from skeletal remains. The
      postmortem interval affects age-related morphological changes, and therefore
      different methods should be used for teeth of unknown postmortem interval.

PMID- 11451073
TI  - Dental age estimation in Belgian children: Demirjian's technique revisited.
AB  - AIM: The purpose of this study was to evaluate the accuracy of Demirjian's dental
      age estimation in children in a Belgian Caucasian population and to adapt the
      scoring system in case of a significant overestimation as frequently reported. We
      selected 2523 orthopantomograms of 1265 boys and 1258 girls, of which 2116 (1029
      boys and 1087 girls) were used for estimating the dental age with the Demirjian's
      technique. The 407 other orthopantomograms were beyond the original age limit. A
      second sample of 355 orthopantomograms was used to evaluate the accuracy of the
      original method and the adapted method. A signed-rank test was performed to
      search for significant age differences between the obtained dental age and the
      chronological age. A weighted ANOVA was performed in order to adapt the scoring
      system for this Belgian population. The overestimation of the chronological age
      was confirmed. The adapted scoring system resulted in new age scores expressed in
      years and in a higher accuracy compared to the original method in Belgian
      Caucasians.

PMID- 11451074
TI  - Factors in prison suicide: one year study in Texas.
AB  - The goal of the study was to examine psychopathology and stressors suffered by
      suicide victims, and to describe the characteristics of the suicides in the Texas
      Department of Criminal Justice between June of 1996 to June of 1997. Data on 25
      completed suicides were collected from the records department. RESULTS: The
      authors identified 60% of the suicide victims with a history of psychiatric
      disorders. Seventy-six percent had been diagnosed with psychiatric disorders
      while incarcerated. The most frequent psychiatric disorders were mood disorders
      (64%), psychotic disorders (44%), personality disorders (56%), and comorbidity
      with a history of presentencing alcohol and drug abuse was common. Most of the
      victims experienced chronic and/or acute stressors of acute trauma, disrupted
      relationship, sentence hearing, and/or medical condition. We concluded that
      important factors associated with increased risk of prison suicide include
      psychiatric disorders, comorbid substance abuse, a history of suicide attempt,
      and chronic and/or acute stressors.

PMID- 11451075
TI  - Child and adolescent suicide in a large, urban area: psychological, demographic,
      and situational factors.
AB  - We examined all completed suicides by children and adolescents in Los Angeles
      County who died during 1996 and 1997. There were 46 subjects, aged 11 through 16.
      The majority of the decedents were males and over age 14. The predominant racial
      group was Hispanic. There was an almost even split between firearms and hanging
      as the means of death. Females had a statistically significantly higher rate of
      prior suicide attempts than males. Over one-third left a suicide note, almost one
      half were noted to be depressed, and 22% tested positive for alcohol or illicit
      drugs. Less than one-quarter were in mental health treatment. Eighty-seven
      percent had difficulty transitioning to or during adolescence; e.g., problems at
      home, legal and school difficulties, and relationship losses. These findings are
      discussed in terms of Eriksonian developmental theory. We offer recommendations
      for intervention and prevention of suicide.

PMID- 11451076
TI  - Fingerprinting the deceased: traditional and new techniques.
AB  - Identification of the deceased is an important task in medicolegal
      investigations. Fingerprints rank as the most widely used identification method,
      although obtaining the prints from the cadaver is not always easily accomplished.
      Various techniques for fingerprinting decomposed, mummified and burn victims have
      been suggested in the literature. In the present review, the diverse
      fingerprinting procedures implemented for cadavers in various conditions, with an
      emphasis on mummified fingers, are presented.

PMID- 11451077
TI  - Septo-optic dysplasia and unexpected adult death--an autopsy approach.
AB  - A 20-year-old woman who suffered from septo-optic dysplasia died unexpectedly
      following a presumed viral gastroenteritis. Autopsy and neuropathological
      examination confirmed optic nerve hypoplasia with absence of the septum
      pellucidum. Marked adrenal gland hypoplasia reflected hypothalamic
      hypopituitarism. The small and large intestines were dilated and filled with
      liquid fecal material. This case demonstrates that individuals with septo-optic
      dysplasia may be at risk of unexpected death at all ages. The complexity of
      mechanisms of death in rare dysmorphic conditions may be overlooked if relevant
      clinical information is not available at the time of autopsy and unless specific
      steps are taken to clearly delineate the underlying features of the condition.

PMID- 11451078
TI  - Detection of benzodiazepines in different tissues, including bone, using a
      quantitative ELISA assay.
AB  - Benzodiazepines were analyzed in different tissue samples, including hone, by
      ELISA. The sensitivity of detection for different benzodiazepines was consistent
      with the manufacturer's reports of the cross reactivities of the antibodies used,
      with the greatest sensitivity for midazolam and the least for diazepam; in
      addition the pharmacokinetics was consistent with the known duration of action of
      the different benzodiazepines, with midazolam cleared rapidly, and diazepam
      slowly. Following intramuscular injection of 300 microg of midazolam at 16 h
      intervals for ten days, the drug was detectable in bone tissue samples obtained
      from skeletonized remains buried in soil at room temperature for three weeks.

PMID- 11451079
TI  - GHB and driving impairment.
AB  - Gamma hydroxybutyrate (GHB) was identified in the blood of 13 subjects arrested
      for impaired driving. GHB concentrations ranged from 26 to 155 mg/L (mean 87
      mg/L, median 95 mg/L). In eight cases, GHB was the only drug detected, and signs
      of impairment were consistent with those of a CNS depressant, including erratic
      driving (weaving, swerving, ignoring road signs), confusion, incoherent speech,
      unresponsiveness, lack of balance, unsteady coordination, poor performances on
      field sobriety tests, and varying states of wakefulness. Given the ability of GHB
      to induce sleep and unconsciousness, it is evident from these cases that
      recreational use of the drug has the potential to impair a person's driving
      ability.

PMID- 11451080
TI  - Measurements of ulna--a new method for determination of sex.
AB  - Identification of sex from skeleton parts is of paramount importance to
      medicolegal investigations. The present study makes an attempt to assess sex from
      the ulna by devising new measurements for fragmentary bones. Dry and adult ulnae
      (100 male and 60 female) of Madhya Pradesh, India were subjected to three
      measurements (Olecranon--coronoid angle, length, and width of inferior medial
      trochlear notch) that were devised specifically for this study. The data were
      analyzed using discriminant function analysis. Direct analysis using single or
      multiple variables revealed the Olecranon-Coronoid angle as the best single
      parameter, yielding 85% accuracy. Measurements of the inferior medial trochlear
      notch have an additional advantage of being used in fragmentary bone where only
      the upper end is available. The calibrated discriminant functions correctly
      classified 90.6% of all males and females in an independent test sample.

PMID- 11451081
TI  - Machine washing or brushing of clothing and its influence on shooting distance
      estimation.
AB  - Experiments were conducted to assess the effect of machine washing or brushing of
      clothing items on Gunshot Residue (GSR) patterns (gunpowder residues, lead, and
      copper, deposits) around bullet entrance holes. Results show that those
      treatments decrease considerably the amount and density of GSR. However, for
      close shooting distances not all of the GSR deposits are removed. Remaining
      patterns may be visualized by specific color reactions and used for shooting
      distance estimation.

PMID- 11451082
TI  - Headspace/solid-phase microextraction/gas chromatography-mass spectrometry: a
      screening technique for the recovery and identification of volatile organic
      compounds (VOC's) in postmortem blood and viscera samples.
AB  - This paper describes the application of Headspace/Solid-Phase Microextraction/Gas
      Chromatography-Mass Spectrometry (HS/SPME/GC-MS) to the recovery and
      identification of volatile organic compounds in blood and viscera samples from
      deceased persons. The technique is used as a screening procedure to rapidly
      obtain information relating to toxicological investigations. The technique is
      suitable for the detection of volatiles (of wide boiling range) including butane,
      halothane, toluene, xylenes, and petrol residues in blood and viscera (lung,
      brain, and body fat).

PMID- 11451083
TI  - Pollen on grass clippings: putting the suspect at the scene of the crime.
AB  - In a case of alleged sexual assault, the pollen content of samples of grass
      clippings and soil from the suspect's clothing and shoes was compared to that of
      a sample of grass clippings from the alleged crime scene (a grassy area) to
      determine whether or not the suspect had been at the scene. The clothing and shoe
      samples showed a very strong correlation with each other and with the sample from
      the alleged crime scene in the combination of the different types of pollen
      present, very strongly supporting the contention that the suspect had been at the
      scene.

PMID- 11451084
TI  - The forensic examination of a fire-damaged vehicle.
AB  - The Lothian and Borders Police Forensic Science Laboratory was asked to assist in
      the investigation of a suspected fraudulent insurance claim involving a fire
      damaged motor vehicle. This case demonstrates the persistence of fire accelerants
      when confined, and the reproducible nature of volatiles created from the
      accelerated burning of a synthetic material.

PMID- 11451085
TI  - Digital enhancement of sub-quality bitemark photographs.
AB  - Digital enhancement software was used to enhance bitemark photographs. This
      enhancement technique improved the resolution of the bitemark images. Lucis was
      the software program utilized in this study and case applications. First, this
      technique was applied on known bitemark images to evaluate the potential
      effectiveness of this digital enhancement method. Subsequently, Lucis was
      utilized on two separate unsolved cases involving enhancement of bitemark
      evidence. One case involved a severely beaten infant with a bitemark on the upper
      thigh. The second case involves a bitemark observed on the breast of a female
      sexual assault strangulation victim. In both cases, bitemark images were
      significantly improved after digital enhancement.

PMID- 11451086
TI  - Fatal cervical necrotizing fasciitis (a report of two cases of confirmed
      odontogenic origin and one of possible odontogenic origin).
AB  - Three cases of cervical necrotizing fasciitis (CNF), two of confirmed odontogenic
      origin and one of probable odontogenic origin, were observed from 1993-1999. This
      is in addition to three cases previously reported by this office. A rare sequelae
      of dental infection, CNF can be a severe, rapidly progressing infection of the
      cervical tissues having a mortality rate of up to 50%. "Hospital gangrene" was
      first described during the Civil War. It was later to be described as necrotizing
      fasciitis and later yet was designated as a separate clinicopathological
      diagnosis.

PMID- 11451087
TI  - An unusual case of suicide by means of a pneumatic hammer.
AB  - We describe an extraordinary case of a 49-year-old man who committed suicide by
      using a pneumatic hammer. As an industrial accident was initially assumed,
      difficulties in determining the manner of death are discussed. In addition, the
      ability to perform activity and evidence of a protracted agony in a situation of
      extensive cerebral destruction are considered. To our knowledge, no such case of
      suicide has ever been reported.

PMID- 11451088
TI  - Blunt pancreatic trauma by a wheelchair user restraint system during a traffic
      accident.
AB  - Traffic accidents are the most common cause of blunt pancreatic trauma, and most
      injuries occur in unrestrained drivers. Blunt pancreatic trauma in a passenger or
      a restrained driver is rare. In this report, we describe a case of blunt
      pancreatic trauma caused by a restraint system for wheelchair users during a
      traffic accident.

PMID- 11451089
TI  - Using decision science to gain insight into ethical issues: an example involving
      thresholds in workers' compensation.
AB  - Systematically analyzing and comparing the ethical dimensions of policy-decision
      alternatives is remarkably difficult. The ethical implications of a set of
      decision alternatives, as well as the ranking of that set, are subject to any
      number of quantitative and qualitative variables, not the least of which is
      differing individual interpretation. In spite of this, decision science offers a
      consistent, transparent framework from which to analyze the ethical components
      and implications of policy decisions. Workers' Compensation insurance programs
      are state-governed systems of insurance in which workers, in exchange for giving
      up the right to sue their employer and their coemployees, receive some
      compensation if they are injured on the job, without regard as to who was at
      fault. Importantly, Workers' Compensation does not compensate workers for all
      losses. Thus, injured workers often sue those who provide goods and services to
      their employer's production system. Different states set different thresholds
      relating to who can be brought into such a lawsuit and under what conditions a
      sued means-of-production entity can, in turn, bring the injured party's employer
      into the suit as a third-party defendant. Forensic engineers are often involved
      in such lawsuits to evaluate whether or not a given component of a production
      system is or is not defective. Using Workers' Compensation as an example, this
      paper explores the methodology and the difficulty of quantifying the ethical
      implications of policy decisions by examining the concept of thresholding a
      policy variable. Thresholding will be defined and the ethical effect on the
      various parties of varying a policy threshold will be discussed.

PMID- 11451090
TI  - Scientific certainty: research versus forensic perspectives.
AB  - The scientific community and the judicial system are different components of
      society with different structures and functions. Nevertheless, science can
      contribute relevant and useful information to judicial deliberations if the
      inherent limitations of that information are understood. These limitations stem
      from the way the information is presented and perceived both by those who are
      providing it and those who are providing the context in which it is presented.

PMID- 11451091
TI  - Law, ethical codes, and the report of the CSSP survey on ethics policies. Council
      of Scientific Society Presidents.
AB  - Recently, the Council of Scientific Society Presidents (CSSP) collected data from
      its member organizations regarding codes of ethics. To better understand why such
      a survey would be undertaken, this paper begins by examining what is meant by
      ethics and highlights some distinctions between law and ethics. It then discusses
      codes of ethics, stressing their purposes and functions. Finally, it looks at the
      results of the CSSP survey and evaluates how various organizations formulate and
      implement their codes.

PMID- 11451092
TI  - Am I my brother's (or customer's or tenant's) keeper? Economic and ethical
      aspects to the California Supreme Court's struggle with the issue of landowner's
      standard of care.
AB  - The Supreme Court of California has ruled on several cases involving the question
      of to what extent a possessor of land is liable for the harm to customers or
      tenants occurring when a third party commits a criminal act against the customers
      or tenants present on the land. This paper reviews the historical development of
      this aspect of negligence law and analyzes the ethical and economic efficiency
      implications of ascribing legal responsibility for such crimes to: a) local
      government, b) the possessor of land, c) the customer, and d) the criminal. For
      example, is there an effort by the judicial system to substitute deterrence from
      criminal acts provided by possessors of land (i.e., specific deterrence) for the
      general deterrence traditionally provided through the use of police powers by
      local government? Analysis indicates that specific deterrence may be more
      effective in changing the location of criminal acts than in reducing the level of
      criminal activities. Also, the expense of complying with the legal
      responsibilities of protecting customers and clients may be especially high in
      high-crime, low-income areas, thus forcing commercial establishments to move or
      go out of business. Thus, we have a troubling tradeoff: compensating individual
      crime victims in a high-crime area could ultimately deprive the residents of
      basic economic opportunities.

PMID- 11451093
TI  - Gene frequencies of 12 STR loci in an endogamous Badaga population (South India).

PMID- 11451094
TI  - Allele frequency distribution of three STR loci (CSF1PO, TPOX, and TH01) in a
      Brazilian population sample.

PMID- 11451095
TI  - Allele frequencies for the PowerPlex 16 STR loci in an Albanian population sample
      from northern Italy.

PMID- 11451096
TI  - Segmental anatomy of the temporal bone.
AB  - More of us suffer from hearing loss than from visual impairment, coronary artery
      disease, and cancer combined. Auditory dysfunction is detected in less than one
      third of newborns afflicted and is underdiagnosed in the elderly. Despite
      biomedical and technological advances, our understanding of vestibular
      dysfunction has grown little. Forming part of the lateral and inferior surfaces
      of the skull, the temporal bone contains the organs of hearing and balance.
      Diagnosis of diseases in these important regions requires adequate clinical
      information and a thorough knowledge of normal temporal bone anatomy to recognize
      abnormal findings when present. This article dissects the temporal bone into
      segments, describes the relevant radiologic anatomy of each, and discusses the
      imaging appropriate to specific concerns.

PMID- 11451097
TI  - Temporal bone trauma.
AB  - Temporal bone trauma has numerous manifestations, many of which are detectable by
      current imaging techniques. Our discussion of temporal bone trauma is subdivided
      into fractures and pseudofractures, fistulous communication, hearing loss, and
      facial nerve involvement.

PMID- 11451098
TI  - Imaging evaluation of sensorineural hearing loss.
AB  - The imaging evaluation of patients with sensorineural hearing loss (SNHL) focuses
      on the acoustic pathways from the cochlea to the auditory cortex. Magnetic
      resonance imaging (MRI) is the modality of choice for most patients with SNHL,
      though computed tomography (CT) also plays an important role in the evaluation of
      bony changes and in patients for whom MRI is contraindicated. Conventional
      enhanced MRI is the most commonly used technique in this clinical setting. High
      resolution fast spin-echo T2 MRI is an adjunctive technique that provides
      exquisite evaluation of the cerebellopontine angle (CPA), internal auditory canal
      (IAC), cranial nerves, and membranous labyrinth, and plays a significant role in
      the diagnosis and surgical evaluation of SNHL. Categories of lesions that cause
      SNHL include brain lesions involving central auditory pathways; neoplasms of the
      CPA and IAC, the most common being schwannoma; other neoplastic, congenital, and
      cystic masses of the CPA and IAC; congenital anomalies of the inner ear;
      intrinsic cochlear nerve defects, inflammatory processes of the inner ear; and
      temporal bone trauma.

PMID- 11451099
TI  - Pulsatile and nonpulsatile tinnitus: a systemic approach.
AB  - Tinnitus is an annoying symptom that affects approximately 10% of the population.
      Unfortunately, in more than 60% of patients, even an extensive workup may not
      lead to diagnosis, partly because of the diverse causes of the symptom. The
      imaging protocol study should therefore be adapted to the history of the patient,
      and each imaging study should underline which etiologies it may exclude. Imaging
      studies should only be performed after a careful clinical examination and
      otoscopy. Some characteristic clinical findings are suggestive of such etiologies
      as pulsed synchronous tinnitus or positional tinnitus, varying with the venous
      pressure. History of associated neurological deficits, nerve palsies, trauma,
      ischemic attacks, and visual disturbance (in overweight women) may modify the
      imaging protocol. Study of the brain and the cervical vessels should always be
      included to rule out a benign intracranial hypertension. Path and size of the
      internal carotid artery should be systematically described with regard to the
      size of the jugular vein and presence of emissary veins. Objective pulsatile
      tinnitus and tinnitus in children always need a careful imaging study.

PMID- 11451100
TI  - Imaging of the windows of the temporal bone.
AB  - Imaging of the window of the temporal bone has became an important tool in the
      analysis of hearing loss, vertigo, tinnitus in a context of trauma, malformation,
      otosclerosis, and chronic otitis media. A good knowledge of the anatomy and a
      good technical procedure are necessary for making an efficient diagnosis. The
      increased thickness of the footplate may be delineated in otosclerosis, chronic
      otitis media, malformation, when it is measured at 0.7 mm or more in horizontal
      computed tomography (CT) sections. The traumatic displacement of the stapes,
      particularly within the labyrinths, is easily diagnosed in horizontal CT section.
      Imaging of the round window is now very important for the detection of
      otosclerotic foci, congenital stenosis, and perilymphatic fistula with or without
      fracture. Magnetic resonance imaging (MRI) with the high-resolution T2 plays an
      important role in the detection of a small amount of fluid in the round window
      recess, confirming the traumatic perilymphatic fistula without fracture.

PMID- 11451101
TI  - Framing the nicotine debate: a cultural approach to risk.
AB  - This study examined Congressional testimony concerning regulation of tobacco
      advertising by 3 policy factions representing industry, government, and lay
      activists. On the basis of the cultural theory of risk, policy disputants were
      divided into entrepreneurial, bureaucratic, and egalitarian communities, each
      with a distinct cosmology that impedes discourse among the groups. The authors
      examined ways in which the 3 policy factions framed the tobacco advertising
      issues to see the extent to which such unique cosmologies were expressed or
      whether mutual frames might signal opportunities for negotiation among the
      interest groups. Major themes in the testimony were identified through semantic
      network analysis and clustering of associated words that revealed discourse
      patterns peculiar to each group and reflective of their cultural biases toward
      health risk. Semantic network analysis can be a tool to clarify these
      presuppositions and unmask relations among factions, thereby bridging policy
      solutions across interest groups.

PMID- 11451102
TI  - Networking, coping, and communicating about a medical crisis: a phenomenological
      inquiry of transplant recipient communication.
AB  - Through a phenomenological framework, the authors attempt to shed light on the
      communication processes of organ transplant recipients when discussing
      transplantation and related topics. Eight essential themes (awareness, support,
      commitment, pride, education, mentoring, comparison, and community) emerged from
      37 participants as central to the communicative experiences of transplant
      recipients and their families. Additional insight was generated through a 2nd
      tier of focus group discussions resulting in a proposed model of transplant
      recipient communication. An interpretation of the model, implications for future
      research, and implications for praxis are presented.

PMID- 11451103
TI  - Framing women's health with a sense-making approach: magazine coverage of breast
      cancer and implants.
AB  - This study examined how women's magazines framed breast cancer and silicone
      implants to determine whether they used a sense-making framework. Sense-making
      calls for existing gaps to be closed between what one group views as real and
      what another group experiences (Parrott, 1996). Analysis included 86 articles on
      cancer and implants published in four women's magazines from 1990 to 1997.
      Overall findings suggest that women's magazines used a sense-making approach to
      cancer coverage, framing the disease in terms of coping with its effects,
      personal experiences, and risk factors. Themes in implant articles pertained to
      economic concerns of the medical industry and media.

PMID- 11451104
TI  - Drench effects of media portrayal of fatal virus disease on health locus of
      control beliefs.
AB  - Drawing on the notion of the drench hypothesis proposed by Greenberg (1988), the
      author proposes a preliminary theoretical framework to explain "drenching"
      effects of dramatic media. Three drench variables-perceived realism, role
      identification, and media involvement-were identified and tested regarding their
      role in mediating the impact of virus disease portrayals on health locus-of
      control belief orientations. Participants in the experimental condition watched
      the movie Outbreak (a portrayal of an outbreak of a deadly virus disease).
      Perceived realism, role identification, and media involvement were measured
      concerning the movie depiction of the virus disease. The findings indicate that
      the dramatized portrayal significantly weakened the viewers' beliefs in self
      controllability over health and strengthened their beliefs in chance outcomes of
      health. Beliefs in provider control over health were affected by the viewers'
      perception of realism regarding the movie portrayals. Effects of role
      identification were different between male and female viewers. The results are
      discussed in relation to drench analysis as a theoretical approach to media
      effects.

PMID- 11451105
TI  - Informing women about their breast cancer risks: truth and consequences.
AB  - We assessed the extent to which informing women about their risk for breast
      cancer affected their perceived 10-year and lifetime risks for getting breast
      cancer, their emotional reactions toward getting breast cancer, and their
      intentions to get mammograms. In a pre- to posttest design, 121 women were given
      their 10-year risk of getting breast cancer with or without being compared with
      women their age and race at lowest risk. Women's perceptions of their 10-year
      risks became more congruent (i.e., more accurate) with their actual risk.
      Participants were more accurate when they received their own risk without being
      compared with women at lowest risk. Women who received only their own risk
      estimate reported being at lower risk than other women. Overall, women reported
      that obtaining their 10-year risk estimate either did not affect or increased
      their intentions to get mammograms. These results suggest that giving women their
      individual risk of getting breast cancer improves accuracy while also enhancing
      their feelings that they are at lower risk than other women. Counter to many
      theories of health behavior, reducing women's perceived risk of breast cancer did
      not lower their intentions to get mammograms. Implications for the communication
      of breast cancer risk are discussed.

PMID- 11451106
TI  - Total condylar knee replacement: a 20-year followup study.
AB  - Between 1976 and 1979, 220 total knee replacements were done on 164 patients
      using the Total Condylar Knee replacement. The diagnosis was rheumatoid arthritis
      in 111 knees and osteoarthritis in 109 knees. Patients with 157 knees are known
      to have died as of December 1998, leaving 63 knees in patients who are still
      alive. Twelve patients with 18 knees were lost to followup. The average 20-year
      followup data (range, 18-22 years) are presented for 45 knees in 30 patients
      using Knee Society evaluations. The average Knee Society clinical score for the
      surviving patients was 88 points, and the average functional score was 58 points.
      The radiographic followup averaged 19 years. The average overall alignment was 3
      degrees valgus. Femoral lucencies were present in 17 of 40 adequate lateral
      views, most commonly about the anterior and posterior surfaces. Two femoral
      components were loose. Twenty-two tibial components had radiolucencies; four
      radiolucencies were circumferential. The remaining 41 knees retained a well-fixed
      cemented central peg despite proximal interface lucencies. From the group of 220
      knees, 14 revisions have been done at an average of 11.4 years postoperative. Two
      knee replacements were revised for isolated tibial loosening, whereas one knee
      replacement had isolated femoral loosening. Three knee replacements were revised
      for loosening of both components, and one was revised for isolated patellar
      loosening. Four patients had sepsis develop; three of these four patients were
      treated with two-stage revision, and one underwent fusion. Three patients were
      treated for supracondylar fractures. The Total Condylar Knee replacement
      maintains excellent durability at 20-years followup.

PMID- 11451107
TI  - Metal-backed patellar components: a brief report on 10-year survival.
AB  - Two hundred ninety-six total knee arthroplasties were performed with metal-backed
      patellar components in 206 patients with an average followup of 10 years. These
      total knee arthroplasties were reviewed retrospectively for survivorship,
      failure, and revision. There were 28 patellar component failures in 24 patients.
      Eighteen patellar components required revision. The average time to failure was
      6.8 years. The average time to revision was 6.3 years. Survivorship analysis
      revealed .9662 survivorship at 5 years, which decreased to .8976 at 10 years, and
      .8641 at 14 years. These results do not compare favorably with the results of
      total knee arthroplasty with all-polyethylene patellar components. The use of
      metal-backed patellar components should be avoided.

PMID- 11451108
TI  - The failure of all-polyethylene patellar components in total knee replacement.
AB  - The patellar component of total knee replacement is the most frequent source of
      nonseptic complications after total knee arthroplasty. The purpose of the current
      study was to review the radiographic factors associated with loosening of all
      polyethylene patellar components. Four thousand five hundred eighty-three cases
      of Anatomic Graduated Components total knee replacements were performed at the
      authors' institution during the past 15 years. Radiographs were reviewed and
      loosening was defined as global radiolucency or component migration. Four
      thousand two hundred eighty-seven allpolyethylene patellar components were
      implanted. There were 180 (4.2%) loose all-polyethylene patellar components. The
      mean time to loosening was 2.6 years (+/- 1.75 years). Fifteen (0.3%) patellar
      components required revision. Five radiographic features were associated with
      failure. The incidence and mean time of appearance were recorded: (number;
      incidence; time) (1) Bone-cement radiolucency, n = 174, 96.7%, 1.4 years; (2)
      increased density, n = 118, 65.6%, 1.8 years; (3) trabecular collapse of the
      bone, n = 160, 88.9%, 2.3 years; (4) patella fracture and fragmentation, n = 133,
      73.9%, 2.5 years; and (5) lateral subluxation of the residual patella bone, n =
      146, 81.1%, 2.9 years. Lateral retinacular release was associated with an
      increased rate of patellar loosening. Loosening of the allpolyethylene patella
      component is an avascular process strongly associated with lateral retinacular
      release and for which the patient infrequently requires revision surgery.

PMID- 11451109
TI  - Total knee arthroplasty with 4.4 mm of tibial polyethylene: 10-year followup.
AB  - A consecutive series of 387, one-piece, 8-mm tibial components were implanted in
      313 patients. All tibial prostheses were manufactured with 4.4 mm of polyethylene
      directly molded to a 3.6 mm cobalt chrome metal baseplate. The average age of the
      patients at surgery was 70.6 years. From this group, a subset of 116 patients
      underwent bilateral total knee arthroplasties with an 8-mm tibial component on
      one side and at least a 10-mm thick tibial component (at least 6.4 mm of
      polyethylene) on the other side. The followup averaged 10.7 years. Postoperative
      knee and pain scores average 81.4 points and 47.2 points, respectively. No
      radiographic polyethylene wear or osteolytic lesions were identified. Tibial
      radiolucencies were observed in four knees. There were nine failures (2.3%).
      Three knees were revised for infection. Five knees were revised for metallosis
      secondary to failure of metal-backed patellas. No loose tibial components were
      identified. Defining failure as revision for any reason or loosening of any
      component, Kaplan-Meier survival rates at 5, 10, and 15 years were 98.7%, 95.4%,
      and 94.3%, respectively. There was no significant difference in clinical scores
      or survival rates between the knee components with thicker (at least 6.4 mm) or
      thinner (4.4 mm) polyethylene.

PMID- 11451110
TI  - Muscle forces and pronation stabilize the lateral ligament deficient elbow.
AB  - The influence of muscle activity and forearm position on the stability of the
      lateral collateral ligament deficient elbow was investigated in vitro, using a
      custom testing apparatus to simulate active and passive elbow flexion. Rotation
      of the ulna relative to the humerus was measured before and after sectioning of
      the joint capsule, and the radial and lateral ulnar collateral ligaments from the
      lateral epicondyle. Gross instability was present after lateral collateral
      ligament transection during passive elbow flexion with the arm in the varus
      orientation. In the vertical orientation during passive elbow flexion, stability
      of the lateral collateral ligament deficient elbow was similar to the intact
      elbow with the forearm held in pronation, but not similar to the intact elbow
      when maintained in supination. This instability with the forearm supinated was
      reduced significantly when simulated active flexion was done. The stabilizing
      effect of muscle activity suggests physical therapy of the lateral collateral
      ligament deficient elbow should focus on active rather than passive mobilization,
      while avoiding shoulder abduction to minimize varus elbow stress. Passive
      mobilization should be done with the forearm maintained in pronation.

PMID- 11451111
TI  - Effect of femoral component offset on polyethylene wear in total hip
      arthroplasty.
AB  - Seventeen staged, bilateral total hip arthroplasties performed in 17 patients
      were reviewed to compare side-to-side polyethylene wear. Implants used on both
      sides were similar except for implant offset: one hip in each patient was
      replaced using a femoral component having a standard implant offset, whereas the
      other side had a lateral offset implant. The mean followup was 5.70 years (range,
      2-10.2 years) on the side with a standard femoral implant and 5.67 years (range,
      2-9.7 years) on the side with a lateralized femoral component. The only
      statistically different parameter between the sides was the femoral component
      offset. All other parameters affecting polyethylene wear, such as period of
      followup, head size, head type, cup size, cup inclination, medialization of cup,
      and patient-related factors were similar on both sides. On the side with a
      standard femoral component, the mean actual prosthetic offset (determined by
      manufacturer's specifications) was 35.2 mm and the radiologic offset was 31.5 mm.
      On the side with a lateralized femoral component, the actual prosthetic offset
      was 42.5 mm and the radiologic offset was 40.1 mm. The difference in offsets
      between the sides was statistically significant. The mean preoperative offset of
      the femur was 38.8 mm. Regression analysis revealed that only femoral component
      offset and cup size correlated significantly with linear wear rate. On the side
      with a standard femoral component, the linear wear rate was 0.21 mm per year,
      whereas on the side with a lateralized femoral component, the linear wear rate
      was 0.10 mm per year. The differences in the linear wear rates were significant.
      Lateralization of the femoral component in this series more closely restored
      preoperative hip biomechanics and significantly decreased polyethylene wear.

PMID- 11451112
TI  - Effect of acetabular cup position and orientation in cemented total hip
      arthroplasty.
AB  - Long-term clinical results of total hip arthroplasty for patients with
      developmental acetabular dysplasia of the hip have been reported, but placement
      of the femoral head center or cup orientation remains controversial, especially
      with a severe anterolateral shallow acetabulum or dislocated femoral head.
      Results of 41 Muller and 34 Harris Design 2 cemented total hip arthroplasties
      were evaluated for developmental dysplasia of the hip. The femoral head center
      and acetabular cup inclination angle were measured from the interteardrop line.
      Linear wear and wear direction were measured using the Livermore technique. The
      best position of the femoral head center was less than 35 mm vertically from the
      interteardrop line and 25 mm laterally from the teardrop. Femoral head center
      analysis showed that hips with the cup in a lateral and superior cup position all
      were revised, but a superior and medial position combined with a cup inclination
      angle less than 40 degrees did not require revision. Hips with a cup inclination
      angle more than 45 degrees had superior and lateral penetration patterns of the
      polyethylene. However, hips with an inclination angle less than 35 degrees and
      medial placement had medial head penetration patterns. With these all
      polyethylene monolithic cemented cups, regardless of the femoral head diameter or
      cup thickness, better long-term results occurred with a cup inclination angle of
      40 degrees or less and medial position of the cup.

PMID- 11451113
TI  - Fistula between a total hip arthroplasty and the rectum: a case report.
AB  - An 81-year-old man was referred to the authors for examination of the
      gastrointestinal tract. A proctoscopy revealed a draining sinus tract in the
      terminal rectum. Plain radiographs revealed a failed total hip arthroplasty that
      had migrated into the pelvis. Hip aspiration revealed an infection with bacteria
      commonly found in the gastrointestinal tract. A fistulogram confirmed a
      connection between the rectum and the hip replacement. The development of a
      fistula between the colon and the hip is extremely uncommon. A fistula between
      the hip and the rectum is a previously unreported complication of total hip
      arthroplasty.

PMID- 11451114
TI  - Relationship between frontal knee alignment and reference axes in the distal
      femur.
AB  - The two transepicondylar axes (the clinical and surgical epicondylar axes), the
      posterior condylar axis, and the anteroposterior axis were constructed using
      computed tomography scans in 111 (66 patients) knees with symptomatic arthritis.
      The relationships between angles made by these reference axes and two angles
      indicating frontal knee alignment (the tibiofemoral valgus angle and the femoral
      valgus angle) were investigated. In Y of the knees, the surgical epicondylar axis
      could not be constructed because the sulcus of the medial epicondyle was not
      recognizable. The condylar twist angle was almost constant and averaged 6 degrees
      when the femoral valgus angle was 9 degrees or less, but increased gradually when
      the angle was greater than 9 degrees. The difference between the condylar twist
      angle and the posterior condylar angle was constantly 3 degrees. The
      anteroposterior axis was almost at right angles to the clinical epicondylar axis,
      and the relationship between these axes was constant, independent of the femoral
      valgus angle. With 3 degrees to 6 degrees external rotation relative to the
      posterior condylar axis, the femoral component could be set parallel to the
      transepicondylar axis in common varus or neutral knees. In cases with a larger
      femoral valgus angle, the anteroposterior axis would be a more reliable reference
      axis. Preoperative computed tomography scans are recommended for patients with
      knees with severe valgus deformity or severe hypertrophic osteoarthritis.

PMID- 11451115
TI  - In vivo three-dimensional knee kinematics using a biplanar image-matching
      technique.
AB  - A biplanar image-matching technique was developed and applied to a study of
      normal knee kinematics in vivo under weightbearing conditions. Three-dimensional
      knee models of six volunteers were constructed using computed tomography.
      Projection images of the models were fitted onto anteroposterior and lateral
      radiographs of the knees at hyperextension and every 15 degrees from 0 degrees to
      120 degrees flexion. Knee motion was reconstructed on the computer. The femur
      showed a medial pivoting motion relative to the tibia during knee flexion, and
      the average range of external rotation associated with flexion was 29.1 degrees .
      The center of the medial femoral condyle translated 3.8 mm anteriorly, whereas
      the center of the lateral femoral condyle translated 17.8 mm posteriorly. This
      rotational motion, with a medially offset center, could be interpreted as a screw
      home motion of the knee around the tibial knee axis and a posterior femoral
      rollback in the sagittal plane. However, the motion of the contact point differed
      from that of the center of the femoral condyle when the knee flexion angle was
      less than 30 degrees. Within this range, medial and lateral contact points
      translated posteriorly, and a posterior femoral rollback occurred. This biplanar
      image-matching technique is useful for investigating knee kinematics in vivo.

PMID- 11451116
TI  - Long-term followup of uncemented tumor endoprostheses for the lower extremity.
AB  - Between 1982 and 1989, 100 primary lower limb reconstructions were done using the
      Kotz Modular Femur Tibia Reconstruction System after resection of a malignant
      tumor. In 32 patients a proximal femur prosthesis was implanted, in 40 patients a
      distal femur prosthesis was implanted, in 19 patients a proximal tibia component
      was implanted, in four patients a total femur prosthesis was implanted, and in
      five patients a total knee prosthesis was implanted. The Kaplan-Meier estimate of
      the overall survival rate of the prostheses was 85% after 3 years, 79% after 5
      years, and 71% after 10 years. The most common reason for implant failure was
      aseptic loosening in 27% of patients (11 patients; range, 10-121 months) after
      the initial operation. The other reasons for revision surgery were implant
      fracture (n 5 4) and infection (n 5 4). Early repair of prostheses-related minor
      complications, such as worn polyethylene bushings, resulted in a statistically
      significant reduction of implant failure. After a median followup of 127.5 months
      after the initial surgery, 51 patients had died and eight patients were lost to
      followup. Forty-one patients were evaluated clinically and radiologically using
      the Musculoskeletal Tumor Society score and the radiologic implant evaluation
      system of the International Symposium on Limb Salvage; these 41 patients had a
      mean of 80% (range, 40%-100%) of the normal functional capability.

PMID- 11451117
TI  - Long-term results of hemipelvis reconstruction with allografts.
AB  - Thirteen patients underwent pelvic reconstruction by massive allografts after
      resection of a malignant tumor (primary in 10 patients and metastatic in three
      patients). In 10 patients, the tumor involved the acetabulum and iliac wing and
      was reconstructed by a hemipelvic allograft; this was accompanied by a hip
      arthroplasty in nine of the patients. In three patients, a femoral metaphyseal
      tumor extending to the acetabulum was reconstructed by a total acetabular
      allograft and a composite proximal femoral allograft prosthesis. Two patients
      (20%) had a local recurrence, and one patient died of massive pulmonary embolism.
      Postoperative complications were one infection and two dislocations. At 3 years,
      one cup loosening and one acetabular fatigue fracture required surgery. The
      functional result was excellent in two patients whose gluteal muscles could be
      spared, good (allowing a normal family life) in six patients, fair in two
      patients, and poor in two patients. Seven patients had a Musculoskeletal Tumor
      Society rating greater than 60% of normal (the mean rating in 12 patients was
      56.4%). No evidence of long-term deterioration was seen in the patients with the
      longest followups (7, 8, 10, and 14 years). Reconstruction of the hemipelvis with
      massive allografts and arthroplasty is a rewarding but demanding procedure and
      should be reserved for physically active patients who are in good general health
      and are expected to have a response to anticancer therapy. The procedure is
      particularly suitable for patients with primary tumors.

PMID- 11451118
TI  - Total condylar knee arthroplasty: a long-term followup.
AB  - Between July 1977 and December 1983, 80 patients underwent 120 arthroplasties
      using a total condylar knee prostheses. Forty-one patients (68 knees) died and 13
      patients were lost to followup. Twenty-six patients with 34 total condylar
      replacements were available for clinical followup. During the followup, 10 knees
      in nine patients (8.3%) from the overall 80 patients (120 knees) underwent
      revision; three (four knees) for aseptic loosening, one for periprosthetic
      fracture, three for infection, and two patients underwent revision for pain.
      Three revisions (three patients) occurred in the group of 26 patients available
      for followup. The average age of this group of patients at followup was 78 years
      (range, 53-94 years). There were 10 men and 16 women. Considering the high mean
      age of the patients in the series and patients' overall health status, the
      clinical results were extremely good. Kaplan-Meier analysis showed a survivorship
      of 91% at 23 years followup, considering revision as an end point. Although there
      have been several changes in total knee replacement designs, materials, and
      implantation techniques, the long-term outcome of the original total condylar
      knee prosthesis is excellent.

PMID- 11451119
TI  - Pigmented villonodular synovitis of the hip: 2- to 23-year followup study.
AB  - Pigmented villonodular synovitis affecting the hip is rare. Seven new patients
      are presented and 117 cases from the literature are reviewed. Among the new
      patients, two refused treatment; in one patient, severe bone loss was observed
      after a radiographic followup of 21 years; the second patient showed no
      radiographic changes 2 years after diagnosis. One patient underwent a synovectomy
      and had a recurrence 9 years later, requiring a total hip replacement. The
      remaining four patients underwent synovectomy and primary total hip replacement
      with no recurrences detected after an average followup of 13 years (range, 2-23
      years). Among 117 cases published, 62 patients (53%) did not have enough
      information for analysis. A metaanalysis using the remaining 55 patients was
      done. In nine patients (16%; nine of 55) the diagnosis was made with a
      preoperative biopsy. Treatment consisted of synovectomy in 26 patients (47%; 26
      of 55), arthroplasty in 24 (43%; 24 of 55), arthrodesis in two (4%; two of 55),
      and hindquarter amputation in a patient misdiagnosed as having synovial sarcoma
      (2%; one of 55). Two patients (4%; two of 55) were not treated. Ten patients had
      a recurrence (19%; 10 of 53); nine in the synovectomy group (35 %; nine of 26)
      and one in the joint replacement group (4%; one of 24). Synovectomy is
      recommended for patients with preserved articular cartilage and total hip
      replacement is recommended for patients with secondary osteoarthritis. Removal of
      all macroscopic tumors including careful curetting of the osteolytic lesions
      should be done as they may constitute a source of recurrence.

PMID- 11451120
TI  - Elastofibroma dorsi as a cause of shoulder pain or snapping scapula.
AB  - Elastofibroma dorsi is a benign soft tissue tumor, not well-known because of its
      low incidence, located in the chest wall in the subscapular area. In 10 patients
      with elastofibroma dorsi, the clinical symptoms were snapping scapula or shoulder
      pain. In three of the patients, the previous diagnosis was shoulder impingement,
      and the patients were treated without success. The clinical diagnosis was
      confirmed by magnetic resonance imaging. Surgical treatment resolved the symptoms
      in all patients. This tumor should be considered in the differential diagnosis of
      snapping scapula or shoulder impingement.

PMID- 11451121
TI  - Type III tibial spine avulsions treated with arthroscopic Acutrak screw
      reattachment.
AB  - Type III fractures of the tibial spine require open reduction and internal
      fixation when conservative treatment fails. The Acutrak cannulated screw system
      has been used successfully for arthroscopic reduction and fixation of these
      injuries. It was used in four children and two adults; all patients have returned
      to their preinjury exercise status. The use of a tent peg technique in children
      allows preservation of the proximal tibial physis, which prevents premature
      epiphysiodesis.

PMID- 11451122
TI  - Fixation strength and pin tract infection of hydroxyapatite-coated tapered pins.
AB  - In a multicenter, prospective, randomized study, the biomechanical and clinical
      properties of the bone-pin interface were compared with standard tapered pins and
      hydroxyapatite-coated tapered pins implanted in patients who underwent femoral
      and tibial external fixation treatments. The results showed that the
      hydroxyapatite-coated tapered pins are clinically effective in improving the
      strength of fixation of the bonepin interface. This improvement corresponded to a
      lower rate of pin tract infection. In the hydroxyapatite-coated pin group, there
      were no differences in strength of fixation between the pins removed from the
      infected and uninfected pin tracts. In this pin group, the mean pin extraction
      torque was 531 +/- 225 Ncm in the infected pin tracts and 508 +/- 233 Ncm in the
      uninfected pin tracts. In the standard pin group, the mean pin extraction torque
      was 73 +/- 142 Ncm in the infected pin tracts and 211 +/- 216 Ncm in the
      uninfected pin tracts. The advantages provided by the hydroxyapatite-coated pins
      were higher in cancellous bone than in cortical bone.

PMID- 11451123
TI  - Biomechanics of calcaneal fractures: a model for the motor vehicle.
AB  - Changes in legislation, availability of passive or active restraint systems, or
      both, together with increased public awareness for safety and the need for use of
      restraint, have shifted the spectrum of trauma in motor vehicle crashes from the
      head and torso to other regions. Lower extremity trauma in motor vehicle crashes
      continues to be a significant problem. The objective of this study was to
      investigate the biomechanics of the human foot and ankle complex under impact
      loading and replicate calcaneal fractures routinely seen in motor vehicle
      crashes. Twenty-two unembalmed cadaver lower extremity specimens were subjected
      to dynamic loads using a minisled pendulum device. Input and output forces and
      results of pathologic analysis were obtained using load cell data, radiographs
      obtained before and after testing, and gross dissection. The intraarticular
      fracture patterns produced were similar to those seen clinically and described in
      the literature. Maximum forces ranged from 3.6 to 11.4 kN for the fracture, and
      0.5 to 7.3 kN for the nonfracture groups. Logistic regression analysis revealed a
      50% probability of calcaneal fracture at 5.5 kN and a 25% probability at 4.0 kN.
      These studies will lead to an understanding of the tolerance of the lower
      extremity in sustaining calcaneal fractures under impact. Implications of the
      work are in the design of crash test dummies, data acquisition, and modifications
      in motor vehicle design and safety.

PMID- 11451124
TI  - Optimum tensioning position for extensor indicis to extensor pollicis longus
      transfer.
AB  - This study evaluates various wrist and thumb positions for tensioning the
      extensor indicis proprius when transferred to the extensor pollicis longus tendon
      to determine which positions provide optimum passive range of flexion and
      extension of the thumb. In five adult cadaver upper limbs, transfer of the
      extensor indicis proprius to the extensor pollicis longus was simulated. The
      limbs were fixed with the elbow in 90 degrees flexion and the forearm and wrist
      in neutral. Surface bone markers were digitized to determine the thumb and wrist
      positions in three-dimensional space and their intersegmental joint angles.
      Twelve combinations of thumb (the interphalangeal and metacarpophalangeal joints)
      and wrist positions for tensioning were tested. A fixed tension of 80 N was
      applied to the tendon ends for each of the tensioning positions and during the
      transfer to ensure that the tendon remained taut. A wrist tenodesis effect was
      used subsequently to assess the passive range of thumb motion as an indicator of
      the outcome of the transfer. The results showed that the better tensioning
      position was with the thumb fully extended and the wrist in neutral. In six
      patients in whom an extensor indicis proprius to extensor pollicis longus
      transfer was done, the tendons were tensioned with the thumb in full extension
      and the wrist in neutral. A prospective review and functional assessment at an
      average of 18.6 months' followup was done. No significant differences between the
      surgically treated and normal thumbs were seen for the Jebsen Taylor, 9-peg, and
      grip and pinch strength tests. The study suggests that in an extensor indicis
      proprius to extensor pollicis longus transfer, tensioning of the tendons with the
      thumb in full extension and the wrist in neutral gives good thumb flexion and
      extension range.

PMID- 11451125
TI  - Effect of gas-plasma sterilization on the osteoinductive capacity of
      demineralized bone matrix.
AB  - The current study evaluated the effect of low-temperature hydrogen peroxide gas
      plasma sterilization on the osteoinductive capability of human demineralized bone
      matrix using a rat model. Twelve athymic rats received three separate implants
      consisting of steam-sterilized demineralized bone matrix (negative control),
      sterile-harvest demineralized bone matrix (positive control), and gas-plasma
      sterilized demineralized bone matrix. A demineralized bone matrix pellet from
      each sterilization group was placed individually into one of three separate soft
      tissue pockets created in the epaxial musculature of each rat. All 12 rats were
      euthanized 9 weeks after implantation. Each implantation site was removed along
      with 0.5-cm normal tissue around the implant. Histologic examination was done on
      each implant site to determine the presence or absence of new bone, cartilage, or
      bone marrow elements. All 12 sterile harvest demineralized bone matrix sites
      histologically contained new bone elements, whereas none of the negative control
      or gas plasma sterilized demineralized bone matrix sites contained any of these
      same elements. The results of this study indicate that demineralized bone matrix
      sterilized with low-temperature, gas-plasma sterilization loses its
      osteoinductive capacity in a manner similar to that of steam-sterilized
      demineralized bone matrix, making low-temperature, gas- plasma sterilization
      unsuitable as a method of secondary sterilization of demineralized bone matrix.

PMID- 11451126
TI  - Effect of early axial dynamization on tibial bone healing: a study in dogs.
AB  - Early axial dynamization and its effect on experimental tibial bone healing was
      compared with healing under rigid fixation in a time-sequenced manner using dogs.
      An external fixator that could be rigidly locked or set to allow free axial
      movement while preventing bending and shear was used. Both tibias were
      osteotomized and externally fixed, leaving a gap between bone ends of 2 mm. At 1
      week, one side was dynamized, whereas the other side was kept rigidly locked as a
      control. Dogs were euthanized at 1 day and 1, 3, 5, 8, and 11 weeks after
      dynamization. The outcome measures were static and dynamic load-bearing,
      periosteal callus development, new bone formation, callus tissue composition, and
      mechanical strength. Load bearing was higher on the dynamized limbs during
      standing for the first 5 weeks and during gait for the first 3 weeks after
      dynamization compared with the controls. Maximum periosteal callus size was
      reached faster and was distributed more symmetrically on the dynamized side. The
      periosteal callus area decreased at 12 weeks on the dynamized sides, but there
      was no significant change in the area on the control sides. Endosteal new bone
      formation and bone density decreased between 9 and 12 weeks only on the dynamized
      sides. The dynamized side showed a significantly higher torsional stiffness at 6
      weeks than did the controls. There were no significant differences between
      dynamized and control tibias at other times. Maximum torque also tended to be
      higher on the dynamized sides at the same time. Early axial dynamization appeared
      to accelerate callus formation and remodeling and to provide higher mechanical
      stiffness during early stages of bone healing.

PMID- 11451127
TI  - A new model for the action of the middle deltoid.

PMID- 11451128
TI  - Does modularity affect clinical success? A comparison with a minimum 10-year
      followup.
AB  - A comparison of the clinical and radiographic results of patients with metal
      backed monoblock Insall-Burstein I and modular Insall-Burstein II Posterior
      Stabilized Knee Prostheses was done. The minimum followup was 10 years. The
      clinical results were comparable with a similar average Hospital for Special
      Surgery knee score of 85 and 84 points, respectively. Likewise, the Knee Society
      Knee and Functional Scores showed no statistical difference. Radiographically,
      the incidence of minor radiolucent lines was 11% for the Insall-Burstein I
      prostheses and 29% for the Insall-Burstein II prostheses, but their presence was
      of no clinical significance. There was no clinical or radiographic evidence of
      tibial component loosening with either prosthetic design and there were no
      revisions for polyethylene wear or osteolysis in either cohort of patients.

PMID- 11451129
TI  - Total condylar knee replacement: preliminary report. 1976.

PMID- 11451130
TI  - Total knee arthroplasty using cruciate-retaining kinematic condylar prosthesis.
AB  - The purpose of the current study was to evaluate the long-term results of the
      Kinematic I condylar prosthesis with retention of the posterior cruciate
      ligament. One hundred sixty-eight total knee arthroplasties in 118 patients (mean
      age, 65.2 years; range, 21-88 years) were inserted with cement, an all
      polyethylene patella, metal-backed tibia, and posterior cruciate ligament
      retention. Sixty-one patients (86 knees) died, one patient had an above-knee
      amputation, and three patients (five knees) were lost to followup; therefore, 66
      knees (excluding revisions) in 50 patients were available for followup at a mean
      of 15.7 +/- 1.1 years (range, 14-20 years). Of the entire cohort of 168 knees, 13
      have been revised: one for medial femoral condyle fracture, one for tibiofemoral
      instability, one for femoral and two for tibial component aseptic loosening, four
      for tibial polyethylene wear, and four for patellar component aseptic loosening.
      The 15-year survivorship free of any component revision excluding infections was
      88.7% (confidence interval, 82%-95%). The 15-year survivorship free of
      radiographic loosening and/or revision of any component was 85.1% (confidence
      interval, 78%-92%). The current study shows good function and survivorship of the
      posterior cruciate-sparing Kinematic I condylar prosthesis at a mean of 15.7 +/-
      1.1 years.

PMID- 11451131
TI  - Twenty-year evaluation of meniscal bearing and rotating platform knee
      replacements.
AB  - Clinical results of the initial cemented and cementless series of 373 New Jersey
      Low Contact Stress total knee replacements in 282 patients surviving at least 10
      years were analyzed using a strict knee scoring scale. The study showed
      excellent, good, fair, or poor results in 68.1%, 29.8%, 2.1%, or 0% of primary
      posterior cruciate-retaining meniscal bearing knee replacements, 46.7%, 53.3%,
      0%, or 0% results in primary cemented rotating platform knee replacements, and
      68.1%, 29.8%, 2.1%, or 0% results in primary cementless rotating platform knee
      replacements, respectively. Radiographic evaluation at minimum 10-year followup
      showed stable fixation of all components, no gross migration but significant
      osteolysis requiring bearing exchange and bone grafting in three cementless
      rotating platform knee replacements (1.8%) in three patients who underwent
      previous surgeries at an average of 10.2 years from the index surgery.
      Survivorship of the patients who underwent primary cementless posterior cruciate
      retaining meniscal bearing knee replacements with an end point of revision for
      any mechanical reason was 97.4% at 10 years and 83% at 16 years; using an end
      point of a poor clinical knee score the survivorship was 98.9% at 10 years and at
      16 years. Survivorship of the patients who underwent primary cemented rotating
      platform knee replacements with end points of revision for any mechanical reason
      or a poor clinical knee score was 97.7% at 10 years and at 20 years. Survivorship
      of the patients who underwent cementless rotating platform knee replacements with
      end points of revision for any mechanical reason or a poor clinical knee score
      was 98.3% at 10 years and at 18 years.

PMID- 11451132
TI  - Long-term followup of anatomic graduated components posterior cruciate-retaining
      total knee replacement.
AB  - The purpose of the current study was to evaluate the authors' 15-year experience
      with the Anatomic Graduated Components total knee replacement. This is a report
      of the survivorship of 4583 Anatomic Graduated Component total knee
      arthroplasties. Kaplan-Meier survival analyses were performed with the end point
      defined as radiographic loosening, revision, or both. This end point was
      subdivided into the best case scenario in which it was assumed that all the
      patients lost to followup were doing well throughout the study and a worst case
      scenario in which it was assumed that all patients lost to followup had failed
      results at their last clinic visit. There were six (0.18%) femoral, 21 (0.46%)
      tibial, and 180 (4.2%) all-polyethylene patellar component failures secondary to
      aseptic loosening. All femoral components and 90% of the tibial components were
      revised; however, only 15 patellar components were revised. The clinical survival
      rate with revision of one or more of the components was 98.86% at 15 years.
      Despite having nearly flat-on-flat geometry and retaining the posterior cruciate
      ligament, which should increase the stresses in the polyethylene and at the bone
      cement interface, this total knee replacement has proved to have minimal wear and
      excellent longevity with time. The authors think this is a result of the direct
      compression molded polyethylene articulation and the nonmodular configuration
      that incorporates metal backing on the tibial component and eliminates back-sided
      tibial component polyethylene wear.

PMID- 11451133
TI  - Long-term followup of the Miller-Galante total knee replacement.
AB  - One hundred seventy-two consecutive cemented Miller-Galante-I total knee
      arthroplasties in 155 patients were compared with 109 consecutive cemented Miller
      Galante-II total knee arthroplasties in 92 patients. The average followup was 11
      years (range, 8-15 years) and 9 years (range, 8-10 years), respectively. Of the
      172 Miller-Galante-I arthroplasties, there have been 21 revisions; 15 patellar
      revisions; two included femoral revisions attributable to abrasion. Six
      additional well-fixed femoral and tibial components were revised: two for early
      instability, one for pain, one for periprosthetic fracture, and two for
      infection. No component had aseptic loosening or osteolysis. Using revision or
      loosening of any components as the end point, the Kaplan-Meier 10-year
      survivorship was 84.1% +/- 4.1%. Of the 109 Miller-Galante-II arthroplasties,
      there have been no component revisions, no aseptic loosening, and no osteolysis.
      Using revision or loosening of any components as the end point, the Kaplan-Meier
      10-year survivorship was 100%. The Miller-Galante knee systems showed excellent
      fixation with no loosening and no osteolysis at as many as 15 years.
      Additionally, there have been no component revisions for late instability at as
      many as 15 years. Finally, the high prevalence of patellofemoral complications
      with the Miller-Galante-I design has been obviated with the Miller-Galante-II
      design.

PMID- 11451134
TI  - Long-term followup of cementless versus hybrid fixation for total knee
      arthroplasty.
AB  - In a prospective trial, 99 patients (100 knees) with osteoarthritis were
      randomized to either cementless or hybrid fixation of cruciate-retaining Miller
      Galante-I total knee arthroplasties between January 1987 and December 1988.
      Thirty-one patients died during the study period and two additional patients were
      lost to followup, leaving 67 total knee arthroplasties for analysis. Thirty-nine
      patients underwent revision surgery at an average of 6.9 years postoperatively.
      The main reason for revision surgery was failure of metal-backed patellas with 25
      knees revised at an average of 7.4 years, and the second most common reason was
      tibial polyethylene failure. Survival curves showed 60% survival at 14 years for
      all knees, and 85% survival at 14 years when failures for metal-backed patellas
      and infection were excluded, with no significant difference between the two
      groups. Failure of metal-backed patellas was significantly higher in the
      cementless group. Tibial polyethylene failure occurred in five of the hybrid
      group and none of the cementless group, but this was not a significant
      difference. Surviving prostheses were assessed at an average of 12.8 years
      (range, 11.5-13.5 years). Average clinical scores were 94.8 points
      preoperatively, and 143 points at the latest followup, with significantly higher
      scores in the hybrid group. Differences in outcome between the two groups were
      not sufficiently significant to recommend one method of fixation over another.
      With elimination of poor design features related to the patellofemoral
      articulation and thin tibial polyethylene, cruciate-retaining total knee
      arthroplasties can yield good durable results, whether cementless or hybrid
      fixation is used.

PMID- 11451135
TI  - Overview: long-term followup: predicting the success of a total knee
      arthroplasty.
AB  - As the number of total knee arthroplasties performed each year in the United
      States continues to increase, knowledge of long-term prosthetic performance and
      implant durability is paramount. A selection of the best total knee replacement
      system for a given patient should be based on long-term followup studies
      reviewing, among other parameters, survivorship and complications. The importance
      of such long-term data should not be underestimated.

PMID- 11451136
TI  - Long-term followup of the bone-ingrowth Ortholoc knee system without a metal
      backed patella.
AB  - Between June 1981 and January 1984, 265 Ortholoc-I femoral and tibial components
      were implanted using bone-ingrowth technique in 202 patients. Five knees (five
      patients) were lost to followup and 66 knees were excluded because the patients
      died, leaving 184 knees (165 patients) with 15 to 18 years followup. One knee
      loosened during the 15- to 18-year followup period and was revised, and five
      knees were revised for infection. Survival rate at 18 years considering loosening
      was 98.6%. At 15 years after surgery, 79.9% of patients did not have pain, 10.1%
      had mild pain, 8% had moderate pain, and 2% had severe pain. At 18 years after
      surgery, 77.6% did not have pain, 7.2% had mild pain, 5.2% had moderate pain, and
      1% had severe pain. Knee flexion was 110 degrees preoperatively and increased to
      a mean of 115 degrees at 2 years postoperative, then remained unchanged for the
      rest of the followup. Intramedullary alignment proved to be highly effective, and
      has become the standard for total knee arthroplasty instrumentation systems.
      Total knee replacement with bone-ingrowth technique was a reliable and effective
      means of treating the end-stage arthritic knee. In patients who required revision
      surgery, excellent bone stock remained and revision with bone-ingrowth technique
      was accomplished easily.

PMID- 11451137
TI  - Ten- to 14-year clinical followup of the cementless Natural Knee system.
AB  - Of 300 consecutive knees (238 patients) that had undergone arthroplasty with the
      cementless Natural Knee prosthesis from 1985 to 1989, 176 knees (141 patients)
      were available for followup at an average of 12 +/- 1 years after the operation.
      Knee function was improved significantly. Modified Hospital for Special Surgery
      knee scores improved from 59.1 +/- 13.2 points preoperatively to 97.8 +/- 4.7
      points at last followup. At last followup, knee range of motion averaged 0
      degrees +/- 2 degrees to 120 degrees +/- 10 degrees. Implant survival was 93.4%
      (including infection and simple polyethylene exchanges) and 95.1% (excluding
      infection and simple polyethylene exchanges) at 10 years when applying the Kaplan
      Meier survival analysis, using loose components, revision, or both as failure
      criteria. Besides the three revisions for infection, only two femoral and one
      tibial component required revision. The patellar component survivorship at 10
      years was 95.1%. All patellar revisions were attributed to edge wear. Subsequent
      operative and design changes, including patellar component medialization and
      countersinking, have decreased the incidence of patellar revision. The long-term
      results of this cementless knee system compare favorably with those of cemented
      systems. The Natural Knee design has provided excellent and predictable long-term
      clinical results in the current series of active patients.

PMID- 11451138
TI  - The Genesis total knee prosthesis: a 10-year followup study.
AB  - This current author reports on the results of 100 consecutive patients with
      osteoarthritis who underwent a primary cemented total knee replacement using the
      Genesis prosthesis and who have been followed up for at least 10 years after
      surgery. In patients in whom the posterior cruciate ligament was sacrificed
      (combined flexion and angular deformities > 15 degrees to 20 degrees) a posterior
      stabilized cam module was affixed to the femoral component and a posterior
      stabilized polyethylene was used. More than 95% of patients in both groups had
      excellent pain relief. The mean flexion was 114 degrees in the group of patients
      in whom the posterior cruciate ligament was sacrificed and 117 degrees in the
      group of patients in whom the posterior cruciate ligament was retained. Partial
      bone cement tibial radiolucencies were seen in 12% of the patients in whom the
      posterior cruciate ligament was retained and 2% of the patients in whom the
      posterior cruciate ligament was sacrificed. At 10 years, 76% of the group in whom
      the posterior cruciate ligament was retained had excellent results and 20% had
      good results. In the group in whom the posterior cruciate ligament was sacrificed
      75% had excellent results and 23% had good results. The survivorship was 96% in
      the group of patients in whom the posterior cruciate ligament was retained and
      97% in the group of patients in whom the posterior cruciate ligament was
      sacrificed.

PMID- 11451139
TI  - Effect of somatostatin on cholecystokinin-induced amylase release in rat
      pancreatic acini.
AB  - The effect of somatostatin on cholecystokinin-induced amylase release was
      investigated in isolated rat pancreatic acini. Acini were isolated by enzymatic
      digestion and incubated in a HEPES buffered Ringer's solution with testing
      reagents for 30 minutes at 37 degrees C. The activity of released amylase, cAMP,
      and inositol phosphate formation were measured. Intracellular calcium
      concentration ([Ca2+]i) was also checked. Somatostatin 14 and octreotide, a
      somatostatin analog, inhibited CCK-stimulated amylase release in a concentration
      dependent manner. The inhibitory effect of octreotide on CCK-induced amylase
      release was not shown when the acini were treated with 8-Br-cAMP, irrespective of
      the presence of IBMX. Forskolin potentiated CCK-induced amylase release and this
      effect was blocked by octreotide treatment; although CCK-8 (3 x 10(-11) M) failed
      to stimulate cAMP formation, octreotide significantly inhibited basal cAMP
      formation in the acini. The increase of [Ca2+]i in response to CCK was inhibited
      by octreotide. However, CCK-induced inositol phosphate formation was not changed
      by 10(-9) M octreotide. Octreotide had no effect on CCK-stimulated tyrosine
      phosphorylation, and tyrosine phosphatase inhibitors (NaF and Na2WO4) did not
      influence the effect of octreotide on CCK-induced amylase release. From these
      results, we conclude that octreotide inhibits CCK-induced amylase release by
      inhibiting basal cAMP formation and decreasing the [Ca2+]i stimulated by CCK.

PMID- 11451140
TI  - Acinar cell carcinoma of the pancreas successfully treated by en bloc resection
      and intraperitoneal chemotherapy for peritoneal relapse: a case report of a 15
      year survivor.

PMID- 11451141
TI  - Increased number of Na+/K+ ATPase enzyme units in Ob/Ob-mouse pancreatic islets.

PMID- 11451142
TI  - Intraductal papillary-mucinous tumor of the pancreas: a historical review of the
      nomenclature and recent controversy.
AB  - A number of studies on mucin-producing cystic neoplasm of the pancreas have been
      reported since the first report of the tumor in 1982. There has been some
      controversy about nomenclatures and clinicopathologic entities of mucin-producing
      cystic tumor, mucinous cystic tumor, and intraductal papillary tumor of the
      pancreas. In 1996 and 1997, new classifications of pancreatic neoplasms were
      published by the World Health Organization (WHO) and Armed Forces Institute of
      Pathology (AFIP). According to the new WHO and AFIP classifications, mucin
      producing cystic neoplasm of the pancreas corresponds mainly to intraductal
      papillary-mucinous tumor and mucinous cystic tumor of the pancreas. and these two
      diseases are independent conditions. Intraductal papillary-mucinous tumor is
      regarded as a unique clinical entity, but controversy remains about the term and
      clinicopathologic entity. Some confusion and problems remain betweeen the two
      lesions. In this review, we review their historical background, terminology, WHO
      and AFIP classification, and problems with classification.

PMID- 11451143
TI  - Pancreatic pseudocysts complicated by splenic parenchymal involvement: results of
      operative and percutaneous management.
AB  - Pancreatic pseudocysts are a common finding in acute and chronic pancreatitis,
      but most are small and uncomplicated, and do not require treatment. Pseudocysts
      with splenic parenchymal involvement are uncommon but have the potential for
      massive hemorrhage. Data on the clinical presentation and optimal treatment of
      this unusual complication of pseudocysts are lacking. The purpose of this review
      was to identify the clinical features of pancreatic pseudocysts complicated by
      splenic parenchymal involvement and to determine the outcome with nonoperative
      and operative therapy. METHODS: A retrospective review of the medical records of
      all patients with pancreatic pseudocysts from December 1984 to January 1999
      revealed 238 patients, of whom 14 (6%) had splenic parenchymal involvement. These
      medical records were reviewed in detail and all pertinent radiographs were
      reviewed by the authors to confirm splenic parenchymal involvement by a
      pancreatic pseudocyst. RESULTS: Initial treatment included observation (n = 2),
      percutaneous drainage (n = 8), and surgery (n = 4). Of the eight patients treated
      by percutaneous drainage, one died, three required repeated percutaneous
      drainage, and three required surgical intervention. None of the patients treated
      primarily by surgery required additional therapy for the pseudocyst. Overall, 11
      patients had complications of the primary therapy, and 25% of patients treated by
      surgery had significant hemorrhage. Complications included infection (n = 5),
      pseudocyst persistence (n = 4), bleeding (n = 2), multisystem organ failure (n =
      2), gastric outlet obstruction (n = 1), and splenic rupture (n = 2). CONCLUSIONS:
      Pancreatic pseudocysts complicated by splenic parenchymal involvement may have
      life-threatening clinical presentations and respond poorly to percutaneous
      drainage. Distal pancreatectomy and splenectomy are effective, but the
      complication rate is high.

PMID- 11451144
TI  - Endoscopic ultrasound in the evaluation and treatment of chronic pancreatitis.
AB  - Endoscopic ultrasound (EUS) was developed in the 1970s specifically for the
      purpose of improved imaging of the pancreas. The close proximity of the pancreas
      to the gastric and duodenal lumen allows EUS to obtain high-resolution images,
      unobstructed by overlying bowel gas. EUS has fewer complications than endoscopic
      retrograde cholangiopancreatography (ERCP) and can detect features of chronic
      pancreatitis (CP) in the pancreatic parenchyma and duct that are not visible to
      any other imaging modality. Because of this high sensitivity, questions have
      arisen whether EUS is oversensitive, especially to ''early" CP. Without a
      definitive gold standard against which to measure EUS (or ERCP and function
      testing), it is currently not possible to know the true accuracy of these
      modalities for early CP. There is now an extensive body of literature suggesting
      that these early changes detected by EUS correlate with histologic changes of CP,
      and may predict response to pancreatic therapy. EUS is uniquely suited to
      performing endoscopic cyst drainage for pancreatic pseudocysts and for
      controlling the pain of CP by EUS-directed celiac plexus block. For endoscopic
      cystenterostomy, EUS allows the endoscopist to localize the cyst, determine if
      the cyst is drainable, and guide a needle and stent into the cyst in a single
      step. Several major questions remain. Can EUS features of CP guide other forms of
      therapy for CP such as enzyme replacement, sphincter of Oddi therapy, and stent
      therapy? Can the detection of early CP by EUS, and subsequent therapy, delay or
      prevent the onset of more severe CP? Can EUS detect early forms for dysplasia and
      malignancy in patients who are at high risk for pancreatic carcinoma? Do changes
      of "early" CP detected by EUS progress to more classic changes (calicification)
      over time?

PMID- 11451145
TI  - Pacinian corpuscle in the human pancreas.
AB  - During our systematic examination of the distribution of cytochrome P450 enzymes
      in the normal and diseased human pancreas, we observed a Pacinian corpuscle in a
      serial section of a tissue from a pancreatic cancer patient. We report the
      histologic and immunohistochemical patterns in this corpuscle and review the
      literature. The Pacinian corpuscle was situated within the pancreas of a 76-year
      old woman with cancer in the head of the pancreas. We could demonstrate
      immunoreactivity within the corpuscle for the neurofilament protein. neuron
      specific enolase, S-100 Protein, and for four cytochrome P450-isozymes. The
      possible function of Pacinian corpuscles in the mammalian and human pancreas is
      discussed.

PMID- 11451146
TI  - Neuroinsular complex type I: morphology and frequency in lean and genetically
      obese mice.
AB  - No quantitative data are available regarding the rate of occurrence of nerve
      cells in association with endocrine pancreas (i.e.. neuroinsular complexes type I
      [NICs]), or the difference in the distribution of NICs in normal and diabetic
      pancreas. In this report, pancreata from 20-day, 7-week, and 9-month-old lean
      (Umea +/?) and obese (Umea ob/ob) mice, as well as 10-month-old C57BL/6JBom and
      Umea ob/ob mice, were analyzed with regard to the association of
      acetylcholinesterase (AChE)-positive and protein gene product 9.5-like (PGP-LI)
      immunoreactive perikarya with islets, and not in association with islets. NIC
      profiles were regularly observed, but were more frequent in the 20-day-old mice
      than in the 9-month-old +/? and ob/ob mice. The NIC profiles were often located
      close to a duct or blood vessel, significantly more frequently than islet
      profiles in general. The data did not reveal any gross abnormality in ob/ob mice
      as regards the frequency of NICs or the number of AChE-positive and PGP-LI
      perikarya. However, the 9-month-old ob/ob mice demonstrated smaller clusters of
      perikarya in their NIC profiles as compared to the other mice, probably
      reflecting the fact that the perikarya were more widely spread out in the
      hyperplastic islets of adult ob/ob mice. The results show that NICs are common
      and represent a substantial proportion of the islets in mouse pancreas,
      supporting the idea that they play a role in islet physiology.

PMID- 11451147
TI  - Isolation, long-term culture, and characterization of rat pancreatic
      fibroblastoid/stellate cells.
AB  - Investigation of pancreatic interstitial fibroblasts has proven difficult in
      situ. We have established a method for the isolation of pancreatic
      fibroblastoid/stellate cells by outgrowth from pancreatic tissue explanted into
      culture dishes. This technique gives a high yield of viable cells from small
      tissue samples. Outgrown fibroblastoid cells were established as a primary cell
      line and characterized during long-term culture. We investigated the development
      of stellate cell markers, i.e. fat storage, expression of desmin, and alpha
      smooth muscle actin (alphaSMA), over weeks in culture. AlphaSMA, investigated by
      indirect immunofluorescence staining and Western blot analysis, revealed a
      constant rise in expression during routine culture. After 13 passages.
      approximately 100% of cells were positive for alphaSMA expression, indicating a
      myofibroblast type of differentiation in vitro.

PMID- 11451148
TI  - Opsonin receptor expression on peritoneal exudative and circulatory neutrophils
      in murine acute pancreatitis.
AB  - Acute severe (necrotizing) pancreatitis is often associated with pancreatic or
      peripancreatic infection. Decreased bacterial clearance due to impaired immune
      defense may cause local infection. We investigated expressions of surface opsonin
      receptors (CD11b, complement receptor 3; CD32/CD16, immunoglobulin G Fc receptor)
      on local and circulatory neutrophils, in murine acute pancreatitis. The mild and
      severe forms of acute pancreatitis were induced by seven and 13 subcutaneous
      injections of caerulein, respectively. Peritoneal exudative and circulatory
      neutrophils were counted and assayed for receptor expressions by flow cytometry,
      serially at 1-72 hours after pancreatitis induction. Histologically, mild and
      severe forms showed edematous and necrotizing pancreatitis, respectively. The
      peritoneal exudative neutrophil count was greater in mild than in severe
      pancreatitis. Expressions of CD11b and CD32/CD16 on local neutrophils were
      upregulated early in mild pancreatitis. This upregulation was attenuated in
      severe pancreatitis. The circulatory neutrophil count was elevated in severe
      pancreatitis but was unchanged in mild pancreatitis. Opsonin receptor expression
      on circulatory neutrophils showed a transient, modest upregulation in the early
      phase of mild pancreatitis. Receptor-positive circulatory neutrophils showed a
      marked elevation that persisted throughout the course of severe pancreatitis. In
      conclusion, severe (necrotizing) pancreatitis is associated with reduced opsonin
      receptor expression on local neutrophils and enhanced expression on circulatory
      neutrophils, as compared with mild (edematous) pancreatitis. These changes may
      contribute to local infectious complications and multiple organ failure, in
      severe pancreatitis.

PMID- 11451149
TI  - Increased islet viability by addition of beraprost sodium to collagenase
      solution.
AB  - The digestion of pancreatic tissue with collagenase is an essential part of the
      islet isolation procedure. However, the process exposes islets to various types
      of harmful factors, including collagenase contaminants, enzymes released from the
      acinar cells, warm ischemia, and mechanical agitation. Nitrogen oxide production
      and cytokine release may also contribute to islet cell damage. Protection of
      islets from such damage would improve the islet yield, survival, and function.
      Beraprost sodium (BPS) is a prostaglandin I2 analogue, is stable in aqueous
      solution, and has a cytoprotective effect on various types of cells. BPS has been
      shown to improve the yield and function of cryopreserved and/or cultured islets.
      These findings prompted us to examine its cytoprotective effect on islets during
      the islet isolation process. Canine islets were isolated by means of a two-step
      digestion method and purified on Euro-Ficoll density gradient solutions (the
      procedure used for human islets). BPS at a concentration of 100 nM was added to
      the collagenase solution. After purification, the islet yield was 434,561 +/-
      35.691 islet number expressed as 150 microm equivalent size (IEQ)/pancreas or
      8,799 +/- 345 IEQ/g of pancreas in the BPS group and 349,987 +/- 52,887
      IEQ/pancreas or 7,998 +/-1610 IEQ/g of pancreas in the control group (n = 8,
      each). The percent viability was 88.5 +/- 0.7% in the BPS group and 82.0 +/-0.9%
      in the control group (P < 0.01). Therefore, the recovery of viable islets
      (calculated by islet number x % viability) was 384,586 +/- 46,804 IEQ/pancreas
      (7,743 IEQ/g) in the BPS group and 286,989 +/- 43,367 IEQ/pancreas (6,558 IEQ/g)
      in the control group (P < 0.02). After culture, significantly higher numbers of
      islets were also recovered in the BPS group than in the control group. The islet
      insulin content was significantly higher in the BPS group than controls (237.8 +/
      38.5 versus 92.3 +/- 25.6 microU/IEQ; P < 0.02), although islets of both groups
      responded with high stimulation indices (>6). These results indicate that the
      addition of BPS to the collagenase solution increases the recovery of viable
      islets, and improves beta cell function.

PMID- 11451150
TI  - Evidence of pituitary adenylate cyclase activating polypeptide (PACAP) in
      pancreatic islet cells by confocal microscopy.
AB  - Several studies have shown that pituitary adenylate cyclase activating
      polypeptide (PACAP) stimulates at very low concentration insulin release from
      pancreatic beta cells. In addition, PACAP has been evidenced in pancreatic
      nervous fibers surrounding the islets, the core of the islet, and the
      capillaries. The aim of the present study was to demonstrate internalization of
      PACAP in pancreatic islet cells. Pancreatic islets were obtained from Wistar rat
      pancreata by modified Lacy's isolation method. The isolated islets were incubated
      in the presence of Fluo-PACAP 27, a fluorescent ligand specific for PACAP
      receptors. At the end of incubation the islets were fixed in paraformaldehyde and
      then observed by confocal microscope. Fluo-PACAP 27 was internalized into
      pancreatic islet cells, and this process was time- and temperature-dependent (37
      degrees C). The fluorescent molecules converged toward the nucleus where an
      intense fluorescence was evidenced after 60 minutes. Incubation with phenyl
      arsine oxide as well as with PACAP 6-38, a receptor antagonist, prevented the
      internalization process. Further studies are required to explain the
      internalization process of PACAP 27 into the nucleus of pancreatic islet cells.

PMID- 11451151
TI  - Pancreatic adenocarcinoma cell lines show variable susceptibility to TRAIL
      mediated cell death.
AB  - BACKGROUND AND AIMS: Programmed cell death via the Fas receptor/Fas Ligand and
      DR4, DR5/TRAIL plays a major role in tumor escape and elimination mechanisms. It
      also promises to be an effective therapy alternative for aggressive tumors, as
      has been recently shown for colon, breast, and lung cancer cells. We attempted to
      clarify the role of these molecules in aggressivity of pancreatic carcinomas and
      to identify possible pathways as targets for therapy. METHODS: Five pancreatic
      cell lines were investigated for the expression of FasL/Fas, DcR3, DR4,
      DR5/TRAIL, DcR1, DcR2, and other death pathways related molecules such as Bax,
      bcl-xL, bcl-2, FADD, and caspase-3 by flow cytometry, immunoblotting, and RT/PCR,
      both semiquantitative and real time (TaqMan). The susceptibility of these cell
      lines to apoptosis mediated by recombinant TRAIL was investigated. The effect of
      therapeutic agents (gemcitabine) on their susceptibility to TRAIL induced
      apoptosis was studied as well. RESULTS: Pancreatic adenocarcinomas expressed high
      levels of apoptosis-inducing receptors and ligands. They showed differential
      susceptibility to cell death induced by TRAIL, despite expressing intact
      receptors and signaling machineries. Treatment with commonly used therapeutic
      agents did not augment their susceptibility to apoptosis. This could be explained
      by the fact that they expressed differentially high levels of decoy receptors, as
      well as molecules known as inhibitors of apoptosis. CONCLUSIONS: The data suggest
      that pancreatic carcinoma cells have developed different mechanisms to evade the
      immune system. One is the expression of nonfunctional receptors, decoy receptors,
      and molecules that block cell death, such as bcl2 and bcl-xL. The second is the
      expression of apoptosis-inducing ligands, such as TRAIL, that could induce cell
      death of immune cells. The success in treating malignant tumors by recombinant
      TRAIL might apply to some but not all pancreatic tumors because of their
      differential resistance to TRAIL-induced cell death.

PMID- 11451152
TI  - Anti-ICAM-1 antibody modulates late onset of acinar cell apoptosis and early
      necrosis in taurocholate-induced experimental acute pancreatitis.
AB  - The hallmark of severe acute pancreatitis (SAP) is massive acinar cell death by
      necrosis. However, programmed, apoptotic acinar cell death has also been
      observed. Little is known about the dynamics, localization, and inductive factors
      of acinar cell apoptosis in SAP. We therefore induced SAP in rats by retrograde
      infusion of 3% sodium taurocholate. Starting as early as 5 minutes after
      taurocholate administration, small scattered groups of acinar cells showed
      zymogen degranulation, loss of cell polarity, cytoplasmic microvacuolization, and
      nuclear shrinkage, but no DNA degradation, thus featuring necrosis. The areas of
      necrotic acini extended at later time points giving rise to larger areas of
      complete parenchymal breakdown after 6 hours. Parenchymal degradation was
      paralleled by neutrophil infiltration and significant tumor necrosis factor (TNF)
      alpha mRNA up-regulation. Up to the 12-hour interval, apoptotic acinar cells
      detected by TUNEL were as rare as in healthy pancreata. At 24 hours, however, the
      acinar apoptotic rate in nonnecrotic parenchyma had dramatically increased.
      Pretreatment of rats with anti-ICAM-1 antibody prior to pancreatitis induction
      led to a significant reduction of neutrophil infiltration along with decreased
      TNF-alpha mRNA expression throughout the 24-hour observation period without
      affecting the presence and dynamics of necrosis. However, anti-ICAM-1
      pretreatment decreased the extent of acinar cell damage by necrosis and
      extensively suppressed acinar cell apoptosis. We conclude that taurocholate
      induces two sequential patterns of acinar cell death in terms of very early
      necrosis followed by late apoptosis during the postacute phase of SAP. The
      progression of necrosis and the late apoptotic acinar cell death seem to be
      influenced by the local presence of neutrophils via a TNF-alpha-dependent
      mechanism. In addition to augmenting necrosis, neutrophils might have an
      apoptosis-inducing potential in SAP.

PMID- 11451153
TI  - Susceptibility to cerulein-induced pancreatitis in inducible nitric oxide
      synthase-deficient mice.
AB  - Production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has
      been proposed as a pathogenic factor in acute pancreatitis, but its role has
      still not been fully examined. The present study explored the role of iNOS in
      cerulein-induced acute pancreatitis using iNOS-deficient mice. Twelve- to 14-week
      old male mice (C57B1/6 and iNOS-deficient) were administered cerulein by
      intraperitoneal (i.p.) injection at hourly intervals for 7 hours and killed 24
      hours later after the first dose. Pancreatic wet weight, pancreatic
      myeloperoxidase (MPO) activity, and levels of plasma nitrite and serum amylase
      were measured. In another experiment isosorbide dinitrate (an NO donor) was given
      by oral gavage every 6 hours for 24 hours beginning simultaneously with cerulein
      injections in iNOS-deficient mice. Cerulein administration dose-dependently
      increased pancreatic wet weight, myeloperoxidase activity, and levels of nitrite
      and amylase in C57B1/6 mice. These parameters (except nitrite levels) were
      significantly intensified in iNOS-deficient mice. At the dose employed, cerulein
      failed to increase nitrite levels in iNOS-deficient mice. The susceptibility to
      cerulein toxicity in iNOS-deficient mice was abolished by NO donor treatment. NO
      release from an iNOS source appears to play a protective role in cerulein-induced
      pancreatitis. At least in part, NO may prevent neutrophil accumulation after
      cerulein administration.

PMID- 11451154
TI  - The method of administration of cholecystokinin determines the effects evoked in
      the pancreas.
AB  - Earlier studies have shown different effects on cell proliferation and weight
      characteristics by sulfated cholecystokinin-8 (CCK-8S) in the rat pancreas when
      the peptide has been administered continuously rather than intermittently. The
      aim of this study was as follows: (i) to compare the effect of continuous
      infusion and of intermittent injections of CCK-8S on cell proliferation, weight
      gain, and induction of apoptosis and (ii) to examine the effect of injections of
      CCK-8S on CCK-A receptor gene expression in the rat pancreas. Male Sprague-Dawley
      rats had subcutaneous continuous infusion of CCK-8S in a dose of 5 microg/kg/h or
      1% bovine serum albumin (BSA) (vehicle) by implanted osmotic minipumps. The rats
      were killed after 4 days. Other rats were either injected subcutaneously only
      once or injected twice daily for 3 days with either 6 microg of CCK dissolved in
      0.5 mL BSA or 0.5 mL BSA alone. The rats were killed 1, 3, 6, and 12 hours after
      the last injection. One hour before death they received 5-bromo-2-deoxyuridine
      (BrdU) intraperitoneally to localize and quantitate the cell proliferation.
      Plasma was collected for analysis of CCK. The pancreas was dissected and
      immunohistochemistry was performed for analysis of the expression of the
      apoptosis promoting protein bax and the apoptosis inhibiting protein bcl-2, and
      for BrdU and CCK-A receptor localization. In situ hybridization (ISH) was used
      for examination and semiquantification of CCK-A receptor mRNA expression.
      Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40%
      increase in pancreatic weight without any effect on BrdU labeling.
      Immunohistochemistry revealed decreased tissue expression of bax but unaffected
      expression of bcl-2. Intermittent injections of CCK-8S led to hyper-CCK-emia with
      increased incorporation of BrdU, indicating increased cell proliferation but no
      increase in pancreatic weight. Immunohistochemistry showed increased expression
      of bax, whereas bcl-2 remained unchanged. Immunofluorescence and ISH for the CCK
      A receptor and its gene expression, respectively, showed a lowest intensity at 3
      hours after CCK-8S injections. The results indicate that decreased apoptosis
      could explain the increased pancreatic weight during continuous infusion of CCK
      8S. An increased apoptosis could explain the lack of pancreatic weight gain upon
      intermittent injections of CCK-8S despite the stimulation of cell proliferation.
      Injections of CCK-8S only transiently decreased the tissue levels of its
      receptor.

PMID- 11451155
TI  - An evolving paradigm of supervision within a changing health care environment.
AB  - As hospitals attempt to decrease their costs to survive in today's health care
      market, they are implementing resizing strategies that promise greater
      efficiency. A by-product has been the elimination of many management and
      supervisory positions. A self-administered questionnaire was sent to a stratified
      random sample of 750 hospitals (yielding a 46% return rate) to study the types of
      supervisory models being utilized and the factors associated with their
      differential use. While concern is expressed about the erosion of clinical
      supervision, the data suggests that the majority of social workers are receiving
      supervision from a social worker.

PMID- 11451156
TI  - Educational approaches for preparing social work students for interdisciplinary
      teamwork on geriatric health care teams.
AB  - Interest in teamwork has fluctuated over the last several decades, with recent
      renewed interest. As social workers become more involved in working with older
      people in the coming years, their success will hinge on collaboration with other
      health providers. Schools of social work and clinical sites must address this
      through the development of educational curricula and clinical programs which
      prepare social workers to work on interdisciplinary geriatric health care teams.
      Based on the experience of the national Geriatric Interdisciplinary Team Training
      (GITT) Program, this article presents an overview of the necessary team skills
      for social workers, educational methods for teach ing teamwork developed at the
      GITT sites, and some teaching challenges.

PMID- 11451157
TI  - A description of inappropriate hospital stays in selected in-patient services: a
      study of cases receiving social work services.
AB  - The number of discharges (63,303) from a university-affiliated medical center in
      Israel were reviewed. Eight percent of cases in three departments rcceivcd social
      work services. Patients experiencing inappropriate hospital stay (discharge
      delay) and who received social work services were characterized and compared with
      social work clients not experiencing delay. Discharge delay patients differed
      from other social work clients on key sociodemographic variables. Patients
      admitted because of "injury" were significantly more likely to experience delay
      than patients admitted because of "illness." "Waiting for community/institutional
      resources" was the most common reason for delay and discharge to an institutional
      setting increased the likelihood of delayed discharge. High risk factors were
      department-specific and should be studied in context. Results suggested the
      limited but positive impact of hospital-community collaborative strategies in
      reducing the incidence of delay over time.

PMID- 11451158
TI  - Social work practice with people with disabilities in the era of disability
      rights.
AB  - Social workers, especially those in health care and rehabilitation systems, must
      consider practice changes necessitated by recent legislation and the growing
      activism of disability rights groups. The authors review essential elements of
      the emerging sense of both oppression and empowerment that is occurring for many
      people with disabilities and groups; consider key aspects of ADA and other perti
      nent legislation that place new emphases on the self-determination of people with
      disabilities; and discuss what implications changing practice roles might have
      for social workers' relationships and patterns of interaction with other
      professionals in medical, health care and rehabilitation settings. The authors
      outline a beginning effort at designing a conceptual framework that promotes
      practice that: (1) maximizes clients' involvement in exploring an expanded range
      of options and choices; (2) prepares clients to be more effective in dealings
      with professionals, bureaucrats and agencies that often do not understand nor
      appreciate their need for self-determination; and (3) at the organizing level,
      mobilizes and helps to empower groups of people with disabilities to consider
      policy and program alternatives that can improve their situation. This framework
      may also be useful in work with people who have other long term care needs,
      chronic conditions.

PMID- 11451159
TI  - Experience and covariates of depressive symptoms among a cohort of HIV infected
      women.
AB  - OBJECTIVES: The objectives of this study are to assess (a) the level of
      depressive symptoms among a cohort of HIV infected women and comparable controls
      and (b) the relationship with covariates including socioeconomic status,
      substance use, social relations, disease status. METHODS: Participants were
      enrolled in the Women's Interagency HIV Study (WIHS). Depressive symptoms were
      measured using the Center for Epidemiological Studies Depression Scale (CESD).
      Data from 1993 HIV seropositive and 551 seronegative women are presented.
      RESULTS: Of HIV positive women 57.7% of HIV positive women scored 16 or higher on
      the CESD (ns) as compared to 55.0% of HIV negative women; at a cutoff of 23, the
      percents were 40.4% and 35.9% respectively (p = .06). The mean score was high
      19.8 but not significantly different between groups. Scores were higher among
      women who had less education, lower income, were of Hispanic ethnicity, used
      alcohol or drugs, experienced domestic abuse, had more than one partner, or had
      less supportive relationships. Among infected women, higher CESD scores were not
      significantly associated with CD4 cell count but were elevated for self-reported
      Class C AIDS defining clinical conditions. CONCLUSIONS: The scores on the CESD
      were elevated for both HIV positive and HIV negative women and the differences
      between the groups were small. Lower socioeconomic status and social support and
      higher substance use and domestic abuse were associated with depressive symptoms
      similarly for both groups.

PMID- 11451160
TI  - Hepatobiliary carcinoma in primary sclerosing cholangitis: a case control study.
AB  - BACKGROUND/AIMS: [corrected] Hepatobiliary carcinoma (HBC) has been considered to
      be a late complication of end-stage primary sclerosing cholangitis (PSC). The
      incidence of HBC is approximately 20% in PSC patients evaluated for liver
      transplantation. The diagnosis of HBC is difficult, at least at an early stage
      and the prognosis is poor even after liver transplantation. The aim of the study
      was to look for signs and risk factors for developing hepatobiliary carcinoma in
      patients with PSC. METHODS: Thirty-six consecutive patients with PSC and HBC (32
      with bile duct carcinoma, BDC, and four with hepatocellular carcinoma, HCC) were
      pair-matched to control patients referred for liver transplantation because of
      PSC but who did not have HBC. Gender and age at referral were used as matching
      factors. Clinical and biochemical data were registered. RESULTS: PSC patients
      with BDC had a shorter median duration of PSC (1 year) compared with the controls
      (7 years) and PSC patients with HCC (8 years). There were no statistically
      significant differences in the liver biochemistry between the patient groups.
      Varices were more common in patients with PSC and HCC (100%) than in controls
      (56%) or patients with PSC and HBC (12%) (P < 0.0005). CONCLUSIONS: The
      relatively short duration of PSC and the absence of varices in patients with BDC
      suggest that BDC, unlike HCC, is not necessarily a late complication of end-stage
      PSC, as was previously assumed.

PMID- 11451161
TI  - Autoantibodies of sera from patients with primary biliary cirrhosis recognize the
      alpha subunit of the decarboxylase component of human branched-chain 2-oxo acid
      dehydrogenase complex.
AB  - BACKGROUND/AIMS: The major antigens for anti-mitochondrial autoantibodies in
      primary biliary cirrhosis (PBC) are the lipoyl-containing components of 2-oxo
      acid dehydrogenase complexes. Autoantibodies against the E1alpha subunit of the
      pyruvate dehydrogenase complex (PDH) also have been found, but those against the
      E1alpha subunit of branched-chain 2-oxo acid dehydrogenase complex (BCKADH) have
      not been detected. We investigated the occurrence of BCKADH-E1alpha-specific
      autoantibodies by employing the purified human antigen. METHODS: The reactivities
      of PBC sera against purified antigens were assessed by ELISA and by
      immunoblotting analysis. The specificity of immunoreactivity was confirmed by
      absorption tests and affinity-purified antibodies. RESULTS: Fourteen out of 27
      PBC sera reacted with BCKADH-E1alpha, and these same sera also reacted with
      BCKADH-E2. No PBC sera reacted with BCKADH-E1beta. The reactivity of PBC sera
      with BCKADH-E1alpha was removed only when the sera were pre-absorbed with this
      antigen. However, reactivities to BCKADH-E2 and PDH-E1alpha were retained.
      Affinity-purified antibodies to BCKADH-E1alpha reacted with BCKADH-E1alpha, but
      not PDH-E1alpha. Thus, it was confirmed that anti-BCKADH-Elalpha did not cross
      react with either BCKADH-E2 or PDH-E1alpha. CONCLUSIONS: BCKADH-E1alpha-specific
      autoantibodies were found in the sera of PBC patients. The antibodies seem to
      occur subsequent to the anti-BCKADH-E2 antibody production, supporting the
      concept of intermolecular determinant spreading.

PMID- 11451162
TI  - Endothelin-1 plays a major role in portal hypertension of biliary cirrhotic rats
      through endothelin receptor subtype B together with subtype A in vivo.
AB  - BACKGROUND/AIMS: Endothelin-1 has been suggested to play a key role in cirrhotic
      portal hypertension, but a role of its receptors in vivo is not fully elucidated.
      METHODS: Biliary cirrhosis was induced by bile duct ligation. Expressions of
      endothelin-1 and its receptors were evaluated by radioimmunoassay and/or reverse
      transcription polymerase chain reaction. Hemodynamics were studied using
      endothelin receptor agonist or antagonist. RESULTS: Portal pressure and hepatic
      endothelin-1 concentrations progressively increased in parallel after bile duct
      ligation. Gene expression of hepatic prepro-endothelin-1 and endothelin B
      receptor enhanced after bile duct ligation, while that of endothelin A receptor
      was unchanged. Intraportal administration of endothelin-1 or endothelin B
      receptor agonist sarafotoxin 6c (0.5 nmol/kg, respectively) progressively raised
      portal pressure in both sham and cirrhotic rats. Portal hypertensive effect of
      sarafotoxin 6c was more intense in cirrhotic rats than sham animals. Neither
      endothelin A receptor antagonist FR139317 (1 mg/kg) nor endothelin B receptor
      antagonist BQ788 (1 mg/kg) alone ameliorated cirrhotic portal hypertension. Only
      the combined endothelin A and B blockade was associated with a decrease in portal
      pressure in cirrhotic rats. CONCLUSIONS: These results indicate that endothelin-1
      plays a major role in cirrhotic portal hypertension through endothelin receptor
      subtype B together with subtype A in vivo.

PMID- 11451163
TI  - Increased heme oxygenase activity in splanchnic organs from portal hypertensive
      rats: role in modulating mesenteric vascular reactivity.
AB  - BACKGROUND/AIMS: We have recently demonstrated that heme oxygenase-1 is
      upregulated in splanchnic organs of portal hypertensive rats. In the present
      study, we assessed whether heme oxygenase enzymatic activity is increased in
      splanchnic organs of portal hypertensive rats, and the relative contribution of
      heme oxygenase and nitric oxide synthase to the vascular hyporeactivity in portal
      hypertension. METHODS: Heme oxygenase activity was measured in splanchnic organs
      of portal hypertensive and sham-operated rats. The effects of heme oxygenase and
      nitric oxide synthase inhibition on pressure responses to potassium chloride and
      methoxamine were assessed in perfused mesenteric vascular beds of portal
      hypertensive and sham-operated rats. RESULTS: Heme oxygenase activity was
      increased in the mesentery, intestine, liver, and spleen of portal hypertensive
      rats. The hyporeactivity to potassium chloride in portal hypertensive rats was
      overcome after simultaneous inhibition of both heme oxygenase and nitric oxide
      synthase, but only partially attenuated after nitric oxide synthase inhibition
      alone. The hyporeactivity to methoxamine was completely reversed after nitric
      oxide synthase blockade. CONCLUSIONS: These results demonstrate that heme
      oxygenase activity is increased in splanchnic organs of portal hypertensive rats.
      They also suggest that heme oxygenase contributes to the hyporeactivity to
      potassium chloride, but not to methoxamine, in portal hypertensive rats.

PMID- 11451164
TI  - Increase of serum estradiol in cirrhotic men treated by transjugular intrahepatic
      portosystemic stent shunt.
AB  - BACKGROUND/AIMS: Liver cirrhosis is frequently associated with sexual dysfunction
      and hormonal abnormalities. To evaluate the effect of portosystemic shunting on
      sex steroid serum concentrations, a prospective study was performed in cirrhotic
      patients treated consecutively and electively by transjugular intrahepatic
      portosystemic stent shunt (TIPS). METHODS: In 27 patients with liver cirrhosis we
      measured serum levels of testosterone (T), sexual hormone binding globulin
      (SHBG), luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone
      sulfate, androstenedione (A), estradiol (E2), 17-OH-progesterone and the T/SHBG
      ratio before and 3 months after TIPS. RESULTS: In men (n = 17) 3 months after
      TIPS, A and E2 significantly increased, with mean serum levels rising from 4.4 +/
      2.5 to 5.6 +/- 2.9 ng/ml (P = 0.04) and from 27 +/- 9 to 40 +/- 19 pg/ml (P =
      0.003), respectively. In contrast to A the increase of E2 persisted at 9 and 15
      months after TIPS. Erectile dysfunction increased from 30% before TIPS to 70%
      after TIPS. In women (n = 10) A and E2 levels did not change significantly after
      TIPS. CONCLUSIONS: TIPS aggravated hormonal dysbalance of sex steroids in favor
      of estrogens (hyperestrogenism) in men.

PMID- 11451165
TI  - Increased intracranial pressure in a porcine model of fulminant hepatic failure
      using amatoxin and endotoxin.
AB  - BACKGROUND/AIMS: The purpose of this study was to develop a clinically relevant
      porcine model of fulminant hepatic failure (FHF) by means of administration of
      amatoxin and endotoxin. METHODS: Pigs were intraportally administered only saline
      in group 1 (n = 3), 1 microg/kg of lipopolysaccharide (LPS) in group 2 (n = 4),
      0.1 mg/kg of alpha-amanitin in group 3 (n = 5), and amanitin plus LPS in group 4
      (n = 9). RESULTS: All the pigs in groups 1 and 2 survived with minimal changes in
      liver function tests. In contrast to the 60% mortality in group 3, all the pigs
      in group 4 died within 96 h, with a significant increase in aspartate
      transaminase at 24 h (9,757 +/- 2,167 IU/I). In addition, they demonstrated
      severe metabolic disorders, such as serum lactate accumulation, hypoglycemia,
      coagulopathy, plasma amino acid imbalance, and hyperammonemia. The intracranial
      pressure significantly increased to 17.8 +/- 2.5 mmHg immediately before death.
      Reversal of FHF in these pigs following orthotopic liver transplantation
      confirmed that the toxicity is liver-specific and that the graft liver is
      unaffected. CONCLUSIONS: This porcine model of FHF induced by a combination of
      amanitin and LPS will be of much use in the development of new therapies for
      human FHF.

PMID- 11451166
TI  - Continuous intravenous infusion of deleted form of hepatocyte growth factor
      attenuates hepatic ischemia-reperfusion injury in rats.
AB  - BACKGROUND/AIMS: Although beneficial roles of hepatocyte growth factor (HGF) and
      its variants on several hepatic disorders have been reported, their effects on
      hepatic ischemia-reperfusion (IR) injury remain undetermined. We investigated the
      action of a deleted form of HGF (dHGF) on hepatic IR injury in rats. METHODS:
      dHGF or phosphate-buffered saline was continuously infused intravenously for 20 h
      prior to a 20-min occlusion of hepatic vessels. Samples were taken before and
      after IR, for measurement of serum dHGF and released enzymes, liver gamma
      glutamylcysteinyl glycine (GSH) level, as well as histological and
      immunohistochemical examinations. RESULTS: After reperfusion, histological
      injury, as well as increase in the serum activities of aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine
      kinase-BB were significantly attenuated in the dHGF-treated rats. dHGF maintained
      a high GSH level and suppressed oxidative stress and intercellular adhesion
      molecule-1 (ICAM-1) expression on sinusoidal endothelial cells (SECs), on which c
      Met was not detected. IR caused activation of c-Met expression, which was milder
      in the dHGF-treated group, in hepatocytes at the pericentral region. CONCLUSIONS:
      dHGF attenuated liver injury after IR. It also maintained a higher GSH level,
      depressed oxidative stress and inhibited ICAM-1 expression on c-Met negative
      SECs, suggesting a paracrine effect of dHGF.

PMID- 11451167
TI  - Genome-wide analyses on loss of heterozygosity in hepatocellular carcinoma in
      Southern China.
AB  - BACKGROUND/AIMS: To conduct a genome-wide analysis of loss of heterozygosity
      (LOH) and its clinical significance in hepatocellular carcinoma (HCC) in Southern
      China where high incidence of HCC was documented. METHODS: LOH of 382
      microsatellite loci on all autosomes were detected with polymerase chain reaction
      based microsatellite polymorphism analyses in 104 HCC tumor tissues. RESULTS:
      High frequency of LOH (>55.7%) was observed on chromosome 1p, 1q, 2q, 3p, 4q, 6q,
      8p, 9p, 13q, 16q, and 17p. LOH rates on loci D4S2964 (4q21.21), D8S277 (8p23.1
      pter) and D17S938 (17p13.1-p13.3) were significantly higher in cases with
      positive HBsAg than in those with negative HBsAg. Similarly, LOH on loci D1S214
      (lp36.3), D1S2797 (1p34) and D3S3681 (3p11.2-p14.2) were more frequently detected
      in tumors with intrahepatic metastasis than in those without. CONCLUSIONS: Status
      of LOH in HCC in Southern China is similar to that reported previously in other
      countries and areas. However, we firstly identified high-frequency LOH on
      chromosome 3p in HCC. Furthermore, HBV infection, as well as tumor intrahepatic
      metastasis, may be correlated with allelic losses on certain chromosome regions.

PMID- 11451168
TI  - Endothelial cell marker expression in dysplastic lesions of the liver: an
      immunohistochemical study.
AB  - BACKGROUNDS/AIMS: Hepatocellular carcinoma usually contains continuous capillary
      vessels lacking the differentiation markers specific for normal sinusoidal
      endothelial cells. We therefore aimed to search for alterations in endothelial
      cell marker expression in precancerous liver lesions. METHODS: Expression of the
      endothelial cell markers CD31, CD34 and BNH9 was analyzed in 138 dysplastic
      lesions from 40 cirrhotic patients (20 with and 20 without hepatocellular
      carcinoma). RESULTS: No expression of the three endothelial cell markers was
      detected in cirrhotic nodules and in non dysplastic regenerative macronodules.
      The three markers were detected in 29.8% of dysplastic lesions and 47% of
      hepatocellular carcinomas. At least one marker was detected in 75% of dysplastic
      lesions and 100% of hepatocellular carcinomas. The three markers were more
      frequently expressed in areas of small cell than of large cell change (34 vs
      10%). No correlation was found with the grade of dysplasia, the occurrence of
      arterialization and the association with hepatocellular carcinoma. CONCLUSIONS:
      Alterations in the hepatic microcirculation comparable to those observed in
      hepatocellular carcinoma are present in a significant proportion of dysplastic
      lesions of the liver and may be indirect markers of the process of liver
      carcinogenesis.

PMID- 11451169
TI  - Estrogen upregulates nitric oxide synthase expression in cultured rat hepatic
      sinusoidal endothelial cells.
AB  - BACKGROUND/AIMS: Estrogen receptor (ER) is present in vascular endothelial cells
      and estrogen promotes nitric oxide (NO) synthesis, which relaxes smooth muscle
      cells. It is also speculated that NO is synthesized by estrogen in hepatic
      sinusoidal endothelial cells (SECs). Here we investigated the localization of ER
      and endothelial cell nitric oxide synthase (ecNOS), and determined 17beta
      estradiol (E2)-induced ecNOS expression in normal rat SECs. METHODS: Cultured
      SECs were used. Fluorescence intensities of ecNOS were measured by
      immunofluorescence using a confocal laser-scanning microscope. E2 was added (100
      pg/ml) to the culture medium, and the expressions of ecNOS mRNA and protein were
      analyzed by reverse-transcription polymerase chain reaction and Western blotting.
      NO production in cultured SECs was examined using diaminofluorescein-2 diacetate
      as a fluorescent indicator for NO. RESULTS: Immunolocalization of ER and ecNOS in
      normal liver was demonstrated in endothelial cells lining the hepatic sinusoids.
      ER and ecNOS were localized in the nuclei and cytoplasm of cultured SECs,
      respectively. The mRNA expression of ecNOS in cultured SECs was increased after 6
      h, and the protein expression of ecNOS was increased 24 h after E2 stimulation.
      The fluorescence intensity of NO in cultured SECs was increased by E2 stimulation
      compared with untreated control cells. CONCLUSIONS: These results suggested that
      ER is present in SECs, and estrogen upregulates NO production in SECs. E2 may be
      involved in the regulation of the hepatic sinusoidal microcirculation.

PMID- 11451170
TI  - Identification of cyclosporine A and tacrolimus glucuronidation in human liver
      and the gastrointestinal tract by a differentially expressed UDP
      glucuronosyltransferase: UGT2B7.
AB  - BACKGROUND/AIMS: The oral administration of the major transplant
      immunosuppressants cyclosporine A and tacrolimus leads to unpredictable drug
      levels requiring drug monitoring. Hepatic and extrahepatic metabolism of
      cyclosporine A and tacrolimus by cytochrome P450 proteins has been analyzed but
      metabolism and inactivation by glucuronidation has not been investigated.
      METHODS: Cyclosporine A and tacrolimus glucuronidation was measured in hepatic
      and gastrointestinal microsomal protein, and with 11 recombinant hepatic and
      extrahepatic family 1 and 2 UDP-glucuronosyltransferases. UDP
      glucuronosyltransferase transcripts were determined by polymerase chain reaction.
      RESULTS: Significant cyclosporine and tacrolimus glucuronidation activity was
      present in endoplasmic reticulum from liver, duodenum, jejunum, ileum and colon,
      but was absent in stomach. Specific cyclosporine A glucuronidation activity was
      highest in liver and colon, tacrolimus glucuronidation was highest in liver.
      Analyses using recombinant UDPglucuronosyltransferases identified UGT2B7 as a
      human UDP-glucuronosyltransferase with specific activity toward cyclosporine A
      and tacrolimus. The hepato-gastrointestinal distribution of immunosuppressant
      glucuronidation activity corresponded to the differential expression pattern of
      UGT2B7 mRNA. CONCLUSIONS: This study provides conclusive evidence of hepatic and
      extrahepatic immunosuppressant glucuronidation by human UGT2B7 which was
      identified to be differentially expressed in the human hepatogastrointestinal
      tract. Hepatic and extrahepatic glucuronidation may influence the therapeutic
      efficacy of transplant immunosuppressants.

PMID- 11451171
TI  - Developmental regulation of the concentrative nucleoside transporters CNT1 and
      CNT2 in rat liver.
AB  - BACKGROUND/AIMS: The pattern of nucleoside transporter expression in hepatocytes
      was studied in the developing rat liver. METHODS: Hepatocytes isolated from
      fetuses, neonates and adult rats were used for uridine uptake measurements and
      concentrative nucleoside transporter (CNT) expression. RESULTS: Adult hepatocytes
      showed the highest Na-dependent uridine uptake, but fetal hepatocytes exhibited a
      significant NBTI-sensitive component of equilibrative Na+-independent transport,
      which was either negligible or absent in neonatal and adult rat hepatocytes. Low
      Na+-dependent uridine uptake was associated with low amounts of CNT1 and CNT2
      transporter proteins, both with apparent Km values in the low micromolar range.
      Hepatocyte primary cultures from 20-day-old fetuses showed very low amounts of
      CNT2 mRNA, and expressed both carrier proteins. Incubation of fetal hepatocytes
      with dexamethasone and T3 resulted in a significant increase in Na+-dependent
      uridine uptake and an accumulation of the CNT2 protein and mRNA. CONCLUSIONS: The
      expression of concentrative nucleoside carriers in hepatocytes from developing
      rat liver is developmentally regulated. Addition of endocrine factors known to
      induce differentiation of fetal hepatocytes results in selective up-regulation of
      CNT2 expression.

PMID- 11451172
TI  - Effect of phenobarbital on the expression of bile salt and organic anion
      transporters of rat liver.
AB  - BACKGROUND/AIMS: The hepatic clearance of drugs and cholephilic organic anions is
      stimulated by phenobarbital (PB). Our aim was to analyze the effects of PB on the
      expression of hepatocellular bile salt and organic anion transporters. METHODS:
      Male Sprague-Dawley rats were treated intraperitoneally with PB (80 mg/kg/d) or
      saline for 5 days. Transporter expression was quantified by northern and western
      blot analysis and initial uptake rates of bromosulphophthalein (BSP) and digoxin
      were measured in isolated hepatocytes. RESULTS: Compared to control rats, PB
      treatment increased expression of the organic anion transporting polypeptide 2
      (Oatp2; Slc21aS) more than 2-fold on the RNA (P < 0.05) and protein (P < 0.001)
      levels. Expression of Oatpl (Slc21al), Oatp4 (Slc21a6) and the Na+-taurocholate
      cotransporting polypeptide (Ntcp; Slc10a1) was unaltered. At the canalicular
      pole, expression of the bile salt export pump (Bsep; ABCB11) and of the multidrug
      resistance proteins 2 (Mrp2; ABCC2) and 6 (Mrp6; ABCC6) was not significantly
      changed. Whereas hepatocellular BSP uptake was unaffected by PB, digoxin uptake
      was stimulated 4-fold. CONCLUSIONS: The induction of digoxin uptake by PB
      correlates with Oatp2 expression. In contrast, the lack of increase of Oatpl and
      Oatp4 expression is in accordance with unchanged BSP uptake. These data challenge
      the previously held view that PB induces hepatocellular BSP uptake systems.

PMID- 11451173
TI  - Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term
      prophylaxis of hepatitis B recurrence after liver transplantation.
AB  - BACKGROUND/AIMS: The long-term prophylaxis of hepatitis B after liver
      transplantation requires further optimization. In a randomized trial we
      investigated a regimen where the initially given hepatitis B immunoglobulin
      (HBIg) is replaced by long-term lamivudine treatment. METHODS: Twenty-four liver
      transplant recipients (all HBsAg-positive/HBV DNA-negative before
      transplantation), who had received HBIg for at least 6 months without HBV
      recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for
      52 weeks. The efficacy criteria involved seronegativity for HBsAg and
      undetectable HBsAg/ HBcAg in the liver. RESULTS: Twenty-one of 24 patients
      completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten
      on lamivudine), while three patients became HBsAg-positive. Amongst those without
      HBV recurrence HBV DNA was detectable only by polymerase chain reaction,
      intermittently in serum and lymphocytes, and in liver specimens from six of eight
      patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was
      found in four cases with no viral antigen expression. Eight patients continued
      lamivudine after the study and during an additional 6-22 months remained HBsAg
      negative with normal graft function. CONCLUSIONS: Substitution of HBIg with
      lamivudine is effective for prevention of HBV recurrence in low-risk liver
      transplant recipients and offers a convenient and cost-effective alternative for
      long-term HBV prophylaxis.

PMID- 11451174
TI  - Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis
      B reinfection after liver transplantation possible role of mutations in the YMDD
      motif prior to transplantation as a risk factor for reinfection.
AB  - BACKGROUND/AIMS: Reinfection with hepatitis B virus (HBV) after liver
      transplantation (OLT) is associated with an unfavourable clinical course.
      Lamivudine/hepatitis B immune globulin (HBIG) combination treatment reduces
      reinfection rates. However, it is unclear at what time point lamivudine should be
      started and which HBIG doses are sufficient. METHODS: Twenty-one patients
      receiving combination treatment were studied. Lamivudine was started up to 16.5
      months before OLT and continued thereafter. HBIG was started intraoperatively and
      continued according to anti-HBs-titers. Median follow-up after OLT was 20 months.
      RESULTS: Eleven patients received lamivudine pretreatment for >2 (median 6)
      months due to initial HBV-DNA-positivity (median 749 pg/ml). After initial
      lamivudine response HBV-DNA increased in two of them to concentrations above 10
      pg/ml prior to OLT. Both had developed mutations in the YMDD motif and suffered
      from HBV reinfection 13 and 75 days postoperatively. Individual HBIG consumption
      was highly variable (range 787-4,766 lU/month). Twenty-two percent of anti-HBs
      titers measured before HBIG administration were below 100 IU/l. CONCLUSIONS:
      Combined reinfection prophylaxis with lamivudine and HBIG is effective in
      patients with controlled viral replication at the time of OLT. However,
      pretransplantation lamivudine resistance is a risk factor for reinfection. Low
      dose HBIG maintenance therapy individualized according to anti-HBs-titers appears
      to be tenable.

PMID- 11451175
TI  - Prevention of hepatitis B virus recurrence after liver transplantation in
      cirrhotic patients treated with lamivudine and passive immunoprophylaxis.
AB  - BACKGROUND/AIMS: Treatment with hepatitis B virus immune globulins (HBIG) or
      lamivudine has reduced the rate of hepatitis B recurrence after liver
      transplantation to approximately 50%. METHODS: To further decrease hepatitis B
      recurrence, 33 hepatitis B virus (HBV)-related cirrhotic patients were treated
      with lamivudine before liver transplantation and with lamivudine together with
      low-dose HBIG (46 500 IU the first month followed by 5,000 lU/monthly) after
      surgery. RESULTS: While on lamivudine, serum HBV DNA level decreased
      significantly in all patients and in 11 (33%) the Child-Pugh score improved.
      Twenty-six patients were transplanted. Among the 25 who survived for longer than
      12 months, only one (4%) experienced a hepatitis B recurrence over an average
      follow-up of 31 months, a rate significantly lower (P = 0.0002) than the 50%
      recurrence rate among a historical control group of 12 patients. However, low
      level HBV replication was detected sporadically throughout the follow-up in 64%
      of patients. CONCLUSIONS: Over the medium-term, combined prophylaxis with
      lamivudine and HBIG significantly decreases the risk of hepatitis B recurrence
      after liver transplantation. Though low-level HBV infection recurred in two
      thirds of patients, the pathogenic expression of HBV was prevented.

PMID- 11451176
TI  - Factors influencing ribavirin-induced hemolysis.
AB  - BACKGROUND/AIMS: One of the major side effects of the combination therapy for
      chronic hepatitis C is ribavirin-induced hemolytic anemia. Little is known about
      variables influencing this anemia. Our study tried to search for these variables
      in a large group of patients with hepatitis C treated with the combination
      therapy. METHODS: Two hundred and forty-four patients chronically infected with
      the hepatitis C virus were treated either with induction treatment (daily dose of
      interferon) or with a standard treatment (interferon thrice weekly). Both groups
      received 1,000-1,200 mg of ribavirin from week 4 until the end of the treatment.
      The drop in hemoglobin level was defined as the difference between the
      pretreatment hemoglobin level and the hemoglobin level at week 8. Seventeen
      variables which could possibly influence this drop in hemoglobin level were
      examined. RESULTS: After multivariate analysis, the drop in hemoglobin level was
      only significant influenced by pretreatment platelet level, treatment and
      haptoglobin phenotype. The ribavirin dose did not influence the drop in
      hemoglobin level or the early virological response. CONCLUSIONS: Ribavirin
      induced hemolysis is influenced by the pretreatment platelet level, the
      administered amount of alpha-interferon and the haptoglobin phenotype. A careful
      search for the minimal dose of ribavirin needed in combination treatment is
      necessary.

PMID- 11451177
TI  - Efficacy and limitations of a specific immunotherapy in chronic hepatitis B.
AB  - BACKGROUND/AIMS: This controlled study aimed to evaluate the efficacy and
      potential side effects of hepatitis B virus (HBV) vaccination as active
      immunotherapy in HBV-related chronic hepatitis. METHODS: The 118 included
      patients were 'naive' subjects who had never received any previous anti-HBV
      therapy, showed detectable serum HBV DNA and had biopsy-proven chronic hepatitis.
      In a 12-month follow-up they were given either five intramuscular injections of
      20 microg of a preS2/S (GenHevac B, Pasteur-Merieux) (n = 46) or an S vaccine
      (Recombivax Merck & Co.) (n = 34) or no treatment as a control (n = 37). The
      efficacy of vaccination was evaluated by testing for serum HBV DNA negativation
      using a standard liquid hybridization assay. RESULTS: Three months after the
      first three vaccine injections, the percentage of serum HBV DNA negativation was
      higher in the vaccine groups (16.3%) than in the control group (2.7%) (P = 0.033,
      by the chi2 Pearson test) and was more frequently observed in patients who had
      pretreatment viremia >200 pg/ml (none in the control group vs. 16.7% in the
      vaccinated groups) (P = 0.025). After 12 months follow-up and five vaccine
      injections, there was no difference in the rate of serum HBV DNA negativation
      between vaccinated and unvaccinated subjects but HBV vaccines significantly
      decreased the HBV viral load between the sixth and twelfth months (P = 0.04) in
      contrast with the control group. The rate of HBe/anti-HBe seroconversion after 6
      months of follow-up occurred only in eight (13.3%) vaccinated patients and in one
      (3.6%) of the controls. Disappearance of serum HBsAg was not observed in any of
      the patients. CONCLUSIONS: This controlled study offers direct evidence that the
      HBV vaccine may decrease HBV replication in chronic hepatitis B patients. It also
      emphasizes the need for reinforced immunization strategies as well as combination
      therapies.

PMID- 11451178
TI  - Identification of hepatitis B virus-specific CTL epitopes presented by HLA
      A*2402, the most common HLA class I allele in East Asia.
AB  - BACKGROUND/AIMS: The aim of this study was to identify and characterize hepatitis
      B virus (HBV)-specific cytotoxic T lymphocytes (CTL) epitopes presented by human
      leukocyte antigen (HLA)-A*2402, most common HLA class I allele in East Asia.
      METHODS: HLA-A*2402-restricted CTL epitopes were identified by reverse
      immunogenetics. Immunogenecity of these epitopes was investigated using
      peripheral blood mononuclear cell (PBMC) from HLA-A24+ patients with acute
      hepatitis B. RESULTS: An HLA-A*2402 stabilization assay demonstrated that 36 of
      63 HBV peptides carrying HLA-A*2402 anchor residues have high- and medium-HLA
      A*2402 binding affinity. Two (C117-125 and P756-764) of the 36 peptides induced
      peptide-specific CTLs. CTL clones and lines specific for these peptides killed
      HBV recombinant vaccinia virus-infected target cells expressing HLA-A*2402,
      indicating that these two peptides are CTL epitopes presented by HLA-A*2402.
      These two peptides were able to induce specific CTLs in 7 and 11 of 12 HLA-A24+
      patients with acute hepatitis B, respectively. CONCLUSIONS: We identified two
      immunodominant CTL epitopes restricted by HLA-A*2402. Because HLA-A*2402 is the
      most common allele in East Asia, a region in which there are approximately 200
      million HBV carriers, these epitopes will be useful for analysis of CTL responses
      in patients from East Asia.

PMID- 11451179
TI  - A novel cytotoxic T-cell epitope presented by HLA-A24 molecule in hepatitis C
      virus infection.
AB  - BACKGROUND/AIMS: It has been suggested that cytotoxic T lymphocytes (CTL) have
      crucial roles for the hepatocellular damage in hepatitis C virus (HCV) infection.
      A series of CTL epitopes located in the HCV protein have been identified.
      However, no CTL epitopes restricted by HLA-A24, a common HLA allele in humans,
      has been identified. METHODS: Peripheral blood and liver infiltrating mononuclear
      cells from the patients with hepatitis C virus infection and healthy controls
      were stimulated with a series of peptides containing HLA-A24 binding motifs
      located in HCV protein. RESULTS: An immunodominant HLA-A24 restricted CTL epitope
      (A24-4; AYSQQTRGL, amino acids 1031-1039) presented by HLA-A24 molecule was
      identified using a series of synthetic peptides containing the HLA-A24 binding
      motifs. The CTL activity against this peptide was induced both in peripheral
      blood and liver infiltrating mononuclear cells from HLA-A24-positive chronic
      hepatitis C patients, not from HLA-A24-negative patients and HLA-A24-positive
      healthy controls. CTL activity was blocked by anti-HLA-A24 and anti-CD8
      antibodies, not by anti-CD4 antibody. Furthermore, the A24-4-specific CTL
      recognized the HCV gene transfected target cells. CONCLUSIONS: Because this
      peptide is presented by a common HLA class I molecule, it might be useful for
      protection against hepatocellular damage and vaccine development in large
      population of the HCV-infected patients.

PMID- 11451180
TI  - Heme oxygenase: protective enzyme or portal hypertensive molecule?

PMID- 11451181
TI  - The inflammatory basis of intracranial hypertension in acute liver failure.

PMID- 11451182
TI  - Liver transplantation and hepatitis B virus infection: the situation seems to be
      under control, but the virus is still there.

PMID- 11451183
TI  - Novel roles for glutathione in gene expression, cell death, and membrane
      transport of organic solutes.

PMID- 11451184
TI  - Immature hepatic tumor of bimodal differentiation in a young adult patient: a
      novel lesion expressing beta-catenin and mimicking a distinct phase of
      hepatogenesis.
AB  - PATIENT AND METHODS: A large right-sided liver tumor was incidentally discovered
      and totally resected in a 21-year-old female patient without chronic liver
      disease. Histopathologic examination revealed that this malignant tumor does not
      fit any of the known types of primary liver tumors reported thus far. RESULTS:
      The lesion chiefly consisted of numerous solid nests composed of immature
      epithelial cells disclosing a marker profile typical for hepatocytes and strongly
      expressing beta-catenin. These nests were tightly associated with abnormal duct
      like profiles exhibiting features of bile duct cells. CONCLUSIONS: The finding of
      numerous neoplastic hepatobiliary units ('liverlets') suggests that this tumor
      may mimic a distinct developmental phase of hepatogenesis close to ductal plate
      formation.

PMID- 11451185
TI  - Intense isolated expression with preS1 (large protein) antibodies in the liver
      graft associated with severe acute hepatitis B virus reactivation.

PMID- 11451186
TI  - Low prevalence of hepatitis C virus antibody among Swiss dental health care
      workers.

PMID- 11451187
TI  - Ulcerative colitis associated with interferon treatment for chronic hepatitis C.

PMID- 11451188
TI  - Development of lupic anticoagulant during combination therapy in a patient with
      chronic hepatitis C.

PMID- 11451189
TI  - Contractures in orthopaedic and neurological conditions: a review of causes and
      treatment.
AB  - PURPOSE: To examine the techniques used for the treatment of contracture in the
      context of current scientific knowledge of muscle. METHOD: Synthesis of data
      available from MEDLINE, RECAL, EMBASE, the Cochrane Library and relevant texts.
      RESULTS: The development of contractures through immobilisation, muscle weakness
      and spasticity is described. The effects of passive stretching, continuous
      passive movement, serial plastering, splinting, electrical stimulation, botulinum
      injections and surgical tenotomies in the treatment of contractures in persons
      with neurological and orthopaedic conditions are identified. The strengths and
      weaknesses of these modalities are discussed. CONCLUSION: Predisposing factors
      persist after treatment of contractures thus for treatment to be effective long
      term management programmes need to be developed. New treatment techniques, used
      in series or combined, offer the prospect of improved management of contracture.
      Scientific and clinical research is needed to investigate the effect of
      contracture treatment.

PMID- 11451190
TI  - Association between personal and environmental factors and the occurrence of
      handicap situations following a stroke.
AB  - BACKGROUND AND PURPOSE: Little is known about the potential role of environmental
      factors in the handicap creation process following a stroke. The objective of
      this study was to explore the presence of a relationship between environmental
      factors and the occurrence of handicap following a stroke, taking into
      consideration age and the level of impairments and disabilities. METHODS: This is
      a cross-sectional study where data were collected 6 months after discharge from
      an intensive functional rehabilitation unit. A convenience sample of 51
      participants was recruited at the time of their admission to the rehabilitation
      unit for rehabilitation post-stroke. Perceived influence of environmental factors
      was measured using the Measure of the Quality of the Environment (MQE). Handicap
      situations were measured with the Assessment of Life Habits (LIFE-H). Impairments
      and disabilities comprised six domains (cognition, perception. depression,
      communication, sensorimotor function and comorbidity) assessed using a variety of
      measuring tools from which a composite score was derived. RESULTS: Fifty-one
      participants aged 40-97 years old took part in this study. Perceived obstacles in
      the environment, together with age and the level of impairments and disabilities,
      explained 58.9% of the variation in the LIFE-H (handicap level). Taken alone, the
      perceived obstacles (total score) explained 6.2%. The perceived facilitators
      (total score) in the environment were not found to be related to the presence of
      handicap situations. CONCLUSION: Increased level of impairments and disabilities.
      advanced age and perceived barriers in the physical and social environment
      contribute to the handicap creation process following a stroke.

PMID- 11451191
TI  - Hand-arm vibration exposure influences performance of daily activities.
AB  - PURPOSE: Although much research has been performed on the effects of vibration on
      nerves, muscles and vascular structures, little is known of the effects that
      vibration exposure to handheld tools can give on the ability to perform
      activities of daily living. The objective of the present study was to analyse the
      consequences of vibration exposure on performance of daily activities. METHOD: In
      a total group of 105 exposed male workers, a standardized self-administered ADL
      questionnaire, the EDAQ including 102 activity items plus 22 diagnosis-specific
      activity items, was filled out. RESULTS: Forty-four workers (42%) expressed one
      or more difficulties in performing daily activities in the total study group. The
      data demonstrated that pain and reduced grip force showed a strong correlation
      with difficulties in performing daily activities. CONCLUSION: Working in a cold
      environment, using vibrating machines. handwriting, picking up small objects,
      opening lids, lifting and carrying were activities perceived as most difficult to
      accomplish.

PMID- 11451192
TI  - Opinion statement on the minimal acceptable standards of healthcare in cerebral
      palsy.
AB  - PURPOSE: Recent studies have shown a marked variation in the standards of
      healthcare for young people with disabilities in different regions of the UK and
      even within the same health district. Equity in the provision of healthcare is a
      fundamental principle of the NHS. However, this can only be measured against an
      agreed minimal standard of healthcare that serves as a benchmark for healthcare
      purchasers and providers. The aim of the present document is to develop a set of
      minimum standards of healthcare for children and adults with cerebral palsy (CP).
      METHODS: The document was developed in two stages by a multi-professional and
      multi-disciplinary group of practitioners in the field of CP. Initially, members
      of the panel jointly formulated a statement of what they believed should be the
      minimal acceptable standards of healthcare in CP drawing on their own experience
      and the published scientific evidence. In the second stage the views of some of
      the relevant professional bodies and voluntary organizations on the draft
      statement were sought. The responses of these organizations were incorporated
      into the final document if agreed by the panel. RESULTS AND CONCLUSIONS: Twenty
      two recommendations were made. These were considered the minimum standards of
      care in a district general hospital. The emphasis was on the organisation and
      delivery of healthcare for children with CP. The statement is intended to
      stimulate debate especially in relation to the equity of service provision
      throughout the country and may be used to inform purchasers of healthcare.
      Similarly, it may also be useful to providers of healthcare as an audit tool.

PMID- 11451193
TI  - To be and to become: the changing focus of developmental paediatrics.

PMID- 11451194
TI  - Commentary on the article by Bakheit et al. 'Opinion statement on the minimal
      standards for healthcare in cerebral palsy'.

PMID- 11451196
TI  - Opinion statement on the minimal standards of healthcare in cerebral palsy.

PMID- 11451195
TI  - Reasonable expectations for minimum standards.

PMID- 11451197
TI  - Towards improving care in cerebral palsy.

PMID- 11451198
TI  - Suppression of matrix metalloproteinase-2 and -9 mediated invasiveness by a novel
      matrix metalloproteinase inhibitor, BE16627B.
AB  - Cell invasion is a nature of malignant gliomas, demeriting to many efforts of the
      treatment. Matrix metalloproteinase (MMP) is acknowledged as a key factor in this
      complicated process. The aim of this study was to investigate whether inhibition
      of MMP activity in malignant glioma cells could be achieved by a novel agent,
      BE16627B (BE). Malignant glioma cell lines, U87MG, U251MG, and U373MG, were
      employed to evaluate inhibitory effect on zymogram, type IV collagenolysis assay,
      and haptoinvasion assay for 24 h exposure of BE, following preliminar

PMID- 11451199
TI  - Role of ceramide during cisplatin-induced apoptosis in C6 glioma cells.
AB  - Cisplatin is commonly used for the treatment of malignant brain tumors. However,
      the mechanisms of cell death by cisplatin are not fully understood. Therefore,
      the present study was designed to elucidate the apoptotic signaling pathway(s)
      activated by cisplatin in a C6 rat glioma cell line. C6 cells were treated with
      various concentrations of cisplatin (0.2-10 microg/ml) for 24-72 h. At 10
      microg/ml cisplatin, over 90% of the cells became dead at 72 h. Apoptotic death
      was confirmed by condensation and fragmentation of nuclei, and DNA laddering.
      Even in cells treated with 1.5 microg/ml cisplatin, typical apoptotic cells were
      observed at 72 h. The intracellular level of ceramide, measured Escherichia coli
      diacylglycerol kinase markedly increased during 24-72 h after the addition of 10
      microg/ml cisplatin. The activity of caspase-3(-like) proteases increased and
      reached a peak at 48 h. Inhibitors of caspases reduced the number of apoptotic
      cells. Pretreatment of C6 cells with glutathione or N-acetyl-cysteine, which are
      known to block the activation of neutral magnesium-dependent sphingomyelinase,
      inhibited ceramide formation, leading to suppression of both activation of
      caspase-3(-like) proteases and apoptosis by cisplatin. In contrast, pretreatment
      of the cells with N-oleoylethanolamine (OE), a ceramidase inhibitor, potentiated
      apoptosis induced by cisplatin. Furthermore, OE enhanced sensitivity of the
      cisplatin-resistant cells to cisplatin. These results suggest that ceramide is
      closely implicated in apoptosis of glioma cells by cisplatin through activation
      of caspase-3(-like) proteases.

PMID- 11451200
TI  - Sensitization of human malignant glioma cell lines to tumor necrosis factor
      induced apoptosis by cisplatin.
AB  - Most tumors, including gliomas, are resistant to tumor necrosis factor (TNF)
      cytotoxicity unless protein or RNA synthesis is inhibited. We investigated the
      effects of the combined use of TNF-alpha and cisplatin (CDDP) on cultured
      malignant glioma cells, T98G, U373MG, A172, and U87MG. All glioma cell lines were
      sensitive to treatment with CDDP but resistant to TNF-alpha during 24 h
      incubation. The combined use of CDDP and TNF-alpha had synergistic effects on
      T98G and U87MG but not on U373MG and A172 cells. Sequential treatments showed
      that only pretreatment with CDDP for 2 h followed by TNF-alpha for 22 h was
      synergistic on cell cytotoxicity. Annexin V-flow cytometry and terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end-labeling assay showed that
      TNF-alpha can induce apoptosis in cells treated with CDDP. Although only
      sensitive cell lines express transcripts for p75 TNF receptor 2, changes in TNF
      receptors were not found to contribute to the susceptibility to TNF-alpha. The
      production of interleukin-6, a representative cytoprotective cytokine, from
      glioma cells stimulated by TNF-alpha was suppressed by the combined use of
      actinomycin D, but not CDDP. Our results indicate that CDDP can sensitize glioma
      cells to TNF-alpha-induced apoptosis by a mechanism other than blocking the
      cytoprotective protein production.

PMID- 11451201
TI  - The bleb formation of the extracellular pseudopodia; early evidence of
      microtubule depolymerization by estramustine phosphate in glioma cell; in vitro
      study.
AB  - Estramustine phosphate (EMP) is an anti-microtubule agent that depolymerizes
      microtubules and also causes apoptosis of glioma cells. Both of these
      pharmacological actions have been previously studied within the same cytotoxic
      range of EMP concentrations. The purpose of this study was to investigate which
      of these two phenomena occurred before the other. A preliminary MTT assay was
      done to distinguish non-cytotoxic (0.005-0.1 microM) and cytotoxic (0.5-10
      microM) of EMP for BT4C cells. To investigate apoptotic changes, transmission
      electron microscopy (TEM), DNA laddering, and in situ endo-labeling (TUNEL)
      method were employed. A chemotaxis assay was used to assess cell motility.
      Scanning electron microscopy and TEM immunocytochemistry with an anti-beta
      tubulin antibody were applied to detect morphological changes of the
      microtubules. Suppression of cell motility by cytotoxic doses of EMP (0.5-10
      microM) group was attributed by the cyto-reductive effect, relating to apoptosis.
      At 0.01-0.1 microM (non-cytotoxic doses), EMP did not indue apoptosis. At these
      concentrations, TEM and immunohistochemistry revealed the formation of blebs on
      the tip of the pseudopodia that contained abnormally depolymerized microtubules,
      a finding that was not observed at a low temperature or during cell migration.
      Cell chemotaxis was significantly inhibited by cytostatic EMP doses (0.05 and 0.1
      microM). Bleb formation of the pseudopodia might be evidence of the abnormal
      disassembly of microtubules by cytostatic EMP concentrations, prior to the
      induction of apoptosis. In glioma cells EMP probably initiates apoptosis by
      causing the depolymerization of microtubules. Inhibition of cell motility by
      cytostatic doses of EMP could be beneficial to support other therapies.

PMID- 11451202
TI  - Atypical teratoid/rhabdoid tumors in adult patients: case report and review of
      the literature.
AB  - Atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system are rare
      and extremely aggressive malignancies of early childhood. We report a case of
      AT/RT in an adult patient. A 30-year-old woman presented with headache, vomiting
      and ataxia during the second trimester of pregnancy. Magnetic resonance imaging
      revealed a posterior fossa mass. A gross total resection was performed.
      Pathological examination revealed an AT/RT. Despite the dismal prognosis the
      patient decided not to undergo an abortion. For this reason postoperative
      accelerated hyperfractionated radiotherapy was limited to the tumor region. Six
      months later the woman delivered a healthy baby. One week postpartum, a central
      nervous system recurrence localized apart from the primary lesion was treated
      with radiosurgery. Two months later a diffuse progression was noted. Despite a 6
      week course of oral temozolomide, the tumor progressed and the patient died 11
      months after diagnosis. Although survival was short, surgery and involved field
      radiotherapy yielded a progression-free interval of 9 months. This allowed the
      patient to carry pregnancy to term. Radiosurgery resulted in a complete remission
      of the first recurrence. Oral chemotherapy was not effective in controlling
      diffuse tumor spread.

PMID- 11451203
TI  - Intense p53 staining is a valuable prognostic indicator for poor prognosis in
      medulloblastoma/central nervous system primitive neuroectodermal tumors.
AB  - Intense p53 immunostaining may predict for a poor prognosis in central nervous
      system primitive neuroectodermal tumor of childhood. BACKGROUND: Medulloblastoma
      is a common childhood primary brain tumor. Potential prognostic indicators for
      patients with local disease are age, extent of resection, and gender. However,
      none of these are well established. Immunohistologic staining is a potentially
      useful means to identify high-risk patients. The purpose of this clinical
      pathologic study was to investigate the prognostic significance of GFAP,
      synaptophysin, Ki-67, and p53 immunostaining in medulloblastoma/central nervous
      system primitive neuroectodermal tumors (CNS PNETs.) MATERIALS AND METHODS: The
      records of 40 patients with CNS PNETs were reviewed. Their surgical specimens
      were immunostained for p53, glial fibrillary acidic protein (GFAP),
      synaptophysin, and Ki-67. The p53 specimens were scored blindly for the intensity
      of staining of nuclei (intense vs weak) and the quantity of cells stained. The Ki
      67, GFAP, and synaptophysin specimens were analyzed for quantity of cells
      stained. RESULTS: Ten patients' specimens stained intensely for the p53 protein.
      Eleven had weakly staining nuclei. Nineteen specimens had no staining. The
      patients with specimens that stained intensely had a statistically significant
      decreased disease free survival (P = 0.03). Mere presence or quantity of p53
      nuclear staining did not correlate with disease free survival.
      Immunohistochemical staining for Ki-67, GFAP, and synaptophysin did not correlate
      with disease free survival. Clinical parameters of age, gender, and extent of
      resection also did not approach statistical significance for disease free
      survival. CONCLUSION: Intense nuclear staining for p53 was the only variable in
      this clinical pathologic study that reached statistical significance for disease
      free survival. This suggests that intense staining for p53 may be the most
      important prognostic indicator for non-metastatic CNS PNETs. p53 Immunostaining
      with antibodies against p53 in CNS PNETs should be studied in a multi
      institutional setting with larger numbers of patients.

PMID- 11451204
TI  - Pleomorphic xanthoastrocytomas: immunohistochemistry, grading and clinico
      pathologic correlations. An analysis of 34 cases from a single Institute.
AB  - Pleomorphic xanthoastrocytomas (PXAs) are characterized as a well-delineated
      tumor entity with clear peculiarities in clinico-radiological picture,
      pathological appearance and biological behavior. Usually the PXAs are associated
      with relatively good prognosis. Nevertheless, up to 35% of patients die following
      one and more recurrence with or without tumor malignant transformation. Till now,
      there is no agreement on what histopathological features constitute to objective
      and reliable signs of PXAs malignancy and clinical outcome. Thirty-four PXAs were
      subdivided on three subsets: typical (Grade I) - tumors without mitoses per 20
      high power fields, proliferating (Grade II) tumors with mitoses but without
      necroses, and malignant (Grade III) - tumors with elevated mitotic index and
      necrotic foci. Also, immunohistochemical investigation with various tumor
      associated antigens was performed. All PXAs subtypes showed differences in
      clinical outcomes. There were no recurrences and death among the tumors Grade I.
      Five out of 14 (36%) Grade II PXAs have recurred and one of them died. All 5
      patients with PXAs Grade III have rapidly recurred and four of them died.
      Immunohistochemical variables, such as Ki-S1, p27/Kip1, vascular endothelial
      growth factor expression, p53 immunoreactivity and apoptotic index also exhibited
      significant differences among the three PXAs grades. The progression-free
      survival was significantly reduced for PXAs grade and presence of mitoses,
      whereas overall survival was reduced for mitotic index >or= 3 and presence of
      necroses. No one from immunohistochemical variables reached significant value. In
      summary, the three-tiered PXAs subdivision proposed by us is carrying some
      element of rationality but, undoubtedly, requires further prospective studies.

PMID- 11451205
TI  - White matter lesions and encephalopathy in patients treated for primary central
      nervous system lymphoma.
AB  - A retrospective analysis of the clinical presentations and neuroimaging
      characteristics of 33 patients with a primary central nervous system lymphoma
      (PCNL) who received cranial radiotherapy was performed to assess incidence of and
      risk factors for radiation-induced encephalopathy. CT and MRI scans were revised
      by a neurologist and a radiologist in conference. White matter abnormalities
      before and after radiotherapy on the last scan before recurrence were quantified
      according to a semi-quantitative scale. All available medical records were
      retrieved and reviewed with respect to demographic and tumor-related variables,
      treatment modalities, disease-free and overall survival and clinical symptoms and
      signs of encephalopathy. CT and MRI scans showed severe white matter lesions in
      75% of 20 patients and in 86% of patients aged more than 60 years. Forty percent
      of patients presented with new clinical signs of cognitive impairment a median of
      14.5 months after initial diagnosis (8.5 months after radiotherapy). The risk of
      white matter lesions appeared greater in patients aged >60 (RR 1.2, 95% CI = 0.8
      2.0), in patients with prior white matter lesions (RR 1.3, 95% CI = 0.8-2.1) and
      in patients with multifocal cerebral lymphoma (RR 1.5, 95% CI = 1.0-2.1). In
      conclusion, the risk of white matter lesions and clinical symptoms and signs of
      encephalopathy is high in patients treated by radiotherapy for PCNL. The risk
      appears to be greatest in older patients, patients with multifocal tumor and in
      those with prior white matter lesions on CT or MRI.

PMID- 11451206
TI  - Primary leptomeningeal lymphoma.
AB  - Primary leptomeningeal lymphoma is a rare disorder, and the neuroradiological
      characteristics or the complication of this rare disorder have not been well
      reported. We reported herein a patient with a primary leptomeningeal lymphoma who
      has complication with subdural hematoma. The patient complained of headache and
      vomiting. Neurological examination revealed progressive cranial nerve palsy.
      Cerebrospinal fluid examination disclosed monoclonal proliferation of atypical B
      lymphocytes. Cranial computed tomographic scans showed a left frontal mass with
      convex form to the brain parenchyma. T1-weighted magnetic resonance (MR) images
      disclosed subacute subdural hematoma. However, proton-weighted MR images showed
      high signal intensity in subarachnoid space, which suggested leptomeningeal
      lymphoma. He underwent craniotomy, and the diagnosis of leptomeningeal lymphoma
      complicated with subdural hematoma was confirmed. Systemic examinations disclosed
      no lymphomatous lesions except for leptomeningus, and the diagnosis of primary
      leptomeningeal lymphoma was established. We suggested that subdural hematoma was
      associated with primary leptomeningeal lymphoma in this patient. Cerebrospinal
      fluid examination and proton-weighted MR imaging should be performed when
      progressive neurological abnormalities are found in patients with subdural
      hematoma.

PMID- 11451207
TI  - Intramedullary spinal cord astrocytoma in adults: postoperative outcome.
AB  - Intramedullary spinal cord astrocytomas are relatively rare and usually low-grade
      lesions with a long natural history. The rarity of the condition and its indolent
      clinical course has made the evaluation of treatment efficacy difficult. To
      clarify postoperative outcome and prognostic factors, we performed a
      retrospective analysis of intramedullary spinal cord astrocytomas in a single
      institute. Twenty-eight patients were surgically treated between 1978 and 1999;
      of median age 36 years (range, 19-68 years); nineteen patients were males and
      nine females. All patients presented with pain and neurological deficits. The
      cervical cord was involved in fifteen patients, cervico-thoracic in five,
      thoracic in six and thoraco-lumbar in two. Gross total removal was performed in
      three patients, subtotal removal in six, partial removal in fourteen and biopsy
      only in five. Nineteen patients received radiation therapy postoperatively. The
      mean follow-up period was 31.9 months (range, 0.5-184 months). Low-grade
      astrocytomas were found in 18 cases, anaplastic astrocytoma in three cases and
      glioblastomas in seven cases. The median survivals of patients with low- and high
      grade astrocytoma were 184 months and 8 months, respectively (p < 0.05). The
      median survivals of irradiated and non-irradiated patients with low-grade
      astrocytoma were 184 months and 102 months. Neither the extent of resection, nor
      radiation influenced the survival rate. In summary, the histological grade was
      the most significant predictor of survival in patients with astrocytoma of the
      spinal cord.

PMID- 11451208
TI  - Folic acid.
AB  - Folic acid is an essential nutrient from the B complex group of vitamins. Folate,
      as a cofactor, is involved in numerous intracellular reactions, and this is
      reflected in the various derivatives that have been isolated from biological
      sources. Folic acid is involved in single carbon transfer reactions and serves as
      a source of single carbon units in different oxidative states. The processes
      involved in the absorption, transport, and intracellular metabolism of this
      cofactor are complex. Much of folate is bound tightly to enzymes, indicating that
      there is not excess of this cofactor and that its cellular availability is
      protected as well as being strictly regulated. In animals, the liver controls the
      supply of folate through first pass metabolism, biliary secretion, enterohepatic
      recirculation, as well as through senescent erythrocyte recycling. Deficiencies
      of folate can occur for many reasons, including reduced intake, increased
      metabolism, and/or increased requirements as well as through genetic defects. The
      effects of folate deficiency include hyperhomocysteinemia, megaloblastic anemia,
      and mood disorders. Folate deficiency has also been implicated in disorders
      associated with neural tube defects. Supplementation of grain products such as
      cereals has been undertaken in several countries as a cost-effective means of
      reducing the prevelance of neural tube defects. Recently, common polymorphisms
      have been discovered in several genes associated with folate pathways that may
      play a role in diseases associated with folate deficiency, particularly mild
      folate deficiency.

PMID- 11451209
TI  - Clinical uses of tumor markers: a critical review.
AB  - Tumor markers are molecules that indicate the presence of malignancy. They are
      potentially useful in cancer screening, aiding diagnosis, assessing prognosis,
      predicting in advance a likely response to therapy, and monitoring patients with
      diagnosed disease. Because of the low prevalence of most cancers in the general
      population and the limited sensitivity and specificity of available markers,
      these tests alone are generally of little value in screening for cancer in
      healthy subjects. Currently, however, PSA in combination with digital rectal
      examination and CA 125 together with ultrasound are undergoing evaluation as
      screening modalities for prostate and ovarian cancer, respectively. Again,
      because of a lack of sensitivity and specificity, markers are rarely of use in
      the early diagnosis of cancer. As prognostic indicators, markers may provide
      information that is independent of traditionally used factors or within subgroups
      defined by traditional criteria, for example, urokinase plasminogen activator in
      node-negative breast cancer. At present, the best available marker for predicting
      response to therapy is the estrogen receptor for selecting hormone-sensitive
      breast cancers. Many different markers can be used in the surveillance of
      patients with diagnosed malignancies, the most useful of these being HCG in
      trophoblastic disease and both AFP and HCG for nonseminomatous testicular germ
      cell tumors. In general, the currently available tumor markers lack sensitivity
      for early cancer and specificity for malignancy. The goal of future research
      should be to develop more sensitive and specific markers, especially for the
      common cancers.

PMID- 11451210
TI  - Relevance of clinical pharmacological models for the evaluation of therapeutic
      dose range of an AT1-receptor antagonist.
AB  - Clinical pharmacological models Antihypertensive drugs affecting the renin
      angiotensin system (RAS) can be evaluated in single-dose studies in healthy
      volunteers challenged with angiotensin I or II, or in subjects in whom the RAS
      has been activated by salt depletion. Such pharmacological studies can be used to
      investigate dose-response relationships. Objective The relevance of these models
      in predicting therapeutic dose range has been evaluated by comparing the results
      of pharmacological studies with those of a conventional dose-finding study in
      hypertensive patients with the new AT1-receptor antagonist olmesartan medoxomil.
      Results In healthy volunteers, 2.5-40 mg olmesartan medoxomil single doses
      significantly inhibited the pressor response to exogenous angiotensin I. A dose
      response relationship was observed, with relevant (> 75%) inhibition occurring at
      doses of 10 mg and above. In a single-dose crossover study in patients with mild
      to-moderate hypertension receiving a sodium-restricted diet, statistically
      significant lowering of mean 24-h blood pressure, measured by ambulatory blood
      pressure monitoring, was observed at doses of 10-80 mg. By comparison, a large
      scale (n = 792), placebo-controlled, dose-ranging study in patients with mild-to
      moderate hypertension likewise showed significant superiority over placebo for 10
      80 mg olmesartan medoxomil once-daily doses. Conclusion Single-dose clinical
      pharmacology studies provided an accurate indication of the effective dose range
      of a new AT1-receptor antagonist Such models can be useful in identifying, for
      more detailed study, the likely therapeutic dose range of new drugs acting on the
      RAS. However, the dose-response still requires testing in large target
      populations.

PMID- 11451211
TI  - The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk
      of clinically relevant drug interaction.
AB  - Orally administered olmesartan medoxomil was rapidly absorbed from the
      gastrointestinal tract and converted during absorption to olmesartan, the
      pharmacologically active metabolite that was subsequently excreted without
      further metabolism. The medoxomil moiety was released as diacetyl that was
      rapidly cleared by further metabolism and excretion. Peak plasma concentrations
      of olmesartan occurred 1-3 h after administration, after which concentrations
      decreased quickly. The elimination half-life was 10-15 h. Olmesartan medoxomil
      was not measurable in plasma and excreta. The volume of distribution was low,
      consistent with limited extravascular tissue distribution. Bioavailability (Cmax
      and area under the curve) increased approximately in proportion with dose, after
      single and multiple daily oral doses, over the therapeutic dose range (up to 40
      80 mg daily), above which systemic availability of olmesartan increased less than
      proportionally with increase in dose. Steady-state plasma concentrations of
      olmesartan were reached within the first few daily oral doses. On average,
      approximately 40% of systemically available olmesartan was excreted by the
      kidneys, the remainder being excreted in faeces, following secretion in bile.
      Renal clearance (0.5-0.7 l/h) was independent of dose, accounting for
      approximately 9-12% of an oral dose. The absolute bioavailability of olmesartan
      from olmesartan medoxomil tablets was 28.6%. Olmesartan exhibited little or no
      binding to blood cells. No clinically significant steady-state pharmacokinetic
      interactions were observed following co-administration of olmesartan medoxomil
      with digoxin, warfarin and aluminium magnesium hydroxide (antacid), supporting
      the low potential for clinically significant pharmacokinetic interactions to
      occur between olmesartan medoxomil and co-administered drugs.

PMID- 11451212
TI  - In vitro and in vivo pharmacology of olmesartan medoxomil, an angiotensin II type
      AT1 receptor antagonist.
AB  - Olmesartan medoxomil is a new non-peptide angiotensin (A) II antagonist under
      development for treating hypertension. It is a pro-drug containing an ester
      moiety that, after oral administration, is rapidly cleaved to release the active
      form olmesartan (RNH-6270). In vitro, olmesartan is a highly potent, competitive
      and selective All AT1 receptor antagonist with almost no antagonistic activity on
      AT2 and AT4 receptors. Olmesartan produces selective insurmountable inhibition of
      All-induced contractions of the guinea-pig aorta and is much more potent than
      losartan in reducing maximal responses. In vivo, intravenous olmesartan produces
      a rapid and long-lasting inhibition of All-induced pressor responses in conscious
      rats. Oral olmesartan medoxomil also inhibits All-pressor response but onset of
      the action is slower compared with intravenous administration. Following oral
      administration, olmesartan has a faster onset but similar potency when compared
      with candesartan cilexetil, and clearly exceeds losartan in both respects. Oral
      olmesartan medoxomil exhibits dose-dependent antihypertensive effects in several
      rat and dog models, with the most marked effects seen in high plasma renin
      models, when compared with normal or low renin types. Haemodynamic studies in
      spontaneously hypertensive rats and normotensive dogs showed intravenous
      olmesartan selectively reduces renal vascular resistance, which suggests that
      vasodilatation in the renal vascular bed contributes most to the antihypertensive
      action of the drug. Long-term treatment with olmesartan medoxomil exhibits,
      beside antihypertensive effects, beneficial effects in animal models of various
      types of nephrosis and heart failure, and anti-atherogenic effects in
      hyperlipidaemic animals. Olmesartan medoxomil is worthy of clinical development
      in essential and renal hypertension, particularly where renal function is
      threatened by underlying diabetic disease.

PMID- 11451213
TI  - Olmesartan medoxomil: influence of age, renal and hepatic function on the
      pharmacokinetics of olmesartan medoxomil.
AB  - Olmesartan medoxomil was rapidly absorbed and converted to olmesartan in elderly
      hypertensive patients, and in patients with renal and hepatic dysfunction. No
      olmesartan medoxomil itself was detected in plasma. Pharmacokinetic steady state
      was reached within the first few days after oral dosing. In elderly (65-75 years
      old), after 80 mg olmesartan medoxomil once daily, and very elderly (> or = 75
      years old) hypertensive patients after 10 mg daily, steady-state Cmax and area
      under the curve (AUC(0-24 h)) values were up to 44% higher compared with young
      patients (< 46 years). Steady-state elimination half-life values were also longer
      in elderly (12.8 h) and very elderly patients (16.5 h) compared with young
      patients (10.6 and 12.3 h, respectively). At steady state after 10 mg olmesartan
      medoxomil daily in patients with renal impairment, both Cmax and AUC(0-24 h)
      increased as creatinine clearance (CLCR) decreased, and renal clearance (CLR)
      decreased with decreasing CLCR. Steady-state Cmax and AUC(0-24 h) values in
      patients with mild (CLCR, 40-59 ml/min) and moderate (CLCR, 20-30 ml/min) were up
      to 39 and 82% higher than the values in healthy subjects. After single oral doses
      of 10 mg olmesartan medoxomil daily to patients with mild (Child-Pugh score < or
      = 6) and moderate (score 7-9) hepatic impairment, Cmax was generally similar to
      that in healthy matched subjects, but AUC increased by 30 and 48%, respectively,
      and was reflected in small increases in absolute bioavailability values compared
      with healthy subject controls. Excretion of olmesartan in urine also increased
      with the degree of hepatic impairment, indicating a compensatory excretion
      mechanism in this disease state. Since the increased plasma concentrations (Cmax
      and AUC(0-24 h)) in elderly and very elderly patients, and in mild and moderate
      renal and hepatic impairment, were several-fold lower than plasma concentrations
      observed in other studies after 80 mg olmesartan medoxomil daily that were well
      tolerated, a dosing adjustment in these groups is not considered necessary. In
      patients with severe renal impairment, however, consideration should be given to
      a lower starting dose, and it is recommended that the daily dose should not
      exceed 20 mg daily (compared with 40 mg daily for the general patient
      population).

PMID- 11451214
TI  - Blood pressure response, but not adverse event incidence, correlates with dose of
      angiotensin II antagonist.
AB  - OBJECTIVE: To assess the efficacy and safety of the novel angiotensin II
      antagonist olmesartan medoxomil in patients with mild to moderate essential
      hypertension, using a meta-analysis of the combined database from seven US and
      European clinical trials. DESIGN: Studies were randomized, double-blind, placebo
      controlled and dose-finding (2.5-80 mg), with treatment duration of 6-52 weeks.
      SETTING: Hospital outpatient clinics. PATIENT POPULATION: A total of 3,095
      patients in the safety population and 3,055 patients in the intent-to-treat
      (efficacy) population. METHODS: All studies used conventional sphygmomanometry
      for blood pressure measurements at trough (end of the dosing interval). Three
      studies also used 24-h ambulatory blood pressure monitoring for the principal
      efficacy evaluations. MAIN OUTCOME MEASURES: Percentage of patients achieving
      diastolic blood pressure (DBP) < or = 90 mmHg or decrease > or = 10 mmHg
      (responder rate), percentage of patients achieving a target DBP < or = 90 mmHg or
      target systolic blood pressure (SBP) < or = 140 mmHg (normalization rate), and
      mean decrease in DBP from baseline to last visit. RESULTS: Efficacy variables
      tended to be dose related up to the 40 mg dose level. All olmesartan medoxomil
      doses were statistically significantly more effective than placebo for responder
      rate, DBP and SBP normalization rates, and mean decrease in DBP. A clinically
      relevant decrease of > or = 5 mmHg from baseline in sitting DBP was also observed
      at doses of 20 mg and above after correction for placebo effect The safety
      profile of olmesartan medoxomil was similar to that of placebo and was not dose
      related. CONCLUSIONS: Olmesartan medoxomil was safe and highly effective in
      lowering blood pressure in patients with mild to moderate essential hypertension
      in these studies.

PMID- 11451215
TI  - Relative efficacy of an angiotensin II antagonist compared with other
      antihypertensive agents. Olmesartan medoxomil versus antihypertensives.
AB  - OBJECTIVE: To compare the relative efficacy and safety of olmesartan medoxomil
      (OM) with atenolol, captopril and losartan in phase III trials on mild to
      severely hypertensive patients. DESIGN: Multi-centre, randomized, double-blind,
      parallel group, with dose-titration studies lasting 12 or 24 weeks. METHODS: Two
      studies respectively compared 10 mg OM once daily (o.d.) with: (1) 50 mg atenolol
      o.d. in moderate to severe hypertensives receiving 25 mg hydrochlorothiazide o.d.
      over 12 weeks; and (2) 50 mg losartan o.d. in mild to moderate hypertensives over
      24 weeks, both with dose doubling at week4 if required. Study 3 compared 5 mg OM
      o.d. plus placebo o.d.with 12.5 mg captopril twice daily in mild to moderate
      hypertensives over 12 weeks, with dose doubling at weeks 4 and 8 if required. The
      primary outcome measure for all studies was the change from baseline to week 12
      in trough mean sitting diastolic blood pressure (DBP). Safety was monitored
      throughout all studies. RESULTS: (1) Atenolol and OM both reduced BP effectively
      in moderate to severe hypertensives. OM was significantly superior to: (2)
      losartan (95% confidence interval for baseline to week 12 change in DBP < 0,
      lower limit < -3.6 mmHg); and (3) captopril (95% confidence interval for baseline
      to week 12 change in DBP < 0, lower limit < -4.8 mmHg) in BP reduction for mild
      to moderate hypertensives. Treatment with OM was safe and well tolerated.
      CONCLUSION: At the doses tested, olmesartan medoxomil o.d. is as effective as
      atenolol, and more effective than both losartan and captopril in reducing blood
      pressure in the hypertensive population.

PMID- 11451216
TI  - Angiotensin II subtype 1-receptor antagonists in the treatment of diabetic
      nephropathy.
AB  - Diabetic nephropathy has become the leading cause of terminal renal failure in
      all Western nations due to a steady increase of patients with the renal
      complication of type 2 (non-insulin-dependent) diabetes mellitus. A number of
      modifiable risk factors have been identified that predispose to and/or accelerate
      renal disease in patients with diabetes mellitus. Among these, the level of blood
      pressure, even in the range of normotension according to World Health
      Organization or Joint National Committee definition, is closely related to the
      rate of progression of diabetic nephropathy. This has been documented in patients
      with incipient (microalbuminuric) and in patients with manifest (proteinuric)
      diabetic renal disease. Consequently, the treatment of even normotensive
      diabetics has been recommended once microalbuminuria is present, and blood
      pressure values in the low normal range should be aimed for. The selection of
      antihypertensive agents is also important, however, since a 'renoprotective
      effect' has been documented for drugs that interfere with the renin-angiotensin
      aldosterone system such as angiotensin converting enzyme inhibitors. Recently, a
      new class of drugs that selectively inhibits this system by specifically
      targeting the angiotensin II receptor has been developed. These angiotensin II
      subtype 1-receptor antagonists are efficacious antihypertensive agents with a
      side-effect profile similar to placebo. Evidence for a renoprotective effect in
      patients with diabetic nephropathy from a large controlled clinical trial is
      still awaited, but data generated in animal experiments and in smaller clinical
      trials are encouraging. Currently, these drugs are a valuable substitute for
      angiotensin converting enzyme inhibitors in patients who experience side effects
      such as intractable cough.

PMID- 11451217
TI  - Clinical potential: angiotensin converting enzyme inhibitor or angiotensin II
      antagonist?
AB  - Blockade of the renin-angiotensin system by angiotensin converting enzyme (ACE)
      inhibitors has an established role in the management of hypertension, heart
      failure, patients post-myocardial infarction and renal impairment. The mechanism
      of action of angiotensin II antagonists offers the potential of more complete
      blockade of angiotensin II, selective inhibition of the AT1 receptor and
      specificity for the renin-angiotensin system. Whether these mechanistic
      differences enhance the clinical potential of these drugs remains to be
      established. Preliminary evidence suggests that ACE inhibitors and angiotensin II
      antagonists have similar antihypertensive, haemodynamic and nephroprotective
      effects. Several major outcome trials with angiotensin II antagonists are
      underway and these should determine the eventual clinical potential of this
      class. Early results suggest equivalence with ACE inhibitors but further direct
      comparisons are needed. Angiotensin II antagonists have one undisputed advantage-
      excellent tolerability. Given the continuing under-use of ACE inhibitors because
      of concerns about adverse effects, this property alone may prove decisive in
      ensuring that angiotensin II antagonists yield the full clinical potential from
      blockade of the renin-angiotensin system.

PMID- 11451218
TI  - Eighth International Symposium on Biological and Environmental Reference
      Materials (BERM-8), Bethesda, MD, September 17-22, 2000. Proceedings.

PMID- 11451219
TI  - CRMs for the 21st century: new demands and challenges.
AB  - To play their role as essential tools for the achievement of comparability and
      traceability of measurements, the upcoming generation of certified reference
      materials will continue to be the subject of increased requirements related to
      their preparation, characterization, monitoring, documentation, and distribution.
      An analysis is made of the most important aspects not only related to the
      physical form of future CRMs, the determination of their shelf-life, and their
      certification, but also to increased requirements related to their distribution,
      including required additional documentation. Two examples of cost breakdown
      demonstrate the need for improved productivity of certification projects and more
      efficient marketing.

PMID- 11451220
TI  - Challenges from speciation analysis for the development of biological reference
      materials.
AB  - Starting with explanations for the increasing demand for speciation analysis the
      need of appropriate certified reference materials is justified. Specific aspects
      of biological reference materials for speciation QA/QC are discussed from the
      point of view of the total analytical process. Examples of unwanted species
      transformations during analysis are given and critical analytical steps are
      highlighted. Unchanged biological materials as CRMs and appropriate pure standard
      compounds are indispensable for the further development of this analytical field.

PMID- 11451221
TI  - Trends in certified reference materials for the speciation of trace elements.
AB  - The measurement of the chemical species of elements (instead of the total element
      concentration) has become an irreversible trend in analytical chemistry. The
      motivation lies in the fact that the biochemical and geochemical behaviour of an
      element is governed by its species. Quality assurance of the analytical
      procedures used for speciation analysis requires the analysis of representative
      reference materials, certified for the relevant species. Up to now the number of
      existing certified reference materials for trace element species is very limited.
      The most important ones are environmental CRMs certified for trialkyltin
      compounds, methylmercury, Cr(III)/Cr(VI) and food CRMs certified for arsenic
      species and methylmercury. Major developments are to be expected in CRMs focussed
      on environmental problems, including waste treatment, on bioavailability of trace
      elements in food and on bio-monitoring in occupational health and hygiene. It is,
      however, unlikely that the producers of CRMs will ever be able to cover all
      needs. Add to this that many, very active species are notoriously unstable and/or
      short living and require in-situ analysis. This will lead to different analytical
      developments, such as analyses in-situ, where the classical concept of CRMs may
      not stand firm anymore.

PMID- 11451222
TI  - Some difficult problems still existing in the preparation and certification of
      CRMs.
AB  - Differences between particle size measurements of CRMs by various methods are
      discussed and the importance of the reliability of such data for proper
      estimation of the homogeneity of the material is emphasized. On the basis of a
      very simple model, the dependence of the Ingamells' sampling constant on the
      average mass of a single particle of the material is derived, and theoretical
      predictions are compared with the experimental results. Various approaches to the
      certification of the candidate RMs are briefly reviewed. The merits of the
      approach being used in this laboratory to evaluate data obtained in the
      interlaboratory comparison, and to assign certified and information values, is
      discussed. The conclusions are supported by results obtained for selected trace
      elements by use of "definitive" (primary) and "very accurate" methods. Some
      observations on the unusual resistance of some biological materials to wet ashing
      and the resulting possibility of making analytical errors are mentioned.

PMID- 11451223
TI  - What's new with the NRC certified reference material program.
AB  - The environmental CRMs currently available from NRC Ottawa comprise four natural
      waters for trace elements, four biological tissues for trace elements and
      methylmercury, three marine sediments for major and trace elements (one sediment
      has certified values for butyltins) and one fish tissue for organochlorines
      (PCBs, dioxins). Although significant effort has been expended to maintain this
      suite of materials, several new initiatives have also recently been completed or
      are in progress. The certified value for arsenobetaine in Dogfish Muscle CRM DORM
      2 has been established. The certification approaches, as well as the studies to
      determine extraction efficiency of this organoarsenic compound, are presented. A
      stability study has been completed for Hg in a natural water sample and plans are
      underway for production of a CRM. Assessment of micronutrient stability in
      seawater for the purposes of CRM production is continuing and progress on this
      initiative is discussed.

PMID- 11451224
TI  - Recent developments in the field of environmental reference materials at the JRC
      Ispra.
AB  - The production of reference materials for environmental analysis started in the
      Joint Research Centre at Ispra/Italy in 1972 with the objective of later
      certification by the BCR, but for obvious budget reasons only a fraction of the
      total production achieved at Ispra ever reached certification level, although all
      materials were produced according to the severe quality requirements requested
      for certified reference materials. Therefore, the materials not destinated to
      certification are in growing demand as inter-laboratory test materials and as
      laboratory reference materials, for internal quality control, e.g., by control
      charts. The history of reference material production within the Joint Research
      Centre is briefly reviewed and the latest additions described. New developments
      such as micro-scale reference materials intended for analytical methods requiring
      sample intakes at milligram or sub-milligram level and therefor not finding
      supply on the reference material market, and "wet" environmental reference
      materials, which meet more precisely the "real-world" environmental analysis
      conditions, are presented and the state-of-the-art discussed.

PMID- 11451225
TI  - Recent production of candidate reference materials at IRMM.
AB  - In the execution of its mission to promote a common European measurement system
      in support of EU policies, IRMM's Reference Materials Unit is currently involved
      in preparation of proficiency-testing samples and candidate reference materials.
      Recent work related to bovine spongiform encephalopathy in cows, genetically
      modified organisms, and a variety of environmental materials is described.

PMID- 11451226
TI  - The use of spectro(photo)metric reference materials in chemical metrology-
      present status in Romania.
AB  - This paper discusses some aspects of the use of certified reference materials
      (CRMs) to ensure the uniformity of results, especially through calibration and
      validation of spectro(photo)metric instrument performance. In this way the link
      between the intrinsic performance of instruments and the accuracy of measurement
      results is underlined. Some types of local CRM are also presented.

PMID- 11451227
TI  - Reference materials and certified reference materials for spectrometry in
      Romania.
AB  - Several reference materials (RMs) and certified reference materials (CRMs) are
      widely used in Romania as measurement standards in different spectrochemical
      measurements. Among them, single element standard solution certified for their
      mass concentration play a key role in ensuring the required traceability of
      results expressed in this measurement unit. A short review of the locally
      available elemental RMs and CRMs used in atomic spectrometry or in other
      analytical techniques where aqueous standard solutions are required (usually
      called RMs or CRMs for spectrometry) is given. The experience of the INM in
      preparation and certification of such materials is described. Some aspects
      regarding their use for ensuring the accuracy and for confirmation of the
      traceability of analytical measurements, especially through calibration and
      metrological validation of main instrument performances, are discussed.

PMID- 11451228
TI  - Biological and environmental reference materials in CENAM.
AB  - Since 1994, when the NIST/NOAA Quality Assurance Program in Chemical Measurements
      was discussed in Queretaro, CENAM, the National Measurement Institute (NMI) of
      Mexico, has become involved in the development of reference materials. In the
      field of biological and environmental reference materials, in particular, the
      NORAMET collaboration program with NIST and NRC, and the North-American
      Environmental Cooperation signed among three free-trade treaty organizations,
      have greatly helped the development of the materials metrology program in the
      newly established CENAM. This paper describes some particularly significant
      efforts of CENAM in the development of biological and environmental reference
      materials, on the basis of inter-comparison studies organized with local and
      governmental environmental agencies of Mexico. In the field of water pollution
      CENAM has developed a practical proficiency testing (PT) scheme for field
      laboratories, as a part of registration by local government in the metropolitan
      area, according to the Mexican Ecological Regulation. The results from these
      eight PTs in the last 5 years have demonstrated that this scheme has helped
      ensure the reliability of analytical capability of more than 50 field
      laboratories in three states, Mexico, D.F., and the States of Mexico and
      Queretaro. Similar experience has been obtained for more than 70 service units of
      stack emission measurements in the three states in 1998 and 1999, as a result of
      the design of a PT scheme for reference gas mixtures. This PT scheme has been
      accomplished successfully by 30 analytical laboratories who provide monitoring
      services and perform research on toxic substances (Hg, methylmercury, PCB, etc.)
      in Mexico. To support these activities, reference samples have been produced
      through the NIST SRMs, and efforts have been made to increase CENAM's capability
      in the preparation of primary reference materials in spectrometric solutions and
      gas mixtures. Collaboration among NMIs has also successfully overcome the
      inability of CENAM to prepare biological tissue for mercury assessment and marine
      sediments for analysis of trace metals. The importance of international
      collaboration is stressed not only in the NORAMET region but also in the SIM, to
      provide help for each other and achieve mutual recognition among member countries
      of the region.

PMID- 11451229
TI  - Reference materials--a view from a small country.
AB  - ISO/IEC 17025 has an increased emphasis on traceability and estimation of
      uncertainty of measurement compared with ISO Guide 25. Demonstration of
      traceability is a new concept in analytical chemistry and depends on access to
      relevant reference materials or use of reference methods. Until now most
      reference materials used in New Zealand have been imported, because they offered
      international comparability. New Zealand is currently starting to develop the
      required infrastructure so that it will be able to produce unique reference
      materials that will contribute to the total international effort in improving the
      reliability of analytical chemistry.

PMID- 11451230
TI  - The deplorable state of the description of the use of certified reference
      materials in the literature.
AB  - A detailed survey of 26 scientific journals showed that journal editors and a
      majority of authors of the re- c viewed papers seem unconcerned by the importance
      of  correctly reporting their use of certified reference materials (CRMs). Only
      around 55% of the abstracts surveyed mention the use of CRMs described in these
      papers. This, however, is of key importance as the abstract of a paper is most
      widely available in electronic media. Many authors mentioned the use of CRMs in
      passing, often in incomplete form and without giving any details of the results
      obtained. Some are confused about the source of the reference material used, as
      they fail to report the type or the producer of CRMs applied. Others use
      materials that do not match the samples analyzed or do not see the need to use
      any CRM, despite the availability of suitable materials. Even in cases where
      correct data were given for type and producer of the CRMs, frequently the proper
      use and statistical evaluation are questionable. To improve this situation it is
      necessary that publishers should give recommendations where and how the use of
      CRMs should be described.

PMID- 11451231
TI  - Some aspects of the evaluation of measurement uncertainty using reference
      materials.
AB  - To ensure and to confirm the required traceability according to the definition
      given in the International Vocabulary of Basic and Standard Terms in Metrology,
      three main aspects need to be considered in practice: "stated reference",
      "unbroken chain of calibration" and "stated uncertainty". For a certain
      spectrochemical result, each of the aspects above mentioned is highly dependent
      on measurement uncertainty, both on its magnitude and how it was estimated. The
      paper describes the experience of the Romanian National Institute of Metrology
      (INM) in estimating measurement uncertainty during certification of reference
      materials, in metrological calibration and during specific analytical processes.
      Practical examples of the use of reference materials or certified reference
      materials issued by the INM to estimate measurement uncertainty are discussed for
      their applicability in spectrochemical and turbidity analysis. Some aspects of
      the use of analysis of variance (ANOVA) to obtain additional information on the
      components of measurement uncertainty and to identify the magnitude of individual
      random effects are presented.

PMID- 11451232
TI  - Evaluation of results derived from the analysis of certified reference materials-
      a user-friendly approach based on simplicity.
AB  - Certified reference materials (CRMs) have now been in regular use for several
      decades. Their production and certification are regulated by international
      standards. But, even today there are no agreements on procedures for evaluating
      results obtained by the users. As a consequence, the way CRM results are treated
      in the literature leaves a lot to be desired. A statistical evaluation is rarely,
      if ever, described in published reports. The most common approach is to compare
      the found mean and/or range with the certified range and then state if the mean
      falls within the certified range, or if the two ranges overlap. If this happens,
      the analyst is usually satisfied. In addition, usually no regard is paid to the
      fact that the certified interval is based on a 95% confidence interval (CI) and
      the found interval on standard deviation and that this evaluation has little, if
      any, statistical relevance. Long-term evaluation of a CRM often consists in
      nothing more than producing a control chart, which relates the found results to
      the certified mean and CI. This paper is an attempt to improve the situation by
      providing a set of easy-to-use guidelines for evaluating results from CRMs.
      During the process we have identified different areas in which there is a need
      for such guidelines: 1. short-term evaluation of a single, or multiple,
      determination at one or several specific times; 2. identification of systematic
      and random errors; 3. evaluation of CRMs when used in a collaborative trial of a
      method; and 4. long-term evaluation for monitoring an analytical process over
      extended periods of time. It is important that the guidelines do not require
      expert competence in statistics from the analyst. Such obstacles would probably
      render most guidelines unused.

PMID- 11451233
TI  - Estimating the uncertainty of stability for matrix CRMs.
AB  - The new version of ISO Guide 34 requires producers of certified reference
      materials (CRMs) to include contributions of possible instability to the overall
      CRM uncertainty, to obtain a value for the uncertainty in compliance with the
      Guide to the Expression of the Uncertainty in Measurement (GUM). A pragmatic
      approach to estimating the uncertainty of stability is presented. It relies on
      regression analysis of stability data with subsequent testing of the slope of the
      regression line for significance. If the slope is found to be statistically
      insignificant, a shelf life is chosen and the uncertainty connected with this
      time is estimated via the standard deviation of the slope. This uncertainty is
      included in the overall uncertainty of the CRM. This approach is explained with
      examples showing its applicability to matrix CRMs.

PMID- 11451234
TI  - Water as a source of errors in reference materials.
AB  - In the field of reference materials, long-term stability is of highest
      importance. Particularly for biological matrices, any kind of deterioration must
      be avoided during shelf-life. In the production precautions are taken to prevent
      these, but possible alterations caused by intensive drying have been
      underestimated until today. This presentation discusses several mechanisms of
      deterioration related to water activity and water content. Comparison of the
      results for water and moisture for six reference materials and their water
      sorption isotherms serve as a base to discuss the importance of accurate dry mass
      corrections for certified values. It is shown that the method chosen for dry mass
      correction influences certified contents significantly and a method description
      must be given. Furthermore, it is confirmed that for biological matrices optimal
      ranges of water activity and water content exist, where hygroscopicity is low
      without significant danger of product deterioration. Additionally, handling is
      facilitated in the optimised ranges.

PMID- 11451235
TI  - GC-FID as a primary method for establishing the purity of organic CRMs used for
      drugs in sport analysis.
AB  - The National Analytical Reference Laboratory has synthesized and characterized 67
      anabolic steroid marker metabolites, both unlabelled and deuterated, and 37 key
      glucuronide and sulfate steroid conjugate pure substance reference materials.
      Work is also in process to establish their full traceability so that they can be
      issued as certified and primary reference materials. Both identity and purity
      have been rigorously characterized using a number of techniques and a primary
      method for purity assessment developed, based gas chromatography combined with
      flame ionization detection for the parent steroids and HPLC with evaporative
      light scattering detection for non-volatile steroid conjugates. Strategies for
      establishing traceability and for estimating measurement uncertainty are
      reported. The strategies described are considered applicable to a wide range of
      organic pure substance reference materials.

PMID- 11451236
TI  - Reference materials at emission levels of NH3 and HCl.
AB  - Due to instability in static mixtures, in the past only dynamic preparation
      techniques for mixtures of NH3 and HCl were maintained; however, recent
      developments of new passivation techniques for cylinder treatment and
      commercially available nitrogen with a very low content of impurities have opened
      up the possibility of preparing stable mixtures in cylinders by gravimetry.
      Mixtures of NH3 (300 microL/L and 30 microL/L) and HCI (300 microL/L) were
      prepared in nitrogen in cylinders with different passivation treatments. The
      mixtures were compared with dynamically prepared mixtures using Photo Acoustic
      detection (PAS) and FT-IR. The uncertainty is about 3.5% with PAS analysis for
      NH3 at the 300 microL/L level. For the analysis of HCI with FT-IR the initial
      uncertainty in the 300 microL/L mixtures is about 7%. Two of the HCI mixtures
      show significant instability; for the other three mixtures the uncertainty in the
      measurement is too large to discriminate between stability and instability. The
      NH3/N2 mixtures are stable within 3.5% for a one-year period. The stability of
      the 30 microL/L mixtures of NH3 cannot be underpinned by measurement results, but
      a systematic effect in the measurement procedure seems more likely than
      instability. Improvement in the measurement procedure should clarify this point.

PMID- 11451237
TI  - Database of natural matrix reference materials (NMRM) for organic constituents.
AB  - The International Atomic Energy Agency maintains a database of internationally
      available certified reference materials (CRM) of natural matrices. This database
      is periodically updated, and presently documents nearly 25,000 measurands in
      1,700 materials. The organic constituents are classified in five major groups of
      analytes aliphatic and aromatic hydrocarbons (A), chlorinated hydrocarbons (B),
      pesticides (C), organometallic compounds (D) and other organic constituents
      (nutrients, etc.) (E). The matrices include natural materials such as body
      fluids, food products, soils, and sediments, terrestrial (e.g. plants), and
      anthropogenic products (e.g. dust, fly ash). These five organic groups of
      analytes encompass more than 2000 measurands for 420 different analytes in 230
      materials. Of these measurands, 1,682 (68%) are certified, and 768 (32%) are
      provided as informational values. Within each major group of analytes, measurands
      reported as informational values accounted for: A (35%); B (35%); C (26%); D
      (10%), and E (22%). The high proportion of informational values (i.e. non
      certified values) for A, B, and C, compares well with a similar but undesirable
      situation faced in the nineteen-seventies in the inorganic area when simultaneous
      multielement techniques became available. In the case of D and E, it appears that
      mostly targeted analytes are measured, leading to a cohesive certification
      profile. Although the IAEA database is not equally comprehensive for all groups
      of analytes cited above, it can still serve as an useful indicator of the status
      of organic constituents in RMs.

PMID- 11451238
TI  - Development of a reference material for routine performance monitoring of methods
      measuring polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and
      dioxin-like polychlorinated biphenyls.
AB  - Matrix-matched environmental certified reference materials (CRMs) are one of the
      most useful tools to validate analytical methods, assess analytical laboratory
      performance and to assist in the resolution of data conflicts between
      laboratories. This paper describes the development of a lake sediment as a CRM
      for polychorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans
      (PCDFs) and dioxin-like polychlorinated biphenyls (DLPCBs). The presence of
      DLPCBs in the environment is of increased concern and analytical methods are
      being developed internationally for monitoring DLPCBs in the environment. This
      paper also reports the results of an international interlaboratory study
      involving thirty-five laboratories from seventeen countries, conducted to
      characterize and validate levels of a sediment reference material for PCDDs,
      PCDFs and DLPCBs.

PMID- 11451239
TI  - A review of the DNA standard reference materials developed by the National
      Institute of Standards and Technology.
AB  - The Standard Reference Materials Program at the US National Institute of
      Standards and Technology (NIST) has three human DNA standard reference materials
      (SRM 2390, SRM 2391a, and SRM 2392) currently available [1, 2]. Both the DNA
      profiling SRM 2390 and the polymerase chain reaction (PCR)-based DNA profiling
      SRM 2391a are intended for use in forensic and paternity identifications, for
      instructional law enforcement, or for non-clinical research purposes and are not
      intended for clinical diagnostics. The mitochondrial DNA (mtDNA) SRM 2392 is to
      provide standardization and quality control when performing PCR and sequencing
      any segment or the entire 16,569 base pairs that comprise human mitochondrial
      DNA. SRM 2392 is designed for use by the forensic, medical, and toxicological
      communities for human identification, disease diagnosis or mutation detection.

PMID- 11451240
TI  - EUROSOILS--a set of CRMs for comparability of soil-measurements.
AB  - An overview is given on the development, properties, and application of the
      European reference soil set--the EUROSOILS. The introduction of this new type of
      reference material has, for the first time, enabled comparison of data related to
      the interaction of chemical substances with the soil, and thus, improvement of
      soil quality. Because of their unforeseen success, a second generation of
      EUROSOILS had been produced and the range of application extended to other types
      of measurement related to the soil matrix--soil pH, carbon and nitrogen content,
      particle-size distribution and cation-exchange capacity. Other fields of
      application include analytical method development or testing of soil
      decontamination techniques. On the basis of the success of the EUROSOIL concept
      and the need for a common basis for comparison of soil-related data in Europe and
      beyond, the European Commission's Institute for Reference Materials and
      Measurements decided to certify several properties of the second EUROSOIL
      generation, thus establishing a common QA/ QC system for soil-related data. The
      main features of the EUROSOILS, their origin, the necessary field and laboratory
      work, and some interesting background information about the project are presented
      in this paper.

PMID- 11451241
TI  - Harmonized protocol and certified reference material for the determination of
      extractable contents of phosphorus in freshwater sediments--a synthesis of recent
      works.
AB  - An analytical protocol for the determination of the extractable phosphorus
      contents in freshwater sediments has been harmonized through interlaboratory
      studies in the frame of the Standards Measurements and Testing Program of the
      European Commission. A homogeneous and stable sediment reference material has
      been prepared and certified on the basis of this protocol named SMT protocol, and
      will be available in spring of 2001. The SMT protocol, together with the
      reference material, are useful tools in the field of water management, especially
      at a time when quality assurance and data comparability are of paramount
      importance in laboratory analysis. The knowledge of the bioavailable forms of
      phosphorus is important not only for sediments but also for sludge and soils.
      Therefore, the SMT protocol could be extended to these materials and new CRMs
      could be prepared. The SMT protocol was used in a study of a reservoir, which
      allowed to calculate the P stock, therefore helping to predict the restoration
      delay of the lake. The paper describes the protocol and the CRM, and gives a
      brief outline of the case study.

PMID- 11451242
TI  - Preparation and characterization of a set of IAEA reference air filters for
      quality control in air-pollution studies.
AB  - Several sets of reference air filters were prepared as part of an IAEA evaluation
      of the performance of laboratories involved in air-pollution studies. Each set
      comprised three polycarbonate membrane filters, two of which were loaded with
      urban air particulate matter (APM) obtained in Vienna or Prague, and one unloaded
      filter. The filters were loaded by filtration of a suspension of the APM
      materials in water. The homogeneity both of bulk APM materials and of the loaded
      filters was evaluated and found suitable by determining several elements by
      instrumental neutron-activation analysis (INAA), proton-induced X-ray emission
      (PIXE), and micro-X-ray energy-dispersive fluorescence analysis (micro-EDXRF).
      After evaluation of the homogeneity, INAA, PIXE, EDXRF, atomic absorption
      spectrometry (AAS), inductively coupled plasma optical emission spectrometry (ICP
      OES), and ICP mass spectrometry (ICP-MS) were used to characterize the filter
      materials and establish "target values" and their associated standard deviations
      for 15 elements. Problems encountered during the preparation of these unique,
      simulated air filters and the criteria for setting both the target values and
      standard deviations are presented.

PMID- 11451243
TI  - An alternative method for the certification of the sulfur mass fraction in coal
      Standard Reference Materials.
AB  - The S mass fractions of coal SRMs 2682b, 2684b, and 2685b are certified by direct
      comparison with coal SRMs 2682a, 2684a, and 2685a, respectively, using high
      temperature combustion analysis with infrared (IR) absorption detection. The S
      mass fractions of the "a" materials used for calibration were previously
      determined by means of isotope-dilution thermal-ionization mass spectrometry (ID
      TIMS). Therefore, the comparisons performed with the combustion-IR absorption
      method establish direct traceability links to accurate and precise ID-TIMS
      measurements. The expanded uncertainties associated with the certified S mass
      fractions are of approximately the same magnitude as would be expected for the ID
      TIMS methodology. An important aspect of these certifications is that each "b"
      material is essentially identical with the corresponding "a" material, because
      both were produced from the same bulk, homogenized coal. As a test of the
      efficacy of the new certification approach when calibrant and unknown are not
      identical, the S mass fraction of coal SRM 2683b has been determined by direct
      comparison to coal SRM 2683a. These two coals, which have both previously been
      analyzed with ID-TIMS, are different in terms of S content and other properties.
      Whereas the S mass fraction for SRM 2683b determined with the new methodology
      agrees statistically with the ID-TIMS value, there is reason for caution in such
      cases. In addition to the usefulness of the alternative approach for
      certification activities within NIST, this approach might also be an excellent
      way of establishing NIST traceability during the value assignment process for
      reference materials not issued by NIST. Further research is needed, however, to
      understand better the scope of applicability.

PMID- 11451244
TI  - Possibilities of low-level determination of silicon in biological materials by
      activation analysis.
AB  - The capabilities of neutron and photon activation analysis (NAA and PAA,
      respectively) for low-level determination of silicon in biological materials have
      been examined. Sensitivities of a variety of modes of NAA and PAA with
      radiochemical separation have been evaluated. Results are presented for silicon
      in reference materials CSRM 12-2-03 Lucerne, Bowen's Kale, NIST SRM-1571 Orchard
      Leaves, and NIST SRM-1515 Apple Leaves. The results were obtained by employing
      the 29Si(n,p)29Al reaction with fast reactor neutrons and the radiochemical
      procedure developed for aluminium separation. Possibilities of further
      improvement of the silicon determination limit down to the microg g(-1) level by
      employing NAA and PAA with radiochemical separation are outlined.

PMID- 11451245
TI  - Determination of silicon in biological samples by ICP-OES after non-oxidative
      decomposition under alkaline conditions.
AB  - A non-oxidative alkaline sample digestion procedure using tetramethylammonium
      hydroxide and a high pressure, microwave assisted autoclave digestion system was
      developed. The silicon concentrations of the digested samples were measured by
      inductively coupled axial plasma optical emission spectrometry (ICP-OES). Details
      of the digestion conditions as well as the optimised instrumental parameters for
      ICP-OES are described. The method was developed and tested using silicon-spiked
      ascorbic acid and applied to samples of animal tissue and organs. The total
      silicon content of two different reference materials, NIST 1577b Bovine liver and
      BCR 184 Bovine Muscle having neither certified nor informational values for Si
      was determined. The results obtained are compared with the results of independent
      methods such as wavelength dispersive x-ray fluorescence spectrometry (WDXRF) and
      solid sampling electrothermal atomic absorption spectrometry (ETAAS). The method
      described achieves a limit of detection of 2 mg kg(-1) using 100 mg of solid
      biological or organic material and covers a concentration range of up to 500 mg
      kg(-1).

PMID- 11451246
TI  - Methodologies for the analysis of rare earth elements and their relevance to
      reference materials.
AB  - India has the third largest resources of rare earth elements (REE) in the world.
      These resources are essentially the monazite sand present in the beaches of
      southwest, south-east, and mid-eastern coasts of India. Therefore, analytical
      methodologies for the determination of REE in sea water and high-purity materials
      were developed. An overview of this work and its relevance to the preparation of
      standard reference materials of REE in sea water, marine sediments, and high
      purity materials in the future is given.

PMID- 11451247
TI  - k0-NAA, a valuable tool for reference-material producers.
AB  - The main concern of producers of certified reference materials (CRM) is the
      preparation of high-quality products with demonstrated homogeneity and stability,
      combined with a well established set of certified characteristics. CRM producers
      must, furthermore, comply with other constraints imposed by the ISO Guide 34:
      production processes, production control, and certification analyses should be
      performed by expert laboratories, using validated protocols documented in their
      respective quality assurance manuals; laboratory mean values and the
      corresponding "expanded" uncertainties, must be used for the determination of the
      certified values, as recommended by the ISO Guide to the Expression of
      Uncertainties in Measurements (GUM); and when possible, traceability of the
      certified value to the SI units, using appropriately validated and/or primary
      methods, must be ensured. k0-NAA, i.e. neutron activation analysis with k0
      standardization, is one of the analytical techniques implemented at the Reference
      Material Unit of IRMM; it meets the first two requirements.

PMID- 11451248
TI  - Using inductively coupled plasma-mass spectrometry for calibration transfer
      between environmental CRMs.
AB  - Multielement analyses of environmental reference materials have been performed
      using existing certified reference materials (CRMs) as calibration standards for
      inductively coupled plasma-mass spectrometry. The analyses have been performed
      using a high-performance methodology that results in comparison measurement
      uncertainties that are significantly less than the uncertainties of the certified
      values of the calibration CRM. Consequently, the determined values have
      uncertainties that are very nearly equivalent to the uncertainties of the
      calibration CRM. Several uses of this calibration transfer are proposed,
      including, re-certification measurements of replacement CRMs, establishing
      traceability of one CRM to another, and demonstrating the equivalence of two
      CRMs. RM 8704, a river sediment, was analyzed using SRM 2704, Buffalo River
      Sediment, as the calibration standard. SRM 1632c, Trace Elements in Bituminous
      Coal, which is a replacement for SRM 1632b, was analyzed using SRM 1632b as the
      standard. SRM 1635, Trace Elements in Subbituminous Coal, was also analyzed using
      SRM 1632b as the standard.

PMID- 11451249
TI  - Direct and precise determination of environmental radionuclides in solid
      materials using a modified Marinelli beaker and a HPGe detector.
AB  - A simple but precise detection method was studied for the determination of
      natural radionuclides using a conventional HPGe detector. A new aluminium beaker
      instead of a plastic Marinelli beaker was constructed and examined to reach
      radioactive equilibrium conditions between radon and its daughter elements
      without the escape of gaseous radon. Using this beaker fifteen natural
      radionuclides from three natural decay series could be determined by direct gamma
      ray measurement and sixteen radionuclides could be determined indirectly after
      radioactive equilibrium had been reached. Analytical results from ground water
      were compared with those from conventional alpha spectroscopy and the results
      agreed well within 12% difference. Nitrogen gas purge was used to replace the
      surrounding air of the detector to obtain a stable background and reducing the
      interference of radon daughter nuclides in the atmosphere. The use of nitrogen
      purging and the aluminium Marinelli beaker results in an approximately tenfold
      increase of sensitivity and a decrease of the detection limit of 226Ra to about
      0.74 Bq kg(-1) in soil samples.

PMID- 11451250
TI  - NH4NO3 extractable trace element contents of soil samples prepared for
      proficiency testing--a stability study.
AB  - In view of its intended use as a sample for proficiency testing or as a reference
      material the stability of the extractable trace element contents of a soil from
      an irrigation field was tested using the extraction with 1 mol/L ammonium nitrate
      solution according to DIN 19730. Therefore, changes of the extractability of
      sterilized and non sterilized soil samples stored at different temperatures were
      evaluated over a period of 18 months. Sets of bottles were kept at -20 degrees C,
      +4 degrees C, about +20 degrees C and +40 degrees C, respectively. The NH4NO3
      extractable contents of Cd, Cr, Cu, Ni, Pb and Zn were determined immediately
      after bottling and then after 3, 6, 12 and 18 months with ICP-AES or ETAAS.
      Appropriate storage conditions are of utmost importance to prevent deterioration
      of soil samples prepared for the determination of NH4NO3 extractable trace
      element contents. Temperatures above +20 degrees C must be avoided. The observed
      changes in the extractability of the metals (especially for Cr and Cu) most
      likely could be related to thermal degradation of the organic matter of the soil.
      There is no need to sterilize dry soil samples, because microbiological activity
      in soils with a low moisture content appears to be negligible with regard to
      trace element mobilization.

PMID- 11451251
TI  - Recent developments in food-matrix Reference Materials at NIST.
AB  - Since 1996, the National Institute of Standards and Technology (NIST) has
      developed several food-matrix Standard Reference Materials (SRMs) characterized
      for nutrient concentrations. These include SRM 1544 Fatty Acids and Cholesterol
      in a Frozen Diet Composite, SRM 1546 Meat Homogenate, SRM 1548a Typical Diet, SRM
      1566b Oyster Tissue, SRM 1846 Infant Formula, and SRM 2383 Baby Food Composite.
      Three additional materials--SRM 1946 Lake Superior Fish Tissue, SRM 2384 Baking
      Chocolate, and SRM 2385 Spinach--are in preparation. NIST also recently assigned
      values for proximate (fat, protein, etc.), individual fatty acid, and total
      dietary fiber concentrations in a number of existing SRMs and reference materials
      (RMs) that previously had values assigned for their elemental composition. NIST
      has used several modes for assignment of analyte concentrations in the food
      matrix RMs, including the use of data provided by collaborating laboratories,
      alone and in combination with NIST data. The use of data provided by
      collaborating food industry and contract laboratories for the analysis of food
      matrix RMs has enabled NIST to provide assigned values for many analytes that
      NIST does not have the resources or analytical expertise to measure.

PMID- 11451252
TI  - Twenty five years of reference material activity at Agriculture and Agri-Food
      Canada.
AB  - In the mid 1970s, the available RMs, notably Bowen's Kale and Orchard Leaves and
      Bovine liver from National Bureau of Standards (NBS), although of great benefit,
      were overwhelmingly insufficiently representative, in respect of matrix and
      elemental composition, of the wide range of natural products submitted for
      analysis and in worldwide commerce. To provide additional coverage, an RM
      development project was initiated with input from cooperating analysts leading to
      an Agriculture and Agri-Food Canada/National Institute of Standards and
      Technology (NIST) cooperative venture and development of a total of 12 different
      agricultural/food RMs. With a total of 303 concentration values for 34 elements
      and a wide range of matrix components such as ash, silica, protein, fat,
      carbohydrate and fiber, these RMs significantly augment the world repertoire of
      biological control materials. A final material under consideration is a highly
      reliable, discrete, synthetic RM for quality control and calibration. This paper
      summarizes the research and developmental activities undertaken during the past
      quarter of a century related to RM development at Agriculture and Agri-Food
      Canada and includes a short historical background, conceptual considerations,
      preparation, physical characterization, homogeneity estimation, chemical
      characterization, calculation of recommended reference values and associated
      uncertainties, methodology development and application, and performance of
      inorganic analytical methods in a multielement, multilaboratory, collaborative
      characterization campaign.

PMID- 11451253
TI  - Selenomethionine content of candidate reference materials.
AB  - Selenium has been identified as an antioxidant of importance in the diet.
      Accurate determination of its chemical forms depends on the availability of
      suitable reference materials (RMs). Two candidate reference materials for
      determination of selenomethionine (Semet) in food-related materials, a standard
      wheat gluten sample (NIST RM 8418 Wheat Gluten) and a commercial selenium
      enriched yeast, have been examined by use of a gas chromatography-isotope
      dilution mass spectrometry (IDMS) procedure, after treatment of the matrix with
      0.1 mol L(-1) hydrochloric acid containing stannous chloride, addition of CNBr,
      and extraction with chloroform. This procedure results in cleavage of the CH3Se
      group to form volatile CH3SeCN. Addition of isotopically enriched 74Semet to an
      analytical sample enables estimation of the naturally occurring protein-bound
      80Semet by IDMS without a protein-digestion process. We found that the Wheat
      Gluten RM contains a significant amount of Semet as a portion of its assigned
      value of 2.58 microg Se(total g(-1). Commercial selenium yeast tablets are
      labeled as containing an elevated level of "organic selenium", usually as Semet.
      The sample we investigated contained 210 microg Se(total) g(-1) sample as
      determined separately by IDMS, measuring elemental selenium after digestion. 73%
      of this total (153 +/- 21 microg Se(semet) g(-1); n = 23) was present as Semet.
      Thus, these two materials contain significant amounts of their total selenium
      content as Semet and would be good candidates for further study and
      characterization as reference materials for determining this important food
      component. The CNBr reaction used will also enable the determination of Se
      (methyl)selenocysteine, the biological role of which is of recent interest. In
      addition to matrix RMs for Semet, it is important to have standard materials of
      the pure substance. We have examined a sample of a candidate standard material of
      selenomethionine being prepared by the USP. It was confirmed that this material
      is pure selenomethionine.

PMID- 11451254
TI  - A natural matrix (pureed tomato) candidate reference material containing residue
      concentrations of pesticide chemicals.
AB  - NARL (the Australian National Analytical Reference Laboratory) is preparing a
      pureed tomato reference material spiked with residue concentrations of a range of
      pesticide chemicals relevant to the Australian horticultural industry. Traceable
      certified pesticide concentration values will be established using both isotope
      dilution mass spectrometry primary methods (developed within NARL) and
      measurements carried out by a number of experienced laboratories. As far as we
      are aware, there is no other similar CRM available anywhere in the world. The
      need for such a material is evident from the results of interlaboratory
      proficiency studies conducted by NARL among Australian and Asia-Pacific residue
      testing laboratories. Many participants are experiencing difficulties with the
      analysis of pesticide residues in fruit and vegetables at concentrations of
      regulatory significance. Chemicals such as methamidophos (an organophosphorus
      pesticide widely used on tomato crops) are causing particular problems. In a
      pilot study, a number of units of control (unspiked tomato) and the candidate
      reference material were prepared and packaged into lacquered steel cans which
      were sealed and sterilised by immersion in boiling water. Accelerated stability
      testing of the packaged material was conducted using isochronous measurement. All
      of the pesticides showed some degree of degradation after 4 weeks of storage at
      50 degrees C, and after 168 days of storage at room temperature. However, all
      appeared to be stable after 168 days of freezer storage. Homogeneity testing
      involved duplicate test portions taken from every 50th unit of reference
      material. An experimental protocol was devised with the aim of minimising the
      analytical variability and assuring the quality of the data generated. There is
      some degree of inhomogeneity in the prepared material and a small fill trend is
      also indicated. Potential improvements to the spiking and preparation procedure
      have been identified and it is planned to prepare a second batch of both control
      and spiked material for further homogeneity trials and for certification of the
      pesticide concentrations.

PMID- 11451255
TI  - Long-term stability of nutrients in a frozen mixed food control material.
AB  - A mixed food homogenate was prepared as a quality control material for two multi
      center clinical feeding trials. Approximately 100 kg of homogenized human diet
      material was prepared under controlled conditions to maintain the stability of
      lipid components. More than 4,800 20-25 g aliquots were prepared and stored at 
      60 degrees C in glass jars with Teflon-lined lids. The homogeneity of the
      composite was validated by analysis of moisture and total fat in aliquots taken
      throughout the dispensing sequence. A portion of the material was reserved at the
      National Institute of Standards and Technology and further characterized as SRM
      1544-Fatty Acids in Diet Composite. Moisture, protein, ash, total lipid, fatty
      acids, cholesterol, sodium, potassium, calcium, and magnesium were assayed as
      part of routine quality-control analyses. Components were analyzed over a total
      time period ranging from 29 months (minerals) to 60 months (moisture), and up to
      319 values per nutrient were generated. Results for all components assayed were
      stable over the time period studied. For example, moisture (n = 319; 60 months)
      ranged from 70.66 to 72.58 g/100 g with a mean, standard deviation (SD), and
      relative standard deviation (RSD) of 71.90, 0.27, and 0.4%, respectively. The
      range, mean, SD, and RSD for cholesterol (mg/100 g; n = 98; 49 months) were 13.54
      17.96, 15.14, 0.64, and 4%.

PMID- 11451256
TI  - Initiation of hormone replacement therapy after acute myocardial infarction is
      associated with more cardiac events during follow-up.
AB  - OBJECTIVES: This study explored the association between the initiation of hormone
      replacement therapy (HRT) and early cardiac events (<1 year) in women with a
      recent myocardial infarction (MI). BACKGROUND: Observational studies have linked
      postmenopausal hormone use with a reduced risk of death from heart disease.
      However, a recent randomized trial of HRT found no long-term benefit, primarily
      due to an increase in cardiac events in the first year. METHODS: The Coumadin
      Aspirin Reinfarction Study (CARS) database contains information on HRT use and
      menopausal status for women with a recent MI. We classified the 1,857
      postmenopausal women in CARS as prior/current HRT users if they took HRT before
      enrollment, new users if they began HRT during the study period or never users.
      We assessed the incidence of cardiac events (death, MI, unstable angina [UA])
      during follow-up. RESULTS: In our cohort, 28% (n = 524) used HRT at some point.
      Of these, 21% (n = 111) began HRT after their MI. New users had a higher
      incidence of death/MI/UA (41% vs. 28%, p = 0.001) during follow-up than never
      users, largely due to a higher incidence of UA (39% vs. 20%, p = 0.001). After
      adjustment, new users still had a significantly higher risk of death/MI/UA than
      never users during follow-up (relative risk [RR] = 1.44 [1.05-1.99]).
      Prior/current users had no excess risk of the composite end point after
      adjustment. Users of estrogen/progestin had a lower incidence of death/MI/UA
      during follow-up than users of estrogen only (RR = 0.56 [0.37-0.85]).
      CONCLUSIONS: Postmenopausal women who initiated HRT after a recent MI had an
      increased risk of cardiac events largely due to excess UA during follow-up.

PMID- 11451257
TI  - Screening patients with chest pain in the emergency department using electron
      beam tomography: a follow-up study.
AB  - OBJECTIVES: The high sensitivity of electron beam tomography (EBT) in the
      detection of coronary artery calcium (CAC) and obstructive coronary artery
      disease prompted us to investigate the association between CAC detection and
      future cardiac events in patients with acute chest pain syndromes requiring
      hospitalization. BACKGROUND: Three studies have documented that EBT is a rapid
      and efficient screening tool for patients admitted to the emergency department
      (ED) with chest pain, but there is a paucity of long-term follow-up data on these
      chest pain patients. METHODS: We conducted a prospective observational study of
      192 patients admitted to the ED of a large tertiary care hospital for chest pain
      syndromes. Upon admission, patients underwent EBT scanning in addition to the
      usual care for chest pain syndromes. During the 17-month enrollment period, 221
      patients were scanned (54% men with a mean age of 53 +/- 9 years). Average follow
      up was 50 +/- 10 months using chart review. RESULTS: Fifty-eight patients had
      coronary events confirmed by a blinded medical record review. The presence of CAC
      (a total calcium score >0) and increasing score quartiles were strongly related
      to the occurrence of hard cardiac events including myocardial infarction and
      death (p < 0.001) and all cardiovascular events (p < 0.001). Stratification by
      age- and gender-matching further increased the prognostic ability of EBT (for
      scores above vs. below the age- and gender-matched CAC scores; odds ratio: 13.1,
      95% confidence intervals: 5.62, 35.9). CONCLUSIONS: These data support previous
      reports demonstrating that the presence of CAC in a symptomatic cohort is a
      strong predictor of future cardiac events. This study supports the use of EBT in
      a symptomatic cohort with prompt discharge of those patients with negative scans.
      Furthermore, the absence of CAC is associated with a very low risk of future
      cardiac risk events in this population over the subsequent seven years (annual
      event rate <1%).

PMID- 11451258
TI  - Transient left ventricular apical ballooning without coronary artery stenosis: a
      novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris
      Myocardial Infarction Investigations in Japan.
AB  - OBJECTIVES: To determine the clinical features of a novel heart syndrome with
      transient left ventricular (LV) apical ballooning, but without coronary artery
      stenosis, that mimics acute myocardial infarction, we performed a multicenter
      retrospective enrollment study. BACKGROUND: Only several case presentations have
      been reported with regard to this syndrome. METHODS: We analyzed 88 patients (12
      men and 76 women), aged 67 +/- 13 years, who fulfilled the following criteria: 1)
      transient LV apical ballooning, 2) no significant angiographic stenosis, and 3)
      no known cardiomyopathies. RESULTS: Thirt-eight (43%) patients had preceding
      aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy
      [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and
      noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%)
      patients had emotional and physical problems (sudden accident [n = 2],
      death/funeral of a family member [n = 7], inexperience with exercise [n = 6],
      quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n =
      4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q
      wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase
      (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock
      (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New
      York Heart Association function on discharge. The LV ejection fraction improved
      from 41 +/- 11% to 64 +/- 10%. Transient intraventricular pressure gradient and
      provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the
      patients, respectively. During follow-up for 13 +/- 14 months, two patients
      showed recurrence, and one died suddenly. CONCLUSIONS: A novel cardiomyopathy
      with transient apical ballooning was reported. Emotional or physical stress might
      play a key role in this cardiomyopathy, but the precise etiologic basis still
      remains unclear.

PMID- 11451259
TI  - Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial
      dysfunction and increased plasma concentrations of asymmetric dimethylarginine.
AB  - OBJECTIVES: The aim of this study was to investigate endothelial function and
      common carotid intima-media thickness (IMT) in healthy young men with mild-to
      moderate hypertriglyceridemia. Plasma asymmetric dimethylarginine (ADMA), an
      endogenous nitric oxide synthase inhibitor, was measured to further elucidate the
      mechanisms involved. BACKGROUND: Hypertriglyceridemia is a risk factor for
      coronary heart disease although the mechanisms behind the increased risk remain
      to be defined. Acute elevation of plasma triglycerides induced by an intravenous
      fat load is associated with impaired endothelial function. The results of studies
      examining acute effects induced by a high-fat meal or effects of chronic
      hypertriglyceridemia on endothelial function are more inconsistent. METHODS: Flow
      mediated vasodilation and nitroglycerin-induced vasodilation of the brachial
      artery and common carotid IMT were measured noninvasively by ultrasound technique
      in 15 hypertriglyceridemic (HTG) subjects and 15 matched controls, mean age 34
      years. Plasma concentrations of ADMA were measured by high-performance liquid
      chromatography. RESULTS: Flow-mediated vasodilation was decreased in the HTG
      group (p < 0.0001), whereas nitroglycerin-induced vasodilation and carotid IMT
      did not differ significantly. Asymmetric dimethylarginine concentrations were
      higher in the HTG group (p < 0.05). CONCLUSIONS: Hypertriglyceridemia in young
      men is associated with endothelial dysfunction and increased plasma concentration
      of ADMA but not with increased IMT of the common carotid artery. The corollary is
      that chronic hypertriglyceridemia results in endothelial dysfunction, possibly
      due to increased ADMA concentration, and that endothelial dysfunction might
      precede increased IMT among the early manifestations of atherosclerosis.

PMID- 11451260
TI  - Assessment of coronary flow velocity with transthoracic Doppler echocardiography
      during dobutamine stress echocardiography.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility of
      measuring coronary flow velocity (CFV) by transthoracic Doppler echocardiography
      (TTDE) in the left anterior descending coronary artery (LAD) during contrast
      enhanced dobutamine stress echocardiography (DSE). We also assessed the value of
      TTDE for detecting stress-induced myocardial ischemia in the LAD territory.
      BACKGROUND: Noninvasive assessment of both CFV and wall motion during DSE would
      enhance the diagnostic accuracy of DSE. METHODS: One hundred forty-four
      consecutive patients underwent CFV recording in the distal LAD by TTDE during
      contrast-enhanced DSE. Regional wall motion score index (WMSI) in the LAD
      territory and CFV ratio at peak stress (CFV ratio peak), defined as a ratio of
      CFV at peak stress to basal CFV, were obtained. RESULTS: Coronary flow velocity
      was successfully recorded in 129 patients (90%) at baseline and during dobutamine
      infusion. Mean value of CFV ratio peak was 2.39 +/- 0.83 (range: 0.84 to 4.40).
      There was good correlation between WMSI at peak stress and CFV ratio peak (r =
      0.62, p < 0.001). Coronary flow velocity ratio peak was significantly lower in
      patients who developed stress-induced wall motion abnormality (WMA) in the LAD
      territory than it was in those patients without WMA (1.51 +/- 0.51 vs. 2.76 +/-
      0.65, p < 0.001). A CFV ratio peak <2.1 had a sensitivity of 92% and a
      specificity of 86% for detecting the presence of stress-induced WMA. CONCLUSIONS:
      Assessment of CFV in the distal LAD during DSE is feasible in the majority of
      cases and provides a CFV ratio for detecting stress-induced myocardial ischemia
      in the LAD territory.

PMID- 11451261
TI  - The impact of anti-endotoxin core antibodies on endotoxin and cytokine release
      and ventilation time after cardiac surgery.
AB  - OBJECTIVES: We hypothesized that a temporary cardiopulmonary bypass (CPB)-induced
      reduction of endotoxin antibody levels contributes to elevated endotoxin levels
      and the associated inflammatory consequences, with a significant influence on the
      postoperative ventilation time period. BACKGROUND: Cardiac surgery using CPB
      induces a systemic inflammatory response syndrome with an associated risk of
      increased postoperative morbidity and mortality. METHODS: A total of 100
      consecutive patients undergoing elective coronary artery bypass graft surgery
      using CPB were prospectively investigated. Endotoxin core antibodies
      (immunoglobulin [Ig] M/IgG against lipid A and lipopolysaccharide), endotoxin,
      interleukin (IL)-1-beta, IL-6, IL-8 and tumor necrosis factor-alpha were measured
      serially from 24 h preoperatively until 72 h postoperatively. RESULTS: Eighty
      five patients had no complications (group 1), whereas 15 patients required
      prolonged ventilation (group 2). In both groups, there was a decrease of all
      antibodies 5 min after CPB onset, compared with baseline values (p < 0.001), an
      increase of endotoxin and IL-8 peaking at 30 min postoperatively (p < 0.001) and
      an increase of IL-6 peaking 3 h postoperatively (p < 0.001). In group 2,
      preoperative antibody levels were lower (p < 0.01)--specifically, the decrease in
      IgM was significantly stronger and of longer duration (p < 0.002)--and levels of
      endotoxin (p < 0.001) and IL-8 (p < 0.001) were higher at 30 min postoperatively.
      CONCLUSIONS: We conclude that an CPB-associated temporary reduction of anti
      endotoxin core antibody levels contributes to elevated endotoxin and IL-8
      release. Furthermore, lower levels of IgM anti-endotoxin core antibodies were
      associated with a greater rise in endotoxin and IL-8, as well as prolonged
      respirator dependence.

PMID- 11451262
TI  - Postoperative stroke in cardiac surgery is related to the location and extent of
      atherosclerotic disease in the ascending aorta.
AB  - OBJECTIVES: The aim of the study was to evaluate the risk from calcified
      atheromas in the ascending aorta, and the extent and topography of the disease in
      the development of stroke after cardiac surgery. BACKGROUND: Postoperative stroke
      constitutes a serious problem in cardiac surgery, and atherosclerosis of the
      ascending aorta is an important risk factor. METHODS: Before surgical
      manipulation epiaortic echocardiographic ultrasound was performed to evaluate the
      ascending aorta in 921 consecutive patients undergoing cardiac surgery. The
      presence of calcification, location of atheroma, extent of the disease and
      clinical variables including postoperative stroke were recorded prospectively.
      RESULTS: A total of 26.2% of the patients had atherosclerosis of the ascending
      aorta, and in 44.4% of them more than one of 12 possible segments was involved.
      Logistic regression showed that atherosclerotic disease in the ascending aorta
      was the most important predictive factor for postoperative stroke. The incidence
      of stroke was 1.8% in patients without atherosclerotic disease of the ascending
      aorta, and 8.7% in patients with the disease (p < 0.0001). Diabetes mellitus was
      also a predictive factor (p = 0.04). A new and unique finding of this study was
      that the middle-lateral segment is an independent predictive factor for
      postoperative stroke, with a relative risk of 26% (p = 0.04). CONCLUSIONS:
      Patients with atheromatosis in the ascending aorta had an 8.7% incidence of
      postoperative stroke, in spite of minor surgical modifications. The risk depended
      on the presence, location and extent of the disease. Randomized trials evaluating
      alternative surgical strategies in coronary surgery are urgently needed in high
      risk patients.

PMID- 11451263
TI  - Risk stratification after successful coronary revascularization: the lack of a
      role for routine exercise testing.
AB  - OBJECTIVE: The objective of this study was to evaluate the American College of
      Cardiology/American Heart Association (ACC/AHA) guidelines for exercise testing
      (EXT) after successful coronary revascularization (CR) using the Bypass
      Angioplasty Revascularization Investigation experience. BACKGROUND: The ACC/AHA
      guidelines state that EXT within three years of successful CR is not useful.
      METHODS: The 1,678 patients randomized to CR by either angioplasty or bypass
      surgery were required to take symptom-limited treadmill tests one, three and five
      years after revascularization. RESULTS: Patients who took the test at each
      specified time had a much lower subsequent two-year mortality than those who did
      not (1.9% vs. 9.4%, 3.5% vs. 12.6% and 3.3% vs. 11.0% at one, three and five
      years, respectively, after CR [p < 0.0001 for each]). Exercise parameters at the
      one- and three-year test did not improve a multivariable model of survival after
      including clinical parameters. Exercising to Bruce stage 3 or generating a Duke
      score >-6 were independently predictive of two-year survival after the five-year
      test. ST depression on the one-year test was associated with more
      revascularizations (relative risk = 1.6; p < 0.001). CONCLUSIONS: Patients with
      stable multivessel coronary disease who took a protocol-mandated exercise test at
      one, three and five years after revascularization were at low risk for mortality
      in the two years subsequent to each test. Exercise parameters did not improve
      prediction of mortality in the two years after the one- and three-year tests. The
      ACC/AHA guidelines on exercise testing after CR (no value for routine testing in
      stable patients for three years after revascularization) are supported by these
      results.

PMID- 11451264
TI  - Percutaneous coronary intervention versus coronary artery bypass graft surgery
      for patients with medically refractory myocardial ischemia and risk factors for
      adverse outcomes with bypass: a multicenter, randomized trial. Investigators of
      the Department of Veterans Affairs Cooperative Study #385, the Angina With
      Extremely Serious Operative Mortality Evaluation (AWESOME).
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass
      graft surgery (CABG) are being applied to high-risk populations, but previous
      randomized trials comparing revascularization methods have excluded a number of
      important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized
      clinical trial was designed to compare long-term survival among patients with
      medically refractory myocardial ischemia and a high risk of adverse outcomes
      assigned to either a CABG or a PCI strategy, which could include stents. METHODS:
      Patients from 16 Veterans Affairs Medical Centers were screened to identify
      myocardial ischemia refractory to medical management and the presence of one or
      more risk factors for adverse outcome with CABG, including prior open-heart
      surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial
      infarction within seven days or intraaortic balloon pump required. Clinically
      eligible patients (n = 2,431) underwent coronary angiography; 781 were
      angiographically acceptable; 454 (58% of eligible) patients consented to random
      assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized
      to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%,
      respectively. Survival rates for CABG and PCI were 90% versus 94% at six months
      and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS:
      Percutaneous coronary intervention is an alternative to CABG for patients with
      medically refractory myocardial ischemia and a high risk of adverse outcomes with
      CABG.

PMID- 11451265
TI  - Are we making progress with percutaneous saphenous vein graft treatment? A
      comparison of 1990 to 1994 and 1995 to 1998 results.
AB  - OBJECTIVES: We sought to determine whether strategies to reduce procedural distal
      embolization and late repeat revascularization have resulted in more favorable
      outcomes after saphenous vein graft (SVG) angioplasty. BACKGROUND: Angioplasty of
      SVG lesions has been associated with frequent procedural and late cardiac events.
      Therefore, evolving strategies have been attempted to improve outcomes after SVG
      angioplasty. METHODS: We compared our earlier experience (1990 to 1994) of 1,055
      patients with 1,412 SVG lesions with a recent group (1995 to 1998) of 964
      patients with 1,315 lesions. RESULTS: Baseline characteristics were similar
      between the groups. However, there were significantly more unfavorable lesion
      characteristics (older, longer and significantly more degenerated SVGs) in the
      recent series. Between the two periods, there was decreased use ofatheroablative
      devices, whereas stent use increased. The procedural success rates (96.6% vs.
      96.1%) were similar. However, one-year outcome (event-free survival) was
      significantly improved in the more recent experience (70.7% vs. 59.1%, p <
      0.0001), especially late mortality (6.1% vs. 11.3%, p < 0.0001). Multivariate
      analysis showed stent use to be the only protective variable for both periods.
      CONCLUSIONS: This study shows that despite higher risk lesions, strategies to
      reduce distal embolization have maintained high procedural success. Late cardiac
      events, including mortality, have also been substantially reduced.

PMID- 11451266
TI  - Assessment of flow velocity reserve by transthoracic Doppler echocardiography and
      venous adenosine infusion before and after left anterior descending coronary
      artery stenting.
AB  - OBJECTIVES: We sought to evaluate whether coronary flow velocity reserve (CFR)
      (the ratio between hyperemic and baseline peak flow velocity), as measured by
      transthoracic Doppler echocardiography during adenosine infusion, allows
      detection of flow changes in the left anterior descending coronary artery (LAD)
      before and after stenting. BACKGROUND: The immediate post-stenting evaluation of
      CFR by intracoronary Doppler has shown mixed results, due to reactive hyperemia
      and microvascular stunning. Noninvasive coronary Doppler echocardiography may be
      a more reliable measure than intracoronary Doppler. METHODS: Transthoracic
      Doppler echocardiography during 90-s venous adenosine infusion (140 microg/kg
      body weight per min) was used to measure CFR of the LAD in 45 patients before and
      3.7 +/- 2 days after successful stenting, as well as in 25 subjects with an
      angiographically normal LAD (control group). RESULTS: Adequate Doppler spectra
      were obtained in 96% of the patients. Pre-stent CFR was significantly lower in
      patients than in control subjects (diastolic CFR: 1.45 +/- 0.5 vs. 2.72 +/- 0.71,
      p < 0.01; systolic CFR: 1.61 +/- 1.02 vs. 2.41 +/- 0.68, p < 0.01) and increased
      toward the normal range after stenting (diastolic CFR: 2.58 +/- 0.7 vs. 2.72 +/-
      0.75, p = NS; systolic CFR: 2.43 +/- 1.01 vs. 2.41 +/- 0.52, p = NS). Diastolic
      CFR was often damped, suggesting coronary steal in patients with > or =90% versus
      <90% LAD stenosis (0.86 +/- 0.23 vs. 1.69 +/- 0.43, p < 0.01). Coronary stenting
      normalized diastolic CFR in these two groups (2.45 +/- 0.77 and 2.64 +/- 0.69,
      respectively, p = NS), even though impaired diastolic CFR persisted in three of
      four patients with > or =90% stenosis. Stenosis of the LAD was better
      discriminated by diastolic (F = 49.30) than systolic (F = 12.20) CFR (both p <
      0.01). CONCLUSIONS: Coronary flow reserve, as measured by transthoracic Doppler
      echocardiography, is impaired in LAD disease; it may identify patients with > or
      =90% stenosis; and it normalizes early after stenting, even in patients with > or
      =90% stenosis.

PMID- 11451267
TI  - Outcome of mild periprosthetic regurgitation detected by intraoperative
      transesophageal echocardiography.
AB  - OBJECTIVES: The goal of this study was to determine the outcome of trivial or
      mild periprosthetic regurgitation (PPR) identified by intraoperative
      transesophageal echocardiography (TEE). BACKGROUND: The clinical significance,
      natural history and correlates of trivial or mild PPR detected early after
      surgery are unknown. METHODS: Between 1992 and 1997, 608 consecutive patients
      underwent isolated aortic valve replacement or mitral valve replacement at
      Dartmouth-Hitchcock Medical Center. Of these, 113 patients (18.3%) were found to
      have trivial or mild PPR at surgery by TEE. Follow-up transthoracic
      echocardiograms (early TTEs) were obtained within six weeks of surgery in 99.0%
      of patients and late TTEs (mean 2.1 years) in 54.3%. Clinical, intraoperative and
      outcome variables associated with PPR were identified using t test, chi-square
      and logistic regression analyses. RESULTS: By univariate analysis, compared with
      patients without PPR, patients with PPR were older, of smaller body surface area
      (BSA), had degenerative valve disease more often and were more likely to receive
      a bioprosthetic valve. By multivariate analysis, smaller BSA and the use of a
      bioprosthesis were the strongest predictors of PPR (p < 0.01). At early TTE, PPR
      was not observed (n = 56) or remained unchanged (n = 44) in all patients. At late
      TTE, four patients were found to have progression of their PPR. All four patients
      had bioprosthetic valves. Two of these patients had endocarditis, and one had
      primary valvular degeneration. The fourth patient had progressive PPR.
      CONCLUSIONS: Trivial or mild PPR is a frequent finding on intraoperative TEE.
      Smaller body size and the use of a bioprosthetic valve are significantly
      associated with PPR. The clinical significance and natural history of PPR is
      benign in most cases.

PMID- 11451268
TI  - Progression to chronic atrial fibrillation after pacing: the Canadian Trial of
      Physiologic Pacing. CTOPP Investigators.
AB  - OBJECTIVES: This study examined the effect of physiologic pacing on the
      development of chronic atrial fibrillation (CAF) in the Canadian Trial Of
      Physiologic Pacing (CTOPP). BACKGROUND: The role of physiologic pacing to prevent
      CAF remains unclear. Small randomized studies have suggested a benefit for
      patients with sick sinus syndrome. No data from a large randomized trial are
      available. METHODS: The CTOPP randomized patients undergoing first pacemaker
      implant to ventricular-based or physiologic pacing (AAI or DDD). Patients who
      were prospectively found to have persistent atrial fibrillation (AF) lasting
      greater than or equal to one week were defined as having CAF. Kaplan-Meier plots
      for the development of CAF were compared by log-rank test. The effect of baseline
      variables on the benefit of physiologic pacing was evaluated by Cox proportional
      hazards modeling. RESULTS: Physiologic pacing reduced the development of CAF by
      27.1%, from 3.84% per year to 2.8% per year (p = 0.016). Three clinical factors
      predicted the development of CAF: age > or =74 years (p = 0.057), sinoatrial (SA)
      node disease (p < 0.001) and prior AF (p < 0.001). Subgroup analysis demonstrated
      a trend for patients with no history of myocardial infarction or coronary disease
      (p = 0.09) as well as apparently normal left ventricular function (p = 0.11) to
      derive greatest benefit. CONCLUSIONS: Physiologic pacing reduces the annual rate
      of development of chronic AF in patients undergoing first pacemaker implant. Age
      > or =74 years, SA node disease and prior AF predicted the development of CAF.
      Patients with structurally normal hearts appear to derive greatest benefits.

PMID- 11451269
TI  - The adenosine triphosphate test: a bedside diagnostic tool for identifying the
      mechanism of supraventricular tachycardia in patients with palpitations.
AB  - OBJECTIVES: This study assesses the value of the "ATP test" (injection of
      adenosine triphosphate [ATP] during sinus rhythm) for identifying patients with
      palpitations of unclear etiology who actually have atrioventricular (AV) nodal re
      entry tachycardia (AVNRT) or AV re-entry tachycardia (AVRT). BACKGROUND: Because
      AVNRT and AVRT can be cured with radiofrequency ablation, documentation of
      spontaneous AVNRT or AVRT usually prompts referral for electrophysiologic (EP)
      evaluation. However, these paroxysmal arrhythmias may elude clinical diagnosis.
      We recently showed that administration of ATP during sinus rhythm often reveals
      dual AV node physiology or a concealed accessory pathway (AP) in patients with
      documented AVNRT or AVRT. Thus, we postulated that the ATP test could identify
      patients with palpitations who actually have AVNRT or AVRT and would therefore
      benefit from EP evaluation. METHODS: One hundred forty-six patients (54 with
      "palpitations without documented arrhythmias" and 92 with "documentation of
      arrhythmias of unclear mechanism") underwent a noninvasive ATP test. ATP was
      injected during sinus rhythm using 10 mg increments. The ATP test was considered
      positive when prospectively defined signs of dual AV node physiology or concealed
      AP were disclosed in the electrocardiogram. These findings were correlated with
      the results of EP evaluation. RESULTS: A positive ATP test predicted induction of
      AVNRT or AVRT with a positive predictive value of 93% (sensitivity 71%) but a
      negative predictive value of 37% (specificity 76%). CONCLUSIONS: A bedside ATP
      test identifies patients with palpitations who are likely to have AVNRT or AVRT
      (and who are therefore likely to benefit from EP evaluation) with a high positive
      predictive value.

PMID- 11451270
TI  - Decreased oxidative stress in patients with idiopathic dilated cardiomyopathy one
      year after immunoglobulin adsorption.
AB  - OBJECTIVES: In a substudy to a recently reported investigation that demonstrated
      the benefit of immunoglobulin adsorption (immunoadsorption) for patients with
      idiopathic dilated cardiomyopathy (IDC), we tested whether this benefit is
      associated with a reduction of oxidative stress. BACKGROUND: The progression of
      cardiomyopathy is believed to be related to the increase of oxidative stress.
      Therefore, reduction of oxidative stress could be one of the effects of
      immunoadsorption for improvement of cardiac performance and clinical status.
      METHODS: Plasma markers for oxidative stress-thiobarbituric acid-reactive
      substances (TBARS), lipid peroxides (LPO), anti-oxidized low-density lipoprotein
      autoantibodies (anti-oxLDL-AB), thiol groups and vitamin E-were compared in 31
      patients, of whom 16 underwent immunoadsorption and 15 received conventional
      treatment (controls). All patients received a daily supplement of vitamins,
      minerals and trace elements. RESULTS: After one year, TBARS (p = 0.026), LPO (p =
      0.026) and anti-oxLD

PMID- 11451271
TI  - Autoimmunity, immunoglobulin adsorption and dilated cardiomyopathy: has the time
      come for randomized clinical trials?

PMID- 11451272
TI  - Enhanced gene expression of chemokines and their corresponding receptors in
      mononuclear blood cells in chronic heart failure--modulatory effect of
      intravenous immunoglobulin.
AB  - OBJECTIVES: We sought to study the gene expression of chemokines and their
      corresponding receptors in mononuclear blood cells (MNCs) from patients with
      chronic heart failure (CHF), both of which were cross-sectional and longitudinal
      studies during therapy with intravenous immunoglobulin (IVIg). BACKGROUND: We
      have recently demonstrated that IVIg improves left ventricular ejection fraction
      (LVEF) in patients with CHF. Based on the potential pathogenic role of chemokines
      in CHF, we hypothesized that the beneficial effect of IVIg may be related to a
      modulatory, effect on the expression of chemokines and their receptors in MNCs.
      METHODS: We examined: 1) the gene expression of C, CC and CXC chemokines and
      their receptors in MNCs from 20 patients with CHF and 10 healthy blood donors;
      and 2) the expression of these genes in MNCs from 20 patients with CHF randomized
      in a double-blind fashion to therapy with IVIg or placebo for 26 weeks. RESULTS:
      Our main findings in CHF were: 1) markedly raised gene expression of macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta and interleukin (IL)-8; 2) enhanced
      gene expression of their corresponding receptors; 3) modulation in a normal
      direction of this abnormal chemokine and chemokine receptor gene expression
      during IVIg, but not during placebo therapy; 4) down-regulation of MIP-1alpha,
      MIP-1beta and IL-8 during IVIg at the protein level in plasma; and 5) a
      correlation between down-regulation of MIP-1alpha gene expression and improved
      LVEF during IVIg therapy. CONCLUSIONS: Our results further support a pathogenic
      role for chemokines in CHF and suggest that IVIg may represent a novel
      therapeutic approach, with the potential to improve LVEF in patients with CHF,
      possibly by modulatory effects on the chemokine network.

PMID- 11451273
TI  - Intravenous myocardial contrast echocardiography predicts recovery of dysynergic
      myocardium early after acute myocardial infarction.
AB  - OBJECTIVES: We aimed to ascertain whether triggered intravenous myocardial
      contrast echocardiography (MCE) can predict functional recovery in patients with
      acute myocardial infarction (AMI) and to determine the optimal triggering
      interval in this setting. BACKGROUND: Detection of myocardial viability early
      after AMI has both therapeutic and prognostic implications. Myocardial contrast
      echocardiography using intracoronary injections of contrast can detect viable
      myocardium, but there is little data on the use of recently developed intravenous
      MCE techniques for this purpose. METHODS: Ninety-six patients with recent AMI
      (4.8 +/- 1.7 days) underwent echocardiography at baseline and six months later or
      three months after revascularization to determine regional function (score 1 =
      normal to 3 = akinetic). Myocardial contrast echocardiography was performed at
      baseline using intravenous injections of Optison. Triggering intervals of 1:1
      (early) and 1:10 (delayed) cardiac cycles were used. Segments were deemed viable
      if they demonstrated homogeneous contrast opacification. RESULTS: Of 400 akinetic
      segments at baseline, 109 (27%) improved during the follow-up period, and 375
      (94%) were adequately visualized with MCE, of which 59 (16%) were homogeneously
      opacified by early and 125 (33%) by delayed MCE (negative predictive value for
      recovery of contractile function 74% and 84%, positive predictive value 29% and
      47%, respectively). Independent predictors of functional recovery were delayed
      MCE (odds ratio [OR]: 4.0, p < 0.001), revascularization (OR: 6.0, p < 0.001),
      and log creatine kinase (OR: 0.5, p = 0.03). However, the presence or absence of
      >90% stenosis of the infarct-related artery did not influence the ability of
      triggered MCE to predict functional recovery. CONCLUSIONS: Intravenous delayed
      triggered MCE can independently detect myocardial viability early after AMI.

PMID- 11451274
TI  - Physical training in patients with chronic heart failure enhances the expression
      of genes encoding antioxidative enzymes.
AB  - OBJECTIVES: We sought to determine whether the benefit of training for
      vasodilation in the skeletal muscle vasculature of patients with chronic heart
      failure (CHF) is likely to be caused at the molecular level primarily by
      increased nitric oxide (NO) production or decreased inactivation of NO.
      BACKGROUND: Physical training reverses endothelium dysfunction in patients with
      CHF, mediated by increased NO bioactivity. Some animal studies support a
      mechanism whereby training results in increased vascular NO levels by sustained
      transcriptional activation of the endothelial NO synthase (eNOS) gene, presumably
      due to shear stress. The mechanism has not been addressed in patients with CHF.
      METHODS: The steady state transcript levels for eNOS and two other shear stress
      regulated genes (angiotensin-converting enzyme [ACE] and prostacyclin synthase
      [PGI2S]) were measured in samples of skeletal muscle from patients with CHF
      before and after 12 weeks of training. Transcript levels were measured in the
      same samples for two genes encoding antioxidant enzymes, copper zinc superoxide
      dismutase (Cu/Zn SOD) and glutathione peroxidase (GSH-Px). Untrained patients
      served as controls. RESULTS: As expected, training significantly enhanced peak
      oxygen uptake in the patients with CHF. Training did not increase steady-state
      transcript levels for eNOS, ACE or PGI2S. In striking contrast, training
      increased the expression of the antioxidative enzyme genes by approximately 100%.
      CONCLUSIONS: Our results do not support a model of benefit from training by
      increased eNOS expression. However, the data are entirely consistent with the
      alternative hypothesis, that reduced oxidative stress may account for the
      increase in vascular NO-mediated vasodilation. Insight into the mechanism may be
      relevant when considering therapies for exercise-intolerant patients with CHF.

PMID- 11451275
TI  - Depressive symptoms and risk of functional decline and death in patients with
      heart failure.
AB  - OBJECTIVES: We sought to examine whether depressive symptoms are associated with
      poorer prognosis in patients with heart failure. BACKGROUND: Depression is an
      established risk factor for poor outcome in patients with coronary heart disease
      (CHD). Little is known of its role in patients with heart failure. METHODS: We
      prospectively followed 391 patients > or =50 years of age who met criteria for
      decompensated heart failure on hospital admission. The outcome of the study was
      death or decline in activities of daily living (ADL) at six months, relative to
      baseline. Depressive symptoms were measured at baseline by means of the Geriatric
      Depression Scale, Short-Form, with 6 to 7 symptoms, 8 to 10 symptoms and > or =11
      symptoms indicating mild, moderate and severe levels of depressive symptoms,
      respectively. RESULTS: There was a strong and graded association between the
      severity of depressive symptoms at baseline and the rate of the combined end
      point of either functional decline or death at six months. After adjustment for
      demographic factors, medical history, baseline functional status and clinical
      severity, patients with > or =11 depressive symptoms, compared with those with <6
      depressive symptoms, had an 82% higher risk of either functional decline or
      death, whereas the intermediate levels of depressive symptoms showed intermediate
      risk (p = 0.003 for trend). A similar graded association was found for functional
      decline and death separately; however, after multivariate analysis, the
      association with mortality was less strong and no longer statistically
      significant. CONCLUSIONS: An increasing number of depressive symptoms is a
      negative prognostic factor for patients with heart failure, just as it is for
      patients with CHD.

PMID- 11451276
TI  - Impact of lipid abnormalities in development and progression of transplant
      coronary disease: a serial intravascular ultrasound study.
AB  - OBJECTIVES: We sought to determine the role of conventional atherosclerosis risk
      factors in the development and progression of transplant coronary artery disease
      (CAD) using serial intravascular ultrasound imaging. BACKGROUND: Transplant
      artery disease is a combination of allograft vasculopathy and donor
      atherosclerosis. The clinical determinants for each of these disease processes
      are not well characterized. Intravascular ultrasound imaging is the most
      sensitive tool to serially study these processes. METHODS: Baseline intravascular
      ultrasound imaging was performed 0.9 +/- 0.5 months after transplantation to
      identify donor atherosclerosis. Follow-up imaging was performed at 1.0 +/- 0.07
      year to evaluate progression of donor atherosclerosis and development of
      transplant vasculopathy. Conventional risk factors for CAD included recipient
      age, gender, smoking history, diabetes mellitus, hypertension and
      hypercholesterolemia. RESULTS: Donor-transmitted atherosclerosis was present in
      36 patients (39%). At follow-up, progression of donor lesions was seen in 15
      patients (42%) and 42 patients (45%) developed transplant vasculopathy, leaving
      35 patients (38%) without any disease. There was no difference in any
      conventional risk factors in patients with and without allograft vasculopathy.
      However, the severity of allograft vasculopathy was associated with a larger
      increase in low density lipoprotein (LDL) cholesterol from baseline (p = 0.02).
      High one-year posttransplant serum triglyceride level and pretransplant body mass
      index were the only significant predictors (p = 0.03) for progression of donor
      atherosclerosis. CONCLUSIONS: Conventional atherosclerosis risk factors do not
      predict development of allograft vasculopathy, but greater change in serum LDL
      cholesterol level during the first year after transplant is associated with more
      severe vasculopathy. Therefore, maintenance of LDL cholesterol as close to
      pretransplant values as possible may help to limit the rate of progression of
      acquired allograft vasculopathy.

PMID- 11451277
TI  - Pulmonary artery reflection for differentially diagnosing primary pulmonary
      hypertension and chronic pulmonary thromboembolism.
AB  - OBJECTIVES: The purpose of this investigation was to differentiate chronic
      pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by
      means of the indexes of pulmonary arterial reflection. BACKGROUND: These
      differences in the primary lesions would make pulmonary artery reflection occur
      earlier in CPTE than in PPH. Although the analysis of pulsatility of pulmonary
      arterial pressure is useful in the differential diagnosis of PPH and CPTE, it is
      not known whether the analysis of pulmonary artery reflection can differentiate
      CPTE from PPH. METHODS: Since CPTE predominantly involves the proximal arteries,
      whereas PPH involve the peripheral arteries, we hypothesized that patients with
      CPTE have a large augmentation index and a short inflection time. For this study,
      we enrolled 62 patients who had CPTE (31 patients) and PPH (31 patients). We
      measured pulmonary arterial pressure using a fluid filled system that included a
      balloon-tipped flow directed catheter. To quantify the pulmonary artery
      reflection, we used the augmentation index and inflection time. RESULTS: The
      augmentation index was markedly higher in CPTE than it was in PPH (27.4% +/-
      15.2% [SD] and -25.1% +/- 26.9%, respectively, p < 0.001) and was diagnostic in
      separating the two groups. Inflection time separated the two groups reasonably
      well (97 +/- 20 ms and 210 +/- 49 ms, respectively, p < 0.001). CONCLUSIONS: The
      analysis of pulmonary arterial reflection is useful in the differential diagnosis
      of CPTE and PPH.

PMID- 11451278
TI  - Changes in QRS voltage in cardiac tamponade and pericardial effusion:
      reversibility after pericardiocentesis and after anti-inflammatory drug
      treatment.
AB  - OBJECTIVES: The goal of this study was to define the association between low QRS
      voltage and cardiac tamponade or pericardial effusion and to assess the
      reversibility of low QRS voltage after therapeutic procedures. BACKGROUND: It is
      unclear whether low QRS voltage is a sign of cardiac tamponade or whether it is a
      sign of pericardial effusion per se. METHODS: In a prospective study design, we
      recorded consecutive 12-lead electrocardiograms and echocardiograms in 43
      patients who were referred to our institution for evaluation and therapy of a
      significant pericardial effusion. Cardiac tamponade was present in 23 patients
      (53%). Low QRS voltage (defined as maximum QRS amplitude <0.5 mV in the limb
      leads) was found in 14 of these 23 subjects (61%). Nine of these 14 patients were
      treated by pericardiocentesis (group A). Five patients received anti-inflammatory
      medication (group B). Group C consisted of nine patients with pericarditis and
      significant pericardial effusion who had no clinical evidence of tamponade.
      RESULTS: In group A, low QRS voltage remained largely unchanged immediately after
      successful pericardiocentesis (0.36 +/- 0.17 mV before vs. 0.42 +/- 0.21 mV
      after, p = NS), but QRS amplitude recovered within a week (0.78 +/- 0.33 mV, p <
      0.001). In group B, the maximum QRS amplitude increased from 0.40 +/- 0.20 mV to
      0.80 +/- 0.36 mV (p < 0.001) within six days. In group C, all patients had a
      normal QRS amplitude initially (1.09 +/- 0.55 mV) and during a seven-day follow
      up (1.10 +/- 0.56 mV, p = NS). CONCLUSIONS: Low QRS voltage is a feature of
      cardiac tamponade but not of pericardial effusion per se. Our findings indicate
      that the presence and severity of cardiac tamponade, in addition to inflammatory
      mechanisms, may contribute to the development of low QRS voltage in patients with
      large pericardial effusions.

PMID- 11451279
TI  - The pulse pressure-to-stroke index ratio predicts cardiovascular events and death
      in uncomplicated hypertension.
AB  - OBJECTIVES: The goal of this study was to assess the prognostic power of the
      pulse pressure-to-stroke index (PP-to-SVi) ratio for cardiovascular events and
      mortality in patients with uncomplicated hypertension. BACKGROUND: The prognostic
      significance of pulse pressure (PP) has been studied repeatedly, but few data are
      available on the PP-to-SVi ratio. METHODS: Invasive hemodynamic measurements,
      including brachial intra-arterial pressure and stroke index by the direct oxygen
      Fick method, were performed in the period 1972 to 1982 in 192 patients with
      uncomplicated hypertension; their outcome was ascertained in 1994. RESULTS: Age
      at baseline averaged 37 +/- 12 years; brachial artery pressure was 165 mm Hg +/-
      30/89 +/- 17 mm Hg; PP averaged 76 mm Hg +/- 18 mm Hg, and the PP-to-SVi ratio
      was 1.67 mm Hg/(ml/m2) +/- 0.73 mm Hg/(ml/m2). During 3,057 patient years of
      follow-up, 19 patients died, and 44 experienced at least one fatal or nonfatal
      cardiovascular event. Cox regression analysis revealed that the PP-to-SVi ratio
      was a significant predictor of fatal and nonfatal cardiovascular events and of
      all-cause mortality after control for age and gender (p < 0.01). Its predictive
      power persisted after additional adjustment for mean arterial pressure and heart
      rate. Each 0.75-mm Hg/(ml/m2) increase in the PP-to-SVi ratio was independently
      associated with a 79% increase in the risk of a cardiovascular event (p = 0.01)
      and a 2.05-fold greater risk of all-cause mortality (p = 0.01). CONCLUSIONS: The
      PP-to-SVi ratio is a significant and independent predictor of cardiovascular
      events and mortality in selected patients with uncomplicated hypertension.

PMID- 11451280
TI  - Effect of essential hypertension on cardiac autonomic function in type 2 diabetic
      patients.
AB  - OBJECTIVES: The aim of this study was to examine the effects of essential
      hypertension on cardiac autonomic function in type 2 diabetic patients.
      BACKGROUND: Hypertension is common in type 2 diabetic patients and is associated
      with a high mortality. However, the combined effects of type 2 diabetes and
      essential hypertension on cardiac autonomic function have not been fully
      elucidated. METHODS: Thirty-three patients with type 2 diabetes were assigned to
      a hypertensive diabetic group (n = 15; age: 56 +/- 8 years, mean +/- SD) or an
      age-matched normotensive diabetic group (n = 18, 56 +/- 6 years). Cardiac
      autonomic function was assessed by baroreflex sensitivity (BRS), heart rate
      variability (HRV), plasma norepinephrine concentration and cardiac 123I
      metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex
      sensitivity was lower in the hypertensive diabetic group than it was in the
      normotensive diabetic group (p < 0.05). The early and delayed myocardial uptake
      of 123I-MIBG was lower (p < 0.01 and p < 0.05, respectively), and the percent
      washout rate of 123I-MIBG was higher (p < 0.05) in the hypertensive diabetic
      group. However, the high frequency (HF) power and the ratio of low frequency (LF)
      power to HF power (LF/HF) of HRV and plasma norepinephrine concentration were not
      significantly different. The homeostasis model assessment index was higher in the
      hypertensive diabetic group than it was in the normotensive diabetic group (p <
      0.01). CONCLUSIONS: Our results indicate that essential hypertension acts
      synergistically with type 2 diabetes to depress cardiac reflex vagal and
      sympathetic function, and the results also suggest that insulin resistance may
      play a pathogenic role in these processes.

PMID- 11451281
TI  - Silent and clinically overt stroke in older Japanese subjects with white-coat and
      sustained hypertension.
AB  - OBJECTIVES: We investigated whether white-coat hypertension is a risk factor for
      stroke in relation to silent cerebral infarct (SCI) in an older Japanese
      population. BACKGROUND: It remains uncertain whether white-coat hypertension in
      older subjects is a benign condition or is associated with an increased risk of
      stroke. METHODS: We studied the prognosis for stroke in 958 older Japanese
      subjects (147 normotensives [NT], 236 white-coat hypertensives [WCHT] and 575
      sustained hypertensives [SHT]) in whom ambulatory blood pressure monitoring was
      performed in the absence of antihypertensive treatment. In 585 subjects (61%), we
      also assessed SCI using brain magnetic resonance imaging. RESULTS: Silent
      cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and
      53% of SHT (n = 361); multiple SCIs (the presence of > or =2 SCIs) were found in
      24% of NT, 25% of WCHT and 39% of SHT. During a mean 42-month follow-up period,
      clinically overt strokes occurred in 62 subjects (NT: three [2.0%]; WCHT: five
      [2.1%]; SHT: 54 [9.4%]), with 14 fatal cases (NT: one [0.7%]; WCHT: 0 [0%]; SHT:
      13 [2.3%]). A Cox regression analysis showed that age (p = 0.0001) and SHT
      (relative risk, [RR] [95% confidence interval, CI]: 4.3 [1.3-14.2], p = 0.018)
      were independent stroke predictors, whereas WCHT was not significant. When we
      added presence/absence of SCI at baseline into this model, the RR (95% CI) for
      SCI was 4.6 (2.0-10.5) (p = 0.003) and that of SHT was 5.5 (1.8-18.9) versus WCHT
      (p = 0.004) and 3.8 (0.88-16.7) versus NT (p = 0.07). CONCLUSIONS: In older
      subjects the incidence of stroke in WCHT is similar to that of NT and one-fourth
      the risk in SHT. Although SCI is a strong predictor of stroke, the difference in
      stroke prognosis between SHT and WCHT was independent of SCI. It is clinically
      important to distinguish WCHT from SHT even after assessment of target organ
      damage in the elderly.

PMID- 11451282
TI  - Lower standing systolic blood pressure as a predictor of falls in the elderly: a
      community-based prospective study.
AB  - OBJECTIVES: We investigated prospectively the relationships among falls, physical
      balance, and standing and supine blood pressure (BP) in elderly persons.
      BACKGROUND: Falls occur often and adversely affect the activities of daily living
      in the elderly; however, their relationship to BP has not been clarified
      thoroughly. METHODS: A total of 266 community-dwelling elderly persons age 65
      years or over (123 men and 143 women, mean age of 76 years) were selected from
      among residents of Coop City, Bronx, New York. Balance was evaluated at baseline
      using computerized dynamic posturography (DPG). During a one-year follow-up, we
      collected information on subsequent falls on a monthly basis by postcard and
      telephone follow-up. RESULTS: One or more falls occurred in 60 subjects (22%)
      during the one-year follow-up. Women fell more frequently than men (28% vs. 16%,
      p < 0.03), and fallers were younger than nonfallers. Fallers (n = 60) had lower
      systolic BP (SBP) levels when compared with nonfallers (n = 206) (128 +/- 17 vs.
      137 +/- 22 mm Hg for standing, p < 0.006; 137 +/- 16 vs. 144 +/- 22 mm Hg for
      lying, p < 0.02), whereas diastolic BP was not related to falls. Falls occurred
      2.8 times more often in the lower BP subgroup (<140 mm Hg for standing SBP) than
      in the higher BP subgroup (> or =140 mm Hg, p < 0.0003), and gender-related
      differences were observed (p = 0.006): 3.4 times for women (p < 0.0001) versus
      1.9 times for men (p = 0.30). Loss of balance, as detected by DPG, did not
      predict future falls and was also not associated with baseline BP levels.
      Multiple logistic regression analysis demonstrated that female gender (relative
      risk [RR] = 2.1, p = 0.02), history of falls (RR = 2.5, p = 0.008) and lower
      standing SBP level (RR = 0.78 for 10 mm Hg increase, p = 0.005) were independent
      predictors of falls during one year of follow-up. CONCLUSIONS: Lower standing
      SBP, even within normotensive ranges, was an independent predictor of falls in
      the community-dwelling elderly. Elderly women with a history of falls and with
      lower SBP levels should have more attention paid to the prevention of falls and
      related accidents.

PMID- 11451283
TI  - Echocardiographic assessment of obstructive lesions in atrioventricular septal
      defects.
AB  - OBJECTIVES: We sought to determine the accuracy of transthoracic echocardiography
      (TTE) in identifying risk factors in patients with an atrioventricular septal
      defect (AVSD). BACKGROUND: Atrioventricular septal defect is a common lesion, and
      many decisions about it are based on echocardiography alone. The identification
      of associated left-sided inflow and outflow obstructive lesions is important, as
      they are responsible for mortality and morbidity. METHODS: Between 1983 to 1998,
      549 patients with AVSD underwent repair. The TTE findings were correlated with
      surgery, angiocardiography, autopsy or postoperative TTE. Papillary muscle
      measurements were made in those with either a left ventricular outflow tract
      (LVOT) or left ventricular inflow abnormality and compared with those
      measurements from control subjects. Measurements of the LVOT were made in
      patients with an identified LVOT abnormality. RESULTS: There were 63 missed
      lesions, decreasing over time. Double-orifice left atrioventricular valve
      (DOLAVV) and nonobstructive chordae in the LVOT were more often missed.
      Reoperation was performed to address a missed lesion in 2 of 68 patients. Two of
      55 patients died of reasons related to a missed lesion. In 67% of patients,
      DOLAVV was missed. Abnormal papillary muscle angles were seen with either a LVOT
      abnormality or DOLAVV. High insertion of the anterolateral papillary muscle was a
      risk factor for death or residual LVOT obstruction. Abnormal LVOT measurements
      were found in patients with tunnel obstruction and those with an acquired
      subaortic ridge. CONCLUSIONS: Transthoracic echocardiography provides accurate
      preoperative information on AVSD.

PMID- 11451284
TI  - Markedly reduced insulin-like growth factor-1 in the acute phase of myocardial
      infarction.
AB  - OBJECTIVES: We investigated whether insulin-like growth factor-1 (IGF-1) is
      reduced in the early phase of acute myocardial infarction (AMI) and whether such
      a decrease might influence prognosis. BACKGROUND: Insulin-like growth factor-1
      protects against insulin resistance and apoptosis. Although insulin resistance
      has been reported in AMI, IGF-1 levels have not been investigated. METHODS: We
      measured serum IGF-1 in 23 patients with AMI within 24 h of symptom onset and in
      11 matched controls. In the first 12 patients and controls, we also measured
      fasting insulin, diurnal growth hormone (GH) and insulin sensitivity (assessed as
      glucose disappearance or T/2 after an insulin bolus), and repeated IGF-1, insulin
      and GH after one year. In all patients, 90-day cardiovascular death, recurrent
      ischemia, reinfarction, revascularization and late malignant arrhythmias were
      assessed. RESULTS: The AMI patients versus controls showed markedly reduced IGF-1
      (115 +/- 112 vs. 615 +/- 300 ng/ml, p < 0.0001) and slower T/2 (-0.98 +/- 1.5 vs.
      -2.57 +/- 1.0 mg/dl/min, p = 0.01). Low IGF-1 often preceded the rise of
      myocardial necrosis markers. Patients with 90-day events (n = 12) versus those
      without had lower IGF-1 (47 +/- 54 vs. 189 +/- 110 ng/ml, p < 0.0001). Acute
      phase GH and insulin concentrations did not differ significantly from controls.
      After one year, the patients' IGF-1 values had risen to 460 +/- 242 ng/ml (p =
      0.1 vs. controls, p < 0.0005 vs. acute phase), whereas GH levels were lower (0.2
      +/- 0.2 vs. 2.5 +/- 2.3 ng/ml, p = 0.01) and insulin levels higher (12.5 +/- 0.2
      vs. 3.9 +/- 2.6 microU/ml, p < 0.0001) compared with controls. CONCLUSIONS: In
      the early phase of AMI, serum IGF-1 levels are markedly reduced and may
      contribute to adverse outcomes. Reduced IGF-1 preceding the rise of myocardial
      necrosis markers suggests a possible pathogenetic role. A compensatory increase
      in IGF-1 appears to occur by one year.

PMID- 11451285
TI  - Magnetic resonance phase-shift velocity mapping in pediatric patients with
      pulmonary venous obstruction.
AB  - OBJECTIVES: This study evaluated the accuracy, advantages and clinical efficacy
      of magnetic resonance (MR) phase-shift velocity mapping, in delineating the site
      and the hemodynamic severity of pulmonary venous (PV) obstruction in patients
      with congenital heart disease (CHD). BACKGROUND: Magnetic resonance phase-shift
      velocity mapping of normal pulmonary veins and of obstructed PV pathways have
      been previously reported in a mainly adult population. METHODS: The study
      population (33 pts) underwent MR phase-shift velocity mapping of their PV
      pathways. These results were compared with cardiac catheterization and Doppler
      echocardiography data. RESULTS: The study population (0.4 to 19.5 years)
      consisted of a study group (PV pathway obstruction, n = 7) and a control group
      (no PV obstruction, n = 26). No patients had any left-to-right shunt lesions. The
      MR imaging displayed precise anatomical detail of the pulmonary veins. Phase
      velocities in the control group ranged from 20 to 71 cm/s, whereas velocities in
      the study group ranged from 100 to 250 cm/s (p = 0.002). The MR phase velocities
      (154 +/- 0.53 cm/s) compared favorably with Doppler echocardiography (147 +/-
      0.54 cm/s), (r = 0.76; p = 0.05). The MR velocity mapping was 100% specific and
      100% sensitive in detecting PV obstruction, although the absolute gradient
      measurements among MR phase mapping, echocardiographic Doppler and
      catheterization did not show statistically significant correlation. CONCLUSIONS:
      In the absence of any associated left-to-right shunt lesions, PV velocities of
      100 cm/s and greater indicated significant obstruction. The MR phase-shift
      velocity mapping, together with MR spin echocardiography and MR angiography,
      provides comprehensive anatomic and physiologic data that may obviate the need
      for further invasive studies.

PMID- 11451286
TI  - Issues and ethics of the hiring of cardiothoracic surgeons by cardiology
      practices.

PMID- 11451287
TI  - President's page: forging change in health care policy--the principle is the
      thing.

PMID- 11451288
TI  - Batista's operation: what have we learned?

PMID- 11451289
TI  - A randomized trial of multivessel stent versus coronary bypass.

PMID- 11451290
TI  - Lean tissue adjusted peak oxygen consumption in congestive heart failure.

PMID- 11451291
TI  - Space and time dependency of inertial and convective contribution to the
      transmitral pressure drop during ventricular filling.

PMID- 11451292
TI  - Paclitaxel-coated stent: is there a light at the end of the tunnel?

PMID- 11451293
TI  - Time course of cardiac structural, functional and electrical changes in
      asymptomatic patients after myocardial infarction: their inter-relation and
      prognostic impact.
AB  - OBJECTIVES: We prospectively studied the relationship between left ventricular
      (LV) dilation, dysfunction, electrical instability and death in patients after a
      first myocardial infarction (MI) without symptoms of heart failure and ischemia.
      BACKGROUND: Mechanisms linking LV dysfunction and sudden death in patients after
      MI remained controversial. METHODS: Left ventricular volumes, hemodynamics,
      electrocardiogram and 24-h Holter recordings were sequentially obtained between
      two days and seven years after MI. Left ventricular catheterization and coronary
      angiography were performed, and revascularization was performed if appropriate.
      RESULTS: Death occurred in 16 (12%) of the 134 patients included; it was of
      cardiac origin in 14 (88%) and sudden in origin in 12 (75%) patients. Of 37 (28%)
      patients with LV dilation, 12 died (32%); four patients (5.8%) died in the group
      without dilation. Left ventricular dilation was closely related to signs of
      electrical instability, as indicated by a significant correlation between end
      diastolic LV volume index, Lown score (r = 0.98, p < 0.0001) and QTc prolongation
      (r = 0.998, p < 0.01), respectively. CONCLUSIONS: Patients with progressive
      remodeling are at increased risk of sudden death in chronic MI. Cardiac
      electrical instability is closely related to progressive LV dilation. Parameters
      of electrical instability and remodeling are predictors of sudden death. The
      findings suggest that remodeling might serve as a link between dysfunction,
      electrical instability of the heart and sudden death after MI.

PMID- 11451294
TI  - Is early invasive treatment of unstable coronary artery disease equally effective
      for both women and men? FRISC II Study Group Investigators.
AB  - BACKGROUND: The Fragmin and fast Revascularization during InStability in Coronary
      artery disease (FRISC II) trial compared the effectiveness of an early invasive
      versus a noninvasive strategy in terms of the incidence of death and myocardial
      infarction (MI) in patients with unstable coronary artery disease (CAD).
      OBJECTIVES: In this subanalysis, we sought to evaluate gender differences in the
      effect of these different strategies. METHODS: The patients (749 women and 1,708
      men) were randomized to early invasive or noninvasive strategies. Coronary
      angiography was performed within the first 7 days in 96% and 10% of the invasive
      and noninvasive groups, respectively, and revascularization was performed within
      the first 10 days in 71% and 9% of the invasive and noninvasive groups,
      respectively. RESULTS: Women presenting with unstable CAD were older, but fewer
      had previous infarctions, left ventricular dysfunction and elevated troponin T
      levels. Women had fewer angiographic changes. There was no difference in MI or
      death at 12 months among women in the invasive and noninvasive groups (12.4% vs.
      10.5%, respectively), in contrast to the favorable effect in the invasively
      treated group of men (9.6% vs. 15.8%, p < 0.001). In an interaction analysis,
      there was a different effect of the early invasive strategy for the two genders
      (p = 0.008). CONCLUSIONS: Women with symptoms and/or signs of unstable CAD are
      older, but still have less severe CAD and a better prognosis compared with men.
      In contrast to its beneficial effect in men, an early invasive strategy did not
      reduce the risk of future events among women. Further research is warranted to
      identify the most appropriate treatment strategy in women with unstable CAD.

PMID- 11451295
TI  - Activation of cardiac renin-angiotensin system in unstable angina.
AB  - OBJECTIVES: The aim of this study was to investigate the activity of the cardiac
      renin-angiotensin system (RAS) in unstable angina (UA). BACKGROUND: Angiotensin
      (Ang) II locally produced by continuously operating cardiac RAS may affect the
      pathophysiology of UA. METHODS: In 35 patients with UA, 32 with stable effort
      angina (SA) and 21 with atypical chest pain (controls), cardiac RAS was
      investigated during coronary angiography after five days of Holter monitoring by
      combining the measurement of aorta-coronary sinus gradient for Ang I and Ang II
      with the kinetics study of 125I-Ang I. Messenger RNAs (mRNA) for all the
      components of RAS were also quantified with the reverse transcriptase-polymerase
      chain reaction (RT-PCR) and localized by in situ hybridization in myocardial
      biopsy specimens from patients who underwent aorta-coronary bypass surgery.
      RESULTS: Cardiac Ang II generation was higher in patients with UA than it was in
      patients with SA or in controls (p < 0.001) due to increased de novo cardiac Ang
      I formation and its enhanced fractional conversion rate to Ang II. Messenger RNA
      levels for angiotensinogen (AGTN), angiotensin-converting enzyme (ACE) and Ang II
      type 1 (AT1) subtype receptors were higher in patients with UA (p < 0.01) than
      they were in patients with SA or in control hearts. Messenger RNAs for AGTN and
      ACE were almost exclusively expressed on endothelial and interstitial cells.
      Angiotensin II formation was correlated with ischemia burden (p < 0.001).
      However, the amount of Ang II formed and the expression levels of mRNAs for AGTN,
      ACE and AT1 were not related to the time that had elapsed since the last anginal
      attack. CONCLUSIONS: In patients with UA, cardiac RAS is activated, resulting in
      increased Ang II formation. Myocardial ischemia is essential for RAS activation,
      but it is unlikely to be a direct and immediate cause of RAS activation.

PMID- 11451296
TI  - Long-term risk stratification for survivors of acute coronary syndromes. Results
      from the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID)
      Study. LIPID Study Investigators.
AB  - OBJECTIVES: We developed a prognostic strategy for quantifying the long-term risk
      of coronary heart disease (CHD) events in survivors of acute coronary syndromes
      (ACS). BACKGROUND: Strategies for quantifying long-term risk of CHD events have
      generally been confined to primary prevention settings. The Long-term
      Intervention with Pravastatin in Ischemic Disease (LIPID) study, which
      demonstrated that pravastatin reduces CHD events in ACS survivors with a broad
      range of cholesterol levels, enabled assessment of long-term prognosis in a
      secondary prevention setting. METHODS: Based on outcomes in 8,557 patients in the
      LIPID study, a multivariate risk factor model was developed for prediction of CHD
      death or nonfatal myocardial infarction. Prognostic indexes were developed based
      on the model, and low-, medium-, high- and very high-risk groups were defined by
      categorizing the prognostic indexes. RESULTS: In addition to pravastatin
      treatment, the independently significant risk factors included: total and high
      density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS,
      prior coronary revascularization, diabetes mellitus, hypertension and prior
      stroke. Pravastatin reduced coronary event rates in each risk level, and the
      relative risk reduction did not vary significantly between risk levels. The
      predicted five-year coronary event rates ranged from 5% to 19% for those assigned
      pravastatin and from 6.4% to 23.6% for those assigned placebo. CONCLUSIONS: Long
      term prognosis of ACS survivors varied substantially according to conventional
      risk factor profile. Pravastatin reduced coronary risk within all risk levels;
      however, absolute risk remained high in treated patients with unfavorable
      profiles. Our risk stratification strategy enables identification of ACS
      survivors who remain at very high risk despite statin therapy.

PMID- 11451297
TI  - Prognostic value of ST segment depression in acute coronary syndromes: insights
      from PARAGON-A applied to GUSTO-IIb. PARAGON-A and GUSTO IIb Investigators.
      Platelet IIb/IIIa Antagonism for the Reduction of Acute Global Organization
      Network.
AB  - OBJECTIVES: Our objectives were to develop a risk-stratification model addressing
      the importance of the magnitude and distribution of ST segment depression in
      predicting long-term outcomes and to validate the model in an analogous patient
      population. BACKGROUND: Although patients without ST segment elevation presenting
      with acute coronary syndromes represent an increasingly frequent population
      admitted to coronary care units, little attention has been paid to quantifying
      their ST segment abnormalities. METHODS: ST segment depression was categorized
      into three groups: 1) no ST segment depression; 2) 1-mm ST segment depression in
      two contiguous leads; and 3) ST segment depression > or =2 mm in two contiguous
      leads. A logistic regression model was developed using Platelet IIb/IIIa
      Antagonism for the Reduction of Acute coronary syndrome events in a Global
      Organization Network (PARAGON-A) data to assess the prognostic value of the
      extent and distribution of ST segment depression in predicting one-year
      mortality. The model was validated using the non-ST segment elevation population
      in Global Use of Strategies To Open occluded arteries in acute coronary syndromes
      (GUSTO-IIb). RESULTS: ST segment depression was the strongest predictor of one
      year mortality, accounting for 35% of the model's predictive power. Patients with
      ST segment depression > or =2 mm were approximately 6 times (odds ratio [OR]
      5.73, 95% confidence interval [CI] 2.8 to 11.6) more likely to die within one
      year than patients with no ST segment depression. On validation, the model showed
      good discriminatory power (c-index = 0.75). Patients with ST segment depression >
      or =2 mm in more than one region were almost 10 times more likely to die within
      one year than patients with no ST segment depression. CONCLUSIONS: These data
      provide new evidence supporting the powerful prognostic value of the baseline
      electrocardiogram and, in particular, the magnitude and distribution of ST
      segment depression in predicting unfavorable events.

PMID- 11451298
TI  - Exercise-induced silent myocardial ischemia and coronary morbidity and mortality
      in middle-aged men.
AB  - OBJECTIVES: We investigated the prognostic significance of exercise-induced
      silent myocardial ischemia in both high and low risk men with no prior coronary
      heart disease (CHD). BACKGROUND: Silent ischemia predicts future coronary events
      in patients with CHD, but there is little evidence of its prognostic significance
      in subjects free of CHD. METHODS: We investigated the association of silent
      ischemia, as defined by ST depression during and after maximal symptom-limited
      exercise test, with coronary risk in a population-based sample of men with no
      prior CHD followed for 10 years on average. RESULTS: Silent ischemia during
      exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in
      smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold
      (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The
      respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7
      to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations
      were weaker in men without these risk factors. Furthermore, silent ischemia after
      exercise was a stronger predictor for the risk of acute coronary events and CHD
      death in smokers and in hypercholesterolemic and hypertensive men than in men
      without risk factors. CONCLUSIONS: Exercise-induced silent myocardial ischemia
      was a strong predictor of CHD in men with any conventional risk factor,
      emphasizing the importance of exercise testing to identify asymptomatic high risk
      men who could benefit from risk reduction and preventive measures.

PMID- 11451299
TI  - Postmenopausal hormones and heart disease.

PMID- 11451300
TI  - Silent ischemia predicts poor outcome in high-risk healthy men.

PMID- 11451301
TI  - Relation of thallium uptake to morphologic features of chronic ischemic heart
      disease: evidence for myocardial remodeling in noninfarcted myocardium.
AB  - OBJECTIVES: The aim of this study was to investigate the disparity between the
      extent of myocardial injury as assessed by thallium and the severity of left
      ventricular (LV) dysfunction in chronic ischemic heart disease. BACKGROUND:
      Although it is believed that thallium differentiates between viable and nonviable
      myocardium, in some patients with chronic ischemic heart disease, viable regions
      by thallium may fail to improve function after revascularization. METHODS:
      Thirteen transplant candidates with chronic ischemic heart disease (LV ejection
      fraction = 14 +/- 6% at rest) were studied prospectively with stress
      redistribution-reinjection thallium single-photon emission computed tomography.
      We examined pretransplantation quantitative thallium uptake and post
      transplantation extent and the histological distribution of collagen replacement
      in infarcted and noninfarcted myocardium and in 13 age-matched control hearts.
      RESULTS: The volume fraction of collagen varied inversely with wall thickness (r
      = -0.70, p < 0.001) and was higher in irreversible (30.9 +/- 15.8%) compared with
      reversible (20.2 +/- 12.6%, p < 0.001) or normal thallium segments (15.0 +/-
      8.7%, p < 0.001). The irreversible thallium segments had lower wall thickness and
      more severe coronary artery narrowing (9.7 +/- 2.8 mm and 95 +/- 8%) compared
      with reversible (11.7 +/- 2.7 mm and 87 +/- 13%, p < 0.001) and normal thallium
      segments (12.8 +/- 2.6 mm and 80 +/- 14%, p < 0.001). Mean volume fraction of
      collagen was significantly lower in noninfarcted than it was in infarcted
      segments (13 +/- 6% vs. 36 +/- 13%, p < 0.001) but exceeded that in the control
      hearts (4 +/- 2%, p < 0.001). Noninfarcted segments had predominantly
      interstitial fibrosis with either microscopic or patchy areas of replacement
      fibrosis. CONCLUSIONS: In chronic ischemic heart disease with severe LV
      dysfunction, patterns of normal, reversible and irreversible thallium uptake
      correlated with the magnitude of collagen replacement, segmental wall thickness
      and severity of coronary artery narrowing. The finding of scattered areas of
      replacement fibrosis in noninfarcted myocardium may explain the observed
      disparity between LV contractile dysfunction and the extent of myocardial injury
      assessed by thallium.

PMID- 11451302
TI  - Myocardial viability assessment by endocardial electroanatomic mapping:
      comparison with metabolic imaging and functional recovery after coronary
      revascularization.
AB  - OBJECTIVES: The objective of this study was to compare electroanatomic mapping
      for the assessment of myocardial viability with nuclear metabolic imaging using
      positron emission computed tomography (PET) and with data on functional recovery
      after successful myocardial revascularization. BACKGROUND: Animal experiments and
      first clinical studies suggested that electroanatomic endocardial mapping
      identifies the presence and absence of myocardial viability. METHODS: Forty-six
      patients with prior (> or =2 weeks) myocardial infarction underwent fluorine-18
      fluorodeoxyglucose (FDG) PET and Tc-99m sestamibi single-photon emission computed
      tomography (SPECT) before mapping and percutaneous coronary revascularization.
      The left ventricular endocardium was mapped and divided into 12 regions, which
      were assigned to corresponding nuclear regions. Functional recovery using the
      centerline method was assessed in 25 patients with a follow-up angiography.
      RESULTS: Regional unipolar electrogram amplitude was 11.0 mV +/- 3.6 mV in
      regions with normal perfusion, 9.0 mV +/- 2.8 mV in regions with reduced
      perfusion and preserved FDG-uptake and 6.5 mV +/- 2.6 mV in scar regions (p <
      0.001 for all comparisons). At a threshold amplitude of 7.5 mV, the sensitivity
      and specificity for detecting viable (by PET/SPECT) myocardium were 77% and 75%,
      respectively. In infarct areas with electrogram amplitudes >7.5 mV, improvement
      of regional wall motion (RWM) from -2.4 SD/chord +/- 1.0 SD/chord to -1.5
      SD/chord +/- 1.1 SD/chord (p < 0.01) was observed, whereas, in infarct areas with
      amplitudes <7.5 mV, RWM remained unchanged at follow-up (-2.3 SD/chord +/- 0.7
      SD/chord to -2.4 SD/chord +/- 0.7 SD/chord). CONCLUSIONS: These data suggest that
      the regional unipolar electrogram amplitude is a marker for myocardial viability
      and that electroanatomic mapping can be used for viability assessment in the
      catheterization laboratory.

PMID- 11451303
TI  - Mechanical and structural characteristics of vulnerable plaques: analysis by
      coronary angioscopy and intravascular ultrasound.
AB  - OBJECTIVES: Mechanical and structural characteristics of vulnerable plaques were
      evaluated using coronary angioscopy and intravascular ultrasound. BACKGROUND:
      Mechanical stress and composition of plaques play an important role in plaque
      disruption. METHODS: Thirty-eight lesions in 38 patients were examined pre
      interventionally. The plaques were classified as either yellow or white using
      coronary angioscopy. Intravascular ultrasound imaging was performed
      simultaneously with electrocardiographic and intracoronary pressure recordings to
      calculate distensibility index and stiffness beta. Moreover, the type of
      remodeling was classified. RESULTS: We identified 27 patients with yellow plaques
      and 11 patients with white plaques. Patients with yellow plaques presented acute
      coronary syndromes more frequently than stable angina (85% vs. 36%, p < 0.01).
      The distensibility index in yellow plaques was significantly greater than it was
      in white plaques (2.7 +/- 0.8 mm Hg(-1) vs. 0.7 +/- 0.8 mm Hg(-1), p < 0.0001),
      while stiffness beta for white plaques was significantly greater than it was for
      yellow plaques (34.9 +/- 16.3 vs. 8.7 +/- 2.7, p < 0.0001). Compensatory
      enlargement occurred more frequently with yellow plaques than with white plaques
      (56% vs. 9%, p < 0.01), while paradoxical shrinkage occurred more frequently with
      white plaques than it did with yellow plaques (64% vs. 4%, p < 0.001).
      CONCLUSIONS: Yellow plaques with an increased distensibility and a compensatory
      enlargement may be mechanically and structurally weak. As a result, mechanical
      "fatigue," caused by repetitive stretching, may lead to plaque disruption.
      Plaques with a high distensibility and a compensatory enlargement may be
      vulnerable.

PMID- 11451304
TI  - Follow the eyes.

PMID- 11451305
TI  - Predicting physical therapy visits needed to achieve minimal functional goals
      after arthroscopic knee surgery.
AB  - STUDY DESIGN: Retrospective, cross-sectional regression modeling. OBJECTIVE: To
      predict physical therapy visits following arthroscopic knee surgery. BACKGROUND:
      The number of physical therapy visits required to achieve a set of specific
      minimal-level goals (full knee extension, straight leg raise, normalized gait
      pattern, bicycle pedaling, and independent home exercises) that are related to
      decreased complication rates has not previously been modeled. METHODS AND
      MEASURES: A multiple regression model to predict postoperative physical therapy
      visits was developed using subject demographics and 2 simple clinical measures,
      degree of straight leg raise lag and total range of motion. All data were
      collected from 148 patient charts. Model validity was examined by the predicted
      residual sum of squares technique and a second independent sample of 157 charts.
      RESULTS: Diagnosis group, surgery group, and range of motion were the significant
      variables predicting visits in the final model (R2 = 0.384). Results of model
      validation analyses using predicted residual sum of squares technique (R2 =
      0.346) and the second set of data (R2 = 0.282) were satisfactory. Analysis of
      residuals (difference of observed and predicted visits) showed prediction of the
      number of physical therapy visits within 3 visits for approximately 75% of the
      cases in both sets of data. CONCLUSIONS: Using the model to predict physical
      therapy visits following arthroscopic knee surgery was more accurate than using
      diagnosis alone, except for lateral retinacular release. This study demonstrates
      how regression models could be used to explain variance in physical therapy
      visits for a given set of minimal functional goals.

PMID- 11451306
TI  - Transient osteoporosis of the hip associated with pregnancy.

PMID- 11451307
TI  - Reliability of the lateral pull test and tilt test to assess patellar alignment
      in subjects with symptomatic knees: student raters.
AB  - STUDY DESIGN: Test-retest reliability with blinded testers. OBJECTIVES: To
      determine the inter- and intra-rater reliability of the lateral pull test and
      patellar tilt test. BACKGROUND: If patellar malalignment can be detected by
      clinical examination, then condition-specific treatment interventions may be
      implemented in patients with patellofemoral pain syndrome. However, several
      clinical tests used to assess patellar mobility have recently been shown to have
      poor to fair reliability. Because the lateral pull test and the patellar tilt
      test are widely used clinically as diagnostic tests for patellofemoral pain
      syndrome but have not been previously tested for reliability, we examined these
      tests. METHODS AND MEASURES: Fifty-two subjects (age range, 21-48 years) provided
      95 knees (19 symptomatic and 76 asymptomatic) for assessment of the lateral pull
      test. Two testers, blinded to the presence or absence of symptoms, independently
      performed the lateral pull test in random order. Fifty-five subjects (age range,
      22-42 years) provided 99 knees (73 asymptomatic and 26 symptomatic) for
      assessment of the patellar tilt test. Three blinded testers independently
      performed the patellar tilt test in random order. All subjects were tested and
      retested within 3-5 days. A kappa (kappa) statistic was used to assess the
      agreement of findings within each tester and between testers. RESULTS: The kappa
      coefficients for intrarater reliability varied from 0.39 to 0.47 for the lateral
      pull test and from 0.44 to 0.50 for the patellar tilt test, while the
      coefficients for interrater reliability were 0.31 for the lateral pull test and
      varied from 0.20 to 0.35 for the tilt test. CONCLUSIONS: Repeated lateral pull
      tests and patellar tilt tests had fair intrarater and poor interrater
      reliability. Our results suggest that care must be taken in placing too much
      emphasis on these tests when making clinical decisions.

PMID- 11451308
TI  - Postures and repetitive movements during use of a long cane by individuals with
      visual impairment.
AB  - STUDY DESIGN: Descriptive. OBJECTIVE: To describe upper body postures and
      movements that occur when an individual with visual impairment uses a cane to
      explore the environment while walking. BACKGROUND: Previous research revealed
      self-reported neuromusculoskeletal problems related to cane use in individuals
      with visual impairments. No research, however, is available correlating
      neuromusculoskeletal problems with specific strategies of cane use or describing
      what movements and postures actually occur during cane use. METHODS AND MEASURES:
      Twenty-eight individuals with visual impairment who had been walking
      independently with a long cane for >1 year were videotaped walking with their
      canes. Subjects included 16 men and 12 women with a mean age of 39.8 +/- 15.2.
      Postures and movements of the head and neck, trunk, and each upper extremity body
      segment were analyzed using videotape. RESULTS: Thirty-nine categories of
      postures or repetitive joint movements were observed. Half of the subjects lacked
      intersegmental movement of the head, trunk, and shoulder girdles during walking.
      The repetitive movements used to manipulate the cane occurred at the forearm or
      wrist. Intrasubject variability of postures and movements was low. CONCLUSIONS: A
      variety of sustained postures and repetitive movements occur among individuals
      using long canes. Each individual displays minimal variability in cane
      manipulation strategy when walking in an uncomplicated environment. Cane
      manipulation is accomplished by repetitive movements of wrist flexion/extension,
      wrist ulnar/radial deviation, or forearm pronation/supination. The remainder of
      the upper body maintains sustained postures, and more than half of long cane
      users lack the normal intersegmental movement that typically occurs in the neck,
      trunk, and shoulder girdle during walking. Further research is needed to
      determine whether particular cane manipulation strategies or sustained postures
      during cane use increase the risk of musculoskeletal pain syndromes.

PMID- 11451309
TI  - Comparison of acute swelling and function in subjects with lateral ankle injury.
AB  - STUDY DESIGN: Prospective correlational study involving a convenience sample.
      OBJECTIVES: To investigate the relationships among figure-of-eight girth
      measurements and functional level in patients with acute lateral ankle sprains to
      determine the appropriate use of these clinical measures. BACKGROUND: Research
      has shown that subjective scales of perceived athletic ability and measurements
      of swelling are useful in assessing clinical improvement following an acute ankle
      sprain; however, the relationship between ankle swelling and level of function is
      not known. METHODS AND MEASURES: Twenty-nine subjects (20 men, 9 women) varying
      in age from 18-59 years of age (mean age, 30.8 +/- 11.37) with acute lateral
      ankle sprains were included in this study. Each subject was evaluated by 1 of 3
      raters for ankle girth, weight-bearing status, and functional level as determined
      by a modified Ankle Osteoarthritis Scale (AOS) and the Foot and Ankle Ability
      Index (FAAI). This study also investigated the relationship between these
      measures and the sport subscale of the FAAI (FAAI sport). This is an 8-item
      subscale which includes questions on running, jumping, landing, quick starts and
      stops, cutting or lateral movements, low impact activities, ability to perform an
      activity with normal technique, and ability to participate in desired sports.
      RESULTS: No significant correlations were found between figure-of-eight girth
      measurements and functional level. However, we did find moderate to good
      correlations between the FAAI vs. weight-bearing (rho = 0.73), FAAI vs. AOS (rho
      = -0.79), FAAI sport vs. weight-bearing (rho = 0.68), FAAI vs. FAAI Sport (rho =
      0.73), weight-bearing vs. AOS (rho = -0.57), and FAAI Sport vs. AOS (rho = 
      0.50). CONCLUSIONS: The figure-of-eight method is highly reliable and is
      appropriate for measuring ankle swelling; however, it does not correlate with
      functional level as determined by the modified AOS, FAAI, or observed weight
      bearing status during gait. Therefore, clinicians should refrain from making
      assumptions about function based on ankle swelling.

PMID- 11451310
TI  - What's new in trichothiodystrophy.

PMID- 11451311
TI  - Familial scleroderma: do environmental factors, genes and microchimerism share
      the same relevance?

PMID- 11451312
TI  - Persistent pigmented purpuric dermatoses: who are you?

PMID- 11451313
TI  - The prevalence of psoriasis in the world.

PMID- 11451314
TI  - Can we still suggest the topical cyclosporin treatment in cutaneous disorders?

PMID- 11451315
TI  - Prevalence of psoriasis in Spain (Epiderma Project: phase I).
AB  - BACKGROUND: Various national and international studies are under way to obtain
      reliable data on the epidemiological features of psoriasis. OBJECTIVES: The
      purpose of this study was to determine the prevalence of psoriasis in the general
      population in Spain as well as its variations according to sex, age and
      distribution in different geographical areas. MATERIAL AND METHODS: A random
      sample (12,938 subjects from 4027 households), representative of the general
      population, was the basis for a cross-sectional survey through telephone calls
      performed by trained non-medical interviewers using a specific questionnaire.
      RESULTS: The prevalence of psoriasis, similar in both sexes, was estimated to be
      1.17-1.43%. The highest prevalence rates were shown among 20-50-year-old
      subjects. Distribution of psoriatic patients was not homogeneous throughout the
      country and prevalence was shown to be higher in the central dry region of the
      country. CONCLUSIONS: In a population of about 40 million inhabitants, 470,000
      570,000 psoriatic subjects constitute an important target for health care issues
      and further epidemiological studies.

PMID- 11451316
TI  - Dermoscopy as a second step in the diagnosis of doubtful pigmented skin lesions:
      how great is the risk of missing a melanoma?
AB  - BACKGROUND: Little is known about the occurrence of false negatives in the
      diagnosis of melanoma using dermoscopy in clinical practice: in the literature
      dermoscopy only increased the accuracy of diagnosis of equivocal lesions that
      were to undergo biopsy anyway. AIM AND METHODS: We collected the 81 lesions
      clinically diagnosed as probable melanomas by experienced specialists (from a
      series of 256 pigmented skin lesions submitted to excisional biopsy) and reviewed
      them for possible false negative results in the diagnosis of melanoma using in
      vivo dermoscopy and dermoscopy performed on slide images. Both procedures were
      carried out by the same experienced dermatologists who classified the lesions
      clinically. RESULTS: Dermoscopy made on slide images (observers blinded for
      clinical features of the lesions) yielded three false negative results (91%
      sensitivity) in a group of 35 histologically confirmed melanomas. In vivo
      dermoscopy showed better results, with no melanomas missed (100% sensitivity).
      The frequency of false positive results in the diagnosis of melanoma was 13.5%
      (11 of 81) with dermoscopy on slide images and 2.5% (two of 81) with in vivo
      dermoscopy. CONCLUSIONS: Only in vivo dermoscopy by fully trained dermatologists
      with both clinical and dermoscopic experience avoids the risk of
      misclassification of melanomas otherwise correctly classified on clinical
      grounds.

PMID- 11451317
TI  - The acetowhite test in genital human papillomavirus infection in men: what does
      it add?
AB  - BACKGROUND: Many genital human papillomavirus (HPV) infections are clinically
      invisible epithelial lesions. They remain so for a considerable time before some
      develop into clinically apparent lesions. The inapparent and asymptomatic nature
      of these lesions poses a problem in the detection and management of genital HPV
      infection. Without reliable, and readily available diagnostic methods, no
      definite therapeutic approach can be recommended or followed. The acetowhite test
      has been recommended to help determine the extent of the affected area.
      OBJECTIVE: To evaluate the acetowhite test in detecting inapparent subclinical
      HPV involvement in male patients with clinically apparent warts. METHODS: Two
      hundred and two uncircumcised patients with genital warts were included. Patients
      with concomitant inflammatory lesions were excluded. The warts and adjacent
      normal skin/mucosa of normal appearance were wrapped in gauze soaked in 5% acetic
      acid for about 3-5 min. The area was subsequently examined with a hand lens (x
      8). RESULTS: All of the 116 hyperplastic warts became acetowhite, as well as a
      narrow rim of surrounding skin. Few flat warts in dry areas only became dull
      white and none pure white. No whiteness was observed in the surrounding area.
      Only 15 of 26 flat warts in moist areas became acetowhite. One (eroded lesion) of
      13 verruca vulgaris type lesions and none of the pigmented papules gave positive
      results to the acetowhite test. CONCLUSIONS: The sensitivity of the acetowhite
      test for hyperplastic warts is very high, but for other types of warts is low.
      Detection of subclinical HPV-infected areas is difficult; the acetowhite test did
      not assist in the identification of additional areas of infection in our
      patients.

PMID- 11451318
TI  - Cohort study of metastatic melanoma patients in the Dermatology Institute of
      Florence 1990/1997.
AB  - BACKGROUND: Chemotherapy and immunotherapy are treatments currently employed in
      advanced melanoma, but responses obtained are poor, and metastatic melanoma
      patients with visceral localization rarely survive for more than 6 months. Thus,
      different therapeutic regimens are used in metastatic melanoma and no
      standardized therapy exists so far. METHODS: We report a retrospective survival
      study involving 80 patients with metastatic melanoma who were treated either with
      chemotherapy [dacarbazine (DTIC) alone or DTIC in monotherapeutic or
      polychemotherapeutic regimen] or immunochemotherapy [interferon (IFN)-alpha at
      low doses added to chemotherapy]. Survival of patients was statistically
      evaluated in an actuarial curve taking into account as predictive variables sex,
      age, marital status, site of primary tumour, histological type, Clark level,
      sites of metastases, and the different therapeutic regimens (i.e. DTIC alone,
      DTIC plus IFN-alpha, or others, with or without IFN-alpha). RESULTS: Site of
      primary melanoma, histological type, Clark level and therapy regimen appeared to
      exhibit a prognostic significance in survival; when a multivariate analysis was
      performed to obtain a mutual adjustment of survival values for each variable,
      only the therapeutic regimen was found to be significant as an independent
      prognostic variable. Patients treated with immunochemotherapy, i.e. DTIC plus IFN
      alpha, showed a probability of dying of 0.41 (95% confidence interval 0.2-0.8)
      compared with patients treated with DTIC alone. CONCLUSIONS: In our study
      immunochemotherapy, comprised of DTIC plus IFN-alpha at low doses, was associated
      with a significantly longer survival of patients, in comparison with chemotherapy
      comprised of only DTIC.

PMID- 11451319
TI  - Systemic ketoconazole for yeast allergic patients with atopic dermatitis.
AB  - BACKGROUND: Adult patients with atopic dermatitis (AD), especially with the head
      neck distribution, are often sensitized to the lipophilic yeast Malassezia
      furfur/Pityrosporum orbiculare, which is considered to contribute to the
      pathogenesis of the dermatitis. OBJECTIVE: Evaluation of the efficacy of oral
      ketoconazole on immunological and clinical parameters in yeast allergic adult
      patients with AD. STUDY DESIGN: Randomized double-blind placebo-controlled study.
      SUBJECTS: Twenty-nine patients with specific IgE antibodies to M. furfur/P.
      orbiculare and with elevated serum IgE participated in the investigation. Fifteen
      subjects were treated with 200 mg ketoconazole daily and 14 received placebo for
      3 months. Betamethasone cream was allowed as supplementary therapy and the
      consumption was registered. The clinical score (SCORAD), total serum IgE and
      specific IgE antibodies to M. furfur/P. orbiculare, Candida albicans and
      Dermatophagoides pteronyssinus were monitored at the starting point and by the
      end of the first and third month. RESULTS: In the actively treated group the
      levels of specific IgE to M. furfur/P. orbiculare and C. albicans as well as
      total serum IgE decreased significantly. Sensitization to D. pteronyssinus was
      not influenced. The clinical score decreased in both groups, and the improvement
      was correlated to the consumption of topical steroids in the control group but
      not in the ketoconazole group.

PMID- 11451320
TI  - Lentiginous macules and patches of neurofibromatosis (an approach to better
      terminology).
AB  - BACKGROUND AND OBJECTIVES: Freckles (ephelides) are small, light brown macules of
      sun-exposed areas in fair-skinned subjects. On the other hand, freckle-like
      pigmentation of the axilla is a highly characteristic feature of
      neurofibromatosis. To what extent (clinically and pathologically) are the two
      pigmentary defects similar? And to what extent are cafe-au-lait patches and
      freckle-like lesions similar pathologically? SUBJECTS AND METHODS: Ten cases of
      neurofibromatosis and 10 cases of freckles were examined clinically. Two biopsies
      were taken from the former; one obtained from an axillary freckle-like lesion,
      and the other from a cafe-au-lait patch. One biopsy only was taken from freckles.
      The biopsies were processed for haematoxylin and eosin, silver stain and
      transmission electron microscopy. RESULTS: Obvious differences were detected
      between freckles (ephelides) and freckle-like lesions in cases of
      neurofibromatosis. Cafe-au-lait patches and freckle-like lesions showed the same
      pathological changes of lentigo simplex, with increased melanin pigment from the
      basal layer up to the stratum corneum, moderate elongation of the rete ridges and
      mild inflammatory infiltrate intermingled with melanophages. Electron microscopy
      revealed an increase in melanocyte number and the presence of giant melanin
      granules in freckle-like pigmentation as well as cafe-au-lait patches. These
      ultrastructural freckles (ephelides) showed an increase in activity but not the
      number of melanocytes. CONCLUSIONS: The term freckle-like should be changed to
      lentiginous macules of neurofibromatosis. On the other hand, the cafe-au-lait
      patches should be considered as lentiginous patches. Freckles should be
      restricted to sun-exposed areas in fair-skinned persons only.

PMID- 11451321
TI  - Malignant atrophic papulosis (Degos' disease): clinicopathological correlations.
AB  - Malignant atrophic papulosis (MAP) is a rare disease characterized by
      pathognomonic cutaneous lesions and frequently fatal systemic involvement.
      Dermatologists should have a high index of suspicion for systemic complications
      in a patient presenting with MAP. We report a case of malignant atrophic
      papulosis to highlight the clinicopathological features and review this important
      dermatological diagnosis.

PMID- 11451322
TI  - Morphoea in three siblings.
AB  - Atrophoderma of Pasini and Pierini (APP) is an uncommon form of localized
      morphoea that occurs as superficial, hyperpigmented plaques distributed mainly on
      the trunk and proximal part of the limbs. There is little information about the
      influence of genetic and environmental factors on disease susceptibility and
      expression for localized scleroderma, although APP familial cases have been
      reported. We report three siblings without a family history of autoimmune disease
      presenting cutaneous lesions suggesting morphoea (APP variant).

PMID- 11451323
TI  - Atypical familial Papillon-Lefevre syndrome.
AB  - The Papillon-Lefevre syndrome is a rare autosomal recessive disorder.
      Consanguinity seems a notable prerequisite. Papillon-Lefevre syndrome manifests
      in the first 6 months of life with rapidly progressive periodontitis and severe
      alveolar bone destruction leading to early loss of both the deciduous and
      permanent teeth in association with palmo-plantar hyperkeratosis. We present two
      unusual cases of familial Papillon-Lefevre syndrome, one of whom has only late
      onset of mild skin lesions and the other has severe skin lesions and relatively
      mild periodontal disease. A number of other cases recently described have also
      had atypical features.

PMID- 11451324
TI  - Atopic dermatitis: the role of Pityrosporum ovale.

PMID- 11451325
TI  - Superficial white onychomycosis in a 3-year-old human immunodeficiency virus
      infected child.
AB  - BACKGROUND: Superficial white onychomycosis is exceptional in children, although
      a few anecdotal cases have been reported in the literature. On the other hand,
      superficial white onychomycosis and proximal subungual onychomycosis, while
      unusual in the general population, often appear in adult human immunodeficiency
      virus (HlV)-infected persons. CASE REPORT: A 3-year-old girl with vertically
      acquired HIV-1 infection presented superficial white onychomycosis involving the
      second, third, fourth and fifth toes of her left foot, caused by Trichophyton
      rubrum. She was treated with topical amorolfine once a week, with a good response
      within 4 weeks. CONCLUSIONS: We report a case of superficial white onychomycosis
      associated with HIV infection in a 3-year-old girl. To our knowledge, this type
      of onychomycosis has not been previously reported in HIV-infected prepubertal
      children.

PMID- 11451326
TI  - Persistent erythema multiforme: a report of three cases.
AB  - Three cases of persistent erythema multiforme, two of unknown aetiology and one
      precipitated by influenza are reported. Lesions were widespread, mostly atypical
      in appearance and regressed in response to immunosuppressants (systemic steroids
      and/or azathioprine) or, in one case, to dapsone. One patient developed
      erythroderma responding eventually to etretinate. Histology in all patients was
      consistent with the mixed, epidermodermal pattern of erythema multiforme. There
      were no significant laboratory abnormalities nor marked symptomatology apart from
      itching. The persistent form appears to belong to the spectrum of erythema
      multiforme being heterogeneous with respect to inducing stimuli, including viral
      antigens, neoplastic or inflammatory disease or unknown causes. Whenever it is
      possible, treatment should be adjusted depending on the causative agent.

PMID- 11451327
TI  - Disseminated pagetoid reticulosis: plaques and tumoral lesions occurring
      simultaneously in the same patient.
AB  - Disseminated pagetoid reticulosis is considered to have a poor prognosis. Some
      authors regard this disease as an epidermotropic type of mycosis fungoides rather
      than a distinct entity. We report the case of an 83-year-old woman with
      disseminated pagetoid reticulosis who subsequently developed tumoral lesions and
      died soon after the appearance of these tumours. Our case is in agreement with
      findings that disseminated pagetoid reticulosis has an aggressive clinical
      behaviour.

PMID- 11451328
TI  - Persistent pigmented purpuric eruption associated with mycosis fungoides: a case
      report and review of the literature.
AB  - A purpuric eruption may be an unusual early manifestation of mycosis fungoides
      (MF). On the other hand, persistent pigmented purpuric dermatoses (PPPD) may,
      occasionally, evolve to cutaneous T-cell lymphoma. Coexistence of these two
      conditions has been reported, but it is extremely rare. We present the case of an
      elderly woman with a long-standing pruritic, pigmented purpuric eruption. On 1
      year follow-up, histological features suggesting early MF were observed and
      molecular analysis of the rearrangement of T-cell receptor genes revealed
      clonality. Our patient may represent a case of PPPD evolving to MF, a case of MF
      clinically featuring PPPD, or an intermediate condition in a nosological
      continuity extending from PPPD to MF. A persistent pigmented purpuric eruption
      may rarely be a harbinger of cutaneous T-cell lymphoma. Therefore, vigilant long
      term follow-up of PPPD is highly recommended.

PMID- 11451329
TI  - PIBI(D)S: clinical and molecular characterization of a new case.
AB  - The term PIBI(D)S has been used to indicate a rare recessively inherited genetic
      disorder characterized by photosensitivity, mild non-congenital ichthyosis,
      brittle sulphur-deficient hair with trichoschisis (trichothiodystrophy), impaired
      intelligence, occasionally decreased fertility and short stature. To the best of
      our knowledge, about 20 cases have been reported in the literature. Here we
      report the characterization of the hair, brain, ultraviolet sensitivity and DNA
      excision repair defects of a new patient affected by PIBI(D)S. The diagnosis of
      PIBI(D)S syndrome was made in our patient on the basis of the clinical features
      and then confirmed by hair microscopy and biochemical analysis. Our patient has
      increased muscular tone, alteration of the deep tendon reflexes and psychomotor
      retardation, all consistent with hypomyelination of the brain showed by magnetic
      resonance imaging and computed tomography. A deficiency of DNA repair capacity
      was demonstrated in our patient. Furthermore, complementation analysis by cell
      fusion assigned our patient to xeroderma pigmentosum group D. The nucleotide
      excision repair defect of the other reported patients with PIBI(D)S falls
      generally into the same group as xeroderma pigmentosum group D and carry a
      mutation on the same repair gene (XPD). The relationship between these molecular
      characteristics and the clinical spectrum of PIBI(D)S is discussed.

PMID- 11451330
TI  - Uncommon localization or presentation of tinea infection.

PMID- 11451331
TI  - Eosinophilic pustular eruption associated with transdermal fentanyl.
AB  - A 70-year-old man developed a widespread eruption of sterile pustules on normal
      skin, mainly on the trunk, face and base of the limbs, 2 days after application
      of a fentanyl-transdermal therapeutic system (fentanyl-TTS) patch. The eruption
      was not accompanied by fever. The main histopathological finding was an
      intraepidermal pustule filled almost exclusively with eosinophils. Suspension of
      the fentanyl-TTS led to rapid and definitive spontaneous regression of the
      pustules in about 10 days. A similar pustular reaction related temporally to
      fentanyl-TTS administration had appeared several weeks before the current
      eruption.

PMID- 11451332
TI  - Junctional epidermolysis bullosa gravis (Herlitz): diagnostic and genetic
      aspects.
AB  - We report on a boy suffering from lethal junctional epidermolysis bullosa gravis
      (JEBH) (Herlitz-type) (OMIM 226700). Screening for mutations of LAMB3 gene with
      polymerase chain reaction (PCR) amplification of all exons from genomic DNA and
      subsequent heteroduplex analysis and dideoxynucleotide sequencing of heteroduplex
      forming PCR products disclosed two mutations: the recurrent maternal mutation
      R635X and the novel paternal mutation 1629insG, both in exon 14 of LAMB3. Both
      mutations lead to a premature termination code, non-sense mediated mRNA decay and
      to absence of the synthesis of the beta3 chain of laminin 5. During the mutation
      screening of the index patient a second pregnancy was ascertained. After
      amniocentesis (14 + 1 week of pregnancy), prenatal diagnosis from fetal cells was
      performed and compound heterozygosity for both mutations was evident. The
      consultants decided to have a termination of pregnancy shortly after the
      diagnosis. Remarkable skin fragility of the fetus was evident by clinical
      examination. Complete absence of laminin 5 could be demonstrated by
      immunofluorescence staining. By the third pregnancy of this couple so far
      screened for mutations by chorionic villus sampling for prenatal molecular
      diagnosis a healthy but heterozygous child is expected.

PMID- 11451333
TI  - One-year treatment of chronic urticaria with mizolastine: efficacy and safety. J
      Eur Acad Dermatol Venereol 2000; 14: 83-90.

PMID- 11451334
TI  - Treatment of plantar erosive lichen planus with topical cyclosporin.

PMID- 11451335
TI  - Facial orf.

PMID- 11451336
TI  - Topical therapy with fluorinated and non-fluorinated corticosteroids in patients
      with atopic dermatitis.

PMID- 11451337
TI  - Acute paronychia: comparative treatment with topical antibiotic alone or in
      combination with corticosteroid.

PMID- 11451338
TI  - Keratosis lichenoides chronica.

PMID- 11451339
TI  - Longitudinal red streaks on the big toenails in a patient with pseudobulbar
      syndrome.

PMID- 11451340
TI  - Comparative effects of calcipotriol and betamethasone 17-valerate solution in the
      treatment of seborrhoeic dermatitis of the scalp.

PMID- 11451341
TI  - Tinea of the scalp and eyebrows caused by Trichophyton violaceum in a 62-year-old
      diabetic woman.

PMID- 11451342
TI  - Multiple squamous epitheliomas during long-term treatment with hydroxyurea.

PMID- 11451343
TI  - Familial occurrence of scleroderma.

PMID- 11451344
TI  - Epithelioid haemangioma (angiolymphoid hyperplasia with eosinophilia) in the
      inner canthus.

PMID- 11451345
TI  - Contact allergy to henna.

PMID- 11451346
TI  - Sex-Sorting mammalian sperm: concept to application in animals.
AB  - Sperm sexing can be used to produce sexed offspring with 85%-95% accuracy (Amann,
      1999; Johnson and Seidel, 1999; Seidel et al 1999a). On September 1, 2000, the
      sale of sexed bovine sperm commented in the United Kingdom. It will be
      interesting to see to what degree sexed sperm penetrate the semen market. This
      verified sexed product sets the stage for commercialization around the world in
      major animal producing countries. This commercialization of sexed sperm occurred
      nearly 20 years after technology for accurately determining the proportion of X
      and Y sperm in semen was first developed at Lawrence Livermore National
      Laboratory. It came about due to advances in both the hardware and the software
      componenets of computer science, biophysic, cell biology and applied reproductive
      physiology plus efforts of innovative scientist. Many individuals have
      contributed in making semen sexing in animals a commercial reality since the
      research team of Bart Gledhill, Dan Pinkel, Duane Garner, Susan Lake, and Larry
      Johnson began following up on the first flow cytometric studies on human sperm by
      Friedrich Otto, Wolfgang Gohde, and Marvin Meistrich. There was also major input
      from personnel at USDA Beltsville Agricultural Research Center as well as
      scientists at Cambridge University, Atlantic Breeders Cooperative, Colorado State
      University and XY Inc. These include Chuck Allen, Rupert Amann, David Cran,
      Patrick Doyle, Mike Evans, Lisa Herickhoff, Mervyn Jacobson, Kehuan Lu, Chris
      Polge, Wim Rens, John Schenk, George Seidel, Glenn Welch, and many others.

PMID- 11451347
TI  - Hox transcription factors may play a role in regulating segmental function of the
      adult epididymis.

PMID- 11451348
TI  - Making a production over reproductions.

PMID- 11451349
TI  - Understanding the odds ratio and the relative risk.
AB  - Both the odds ratio and the relative risk compare the relative likelihood of an
      event occurring between two groups. The relative risk is easier to interpret and
      is consistent with general intuition. Some designs, however, allow only for the
      calculation of the odds ration. Covariate adjustment is easier for an odds ratio.
      Finally, the odds ratio avoids ambiguity by being invariant to lthe labeling of
      the outcome measure. The Table summarizes the advantages and disadvantages of the
      odds ratio and relative risk. Whe reading research that summarizes data using
      odds ratios, or relative risks, be aware of the limitations of booth of these
      measures.

PMID- 11451350
TI  - Androgen receptor regulation of G1 cyclin and cyclin-dependent kinase function in
      the CWR22 human prostate cancer xenograft.
AB  - Human prostate cancer is initially dependent on androgens for growth, and
      androgen-dependent cells undergo apoptosis after castration. However, a subset of
      androgen-responsive cells survives and eventually proliferates in the absence of
      testicular androgen. The high levels of androgen receptor in both androgen
      dependent and recurrent tumors led us to investigate androgen regulation of cell
      cycle proteins in human prostate cancer using the CWR22 xenograft. Cellular
      proliferation decreased dramatically in CWR22 tumors after castration.
      Testosterone propionate (TP) treatment of castrated mice restored cellular
      proliferation after 24-48 hours. Growth of CWR22 tumors in the absence of
      testicular androgen recurred several months after castration. CDK1 and CDK2, and
      cyclin A and cyclin B1 messenger RNAs were decreased 6 days after castration,
      increased 6-12 hours after TP treatment, and were expressed at high levels in
      recurrent CWR22 tumors. Coimmunoprecipitated cyclin B1/CDK1 and cyclin D1/CDK4
      protein complexes decreased after castration and increased after TP treatment of
      castrated mice. In addition, CDK1 and CDK2 kinase activities were upregulated by
      androgen in parallel with hyperphosphorylation of retinoblastoma (Rb) protein.
      Despite the absence of testicular androgen in recurrent CWR22, the levels of
      these androgen-regulated cyclin/ CDK protein complexes and hyperphosphorylation
      of Rb were equal to or greater than in tumors from intact mice. The results
      indicate that androgen receptor regulates cellular proliferation by control of
      CDK and cyclins at the transcriptional level and by post-translational
      modifications that influence cell cycle protein activity.

PMID- 11451351
TI  - Mouse seminal vesicle secretory protein of 99 amino acids (MSVSP99):
      characterization and hormonal and developmental regulation.
AB  - Polyclonal antibodies have been generated to investigate the localization, tissue
      and species distribution, androgen regulation, and ontogeny of a protein secreted
      by mouse seminal vesicle, designated as MSVSP99 (ie, mouse seminal vesicle
      secretory protein of 99 amino acids). MSVSP99 is a polymorphic compound with a
      molecular weight of around 14 kilodaltons and a positive immunoreactivity range
      of 5.23 to 5.70. Positive immunoreactivity was restricted to the epithelial cells
      of the seminal vesicle. Western blot analysis showed organ specificity for
      MSVSP99, which could not be detected in several organs in the mouse. Time course
      decrease of MSVSP99 after castration closely followed that of its mRNA. In
      contrast, the length of time required to restore control levels after
      testosterone treatment was higher for the protein than it was for its mRNA.
      Whereas the MSVSP99 gene is already active in 10-day-old males, MSVSP99 is first
      detected at 27 days. Then, we conclude that factors other than the accumulation
      of the mRNA regulate MSVSP99 expression.

PMID- 11451352
TI  - Evaluation of flow cytometric methods to measure human sperm concentration.
AB  - Human sperm concentration is usually assessed using hemocytometry (HM). However,
      external and internal quality control schemes have shown that the accuracy of
      this method is low overall. Flow cytometry (FC) is a rapid, accurate, and
      reproducible technology for the quantification of various cell populations. We
      used 3 FC methods for human sperm counting from a 1:1 mixture of a diluted semen
      sample with a suspension of fluorospheres of known concentrations. The events
      that represented sperm cells were detected according to 1) gating on size and
      granularity (FCM1), 2) gating on DNA staining by propidium iodide (FCM2), and 3)
      a combination of FCM1 and FCM2 (FCM3). Sperm concentration was calculated from
      the ratio of detected events to fluorosphere counts and fluorosphere
      concentration. A pilot study undertaken by 12 technicians from different
      laboratories to compare FCM1 with HM showed a general agreement between both
      methods, despite wide variations in sperm concentration exhibited by HM due to
      the use of unoptimized procedures. A second experiment indicated that the overall
      variability in sperm concentration assessment by FCM1 was lower than that
      produced by HM when performed by 2 technicians using optimal procedures for 3
      preparations of the same semen samples. The overall mean coefficients of
      variation were 3.9% for FCM1 vs 8.0% for technician 1, 12.3% for technician 2 (P
      < .05), and 15.7% for both technicians (P < .05). FCM1, FCM2, and FCM3 were
      compared with HM performed by a single trained technician for 39 semen samples
      (triplicates) of various quality. Compared with HM, FCM1 and FCM2 overestimated
      the sperm concentration by 14% and 8%, respectively, against only 4% per million
      sperm for FCM3, which was effective for the full spectrum of sperm concentrations
      (except azoospermia). In conclusion, this study demonstrates that human sperm
      concentration can be accurately assessed by the FC method combining gating on
      cell size, granularity, and DNA staining.

PMID- 11451353
TI  - Quality control of reactive oxygen species measurement by luminol-dependent
      chemiluminescence assay.
AB  - A total of 28 donor semen samples were used to evaluate the characteristics of
      laboratory variability in measuring reactive oxygen species (ROS). The objectives
      of this study were to assess the interassay (same sample observed on different
      days by the same observers) variability; interdonor, intraobserver (replications
      of the same sample on the same day) variability; and interobserver (multiple
      observers on the same day with the same sample) variability of the luminol
      dependent chemiluminescence assay and to establish an optimal semen age and sperm
      concentration. Semen samples were collected from 6 healthy donors for 108
      measures of ROS. ROS levels were measured by the assay using luminol as the
      probe. An additional assessment measured the effect of time (age of the sample)
      on ROS production in 12 donor samples at 60, 120, 180, and 240 minutes after the
      specimen was produced. Last, to evaluate the effect of sperm concentration on ROS
      production, ROS levels were measured in 10 donor sample aliquots with sperm
      concentrations ranging from 1 to 120 x 10(6)/mL. In the controls, the mean ROS
      level was 0.218 x 10(6) counted photons per minute; the interassay variability
      standard deviation (SD) was 0.077. The interobserver SD was 0.002 for an
      interobserver reliability of 97.5% (coefficient of variation [CV] = 0.9%). The
      intraobserver (between replication) SD was 0.001 for an intraobserver reliability
      of 98.7% (CV = 0.5%). The interassay SD was 0.005 for an interassay reliability
      of 93.8% (CV = 2.0%). There was no statistically significant interobserver,
      intraobserver, or interassay variation (P > .80). ROS levels decreased
      significantly with time; a dramatic decline in ROS production was seen in the
      specimens that were more than 60 minutes old (P < .001). ROS values decreased by
      31% at 120 minutes and 62% at 180 minutes compared with the 60-minute-old
      specimens. A linear relationship was seen between the ROS levels and sperm
      concentration in 8 of the 10 samples analyzed (R2 = .99). Our results demonstrate
      that the luminol-dependent chemiluminescence assay for ROS measurement is both
      accurate and reliable when the sperm concentration is greater than 1 x 10(5)/mL
      and the samples are analyzed within the first hour after specimen collection.

PMID- 11451354
TI  - Relationship between seminal white blood cell counts and oxidative stress in men
      treated at an infertility clinic.
AB  - In semen, granulocytes are major producers of reactive oxygen species (ROS),
      which can damage sperm. The diagnosis of leukocytospermia is usually based on the
      World Health Organization (WHO) definition of 1 x 10(6) white blood cells per
      milliliter, but controversy remains over the minimum leukocyte level that impairs
      fertility. The goals of this study were to clarity the relationship between
      leukocyte count and oxidative stress and to establish the minimum leukocyte count
      associated with oxidative stress. To do so, we compared oxidative stress in semen
      samples with different leukocyte counts (by the Endtz test) after a simple wash
      and-resuspend procedure and determined the correlation between leukocyte counts
      and oxidative stress (expressed as ROS-TAC score, a composite score calculated
      from ROS levels and total antioxidant capacity (TAC), both measured with
      chemiluminescence assays). ROS-TAC decreases as oxidative stress rises. We
      compared specimens from 271 men attending an infertility clinic and 28 healthy
      controls. About 9% of patients had WHO-defined leukocytospermia and an additional
      16% had some leukocytes. Samples with no seminal leukocytes had significantly
      lower ROS levels and significantly higher ROS-TAC scores than samples with any
      seminal leukocytes, even very low levels. Oxidative stress was correlated with
      rising white blood cell (WBC) count (r = .39; P < .001). Receiver operating
      characteristics curves showed that ROS-TAC score would be fairly accurate at
      distinguishing between patients with any leukocytes and those with no leukocytes
      (area under the curve, 75%). In conclusion, oxidative stress occurs even in
      patients with very low seminal WBC counts (between 0 and 1 x 10(6)/mL) and rises
      with an increase in WBC count. Therefore, we are unable to determine a safe
      minimum WBC count; the presence of any WBCs is associated with oxidative stress
      and may therefore impair fertility. Complete removal of WBCs from semen samples
      used for assisted reproduction may help reduce oxidative stress.

PMID- 11451355
TI  - Measurement of bovine sperm nuclear shape using Fourier harmonic amplitudes.
AB  - An objective method for measuring bovine sperm nuclear shape was developed.
      Digital images of bovine sperm stained with propidium iodide were collected and
      Fourier functions used to describe the perimeters of individual sperm nuclei.
      Harmonic amplitudes from Fourier functions were first shown to be independent of
      sperm orientation during digitization. Sperm from 12 different bulls were used,
      and 6 harmonic amplitudes per sperm were found to adequately describe sperm
      nuclear shape. Based on harmonic amplitudes 0 to 5, cluster analysis was used to
      generate 20 different groups. Sperm within groups had similar morphologies and
      groups were distinguished by statistically unique shape characteristics. Harmonic
      amplitudes 0 to 5 can be used to distinguish previously reported abnormalities
      such as tapered, pyriform, macrocephalic, and microcephalic, as well as
      gradations in between. Furthermore, differences were detected among bull harmonic
      amplitude centroids (P < .05), indicating that bulls differ in mean sperm nuclear
      shape.

PMID- 11451356
TI  - Relationship of bull fertility to sperm nuclear shape.
AB  - The relationship between sperm nuclear shape and bull fertility was determined.
      Two groups of bulls, 3 per group, were selected. Bulls differed in fertility
      based on lifetime nonreturn rates. Digital images of propidium iodide-stained
      sperm from each bull were collected and shape-evaluated by Fourier harmonic
      amplitudes 0 to 5. A discriminant function (P < .05) was constructed based on
      harmonic amplitudes and the 2 fertility groups. When individual sperm were
      classified as being of high or lower fertility, the percentage of each bull's
      sperm placed in the high-fertility group had a linear relationship (r = .89, P <
      .05) with fertility. To construct a plot of mean sperm shapes, a novel technique
      to automatically orient and identify the anterior tip of the sperm head was
      developed. The mean nuclear shape of high-fertility sperm was more elongated and
      tapered than those of lower fertility. A discriminant function (P < .05) was also
      constructed that separated the 6 bulls into 2 groups based only on the harmonic
      amplitudes or sperm nuclear shape. The bulls were correctly classified into the 2
      fertility groups. A comparison of sperm chromatin structure analysis (SCSA) and
      harmonic amplitudes found that overall size variance, anterior roundness, and
      posterior taperedness of sperm nuclei were related to chromatin stability (P <
      .05). Some of the differences observed in sperm nuclear shape between the high-
      and lower-fertility bulls may be explained by varying levels of chromatin
      stability. However, sperm nuclear shape appears to contain additional information
      from chromatin stability alone. In this particular study, with 6 bulls, all with
      good chromatin quality, sperm nuclear shape was a better predictor of bull
      fertility.

PMID- 11451357
TI  - Altered protamine 2 expression is uncommon in donors of known fertility, but
      common among men with poor fertilizing capacity, and may reflect other
      abnormalities of spermiogenesis.
AB  - During the spermatid elongation stage of spermiogenesis approximately 85% of
      sperm nuclear histones are replaced by protamines. Protamines increase the
      packing ratio of sperm chromatin, presumably facilitating sperm motility and
      function. In this study we evaluated the incidence of abnormal protamine
      expression in 75 patients undergoing in vitro fertilization (IVF) and 50 donors
      of known fertility by isolation of sperm nuclear proteins, quantitative gel
      electrophoresis, and Western blot analysis. In addition, we evaluated the
      relationship between abnormal protamine expression and semen quality, sperm
      penetration ability, chromatin stability, and IVF outcome. Seventeen percent
      (13/75) of IVF patients had no measurable protamine 2 (P2) versus 0% (0/50) of
      donors of known fertility (P < .005). Sperm penetration rates were decreased in
      12 of 13 patients without P2, and mean penetration rates (4.6 +/- 1.2 vs 32.8 +/-
      2.9, P < .005), normal morphology (22.4 +/- 3.6 vs 48.7 +/- 4.2, P < .05), and
      progressive motility (22.3 +/- 2.5 vs 35.4 +/- 2.1, P < .05) were all
      significantly decreased compared with patients with measurable P2. The mean sperm
      concentration was not significantly different. The presence of protamine
      precursor bands was also associated with a diminished penetration capacity (18.4
      +/- 2.8 vs 36.7 +/- 3.0, P < .05). Sperm chromatin decondensation following
      exposure to heparin sulfate was significantly increased in patients without a
      measurable P2 band. Twelve patients with no measurable P2 underwent
      intracytoplasmic sperm injection (ICSI), with 6 patients (6/12, 50%) becoming
      pregnant. ICSI fertilization and subsequent embryo cleavage were not different in
      patients without P2 compared with other patients undergoing ICSI. These data
      indicate that abnormal sperm protamine levels are a common defect in infertility
      patients, but not in donors of known fertility. It appears that abnormal
      protamine levels may reflect defects of late spermiogenesis, including sperm
      penetration capacity.

PMID- 11451358
TI  - A redox-regulated tyrosine phosphorylation cascade in rat spermatozoa.
AB  - Rat spermatozoa from both the caput and cauda epididymidis were shown to generate
      superoxide anion (O2-.) both spontaneously and following stimulation with
      NAD(P)H. Caput spermatozoa gave a significantly greater O2- response to NADPH
      stimulation than caudal cells, whereas in both cell types the responses to
      exogenous NADPH and NADH were approximately equivalent. Analysis of H2O2
      production revealed that this oxidant was generated only by caudal epididymal
      cells and only in these cells did the stimulation of reactive oxygen species
      (ROS) production with NADPH lead to an increase in tyrosine phosphorylation.
      Stimulation of ROS production with NADPH increased intracellular cyclic adenosine
      monophosphate (cAMP) levels in both caput and caudal epididymal cells, but only
      in caudal cells did cAMP stimulate tyrosine phosphorylation, in keeping with the
      NADPH results. On the basis of these findings we propose that tyrosine
      phosphorylation in rat spermatozoa is driven by ROS acting via 2 different but
      complementary mechanisms; O2-. stimulates tyrosine kinase activity indirectly
      through the elevation of intracellular cAMP while H2O2 acts directly on the
      kinase/phosphatase system, stimulating the former and inhibiting the latter. Zinc
      was examined as a potential regulator of this signal transduction cascade and was
      shown to suppress tyrosine phosphorylation in caput cells but to promote this
      activity in caudal spermatozoa, possibly through an inhibitory effect on tyrosine
      phosphatase activity. These results reveal the maturation of a redox-regulated,
      cAMP-mediated, signal transduction cascade during epididymal transit in the rat
      that is sensitive to zinc and plays a key role in the control of tyrosine
      phosphorylation events associated with capacitation.

PMID- 11451359
TI  - Intracavernosal sildenafil facilitates penile erection independent of the nitric
      oxide pathway.
AB  - Sildenafil, in nanomolar serum levels, is an effective phosphodiesterase type 5
      inhibitor, and facilitates penile erection only during sexual stimulation.
      However, there is limited information on the pharmacological activity of this
      agent when tissue levels approach millimolar concentrations following
      intracavernosal injection. The aim of this study was to investigate whether
      sildenafil causes penile erection in the absence of active neurogenic input.
      Organ bath preparations of rabbit penile cavernosal tissue strips were contracted
      with 1 microM phenylephrine and exposed to increasing concentrations of
      sildenafil in the absence or presence of the nitric oxide (NO) synthase
      inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME; 0.6 mM). Sildenafil
      caused dose-dependent relaxation of rabbit cavernosal smooth muscle at high
      concentrations (>0.1 microM) with little or no effect at concentrations below 0.1
      microM. The addition of L-NAME did not affect this response. In a separate
      protocol, sildenafil dose response determinations were performed in the presence
      of the guanylyl cyclase inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one
      (ODQ; 3 microM) or vehicle (50% dimethyl sulfoxide [DMSO]). Relaxation to
      sildenafil in the presence of DMSO was significantly enhanced relative to
      sildenafil alone. ODQ treatment partially attenuated relaxation to sildenafil,
      but failed to completely inhibit the response. In cavernosal tissue strips,
      sildenafil elevated basal cyclic guanosine monophosphate (cGMP) levels twofold
      (0.54 vs. 1.10 pmol/mg prot). To further investigate these observations,
      anesthetized rabbits were injected intracavernosally with sildenafil (0.3-1.3
      mg). In the absence of pelvic nerve stimulation, the magnitude and duration of
      the intracavernosal pressure increased in a dose-dependent fashion in response to
      sildenafil, approaching the systemic arterial pressure at higher doses.
      Intracavernosal administration of L-NAME, at doses that inhibited pelvic nerve
      stimulated penile erection, did not alter the response to intracavernosal
      sildenafil at 1.3 mg. Sildenafil, at the doses tested, did not significantly
      change the systemic arterial pressure. These data suggest that intracavernosal
      sildenafil, at tissue levels approaching millimolar concentrations, can cause
      relaxation of vascular smooth muscle and penile erection by a novel mechanism
      independent of the classical NO/cGMP pathway.

PMID- 11451360
TI  - E2F and GATA-1 are required for the Sertoli cell-specific promoter activity of
      the follicle-stimulating hormone receptor gene.
AB  - The follicle-stimulating hormone receptor (FSHR) gene is expressed in Sertoli
      cells in males and in granulosa cells in females. Cis-acting sequences and
      associated binding factors responsible for the transcription of the TATA-less
      FSHR gene in Sertoli cells were analyzed with dimethylsulfate (DMS) footprinting
      assays and electrophoretic mobility shift assay (EMSA). In vivo footprints in the
      core promoter using nuclear proteins from Sertoli cells identified several
      protected sequences, including an inverted GATA (TATC, -88/-85), and an E2F
      (TTTCGCG, -45/-39) motif. EMSA showed the presence of one or more sequence
      specific proteins interacting with these potential regulatory elements. Antibody
      supershift assays as well as competition assays further revealed that testis
      specific GATA-1 recognized the inverted GATA element. The functional role of the
      potential cis-acting elements was analyzed by transient transfection assays with
      and without mutations of the putative elements. The mutational analysis indicated
      that the GATA and E2F elements were each required for optimal promoter activity.
      The effects of each of the promoter elements was examined in transfections in
      which mutations were made in each of the known regulatory sites, including the E
      box, GATA, and E2F sites in various combinations. All of these sites contribute
      to the maximum promoter activity such that mutations of the E box, GATA, and E2F
      sites eliminated nearly all promoter activity.

PMID- 11451361
TI  - Assessment of the androgen environment within the human testis: minimally
      invasive method to obtain intratesticular fluid.
AB  - Previous studies of the rat have shown that testosterone concentrations within
      the interstitial and seminiferous tubularfluids of the testes are significantly
      higher than normal serum levels, and further, that although intratesticular
      testosterone concentration can be substantially reduced without an effect on
      spermatogenesis, the concentration that is minimally required to maintain
      spermatogenesis is also substantially higher than serum levels. The purpose of
      the present study was to adapt a minimally invasive technique to sample human
      intratesticular fluid to enable parallel observations in man. To this end,
      aspiration methods were first developed for the rat testis and then adapted to
      the human. The testosterone concentration in fluid obtained by unilateral
      aspiration of rat testes was approximately 50 ng/mL, similar to the known
      concentration in seminiferous tubular fluid. These aspiration methods were then
      adapted to obtain intratesticular fluid from human testes. Studies of 12 fertile
      human subjects demonstrated that percutaneous testicular aspiration could be
      performed safely and successfully using a 19-gauge needle. Nine additional human
      subjects had bilateral testicular aspiration and simultaneous measurement of
      peripheral blood testosterone levels. Testicular aspirations yielded 8 to 117
      microL of fluid from each testicle. The mean concentration of testosterone in
      aspirates obtained from the 21 patients was 609 +/- 50 ng/mL. Dihydrotestosterone
      and 3alpha-androstanediol concentrations were quite low, below the limits of
      detection of our assay. The SHBG/ABP concentration in the aspirates was 8.5 +/-
      1.1 nM. These results define testosterone as the major androgenic steroid in the
      human testis, as in the rat testis, and indicate that the testosterone
      concentration within the human testis is approximately 200-fold greater than that
      of SHBG/ABP, and more than 100-fold greater than the concentration of
      testosterone found in normal human serum.

PMID- 11451362
TI  - Cryopreservation-Thawing of fractionated human spermatozoa is associated with
      membrane phosphatidylserine externalization and not DNA fragmentation.
AB  - The objective of these studies was to evaluate the effect of cryopreservation
      thawing of human spermatozoa on DNA fragmentation and membrane integrity. This
      was a prospective, controlled cohort study, performed at a university-based
      infertility center. Ejaculates were examined from 5 donors and 16 men undergoing
      infertility evaluation. Purified sperm populations were prepared by gradient
      centrifugation, cryopreserved using a manual method and TEST-yolk buffer and
      glycerol (TYB-G), followed by quick-thaw. Annexin V binding was used for
      assessing membrane translocation of phosphatidylserine, and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was utilized
      for the evaluation of DNA fragmentation. The results were as follows: the
      percentage of live cells with intact membranes (annexin V-, live) was
      significantly reduced after cryopreservation-thawing. On the other hand, the
      percentages of live cells with phosphatidylserine translocation (annexin V-,
      live) and of necrotic (dead) cells increased significantly after thawing. TUNEL
      revealed percentages of cells with DNA fragmentation in the prefreeze and
      postthaw samples that were not significantly different. In a further attempt to
      examine differences in response to various cryoprotection protocols, experiments
      were carried out using no cryoprotection, glycerol alone, or TYB-G. Samples
      frozen with TYB-G demonstrated significantly higher percentages of live cells
      without phosphatidylserine translocation than the other conditions. We concluded
      that cryopreservation-thawing of human sperm from patients and donors was
      associated with membrane change, as revealed by membrane translocation of
      phosphatidylserine, while having no major impact on DNA fragmentation.

PMID- 11451363
TI  - Immortalized testis cell lines from estrogen receptor (ER) alpha knock-out and
      wild-type mice expressing functional ERalpha or ERbeta.
AB  - The surprising findings that male mice lacking the estrogen receptor (ER) alpha
      (alphaERKO) have atrophic testis and are infertile proved that ERalpha is
      involved in normal testicular function. To obtain compatible in vitro model
      systems for alphaERKO male mice, we immortalized different cell lines from the
      testis of alphaERKO and wild-type (C57BL/6) mice with the human papilloma virus
      E6/E7 genes. The established cell lines were characterized for Sertoli, Leydig,
      and peritubular cell markers by means of messenger RNA expression and functional
      assays. One wild-type-derived cell line showed Leydig cell-specific marker gene
      expression and produced testosterone after stimulation with cyclic adenosine
      monophosphate. Most wild-type cell lines expressed androgen receptor and a
      functional ERalpha as shown by high estrogenic activity in a luciferase-based
      transactivation assay. Most notably, the wild-type-derived WL3, and the ES4 cell
      line derived from alphaERKO mice expressed ERbeta and showed ER-mediated
      transcriptional activity, but no ERalpha protein expression. These cell lines
      with and without functional ERalpha or ERbeta enable the analyses of ER subtype
      specific responses and their function in testicular cell signaling,
      morphogenesis, and neoplasia.

PMID- 11451364
TI  - Purification of rat leydig cells: increased yields after unit-gravity
      sedimentation of collagenase-dispersed interstitial cells.
AB  - Procedures for purification of Leydig cells have facilitated studies of their
      regulatory biology. A multistep procedure that includes a filtration with nylon
      mesh (100-micron pore size) to separate interstitial cells from the seminiferous
      tubules, combining centrifugal elutriation and Percoll density gradient
      sedimentation, has been used to obtain a 95% enrichment of rat Leydig cells.
      However, the number of recovered Leydig cells by this procedure represents only a
      small fraction of the 25 million, on average, that exist in the adult rat testis.
      The objective of this study was to test whether the yield of purified Leydig
      cells might be enhanced by substitution of unit-gravity sedimentation (S method)
      for the filter step (F method). We also asked whether a greater number of Leydig
      cell clusters, macrophages, or both would be recovered by this new method, and if
      the presence of Leydig cell clusters is associated with increased capacity for
      testosterone production in vitro. The number of purified Leydig cells was 1.9
      fold higher for the S method than for the F method, with no differences in purity
      assessed by 3beta-hydroxysteroid dehydrogenase histochemical staining. Leydig
      cell clusters were also found in greater numbers with the S method both after
      collagenase dispersion and at the end of the purification. No differences were
      seen in testosterone production or in the number of macrophages present in the
      Leydig cells that were prepared by the 2 methods. These results indicate that the
      new method recovers greater numbers of Leydig cells by collecting clustered
      Leydig cells that are systematically eliminated when a filtration step is used.

PMID- 11451365
TI  - Semenogelin, the main protein of semen coagulum, inhibits human sperm
      capacitation by interfering with the superoxide anion generated during this
      process.
AB  - Semenogelin (Sg), the major protein of the human semen coagulum, is present at
      high concentrations in seminal vesicle secretions. It is degraded by the prostate
      specific antigen (PSA) to generate peptides of various biological activities that
      were found on and inside spermatozoa. Our aim was to determine the effect of Sg
      on capacitation, which is the series of transformations that spermatozoa must
      undergo to become fertile. At concentrations of 0.1 to 1.0 mg/mL (600- to 20-fold
      lower than those of semen), Sg did not affect sperm motility (%) but completely
      prevented capacitation induced by fetal cord serum ultrafiltrate; a partial
      inhibition of capacitation was noted with 0.03 mg Sg/mL. There was also a dose
      dependent decrease in the tyrosine phosphorylation of fibrous sheath proteins and
      in the O2-.-related chemiluminescence. Ribonuclease (RNase), which has as high an
      isoelectric point (pI = 9.7) as Sg (pI = 9.5), also prevented sperm capacitation
      and O2-.-related chemiluminescence but to a lower extent, suggesting that one
      mechanism of Sg action on spermatozoa could be related to its positive charge at
      physiological pH. Sg at 1, but not 0.3 or 0.1 mg/mL, scavenged the O2-. generated
      by the mix of xanthine + xanthine oxidase and modified the kinetics of the
      reaction; RNase did not have such effects. Therefore, Sg is a potential scavenger
      for O2-. but probably also affects the sperm oxidase. Spermatozoa rapidly
      processed Sg; a high proportion of Sg was degraded after 15 minutes of
      incubation. The resulting polypeptide patterns were reminiscent of those obtained
      with PSA as a proteolytic enzyme. These data suggest that Sg, its degradation
      products, or both may be natural regulators of sperm capacitation and could
      prevent this process from occurring prematurely. One mechanism by which Sg acts
      could involve an interference with the O2-. that is normally generated during
      this process.

PMID- 11451366
TI  - The role of glucose in supporting motility and capacitation in human spermatozoa.
AB  - Glucose has been reported to be beneficial to human sperm for optimal
      capacitation and fertilization, although it is unclear whether glucose is
      required for providing extra metabolic energy through glycolysis, or for
      generating some other metabolic product. In this study, the effects of sugars on
      human sperm capacitation, motility, and energy production were investigated. The
      glucose concentration that supported the greatest number of acrosome reactions
      was 5.56 mmol L(-1). Compared with incubations with no added sugar, this
      concentration of glucose, fructose, mannose, or galactose appeared to slightly
      increase the number of acrosome reactions occurring after 18 hours of
      capacitation, or following induction by 2 micromol A23187 + 3.6 mmol
      pentoxifylline L 1, but only glucose had a statistically significant effect.
      Glucose supported increased penetration of zona-free hamster oocytes, but its
      advantage was not statistically significant. The addition of 5.56 mmol glucose or
      fructose L(-1) to sugar-free medium immediately increased the adenosine
      triphosphate (ATP) concentration and motility of sperm. These parameters were
      then stable for 3 hours, but declined markedly after 18 hours. In the absence of
      a glycolysable sugar, motility began to decline in the first hour and only 2% or
      3% of sperm remained motile after 18 hours. Glucose or fructose was required to
      support hyperactivated motility. 2-Deoxyglucose was detrimental to the ATP
      concentration and motility of sperm, and supported fewer spontaneous or
      progesterone-stimulated acrosome reactions than were observed in the absence of a
      sugar. We conclude that glycolytic ATP production is required for vigorous
      motility and hyperactivation in human sperm. Other products of glucose metabolism
      are not essential to support capacitation, but they may have a small, enhancing
      effect.

PMID- 11451367
TI  - Immunomagnetic isolation and long-term culture of mouse type A spermatogonia.
AB  - In the mammalian testis, type A spermatogonia proliferate and differentiate into
      sperm under the tight control of both endocrine and paracrine factors. In order
      to study the complex process of spermatogenesis at the molecular level, an in
      vitro system must be devised in which type A spermatogonia can be cultured for a
      prolonged period of time. Therefore, cocultures including type A spermatogonia
      and Sertoli cells, which act as nurse cells to the developing germ cells, are
      desirable. We have developed a method for the specific isolation of type A
      spermatogonia using magnetic beads and antibodies that recognize the c-kit
      receptor or the homophilic adhesion molecule, Ep-CAM. Purified spermatogonia
      could survive for a period of 25 days when cocultivated on Sertoli cell
      monolayers. Moreover, we recently established Sertoli cell lines that produce
      growth factors that are essential for the maintenance of spermatogonia in a
      proliferative state. Some of these Sertoli cell lines are able to reorganize into
      tubular structures when cultivated on a layer of Matrigel as extracellular
      matrix. We show here that type A spermatogonia associate specifically with the
      Sertoli cell tubules, and are able to replicate their DNA in this environment.
      Thus, these in vitro culture systems could be used for the long-term culture of
      primary, nonimmortalized type A spermatogonia.

PMID- 11451368
TI  - The SMRT corepressor is a target of phosphorylation by protein kinase CK2 (casein
      kinase II).
AB  - The Silencing-Mediator for Retinoid/Thyroid hormone receptors (SMRT) interacts
      with, and mediates transcriptional repression by, a variety of eukaryotic
      transcription factors, including the nuclear hormone receptors. The ability of
      SMRT to function as a transcriptional 'corepressor' is regulated by a variety of
      signal transduction pathways. We report here that SMRT is a phosphoprotein in
      vivo, and is also phosphorylated in vitro by unfractionated cell extracts. A
      major site of phosphorylation of SMRT is a protein kinase CK2 motif centered on
      serine 1492, and located within a C-terminal SMRT domain that mediates
      interaction of the corepressor with the nuclear hormone receptors.
      Phosphorylation of SMRT by CK2 stabilizes the ability of the SMRT protein to
      interact with nuclear hormone receptors. Our results indicate that SMRT is a
      member of an expanding family of transcriptional regulators that are modified,
      and potentially regulated, in response to protein kinase CK2.

PMID- 11451369
TI  - Differential inhibition of recombinant bovine GH (rbGH) activity in vitro by in
      vivo enhancing monoclonal antibodies.
AB  - We have previously described the effects of complexing recombinant bovine growth
      hormone (rbGH) with the in vivo enhancing monoclonal antibodies (Mabs) OA11 and
      OA15 and the non-enhancing Mab OA14 on the subsequent activity of GH in different
      tissue culture models. We reported that all of these Mabs caused the inhibition
      of GH-stimulated Jak-2 tyrosine kinase phosphorylation in the GH responsive pre
      adipocyte cell line 3T3-F442A. However, using the mouse myeloid cell line FDC-P1
      transfected with the full length ovine GH receptor (GHR), we subsequently found
      that OA11 and OA14 remained inhibitory with respect to the end point measurement
      of GH stimulated mitogenesis but that OA15 had no inhibitory effect on GH
      stimulated mitogenesis in this cell line. In order to correlate longer term
      mitogenic effects of Mab-GH complexes with signalling events in this transfected
      cell line model, we now report on the effects of complexing with Mab on the
      subsequent GH stimulated phosphorylation of Stat5b (signal transducer and
      activator of transcription). In agreement with our data for the mitogenic
      activity of GH-Mab complexes, we found that OA11 and OA14 inhibit GH activation
      of Stat5b but that OA15 is not inhibitory. Further to this, the dose-response
      effect of both OA11 and OA14 on the GH stimulation of Stat5b in the FDC-P1-oGHR
      transfected cells correlates with the previously described dose-response effects
      for both Mabs in the context of GH stimulation of mitogenic effects. We conclude
      that in this oGHR transfected cell line model, Mab effects on short and long term
      GH signalling events are tightly correlated. The observation that neither of the
      in vivo enhancing Mabs--OA11 or OA15--amplifies the response to GH in our
      transfected cell line model, coupled with the differential nature of Mab effects
      on GH activity (OA11--inhibition; OA15--no effect) may argue for an in vivo
      mechanism for enhancement of GH activity.

PMID- 11451370
TI  - A unique surface membrane anchored purine-salvage enzyme is conserved among a
      group of primitive eukaryotic human pathogens.
AB  - Previously, we isolated and characterized the gene encoding the 3'
      Nucleotidase/Nuclease (Ld3'NT/NU) from the human pathogen, Leishmania donovani.
      This unique cell surface enzyme has been shown to be involved in the salvage of
      host-derived purines, which are essential for the survival of this important
      protozoan parasite. In this report, we assessed whether the 3'
      Nucleotidase/Nuclease was conserved amongst other pathogenic Leishmania and
      related trypanosomatid parasites. Results of pulsed field gel electrophoresis and
      Southern blotting showed that a Ld3'NT/NU gene homolog was present in each of the
      visceral and cutaneous Leishmania species tested (i.e. isolates of L. donovani,
      L. infantum, L. tropica, L. major and L. mexicana, respectively). Further,
      results of colorimetric assays using 3'-adenosine monophosphate as substrate
      demonstrated that each of these organisms also expressed significant levels of 3'
      nucleotidase enzyme activity. In addition, we showed that a Ld3'NT/NU gene
      homolog was expressed in each of these Leishmania species as a > 40 kDa 3'
      nucleotidase enzyme activity. A Ld3'NT/NU gene homolog was also identified in two
      Crithidia species (C. fasciculata and C. luciliae) and Leptomonas seymouri but
      was only marginally detectable in Trypanosoma brucei, Trypanosoma cruzi and
      Phytomonas serpens. Cumulatively, results of this study showed that an Ld3'NT/NU
      homolog was conserved amongst pathogenic Leishmania sp. which suggests that this
      enzyme must play an critical role in purine salvage for all members of this group
      of human pathogens.

PMID- 11451371
TI  - Survey of normal appearing mouse strain which lacks malic enzyme and Nad+-linked
      glycerol phosphate dehydrogenase: normal pancreatic beta cell function, but
      abnormal metabolite pattern in skeletal muscle.
AB  - We studied a mouse doubly homozygous for mutations in the genes encoding malic
      enzyme (EC 1.1.1.40) and cytosolic glycerol phosphate dehydrogenase (EC 1.1.1.8)
      (cGPD). This mouse, which we call the mmgg mouse and which is the product of
      intercrosses between the Mod-1 mouse and the BALB/cHeA mouse, lacks activity of
      both enzymes. Like both parental strains the mmgg mouse is completely normal in
      appearance. cGPD is one of the two enzymes that catalyze the reactions of the
      glycerol phosphate shuttle. The activity of the other enzyme of the glycerol
      phosphate shuttle, mitochondrial glycerol phosphate dehydrogenase (EC 1.1.99.5)
      (mGPD), is abundant in tissues, such as brain, skeletal muscle and the pancreatic
      islet, suggesting that the glycerol phosphate shuttle is important in these
      tissues which rapidly metabolize glucose. Cytosolic malic enzyme activity is
      important for shuttles which transport NADPH equivalents from mitochondria to the
      cytosol. The major finding of the study was a highly abnormal metabolite pattern
      in tissues of the mmgg mouse suggesting a block in the glycerol phosphate shuttle
      due to cGPD deficiency. The metabolite pattern did not suggest that malic enzyme
      deficiency caused an abnormality. Tissue levels of glycerol phosphate (low) and
      dihydroxyacetone phosphate (high) were only abnormal in skeletal muscle.
      Glycolytic intermediates, situated at or before the triose phosphates in the
      pathway, such as fructose bisphosphate and glyceraldehyde phosphate were
      increased depending on the tissue. Taken together with previous extensive data on
      the mouse deficient only in cGPD, this suggests a block in glycolysis at the step
      catalyzed by glyceraldehyde phosphate dehydrogenase caused by an abnormally low
      NAD/NADH ratio resulting from a nonfunctional glycerol phosphate shuttle.
      Consistent with this idea the lactate/pyruvate ratio was high in skeletal muscle
      signifying a low cytosolic NAD/NADH ratio. The mmgg mouse was normal in all other
      factors studied including blood glucose and serum insulin levels, pancreatic
      islet mass, insulin release from isolated pancreatic islets, as well as the
      activities of five metabolic enzymes, including mGPD, in liver, kidney, skeletal
      muscle and pancreatic islets. cGPD enzyme activity was undetectable in pancreatic
      islets, 0.5% of normal in liver, and 2.1% of normal in kidney and skeletal
      muscle. Malic enzyme activity was undetectable in these same tissues.

PMID- 11451372
TI  - Substituted hydrophobic and hydrophilic residues at methionine-68 influence the
      chaperone-like function of alphaB-crystallin.
AB  - Amino acid residues 57-69 in alphaB-crystallin have been implicated as a target
      protein binding site. Moreover, a direct correlation between the extent of alpha
      crystallin hydrophobicity and chaperone-like activity has been demonstrated. The
      purpose of this study was to mutate a moderately hydrophobic residue Met-68 (M
      68) in the above region to strongly hydrophobic and hydrophilic residues and show
      whether chaperoning ability is affected with or without structural changes.
      Mutation of M-68 to Val, Ile or Thr did not result in significant changes in
      molecular mass and secondary and tertiary structures. However, the Val and Ile
      mutants showed significant improvement and the Thr mutant showed substantial loss
      in chaperone activity. Differences in chaperone function in the absence of any
      structural changes confirmed that the hydrophobicity or hydrophilicity of the
      substituted amino acid in the putative target protein binding site was the only
      contributing factor.

PMID- 11451373
TI  - Restoration of Ca2+-inhibited oxidative phosphorylation in cardiac mitochondria
      by mitochondrial Ca2+ unloading.
AB  - Mitochondria, the major source of cellular ATP, display high vulnerability to
      metabolic stress, in particular to excessive Ca2+ loading. Here, we show that
      Ca2+-inhibited mitochondrial ATP generation could be restored through stimulated
      Ca2+ discharge from mitochondrial matrix. This was demonstrated using a Ca2+
      ionophore or through Na+/Ca2+ exchange-mediated decrease of mitochondrial Ca2+
      load. Furthermore, diazoxide, a mitochondrial potassium channel opener, which
      maintained mitochondrial Ca2+ homeostasis, also restored Ca2+-inhibited ATP
      synthesis and preserved the structural integrity of Ca2+-challenged mitochondria.
      Thus, under conditions of excessive mitochondrial Ca2+ overload targeting
      mitochondrial Ca2+ transport pathways restores oxidative phosphorylation required
      for vital cellular processes. This study, therefore, identifies an effective
      strategy capable to rescue Ca2+-disrupted mitochondrial energetics.

PMID- 11451374
TI  - Schisandrin B modulates the ischemia-reperfusion induced changes in non-enzymatic
      antioxidant levels in isolated-perfused rat hearts.
AB  - Isolated Langendorff-perfused rat hearts were subjected to a fixed period of
      ischemia followed by increasing periods of reperfusion for investigating the
      changes in the extent of ischemia-reperfusion (IR) injury and tissue levels of
      non-enzymatic antioxidants. Effects of schisandrin B (Sch B) and (+/-) alpha
      lipoic acid (LA) pretreatment were also examined. A 40-min of ischemia (40-I)
      followed by 20- or 40-min of reperfusion (20-R or 40-R) caused sustainable tissue
      damage in isolated hearts, as indicated by the increased extent of lactate
      dehydrogenase (LDH) leakage and impaired contractile force. The myocardial IR
      injury was associated with a marked decrease in tissue ascorbic acid (V(C))
      level. However, myocardial reduced glutathione (GSH) and alpha-tocopherol (V(E))
      levels remained relatively unchanged except under a more severe IR condition (40
      I, 40-R). Pretreating rats with Sch B or LA at a daily dose of 1.2 mmol/kg for 3
      days protected against IR injury in isolated hearts to varying degrees. While
      only Sch B pretreatment could improve the recovery of contractile force, LA
      pretreatment produced a better inhibitory effect on LDH leakage. The protection
      against IR injury was associated with significant increases in myocardial V(E)
      and V(C) levels in both Sch B and LA pretreated hearts. The ensemble of results
      suggests that the cardioprotection afforded by Sch B or LA pretreatment may at
      least in part be attributed to the modulation on the interplay among non
      enzymatic antioxidants under oxidative stress induced by IR.

PMID- 11451375
TI  - Macrocompartmentation of total creatine in cardiomyocytes revisited.
AB  - Distribution of total creatine (free creatine + phosphocreatine) between two
      subcellular macrocompartments--mitochondrial matrix space and cytoplasm--in heart
      and skeletal muscle cells was reinvestigated by using a permeabilized cell
      technique. Isolated cardiomyocytes were treated with saponin (50 microg/ml for 30
      min or 600 microg/ml for 1 min) to open the outer cellular membrane and release
      the metabolites from cytoplasm (cytoplasmic fraction, CF). All mitochondrial
      population in permeabilized cells remained intact: the outer membrane was
      impermeable for exogenous cytochrome c, the acceptor control index of respiration
      exceeded 10, the mitochondrial creatine kinase reaction was fully coupled to the
      adenine nucleotide translocator. Metabolites were released from mitochondrial
      fraction (MF) by 2-5% Triton X100. Total cellular pool of free creatine +
      phosphocreatine (69.6 +/- 2.1 nmoles per mg of protein) was found exclusively in
      CF and was practically absent in MF. When fibers were prepared from perfused rat
      hearts, cellular distribution of creatine was not dependent on functional state
      of the heart and only slightly modified by ischemia. It is concluded that there
      is no stable pool of creatine or phosphocreatine in the mitochondrial matrix in
      the intact muscle cells, and the total creatine pool is localized in only one
      macrocompartment--cytoplasm.

PMID- 11451376
TI  - Enhanced activity and level of protein kinase A in the spinal cord supernatant of
      diisopropyl phosphorofluoridate (DFP)-treated hens. Distribution of protein
      kinases and phosphatases in spinal cord subcellular fractions.
AB  - Diisopropyl phosphorofluoridate (DFP) is a type I organophosphorus compound and
      produces delayed neurotoxicity (OPIDN) in adult hens. A single dose of DFP (1.7
      mg/kg, s.c.) produces mild ataxia in hens in 7-14 days, which develops into
      severe ataxia or paralysis as the disease progresses. We have previously shown
      altered expression of several proteins (e.g. Ca2+/calmodulin-dependent protein
      kinase II (CaM kinase II) alpha-subunit, tau, tubulin, neurofilament protein
      (NF), vimentin, GFAP) and an immediate early gene (e.g. c-fos) in DFP-treated
      hens. Here we show an increase in protein kinase A (PKA) protein level and
      activity in the spinal cord at 1-day and 5-days time periods after DFP
      administration. We also determined the protein levels of protein kinase C (PKC),
      CaM kinase II and several phosphatases (i.e. phosphatase 1 (PP1), phosphatase 2A
      (PP2A), phosphatase 2B (PP2B) in the spinal cord of DFP-treated hens after 1, 5,
      10, and 20 days). There was increase in CaM kinase II alpha subunit level after
      10 and 20 days of treatment, and decrease in PKC level at 1-day and 20-days time
      periods in spinal cord mitochondria. In contrast, the cerebrum, which is
      resistant to DFP-induced axonal degeneration, did not show change in PKA and CaM
      Kinase II levels at any time period DFP post-administration. No alteration was
      found in the protein levels of PP1, PP2A, and PP2B at any time period. An early
      induction in PKA, which is an important protein kinase in signal transduction,
      followed by that of CaM kinase might be contributing towards the development of
      OPIDN in DFP-treated hens.

PMID- 11451377
TI  - Purification and properties of ferrochelatase from Chironomidae larvae.
AB  - Ferrochelatase with an Mr of 42,700 Da and a pI of 7.35 has been purified to
      homogeneity from chironomidae larvae. The activity of the enzyme reached maximum
      at pH 7.8 and decreased with the increase of pH. The enzyme activity varied with
      temperature and showed maximum activity around 37 degrees C. The purified enzyme
      was active towards protoporphyrin but inactive towards other porphyrins. The
      specific enzyme activity of ferrochelatase from chironomidae is about 10-fold
      higher than that of the rat. Electrophoresis of the purified fractions shows that
      the enzyme contains only one single polypeptide. The soluble ferrochelatase
      contained one mole of iron in each mole of the enzyme. The N-terminal sequence
      analysis of the enzyme shows a high percentage of conserved regions of the enzyme
      among other species. The enzyme properties are similar to those of the mammalian
      ferrochelatases except with slightly higher specific activity. Chironomidae
      ferrochelatase appeared to be more heat resistant and less susceptible than its
      mammalian equivalent to inhibition by lead.

PMID- 11451378
TI  - Effects of arrhythmogenic lipid metabolites on the L-type calcium current of
      diabetic vs. non-diabetic rat hearts.
AB  - Accumulation of lipid metabolites, such as palmitoylcarnitine and
      lysophosphatidylcholine, is thought to be a major contributor to the development
      of cardiac arrhythmias during myocardial ischemia. This arrhythmogenicity is
      likely due to the effects of these metabolites on various ion channels. Diabetic
      hearts have been shown to accumulate much higher concentrations of these lipid
      metabolites during ischemia, which may be an important factor in the enhanced
      incidence of arrhythmias in diabetic hearts. However, it is not known whether
      these metabolites have similar effects on the ion channels of diabetic hearts as
      in non-diabetic hearts. Previous studies on myocytes from non-diabetic hearts
      have reported either enhancement or inhibition of L-type calcium current (I(Ca))
      by these lipid metabolites. Thus, it is not clear whether the effects of
      palmitoylcarnitine and/or lysophosphatidlycholine on I(Ca) contribute to the
      enhanced arrhythmogenicity of diabetic hearts or protect against arrhythmias. We
      determined the effect of exogenous palmitoylcarnitine and lysophosphatidylcholine
      on the (I(Ca)) in ventricular myocytes from streptozotocin-diabetic and non
      diabetic rat hearts under identical conditions. We found that palmitoylcarnitine
      and lysophosphatidylcholine exhibited a dose-dependent inhibition of I(Ca), which
      was virtually identical in diabetic and non-diabetic cardiac myocytes. Thus, we
      conclude that these arrhythmogenic lipid metabolites have similar actions on
      calcium channels in diabetic and non-diabetic hearts. Therefore, the greater
      susceptibility of diabetic hearts to arrhythmias during myocardial ischemia is
      not due to an altered sensitivity of the L-type calcium channels to lipid
      metabolites, but may be explained, in large part, by the greater accumulation of
      these metabolites during ischemia.

PMID- 11451379
TI  - Heat shock preconditioning and pretreatment with glucocorticoid antagonist RU 486
      protect rat myogenic cells H9c2 against glutamate-induced cell death.
AB  - We have observed that the treatment of rat-heart derived H9c2 myoblasts for 20 h
      with the excitatory amino acid glutamate resulted in cell death in a dose
      dependent manner as determined by LDH release. The optimum cardiotoxicity was
      seen at 25 mM glutamate. Preconditioning with either sublethal heat shock (42
      degrees C for 30 min) or pretreatment with 500 nM of the glucocorticoid
      antagonist RU 486 for 24 h almost completely protected H9c2 cells against
      subsequent 20 h treatment with 25 mM lethal glutamate. In addition, we have
      observed that glutamate treatment resulted in intense nuclear localization of
      glucocorticoid receptors (GR) in H9c2 cells as judged by the confocal
      immunofluorescence microscopy. Furthermore, pretreatment with either heat shock
      or RU 486 followed by glutamate treatment resulted in dramatic decrease in GR
      nuclear localization which was almost comparable to that observed with control
      untreated cells. In conclusion, we have shown for the first time using H9c2 cells
      that (i) protection from glutamate cardiotoxicity occurs with prior treatment
      with sub lethal heat shock or RU 486 and (ii) these measures down regulate the
      intense nuclear localization of GR induced by glutamate. The block to GR nuclear
      localization is likely to be involved in cardioprotective effects offered against
      glutamate toxicity by pretreatment with heat shock or RU 486.

PMID- 11451380
TI  - Genomic organization and neonatal expression of the bovine myostatin gene.
AB  - Myostatin belongs to the Transforming Growth Factor-beta (TGF-beta) superfamily
      and is expressed in developing and mature skeletal muscle. Biologically, the role
      of myostatin seems to be extremely well conserved during evolution since
      inactivating mutations in myostatin gene cause similar phenotype of heavy
      muscling in both mice and cattle. In this report we have analysed the genomic
      structure and neonatal expression of the bovine myostatin gene. The molecular
      analysis shows that the bovine myostatin gene consists of three exons and two
      introns. The sizes of the first and second exons are 506 and 374 base pairs (bp)
      respectively. The size of the third exon was found to be variable in length (1701
      or 1812 or 1887 nucleotides), whereas the size of the two introns is 1840 and
      2033 bps. In the first exon of bovine myostatin, a single transcription
      initiation site is found at 133 bps from the translation start codon ATG.
      Sequencing the 3' untranslated region indicated that there are multiple
      polyadenylation signals at 1301, 1401 and 1477 bp downstream from the translation
      stop codon (TGA). Furthermore, 3' RACE analysis confirmed that all three
      polyadenylation sites are used in vivo. Using quantitative RT-PCR we have
      analysed neonatal expression of myostatin gene. In both the M. biceps femoris and
      M. semitendinosus, the highest level of myostatin expression was observed on day
      1 postnatally, then gradually reduced on days 8 and 14 postnatally. In contrast,
      in the M. gastrocnemius, myostatin expression was highest on day 14 and lowest on
      day 8. These results indicate that myostatin gene structure and function is well
      conserved during evolution and that neonatal expression of myostatin in a number
      of predominantly fast twitch muscles is differentially regulated.

PMID- 11451381
TI  - Phorbol ester tumour promoter mediated altered expression and regulation of
      matrix metalloproteinase-2 in a H-ras transformed cell line capable of benign
      tumour formation.
AB  - The matrix metalloproteinases (MMPs) are thought to play key roles in tumour
      formation and malignant progression. The present study demonstrates alterations
      in the regulation of matrix metalloproteinase-2 (MMP-2) expression in response to
      the phorbol ester tumour promoter, PMA, in a H-ras transformed cell line, NR3,
      which is capable of benign tumour formation. PMA treatment of NR3 cells resulted
      in decreased expression of MMP-2 mRNA levels. Following a lag period, an
      accompanying change in gelatinolytic activity was also found. These PMA-mediated
      alterations in MMP-2 mRNA levels were independent of de novo protein synthesis
      and involved both transcriptional and post-transcriptional events. Most notably,
      PMA regulates MMP-2 mRNA expression through a mechanism involving message de
      stabilization. Additionally, protein kinase C mediated events were found to play
      a role(s) in the regulation of MMP-2 message expression in NR3 cells. This study
      demonstrates several novel aspects regarding the regulation of MMP-2 expression
      in a H-ras transformed cell line and thereby provides further insight into the
      altered growth regulatory programs associated with H-ras mediated cellular
      transformation.

PMID- 11451382
TI  - Two dimensional non equilibrium pH gel electrophoresis mapping of cytosolic
      protein changes caused by dietary protein depletion in mouse liver.
AB  - Two-dimensional non-equilibrium pH gel electrophoresis (2D-NEPHGE) analysis was
      used to evaluate the effects of dietary protein depletion on the protein
      composition of mouse liver cytosol. Analysing the cytosol from both normal and
      protein depleted liver, the position in gels of more than three hundred protein
      spots was determined. After 5 days of protein depletion, about 20% of the spots
      either increased or decreased more than 2 fold. Five spots of glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) were recognised by specific antibodies. The
      glutathione S-transferase (GSTs) subunits Ybl, Yc and Yf were identified by the
      simultaneous analysis of both glutathione-binding cytosolic proteins and the
      corresponding standards. As estimated by internal optical density (IOD) of spots,
      the changes caused by protein depletion in GAPDH and GST subunit contents were
      similar to those obtained by other methods. By means of mass spectrometric
      analysis of tryptic peptides generated from spots and/or comparison of two
      dimensional gel electrophoretic patterns, carbonic anhydrase III (CAIII), Cu, Zn
      superoxide dismutase (CuZnSOD) and a cytochrome P450 cytosolic protein (cyt P450)
      were identified. These three proteins, as well as GSTs, are related with
      intracellular detoxification and free radical scavenging systems. Their contents
      were regulated by dietary protein restriction in a manner indicative of
      diminished liver defence against oxidising agents.

PMID- 11451383
TI  - Ubiquitin dependent proteolysis is activated in apoptotic fibroblasts in culture.
AB  - The ubiquitin mediated pathway constitutes an early response in cultured cells
      where apoptosis, assessed by internucleosomal specific DNA fragmentation, was
      induced by serum withdrawal. Data demonstrate that nuclear ubiquitin proteolytic
      system, but not cytoplasmic, is activated. This activation is paralleled by a
      substantial chromatin de-condensation. We suggest that chromatin relaxation is
      causative of the fragmentation since it exposes the DNA to nucleolytic attack.
      Finally, maintenance of homeostasis and induction of apoptosis seem to undergo a
      parallel contemporary pathway with a possible mutual feedback.

PMID- 11451384
TI  - LDL size and susceptibility to oxidation in experimental nephrosis.
AB  - The aim of this study was to investigate the relationship between endothelial
      dysfunction and low density lipoprotein (LDL) size and susceptibility to
      oxidation in nephrotic rats with or without deficiency of vitamin E and selenium.
      Four groups of male Wistar rats were studied: control (C), vitamin E and selenium
      deficient control (DefC), nephrotic (NS), and vitamin E and selenium deficient NS
      (DefNS). Nephrotic syndrome was induced by puromycin aminonucleoside. The molar
      ratio of vitamin E/LDL-cholesterol was significantly lower in DefNS, DefC rats,
      and NS vs. C rats. In comparison with control animals, vasodilation and LDL
      oxidability were significantly lower in nephrotic animals. LDL size was similar
      in all groups. Abnormal endothelial function in response to acetylcholine and
      carbachol was observed in NS animals compared to control rats. Relaxation
      response was inversely associated with an increase in LDL susceptibility to
      oxidation and with a lower molar ratio of vitamin E/LDL-c. LDL oxidability and
      LDL-c were the only variables independently associated with vasodilation. These
      results suggest that endothelial dysfunction of NS may be a consequence of the
      increased LDL susceptibility to oxidation, secondary to antioxidant deficiency.

PMID- 11451385
TI  - Expression of Ca2+/calmodulin-dependent protein kinase II delta-subunit isoforms
      in rats with hypertensive cardiac hypertrophy.
AB  - Myocardial hypertrophy is characterized by abnormal intracellular Ca2+ handling
      and decreased contractile performance. Ca2+/calmodulin-dependent protein kinase
      II (CaMKII) phosphorylates numerous Ca2+ handling proteins and thus can regulate
      intracellular Ca2+ homeostasis directly. We therefore investigated whether
      differential expression of CaMKII isoforms occurs with cardiac hypertrophy which
      might promote an abnormal intracellular Ca2+ homeostasis. We further investigated
      the potential influence of angiotensin (Ang) II on CaMKII expression levels.
      Hearts from adult Spontaneously Hypertensive Rats (SHR) and hearts from two
      transgenic rat models with Ang II-dependent hypertension were studied. The
      expression of the cardiac CaMKII isoforms delta2, delta3, delta4 and delta9 was
      determined by RT-PCR and immunoblot methods. Rats transgenic for the mouse Ren-2
      gene (mrTGR), SHR and controls were studied at the age of 6 months and rats
      transgenic for the human renin-angiotensin system (hrTGR) from postnatal day 1 to
      week 8. SHR and mrTGR had an increased heart/body weight ratio (26 and 25%)
      compared with controls (p < 0.05). SHR hearts showed significantly increased mRNA
      levels of delta4 and delta9 (p < 0.05) with no change for delta2 and delta3.
      mrTGR hearts had a significantly increased delta4 and a significantly decreased
      delta3 transcript level (p < 0.05) with no change for delta2 and delta9. hrTGR
      hearts developed severe hypertrophy (42%) after postnatal day 14. The neonatal
      delta2, delta3 and delta4 isoform expression levels were higher (30-100%)
      compared with SD controls. The levels decreased with increasing age and equalized
      to controls at week 8, except for delta4 which started to increase after week 4
      (p < 0.05). CaMKIIdelta protein levels of all cardiac hypertrophy models were
      increased in sarcoplasmic reticulum preparations (50-120%) compared with controls
      (p < 0.05) while the cytosolic levels remained unchanged. Thus, CaMKIIdelta
      isoforms are differentially expressed in cardiac hypertrophy. The fetal delta4
      isoform was constantly expressed. CaMKIIdelta adopts the fetal phenotype
      independent of the type of hypertrophic stimulus. The observed alterations of
      CaMKIIdelta isoform patterns may affect intracellular Ca2+ homeostasis and thus
      contribute to the abnormal contractile phenotype of cardiac hypertrophy.

PMID- 11451386
TI  - Changes in HSP70 and P53 expression are related to the pattern of
      electromechanical alterations in rat cardiomyocytes during simulated ischemia.
AB  - The objective was to relate the response of the HSP70 and P53 genes to the
      cessation and the recovery of cardiac muscle cell functions when submitted to
      ischemia-reperfusion. We have measured the electromechanical activity, the
      released enzymes and HSP70 RNA and protein levels in cultured neonatal rat
      cardiomyocytes (CM) in a substrate-free, hypoxia-reoxygenation model of ischemia
      reperfusion. In parallel the expression of the two genes P53 (the key apoptosis
      regulator gene) and P21/Waf1 (the P53 target gene) has been evaluated. The
      functional recovery during post-'ischemic' reoxygenation was associated with an
      overexpression of HSP70 and P53 lasting until the functional parameters reverted
      back to the normal, prehypoxic values. In contrast, extending the substrate-free
      hypoxic treatment worsens the dysfunction of the cardiac muscle cell and, in
      these conditions, reoxygenation failed to restore cell functions and to activate
      HSP70. Finally, in the conditions of reversible 'ischemic' cell injury, an early
      and transitory activation of P53 was associated with the functional recovering
      process of the CM submitted to simulated ischemia. These observations are
      suggestive of a contributive role of both HSP70 and P53 to a cytoprotective
      program activated by reoxygenation in post-'ischemic' CM.

PMID- 11451387
TI  - Estrogen increases hepatic lipase levels in inbred strains of mice: a possible
      mechanism for estrogen-dependent lowering of high density lipoprotein.
AB  - We have shown mouse to be an useful animal model for studies on the estrogen
      mediated synthesis and secretion of lipoproteins since, unlike in rats, low
      density lipoprotein receptors are not upregulated in mice. This results into the
      elevation of plasma levels of apolipoprotein (apo) B and apoE, and lowering of
      apoA-1-containing particles. The mechanisms of apoB and apoE elevation by
      estrogen have been elucidated, but the mechanism of lowering of plasma levels of
      HDL is still not known. Among other factors, apoA-I, cholesterol ester transfer
      protein (CETP), scavenger receptor B1 (SR-B1), and hepatic lipase are potential
      candidates that modulate plasma levels of HDL. Since estrogen treatment increased
      hepatic apoA-I mRNA and apoA-I synthesis, and mouse express undetectable levels
      of CETP, we tested the hypothesis that estradiol-mediated lowering of HDL in mice
      may occur through modulation of hepatic lipase (HL). Four mouse strains (C57L,
      C57BL, BALB, C3H) were administered supraphysiological doses of estradiol, and
      plasma levels of HDL as well as HL mRNA were quantitated. In all 4 strains
      estradiol decreased plasma levels of HDL by 30%, and increased HL mRNA 2-3 fold.
      In a separate experiment groups of male C57BL mouse were castrated or sham
      operated, and low and high doses of estradiol administered. We found 1.4-2.5 fold
      elevation of HL mRNA with concomitant lowering of HDL levels. Ten other mouse
      strains examined also showed estradiol-induced elevation of HL mRNA, but the
      extent of elevation was found to be strain-specific. Based on these studies, we
      conclude that hepatic lipase is an important determinant of plasma levels of HDL
      and that HL mRNA is modulated by estrogen which in turn may participate in the
      lowering of plasma levels of HDL.

PMID- 11451388
TI  - Phosphorylation of prolidase increases the enzyme activity.
AB  - Prolidase [EC 3.4.13.9] is a ubiquitously distributed imidodipeptidase that
      catalyzes the hydrolysis of C-terminal proline-containing dipeptides. The enzyme
      plays an important role in the recycling of proline for collagen synthesis and
      cell growth. Although, the increase in the enzyme activity is correlated with
      increased rate of collagen turnover, the mechanism by which prolidase is
      regulated remain largely unknown. In the present study we found that
      phosphorylation of fibroblast's prolidase may be an underlying mechanism for up
      regulation of the enzyme activity. Supporting evidence comes from the following
      observations: (1) immunoprecipitated prolidase was detected as a phosphotyrosine
      protein as shown by western immunoblot analysis, (2) tyrosine kinase inhibitor
      erbstatin induced (in a dose dependent manner) a decrease in prolidase activity
      in cultured human skin fibroblasts, (3) anti-phosphotyrosine antibody reduced and
      phosphotyrosine phosphatase 1B antibody (anti-PTP 1B) increased (in a dose
      dependent manner) the prolidase activity in extract of fibroblast's homogenate,
      (4) decrease in prolidase activity from collagenase treated or serum starved
      fibroblasts can be partially prevented by incubating fibroblast's homogenate
      extract with anti-PTP 1B antibody. These results provide evidence that prolidase
      is phosphotyrosine enzyme and suggest that the activity of prolidase may be up
      regulated by the enzyme phosphorylation.

PMID- 11451389
TI  - Handheld digital equipment for weight composite distress paradigms: new
      considerations and for rapid documentation and intervention of rodent
      populations.
AB  - Animal care in the third millennium will require a melding of scientific and
      humane interests to achieve optimal care of genetically engineered mice and to
      expedite scientific and medical advances by using these mammals. Undoubtedly,
      rodent patients present certain difficulties for those who wish to assess their
      daily well-being and to contribute to efficient and successful scientific
      discovery. High-density housing, large experimental groups, and low-lux room
      lighting makes the application of large-animal care standards to rodents seem
      daunting to researchers and veterinary care programs. In addition, great
      variability in training and experience among those responsible for the direct
      application of humane care to rodents exists. Most of the direct animal care in
      small animal facilities occurs in decentralized locales by personnel who have
      completed obligatory but relatively minimal animal care training. Examples of
      personnel in this category include postdoctoral fellows, junior-level scientists,
      summer students, and assistant laboratory animal technologists. Some programs
      even use the husbandry staff to perform health checks of high-risk populations on
      a daily basis. For this reason, the extrapolation of performance-based
      intervention in rodent care is difficult to apply practically. Early efforts to
      enhance humane outcome in rodents have been published by scientists and
      veterinarians and are largely directed at singular endpoints, such as weight loss
      and declining temperatures, in specific models. Scientists often are reluctant to
      accept such standards because of concern about premature intervention or
      variability between scorers and to reservations regarding a lack of procedural
      likeness with their proposed study. This paper highlights a digital method for
      melding current advanced animal scoring standards using palm pilot user-friendly
      methods that account for composite weight scoring, behavioral or physiologic
      attributes, and interventions. Information is rapidly downloaded and results in
      quick storage of large rodent population monitoring. This minimizes
      interpretative variability between caregivers and greater standardization of
      procedures. These considerations facilitate the rapid diagnosis of outliers and
      make possible intervention that streamlines the delivery of humane care to large
      experimental populations.

PMID- 11451390
TI  - Recovery from carotid artery catheterization performed under various anesthetics
      in male, Sprague-Dawley rats.
AB  - This study was designed to determine the time to recovery from carotid artery
      catheterization using multiple criteria and to compare recovery times between
      three common anesthetics. Male Sprague-Dawley rats, chronically instrumented with
      radio-telemetry transmitters, were anesthetized with sodium pentobarbital,
      halothane or a mixture of ketamine, xylazine and acepromazine before an
      indwelling catheter was placed in the carotid artery. The procedure was completed
      in less than 15 min. Changes in body weight, food and water consumption, blood
      pressure, heart rate and activity were used to determine recovery. As judged by
      recovery of body weight, animals anesthetized with each of the anesthetics
      recovered by the 4th day after catheterization. Food and water consumption
      normalized by 1-2 days after surgery. Heart rates and blood pressures during the
      light phase of the photoperiod were significantly increased for 2 days by all
      anesthetics. During the dark phase of the photoperiod, heart rates and blood
      pressures were not significantly affected by pentobarbital or halothane
      anesthesia, but were significantly decreased and increased respectively on the
      night immediately following surgery in the ketamine / xylazine / acepromazine
      anesthetized rats. Delayed elevations of heart rate were observed in
      pentobarbital and halothane anesthetized rats on days and/or nights 5 and 6 post
      surgery. Animal activity patterns during the light phase of the photoperiod were
      not affected by pentobarbital or halothane, but were increased by ketamine 2 days
      after surgery. During the dark phase, halothane transiently reduced activity
      whereas ketamine-anesthetized rats showed reduced activity for 4 nights post
      surgery. These studies show that recovery depends on the criteria selected and
      the anesthetic used, but, in general, 2-4 days were required for recovery from
      this relatively simple procedure.

PMID- 11451391
TI  - Testing and comparison of non-opioid analgesics in amphibians.
AB  - Because of the lack of information about effective analgesics in non-mammalian
      vertebrates, the potency of various non-opioid agents were tested in a model of
      analgesia by using Northern grass frogs (Rana pipiens). This alternative model
      has been used widely for investigating opioid analgesic action. Potential non
      opioid analgesics tested included antipsychotic, benzodiazepine, barbiturate,
      antihistamine, non-steroidal anti-inflammatory (NSAID), and partial opioid
      agents. Northern grass frogs were acclimated to lab conditions in individual
      cages. Drugs were administered systemically through the dorsal lymph sac, and
      analgesic effects were estimated by using the acetic acid test (AAT). The AAT is
      done by placing logarithmic dilutions of acid dropwise on the dorsum of the
      animal's thigh until a wiping response is obtained. At various doses,
      chlorpromazine and haloperidol (antipsychotics), chlordiazepoxide (a
      benzodiazepine), buprenorphine (a partial opioid agonist), and diphenhydramine (a
      histamine antagonist) produced moderate to strong analgesic effects. Indomethacin
      and ketorolac (NSAIDs), butorphanol (a partial opioid agonist), and pentobarbital
      (a barbiturate) produced weaker but noticeable analgesic effects. Our results are
      the first to document the effectiveness of a wide array of pharmacologically
      active agents in a novel amphibian model for analgesia. These findings provide
      needed data regarding the use of alternative, non-opioid agents for the treatment
      of pain in amphibians and other poikilothermic species.

PMID- 11451392
TI  - Rescue of a transgenic mouse line by transplantation of a frozen-thawed ovary
      obtained postmortem.
AB  - During the course of breeding valuable mutant or transgenic mice, deaths
      sometimes occur due to sudden-onset disease or accident. We previously showed
      that mice can be rescued by transplantation of ovaries taken up to 2 h after
      death from dead mice remaining at conditions of constant temperature (22 +/- 2
      degrees C) and humidity (55% +/- 5%). To extend the flexibility of
      transplantation, we assessed whether it is possible to cryopreserve ovaries taken
      from dead mice within 2 h after death. Fertile transgenic mice used as donors
      were euthanized by cervical dislocation and left for 2 h after death. The
      cryopreservation was based on Sztein's method with a controlled-rate freezer or
      on Rall and Fahy's method without a controlled-rate freezer. The recipient mice
      were nontransgenic littermates of the donor mice, and after transplantation of
      the frozen-thawed ovaries, they were mated with proven-fertile males. Polymerase
      chain reaction (PCR) analysis confirmed that the progeny carried the transgene.
      We show here that by using both of the described methods, it is possible to
      cryopreserve the ovaries taken from dead mice within 2 h after death and that the
      mice into which the cryopreserved ovaries are transplanted are fertile.

PMID- 11451393
TI  - Exclusion of mouse hepatitis virus from a filtered, plastic rodent shipping
      container during an in transit field challenge.
AB  - Although leading suppliers of laboratory mice and rats continue to use filtered
      shipping boxes to protect their animals from contamination during transport to
      the end user, no information had been available in the literature to demonstrate
      that any of these boxes actually accomplish this task. To test this hypothesis,
      12 plastic shipping boxes with filters and tight-fitting lids and six cardboard
      shipping boxes without filters (controls) were each stocked with adult,
      adventitious disease-free mice. All 18 shipping boxes were transported to a
      facility housing a breeding colony of mice enzootically infected with four murine
      viruses, including mouse hepatitis virus (MHV), and were placed inside the colony
      for 15 h. The boxes were then transported to a commercial testing laboratory, at
      which the animals were aseptically removed and were held in microisolation cages
      for 28 days, after which their sera tested for antibody to all four murine
      viruses. All serum samples from mice held in the control boxes were positive for
      antibody to MHV, whereas sera from all mice held in filtered boxes were negative
      for antibody to any of the four viruses. This study demonstrates that at least
      one type of filtered shipping container protects mice from a field challenge of
      MHV. To the best of our knowledge, this is the first documentation of any
      microbial efficacy testing conducted on filtered shipping containers for
      laboratory animals.

PMID- 11451394
TI  - The effects of overnight fasting, feeding, or sucrose supplementation prior to
      necropsy in rats.
AB  - This study was designed to investigate the acute effects on routine hematology,
      serum biochemistry, gastrointestinal contents and weight, and liver weight and
      morphology due to overnight sucrose feeding of rats prior to necropsy. Groups of
      rats (five males and five females/group) were fasted overnight, fed chow, or fed
      sucrose and were euthanized approximately 17 h later. At necropsy, blood was
      obtained for hematology and serum biochemistry profiling, and the livers and
      gastrointestinal tracts were weighed and examined. The livers also were evaluated
      microscopically. The blood glucose and urea nitrogen concentrations and liver
      weights of animals fed sucrose differed significantly from those of the other
      groups. Alterations were more striking in males than females. Marked histological
      changes were present in livers from animals fed sucrose prior to necropsy
      compared with fasted or chow-fed animals, and these changes were attributed to
      increased glycogen deposition in the sucrose-fed animals. Because of alterations
      in hepatic structure and function, we cannot recommend the practice of feeding
      sucrose to rats prior to necropsy for toxicology studies or any studies examining
      hepatic function.

PMID- 11451395
TI  - Postnatal development of penile NADPH diaphorase in male rats (Rattus
      norvegicus): an indicator of erectile function.
AB  - The aim of this study was to determine the contribution of nitric oxide (NO) to
      the development of penile erection in rats and was accomplished by evaluating the
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH) content of
      juvenile penile tissues. NADPH is an enzyme involved in the synthesis of NO, a
      mediator of smooth muscle relaxation in penile tissues. We euthanized 36 rats
      (age, 1 to 65 days) and obtained penile midshaft specimens for NADPH staining.
      The number of NADPH-positive granules in the corpus cavernosum and dorsal penile
      nerve increased significantly (P < 0.001) until animals were 50 days of age.
      Penile erections in young rats are known to occur around 30-40 days, and penile
      tissues showed a very significant (P < 0.001) increase of NADPH-positive granules
      in the corpus cavernosum and the dorsal penile nerve during this period.
      Therefore, NO seems important for the development of penile erection in juvenile
      rats.

PMID- 11451396
TI  - Chronic myelocytic leukemia in a juvenile rhesus macaque (Macaca mulatta).
AB  - Myeloid neoplasia has been studied extensively in human beings but has not been
      reported in macaques. A 2-year-old female rhesus macaque that was experimentally
      exposed to lead as a neonate, was noted to have immature circulating myelocytic
      cells, including 1% blasts, and normocytic normochromic anemia on a blood sample
      obtained for monthly health monitoring. The animal was treated with hydroxyurea,
      blood transfusion, and recombinant human erythropoietin to reduce the
      leukocytosis and correct the anemia. The disease had a relatively indolent course
      for 3 months, when it progressed to blast crisis. After the onset of blast
      crisis, the animal was euthanized because of bleeding problems, anemia, and a
      progressive decline in her health. The animal was negative by serology,
      polymerase chain reaction (PCR) assays, and/or culture for simian retrovirus
      (SRV), simian T-lymphotropic virus type I (STLV-I), and simian immunodeficiency
      virus (SIV). PCR assay for the bcr-ABL chromosomal translocation using primers
      made for the human gene was negative. Serology for Epstein-Barr virus (EBV)-like
      viruses was positive for IgG directed against the viral nucleocapsid antigen, but
      epidemiologic factors make it unlikely that the leukemia was associated with EBV
      induced viral transformation. Lead exposure has been associated with neoplasia in
      human beings, and the possible role of neonatal lead exposure in hematologic
      neoplasias deserves further scrutiny.

PMID- 11451397
TI  - Unexpected deaths in young New Zealand white rabbits (Oryctolagus cuniculus).
AB  - Five weeks after the arrival of a batch of six New Zealand White rabbits for use
      in antisera production, four died unexpectedly within a 48-h period. Necropsy
      findings showed a consistent pattern of liver pathology in all animals, with
      multiple miliary abscesses in all liver lobes. Of the remaining two animals in
      the cohort, one showed weight loss, mild jaundice, and ascites, and the other
      rabbit had only weight loss. The differential diagnosis for these unexpected
      deaths included parasitic and bacterial infections. Histopathologic examination
      of the liver confirmed a diagnosis of hepatic coccidiosis. The possible origin of
      the coccidia responsible for this outbreak is discussed.

PMID- 11451402
TI  - Response properties of periodontal mechanosensitive neurones in the rat
      trigeminal sensory complex projecting to the posteromedial ventral nucleus of the
      thalamus.
AB  - Unitary discharges from periodontal mechanosensitive (PM) neurones responding to
      mechanical stimulation of the tooth were recorded from the trigeminal sensory
      complex in the rat brainstem. Of the PM units recorded, 22% were activated by
      antidromic stimulation of the contralateral (20%) or ipsilateral (2%)
      posteromedial ventral nucleus of the thalamus. Although thalamic-projecting
      neurones were recorded extensively throughout the trigeminal sensory complex,
      they originated most often in the region from the caudal main sensory nucleus to
      the rostral subnucleus oralis of the trigeminal spinal tract nucleus. The
      response latencies of the rostral nucleus units to orthodromic stimulation of
      peripheral receptive fields and antidromic stimulation of the thalamus were
      significantly shorter than those of the caudal nucleus units. More than half were
      single-tooth units originating from incisor teeth. They responded continuously
      when pressure was applied to the tooth. The magnitude of the response varied with
      the direction of the stimulus. Maximal responses were obtained when the stimulus
      was applied labiolingually or vice versa. The threshold for mechanical
      stimulation of the tooth was less than 0.05 N. The rostrocaudal distribution and
      response properties of thalamic-projecting PM neurones were very similar to those
      of non-thalamic-projecting PM units that were not activated by antidromic
      stimulation of the thalamus.

PMID- 11451403
TI  - Histomorphometric study of the periodontal vasculature during and after
      experimental tipping of the rat incisor.
AB  - The periodontal vasculature encircling the entire length of the rat lower incisor
      was studied at the time of tipping movement and 3 months later. In 12 rats (212+/
      4 g b.w.), loads (0.19+/-0.016 N) were applied to the lower left incisor in a
      linguointrusive direction. After 2 weeks of loading, six experimental animals
      were killed with the loading springs in place. The springs were removed in the
      six remaining rats, which were killed 12 weeks later. Six additional rats with
      intact teeth served as control. All incisors were fixed, demineralized, embedded
      in glycol methacrylate and cross-sectioned perpendicular to the long axis of the
      tooth. The distance of each section (2 microm) from the apex was calculated. A
      computerized image-analysis program was used to measure the width and area of the
      labial and lingual periodontal ligament to establish whether the measured
      segments corresponded to the compressed or expanded zones. In each cross-section,
      the various types of blood vessels were counted and the cross-sectional area of
      all venous vessels was measured. The results showed that after 2 weeks of loading
      (1) the general trend of vascular changes was similar under pressure and tension;
      (2) the large-diameter vessels were unaffected by loading; (3) the mean number of
      terminal arterioles had decreased significantly, while the number of capillaries
      and postcapillary venules had increased significantly in the apical tooth part;
      (4) the venous blood vessel area had decreased significantly in the apical tooth
      part; (5) the intensity of the vascular reaction was dependent on the degree of
      tissue distortion; and (6) after 12 weeks' recovery the vascular changes were
      still present, demonstrating a rebound effect. The findings suggest that
      microvascular alterations following tooth loading are not directly related to the
      spatial effect of loading itself and are of a much longer duration than expected.

PMID- 11451404
TI  - Immunohistological study of interferon-gamma- and interleukin-4-bearing cells in
      human periodontitis gingiva.
AB  - The purpose was to investigate the balance between interferon (IFN)-gamma- and
      interleukin (IL)-4-bearing cells in various human inflamed gingiva by
      immunohistochemistry. Gingival tissues obtained from patients with gingivitis or
      periodontitis were divided into three groups based on the degree of
      histopathological inflammation, mild, moderate and severe. The tissues were also
      divided into four groups according to the clinical probing depth (PD). IFN-gamma-
      and IL-4-bearing cells in gingival tissues were stained immunohistologically and
      counted. The ratio of IL-4-bearing cells to IFN-gamma-bearing cells was
      calculated for each section. IFN-gamma-bearing cells were widespread in the
      connective tissue and their number increased significantly with the severity of
      inflammation and an increase of PD. IL-4-bearing cells were located beneath the
      pocket epithelium and their number showed no significant differences among the
      inflammation or PD groups. The ratios of IL-4-bearing cells to IFN-gamma-bearing
      cells in the severe inflammation or deep PD groups were significantly lower than
      those in the moderate inflammation or shallow PD groups. These results suggest
      that a low ratio of IL-4-bearing cells to IFN-gamma-bearing cells might be
      involved in the destruction of periodontal tissue.

PMID- 11451405
TI  - Cell population growth in the rat parotid gland during postnatal development.
AB  - The growth kinetics of different cell populations in the rat parotid was studied.
      The evolution of the frequency and absolute number of each cell type was
      determined morphometrically by a particle-counting method and the evolution of
      the [(3)H]thymidine labeling indices of the same cell types was determined by
      autoradiography. The data obtained for the evolution of cell number in each gland
      compartment, i.e. acini, intercalated ducts, striated ducts and stroma, were
      adjusted by exponential equations, permitting estimation of the effective cell
      accumulation rate in the compartment for each population, i.e. the mean
      population duplication time (T(D)). In addition, the cell production rate in each
      gland compartment was determined using the mean labeling index for the period
      studied and a mathematical estimation of the mean cell generation time (T(G)),
      assuming an exponential growth pattern for the acinar, intercalated duct and
      striated duct populations during the period from 5 to 20 days of postnatal
      development. Analysis of the relation between effective cell accumulation (T(D))
      and presumed cell production (labeling index and T(G)) for each intralobular
      parenchymal compartment of the rat parotid during this period suggests that the
      proliferative activity of the acinar cell population was sufficient to guarantee
      marked growth of its compartment and provided cells that presumably
      dedifferentiated into intercalated duct cells, whereas cells produced in the
      intercalated duct compartment migrated to, and differentiated into, cells of the
      striated duct compartment.

PMID- 11451406
TI  - Skull size and cheek-tooth length in wild-caught and captive-bred chinchillas.
AB  - Chinchillas are herbivorous rodents with teeth that all grow continuously. In
      captivity, they are commonly affected by dental disease. As the range of dental
      disease occurring in wild chinchillas is unknown, the dentition of museum
      specimens originally obtained from the wild was assessed and compared with
      specimens prepared from captive-bred animals. Skulls from wild-caught chinchillas
      showed minimal evidence of dental disease and the teeth were all short, cheek
      tooth lengths averaging 5.9 mm. Cheek-tooth lengths in zoo specimens (average 6.6
      mm), clinically normal (average 7.4 mm) and captive-bred animals with dental
      disease (average 10 mm) were significantly elongated by comparison (P<0.0001).
      Captive-bred specimens showed a wide range of tooth-related lesions. These
      results suggest that some aspect of captivity is responsible for the development
      of dental disease in chinchillas. It is suggested that the diet (its physical
      form and composition) is the main aetiological factor, and that provision of a
      diet closely matching that of wild chinchillas should significantly reduce the
      incidence of dental disease in captive animals.

PMID- 11451407
TI  - Synchronous recording of load-deformation behaviour and polarized light
      microscopic images of the rabbit incisor periodontal ligament during tensile
      loading.
AB  - Tooth-periodontal ligament-bone segments were cut in the form of rectangular
      prisms (1.5 mm wide, 0.65 mm thick, and long enough to allow anchorage of the
      bone and tooth-end portions in a stretching jig) from the mandibular incisors of
      10 rabbits. The experimental set-up enabled simultaneous recording, on video, of
      the changing image brightness under polarizing optics together with extension
      across the periodontal ligament. Specimens were stretched until failure at a
      velocity of 0.5 mm/min. The tensile load-deformation curve of the ligament
      exhibited an initial, non-linear region that was followed by a linear region, a
      subsequent yielding region preceding the maximum point, and a final descending
      region. Gradual increases in the intensity of birefringence in the linear and
      yielding regions indicated that stress concentrations occur in the supporting
      fibres attached to mineralized tissues. In the final descending region of the
      curve, progressive breakages of individual fibre bundles occurred, mainly in the
      middle zone of the ligament. Analysis of the polarized light-microscopic images
      showed that the increases in brightness and area of birefringent collagen fibre
      bundles occurred in parallel with the stress generated. These results suggest
      that the collagen fibre bundles became aligned with the direction of loading and
      the intensity of their birefringence increased according to the applied tensile
      force.

PMID- 11451408
TI  - The distribution pattern of the hyaluronan receptor CD44 during human tooth
      development.
AB  - The aim was to investigate the expression pattern of the major cell-surface
      hyaluronan receptor CD44, as there are no existing data on its presence or
      absence in human dental structures at different developmental stages.
      Immunohistochemical localization of CD44 was studied using a monoclonal antibody,
      H3, that specifically recognizes an epitope in the common backbone of all CD44
      isoforms. The dental lamina displayed a strong CD44 signal; the external enamel
      epithelium was negative. In the coronal region of the tooth germ the presecretory
      ameloblasts showed an intense reaction whereas the less differentiated inner
      enamel epithelial cells showed no signal at the cervical loop where they meet the
      external enamel epithelium. In the stellate reticulum a moderate reaction was
      detected. The secretory ameloblasts and the stratum intermedium showed a strong
      cell-surface CD44 signal. A strong signal was also observed on the odontoblasts
      and their processes. In the pulp, close to the odontoblastic layer, weak
      labelling was seen in the walls of capillary vessels. The distribution of CD44 in
      the human tooth germ corresponds to that of hyaluronan in most locations,
      suggesting that during tooth development this transmembrane protein plays an
      important part in hyaluronan-mediated events.

PMID- 11451409
TI  - Expression of 25 kDa heat shock protein by synovial type B cells of the mouse
      temporomandibular joint.
AB  - Earlier studies have demonstrated immunoreactivity for heat shock protein 25
      (Hsp25) in type B synovial lining cells of the rat temporomandibular joint, and
      also the presence of characteristic cytoplasmic processes in these cells, but it
      is unclear whether or not the type B cells in other animals possess such
      elaborate cytoplasmic projections and as there is as yet no evidence for the
      synthesis of this protein by these cells. For these reasons, the expression of
      Hsp25 was investigated in the synovial membrane of the mouse temporomandibular
      joint by immunocytochemistry and by in situ hybridization using a specific cRNA
      probe. Intense immunoreaction for Hsp25 was found in the cytoplasm of certain
      synovial lining cells that were identified as type B by immunoelectron
      microscopy. These Hsp25-positive cells had slender cytoplasmic processes, either
      projecting towards or covering the synovial surface. Morphological differences
      between cytoplasmic processes seemed to depend on the location of the type B cell
      bodies. In situ hybridization showed intense signals for Hsp25 mRNA in the
      synovial lining cells, suggesting that the type B cells produce, rather than
      resorb, Hsp25. These findings indicate that Hsp25 is a useful marker for the
      identification of the synovial type B cells in the temporomandibular joint. It is
      further hypothesized that Hsp25 in type B cells is involved in maintaining their
      specific profile and epithelial-like arrangement, and in protecting against
      mechanical stress.

PMID- 11451410
TI  - mRNA expression of membrane-fusion-related proteins in rat parotid gland.
AB  - The soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein (SNAP)
      receptor (SNARE) hypothesis has been applied to exocytosis in salivary glands.
      The expression of SNARE proteins has not been well investigated in the parotid
      gland. In this study, the mRNA expression of SNAREs and membrane-fusion-related
      proteins were investigated in the rat parotid by reverse transcriptase-polymerase
      chain reaction (RT-PCR). All syntaxins except syntaxin 1, and the vesicle
      associated membrane proteins (VAMP) except VAMP-7, NSF, SNAP-23 and alpha-SNAP,
      were expressed for the SNAREs in rat parotid. Synaptotagmins 3, 4 and 11, Munc18s
      (1, 2 and 3), syncollin, prenylated Rab acceptor (PRA1), zygin 1, pantophysin and
      cellugyrin, which are the other membrane-fusion-related proteins, were also
      detected, but neither Rim nor rabphilin 3A, which have high specificity of
      binding to Rab 3A, were found. mRNA expressions of many SNAREs and of the
      membrane-fusion-proteins suggest novel interactions for the regulation of
      salivary exocytosis.

PMID- 11451411
TI  - Missing lateral incisors in Iron Age South-East Asians as possible indicators of
      dental agenesis.
AB  - The absence of lateral incisors is generally a reflection of agenesis or
      hypodontia, with a significant genetic basis and possibly environmental influence
      on the phenotypic expression. A human skeletal sample from the Iron Age cemetery
      of Noen U-Loke in Thailand has a very high prevalence at 79% of adults (30/38)
      with at least one incisor missing in either maxilla or mandible. If the cause of
      this high rate is genetic, it may be indicative of homogeneity, and, therefore,
      endogamy and probably isolation, of the population represented. Supporting
      agenesis as the explanation for this is the lack of space between the central
      incisors and canines in more than half the cases. An alternative explanation is
      that the teeth may have been lost during life through pathology or deliberate
      removal (ablation). There is no evidence in the form of remodelled lesions for
      pathological loss of the teeth. Although there were no significant differences
      between males and females in the numbers of teeth missing, there were significant
      differences in the patterns of loss, with males having more missing teeth on the
      right and females more on the left. No evidence was found in the clinical
      literature of agenesis involving side preference by sex, so this may indicate
      deliberate removal of the teeth. Males were also more likely than females to have
      no space for the missing teeth. Ablation of teeth has been recorded in other
      prehistoric South-East Asian populations but in these cases the evidence was much
      clearer. Agenesis seems to offer the most likely explanation for the missing
      teeth at Noen U-Loke and if so, indicates that a small, isolated population may
      develop a very high rate of hypodontia, with a side preference dependent on sex.

PMID- 11451412
TI  - The spatial and temporal expression of calretinin in developing rat molars
      (Rattus norvegicus).
AB  - Calretinin is a 29-kDa calcium-binding protein abundantly expressed in central
      and peripheral neural tissues. The aim here was to determine its expression
      during various stages of odontogenesis. Five categories of embryonic (E) and
      postnatal (P) rats at various ages (E17, E18, E20, P0, and P7), both male and
      female, were used to represent the various stages of molar tooth development. The
      heads of the experimental animals were harvested at the appropriate time and each
      was cut mid-sagittally and coronally to locate the tooth germs. Selected sections
      were stained immunohistochemically with polyclonal rabbit anticalretinin at a
      concentration of 1:25 after microwave irradiation. The results showed that
      calretinin is distributed widely in epithelium-derived tissues during
      odontogenesis in rat molar tooth germs. It was expressed focally in the dental
      lamina, outer enamel epithelium, stellate reticulum and stratum intermedium at
      different stages. In contrast, it was expressed diffusely and intensely in the
      inner enamel epithelium and presecretory ameloblasts, although it was
      discontinuous over the cusp tips. In the secretory ameloblasts, the staining was
      less intense, being restricted to the cytoplasm, including Tomes' processes. This
      distribution suggests that calretinin may play a part in enamel formation.

PMID- 11451413
TI  - The effect on human salivary fluoride concentration of consuming fluoridated salt
      containing baked food items.
AB  - Salt fluoridation is recognised world-wide as a proven and viable alternative
      means of consumer choice-related, community-based fluoridation where water
      fluoridation is either technically or politically impossible. However, as most
      salt consumed is contained within cooked food products, rather than sprinkled
      over prepared food at the table, the purpose of this study was to investigate the
      effects on salivary fluoride concentration of consuming baked food products
      prepared with 250 and 350 ppm fluoridated salt (as KF). Six food items were baked
      with (a) normal non-fluoridated salt, (b) 250 mg F/kg salt and (c) 350 mg F/kg
      salt. Eleven adult volunteers consumed these foodstuffs on separate occasions and
      salivary samples were collected for fluoride analyses before and at various time
      points (1-30 min) after eating. For most foodstuffs, small but significant
      increases in salivary fluoride concentration occurred for at least 5 min after
      ingestion of the fluoridated salt-containing items. Salivary fluoride
      concentrations peaked 1 or 2 min after eating, with highest values for the six
      test foods ranging from 0.16 to 0.25 ppm F, and from 0.18 to 0.44 ppm F for the
      250 and 350 mg F/kg salt products, respectively. In all cases, salivary fluoride
      concentrations had returned to baseline by 20 min. The clinical significance of
      such small, short-term increases in salivary fluoride is uncertain, but the
      findings suggest that a more frequent intake of foods with fluoridated salt
      substituted for normal salt could help sustain slightly elevated salivary
      fluoride concentrations for more prolonged periods of the day, and might thus
      potentiate the cariostatic effects of saliva on tooth mineral.

PMID- 11451414
TI  - The role of carbohydrate in the assembly and function of polymeric IgG.
AB  - The carbohydrate present on glycoprotein can influence their biologic and
      functional properties. In the present paper we have assessed the role of
      oligosaccharides in the polymerization and effector functions of IgG with the 18
      amino acid extension of IgM added to its carboxy terminus (IgGmutp). We found
      that IgG1mutp and IgG3mutp lacking the carbohydrate addition site in C(H)2, in
      the tail-piece or both assembled into polymers as well as the glycosylated
      versions. Aglycosylated polymers retained the ability to activate complement as
      assayed by C1q binding and hemolysis, although they were not as effective as
      their wild type polymer counterparts. Although IgGmutp lacking the carbohydrate
      in the tail-piece was able to bind to FcgammaRII, completely aglycosylated
      polymers lost the ability to bind to both FcgammaRI and FcgammaRII, suggesting a
      critical role for the C(H)2 sugar in FcR binding. Absence of the mutp
      carbohydrate increased the half life of polymeric IgG1, whereas absence of the
      carbohydrate in C(H)2 accelerated the clearance rate.

PMID- 11451415
TI  - Hidden variables: unstable Abeta chain genes encoding antigen recognition
      structures in tumor survivors.
AB  - Novel single exon genes Abeta4-7 comprising the Abeta6 gene family have been
      cloned from mouse mutants surviving transplantable metastatic tumors. Their
      protein coding sequences are similar to H2-Ab cDNA which encodes antigen-binding
      molecules of antigen presenting cells (APC); their promoters and/or signal
      sequences are unrelated to Ab sequences but found in other eukaryotic genes.
      Abeta4(b) protein was demonstrated on macrophages and B cells that are APC. The
      Abeta6(w302) appears to be an ancient gene ancestral to major histocompatibility
      complex (MHC) class II beta genes. However, unlike the MHC class II, the Abeta4-7
      genes are not involved in skin graft rejection. Despite inbreeding, the
      Abeta6(w302) locus remains unfixed in several strains of mice. The number of
      Abeta genes and their alleles varied between individual mice; they do not map
      into the H2 region but appear to be scattered over the genome. The Abeta6 gene
      family is molecularly unstable in Abeta6(w302)-positive (but not in Abeta6(w302)
      negative) mice which are somatic mosaics for these genes. Biological features of
      Abeta4-7 genes make them remarkably different from the classical MHC gene system.
      All available evidence strongly suggests that these genes control
      susceptibility/resistance to the spread of metastatic tumors.

PMID- 11451416
TI  - Reevaluation of stoichiometry and affinity/avidity in interactions between anti
      hapten antibodies and mono- or multi-valent antigens.
AB  - In order to obtain further information on the interaction between antigens (Ags)
      and B cell Ag receptors (BCR) for a better understanding of the relationship
      between signals resulting from Ag binding and B cell activation, effects of Ag
      valence and size on the apparent association constant, i.e. the avidity as well
      as the molecular stoichiometry of immune complexes in Ag-antibody (Ab)
      interactions were studied. Hapten conjugates using proteins of various molecular
      weights, such as hen egg lysozyme (HEL), ovalbumin (OVA), bovine serum albumin
      (BSA), and chicken gammaglobulin (CGG), were prepared for this purpose. Different
      ratios of the hapten, (4-hydroxy-3-nitrophenyl)acetyl (NP), to the protein were
      used for conjugation, and interactions between anti-NP monoclonal Abs (mAbs) and
      the NP conjugates were evaluated by surface plasmon resonance. It was founded
      that the two binding sites of an Ab were able to simultaneously accommodate two
      NP(1)-HEL, resulting in a tri-molecular complex, Ag(2)Ab(1). However, NP
      conjugates of the higher-molecular-weight proteins, OVA and BSA, formed only
      Ag(1)Ab(1), irrespective of hapten valence. This was thought to be due to steric
      hindrance caused by the binding of the first Ag. These results suggested that the
      stoichiometry depended largely on the size of the Ag involved and that mAbs with
      a low affinity are more efficient at raising the binding strength through
      divalent interaction since the avidity of two mAbs in interactions with highly
      haptenated BSA was not significantly different in spite of a 10-fold difference
      in affinity to the monovalent NP(1)-HEL.

PMID- 11451417
TI  - Generation and characterization of a novel tetravalent bispecific antibody that
      binds to hepatitis B virus surface antigens.
AB  - Hepatitis B virus (HBV) infection is a worldwide public health problem affecting
      about 350 million people. HBV envelope contains three surface antigens, called
      pre-S1, pre-S2 and S. For the prophylaxis of HBV infection, only an anti-S
      monoclonal antibody was tested for the protective efficacy against HBV infection,
      but it was shown to be incomplete. In addition, some immune escape mutants
      carrying mutations on the S antigen were reported. Therefore, a multivalent
      bispecific antibody rather than a single monoclonal antibody would be more
      beneficial for the prophylaxis of HBV infection. We have generated a novel
      tetravalent bispecific antibody with two binding sites for each of the S and pre
      S2 antigens. Each of the antigen-binding sites was composed of a single-chain Fv
      (ScFv). The tetravalent antibody was generated by constructing a single gene
      encoding a single-chain protein. This protein consisted of an anti-S ScFv whose
      carboxyl end was tethered, through a 45 amino acid linker, to the amino terminus
      of anti-preS2 ScFv that in turn was joined to the hinge region of human gamma1
      constant region. The single-chain protein was expressed in Chinese hamster ovary
      cells and secreted in culture supernatant as a homodimeric molecule. The
      tetravalent bispecific antibody showed both anti-S and anti-pre-S2 binding
      activities. In addition, the binding affinity of the bispecific antiboy for HBV
      particles was greater than that of either parental antibody. The tetravalent
      bispecific antibody is a potentially useful reagent for the prevention and
      treatment of HBV infection.

PMID- 11451418
TI  - V(D)J rearrangement in Nijmegen breakage syndrome.
AB  - Repair of DNA double-strand breaks is essential for maintenance of genomic
      stability, and is specifically required for rearrangement of immunoglobulin (Ig)
      and T cell receptor (TCR) loci during development of the immune system.
      Abnormalities in these repair processes also contribute to oncogenic chromosomal
      rearrangements that underlie many lymphoid malignancies. Nijmegen breakage
      syndrome (NBS) is a rare autosomal recessive condition characterized by
      immunodeficiency, radiation sensitivity, and increased predisposition to lymphoid
      cancers bearing oncogenic Ig and TCR locus translocations. NBS patients fail to
      produce nibrin, a protein required for the nuclear localization and function of a
      DNA repair complex that includes Mre11 and Rad50. Mre11 has biochemical
      properties that suggest a potential role in V(D)J recombination. We studied V(D)J
      recombination in NBS cells in vitro and in vivo, using cell lines and peripheral
      blood leukocyte DNA from NBS patients. We found that NBS cells were competent to
      rejoin signal substrates with normal efficiency and high fidelity. Coding
      substrates were similarly rejoined efficiently, and coding end structures
      appeared normal. In B cells from NBS patients, the spectrums of IgH CDR3 regions
      were diverse and normally distributed. Moreover, the lengths and composition of
      Igkappa VJ joins and IgH VDJ joins derived from NBS and normal subjects were
      indistinguishable. Our data indicate that nibrin plays no essential role in V(D)J
      recombination and is not required for the generation of an apparently diverse B
      cell repertoire.

PMID- 11451419
TI  - Role of natural and immune IgM antibodies in immune responses.
AB  - IgM antibodies constitute the major component of the natural antibodies and is
      also the first class of antibodies produced during a primary antibody response.
      The IgM-type antibodies differ from other classes of antibodies in that they are
      predominantly produced by B1 cells, in the absence of apparent stimulation by
      specific antigens. In addition, IgM antibodies are mostly encoded by germline V
      gene segments and have low affinities but broad specificites to both foreign and
      self structures. New developments regarding the function of both immune IgM
      antibodies and natural IgM antibodies will be examined here.

PMID- 11451421
TI  - Comparison of nitrate tolerance between different populations of the common frog,
      Rana temporaria.
AB  - Euthrophication-associated changes in the physical and biological environment of
      lakes and ponds are potentially a source of major stress for many aquatic
      organisms. In Scandinavia, the nitrate concentrations in lakes and ponds decrease
      towards north due to a naturally lower productivity of the habitats, but also due
      to lower supplementation of anthropogenic nitrogen. A chronic experiment using
      ecologically relevant concentrations of sodium nitrate (0-5000 micro gl(-1)) was
      used to test whether common frog (Rana temporaria L.) larvae from northern parts
      of Scandinavia are less well adapted to cope with high nitrate concentrations
      than those from the southern parts. Slight, but significant differences in
      nitrate tolerance, as measured in terms of growth rate and size at metamorphosis,
      between the two regions were found. High concentrations of nitrate reduced the
      growth rates and metamorphic size in north, but not in south. However, there was
      no clear-cut impact of high nitrate concentrations on developmental rate or on
      mortality until metamorphosis. The general lack of large effects of nitrate
      treatment on the response variables suggests that nitrates per se do not pose any
      significant threat to the development of R. temporaria tadpoles under a natural
      range of concentrations. This was confirmed in an acute test where results
      suggest that ammonia and nitrite, compounds seldom found in high concentrations
      in Fennoscandian lakes, are possibly responsible for the larger negative effects
      of "nitrate" observed in previous studies of amphibians.

PMID- 11451422
TI  - Differential survivorship among allozyme genotypes of Hyalella azteca exposed to
      cadmium, zinc or low pH.
AB  - The survival functions (SF) during acute exposures to cadmium, zinc or low pH
      were examined for amphipods exhibiting variation at three loci. Significant
      differences were observed in eight of nine locus/toxicant combinations. Two
      general types of survival curve patterns were identified when genotype-related SF
      differences were observed. In the first pattern, the survival differences between
      genotypes were immediately apparent with two SF curves separated at the beginning
      of exposure with little or no overlap. For the second pattern, both genotypes had
      similar SF for a period of time, during which the two survival curves crossed or
      overlapped. After this period, the survival probability of one genotype dropped
      sharply relative to the other. While SF was related to genotype, it was not
      related to heterozygosity. Genetic distance analysis showed that exposure to
      cadmium, zinc or low pH each resulted in directional selection, suggesting the
      potential use of genetic distance as a bioindicator.

PMID- 11451423
TI  - 7-Ethoxyresorufin O-deethylase induction in rainbow trout gill epithelium
      cultured on permeable supports: asymmetrical distribution of substrate
      metabolites.
AB  - The induction of 7-ethoxyresorufin O-deethylase (EROD) has been measured in
      cultured epithelia from rainbow trout gills. Epithelia incubated with water on
      the apical side and culture media at the basolateral side were exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (betaNF),
      benzo[k]fluoranthene (B(k)F), and 3,3',4,4',5-pentachlorobiphenyl (PCB#126) from
      the water. EROD activity was measured as the formation of resorufin from 7
      ethoxyresorufin over time in intact epithelia. The EC(50) values obtained after
      24 h of exposure (mean+/-S.D.) were for TCDD (n=9) 4.1+/-3.2x10(-11) M, for
      betaNF (n=6) 1.6+/-3.8x10(-9) M, for B(k)F (n=4) 5.4+/-3.0x10(-9) M and for
      PCB#126 (n=4) 6.15+/-10.1x10(-9) M. When assaying for EROD activity, it was found
      that the resorufin concentrations differed between the apical and the basolateral
      compartments, indicating an asymmetrical distribution of the enzymatically formed
      resorufin molecules. Generally, the resorufin concentration was highest in the
      basolateral compartment, but there were differences between epithelia obtained
      from different fish individuals. Of a total of 13 preparations 10 had the highest
      resorufin concentration in the basolateral compartment, while in three
      preparations, the resorufin was uniformly distributed or slightly higher in the
      apical compartment. The reasons for this asymmetrical distribution of substrate
      metabolites are not known, and the addition of multidrug resistance inhibitors
      (verapamil and cyclosporin A) did not alter the asymmetrical pattern. The
      transepithelial electrical resistance (TER) was also measured to diagnose the
      tightness of the epithelia. The change from culture media to experimental water
      (containing TCDD, betaNF, or DMSO as control) in the apical compartment resulted
      in a large increase in TER, followed by a decline, measured after 24 h. The
      cytochrome P450 1A (CYP1A) inducers had no effect on the TER and were judged,
      therefore, not to affect the tightness of the epithelia.

PMID- 11451424
TI  - Effect of beta-naphthoflavone and dimethylbenz[a]anthracene on apoptosis and
      HSP70 expression in juvenile channel catfish (Ictalurus punctatus) ovary.
AB  - Complex environmental mixtures such as pulp mill effluents and crude oil have
      been shown to increase ovarian cell apoptosis and affect heat shock protein (HSP)
      expression in fish. We hypothesize that polyaromatic hydrocarbons (PAH) mediate
      these effects. To test this hypothesis, we exposed juvenile channel catfish
      (Ictalurus punctatus) acutely to the aryl hydrocarbon receptor (AhR) agonists,
      beta-naphthoflavone (BNF; 75 mg/kg) or the model PAH, dimethylbenz[a]anthracene
      (DMBA; 50 mg/kg) via intraperitoneal injection. Apoptotic DNA fragmentation and
      HSP70 expression were determined in ovary and liver. Hepatic cytochrome P450 1A
      (CYP1A) was significantly induced, confirming that BNF and DMBA had distributed
      to internal organs and stimulated AhR. At 96 h post-injection, BNF and DMBA
      significantly increased apoptosis and decreased HSP70 expression in juvenile
      catfish ovaries. Although primary oocytes underwent the greatest rates of
      apoptosis compared to early or late vitellogenic follicles in all treatment
      groups, the cell type undergoing increased rates of apoptosis after BNF or DMBA
      exposure was not clear using terminal deoxynucleotidyl transferase (TdT)-mediated
      deoxyUTP nick end labeling (TUNEL). There was a significant negative relationship
      between expression of HSP70 and apoptosis in juvenile channel catfish ovaries.
      This differed from liver of these fish which did not exhibit increased apoptosis
      and instead increased hepatic HSP70 expression at 96 h post-injection. However,
      DMBA had no effect on apoptosis or HSP70 levels in more reproductively mature
      juvenile fish that were housed at a lower water temperature. This may be due to a
      developmental or temperature-dependent component to these responses. We propose
      that the decrease in ovarian HSP70 expression in response to BNF and DMBA may be
      causally related to the increase in ovarian cell apoptosis. Further experiments
      using a full time course, dose-response and methods to confirm that AhR is a
      direct mediator of these effects are required.

PMID- 11451425
TI  - Effect of iprodione, a dicarboximide fungicide, on primary cultured rainbow trout
      (Oncorhynchus mykiss) hepatocytes.
AB  - As is known from literature, iprodione, a dicarboximide fungicide, has a highly
      specific action, with a capacity to cause oxidative damage through production of
      free oxygen radicals (ROS), but it does not appear to be species selective. Since
      this substance is able to diffuse in water, evaluation of its capacity to induce
      oxidative damage in an aquatic organism such as the rainbow trout (Oncorhynchus
      mykiss) was considered of particular interest. A study was, therefore, undertaken
      to investigate the effect of iprodione on free radicals (ROS) and malondialdehyde
      (MDA) production, reduced glutathione (GSH) content and catalase activity (CAT),
      in primary cultured trout hepatocytes, following treatment with 0.2, 0.3 and 0.4
      mM concentrations for a 24-h period. The iprodione 0.3 and 0.4 mM concentrations
      increased both ROS and MDA production and decreased GSH content and CAT activity.
      These results suggest that iprodione is able to produce oxidative damage in
      primary cultured fish hepatocytes, thus confirming that its action is specific,
      but not species selective. It is also well known that ROS production in fungi is
      due to interaction with the flavin enzyme NADPH cytochrome c reductase to the
      extent that the normal electron flow from NADPH to cytochrome c is blocked. In
      contrast, we observed that, in primary cultured trout hepatocytes, iprodione
      appears to have no effect on NADPH cytochrome c reductase activity. It is,
      therefore, possible to presume that the mechanism of oxidative damage in trout
      hepatocytes differs from that observed in fungi. Moreover, our experiments also
      demonstrate that iprodione is able to induce "in vitro" CYP1A1, leading to the
      conclusion that the production of ROS is due to this phenomenon.

PMID- 11451426
TI  - Quantitative reverse transcription polymerase chain reaction of a molluscan
      metallothionein mRNA.
AB  - A quantitative assay based on competitive reverse transcription polymerase chain
      reaction (RT-PCR) was developed for metallothionein (MT) mRNA of the mollusc
      Crassostrea virginica and applied to analysis of MT mRNA of hemocytes. The assay
      was based on titration of a competitive external standard cRNA derived from the
      coding region of the oyster MT mRNA. Serial dilutions of the cRNA standard were
      coamplified with a constant amount of total RNA using biotinylated primers common
      to both target and standard sequences. Amplified products were bound to
      streptavidin-coated plates and hybridized to sequence-specific fluorescein
      labeled probes. Detection was based on single photon counting of
      chemiluminescence generated by an alkaline phosphatase-conjugated antifluorescein
      antibody. For quantification, the target chemiluminescence was normalized to that
      of the standard, and the amount of target MT mRNA in the sample was derived from
      the titration. Cadmium-induced MT mRNA equivalent to that in 180 hemocytes was
      easily detected, and, for routine quantitative analysis, was sufficiently
      sensitive to quantify basal and induced MT mRNA. Basal hemocyte MT mRNA of 133+/
      8 (1 S.E.) amol per microgram total RNA was induced 5-fold to 573+/-14 amol per
      microgram total RNA by in vitro exposure to 15 microM CdCl(2) for 20 h.

PMID- 11451427
TI  - Specific expression of cytochrome P4501A1 gene in gill, intestine and liver of
      tilapia exposed to coastal sediments.
AB  - Toxicological effects of persistent organic pollutants (POPs) in aquatic
      ecosystems lead to the deterioration of water quality and adversely affect fish
      and human health. The highly lipophilic nature of these pollutants may enter fish
      through the diet or by water-borne exposure. In monitoring contamination in
      aquatic systems, induction of the cytochrome P450 1A1 (CYP1A1) gene of fish has
      been evaluated as a sensitive, "early warning" method. The objective of the
      present study was to characterize the induction of the gene in fish upon exposure
      to coastal sediments and to determine its specific expression in liver and
      extrahepatic organs (i.e. gill and intestine) in which the toxicological effects
      to the corresponding tissues could be addressed. Sediment samples were collected
      from different sites, including Victoria Harbour (VS), Ma Wan (MW), Tsim Bei Tsui
      (TBT) and Mai Po (MP). The samples were analyzed for polychlorinated biphenyls
      (PCBs) and polycyclic aromatic hydrocarbons (PAHs). CYP1A1 mRNA expression was
      measured in juvenile tilapia exposed experimentally to coastal sediment for 3 and
      7 days. A negative control group of fish maintained in seawater was used. Using
      the primer dropping polymerase chain reaction technique, gill, intestinal and
      hepatic CYP1A1 mRNAs were quantified. Chemical analysis shows that the samples
      from VS contaminated with the highest concentration of PCBs (45.24 p.p.b.) and
      PAHs (1663.7 p.p.b.), followed by MW (16.01 and 347.7 p.p.b.), TBT (14.48 and
      235.2 p.p.b.) and MP (14.60 and 242.2 p.p.b.). Fish exposed to sediments were
      contaminated with various levels of PCBs (VS, 64.14-72.06 p.p.b.; MP, 27.06-31.62
      p.p.b.; TBT, 27.29-33.92 p.p.b.; MW, 16.05-17.76 p.p.b.) and PAHs (VS, 124.7
      304.9 p.p.b.; MP, 97.57-164.1 p.p.b.; TBT, 25.38-98 p.p.b.; MW, 24.07-68.13
      p.p.b.). The control fish displayed moderate expression of CYP1A1 mRNA in liver
      (1.45 arbitrary units), gill (1.21 arbitrary units) and intestine (0.56 arbitrary
      units). Following sediment exposure, there was a large increase in CYP1A1 mRNA in
      intestine and liver but no significant changes in gill tissues. In the first 3
      days, there was anywhere from 34-96 and 69-156% induction of the CYP1A1
      transcripts in intestine and liver, respectively. Following 7 days of exposure, a
      continued induction of high level of CYP1A1 mRNA in intestine (73-157%) was
      observed. The induction of CYP1A1 in liver and intestine provided a defensive
      mechanism against POPs entering from the external environment.

PMID- 11451428
TI  - Examination of the behavior and liver and thyroid histology of juvenile rainbow
      trout (Oncorhynchus mykiss) exposed to high dietary concentrations of C(10)-,
      C(11)-, C(12)- and C(14)-polychlorinated n-alkanes.
AB  - Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to high dietary
      concentrations of six polychlorinated n-alkane (PCAs) (C(10)H(15.5)C(6.5),
      C(10)H(15.3)Cl(6.7),C(11)H(18.4)Cl(5.6),C(12)H(19.5)Cl(6.5),C(14)H(24.9)Cl(5.1)
      and C(14)H(23.3)Cl(6.7)) for 21 to assess their effects on behavior and liver and
      thyroid histology and for 85 days to assess histology for a longer term exposure.
      This is the first histological work using PCAs of known carbon chain length and
      chlorine content and the first effort to examine the histopathology of fish
      exposed to PCAs. PCAs, also known as chlorinated paraffins, are complex
      industrial products for which there is a lack of toxicological data on individual
      congeners. With the exception of trout exposed to C(14)H(24.9)Cl(5.1), which had
      much lower exposure concentrations, many of the trout exposed to the PCAs (whole
      fish concentrations 0.22-5.5 microg g(-1)) showed a diminished or no startle
      response, loss of equilibrium, and developed a dark coloration. These responses
      are indicative of a narcotic toxicological mode-of-action. Histopathological
      lesions were observed in the livers of trout from each exposure group. However,
      the most severe histopathologies were observed in the livers of fish exposed to
      C(10)H(15.3)Cl(6.7) and C(11)H(18.4)Cl(5.6) (whole fish concentrations 0.92 and
      5.5 microg g(-1), respectively), in which extensive fibrous lesions were present
      that were not observed in any other exposure group. Other alterations observed in
      all treatment groups included hepatocyte necrosis, sites of inflammation, and
      glycogen/lipid depletion. The relative sizes of hepatocytes of PCA exposed trout
      were smaller than control trout, although only a few of the observed differences
      were statistically significant. No lesions were present in the thyroid, although
      trout exposed to C(10)H(15.5)Cl(6.5) (whole fish concentration 0.84 microg g(-1))
      had slightly more active thyroids, as indicated by an increased mean thyroid
      epithelium cell height relative to controls. It would appear that PCA toxicity is
      inversely related to carbon chain length, as has been observed in similar studies
      using mammals. The concentrations in the fish from this experiment were at levels
      that have been reported in invertebrates and fish from contaminated sites in the
      Great Lakes. However, the exposure concentrations were likely much greater in
      these experiments compared with the environment and require further study.

PMID- 11451429
TI  - Effect of 17beta-estradiol, o,p'-DDT, octylphenol and p,p'-DDE on gonadal
      development and liver and kidney pathology in juvenile male summer flounder
      (Paralichthys dentatus).
AB  - The intent of this study was to compare histopathologically the effect of 17beta
      estradiol (E(2)), o,p'-DDT, octylphenol and p,p'-DDE on gonadal development and
      liver and kidney condition in sexually immature (juvenile) summer flounder
      (Paralichthys dentatus). The dorsal sinus of 2-year-old juvenile male summer
      flounder was injected with the appropriate amount of chemical incorporated in
      coconut oil. A second identical injection was administered 2 weeks later. Fish
      were sampled at 4, 6 and 8 weeks after the initial injection and observed
      histopathologically. In control fish, spermatogenesis was predominantly in mid to
      late maturation. In fish treated with 1.0 and 10.0 mg/kg E(2) spermatogenesis
      regressed to primary spermatogonia or an immature functional state. Testicular
      atrophy and spermatogonial proliferation was also observed. An eosin-positive,
      hyaline material was found in the gonad, liver and kidney. This eosinophilic
      material also stained positive with Periodic Acid Schiff (PAS) stain. Treatment
      of 30 or 60 mg/kg o,p'-DDT elicited altered gonadal development similar to that
      observed with E(2) treated fish. Octylphenol treatment of 100 mg/kg resulted in
      reduced testicular size, ducts full of sperm, numerous spermatogonia and PAS
      positive material in the testis with no developing sperm cysts. No effect on
      liver or gonad tissues was observed with p,p'-DDE at the concentrations tested.
      All chemicals tested, with exception of p,p'-DDE, altered gonadal development,
      whereas only E(2) caused histopathological changes in the liver and kidney.
      Estrogenic activity induced the liver to produce a vitellogenin (VtG)-like
      substance and inhibited testicular maturation. As a result, both the lack of
      target cells for VtG and a continuous supply of VtG from the liver allowed the
      hyaline material to accumulate in the liver, testis and kidney causing
      histopathological changes.

PMID- 11451430
TI  - Effects of endosulfan and nonylphenol on the primordial germ cell population in
      pre-larval zebrafish embryos.
AB  - A variety of chemicals released into the aquatic environment are capable of
      targeting the reproductive system in fish and other vertebrates. Some of the
      effects observed in exposed adults may arise by permanent organizational changes
      that occur during embryogenesis, including changes in gonad structure and
      function. Little work has addressed the effects of pesticides and industrial
      chemicals, many of which are recognized as endocrine disrupting chemicals, on
      early embryos. The recent cloning of the vasa gene in zebrafish, the mRNA of
      which is found in fertilized eggs and is later segregated into the primordial
      germ cells (PGCs), has provided a unique opportunity to examine PGC migration and
      positioning in early embryos. We utilized antisense RNA probes to vasa mRNA in
      whole mount in situ hybridization analysis in order to examine the early
      migration and distribution of PGCs in embryos exposed to endosulfan and
      nonylphenol. The data reveal that these chemicals cause alterations in the
      distribution of PGCs along the anterior-posterior axis in 24-h-old embryos. This
      suggests that the previously reported alterations in juvenile and adult gonad
      structure of various aquatic vertebrates following exposure to pesticides and
      industrial chemicals could be related in part to alterations in early PGC
      distribution.

PMID- 11451431
TI  - In vitro response of fish and mammalian cells to complex mixtures of
      polychlorinated naphthalenes, polychlorinated biphenyls, and polycyclic aromatic
      hydrocarbons.
AB  - In vitro characterization and comparison of responses to different classes of
      biologically active compounds can increase the utility of bioassays. In this
      study, the relative potencies (REPs) of mixtures of polychlorinated naphthalenes
      (PCNs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons
      (PAHs), to induce in vitro ethoxyresorufin-O-deethylase (EROD) in PLHC-1 fish
      hepatoma cells, H4IIE wild type (H4IIE-wt) rat hepatoma cells, and recombinant
      H4IIE cells (H4IIE-EROD) were determined. The mixtures were also analyzed by in
      vitro luciferase assay with recombinant H4IIE cells (H4IIE-luc). Halowaxes 1051,
      1014, and 1013 caused significant induction in all three H4IIE assays at
      concentrations less than 10 mg/l, but did not elicit a significant response in
      the PLHC-1 assay. Based on H4IIE results, the Halowaxes were estimated to have
      relative potencies (REPs) of approximately 10(-6)-10(-8) relative to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Less than 5 mg/l of Aroclors 1242, 1248,
      1254; Clophens A60, T64; and Chlorofen induced significant responses in the H4IIE
      assays, while only Clophens A60 and T64 caused a significant response in the PLHC
      1 assay. The efficacy of the Aroclor mixtures was generally insufficient to allow
      for quantitative REP estimates, but, based on their responses in the H4IIE
      assays, Clophen A60 and Chlorofen were estimated to have REPs of approximately
      10(-6) and 10(-7), respectively. A mixture of 16 priority PAHs caused significant
      induction in all four cell types and was estimated to have a REP of approximately
      10(-4). Overall, the results of this study add to a growing database on the
      dioxin-like potency of complex mixtures of xenobiotics, and suggested that H4IIE
      based in vitro bioassays were more sensitive than PLHC-1 cells for detecting
      dioxin-like activity in complex mixtures.

PMID- 11451432
TI  - Inhibition of oxygen consumption by pentachlorophenol and tetrachloroguaiacol in
      rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) were exposed for 24 h to concentrations
      representing 100, 50 and 25% of the 96 h-LC50 of pentachlorophenol (PCP) or
      tetrachloroguaiacol (TCG), and their oxygen consumption, cardiac output, heart
      rate and stroke volume were measured at regular intervals. Oxygen consumption
      either remained stable at basal levels (PCP), or increased to 130% of basal
      levels (TCG) when fish were exposed to the 96 h-LC50 of each chemical. However,
      oxygen consumption decreased to about 50-60% of basal levels when fish were
      exposed to concentrations of PCP or TCG representing 50 and 25% of the 96 h-LC50.
      This decrease in oxygen consumption did not appear to affect cardiac function
      since cardiac output, heart rate and stroke volume remained stable. PCP is best
      known for its capacity to uncouple oxidative phosphorylation and increase oxygen
      consumption. However, this study showed that it can also decrease oxygen
      consumption, and that the effects of PCP and TCG on fish metabolism are similar.

PMID- 11451433
TI  - Analysis and interpretation of the action mechanism of mushroom tyrosinase on
      monophenols and diphenols generating highly unstable o-quinones.
AB  - Tyrosinase can act on monophenols because of the mixture of met- (E(m)) and oxy
      tyrosinase (E(ox)) which exists in the native form of the enzyme. The latter form
      is active on monophenols, while the former is not. However, the kinetics are
      complicated because monophenols can bind to both enzyme forms. This situation
      becomes even more complex since the products of the enzymatic reaction, the o
      quinones, are unstable and continue evolving to generate o-diphenols in the
      medium. In the case of substrates such as L-tyrosine, tyrosinase generates very
      unstable o-quinones, in which a process of cyclation and subsequent oxidation
      reduction generates o-diphenol through non-enzymatic reactions. However, the
      release of o-diphenol through the action of the enzyme on the monophenol
      contributes to the concentration of o-diphenol in the first pseudo-steady-state
      [D(0)](ss). Hence, the system reaches an initial pseudo-steady state when t-->0
      and undergoes a transition phase (lag period) until a final steady state is
      reached when the concentration of o-diphenol in the medium reaches the
      concentration of the final steady state [D(f)](ss). These results can be
      explained by taking into account the kinetic and structural mechanism of the
      enzyme. In this, tyrosinase hydroxylates the monophenols to o-diphenols,
      generating an intermediate, E(m)D, which may oxidise the o-diphenol or release it
      directly to the medium. We surmise that the intermediate generated during the
      action of E(ox) on monophenols, E(m)D, has axial and equatorial bonds between the
      o-diphenol and copper atoms of the active site. Since the orbitals are not
      coplanar, the concerted oxidation-reduction reaction cannot occur. Instead, a
      bond, probably that of C-4, is broken to achieve coplanarity, producing a more
      labile intermediate that will then release the o-diphenol to the medium or
      reunite it diaxially, involving oxidation to o-quinone. The non-enzymatic
      evolution of the o-quinone would generate the o-diphenol ([D(f)](ss)) necessary
      for the final steady state to be reached after the lag period.

PMID- 11451434
TI  - Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha
      tocopherol derivatives.
AB  - alpha-Tocopherol inhibits glutathione S-transferase P1-1 (GST P1-1) (R.I.M. van
      Haaften, C.T.A. Evelo, G.R.M.M. Haenen, A. Bast, Biochem. Biophys. Res. Commun.
      280 (2001)). In various cosmetic and dietary products alpha-tocopherol is added
      as a tocopherol ester. Therefore we have studied the effect of various tocopherol
      derivatives on GST P1-1 activity. It was found that GST P1-1 is inhibited, in a
      concentration dependent manner, by these compounds. Of the compounds tested, the
      tocopherols were the most potent inhibitors of GST P1-1; the concentration giving
      50% inhibition (IC(50)) is <1 microM. The esterified tocopherols and alpha
      tocopherol quinone also inhibit the GST P1-1 activity at a very low
      concentration: for most compounds the IC(50) was below 10 microM. RRR-alpha
      Tocopherol acetate lowered the V(max) values, but did not affect the K(m) for
      either 1-chloro-2,4-dinitrobenzene or GSH. This indicates that the GST P1-1
      enzyme is non-competitively inhibited by RRR-alpha-tocopherol acetate. The
      potential implications of GST P1-1 inhibition by tocopherol and alpha-tocopherol
      derivatives are discussed.

PMID- 11451435
TI  - Trifluoroethanol-assisted protein folding: fragment 53--103 of bovine alpha
      lactalbumin.
AB  - Fragment 53--103 of bovine alpha-lactalbumin, prepared by limited peptic
      digestion of the protein at low pH, is a 51-residue polypeptide chain crosslinked
      by two disulfide bonds encompassing helix C (residues 86--98) of the native
      protein. Refolding of the fully reduced fragment (four--SH groups) is expected to
      lead to three fully oxidized isomers, the native (61--77, 73--91) and the two
      misfolded species named ribbon (61--91, 73--77) and beads (61--73, 77--91)
      isomers. The fragment with correct disulfide bonds was formed in approx. 30%
      yield when refolding was conducted in aqueous solution at neutral pH in the
      presence of the redox system constituted by reduced and oxidized glutathione. On
      the other hand, when the reaction was conducted in 30% (v/v) trifluoroethanol
      (TFE), the oxidative refolding to the native isomer was almost quantitative. To
      provide an explanation of the beneficial effect of TFE in promoting the correct
      oxidative folding, the conformational features of the various fragment species
      were analyzed by far-UV circular dichroism measurements. The fully reduced
      fragment is largely unfolded in water, but it becomes helical in aqueous TFE.
      Correctly refolded fragment is produced most when the helical contents of the
      reduced and oxidized fragment in aqueous TFE are roughly equal. It is proposed
      that 30% TFE promotes a native-like format of the fragment and thus an efficient
      and correct pairing of disulfides. Higher concentrations of TFE, instead, promote
      some non-native helical secondary structure in the fragment species, thus
      hampering correct folding.

PMID- 11451436
TI  - Modification of a single tryptophan residue in human Cu,Zn-superoxide dismutase
      by peroxynitrite in the presence of bicarbonate.
AB  - Human recombinant Cu,Zn-SOD was reacted with peroxynitrite in a reaction mixture
      containing 150 mM potassium phosphate buffer (pH 7.4) 25 mM sodium bicarbonate,
      and 0.1 mM diethylenetriamine pentaacetic acid. Disappearance of fluorescence
      emission at 350 nm, which could be attributed to modification of a single
      tryptophan residue, was observed in the modified enzyme with a pH optimum of
      around 8.4. A fluorescence decrease with the same pH optimum was also observed
      without sodium bicarbonate, but with less efficiency. Amino acid contents of the
      modified enzyme showed no significant difference in all amino acids except the
      loss of a single tryptophan residue of the enzyme. The peroxynitrite-modified
      enzyme showed an increase in optical absorption around 350 nm and 30% reduced
      enzyme activity based on the copper contents. The modified enzyme showed the same
      electron paramagnetic resonance spectrum as that of the control enzyme. The
      modified Cu,Zn-SOD showed a single protein band in sodium dodecyl sulfate-
      polyacrylamide gel electrophoresis (SDS--PAGE) and five protein bands in non
      denaturing PAGE. From this evidence, we conclude that nitration and/or oxidation
      of the single tryptophan 32 and partial inactivation of the enzyme activity of
      Cu,Zn-SOD is caused by a peroxynitrite-carbon dioxide adduct without perturbation
      of the active site copper integrity.

PMID- 11451437
TI  - Studies on the function of yeast protein disulfide isomerase in renaturation of
      proteins.
AB  - Renaturation of two enzymes lacking disulfide bonds, citrate synthase (CS), and
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and another protein containing
      disulfide bonds, lysozyme (LZM), were studied in order to dissect the possible
      chaperone function from the isomerase function of yeast protein disulfide
      isomerase (PDI). Our findings suggest no independent chaperone activity of yeast
      PDI with respect to the two enzymes lacking disulfide bonds, GAPDH and CS, since
      neither of these enzymes required PDI for renaturation. In contrast, a high level
      of renaturation of LZM was observed in the presence of PDI. Renaturation of LZM
      involved formation and rearrangement of disulfide bonds. Additional studies using
      LZM as a substrate were done to examine the role of cysteine residues in the two
      active sites of PDI. Studies with a series of cysteine to serine mutants and
      truncation mutants of yeast PDI revealed that the two active sites of PDI were
      not equal in activity. An intramolecular disulfide bond in at least one active
      site of PDI was required for the oxidation of reduced LZM. The first cysteine in
      each active site was necessary for disulfide bond rearrangement, i.e.,
      isomerization, in LZM, while the second cysteine was not.

PMID- 11451438
TI  - Purification and characterisation of a haemorrhagic fraction from the venom of
      the Uracoan rattlesnake Crotalus vegrandis.
AB  - Uracoan rattlesnake (Crotalus vegrandis) venom was subjected to chromatographic,
      electrophoretic, biochemical and in vivo haemorrhagic analysis. A haemorrhagic
      toxin (Uracoina-1) active on skin at the site of inoculation in mice was purified
      by Mono Q2 anion-exchange chromatography and size exclusion (SE) high-performance
      liquid chromatography. The purified preparation was a protein of M(r) 58,000 as
      revealed by sodium dodecyl sulphate--polyacrylamide gel electrophoresis under
      denatured conditions and with silver staining. The use of EDTA, EGTA and 1,10
      phenanthroline inhibited haemorrhagic and proteolytic activities. Inhibitors of
      serine proteinases such as PMSF and TCLK had no effect on the haemorrhagic
      fraction. Uracoina-1 hydrolyses casein, hide powder azure and fibrinogen have an
      optimal pH of 8.2. It rapidly digests the A alpha-chain of fibrinogen. Thermal
      denaturation of Uracoina-1 after exposure at 60 degrees C for 15 min led to
      inactivation of the haemorrhagic activity. In addition, Uracoina-1 is myotoxic,
      lacking haemolytic, defibrinating and lethal effects. The N-terminal amino acid
      sequence (20 residues) was determined.

PMID- 11451439
TI  - AMP inhibition of pig kidney fructose-1,6-bisphosphatase.
AB  - Lys-112 and Tyr-113 in pig kidney fructose-1,6-bisphosphatase (FBPase) make
      direct interactions with AMP in the allosteric binding site. Both residues
      interact with the phosphate moiety of AMP while Tyr-113 also interacts with the
      3'-hydroxyl of the ribose ring. The role of these two residues in AMP binding and
      allosteric inhibition was investigated. Site-specific mutagenesis was used to
      convert Lys-112 to glutamine (K112Q) and Tyr-113 to phenylalanine (Y113F). These
      amino acid substitutions result in small alterations in k(cat) and increases in
      K(m). However, both the K112Q and Y113F enzymes show alterations in Mg(2+)
      affinity and dramatic reductions in AMP affinity. For both mutant enzymes, the
      AMP concentration required to reduced the enzyme activity by one-half,
      [AMP](0.5), was increased more than a 1000-fold as compared to the wild-type
      enzyme. The K112Q enzyme also showed a 10-fold reduction in affinity for Mg(2+).
      Although the allosteric site is approximately 28 A from the metal binding sites,
      which comprise part of the active site, these site-specific mutations in the AMP
      site influence metal binding and suggest a direct connection between the
      allosteric and the active sites.

PMID- 11451440
TI  - Kringles of the plasminogen--prothrombin gene family share conformational
      epitopes with recombinant apolipoprotein (a): specificity of the fibrin-binding
      site.
AB  - Monoclonal antibodies directed against recombinant apolipoprotein (a) (r-apo(a))
      lacking plasminogen-like KIV-2 repeats were used to identify structurally related
      conformational epitopes in various members of the plasminogen-prothrombin gene
      family. A number of procedures including a fibrin-binding inhibition immunoassay
      and surface plasmon resonance studies were used. Two antibodies (A10.1 and A10.4)
      recognised common conformational structures in r-apo(a), prothrombin, factor XII,
      plasminogen and its tissue-type and urokinase-type activators. In contrast, two
      other antibodies recognised specifically an epitope comprising residues of the
      lysine-binding site (A10.2) or close to it (A10.5) and inhibited the fibrin
      binding function of r-apo(a) (IC(50)=36 pmol/l and 9.76 nmol/l, respectively).
      Interestingly, these antibodies distinctly recognised the elastase-derived
      fragments of plasminogen K4 (A10.2) and K1+2+3 (A10.5) without affecting
      plasminogen binding to fibrin. These results suggest that highly conserved
      conformational regions are common to various proteins of the plasminogen
      prothrombin gene family and are in agreement with the concept that these proteins
      constitute a monophyletic group derived from an ancestral gene.

PMID- 11451441
TI  - Structure of the YSPTSPS repeat containing two SPXX motifs in the CTD of RNA
      polymerase II: NMR studies of cyclic model peptides reveal that the SPTS turn is
      more stable than SPSY in water.
AB  - The carboxyl-terminal domain of RNA polymerase II, which is rich in
      phosphorylation sites, contains 17--52 tandem repeats with the consensus sequence
      of the heptapeptide, YSPTSPS. The repeat unit of the heptapeptide has two SPXX
      motifs showing potential beta-turns, SPTS and SPSY. NMR studies were performed in
      water at pH 4.0 for two cyclic peptides containing one and two repeat units,
      cyclo-[C(1)R(2)D(3)Y(4)S(5)P(6)T(7)S(8)P(9)S(10)Y(11)S(12)R(13)D(14)C(15)]
      (peptide 1) and cyclo
      [C(1)R(2)D(3)Y(4)S(5)P(6)T(7)S(8)P(9)S(10)Y(11)S(12)P(13)T(14)S(15)P(16)N(17)Y(18
      S(19)R(20)D(21)C(22)] (peptide 2), which are cyclized with a disulfide bridge of
      two Cys residues at the N- and C-termini. SP in 1 and 2 are predominantly in
      trans form. The following NMR parameters were detected: (1) lower temperature
      coefficients of amide proton chemical shifts of T7 and S8 in 1, and Tx (T7 or
      T14), Sx (S8 or S15), Tz (T14 or T7) and Sz (S15 or S8) in 2, (2) significantly
      large deviation of H(alpha) chemical shifts from its random coil value (Delta
      H(alpha)) of Pro preceding the Thr (P6 in 1, and Px and Pz in 2), (3) relatively
      large (3)J(HNH alpha) coupling constants (>8.7 Hz) of T7 in 1 and Tx and Tz in 2,
      and (4) NOE (d(NN) (i, i+1)) connectivities between the amide protons of T7-S8
      and S10-Y11 in 1, and Tx-Sx, S10-Y11, Tz-Sz, and N17-Y18 in 2, although two Pro
      Thr-Ser segments in 2 (each of these are annotated by 'x' and 'z') in the first
      and second repeat units were not distinguishable. Comparison of the NMR
      parameters between the cyclic peptides and the corresponding linear peptides
      indicates that cyclization promotes structural stabilization in water. The
      present NMR data were consistent with the presence of a beta-turn at both SPTS
      and SPSY: S(5)P(6)T(7)S(8) and S(8)P(9)S(10)Y(11) in 1, and SPxTxSx, SPzTzSz,
      SP(9)S(10)Y(11), SP(16)N(17)Y(18) in 2. However, the structure of the SPTS
      segment is more stable than that of the SPSY segment. Conformations consistent
      with NMR parameters including NOE distances were obtained through molecular
      dynamics and energy minimization methods. These calculations yielded two stable
      conformers for the SPTS segment. One of the two corresponds to a type I beta
      turn.

PMID- 11451442
TI  - Isozymes of Ipomoea batatas catechol oxidase differ in catalase-like activity.
AB  - The amino acid sequences of two isozymes of catechol oxidase from sweet potatoes
      (Ipomoea batatas) were determined by Edman degradation of BrCN cleavage fragments
      of the native protein and by sequencing of amplified cDNA fragments. Sequence
      alignment and phylogenetic analysis of plant catechol oxidases revealed about 80%
      equidistance between the two I. batatas catechol oxidases and approximately 40-
      60% to catechol oxidases of other plants. When H(2)O(2) was applied as substrate
      the 39 kDa isozyme, but not the 40 kDa isozyme, showed catalase-like activity.
      The structure of the 40 kDa isozyme was modeled on the basis of the published
      crystal structure of the 39 kDa isozyme [T. Klabunde et al., Nat. Struct. Biol. 5
      (1998) 1084]. The active site model closely resembled that of the 39 kDa isozyme
      determined by crystallography, except for a mutation of Thr243 (40 kDa isozyme)
      to Ile241 (39 kDa isozyme) close to the dimetal center. This residue difference
      affects the orientation of the Glu238/236 residue, which is thought to be
      responsible for the catalase-like activity of the 39 kDa isozyme for which a
      catalytic mechanism is proposed.

PMID- 11451443
TI  - A calorimetric study of the binding of S-alkylglutathiones to glutathione S
      transferase.
AB  - The binding of three competitive glutathione analogue inhibitors (S
      alkylglutathione derivatives) to glutathione S-transferase from Schistosoma
      japonicum, SjGST, has been investigated by isothermal titration microcalorimetry
      at pH 6.5 over a temperature range of 15--30 degrees C. Calorimetric measurements
      in various buffer systems with different ionization heats suggest that no protons
      are exchanged during the binding of S-alkylglutathione derivatives. Thus, at pH
      6.5, the protons released during the binding of substrate may be from its thiol
      group. Calorimetric analyses show that S-methyl-, S-butyl-, and S
      octylglutathione bind to two equal and independent sites in the dimer of SjGST.
      The affinity of these inhibitors to SjGST is greater as the number of methylene
      groups in the hydrocarbon side chain increases. In all cases studied, Delta G(0)
      remains invariant as a function of temperature, while Delta H(b) and Delta S(0)
      both decrease as the temperature increases. The binding of three S
      alkylglutathione derivatives to the enzyme is enthalpically favourable at all
      temperatures studied. The temperature dependence of the enthalpy change yields
      negative heat capacity changes, which become less negative as the length of the
      side chain increases.

PMID- 11451444
TI  - Stabilization of pancreatic ribonuclease A by immobilization on Sepharose-linked
      antibodies that recognize the labile region of the enzyme.
AB  - The stabilizing potential of the antibodies recognizing the labile region of
      pancreatic ribonuclease A (RNase) has been investigated. The dodecapeptide
      SRNLTKDRAKPV corresponding to the labile region 32--43 on RNase was synthesized
      by the solid-phase method. Antiserum raised against the dodecapeptide-bovine
      serum albumin conjugate showed good cross-reactivity with the peptide and native
      RNase. RNase immobilized on Sepharose support precoupled either with the
      antipeptide immunoglobulin (IgG) or anti-RNase IgG proved to be more resistant to
      thermal inactivation than the soluble enzyme. Besides, stability against
      inactivation by trypsin at 55 degrees C was markedly high when enzyme was
      immobilized on the antipeptide IgG support, as compared to the soluble and other
      immobilized preparations. These results suggest that matrices bearing antibodies
      recognizing specific labile regions of enzyme may be useful in selectively
      improving their stability against specific forms of inactivation.

PMID- 11451445
TI  - Spectral and kinetic studies on eosinophil peroxidase compounds I and II and
      their reaction with ascorbate and tyrosine.
AB  - Eosinophil peroxidase, the major granule protein in eosinophils, is the least
      studied human peroxidase. Here, we have performed spectral and kinetic
      measurements to study the nature of eosinophil peroxidase intermediates,
      compounds I and II, and their reduction by the endogenous one-electron donors
      ascorbate and tyrosine using the sequential-mixing stopped-flow technique. We
      demonstrate that the peroxidase cycle of eosinophil peroxidase involves a
      ferryl/porphyrin radical compound I and a ferryl compound II. In the absence of
      electron donors, compound I is shown to be transformed to a species with a
      compound II-like spectrum. In the presence of ascorbate or tyrosine compound I is
      reduced to compound II with a second-order rate constant of (1.0+/-0.2)x10(6) M(
      1) s(-1) and (3.5+/-0.2)x10(5) M(-1) s(-1), respectively (pH 7.0, 15 degrees C).
      Compound II is then reduced by ascorbate and tyrosine to native enzyme with a
      second-order rate constant of (6.7+/-0.06)x10(3) M(-1) s(-1) and (2.7+/
      0.06)x10(4) M(-1) s(-1), respectively. This study revealed that eosinophil
      peroxidase compounds I and II are able to react with tyrosine and ascorbate via
      one-electron oxidations and therefore generate monodehydroascorbate and tyrosyl
      radicals. The relatively fast rates of the compound I reduction demonstrate that
      these reactions may take place in vivo and are physiologically relevant.

PMID- 11451446
TI  - Interactions of atrazine and 2,4-D with human serum albumin studied by gel and
      capillary electrophoresis, and FTIR spectroscopy.
AB  - The herbicides 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine
      (atrazine) and 2,4-dichlorophenoxyacetic acid (2,4-D) are widely used in
      agricultural practice to fight dicotyledon weeds mainly in maize, cereals, and
      lucerne. As a result, these compounds are found not only in the plants, soil, and
      water, but also in the cultivated ground in the following years as well as in
      agricultural products such as fruits, milk, butter, and sugar beet. The
      toxicological effects of herbicides occur in vivo, when transported to the target
      organ through the bloodstream. It has been suggested that human serum albumin
      (HSA) serves as a carrier protein to transport 2,4-D to molecular targets. This
      study was designed to examine the interaction of atrazine and 2,4-D with HSA in
      aqueous solution at physiological pH with herbicide concentrations of 0.0001-1
      mM, and final protein concentration of 1% w/v. Gel and capillary electrophoresis,
      UV-visible and Fourier transform infrared spectroscopic methods were used to
      determine the drug binding mode, the drug binding constant, and the protein
      secondary structure in aqueous solution. Structural analysis showed that
      different types of herbicide-HSA complexes are formed with stoichiometric ratios
      (drug/protein) of 3:1 and 11:1 for atrazine and 4.5:1 and 10:1 for 2,4-D
      complexes. Atrazine showed a weak binding affinity (K=3.50 x 10(4) M(-1)),
      whereas two bindings (K(1)=2.50 x 10(4) M(-1) and K(2)=8.0 x 10(3) M(-1)) were
      observed for 2,4-D complexes. The herbicide binding results in major protein
      secondary structural changes from that of the alpha-helix 55% to 45--39% and beta
      sheet 22% to 24--32%, beta-anti 12% to 10--22% and turn 11% to 12--15%, in the
      drug-HSA complexes. The observed spectral changes indicate a partial unfolding of
      the protein structure, in the presence of herbicides in aqueous solution.

PMID- 11451447
TI  - A constitutively active pituitary adenylate cyclase activating polypeptide
      (PACAP) type I receptor shows enhanced photoaffinity labeling of its highly
      glycosylated form.
AB  - In the present study, we have analyzed a previously identified constitutively
      active pituitary adenylate cyclase activating polypeptide (PACAP) type I (PAC1)
      receptor with a deletion of the single amino acid residue Glu(261) (Y.-J. Cao, G.
      Gimpl, F. Fahrenholz, A mutation of second intracellular loop of pituitary
      adenylate cyclase activating polypeptide type I receptor confers constitutive
      receptor activation, FEBS Lett. 469 (2000)). This glutamic acid residue is highly
      conserved within the second intracellular loop of class II G protein-coupled
      receptors and may thus be of importance for many members of this receptor class.
      To explore the molecular characteristics of this mutant receptor, we performed
      photoaffinity labeling using previously defined photoreactive PACAP analogues. In
      COS cells, the PAC1 receptor was expressed in two differently glycosylated forms:
      a M(r) 75,000 and a M(r) 55,000 form. According to partial deglycosylation, at
      least three carbohydrate chains may exist in the rat PAC1 receptor expressed in
      COS cells. The constitutively active PAC1 receptor was expressed at the surface
      of COS-7 cells at the same density as the wild-type receptor. With respect to the
      different photoreactive PACAP analogues, the labeling specificity was the same
      for the wild-type versus mutant receptor: (125)I-[Lys(15)(pBz(2))]-PACAP-27 and
      (125)I-[Bpa(22)]-PACAP-27 were efficiently incorporated into each of the
      receptors, whereas (125)I-[Bpa(6)]-PACAP-27 labeled each of the receptors only to
      a negligible extent. This suggests that both receptors have the same or at least
      a very similar hormone binding site which is in close contact to Tyr(22) and
      Lys(15) located in the carboxy-terminal alpha-helical region of the PACAP-27
      molecule. However, in comparison with the wild-type PAC1 receptor, the
      constitutively active receptor showed a markedly (approx. 6--8-fold) enhanced
      photoaffinity labeling efficiency in particular of the high glycosylated form.
      The enzymatically deglycosylated rat PAC1 receptor was efficiently labeled by
      photoreactive PACAP analogues. In contrast, nonglycosylated PAC1 receptors
      produced by tunicamycin treatment of the transfected COS-7 cells showed a 30-fold
      lower affinity for PACAP-27 and were capable of signal transduction with 30--50
      fold lower potency as compared with the glycosylated PAC1 receptors.

PMID- 11451448
TI  - Crystal structure of alpha-momorcharin in 80% acetonitrile--water mixture.
AB  - Crystals of alpha-momorcharin (MMC) were cross-linked and soaked in an 80%
      acetonitrile--water mixture and X-ray data were collected to 2.2 A resolution.
      MMC is a ribosome-inactivating protein with a sugar chain on Asn-227. In previous
      studies, the whole conformation of the sugar chain could not be obtained in the
      aqueous system. Here the structure of MMC in a low water system is shown to be
      similar to the native one, but the sugar chain on Asn-227 is defined by the
      electron density map. Several oxygen atoms of the oligosaccharide formed
      intramolecular hydrogen bonds to the protein moiety. The conformation of the
      residues in the active center is similar to that in the aqueous system. Our
      results show conformational alteration of the tetrasaccharide of MMC in organic
      media. They indicate that the oligosaccharides are more rigid in organic
      solvents. X-ray determination in organic media may be used to solve some
      structures of oligosaccharides linked to glycoproteins.

PMID- 11451449
TI  - Factor VIIIa cofactor activity shows enhanced ionic strength sensitivity in the
      absence of phospholipid.
AB  - Factor VIIIa, a cofactor for the protease factor IXa, is a trimer of A1, A2 and
      A3-C1-C2 subunits. In the absence of phospholipid (PL), the k(cat) for factor
      VIIIa-dependent, factor IXa-catalyzed conversion of factor X was markedly less
      than that observed in the presence of PL (approx. 150 min(-1)) and decreased as
      the ionic strength of the reaction increased. At low salt concentration, the
      k(cat) (5.5 min(-1)) was approx. 8-fold greater than observed at near physiologic
      ionic strength (0.7 min(-1)). However, this level of salt showed minimal effects
      on the intermolecular affinities of factor VIIIa (or isolated A2 subunit) for
      factor IXa or on the K(m) for factor X. Alternatively, the association of A2
      subunit with A1 subunit was sensitive to increases in salt and paralleled the
      reduction in k(cat) observed with factor VIIIa. This instability was not observed
      in PL-containing reactions. Fluorescence energy transfer between acrylodan-A2 and
      fluorescein-A1/A3-C1-C2 dimer showed a requirement for both PL and factor IXa for
      maximal association of A2 with dimer. These results indicate that in the presence
      of factor IXa, the salt-dependent dissociation of factor VIIIa subunits is
      significantly enhanced in the absence of PL, promoting a reduced k(cat) for the
      cofactor-dependent generation of factor Xa.

PMID- 11451450
TI  - The first examples of (S)-2-hydroxyacid dehydrogenases catalyzing the transfer of
      the pro-4S hydrogen of NADH are found in the archaea.
AB  - Reduction of 2-oxoacids to the corresponding (S)-2-hydroxyacids is an important
      transformation in biochemistry. To date all (S)-2-hydroxyacid dehydrogenases
      belonging to the L-lactate/L-malate dehydrogenase family have been found to
      transfer the pro-4R hydrogen of either NADH or NADPH to C-2 of the 2-oxoacid
      substrates during their reduction. Here, we report that recombinantly generated
      (S)-2-hydroxyacid dehydrogenases present in the methanoarchaea Methanococcus
      jannaschii and Methanothermus fervidus use the pro-4S hydrogen of NADH to reduce
      a series of 2-oxoacids to the corresponding (S)-2-hydroxyacids. This information
      as well as the low sequence identity between these archaeal enzymes and the L
      lactate/L-malate family of enzymes indicate that these enzymes are not
      evolutionary related and therefore constitute a new class of (S)-2-hydroxyacid
      dehydrogenases.

PMID- 11451451
TI  - A new era in pyrogen testing.

PMID- 11451468
TI  - AIDS on the decrease?

PMID- 11451470
TI  - Industrial-scale, genomics-based drug design and discovery.
AB  - The demands on drug discovery organizations have increased dramatically in recent
      years, partly because of the need to identify novel targets that are both
      relevant to disease and chemically tractable. This is leading to an industrial
      approach to traditional biology and chemistry, inspired in part by the revolution
      in genomics. The purpose of this article is to highlight the flow of
      investigation from gene sequence of potential therapeutic targets, through mRNA
      and protein expression, to protein structure and drug design. To deal with this
      scale of activity, many commercial and public organizations have been established
      and some of the key players will be listed in this article.

PMID- 11451471
TI  - Immunomodulators and delivery systems for vaccination by mucosal routes.
AB  - Current paediatric immunization programmes include too many injections in the
      first months of life. Oral or nasal vaccine delivery eliminates the requirement
      for needles and can induce immunity at the site of infection. However, protein
      antigens are poorly immunogenic when so delivered and can induce tolerance. Novel
      ways to enhance immune responses to protein or polysaccharide antigens have
      opened up new possibilities for the design of effective mucosal vaccines. Here,
      we discuss the immunological principles underlying mucosal vaccine development
      and review the application of immunomodulatory molecules and delivery systems to
      the selective enhancement of protective immune responses at mucosal surfaces.

PMID- 11451472
TI  - Detection of physiologically active compounds using cell-based biosensors.
AB  - Cell-based biosensors are portable devices that contain living biological cells
      that monitor physiological changes induced by exposure to environmental
      perturbations such as toxicants, pathogens or other agents. Methods of detecting
      physiological changes include extracellular electrical recordings, optical
      measurements, and, in the future, functional genomics and proteomics. Several
      technical developments are occurring that will increase the feasibility of cell
      based biosensors for field applications; these developments include stem cell and
      3D culture technologies. Possible scenarios for the use of cell-based biosensors
      include broad-range detectors of unknown threat agents and functional assessment
      of identified agents.

PMID- 11451473
TI  - Molecular properties in cell adhesion: a physical and engineering perspective.
AB  - The past several years have seen accelerating growth in research directed towards
      the understanding and control of cell adhesion processes, from a spectrum of
      disciplinary approaches including molecular cell biology, biochemistry,
      biophysics and bioengineering. Consequently, our understanding of the mechanisms
      involved in cell adhesion has increased substantially. Corresponding quantitative
      analysis and modeling of the key molecular properties governing their action in
      regulating dynamic cell attachment and detachment events is crucial for advancing
      conceptual insight along with technological applications.

PMID- 11451474
TI  - Whole-cell biocomputing.
AB  - The ability to manipulate systems on the molecular scale naturally leads to
      speculation about the rational design of molecular-scale machines. Cells might be
      the ultimate molecular-scale machines and our ability to engineer them is
      relatively advanced when compared with our ability to control the synthesis and
      direct the assembly of man-made materials. Indeed, engineered whole cells
      deployed in biosensors can be considered one of the practical successes of
      molecular-scale devices. However, these devices explore only a small portion of
      cellular functionality. Individual cells or self-organized groups of cells
      perform extremely complex functions that include sensing, communication,
      navigation, cooperation and even fabrication of synthetic nanoscopic materials.
      In natural systems, these capabilities are controlled by complex genetic
      regulatory circuits, which are only partially understood and not readily
      accessible for use in engineered systems. Here, we focus on efforts to mimic the
      functionality of man-made information-processing systems within whole cells.

PMID- 11451475
TI  - Profile: Toshio Yanagida. Interview by Julie Clayton.

PMID- 11451476
TI  - Autonomic and EEG patterns distinguish transcending from other experiences during
      Transcendental Meditation practice.
AB  - This study compared EEG and autonomic patterns during transcending to "other"
      experiences during Transcendental Meditation (TM) practice. To correlate specific
      meditation experiences with physiological measures, the experimenter rang a bell
      three times during the TM session. Subjects categorized their experiences around
      each bell ring. Transcending, in comparison to "other" experiences during TM
      practice, was marked by: (1) significantly lower breath rates; (2) higher
      respiratory sinus arrhythmia amplitudes; (3) higher EEG alpha amplitude; and (4)
      higher alpha coherence. In addition, skin conductance responses to the
      experimenter-initiated bell rings were larger during transcending. These findings
      suggest that monitoring patterns of physiological variables may index dynamically
      changing inner experiences during meditation practice. This could allow a more
      precise investigation into the nature of meditation experiences and a more
      accurate comparison of meditation states with other eyes-closed conditions.

PMID- 11451477
TI  - Event-related brain potentials differentiate positive and negative mood
      adjectives during both supraliminal and subliminal visual processing.
AB  - This experiment provides brain event-related potential (ERP) evidence for
      differential processing of visually presented pleasant and unpleasant affectively
      valent words (mood adjectives) for both supraliminal (40 ms) and subliminal
      (unmasked, 1 ms) stimulus durations. Unpleasant words elicited a more positive
      amplitude than pleasant words in both durations. ERP components (P1, N1, P2, P3,
      and a late positive potential; LP) were measured at six electrode sites (F3, F4,
      P3, P4, CzPz, Oz). ERPs to subliminal stimuli demonstrated differences between
      pleasant and unpleasant words in the left hemisphere across all measured
      components. Supraliminal processing showed similar differences in the left
      hemisphere for early components (P1 and N1), but bilateral differences for late
      components (P3 and LP). Activity in the P2 time window was associated with the
      divergence between supraliminal and subliminal affective responses. Implications
      for the study of affect and consciousness are discussed.

PMID- 11451478
TI  - Cortical connectivity during word association search.
AB  - Cortical connectivity was studied in tasks of generating the use of words in
      comparison with reading aloud the same words. These tasks were used earlier in
      PET and high density ERP recordings studies (Posner and Raichle, 1997; Abdullaev
      and Posner, 1998), in which both the functional anatomy and the time course of
      cortical areas involved in word processing were described. The wavelet transforms
      of ERP records and the calculation of correlations between wavelet curves were
      used to reveal connections between cortical areas. Three stages of intracortical
      communications while task performance were found. These were: (1) the connections
      between right and left frontal and central areas which preceded stimulus delivery
      and persisted up to 180 ms after it; (2) the network connecting right and left
      frontal with left posterior temporal-parietal junction at 280-450 ms; and (3)
      communications between left and right temporal zones in 550-800 ms. The data are
      in good agreement with results of previous PET and ERP studies and supply the
      earlier findings with circuitry of cortical information transfer.

PMID- 11451479
TI  - Cellular and humoral immunity, mood and exam stress: the influences of self
      hypnosis and personality predictors.
AB  - The effects of self-hypnosis training on immune function and mood were examined
      in medical students at exam time. Hypnosis involved relaxation and imagery
      directed at improved immune function and increased energy, alertness and
      concentration. Hypotheses were made about activated and withdrawn personality
      differences. Eight high and eight low hypnotically susceptible participants were
      given 10 sessions of hypnosis, one live and nine tape-recorded, and were compared
      with control subjects (N=12). CD3, CD4, CD8, CD19 and CD56 NK cells and blood
      cortisol were assayed. Life-style, activated vs. withdrawn temperament, arousal
      and anxiety questionnaires were administered. Self-hypnosis buffered the decline
      found in controls in NK (P<0.002) and CD8 cells (P<0.0.07) and CD8/CD4% (P<0.06)
      (45-35% order of magnitude differences) while there was an increase in cortisol
      (P<0.05). The change in NK cell counts correlated positively with changes in both
      CD8 cells and cortisol. Results were independent of changes in life-style. Energy
      ratings were higher after hypnosis (P<0.01), and increased calmness with hypnosis
      correlated with an increase in CD4 counts (P<0.01). The activated temperament,
      notably the cognitive subscale (speaking and thinking quickly), was predictive of
      exam levels of T and B lymphocytes (P&z.Lt;0.08-P<0.02), and reaching r=0.72
      (P<0.001) in the non-intervention control group. The sizeable influences on cell
      mediated immunity achieved by a relatively brief, low cost psychological
      intervention in the face of a compelling, but routine, stress in young, healthy
      adults have implications for illness prevention and for patients with compromised
      immunity.

PMID- 11451480
TI  - Topographic distribution and developmental timecourse of auditory event-related
      potentials in two subtypes of attention-deficit hyperactivity disorder.
AB  - The effect of age on the topographic distribution of auditory event-related
      potentials (ERPs) recorded during a two-tone discrimination, or oddball, task was
      examined in two subtypes of attention deficit/hyperactivity disorder (AD/HD) as
      defined by the most recent diagnostic manual, DSM-IV. EEG was recorded at 17
      sites from AD/HD predominantly inattentive type (n=50) and AD/HD combined type
      (n=50) subjects aged from 8 to 17 years 11 months. ERP components were quantified
      at each site. Results revealed topographic differences from controls (n=50) that
      were common to both subtypes (e.g. target and standard P2 amplitude, and standard
      P2 latency) or unique to a particular subtype of AD/HD (Inattentive type: target
      N1, N2, P3b and standard N2 amplitude, target P2 latency; Combined type: target
      N1, P2, N2 and P3b amplitude, target N2 and standard N1 latency). These group
      differences showed different age effects. The across-region results revealed
      differing patterns of abnormal component development for each subtype, indicating
      a qualitative difference in information processing stage deficits in each of
      these AD/HD subtypes.

PMID- 11451481
TI  - Negative Strand Viruses. Proceedings of a conference. Quebec City, Canada. 24-29
      June 2000.

PMID- 11451482
TI  - Apoptosis by influenza viruses correlates with efficiency of viral mRNA
      synthesis.
AB  - A mutant influenza virus, A/NWS-Mvi, grows well in the presence of exogenous
      sialidase activity sufficient to remove all cell surface sialic acids. Related
      wild-type viruses grow very poorly under these conditions, although mutant and
      wild-type viruses bind to desialylated cells with similar efficiency and show
      similar reduction of binding to sialidase-treated cells compared to native cells.
      Here we examine entry, transcription, translation, and RNA replication and find
      that, although the viruses appear to utilize the same entry pathway, the mutant
      NWS-Mvi transcribes and replicates RNA to higher levels than the wild-type
      strains. The kinetics of replication in multi-cycle infection show that this
      enhancement of RNA synthesis facilitates growth where entry is restricted. The
      hemagglutinin (HA) protein of NWS-Mvi lyses red blood cells 0.1 pH unit higher
      than wild-type viruses. This higher fusion pH may allow more efficient release of
      nucleocapsids from endosomes and contribute to the enhanced RNA synthesis. The
      efficient RNA synthesis assists virus survival at low inocula or under stringent
      growth conditions, such as the presence of antiviral agents. NWS-Mvi induces
      apoptosis in infected cells more readily than wild-type viruses, apparently as a
      consequence of enhanced production of viral mRNA. Since growth of NWS-Mvi is more
      efficient, apoptosis may play a positive role in viral replication by removing
      cells that have already been infected from those capable of making more virus.

PMID- 11451483
TI  - Rescue of viral haemorrhagic septicaemia virus minigenomes by helper virus.
AB  - A mammalian expression vector containing the bacterial chloramphenicol
      acetyltransferase (CAT) gene was used to demonstrate that CAT could be
      successfully used as a reporter system in fish cells growing at low temperatures.
      We then constructed a viral haemorrhagic septicaemia virus (VHSV) minigenome by
      cloning the CAT reporter gene between the viral leader and trailer sequences.
      This construct was used in transfection experiments with helper VHSV to
      demonstrate that the minigenome can be encapsidated and transcribed by helper
      virus proteins. In addition, passaging of viruses collected from cells expressing
      the minigenome showed that the minigenome was being packaged and replicated in
      the presence of helper virus. These experiments provide the initiating steps for
      a reverse genetics system for VHSV.

PMID- 11451484
TI  - Jatobal virus is a reassortant containing the small RNA of Oropouche virus.
AB  - Jatobal (JAT) virus was isolated in 1985 from a carnivore (Nasua nasua) in
      Tucurui, Para state, Brazil and was classified as a distinct member of the Simbu
      serogroup of the Bunyavirus genus, family Bunyaviridae on the basis of
      neutralization tests. On the basis of nucleotide sequencing, we have found that
      the small (S) RNA of JAT virus is very similar (>95% identity) to that of
      Oropouche (ORO) virus, in particular, the Peruvian genotype of ORO virus. In
      comparison, limited nucleotide sequencing of the G2 protein gene, encoded by the
      middle (M) RNA, of JAT and ORO viruses, revealed relatively little identity
      (<66%) between these two viruses. Neutralization tests confirmed the lack of
      cross-reactivity between the viruses. These results suggest that JAT virus is a
      reassortant containing the S RNA of ORO virus. JAT virus was attenuated in
      hamsters compared to ORO virus suggesting that the S RNA of ORO virus is not
      directly involved in hamster virulence.

PMID- 11451485
TI  - Inhibition of nuclear export of ribonucleoprotein complexes of influenza virus by
      leptomycin B.
AB  - We have studied nuclear export of influenza virus components using an in vitro
      transport system with digitonin-treated infected cells. We first monitored the
      efficiency of export of the viral ribonucleoprotein (vRNP) complex by analyzing
      viral components with western blotting. We used leptomycin B (LMB), an inhibitor
      of nuclear export signal (NES)-and its receptor, CRM1/Exportin1-mediated protein
      export. LMB efficiently inhibited vRNP export, while it did not affect the
      subcellular localization and export of matrix protein (M) 1 and nonstructural
      protein (NS) 2. Second, indirect immunofluorescence assays also revealed that
      vRNP export is sensitive to LMB. NS2 in NS2-transfected cells was not accumulated
      in nuclei in the presence of LMB, while NS2 in infected cells was found slightly
      accumulated in nuclei in the presence of LMB. Finally, we performed in vitro RNA
      synthesis assays using digitonin-treated infected cells and exported fractions.
      The exported vRNP was RNA synthesis-competent. Analyses using glycerol density
      gradients showed that a major fraction of M1 and NS2 was not complexed with the
      exported vRNP. These results suggest that nuclear export of RNA synthesis
      competent vRNP is dependent on a LMB-sensitive pathway and that there would be
      two types of NS2, i.e. LMB-sensitive and -insensitive NS2. The involvement of
      viral late proteins in vRNP export during late stages of infection is discussed.

PMID- 11451486
TI  - Extracellular truncated influenza virus nucleoprotein.
AB  - In the culture medium of MDCK cells infected with influenza
      A/Duck/Ukraine/1/63(H3N8) virus two kinds of virus nucleoprotein (NP) are
      detected: full-length 56 kDa NP and truncated 53 kDa NP. However, in infected
      cells 53 kDa NP may be detected only at short pulse and after 10 min chase it
      becomes nondetectable. The extracellular truncated 53 kDa NP is detected in free
      RNP, and not in the virions. Both extracellular free 53 and 56 kDa NP in the
      virions are completely oligomerized. Several data argue against the possibility
      of extracellular 53 kDa NP formation being a result of extracellular 56 kDa NP
      proteolytic degradation. Thus, the accumulation of extracellular 53 kDa NP takes
      place only in the course of infection, and the amount of 53 kDa NP is not
      increased during prolonged storage of cell-free culture medium at +37 degrees C.
      Moreover, all extracellular 56 kDa NP of A/Duck/Ukraine/1/63 influenza virus is
      present in the oligomeric form, and the latter, in contrast to the mononeric
      form, is highly resistant to proteases. The possibility is discussed that in the
      course of A/Duck/Ukraine/1/63 (H3N8) influenza virus infection a fraction of the
      synthesized 56 kDa monomeric NP undergoes the proteolytic cleavage in the
      infected cells before oligomerization and forms the 53 kDa NP. This 53 kDa NP is
      then oligomerized, enters the RNP and is quickly secreted from the cells.

PMID- 11451487
TI  - Virulent Newcastle disease in Australia: molecular epidemiological analysis of
      viruses isolated prior to and during the outbreaks of 1998-2000.
AB  - Gene sequence analysis of fusion (F) gene cleavage motifs and haemagglutinin
      neuraminidase (HN) carboxyl-terminal extension sequences was used to analyse
      Newcastle disease viruses (NDV) associated with virulent outbreaks of the disease
      which occurred in New South Wales, Australia in 1998-2000. PCR fragments were
      amplified directly from diseased tissue or allantoic fluids and sequence analyses
      used for phylogenetic comparisons between these viruses and Australian reference
      NDV. F and HN gene sequence comparison showed a strong relationship to sequences
      derived from endemic Australian NDV rather than those of overseas viruses or wild
      bird isolates. Prior to notification of the 1998 outbreak, an NDV was isolated
      from chickens suffering respiratory disease that appeared to be the progenitor
      virus from which the virulent virus originated. In turn, these viruses are
      closely related to two previously isolated 'ancestor' viruses that have the same
      unique HN extension sequence.

PMID- 11451488
TI  - Transport of viral proteins to the apical membranes and interaction of matrix
      protein with glycoproteins in the assembly of influenza viruses.
AB  - Influenza virus assembly and morphogenesis require transport of viral components
      to the assembly site at the apical plasma membrane of polarized epithelial cells
      and interaction among the viral components. In this report we have discussed the
      apical determinants present in the transmembrane domain (TMD) of influenza virus
      hemagglutinin (HA) and neuraminidase (NA), and the interaction of M1 with
      influenza virus HA and NA. Earlier studies have shown that the NA and HA TMDs
      possess determinant(s) for apical sorting and raft-association (Kundu et al.,
      1996. J. Virol 70, 6508-6515; Lin et al., 1998. J. Cell Biol. 142, 51-57).
      Analysis of chimeric constructs between NA and TR (human transferring receptor)
      TMDs and the mutations in the NA and HA TMD sequences showed that the COOH
      terminus of the NA TMD and NH(2) terminus of the HA TMD encompassing the
      exoplasmic leaflet of the lipid bilayers were significantly involved in lipid
      raft-association and that apical determinants were not discrete sequences but
      rather dispersed within the TMD of HA and NA. These analyses also showed that
      although both signals for apical sorting and raft-association resided in the NA
      TMD, they were not identical and varied independently. Interactions of M1 protein
      with HA or NA, the influenza virus envelope glycoproteins, were investigated by
      TX-100 detergent treatment of membrane fractions and floatation in sucrose
      gradients. Results from these analyses showed that the interaction of M1 with
      mature HA and NA, which associated with the detergent-resistant lipid rafts
      caused an increased detergent-resistance of the membrane-bound M1 and that M1
      interacted with HA and NA both in influenza virus-infected cells as well as in
      recombinant vaccinia virus-infected cells coexpressing M1 with HA and/or NA.
      Furthermore, both the cytoplasmic tail and the TMD of HA caused an increased
      detergent-resistance of the membrane-bound M1 supporting their interaction with
      M1. Immunofluorescence analysis by confocal microscopy also showed colocalization
      supporting the interaction of M1 with HA and NA at the cell surface and during
      exocytic transport both in influenza virus-infected cells as well as in
      coexpressing cells.

PMID- 11451489
TI  - Incidence of hantavirus infections in Belgium.
AB  - Over the last two decades, and from the moment that serological detection was
      possible, human hantavirus infections have been documented in most European
      countries. This paper summarises the available data on hantavirus cases in
      Belgium. These data enable the demonstration of the existence of a 3-year
      epidemic cycle in Belgium, which is apparently linked to rodent population
      dynamics.

PMID- 11451490
TI  - Genetic characterization of contemporary wild-type measles viruses from Vietnam
      and the People's Republic of China: identification of two genotypes within clade
      H.
AB  - Genetic characterization was conducted on 17 wild-type measles viruses isolated
      near Hanoi, Vietnam, during 1998 as well as on eight viruses isolated in the
      Hunan, Hainan, Shandong, and Anhui provinces of the People's Republic of China
      during 1995, 1998, and 1999. Previous studies had shown that, compared to wild
      type measles viruses found in other parts of the world, wild-type viruses from
      China were genetically distinct and comprised a new clade of viruses, clade H. In
      this study, sequence analyses of the nucleotides coding for the COOH terminal 150
      amino acids of the nucleoprotein (N) and the entire hemagglutinin (H) protein
      indicated that although all of the viruses from Vietnam were members of clade H,
      they were clearly distinct from the Chinese viruses. With the exception of
      MVi/Beijing.China/94/1, the Vietnamese viruses differed from all of the Chinese
      viruses by at least 3.5 and 2.5% at the nucleotide level for the N and H genes,
      respectively. These data suggest that clade H should be divided into two
      genotypes with the Chinese viruses placed in genotype H1 and the Vietnamese
      viruses in genotype H2. Sequence analysis of measles viruses imported into the
      United States from either China or Vietnam demonstrated that this designation of
      genotypes will be helpful in future measles surveillance activities.

PMID- 11451491
TI  - Molecular evolution of influenza A/H3N2 viruses in the province of Quebec
      (Canada) during the 1997-2000 period.
AB  - In this study, we compared antigenic (hemagglutination inhibition (HI) assay) and
      molecular (sequencing of the hemagglutinin (HA1) gene) characterization of
      influenza isolates collected in the Province of Quebec (Canada) during the last
      three flu seasons (1997-2000). Twenty-three isolates were tested by a standard HI
      assay and 37 by sequencing of the HA1 gene for their homology to the A/H3N2
      vaccine strains A/Wuhan/359/95 (1997-1998) and A/Sydney/5/97 (1998-1999 and 1999
      2000). By HI, two isolates were antigenically similar to A/Wuhan/359/95 (both
      from 1997 to 1998), 16 were similar to A/Sydney/5/97 (1997-2000) and no
      conclusions could be inferred for the other five isolates due to identical HI
      titers for the two vaccine strains (n=4) or insufficient viral titer (n=1).
      Sequence analysis revealed that four isolates from 1997 to 1998 were related to
      A/Wuhan/359/95 whereas the others (n=4) from 1997 to 1998, as well as all
      isolates from 1998 to 1999 (n=18) and 1999 to 2000 (n=11) were closer to
      A/Sydney/5/97. The mean number of amino acid differences for the 33 A/Sydney/5/97
      like isolates compared with the homologous vaccine strain was 6.3 (1.9%), 9.2
      (2.8%) and 13.6 (4.1%) for those collected in 1997-1998, 1998-1999, and 1999
      2000, respectively. Phylogenetic analysis confirmed that a progressive drift
      occurred among our A/H3N2 influenza isolates over the last three flu seasons.
      Furthermore, it revealed that isolates collected during the last two flu seasons
      were in fact more related to A/Panama/2007/99 (2000-2001 vaccine strain) than to
      A/Sydney/5/97. Our studies suggest that molecular analysis of the HA1 gene should
      complement the HI assay for a more accurate analysis of influenza A virus drift.

PMID- 11451492
TI  - An in vivo/in vitro comparison with a leuprolide osmotic implant for the
      treatment of prostate cancer.
AB  - An osmotically driven implantable system was designed and characterized for the
      delivery of leuprolide over a year-long duration. Leuprolide has been used in the
      treatment of prostate cancer since the 1980s. The DUROS implant consists of a
      titanium alloy cylinder, measures 4 mm in diameter by 45 mm in length and holds
      approximately 150 microl of formulation. Stability studies indicated that
      leuprolide was stable, as a solution formulation in DMSO, for several years at 37
      degrees C. In vitro release rate testing, at weekly intervals, showed zero-order
      delivery for 1 year. DUROS implants demonstrated release rates that were
      reproducible and similar to one another after storage at 25 degrees C for 18
      months prior to testing. In vivo studies, with implants placed subcutaneously,
      revealed delivery rates comparable to those observed under in vitro conditions.
      Leuprolide stability was also comparable between in vivo and in vitro conditions.
      Steady leuprolide serum levels produced by the implant resulted in the desired
      pharmacodynamic efficacy endpoint of testosterone suppression, both in canines
      and in humans. The good agreement between in vivo/in vitro delivery rates was as
      expected for a delivery system based on the principles of osmosis.

PMID- 11451493
TI  - Auto-catalyzed poly(ortho ester) microspheres: a study of their erosion and drug
      release mechanism.
AB  - A study has been carried out to investigate the degradation and protein release
      mechanisms of BSA-loaded microspheres made with auto-catalyzed poly(ortho esters)
      (POEs) of varying diol composition and molecular weights. Due to the instability
      of the POE/dichloromethane primary emulsion, microspheres made using the W/O/W
      double emulsion solvent extraction/evaporation method showed a multivesicular
      internal structure. An O/W single emulsion process yielded dense POE
      microspheres. Using electron scanning microscopy, the microspheres were observed
      to erode throughout their matrices with increasing internal pore sizes and a
      steady loss of mass. However, despite a substantial weight loss of almost 80%
      after an in vitro period of 129 days, the molecular weight of the polymer
      remained relatively unchanged with loss averaging about 18 and 32% for low- and
      high-molecular-weight POEs, respectively. Such constancy in molecular weight was
      similarly reflected in the glass transition temperature of the degrading
      microspheres. The differences in both the molecular weight loss and
      polydispersity index changes depended largely on the molecular weight of the
      polymer. For protein release of POE microspheres, an induction period followed by
      BSA release for a period of 3 to 10 days was observed. The lag time depended on
      the hydrophilicity and the molecular weight of the polymer as well as the
      morphology of the microspheres. Protein release was incomplete, possibly due to
      the slow degradation of the POE polymers, protein aggregation and protein
      degradation.

PMID- 11451494
TI  - Investigation on a novel core-coated microspheres protein delivery system.
AB  - Among the different approaches to achieve protein delivery, the use of polymers,
      specifically biodegraded, holds great promise. In this work, a new microsphere
      delivery system composed of alginate microcores surrounded by a biodegradable
      poly-DL-lactide-poly(ethylene glycol (PELA) was designed to improve the loading
      efficiency and stability of proteins. Alginate was solidified by calcium (MS-1),
      polylysine (MS-2) and chitosan (MS-3), respectively, to form different
      microcores. Human Serum Albumin (HSA), used as a model protein, was efficiently
      entrapped within the alginate microcores using a high-speed stirrer and then
      microencapsulated into PELA copolymer using a w/o/w solvent extraction method.
      DSC analysis of the microspheres revealed the efficient encapsulation of the
      alginate microcores, while the microcores were dispersed in the PELA matrix. SDS
      PAGE results showed that HSA kept its structural integrity during encapsulation
      and release procedure. Microspheres were characterized in terms of morphology,
      size, loading efficiency, in vitro degradation and protein release. The
      degradation profiles were characterized by measuring the loss of microsphere
      mass, the decrease of polymer intrinsic viscosity and the reduction of PEG
      content of PELA coat. The release profiles were investigated from the measurement
      of protein presented in the release medium at various intervals. The results were
      that the degradation rate of these core-coated microspheres was MS-2>MS-1>MS-3.
      The extent of burst release from the core-coated microspheres in the initial
      protein release was lower than the 27% burst release from the conventional
      microspheres. In conclusion, the work presents a new approach for macromolecular
      drugs (such as protein, peptide drugs) delivery. The core-coated microspheres
      system may have potential use as a carrier for drugs that are poorly absorbed
      after oral administration.

PMID- 11451495
TI  - Controlled release of clot-dissolving tissue-type plasminogen activator from a
      poly(L-glutamic acid) semi-interpenetrating polymer network hydrogel.
AB  - With the aim of developing an effective therapeutic modality for treatment of
      thrombosis, a tissue-type plasminogen activator (t-PA)-loaded porous poly(L
      glutamic acid) (PLGA) semi-interpenetrating polymer network (semi-IPN) hydrogel
      was developed as a possible local drug delivery system. Porous structure of
      hydrogel was essential in this system to yield a large surface area so that t-PA
      release could be facilitated. This semi-IPN hydrogel was prepared using the
      method of free-radical polymerization and crosslinking of polyethylene glycol
      (PEG)-methacrylate through the PLGA network. Sodium bicarbonate (NaHCO(3)) was
      added to function as a foaming agent under acidic conditions, rendering the semi
      IPN hydrogel to be porous. While the added NaHCO(3) provided gas foam in the
      reaction mixture, the pH in the hydrogel increased to about 7 to 8, which
      stimulated the polymerization. The porous structure that was presented at both
      the surface and sublayer was stabilized during hydrogel formation and freeze
      drying. The hydrogel thus prepared possessed a porous structure of 10-20 microm
      in diameter, as determined by scanning electron microscopy. Results showed that
      the above hydrogel preparation process did not significantly alter the specific
      activity of the entrapped t-PA with regard to plasminogen activation and fibrin
      clot lysis ability. The t-PA release from this semi-IPN hydrogel was examined by
      measuring the plasmin activity using the chromogenic substrate S-2251. Findings
      in this paper demonstrated that the porous structure of the hydrogel facilitated
      t-PA release when compared to the dense structure. Aside from the porous
      structure, other factors including the content of the crosslinker, PLGA and t-PA
      could all be varied to regulate t-PA release from the hydrogel. These results
      suggest that a porous PLGA semi-IPN hydrogel could potentially be a useful local
      delivery system to release active t-PA primarily at the site of a thrombus.

PMID- 11451496
TI  - pH compartmented w/o/w multiple emulsion: a diffusion study.
AB  - In order to develop w/o/w emulsions characterized by two separate aqueous phases
      of different pH, a preliminary study was carried out to obtain a better insight
      into the possible diffusion processes taking place between an inner acidic
      aqueous phase and an external phase of higher pH (pH approximately 6). In fact,
      such systems could be of great interest for pharmaceutical use. For this purpose,
      a model emulsion was formulated. The study of pH and conductivity showed that
      acidic species transport take place between the two aqueous compartments. The
      three main release mechanisms that might be responsible for this passage across
      the oil phase were investigated: breakdown of oil globules, facilitated transport
      by surfactant micelles across the oil phase or by Fickian diffusion. It appears
      that this last mechanism was involved. In order to control this diffusion
      process, an alkaline species, octadecylamine was introduced in the oil phase.
      This compound could form an ion pair with the lactate ion at the interface of the
      external aqueous phase and the oil phase, thus, limiting the acidification of the
      external aqueous phase.

PMID- 11451497
TI  - On-off transport through a thermoresponsive hydrogel composite membrane.
AB  - A novel thermoresponsive composite membrane is described through which the
      permeation of molecules is dependent on the temperature of the milieu. The
      thermoresponsive composite membranes utilise a thermosensitive crosslinked
      polymeric hydrogel, which possesses a volume phase transition temperature (VPTT).
      The hydrogel was polymerised in situ within the pores of a sintered glass filter,
      through which significant permeation of molecules only occurred at temperatures
      above the VPTT of the hydrogel. It was found that the permeation of molecules
      through the thermoresponsive composite membranes could be modulated by changing
      the environmental temperature.

PMID- 11451498
TI  - Mechanism of the ultrasonic activation of micellar drug delivery.
AB  - The mechanism of the ultrasonic enhancement of the uptake of cytotoxic drugs,
      doxorubicin (DOX) and ruboxyl (Rb) by HL-60 cells from Pluronic micelles was
      studied. DOX and Rb sorption from either PBS or micellar Pluronic solutions is
      described by Langmuir-type isotherms characteristic of substrates with limited
      number of sorption centers. The sorption limits for Rb from PBS and Pluronic were
      considerably higher than those for DOX, presumably due to much higher Rb
      partitioning into cell membranes. The overall number of drug sorption centers for
      both drugs decreased in the presence of Pluronic implying the effect of Pluronic
      on the DNA conformation, which was confirmed by the electron paramagnetic
      resonance (EPR) experiments using Rb as a spin probe. Ultrasound increased drug
      uptake by the cells from PBS and Pluronic solutions. The fluorescence microscopy
      and flow cytometry experiments using fluorescently-labeled Pluronic showed that
      ultrasound enhanced both the intracellular uptake of Pluronic micelles and
      Pluronic trafficking into cell nuclei. A scheme is suggested that describes
      various equilibria controlling drug/cell interactions and effect of ultrasound on
      these equilibria. Under the action of ultrasound, the equilibrium between the
      micellar-encapsulated and free drug is shifted in the direction of free drug due
      to micelle perturbation; the equilibrium between extracellular and internalized
      drug is shifted to the intracellular drug due to the ultrasound-induced cellular
      changes that enhance the accessibility of various cellular structures to drug. An
      important advantage offered by ultrasound is that the same degree of the
      intracellular drug uptake may be achieved at a substantially lower drug
      concentration in the incubation medium.

PMID- 11451499
TI  - Evaluation of circulation profiles of liposomes coated with hydrophilic polymers
      having different molecular weights in rats.
AB  - The purpose of this study was to evaluate the circulating properties of liposomes
      coated with modified polyvinyl alcohol (PVA-R) having different molecular weights
      (6000, 9000 and 20000). The size controlled liposomes (egg phosphatidylcholine
      (or distearoylphosphatidylcholine):cholesterol=7:3 in a molar ratio) were
      prepared by the hydration method followed by sonication. Polymer coated liposomes
      were prepared by just mixing the resultant liposomal suspension and a polymer
      solution. The effects of polymer coating were evaluated by measuring the
      circulation time of the injected liposomes after i.v. administration in rats and
      the dispersing property of the liposomes in a biological condition. The
      circulation of the PVA-R coated liposomes was prolonged with increasing the
      molecular weight of PVA-R. The aggregation and/or fusion of the liposomes in the
      presence of serum in vitro was also depressed more by coating the liposomes with
      PVA-R having higher molecular weight. There was a good correlation between the
      circulation time and the physical stability of non-coated and the various PVA-R
      coated liposomes. The prolonged circulation time of PVA-R (molecular weight:
      20000) coated liposomes (ca. 1.3 mol% coating) was comparable to that of a
      stealth liposome prepared with 8 mol% of DSPE-PEG (molecular weight of PEG:
      2000).

PMID- 11451500
TI  - Direct compressible polymethacrylic acid-starch compositions for site-specific
      drug delivery.
AB  - The purpose of this study was to generate and characterize a direct compressible
      pH-sensitive excipient composition for controlled drug delivery. In acidic
      aqueous solutions, polymethacrylic acid (PMAA) forms complexes and precipitates
      with starch. As the extent of the interaction between PMAA and starch reaches a
      maximum at a weight ratio of 1:1.38 (PMAA/starch), this composition was used for
      the direct compression of tablets. These tablets (30 mg) showed no disintegration
      even after 2 days in a disintegration test apparatus according to the USP XXIII,
      in simulated gastric fluid at pH 1.2. In contrast, in 100 mM phosphate buffer pH
      7.0 they disintegrated within 40.25+/-8.42 min (mean+/-S.D., n=3). Control
      tablets of starch disintegrated within the first minute at both pH values.
      Dissolution studies with the model peptide peroxidase demonstrated no release
      within 120 min at pH 1.2, whereas at pH 7.0, 100% of the peptide was released
      within 330 min. Similar release profiles were obtained with the model drugs
      amoxicillin and rifampicin. In addition, the use of a PMAA-starch composition as
      a carrier matrix for peroxidase and amoxicillin provided a protective effect
      towards pepsin and hydrolytic degradation at pH 1.2, respectively. According to
      these results, the PMAA-starch composition may be a useful tool to overcome the
      very harsh environment of the stomach for future delivery systems.

PMID- 11451501
TI  - The in vitro evaluation of 'azo containing polysaccharide gels' for colon
      delivery.
AB  - This study reports on 'azo-polysaccharide gels', more specifically azo-inulin and
      azo-dextran gels, for colon drug delivery. Compared with azo-hydrogels which can
      be only degraded by reduction of the azo-groups, this study evaluates whether, in
      vitro, azo-polysaccharide gels can be degraded through both reduction of the azo
      groups in the crosslinks as well as enzymatic break down of the polysaccharide
      backbone. The azo-polysaccharide gels were synthesized by radical crosslinking of
      a mixture of methacrylated inulin or methacrylated dextran and N,N'
      bis(methacryloylamino)azobenzene (B(MA)AB) and were characterized by dynamic
      mechanical analysis and swelling measurements. Azo-dextran gels could be obtained
      from methacrylated dextran having low degree of substitution but not from lowly
      substituted methacrylated inulin. Increasing the amount of B(MA)AB resulted in
      denser azo-inulin and azo-dextran networks. Compared with their swelling in
      dimethylformamide, all azo-dextran gels became more swollen in water while azo
      inulin gels shrank upon exposure to water, indicating a more hydrophobic
      character of the azo-inulin gels. Break down of the inulin and dextran chains in
      the azo-polysaccharide gels by inulinase and dextranase, respectively, was
      observed. However, the degradation of azo-dextran gels by dextranase seemed to be
      more pronounced than the degradation of the azo-inulin gels by inulinase. In rat
      caecal content medium, reduction of the azo function in azo-inulin gels was not
      observed. This may be attributed to a low partitioning of nicotinamide-adenine
      dinucleotide phosphate (NADP(+)) in the gels.

PMID- 11451502
TI  - POE-PEG-POE triblock copolymeric microspheres containing protein. I. Preparation
      and characterization.
AB  - Poly(ortho ester) (POE)-poly (ethylene glycol) (PEG) triblock copolymers (POE-PEG
      POE) with different PEG contents were synthesised as carriers for controlled
      protein delivery. POE-PEG-POE microspheres containing bovine serum albumin (BSA)
      were prepared using a double-emulsion (water-in-oil-in-water) process. In this
      first paper of a two-part series, we report the fundamentals of the fabrication
      and characterization of POE-PEG-POE microspheres. Because the triblock copolymer
      is more hydrophilic than neat poly(ortho ester), the triblock copolymer yields a
      more stable first emulsion (water-in-oil) and a greater BSA encapsulation
      efficiency (90% vs. 30%). No BSA is found on POE-PEG-POE microsphere surfaces
      measured by X-ray photoelectron spectroscopy, while uniform BSA distributions are
      observed within the microspheres by confocal microscopy. SEM pictures show that
      an increase in PEG content results in microspheres with a denser cross-section
      because of a more stable first emulsion and better affinity between the copolymer
      and water. POE-PEG(20%)-POE suffers significant swelling during the fabrication
      process and yields the biggest microspheres. However, the POE-PEG(30%)-POE
      microspheres are much smaller since the dissolution loss of POE-PEG(30%)-POE in
      the external water phase may be much higher than that of POE-PEG(20%)-POE. The
      salt concentration in the external water phase significantly affects the
      morphology of the resultant microspheres. Microspheres with a dense wall are
      produced when using pure water as the external water phase. Polymer concentration
      has less impact on BSA encapsulation efficiency but has a considerable effect on
      microsphere size and morphology. Increasing the concentration of the polyvinyl
      alcohol emulsifier does not cause an obvious decrease in microsphere size.
      However, increased BSA loading results in bigger microspheres.

PMID- 11451503
TI  - POE-PEG-POE triblock copolymeric microspheres containing protein. II. Polymer
      erosion and protein release mechanism.
AB  - The first paper of this series presented the fabrication and characterization of
      POE-PEG-POE triblock copolymeric microspheres containing protein. In this paper,
      we focus on the polymer erosion and the mechanism of protein release. Fourteen
      week in vitro behaviors of POE-PEG-POE microspheres loaded with bovine serum
      albumin (BSA) have been monitored. SEM micrographs reveal that after 14-week
      incubation in PBS buffer, pH 7.4, 37 degrees C, the polymeric particles remain
      spherical despite mass loss of almost 90%. On the other hand, molecular weight
      undergoes a high initial loss of 38% and 44% during the first 2-week incubation
      for POE-PEG(5%)-POE and POE-PEG(10%)-POE, respectively. Then, it keeps relatively
      unchanged over 12 weeks. However, POE-PEG(20%)-POE copolymer provides a better
      compatibility between the POE and PEG blocks. Hydrolysis is homogeneous through
      the polymer backbone. Thus, its molecular weight remains relatively constant and
      mass loss shows quite sustained over the 14-week in vitro release. The similar
      phenomena are observed in the polydispersity index of the degrading copolymers.
      SDS-PAGE of the encapsulated BSA within the POE-PEG(5%)-POE microspheres displays
      that the structural integrity of BSA is intact for at least 8 weeks due to a mild
      environment provided by the copolymer. In addition, XPS and FTIR are utilized to
      investigate protein behaviors in the degrading microspheres. Protein release from
      the POE-PEG-POE microspheres shows a biphasic pattern, characterized by an
      initial stage followed by a non-detectable release. The non-release phase is
      dominated by either slow polymer degradation or dense microsphere matrix
      structures. The microsphere formulation is optimized and a sustained protein
      release over 2 weeks is achieved by using POE-PEG(20%)-POE at a high protein
      loading.

PMID- 11451504
TI  - Drug physical state and drug-polymer interaction on drug release from chitosan
      matrix films.
AB  - Four different grades of chitosan varying in molecular weight and degree of
      deacetylation were used to prepare chitosan films. Salicylic acid and
      theophylline were incorporated into cast chitosan films as model acidic and basic
      drugs, respectively. Crystalline characteristics, thermal behavior, drug-polymer
      interaction and drug release behaviors of the films were studied. The results of
      Fourier transform infrared and solid-state 13C NMR spectroscopy demonstrated the
      drug-polymer interaction between salicylic acid and chitosan, resulting in
      salicylate formation, whereas no drug-polymer interaction was observed in
      theophylline-loaded chitosan films. Most chitosan films loaded with either
      salicylic acid or theophylline exhibited a fast release pattern, whereas the high
      viscosity chitosan films incorporated with salicylic acid showed sustained
      release patterns in distilled water. The sustained release action of salicylic
      acid from the high viscosity chitosan films was due to the drug-polymer
      interaction. The mechanism of release was Fickian diffusion control with
      subsequent zero order release. It was suggested that the swelling property,
      dissolution characteristics of the polymer films, pK(a) of drugs and especially
      drug-polymer interaction were important factors governing drug release patterns
      from chitosan films.

PMID- 11451505
TI  - Transdermal drug delivery enhanced and controlled by erbium:YAG laser: a
      comparative study of lipophilic and hydrophilic drugs.
AB  - The influence of an erbium:YAG laser on the transdermal delivery of drugs across
      skin was studied in vitro. Indomethacin and nalbuphine, which have the same
      molecular weight, were selected as model lipophilic and hydrophilic drugs,
      respectively, to compare skin permeation by laser treatment. The results indicate
      a significant increase in the permeation of indomethacin and nalbuphine across
      skin pretreated with an erbium:YAG laser. The laser had a greater effect on the
      permeation of hydrophilic molecules which usually possess low permeability. The
      laser intensity and its spot size were found to play an important role in
      controlling transdermal delivery of drugs. Permeation of the hydrophilic drug
      increased following an increase of laser energy. On the other hand, a different
      result was observed for the lipophilic drug transported across laser-treated
      skin. The stratum corneum (SC) layer in skin could be partly ablated by the
      erbium:YAG laser. The barrier function of the SC may also be modulated by a lower
      intensity of the laser without affecting the viability and structure of the
      epidermis/dermis as determined by histological observations. However,
      ultrastructural alteration of the epidermis/dermis may be caused by laser
      treatment. Use of an erbium:YAG laser is a good method for enhancing transdermal
      absorption of both lipophilic and hydrophilic drugs, because it allows precise
      control of SC removal, and this ablation of SC can be reversible to the original
      normal status.

PMID- 11451506
TI  - The preparation of the chronic hyper-endotoxemia experimental animal model by
      means of a drug delivery system.
AB  - A drug delivery system (DDS) consisting of lipopolysaccharide (LPS) as a drug and
      2-hydroxyethyl methacrylate (HEMA)-diethylene glycol dimethacrylate (2G) or 
      polyethylene glycol dimethacrylate (4G, 9G) copolymer was prepared, and used for
      the efficient preparation of an experimental animal model of chronic hyper
      endotoxemia. The release profiles of LPS in the in-vitro test were greatly
      influenced by the composition of HEMA-2G, 4G, 9G in the copolymer. It was found
      that LPS release from the DDS continued gradually and constantly throughout 2
      weeks. In the in-vivo experiment with rats, the DDS maintained a high blood
      concentration level of LPS for 3 days. These results strongly suggest the
      possibility of convenient and reproducible preparation of a chronic hyper
      endotoxemia animal model.

PMID- 11451507
TI  - Controlled release of biomolecules from temperature-sensitive hydrogels prepared
      by radiation polymerization.
AB  - Poly(acryloyl-L-proline methyl ester)-based hydrogels containing 1 and 5% of a
      crosslinking agent were studied as drug delivery systems. The drug loading
      properties were investigated by matrix incubation into solutions containing
      biomolecules with molecular weight ranging between 300 and 65,000 Da. The loading
      yield was found to depend on both the crosslinking degree and the molecular
      weight of the drug. In vitro release studies were carried out with both swollen
      and dry matrices loaded with gentamicin, isoniazid and insulin. Gentamicin and
      isoniazid were released by a bimodal Fickian diffusion with a remarkable burst
      that was found to depend on both matrix crosslinking degree and physical state.
      In vivo, the subcutaneous implantation into mice of the isoniazid loaded matrices
      allowed for an efficient drug release for 800 h. In vitro insulin was released
      from the swollen matrices for 1500 h by diffusional Fickian mechanism while the
      dry ones displayed a lag time followed by Fickian diffusion release. The
      subcutaneous implantation of the insulin-loaded matrices into diabetic mice
      induced a remarkable decrease in the glucose concentrations in blood. In
      particular, the dry 1% matrices were found to maintain a low glucose level for
      700 h.

PMID- 11451508
TI  - Thermo-responsive release from interpenetrating porous silica-poly(N
      isopropylacrylamide) hybrid gels.
AB  - Novel thermo-responsive inorganic-organic hybrid gels were prepared by
      hybridizing porous silica and poly(N-isopropylacrylamide) gels (PNIPAAm gel). The
      internal pores of the silica were filled with PNIPAAm gel to give a thermo
      responsive drug reservoir. Brilliant blue FCF (BB) was also added to the hybrid
      gels for release. The BB release rate was faster above the lower critical
      solution temperature (LCST) of the PNIPAAm gel than below the LCST. When the
      temperature changed across the LCST, reversible and thermo-responsive release
      behavior was observed. The transition of the release behavior upon changing the
      temperature was similar to the behavior of the PNIPAAm gel itself. The BB release
      rate can be controlled simply by changing the amount of PNIPAAm gel loaded into
      the silica.

PMID- 11451509
TI  - Topical application of acyclovir-loaded microparticles: quantification of the
      drug in porcine skin layers.
AB  - The goal of this work was to increase the amount of acyclovir (ACV) in the basal
      epidermis, site of Herpes virus simplex infections, using microparticles as
      carriers. Poly(D,L-lactic-co-glycolic acid) microparticles loaded with ACV were
      prepared using a solvent evaporation technique. ACV distribution into porcine
      skin after topical application of microparticles for 6, 24 and 88 h, was
      determined by horizontal slicing of the skin. An ACV suspension served for
      comparison. The results showed that, at 6 and 24 h, the quantity of the drug in
      the basal epidermis with the microparticles, is similar to that obtained with the
      ACV suspension. However, after 88 h, the ACV reservoir in the basal epidermis was
      higher with the microparticles compared with the control suspension. This could
      be explained by the controlled drug release produced by the vector in the basal
      epidermis. Besides, at 88 h the amount of ACV detected in the receptor chamber of
      the diffusion cells was much lower with the microparticles than with the
      suspension. This type of carrier can improve acyclovir topical therapy since it
      increases drug retention in the basal epidermis and consequently increases the
      time intervals between doses.

PMID- 11451510
TI  - Intracytoplasmic gene delivery for in vitro transfection with cytoskeleton
      specific immunoliposomes.
AB  - A novel and highly efficient method of in vitro gene transfection has been
      developed. This method employs direct intracytoplasmic gene delivery into
      embryonic cardiocytes using neutral cytoskeletal-antigen specific immunoliposomes
      (CSIL). These immunoliposomes target cardiocytes specifically under reversible
      hypoxic conditions. Two independent reporter genes, pGL2 and pSV-beta
      galactosidase, were used to verify CSIL-transfection (CSIL-fection). The
      efficiency of CSIL-fection with firefly luciferase pGL2 vector was 30+ times
      greater than controls consisting of hypoxic cardiocytes treated with plain
      liposomes (PL) or normoxic cardiocytes treated with CSIL, PL or naked DNA. CSIL
      fection was also compared to cationic liposome transfection. Net cationic
      liposome transfection appeared to be more efficient than CSIL-fection for pGL2
      vectors. However, a smaller number of viable cells was observed in the cationic
      liposome treated cultures than in the CSIL treated cultures. Therefore, to
      determine whether more cells were transfected with cationic liposomes or CSIL,
      pSV-beta-galactosidase vector was used. CSIL-fection with pSV-beta-galactosidase
      vector produced at least 40 times more transfected cells than those transfected
      with cationic liposomes. No transfection with pSV-beta-galactosidase vectors was
      obtained with IgG-liposome, PL or naked DNA treatments. Targeted enhanced
      efficiency of transfection by this novel method could have practical therapeutic
      applications in the genetic modification of cells ex vivo that could then be
      reimplanted into patients for gene therapy.

PMID- 11451512
TI  - Comparative single-strand conformation polymorphism (SSCP) and microscopy-based
      analysis of nitrogen cultivation interactive effects on the fungal community of a
      semiarid steppe soil.
AB  - The effects of nitrogen accretion on fungal diversity and community structure in
      early-seral (cultivated) and native (uncultivated) shortgrass steppe soils were
      evaluated using single-strand conformation polymorphism (SSCP) and microscopy in
      a comparative experiment. Selected haplotypes generated from fungal 18S gene
      fragments were also sequenced for species identification. Microscopy-based
      analyses showed significantly shorter fungal hyphal lengths in the early-seral
      control plots in comparison with the native control plots (P<0.0003), independent
      of nitrogen addition. Although diversity indices did not show significant
      differences between the plots, SSCP analyses indicated that fungal community
      structure differed in the native and early-seral control sites. In nitrogen
      amended sites, gene sequences from dominant haplotypes indicated a shift to a
      more common nitrogen-impacted fungal community. While nitrogen amendments appear
      to be more important than cultivation in influencing these soil fungal
      communities, hyphal lengths were only decreased due to cultivation. The use of
      microscopic and molecular techniques, as carried out in this study, provided
      integrative information concerning fungal community responses to wide spread
      stresses being imposed globally on terrestrial ecosystems, that is not provided
      by the individual techniques.

PMID- 11451511
TI  - Poly(lactic acid)-poly(ethylene glycol) nanoparticles as new carriers for the
      delivery of plasmid DNA.
AB  - The purpose of the present work was to produce and characterize poly(lactic acid)
      poly(ethylene glycol) (PLA-PEG) nanoparticles (size lower than 300 nm) containing
      a high loading of plasmid DNA in a free form or co-encapsulated with either
      poly(vinyl alcohol) (PVA) or poly(vinylpyrrolidone) (PVP). The plasmid alone or
      with PVA or PVP was encapsulated by two different techniques: an optimized w/o/w
      emulsion-solvent evaporation technique as well as by a new w/o emulsion-solvent
      diffusion technique. Particle size, zeta potential, plasmid DNA loading and in
      vitro release were determined for the three plasmid-loaded formulations. The
      influence of the initial plasmid loadings (5, 10, 20 microg plasmid DNA/mg PLA
      PEG) on those parameters was also investigated. The plasmid loaded into the
      nanoparticles and released in vitro was quantified by fluorimetry and the
      different molecular forms were identified by gel electrophoresis. PLA-PEG
      nanoparticles containing plasmid DNA in a free form or co-encapsulated with PVA
      or PVP were obtained in the range size of 150-300 nm and with a negative zeta
      potential, both parameters being affected by the preparation technique.
      Encapsulation efficiencies were high irrespective of the presence of PVA or PVP
      (60-90%) and were slightly affected by the preparation technique and by the
      initial loading. The final plasmid DNA loading in the nanoparticles was up to 10
      12 microg plasmid DNA/mg polymer. Plasmid DNA release kinetics varied depending
      on the plasmid incorporation technique: nanoparticles prepared by the w/o
      diffusion technique released their content rapidly whereas those obtained by the
      w/o/w showed an initial burst followed by a slow release for at least 28 days. No
      significant influence of the plasmid DNA loading and of the co-encapsulation of
      PVP or PVA on the in vitro release rate was observed. In all cases the conversion
      of the supercoiled form to the open circular and linear forms was detected. In
      conclusion, plasmid DNA can be very efficiently encapsulated, either in a free
      form or in combination with PVP and PVA, into PLA-PEG nanoparticles.
      Additionally, depending on the processing conditions, these nanoparticles release
      plasmid DNA either very rapidly or in a controlled manner.

PMID- 11451513
TI  - Reversible transition between active and dormant microbial states in soil.
AB  - The rate of respiration obtained in the substrate-induced respiration (SIR)
      method can be divided into the respiration rate of growing (r) and non-growing
      (K) microorganisms. The fraction of r is generally small (5-20%) in soils with no
      recent addition of substrates, but can be 100% in soils with high substrate
      availability. This suggests that substrate availability determines the proportion
      of biomass between these groups, and implies that transitions between them can
      take place reversibly. These hypotheses were tested by adding three different
      amounts of glucose which induced first-order, zero-order, and growth-associated
      respiration kinetics to three soils at four pre-incubation times (4, 12, 27, and
      46 days) before the SIR measurement. An abiotic flush of CO(2) in the SIR
      measurement was detected and corrected for before data analysis. Accumulated
      CO(2)-C over 4 days after glucose addition, corrected for the respiration in
      unamended controls, corresponded to 41-50% mineralization of the glucose-C, and
      the relative amount mineralized by each soil was independent of the glucose
      amount added. The high glucose concentration gave an increased SIR, which
      reverted to the initial value within 27-46 days. In a specific sample, the
      maximum respiration rate induced during the pre-incubation, and the amount of
      organisms transformed from the K to the r state, as quantified in respiration
      rate units in the SIR measurement, were identical to each other, and these
      parameters were also highly correlated to the initial glucose concentration. The
      K-->r transition was very fast, probably concurrent with the instantaneous
      increase in the respiration rate obtained by the glucose amendment. Thereafter, a
      slow first-order back-transition from the r to the K state ensued, with half
      lives of 12, 23, and 70 days for the three soils. The results suggest the
      existence of community-level controls by which growth within or of the whole
      biomass is inhibited until it has been completely transformed into the r state.
      The data also suggest that the microbial specific activity is not related to the
      availability of exogenous substrate in a continuous fashion, rather it responds
      as a sharp transition between dormant and fully active. Furthermore, the inherent
      physiological state of the microbial biomass is strongly related to its history.
      It is proposed that the normal dynamics of the soil microbial biomass is an
      oscillation between active and dormant physiological states, while significant
      growth occurs only at substantial substrate amendment.

PMID- 11451514
TI  - Growth of a bacterial consortium on triclosan.
AB  - Triclosan is a polychlorinated hydroxy diphenylether that has been widely used as
      an antimicrobial compound. An enrichment using triclosan as a sole source of
      carbon and energy yielded a consortium of bacteria capable of growing on this
      compound. The dichloro ring was partially mineralized, resulting in the
      conversion of approximately 35% of the [(14)C]triclosan to [(14)C]CO(2). Use of
      molecular fingerprinting techniques and 16S rDNA cloning and sequencing aided in
      the identification and eventual isolation of an auxotrophic Sphingomonas-like
      organism, strain Rd1, which was able to partially mineralize triclosan when grown
      on complex media.

PMID- 11451515
TI  - Molecular microbial analysis of Bifidobacterium isolates from different
      environments by the species-specific amplified ribosomal DNA restriction analysis
      (ARDRA).
AB  - One hundred and six isolates of the genus Bifidobacterium, isolated from
      different environments (mainly gastrointestinal), were identified and classified
      taxonomically to species level by amplified ribosomal DNA restriction analysis.
      Two restriction endonucleases (Sau3AI and BamHI) were chosen for aligning the 16S
      rRNA sequences of 16 bifidobacterial species retrieved from various databases, to
      obtain species-specific restriction patterns. A rapid and accurate identification
      scheme was obtained by comparing the resulting 16S rDNA digestion profiles of 16
      Bifidobacterium type-strains and 90 strains of various origins. All of the
      investigated strains were previously confirmed at the species level as belonging
      to the genus Bifidobacterium by fluorescence in-situ hybridisation and by
      polymerase chain reaction amplification with genus- and species-specific primers.
      The present work demonstrates that species-specific detection of Bifidobacterium
      adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium
      breve, Bifidobacterium catenulatum, Bifidobacterium coryneforme, Bifidobacterium
      cuniculi, Bifidobacterium dentium, Bifidobacterium infantis, Bifidobacterium
      lactis, Bifidobacterium longum, Bifidobacterium suis, Bifidobacterium magnum,
      Bifidobacterium pseudolongum, Bifidobacterium pseudocatenulatum and
      Bifidobacterium pullorum present in different micro-ecological environments (e.g.
      gastrointestinal tract) can be accomplished in a reliable, rapid and accurate
      manner, circumventing the recognised deficiencies of traditional identification
      techniques.

PMID- 11451516
TI  - The contribution of halophilic Bacteria to the red coloration of saltern
      crystallizer ponds(1).
AB  - Analysis of the pigments extracted from solar saltern crystallizer ponds in Santa
      Pola near Alicante and on the Balearic island of Mallorca, Spain, showed that 5
      7.5% of the total prokaryotic pigment absorbance could be attributed to a novel
      carotenoid or carotenoid-like compound. This unidentified pigment was identical
      to the sole pigment present in Salinibacter ruber, the only described member of a
      newly discovered genus of red halophilic Bacteria related to the Cytophaga
      Flavobacterium-Bacteroides group. On the basis of fluorescence in situ
      hybridization experiments it has been shown that Salinibacter is an important
      component of the microbial community of Spanish saltern ponds. The red color of
      saltern crystallizer ponds may thus not only be due to red halophilic Archaea and
      to beta-carotene-rich Dunaliella cells as previously assumed, but may contain a
      bacterial contribution as well. The Salinibacter pigment was not detected in
      samples collected from crystallizer ponds of the salterns of Eilat, Israel, and
      only traces of it may have been present in the Newark, CA, USA, salterns. The
      community structure of the prokaryote community inhabiting saltern crystallizers
      thus shows significant geographic variations. Polar lipid analyses of the biomass
      collected from the Santa Pola salterns showed that the total contribution of
      Salinibacter and other Bacteria to the total biomass was minor, the most
      important component of the community being halophilic Archaea.

PMID- 11451517
TI  - Adaptation of Ruminococcus flavefaciens resulting in increased degradation of
      ryegrass cell walls.
AB  - This study investigated the long term adaptation of a ruminal bacterium to growth
      on four different plant cell wall substrates. No significant increase in
      degradation was detected for lucerne, barley straw or weeping lovegrass after 23
      serial subcultures of the cellulolytic rumen bacterium Ruminococcus flavefaciens
      strain 17 on each of these substrates. Significantly increased substrate
      degradation by R. flavefaciens strain 17 was however observed after 23
      subcultures on perennial ryegrass. The increase in dry matter solubilisation
      (from 24.3 to 39.5% in 24 h incubation and from 52.3 to 61% in 72 h) was at least
      partially due to an increase in solubilisation of xylose, glucose and arabinose.
      Enhanced growth of the adapted strains occurred on this substrate. Significant
      increases in xylanase and beta-xylosidase specific activities were detected but
      no effect was detected on xylanase profiles in zymogram analyses. Similar
      responses were observed for two cultures originally derived from single-colony re
      isolates. The most likely explanation for the observed adaptation involves
      selection for mutations affecting the regulation of xylanolytic enzymes.

PMID- 11451518
TI  - PCR-SSCP comparison of 16S rDNA sequence diversity in soil DNA obtained using
      different isolation and purification methods.
AB  - This study compared different methods of direct DNA extraction and purification
      from a silt loam soil and investigated the relationship between DNA quantity and
      sequence diversity. Five extraction methods and four purification techniques were
      investigated. Quantities of DNA extracted were between 3.4+/-0.55 and 54.3+/-8.18
      &mgr;g g(-1) (dry wt) of soil with OD(260)/OD(230) purity ratios between 0.80 and
      1.15. Analysis of sequence diversity in all extracts was conducted using PCR
      single strand conformation polymorphism (SSCP). Profiles generated using
      universal 16S rDNA primers (Com1/Com2) were found to be identical when used to
      amplify 16S rDNA extracted directly from soil. The genus Pseudomonas was targeted
      in order to reduce profile complexity, which was apparent when using universal
      16S rDNA primers, and which hindered direct comparison of sequence diversity. A
      Pseudomonas culture library and non-cultured Pseudomonas 16S rDNA genes were used
      to provide a background count of Pseudomonas operational taxonomic units present
      in the soil. Cloning and sequencing of amplicons generated using a Pseudomonas
      specific (Ps-for) and a universal 16S rDNA (Com2) primer, coupled with nested
      amplification (Com1/Com2 amplification from Ps-for/Ps-rev amplicons), used in
      conjunction with SSCP, revealed that environmental contaminants co-extracted with
      DNA, such as humic acid, significantly reduced primer specificity. SSCP was
      sensitive enough to reveal template bias in different primer sets. PCR
      restriction fragment length-SSCP of Pseudomonas 16S rDNA amplified from soil
      extracted DNA revealed distinct differences in sequence representation between
      extraction methods and showed that greater DNA yield is not synonymous with
      higher sequence diversity. We, therefore, suggest that DNA extractions from soil
      should be evaluated not only in terms of quantity and purity, but also in terms
      of the sequence diversity present. SSCP proved to be a valuable tool for the
      assessment of the methodologies commonly used in PCR-mediated microbial ecology
      studies.

PMID- 11451519
TI  - Multitude and temporal variability of ecological niches as indicated by the
      diversity of cultivated bacterioplankton.
AB  - The diversity of cultured planktonic bacteria was analyzed. Bacterial strains
      were isolated from a eutrophic lake (Zwischenahner Meer, Niedersachsen, Germany)
      at three different sampling dates (October 1997, April and May 1998).
      Phylogenetic diversity was assessed by polymerase chain reaction (PCR),
      denaturing gradient gel electrophoresis (DGGE), and sequencing of 16S rRNA gene
      fragments. Enterobacterial repetitive intergenic consensus (ERIC)-PCR revealed a
      high genomic diversity within the strain collections, which exceeded the
      diversity of the 16S rRNA gene sequences considerably. The composition of each of
      the three strain collections was unique since strains isolated at different dates
      always exhibited different ERIC-PCR fingerprints. Growth tests with 59 different
      carbon substrates demonstrated that even strains with identical ERIC-PCR
      fingerprints, isolated on one sampling date, differed in their physiology. The
      culturable fraction investigated in the present study constituted a relatively
      small fraction (</=15%) of the whole bacterioplankton assemblage. Nevertheless,
      the high physiological diversity in this fraction already indicates that a
      multitude of different ecological niches must exist in the planktonic
      environment. The majority of strains isolated in April prior to the decay of the
      phytoplankton bloom were members of the Cytophaga-Flavobacterium group. One month
      later, not a single strain of this group could be isolated. When a group-specific
      PCR-DGGE technique was employed, rapid shifts in the diversity of non-cultured
      Cytophaga-Flavobacteria also became evident. Based on the rapid shifts in the
      composition of cultivated as well as some non-cultivated bacteria, the ecological
      niches in the planktonic habitat must undergo rapid temporal changes.

PMID- 11451520
TI  - Use of 16S rRNA-targeted oligonucleotide probes to investigate the distribution
      of sulphate-reducing bacteria in estuarine sediments.
AB  - The distribution of sulphate-reducing bacteria (SRBs) in three anaerobic
      sediments, one predominantly freshwater and low sulphate and two predominantly
      marine and high sulphate, on the River Tama, Tokyo, Japan, was investigated using
      16S rRNA-targeted oligonucleotide probes. Hybridisation results and sulphate
      reduction measurements indicated that SRBs are a minor part of the bacterial
      population in the freshwater sediments. Only Desulfobulbus and Desulfobacterium
      were detected, representing 1.6% of the general bacterial probe signal. In
      contrast, the SRB community detected at the two marine-dominated sites was larger
      and more diverse, representing 10-11.4% of the bacterial signal and with
      Desulfobacter, Desulfovibrio, Desulfobulbus and Desulfobacterium detected. In
      contrast to previous reports our results suggest that Desulfovibrio may not
      always be the most abundant SRB in anaerobic sediments. Acetate-utilising
      Desulfobacter were the dominant SRB in the marine-dominated sediments, and
      Desulfobulbus and Desulfobacterium were active in low-sulphate sediments, where
      they may utilise electron acceptors other than sulphate.

PMID- 11451521
TI  - Gel sequestration of heavy metals by Klebsiella oxytoca isolated from iron mat.
AB  - The enterobacterium Klebsiella oxytoca strain BAS-10 was isolated from sediments
      under an iron mat formed in a stream receiving leached waters from pyrite mine
      tailings. Under anaerobic laboratory conditions, BAS-10 fermented Fe(III)-citrate
      and Na-citrate giving CH(3)COOH and CO(2). In the presence of ferric citrate, BAS
      10 secreted quantities of a thick gel containing glucose and/or mannose, if not
      other sugars. Sugar residues were observed in microbial aggregates using the
      sugar-specific concanavalin A lectin conjugated with fluorescein and imaged by a
      scanning confocal laser microscope. The gel bound Fe(III) which quickly
      precipitated. During fermentation, however, half the initial Fe(III)
      concentration was reduced to Fe(II) which did not bind to the gel and remained in
      solution. BAS-10 showed a high tolerance to heavy metals. Its growth was not
      inhibited by 1 mM Zn-, Pb- or Cd-acetate. These cations also co-precipitated with
      the iron gel, suggesting a possible application of this strain for abatement of
      toxic metals under anaerobic conditions.

PMID- 11451522
TI  - Structure and diversity of Gram-negative sulfate-reducing bacteria on rice roots.
AB  - Specific PCR assays were used to amplify the 16S rRNA genes of the
      Desulfobacteriaceae and the Desulfovibrionaceae from extracted environmental DNA
      from rice roots. 16S rDNA-based community patterns of the Desulfobacteriaceae
      were generated via terminal restriction fragment length polymorphism analysis
      from rice roots and compared with bulk soil. The molecular fingerprints showed no
      significant difference between rice roots and bulk soil, but changes during the
      vegetation period. 16S rDNA clone libraries and sequencing showed that the
      predominant terminal restriction fragments represented distinct phylogenetic
      groups. The 16S rDNA clone sequences of the Desulfobacteriaceae fell in the
      phylogenetic radiation of Desulfonema and Desulfosarcina or grouped within the
      Desulforhabdus-Syntrophobacter assemblage. Three of the latter sequences were
      closely affiliated with the MPN isolate EZ-2C2 from rice roots. All
      Desulfovibrionaceae 16S rDNA clone sequences, with one exception, were affiliated
      with the MPN isolate F1-7b from rice roots. The clustering of the clone sequences
      and the close phylogenetic affiliation with isolates from MPN enrichments from
      the same habitat in two cases indicated that these sequence clusters may
      represent predominant Gram-negative sulfate reducers on rice roots.
      Quantification of the bacterial abundances was accomplished by rRNA dot blot
      hybridization. In total the Gram-negative sulfate reducers accounted for
      approximately 2-3% of the total rRNA content. The relative rRNA abundance of the
      Desulfobacteriaceae was, at 1.4%, higher than that of the Desulfovibrionaceae
      (0.5%).

PMID- 11451523
TI  - Geographic distribution of Desulfitobacterium frappieri PCP-1 and
      Desulfitobacterium spp. in soils from the province of Quebec, Canada.
AB  - The presence of indigenous Desulfitobacterium species in 44 soil samples taken
      from various sites in the southern part of the province of Quebec (Canada) and
      four from locations outside Quebec was investigated. Twenty-four of these soils
      were sampled from contaminated industrial sites. Indigenous Desulfitobacterium
      bacteria from soil samples were enriched by cultivation in anaerobic soil slurry
      culture. Total DNA was then extracted from these slurries and polymerase chain
      reaction (PCR) amplifications were performed with primers targeting 16S ribosomal
      RNA gene sequences of Desulfitobacterium spp. and of Desulfitobacterium frappieri
      PCP-1. A positive PCR signal was obtained in 31 soil slurry cultures. Resolution
      of single-strand DNAs of some of the PCR products by a single-strand
      conformational polymorphism protocol suggests that more than one species of
      Desulfitobacterium were present in the corresponding slurry cultures. These
      results suggest that Desulfitobacterium are ubiquitous in soils in the province
      of Quebec, especially in soils from the St. Lawrence valley and the southern part
      of the province.

PMID- 11451524
TI  - Diversity of free-living prokaryotes from a deep-sea site at the Antarctic Polar
      Front.
AB  - To contribute to the understanding of deep-sea planktonic communities, we
      explored the prokaryotic diversity of a 3000 m deep site at the Antarctic Polar
      Front using molecular methods. Bacterial 16S rDNA-amplified sequences
      corresponded to the as yet uncultivated groups SAR11, within the alpha
      Proteobacteria, and SAR324, within the delta-Proteobacteria, as well as to the
      gamma-Proteobacteria, Cytophagales, Planctomyces, Gram-positives, and the group
      of environmental sequences SAR406. Among them, gamma-proteobacterial sequences
      were the most abundant and diverse. Within Archaea, and using six different
      primer sets for 16S rDNA amplification, only euryarchaeotal sequences were
      retrieved. Most of them clustered with the Thermoplasma-related marine groups II
      and III, but some corresponded to a recently described group of marine sequences
      emerging at the base of haloarchaea. Our data suggest that gamma-Proteobacteria
      and Euryarchaeota may be dominant elements in terms of genetic diversity of the
      two prokaryotic domains in this deep-sea pelagic area.

PMID- 11451525
TI  - Molecular diversity of arbuscular mycorrhizal fungi colonising arable crops.
AB  - We used differences in small subunit ribosomal RNA genes to identify groups of
      arbuscular mycorrhizal fungi that are active in the colonisation of plant roots
      growing in arable fields around North Yorkshire, UK. Root samples were collected
      from four arable fields and four crop species, fungal sequences were amplified
      from individual plants by the polymerase chain reaction using primers NS31 and
      AM1. The products were cloned and 303 clones were classified by their restriction
      pattern with HinfI or RsaI; 72 were subsequently sequenced. Colonisation was
      dominated by Glomus species with a preponderance of only two sequence types,
      which are closely related. There is evidence for seasonal variation in
      colonisation in terms of both level of colonisation and sequence types present.
      Fungal diversity was much lower than that previously reported for a nearby
      woodland.

PMID- 11451526
TI  - Isolation and characterisation of new Gram-negative and Gram-positive atrazine
      degrading bacteria from different French soils.
AB  - The capacity of 12 soils to degrade atrazine was studied in laboratory
      incubations using radiolabelled atrazine. Eight soils showed enhanced degradation
      of this compound. Twenty-five bacterial strains able to degrade atrazine were
      isolated by an enrichment method from 10 of these soils. These soils were chosen
      for their wide range of physico-chemical characteristics. Their history of
      treatment with atrazine was also variable. The genetic diversity of atrazine
      degraders was determined by amplified ribosomal restriction analysis (ARDRA) of
      the 16S rDNA gene with three restriction endonucleases. The 25 bacterial strains
      were grouped into five ARDRA types. By sequencing and aligning the 16S rDNA
      genes, the isolates were shown to belong to the Gram-negative species
      Chelatobacter heintzii, Aminobacter aminovorans, Stenotrophomonas maltophilia and
      to the Gram-positive genus Arthrobacter crystallopoietes. These species were not
      described previously as being capable of atrazine degradation. Most Gram-negative
      bacteria could mineralise (14)C ring labelled atrazine and carried the atzA,
      atzB, atzC and trzD genes. Gram-positive strains could convert atrazine to
      cyanuric acid and carried only the atzB and atzC genes. In this study, we
      describe the atrazine degradation capacities and corresponding genes in bacterial
      species that were not known as atrazine degraders. We report for the first time
      the occurrence of the trzD gene in these atrazine-mineralising bacteria and we
      demonstrate the potential use of colony hybridisation to isolate bacteria
      involved in atrazine degradation.

PMID- 11451527
TI  - Comparison of paralytic shellfish toxin (PST) production by the dinoflagellates
      Alexandrium lusitanicum NEPCC 253 and Alexandrium tamarense NEPCC 407 in the
      presence and absence of bacteria.
AB  - The ability of two Alexandrium species to produce paralytic shellfish toxins
      (PST) in laboratory culture following the generation of bacteria-free cultures
      was investigated. The dinoflagellates Alexandrium lusitanicum NEPCC 253 and
      Alexandrium tamarense NEPCC 407 were cultured in the presence of antibiotics and
      tested for residual bacteria. After treatment with a cocktail of streptomycin,
      ciprofloxacin, gentamicin and penicillin G, bacteria could not be detected in
      either of the treated Alexandrium cultures using 17 different solid and broth
      bacterial growth media, by epifluorescence microscopy with the dye Sybr green 1,
      or polymerase chain reaction amplification using universal eubacterial primers
      designed to target the 16S rRNA gene. Subsequent analysis of A. lusitanicum for
      PST using high performance liquid chromatography demonstrated that the growth
      rate and toxin profile remained similar in both bacteria-free and control
      cultures, although the quantity of toxins produced differed with the bacteria
      free culture producing generally more of each compound and also having a greater
      toxin content in terms of saxitoxin equivalents. A. tamarense also retained
      similarities between the bacteria-free and control cultures in terms of growth
      rates and toxin profile, although in this instance, depending on the growth stage
      and the toxin, the control culture produced more of some toxins than the bacteria
      free culture. The control culture was also more toxic in terms of saxitoxin
      equivalents than the axenic culture. These results suggest that bacteria can
      influence toxin production in laboratory cultures of Alexandrium species although
      the mechanisms remain unknown.

PMID- 11451528
TI  - Evidence for the presence of thermophilic Fe(III)-reducing microorganisms in deep
      sea hydrothermal vents at 13 degrees N (East Pacific Rise).
AB  - Microorganisms capable of dissimilatory Fe(III) reduction in the temperature
      range of 52-90 degrees C were enriched from outer and inner parts of chimney-like
      structures, tubes of the polychaetous annelid Alvinella sp., and hydrothermal
      fluids collected at 13 degrees N hydrothermal vent sites on the East Pacific Rise
      at a depth of 2650 m. Numbers of culturable Fe(III)-reducing thermophiles
      estimated by the serial dilution technique varied from 10 to 10(7) cells per
      cm(3) of sample. Phylogenetic analysis of bacterial and archaeal PCR-amplified
      16S rDNA genes obtained from Fe(III)-reducing enrichments and separated by
      denaturing gradient gel electrophoresis revealed sequences related to
      Deferibacter, Thermotogales (Bacteria) and Thermococcus (Archaea) for which the
      capacity for Fe(III) reduction had been reported. This was confirmed by isolating
      a hyperthermophilic iron reducer that belongs to the genus Thermococcus. Other
      bacterial thermophiles found in the enrichments were related to so far uncultured
      members of the Clostridiaceae, and epsilon-subdivision of the Proteobacteria.

PMID- 11451529
TI  - Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase.
AB  - There is an urgent need for the development of new drugs to treat Chagas'
      disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme
      dihydrofolate reductase (DHFR) has been a very successful drug target in a number
      of diseases and we decided to investigate it as a potential drug target for
      Chagas' disease. A homology model of the enzyme was used to search the Cambridge
      Structural Database using the program DOCK 3.5. Compounds were then tested
      against the enzyme and the whole parasite. Compounds were also screened against
      the related parasite, Trypanosoma brucei.

PMID- 11451530
TI  - Imidazo-thiazine, -diazinone and -diazepinone derivatives. Synthesis, structure
      and benzodiazepine receptor binding.
AB  - In our search for new compounds acting on benzodiazepine receptors among the
      fused 2-thiohydantoin derivatives, a series of arylidene imidazo[2,1-b]thiazines
      was synthesized. The 1,2- and 2,3- cyclized derivatives of mono- and di
      substituted Z-5-arylidene-2-thiohydantoins were examined (the X-ray crystal
      structure of Z-2-cinnamylidene-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3(2H)
      one was determined) and compared with the diphenyl derivatives. To investigate
      the influence of the type of annelated ring on the biological activity,
      imidazo[2,1-b]pyrimidinone and imidazo[2,1-b]diazepinone derivatives were
      obtained. The method used in annelation (1,2- and 2,3-cyclized isomers with the
      exception of fused arylidene imidazothiazines), the substitution pattern
      (arylidene towards diphenyl) as well as the character of the annelated ring had
      minor influence on the benzodiazepine receptor affinity of the investigated
      compounds. It appears that the greatest influence on the biological activity has
      the character and position of the substituents on the arylidene ring.

PMID- 11451531
TI  - Synthesis of some 1-(2-naphthyl)-2-(imidazole-1-yl)ethanone oxime and oxime ether
      derivatives and their anticonvulsant and antimicrobial activities.
AB  - In this study, oxime and oxime ether derivatives of anticonvulsant nafimidone [1
      (2-naphthyl)-2-(imidozole-1-yl)ethanone] were prepared as potential
      anticonvulsant compounds. Nafimidone oxime was synthesized by the reaction of
      nafimidone and hydroxylamine hydrochloride. O-Alkylation of the oxime by various
      alkyl halides gave the oxime ether derivatives. Anticonvulsant activity of the
      compounds was determined by maximal electroshock (MES) and subcutaneous metrazole
      (scMet) tests in mice and rats according to procedures of the Antiepileptic Drug
      Development (ADD) program of the National Institutes of Health (NIH). In addition
      to anticonvulsant evaluation, compounds were also screened for possible
      antibacterial and antifungal activities because of the structural resemblance to
      the azole antifungals, especially to oxiconazole. All compounds were evaluated
      against three human pathogenic fungi and four bacteria using the microdilution
      method. Most of the compounds exhibited both anticonvulsant and antimicrobial
      activities; the O-alkyl substituted compounds (2, 3, 4 and 5) were found to be
      more active than the O-arylalkyl substituted compounds in both screening
      paradigms.

PMID- 11451532
TI  - Syntheses and immunomodulatory activity of 3-O-[2'-hydroxy-3'-N,N-disubstituted
      aminopropan-1'-yl]-alpha-D-glucofuranoses.
AB  - A number of 3-O-[2'-hydroxy-3'-N,N-aminopropan-1'-yl]-alpha-D-glucofuranoses were
      synthesised by regioselective oxirane ring opening in compound 2 with different
      secondary amines followed by selective deacetalisation. All the compounds were
      tested for their immunomodulatory potential in vitro; seven of them expressed
      significant immunostimulant activity.

PMID- 11451533
TI  - Stereospecific synthesis and biological evaluations of beta-L
      pentofuranonucleoside derivatives of 5-fluorouracil and 5-fluorocytosine.
AB  - In the search for new chemotherapeutic agents, we have focused our work on the
      synthesis and the study of several unnatural beta-L-nucleoside analogues. In this
      paper, we report on the synthesis of beta-L-pentofuranonucleosides (and their 2'
      deoxy derivatives) of 5-fluorouracil and their inhibitory effects on the
      proliferation of several murine and human tumor cells. The corresponding 5
      fluorocytosine derivatives were also synthesized and their anti-HIV and anti-HBV
      activities have been evaluated.

PMID- 11451534
TI  - Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of
      carbocyclic derivatives of distamycin with chlorambucil moiety.
AB  - New carbocylic analogues of distamycin and netropsin with chlorambucil moieties 5
      8 have been synthesised. Data from the ethidium displacement assay showed that
      these compounds bind in the minor groove of DNA. The observed reduced affinity to
      AT pairs and increased affinity towards GC sequences of the carbocyclic
      lexitropsins with chlorambucil moiety 5-8 in comparison with netropsin and
      distamycin was observed and rationalised by means of molecular modelling
      techniques. All of the compounds 5-8 showed antiproliferative and cytotoxic
      effects in the standard cell line of the mammalian tumour MCF-7.

PMID- 11451535
TI  - Synthesis and cytotoxicity of artemisinin derivatives containing cyanoarylmethyl
      group.
AB  - A series of 12alpha-deoxoartemisinyl cyanoarylmethyl dicarboxylates (4a-4o),
      dicarboxylic acids 12alpha-deoxoartemisinyl ester cyanoarylmethyl amide (5a-5k),
      and dicarboxylic acids 12alpha-deoxoartemisinyl ester N-methylcyanoarylmethyl
      amide (6a-6l), showing moderate cytotoxicity against P388 and L1210 cells were
      prepared. They induced the significant accumulation of L1210 and P388 cells in
      the G1 phase of the cell cycle. This mechanism of action was quite different from
      that of the majority of cytotoxic compounds used in the chemotherapy of cancer.
      Compound 4b possessed better cytotoxicity than the other compounds.

PMID- 11451537
TI  - Calcium channel blockers in the management of preterm labor and hypertension in
      pregnancy.
AB  - Calcium channel blockers (CCBs) have the ability to inhibit contractility in
      smooth muscle cells. CCBs have an already established role in the treatment of
      non-pregnant hypertension and angina pectoris. Some epidemiological studies found
      an association between the use of CCBs and an increase in cardiovascular
      mortality, malignancy, and gastrointestinal bleeding. More recent studies with
      many more patients and a longer follow-up did not find these associations. In
      obstetrics CCBs have become increasingly popular for the management of preterm
      labor and pregnancy-induced hypertensive disorders. Meta-analysis shows that use
      of nifedipine in comparison with betamimetics is associated with a more frequent
      successful prolongation of pregnancy in case of preterm labor, resulting in
      significantly fewer admissions of newborns to the neonatal intensive care unit
      (NICU), and is associated with a lower incidence of respiratory distress
      syndrome. No adverse fetal side effects in humans have been reported with the use
      of nifedipine for obstetric indications. Nifedipine is an effective and safe drug
      to use when tocolytic therapy is indicated for preterm labor. In preeclampsia
      nifedipine effectively lowers blood pressure and can be a good alternative for
      (di) hydralazine.

PMID- 11451538
TI  - Comparison study between induced and spontaneous term and preterm births of small
      for-gestational-age neonates.
AB  - OBJECTIVE: To compare perinatal and maternal outcome between induced and
      spontaneous small-for-gestational-age (SGA) neonates at term and preterm
      deliveries. STUDY DESIGN: A cross-sectional study was designed and two groups
      were identified at each gestational age: study group - SGA neonates born after
      induction of labor, comparison group - SGA neonates born after spontaneous onset
      of labor. SGA was decoded as birth weight below 10th percentile. The population
      consisted of 367 consecutive SGA singleton preterm neonates (24-36 weeks'
      gestation) and 3921 term SGA neonates (37-42 weeks' gestation) delivered between
      1990 and 1997. Patients with antepartum death and congenital anomalies were
      excluded from this study. RESULTS: The prevalence of SGA neonates among preterm
      deliveries was significantly higher than among term deliveries (9.3 versus 6.1%,
      P<0.001). The rate of induction of labor among preterm SGA deliveries was
      significantly higher than term SGA deliveries (17.7 versus 13.4%, P=0.002). The
      rates hypertensive disorders, suspected IUGR, placental abruption, cesarean
      section, chorioamnionitis and endometritis were significantly higher among
      preterm SGA than in term SGA. A multiple logistic regression analysis
      demonstrated that suspected IUGR, severe PIH (but not mild PIH), chronic
      hypertension and placental abruption were independent risk factors for induction
      of labor among preterm SGA neonates. In addition to these factors,
      oligohydramnios was considered to be an independent risk factor only among term
      SGA. No significant differences were found in the mean birthweight and post
      partum death rates between the induced and spontaneous preterm and term SGA. The
      incidence of Apgar score < 7 at 5 min was significantly lower only among induced
      term SGA. CONCLUSIONS: Induction of labor in preterm SGA neonates is performed
      mainly due to maternal severe hypertension disorders. The indications for
      induction of labor among term SGA include maternal hypertensive disorders (mild
      or severe) as well as neonatal status, represented mainly by oligohydramnios. In
      addition, induction of labor in preterm or term SGA neonates does not change
      neonatal outcome. Moreover, since no evidence of improved neonatal outcome was
      demonstrated in either indicated group, preterm or term, the question of timing
      and indications for induction of labor should be discussed.

PMID- 11451539
TI  - Changes in the rate of tubal ligation done after cesarean section.
AB  - OBJECTIVE: We studied tubal ligations done after cesarean section in a Spanish
      hospital during a 20-year period, in order to analyze changes in patient
      characteristics and indications for cesarean delivery. STUDY DESIGN: We reviewed
      the clinical records, for the period from 1978 to 1997, of 1996 cases of cesarean
      section followed by tubal ligation in 108776 births in which the fetus weighed
      1000 g or more. RESULTS: During the 20-year period of study, the proportion of
      cesarean sections relative to vaginal deliveries increased, as did the frequency
      of cesarean section followed by tubal ligation relative to cesarean and vaginal
      deliveries. The proportion of women who underwent tubal ligation after a second
      cesarean section decreased from 60% during 1978-1982 to 5.6% during 1993-1997.
      The most frequent maternal pathology associated with gestation was previous
      cesarean section (60.5%), although 50% of the women had no underlying pathology.
      CONCLUSIONS: In our setting, the rate of cesarean section followed by tubal
      ligation has been increasing steadily since the early 1980s. The proportion of
      women who requested tubal sterilization and who had only one living child, or who
      had had a previous cesarean birth, also increased.

PMID- 11451540
TI  - Factors associated with vaginal birth after cesarean in a maternity hospital of
      Rio de Janeiro.
AB  - OBJECTIVES: Identifying characteristics associated with vaginal birth after
      cesarean. STUDY DESIGN: Case-control study based on medical records. STUDY
      POPULATION: women with previous cesarean, who had delivered in a public Rio de
      Janeiro maternity hospital between 1992 and 1996. SAMPLE: 141 cases (vaginal
      births after cesarean) and 304 controls (a new cesarean after other(s)).
      Multivariate analysis with logistic regression was carried out. RESULTS: The
      following characteristics were associated with greater probability of vaginal
      birth (IC=95%): only one previous cesarean (OR=19.05; IC=6.88-52.76); cervical
      dilatation at admission above 3 cm (OR=8.86; IC=4.93-15.94); gestational age
      below 37 weeks (OR=3.01; IC=1.40-6.46); history of at least one previous vaginal
      birth (OR=2.12; IC=1.18-3.82); level of education below high school (OR=1.94;
      IC=1.02-3.69). Chronic hypertension reduced the chances of vaginal birth
      (OR=0.44; IC=0.22-0.88). CONCLUSIONS: Among the factors that can be modified to
      reduce the number of repeated cesareans are: trial of labor promotion, reducing
      admission of women at early stages of labor and adequate hypertension management
      during pregnancy. CONDENSATION: Among the factors that can be modified to reduce
      the number of repeated cesareans are: the trial of labor promotion for women who
      present previous cesarean, reducing admission of women at early stages of labor
      and adequate hypertension management during pregnancy.

PMID- 11451541
TI  - Lessons from Holland: hospital visiting as an instrument to assess the quality of
      obstetric and gynecological care.
AB  - OBJECTIVE: to assess and improve the quality of hospital based obstetric and
      gynecological care. STUDY DESIGN: in 1991 a hospital visiting scheme by peers was
      launched by the Dutch Society of Obstetrics and Gynecology. The present study
      gives a full description of the scheme and its potential impact on the quality of
      obstetric and gynecological care in all of the group practices in non-teaching
      hospitals in the Netherlands (n=87). Comprehensive and multifaceted assessment
      was done in a standardised way, thereby focusing on the process of care rather
      than health care outcome. Following each visitation by an ad hoc visiting
      committee, consisting of three experienced gynecologists, the plenary visitation
      committee issues a formal report to the participating obstetric and gynecological
      centre. Apart from the condensed summary of the findings of the visiting
      committee during the 1 day visit, the report contains recommendations for the
      improvement of obstetric and gynecological care. RESULTS: problems most commonly
      encountered during visits were in the areas of communication. Other problem areas
      frequently encountered include deficient medical record keep and lack of
      adherence to the standards for postgraduate education. CONCLUSIONS: given the
      willingness of gynecologists to participate in a constructive way and their
      readiness to comply with the recommendations, it is concluded that formal
      visiting could provide an important means of improving obstetric and
      gynecological care in a hospital setting.

PMID- 11451542
TI  - Increase of endothelial nitric oxide synthase and endothelin-1 mRNA expression in
      human placenta during gestation.
AB  - OBJECTIVE: To investigate the maturation of the paracrine system's endothelial
      nitric oxide synthase (eNOS), inducible NOS (iNOS), endothelin-1 (ET-1) and
      adrenomedullin (AM) in human placenta during the 2nd and 3rd trimester of
      pregnancy. STUDY DESIGN: Placental tissue from 14 healthy women with normal
      pregnancy and from 13 patients giving birth to premature infants following
      premature labor was obtained. Messenger RNA expression was determined using
      quantitative TaqMan real-time PCR. RESULTS: Placental eNOS/GAPDH and ET-1/GAPDH
      mRNA expression significantly increased as a function of gestational age (r=0.63,
      P<0.001 and r=0.53, P=0.007, respectively). There was no change in gene
      expression of neither iNOS nor AM mRNA/GAPDH during gestation (r=0.02, P=0.75 and
      r=0.001, P=0.99, respectively). CONCLUSION: There is a maturation of eNOS and ET
      1 in human placenta with gestation reflecting developmental changes of important
      paracrine endothelial and trophoblastic regulators. AM and iNOS show no
      maturation during pregnancy.

PMID- 11451543
TI  - Prognostic value of repeated serum CA 125 measurements in first trimester
      pregnancy.
AB  - OBJECTIVE: To assess the diagnostic value of maternal CA 125 in patients with
      symptomatic first trimester pregnancy and to evaluate the prognostic significance
      of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat,
      complicated by vaginal bleeding. STUDY DESIGN: Two prospective open-label studies
      with longitudinal follow-up in the second trial. SETTING: Academic Department of
      Obstetrics and Gynecology, University of Cologne. PATIENTS: Study 1: 168 patients
      presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29;
      missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33;
      and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2:
      Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12
      all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted
      whereas the remainder had normally continuing pregnancy until term. MAIN OUTCOME
      MEASURE: Study 1: Single serum determinations of CA 125 and beta-hCG were
      correlated with the different disorders observed. Study 2: Two sequential
      measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval
      were related to the outcome of pregnancy as indicated by changes of the
      ultrasound presentation, miscarriage, future hospitalization, or delivery.
      RESULTS: Study 1: Patients with vaginal bleeding generally had higher median CA
      125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8
      IU/ml; range 1.0-157). No statistically significant differences in regard to
      median serum CA 125 levels between symptomatic and normal pregnancies occurred:
      normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range
      1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml
      (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial
      CA 125 levels did not differ significantly between both groups of patients with
      27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml.
      After 5-7 days, CA 125 in all patients who eventually aborted remained high or
      increased whereas non-aborters all had constantly low or steeply declining CA 125
      measures. beta-hCG increased in all non-aborters but also in 13/18 aborters
      during the 5-7 day interval. CONCLUSION: Single serum measurements of CA 125 in
      symptomatic first trimester pregnant patients failed to discriminate spontaneous
      abortion, ectopic or normal pregnancies. However, sequential determinations of
      maternal CA 125 measurements appear to be a highly sensitive prognostic marker in
      patients with viable pregnancy at risk for abortion.

PMID- 11451544
TI  - Combined heterozygosity for methylenetetrahydrofolate reductase (MTHFR) mutations
      C677T and A1298C is associated with abruptio placentae but not with intrauterine
      growth restriction.
AB  - OBJECTIVE: This study was undertaken to investigate the involvement of MTHFR gene
      mutations C677T and A1298C implicated in vascular disease, in patients with
      abruptio placentae and intrauterine growth restriction (IUGR). STUDY DESIGN: DNA
      was extracted from blood samples of 54 patients with placental vasculopathy (18
      patients with abruptio placentae and 36 with IUGR) and 114 control patients and
      amplified by the polymerase chain reaction (PCR). The resulting fragments were
      subjected to restriction enzyme analysis and resolved by gel electrophoresis.
      RESULTS: A significant association could be demonstrated between mutation A1298C
      and both abruptio placentae and IUGR. Combined heterozygosity for mutations C677T
      and A1298C was detected in 22.2% of abruptio placentae cases. CONCLUSIONS:
      Combined heterozygosity for MTHFR mutations C677T and A1298C may represent a
      genetic marker for abruptio placentae.

PMID- 11451545
TI  - Fetal habituation to vibroacoustic stimulation in uncomplicated postterm
      pregnancies.
AB  - OBJECTIVES: Testing of fetal habituation to repeated vibroacoustic stimulation
      might give additional information concerning the fetal condition and central
      nervous system (CNS) functioning in postterm pregnancies. This study is designed
      to investigate whether healthy postterm fetuses are able to habituate and if so,
      if the habituation pattern of postterm fetuses differs from that of term fetuses.
      STUDY DESIGN: Twenty women with an uncomplicated pregnancy beyond 41 weeks
      gestational age (GA) participated, and 37 women with a GA between 37 and 40 weeks
      served as controls. The vibroacoustic stimulus was repeatedly applied to the
      maternal abdomen above the fetal legs for a period of 1s every 30s. A fetal trunk
      movement within 1s of stimulus application was considered a positive response.
      Lack of response to four consecutive stimuli indicated habituation. The
      habituation rate is defined as the number of stimuli applied before the fetus
      stopped responding. Data were compared using Mann-Whitney U test. RESULTS: Of the
      18 postterm fetuses in which the presence or absence of habituation could be
      established, 14 habituated and four persisted in responding. Twenty-six of the 32
      term fetuses, in which the presence or absence of habituation could be
      established, habituated and six persisted in responding. The habituation rate
      varied widely in postterm (median of eight stimuli, quartile ranges of 6 and 18)
      as well as in term fetuses (median of 9.5 stimuli, quartile ranges of 6 and 15).
      There was no difference in median habituation rate between postterm and term
      fetuses. CONCLUSION: The ongoing maturation of the CNS in the last weeks of
      pregnancy appears not to be reflected in the fetal habituation pattern.
      Furthermore, the interfetal variability in habituation of healthy postterm
      fetuses is such that testing of habituation appears not to be suitable for the
      identification of the fetus at risk for an adverse neonatal outcome.

PMID- 11451546
TI  - Extra-amniotic Foley catheter and prostaglandin E(2) gel for cervical ripening at
      term gestation.
AB  - OBJECTIVE: This study evaluated the efficacy of intravaginal prostaglandin E(2)
      gel in comparison with that of a Foley catheter for cervical ripening and
      induction of labor. STUDY DESIGN: Consecutive patients with unfavorable cervix
      requiring preinduction cervical ripening and induction of labor at term gestation
      were asked to participate in the study. One hundred and two patients were
      assigned to treatment with intravaginal prostaglandin E(2) gel (group 1) and 122
      patients underwent the placement of an intracervical Foley catheter (group 2).
      After a maximum of three applications of intravaginal prostaglandin E(2) gel
      (18h) or after 18h from Foley catheter insertion oxytocin was administered to
      patients not in active labor. Labor profiles and pregnancy and neonatal outcome
      were compared between groups. RESULTS: The groups were comparable in term of
      demographic characteristics, indications for induction of labor, Bishop score at
      admission. The induction to labor time and the induction to delivery time were
      similar between groups. The cesarean sections rate was higher in group 1 than in
      group 2 (26.5 versus 14.7%, P<0.05). This remained significant when the analysis
      was restricted to nulliparous patients (32.3 versus 14.2%). The incidence of
      urinary tract infections, chorioamnionitis, and febrile morbidity was similar
      between groups. CONCLUSION: For preinduction cervical ripening, the Foley
      catheter is a valid alternative to the application of intravaginal prostaglandin
      E(2) gel and it is associated with a lower cesarean rate in nulliparous women.

PMID- 11451547
TI  - Augmentin treatment during pregnancy and the prevalence of congenital
      abnormalities: a population-based case-control teratologic study.
AB  - OBJECTIVE: To study the human teratogenic potential of augmentin
      (amoxicillin+clavulanic acid) treatment during pregnancy. MATERIALS AND METHODS:
      Pair analysis of cases with different congenital abnormalities and their matched
      controls in the population-based dataset of the Hungarian Case-Control
      Surveillance of Congenital Abnormalities, between 1991 and 1996. RESULTS: The
      case group included 6935 pregnant women who had offspring with congenital
      abnormalities, while the control group consisted of 10,238 pregnant women who had
      babies without any defects. The number (and rate) of pregnant women with
      augmentin treatment was 52 (0.75%) and 56 (0.55%) in the case and control groups,
      respectively (crude odds ratio (OR) with 95% confidence interval (CI) was 1.4,
      0.9-2.0). The comparison of augmentin treatments during the second-third months
      of pregnancy (i.e. in the critical period for most major congenital
      abnormalities) in case-control pairs did not show a higher use of augmentin in
      any congenital abnormality group. CONCLUSION: Augmentin treatment of pregnant
      women in usual therapeutic doses is unlikely to increase the risk of congenital
      abnormalities in newborn infants. However, the number of cases and controls was
      limited, therefore, further multicenter-multinational studies are needed for the
      final risk assessment.

PMID- 11451548
TI  - Follicular growth in fresh and cryopreserved human ovarian cortical grafts
      transplanted to immunodeficient mice.
AB  - OBJECTIVE: To investigate follicle growth in fresh and cryopreserved human
      ovarian cortical grafts transplanted to immunodeficient mice. STUDY DESIGN: Fresh
      or frozen-thawed human ovarian cortex was grafted subcutaneously or under the
      kidney capsule of 43 mice (35 nude mice and eight SCID mice), 14 of which were
      non-stimulated controls, 21 injected intra-peritoneally with gonadotrophins
      during 2 weeks and eight injected during 3 months. Follicle count was compared by
      Chi-square. RESULTS: Proportions of primordial follicles were significantly lower
      in grafts than in the tissue before transplantation in gonadotrophin-stimulated
      mice (37% versus 79%), but not in non-stimulated mice (51% versus 74%).
      Proportions of primary and secondary follicles were increased after
      transplantation indicating early follicular growth. One antral follicle was
      observed in a graft in a mouse stimulated for 3 months. CONCLUSION: Primordial
      follicles in fresh or frozen-thawed human ovarian cortex transplanted under the
      kidney capsule or subcutaneously can grow and are responsive to hormonal
      stimulation. CONDENSATION: Primordial follicles in fresh and cryopreserved human
      ovarian cortical grafts can initiate growth after transplantation to
      immunodeficient mice

PMID- 11451549
TI  - Gonadotropin-releasing hormone antagonist protocol: a novel method of ovarian
      stimulation in poor responders.
AB  - OBJECTIVE: To estimate the efficacy of gonadotropin-releasing hormone (GnRH)
      antagonist 'Cetrorelix' in poor responders comparing with the standard long
      protocol. DESIGN: The study population consisted of 21 poor responders who
      underwent ICSI and treated with Cetrorelix according to the multiple-dose
      protocol and who were compared with 21 poor responders treated according to the
      long protocol and who also underwent ICSI. Patients in both groups were matched
      for chronological age, the number of follicles found by ultrasound at the
      retrieval day and cause of infertility. Fifteen patients of GnRH antagonist group
      were treated with the combination of GnRH antagonist with clomiphene citrate (CC)
      plus gonadotropins, while six patients were treated with the combination of GnRH
      antagonist plus gonadotropins, but without CC. RESULTS: The use of GnRH
      antagonist in a multiple dose protocol gave a pregnancy rate of 14.28% which was
      in the range expected for patient with poor response, but with shorter treatment
      duration and with fewer ampoules of gonadotropins as compared with the use of a
      GnRH agonist protocol in a depot formulation. Within Cetrorelix group patients
      who received CC had a significant shorter duration of stimulation and needed
      fewer ampoules as compared with patients in the same group who did not receive
      CC. CONCLUSIONS: A GnRH antagonist multiple dose protocol may be the protocol of
      choice for the treatment of poor responders. The use of GnRH antagonist
      Cetrorelix ended with significantly less ampoules of gonadotropins and a shorter
      duration of stimulation.

PMID- 11451550
TI  - Combined approach as an effective method in the prevention of severe ovarian
      hyperstimulation syndrome.
AB  - The purpose of this study was to evaluate the effectiveness of combined approach
      on the prevention of severe ovarian hyperstimulation syndrome (OHSS) in high risk
      patients undergoing controlled ovarian hyperstimulation for IVF. The combined
      approach consisted of: (1) step-down administration of gonadotropins; (2)
      lowering the dose of human chorionic gonadotropin; (3) intravenous albumin
      infusion at the time of oocyte retrieval and (4) progesterone use for luteal
      support. Total of 87 high risk patients with a serum estradiol level >11,010
      pmol/l or 3000 pg/ml on HCG day were managed by this combined approach and their
      results were compared with 274 low risk patients. In all high risk patients, the
      gonadotrophin dose were decreased starting as early as on day 4 of ovarian
      stimulation as necessary, ovulation was triggered by a decreased HCG dose of 5000
      7000 IU according to the level of estradiol, intravenous infusion of 20% human
      albumin, 50-100ml were given just 1h before the oocyte retrieval and luteal
      support was provided either by 50mg progesterone in oil, IM or 600 mg micronized
      progesterone orally or vaginally until the day of beta-HCG determination. All
      patients were followed by serial ultrasonographic examinations and complete blood
      count analysis after embryo transfer to detect the early signs of OHSS and to
      allow early intervention. Age and duration of infertility were similar in both
      groups. Although the number of gonadotrophin ampoules used (22.7 +/- 4.7 versus
      27.8+/-3.7; P<0.05) was significantly lower, estradiol levels (16,764 +/- 6936
      pmol/l versus 8870 +/- 2456 pmol/l; P<0.05) and mean number of oocytes (18.3 +/-
      5.9 versus 10.6+/-5.4; P<0.05) were significantly higher in study group. There
      was no significant difference between groups in terms of the mean number of
      transferred embryos (3.2 +/- 1.1 versus 3.4+/-1.1) and rate of pregnancies (50.5%
      versus 40.1%). There was only one moderate and no severe OHSS case in the high
      risk group, while five moderate and one severe OHSS cases developed in the
      control group consisting of low risk patients. In conclusion, intravenous albumin
      combined with low dose HCG, early step-down administration of gonadotropins and
      progesterone use for luteal support, so called combined approach, proved to be
      effective in the prevention of severe ovarian hyperstimulation syndrome in
      documented high risk patients.

PMID- 11451551
TI  - Anatomic study of arcus tendineus fasciae pelvis.
AB  - OBJECTIVE: To describe the anatomy of the arcus tendineus fasciae pelvis.
      MATERIAL AND METHODS: Two fixed female cadaver pelvises (88 and 66 years old)
      were dissected. RESULTS: The arcus tendineus fasciae pelvis is a 10-cm-long
      fibrous thickening of the pelvic fascia which is medial to the obturator internus
      muscle and lateral to the peritoneum. It is inserted on the ischiatic spine and
      courses downward and anteriorly to the pubovesical ligament. The posterior third
      of the arcus tendineus fasciae pelvis is fused with the posterior third of the
      arcus tendineus musculus levatoris ani, forming a curve with upward and anterior
      concavity. This portion of the arcus tendineus is thick and easy to recognise
      upon palpation. It is located 1cm slightly above and anterior to the ischiatic
      spine and 2 cm from of the pudendal vessels, which course around the posterior
      inferior margin of the ischiatic spine. The superior margin of the median part of
      the arcus tendineus fasciae pelvis is crossed laterally by vessels for the
      obturator internus muscle arising from the internal iliac vessels. CONCLUSION: In
      genital prolapse cure, sutures must be placed through the anterior or median
      parts of the arcus tendineus fasciae pelvis. In any case, they must remain
      anterior to the posterior part of the arcus tendineus fasciae pelvis to avoid
      injury to the pudendal vessels.

PMID- 11451552
TI  - Endometrial biopsy during outpatient hysteroscopy: evaluation and comparison of
      two devices.
AB  - OBJECTIVE: Association of office hysteroscopy with outpatient endometrial biopsy
      is interesting to evaluate correctly endometrium. Purpose of this study was to
      evaluate and compare two endometrial biopsy devices during outpatient
      hysteroscopy, based on effectiveness and tolerance of the procedure. STUDY
      DESIGN: A single blind, randomised prospective study. RESULTS: 200 patients were
      randomised into two groups following outpatient hysteroscopy: 100 were biopsied
      with Vacurette and 100 biopsed with Pipelle. Pipelle was less painful compared to
      Vacurette (1.1+0.2 versus 1.6+0.3; P<0.001), no matter hormonal status (1+0.3
      versus 2+0.6; P<0.001 in premenopausal subgroup and 1+0.3 versus 1.4+0.3; P<0.001
      in postmenopausal subgroup). Vacurette was more effective than Pipelle (64/100
      versus 48/100; P=0.02), in case of normal or hypertrophic endometrium (56/72
      (77%) versus 40/65 (61%); P=0.04) but not in case of atrophic endometrium (8/28
      (29%) versus 8/35 (23%); P=0.6). Among the 112 patients with adequate sample,
      histologic results were normal, except for three cases of endometrial
      hyperplasia. Among the 88 patients with inadequate sample, 47 (53%) presented an
      atrophic endometrial aspect at hysteroscopy, whereas 41 (47%) were considered as
      normal. CONCLUSIONS: Vacurette was more effective though more painful than
      Pipelle. Both instruments were, however, well tolerated. Both instruments were
      not very effective in case of atrophic endometrium. Outpatient hysteroscopy
      combined with endometrial biopsy may help avoid further investigations.

PMID- 11451553
TI  - The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and
      angiogenesis) in invasive cervical cancer.
AB  - OBJECTIVE: The present study was designed to analyse the relationship between
      apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53,
      proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and
      angiogenesis in cervical cancer and their impact on clinical outcome. STUDY
      DESIGN: Tumours from 111 patients were assessed by immunohistochemistry for the
      expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for
      the quantification of the mitotic index and the microvessel density (CD 31). The
      results were correlated with various histopathologic characteristics and
      survival. RESULTS: The multiple Cox's regression analysis for overall survival of
      all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular
      permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO
      stage (P=0.070). Subanalysis was performed for the patients where the lymph node
      status was known (n=79). Adding the lymph node status gave as best model for
      overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic
      index (P=0.044). However, they hardly influenced the association. CONCLUSION: In
      the apoptotic pathway of cervical cancer, bcl-2 is one of most important
      proteins. It can probably not only mediate cell death but also regulate cell
      growth. A better understanding of their relations will probably provide the basis
      for more rational cancer therapies in the future.

PMID- 11451554
TI  - Psammomacarcinoma of the peritoneum.
AB  - Psammomacarcinoma is a rare histologic subtype of serous carcinoma originating in
      the ovary or peritoneum, characterized by massive psammoma body formation,
      invasiveness, and low-grade differentiation. Its clinical behavior appears
      similar to that of serous borderline tumors rather than that of typical invasive
      serous carcinomas. Peritoneal psammomacarcinoma is even rarer than its ovarian
      counterpart with only 10 cases have previously been documented in the literature.
      A case of F.I.G.O. stage IIIC peritoneal psammomacarcinoma is described. Optimal
      debulking surgery, including omentectomy, total abdominal hysterectomy, bilateral
      adnexectomy, and resection of segment of jejunum, was performed. The patient
      received adjuvant chemotherapy with taxol and cisplatin, and to date, 15 months
      after surgery, she is alive and with no evidence of disease. It is concluded that
      peritoneal psammomacarcinoma is a very rare tumor that behaves less aggressively
      than typical serous carcinoma. The mainstay of treatment is surgical debulking.
      The role of adjuvant chemotherapy has as yet not been established.

PMID- 11451555
TI  - Lymphoma-like lesion of the uterine cervix.
AB  - Lymphoma-like lesion of the uterine cervix is a benign reactive lymphoid
      hyperplasia associated with chronic cervicitis that may pose a problem in
      differential diagnosis from malignant lymphoma. It is a rare entity and only
      about 20 cases have been reported in the world literature. Two cases of cervical
      lymphoma-like lesion are described. In both patients, the diagnosis was based on
      microscopic examination of biopsies taken from the uterine cervix. One patient
      subsequently had a cervical conization that confirmed the diagnosis of lymphoma
      like lesion. Both patients are well, alive and with no evidence of malignant
      lymphoma. It is concluded that the diagnosis of lymphoma-like lesion is based on
      the well-established characteristic microscopic features of this lesion.
      Immunohistochemical staining is usually not helpful in distinguishing this lesion
      from malignant lymphoma. No specific treatment is necessary for this condition.

PMID- 11451556
TI  - Ectopic hydronephrotic kidney masquerading as an ovarian cyst during pregnancy.
AB  - An ectopic iliopelvic kidney with hydronephrosis causing fetal malpresentation is
      a rare occurrence. We describe this case for its unusual presentation which was
      mistaken for an ovarian cyst. The difficulty in diagnosis and the need for a high
      index of suspicion is highlighted.

PMID- 11451557
TI  - Three primary malignancies related to BRCA mutation successively occurring in a
      BRCA1 185delAG mutation carrier.
AB  - The 185delAG and 5382insC mutations in the BRCA1 gene and the 6174delT mutation
      in the BRCA2 gene (the Ashkenazi mutations) have been found to be significantly
      more common among Jews of eastern European ancestry (1 in 40, 2.5%) in comparison
      to the general population (1 in 800 to 1 in 300, 0.12-0.33%). Carriers of these
      mutations, especially the BRCA1 185delAG mutation, have a significantly increased
      lifetime risk of breast and ovarian carcinoma and other carcinomas as compared to
      non-carriers. A case of three primary malignancies related to the BRCA1 185delAG
      mutation successively occurring in a carrier of this mutation, is described. The
      patient successively developed breast carcinoma, ovarian micropapillary serous
      carcinoma and peritoneal papillary serous carcinoma. Immunohistochemical staining
      results have indicated that these tumors are three separate primary malignancies.
      This case illustrates that ovarian serous borderline tumors (including
      micropapillary serous carcinoma) and peritoneal papillary serous carcinomas
      should be considered, like breast and ovarian carcinomas, tumors expressed in
      BRCA mutation carriers.

PMID- 11451558
TI  - Uterine artery aneurysm mimicking pelvic sarcoma. A case report and review of
      literature. raslanwf@aramco.com.sa.
AB  - We report a case of true uterine artery aneurysm in a 77-year-old diabetic woman,
      which was suspected radiologically as a pelvic sarcoma. The aneurysm was
      communicating with the atherosclerotic left uterine artery. Pelvic aneurysms
      carry the potential risk of massive intra-operative hemorrhage if the diagnosis
      was not established prior to operation.

PMID- 11451559
TI  - Sonolucency of a fresh hematoma in a case of marginal placental abruption.

PMID- 11451560
TI  - Persisting active and proliferative intrinsic ureteral endometriosis under GNRH
      agonists therapy: a case with immunohistological study.
AB  - We report the case of a 30-year-old patient who underwent a segmental ureteral
      resection with ureteroureterostomy because of the presence of a left
      ureterohydronephrosis caused by an intrinsic ureteral endometriotic lesion.
      Preoperatively, the patient received a 3 months course of GNRH agonists. The
      serum estradiol level was at 12 pg/ml at the moment of surgery. Histology and
      immunohistochemistry performed on the resected specimen showed the presence of
      numerous large haemorrhagic endometriotic foci containing very high levels of
      alpha-estrogen and progesterone nuclear receptors, a high Ki-67 labeling index
      and a strong positivity for EGF-receptor. This is the first report of
      immunohistochemical study performed on ureteral endometriosis preoperatively
      treated with GNRH agonists. Because hormonal treatments are often prescribed in
      the treatment of ureteral endometriosis, clinicians should be aware of the
      possibility of persisting very active and proliferative ureteral endometriotic
      lesions even under treatment with GNRH agonists and very low levels of
      circulating estradiol.

PMID- 11451561
TI  - HELLP syndrome in the 18th week of gestation in association with elevated
      angiotensin AT(1)-receptor autoantibodies.
AB  - We present a 24-year-old woman with a twin pregnancy who was with a typical HELLP
      syndrome at the 18th week of pregnancy. One fetus was dead, while the other was
      severely growth retarded. Our patient had agonistic autoantibodies directed at
      the angiotensin AT(1)-receptor. Termination of the pregnancy proved necessary.
      This report is the first to our knowledge associating HELLP syndrome with
      angiotensin AT(1)-receptor antibodies. Since the antibodies may have a pathogenic
      significance, their removal could permit the prolongation of pregnancy in
      preeclamptic and HELLP syndrome patients.

PMID- 11451562
TI  - Unilateral massive ovarian edema and polycystic ovaries. A case report.
AB  - Massive ovarian edema is a rare cause of ovarian enlargement in young women. We
      report a case in a 20-year-old woman with unilateral edema associated with the
      ultrasound appearance of polycystic ovary disease. Arterial and venous blood flow
      in the pedicle was observed with color and pulsed wave Doppler examination.
      Conservative management was successful.

PMID- 11451563
TI  - Observations of an idiopathic granulomatous mastitis.
AB  - Idiopathic granulomatous mastitis is a very rare benign breast disease, which
      mimics breast cancer both clinically and mammographically. Most cases have an
      unknown aetiology, however, we found an alpha-1-antitrypsin deficiency. A
      literature review is presented and the controversies in diagnosis and management
      are discussed.

PMID- 11451566
TI  - The transcriptional role of Smads and FAST (FoxH1) in TGFbeta and activin
      signalling.
AB  - The Smad family of proteins are critical components of the TGFbeta superfamily
      signalling pathway. Ligand addition induces phosphorylation of specific receptor
      regulated Smads, which then form heteromeric complexes with the common mediator
      Smad, Smad4. This complex then translocates from the cytoplasm into the nucleus.
      Once there, the R-Smad/Smad4 complex interacts with a variety of DNA binding
      proteins and is thereby targetted to a diverse array of gene promoters. The Smad
      containing DNA binding complex can then positively or negatively regulate gene
      expression through the recruitment of co-activators and co-repressors. Xenopus
      FAST (now known as FoxH1) was the first Smad DNA binding partner identified and
      the FoxH1 family now includes related proteins from mouse, human and Zebrafish.
      In all organisms examined, FoxH1 is expressed primarily during the earliest
      stages of development and thus FoxH1 is thought to play a critical role in
      mediating TGFbeta superfamily signals during these early developmental stages.
      Other Smad partners range from those that are ubiquitously expressed to others
      that are present only in specific cell types or developmental stages. Thus, it is
      the interaction of Smads with a wide range of specific transcriptional partners
      that is important for the generation of diverse biological responses to TGFbeta
      superfamily members.

PMID- 11451567
TI  - Transforming growth factor beta signalling in vitro and in vivo: activin ligand
      receptor interaction, Smad5 in vasculogenesis, and repression of target genes by
      the deltaEF1/ZEB-related SIP1 in the vertebrate embryo.
AB  - The identification and characterization of components of the transforming growth
      factor beta (TGFbeta) signalling pathway are proceeding at a very fast pace. To
      illustrate a number of our activities in this field, we first summarize our work
      aiming at the selection from a large collection of single residue substitution
      mutants of two activin A polypeptides in which D27 and K102, respectively, have
      been modified. This work has highlighted the importance of K102 and its positive
      charge for binding to activin type II receptors. Activin K102E, which did not
      bind to high-affinity receptor complexes, may be a valuable beta chain, when
      incorporated in recombinant inhibin to unambiguously detect novel inhibin binding
      sites at the cell surface. We then illustrate how Smad5 knockout mice and an
      overexpression approach with a truncated TGFbeta type II receptor in the mouse
      embryo can contribute to the identification of a novel TGFbeta-->TbetaRII/ALK1-
      >Smad5 pathway in endothelial cells in the embryo proper and the yolk sac
      vasculature. We conclude with a summary of our results with a Smad-interacting
      transcriptional repressor but focus on its biological significance in the
      vertebrate embryo.

PMID- 11451568
TI  - Intracellular and extracellular control of activin function by novel regulatory
      molecules.
AB  - Activin signal transduction is regulated through multiple mechanisms. We have
      identified novel regulatory proteins that control activin functions either
      intracellularly or extracellularly. As intracellular molecules, PSD-95/Dlg/ZO-1
      (PDZ) proteins that specifically associate with activin type II receptors
      (ActRIIs) were identified. We have named the molecules as activin receptor
      interacting proteins (ARIPs). ARIP1 has two WW domains and five PDZ domains,
      associates not only with ActRIIs but also with Smads, and controls activin
      functions intracellularly in neuronal cells. Another ARIP we have found has only
      one PDZ domain, and is likely to be involved in intracellular trafficking and
      sorting of activin receptor complexes in the cell. As an extracellular regulatory
      protein, we have identified a novel follistatin-like protein, named follistatin
      related gene (FLRG). Like follistatins, FLRG binds activins and bone
      morphogenetic proteins (BMPs) and controls their functions extracellularly. The
      mode of association of follistatin and FLRG with activins and their expression
      patterns are different, suggesting the distinct functions of follistatin and FLRG
      in vivo.

PMID- 11451569
TI  - Follistatin-related protein (FSRP): a new member of the follistatin gene family.
AB  - The identification and characterization of follistatin related protein (FSRP)
      suggests that the follistatin (FS) gene family may actually contain two sub
      families. The first includes FS and FSRP by virtue of their high degree of
      structural homology and comparable activin-binding activity, while the second sub
      family contains extracellular matrix proteins that possess one or more 10
      cysteine FS domains, but do not bind activin or related TGF-beta family members.
      Characterization of FSRP indicates that it binds activin with similar affinity
      and selectivity as FS, but does not bind heparin. Furthermore, although FSRP
      inhibits activin-mediated gene transcription in heterologous assays, FSRP is much
      less active than FS in the rat pituitary bioassay. When overexpressed in
      transgenic mice, FSRP may lead to interruption of follicular development and
      fertility in females but appears to have only a modest effect on males. These
      results suggest that FSRP is a structural, but not necessarily a functional
      homologue of FS.

PMID- 11451570
TI  - Studying TGF-beta superfamily signaling by knockouts and knockins.
AB  - The transforming growth factor beta (TGF-beta) superfamily has profound effects
      on many aspects of animal development. In the last decade, our laboratory and
      others have performed in vivo functional studies on multiple components of the
      TGF-beta superfamily signal transduction pathway, including upstream ligands,
      transmembrane receptors, receptor-associated proteins and downstream Smad
      proteins. We have taken gene knockout approaches to generate null alleles of the
      genes of interest, as well as a gene knockin approach to replace the mature
      region of one TGF-beta superfamily ligand with another. We found that activin
      betaB, expressed in the spatiotemporal pattern of activin betaA, can function as
      a hypomorphic allele of activin betaA and rescue the craniofacial defects and
      neonatal lethal phenotype of activin betaA-deficient mice. With the knockout
      approach, we have shown that the expression pattern of a component in the TGF
      beta superfamily signal transduction cascade does not necessarily predict its in
      vivo function. Two liver-specific activins, activin betaC and activin betaE are
      dispensable for liver development, regeneration and function, whereas
      ubiquitously expressed Smad5 has specific roles in the development of multiple
      embryonic and extraembryonic tissues.

PMID- 11451571
TI  - Antagonism of activin by inhibin and inhibin receptors: a functional role for
      betaglycan-glycan.
AB  - Activin and inhibin research has provided important insight into reproductive
      physiology as well as many areas involving regulation of cell growth,
      differentiation and function. Progress in understanding the roles of these
      hormones in various cell and tissue types has been complimented by novel
      discoveries at the molecular level that have shed light on ligand/receptor
      interactions, signaling mechanisms and regulation. While the receptors and
      signaling pathway for activin are now well characterized, the molecular basis for
      inhibin action has remained relatively unclear. Here we summarize recent advances
      in understanding inhibin's mode of action focusing on our recent identification
      of betaglycan-glycan as an inhibin co-receptor capable of mediating inhibin
      action.

PMID- 11451572
TI  - An emerging role for co-receptors in inhibin signal transduction.
AB  - While many transforming growth factor-beta (TGFbeta) superfamily ligands such as
      TGFbeta, activin, and the bone morphogenic proteins (BMPs) are critical to the
      control of growth, differentiation, and cell fate, inhibin has a more limited
      role and is primarily responsible for the regulation of one hormone from one cell
      type in the anterior pituitary. Inhibin is an endocrine hormone, produced by the
      gonads, that inhibits follicle stimulating hormone (FSH) release from the
      pituitary gonadotrope. The other hormones in the superfamily do not appear to act
      in an endocrine fashion, but rather control cell function in a paracrine or
      autocrine manner. Many components of the TGFbeta/activin/BMP signal transduction
      pathway have been elegantly defined; however, the mechanism of inhibin action has
      not been completely dissected. Several cell surface proteins that associate with
      inhibin have been identified recently, and these molecules may provide the clues
      necessary to understand how inhibin regulates reproductive function.

PMID- 11451573
TI  - Inhibin binding sites and proteins in pituitary, gonadal, adrenal and bone cells.
AB  - Activin signals via complexes of type I (50-55 kDa) and II (70-75 kDa) activin
      receptors, but the mechanism of inhibin action is unclear. Proposed models range
      from an anti-activin action at the type II activin receptor to independent
      actions involving putative inhibin receptors. Two membrane-embedded
      proteoglycans, betaglycan and p120, have recently been implicated in inhibin
      binding, but neither appears to be a signalling receptor. The present studies on
      primary cultures of rat pituitary and adrenal cells, and several murine and human
      cell lines were undertaken to characterise inhibin binding to its physiological
      targets. High affinity binding of inhibin to the primary cultures and several of
      the cell lines, like that previously described for ovine pituitary cells, was
      saturable and reversible. Scatchard analysis revealed two classes of binding
      sites (K(d) of 40-400 and 500-5000 pM, respectively). Affinity labelling
      identified [125I]inhibin binding proteins with apparent molecular weights of 41,
      74, 114 and >170 kDa in all cell types that displayed high affinity, high
      capacity binding of inhibin. Additional labelling of a 124 kDa species was
      evident in gonadal TM3 and TM4 cell lines. In several cases, activin (> or =20
      nM) competed poorly or not at all for binding to these proteins. The 74, 114 and
      >170 kDa inhibin binding proteins in TM3 and TM4 cells were immunoprecipitated by
      an anti-betaglycan antiserum. These three proteins correspond in size to the
      activin receptor type II and the core protein and glycosylated forms of
      betaglycan, respectively, that have been proposed to mediate anti-activin actions
      of inhibin, but the identity of the 74 kDa species is yet to be confirmed.
      Studies of [125I]inhibin binding kinetics and competition for affinity labelling
      of individual binding proteins in several cell lines suggest these three species
      and the 41 and 124 kDa proteins form a high affinity inhibin binding complex. In
      summary, common patterns of inhibin binding and affinity labelling were observed
      in inhibin target cells. Novel inhibin binding proteins of around 41 and 124 kDa
      were implicated in the high affinity binding of inhibin to cells from several
      sources.

PMID- 11451574
TI  - Enzyme immunoassays for inhibins, activins and follistatins.
AB  - In this short review, the authors summarise the inhibin, activin and follistatin
      assays developed by the Oxford group and collaborators, and some of the main
      purposes for which they have been applied. Over 500 research publications have
      used these assays. We also discuss new assays recently developed at the request
      of our collaborators for particular applications, and comment on outstanding
      assay problems.

PMID- 11451575
TI  - Development of an inhibin alpha subunit ELISA with broad specificity.
AB  - Inhibin immunoassays with a sufficiently broad specificity to detect all alpha
      subunit-containing forms are of value in detecting and monitoring various ovarian
      cancers. Assays to date with this specificity are not readily amenable to wide
      diagnostic application. The objective of this study was to develop a sensitive
      two-site ELISA using alpha subunit-directed monoclonal antibodies (Mabs) able to
      detect all forms of inhibin to replace a previously described alpha subunit
      directed immunofluorometric assay (IFMA). In this study, the major inhibin
      epitopes in the two polyclonal antisera used in the alphaC IFMA were initially
      identified and Mabs were raised to these regions. These Mabs in conjunction with
      the inhibin alpha subunit R1 Mab (Groome) were used to develop alpha subunit
      ELISAs with high sensitivity. Application of these assays to human serum and
      human follicular fluid following fractionation by an immunoaffinity/preparative
      PAGE/electroelution procedure which separated inhibins according to their
      molecular weights, indicated that the specificity of the various ELISAs differed
      between Mab combinations with preferences noted for either the alpha subunit or
      dimeric forms. A combination of Mabs in an ELISA was identified which provided
      data which matched that obtained with the alphaC IFMA and which may be useful as
      a replacement inhibin assay in clinical studies.

PMID- 11451576
TI  - Inhibins, activins and follistatin: actions on the testis.
AB  - While the early studies of the inhibins, activins and follistatins concentrated
      on their role as endocrine regulators of FSH secretion, recent data has
      emphasized the local actions of the activins and follistatin. Inhibin, through
      its capacity to suppress FSH secretion can modulate numerous processes within the
      testis. However, to date, evidence to support a local role for inhibin is
      limited. In contrast, activin and its binding protein follistatin are produced by
      a large number of cell-types within the testis raising the possibility of a range
      of paracrine and autocrine actions. These include the modulation of androgen
      production, influence on the proliferation of Sertoli cells and germ cells as
      well as the capacity to influence the structural and functional features of
      mitochondria within germ cells. Some of these actions are carefully controlled in
      a temporal relationship during the development of testicular function in the rat
      in which there is no separation in time between birth and the onset of
      spermatogenesis. Given the range of actions of activin in different cell-types,
      recognition of systems that are designed to modulate its actions are crucial in
      enhancing our understanding of how these many roles can be compartmentalized.

PMID- 11451577
TI  - Operation of the follicle-stimulating hormone (FSH)-inhibin B feedback loop in
      the control of primate spermatogenesis.
AB  - This paper reviews our current understanding of the function and operation of the
      follicle-stimulating hormone (FSH)-inhibin feedback loop in the male rhesus
      monkey (Macaca mulatta). Inhibin B is the major testicular inhibin in the monkey,
      and the pattern of secretion of this hormone during postnatal development is
      temporally coupled to that of gonadotropin. Inhibin B secretion by the Sertoli
      cell is stimulated by FSH and inhibited by luteinizing hormone (LH), the latter
      presumably acting via Leydig cell production of testosterone (T). The dynamics of
      the FSH-inhibin B feedback loop in the adult monkey is revealed following
      unilateral orchidectomy (UO). Interestingly, a sustained, 50% deficit in inhibin
      B secretion occurs after UO and this persistent error signal, in turn, results in
      elevated concentrations of FSH in the circulation. The elevated secretion of FSH
      appears to be the principal drive for the increased sperm output by the remaining
      testis. Available data for the functioning of the FSH-inhibin B feedback loop in
      the human male are placed in perspective, and a model for the negative feedback
      regulation of sperm number in primates is proposed.

PMID- 11451578
TI  - Serum inhibin B levels during male childhood and puberty.
AB  - Inhibin B is a testicular peptide hormone that regulates FSH secretion in a
      negative feedback loop. In males serum levels of inhibin B are detectable
      throughout life with prominent changes in the first year of life and during
      puberty. Serum inhibin B is normally detectable throughout childhood where it is
      a direct marker of the presence and function of Sertoli cells. The inhibin B
      analysis has proven useful in the diagnosis of patients with non-palpable testes.
      Undetectable or low inhibin B levels are observed in boys with either congenital
      or acquired absence of testicular tissue whereas normal or near-normal levels are
      seen in cryptorchidism and disorders with preserved Sertoli cell function in
      spite of absence of germ cells or impaired androgen biosynthesis or action.
      During puberty a developmental change in the regulation of serum inhibin B
      occurs. In contrast to childhood inhibin B levels, inhibin B production in adult
      men is dependent on the presence of certain germ cells in the seminiferous
      tubules, most likely involving the pachytene spermatocytes and early spermatids.
      Thus, in adult men serum inhibin B levels are closely related to spermatogenesis
      with undetectable or low levels observed in SCO syndrome and early stage
      spermatogenic arrest whereas normal or near normal levels are observed in men
      with late stage spermatogenic arrest or obstructive forms of azoospermia. These
      clinical findings are in accordance with immuno-histological studies of the
      expression of inhibin B subunits in human testis.

PMID- 11451579
TI  - Clinical studies: inhibin in the adult male.
AB  - The current generation of inhibin assays have allowed the demonstration that
      inhibin B is the long-postulated testicular factor comprising the feedback
      inhibitory pathway between the testis and FSH secretion. The inverse relationship
      between inhibin B and FSH secretion is seen in both normal men and in testicular
      pathologies. Although inhibin B concentrations are increased by gonadotrophin
      administration, adult secretion is only partly gonadotrophin dependent and
      appears more closely related to the presence of germ cells. Thus, inhibin B
      concentrations are maintained at least at 30% of normal following gonadotrophin
      suppression, but fall to undetectable levels following loss of all germ cells,
      e.g. by testicular irradiation. The direct positive correlation between inhibin B
      and sperm concentration in normal men indicates that inhibin B quantitatively
      reflects the number of spermatozoa being released. Data from studies of infertile
      men undergoing testicular biopsy is providing information as to the particular
      stages of spermatogenesis involved. These intercellular relationships may
      underlie the relative resistance of inhibin B to suppression by some hormonal
      contraceptive regimens, despite azoospermia being induced. Inhibin B is also
      present in seminal plasma. There is a far wider range of concentration in seminal
      plasma than in blood and the significant relationship with sperm concentration
      indicates that inhibin secretion into the ejaculate is a marker of the functional
      activity of the seminiferous tubule. This relationship with sperm production may
      be a useful marker in some contexts, as changes are more dynamic than in the
      circulating hormone.

PMID- 11451580
TI  - Measurement of inhibin A and activin A in pregnancy--possible diagnostic
      applications.
AB  - Knowledge of the roles of inhibins and activins has progressed rapidly since the
      development of a specific and sensitive assay that can be used for measurements
      on human serum and amniotic fluid samples. There is a sound theoretical basis for
      the role of transforming growth factor-beta family members in inflammatory
      processes, many of which are analogous to implantation, parturition and a variety
      of pathological conditions in pregnancy. This review explores the potential use
      of assays for inhibins and activins in clinical practice and suggests further
      areas for research.

PMID- 11451581
TI  - Changes in inhibins and activin secretion in healthy and pathological
      pregnancies.
AB  - Inhibin-related proteins are involved in the control of the feto-maternal
      communication required to maintain pregnancy. Human placenta, decidua, and fetal
      membranes are the major sites of production and secretion of activin A, inhibin A
      and inhibin B in maternal serum, amniotic fluid, and cord blood. The availability
      of suitable assays developed in the last years has enabled the measurement of
      inhibins and activin A in their dimeric forms, in order to investigate their role
      in physiological conditions of pregnancy. The studies conducted on inhibin
      related proteins and human pregnancy suggested the possibility of an involvement
      of inhibin A and activin A in the pathogenesis of gestational diseases. In fact,
      several lines of evidence underline the potential role and the clinical
      usefulness of inhibin-related proteins measurement in the diagnosis, prevention,
      prognosis and follow-up of different gestational pathologies such as early
      pregnancy viability, Down's syndrome, fetal demise, pre-eclampsia, pregnancy
      induced hypertension, preterm delivery and intrauterine growth restriction. The
      measurement of inhibin A and activin A into the biological fluids of pregnancy
      will offer in the future, further possibilities in the early diagnosis,
      prediction, and monitoring diseases of pregnancy.

PMID- 11451582
TI  - Physiological and regulatory roles of activin A in late pregnancy.
AB  - Unexplained fetal death in utero in late pregnancy represents an increasing
      proportion of perinatal deaths. It has been assumed that critical hypoxia is the
      likely mechanism underlying these losses, but the lack of a physiological marker
      has hampered both confirmation and prediction which could lead to timely
      intervention. In this paper, we report studies on hypoxia that we have performed
      in chronically cannulated late pregnant sheep, complemented by parallel
      investigations undertaken in human pregnancies. Our initial studies were directed
      towards determining activin secretion in the fetus and mother during late
      gestation, and immediately after fetal surgery using a sheep model. This led us
      to propose that there may be a relationship between hypoxia and activin A,
      follistatin and prostaglandin (PG) release from the feto-placental unit.
      Subsequent studies have been directed towards examining this potential
      relationship in sheep and in humans with compromised pregnancies. As a result of
      these studies, we have identified a potential mechanism by which activin A may be
      involved in regulating the response of the fetus to hypoxic insult. Activin A and
      follistatin concentrations increased in late gestation in ovine maternal plasma
      and in fetal fluids. Feto-placental hypoxemia or maternal isocapnic hypoxemia,
      leading to fetal hypoxia, were specific triggers for an acute increase in fetal
      activin A and follistatin concentrations during late gestation. The source and
      secretion of activin A, follistatin, and the associated release of PGE(2,) from
      within the feto-placental unit varied according to the site of the insult. The
      concomitant secretion of activin A and PGE(2) into the fetal circulation and
      amniotic fluid during reduced uterine blood flow provides an insight into the
      physiological regulatory mechanisms that might be involved. Changes observed in
      maternal activin A concentrations in mid and late gestation in the human may also
      be associated with fetal compromise. In human pregnancies, elevated activin A
      concentrations were observed in maternal plasma in mid and late gestation, in
      association with severe pre-eclampsia and with severe fetal growth restriction,
      compared to those observed in pregnancies with constitutionally small, healthy
      fetuses. Activin A was also elevated in maternal and arterial cord plasma in
      women at term during labour and immediately prior to undergoing emergency
      Caesarean section for failure to progress. These findings offer exciting new
      possibilities to gain insights into the mechanisms that underlie the maintenance
      of fetal wellbeing and provide a rationale for the potential that activin A may
      prove to be a useful clinical marker of fetal distress.

PMID- 11451583
TI  - Production and actions of inhibin and activin during folliculogenesis in the rat.
AB  - Evidence to enhance the premise that inhibin and activin are local regulators of
      ovarian folliculogenesis is presented in this review. Granulosa cells (GC) have
      been identified as the source of inhibin/activin in the ovary on the basis of
      mRNA and protein localisation and the measurement of the inhibin forms in GC
      conditioned media. Expression of the subunit mRNAs changed with follicular
      development, being maximal in the ovaries of 8-day-old rats, where secondary
      follicles predominate. The expression of beta subunit mRNAs by GC isolated from
      diethylstilboestrol (DES)-treated immature rats, was reduced in the absence of
      any change in alpha subunit mRNA expression. Dimeric inhibin-A, -B and free alpha
      subunit were produced by ovarian cell cultures prepared from 4- to 12-day-old
      rats. Inhibin-A production by these cultures was responsive to FSH and TGF-beta,
      with preantral follicles of day 8 ovaries exerting effects so profound that the
      inhibin A/alpha subunit ratio increased, most likely due to a stimulation of
      beta(A) subunit production. In contrast, inhibin-B was not stimulated by TGF-beta
      until day 8 and FSH until day 12. Fractionation of GC conditioned media revealed
      a prominence of free alpha subunit and inhibin-A, but little inhibin-B,
      suggesting that inhibin-B production declines with follicular development.
      Activin receptor types I and II, Smads 1-8 and betaglycan (beta-glycan) mRNAs
      were present in the rat ovary and showed distinct patterns of expression between
      postnatal days 4 and 12. Oocytes and GC localised activin receptor, Smad and beta
      glycan proteins, with beta-glycan also present in theca cells (TC). These data
      indicate that activin/TGF-beta signalling machinery and factors which influence
      these pathways, are present in the postnatal rat ovary. Our hypothesis that
      inhibin and activin play important and changing autocrine/paracrine roles in the
      growth and differentiation of follicles, including the oocyte, has been supported
      by these studies.

PMID- 11451584
TI  - The inhibins and ovarian cancer.
AB  - Interest in inhibin as a marker of ovarian malignancy was stimulated by the
      description of elevated immunoreactive inhibin levels in the sera of patients
      with granulosa cell tumours. Several groups have confirmed the value of serum
      inhibin in the diagnosis and follow-up of patients with this uncommon malignancy.
      Immunoreactive inhibin levels are also frequently elevated in patients with
      mucinous cystadenocarcinoma and less frequently in other forms of ovarian tumour.
      Assay of sera using the specific dimeric inhibin assays has shown that ovarian
      tumours are able to secrete dimeric inhibin particularly inhibin B. The less
      specific alpha-subunit directed assays, however, most frequently show elevated
      concentrations. Used in combination with CA125 as a dual tumour marker, it
      appears in principle that inhibin can be a useful diagnostic agent.
      Immunohistochemistry for the inhibin subunits has been reported with increasing
      frequency as a helpful method to assess suspected ovarian stromal cell tumours.
      Its diagnostic accuracy for other types of ovarian adenocarcinoma appears less
      reliable. Expression of the inhibin subunit mRNAs has been demonstrated in a
      variety of ovarian malignancies. The observation that inhibin levels are elevated
      in ovarian cancer has stimulated studies of their relevance to the molecular
      pathogenesis of these malignancies. Findings to date have been largely negative
      with no evidence for activating mutations of the FSH receptor or of the post
      receptor signalling pathway proteins.

PMID- 11451585
TI  - The contribution of inhibins and activins to malignant prostate disease.
AB  - The normal human prostate expresses inhibin and activin subunits. In prostate
      cancer, the inhibin alpha subunit gene is down regulated and this is associated
      with loss of heterozygosity (LOH) at the gene locus and methylation of the
      promoter. These data support the hypothesis that the inhibin alpha subunit is
      tumor suppressive in the prostate. The pluripotent effects of activins and the
      similarities to transforming growth factor beta (TFGbeta) suggest a role for
      activins in progression to malignancy, whereby, the normal growth inhibitory
      action of activin A observed on benign cells is lost with the acquisition of
      activin resistance in prostate cancer cells. The mechanisms of rendering tumor
      cells resistant to activin A may include: alteration in activin binding protein
      (follistatin) synthesis and/or dimerisation with activin beta(C) to form novel
      activin dimers. The contribution of the activin signalling cascade to malignancy
      requires further evaluation to identify the synergies and differences to other
      members of the TGFbeta superfamily.

PMID- 11451586
TI  - Evidence for activin A and follistatin involvement in the systemic inflammatory
      response.
AB  - The inflammatory cascade is a multifactorial process regulated by interwoven
      cytokine and growth factor networks. This review summarizes the emerging evidence
      that implicate activin A and follistatin in inflammatory processes. Our recent
      studies have determined that activin A is released early in the cascade of
      circulatory cytokines during systemic inflammatory episodes, roughly coincident
      with tumour necrosis factor (TNF)-alpha and before interleukin (IL)-6 and
      follistatin. The source(s) of this activin A are not yet established, but prime
      candidates are monocytes/macrophages, other immune cell types or vascular
      endothelial cells. Clinical data are limited, but activin beta(A) subunit mRNA or
      activin A protein is elevated in inflammatory bowel diseases and inflammatory
      arthropathies, and circulating concentrations of follistatin are elevated in
      patients with sepsis. In more mechanistic approaches, in vitro studies show that
      activin A can have both pro- and anti-inflammatory actions on key inflammatory
      mediators such as TNFalpha, IL-1beta and IL-6. Furthermore, there is emerging
      understanding of how the intracellular signaling pathway for activin A,
      incorporating Smads, may interact with and be modulated by other key regulatory
      cytokines and growth factors.

PMID- 11451587
TI  - Expression of activin A in inflammatory arthropathies.
AB  - The findings that bone marrow fibroblastoid stromal cells are important for
      activin A production prompted our investigation of activin A expression in
      fibroblast-like synoviocytes in joint capsule in this and previous studies. In
      the proliferative reactive synovial membrane obtained from rheumatoid arthritis
      patients, activin A is detected prominently in the fibroblastoid synovial cells,
      as well as in the smooth muscle and the endothelial layer of the arteries in
      these vascularized proliferative tissues. The concentration of activin A in the
      rheumatoid arthritis synovial fluid was 33.6+/-5.0 ng/ml, much higher than the
      activin A content of osteoarthritis fluid (10.0+/-1.1 ng/ml). Furthermore, our
      previous studies also showed that inflammatory cytokines, such as interleukin
      (IL)-1, transforming growth factor (TGF)-beta, interferon (IFN)-gamma, IL-8, and
      IL-10 markedly enhance the expression of activin A mRNA in synoviocytes. These
      findings are consistent with our studies in regard to the regulatory control of
      activin A production in bone marrow stroma and monocytes. In addition, the
      relationship of activin A to IL-6-induced biological activities in various cell
      types was also investigated. Although activin A has not been directly associated
      with inflammatory processes, future studies are needed to investigate its
      production in response to the accumulated levels of inflammatory cytokines in the
      synovium of the patients, as well as the quantitative differences in activin A
      concentrations in many patients with other inflammatory diseases.

PMID- 11451588
TI  - The roles of activins in repair processes of the skin and the brain.
AB  - A recent study from our laboratory demonstrated a strong upregulation of activin
      expression during cutaneous wound healing. To further analyze the role of activin
      A in skin morphogenesis and wound repair, we generated transgenic mice that
      overexpress activin A under the control of the keratin 14 promoter. The latter
      targets expression of transgenes to the basal, proliferating layer of the
      epidermis. Hetero- as well as homozygous transgenic animals were viable and
      fertile. However, they were smaller than non-transgenic littermates and they had
      smaller ears and shorter tails. Histological analysis of their skin revealed
      dermal hyperthickening, mainly due to the replacement of fatty tissue by
      connective tissue, and an increase in suprabasal, partially differentiated
      epidermal layers. After cutaneous injury, a strong enhancement of granulation
      tissue formation was observed. Furthermore, the extent of re-epithelialization
      was increased in some of the wounds. These data demonstrate that activin A is a
      potent stimulator of the wound healing process. Using an in vivo model of local
      brain injury, we found that activin A also plays a significant role in the early
      cellular response to neuronal damage. Expression of activin mRNA and protein is
      markedly upregulated within a few hours of injury. If applied exogenously,
      recombinant activin A is capable of rescuing neurons from acute cell death.
      Studying the interaction between bFGF, a well-established neuroprotective agent,
      which is currently being tested in stroke patients, and activin A, we arrived at
      the unexpected conclusion that it is the strong induction of activin A by bFGF
      which endows the latter with its beneficial actions in patients. These findings
      suggest that the development of substances directly targeting activin expression
      or receptor binding should offer new possibilities in the acute treatment of
      stroke and brain trauma.

PMID- 11451589
TI  - Role of the activin-follistatin system in the morphogenesis and regeneration of
      the renal tubules.
AB  - Activin A inhibits branching tubulogenesis of the kidney during development.
      Activin A also inhibits branching tubulogenesis in MDCK cells, an in vitro
      tubulogenesis model. On the other hand, follistatin, an antagonist of activin A,
      reverses the effect of activin A and induces branching tubulogenesis. Follistatin
      also promotes tubular regeneration after ischemia/reperfusion injury. The
      activin/follistatin system is one of the important regulatory systems modulating
      developmental and regeneration processes of the kidney.

PMID- 11451590
TI  - Involvement of activin in the regulation of bone metabolism.
AB  - Osteogenic activities of activin, a member of TGF-beta superfamily, have been
      shown in both in vivo and in vitro studies. Local injection of activin promoted
      fracture healing in rat fibula fracture models. Since both activin and its
      receptor are expressed during fracture healing, activin would be involved in the
      healing process via autocrine and/or paracrine mode of action. Activin was
      abundantly stored also in normal bone matrix, presumably produced by osteoblasts
      in the process of normal bone formation. It was observed that activin was
      released in the culture of neonatal mouse calvaria, and the release was strongly
      coupled with bone resorption. Thus, activin could be involved in the regulation
      of bone remodeling as one of coupling factors, as was suggested for TGF-ss.
      Systemic administration of activin in aged ovariectomized rats, in which bone
      mass decreases due to uncoupling between bone resorption and formation, increased
      both bone mass and mechanical strength of vertebral bodies. These findings
      suggest physiological roles of activin in the regulation of bone formation, and
      further, its possible usefulness for the therapy of fracture and osteoporosis.

PMID- 11451592
TI  - Initial experience with a composite autologous skin substitute.
AB  - Patients with large burns are surviving in increasing numbers, but there remains
      no durable and reliable permanent skin replacement. After initial favorable small
      animal experiments, a pilot trial of a composite skin replacement was performed
      in patients with massive burns. A composite skin replacement (CSR) was developed
      by culturing autologous keratinocytes on acellular allogenic dermis. This
      material was engrafted in patients with massive burns and compared to a matched
      wound covered with split thickness autograft. With human studies committee
      approval, 12 wounds in 7 patients were grafted with CSR while a matched control
      wound was covered with split thickness autograft. These 7 children had an average
      age of 6.4+/-1.4 yr and burn size of 75.9+/-5.0% of the body surface. Nine wounds
      were acute burns and three were reconstructive releases. Successful
      vascularization at 14 days averaged 45.7+/-14.2% (range 0-100%) in the study
      wounds and 98+/-1% (range 90-100%) in the control sites (P<0.05). Reduced CSR
      take seemed to correlate with wound colonization. All children survived. While
      CSR did not engraft with the reliability of standard autograft, this pilot
      experience is encouraging in that successful wound closure with this material is
      possible, if not yet dependable. It is hoped that a more mature epidermal layer
      may facilitate engraftment, and trials to explore this possibility are in
      progress.

PMID- 11451593
TI  - How long can cryopreserved skin be stored to maintain adequate graft performance?
AB  - Skin graft preservation for the purpose of delayed application is still a basic
      tool in burn treatment and plastic and reconstructive surgery. As the demand for
      skin allografts has increased the responsibility for processing, storage and
      evaluation of graft performance of preserved skin has become an important issue
      of banking organizations. The present experiments were undertaken to determine
      how long can cryopreserved cadaveric skin be stored to maintain adequate graft
      performance? We applied a mouse recipient model, developed by us: Human cadaveric
      skin cryopreserved and stored for 5,6 or 7 years was grafted on Balb/c mice, and
      primary take was evaluated by gross observation and predetermined histologic
      criteria after 7 days. The results demonstrate that graft performance of
      cryopreserved skin decreased with time, as reflected in the lower percent of
      samples with high score of separate histologic criteria after prolonged storage.
      Nevertheless, paired comparison analysis between cryopreserved and fresh skin
      indicated that this decrease was not significant for storage of 5 years; whereas
      it was highly significant for 6 years of storage. Linear regression analysis
      indicated that there was no correlation between the score of the histologic
      criteria and storage period for upto 65 months. These results are in line with
      the paired comparison analysis. We feel that our in vivo model and analysis may
      be used as an evaluation procedure for transplantation performance of banked
      skin.

PMID- 11451594
TI  - Dermal cellular inflammation in burns. an insight into the function of dermal
      microvascular anatomy.
AB  - The damage caused by thermal trauma is augmented by the subsequent inflammatory
      response in a similar fashion to reperfusion injury. Animal studies have
      demonstrated a significant role for neutrophils in this delayed damage, but
      little is known about the numbers of neutrophils or other leucocytes that enter
      human skin following burns. We have longitudinally examined profiles of leucocyte
      migration into five cases of human partial thickness burns in relation to
      continued dermal microvascular destruction during the acute post-burn period. All
      burn wounds had a rapid influx of neutrophils that was followed by a delayed
      influx of macrophages. Compared to the controls, the two superficial burns also
      had rapid and sustained influx of CD4 and CD8 lymphocytes via patent post
      capillary venules in the dermal superficial vascular plexus, whilst in the three
      deeper burns, in which this superficial vascular plexus was occluded, the number
      of lymphocytes decreased. These results suggest that the patterns of leucocyte
      extravasation were dependent on the initial level of vascular occlusion,
      indicating that the dermal microvascular anatomy plays a pivotal role in
      determining the composition of the extravascular inflammatory cell infiltrates.
      The potential importance of this finding is highlighted by the differences in
      wound behaviour associated with the different leucocyte profiles.

PMID- 11451595
TI  - Selective decontamination of the digestive tract in severely burned pediatric
      patients.
AB  - Infection is still one of the leading causes of morbidity and mortality in
      severely burned patients. Evidence suggests that many of the responsible
      organisms are endogenous. Systemic antibiotic prophylaxis is not effective, and
      produces resistant strains of microorganisms. SDD has been postulated to be
      beneficial for controlling and decreasing infections in critically ill patients.
      Its efficacy in severely burned patients, however, remains controversial. In
      order to analyze the efficacy of selective decontamination of the digestive (SDD)
      tract, to decrease the bacterial colonization of the aerodigestive tract and burn
      wounds, and the incidence of septic complications in severely burned children, 23
      pediatric patients affected of severe burns were prospectively randomized in a
      double-blinded study. Eleven patients received SDD (Polymyxin E, Tobramycin, and
      Amphotericin B), and 12 placebo. Demographics, hospital course, microbiology
      results, complications, infectious episodes, and serum levels of IL-1beta, IL-6,
      IL-10, and TNF-alpha were compared to determine the efficacy of SDD. Colonization
      rates to the wound, sputum, nasogastric aspirates, and feces were similar.
      Pneumonia, sepsis and other complications had similar incidence in both groups.
      Serum levels of all cytokines studied were also comparable, suggesting a similar
      inflammatory status in all patients, regardless of the treatment received.
      Patients in the SDD group, however, had a significantly higher incidence of
      diarrhea (P=0.003). We can conclude that selective decontamination of the
      digestive tract with Polymixin E, Tobramycin and Amphotericin B is not effective
      to decrease bacterial colonization and infectious episodes in severely burned
      pediatric patients.

PMID- 11451596
TI  - The effect of short-term growth hormone treatment on growth and energy
      expenditure in burned children.
AB  - Delays in growth are commonly observed in children who have sustained a severe
      cutaneous burn. The reasons for this growth delay are not completely known, but
      in adults, plasma growth hormone (GH) levels have been shown to decrease after
      thermal injury. If this is also the case in severely burned children, the low GH
      levels may contribute to their chronic growth delay. We propose that treatment
      with rhGH may prevent this burn-induced growth delay. Height velocities were
      measured for up to 2 years after injury in 38 burned children (age 7+/-1 years)
      with a 64+/-2% total burn surface area (TBSA) burn and a 59+/-3% third-degree
      burn who received 0.2 mg/kg/day rhGH during hospitalization. These height
      velocities were compared to 41 burned children (age 8+/-1 years) with a 64+/-3%
      TBSA burn and a 60+/-3% TBSA third-degree burn who were treated similarly but did
      not receive rhGH. Height velocities and height percentiles were compared to
      standard height velocity and percentile nomograms of unburned children. To
      determine the effect of rhGH on energy requirements, resting energy expenditures
      (REE) were measured by indirect calorimetry and compared to values calculated
      from the Harris-Benedict equation. All data are presented as mean+/-S.E.M. No
      differences in average height percentile could be shown between those receiving
      GH and controls at admission and 6 months after burn. There was, however, a
      significant difference (P<0.05) in height velocity during the first 2 years after
      burn between GH (47th+/-6 percentile) and controls (32nd+/-5 percentile). For
      rhGH-treated children, the REE was elevated by 34+/-4% versus 35+/-5% for
      controls. Recombinant human GH, given during acute hospitalization, maintained
      growth in severely burned children who would otherwise experience a significant
      growth delay. Treatment with rhGH did not atttenuate their elevated REE.

PMID- 11451597
TI  - Metabolic disorder in myocardiac intracellular free calcium after thermal injury.
AB  - Cutaneous burn trauma causes functional inhibition of the heart, but the
      mechanism is unclear. Using a high dissociation constant (K(D)) calcium indicator
      TF-BAPTA and 19F MR spectroscopy, the relationship between the changes of
      cytosolic free calcium and cardiac function after burn trauma was examined.
      Sprague-Dawley rats received scald (43% TBSA) or sham burns. Twenty-four hours
      later, the hearts were excised and perfused by the Langendorff method with a
      modified phosphate-free Krebs-Henseleit bicarbonate buffer. Left ventricular
      developed pressure (LVDP) was recorded through a catheter attached to an
      intraventricular balloon. At the same time, 31P and 19F nuclear magnetic
      resonance (NMR) spectroscopy was perforined before and after TF-BAPTA loading.
      LVDP of the heart from burned rats was 40% less than in sham burn rats (65+/-6 vs
      110+/-12 mmHg, P<0.01). Cytosolic free calcium increased about four-fold in those
      hearts from the burn group compared to the sham burn group (0.807+/-0.192 vs
      3.891+/-0.929 microM). Loading TF-BAPTA in those hearts only caused about a 15
      20% decrease in LVDP. PCr/Pi ratio also decreased significantly with this
      loading, but ATP signals were not affected. In conclusion, the inhibition of
      cardiac contractility caused by burn trauma correlated with the overload of
      cytosolic free calcium in the heart.

PMID- 11451598
TI  - Phosphate buffer in alkali eye burns as an inducer of experimental corneal
      calcification.
AB  - Corneal calcification is a common problem in severe inflammation, chronic
      glaucoma, renal disorders and other diseases with disturbed calcium and
      phosphorus metabolism. The pathogenesis of corneal calcifications in ocular
      diseases is not yet completely understood. We present a model of an induced
      corneal calcification by local treatment. In a double-masked experiment 16
      rabbits underwent eye burn of one cornea followed by immediate rinsing (160 ml)
      with isotonic phosphate buffer (n=8) or saline solution (n=8) three time a day
      for 16 days. Tissues were excised, shock frozen and cut into 10 microm slices,
      freeze dried and coated with evaporated carbon. In the phosphate buffer group an
      early onset of corneal opacification occurred resulting in completely white
      corneas after 16 days, combined with corneoscleral ulceration. The other group
      showed similar corneal erosion and a little corneal ulceration, but no
      opacifications. The opacifications of the phosphate buffer group could be
      identified as calcifications by direct measurements of calcium and phosphate (by
      energy dispersive X-ray analysis on corneal samples). In conclusion,
      inappropriate application of phosphate leads to uncontrolled calcifications of
      the cornea after severe burns to the eye. This reflects clinically observed
      calcifications after eye burns and possibly the adverse side effects of phosphate
      buffered eye drops being applied in ophthalmology.

PMID- 11451599
TI  - Topical use of Sucralfate Cream in second and third degree burns.
AB  - This clinical study was undertaken to test the efficacy of topical Sucralfate
      Cream in second and third degree burns. Topical Sucralfate Cream has been used on
      a wide variety of lesions from radiation proctitis and dermatitis to
      keratoconjunctivitis with remarkable results. The study was carried out in two
      phases. The first phase comprised 60 patients, 30 of whom were treated with
      Sucralfate Cream while the other 30 were treated with other topical antimicrobial
      agents. Twenty-one of the patients in the study group had second-degree burns and
      nine patients' third degree burns. In the second phase, a double blind study was
      carried out on 25 patients where one area of burns was treated with Sucralfate
      Cream while another control area of the same patient was treated with a placebo
      ointment, containing the excipients used during preparation of the Sucralfate
      Cream, without Sucralfate. In the first phase, it was seen that the period of
      epithelialisation of second degree burns in the study group treated with
      Sucralfate Cream was 18.8 days compared with 24.6 days with other topical agents.
      This difference is statistically significant with a P value of <0.00001. In the
      double blind study, also healing in the areas treated with Sucralfate was more
      rapid than those treated with bland placebo ointment. The difference in the two
      rates of healing was statistically significant with a P value of 0.00067.
      Histopathological studies were also carried out in 10 patients of phase I of the
      trial. Sucralfate Cream promotes rapid epithelialisation of second degree burns
      with minimal said effects and offers another topical agent in the burn care
      specialist's armamentarium.

PMID- 11451600
TI  - Assault by burning--a reappraisal.
AB  - Assault by burning is a serious form of trauma that often results in higher
      incidence of inhalation injury, longer intensive care unit (ICU) and hospital
      stay, and higher mortality rate than is observed in the general burn population.
      We evaluated the epidemiology and outcome of assault burn victims treated in a
      tertiary burn center over a 6-year period. Among the 1063 acute burn patients who
      had been admitted to the Burns Unit between March 1993 and February 1999, 28
      (2.6%) had assault burn injuries either by scald, chemical or fire. The mean
      extent of burn was 21.9%+/-20.8% (range 2-90%) total body surface area and the
      mean length of hospital stay was 65.2+/-107.3 days (range 1-565). Nineteen out of
      25 patients (67.9%) underwent 76 operations. Nine patients had inhalation
      injuries requiring intubation and ICU admission. Three patients died in the
      series, which yielded a mortality rate of 10.7%. Compared to the general burn
      population, the assault burn group had significantly larger burn size (P<0.001),
      higher incidence of inhalation injury (P<0.001), longer ICU and hospital stay
      (P<0.001), and higher mortality rate (P<0.005). When these 28 victims were
      grouped according to the type of assault burn injury into a fire group, chemical
      group and scald group, all the 9 ICU admission and the 3 mortalities belonged to
      the fire group. Assault by fire resulted in larger burn size (P=0.03), more
      inhalation injury (P<0.001) and longer ICU stay (P=0.02). Although the fire group
      had a longer hospital stay and higher mortality rate, this was statistically
      insignificant.

PMID- 11451601
TI  - Epidemiology and man-days loss in burn injuries amongst workers in an oil
      industry.
AB  - This retrospective study, conducted at the Indian Oil Corporation Ltd. (Assam Oil
      Division) Hospital, Digboi, in a period of 5 yr amongst workers of IOC Ltd. (AOD)
      describes work-associated injuries. Out of 2320 cases of different types of
      injuries involving workers over this period, 820 (35.3%) occurred at the
      workplace. 1430 (61.6%) at home or other places and 70 (3.1%) occurred on way to
      the workplace. Burn injuries were found in 132 cases (5.8% of the total
      injuries), but constituted 12.6% of the accidents at the workplace. The majority
      of the other injuries were soft tissue injuries, including sprains 1288 (55.5%)
      and hand injuries 688 (29.5%). Major burns (above 20% BSB) were found only in 5
      cases. The most common sites of involvement in minor burns were the hands (45
      cases), the legs (35 cases) and face (20 cases) with the remaining involving the
      chest and abdomen. Scald injury was observed in 66/132 (50%) cases, contact burns
      in 13/132 (10%) cases, flame burns in 33/132 (25%) cases, chemical burns in
      11/132 (8.3%), and electrical burns in 9/132 (7%) cases. Mortality was 1.5%.
      Working days lost (man-days loss) in burn injuries was found to be higher in
      comparison to other injuries of similar severity. Causation of industrial burns
      is discussed and importance of prevention of burns in industries has been
      emphasised.

PMID- 11451602
TI  - Serial tissue expansion for reconstruction of burns of the head and neck.
AB  - There is little reported on serial tissue expansion for reconstruction of burns
      of the head and neck. Fourteen children (mean age 7.8 years, range 3-11 years)
      treated over almost an 11 year period, had a total of 67 expanders used. Fourteen
      children had expansion performed on the first occasion, 14 again on a second
      occasion, 10 on a third occasion and one on a fourth occasion. The major
      complication rate (expander extruded prior to completion of the expansion
      process) was 21,25 and 14%, respectively. In all cases, the burn scar was
      completely excised or reduced in size. Serial tissue expansion should be
      considered as a useful method of reconstruction burns of the head and neck.

PMID- 11451603
TI  - Skin care in burn patients: a team approach.
AB  - Skin care is an important but often neglected issue in burn management. Newly
      healed burn skin is fragile, itchy, dry, and susceptible to sunburn. Without
      proper skin care in burn patients, they may suffer from sleep and mood
      disturbances, depression, and poor compliance to treatment that can jeopardize
      the rehabilitation process. At the Prince of Wales Hospital, skin care has been
      managed since February 1996 by a team consisting of plastic surgeon,
      dermatologist, occupational therapist and nursing specialist. The purpose of this
      study was to evaluate the impact of a skin care program run by a Skin Care Team
      on the rehabilitation of burn patients in a tertiary burn centre. The role of
      different members of the team was also discussed.

PMID- 11451604
TI  - The management of white phosphorus burns.
AB  - Phosphorus burns are a rarely encountered chemical burn, typically occurring in
      battle, industrial accidents, or from fireworks. Death may result even with
      minimal burn areas. Early recognition of affected areas and adequate
      resuscitation is crucial. Amongst our 2765 admissions between 1984 and 1998, 326
      patients had chemical burns. Seven admissions were the result of phosphorus
      burns. Our treatment protocol comprises 1% copper sulfate solution for
      neutralization and identification of phosphorus particles, copious normal saline
      irrigation, keeping wounds moist with saline-soaked thick pads even during
      transportation, prompt debridement of affected areas, porcine skin coverage or
      skin grafts for acute wound management, as well as intensive monitoring of
      electrolytes and cardiac function in our burns center. Intravenous calcium
      gluconate is mandatory for correction of hypocalcemia. Of the seven, one patient
      died from inhalation injury and the others were scheduled for sequential surgical
      procedures for functional and cosmetic recovery. Cooling affected areas with tap
      water or normal saline, prompt removal of phosphorus particles with mechanical
      debridement, intensive monitoring, and maintenance of electrolyte balance are
      critical steps in initial management. Fluid resuscitation can be adjusted
      according to urine output. Early excision and skin autografts summarize our
      phosphorus burn treatment protocol.

PMID- 11451605
TI  - Problems associated with the use of silicone gel sheeting for hypertrophic scars
      in the hot climate of Saudi Arabia.
AB  - Twenty five consecutive Saudi patients who underwent treatment of hypertrophic
      scars using Cica-care silicone gel sheets were included. The scars were secondary
      to burns or traumatic friction injuries. There were 15 females and 10 males with
      a mean age of nine years. Patients were given detailed instructions in applying
      and washing the gel and attended a review clinic regularly. At each visit,
      problems and scar assessment using the Vancouver scale were documented by an
      experienced occupational therapist. Problems associated with gel sheeting were
      common and included persistent pruritus (80%), skin breakdown (8%), skin rash
      (28%), skin maceration (16%), foul smell from the gel (4%), poor durability of
      the sheet (8%), failure of the sheet to improve hydration of dry scars (52%),
      poor patient compliance (12%) and poor response of the scar to treatment (24%).
      Most of these problems were eliminated by temporary interruption of treatment,
      more frequent washings of the gel sheet, better skin hygiene and occasionally by
      changing the brand of gel sheets. Permanent discontinuation of treatment occurred
      in only one patient and was because of lack of response to treatment. The modes
      of action of silicone gel in the treatment of hypertrophic scars are discussed.

PMID- 11451606
TI  - High tension electrical injury from a telephone receiver.
AB  - A high tension (13000 V) electrical injury to a young man from telephone receiver
      is described. The current entered the telephone circuit due to contact with a
      high tension live wire running close to the telephone wire 2 km away from the
      site of incidence.

PMID- 11451607
TI  - Minor [correction of Mi1nor] burns and pneumatocoeles: a case report.
AB  - Minor burns in children need to be cautiously managed as they may manifest with
      life threatening complications especially in the presence of staphylococcal
      infection. A one and a half year old child with minor burns (12% TBSA), who
      developed large pneumatocoeles and peumomediastinum following Staphylococcus
      aureus pneumonia causing severe respiratory distress and needing ventilatory
      support is presented. Most of the pneumatocoeles were spontaneously absorbed over
      a period of 10 days while surgical interference was being contemplated. A
      conservative approach to pneumatocoeles as in non-burn patients may help prevent
      unnecessary surgery. An extensive English literature search (since 1966) did not
      reveal any report of pneumatocoeles in association with burns and therefore we
      believe this to be the first report of its kind.

PMID- 11451608
TI  - Deep dermal burn due to contact with stomach contents.
AB  - A patient sustained deep dermal burns from contact with gastric contents
      following disconnection of his percutaneous endoscopic gastrostomy (PEG) tube. We
      discuss the complications of gastrostomies and add this as a rare complication,
      which may be prevented by a modification to the outlet control of a PEG tube.

PMID- 11451609
TI  - Contact burn by charcoal in an attempted suicide.
AB  - A 23-yr-old lady was inadvertently burned during an attempted suicide. After
      quarrelling with her boyfriend, she attempted to commit suicide by using alcohol,
      benzodiazepine and burning charcoal within her sealed bedroom. Her left leg fell
      over the edge of the bed while she was half-conscious, that resulted in direct
      contact with the hot pot causing 1% full thickness burn and burn of her left
      tibialis anterior and extensor digitorum longus. She was initially resuscitated
      with 100% oxygen and gastric lavage and subsequently was managed in the Burns
      Unit for wound care, surgical debridement of the burn wound and skin graft, and
      psychological support. Burning charcoal in a sealed room is an emerging form of
      suicide in Hong Kong and this is the first case complicated by a burn wound in
      our locality. A holistic approach to tackle the bio-psycho-social aspects of
      individual's problem is advocated.

PMID- 11451610
TI  - Burn wound healing and skin substitutes.
AB  - Burn wound healing is a complex process in the biological objectives and
      mechanisms defined by the initial injury. In this paper the use of keratinocytes
      as a skin substitute is used to illustrate some of the problems associated with
      the development and use of skin substitutes. Skin substitute development must
      always be viewed against the biological and clinical background in order to
      provide maximum assistance to the challenging task of treating burn wounds.

PMID- 11451611
TI  - Design principles for composition and performance of cultured skin substitutes.

PMID- 11451612
TI  - Skin substitutes: a review.

PMID- 11451613
TI  - Clinical evaluation of skin substitutes.

PMID- 11451615
TI  - What factors account for hormone replacement therapy prescribing frequency?
AB  - OBJECTIVES: The purpose of this study was to compare hormone replacement therapy
      (HRT) prescribing frequency to provider characteristics, attitudes and beliefs
      about menopause and HRT. METHODS: There was a mailed survey of providers at a
      large staff-model HMO in Washington state. Participants included 250 family
      practice physicians, 22 gynecologists, and 13 women's health care specialists and
      nurse midwives (83% response rate). The primary outcome, "HRT prescribing
      frequency" (derived from automated pharmacy and visit data) was defined as: the
      total number of estrogen prescriptions written by the provider and filled by
      women aged 50-80 years during the 12 months prior to the survey, divided by the
      number of visits made to the provider by women aged 50-80 years during that same
      12-month period. Covariates included provider characteristics and beliefs about
      menopause and HRT. Logistic regression was used to distinguish providers in the
      upper 40% versus the lower 60% of HRT prescribing frequency. RESULTS: Controlling
      for age and practice type, HRT prescribing frequency was lower among men than
      women providers (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.21-0.65),
      higher among providers who agreed (vs. disagreed or neutral) that a convincing
      scientific case has been made that HRT prevents heart disease (OR 2.66, 95% CI
      1.53-4.61), and higher among those in the upper tertile vs. lower tertiles of an
      HRT encouragement scale (OR 2.50, 95% CI 1.29-4.85). CONCLUSIONS: Female
      providers and providers with positive attitudes toward HRT are the most likely to
      prescribe it.

PMID- 11451616
TI  - Positive aspects of menopause: a qualitative study.
AB  - OBJECTIVE: As a part of a larger study, "Menopause described from the woman's
      perspective", it has been the aim to explore whether women have any positive
      experiences in relation to menopause, and if so, the nature of these experiences.
      METHODS: In a questionnaire, sent to a random sample of 51 year-old Danish women,
      there was included an open-ended question concerning the course of menopause. A
      qualitative approach has been used in the analyses. RESULTS: 393 women have
      answered the open-ended question. One hundred and ninety four women did describe
      positive aspects of menopause. The total number of different quotations with a
      positive content was 268. The answers varied from unspecific statements
      describing a period of well-being or simply a statement of not having problems at
      all, and concrete descriptions which primarily dealt with the relief of ending
      menstruating and attached problems, such as PMS and fear of pregnancy. Finally
      they dealt with the possibility of personal growth and freedom to concentrate on
      own requirements. CONCLUSIONS: The positive aspect of menopause is a relevant
      field to investigate further, quantitatively as well as qualitatively. It is
      recommended that doctors include positive aspects and women's own resources in
      counselling, to avoid medicalization and dis-empowerment in this period of life.

PMID- 11451617
TI  - Early postmenopausal bone loss in hyperthyroidism.
AB  - OBJECTIVES: To evaluate the effect of hyperthyroidism on bone in relation to the
      menopausal state. METHODS: Fifty-nine hyperthyroid (HYPER), 40 hypothyroid
      (HYPO), and 51 control euthyroid (EUTH) women were studied. Bone mineral density
      (BMD) was assessed by dual X-rays absorptiometry (DXA) at the lumbar spine, and
      at the femoral neck. A multi-site QUS device evaluated speed of sound (SOS) at
      the radius (RAD), tibia (TIB), metatarsus (MTR), and phalanx (PLX). Bone markers
      used were serum bone specific alkaline phosphatase (BSAP) and urinary
      deoxypyridinoline (DPD). RESULTS: At all sites, SOS was lower in HYPER than in
      EUTH (RAD P<0.05, TIB P<0.01, MTR P<0.05, PLX P=0.01). The low SOS was only noted
      at the early postmenopausal period. BMD at the femoral neck but not at the lumbar
      spine was lower in HYPER as compared to EUTH (P<0.05). Both femoral neck and
      tibia were the sites with the highest odds ratio for being hyperthyroid (2.3 and
      2.04, respectively). There was no correlation between BMD or SOS and FT(4), TT(3)
      or duration of hyperthyroidism. BSAP and DPD positively correlated with FT(4) and
      TT(3) (P<0.05). CONCLUSIONS: This study suggests that hyperthyroidism affects
      bone mineralization especially during the early postmenopausal period, and the
      effect is mainly at the cortical bone.

PMID- 11451618
TI  - Climacteric vasomotor symptoms do not predict nocturnal breathing abnormalities
      in postmenopausal women.
AB  - OBJECTIVE: To study the association of climacteric vasomotor symptoms and
      nocturnal breathing abnormalities in a sample of healthy postmenopausal women.
      METHODS: Out of 71 postmenopausal women who took part in a large sleep study, 65
      women were included into the present study. Sleep was monitored with
      polysomnography and nocturnal breathing with a static-charge sensitive bed and a
      pulse oximeter. Climacteric vasomotor symptoms were scored daily for 14 days and
      levels of oestradiol and FSH were measured in the serum. RESULTS: Altogether 21
      (32.3%) women had some degree of breathing abnormalities during the study night.
      The occurrence of clinically significant sleep apnoea was low (1.5%) and of
      moderate type (OP-2). In contrast, increased respiratory resistance pattern,
      typical for partial upper airway obstruction, was frequent (16.9%). Seventy-eight
      per cent of the women had arterial oxyhaemoglobin desaturation events, but only
      in 4.6% of the women these events occurred more than 5 times/h of time in bed.
      Older women had more simple periodic breathing (P-1) and lower mean arterial
      oxyhaemoglobin saturation (SaO(2)). Body mass index (BMI) correlated with the
      apnoea frequency (OP-2) and inversely with the mean SaO(2). The severity of
      climacteric vasomotor symptoms or serum oestradiol concentration did not
      correlate with nocturnal breathing abnormalities. CONCLUSIONS: Nocturnal
      breathing abnormalities, especially partial upper airway obstruction, are common
      in postmenopausal women, but climacteric vasomotor symptoms do not predict their
      occurrence or severity. Increasing age and high BMI are important determinants of
      nocturnal breathing abnormalities.

PMID- 11451619
TI  - Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and
      carotid wall artery intima-media thickness.
AB  - AIM: our study assessed whether minor or major hormonal deficiency influenced
      oxidative status and vascular wall structure in menopausal women. METHODS: the
      study series was made up of 62 non hypertensive non diabetic menopausal women
      (mean age 52.3+/-4.7 years) divided into two groups depending on duration of
      menopause (group 1 duration 0-5 years; group 2 duration over 5 years). Total
      cholesterol (TC), LDL cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides
      (TG), malondialdehyde (MDA) and common carotid artery wall intima-media thickness
      (IMT) were determined in the entire series. RESULTS: mean TC, LDL-C, TG, MDA and
      IMT values were higher in group 2 than group 1. The intergroup difference between
      MDA (P<0.007) and IMT values (P<0.006) values was statistically significant.
      CONCLUSIONS: the study revealed a close temporal correlation between plasma
      oxidative stress and carotid wall IMT, jeopardizes vascular wall status as
      menopause proceeds.

PMID- 11451620
TI  - The influence of hormone replacement therapy on skin ageing: a pilot study.
AB  - OBJECTIVES: We studied the effect of hormonal treatment on skin ageing in
      menopausal women. METHODS: Twenty-four patients (45-68 years; mean age, 54.9
      years) without hormone treatment for at least 6 months were included. Patients
      were assigned to three therapy groups: 1, oestrogen only (Estraderm TTS 50)
      (n=6); 2, transdermal oestrogen and progesterone (Estraderm TTS 50 and 0.4 mg
      progesterone vaginal suppository) (n=7); and 3, oral oestrogen and progesterone
      (2 mg Progynova and 0.4 mg progesterone vaginal suppository) (n=8). One group
      without therapy was included as a control group (n=3). Treatment was continued
      for 6 months. Three patients, one from group 2 and two from group 3, discontinued
      therapy before the study endpoint. The following skin parameters were measured at
      monthly intervals during treatment: skin surface lipids, epidermal skin
      hydration, skin elasticity and skin thickness. Concomitant clinical evaluation
      included a subjective clinical evaluation form, a patient questionnaire and
      laboratory tests for oestradiol, progesterone and follicle stimulating hormone.
      RESULTS: Mean levels of epidermal skin moisture, elasticity and skin thickness
      were improved at the end of treatment based on both subjective and objective
      evaluation in patients with hormone replacement therapy (HRT). Skin surface
      lipids were increased during combined HRT, which may reflect stimulatory effects
      of the progestagen component on sebaceous gland activity, while oestrogen alone
      has a sebum-suppressive action. In the HRT groups, the questionnaire for
      climacteric complaints demonstrated significant improvements, while laboratory
      tests showed increases in oestradiol and progesterone and decreases in FSH.
      CONCLUSIONS: HRT with the mentioned regimes significantly improved parameters of
      skin ageing.

PMID- 11451621
TI  - Hormone replacement therapy increases ACTH/dehydroepiandrosterone sulfate in
      menopause.
AB  - OBJECTIVE: To demonstrate that hypoestrogenism in menopause is in part
      responsible for the decrease in circulating dehydroepiandrosterone sulfate (DHEA
      S) and ACTH levels. To test this hypothesis, 25 postmenopausal women aged 47-60
      years, were given orally conjugated equine estrogen (CEE) to study the effect on
      circulating DHEA-S, cortisol and ACTH. DESIGN: A prospective, non-blinded study
      was performed. Hormonal levels were analyzed before and after three cycles of CEE
      0.625 mg/day for 21 days followed each by chlormadinone acetate for 5 days.
      RESULTS: Low baseline levels of DHEA-S increased significantly after HRT (1.71+/
      0.75 to 3.3+/-1.5 micromol/l, (P<0.001). ACTH levels augmented moderately from
      3.26+/-1.4 to 4.7+/-1.8 pmol/l (P<0.05) and cortisol from 350.4+/-118 to 450.8+/
      144 nmol/l (P<0.01). A positive correlation was obtained between 17 beta
      estradiol and ACTH (r=0.48), estradiol and cortisol (r=0.52) as well as estradiol
      and DHEA-S (r=0.60). In addition, the correlation was highly significant
      (P<0.001) between ACTH and DHEA-S at the term of HRT. CONCLUSION: HRT increased
      DHEA-S, ACTH and cortisol concentrations, which may suggest that this therapy may
      exert a stimulatory effect on the pituitary gland when baseline hypoestrogenism
      is present, but further studies are required to clarify the mechanism underlying
      this process.

PMID- 11451622
TI  - Venous endothelial function in postmenopausal women after six months of tibolone
      therapy.
AB  - STUDY OBJECTIVE: To test venous endothelial function in long-term climateric
      therapy with tibolone. DESIGN: Measurement of dorsal hand-vein diameter by venous
      occlusion plethysmography during infusion of norepinephrine (NE), bradykinin
      (BK), NG-monomethyl L-arginine (L-NMMA) and sodium nitroprusside (SNP). SETTING:
      Plethysmography and Menopause Units. University Hospital Valdecilla. Santander.
      Spain. PATIENTS: Eleven postmenopausal women having continuous treatment with
      oral tibolone (2.5 mg/day) for 6 months. INTERVENTIONS: Three plethysmography
      studies were made: at baseline, and at three and six months of treatment. MAIN
      OUTCOME MEASURES: Dorsal hand-vein diameter measured by venous occlusion
      plethysmography during infusion of NE, BK, L-NMMA and SNP. RESULTS: (a) Baseline
      study: maximum dilation with BK was 54.2+/-10.2%. (b) Three-month study: BK
      dilation of 71.5+/-11.9%, with a significant increase of 17.3% (P=0.019) compared
      with baseline. (c) Six-month study: BK dilation of 77.5+/-11.9%, with a
      significant increase 23.3% (P=0.002) compared with baseline. Maximal vasodilation
      was reached with SNP in the three studies and L-NMMA infusion has a similar
      vasoconstrictor response in the three studies. CONCLUSIONS: Long-term climateric
      therapy with tibolone improves vein endothelium-dependent vasodilation suggesting
      a positive impact of this drug on endothelial function.

PMID- 11451623
TI  - Effects of raloxifene and hormone replacement therapy on markers of serum
      atherogenicity in healthy postmenopausal women.
AB  - OBJECTIVE: To determine the effect of raloxifene (RLX) and hormone replacement
      therapy (HRT) on non-high density lipoprotein cholesterol (non-HDL-C) levels and
      the apolipoprotein-B/apolipoprotein-A1 (apo-B/apo-A1) concentration ratio,
      markers of serum atherogenicity, in postmenopausal women. METHODS: Three hundred
      and ninety healthy postmenopausal women aged 45-72 years were enrolled in a
      double-blind, randomized, placebo-controlled, parallel trial at eight outpatient
      sites in the United States. Women were randomly assigned to receive continuous
      combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day
      medroxyprogesterone acetate), 60 or 120 mg/day raloxifene, or placebo for 6
      months. Serum concentrations of non-HDL cholesterol and the apo-B/apo-A1
      concentration ratio were measured in serum samples obtained at baseline and at 6
      months of treatment. RESULTS: At 6 months, non-HDL-C and apo-B/apo-A1 were
      significantly reduced by 60 mg/day RLX (10 and 11%, respectively), 120 mg/day RLX
      (9 and 12%, respectively) and HRT (10 and 12%, respectively), compared with
      placebo. The effect of all treatments to lower non-HDL-C and apo-B/apo-A1 was
      greatest in women with hypercholesterolemia (total-C>240 mg/dl) at baseline.
      Among women with undesirable (>160 mg/dl) non-HDL cholesterol at baseline, RLX
      and HRT lowered the percentage of these women remaining above this threshold
      after 6 months (placebo, 89%; 60 mg/day RLX, 61%; 120 mg/day RLX, 74%; HRT, 58%).
      Similar results were observed for women with high (>190 mg/dl) non-HDL
      cholesterol at baseline. CONCLUSION: In healthy postmenopausal women, RLX and HRT
      lower serum non-HDL-C and apo-B/apo-A1, indicators of serum atherogenicity, to a
      similar extent.

PMID- 11451624
TI  - Pelvic actinomycosis in menopause: a case report.
AB  - OBJECTIVE: To examine the association between the use of intra uterine device
      (IUD) and the risk of actinomycosis in postmenopausal women. METHODS: We report a
      case of pelvic actinomycosis in a postmenopausal woman who was wearing an IUD for
      14 years until 20 months after the beginning of menopause. In the last 5 years
      the patient had been suffering occasionally from pain, abdominal tension and
      rectal tenesmus. The disease was revealed clearly 18 months after removing the
      intrauterine device. RESULTS: The diagnosis of pelvic actinomycosis was only
      possible after hysterectomy, bilateral oophorectomy and multiple biopsies. At
      histological features a focus with actynomycetes colonies was evident.
      CONCLUSIONS: This study supports the previously reported association between the
      pelvic location of actinomycosis and the use of the IUD. The removal of IUD
      should be mandatory in postmenopausal women.

PMID- 11451625
TI  - Knowledge, attitudes and management strategies in Scandinavia concerning hormone
      replacement therapy: a comparison between gynecologists in Denmark, Norway and
      Sweden.
AB  - OBJECTIVES: To describe and compare attitudes, knowledge and management
      strategies concerning the prescription of hormone replacement therapy (HRT)
      between gynecologists from three Scandinavian countries. DESIGN AND METHODS: In a
      cross-sectional study gynecologists in Denmark (n=386), Norway (n=475) and Sweden
      (n=1323) were invited by letter to complete and return an enclosed questionnaire.
      Then 1653 of the 2184 (76%) contacted gynecologists completed and returned the
      questionnaire. RESULTS: of the 1653 Scandinavian gynecologists, 42% offered HRT
      to all women provided there was no contraindication, while 58% recommended HRT to
      selected women after considering the advantages and disadvantages of HRT. In
      Norway and Sweden, the proportion of gynecologists routinely prescribing HRT for
      women without contraindications increased with age and in the oldest age group of
      gynecologists (>55 years) 49 and 56%, respectively, recommended HRT to all women.
      The gynecologists were unanimous in their choice of the type of HRT for
      perimenopausal women as 94% preferred cyclical or sequential combined
      (estrogen/progestogen) treatment or estrogen monotherapy (orally or
      transdermally) for hysterectomized women (95%). For postmenopausal women, 75% of
      the gynecologists offered continuous combined HRT while cyclical combined therapy
      was chosen by 15% of the gynecologists. No significant differences were found
      between physicians in the three countries regarding indications and
      contraindications to HRT. CONCLUSIONS: Scandinavian gynecologists are generally
      well informed concerning HRT and liberally recommend HRT for women without
      contraindications.

PMID- 11451627
TI  - Application of sorption--desorption moisture transfer modeling to the study of
      chemical stability of a moisture sensitive drug product in different packaging
      configurations.
AB  - The sorption--desorption moisture transfer (SDMT) model was used to predict the
      effect of desiccant quantity, tablet quantity and tablet initial moisture content
      on the relative humidity inside high density polyethylene (HDPE) bottles
      containing a moisture sensitive drug product, roxifiban tablets. The effect of
      these variables on the stability of roxifiban tablets in the HDPE bottles was
      also evaluated. There was a good correlation between the calculated relative
      humidity values inside the package and stability results. Tablet degradant
      concentration increased with the increase in the relative humidity calculated by
      the SDMT model. Desiccant quantity was the most important factor in controlling
      degradation rate, which decreased as the quantity of desiccant in the bottle was
      increased. For a given desiccant quantity, degradation rate increased with an
      increase in the weight of tablets in the bottle. The inclusion of a desiccant in
      the package significantly reduced the effect of initial tablet moisture content
      on stability. Nevertheless, the effect of initial moisture content was still
      discernible. This study demonstrated the practical utility of the SDMT model in
      understanding the correlation between packaging variables and the stability of a
      moisture sensitive product.

PMID- 11451628
TI  - Dry powder inhalation of liposomal Ketotifen fumarate: formulation and
      characterization.
AB  - The purpose of the experiment was to formulate and characterize the dry powder
      inhalation (DPI) formulation of liposomally entrapped anti-asthmatic drug,
      Ketotifen fumarate (KF). Liposomes composed of saturated egg phosphatidyl choline
      (EPC) and cholesterol (CHOL) were prepared by lipid film hydration and sonicated
      to have the desired size (<5 microm). Process variable such as vacuum,
      presonication hydration, postsonication hydration, purification and lamellae
      composition, were optimized for encapsulation efficiency of KF. Liposomal
      dispersion was blended with cryoprotectant (sugar) in varying bulk and mass
      ratios and assessed for its influence on retention of encapsulated drug on
      lyophilization. Characterization of liposomal dispersion was done for size,
      lamellarity, entrapped volume and oxidation index. DPI formulation was
      characterized for angle of repose, compressibility index, dispersibility and
      respirable fraction (British Pharmacopoeia, apparatus A). Process optimization
      revealed that a vacuum, 20 in.; presonication hydration, 60 min; postsonication
      hydration, 2 h and purification by dialysis gave maximum encapsulation
      efficiency. Sucrose was found to be the most suitable cryoprotectant at bulk
      strength of 500 mM and mass ratio of lipid/sugar, 1/12. Blending of sorbolac
      before lyophilization showed better retention of encapsulated KF (97.92+/-0.54%).
      In the preparation of sonicated MLVs, the presence of nitrogen atmosphere, alpha
      tocopherol and EDTA could not totally eliminate EPC oxidation, expressed as the
      change in oxidation index from 0.427+/-0.01 to 1.510+/-0.01. The respirable
      fraction of the developed formulation (21.59+/-1.53%) is comparable with the
      control (26.49+/-1.52%). From studies, it may be concluded that an optimal bulk
      and mass ratio of sucrose, relative to the size of liposomes is necessary for
      effective cryoprotection. In this investigation, DPI of liposomal KF was
      successfully prepared and delivered to the required site in the lungs.

PMID- 11451629
TI  - Cross-linking chitosan-Fe(III), an oral phosphate binder: studies in vitro and in
      vivo.
AB  - The objective was to evaluate the in vitro and in vivo phosphate binding
      properties of cross-linked chitosan iron (III) (CH-Fe(III)-CL), a potential oral
      phosphate binder for treating hyperphosphatemia. At equilibrium, the in vitro
      phosphate binding of CH-Fe(III)-CL was 23.6 mg g(-1) for simulated
      gastrointestinal conditions. In hyperphosphatemic rats, CH-Fe(III)-CL was similar
      to iron sulfate in reducing serum phosphate by about 35%.

PMID- 11451630
TI  - Examination of oxidized cellulose as a macromolecular prodrug carrier:
      preparation and characterization of an oxidized cellulose-phenylpropanolamine
      conjugate.
AB  - The purpose of this study was to investigate the use of 6-carboxycellulose (OC),
      a biocompatible and bioresorbable polymer, as a prodrug carrier for amine drugs.
      Phenylpropanolamine hydrochloride (PPA.HCl) was used as a model drug. OC and PPA
      were reacted in dimethylformamide (DMF) in the presence of 1,3
      dicyclohexylcarbodiimide (DCC) for 2.5 days at room temperature. Filtration,
      followed by washing with methanol, and subsequent drying under vacuum, produced
      the conjugate in 65-78% yield. The amount of PPA in the product, determined from
      the difference in the carboxylic content before and after the reaction, was 24.2%
      (w/w), corresponding to a degree of substitution (DS) value of 0.7. The Fourier
      transform-infra red (FT-IR) spectrum of the conjugate, compared with that of OC
      and PPA.HCl, showed a new band at about 1533 cm(-1) attributable to a C = O
      (amide II) stretching and N single bond H (amide I and amide II) bending
      vibrations, a decrease in intensity of the characteristic free carboxylic acid
      carbonyl stretching band at about 1748 cm(-1), and a strong band at 1663 cm(-1)
      due to C = O (amide I) stretching vibration, suggesting that the OC is linked to
      PPA via an amide bond. The solid-state carbon-13 cross polarization/magic angle
      spinning nuclear magnetic resonance ((13)CCP/MAS NMR) spectrum of the conjugate
      was also consistent with this structure. The release studies performed in pH 4.5,
      5.5, and 7.4 buffer solutions and in rat liver homogenate (pH 7.4), showed the
      conjugate to be more susceptible to hydrolysis at a lower pH and in the presence
      of rat liver homogenate. In conclusion, the results presented show that OC can be
      covalently linked to amine drugs via an amide bond in DMF using DCC as a coupling
      agent, and provide a macromolecular prodrug delivery system.

PMID- 11451631
TI  - Stability indicating HPLC method for the estimation of oxycodone and lidocaine in
      rectal gel.
AB  - An HPLC method for the quantification of oxycodone and lidocaine in a gel matrix
      is described. The mobile phase consisted of methanol--water--acetic acid (35:15:1
      v/v/v) and was delivered at 1.5 ml/min through a 4.6 x 250 mm Zorbax SB-C8
      column. Oxycodone was detected at 285 nm and lidocaine at 264 nm. Linear
      calibration curves were obtained for oxycodone in the range of 0.05--1.5% (w/w)
      and for lidocaine in the range of 0.1--5.0% (w/w). Oxycodone and lidocaine were
      treated with hydrogen peroxide and the oxidation products were readily separated
      on the column. The method was applied to assess the stability of a gel containing
      oxycodone hydrochloride (0.3% w/w) and lidocaine (1.5% w/w). The gel was stored
      under refrigeration in ready-to-use syringes and under these conditions oxycodone
      and lidocaine were stable for at least 1 year. The gel is useful in the
      management of tenesmus in rectal cancer.

PMID- 11451632
TI  - Filter extrusion of liposomes using different devices: comparison of liposome
      size, encapsulation efficiency, and process characteristics.
AB  - Liposomes were prepared by stepwise extrusion through 5, 1, 0.4, 0.2, 0.1 and
      0.05 microm pore sizes using two different filter-extruders, the continuous high
      pressure device Dispex Maximator (CE) or alternatively the discontinuous Avestin
      LiposoFast (DE). The liposome dispersions obtained were compared in terms of
      particle size, lamellarity and encapsulation efficiency of calcein. The liposomes
      were smaller with CE than DE at all stages due to higher flow rates and pressure
      drops, except for final filter pore size (0.05 microm) where both preparations
      had similar sizes. The particle size analysis technique itself had a strong
      influence on the liposome sizes measured. For bigger liposomes (extruded through
      0.4 microm filters) the Nicomp 370 revealed bigger volume-based mean particle
      sizes along with more stringent differences between volume-based and number-based
      diameters than the Malvern Zetasizer. In contrast, for small liposomes extruded
      through 0.05 microm filters, similar liposome sizes were found no matter which of
      the two PCS techniques or cryo-transmission electron microscopy was used. In
      congruence to the liposome sizes measured, encapsulation efficiencies were
      smaller for CE than DE at all filter stages except the final (0.05 microm). No
      lipid loss occurred and lyso-phosphatidylcholine formation was negligible
      irrespective of which extrusion technique was used.

PMID- 11451633
TI  - A new recombinant human bone morphogenetic protein-2 carrier for bone
      regeneration.
AB  - A gelatin sponge was formed by foaming and heat treating a gelatin solution,
      followed by coating the solid with poly(D,L-lactic-co-glycolic acid) to reinforce
      the gelatin framework. This sponge was tested for its suitability as a
      biodegradable porous, recombinant human bone morphogenetic protein (rhBMP)-2
      carrier. Incorporation of rhBMP-2 into the sponge was closely related to its bulk
      density of gelatin sponge. The calcium content in the sponges, as assessed by an
      ectopic bone formation assay in rats, increased with the increasing sponge bulk
      density. Histologic and peripheral quantitative computed tomography analysis of
      implants in this ectopic assay system revealed cell growth throughout the carrier
      in 4 weeks after implantation regardless gelatin bulk density. The carrier
      containing rhBMP-2 maintained its three-dimensional structure after implantation;
      the carrier resisted collapse caused by soft tissue pressure during rapid bone
      formation as assessed by soft X-ray photographs. These results indicate that this
      newly developed sponge has excellent carrier characteristics to introduce rhBMP-2
      into areas needed for bone regeneration.

PMID- 11451634
TI  - Effect of salt form on chemical stability of an ester prodrug of a glycoprotein
      IIb/IIIa receptor antagonist in solid dosage forms.
AB  - The effect of salt form on the stability of an ester prodrug of a IIb/IIIa
      receptor antagonist was investigated. The pH of maximum stability for the ester
      prodrug is approximately 4. The mesylate salt is thought to provide lower
      microenvironment pH, closer to the pH of maximum stability, than the acetate
      salt. Stability of drug product manufactured using the mesylate salt (DMP 755)
      was studied and compared with that for the acetate salt (DMP 754). Formulations
      contained disodium citrate as a pH modifier to control formulation pH, since
      solid state stability for this compound is dependent on the microenvironment pH.
      The pH modifier was not able to achieve adequate microenvironment pH control for
      the DMP 754 drug product when added using a dry manufacturing process. While DMP
      754 required the use of a pH modifier added in solution during wet granulation in
      order to improve drug product stability, DMP 755 was able to achieve similar
      results using the dry granulation process. Stability of DMP 755 drug product was
      independent of effectiveness of the pH modifier. This study showed that the
      choice of the salt form may provide an alternative for maximizing drug product
      stability.

PMID- 11451635
TI  - Production of aqueous shellac dispersions by high pressure homogenisation.
AB  - The use of shellac for coating purposes in pharmacy, food and nutriceutical
      industry generally involves the use of organic solvents. An aqueous shellac
      dispersion has been developed by applying high pressure homogenisation. Shellac
      was dissolved in alkaline solution, precipitated by HCl addition and the obtained
      suspension homogenised at 1500 bar applying 20 cycles. The volume diameter 50%
      was 2 microm, a distinct fraction of particles was in the nanometer range. This
      surfactant-free shellac dispersion with 20% solid content proved to be physically
      stable and showed good film forming properties.

PMID- 11451636
TI  - Application of reinecke salt and alizarin S for the determination of promazine.
AB  - Reinecke salt and alizarin S have been tested as reagents for the determination
      of promazine. They react in neutral and acidic media with promazine forming a
      reddish and brown crystalline compounds. The compounds are sparingly soluble in
      water but fairly soluble in acetone and methanol. The quantitative extraction of
      compound of promazine with alizarin S has been used for the extractive
      spectrophotometric determination of promazine. Formation of promazine ion
      association complex with Reinecke salt has been applied for indirect
      determination of low concentrations of promazine by AAS measurement of the
      chromium content of the reineckate counter - anion.

PMID- 11451637
TI  - A sensitive method for the determination of gemfibrozil in human plasma samples
      by RP-LC.
AB  - A sensitive high-performance liquid chromatographic assay for the quantitative
      determination of gemfibrozil is described in this work. Ibuprofen was used as
      internal standard. The assay involved a single cyclohexane extraction and LC
      analysis with fluorescence detection. Chromatography was performed at 40 degrees
      C on a Hypersil ODS column. The mobile phase was a mixture of a solution of
      phosphoric acid 0.4% and acetonitrile (45:55). The method was validated. The
      detection limit of this method was 0.025 microg ml(-1); only 0.5 ml of the plasma
      sample was required for the determination. The calibration graph was linear from
      0.05 to 0.5 microg ml(-1) and required a cubic equation from 0.5 to 30 microg ml(
      1). Intra and inter-day precision (C.V.) did no exceed 15%. Mean recoveries were
      of 90.15+/-6.9% (C.V.'s<8%) for gemfibrozil and 93.10% for ibuprofen
      Applicability of the method was demonstrated by a pharmacokinetic study in normal
      volunteers who received gemfibrozil by oral route.

PMID- 11451638
TI  - Simultaneous determination of codeine and ethyl morphine HCL in tablet
      formulations using LC.
AB  - A reverse phase high performance liquid chromatography (HPLC) method was
      developed for the simultaneous determination of codeine (methyl morphine) and
      dionin (ethyl morphine hydrochloride) in antitussive analgesic tablet
      formulations. A C(18) column and methanol-water (1:2) mixture mobile phase (pH
      3.0) were used. Spectrophotometric detection was carried out at 210 nm. The total
      elution time was shorter than 7 min. This method was found to be quite precise
      and reproducible. This proposed method was successfully applied to the
      determination of codeine and ethyl morphine hydrochloride in tablets produced by
      the Turkish Army Drug Factory.

PMID- 11451639
TI  - Differential-pulse adsorptive stripping voltammetric determination of the
      antibacterial lomefloxacin.
AB  - A differential-pulse adsorptive stripping voltammetric method for the
      determination of trace amounts of the antibacterial lomefloxacin is proposed. By
      using an accumulation potential of -0.30 V and a 2 min accumulation time, the
      linear concentration range of application was 1.0-10.0 ng ml(-1) of lomefloxacin,
      with a relative standard deviation of 3.8% (for a level of 5.0 ng ml(-1)) and a
      detection limit of 0.3 ng ml(-1). The method was applied to determination of
      lomefloxacin in human urine and serum samples. It was validated using HPLC as a
      reference method. Recovery levels of the method reached 100% in all cases.

PMID- 11451640
TI  - LC separation of calcipotriol from its photodegradation products and protection
      possibilities using adjuvants.
AB  - Mobile phase optimization and reversed-phase column characteristics were used to
      separate photodegradation products from the parent compound, 24-cyclopropyl-9-,10
      secochola-5,7,10(19),22-tetraene-1alpha,3beta,24-triol (calcipotriol). Separation
      between calcipotriol and its degradation products was obtained with an
      acetonitrile/water (53:47, v/v) mobile phase on a C(18) Hypersil ODS column (250
      mm length, 4.6 mm id, 5 microm particle size) and a flow rate of 1 ml/min. Using
      this system, the influence of commonly used solvents in dermatology on
      degradation was studied. The addition of a UV filter in two concentrations was
      also evaluated for its possible protective effect to light exposure. Propylene
      glycol and polyethylene glycol 400 decreased the speed of degradation. The
      sunscreen 2-hydroxy-4-methoxybenzophenone affords a protection proportional to
      the filter concentration used in the study.

PMID- 11451641
TI  - Comparison of spectrophotometric and an LC method for the determination
      perindopril and indapamide in pharmaceutical formulations.
AB  - A new sensitive, simple, rapid and precise reversed-phase high performance liquid
      chromatographic (HPLC) and two spectrophotometric methods have been developed for
      resolving binary mixture of perindopril and indapamide in the pharmaceutical
      dosage forms. The first method is based on HPLC on a reversed-phase column using
      a mobile phase of phosphate buffer pH 2.4 and acetonitrile (7:3 v/v) was used.
      Linearity range for perindopril and indapamide was 5.0-70.0 and 8.0-35.0 microg
      ml(-1). In the second method, the first derivative spectrophotometry with a zero
      crossing technique of measurement is used for the simultaneous quantitative
      determination of perindopril and indapamide in binary mixtures without previous
      separation step. Linear calibration graphs of first derivative values at 225.7
      and 255.4 nm for perindopril and indapamide, respectively. The third method is
      based on ratio derivative spectrophotometry, the amplitudes in the first
      derivative of the ratio spectra at 226.5 and at 255.3 nm were selected to
      determine perindopril and indapamide in the binary mixture. All the proposed
      methods showed good linearity, precision and reproducibility. The proposed
      methods were successfully applied to the pharmaceutical dosage forms containing
      the above-mentioned drug combination without any interference by the excipients.

PMID- 11451642
TI  - A sensitive chemiluminescent enzyme immunoassay for the bioanalysis of carboxyl
      terminal B-chain analogues of human insulin.
AB  - Quantification of analogues of human insulin in biological matrices is
      complicated by differences in their immunoreactivity and the presence of both the
      analogue and endogenous concentrations of insulin in test samples. To facilitate
      pharmacokinetic comparisons of carboxyl-terminal B-chain analogues of human
      insulin, we undertook development of a sensitive ELISA. The ELISA detection
      method was optimized systematically to permit routine analysis of 10-microl serum
      samples. Accordingly, a noncompetitive 'sandwich' chemiluminescent ELISA was
      validated for the quantification of carboxyl-terminal B-chain insulin analogues
      in human serum over a concentration range from 5 to 3125 pM. The mean bias (RE%)
      within the validated range varied from -10.3 to 4.3%, with an intermediate
      precision (inter-assay CV%) from 4.2 to 11.5%. The two-sided 90% expectation
      tolerance interval for total measurement error was within +/-25% of the nominal
      concentration for all levels of validation samples. Insulin lispro, human
      insulin, proinsulin, despentapeptide insulin (DPI) and porcine insulin displayed
      comparable crossreactivity in the ELISA. Potential utility of the new assay for
      insulin bioanalysis in nonhuman species was investigated by assessing the
      pharmacokinetic profile of DPI in rats following administration of a single
      subcutaneous dose. The sensitive chemiluminescent detection method is simple to
      perform and should be readily adaptable for ELISAs of other therapeutic proteins.

PMID- 11451643
TI  - Quantifying amorphous content of lactose using parallel beam X-ray powder
      diffraction and whole pattern fitting.
AB  - The objective of this study was to demonstrate the applicability of parallel beam
      X-ray powder diffraction (XRPD) and a new method for whole pattern fitting to the
      quantification of the residual amount of amorphous content in a pharmaceutical
      solid using lactose as a model system. Lactose monohydrate, prepared by slurry
      conversion of anhydrous lactose, was mixed with different amounts of amorphous
      lactose produced by lyophilization. X-ray powder diffractograms of each mixture
      were recorded and analyzed by whole pattern fitting using Percentage
      Crystallinity Determination Software from Kratos Analytical Inc. The
      polycapillary X-ray optic, which provides a parallel beam of X-radiation, has
      advantages over Bragg-Brentano Optics with respect to sample height artifacts.
      Significant shifts in peak position with changes in sample height of lactose
      monohydrate were observed using Bragg-Brentano Optics while no change was
      detected for the polycapillary X-ray optic. A technique to normalize all
      diffractograms to have the same total integrated intensity was necessary to
      eliminate tube fluctuation effects. After normalization, the amorphous content of
      lactose in the range of 1-10% was reproducibly predicted (small standard
      deviation between samplings) using whole pattern fitting. The limit of detection
      was calculated to be 0.37% amorphous content. The results indicated that parallel
      beam XRPD and whole pattern fitting can provide accurate analysis of relatively
      small amounts of amorphous content in pharmaceuticals compared to typical XRPD
      analysis.

PMID- 11451644
TI  - Near-infrared spectroscopy as a convenient analytical method for alkyl
      polyglycosides.
AB  - Near infrared (NIR) spectroscopy is used for the rapid determination of decyl
      glucopyranoside (10G1) and alkyl polyglycoside (AG) mixtures having different
      alkyl chain length and the number of glucose unit in aqueous solution. NIR
      spectroscopy is a much simpler spectroscopic analysis method compared to three
      analytical methods for mixture of AGs such as thin layer chromatography (TLC),
      high performance liquid chromatography (HPLC), and photometry method. NIR spectra
      of AGs between 0.030 and 0.540 mg/ml in aqueous solutions were utilized to
      develop a calibration model. Both raw spectra and the second derivatives of AGs
      were tested for the best fit. The best calibration was built with second
      derivative spectra by using multiple linear regression (MLR). The standard error
      of calibration (SEC) and the standard error of prediction (SEP) were used for the
      evaluation of the model. The best calibration provides an SEP of 0.052 and 0.061
      mg/ml for the prediction set of 10G1 and AG mixture, respectively.

PMID- 11451645
TI  - Variation of free phenolic acids in medicinal plants belonging to the Lamiaceae
      family.
AB  - Ten species belonging to the family Lamiaceae and representing the most popular
      medicinal plants used in Polish phytotherapy were examined for the content of
      free phenolic acids (PhAs). Two depsides, rosmarinic and chlorogenic acids, as
      well as eight simple PhAs, protocatechuic, gentisic, p-hydroxybenzoic, caffeic,
      vanillic, syringic, p-coumaric and ferulic acids, in different qualitative and
      quantitative proportions depending on the plant examined were determined by the
      rapid, selective and accurate method combining solid-phase extraction and high
      performance liquid chromatography.

PMID- 11451646
TI  - Solid-phase extraction and simplified high-performance liquid chromatographic
      determination of 10-deacetylbaccatin III and related taxoids in yew species.
AB  - Solid-phase extraction was accomplished with specially prepared cartridges filled
      with silanised silica gel (RP-2) for the purpose of 10-deacetylbaccatin III (10
      DAB III) and related taxoids extracts purification obtained from different yew
      materials. In the first method, the analysed taxoids eluted in 75% methanol, but
      in the second method, the preliminary elution with 30% methanol was made. DAB III
      and its six derivatives were separated from co-extractives in merely acetonitrile
      water gradient mode during 25 min on Waters Symmetry C-18 column with photodiode
      array (PDA) detection. The total recoveries for 10-DAB III and paclitaxel in the
      first SPE method (all compounds were applied in amounts of 80 microg) were about
      98 and 94%, respectively. Almost 100% recoveries for paclitaxel and baseline
      separation of 10-DAB III and co-extracted compounds were obtained when
      preliminary elution with 30% methanol was performed. This method can be applied
      as a routine, inexpensive and uncomplicated procedure for 10-DAB III and related
      taxoids determination in yew material.

PMID- 11451647
TI  - Automatic multicommmutated flow system for diffusion studies of pharmaceuticals
      through artificial enteric membrane.
AB  - An automatic flow procedure with spectrophotometric detection was developed for
      the study of pharmaceuticals diffusion through an artificial enteric membrane.
      The manifold comprised two independent flow pathways, gathered by a diffusion
      unit with two compartments and an enteric lipophilic membrane. The pathways were
      automatically filled with solutions simulating digestive and plasmatic conditions
      by means of four solenoid valves. The diffusion of pharmaceuticals from the
      enteric to the plasmatic compartment was performed in closed loop pathways, and
      was continuously monitored by a flow cell coupled to the acceptor solution
      pathway. The volumes of the digestive and plasmatic solutions were 6.0 and 3.6
      ml, respectively, which comprised filling unit compartment, pumping tubing and
      connecting flow lines. Pumping flow rates of donor and acceptor solutions were
      maintained at 6.0 and 2.5 ml min(-1), respectively. The proposed system was
      employed in diffusion studies of caffeine and aminophylline, and in the
      evaluation of the influence of tensioactive agents on the diffusion process.
      After continuous solutions circulation for 60 min, caffeine concentration in the
      acceptor stream was ca. 18% of its initial concentration at the digestive
      compartment. The system could be programmed to perform several replicates,
      stopping them with different degrees of diffusion without operator assistance.
      The data generated by the spectrophotometer was read by the microcomputer as a
      time function, and stored for further mathematical treatment.

PMID- 11451648
TI  - Comparative evaluation of the flavonoid content in officinal Tiliae flos and
      Turkish lime species for quality assessment.
AB  - Lime flowers are used for various medicinal purposes in phytotherapy. Flavonoids,
      volatile oil and mucilage components are known as the active ingredients. In
      European Pharmacopoeia (EP), a simple thin-layer chromatographic (TLC) technique,
      which based on the analysis of the flavonoid composition was defined for the
      qualitative analysis of the drug. In this study, flavonoid composition in the
      flowers, bracts and leaves of the officinal species, Tilia platyphyllos were
      studied using a reversed-phase high performance liquid chromatographic (HPLC)
      technique, in order to develop a rapid, reliable and accurate method for
      quantitative analysis. The results were further compared with in those parts of
      two common species growing in Turkey, Tilia rubra and Tilia argentea. Results of
      the present study revealed that flavonoid composition of each lime species
      possesses a specific fingerprint HPLC chromatogram depending upon the parts used
      and evaluation of the data might be helpful in the quality assurance as well as
      determination of adulteration of the crude drug.

PMID- 11451649
TI  - An enantioselective assay for (+/-)-modafinil.
AB  - Enantiomers of modafinil, (diphenylmethyl)sulphinyl-2-acetamide, were separated
      by an amylose tris[(S)-1-phenylethylcarbamate] chiral stationary phase, using
      acetonitrile: water (25:75 v/v) as mobile phase, with excellent selectivity
      (alpha=1.4) and resolution factors (R(s)=1.5). The assay involved a solid-phase
      extraction of the enantiomers of modafinil from plasma using a C(18) Cartridge. A
      good linear relationship was obtained in the concentration of 0.15-3 microg ml(
      1) for each enantiomer. The method developed is sufficiently accurate and precise
      to be used for clinical samples and has a good selectivity with the two main
      circulating metabolites: the (diphenylmethyl)sulphinyl-2-acetic acid and
      (diphenylmethyl)sulphonyl-2-acetamide. The use of a polysaccharide-based column
      on multimodal elution was explored in developing the method.

PMID- 11451650
TI  - An ion exchange liquid chromatography/mass spectrometry method for the
      determination of reduced and oxidized glutathione and glutathione conjugates in
      hepatocytes.
AB  - A rugged LC-MS/MS method was developed to quantify reduced and oxidized
      glutathione (GSH and GSSG, respectively) in rat hepatocytes. In addition, GSH
      conjugates can be detected, characterized and measured in the same analysis.
      Samples were treated with acetonitrile and iodoacetic acid to precipitate
      proteins and trap free GSH, respectively. These highly polar analytes were
      separated by ion exchange chromatography using conditions that were developed to
      be amenable to electrospray ionization and provide baseline chromatographic
      resolution. A solvent gradient with a total run time of 13 min was used to elute
      the analytes, as well as any highly retained components in the samples that would
      otherwise accumulate on the HPLC column and degrade the chromatography. The
      analytes were detected using either selected ion monitoring (SIM) using an ion
      trap mass spectrometer or selected reaction monitoring (SRM) using a triple
      quadrupole mass spectrometer. The ranges for quantification of GSH and GSSG using
      an ion trap were 0.651-488 microM and 0.817-327 microM, respectively. Using SRM
      with the triple quadrupole instrument, the ranges of quantification for GSH and
      GSSG were 0.163-163 microM and 0.0816-81.6 microM, respectively. The accuracy and
      precision for both methods were within 15%. The utility of the method was
      demonstrated by treating rat hepatocytes with model compounds menadione and
      precocene I. Menadione, which contains a quinone moiety that undergoes redox
      cycling and induces concentration- and time-dependent oxidative stress in
      hepatocytes, resulted in decreased GSH concentrations with concomitant increase
      in concentrations of GSSG, as well as a GSH-menadione conjugate. When hepatocytes
      were incubated with precocene I, a time-dependent decrease in GSH concentrations
      was observed with concomitant increase in a GSH-precocene conjugate. GSSG
      concentrations did not increase in the presence of precocene I, consistent with
      its lack of redox activity. This analytical method has general utility for
      simultaneously investigating the potential of test compounds to induce both
      oxidative stress from redox cycling in vitro and the formation of GSH conjugates.

PMID- 11451651
TI  - A fast and efficient determination of amines and preservatives in cough and cold
      liquid and suspension formulations using a single isocratic ion-pairing high
      performance [correction of power] liquid chromatography method.
AB  - A single, highly selective ion-pairing reverse phase-high power liquid
      chromatography (RP-HPLC) method has been developed for the determination of
      amines and preservatives in a wide range of Tylenol((R)) liquid and suspension
      liquid products. As with many OTC products, the challenge is to quantitatively
      extract the analytes from difficult matrices and specifically analyze them in the
      presence of various excipients and flavors. Historically, separate analytical
      methods were used for each class of analytes (acids, bases and neutral
      compounds). In this method a mobile phase consisting of a buffered ion-pairing
      agent with acetonitrile, methanol and tetrahydrofuran was used to separate the
      charged amines from neutral and acidic compounds on a Phenomenex LUNA C8(2) 75 x
      4.6 mm i.d. analytical column with a 3-microm particle size. The analytes include
      acids (benzoic acid), bases (pseudoephedrine, chlorpheniramine, dextromethorphan,
      doxylamine and diphenhydramine) and a neutral compound (butylparaben). The
      effects of pH, the chain length of the ion-pairing reagent, ionic strength and
      organic modifiers on the separation are discussed. The method is linear from 15
      to 150% of the target amounts. The optimized method proves to be specific, robust
      and accurate for the analysis of the compounds.

PMID- 11451652
TI  - Spectrophotometric determination of cetylpyridinium chloride in pharmaceutical
      products.
AB  - The aim of this work is to study the formation of chelate compound of strontium
      (Sr(II)) with bromopyrogallol red (BPR) and cetylpyridinium chloride (CPC) and to
      develop a simple, rapid and sensitive method for spectrophotometric determination
      of CPC in pharmaceutical products, based on the influence of micellar media on
      the absorption spectra of the complex of Sr(II) with BPR. The formation of the
      ternary complex (Sr(II)-BPR-CPC) is accompanied by a marked increase in the
      absorbance and a bathochromic shift in the maximal absorption of the complex from
      555 to 627.5 nm, hence, there is a difference (Deltalambda=lambda(Sr) (BPR) (CPC)
      lambda(Sr) (BPR)=72.5 nm) and large hyperchromic shift in lambda(max)
      (DeltaA=A(Sr) (BPR) (CPC)-A(Sr) (BPR)=0.258), and the ternary complex is stable
      for at least 2 days. The optimum pH range for the reaction is 4.0-5.0 and Beer's
      law is obeyed over the concentration range 0.01-0.07 mg/ml. The method has been
      successfully applied to the direct determination of cetylpyridinium chloride in
      pharmaceutical product where excellent agreement between reported and obtained
      results were achieved. The relative standard deviation was better than 1% in all
      cases.

PMID- 11451653
TI  - Determination of active component in silymarin by RP-LC and LC/MS.
AB  - Silybin, isosilybin, silydianin and silycristin in silymarin were separated and
      quantitatively determined by RP-HPLC. Two diastereoisomers of silybin and
      isosilybin were respectively separated by RP-HPLC and confirmed by LC/MS.
      Chromatographic condition consisted of column: Shim-pack VP-ODS (150 x 4.6mm i.d.
      5 microm) and Pre-column (10 x 4.6 mm i.d. 5 microm); mobile phase: methanol and
      solvent mixture (water: dioxane=9:1) by gradient; flow rate: 1.5ml/min; column
      temp.: 40 degrees C; detector wavelength: 288 nm; The recovery of 99.66% for
      silycristin, 99.48% for silydianin, 100.0% for silybin and 98.72% for isosilybin
      was respectively obtained.

PMID- 11451654
TI  - Application of Prussian blue-based optical sensor in pharmaceutical analysis.
AB  - Optical flow-through cell-detector with incorporated transparent chemosensitive
      layer of Prussian blue has been applied in simple, single-channel flow-injection
      system for pharmaceutical analysis. The reductant analyte converts the Prussian
      blue based sensing layer to Prussian white form, and the attendant color change
      is used for sensing. Discoloration of the film is spectrophotometrically detected
      at 720 nm wavelength. The flow injection system has been successfully used for
      selective determination of ascorbic acid in simple and complex pharmaceuticals.
      The method is free from interferences caused by various ions and active
      ingredients commonly found in pharmaceuticals. The flow-through sensor is useful
      for spectrophotometric flow-injection analysis of intensively colored and turbid
      samples. The results of medicine analysis are comparable to those obtained using
      reference pharmacopeal method. The analytical system could be also used for
      determination of cysteine and hydrogen peroxide in medicines.

PMID- 11451655
TI  - The respiratory burst response of surface-adhering leukocytes. A key to tissue
      engineering.
AB  - Biomaterials implanted into tissue will participate in the complex signalling
      between cells during wound healing. Recent studies have revealed that crucial
      cellular signalling pathways are regulated by the extra- and intracellular redox
      states and that reactive oxygen species function as intercellular signal
      molecules. Biomaterials have been shown to affect the respiratory burst response
      of surface-adhering leukocytes, thus interfering with major regulatory functions
      of cells also in surrounding tissues. The respiratory burst of surface-adhering
      leukocytes may thus be a key event in the understanding of biomaterial
      interaction with tissues, and the aim of this review is to highlight this field
      of research.

PMID- 11451656
TI  - Surface properties of Ascaris suum eggs: hydrophobic potential and Lewis acid
      base interactions.
AB  - The cell surface properties of Ascaris suum eggs were investigated to determine
      the hydrophobic properties of eggs of different origins. Hydrophobic potential
      measurements were based on adhesion to hydrocarbons. Freshly laid eggs with or
      without the external coat and eggs that had been stored for 3 months at -20
      degrees C were tested. The hydrophobic potential differed according to the
      hydrocarbon used (hexadecane or octane) and the eggs tested (stored or fresh).
      The hydrophobic potential with octane was 95% for fresh eggs and 72% for eggs
      stored at -20 degrees C. Tests with Ascaris eggs with and without an external
      coat showed similar hydrophobic characteristics; the presence or absence of this
      external structure did not appear to influence hydrophobic interactions. Acidic
      interactions also appeared to play no part in the adhesion of eggs to the surface
      of octane emulsions.

PMID- 11451657
TI  - Determination of surface free energy of interactive dry powder liposome
      formulations using capillary penetration technique.
AB  - The surface free energy of interactive dry powder formulations consisting of
      varying ratios of lactose plus liposomal ciprofloxacin were determined using
      capillary penetration technique. Powder is produced by jet-milling after mixing
      with lyophilized liposomal ciprofloxacin with inhalation grade lactose powder
      (Pharmatose 325M). Measurement of the weight gained during intrusion of different
      liquids in a packed column of powder is combined with dynamic considerations to
      give the surface free energy, gamma(sv). Confidence in methodology was gained by
      determining gamma(sv) for PMMA microspheres and comparing to literature values.
      Values of gamma(sv) are then obtained for unmilled Pharmatose 325M powder
      (gamma(sv)=54.2 mJ m(-2)), milled Pharmatose 325M (gamma(sv)=54.2 mJ m(-2)) and
      lipid:lactose formulations with weight ratios of 1:5, 1:10 and 1:20. All the
      powder liposomal formulations are found to have the same gamma(sv)=48.0 mJ m(-2),
      suggesting that adhesive forces in the three interactive powders should be
      similar barring any confounding roughness effects.

PMID- 11451658
TI  - The effect of alkyl core structure on micellar properties of poly(ethylene oxide)
      block-poly(L-aspartamide) derivatives.
AB  - Block copolymers based on fatty acid esters of poly(ethylene oxide)-block
      poly(hydroxy alkyl L-aspartamide) were prepared and characterized by 1H-NMR. The
      structure of the core-forming block was changed through application of different
      lengths of the poly(L-aspartamide) (PLAA) block, spacer group or fatty acid and
      varying the substitution level of the side chain on the polymeric backbone.
      Transmission electron microscopy and fluorescent probe studies provided evidence
      for the formation of supramolecular core/shell architectures with nanoscopic
      dimensions. The same techniques were used to study the effect of hydrophobic
      block structure on micellar size, critical micelle concentration (CMC), core
      polarity and viscosity of the polymeric micelles. Among the structural factors
      studied, it was revealed that the length of the PLAA block and the level of fatty
      acid attached to the polymeric backbone are the major factors affecting micellar
      properties. An increase in micellar size and reduction in CMC were observed when
      the level of fatty acid attachment to the polymeric backbone was raised. The
      elongation of the PLAA block, on the other hand, resulted in an increase in
      micellar size and core viscosity. Micellar size was the only characteristic being
      affected by the length of the attached fatty acid. However, a decrease in
      microviscosity was revealed when behenic acid (22 carbons) was attached to the
      core-forming block in a high level of substitution. The length of spacer group
      was also found to be a useful means by which the level of side chain attachment
      could be controlled. Chemical tailoring of the core structure in polymeric
      micelles may be used as an efficient means to change micellar properties. As a
      result, nanoscopic, spherical and stable micelles with improved core properties
      may be achieved to insure efficient loading and controlled release of an
      individual drug from the delivery system.

PMID- 11451659
TI  - Phagocytosis by Acanthamoeba castellanii: ionic strength dependence of the
      probability of cell attachment; ingestion and contact seam morphology.
AB  - The phagocytosis of glutaraldehyde-fixed horse erythrocytes by Acanthamoeba
      castellanii has been examined in iso-osmolal phosphate buffered saline/sucrose
      suspending phases of ionic strength, I, ranging from 0.17 to 0.0017. The
      erythrocytes were exposed, at a ratio of 15:1, to 5x10(6) amoeba in 0.2 ml
      volumes. The average number of erythrocytes forming a contact with an amoeba over
      30 min (T(30)) was well described by T(30)=5.2 exp(-0.112xI(-0.5)). The index of
      the exponential 'probability of attachment' term may also be expressed in terms
      of either surface potential (psi(0)) or the Debye length (kappa(-1)). The
      probability term is formally similar to a Bolzmann factor. Electron microscopy
      showed that contact spreading of the amoeba over the erythrocyte took place by
      formation of discrete contacts and that the lateral separation distance between
      contacts was 0.66, 1.36 and 1.59 &mgr;m for ionic strengths 0.17, 0.052 and
      0.0017, respectively. The direction of change in lateral contact separation
      distance was consistent with published changes in focal contact separation when
      amoeba move over glass or when human erythrocyte-erythrocyte adhesion occurs in
      different ionic strength media. The direction was also consistent with
      interfacial instability theory predictions for the dependence of localised
      membrane contact formation on interaction potential. The proportion of attached
      cells that were subsequently ingested correlated more strongly with the number of
      contacts formed along the cell-cell contact region (seam) than with the seam
      length at different ionic strengths.

PMID- 11451660
TI  - Interaction between erythrocytes from three different animals and emulsions
      prepared with various lecithins and oils.
AB  - The hemolysis of various animal erythrocytes in emulsions prepared with various
      emulsifying agents (lecithins) and oils was examined. In the emulsions stabilized
      with different emulsifying agents, the degree of hemolysis increased in the order
      soybean lecithin<egg yolk lecithin<hydrogenated egg yolk lecithin<hydrogenated
      soybean lecithin. In the emulsions stabilized with phospholipids with different
      iodine values that describe the degree of unsaturation in the fatty acyl groups
      of phospholipids, the percentage hemolysis decreased with increasing iodine
      value. In addition, in emulsions prepared with various triglycerides as the oil
      phase the percentage hemolysis increased with increasing triglyceride acyl chain
      length. The percentage hemolysis of the different animal erythrocytes increased
      in the order sheep<rabbit<guinea pig according to phosphatidylcholine contents in
      erythrocyte membrane of each animal. These results suggested that hemolysis
      caused by the interaction between erythrocytes and emulsions was involved in
      phospholipid dispersal such as liposome-like vesicles in the water phase, and was
      dependent on the phosphatidylcholine contents in both the emulsions and the
      erythrocyte membrane. Moreover, sphingomyelin in the erythrocyte membrane was
      found to be an important component for stabilization of erythrocyte membranes
      against hemolysis induced by intravenous fat or lipid emulsions.

PMID- 11451661
TI  - Soft particle analysis of bacterial cells and its interpretation of cell adhesion
      behaviors in terms of DLVO theory.
AB  - The electrokinetic properties of two nitrifying strains, Nitrosomonas europaea
      and Nitrobacter winogradskyi, and three heterotrophic bacteria, Escherichia coli,
      Pseudomonas putida and Pseudomonas aeruginosa, were examined by electrophoretic
      mobility measurement and analyzed using the soft particle electrophoresis theory
      that is suitable for biological particles. The bacterial adhesion characteristics
      onto glass bead substratum were also evaluated by packed bed method. The mobility
      of the bacterial cells employed converged to a non-zero value as the ionic
      concentration increased, suggesting that the bacterial cells exhibited typical
      soft particle characteristics. Moreover, cell surface potentials based on the
      soft particle theory were lower than those estimated by the conventional
      Smoluchowski formula, i.e. zeta potential. Cell collision efficiencies onto glass
      beads (alpha(0)) were largely dependent on interfacial interaction, although
      almost electrically neutral P. aeruginosa did not follow that trend. From a
      comparison of alpha(0) with DLVO interaction energy maximum (V(max)), it was
      assumed that heterocoagulation between cell and substratum at primary minimum
      potential took place under V(max) of 24-34 kT based on soft particle analysis. On
      the other hand, V(max) predictions using the Smoluchowski theory gave 81-223 kT,
      which indicated the possibility of overestimating electrostatic repulsive forces
      by the conventional Smoluchowski theory. Thus, the application of this new
      electrophoresis theory to several kinds of bacterial cells has led to the
      revision of the interpretation of bacterial mobility data and provided a more
      detailed understanding of the bacterial adhesion phenomenon.

PMID- 11451662
TI  - Comparison of adsorption behavior of two Mytilus edulis foot proteins on three
      surfaces.
AB  - The sea mussel Mytilus edulis fabricates a hold-fast (an adhesive plaque) from a
      proteinaceous mixture that it extrudes into a cavity formed by an organ called
      the 'foot'. A family of four proteins in the mixture known as M. edulis foot
      proteins (Mefp 1-4) have been purified to homogeneity. Mefp-1 and 2 are the most
      well-characterized and most easily purified members of the Mefp family. They
      constitute about 5 and 25% of the content of the plaque, respectively. It has
      been proposed that Mefp-1 mediates bonding to the intended substratum while Mefp
      2 serves more as a structural component. In order to provide data relevant to
      this hypothesis, the adsorption behavior of Mefp-1 and 2 was compared on three
      surfaces using attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR). Surfaces were germanium (Ge), polystyrene (PS) or
      poly(octadecyl)methacrylate (POMA). Polymer surfaces were prepared by spin
      casting onto the flat face of Ge trapezoidal internal reflection elements (IRE).
      Adsorption behavior was characterized by analyzing the kinetics of adsorption
      using a double exponential fit. The data indicate that the adsorption behavior of
      Mefp-1 and 2 is similar on the three surfaces both in terms of rate of adsorption
      and surface coverage attained over a short (<60 min) time period.

PMID- 11451663
TI  - Helical peptide models for protein glycation: proximity effects in catalysis of
      the Amadori rearrangement.
AB  - INTRODUCTION: Non-enzymatic glycation of proteins has been implicated in various
      diabetic complications and age-related disorders. Proteins undergo glycation at
      the N-terminus or at the epsilon-amino group of lysine residues. The observation
      that only a fraction of all lysine residues undergo glycation indicates the role
      of the immediate chemical environment in the glycation reaction. Here we have
      constructed helical peptide models, which juxtapose lysine with potentially
      catalytic residues in order to probe their roles in the individual steps of the
      glycation reaction. RESULTS: The peptides investigated in this study are
      constrained to adopt helical conformations allowing residues in the i and i+4
      positions to come into spatial proximity, while residues i and i+2 are far apart.
      The placing of aspartic acid and histidine residues at interacting positions with
      lysine modulates the steps involved in early peptide glycation (reversible Schiff
      base formation and its subsequent irreversible conversion to a ketoamine product,
      the Amadori rearrangement). Proximal positioning of aspartic acid or histidine
      with respect to the reactive lysine residue retards initial Schiff base
      formation. On the contrary, aspartic acid promotes catalysis of the Amadori
      rearrangement. Presence of the strongly basic residue arginine proximate to
      lysine favorably affects the pK(a) of both the lysine epsilon-amino group and the
      singly glycated lysine, aiding in the formation of doubly glycated species. The
      Amadori product also formed carboxymethyl lysine, an advanced glycation
      endproduct (AGE), in a time-dependent manner. CONCLUSIONS: Stereochemically
      defined peptide scaffolds are convenient tools for studying near neighbor effects
      on the reactivity of functional amino acid sidechains. The present study utilizes
      stereochemically defined peptide helices to effectively demonstrate that aspartic
      acid is an efficient catalytic residue in the Amadori arrangement. The results
      emphasize the structural determinants of Schiff base and Amadori product
      formation in the final accumulation of glycated peptides.

PMID- 11451664
TI  - Rapid screening of the aglycone specificity of glycosidases: applications to
      enzymatic synthesis of oligosaccharides.
AB  - BACKGROUND: Retaining glycosidases can catalyse glycosidic bond formation through
      transglycosylation from a donor sugar to an acceptor bound in the aglycone site.
      The aglycone specificity of a glycosidase is not easily determined, thereby
      complicating the choice of the most appropriate glycosidase for use as a catalyst
      for transglycosylation. We have developed a strategy to rapidly screen the
      aglycone specificity of a glycosidase and thereby determine which enzymes are
      best suited to catalyse specific transglycosylation reactions. RESULTS: The
      reactivation, or turnover, of a glycosidase trapped as a fluoroglycosyl-enzyme
      species is accelerated in the presence of a compound that productively binds to
      the aglycone site. This methodology was used to rapidly screen six glycosidases
      with 44 potential acceptor sugars. Validation of the screening strategy was
      demonstrated by the identification of products formed from a transglycosylation
      reaction with positively screened acceptors for four of the enzymes studied.
      CONCLUSIONS: The aglycone specificity of a glycosidase can be rapidly evaluated
      and requires only an appropriate fluorosugar inactivator, a substrate for assay
      of activity and a library of compounds for screening.

PMID- 11451665
TI  - Engineered biosynthesis of novel polyenes: a pimaricin derivative produced by
      targeted gene disruption in Streptomyces natalensis.
AB  - BACKGROUND: The post-polyketide synthase biosynthetic tailoring of polyene
      macrolides usually involves oxidations catalysed by cytochrome P450
      monooxygenases (P450s). Although members from this class of enzymes are common in
      macrolide biosynthetic gene clusters, their specificities vary considerably
      toward the substrates utilised and the positions of the hydroxyl functions
      introduced. In addition, some of them may yield epoxide groups. Therefore, the
      identification of novel macrolide monooxygenases with activities toward
      alternative substrates, particularly epoxidases, is a fundamental aspect of the
      growing field of combinatorial biosynthesis. The specific alteration of these
      activities should constitute a further source of novel analogues. We investigated
      this possibility by directed inactivation of one of the P450s belonging to the
      biosynthetic gene cluster of an archetype polyene, pimaricin. RESULTS: A
      recombinant mutant of the pimaricin-producing actinomycete Streptomyces
      natalensis produced a novel pimaricin derivative, 4,5-deepoxypimaricin, as a
      major product. This biologically active product resulted from the phage-mediated
      targeted disruption of the gene pimD, which encodes the cytochrome P450 epoxidase
      that converts deepoxypimaricin into pimaricin. The 4,5-deepoxypimaricin has been
      identified by mass spectrometry and nuclear magnetic resonance following high
      performance liquid chromatography purification. CONCLUSIONS: We have demonstrated
      that PimD is the epoxidase responsible for the conversion of 4,5-deepoxypimaricin
      to pimaricin in S. natalensis. The metabolite accumulated by the recombinant
      mutant, in which the epoxidase has been knocked out, constitutes the first
      designer polyene obtained by targeted manipulation of a polyene biosynthetic gene
      cluster. This novel epoxidase could prove to be valuable for the introduction of
      epoxy substituents into designer macrolides.

PMID- 11451666
TI  - RFI-641 inhibits entry of respiratory syncytial virus via interactions with
      fusion protein.
AB  - BACKGROUND: RFI-641, a small dendrimer-like compound, is a potent and selective
      inhibitor of respiratory syncytial virus (RSV), which is currently a clinical
      candidate for the treatment of upper and lower respiratory tract infections
      caused by RSV. RFI-641 inhibits RSV growth with an IC(50) value of 50 nM and
      prevents syncytia formation in tissue culture. RSV contains of three surface
      glycoproteins, a small hydrophobic (SH) protein of unknown function, and
      attachment (G) and fusion (F) proteins that enable binding and fusion of virus,
      respectively, with target cells. Because of their role in attachment and fusion,
      the G and F surface proteins are prominent targets for therapeutic intervention.
      RFI-641 was previously shown to bind purified preparations of RSV fusion protein.
      Based on this observation, in conjunction with the biological results, it was
      speculated that the fusion event might be the target of these inhibitors.
      RESULTS: A fusion assay based upon the relief of self-quenching of octadecyl
      rhodamine R18 was used to determine effects of the inhibitors on binding and
      fusion of RSV. The results show that RFI-641 inhibits both RSV-cell binding and
      fusion events. The inhibition of RSV is mediated via binding to the fusion
      protein on the viral surface. A closely related analog, WAY-158830, which is much
      less active in the virus-infectivity assay does not inhibit binding and fusion of
      RSV with Vero cells. CONCLUSIONS: RFI-641, an in vivo active RSV inhibitor, is
      shown to inhibit both binding and fusion of RSV with cells, events that are early
      committed steps in RSV entry and pathogenicity. The results described here
      demonstrate that a non-peptidic, small molecule can inhibit binding and fusion of
      enveloped virus specifically via interaction with the viral fusion protein.

PMID- 11451667
TI  - Filamentous bacteriophage stability in non-aqueous media.
AB  - BACKGROUND: Filamentous bacteriophage are used as general cloning vectors as well
      as phage display vectors in order to study ligand-receptor interactions. Exposure
      to biphasic chloroform-water interface leads to specific contraction of phage, to
      non-infective I- or S-forms. RESULTS: Upon exposure, phage were inactivated (non
      infective) at methanol, ethanol and 1-propanol concentrations inversely dependent
      upon alcohol hydrophobicity. Infectivity loss of phage at certain concentrations
      of 1-propanol or ethanol coincided with changes in the spectral properties of the
      f1 virion in ultraviolet fluorescence and circular dichroism studies.
      CONCLUSIONS: The alcohols inactivate filamentous phage by a general mechanism-
      solvation of coat protein--thereby disrupting the capsid in a manner quite
      different from the previously reported I- and S-forms. The infectivity retention
      of phagemid pG8H6 in 99% acetonitrile and the relatively high general solvent
      resistance of the phage strains studied here open up the possibility of employing
      phage display in non-aqueous media.

PMID- 11451668
TI  - Covalent capture: a new tool for the purification of synthetic and recombinant
      polypeptides.
AB  - BACKGROUND: Purification of polypeptides and proteins derived from recombinant
      DNA techniques and of long synthetic polypeptides often represents a challenge.
      Affinity methods exist, but generally require addition of a large recognition
      unit to the target protein and use of expensive purification media. Use of large
      units is dictated by the characteristics of non-covalent complexes, where the
      energy necessary to form the complex derives from the sum of multiple weak energy
      interactions. Covalent interactions in contrast are of high energy, even when
      only a few bonds are formed. We decided to explore the use of the reversible
      covalent bond formed between N-terminal cysteine and threonine residues with an
      aldehyde as a method of protein purification. RESULTS: A series of test peptides
      with N-terminal cysteine and threonine were captured by a polyethyleneglycol
      polyacrylamide resin to which an aldehyde function had been grafted. Peptides
      with other amino acids at the N-terminus did not interact with the resin. A
      recombinant polypeptide with N-terminal cysteine was purified to 90% purity in
      one step. Polypeptides were eluted from the resin simply by adding a
      hydroxylamine derivative, which reacts with aldehyde functions to form an oxime.
      CONCLUSIONS: Polypeptides possessing N-terminal cysteine or threonine can be
      easily purified using this 'covalent capture' approach.

PMID- 11451669
TI  - Insights about the biosynthesis of the avermectin deoxysugar L-oleandrose through
      heterologous expression of Streptomyces avermitilis deoxysugar genes in
      Streptomyces lividans.
AB  - BACKGROUND: The avermectins, produced by Streptomyces avermitilis, are potent
      anthelminthic agents with a polyketide-derived macrolide skeleton linked to a
      disaccharide composed of two alpha-linked L-oleandrose units. Eight contiguous
      genes, avrBCDEFGHI (also called aveBI-BVIII), are located within the avermectin
      producing gene cluster and have previously been mapped to the biosynthesis and
      attachment of thymidinediphospho-oleandrose to the avermectin aglycone. This gene
      cassette provides a convenient way to study the biosynthesis of 2,6
      dideoxysugars, namely that of L-oleandrose, and to explore ways to alter the
      biosynthesis and structures of the avermectins by combinatorial biosynthesis.
      RESULTS: A Streptomyces lividans strain harboring a single plasmid with the
      avrBCDEFGHI genes in which avrBEDC and avrIHGF were expressed under control of
      the actI and actIII promoters, respectively, correctly glycosylated exogenous
      avermectin A1a aglycone with identical oleandrose units to yield avermectin A1a.
      Modified versions of this minimal gene set produced novel mono- and disaccharide
      avermectins. The results provide further insight into the biosynthesis of L
      oleandrose. CONCLUSIONS: The plasmid-based reconstruction of the avr deoxysugar
      genes for expression in a heterologous system combined with biotransformation has
      led to new information about the mechanism of 2,6-deoxysugar biosynthesis. The
      structures of the di-demethyldeoxysugar avermectins accumulated indicate that in
      the oleandrose pathway the stereochemistry at C-3 is ultimately determined by the
      3-O-methyltransferase and not by the 3-ketoreductase or a possible 3,5-epimerase.
      The AvrF protein is therefore a 5-epimerase and not a 3,5-epimerase. The ability
      of the AvrB (mono-)glycosyltransferase to accommodate different deoxysugar
      intermediates is evident from the structures of the novel avermectins produced.

PMID- 11451670
TI  - Hexosaminidase inhibitors as new drug candidates for the therapy of
      osteoarthritis.
AB  - BACKGROUND: Articular cartilage from patients with osteoarthritis is
      characterized by a decreased concentration and reduced size of
      glycosaminoglycans. Degeneration of the cartilage matrix is a multifactorial
      process, which is due in part to accelerated glycosaminoglycan catabolism.
      Recently, we have demonstrated that hexosaminidase represents the dominant
      glycosaminoglycan-degrading glycosidase released by chondrocytes into the
      extracellular compartment and is the dominant glycosidase in synovial fluid from
      patients with osteoarthritis. Inhibition of hexosaminidase activity may represent
      a novel approach to the prevention of cartilage matrix glycosaminoglycan
      degradation and a potentially new strategy to treat osteoarthritis. RESULTS: We
      have synthesized and investigated a series of iminocyclitols designed as
      transition-state analog inhibitors of human hexosaminidase, and demonstrated that
      the five-membered iminocyclitol 4 expresses the strongest inhibitory activity
      with K(i)=24 nM. Inhibition of hexosaminidase activity in human cultured
      articular chondrocytes and human chondrosarcoma cells with iminocyclitol 4
      resulted in accumulation of hyaluronic acid and sulfated glycosaminoglycans in
      the cell-associated fraction. Similarly, incubation of human cartilage tissue
      with iminocyclitol 4 resulted in an accumulation of glycosaminoglycans in the
      pericellular compartment. CONCLUSIONS: Inhibition of hexosaminidase activity
      represents a new strategy for preventing or even reversing cartilage degradation
      in patients with osteoarthritis.

PMID- 11451671
TI  - Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of
      polyketide synthase and late genes.
AB  - BACKGROUND: The polyene macrolide amphotericin B is produced by Streptomyces
      nodosus ATCC14899. Amphotericin B is a potent antifungal antibiotic and has
      activity against some viruses, protozoans and prions. Treatment of systemic
      fungal infections with amphotericin B is complicated by its low water-solubility
      and side effects which include severe nephrotoxicity. Analogues with improved
      properties could be generated by manipulating amphotericin biosynthetic genes in
      S. nodosus. RESULTS: A large polyketide synthase gene cluster was cloned from
      total cellular DNA of S. nodosus. Nucleotide sequence analysis of 113193 bp of
      this region revealed six large polyketide synthase genes as well as genes for two
      cytochrome P450 enzymes, two ABC transporter proteins, and genes involved in
      biosynthesis and attachment of mycosamine. Phage KC515-mediated gene disruption
      was used to show that this region is involved in amphotericin production.
      CONCLUSIONS: The availability of these genes and the development of a method for
      gene disruption and replacement in S. nodosus should allow production of novel
      amphotericins. A panel of analogues could lead to identification of derivatives
      with increased solubility, improved biological activity and reduced toxicity.

PMID- 11451672
TI  - Cloning and characterization of a phosphopantetheinyl transferase from
      Streptomyces verticillus ATCC15003, the producer of the hybrid peptide-polyketide
      antitumor drug bleomycin.
AB  - BACKGROUND: Phosphopantetheinyl transferases (PPTases) catalyze the
      posttranslational modification of carrier proteins by the covalent attachment of
      the 4'-phosphopantetheine (P-pant) moiety of coenzyme A to a conserved serine
      residue, a reaction absolutely required for the biosynthesis of natural products
      including fatty acids, polyketides, and nonribosomal peptides. PPTases have been
      classified according to their carrier protein specificity. In organisms
      containing multiple P-pant-requiring pathways, each pathway has been suggested to
      have its own PPTase activity. However, sequence analysis of the bleomycin
      biosynthetic gene cluster in Streptomyces verticillus ATCC15003 failed to reveal
      an associated PPTase gene. RESULTS: A general approach for cloning PPTase genes
      by PCR was developed and applied to the cloning of the svp gene from S.
      verticillus. The svp gene is mapped to an independent locus not clustered with
      any of the known NRPS or PKS clusters. The Svp protein was overproduced in
      Escherichia coli, purified to homogeneity, and shown to be a monomer in solution.
      Svp is a PPTase capable of modifying both type I and type II acyl carrier
      proteins (ACPs) and peptidyl carrier proteins (PCPs) from either S. verticillus
      or other Streptomyces species. As compared to Sfp, the only 'promiscuous' PPTase
      known previously, Svp displays a similar catalytic efficiency (k(cat)/K(m)) for
      the BlmI PCP but a 346-fold increase in catalytic efficiency for the TcmM ACP.
      CONCLUSIONS: PPTases have recently been re-classified on a structural basis into
      two subfamilies: ACPS-type and Sfp-type. The development of a PCR method for
      cloning Sfp-type PPTases from actinomycetes, the recognition of the Sfp-type
      PPTases to be associated with secondary metabolism with a relaxed carrier protein
      specificity, and the availability of Svp, in addition to Sfp, should facilitate
      future endeavors in engineered biosynthesis of peptide, polyketide, and, in
      particular, hybrid peptide-polyketide natural products.

PMID- 11451674
TI  - Growth and development of tetracycline-resistant Chlamydia suis.
AB  - Tetracycline (TET) is a front-line antibiotic for the treatment of chlamydial
      infections in both humans and animals, and the emergence of TET-resistant
      (Tet(r)) Chlamydia is of significant clinical importance. Recently, several
      Tet(r) chlamydial strains have been isolated from swine (Sus scrofa) raised in
      production facilities in Nebraska. Here, the intracellular development of two
      Tet(r) strains, R19 and R27, is characterized through the use of tissue culture
      and immunofluorescence. The strains grow in concentrations of up to 4 microg of
      TET/ml, while a TET-sensitive (Tet(s)) swine strain (S45) and a strain of the
      human serovar L2 (LGV-434) grow in up to 0.1 microg of TET/ml. Although
      inclusions form in the presence of TET, many contain large aberrant reticulate
      bodies (RBs) that do not differentiate into infectious elementary bodies. The
      percentage of inclusions containing typical developmental forms decreases with
      increasing TET concentrations, and at 3 microg of TET/ml 100% of inclusions
      contain aberrant RBs. However, upon removal of TET the aberrant RBs revert to
      typical RBs, and a productive developmental cycle ensues. In addition, inclusions
      were found that contained both C. suis R19 and Chlamydia trachomatis L2 after
      sequential infection, demonstrating that two biologically distinct chlamydial
      strains could both develop within a single inclusion.

PMID- 11451673
TI  - Clinical and experimental advances in treatment of visceral leishmaniasis.

PMID- 11451675
TI  - In vitro activity of gemifloxacin (SB-265805, LB20304a) against Legionella
      pneumophila and its pharmacokinetics in guinea pigs with L. pneumophila
      pneumonia.
AB  - The activity of gemifloxacin against intracellular Legionella pneumophila and for
      the treatment of guinea pigs with L. pneumophila pneumonia was studied.
      Gemifloxacin, azithromycin, and levofloxacin (1 microg/ml) reduced bacterial
      counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by
      2 to 3 log(10) units. Gemifloxacin and levofloxacin had roughly equivalent
      intracellular activities. In contrast, erythromycin had static activity only.
      Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in
      guinea pigs with L. pneumophila pneumonia. When gemifloxacin (10 mg/kg) was given
      by the intraperitoneal (i.p.) route to infected guinea pigs, mean peak levels in
      plasma were 1.3 microg/ml at 0.5 h and 1.2 microg/ml at 1 h postinjection. The
      terminal half-life phase of elimination from plasma was 1.3 h, and the area under
      the concentration-time curve from 0 to 24 h (AUC(0--24)) was 2.1 microg. h/ml.
      For the same drug dose, mean levels in lungs were 3.4 microg/g at both 0.5 and 1
      h, with a half-life of 1.5 h and an AUC(0--24) of 6.0 microg. h/ml. All 15 L.
      pneumophila-infected guinea pigs treated with gemifloxacin (10 mg/kg/dose given
      i.p. once daily) for 2 days survived for 9 days after antimicrobial therapy, as
      did 13 of 14 guinea pigs treated with the same dose of gemifloxacin given for 5
      days. All 12 azithromycin-treated animals (15 mg/kg/dose given i.p. once daily
      for 2 days) survived, as did 11 of 12 animals treated with levofloxacin (10
      mg/kg/dose given i.p. once daily for 5 days). None of 12 animals treated with
      saline survived. Gemifloxacin is effective against L. pneumophila in infected
      macrophages and in a guinea pig model of Legionnaires' disease, even with an
      abbreviated course of therapy. These data support studies of the clinical
      effectiveness of gemifloxacin for the treatment of Legionnaires' disease.

PMID- 11451676
TI  - Telithromycin is active against Mycobacterium avium in mice despite lacking
      significant activity in standard in vitro and macrophage assays and is associated
      with low frequency of resistance during treatment.
AB  - The activity of telithromycin, a new ketolide, was evaluated in vitro and in vivo
      against Mycobacterium avium complex (MAC) strains. The MIC of telithromycin for
      several M. avium isolates obtained from the blood of AIDS patients ranged from 16
      to >128 microg/ml (MIC at which 90% of isolates are inhibited, >128 microg/ml),
      and the compound did show activity in the macrophage system at concentrations
      greater than 8 or 16 microg/ml, but this was dependent on the MAC strain used.
      Telithromycin was then administered to mice infected with MAC strain 101 for 4
      weeks at doses of 100, 200, or 400 mg/kg of body weight/day. Treatment with 100
      and 200 mg/kg/day was bacteriostatic, but at 400 mg/kg/day telithromycin was
      bactericidal for MAC strains. The frequency of the emergence of resistance to
      telithromycin was low despite prolonged usage (12 weeks). This study demonstrates
      that telithromycin is active in vivo against MAC and warrants further evaluation.

PMID- 11451677
TI  - Kinetic study of two novel enantiomeric tricyclic beta-lactams which efficiently
      inactivate class C beta-lactamases.
AB  - A detailed kinetic study of the interaction between two ethylidene derivatives of
      tricyclic carbapenems, Lek 156 and Lek 157, and representative beta-lactamases
      and D-alanyl-D-alanine peptidases (DD-peptidases) is presented. Both compounds
      are very efficient inactivators of the Enterobacter cloacae 908R beta-lactamase,
      which is usually resistant to inhibition. Preliminary experiments indicate that
      various extended-spectrum class C beta-lactamases (ACT-1, CMY-1, and MIR-1) are
      also inactivated. With the E. cloacae 908R enzyme, complete inactivation occurs
      with a second-order rate constant, k(2)/K', of 2 x 10(4) to 4 x 10(4) M(-1) s(
      1), and reactivation is very slow, with a half-life of >1 h. Accordingly, Lek 157
      significantly decreases the MIC of ampicillin for E. cloacae P99, a constitutive
      class C beta-lactamase overproducer. With the other serine beta-lactamases
      tested, the covalent adducts exhibit a wide range of stabilities, with half-lives
      ranging from long (>4 h with the TEM-1 class A enzyme), to medium (10 to 20 min
      with the OXA-10 class D enzyme), to short (0.2 to 0.4 s with the NmcA class A
      beta-lactamase). By contrast, both carbapenems behave as good substrates of the
      Bacillus cereus metallo-beta-lactamase (class B). The Streptomyces sp. strain R61
      and K15 extracellular DD-peptidases exhibit low levels of sensitivity to both
      compounds.

PMID- 11451678
TI  - Metallo-beta-lactamases in clinical Pseudomonas isolates in Taiwan and
      identification of VIM-3, a novel variant of the VIM-2 enzyme.
AB  - A total of 209 clinical isolates of Pseudomonas (193 Pseudomonas aeruginosa, 10
      P. putida, 4 P. stutzeri, and 2 P. fluorescens isolates) with reduced
      susceptibilities to imipenem and/or ceftazidime were subjected to PCR assays with
      primers specific for bla(IMP-1), bla(IMP-2), bla(VIM-1), and bla(VIM-2) and
      sequence analysis to identify the metallo-beta-lactamases (MBLs) prevalent among
      these organisms in Taiwan; and 21 isolates gave positive results. Five isolates
      including two P. putida and three P. stutzeri isolates were found to carry
      bla(IMP-1), and six isolates including five P. putida and one P. stutzeri
      isolates harbored bla(VIM-2). The remaining 10 isolates were P. aeruginosa, and
      all were found to carry a novel variant of bla(VIM-2), designated bla(VIM-3).
      There are only two nucleotide differences between bla(VIM-2) and bla(VIM-3),
      leading to two amino acid alterations. Our findings indicate that VIM-2 and its
      variant have become the most prevalent metalloenzymes in Pseudomonas in Taiwan.
      Southern hybridization with the bla(VIM-2)-, bla(VIM-3)-, and bla(IMP-1 )
      specific probes revealed that only two VIM-2-producing P. putida isolates
      appeared to carry the MBL gene on plasmids. Pulsed-field gel electrophoresis
      showed that six VIM-3-producing P. aeruginosa isolates and two IMP-1-producing P.
      stutzeri isolates were genetically related, suggesting that the spread of these
      MBL genes in Taiwan could be due to clonal dissemination as well as genetic
      exchange between different clones.

PMID- 11451679
TI  - Sodium lauryl sulfate abrogates human immunodeficiency virus infectivity by
      affecting viral attachment.
AB  - The microbicidal activity of sodium lauryl sulfate (SLS) against human
      immunodeficiency virus type 1 (HIV-1) was studied in cultured cells. Pretreatment
      of HIV-1(NL4-3) with SLS decreased, in a concentration-dependent manner, its
      infectivity when using 1G5 as target cells. In the absence of a viral
      pretreatment period or when 1G5 cells were pretreated with SLS, the surfactant
      induced inactivation of viral infectivity was less pronounced, especially at
      concentrations between 375 and 550 microM. SLS had no effect on HIV-1 when the
      virus was adsorbed to 1G5 cells by a 2-h incubation period. SLS almost completely
      inhibited the fusion process by decreasing the attachment of HIV-1 to target
      cells. SLS also inhibited the infectivity of HIV-1-based luciferase reporter
      viruses pseudotyped with the amphotropic murine leukemia virus envelope (which
      enters cells in a CD4-, CCR5-, and CXCR4-independent manner), indicating that SLS
      may inactivate other envelope viruses. In contrast, no effect was seen with
      vesicular stomatitis virus envelope glycoprotein G (which enters cells through
      receptor-mediated endocytosis) pretreated with up to 700 microM SLS. SLS also
      decreased, in a dose-dependent manner, the HIV-1-dependent syncytium formation
      between 1G5 and J1.1 cells after a 24-h incubation. The reduction of luciferase
      activity was more pronounced when J1.1 cells (which express HIV-1 proteins on
      their surface) were pretreated with SLS rather than 1G5 cells. Taken together,
      our results suggest that SLS could represent a candidate of choice for use in
      vaginal microbicides to prevent the sexual transmission of HIV and possibly other
      pathogens causing sexually transmitted diseases.

PMID- 11451680
TI  - Overexpression and characterization of the chromosomal aminoglycoside 2'-N
      acetyltransferase of Providencia stuartii.
AB  - The gene coding for aminoglycoside 2'-N-acetyltransferase Ia [AAC(2')-Ia] from
      Providencia stuartii was amplified by PCR and cloned. The resulting construct,
      pACKF2, was transferred into Escherichia coli for overexpression of AAC(2')-Ia as
      a fusion protein with an N-terminal hexa-His tag. The fusion protein was isolated
      and purified by affinity chromatography on Ni(2+)-nitrilotriacetic acid agarose
      and gel permeation chromatography on Superdex 75. Comparison of the specific
      activity of this enzyme with that of its enterokinase-digested derivative lacking
      the His tag indicated that the presence of the extra N-terminal peptide does not
      affect activity. The temperature and pH optima for activity of both forms of the
      2'-N-acetyltransferase were 20 degrees C and pH 6.0, respectively, while the
      enzymes were most stable at 15 degrees C and pH 8.1. The Michaelis-Menten kinetic
      parameters for AAC(2')-Ia at 20 degrees C and pH 6.0 were determined using a
      series of aminoglycoside antibiotics possessing a 2'-amino group and a
      concentration of acetyl coenzyme A fixed at 10 times its K(m) value of 8.75
      microM. Under these conditions, gentamicin was determined to be the best
      substrate for the enzyme in terms of both K(m) and k(cat)/K(m) values, whereas
      neomycin was the poorest. Comparison of the kinetic parameters obtained with the
      different aminoglycosides indicated that their hexopyranosyl residues provided
      the most important binding sites for AAC(2')-Ia activity, while the enzyme
      exhibits greater tolerance further from these sites. No correlation was found
      between these kinetic parameters and MICs determined for P. stuartii PR50
      expressing the 2'-N-acetyltransferase, suggesting that its true in vivo function
      is not as a resistance factor.

PMID- 11451681
TI  - Natural antibiotic susceptibilities of Edwardsiella tarda, E. ictaluri, and E.
      hoshinae.
AB  - The natural antibiotic susceptibilities to 71 antibiotics of 102 Edwardsiella
      strains belonging to E. tarda (n = 42), E. ictaluri (n = 41), and E. hoshinae (n
      = 19) were investigated. MICs were determined using a microdilution procedure
      according to NCCLS criteria and German standards. All edwardsiellae were
      naturally sensitive to tetracyclines, aminoglycosides, most beta-lactams,
      quinolones, antifolates, chloramphenicol, nitrofurantoin, and fosfomycin.
      Edwardsiella species were naturally resistant to macrolides, lincosamides,
      streptogramins, glycopeptides, rifampin, fusidic acid, and oxacillin. Although
      slight species-dependent differences in natural susceptibilities to some
      antibiotics (e.g., macrolides and cefaclor) were seen, differences in natural
      susceptibility affecting clinical assessment criteria were only seen with
      benzylpenicillin. Whereas E. tarda was naturally resistant to benzylpenicillin,
      E. hoshinae was naturally sensitive. Natural sensitivity and resistance to this
      penicillin were found among the strains of E. ictaluri. The observed oxacillin
      sensitivity of E. ictaluri was attributed to the failure of the species to grow
      at higher salt concentrations found in oxacillin-containing microtiter plates.
      The present study describes a database concerning the natural susceptibility of
      Edwardsiella species to a wide range of antibiotics, which can be applied to
      validate forthcoming antibiotic susceptibility tests of these microorganisms.

PMID- 11451682
TI  - Echinococcus multilocularis alkaline phosphatase as a marker for metacestode
      damage induced by in vitro drug treatment with albendazole sulfoxide and
      albendazole sulfone.
AB  - Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox
      tapeworm Echinococcus multilocularis. The disease affects the human liver and
      occasionally other organs and is fatal if treatment is unsuccessful. The present
      chemotherapy of AE is based on the administration of benzimidazole carbamate
      derivatives, such as mebendazole and albendazole. Albendazole treatment has been
      found to be ineffective in some cases, parasitostatic rather than parasiticidal,
      and the recurrence rate is rather high. Therefore, chemotherapy usually involves
      the lifelong uptake of massive doses of albendazole and new treatment options are
      urgently needed. In order to avoid costly and time-consuming animal
      experimentation, a first step in searching for novel parasiticidal compounds
      could be the in vitro drug screening of novel compounds by employing metacestode
      cultivation. However, presently used techniques (e.g., transmission electron
      microscopy) for determination of parasite viability involve costly equipment and
      time-consuming preparation of rather large amounts of parasite material. We
      therefore searched for a parasite marker which can be easily traced and the
      presence or absence of which is indicative of parasite viability. In this study
      we show that the increase of E. multilocularis alkaline phosphatase activity in
      culture supernatants during in vitro drug treatment with albendazole derivatives
      correlates with the progressive degeneration and destruction of the metacestode
      tissue. The inexpensive and rapid assay presented here will serve as an ideal
      tool for performing first-round in vitro tests on the efficacy of a large number
      of antiparasitic compounds.

PMID- 11451683
TI  - Type II topoisomerase mutations in fluoroquinolone-resistant clinical strains of
      Pseudomonas aeruginosa isolated in 1998 and 1999: role of target enzyme in
      mechanism of fluoroquinolone resistance.
AB  - The major mechanism of resistance to fluoroquinolones for Pseudomonas aeruginosa
      is the modification of type II topoisomerases (DNA gyrase and topoisomerase IV).
      We examined the mutations in quinolone-resistance-determining regions (QRDR) of
      gyrA, gyrB, parC, and parE genes of recent clinical isolates. There were 150
      isolates with reduced susceptibilities to levofloxacin and 127 with reduced
      susceptibilities to ciprofloxacin among 513 isolates collected during 1998 and
      1999 in Japan. Sequencing results predicted replacement of an amino acid in the
      QRDR of DNA gyrase (GyrA or GyrB) for 124 of the 150 strains (82.7%); among
      these, 89 isolates possessed mutations in parC or parE which lead to amino acid
      changes. Substitutions of both Ile for Thr-83 in GyrA and Leu for Ser-87 in ParC
      were the principal changes, being detected in 48 strains. These replacements were
      obviously associated with reduced susceptibilities to levofloxacin,
      ciprofloxacin, and sparfloxacin; however, sitafloxacin showed high activity
      against isolates with these replacements. We purified GyrA (The-83 to Ile) and
      ParC (Ser-87 to Leu) by site-directed mutagenesis and compared the inhibitory
      activities of the fluoroquinolones. Sitafloxacin showed the most potent
      inhibitory activities against both altered topoisomerases among the
      fluoroquinolones tested. These results indicated that, compared with other
      available quinolones, sitafloxacin maintained higher activity against recent
      clinical isolates with multiple mutations in gyrA and parC, which can be
      explained by the high inhibitory activities of sitafloxacin against both mutated
      enzymes.

PMID- 11451684
TI  - Novel cefotaximase (CTX-M-16) with increased catalytic efficiency due to
      substitution Asp-240-->Gly.
AB  - Three clinical strains (Escherichia coli Rio-6, E. coli Rio-7, and Enterobacter
      cloacae Rio-9) collected in 1996 and 1999 from hospitals in Rio de Janeiro
      (Brazil) were resistant to broad-spectrum cephalosporins and gave a positive
      double-disk synergy test. Two bla(CTX-M) genes encoding beta-lactamases of pl 7.9
      and 8.2 were implicated in this resistance: the bla(CTX-M-9) gene observed in E.
      coli Rio-7 and E. cloacae Rio-9 and a novel CTX-M-encoding gene, designated
      bla(CTX-M-16), observed in E. coli strain Rio-6. The deduced amino acid sequence
      of CTX-M-16 differed from CTX-M-9 only by the substitution Asp-240-->Gly. The CTX
      M-16-producing E. coli transformant exhibited the same level of resistance to
      cefotaxime (MIC, 16 microg/ml) but had a higher MIC of ceftazidime (MIC, 8 versus
      1 microg/ml) than the CTX-M-9-producing transformant. Enzymatic studies revealed
      that CTX-M-16 had a 13-fold higher affinity for aztreonam and a 7.5-fold higher
      k(cat) for ceftazidime than CTX-M-9, thereby showing that the residue in position
      240 can modulate the enzymatic properties of CTX-M enzymes. The two bla(CTX-M-9)
      genes and the bla(CTX-M-16) gene were located on different plasmids, suggesting
      the presence of mobile elements associated with CTX-M-encoding genes. CTX-M-2 and
      CTX-M-8 enzymes were found in Brazil in 1996, and two other CTX-M beta
      lactamases, CTX-M-9 and CTX-M-16, were subsequently observed. These reports are
      evidence of the diversity of CTX-M-type extended-spectrum beta-lactamases in
      Brazil.

PMID- 11451685
TI  - Variants other than aspartic acid at codon 69 of the human immunodeficiency virus
      type 1 reverse transcriptase gene affect susceptibility to nuleoside analogs.
AB  - The T69D mutation in the human immunodeficiency virus type 1 reverse
      transcriptase (RT) gene has been associated with reduced susceptibility to
      dideoxycytosine (ddC); however, several other mutations at codon 69 have been
      observed in antiretroviral drug-treated patients. The Stanford HIV RT and
      Protease Sequence Database was interrogated and showed that 23% of patients
      treated with nucleoside RT inhibitors (NRTI) had mutations at codon 69. These
      variants included T69N, -S, -A, -G, -E, -I, and -K mutations that were present in
      patients treated with NRTI but not in drug-naive patients. Treatment history
      information showed that a substantial percentage of these codon 69 changes
      occurred in patients administered non-ddC-containing regimens. Different and
      specific patterns of other RT gene mutations were associated with the various
      codon 69 mutations. Drug susceptibility assays showed that viral constructs
      containing codon 69 variants could have reduced susceptibility to ddC and other
      RT inhibitors. These results suggest that the T69D mutation is not the only codon
      69 variant associated with drug resistance and that ddC is not the only drug
      affected.

PMID- 11451686
TI  - Macrolide resistance gene mreA of Streptococcus agalactiae encodes a flavokinase.
AB  - The mreA gene from Streptococcus agalactiae COH31 gamma/delta, resistant to
      macrolides and clindamycin by active efflux, has recently been cloned in
      Escherichia coli, where it was reported to confer macrolide resistance (J.
      Clancy, F. Dib-Hajj, J. W. Petitpas, and W. Yuan, Antimicrob. Agents Chemother.
      41:2719--2723, 1997). Cumulative data suggested that the mreA gene was located on
      the chromosome of S. agalactiae COH31 gamma/delta. Analysis of the deduced amino
      acid sequence of mreA revealed significant homology with several bifunctional
      flavokinases/(flavin adenine dinucleotide (FAD) synthetases, which convert
      riboflavin to flavin mononucleotide (FMN) and FMN to FAD, respectively. High
      performance liquid chromatography experiments showed that the mreA gene product
      had a monofunctional flavokinase activity, similar to that of RibR from Bacillus
      subtilis. Sequences identical to those of the mreA gene and of a 121-bp upstream
      region containing a putative promoter were detected in strains of S. agalactiae
      UCN4, UCN5, and UCN6 susceptible to macrolides. mreA and its allele from S.
      agalactiae UCN4 were cloned on the shuttle vector pAT28. Both constructs were
      introduced into E. coli, where they conferred a similar two- to fourfold increase
      in the MICs of erythromycin, spiramycin, and clindamycin. The MICs of a variety
      of other molecules, including crystal violet, acriflavin, sodium dodecyl sulfate,
      and antibiotics, such as certain cephalosporins, chloramphenicol, doxycycline,
      nalidixic acid, novobiocin, and rifampin, were also increased. In contrast,
      resistance to these compounds was not detected when the constructs were
      introduced into E. faecalis JH2-2. In conclusion, the mreA gene was probably
      resident in S. agalactiae and may encode a metabolic function. We could not
      provide any evidence that it was responsible for macrolide resistance in S.
      agalactiae COH31 gamma/delta; broad-spectrum resistance conferred by the gene in
      E. coli could involve multidrug efflux pumps by a mechanism that remains to be
      elucidated.

PMID- 11451688
TI  - Large drug resistance virulence plasmids of clinical isolates of Salmonella
      enterica serovar Choleraesuis.
AB  - Salmonella enterica serovar Choleraesuis generally causes systemic human
      salmonellosis without diarrhea, and therefore, antimicrobial treatment is
      essential for such patients. The drug resistance information on this organism is
      thus of high value. Serovar Choleraesuis usually harbors a virulence plasmid
      (pSCV) of 50 kb in size. Of the 16 clinical isolates identified to be serovar
      Choleraesuis, all except one harbored a pSCV and seven of them carried a pSCV of
      more than 125 kb in size. A pSCV was defined as a plasmid carrying spvC and
      characteristic deletions detected by PCR and by DNA-DNA hybridization (for the
      former criterion). The results of PCR, restriction fragment profiles, and
      Southern DNA-DNA hybridizations of the profiles all indicated that such larger
      pSCVs were derived from the 50-kb plasmid recombined with non-pSCVs found in some
      clinical isolates. Fifteen of the 17 strains, including a laboratory strain, were
      then tested for drug resistance against 16 antibiotics with E-test and the
      dilution method. The laboratory strain, which harbored a 50-kb pSCV and a 6-kb
      non-pSCV, was resistant only to sulfonamides (SUL), and its resistance gene,
      sulII, checked with PCR and DNA-DNA hybridization, was located on the 6-kb non
      pSCV. All 14 clinical strains were resistant to multiple drugs. Of the 14, 7 were
      resistant to SUL, and the resistance gene was located on a plasmid. The sulII
      gene, but not bla(TEM-1), was carried only on the 6-kb non-pSCV. Of the remaining
      six large plasmids, three of 90 kb, two of 136 kb, and one of 140 kb, the last
      three were pSCVs and carried the other SUL gene (sulI) and the bla(TEM-1) gene.
      The six strains were also resistant to trimethoprim-sulfamethoxazole. None of the
      50-kb pSCVs carried resistance genes. These drug resistance genes on the large
      pSCVs were apparently also acquired through recombination.

PMID- 11451687
TI  - Novel class A beta-lactamase Sed-1 from Citrobacter sedlakii: genetic diversity
      of beta-lactamases within the Citrobacter genus.
AB  - Citrobacter sedlakii 2596, a clinical strain resistant to aminopenicillins,
      carboxypenicillins, and early cephalosporins such as cephalothin, but remaining
      susceptible to acylureidopenicillins, carbapenems, and later cephalosporins such
      as cefotaxime, was isolated from the bile of a patient treated with beta-lactam
      and quinolone antibiotics. The isolate produced an inducible class A beta
      lactamase of pI 8.6, named Sed-1, which was purified. Characterized by a
      molecular mass of 30 kDa, Sed-1 preferentially hydrolyzed benzylpenicillin,
      cephalothin, and cloxacillin. The corresponding gene, bla(Sed-1), was cloned and
      sequenced. Its deduced amino acid sequence shared more than 60% identity with the
      chromosome-encoded beta-lactamases from Citrobacter koseri (formerly C. diversus)
      (84%), Klebsiella oxytoca (74%), Serratia fonticola (67%), and Proteus vulgaris
      (63%) and 71% identity with the plasmid-mediated enzyme MEN-1. A gene coding for
      a LysR transcriptional regulator was found upstream from bla(Sed-1). This
      regulator, named SedR, displayed 90% identity with the AmpR sequence of the
      chromosomal beta-lactamase from C. koseri and 63 and 50% identity with the AmpR
      sequences of P. vulgaris and Enterobacter cloacae, respectively. By using DNA-DNA
      hybridization, a bla(Sed-1)-like gene was identified in two reference strains, C.
      sedlakii (CIP-105037) and Citrobacter rodentium (CIP-104675), but not in the 18
      strains of C. koseri studied. Two DNA fragments were amplified and sequenced from
      the reference strains of C. sedlakii CIP-105037 and C. rodentium CIP-104675 using
      two primers specific for bla(Sed-1). They shared 98 and 80% identity with bla(Sed
      1), respectively, confirming the diversity of the chromosomally encoded class A
      beta-lactamases found in Citrobacter.

PMID- 11451689
TI  - Efficacy of linezolid in treatment of experimental endocarditis caused by
      methicillin-resistant Staphylococcus aureus.
AB  - The efficacies of orally (p.o.) dosed linezolid and intravenously (i.v.) dosed
      vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in rabbits
      with experimental aortic-valve endocarditis were investigated. After endocarditis
      was established with a recent clinical MRSA isolate, rabbits were dosed for 5
      days with linezolid (p.o., three times a day) at either 25, 50, or 75 mg/kg of
      body weight or vancomycin (i.v., twice a day) at 25 mg/kg. The 25-mg/kg linezolid
      group had a high mortality rate and bacterial counts in the valve vegetations
      that were not different from those of the controls. Linezolid dosed p.o. at 50
      and 75 mg/kg and i.v. vancomycin produced statistically significant reductions in
      bacterial counts compared to those of the untreated controls. The reduced
      bacterial counts and culture-negative valve rates for the animals treated with
      linezolid at 75 mg/kg were similar to those for the vancomycin-treated animals.
      Concentrations of linezolid in plasma were determined at several points in the
      dosing regimen. These results suggest that the efficacy of linezolid in this
      infection model is related to trough levels in plasma that remain above the MIC
      for this microorganism. At the ineffective dose of linezolid (25 mg/kg) the
      concentration at sacrifice was 0.045 times the MIC, whereas the concentrations of
      linezolid in plasma in the 50- and 75-mg/kg groups were 2 and 5 times the MIC at
      sacrifice, respectively. The results from this experimental model suggest that
      the oxazolidinone linezolid may be effective for the treatment of serious
      staphylococcal infections when resistance to other antimicrobials is present.

PMID- 11451690
TI  - Kappacin, a novel antibacterial peptide from bovine milk.
AB  - Caseinomacropeptide (CMP) is a heterogeneous C-terminal fragment (residues 106 to
      169) of bovine milk kappa-casein composed of glycosylated and phosphorylated
      forms of different genetic variants. We have demonstrated that CMP has growth
      inhibitory activity against the oral opportunistic pathogens Streptococcus mutans
      and Porphyromonas gingivalis and against Escherichia coli. CMP was fractionated
      using reversed-phase high-performance liquid chromatography (RP-HPLC), and each
      fraction was tested for activity against S. mutans in a 96-well-plate broth
      assay. Fractions were characterized by N-terminal sequence analysis and mass
      spectrometry. The active form of CMP was shown to be the nonglycosylated,
      phosphorylated kappa-casein (residues 106 to 169) [kappa-casein(106--169)], which
      we have designated kappacin. Endoproteinase Glu-C was used to hydrolyze CMP, and
      the generated peptides were separated using RP-HPLC and gel filtration-HPLC and
      then tested for activity against S. mutans. The peptide Ser(P)(149)kappa-casein
      A(138--158) was the only peptide generated by endoproteinase Glu-C digestion that
      exhibited growth-inhibitory activity. Peptides corresponding to the sequences of
      the inhibitory peptide Ser(P)(149)kappa-casein-A(138--158) and its
      nonphosphorylated counterpart kappa-casein-A(138--158) were chemically
      synthesized and tested for antibacterial activity. The synthetic Ser(P)(149)
      kappa-casein-A(138--158) displayed growth-inhibitory activity against S. mutans
      (MIC, 59 microg/ml [26 microM]). The nonphosphorylated peptide, however, did not
      inhibit growth at the concentrations tested, indicating that phosphorylation is
      essential for activity.

PMID- 11451691
TI  - Intravenous infusion of cereport increases uptake and efficacy of acyclovir in
      herpes simplex virus-infected rat brains.
AB  - The outcome of herpes simplex virus (HSV) infections manifesting as encephalitis
      in healthy or immunocompromised individuals is generally very poor with mortality
      rates of about 8 to 28% with treatment. The long-term prognosis of survivors is
      often problematic, posing the need for alternative treatments that may decrease
      the mortality and morbidity associated with herpes encephalitis. This study
      addresses one such approach that includes a temporary permeabilization of the
      blood-brain barrier during treatment with acyclovir (ACV). In these studies we
      utilized a synthetic bradykinin analog, Cereport (RMP-7), in conjunction with ACV
      to treat HSV infection of the brain in a rat model. Cereport, infused
      intravenously via the jugular vein, was shown to increase [(14)C]ACV uptake in
      both the HSV-1-infected and -uninfected rat brain by approximately two- to
      threefold, correlating with enhanced efficacy of ACV in various brain
      compartments. In another series of experiments to determine efficacy, various
      doses of unlabeled ACV were administered during infusion with RMP-7. The decrease
      in viral titers in the temporal regions of the brain after 5 days of treatment
      suggested that this approach enhanced the efficacy of ACV treatment. These data
      indicated that Cereport infused with ACV enhances both the penetration and
      efficacy of this drug in the treatment of an experimental HSV-1 infection of the
      rat brain.

PMID- 11451692
TI  - Molecular characterization of chromosomal class C beta-lactamase and its
      regulatory gene in Ochrobactrum anthropi.
AB  - Ochrobactrum anthropi, formerly known as CDC group Vd, is an oxidase-producing,
      gram-negative, obligately aerobic, non-lactose-fermenting bacillus of low
      virulence that occasionally causes human infections. It is highly resistant to
      all beta-lactams except imipenem. A clinical isolate, SLO74, and six reference
      strains were tested. MICs of penicillins, aztreonam, and most cephalosporins
      tested, including cefotaxime and ceftazidime, were >128 microg/ml and of cefepime
      were 64 to >128 microg/ml. Clavulanic acid was ineffective and tazobactam had a
      weak effect in association with piperacillin. Two genes, ampR and ampC, were
      cloned by inserting restriction fragments of genomic DNA from the clinical strain
      O. anthropi SLO74 into pBK-CMV to give the recombinant plasmid pBK-OA1. The
      pattern of resistance to beta-lactams of this clone was similar to that of the
      parental strain, except for its resistance to cefepime (MIC, 0.5 ,micro/ml). The
      deduced amino acid sequence of the AmpC beta-lactamase (pI, 8.9) was only 41 to
      52% identical to the sequence of other chromosomally encoded and plasmid-encoded
      class C beta-lactamases. The kinetic properties of this beta-lactamase were
      typical for this class of beta-lactamases. Upstream from the ampC gene, the ampR
      gene encodes a protein with a sequence that is 46 to 62% identical to those of
      other AmpR proteins and with an amino-terminal DNA-binding domain typical of
      transcriptional activators of the Lys-R family. The deduced amino acid sequences
      of the ampC genes of the six reference strains were 96 to 99% identical to the
      sequence of the clinical strain. The beta-lactamase characterized from strain
      SLO74 was named OCH-1 (gene, bla(OCH-I)).

PMID- 11451693
TI  - Mutation in Serratia marcescens AmpC beta-lactamase producing high-level
      resistance to ceftazidime and cefpirome.
AB  - Starting from a clinical isolate of Serratia marcescens that produced a
      chromosomally encoded AmpC beta-lactamase inducibly, we isolated by stepwise
      selection two laboratory mutants that showed high levels of resistance to some
      cephalosporins. The 98R mutant apparently overproduced the unaltered beta
      lactamase constitutively, but the 520R mutant produced an altered enzyme, also
      constitutively. Ceftazidime and cefpirome MICs for the 520R mutant were much
      higher (512 and 64 microg/ml, respectively) than those for the 98R mutant (16 and
      16 microg/ml, respectively). Yet the MICs of cephaloridine and piperacillin for
      the 520R mutant were four- to eightfold lower than those for the 98R mutant.
      Cloning and sequencing of the ampC alleles showed that in the 520R mutant enzyme,
      the Thr64 residue, about two turns away from the active-site serine, was mutated
      to isoleucine. This resulted in a >1,000-fold increase in the catalytic
      efficiency (k(cat)/K(m)) of the mutated AmpC enzyme toward ceftazidime, whereas
      there was a >10-fold decrease in the efficiency of the mutant enzyme toward
      cefazolin and cephaloridine. The outer membrane permeability of the 520R strain
      to cephalosporins was also less than in the 98R strain, and the alteration of the
      kinetic properties of the AmpC enzyme together with this difference in
      permeability explained quantitatively the resistance levels of both mutant
      strains to most agents studied.

PMID- 11451694
TI  - GT160-246, a toxin binding polymer for treatment of Clostridium difficile
      colitis.
AB  - GT160-246, a high-molecular-weight soluble anionic polymer, was tested in vitro
      and in vivo for neutralization of Clostridium difficile toxin A and B activities.
      Five milligrams of GT160-246 per ml neutralized toxin-mediated inhibition of
      protein synthesis in Vero cells induced by 5 ng of toxin A per ml or 1.25 ng of
      toxin B per ml. In ligated rat ileal loops, 1 mg of GT160-246 neutralized fluid
      accumulation caused by 5 microg of toxin A. At doses as high as 80 mg/loop,
      cholestyramine provided incomplete neutralization of fluid accumulation caused by
      5 microg of toxin A. GT160-246 protected 80% of the hamsters from mortality
      caused by infection with C. difficile, whereas cholestyramine protected only 10%
      of animals. Treatment of C. difficile-infected hamsters with metronidazole
      initially protected 100% of the hamsters from mortality, but upon removal of
      treatment, 80% of the hamsters had relapses and died. In contrast, removal of
      GT160-246 treatment did not result in disease relapse in the hamsters. GT160-246
      showed no antimicrobial activity in tests with a panel of 16 aerobic bacteria and
      yeast and 22 anaerobic bacteria and did not interfere with the in vitro
      activities of most antibiotics. GT160-246 offers a novel, nonantimicrobial
      treatment of C. difficile disease in humans.

PMID- 11451695
TI  - Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is
      associated with mutations in gyrA.
AB  - Clostridium difficile is the etiological agent of antibiotic-associated colitis
      and the most common cause of hospital-acquired infectious diarrhea.
      Fluoroquinolones such as ciprofloxacin are associated with lower risks of C.
      difficile-associated diarrhea. In this study, we have analyzed 72 C. difficile
      isolates obtained from patients with different clinical courses of disease, such
      as toxic megacolon and relapses; the hospital environment; public places; and
      horses. They were investigated for their susceptibilities to moxifloxacin (MXF),
      metronidazole (MEO), and vancomycin (VAN). Mutants highly resistant to
      fluoroquinolones were selected in vitro by stepwise exposure to increasing
      concentrations of MXF. The resulting mutants were analyzed for the presence of
      mutations in the quinolone resistance-determining regions of DNA gyrase (gyrA),
      the production of toxins A and B, and the epidemiological relationship of these
      isolates. These factors were also investigated using PCR-based methods. All
      strains tested were susceptible to MEO and VAN. Twenty-six percent of the
      clinical isolates (19 of 72) were highly resistant to MXF (MIC > or = 16
      microg/ml). Fourteen of these 19 strains contained nucleotide changes resulting
      in amino acid substitutions at position 83 in the gyrA protein. Resistant strains
      selected in vitro did not contain mutations at that position. These findings
      indicate that resistance to MXF in a majority of cases may be due to amino acid
      substitution in the gyrA gene.

PMID- 11451696
TI  - Clearance of fungal burden during treatment of disseminated histoplasmosis with
      liposomal amphotericin B versus itraconazole.
AB  - Animal studies have shown that fungal burden correlates with survival during
      treatment with new antifungal therapies for histoplasmosis. The purpose of this
      report is to compare the clearance of fungal burden in patients with
      histoplasmosis treated with liposomal amphotericin B versus itraconazole. In two
      separate closed clinical trials that evaluated the efficacy of liposomal
      amphotericin B and itraconazole treatment of disseminated histoplasmosis in
      patients with AIDS, blood was cultured for fungus and blood and urine were tested
      for Histoplasma antigen. The clinical response rates were similar; 86% with
      liposomal amphotericin B (n = 51) versus 85% with itraconazole (n = 59). Of the
      patients with positive blood cultures at enrollment, after 2 weeks of therapy
      cultures were negative in over 85% of the liposomal amphotericin B group versus
      53% of the itraconazole group (P = 0.0008). Furthermore, after 2 weeks, median
      antigen levels in serum fell by 1.6 U in the liposomal amphotericin B group
      versus 0.1 U in the itraconazole group (P = 0.02), and those in urine fell by 2.1
      U in the liposomal amphotericin B group and 0.2 U in the itraconazole group (P =
      0.0005). The more rapid clearance of fungemia supports the use of liposomal
      amphotericin B rather than itraconazole for initial treatment of moderately
      severe or severe histoplasmosis.

PMID- 11451697
TI  - Once-daily oral gatifloxacin versus oral levofloxacin in treatment of
      uncomplicated skin and soft tissue infections: double-blind, multicenter,
      randomized study.
AB  - This was a double-blind, multicenter study in which 410 adults (> or =18 years of
      age) with uncomplicated skin and soft tissue infections (SSTIs) were randomized
      to receive either 400 mg of gatifloxacin orally once daily or 500 mg of
      levofloxacin orally once daily for 7 to 10 days. The study protocol called for
      four assessments-before and during treatment, at the end of treatment, and
      posttreatment. Efficacy evaluations included clinical response and bacterial
      eradication rates. Of 407 treated patients, 202 (108 women, 94 men) received
      gatifloxacin and 205 (111 women, 94 men) received levofloxacin. For clinically
      evaluable patients, the cure rates were 91% for gatifloxacin and 84% for
      levofloxacin (95% confidence interval [CI] for the difference, -2.0 to 15.2%).
      Clinical cure rates for microbiologically evaluable patients were 93% for
      gatifloxacin and 88% for levofloxacin (95% CI for the difference, -6.5 to 16.8%).
      The bacterial eradication rate was 92% for each group, with gatifloxacin
      eradicating 93% of the methicillin-susceptible Staphylococcus aureus isolates and
      levofloxacin eradicating 91% of them. Both drugs were well tolerated. Most of the
      adverse events were mild to moderate, and nausea was the most common adverse
      event in each treatment arm. Once-daily oral gatifloxacin (400 mg) is clinically
      efficacious and well tolerated compared with once-daily levofloxacin (500 mg) for
      the treatment of patients with uncomplicated SSTIs.

PMID- 11451698
TI  - In vitro activities of ABT-773, a new ketolide, against aerobic and anaerobic
      pathogens isolated from antral sinus puncture specimens from patients with
      sinusitis.
AB  - The comparative in vitro activities of ABT-773 against 207 aerobic and 162
      anaerobic antral sinus puncture isolates showed that erythromycin-resistant
      pneumococcal strains were susceptible to ABT-773 (< or =0.125 microg/ml); the MIC
      at which 90% of the isolates tested were inhibited for Haemophilus influenzae and
      other Haemophilus spp. was 4 microg/ml; and all Moraxella spp. and beta-lactamase
      producing Prevotella species strains were inhibited by < or =0.125 microg/ml.
      Among the anaerobes tested, only fusobacteria (45%) required > or =4 microg of
      ABT-773/ml for inhibition. ABT-773 may offer a therapeutic alternative for sinus
      infections.

PMID- 11451699
TI  - Identification of a plasmid encoding SHV-12, TEM-1, and a variant of IMP-2
      metallo-beta-lactamase, IMP-8, from a clinical isolate of Klebsiella pneumoniae.
AB  - A multidrug-resistant plasmid encoding TEM-1, SHV-12, and a variant of IMP-2
      metallo-beta-lactamase, designated IMP-8, was identified from a clinical isolate
      of Klebsiella pneumoniae. There are four nucleotide differences between bla(IMP
      2) and bla(IMP-8), resulting in two amino acid differences. bla(IMP-8) was also
      found to be carried by an integron-borne gene cassette similar to the bla(IMP-2)
      cassette.

PMID- 11451700
TI  - In vitro activities of MK-0826 and 16 other antimicrobials against Bacteroides
      fragilis group strains.
AB  - The activity of MK-0826, a new carbapenem, against 309 Bacteroides fragilis group
      strains was investigated and compared with that of 11 other beta-lactam and 5 non
      beta-lactam agents. MK-0826 showed excellent activity (MICs ranged from < or
      =0.06 to 4 microg/ml). The new carbapenem may be useful in the treatment of mixed
      anaerobic infections involving B. fragilis group strains.

PMID- 11451701
TI  - Prevalence of macrolide resistance genes in clinical isolates of the
      Streptococcus anginosus ("S. milleri") group.
AB  - Twenty-two unrelated erythromycin-resistant anginosus group strains (3.2%
      resistance rate) were assessed for mechanisms of resistance. Streptococcus
      anginosus accounted for 16 of the 22 isolates. Fifteen isolates harbored the
      erm(B) gene. The erm(TR) and the mef(E) genes were carried by two isolates each.
      In three isolates, none of these resistance genes was detected by PCR.

PMID- 11451702
TI  - Mutation in the DNA gyrase A Gene of Escherichia coli that expands the quinolone
      resistance-determining region.
AB  - In three Escherichia coli mutants, a change (Ala-51 to Val) in the gyrase A
      protein outside the standard quinolone resistance-determining region (QRDR)
      lowered the level of quinolone susceptibility more than changes at amino acids
      67, 82, 84, and 106 did. Revision of the QRDR to include amino acid 51 is
      indicated.

PMID- 11451703
TI  - Nonenzymatic chloramphenicol resistance mediated by IncC plasmid R55 is encoded
      by a floR gene variant.
AB  - The IncC plasmid R55, initially described in the 1970s and isolated from
      Klebsiella pneumoniae, confers nonenzymatic chloramphenicol resistance. The gene
      coding for this resistance was cloned and sequenced and shows 95 to 97%
      nucleotide identity with the recently reported floR gene from Salmonella enterica
      serovar Typhimurium DT104 and from Escherichia coli animal isolates,
      respectively, conferring cross-resistance to florfenicol.

PMID- 11451704
TI  - Influence of liposomal amphotericin B on CD8 T-cell function.
AB  - Liposomal amphotericin B was immunosuppressive on target cell lysis in vitro and
      on protection mediated by cytotoxic CD8 T cells in murine listeriosis. When
      dosages usually used for therapy in humans were compared, the immunosuppressive
      effect of 5 mg of liposomal amphotericin B/kg of body weight/day was similar to
      that of standard amphotericin B at 1 mg/kg/day, but a dosage of liposomal
      amphotericin B of 1 mg/kg/day was not suppressive in vivo.

PMID- 11451705
TI  - Cloning and biochemical characterization of a class A beta-lactamase from
      Prevotella intermedia.
AB  - The gene encoding a beta-lactamase of Prevotella intermedia was cloned and
      sequenced. This gene, called cfxA2, shared 98% identity with cfxA, the structural
      gene of a beta-lactamase previously described in Bacteroides vulgatus. The
      deduced protein sequence had a K272E substitution. CfxA2 had the characteristics
      of class A, group 2e beta-lactamases.

PMID- 11451706
TI  - Activities of gemifloxacin and five other antimicrobial agents against Listeria
      monocytogenes and coryneform bacteria isolated from clinical samples.
AB  - The in vitro activities of gemifloxacin, ciprofloxacin, ampicillin, doxycycline,
      gentamicin, and vancomycin were evaluated against 15 Listeria monocytogenes
      strains and 205 coryneform bacteria isolated from clinical samples. The
      percentages of strains inhibited by gemifloxacin at 0.5 microg/ml were 100% (L.
      monocytogenes), 93.3% (Brevibacterium spp.), 90% (Corynebacterium minutissimum),
      42.5% (Corynebacterium amycolatum), 20% (Corynebacterium striatum), 12.5%
      (Corynebacterium jeikeium), and 10% (Corynebacterium urealyticum). One hundred
      percent of the L. monocytogenes strains were inhibited by 0.25 microg of
      gemifloxacin per ml, whereas 0% of the strains were inhibited by 0.25 microg of
      ciprofloxacin per ml. Vancomycin at 2 microg/ml inhibited all strains.
      Doxycycline and gentamicin at 4 microg/ml inhibited 94 and 49% of the strains,
      respectively, while ampicillin at 0.5, 2, and 8 microg/ml inhibited 24, 61, and
      66% of the strains, respectively. It is concluded that gemifloxacin shows good in
      vitro activity against L. monocytogenes and coryneform bacteria except C.
      jeikeium and C. urealyticum.

PMID- 11451707
TI  - Alterations in MurM, a cell wall muropeptide branching enzyme, increase high
      level penicillin and cephalosporin resistance in Streptococcus pneumoniae.
AB  - We report that alteration in MurM, an enzyme involved in the biosynthesis of
      branched-stem cell wall muropeptides, is required for maximal expression of
      penicillin and cefotaxime resistance in the pneumococcus. Hungarian isolate 3191
      (penicillin MIC, 16 microg/ml; cefotaxime MIC, 4 microg/ml) was a source of donor
      DNA in transformation experiments. Penicillin-binding protein DNA was
      insufficient to transform recipient strain R6 to full resistance. Further
      transformation with altered murM DNA was required for full expression of donor
      penicillin and cefotaxime resistance.

PMID- 11451708
TI  - Immunoprecipitation of [(3)H]dihydroartemisinin translationally controlled tumor
      protein (TCTP) adducts from Plasmodium falciparum-infected erythrocytes by using
      anti-TCTP antibodies.
AB  - Artemisinin and its derivatives are endoperoxide-containing antimalarial drugs
      that appear to form adducts in situ with the Plasmodium falciparum
      translationally controlled tumor protein (TCTP) homolog. Immunoprecipitation with
      antibody to recombinant TCTP suggests that adducts may form with both monomeric
      and dimeric TCTP.

PMID- 11451709
TI  - Antibiotic susceptibility and mechanisms of erythromycin resistance in clinical
      isolates of Streptococcus agalactiae: French multicenter study.
AB  - Among 126 Streptococcus agalactiae isolates collected in 10 French laboratories
      in 1999, 27 (21.4%) had macrolide resistance related to the presence of erm(B)
      (11 strains), erm(A) subclass erm(TR) (10 strains), and mef(A) genes (2 strains)
      and the presence of combinations of erm(B) and erm(A) genes or mef(A) genes (3
      strains).

PMID- 11451710
TI  - The public health implications of the Dietary Approaches to Stop Hypertension
      Trial.

PMID- 11451711
TI  - Plasma concentrations of total homocysteine predict mortality risk.

PMID- 11451712
TI  - The future of phytochemical databases.

PMID- 11451713
TI  - Treatment of protein-energy malnutrition in chronic nonmalignant disorders.
AB  - Protein-energy malnutrition (PEM) is common in connection with chronic disease
      and is associated with increased morbidity and mortality. Because the risk of PEM
      is related to the degree of illness, the causal connections between malnutrition
      and a poorer prognosis are complex. It cannot automatically be inferred that
      nutritional support will improve the clinical course of patients with wasting
      disorders. We reviewed studies of the treatment of PEM in cases of chronic
      obstructive pulmonary disease, chronic heart failure, stroke, dementia,
      rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis,
      and multiple disorders in the elderly. Several methodologic problems are
      associated with nutrition treatment studies in chronically ill patients. These
      problems include no generally accepted definition of PEM, uncertain patient
      compliance with supplementation, and a wide range of outcome variables. Avail
      able treatment studies indicate that dietary supplements, either alone or in
      combination with hormonal treatment, may have positive effects when given to
      patients with manifest PEM or to patients at risk of developing PEM. In chronic
      obstructive pulmonary disease, nutritional treatment may improve respiratory
      function. Nutritional therapy of elderly women after hip fractures may speed up
      the rehabilitation process. When administered to elderly patients with multiple
      disorders, diet therapy may improve functional capacity. The data regarding
      nutritional treatment of the conditions mentioned above is still inconclusive.
      There is still a great need for randomized controlled long-term studies of the
      effects of defined nutritional intervention programs in chronically ill and frail
      elderly with a focus on determining clinically relevant outcomes.

PMID- 11451714
TI  - Glutamine: commercially essential or conditionally essential? A critical
      appraisal of the human data.
AB  - Glutamine is a nonessential amino acid that can be synthesized from glutamate and
      glutamic acid by glutamate-ammonia ligase. Glutamine is an important fuel source
      for the small intestine. It was proposed that glutamine is necessary for the
      maintenance of normal intestinal morphology and function in the absence of
      luminal nutrients. However, intestinal morphologic and functional changes related
      to enteral fasting and parenteral nutrition are less significant in humans than
      in animal models and may not be clinically significant. Therefore, it is unclear
      whether glutamine is necessary for the preservation of normal intestinal
      morphology and function in humans during parenteral nutrition. It was suggested
      that both glutamine-supplemented parenteral nutrition and enteral diets may pre
      vent bacterial translocation via the preservation and augmentation of small bowel
      villus morphology, intestinal permeability, and intestinal immune function.
      However, it is unclear whether clinically relevant bacterial translocation even
      occurs in humans, much less whether there is any value in the prevention of such
      occurrences. Results of the therapeutic use of glutamine in humans at
      nonphysiologic doses indicate limited efficacy. Although glutamine is generally
      recognized to be safe on the basis of relatively small studies, side effects in
      patients receiving home parenteral nutrition and in those with liver-function
      abnormalities have been described. Therefore, on the basis of currently available
      clinical data, it is inappropriate to recommend glutamine for therapeutic use in
      any condition.

PMID- 11451715
TI  - Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a
      National Cholesterol Education Program Step I diet.
AB  - BACKGROUND: Plant sterol esters reduce cholesterol absorption and lower
      circulating blood cholesterol concentrations when incorporated into the habitual
      diet. OBJECTIVE: This randomized, double-blind, 3-group parallel, controlled
      study evaluated the influence of esterified plant sterols on serum lipid
      concentrations in adults with mild-to-moderate primary hypercholesterolemia.
      DESIGN: Subjects incorporated a conventional 50%-fat spread into a National
      Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by
      a 5-wk intervention period of the diet plus either a control reduced-fat spread
      (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to
      achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high
      sterol group). RESULTS: Subjects in the low- and high-sterol groups who consumed
      > or = 80% of the scheduled servings (per-protocol analyses) had total
      cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that
      were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower,
      and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower,
      respectively, than values for the control group (P < 0.001 for all).
      Additionally, triacylglycerol concentrations decreased by 10.4% in the high
      sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were
      generally within reference ranges at baseline and postintervention. Serum plant
      sterol concentrations increased from baseline (0.48% of total sterol by wt) to
      0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05
      compared with control). CONCLUSION: A reduced-fat spread containing plant sterol
      esters incorporated into a low-fat diet is a beneficial adjunct in the dietary
      management of hypercholesterolemia.

PMID- 11451716
TI  - Fecal steroids of the coprolite of a Greenland Eskimo mummy, AD 1475: a clue to
      dietary sterol intake.
AB  - BACKGROUND: Sterols in feces reflect sterols in the diet. In previous analyses of
      the fecal steroids in 1000-2000-y-old Native American coprolites found in the dry
      caves of Nevada, we showed that the sterol nucleus was stable. The coprolites
      provided useful dietary information. OBJECTIVE: In the present study, we analyzed
      the fecal steroids of an Eskimo mummy buried and frozen >500 y ago in Greenland.
      We compared these analyses with our findings in the coprolites from Nevada and in
      present-day stool samples from Tarahumara Indians of Mexico and Americans
      consuming low- and high-cholesterol diets. DESIGN: The fecal material from the
      Eskimo mummy was subjected to saponification, extraction, and digitonin
      precipitation. The sterols and bile acids were further analyzed by thin-layer
      chromatography and gas-liquid chromatography. RESULTS: The fecal steroids of the
      Greenland Eskimo mummy were remarkably similar to those of present-day stool
      samples. However, unlike in the stool of modern humans, a portion of the neutral
      steroids in the coprolite had been converted to sterol epimers. Instead of
      deoxycholic acid, 3alpha,6beta,12alpha-trihydroxycholanic acid was one of the
      major fecal bile acids. The plant sterol output in the coprolite was only 0.4% of
      the output of Americans consuming 250-400 mg plant sterols/d. The ratio of bile
      acid to cholesterol in the coprolite was similar to that in stool from Tarahumara
      Indians consuming a low-cholesterol diet. CONCLUSION: The sterol nucleus is
      stable when frozen. The analysis of coprolite showed that the young Eskimo woman
      had consumed a diet very low in plant sterols and moderate to low in cholesterol
      content.

PMID- 11451717
TI  - Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced
      early after an acute myocardial infarction on serum triacylglycerol and HDL
      cholesterol.
AB  - BACKGROUND: Results of epidemiologic studies and clinical trials indicate that
      moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and
      may improve prognosis. OBJECTIVE: The objective was to evaluate the effect of a
      high-dose ethylester concentrate of n-3 fatty acids administered early after an
      acute myocardial infarction (MI) on subsequent cardiac events and serum lipids.
      DESIGN: Three hundred patients with acute MI were randomly assigned to a daily
      dose of either 4 g highly concentrated n-3 fatty acids or corn oil, administered
      in a double-blind manner over 12-24 mo. Median follow-up time was 1.5 y. Clinical
      follow-up, including the drawing of blood samples, was performed after 6 wk of
      treatment and later at 0.5-year intervals. RESULTS: Forty-two (28%) patients in
      the n-3 group and 36 (24%) in the corn oil group experienced at least one cardiac
      event (cardiac death, resuscitation, recurrent MI, or unstable angina). No
      significant difference in prognosis was observed between groups for single or
      combined cardiac events. Total cholesterol concentrations decreased in both
      groups, with no significant intergroup differences. On average, the monthly
      increase in HDL cholesterol was 1.11% in the n-3 group and 0.55% in the corn oil
      group (P = 0.0016). Triacylglycerol concentrations decreased by 1.30%/mo in the n
      3 group, whereas they increased by 0.35%/mo in the corn oil group (P < 0.0001).
      CONCLUSION: No clinical benefit of a high-dose concentrate of n-3 fatty acids
      compared with corn oil was found despite a favorable effect on serum lipids.

PMID- 11451718
TI  - High-protein diets in hyperlipidemia: effect of wheat gluten on serum lipids,
      uric acid, and renal function.
AB  - BACKGROUND: The metabolic effects of diets high in vegetable protein have not
      been assessed despite much recent interest in the effect of soy proteins in
      reducing serum cholesterol. OBJECTIVE: We assessed the metabolic effects of diets
      high in vegetable protein (specifically, wheat gluten) on serum lipids, uric acid
      concentrations, and renal function. DESIGN: Twenty hyperlipidemic men and women
      consumed isoenergetic test (high-protein) and control metabolic diets for 1 mo in
      a randomized crossover design. In the high-protein diet, 11% of the total dietary
      energy from starch in the control bread was replaced by vegetable protein (wheat
      gluten), resulting in 27% of total energy from protein compared with 16% in the
      control diet. In other respects, the 2 diets were identical. RESULTS: Compared
      with the control, the high-protein diet resulted in lower serum concentrations of
      triacylglycerol (by 19.2 +/- 5.6%; P = 0.003), uric acid (by 12.7 +/- 2.0%; P <
      0.001), and creatinine (by 2.5 +/- 1.1%; P = 0.035) and higher serum
      concentrations of urea (by 42.2 +/- 5.8%; P < 0.001) and a higher 24-h urinary
      urea output (by 99.2 +/- 17.2%; P < 0.001). No significant differences were
      detected in total or HDL cholesterol or in the renal clearance of creatinine. LDL
      oxidation, assessed as the ratio of conjugated dienes to LDL cholesterol in the
      LDL fraction, was lower with the high-protein diet (by 10.6 +/- 3.6%; P = 0.009).
      CONCLUSIONS: High intakes of vegetable protein from gluten may have beneficial
      effects on cardiovascular disease risk by reducing oxidized LDL, serum
      triacylglycerol, and uric acid. Further studies are required to assess the longer
      term effects on renal function.

PMID- 11451719
TI  - Association of sex, adiposity, and diet with HDL subclasses in middle-aged
      Chinese.
AB  - BACKGROUND: There is limited information regarding the associations of lifestyle
      factors and sex with HDL subclasses containing apolipoprotein (apo) A-I (Lp A-I)
      and both apo A-I and apo A-II (Lp A-I:A-II). OBJECTIVE: We sought to examine the
      relations between 2 major HDL subclasses and sex, menopausal status, nutrient
      intakes, and adiposity. DESIGN: We conducted interviews and measured blood
      variables in 409 government employees aged 40-59 y in Taiwan. RESULTS: Women (n =
      203) had significantly higher concentrations of HDL cholesterol, Lp A-I, and Lp A
      I:A-II than did men (n = 206). Postmenopausal women (n = 72) had higher
      concentrations of HDL cholesterol, Lp A-I, and Lp A-I:A-II than did premenopausal
      women (n = 131). Body mass index and waist-to-hip ratio were strong predictors of
      and exerted an independent additive effect on Lp A-I concentrations in both men
      and women. However, body adiposity was associated with Lp A-I:A-II concentrations
      only in men. Waist-to-hip ratio was an independent determinant of Lp A-I but not
      of Lp A-I:A-II in men and postmenopausal women after adjustment for age, body
      mass index, smoking, and diet. Although there were relatively weak associations
      between dietary factors and both HDL subclasses (r = 0.01-0.26) in men and women
      according to bivariate analyses, multiple regression models showed that total
      fat, saturated fat, and cholesterol intakes were significantly correlated with
      HDL cholesterol and both Lp A-I and Lp A-I:A-II in men, but not in women.
      CONCLUSION: Our data suggest that body adiposity and dietary fat consumption
      affect 2 major HDL subclasses differently depending on subject sex and menopausal
      status.

PMID- 11451720
TI  - Effects of walnut consumption on plasma fatty acids and lipoproteins in combined
      hyperlipidemia.
AB  - BACKGROUND: Epidemiologic studies show an inverse relation between nut
      consumption and coronary heart disease. OBJECTIVE: We determined the effects of
      walnut intake on plasma fatty acids, lipoproteins, and lipoprotein subclasses in
      patients with combined hyperlipidemia. DESIGN: Participants sequentially adhered
      to the following diets: 1) a habitual diet (HD), 2) a habitual diet plus walnuts
      (HD+W), 3) a low-fat diet (LFD), and 4) a low-fat diet plus walnuts (LFD+W).
      RESULTS: In 13 postmenopausal women and 5 men ( +/- SD age 60 +/- 8 y), walnut
      supplementation did not increase body weight despite increased energy intake and
      the LFD caused weight loss (1.3 +/- 0.5 kg; P < 0.01). When comparing the HD with
      the HD+W, linoleic acid concentrations increased from 29.94 +/- 1.14% to 36.85 +/
      1.13% and alpha-linolenic acid concentrations increased from 0.78 +/- 0.04% to
      1.56 +/- 0.11%. During the LFD+W, plasma total cholesterol concentrations
      decreased by 0.58 +/- 0.16 mmol/L when compared with the HD and by 0.46 +/- 0.14
      mmol/L when compared with the LFD. LDL-cholesterol concentrations decreased by
      0.46 +/- 0.15 mmol/L when compared with the LFD. Measurements of lipoprotein
      subclasses and particle size suggested that walnut supplementation lowered
      cholesterol preferentially in small LDL (46.1 +/- 1.9% compared with 33.4 +/-
      4.3%, HD compared with HD+W, respectively; P < 0.01). HDL-cholesterol
      concentrations decreased from 1.27 +/- 0.07 mmol/L during the HD to 1.14 +/- 0.07
      mmol/L during the HD+W and to 1.11 +/- 0.08 mmol/L during the LFD. The decrease
      was seen primarily in the large HDL particles. CONCLUSIONS: Walnut
      supplementation may beneficially alter lipid distribution among various
      lipoprotein subclasses even when total plasma lipids do not change. This may be
      an additional mechanism underlying the antiatherogenic properties of nut intake.

PMID- 11451721
TI  - Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches
      to Stop Hypertension (DASH) Trial.
AB  - BACKGROUND: Effects of diet on blood lipids are best known in white men, and
      effects of type of carbohydrate on triacylglycerol concentrations are not well
      defined. OBJECTIVE: Our goal was to determine the effects of diet on plasma
      lipids, focusing on subgroups by sex, race, and baseline lipid concentrations.
      DESIGN: This was a randomized controlled outpatient feeding trial conducted in 4
      field centers. The subjects were 436 participants of the Dietary Approaches to
      Stop Hypertension (DASH) Trial [mean age: 44.6 y; 60% African American; baseline
      total cholesterol: < or = 6.7 mmol/L (< or = 260 mg/dL)]. The intervention
      consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or
      a diet increased in fruit, vegetables, and low-fat dairy products and reduced in
      saturated fat, total fat, and cholesterol (DASH diet), during which time subjects
      remained weight stable. The main outcome measures were fasting total cholesterol,
      LDL cholesterol, HDL cholesterol, and triacylglycerol. RESULTS: Relative to the
      control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7
      mg/dL), LDL- (-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7
      mg/dL) cholesterol concentrations (all P < 0.0001), without significant effects
      on triacylglycerol. The net reductions in total and LDL cholesterol in men were
      greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by
      0.29 mmol/L, or 11.2 mg/dL (P < 0.02), respectively. Changes in lipids did not
      differ significantly by race or baseline lipid concentrations, except for HDL,
      which decreased more in participants with higher baseline HDL-cholesterol
      concentrations than in those with lower baseline HDL-cholesterol concentrations.
      The fruit and vegetable diet produced few significant lipid changes. CONCLUSIONS:
      The DASH diet is likely to reduce coronary heart disease risk. The possible
      opposing effect on coronary heart disease risk of HDL reduction needs further
      study.

PMID- 11451722
TI  - Ethnic differences in dietary intakes, physical activity, and energy expenditure
      in middle-aged, premenopausal women: the Healthy Transitions Study.
AB  - BACKGROUND: Menopause is a time of increased risk of obesity in women. The effect
      of menopause in African American women, in whom obesity is already highly
      prevalent, is unknown. OBJECTIVE: We compared dietary intakes and energy
      expenditure (EE) between middle-aged, premenopausal African American and white
      women participating in a longitudinal study of the menopausal transition. DESIGN:
      Dietary intakes by food record, EE by triaxial accelerometer, physical activity
      by self-report, and body composition by dual-energy X-ray absorptiometry were
      compared in 97 white and 52 African American women. Twenty-four-hour and sleeping
      EE were measured by whole-room indirect calorimetry in 56 women. RESULTS:
      Sleeping EE (adjusted for lean and fat mass) was lower in African American than
      in white women (5749 +/- 155 compared with 6176 +/- 75 kJ/d; P = 0.02); however,
      there was no significant difference in 24-h EE between groups. Reported leisure
      activity over the course of a week was less in African American than in white
      women (556 +/- 155 compared with 1079 +/- 100 kJ/d; P = 0.02), as were the daily
      hours spent standing and climbing stairs. Dietary intakes of protein, fiber,
      calcium, magnesium, and several fatty acids were significantly less in African
      Americans, whereas there were no observed ethnic differences in intakes of fat or
      carbohydrate. Body fat within the whole group was positively correlated with
      total, saturated, and monounsaturated fat intakes and inversely associated with
      fiber and calcium intakes. Fiber was the strongest single predictor of fatness.
      CONCLUSION: Ethnic differences in EE and the intake of certain nutrients may
      influence the effect of menopausal transition on obesity in African American
      women.

PMID- 11451723
TI  - Inconsistency between glycemic and insulinemic responses to regular and fermented
      milk products.
AB  - BACKGROUND: Foods with a low glycemic index are increasingly being acknowledged
      as beneficial in relation to the insulin resistance syndrome. Certain organic
      acids can lower the glycemic index of bread products. However, the possible
      effect of acids in fermented milk products on the glycemic index and on
      insulinemic characteristics has not been addressed. The metabolic effects of
      fermented milk or pickled products used as additives to mixed meals have also not
      been addressed. OBJECTIVES: One objective was to characterize the glycemic and
      insulinemic responses after intake of regular or fermented milk products (study
      1). In addition, the acute metabolic effect of fermented milk (yogurt) and
      pickled cucumber as supplements to a traditional breakfast based on a high
      glycemic index bread was evaluated (study 2). DESIGN: Ten healthy volunteers were
      served different breakfast meals after an overnight fast. Capillary blood samples
      were collected before and during 2 (study 1) or 3 (study 2) h after the meal.
      White-wheat bread was used as a reference meal in both studies. RESULTS: The
      lactic acid in the fermented milk products did not lower the glycemic and
      insulinemic indexes. Despite low glycemic indexes of 15-30, all of the milk
      products produced high insulinemic indexes of 90-98, which were not significantly
      different from the insulinemic index of the reference bread. Addition of
      fermented milk (yogurt) and pickled cucumber to a breakfast with a high-glycemic
      index bread significantly lowered postprandial glycemia and insulinemia compared
      with the reference meal. In contrast, addition of regular milk and fresh cucumber
      had no favorable effect on the metabolic responses. CONCLUSIONS: Milk products
      appear insulinotropic as judged from 3-fold to 6-fold higher insulinemic indexes
      than expected from the corresponding glycemic indexes. The presence of organic
      acids may counteract the insulinotropic effect of milk in mixed meals.

PMID- 11451724
TI  - Standard definitions of overweight and central adiposity for determining diabetes
      risk in Japanese Americans.
AB  - BACKGROUND: Despite having lower average body mass indexes (BMIs) than do whites,
      Asians are at high risk of type 2 diabetes, possibly because of their greater
      central adiposity. The criteria for identifying individuals at risk of obesity
      related conditions are usually not population specific. OBJECTIVE: Our goal was
      to determine whether the National Heart, Lung, and Blood Institute (NHLBI)
      overweight and obesity guidelines are useful for identifying diabetes risk in
      Japanese Americans. DESIGN: This was a prospective, cohort study of 466
      nondiabetic Japanese Americans [age: 52.2 +/- 0.6 y; BMI (in kg/m(2)): 24.1 +/-
      0.2; +/- SEM]. Diabetes status at a 5-y follow-up visit was assessed with an oral
      glucose-tolerance test. RESULTS: Among 240 subjects aged < or = 55 y, incident
      diabetes was strongly associated with overweight (BMI > or = 25) at baseline
      [relative risk (RR): 22.4; 95% CI: 2.7, 183; adjusted for age, sex, smoking, and
      family history] and weight gain of > 10 kg since the age of 20 y (adjusted RR:
      4.5; 95% CI: 1.4, 14.5). NHLBI definitions of central obesity (waist
      circumference > or = 88 cm for women and > or = 102 cm for men) were unsuitable
      for this population because only 15 of 240 subjects met these criteria. A waist
      circumference greater than or equal to the third tertile was associated with
      diabetes (adjusted RR: 5.4; 95% CI: 1.7, 17.0). Among 226 subjects aged >55 y,
      incident diabetes was not associated with BMI, weight gain, or waist
      circumference. CONCLUSIONS: NHLBI definitions are useful for identifying
      overweight Japanese Americans aged < 55 y who are at high risk of diabetes.
      Although central adiposity is an important risk factor, the guidelines for waist
      circumference are insensitive predictors of diabetes risk in this population.

PMID- 11451725
TI  - Concomitant supplemental vitamin A enhances the response to weekly supplemental
      iron and folic acid in anemic teenagers in urban Bangladesh.
AB  - BACKGROUND: Iron deficiency is the most common micronutrient deficiency and
      affects >2 billion persons worldwide, leading to anemia in >40% of women of
      reproductive age in the developing world. OBJECTIVE: The objective was to
      determine whether weekly supplementation with iron and folate would reduce the
      frequency of anemia in teenage women in urban Bangladesh before they became
      pregnant. DESIGN: Participants with a hemoglobin concentration of 80-120 g/L were
      entered into a randomized, double-blind, placebo-controlled trial and received
      supplements of placebo, vitamin A, iron + folic acid, or iron + folic acid +
      vitamin A weekly for 12 wk. The supplements contained 2.42 mg vitamin A (retinol)
      as retinyl palmitate, 120 mg elemental Fe as ferrous sulfate, and 3.5 mg folic
      acid. RESULTS: Hemoglobin concentrations increased significantly more after
      supplementation with iron + folic acid or iron + folic acid + vitamin A than
      after either the placebo or vitamin A alone. There was a significantly greater
      increase in hemoglobin after iron + folic acid + vitamin A than after iron +
      folic acid, but the additional effect disappeared after adjustment for baseline
      hemoglobin, serum vitamin A, and ferritin and the number of supplements taken.
      Those with the lowest baseline hemoglobin had the greatest increase in
      hemoglobin. Compared with the placebo, iron + folic acid + vitamin A reduced
      anemia by 92%, iron deficiency by 90%, and vitamin A deficiency by 76%.
      CONCLUSION: There may be significant health benefits from a program that enhances
      the nutritional status of iron, folate, and vitamin A in poor urban young women
      before they become pregnant.

PMID- 11451726
TI  - Effect of acute zinc depletion on zinc homeostasis and plasma zinc kinetics in
      men.
AB  - BACKGROUND: Zinc homeostasis and normal plasma zinc concentrations are maintained
      over a wide range of intakes. OBJECTIVE: The objective was to identify the
      homeostatic response to severe zinc depletion by using compartmental analysis.
      DESIGN: Stable zinc isotope tracers were administered intravenously to 5 men at
      baseline (12.2 mg dietary Zn/d) and after 5 wk of acute zinc depletion (0.23
      mg/d). Compartmental modeling of zinc metabolism was performed by using tracer
      and mass data in plasma, urine, and feces collected over 6-14 d. RESULTS: The
      plasma zinc concentration fell 65% on average after 5 wk of zinc depletion. The
      model predicted that fractional zinc absorption increased from 26% to essentially
      100%. The rate constants for zinc excretion in the urine and gastrointestinal
      tract decreased 96% and 74%, respectively. The rate constants describing the
      distribution kinetics of plasma zinc did not change significantly. When zinc
      depletion was simulated by using an average mass model of zinc metabolism at
      baseline, the only change that accounted for the observed fall in plasma zinc
      concentration was a 60% reduction in the rate constant for zinc release from the
      most slowly turning over zinc pool. The large changes in zinc intake, excretion,
      and absorption-even when considered together-only explained modest reductions in
      plasma zinc mass. CONCLUSION: The kinetic analysis with a compartmental model
      suggests that the profound decrease in plasma zinc concentrations after 5 wk of
      severe zinc depletion was mainly due to a decrease in the rate of zinc release
      from the most slowly turning over body zinc pool.

PMID- 11451727
TI  - Folic acid enrichment of bread does not appear to affect zinc absorption in young
      women.
AB  - BACKGROUND: In several countries cereals are now enriched with folic acid to
      reduce the risk of neural tube defects. Human studies suggest that folic acid
      interferes with zinc absorption. This raises concerns about the zinc status of
      high-risk groups such as infants, pregnant women, and older persons. OBJECTIVE:
      We sought to determine the effect of added folic acid on zinc absorption from
      white bread with high and low zinc contents. DESIGN: Zinc absorption was measured
      in 15 healthy women (22-33 y), each of whom consumed 4 single meals spaced 2 wk
      apart in a randomized crossover design. The servings of bread (100 g) differed in
      zinc and folic acid contents as follows: A, 1.2 mg Zn and 17 microg folic acid;
      B, 1.2 mg Zn and 144 microg folic acid; C, 3.0 mg Zn and 17 microg folic acid;
      and D, 2.9 mg Zn and 144 microg folic acid. Meals were extrinsically labeled with
      65Zn and absorption was estimated from whole-body retention measurements. Folate
      status was assessed by measuring plasma and erythrocyte folate and plasma
      homocysteine concentrations. RESULTS: Mean (+/-SD) zinc absorption did not differ
      significantly in relation to the folate content of the breads at either the low
      zinc content (38.8 +/- 13.5% and 40.6 +/- 16.5% for A and B, respectively; P =
      0.74) or the high zinc content (26.7 +/- 9.3% and 22.7 +/- 6.6% for C and D,
      respectively; P = 0.16). There was no significant correlation between folate
      status and zinc absorption (r < 0.3, P > 0.1). CONCLUSION: Fortification of white
      bread with a commonly used amount of folic acid did not appear to influence zinc
      absorption at either a high or a low zinc content.

PMID- 11451728
TI  - Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the
      Hordaland Homocysteine Study.
AB  - BACKGROUND: Few population-based studies have assessed relations between plasma
      or serum total homocysteine (tHcy) and all-cause mortality. OBJECTIVE: Our goal
      was to study associations between plasma tHcy and all-cause, cardiovascular, and
      noncardiovascular mortality. DESIGN: This was a prospective cohort study of 2127
      men and 2639 women aged 65-67 y in 1992-1993 when they were recruited as part of
      a population-based national cardiovascular screening program carried out in
      Hordaland County, Norway. RESULTS: During a median of 4.1 y of follow-up, 162 men
      and 97 women died. A strong relation was found between plasma tHcy and all-cause
      mortality. The association was highly significant for noncardiovascular and for
      cardiovascular causes of death. In a comparison of individuals having tHcy
      concentrations of 9.0-11.9, 12.0-14.9, 15.0-19.9, or > or = 20 micromol/L with
      individuals having a tHcy concentration < 9 micromol/L, adjusted mortality ratios
      were 1.4, 1.9, 2.3, and 3.6 (P for trend = 0.0002) for noncardiovascular and 1.3,
      2.1, 2.6, and 3.5 (P for trend = 0.0002) for cardiovascular causes of death. A
      tHcy increment of 5 micromol/L was associated with a 49% (95% CI: 28%, 72%)
      increase in all-cause mortality, a 50% (95% CI: 21%, 85%) increase in
      cardiovascular mortality (121 deaths), a 26% (95% CI: -2%, 63%) increase in
      cancer mortality (103 deaths), and a 104% (95% CI: 44%, 289%) increase in
      noncancer, noncardiovascular mortality (33 deaths). CONCLUSION: Plasma tHcy is a
      strong predictor of both cardiovascular and noncardiovascular mortality in a
      general population of 65-72-y-olds. These results should encourage studies of
      tHcy in a wider perspective than one confined to cardiovascular disease.

PMID- 11451729
TI  - Immunologic evidence of no harmful effect of oats in celiac disease.
AB  - BACKGROUND: It was recently shown that antiendomysial antibodies (EMAs), which
      are highly sensitive and specific for celiac disease, are produced by intestinal
      mucosa. Furthermore, EMAs were detected previously in supernatant fluid from
      cultured duodenal mucosa specimens collected from untreated celiac disease
      patients and in culture media of biopsy specimens collected from treated celiac
      disease patients after an in vitro challenge with gliadin. Moreover, it was
      recently shown in vivo that oats are not toxic to celiac disease patients,
      suggesting the safety of oats in a gluten free-diet. OBJECTIVE: The objective was
      to better define the controversial role of oats in celiac disease to determine
      whether oats can be safely included in a gluten-free diet. DESIGN: We used an in
      vitro model to test whether oats induce EMA production in supernatant fluid from
      cultured duodenal mucosa specimens collected from 13 treated celiac disease
      patients. The biopsy specimens were cultured with and without peptic-tryptic
      digest (PT) of gliadin and avenin (from oats) and in medium alone. Samples from 5
      of the 13 patients were cultured with the C fraction of PT-avenin. Indirect
      immunofluorescence was used to detect EMAs. RESULTS: EMAs were detected in
      specimens from all 13 patients after the challenge with gliadin but not after
      culture in medium alone. By contrast, no EMAs were detected in any of the
      specimens cultured with PT-avenin and its C fraction. CONCLUSIONS: Because the in
      vitro challenge with PT-avenin and its C fraction did not induce EMA production
      in treated celiac disease patients, it appears that oats have no harmful effect
      on celiac disease. Therefore, oats can be safely included in a gluten-free diet.

PMID- 11451730
TI  - Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study
      on Diet and Cancer.
AB  - BACKGROUND: Plant sterols in vegetable foods might prevent colorectal cancer.
      OBJECTIVE: The objective was to study plant sterol intakes in relation to
      colorectal cancer risk in an epidemiologic study. DESIGN: The study was performed
      within the framework of the Netherlands Cohort Study on Diet and Cancer in 120852
      subjects who completed a baseline questionnaire in 1986. After 6.3 y of follow
      up, 620 colon and 344 rectal cancer cases were detected. A case-cohort approach
      was used to calculate confounder-adjusted rate ratios (RRs) and their 95% CIs for
      quintiles of plant sterol intake. RESULTS: The total mean (+/-SD) intake of
      campesterol, stigmasterol, beta-sitosterol, campestanol, and beta-sitostanol was
      285 +/- 97 mg/d. Major contributors to plant sterol intake were bread (38%),
      vegetable fats (26%), and fruit and vegetables (21%). For men, there was no clear
      association between intake of any of the plant sterols and colon cancer risk when
      age, smoking, alcohol use, family history of colorectal cancer, education level,
      and cholecystectomy were controlled for. Adjustment for energy did not alter the
      result. For rectal cancer, adjustment for energy resulted in positive
      associations between risk and campesterol and stigmasterol intakes. For women,
      there was no clear association between intake of any of the plant sterols and
      colorectal cancer risk. CONCLUSION: A high dietary intake of plant sterols was
      not associated with a lower risk of colon and rectal cancers in the Netherlands
      Cohort Study on Diet and Cancer.

PMID- 11451731
TI  - Tracking of body mass index from childhood to adolescence: a 6-y follow-up study
      in China.

PMID- 11451734
TI  - Mechanism of action and pharmacology of unfractionated heparin.

PMID- 11451735
TI  - Does exercise increase HDL cholesterol in those who need it the most?

PMID- 11451736
TI  - Plaque T-cell activity: not so specific?

PMID- 11451737
TI  - Gene-environment interaction in the expression of antioxidant status: a role for
      genes in the relationship between smoking and coronary disease.

PMID- 11451738
TI  - Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in
      angiogenesis.
AB  - Extracellular proteolysis is an absolute requirement for new blood vessel
      formation (angiogenesis). This review examines the role of the matrix
      metalloproteinase (MMP) and plasminogen activator (PA)-plasmin systems during
      angiogenesis. Specifically, a role for gelatinases (MMP-2, MMP-9), membrane-type
      1 MMP (MMP-14), the urokinase-type PA receptor, and PA inhibitor 1 has been
      clearly defined in a number of model systems. The MMP and PA-plasmin systems have
      also been implicated in experimental vascular tumor formation, and their role
      during this process will be examined. Antiproteolysis, particularly in the
      context of angiogenesis, has become a key target in therapeutic strategies aimed
      at inhibiting tumor growth and other diseases associated with neovascularization.

PMID- 11451739
TI  - Phenotypic heterogeneity influences apoptotic susceptibility to retinoic acid and
      cis-platinum of rat arterial smooth muscle cells in vitro: Implications for the
      evolution of experimental intimal thickening.
AB  - Rat aortic smooth muscle cells (SMCs) cultured from intimal thickening 15 days
      after endothelial injury (IT-15), unlike those of normal media, show a
      monolayered, epithelioid phenotype and high levels of cellular retinol binding
      protein-1 (CRBP). Epithelioid clones obtained from the normal media suggest a
      "mosaicism" of arterial SMCs. Intimal cell homeostasis from the balance of
      proliferation and apoptosis is critical for the progression of vascular lesions.
      All-trans retinoic acid (tRA) reduced [(3)H]thymidine incorporation and G(1)-->S
      phase progression of IT-15 and epithelioid clone but not of normal media and IT
      60 days after injury (IT-60) SMCs. Hoechst staining, flow cytometry, and ligation
      mediated polymerase chain reaction showed an increased susceptibility of IT-15
      and epithelioid clone to tRA and cis-diaminedichloroplatinum II (CDDP)-induced
      apoptosis and cytotoxicity compared with normal media and IT-60 cells. The latter
      retained an increased susceptibility to tRA-induced apoptosis compared with
      normal media SMCs. tRA-induced apoptosis associated with an increased ratio of
      bax to bcl-2 by bax overexpression and cleavage of caspase-3. Anti-CRBP but not
      anti-IgG antibody prevented tRA-induced apoptosis and changes in related
      signaling molecules but not CDDP effects. Our findings support the relevant role
      of phenotypic heterogeneity in the determining proliferative as well as apoptotic
      behavior of arterial SMCs.

PMID- 11451740
TI  - Apoptotic death of inflammatory cells in human atheroma.
AB  - Although the accumulation of cholesterol and other lipidic material is
      unquestionably important in atherogenesis, the reasons why this material
      progressively accumulates, rather than being effectively cleared by phagocytic
      cells such as macrophages, are not completely understood. We hypothesize that
      atheromatous lesions may represent "death zones" that contain toxic materials
      such as oxysterols and in which monocytes/macrophages become dysfunctional and
      apoptotic. Indeed, cathepsins B and L, normally confined to the lysosomal
      compartment, are present in the cytoplasm and nuclei of apoptotic (caspase-3
      positive) macrophages within human atheroma. The possible involvement of
      oxysterols is suggested by experiments in which cultured U937 and THP-1 cells
      exposed to 7-oxysterols similarly undergo marked lysosomal destabilization,
      caspase-3 activation, and apoptosis. Like macrophages within atheroma,
      intralysosomal cathepsins B and L are normally present in the cytoplasm and
      nuclei of these oxysterol-exposed cells. Lysosomal destabilization, cathepsin
      release, and apoptosis may be causally related, because inhibitors of cathepsins
      B and L suppress oxysterol-induced apoptosis. Thus, toxic materials such as 7
      oxysterols in atheroma may impair the clearance of cholesterol and other lipidic
      material by fostering the apoptotic death of phagocytic cells, thereby
      contributing to further development of atherosclerotic lesions.

PMID- 11451741
TI  - Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation
      and oxidized LDL-induced apoptosis in mouse aortic cells.
AB  - Transgenic mice overexpressing Cu/Zn superoxide dismutase (hSod1Tg(+/0)) or
      catalase (hCatTg(+/0)) and knockout mice underexpressing manganese superoxide
      dismutase (Sod2(+/)(-)) or glutathione peroxidase-1 (Gpx1(-/-)) were used to
      study the effect of antioxidant enzymes on cell-mediated low density lipoprotein
      (LDL) oxidation and oxidized LDL (oxLDL)-induced apoptosis. Incubation of LDL
      with mouse aortic segments or smooth muscle cells (SMCs) resulted in a
      significant increase in LDL oxidation. However, LDL oxidation was significantly
      reduced when LDL was incubated with aortic segments and SMCs obtained from
      hSod1Tg(+/0) and hCatTg(+/0) mice compared with those obtained from wild-type
      mice. In contrast, LDL oxidation was significantly increased when LDL was
      incubated with aortic segments and SMCs obtained from Sod2(+/)(-) and Gpx1(-/-)
      mice. CuSO(4)-oxidized LDL increased DNA fragmentation and caspase activities in
      the primary cultures of mouse aortic SMCs. However, oxLDL-induced DNA
      fragmentation and caspase activities were reduced 50% in SMCs obtained from
      hSod1Tg(+/0) and hCatTg(+/0) mice compared with wild-type control mice. In
      contrast, oxLDL-induced DNA fragmentation and caspase activities were
      significantly increased in SMCs obtained from Sod2(+/)(-) and Gpx1(-/-) mice.
      These findings suggest that overexpression of Cu/Zn superoxide dismutase or
      catalase reduces cell-mediated LDL oxidation and oxLDL-induced apoptosis, whereas
      underexpression of manganese superoxide dismutase or glutathione peroxidase-1
      increases cell-mediated LDL oxidation and oxLDL-induced apoptosis.

PMID- 11451742
TI  - Blood flow decrease induces apoptosis of endothelial cells in previously dilated
      arteries resulting from chronic high blood flow.
AB  - We investigated apoptosis of endothelial cells during the arterial narrowing
      process in response to reduction in flow. The decrease in flow was created in the
      carotid artery by closure of an arteriovenous fistula (AVF), which had been
      established for 28 days in rabbits. The endothelial cell apoptosis in the carotid
      artery was studied at 1, 3, 7, and 21 days of flow reduction after closure of the
      AVF by use of terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) with laser scanning confocal microscopy and transmission and
      scanning electron microscopy. After AVF closure, arterial lumen diameter was
      reduced by 36%, and compared with endothelial cells before the closure, the
      number of endothelial cells was decreased by 45% at 21 days. Endothelial cell
      apoptosis was observed at 1 day, peaked at 3 days (381.3+/-87.1 cells per square
      millimeter), and decreased at 7 days. These cells had irregular protrusions under
      scanning electron microscopy and were characterized by fragmented nuclei under
      transmission electron microscopy. Apoptotic cells were mainly beneath the
      endothelium and were occasionally within smooth muscle cells and endothelial
      cells. The results suggest that apoptosis of endothelial cells may play a role in
      the arterial remodeling in response to a reduction in flow.

PMID- 11451743
TI  - Injury induces dedifferentiation of smooth muscle cells and increased matrix
      degrading metalloproteinase activity in human saphenous vein.
AB  - Long-term patency of human saphenous vein bypass grafts is low because of intimal
      thickening and superimposed atherosclerosis. Matrix-degrading metalloproteinases
      (MMPs) and changes in vascular smooth muscle cell (VSMC) phenotype are thought to
      be essential for the VSMC migration that contributes to intimal thickening. We
      examined VSMC phenotype and MMP activity in saphenous veins obtained before and
      after surgical manipulation. Surgical preparation of the veins significantly
      increased pro-MMP-1 expression by 2-fold and significantly reduced tissue
      inhibitor of MMPs (TIMP)-2 expression, whereas MMP-3 and TIMP-1 were unaffected.
      Furthermore, caseinolytic and gelatinolytic activities measured by in situ
      zymography were dramatically elevated by injury. The expression of desmin and
      smoothelin was significantly decreased by injury, whereas vimentin expression was
      significantly increased. In addition, these changes in phenotype and MMP activity
      were localized to a subpopulation of VSMCs, the circumferential medial VSMCs. Our
      data show that surgical preparative injury induces phenotypic modulation of a
      subpopulation of medial VSMCs to a synthetic phenotype and increases MMP
      activity. This may favor matrix degradation, VSMC migration, and the subsequent
      intimal thickening that leads to graft failure.

PMID- 11451744
TI  - Cell cycle protein expression in vascular smooth muscle cells in vitro and in
      vivo is regulated through phosphatidylinositol 3-kinase and mammalian target of
      rapamycin.
AB  - Cell cycle progression represents a key event in vascular proliferative diseases,
      one that depends on an increased rate of protein synthesis. An increase in
      phosphatidylinositol 3-kinase (PI 3-kinase) activity is associated with vascular
      smooth muscle cell proliferation, and rapamycin, which blocks the activity of the
      mammalian target of rapamycin, inhibits this proliferation in vitro and in vivo.
      We hypothesized that these 2 molecules converge on a critical pathway of
      translational regulation that is essential for successful upregulation of cell
      cycle-regulatory proteins in activated smooth muscle cells. p70(S6) kinase, a
      target of PI 3-kinase and the mammalian target of rapamycin, was rapidly
      activated on growth factor stimulation of quiescent coronary artery smooth muscle
      cells and after balloon injury of rat carotid arteries. The translational
      repressor protein 4E-binding protein 1 was similarly hyperphosphorylated under
      these conditions. These events were associated with increases in the protein
      levels of cyclin B1, cyclin D1, cyclin E, cyclin-dependent kinase 1, cyclin
      dependent kinase 2, proliferating cell nuclear antigen, and p21(Cip1) in vivo and
      in vitro, whereas inhibition of the PI 3-kinase signaling pathway with either
      rapamycin or wortmannin blocked the upregulation of these cell cycle proteins,
      but not mRNA, and arrested the cells in vitro before S phase. In contrast to
      findings in other cell types, growth factor- or balloon injury-induced
      downregulation of the cell cycle inhibitor p27(Kip1) was not affected by
      rapamycin treatment. These data suggest that cell cycle progression in vascular
      cells in vitro and in vivo depends on the integrity of the PI 3-kinase signaling
      pathway in allowing posttranscriptional accumulation of cell cycle proteins.

PMID- 11451745
TI  - LDL-activated p38 in endothelial cells is mediated by Ras.
AB  - Endothelial dysfunction is a major atherogenic proinflammatory event. LDL causes
      the activation and phenotypic changes of cultured vascular endothelial cells
      (ECs). We previously reported that LDL activates c-Jun and AP-1 in ECs. In this
      study, we demonstrated that p38-ATF-2 is activated by LDL in human ECs and that
      this activation is mediated by Ras. When ECs are incubated with LDL in
      pathophysiological concentrations, the p38-mediated ATF-2 phosphorylation and ATF
      2 transactivation are increased in a time- and dose-dependent manner. To
      elucidate the upstream mechanism in LDL-activated p38 in ECs, we demonstrate that
      LDL increases Ras translocation from the cytoplasm to the cellular membrane, with
      concurrent increases in Ras binding activity to GST-Raf-1. Overexpression of
      RasN17, a dominant negative mutant of Ras, attenuates the LDL-induced increases
      in (1) phosphorylation of ATF-2, (2) phosphorylation of c-Jun, (3) AP-1 binding,
      and (4) AP-1-driven luciferase activity. To study the effect of p38 in the
      regulation of an LDL targeting gene, we show that a specific p38 inhibitor
      attenuates LDL-induced E-selectin at the mRNA level. Thus, LDL activates both p38
      and JNK signaling pathways through Ras activation, and furthermore, these events
      may play an important role in LDL-induced endothelial activation.

PMID- 11451746
TI  - Hmg-CoA reductase inhibitor modulates monocyte-endothelial cell interaction under
      physiological flow conditions in vitro: involvement of Rho GTPase-dependent
      mechanism.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been
      reported to exert actions independent of their lipid-lowering effects. To
      critically assess the effects of statins on monocyte-endothelial cell
      interactions, we used an in vitro model that mimicked physiological flow
      conditions. Monocytic U937 cells were incubated in the presence of cerivastatin
      for 48 hours. Adhesive interactions of statin-treated U937 cells were then
      analyzed by use of activated (interleukin-1beta 10 U/mL, 4 hours) human umbilical
      vein endothelial cells in an in vitro flow apparatus. Flow cytometric analysis of
      adhesion molecules and measurement of F-actin content in U937 cells were
      performed before and after statin treatment. Preincubation with cerivastatin
      significantly decreased U937 firm adhesion to activated human umbilical vein
      endothelial cells, whereas U937 rolling was not decreased. Fluorescence-activated
      cell sorter analysis revealed downregulation of U937 surface expression of CD11a,
      CD18, and VLA4 after statin treatment. Cerivastatin significantly reduced F-actin
      content in U937 cells and inhibited RhoA translocation, whereas preincubation
      with C3 exoenzyme reduced U937 adhesion under flow. Cerivastatin reduces monocyte
      adhesion to vascular endothelium under physiological flow conditions via
      downregulation of integrin adhesion molecules and inhibition of actin
      polymerization via RhoA inactivation. Our findings have important implications
      for the lipid-independent effects of statins.

PMID- 11451747
TI  - Tranilast inhibits cardiac allograft vasculopathy in association with
      p21(Waf1/Cip1) expression on neointimal cells in murine cardiac transplantation
      model.
AB  - Cardiac allograft vasculopathy is a major complication after cardiac
      transplantation, often limiting long-term recipient survival. N-(3,4
      Dimethoxycinnamoyl)anthranilic acid (tranilast) inhibits cyclin-dependent kinase
      activity through p21(Waf1/Cip1) induction and arrests vascular smooth muscle cell
      proliferation in vitro. We tested a hypothesis that tranilast inhibits the
      vasculopathy characterized by diffuse intimal thickening in a murine heart
      transplantation model. Hearts from DBA/2 mice were heterotopically transplanted
      into B10.D2 mice as allografts. Oral administration of tranilast started 3 days
      before transplantation at doses of 550 or 1040 mg/kg per day until the animals
      were killed. Cardiac allograft vasculopathy was defined as luminal stenosis
      caused by neointimal formation. The percentage of luminal stenosis and cardiac
      rejection were analyzed 14 and 28 days after transplantation. Tranilast
      administration was associated with a marked reduction in luminal occlusion but
      with no significant effect on cardiac rejection. Immunohistochemical study of the
      tranilast-treated graft coronary arteries revealed enhancement of p21(Waf1/Cip1)
      and decreased expression of proliferating cell nuclear antigen in the neointima.
      The significant reduction in allograft vasculopathy concomitant with the
      enhancement of p21(Waf1/Cip1) indicates that tranilast has an antiproliferative
      effect that could be applicable to clinical treatment of cardiac allograft
      vasculopathy.

PMID- 11451748
TI  - 4-hydroxynonenal prevents NO production in vascular smooth muscle cells by
      inhibiting nuclear factor-kappaB-dependent transcriptional activation of
      inducible NO synthase.
AB  - The role of lipid peroxidation products in atherogenesis was studied. We
      investigated whether 4-hydroxy-2-nonenal (HNE) modulates activation of the
      nuclear factor (NF)-kappaB system or alters expression of the NF-kappaB target
      gene product, inducible NO synthase (iNOS), in vascular smooth muscle cells
      (VSMCs) stimulated by lipopolysaccharide (LPS) in combination with interferon
      (IFN)-gamma (LPS/IFN). NO production induced by LPS/IFN was dose-dependently
      inhibited by HNE. NF-kappaB activation by LPS/IFN was inhibited by HNE in a dose
      dependent manner. HNE significantly decreased LPS/IFN-stimulated proteolysis of
      IkappaB-alpha. iNOS promoter activity stimulated by LPS/IFN was also decreased by
      HNE dose-dependently. The treatment of VSMCs with LPS/IFN strongly stimulated
      iNOS mRNA and protein expression. The LPS/IFN-induced increases in iNOS mRNA and
      protein levels were dose-dependently decreased by HNE. Our data suggest that
      treatment with HNE blocks signaling events required for IkappaB-alpha
      degradation, thereby preventing NF-kappaB activation. Inhibition of NF-kappaB
      regulated gene expression, especially modulation of NO production, may contribute
      to atherogenesis.

PMID- 11451749
TI  - Aortic wall mechanics and composition in a transgenic mouse model of Marfan
      syndrome.
AB  - In Marfan syndrome, mutations of the fibrillin gene (FBN1) lead to aneurysm of
      the thoracic aorta, making the aortic wall more susceptible to dissection, but
      the precise sequence of events underlying aneurysm formation is unknown. We used
      a rodent model of Marfan syndrome, the mgR/mgR mouse (with mgR: hypomorphic FBN1
      mutation), which underexpresses FBN1, to distinguish between a defect in the
      early formation of elastic fibers and the later disruption of elastic fibers. The
      content of desmosine plus isodesmosine was used as an index of early
      elastogenesis; disruption of elastic fibers was analyzed by histomorphometry.
      Because disruption of the medial elastic fibers may produce aortic stiffening, so
      amplifying the aneurysmal process, we measured thoracoabdominal pulse wave
      velocity as an indicator of aortic wall stiffness. Both mgR/mgR and wild-type
      (C57BL/6J-129SV) strains were normotensive, and wall stress was not significantly
      modified because the increase in internal diameter (0.80+/-0.06 vs 0.63+/-0.03 mm
      in wild type, P<0.05) was accompanied by increased medial cross-sectional area.
      The aortic wall stiffened (4-fold increase in the elastic modulus-to-wall stress
      ratio). Desmosine content was not modified (mgR/mgR 432+/-31 vs wild type 492+/
      42 microg/mg wet weight, P>0.05). Elastic fibers showed severe fragmentation: the
      percentage of the media occupied by elastic fibers was 18+/-3% in mgR/mgR mice vs
      30+/-1% in wild-type mice, with the number of elastic segments being 1.9+/-0.2 vs
      1.4+/-0.1x10(-6)/mm(2) in the wild type (both P<0.05). In conclusion,
      underexpression of FBN1 in mice leads to severe elastic network fragmentation but
      no change in cross-linking, together with aortic dilatation. This result suggests
      that fragmentation of the medial elastic network and not a defect in early
      elastogenesis is 1 of the determinants of aortic dilatation in Marfan syndrome.

PMID- 11451750
TI  - Genetic contributions to plasma total antioxidant activity.
AB  - Oxidative stress plays important roles in a wide spectrum of pathological
      processes, such as atherosclerosis. Although several environmental factors are
      documented to influence redox metabolism, relatively little is known about
      genetic effects. In the present study, we evaluated genetic contributions to
      variation in plasma total antioxidant status (TAS), a measure of peroxyl
      scavenging capacity, in 1337 members of 40 Mexican American families. TAS levels
      were significantly lower in women than in men (1.675+/-0.004 versus 1.805+/-0.005
      mmol/L, respectively; P<0.001), and there was a significant decline of TAS levels
      with age in men but not in women (P<0.01 for the interaction). Quantitative
      genetic analysis indicated the heritability of TAS levels to be 0.509+/-0.052;
      ie, approximately 51% of the residual variance (after covariate adjustment) in
      TAS levels was due to the additive effects of genes (P<0.001). We have further
      observed a significant gene-by-smoking interaction (P<0.05). Additive genetic
      effects account for 83% of the residual phenotypic variance in TAS levels among
      smokers, but they account for only 49% in nonsmokers. However, genes contributing
      to TAS variation are the same in smokers and nonsmokers. Our study for the first
      time demonstrates that TAS, an indicator of redox homeostasis, is under strong
      genetic control, especially among smokers. With appropriate tools, such as genome
      screening, it should be possible to localize genes that regulate redox
      homeostasis and, ultimately, identify the DNA sequence variants predisposing
      subjects to oxidative damage.

PMID- 11451751
TI  - Folate improves endothelial function in coronary artery disease: an effect
      mediated by reduction of intracellular superoxide?
AB  - Homocysteine is a risk factor for coronary artery disease (CAD). Folic acid
      lowers homocysteine and may improve endothelial function in CAD, although the
      mechanism is unclear. We investigated the effect of folic acid on endothelial
      function, homocysteine, and oxidative stress in patients with CAD. We also
      examined the acute effect of 5-methyltetrahydrofolate (5-MTHF), the principal
      circulating folate, on endothelial function in vivo and on intracellular
      superoxide in cultured endothelial cells. A randomized crossover study of folic
      acid (5 mg daily) for 6 weeks was undertaken in 52 patients with CAD. Ten further
      patients were given intra-arterial 5-MTHF. Endothelial function was assessed by
      flow-mediated dilatation (FMD). Folic acid increased plasma folate (P<0.001),
      lowered homocysteine by 19% (P<0.001), and improved FMD (P<0.001). FMD
      improvement did not correlate with homocysteine reduction. Malondialdehyde and
      total plasma antioxidant capacity, markers of oxidative stress, were unchanged. 5
      MTHF acutely improved FMD (P<0.001) without altering homocysteine (P=0.47). In
      vitro, 5-MTHF abolished homocysteine-induced intracellular superoxide increase
      (P<0.001); this effect was also observed with folic acid and tetrahydrobiopterin.
      Our data support the beneficial effect of folic acid on endothelial function in
      CAD but suggest that the mechanism is independent of homocysteine. Reduction of
      intracellular endothelial superoxide may have contributed to the effect.

PMID- 11451752
TI  - Aortic aneurysm diameter and risk of cardiovascular mortality.
AB  - After successful surgical repair of an abdominal aortic aneurysm, patients have
      for many years an increased risk of death from cardiovascular causes. We have
      tested the hypothesis that for patients with abdominal aortic aneurysms, the risk
      of nonaneurysm cardiovascular mortality before and after surgery increased with
      aneurysm diameter. Records of aneurysm repair or rupture and mortality were
      available from 2305 patients entered into the UK Small Aneurysm Trial and Study.
      Two hundred fifty-nine deaths occurred before aneurysm repair or rupture (mean
      follow-up 1.7 years), and 325 occurred after surgical repair (mean follow-up 3.6
      years). The risk of nonaneurysm-related mortality and cardiovascular death before
      and after surgery increased with aneurysm diameter at baseline, even after
      adjustment for other known risk factors. The adjusted hazard ratios for
      cardiovascular mortality, per standard deviation (0.8-cm) increase in aneurysm
      diameter, were 1.34 (95% CI 1.01 to 1.79) and 1.31 (95% CI 1.06 to 1.63) in the
      periods before aneurysm repair or rupture and after aneurysm repair,
      respectively. The significant association between aortic diameter and
      cardiovascular mortality, excluding aneurysm-related deaths, suggests that
      aneurysm diameter is an independent marker of cardiovascular disease risk.

PMID- 11451753
TI  - Interleukin-15 expression in atherosclerotic plaques: an alternative pathway for
      T-cell activation in atherosclerosis?
AB  - T-cell activation in atherosclerotic plaques is thought to be initiated by plaque
      derived antigens, such as oxidized LDL (oxLDL). An alternative pathway of T-cell
      activation independent of antigen stimulation, mediated by the cytokine
      interleukin (IL)-15, was recently described. We investigated IL-15 expression in
      atherosclerotic plaques in relation to plaque morphology, inflammatory cells, T
      cell activation, and oxidation-specific epitopes by use of immunohistochemistry.
      In situ hybridization was used to evaluate IL-15 mRNA expression. We also studied
      the proliferative response of plaque-derived T-cell lines to IL-15 in vitro using
      [(3)H]thymidine incorporation. Fresh-frozen specimens were classified as fibrous
      (n=9), fibrolipid (n=8), and lipid-rich (n=14) plaques; normal vessels (n=4)
      served as reference. Expression of IL-15 mRNA and protein was found almost solely
      in fibrolipid and lipid-rich plaques, associated with oxLDL-positive macrophages.
      Sequential immunostains revealed colocalization between IL-15- and CD40L-positive
      T cells. Moreover, plaque-derived T-cell lines were highly responsive to IL-15.
      Hence, IL-15 could provide a pathway for antigen-independent T-cell activation.

PMID- 11451754
TI  - Complement components, but not complement inhibitors, are upregulated in
      atherosclerotic plaques.
AB  - Complement activation occurs in atherosclerotic plaques. The capacity of arterial
      tissue to inhibit this activation through generation of the complement regulators
      C1 inhibitor, decay accelerating factor, membrane cofactor protein (CD46), C4
      binding protein (C4BP), and protectin (CD59) was evaluated in pairs of aortic
      atherosclerotic plaques and nearby normal artery from 11 human postmortem
      specimens. All 22 samples produced mRNAs for each of these proteins. The ratios
      of plaque versus normal artery pairs was not significantly different from unity
      for any of these inhibitors. However, in plaques, the mRNAs for C1r and C1s, the
      substrates for the C1 inhibitor, were increased 2.35- and 4.96-fold,
      respectively, compared with normal artery; mRNA for C4, the target for C4BP, was
      elevated l.34-fold; and mRNAs for C7 and C8, the targets for CD59, were elevated
      2.61- and 3.25-fold, respectively. By Western blotting and immunohistochemistry,
      fraction Bb of factor B, a marker of alternative pathway activation, was barely
      detectable in plaque and normal arterial tissue. These data indicate that it is
      primarily the classical, not the alternative pathway, that is activated in
      plaques and that key inhibitors are not upregulated to defend against this
      activation.

PMID- 11451755
TI  - Distribution of lipid deposits around aortic branches of mice lacking LDL
      receptors and apolipoprotein E.
AB  - Mice with inactivated genes are increasingly used as models of human
      atherosclerosis. The aim of the present study was to determine whether the
      characteristic age-related distributions of lipid deposition seen around human
      arterial branches are replicated in such mice. Lesions occur downstream of branch
      ostia in immature human aortas, but these regions are spared in adult vessels,
      with lesions occurring more frequently at the sides or upstream of the branches.
      We determined the pattern of lipid staining around 102 intercostal branch ostia
      from apolipoprotein E/low density lipoprotein receptor double-knockout mice aged
      9 to 20 weeks by using en face microscopy and a frequency-mapping technique.
      Lesion prevalence was high in the ostium and the region immediately surrounding
      it. Frequencies were 2.12+/-0.30 (mean+/-SEM, n=11) times higher upstream than
      downstream (P<0.01), but the pattern did not resemble the adult human pattern:
      there were no peaks in frequency at the sides or upstream of the branch, and
      there was no sparing downstream. Furthermore, a patch of sparing upstream of the
      branch was seen, which has not been reported for human vessels, and there was no
      trend toward a more upstream pattern with age. We conclude that knockout mice may
      not be a suitable model in which to investigate localizing factors.

PMID- 11451756
TI  - Effects of endurance exercise training on plasma HDL cholesterol levels depend on
      levels of triglycerides: evidence from men of the Health, Risk Factors, Exercise
      Training and Genetics (HERITAGE) Family Study.
AB  - High density lipoprotein (HDL) cholesterol concentrations have been shown to
      increase with regular endurance exercise and, therefore, can contribute to a
      lower risk of coronary heart disease in physically active individuals compared
      with sedentary subjects. Although low HDL cholesterol levels are frequently
      observed in combination with hypertriglyceridemia, some individuals may be
      characterized by isolated hypoalphalipoproteinemia, ie, low HDL cholesterol
      levels in the absence of elevated triglyceride (TG) concentrations. The present
      study compared the responses of numerous lipoprotein-lipid variables to a 20-week
      endurance exercise training program in men categorized on the basis of baseline
      TG and HDL cholesterol concentrations: (1) low TG and high HDL cholesterol
      (normolipidemia), (2) low TG and low HDL cholesterol (isolated low HDL
      cholesterol), (3) high TG and high HDL cholesterol (isolated high TGs), and (4)
      high TGs and low HDL cholesterol (high TG/low HDL cholesterol). A series of
      physical and metabolic variables was measured before and after the training
      program in a sample of 200 men enrolled in the Health, Risk Factors, Exercise
      Training and Genetics (HERITAGE) Family Study. At baseline, men with high TG/low
      HDL cholesterol had more visceral adipose tissue than did men with isolated low
      HDL cholesterol and men with normolipidemia. The 0.4% (not significant) exercise
      induced increase in HDL cholesterol levels in men with isolated low HDL
      cholesterol suggests that they did not benefit from the "HDL-raising" effect of
      exercise. In contrast, men with high TG/low HDL cholesterol showed a significant
      increase in HDL cholesterol levels (4.9%, P<0.005). Whereas both subgroups of men
      with elevated TG levels showed reductions in plasma TGs ( approximately -15.0%,
      P<0.005), only those with high TG/low HDL cholesterol showed significantly
      reduced apolipoprotein B levels at the end of the study (-6.0%, P<0.005).
      Multiple regression analyses revealed that the exercise-induced change in
      abdominal subcutaneous adipose tissue (10.6%, P<0.01) was the only significant
      correlate of the increase in plasma HDL cholesterol with training in men with
      high TG/low HDL cholesterol. Results of the present study suggest that regular
      endurance exercise training may be particularly helpful in men with low HDL
      cholesterol, elevated TGs, and abdominal obesity.

PMID- 11451757
TI  - Replacement of dietary saturated fatty acids by trans fatty acids lowers serum
      HDL cholesterol and impairs endothelial function in healthy men and women.
AB  - We tested whether trans fatty acids and saturated fatty acids had different
      effects on flow-mediated vasodilation (FMD), a risk marker of coronary heart
      disease (CHD). Consumption of trans fatty acids is related to increased risk of
      CHD, probably through effects on lipoproteins. Trans fatty acids differ from most
      saturated fatty acids because they decrease serum high-density lipoprotein (HDL)
      cholesterol, and this may increase the risk of CHD. We fed 29 volunteers 2
      controlled diets in a 2x4-week randomized crossover design. The "Trans-diet"
      contained 9.2 energy percent of trans fatty acids; these were replaced by
      saturated fatty acids in the "Sat-diet." Mean serum HDL cholesterol after the
      Trans-diet was 0.39 mmol/L (14.8 mg/dL), or 21% lower than after the Sat-diet
      (95% CI 0.28 to 0.50 mmol/L). Serum low density lipoprotein and triglyceride
      concentrations were stable. FMD+SD was 4.4+/-2.3% after the Trans-diet and 6.2+/
      3.0% after the Sat-diet (difference -1.8%, 95% CI -3.2 to -0.4). Replacement of
      dietary saturated fatty acids by trans fatty acids impaired FMD of the brachial
      artery, which suggests increased risk of CHD. Further studies are needed to test
      whether the decrease in serum HDL cholesterol caused the impairment of FMD.

PMID- 11451758
TI  - Changes in plasma triglyceride levels shift lipoprotein(a) density in parallel
      with that of LDL independently of apolipoprotein(a) size.
AB  - Lipoprotein(a) [Lp(a)] represents a class of low density lipoprotein (LDL)
      particles that have as a protein moiety apolipoprotein B-100-linked covalently to
      a single molecule of apolipoprotein(a) [apo(a)], a specific multikringle protein
      of the plasminogen family. Lp(a) is polymorphic in density because of either the
      density heterogeneity of constitutive LDL, apo(a) size, or both. Authentic LDL
      also represents a set of heterogeneous particles whose density is affected by
      metabolic events. Whether in vivo these events may also affect Lp(a) density is
      not clearly established. To this effect, we studied 75 subjects with plasma Lp(a)
      protein levels between 7 and 50 mg/dL and containing a single apo(a) size
      isoform. We used density gradient ultracentrifugation to simultaneously monitor
      the changes in the peak density of LDL and Lp(a) at entry and during the course
      of treatments directed at reducing plasma triglyceride levels. In each case, we
      found that at entry, Lp(a) peak density was correlated with LDL peak density
      (r=0.71, P<0.0001) and that during treatment, changes in plasma triglycerides
      were associated with shifts of Lp(a) peak density that paralleled those of LDL
      peak density. A high correlation (r=0.94, P<0.0001) was particularly evident in
      subjects with initial plasma triglycerides in the 300-mg/dL range. In vitro
      assembly studies showed that an apo(a) isoform containing 14 kringle IV type 2
      repeats, exhibited, on incubation with LDL, a comparable degree of incorporation
      into LDL species varying in density between 1.035 and 1.057 g/mL Taken together,
      our results indicate that metabolically dependent changes in the peak density of
      Lp(a) can occur independently of apo(a) size. These changes may have to be taken
      into account in assessing the cardiovascular pathogenicity of this lipoprotein
      particle in hypertriglyceridemic subjects.

PMID- 11451759
TI  - Discrimination of human coronary artery atherosclerotic lipid-rich lesions by
      time-resolved laser-induced fluorescence spectroscopy.
AB  - Lesion composition plays a significant role in atherosclerotic lesion instability
      and rupture. Current clinical techniques cannot fully characterize lesion
      composition or accurately identify unstable lesions. This study investigates the
      use of time-resolved fluorescence spectroscopy for unstable atherosclerotic
      lesion diagnosis. The fluorescence of human coronary artery samples was induced
      with nitrogen laser and detected in the 360- to 510-nm wavelength range. The
      samples were sorted into 7 groups according to the AHA classification: normal
      wall and types I, II(a) (fatty streaks), III (preatheroma), IV (atheroma), V(a)
      (fibrous), and V(b) (calcified) lesions. Spectral intensities and time-dependent
      parameters [average lifetime tau(f); decay constants: tau(1) (fast-term), tau(2)
      (slow-term), A(1) (fast-term amplitude contribution)] derived from the time
      resolved spectra of coronary samples were used for tissue characterization. We
      determined that a few intensity values at longer wavelengths (>430 nm) and time
      dependent parameters at peak emission region (390 nm) discriminate between all
      types of arterial samples except between normal wall and type I lesions. The
      lipid-rich lesions (more unstable) can be discriminated from fibrous lesions
      (more stable) on the basis of time-dependent parameters (lifetime and fast-term
      decay). We inferred that features of lipid fluorescence are reflected on lipid
      rich lesion emission. Our results demonstrate that analysis of the time-resolved
      spectra may be used to enhance the discrimination between different grades of
      atherosclerotic lesions and provide a means of discrimination between lipid-rich
      and fibrous lesions.

PMID- 11451760
TI  - Thromboregulation by endothelial cells: significance for occlusive vascular
      diseases.

PMID- 11451763
TI  - AHA Scientific Statement: Guide to anticoagulant therapy: heparin: a statement
      for healthcare professionals from the American Heart Association.

PMID- 11451764
TI  - A better oral rehydration solution?. An important step, but not a leap forward.

PMID- 11451765
TI  - Umbilical cord blood banks in the UK.

PMID- 11451766
TI  - Bridging the quality chasm.

PMID- 11451767
TI  - Prevention of type 2 diabetes.

PMID- 11451768
TI  - Wanted: a social contract for the practice of medicine.

PMID- 11451770
TI  - Eli Lilly violates patients' privacy.

PMID- 11451771
TI  - UK considers new compensation plan for NHS.

PMID- 11451772
TI  - US surgeons implant new artificial heart.

PMID- 11451774
TI  - Specialists question effectiveness of sex selection technique.

PMID- 11451775
TI  - Doctors may be able to detect Down's syndrome during IVF.

PMID- 11451776
TI  - BMA remains concerned about GMC structure.

PMID- 11451777
TI  - Revalidation proposals will waste time.

PMID- 11451778
TI  - BMA president warns doctors not to take public esteem for granted.

PMID- 11451779
TI  - BMA supports GPs' quest for new contract.

PMID- 11451780
TI  - Testing for Helicobacter pylori in dyspeptic patients suspected of peptic ulcer
      disease in primary care: cross sectional study.
AB  - OBJECTIVES: To develop an easily applicable diagnostic scoring method to
      determine the presence of peptic ulcers in dyspeptic patients in a primary care
      setting; to evaluate whether Helicobacter pylori testing adds value to history
      taking. DESIGN: Cross sectional study. SETTING: General practitioners' offices in
      the Utrecht area of the Netherlands. PARTICIPANTS: 565 patients consulting a
      general practitioner about dyspeptic symptoms of at least two weeks' duration.
      MAIN OUTCOME MEASURES: The presence or absence of peptic ulcer; independent
      predictors of the presence of peptic ulcer as obtained from history taking and
      the added value of H pylori testing were quantified by using multivariate
      logistic regression analyses. RESULTS: A history of peptic ulcer, pain on an
      empty stomach, and smoking were strong and independent diagnostic determinants of
      peptic ulcer disease, with odds ratios of 5.5 (95% confidence interval 2.6 to
      11.8), 2.8 (1.0 to 4.0), and 2.0 (1.4 to 6.0) respectively. The area under the
      receiver operating characteristic curve (ROC area) of these determinants together
      was 0.71. Adding the H pylori test increased the ROC area only to 0.75. However,
      in a group of patients at high risk, identified by means of a simple scoring rule
      based on history taking, the predictive value for the presence of peptic ulcer
      increased from 16% to 26% after a positive H pylori test. CONCLUSIONS: In the
      total group of dyspeptic patients in primary care, H pylori testing has no value
      in addition to history taking for diagnosing peptic ulcer disease. In a subgroup
      of patients at high risk of having peptic ulcer disease, however, it might be
      useful to test for and treat H pylori infections.

PMID- 11451781
TI  - A score for predicting risk of death from cardiovascular disease in adults with
      raised blood pressure, based on individual patient data from randomised
      controlled trials.
AB  - OBJECTIVE: To create a risk score for death from cardiovascular disease that can
      be easily used. DESIGN: Data from eight randomised controlled trials of
      antihypertensive treatment. SETTING: Europe and North America. PARTICIPANTS: 47
      088 men and women from trials that had differing age ranges and differing
      eligibility criteria for blood pressure. MAIN OTUCOME MEASURE: 1639 deaths from
      cardiovascular causes during a mean 5.2 years of follow up. RESULTS: Baseline
      factors were related to risk of death from cardiovascular disease using a
      multivariate Cox model, adjusting for trial and treatment group (active versus
      control). A risk score was developed from 11 factors: age, sex, systolic blood
      pressure, serum total cholesterol concentration, height, serum creatinine
      concentration, cigarette smoking, diabetes, left ventricular hypertrophy, history
      of stroke, and history of myocardial infarction. The risk score is an integer,
      with points added for each factor according to its association with risk. Smoking
      contributed more in women and in younger age groups. In women total cholesterol
      concentration mattered less than in men, whereas diabetes had more of an effect.
      Antihypertensive treatment reduced the score. The five year risk of death from
      cardiovascular disease for scores of 10, 20, 30, 40, 50, and 60 was 0.1%, 0.3%,
      0.8%, 2.3%, 6.1%, and 15.6%, respectively. Age and sex distributions of the score
      from the two UK trials enabled individual risk assessment to be age and sex
      specific. Risk prediction models are also presented for fatal coronary heart
      disease, fatal stroke, and all cause mortality. CONCLUSION: The risk score is an
      objective aid to assessing an individual's risk of cardiovascular disease,
      including stroke and coronary heart disease. It is useful for physicians when
      determining an individual's need for antihypertensive treatment and other
      management strategies for cardiovascular risk.

PMID- 11451782
TI  - Reduced osmolarity oral rehydration solution for treating dehydration due to
      diarrhoea in children: systematic review.
AB  - OBJECTIVES: To compare reduced osmolarity oral rehydration solution with standard
      World Health Organization oral rehydration solution in children with acute
      diarrhoea. DESIGN: Systematic review of randomised controlled trials. STUDIES: 15
      randomised controlled trials including 2397 randomised patients. OUTCOMES: The
      primary outcome was unscheduled intravenous infusion; secondary outcomes were
      stool output, vomiting, and hyponatraemia. RESULTS: In a meta-analysis of nine
      trials for the primary outcome, reduced osmolarity rehydration solution was
      associated with fewer unscheduled intravenous infusions compared with standard
      WHO rehydration solution (odds ratio 0.61, 95% confidence interval 0.47 to 0.81).
      Three trials reported that no patients required unscheduled intravenous infusion.
      Trials reporting secondary outcomes suggested that in the reduced osmolarity
      rehydration solution group, stool output was lower (standardised mean difference
      in the log scale -0.214 (95% confidence interval -0.305 to -0.123; 13 trials) and
      vomiting was less frequent (odds ratio 0.71, 0.55 to 0.92; six trials). Six
      trials sought presence of hyponatraemia, with events in three studies, but no
      significant difference between the two arms. CONCLUSION: In children admitted to
      hospital with dehydration associated with diarrhoea, reduced osmolarity
      rehydration solution is associated with reduced need for unscheduled intravenous
      infusions, lower stool volume, and less vomiting compared with standard WHO
      rehydration solution.

PMID- 11451783
TI  - Drug points: Neonatal convulsions after withdrawal of baclofen.

PMID- 11451784
TI  - Randomised controlled trial of disclosure of emotionally important events in
      somatisation in primary care.
AB  - OBJECTIVE: To test whether a disclosure intervention improves subjective health
      and reduces medical consumption and sick leave in somatising patients in general
      practice. DESIGN: Non-blind randomised controlled trial. SETTING: 10 general
      practices in the Netherlands. PARTICIPANTS: 161 patients who frequently attended
      general practice with somatising symptoms. INTERVENTION: Patients in the
      intervention group were visited two to three times and invited to disclose
      emotionally important events in their life. Control patients received normal care
      from their general practitioners. MAIN OUTCOME MEASURES: Use of medical services
      (drugs and healthcare visits), subjective health, and sick leave assessed by self
      completion questionnaires after 6, 12, and 24 months. RESULTS: Of the 161
      patients, 137 completed the trial (85%). Both groups were comparable at baseline.
      The intervention had no effect on the main outcome measures at any point.
      Intervention patients made one more visit to health care (95% confidence interval
      -4 to 6); the use of medicines did not change in both groups (-1 to 1);
      subjective health improved 3.6 points more in the control group (-11.2 to 4.3);
      and disclosure patients were on sick leave one more week (-1 to 3). Patients
      often had a depression or anxiety disorder for which they were not receiving
      adequate care. CONCLUSION: Although the intervention was well received by
      patients and doctors, disclosure had no effect on the health of somatising
      patients in general practice.

PMID- 11451785
TI  - Can primary care groups and trusts improve health?

PMID- 11451786
TI  - Regular review: Endometriosis.

PMID- 11451787
TI  - Unsuspected nephrogenic diabetes insipidus.

PMID- 11451788
TI  - Oxygen treatment for acute severe asthma.

PMID- 11451790
TI  - Systematic reviews in health care: Investigating and dealing with publication and
      other biases in meta-analysis.

PMID- 11451802
TI  - Less is more?

PMID- 11451803
TI  - Cryotherapy in early lung cancer.

PMID- 11451804
TI  - Re-emergence of an "orphan" test for pulmonary embolism.

PMID- 11451805
TI  - Should echocardiography of the right ventricle help determine who receives
      thrombolysis for pulmonary embolism?

PMID- 11451806
TI  - Idiopathic pulmonary fibrosis challenges for the future.

PMID- 11451807
TI  - Nosocomial urinary tract infections and the indwelling catheter: what is new and
      what is true?

PMID- 11451809
TI  - Heimlich valve in the management of pneumothorax in patients with advanced AIDS.
AB  - STUDY OBJECTIVES: To review therapeutic strategies in the management of
      pneumothorax in patients with AIDS. DESIGN: Retrospective, 7-year, single
      institution experience. PATIENTS: Forty-seven patients with AIDS were treated for
      59 pneumothoraxes. Mean age was 37.4 years, and 70% of patients had prior or
      current infection with Pneumocystis carinii. All patients had CD4+ counts of <
      100, and 28 of 47 patients (59.6%) had CD4+ counts of < 50. Of 59 pneumothoraxes,
      14 pneumothoraxes (23.7%) were iatrogenic and 16 pneumothoraxes (27.1%) were
      bilateral. Patients were treated with conventional strategy (tube thoracostomy
      [TT] with or without pleurodesis, thoracotomy with blebectomy) or converted to a
      Heimlich valve (HV) in case of failure of conventional management. RESULTS:
      Thirty-six of 47 patients (76.6%) were discharged, and only 26 of 36 patients
      (72.2%) had complete pneumothorax resolution at discharge after conventional
      treatment. All patients discharged with an HV (10 of 36 patients; 27.8%) had
      pneumothorax resolution followed by valve removal as outpatients. Mean hospital
      stay after chest decompression was 12 days for conventional-therapy group
      survivors and 3 days for patients treated with an HV. Thirteen patients died
      (27.7%) with follow-up to 60 days. In-hospital mortality was 23.4% (11 of 47
      patients), which represented a 29.7% mortality for patients treated with
      conventional therapy. Patients treated with an HV had no in-hospital mortality
      and 100% pneumothorax resolution, with two deaths occurring within 60 days of
      discharge but after removal of the HV. CONCLUSIONS: Patients with advanced AIDS
      and pneumothorax have high associated morbidity and mortality. If no resolution
      is observed after simple TT, prompt conversion to an HV allows safe and early
      hospital discharge.

PMID- 11451810
TI  - Use of small-bore vs large-bore chest tubes for treatment of malignant pleural
      effusions.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of small-bore (12 French vanSonnenberg)
      catheters compared with standard large-bore chest tubes in the drainage and
      sclerotherapy of malignant pleural effusions. DESIGN: Retrospective review.
      SETTING: An academic tertiary care hospital. PATIENTS: Adult patients with
      documented neoplasms and malignant pleural effusions, treated between 1986 and
      1995. INTERVENTION: All patients included in the study underwent drainage of
      malignant pleural effusions either by large-bore chest tube or by ultrasound
      guided small-bore catheter. After drainage, pleurodesis was performed. RESULTS:
      Outcome as defined by recurrence of effusion was determined by blinded
      examination of all postpleurodesis chest radiographs. We identified 58 cases of
      malignant pleural effusion in which small-bore catheters were used and 44 in
      which large-bore chest tubes were used. The majority of patients had breast (n =
      56, 55%) or lung cancer (n = 29, 28%). The median age was 65 years. Fifty-nine
      patients were actively being treated with chemotherapy at the time of
      pleurodesis. The following sclerosing agents were used: talc, 27 (26%);
      tetracycline, 72 (70%); bleomycin, 2 (2%); and interferon, 1 (1%). Actuarial
      probabilities of recurrence at 6 weeks and 4 months were 45% and 53% for the
      small tubes vs 45% and 51% for the large tubes. Univariate and multivariate
      analyses failed to demonstrate that tube size had any influence on the rate of
      recurrence. CONCLUSIONS: We were unable to detect any major differences in
      outcomes with the use of either size of chest tube. Our study suggests that small
      bore catheters may be effective in the treatment of malignant pleural effusions
      and deserve further evaluation in prospectively designed trials.

PMID- 11451811
TI  - Cryotherapy in early superficial bronchogenic carcinoma.
AB  - BACKGROUND: Treatment of early superficial bronchogenic carcinoma (ESBC) is under
      debate, and no consensus has been achieved. Different therapeutic methods have
      been proposed, including surgical resection and endoscopic methods. STUDY
      OBJECTIVE: To assess the efficacy of cryotherapy in patients with ESBC. PATIENTS
      AND METHODS: Patients included in the study had histologically proven ESBC after
      fiberoptic bronchoscopy. Cryotherapy was performed through a rigid bronchoscope.
      Efficacy was assessed by endoscopy with multiple biopsies 1 month after treatment
      and during the follow-up period. Parameters studied were response to treatment,
      adverse effects, and survival. RESULTS: We included 35 patients (34 men and 1
      woman). The mean age was 61 +/- 9 years. Multiple locations of ESBC were observed
      in seven patients (20%). Complete response rate at both 1 month and 1 year was
      91% (32 patients). No severe adverse effects were noted. Local recurrence was
      observed within 4 years in 10 patients (28%). A follow-up period of at least 4
      years was available in 22 patients; of them, 11 patients (50%) were long-term
      survivors. CONCLUSION: Our results suggest that cryotherapy is an effective
      method of treatment in patients with ESBC. Due to its relative tolerance compared
      to surgery, cryotherapy could be proposed as a first-line therapy in this
      population with high carcinogenic risk.

PMID- 11451812
TI  - Lung cancer treated surgically in patients <50 years of age.
AB  - STUDY OBJECTIVES: Some investigators have suggested that lung cancer in young
      patients has a more aggressive course and a poorer prognosis than lung cancer in
      older patients. The aim of this study was to determine if the basal
      characteristics and survival in younger patients with lung cancer undergoing
      surgical resection differ from those of older patients. DESIGN: Retrospective
      clinical study. PATIENTS: Of 1,208 consecutive patients who underwent surgery for
      primary lung cancer between June 1984 and March 2000, we reviewed the medical
      records of 110 younger patients who were < 50 years of age at the time of surgery
      and compared them with 1,098 older patients (> or = 50 years of age). All deaths
      were included. RESULTS: In the younger patient group, asymptomatic disease and
      adenocarcinoma was significantly more frequent, the rate of smoking was
      significantly higher, and the amount of smoking (Brinkman index) was
      significantly larger. For the 94 younger patients with complete resection, the 5
      year survival rate was 61.0%, which was not significantly higher than that for
      the 923 older patients (57.7%). However, the 53 younger patients with stage I
      disease (5-year survival of 84.3%) had significantly better survival than older
      patients with the same condition (71.6%). Survival of patients in stage II or
      stage III disease was not significantly different. CONCLUSION: The younger
      patients had significantly better prognoses, and a statistical difference was
      shown especially in the early stage, while in the advanced stage the malignancy
      of the lung cancer itself surpassed the difference in survival.

PMID- 11451813
TI  - Lung cancer resection: the prediction of postsurgical outcomes should include
      long-term functional results.
AB  - STUDY OBJECTIVES: To assess (1) the possibility of predicting long-term
      postoperative lung function, and (2) the usefulness of maximal oxygen consumption
      (O(2)max) as a criterion for operability and as a predictor of long-term
      disability. DESIGN: Prospective study. SETTING: Outpatients and inpatients of a
      university hospital. PARTICIPANTS: Sixty-two consecutive patients (mean +/- SD
      age, 62 +/- 8 years; 51 male and 11 female patients) were preoperatively
      evaluated for lung cancer resection (pneumonectomy or bilobectomy [n = 14] and
      lobectomy [n = 48]). MEASUREMENTS: Clinical examination and recorded respiratory
      symptoms and spirometry results before surgery and 6 months after surgery. If
      predicted postoperative FEV(1) (ppoFEV(1)) was < 40%, patients underwent exercise
      testing; if O(2)max was between 10 mL/kg/min and 20 mL/kg/min, patients underwent
      a split-function study. RESULTS: All the patients with ppoFEV(1) > or = 40%-even
      those patients (26%) with FEV(1) < 80%-underwent thoracotomy without further
      tests. Seven patients with ppoFEV(1) < 40% underwent exercise testing, and three
      of them underwent a split-function study. Nine patients (15%; including six
      patients with COPD and one patient with asthma) had immediate postoperative
      complications (pneumonia [n = 5] and respiratory failure [n = 4]); seven of these
      patients had ppoFEV(1) > or = 40%. ppoFEV(1) significantly underestimated the
      actual postoperative FEV(1) (poFEV(1); p < 0.001) 6 months after pneumonectomy or
      bilobectomy but was reliable for actual poFEV(1) after lobectomy. Two patients
      with predicted postoperative O(2)max > 10 mL/kg/min became oxygen dependent and
      had marked limitation of daily living. CONCLUSIONS: ppoFEV(1) > or = 40% reliably
      identifies patients not requiring further tests and not at long-term risk of
      respiratory disability. O(2)max, effective for defining the immediate surgical
      risk, is not useful in predicting long-term disability.

PMID- 11451814
TI  - Fiberoptic bronchoscopic balloon dilatation in malignant tracheobronchial
      disease: indications and results.
AB  - STUDY OBJECTIVES: Bronchoscopic balloon dilatation (BBD) has become a valuable
      tool in the treatment of benign tracheobronchial stenoses. The objective of this
      study was to assess indications for and results of fiberoptic BBD in treating
      malignant lesions. DESIGN: One hundred twenty-six balloon dilatation procedures
      were performed in 78 patients with predominantly bronchial carcinoma. BBD was
      only performed when alternative modes of local treatment (eg, laser therapy or
      stent implantation) were not indicated or were inappropriate. Indications were
      symptomatic stenoses of the tracheobronchial tree: dyspnea or stridor (52%),
      retention pneumonia (15%), atelectasis (10%), retention of secretions (21%), or
      lung abscess (2%). RESULTS: Fifty-five percent of all procedures consisted of
      dilatations of tracheal or bronchial lesions (group 1). In 22% of procedures, a
      stent was dilated (group 2). In 13%, BBD was used to facilitate stent placement
      (group 3), and in 10% to enable the correct positioning of irradiation probes for
      brachytherapy (group 4). In group 1 and group 2, 2 of 2 lung abscesses resolved,
      5 of 8 atelectases resolved, and 11 of 12 retention pneumonias resolved. Dyspnea
      improved in only 12 of 32 patients. No abscess recurred. Two pneumonias and two
      atelectases reappeared due to restenosis. Stent implantation and brachytherapy
      procedures were facilitated in 90% of cases. In 52% of cases, BBD was supported
      by high-frequency jet ventilation. Complications consisted of one fatal
      hemoptysis caused by a lacerated pulmonary artery, and minor bleeding not
      necessitating specific therapy. CONCLUSIONS: Fiberoptic BBD is useful in the
      management of airway stents prior to and postimplantation, as well as in the
      placement of brachytherapy catheters. BBD is also successful in the resolution of
      poststenotic lung abscesses, retention pneumonias, and atelectases.

PMID- 11451815
TI  - Primary intrathoracic malignant effusion: a descriptive study.
AB  - BACKGROUND: Patients who present with malignant pleural/malignant effusion
      without a definite primary site are not well described in the medical literature.
      In the course of our clinical practice, we have observed certain traits that are
      peculiar to patients with such a presentation. We have applied the term primary
      intrathoracic malignant effusion (PIME) to describe this condition. STUDY
      OBJECTIVES: Patients must fulfill the following criteria before a diagnosis of
      PIME can be made: clinical presentation dominated by pleural/pericardial
      effusion; histologic proof of malignancy obtained from the pleura and/or
      pericardium; no definite primary site in the lungs or elsewhere from CT scan of
      the chest, chest radiograph, or physical and endoscopic examination; no history
      of malignancy; and no history of asbestos exposure. Exposure to environmental
      tobacco smoke (ETS) among the nonsmokers was examined in a case-control setting.
      METHODS: We conducted a retrospective search of our database of patients who were
      referred to the Department of Medical Oncology with a diagnosis of
      pleural/pericardial effusion from January 1993 to January 2000. RESULTS: Seventy
      one of 200 patients from our database met the criteria. A significant majority of
      the patients were women (65%) and nonsmokers (72%). All patients had
      adenocarcinoma shown on biopsy. The majority of patients (63%) had disease
      localized to the intrathoracic serosal surfaces; the rest had distant metastases
      involving the lung (50%), bone (27%), liver (19%), brain (8%), and skin (4%). Six
      patients had two or more sites of distant metastases. There was a significant
      association with ETS exposure when compared to a control group comprised of
      patients with colonic cancer, matched for sex and age. The median survival was 10
      months for patients with disease localized to the pleura/pericardium and 7 months
      for those with distant metastases. Thirty-eight patients (54%) received
      chemotherapy. All had platinum-based chemotherapy, except for three patients. The
      median survival for patients treated or not treated with chemotherapy was 12
      months and 5 months, respectively. This difference in survival was statistically
      significant (p = 0.003). CONCLUSIONS: PIME should be viewed as a distinct entity.
      Its etiology remains largely unknown, although exposure to environmental tobacco
      smoke may play a part. Platinum-based chemotherapy may have a positive biological
      effect on this disease. More studies are required to elucidate the epidemiology,
      possible etiologic factors, and treatment options for this group of patients.

PMID- 11451816
TI  - Impact of race in lung cancer: analysis of temporal trends from a surveillance,
      epidemiology, and end results database.
AB  - STUDY OBJECTIVES: We analyzed data from a community-based cancer database over a
      26-year period in order to characterize clinicopathologic differences between
      black and white patients with lung cancer, and to identify relevant temporal
      trends in incidence and survival. DESIGN, SETTING, AND PATIENTS: Data on
      demographics, stage, histology, and survival were obtained on all black and white
      patients with primary bronchogenic carcinoma registered in the community-based
      metropolitan Detroit Surveillance, Epidemiology, and End Results database from
      1973 to 1998. RESULTS: Of 48,318 eligible patients, 23% were black. Lung cancer
      incidence rates decreased for men of both races from 1985 to 1998, with a greater
      decline occurring in black men (p < 0.0001). Although incidence rates declined
      over time for men of both races < 50 years of age, this decrease was greater in
      white men, resulting in an increase in the racial differential in younger men.
      Temporal trends in incidence rates were similar for women of both races. The
      incidence of distant-stage disease was higher among blacks throughout the study
      period. The incidence of local-stage disease decreased for both races, though
      this decline was greater in blacks. A significant racial difference in 2-year and
      5-year survival rates developed during the study period, due to a distinct lack
      of improvement in black patients. In a multivariate model, the relative risks of
      death for black patients, relative to white patients, were 1.24 (p < 0.0001) for
      local stage, 1.14 (p < 0.0001) for regional stage, and 1.03 (p = 0.045) for
      distant stage. CONCLUSION: Significant racial differences exist in the incidence
      and survival rates for lung cancer in metropolitan Detroit. Since 1973, several
      disturbing trends have developed, particularly with regard to the lack of
      improvement in overall survival in black patients. Further study is required to
      determine the factors responsible for these temporal trends.

PMID- 11451817
TI  - Reliability and validity of chest radiograph surveillance programs.
AB  - STUDY OBJECTIVES: Due to the lack of consensus in the literature in the use of
      posteroanterior (PA) vs PA with right and left oblique views as the optimum
      radiograph surveillance methodology to investigate pleural changes, a study was
      undertaken to evaluate the reliability, sensitivity, and specificity of these two
      approaches. DESIGN: Three experienced radiologist B readers used the 1980
      International Labor Office classification system for pneumoconiosis to
      independently read chest radiographs of workers with individual identifiers
      masked. All radiographs were read first as a PA view only. Unknown to the B
      readers, each subject's PA was then matched to his or her corresponding right and
      left oblique views (film triad) and re-read several weeks later. SETTING AND
      PARTICIPANTS: The respiratory health of 652 workers exposed to refractory ceramic
      fiber was assessed as part of cross-sectional and longitudinal surveillance
      programs. MEASUREMENTS AND RESULTS: kappa Statistics for interreader and
      intrareader reliability between the PA view and film triad methods were
      calculated. Sensitivity, specificity, and positive predictive value were assessed
      by comparing the initial cross-sectional study to the longitudinal study. The
      film triad method had considerably higher interreader reliability (kappa = 0.59)
      compared to the PA-only method (kappa = 0.44). Results from the initial cross
      sectional study were then compared to findings evaluated longitudinally. The film
      triad again was superior, demonstrating a positive predictive value of 73.7%
      compared to only 47.8% for the PA method. CONCLUSIONS: It is our recommendation
      that the film triad method be used in surveillance studies where both parenchymal
      and pleural changes are anticipated.

PMID- 11451818
TI  - Forced oscillation technique to evaluate tracheostenosis in patients with
      neurologic injury.
AB  - STUDY OBJECTIVES: To determine the utility of forced oscillation technique (FOT)
      for measuring pulmonary resistance and reactance in patients with central nervous
      system injuries, for detection and follow-up of posttracheostomy tracheal
      stenosis. DESIGN: Case series. SETTING: A rehabilitation hospital, Brasilia,
      Distrito Federal, Brazil. PATIENTS: Ten consecutive neurologically impaired
      patients, who had previously undergone tracheostomies, with tracheostenosis
      without current tracheostomy or other tracheal lesion. INTERVENTIONS AND
      MEASUREMENTS: FOT evaluations were compared to tracheal diameter before and after
      bronchoscopic tracheostenosis dilatation procedures. Forced spirometry
      examinations were also obtained and compared. RESULTS: Tracheal stenotic lesions
      were characterized by marked increase in resistance and reduction in reactance at
      low frequency and a marked increase in resonance frequency (Rf). Consistent
      reversal of this pattern with large reductions in total impedance of the
      respiratory system (Zresp) Rf and resistance at 5 Hz (R 5 Hz) were noted in all
      patients after each successful dilatation. Diameter of the stenosis was strongly
      correlated with Rf, Zresp, and R 5 Hz. The change in diameter before and after
      dilatation was similarly correlated with the changes in FOT values of Rf and
      Zresp. Spirometry values did not correlate well with the diameter of the tracheal
      stenosis. CONCLUSION: The strong correlation of Rf, Zresp, and R 5 Hz to diameter
      of tracheostenosis suggests a previously unappreciated role for FOT in the
      noninvasive detection and follow-up of airway stenosis. This may be especially
      useful for patients with concomitant neurologic disabilities who are at risk of
      airway stenosis.

PMID- 11451819
TI  - An 8-year follow-up of carbon monoxide diffusing capacity in a general population
      sample of northern italy.
AB  - STUDY OBJECTIVE: Diffusing capacity of the lung for carbon monoxide (DLCO) is
      frequently assessed as part of a thorough pulmonary function assessment in
      patients with pulmonary or cardiopulmonary diseases. However, little information
      regarding the longitudinal trends of DLCO is available. In this study, we
      examined the temporal trends in DLCO to determine the effects of smoking and
      changes in smoking habits. DESIGN: A longitudinal study was recently conducted in
      the Po River Delta area of northern Italy, in which DLCO measurements were taken
      approximately 8 years apart in the same subjects; this offered the unique
      opportunity to assess the temporal changes in DLCO. The longitudinal DLCO data
      were analyzed independently in two age groups (20 to 40 years, and > or = 40
      years) using a repeated-measures analysis. RESULTS: Included were 928 subjects >
      20 years old who had DLCO assessments both at baseline and follow-up. Male
      subjects had higher mean levels of DLCO than female subjects in the older age
      group (> or = 40 years). Continuous smokers had significantly lower DLCO levels
      than "never-smokers," but their changes in DLCO during follow-up were the same.
      This suggests that the lung damage due to smoking had occurred prior to DLCO
      testing. We also found that the annual decline in DLCO accelerated with age in
      adults > or = 40 years old. CONCLUSIONS: We conclude that in adults > or = 40
      years of age from the general population, DLCO accelerates downwards regardless
      of gender, smoking, and initial FEV(1) level.

PMID- 11451820
TI  - Cardiopulmonary exercise testing in children: an individualized protocol for
      workload increase.
AB  - OBJECTIVES: To investigate the feasibility of individualized workload increments,
      as used in adults, for exercise testing in children; and to investigate whether
      this individualized protocol makes it possible to satisfy the usual criteria for
      maximal exercise (clinical exhaustion, predicted maximum heart rate [HRmax],
      oxygen uptake [O(2)] plateau, maximal respiratory exchange ratio > 1.1). DESIGN:
      Prospective clinical study. SETTING: Pediatric exercise testing laboratory.
      SUBJECTS: Ninety-two children aged 5 to 17 years with various cardiac and
      respiratory diseases (33 with asthma, 11 with bronchopulmonary dysplasia, 6 with
      cystic fibrosis, 10 with congenital heart disease, and 32 miscellaneous).
      INTERVENTIONS: Individualized maximal incremental exercise testing. The increase
      in workload was adapted to the individual and was calculated from predicted
      maximal oxygen uptake (O(2)max) for each child. The test lasted 10 to 12 min.
      RESULTS: The exercise test was well tolerated by all children and was maximal in
      all but seven patients. A total of 65.7% of children reached the predicted
      O(2)max and 68.4% satisfied the criteria for a O(2) plateau at peak exercise. The
      predicted HRmax was achieved in all but two children. The mean maximal
      respiratory exchange ratio was 1.06. CONCLUSION: The individualized protocol for
      increasing workload, based on O(2) rather than power, was well tolerated by
      children. In our view, the best two criteria for assessing the maximality of the
      tests were clinical exhaustion and HRmax, especially if the O(2) plateau was not
      reached. These results suggest that individualized protocols could be used
      instead of standardized tests for exercise testing in children.

PMID- 11451821
TI  - Predictors of oxygen desaturation during submaximal exercise in 8,000 patients.
AB  - STUDY OBJECTIVES: To determine predictors of oxygen desaturation during
      submaximal exercise in patients with various lung diseases. DESIGN AND SETTING:
      This retrospective case series used pulmonary function laboratory results from
      all patients referred to a major tertiary-care center. PATIENTS AND MEASUREMENTS:
      All patients > or = 35 years old who underwent spirometry, diffusing capacity of
      the lung for carbon monoxide (DLCO), lung volumes, and pulse oximetry during 3
      min submaximal step-test exercise during 1996 were included (4,545 men and 3,472
      women). Logistic regression models, correcting for gender, age, and weight,
      determined the odds ratios (ORs) for oxygen desaturation of > or = 4% during
      exercise for each category of lung function abnormality (compared to those with
      entirely normal lung function). RESULTS: Approximately 74% of the patients had
      airways obstruction, while only 5.6% had restriction of lung volumes. One third
      of those with obstruction had a low DLCO, compared to 56% with restriction, while
      2.7% had a low DLCO without obstruction or restriction. The risk of oxygen
      desaturation during submaximal exercise was very high (OR, 34) in patients with
      restriction and low DLCO (as in interstitial lung disease) and in patients with
      obstruction and low DLCO (as in COPD; OR, 18), intermediate (OR, 9) in patients
      with only a low DLCO, and lowest in those with a normal DLCO (OR, 4 if
      restricted; OR, 2 if obstructed). A cut point of DLCO < 62% predicted resulted in
      75% sensitivity and specificity for exercise desaturation. No untoward cardiac
      events occurred in any patients during or following the submaximal exercise
      tests. CONCLUSIONS: The risk of oxygen desaturation during submaximal exercise is
      very high in patients with a low DLCO. Submaximal exercise tests are safe, even
      in elderly patients with heart and lung diseases.

PMID- 11451822
TI  - Sarcoidosis: the value of exercise testing.
AB  - STUDY OBJECTIVES: To evaluate exercise testing for the assessment of the extent
      of pulmonary disease in patients with sarcoidosis. DESIGN: Retrospective analysis
      of consecutive patients with sarcoidosis referred to the Pulmonary Physiology
      Laboratory between 1992 and 1997, who completed at least 6 min of progressive
      bicycle exercise. Resting and exercise pulmonary function measurements were
      compared to radiographic stage of disease. SETTING: Pulmonary Physiology
      Laboratory at Washington, DC, Veterans Affairs Medical Center. PATIENTS: Forty
      eight outpatient veterans with biopsy specimen-proven sarcoidosis. RESULTS:
      Across all radiographic stages of sarcoidosis, total lung capacity, resting
      diffusing capacity, and exercise gas exchange measurements had a significant
      variance with radiographic stage. Across the early radiographic stage disease
      (stages 0 to 2), the change in alveolar-arterial oxygen pressure gradient between
      rest and exercise, normalized for oxygen uptake, was the most significant
      measurement in its variation with radiographic stage. CONCLUSIONS: Changes in gas
      exchange with exercise may be the most sensitive physiologic measurements to
      assess the extent of disease in early radiographic stages of sarcoidosis.

PMID- 11451823
TI  - Respiratory muscle strength, lung function, and dyspnea in patients with
      sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous disorder that is estimated to
      involve the skeletal muscles in up to 50% of patients. There is little
      information on the relationship among respiratory muscle strength, lung volumes,
      and the degree of dyspnea in patients with sarcoidosis. DESIGN AND PATIENTS: Lung
      function and maximal respiratory muscle force generation were measured in 36
      patients with sarcoidosis (24 patients with pulmonary parenchymal infiltration)
      and 25 control subjects free of cardiorespiratory disease. Dyspnea in the
      sarcoidosis patients was quantitated by a score based on an activity tolerance
      assessment scale (ranging from rest to climbing hills or stairs). SETTING:
      Outpatient clinics of two teaching hospitals. RESULTS: Mean FVC, maximal
      voluntary ventilation, total lung capacity (TLC), functional residual capacity,
      residual volume (RV), and diffusing capacity of the lung for carbon monoxide
      (DLCO) were all at least 16% less than corresponding control values (in all
      cases, p < 0.001), while maximal inspiratory mouth pressure (PImax) and maximal
      expiratory mouth pressure (PEmax) were 37% and 39% less, respectively, than
      control values (both at p < 0.0001). PImax and PEmax declined with increasing
      dyspnea in a more graded, steady manner than did spirometric and DLCO values. For
      all measurements, however, the lowest mean values were found in patients with the
      most severe level of dyspnea. Strong inverse relationships were observed between
      PEmax and PImax with dyspnea level (p < 0.0001 and p < 0.01, respectively). Both
      PImax and PEmax correlated best with absolute values of FVC, while only PEmax
      correlated with RV (absolute and percent predicted) and percent predicted values
      of TLC. CONCLUSIONS: Maximal respiratory pressures correlate more closely with
      dyspnea level than lung volumes and DLCO. Since dyspnea is the most common
      presentation in early to moderately advanced sarcoidosis, respiratory pressures
      may be a more reliable index of functional work capacity and reflection of
      activities of daily living than standard tests of lung function.

PMID- 11451824
TI  - Endobronchial biopsy for sarcoidosis: a prospective study.
AB  - STUDY OBJECTIVES: To determine the yield of endobronchial biopsy (EBB) for
      suspected sarcoidosis, and to evaluate if EBB increases the diagnostic value of
      fiberoptic bronchoscopy (FOB) when added to transbronchial biopsy (TBB). DESIGN:
      Prospective study of consecutive patients. SETTING: Pulmonary clinic of a
      tertiary-care, academic medical center. PATIENTS: Patients consecutively referred
      for suspected pulmonary sarcoidosis. INTERVENTIONS: All patients having FOB
      performed underwent an evaluation that included history, physical examination, a
      chest radiograph, and spirometry. During FOB, airway appearance was recorded and
      both TBB and EBB were performed in a standardized fashion. Six TBB specimens were
      obtained, as were six EBB samples. For patients with abnormal-appearing airways,
      four specimens were obtained from the abnormal-appearing airways and two
      specimens were obtained from the main carina. In patients with normal-appearing
      airways, four specimens were obtained from a secondary carina and two specimens
      were obtained from the main carina. A biopsy finding was considered positive if
      it demonstrated nonnecrotizing granulomas with special stains that were negative
      for fungal and mycobacterial organisms. MEASUREMENTS AND RESULTS: The study
      cohort included 34 subjects (mean +/- SD age, 37.9 +/- 6.8 years; 58.8% were
      male; 64.7% were African American). EBB findings were positive in 61.8% of
      patients, while TBB showed nonnecrotizing granulomas in 58.8% of subjects. The
      addition of EBB increased the yield of FOB by 20.6%. Although EBB findings were
      more frequently positive in abnormal-appearing airways (p = 0.014), EBB provided
      diagnostic tissue in 30.0% of patients with normal-appearing endobronchial
      mucosa. There were no complications resulting from the addition of EBB to TBB.
      CONCLUSIONS: Endobronchial involvement is common in sarcoidosis. EBB has a yield
      comparable to TBB and can safely increase the diagnostic value of FOB.
      Pulmonologists should consider routinely performing EBB in cases of suspected
      sarcoidosis.

PMID- 11451825
TI  - Steady-state end-tidal alveolar dead space fraction and D-dimer: bedside tests to
      exclude pulmonary embolism.
AB  - STUDY OBJECTIVE: Less than 35% of patients suspected of having pulmonary embolism
      (PE) actually have PE. Safe bedside methods to exclude PE could save health-care
      resources and improve access to diagnostic testing for suspected PE. In patients
      with suspected PE, we sought to determine the sensitivity, specificity, and
      negative predictive value of (1) a steady-state end-tidal alveolar dead space
      fraction (AVDSf) of < 0.15, (2) a negative D-dimer result, and (3) the
      combination of a steady-state end-tidal AVDSf of < 0.15 and a negative D-dimer
      result. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary-care center in
      Ottawa, Ontario, Canada. PATIENTS: Consecutive inpatients, outpatients, and
      emergency department patients with suspected PE referred to the Departments of
      Nuclear Medicine or Radiology for investigation of suspected PE. INTERVENTIONS
      AND MEASUREMENTS: All study patients had D-Dimer and alveolar dead space
      measurements prior to determining outcome (PE or no PE) with
      ventilation/perfusion scans and/or noninvasive leg vein imaging and/or pulmonary
      angiography. RESULTS: Two hundred forty-six eligible and consenting patients
      underwent diagnostic imaging that excluded PE in 163 patients, diagnosed PE in 49
      patients, and was indeterminant in 34 patients. A negative D-dimer result
      excluded PE with a sensitivity of 83.0% (95% confidence interval [CI], 69.2 to
      92.4%), a negative predictive value of 91.2% (95% CI, 83.4 to 96.1%), and a
      specificity of 57.6%. A steady-state end-tidal AVDSf of < 0.15 excluded PE with a
      sensitivity of 79.5% (95% CI, 63.5 to 90.7%), a negative predictive value of
      90.7% (95% CI, 82.5 to 95.9%), and a specificity of 70.3%. The combination of a
      negative D-dimer result and a steady-state end-tidal AVDSf of < 0.15 excluded PE
      with a sensitivity of 97.8% (95% CI, 88.5 to 99.9%), a negative predictive value
      of 98.0% (95% CI, 89.4 to 99.9%), and a specificity of 38.0%. CONCLUSION: This
      simple combination of bedside tests may safely rule out PE without further
      diagnostic testing in large numbers of patients with suspected PE.

PMID- 11451826
TI  - Thrombolysis or heparin therapy in massive pulmonary embolism with right
      ventricular dilation: results from a 128-patient monocenter registry.
AB  - STUDY OBJECTIVES: To assess the potential benefit of thrombolysis in patients
      with massive pulmonary embolism (PE) with stable hemodynamics and right
      ventricular dysfunction. DESIGN: Retrospective, cohort study. SETTING: University
      based, tertiary referral medical center. PATIENTS: One hundred fifty-three
      consecutive patients with massive PE from January 1992 to December 1997 treated
      with heparin or thrombolysis. MEASUREMENTS AND RESULTS: Massive PE was confirmed
      by perfusion lung scan or pulmonary angiography. Right ventricular dysfunction
      was assessed by echocardiography (right ventricular/left ventricular [RV/LV]
      diastolic diameter ratio > 0.6) in all patients. In order to study a homogeneous
      population, 64 patients treated with thrombolysis (group 1) were matched on
      baseline RV/LV diameter ratio to 64 patients treated with heparin (group 2).
      Perfusion lung scan was repeated at day 7 to day 10. Mean relative improvement in
      perfusion lung scans was higher in group 1 than group 2 (54% vs 42%,
      respectively). PE recurrences were the same in both groups (4.7%; n = 3). There
      were no bleeding complications and no deaths in group 2. Conversely, in group 1,
      15.6% (n = 10) of patients suffered from bleeding (4.7%; n = 3 with intracranial
      bleeding) and 6.25% (n = 4) of them died. CONCLUSIONS: The results of this
      monocenter registry do not support the indication for thrombolysis in patients
      suffering from massive PE with stable hemodynamics and right ventricular
      dysfunction. Appropriate therapy in such patients still remains unknown. Further
      prospective randomized trials should be performed.

PMID- 11451827
TI  - Alveolar hemorrhage as a complication of treatment with abciximab.
AB  - STUDY OBJECTIVE: The use of abciximab, a chimeric monoclonal antibody Fab
      fragment specific for platelet glycoprotein IIb/IIIa receptors, is associated
      with improved outcome after angioplasty and stent placement. Major complications
      include bleeding, but pulmonary hemorrhage has been reported rarely. This study
      was done to identify patients with pulmonary hemorrhage following abciximab
      infusion and to define, if possible, any specific risk factors. DESIGN:
      Retrospective review of institutional coronary angiography and bronchoscopy
      databases to identify patients who received abciximab and developed pulmonary
      hemorrhage. SETTING: Tertiary-care teaching hospital. PATIENTS: All patients who
      underwent coronary angiography and received abciximab between June 1995 and March
      2000. INTERVENTION: None. MEASUREMENTS AND RESULTS: Seven of 2,553 patients
      (0.27%) had documented severe pulmonary hemorrhage associated with chest
      radiographic abnormalities, impaired oxygenation, and the need for blood product
      transfusions. The initial symptom was hemoptysis in four of the seven patients.
      There were two early deaths and one late death. No cases of pulmonary hemorrhage
      were identified in 5,412 patients who underwent coronary procedures without
      abciximab infusion. No other risk factors predicting hemorrhage were identified.
      CONCLUSIONS: Severe pulmonary hemorrhage is a complication of abciximab use.
      Although hemoptysis is an important alerting symptom, it may not be present
      initially and the diagnosis may be missed or considered late, with the potential
      for inappropriate treatment until the diagnosis is established. Lesser degrees of
      bleeding are potentially easily missed, and this report should alert physicians
      to this complication so that it can be considered early in the evaluation of
      patients presenting with pulmonary events after abciximab use.

PMID- 11451828
TI  - In patients with chronic atrial fibrillation and left ventricular systolic
      dysfunction, restoration of sinus rhythm confers substantial benefit.
AB  - STUDY OBJECTIVES: To evaluate the benefit of sinus rhythm (SR) restoration in
      patients with chronic controlled atrial fibrillation (AF) and left ventricular
      systolic dysfunction (LVSD). DESIGN: Prospective case-control study on the short
      term outcome (6 to 9 months) of clinical and echocardiographic variables
      following attempted cardioversion. SETTING: Outpatient clinic of a university
      hospital. PATIENTS: Fifteen men and 5 women, ranging in age from 40 to 76 years,
      who had chronic controlled (mean [+/- SD] ventricular rate, 82 +/- 10 beats/min)
      AF and left ventricular fractional shortening (LVFS) of < 28% at baseline.
      Control was provided by retrospective paired echocardiographic examinations of
      six AF patients, plus the study cases with potentially unsuccessful cardioversion
      or early recurrence of AF. INTERVENTIONS: Attempt to restore SR with amiodarone
      or electrical countershock. MEASUREMENTS AND RESULTS: Conversion was attained in
      17 patients, but AF recurred early in 4 patients, 3 of whom had proven ischemic
      LVSD. In the 13 patients with sustained SR, LVFS increased from 20 +/- 4% to 31
      +/- 6% (p < 0.0001). In contrast, no changes were detected in the control group
      (n = 13). This improvement was paralleled by decreases in left ventricular (LV)
      end-diastolic dimension (from 55 +/- 7 to 51 +/- 6 mm; p = 0.014), LV mass (from
      181 +/- 28 to 159 +/- 37 g; p = 0.015), and left atrial diameter (from 45 +/- 9
      mm to 42 +/- 7; p = 0.003). A marked decrease in heart rate (from 82 +/- 9 to 64
      +/- 5 beats/min; p < 0.0001) and a reduction in New York Heart Association
      functional class (from 2.3 +/- 0.9 to 1.2 +/- 0.4; p = 0.0007) also were observed
      in patients with sustained SR but not among subjects in the control group.
      CONCLUSIONS: Even when adequate control of the ventricular rate has been
      achieved, the LV function of patients with chronic AF greatly improves after
      restoration and maintenance of SR.

PMID- 11451829
TI  - Left superior vena cava persistence in patients undergoing pacemaker or
      cardioverter-defibrillator implantation: a 10-year experience.
AB  - OBJECTIVE: The persistence of a left superior vena cava (LSVC) has been observed
      in 0.3% of the general population as established by autopsy. In the adult
      population, it is an important anatomic finding if a left superior approach to
      the heart is considered. The aim of the study was to evaluate the prevalence of a
      LSVC in patients undergoing pacemaker (PM) and cardioverter-defibrillator (CD)
      implantation. DESIGN: We observed the prevalence of LSVC during a 10-year period;
      each patient undergoing PM or transvenous CD implantation received a left
      cephalic/left subclavian venous approach to the heart. With this technique, LSVC
      persistence is easily diagnosed during lead placement. RESULTS: A total of 1,139
      patients consecutively underwent PM implantation during 10 years: 4 patients had
      persistent LSCV (0.34%). Among 115 patients undergoing CD implantation, 2
      patients with LSVC (1.7%) were observed. Overall LSVC persistence was found in 6
      of 1,254 patients (0.47%). Two patients, one of whom had no right superior vena
      cava (RSVC), received a left-sided PM, whereas two other patients received right
      sided devices. Both CD patients received a left-sided active-can device: the
      first patient with a right-sided lead tunneled to the left pectoral pocket, as a
      result of poor catheter handling through the LSVC and coronary sinus, and the
      second patient with a screw-in lead from LSVC. Long-term follow-up of these
      patients (average +/- SD, 41 +/- 26 months) revealed absence of lead dislodgment
      and appropriate device function regardless of lead implantation site.
      CONCLUSIONS: Persistence of LSVC in adults undergoing PM/CD implantation is
      similar to that of the general population (0.47% in our study). The left-sided
      implant can be achieved by stylet shaping and by use of active fixation leads in
      most patients, with a reliable outcome at short term in addition to appropriate
      device performance at follow-up. Assessment of the RSVC is advisable when
      planning a right-sided implantation, since a minority of patients lacks this
      vessel.

PMID- 11451830
TI  - Dynamics of left ventricular diastolic filling during exercise: a Doppler
      echocardiographic study of boys 10 to 14 years old.
AB  - STUDY OBJECTIVE: Factors influencing diastolic filling of the left ventricle may
      serve as critical determinants of both maximal cardiac output and oxygen uptake.
      This study was conducted to assess diastolic filling dynamics of the left
      ventricle during progressive upright cycle exercise in children. METHODS: Twelve
      boys aged 10 to 14 years underwent cycle testing with determination of
      transmitral flow velocities and pressure gradients as well as cardiac stroke
      volume using Doppler echocardiography. RESULTS: Estimated diastolic filling
      period shortened from 0.479 +/- 0.043 s at rest to 0.138 +/- 0.015 s at peak
      exercise. The peak and mean transmitral pressure gradient rose fourfold from rest
      to peak exercise. Mitral flow volume per beat rose by only 40% and remained
      stable beyond mild-to-moderate intensity work. CONCLUSIONS: Increases in
      transmitral pressure gradient with exercise may serve principally to augment
      velocity of ventricular filling with the progressively shortening diastolic time
      period.

PMID- 11451831
TI  - Impact of menopause on the prevalence and severity of sleep apnea.
AB  - STUDY OBJECTIVES: To compare the prevalence and severity of sleep apnea between
      premenopausal and postmenopausal women, and to determine whether these
      differences are affected by the body mass index (BMI) and neck circumference.
      DESIGN: Cross-sectional study utilizing a sleep clinic patient database. SETTING:
      University hospital. PATIENTS: A total of 1,315 women, classified into
      premenopausal and postmenopausal groups based on age (< 45 years and > 55 years,
      respectively). MEASUREMENTS: Anthropometric measurements included height, weight,
      and neck circumference. Sleep measurements included full nocturnal
      polysomnography. Sleep apnea was defined as an apnea-hypopnea index (AHI) > 10/h.
      RESULTS: There were 797 premenopausal and 518 postmenopausal women. The latter
      group was more obese (mean +/- SE BMI, 32.2 +/- 0.4 kg/m(2) vs 30.2 +/- 0.4
      kg/m(2); p < 0.0001) and had larger neck circumference (37.1 +/- 0.2 cm vs 35.8
      +/- 0.2 cm; p < 0.0001). The prevalence of sleep apnea was greater in
      postmenopausal women than premenopausal women (47% vs 21%; chi(2) < 0.0001).
      There were proportionately more postmenopausal than premenopausal women in all
      ranges of apnea severity (AHI, 10 to 30/h, 30 to 50/h, and > 50/h).
      Postmenopausal women had a significantly higher mean AHI compared to
      premenopausal women (17.0 +/- 0.9/h vs 8.7 +/- 0.6/h; p < 0.0001); this
      significant difference persisted even after adjusting for BMI and neck
      circumference. CONCLUSION: There may be functional, rather than anatomic,
      differences in the upper airway between premenopausal and postmenopausal women,
      which may account for the observed differences in apnea prevalence and severity.

PMID- 11451832
TI  - Upper-airway collapsibility: measurements and sleep effects.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repetitive
      pharyngeal collapse during sleep. Several techniques have been proposed to assess
      the collapsibility of the upper airway in awake humans, but sleep-wake
      comparisons have rarely been attempted and there are few studies comparing OSA
      patients to control subjects. We sought to compare two collapsibility measurement
      techniques between normal and apneic subjects, and between wakefulness and sleep.
      DESIGN: We conducted three studies. First, we examined whether collapsibility
      assessed by negative pressure pulses (NPPs) during wakefulness reflected values
      during sleep in 21 normal subjects. Second, we determined in these normal
      subjects whether collapsibility during sleep assessed by NPPs was predictive of
      collapsibility measured by inspiratory resistive loading (IRL). Finally, we
      compared upper-airway collapsibility between apnea patients (n = 22) and normal
      volunteers (n = 38) during wakefulness by NPPs. SETTING: Clinical and research
      laboratories at the Brigham and Women's Hospital. PARTICIPANTS: Two populations
      of normal subjects (n = 21 and n = 38) and OSA patients (n = 22). MEASUREMENTS
      AND RESULTS: Collapsibility during wakefulness, as measured by NPPs, correlated
      significantly with collapsibility during sleep (r = 0.62; p = 0.003). There was
      also a significant correlation between the two measures of collapsibility (IRL
      and NPP) during sleep (r = 0.53; p = 0.04). Both measures revealed a significant
      increase in pharyngeal collapsibility during sleep as compared to wakefulness.
      Finally, apnea patients had significantly greater pharyngeal collapsibility than
      control subjects during wakefulness (p = 0.017). CONCLUSIONS: These data suggest
      that upper-airway collapsibility measured during wakefulness does provide useful
      physiologic information about pharyngeal mechanics during sleep and demonstrates
      clear differences between individuals with and without sleep apnea.

PMID- 11451833
TI  - Mandibular advancement device in patients with obstructive sleep apnea : long
      term effects on apnea and sleep.
AB  - STUDY OBJECTIVES: To evaluate the long-term effects on apneas and sleep and the
      tolerability of a mandibular advancement device in patients with obstructive
      sleep apnea. DESIGN: Prospective study. SETTING: Department of Respiratory
      Medicine, University Hospital, Umea, Sweden. PATIENTS: Thirty-three consecutively
      treated patients. INTERVENTIONS: Individually adjusted mandibular advancement
      devices. MEASUREMENTS AND RESULTS: Polysomnographic sleep recordings on 1 night
      without the device and 1 night with the device were performed after 0.7 +/- 0.5
      years (mean +/- SD) and after 5.2 +/- 0.4 years from the start of treatment.
      Nineteen of the 33 patients experienced a short-term satisfactory treatment
      result with an apnea-hypopnea index of < 10 events per hour and a satisfactory
      reduction in snoring. Fourteen patients were regarded as being insufficiently
      treated with the device. Seventeen of the short-term satisfactorily treated
      patients (90%) and 2 of the remaining patients continued treatment on a long-term
      basis. The apnea-hypopnea index was reduced by the device from 22 +/- 17 to 4.9
      +/- 5.1 events per hour (p < 0.001) in these 19 long-term treatment patients,
      which did not differ from what was found at the short-term follow-up visits in
      these patients. Patients with their devices replaced or adjusted experienced a
      better long-term effect than patients still using their original devices (p <
      0.05). CONCLUSIONS: The long-term effect and tolerability of a mandibular
      advancement device are good in patients who are recommended the treatment on the
      basis of a short-term sleep recording, provided that the device is continuously
      adjusted or replaced with a new one when needed. A short-term follow-up is
      valuable in the selection of patients who will benefit from long-term treatment
      with a mandibular advancement device.

PMID- 11451834
TI  - Determinants of continuous positive airway pressure compliance in a group of
      Chinese patients with obstructive sleep apnea.
AB  - OBJECTIVE: To assess continuous positive airway pressure (CPAP) compliance and
      factors associated with CPAP compliance among Chinese patients with obstructive
      sleep apnea (OSA). DESIGN: A prospective study of 112 consecutive patients with
      newly diagnosed OSA commencing CPAP treatment. SETTING: A university teaching
      hospital. MEASUREMENTS AND RESULTS: The following factors were evaluated for any
      correlation with objective CPAP compliance (effective mask pressure [hours per
      day]) at 1 month and 3 months: age, baseline apnea-hypopnea index (AHI), common
      OSA symptoms, minimum arterial oxygen saturation (SaO(2)), mean SaO(2), arousal
      index (AI), Epworth sleepiness scale (ESS), education level, CPAP levels,
      satisfaction with CPAP, side effects, and machine cost. There were 101 male and
      11 female patients, with a mean (+/- SD) age of 45.6 +/- 1.2 years; body mass
      index, 29.3 +/- 5.2 kg/m(2); AI, 60 +/- 18/h; AHI, 48 +/- 24/h; minimum SaO(2) of
      70 +/- 17%; and mean SaO(2) of 86 +/- 7%. ESS fell from 12.9 +/- 4.0 (baseline)
      to 5.2 +/- 4.7 at 3 months (p < 0.001). Objective CPAP compliance was 5.4 +/- 1.6
      h/d and 5.3 +/- 1.6 h/d, while 75% and 72% of our patients were using CPAP
      objectively for > or = 4 h/d and at least 70% of the nights per week at 1 month
      and 3 months, respectively. Following univariate analysis of variance, a high
      baseline AHI (p = 0.006 and p = 0.004) was associated with higher objective CPAP
      compliance at 1 month and 3 months, respectively. CONCLUSION: CPAP usage and
      compliance were high in this patient population. A high baseline AHI was the only
      significant independent predictor of better CPAP compliance.

PMID- 11451835
TI  - Pulmonary fungal infection: emphasis on microbiological spectra, patient outcome,
      and prognostic factors.
AB  - STUDY OBJECTIVES: To investigate the microbiological spectra, patient outcome,
      and prognostic factors of pulmonary fungal infection. DESIGN: The medical and
      microbiological records of patients with pulmonary fungal infection were
      retrospectively analyzed. SETTING: A university-affiliated tertiary medical
      center. PATIENTS AND METHODS: From January 1988 to December 1997, all cases of
      pulmonary fungal infection were reviewed. The criteria for inclusion were obvious
      lung lesion shown on chest radiographs and one of the following: (1) the presence
      of fungi in or isolation of fungi from the biopsy specimen of open thoracotomy,
      thoracoscopy, transbronchial lung biopsy, or ultrasound-guided percutaneous
      needle aspiration/biopsy; or (2) isolation of fungi from pleural effusion or
      blood, with no evidence of extrapulmonary infection. RESULTS: A total of 140
      patients were included. Ninety-four cases of pulmonary fungal infection (67%)
      were community acquired. The most frequently encountered fungi were Aspergillus
      species (57%), followed by Cryptococcus species (21%) and Candida species (14%).
      There were 72 patients with acute invasive fungal infection, with a mortality
      rate of 67%. Multivariate logistic regression analysis showed that nosocomial
      infection (p = 0.014) and respiratory failure (p = 0.001) were significantly and
      independently associated with death of acute invasive fungal infection.
      CONCLUSIONS: Pulmonary fungal infection of community-acquired origins is becoming
      a serious problem. It should be taken into consideration for differential
      diagnosis of community-acquired pneumonia. Furthermore, acute invasive fungal
      infection is associated with a much higher mortality rate for patients with
      nosocomial infection or complicating respiratory failure. Early diagnosis with
      prompt antifungal therapy, or even with surgical intervention, might be warranted
      to save patients' lives.

PMID- 11451836
TI  - Clinical evaluation of the management of community-acquired pneumonia by general
      practitioners in France.
AB  - STUDY OBJECTIVES: To evaluate the management of community-acquired pneumonia
      (CAP) by general practitioners (GPs) in terms of clinical efficiency and
      adherence to official recommendations. DESIGN: Prospective cohort study. SETTING:
      Community-based study from 11 French counties. PATIENTS: Adult patients
      clinically suspected of having CAP who were seen by GPs were included after
      confirmation of the presence of an infiltrate on chest radiographs. INTERVENTION:
      The management of the patients was left to the discretion of the GP. MEASUREMENTS
      AND RESULTS: One hundred thirty patients were included in the study, and 13
      patients (10%) were immediately hospitalized because of the severity of the
      pneumonia. The remaining 117 patients were treated as outpatients: 108 of 117
      patients (92%) were cured, and 9 patients were subsequently hospitalized because
      of the failure of ambulatory treatment. Diagnostic error (n = 6) rather than
      antibiotic failure (n = 3) was the most frequent cause of the failure of
      ambulatory treatment. Only 40% of the patients received an initial antibiotic
      treatment that was in agreement with French recommendations. However, the rate of
      antibiotic failure leading to hospitalization was low (3 of 117 patients; 2.6%)
      and similar for patients treated or not according to recommendations (p > 0.5).
      Overall, five patients (4%) died; all deaths occurred during hospitalization and
      were related to the severity of the underlying disease but not to the choice of
      antibiotic treatment. CONCLUSIONS: The management of CAP by GPs was clinically
      effective despite a poor adherence to official recommendations. Our results
      suggest that adequate assessment of severity rather than adherence to
      recommendations for antibiotic treatment had an impact on clinical outcome of CAP
      managed by GPs.

PMID- 11451837
TI  - Paradoxical worsening of tuberculosis in HIV-infected persons.
AB  - OBJECTIVE: To determine the incidence of paradoxical worsening of tuberculosis
      (TB) in HIV-infected persons. DESIGN: Observational cohort study. SETTING:
      Public, urban TB clinic. PATIENTS: HIV-infected persons treated for TB between
      January 1, 1996, and December 31, 1999, and followed through June 30, 2000.
      INTERVENTION: Patients received standard anti-TB therapy. Antiretroviral therapy
      was provided by primary medical providers. Patients receiving antiretroviral
      therapy were given nucleoside reverse transcriptase inhibitors alone or highly
      active antiretroviral therapy (HAART; nucleoside reverse transcriptase inhibitors
      in combination with a protease inhibitor or a nonnucleoside reverse transcriptase
      inhibitor). MAIN OUTCOME MEASURE: Paradoxical worsening of TB. RESULTS: There
      were 82 TB cases in 76 patients. Paradoxical worsening was identified in 6 of 82
      cases (7%; 95% confidence interval, 3 to 15%). Paradoxical worsening occurred in
      3 of 28 cases (11%) in patients receiving HAART and in 3 of 44 cases (7%) in
      patients not receiving antiretroviral therapy (p = 0.67). Cases complicated by
      paradoxical worsening were more likely to have both pulmonary and extrapulmonary
      disease at initial diagnosis than cases without paradoxical worsening (83% vs
      24%; p = 0.006). TB relapse occurred in 2 of 6 cases (33%) in patients with
      paradoxical worsening and in 4 of 76 cases (5%) in patients without paradoxical
      worsening (p = 0.06). CONCLUSIONS: Paradoxical worsening of TB occurred less
      frequently than in previous reports and was not associated with HAART.
      Paradoxical worsening also appeared to be associated with an increased risk of TB
      relapse. Further studies are warranted to better characterize the risk factors
      for paradoxical worsening and the appropriate duration of anti-TB therapy in
      patients in whom it occurs.

PMID- 11451838
TI  - Centrilobular nodules correlate with air trapping in diffuse panbronchiolitis
      during erythromycin therapy.
AB  - BACKGROUND: Low-dose erythromycin therapy improves airflow limitation and airway
      inflammation in patients with diffuse panbronchiolitis (DPB). However, to our
      knowledge there has been no study to determine whether physiologic improvement
      during erythromycin therapy correlates with radiologic findings. STUDY OBJECTIVE:
      To clarify whether improvement in pulmonary function correlates with specific
      changes on chest CT. DESIGN: The relationship between five CT findings and five
      pulmonary function parameters was evaluated before and 3 months after low-dose
      erythromycin therapy in 24 patients with DPB retrospectively. RESULTS: After
      erythromycin therapy, the predicted percentage of vital capacity (%VC; 87.0 +/-
      3.07% vs 98.9 +/- 3.39%; p = 0.00006) and 50% of the maximum midexpiratory flow
      rate of FVC (1.41 +/- 0.26 L/s vs 1.61 +/- 0.27 L/s; p = 0.03) significantly
      increased, and the residual volume/total lung capacity ratio (RV/TLC%; 44.5 +/-
      1.93% vs 40.7 +/- 1.83%; p = 0.0019) significantly decreased, but the FEV(1) to
      FVC ratio and 25% of the maximum expiratory flow rate of FVC did not. In five CT
      findings, centrilobular nodules (3.7 +/- 0.4 vs 1.5 +/- 0.3; p = 0.0001),
      peripheral bronchiolar wall thickness (3.8 +/- 0.3 vs 2.6 +/- 0.4; p = 0.0007),
      and peripheral bronchiolectasis (2.8 +/- 0.3 vs 2.2 +/- 0.4; p = 0.0058) had
      significantly improved, whereas low attenuation area and central bronchiectasis
      had not. There were positive correlations of improved scores of centrilobular
      nodules with improved %VC (r = 0.58, p = 0.0062) and RV/TLC% (r = 0.64, p =
      0.0022). CONCLUSIONS: Decreased air trapping in DPB correlates with an
      improvement of centrilobular nodules, which reflects the obstructive lesions of
      bronchioles during the erythromycin therapy.

PMID- 11451839
TI  - Efficacy of recombinant human deoxyribonuclease I in the hospital management of
      respiratory syncytial virus bronchiolitis.
AB  - OBJECTIVE: To evaluate the effect of recombinant human deoxyribonuclease I
      (rhDNase) in shortening the length of the hospitalization and improving the chest
      radiographs (CXRs) in hospitalized infants with respiratory syncytial virus (RSV)
      infection as a result of its mucolytic properties. METHODS: Randomized, double
      blind, placebo-controlled investigation of 75 patients with RSV bronchiolitis.
      The study was conducted at the University of Michigan Medical Center and St.
      Joseph Mercy Hospital, both in Ann Arbor, MI. RESULTS: The respiratory rate,
      wheezing, and retraction difference scores, obtained by subtracting the hospital
      discharge score from the corresponding hospital admission score, show no
      difference between the two groups, but the CXR difference scores show that the
      rhDNase group improved by 0.46 while the placebo group worsened by 0.60 (p <
      0.001). Analysis of covariance for the hospital discharge CXR score after
      adjusting for the hospital admission score for both groups was done. There was a
      difference in scores between the two groups, with adjusted mean for the study
      group of 2.03, and 2.76 for the placebo group (p < 0.001). Paired t test
      statistics in each of the two groups were computed. For the placebo group, the
      mean increase of 0.60 was significant (p = 0.02), and the mean decrease of 0.46
      for the rhDNase group was also significant (p = 0.02). A one-way analysis of
      covariance with the hospital discharge CXR scores as the dependent variable and
      the hospital admission score as the covariate showed that there was a significant
      difference between the groups (p = 0.01). CONCLUSION: In patients with RSV
      bronchiolitis, there was significant improvement in the CXRs with the use of
      rhDNase compared to significant worsening in the placebo group. To our knowledge,
      this is the first report of the use of rhDNase to treat RSV bronchiolitis.

PMID- 11451840
TI  - Outcome of patients with idiopathic pulmonary fibrosis admitted to the ICU for
      respiratory failure.
AB  - STUDY OBJECTIVES: To analyze the outcome of acute respiratory failure (ARF) in
      patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the benefits
      of invasive and noninvasive mechanical ventilation (MV). DESIGN: Retrospective
      study. SETTING: University hospital. PATIENTS: Fifteen consecutive patients with
      IPF referred to the ICU for ARF between January 1989 and June 1998. MEASUREMENTS
      AND RESULTS: Fifteen patients (mean +/- SD age, 64 +/- 10 years) were included.
      Eight patients had clinical, functional, and radiologic features of IPF, and the
      remaining seven patients also had biopsy specimen-proven IPF. The mean duration
      between diagnosis of IPF and admission to the ICU was 26.5 +/- 28 months. At the
      time of ICU admission, mean arterial blood gas levels were as follows:
      PaO(2)/fraction of inspired oxygen, 113 +/- 95; pH, 7.32 +/- 0.10; and PaCO(2),
      55 +/- 21 mm Hg. All patients received MV; 12 patients required tracheal
      intubation, either at the time of ICU admission (n = 10) or after failure of
      noninvasive ventilation (NIV; n = 2); and 3 patients only received NIV. Three of
      the five patients receiving NIV died of respiratory failure. Eleven patients died
      in the ICU, either from hypoxemia (n = 8) or from septic shock (n = 3). Four
      patients were discharged alive from the ICU, and two of them died shortly
      thereafter. CONCLUSION: The outcome of patients with IPF referred to the ICU for
      ARF was very poor and not improved by MV. Without a clearly identified reversible
      cause of ARF, these patients should not benefit from admission to the ICU.

PMID- 11451841
TI  - Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring
      mechanical ventilation for acute respiratory failure.
AB  - STUDY OBJECTIVE: To evaluate the beneficial effect of mechanical ventilation (MV)
      in patients with idiopathic pulmonary fibrosis (IPF) who develop acute
      respiratory failure (ARF), with special emphasis on prognosis. DESIGN:
      Retrospective study. SETTING: Ten-bed respiratory ICU that is a part of a
      respiratory department actively involved in lung transplantation (LTx). PATIENTS:
      From 1991 to 1999, 23 patients (mean age, 52.9 years; range, 21 to 82 years) with
      IPF required MV for ARF. At admission to the ICU, 16 patients were potential
      candidates for LTx, with 5 patients already on the waiting list. MEASUREMENTS AND
      RESULTS: Survival and gas exchange under MV were assessed. The precipitating
      cause of ARF was also analyzed. With the exception of 1 patient who successfully
      received a single-lung transplant 6 h after initiation of MV, all the remaining
      22 patients died while receiving MV (median survival, 3 days; range, 1 h to 60
      days). The duration of MV correlated positively with baseline vital capacity
      (percent predicted) (R = 0.54; p = 0.01) and baseline total lung capacity
      (percent predicted) (R = 0.71; p < 0.001), and correlated negatively with
      baseline PaCO(2) (R = - 0.47; p = 0.03) and the duration of evolution of IPF (R =
      -0.50; p = 0.01). Duration of MV did not correlate with the duration of
      immunosuppressive therapy (R = - 0.24; p = 0.27) or duration of oxygen therapy (R
      = - 0.32; p = 0.14) prior to admission. The precipitating cause of ARF was most
      often not identified. CONCLUSIONS: Our data support the general belief that MV
      does not benefit IPF patients presenting with ARF. Initiation of MV in IPF
      patients is thus questionable and should, in our opinion, be restricted to
      patients in whom LTx can be performed within a few days after initiation of MV.

PMID- 11451842
TI  - Prevention of nosocomial urinary tract infection in ICU patients: comparison of
      effectiveness of two urinary drainage systems.
AB  - STUDY OBJECTIVES: To determine whether the rate of acquisition of bacteriuria
      differs between the use of a complex closed drainage system (CCDS) with a
      preattached catheter, antireflux valve, drip chamber, and povidone-iodine
      releasing cartridge, and a two-chamber open drainage system (TCOS) in ICU
      patients. DESIGN: Prospective, nonrandomized, controlled trial. SETTING:
      Medical/surgical/trauma ICU in a university hospital. PATIENTS: Two hundred
      twenty-four ICU patients requiring an indwelling urinary catheter. INTERVENTION:
      We compared the rate of acquisition of bacteriuria in two groups of consecutive
      patients (n = 113 and n = 111, respectively) who underwent bladder
      catheterization with a TCOS during the first 6 months and with a CCDS during the
      next 6 months. Urinary catheters were managed by a team of trained nurses
      following the same written protocol. No prophylactic antibiotics were
      administered, either during management of catheter placements or catheter
      withdrawal, but 75% of patients received one or more antimicrobial medications
      for treatment of infected sites other than the urinary tract. Urine samples were
      obtained weekly for the duration of catheterization and within 24 h after
      catheter removal, and each time symptoms of urinary infection were suspected.
      Only patients who required an indwelling catheter for > 48 h were evaluated.
      MEASUREMENTS AND RESULTS: There was no statistical difference in the rate of
      bacteriuria between the two groups. Bacteriuria occurred in 11.5% and 13.5% of
      patients, and was diagnosed on day 14 +/- 8 and 13 +/- 9 of catheterization (mean
      +/- SD) for the TCOS and the CCDS, respectively. A CCDS cost $3 (US dollars) more
      than the TCOS. CONCLUSIONS: To our knowledge, this is the first study to compare
      the effectiveness of a TCOS and a CCDS in ICU patients. No differences were noted
      between the two systems (alpha = 0.05). The higher cost of a CCDS is not
      justified for ICU patients.

PMID- 11451843
TI  - Analysis of early deaths after isolated lung transplantation.
AB  - STUDY OBJECTIVES: To determine the causes of death in patients dying within 30
      days after lung transplantation at the University of Florida, to assess the
      importance of several diagnostic modalities for determining the causes of their
      decline, and to construct an algorithm for the evaluation of patients with severe
      respiratory compromise occurring early after lung transplantation. DESIGN:
      Retrospective review of medical records and pathology slides from all patients
      dying within 30 days after lung transplantation, and biopsy specimen diagnoses
      from all lung allograft recipients at the University of Florida. PATIENTS: Nine
      deaths occurred during the first 30 days after transplantation among 117 patients
      undergoing 123 isolated lung transplantation operations. RESULTS: Infections
      accounted for the greatest number of deaths (bacterial pneumonia, four patients;
      catheter-related bacteremia, one patient). Persistent pneumonia confirmed by
      biopsy specimen was usually accompanied by histologic manifestations of acute
      cellular rejection and was associated with poor patient outcome (ie, death or
      subsequent development of bronchiolitis obliterans syndrome). In two patients,
      antibody-mediated rejection either was the immediate cause of death (hyperacute
      rejection, one patient) or preceded a fatal case of pneumonia (accelerated
      antibody-mediated rejection, one patient). Other causes of death included hypoxic
      ischemic encephalopathy secondary to an intraoperative cardiac arrest (one
      patient), pulmonary venous thrombosis with bacterial colonization of the
      thrombotic material (one patient), and ischemic reperfusion injury (one patient).
      In most patients, more than one type of diagnostic technique was needed to
      ascertain the cause of the catastrophic decline. CONCLUSIONS: The causes of early
      posttransplant death in our patient group included infections, antibody-mediated
      rejection, hypoxic-ischemic encephalopathy secondary to cardiac arrest, pulmonary
      venous thrombosis, and ischemic reperfusion injury. Because these processes often
      demonstrate overlapping clinical and morphologic features requiring multiple
      diagnostic techniques for resolution, a systematic multimodality approach to
      diagnosis is advantageous for determining the causes of decline in individual
      patients and for estimating the incidences of the different causes of early graft
      and patient loss in the lung transplant population.

PMID- 11451844
TI  - The role of laser-induced fluorescence in myocardial tissue characterization: an
      experimental in vitro study.
AB  - OBJECTIVE: The fluorescence of tissue when stimulated by a laser beam is a well
      known phenomenon. The resulting emission spectra depend on the biochemical and
      structural composition of the tissue. In this study, we examined the spectra of
      laser-induced fluorescence emitted by myocardial tissue. METHODS: We used an
      argon-ion laser to stimulate the myocardium of 20 intact sheep hearts. For each
      spectral emission, we calculated the intensity in specific regions in order to
      characterize the spectra and to reveal intercavitary and intracavitary
      morphologic differences. RESULTS: The statistical analysis showed significant
      differences in the emission spectra intensity between atria and ventricles. The
      intensity was higher in the atria than in the ventricles (p < 0.001). The atrial
      emission spectra were morphologically different from those of the ventricles.
      There was no difference in the intensity or morphology of emission spectra within
      each chamber. All measurements showed good reproducibility after a short period
      of time. CONCLUSIONS: Laser-induced fluorescence of myocardial tissue seems to
      have the characteristics necessary for tissue recognition. This might prove
      useful in identifying cardiomyopathies and transplant rejection, as well as for
      myocardial mapping, assisting electrophysiologists in discovering fibrotic
      arrhythmogenic foci.

PMID- 11451845
TI  - Effect of age on respiratory defense mechanisms: pulmonary bacterial clearance in
      Fischer 344 rats after intratracheal instillation of Listeria monocytogenes.
AB  - STUDY OBJECTIVES: To examine the lung defense mechanisms of both young and aged
      rats before and after pulmonary challenge with a bacterial pathogen. DESIGN: Male
      Fischer 344 rats, either 2.5 months or 20 months of age, were intratracheally
      inoculated with 5 x 10(3), 5 x 10(4), or 5 x 10(5) Listeria monocytogenes, and
      the effects on mortality, lung inflammation, pulmonary bacterial clearance,
      alveolar macrophage (AM) function, and T-lymphocyte characterization were
      determined. MEASUREMENTS AND RESULTS: In noninfected control animals, the older
      rats had lower numbers of AMs on lavage and a lower percentage of total T, CD4+,
      and CD8+ cells. No difference was observed between noninfected young and old rats
      in AM function, assessing both chemiluminescence and nitric oxide (NO)
      production. After bacterial challenge, aged rats exhibited an increase in
      mortality, pulmonary infection, and edema, and lung lesions, which were more
      extensive than those observed in the younger rats. Interestingly, AM
      chemiluminescence was enhanced, while AM NO, a highly important antibacterial
      defense product, was abrogated in the aged rats as compared to the young rats.
      CONCLUSIONS: This study demonstrated that advanced age is associated with
      alterations in lung defense mechanisms and increased susceptibility to pulmonary
      bacterial infection marked by elevated mortality, slowed pulmonary bacterial
      clearance, and altered AM function, specifically a decrease in NO production.
      These observations are indicative of reduced pulmonary defense function in an
      older population of rats.

PMID- 11451846
TI  - Lessons from a proficiency testing event for acid-fast microscopy.
AB  - OBJECTIVES: To evaluate the routine performance and the technical parameters of
      different acid-fast staining methods: Kinyoun, Ziehl-Neelsen (ZN), auramine, and
      auramine-rhodamine. DESIGN AND PARTICIPANTS: The performance of 167 laboratories
      was analyzed using prestained and unstained slides. SETTING: Laboratories holding
      New York State permits. RESULTS: The results revealed that Kinyoun's cold carbol
      fuchsin method is inferior to both the ZN and fluorochrome (auramine and/or
      auramine-rhodamine) methods. Even though 91% of the participants used commercial
      staining kits, the study identified unexpected errors concerning the
      concentration of carbol fuchsin, time for staining and counterstaining, and the
      concentration of acid alcohol for decolorization, which may significantly
      influence the sensitivity. Besides these findings, the present study showed that
      the examination of < 300 view fields may also decrease the sensitivity of acid
      fast microscopy. In addition, we found that the sensitivity and specificity of
      the ZN and fluorochrome methods are comparable if the procedural standards are
      followed. CONCLUSIONS: The strict and ongoing quality control of the "simple to
      perform" acid-fast microscopy and the immediate review of commercially available
      staining kits are necessary. Because of the rapidity of the fluorochrome method,
      laboratories with large specimen numbers should use this technique. In all other
      cases, the ZN method should be used. Moreover, all clinicians should be aware of
      the method of acid-fast microscopy used and the proficiency of the laboratory in
      performing the assay.

PMID- 11451847
TI  - Alternative mechanisms for long-acting beta(2)-adrenergic agonists in COPD.
AB  - beta(2)-Adrenergic agonists are commonly used as bronchodilators to treat
      patients with COPD. In addition to prolonged bronchodilation, long-acting beta(2)
      agonists (LABAs) exert other effects that may be of clinical relevance. These
      include inhibition of airway smooth-muscle cell proliferation and inflammatory
      mediator release, as well as nonsmooth-muscle effects, such as stimulation of
      mucociliary transport, cytoprotection of the respiratory mucosa, and attenuation
      of neutrophil recruitment and activation. This review details the possible
      alternative mechanisms of action of the LABAs, salmeterol and formoterol, in
      COPD.

PMID- 11451848
TI  - Rapid alveolar epithelial fluid clearance following lung lavage in pulmonary
      alveolar proteinosis.
AB  - STUDY OBJECTIVE: To measure the in vivo rate of alveolar epithelial fluid
      clearance of the human lung in patients with pulmonary alveolar
      phospholipoproteinosis (PAP). DESIGN: Prospective clinical study. SETTING: The
      medical-surgical ICUs of a university teaching hospital. PATIENTS: Four patients
      with idiopathic PAP requiring therapeutic lung lavage. INTERVENTIONS: Large
      volume lung lavage with isotonic saline solution using fiberoptic bronchoscopy
      followed by serial sampling of alveolar fluid using a wedged bronchial catheter.
      MEASUREMENTS AND RESULTS: The rate of alveolar epithelial fluid clearance was
      calculated by measuring the concentration of protein in sequential samples.
      Alveolar epithelial fluid clearance over the first hour after lung lavage was 53
      +/- 14% (mean +/- SD). Sequential samples in two patients indicated a sustained
      high rate of clearance over several hours. Plasma and alveolar fluid epinephrine
      levels were in the normal range in two patients. CONCLUSIONS AND SIGNIFICANCE:
      Alveolar fluid clearance is rapid after lung lavage in patients with PAP and
      appears to be driven by catecholamine-independent mechanisms. The rapid rate of
      alveolar epithelial fluid transport explains why patients with PAP tolerate large
      volume lung lavage.

PMID- 11451849
TI  - Is amiodarone an underrecognized cause of acute respiratory failure in the ICU?
AB  - Amiodarone is a commonly used anti-arrhythmic agent, with well-recognized chronic
      toxicity. Less well known is amiodarone's potential to cause acute lung damage,
      which can be severe or, occasionally, life-threatening. Lungs that have already
      been exposed to physical insults, such as the lungs of patients undergoing
      cardiac surgery, are particularly susceptible to acute pulmonary toxicity (APT).
      Unfortunately, cardiac surgery is one of the clinical scenarios in which
      amiodarone is most commonly used. After reviewing the data, and even in the
      context of difficulties and discrepancies in the existing literature, we contend
      that there is sufficient evidence of amiodarone's potentially serious side-effect
      profile in surgical ICU patients to advise continued caution in its use with this
      severely ill patient group. We suggest that amiodarone has a potentially
      important, though underrecognized, role in inducing an APT/ARDS in some patients,
      such as those undergoing cardiac surgery. We also provide a hypothesis to explain
      the mechanism by which amiodarone causes lung damage.

PMID- 11451850
TI  - Low compliance with national standards for cardiovascular emergency preparedness
      at health clubs.
AB  - There is heightened concern that older adults and individuals with occult or
      known heart disease are exercising at fitness facilities that do not provide
      adequate cardiovascular screening and emergency procedures, as outlined in
      contemporary recommendations. To evaluate adherence to these standards, we
      surveyed 122 randomly chosen fitness clubs in Ohio (53% response rate; n = 65)
      that included > 110,000 total members. Special programs for older adults, cardiac
      patients, or both, were offered at 52% of these clubs. More than one fourth of
      the clubs (28%) failed to employ pre-entry screening to identify members with
      signs, symptoms, or history of cardiovascular disease, even though 17% reported
      one or more cardiovascular emergencies (ie, acute myocardial infarction, sudden
      cardiac death, or both) in their facility during the past 5 years. Moreover, a
      majority of the clubs (53%) had no written emergency response plan and 92% failed
      to conduct emergency response drills as described in published national
      standards. Only 3% of the centers reported having automated external
      defibrillators. These findings indicate that staff at public fitness facilities
      must work to identify members with signs, symptoms, or history of cardiovascular
      disease and prepare for prompt and appropriate responses to cardiovascular
      emergencies as described in contemporary national recommendations. Such risk
      management procedures may reduce exercise-related cardiovascular events among the
      escalating number of moderate-to-high-risk adults who are being mainstreamed into
      health and fitness facilities.

PMID- 11451851
TI  - Thoracoscopy or CT-guided biopsy for residual intrathoracic masses after
      treatment of lymphoma.
AB  - BACKGROUND: An intrathoracic mass persists after completion of treatment in 20%
      of the patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma
      (NHL). Gallium scan and positron emission tomography allow for diagnosis in most
      cases. However, in some patients, a pathologic examination of the residual mass
      (RM) is required. The aim of this study was to evaluate the results of a
      thoracoscopic approach for intrathoracic RM, as compared with image-guided
      biopsies. PATIENTS AND METHODS: From 1996 to 1998, 29 consecutive patients
      treated for NLH (n = 11) or HD (n = 18) were referred either to radiology (group
      R; n = 8) or to surgery (group S; n = 21) for biopsy of an intrathoracic RM.
      There were 13 male and 16 female patients ranging in age from 15 to 56 years
      (mean, 32 years). The reason for a biopsy was the inability to determine the
      nature of the RM by means of radiologic examination or scintigraphy. Biopsy was
      defined as successful when (1) residual lymphoma was found in the specimen, or
      (2) benign tissue was found and the patient remained disease-free after a minimal
      follow-up period of 12 months. A biopsy was defined as a failure when a local
      recurrence occurred in a patient with a diagnosis of benign lesion. RESULTS: No
      significant procedure-related complications occurred in either group. The mean
      follow-up was 26 months (range, 13 to 72 months). In group R, residual lymphoma
      was found in only one patient. In group S, residual lymphoma was found in seven
      patients (p = 0.5). In the seven patients of group R with a diagnosis of benign
      mediastinal lesion, two patients had a local recurrence and one had a recurrence
      within the abdomen. In the 15 patients of group S in whom no residual disease was
      found, 1 patient had an intrathoracic recurrence (p = 0.5) while 2 patients had
      recurrence in a remote site. CONCLUSION: Despite the limited number of patients
      in this series, results suggest that a thoracoscopic approach yields better data
      than image-guided biopsies.

PMID- 11451852
TI  - Gait disturbance, confusion, and coma in a 93-year-old blind woman.

PMID- 11451853
TI  - A 53-year-old man with hemoptysis.

PMID- 11451854
TI  - Thromboembolic prophylaxis in total joint replacement.

PMID- 11451855
TI  - Does sildenafil also improve breathing?
AB  - Sildenafil is being used by a number of patients with erectile dysfunction. Some
      of these patients also may have concomitant COPD. The effect of sildenafil on
      lung function is not known. Two patients with severe COPD and erectile
      dysfunction reported that their dyspnea improved when they took oral sildenafil
      for erectile dysfunction. Spirometry performed in these patients revealed an
      improvement in FEV(1) by 24% and 12%. This suggests that, in COPD patients, oral
      sildenafil does not have any deleterious effect on pulmonary function, and in
      some patients it may produce a modest improvement in FEV(1).

PMID- 11451856
TI  - Cervical emphysema, pneumomediastinum, and pneumothorax following self-induced
      oral injury: report of four cases and review of the literature.
AB  - Spontaneous rupture of the pulmonary alveoli after a sudden increase in intra
      alveolar pressure is a common cause of pneumomediastinum, which is usually seen
      in healthy young men. Other common causes are traumatic and iatrogenic rupture of
      the airway and esophagus; however, pneumomediastinum following cervicofacial
      emphysema is much rarer and is occasionally found after dental surgical
      procedures, head and neck surgery, or accidental trauma. We present four cases of
      subcutaneous emphysema and pneumomediastinum with two secondary pneumothoraces
      after self-induced punctures in the oral cavity. They constitute an uncommon
      clinical entity that, to our knowledge, has not been reported in the literature.
      Its radiologic appearance, clinical presentation, and diagnosis are described.

PMID- 11451857
TI  - Compressive neuropathy of the brachial plexus and long thoracic nerve: a rare
      complication of heparin anticoagulation.
AB  - We present a case of a 69-year-old woman who developed brachial plexopathy and
      long thoracic nerve palsy secondary to compression from a hematoma while
      receiving heparin therapy for the treatment of a stroke. The patient was treated
      conservatively with discontinuation of heparin and had complete resolution of her
      compressive neuropathy. This is the first report of a patient with long thoracic
      nerve palsy with a brachial plexopathy complicating anticoagulation. We review
      the literature on hematoma-induced compressive neuropathies and treatment
      options. Our review concludes by emphasizing the importance of clinical judgment
      in determining the best therapeutic modality.

PMID- 11451858
TI  - Spontaneous hemomediastinum complicating steroid-induced mediastinal lipomatosis.
AB  - Spontaneous hemomediastinum is a rare event, occurring in association with
      bleeding disorders, intratumoral bleeding, or following an abrupt increase in
      intrathoracic pressure. We report the case of a patient with systemic lupus
      erythematosus, nephrotic syndrome, and renal failure, in whom mediastinal
      lipomatosis (ML) developed following increased corticosteroid therapy.
      Anticoagulant therapy likely precipitated a massive spontaneous hemomediastinum
      secondary to diffuse hemorrhage of mediastinal fat, which required emergency
      decompressive surgery. Steroid-induced ML is common and usually well tolerated,
      but clinicians should be aware of its potential risk of bleeding when associated
      with anticoagulant therapy. This case further emphasizes the bleeding
      complications of treatment with low-molecular-weight heparin in patients with
      renal failure.

PMID- 11451859
TI  - Pleuropulmonary disease due to pergolide use for restless legs syndrome.
AB  - Pergolide is an ergot-derived dopamine agonist used in Parkinson's disease and,
      increasingly, in restless legs syndrome. We report a patient with a 2.5-year
      history of weight loss, pleuropulmonary fibrosis, and exudative pleural effusion
      that developed insidiously while taking this medication. The extensive and
      invasive workup that preceded the diagnosis highlights the difficulty in
      attributing such a process to a drug reaction. This is the second report of such
      a reaction to pergolide, which is one of the increasing number of ergot-derived
      compounds in common clinical use.

PMID- 11451860
TI  - Treatment of a solitary pulmonary sarcoidosis mass by CT-guided direct
      intralesional injection of corticosteroid.
AB  - A case is reported of 38-year-old woman with chest pain attributed to a left lung
      sarcoidosis mass. The mass failed to diminish and symptoms failed to resolve with
      systemic corticosteroid therapy. CT-guided direct intralesional transthoracic
      injection of dexamethasone resulted in resolution of the patient's symptoms and a
      dramatic reduction in the size of the mass within 2 months.

PMID- 11451861
TI  - Home oxygen requalification.

PMID- 11451862
TI  - Fluoroquinolone pharmacodynamics and efficacy.

PMID- 11451863
TI  - Incidence of pleuropulmonary symptoms in ankylosing spondylitis.

PMID- 11451864
TI  - Pharmacoeconomics of COPD and smoking cessation.

PMID- 11451865
TI  - Clavicle tapping and auscultation as an alternative to chest percussion when
      performing thoracocentesis.

PMID- 11451866
TI  - Performing thoracentesis.

PMID- 11451867
TI  - Alveolar hemorrhage associated with antiphospholipid syndrome.

PMID- 11451868
TI  - Lost in the labyrinth of end points.

PMID- 11451869
TI  - Lung cancer clarifications.

PMID- 11451879
TI  - Type 1/type 2 cytokine paradigm and the progression of pulmonary fibrosis.
AB  - The pathogenesis of end-stage, chronic lung disease is thought to be
      characterized by an initial inflammatory response followed by fibroproliferation
      and deposition of extracellular matrix. Many of these chronic lung disorders
      share a variety of common properties, including an unknown etiology, undefined
      mechanisms of initiation and maintenance, and progressive fibrosis.
      Unfortunately, efficacious therapeutic options are not readily available for the
      treatment of many chronic lung diseases, which may reflect the limited scientific
      and mechanistic understanding of these disorders. However, recent studies have
      shown that cytokine networks are likely operative in dictating the progression of
      these diseases, as these mediators can influence fibroblast activation,
      proliferation, and collagen deposition during the maintenance of chronic fibrotic
      lung disease. Accumulating data support the concept that the specific cytokine
      phenotype may provide a fundamental mechanism for the regulation or continuation
      of the fibrotic process. For example, interferon-gamma appears to suppresses
      fibroblast activities, such as proliferation and collagen production, while
      interleukin (IL)-4 and IL-13 can augment fibroblast growth and collagen
      production. Interestingly, these mediators are prototypic cytokines that
      functionally define either a type-1 or a type-2 immune response. Thus,
      experimental models of cell-mediated lung inflammation, which are characterized
      by either a type-1 or a type-2 response, will be useful in delineating the
      mechanisms that either maintain or resolve chronic lung inflammation and
      accompanying fibrosis.

PMID- 11451886
TI  - Alveolar epithelial cell chemokine expression induced by specific antiviral CD8+
      T-cell recognition plays a critical role in the perpetuation of experimental
      interstitial pneumonia.

PMID- 11451892
TI  - Extracellular matrix modulates expression of connexin messenger RNA and protein
      by alveolar epithelial cells.

PMID- 11451896
TI  - Fourteen-membered ring macrolides inhibit vascular cell adhesion molecule-1
      messenger RNA induction preventing neutrophil-induced lung injury and fibrosis in
      bleomycin-challenged mice.

PMID- 11451897
TI  - Transgenic mouse models to determine the role of epidermal growth factor receptor
      in epithelial cell proliferation, apoptosis, and asbestosis.

PMID- 11451898
TI  - Use of transgenic luciferase reporter mice to determine activation of
      transcription factors and gene expression by fibrogenic particles.

PMID- 11451901
TI  - Transgenic models for study of lung morphogenesis and repair: Parker B. Francis
      lecture.

PMID- 11451903
TI  - Epimorphin in bleomycin-induced pulmonary fibrosis in mice.

PMID- 11451905
TI  - Enhancement of fibrogenesis by the p53 tumor suppressor protein in asbestos
      exposed rodents.

PMID- 11451907
TI  - Evidence that neutrophil elastase-deficient mice are resistant to bleomycin
      induced fibrosis.

PMID- 11451908
TI  - Matrilysin in epithelial repair and defense.
AB  - Repair involves an orderly progression of events to reestablish the integrity of
      the injured tissue. During each stage in this process, secreted proteinases are
      needed to remodel extracellular matrix, facilitate cell migration, and process
      latent proteins, among other functions. In lung epithelium, several of these
      processes are mediated by matrilysin, a matrix metalloproteinase (MMP). Unlike
      most MMPs, matrilysin is produced by intact, noninjured airway and peribronchial
      epithelial cells. In other intact epithelial tissues, namely the small intestine,
      matrilysin functions in host defense by activating the latent form of defensins,
      a family of antimicrobial peptides. This metalloproteinase may serve a similar
      function in the lung. Furthermore, in models of airway injury, matrilysin
      expression is upregulated in migrating epithelial cells, and the activity of this
      proteinase is required for repair of airway wounds. These observations indicate
      that matrilysin serves key functions in both epithelial defense and repair.

PMID- 11451909
TI  - Mechanism of structural remodeling in pulmonary fibrosis.

PMID- 11451911
TI  - Is Smad3 a major player in signal transduction pathways leading to fibrogenesis?
AB  - Transforming growth factor (TGF)-beta plays a central role in fibrosis,
      contributing both to the influx and activation of inflammatory cells, as well as
      to activation of fibroblasts to elaborate extracellular matrix. In the past few
      years, new insight has been gained into signal transduction pathways downstream
      of the TGF-beta receptor serine-threonine kinases with the identification of a
      family of evolutionarily conserved Smad proteins. Two receptor-activated Smad
      proteins, Smad2 and Smad3, are phosphorylated by the activated TGF-beta type I
      receptor kinase, after which they partner with the common mediator, Smad4, and
      are translocated to the nucleus to where they participate in transcriptional
      complexes to control expression of target genes. We have shown in wound healing
      studies of mice null for Smad3, that loss of this key signaling intermediate
      interferes with the chemotaxis of inflammatory cells to TGF-beta as well as with
      their ability to autoinduce TGF-beta. Moreover, studies with mouse embryo
      fibroblasts null for Smad3 show that TGF-beta-dependent induction of c-Jun and c
      Fos, important in induction of collagen as well as in autoinduction of TGF-beta,
      is mediated by Smad3. Based on these observations, we hypothesize that loss of
      Smad3 will confer resistance to fibrosis and result in reduced inflammatory cell
      infiltrates, reduced autoinduction of TGF-beta, important to sustain the process,
      and reduced elaboration of collagen. Preliminary observations in a model of
      radiation-induced fibrosis confirm this hypothesis and suggest that inhibitors of
      Smad3 might have clinical application both to improve wound healing and to reduce
      fibrosis.

PMID- 11451912
TI  - Biological effects of transforming growth factor-beta(1) in idiopathic pulmonary
      fibrosis may be regulated by the activation of latent transforming growth factor
      beta(1) and the differential expression of transforming growth factor-beta
      receptors.

PMID- 11451913
TI  - Expression of transforming growth factor-beta induces fibroproliferative
      pulmonary disease in fibrosis-resistant mice.

PMID- 11451914
TI  - Integrin-mediated activation of transforming growth factor-beta(1) in pulmonary
      fibrosis.
AB  - The integrin alphavbeta6 is restricted to epithelial cells and is dramatically
      induced in response to injury and inflammation. Mice expressing a null mutation
      of this integrin develop exaggerated inflammation of the lungs and skin, but are
      dramatically protected from bleomycin-induced pulmonary fibrosis. This phenotype
      led to the identification of a unique role for this integrin in binding to and
      activating latent extracellular complexes of the anti-inflammatory, profibrotic
      cytokine, transforming growth factor-beta(1). This integrin-mediated activation
      is tightly spatially restricted and appears to require direct presentation of the
      activated cytokine to receptors on adjacent cells. The process also requires
      distinct regions of the beta6-subunit cytoplasmic domain and an intact actin
      cytoskeleton, suggesting the existence of additional cellular mechanisms to
      regulate this process. If this mechanism is found to be as important in humans as
      it is in mice, the integrin and as yet to be identified pathways for cellular
      regulation of this process could be exciting new targets for intervention in
      fibrotic diseases of the lung and other epithelial organs.

PMID- 11451915
TI  - Fibroblasts as sentinel cells: role of the CDcd40-CDcd40 ligand system in
      fibroblast activation and lung inflammation and fibrosis.

PMID- 11451917
TI  - Idiopathic pulmonary fibrosis can be an autosomal dominant trait in some
      families.

PMID- 11451924
TI  - Transforming growth factor-beta(1) modifies fibroblast growth factor-2 production
      in type II cells.
AB  - Transforming growth factor (TGF)-beta(1) is an inflammatory cytokine that plays
      multiple roles in pulmonary fibrosis. In vascular epithelium, it has been shown
      to regulate production and activity of fibroblast growth factor (FGF)-2, a potent
      type II cell mitogen in the lung. Such a relationship could have important
      consequences in prefibrotic change in the lung alveolus, where
      reepithelialization of alveolar surfaces is crucial. The goal of this study was
      to determine if FGF-2 production by alveolar type II cells is modulated by TGF
      beta(1) or FGF-1, another type II cell mitogen. Isolated rat type II cells were
      exposed to 0 to 40 ng/mL of TGF-beta(1) or 0 to 500 ng/mL of FGF-1 in serum-free
      medium for 1 to 3 days. Using a specific immunoassay, significant increases in
      FGF-2 protein in type II cell lysates were achieved after 1 day of exposure to
      100 ng/mL of FGF-1 and after 3 days of treatment with 8 ng/mL of TGF-beta(1).
      Similarly, transcripts for FGF-2 were dramatically increased with TGF-beta(1) or
      FGF-1, as were those for FGF receptor (FGFR)-1. These interactions were
      dramatically effected by the addition of heparin, a model sulfated extracellular
      matrix (ECM). Heparin as low as 0.01 mg/mL significantly downregulated expression
      of TGF-beta(1) and FGF-1-stimulated FGF-2 and FGFR-1. These results demonstrate
      important regulatory links between FGF-2, sulfated ECMs, and both TGF-beta(1) and
      FGF-1, which could contribute to the modulation of normal cell turnover,
      development, and repair processes attendant to fibrosis in the lung.

PMID- 11451928
TI  - Role of c-Jun N-terminal kinase in radiation-induced lung fibrosis.

PMID- 11451929
TI  - Differential expression, surface binding, and response to connective tissue
      growth factor in lung fibroblast subpopulations.

PMID- 11451930
TI  - T-cell activation in the lungs of patients with systemic sclerosis and its
      relation with pulmonary fibrosis.

PMID- 11451931
TI  - Circulating transforming growth factor-beta(1): a potential marker of disease
      activity during idiopathic pulmonary fibrosis.

PMID- 11451933
TI  - Influence of hyperglycemia to the severity of pulmonary fibrosis.

PMID- 11451934
TI  - Does reduced alpha(1)-antitrypsin activity explain the link between cigarette
      smoking and idiopathic pulmonary fibrosis?

PMID- 11451937
TI  - Increased detection of herpesvirus DNA in idiopathic pulmonary fibrosis.

PMID- 11451940
TI  - Mechanisms of pulmonary fibrosis: conference summary.

PMID- 11451943
TI  - Evidence for the vectorial nature of drug (substrate)-stimulated ATP hydrolysis
      by human P-glycoprotein.
AB  - P-glycoprotein (Pgp), the ATP-binding cassette multidrug transporter, exhibits a
      drug (substrate)-stimulatable ATPase activity, and vanadate (Vi) inhibits this
      activity by stably trapping the nucleoside diphosphate in the Pgp.ADP.Vi
      conformation. We recently demonstrated that Vi-induced 8-azido-[alpha-(32)P]ADP
      trapping into Pgp in the absence of substrate occurs both in the presence of 8
      azido-[alpha-(32)P]ATP (following 8-azido-ATP hydrolysis) or 8-azido-[alpha
      (32)P]ADP (without hydrolysis) and, the transition state intermediates generated
      under either condition are functionally indistinguishable. In this study, we
      compare the effect of substrates on Vi-induced 8-azido-[alpha-(32)P]ADP trapping
      into Pgp under both non-hydrolysis and hydrolysis conditions. We demonstrate that
      whereas substrates stimulate the Vi-induced trapping of 8-azido-[alpha-(32)P]ADP
      under hydrolysis conditions, they strongly inhibit Vi-induced trapping under non
      hydrolysis conditions. This inhibition is concentration-dependent, follows first
      order kinetics, and is effected by drastically decreasing the affinity of
      nucleoside diphosphate for Pgp during trapping. However, substrates do not affect
      the binding of nucleoside diphosphate in the absence of Vi, indicating that the
      substrate-induced conformation exerts its effect at a step distinct from
      nucleoside diphosphate-binding. Our results demonstrate that during the catalytic
      cycle of Pgp, although the transition state, Pgp x ADP x P(i) (Vi), can be
      generated both via the hydrolysis of ATP or by directly providing ADP to the
      system, in the presence of substrate the reaction is driven in the forward
      direction, i.e. hydrolysis of ATP. These data suggest that substrate-stimulated
      ATP hydrolysis by Pgp is a vectorial process.

PMID- 11451944
TI  - Characterization of a p75(NTR) apoptotic signaling pathway using a novel cellular
      model.
AB  - The p75 neurotrophin receptor (p75(NTR)) belongs to the tumor necrosis factor
      receptor/nerve growth factor receptor superfamily. In some cells derived from
      neuronal tissues it causes cell death through a poorly characterized pathway. We
      developed a neuronal system using conditionally immortalized striatal neurons, in
      which the expression of p75(NTR) is inducibly controlled by the ecdysone
      receptor. In these cells p75(NTR) induces apoptosis through its death domain in a
      nerve growth factor-independent manner. Caspases 9, 6, and 3 are activated by
      receptor expression indicating the activation of the common effector pathway of
      apoptosis. Cell death is blocked by a dominant negative form of caspase 9 and Bcl
      X(L) consistent with a pathway that involves mitochondria. Significantly, the
      viral flice inhibitory protein E8 protects from p75(NTR)-induced cell death
      indicating that death effector domains are involved. A p75(NTR) construct with a
      deleted death domain dominantly interferes with p75(NTR) signaling, implying that
      receptor multimerization is required. However, in contrast to the other receptors
      of the family, p75(NTR)-mediated apoptosis does not involve the adaptor proteins
      Fas-associated death domain protein or tumor necrosis factor-associated death
      domain protein, and the apical caspase 8 is not activated. We conclude that
      p75(NTR) signals apoptosis by similar mechanisms as other death receptors but
      uses different adaptors and apical caspases.

PMID- 11451945
TI  - Role of Cbfa1 in ameloblastin gene transcription.
AB  - Ameloblastin is a tooth-specific extracellular matrix protein that is thought to
      play a role in enamel crystal formation in the developing dentition. The murine
      ameloblastin promoter functions in a cell type-specific manner and contains cis
      acting elements that function both to enhance and to suppress transcription. The
      objective of this study was to determine whether the transcription factor Cbfa1,
      known to be essential for transcription of other mineralized tissue genes, is
      also required for ameloblastin transcription. Site-directed mutagenesis of the
      Cbfa1-binding site (-248 base pairs) termed osteoblast-specific element 2 (OSE2)
      decreased ameloblastin promoter activity by greater than 50% in ameloblast-like
      cells. No differences in promoter activity were observed in two other oral tissue
      derived cell lines transfected with similar constructs. Nuclear factor binding to
      the ameloblastin promoter was also shown to be cell type-specific and was altered
      by site-specific mutations in the OSE2 site. Cbfa1 was specifically shown to
      participate in the DNA-protein complexes between nuclear factors and the
      ameloblastin OSE2 site by supershift electrophoretic mobility shift assays. The
      findings that Cbfa1 interacts with functionally important regions of the
      ameloblastin promoter while promoter activity is diminished in constructs
      containing site-directed mutations in the Cbfa1 site indicate that Cbfa1
      possesses an important function in transcription of the ameloblastin gene.

PMID- 11451946
TI  - Induction of apoptosis by protein inhibitor of activated Stat1 through c-Jun NH2
      terminal kinase activation.
AB  - Members of the protein inhibitor of activated signal transducer and activator of
      transcription (STAT) family (PIAS family) of proteins act as negative regulators
      of STATs in cytokine signaling. We report here that PIAS proteins have
      proapoptotic activity. PIAS1 induced apoptosis in both human 293T cells and human
      osteosarcoma U2OS cells. PIAS1 is localized in the nucleus as distinct nuclear
      dots. Ectopic expression of PIAS1 in U2OS cells activated JNK1 (c-Jun NH(2)
      terminal kinase). A dominant-negative JNK1, capable of inhibiting PIAS1-induced
      JNK1 activation, blocked PIAS1-mediated apoptosis. Furthermore, a mutant PIAS1,
      lacking the first 9 amino acid residues, failed to repress Stat1-mediated gene
      activation although it retained its ability to activate JNK and to trigger
      apoptosis. Our results identify a novel function of PIAS1 in the induction of JNK
      dependent apoptosis, independent of the previously known inhibitory activity of
      PIAS1 in STAT-mediated gene activation.

PMID- 11451947
TI  - Expression of human cystatin A by keratinocytes is positively regulated via the
      Ras/MEKK1/MKK7/JNK signal transduction pathway but negatively regulated via the
      Ras/Raf-1/MEK1/ERK pathway.
AB  - Cystatin A, a cysteine proteinase inhibitor, is a cornified cell envelope
      constituent expressed in the upper epidermis. We previously reported that a
      potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate,
      increases human cystatin A expression by the activation of AP-1 proteins. Here,
      we delineate the signaling cascade responsible for this regulation. Co
      transfection of the cystatin A promoter into normal human keratinocytes together
      with a dominant active form of ras increased the promoter activity by 3-fold. In
      contrast, a dominant negative form of ras suppressed basal cystatin A promoter
      activity. Further analyses disclosed that transfection of dominant negative forms
      of raf-1, MEK1, ERK1, ERK2, or wild-type MEKK1 all increased cystatin A promoter
      activity in normal human keratinocytes, whereas wild-type raf-1, ERK1, ERK2, or
      dominant negative forms of MEKK1, MKK7, or JNK1 suppressed the promoter activity.
      The increased or decreased promoter activity reflected the expression of cystatin
      A on mRNA and protein levels. These effects were not observed when a cystatin A
      promoter with a T2 (-272 to -278) deletion was used. In contrast, transfection of
      dominant negative forms of MKK3, MKK4, or p38 did not affect cystatin A promoter
      activity. Immunohistochemical analyses revealed that phosphorylated active
      extracellular signal-regulated kinases and c-Jun N-terminal kinase were expressed
      in the nuclei of basal cells and cells in the suprabasal-granular cell layer,
      respectively. These results indicate that the expression of cystatin A is
      regulated via mitogen-activated protein kinase pathways positively by
      Ras/MEKK1/MKK7/JNK and negatively by Ras/Raf/MEK1/ERK.

PMID- 11451948
TI  - Crystal structure of a recombinant anti-estradiol Fab fragment in complex with
      17beta -estradiol.
AB  - The crystal structure of a Fab fragment of an anti-17beta-estradiol antibody 57-2
      was determined in the absence and presence of the steroid ligand, 17beta
      estradiol (E2), at 2.5 and 2.15-A resolutions, respectively. The antibody binds
      the steroid in a deep hydrophobic pocket formed at the interface between the
      variable domains. No major structural rearrangements take place upon ligand
      binding; however, a large part of the heavy chain variable domain near the
      binding pocket is unusually flexible and is partly stabilized when the steroid is
      bound. The nonpolar steroid skeleton of E2 is recognized by a number of
      hydrophobic interactions, whereas the two hydroxyl groups of E2 are hydrogen
      bonded to the protein. Especially, the 17-hydroxyl group of E2 is recognized by
      an intricate hydrogen bonding network in which the 17-hydroxyl itself forms a
      rare four-center hydrogen bond with three polar amino acids; this hydrogen
      bonding arrangement accounts for the low cross-reactivity of the antibody with
      other estrogens such as estrone. The CDRH3 loop plays a prominent role in ligand
      binding. All the complementarity-determining regions of the light chain make
      direct contacts with the steroid, even CDRL2, which is rarely directly involved
      in the binding of haptens.

PMID- 11451949
TI  - Lipoprotein lipase and leptin are accumulated in different secretory compartments
      in rat adipocytes.
AB  - Adipose cells produce and secrete several physiologically important proteins,
      such as lipoprotein lipase (LPL), leptin, adipsin, Acrp30, etc. However,
      secretory pathways in adipocytes have not been characterized, and vesicular
      carriers responsible for the accumulation and transport of secreted proteins have
      not been identified. We have compared the intracellular localization of two
      proteins secreted from adipose cells: leptin and LPL. Adipocytes accumulate large
      amounts of both proteins, suggesting that neither of them is targeted to the
      constitutive secretory pathway. By means of velocity centrifugation in sucrose
      gradients, equilibrium density centrifugation in iodixanol gradients, and
      immunofluorescence confocal microscopy, we determined that LPL and leptin were
      localized in different membrane structures. LPL was found mainly in the
      endoplasmic reticulum with a small pool being present in low density membrane
      vesicles that may represent a secretory compartment in adipose cells. Virtually
      all intracellular leptin was localized in these low density secretory vesicles.
      Insulin-sensitive Glut4 vesicles did not contain either LPL or leptin. Thus,
      secretion from adipose cells is controlled both at the exit from the endoplasmic
      reticulum as well as at the level of "downstream" secretory vesicles.

PMID- 11451950
TI  - Insertion of PsaK into the thylakoid membrane in a "Horseshoe" conformation
      occurs in the absence of signal recognition particle, nucleoside triphosphates,
      or functional albino3.
AB  - The photosystem I subunit PsaK spans the thylakoid membrane twice, with the N and
      C termini both located in the lumen. The insertion mechanism of a thylakoid
      membrane protein adopting this type of topology has not been studied before, and
      we have used in vitro assays to determine the requirements for PsaK insertion
      into thylakoids. PsaK inserts with high efficiency and we show that one
      transmembrane span (the C-terminal region) can insert independently of the other,
      indicating that a "hairpin"-type mechanism is not essential. Insertion of PsaK
      does not require stromal extract, indicating that signal recognition particle
      (SRP) is not involved. Removal of nucleoside triphosphates inhibits insertion
      only slightly, both in the presence and absence of stroma, suggesting a mild
      stimulatory effect of a factor in the translation system and again ruling out an
      involvement of SRP or its partner protein, FtsY. We, furthermore, find no
      evidence for the involvement of known membrane-bound translocation apparatus;
      proteolysis of thylakoids destroys the Sec and Tat translocons but does not block
      PsaK insertion, and antibodies against the Oxa1/YidC homolog, Alb3, block the SRP
      dependent insertion of Lhcb1 but again have no effect on PsaK insertion. Because
      YidC is required for the efficient insertion of every membrane protein tested in
      Escherichia coli (whether SRP-dependent or -independent), PsaK is the first
      protein identified as being independent of YidC/Alb3-type factors in either
      thylakoids or bacteria. The data raise the possibility of a wholly spontaneous
      insertion pathway.

PMID- 11451951
TI  - Human acid ceramidase: processing, glycosylation, and lysosomal targeting.
AB  - The biosynthesis of human acid ceramidase (hAC) starts with the expression of a
      single precursor polypeptide of approximately 53-55 kDa, which is subsequently
      processed to the mature, heterodimeric enzyme (40 + 13 kDa) in the
      endosomes/lysosomes. Secretion of hAC by either fibroblasts or acid ceramidase
      cDNA-transfected COS cells is extraordinarily low. Both lysosomal targeting and
      endocytosis critically depend on a functional mannose 6-phosphate receptor as
      judged by the following criteria: (i) hAC-precursor secretion by NH(4)Cl-treated
      fibroblasts and I-cell disease fibroblasts, (ii) inhibition of the formation of
      mature heterodimeric hAC in NH(4)Cl-treated fibroblasts or in I-cell disease
      fibroblasts, and (iii) blocked endocytosis of hAC precursor by mannose 6
      phosphate receptor-deficient fibroblasts or the addition of mannose 6-phosphate.
      The influence of the six individual potential N-glycosylation sites of human acid
      ceramidase on targeting, processing, and catalytic activity was determined by
      site-directed mutagenesis. Five glycosylation sites (sites 1-5 from the N
      terminus) are used. The elimination of sites 2, 4, and 6 has no influence on
      lysosomal processing or enzymatic activity of recombinant ceramidase. The removal
      of sites 1, 3, and 5 inhibits the formation of the heterodimeric enzyme form.
      None of the mutant ceramidases gave rise to an increased rate of secretion,
      suggesting that lysosomal targeting does not depend on one single carbohydrate
      chain.

PMID- 11451952
TI  - Hyaluronan enters keratinocytes by a novel endocytic route for catabolism.
AB  - Hyaluronan synthesized in the epidermis has an exceptionally short half-life,
      indicative of its catabolism by epidermal keratinocytes. An intracellular pool of
      endogenously synthesized hyaluronan, from 1 to 20 fg/cell, inversely related to
      cell density, was observed in cultured rat epidermal keratinocytes. More than 80%
      of the intracellular hyaluronan was small (<90 kDa). Approximately 25% of newly
      synthesized hyaluronan was endocytosed by the keratinocytes and had a half-life
      of 2-3 h. A biotinylated aggrecan G(1) domain/link protein probe demonstrated
      hyaluronan in small vesicles of approximately 100 nm diameter close to the plasma
      membrane, and in large vesicles and multivesicular bodies up to 1300 nm diameter
      around the nucleus. Hyaluronan did not co-localize with markers of lysosomes.
      However, inhibition of lysosomal acidification with NH(4)Cl or chloroquine, or
      treating the cells with the hyaluronidase inhibitor apigenin increased
      intracellular hyaluronan staining, suggesting that it resided in prelysosomal
      endosomes. Competitive displacement of hyaluronan from surface receptors using
      hyaluronan decasaccharides, resulted in a rapid disappearance of this endosomal
      hyaluronan (t(12) approximately 5 min), indicating its transitory nature. The
      ultrastructure of the hyaluronan-containing vesicles, co-localization with marker
      proteins for different vesicle types, and application of specific uptake
      inhibitors demonstrated that the formation of hyaluronan-containing vesicles did
      not involve clathrin-coated pits or caveolae. Treatment of rat epidermal
      keratinocytes with the OX50 monoclonal antibody against the hyaluronan receptor
      CD44 increased endosomal hyaluronan. However, no CD44-hyaluronan co-localization
      was observed intracellularly unless endosomal trafficking was retarded by
      monensin, or cultivation at 20 degrees C, suggesting CD44 recycling. Rat
      epidermal keratinocytes thus internalize a large proportion of their newly
      synthesized hyaluronan into non-clathrin-coated endosomes in a receptor mediated
      way, and rapidly transport it to slower degradation in the endosomal/lysosomal
      system.

PMID- 11451953
TI  - Expression of a micro-protein.
AB  - The smallest known open reading frame encodes the ribosomal protein L41, which in
      yeast is composed of only 24 amino acids, 17 of which are arginine or lysine.
      Because of the unique problems that might attend the translation of such a short
      open reading frame, we have investigated the properties and the translation of
      the mRNAs encoding L41. In Saccharomyces cerevisiae L41 is encoded by two linked
      genes, RPL41A and RPL41B. These genes give rise to mRNAs that have short 5'
      leaders of 18 and 22 nucleotides and rather long 3' leaders of 203 and 210
      nucleotides not including their poly(A) tails. The mRNAs are translated
      exclusively on monosomes, suggesting that ribosomes do not remain attached to the
      mRNA after termination of translation. Calculations based on the abundance of
      ribosomes and of L41 mRNA indicate that the entire translation event, from
      initiation through termination, must occur in approximately 2 s. Termination of
      translation after only 25 codons does not subject the mRNAs encoding L41 to
      nonsense-mediated decay. Surprisingly, despite the L41 ribosomal protein being
      conserved from the archaea through the mammalia, S. cerevisiae can grow
      relatively normally after deletion of both RPL41A and RPL41B.

PMID- 11451954
TI  - Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by
      SAE1/SAE2 and Ubc9.
AB  - Conjugation of the small ubiquitin-like modifier SUMO-1/SMT3C/Sentrin-1 to
      proteins in vitro is dependent on a heterodimeric E1 (SAE1/SAE2) and an E2
      (Ubc9). Although SUMO-2/SMT3A/Sentrin-3 and SUMO-3/SMT3B/Sentrin-2 share 50%
      sequence identity with SUMO-1, they are functionally distinct. Inspection of the
      SUMO-2 and SUMO-3 sequences indicates that they both contain the sequence psiKXE,
      which represents the consensus SUMO modification site. As a consequence SAE1/SAE2
      and Ubc9 catalyze the formation of polymeric chains of SUMO-2 and SUMO-3 on
      protein substrates in vitro, and SUMO-2 chains are detected in vivo. The ability
      to form polymeric chains is not shared by SUMO-1, and although all SUMO species
      use the same conjugation machinery, modification by SUMO-1 and SUMO-2/-3 may have
      distinct functional consequences.

PMID- 11451955
TI  - Stimulation of osteoprotegerin (OPG) gene expression by transforming growth
      factor-beta (TGF-beta). Mapping of the OPG promoter region that mediates TGF-beta
      effects.
AB  - Transforming growth factor-beta (TGF-beta) regulates osteoclastogenesis and
      osteoclast survival, in part through the induction of osteoprotegerin (OPG), a
      protein known to inhibit osteoclast formation and function. To explore the
      molecular basis of TGF-beta regulation of OPG expression, we evaluated the
      effects of TGF-beta on osteoclast formation, OPG protein secretion, mRNA
      expression, and gene transcription. The marked inhibitory effect of TGF-beta on
      osteoclast differentiation was confirmed in a co-culture model utilizing murine
      stromal/osteoblastic BALC cells and bone marrow hematopoietic precursors. This
      inhibition in osteoclast differentiation was preceded by a decrease in RANKL mRNA
      expression (5-fold) and a reciprocal increase in OPG mRNA (6.1-fold) and protein
      (7.1-fold) expression in BALC cells. At the promoter/transcriptional level, TGF
      beta treatment resulted in a 3-10-fold increase in reporter gene activity
      directed by a 5.9-kilobase fragment of the human OPG promoter in transfection
      assays performed in UMR106 cells. The effect of TGF-beta was mimicked by TGF
      beta2 and -beta3 but not by BMP-4, suggesting a TGF-beta signal-specific effect.
      Deletion analysis revealed that a 183-base pair region (-372 to -190) in the
      promoter was required for TGF-beta responsiveness, and this region was sufficient
      to confer TGF-beta inducibility to a heterologous (osteocalcin) minimal promoter.
      Substitution mutations that disrupted the Cbfa1- and/or Smad-binding elements
      present in the 183-base pair region resulted in a decrease in base-line
      expression and in the responsiveness to TGF-beta and Cbfa1. Collectively, these
      studies indicate the involvement and possible interaction of Cbfa1 and Smad
      proteins in mediating the effects of TGF-beta on OPG transcription.

PMID- 11451956
TI  - PsbT polypeptide is required for efficient repair of photodamaged photosystem II
      reaction center.
AB  - PsbT is a small chloroplast-encoded hydrophobic polypeptide associated with the
      photosystem II (PSII) core complex. A psbT-deficient mutant (Delta psbT) of the
      green alga Chlamydomonas reinhardtii grows photoautotrophically, whereas its
      growth is significantly impaired in strong light. To understand the
      photosensitivity of Delta psbT, we have studied the effect of strong illumination
      on PSII activity and proteins. It is shown that the level of PSII activity and
      proteins is reduced in the Delta psbT more significantly than in wild type under
      strong light. When recovery of the photodamaged PSII is inhibited by a
      chloroplast protein synthesis inhibitor, the light-induced inactivation and
      degradation of PSII occur similarly in wild-type and mutant cells. On the
      contrary, the recovery of PSII activity after partial photoinactivation is
      remarkably delayed in the Delta psbT cells, suggesting that PsbT is required for
      efficient recovery of the photodamaged PSII complex. These results therefore
      present the first evidence for involvement of this small PSII polypeptide in the
      recovery process. Partial disintegration of the purified PSII core complex and
      localization of PSII proteins in the resulting PSII subcore complexes have
      revealed that PsbT is associated with D1/D2 heterodimer. A possible role of PsbT
      in the recovery process is discussed.

PMID- 11451957
TI  - Palmitoylation of caveolin-1 at a single site (Cys-156) controls its coupling to
      the c-Src tyrosine kinase: targeting of dually acylated molecules (GPI-linked,
      transmembrane, or cytoplasmic) to caveolae effectively uncouples c-Src and
      caveolin-1 (TYR-14).
AB  - Caveolin-1 was initially identified as a phosphoprotein in Rous sarcoma virus
      transformed cells. Previous studies have shown that caveolin-1 is phosphorylated
      on tyrosine 14 by c-Src and that lipid modification of c-Src is required for this
      phosphorylation event to occur in vivo. Phosphocaveolin-1 (Tyr(P)-14) localizes
      within caveolae near focal adhesions and, through its interaction with Grb7,
      augments anchorage-independent growth and epidermal growth factor-stimulated cell
      migration. However, the cellular factors that govern the coupling of caveolin-1
      to the c-Src tyrosine kinase remain largely unknown. Here, we show that
      palmitoylation of caveolin-1 at a single site (Cys-156) is required for coupling
      caveolin-1 to the c-Src tyrosine kinase. Furthermore, upon evaluating a battery
      of nonreceptor and receptor tyrosine kinases, we demonstrate that the tyrosine
      phosphorylation of caveolin-1 by c-Src is a highly selective event. We show that
      Src-induced tyrosine phosphorylation of caveolin-1 can be inhibited or uncoupled
      by targeting dually acylated proteins (namely carcinoembryonic antigen (CEA),
      CD36, and the NH(2)-terminal domain of Galpha(i1)) to the exoplasmic,
      transmembrane, and cytoplasmic regions of the caveolae membrane, respectively.
      Conversely, when these proteins are not properly targeted or lipid-modified, the
      ability of c-Src to phosphorylate caveolin-1 remains unaffected. In addition,
      when purified caveolae preparations are preincubated with a myristoylated peptide
      derived from the extreme N terminus of c-Src, the tyrosine phosphorylation of
      caveolin-1 is abrogated; the same peptide lacking myristoylation has no
      inhibitory activity. However, an analogous myristoylated peptide derived from c
      Yes also has no inhibitory activity. Thus, the inhibitory effects of the
      myristoylated c-Src peptide are both myristoylation-dependent and sequence
      specific. Finally, we investigated whether phosphocaveolin-1 (Tyr(P)-14)
      interacts with the Src homology 2 and/or phosphotyrosine binding domains of Grb7,
      the only characterized downstream mediator of its function. Taken together, our
      data identify a series of novel lipid-lipid-based interactions as important
      regulatory factors for coupling caveolin-1 to the c-Src tyrosine kinase in vivo.

PMID- 11451958
TI  - Structural and biological characterization of chromofungin, the antifungal
      chromogranin A-(47-66)-derived peptide.
AB  - Vasostatin-I, the natural fragment of chromogranin A-(1-76), is a neuropeptide
      able to kill a large variety of fungi and yeast cells in the micromolar range. We
      have examined the antifungal properties of synthetic vasostatin-I-related
      peptides. The most active shortest peptide, named chromofungin, corresponds to
      the sequence Arg(47)-Leu(66). Extensive (1)H NMR analysis revealed that it adopts
      a helical structure. The biophysical mechanism implicated in the interaction of
      chromofungin with fungi and yeast cells was studied, showing the penetration of
      this peptide with different lipid monolayers. In order to examine thoroughly the
      antifungal activity of chromofungin, confocal laser microscopy was used to
      demonstrate the ability of the rhodamine-labeled peptide to interact with the
      fungal cell wall, to cross the plasma membrane, and to accumulate in Aspergillus
      fumigatus, Alternaria brassicola, and Candida albicans. Our present data reveal
      that chromofungin inhibits calcineurin activity, extending a previous observation
      that the N-terminal region of chromogranin A interacts with calmodulin in the
      presence of calcium. Therefore, the destabilization of fungal wall and plasma
      membrane, together with the possible intracellular inhibition of calmodulin
      dependent enzymes, is likely to represent the mechanism by which vasostatin-I and
      chromofungin exert antifungal activity.

PMID- 11451959
TI  - Glutamate 170 of human l-3-hydroxyacyl-CoA dehydrogenase is required for proper
      orientation of the catalytic histidine and structural integrity of the enzyme.
AB  - l-3-Hydroxyacyl-CoA dehydrogenase (HAD), the penultimate enzyme in the beta
      oxidation spiral, reversibly catalyzes the conversion of l-3-hydroxyacyl-CoA to
      the corresponding 3-ketoacyl-CoA. Similar to other dehydrogenases, HAD contains a
      general acid/base, His(158), which is within hydrogen bond distance of a
      carboxylate, Glu(170). To investigate its function in this catalytic dyad,
      Glu(170) was replaced with glutamine (E170Q), and the mutant enzyme was
      characterized. Whereas substrate and cofactor binding were unaffected by the
      mutation, E170Q exhibited diminished catalytic activity. Protonation of the
      catalytic histidine did not restore wild-type activity, indicating that
      modulation of the pK(a) of His(158) is not the sole function of Glu(170). The pH
      profile of charge transfer complex formation, an independent indicator of active
      site integrity, was unaltered by the amino acid substitution, but the intensity
      of the charge transfer band was diminished. This observation, coupled with
      significantly reduced enzymatic stability of the E170Q mutant, implicates
      Glu(170) in maintenance of active site architecture. Examination of the crystal
      structure of E170Q in complex with NAD(+) and acetoacetyl-CoA (R = 21.9%, R(free)
      = 27.6%, 2.2 A) reveals that Gln(170) no longer hydrogen bonds to the side chain
      of His(158). Instead, the imidazole ring is nearly perpendicular to its placement
      in the comparable native complex and no longer positioned for efficient
      catalysis.

PMID- 11451960
TI  - Bi-site catalysis in F1-ATPase: does it exist?
AB  - The mechanism of action of F(1)F(0)-ATP synthase is controversial. Some favor a
      tri-site mechanism, where substrate must fill all three catalytic sites for
      activity, others a bi-site mechanism, where one of the three sites is always
      unoccupied. New approaches were applied to examine this question. First, ITP was
      used as hydrolysis substrate; lower binding affinities of ITP versus ATP enable
      more accurate assessment of sites occupancy. Second, distributions of all eight
      possible enzyme species (with zero, one, two or three sites filled) as fraction
      of total enzyme population at each ITP concentration were calculated, and
      compared with measured ITPase activity. Confirming data were obtained with ATP as
      substrate. Third, we performed a theoretical analysis of possible bi-site
      mechanisms. The results argue convincingly that bi-site hydrolysis activity is
      negligible, and may not even exist. Effectively, tri-site hydrolysis is the only
      mechanism. We argue that only tri-site hydrolysis drives subunit rotation.
      Theoretical analyses of possible bi-site mechanisms reveal serious flaws, not
      previously recognized. One is that, in bi-site catalysis, the predicted direction
      of subunit rotation is the same for both ATP synthesis and hydrolysis; a second
      is that infrequently occurring enzyme species are required.

PMID- 11451961
TI  - Negative regulation of neuroblastoma cell growth by carbohydrate-dependent
      surface binding of galectin-1 and functional divergence from galectin-3.
AB  - The cell density-dependent growth inhibition of human SK-N-MC neuroblastoma cells
      is initiated by increased ganglioside sialidase activity leading to elevated cell
      surface presentation of ganglioside GM1, a ligand of galectin-1. We herein show
      that the extent of the cell surface expression of the galectin coincides with
      marked increases of the sialidase activity. Reverse transcriptase-polymerase
      chain reaction analysis excludes a regulation at the transcriptional level.
      Exposure of cells to purified galectin-1 reveals its carbohydrate-dependent
      activity to reduce cell proliferation. Assays to detect DNA fragmentation
      biochemically and cytometrically and to block caspases render it unlikely that
      galectin-1 acts as a classical proapoptotic factor on these cells. Because the
      chimeric galectin-3 shares binding sites and binding parameters with galectin-1
      for these cells, we tested whether this galectin will elicit the same response as
      the homodimeric cross-linking galectin-1. Evidently, galectin-3 fails to affect
      cell growth by itself but interferes with galectin-1 upon coincubation. Its
      proteolytically truncated variant, the C-terminal lectin domain with impaired
      capacity to form aggregates when surface bound, has only weak binding properties.
      Thus, the way in which the galectin-1 interacts topologically with an apparently
      common set of ligands relative to galectin-3 is crucial for eliciting post
      binding events. We conclude that galectin-1 is a probable effector in the
      sialidase-dependent growth control in this system. Moreover, the experiments with
      galectin-3 reveal functional divergence, most probably based on different
      topologies of presentation of homologous carbohydrate-binding sites.

PMID- 11451962
TI  - Co-localization of leukotriene a4 hydrolase with 5-lipoxygenase in nuclei of
      alveolar macrophages and rat basophilic leukemia cells but not neutrophils.
AB  - The synthesis of leukotriene B(4) from arachidonic acid requires the sequential
      action of two enzymes: 5-lipoxygenase and leukotriene A(4) hydrolase. 5
      Lipoxygenase is known to be present in the cytoplasm of some leukocytes and able
      to accumulate in the nucleoplasm of others. In this study, we asked if
      leukotriene A(4) hydrolase co-localizes with 5-lipoxygenase in different types of
      leukocytes. Examination of rat basophilic leukemia cells by both
      immunocytochemistry and immunofluorescence revealed that leukotriene A(4)
      hydrolase, like 5-lipoxygenase, was most abundant in the nucleus, with only minor
      occurrences in the cytoplasm. The finding of abundant leukotriene A(4) hydrolase
      in the soluble nuclear fraction was substantiated by two different cell
      fractionation techniques. Leukotriene A(4) hydrolase was also found to accumulate
      together with 5-lipoxygenase in the nucleus of alveolar macrophages. This result
      was obtained using both in situ and ex vivo techniques. In contrast to these
      results, peripheral blood neutrophils contained both leukotriene A(4) hydrolase
      and 5-lipoxygenase exclusively in the cytoplasm. After adherence of neutrophils,
      5-lipoxygenase was rapidly imported into the nucleus, whereas leukotriene A(4)
      hydrolase remained cytosolic. Similarly, 5-lipoxygenase was localized in the
      nucleus of neutrophils recruited into inflamed appendix tissue, whereas
      leukotriene A(4) hydrolase remained cytosolic. These results demonstrate for the
      first time that leukotriene A(4) hydrolase can be accumulated in the nucleus,
      where it co-localizes with 5-lipoxygenase. As with 5-lipoxygenase, the
      subcellular distribution of leukotriene A(4) hydrolase is cell-specific and
      dynamic, but differences in the mechanisms regulating nuclear import must exist.
      The degree to which these two enzymes are co-localized may influence their
      metabolic coupling in the conversion of arachidonic acid to leukotriene B(4).

PMID- 11451963
TI  - Requirement of multiple protein domains and residues for gating K(ATP) channels
      by intracellular pH.
AB  - ATP-sensitive K(+) channels (K(ATP)) are regulated by pH in addition to ATP, ADP,
      and phospholipids. In the study we found evidence for the molecular basis of
      gating the cloned K(ATP) by intracellular protons. Systematic constructions of
      chimerical Kir6.2-Kir1.1 channels indicated that full pH sensitivity required the
      N terminus, C terminus, and M2 region. Three amino acid residues were identified
      in these protein domains, which are Thr-71 in the N terminus, Cys-166 in the M2
      region, and His-175 in the C terminus. Mutation of any of them to their
      counterpart residues in Kir1.1 was sufficient to completely eliminate the pH
      sensitivity. Creation of these residues rendered the mutant channels clear pH
      dependent activation. Thus, critical players in gating K(ATP) by protons are
      demonstrated. The pH sensitivity enables the K(ATP) to regulate cell excitability
      in a number of physiological and pathophysiological conditions when pH is low but
      ATP concentration is normal.

PMID- 11451964
TI  - Epoxygenase pathways of arachidonic acid metabolism.

PMID- 11451965
TI  - Retrieved human allografts : a clinicopathological study.
AB  - BACKGROUND: We studied seventy-three massive preserved human allografts,
      retrieved from two to 156 months after implantation, to provide insight into the
      mechanisms of their repair. METHODS: The specimens were studied with radiographic
      and histological techniques that permitted time-related quantitative analysis of
      the reparative mechanisms of union, cortical repair, soft-tissue attachment,
      fracture, and characteristics of the allograft-cement interface and the articular
      cartilage. RESULTS: Union at cortical-cortical junctions occurred slowly
      (approximately twelve months) by host-derived external callus that bridged the
      junction and filled the gap between abutting cortices. The bone in the gap did
      not undergo stress-oriented remodeling even after many years, and, when the union
      was intentionally disrupted, failure occurred at the cement line that marked the
      allograft-host junction. Repair of the necrotic graft matrix was both external
      and internal. External repair consisted of the apposition of a thin seam of host
      bone on the outer surface of the graft, coating about 40% of the surface at one
      year and 80% at two years. Internal repair was confined to the ends and the
      periphery of the cortices and penetrated so slowly that only 15% to 20% of the
      graft was repaired by five years, after which deeper repair seldom occurred.
      Graft fractures in specimens retrieved soon after fracture showed only necrotic
      bone adjacent to the fracture site, whereas those retrieved after fracture
      healing showed a marked increase in internal repair of the bone about the
      fracture site. When bone cement had been used to fix a prosthesis, there was no
      evidence of bone resorption or loosening of the device. The osteoarticular
      specimens showed no survival of chondrocytes in the articular cartilage. However,
      the architecture of the acellular cartilage was well preserved after two to three
      years and occasionally after as many as five years. Late degenerative changes in
      the articular cartilage coincided with subchondral revascularization and
      fragmentation, and the articulating surfaces became covered by a pannus of
      fibrovascular reparative tissue. Degenerative changes in articular cartilage
      occurred earlier and were more advanced in specimens retrieved from patients with
      an unstable joint than in those retrieved from patients with a stable joint.
      CONCLUSIONS: Repair of massive human allografts is an indolent process that
      follows a fairly predictable course during the first few years and is influenced
      by other biological activities, such as fracture repair, supplementary
      autografting, and tumor recurrence.

PMID- 11451966
TI  - The Internet as a communication tool for academic orthopaedic surgery departments
      in the United States.
AB  - BACKGROUND: The Internet's appeal as an affordable, accessible medium for
      information transfer makes it a potentially useful tool for practicing
      physicians. In the past several years, Internet-based health-care companies have
      proliferated, and many medical centers have established individual web sites. The
      purpose of the present study was to evaluate academic orthopaedic surgery
      departments in the United States with respect to Internet visibility and content.
      METHODS: We reviewed existing web sites for the 154 departments or divisions of
      orthopaedic surgery currently accredited for resident education by the
      Accreditation Council for Graduate Medical Education. The study sample consisted
      of the 113 departments that had a web page listed in the FREIDA (Fellowship and
      Residency Electronic Interactive Database) database. Each web site was assessed
      with regard to its informational value in the categories of clinical services,
      resident education, and physician recruitment. In addition, three commonly
      employed browsing engines were used to search for individual web sites and to
      determine their ease of accessibility. RESULTS: In the category of clinical
      services, sixty-five (57.5%) of the 113 sites provided faculty listings and forty
      nine (43.4%) provided office telephone numbers and locations. Only thirteen sites
      provided information on common orthopaedic conditions, and five had links to
      other patient-education sites. In the category of resident education, twenty-four
      sites (21.2%) had online academic schedules, but only two provided access to
      complete conferences or teaching files. In the category of physician recruitment,
      ninety-one provided a description of their residency program and fifty-four had
      information on the application process, but only twenty-six web pages offered
      detailed departmental statistics. In terms of accessibility, fifty-three programs
      (46.9%) were identified by one of three popular search engines, seventeen (15%)
      were identified by more than one search engine, and two (1.8%) were identified by
      all three. CONCLUSIONS: Academic orthopaedic surgery departments in the United
      States underutilize the Internet as a source of clinical and educational
      services. In addition, existing orthopaedic web sites are difficult to access
      with use of popular search engines. Thus, academic orthopaedic surgery
      departments in the United States are missing a valuable opportunity to promote
      awareness of their institutions and to become educational resources for the
      community.

PMID- 11451967
TI  - Total hip arthroplasty for the treatment of ankylosed hips : a five to twenty-one
      year follow-up study.
AB  - BACKGROUND: The purpose of the present retrospective study was to report the long
      term results of total hip arthroplasty following a hip fusion. Special attention
      was paid to the resulting function of both the involved joint and the neighboring
      joints, as pain in the lower back or knee was the usual indication for
      conversion. The factors that were likely to influence the functional outcome were
      analyzed. METHODS: Forty-five consecutive total hip arthroplasties were performed
      in forty-five patients from 1969 through 1993. The mean age of the patients at
      the time of the operation was 55.8 years (range, twenty-eight to eighty years).
      Ankylosis of the hip had been spontaneous in twenty patients and postoperative in
      twenty-five patients. The mean duration of the ankylosis had been thirty-six
      years (range, three to sixty-five years). The mean duration of follow-up was 8.5
      years (range, five to twenty-one years). No patient was lost to follow-up.
      RESULTS: The mean hip score, according to the scale of Merle d'Aubigne, was 16.5
      1.5 points at the latest follow-up evaluation. Hip function was considered to be
      satisfactory for forty-one (91%) of the forty-five patients. The definitive score
      for walking ability was not achieved by the one-year evaluation; it improved
      notably for two to three years and then it remained stable. At the time of the
      latest follow-up, the mean arc of flexion was 88 degrees (range, 30 degrees to
      130 degrees ). Forty-three (96%) of the forty-five patients had no pain in the
      involved joint. The only factor that was predictive of the final functional
      result with regard to walking ability was the intraoperative status of the
      gluteal muscles. Most patients had effective pain relief in the neighboring
      joints. The cumulative survival rate at eight years, with revision as the end
      point, was 96.7% (95% confidence interval, 90.2% to 100%). CONCLUSIONS: The long
      term effectiveness of total hip arthroplasty for the treatment of an ankylosed
      hip was clearly demonstrated in both the involved and the neighboring joints in
      the present study. However, the preoperative and intraoperative status of the
      gluteal muscles should be carefully evaluated when this procedure is being
      considered, as this was the only factor that was predictive of the final walking
      ability.

PMID- 11451968
TI  - Use of the Swanson silicone trapezium implant for treatment of primary
      osteoarthritis : long-term results.
AB  - BACKGROUND: Instability of the prosthesis and silicone-induced synovitis have led
      most surgeons to abandon use of the Swanson trapezium implant for the treatment
      of primary osteoarthritis. However, the literature contains little information on
      the results of long-term follow-up. The present study was conducted to establish
      the long-term results and to highlight the problems associated with the implant.
      METHODS: Thirty-five patients (forty-five implants) of our initial forty-five
      patients (fifty-seven implants) were available for clinical review. The mean
      duration of follow-up was 13.8 years. The objective result was assessed with a 40
      point clinical scoring system. The subjective result was measured with a visual
      analog scale. A clinical score of 30 to 40 points and a subjective score of 8, 9,
      or 10 points were considered a good-to-excellent result. Radiographs were
      evaluated to determine the position and deformation of the prosthesis and to
      check for osteolytic changes of the bone, indicating silicone-induced synovitis.
      RESULTS: The overall clinical and subjective results were good for twenty-seven
      thumbs (60%). Eighteen thumbs (40%) had a dislocation, and nine of them had a
      revision. Three more revisions were carried out because of silicone-induced
      synovitis, persistent pain after reflex sympathetic dystrophy, and deep infection
      in one thumb each. Revision surgery consisted of resection of the implant, with
      or without tendon interposition, or implantation of a new prosthesis. Of the
      thirty-two prostheses (thirty that had not been revised and two that had been
      revised) for which follow-up radiographs were available, six (19%) showed wear
      and deformation and five (16%) also were associated with osteolytic changes.
      CONCLUSIONS: The main problem associated with the prosthesis was dislocation.
      Surgical measures to improve stability did not prevent this complication. The
      results after revision because of dislocation were no better than those
      associated with unrevised dislocated implants. In addition to dislocation,
      radiographic signs of silicone-induced synovitis were frequently noted, although
      they did not necessarily lead to a poor result. We concluded that the results
      after long-term follow-up of the Swanson silicone trapezium implant for the
      treatment of primary osteoarthritis were poor and that our decision to stop using
      this implant in 1991 was correct.

PMID- 11451969
TI  - Patients' expectations of knee surgery.
AB  - BACKGROUND: Patients' expectations of medical care are linked to their requests
      for treatment and to their assessments of outcome and satisfaction. Our goals
      were to measure patients" preoperative expectations of knee surgery and to
      develop and test patient-derived knee expectations surveys. METHODS: An initial
      sample of 377 patients (mean age, 54.6 18.2 years; 52% women) was enrolled in the
      survey-development phase. One hundred and sixty-one (43%) of these patients
      subsequently underwent total knee arthroplasty; seventy-five (20%), cruciate
      ligament repair; eighty-five (23%), meniscal surgery; and fifty-six (15%),
      surgery for another knee condition. Preoperatively, these patients were asked
      open-ended questions about their expectations of knee surgery. Their responses
      were grouped with use of qualitative research techniques to generate categories
      of expectations. Categories were transformed into specific questions and were
      formatted into two draft surveys, one for patients undergoing total knee
      arthroplasty and one for patients undergoing other surgical procedures on the
      knee. A second sample of 163 patients (mean age, 55.1 17.5 years; 49% women) was
      enrolled in the survey-testing phase, and they completed the draft surveys on two
      separate occasions to establish test-retest reliability. Items were selected for
      the final surveys if they were cited by 5% of the patients, if they represented
      important functional changes resulting from surgery, or if they represented
      potentially unrealistic expectations. All selected items fulfilled reliability
      criteria, defined as a kappa (or weighted kappa) value of 0.4, or were deemed to
      be clinically relevant by a panel of orthopaedic surgeons. RESULTS: From the
      survey-development phase, a total of fifty-two categories of expectations were
      discerned; they included both anticipated items such as pain relief and
      improvement in walking ability and unanticipated items such as improving
      psychological well-being. Expectations varied by diagnosis and patient
      characteristics, including functional status. Two final surveys were generated:
      the seventeen-item Hospital for Special Surgery Knee Replacement Expectations
      Survey and the twenty-item Hospital for Special Surgery Knee Surgery Expectations
      Survey. Each required less than five minutes to complete. CONCLUSIONS: Patients
      have multiple expectations of knee surgery in the areas of symptom relief and
      improvement of physical and psychosocial function, and these expectations vary
      according to the diagnosis. We developed two valid and reliable surveys that can
      be used preoperatively to direct patient education and shared decision-making and
      to provide a framework for setting reasonable goals. Reexamining patients'
      responses postoperatively could provide a way to assess fulfillment of
      expectations, which is a crucial patient-derived measure of outcome and
      satisfaction.

PMID- 11451970
TI  - Strut-autografting with and without osteogenic protein-1 : a preliminary study of
      a canine femoral head defect model.
AB  - BACKGROUND: Osteonecrosis of the femoral head frequently leads to collapse of the
      articular cartilage and to disabling osteoarthritis, which ultimately may
      necessitate joint arthroplasty. One treatment method that has had moderate
      success is the so-called trapdoor approach, which involves excavation of diseased
      (necrotic) bone followed by bone-grafting. Augmentation of this procedure with
      various growth and differentiation factors may improve the outcome. We developed
      a canine model that mimics the clinical situation with trapdoor bone-grafting.
      The objective of this study was to evaluate the effect of the addition of
      osteogenic protein-1 on healing following the trapdoor procedure with strut
      autografting. METHODS: Thirty-four skeletally mature dogs were used in the
      experiment. After capsulotomy, a trapdoor was created in the anterolateral
      surface of the femoral head and a 2-cm-diameter subchondral area of bone was
      removed. In the phase-I experiments, seven dogs had no treatment of the defect
      (Group I) and nine dogs were treated with strut-grafting (Group II). In phase II,
      the procedure was modified by collapsing the trapdoor into the created defect
      intraoperatively in eighteen dogs, which were divided into three equal groups:
      six untreated defects were left collapsed (Group III), six were treated with bone
      graft (Group IV), and six were treated with bone graft augmented with osteogenic
      protein-1 (Group V). RESULTS: Three of the seven femoral heads in Group I
      (untreated defect) and one of the nine heads in Group II (grafting without
      collapsing of the trapdoor) had evidence of cartilage collapse. Inspection of
      sagittal slices and radiographs revealed an unfilled residual defect in all Group
      I heads, whereas all Group-II heads were well healed. The mean normalized
      stiffness value was significantly larger in Group II than it was in Group I. On
      visual inspection, depression was noted in all of the femoral heads in Group III
      (untreated defect; trapdoor left collapsed). In both Group IV and Group V
      (grafting without and with osteogenic protein-1), the trapdoor cartilage appeared
      to be essentially normal. Groups IV and V had more radiographic healing than did
      Group III. The defects in Group V (grafting with osteogenic protein-1) healed
      faster radiographically than did those in Group IV (grafting without osteogenic
      protein-1). CONCLUSIONS: Moderate-to-excellent healing was seen both
      radiographically and biomechanically by four months in the groups treated with
      grafting, with and without osteogenic protein-1, whereas untreated defects did
      not heal. CLINICAL RELEVANCE: Symptomatic osteonecrosis of the femoral head is a
      clinical challenge. The animal model in the current study is a useful tool for
      the evaluation of methods to treat osteonecrosis of the femoral head. Studies
      investigating additional time-periods between implantation of osteogenic protein
      1 and assessment of results as well as different doses of osteogenic protein-1
      are warranted.

PMID- 11451971
TI  - Femoral revision with the Wagner SL revision stem : evaluation of one hundred and
      twenty-nine revisions followed for a mean of 4.8 years.
AB  - BACKGROUND: It is difficult to achieve a successful revision total hip
      replacement when a patient has severe proximal femoral bone loss. The Wagner SL
      revision stem has some theoretical advantages, but the durability of this
      prosthesis is not known. METHODS: We reviewed the results of 129 revisions of the
      femoral component with a Wagner SL revision stem in 123 patients. The indication
      for revision was aseptic loosening in ninety-seven hips, periprosthetic fracture
      in thirteen (one of which also had an infection), and septic loosening in
      sixteen. In the three remaining hips, a Wagner revision stem was inserted during
      a second-stage reimplantation after the performance of a Girdlestone resection
      arthroplasty to treat chronic deep infection. The prerevision defects were
      classified with the system described by Pak et al. as well as with our system. A
      functional evaluation of the patients and a survival analysis of the revision
      stems were performed. RESULTS: The mean duration of follow-up was 4.8 years
      (range, two months to 11.1 years). Six revision stems required repeat revision.
      With removal of the stem for any cause or the worst case (removal of the stem for
      any cause and/or lost to follow-up) as the end point, cumulative survival at 11.1
      years was 93.9% and 92.8%, respectively. The mean Merle d'Aubigne score improved
      from 7.7 points preoperatively to 14.8 points at the latest follow-up
      examination. The most recent radiographs showed good or excellent restoration of
      the proximal part of the femur in 113 hips (88%). CONCLUSIONS: Because of the
      encouraging results of implantation of this femoral component with distal
      fixation, we will continue to use it in the majority of femoral revisions.
      However, the need for regular follow-up remains, since the rate of complications
      such as osteolysis of the femur, aseptic loosening, periprosthetic fracture, and
      late infection may increase in the future.

PMID- 11451972
TI  - Effect of bone morphogenetic protein-2-expressing muscle-derived cells on healing
      of critical-sized bone defects in mice.
AB  - BACKGROUND: Cells that express bone morphogenetic protein-2 (BMP-2) can now be
      prepared by transduction with adenovirus containing BMP-2 cDNA. Skeletal muscle
      tissue contains cells that differentiate into osteoblasts on stimulation with BMP
      2. The objectives of this study were to prepare BMP-2-expressing muscle-derived
      cells by transduction of these cells with an adenovirus containing BMP-2 cDNA and
      to determine whether the BMP-2-expressing muscle-derived cells would elicit the
      healing of critical-sized bone defects in mice. METHODS: Primary cultures of
      muscle-derived cells from a normal male mouse were transduced with adenovirus
      encoding the recombinant human BMP-2 gene (adBMP-2). These cells (5 yen 10(5))
      were implanted into a 5-mm-diameter critical-sized skull defect in female SCID
      (severe combined immunodeficiency strain) mice with use of a collagen sponge as a
      scaffold. Healing in the treatment and control groups was examined grossly and
      histologically at two and four weeks. Implanted cells were identified in vivo
      with use of the Y-chromosome-specific fluorescent in situ hybridization (FISH)
      technique, and their differentiation into osteogenic cells was demonstrated by
      osteocalcin immunohistochemistry. RESULTS: Skull defects treated with muscle
      cells that had been genetically engineered to express BMP-2 had >85% closure
      within two weeks and 95% to 100% closure within four weeks. Control groups in
      which the defect was not treated (group 1), treated with collagen only (group 2),
      or treated with collagen and muscle cells without adBMP-2 (group 3) showed at
      most 30% to 40% closure of the defect by four weeks, and the majority of the
      skull defects in those groups showed no healing. Analysis of injected cells in
      group 4, with the Y-chromosome-specific FISH technique showed that the majority
      of the transplanted cells were located on the surfaces of the newly formed bone,
      but a small fraction (approximately 5%) was identified within the osteocyte
      lacunae of the new bone. Implanted cells found in the new bone stained
      immunohistochemically for osteocalcin, indicating that they had differentiated in
      vivo into osteogenic cells. CONCLUSIONS: This study demonstrates that cells
      derived from muscle tissue that have been genetically engineered to express BMP-2
      elicit the healing of critical-sized skull defects in mice. The cells derived
      from muscle tissue appear to enhance bone-healing by differentiating into
      osteoblasts in vivo. CLINICAL RELEVANCE: Ex vivo gene therapy with muscle-derived
      cells that have been genetically engineered to express BMP-2 may be used to treat
      nonhealing bone defects. In addition, muscle-derived cells appear to include stem
      cells, which are easily obtained with muscle biopsy and could be used in gene
      therapy to deliver BMP-2.

PMID- 11451973
TI  - Reliability and intraoperative validity of preoperative assessment of
      standardized plain radiographs in predicting bone loss at revision hip surgery.
AB  - BACKGROUND: The most challenging aspect of revision hip surgery is the management
      of bone loss. A reliable and valid measure of bone loss is important since it
      will aid in future studies of hip revisions and in preoperative planning. We
      developed a measure of femoral and acetabular bone loss associated with failed
      total hip arthroplasty. The purpose of the present study was to measure the
      reliability and the intraoperative validity of this measure and to determine how
      it may be useful in preoperative planning. METHODS: From July 1997 to December
      1998, forty-five consecutive patients with a failed hip prosthesis in need of
      revision surgery were prospectively followed. Three general orthopaedic surgeons
      were taught the radiographic classification system, and two of them classified
      standardized preoperative anteroposterior and lateral hip radiographs with use of
      the system. Interobserver testing was carried out in a blinded fashion. These
      results were then compared with the intraoperative findings of the third surgeon,
      who was blinded to the preoperative ratings. Kappa statistics (unweighted and
      weighted) were used to assess correlation. Interobserver reliability was assessed
      by examining the agreement between the two preoperative raters. Prognostic
      validity was assessed by examining the agreement between the assessment by either
      Rater 1 or Rater 2 and the intraoperative assessment (reference standard).
      RESULTS: With regard to the assessments of both the femur and the acetabulum,
      there was significant agreement (p < 0.0001) between the preoperative raters
      (reliability), with weighted kappa values of >0.75. There was also significant
      agreement (p < 0.0001) between each rater's assessment and the intraoperative
      assessment (validity) of both the femur and the acetabulum, with weighted kappa
      values of >0.75. CONCLUSIONS: With use of the newly developed classification
      system, preoperative radiographs are reliable and valid for assessment of the
      severity of bone loss that will be found intraoperatively.

PMID- 11451974
TI  - Mechanical prophylaxis against deep-vein thrombosis after pelvic and acetabular
      fractures.
AB  - BACKGROUND: Deep-vein thrombosis is a common complication following pelvic and
      acetabular fractures. The hypothesis of this study was that pulsatile mechanical
      compression is superior to standard sequential mechanical compression for
      decreasing the prevalence of deep-vein thrombosis in patients with pelvic or
      acetabular fracture. METHODS: A prospective, randomized, blinded study of two
      methods of mechanical prophylaxis against deep-vein thrombosis was conducted. One
      hundred and seven patients were randomized into either Group A (fifty-four
      patients), in which a thigh-calf low-pressure sequential-compression device was
      used, or Group B (fifty-three patients), in which a calf-foot high-pressure
      pulsatile-compression pump was used. All patients underwent duplex
      ultrasonography and magnetic resonance venography. The two groups were comparable
      with regard to demographics, fracture type, fracture treatment, time from the
      injury to the prophylaxis, and patient compliance. RESULTS: Deep-vein thrombosis
      developed in ten patients (19%) in Group A, with seven (13%) having a large or
      occlusive clot and one (2%) having a documented pulmonary embolism. Deep-vein
      thrombosis developed in five patients (9%) in Group B, with two (4%) having a
      large or occlusive clot and none having a documented pulmonary embolism. Nine of
      the nineteen detected thromboses were in the deep pelvic veins. The difference in
      the prevalence of large or occlusive clots between the two groups demonstrated a
      trend but, with the numbers available, was not significant (p = 0.16). Increased
      patient age and the time elapsed from the injury to the surgery were found to be
      associated with higher rates of thrombosis. CONCLUSIONS: Pulsatile compression
      was associated with fewer deep-vein thromboses than was standard compression,
      with the difference representing a trend but not reaching significance with the
      number of patients studied.

PMID- 11451975
TI  - Prospective longitudinal analysis of postoperative shoulder function : a ten-year
      follow-up study of full-thickness rotator cuff tears.
AB  - BACKGROUND: Rotator cuff repair is associated with good short or mid-term
      results, but to date there have been no long-term functional outcome studies
      demonstrating durability of results over time. In most long-term studies, the
      results have been compared with those of historical controls or with those of
      other, short-term follow-up studies. The purpose of the present prospective study
      was to evaluate short and long-term shoulder function after surgical repair in a
      single population of patients in order to follow changes over time. METHODS:
      Thirty-three patients underwent surgery, performed by one surgeon, for the
      treatment of a chronic, symptomatic, full-thickness rotator cuff defect. Data
      were obtained from questionnaires and physical examinations preoperatively, at
      two years, and at ten years. Identical standardized pain and function
      questionnaires were used and clinical evaluation was performed in a consistent
      fashion at all time-periods. The activity level, Constant score, level of
      disability, shoulder function score, and patient's subjective rating of the
      outcome were determined at the time of the final follow-up and compared with the
      same parameters at the two-year follow-up examination in order to determine if
      early results change with time. RESULTS: At the ten-year follow-up examination,
      there was no change in the raw Constant score determined at the two-year
      examination. When the Constant score was normalized for expected age-related
      changes, the percentage of patients who had a satisfactory result at ten years
      was even greater than the percentage at two years. Activity level decreased
      significantly over the time-period (p = 0.005). At the final follow-up
      examination, twelve patients worked at the same occupation as they had when the
      two-year examination was performed, two worked at a less strenuous occupation,
      and the remaining patients were retired. Only two patients retired because of
      problems related to the shoulder. The level of disability decreased over the
      study period, and there was a small improvement in the patients' self-assessment
      shoulder function score. The patients' subjective assessment of the outcome
      remained unchanged. CONCLUSIONS: The results of open rotator cuff repair for
      chronic tears do not deteriorate with time (ten years). The level of disability
      decreases, presumably because of a concurrent decrease in the activity level and
      in the demand on the shoulder as the patient ages. It is important to consider
      age-related changes when assessing the final outcome.

PMID- 11451976
TI  - Oral pentoxifylline inhibits release of tumor necrosis factor-alpha from human
      peripheral blood monocytes : a potential treatment for aseptic loosening of total
      joint components.
AB  - BACKGROUND: Pentoxifylline (Trental) is a methylxanthine-derivative drug that has
      been used for more than twenty years in the treatment of peripheral vascular
      disease. Pentoxifylline is also a potent inhibitor of tumor necrosis factor-alpha
      (TNF-alpha) secretion, both in vitro and in vivo, and has demonstrated efficacy
      in the treatment of certain animal and human inflammatory diseases.
      Pentoxifylline has a potential therapeutic role in the treatment of aseptic
      loosening of total joint replacement components because it inhibits TNF-alpha
      secretion by particle-stimulated human peripheral blood monocytes. The purpose of
      our study was to determine whether the particle-stimulated secretion of TNF-alpha
      by peripheral blood monocytes was inhibited in volunteers who had received
      pentoxifylline orally. METHODS: Human peripheral blood monocytes were harvested
      from eight healthy volunteers and were exposed to three different concentrations
      of titanium particles or to 500 ng/mL of lipopolysaccharide as a positive
      control. The same volunteers were then given pentoxifylline (400 mg, five times
      per day) for seven days. Their peripheral blood monocytes were again isolated and
      exposed to experimental conditions, and the TNF-alpha levels were measured.
      RESULTS: The peripheral blood monocytes from all eight volunteers showed a
      significant reduction in TNF-alpha release following oral treatment with
      pentoxifylline. This reduction was observed at exposures of 10(7) and 10(6)
      titanium particles/mL and in the lipopolysaccharide-treated group, but not at
      10(5) particles/mL. CONCLUSIONS: To our knowledge, this is the first study to
      demonstrate the ability of an oral drug to decrease the release of TNF-alpha from
      human peripheral blood monocytes exposed ex vivo to particle debris. TNF-alpha is
      involved in the pathogenesis of osteolysis and subsequent loosening of total
      joint arthroplasty components. The ability to suppress the release of TNF-alpha
      in patients with a total joint replacement may help to control osteolysis and to
      reduce the development of aseptic loosening. This effect could increase implant
      longevity and decrease the need for revision arthroplasty.

PMID- 11451977
TI  - Effects of the glenoid labrum and glenohumeral abduction on stability of the
      shoulder joint through concavity-compression : an in vitro study.
AB  - BACKGROUND: Although the glenohumeral joint is the most mobile articulation of
      the human body, it is known to exhibit ball-and-socket kinematics. Compression
      into the glenoid labral concavity keeps the humeral head centered. The purpose of
      the present study was to determine the effects of joint position on glenohumeral
      stability through concavity-compression. METHODS: Ten cadaveric shoulders were
      tested. The glenoid was mounted horizontally onto a six-component load-cell while
      the humerus was clamped to a vertically unconstrained slide. An x-y stage
      translated the load-cell with the glenoid underneath the humeral head in eight
      different directions. Compressive loads of 20, 40, and 60 N were applied. The
      tests were repeated in 0 degrees, 30 degrees, 60 degrees, and 90 degrees of
      glenohumeral abduction with and without the labrum. Relative translations between
      the glenoid and the humeral head and the forces resisting translation were
      recorded. Then the stability ratio, defined as the peak translational force
      divided by the applied compressive force, was calculated. RESULTS: The average
      stability ratio was higher in the hanging-arm position than it was in
      glenohumeral abduction. The highest stability ratio was detected in the inferior
      direction (59.8% 7.7%) when the labrum was intact and in the superior direction
      (53.3% 7.9%) when the labrum had been resected. Under both conditions, the
      anterior direction was associated with the lowest stability ratio (32.0% 4.4%
      with the labrum and 30.4% 4.1% without the labrum). Resection of the glenoid
      labrum resulted in an average decrease in the stability ratio of 9.6% 1.7%. With
      increasing compressive load, the average stability ratio slightly decreased.
      CONCLUSIONS: Glenohumeral stability through concavity-compression was greater in
      the hanging-arm position than it was in glenohumeral abduction. The average
      contribution of the labrum to glenohumeral stability through concavity
      compression was approximately 10%, about one-half of the value previously
      reported. With the labrum intact, the glenohumeral joint was most stable in the
      inferior direction. Without the labrum, it was most stable in the superior
      direction. Under both conditions, it was least stable in the anterior direction.
      Glenohumeral joint stability through concavity-compression decreases with higher
      compressive loads.

PMID- 11451978
TI  - Major neurological complications following percutaneous vertebroplasty with
      polymethylmethacrylate : a case report.

PMID- 11451979
TI  - Isolated rupture of the brachialis : a case report.

PMID- 11451980
TI  - Bunionette.
AB  - The bunionette, or tailor's bunion, is a painful osseous prominence on the
      lateral aspect of the head of the fifth metatarsal. This prominence occurs in
      many individuals but seldom causes symptoms. Orthotic devices may be useful if a
      symptomatic bunionette results from excessive pronation of the subtalar joint.
      Operative management to decrease the width of the foot and the osseous prominence
      is indicated when nonoperative treatment can no longer control symptoms and when
      the patient has special demands, particularly in sports. A proximal osteotomy is
      able to correct most deformities. A distal osteotomy is recommended if medial
      translation of the head for one-third of the width of the metatarsal shaft
      produces a normal fourth-fifth intermetatarsal angle.

PMID- 11451982
TI  - Recent socioeconomic trends in orthopaedic practice.

PMID- 11451984
TI  - Early symptoms and diagnosis of bone tumors.

PMID- 11451985
TI  - Maintaining the vastus lateralis attachment in the extended slide trochanteric
      osteotomy.

PMID- 11451986
TI  - Comparison of methods for prediction of lower-extremity growth.

PMID- 11451987
TI  - Abscopal wear debris and total joint arthroplasty: cause for concern?

PMID- 11451988
TI  - Mobile-Bearing versus Fixed-Bearing Knees.

PMID- 11451989
TI  - Prescriber profiles.
AB  - Within a two-week period, two sales representatives from competing pharmaceutical
      companies visited the office of an orthopaedic group practice. One representative
      was elated that the group had been steadily prescribing his company's new
      arthritis medication. The physicians assumed that the representative was speaking
      about the number of sample packs used by their office. Several days later, a
      competing drug representative visited the office and complained that several
      physicians in the group were "not thinking of my company's medication first." The
      physicians were perplexed and asked him how he had come by that information.
      After multiple attempts at evading the question, the representative explained
      that pharmaceutical companies pay the drugstores for such data. Although
      unwilling to disclose the details of the arrangement, he did inform the
      physicians that the pharmaceutical companies know exactly which physicians are
      writing which prescriptions. He assured the physicians that patients' names are
      not disclosed. The physicians spoke to several pharmacists and other
      pharmaceutical representatives, who confirmed the practice.

PMID- 11451990
TI  - What's new in orthopaedic research.

PMID- 11451992
TI  - The human but not the Xenopus RNA-editing enzyme ADAR1 has an atypical nuclear
      localization signal and displays the characteristics of a shuttling protein.
AB  - The RNA-editing enzyme ADAR1 (adenosine deaminase that acts on RNA) is a bona
      fide nuclear enzyme that has been cloned from several vertebrate species.
      Putative nuclear localization signals (NLSs) have been identified in the
      aminoterminal regions of both human and Xenopus ADAR1. Here we show that neither
      of these predicted NLSs is biologically active. Instead, we could identify a
      short basic region located upstream of the RNA-binding domains of Xenopus ADAR1
      to be necessary and sufficient for nuclear import. In contrast, the homologous
      region in human ADAR1 does not display NLS activity. Instead, we could map an NLS
      in human ADAR1 that overlaps with its third double-stranded RNA-binding domain.
      Interestingly, the NLS activity displayed by this double-stranded RNA-binding
      domain does not depend on RNA binding, therefore showing a dual function for this
      domain. Furthermore, nuclear accumulation of human (hs) ADAR1 is transcription
      dependent and can be stimulated by LMB, an inhibitor of Crm1-dependent nuclear
      export, indicating that hsADAR1 can move between the nucleus and cytoplasm.
      Regulated nuclear import and export of hsADAR1 can provide an excellent mechanism
      to control nuclear concentration of this editing enzyme thereby preventing
      hyperediting of structured nuclear RNAs.

PMID- 11451993
TI  - Gamma subunit of the AP-1 adaptor complex binds clathrin: implications for
      cooperative binding in coated vesicle assembly.
AB  - The heterotetrameric AP-1 adaptor complex is involved in the assembly of clathrin
      coated vesicles originating from the trans-Golgi network (TGN). The beta 1
      subunit of AP-1 is known to contain a consensus clathrin binding sequence, LLNLD
      (the so-called clathrin box motif), in its hinge segment through which the beta
      chain interacts with the N-terminal domains of clathrin trimers. Here, we report
      that the hinge region of the gamma subunit of human and mouse AP-1 contains two
      copies of a new variant, LLDLL, of the clathrin box motif that also bind to the
      terminal domain of the clathrin heavy chain. High-affinity binding of the gamma
      hinge to clathrin trimers requires both LLDLL sequences to be present and the
      spacing between them to be maintained. We also identify an independent clathrin
      binding site within the appendage domain of the gamma subunit that interacts with
      a region of clathrin other than the N-terminal domain. Clathrin polymerization is
      promoted by glutathione S-transferase (GST)-gamma hinge, but not by GST-gamma
      appendage. However, the hinge and appendage domains of gamma function in a
      cooperative manner to recruit and polymerize clathrin, suggesting that clathrin
      lattice assembly at the TGN involves multivalent binding of clathrin by the gamma
      and beta1 subunits of AP-1.

PMID- 11451994
TI  - Modulation of cell-substrate adhesion by arachidonic acid: lipoxygenase regulates
      cell spreading and ERK1/2-inducible cyclooxygenase regulates cell migration in
      NIH-3T3 fibroblasts.
AB  - Adhesion of cells to an extracellular matrix is characterized by several discrete
      morphological and functional stages beginning with cell-substrate attachment,
      followed by cell spreading, migration, and immobilization. We find that although
      arachidonic acid release is rate-limiting in the overall process of adhesion, its
      oxidation by lipoxygenase and cyclooxygenases regulates, respectively, the cell
      spreading and cell migration stages. During the adhesion of NIH-3T3 cells to
      fibronectin, two functionally and kinetically distinct phases of arachidonic acid
      release take place. An initial transient arachidonate release occurs during cell
      attachment to fibronectin, and is sufficient to signal the cell spreading stage
      after its oxidation by 5-lipoxygenase to leukotrienes. A later sustained
      arachidonate release occurs during and after spreading, and signals the
      subsequent migration stage through its oxidation to prostaglandins by newly
      synthesized cyclooxygenase-2. In signaling migration, constitutively expressed
      cyclooxygenase-1 appears to contribute approximately 25% of prostaglandins
      synthesized compared with the inducible cyclooxygenase-2. Both the second
      sustained arachidonate release, and cyclooxygenase-2 protein induction and
      synthesis, appear to be regulated by the mitogen-activated protein kinase
      extracellular signal-regulated kinase (ERK)1/2. The initial cell attachment
      induced transient arachidonic acid release that signals spreading through
      lipoxygenase oxidation is not sensitive to ERK1/2 inhibition by PD98059, whereas
      PD98059 produces both a reduction in the larger second arachidonate release and a
      blockade of induced cyclooxygenase-2 protein expression with concomitant
      reduction of prostaglandin synthesis. The second arachidonate release, and
      cyclooxygenase-2 expression and activity, both appear to be required for cell
      migration but not for the preceding stages of attachment and spreading. These
      data suggest a bifurcation in the arachidonic acid adhesion-signaling pathway,
      wherein lipoxygenase oxidation generates leukotriene metabolites regulating the
      spreading stage of cell adhesion, whereas ERK 1/2-induced cyclooxygenase
      synthesis results in oxidation of a later release, generating prostaglandin
      metabolites regulating the later migration stage.

PMID- 11451995
TI  - Topological and mutational analysis of Saccharomyces cerevisiae Ste14p, founding
      member of the isoprenylcysteine carboxyl methyltransferase family.
AB  - Eukaryotic proteins that terminate in a CaaX motif undergo three processing
      events: isoprenylation, C-terminal proteolytic cleavage, and carboxyl
      methylation. In Saccharomyces cerevisiae, the latter step is mediated by Ste14p,
      an integral endoplasmic reticulum membrane protein. Ste14p is the founding member
      of the isoprenylcysteine carboxyl methyltransferase (ICMT) family, whose members
      share significant sequence homology. Because the physiological substrates of
      Ste14p, such as Ras and the yeast a-factor precursor, are isoprenylated and
      reside on the cytosolic side of membranes, the Ste14p residues involved in
      enzymatic activity are predicted to be cytosolically disposed. In this study, we
      have investigated the topology of Ste14p by analyzing the protease protection of
      epitope-tagged versions of Ste14p and the glycosylation status of Ste14p-Suc2p
      fusions. Our data lead to a topology model in which Ste14p contains six membrane
      spans, two of which form a helical hairpin. According to this model most of the
      Ste14p hydrophilic regions are located in the cytosol. We have also generated
      ste14 mutants by random and site-directed mutagenesis to identify residues of
      Ste14p that are important for activity. Notably, four of the five loss-of
      function mutations arising from random mutagenesis alter residues that are highly
      conserved among the ICMT family. Finally, we have identified a novel tripartite
      consensus motif in the C-terminal region of Ste14p. This region is similar among
      all ICMT family members, two phospholipid methyltransferases, several ergosterol
      biosynthetic enzymes, and a group of bacterial open reading frames of unknown
      function. Site-directed and random mutations demonstrate that residues in this
      region play a critical role in the function of Ste14p.

PMID- 11451996
TI  - High PKC alpha and low E-cadherin expression contribute to high migratory
      activity of colon carcinoma cells.
AB  - The protein kinase C (PKC) is a family of serine/threonine kinases that are key
      regulatory enzymes involved in growth, differentiation, cytoskeletal
      reorganization, tumor promotion, and migration. We investigated the functional
      involvement of PKC isotypes and of E-cadherin in the regulation of the locomotion
      of six human colon-adenocarcinoma cell lines. The different levels of the PKC
      alpha and the E-cadherin expression have predictable implications in the
      spontaneous locomotory activity. With the use of PKC alpha--specific inhibitors
      (safingol, Go6976) as well as the PKC delta--specific inhibitor rottlerin, we
      showed that only PKC alpha plays a major role in the regulation of tumor cell
      migration. The results were verified by knocking out the translation of PKC
      isozymes with the use of an antisense oligonucleotide strategy. After stimulation
      with phorbol ester we observed a translocation and a colocalization of the
      activated PKC alpha at the plasma membrane to the surrounding extracellular
      matrix. Furthermore, we investigated the functional involvement of E-cadherin in
      the locomotion with the use of a blocking antibody. A high level of PKC alpha
      expression together with a low E-cadherin expression was strongly related to a
      high migratory activity of the colon carcinoma cells. This correlation was
      independent of the differentiation grade of the tumor cell lines.

PMID- 11451997
TI  - Microtubule disruption in keratinocytes induces cell-cell adhesion through
      activation of endogenous E-cadherin.
AB  - The association of the cytoskeleton with the cadherin--catenin complex is
      essential for strong cell-cell adhesion in epithelial cells. In this study, we
      have investigated the effect of microtubule organization on cell-cell adhesion in
      differentiating keratinocytes. When microtubules of normal human epidermal
      keratinocytes (NHEKs) grown in low calcium media (0.05 mM) were disrupted with
      nocodazole or colcemid, cell-cell adhesion was induced through relocalization of
      the E-cadherin-catenin-actin complex to the cell periphery. This was accompanied
      by actin polymerization. Also, it was found that microtubule disruption-induced
      cell-cell adhesion was significantly reduced in more advanced differentiated
      keratinocytes. For example, when NHEK cells cultured under high calcium (1.2 mM)
      for 8 d and then in low calcium for 1 d were treated with nocodazole, there was
      no induction of cell-cell adhesion. Also long-term treatment of a phorbol ester
      for 48 h inhibited nocodazole-induced cell-cell adhesion of NHEK. Furthermore,
      this nocodazole-induced cell-cell adhesion could be observed in squamous cancer
      cell lines (A431 and SCC-5, -9, and -25) under low calcium condition, but not in
      the keratinocyte cell lines derived from normal epidermis (HaCaT, RHEK). On the
      other hand, HaCaT cells continuously cultivated in low calcium media regained a
      less differentiated phenotype such as decreased expression of cytokeratin 10, and
      increased K5; these changes were accompanied with inducibility of cell-cell
      adhesion by nocodazole. Together, our results suggest that microtubule disruption
      can induce the cell-cell adhesion via activation of endogenous E-cadherin in non-
      or early differentiating keratinocytes. However, this is no longer possible in
      advanced terminally differentiating keratinocytes, possibly due to irreversible
      changes effected by cell envelope barrier formation.

PMID- 11451998
TI  - Microtubule-dependent changes in assembly of microtubule motor proteins and
      mitotic spindle checkpoint proteins at PtK1 kinetochores.
AB  - The ability of kinetochores to recruit microtubules, generate force, and activate
      the mitotic spindle checkpoint may all depend on microtubule- and/or tension
      dependent changes in kinetochore assembly. With the use of quantitative digital
      imaging and immunofluorescence microscopy of PtK1 tissue cells, we find that the
      outer domain of the kinetochore, but not the CREST-stained inner core, exhibits
      three microtubule-dependent assembly states, not directly dependent on tension.
      First, prometaphase kinetochores with few or no kinetochore microtubules have
      abundant punctate or oblate fluorescence morphology when stained for outer domain
      motor proteins CENP-E and cytoplasmic dynein and checkpoint proteins BubR1 and
      Mad2. Second, microtubule depolymerization induces expansion of the kinetochore
      outer domain into crescent and ring morphologies around the centromere. This
      expansion may enhance recruitment of kinetochore microtubules, and occurs with
      more than a 20- to 100-fold increase in dynein and relatively little change in
      CENP-E, BubR1, and Mad2 in comparison to prometaphase kinetochores. Crescents
      disappear and dynein decreases substantially upon microtubule reassembly. Third,
      when kinetochores acquire their full metaphase complement of kinetochore
      microtubules, levels of CENP-E, dynein, and BubR1 decrease by three- to sixfold
      in comparison to unattached prometaphase kinetochores, but remain detectable. In
      contrast, Mad2 decreases by 100-fold and becomes undetectable, consistent with
      Mad2 being a key factor for the "wait-anaphase" signal produced by unattached
      kinetochores. Like previously found for Mad2, the average amounts of CENP-E,
      dynein, or BubR1 at metaphase kinetochores did not change with the loss of
      tension induced by taxol stabilization of microtubules.

PMID- 11451999
TI  - RME-8, a conserved J-domain protein, is required for endocytosis in
      Caenorhabditis elegans.
AB  - By genetic analysis of Caenorhabditis elegans mutants defective in yolk uptake,
      we have identified new molecules functioning in the endocytosis pathway. Here we
      describe a novel J-domain-containing protein, RME-8, identified by such genetic
      analysis. RME-8 is required for receptor-mediated endocytosis and fluid-phase
      endocytosis in various cell types and is essential for C. elegans development and
      viability. In the macrophage-like coelomocytes, RME-8 localizes to the limiting
      membrane of large endosomes. Endocytosis markers taken up by the coelomocytes
      rapidly accumulate in these large RME-8-positive endosomes, concentrate in
      internal subendosomal structures, and later appear in RME-8-negative lysosomes.
      rme-8 mutant coelomocytes fail to accumulate visible quantities of endocytosis
      markers. These observations show that RME-8 functions in endosomal trafficking
      before the lysosome. RME-8 homologues are found in multicellular organisms from
      plants to humans but not in the yeast Saccharomyces cerevisiae. These sequence
      homologies suggest that RME-8 fulfills a conserved function in multicellular
      organisms.

PMID- 11452000
TI  - Telomere dysfunction triggers developmentally regulated germ cell apoptosis.
AB  - Telomere dysfunction results in fertility defects in a number of organisms.
      Although data from fission yeast and Caenorhabditis elegans suggests that
      telomere dysfunction manifests itself primarily as defects in proper meiotic
      chromosome segregation, it is unclear how mammalian telomere dysfunction results
      in germ cell death. To investigate the specific effects of telomere dysfunction
      on mammalian germ cell development, we examined the meiotic progression and germ
      cell apoptosis in late generation telomerase null mice. Our results indicate that
      chromosome asynapsis and missegregation are not the cause of infertility in mice
      with shortened telomeres. Rather, telomere dysfunction is recognized at the onset
      of meiosis, and cells with telomeric defects are removed from the germ cell
      precursor pool. This germ cell telomere surveillance may be an important
      mechanism to protect against the transmission of dysfunctional telomeres and
      chromosomal abnormalities.

PMID- 11452001
TI  - Vaccinia virus DNA replication occurs in endoplasmic reticulum-enclosed
      cytoplasmic mini-nuclei.
AB  - Vaccinia virus (vv), a member of the poxvirus family, is unique among most DNA
      viruses in that its replication occurs in the cytoplasm of the infected host
      cell. Although this viral process is known to occur in distinct cytoplasmic
      sites, little is known about its organization and in particular its relation with
      cellular membranes. The present study shows by electron microscopy (EM) that soon
      after initial vv DNA synthesis at 2 h postinfection, the sites become entirely
      surrounded by membranes of the endoplasmic reticulum (ER). Complete wrapping
      requires ~45 min and persists until virion assembly is initiated at 6 h
      postinfection, and the ER dissociates from the replication sites. [(3)H]Thymidine
      incorporation at different infection times shows that efficient vv DNA synthesis
      coincides with complete ER wrapping, suggesting that the ER facilitates viral
      replication. Proteins known to be associated with the nuclear envelope in
      interphase cells are not targeted to these DNA-surrounding ER membranes, ruling
      out a role for these molecules in the wrapping process. By random green
      fluorescent protein-tagging of vv early genes of unknown function with a putative
      transmembrane domain, a novel vv protein, the gene product of E8R, was identified
      that is targeted to the ER around the DNA sites. Antibodies raised against this
      vv early membrane protein showed, by immunofluorescence microscopy, a
      characteristic ring-like pattern around the replication site. By electron
      microscopy quantitation the protein concentrated in the ER surrounding the DNA
      site and was preferentially targeted to membrane facing the inside of this site.
      These combined data are discussed in relation to nuclear envelope
      assembly/disassembly as it occurs during the cell cycle.

PMID- 11452002
TI  - The Golgi complex is a microtubule-organizing organelle.
AB  - We show that the Golgi complex can directly stimulate microtubule nucleation in
      vivo and in vitro and thus behaves as a potent microtubule-organizing organelle
      in interphase cells. With the use of nocodazole wash-out experiments in hepatic
      cells, we found that the occurrence of noncentrosomal, early stabilized
      microtubules is highly correlated with the subcellular localization of Golgi
      membranes. With the use of in vitro reconstituted microtubule assembly systems
      with or without cytosol, we also found that, in contrast to centrosomally
      attached microtubules, the distal ends of Golgi-attached microtubules are
      remotely stabilized in a way that requires additional cytosolic component(s).
      Finally, we demonstrate that Golgi-based microtubule nucleation is direct and
      involves a subset of gamma-tubulin bound to the cytoplasmic face of the
      organelle.

PMID- 11452003
TI  - Activation of rho GTPases by cytotoxic necrotizing factor 1 induces
      macropinocytosis and scavenging activity in epithelial cells.
AB  - Macropinocytosis, a ruffling-driven process that allows the capture of large
      material, is an essential aspect of normal cell function. It can be either
      constitutive, as in professional phagocytes where it ends with the digestion of
      captured material, or induced, as in epithelial cells stimulated by growth
      factors. In this case, the internalized material recycles back to the cell
      surface. We herein show that activation of Rho GTPases by a bacterial protein
      toxin, the Escherichia coli cytotoxic necrotizing factor 1 (CNF1), allowed
      epithelial cells to engulf and digest apoptotic cells in a manner similar to that
      of professional phagocytes. In particular, we have demonstrated that 1) the
      activation of all Rho, Rac, and Cdc42 by CNF1 was essential for the capture and
      internalization of apoptotic cells; and 2) such activation allowed the discharge
      of macropinosomal content into Rab7 and lysosomal associated membrane protein-1
      acidic lysosomal vesicles where the ingested particles underwent degradation.
      Taken together, these findings indicate that CNF1-induced "switching on" of Rho
      GTPases may induce in epithelial cells a scavenging activity, comparable to that
      exerted by professional phagocytes. The activation of such activity in epithelial
      cells may be relevant, in mucosal tissues, in supporting or integrating the
      scavenging activity of resident macrophages.

PMID- 11452004
TI  - AP-3 mediates tyrosinase but not TRP-1 trafficking in human melanocytes.
AB  - Patients with Hermansky-Pudlak syndrome type 2 (HPS-2) have mutations in the beta
      3A subunit of adaptor complex-3 (AP-3) and functional deficiency of this complex.
      AP-3 serves as a coat protein in the formation of new vesicles, including,
      apparently, the platelet's dense body and the melanocyte's melanosome. We used
      HPS-2 melanocytes in culture to determine the role of AP-3 in the trafficking of
      the melanogenic proteins tyrosinase and tyrosinase-related protein-1 (TRP-1). TRP
      1 displayed a typical melanosomal pattern in both normal and HPS-2 melanocytes.
      In contrast, tyrosinase exhibited a melanosomal (i.e., perinuclear and dendritic)
      pattern in normal cells but only a perinuclear pattern in the HPS-2 melanocytes.
      In addition, tyrosinase exhibited a normal pattern of expression in HPS-2
      melanocytes transfected with a cDNA encoding the beta 3A subunit of the AP-3
      complex. This suggests a role for AP-3 in the normal trafficking of tyrosinase to
      premelanosomes, consistent with the presence of a dileucine recognition signal in
      the C-terminal portion of the tyrosinase molecule. In the AP-3-deficient cells,
      tyrosinase was also present in structures resembling late endosomes or
      multivesicular bodies; these vesicles contained exvaginations devoid of
      tyrosinase. This suggests that, under normal circumstances, AP-3 may act on
      multivesicular bodies to form tyrosinase-containing vesicles destined to fuse
      with premelanosomes. Finally, our studies demonstrate that tyrosinase and TRP-1
      use different mechanisms to reach their premelanosomal destination.

PMID- 11452005
TI  - Evidence for the role of MAP1B in axon formation.
AB  - Cultured neurons obtained from a hypomorphous MAP1B mutant mouse line display a
      selective and significant inhibition of axon formation that reflects a delay in
      axon outgrowth and a reduced rate of elongation. This phenomenon is paralleled by
      decreased microtubule formation and dynamics, which is dramatic at the distal
      axonal segment, as well as in growth cones, where the more recently assembled
      microtubule polymer normally predominates. These neurons also have aberrant
      growth cone formation and increased actin-based protrusive activity. Taken
      together, this study provides direct evidence showing that by promoting
      microtubule dynamics and regulating cytoskeletal organization MAP1B has a crucial
      role in axon formation.

PMID- 11452006
TI  - Endosome to Golgi transport of ricin is independent of clathrin and of the Rab9-
      and Rab11-GTPases.
AB  - The plant toxin ricin is transported to the Golgi and the endoplasmic reticulum
      before translocation to the cytosol where it inhibits protein synthesis. The
      toxin can therefore be used to investigate pathways leading to the Golgi
      apparatus. Except for the Rab9-mediated transport of mannose 6-phosphate
      receptors from endosomes to the trans-Golgi network (TGN), transport routes
      between endosomes and the Golgi apparatus are still poorly characterized. To
      investigate endosome to Golgi transport, we have used here a modified ricin
      molecule containing a tyrosine sulfation site and quantified incorporation of
      radioactive sulfate, a TGN modification. A tetracycline-inducible mutant Rab9S21N
      HeLa cell line was constructed and characterized to study whether Rab9 was
      involved in transport of ricin to the TGN and, if not, to further investigate the
      route used by ricin. Induced expression of Rab9S21N inhibited Golgi transport of
      mannose 6-phosphate receptors but did not affect the sulfation of ricin,
      suggesting that ricin is transported to the TGN via a Rab9-independent pathway.
      Moreover, because Rab11 is present in the endosomal recycling compartment and the
      TGN, studies of transient transfections with mutant Rab11 were performed. The
      results indicated that routing of ricin from endosomes to the TGN occurs by a
      Rab11-independent pathway. Finally, because clathrin has been implicated in early
      endosome to TGN transport, ricin transport was investigated in cells with
      inducible expression of antisense to clathrin heavy chain. Importantly, endosome
      to TGN transport (sulfation of endocytosed ricin) was unchanged when clathrin
      function was abolished. In conclusion, ricin is transported from endosomes to the
      Golgi apparatus by a Rab9-, Rab11-, and clathrin-independent pathway.

PMID- 11452007
TI  - Etoposide induces the dispersal of DNA ligase I from replication factories.
AB  - In eukaryotic cells DNA replication occurs in specific nuclear compartments,
      called replication factories, that undergo complex rearrangements during S-phase.
      The molecular mechanisms underlying the dynamics of replication factories are
      still poorly defined. Here we show that etoposide, an anticancer drug that
      induces double-strand breaks, triggers the redistribution of DNA ligase I and
      proliferating cell nuclear antigen from replicative patterns and the ensuing
      dephosphorylation of DNA ligase I. Moreover, etoposide triggers the formation of
      RPA foci, distinct from replication factories. The effect of etoposide on DNA
      ligase I localization is prevented by aphidicolin, an inhibitor of DNA
      replication, and by staurosporine, a protein kinase inhibitor and checkpoints'
      abrogator. We suggest that dispersal of DNA ligase I is triggered by an intra-S
      phase checkpoint activated when replicative forks meet topoisomerase II-DNA-
      cleavable complexes. However, etoposide treatment of ataxia telangiectasia cells
      demonstrated that ataxia-telangiectasia-mutated activity is not required for the
      disassembly of replication factories and the formation of replication protein A
      foci.

PMID- 11452008
TI  - Alanine-scanning mutagenesis of Aspergillus gamma-tubulin yields diverse and
      novel phenotypes.
AB  - We have created 41 clustered charged-to-alanine scanning mutations of the mipA,
      gamma-tubulin, gene of Aspergillus nidulans and have created strains carrying
      these mutations by two-step gene replacement and by a new procedure, heterokaryon
      gene replacement. Most mutant alleles confer a wild-type phenotype, but others
      are lethal or conditionally lethal. The conditionally lethal alleles exhibit a
      variety of phenotypes under restrictive conditions. Most have robust but highly
      abnormal mitotic spindles and some have abnormal cytoplasmic microtubule arrays.
      Two alleles appear to have reduced amounts of gamma-tubulin at the spindle pole
      bodies and nucleation of spindle microtubule assembly may be partially inhibited.
      One allele inhibits germ tube formation. The cold sensitivity of two alleles is
      strongly suppressed by the antimicrotubule agents benomyl and nocodazole and a
      third allele is essentially dependent on these compounds for growth. Together our
      data indicate that gamma-tubulin probably carries out functions essential to
      mitosis and organization of cytoplasmic microtubules in addition to its well
      documented role in microtubule nucleation. We have also placed our mutations on a
      model of the structure of gamma-tubulin and these data give a good initial
      indication of the functionally important regions of the molecule.

PMID- 11452009
TI  - Activation of Rhoa and ROCK are essential for detachment of migrating leukocytes.
AB  - Detachment of the rear of the cell from its substratum is an important aspect of
      locomotion. The signaling routes involved in this adhesive release are largely
      unknown. One of the few candidate proteins to play a role is RhoA, because
      activation of RhoA in many cell types leads to contraction, a mechanism probably
      involved in detachment. To study the role of RhoA in detachment regulation, we
      analyzed several subsets of expert migratory leukocytes by video microscopy. In
      contrast to fast-migrating neutrophils, eosinophils do not detach the rear of the
      cell unless stimulated with serum. When measuring the amount of active RhoA, with
      the use of a GST-Rhotekin pulldown assay, we found that serum is an excellent
      activator of RhoA in granulocytes. Inhibition of RhoA or one of Rho's target
      proteins, the kinase ROCK, in neutrophils leads to the phenotype seen in
      eosinophils: the rear of the cell is firmly attached to the substratum, whereas
      the cell body is highly motile. ROCK-inhibition leads to impaired migration of
      granulocytes in filters, on glass, and through endothelial monolayers. Also, the
      ROCK signaling pathway is involved in changes of integrin-mediated adhesion.
      Eosinophil transduction by a tat-fusion construct containing active RhoA resulted
      in detachment stimulation in the presence of chemoattractant. From these results
      we conclude that activation of the RhoA-ROCK pathway is essential for detachment
      of migratory leukocytes.

PMID- 11452010
TI  - A genomic study of the bipolar bud site selection pattern in Saccharomyces
      cerevisiae.
AB  - A genome-wide screen of 4168 homozygous diploid yeast deletion strains has been
      performed to identify nonessential genes that participate in the bipolar budding
      pattern. By examining bud scar patterns representing the sites of previous cell
      divisions, 127 mutants representing three different phenotypes were found:
      unipolar, axial-like, and random. From this screen, 11 functional classes of
      known genes were identified, including those involved in actin-cytoskeleton
      organization, general bud site selection, cell polarity, vesicular transport,
      cell wall synthesis, protein modification, transcription, nuclear function,
      translation, and other functions. Four characterized genes that were not known
      previously to participate in bud site selection were also found to be important
      for the haploid axial budding pattern. In addition to known genes, we found 22
      novel genes (20 are designated BUD13-BUD32) important for bud site selection.
      Deletion of one resulted in unipolar budding exclusively from the proximal pole,
      suggesting that this gene plays an important role in diploid distal budding.
      Mutations in 20 other novel BUD genes produced a random budding phenotype and one
      produced an axial-like budding defect. Several of the novel Bud proteins were
      fused to green fluorescence protein; two proteins were found to localize to sites
      of polarized cell growth (i.e., the bud tip in small budded cells and the neck in
      cells undergoing cytokinesis), similar to that postulated for the bipolar signals
      and proteins that target cell division site tags to their proper location in the
      cell. Four others localized to the nucleus, suggesting that they play a role in
      gene expression. The bipolar distal marker Bud8 was localized in a number of
      mutants; many showed an altered Bud8-green fluorescence protein localization
      pattern. Through the genome-wide identification and analysis of different mutants
      involved in bipolar bud site selection, an integrated pathway for this process is
      presented in which proximal and distal bud site selection tags are synthesized
      and localized at their appropriate poles, thereby directing growth at those
      sites. Genome-wide screens of defined collections of mutants hold significant
      promise for dissecting many biological processes in yeast.

PMID- 11452011
TI  - Src family kinases are required for prolactin induction of cell proliferation.
AB  - Prolactin (PRL) is a pleiotropic cytokine promoting cellular proliferation and
      differentiation. Because PRL activates the Src family of tyrosine kinases (SFK),
      we have studied the role of these kinases in PRL cell proliferation signaling.
      PRL induced [(3)H]thymidine incorporation upon transient transfection of BaF-3
      cells with the PRL receptor. This effect was inhibited by cotransfection with the
      dominant negative mutant of c-Src (K>A295/Y>F527, SrcDM). The role of SFK in PRL
      induced proliferation was confirmed in the BaF-3 PRL receptor-stable
      transfectant, W53 cells, where PRL induced Fyn and Lyn activation. The SFK
      selective inhibitors PP1/PP2 and herbimycin A blocked PRL-dependent cell
      proliferation by arresting the W53 cells in G1, with no evident apoptosis. In
      parallel, PP1/PP2 inhibited PRL induction of cell growth-related genes c-fos, c
      jun, c-myc, and odc. These inhibitors have no effect on PRL-mediated activation
      of Ras/Mapk and Jak/Start pathways. In contrast, they inhibited the PRL-dependent
      stimulation of the SFKs substrate Sam68, the phosphorylation of the tyrosine
      phosphatase Shp2, and the PI3K-dependent Akt and p70S6k serine kinases.
      Consistently, transient expression of SrcDM in W53 cells also blocked PRL
      activation of Akt. These results demonstrate that activation of SFKs is required
      for cell proliferation induced by PRL.

PMID- 11452012
TI  - Tubulin sorting during dimerization in vivo.
AB  - We demonstrate sorting of beta-tubulins during dimerization in the Drosophila
      male germ line. Different beta-tubulin isoforms exhibit distinct affinities for
      alpha-tubulin during dimerization. Our data suggest that differences in
      dimerization properties are important in determining isoform-specific microtubule
      functions. The differential use of beta-tubulin during dimerization reveals
      structural parameters of the tubulin heterodimer not discernible in the resolved
      three-dimensional structure. We show that the variable beta-tubulin carboxyl
      terminus, a surface feature in the heterodimer and in microtubules, and which is
      disordered in the crystallographic structure, is of key importance in forming a
      stable alpha-beta heterodimer. If the availability of alpha-tubulin is limiting,
      alpha-beta dimers preferentially incorporate intact beta-tubulins rather than a
      beta-tubulin missing the carboxyl terminus (beta 2 Delta C). When alpha-tubulin
      is not limiting, beta 2 Delta C forms stable alpha-beta heterodimers. Once dimers
      are formed, no further sorting occurs during microtubule assembly: alpha-beta 2
      Delta C dimers are incorporated into axonemes in proportion to their contribution
      to the total dimer pool. Co-incorporation of beta 2 Delta C and wild-type beta 2
      tubulin results in nonmotile axonemes because of a disruption of the periodicity
      of nontubulin axonemal elements. Our data show that the beta-tubulin carboxyl
      terminus has two distinct roles: 1) forming the alpha-beta heterodimer, important
      for all microtubules and 2) providing contacts for nontubulin components required
      for specific microtubule structures, such as axonemes.

PMID- 11452013
TI  - Null mutants of the neurospora actin-related protein 1 pointed-end complex show
      distinct phenotypes.
AB  - Dynactin is a multisubunit complex that regulates the activities of cytoplasmic
      dynein, a microtubule-associated motor. Actin-related protein 1 (Arp1) is the
      most abundant subunit of dynactin, and it forms a short filament to which
      additional subunits associate. An Arp1 filament pointed-end--binding subcomplex
      has been identified that consists of p62, p25, p27, and Arp11 subunits. The
      functional roles of these subunits have not been determined. Recently, we
      reported the cloning of an apparent homologue of mammalian Arp11 from the
      filamentous fungus Neurospora crassa. Here, we report that N. crassa ro-2 and ro
      12 genes encode the respective p62 and p25 subunits of the pointed-end complex.
      Characterization of Delta ro-2, Delta ro-7, and Delta ro-12 mutants reveals that
      each has a distinct phenotype. All three mutants have reduced in vivo vesicle
      trafficking and have defects in vacuole distribution. We showed previously that
      in vivo dynactin function is required for high-level dynein ATPase activity, and
      we find that all three mutants have low dynein ATPase activity. Surprisingly,
      Delta ro-12 differs from Delta ro-2 and Delta ro-7 and other previously
      characterized dynein/dynactin mutants in that it has normal nuclear distribution.
      Each of the mutants shows a distinct dynein/dynactin localization pattern. All
      three mutants also show stronger dynein/dynactin-membrane interaction relative to
      wild type, suggesting that the Arp1 pointed-end complex may regulate interaction
      of dynactin with membranous cargoes.

PMID- 11452014
TI  - Differential control of transcription by DNA-bound cyclins.
AB  - Different cyclins mediate different cell-cycle transitions. Some cyclins, such as
      cyclin A and cyclin E, form stable complexes with proteins that bind directly or
      indirectly to DNA and thus might be recruited to certain regions of the genome at
      specific times in the cell cycle. Furthermore, cyclins contain structural motifs
      that are also present in known transcriptional modulators. We found that cyclin A
      is a potent transcriptional repressor and cyclin E is a potent transcriptional
      activator when bound to DNA via a heterologous DNA binding domain. The former
      activity was linked to the integrity of the cyclin A cyclin fold, whereas the
      latter activity related to the ability of cyclin E to activate cdk2 and recognize
      substrates. Furthermore, we found that cyclin E, but not cyclin A, activated
      transcription in a cell-cycle-dependent manner when present in physiological
      concentrations as an unfused protein. These results suggest that cyclin A and
      cyclin E intrinsically differ with respect to their ability to modulate
      transcription when tethered to DNA.

PMID- 11452015
TI  - Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5
      when physically associated in a complex.
AB  - Rab GTPases are central elements of the vesicular transport machinery. An
      emerging view is that downstream effectors of these GTPases are multiprotein
      complexes that include nucleotide exchange factors to ensure coupling between
      GTPase activation and effector function. We have previously shown that Rab5,
      which regulates various steps of transport along the early endocytic pathway, is
      activated by a complex consisting of Rabex-5, a Rab5 nucleotide exchange factor,
      and the effector Rabaptin-5. We postulated that the physical association of these
      two proteins is necessary for their activity in Rab5-dependent endocytic membrane
      transport. To evaluate the functional implications of such complex formation, we
      have reconstituted it with the use of recombinant proteins and characterized its
      properties. First, we show that Rabaptin-5 increases the exchange activity of
      Rabex-5 on Rab5. Second, Rab5-dependent recruitment of Rabaptin-5 to early
      endosomes is completely dependent on its physical association with Rabex-5.
      Third, complex formation between Rabaptin-5 and Rabex-5 is essential for early
      endosome homotypic fusion. These results reveal a functional synergy between
      Rabaptin-5 and Rabex-5 in the complex and have implications for the function of
      analogous complexes for Rab and Rho GTPases.

PMID- 11452016
TI  - Estrogen receptor interaction with estrogen response elements.
AB  - The estrogen receptor (ER) is a ligand-activated enhancer protein that is a
      member of the steroid/nuclear receptor superfamily. Two genes encode mammalian
      ER: ERalpha and ERbeta. ER binds to specific DNA sequences called estrogen
      response elements (EREs) with high affinity and transactivates gene expression in
      response to estradiol (E(2)). The purpose of this review is to summarize how
      natural and synthetic variations in the ERE sequence impact the affinity of ER
      ERE binding and E(2)-induced transcriptional activity. Surprisingly, although the
      consensus ERE sequence was delineated in 1989, there are only seven natural EREs
      for which both ERalpha binding affinity and transcriptional activation have been
      examined. Even less information is available regarding how variations in ERE
      sequence impact ERbeta binding and transcriptional activity. Review of data from
      our own laboratory and those in the literature indicate that ERalpha binding
      affinity does not relate linearly with E(2)-induced transcriptional activation.
      We suggest that the reasons for this discord include cellular amounts of
      coactivators and adaptor proteins that play roles both in ER binding and
      transcriptional activation; phosphorylation of ER and other proteins involved in
      transcriptional activation; and sequence-specific and protein-induced alterations
      in chromatin architecture.

PMID- 11452017
TI  - Asymmetrically distributed oligonucleotide repeats in the Caenorhabditis elegans
      genome sequence that map to regions important for meiotic chromosome segregation.
AB  - The roundworm Caenorhabditis elegans has a haploid karyotype containing six
      linear chromosomes. The termini of worm chromosomes have been proposed to play an
      important role in meiotic prophase, either when homologs are participating in a
      genome-wide search for their proper partners or in the initiation of synapsis.
      For each chromosome one end appears to stimulate crossing-over with the correct
      homolog; the other end lacks this property. We have used a bioinformatics
      approach to identify six repetitive sequence elements in the sequenced C.elegans
      genome whose distribution closely parallels these putative meiotic pairing
      centers (MPC) or homolog recognition regions (HRR). We propose that these six DNA
      sequence elements, which are largely chromosome specific, may correspond to the
      genetically defined HRR/MPC elements.

PMID- 11452018
TI  - Temperature sensitive nop2 alleles defective in synthesis of 25S rRNA and large
      ribosomal subunits in Saccharomyces cerevisiae.
AB  - Using molecular genetic techniques, we have generated and characterized six
      temperature sensitive (ts) alleles of nop2. All failed to support growth at 37
      degrees C and one was also formamide sensitive (fs) and failed to grow on media
      containing 3% formamide. Conditional lethality is not due to rapid turnover of
      mutant Nop2p proteins at 37 degrees C. Each allele contains between seven and 14
      amino acid substitutions and one possesses a nonsense mutation near the C
      terminus. Mapping experiments with one allele, nop2-4, revealed that a subset of
      the amino acid substitutions conferred the ts phenotype and that these mutations
      have an additive effect. All six mutants exhibited dramatic reductions in levels
      of 60S ribosome subunits under non-permissive conditions as well as some
      reduction at permissive temperature. Processing of 27S pre-rRNA to mature 25S
      rRNA was defective in all six mutants grown under non-permissive conditions.
      Levels of the 40S ribosomal subunit and 18S rRNA were not significantly affected.
      Amino acid substitutions in nop2 conditional alleles are discussed in the context
      of the hypothesis that Nop2p functions both as an RNA methyltransferase and a
      trans-acting factor in rRNA processing and large ribosomal subunit biogenesis.

PMID- 11452019
TI  - Nucleolar protein Nop12p participates in synthesis of 25S rRNA in Saccharomyces
      cerevisiae.
AB  - A genetic screen for mutations synthetically lethal with temperature sensitive
      alleles of nop2 led to the identification of the nucleolar proteins Nop12p and
      Nop13p in Saccharomyces cerevisiae. NOP12 was identified by complementation of a
      synthetic lethal growth phenotype in strain YKW35, which contains a single
      nonsense mutation at codon 359 in an allele termed nop12-1. Database mining
      revealed that Nop12p was similar to a related protein, Nop13p. Nop12p and Nop13p
      are not essential for growth and each contains a single canonical RNA recognition
      motif (RRM). Both share sequence similarity with Nsr1p, a previously identified,
      non-essential, RRM-containing nucleolar protein. Likely orthologs of Nop12p were
      identified in Drosophila and Schizosaccharomyces pombe. Deletion of NOP12
      resulted in a cold sensitive (cs) growth phenotype at 15 degrees C and slow
      growth at 20 and 25 degrees C. Growth of a nop12Delta strain at 15 and 20 degrees
      C resulted in impaired synthesis of 25S rRNA, but not 18S rRNA. A nop13 null
      strain did not produce an observable growth phenotype under the laboratory
      conditions examined. Epitope-tagged Nop12p, which complements the cs growth
      phenotype and restores normal 25S rRNA levels, was localized to the nucleolus by
      immunofluorescence microscopy. Epitope-tagged Nop13p was distributed primarily in
      the nucleolus, with a lesser portion localizing to the nucleoplasm. Thus, Nop12p
      is a novel nucleolar protein required for pre-25S rRNA processing and normal
      rates of cell growth at low temperatures.

PMID- 11452020
TI  - Cloning and characterization of two guide RNA-binding proteins from mitochondria
      of Crithidia fasciculata: gBP27, a novel protein, and gBP29, the orthologue of
      Trypanosoma brucei gBP21.
AB  - In kinetoplastid protozoa, mitochondrial (mt) mRNAs are post-transcriptionally
      edited by insertion and deletion of uridylate residues, the information being
      provided by guide (g)RNAs. Currently popular mechanisms for the editing process
      envisage a series of consecutive 'cut-and-paste' reactions, carried out by a
      complex RNP machinery. Here we report on the purification, cloning and functional
      analysis of two gRNA-binding proteins of 28.8 (gBP29) and 26.8 kDa (gBP27) from
      mitochondria of the insect trypanosome Crithidia fasciculata. gBP29 and gBP27
      proved to be similar, Arg + Ala-rich proteins, with pI values of approximately
      10.0. gBP27 has no homology to known proteins, but gBP29 is the C.fasciculata
      orthologue of gBP21 from Trypanosoma brucei, a gRNA-binding protein that
      associates with active RNA editing complexes. As measured in UV cross-linking
      assays, His-tagged recombinant gBP29 and gBP27 bind to radiolabelled poly(U) and
      synthetic gRNAs, while competition experiments suggest a role for the gRNA 3'-(U)
      tail in binding to these proteins. Immunoprecipitates of mt extracts generated
      with antibodies against gBP29 also contained gBP27 and vice versa. The
      immunoprecipitates further harbored a large proportion of the cellular content of
      four different gRNAs and of edited and pre-edited NADH dehydrogenase subunit 7
      mRNAs, but only small amounts of mt rRNAs. In addition, the bulk of gBP29 and
      gBP27 co-eluted with gRNAs from gel filtration columns in the high molecular
      weight range. Together, these results suggest that the proteins are part of a
      large macromolecular complex(es). We infer that gBP29 and gBP27 are components of
      the C.fasciculata editing machinery that may interact with gRNAs.

PMID- 11452021
TI  - Involvement of Schizosaccharomyces pombe Srs2 in cellular responses to DNA
      damage.
AB  - In the budding yeast Saccharomyces cerevisiae the Srs2/RadH DNA helicase promotes
      survival after ultraviolet (UV) irradiation, and has been implicated in DNA
      repair, recombination and checkpoint signalling following DNA damage. A second
      helicase, Sgs1, is the S.cerevisiae homologue of the human BLM and WRN proteins,
      which are defective in cancer predisposition and/or premature ageing syndromes.
      Saccharomyces cerevisiae cells lacking both Srs2 and Sgs1 exhibit a severe growth
      defect. We have identified an Srs2 orthologue in the fission yeast
      Schizosaccharomyces pombe, and have investigated its role in responses to UV
      irradiation and inhibition of DNA replication. Deletion of fission yeast srs2
      caused spontaneous hyper-recombination and UV sensitivity, and simultaneous
      deletion of the SGS1 homologue rqh1 caused a severe growth defect reminiscent of
      that seen in the equivalent S.cerevisiae mutant. However, unlike in budding
      yeast, inactivation of the homologous recombination pathway did not suppress this
      growth defect. Indeed, the homologous recombination pathway was required for
      maintenance of normal fission yeast viability in the absence of Srs2, and loss of
      homologous recombination and loss of Srs2 contributed additively to UV
      sensitivity. We conclude that Srs2 plays related, but not identical, roles in the
      two yeast species.

PMID- 11452022
TI  - Solution structure of a DNA duplex with a chiral alkyl phosphonate moiety.
AB  - The solution structures of two DNA decamers of sequence
      d(CCACCpxGGAAC).(GTTCCGGTGG) with a chiral alkyl phosphonate moiety (px) have
      been determined using NMR and restrained molecular dynamics simulations and
      compared with the solution structure of the unmodified duplex. The (1)H NMR
      spectra of two samples with pure stereochemistry in the modified phosphate have
      been assigned. The structures of both diastereoisomers, as well as the unmodified
      control duplex, have been determined from NMR-derived distance and torsion angle
      constraints. Accurate distance constraints were obtained from a complete
      relaxation matrix analysis of the NOE intensities. The structures have been
      refined with state of the art molecular dynamics methods, including explicit
      solvent and applying the particle mesh Ewald method to properly evaluate the long
      range electrostatic interactions. In both cases, the calculations converge to
      well-defined structures, with RMSDs of approximately 1 A. The resulting
      structures belong to the general B family of DNA structures, even though the
      presence of the alkyl phosphonate moiety induces some slight displacement to the
      A-form in the neighborhood of the modified phosphate. Partial neutralization of
      this phosphate and the steric effect of the alkyl moiety provoke moderate bending
      in the DNA. This effect is more pronounced in the S diastereoisomer, where the
      alkyl group points inwards to the double helix.

PMID- 11452023
TI  - Biochemical characterization of the small isoform of Drosophila melanogaster
      RECQ5 helicase.
AB  - Recently the gene encoding a member of the RecQ helicase family, RecQ5, was
      cloned from the fruit fly, Drosophila melanogaster [J.J.Sekelsky, M.H.Brodsky,
      G.M. Rubin and R.S. Hawley (1999) Nucleic Acids Res., 27, 3762-3769]. The
      Drosophila RecQ5 transcript is alternatively spliced, like its human counterpart,
      to yield three protein isoforms. Two of these isoforms are almost identical and
      have a predicted molecular weight of 54 kDa. The third isoform is larger and
      contains, in addition to the helicase domain shared by all three isoforms, a long
      highly charged C-terminal region. A small isoform of the Drosophila RecQ5 protein
      (RECQ5) has been expressed in Escherichia coli and purified. The purified protein
      is a single-stranded DNA-stimulated ATPase (dATPase) and a 3'-->5' DNA helicase.
      Hydrolysis of the nucleotide cofactor is required for unwinding activity and dATP
      supported the unwinding reaction better than other NTPs. The turnover number for
      the single-stranded DNA-stimulated dATPase activity was 1380 min(-1),
      approximately 1.5-fold higher than that observed for the ATPase activity (900
      min(-1)). The purified protein catalyzed unwinding of partial duplex substrates
      up to at least 93 bp, however, unwinding of an 89 bp blunt duplex substrate was
      not detected.

PMID- 11452024
TI  - Improving the accuracy of PSI-BLAST protein database searches with composition
      based statistics and other refinements.
AB  - PSI-BLAST is an iterative program to search a database for proteins with distant
      similarity to a query sequence. We investigated over a dozen modifications to the
      methods used in PSI-BLAST, with the goal of improving accuracy in finding true
      positive matches. To evaluate performance we used a set of 103 queries for which
      the true positives in yeast had been annotated by human experts, and a popular
      measure of retrieval accuracy (ROC) that can be normalized to take on values
      between 0 (worst) and 1 (best). The modifications we consider novel improve the
      ROC score from 0.758 +/- 0.005 to 0.895 +/- 0.003. This does not include the
      benefits from four modifications we included in the 'baseline' version, even
      though they were not implemented in PSI-BLAST version 2.0. The improvement in
      accuracy was confirmed on a small second test set. This test involved analyzing
      three protein families with curated lists of true positives from the non
      redundant protein database. The modification that accounts for the majority of
      the improvement is the use, for each database sequence, of a position-specific
      scoring system tuned to that sequence's amino acid composition. The use of
      composition-based statistics is particularly beneficial for large-scale automated
      applications of PSI-BLAST.

PMID- 11452025
TI  - Telomerase activation by histone deacetylase inhibitor in normal cells.
AB  - Although telomerase activity is known to be regulated mainly at the level of
      transcription of the human telomerase catalytic subunit (hTERT) gene, the
      molecular mechanism underlying tumor-specific expression of telomerase remains
      unclear. Emerging evidence suggests that reversible acetylation of nucleosomal
      histones and the resultant changes in the chromatin structure are important
      processes in gene transcription. In particular, histone deacetylase (HDAC)
      inhibitors activate the transcription of certain genes by altering the
      acetylation status of nucleosomal histones. The present study examines the
      effects of HDAC inhibitor on hTERT gene transcription. Treatment with tricostatin
      A (TSA) induced significant activation of hTERT mRNA expression and telomerase
      activity in normal cells, but not in cancer cells. Transient expression assays
      revealed that TSA activates the hTERT promoter. Furthermore, the proximal 181 bp
      core promoter of hTERT, which contains two c-Myc and five Sp1 sites, was
      determined to be the responsible element. Overexpression of Sp1 enhanced
      responsiveness to TSA, and mutation of Sp1 sites, but not c-Myc sites, of the
      core promoter of hTERT abrogated this activation. Introduction of the dominant
      negative form of the Sp family inhibited TSA activation. These results indicate
      that HDAC inhibitor activates the hTERT promoter in normal cells, in which Sp1
      plays a key role. This finding suggests one way whereby histone deacetylation may
      be involved in silencing the hTERT gene in normal cells.

PMID- 11452026
TI  - Functionally antagonistic sequences are required for normal autoregulation of
      Drosophila tra-2 pre-mRNA splicing.
AB  - Expression of functional TRA-2 protein in the male germline of Drosophila is
      regulated through a negative feedback mechanism in which a specific TRA-2 isoform
      represses splicing of the M1 intron in the TRA-2 pre-mRNA. We have previously
      shown that the mechanism of M1 splicing repression is conserved between distantly
      related Drosophila species. Using transgenic fly strains, we have examined the
      effects on regulation of mutations in two conserved features of the M1 intron.
      Our results show that TRA-2-dependent repression of M1 splicing depends on the
      presence of a suboptimal non-consensus 3' splice site. Substitution of this 3'
      splice site with a strong splice site resulted in TRA-2 independent splicing,
      while substitution with an unrelated weak 3' splice site was compatible with
      repression, implying that reduced basal splicing efficiency is important for
      regulation. A second conserved element internal to the intron was found to be
      essential for efficient M1 splicing in the soma where the intron is not normally
      retained. We show that the role of this element is to enhance splicing and
      overcome the reduction in efficiency caused by the intron's suboptimal 3' splice
      site. Our results indicate that antagonistic elements in the M1 intron act
      together to establish a context that is permissive for repression of splicing by
      TRA-2 while allowing efficient splicing in the absence of a repressor.

PMID- 11452027
TI  - Phosphorylation of the RNA-dependent protein kinase regulates its RNA-binding
      activity.
AB  - The RNA-dependent protein kinase (PKR) is an interferon-induced, RNA-activated
      enzyme that phosphorylates the alpha-subunit of eukaryotic initiation factor 2
      (eIF2alpha), inhibiting the function of the eIF2 complex and continued initiation
      of translation. When bound to an activating RNA and ATP, PKR undergoes
      autophosphorylation reactions at multiple serine and threonine residues. This
      autophosphorylation reaction stimulates the eIF2alpha kinase activity of PKR. The
      binding of certain viral RNAs inhibits the activation of PKR. Wild-type PKR is
      obtained as a highly phosphorylated protein when overexpressed in Escherichia
      coli. We report here that treatment of the isolated phosphoprotein with the
      catalytic subunit of protein phosphatase 1 dephosphorylates the enzyme. The in
      vitro autophosphorylation and eIF2alpha kinase activities of the dephosphorylated
      enzyme are stimulated by addition of RNA. Thus, inactivation by phosphatase
      treatment of autophosphorylated PKR obtained from overexpression in bacteria
      generates PKR in a form suitable for in vitro analysis of the RNA-induced
      activation mechanism. Furthermore, we used gel mobility shift assays,
      methidiumpropyl-EDTA.Fe footprinting and affinity chromatography to demonstrate
      differences in the RNA-binding properties of phospho- and dephosphoPKR. We found
      that dephosphorylation of PKR increases binding affinity of the enzyme for both
      kinase activating and inhibiting RNAs. These results are consistent with an
      activation mechanism that includes release of the activating RNA upon
      autophosphorylation of PKR prior to phosphorylation of eIF2alpha.

PMID- 11452028
TI  - Expression of hsp16 in response to nucleotide depletion is regulated via the spc1
      MAPK pathway in Schizosaccharomyces pombe.
AB  - A universal response to elevated temperature and other forms of physiological
      stress is the induction of heat shock proteins (HSPs). Hsp16 in
      Schizosaccharomyces pombe encodes a polypeptide of predicted molecular weight 16
      kDa that belongs to the HSP20/alpha-crystallin family whose members range in size
      from 12 to 43 kDa. Heat shock treatment increases expression of the hsp16 gene by
      64-fold in wild-type cells and 141-fold in cdc22-M45 (ribonucleotide reductase)
      mutant cells. Hsp16 expression is mediated by the spc1 MAPK signaling pathway
      through the transcription factor atf1 and in addition through the HSF pathway.
      Nucleotide depletion or DNA damage as occurs in cdc22-M45 mutant cells, or during
      hydroxyurea or camptothecin treatment, is sufficient to activate hsp16 expression
      through atf1. Our findings suggest a novel role for small HSPs in the stress
      response following nucleotide depletion and DNA damage. This extends the types of
      damage that are sensed by the spc1 MAPK pathway via atf1.

PMID- 11452029
TI  - Genomic cloning of the Hsc71 gene in the hermaphroditic teleost Rivulus
      marmoratus and analysis of its expression in skeletal muscle: identification of a
      novel muscle-preferred regulatory element.
AB  - To further our understanding of the role of stress proteins in development as
      well as in adaptation of fish to adverse environmental conditions, we undertook
      molecular analyses of stress protein encoding genes from the hermaphroditic
      teleost Rivulus marmoratus. We isolated a genomic clone containing the Hsc71 gene
      (rm-hsc71m) and its upstream sequences. rm-Hsc71m is not induced by external
      stress, but is enriched in a tissue-specific manner during early development. In
      adult, the strongest expression appeared in skeletal muscle, whereas lower
      expression was seen in the gill, eye and brain. To understand the regulatory
      basis of high muscle expression of rm-hsc71m, transfection of R.marmoratus muscle
      tissue was performed using 5' deletion fragments containing the rm-hsc71m
      promoter driving EGFP expression. An upstream region from -2.7 to -1.9 kb was
      identified as a muscle-specific regulatory region. Within this region, we
      identified at least three sites with the novel sequence TGTnACA interacting with
      a fish muscle factor having an M(r) of 32 000. Our data indicate that rm-hsc71m
      expression in skeletal muscle is controlled by a muscle-specific regulatory
      element containing this novel motif.

PMID- 11452030
TI  - Oligonucleotides form a duplex with non-helical properties on a positively
      charged surface.
AB  - The double helix is known to form as a result of hybridization of complementary
      nucleic acid strands in aqueous solution. In the helix the negatively charged
      phosphate groups of each nucleic acid strand are distributed helically on the
      outside of the duplex and are available for interaction with cationic groups.
      Cation-coated glass surfaces are now widely used in biotechnology, especially for
      covalent attachment of cDNAs and oligonucleotides as surface-bound probes on
      microarrays. These cationic surfaces can bind the nucleic acid backbone
      electrostatically through the phosphate moiety. Here we describe a simple method
      to fabricate DNA microarrays based upon adsorptive rather than covalent
      attachment of oligonucleotides to a positively charged surface. We show that such
      adsorbed oligonucleotide probes form a densely packed monolayer, which retains
      capacity for base pair-specific hybridization with a solution state DNA target
      strand to form the duplex. However, both strand dissociation kinetics and the
      rate of DNase digestion suggest, on symmetry grounds, that the target DNA binds
      to such adsorbed oligonucleotides to form a highly asymmetrical and unwound
      duplex. Thus, it is suggested that, at least on a charged surface, a non-helical
      DNA duplex can be the preferred structural isomer under standard biochemical
      conditions.

PMID- 11452031
TI  - Characterisation of the structure of ocr, the gene 0.3 protein of bacteriophage
      T7.
AB  - The product of gene 0.3 of bacteriophage T7, ocr, is a potent inhibitor of type I
      DNA restriction and modification enzymes. We have used biophysical methods to
      examine the mass, stability, shape and surface charge distribution of ocr. Ocr is
      a dimeric protein with hydrodynamic behaviour equivalent to a prolate ellipsoid
      of axial ratio 4.3 +/- 0.7:1 and mass of 27 kDa. The protein is resistant to
      denaturation but removal of the C-terminal region reduces stability
      substantially. Six amino acids, N4, D25, N43, D62, S68 and W94, are all located
      on the surface of the protein and N4 and S68 are also located at the interface
      between the two 116 amino acid monomers. Negatively charged amino acid side
      chains surround W94 but these side chains are not part of the highly acidic C
      terminus after W94. Ocr is able to displace a short DNA duplex from the binding
      site of a type I enzyme with a dissociation constant of the order of 100 pM or
      better. These results suggest that ocr is of a suitable size and shape to
      effectively block the DNA binding site of a type I enzyme and has a large
      negatively charged patch on its surface. This charge distribution may be
      complementary to the charge distribution within the DNA binding site of type I
      DNA restriction and modification enzymes.

PMID- 11452032
TI  - Tripartite structure of Saccharomyces cerevisiae Dna2 helicase/endonuclease.
AB  - In order to gain insights into the structural basis of the multifunctional Dna2
      enzyme involved in Okazaki fragment processing, we performed biochemical,
      biophysical and genetic studies to dissect the domain structure of Dna2.
      Proteolytic digestion of Dna2 using subtilisin produced a 127 kDa polypeptide
      that lacked the 45 kDa N-terminal region of Dna2. Further digestion generated two
      subtilisin-resistant core fragments of approximately equal size, 58 and 60 kDa.
      Surprisingly, digestion resulted in a significant (3- to 8-fold) increase in both
      ATPase and endonuclease activities compared to the intact enzyme. However, cells
      with a mutant DNA2 allele lacking the corresponding N-terminal region were
      severely impaired in growth, being unable to grow at 37 degrees C, indicating
      that the N-terminal region contains a domain critical for a cellular function(s)
      of Dna2. Analyses of the hydrodynamic properties of and in vivo complex formation
      by wild-type and/or mutant Dna2 lacking the N-terminal 45 kDa domain revealed
      that Dna2 is active as the monomer and thus the defect in the mutant Dna2 protein
      is not due to its inability to multimerize. In addition, we found that the N
      terminal 45 kDa domain interacts physically with a central region located between
      the two catalytic domains. Our results suggest that the N-terminal 45 kDa domain
      of Dna2 plays a critical role in regulation of the enzymatic activities of Dna2
      by serving as a site for intra- and intermolecular interactions essential for
      optimal function of Dna2 in Okazaki fragment processing. The possible mode of
      regulation of Dna2 is discussed based upon our recent finding that replication
      protein A interacts functionally and physically with Dna2 during Okazaki fragment
      processing.

PMID- 11452033
TI  - Deletion of the CSB homolog, RAD26, yields Spt(-) strains with proficient
      transcription-coupled repair.
AB  - It has been previously shown that disruption of RAD26 in yeast strain W303-1B
      results in a strain that is deficient in transcription-coupled repair (TCR), the
      preferential repair of the transcribed strand of an expressed gene over the non
      transcribed strand and the rest of the genome. RAD26 encodes a protein that is
      homologous to Cockayne syndrome group B protein (CSB) and is a member of the
      SWI2/SNF2 family of DNA-dependent ATPases involved in chromatin remodeling. Like
      the rad26 mutant, cells from Cockayne syndrome patients are defective in TCR. We
      examined the role of Rad26 in TCR by disrupting RAD26 in two repair-proficient
      laboratory strains and, remarkably, observed no effect upon TCR. Our results
      indicate that disruption of RAD26 alone is insufficient to impair TCR. Thus, W303
      1B must already possess a mutation that, together with disruption of RAD26,
      causes a deficiency in TCR. We suggest that other genes are mutated in Cockayne
      syndrome cells that contribute to the deficiency in TCR. Surprisingly, deletion
      of RAD26 results in expression of genes that are repressed by flanking transposon
      delta elements, an Spt(-) phenotype. The delta elements appear to perturb local
      chromatin structure. Expression of genes flanked by delta elements in rad26Delta
      mutants is consistent with a role for Rad26 in chromatin remodeling.

PMID- 11452034
TI  - Regulation of CCAAT/enhancer-binding protein-beta isoform synthesis by
      alternative translational initiation at multiple AUG start sites.
AB  - The mRNA of the intronless, single-copy CCAAT/enhancer-binding protein-beta
      (C/EBPbeta) gene encodes several isoforms that have truncated transcription
      activation domains. This occurs by the alternative translational initiation (ATI)
      at multiple AUG start sites. The C/EBPbeta mRNA has four in-frame AUGs and an
      internal out-of-frame AUG associated with a small open reading frame (sORF).
      Initiation of translation at the in-frame AUGs forms 40-kDa (AUG-1), 35-kDa (AUG
      2), 20-kDa (AUG-3) and 8.5-kDa (AUG-4) isoforms. We show that in COS-1 cells the
      20-kDa isoform is not a product of proteolysis of the higher molecular weight
      isoforms. The sORF contains an AUG and termination signal that may produce the
      oligopeptide MPPAAARRL. Our studies suggest that ATI involves three mRNA
      structural features: (i) the cap structure, (ii) the context of the Kozak
      sequences that flank the AUG and (iii) the integrity of the sORF. We propose that
      formation of C/EBPbeta isoforms is accomplished by a leaky ribosomal scanning
      mechanism that facilitates ATI of multiple internal AUGs.

PMID- 11452035
TI  - Biochemical characterization of a novel hypoxanthine/xanthine dNTP
      pyrophosphatase from Methanococcus jannaschii.
AB  - A novel dNTP pyrophosphatase, Mj0226 from Methanococcus jannaschii, which
      catalyzes the hydrolysis of nucleoside triphosphates to the monophosphate and
      PPi, has been characterized. Mj0226 protein catalyzes hydrolysis of two major
      substrates, dITP and XTP, suggesting that the 6-keto group of hypoxanthine and
      xanthine is critical for interaction with the protein. Under optimal reaction
      conditions the k(ca)(t) /K(m) value for these substrates was approximately 10 000
      times that with dATP. Neither endonuclease nor 3'-exonuclease activities were
      detected in this protein. Interestingly, dITP was efficiently inserted opposite a
      dC residue in a DNA template and four dNTPs were also incorporated opposite a
      hypoxanthine residue in template DNA by DNA polymerase I. Two protein homologs of
      Mj0226 from Escherichia coli and Archaeoglobus fulgidus were also cloned and
      purified. These have catalytic activities similar to Mj0226 protein under optimal
      conditions. The implications of these results have significance in understanding
      how homologous proteins, including Mj0226, act biologically in many organisms. It
      seems likely that Mj0226 and its homologs have a major role in preventing
      mutations caused by incorporation of dITP and XTP formed spontaneously in the
      nucleotide pool into DNA. This report is the first identification and functional
      characterization of an enzyme hydrolyzing non-canonical nucleotides, dITP and
      XTP.

PMID- 11452036
TI  - Localization of an exonic splicing enhancer responsible for mammalian natural
      trans-splicing.
AB  - Carnitine octanoyltransferase (COT) produces three different transcripts in rat
      through cis- and trans-splicing reactions, which may lead to the synthesis of two
      proteins. Generation of the three COT transcripts in rat does not depend on sex,
      development, fat feeding, the inclusion of the peroxisome proliferator
      diethylhexyl phthalate in the diet or hyperinsulinemia. In addition, trans
      splicing was not detected in COT of other mammals, such as human, pig, cow and
      mouse, or in Cos7 cells from monkey. Rat COT exon 2 contains two purine-rich
      sequences. Mutation of the rat COT exon 2 upstream box does not affect the trans
      splicing in vitro between two truncated constructs containing exon 2 and its
      adjacent intron boundaries. In contrast, mutation of the downstream box from the
      rat sequence (GAAGAAG) to a random sequence or the sequence observed in the other
      mammals (AAAAAAA) decreased trans-splicing in vitro. In contrast, mutation of the
      AAAAAAA box of human COT exon 2 to GAAGAAG increases trans-splicing. Heterologous
      reactions between COT exon 2 from rat and human do not produce trans-splicing.
      HeLa cells transfected with minigenes of rat COT sequences produced cis- and
      trans-spliced bands. Mutation of the GAAGAAG box to AAAAAAA abolished trans
      splicing and decreased cis-splicing in vivo. We conclude that GAAGAAG is an
      exonic splicing enhancer that could induce natural trans-splicing in rat COT.

PMID- 11452037
TI  - Activation of APE/Ref-1 redox activity is mediated by reactive oxygen species and
      PKC phosphorylation.
AB  - Reactive oxygen species (ROS) arise through normal cellular aerobic respiration,
      and, in combination with external sources such as ionizing radiation, cigarette
      tar and smoke, and particulate matter generated by combustion, can have a
      profound negative effect on cellular macromolecules such as DNA that may lead to
      a number of human pathological disorders including accelerated aging and cancer.
      A major end product of ROS damage to DNA is the formation of
      apurinic/apyrimidinic (AP) sites, which without removal are known to halt mRNA
      and DNA synthesis, or act as non-coding lesions resulting in the increased
      generation of DNA mutations. In human cells, the major enzyme in correcting the
      deleterious effects of AP sites in DNA is through the participation of AP
      endonuclease (APE), which initiates the removal of baseless sites in DNA through
      the catalytic scission of the phosphodiester bond 5' and adjacent to an AP site.
      Interestingly, APE also possesses an activity (Ref-1) that controls the redox
      status of a number of transcription factors including Fos and Jun. The means by
      which APE/Ref-1 is directed to carry out such disparate roles are unknown. The
      presence of a number of phosphorylation sites scattered throughout both
      functional domains of APE/Ref-1 however offered one possible mechanism that we
      reasoned could play a role in dictating how this protein responds to different
      stimuli. Here we show that the in vitro redox activity of APE/Ref-1 is stimulated
      by PKC phosphorylation. Furthermore, when human cells were exposed to the PKC
      activator phorbol 12-myristate 13-acetate, an increase in redox activity was
      observed that corresponded to an increase in the phosphorylation status of
      APE/Ref-1. Importantly, human cells exposed to the oxidizing agent hypochlorite,
      followed by methyl methanesulfanate, responded with an increase in redox activity
      by APE/Ref-1 that also involved an increase in PKC activity and a corresponding
      increase in the phosphorylation of APE/Ref-1. These results suggest that the
      ability of APE/Ref-1 to perform its in vivo redox function is correlated to its
      susceptibility to PKC phosphorylation that notably occurs in response to DNA
      damaging agents.

PMID- 11452038
TI  - Accessibility of DNA polymerases to repair synthesis during nucleotide excision
      repair in yeast cell-free extracts.
AB  - Nucleotide excision repair (NER) removes a variety of DNA lesions. Using a yeast
      cell-free repair system, we have analyzed the repair synthesis step of NER. NER
      was proficient in yeast mutant cell-free extracts lacking DNA polymerases (Pol)
      beta, zeta or eta. Base excision repair was also proficient without Polbeta.
      Repair synthesis of NER was not affected by thermal inactivation of the
      temperature-sensitive mutant Polalpha (pol1-17), but was reduced after thermal
      inactivation of the temperature-sensitive mutant Poldelta (pol3-1) or
      Polvarepsilon (pol2-18). Residual repair synthesis was observed in pol3-1 and
      pol2-18 mutant extracts, suggesting a repair deficiency rather than a complete
      repair defect. Deficient NER in pol3-1 and pol2-18 mutant extracts was
      specifically complemented by purified yeast Poldelta and Polvarepsilon,
      respectively. Deleting the polymerase catalytic domain of Polvarepsilon (pol2-16)
      also led to a deficient repair synthesis during NER, which was complemented by
      purified yeast Polvarepsilon, but not by purified yeast Poleta. These results
      suggest that efficient repair synthesis of yeast NER requires both Poldelta and
      Polvarepsilon in vitro, and that the low fidelity Poleta is not accessible to
      repair synthesis during NER.

PMID- 11452039
TI  - A homogeneous europium cryptate-based assay for the diagnosis of mutations by
      time-resolved fluorescence resonance energy transfer.
AB  - Oligonucleotide ligation assay (OLA) is considered to be a very useful
      methodology for the detection and characterization of mutations, particularly for
      clinical purposes. The fluorescence resonance energy transfer between a
      fluorescent donor and a suitable fluorophore as acceptor has been applied in the
      past to several scientific fields. This technique is well adapted to nucleic acid
      analysis such as DNA sequencing, DNA hybridization and polymerase chain reaction.
      We describe here a homogeneous format based on the use of a rare earth cryptate
      label as donor: tris-bipyridine-Eu(3+). The long-lived fluorescence of this label
      makes it possible to reach a high sensitivity by using a time-resolved detection
      mode. A non-radiative energy transfer technology, known as time-resolved
      amplification of cryptate emission (TRACE((R))) characterized by a temporal and
      spectral selectivity has been developed. The TRACE((R)) detection of
      characterized single nucleotide polymorphism using the OLA for allelic
      discrimination is proposed. We demonstrate the potentialities of this OLA
      TRACE((R)) methodology through the analysis of K-ras oncogene point mutations.

PMID- 11452040
TI  - Combined SSCP/duplex analysis by capillary electrophoresis for more efficient
      mutation detection.
AB  - SSCP and heteroduplex analysis (HA) continue to be the most popular methods of
      mutation detection due to their simplicity, high sensitivity and low cost. The
      advantages of these methods are most clearly visible when large genes, such as
      BRCA1 and BRCA2, are scanned for scattered unknown mutations and/or when a large
      number of DNA samples is screened for specific mutations. Here we describe a
      novel combined SSCP/duplex analysis adapted to the modern capillary
      electrophoresis (CE) system, which takes advantage of multicolor labeling of DNA
      fragments and laser-induced fluorescence detection. In developing this method, we
      first established the optimum conditions for homoduplex and heteroduplex analysis
      by CE. These were determined based on comprehensive analysis of representative
      Tamra-500 markers and BRCA1 fragments at different concentrations of sieving
      polymer and temperatures in the presence or absence of glycerol. The intrinsic
      features of DNA duplex structures are discussed in detail to explain differences
      in the migration rates between various types of duplexes. When combined
      SSCP/duplex analysis was carried out in single conditions, those found to be
      optimal for analysis of duplexes, all 31 BRCA1 and BRCA2 mutations, polymorphisms
      and variants tested were detected. It is worth noting that the panel of analyzed
      sequence variants was enriched in base substitutions, which are usually more
      difficult to detect. The sensitivity of mutation detection in the SSCP portion
      alone was 90%, and that in the duplex portion was 81% in the single conditions of
      electrophoresis. As is also shown here, the proposed combined SSCP/duplex
      analysis by CE has the potential of being applied to the analysis of pooled
      genomic DNA samples, and to multiplex analysis of amplicons from different gene
      fragments. These modifications may further reduce the costs of analysis, making
      the method attractive for large scale application in SNP scanning and screening.

PMID- 11452042
TI  - Fatal work related injuries in agricultural production and services to
      agriculture sectors of New Zealand, 1985-94.
AB  - OBJECTIVES: To describe work related fatal injuries to agricultural workers in
      New Zealand to identify priority areas for further research and injury control
      measures. METHODS: Injury deaths in New Zealanders aged 15-84 inclusive for the
      period 1985-94 were identified and the coroner's files for these obtained. These
      files were then reviewed to determine whether the death arose as a result of work
      activities. Those deaths considered to be work related were coded for information
      relating to decedent demographics and the circumstances of the fatal injury. Work
      related deaths from injury occurring in the agricultural production and services
      to agriculture sectors were analysed. RESULTS: The rate of fatal injuries to male
      agricultural workers over the study period was 21.2/100 000, with injury deaths
      in the agricultural sectors accounting for nearly a quarter of all work related
      fatal injuries in New Zealand in that time. There was no significant decline in
      fatal injuries to agricultural workers in the study decade. Workers in the 65-84
      age bracket were at substantially higher risk of fatal injury than other age
      groups. Machinery and motor vehicles were commonly associated with fatal injury,
      with overturns on or next to embankments and slopes being the most frequent
      scenario. CONCLUSIONS: The results of this study highlight fatal injuries in
      older workers and machinery incidents (particularly tractors overturning) as
      priority areas for further research into contributing factors and injury control
      measures.

PMID- 11452043
TI  - Respiratory health effects from exposure to carbon black: results of the phase 2
      and 3 cross sectional studies in the European carbon black manufacturing
      industry.
AB  - OBJECTIVES: To assess respiratory morbidity over several cross sectional phases
      in the European carbon black manufacturing industry. METHODS: Participants
      completed an amended (and translated) MRC respiratory morbidity questionnaire
      with additional questions on previous exposures, job history, etc, and spirometry
      traces in each phase. Concurrent with the health outcome measures, personal
      exposure to inhalable dust was measured. RESULTS: Percentage participation rose
      from 90% in phase 2 (19 factories) to 95% in phase 3 (16 factories). Exposure
      dropped slightly between the 2 and 3 phases; as did the prevalence of reporting
      symptoms. Percentage of predicted lung function volumes exceeded 100% for forced
      expired volume in 1 second (FEV(1)) and forced vital capacity (FVC), whereas
      forced mid-expiratory flow (FEF(25%-75%)) and FEV(1)/FVC ratio were below 100% in
      both phases. The multiple linear and logistic regressions showed that carbon
      black had a significant effect on lung function and on most respiratory symptoms,
      respectively. CONCLUSION: Both current and cumulative exposure to carbon black
      have a deleterious effect on respiratory morbidity. Due to the drop in exposure
      between phases 2 and 3, recent exposures seem to have less of an impact on the
      respiratory morbidity in the workers in phase 3 than those in phase 2.

PMID- 11452044
TI  - Particulate matter and daily mortality and hospital admissions in the west
      midlands conurbation of the United Kingdom: associations with fine and coarse
      particles, black smoke and sulphate.
AB  - OBJECTIVES: There is considerable evidence linking ambient particles measured as
      particulate matter with aerodynamic diameter <10 microm (PM(10)) to daily
      mortality and hospital admissions but it is not clear which physical or chemical
      components of the particle mixture are responsible. The relative effects of fine
      particles (PM(2.5)), coarse particles (PM(2.5-10)), black smoke (mainly fine
      particles of primary origin) and sulphate (mainly fine particles of secondary
      origin) were investigated, together with ozone, SO(2), NO(2), and CO, on daily
      mortality and hospital admissions in the west Midlands conurbation of the United
      Kingdom. METHODS: Time series of health outcome and environmental data were
      obtained for the period 1994-6. The relative risk of death or hospital admission
      was estimated with regression techniques, controlling for long term time trends,
      seasonal patterns, influenza epidemics, effects of day of the week, and
      temperature and humidity. Models were adjusted for any remaining residual serial
      correlation and overdispersion. The sensitivities of the estimates for the
      effects of pollution to the inclusion of a second pollutant and seasonal
      interactions (warm or cool) were also examined. RESULTS: Daily all cause
      mortality was not associated with any gaseous or particulate air pollutant in the
      all year analysis, although all measures of particles apart from PM(2.5-10)
      showed significant positive effects of the warm season. Neither respiratory nor
      cardiovascular admissions (all ages) were associated with any air pollutant, and
      there were no important seasonal interactions. However, analysis of admissions by
      age found evidence for various associations-notably between PM(10), PM(2.5),
      black smoke, SO(2,) and ozone (negative) and respiratory admissions in the 0-14
      age group. The coarse fraction, PM(2.5-10) differed from PM(2.5) in having
      smaller and less consistent associations (including several large significant
      negative associations) and a different lag distribution. The results for black
      smoke, an indicator of fine primary carbonaceous particles, were very similar to
      those for PM(2.5), and tended to be more robust in two pollutant models. The
      effects of sulphate, an indicator of secondary particles, also showed some
      similarities to those of PM(2.5). CONCLUSIONS: Clear effects of air pollution on
      mortality and hospital admissions were difficult to discern except in certain age
      or diagnostic subgroups and seasonal analyses. It was also difficult to
      distinguish between different measures of particles. Within these limitations the
      results suggest that the active component of PM(10) resides mostly in the fine
      fraction and that this is due mainly to primary particles from combustion (mainly
      vehicle) sources with a contribution from secondary particles. Effects of the
      coarse fraction cannot be excluded.

PMID- 11452045
TI  - Ultrafine particles and nitrogen oxides generated by gas and electric cooking.
AB  - OBJECTIVES: To measure the concentrations of particles less than 100 nm diameter
      and of oxides of nitrogen generated by cooking with gas and electricity, to
      comment on possible hazards to health in poorly ventilated kitchens. METHODS:
      Experiments with gas and electric rings, grills, and ovens were used to compare
      different cooking procedures. Nitrogen oxides (NO(x)) were measured by a
      chemiluminescent ML9841A NO(x) analyser. A TSI 3934 scanning mobility particle
      sizer was used to measure average number concentration and size distribution of
      aerosols in the size range 10-500 nm. RESULTS: High concentrations of particles
      are generated by gas combustion, by frying, and by cooking of fatty foods.
      Electric rings and grills may also generate particles from their surfaces. In
      experiments where gas burning was the most important source of particles, most
      particles were in the size range 15-40 nm. When bacon was fried on the gas or
      electric rings the particles were of larger diameter, in the size range 50-100
      nm. The smaller particles generated during experiments grew in size with time
      because of coagulation. Substantial concentrations of NO(X) were generated during
      cooking on gas; four rings for 15 minutes produced 5 minute peaks of about 1000
      ppb nitrogen dioxide and about 2000 ppb nitric oxide. CONCLUSIONS: Cooking in a
      poorly ventilated kitchen may give rise to potentially toxic concentrations of
      numbers of particles. Very high concentrations of oxides of nitrogen may also be
      generated by gas cooking, and with no extraction and poor ventilation, may reach
      concentrations at which adverse health effects may be expected. Although
      respiratory effects of exposure to NO(x) might be anticipated, recent
      epidemiology suggests that cardiac effects cannot be excluded, and further
      investigation of this is desirable.

PMID- 11452046
TI  - Exposures and cancer incidence near oil fields in the Amazon basin of Ecuador.
AB  - OBJECTIVES: To examine environmental exposure and incidence and mortality of
      cancer in the village of San Carlos surrounded by oil fields in the Amazon basin
      of Ecuador. METHODS: Water samples of the local streams were analyzed for total
      petroleum hydrocarbons (TPHs). A preliminary list of potential cancer cases from
      1989 to 1998 was prepared. Cases were compared with expected numbers of cancer
      morbidity and mortality registrations from a Quito reference population. RESULTS:
      Water analysis showed severe exposure to TPHs by the residents. Ten patients with
      cancer were diagnosed while resident in the village of San Carlos. An overall
      excess for all types of cancer was found in the male population (8 observed v 3.5
      expected) with a risk 2.26 times higher than expected (95% confidence interval
      (95% CI) 0.97 to 4.46). There was an overall excess of deaths for all types of
      cancer (6 v 1.6 expected) among the male population 3.6 times higher than the
      reference population (95% CI 1.31 to 7.81). CONCLUSIONS: The observed excess of
      cancer might be associated with the pollution of the environment by toxic
      contaminants coming from the oil production.

PMID- 11452047
TI  - Incidence of cancer among bookbinders, printers, photoengravers, and typesetters.
AB  - OBJECTIVES: To to study the risk of cancer, particularly of lung cancer and
      bladder cancer, among workers in the printing industry according to different
      occupations. METHODS: This is a population based retrospective cohort study. The
      cohort comprised 1332 men and 426 women employed in the printing industry in
      Iceland according to a published union registry. A computerised file of the
      cohort was record linked to the Cancer Registry by making use of personal
      identification numbers. Expected numbers of cases of cancer were calculated on
      the basis of number of person-years and specific incidences of cancer sites for
      men and women provided by the Cancer Registry. RESULTS: Among the men (36 217.5
      person-years at risk) there were 125 observed cancers versus 123.66 expected,
      standardised incidence ratio (SIR) 1.01, 95% confidence interval (95% CI) was
      0.84 to 1.20. The SIR (95% CI) for liver cancer was 1.97 (0.55 to 5.20) and the
      SIR for non-Hodgkin's lymphoma was 2.26 (0.96 to 4.41). No excess risk for cancer
      was found among women (8631.0 person-years at risk). The SIR (95% CI) for liver
      cancer was 4.21 (0.47 to 15.20) and for non-Hodgkin's lymphoma it was 4.99 (1.61
      to 11.63) among the typesetters. A survey on smoking habits among active and
      retired union members showed that they smoked less than a random sample of the
      general population. CONCLUSION: The cancer site most often reported to show
      excess risk among printing industry workers has been the lung and the urinary
      bladder; however, this was not found in the present study. This may be explained
      by difference in smoking habits among union members compared with the general
      population. There is a high occurrence of non-Hodgkin's lymphoma, particularly
      among typesetters, which warrants further studies.

PMID- 11452048
TI  - A prospective study of work related factors and physical exercise as predictors
      of shoulder pain.
AB  - OBJECTIVES: To evaluate the effects of work related and individual factors as
      well as physical activity and sports on the incidence and persistence of shoulder
      pain among forestry workers. METHODS: Workers in a large Finnish forestry company
      replied to a questionnaire (a modified version of the Nordic questionnaire) on
      musculoskeletal pain and its possible risk factors for 4 consecutive years 1992
      5. This 1 year follow up study covers the time 1994-5. Year 1994 was chosen as
      baseline because in that year the questionnaire contained for the first time more
      detailed questions about different sports. The response rate in 1995 was 90%. The
      effects of the predictors on 1 year incidence and persistence of shoulder pain
      were studied with multivariate logistic regression modelling. RESULTS: At
      baseline, 2094 subjects had been free of shoulder pain during the preceding 12
      months. After 1 year, 14% (n=285) reported having mild or severe shoulder pain.
      Higher age, obesity, and mental stress as well as physically strenuous work and
      working with trunk forward flexed or with a hand above shoulder level increased
      the risk of incident shoulder pain. Of the different sports activities, dancing
      increased the risk of incident pain whereas jogging decreased the risk
      significantly. Of those 419 workers who had severe shoulder pain at baseline, 55%
      (n=230) still had severe pain 1 year later. Higher age, overload at work, and
      working with a hand above shoulder level increased the risk of persistent severe
      shoulder pain whereas cross country skiing and general sports activity decreased
      the risk. CONCLUSION: Our results support the current view that shoulder pain is
      the result of many factors, including occupational and individual factors. In
      this longitudinal study, physical work with a heavy load, awkward work postures,
      mental stress, and obesity were the risk factors at which preventive measures
      could be aimed. As a new finding, physical exercise had more protective than
      impairing effects on the shoulders.

PMID- 11452049
TI  - Primary infertility in nuclear industry employees: report from the nuclear
      industry family study.
AB  - OBJECTIVE: To determine whether men and women who are occupationally exposed to
      ionising radiation are at increased risk of primary infertility. METHODS: A cross
      sectional analysis of reproductive outcome was reported in an occupational cohort
      of nuclear industry workers from the Atomic Energy Authority, Atomic Weapons
      Establishment, and British Nuclear Fuels in the United Kingdom. Data on
      employment and radiation monitoring supplied by employers were linked to data
      obtained from self administered questionnaires sent to all current employees and
      a sample of past workers. A total of 5353 men and 603 women aged 40 years or more
      at the time of survey whose first pregnancy, or attempt at pregnancy, had
      occurred after first employment in the nuclear industry were recruited to the
      study. Primary infertility was defined as consultation with a doctor about the
      failure to achieve at least one viable (24 weeks gestational age or more)
      pregnancy. RESULTS: 2.6% Of men and 3.7% of women reported primary infertility.
      For men, this proportion did not differ by amount of radiation monitored or by
      dose received. The prevalence of infertility was higher among monitored women
      than non-monitored women, but not significantly so and the numbers were too small
      to draw any firm conclusions. CONCLUSIONS: No support was found for a hypothesis
      linking exposure to low level ionising radiation among men with primary
      infertility. There was weak evidence of an association in women, but the
      relatively few monitored women prevented detailed examination of these data.

PMID- 11452050
TI  - Sex ratio in offspring of those affected by dioxin and dioxin-like compounds: the
      Yusho, Seveso, and Yucheng incidents.
AB  - Sex ratios in the offspring of those affected by dioxins or dioxin-like compounds
      have been reported from Seveso, Italy and Yucheng, Taiwan. The sex ratio of live
      births in Yusho, Japan after a similar accidental massive exposure to
      polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in
      1968 are reviewed. Data on all births among parents exposed to the compounds from
      1968 to 1977 in Fukuoka and a region of Nagasaki, the two areas affected, are
      reported. In total there were 85 live births in those regions. The sex ratio was
      not significantly different from normal (0.513). To evaluate hormonal disrupting
      activity or effects on reproductive outcome by PCBs and PCDFs, a further
      investigation of sex in offspring of the Yusho victims, especially offspring of
      those who were younger than 19 years of age at the time of the Yusho incident, is
      needed.

PMID- 11452051
TI  - Nasal, eye, and skin irritation in dockyard painters.
AB  - OBJECTIVES: To determine whether the risk of irritant symptoms in painters is
      related to their exposure to paint. METHODS: The prevalences of skin, eye and
      nasal symptoms were compared in 260 United Kingdom and 109 Chinese dockyard
      painters, 539 British community controls, and 255 Chinese dockyard controls,
      relative to their exposure to paints. RESULTS: Painters showed an excess of
      irritant symptoms compared with controls. Adjusted relative risks (RRs) (95%
      confidence interval (95% CI) were: for skin irritation 1.58 (1.19 to 2.08) in
      British painters and 2.68 (1.73 to 4.09) in Chinese painters; for eye irritation,
      1.41 (0.98 to 2.05) and 3.01 (1.90 to 4.76); and for nasal irritation, 1.53 (1.10
      to 2.14) and 6.73 (3.53 to 12.82), respectively. Exposure duration-response
      relations were found for these symptoms; the risks decreased with time after
      exposure ended. CONCLUSIONS: Irritant symptoms occur more often in dockyard
      painters than in controls, and this is likely to be a response to exposure to
      paint.

PMID- 11452052
TI  - Glutaraldehyde induced asthma in endoscopy nursing staff.

PMID- 11452053
TI  - Aging workers.

PMID- 11452054
TI  - Intravenous urography: technique and interpretation.

PMID- 11452056
TI  - Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic
      findings.
AB  - Aspergillosis is a serious pathologic condition caused by Aspergillus organisms
      and is frequently seen in immunocompromised patients. At computed tomography
      (CT), saprophytic aspergillosis (aspergilloma) is characterized by a mass with
      soft-tissue attenuation within a lung cavity. The mass is typically separated
      from the cavity wall by an airspace ("air crescent" sign) and is often associated
      with thickening of the wall and adjacent pleura. CT findings in allergic
      bronchopulmonary aspergillosis consist primarily of mucoid impaction and
      bronchiectasis involving predominantly the segmental and subsegmental bronchi of
      the upper lobes. Aspergillus necrotizing bronchitis may manifest as an
      endobronchial mass, obstructive pneumonitis or collapse, or a hilar mass.
      Bronchiolitis is characterized by centrilobular nodules and branching linear or
      nodular areas of increased attenuation ("tree-in-bud" pattern). Obstructing
      bronchopulmonary aspergillosis mimics allergic bronchopulmonary aspergillosis at
      CT and manifests as bilateral bronchial and bronchiolar dilatation, large mucoid
      impactions, and diffuse lower lobe consolidation caused by postobstructive
      atelectasis. Characteristic CT findings in angioinvasive aspergillosis consist of
      nodules surrounded by a halo of ground-glass attenuation ("halo sign") or pleura
      based, wedge-shaped areas of consolidation. Although imaging findings in
      pulmonary aspergillosis may be nonspecific, in the appropriate clinical setting,
      familiarity with the CT findings may suggest or even help establish the
      diagnosis.

PMID- 11452057
TI  - Thoracic sequelae and complications of tuberculosis.
AB  - Pulmonary tuberculosis is caused by Mycobacterium tuberculosis when droplet
      nuclei laden with bacilli are inhaled. In accordance with the virulence of the
      organism and the defenses of the host, tuberculosis can occur in the lungs and in
      extrapulmonary organs. A variety of sequelae and complications can occur in the
      pulmonary and extrapulmonary portions of the thorax in treated or untreated
      patients. These can be categorized as follows: (a) parenchymal lesions, which
      include tuberculoma, thin-walled cavity, cicatrization, end-stage lung
      destruction, aspergilloma, and bronchogenic carcinoma; (b) airway lesions, which
      include bronchiectasis, tracheobronchial stenosis, and broncholithiasis; (c)
      vascular lesions, which include pulmonary or bronchial arteritis and thrombosis,
      bronchial artery dilatation, and Rasmussen aneurysm; (d) mediastinal lesions,
      which include lymph node calcification and extranodal extension,
      esophagomediastinal or esophagobronchial fistula, constrictive pericarditis, and
      fibrosing mediastinitis; (e) pleural lesions, which include chronic empyema,
      fibrothorax, bronchopleural fistula, and pneumothorax; and (f) chest wall
      lesions, which include rib tuberculosis, tuberculous spondylitis, and malignancy
      associated with chronic empyema. These varieties of radiologic manifestations can
      mimic other disease entities. Therefore, recognition and understanding of the
      radiologic manifestations of the thoracic sequelae and complications of
      tuberculosis are important to facilitate diagnosis.

PMID- 11452059
TI  - Radiographic and CT appearances of the major fissures.
AB  - The major fissure is an important anatomic landmark in the interpretation of
      chest radiographs and computed tomographic (CT) scans. At radiography, the major
      fissures normally appear as hairlines of soft-tissue density; at conventional CT,
      they typically appear as lucent, hypovascular bands; and at high-resolution CT,
      they most often appear as sharp lines. The superolateral major fissure usually
      manifests as a curving edge at the upper lateral lung field with lateral opacity
      and medial lucency. The vertical fissure line appears as a fine, linear shadow,
      commencing in or near the costophrenic angle and coursing upward. The
      superomedial major fissure manifests as a short, obliquely oriented straight
      line. Progressive widening of the major fissure inferiorly manifests as a
      triangular area of increased opacity and represents intrafissural fat. Various
      inflammatory, granulomatous, neoplastic, and abnormal hemodynamic conditions
      involving the major fissure can affect its imaging appearance. Oblique
      orientation of the major fissure may complicate radiographic interpretation. The
      fissure may be incomplete or absent, complicating identification of various
      diseases. An incomplete major fissure may lead to disease spread, collateral air
      drift, or the "incomplete fissure sign," a sign that may, however, also be
      present in cases of complete fissure. Knowledge of the anatomy and normal
      variants of the major fissures is essential for recognizing their variable
      imaging appearances as well as related abnormalities.

PMID- 11452060
TI  - Interpretation of transient hepatic attenuation differences in dynamic CT.

PMID- 11452062
TI  - Hepatic adenomas: imaging and pathologic findings.
AB  - Hepatocellular adenoma is a rare benign lesion that is most often seen in young
      women with a history of oral contraceptive use. It is typically solitary,
      although multiple lesions have been reported, particularly in patients with
      glycogen storage disease and liver adenomatosis. Because of the risk of
      hemorrhage and malignant transformation, hepatocellular adenomas must be
      identified and treated promptly. At pathologic analysis, hepatocellular adenoma
      is usually a well-circumscribed, nonlobulated lesion, and at gross examination,
      resected adenomas frequently demonstrate areas of hemorrhage and infarction. Most
      adenomas are not specifically diagnosed at ultrasonography (US) and are usually
      further evaluated with computed tomography (CT) or other imaging modalities.
      Color Doppler US may help differentiate hepatocellular adenoma from focal nodular
      hyperplasia. Multiphasic helical CT allows more accurate detection and
      characterization of focal hepatic lesions. Hepatocellular adenomas are typically
      bright on T1-weighted magnetic resonance images and predominantly hyperintense
      relative to liver on T2-weighted images. The prognosis of hepatic adenoma is not
      well established. Criteria that guide treatment include the number and size of
      the lesions, the presence of symptoms, and the surgical risk incurred by the
      patient. Understanding the imaging appearance of hepatocellular adenoma can help
      avoid misdiagnosis and facilitate prompt, effective treatment.

PMID- 11452064
TI  - Cystic focal liver lesions in the adult: differential CT and MR imaging features.
AB  - Cystic lesions of the liver in the adult can be classified as developmental,
      neoplastic, inflammatory, or miscellaneous. Although in some cases it is
      difficult to distinguish these entities with imaging criteria alone, certain
      cystic focal liver lesions have classic computed tomographic (CT) and magnetic
      resonance (MR) imaging features, which are important for the radiologist to
      understand and recognize. Lesions with such features include simple (bile duct)
      cyst, autosomal dominant polycystic liver disease, biliary hamartoma, Caroli
      disease, undifferentiated (embryonal) sarcoma, biliary cystadenoma and
      cystadenocarcinoma, cystic subtypes of primary liver neoplasms, cystic
      metastases, pyogenic and amebic abscesses, intrahepatic hydatid cyst,
      extrapancreatic pseudocyst, and intrahepatic hematoma and biloma. Specific CT and
      MR imaging findings that are important to recognize are the size of the lesion;
      the presence and thickness of a wall; the presence of septa, calcifications, or
      internal nodules; the enhancement pattern; the MR cholangiographic appearance;
      and the signal intensity spectrum. In addition, access to critical clinical
      information remains extremely important. The most important clinical parameters
      defined include age and gender, clinical history, and symptoms. An understanding
      of the classic CT and MR imaging appearances of cystic focal liver lesions will
      allow more definitive diagnosis and shorten the diagnostic work-up.

PMID- 11452065
TI  - Radiologic findings of Behcet syndrome involving the gastrointestinal tract.
AB  - Behcet syndrome is characterized by the histopathologic finding of nonspecific
      vasculitis in multiple organs. The diagnosis is usually made on the basis of the
      combination of clinical signs and symptoms. This disease involves the
      gastrointestinal tract in 10%-50% of patients, and the terminal ileum and cecum
      are chiefly affected. Barium study is useful in demonstrating the characteristic
      radiographic features of Behcet syndrome involving the gastrointestinal tract.
      The presence of deep, penetrating ulcers results in a high rate of complications,
      such as perforation, fistula, hemorrhage, and peritonitis. Furthermore,
      recurrence of disease adjacent to or at the surgical anastomosis is common.
      Computed tomography is useful in determining the extent of the lesions and in
      identifying cases in which complications are likely to occur. Familiarity with
      the various radiologic findings of Behcet syndrome involving the gastrointestinal
      tract helps in making an early diagnosis, as well as in establishing an
      appropriate treatment strategy.

PMID- 11452067
TI  - Imaging-guided injection techniques with fluoroscopy and CT for spinal pain
      management.
AB  - Local spinal pain and radiculopathy are common conditions that debilitate
      millions of Americans annually. Most cases are successfully treated
      conservatively with rest or physical therapy. Chiropractic manipulation or, in
      some cases, surgery may also be performed. Percutaneous injection has been used
      for spinal pain management for many years, but many of these procedures have
      historically been performed without imaging guidance. Recently, however, newer
      minimally invasive, imaging-guided percutaneous techniques have been added to the
      list of available treatment options for spinal pain. Imaging-guided techniques
      with fluoroscopy or computed tomography increase the precision of these
      procedures and help confirm needle placement. Cervical, thoracic, lumbosacral,
      and sacroiliac pain can be evaluated and treated safely and effectively with
      injections of local anesthetics or long-acting steroids into facet joints,
      sacroiliac joints, selective nerve roots, spondylolytic areas, and the epidural
      space. Because imaging-guided techniques appear to provide better results and
      reduce complication rates, they are becoming more popular despite controversy
      regarding their effectiveness. Controversy will continue to surround these
      imaging-guided techniques until large, double-blinded studies become available.
      In the meantime, there is an increased demand for these procedures from referring
      physicians, and it is important to be able to safely perform them with a minimum
      of patient discomfort.

PMID- 11452069
TI  - A new view of the neonatal brain: clinical utility of supplemental neurologic US
      imaging windows.
AB  - Anterior fontanelle imaging has traditionally been the mainstay of neonatal
      cranial ultrasonography (US). However, this traditional approach has limited
      diagnostic accuracy, which has led to increasing use of two alternate neurologic
      US imaging techniques: posterior fontanelle imaging and mastoid fontanelle
      imaging. These alternate techniques can help detect pathologic conditions and
      structural malformations in the neonatal brain. Posterior fontanelle imaging
      allows improved detection of intraventricular hemorrhage. This technique better
      demonstrates subtle differences in echogenicity between clot and a choroid glomus
      and depicts clot extending into the occipital and temporal horns. Mastoid
      fontanelle imaging is particularly useful in detecting hemorrhage involving the
      brainstem, cerebellum, and subarachnoid cisterns. It greatly facilitates clot
      detection in the fourth ventricle and cisterna magna because the tissues
      surrounding these structures are normally echogenic. Mastoid fontanelle imaging
      can also help distinguish holoprosencephaly from aqueductal stenosis and identify
      small malformations of the posterior fossa. Color Doppler US may help identify
      normal variants such as calcar avis and lobular choroid plexus, and adjunct
      magnetic resonance imaging can help distinguish normal structures from a true
      Dandy-Walker variant. Use of posterior fontanelle imaging and mastoid fontanelle
      imaging can significantly augment the diagnostic power of neurologic US.

PMID- 11452070
TI  - Scintigraphic features of autoimmune thyroiditis.
AB  - The term autoimmune thyroiditis encompasses multiple inflammatory conditions of
      the thyroid gland, each with variable clinical manifestations. The more acute
      forms, silent (painless) thyroiditis and postpartum thyroiditis, are associated
      with transient hyperthyroidism and are sometimes mistaken for Graves disease. The
      chronic form, Hashimoto thyroiditis (chronic autoimmune thyroiditis), results in
      goiter and eventual hypothyroidism unless it is recognized and treated promptly.
      Thyroid uptake measurements and scintigraphic findings (usually obtained with
      technetium-99m or iodine-123) play a complementary role along with thyroid
      function testing in differentiating autoimmune thyroiditis from other thyroid
      diseases, thereby influencing treatment. In some cases, histologic evaluation of
      biopsy specimens is required to yield the definitive diagnosis. Knowledge of the
      entire spectrum of these disorders is essential for appropriate case management.

PMID- 11452071
TI  - Mucinous colloid adenocarcinoma of the urachus.

PMID- 11452073
TI  - Sickle cell anemia.
AB  - Sickle cell anemia (SCA) is a disease caused by production of abnormal
      hemoglobin, which binds with other abnormal hemoglobin molecules within the red
      blood cell to cause rigid deformation of the cell. This deformation impairs the
      ability of the cell to pass through small vascular channels; sludging and
      congestion of vascular beds may result, followed by tissue ischemia and
      infarction. Infarction is common throughout the body in the patient with SCA, and
      it is responsible for the earliest clinical manifestation, the acute pain crisis,
      which is thought to result from marrow infarction. Over time, such insults result
      in medullary bone infarcts and epiphyseal osteonecrosis. In the brain, white
      matter and gray matter infarcts are seen, causing cognitive impairment and
      functional neurologic deficits. The lungs are also commonly affected, with
      infarcts, emboli (from marrow infarcts and fat necrosis), and a markedly
      increased propensity for pneumonia. The liver, spleen, and kidney may experience
      infarction as well. An unusual but life-threatening complication of SCA is
      sequestration syndrome, wherein a considerable amount of the intravascular volume
      is sequestered in an organ (usually the spleen), causing vascular collapse; its
      pathogenesis is unknown. Finally, because the red blood cells are abnormal, they
      are removed from the circulation, resulting in a hemolytic anemia. For the
      patient with SCA, however, the ischemic complications of the disease far outweigh
      the anemia in clinical importance.

PMID- 11452074
TI  - State-of-the-art adrenal imaging.
AB  - The adrenal gland is a common site of disease, and detection of adrenal masses
      has increased with the expanding use of cross-sectional imaging. Radiology is
      playing a critical role in not only the detection of adrenal abnormalities but in
      characterizing them as benign or malignant. The purpose of the article is to
      illustrate and describe the appropriate radiologic work-up for diseases affecting
      the adrenal gland. The work-up of a suspected hyperfunctioning adrenal mass
      (pheochromocytoma and aldosteronoma) should start with appropriate biochemical
      screening tests followed by thin-collimation computed tomography (CT). If results
      of CT are not diagnostic, magnetic resonance (MR) and nuclear medicine imaging
      examinations should be performed. CT has become the study of choice to
      differentiate a benign adenoma from a metastasis in the oncology patient. If the
      attenuation of the adrenal gland is over 10 HU at nonenhanced CT, contrast
      material-enhanced CT should be performed and washout calculated. Over 50% washout
      of contrast material on a 10-minute delayed CT scan is diagnostic of an adenoma.
      For adrenal lesions that are indeterminate at CT in the oncology patient,
      chemical shift MR imaging or adrenal biopsy should be performed. Certain features
      can be used by the radiologist to establish a definitive diagnosis for most
      adrenal masses (including carcinoma, infections, and hemorrhage) based on imaging
      findings alone.

PMID- 11452075
TI  - Challenges and opportunities for radiology in the next millennium: re-engineering
      the radiology practice in an electronic world.

PMID- 11452076
TI  - Computerized physician order entry and decision support: improving the quality of
      care.

PMID- 11452077
TI  - Value innovation in the radiology practice.

PMID- 11452078
TI  - Do computers teach better? A media comparison study for case-based teaching in
      radiology.
AB  - A prospective study was performed to better define the role of computers in
      teaching radiology to medical students. Two hundred twenty-five 3rd-year students
      were randomly assigned to one of four groups and exposed to 10 radiology cases as
      well as to a voluntary weekly radiology lecture. Group A used computer-based
      cases with interactive elements; group B used computer-based cases without
      interactive elements; group C used paper-based cases with interactive elements;
      and group D was not exposed to the cases and served as a control group. On a
      multiple-choice question test, groups A, B, and C showed significant improvement
      (+11.2%, +15.1%, and +13.0%, respectively), whereas group D did not (+0.6%). On
      an image interpretation test, group A showed the most improvement (+15.7% [P
      <.001]), followed by group B (+15.1% [P <.01]) and group C (+10.2% [P <.05]);
      group D showed no significant improvement (+8.5%). No significant differences in
      the learning outcome were found between the two interactive groups (computer
      based and paper based). Computer-based teaching with case studies (with or
      without interactivity) improves students' problem-solving ability in radiology.

PMID- 11452079
TI  - Fluoroscopy: patient radiation exposure issues.
AB  - Fluoroscopic procedures (particularly prolonged interventional procedures) may
      involve high patient radiation doses. The radiation dose depends on the type of
      examination, the patient size, the equipment, the technique, and many other
      factors. The performance of the fluoroscopy system with respect to radiation dose
      is best characterized by the receptor entrance exposure and skin entrance
      exposure rates, which should be assessed at regular intervals. Management of
      patient exposure involves not only measurement of these rates but also clinical
      monitoring of patient doses. Direct monitoring of patient skin doses during
      procedures is highly desirable, but current methods still have serious
      limitations. Skin doses may be reduced by using intermittent exposures, grid
      removal, last image hold, dose spreading, beam filtration, pulsed fluoroscopy,
      and other dose reduction techniques. Proper training of fluoroscopic operators,
      understanding the factors that influence radiation dose, and use of various dose
      reduction techniques may allow effective management of patient dose.

PMID- 11452080
TI  - Advanced cardiac MR imaging of ischemic heart disease.
AB  - Important advances in rapid magnetic resonance (MR) imaging technology and its
      application to cardiovascular imaging have been made during the past decade. High
      field-strength clinical magnets, high-performance gradient hardware, and
      ultrafast pulse sequence technology are rapidly making the vision of a
      comprehensive "one-stop shop" cardiac MR imaging examination a reality. This
      examination is poised to have a significant effect on the management of coronary
      artery disease by means of assessment of wall motion with tagging and
      pharmacologic stress testing, evaluation of the coronary microvasculature with
      perfusion imaging, and direct visualization of the coronary arteries with MR
      coronary angiography. This article reviews current state-of-the-art pulse
      sequence technology and its application to the evaluation of ischemic heart
      disease by means of MR tagging with dobutamine stress testing, MR perfusion
      imaging, and MR coronary angiography. Cutting edge areas of research in coil
      design and exciting new areas of metabolic and oxygen level-dependent imaging are
      also explored.

PMID- 11452081
TI  - Haplotype variation and linkage disequilibrium in 313 human genes.
AB  - Variation within genes has important implications for all biological traits. We
      identified 3899 single nucleotide polymorphisms (SNPs) that were present within
      313 genes from 82 unrelated individuals of diverse ancestry, and we organized the
      SNPs into 4304 different haplotypes. Each gene had several variable SNPs and
      haplotypes that were present in all populations, as well as a number that were
      population-specific. Pairs of SNPs exhibited variability in the degree of linkage
      disequilibrium that was a function of their location within a gene, distance from
      each other, population distribution, and population frequency. Haplotypes
      generally had more information content (heterozygosity) than did individual SNPs.
      Our analysis of the pattern of variation strongly supports the recent expansion
      of the human population.

PMID- 11452082
TI  - An optical clock based on a single trapped 199Hg+ ion.
AB  - Microwave atomic clocks have been the de facto standards for precision time and
      frequency metrology over the past 50 years, finding widespread use in basic
      scientific studies, communications, and navigation. However, with its higher
      operating frequency, an atomic clock based on an optical transition can be much
      more stable. We demonstrate an all-optical atomic clock referenced to the 1.064
      petahertz transition of a single trapped 199Hg+ ion. A clockwork based on a mode
      locked femtosecond laser provides output pulses at a 1-gigahertz rate that are
      phase-coherently locked to the optical frequency. By comparison to a laser-cooled
      calcium optical standard, an upper limit for the fractional frequency instability
      of 7 x 10(-15) is measured in 1 second of averaging-a value substantially better
      than that of the world's best microwave atomic clocks.

PMID- 11452083
TI  - A cellular function for the RNA-interference enzyme Dicer in the maturation of
      the let-7 small temporal RNA.
AB  - The 21-nucleotide small temporal RNA (stRNA) let-7 regulates developmental timing
      in Caenorhabditis elegans and probably in other bilateral animals. We present in
      vivo and in vitro evidence that in Drosophila melanogaster a developmentally
      regulated precursor RNA is cleaved by an RNA interference-like mechanism to
      produce mature let-7 stRNA. Targeted destruction in cultured human cells of the
      messenger RNA encoding the enzyme Dicer, which acts in the RNA interference
      pathway, leads to accumulation of the let-7 precursor. Thus, the RNA interference
      and stRNA pathways intersect. Both pathways require the RNA-processing enzyme
      Dicer to produce the active small-RNA component that represses gene expression.

PMID- 11452085
TI  - Unification for European immunology?

PMID- 11452084
TI  - Crystal structure of sensory rhodopsin II at 2.4 angstroms: insights into color
      tuning and transducer interaction.
AB  - We report an atomic-resolution structure for a sensory member of the microbial
      rhodopsin family, the phototaxis receptor sensory rhodopsin II (NpSRII), which
      mediates blue-light avoidance by the haloarchaeon Natronobacterium pharaonis. The
      2.4 angstrom structure reveals features responsible for the 70- to 80-nanometer
      blue shift of its absorption maximum relative to those of haloarchaeal transport
      rhodopsins, as well as structural differences due to its sensory, as opposed to
      transport, function. Multiple factors appear to account for the spectral tuning
      difference with respect to bacteriorhodopsin: (i) repositioning of the
      guanidinium group of arginine 72, a residue that interacts with the counterion to
      the retinylidene protonated Schiff base; (ii) rearrangement of the protein near
      the retinal ring; and (iii) changes in tilt and slant of the retinal polyene
      chain. Inspection of the surface topography reveals an exposed polar residue,
      tyrosine 199, not present in bacteriorhodopsin, in the middle of the membrane
      bilayer. We propose that this residue interacts with the adjacent helices of the
      cognate NpSRII transducer NpHtrII.

PMID- 11452086
TI  - Embryonic stem cells. Rumors and trial balloons precede Bush's funding decision.

PMID- 11452087
TI  - Ph.D. training. Spain cuts off aid to foreign Ph.D. students.

PMID- 11452088
TI  - Human evolution. Another emissary from the dawn of humanity.

PMID- 11452089
TI  - Scientific publishing. Journals offered free to poorest nations.

PMID- 11452090
TI  - Cell biology. Fresh molecule whets appetite.

PMID- 11452091
TI  - Virology. New finding heats up the hot zone.

PMID- 11452092
TI  - Cassini-Huygens. Mission to Saturn rises from ashes.

PMID- 11452093
TI  - Undergraduate research. Liberal arts schools pass science checkup.

PMID- 11452094
TI  - Smithsonian Institution. Turmoil behind the exhibits.

PMID- 11452095
TI  - Jewels in the crown I. Astrophysical observatory.

PMID- 11452096
TI  - Jewels in the crown II. Environment center.

PMID- 11452097
TI  - Jewels in the crown III. Tropical research center.

PMID- 11452098
TI  - Climate change. Major challenges for Bush's climate initiative.

PMID- 11452099
TI  - Climate change. Scientists shower climate change delegates with paper.

PMID- 11452100
TI  - Supercomputing. High-powered GRAPEs take on the cosmos.

PMID- 11452101
TI  - Intellectual property. Patents, secrecy, and DNA.

PMID- 11452102
TI  - Superconductivity. Super boron.

PMID- 11452103
TI  - Neuroscience. Parkin and its substrates.

PMID- 11452104
TI  - Atmospheric science. The mass-independent ozone isotope effect.

PMID- 11452105
TI  - Cancer. What does radiotherapy do to endothelial cells?

PMID- 11452106
TI  - Immunology. Tampering with the immune system.

PMID- 11452107
TI  - Immune control, memory, and vaccines.

PMID- 11452108
TI  - Driving a stake into resurgent TB.

PMID- 11452109
TI  - 'Breeding' antigens for new vaccines.

PMID- 11452110
TI  - How DNA shuffling works.

PMID- 11452111
TI  - Closing of Basel institute scatters immunologists.

PMID- 11452112
TI  - The art of the probable: system control in the adaptive immune system.
AB  - The immune system provides very effective host defense against infectious agents.
      Although many details are known about the cells and molecules involved, a broader
      "systems engineering" view of this complex system is just beginning to emerge.
      Here the argument is put forward that stochastic events, potent amplification
      mechanisms, feedback controls, and heterogeneity arising from spatially dispersed
      cell interactions give rise to many of the gross properties of the immune system.
      A better appreciation of these underlying features will not only add to our basic
      understanding of how immunity develops or goes awry, but also illuminate new
      directions for manipulating the system in prophylactic and therapeutic settings.

PMID- 11452113
TI  - T cell death and memory.
AB  - In typical immune responses, contact with antigen causes naive T cells to
      proliferate and differentiate into effector cells. After the pathogen is
      destroyed, most effector T cells are eliminated-thereby preserving the primary T
      cell repertoire-but some cells survive and form long-lived memory cells. During
      each stage of this process, the life or death fate of T cells is strictly
      regulated.

PMID- 11452114
TI  - Arrested differentiation, the self-renewing memory lymphocyte, and vaccination.
AB  - Vaccination for persistent viral or bacterial infections must program the immune
      system for a lifelong need to generate antigen-specific effector lymphocytes. How
      the immune system does this is not known, but recent studies have shown that a
      subset of B lymphocytes, the germinal center B cell, is capable of self-renewal
      because it expresses a transcriptional repressor, BCL6, that blocks terminal
      differentiation. If a similar mechanism for arresting differentiation exists for
      long-lived, antigen-selected lymphocytes, a stem cell-like capacity for self
      renewal could be the basis for the continual generation of effector lymphocytes
      from the memory pool. Understanding how to regulate the terminal differentiation
      of lymphocytes will improve immunotherapeutic approaches for chronic infectious
      diseases and cancer.

PMID- 11452115
TI  - Regulation of the immune response by antigen.
AB  - How, why, and when specific T and B lymphocytes respond against infection follow
      explicit rules, but how this can be assessed experimentally depends crucially on
      the methodology used. In this Viewpoint, we discuss the parameters of receptor
      specificity and antigen that determine whether an immune response can be
      accurately measured against model antigens and how this relates to protection
      against a given pathogen. We suggest that antigen structure, localization, dose,
      and time during which antigen is available are all decisive factors in regulating
      an immune response.

PMID- 11452116
TI  - Sensing pathogens and tuning immune responses.
AB  - The immune system is capable of making qualitatively distinct responses against
      different microbial infections, and recent advances are starting to reveal how it
      manages this complex task. An integral component of the immune system is a
      network of cells known as dendritic cells (DCs), which sense different microbial
      stimuli and convey this information to lymphocytes. A better understanding of DC
      biology has allowed a model to be constructed in which the type of immune
      response to an infection is viewed as a function of several determinants,
      including the subpopulation of DCs, the nature of the microbe, microbe
      recognition receptors, and the cytokine microenvironment.

PMID- 11452117
TI  - Visible-light photocatalysis in nitrogen-doped titanium oxides.
AB  - To use solar irradiation or interior lighting efficiently, we sought a
      photocatalyst with high reactivity under visible light. Films and powders of
      TiO(2-x)N(x) have revealed an improvement over titanium dioxide (TiO2) under
      visible light (wavelength < 500 nanometers) in optical absorption and
      photocatalytic activity such as photodegradations of methylene blue and gaseous
      acetaldehyde and hydrophilicity of the film surface. Nitrogen doped into
      substitutional sites of TiO2 has proven to be indispensable for band-gap
      narrowing and photocatalytic activity, as assessed by first-principles
      calculations and x-ray photoemission spectroscopy.

PMID- 11452118
TI  - Superconductivity in boron.
AB  - Metals formed from light elements are predicted to exhibit intriguing states of
      electronic order. Of these materials, those containing boron are of considerable
      current interest because of their relatively high superconducting temperatures.
      We have investigated elemental boron to very high pressure using diamond anvil
      cell electrical conductivity techniques. We find that boron transforms from a
      nonmetal to a superconductor at about 160 gigapascals (GPa). The critical
      temperature of the transition increases from 6 kelvin (K) at 175 GPa to 11.2 K at
      250 GPa, giving a positive pressure derivative of 0.05 K/GPa. Although the
      observed metallization pressure is compatible with the predictions of first
      principles calculations, superconductivity in boron remains to be explored
      theoretically. The present results constitute a record pressure for both
      electrical conductivity studies and investigations of superconductivity in dense
      matter.

PMID- 11452119
TI  - Melt production beneath Mt. Shasta from boron data in primitive melt inclusions.
AB  - Most arc magmas are thought to be generated by partial melting of the mantle
      wedge induced by infiltration of slab-derived fluids. However, partial melting of
      subducting oceanic crust has also been proposed to contribute to the melt
      generation process, especially when young and hot lithosphere is being subducted.
      The isotopic composition of boron measured in situ in olivine-hosted primitive
      melt inclusions in a basaltic andesite from Mt. Shasta, California, is
      characterized by large negative values that are also highly variable (delta(11)B
      = -21.3 to -0.9 per mil). The boron concentrations, from 0.7 to 1.6 parts per
      million, are lower than in most other arc lavas. The relation between
      concentration and isotopic composition of boron observed here supports a
      hypothesis that materials left after dehydration of the subducting slab may have
      contributed to the generation of basaltic andesite lavas at Mt. Shasta.

PMID- 11452120
TI  - Freshwater forcing of abrupt climate change during the last glaciation.
AB  - Large millennial-scale fluctuations of the southern margin of the North American
      Laurentide Ice Sheet occurred during the last deglaciation, when the margin was
      located between about 43 degrees and 49 degrees N. Fluctuations of the ice margin
      triggered episodic increases in the flux of freshwater to the North Atlantic by
      rerouting continental runoff from the Mississippi River drainage to the Hudson or
      St. Lawrence Rivers. We found that periods of increased freshwater flow to the
      North Atlantic occurred at the same time as reductions in the formation of North
      Atlantic Deep Water, thus providing a mechanism for observed climate variability
      that may be generally characteristic of times of intermediate global ice volume.

PMID- 11452121
TI  - Developmental changes due to long-distance movement of a homeobox fusion
      transcript in tomato.
AB  - Long-distance movement of RNA through the phloem is known to occur, but the
      functional importance of these transported RNAs has remained unclear. Grafting
      experiments with a naturally occurring dominant gain-of-function leaf mutation in
      tomato were used to demonstrate long-distance movement of mutant messenger RNA
      (mRNA) into wild-type scions. The stock-specific pattern of mRNA expression was
      graft transmissible, indicating that the mRNA accumulation pattern is inherent to
      the transcript and not attributable to the promoter. The translocated mRNA caused
      changes in leaf morphology of the wild-type scions, suggesting that the
      translocated RNA is functional.

PMID- 11452122
TI  - Production of polyunsaturated fatty acids by polyketide synthases in both
      prokaryotes and eukaryotes.
AB  - Polyunsaturated fatty acids (PUFAs) are essential membrane components in higher
      eukaryotes and are the precursors of many lipid-derived signaling molecules.
      Here, pathways for PUFA synthesis are described that do not require desaturation
      and elongation of saturated fatty acids. These pathways are catalyzed by
      polyketide synthases (PKSs) that are distinct from previously recognized PKSs in
      both structure and mechanism. Generation of cis double bonds probably involves
      position-specific isomerases; such enzymes might be useful in the production of
      new families of antibiotics. It is likely that PUFA synthesis in cold marine
      ecosystems is accomplished in part by these PKS enzymes.

PMID- 11452123
TI  - Endothelial apoptosis as the primary lesion initiating intestinal radiation
      damage in mice.
AB  - Gastrointestinal (GI) tract damage by chemotherapy or radiation limits their
      efficacy in cancer treatment. Radiation has been postulated to target epithelial
      stem cells within the crypts of Lieberkuhn to initiate the lethal GI syndrome.
      Here, we show in mouse models that microvascular endothelial apoptosis is the
      primary lesion leading to stem cell dysfunction. Radiation-induced crypt damage,
      organ failure, and death from the GI syndrome were prevented when endothelial
      apoptosis was inhibited pharmacologically by intravenous basic fibroblast growth
      factor (bFGF) or genetically by deletion of the acid sphingomyelinase gene.
      Endothelial, but not crypt, cells express FGF receptor transcripts, suggesting
      that the endothelial lesion occurs before crypt stem cell damage in the evolution
      of the GI syndrome. This study provides a basis for new approaches to prevent
      radiation damage to the bowel.

PMID- 11452124
TI  - Molecular evolution of protein atomic composition.
AB  - Living organisms encounter various growth conditions in their habitats, raising
      the question of whether ecological fluctuations could alter biological
      macromolecules. The advent of complete genome sequences and the characterization
      of whole metabolic pathways allowed us to search for such ecological imprints.
      Significant correlations between atomic composition and metabolic function were
      found in sulfur- and carbon-assimilatory enzymes, which appear depleted in sulfur
      and carbon, respectively, in both the bacterium Escherichia coli and the
      eukaryote Saccharomyces cerevisiae. In addition to genetic instructions, genomic
      data thus also provide paleontological records of environmental nutrient
      availability and of metabolic costs.

PMID- 11452125
TI  - Impairment of mycobacterial but not viral immunity by a germline human STAT1
      mutation.
AB  - Interferons (IFN) alpha/beta and gamma induce the formation of two
      transcriptional activators: gamma-activating factor (GAF) and interferon
      stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline
      STAT1 mutation associated with susceptibility to mycobacterial but not viral
      disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant
      for one cellular phenotype and recessive for the other. It impairs the nuclear
      accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs.
      Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are
      principally mediated by GAF.

PMID- 11452126
TI  - Interferon-gamma-mediated site-specific clearance of alphavirus from CNS neurons.
AB  - Recovery from viral encephalomyelitis requires immune-mediated noncytolytic
      clearance from neurons by mechanisms assumed to be the same for all neurons. In
      alphavirus encephalomyelitis, antibody clears infectious virus from neurons in
      all regions of the central nervous system (CNS), but CD8 T cells contribute to
      elimination of viral RNA. To understand the role of T cells in clearance, we
      infected antibody knockout mice with Sindbis virus. Virus was cleared from spinal
      cord and brain stem neurons, but not from cortical neurons, and required both CD4
      and CD8 T cells. Infection with cytokine-expressing recombinant viruses suggested
      that T cells used interferon-gamma, but not tumor necrosis factor alpha, in
      clearing virus and that populations of neurons differ in responsiveness to this
      effector pathway.

PMID- 11452127
TI  - Homeostatic regulation of the immune system by receptor tyrosine kinases of the
      Tyro 3 family.
AB  - Receptor tyrosine kinases and their ligands mediate cell-cell communication and
      interaction in many organ systems, but have not been known to act in this
      capacity in the mature immune system. We now provide genetic evidence that three
      closely related receptor tyrosine kinases, Tyro 3, Axl, and Mer, play an
      essential immunoregulatory role. Mutant mice that lack these receptors develop a
      severe lymphoproliferative disorder accompanied by broad-spectrum autoimmunity.
      These phenotypes are cell nonautonomous with respect to lymphocytes and result
      from the hyperactivation of antigen-presenting cells in which the three receptors
      are normally expressed.

PMID- 11452128
TI  - Regional mu opioid receptor regulation of sensory and affective dimensions of
      pain.
AB  - The endogenous opioid system is involved in stress responses, in the regulation
      of the experience of pain, and in the action of analgesic opiate drugs. We
      examined the function of the opioid system and mu-opioid receptors in the brains
      of healthy human subjects undergoing sustained pain. Sustained pain induced the
      regional release of endogenous opioids interacting with mu-opioid receptors in a
      number of cortical and subcortical brain regions. The activation of the mu-opioid
      receptor system was associated with reductions in the sensory and affective
      ratings of the pain experience, with distinct neuroanatomical involvements. These
      data demonstrate the central role of the mu-opioid receptors and their endogenous
      ligands in the regulation of sensory and affective components of the pain
      experience.

PMID- 11452129
TI  - Developmental toxicity of a triazole fungicide: consideration of interorgan
      communication.

PMID- 11452130
TI  - The Society of Toxicology's 1977 actions on laboratory accreditation,
      professional certification, and good laboratory practices in toxicology.

PMID- 11452131
TI  - A physiologically based pharmacokinetic model for methyl tert-butyl ether in
      humans: implementing sensitivity and variability analyses.
AB  - Methyl tert-butyl ether (MTBE) is added to gasoline to reduce carbon monoxide and
      ozone precursors from automobile emissions. The objectives of this study were to
      verify the ability of a physiologically based pharmacokinetic (PBPK) model to
      predict MTBE blood levels in humans and to investigate the effect of variability
      in the metabolism of MTBE and its influence on the predicted MTBE blood levels.
      The model structure for MTBE was flow-limited and had six essential compartments:
      lung, liver, rapidly perfused tissues, slowly perfused tissues, fat, and kidney.
      In this model, two pathways of metabolism are described to occur in the liver by
      Michaelis-Menten kinetics. Metabolic rate constants were measured in vitro using
      human liver microsomes and extrapolated to in vivo whole-body metabolism. Model
      predictions were compared with data on blood levels of MTBE taken from humans
      during and after a 1-h inhalation exposure to 1.7 ppm MTBE and after 4-h
      inhalation exposures to 4 or 40 ppm MTBE. The PBPK model accurately predicted
      MTBE pharmacokinetics at the high and low MTBE exposure concentrations for all
      time points. At the intermediate MTBE exposure concentration, however, the model
      underpredicted early time points while adequately predicting later time points.
      Results of the sensitivity analysis indicated that the influence of metabolic
      parameters on model output was dependent on MTBE exposure concentration.
      Subsequent variability analysis indicated that there was more variability in the
      actual measured MTBE blood levels than in the blood levels predicted by the PBPK
      model when using the range of metabolic parameters measured in vitro in human
      liver samples. By incorporating an understanding of the metabolic processes, this
      PBPK model can be used to predict blood levels of MTBE, which is important in
      determining target tissue dose estimates for risk assessment.

PMID- 11452132
TI  - Disposition and biotransformation of the estrogenic isoflavone daidzein in rats.
AB  - Daidzein is an estrogenic isoflavone present in many plants and therefore
      consumed in relatively high doses by humans. Daidzein has a low affinity for the
      estrogen receptor (3 orders of magnitude lower than estradiol) and has been
      demonstrated to have estrogenic effects in rodents after administration of high
      doses. We have studied the disposition and biotransformation of daidzein in rats
      fed a diet low in isoflavone content. Four male and four female Fischer 344 rats
      were orally administered 100 mg/kg daidzein; excreted urine and feces were
      collected for 96 h and unchanged daidzein as well as formed metabolites were
      quantified by HPLC. In urine of male rats, daidzein, daidzein-glucuronide, and
      daidzein-sulfate were excreted; in females, only unchanged daidzein and daidzein
      glucuronide were present. Total urinary excretion of daidzein accounted for < 10%
      of dose in both males and females. The major pathway of daidzein elimination was
      excretion of unchanged daidzein with feces. Reductive daidzein-metabolites likely
      formed by intestinal microflora (equol, O-desmethylangolensin) were excreted with
      feces in small amounts (< 5% of dose). Excretion of daidzein and metabolites with
      urine and feces was rapid with elimination half-lives of less than 12 h; daidzein
      concentrations in urine and feces were below the limit of detection 36 h after
      daidzein administration. The results suggest that daidzein is only poorly
      absorbed from the gastrointestinal tract in rodents. Absorbed daidzein is rapidly
      eliminated both unchanged and as conjugates with urine. The inefficient
      absorption of daidzein from the gastrointestinal tract and the rapid excretion
      may explain the weak estrogenicity of daidzein seen in vivo in rodents when
      compared to other estrogenic chemicals with comparatively low affinity to the
      estrogen receptor.

PMID- 11452133
TI  - Vascular and hepatocellular peroxynitrite formation during acetaminophen
      toxicity: role of mitochondrial oxidant stress.
AB  - Peroxynitrite may be involved in acetaminophen-induced liver damage. However, it
      is unclear if peroxynitrite is generated in hepatocytes or in the vasculature. To
      address this question, we treated C3Heb/FeJ mice with 300 mg/kg acetaminophen and
      assessed nitrotyrosine protein adducts as indicator for peroxynitrite formation.
      Vascular nitrotyrosine staining was evident before liver injury between 0.5 and 2
      h after acetaminophen treatment. However, liver injury developed parallel to
      hepatocellular nitrotyrosine staining between 2 and 6 h after acetaminophen. The
      mitochondrial content of glutathione disulfide, as indicator of reactive oxygen
      formation determined 6 h after acetaminophen, increased from 2.8 +/- 0.6% in
      controls to 23.5 +/- 5.1%. A high dose of allopurinol (100 mg/kg) strongly
      attenuated acetaminophen protein-adduct formation and prevented the mitochondrial
      oxidant stress and liver injury after acetaminophen. Lower doses of allopurinol,
      which are equally effective in inhibiting xanthine oxidase, were not protective
      and had no effect on nitrotyrosine staining and acetaminophen protein adduct
      formation. In vitro experiments showed that allopurinol is not a direct scavenger
      of peroxynitrite. We conclude that there is vascular peroxynitrite formation
      during the first 2 h after acetaminophen treatment. On the other hand, reactive
      metabolites of acetaminophen bind to intracellular proteins and cause
      mitochondrial dysfunction and superoxide formation. Mitochondrial superoxide
      reacts with nitric oxide to form peroxynitrite, which is responsible for
      intracellular protein nitration. The pathophysiological relevance of vascular
      peroxynitrite for hepatocellular peroxynitrite formation and liver injury remains
      to be established.

PMID- 11452134
TI  - Metabolic activation of bisphenol A by rat liver S9 fraction.
AB  - Bisphenol A (BPA) is a well-known endocrine-disrupting chemical found in the
      environment. To assess the metabolic modulation of estrogenic activity of BPA
      after ingestion, we investigated whether the incubation of BPA with rat liver S9
      fraction results in metabolic activation or inactivation of estrogenic activity
      using a recombinant yeast expressing human estrogen receptor and MCF-7
      transfected firefly luciferase plasmid for a reporter assay. When 0.1 mM BPA was
      incubated with rat liver S9 for 1 h, the estrogenic activity was increased about
      two to five times compared with that of the control, in which the S9 was
      inactivated prior to incubation. This metabolic activation was inhibited by SKF
      525-A, an inhibitor of cytochrome P450. With increasing incubation time, the
      estrogenic activity increased time-dependently. Interestingly, however, the
      metabolic activation did not proceed with either microsomes or cytosol alone and
      was restored by a recombination of both fractions. The active metabolite was
      eluted at later retention time than that of BPA on HPLC with a reversed-phase
      column. Bisphenol B and methoxychlor were also activated by incubation with rat
      liver S9, whereas 4-tert-octylphenol and 4-nonylphenol, as well as 17beta
      estradiol, were metabolically inactivated. The present results clearly indicate
      that BPA is metabolically activated in terms of estrogenicity under the
      conditions existing only with combined rat liver microsomes and cytosol.

PMID- 11452135
TI  - Characterization of tert-butyl alcohol binding to alpha2u-globulin in F-344 rats.
AB  - tert-Butyl alcohol (TBA) is widely used in the manufacturing of certain perfumes,
      cosmetics, drugs, paint removers, methyl tert-butyl ether (MTBE), and industrial
      solvents. In both rodents and humans, TBA is a major metabolite of MTBE, an
      oxygenated fuel additive. Chronic TBA exposure causes protein droplet
      nephropathy, alpha2u-globulin (alpha2u) accumulation, renal cell proliferation,
      and with chronic exposure, renal tumors in male, but not female, rats. These
      effects suggest an alpha2u-mediated mechanism for renal tumors. The objective of
      the present study was to determine whether TBA or its metabolites bind to
      alpha2u. Mature male and female F-344 rats were administered a single gavage dose
      of 500 mg/kg TBA, 500 mg/kg (14)C-TBA, or corn oil. TBA equivalents/gram or ml of
      tissue in the male rat kidney, liver, and blood were higher than the levels
      measured in female rat tissue 12 h after (14)C-TBA administration. Gel filtration
      and anion-exchange chromatography demonstrated that (14)C-TBA-derived
      radioactivity co-eluted with alpha2u from male kidney cytosol. Protein dialysis
      studies demonstrated that the interaction between (14)C-TBA-derived radioactivity
      and alpha2u was reversible. Incubations of the low-molecular-weight protein
      fraction (LMWPF) isolated from (14)C-TBA-treated male rat kidneys with d-limonene
      oxide (a chemical with a high affinity to alpha2u) demonstrated that (14)C-TBA
      derived radioactivity was displaced. Gas chromatography-mass spectrometry
      analysis confirmed that TBA was present in this LMWPF fraction. These results
      demonstrate that TBA interacts with alpha2u, which explains the accumulation of
      alpha2u in the male rat kidney following TBA exposure.

PMID- 11452136
TI  - Androgen-mediated development in male rat offspring exposed to flutamide in
      utero: permanence and correlation of early postnatal changes in anogenital
      distance and nipple retention with malformations in androgen-dependent tissues.
AB  - Male offspring exposed in utero to antiandrogens often display alterations in
      androgen-dependent developmental markers (e.g., anogenital distance [AGD], nipple
      retention) together with clearly adverse responses such as genital malformations
      and reproductive tract lesions. The objectives of this study were to determine
      whether in utero exposure to flutamide results in permanent changes in male AGD
      and nipple retention, characterize the dose-response relationship between
      flutamide-mediated alterations in these landmarks and clearly adverse
      antiandrogenic effects, and establish the predictive value and relationship
      between AGD and nipple retention, and other adverse manifestations. Male
      offspring were exposed in utero to 0, 6.25, 12.5, 25, or 50 mg/kg/day (po) of
      flutamide from gestation days 12 to 21. Offspring were uniquely identified at
      birth, and various androgen-mediated end points (AGD, areola/nipple retention,
      cryptorchidism, reproductive tract weights, and malformation incidence) were
      examined throughout life. In utero flutamide exposure significantly decreased the
      AGD on postnatal day (PND) 1 and increased areola/nipple retention in male rats
      on PND 13. Flutamide-induced alterations in AGD and areolae/nipples in early
      postnatal life correlated with a reduction in AGD and retained nipples observed
      in the adult. Prenatal flutamide exposure resulted in dose-responsive increases
      in cryptorchidism. Hypospadias were observed in all flutamide-exposed offspring.
      In utero flutamide exposure induced partial or complete prostate agenesis and
      decreased the weights of the seminal vesicles, levator ani bulbocavernosus (LABC)
      muscle, testes, and epididymides in a dose-dependent manner. Epididymal
      malformations were observed mainly in the 50 mg/kg/day flutamide dose group. In
      general, flutamide-induced alterations in dihydrotestosterone (DHT)- and
      testosterone (T)-dependent development each had similar respective dose-response
      curves. DHT-mediated development was more sensitive to in utero flutamide
      exposure than T-dependent processes. However, the dose-response curves for
      flutamide-induced changes in cryptorchidism and seminal vesicle weight were
      intermediate between the dose-response curves for DHT- and T-mediated
      development, indicating that proper development of these tissues may require both
      androgens. The LABC also displayed a dose-dependent decrease in weight that was
      similar to dose-response observed with seminal vesicle weight and was the most
      sensitive T-dependent end point measured. Flutamide-induced decreases in AGD
      predicted subsequent malformations as evidenced by logistic regression and
      receiver operator characteristic analysis of malformations versus AGD. However,
      the AGD that would predict a 10% incidence of seminal vesicle malformations is
      equivalent to a female AGD. An almost fully feminized phenotype of 10-12 nipples
      was observed in animals that had malformations in T-dependent tissues, whereas 6
      or more nipples were observed in animals with malformation in DHT-dependent
      tissues. These data suggest that flutamide-mediated changes in AGD and nipple
      retention are not sensitive predictors of altered T-mediated development.

PMID- 11452137
TI  - C57BL/6 mice are resistant to acute restraint modulation of cutaneous
      hypersensitivity.
AB  - C57BL/6 mice, in contrast to BALB/c mice, display minimal behavioral changes in
      response to environmental stressors and are considered relatively stress
      resistant. We have shown that application of acute restraint prior to chemical
      challenge enhanced cutaneous hypersensitivity (CHS) in BALB/c mice and that this
      enhanced response is partially glucocorticoid dependent. Due to strain
      differences in the immune response and in the response to environmental
      stressors, we hypothesized that acute restraint would not enhance CHS in the less
      stress-sensitive C57BL/6 mice. We sensitized and challenged C57BL/6 mice with the
      contact sensitizer, 2, 4-dinitrofluorobenzene (DNFB) in the presence and absence
      of restraint. Acute restraint, applied prior to chemical challenge, significantly
      increased serum corticosterone, but to concentrations approximately 60% of those
      reported for BALB/c mice. Neither restraint nor the exogenous administration of
      corticosterone enhanced chemical-induced ear swelling in C57BL/6 mice.
      Pharmacological interruption of the hypothalamic pituitary adrenal axis (HPAA)
      with the glucocorticoid type II receptor antagonist, RU486, did not alter the
      development of CHS, however, adrenalectomized (ADX) mice exhibited decreased ear
      swelling, a measurement that was decreased further by restraint. Combined
      application of acute restraint and corticosterone prior to chemical challenge
      significantly enhanced the ear swelling response in C57BL/6 wild-type mice. These
      data confirm that C57BL/6 mice have a blunted corticosterone response to
      restraint and that acute restraint does not modulate cutaneous hypersensitivity.
      Furthermore, our data demonstrate that stress-resistance is not conferred
      exclusively through the glucocorticoid pathways.

PMID- 11452138
TI  - Masculinization of female mosquitofish in Kraft mill effluent-contaminated
      Fenholloway River water is associated with androgen receptor agonist activity.
AB  - Female mosquitofish (Gambusia affinis holbrooki) downstream from Kraft paper
      mills in Florida display masculinization of the anal fin, an androgen-dependent
      trait. The current investigation was designed to determine if water contaminated
      with pulp-mill effluent (PME) from the Fenholloway River in Florida displayed
      androgenic activity in vitro and to relate this activity to the reproductive
      status of female mosquitofish taken from this river. We tested water samples for
      androgenic activity from a reference site upstream of a Kraft pulp and paper mill
      on the Fenholloway River, from 3 sites downstream from the mill, and from another
      reference site on the Econfina River, also in Florida, where there is no paper
      mill. We also examined anal fin ray morphology in mosquitofish from these rivers
      for evidence of masculinization. Eighty percent of the female mosquitofish from
      the Fenholloway River were partially masculinized while another 10% were
      completely masculinized, based upon the numbers of segments in the longest anal
      fin ray (18.0 +/- 0.4 vs. 28.1 +/- 0.9 [p < 0.001]) in the Econfina River vs. the
      Fenholloway River, respectively). In a COS whole cell-binding assay, all 3 PME
      samples displayed affinity for human androgen receptor (hAR) (p < 0.001). In
      addition, PME induced androgen-dependent gene expression in CV-1 cells
      (cotransfected with pCMV hAR and MMTV luciferase reporter), which was inhibited
      by about 50% by coadministration of hydroxyflutamide (1 microM), an AR
      antagonist. Water samples collected upstream of the Kraft mill or from the
      Econfina River did not bind hAR or induce luciferase expression. When CV-1 cells
      were transfected with human glucocorticoid receptor (hGR) rather than hAR, PME
      failed to significantly induce MMTV-luciferase expression. Further evidence of
      the androgenicity was observed using a COS cell AR nuclear-translocalization
      assay. PME bound hAR and induced translocalization of AR into the nucleus. In
      contrast, AR remained perinuclear when treated with water from the control sites
      (indicating the absence of an AR ligand). Interestingly, PME also displayed
      "testosterone-like" immunoreactivity in a testosterone radioimmunoassay, whereas
      water from the reference sites did not. In summary, water collected downstream of
      the Kraft mill on the Fenholloway River contains unidentified androgenic
      substances whose presence is associated with masculinization of female
      mosquitofish.

PMID- 11452139
TI  - Low exposure concentration effects of methoprene on endocrine-regulated processes
      in the crustacean Daphnia magna.
AB  - Methoprene is a growth-regulating insecticide that manifests its toxicity to
      target organisms by acting as a juvenile hormone agonist. Methoprene similarly
      may exert toxicity to crustaceans by mimicking or interfering with methyl
      farnesoate, a crustacean juvenoid. We hypothesized that methoprene interferes
      with endocrine-regulated processes in crustaceans by several mechanisms involving
      agonism or antagonism of juvenoid receptor complexes. In the present study, we
      evaluated this hypothesis, in part, by characterizing and comparing the
      concentration-response curves for methoprene and several endpoints related to
      development and reproduction of the crustacean Daphnia magna. Our results
      demonstrate that methoprene has multiple mechanisms of toxicity and low-exposure
      concentration effects. Methoprene reduced the growth rate of daphnids with
      evidence of only a single concentration-response line, having a threshold of 12.6
      nM. Molt frequency was reduced by methoprene in a concentration-dependent manner,
      with a response curve corresponding to a 2-segmented line and thresholds at 4.2
      and 0.21 nM. An endpoint related to reproductive maturation, the time of first
      brood deposition, was also affected by methoprene, with a clear concentration
      dependent response and a NOEC of 32 nM. Methoprene reduced fecundity according to
      a 2-segmented line, with thresholds of 24 and < or =0.18 nM. These results
      demonstrate that methoprene elicits significant toxicity to endocrine-related
      processes in the 5-50 nM concentration range. Furthermore, molting and
      reproduction were impacted at significantly lower methoprene concentrations, with
      a distinct concentration response and a threshold of < or =0.2 nM. The different
      concentration-dependent response from that of methoprene could involve agonism or
      antagonism of various juvenoid receptor configurations.

PMID- 11452140
TI  - Effects of S-ethyl hexahydro-1H-azepine-1-carbothioate (molinate) on di-n-butyl
      dichlorovinyl phosphate (DBDCVP) neuropathy.
AB  - Certain esterase inhibitors protect from organophosphate-induced delayed
      polyneuropathy (OPIDP) when given before a neuropathic organophosphate by
      inhibiting neuropathy target esterase (NTE). In contrast, they can exaggerate
      OPIDP when given afterwards and this effect (promotion) is associated with
      inhibition of another esterase (M200). In vitro sensitivities of hen, rat, and
      human NTE and M200 to the active metabolites of molinate, sulfone, and sulfoxide,
      were similar. NTE and M200 were irreversibly inhibited (> 78%) in brain and
      peripheral nerve of hens and rats given molinate (100-180 mg/kg, sc). No clinical
      or morphological signs of neuropathy developed in these animals. Hens and rats
      were protected from di-n-butyl dichlorovinyl phosphate neuropathy (DBDCVP, 1 and
      5 mg/kg, sc, respectively) by molinate (180 or 100 mg/kg, sc, 24 h earlier,
      respectively) whereas 45 mg/kg, sc molinate causing about 34% NTE inhibition
      offered partial protection to hens. Hens treated with DBDCVP (0.4 mg/kg, sc)
      developed a mild OPIDP; molinate (180 mg/kg, 24 h later) increased the severity
      of clinical effects and of histopathology in spinal cord and in peripheral
      nerves. Lower doses of molinate (45 mg/kg, sc), causing about 47% M200
      inhibition, did not promote OPIDP whereas the effect of 90 mg/kg, sc
      (corresponding to about 50-60% inhibition) was mild and not statistically
      significant. OPIDP induced by DBDCVP (5 mg/kg, sc) in rats was promoted by
      molinate (100 mg/kg, sc). In conclusion, protection from DBDCVP neuropathy by
      molinate is correlated with inhibition of NTE whereas promotion of DBDCVP
      neuropathy is associated with > 50% M200 inhibition.

PMID- 11452141
TI  - Associations of lead exposure and dose measures with erythrocyte protein kinase C
      activity in 212 current Korean lead workers.
AB  - Lead can replace calcium in enzyme assays that measure protein kinase C activity
      and lead activates protein kinase C in human erythrocytes after exposure to lead
      in vitro. To examine the relevance of these observations to lead exposure in
      humans, we studied the associations of lead found in blood or tibia with
      activation of protein kinase C in erythrocytes isolated from workers in the lead
      industry. We examined erythrocytes among 212 lead workers, with a mean (+/-SD)
      age of 39.1 (10.0) years and exposure duration of 8.1 (6.5) years and measured
      protein kinase C activation by an in vitro back-phosphorylation assay. After
      adjustment for potential confounding factors (age and sex), tibia lead and
      exposure duration were significantly associated with erythrocyte protein kinase C
      activation (both p values < 0.05). No associations were observed between protein
      kinase C activation and blood-lead or zinc-protoporphyrin levels. These findings
      suggest that human exposure to lead results in activation of erythrocyte protein
      kinase C, which may be directly relevant to the neurotoxicity of lead.

PMID- 11452142
TI  - Expression of AhR and ARNT mRNA in cultured human endometrial explants exposed to
      TCDD.
AB  - Endometriosis is a debilitating disease found in 10-15% of reproductive-age women
      and is characterized by the presence of endometrial tissue outside of the uterus.
      The present study characterizes the expression of AhR and ARNT mRNA in a human
      endometrial explant culture model in the absence and presence of TCDD exposure.
      In a parallel, companion study using this model, TCDD exposure was shown to
      induce CYP1A1 mRNA, CYP1B1 mRNA, EROD (7-ethoxyresorufin-O-deethylase) activity,
      and CYP1B1 protein in human endometrial explants. Explants were prepared from
      specimens obtained at laparoscopy or laparotomy from women undergoing surgery for
      tubal ligation, endometriosis, or pelvic pain unrelated to endometriosis. These
      specimens were a subset of the specimens used in the parallel study. The explants
      were cultured in medium containing 10 nM estradiol (E(2)) or 1 nM estradiol plus
      500 nM progesterone (E(2) + P(4)) with or without TCDD (first 24 h). After
      culture, AhR and ARNT mRNA expression were quantified by RT-PCR. TCDD treatment
      significantly increased the expression of AhR mRNA, but not ARNT mRNA. The
      expression of both genes was similar for all individual explants and the ratio of
      AhR:ARNT mRNA expression across all samples was 1.7 to 1.8. Constitutive AhR mRNA
      expression was donor age dependent (increasing with age), while ARNT mRNA
      expression was donor age and tissue phase dependent (increased in older and
      proliferative phase specimens). Similar to results in the parallel study on
      expression of CYP1A1 mRNA, CYP1B1 mRNA, EROD activity, and CYP1B1 protein, the
      presence of endometriosis did not affect the expression of AhR or ARNT mRNA,
      either constitutively or following TCDD exposure. However, the detection of
      disease-specific change was limited by small sample size and variability in
      tissue cycle phase. The human endometrial explant culture model will be useful
      for future studies of the effects of dioxin-like compounds on human endometrium
      in relationship to cycle phase, hormonal exposure, and donor age.

PMID- 11452143
TI  - Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of
      human endometrium.
AB  - Endometriosis is a debilitating disease estimated to affect 10% of reproductive
      age women and characterized by the growth of endometrial tissue outside of the
      uterus. The present study characterizes a human endometrial explant culture model
      for studying the direct effects of TCDD exposure by assessing the expression of
      CYP1A1 and CYP1B1 mRNA (Northern blotting), protein (Western blotting), and
      activity (7-ethoxyresorufin-O-deethylase; EROD) in explants cultured with and
      without TCDD. Explants were obtained at laparoscopy or laparotomy from women
      undergoing surgery for tubal ligation, endometriosis, or pelvic pain unrelated to
      endometriosis. The explants were cultured with 10 nM estradiol (E(2)) or 1 nM
      E(2) plus 500 nM progesterone (P(4)) with or without TCDD (first 24 h). The
      expression of CYP1A1 and CYP1B1 mRNA was greatest with 10 nM TCDD and increased
      up to 72 h after initial exposure. EROD activity increased up to 120 h. Explants
      from a secretory phase biopsy became reorganized in culture and formed a new
      epithelial membrane, while maintaining basic endometrial morphology and viability
      for up to 120 h. At 24 h, TCDD significantly increased CYP1A1 and CYP1B1 mRNA,
      and at 72 h, TCDD significantly increased EROD activity and CYP1B1 protein
      compared to explants cultured without TCDD for similar times. CYP1B1 protein also
      exhibited substantial constitutive expression that was similar in uncultured
      biopsies, where CYP1B1 protein was immunolocalized in the cytoplasm of epithelial
      glands, with only occasional patches of protein in the surface epithelial
      membrane. In explants cultured with and without TCDD exposure, CYP1B1 protein was
      localized in the cytoplasm of the new surface epithelial membrane and glands
      closest to the surface. CYP1A1 protein was not detected in uncultured biopsies or
      explants. Both younger age (age 30 and under) and proliferative phase were
      associated with higher TCDD-induced EROD activity in specimens treated with
      E(2):P(4). No significant endometriosis-related differences were observed for any
      of the biomarkers, but the detection of disease-specific change was limited by
      small sample size and variability in tissue-cycle phase. The human endometrial
      explant culture model will be useful for future studies of the effects of dioxin
      like compounds on human endometrium in relationship to cycle phase and hormonal
      exposure.

PMID- 11452144
TI  - Effect of 4-vinylcyclohexene diepoxide dosing in rats on GSH levels in liver and
      ovaries.
AB  - Repeated daily dosing of rats with the occupational chemical 4- vinylcyclohexene
      or its diepoxide metabolite (VCD) for 15 days destroys the smallest ovarian
      follicles. VCD acutely reduced hepatic levels of the antioxidant, glutathione
      (GSH); therefore, these studies were designed to evaluate whether GSH
      concentrations mediate VCD-induced ovotoxicity. Immature female Fischer 344 rats
      were dosed once or daily for 15 days with VCD (0.57 mmol/kg, ip) or the GSH
      synthesis inhibitor buthionine sulfoximine (BSO, 2 mmol/kg, ip). Animals were
      euthanized 2, 6, or 26 h following a single dose, and 2 or 26 h following 15 days
      of daily dosing. Reduced (p < 0.05) hepatic GSH was seen within 2 h of a single
      dose of either VCD (51 +/- 5% of control) or BSO (42 +/- 9%), but only BSO
      reduced ovarian GSH (71 +/- 5% at 6 h, p = 0.05) as measured by HPLC. Within 26
      h, GSH levels had returned to control levels with either treatment. Hepatic GSH
      levels were reduced (< 0.05) 2 h after 15 daily doses with BSO (42 +/- 5%) or VCD
      (70 +/- 4%), but only BSO decreased ovarian GSH (64 +/- 3%). GSH levels in 15-day
      tissues were similar to controls 26 h after the final dose. Neither BSO nor VCD
      increased hepatic or ovarian concentrations of the oxidized dimer of GSH (GSSG)
      or thiobarbituric acid-reactive substances (TBARS), indicators of oxidative
      stress. These results suggest these treatments did not cause an oxidative stress.
      Histological counts of ovarian small follicle numbers were reduced (p < 0.05) in
      15-day VCD-treated rats, whereas BSO did not affect follicle numbers, even though
      BSO reduced ovarian GSH content. These results support the conclusion that
      alterations in ovarian GSH levels are not involved in VCD-induced ovotoxicity.

PMID- 11452145
TI  - Skeletal effects of developmental lead exposure in rats.
AB  - To identify possible direct and indirect mechanisms underlying the effects of
      lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and
      1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475
      ppm lead acetate in the drinking water from gestational day 4 to euthanasia on
      day 55. Tibial strength was tested by 3-point bending and plasma levels of
      vitamin D metabolites were measured. A dose-dependent decrease of the load to
      failure was demonstrated but only in male pups. No differences in plasma levels
      of vitamin D metabolites were observed. In the second study, conducted to test if
      hormone treatment would attenuate the lead deficits, male and female pups were
      exposed to 0 or 2475 ppm lead acetate and then, from 30-60 days of age, received
      either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone
      (DHT, males only), or estradiol (females only). Lead exposure significantly
      reduced somatic growth, longitudinal bone growth, and bone strength during the
      pubertal period. Sex steroid replacement did not restore skeletal parameters in
      lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF(1))
      concentrations, rates of bone growth, and bone strength measures in controls
      while having no effect in lead-exposed pups. The third study was conducted at 100
      days of age, when endocrine parameters have been shown to be normalized, to test
      for effects of lead exposure on bone formation during tibial limb lengthening
      (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new
      endosteal bone formation were decreased in the distraction gaps of the lead
      treated animals (p < 0.01). In conclusion, lead exposure reduced somatic growth,
      longitudinal bone growth, and bone strength during the pubertal period, and these
      effects could not be reversed by a growth hormone (GH) axis stimulator or by sex
      appropriate hormones. Finally, lead exposure appears to specifically inhibit
      osteoblastogenesis in vivo in adult animals.

PMID- 11452146
TI  - The frequency of U-shaped dose responses in the toxicological literature.
AB  - Hormesis has been defined as a dose-response relationship in which there is a
      stimulatory response at low doses, but an inhibitory response at high doses,
      resulting in a U- or inverted U-shaped dose response. To assess the proportion of
      studies satisfying criteria for evidence of hormesis, a database was created from
      published toxicological literature using rigorous a priori entry and evaluative
      criteria. One percent (195 out of 20,285) of the published articles contained 668
      dose-response relationships that met the entry criteria. Subsequent application
      of evaluative criteria revealed that 245 (37% of 668) dose-response relationships
      from 86 articles (0.4% of 20,285) satisfied requirements for evidence of
      hormesis. Quantitative evaluation of false-positive and false-negative responses
      indicated that the data were not very susceptible to such influences. A
      complementary analysis of all dose responses assessed by hypothesis testing or
      distributional analyses, where the units of comparison were treatment doses below
      the NOAEL, revealed that of 1089 doses below the NOAEL, 213 (19.5%) satisfied
      statistical significance or distributional data evaluative criteria for hormesis,
      869 (80%) did not differ from the control, and 7 (0.6%) displayed evidence of
      false-positive values. The 32.5-fold (19.5% vs 0.6%) greater occurrence of
      hormetic responses than a response of similar magnitude in the opposite
      (negative) direction strongly supports the nonrandom nature of hormetic
      responses. This study, which provides the first documentation of a data-derived
      frequency of hormetic responses in the toxicologically oriented literature,
      indicates that when the study design satisfies a priori criteria (i.e., a well
      defined NOAEL, > or = 2 doses below the NOAEL, and the end point measured has the
      capacity to display either stimulatory or inhibitory responses), hormesis is
      frequently encountered and is broadly represented according to agent, model, and
      end point. These findings have broad-based implications for study design, risk
      assessment methods, and the establishment of optimal drug doses and suggest
      important evolutionarily adaptive strategies for dose-response relationships.

PMID- 11452147
TI  - The effects of perinatal tebuconazole exposure on adult neurological,
      immunological, and reproductive function in rats.
AB  - Studies are under way to address concerns of potential persistent immunotoxic,
      reproductive, and neurotoxic effects of perinatal exposure to several pesticides.
      Tebuconazole, a triazole fungicide, was evaluated as part of this project.
      Sprague-Dawley dams were administered tebuconazole (0, 6, 20, or 60 mg/kg) by
      oral gavage daily from gestational day 14 to postnatal day (PND)7; the pups were
      then dosed daily at the same levels from PND7-42. Separate groups of rats were
      used for testing of immunological parameters, neurobehavioral testing using a
      screening battery of functional tests, and cognitive evaluations. Other groups of
      rats were evaluated for reproductive development and function, while yet others
      were sacrificed at the end of the dosing period for histological analyses of
      major organs systems, including neuropathological assessments. Pup viability and
      body weight were decreased in the highest dose group. There were no differences
      in the fertility indices in the exposed rats mated as adults. In the sheep RBC
      immunized high-dose rats, spleen weights and cellularity were increased, and the
      ratio of cell types was altered compared to controls. There were, however, no
      biologically significant changes in the immune function of these rats. At
      necropsy on PND46 or 152, kidney, liver, and spleen weights were altered by
      tebuconazole treatment, but a dose-response relationship was not clear for most
      organs; only decreased kidney and increased liver weights were consistent in both
      sexes. Histological analyses were generally unremarkable outside of the brain.
      One month after the end of dosing, acquisition of learning the platform location
      in a water tank (i.e., Morris water maze) was impaired in the high-dose group;
      there were no differences in neuromuscular ability, motor activity, or swim speed
      to account for this finding. Furthermore, there was no effect on recall of the
      position during a free-swim trial. Neuropathological evaluations revealed
      pyknotic cells across hippocampal cell fields in animals of all tebuconazole
      treatment groups, with the highest incidence in the 20 and 60 mg/kg/day dose
      groups, coincident with cell loss within pyramidal cell layer of CA3-4 cell
      fields of the hippocampus and layer V of the neocortex. Thus, perinatal exposure
      to tebuconazole produced neurobehavioral deficits and neuropathology in rats, but
      did not alter immunological or reproductive function.

PMID- 11452150
TI  - Re.: Toxicologists and the founding of the Society of Toxicology.

PMID- 11452148
TI  - Favism: effect of divicine on rat erythrocyte sulfhydryl status, hexose
      monophosphate shunt activity, morphology, and membrane skeletal proteins.
AB  - Favism is an acute anemic crisis that can occur in susceptible individuals who
      ingest fava beans. The fava bean pyrimidine aglycone divicine has been identified
      as a hemotoxic constituent; however, its mechanism of toxicity remains unknown.
      We have shown recently that divicine can induce a favic-like response in rats and
      that divicine is directly toxic to rat red cells. In the present study, we have
      examined the effect of hemotoxic concentrations of divicine on rat erythrocyte
      sulfhydryl status, hexose monophosphate (HMP) shunt activity, morphology, and
      membrane skeletal proteins. In vitro exposure of rat red cells to divicine
      markedly stimulated HMP shunt activity and resulted in depletion of reduced
      glutathione with concomitant formation of glutathione-protein mixed-disulfides.
      Examination of divicine-treated red cells by scanning electron microscopy
      revealed transformation of the cells to an extreme echinocytic morphology. SDS
      PAGE and immunoblotting analysis of the membrane skeletal proteins indicated that
      hemotoxicity was associated with the apparent loss of skeletal protein bands 2.1,
      3, and 4.2, and the appearance of membrane-bound hemoglobin. Treatment of
      divicine-damaged red cells with dithiothreitol reversed the protein changes,
      which indicated that the observed alterations were due primarily to the formation
      of disulfide-linked hemoglobin-skeletal protein adducts. The data suggest that
      oxidative modification of hemoglobin and membrane skeletal proteins by divicine
      may be key events in the mechanism underlying favism.

PMID- 11452151
TI  - Cellular engineering for the production of blood components.

PMID- 11452152
TI  - Single-donor platelets reduce the risk of septic platelet transfusion reactions.
AB  - BACKGROUND: Septic platelet transfusion reactions (SPTRs) are the most common,
      serious risk of transfusion. Because SPTRs result from donor skin flora or
      asymptomatic bacteremia, the use of single-donor platelets (SDPs) has been
      proposed to reduce the risk of SPTRs from the risks with pools of platelet
      concentrates (PCs). STUDY DESIGN AND METHODS: Beginning in 1986, all febrile
      transfusion reactions were evaluated by culture of the platelet bag. Confirmed
      SPTRs were identified by isolation of the same bacteria from the bag and the
      patient's blood or by positive Gram's stain of the bag that confirmed a positive
      platelet culture. In 1987, a program to minimize PC use in favor of SDP use was
      initiated as a means of reducing SPTRs. RESULTS: In 12 years, the use of SDPs
      increased from 51.7 percent to 99.4 percent of all platelet transfusions at one
      institution. SPTRs fell from three events in 1 year to the current rate of one
      event per year. The incidence of SPTRs decreased from 1 in 4,818 transfusions to
      1 in 15,098 transfusions. The rate of SPTRs due to PCs was 5.39 times higher than
      that of SPTRs due to SDPs (95% CI, 1.89,12.9). CONCLUSION: The use of SDPs is a
      simple means of reducing SPTRs. Other measures such as sterilization will be
      required to eliminate all SPTRs.

PMID- 11452153
TI  - Determinants of transfusion-associated bacterial contamination: results of the
      French BACTHEM Case-Control Study.
AB  - BACKGROUND: Transfusion-associated bacterial contamination (TABC), probably the
      most frequent transfusion-transmitted infection, may induce serious adverse
      events. Systematic information and documentation on determinants are lacking.
      STUDY DESIGN AND METHODS: The BACTHEM Study is a French matched case-control
      study assessing TABC determinants. Included were cases of TABC reported in France
      in a 2-year period, as determined from uniform definitions. Information on
      recipient-, blood component-, and donor-related potential determinants was
      collected on site. ORs were estimated by conditional logistic regression.
      RESULTS: Of the 158 cases of suspected TABC reported, 41 that involved
      transfusion with 25 RBCs and 16 platelet concentrates were included. Gram
      negative rods accounted for nearly half of the bacteria species involved and for
      all six deaths. In comparison with the risk of TABC for patients receiving RBCs
      for anemia, the risk was higher for patients receiving RBCs for pancytopenia (OR,
      7.3; 95% CI, 1.3-41.0) and for those receiving platelets for thrombocytopenia
      (OR, 5.3; 95% CI, 1.2-24.1). Other potential determinants were platelet
      transfusion for pancytopenia (OR, 4.5; 95% CI, 0.5-40.0), immunosuppressive
      treatment (OR, 2.8; 95% CI, 0.7-10.6), shelf-life of more than 1 day for
      platelets or 8 days for RBCs (OR, 2.6; 95% CI, 0.7-9.6), and more than 20
      previous donations by donors (OR, 1.9; 95% CI, 0.7-5.3). CONCLUSION: This first
      comparative study revealed TABC determinants that suggest approaches for
      prevention.

PMID- 11452154
TI  - WBC-reduced blood transfusions and clinical outcome in children with acute
      lymphoid leukemia.
AB  - BACKGROUND: WBC reduction offers a variety of benefits to patients requiring
      multiple transfusions during induction therapy for childhood acute lymphoid
      leukemia (ALL), including reductions in febrile transfusion reactions, HLA
      alloimmunization, and CMV transmission. One potential benefit is a reduction in
      the deleterious effects of transfusion immunomodulation. In the surgical setting,
      transfusion immunomodulation has been linked to increases in postoperative
      infections and decreases in host cellular immunity that are mitigated by WBC
      reduction of transfused blood. STUDY DESIGN AND METHODS: A retrospective review
      was conducted of the medical records of 68 consecutive children undergoing
      induction therapy for newly diagnosed ALL from 1988 through 1995, a period whose
      midpoint is 1991, the year WBC reduction was introduced in this hospital.
      RESULTS: WBC reduction of platelet and RBC transfusions was associated with fewer
      days with fever (mean, 5.7 days [no WBC reduction] and 2.1 days [WBC reduction];
      p = 0.012) and days with positive microbial cultures (mean, 1.5 [no WBC
      reduction] and 0.71 [WBC reduction]; p = 0.0055). There were more high-risk ALL
      patients in the group receiving WBC-reduced transfusions. CONCLUSION: Allogeneic
      WBCs in transfused blood may cause impairment of host defenses against microbial
      infection during induction therapy for childhood ALL.

PMID- 11452155
TI  - Analysis of HBV infection after blood transfusion in Japan through investigation
      of a comprehensive donor specimen repository.
AB  - BACKGROUND: To understand the risk of transfusion-transmitted viral infection, it
      is important to precisely assess cases of infection that follow transfusion.
      STUDY DESIGN AND METHODS: HBV infections noted after transfusion in 1997, 1998,
      and 1999 were analyzed. Transfusion in all these cases was performed before NAT
      was adopted for donor screening. To detect viral infection, PCR and serologic
      tests for HBV were performed retrospectively on all blood samples from implicated
      donors that had been stored in a frozen state after each donation. The
      concentration of HBV genome was measured in HBV-positive blood samples. RESULTS:
      One hundred three cases of HBV infection were analyzed; of these, only 16,
      including at least 10 infections due to window-period (HBsAg-positive by reverse
      particle hemagglutination assay) donations, were confirmed by further testing to
      be related to transfusion. The concentrations of HBV genome were very low in four
      blood samples (<50, 400, 500, and 800 genome equivalents/mL of plasma).
      CONCLUSIONS: The remaining risk of transfusion transmission of HBV infection
      before the adoption of NAT was mainly due to window-period donations, including
      one that was made before the HBV genome was detectable by PCR. However, it was
      determined that transfusion was not responsible in many cases for HBV infection
      after transfusion.

PMID- 11452156
TI  - Allogeneic blood transfusion and postoperative duration of mechanical
      ventilation.
AB  - BACKGROUND: In patients having open heart surgery, allogeneic blood transfusion
      (ABT) may be related to an enhanced inflammatory response and impaired pulmonary
      function, resulting in the need for prolonged mechanical ventilation. STUDY
      DESIGN AND METHODS: The records of 416 consecutive patients undergoing coronary
      artery bypass graft surgery at Massachusetts General Hospital were reviewed.
      Possible predictors and the number of days of postoperative ventilation, as well
      as the number of RBC units transfused and the length of their storage, were
      recorded. The association between mechanical ventilation after the day of
      operation and the number of RBC units transfused was calculated by logistic
      regression analysis. RESULTS: The number of RBC units transfused, but not the
      length of their storage, differed (p<0.0001) among patients ventilated for 0, 1,
      2, 3, or 4 or more days after the day of operation. Patients taken off
      ventilation on the day of operation received (mean +/- SE) 2.01 +/- 0.14 RBC
      units; patients kept on ventilation for 4 or more days received 9.45 +/- 1.83
      units. After adjusting for the effects of 18 confounding factors, the number of
      RBC units transfused was not a significant predictor of ventilation past the day
      of operation. There was, however, a trend suggesting that the likelihood of such
      ventilation might increase by 26 percent per RBC unit transfused (p = 0.0628).
      CONCLUSIONS: Future studies of the outcomes of ABT should examine further the
      possibility of a relationship between the number of transfused RBCs and the
      likelihood of postoperative ventilation after the day of operation.

PMID- 11452157
TI  - Ceftizoxime-induced hemolysis secondary to combined drug adsorption and immune
      complex mechanisms.
AB  - BACKGROUND: Immune hemolytic anemia has been associated with the administration
      of various antibiotics, including cephalosporins. Presented here is a patient who
      developed severe acute hemolysis while receiving ceftizoxime (Ceftizox, Fujisawa
      USA), a third-generation cephalosporin. This is the fourth reported case of
      hemolysis in association with ceftizoxime. In the previous cases, ceftizoxime was
      shown to induce hemolysis by the immune-complex mechanism. However, in one of
      those reports, the concentration of drug used to treat the target RBCs in vitro
      may not have been optimal. CASE REPORT: The patient's antemortem blood samples
      were analyzed retrospectively for drug-dependent antibodies by the drug
      adsorption and immune-complex methods. Antibody class and titer were evaluated.
      RESULTS: The patient's sample agglutinated RBCs coated with ceftizoxime as well
      as uncoated RBCs in the presence of ceftizoxime. The antibodies to ceftizoxime
      were IgM and IgG. CONCLUSION: This is the first report on both the immune-complex
      and drug-adsorption mechanisms of ceftizoxime-induced hemolysis. The differential
      diagnosis of a falling Hct in a patient receiving antibiotics should include drug
      related hemolysis; once this diagnosis is considered, management includes the
      appropriate serologic workup, immediate cessation of the implicated drugs, and
      possible transfusion support.

PMID- 11452158
TI  - Inverse expression of P(k) and Luke blood group antigens on human RBCs.
AB  - BACKGROUND: Luke (LKE) is a high-frequency RBC antigen, related to the P blood
      group system. A LKE-negative phenotype is found in 1 to 2 percent of donors and
      may be associated with increased P(k). Because P(k) and similar glycolipids are
      receptors for shiga toxin on cell membranes, a LKE-negative phenotype could have
      implications for infections by Shigella dysenteriae and enterohemorrhagic
      Escherichia coli. STUDY DESIGN AND METHODS: Volunteer donors (n = 257) were
      serologically typed for LKE with a LKE MoAb, MC813-70. LKE-strong-positive, LKE
      weak-positive and LKE-negative RBCs were analyzed for P(k), P, LKE, and shiga
      toxin binding by immunofluorescence flow cytometry, high-performance thin-layer
      chromatography, scanning densitometry, and high-performance thin-layer
      chromatography immunostaining. RESULTS: Among Iowa donors, 78.6 percent were LKE
      strong-positive, 20.2 percent were LKE-weak-positive, and 1.2 percent were LKE
      negative. There was an inverse expression of P(k) and LKE on RBCs. P(k)
      expression was increased on LKE-negative RBCs and was associated with increased
      shiga toxin binding. A LKE-active glycolipid was identified in the ganglioside
      fraction of LKE-strong-positive RBCs. CONCLUSION: A LKE-negative phenotype is
      associated with increased expression of P(k) on RBCs. Differences in P(k) and LKE
      expression may play a role in host susceptibility to infection with S.
      dysenteriae and E. coli.

PMID- 11452159
TI  - Changes in immunologic properties of group A RBCs during treatment with an A
      degrading exo-alpha-N-acetylgalactosaminidase.
AB  - BACKGROUND: Blood group A RBCs theoretically can be converted to universal-donor
      group O cells by incubation with alpha-N-acetylgalactosaminidase (A-zyme). The
      purpose of this study was to compare the extent of A-zyme treatment required to
      abolish several immunologic responses of group B or O recipients to group A RBCs.
      STUDY DESIGN AND METHODS: A(1) RBCs were incubated for 2 hours at 37 degrees C in
      buffer alone (control) or with 0.1 to 5.0 units (U) of A-zyme per mL of packed
      cells. They were then tested for 1) immune adherence (% rosetting) and activation
      of monocytic cells (% erythrophagocytosis, TNFalpha production), 2) activation of
      immune hemolysis, and 3) hemagglutination with Dolichos biflorus lectin and
      pooled human anti-A serum. RESULTS: A 2-hour incubation with < or =5.0 U of A
      zyme per mL of packed cells abolished monocytic cell adherence and phagocytosis
      of group A(1) RBCs coated with IgG(3) A MoAb. Epitopes of A binding to IgG(3)
      anti-A A005 MoAb and BG-2 MoAb differed in A-zyme sensitivity. TNFalpha
      production in group B or O whole blood in response to the addition of A(1) cells
      varied, but it essentially was abolished when group A cells were treated with 0.1
      to 1.0 U of A-zyme per mL of packed cells. A epitopes mediating immune hemolysis
      and hemagglutination with D. biflorus lectin were also cleaved by <5 U of A-zyme
      per mL of packed cells. In contrast, hemagglutination with polyclonal anti-A
      typing serum was diminished by only 1 to 2 serial titer dilutions. CONCLUSION: A
      epitopes mediating immune hemolysis and immune adherence to and activation of
      monocytic cells are highly sensitive to A-zyme cleavage, as compared to those
      mediating hemagglutination with monoclonal and polyclonal anti-A.

PMID- 11452160
TI  - WBC-reduced platelet concentrates from pooled buffy coats in additive solution:
      an evaluation of in vitro and in vivo measures.
AB  - BACKGROUND: The use of a platelet additive solution (PAS-II, Baxter) may have
      benefits over plasma for storage of platelets. It was the aim of this study to
      develop a method to produce WBC-reduced platelet concentrates (PCs) in PAS-II
      with >240 x 10(9) platelets and <1 x 10(6) WBCs per unit, which can be stored for
      5 days at pH >6.8 and that will give sufficient platelet increments after
      transfusion: a 1-hour CCI of >7.5 and a 20-hour CCI of >2.5. STUDY DESIGN AND
      METHODS: PCs were made from five pooled buffy coats and 250 g of PAS-II. After
      centrifugation the PCs were WBC-reduced with a filter (Autostop BC, Pall
      Biomedical) and stored in a 1000-mL polyolefin container. CCIs were assessed in
      stable hemato-oncologic patients after 5-day old PCs were transfused. RESULTS:
      Routinely produced PCs contained a median of 310 x 10(9) platelets (n = 5,363)
      with 3.5 percent containing <240 x 10(9) platelets, in a median volume of 320 mL
      (n = 11,834). The median number of WBCs was <0.03 x 10(6) (n = 694). The WBC
      count exceeded 1 x 10(6) in three PCs, but it was always <5 x 10(6), giving 99
      percent confidence that more than 99.5 percent of the units will contain <1 x
      10(6) WBCs. The pH remained >6.8 on Day 8, provided the concentration was below
      1.1 x 10(9) platelets per mL (n = 32). After 28 transfusions in 28 patients, the
      1-hour CCI was 12.6 +/- 4.3 (mean +/- SD, with 2/28 CCIs <7.5) and the 20-hour
      CCI was 8.9 +/- 5.6 (with 4/28 CCIs <2.5). Limitations of this study include the
      absence of a control group of patients receiving platelets stored in plasma and
      of in vivo radiolabeled survival studies, but a comparison of these data with
      previously published data suggested that the in vivo survival of platelets stored
      in PAS-II is less than that of platelets stored in plasma. CONCLUSION: The WBC
      reduced PCs conformed to specifications. These WBC-reduced PCs could be stored at
      least 5 days with maintenance of pH, and they gave sufficient increments after
      transfusion to patients.

PMID- 11452161
TI  - The effect of two additive solutions on the postthaw storage of RBCs.
AB  - BACKGROUND: Sterile systems for freezing and for washing thawed blood will allow
      the storage of RBCs for more than 24 hours after removal of the cryoprotectant
      glycerol. This study assessed the effect of two ASs in maintaining deglycerolized
      RBCs. STUDY DESIGN AND METHODS: Twenty-four RBC units were stored for 6 days,
      pooled in groups of 4, realiquoted, sterilely glycerolized, and frozen. One month
      later, the units were thawed, sterilely deglycerolized by using an automated
      system (H215; Haemonetics), and stored for 5 weeks in either 100 or 200 mL of AS
      3 or an experimental AS (EAS-61). Sterile samples were taken weekly for chemical
      and morphometric analysis. RESULTS: The glycerolization and deglycerolization
      process produced highly comparable RBC units, but it caused a marked reduction of
      RBC pH, to about 6.4 at the beginning of storage. The addition of acidic AS-3
      further reduced the pH, which in turn reduced glucose consumption, lactate
      formation, and RBC ATP concentrations. Alkaline EAS-61 increased these measures.
      Hypotonic EAS-61 caused increased cell swelling and hemolysis, despite better RBC
      morphology. CONCLUSIONS: Automation of sterile glycerolization and
      deglycerolization with the H215 works well, but the solutions should be
      reformulated for extended postthaw storage. This would best be accomplished by
      raising the pH of the wash solutions by the addition of disodium phosphate or
      sodium bicarbonate or both, by using alkaline ASs, and by matching the osmolality
      of the wash solution and ASs.

PMID- 11452162
TI  - In vivo survival of apheresis RBCs, frozen with 40-percent (wt/vol) glycerol,
      deglycerolized in the ACP 215, and stored at 4 degrees C in AS-3 for up to 21
      days.
AB  - BACKGROUND: The FDA has approved the storage of frozen RBCs at -80 degrees C for
      10 years and the postwash storage at 4 degrees C for no more than 24 hours. The 4
      degrees C postwash storage period is limited to 24 hours, because the current
      deglycerolization systems are functionally open systems. STUDY DESIGN AND
      METHODS: Two units of RBCs were collected from each of 13 healthy male
      volunteers. The RBCs were collected in CP2D by the FDA-approved protocol for an
      automated apheresis device (MCS, LN8150, Haemonetics) and were stored at 4
      degrees C in AS-3 for 6 days. Using a single disposable glycerolization set in an
      automated, functionally closed system (ACP 215, Haemonetics) each unit was
      transferred to a 1000-mL PVC plastic bag and glycerolized to a concentration of
      40-percent (wt/vol) glycerol and frozen at -80 degrees C. A single disposable
      deglycerolization set in the ACP 215 was used to deglycerolize the 2 units from
      the same donor. The deglycerolized RBCs were stored at 4 degrees C in AS-3 for as
      long as 21 days. RESULTS: The mean +/- SD freeze-thaw-wash recovery value was
      89.4 +/- 3 percent. The residual hemolysis in the RBCs stored at 4 degrees C in
      AS-3 for 21 days after deglycerolization was 0.9 +/- 0.2 percent, and the units
      were negative for both aerobic and anaerobic bacteria. The mean Nageotte WBC
      count was 9 x 10(6) per unit. When the deglycerolized RBCs were given as an
      autologous transfusion after storage at 4 degrees C in AS-3 for the 7- to 18-day
      period, the mean +/- SD 24-hour posttransfusion survival was 77 +/- 7 percent,
      and the index of therapeutic effectiveness was 69 +/- 8 percent. CONCLUSION: Two
      units of human RBCs collected from a single donor by apheresis in the MCS using
      an LN8150 set can be glycerolized sequentially with a single disposable set and
      deglycerolized sequentially with another single disposable set in the ACP 215.
      The previously frozen RBCs stored in AS-3 for 7 to 18 days at 4 degrees C had
      acceptable hemolysis and an acceptable mean 24-hour posttransfusion survival
      value and index of therapeutic effectiveness.

PMID- 11452163
TI  - A multicenter study of in vitro and in vivo values in human RBCs frozen with 40
      percent (wt/vol) glycerol and stored after deglycerolization for 15 days at 4
      degrees C in AS-3: assessment of RBC processing in the ACP 215.
AB  - BACKGROUND: The FDA has approved the storage of frozen RBCs at -80 degrees C for
      10 years. After deglycerolization, the RBCs can be stored at 4 degrees C for no
      more than 24 hours, because open systems are currently being used. Five
      laboratories have been evaluating an automated, functionally closed system (ACP
      215, Haemonetics) for both the glycerolization and deglycerolization processes.
      STUDY DESIGN AND METHODS: Studies were performed at three military sites and two
      civilian sites. Each site performed in vitro testing of 20 units of RBCs. In
      addition, one military site and two civilian sites conducted autologous
      transfusion studies on ten units of previously frozen, deglycerolized RBCs that
      had been stored at 4 degrees C in AS-3 for 15 days. At one of the civilian sites,
      10 volunteers received autologous transfusions on two occasions in a randomized
      manner, once with previously frozen RBCs that had been stored at 4 degrees C in
      AS-3 for 15 days after deglycerolization and once with liquid-preserved RBCs that
      had been stored at 4 degrees C in AS-1 for 42 days. RESULTS: The mean +/- SD in
      vitro freeze-thaw-wash recovery value was 87 +/- 5 percent; the mean +/- SD
      supernatant osmolality on the day of deglycerolization was 297 +/- 5 mOsm per kg
      of H(2)O, and the mean +/- SD percentage of hemolysis after storage at 4 degrees
      C in AS-3 for 15 days was 0.60 +/- 0.2 percent. The paired data from the study of
      10 persons at the civilian site showed a mean +/- SD 24-hour posttransfusion
      survival of 76 +/- 6 percent for RBCs that had been stored at 4 degrees C for 15
      days after deglycerolization and 72 +/- 5 percent for RBCs stored at 4 degrees C
      in AS-1 for 42 days. At the three sites at which 24-hour posttransfusion survival
      values were measured by three double-label procedures, a mean +/- SD 24-hour
      posttransfusion survival of 77 +/- 9 percent was observed for 36 autologous
      transfusions to 12 females and 24 males of previously frozen RBCs that had been
      stored at 4 degrees C in AS-3 for 15 days after deglycerolization. CONCLUSION:
      The multicenter study showed the acceptable quality of RBCs that were
      glycerolized and deglycerolized in the automated ACP 215 instrument and stored in
      AS-3 at 4 degrees C for 15 days.

PMID- 11452164
TI  - Ex vivo evaluation of PBMNCs collected with a new cell separator.
AB  - BACKGROUND: This study reports on an evaluation of the ability of a cell
      separator (Amicus, Baxter Healthcare) and the integral MNC computer software
      program to collect a variety of MNC subsets. The collection efficiency (CE) of
      the Amicus for these MNC subsets was compared to that of another cell separator
      (CS-3000 Plus, Baxter). The collected MNCs were also assayed ex vivo to determine
      if these cells remained functional. STUDY DESIGN AND METHODS: Healthy volunteer
      blood donors were recruited to provide PBMNCs for the isolation of CD3+, CD4+,
      CD8+, CD19+, NK, and gammadelta+ cells and monocytes. Cells were collected with
      an Amicus (test arm; n = 16) or a CS-3000 Plus (control arm; n = 11) cell
      separator. Cells were counted on a flow cytometer and CEs were calculated. For
      functional studies, the Amicus-collected MNC data were compared to CS-3000 Plus
      historical data. Functional studies performed included surface antigen expression
      assays (CD8+), proliferation assays (CD4+ and CD8+ cells), NK cytotoxicity assays
      for K562 and HUVE cells, and E-selectin induction on endothelial cells through
      NK+ contact dependency. Dendritic cells (DCs) were generated from CD34+ cells
      collected on the Amicus, positively selected by the use of antibody-bound,
      magnetic bead technology, and then cultured ex vivo with a combination of growth
      factors to generate the DCs. RESULTS: CEs were higher on the Amicus than on the
      CS-3000 Plus for CD3+ (68 vs. 54%), CD4+ (70 vs. 56%), CD8+ (68 vs. 52%), and
      CD19+ (60 vs. 48%) cells (p<0.05). For the two separators, CEs were equivalent
      for monocytes, NK+, and gammadelta+ cells. The Amicus separator collected
      significantly fewer platelets than did the CS-3000 Plus (p<0.00001). CD4+, CD8+,
      and NK cells proliferated normally. NK cells appropriately stimulated E-selectin
      expression on endothelial cells. Culture-generated DCs obtained by using Amicus
      collected CD34+ cells expressed appropriate cell surface markers. CONCLUSION: The
      Amicus separator is acceptable for the collection of PBMNC subsets. The device
      collects CD3+, CD4+, CD8+, and CD19+ T- and B-cell subsets with greater
      efficiency and collects MNCs with significantly fewer contaminating platelets
      than does the CS-3000 Plus. Cells collected on the Amicus are suitable for use in
      a variety of research and clinical immunobiologic studies.

PMID- 11452165
TI  - Effect of prophylactic transfusion of stored RBCs on oxygen reserve in response
      to acute isovolemic hemorrhage in a rodent model.
AB  - BACKGROUND: The storage of RBCs results in a time-related decline in 2,3 DPG that
      may reduce the ability to unload oxygen (O(2)) to tissue. The objective of this
      study was to compare the effect that transfusion of stored 2,3 DPG-depleted rat
      blood (7 days in CPDA-1) had on the O(2) reserve in conscious rats, with that of
      the transfusion of fresh blood (<2-hour storage). STUDY DESIGN AND METHODS:
      Anemic rats (Hb, 80 g/L) received either fresh packed RBCs or stored RBCs to
      raise Hb levels to 140 g per L. They then underwent isovolemic hemorrhage
      mimicking surgical blood loss to the point of O(2) supply dependency (OSD).
      Critical O(2) delivery (DO(2)crit), Hb concentration, and O(2) extraction at OSD
      were measured in a metabolic chamber. RESULTS: After transfusion, RBC DPG
      decreased by 50 percent in the stored-blood group, and the p50 value decreased by
      5 mmHg (32.1 +/- 2.5 mmHg vs. 37.5 +/- 3.0). DO(2)crit was similar in the two
      groups (fresh blood: 2.79 +/- 0.44 mL/min x g(-1); stored blood, 2.99 +/- 0.76
      mL/min x g(-1)). The critical Hb concentration at DO(2)crit was higher in the
      stored-blood group (44 +/- 4 g/L) than in the fresh-blood group (38 +/- 5 g/L);
      the cardiac index and O(2) extraction ratio in the two groups were not different.
      Under conditions of severe normovolemic anemia in rats, depletion of DPG and a
      decrease in p50 had only minor effects on the O(2) reserve. At OSD, under these
      conditions, O(2) consumption is not limited by diffusion. CONCLUSION: The
      physiologic impact of DPG depletion in transfused stored blood on oxygen
      availability in normal rats appears to be small and may be clinically
      inconsequential.

PMID- 11452166
TI  - Role of oral versus IV iron supplementation in the erythropoietic response to
      rHuEPO: a randomized, placebo-controlled trial.
AB  - BACKGROUND: Preoperative treatment with rHuEPO (epoetin alfa: EPREX, Janssen
      Cilag; or PROCRIT, Ortho Biotech) in conjunction with iron supplementation
      increases the erythropoietic response in elective orthopedic surgery patients,
      but it is not known whether the magnitude of this response is dependent on the
      route of iron administration. STUDY DESIGN AND METHODS: Non-iron-deficient
      patients undergoing elective orthopedic surgery (N = 110) with baseline Hb > or
      =10 to < or =13 g per dL were randomly assigned to receive either epoetin alfa
      (600 IU/kg) plus IV iron (n = 29) or oral iron (n = 29) or placebo plus IV iron
      (n = 25) or oral iron (n = 27) in this 14-day study. RBC production, Hb, Hct,
      reticulocytes, iron status, and adverse events were monitored throughout the
      study. RESULTS: Epoetin alfa treatment plus either oral or IV iron
      supplementation significantly increased total RBC production, Hb, Hct, and
      reticulocytes over the values seen with the respective placebo treatments (p =
      0.0001). There were no differences between the epoetin alfa treatment groups.
      Placebo treatment plus oral or IV iron supplementation was not associated with
      increases in hematologic values. There were no differences in the incidence of
      adverse events among the treatment groups. CONCLUSION: There was a comparable
      erythropoietic response to epoetin alfa, irrespective of the route of iron
      administration. The route of iron administration, therefore, does not modulate
      the erythropoietic response to epoetin alfa in patients who are not iron
      deficient. Safety and convenience benefits may be gained by adopting oral iron
      supplementation in this patient subset.

PMID- 11452167
TI  - Is it time for blood banking to take off?

PMID- 11452168
TI  - The first photograph of blood transfusion.

PMID- 11452169
TI  - Duffy blood group phenotypes and genotypes in Chinese.

PMID- 11452170
TI  - DAL: a new partial RHD phenotype.

PMID- 11452171
TI  - Postural renal transplant obstruction: a case report and review of the
      literature.
AB  - A 48-year-old woman underwent cadaveric renal transplantation for end-stage renal
      failure secondary to polycystic kidney disease. Nine months after
      transplantation, intermittent renal dysfunction and severe graft hydronephrosis
      developed despite the presence of a ureteric stent. A Tc-99m MAG3 scan performed
      with the patient standing showed complete transplant obstruction. Rapid tracer
      clearance with progressive bladder filling was present when the patient was
      imaged in the supine position. Ureteric obstruction is the most common urologic
      complication of renal transplantation. However, postural ureteric obstruction has
      been described only rarely. This case indicates that posture may affect ureteric
      patency and highlights this potential pitfall in the evaluation of intermittent
      graft dysfunction by diuretic renography.

PMID- 11452172
TI  - Bone marrow biopsy and bone scan to detect skeletal metastases.
AB  - This study correlates the findings of bone marrow biopsy with those of bone scan
      in patients with common cancers and highlights the comparable sensitivities of
      the two methods at the authors' institution. The results show that bone
      scintigraphy may be slightly more sensitive than bone marrow examination for the
      detection of carcinomatous metastases. This experience suggests that institutions
      should devise clinical pathways based on their testing sensitivities and patient
      characteristics. These considerations will ultimately result in better and more
      cost-effective treatment of these patients.

PMID- 11452173
TI  - Scintigraphic evaluation of pamidronate and corticosteroid therapy in a patient
      with progressive diaphyseal dysplasia (Camurati-Engelmann disease).
AB  - A 27-year-old woman with progressive diaphyseal dysplasia (Camurati-Engelmann
      disease) received pamidronate and corticosteroid therapy for bone pain. During
      therapy, disease activity was assessed serially using bone scintigraphy with Tc
      99m HMDP. With pamidronate administration, the bone pain became worse and
      diaphyseal uptake of Tc-99m HMDP increased, whereas corticosteroid administration
      improved the bone pain and reduced the diaphyseal uptake. In this case,
      pamidronate and corticosteroid produced different effects. Bone scintigraphy
      allowed an objective assessment of the response to these treatments, accurately
      reflecting clinical symptoms.

PMID- 11452174
TI  - Comparison of In-111 octreotide and Tc-99m (V) DMSA scintigraphy in the detection
      of medullary thyroid tumor foci in patients with elevated levels of tumor markers
      after surgery.
AB  - PURPOSE: In this retrospective study, the authors evaluated the utility of In-111
      octreotide (OctreoScan) and Tc-99m (V) DMSA scintigraphy for the localization of
      recurrent metastatic tumor foci in patients with medullary thyroid cancer (MTC)
      and compared the findings with those of conventional radiologic imaging methods.
      METHODS: The scintigraphic images were compared with computed tomography (CT) and
      magnetic resonance imaging (MRI) and ultrasonography (US) in 14 patients (8 men,
      6 women; age range, 22 to 74 years) with elevated calcitonin and carcinoembryonic
      antigen levels after total thyroidectomy. All scintigraphic image findings were
      evaluated qualitatively as mild uptake (+) and moderate to marked uptake (++).
      RESULTS: In-111 octreotide may be superior to Tc-99m (V) DMSA for the detection
      of tumor foci of patients with MTC on a patient basis (78.5% versus 57.1%) and on
      a lesion basis (44.1% versus 30.2%). The sensitivity rate for In-111 octreotide
      (78.5%) was also similar to that of CT and MRI on a patient basis. Conversely,
      the combined use of Tc-99m (V) DMSA and In-111 octreotide revealed the best
      sensitivity rate (85.7%) on a patient basis, whereas the combined use of CT and
      MRI showed the best sensitivity rate (81.3%) on a lesion basis. CONCLUSIONS:
      These findings suggest that In-111 octreotide is superior to Tc-99m (V) DMSA and
      has a similar sensitivity rate to CT and MRI for the diagnosis of recurrent or
      metastatic MTC. Although the combined use of In-111 octreotide and Tc-99m (V)
      DMSA was most sensitive, the combined use of CT and MRI with radionuclide imaging
      methods may better detect more metastatic tumor foci.

PMID- 11452175
TI  - Elevated F-18 FDG uptake in laryngeal muscles mimicking thyroid cancer
      metastases.
AB  - Fluorine-18 fluorodeoxyglucose (F-18 FDG) has been used to evaluate early-stage
      larynx cancer and metastases of thyroid cancer. However, elevated F-18 FDG uptake
      in laryngeal muscles may lead to misinterpretation. In this report, three
      patients with thyroid cancer are described who had thyroid surgery 2 months to 1
      year before F-18 FDG positron emission tomographic imaging. Various degrees of
      moderate to intense uptake were observed in their laryngeal regions. In one
      patient, this was caused by laryngeal muscle uptake. To determine the origin of
      the increased muscle uptake in the other two patients, the authors analyzed the
      position and shape of the foci of high uptake in light of the patients' clinical
      histories and other imaging results.

PMID- 11452176
TI  - F-18 FDG uptake in a patient with psoriatic arthritis: imaging correlation with
      patient symptoms.
AB  - The authors describe a patient with psoriatic arthritis in whom an increased
      level of F-18 fluorodeoxyglucose (F-18 FDG) uptake was seen in the joints of the
      hands. The areas of increased activity correlated well with the regions of
      symptoms reported by the patient. This case illustrates the potential use of F-18
      FDG positron emission tomography to quantitatively assess the degree of arthritis
      activity.

PMID- 11452177
TI  - Does motion analysis in postexercise gated sestamibi SPECT reflect rest left
      ventricular motion even in severe coronary artery disease?
AB  - PURPOSE: Evidence has suggested that postexercise gated Tc-99m sestamibi SPECT
      (GSPECT) provides combined information about resting wall motion and exercise
      perfusion. No data have been published about possible differences in wall motion
      analysis between postexercise and resting GSPECT. METHODS: Fifty patients
      underwent postexercise (symptom-limited bicycle stress) and rest GSPECT and
      cardiac catheterization with contrast ventriculography. In 35 patients,
      additional rest planar Tc-99m RBC radionuclide ventriculography (RNV) was
      performed. Four observers independently performed left ventricular ejection
      fraction (LVEF) calculations and visual analysis of regional wall motion (graded
      in four stages) for all studies. RESULTS: The LVEF calculations in GSPECT
      revealed a statistically significant difference between postexercise (45.8 +/-
      15.7%) and rest (48.0 +/- 16.1%; P < 0.05) determination. Postrest GSPECT LVEF
      showed a better correlation with LVEF determination performed with contrast
      ventriculography and RNV than did postexercise GSPECT LVEF. The reduced
      postexercise wall motion could be shown in segments with exercise-induced
      ischemia and in those with normal regional perfusion but not in segments with
      irreversibly abnormal perfusion. CONCLUSIONS: Postexercise GSPECT provides
      reliable information regarding global wall motion even in severe coronary artery
      disease, but regional wall motion is underestimated compared with rest GSPECT,
      because of an imprecise surface detection algorithm in ischemic wall segments and
      possibly postexercise stunning in severe coronary artery disease.

PMID- 11452178
TI  - Abnormality of the myocardial sympathetic nervous system in a patient with Becker
      muscular dystrophy detected with iodine-123 metaiodobenzylguanidine scintigraphy.
AB  - PURPOSE: This study was performed to determine whether I-123
      metaiodobenzylguanidine (MIBG) scintigraphy can depict myocardial sympathetic
      nerve abnormalities in Becker muscular dystrophy. MATERIALS AND METHODS: A 34
      year-old man with Becker muscular dystrophy underwent Tl-201 and I-123 MIBG
      scintigraphy sequentially before and 4 months after the beginning of oral
      administration of enalapril maleate, an angiotensin-converting enzyme inhibitor.
      RESULTS: Before and during treatment, stress Tl-201 scintigraphy revealed
      nonreversible myocardial perfusion defects in the anterior, inferoposterior, and
      apical walls, and I-123 MIBG scintigraphy depicted a region with decreased
      sympathetic nerve function or innervation. Before treatment, the I-123 MIBG heart
      count- mediastinum count (H:M) ratio was 2.1 and the washout rate was 21% on
      delayed images obtained 4 hours after the injection of I-123 MIBG, indicating
      hyperactivity of the sympathetic nervous system in the myocardium. During
      treatment, the H:M ratio was 3.0 and the washout rate was 15%. CONCLUSION: With I
      123 MIBG scintigraphy it is possible to evaluate an abnormality of the myocardial
      sympathetic nervous system and the efficacy of administration of an angiotensin
      converting enzyme inhibitor in this disease.

PMID- 11452179
TI  - Apthoid stomatitis caused by vasculitis: focus detection and follow-up by whole
      body FDG positron emission tomography.

PMID- 11452180
TI  - Neural tuberculosis detected by F-18 FDG positron emission tomography.

PMID- 11452181
TI  - Severe tibial stress injury.

PMID- 11452182
TI  - Adductor insertion avulsion syndrome.

PMID- 11452183
TI  - Ga-67 imaging in a patient with polymyalgia rheumatica.

PMID- 11452184
TI  - Asymmetric limb uptake on Ga-67 citrate scintigraphy.

PMID- 11452185
TI  - Tc-99m MIBI SPECT correlated with magnetic resonance imaging for cardiac
      evaluation of a patient with congenitally corrected transposition of the great
      arteries (L-TGA).

PMID- 11452186
TI  - Hydatid cyst of the interventricular septum: an unusual cause of a fixed
      myocardial perfusion defect.

PMID- 11452187
TI  - Azygos lobe: findings on lung scintigraphy in a patient with pulmonary embolism.

PMID- 11452188
TI  - Unilateral ventilation--perfusion mismatch on pulmonary scintigraphy caused by
      anomalous origin of a pulmonary artery from the innominate artery.

PMID- 11452189
TI  - Ventilation-perfusion lung scan and helical computed tomographic findings in a
      patient with Behcet's disease.

PMID- 11452190
TI  - Detection of choriocarcinoma in the lung by FDG positron emission tomography.

PMID- 11452191
TI  - Urinary leak after intravenous urography: Tc-99m MAG3 scintigraphy and potential
      pitfalls.

PMID- 11452192
TI  - Lupus mesenteric vasculitis detected by Ga-67 scan.

PMID- 11452193
TI  - Intense skeletal lesions in a patient with primary hyperparathyroid disease.

PMID- 11452194
TI  - A case of postictal cortical blindness detected by brain perfusion SPECT.

PMID- 11452195
TI  - Moderate T1-201 chloride uptake in cerebral infarction.

PMID- 11452196
TI  - High extracerebral soft tissue activity on Tc-99m ethyl cysteinate dimer brain
      SPECT.

PMID- 11452197
TI  - Ga-67 scan in the diagnosis and monitoring of Ludwig's angina.

PMID- 11452198
TI  - Anesthesia for operative endoscopy.
AB  - Developments in both instruments and techniques have led to an increasing
      popularity of endoscopic surgery during the last two decades. Even though there
      are numerous advantages to using endoscopic surgery, life threatening surgical
      and anesthetic complications still exist. Precautions must be taken to cope with
      the potential complications. Anesthetic technique must provide optimal surgical
      conditions and lead to early recovery of the patient. Monitorization must allow
      safety of the patient during these potentially hazardous procedures. Both the
      anesthesiologist and the surgeon must be thoroughly aware of the potential
      complications of the procedure. This review discusses the physiological
      alterations occurring during operative endoscopy, the principles of anesthetic
      management and complications related both to surgery and to anesthesia
      techniques.

PMID- 11452199
TI  - Female sterilization: an update.
AB  - Female sterilization is the most popular form of birth control in the world. It
      is performed laparoscopically or through a minilap, depending on the timing
      (postpartum) and where the patient lives. It is a safe and efficacious procedure
      with few complications that can be performed under local or general anaesthesia.
      The techniques presently in use are all adequate and the choice should evolve
      from a discussion between the doctor and the patient.

PMID- 11452200
TI  - Current practical application of office endoscopy.
AB  - Outpatient hysteroscopy has shown good correlation of findings compared with
      inpatient hysteroscopy, but one limitation is pain and discomfort in some women,
      and vasovagal reaction. Various forms of local anaesthesia have been evaluated in
      the past year, with controversial results, and a narrow 3.5 mm sheath
      hysteroscope has been introduced. Transvaginal hydrolaparoscopy as an outpatient
      procedure has been further investigated.

PMID- 11452201
TI  - The cystic adnexal mass: patient selection, surgical techniques and long-term
      follow-up.
AB  - The continuous change in the treatment and management of ovarian tumours is an
      excellent example of the changes that have occurred in gynaecological
      laparoscopic surgery. This paper evaluates the management of the adnexal mass in
      2001. Second, it reviews ovarian tumours treated at the Department of Obstetrics
      and Gynaecology, University of Kiel, between January 1997 and December 1998, and
      the place of laparoscopy in the management of these lesions. Third, the review
      attempts to give an insight into the long-term follow-up of patients treated
      laparoscopically for the removal of ovarian cysts. Finally, a retrospective
      survey is given of the clinical pathology and prognostic features of adnexal
      masses operated on during pregnancy. With regard to long-term follow-up, no
      difference was found between laparoscopic or laparotomic treatment of ovarian
      tumours.

PMID- 11452202
TI  - Methods of tissue extraction in advanced laparoscopy.
AB  - Advances in laparoscopic surgery have revolved not only around new methods of
      tissue excision and repair, but also around specimen extraction. At the center of
      these recent advances is the need to be cost-effective and safe. Two particularly
      important advances in laparoscopic tissue extraction are use of electronic power
      morcellators, to cut up and remove large masses, and specimen bags to remove the
      extracted tissue safely. Although morcellators offer tremendous time savings, and
      can actually reduce the risk of hernia formation because fascia need not be torn
      or stretched, the use of power morcellators is not without concern. The sharp
      rotating blade can damage normal organs. Furthermore, one must watch closely so
      that morcellated specimens are not inadvertently misplaced. Specimen bags are
      also important, both in malignant and in benign conditions. Ultimately, the
      problem is spillage of tissue, whether it be cancer cells or products of
      conception. Although some specimen bags are equipped with self-opening devices,
      the largest bags must be opened manually.

PMID- 11452203
TI  - Cost effective management of heavy uterine bleeding: ablative methods versus
      hysterectomy.
AB  - The treatment of menorrhagia in the twentieth century changed after 1960 with the
      introduction of hormonal therapy as well as an array of laboratory, imaging and
      minimal access tests for more accurate diagnosis. Since 1981, hysteroscopy has
      been used for diagnosis as well as the control of thermoablative treatments of
      bleeding non-malignant endometrium, including laser, electrocoagulation and
      electroresection. The success rates, complications, intermediate range outcome
      and cost comparisons with hysterectomy favor hysteroscopic methods. But the long
      term data on both hysteroscopic ablation and hysterectomy are not yet complete.
      In an effort to simplify techniques, reduce costs, and reduce complications, a
      variety of non-hysteroscopic methods and devices have appeared. Only two balloon
      devices have satisfactory success data as well as sufficient field experience to
      provide some degree of reliability regarding complications, which appear to be
      very low. Most of the devices have had clinical trials, which suggest equivalence
      to hysteroscopic endometrial ablation, but the determination of clinical safety
      requires at least several thousand cases. However, the levels of effectiveness
      for most of these devices make them candidates for commercial use. Hysterectomy
      may move from a primary surgical treatment of menorrhagia to a second-line
      treatment after ablation, particularly if some of the non-hysteroscopic methods
      become well accepted. If they are found to be safe, the costs and ease of use for
      the gynecologist and patient will make them attractive as a first-line surgical
      option. Hysterectomy, whether abdominal, vaginal, or laparoscopic will then be
      applied to ablation failures or non-candidates. This has the potential to change
      gynecological training and practice significantly in the future.

PMID- 11452204
TI  - Laparoscopic management of urinary incontinence, ureteric and bladder injuries.
AB  - The present review focuses on the most recently published English language
      literature, and addresses results and complications associated with the
      laparoscopic approach to urinary incontinence, anterior vaginal wall prolapse,
      and lower urinary tract injury. Laparoscopic Burch procedures continue to show
      equal efficacy, but lower morbidity as compared with conventional open
      techniques. Lower urinary tract injuries may also be managed effectively using
      the same techniques as those employed in open procedures. Laparoscopy continues
      to be considered a mode of surgical access, and is effective in treating urinary
      incontinence, anterior vaginal wall prolapse, and lower urinary tract injuries.

PMID- 11452205
TI  - Hemorrhage in obstetrics and gynecology.
AB  - Hemorrhage has always been a significant potential complication in the field of
      obstetrics and gynecology. Throughout the years, a variety of medical and
      surgical modalities aimed at controlling uterine hemorrhage have been developed.
      Most recently, these have focused on attempting to decrease the morbidity
      associated with obstetric and gynecologic hemorrhage. Specifically, the aim of
      recent developments has been to reduce the need for laparotomy and increase the
      likelihood of uterine preservation (and thus the preservation of fertility). The
      present review addresses the use of such interventions in a sequential manner for
      attaining hemostasis.

PMID- 11452206
TI  - Complications and litigation in gynecologic endoscopy.
AB  - Most medical malpractice lawsuits that involve gynecologic endoscopy and
      laparoscopy result from either improper prevention, inadequate recognition, or
      delayed intervention. Continuing recognition of this will prevent many and
      mitigate most such cases. We can learn much from the events and rapid progress of
      the past decade. Although most laparoscopic improvements have been technical and
      instrument driven, a basic understanding of anatomy, physiology, and diagnostics
      remains essential to high-quality patient care and risk reduction.

PMID- 11452207
TI  - Resident training and endoscopic hospital privileging.
AB  - Laparoscopic techniques were originally confined to female sterilization. As both
      instrumentation and methodology improved, gynecological endoscopy was applied to
      more complex processes, including salpingostomy or salpingectomy for ectopic
      pregnancy, and ovarian cystectomy or oophorectomy for benign conditions. Now, the
      laparoscopic treatment of adhesions, endometriosis and hysterectomy is almost
      commonplace. More sophisticated endoscopic procedures include the management of
      pelvic floor disease, incontinence and malignancies. However, at least two
      problems have become readily apparent: (i) there is often limited basic
      laparoscopic and hysteroscopic teaching during residency and fellowship training;
      and (ii) there is no standard by which to privilege or train physicians who may
      not have had any significant endoscopic training during residency. In this
      article we describe current learning theories and identify goals and specific
      objectives for residents in implementing a successful training program. We also
      discuss the mechanisms by which to privilege attending staff for gynecological
      procedures and the important clinical outcomes that can be improved. Finally, we
      raise concerns about creating algorithms by which to renew clinical privileges in
      endoscopic procedures.

PMID- 11452209
TI  - Why is it important to be insulin sensitive?

PMID- 11452210
TI  - [The insulin sensitivity concept].
AB  - Insulin resistance was already suspected in the thirties from clinical
      observations in diabetic patients, then better appreciated in the early sixties
      with the development of insulin radioimmunoassay, and finally confirmed in the
      last 20 years by using various sophisticated methods able to quantify insulin
      action. First demonstrated in obese and/or type 2 diabetic patients, the
      diminution of insulin sensitivity may in fact concern a much larger population.
      The concept of insulin sensitivity gained a considerable importance when Reaven,
      in 1988, emphasized the role of insulin resistance in different human diseases.
      The metabolic syndrome or syndrome X is characterized by the association of
      various cardiovascular risk factors (among which impaired glucose tolerance,
      arterial hypertension and dyslipidaemias), all closely linked to insulin
      resistance which is indeed the core of the syndrome. Even if insulin action
      signalling appears to be rather complex and the mechanisms leading to insulin
      resistance still largely unknown, it is essential to develop pharmacological or
      non pharmacological strategies to improve insulin sensitivity for treating
      insulin-resistant individuals. Such an approach should allow not only to provide
      a better blood glucose control in patients with type 2 diabetes, but also to
      improve the cardiovascular prognosis of numerous patients, with or without
      diabetes mellitus, who have the metabolic syndrome.

PMID- 11452211
TI  - [How to measure insulin sensitivity in clinical practice?].
AB  - Insulin resistance is common and cluster with glucose intolerance, dyslipidaemia
      and high blood pressure,. in type 2 diabetes mellitus it play a key role in the
      occurence of hyperglycemia. The importance of the insulin-resistant phenotype for
      the assessment of cardiovascular risk and response to intervention is
      increasingly being recognized. Therefore there is a need for accurate,
      reproducible and simple methods for measuring insulin resistance in vivo. The
      euglycemic hyperinsulinemic clamp is currently the best available standard
      technique but is not suitable for clinical practice. Thus, numerous index for
      insulin resistance estimation from fasting or post-load OGTT glycemia and
      insulinemia have been proposed. Although their simplicity is an obvious
      advantage, their application is subject to numerous limitations. The choice of
      the method to evaluate insulin sensitivity thus depend on objectives and
      available means. For clinical research, euglycemic clamp is the gold standard. In
      the case of epidemiologic studies, validated models like HOMA model are suitable.
      Finally in clinical practice, for type 2 diabetic patients, evaluation of insulin
      resistance should be made from clinical and biological context eventually
      associated with an estimation of respectives roles of insulinopenia and insulin
      resistance with a validated index like the HOMA model.

PMID- 11452212
TI  - [Fat distribution and metabolism].
AB  - It is well known that adipose tissue distribution is an important factor involved
      in the etiology of type 2 diabetes and cardiovascular diseases. Adipose tissue
      distribution is obviously different between men and women, men being prone to
      accumulate their excess of energy in the abdominal region, more specifically in
      the intra-abdominal depot (visceral) whereas women show a selective deposition of
      adipose tissue in the gluteo-femoral region. Several studies have demonstrated an
      association between age and adipose tissue distribution and a selective
      deposition of visceral adipose tissue has been reported with age, in both men and
      women. In this regard, the menopause transition also appears to be a factor
      associated with an accelerated accumulation of abdominal adipose tissue. This
      increase in visceral adipose tissue has been suggested to play a significant role
      in the etiology of metabolic complications increasing the risk of type 2 diabetes
      and cardiovascular diseases. However, a selective mobilization of visceral
      adipose tissue in response to a weight loss program has been noted among
      viscerally obese patients, this reduction in visceral adipose tissue being
      associated with improvements in the lipoprotein-lipid profile and insulin
      sensitivity. Thus, the distribution of adipose tissue is an important factor to
      take into account in the evaluation of the patient. Furthermore, the amount of
      abdominal adipose tissue should also be considered as an important therapeutic
      target for the optimal management of cardiovascular disease risk.

PMID- 11452213
TI  - [Insulin sensitivity and ethnic groups].
AB  - Epidemiological surveys show a large variation of type 2 diabetes (DT2)
      prevalence from one country to another, suggesting ethnic discrepancies in
      insulin sensitivity. Many data seem to confirm this hypothesis. We will show them
      while concentrating on data provided by surveys performed in French-speaking
      countries. The mechanisms of the ethnic differences in insulin sensitivity are
      unclear and further insights are needed. More than genetic factors, environmental
      factors appear to be involved in the occurence of insulin resistance and DT2. The
      epidemic nature of obesity and subsequent DT2 in the world urges health
      authorities in each country to raise campaigns to promote changes in life style
      and nutritional habits before the announced pandemy of DT2 becomes reality.

PMID- 11452214
TI  - [Insulin sensitiviy and lipids].
AB  - Insulin plays a central role in regulation of lipid metabolism, with different
      sites of action. In the adipose tissue, insulin inhibits lipolysis via an
      inhibition of the lipase, leading to reduce the flux of free fatty acids into the
      circulation. Insulin inhibits the VLDL production by the liver. Insulin is a
      potent activator of the lipoprotein lipase, promoting the catabolism of
      triglyceride-rich lipoproteins (Chylomicrons, VLDL). insulin promotes the
      clearance of LDL. Indeed, insulin stimulates apoB/E receptor (LDL-receptor)
      activity and enhances LDL degradation via the LDL-receptor pathway. Insulin also
      plays an important role in HDL metabolism since it activates LCAT activity, it
      reduces PLTP activity and modulates the hepatic triglyceride lipase activity.
      Because of the key role of insulin in lipid metabolism, we can easily understand
      that all diseases with impaired insulin action, such as insulin resistance or
      diabetes mellitus, will be characterized by important lipid abnormalities, which
      are important factors responsible for the increased cardiovascular risk in the
      patients.

PMID- 11452215
TI  - [Insulin sensitivity, blood pressure and cardiovascular diseases].
AB  - Essential hypertension is one of the main components of the insulin resistance
      syndrome. Blood pressure levels are especially critical for the cardiovascular
      prognosis of patients with diabetes. However, whether the relationship between
      blood pressure levels and insulin sensitivity is causal, or just an association,
      remains debatable. In this study, this relationship is explored through the data
      of currently available clinical trials.

PMID- 11452216
TI  - [Insulin sensitivity and stress].
AB  - Metabolic adaptation is part of the response to stress and participate to produce
      a favorable state for cure. Carbohydrate metabolism is profoundly altered with an
      increase in basal cellular glucose uptake and utilization and in endogenous
      glucose production; insulin sensitivity is decreased. Glucose tolerance is
      altered and hyperglycemia develops. This state of hyperglycemia is most obviously
      directed to satisfy the increased need of the injured organs and of the
      inflammatory cells. The role of the cytokines in association to the stress
      hormones is important to these metabolic adaptations. This article reviews the
      main features of glucose homeostasis and the potential mechanisms leading to
      stress induced insulin resistance.

PMID- 11452217
TI  - [Insulin sensitivity and polycystic ovarian syndrome].
AB  - Insulinresistance, commonly associated with polycystic ovarian syndrome (PCOS),
      raises many unresolved debates about its prevalence, mechanism and true
      pathological role. Low insulin sensibility may have multiple origins among them
      genetic molecular defects in pathways of cellular insulin effects. A weight gain
      and android distribution of fat mass may reveal or increase insulin resistance
      and hyperinsulinemia. The preexisting unbalanced ovarian steroidogenesis
      secondary to abnormalities in gene coding for enzymes of P450C17 alpha might be
      the necessary support facilitating the stimulatory effect of hyperinsulinemia or
      other factors (LH, IGF1) on ovarian androgens. In practice, the phycisian has to
      know how to evaluate and to treat insulin resistance in view of its implication
      in dysovulation and, later on, metabolic and cardiovascular risks. Nutritional
      education and regular physical exercice are the necessary approaches. The
      efficacy and indications of metformin and thiazolidinediones have to be further
      evaluated.

PMID- 11452218
TI  - [Insulin resistance: why is it important to treat?].
AB  - The ability of insulin to stimulate muscle glucose disposal and inhibit adipose
      tissue lipolysis is impaired in patients with type 2 diabetes. The progression
      from normal glucose tolerance and/or impaired glucose tolerance to type 2
      diabetes only occurs when insulin secretory function declines to a degree that
      circulating insulin concentrations are no longer able to overcome muscle and
      adipose tissue insulin resistance. Although, ambient plasma insulin
      concentrations are not sufficiently high to maintain euglycaemia in patients with
      type 2 diabetes, absolute plasma insulin concentrations in these individuals are
      as high, if not higher, than in nondiabetic subjects. Since the plasma
      concentrations of insulin, or free fatty acids (FFAs), or both, are elevated in
      patients with type 2 diabetes secondary to muscle and adipose tissue insulin
      resistance, hypertriglyceridaemia is common in these individuals. Improvement in
      glycaemic control with insulin or insulin secretagogues is achieved by raising
      plasma insulin concentrations to a level high enough to overcome the insulin
      resistance. This is not the case with thiazolidinediones (TZDs): glycaemic
      control is associated with lower plasma insulin concentration. Compounds that
      improve insulin sensitivity and lead to lower glucose and insulin concentrations
      may have unique clinical benefit in the treatment of patients with type 2
      diabetes.

PMID- 11452219
TI  - [Physical exercise and insulin sensitivity].
AB  - Physical exercise is known to be essential in the treatment of type 2 diabetes.
      An increased glucose uptake is evidenced during acute muscular exercise, over the
      post-exercise period, and following physical training. In this paper, we review
      metabolic and molecular aspects of physical exercise. We emphasize on the non
      insulin dependent glucose transport induced by muscular contraction, which
      involves AMP-activated protein kinase. The discovery of this pathway is likely to
      open new therapeutic targets for type 2 diabetes.

PMID- 11452220
TI  - [Macronutrients, fat mass, fatty acid flux and insulin sensitivity].
AB  - Obesity and visceral or upper body fat distribution, have a major impact on
      insulin sensitivity. There is strong evidence to suggest that free fatty acids
      (FFA) contribute to the pathogenesis of insulin resistance and the metabolic
      syndrome. Increased FFA release from adipose tissue or failure of FFA using
      tissues to remove them normally, lead to increased triglycerides (TG) and FFA
      fluxes. Increased delivery of FFA to muscle reduces muscle glucose uptake and
      utilisation by substrate competition or direct inhibition of glucose transport.
      Insulin resistance has been correlated with the size of intramuscular TG store.
      Intracellular TG have been involved in beta cell failure the so called
      lipotoxicity phenomena. The rate of FFA to the liver is a major determinant of
      hepatic TG secretion. So the regulation of FFA distribution between FFA using
      tissues and the partition of FFA between storage and oxidation could be involved
      in the developpment of insulin resistance. The dietary macronutrients could play
      a role in nutrient partitioning but their role in the etiology of insulin
      resistance is poorly understood due to a paucity of credible intervention studies
      in humans. However deleterious effects of saturated fatty acids on insulin action
      and the beneficial effects of polyunsaturated fatty acids (PUFAs) could be
      suspected from animal studies, and from epidemiological or clinical studies in
      humans. A very high intake of sucrose or fructose could be deleterious but low
      glycemic index foods, and fibers could have protective effects. Weight loss can
      induce marked improvement in insulin resistance, but weight maintenance is also
      required to keep long term good metabolic results.

PMID- 11452221
TI  - [Mechanisms of action of thiazolidinediones].
AB  - The recent discovery and marketing of a new class of antidiabetic drug improving
      insulin sensitivity, the thiazolidinediones (TZD), has opened interesting
      therapeutic perspectives. Those molecules correct hyperglycemia and
      hyperinsulinemia in several animal models of NIDDM. Clinical studies in human
      have confirmed that TZD lowered postprandial and postabsorptive glycemia and
      insulinemia. Glucose clamp studies have clearly shown an improvement of insulin
      induced glucose utilization (in skeletal muscle). In contrast, the inhibition of
      glucose production in response to insulin was much less reproducible. TZD have
      also been used with success to treat insulin resistance in non-diabetic obeses,
      in glucose-intolerant prediabetic subjects and in patients with polycystic ovary
      syndrome (pcos). Nevertheless, TZD appears less efficient in human than in animal
      models. TZD bind to an isoform of a nuclear receptor, the PPARgamma (Peroxisome
      Proliferator Activated Receptor). PPAR gamma is a transcription factor which,
      after heterodimerization with the retinoid receptor (RXR), bind to specific
      response elements of a number of target genes and control their transcription.
      There is an excellent correlation between the hypoglycemic effects of TZD in vivo
      and their affinity for PPARgamma in vitro, but the site of action and the
      molecular mechanism of TZD still remain poorly known. In human, skeletal muscles
      are responsible for more than 80% of glucose uptake in response to insulin.
      Unfortunately, skeletal muscles contain limited amounts of PPAR gamma. How TZD
      with the principal site of action being adipose tissue, can improve glucose
      metabolism in skeletal muscle? One possibility is the following Another
      possibility is that chronic treatment with TZD induces PPAR gamma expression in
      skeletal muscles. Finally, TZD could have a direct effect on skeletal muscles,
      independently of PPARgamma.

PMID- 11452222
TI  - [Thiazolidinediones: clinical data and perspectives].
AB  - This brief review realizes a synthesis of the main clinical studies of the three
      thiazolidinediones (TZDs) which have been launched elsewhere, troglitazone,
      rosiglitazone and pioglitazone. At optimal dose, the three molecules have a
      similar effect, although slightly weaker for the first, on the fasting plasma
      glucose and HbA1c levels. They exhibit identical activity, or even higher for
      troglitazone, in combination with sulfonylureas, metformine and insulin. On the
      contrary, the three TZDs seem to differentiate according to their effects on
      lipid metabolism. While rosiglitazone only moderately and inconstantly reduces
      plasma triglycerides, troglitazone and pioglitazone decreases them by 15 to 25%.
      LDL-cholesterol levels are almost unaffected by pioglitazone while they increase
      by 6 to 8% with troglitazone and by more than 10% with rosiglitazone. On the
      other hand, HDL-cholesterol strongly increases with rosiglitazone and
      pioglitazone and only slightly on troglitazone. Besides these metabolic effects,
      TZDs have several properties which could be of therapeutical interest,
      particularly a possible beta cell protective effect. Except for the severe
      problems of hepatotoxicity which appear specific to troglitazone and have led to
      its withdrawal, TZDs are well tolerated. They share as major undesirable effects
      a risk of peripheral oedema, of anemia due to plasma volume expansion and of
      weight gain due to the development of subcutaneous adipose tissue. Until now, the
      European Product licence of rosiglitazone and pioglitazone is limited to the
      combination with metformin in case of failure of a monotherapy with metformin in
      obese type 2 diabetic patients and to the combination with a sulphonylurea only
      in case of intolerance or contra-indication to metformin in type 2 diabetics
      insufficiently controlled by sulphonylurea therapy at maximal tolerated dose.
      These indications will probably be enlarged to earlier treatments when long term
      study results will be available.

PMID- 11452224
TI  - Editorial.

PMID- 11452223
TI  - [Type 2 diabetes mellitus: Which place for thiazolidinediones in the therapeutic
      strategy?].
AB  - Several new pharmacological agents have recently been developed to optimise the
      management of type 2 diabetes mellitus. The aim of this article is to briefly
      review the new therapeutic class: thiazolidinediones (TZD), acting as these
      insulin sensitizer and to suggest a logical use of these drugs in the guidelines
      proposed by the french recommendations for the treatment of type 2 diabetic
      subjects. These agents are now introduced in Europe, only in combination with
      metformin or sulfonylureas (or glinides). Moreover, some preliminary data
      indicate that these agents could delay the decrease of insulin secretion by the
      beta pancreatic cells and could reduce other cardiovascular risk factors often
      associated with type 2 diabetes: hypertension and lipid abnormalities, by
      reducing blood pressure, triglycerides and increasing HDL cholesterol. These new
      drugs bring some hope in the treatment of type 2 diabetic patients in combination
      with the previous oral anti-diabetic drugs which have recently demonstrated
      (UKPDS) their ability to prevent or to reduce complications due to diabetes.
      However the frequency of adverse events must be evaluated in a large use, beyond
      phase II and III, after the withdrawal of the first TZD introduced on the market
      (troglitazone).

PMID- 11452225
TI  - From the Art Director's Desk.

PMID- 11452226
TI  - Negative immunoregulatory effects of noradrenaline through alpha2-adrenoceptor
      activation.
AB  - BACKGROUND: There are some reports that catecholamines and beta-adrenoceptor
      agonists may suppress some immune functions. OBJECTIVES: The present study was
      carried out in order to examine the effects of noradrenaline (10-5 M, 10-6 M and
      10-7 M), yohimbine (10-5 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor
      antagonist, and clonidine (105 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor
      agonist, on the stimulated production of interferon-gamma (IFNgamma), a pro
      inflammatory cytokine, and interleukin-10 (IL-10), an immuno-inhibitory cytokine.
      DESIGN: We measured the in vitro production of IFNgamma and IL-10 by stimulated,
      diluted whole blood of 16 normal volunteers. The IFNgamma/IL-10 production ratio
      was computed since this ratio reflects the pro- versus anti-inflammatory capacity
      of the cultured whole blood. RESULTS: We found that 1) noradrenaline, 10-5 M, 10
      6 M, and 10-7 M, significantly suppressed the production of IFNgamma and that
      noradrenaline, 10-5 M, significantly enhanced the production of IL-10. Clonidine,
      10-5 M and 10-7 M, significantly suppressed the production of IFNgamma.
      Noradrenaline, 10-5 M and 10-6 M, and clonidine, 10-5 M, significantly suppressed
      the IFNgamma/IL-10 production ratio. There were no significant effects of
      yohimbine on IFNgamma or IL-10 production. CONCLUSIONS: 1) noradrenaline has
      significant negative immunoregulatory effects in humans through enhancing the
      production of IL-10 and suppressing that of IFNgamma; and 2) the suppression of
      the production of IFNgamma is in part related to alpha2-adrenoceptor activation.

PMID- 11452227
TI  - Leptin modulates the corticotropin-releasing hormone (CRH) action on progesterone
      release from cultured rat granulosa cells.
AB  - OBJECTIVES: Corticotropin-releasing hormone (CRH) and leptin (LEP) are two
      neuropeptides involved in the regulation of food intake, energy homeostasis and
      stress response. These neuropeptides play an important role in the regulation of
      the hypothalamo-pituitary-gonadal (HPG) axis, too. It is known that leptin can
      affect the synthesis and release of CRH in the hypothalamus. There is no
      information about interactions between CRH and leptin directly in gonads. The aim
      of this study was to evaluate the effects of leptin and CRH on progesterone (P4)
      release from cultured rat granulosa cells obtained from mature rats in diestrus.
      METHODS: Granulosa cell cultures were maintained with CRH, LEP, CRH + LEP and CRH
      antagonist in varying concentrations. P4 supernatant concentrations were
      determined by RIA method. RESULTS: CRH stimulated P4 release, CRH-antagonist had
      no effect on P4 release alone but inhibited the CRH-stimulated P4 release, and
      the effect of leptin depended on concentration and on time of incubation.
      CONCLUSION: Our results show that leptin, beside its own influence, may effect on
      ovarian steroidogenesis through its interaction with effects of CRH activity.
      This is a new additional link between the stress response, body weight and
      reproductive functions.

PMID- 11452228
TI  - An integrative approach to the study of human behavior. (Poster accepted for the
      International Conference of Psychology "Psychology After The Year 2000" at the
      University of Haifa, Israel, June 12-14, 2000).
AB  - The human behavior is a fundamental phenomenon in contemporary sciences in the
      widest sense of the word. The wide range of world problems such as wars,
      criminality, social depravation, famine, different catastrophes as Tjernobyl up
      to the pandemic AIDS, etc. are transferable into one common denominator: the
      failure of man in his behavior. Adequate understanding of all behavioral
      mechanisms and their failures is condition sine qua non for the most important
      task-the prediction of actual behavior resulting from different bio-psycho-socio
      cultural sources. The authors express presumption about the essential importance
      of three basic postulates (I-III) in every kind of behavioral research: (I) Human
      life is an indivisible continuum from its very beginning (especially vulnerable)
      over adulthood (inclusive reproduction) until death. The prenatal stages of life
      are integral and very sensitive periods of human ontogenesis. Every discontinuity
      in this development can lead to physical, mental and social disfunctions in both
      prenatal and postnatal life. (II) Motivation is a basic inner drive generating
      the actual human behavior. All its five components should be taken into
      consideration: 1. Qualitative (the kind of motivational state: alimentary,
      sexual, territorial, etc.) 2. Quantitative (the intensity of motivational state,
      "arousal"). 3. Inner structure of each motivational state (into partial
      motivational states with specific sensitivity to external stimulation). 4.
      Synthetic (causal and functional aspects of actual motivation). 5. Hierarchy of
      motivational states (self-preservation of the individual is probably on the top
      of such a hypothetical hierarchical structure). (III) Both previous postulates
      demand the integrative approach to the study of human behavior and refers to
      three basic sources of behavior: 1. Function of the CNS. 2. Function of the
      endocrine system. 3.Variability of external conditions (including all kinds of
      behavioral stimulation).

PMID- 11452229
TI  - LAUDATIO to Professor Marian JUTISZ, outstanding scientist, great humanist and
      patriot, on his 80th Anniversary.

PMID- 11452230
TI  - Melatonin suppresses autoxidation and hydrogen peroxide-induced lipid
      peroxidation in monkey brain homogenate.
AB  - OBJECTIVES: Melatonin, the major secretory product of the pineal gland, is known
      as an effective antioxidant and neuroprotector. Its neuroprotective actions and
      mechanisms have been documented in a variety of rodent brain models. However,
      little is known of melatonin's antioxidative capacity in the brain of primates.
      Herein, we investigated whether melatonin would suppress autoxidation and
      exogenous hydrogen peroxide-induced lipid peroxidation in monkey cerebral
      cortical homogenates. MATERIALS AND METHODS: The monkey brain was dissected
      during routine autopsy and immediately frozen at -80 degrees C until the
      experiment. A sample of cerebral cortex (50 mg) was homogenized in 1 ml ice cold
      phosphate buffer (20 mM, pH 7.4) at 0-4 degrees C. Four different treatments of
      cerebral cortical homogenates were performed: 1) homogenates incubated in a water
      bath at different temperatures (4 degrees C, 25 degrees C or 37 degrees C,
      respectively) for two hours to induce autoxidation; 2) homogenates co-incubated
      with different concentrations of melatonin at 37 degrees C for 2 hours; 3)
      homogenates co-incubated with 1 mM vitamin C and different concentrations of
      hydrogen peroxide at 37 degrees C for 1 hour to induce membrane lipid
      peroxidation; 4) homogenates incubated with different concentrations of melatonin
      and 1 mM H2O2 plus 1 mM vitamin C. After incubation, homogenates were analyzed
      for products of lipid peroxidation (malondialdehyde and 4-hydroxy-alkenals).
      RESULTS: The levels of lipid peroxidation products significantly increased in
      monkey cerebral cortical homogenates as a consequence of autoxidation or after
      the addition of H2O2 plus vitamin C. Melatonin not only suppressed the increase
      in lipid peroxidation induced by H2O2 plus vitamin C but also inhibited lipid
      breakdown resulting from autoxidation. The concentrations of melatonin required
      to suppress lipid peroxidation resulting from autoxidation or induced by
      exogenous oxidants in monkey cerebral cortical homogenates were in the same dose
      range. CONCLUSION: The results show for the first time that melatonin functions
      as an antioxidant and neuroprotector in primate brain tissue as was observed
      previously in rodent brain. The data provide information supporting the use of
      melatonin in the treatment of neurodegenerative disorders that involve oxidative
      damage to brain lipids.

PMID- 11452231
TI  - Effect of immunization on nocturnal NAT activity in chicken pineal gland.
AB  - OBJECTIVES: The effect of a single immunization with sheep red blood cells (SRBC)
      on the nocturnal NAT activity in the pineal gland and serum anti-SRBC agglutinin
      titer was examined in the young, sexually immature ASTRA S chickens. METHODS: 3-,
      4-, and 5-week-old birds of both sexes, hatched in long (Spring) and short
      (Autumn) day, were housed from hatching in controlled light (L:D = 12:12) and
      temperature conditions. Quantity of produced 14C-labeled N-acetyltryptamine was
      used as a measure of the nocturnal NAT activity in the pineal gland. Serum anti
      SRBC agglutinins were determined by microhemagglutination test. RESULTS: In
      experimental conditions applied, a sexual dimorphism in both pineal gland
      function and immune system activity was observed. NAT activity was dependent on
      the season, sex and age of chickens examined and was modified by the single
      immunization with SRBC. CONCLUSION: Results obtained confirmed once again the
      existence of the reciprocal functional connection between the pineal gland and
      immune system in chickens and demonstrated that even in well controlled
      experimental conditions the influence of the seasonal factor(s) on immunity must
      be taken into consideration.

PMID- 11452233
TI  - Evidence for a neuroimmunomodulatory and a hematopoietic role of the Luschka's
      coccygeal body(3).
AB  - OBJECTIVES: In humans the glomus coccygeus was described in 1860 by Luschka. It
      is present at the coccyx tip and corresponds to a complex anastomosis between the
      median sacral artery and vein, and it is innervated by sympathetic fibers. In
      rats and mice it has been located in the tail ventral face. Its function is not
      known. According to our previous work, which demonstrated that hematopoiesis is
      under a noradrenergic control and based on the presence of epithelioid cells and
      sympathetic innervation, we assumed that the coccygeal gland might influence
      hematopoiesis via neuroendocrine or neural mechanisms. Therefore, the present
      study was undertaken to analyze the effect of glomus coccygeus on hematopoiesis.
      MATERIAL AND METHODS: Peripheral blood leukocyte and platelet concentrations as
      well as body temperature (BT) and body weight (BW), and norepinephrine (NE),
      adrenaline (A) and dopamine (DA) content in bone marrow of Luschkaectomized
      (LCGx), Sham LCGx operated (ShLCGx) and normal mice (Co) were investigated.
      RESULTS: We found that in LCGx vs. ShLCGx and Co, platelets and neutrophils
      increased while lymphocytes decreased. The effect of LCGx was significant from
      day 0 until day 65. Total leukocytes, monocytes, granulocytes, eosinophils and BT
      did not show any variation. Moreover, 22 days after the operation the amount of
      NE, A and DA seemed to be decreased in LCGx vs. ShLCGx while the difference was
      less evident between ShLCGx vs. Co. CONCLUSIONS: This study suggests for the
      first time a possible hematopoietic function and an immunomodulatory activity of
      the "Luschka's body" or Coccygeal body by a modulation of the sympathetic nervous
      system.

PMID- 11452232
TI  - Gestational diabetes as possible risk factor for Type I childhood-onset diabetes
      in the offspring.
AB  - Epidemiological, clinical, as well as experimental findings obtained during the
      past two decades in Germany suggest that gestational diabetes might be a
      predisposing factor for increased risk of Type I childhood-onset diabetes in the
      offspring, which could therefore be prevented-at least in part-by systematic
      diagnostic screening and correction of maternal hyperglycemia during pregnancy.

PMID- 11452234
TI  - Variation in cerebrospinal fluid levels of neuropeptide Y, cholecystokinin and
      substance P in patients with neurological disorders.
AB  - Neuropeptide Y, cholecystokinin (tetra- and octasulphated peptides) and substance
      P were measured in lumbar cerebrospinal fluid obtained from patients with various
      neurologic disorders such as Parkinson's disease, cerebrovascular disorders,
      multiple sclerosis, tuberculous meningitis and aseptic meningitis. These results
      are statistically compared with healthy results. The results accumulated showed
      that the data collected can provide the vital information necessary for designing
      drug therapy.

PMID- 11452235
TI  - CASE REPORT: Invasive fibrous thyroiditis (Riedel's disease) with signs of giant
      cell arteritis.
AB  - OBJECTIVES: The authors described a case of Riedel's thyroiditis, a relatively
      rare disease affecting the thyroid gland. RESULTS: A 38-year-old female was
      diagnosed with Riedel's thyroiditis by a frozen section examination during
      attempted surgery for the suspicion of malignancy. The histopathologic
      examination confirmed the diagnosis of Riedel's thyroiditis combined with signs
      of giant cell arteritis. After hemithyroidectomy, the patient had paresis of the
      recurrent laryngeal nerve for five days and signs of hypothyroidism and
      hypoparathyroidism for three months after surgery. The level of thyroid
      peroxidase antibodies titer was higher. The patient had no compression symptoms,
      no signs of systemic immunopathology, and no signs of extracervical fibrosis. She
      was put on prednison 5 mg daily. CONCLUSIONS: Riedel's thyroiditis can be looked
      upon as a cervical fibrosis of unknown etiology affecting the thyroid. In our
      case it was combined with signs of giant cell arteritis.

PMID- 11452236
TI  - Efficacy of bromocriptine in the treatment of metastatic breast cancer- and
      prostate cancer-related hyperprolactinemia.
AB  - OBJECTIVE: Hyperprolactinemia is a frequent evidence occurring in both metastatic
      breast cancer and prostate cancer, and it has been proven to be associated with
      poor prognosis and reduced efficacy of the anticancer therapies. Therefore, the
      pharmacological control of cancer-related hyperprolactinemia could improve the
      prognosis of advanced breast and prostate carcinomas. Unfortunately, at present
      it is still controversial which may be the treatment of cancer-related
      hyperprolactinemia, which could depend at least in part on a direct autocrine
      production by cancer cells themselves. The present study was performed to
      evaluate the acute effects of the long-acting dopaminergic agonist bromocriptine
      on cancer-related hyperprolactinemia. METHODS: The study included 10 women
      affected by metastatic breast cancer and 10 men with metastatic prostate cancer,
      showing persistent hyperprolactinemia. Venous blood samples were collected before
      bromocriptine, and 2, 4, 10 and 24 hours after bromocriptine administration (2.5
      mg orally) serum levels of PRL were measured with the double antibody RIA method.
      RESULTS: Bromocriptine induced a normalization of PRL levels in both groups of
      patients with breast and prostate cancers. Moreover, mean levels of PRL persisted
      significantly lower than those found before therapy during the whole 24-hour
      circadian period. DISCUSSION: This preliminary study shows that low-dose
      bromocriptine is sufficient to acutely normalize PRL secretion in both metastatic
      breast cancer and prostate carcinoma patients, irrespectively of the mechanisms
      involved in inducing cancer-related hyperprolactinemia. Therefore, low-dose
      bromocriptine could be recommended in association with the classical antitumor
      therapies in the treatment of metastatic breast cancer and prostate carcinoma
      patients showing cancer-related hyperprolactinemia, in an attempt to improve the
      efficacy of anticancer therapies themselves.

PMID- 11452237
TI  - Pharmacogenetics, pharmacogenomics, and pharmacobiology.

PMID- 11452238
TI  - Simple approach to predict the maximal effect elicited by a drug when plasma
      concentrations are not available or are dissociated from the effect, as
      illustrated with chondroitin sulfate data.

PMID- 11452239
TI  - Orally given melatonin may serve as a probe drug for cytochrome P450 1A2 activity
      in vivo: a pilot study.
AB  - BACKGROUND: Melatonin is a hormone that is metabolized by cytochrome P450 (CYP)
      1A2 to its main primary metabolite 6-hydroxymelatonin. We therefore evaluated the
      utility of oral melatonin as a marker of hepatic CYP1A2 activity. METHODS: Twenty
      five milligrams of melatonin was given at 9:30 am to 12 healthy Swedish
      volunteers, who had previously been phenotyped for CYP1A2 with caffeine.
      Melatonin and conjugated 6-hydroxymelatonin were analyzed by liquid
      chromatography-mass spectrometry in blood samples taken between 0.5 and 6.5 hours
      after drug intake. Serum concentrations of melatonin and conjugated 6
      hydroxymelatonin, or their ratio at different time points, and the apparent
      melatonin clearance were tested for correlation with caffeine clearance. RESULTS:
      We found a significant correlation between apparent clearance of melatonin and
      caffeine clearance with a Spearman rank correlation coefficient (Rs) of 0.75 (P
      =.005). The melatonin concentration 1.5 hours after administration also closely
      correlated with the caffeine clearance (Rs = -0.62; P =.03). Inclusion of
      conjugated 6-hydroxymelatonin gave no closer correlations. CONCLUSION: Melatonin
      might be developed as an alternative to caffeine as a probe drug for CYP1A2
      phenotyping.

PMID- 11452240
TI  - Red wine-cisapride interaction: comparison with grapefruit juice.
AB  - OBJECTIVES: Our objective was to compare the interactions of red wine and
      grapefruit juice with cisapride. METHODS: The oral pharmacokinetics of cisapride,
      its norcisapride metabolite, and electrocardiographic QTc interval were
      determined over a 24-hour period after administration of cisapride 10 mg with 250
      mL grapefruit juice, red wine (cabernet sauvignon), or water in a randomized 3
      way crossover study in 12 healthy men. RESULTS: The cisapride area under the
      concentration-time curve (AUC) and the maximum plasma drug concentration after
      single-dose administration (C(max)) with grapefruit juice were 151% (P <.01) and
      168% (P <.001), respectively, of those with water. The increase in cisapride AUC
      and C(max) was variable among individuals; however, cisapride AUC and C(max) were
      enhanced by the same proportion. The time to reach maximum concentration after
      drug administration (t(max)) and the apparent elimination half-life (t((1/2)) for
      cisapride and the pharmacokinetics of norcisapride were not altered.
      Norcisapride/cisapride ratios were reduced. Cisapride AUC and C(max) with red
      wine were 115% (difference not statistically significant) and 107% (difference
      not statistically significant), respectively, of those with water. The cisapride
      t(max) was slightly longer. Cisapride t((1/2)) and norcisapride pharmacokinetics
      were not different. The norcisapride/cisapride ratio at cisapride C(max) was
      lower. One subject had a doubling in cisapride AUC and C(max) and a decrease in
      norcisapride/cisapride ratios with red wine and also had the largest interaction
      with grapefruit juice. QTc interval was unchanged in all treatment groups and
      individuals. CONCLUSIONS: A single glass of grapefruit juice produced an
      individual-dependent variable increase in the systemic availability of cisapride
      by inhibition of intestinal cytochrome P450 3A4 (CYP3A4) activity. The identical
      volume of red wine caused only minor changes in cisapride pharmacokinetics
      despite some inhibition of CYP3A4 in most individuals. However, even this amount
      of red wine may cause a marked interaction similar to that for grapefruit juice
      in individuals with a preexisting high intestinal CYP3A4 content.

PMID- 11452241
TI  - Population pharmacokinetics of dapsone in children with human immunodeficiency
      virus infection.
AB  - BACKGROUND: Previous studies of dapsone pharmacokinetics in children have been
      too small to allow assessment of the relationships between dapsone
      pharmacokinetic parameters and patient characteristics or markers of efficacy and
      toxicity. METHODS: We used population analysis to estimate dapsone
      pharmacokinetic parameters in children participating in a phase I/II study of
      daily and weekly dapsone in children with human immunodeficiency virus (HIV)
      infection. With use of the program NONMEM and a 1-compartment open model, the
      influence of demographic and clinical characteristics on oral clearance (CL/F)
      and oral volume of distribution (V/F) were examined. Measures of drug exposure
      (area under the concentration-time curve [AUC] and predicted concentrations just
      before and 2 hours after administration) were estimated for each patient and
      correlated with markers of efficacy and toxicity. RESULTS: Sixty children (median
      age, 3 years; age range, 2 months to 12 years) contributed 412 dapsone
      concentrations collected after 175 study doses. Final parameter estimates were
      1.40 L/kg for V/F, 0.0283 L/kg/h for CL/F, and 2.66 for the absorption rate
      constant. Of the clinical characteristics evaluated, dapsone CL/F was
      significantly increased by 50% in children taking rifabutin, by 39% in black
      children, and by 38% in children younger than 2 years old. Although no
      significant correlations were found between any dapsone exposure parameter and
      markers of toxicity, increased AUC was associated with a decreased risk of
      Pneumocystis carinii pneumonia (PCP). CONCLUSION: Ethnicity, age, and concomitant
      rifabutin use were associated with dapsone CL/F, with more rapid clearance
      observed in black children, children younger than 2 years old, and children
      receiving rifabutin. Dapsone pharmacokinetic parameters were not associated with
      toxicity, but higher dapsone AUC was associated with decreased risk of PCP.
      Monitoring of serum dapsone levels may be needed for optimal management of
      dapsone for PCP prophylaxis in children.

PMID- 11452242
TI  - Levodopa pharmacokinetic-pharmacodynamic modeling and 6-[18F]levodopa positron
      emission tomography in patients with Parkinson's disease.
AB  - OBJECTIVE: Parameters of a pharmacokinetic-pharmacodynamic (PK-PD) model of
      levodopa have been claimed to reflect the magnitude of the dopaminergic deficit
      in patients with Parkinson's disease. The aim of this study was to correlate such
      parameters with positron emission tomography (PET) with levodopa tagged with 6
      fluorine 18, an established imaging method for striatal dopaminergic neurons.
      METHODS: Twenty-three patients in different disease stages (Hoehm and Yahr stage
      2.5-5 [Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality.
      Neurology 1967;4:427-42]; median duration, 12 years) were studied. PK-PD modeling
      followed a single oral dose of levodopa/benserazide. The sum score of the
      Columbia Rating Scale (CURSSigma) was used for clinical assessments. A
      nonparametric effect compartment approach assuming a sigmoidal E(max) model was
      applied to the PK-PD analysis of plasma levodopa concentrations and corresponding
      CURSSigma. Thereafter 6-[18F]levodopa PET was performed, and the influx rate
      constants (k(c)) for the putamen and the caudatus region were correlated with the
      median effective concentration (EC(50)) and the equilibrium half-life (T(eq)) of
      the PK-PD model. RESULTS: (1) A significant correlation was observed between PK
      PD parameters or with k(c) putamen as the dependent variable and the duration of
      the disease as the independent variable, which explains 33% of the variability of
      the EC(50), 42% of the variability of T(eq), and 36% of the variability of k(c).
      (2) Significant correlations were observed between k(c) and either EC(50) or
      T(eq), yielding the closest correlation for the putamen region (r = -0.47, P
      <.05; and r = 0.55, P <.01; respectively). CONCLUSIONS: Our findings show that
      key parameters of a PK-PD model of levodopa were in fairly close agreement with
      imaging of dopaminergic neurons by 6-[18F]levodopa PET. However, although PK-PD
      modeling of levodopa has been proven as a useful investigation of approaches
      aimed to restore dopaminergic deficits or to monitor disease progression, this
      modeling cannot serve as a pathomorphologic surrogate for the loss of striatal
      dopaminergic neurons.

PMID- 11452243
TI  - Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19.
AB  - OBJECTIVE: Our objective was to evaluate the relationship between the disposition
      of sertraline and the presence of the CYP2C19 gene and to define the contribution
      of cytochrome P450 2C19 (CYP2C19) to sertraline N-demethylation. METHODS: A
      single oral 100-mg dose of sertraline was administered to 6 subjects who were
      extensive metabolizers and 6 subjects who were poor metabolizers recruited from
      77 healthy Chinese volunteers whose genotypes were predetermined by polymerase
      chain reaction-based amplification, followed by restriction fragment length
      polymorphism analysis. Phenotypes were determined by use of the omeprazole
      metabolic rate. The plasma concentrations of sertraline and desmethylsertraline
      were determined by gas chromatography with electron-capture detection. RESULTS:
      Six poor metabolizers with m1 mutation had area under the plasma concentration
      versus time curve (AUC(0-infinity)) values (983.6 +/- 199.3 microg x h/L versus
      697.6 +/- 133.0 microg x h/L; P <.05) and terminal elimination half-life values
      of sertraline (35.5 +/- 5.6 hours versus 23.5 +/- 4.4 hours; P <.01) that were
      significantly higher than the values in 6 extensive metabolizers who were either
      homozygous or heterozygous for CYP2C19*1. The oral clearance of sertraline in
      poor metabolizers (105.3 +/- 19.4 L/h) was significantly lower than that of
      extensive metabolizers (148.4 +/- 28.6 L/h). The area under the concentration
      time curve from 0 to 144 hours and the maximum plasma concentration of
      desmethylsertraline in poor metabolizers were significantly lower than the values
      of extensive metabolizers (627.6 +/- 203.8 microg x h/L versus 972.1 +/- 270.3
      microg x h/L; P <.05; and 23.6 +/- 6.5 nmol/L versus 32.4 +/- 8.2 nmol/L; P <.01;
      respectively). CONCLUSIONS: The polymorphic CYP2C19 appears to be a major enzyme
      involved in the N-demethylation of sertraline, and both extensive and poor
      metabolizers had marked differences in the disposition of sertraline.

PMID- 11452244
TI  - Pharmacokinetics and pharmacodynamics of methadone enantiomers after a single
      oral dose of racemate.
AB  - BACKGROUND: The pharmacokinetics and dynamics of methadone are characterized by
      high interindividual variability. This study aimed to examine a number of factors
      that may contribute to this variability. METHODS: Eight healthy drug-free women
      were administered 0.2 mg/kg of R,S-methadone orally. The concentrations of
      methadone's enantiomers in plasma and urine were monitored for 96 hours. Vital
      signs, blood biochemical parameters, and pupillary diameter were monitored
      frequently during this period. Cytochrome P450 3A (CYP3A) activity and alpha1
      acid glycoprotein (alpha1-AGP) concentrations and phenotypes were determined.
      Pharmacokinetic and pharmacodynamic modeling was used to assess the influence of
      the above-mentioned covariables on methadone enantiomer disposition and actions.
      RESULTS: The pharmacokinetic profile of the active enantiomer of methadone, R 
      methadone, showed a relatively normal distribution with 38% to 90% of the
      interindividual variability in modeled pharmacokinetic parameters being explained
      by their individual variability in CYP3A activity, the cumulative amount of the
      main CYP3A4 metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine,
      excreted in the urine, the fraction unbound in plasma, and the alpha1-AGP
      orosomucoid 2 (ORM2) variant plasma concentration. S-Methadone showed an
      idiosyncratic distribution with largely unpredictable pharmacokinetics. Pupillary
      constriction response was highly variable between individuals. CONCLUSIONS: The
      disposition of the active enantiomer, R -methadone, can be predicted in part by
      CYP3A activity and protein binding to alpha1-AGP (ORM2), whereas S-methadone
      disposition is not well explained by the factors examined in this study. Central
      nervous system effects were difficult to interpret on the basis of plasma R
      methadone pharmacokinetics.

PMID- 11452245
TI  - The cytochrome P4503A4 inhibitor clarithromycin increases the plasma
      concentrations and effects of repaglinide.
AB  - OBJECTIVE: Our objective was to study the effects of the macrolide antibiotic
      clarithromycin on the pharmacokinetics and pharmacodynamics of repaglinide, a
      novel short-acting antidiabetic drug. METHODS: In a randomized, double-blind, 2
      phase crossover study, 9 healthy volunteers were treated for 4 days with 250 mg
      oral clarithromycin or placebo twice daily. On day 5 they received a single dose
      of 250 mg clarithromycin or placebo, and 1 hour later a single dose of 0.25 mg
      repaglinide was given orally. Plasma repaglinide, serum insulin, and blood
      glucose concentrations were measured up to 7 hours. RESULTS: Clarithromycin
      increased the mean total area under the concentration-time curve of repaglinide
      by 40% (P <.0001) and the peak plasma concentration by 67% (P <.005) compared
      with placebo. The mean elimination half-life of repaglinide was prolonged from
      1.4 to 1.7 hours (P <.05) by clarithromycin. Clarithromycin increased the mean
      incremental area under the concentration-time curve from 0 to 3 hours of serum
      insulin by 51% (P <.05) and the maximum increase in the serum insulin
      concentration by 61% (P <.01) compared with placebo. No statistically significant
      differences were found in the blood glucose concentrations between the placebo
      and clarithromycin phases. CONCLUSIONS: Even low doses of the cytochrome P4503A4
      (CYP3A4) inhibitor clarithromycin increase the plasma concentrations and effects
      of repaglinide. Concomitant use of clarithromycin or other potent inhibitors of
      CYP3A4 with repaglinide may enhance its blood glucose-lowering effect and
      increase the risk of hypoglycemia.

PMID- 11452246
TI  - Analgesic effects of peripherally administered opioids in clinical models of
      acute and chronic inflammation.
AB  - A series of double-blind, placebo-controlled clinical trials demonstrated that
      low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the
      intraligamentary space of a chronically inflamed hyperalgesic tooth produced a
      dose-related naloxone-reversible analgesia. This analgesic effect is mediated by
      a local mechanism in the inflamed tissue, because subcutaneous administration of
      a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast,
      submucosal administration of 1.2 mg morphine or 50 microg fentanyl to the site of
      extraction of an impacted third molar after the onset of acute pain failed to
      elicit an analgesic response despite demonstration of a sensitive bioassay. These
      data indicate that peripheral opioid analgesia can be evoked in a model of
      chronic, but not acute, inflammatory pain, suggesting a temporal dependent
      mechanism needed for the expression of peripheral opiate analgesia during
      inflammation in humans.

PMID- 11452247
TI  - Median effect analysis of efficacy versus adverse effects of immunosuppressants.
AB  - BACKGROUND: A rigorous model to describe concentration-effect relations-the
      median effect analysis-was applied to quantitate immunosuppressive versus adverse
      effects in human renal transplantation. METHODS: The median effect equation was
      used to analyze data collected from three clinical studies, including the two
      phase III blinded, placebo-controlled trials (n = 1295 patients) of sirolimus
      versus azathioprine or placebo treatment added to a cyclosporine (INN,
      ciclosporin)/prednisone regimen and a sirolimus/azathioprine/prednisone (in the
      absence of cyclosporine) phase II cohort (n = 41 patients). RESULTS: The clinical
      effects correlated with drug concentrations as expressed by the median effect
      equation. Sirolimus or cyclosporine alone permitted drug concentrations that were
      5-fold and 2.2-fold lower, respectively, to render 90% of patients rejection
      free, suggesting a synergistic interaction between the two drugs. Further, the
      sirolimus concentrations to render 50% of patients rejection-free were about 200
      fold and 60-fold less, respectively, than the concentration that caused 50% of
      patients to experience thrombocytopenia or hypertriglyceridemia. The correlation
      coefficient of the median effect analysis for the occurrence of
      hypercholesterolemia was more robust for sirolimus than for cyclosporine.
      Although the concentrations for 50% of patients rendered rejection-free versus
      50% affected by hypercholesterolemia were similar, a 7-fold difference was
      calculated between the concentrations at which 90% of patients were free of
      rejection versus patients who were affected by hypercholesterolemia. CONCLUSION:
      The median effect analysis proffers a useful tool to assess both drug
      interactions and the windows between therapeutic versus toxic effects of
      immunosuppressive agents. The current analysis suggests a synergistic interaction
      between sirolimus and cyclosporine.

PMID- 11452248
TI  - Analgesic efficacy of rectal versus oral acetaminophen in children after major
      craniofacial surgery.
AB  - BACKGROUND: Analgesic acetaminophen (INN, paracetamol) plasma concentrations
      after major surgery in neonates and infants have not yet been established in the
      literature. We therefore conducted a study in our intensive care unit. METHODS:
      Forty children, mean (standard deviation) age, 10.3 (2.3) months, received 20
      mg/kg acetaminophen either orally (n = 20) or rectally (n = 20) every 6 hours
      after a rectal loading dose (40 mg/kg) during elective craniofacial correction.
      Blood samples were taken 1 hour before and 2 hours after administration of
      acetaminophen maintenance doses; pain scores were obtained every 3 hours.
      RESULTS: Acetaminophen plasma concentrations were higher in patients receiving
      rectal acetaminophen (mean area under the concentration-time curve [AUC], 171.2
      mg x h/L) than in patients receiving oral acetaminophen (mean AUC, 111.9 mg x
      h/L). Pain scores were higher in patients receiving oral acetaminophen. However,
      after exclusion of the patients who vomited from the group receiving oral
      acetaminophen, acetaminophen plasma concentrations and pain scores did not differ
      between the groups. There was no relation between acetaminophen plasma
      concentrations and pain scores. Although 9 of all 40 patients (22.5%) did not
      reach the expected analgesic acetaminophen plasma concentrations of 10- to 20
      mg/L, <7.5% of the visual analog scale pain scores exceeded 4 cm, which was
      considered as a cutoff point. CONCLUSION: These are the first data showing that
      the analgesic acetaminophen plasma concentration after major surgery in this age
      group does not always reach the 10 to 20 mg/L level. These data also show that,
      after a rectal loading dose of 40 mg/kg has been given during surgery, the best
      way of administering acetaminophen after craniofacial surgery is the rectal
      route.

PMID- 11452249
TI  - Effects of oral administration of ibutamoren mesylate, a nonpeptide growth
      hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in
      growth hormone-deficient children.
AB  - Ibutamoren mesylate (MK-0677), an orally active nonpeptide growth hormone (GH)
      secretagogue, stimulates GH release through a pituitary and hypothalamic receptor
      that is different from the GH-releasing hormone receptor. We evaluated the safety
      and tolerability and the GH-insulin-like growth factor (IGF) responses to two
      dosages of oral ibutamoren mesylate given to children with GH deficiency for 7 to
      8 days. The patients, 18 prepubertal children (15 male, 3 female) with idiopathic
      GH deficiency, had a chronologic age of 10.6 +/- 0.8 years (mean +/- SD), bone
      age of 7.4 +/- 0.7 years, growth velocity < 10th percentile for age, height <
      10th percentile for age, and a maximum GH response of < or = 10 microg/L to two
      different GH stimulation tests. The children were assigned as follows to one of
      three treatment groups with ibutamoren mesylate: 0.2 mg/kg per day for 7 days
      (days 1-7 or 8-14) and matching placebo for the alternate 7 days (groups I and
      II, respectively) or 0.8 mg/kg per day for 7 days (days 8-14, group III). On day
      15 all patients received an 0.8-mg/kg dose of ibutamoren mesylate. Patients in
      groups I and II were studied first to assess safety at the low dose before
      advancement to the high dose. Hormonal profiles were evaluated on day -1
      (baseline) and day 15, and the results were expressed as the change from baseline
      within each group. After administration of ibutamoren mesylate 0.8 mg/kg for 8
      days (group III), the median increases (on day 15) from baseline were as follows:
      3.8 microg/L (range, 0 to 34.3) for serum GH peak concentration (P = .001), 4.3
      microg x h/L (range, 1.3 to 35.6) for the GH area under the concentration-time
      curve from time zero to 8 hours (AUC(0-8)) (P < .001), 12 microg/L (range, -4 to
      116) for serum IGF-I (P = .01), and 0.4 microg/L (range, -0.9 to 1.5) for serum
      IGF-binding protein 3 (IGFBP-3) (P = .01). There was no change in serum
      prolactin, glucose, triiodothyronine, thyroxine, thyrotropin, peak serum
      cortisol, and insulin concentrations or 24-hour urinary free cortisol after
      administration of 0.8 mg/kg per day of ibutamoren mesylate for 8 days. We
      conclude that short-term administration of ibutamoren mesylate can increase GH,
      IGF-I, and IGFBP-3 levels in some children with GH deficiency. Thus this compound
      is applicable for testing its effect on growth velocity.

PMID- 11452251
TI  - Bringing patient outcomes home.

PMID- 11452252
TI  - Outcomes management: an administrator's view.

PMID- 11452253
TI  - Protecting human subjects: informed consent revisited: part I.

PMID- 11452254
TI  - What functional outcomes and complications should be taught to the patient with
      ulcerative colitis or familial adenomatous polyposis who undergoes ileal pouch
      anal anastomosis?

PMID- 11452255
TI  - WOC practice in cyberspace: legal and ethical issues.
AB  - WOC nurses have the opportunity to extend their practice geographically by using
      electronic media, also called telehealth or "practicing in cyberspace."
      Currently, laws and regulations affecting this aspect of practice are in rapid
      flux. In addition, practicing electronically makes the ethical issues of choice,
      privacy, and confidentiality more acute. This article describes the current
      status of relevant legislation, discusses relevant ethical issues, and provides
      guidelines for WOC nurses who are considering the use of e-mail and video
      conferencing within their practice.

PMID- 11452256
TI  - A long-term study of patient outcomes with pelvic muscle re-education for urinary
      incontinence.
AB  - PURPOSE: The purpose of this study was to determine the level of continence,
      satisfaction, and compliance with a maintenance pelvic muscle exercise program 12
      months or more after discharge from a clinician-supervised pelvic floor muscle
      rehabilitation program. SETTING AND SUBJECTS: Forty-nine female patients
      diagnosed with stress, urge, and mixed etiology urinary incontinence were treated
      with pelvic muscle re-education and biofeedback. Treatment was performed in a
      urology clinic setting with sessions supervised by a registered nurse. METHODS: A
      retrospective chart review was performed for all female patients trained in
      pelvic muscle exercises from March 1997 through November 1997. Telephone
      interviews were conducted and questionnaires were administered to determine long
      term efficacy of and compliance with pelvic muscle exercises 13 to 20 months
      after treatment. RESULTS: Fifty-three percent of patients maintained their
      posttreatment level of continence, and 38% had improved when evaluated 13 to 20
      months following treatment (x macro = 16.6 months). Sixty-nine percent continued
      to perform pelvic muscle exercises once weekly or several times per week.
      CONCLUSIONS: Clinician-supervised pelvic floor muscle rehabilitation is effective
      in improving stress and urge incontinence in community-dwelling women with
      stress, urge, and mixed urinary incontinence. This effect is durable for a period
      of 16 months, and the majority of women continue to perform pelvic muscle
      exercises one or more times per week.

PMID- 11452257
TI  - The pouch acting as a mediator between "being a person with an ostomy" and "being
      a professional": analysis of a pedagogical strategy.
AB  - OBJECTIVE: This study analyzes the process of constructing and reconstructing the
      meanings of the concepts ostomy, ostomy patient, and the nurse's role in managing
      an ostomy after the experience of wearing a pouch. SUBJECTS AND SETTING: Thirty
      nurses who were students in the Enterostomal Therapy Nursing Education Program in
      1992 and 1993 participated in this study. All of the participants were female,
      ages 20 to 55 years, had graduated from nursing at least 6 years previously, and
      had been working at acute care hospital units or at outpatient care centers. The
      research was completed at the Enterostomal Therapy Nursing Education Program in
      the Nursing College of the University of Sao Paulo. METHODS: All participants
      wore a pouch and lived as an ostomy patient for a 24-hour period and then were
      interviewed about their experience. Two major themes were identified after
      analysis: "being a person with an ostomy" and "being a professional." RESULTS:
      The experience of wearing a pouch promoted changes in perceived role, self
      esteem, body image, sexuality, and social relations. These changes were sometimes
      perceived as stigmatization and sometimes as enhancing social support. The
      perceptions caused a crisis that provoked the use of coping and social defense
      mechanisms that ultimately altered the participants' perceptions of the meaning
      of "being a nurse." Prior to this learning experience, the participants'
      management of patients with ostomies was fragmented and marked by a dissociation
      among activity, thinking, and feeling. Before the experiences, participants
      defined their management of patients with ostomies as mostly technical, focusing
      on the ostomy and the pouch. Following the experience, participants proposed
      changes in practice designed to care for the whole human being, revealing an
      incorporation of the affective, symbolic, and relational dimensions critical to
      managing the care of patients with an ostomy. CONCLUSION: The results showed that
      having subjects wear a pouch as a pedagogic strategy was successful in directing
      the participants' thinking about new meanings concerning "being a professional,"
      resulting in some potential profound changes in the future nursing care of their
      patients.

PMID- 11452258
TI  - Adjuvant anabolic agents: a case report on the successful use of oxandrolone in
      an HIV-positive patient with chronic stasis ulceration.
AB  - Chronic venous stasis ulcers and HIV represent 2 prevalent disease processes in
      the urban wound care setting. To best serve our patients, it is important that
      the wound care team carefully consider the impact of comorbidities and consider
      use of nutritional interventions. In this article we report the use of the
      anabolic agent oxandrolone to successfully treat an HIV-positive man with stasis
      ulceration.

PMID- 11452259
TI  - Surgical and nonsurgical options for a patient with a retracted stoma and
      peristomal skin crease.

PMID- 11452261
TI  - Blessings of mixed neutrinos.

PMID- 11452260
TI  - Wound healing: biologic features and approaches to maximize healing trajectories.

PMID- 11452262
TI  - Los Alamos loses physics archive as preprint pioneer heads east.

PMID- 11452264
TI  - Imported stem cells deepen Germany's ethical divide.

PMID- 11452266
TI  - Europe plots comeback in neutron science.

PMID- 11452267
TI  - Gene screens for nuclear veterans.

PMID- 11452269
TI  - Utopian dream in tatters as Starlab crashes to Earth.

PMID- 11452270
TI  - Hong Kong seeks secrets of Chinese medicine.

PMID- 11452271
TI  - US blood ban underlines CJD fears.

PMID- 11452273
TI  - Which side are you on?

PMID- 11452274
TI  - Meet the Herod bug.

PMID- 11452275
TI  - Identifying dangers in an uncertain climate.

PMID- 11452276
TI  - Attention to bioweapons obscures the real threats.

PMID- 11452281
TI  - The Sirens' song.

PMID- 11452280
TI  - What are clones?

PMID- 11452282
TI  - Signs of galactic cannibalism.

PMID- 11452283
TI  - Biogeochemistry. The nitrogen fix.

PMID- 11452284
TI  - Apoptosis. DNA destroyers.

PMID- 11452285
TI  - High-energy physics. Neutrinos reveal split personalities.

PMID- 11452288
TI  - Quantum physics. Air juggling and other tricks.

PMID- 11452287
TI  - Evolutionary biology. Searching for speciation genes.

PMID- 11452289
TI  - Ecology. Price put on biodiversity.

PMID- 11452290
TI  - Planetary science. Climate change on Venus.

PMID- 11452292
TI  - Obituary. Wang Ying-lai (1907-2001).

PMID- 11452293
TI  - Surrogate mother for endangered Cupressus.

PMID- 11452294
TI  - Pathogen reservoirs. Chironomid egg masses and Vibrio cholerae.

PMID- 11452295
TI  - Carbon fixation. Photosynthesis in a marine diatom.

PMID- 11452297
TI  - Aerodynamics. Insects can halve wind-turbine power.

PMID- 11452299
TI  - Dopamine responses comply with basic assumptions of formal learning theory.
AB  - According to contemporary learning theories, the discrepancy, or error, between
      the actual and predicted reward determines whether learning occurs when a
      stimulus is paired with a reward. The role of prediction errors is directly
      demonstrated by the observation that learning is blocked when the stimulus is
      paired with a fully predicted reward. By using this blocking procedure, we show
      that the responses of dopamine neurons to conditioned stimuli was governed
      differentially by the occurrence of reward prediction errors rather than stimulus
      reward associations alone, as was the learning of behavioural reactions. Both
      behavioural and neuronal learning occurred predominantly when dopamine neurons
      registered a reward prediction error at the time of the reward. Our data indicate
      that the use of analytical tests derived from formal behavioural learning theory
      provides a powerful approach for studying the role of single neurons in learning.

PMID- 11452300
TI  - A giant stream of metal-rich stars in the halo of the galaxy M31.
AB  - Recent observations have revealed streams of gas and stars in the halo of the
      Milky Way that are the debris from interactions between our Galaxy and some of
      its dwarf companion galaxies; the Sagittarius dwarf galaxy and the Magellanic
      clouds. Analysis of the material has shown that much of the halo is made up of
      cannibalized satellite galaxies, and that dark matter is distributed nearly
      spherically in the Milky Way. It remains unclear, however, whether cannibalized
      substructures are as common in the haloes of galaxies as predicted by galaxy
      formation theory. Here we report the discovery of a giant stream of metal-rich
      stars within the halo of the nearest large galaxy, M31 (the Andromeda galaxy).
      The source of this stream could be the dwarf galaxies M32 and NGC205, which are
      close companions of M31 and which may have lost a substantial number of stars
      owing to tidal interactions. The results demonstrate that the epoch of galaxy
      building still continues, albeit at a modest rate, and that tidal streams may be
      a generic feature of galaxy haloes.

PMID- 11452301
TI  - Dynamical tunnelling of ultracold atoms.
AB  - The divergence of quantum and classical descriptions of particle motion is
      clearly apparent in quantum tunnelling between two regions of classically stable
      motion. An archetype of such non-classical motion is tunnelling through an energy
      barrier. In the 1980s, a new process, 'dynamical' tunnelling, was predicted,
      involving no potential energy barrier; however, a constant of the motion (other
      than energy) still forbids classically the quantum-allowed motion. This process
      should occur, for example, in periodically driven, nonlinear hamiltonian systems
      with one degree of freedom. Such systems may be chaotic, consisting of regions in
      phase space of stable, regular motion embedded in a sea of chaos. Previous
      studies predicted dynamical tunnelling between these stable regions. Here we
      observe dynamical tunnelling of ultracold atoms from a Bose-Einstein condensate
      in an amplitude-modulated optical standing wave. Atoms coherently tunnel back and
      forth between their initial state of oscillatory motion (corresponding to an
      island of regular motion) and the state oscillating 180 degrees out of phase with
      the initial state.

PMID- 11452302
TI  - Quantum interference of superfluid 3He.
AB  - Celebrated interference experiments have demonstrated the wave nature of light
      and electrons, quantum interference being the manifestation of wave-particle
      duality. More recently, double-path interference experiments have also
      demonstrated the quantum-wave nature of beams of neutrons, atoms and Bose
      Einstein condensates. In condensed matter systems, double-path quantum
      interference is observed in the d.c. superconducting quantum interference device
      (d.c. SQUID). Here we report a double-path quantum interference experiment
      involving a liquid: superfluid 3He. Using a geometry analogous to the
      superconducting d.c. SQUID, we control a quantum phase shift by using the
      rotation of the Earth, and find the classic interference pattern with periodicity
      determined by the 3He quantum of circulation.

PMID- 11452303
TI  - Coexistence of superconductivity and ferromagnetism in the d-band metal ZrZn2.
AB  - It has generally been believed that, within the context of the Bardeen-Cooper
      Schrieffer (BCS) theory of superconductivity, the conduction electrons in a metal
      cannot be both ferromagnetically ordered and superconducting. Even when the
      superconductivity has been interpreted as arising from magnetic mediation of the
      paired electrons, it was thought that the superconducting state occurs in the
      paramagnetic phase. Here we report the observation of superconductivity in the
      ferromagnetically ordered phase of the d-electron compound ZrZn2. The specific
      heat anomaly associated with the superconducting transition in this material
      appears to be absent, and the superconducting state is very sensitive to defects,
      occurring only in very pure samples. Under hydrostatic pressure superconductivity
      and ferromagnetism disappear at the same pressure, so the ferromagnetic state
      appears to be a prerequisite for superconductivity. When combined with the recent
      observation of superconductivity in UGe2 (ref. 4), our results suggest that
      metallic ferromagnets may universally become superconducting when the
      magnetization is small.

PMID- 11452304
TI  - A possible nitrogen crisis for Archaean life due to reduced nitrogen fixation by
      lightning.
AB  - Nitrogen is an essential element for life and is often the limiting nutrient for
      terrestrial ecosystems. As most nitrogen is locked in the kinetically stable
      form, N2, in the Earth's atmosphere, processes that can fix N2 into biologically
      available forms-such as nitrate and ammonia-control the supply of nitrogen for
      organisms. On the early Earth, nitrogen is thought to have been fixed
      abiotically, as nitric oxide formed during lightning discharge. The advent of
      biological nitrogen fixation suggests that at some point the demand for fixed
      nitrogen exceeded the supply from abiotic sources, but the timing and causes of
      the onset of biological nitrogen fixation remain unclear. Here we report an
      experimental simulation of nitrogen fixation by lightning over a range of Hadean
      (4.5-3.8 Gyr ago) and Archaean (3.8-2.5 Gyr ago) atmospheric compositions, from
      predominantly carbon dioxide to predominantly dinitrogen (but always without
      oxygen). We infer that, as atmospheric CO2 decreased over the Archaean period,
      the production of nitric oxide from lightning discharge decreased by two orders
      of magnitude until about 2.2 Gyr. After this time, the rise in oxygen (or
      methane) concentrations probably initiated other abiotic sources of nitrogen.
      Although the temporary reduction in nitric oxide production may have lasted for
      only 100 Myr or less, this was potentially long enough to cause an ecological
      crisis that triggered the development of biological nitrogen fixation.

PMID- 11452305
TI  - Annual monsoon rains recorded by Jurassic dunes.
AB  - Pangaea, the largest landmass in the Earth's history, was nearly bisected by the
      Equator during the late Palaeozoic and early Mesozoic eras. Modelling experiments
      and stratigraphic studies have suggested that the supercontinent generated a
      monsoonal atmospheric circulation that led to extreme seasonality, but direct
      evidence for annual rainfall periodicity has been lacking. In the Mesozoic era,
      about 190 million years ago, thick deposits of wind-blown sand accumulated in
      dunes of a vast, low-latitude desert at Pangaea's western margin. These deposits
      are now situated in the southwestern USA. Here we analyse slump masses in the
      annual depositional cycles within these deposits, which have been described for
      some outcrops of the Navajo Sandstone. Twenty-four slumps, which were generated
      by heavy rainfall, appear within one interval representing 36 years of dune
      migration. We interpret the positions of 20 of these masses to indicate slumping
      during summer monsoon rains, with the other four having been the result of winter
      storms. The slumped lee faces of these Jurassic dunes therefore represent a
      prehistoric record of yearly rain events.

PMID- 11452306
TI  - Morphological and ecological complexity in early eukaryotic ecosystems.
AB  - Molecular phylogeny and biogeochemistry indicate that eukaryotes differentiated
      early in Earth history. Sequence comparisons of small-subunit ribosomal RNA genes
      suggest a deep evolutionary divergence of Eukarya and Archaea; C27-C29 steranes
      (derived from sterols synthesized by eukaryotes) and strong depletion of 13C (a
      biogeochemical signature of methanogenic Archaea) in 2,700 Myr old kerogens
      independently place a minimum age on this split. Steranes, large spheroidal
      microfossils, and rare macrofossils of possible eukaryotic origin occur in
      Palaeoproterozoic rocks. Until now, however, evidence for morphological and
      taxonomic diversification within the domain has generally been restricted to very
      late Mesoproterozoic and Neoproterozoic successions. Here we show that the
      cytoskeletal and ecological prerequisites for eukaryotic diversification were
      already established in eukaryotic microorganisms fossilized nearly 1,500 Myr ago
      in shales of the early Mesoproterozoic Roper Group in northern Australia.

PMID- 11452307
TI  - The impact of ultraviolet radiation on the vertical distribution of zooplankton
      of the genus Daphnia.
AB  - The vertical migration of zooplankton into lower and darker water strata by day
      is generally explained by the avoidance of visually orienting predators, mainly
      fish; however, it is unclear why daily zooplankton migration has been maintained
      in fishless areas. In addition to predation, ultraviolet radiation-a hazardous
      factor for zooplankton in the surface layers of marine and freshwater
      environments-has been suspected as a possible cause of daytime downward
      migration. Here we test this hypothesis by studying several Daphnia species, both
      in a controlled laboratory system and under natural sunlight in an outdoor
      system. We selected Daphnia species that differed in their pigmentation as both
      melanin and carotenoids have been shown to protect Daphnia from ultraviolet
      light. All Daphnia species escaped into significantly deeper water layers under
      ultraviolet radiation. The extent to which the daphnids responded to this
      radiation was inversely linked to their pigmentation, which reduced ultraviolet
      transmission. These results suggest that ultraviolet avoidance is an additional
      factor in explaining daytime downward migration. Synergistic benefits might have
      shaped the evolution of this complex behaviour.

PMID- 11452308
TI  - Partitioning selection and complementarity in biodiversity experiments.
AB  - The impact of biodiversity loss on the functioning of ecosystems and their
      ability to provide ecological services has become a central issue in ecology.
      Several experiments have provided evidence that reduced species diversity may
      impair ecosystem processes such as plant biomass production. The interpretation
      of these experiments, however, has been controversial because two types of
      mechanism may operate in combination. In the 'selection effect', dominance by
      species with particular traits affects ecosystem processes. In the
      'complementarity effect', resource partitioning or positive interactions lead to
      increased total resource use. Here we present a new approach to separate the two
      effects on the basis of an additive partitioning analogous to the Price equation
      in evolutionary genetics. Applying this method to data from the pan-European
      BIODEPTH experiment reveals that the selection effect is zero on average and
      varies from negative to positive in different localities, depending on whether
      species with lower- or higher-than-average biomass dominate communities. In
      contrast, the complementarity effect is positive overall, supporting the
      hypothesis that plant diversity influences primary production in European
      grasslands through niche differentiation or facilitation.

PMID- 11452309
TI  - Cryptic evolution in a wild bird population.
AB  - Microevolution is expected to be commonplace, yet there are few thoroughly
      documented cases of microevolution in wild populations. In contrast, it is often
      observed that apparently heritable traits under strong and consistent directional
      selection fail to show the expected evolutionary response. One explanation
      proposed for this paradox is that a genetic response to selection may be masked
      by opposing changes in the environment. We used data from a 20-year study of
      collared flycatchers (Ficedula albicollis) to explore selection on, and evolution
      of, a heritable trait: relative body weight at fledging ('condition'). Despite
      consistent positive directional selection, on both the phenotypic and the
      additive genetic component (breeding values, estimated from an animal model) of
      condition, the mean phenotypic value of this trait in the population has
      declined, rather than increased, over time. Here we show that, despite this
      decline, the mean breeding value for condition has increased over time. The
      mismatch between response to selection at the levels of genotype and phenotype
      can be explained by environmental deterioration, concealing underlying evolution.
      This form of cryptic evolution may be common in natural environments.

PMID- 11452310
TI  - Cortical remodelling induced by activity of ventral tegmental dopamine neurons.
AB  - Representations of sensory stimuli in the cerebral cortex can undergo progressive
      remodelling according to the behavioural importance of the stimuli. The cortex
      receives widespread projections from dopamine neurons in the ventral tegmental
      area (VTA), which are activated by new stimuli or unpredicted rewards, and are
      believed to provide a reinforcement signal for such learning-related cortical
      reorganization. In the primary auditory cortex (AI) dopamine release has been
      observed during auditory learning that remodels the sound-frequency
      representations. Furthermore, dopamine modulates long-term potentiation, a
      putative cellular mechanism underlying plasticity. Here we show that stimulating
      the VTA together with an auditory stimulus of a particular tone increases the
      cortical area and selectivity of the neural responses to that sound stimulus in
      AI. Conversely, the AI representations of nearby sound frequencies are
      selectively decreased. Strong, sharply tuned responses to the paired tones also
      emerge in a second cortical area, whereas the same stimuli evoke only poor or non
      selective responses in this second cortical field in naive animals. In addition,
      we found that strong long-range coherence of neuronal discharge emerges between
      AI and this secondary auditory cortical area.

PMID- 11452311
TI  - The glyoxylate cycle is required for fungal virulence.
AB  - Candida albicans, a normal component of the mammalian gastrointestinal flora, is
      responsible for most fungal infections in immunosuppressed patients. Candida is
      normally phagocytosed by macrophages and neutrophils, which secrete cytokines and
      induce hyphal development in this fungus. Neutropenic patients, deficient in
      these immune cells, are particularly susceptible to systemic candidiasis. Here we
      use genome-wide expression profiles of the related yeast Saccharomyces cerevisiae
      to obtain a signature of the events that take place in the fungus on ingestion by
      a mammalian macrophage. Live S. cerevisiae cells isolated from the phagolysosome
      are induced for genes of the glyoxylate cycle, a metabolic pathway that permits
      the use of two-carbon compounds as carbon sources. In C. albicans, phagocytosis
      also upregulates the principal enzymes of the glyoxylate cycle, isocitrate lyase
      (ICL1) and malate synthase (MLS1). Candida albicans mutants lacking ICL1 are
      markedly less virulent in mice than the wild type. These findings in fungi, in
      conjunction with reports that isocitrate lyase is both upregulated and required
      for the virulence of Mycobacterium tuberculosis, demonstrate the wide-ranging
      significance of the glyoxylate cycle in microbial pathogenesis.

PMID- 11452312
TI  - Insights into Wnt binding and signalling from the structures of two Frizzled
      cysteine-rich domains.
AB  - Members of the Frizzled family of seven-pass transmembrane proteins serve as
      receptors for Wnt signalling proteins. Wnt proteins have important roles in the
      differentiation and patterning of diverse tissues during animal development, and
      inappropriate activation of Wnt signalling pathways is a key feature of many
      cancers. An extracellular cysteine-rich domain (CRD) at the amino terminus of
      Frizzled proteins binds Wnt proteins, as do homologous domains in soluble
      proteins-termed secreted Frizzled-related proteins-that function as antagonists
      of Wnt signalling. Recently, an LDL-receptor-related protein has been shown to
      function as a co-receptor for Wnt proteins and to bind to a Frizzled CRD in a Wnt
      dependent manner. To investigate the molecular nature of the Wnt signalling
      complex, we determined the crystal structures of the CRDs from mouse Frizzled 8
      and secreted Frizzled-related protein 3. Here we show a previously unknown
      protein fold, and the design and interpretation of CRD mutations that identify a
      Wnt-binding site. CRDs exhibit a conserved dimer interface that may be a feature
      of Wnt signalling. This work provides a framework for studies of homologous CRDs
      in proteins including muscle-specific kinase and Smoothened, a component of the
      Hedgehog signalling pathway.

PMID- 11452313
TI  - Mitochondrial endonuclease G is important for apoptosis in C. elegans.
AB  - Programmed cell death (apoptosis) is a tightly regulated process of cell
      disassembly in which dying cells and their nuclei shrink and fragment and the
      chromosomal DNA is degraded into internucleosomal repeats. Here we report the
      characterization of the cps-6 gene, which appears to function downstream of, or
      in parallel to, the cell-death protease CED-3 of Caenorhabditis elegans in the
      DNA degradation process during apoptosis. cps-6 encodes a homologue of human
      mitochondrial endonuclease G, and its protein product similarly localizes to
      mitochondria in C. elegans. Reduction of cps-6 activity caused by a genetic
      mutation or RNA-mediated interference (RNAi) affects normal DNA degradation, as
      revealed by increased staining in a TUNEL assay, and results in delayed
      appearance of cell corpses during development in C. elegans. This observation
      provides in vivo evidence that the DNA degradation process is important for
      proper progression of apoptosis. CPS-6 is the first mitochondrial protein
      identified to be involved in programmed cell death in C. elegans, underscoring
      the conserved and important role of mitochondria in the execution of apoptosis.

PMID- 11452314
TI  - Endonuclease G is an apoptotic DNase when released from mitochondria.
AB  - Nucleosomal fragmentation of DNA is a hallmark of apoptosis (programmed cell
      death), and results from the activation of nucleases in cells undergoing
      apoptosis. One such nuclease, DNA fragmentation factor (DFF, a caspase-activated
      deoxyribonuclease (CAD) and its inhibitor (ICAD)), is capable of inducing DNA
      fragmentation and chromatin condensation after cleavage by caspase-3 (refs
      2,3,4). However, although transgenic mice lacking DFF45 or its caspase cleavage
      site have significantly reduced DNA fragmentation, these mice still show residual
      DNA fragmentation and are phenotypically normal. Here we report the
      identification and characterization of another nuclease that is specifically
      activated by apoptotic stimuli and is able to induce nucleosomal fragmentation of
      DNA in fibroblast cells from embryonic mice lacking DFF. This nuclease is
      endonuclease G (endoG), a mitochondrion-specific nuclease that translocates to
      the nucleus during apoptosis. Once released from mitochondria, endoG cleaves
      chromatin DNA into nucleosomal fragments independently of caspases. Therefore,
      endoG represents a caspase-independent apoptotic pathway initiated from the
      mitochondria.

PMID- 11452318
TI  - Genetic relationships among serogroup B: serotype 4 Neisseria meningitidis
      strains.
AB  - We compared the results obtained by serotyping of PorB epitopes using an expanded
      panel of monoclonal antibodies (mAb) including mAb 7 and mAb 10, with results
      obtained by RFLP of rRNA genes (ribotyping). The purpose of this study was to
      assess the correlation between phenotypic- and genotypic- methods for typing N.
      meningitidis. The ribotypes obtained using ClaI or EcoRV endonucleases grouped
      the strains in seven and two different patterns, respectively. This additional
      characterization of PorB epitopes improved the correlation between these two
      methods of typing N. meningitidis.

PMID- 11452319
TI  - Clinical patterns and seasonal trends in respiratory syncytial virus
      hospitalizations in Sao Paulo, Brazil.
AB  - The respiratory viruses are recognized as the most frequent lower respiratory
      tract pathogens for infants and young children in developed countries but less is
      known for developing populations. The authors conducted a prospective study to
      evaluate the occurrence, clinical patterns, and seasonal trends of viral
      infections among hospitalized children with lower respiratory tract disease
      (Group A). The presence of respiratory viruses in children's nasopharyngeal was
      assessed at admission in a pediatric ward. Cell cultures and immunofluorescence
      assays were used for viral identification. Complementary tests included blood and
      pleural cultures conducted for bacterial investigation. Clinical data and
      radiological exams were recorded at admission and throughout the hospitalization
      period. To better evaluate the results, a non- respiratory group of patients
      (Group B) was also constituted for comparison. Starting in February 1995, during
      a period of 18 months, 414 children were included- 239 in Group A and 175 in
      Group B. In Group A, 111 children (46.4%) had 114 viruses detected while only 5
      children (2.9%) presented viruses in Group B. Respiratory Syncytial Virus was
      detected in 100 children from Group A (41.8%), Adenovirus in 11 (4.6%), Influenza
      A virus in 2 (0.8%), and Parainfluenza virus in one child (0.4%). In Group A,
      aerobic bacteria were found in 14 cases (5.8%). Respiratory Syncytial Virus was
      associated to other viruses and/or bacteria in six cases. There were two seasonal
      trends for Respiratory Syncytial Virus cases, which peaked in May and June. All
      children affected by the virus were younger than 3 years of age, mostly less than
      one year old. Episodic diffuse bronchial commitment and/or focal alveolar
      condensation were the clinical patterns more often associated to Respiratory
      Syncytial Virus cases. All children from Group A survived. In conclusion, it was
      observed that Respiratory Syncytial Virus was the most frequent pathogen found in
      hospitalized children admitted for severe respiratory diseases. Affected children
      were predominantly infants and boys presenting bronchiolitis and focal
      pneumonias. Similarly to what occurs in other subtropical regions, the virus
      outbreaks peak in the fall and their occurrence extends to the winter, which
      parallels an increase in hospital admissions due to respiratory diseases.

PMID- 11452320
TI  - Sexual transmission of hepatitis C virus.
AB  - In order to contribute to a better understanding of the forms of acquisition of
      hepatitis C virus (HCV) in Brazil, with special emphasis on sexual transmission,
      we determined the presence of HCV infection in regular partners and in non-sexual
      home communicants of blood donors seen at Fundacao Pro-Sangue Hemocentro de Sao
      Paulo from January 1992 to July 1996. Of 154 blood donors with HCV infection
      (index cases), 111 had had regular partners for at least 6 months. Sixty-eight of
      111 partners were evaluated for HCV infection. Of these, 8 (11.76%) were
      considered to have current or previous HCV infection; a history of sexually
      transmissible diseases and index cases with a positive HCV-RNA test were more
      prevalent among partners with HCV infection. Of the 68 index cases whose partners
      were studied, 56 had non-sexual home communicants. Of the total of 81 home
      communicants, 66 accepted to be evaluated for HCV infection. None of them was HCV
      positive, suggesting that the high prevalence of HCV infection among partners may
      be attributed at least partially to sexual transmission.

PMID- 11452321
TI  - Hepatitis B vaccine in infants: a randomized controlled trial comparing gluteal
      versus anterolateral thigh muscle administration.
AB  - A significantly diminished antibody response to hepatitis B vaccine has been
      demonstrated in adults when the buttock is used as the injection site. However,
      in Brazil, the buttock continues to be recommended as site of injection for
      intramuscular administration of vaccines in infants. In this age group, there are
      no controlled studies evaluating the immunogenicity of the hepatitis B vaccine
      when administered at this site. In the present study, 258 infants were randomized
      to receive the hepatitis B vaccine either in the buttock (n = 123) or in the
      anterolateral thigh muscle (n = 135). The immunization schedule consisted of
      three doses of hepatitis B vaccine (Engerix Bregister mark or target, 10 microg)
      at 2, 4 and 9 months of age. There were no significant differences in the
      proportion of seroconversion (99.3% x 99.2%), or in the geometric mean titer of
      ELISA anti-HBs (1,862.1 x 1,229.0 mIU/mL) between the two groups. This study
      demonstrates that a satisfactory serological response can be obtained when the
      hepatitis B vaccine is administered intramuscularly into the buttock.

PMID- 11452322
TI  - Microbicidal effect of medicinal plant extracts (Psidium guajava Linn. and Carica
      papaya Linn.) upon bacteria isolated from fish muscle and known to induce
      diarrhea in children.
AB  - Out of the twenty-four samples of shrimp and fish muscle used for this study,
      twelve were collected near a large marine sewer for waste disposal, 3 km off the
      coast of Fortaleza (Brazil) and used for the isolation of E. coli. Other twelve
      were collected at the Mucuripe fresh fish market (Fortaleza, Brazil) and used for
      the isolation of Staphylococcus aureus. Ethanol, water and acetone-diluted
      extracts of guava and papaya leaf sprouts were tested on the bacteria in order to
      verify their microbicidal potential. The E. coli strains used in the trials were
      rated LT positive. The papaya leaf extracts (Carica papaya Linn) showed no
      microbicidal activity while the guava sprout extracts (Psidium guajava Linn)
      displayed halos exceeding 13 mm for both species, an effect considered to be
      inhibitory by the method employed. Guava sprout extracts by 50% diluted ethanol
      most effectively inhibited E. coli (EPEC), while those in 50% acetone were less
      effective. It may be concluded that guava sprout extracts constitute a feasible
      treatment option for diarrhea caused by E. coli or by S. aureus-produced toxins,
      due to their quick curative action, easy availability in tropical countries and
      low cost to the consumer.

PMID- 11452323
TI  - Importance of hand germ contamination in health-care workers as possible carriers
      of nosocomial infections.
AB  - The importance of hands in the transmission of nosocomial infection has been
      world wide admitted. However, it is difficult to induce this behavior in health
      care workers. The aim of the present work was to point out the importance of hand
      bacteria colonization, the influence of hand washing and of patient physical
      examination. One hundred health-care workers were randomly divided in two groups:
      Group A without hand washing previous to patient physical examination or handling
      (PPE); group B with hand washing previous to PPE. Direct fingerprint samples in
      Columbia agar before and after PPE were obtained. The colonies were counted and
      identified by conventional techniques, and antibiograms according to NCCLS were
      performed. Before PPE group A participants showed a high number of bacteria
      regarding group B participants (73.9 Vs 20.7; p < 0.001); 44 out of 50
      participants were carriers of potentially pathogen bacteria. No group B
      participants were carriers of potential pathogen bacteria before PPE. The latter
      group showed an increase in number of bacteria after PPE (20.7 CFU (before) Vs
      115.9 CFU (after); p < 0.001). Sixteen group B participants were contaminated
      after PPE with potential pathogens such as S. aureus (50% of them methicillin
      resistant); Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis,
      half of them multiresistant. We can conclude on the importance of these results
      to implement educational programs and to provide the health-care workers with the
      proper commodities to fulfill this practice.

PMID- 11452324
TI  - Evaluation of anti-Schistosoma mansoni IgG antibodies in patients with chronic
      schistosomiasis mansoni before and after specific treatment.
AB  - The circumoval precipitin test (COPT), enzyme-linked immunosorbent assay (ELISA)
      and the immunoblotting anti-adult worm antigen (AWA) and soluble egg antigen
      (SEA) tests were applied to 17 chronically schistosome-infected patients for the
      detection of anti-Schistosoma mansoni antibodies before and on four occasions
      after oxamniquine administration over a period of six months. Compared to a
      control group, schistosomiasis patients showed high levels of IgG antibodies in
      AWA and SEA-ELISA. A decrease in IgG levels was observed six months after
      treatment, although negative reactions were not obtained. Significant decreases
      in IgG1, IgG3 and, mainly, IgG4, but not anti-SEA IgG2 levels were observed six
      months after treatment, again without negativity. Analysis of anti-AWA IgG
      antibodies by immunoblotting before treatment showed a 31 kDa strand in 14
      patients (82%) which disappeared in three cases up to six months after treatment;
      furthermore, anti-SEA IgG antibodies showed the same band in nine patients (53%)
      before treatment, which disappeared in only four cases up to six months after
      treatment.

PMID- 11452325
TI  - Pasteurization of human milk to prevent transmission of Chagas disease.
AB  - Although admittedly transmission of Trypanosoma cruzi infection through
      breastfeeding is a rare event, it involves serious risks. To test the
      effectiveness of pasteurization in preventing this mode of infection, three sets
      of samples of human milk were tested: a - contaminated with T. cruzi and
      pasteurized; b - contaminated with T. cruzi and non-pasteurized; c - non
      contaminated and pasteurized. Samples from all sets were orally and
      intraperitoneally administered to 90 BALB/c mice. The animals inoculated with
      contaminated, non-pasteurized samples, got the infection. Controls and the
      animals inoculated with contaminated and pasteurized milk were not infected. The
      hypothesis was accepted that pasteurization inactivates T. cruzi trypomastigotes.

PMID- 11452326
TI  - Phialemonium curvatum infection after bone marrow transplantation.
AB  - We report a case of cutaneous infection caused by Phialemonium curvatum GAMS et
      COOKE, 1983, after bone marrow transplantation. The genus Phialemonium was
      created by GAMS & MCGINNIS in 1983 including three new species: Ph. obovatum, Ph.
      curvatum and Ph. dimorphosporum, and represents an intermediate genus between
      Acremonium and Phialophora. Nowadays, the genus Phialemonium is considered to be
      a pheoid fungus which may cause the eventual lesions observed in pheo- and
      hyalohyphomycosis. Species of this genus have been described as opportunistic
      agents in humans and animals, mainly as a result of immunosuppression. In the
      present case, the patient had multiple myeloma and received an allogenic bone
      marrow transplant from his HLA-compatible brother. Two months after
      transplantation, he developed purplish and painful nodular lesions on the right
      ankle. Some of these lesions drained spontaneously and apparently hyaline
      mycelial filaments were observed, whose culture was initially identified as
      Acremonium sp. Subsequent studies showed that the fungus was Phialemonium
      curvatum. The infection was treated with amphotericin B, followed by
      ketoconazole. The patient was submitted to surgical debridement followed by two
      skin grafts to repair the bloody area. The duration of the treatment was 4 months
      and secondary prophylaxis with ketoconazole alone was maintained for one
      additional month. No recurrence was observed after discontinuation of treatment.
      The authors comment on the pathogenicity of the genus Phialemonium.

PMID- 11452327
TI  - Papular-purpuric "gloves and socks" syndrome due to parvovirus B19: report of a
      case with unusual features.
AB  - We present a case of papular-purpuric "gloves and socks" syndrome (PPGSS) in an
      adult male with acute parvovirus B19 infection. The patient displayed the
      classical features of fever, oral lesions, and purpura on hands and feet, but the
      purpuric lesions on the feet evolved to superficial skin necrosis, a feature not
      previously described in this syndrome. We believe this is the first reported case
      of PPGSS occurring in Brazil.

PMID- 11452328
TI  - Seabather's eruption: report of five cases in southeast region of Brazil.
AB  - The authors report five cases of seabather's eruption, a typical dermatitis
      associated predominantly to the jellyfish Linuche unguiculata (Cnidaria), that
      causes erythematous and pruriginous papules on areas of the skin of bathers
      covered by swimsuits. The rash is characteristic and the eruption is commom in
      the Caribbean, Florida, Mexico and Gulf States of USA. The cases are the first
      reported in Brazil and larvae of the jellyfish are present in the waters where
      the accidents happened.

PMID- 11452329
TI  - Etiological treatment of chronic Chagas disease.

PMID- 11452331
TI  - Will antiarrhythmic drug therapy guided by electrophysiology study survive in the
      new millennium?

PMID- 11452332
TI  - Arterial elastance and wave reflection augmentation of systolic blood pressure:
      deleterious effects and implications for therapy.
AB  - Systolic and pulse blood pressures are stronger predictors of stroke, coronary
      heart disease, myocardial infarction, heart failure, end-stage renal disease, and
      cardiovascular mortality than diastolic pressure. Furthermore, diastolic pressure
      is inversely related to coronary heart disease and cardiovascular mortality.
      Increased elastance (or stiffness, inverse of compliance) of the central elastic
      arteries is the primary cause of increased systolic and pulse pressure with
      advancing age and in patients with cardiovascular disease, including
      hypertension, and is due to degeneration and hyperplasia of the arterial wall;
      diastolic pressure decreases as arterial elastance increases. As elastance
      increases, transmission velocity of both forward and backward (or reflected)
      traveling waves increases, which causes the reflected wave to arrive earlier in
      the central aorta and augments pressure in late systole. These changes in
      arterial wall properties cause an increase in left ventricular afterload and
      myocardial oxygen consumption and a decrease in myocardial perfusion pressure,
      which may induce an imbalance in the supply-demand ratio, especially in
      hypertrophied hearts with coronary artery disease. Also, an increase in systolic
      pressure increases arterial wall circumferential stress, which promotes fatigue
      and development of atherosclerosis. Vasodilator drugs have little direct active
      effect on large elastic arteries but can markedly reduce wave reflection
      amplitude and augmentation index by decreasing elastance of the muscular arteries
      and reducing pulse wave velocity of the reflected wave from the periphery to the
      heart. This decrease in intensity (or amplitude) and increase in travel time (or
      delay) of the reflected wave causes a generalized decrease in systolic pressure
      and arterial wall stress and an increase in ascending aortic flow during the
      deceleration phase. The decrease in systolic pressure brought about by this
      mechanism is grossly underestimated when systolic pressure is measured in the
      brachial artery.

PMID- 11452333
TI  - Exercise tolerance and quality of life in elderly patients with chronic atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common arrhythmia affecting the
      elderly. Although the risk of cardioembolic stroke is well defined, the effects
      of chronic atrial fibrillation on exercise tolerance and quality of life have
      been less well quantified. METHODS: We compared a group of 52 elderly patients
      with chronic atrial fibrillation to a group of 48 control patients in sinus
      rhythm. Each patient underwent an interview that incorporated the Short Form-36
      Health Survey (SF-36) to quantify individual perceptions on quality of life. In
      addition each person underwent physiologic testing that included a Modified Bruce
      Protocol exercise tolerance test, 24-hour ambulatory monitor test, and an
      echocardiogram. RESULTS: Both groups were elderly, 77 vs 76 years of age
      (P=0.35). The two groups had similar ejection fractions, 55.4% vs 58.4% (P=0.10).
      The atrial fibrillation patients demonstrated a higher level of comorbidity based
      on the Charlson Comorbidity Index, 2.46 vs 1.57 (P=0.03). On formal exercise
      testing there was no statistical difference in exercise duration between the two
      groups 9.0 vs 10.1 minutes (P=0.24). Similarly the Physical Summary Score (PCS)
      and the Mental Summary Score (MCS) of the SF-36 quality of life survey did not
      demonstrate a statistical difference between the two groups. PCS: 43.0 vs 45.9
      (P=0.24); MCS: 52.5 vs 55.7 (P=0.07). CONCLUSIONS: Despite a higher level of
      comorbidity, elderly, ambulatory patients with chronic atrial fibrillation
      demonstrate similar exercise tolerance and report similar quality of life to a
      group of age-matched control patients in sinus rhythm. There is a cohort of
      patients in chronic atrial fibrillation in whom a strategy of rate control and
      anticoagulation may be appropriate.

PMID- 11452334
TI  - Fenoldopam infusion associated with preserving renal function after aortic cross
      clamping for aneurysm repair.
AB  - BACKGROUND: Cross-clamping of the descending aorta during operative repairs
      causes sudden, significant reductions in renal function that may persist well
      beyond arterial clamp release. Commonly used agents, such as dopamine and
      mannitol, have not consistently affected renal outcome in these high-risk
      patients. Fenoldopam mesylate is a novel, highly selective dopamine type-1
      agonist that preferentially dilates the renal and splanchnic vasculature, but has
      not been investigated in patients undergoing prolonged aortic clamping for whom
      adverse renal outcomes should be more likely. METHODS AND RESULTS: Twenty-two
      adult patients without significant pre-existing renal dysfunction and presenting
      for elective repairs of abdominal aortic aneurysms were studied. Fenoldopain
      mesylate was infused after obtaining baseline values ranging from 0.1 to 1.0
      microg/kg/min for the first 24 hours postoperatively to maintain mean arterial
      pressure +/-25% baseline. Serial renal function indices, including creatinine
      clearance and electrolyte fractional excretions, were measured at baseline, at
      aortic clamping and unclamping, and post-clamp release, and were estimated
      through hospital discharge. Creatinine clearance fell during abdominal
      exploration and clamping, reaching a nadir with clamp removal. Partial recovery
      occurred by 2 hours after clamp removal, and returned to baseline values by
      postoperative day 1 and thereafter. Fractional excretions rose rapidly throughout
      the operative phase. Total fenoldopam dose was directly related to the baseline
      creatinine clearance; after clamp removal, creatinine clearance was directly
      related to the mean arterial pressure at the lowest dose of fenoldopam, and
      inversely related to the mean arterial pressure at clamp release. CONCLUSIONS: In
      elderly patients with severe vascular disease undergoing aneurysmal repairs, the
      use of a fenoldopam infusion in this open-label, uncontrolled trial was
      associated with a relatively rapid return of renal function to baseline values,
      despite profound decreases during aortic cross-clamping. Further studies will be
      necessary to investigate how fenoldopam infusions compare with traditional
      therapies.

PMID- 11452335
TI  - The effect of agmatine administration on ischemic-reperfused isolated rat heart.
AB  - BACKGROUND: The natural polyamine Agmatine (Ag) plays a significant role in
      protection of nerve cell ischemic injury. A previous report indicated that Ag
      given intraperitoneally to rats enhanced the recovery of the heart from ischemic
      injury. Based on this initial observation, a larger investigation was undertaken
      to explore a dose-response effect and possible mechanisms underlying the
      protective effects. METHODS: Using the modified Langendorff model, 36 isolated
      hearts were divided into five groups: group 1, hearts receiving 100 microM/L Ag
      pre-ischemia (n=7); group 2, hearts receiving 100 microM/L Ag pre- and post
      ischemia, (n=7); group 3, hearts receiving 250 microM/L Ag pre-ischemia (n=7);
      group 4, hearts receiving 250 microM/L Ag pre- and postischemia (n=7); and group
      5, hearts receiving Krebs-Hensleit solution served as control (n=8). The study
      design included 20 minutes of perfusion, 30 minutes of global ischemia, and 30
      minutes of reperfusion. RESULTS: After ischemia, group 2 developed higher left
      ventricular pressure P(max) (P<0.01), improved first-derivative of the rise
      (dP/dt max; P<0.02), and fall (dP/dt min; P<0.04) in left ventricular pressure,
      and the area calculated under the left-ventricle developed pressure curve
      (pressure-time integral; P<0.015), but coronary flow was not significantly
      increased (P=0.06) compared to the control group. Group 1 had improved diastolic
      recovery: dP/dt min (P<0.05) and coronary flow (P<0.03), compared with the
      control group. Group 3 had improved P(max) (P<0.01), dP/dt min (P<0.01), and
      coronary flow (P<0.02); group 4 had no improvement in all hemodynamic parameters.
      CONCLUSION: Low doses of Ag given pre- and post-ischemia, and high doses given
      only pre-ischemia have favorable, protective effects on the hemodynamic recovery
      of isolated rat heart undergoing global ischemia and reperfusion.

PMID- 11452336
TI  - Elevated baseline triglyceride levels modulate effects of HMGCoA reductase
      inhibitors on plasma lipoproteins.
AB  - BACKGROUND: The response in levels of very-low-density (VLDL) and low-density
      (LDL) lipoproteins varies substantially among hyperlipidemic patients during
      treatment with HMGCoA reductase inhibitors. Apolipoprotein E genotype and gender
      are known to contribute to the regulation of steady state levels of plasma
      lipoproteins. This study explores the effect of these and other potential
      determinants of the response of VLDL and LDL to treatment with reductase
      inhibitors. METHODS: Using mixed linear statistical models, the response of
      lipoprotein lipid values was studied in 142 hyperlipidemic individuals who were
      treated with reductase inhibitors. Patients received one or more of the following
      drugs individually for a total of 623 treatment observations: lovastatin,
      pravastatin, simvastatin, or atorvastatin. For evaluation of the effects of
      treatment in the aggregate, actual doses were expressed as equivalent doses of
      atorvastatin, using factors based on random assignment comparisons in 16 reported
      studies. The analysis factors considered were apolipoprotein E genotype, baseline
      average triglycerides >170 mg/dL (vs less), and gender. RESULTS: Presence of an
      apo epsilon4 allele was associated with a trend toward greater reduction of
      triglyceride levels and a diminished ability of the reductase inhibitors to
      reduce LDL cholesterol levels. Gender had only minimal effect on the response of
      either LDL cholesterol or triglycerides. However, the effect of elevated baseline
      triglycerides on the response of both triglycerides and LDL cholesterol was
      striking and was exerted in opposite directions. The triglyceride-lowering effect
      of reductase inhibitors was greater in patients with initial triglyceride levels
      above 170 mg/dL (P=0.0001). The effect was even greater in patients with initial
      triglyceride levels over 250 mg/dL (P=0.015). Conversely, for LDL cholesterol
      levels, elevated baseline triglycerides were associated with a significantly
      decreased response to the drugs (P=0.0015). CONCLUSIONS: These findings indicate
      that baseline triglyceride levels are an important predictor of response of
      plasma lipoproteins to HMGCoA reductase inhibitors, perhaps reflecting
      fundamental differences in mechanism underlying the hyperlipidemic phenotype.

PMID- 11452337
TI  - Low-dose ACE with alpha- or beta-adrenergic receptor inhibitors have beneficial
      SHR cardiovascular effects.
AB  - BACKGROUND: There are no data regarding the prolonged effect of alpha-1
      adrenergic receptor antagonists on ventricular collagen content and coronary
      hemodynamics in spontaneously hypertensive rats (SHR). This study, therefore, was
      designed to determine the effects of chronic treatment with the alpha-1
      adrenergic receptor inhibitor doxazosin on SHR systemic and regional (especially
      coronary) hemodynamics, cardiovascular mass, and ventricular collagen. The
      effects of the combination of doxazosin with low-dose angiotensin-converting
      enzyme inhibitor were studied versus the alpha-1 antagonist alone. These effects
      were compared with those of a beta-1 adrenergic receptor inhibitor. METHODS AND
      RESULTS: Systemic and regional hemodynamics (radionuclide-labeled microspheres),
      left and right ventricular weight, hydroxyproline concentration, and aortic
      weight were measured at age 35 weeks. Doxazosin reduced arterial pressure and
      total peripheral resistance without changing left ventricular mass and collagen
      content, whereas monotherapies with the beta-1 antagonist metoprolol or a
      subdepressor dose of the ACE inhibitor enalapril were effective in reducing left
      ventricular mass and hydroxyproline without altering pressure. Doxazosin combined
      with the same low-dose ACE inhibitor reduced left ventricular mass and
      hydroxyproline without potentiating the hypotensive effect of doxazosin. By
      contrast, the combination of beta-1 antagonist with the low-dose ACE inhibitor
      reduced pressure, unlike either agent alone. Aortic weight index was
      significantly reduced only by doxazosin whether when used alone or with the ACE
      inhibitor. Low-dose ACE inhibitor with doxazosin or the beta-1 receptor
      antagonist as well as doxazosin alone decreased renal vascular resistance.
      CONCLUSION: These data show that the low subdepressor dose ACE inhibitor with an
      alpha- or beta-adrenergic receptor antagonist provides beneficial cardiovascular
      effects in SHR.

PMID- 11452339
TI  - Mechanisms of action of antiarrhythmic drugs relative to the origin and
      perpetuation of cardiac arrhythmias.

PMID- 11452340
TI  - Assessment of the pro-arrhythmic potential of anti-arrhythmic drugs: an
      experimental approach.

PMID- 11452341
TI  - Clinical trials of antiarrhythmic drugs in postmyocardial infarction and
      congestive heart failure patients.

PMID- 11452342
TI  - Prospective controlled study of carotid endarterectomy with hemashield patch: is
      it thrombogenic?
AB  - The use of patch angioplasty after carotid endarterectomy (CEA) has been shown to
      have superior results to CEA with primary closure. Polytetrafluoroethylene (PTFE)
      patches have been shown to have comparable results to autogenous vein patching;
      however, PTFE has the disadvantage of prolonged hemostasis time. Therefore, many
      surgeons are using collagen-impregnated Dacron patches (Hemashield[HP]). We
      believe this is the first prospective controlled study of the use of HP in
      carotid endarterectomy. This study included 144 consecutive patients who had 151
      CEAs with HP. Postoperative duplex ultrasounds were done at 1 month and every 6
      months thereafter. The mean follow-up was 12 months (range: 1-30 months).
      Indications for CEA included symptomatic (64%) and asymptomatic (36%) stenoses.
      The overall incidence of ipsilateral stroke was 5% (4% perioperative), with a
      combined TIA and stroke rate of 12%. Incidence of > or =50% recurrent stenosis
      was 21% (7% symptomatic TIA/stroke) and > or =80% recurrent stenosis was 9%.
      Kaplan-Meier analysis showed that at 1 year and 2.5 years freedom from > or =50%
      recurrent stenosis was 78% and 57%, respectively, freedom from > or =80%
      recurrent stenosis was 92% and 77%, respectively, and a stroke-free survival rate
      of 94% and 72%, respectively. Women had a 22% and men a 14% recurrent stenosis
      rate (p=0.04). There was no correlation between other specific risk factors and
      recurrent stenosis except for hypertension (33% vs 12%, p=0.003). The authors
      concluded that CEA with HP had a higher incidence of recurrent stenosis (21%),
      and a higher perioperative stroke rate (4%) after a mean follow-up of 12 months
      than previously reported using PTFE or saphenous vein patching (2% and 9%
      recurrent stenosis rates, respectively, and 1% and 0% perioperative stroke rates,
      respectively after a mean follow-up of 30 months). This raises the question as to
      whether this patch is thrombogenic in this location. Therefore, a randomized
      controlled trial comparing this patch with other patches (PTFE or vein) is
      warranted.

PMID- 11452343
TI  - A new minimally invasive method of aortofemoral revascularization.
AB  - In recent years, minimal invasive surgical applications have been used in every
      field of surgery and became a routine application for some kinds of operations.
      Mini-laparotomy has been limited to abdominal incisions between 3 and 10 cm long.
      Four aortobifemoral and one aortofemoral bypass cases that were performed with
      mini-laparotomy incision between January 1997 and February 1998 are presented. In
      all cases, revascularization of lower extremities was performed successfully
      without enlarging the incision. The average operation time was shorter and the
      number of transfused blood units was significantly lower in that group when
      compared to the conventional laparotomy group of 12 cases. In all cases, bowel
      sounds appeared in 2 to 8 hours and at the end of 24 hours, oral nutrition was
      started. The mean discharge time from the hospital was 4.7 days. With the
      advantages of less operation time, optimal aortic exposure, ability in safe cross
      clamping, less postoperative pain, less scar tissue occurrence, early resumption
      of intestinal functions, early mobilization and shorter hospitalization time, the
      mini-laparotomy technique is a safe reliable method for use in aortobifemoral
      bypass operations.

PMID- 11452344
TI  - Atraumatic acute upper limb ischemia: a series of 64 patients in a Middle East
      tertiary vascular center and literature review.
AB  - This paper documents the various causes of upper limb ischemia in a series of 64
      Egyptian patients presenting to a tertiary referral center over a 4-year period
      and offers a diagnostic dissertation and review of the pertinent literature.
      Atraumatic upper limb ischemia is an uncommon entity. It has a broad etiology
      with diverse management pathways. Nineteen patients presented with severe and
      immediate limb-threatening ischemia. These patients underwent immediate surgical
      exploration: an embolus was diagnosed in 15 and thrombosis in 4. Twenty-eight
      patients presented with ischemia of lesser severity, allowing preoperative
      angiography. Of these 28 patients, 6 had an embolus, 14 had thrombosis, 4 had
      thoracic outlet syndrome, the remainder had miscellaneous causes. Fifteen
      patients had upper limb ischemia secondary to arteritis, and 2 patients with
      dissection of the ascending thoracic aorta presented with upper limb ischemia.
      Forty-seven patients underwent a surgical procedure, with a morbidity rate of 21%
      and mortality rate of 19%. Patients presenting with upper limb ischemia tend to
      have significant co-existing disease. Management of upper limb ischemia requires
      preoperative and/or peroperative angiography with careful application of vascular
      surgical expertise.

PMID- 11452345
TI  - Arterial access site closure with a novel sealing device: Duett.
AB  - Management of arterial access sites following percutaneous endovascular
      procedures is associated with patient discomfort and local complications. A new
      vascular sealing device, comprised of a balloon delivery catheter and a flowable
      procoagulant consisting of thrombin and collagen, was tested. Immediately
      following catheterization 200 patients (age, 66.1 +/- 11.2 years) were treated
      with the sealing device (Duett). Of these 200 patients, 132 underwent diagnostic
      catheterization, 67 underwent percutaneous transluminal coronary angioplasty, and
      one underwent percutaneous transluminal angioplasty. The sheath sizes included 2
      5 Fr, 166-6 Fr, 25-7 Fr and 7-8 Fr. All patients undergoing diagnostic procedures
      received at least 5,000 U of intravenous heparin during the procedure. The Duett
      was used successfully in 198/200 (99%) patients immediately following completion
      of the endovascular procedure. In two patients a device malfunction resulted in
      uncomplicated crossover to manual compression. The time to hemostasis ranged from
      3 to 5 minutes. All patients were walking 2 to 5 hours following the procedure
      unless a complication had occurred. No patient experienced leg ischemia, required
      surgical repair of the arterial access site, or had an infection at the site. In
      three patients (1.5%), a pseudoaneurysm occurred and was successfully treated
      with ultrasound-guided compression and three patients received a blood
      transfusion. No late complications were observed following hospital discharge.
      This novel vascular sealing device successfully achieves rapid hemostasis and
      allows early ambulation following percutaneous endovascular procedures with a low
      incidence of complications.

PMID- 11452346
TI  - Changing patterns of access site complications with the use of percutaneous
      closure devices.
AB  - The authors report their experience with 15 cases of groin complications
      associated with the use of percutaneous closure devices following femoral
      arterial catheterization over a 2-year period. The complication rate was 1.7% for
      catheterizations in which a closure device was used. The 15 cases included 7
      uncomplicated pseudoaneurysms (PSA), 3 infected pseudoaneurysms, 4 nonarterial
      groin infections (infected hematomas and/or abscesses), and 1 case of femoral
      artery occlusion. These complications presented at an average of 5 +/- 4 days
      postcatheterization. One patient with an infected PSA required a below-the-knee
      amputation. During the same time interval, there were no infectious complications
      in patients not receiving closure devices. We conclude that groin complications
      associated with such devices tend to present late and include a higher percentage
      of infections as opposed to complications occurring in patients not receiving
      closure devices. An aggressive surgical approach to these problems appears
      warranted.

PMID- 11452347
TI  - Aortocava fistula: experience with five patients.
AB  - Combined injuries of the aorta and inferior vena cava are rare. Mortality is over
      70%, primarily from exsanguinating hemorrhage. Post-traumatic aortocava fistula
      can develop in survivors, who present in the postoperative period with
      manifestations of high output heart failure. This is a retrospective review of
      five male patients, age from 9 to 39 years, with aortocava fistulas that were
      referred with congestive heart failure, 2 days to 6 months after abdominal
      penetrating injuries. They had undergone surgery at another hospital and several
      organ injuries were treated. Retroperitoneal hematomas were not seen or were seen
      and left undisturbed. Four patients received a gunshot injury, had the fistula at
      the infrarenal level, and survived surgical repair. In one of the survivors, a
      left popliteal artery bullet embolism also occurred and was treated. Another
      patient sustained a thoracoabdominal stab injury and an aortocava fistula
      developed at the suprarenal level; he was in severe congestive heart failure and
      died during surgery. There are very few reports on this sequelae of vascular
      injuries at the abdominal level. Patients with aortic and cava injuries have a
      high mortality rate and arteriovenous fistula may develop with communicating
      pseudoaneurysms. If high output heart failure develops in a patient with a
      history of abdominal penetrating injury, an arteriovenous fistula must be
      suspected and arteriography will disclose the location of the fistula. Surgical
      treatment is necessary to prevent further heart damage. In the future
      endovascular procedures may have a role in the management of these difficult
      conditions.

PMID- 11452348
TI  - Vascular surgeon Edwin J. Wylie, MD (1918-1982), pioneer and visionary.

PMID- 11452349
TI  - Bilateral spontaneous dissection of the internal carotid arteries--a case report.
AB  - A 41-year-old African American man presented with an acute stroke secondary to
      bilateral spontaneous internal carotid artery dissections following exercise.
      Spontaneous bilateral carotid artery dissection is an unusual and uncommon
      occurrence that can be successfully diagnosed by color-flow duplex
      ultrasonography and magnetic resonance imaging/magnetic resonance angiography
      (MRI/MRA) imaging. A review of the literature and the authors' experience
      supports initial medical management of these patients. Surgery should be
      considered for those patients who exhibit progressive neurologic symptoms during
      medical management or when significant carotid artery complications, aneurysms,
      or flow-limiting stenoses persist.

PMID- 11452350
TI  - Bilateral extracranial aneurysm of the internal carotid artery--a case report.
AB  - The authors report a case study of a 78-year-old man with a bilateral
      extracranial atherosclerotic aneurysm of the internal carotid artery. The patient
      was treated surgically with resection of the aneurysm and restoration of the flow
      with a polytetrafluoroethylene (PTFE) graft. The postoperative period was
      uneventful. Histologic tests demonstrated almost complete destruction of the
      elastin fibers. The potential hazards of an aneurysm of the internal carotid
      artery indicate that surgical treatment is warranted.

PMID- 11452351
TI  - Thoracoabdominal aortic aneurysms repair under abdominal cavity cooling with
      visceral shunting technique--a case report.
AB  - Mild hypothermia induced by abdominal cavity cooling together with a selective
      visceral shunting technique can be a useful adjunct for thoracoabdominal aortic
      aneurysm repair. The authors adopted this combined technique for repair of
      selected Crawford type III and type IV aneurysms to reduce visceral ischemic
      damage and minimize the incidence of postoperative complications.

PMID- 11452352
TI  - Common iliac artery pseudoaneurysm following inguinal hernia repair--a case
      report and literature review.
AB  - The authors report a patient presented with a ruptured infected iliac artery
      pseudoaneurysm 2 weeks after ipsilateral inguinal hernia repair. Pseudoaneurysms
      that occur because of infection develop rapidly and mandate ligation of the
      affected artery and extraanatomic bypass. Noninfected pseudoaneurysms are usually
      discovered incidentally and may be managed with either endovascular or standard
      surgical techniques. A percutaneously placed aortic occlusion balloon may prevent
      exsanguination, when used as an adjunct to surgical repair in cases of ruptured
      pseudoaneurysm.

PMID- 11452353
TI  - Buerger's disease affecting mesenteric arteries: a rare cause of intestinal
      ischemia--a case report.
AB  - Buerger's disease is a recurrent, inflammatory, segmental, vasoocclusive disease.
      Typically, the disease affects middle-aged male smokers and involves arteries and
      veins of extremities. Buerger's disease involving visceral vessels is rare. The
      authors report on a 51-year-old man with peripheral arterial disease and
      recurrent intestinal ischemia secondary to Buerger's disease. Clinical and
      histopathologic features of this case illustrate the life-threatening nature of
      visceral involvement in Buerger's disease.

PMID- 11452354
TI  - Aortic nonanastomotic pseudoaneurysm eroding lumbar vertebra--a case report.
AB  - Nonanastomotic pseudoaneurysms are uncommon complications of prosthetic grafts,
      which are mostly associated with axillofemoral grafts. The case presented
      describes a pseudoaneurysm secondary to a previously placed end-to-side
      aortobifemoral bypass. Back pain developed 3 years after the original bypass and
      was not relieved with narcotics and muscle relaxants. The patient also complained
      of a 20-pound weight loss, night sweats, and frequent emesis. Approximately 1
      year after the onset of back pain, left leg claudication developed. He eventually
      underwent magnetic resonance imaging of the lumbosacral spine, which depicted a
      tumorlike mass eroding the vertebral bodies of L2 and L3. Full oncologic workup
      was pursued preoperatively. The patient also underwent aortography, computed
      tomography of the abdomen and pelvis, and an inferior venacavogram to elucidate
      the relationships between the mass and the major vascular structures. On
      exploration, no malignancy was present. A hole in the native aorta approximately
      2 cm above the level of the end-to-side aortic anastomosis was discovered. This
      was contiguous with the vertebral bodies and the left psoas muscle. The
      pseudoaneurysm was repaired by conversion of the proximal anastomosis to an end
      to-end aorto right iliac and left femoral bypass. All of the preoperative
      symptoms resolved after repair of the pseudoaneurysm. Chronic aortic rupture or
      pseudoaneurysms are difficult to diagnose due to the unusual clinical
      presentations. Despite complete radiologic evaluation, preoperative diagnosis may
      be difficult or impossible without a high degree of suspicion. Surgical repair
      will depend on the cause of the pseudoaneurysm--all but infected aneurysms may be
      repaired in line by creating a proximal anastomosis above the level of the
      pseudoaneurysm. Atypical back pain in patients with previous aortic
      reconstructions should alert the clinician to the possibility of vascular
      involvement. Patients with aortic pseudoaneurysms should undergo prompt repair to
      avert the potential risk for rupture when the surrounding structures are no
      longer able to contain the pulsatile flow.

PMID- 11452355
TI  - Deposition of fine and coarse aerosols in a rat nasal mold.
AB  - The objective of this study was to investigate the deposition characteristics of
      large, inhalable particles in rat nasal passages by determining the deposition
      efficiencies of these particles in a nasal mold of an F344 rat for steady-state
      and pulsating flow conditions. Particles with geometric diameters ranging from
      0.5 to 4 microm and flow rates ranging from 100 to 900 ml/min were employed for
      simulated inspiratory and expiratory flow situations. The optically clear acrylic
      mold was fabricated from a life-size metal cast that comprised the nares, nasal
      cavity, pharynx, and larynx. Deposition efficiencies were calculated for each
      flow situation and plotted as functions of particle inertia. Inspiratory and
      expiratory deposition efficiencies were similar for a given flow condition.
      Deposition efficiencies for the cases of pulsating flows were markedly higher
      than those of steady flows. The results for pulsating flows indicated higher
      deposition efficiencies than were found in previous studies performed with live
      rats. These differences may be due to uncertainties in particle inhalability,
      clearance, and flow rate in the previous studies, as well as differences between
      the nasal geometries of live rats and the geometry of the nasal mold made from a
      postmortem cast. The results suggest that the pulsating nature of breathing is an
      important consideration when determining the deposition of fine and coarse
      particles.

PMID- 11452356
TI  - Comparison of gene expression of cytokines mRNA in lungs of rats induced by
      intratracheal instillation and inhalation of mineral fibers.
AB  - To investigate whether the results of intratracheal instillation studies on
      mineral fibers reflect the findings obtained by long-term inhalation data on
      mineral fibers, we have examined gene expression of cytokines and pathological
      features in lungs induced by intratracheal instillation and inhalation of mineral
      fibers. Male Wistar rats were given a single intratracheal instillation of 2 mg
      alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (PT1),
      and were sacrificed 4 wk after the fiber instillation. Long-term inhalation
      studies were also performed. In these, animals were exposed to fiber aerosol of
      RF1 or PT1 for 5 days/wk for 1 yr, and sacrificed after 1 yr of inhalation.
      Expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
      transforming growth factor-beta1 (TGF-beta1) from lungs was observed by reverse
      transcription polymerase chain reaction (RT-PCR). The expression of TNF-alpha, IL
      6, and TGF-beta1 mRNA in PT1-exposed lung was significantly higher than for those
      exposed to RF1 in both intratracheal instillation and inhalation studies.
      Pathological findings revealed that mild pulmonary fibrosis was seen in the lungs
      after intratracheal instillation and inhalation of PT1 but not RF1. Similarities
      were observed not only in gene expression of cytokines but in pathological
      features between both studies. These data suggested that the results of
      intratracheal instillation reflect the findings obtained from long-term
      inhalation data.

PMID- 11452357
TI  - Chronic inhalation studies of two types of stone wool fibers in rats.
AB  - A summary is given of the pathology results after long-term inhalation in rats of
      insulation wool representing the new biosoluble types. The pathology results are
      compared with previously conducted long-term inhalation study with MMVF21
      (traditional stone wool). The biosoluble fiber MMVF34/HT (HT) is characterized by
      a relatively high content of aluminum and a relatively low content of silica
      compared to the older MMVF21. HT has a high in vitro dissolution rate at pH 4.5,
      and a relatively low dissolution rate at pH 7.5. Male Fischer 344 rats were
      exposed at one exposure level of 30 mg/m(3) by nose-only inhalation of a well
      characterized fiber test atmosphere. The fibers had been size selected to be
      largely rat respirable. The negative control group was exposed to filtered air.
      The exposure duration was 6 h/day, 5 days/wk for 104 wk, with a subsequent
      nonexposure period lasting until approximately 20% survival in the air control
      group. Interim sacrifices were performed at wk 13, 26, 52, 78, and 104 to monitor
      the progression of pulmonary change and fiber numbers. Effectively the main
      protocol for the previously conducted chronic study with MMVF21 was the same,
      except that there were three concentration levels (3, 16, and 30 mg/m(3)). In
      addition to the endpoints measured in the previous study, slides from both
      studies were evaluated for collagen deposition using a quantitative morphometric
      method. The results of the comparative study clearly showed a marked difference
      in the pulmonary pathogenicity of the MMVF21 and HT in terms of their fibrogenic
      potential. MMVF21 caused pulmonary fibrosis, but the HT fiber did not. The
      incidence of tumors for both the HT and the MMVF21 fiber was comparable to the
      control groups.

PMID- 11452358
TI  - Bioaccumulation and locomotor effect of manganese dust in rats.
AB  - The primary goal of this study is to determine the effects of Mn exposure via
      inhalation. The bioaccumulation of Mn in different organs and tissues, the
      alteration of biochemical parameters, and the locomotor activity were assessed. A
      group of 26 male Sprague-Dawley rats (E) were exposed to 3750 microg/m(3) of Mn
      dust for 6 h/day, 5 days/wk for 13 consecutive weeks and compared to a control
      group of 12 rats (C) exposed to 4 microg/m(3). After exposure, neurological
      evaluation was carried out for 36 h (a night-day-night cycle) using a
      computerized autotrack system. Rats were then sacrificed by exsanguination, and
      Mn content in organs and tissues was determined by neutron activation analysis.
      Mn concentrations in lung, putamen, and cerebellum were significantly higher in E
      than in C (0.30 vs. 0.17, 0.89 vs. 0.44, 0.63 vs. 0.48 ppm; p <.01), as well as
      in the kidney, frontal cortex, and globus pallidus (1.15 vs. 0.96, 0.84 vs. 0.47,
      1.28 vs. 0.55 ppm; p <.05). Potassium concentration was significantly lower in E
      than in C (5.11 vs. 5.79 mmol/L; p <.05), as was alkaline phosphatase (106.9 vs.
      129.6 U/L; p <.01). Locomotor activity indicated higher distance covered in the
      first 12-h period for E (45 383 vs. 36 098 cm; p <.05) and lower resting time in
      the last 12-h period for E (36 326 vs. 37 393 s; p <.05). This study is the first
      of several ongoing studies in our laboratory that address health concerns
      associated with inhalation exposure to different Mn species and to different
      levels of exposure.

PMID- 11452359
TI  - Two genes that map to the STSL locus cause sitosterolemia: genomic structure and
      spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and
      ABCG8, respectively.
AB  - Sitosterolemia is a rare autosomal recessive disorder characterized by (a)
      intestinal hyperabsorption of all sterols, including cholesterol and plant and
      shellfish sterols, and (b) impaired ability to excrete sterols into bile.
      Patients with this disease have expanded body pools of cholesterol and very
      elevated plasma plant-sterol species and frequently develop tendon and tuberous
      xanthomas, accelerated atherosclerosis, and premature coronary artery disease. In
      previous studies, we have mapped the STSL locus to human chromosome 2p21.
      Recently, we reported that a novel member of the ABC-transporter family, named
      "sterolin-1" and encoded by ABCG5, is mutated in 9 unrelated families with
      sitosterolemia; in the remaining 25 families, no mutations in sterolin-1 could be
      identified. We identified another ABC transporter, located <400 bp upstream of
      sterolin-1, in the opposite orientation. Mutational analyses revealed that this
      highly homologous protein, termed "sterolin-2" and encoded by ABCG8, is mutated
      in the remaining pedigrees. Thus, two highly homologous genes, located in a head
      to-head configuration on chromosome 2p21, are involved as causes of
      sitosterolemia. These studies indicate that both sterolin-1 and sterolin-2 are
      indispensable for the regulation of sterol absorption and excretion.
      Identification of sterolin-1 and sterolin-2 as critical players in the regulation
      of dietary-sterol absorption and excretion identifies a new pathway of sterol
      transport.

PMID- 11452360
TI  - Functional complementation of a genetic deficiency with human artificial
      chromosomes.
AB  - We have shown functional complementation of a genetic deficiency in human
      cultured cells, using artificial chromosomes derived from cloned human genomic
      fragments. A 404-kb human-artificial-chromosome (HAC) vector, consisting of 220
      kb of alphoid DNA from the centromere of chromosome 17, human telomeres, and the
      hypoxanthine guanine phosphoribosyltransferase (HPRT) genomic locus, was
      transferred to HPRT-deficient HT1080 fibrosarcoma cells. We generated several
      cell lines with low-copy-number, megabase-sized HACs containing a functional
      centromere and one or possibly several copies of the HPRT1 gene complementing the
      metabolic deficiency. The HACs consisted of alternating alphoid and nonalphoid
      DNA segments derived only from the input DNA (within the sensitivity limits of
      FISH detection), and the largest continuous alphoid segment was 158-250 kb. The
      study of both the structure and mitotic stability of these HACs offers insights
      into the mechanisms of centromere formation in synthetic chromosomes and will
      further the development of this human-gene-transfer technology.

PMID- 11452361
TI  - A genomewide screen for autism susceptibility loci.
AB  - We report the analysis of 335 microsatellite markers genotyped in 110 multiplex
      families with autism. All families include at least two "affected" siblings, at
      least one of whom has autism; the remaining affected sibs carry diagnoses of
      either Asperger syndrome or pervasive developmental disorder. Affected sib-pair
      analysis yielded multipoint maximum LOD scores (MLS) that reach the accepted
      threshold for suggestive linkage on chromosomes 5, X, and 19. Nominal evidence
      for linkage (point-wise P<.05) was obtained on chromosomes 2, 3, 4, 8, 10, 11,
      12, 15, 16, 18, and 20, and secondary loci were found on chromosomes 5 and 19.
      Analysis of families sharing alleles at the putative X chromosomal linked locus
      and one or more other putative linked loci produced an MLS of 3.56 for the DXS470
      D19S174 marker combination. In an effort to increase power to detect linkage,
      scan statistics were used to evaluate the significance of peak LOD scores based
      on statistical evidence at adjacent marker loci. This analysis yielded impressive
      evidence for linkage to autism and autism-spectrum disorders with significant
      genomewide P values <.05 for markers on chromosomes 5 and 8 and with suggestive
      linkage evidence for a marker on chromosome 19.

PMID- 11452362
TI  - Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33.
AB  - Chordoma is a rare tumor originating from notochordal remnants that is usually
      diagnosed during midlife. We performed a genomewide analysis for linkage in a
      family with 10 individuals affected by chordoma. The maximum two-point LOD score
      based on only the affected individuals was 2.21, at recombination fraction 0, at
      marker D7S2195 on chromosome 7q. Combined analysis of additional members of this
      family (11 affected individuals) and of two unrelated families (one with 2
      affected individuals and the other with 3 affected individuals), with 20 markers
      on 7q, showed a maximum two-point LOD score of 4.05 at marker D7S500. Multipoint
      analysis based on only the affected individuals gave a maximum LOD score of 4.78,
      with an approximate 2-LOD support interval from marker D7S512 to marker D7S684.
      Haplotype analysis of the three families showed a minimal disease-gene region
      from D7S512 to D7S684, a distance of 11.1 cM and approximately 7.1 Mb. No loss of
      heterozygosity was found at markers D7S1804, D7S1824, and D7S2195 in four tumor
      samples from affected family members. These results map a locus for familial
      chordoma to 7q33. Further analysis of this region, to identify this gene, is
      ongoing.

PMID- 11452363
TI  - The D13S171 marker, misannotated to BRCA2, links the AS3 gene to various cancers.

PMID- 11452364
TI  - The autism genetic resource exchange: a resource for the study of autism and
      related neuropsychiatric conditions.

PMID- 11452365
TI  - [Lipid metabolism, features of nutrition and risk factors of ischemic heart
      disease in cohorts of Canadian Inuits and Taimyr Nganasans].
AB  - Lipids metabolism and blood lipid profiles in native populations of Northern Asia
      (Nganasans, n = 43) and Northern Canada (Inuits, n = 151) have been studied.
      Estimation of serum PUFA of omega-6 and omega-3 series in Nganasans testifies to
      shifting of their diet to "western" type. Three types of dietary patterns have
      been observed in inuits: traditional one (among age group of 40-69), "western"
      (among age group of 18-29) and intermediate, transitional (among age group of 30
      39). Age differences in concentrations of total cholesterol, summarized fraction
      of low density and very low density lipoproteins in Nganasans and Inuits were
      similar, however, Inuits had higher levels of blood lipids including HDL
      cholesterol. Concentrations of apoB lipoproteins were significantly higher in
      Inuits, however, apoA-1/apoB ratios were estimated as more than 1.0 in both
      groups and the differences were not significant. Correlation between fatty acid
      composition and lipid profiles in Inuits who followed traditional diet testify to
      non-atherogenic type of nutrition. Despite to favorable blood lipid profiles in
      Northern native population, hypercholesterolemia was found in 2% of Nganasans and
      10% of Inuits, while hypo-alpha-cholesterolemia was found in 25% Nganasans and in
      5% of Inuits. Thus, changes in dietary patterns of native populations of the Far
      North have a great influence on blood concentrations of PUFAs of omega-3 series.
      Changes in the dietary fatty acid composition are considered to be one of the
      possible reasons of dislipoproteinemia.

PMID- 11452366
TI  - [Effects of dietary fiber on some indices of the activity of the gastrointestinal
      tract in rats].
AB  - Now nobody doubts of necessity and importance of inclusion of vegetative food
      fibres (as the separately isolated biopolymers--lignin, cellulose, gemicellulose,
      pectine substances; in composition of a food fibres complex or introduction last
      in traditional products of nutrition) in a daily human diet. Is proved by
      experimental researches, that the investigated kinds of food fibres are non
      toxic, do not influence on internal structure, are well perceived by animals and
      can be recommended as the additive in a human diet.

PMID- 11452367
TI  - [Possibility of participation of bacterial factor in the correction of histamine
      metabolism in the body].
AB  - Microbial factor belongs a significant role in mechanisms of regulation of
      contents free histamine in the organism. Magnified amounts this mediator
      connected with the condition of microbial ecology, can stimulate a number of
      pathophysiological effects. This dictates need of further studying dug autoflora
      master in processes of accumulation free histamine in the organism and their
      correction.

PMID- 11452368
TI  - [Improvement of medical care of children during the prevention stage].
AB  - The article looks at the problem of the improvement of medical aid for children
      and emphasizes the importance of the transference of medical attendance. It gives
      a detailed account of the subject of the school age children nutrition and the
      possibility of the correction and dietary rehabilitation of children alimentary
      dependent states.

PMID- 11452369
TI  - [Study of the state of lipid peroxidation system: antioxidant protection during
      the use of soy oil in patients with ischemic heart disease and hypertension].
AB  - Usage of antisclerotic diet with PUFA n-3 from soy oil in patients with IHD and
      HBP resulted in positive dynamic of clinic manifestation, blood lipids and
      coagulogramms of the patients. The decrease of intensity of lipid peroxidation
      was also revealed. The results showed that soy oil may be recommended for
      preventive and treatment diets.

PMID- 11452370
TI  - [Characteristics of actual nutrition and health of children in regions of the
      Russian Federation].
AB  - In the article the problems of actual nutrition and state of Russian children
      health are considered. The carried out examinations of the vitaminous status have
      shown presence of a deficit of vitamins E, B1, B6, PP, and also calcium,
      phosphorus, iron lactate, zinc in daily ration of children. The inadequate
      organization of C-vitaminization of boiled food in children establishments, low
      supplying of learning schools by a hot food, insufficient use of products from
      suer milk, fish, juices, meat products, butter, vegetables, fruit, eggs in a
      nutrition of children is marked. In same of regions of Russia the inadequate
      nutrition organization of early age children is marked. The positive experience
      of areas (St.-Petersburg, Ul'yanovsk, Rostov, Smolensk, Kirov, Kurgan, Samara
      region, Republic Buryatiya) on organization of children and juveniles nutrition,
      development of the regional programs on a children's food industry evolution, on
      providing of early age children by food stuffs, on improvement of a schoolboys
      nutrition, on improvement a nutrition of children in children's preschool
      establishments is analyzed. The positive experience of nutrition organization of
      children on an example of the Ryazan and Arkhangel'sk regions surveyed. The
      actual information about a vitaminization, quality and safety of children's
      nutrition, ready dishes in the organized collectives on data of 1999 are given.

PMID- 11452371
TI  - [Effects of a diet including linseed oil on clinical and metabolic parameters in
      patients with type 2 diabetes mellitus].
AB  - It was investigated the influence of a diet supplemented with PUFA omega-3
      (linseed oil) on dynamic of basal and postprandial glycemia, blood pressure,
      lipid levels, parameters of lipid peroxidation in 60 patients with non-insulin
      dependent diabetes mellitus. Linseed oil was used as a dietary supplement of PUFA
      omega-3. The results indicated that a diet supplemented with linseed oil (17.5
      g/day) did not increase the effect of dietary therapy in correction of glycemia,
      hypertension and atherogenic lipid levels. It was not the activation of lipid
      peroxidation.

PMID- 11452372
TI  - [Immunomodulating activity of thymogen in acute pancreatitis].
AB  - Immunity system parameters were explored at 48 persons with diagnosis of acute
      pancreatitis (AP) and at 36 practically healthy persons (donors). At AP diseased
      were found declinations in immunity system especially at the side of immunity T
      cell link. Including of tymogen in complex treatment at the dose 0.5-0.8 mg for
      the treatment course at AP diseased was having immune correcting action and
      leadind to positive dynamics of clinical changes. It was observed elimination of
      T-cell immune deficiency at AP diseased.

PMID- 11452373
TI  - [Organization of State sanitary inspection of food products from genetically
      modified sources].

PMID- 11452374
TI  - [Mycotoxins in spices].
AB  - Since antiquity, spices have been used for flavoring foods and beverages and for
      medication. They play an important role in the national economy of several of the
      producing, exporting and importing countries. Tropical climatic conditions under
      which spices are grown offer a favorable environment for the fungal and mycotoxin
      contamination. This review summarized information from 44 reports on the
      occurrence of mycotoxins (aflatoxins, ochratoxins zearalenone, fumonisins,
      trichothecenes) and their levels in different spices. Aflatoxins which are highly
      carcinogenic compounds, produced by A. flavus and A. parasiticus, are the leading
      toxins present in red peppers (paprika, chilli, cayenne) nutmeg, mustard, ginger,
      black and white peppers, coriander. Ochratoxins have been reported also as a
      natural contaminants in many spices. Although the levels of mycotoxins are
      generally low when compared with other food products, the testing of spices
      (imported and domestic) by regulatory agencies seems to be in need of expansion.

PMID- 11452375
TI  - [New food substitute (sweetener)--erythritol].

PMID- 11452376
TI  - [Conditions of actual nutrition and immunological reactivity of women students in
      different seasons].
AB  - On investigating of 60 healthy female students with use of a questionnaire
      method, it was found out what amount of basic nutrients, such as: proteins
      (especially those of animal origin), animal fats, hydrocarbons, vitamins (C, B1,
      B2, B6) mineral elements (calcium, potassium, magnesium and phosphorus) in
      students nourishment was lower in the spring than in the fall. Both in the spring
      and in the fall this amount was not appropriate for recommended physiological
      nourishment standards. On investigating of immunological reactivity of these
      students season's fluctuations for some indexes of cellular and humoral immunity
      were found. Lowering of T-lymphocytes lever together with lowering of blood
      immunoglobulines (especially those of G-calss) and lowering of lever of
      immunological complexes, circulating in the blood in spring comparing to the fall
      combinated with growth of B-lymphocytes lever.

PMID- 11452377
TI  - Crystallization and some properties of glutamate dehydrogenase from rat liver.
AB  - 1. Glutamate dehydrogenase (L-glutamate:NAD(P) oxidoreductase, EC 1.4.1.3) from
      rat liver has been crystallized with a method carefully avoiding all denaturating
      agents. A 236-fold purification was achieved at a yield of 20%. The specific
      activity was 185 units/mg protein. The enzyme was homogeneous by analytical zone
      electrophoresis and sedimentation studies. The s0(20),w value was 13.2. 2.
      Sedimentation studies in the analytical ultracentrifuge and the behaviour of the
      enzyme in the disc-electrophoresis revealed that glutamate dehydrogenase from rat
      liver did not undergo a reversible association-dissociation reaction as reported
      of glutamate dehydrogenase of nearly all other mammalians. 3. Using antibodies
      prepared against crystalline bovine liver glutamate dehydrogenase, no
      immunological differences between the rat and the bovine liver enzyme could be
      observed.

PMID- 11452378
TI  - Fractionation of pepsin-digested, denatured collagen. III. Characterization of
      the small fragments.
AB  - The survey of the fragments obtained from pepsin-digested, denatured rat tail
      tendon collagen is completed. Three additional fragments could be renatured and
      two of them (490 A and 670 A) were located in tropocollagen by electron
      microscopy. Data are given on the amino acid compositions of the various
      fractions. Certain fragments probably originated from the associated non
      collagenous material belonging to the "acidic structural proteins".

PMID- 11452379
TI  - Heat denaturation of human high density lipoproteins and chylomicrons.
AB  - 1. The objective of this investigation was to determine whether structural
      differences between apolipoproteins could be detected by heat denaturation. 2.
      The apoproteins of human serum high density lipoprotein (HDL2, d = 1.070-1.125
      and HDL3, d = 1.125-1.21 g/ml), their major polypeptide constituents (R-Thr and R
      Gln), and apochylomicrons were investigated. 3. Heat denaturation was found to be
      reversible in the temperature range from 20 to 80 degrees. 4. The thermodynamic
      parameters of heat denaturation delta F, delta H, delta S and delta Cp were
      calculated on the basis of a single transition from the "native" to "denatured"
      state for apo-HDL2, apochylomicrons, R-Thr and R-Gln; for apo-HDL3 these
      parameters were calculated on the basis of two transitions. 5. The thermodynamic
      parameters, with the exception of delta F, which describe heat denaturation of
      high density apolipoprotein, of high density apolipoprotein polypeptides and of
      apochylomicrons were found to be similar on a molar basis and to have
      approximately the same values as the thermodynamic parameters which describe heat
      denaturation of non-lipid binding proteins; on a weight basis differences were
      apparent between the apolipoproteins and the polypeptides or non-lipid binding
      proteins.

PMID- 11452380
TI  - Free-flow electrophoresis of proteins in phenol-containing solvents at various pH
      values.
AB  - 1. Several proteins were found to migrate when subjected to free-flow
      electrophoresis in buffered phenol-ethanediol-water (3:2:3, w/v/v) solvent
      mixtures. Mobility of these proteins changed with changing pH (apparent) values
      of this medium. A pH value of zero mobility for each individual protein could be
      estimated. 2. Founded on these observations, a high-voltage electrophoresis
      method in free-flowing buffer films was worked out. The method as presented here
      was particularly suitable for the separation of proteins on a preparative scale.
      Application of this and other protein fractionation techniques in dissociating
      media for the investigation of structural and other insoluble proteins was
      discussed.

PMID- 11452381
TI  - Flow dichroic spectra of tobacco mosaic virus and their protein assemblies.
AB  - Ultraviolet flow dichroisms of tobacco mosaic virus (TMV), TMV-RNA and TMV
      protein were measured using three strains of TMV. 1. Large positive dichroisms
      were observed with three strains of TMV, namely ordinary, bean form of bean, and
      tomato strains (TMV-OM, TMV-B and TMV-T, respectively) at about 255, 276, 284 and
      290 nm. The positive dichroisms were confirmed with reconstituted protein
      assemblies of TMV-OM and TMV-B at about 276, 284 and 290 nm where tyrosine and
      tryptophan residues of these proteins contribute. These results show that the
      electronic transition moments of their base groups and aromatic groups are nearly
      parallel to the polymer axis. It is suggested that there is a strong interaction
      between the base groups of RNA and aromatic groups of amino acid residues in TMV.
      2. A small negative dichroism was observed near 296-300 nm with intact TMV-OM and
      TMV-T and with the reconstituted protein polymer of TMV-OM. But negative
      dichroism was not observed either with the intact virus or the protein assembly
      of TMV-B. 3. Isolated RNA from TMV-OM, TMV-B and TMV-T showed no dichroism. The
      configuration of RNA in TMV appears to be imposed on it by its packing with the
      protein.

PMID- 11452382
TI  - Nitration of the tyrosine in histone F1 in salt solutions and in F1-polyanion
      complexes.
AB  - The reaction of histone F1 with tetranitromethane was used to study the
      environment of the single tyrosine residue in the molecule. It was found that at
      a 10-fold molar excess of tetranitromethane over tyrosine approx. 40 min were
      needed to convert 85% of the tyrosine residues to nitrotyrosine. The rate and
      extent of nitration of F1 in dilute salt solutions was used as a reference
      against which the rate and extent of nitration under conditions known to affect
      the conformation of F1 was measured. In 1.0 M NaCl solutions the rate of
      nitration decreased, suggesting that the presence of salt may cause a
      conformational change in the tyrosine containing region of the histone. When the
      histone is complexed with polyanions such as DNA, RNA or poly-L-glutamic acid the
      accessibility of the tyrosine to nitration is markedly reduced. The results
      indicate that upon association with polyanions the non-cationic, tyrosine
      containing, region in F1 undergoes a conformational change or alternatively, this
      tyrosine containing region is tightly associated with the polyanion.

PMID- 11452383
TI  - Obviation of destructive action of 0.2 M NaOH on proteins during arginine
      modification with cyclohexanedione by use of 0.1 M triethylamine as solvent.
AB  - The use of 0.2 M NaOH as a solvent for modification of arginine residues by 1,2
      cyclohexanedione in disulfide containing proteins is destructive to the disulfide
      bonds. Modification can be conveniently done in 0.1 M triethylamine (pH 10.9)
      without any deleterious effect. Lysozyme was found to retain all its enzymic
      activity in 0.1 M triethylamine (pH 10.9) whereas complete loss of activity took
      place in 0.2 M NaOH.

PMID- 11452384
TI  - Carboxyl-terminal residues of mammalian fibrinogen and fibrin.
AB  - The carboxyl-terminal residues of mammalian fibrinogens of six different species
      and the chain peptides, alpha(A), beta(B) and gamma, isolated from these
      fibrinogens were determined by hydrazinolysis, digestion with carboxypeptidases
      and selective tritium labelling. The C-terminal ends of bovine fibrinogen and
      fibrin were identified as proline and valine, in the molar ratio of approximately
      1:2. Proline was identified as the C-terminus of the alpha(A)-chain, and C
      terminal valine was found on both the beta(B)- and gamma-chains. On
      hydrazinolysis after selective tritium labelling of fibrinogen, radioactive C
      terminal valine was also identified. The same C-terminal ends as those of bovine
      fibrinogen were found on the corresponding chain peptides isolated from sheep
      fibrinogen. The C-terminal residues of all the chain peptides of human and horse
      fibrinogens, however, were valine. In hog and dog fibrinogens, proline was
      identified at the C-termini of the alpha(A)-chains, and C-terminal valine and
      isoleucine were found on the beta(B)- and gamma-chains, respectively. Thus, the C
      terminal amino acid residues of the fibrinogens of all mammalian species tested
      were very similar. It should be noted that hydrophobic amino acids, like
      isoleucine, valine and proline, are mainly located in the C-terminal ends of all
      three chain peptides in the fibrinogen molecule.

PMID- 11452385
TI  - Isolation and characterization of human foetal alpha-globulin (alpha 1F) from
      foetal and hepatoma sera.
AB  - The alpha 1F present in human foetal sera and the serum from a patient with
      hepatocellular carcinoma was isolated by immune precipitation using rabbit anti
      alpha 1F. After labelling with 125I, some physicochemical properties of alpha 1F
      were investigated. The molecular weights of 125I-labelled alpha 1F isolated from
      foetal and hepatoma sera were 61,000 and 63,000, respectively. The protein was
      not dissociated in 6 M guanidine after complete reduction, showing that it
      contains a single peptide chain.

PMID- 11452386
TI  - Number and types of peptide chains in thyroglobulin: tryptic peptides of
      noniodinated hog thyroglobulin.
AB  - In order to identify the number and types of peptide chains in thyroglobulin,
      noniodinated 19-S thyroglobulin obtained from goitrogen-treated hogs was
      exhaustively digested with trypsin (EC 3.4.4.4) after reduction and S
      carboxymethylation. The digestion mixture was preliminarily separated into 30
      fractions on Sephadex G-100 or G-15 and SE-Sephadex columns. The number of
      various tryptic peptides contained in each fraction was determined on peptide
      maps, where spots were detected with ninhydrin for total peptides and with each
      specific reagent for arginine, histidine or tyrosine-containing peptides. The
      number of total peptides observed in most of the fractions was estimated to be
      half the number of lysine plus arginine residues found in each fraction per mole
      of thyroglobulin, and the number of specific peptides was also close to half the
      number of each specific amino acid. These findings imply that thyroglobulin has 2
      fold symmetry in the structure at the level of tryptic fragments and thus
      probably at the level of intact peptide chains.

PMID- 11452387
TI  - Chimpanzee foetal haemoglobin: structure and heterogeneity of the gamma chain.
AB  - The amino acid compositions of soluble tryptic and chymotryptic peptides of the
      gamma chain of chimpanzee foetal haemoglobin have been determined. The peptides,
      accounting for all 146 residues of the gamma chain, were found to be identical in
      composition to the corresponding human gamma chain peptides. As in man, position
      gamma 136 can be occupied by glycine (G gamma chain) as well as alanine (A gamma
      chain). The ratio of G gamma to A gamma chains in the infant chimpanzee is
      approx. 2:1, and in the adult approx. 1:2.

PMID- 11452388
TI  - Analysis of the principal g-tensors in single crystals of ferrimyoglobin
      complexes.
AB  - This paper describes a method of determining the directions of the principal axes
      of the g-tensors in single crystals from measurements of the g-value variation in
      three crystalline planes (ab, bc*, ac) and of the principal values of g-tensors.
      Measurements of paramagnetic resonance spectra of ferrimyoglobin (Mb(Fe3+))
      complexes (Mb(Fe3+).CN-, .N3-, .imidazole(Im.) and .OCN-) in single crystals
      provided detailed information on the electronic state of the Fe3+. The direction
      of the z axis in Mb(Fe3+).CN-, .N3- and .Im. is not parallel to that in
      Mb(Fe3+).H2O, which has been used as the haem normal, where the z axis is one of
      the principal axes of the g-tensors corresponding to the maximal (in low-spin
      state of Fe3+ in haem) or minimal (in high-spin state of Fe3+ in haem) g-value.
      In Mb(Fe3+).OCN-, however, which is in thermal equilibrium between high-spin and
      low-spin states, the directions of the z axis in both states seem to be
      perpendicular to the haem plane. The direction of the x axis is not parallel to
      the plane of the linked histidine ring.

PMID- 11452389
TI  - The extraction of polymeric collagen from biopsies of human skin.
AB  - 1. Medium sized biopsies (100 mm2) of human skin from 14 subjects yielded
      sufficient polymeric collagen for depolymerisation and ultrastructural
      investigations. 2. The yields obtained from one skin specimen by the alpha
      amylase, EDTA and lyotropic relaxation (water) methods of extracting polymeric
      collagen are similar. 3. The responses to depolymerisation treatments of the
      three polymeric collagen samples extracted by each of the three methods from one
      skin specimen are cross-correlated. There are however electron microscopical
      differences between the three polymeric collagen samples. 4. The results show
      that it feasible to study the polymeric collagen of normal and diseased human
      skin from medium sized biopsies.

PMID- 11452390
TI  - Racemization of alpha-melanotropin.
AB  - Racemization of the amino acid residues of alpha-melanotropin was measured after
      exposure of the peptide to alkali for various lengths of time. Rates of
      racemization were then compared to the rate of transformation by alkali of alpha
      melanotropin into a hormone with prolonged melanotropic activity. When in vitro
      prolongation became maximal, serine, methionine, histidine, phenylalanine and
      arginine were racemized 50-70%, glutamic acid, tyrosine and tryptophan 30-40% and
      lysine, proline and valine 10% or less. Racemization of a particular amino acid
      residue in alpha-melanotropin could not be associated with induction of
      prolongation of activity. Rather, partial racemization at multiple sites in the
      molecule seems almost as effective as extensive or total racemization of a single
      residue in producing a hormone with prolonged biological effects.

PMID- 11452391
TI  - Preparation and immunoreactive properties of monoiodinated angiotensin labelled
      at high specific activity.
AB  - Monoiodinated angiotensin II at a specific activity in the order of 1 C/mg can be
      prepared with high yields by controlling the pH of iodination and can be purified
      on G-25 Sephadex. The fractions from the head to the centre of the single peak of
      radioactivity obtained by gel filtration of the iodination mixture contain pure
      monoiodinated angiotensin. The monoiodinated derivative shows an immunoreactivity
      very close to that of the native hormone; in contrast, the diiodinated derivative
      has a low immunoreactivity and its use as a tracer results in a loss of
      sensitivity in the radioimmunoassay of angiotensin II. It is suggested that the
      use of the monoiodinated derivative in pure form should be recommended whenever a
      small hormonal polypeptide labelled at high specific activity is to be prepared
      for radioimmunoassay purposes.

PMID- 11452392
TI  - [Effect of pH on the physico-chemical and immunologic properties of rabbit
      antibodies].
AB  - The effects of an incubation at low pH (during 20 h at 37 degrees) on the
      antibody activity and anticomplementary activity of rabbit IgG have been studied.
      Modifications have also been examined by physicochemical methods. The properties
      of rabbit anti-sheep red cell IgG are not modified by incubation at pH values
      between 7.4 and 4.0 during 20 h at 37 degrees. Below pH 4 a decrease of hemolytic
      activity is apparent concomitant with an important increase of the agglutinating
      activity. This phenomenon is due to the formation of polymers from native IgG. At
      pH values below 3.8 the anticomplementary activity of a nonspecific IgG decreases
      rapidly. One observes an increase of optical rotation, a finding which is
      compatible with the appearance of heavier compounds with sedimentation
      coefficients of 9.5 and 11.5 S, probably dimers of native IgG. The increase of
      optical rotation is partially reversible when the pH is readjusted to 7.4. The
      use of starch-gel and immunoelectrophoresis has shown the appearance of compounds
      with higher mobility which are closely related to a peptide (PEP III') which was
      isolated from a peptic hydrolysate of rabbit IgG. The decrease of
      anticomplementary activity of nonspecific IgG seems to be closely related to the
      liberation of PEP III'.

PMID- 11452393
TI  - Studies on a cytochrome oxidase antibody. III. Cross reactivity.
AB  - A rabbit serum antibody induced in response to injections of beef heart
      cytochrome oxidase has been demonstrated to be capable of the quantitative
      precipitation of a solubilized rat liver cytochrome oxidase.

PMID- 11452394
TI  - [Dissociation of thyroglobulin by tetraphenylborate ion].
AB  - Purified bovine and ovine thyroglobulins (19 S) are partially dissociated into 12
      S subunits after treatment with sodium tetraphenyl borate. The extent of
      dissociation obtained by sodium tetraphenyl borate or sodium dodecyl sulfate
      treatment is the same. The electrophoretic mobilities on acrylamide gels of
      sodium tetraphenyl borate-resistant molecules and of native thyroglobulin are
      identical. Sodium dodecyl sulfate-resistant molecules move more slowly than the
      native protein.

PMID- 11452395
TI  - Acute and subchronic neurotoxicological evaluation of tetrahydrofuran by
      inhalation in rats.
AB  - Groups of adult male and female rats received exposure to tetrahydrofuran (THF)
      vapor by inhalation in acute or subchronic exposure scenarios. Acute exposure
      concentrations were 0, 500, 2500, or 5000 ppm for 6 hr. Evaluations conducted
      immediately after exposure included clinical observations, motor activity
      assessments (MA), and a battery of functional tests (FOB) designed to reveal
      nervous system dysfunction. During exposure to 2500 and 5000 ppm, rats had a
      diminished or absent startle response to a punctate auditory alerting stimulus.
      Following exposure to 5000 ppm, male and female rats were lethargic, exhibited
      abnormal gait or mobility, and splayed rear feet. Lethargy and splayed rear feet
      were also observed in females exposed to 2500 ppm. During the subsequent FOB,
      males exposed to 5000 ppm had a lower incidence of palpebral closure, higher
      incidences of slow or absent righting reflex, and a biphasic pattern of reduced
      motor activity followed by increased motor activity. Females exposed to 5000 ppm
      had increased incidences of palpebral closure in the open field, increased
      incidences of slow or absent righting reflex, and decreased motor activity.
      During the 14-week subchronic exposure series, daily THF exposure concentrations
      were 0, 500, 1500, or 3000 ppm, and neurobehavioral evaluations occurred on non
      exposure days at approximately monthly intervals. Diminished startle responses to
      an auditory alerting stimulus were observed during exposure to 1500 or 3000 ppm;
      however, repeated exposures did not cause additional neurobehavioral or
      pathological effects. This pattern of effects is suggestive of transient
      sedation. Despite daily reinstatement of acute sedative effects during repeated
      exposure with up to 3000 ppm, THF did not produce any persistent or cumulative
      effects on nervous system structure or function. The demonstrated no-observed
      effect level of THF for both acute and subchronic exposure was 500 ppm.

PMID- 11452396
TI  - Inhalation toxicity of cyclooctadiene in rats.
AB  - Groups of 20 male Crl:CDBR rats each were exposed, whole-body, for six hours/day,
      for a total of nine exposures over a two-week period to concentrations of 52,
      150, or 500 ppm of 1,5-cyclooctadiene vapor. A control group of 20 male rats was
      exposed simultaneously to houseline air. Ten rats per group were used for
      standard toxicological evaluations and ten rats per group for neurotoxicity
      testing. In the standard toxicology group, at the end of the exposure period,
      blood and urine samples were collected for clinical analyses, and five rats per
      group were sacrificed for pathologic examination. After a two-week recovery
      period, the surviving rats in the standard groups were also given clinical and
      pathological examinations. The neurotoxicity group was given a functional
      observational battery (FOB) test and motor activity evaluations after the fourth
      and ninth exposures. In addition, six of ten neurotoxicity rats per exposure
      group were given neuropathology evaluations at the end of the exposure period. In
      rats exposed to 500 ppm of 1,5-cyclooctadiene there was an absence of alerting
      response toward the end of the daily six-hour exposures. These rats appeared to
      recover within 1/2 hour after exposure. This effect was not observed in the other
      test groups. The FOB evaluation showed an increase in the number of rats found
      sleeping in the 500 and 150 ppm groups compared to controls after the last
      exposure, but there were no treatment-related effects in the motor activity
      evaluation. Since there were no other neurobehavioral findings and no toxicity
      findings in the 150 ppm group, the sleeping behavior in the 150 ppm group was
      considered insufficient evidence of an adverse effect. Clinical laboratory
      evaluation of the 500 ppm group showed urinary pH decreases at the end of the
      exposure period but not after the two-week recovery period. There were no other
      toxicologically important changes in urine analysis, hematologic, or blood
      chemistry evaluations attributable to the test compound. Histologic effects were
      found in the nose and kidneys of rats in the 500 ppm group. There was a mild
      degeneration/necrosis of nasal olfactory epithelium observed immediately after
      the exposure period and a mild degeneration/regeneration in this area observed
      after the two-week recovery. In addition, there were increased kidney weights in
      the 500 ppm group immediately after exposure along with increased hyaline
      droplets in the kidneys. These effects were reversible after the two-week
      recovery period. There were no significant nasal or kidney effects observed in
      the 150 and 52 ppm test groups, and no other organ weight or histological effects
      attributable to the test compound observed in the standard toxicology groups at
      either evaluation time. The neuropathologic evaluation showed only one minor
      lesion in one 500 ppm-group rat and this was not considered to be attributable to
      exposure to 1,5-cyclooctadiene. Based on the decreased alerting response observed
      in rats during exposure at 500 ppm, and on the effects observed in the nose,
      kidney, and urine in rats at this concentration, the no-observed-adverse-effect
      (NOAEL) level in this study was considered to be 150 ppm.

PMID- 11452397
TI  - Evaluation of the immunomodulatory effects of the disinfection by-product, sodium
      chlorite, in female B6C3F1 mice: a drinking water study.
AB  - Sodium chlorite is an inorganic by-product of chlorine dioxide formed during the
      chlorination of drinking water. Relatively little is known about the adverse
      health effects of exposure to sodium chlorite in drinking water. In this study,
      we evaluated sodium chlorite's immunomodulatory properties using female B6C3F1
      mice and a panel of immune assays that were designed to evaluate potential
      changes in innate and acquired cellular and humoral immune responses. Female
      B6C3F1 mice were exposed to sodium chlorite in their drinking water (0, 0.1, 1,
      5, 15, and 30 mg/L) for 28 days, and then evaluated for immunomodulation.
      Overall, minimal toxicological and immunological changes were observed after
      exposure to sodium chlorite. Increases in the percentages of blood reticulocytes,
      and the relative spleen weights were both observed at different sodium chlorite
      treatment levels; however, these increases were not dose-dependent. An increasing
      trend in the number of spleen antibody-forming cells was observed over the range
      of sodium chlorite concentrations. This increase was not, however, significant at
      any individual treatment level, and was not reflected by changes in serum IgM
      levels. A significant increase (26%) in the total number of splenic CD8+ cells
      was observed in mice treated with 30 mg/L of sodium chlorite, but not at the
      other concentrations. Splenic mixed leukocyte response and peritoneal macrophage
      activity were unaffected by sodium chlorite. Lastly, exposure to sodium chlorite
      did not affect natural killer cell activity, although a decrease in augmented
      natural killer cell activity (42%) was observed at the lowest sodium chlorite
      treatment level. These results suggest that sodium chlorite, within the range 0.1
      30 mg/L, produces minimal immunotoxicity in mice.

PMID- 11452398
TI  - Developmental toxicity study of tetramethylurea (TMU) in rats.
AB  - The developmental toxicity of tetramethylurea (TMU) was assessed in rats by
      inhalation exposure of the test material over days 6-20 of gestation. Groups of
      25 mated female Crl:CD BR rats were exposed whole-body for 6 hours/day to
      concentrations of either 0, 2, 20 or 100 ppm TMU. The dams were euthanized on day
      21 and the offspring were weighted, sexed, and examined for external, visceral,
      and skeletal alterations. Maternal toxicity was demonstrated at both 20 and 100
      ppm. Maternal body weights, weight changes, and food consumption were
      statistically significantly reduced at these concentrations; effects were more
      pronounced at 100 ppm. There was evidence of developmental toxicity only at 100
      ppm. The only finding was a decrease in mean fetal weight. No fetal malformations
      or variations occurred in fetuses derived from rats exposed to all 3 test
      concentrations (up to 100 ppm). The maternal no-observed-effect-level (NOEL) was
      2 ppm, the fetal NOEL was 20 ppm. Thus, TMU was not considered to be uniquely
      toxic to the rat conceptus.

PMID- 11452399
TI  - Effect of 4-vinylcyclohexene on micronucleus formation in the bone marrow of rats
      and mice.
AB  - This study was conducted to evaluate the potential of 4-vinylcyclohexene (VCH) to
      induce micronuclei in the bone marrow of mice and rats. Male and female Crl:CD BR
      (Sprague-Dawley) rats and B6C3F1/CrBR mice were exposed to VCH 6 hr/day for 2
      days or for 13 weeks. In the 2-day study, mice were exposed by inhalation to 0,
      250, 500, or 1000 ppm, and rats were exposed to 0, 500, 1000, or 2000 ppm. In the
      13-week study, mice were exposed to 0, 50, 250, or 1000 ppm, and rats were
      exposed to 0, 250, 1000, or 1500 ppm. In each study, a separate group of mice was
      exposed to 1000 ppm 1,3-butadiene (BD) so that a comparison could be made between
      the two compounds. Likewise, cyclophosphamide was also included for rats as a
      positive control. Bone marrow was collected from VCH-exposed animals
      approximately 24 h and 48 h after the final exposure. There were no statistically
      significant increases in micronucleatedpolychromatic erythrocytes (MN-PCEs) among
      VCH-treated mice and rats at any dose level or sampling interval at either 2-days
      or 13-weeks. Also, no statistically significant differences in the polychromatic
      erythrocytes (PCE) to normochromatic erythrocytes (NCE) ratios were observed in
      any of the VCH-treated mice and rats compared to air-exposed animals. As
      expected, both the butadiene-treated mice and the cyclophosphamide-treated rats
      showed significantly more MN-PCEs than the control animals.

PMID- 11452400
TI  - Apoptosis induction and cell cycle perturbation in established cell lines by
      peroxysomicine A1 (T-514).
AB  - Peroxysomicine A1, a novel potential anticancer compound induced cell death in
      established cell lines and in a primary culture of rat neonatal cardiomyocytes.
      Non-transformed cells are less sensitive to the compound than transformed cell
      lines. Fluorescent microscopy of dying cells stained with DNA-specific dyes
      revealed chromatin condensation and nuclear fragmentation as well as membrane
      blebbing characteristic of apoptosis. Flow cytometry of cells treated with
      peroxysomicine A1, demonstrated appearance of cells containing less than 2C DNA,
      that indicated degradation of nuclear DNA, another hallmark of apoptotic cell
      death. Z-VAD, a nonspecific caspase inhibitor, prevented DNA fragmentation but
      not cell death registered by permeabilization of cell outer membrane.
      Peroxysomicine A1 also inhibited proliferation of various cell lines. Flow
      cytometry analysis showed significant accumulation of dividing cells in G2/M
      phases of cell cycle indicating, most likely delay in G2. These results provide
      initial insight into the mechanisms of action of peroxysomicine A1 and suggest
      that peroxysomicine A1 is a potent inhibitor of cell proliferation and inducer of
      apoptosis and may be a useful antineoplastic chemotherapeutic agent.

PMID- 11452401
TI  - Computed tomography scanning in children: radiation risks.

PMID- 11452402
TI  - Nasopharyngeal carcinoma in Turkish children: review of 33 cases.
AB  - A retrospective and prospective analysis is reported of epidemiological,
      clinical, and therapeutic aspects of 33 children with nasopharyngeal carcinoma
      who were treated in a single institution over a period of 10 years. Twenty-three
      male and 10 female children ranging from 9 to 17 years were referred to our
      center. Histopathology was WHO type 3 carcinoma in 21, WHO type 2 in 8, WHO type
      1 in 1, and unclassified in 3 patients. Disease extent was T2a (n = 15), T2b (n =
      2), T3 (n = 11), and T4 (n = 5); N1 (n = 5), N2 (n = 12), and N3a (n = 16). Five
      patients had base of skull invasion. Four patients had M1 disease on admission.
      Four patients were treated with irradiation only. Three patients received
      neoadjuvant, 4 patients received adjuvant, and 22 patients received neoadjuvant +
      adjuvant chemotherapy in addition to radiotherapy. Patients received 50-72 Gy to
      the primary tumor and involved nodes and 45-50 Gy to uninvolved regions.
      Chemotherapy consisted of combinations of cisplatin, fluorouracil or Adriamycin,
      vincristine, and cyclophosphamide. Twenty-nine patients (88%) attained
      locoregional control. Overall, 10 patients died with progressive disease or
      infectious complications, and 2 patients are still receiving therapy. Three
      patients are still living with multiple metastases and stable disease. Eight
      patients were lost to follow-up. Twelve patients are alive without relapse 3 and
      63 months from diagnosis. Seven patients had 6 relapses at distant and 1 relapse
      at local site. The median time for first relapse was 8 months. Overall, the 5
      year survival rate was 63% and disease-free survival rate was 53%. Although the
      locoregional control rate is high, long-term survival rates will be the real test
      of the impact of chemotherapy. Further studies are needed to confirm the optimal
      combination of effective chemotherapeutic agents and radiotherapy.

PMID- 11452403
TI  - Mechanical complications related to indwelling central venous catheter in
      pediatric hematology/oncology patients.
AB  - Indwelling central venous catheters (CVC) are essential devices in the management
      of children with oncologic/hematologic diseases or following bone marrow
      transplantation. The authors report data on the mechanical complications observed
      in pediatric hematology/oncology patients, collected by a retrospective analysis
      of clinical records of 482 patients in whom 567 indwelling central venous
      catheters had been inserted from January 1992 to December 1998 at the G. Gaslini
      Institute. During the study period, 52 episodes of mechanical complications (9%)
      were observed: mechanical obstruction (24 episodes), catheter dislocation (13),
      problems related to catheter material (12), and accidental removal (3). In 25
      cases removal and replacement of CVC was necessary for the treatment of
      complications, while medical treatment (thrombolytic-antithrombotic) was
      successful and well tolerated in 8. The study shows the importance of mechanical
      complications in children with indwelling CVC for hematologic or oncologic
      diseases. Moreover, the experience of administering a systemic low-dosage
      thrombolytic therapy demonstrates new prospects of reducing CVC replacement by
      restoring CVC viability.

PMID- 11452404
TI  - Effect of P-glycoprotein expression on outcome in the Ewing family of tumors.
AB  - This study was designed to determine the prognostic significance of multidrug
      resistance, mediated by P-glycoprotein (Pgp) expression, in Ewing sarcoma. The
      clinical and laboratory features, treatment protocol, and outcome of 75 patients
      with Ewing sarcoma or peripheral neuroectodermal tumor treated between 1972 and
      1997 were reviewed. Pgp expression was tested with the monoclonal antibody JSB-1.
      Thirty-four (64%) of the 53 tissue samples from untreated patients stained
      positive for Pgp. Progression-free and overall survival were 44 and 59%,
      respectively, in patients with negative findings, and 28 and 41% in those with
      positive findings; neither difference was significant. Of the 12 relapsed
      patients, 6 (50%) expressed more Pgp after chemotherapy than at diagnosis and 4
      (33%) expressed less. Within these subgroups, 5 out of 6 and 3 out of 4 died from
      the disease. No correlation was found between Pgp and known prognostic factors of
      Ewing tumors. Pgp expression is probably an intrinsic factor of Ewing tumors but
      has no correlation to prognosis.

PMID- 11452405
TI  - High-dose oral methylprednisolone therapy in childhood hemangiomas.
AB  - The authors report their experience with high-dose oral methylprednisolone
      therapy (HDMP) in 15 infants with complicated hemangiomas. The starting dose for
      methylprednisolone was 30 mg/kg/day for 5 days, then the dose was tapered
      gradually every 5 days to 20, 10, 5, 2.5, and finally to 1 mg/kg/day. Therapy was
      then stopped and the patients were followed. An initial response was evident in
      12 patients. Nine out of 12 responders showed regrowth signs. After regrowth, 4
      cases received prednisolone at doses between 1 to 5 mg/kg/day and 3 patients
      received a second course with HDMP as additional corticosteroid therapy. Overall,
      9 out of 15 cases were responders; very good and good responses were obtained in
      5, partial response in 4, and therapy failure in 5 cases. One child was not
      available for evaluation of response. A very rapid initial response was observed
      in subglottic and periocular hemangiomas. Side effects were not serious and
      resolved after discontinuation of treatment. Although the number of patients is
      small in this study, overall response rate with HDMP regimen seems not to be
      superior to the regimens that use lower doses (5 mg/kg/day), but it provides a
      high initial response rate and the duration of therapy is short. Therefore, it
      may be useful for treating hemangiomas that fail to respond with low doses,
      especially in centers with limited resources where other treatment modalities
      cannot be used at the moment.

PMID- 11452406
TI  - Guillain-Barre syndrome in a child with acute lymphoblastic leukemia.
AB  - A 4-year-old boy with acute lymphoblastic leukemia receiving maintenance
      treatment developed quadriparesis, facial palsy, difficulty in swallowing, and
      hypertension following a respiratory infection and candida septicemia.
      Examination of the cerebrospinal fluid was normal initially but later showed
      albuminocytologic dissociation, the characteristic finding of Guillain-Barre
      syndrome. Complete recovery occurred after treatment with intravenous
      immunoglobulin. Differential diagnosis of Guillain-Barre syndrome from
      vincristine toxicity in patients with leukemia and possible association with the
      infections are discussed.

PMID- 11452407
TI  - Carcinoid tumors of the appendix in children: two case reports and review of the
      literature.
AB  - Carcinoid is the most common tumor of the appendix. Reported incidence in
      pediatric population is 1 per 100,000 per annum. Clinical presentation like acute
      appendicitis is frequent, but carcinoid tumor can be an incidental finding during
      surgical procedures other than appendectomy. Size and depth of invasion are
      important prognostic criteria and tumors larger than 2 cm metastasize more
      frequently than smaller ones. Simple appendectomy is considered appropriate
      treatment, while right colectomy is indicated in tumor bigger than 2 cm. The
      authors report 2 cases of carcinoid tumors of the appendix in children, smaller
      than 2 cm treated with appendectomy alone, and disease free at follow-up.

PMID- 11452408
TI  - Delta-storage pool disease in infancy with absence of blood serotonin associated
      with psychomotor retardation.

PMID- 11452409
TI  - Autologous hematopoietic stem cell transplantation (AHSCT) as consolidation
      therapy for childhood acute myelogenous leukemia in 1st complete remission.

PMID- 11452410
TI  - Mycobacteria fortuitum central venous catheter-related bacteremia in an infant
      with renal sarcoma.

PMID- 11452411
TI  - [The detection of human papillomavirus 16, 18, 35 and 58 in cervical-uterine
      cancer and advanced degree of squamous intraepithelial lesions in Western Mexico:
      clinical-molecular correlation].
AB  - The purposes of this study were to estimate the infection frequency of Human
      Papilomavirus (HPV) and to identify the viral types in patients with diagnosis of
      uterine cervical cancer (UCC) and High Grade Squamous Intraepitelial lesions
      (HGSILs), and to correlate the molecular findings versus HPV infection suggestive
      clinical findings. Biopsies from 50 patients (37 HGSILs and 13 UCC)
      histopathologically diagnosed were studied. The presence of HPV were detected by
      means of the polymerase chain reaction (PCR) using consensus primers for types 6,
      11, 16, 18, 31, 33, 35, and 58 among others, as well as specific primers for some
      of them. The frequencies for HPV 16, 18, 33, 35, and 58 in HGSIL samples were
      24.3, 2.7, 0, 5.4 and 16.2% respectively. In UCC samples were 61.5, 7.7, 0, 0 and
      15.4% with significative differences only for HPV 16. Clinical findings
      (histologic, colposcopic and histopathologic), showed deficient diagnostic
      accuracy in the identification of HPV 16 in HGSIL, wich resulted less frequent
      and there is a high frequency of HPV. These results are similar to those
      previously described in our country and the other populations, with the exception
      of HPV16 in HGSIL, wich resulted less frequent and there is a high frequency of
      HPV 58 in our region. When analyzing clinical features with the presence of HPV
      DNA, we conclude that these are insufficient to discard or establish the
      possibility of HPV infection in patients with HGSIL's and UUC.

PMID- 11452412
TI  - [Perinatal results in patients with chronic hypertension at the National
      Institute of Perinatology].
AB  - There are many causes of Chronic Hypertension, and all can be present in pregnant
      women. The literature reports an incidence between 1-3%. The prognosis usually is
      favorable, if we have an excellent control of blood pressure along pregnancy. But
      the risks like abruptio placentae, fetal demise or fetal growth restriction have
      a greater incidence than in the health population, furthermore the superimposed
      preeclampsia increase notably the perinatal morbidity. The objective of this
      study is to determine the perinatal outcomes in women with chronic hypertension
      in the Instituto Nacional de Perinatologia. In the study we included 66 patients
      with chronic hypertension with age between 21-45 years old, and 54.4% had an age
      between 30-40 years. The evolution time of hypertensive disease was 5 years or
      less principally (71.2% of the patients).

PMID- 11452413
TI  - [Abdominal ectopic pregnancy resulting in living birth. Case report].
AB  - It's a report of a case of abdominal pregnancy of 36.3 weeks, at Hospital General
      de Mexico and obtained a male newborn child, weight 1.920 grammes, Apgar 2/5/7
      and Capurro of 36.3 weeks. Statistics, clinical manifestations and management are
      described.

PMID- 11452414
TI  - [Prevalence of breast self-examination in health workers. Factors associated with
      its correct performance].
AB  - OBJECTIVE: Determine the frequency of a breast self-examination (BSE), in health
      workers and the associated risk factors in its correct performance. MATERIAL AND
      METHODS: From January 24 to February 24, 2000, a transversal analytical study was
      performed in the workers of the General Hospital Zone number 32, of the IMSS in
      Minatitlan, Veracruz. 106 women were included, who verbally accepted to
      participate in the study. A self-administered survey was applied which contained
      variables of the use and performance of the BSE, social demographic variables,
      information about BSE, and positive health attitudes and faces with breast
      cancer. RESULTS: A total of 92 (86.8%) of the workers have performed an BSE at
      least once in their life; 46.2% performed it adequately and 53.8% did not perform
      the technique adequately. The variables: profession, high social economical
      level, nulliparous after 25 years old, users of contraceptives, having visited a
      gynecologist for breast clinical examination, and if a family member recommended
      to perform a BSE, were related with the use adequately of BSE (p < 0.05).
      CONCLUSIONS: The frequency of the use of a breast self-examination is high,
      however, it is not performed adequately by the majority of the women studied. Its
      correct execution is associated with the following variables: medical background
      doctor or nurse, well informed about BSE, family support and a positive health
      attitude. It is necessary to perform educational interventions so that the breast
      self-examination can be performed correctly.

PMID- 11452415
TI  - [Biomarkers in breast cancer with high over-expression of HER2 protein].
AB  - INTRODUCTION: The predictive value of the HER2 protein over-expression in order
      to the breast carcinomas response to dexorubicin and Herceptin therapy has been
      proved. DAKO Herceptest pretend to be a tool in the identification of patients
      for whose Herceptin might be an option. In one breast carcinoma serie studied in
      our laboratory we detected a high over-expression of HER2. Only four cases were
      recurrent tumors. OBJECTIVE: To characterize the breast carcinoma serie assayed
      with DAKO Herceptest by the expression of other prognostic or predictive markers
      (hormone receptors, Ki-67, p53, tumoral ploidy) that are routinely tested in our
      laboratory. MATERIAL AND METHODS: 97 consecutive mammary carcinomas recieved
      between July and October, 2000 in the ABC Medical Center's Surgical Pathology
      Department of Mexico City, were analyzed with DAKO Herceptest, and for
      estrogen/progesterone receptors, p53, Ki-67 and tumoral ploidy. RESULTS: We found
      HER2 over-expression in 46.3% of the cases tested. The 47.6% of this subgroup
      showed hormone receptors negative immunophenotype, 89.7% high cellular
      proliferation index (Ki-67), 72.5% of p53 expression, and tumoral aneuploidy in
      72.9%. CONCLUSIONS: The high expression of desfavorable prognostic and/or
      predictive factors for mammary carcinomas in the casuistic, suggest that the
      population in study have a particularly aggressive phenotype, where the over
      expression of HER2 protein results in concordance and it is not related with
      tumoral relapse.

PMID- 11452416
TI  - [Infertility treatment before assisted reproductive techniques].
AB  - The prevalence of infertility has increased in recent years, but the medical
      services to treat these problems are not available for most of the affected
      couples. The prognosis for fertility is important in order to determine the
      therapeutic capacity of each service, and to select the couples that could be
      treated at a primary level, or to send them to more advanced levels of
      reproductive technology. In practice, the infertility is treated in primary
      medical levels and the assisted reproductive technology is available only to a
      limited sector of the poblation. In general, the managed-care plans do not
      compensate directly for infertility treatments, but they are indirectly paying
      some therapeutic procedures for fertility.

PMID- 11452417
TI  - [Gamete laboratory. Determining factors of success in in-vitro fertilization].
AB  - The objective was to evaluate the gamete laboratory parameters that can to
      determine the possibility of achieving pregnancy in in vitro fertilization (IVF).
      A prospective study was carried in 196 patients undergone to conventional and
      oocyte donation IVF. After the evaluation of oocytes, embryos and the pregnancies
      was established that postmature oocytes were more frequently retrieved from
      patients that did not get pregnant. A good embryo morphology and principally the
      transfer of 4-cell embryos are common events in IVF. However, there were not
      significant difference in embryo parameters, number of blastomeres and embryo
      quality, between pregnant and not pregnant patients. In conclusion, it appear
      that bad oocyte quality has a negative effect over the possibility of achieving
      pregnancy. The number of blastomeres and embryo quality were not predictive of
      the possibility to get pregnant.

PMID- 11452418
TI  - [55 years ago. Endometriosis].

PMID- 11452419
TI  - [Spatial organizations of projections from area 18 to area 17 in the cat visual
      cortex].
AB  - Spatial distribution of efferent neuronal connections from area 18 to area 17 in
      the cat was investigated using the microiontophoretic horseradish peroxidase
      injections in a single cortical columns of area 17. The localization of
      rertogradely labelled cells in area 18 was determined and plots of labelled cells
      distribution in the plane of cortical surface, in the sagittal and in the frontal
      planes were done. It was shown that neuronal connections from area 18 to the
      single column in area 17 are elongated (in the cortical surface plane) in the
      same rostrocaudal direction, along the representation of visual field vertical
      meridian, just as the intrinsic horizontal connections in area 18. This findings
      demonstrate the spatial correspondence between efferent and intrinsic connections
      distributions in area 18. Such area 18 connections provide more detailed analysis
      of the vertical components of visual objects.

PMID- 11452420
TI  - [Changes in the rat cerebral cortex ultrastructure following peroral
      administration of manganese chloride].
AB  - The effect of 30 days treatment with MnCl(2).4H2O (50 mg/kg in doze) on neuron
      ultrastructure and interneuronal contacts of cerebral cortex frontoparietal area
      was studied in rat. The material for the research was taken on 1st (group 1) and
      4th (group 2) month of the experiment. Changes in neurons and cortex synapses
      were less significant than those in subcortical structures. In 1st group of
      experimental animals neurons displayed vacuolar system hyperplasia and swelling
      of a part of mitochondria. Changes in synapses were heterogenous from reduction
      of synaptic vesicles number and mitochondria swelling to degeneration after
      "dark" type. Despite the fact that intoxication with MnCl(2).4H2O was over,
      changes in cortical neurons in group 2 were significant although no cells with
      signs of reorganization were observed. In neuropil of rats from group 2 reduced
      number of synaptic vesicles as well as reorganized endings filled with amorphous
      osmiophilic content were encountered more often as compared to animals from group
      2.

PMID- 11452421
TI  - [Structural and quantitative characteristics of nuclear and screen-type formation
      in the amygdaloid body posterior region].
AB  - Cytoarchitecture and planimetry of structures of amygdaloid body posterior region
      were investigated in view of A.A. Zavarzin concepts on nuclear and screen-type
      centres of nervous system. Amygdaloid body was shown to be a complicated
      heterogeneous brain formation, the structure of which reflects both basic
      principles (nuclear and screen-type) of grey substance organization. Structural
      and quantitative characteristics of the amygdaloid body posterior region provides
      a confirmation for assumption that it is a nucleo-paleocortical brain component.

PMID- 11452422
TI  - [Cellular composition of the spinal ganglion following neonatal administration of
      capsaicin in rats].
AB  - Single administration of 100 mg/kg of capsaicine to newborn rats causes 30%
      decline in neurocyte number, decrease of average area of section neurocytes and
      dystrophic changes of majority of cells developing in a month. In 3 and 6 months
      60% decline of neurocyte number occur, increase of average neurocyte section area
      is retained, dystrophic changes in cells are less manifested. It was revealed
      through histogrammes that decline in neurocyte number was conditioned by
      reduction of fraction of small neurocytes. The results indicate the stable effect
      of chemical differentiation.

PMID- 11452423
TI  - [Ultrastructural changes in the aortic arch intima in rats with various
      resistance to emotional stress].
AB  - Experiments were performed on 24 male Wistar rats weighing 210 +/- 14 g.
      Depending on the activity in the open field test, all rats were divided into
      behaviorally active and passive subgroups. Water-immersion stress (2 hrs)
      followed by 2-hrs rest period was used as the model of acute emotional stress.
      Tissue samples from aortic ascending arch were taken from control and stressed
      rats immediately after decapitation and used for further electron microscopy. The
      number of micropinocytosis vesicles along the free and basal layers of the
      cytoplasm and the area of mitochondria were determined. Emotional stress was
      shown to intensify metabolic processes involving micropinocytosis vesicles
      between the aortic lumen and its wall. Passive rats display the most severe
      alterations induced by stress (damages of aortic endotheliocytes, partial
      regeneration of the plasmalemma by membranes of micropinocytosis vesicles, and
      decrease in the average area of mitochondria). Morphological equivalents of the
      initial stages of emotional stress-induced formation of fibrous changes in the
      aortic arch intima are believed to be found. Such changes can lead to the
      appearance of atherosclerotic patches.

PMID- 11452424
TI  - [Changes in microcirculation and their correction in patients with varicose veins
      and post-thrombotic syndrome].
AB  - Variety of disturbances of microcirculation can be stipulated by vasomotorial
      disfunction's of blood circulation in terminal vascular bed, changes of rheologic
      and coagulative characteristics of blood as well as morphological changes of
      structure of tissue and vessels of microcirculatory bed of destructed lower limb.
      In case of a varicose disease without complications changes of microvessels are
      considered to be compensatory adaptation. Patients suffering from a complicated
      type of varicose disease and post-thrombotic syndrome have "failure" of
      compensatory adaptation reaction. It results from significant functional
      disturbances of microcirculation and sudden morphological changes of structure of
      blood and lymphatic capillaries and tissue of a destructed lower limb.
      Correlative dependence can be found between degree of clinical evidences and a
      level of structural changes of microcirculatory bed. They are mostly significant
      in groups of patients having complicated varicose disease and post-thrombotic
      syndrome. It was shown that functional and morphological states of
      microcirculatory bed are of prognostic importance for estimation of effectiveness
      of operative interferences during diseases being analysed.

PMID- 11452425
TI  - [Anatomical variants of the rabbit thymus shape in the prenatal and postnatal
      ontogenesis].
AB  - Anatomical variants of three-dimensional shape of rabbit thymus were studied by
      method of plastic reconstruction. 11 age groups were used (94 animals in total).
      Individual and age variants of three-dimensional shape of thymus and its lobes,
      areas and character of their conjugation, spatial orientation and participant of
      different regions of the lobes in formation of the general level, lateral margin
      and cardiac notch were described. Dolychomorphic, mesomorphic and brachiomorphic
      variants of thymus shape were distinguished in rabbit. Significant participant of
      right lobe in formation of cardiac inlet was demonstrated.

PMID- 11452426
TI  - [Individual and topological characteristics of the lymph node structure depending
      on the body working capacity and functional reserve].
AB  - Two groups of dogs, one of which (14 animals) was a control one, and the other
      (10 animals) received the maximum loads in the form of running on the treadmill
      at the 15 km/hr speed, have been investigated. After the load the inquinal
      lymphatic node was extracted from the animals under the thiopental anaesthesia.
      The results of the lymphoid tissue morphometric analysis have demonstrated that
      the higher meanings of the reticular fibrae volumetric density in the cerebral
      substance were observed in animals with a high level of the working capacity (the
      time of running). The small lymphocyte population density ratio coefficient in
      the paracortical zone to the same value in germinative centres (K) was 2.25. The
      low meanings of the reticular fibrae volumetric density in the germinative
      centres are revealed in dogs with a low level of the working capacity. The K was
      1.59. In animals of this subgroup the cells, manifesting the phosphatase
      activity, are observed in great number in the medullar bands, which is
      corresponded with high meanings of the product of reaction of to alcaline
      phosphatase.

PMID- 11452427
TI  - [The cecum lymphoid structure in preterm and full term newborns].
AB  - Cellular content of lymphoid structures of coecum of full term and premature
      newborns was studied by means of quantitative and qualitative statistic analysis.
      Re-distribution of cells leading to decrease of cell concentration in lymph
      nodules at the portion overlooking lumen of the coecum and in contrary, to growth
      of cell number in nodule base was shown to occur within lymphoid nodules in terms
      from 7.5 months up to birth. By the moment of birth proportion of small
      lymphocytes in the nodules decreases while the proportion of medium lymphocytes
      and plasma cells grows higher. The number of granulocytes, macrophages and
      destroying cells increases as well. Blasts appear and the number of large
      lymphocytes grow higher. The studies demonstrate that development of lymphoid
      structures of premature newborns is not completed and thus they are less prepared
      to the contact with food antigens by the moment of birth.

PMID- 11452428
TI  - [Structure of the dog periodontium during milk and permanent occlusion].
AB  - The state of dog parodont during milk and permanent occlusion was studied by
      morphological methods in 8 animals. It was established that the structure of
      parodont of milk and permanent teeth has features characteristic for each type of
      occlusion. One of the important distinctions of parodont structure during milk
      occlusion is the presence of osteoclasts especially in the sites of root
      resorption. Close attachment of roots of milk teeth to follicles of permanent
      teeth should be taken into consideration in orthodontic correction of milk tooth
      position.

PMID- 11452429
TI  - [Qualitative and quantitative characteristics of fibers of the gastrocnemius and
      pectoral muscles of the chicken embryo].
AB  - The electron microscopic study shows that in 10 days chick embryo parenchymal
      elements of the gastrocnemius and pectoralis muscles are myotubes with sparse
      mitochondria, and that they do not differ morphologically. Up to the 18th day in
      ovo muscle fibers in the future oxidative muscle grow up faster than those in the
      future glycolytic one. There is no relation between the mitochondrial density and
      distribution within sarcoplasm and the capillary location but they are in good
      correlation with the myofibrillar parameters. As muscle fibers mature the energy
      delivery of myofibrils (mitochondria-to-myofibrils volume density ratio)
      increases due to mitochondrial density rather than their size.

PMID- 11452430
TI  - [Correlation-regression analysis of morphometric parameters of the tibial bone
      following osteotomy with experimental local infection].
AB  - Dynamics of morphometric parameters of ischemic disease and bone reparative
      regeneration were determined experimentally in 43 rats subjected to tibia
      resection with following infection with pathogenic S. aureus at terms from 3 to
      60 days. On 1st posttraumatic day mean parameters of ischemic in bones of rats
      alterations subjected to the operation in aseptic condition exceed that of rats
      from infected group; on later terms mean parameters of reactive and reparative
      changes in rats from infected group exceed that of rats from aseptic group;
      qualitative and quantitative differences in rats from both groups were reflected
      in differences of structure and intensity of correlation links and types of
      regression correlation between certain morphometric parameters of bone lesion.

PMID- 11452431
TI  - [Asymmetry of signs of finger dermatoglyphics, physical potential and physical
      qualities of a man].
AB  - Correlation between asymmetry of total signs of digital dermatoglyphs and general
      level of physical potential and basic physical qualities was studied. Highly
      qualified sportsmen were examined: men (231) and women (95) 20-38 yrs old; MPU
      students--men (106) and women (92) 17-20 yrs old; children with infantile
      cerebral paralysis, boys (12) and girls (42) 4-13 yrs old and parents of these
      children, man (12) and women (42) 25-48 yrs old. Variability of asymmetry of
      basic of digital dermatoglyfied was associated with sexual peculiarities of
      dominance of right or left hemisphere in functional asymmetry of brain.

PMID- 11452432
TI  - [Anatomical parameters determining somatotype of inhabitants of Southern regions
      of Russia of juvenile and first mature age in the norm and in scoliosis].
AB  - With the purpose of study of a degree of an expressiveness and character of
      mutual relation of fabric components of a soma (osteal, muscular and fatty) at
      the people of youthful and first mature age in norm and at a scoliosis I-II of a
      degree is surveyed on a method R.N. Dorohov (1994) 2756 men--inhabitants of the
      South of Russia. The received results specify that for the people with a
      scoliosis I-II of a degree are characteristic micro-(person of a female) and
      macrosomn (person of a male) types at the low contents of muscular and fatty
      masses of a body in a combination with grasilisation of a skeleton and prolate
      extremities. Taking into account a rather high degree of a hereditary
      determination of the dimensional characteristics of an organism it is possible to
      consider (count) fixed somatotipic of feature as morphological markers of
      predisposition to scoliotic deformation.

PMID- 11452433
TI  - [Somatotype and the human body development during first childhood].
AB  - Change of somatotype anthropometric characteristics, formation and rate of growth
      were followed up in longitudinal study in children aged 3-7, 138 girls and 150
      boys aged 3 and 54 boys and 46 girls aged 7 were studied. Somatotypes were
      evaluated by means of statistics. It was established that within the observation
      period somatotype differences in children intensify due to different rate of
      constitutionally significant body sizes. In nearly half of the children
      somatotypes change due to growth or reduction of signs determining them.

PMID- 11452434
TI  - [Monoclonal antibodies to the nuclear protein PCNA for detection of proliferating
      cells in the developing brain of a human embryo].

PMID- 11452435
TI  - [Initial stages of differentiation of pyramidal neurons in deep layers of the
      mouse neocortex in the prenatal period].
AB  - The time of initiation of neuron differentiation in deep neocortical layers was
      determined in mouse embryos and total effect of ionizing radiation on the
      developing mouse brain was evaluated. The population of cells that form layers V
      and VI with differentiation occurring in a half of them was shown to be present
      in mice embryos on d13. This population comprises both non differentiated
      neuroblasts and juvenile neurons of certain level of differentiation. They make
      the half of total population and their number remains unchanged on d14.
      Irradiation of mouse embryos at early postimplantation stage (d12) causes severe
      disturbances of neocortex development that are conditioned by massive cell death,
      abnormal development of all the brain structures and reduction of brain volume.
      Irradiation of mice embryos on d 13 and 14 induces massive death of migrating and
      mitotic cells in populations responsible for forming deep cortical layers. By the
      end of prenatal period either lack or insufficient development of layers V and VI
      was observed manifested in significant decline of cell number, spacing out and
      loss of neurons in certain regions. In embryos irradiated within these terms
      upper layers of cortex may form, although density of cell distribution in them is
      lower than in control.

PMID- 11452436
TI  - [Current concepts of structural and functional organization of interneuronal
      synapses in the central nervous system].

PMID- 11452437
TI  - [Teaching histology, cytology, and embryology to students of the Department of
      Sports Medicine].

PMID- 11452440
TI  - [Regulation of cell cycle checkpoints in mammalian cells].

PMID- 11452441
TI  - [Intracellular protein sorting--regulation by AP complexes].

PMID- 11452442
TI  - [Dynamic conformational changes which support the function of molecular chaperone
      GroE].

PMID- 11452443
TI  - [Function of membrane phospholipid dynamics in eukaryotic cells].

PMID- 11452444
TI  - [Signal transduction for differentiation of human hematopoietic myeloid cell].

PMID- 11452445
TI  - [Physiological functions of DNA topoisomerase II beta].

PMID- 11452446
TI  - [Regulation of stress-dependent signal transduction by protein phosphatase 2C].

PMID- 11452447
TI  - [The adhesion mechanism of lactic acid bacteria bound to intestine through sugar
      chain].

PMID- 11452448
TI  - [Progress in research on red cell membrane disorders: from the genome to the
      postgenome era].

PMID- 11452449
TI  - [Novel diagnostic procedures for hematologic malignancies on the basis of genomic
      alterations].

PMID- 11452450
TI  - [Target molecules of anti-tumor drugs and cell checkpoints].

PMID- 11452451
TI  - [Anti-tumor immunotherapy for acute leukemia using dendritic cells].

PMID- 11452452
TI  - [Prognostic factors and treatment of acute myelogenous leukemia based on clinical
      results obtained by the Japan Adult Leukemia Study Group].

PMID- 11452453
TI  - [Chemotherapy for refractory acute leukemia].

PMID- 11452454
TI  - [ATRA therapy for adult T-cell leukemia].

PMID- 11452455
TI  - [Indications for allogeneic bone marrow transplantation (BMT) in adult acute
      myelogenous leukemia: matched-pair analysis in comparison with chemotherapy in
      patients achieving initial remission].

PMID- 11452456
TI  - [Molecular pathogenesis of Fanconi anemia: from genes to phenotypes].

PMID- 11452457
TI  - [DNA methylation in the promoter regions of the human red cell membrane protein
      genes].

PMID- 11452458
TI  - [Erythropoiesis and signal transduction: basic and clinical aspects].

PMID- 11452459
TI  - [Disorders of iron metabolism involving erythropoiesis: molecular mechanism of
      gut-liver-bone marrow axis].

PMID- 11452460
TI  - [Mutation of H-ferritin gene in a family associated with hereditary iron
      overload: a new iron overload-related gene?].

PMID- 11452461
TI  - [Follicular lymphoma in two brothers].
AB  - Two brothers, whose parents had a history of exposure to atomic bomb radiation,
      developed non-Hodgkin's lymphoma. The younger brother, a 48-year-old man, was
      diagnosed as having follicular small-cleaved cell lymphoma in October, 1996. He
      had extranodal lymphoma involvement of the right kidney, bone marrow and skin, in
      addition to generalized lymphadenopathy. He was treated with intermittent COP
      chemotherapy, and good control of the lymphoma was obtained. The elder brother,
      aged 50 years, was diagnosed as having follicular mixed cell lymphoma in May,
      1998. He also had extranodal lymphoma involvement of the right parotid gland and
      bone marrow, as well as generalized lymphadenopathy. After one course of CHOP
      chemotherapy, he developed paresis of the lower legs and was found to have a mass
      at the Th5-6 vertebrae by CT scan. After four courses of CHOP chemotherapy
      followed by ESHAP chemotherapy and radiotherapy, he achieved complete remission,
      and has since been well. Follicular lymphoma occurring among siblings is rare.
      Further cytogenetic and molecular studies may provide a better understanding of
      its etiology.

PMID- 11452462
TI  - [Hemophagocytic syndrome with hemophagocytes in the peripheral blood].
AB  - A 79-year-old man developed a high fever, facial erythema, anemia and
      thrombocytopenia during conservative therapy for ischemic colitis. Peripheral
      hemophagocytes (PHP) were identified in smear specimens of peripheral blood, and
      hemophagocytes also showed proliferation in the bone marrow. After treatment with
      steroid and antibiotics under a diagnosis of bacteria-associated hemophagocytic
      syndrome, the patient recovered rapidly. Although the prognosis of hemophagocytic
      syndrome (HPS) depends on the underlying disease, any delay in diagnosis can
      sometimes result in a poor outcome in cases of infection-associated
      hemophagocytic syndrome. In the present case, early diagnosis of bacteria
      associated hemophagocytic syndrome was made by detection of PHP. The appearance
      of PHP in virus-associated hemophagocytic syndrome (VAHS) and after
      administration of macrophage colony stimulating factor has been described.
      However, the significance and cytological characteristics of PHP have been
      unknown. In this report, we propose that PHP can be a useful indicator for early
      diagnosis of HPS, and we report 7 additional cases in which the PHP was detected
      retrospectively. The cytological characteristics and biological significance of
      PHP are discussed.

PMID- 11452463
TI  - [CD56- and CD4-positive non-Hodgkin's lymphoma of probable T-cell origin].
AB  - A 65-year-old man was admitted with swelling of the right neck and bilateral
      inguinal lymph nodes. Endoscopic examination revealed no nasal infiltration.
      Pathological examination of a neck lymph node biopsy specimen revealed peripheral
      T-cell lymphoma according to the Revised European-American Classification of
      Lymphoid Neoplasms (REAL). The phenotype of the lymphoma cells was CD56+, CD16-,
      CD2+, surface CD3-, cytoplasmic CD3+, CD4+, CD8-, CD5+, CD7- and CD45RO+. May
      Giemsa staining demonstrated no azurophilic granules in the lymphoma cells.
      Immunohistopathologic examination showed negativity for TIA-1 and granzyme B, and
      rearrangement of the TCR C beta 1 gene was also noted. These findings strongly
      suggested that this was a T-cell lymphoma. The patient received 8 courses of CHOP
      chemotherapy plus sobuzoxane. This led to a marked decrease of lymph node
      swelling, and currently the patient is still in remission. According to the REAL
      classification, T/NK-cell lymphomas are included among the peripheral T cell
      tumours, and seem to constitute a heterogeneous group of neoplasms. Although some
      cases of CD4+ CD56+ lymphoma have been reported, the present case appears to be
      the first example to show TCR gene rearrangement and negativity for TIA-1 and
      granzyme B. Since the classification of T/NK-cell lymphoma is still
      controversial, accumulation of such cases may help to better define T/NK-cell
      neoplasms.

PMID- 11452464
TI  - [European-American-type hairy cell leukemia without splenomegaly, treated
      successfully with deoxycoformycin].
AB  - A 55-year-old Japanese man was hospitalized on October 5, 1999, because of high
      fever. Physical examination revealed neither lymphadenopathy nor hepato
      splenomegaly. Laboratory data on admission showed a white blood cell count of
      1,580/microliter, a hemoglobin level of 9.1 g/dl, and a platelet count of 113 x
      10(3)/microliter. A small percentage of abnormal mononuclear cells were present
      in the peripheral blood. A bone marrow biopsy specimen demonstrated myelofibrosis
      and diffuse infiltration of abnormal monoculear cells with a mature B cell
      phenotype. A bone marrow aspirate showed 29% abnormal mononuclear cells, which
      had an indented or folded nucleus and reticular nuclear chromatin. Moderate to
      strong tartarate-resistant acid phosphatase activity was detected in these cells.
      Although the cytoplasmic projections were poorly preserved in specimens stained
      with May-Giemsa, fresh preparations showed numerous slender cytoplasmic
      projections by phase-contrast microscopy. The hairy cells had the phenotype CD5-,
      CD10-, CD11c+, CD19+, CD20+, CD25+, lambda. The patient was diagnosed as having
      European-American-type hairy cell leukemia (HCL) without splenomegaly, which is
      quite rare in Japan. The value of phase-contrast microscopy for recognition of
      the hairy cells was emphasized. The patient was treated successfully with
      deoxycoformycin (DCF).

PMID- 11452466
TI  - [The intubating laryngeal mask: its advantages and limitations].
AB  - It has been hypothesized that the intubating laryngeal mask (ILM) has some
      advantages: (1) tracheal intubation is achieved with a neutral head-neck position
      and limited mouth opening, (2) intubation is not interfered with blood and
      secretion in the mouth, (3) ventilation via the device is possible, and (4) it is
      easy to use. Many studies have brought evidences for these points. Actually,
      cervical spine movement is unavoidable to a small extent although tracheal
      intubation is possible with a neutral head-neck position. Degree of hemodynamic
      changes and incidences of postoperative airway complications are similar between
      the ILM and the laryngoscope. ILM-users should pay attention to these limitations
      when they use the ILM.

PMID- 11452467
TI  - [The memory of tracheal extubation during emergence from general anesthesia].
AB  - The authors evaluated the memory of tracheal extubation during emergence from
      general anesthesia. We screened 3,039 consecutive patients undergoing elective
      surgery from November 1, 1998 to December 31, 1999. Of 3,039 patients, 1,993 were
      interviewed postoperatively at the anesthesia clinic and 202 had the memory of
      tracheal extubation. The incidence was higher in the groups of female, younger
      and propofol anesthesia compared to male, elder and inhalational anesthesia,
      respectively. The patients who were dissatisfied with anesthesia were more in the
      patients with the memory of tracheal extubation compared to the patients without
      the memory. We consider that the memory of tracheal extubation contributes to the
      dissatisfaction with anesthesia.

PMID- 11452468
TI  - [Depressive effect of dibucaine and bupivacaine on the growth of axons from
      cultured neuron of Lymnaea stagnalis].
AB  - The depressive effect of dibucaine (n = 8) was compared with that of bupivacaine
      (n = 9) using identified cultured neurons (A cluster) of Lymnaea stagnalis.
      Cultured interneurons exhibit extensive neurite outgrowth within 14-20 hours when
      placed in brain conditioned media. The changes of cultured neuron were recorded
      using a color video camera directly connected to an inverted microscope and the
      images were stored on digital video tape. Local anesthetics were added to the
      culture dish, with final concentrations of 1 x 10(-6) M-8 x 10(-4) M of dibucaine
      and 1 x 10(-5) M-8 X 10(-3) M of bupivacaine. We examined the damage of growth
      cone before and 30 minute after local anesthetics administration. Histologic
      damage were scored from moderate to severe compared to the control before
      dibucaine or bupivacaine administration. Dibucaine or bupivacaine damaged the
      growth cone moderately in the concentration of 1 x 10(-5) M or 4 x 10(-4) M,
      respectively. While dibucaine or bupivacaine damaged it severely in the
      concentration of 8 x 10(-5) M or 2 x 10(-3) M, respectively. These results
      suggest that bupivacaine is safer than dibucaine with the concentration we use in
      clinical practice.

PMID- 11452469
TI  - [Cuff failure in tracheal tubes sprayed with lidocaine].
AB  - Lidocaine jelly or spray is usually applied to tracheal tube cuffs as lubricants,
      and we encountered some cuff troubles in using the spray. Damages on polyvinyl
      chloride (PVC) tracheal tube cuffs by applying lidocaine spray have been
      reported. We studied cuff injury with 5 kinds of tracheal tubes (PVC and non-PVC
      cuffs) with three different substances (normal saline, lidocaine jelly and
      lidocaine spray). No tracheal tube cuffs were damaged by normal saline and
      lidocaine jelly, while lidocaine spray changed the shape of some tracheal tube
      cuffs (PVC and non-PVC). Therefore, we recommend to apply lidocaine jelly on tube
      cuffs rather than lidocaine spray, even on non-PVC cuffs.

PMID- 11452470
TI  - [Whole body heat production as a quantitative marker of anesthetic management
      under general anesthesia].
AB  - In order to evaluate the effects of the rapid induction and the slow induction of
      general anesthesia on the management of anesthesia and the circadian rhythm, the
      time-dependent whole body heat production in mice (ICR, male, 6 to 10 weeks after
      birth) was measured by calorimeter. In the single administration of either an
      i.v. anesthetic (thiamylal) or a volatile anesthetic (isoflurane), the minimum
      heat production and its duration time were similar. In the co-administration of
      i.v. and volatile anesthetics, the minimum heat production was significantly
      lower (P < 0.01) and the duration of this minimum production was significantly
      more sustained (P < 0.01) compared to those seen in the single administration of
      each anesthetic. Moreover, by measurement of the whole body heat production, the
      slow induction of general anesthesia markedly affected the circadian rhythm on
      the next postoperative day. These results indicate that the measurement of the
      whole body heat production will be a marker for the recovery from general
      anesthesia and the return to the usual life style (such as the QOL).

PMID- 11452471
TI  - [A case of coring on using a 1% Diprivan vial].
AB  - We report a case in which two fragments due to coring from the rubbercap of a 50
      ml Diprivan vial were detected only immediately before infusion to a patient. The
      attending anesthesiologist noticed the foreign bodies by chance. The rubbercap
      was punctured only once, but the two foreign bodies from the syringe were proved
      to be from the rubbercap by infrared spectrometer analysis. It is difficult to
      recognize the small fragments in Diprivan which is white unclear emulsion.
      Therefore, anesthesiologists should be aware of the danger of coring.

PMID- 11452472
TI  - [Anesthesia using propofol for a patient with arthrogryposis multiplex
      congenita].
AB  - Arthrogryposis multiplex congenita (AMC) is a syndrome with multiple persistent
      limb contractures, often accompanied by associated anomalies. Pediatric patients
      with AMC frequently require operations, necessitating general endotracheal
      anesthesia. We report on the anesthesia used for a 14-year-old male with AMC, who
      required the surgical removal of soft tissue from both hip joints. We used
      propofol and vecuronium bromide to induce anesthesia, and maintained anesthesia
      with 40% nitrous oxide, oxygen, and propofol at 6 mg.kg-1.1 hr-1. Both induction
      and maintenance were smooth, and no hyperthermia occurred perioperatively.
      Propofol can be safely used for anesthesia in AMC patients.

PMID- 11452473
TI  - [Anesthetic management of a patient with a giant bulla and liver cirrhosis using
      a laryngeal mask airway and epidural analgesia].
AB  - A laryngeal mask airway (LMA) and epidural analgesia were used for anesthetic
      management of microwave coagulo-necrotic therapy for multiple hepatoma in a 76
      year-old male with a giant bulla and liver cirrhosis. Since bleeding times, PT
      and APTT were within normal limits, an epidural catheter was inserted between Th9
      and 10 interspaces in operating room. After preoxygenation, general anesthesia
      was induced with propofol 120 mg. After insertion of a LMA, anesthesia was
      maintained under spontaneous breathing with sevoflurane (1-1.5%) in about 45%
      oxygen and nitrogen. During the operation, 2% lidocaine was injected continuously
      into the epidural space. Continuous epidural injection of 2% lidocaine was found
      to be very effective for obtaining abdominal muscle relaxation and perioperative
      pain management. Postoperative chest X ray did not show any signs of rupture of
      the giant bulla, and any neurological abnormalities due to the epidural hematoma
      were not encountered. We could reduce the risk of rupture of a giant bulla during
      general anesthesia using a LMA and epidural analgesia.

PMID- 11452474
TI  - [Intracerebral hemorrhage induced by cerebral amyloid angiopathy in a patient
      during transurethral electrocoagulation].
AB  - A 68-year-old female with severe anemia due to a bleeding bladder was scheduled
      for emergency transurethral electrocoagulation surgery under general anesthesia.
      Her preoperative consciousness was clear. After preoxygenation, general
      anesthesia was induced with ketamine 40 mg and vecuronium 6 mg. After tracheal
      intubation, anesthesia was maintained with nitrous oxide, oxygen, and isoflurane
      (0.5-0.8%). During the operation, a large fluctuation in blood pressure was
      observed. The operation was completed uneventfully, but the patient did not
      recover smoothly from the anesthesia. A few minutes later, signs of neurological
      abnormality were observed, and an emergency brain CT scan was performed. Since CT
      images of the brain showed extensive intracerebral hemorrhage (ICH) and edema,
      emergency craniotomy was performed. Postoperative pathological examination showed
      that the cause of the ICH was cerebral amyloid angiopathy (CAA). Since the
      incidence of CAA is relatively high in elderly people and CAA can cause ICH due
      to fluctuation in blood pressure, prudent anesthetic management is needed for
      elderly patients undergoing emergency operations, particularly an operation
      leading to a decrease in blood volume.

PMID- 11452475
TI  - [Anesthetic management of a child with Klippel-Feil syndrome associated with
      severe scoliosis].
AB  - We experienced an anesthetic management of a female child with Klippel-Feil
      syndrome complicated with severe scoliosis. This patient showed airway problems
      in anesthetic management because of limited neck movement due to fused cervical
      supine and winding airway due to scoliosis. A laryngeal mask (LM) was useful for
      ventilation but we fitted LM carefully because of her orolaryngeal anomaly.
      Intubation was very difficult through LM because the axis of LM was not on the
      laryngeal axis and the tip of the tracheal tube caught the epiglottis and
      arytenoid cartilage.

PMID- 11452476
TI  - [Anesthetic management of a patient with congenital antithrombin III Deficiency
      using temporal inferior vena cava filter].
AB  - We described the perioperative management of a patient with congenital
      antithrombin III deficiency using temporal inferior vena cava filter. A 30-year
      old man with congenital antithrombin III deficiency was scheduled for artificial
      head replacement of the hip joint under general anesthesia. He was diagnosed as
      having congenital antithrombin III deficiency when he had had an episode of
      venous thrombosis after artificial head replacement of the right hip joint. He
      had been taking warfarin as an anticoagulant, and it was discontinued three days
      before surgery. To prevent perioperative thrombus formation, the plasma AT III
      activity was maintained above 80% before, during and after surgery using AT III
      concentrates. We also placed the temporal inferior vena cava filter. There was no
      serious thrombosis or embolism perioperatively. The use of the filter during the
      perioperative period helped to avoid development of serious thrombosis and
      embolism.

PMID- 11452477
TI  - [Unilateral pulmonary fibrosis following ipsilateral single-lung ventilation and
      anesthesia].
AB  - We experienced a rare case of unilateral pulmonary fibrosis following ipsilateral
      single-lung ventilation and anesthesia. A 75-year-old man with a 1-pack a day
      smoking history for 50 years was scheduled for right upper and middle lobectomy
      for lung cancer. The trachea and left bronchus were intubated with a 37-Fr double
      lumen endobronchial tube, and anesthesia was maintained with oxygen, nitrous
      oxide, isoflurane, and epidural lidocaine. Left single-lung ventilation was
      maintained for 3.5 hours with FIO2 at 0.8-1.0, vital capacity at 10 ml.kg-1, and
      peak inspiratory pressure at 25 cmH2O. On postoperative day 55, reticular nodular
      density in chest roentogenography appeared only in the left lung while right lung
      showed pleural fluid and pneumonia. On postoperative day 105, a high-resolution
      computed tomographic scan revealed honeycomb pattern in the left lung and
      organized pneumonia in the right lung. The patient died from respiratory failure
      on postoperative day 155, and autopsy was not performed. Although the causative
      mechanisms of unilateral pulmonary fibrosis in this case was unclear, the patient
      had not been exposed to any drugs and inhalation agents known to induce pulmonary
      fibrosis. We speculate that high oxygen concentration, high peak inspiratory
      pressure, and overdistension of the left lung during the left single-lung
      ventilation and anesthesia were likely major initiating and contributing factors.

PMID- 11452478
TI  - [Perioperative management using propofol in a patient with uncontrolled
      preoperative hyperthyroidism].
AB  - There is a risk of thyrotoxic crisis during and after surgery in patients with
      uncontrolled hyperthyroidism. To avoid this, suppression of sympathetic activity
      during the perioperative period is important. For this purpose, we used propofol
      for the anesthetic and the postoperative management in a 19-year-old female with
      uncontrolled hyperthyroidism. Propofol 6 to 8 mg.kg-1.hr-1 plus 66% of nitrous
      oxide was not sufficient to obtain hemodynamic stability during the surgery, but
      propofol 3 mg.kg-1.hr-1 produced optimal sedation in the postoperative period.
      The results demonstrate that propofol is useful for the anesthetic management of
      patients with uncontrolled hyperthyroidism.

PMID- 11452479
TI  - [Usefulness of epidural infusion of ketamine for relief of localized superficial
      pain].
AB  - Three patients with localized superficial pain had their pain alleviated by
      single epidural infusion with low dose ketamine. The patients are as follows: a
      62-year-old female with herpetic neuralgia on her right sixth thoracic nerve
      area; a 52-year-old male whose left shoulder, anterior chest and abdomen had been
      burned by acetylene gas; and a 49-year-old male whose bilateral hands suffering
      from frostbite by propane gas. Epidural tube insertion to administer a single
      dose of 10 mg ketamine with lidocaine or bupibacaine was performed in all the
      three patients. They were administered single epidural infusion of 10 mg ketamine
      with lidocaine or bupibacaine everyday and they continued to receive epidural
      block with lidocaine or bupivacaine including buprenorphine or morphine.
      Therefore, we suspect that single epidural infusion of ketamine, an antagonist
      for N-methyl-D-aspartic acid receptor, could be an effective and useful
      alternative treatment in patients with various refractory localized superficial
      pain of either acute or chronic nature.

PMID- 11452480
TI  - [Anesthetic management for gastrojejunostomy in a patient with hemiplegia and
      recurrent laryngeal nerve palsy].
AB  - A 70-year-old man who had undergone a low anterior resection for primary rectal
      cancer 9 years before complained of anorexia, hemiplegia, and recurrent laryngeal
      nerve palsy. The anorexia was caused by duodenal stenosis due to swollen lymph
      nodes, the hemiplegia was caused by a metastatic brain tumor, and the recurrent
      laryngeal nerve palsy was caused by metastases of the cancer to the mediastinal
      space. Metastases were also found in the bilateral lungs, liver, ureter, and
      cervical vertebra. In choosing the anesthesia for the gastrojejunostomy to
      improve the malnutrition of this patient, we decided, on the basis of the
      patient's full stomach, malnutrition, hypovolemia, hemiplegia, cerebral
      compression, recurrent laryngeal nerve palsy, renal dysfunction, and respiratory
      dysfunction, to use thoracic epidural anesthesia rather than spinal anesthesia or
      general anesthesia. Thoracic epidural anesthesia could provide sufficient
      analgesia, and the operation was uneventful. In anesthetic management of an end
      stage patient undergoing a palliative operation like this, we should consider the
      purpose of the operation, its complications, and further complications which may
      be induced by anesthesia in order to plan out an anesthetic regimen unlikely to
      lead to harmful events in perioperative period.

PMID- 11452481
TI  - [Education of basic/advanced life support and emergency medicine for
      anesthesiologists: a survey of chairpersons at university department and newly
      board certified anesthesiologists].
AB  - To determine how the education of basic life support (BLS)/advanced cardiac life
      support (ACLS) and emergency medicine for anesthesiologists is conducted, we
      performed a survey of chairpersons at university departments and newly board
      certified anesthesiologists in 1999. Basic and advanced life support courses for
      residents were provided in more than half of the anesthesiology departments that
      responded to this survey. However, approximately only 10% of the respondents had
      regular BLS/ACLS courses for residents. On the other hand, more than 80% of
      respondents considered a rotation in emergency medicine desirable as a part of
      anesthesia training. To improve the resuscitation skills of anesthesiologists, an
      urgent need to establish regular BLS/ALS courses and educational programs in
      emergency medicine in anesthesia training does exist.

PMID- 11452482
TI  - [The effectiveness of ozonated water for hand washing before surgery].
AB  - Using an ozonated water-dispensing machine for sterilization of hands (Mediaqua
      MA-III; Core Medical Co., Ltd, Tokyo, Japan), we investigated the effectiveness
      of ozonated water as a disinfectant for hand washing before surgery. The
      effectiveness of this new hand-washing method, using 4 ppm of ozonated water,
      which is expected to have a short-term bactericidal effect, and 0.2% benzalkonium
      chloride/83% ethanol solution (Welpas), which is expected to have a long-term
      bactericidal effect, was compared with that of the conventional hand-washing
      method (Furbringer's method using a scrubbing agent containing povidone-iodine).
      The results showed no significant differences in the numbers of live bacteria and
      exponential reduction rates in live bacteria. Thus, this new method for hand
      washing using ozonated water is an effective method for sterilization of the
      hands before surgery.

PMID- 11452483
TI  - [Perioperative mortality and morbidity for the year of 1999 in 466 Japanese
      Certified Anesthesia-training Hospitals: with special reference to ASA-physical
      status--report of Committee on Operating Room Safety of Japan Society of
      Anesthesiologists].
AB  - Perioperative mortality and morbidity in Japan for the year 1999 were studied
      retrospectively. Committee on Operating Room Safety of the Japan Society of
      Anesthesiologists (JSA) sent confidential questionnaires to 774 Certified
      Training Hospitals of JSA and received answers from 60.2% of the hospitals. We
      analyzed their answers with special reference to ASA physical status (ASA-PS).
      The total number of anesthetics analyzed was 655, 644. Mortality and morbidity
      due to all kinds of causes including anesthetic management, intraoperative
      events, co-existing diseases, and operation were as follows. The incidence of
      cardiac arrest (per 10,000 anesthetics) was 0.68, 3.76, 14.37, 67.03, 0.36, 4.68,
      27.96, 206.30 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV
      E, respectively. The incidences of critical events including cardiac arrest,
      severe hypotension, and severe hypoxemia were 8.93, 26.99, 71.30, 188.52, 8.68,
      31.27, 136.16, and 790.92 in patients with ASA-PS of I, II, III, IV, I E, II E,
      III E, and IV E, respectively. The mortality rates (death during anesthesia and
      within 7th postoperative day) after cardiac arrest were 0.16, 0.94, 5.71, 33.51,
      0.00, 1.46, 16.41 and 167.76 per 10,000 anesthetics in patients with ASA-PS of I,
      II, III, IV, I E, II E, III E, and IV E, respectively. The overall mortality
      rates were 0.24, 1.66, 12.16, 67.03, 0.00, 3.51, 34.65 and 417.14 in patients
      with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. Overall
      mortality and morbidity were higher in emergency anesthetics than in elective
      anesthetics. ASA-PS correlated well with overall mortality and with morbidity,
      regardless of etiology. The incidences of cardiac arrest totally attributable to
      anesthesia were 0.24, 0.45, 1.47, 8.38, 0.36, 1.75, 2.43 and 11.34 in patients
      with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The
      incidences of all critical events totally attributable to anesthesia were 4.92,
      8.81, 14.74, 20.95, 4.34, 11.40, 15.80 and 22.67 in patients with ASA-PS of I,
      II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates after
      cardiac arrest totally attributable to anesthesia were 0.00, 0.00, 0.61 and 4.53
      in patients with ASA-PS of I-IV, I E-II E, III E, and IV E, respectively. The
      overall mortality rates totally attributable to anesthesia were 0.00, 0.04, 0.18,
      0.00, 0.00, 0.61 and 4.53 in patients classified to ASA-PS of I, II, III, IV, I E
      II E, III E, and IV E, respectively. Only one death, due to overdose of
      anesthetics, was reported among patients with good physical status (ASA-PS of I,
      II, II E and II E). Anesthetic management was mainly responsible for critical
      events in patients with good physical status, while co-existing diseases were in
      those with poor physical status. The major co-existing diseases or conditions
      leading to critical events were heart diseases in elective anesthetics, and
      hemorrhagic shock in emergency anesthetics. We reconfirmed that ASA-PS is
      beneficial to predict perioperative mortality and morbidity. It also seems likely
      that we should make much more efforts to reduce anesthetic morbidity in patients
      with good physical status, and to improve preanesthetic assessment and
      preparation of cardiovascular conditions in those with poor physical status.

PMID- 11452484
TI  - [Usefulness of 99mTc-GSA scintigraphy for estimation of residual hepatic
      functions and postoperative changes of HH15 and LHL15].
AB  - We investigated the usefulness of 99mTc-GSA scintigraphy for estimation of
      residual hepatic functions and postoperative changes of HH15 and LHL15. 99mTc-GSA
      scintigraphy was performed on 61 patients and following points were studied: 1)
      correlation between HH15-LHL15 and conventional liver function tests, 2)
      correlation between HH15-LHL15 and the Child classification, 3) relations of
      preoperative HH15 and LHL15 to postoperative complications after hepatectomy, 4)
      early changes of HH15 and LHL15 after hepatectomy, 5) changes of HH15 and LHL15 1
      year after hepatectomy, and 6) changes of HH15 and LHL15 1 year after Hassab's
      operation. Results were as follows. 1) There were significant relations between
      preoperative HH15 and ICGR15 and Alb. There were significant relations between
      preoperative LHL15 and ICGR15, T-Bil, Alb, HPT and ChE. 2) There were significant
      relations between preoperative HH15-LHL15 and the Child classification. 3) In Hr2
      group, preoperative LHL15 of patients who contracted postoperative complications
      had been significantly lower than that of those who did not. 4) There were no
      early changes of HH15 and LHL15 after hepatectomy. 5) HH15 and LHL15 were
      significantly improved 1 year after hepatectomy. 6) HH15 were significantly
      improved 1 year after Hassab's operation. We concluded that 99mTc-GSA
      scintigraphy is useful for estimation of residual liver function tests and for
      investigation of changes after surgery from viewpoints different from
      conventional hepatic function tests.

PMID- 11452485
TI  - [Quantitative estimation of brain atrophy and function with PET and MRI two
      dimensional projection images].
AB  - PURPOSE: The purpose of this paper is to estimate the extent of atrophy and the
      decline in brain function objectively and quantitatively. METHODS: Two
      dimensional (2D) projection images of three-dimensional (3D) transaxial images of
      positron emission tomography (PET) and magnetic resonance imaging (MRI) were made
      by means of the Mollweide method which keeps the area of the brain surface. A
      correlation image was generated between 2D projection images of MRI and cerebral
      blood flow (CBF) or 18F-fluorodeoxyglucose (FDG) PET images and the sulcus was
      extracted from the correlation image clustered by K-means method. Furthermore,
      the extent of atrophy was evaluated from the extracted sulcus on 2D-projection
      MRI and the cerebral cortical function such as blood flow or glucose metabolic
      rate was assessed in the cortex excluding sulcus on 2D-projection PET image, and
      then the relationship between the cerebral atrophy and function was evaluated.
      This method was applied to the two groups, the young and the aged normal
      subjects, and the relationship between the age and the rate of atrophy or the
      cerebral blood flow was investigated. This method was also applied to FDG-PET and
      MRI studies in the normal controls and in patients with corticobasal
      degeneration. RESULTS: The mean rate of atrophy in the aged group was found to be
      higher than that in the young. The mean value and the variance of the cerebral
      blood flow for the young are greater than those of the aged. The sulci were
      similarly extracted using either CBF or FDG PET images. CONCLUSIONS: The purposed
      method using 2-D projection images of MRI and PET is clinically useful for
      quantitative assessment of atrophic change and functional disorder of cerebral
      cortex.

PMID- 11452486
TI  - [Development of the chromatography analysis of liquid trapping 99mTc-Technegas
      using Jikei impinger].
AB  - We developed the equipment which collected 99mTc-Technegas into liquid (saline)
      and named this equipment an impinger of Jikei University Style. We further
      developed a technique using this impinger to evaluate its formation qualitatively
      by paper chromatography. Utilizing this technique we investigated various factors
      that caused environmental contamination by 99mTc-Technegas, including changes
      over time in a Technegas generator. It was demonstrated that upon getting mixed
      with oxygen gas to the argon gas, the Technegas generator induced contamination
      of 99mTc-Pertechnegas easily, leading to changes in its formation. The change of
      formation quality of the Technegas generator with the lapse of time was also
      revealed. These findings indicated that the maintenance and inspection of the
      equipment were important. This method is a simple and easy technique for the
      evaluation of 99mTc-Technegas formation, making it possible to perform the
      quality control of examination agent and the Technegas generator.

PMID- 11452487
TI  - [Gastrointestinal bleeding from capillary hemangioma of the ileum detected by
      99mTc-HSAD scintigraphy].
AB  - It has been well-known that technetium-99m-human serum albumin
      diethylenetriaminepenta-acetic acid (99mTc-HSAD) scintigraphy is useful for
      diagnosis of the localization of the gastrointestinal arterial or venous
      bleeding. In this report, we describe a case of venous bleeding from capillary
      hemangioma of the ileum end detected by 99mTc-HSAD scintigraphy. This patient was
      a 9-year-old girl with severe anemia. Gastrointestinal bleeding was suspected
      from her clinical course and laboratory tests. Immediately after melena occurred,
      99mTc-HSAD scintigraphy showed the extravasation of RI suggesting
      gastrointestinal bleeding in the ileum end. Abdominal angiography immediately
      after 99mTc-HSAD scintigraphy, however, could not show the extravasation of
      contrast agent. Because the condition of the patient became worse, laparotomy was
      performed on the basis of 99mTc-HSAD scintigraphy findings. At surgery, venous
      bleeding from capillary hemangioma in the ileum end was observed. It was
      suggested that 99mTc-HSAD scintigraphy was very useful for identifying the
      gastrointestinal venous bleeding.

PMID- 11452488
TI  - [Usefulness of gallium-67 scintigraphy in diagnosing pyothorax-associated
      lymphoma].
AB  - Two cases of pyothorax-associated malignant lymphoma were reported. The presence
      of chronic tuberculous pyothorax after thoracoplasty and the development of non
      Hodgkin's lymphoma on the chest wall are closely related. Both patients had
      suffered from tuberculous pyothorax for more than thirty years, and developed new
      painful chest wall tumors. CT and MRI delineated both malignant lymphoma and
      pyothorax. Gallium-67 accumulated strongly in malignant lymphoma, however did not
      in pyothorax. Gallium-67 scintigraphy was useful for detection of malignant
      lymphoma in both cases; therefore it could be a useful test for diagnosing of
      pyothorax-associated lymphoma.

PMID- 11452489
TI  - [Aneurysm-like wall motion abnormality in hibernating myocardium detected by
      stress thallium scintigraphy].
AB  - A 70-year-old female patient presented and ECG with QS patterns and ST elevation
      in V1-3. Left ventriculography showed severely abnormal wall motion of the
      anteroseptal similar to a left ventricular aneurysm. Based on previous experience
      that 201Tl myocardial scintigraphy revealed possible myocardial viability in a
      patient with left ventricular aneurysm suspected of having apparently no
      myocardial viability, percutaneous transluminal coronary angioplasty (PTCA) was
      performed for severe stenosis of the left anterior descending artery. Follow-up
      images 3 months later showed a remarkable improvement in parietal motility of the
      left ventricle and recovery of almost normal cardiac function. This case
      demonstrates that exercise myocardial scintigraphy is useful for diagnosing
      hibernating myocardium associated with severely abnormal parietal motility, such
      as left ventricular aneurysm.

PMID- 11452490
TI  - [Disseminated bone marrow metastases from gastric cancer: detection and
      monitoring the effectiveness of chemotherapy by bone marrow scintigraphy].
AB  - Disseminated bone marrow metastasis of cancer is a critical condition, frequently
      complicated by disseminated intravascular coagulation (DIC). A 32-year-old man
      with gastric cancer was diagnosed as having disseminated bone marrow metastases.
      Bone scintigraphy demonstrated many abnormal radionuclide accumulations in the
      whole body. Bone marrow aspiration revealed cancer cells. Bone marrow
      scintigraphy with 111In-Cl3 demonstrated central marrow failure and peripheral
      expansion. The remission of DIC was observed after sequential methotrexate and 5
      FU therapy, then uptake of radionuclide in the central bone marrow was remarkably
      improved by bone marrow scan. After thirteen anti-cancer chemotherapies,
      recurrence of DIC was suspected because of the reduction of blood platelet count.
      Nevertheless, repeated bone marrow scan still demonstrated the central bone
      marrow clearly. The patient discharged from our hospital without the recurrence
      of DIC. We considered bone marrow scintigraphy is useful in the detection of
      disseminated bone marrow metastases of cancer and monitoring the effectiveness of
      chemotherapy.

PMID- 11452491
TI  - [Clinical evaluation of "Takotsubo" cardiomyopathy with 123I-MIBG myocardial
      scintigraphy: a case report].
AB  - We report a case of "Takotsubo" cardiomyopathy that was considered to be caused
      by hypercatecholaminemia due to mental stress. Myocardial scintigraphy using 123I
      MIBG revealed severe damage to the myocardial sympathetic nerve terminals at the
      site of reduced left ventricular wall motion on left ventriculography. In this
      case, cardiac nuclear imaging with 123I-MIBG appeared to be useful for
      understanding the pathophysiology when combined with ECG and left
      ventriculography.

PMID- 11452492
TI  - [Assessment of left ventricular function with the solid-state digirad 2020tc
      Imager].
AB  - Multigated equilibrium radionuclide ventriculography from best septal position
      (LAO view) was performed in 17 patients with cardiac disease with a single
      detector Anger-type gamma camera (GCA 602A, Toshiba), then immediately imaged
      with a solid-state, multi-crystal gamma camera (Digirad 2020tc Imager).
      Acquisition times were the same of 10 minutes. The solid-state gamma camera uses
      CsI(Tl) as the scintillation material and a Si photodiode. CsI(Tl) has a higher
      density and higher atomic number than NaI(Tl), so that its efficiency for
      detecting gamma rays is higher. To confirm this, total acquisition counts in 17
      patients obtained from the 2020tc Imager were significantly higher than those
      obtained from the Anger-type camera (7847 +/- 2061 K vs. 4427 +/- 1162 K counts,
      p < 0.0001). In comparing left ventricular ejection fractions obtained from the
      Anger-type camera and the 2020tc Imager data, an excellent correlation was
      revealed with a correlation coefficient of 0.97 (p < 0.0001). Again, peak
      ejection rate and peak filling rate obtained from the 2020tc Imager data
      correlated well with those obtained from the Anger-type camera data (r = 0.93, p
      < 0.0001 and r = 0.80, p < 0.001, respectively). These data reveal that the
      2020tc Imager has an excellent data collection efficiency and a high reliability
      in assessment of left ventricular function. Thus, the solid-state gamma camera
      was thought to be a useful hardware in nuclear cardiology.

PMID- 11452493
TI  - [Clinical PET activities in European and Asia-Oceanian countries].
AB  - Clinical diagnosis using positron emission tomography (PET) requires high costs.
      Therefore, sociomedical evaluation is very important for spread of clinical PET.
      In this report, sociomedical situation in European and Asia-Oceanian countries,
      especially concerning transportation of 18F-FDG and reimbursement of medical
      costs for clinical PET indications, is reported. It seems that UK, Germany and
      Belgium are the most advanced in clinical PET in Europe. In these countries, many
      PET investigations are reimbursed though systems are different among the
      countries. In UK, both public and private insurance gives authorization for
      clinical PET to some extent. In Germany, private health insurance companies give
      authorization but public insurance has not. In Belgium, private health insurance
      does not exist and public insurance gives authorization for clinical PET. Other
      European countries seem to be in transitional stages. Transportation of 18F-FDG
      has been already started in almost every country in Europe and Asia-Oceania. In
      Japan, neither transportation of FDG nor full reimbursement of clinical PET has
      not started yet and this situation seems to be exceptional. To promote clinical
      PET in Japan, there is the need of at least establishing a list of clinical
      indications for PET investigations and establishing commercial-based 18F-FDG
      supplying system. They could be regarded as a kind of infrastructure for spread
      of clinical PET.

PMID- 11452494
TI  - [Anesthetic management for neurosurgery].

PMID- 11452495
TI  - [Carotid endarterectomy using a shunt system].

PMID- 11452496
TI  - [Reconstruction of the sellar floor during transnasal pituitary surgery using
      ceramics composed of a combination of hydroxyapatite and tricalciumphosphate].
AB  - Our clinical experience with reconstruction of the sellar floor during transnasal
      transsphenoidal surgery for pituitary tumors using ceramics composed of a
      combination of hydroxyapatite and tricalciumphosphate (pituitary plate) is
      described. A pituitary plate was used to reconstruct the sellar floor in 15
      patients with pituitary tumors that included 13 pituitary adenomas and 2 Rathke's
      cleft cysts. This method is indicated for cases of reoperation and cases in which
      there is of much cerebrospinal fluid leakage during surgery. This material is
      provided as a pituitary plate 12 x 12 mm round and 2 mm thick. There are four
      holes in the center by which the plate can be held with regular bipolar forceps.
      At the time of closing the sellar floor window, a pituitary plate was carved with
      scissors into a suitable shape and slipped inside the bony defect. The
      postoperative position of the pituitary plate could be clearly identified on
      skull roentgenogram and magnetic resonance imaging. No displacement or migration
      of the implanted pituitary plate was observed in any patient during follow-up
      radiological examinations. Infections such as a pituitary abscess or meningitis
      were not observed clinically or radiologically in any patient. In three patients
      who underwent repeated transnasal surgery for regrowth of the tumor, the
      pituitary plate that had been placed at the initial procedure was covered with a
      thin fibrous capsule and the plate was well preserved. These results indicate
      that a pituitary plate can be useful for reconstruction of the sellar floor in
      transnasal-transsphenoidal surgery.

PMID- 11452497
TI  - [Transparent imaging of CT angiography for the delineation of cerebral
      aneurysms].
AB  - Transparent imaging with volume rendering of CT angiography (CTA) was used to
      delineate cerebral aneurysms. Five unruptured cerebral aneurysms discovered
      incidentally on MR angiography were delineated as transparent CTA images and
      compared with routine three-dimensional CTA images. Reconstructing the volume
      data sets by adjusting the opacity level and range of CT values allowed
      transparent visualization of the aneurysm with its related vessels through the
      bony structures of the cranial base. Transparent imaging of CTA may be a useful
      adjunct for the evaluation of an aneurysm adjacent to the bony structure.

PMID- 11452498
TI  - [Neuro-Behcet disease mimicking a thalamic tumor].
AB  - A case of neuro-Behcet disease presenting as a thalamo-lenticular expanding
      lesion is reported. A 41-year-old female was admitted with mental deterioration
      and right hemiparesis. She had been suffering from recurrent oral and genital
      ulcers and erythema nodosum for several years before admission. Neurological
      examination on admission revealed poor mental activity, dysarthria and right
      hemiparesis. Lumbar puncture showed CSF pleocytosis. CT and MRI revealed a
      thalamo-lenticular expanding lesion. CT showed a homogeneous hypodense lesion of
      the left lenticulothalamic region, which was enhanced in the central part,
      exerting a mild mass effect. MRI also revealed the lesion better. The T2 weighted
      images showed a high intensity signal in the left thalamo-lenticular region and
      the left peduncle. The T1 weighted images showed a low signal in the
      corresponding areas with a central enhancement with Gd-DTPA. EEG, SPECT and
      angiography indicated normal findings. Histologic study of the brain biopsy
      tissue ruled out a tumor but did not show any specific diagnosis. The patient
      improved with steroid therapy. In conclusion, the clinical and radiological
      presentation of neuro-Behcet disease can mimic a cerebral tumor. In such cases,
      stereotactic biopsy is useful to exclude suspicion of a cerebral tumor.

PMID- 11452499
TI  - [A case of cardiac myxoma with multiple brain hemorrhage].
AB  - A case of cardiac myxoma with multiple brain hemorrhage is reported. A 57-year
      old male had complained of lower abdominal pain, diarrhea and fever for 3 days.
      On admission, he was in a condition of disseminated intravascular coagulation and
      sepsis. An abdominal CT scan showed infarction in the right kidney and spleen and
      an echocardiogram also showed myxoma in the left atrium. Although he presented no
      neurological symptoms, the brain CT showed multiple brain hemorrhage in the
      bilateral brain hemispheres. Total resection of the tumor was carried out for the
      improvement of the patient's general condition. Vimentin, S-100 protein and
      neuron specific enolase was positive in immunological staining and the
      pathological diagnosis was myxoma. Postoperative recovery of consciousness was
      poor and left hemiparesis developed. CT showed the increase of hematoma but
      angiography showed no cerebral aneurysm. The symptoms improved with conservative
      therapy. However the enhanced lesion remained in the right parietal lobe and an
      operation was performed 5 months later. The myxoma cell could not be found in the
      pathological examination, so tumor embolism, cerebral infarction, hemorrhagic
      infarction due to DIC, hematoma enlargement caused by heparinization during
      operation were suspected to have occurred in this order without tumor growth.

PMID- 11452500
TI  - [Spontaneous partial thrombosis of an unruptured peripheral, superior cerebellar
      artery aneurysm: a case report].
AB  - A 52-year-old female suddenly developed headache and dizziness. On admission she
      complained of gait disturbance with dizziness but cranial nerve palsy could not
      be detected. CT scan revealed a mild high density lesion in the right ambient
      cistern and the density of the lesion had become much higher 5 days after
      admission. MRI revealed a homogeneous iso-intense lesion on T1WI, T2WI 2 days
      after admission and the lesion had changed to homogeneous high. The lesion was
      suspected to be a fresh thrombus. Right vertebral angiography showed a part of
      aneurysm arising from the ambient segment of the right superior cerebellar artery
      and we diagnosed the lesion as a partially thrombosed superior cerebellar artery
      aneurysm. About forty cases of peripheral superior cerebellar artery aneurysm
      have been described in the literature, but cases of spontaneous thrombosis of the
      aneurysms have been very rare. Spontaneous thrombosis of aneurysms was usually
      thought to occur in large aneurysms, but the aneurysm in our case was not large.
      We suspected that in our case spontaneous thrombosis may have been caused by
      occlusion of the parent artery of the aneurysm.

PMID- 11452501
TI  - [A case of aneurysm of the peripheral middle cerebral artery undetectable on
      preoperative angiogram].
AB  - The authors describe a rare case of an aneurysm of the peripheral middle cerebral
      artery. A 63-year-old female with a past history of hypertension suddenly fell
      into a comatose state, and was brought to our hospital. On admission, CT scan
      showed intracerebral hematoma located in the right putamen with diffuse
      subarachnoid hemorrhage. To exclude vascular lesions, an angiography was
      performed just after admission. The right carotid angiogram showed an aneurysm at
      the cavernous portion of the internal carotid artery (ICA), but failed to show
      any aneurysms in the rest of the intracranial circulation. Just after the
      angiography, emergent operation was performed for the main purpose of evacuation
      of the hematoma, and with only the secondary purpose of searching for
      undetectable aneurysms. The patient underwent a right frontotemporal craniotomy.
      After partial evacuation of the hematoma through the corticotomy of the right
      frontal operculum, the Sylvian fissure was opened widely. No aneurysm was
      observed either in the main trunk of the right ICA or the middle cerebral artery
      (MCA). During the final stage of evacuation of the hematoma through the
      corticotomy, arterial bleeding occurred. While evacuating the blood, we detected
      a saccular aneurysm arising from MCA branch (M2-M3 junction) and we clipped the
      aneurysm. We discuss peripheral MCA aneurysms with a review of the literature.

PMID- 11452502
TI  - [A case of intrasellar meningioma mimicking pituitary adenoma].
AB  - The authors report a patient with a rare intrasellar meningioma mimicking
      pituitary adenoma. A 60-year-old man was admitted to our hospital for evaluation
      of general fatigue. He had no neurological deficit including visual function.
      Endocrinological tests revealed panhypopituitarism. The craniogram showed slight
      enlargement of the sella turcica with thinning of the dorsum sellae. CT scan and
      MR imaging demonstrated a homogeneously enhanced intrasellar mass with slight
      suprasellar extension. Partial removal of the mass was performed via the
      transsphenoidal approach because it was extremely firm and hemorrhagic.
      Histological diagnosis was transitional meningioma. The patient has been well for
      two years after surgery without tumor progression on MR imaging. It is mandatory
      to distinguish intrasellar meningioma from pituitary adenoma preoperatively
      because of marked difference in their treatment strategies. Despite recent
      advances in neurodiagnostic imaging, it may still be difficult to differentiate
      pituitary adenoma from intrasellar meningioma. When we re-evaluated the MR
      imaging, we recognized that the tumor had demonstrated specific findings, ruling
      out pituitary adenoma, namely bright and homogeneous enhancement, dense
      enhancement in the early phase on the dynamic MR study, and flow void signal
      within the mass. The authors emphasize that careful evaluations of MR imaging
      will allow the correct preoperative diagnosis in patients with intrasellar
      meningioma mimicking pituitary macroadenoma.

PMID- 11452503
TI  - [Bilateral carotid stenting for radiation-induced arterial stenosis].
AB  - We report a case of bilateral radiation-induced internal carotid artery (ICA)
      stenosis treated with stenting. A 67-year-old man experienced transient left
      hemiparesis several times, and it was diagnosed as a bilateral ICA stenosis by
      magnetic resonance angiogram (MRA) and cervical ultrasound sonogram (US). Ten
      years before, the patient had received radiation therapy (66 Gy) and radical
      resection for a squamous cell carcinoma (SCC) in the right infrapharyngeal space.
      A cerebral angiogram showed bilateral severe ICA stenosis (right; 90%, left;
      99%). We diagnosed this as radiation-induced ICA stenosis, and performed carotid
      angioplasty with a self-expanding stent. The post-operative course was uneventful
      and the patient was discharged without neurological deficits. Carotid
      endarterectomy (CEA) is difficult in the case of carotid artery stenosis due to
      radiation-induced arterial injury. Carotid stenting may be an alternative
      treatment for such a patient.

PMID- 11452504
TI  - [Use of the GDC for embolization of a tumor fed by a cavernous branch of the
      internal carotid artery].
AB  - Currently, embolization of small branches of the internal carotid artery (ICA)
      can be embolized through superselective microcatheterization, followed by the
      injection of liquid or particulate embolic materials. Often, however, a
      microcatheter cannot be placed in a stable enough position to allow an
      endovascular surgeon to perform a safe embolization, and the reflux of embolic
      agents into the main trunk of the ICA is a major concern. Meticulous technique
      and a detailed knowledge of the vascular anatomy of the cavernous sinus region
      are necessary to maximize devascularization of the lesion and to minimize the
      risk of complications. This report describes the case of a patient with a
      hypervascular tumor whose feeding vessel from the cavernous ICA was successfully
      occluded with polyvinyl alcohol (PVA) combined with a regular Guglielmi
      detachable coil (GDC). A 62-year-old woman had a left-sided petroclival
      meningioma, which was diagnosed based on computed tomography and magnetic
      resonance studies. Transfemoral angiographic studies demonstrated that the tumor
      was fed by intracavernous branches of the left ICA. We believed that another
      embolic agent would have presented a risk of reflux into the ICA, with possible
      unwanted occlusion of normal intracranial arteries. A single GDC was sufficient
      to occlude the feeding artery, and the patient underwent successful surgery 3
      days after the endovascular procedure. The GDC can eliminate the ICA supply to
      hypervascular tumors safely when liquid or particle embolic materials would
      present a risk of reflux into normal arteries. This device can be positioned and
      repositioned and can be detached without mechanical force. It may also decrease
      the risk of unwanted embolization of normal intracranial arteries.

PMID- 11452505
TI  - [Evaluation of dermatological symptoms of Yusho patients in the annual
      examination in 1999-2000].
AB  - We analyzed the severity grades of the skin symptoms of Yusho patients who
      visited the annual examinations in 1999 and 2000. The severity grades of the skin
      symptoms clearly improved. The patients graded as 0 increased and those graded as
      II.III-III or III.IV-IV decreased as compared to the data in 1993. The pattern of
      the skin severity scores did not change much, although the patients who showed
      0.1 reached 68% in 2000. The blood PCB concentration of Yusho patients also
      clearly decreased, especially in the patients who showed "A" pattern.
      Furthermore, the skin changes of the aged patients should be analyzed in detail
      in the future.

PMID- 11452506
TI  - [Mitogen-induced lymphocyte transformation in patients with Yusho].
AB  - To evaluate chronic immune effects of polychlorinated biphenyl (PCB), in vitro
      lymphocyte transformation in response to nonspecific mitogens were studied in 74
      patients with Yusho in 2000. Elevated response in phytohemagglutinin (PHA)
      induced lymphocyte transformation was detected in fifteen (20.3%) patients, while
      decreased PHA response was found in six (8.1%) patients. Concanavalin A (Con A)
      induced lymphocyte transformation was increased in six (8.1%) patients, and
      decreased in eleven (14.9%) patients. There were no significant correlations
      between blood PCB concentrations and lymphocyte transformation in response to
      PHA, Con A, or pokeweed mitogen (PWM). We conclude that abnormality of lymphocyte
      transformation in patients with Yusho is frequent, but it may not be associated
      with blood PCB concentration.

PMID- 11452507
TI  - [An epidemiologic examination on the prevalence of the periodontal diseases and
      oral pigmentation in Yusho patients in 2000].
AB  - An epidemiologic examination was carried out to reveal the prevalence of the
      periodontal diseases and oral pigmentation in patients with Yusho in 2000. The
      results obtained were as follows. 1) 63 patients out of 69 patients with Yusho,
      who were measured periodontal pocket depth according to Ramfjord' methods, had at
      least one tooth with periodontal pocket deeper than 3 mm. Similarly, 188 teeth
      out of a total 285 examined teeth showed periodontal pocket with more than 3 mm
      depth. 2) In this examination, intraoral sinus tracts stoma were observed in 9
      patients out of 70 patients. Radiographic examination and probing examination of
      pocket depth indicated that periapical lesions were involved in these intraoral
      sinus tract formation. 3) Oral pigmentation was observed in 46 out of 76 patients
      with Yusho. In this study, gingival pigmentation was most predominant among oral
      pigmentation. These results indicated that PCBs had yet affected the mechanism of
      oral pigmentation and metabolism of alveolar bone.

PMID- 11452508
TI  - [Examination of serum nitric oxide in Yusho patients].
AB  - In order to evaluate the influence of oxidative stress by PCB, we measured serum
      nitric oxide (NO) in Yusho patients by the Griess method, which detected nitrite
      (NO2-) formed by the oxidization of NO. Serum NO2- concentrations were
      significantly increased in Yusho patients as compared to healthy controls, but no
      correlation was detected between serum NO2- concentration and PCB or PCQ level in
      Yusho patients. The relationship was analyzed between serum NO2- concentration
      and certain parameters such as clinical symptoms, habits and clinical data. Serum
      NO2- level had a positive correlation with CPK in male patients, but not in
      female and all Yusho patients. Furthermore, no mutual relation was detected
      between serum NO2- concentration and the other parameters such as blood pressure,
      smoking and each laboratory data. Therefore, the possibility is considered that
      Yusho is one of the diseases which show the increase of serum NO.

PMID- 11452509
TI  - Association between blood concentration of polychlorinated biphenyls and
      manifestations of symptoms and signs in chronic "Yusho" patients from 1986 to
      1997.
AB  - To examine the association between blood PCB level and manifestations of symptoms
      and signs by Yusho patients, a cross-sectional study was conducted using the
      results of nationwide health examination for Yusho. The subjects were the
      officially identified Yusho patients who admitted the health examination from
      1986 to 1997. The number of examinees with known blood PCB level was 334 in 1986,
      and decreased to 214 in 1997. The numbers of male and female patients were
      similar. The geometric mean (95% confidence interval) of blood PCBs concentration
      was 4.05 ppb (3.75 to 4.37) in 1986 and 2.85 ppb (2.63 to 3.08) in 1997. Multiple
      logistic regression analysis was carried out for the data of each year with log
      transformed blood PCB level as an explanatory variable and a manifestation of a
      sign or symptom as a response variable. Sex and age adjusted odds ratio and
      significance level (P) were computed. Positive association of blood PCB level
      with manifestations of comedones on the trunk and acneiform eruptions on the
      genital and gluteal regions was statistically significant for five, eight and six
      times, respectively. No other symptoms or signs showed such strong associations.
      Associations between manifestations of these signs and blood PCB level, however,
      did not seem to diminish in the twelve years of observation. It is suggested that
      the positive association of these signs with blood PCB level will still be
      maintained.

PMID- 11452510
TI  - [Detection of underlying causes of death among the deceased of Yusho patients by
      linkage to the national vital statistics data].
AB  - As of January 31, 1996, 292 deaths among registered patients of Yusho were
      identified by three follow-up studies conducted in 1986, 1990, and 1996. In this
      study, we attempted to identify underlying causes of death by linkage of the
      registered data to the National Vital Statistics Data provided by the Management
      and Coordination Agency of Japan, which included 15 million deaths between 1978
      and 1996. The two datasets were linked by matching for six variables; birth
      year/month/day, death year/month, and sex, along with a variable of death day or
      death place, or both. The matched cases were 203 among 235 deaths between 1978
      and 1996 (matching rate was 86%). Among the 203 deaths, 58 underlying causes of
      death were newly identified, 146 causes of death were already grasped by the
      follow-up studies, and 31 deaths did not have matching pair in the National Vital
      Statistics data. Among the 146 deaths, 110 causes of death were concordant with
      each other, however, 35 causes of death were completely discord. The reason of
      the discordance and the unmatched deaths might be due to difference in
      information of the matching variables in the two datasets. In order to conduct an
      efficient follow-up study of Yusho patients, identification of underlying causes
      of death by linkage to the National Vital Statistics Date is evitable. For that,
      we need to substitute basic information in the Yusho database to those compatible
      to the National civil registration system.

PMID- 11452511
TI  - [Follow-up survey of dioxins in the blood of Yusho patients (in 1998-1999)].
AB  - Follow-up survey of the blood concentration of PCDDs, PCDFs and non-ortho
      chlorine substituted PCBs in Yusho patients is very important for their health
      control. We determined the blood concentration of these dioxin isomers in 119
      blood samples collected in 1998 and 1999 using by a high-resolution gas
      chromatograph/high-resolution mass spectrometry (HRGC/HRMS). Thirty years had
      passed since the Yusho occurrence, and the total blood concentrations of PCDFs in
      the blood of Yusho patients were still as high as ever, except the patients with
      the PCB pattern C. Among the different groups of PCB patterns, the concentration
      of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF showed significant
      differences, excluding the group BC because of the small number of cases. The
      findings indicate that these isomers are not decomposed in human body since they
      had highly contaminated the causal rice oil at the onset. In typical Yusho
      patients (Group A of PCB pattern), the mean TEQ concentrations of PCDDs, PCDFs
      and non-ortho-chlorine substituted PCBs in the blood collected in 1998 were 21,
      206, and 14 pg-TEQ/g lipid, respectively, and in 1999, 30, 308 and 14 pg-TEQ/g
      lipid, respectively. The toxic contribution rate of PCDFs TEQ was still at high
      levels for total TEQ in both years. The patients of the group C, however, the
      mean blood levels of the dioxins TEQ in 1998 and 1999 did not differ from those
      of the normal controls determined in 1996 although some patients in this group
      showed a high toxic contribution rate of PCDFs TEQ for total TEQ. We will try the
      PCB isomer specific analysis of the Yusho patients blood, and will investigate
      the difference from normal controls blood.

PMID- 11452512
TI  - [The changes of PCBs and PCDFs as well as symptoms in Yusho patients for 30
      years].
AB  - Two mass-food poisonings called Yusho and Yucheng occurred in Western Japan and
      Taiwan in 1968 and 1979, respectively. Blood samples from 5 Yusho patients and 3
      Yucheng patients were collected several times from 1982 to 1998 and from 1980 to
      1995, respectively, and analyzed for PCB and PCDF congeners. Fat base
      concentrations of 2,3,4,7,8-penta-CDF in the Yusho patients, which were
      responsible for about 70% of the dioxin toxicity, are estimated to be decreased
      from 60 ppb in 1969 to 0.8 ppb in 1997 with the median half-life of 2.9 years in
      the first 15 years after the onset and 7.7 years in the next stage of 15 years.
      Fat base concentrations of total PCBs in the blood of Yusho patients are
      estimated to be decreased from 75 ppm just after the onset to 2.3 ppm after
      passage of 30 years. Typical Yusho symptoms of acneiform eruption, dermal
      pigmentation and increased eye discharge were very gradually recovered with lapse
      of ten years. However, enzyme and/or hormone mediated sign of high serum
      triglyceride, high serum thyroxin, immunoglobulin disorder and others are
      persistently maintained for 30 years.

PMID- 11452513
TI  - [Assessment of hydroxylated metabolites of polychlorinated biphenyls and
      polychlorinated dibenzofurans as potential estrogens by yeast two-hybrid system].
AB  - The estrogenic activities of several hydroxylated metabolites of PCBs and PCDFs
      were investigated by yeast two-hybrid assay based on the ligand-dependent
      interaction of estrogen receptor with coactivator. For the hydroxylated PCBs, the
      order of estrogenic potency was 4-OH-2',4',6'-triCB > 4-OH-4'-monoCB, 4-OH
      biphenyl. These compounds were evaluated as 10(3) to 10(4) less potent than 17
      beta-estradiol based on the concentrations of test compounds showing 10% activity
      of 10(-7) M 17 beta-estradiol. 2-OH-3',4,4'-triCB, 4-OH-2',3,4'-triCB and 3-OH-/4
      OH-2,2',5,5'-tetraCB, the metabolites of 2,2',5,5'-tetraCB were inactive as
      estrogens at the highest concentrations used in this study (10(-5) M). Also 4-OH
      3,3',4',5-tetraCB, the metabolite of 3,3',4,4'-tetraCB was inactive as estrogen,
      indicating that this hydroxylated metabolite did not take part in the estrogenic
      activity of 3,3',4,4'-tetraCB. OH group at 4-position of biphenyl was necessary
      for the expression of estrogenicity, but one or two chloro-substitution adjacent
      to OH group inhibited the activity. For the hydroxylated PCDFs, 8-OH-2-monoCDF, 7
      OH-3,4-diCDF, 8-OH-3,4-diCDF, 8-OH-3,4,6-triCDF and 3,8-(OH)2-2-monoCDF exhibited
      estrogenic activity. The estrogenic activity of 3,8-(OH)2-2-monoCDF was
      comparable to those of 4-OH-2',4',6'-triCB and 4-nonylphenol (mixture of
      compounds with branched sidechain). The order of activity was 3,8-(OH)2-monoCDF >
      8-OH-3,4-diCDF, 7-OH-3,4-diCDF > 8-OH-2-monoCDF, 8-OH-3,4,6-triCDF. These
      compounds were evaluated as 2.5 x 10(3) to 3 x 10(4) less potent than 17 beta
      estradiol. On the other hand, no estrogenic activity was observed for 2-OH
      dibenzofuran, 3-OH-2,8-diCDF, 6-OH-3,4-diCDF and 9-OH-3,4-diCDF at concentrations
      as high as 10(-4) M. Substitution of OH group at 2(8)- or 3(7)-position of
      dibenzofuran and no chloro-substitution adjacent to OH group was required for the
      estrogenic activity.

PMID- 11452514
TI  - [Species differences in the in vitro metabolism of 2,4,5,2',3',4'
      hexachlorobiphenyl].
AB  - In vitro Metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl (CB138) was studied
      using liver microsomes from rats, hamsters and guinea pigs. Guinea pig liver
      microsomes formed four metabolites named as M-1, M-2, M-3 and M-4 and these
      metabolites were all increased to about 4-5 fold of untreated microsomes by
      pretreatment of phenobarbital. Liver microsomes of rats and hamsters showed much
      less activity to metabolize CB138 than those of guinea pigs. Only phenobarbital
      treated microsomes produced very small amounts of M-3 in rats and M-1, M-2 and M
      3 in hamsters, but untreated and MC-treated microsomes did not. When mass spectra
      of the methylated derivatives of M-1, M-2, M-3 and M-4 were measured in GC/MS,
      the former two possess the molecular ion of 354 and the latter two had the
      molecular ion of 388. In addition, the mass fragmentation pattern indicated that
      M-1, M-2, M-3 and M-4 are 2-OH-4,5,2',3',4'-pentachlorobiphenyl, 5-OH
      2,4,2',3',4'-pentachlorobiphenyl, 3-OH-CB138 and 2-OH-3,4,5,2',3',4'
      hexachlorobiphenyl, respectively. Of four metabolites, the chemical structures of
      M-3 and M-4 were supported by the synthesized authentic compounds. From these
      results, it is suggested that the metabolism of CB138 in guinea pig liver
      proceeds mainly via 2,3-epoxide as an intermediate and a PB-inducible P450,
      CYP2B18, is the most important isozyme in CB138 metabolism.

PMID- 11452515
TI  - Effect of dioxins in mother's milk on sister chromatid exchange frequency in
      infant lymphocytes.
AB  - Sister chromatid exchange (SCE) frequency which was an index to the synthetic and
      sharp genetic toxicity was examined using the infant lymphocyte cells around
      postnatal of 1 year. SCE frequency as the control culture which was treated with
      the solvent, DMSO, alone (SCEcontrol) was 8.2 +/- 0.9/cell and as cultured with
      7,8-benzoflavone (ANF) (SCEANF) was 11.8 +/- 1.4/cell. In addition, the
      difference of SCEANF and SCEcontrol, namely, delta SCEs became 3.6 +/- 1.3/cell.
      The concentration of the dioxins in the mother's milk, which had taken by the
      infants, in the 2-4 month postpartum was 0.95 +/- 0.51 pg-TEQ/g in the male
      infants, and 0.97 +/- 0.48 pg-TEQ/g in the female ones. The sex difference could
      not be recognized in contamination levels of the dioxins in mother's milk. The
      SCE frequency of the infant lymphocytes was examined in order to evaluate the
      genetic toxicity of the dioxins which had contaminated mother's milk. As the
      result, either the SCE frequencies or delta SCEs did not show any significant
      correlation to the dioxins. Therefore, the dioxins were considered not to induce
      the genetic toxicity such as the SCEs at the present levels of pollution in
      Japanese mother's milk around postnatal of 1 year.

PMID- 11452516
TI  - [Influential factors in the elevation of serum creatine phosphokinase for the
      patients with Kanemi Yusho--freeze fracture study of rat muscle plasma membrane].
AB  - We studied the factors of the elevation of serum creatine phosphokinase (CK)
      using the data from the routine medical checkup of Kanemi Yusho patients during
      1995 and 1999. We also studied rat muscle plasma membrane by the freeze fracture
      method, which were given the polychlorinated biphenyls (PCB) and controls. The
      patients with elevation of serum CK showed significant elevation of PCB in their
      blood but not in polychlorinated quanterphenyls (PCQ). The rat muscle plasma
      membrane showed a slight increase of orthognal array density but it was not
      statistically significant. The densities of caveolae and particles were not
      changed. Accordingly, PCB were thought to be a factor in the elevation of CK in
      the serum.

PMID- 11452517
TI  - Effects of a highly toxic coplanar polychlorinated biphenyl, 3,3',4,4',5
      pentachlorobiphenyl on intermediary metabolism: reduced triose phosphate content
      in rat liver cytosol.
AB  - The effects of a highly toxic coplanar polychlorinated biphenyl, 3,3',4,4',5
      pentachlorobiphenyl (PenCB), on triose phosphate metabolizing enzymes were
      studied. Male Wistar rats received 25 mg/kg PenCB, i.p. At this dose the compound
      provokes a wasting syndrome. The activity of triose phosphate metabolizing
      enzymes, glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase,
      glycerokinase, transaldolase and transketolase were significantly reduced by
      PenCB treatment to 50%, 60%, 50%, 70% and 40% of free-fed controls, respectively.
      An inhibition study with pyrazol, a specific inhibitor of alcohol dehydrogenase
      (ADH), showed that ADH makes about a 30% contribution to the formation of
      glycerol-3-phosphate from glyceraldehyde-3-phosphate. Our current study revealed
      that PenCB suppresses ADH at the protein expression level. The reduced formation
      of glycerol-3-phosphate from glyceraldehyde dehydrogenase by PenCB could be due
      to the suppression of ADH. The triose phosphate content in the liver cytosol of
      PenCB-treated rats was significantly lower than in free-fed controls. The
      suppression of triose phosphate metabolism could be a cause of the wasting
      syndrome provoked by highly toxic coplanar PCB.

PMID- 11452518
TI  - [Suppression of stress proteins, GRP78, GRP94, calreticulin and calnexin in liver
      endoplasmic reticulum of rat treated with a highly toxic coplanar PCB].
AB  - The present study was addressed on the effect of 3,3',4,4',5-pentachlorobiphenyl
      (PenCB) to the expression of molecular chaperon proteins, glucose regulated
      protein (GRP) 78, GRP94, calreticulin and calnexin in liver endoplasmic reticulum
      of rat by treatment with acute exposure. Male Wistar rats received PenCB in corn
      oil at once a dose of 10 mg/kg i.p., then at 5 days after treatment the
      microsomes were prepared. Free-fed and pair-fed control groups were given the
      vehicle. The microsomal proteins were separated on SDS-PAGE, transferred to
      membrane and blotted using antibody towards respective chaperone proteins. The
      protein levels of GRP78, GRP94, calreticulin and calnexin were significantly
      decreased with the acute exposure. In addition, albumin level in the microsomes
      was also significantly reduced by the PenCB treatment. The transferrin level was
      significantly higher than pair-fed but not from free-fed group. These chaperone
      proteins have important physiological functions against synthesized and/or
      denatured proteins, which include assembling, folding of proteins. PenCB
      treatment may alter the extent of biosynthesis of secretory protein such as
      albumin through the decreasing levels of chaperone proteins in endoplasmic
      reticulum. Interestingly, reduced GRP78 protein level by PenCB was not due to
      decreased mRNA level. Our results suggested that a part of the toxicity of PenCB
      is associated to significant decrease of the chaperone proteins in the
      endoplasmic reticulum.

PMID- 11452519
TI  - [The feasibility of a limited operation for primary lung cancer].
AB  - We reviewed 33 patients who underwent a limited operation for primary lung cancer
      between 1980 and 1998. These cases were divided into three groups; a poor risk
      group consisting of 18 patients who had a high risk such as pulmonary or cardiac
      dysfunction and who underwent partial resection of a lung, a reduction group
      consisting of 9 patients who had advanced lung cancer or uncontrolled cancer of
      an organ other than the lung and who underwent partial resection, and an active
      limited operation group consisting of 6 patients who underwent segmentectomy with
      lymphoadenectomy for the treatment of early lung cancer. The 1 and 3-year
      survival rates in the poor risk group, reduction group and active limited
      operation group were 73.9, 60.0, 100%, and 63.4, 0.0, 100%, respectively. The
      results of limited operations performed for poor risk cases were satisfactory in
      terms of both functional state and prognosis. Limited operations performed to
      reduce tumor in advanced lung cancer cases did not improve the prognosis.
      Although an active limited operation for a case of early lung cancer remains
      controversial with respect to indication, it is thought that this operation is
      not inferior to a standard radical operation (lobotomy with mediastinal
      lymphoadenectomy) in selective cases in which the maximum tumor diameter is 2 cm
      or less. The indication for a limited operation must be further examined from
      aspects of tumor size, tumor histology and the other factors of the tumor.

PMID- 11452520
TI  - [Endoventricular circular patch plasty (dor operation) for postinfarction left
      ventricular aneurysm and ischemic cardiomyopathy].
AB  - The determination of purse-string suture line is one of the most important point
      in endoventricular circular patch plasty (Dor operation) for postinfarction left
      ventricular aneurysm (LVAN), especially for ischemic cardiomyopathy (ICM). We
      suggest following three points to decide appropriate suture line. First, the
      purse-string suture on the basal side should be placed on the 1-2 cm level under
      diagonal branch. Secondly, lateral wall should not be over excluded to maintain
      left ventricular function. And the third, akinetic or dyskinetic lesion of apex
      and septal wall should be excluded as much as possible. Nine cases of five LVAN
      and four ICM were underwent Dor operation in our institute from Dec. 1999 to Jan.
      2000. All patients were weaned from cardiopulmonary bypass easily except one
      patient, who was operated under IABP support, because of his preoperative severe
      heart failure. All patients recovered well without any serious complications and
      postoperative left ventricular graphies were satisfactory. Left ventricular
      ejection fraction and stroke volume index were increased from 34 +/- 17 to 55 +/-
      16% and from 38 +/- 7 to 47 +/- 6 ml/m2, end-diastric and systric volume index
      decreased from 141 +/- 37 to 88 +/- 19 ml/m2 and from 96 +/- 41 to 41 +/- 23
      ml/m2 respectively. The Dor procedure adopted our idea led to satisfactory result
      in hemodynamic and also in morphologic study.

PMID- 11452521
TI  - [Assessment of left internal thoracic artery graft by exercise Doppler
      echocardiography].
AB  - Doppler echocardiography has several advantages such as frequent use, noninvasive
      approach, and physiological evaluation. Supine bicycle exercise testing was
      conducted for 30 patients undergoing CABG with LITA to LAD. Doppler
      echocardiography studies were performed before and after exercise to observe the
      change. On the basis of the angiographic data, patients were divided into two
      groups: 27 patients with a patent LITA graft, 3 patients with mildly stenosed
      LITA graft. In the patients who had patent grafts, diastolic flow velocity were
      increased higher than systolic after exercise. In the stenotic group, the flow
      pattern was changed to further systolic one. Doppler echocardiography during
      exercise is thought to be a reliable method to assess the LITA flow.

PMID- 11452522
TI  - [Serum cytokine levels response to cardiac surgery with cardiopulmonary bypass].
AB  - The response of tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6),
      interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist
      (IL-1ra), macrophage colony stimulating factor (MCSF), white blood cell (WBC),
      platelet (Plt), lactic acid (LAC) to cardiopulmnary bypass (CPB) were studied
      until 48 hours after aortic declamping in 11 patients who underwent elective CABG
      (n = 4), mitral valve plasty or replacement with modified maze procedure (n = 5),
      and both procedures (n = 2). The highest levels of the cytokines IL-6, IL-8, IL
      10, and IL-1ra were observed after the removal of the cross clamp. These
      cytokines just after the aortic declamping are likely to be occurred not only by
      an interaction of the blood components with the artificial surfaces, but also by
      ischemia-reperfusion injury upon discontinuation of the aortic clamping. MCSF
      increased gradually in the late post-CPB phase and reached a peak at 48 hr after
      aortic declamping. MCSF may play an important role in regulating hematopoiesis on
      the postoperative days 1 and 2 in patients. In conclusion, the therapy based on
      the kinetics of these cytokines would be useful for patients undergoing CPB.

PMID- 11452523
TI  - [Endoscopic transthoracic sympathectomy (ETS) with a fine 2-mm thoracoscope in
      palmar hyperhidrosis].
AB  - Endoscopic transthoracic sympathectomy (ETS) is an efficient, safe, minimally
      invasive procedure, and requires only a short period of hospitalization. We
      performed bilateral ETS using a thoracoscope 2 mm in diameter. We performed 120
      ETS for the treatment of palmar hyperhidrosis from August 1997 to April 2000. The
      patient was placed in the semi-sitting position under general anesthesia, one
      lung ventilation being used; the operation was performed with 2-mm two-puncture
      method. The sympathetic chain could be observed through parietal pleura riding on
      the costovertebral junctions. A 2-mm Kirschner wire was employed as an electrode,
      and the second and third thoracic sympathetic chains were electro cauterized. A
      thoracic drain was not used. The needling sites were only 2 mm in size and could
      be fixed without suture. For the patient, a small scar of this size means
      virtually no scar. The operative times were from 11 min to 81 min in bilateral
      ETS. Immediately and dramatic decrease in the sweat excretion in the palms was
      noted in all patients. The 95% patients were highly satisfied with the results.
      The commonest side effects were compensatory sweating. This procedure is
      recommended as the method of choice for the surgical treatments of palmar
      hyperhidrosis.

PMID- 11452524
TI  - [Evaluation for factors associated to early tracheal extubation after coronary
      artery bypass grafting].
AB  - Recent studies suggest that early tracheal extubation after coronary artery
      bypass grafting (CABG) may reduce intensive care unit use and cost. During recent
      two years, 96 patients were underwent CABG under cardiopulmonary bypass by low
      dose fentanyl and isoflurane anesthesia. We compared two groups of patients for
      evaluation of factors associated to early tracheal extubation. 47 cases (Group A)
      were extubated within six hours (average 4.4 hrs) following operation, and 26
      cases (Group B) were extubated later than twelve hours (average 57.5 hrs). It is
      suggested that emergency cases, female, elderly patients, dysfunction of kidney
      and long operation time associated to late extubation. But early extubation after
      CABG does not increase perioperative morbidity except for the cases that fell in
      low cardiac output syndrome or postoperative respiratory complications.

PMID- 11452525
TI  - [Experience of pediatric cardiac transplantation in the Cleveland Clinic
      Foundation].
AB  - Brain death was not approved on the patients under 6 years old in Japan now. It
      is impossible to perform cardiac transplantation on the small children. Between
      October 1997 and November 1998, cardiac transplantation was performed by
      pediatric cardiac surgical team in 11 children at the Cleveland Clinic
      Foundation. 7 patients were cardiomyopathy under 18 years old and 4 were
      congenital heart diseases in all ages. 8 were status 1 and 2 were requiring
      extracorporeal membrane support. Bicaval technique was exclusively utilized.
      There was one early death due to multiple organ failure. 10 patients underwent
      myocardial biopsy and the half of them had more than 3 A rejection. These acute
      rejections were controlled with steroid pulse therapy and OKT-3 treatment. We
      took part in the management of patients with pediatric cardiac transplantation at
      the Cleveland Clinic Foundation. Practical patient cares were described in this
      report.

PMID- 11452526
TI  - [Two cases of stent graft repair for thoracic aortic dissection: usefulness of
      three-dimensional computed tomogram].
AB  - We carried out stent graft repair in two patients with Stanford type B thoracic
      aortic dissection. A 51-year-old male was admitted to our hospital because of
      thoracic aortic dissection. Chest CT revealed an aneurysm of the distal aortic
      arch. The entry was pointed out 1 cm distal from the take off of the left
      subclavian artery in three-dimensional CT (3 D-CT). He was treated with a
      Gianturco stent which was anchored into the 30 mm Hemashield graft under
      selective cerebral perfusion. Another case was a 72-year-old male with a
      descending aortic aneurysm. 3 D-CT showed that the entry existed 4 cm proximal to
      the celiac artery. We performed transluminal implantation of the spiral Z-stent
      covered with the woven Dacron graft. 3 D-CT was useful for the preoperative
      management and the surgical treatment of thoracic aortic dissection.

PMID- 11452527
TI  - [Incomplete resection for primary non-small cell lung cancer].
AB  - A superior outcome is observed for cases of complete resection compared with that
      of incomplete resection. The reason and the countermeasure of the incomplete
      resection for lung cancer were analyzed. During 12 years, 274 patients with
      primary non-small cell lung cancer were surgically treated. Two hundred and forty
      eight patients underwent complete resection and 26 incomplete resection. Three
      year survival was 62% for patients with complete resection and 17% for patients
      with incomplete resection. Survival rates were not different between the
      paroative reduction surgery and the exploratory thoracotomy. Tiny but multiple
      pleural dissemination or small amount of the malignant pleurfal effusion was not
      able to detect preoperatively. In these cases, preoperative thoracoscopic
      observation may useful for avoiding the meaningless thoracotomy. Postoperative
      radiochemotherapy may improve the prognosis if the therapy is effective.
      Chemotherapy on the basis of the sensitivity assay is warranted.

PMID- 11452528
TI  - [Evaluation of therapeutic method for malignant tumors involving the tracheal
      carina].
AB  - We evaluated 9 patients with malignant tumors involving the tracheal carina. In 2
      patients, carinal reconstruction was performed using Miyamoto's method and sleeve
      pneumonectomy was performed in another patient. All 3 patients had no anastomotic
      complications after the operation and were ambulatory at discharge. Two patients
      are still alive, and the others died by 15 months after surgery. Dynamic stenting
      was performed in 4 patients and a Dumon stent was used in 2 patients. Respiratory
      symptoms were relieved soon after stent placement, but none of the stented
      patients survived more than 3 months, except for one who also had surgery.
      Sometimes surgery is avoided because of its high morbidity and mortality, but the
      prognosis is very poor without resection. We think surgery should be performed
      where possible, when the disease is resectable. Miyamoto's method is superior to
      others and causes few complications.

PMID- 11452529
TI  - [A case of minimal invasive aortic valve replacement for quadricuspid aortic
      valve with aortic regurgitation].
AB  - Congenital quadricuspid aortic valve is rare, which may be a cause of sever
      aortic regurgitation. We report a case of a 55-year-old man who had severe aortic
      regurgitation with congenital quadricuspid aortic valve. Preoperative aortography
      showed severe aortic regurgitation. Preoperative trans-esophageal
      echocardiography revealed abnormal quadricuspid aortic valve. We performed
      minimal invasive aortic valve replacement with SJM # 21 mm HP prosthetic valve
      through the limited upper sternotomy. Skin incision was 9 cm. Aortic cross
      clamping time was 92 min, cardiopulmonary bypass time was 108 min. At the
      operation, a quadricuspid valve with three equal cusps and one small cusp was
      noted. The postoperative course was excellent and he discharged 8 days after the
      operation.

PMID- 11452530
TI  - [A case of combined operation of aortic valve slicing and root remodeling for
      ascending aortic aneurysm with aortic regurgitation].
AB  - A 56-year-old female admitted with severe back pain, and her chest computed
      tomography demonstrated non-dissecting sclerotic aneurysm of the ascending aorta.
      Aortography and echocardiography showed marked dilatation of the ascending aorta
      and the Valsalva sinuses resulting in disappearance of the sinotubular junction.
      Aortic regurgitation of grade three was, also, recognized. A combined operation
      of aortic valve slicing of the right and the left coronary cusps and aortic root
      remodeling (Yacoub's method) was successfully performed. A woven Dacron double
      veloured graft (Hemashield) of 22 mm in diameter was used for reconstruction of
      the ascending aorta and its root. Postoperative aortography figured the new
      sinotubular junction and the new Valsalva-like sinus composed by the graft, and
      aortic regurgitation was controlled to grade one.

PMID- 11452531
TI  - [A case of isolated tricuspid regurgitation caused by a dilated tricuspid annulus
      treated by ring annuloplasty].
AB  - Isolated tricuspid regurgitation is rare. A 64-year-old man was admitted to our
      hospital with a complaining of shortness of breath and edema of lower
      extremities. Chest X-ray showed remarkable cardiomegaly (cardiothoracic ratio,
      73%). Echocardiogram demonstrated severe tricuspid regurgitation and dilated
      right atrium. At operation, the tricuspid annulus was severely dilated about 7 cm
      in diameter, and all leaflets of tricuspid valve were intact. Prosthetic ring
      annuloplasty with a 32 mm Carpentier-Edwards ring was performed. Postoperative
      course was uneventful. Four weeks after operation he was discharged from the
      hospital and he is now leading a normal life. Careful follow up for long time is
      essential in this case.

PMID- 11452532
TI  - [A case of permanent pacemaker implantation in small infant using steroid-eluting
      epicardial pacing lead: changes of the pacing threshold in acute phase].
AB  - A 1-year-old infant with complete atrioventricular block was successfully treated
      with the pacemaker implantation using steroid-eluting epicardial pacing lead by
      the subxyphoid approach. Pacing threshold after implantation were measured
      frequently to use the function named "Capture management" of the generator
      (Medtronic: Kappa, Model 701). The postoperative pacing threshold were kept lower
      and stabilized after 5 weeks.

PMID- 11452533
TI  - [A case of schwannoma arising in brachial plexus with intrathoracic extension].
AB  - A case of benign schwannoma arising in the brachial plexus with intrathoracic
      extension was presented. The patient was a 55-year-old man, who was pointed out
      an abnormal shadow in the left apical region on routine chest X-ray examination.
      MRI showed that the mass extended to the lowest trunk of the brachial plexus. He
      had no complaint. Therefore, a diagnostic operation was performed. The tumor was
      subcapsularly resected with thoracoscopic surgery. Histopathological examination
      revealed a schwannoma (Antoni type A and B). It should be kept in mind that
      tumors arising in the brachial plexus are a probable differential diagnosis for
      tumors at the pulmonary apex, even if no neurological symptoms are seen in the
      upper extremities.

PMID- 11452534
TI  - [Complete transection of the left main bronchus due to a blunt chest trauma:
      report of a case].
AB  - A 62-year-old man was injured in a traffic accident. A chest roentgenogram showed
      pneumothorax, hemothorax, subcutaneous and mediastinal emphysema, multiple rib
      fractures, and a shift of the trachea to the right. Bilateral thorax drainage was
      performed, and air leakage from a left chest tube was observed. A chest computed
      tomogram demonstrated stenosis and deformation of the left main bronchus.
      Bronchofiberscopy revealed complete obstruction of the left main bronchus by the
      left main pulmonary artery. An emergency thoracotomy revealed complete
      transection of the left main bronchus and laceration. End-to-end anastomosis of
      the left main bronchus was performed with interrupted 4-0 PDS II suture. The
      patient was discharged at the 33rd hospital day.

PMID- 11452535
TI  - [A case of pneumonectomy for lung cancer associated with scleroderma].
AB  - A 60-year-old female, diagnosed as scleroderma, was referred to our hospital
      because of symptoms of common cold and abnormal findings on a chest X-ray. The
      chest X-ray and CT scan revealed a mass in the left upper field, suspected to
      invade left anterior chest wall. Moreover, fibrotic changes were observed in the
      lung field. Cytology by bronchofiberscopy showed squamous cell carcinoma.
      Evaluation of pulmonary function, including unilateral pulmonary artery occlusion
      test (UPAO), revealed possibility of lung resection. Subsequently, pneumonectomy
      with combined resection of left 1st rib was performed. Postoperative course was
      uneventful and she was discharged. She was admitted again four months after the
      operation with appetite loss and body weight loss. Further examinations revealed
      arrhythmia, renal failure, pancreatitis and liver metastasis. Her general
      conditions grew worse and she died five months after the operation. In
      conclusion, UPAO was a useful method to determine the functional lung
      resectability for the case with scleroderma. However, effects of surgical stress
      for the development of scleroderma remain to be elucidated.

PMID- 11452536
TI  - [Recurrence and pulmonary metastasis of extradural paraganglioma in thoracic
      vertebral canal: report of a case].
AB  - A 70-year-old female was operated on for extradural spinal cord tumor in 1982.
      Microscopic examination revealed the tumor as paraganglioma. Tumor recurred at
      paravertebral twice in 1985 and 1989, and they were also resected. In 1995, her
      chest X-ray film showed round tumor in the right upper field. Exploratory open
      lung biopsy was performed in 1996, and right upper lobectomy was performed
      according to for malignant lung tumor because intra-operative microscopic
      findings showed carcinoid or lung metastasis of paraganglioma. Chest wall tumor
      at paravertebral was resected at the same time. Postoperative microscopic
      examination revealed the tumors were same as operated paraganglioma. The 2nd
      thoracotomy was done in 1999, and two chest wall tumors and a pulmonary nodule in
      right S8 segment were resected. They were recurrence and pulmonary metastasis of
      paraganglioma. Now 18 years after initial operation, she is out of hospital in
      tumor free.

PMID- 11452537
TI  - [Electrophysiological tests in clinical laboratory].
AB  - We briefly described recently developed methods for testing cardiac
      electrophysiological phenomena such as 24-hour Ambulatory ECG, high resolution
      ECG, body surface mapping ECG, heart rate variability, QT and QT dispersion, and
      T wave alternans. Of these methods ambulatory ECG monitoring is important and
      useful for detecting malignant arrhythmias and ischemia attacks, especially in
      cases of vasospastic angina. Using this method, it is possible to quantitatively
      analyze arrhythmia and elucidate the pathophysiology of vasospastic angina. The
      monitoring system is useful not only for diagnosis, but also for assessing
      treatment efficacy. Heart rate variability is currently used for analyzing the
      autonomic nervous system; however, the exact meaning of each index still remains
      to be confirmed. The concept of QT dispersion was recently introduced as an index
      for detecting dispersion of ventricular repolarization and QT dispersion is still
      controversial. T wave alternans monitoring has been recently introduced as a new
      method of assessing the microvolt level of T wave alternans, which has been
      hypothesized to correlate with the occurrence of arrhythmic events in myocardial
      infarction. The possible roles of these methods and their applications for
      clinical practice are discussed.

PMID- 11452538
TI  - [Topics of clinical physiological tests--pulmonary function--proposal of physio
      chemical tests].
AB  - Pulmonary functions are classified as respiratory and non-respiratory. Although
      the mechanisms of non-respiratory pulmonary function have already been
      established, no new tests of respiratory pulmonary function have been developed
      for a long time. Thus, we report here a new analytic test of respiratory
      pulmonary functions. The new analytic method is physio-chemical analysis, in
      which the chemical factors of lungs are estimated from the physiological
      characteristics of lung during respiration. As examples, this report shows the
      method of exchanging mechanical energy to chemical energy in a comparison of lung
      ventilatory work between smokers and non-smokers. This report discusses the
      relationship between chemical energy and ATP in the blood of pneumoconiosis
      patients.

PMID- 11452539
TI  - [Measurement of biochemical components in individuals with infrared
      spectroscopy].
AB  - We have developed the Fourier transform infrared spectral analysis system to
      measure constituents of human oral mucosa in vivo and clinically obtained serum
      for non-invasive diagnosis. The attenuated total reflectance(ATR) probe in rod
      shape was used for the measurements of both oral tissue and serum. The results
      indicate that the change of in vivo oral mucosal infrared spectra correlated with
      that of blood triglyceride level, and rapidly analyzed by artificial neural
      networks successfully. The serum glucose level was correlated with glycan-related
      infrared bands, although the correlation coefficient(r2) was not high
      enough(0.58). When more sophisticated analytical methods are developed for
      multiple infrared data sets using a miniaturized instrument, the application of
      Fourier transform infrared analytical technique would be more advanced in the
      field of non-invasive clinical diagnosis for individuals.

PMID- 11452540
TI  - [Blood glucose measurement].
AB  - For all diabetic patients in which the blood glucose is unstable, self-monitoring
      of blood glucose (SMBG) is effective. Especially, the patient who insulin
      supplies are necessary is indispensable SMBG in spite of tyep 1 and/or type 2
      diabetes mellitus. SMBG measuring devices of looked forward nothing noninvasive
      type entered the practical stage. For example, the patient who requires the
      frequent measurement can be applied to alarms of the hypoglycemia unawareness,
      etc. from present performance, because blood glucose monitoring in the any time
      possible, though changing in taking in SMBG measuring device of the conventional
      invasive type, is not possible. And, it is possible to utilize in health care and
      protective measurement of the lifestyle related disease, etc., because the daily
      observation of the blood glucose is carried out in the long term. The function of
      data assist center, etc. is expected these this data for processing through the
      internet, etc. and follow of the result.

PMID- 11452541
TI  - [Noninvasive methods to monitor the production of hormone].
AB  - Noninvasive method to screen for endogeneous hormone production is useful to
      diagnose hormone excess/deficiency, especially in children. There are currently
      some optimal test to diagnose, and these tests(for example, urinary GH, urinary
      cortisol, urinary cathecolamine...) has been widely used. Traditional 24-hour
      urine or midnight serum cortisol values may be difficult to obtain or elevated by
      venipuncture stress. Salivary cortisol measurement has been reported as a
      reliable way to screen for adrenocortical function. We tried to detect salivary
      cortisol level with drug loading test(Dexamethasone for Cushing syndrome, and
      ACTH for adrenal insufficiency) with time interval. Salivary cortisol measurement
      with drug loading test rules out both Cushing syndrome and adrenal insufficiency
      in nearly all cases. Salivary cortisol sampling is thus a simple, accurate way to
      screen for adrenocortical function.

PMID- 11452542
TI  - [Mechanism of autoantibody production].
AB  - Autoantibody is a hallmark of autoimmune diseases. In systemic autoimmune
      diseases such as systemic lupus erythematosus, the target of autoantibodies are
      mostly nuclear autoantigens like nucleosome and U1RNP. Since immune system
      comprise autoreactivity to develop itself, the chance of autoantibody appearance
      should not be rare. Therefore, the disturbance of immunoregulation for nuclear
      autoantigens might allow the persistence of autoantibody production. The studies
      of tolerance of nuclear antigens is required to understand autoimmune diseases
      and to develop more advanced immunotherapy.

PMID- 11452543
TI  - [Anti-neutrophil cytoplasmic antibody--enzyme immunosorbent assay].
AB  - Enzyme immunosorbent assay(ELISA) is a very useful method to determine anti
      neutrophil cytoplasmic antibody(ANCA), which is an important serological marker
      for pauci-immune type systemic vasculitis and necrotizing glomerulonephritis. A
      test was made using new myeloperoxidase(MPO)-ANCA ELISA(A), employing native MPO
      purified from the neutrophils in sputum as a liquid phase antigen. Furthermore,
      the ELISA(B) using MPO, composed of one large and one small subunit, was tested
      as solid phase antigen. The intra-assay and inter-assay CV of the new ELISA(A)
      were 3.92 to 6.75% and 5.0 to 8.1%, respectively. Close ANCA titer correlation
      was shown between the new MPO-ANCA ELISA(A) and the conventional ELISA, using
      native MPO from peripheral neutrophils as solid phase antigen. ELISA(B) showed
      low MPO-ANCA detection sensitivity compared to ELISA(A) and to conventional
      ELISA. ELISA using native MPO from neutrophils in sputum as liquid phase antigen
      is useful for MPO-ANCA detection. There might be an ANCA which recognizes only
      native form MPO.

PMID- 11452544
TI  - [Present status and problem to measure autoantibodies--antinuclear antibodies].
AB  - Immunofluorescent antinuclear antibodies(FANA) technique has been widely used for
      the diagnosis of various connective tissue diseases for more than forty years.
      The frequency of FANA in healthy individuals, however, has elevated by recent
      technical advance using HEp-2 cell. In addition, clinical significance to
      differentiate immunofluorescent staining patterns also reduced since it has been
      possible to measure individual antinuclear antibodies specific for a variety of
      connective tissue diseases. Instead of FANA technique, enzyme-linked
      immunosorbent assay coated with a mixture of disease specific antinuclear
      antigens seems to be a new approach to screen antinuclear antibodies that will
      increase the specificity for connective tissue diseases.

PMID- 11452545
TI  - [Rheumatoid factor].
AB  - To know the present situation of rheumatoid factor(RF) measurements, the
      questionnaire was sent to 82 University or College hospitals in Japan and
      regional 133 hospitals in Fukushima prefecture. Evaluation of qualitative RF kits
      commercially purchased in Japan was also performed. In RF measurement,
      quantitative methods have been increasingly used compared with semiquantitative
      or qualitative methods. Among quantitative RF measurement methods, latex
      immunoassay including latex-turbidimetry and latex-nephelometry is most
      frequently used. The reference values of RF distributed widely ranging from 5 to
      40 unit. The 1997 JMA survey still showed interlaboratory differences in
      quantitative RF measurement. Qualitative RF kits were also shown to have variety
      of reactivities. To promote the improvement of current situation in RF
      measurement, "arbitrary" reference materials should be established urgently.

PMID- 11452546
TI  - [Pathologists and laboratory medicine: personal experiences].
AB  - The author started his career as an anatomical pathologist and now works as an
      anatomical and clinical pathologist. Most Japanese anatomical pathologists are
      not well trained for laboratory medicine, but they are required to have a
      knowledge of laboratory medicine and are expected to become managers of
      laboratories in general hospitals. The reconstruction of the laboratory is
      necessary to include an anatomical pathology division and a new post-graduate
      education system should be established in which both anatomical and clinical
      pathologists should be cross-taught mutual fields.

PMID- 11452547
TI  - [Present status and future problems of clinical laboratory from view points of an
      anatomical pathologist].
AB  - The medical situation surrounding laboratory examinations has changed remarkably.
      We, the staff of laboratory divisions, must offer the best medical care for
      patients and operate efficiently. Fertility management service(FMS) and branch
      laboratory(Branch Lab.) are examples of useful contributions to our hospital from
      the perspective of economy and personnel expenditure including staff attrition.

PMID- 11452548
TI  - [Challenges for pathologists in clinical laboratory medicine].
AB  - The number of pathologists in hospitals has been increasing and they are
      responsible for both surgical pathology and clinical laboratory medicine. In the
      future they will also play important roles in the modernized reform of the
      central laboratory as it establishes its own importance in improving the quality
      and safety of medical activities. As a pathologist, the author reports on
      challenges faced since assuming the present directorship of the department of
      laboratory medicine in 1995 including (a) establishing a decision-making system
      in collaboration with technologists, (b) improving expertise in the department
      through joining a variety of seminars, conferences and research activities, (c)
      publishing an annual department report, and (d) introducing both internal and
      external quality assessment. In the future, for young pathologists training in
      both pathology and laboratory medicine will be essential.

PMID- 11452549
TI  - [The relationship of serum mitochondrial creatine kinase and rotavirus
      gastroenteritis in pediatric patients].
AB  - The objective of this study was to investigate the relationship between serum
      mitochondrial creatine kinase(mCK) and rotavirus gastroenteritis in pediatric
      patients. Stool and serum specimens were simultaneously collected from 45
      patients(25 males and 20 females) with suspected rotavirus gastroenteritis from
      January to December 1998. Stool specimens were tested by rotavirus latex
      agglutination assay. Fourteen patients(10 males, 4 females) were proved as
      positive, and peak season was in winter and early spring(7 positive cases in
      March). Six of the 14 were younger than one and 7 were between one and two. Total
      serum CK activity was measured by The Japan Society of Clinical Chemistry (JSCC)
      recommended method, and mCK activity was calculated from mCK fraction % obtained
      by CK isoenzyme electrophoresis. Patients' mCK activities were as follows,
      rotavirus antigen positive patients(n = 14): 60.0 +/- 20.6 U/l and rotavirus
      antigen negative patients(n = 31): 7.2 +/- 5.5 U/l. Significant difference was
      observed between rotavirus antigen positive group and rotavirus antigen negative
      group(p < 0.01), and control children group(n = 105): 7.1 +/- 2.9 U/l, (p <
      0.01). The clinical implications and mechanisms of increased serum mCK activity
      are unclear. It is known that histological study of the small intestine from
      rotavirus gastroenteritis patients reveal shortened villi and mononuclear cell
      infiltration of the lamia propria; electron microscopy shows mitochondrial
      swelling and sparse irregular microvilli. Elevated serum mCK level of rotavirus
      gastroenteritis patient may therefore reflect diffused intestinal epithelial cell
      damage.

PMID- 11452550
TI  - [Development and preliminary analysis for EBV clonality using non-RI probe].
AB  - We develop a method for EBV clonality analysis by southern blot hybridization
      using Non-RI probes directed to EBV genome. We also tried to use newly developed
      method for several cells, which have been known as EBV genome carrier, and for a
      clinically diagnosed specimen from patients of infectious mononucleosis (IM) and
      chronic active EBV infection(CAEBV). Non-RI probe(directed to terminal repeat of
      EBV genome, TR probe) were made by following ways; The Xho I fragment(1.9 Kb) of
      B95-8 cells(carrier of EBV genome) was amplified by PCR, and the product was
      cloned into pBluescript, and cloned DNA were labeled by digoxigenin(Dig) after
      purification. The TR probes did not hybridize with DNA from other herpes viruses
      and Ramos cells(EBV-free cell line). When TR probe used against peripheral blood
      mononuclear cells(PBMCs) from a CAEBV patient, pattern was monoclonal as same as
      the case of Raji cells. In the case of B95-8 cells and PBMCs of IM patient,
      patterns were polyclonal. These results were the same as those of previously
      reported. This method was possible to detect about 0.3% target Raji's DNA from
      the mixture of Raji and Ramos cells. Above results indicated that this newly
      developed method was considered to be superior method in specificity and
      sensitivity, and also suggested that it was useful for analyzing the clonality of
      EBV infected cells in daily clinical examinations without radiological equipment
      and facilities.

PMID- 11452551
TI  - [Significance of nucleic acid extraction for the performance of COBAS AMPLICOR
      Mycobacterium-PCR assay].
AB  - On an AMPLICOR-PCR assay for the diagnosis of mycobacterial infections, it has
      been found that approximately 10% of the routinely performed assays appear as
      indefinable cases with internal control (IC)-negative, which is caused by
      contaminant PCR-inhibitory substances in the extracted nucleic sample. To
      decrease the number of indefinable cases, we studied the IC performance of four
      nucleic acid extraction methods in one manual method(A) and three commercial
      kits(B, C and D). Thirty samples from 10 kinds of specimens without mycobacterial
      infections were subjected to the four nucleic extraction methods and the nucleic
      extracts were compared on PCR-inhibitory. The frequency of IC-negative samples
      was different among the four methods and the rates were 33.3%(n = 10) in A,
      30.0%(n = 9) in B, 16.7%(n = 5) in C and 6.7%(n = 2) in D. In the PCR-inhibitory
      experiments using serially diluted IC-negative samples, the recovery of IC
      positivity was also different according to the method used. Although the IC
      negative nucleic samples by D method easily became IC-positive at the 1/5 range
      of dilution, some of the IC-negative nucleic samples by A, B or C method were
      still IC-negative in the 1/10 range. These results indicate that the occurrence
      rate of indefinable cases with IC-negative is markedly different in the nucleic
      extraction method, suggesting that utilizing a suitable nucleic acid extraction
      method is important when using the diagnostic AMPLICOR-PCR assay.

PMID- 11452552
TI  - A scoring system for ultrasonographic differentiation between cervical malignant
      lymphoma and benign lymphadenitis.
AB  - The purpose of our study is to assess the usefulness of a scoring system for
      ultrasonography using a high-frequency transducer as a non-invasive examination
      in the differential diagnosis of cervical malignant lymphoma from benign
      lymphadenitis. Ultrasonography was performed with a real-time linear scanner
      using 7.5 and/or 11 MHz probes in 66 patients who were presented with cervical
      lymphadenopathy and were suspected to have malignant lymphoma. Thereafter, a
      surgical biopsy was performed for histopathological diagnosis, revealing 49 cases
      of malignant lymphoma and 17 cases of benign lymphadenitis. Ultrasonographic
      findings were reviewed retrospectively. The incidence of following
      ultrasonographic features was found to be significantly higher in malignant
      lymphoma than in benign lymphadenitis. These were; (1) longitudinal and
      transverse diameter ratio(L/T) < 2.0, (2) a delineation of multiple nodes, (3) a
      tendency of fusion, (4) an irregular margin, (5) hypoechoic masses with
      heterogeneous internal echoes, (6) a presence of line echoes and (7) an absence
      of hilum. These 7 ultrasonographic features were used in combination for a
      scoring system to discriminate malignant lymphoma from benign lymphadenitis. When
      ultrasonographic findings of lymph nodes fulfilled more than 3 of the 7 features,
      malignant lymphoma was diagnosed with a sensitivity of 98.0% and a specificity of
      76.5%. Ultrasonographic evaluation of swollen cervical lymph nodes using a high
      frequency transducer would be informative and should be performed prior to a
      surgical biopsy.

PMID- 11452553
TI  - Progress notes: University of North Carolina, Chapel Hill.

PMID- 11452554
TI  - Looking within: urban ethnomedicine and ethnobotany.

PMID- 11452555
TI  - In praise of toilets.

PMID- 11452556
TI  - Haelth: Building the bridge and keeping it open.

PMID- 11452557
TI  - Integrating complementary and alternative medicine with allopathic care in the
      neonatal intensive care unit .

PMID- 11452558
TI  - Where are cancer survivors in the Iscador study?

PMID- 11452559
TI  - Meditation defined unsatisfactorily in article.

PMID- 11452560
TI  - Clinical pharmacist talks to plants, too.

PMID- 11452561
TI  - Author of CME article offers clarification about Essiac.

PMID- 11452562
TI  - On breasts and beyond.

PMID- 11452563
TI  - Surfing the odornet: a reflective response.

PMID- 11452564
TI  - The medium is not the message: a carrier and signal hypothesis.

PMID- 11452565
TI  - What we do, what we should do, and what we should not do.

PMID- 11452566
TI  - Maximizing the effectiveness of acupuncture: prospects from clinical studies.

PMID- 11452567
TI  - An integrative approach to menopause.

PMID- 11452568
TI  - Clinical decisions in the use of acupuncture as an adjunctive therapy for
      osteoarthritis of the knee.
AB  - OBJECTIVE: To determine whether demographic, medical history, or arthritis
      assessment data may influence outcome and rate of decay for patients with
      osteoarthritis treated with acupuncture. DESIGN: Seventy-three persons with
      symptomatic osteoarthritis of the knee were recruited for this randomized
      controlled trial. Both treatment and crossover control groups received
      acupuncture treatments twice weekly for 8 weeks. Patients self-scored on the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the
      Lequesne Algofunctional Index at baseline and 4, 8, and 12 weeks. Sample size for
      this outcome analysis was 60 patients at 4 weeks, 58 at 8 weeks, and 52 at 12
      weeks. RESULTS: Patients' scores on both indexes improved at 4, 8, and 12 weeks.
      Scores were stable regardless of the baseline severity of the osteoarthritis.
      Despite some decay in outcomes at week 12, measures were significantly improved
      over baseline. With WOMAC scores partitioned into equal quartiles, a strong
      effect on outcome was apparent at 12 weeks (4 weeks after treatment) related to
      initial WOMAC scores. The group with the least disability and pain rebounded to
      original levels to a greater degree than did those who initially were more
      disabled. The more disabled groups retained the benefits of acupuncture treatment
      through the 12-week period. CONCLUSION: Acupuncture for patients with
      osteoarthritis of the knee may best be used early in the treatment plan, with a
      methodical decrease in frequency in treatment once the acute treatment period is
      completed to avoid a rebound effect. Demographic and medical history data were
      not mediating variables.

PMID- 11452569
TI  - Utilization, patient satisfaction, and cost implications of acupuncture, massage,
      and naturopathic medicine offered as covered health benefits: a comparison of two
      delivery models.
AB  - CONTEXT: Increasing numbers of health plans in the United States offer
      complementary and alternative medicine (CAM) benefits despite limited
      information. OBJECTIVE: To determine the utilization rates and costs associated
      with providing CAM services in 2 benefit designs, and to determine the
      satisfaction of patients in both plans. DESIGN: Two health plans were identified:
      a traditional indemnity plan offered through a defined preferred provider
      organization (PPO) of CAM providers and a health maintenance organization (HMO).
      Costs and utilization rates for CAM services were compared during a 1-year period
      of coverage beginning November 1, 1996. SETTING AND PARTICIPANTS: 1091 patients
      in both plans who used CAM services during the month of May 1997 in Washington
      state. RESULTS: Only 1% of all patients covered for CAM accessed these services
      during the study period. A significantly higher percentage of patients in the PPO
      plan (1.2%) used CAM services compared to the HMO plan (0.6%) (P < .001).
      However, the average total cost of annual CAM services (plan benefit + user
      contribution) was similar ($347 in the HMO and $376 in the PPO), and the price
      per member per month was nearly identical ($0.20 in the HMO and $0.19 in the
      PPO). Most users perceived these services as helpful. CONCLUSIONS: Utilization of
      CAM services and per member per month costs were lower than expected given the
      high interest in CAM services reported in consumer surveys. The high level of
      satisfaction with CAM services and self-reported decrease in the use of pain
      medications suggests the need for prospective studies examining the effect of CAM
      treatments.

PMID- 11452570
TI  - Oriental medicine: an introduction.
AB  - This article covers introductory concepts regarding Oriental medicine, its
      historical context, yin and yang principles, and Five-Phase theory. It discusses
      organ theory, patient examination, diagnosis, the meridian network system, and
      treatment modalities such as acupuncture and Chinese herbal medicine, giving a
      brief overview of the different acupuncture and Oriental medical styles practiced
      in the United States. Included also are helpful tables, graphs, and photographs
      to provide a better visual context for Oriental medicine.

PMID- 11452571
TI  - Designing clinical trials on energy healing: ancient art encounters medical
      science.
AB  - Demand for energy healing is growing rapidly in the United States. Until
      recently, however, few clinical trials have been conducted to investigate its
      clinical efficacy, risks, and cost-effectiveness. This article discusses
      principles underlying the research design of clinical trials on energy healing,
      based on the experience of an interdisciplinary team conducting a large-sample
      clinical study on qigong funded by the National Institutes of Health. The first
      part overviews the background and contemporary practice of qigong therapy. The
      second addresses some difficulties and unique issues to be considered in
      designing a clinical trial on energy healing. These issues include research
      emphasis on outcome versus mechanism, randomization, control,
      expectations/placebo effects, staff and practitioner bias/conflict of interest,
      patients' belief, selection bias, intent-to-treat analysis, ethics, informed
      consent, sample size, and outcome report. The ultimate goal is to promote more
      scholarly and clinical discussion on the evaluation of energy healing.

PMID- 11452572
TI  - Acupressure relieves the symptoms of motion sickness and reduces abnormal gastric
      activity.
AB  - CONTEXT: Acupuncture at the P6 or Neiguan point to treat nausea and vomiting has
      been practiced in China for many years. More recently, acupressure at P6 has been
      used successfully to decrease the symptoms of pregnancy sickness and with mixed
      results to decrease motion sickness. OBJECTIVE: To determine whether an Acuband,
      a commercially available acupressure wristband, would relieve the symptoms of
      motion sickness. METHOD: 25 healthy subjects, aged 18 to 22 years, prescreened
      for susceptibility to motion sickness, were tested on 3 separate occasions in a
      rotating optokinetic drum with the following conditions: wearing an Acuband on
      the wrist, wearing an Acuband on the arm, and wearing no Acuband. MAIN OUTCOME
      MEASURES: Subjective symptoms of motion sickness and abnormal gastric activity,
      as recorded via electrogastrography, were obtained throughout the procedure.
      RESULTS: Subjects reported significantly fewer symptoms of motion sickness on
      days when wearing the Acuband on the wrist or the arm than they did on control
      days (when they wore no Acuband). Subjects also showed less abnormal gastric
      activity on the days when wearing an Acuband than they did on control days.
      CONCLUSION: An Acuband worn on the wrist or forearm decreases the symptoms of
      motion sickness and the gastric activity that usually accompanies motion
      sickness.

PMID- 11452573
TI  - Life cycle of a data warehousing project in healthcare.
AB  - Hill Physicians Medical Group (and its medical management firm, PriMed
      Management) early on recognized the need for a data warehouse. Management
      demanded that data from many sources be integrated, cleansed, and formatted. As a
      first step, an operational data store (ODS) was built and populated with data
      from the main transactional system; encounter data were added. The ODS has served
      its purpose well and has whetted management's appetite for more information and
      faster, more reliable access, all in one location. PriMed hired Annams Systems
      Consulting (Annams) for this effort. A team was formed, made up of consultants
      from Annams and members of PriMed's information services (IS) team. The
      "classical" approach is being taken: enhancing the ODS, which is largely
      normalized in structure, and integrating data from various sources, along with
      enforcing business rules. The team is designing and implementing data marts and a
      "star schema" style of data modeling--a useful tool for management to evaluate
      results before investing further.

PMID- 11452574
TI  - Toward best practice: leveraging the electronic patient record as a clinical data
      warehouse.
AB  - Automating clinical and administrative processes via an electronic patient record
      (EPR) gives clinicians the point-of-care tools they need to deliver better
      patient care. However, to improve clinical practice as a whole and then evaluate
      it, healthcare must go beyond basic automation and convert EPR data into
      aggregated, multidimensional information. Unfortunately, few EPR systems have the
      established, powerful analytical clinical data warehouses (CDWs) required for
      this conversion. This article describes how an organization can support best
      practice by leveraging a CDW that is fully integrated into its EPR and clinical
      decision support (CDS) system. The article (1) discusses the requirements for
      comprehensive CDS, including on-line analytical processing (OLAP) of data at both
      transactional and aggregate levels, (2) suggests that the transactional data
      acquired by an OLTP EPR system must be remodeled to support retrospective,
      population-based, aggregate analysis of those data, and (3) concludes that this
      aggregate analysis is best provided by a separate CDW system.

PMID- 11452575
TI  - Interactively visualizing data warehouses.
AB  - As healthcare costs continue to rise, along with the urgency to control these
      costs, timely analyses of operational data stored in data warehouses have become
      critical. Although healthcare organizations have begun to amass large volumes of
      raw data within data warehouses, many have yet to capitalize on that valuable
      information. Many clinical and financial events are recorded each day, yet few of
      these data are leveraged to increase organizational awareness and performance.
      Because the development and implementation of a data warehouse requires
      significant time and capital, as well as highly skilled labor, the need to more
      fully leverage this considerable investment demands techniques that facilitate
      detailed data exploration, analysis, and the subsequent communication of
      findings. This article describes how the effective display of complex
      relationships in data can be used to discover areas of variance in large,
      changing data warehouses.

PMID- 11452576
TI  - A data mart for operations analysis.
AB  - In this article we describe the evolution and architecture of a data mart
      developed to address the modeling and analysis needs of healthcare operations
      analysts. More specifically, the data mart is used in projects relating to demand
      analysis, forecasting, capacity planning, and service system design for a
      healthcare system consisting of a large tertiary care hospital and a smaller
      community hospital. The primary focus of the mart is on the detailed movement of
      inpatients through each hospital, although most component data tables include
      outpatient information such as emergency center visits, surgical cases, cardiac
      catheterization cases, and short-stay visits. We show that the data mart goes
      well beyond consolidating data from different sources by including a number of
      complex, precalculated fields, data structures, and function libraries that are
      specific to the needs of operations analysts. We discuss several outstanding and
      challenging design issues that should be of interest to the data warehouse vendor
      community.

PMID- 11452577
TI  - Case study: how to apply data mining techniques in a healthcare data warehouse.
AB  - Healthcare provider organizations are faced with a rising number of financial
      pressures. Both administrators and physicians need help analyzing large numbers
      of clinical and financial data when making decisions. To assist them, Rush
      Presbyterian-St. Luke's Medical Center and Hitachi America, Ltd. (HAL), Inc.,
      have partnered to build an enterprise data warehouse and perform a series of case
      study analyses. This article focuses on one analysis, which was performed by a
      team of physicians and computer science researchers, using a commercially
      available on-line analytical processing (OLAP) tool in conjunction with
      proprietary data mining techniques developed by HAL researchers. The initial
      objective of the analysis was to discover how to use data mining techniques to
      make business decisions that can influence cost, revenue, and operational
      efficiency while maintaining a high level of care. Another objective was to
      understand how to apply these techniques appropriately and to find a repeatable
      method for analyzing data and finding business insights. The process used to
      identify opportunities and effect changes is described.

PMID- 11452578
TI  - Case study: a data warehouse for an academic medical center.
AB  - The clinical data repository (CDR) is a frequently updated relational data
      warehouse that provides users with direct access to detailed, flexible, and rapid
      retrospective views of clinical, administrative, and financial patient data for
      the University of Virginia Health System. This article presents a case study of
      the CDR, detailing its five-year history and focusing on the unique role of data
      warehousing in an academic medical center. Specifically, the CDR must support
      multiple missions, including research and education, in addition to
      administration and management. Users include not only analysts and administrators
      but clinicians, researchers, and students.

PMID- 11452579
TI  - Successful database benchmarking: what do we need?
AB  - As the technology of on-line healthcare information advances, hospitals and data
      vendors are faced with a variety of challenges. What are the accepted standard
      fields? What kind of DSS system should we use? Which system will give us the
      information we need? Does the server have enough space to handle increased
      business? Healthcare organizations are now looking at comparative information
      through the Internet instead of buying data and loading it onto their own
      servers. They are asking: Are servers necessary now? Is the software user
      friendly? How current and accurate is the information being offered? How secure
      is the Web site it is on? Data vendors are asking: Is our server large enough to
      handle the volume of data we now have and as the company grows? How do we make
      sure the data are accurate? How do we keep the data secure? This article educates
      and informs healthcare facilities about the factors that should be considered
      when comparing their own data with those of other hospitals in an on-line
      benchmarking database warehouse.

PMID- 11452580
TI  - Challenges faced by e-healthcare comparative data warehouses.
AB  - More and more healthcare facilities are equipping themselves with DSS systems and
      looking at their own data in a benchmarking manner. Some are considering
      accessing data from other healthcare facilities to decrease costs while improving
      quality of care. Many vendors claim to have that information. Some redistribute
      publicly available data; others actively seek information from a multitude of
      facilities. Those vendors are faced with many challenges as they try to provide
      information that is meaningful and usable for their clients. This article
      explores some of these challenges, particularly the data and technical
      challenges. It addresses the issues of standardizing data, as well as the
      technology to manage and secure that information, and provides examples that
      illustrate solutions that some vendors have implemented.

PMID- 11452581
TI  - Implementing a data warehouse at Inglis Innovative Services.
AB  - Data warehouses, data marts, and data mining have been hot topics in the 1990s,
      offering the promise of a vault of corporate data ripe for decision making. As is
      true with all promising technologies, the key issue is how to get started.
      Implementation of a corporate data warehouse involves a lot more than spending a
      huge amount of money on hardware, software, and consultants. Successful
      implementation of a data warehouse involves a corporate treasure hunt-
      identifying and cataloging data. It involves data ownership, data integrity, and
      business process analysis to determine what the data are, who owns them, how
      reliable they are, and how they are processed. Finally, implementation of the
      warehouse drives the issue of how good the decisions are that are based on the
      information in the warehouse. This article presents a case study of how one
      healthcare facility dealt with the challenges of implementing a data warehouse.

PMID- 11452582
TI  - Data warehousing in disease management programs.
AB  - Disease management programs offer the benefits of lower disease occurrence,
      improved patient care, and lower healthcare costs. In such programs, the key
      mechanism used to identify individuals at risk for targeted diseases is the data
      warehouse. This article surveys recent warehousing techniques from HMOs to map
      out critical issues relating to the preparation, design, and implementation of a
      successful data warehouse. Discussions of scope, data cleansing, and storage
      management are included in depicting warehouse preparation and design; data
      implementation options are contrasted. Examples are provided of data warehouse
      execution in disease management programs that identify members with preexisting
      illnesses, as well as those exhibiting high-risk conditions. The proper
      deployment of successful data warehouses in disease management programs benefits
      both the organization and the member. Organizations benefit from decreased
      medical costs; members benefit through an improved quality of life through
      disease-specific care.

PMID- 11452583
TI  - Arsenic contamination of groundwater and drinking water in Vietnam: a human
      health threat.
AB  - This is the first publication on arsenic contamination of the Red River alluvial
      tract in the city of Hanoi and in the surrounding rural districts. Due to
      naturally occurring organic matter in the sediments, the groundwaters are anoxic
      and rich in iron. With an average arsenic concentration of 159 micrograms/L, the
      contamination levels varied from 1 to 3050 micrograms/L in rural groundwater
      samples from private small-scale tubewells. In a highly affected rural area, the
      groundwater used directly as drinking water had an average concentration of 430
      micrograms/L. Analysis of raw groundwater pumped from the lower aquifer for the
      Hanoi water supply yielded arsenic levels of 240-320 micrograms/L in three of
      eight treatment plants and 37-82 micrograms/L in another five plants. Aeration
      and sand filtration that are applied in the treatment plants for iron removal
      lowered the arsenic concentrations to levels of 25-91 micrograms/L, but 50%
      remained above the Vietnamese Standard of 50 micrograms/L. Extracts of sediment
      samples from five bore cores showed a correlation of arsenic and iron contents
      (r2 = 0.700, n = 64). The arsenic in the sediments may be associated with iron
      oxyhydroxides and released to the groundwater by reductive dissolution of iron.
      Oxidation of sulfide phases could also release arsenic to the groundwater, but
      sulfur concentrations in sediments were below 1 mg/g. The high arsenic
      concentrations found in the tubewells (48% above 50 micrograms/L and 20% above
      150 micrograms/L) indicate that several million people consuming untreated
      groundwater might be at a considerable risk of chronic arsenic poisoning.

PMID- 11452584
TI  - Speciation of mercury in a fluid mud profile of a highly turbid macrotidal
      estuary (Gironde, France).
AB  - Mercury (Hg) speciation and partitioning have been investigated in a fluid mud
      profile collected in the high turbidity zone of the Gironde estuary. The
      formation of the fluid lens generates local and transient oxic-anoxic
      oscillations following the sedimentation-resuspension tidal cycles under a
      specific hydrodynamic regime. The total Hg concentration, ranging from 5 to 190
      nM, increases with SPM concentration (4-174 g L-1) to a maximum at bottom.
      Particulate Hg averages 99% of total Hg. Particulate inorganic Hg (IHg(II)P) and
      monomethyl Hg (MMHgP) exhibit a similar trend: the maximum concentration is
      observed within the upper layer above the depth of 7 m and the minimum at the
      bottom layers of the fluid mud. Significant levels of "dissolved" (i.e. filter
      passing) Hg species (IHg(II)D, HgoD, MMHgD, DMHgD) are observed within the redox
      transition interface. In the sub/anoxic fluid mud layer, increasing
      concentrations of IHg(II)D and MMHgD coincide with decreasing concentrations of
      IHg(II)P and MMHgP, respectively. The distribution coefficient (log Kd) between
      the "dissolved" and particulate fraction for IHg(II) averages 4.5 +/- 0.2. A Kd
      minimum for IHg(II) is observed in the surface layer and at the bottom of the
      fluid mud and coincides with the maximum levels of dissolved Mn and Fe. Log Kd
      for MMHg averages 3.3 +/- 0.9 and presents the highest values (4.3-4.6) in the
      surface and the lowest (approximately 2.2) at bottom, corresponding to the
      particulate carbon profile. These results demonstrate that the fate of IHg(II)
      and MMHg in the fluid mud system is influenced by the redox cycling of major
      species such as carbon, Fe, and Mn. It is therefore suggested that the redox
      oscillations generated by fluid mud formation in the high turbidity zone affect
      the distribution and transfer of Hg species in macrotidal estuaries.

PMID- 11452585
TI  - Accumulation and decay of chlorothalonil and selected metabolites in surface soil
      following foliar application to peanuts.
AB  - One of the principal uses of the fungicide, chlorothalonil, is control of foliar
      peanut diseases. Recent assessments indicate its runoff from treated fields in
      southeastern states presents risks to aquatic life. Two factors that control its
      runoff are how much reaches soil surfaces and degradation rates. To address these
      questions and to evaluate accumulation and decay of key metabolites, soil samples
      (0-2 cm) were collected after seven chlorothalonil applications on experimental
      peanut plots in south central Georgia during the 1999 growing season. At the
      start of and during laboratory incubations, samples were analyzed for the parent
      and degradates by HPLC-PDA-APCI-MS. The maximum observed residue levels were
      after the second application, after which canopy closure reduced soil deposition
      from later applications to 5-10% of applied amounts. After the last spray, < 5%
      of the cumulative chlorothalonil applied was detected in the soil. Foliar
      interception and dissipation and rapid soil degradation contributed to low
      residue levels. Soil half-lives were < 1-3.5 days for chlorothalonil and 10-22
      days for its principal degradate, 4-hydroxychlorothalonil. Other daughter and
      granddaughter products were detected, some of which accumulated during the
      growing season. Results emphasize the plant canopy role in controlling the amount
      of fungicide sprays that reach soil surfaces and suggest concentration-dependent
      chlorothalonil degradation with degradation rates increasing as soil loading
      decreases. The study indicates that the 30-day field half-life often used for
      risk assessments of this pesticide is too long for one of its most important
      agronomic uses, i.e., in southeastern peanut production. It also indicates that
      the principal metabolites are more persistent than the parent, and more study is
      needed to identify and quantify their fate pathways.

PMID- 11452586
TI  - Aromatic hydrocarbon "humps" in the marine environment: unrecognized toxins?
AB  - Gas chromatographic analysis of the hydrocarbons of environmental samples often
      reveals that unresolved complex mixtures (UCMs) or gas chromatographic "humps" of
      aliphatic and aromatic hydrocarbons are most abundant--yet little consideration
      seems to have been given to the possible toxicological impacts of hydrocarbon
      "humps". Here we show, using a well-accepted bioassay, that monoaromatic
      components of a UCM of hydrocarbons from a crude oil elicit a sublethal toxic
      response in a typical marine pollution indicator organism (the mussel, Mytilus
      edulis). Furthermore, coastal U.K. mussels shown previously to have unexplained
      impaired health contained high concentrations of UCMs, including monoaromatic
      UCMs. These findings may have important implications for our understanding of the
      toxicological sublethal effects of oil residues in the environment. Given the
      relatively resistant nature of UCM hydrocarbons, the effects of both acute oil
      spills and more chronic discharges may need further consideration.

PMID- 11452587
TI  - Benzo(a)pyrene, benzo(a)anthracene, and dibenzo(a,h)anthracene emissions from
      coal and waste tire energy generation at atmospheric fluidized bed combustion
      (AFBC).
AB  - The main aim of this work was the analyzing of the release to the atmosphere of
      benzo[a]pyrene (BaP), dibenzo(a,h)anthracene (D(a,h)A), and benzo[a]anthracene
      (BaA), three of the most carcinogenic PAHs listed by US-EPA as priority
      pollutants, emitted from combustion at the last generation reactors used nowadays
      in power generation, fluidized bed reactors, trying to establish their incidence
      when waste materials are used as "new fuels". BaP, D(a,h)A, and BaA emissions,
      once collected in the sampling system, have been analyzed by fluorescence
      spectroscopy in the synchronous mode (FS) after extraction by ultrasonic bath
      with dimethylformamide (DMF) as solvent. Concerning to the combustion variables
      influence, the conclusion reached was that, in coal combustion, the lowest
      emissions of BaP are generated at percentages of excess oxygen of 20%, at flows
      corresponding to good fluidization conditions, 860 L/h (double of the minimum
      fluidization velocity) and temperatures out of 850 degrees C; the lowest emission
      of D(a,h)A are emitted at 20% excess oxygen, 900 L/h and out of 750 degrees C,
      and the lowest emission of BaA are generated at 20% excess oxygen, 860 L/h and
      out of the range 750-850 degrees C. Regarding tire as nonfossil fuel, higher
      emissions of BaP, BaA, and D(a,h)A are detected in comparison to coal combustion.
      In coal-tire blend, the BaP, BaA, and D(a,h)A emissions are more similar to the
      values obtained in coal combustion and not intermediate values as it could be
      expected by the blend composition.

PMID- 11452588
TI  - Indoor respirable particulate matter concentrations from an open fire, improved
      cookstove, and LPG/open fire combination in a rural Guatemalan community.
AB  - Improved biomass cookstoves have the potential to reduce pollutant emissions and
      thereby reduce pollution exposure among populations in developing countries who
      cook daily with biomass fuels. However, evaluation of such interventions has been
      very limited. This article presents results from a study carried out in 30
      households in rural Guatemala. Twenty-four hour PM3.5 concentrations were
      compared over 8 months for three fuel/cookstove conditions (n = 10 households for
      each condition): a traditional open fire cookstove, an improved cookstove called
      the plancha mejorada, and a liquefied petroleum gas (LPG) stove/open fire
      combination. Twenty-four hour geometric mean PM3.5 concentrations were 1560
      micrograms/m3 (n = 58; 95% C.I. 1310, 1850), 280 micrograms/m3 (n = 59; 95% C.I.
      240-320), and 850 micrograms/m3 (n = 60; 95% C.I. 680-1050) for the open fire,
      plancha, and LPG/open fire combination, respectively. A generalized estimating
      equation model showed a 45% reduction in PM3.5 concentrations for the LPG/open
      fire combination as compared to the open fire alone. The difference approached
      significance (p < 0.0737). The plancha showed an 85% reduction in PM3.5
      concentrations as compared to the open fire (p < 0.0001). An analysis of the
      interaction of time with stove type showed that the temporal trend in pollution
      did not significantly differ among the three stove types. The reduced PM3.5
      concentrations were maintained over time. Season did not affect pollutant
      concentrations. Of the two interventions, the plancha appears to offer the best
      prospects for achieving substantial reductions in indoor air pollution levels,
      although issues of cost and stove maintenance remain to be addressed.

PMID- 11452589
TI  - 1H NMR application for characterizing water-soluble organic compounds in urban
      atmospheric particles.
AB  - Water-soluble organic compounds (WSOC) in urban atmospheric particles separated
      by particle size were analyzed by 1H NMR. This is the first utilization of 1H NMR
      for characterizing WSOC in atmospheric particles. The WSOC dissolved in D2O were
      analyzed without a separation procedure. Twelve low molecular weight WSOC could
      be identified and their atmospheric concentrations determined. One of these,
      monomethyl hydrogen sulfate (MHS), was first detected in an urban area where no
      oil or coal power plant existed. Methanesulfonic acid (MSA) and
      hydroxymethanesulfonic acid (HMSA) were detected as major organosulfur compounds.
      Relatively high concentrations of these low molecular weight WSOC were observed
      in the particle diameter range of 0.43-1.1 microns. Many complex signals at 3-4
      ppm in the NMR spectrum were seen only for the coarse particle samples (1.1
      microns < particle diameter). Mannitol was believed to exist in the coarse
      particles as a major polyol corresponding to these signals. On the other hand, a
      large broad signal, observed at 2.5-3 ppm, was mostly present in the fine
      particles. Finally, it was believed that a major part of the WSOC in urban
      atmospheric fine particles is attributed to ketocarboxylic acids,
      ketodicarboxylic acids, and dicarboxylic acids.

PMID- 11452590
TI  - Chemical characterization of fine particle emissions from fireplace combustion of
      woods grown in the northeastern United States.
AB  - A series of source tests was conducted to determine the chemical composition of
      fine particle emissions from the fireplace combustion of six species of woods
      grown in the northeastern United States: red maple, northern red oak, paper
      birch, eastern white pine, eastern hemlock, and balsam fir. Results include fine
      particle emission rates for total mass, organic and elemental carbon, ionic
      species, elemental species including potassium, and over 250 specific organic
      compounds. The data are intended for use in source-apportionment studies that
      utilize particulate organic compounds as source-specific tracers. The cellulose
      pyrolysis product levoglucosan was quantified in each of the wood smokes studied
      and is thus a good candidate as a molecular tracer for wood combustion in
      general. Differences in emission rates of specific substituted phenols and resin
      acids can be used to distinguish between the smoke produced when burning
      hardwoods versus softwoods. Certain organic compounds, such as betulin from paper
      birch combustion and juvabione and dehydrojuvabione from balsam fir combustion,
      are unique to those species and can potentially be utilized to trace particulate
      emissions back to a specific geographical region where those individual tree
      species are used for firewood.

PMID- 11452591
TI  - Multivariate analysis of U.K. salt marsh sediment contaminant data with reference
      to the significance of PCB contamination.
AB  - A data set acquired to establish an inventory of pollutants in salt marsh
      sediments has been evaluated using two numerical techniques, principal component
      analysis and discriminant analysis. Results indicate that sites proximate to the
      River Thames exhibit a greater degree of contamination, and numerical analysis
      supports the hypothesis that the river has been the major source of contaminants
      to the region. The presence of the contaminants within salt marsh sediments may
      be of concern due to changes in flood defense techniques. The use of managed
      realignment, where the line of flood defense is moved back to higher ground which
      requires only a low, minimal cost, sea-wall protected by newly created salt marsh
      from former farmland, is not free from problems of historical pollution. Mature
      salt marsh, laid down during previous decades, may be eroded and reworked within
      the new coastal geomorphology created by breaching existing seawalls and what
      were previously considered to be sinks of pollutants may have become sources.
      However, evaluation of the sediment burden of PCB within the salt marshes of the
      U.K. Essex coast indicates that they are not likely to be a major source of
      pollutants should sediments be remobilized during managed realignment programs.

PMID- 11452592
TI  - A potential source of organic pollutants into the northeastern Atlantic: the
      outflow of the Mediterranean deep-lying waters through the Gibraltar Strait.
AB  - Small and large-size particles were collected in the water column (50-3000 m) of
      a Northeastern Atlantic area where deep Mediterranean waters, outflowing through
      the Strait of Gibraltar, are incorporated at mid-depth. Particles collected by
      water filtration (0.7 micron pore size) and by vertical hauls of a neuston net
      (50 microns mesh size) were analyzed for organic pollutants, namely aliphatic and
      aromatic hydrocarbons, and organochlorine compounds. Small-size particles
      represented the largest bulk of particulate organic carbon as well as of
      hydrophobic organic pollutants. Surface concentrations of n-alkanes [C14-C35),
      aromatic hydrocarbons (12 parent compounds), PCBs (7 congeners), and DDTs (DDT +
      DDE) were, respectively, in the range of 50-63 ng/L, 23-68 pg/L, 8-13 pg/L, and
      0.05-1.7 pg/L. These concentrations showed a general decrease with depth,
      particularly significant in the upper 200 m, consistently with the POC contents.
      Compositional changes with depth were also evident in small-size particles and
      included the depletion of low molecular weight n-alkanes and low chlorinated PCB
      congeners as well as a decrease of the fossil to pyrolytic PAHs ratio. Unusual
      increases of concentrations were observed at mid-depths (900-1100 m), indicating
      additional particle inputs, either by in-situ formation or by advective transport
      from the Mediterranean. The latter was recognized because small-size particles
      within these water veins exhibited distribution patterns out of the vertical
      sequence and similar to those of deep Mediterranean waters. An input of 8 and 0.5
      tons per year of the above PAH and PCB compounds, respectively, has tentatively
      been calculated as the contribution of these Mediterranean waters to the
      Northeastern Atlantic.

PMID- 11452593
TI  - Selective trapping of organochlorine compounds in mountain lakes of temperate
      areas.
AB  - The study of fish concentrations and sediment inventories in 19 European high
      mountain lakes (40-67 degrees N) shows that a fraction of organochlorine
      compounds (OCs), the less volatile compounds (LVC; subcooled liquid vapor
      pressure < or = 10(-2.5) Pa), are trapped in the higher locations. This general
      trend is not significantly influenced by possible local sources. Compound
      distribution is related to average air temperatures. The phase-change
      pseudoenthalpies calculated from the sediment inventories closely match the
      summed theoretical volatilization and dissolution enthalpies. This fractionation
      effect is responsible for the accumulation of high concentrations of the LVC, the
      more persistent and toxic according to literature data, in organisms inhabiting
      sites far from the locations of synthesis or use.

PMID- 11452594
TI  - Partial degradation of phenol by advanced electrochemical oxidation process.
AB  - The partial electrocatalytic degradation of phenol to organic acids has been
      investigated using an undivided electrolytic reactor with a beta-PbO2 anode
      containing fluorine resin. It was found that the decrease of benzoquinone (BQ)
      formed during phenol degradation and the acceleration of the process from phenol
      to organic acids are possible under an optimized operating condition. A possible
      pathway for phenol degradation was proposed, and a mathematical model for phenol
      and BQ evolution was developed. Operating parameters such as initial pH, current
      density, and temperature of the reaction were found to greatly impact the
      degradation rate of the phenol and even the pathway. Higher removal rate of
      phenol and BQ can be achieved at an appropriate temperature and higher current
      density in acidic medium preferably at pH 4. Under these conditions, phenol would
      be more likely degraded in the pathway from phenol to organic acids rather than
      through the BQ. When phenol is completely removed, the toxicity of the wastewater
      would be lessened suitable for biological process treatment. Accounting for the
      decrease of instantaneous current efficiency (ICE) during degradation, partial
      degradation would be highly economical for wastewater treatment, which would be
      an alternative process in practical application.

PMID- 11452595
TI  - Comparative analysis of PAH:DNA adducts formed in lung of mice exposed to neat
      coal tar and soils contaminated with coal tar.
AB  - 7H-Benzo[c]fluorene (benzo[c]fluorene) is a major DNA adduct forming component of
      coal tar in lung of mice. The present study evaluated the types of PAH:DNA
      adducts formed from different neat coal tar samples and soils contaminated with
      coal tar. Mice were fed diets containing coal tar either neat or as a contaminant
      in an environmental soil sample for 14 days, and the types of chemical:DNA
      adducts formed in lung were evaluated using 32P-postlabeling and HPLC analysis.
      Three major DNA adducts derived respectively from benzo[b]fluoranthene (B[b]F),
      benzo[a]pyrene (B[a]P), and benzo[c]fluorene were detected in three of the four
      neat coal tar samples evaluated. In contrast, only a single major DNA adduct
      derived from benzo[c]fluorene was observed with the remaining tar sample.
      Ingestion of coal tar contaminated soil resulted in DNA adducts primarily derived
      from benzo[c]fluorene and B[b]F; a B[a]P derived DNA adduct was not detected. The
      DNA adducts derived from benzo[c]fluorene and B[b]F but not B[a]P were also
      observed with animals fed methylene chloride extracts of three of these soils but
      not the one designated A1000H soil. However, the extract of A1000H resulted in a
      B[a]P:DNA adduct being detected along with adducts formed from B[b]F and
      benzo[c]fluorene. The selective formation of the benzo[c]fluorene:DNA adduct with
      coal tar contaminated soils indicates that the in vivo systemic bioavailability
      and/or metabolism of benzo[c]fluorene is relatively high when compared to other
      DNA adducting hydrocarbons within coal tar. Benzo[c]fluorene may play a critical
      role in the potential of contaminated soil to induce a toxicological response in
      animals.

PMID- 11452596
TI  - A fluorescence spectroscopic study of phenanthrene sorption on porous silica.
AB  - Fluorescence spectroscopic characteristics of sorbed phenanthrene in porous
      silica provide information about its chemical state such as monomer vs dimer or
      higher aggregates, as well as a basis for high sensitivity detection. In this
      study, the chemical state and distribution of phenanthrene sorbed in two types of
      porous silica particles, mesoporous silica (365 microns particle diameter, 150 A
      average pore diameter) and microporous silica (custom synthethized, 1 micron
      particle diameter, 20 A pore diameter), is determined by fluorescence
      spectroscopy, fluorescence lifetime measurements, and scanning two-photon
      excitation fluorescence profiling. From the characteristic fluorescence emission
      spectra, it is found that at loading levels of < or = 4.7 mg/g
      (phenanthrene/silica) phenanthrene exists as monomers in both meso- and
      microporous silica particles for phenanthrene loaded from super critical CO2
      (SCF). Two-photon excitation fluorescence intensity distribution profiles
      indicate that for the mesoporous silica particles phenanthrene is adsorbed
      throughout the entire silica particle. Introduction of water into phenanthrene
      loaded mesoporous silica particles causes instantaneous conversion of
      phenanthrene from monomer to crystalline form at phenantherene loading levels >
      or = 4.7 micrograms/g due to hydration of the silica surface. In this process,
      sorption of water molecules expels phenanthrene from the surface sorption sites
      and causes localized phenanthrene concentration beyond its solubility limit,
      resulting in crystallization. In comparison this fast conversion is not observed
      for phenanthrene-loaded microporous silica particles that show extremely slow
      conversion even for phenanthrene loading levels as high as 4.7 mg/g. This
      difference is interpreted as reflecting hindered diffusion of phenanthrene in the
      nearly monodispersed micropores with pore sizes close to the molecular diameter
      of phenanthrene.

PMID- 11452597
TI  - Degradation of alpha-pinene on Tenax during sample storage: effects of daylight
      radiation and temperature.
AB  - The behavior of alpha-pinene sampled on adsorption cartridges filled with Tenax
      TA has been investigated in relation to different storage conditions, focusing on
      daylight radiation and temperature. After sampling, the respective cartridges
      containing the terpene were placed in sunlight on the windowsill for up to 1
      month. Corresponding samples have been wrapped in aluminum foil to prevent the
      influence of daylight radiation. Additional sample cartridges with alpha-pinene
      were stored in the refrigerator at 4 degrees C and a freezer at -18 degrees C.
      All cartridges were analyzed using thermodesorption injection onto a gas
      chromatograph, and the compounds were detected using either a cryocondensation
      interface to a Fourier transform infrared-spectrometer (GC/FT-IR) or the flame
      ionization detector (FID). In summary, 12 compounds were detected and identified,
      from which eight were products that were formed on Tenax through different
      mechanisms. Two compounds seemed to be formed under the influence of daylight
      radiation, while the others appear to be mainly autoxidation products. Estimates
      after 1 month of storage showed recoveries of over 99% for wrapped samples, while
      for unwrapped cartridges only about 88% of alpha-pinene was found. A pattern of
      up to five compounds was found that can be used as an indicator for storage
      reactions.

PMID- 11452598
TI  - Photoproduction of hydrated electron from constituents of natural waters.
AB  - The wavelength dependence for the photoproduction of the hydrated electron (e
      (aq)) from various humic and fulvic acids and from natural waters was determined,
      employing a method that converts e-(aq) to a methyl radical that is detected
      fluorimetrically as the O-methylhydroxylamine of a stable nitroxide. Quantum
      yields for e-(aq) production from potassium ferrocyanide and N,N-dimethylaniline
      are in agreement with previously reported values. The quantum yields for
      production of e-(aq) from colored dissolved organic matter (CDOM) decrease
      precipitously with increasing wavelength with the rate of decline increasing in
      the order: humic acid < fulvic acid < natural water in the UV-B region. For
      Suwannee River fulvic acid, quantum yields ranged from 7.9 x 10(-6) at 366 nm to
      1.9 x 10(-4) at 296 nm indicating that previously reported values for e-(aq)
      production from CDOM involving laser sources of irradiation are high due to
      experimental artifact. Apparent natural water quantum yields at 296 nm are higher
      than those for humic substances, ranging from 9.4 x 10(-5) to 3.7 x 10(-3)
      depending on location. The highly absorbing waters of the Delaware and Chesapeake
      Bays show insignificant production of e-(aq). These results indicate that the
      hydrated electron, through its reaction with dioxygen, is not a significant
      source of hydrogen peroxide in many natural waters and that humic substances may
      not be the principal source of e-(aq) production.

PMID- 11452599
TI  - Modeling competitive cation exchange of aromatic amines in water-saturated soils.
AB  - Competitive association to several components of soil through ion exchange
      processes influences the fate of organic cations in the environment. To examine
      these processes, the distributions of aniline and 1-aminonaphthalene between
      aqueous 5 mM CaCl2 solutions and three different Indiana soils were evaluated.
      Solute ratios (Sr) of aniline to 1-aminonaphthalene of 0.4-4.7 were employed, and
      the soil solutions ranged in pH from 2.7 to 7.5, with all measurements made 24 h
      after the introduction of the chemicals to the soils. Two previously proposed
      equilibrium models--the two-site (TS) and distributed parameter (DP) models--were
      modified to predict competition. These models assume instantaneous equilibrium of
      the following reversible processes: (i) acid dissociation of the protonated
      organic base (BHaq+) in the aqueous phase; (ii) ion exchange on the soil between
      the protonated organic base and inorganic divalent cations (Daq2+ = Caaq2+ +
      Mgaq2+); and (iii) partitioning of the nonionic species of aniline (Baq) to soil
      organic carbon. The TS model is a general mass action model that does not take
      into consideration cation exchange site heterogeneity, whereas the DP model
      considers association constants to these sites to be distributed in a log-normal
      fashion. To describe competition for cation exchange sites within the DP model,
      it was necessary to add a correlation coefficient (rho) that relates the ion
      exchange association constant (KBH) probability density distribution functions of
      the two compounds. The value of rho is characteristic of each soil. Results
      indicate that competition has a greater effect at low pH values, where ion
      exchange is the predominant process. For all cases, these models capture the
      general trends in the soil-water distribution data of both amines. The DP model
      also captures the nonlinearity of the 1-aminonaphthalene isotherms at low pH
      while at the same time capturing the nearly linear isotherms of aniline as a
      competing organic base.

PMID- 11452600
TI  - Biodegradation of non-desorbable naphthalene in soils.
AB  - The degradation of naphthalene was studied in soil-slurry systems, and a
      quantitative model was developed to evaluate the bioavailability of sorbed-phase
      contaminant. Four soils with different organic matter contents were used as
      sorbents. Two naphthalene-degrading organisms, Pseudomonas putida G7 and NCIB
      9816-4, were also selected. Sorption isotherms and single and series dilution
      desorption studies were conducted to evaluate distribution coefficients,
      desorption parameters, and the amount of non-desorbable naphthalene.
      Biodegradation kinetics were measured in soil extract solutions and rate
      parameters estimated. Bioavailability assays involved establishing sorption
      equilibrium, inoculating the systems with organisms, and measuring naphthalene
      concentrations in both sorbed and dissolved phases over time. For all four soils,
      the sorption isotherms were linear, and desorption could be described by a model
      involving three types of sites: equilibrium, nonequilibrium, and non-desorption.
      Enhanced bioavailability, as evidenced by faster than expected degradation rates
      based on liquid-phase concentrations, were observed in soils with the higher
      sorption distribution coefficients. These observations could be described using
      model formulations that included solid-phase degradation. In all soils studied,
      degradation of non-desorbable naphthalene was observed.

PMID- 11452601
TI  - The human footprint.

PMID- 11452602
TI  - Bonding of Hg(II) to reduced organic sulfur in humic acid as affected by S/Hg
      ratio.
AB  - Organic matter is an important sorbent of heavy metals in soils and sediments.
      The heterogeneity of organic matter, including the presence of various reactive O
      , N-, and S-bearing ligands, makes it difficult to precisely characterize the
      nature of metal-ligand binding sites. The objective of this research was to
      characterize the extent and nature of Hg(II) bonding with reduced organic S in
      soil organic matter. Sulfur-rich humic acid (0.7 +/- 0.1 mol of S kg-1) was
      extracted from samples of surface soil from a marine wetland. Synchrotron X-ray
      absorption near-edge structure (XANES) analysis at the S K edge indicated that 70
      +/- 3 mol % of the organic S was in a reduced oxidation state. Aqueous solutions
      containing 2 mmol of Hg kg-1, 0.1 M NaNO3, and humic acid added at various S/Hg
      molar ratios at pH 5.60 +/- 0.02 were characterized using extended X-ray
      absorption fine structure (EXAFS) spectroscopy at the Hg LIII edge. Spectral
      fitting showed that as the total S/Hg ratio increased from 0.6 to 5.6 (reduced
      S/Hg of 0.4-4.0), the fraction of Hg-S bonding relative to Hg-O (or Hg-N) bonding
      increased from 0.4 to 0.9. Results demonstrated preferential bonding of Hg(II) to
      reduced organic S sites and indicated that multiple sulfur ligands were
      coordinated with Hg2+ ions at high S/Hg ratios, which corresponded to low levels
      of complexed Hg(II).

PMID- 11452603
TI  - C1-C5 organic acid emissions from an SI engine: influence of fuel and air/fuel
      equivalence ratio.
AB  - A spark ignition engine is used to study the impact of fuel composition and of
      the air/fuel equivalence ratio on exhaust emissions of organic acids. Fuel blends
      are composed from eight hydrocarbons (n-hexane, 1-hexene, cyclohexane, n-octane,
      2,2,4-trimethylpentane, toluene, o-xylene, and ethylbenzene) and four oxygenated
      compounds (methanol, ethanol, 2-propanol, and MTBE). Exhaust formic acid is
      slightly enhanced from aromatics and oxygenated compounds; acetic acid is
      slightly enhanced from the oxygenated fuel components; propionic acid comes from
      fuel aromatic compounds, and butyric acid originates from fuel o-xylene. Acrylic
      and isovaleric acids are also detected in lower concentrations. It is unlikely
      that oxygenated compounds are precursors to the formation of organic acids, but
      they facilitate their formation because they facilitate the oxidation of other
      fuel components. Exhaust concentration of formic acid is also related to exhaust
      oxygen and exhaust temperature. Air/fuel equivalence ratio increases the exhaust
      concentration of formic, acetic acid (for the fuels without oxygenated
      compounds), and acrylic acid and decreases the concentration of isovaleric acid.
      The acetic (for the oxygenated fuels), propionic, and butyric acids are at a
      maximum at stoichiometry.

PMID- 11452604
TI  - Role of disinfectant concentration and pH in the inactivation kinetics of
      Cryptosporidium parvum oocysts with ozone and monochloramine.
AB  - The objective of this study was to investigate the effect of disinfectant
      concentration and pH on the inactivation kinetics of Cryptosporidium parvum
      oocysts with ozone, monochloramine, and ozone/monochloramine at 20 degrees C.
      Experimental results revealed that the CT (product of disinfectant concentration
      and contact time) required to achieve a certain level of C. parvum inactivation
      was unique, thus demonstrating the validity of the CT concept for these single
      disinfectant and sequential disinfection processes for the range of experimental
      conditions investigated. Inactivation curves were represented accurately by a
      delayed Chick-Watson expression consistent with the CT concept. No pH dependence
      was observed for primary inactivation with ozone in the pH range of 6-10 or
      primary and secondary inactivation with monochloramine at pH values of 8 and 10.
      Oocyst resistance to chemical disinfectant attack was found to vary among oocysts
      lots as well as with oocyst aging within a given lot. The synergy observed for
      sequential disinfection with ozone/monochloramine suggested that monochloramine
      might be reacting with some of the same chemical constituents, both vital and
      nonvital, of the oocyst wall and/or cavity that also react with ozone. If so,
      partial completion of these reactions by the primary disinfectant would have
      resulted in the disappearance of the lag phase and the faster rate of
      inactivation observed for the secondary disinfectant.

PMID- 11452605
TI  - Indoor chemistry: ozone and volatile organic compounds found in tobacco smoke.
AB  - The deliberate generation of ozone in indoor settings has been promoted as a
      method to reduce the concentration of indoor pollutants. The present study
      examines the effect of ozone on a subset of volatile organic compounds (VOCs)
      found in tobacco smoke. The decays of these compounds were measured in a static
      room-sized chamber: (1) in the absence of ozone, (2) in the presence of moderate
      ozone concentrations (< 0.115 ppm), and (3) in the presence of high ozone
      concentrations (< 1.4 ppm). At moderate ozone concentrations there was little
      effect on the monitored VOCs. At high ozone concentrations there was a small,
      unanticipated reduction in the concentration of some of the saturated VOCs,
      apparently caused by OH radicals produced as a consequence of the ozone/alkene
      reactions. There was also a much larger reduction in the concentrations of those
      compounds with unsaturated carbon bonds. However, this reduction was largely
      matched by an increase in the concentration of a number of aldehydes. Some of
      these aldehydes are more potent irritants than their precursors. Furthermore,
      even a relatively small ventilation rate (approximately 0.1 h-1) would produce a
      greater reduction in the monitored VOCs than that produced by a moderate amount
      of ozone.

PMID- 11452606
TI  - Effect of solute concentration on sorption of polyaromatic hydrocarbons in soil:
      uptake rates.
AB  - The effect of solute concentration on sorption kinetics may be a factor in
      determining bioavailability and transport of organic pollutants in soils and
      sediments, but there is conflict in the literature over whether sorption is
      concentration-dependent. Sorption of phenanthrene and pyrene to seven soils
      ranging in organic carbon (OC) content from 0.18 to 43.9% was studied. Careful
      analysis revealed that experimentally the normalized rate of approach to
      equilibrium for compounds exhibiting a concave-down (with respect to the solute
      concentration axis) nonlinear isotherm increases with concentration. However, the
      effect is rather small and is most apparent when the fraction of total solute
      finally taken up by the solid (F) is low. The explanation is rooted in the
      nonlinearity of the isotherm and the finite-bath condition of the experiment and
      can be expressed in terms of two opposing effects. On the one hand, the apparent
      diffusivity of a (concave-down) nonlinearly sorbing compound within particles
      increases with concentration because its affinity for the solid phase decreases
      with increasing concentration. On the other hand, rates in finite-bath reactors
      carried out at the same liquid/solid ratio will suffer from a batch process
      temporal bias called the "shrinking gradient" effect. It is an artifact of the
      methodology and is due to gradient driving forces that slow the sorption rate as
      F declines. In nonlinear cases F declines as concentration increases. The
      shrinking gradient effect vanishes as the liquid/solid ratio approaches infinity.
      Although this effect is self-correcting when an appropriate nonlinear diffusion
      model is applied, consensus about such models has not yet been achieved. To
      provide bounds for the shrinking gradient effect in finite-bath systems
      semiempirically, two models that give lower and upper bounds of the
      characteristic sorption time tau in the limit of infinite bath have been
      employed: (a) a wetting front model, which assumes sorption is rate-limited by
      molecular migration, and (b) a fast diffusion model, which assumes a mass
      transfer resistance at the sorption site. The results are consistent with an
      intrinsic positive concentration dependence of sorption kinetics.

PMID- 11452607
TI  - Do roundup ready soybeans require more herbicide?

PMID- 11452608
TI  - Rhizosphere effects on microbial community structure and dissipation and toxicity
      of polycyclic aromatic hydrocarbons (PAHs) in spiked soil.
AB  - Phytoremediation of soils polluted with polycyclic aromatic hydrocarbons (PAHs)
      has so far neglected the possible role of the ubiquitous symbiotic associations
      between plant roots and fungi known as arbuscular mycorrhizas. A time course
      laboratory experiment with clover and ryegrass grown on spiked [500 + 500 + 50 mg
      kg-1 of anthracene, chrysene and dibenz(a,h)anthracene] soil demonstrated for the
      first time that dissipation of condensed PAHs may be enhanced in the presence of
      arbuscular mycorrhiza [66 and 42% reductions in chrysene and
      dibenz(a,h)anthracene, respectively, versus 56 and 20% reductions in
      nonmycorrhizal controls]. Addition of a surfactant accelerated initial PAH
      dissipation but did not attain final PAH concentrations below those obtained with
      nonmycorrhizal plants. Toxicity tests (earthworm survival and bioluminescence
      inhibition in Vibrio fischeri) indicated that mycorrhiza reduced the toxicity of
      PAHs and/or their metabolites and counteracted a temporally enhanced toxicity
      mediated by surfactant addition. Phospholipid fatty acid profiles demonstrated
      that the imposed treatments altered the microbial community structure and
      indicated that the mycorrhiza-associated microflora was responsible for the
      observed reductions in PAH concentrations in the presence of mycorrhiza.

PMID- 11452609
TI  - Validation of an arsenic sequential extraction method for evaluating mobility in
      sediments.
AB  - Arsenic (As) mobility and transport in the environment are strongly influenced by
      arsenic's associations with solid phases in soil and sediment. We have tested a
      sequential extraction procedure intended to differentiate the following pools of
      solid phase arsenic: loosely and strongly adsorbed As; As coprecipitated with
      metal oxides or amorphous monosulfides; As coprecipitated with crystalline iron
      (oxyhydr)oxides; As oxides; As coprecipitated with pyrite; and As sulfides.
      Additions of As-bearing phases to wetland and riverbed sediment subsamples were
      quantitatively recovered by the following extractants of the sequential
      extraction procedure: As adsorbed on goethite, 1 M NaH2PO4; arsenic trioxide
      (As2O3), 10 M HF; arsenopyrite (FeAsS), 16 N HNO3; amorphous As sulfide, 1 N HCI,
      50 mM Ti-citrate-EDTA, and 16 N HNO3; and orpiment (As2S3), hot concentrated
      HNO3/H2O2. Wet sediment subsamples from both highly contaminated wetland peat and
      less As-rich sandy riverbed sediment were used to test the extraction procedure
      for intra-method reproducibility. The proportional distribution of As among
      extractant pools was consistent for subsamples of the wetland and for subsamples
      of the riverbed sediments. In addition, intermethod variability between the
      sequential extraction procedure and a single-step hot concentrated HNO3/H2O2 acid
      digestion was investigated. The sum of the As recovered in the different
      extractant pools was not significantly different than results for the acid
      digestion.

PMID- 11452610
TI  - Effects of sulfur impregnation temperature on the properties and mercury
      adsorption capacities of activated carbon fibers (ACFs).
AB  - Laboratory studies were conducted to determine the role of sulfur functional
      groups and micropore surface area of carbon-based adsorbents on the adsorption of
      Hg0 from simulated coal combustion flue gases. In this study, raw activated
      carbon fibers that are microporous (ACF-20) were impregnated with elemental
      sulfur between 250 and 650 degrees C. The resulting samples were saturated with
      respect to sulfur content. Total sulfur content of the sulfur impregnated ACF
      samples decreased with increasing impregnation temperatures from 250 and 500
      degrees C and then remained constant to 650 degrees C. Results from sulfur K-edge
      X-ray absorption near-edge structure (S-XANES) spectroscopy showed that sulfur
      impregnated on the ACF samples was in both elemental and organic forms. As sulfur
      impregnation temperature increased, however, the relative amounts of elemental
      sulfur decreased with a concomitant increase in the amount of organic sulfur.
      Thermal analyses and mass spectrometry revealed that sulfur functional groups
      formed at higher impregnation temperatures were more thermally stable. In
      general, sulfur impregnation decreased surface area and increased equilibrium Hg0
      adsorption capacity when compared to the raw ACF sample. The ACF sample treated
      with sulfur at 400 degrees C had a surface area of only 94 m2/g compared to the
      raw ACF sample's surface area of 1971 m2/g, but at least 86% of this sample's
      surface area existed as micropores and it had the largest equilibrium Hg0
      adsorption capacities (2211-11,343 micrograms/g). Such a result indicates that
      400 degrees C is potentially an optimal sulfur impregnation temperature for this
      ACF. Sulfur impregnated on the ACF that was treated at 400 degrees C was in both
      elemental and organic forms. Thermal analyses and CS2 extraction tests suggested
      that elemental sulfur was the main form of sulfur affecting the Hg0 adsorption
      capacity. These findings indicate that both the presence of elemental sulfur on
      the adsorbent and a microporous structure are important properties for improving
      the performance of carbon-based adsorbents for the removal of Hg0 from coal
      combustion flue gases.

PMID- 11452611
TI  - A kinetic study of the oxidation of S(IV) in seawater.
AB  - Flue gas desulfurization by means of SO2 absorption in seawater is a well-known
      process. However, it can be optimized if the oxidation kinetics of dissolved
      S(IV) is known. Laboratory reactor experiments in which the pH and temperature
      were controlled, determined the oxidation kinetics of S(IV) in seawater. This
      study conclusively shows that the order with respect to S(IV) is one and that the
      order with respect to oxygen is zero. The kinetic constant depends greatly on the
      temperature and on the pH; consequently, the activation energy and a relationship
      between the kinetic constant and the hydrogen proton concentration (2 < pH < 6)
      were also obtained.

PMID- 11452612
TI  - Determination of solid-phase loading for the removal of metal ion from effluents
      using fixed-bed adsorbers.
AB  - The sorption of cadmium and copper ions from aqueous solutions onto bone char
      using fixed-bed adsorbers has been studied. A film-pore diffusion model has been
      utilized to predict theoretical breakthrough curves, which are compared with
      experimental breakthrough curves by means of error analysis. The key parameters
      for correlating the theoretical model are the external film mass-transfer
      coefficient (kf), the effective diffusion coefficient (Deff), and the solid-phase
      loading (q). The kf is determined from fixed-bed empirical correlations, and Deff
      is determined by a best-fit optimization routine. The q value has traditionally
      been determined using the equilibrium isotherm, which is applicable when the
      column adsorbent reaches equilibrium, or using the breakthrough curve mass
      balance when the column does not reach equilibrium. The breakthrough curve mass
      balance method needs experimental curves for each system and is not a practical
      solution for general design models. This paper presents two novel predictive
      equations for q in terms of process variables. The accuracy of the equations is
      sufficient for application in design models for nonequilibrium and equilibrium
      systems.

PMID- 11452613
TI  - Mass transport effects on the kinetics of nitrobenzene reduction by iron metal.
AB  - To evaluate the importance of external mass transport on the overall rates of
      contaminant reduction by iron metal (Fe0), we have compared measured rates of
      surface reaction for nitrobenzene (ArNO2) to estimated rates of external mass
      transport in a permeable reactive barrier (PRB). The rate of surface reaction was
      measured at a polished Fe0 rotating disk electrode (RDE) in an electrochemical
      cell, and the rate of mass transport was estimated from a correlation for mass
      transport in packed-bed reactors. The kinetics of ArNO2 reduction were studied in
      pH 8.4 borate buffer at a potential below which an oxide film would form. The
      cathodic current measured in this system was dependent on the electrode rotation
      rate, and the measured first-order heterogeneous rate coefficient for surface
      reaction [krxn = (1.7 +/- 0.2) x 10(-3) cm s-1] was about 10 times faster than
      the first-order mass transport rate coefficient (kmt approximately 2 x 10(-4) cm
      s-1) estimated for PRBs. The similarity between rates of surface reaction and
      mass transport suggest that it may be important to consider mass transport
      processes in the design of PRBs for contaminants such as nitroaromatics that are
      highly reactive with Fe0.

PMID- 11452614
TI  - Salt-thermal zeolitization of fly ash.
AB  - The molten-salt method has been recently proposed as a new approach to
      zeolitization of fly ash. Unlike the hydrothermal method, this method employs
      salt mixtures as the reaction medium without any addition of water. In this
      study, systematic investigation has been conducted on zeolitization of fly ash in
      a NaOH-NaNO3 system in order to elucidate the mechanism of zeolite formation and
      to achieve its optimization. Zeolitization of fly ash was conducted by thermally
      treating a powder mixture of fly ash, NaOH, and NaNO3. Zeolitization of fly ash
      took place above 200 degrees C, a temperature lower than the melting points of
      salt and base in the NaOH-NaNO3 system. However, it was uncertain whether the
      reactions took place in a local molten state or in a solid state. Therefore, the
      proposed method is renamed the "salt-thermal" method rather than the "molten
      salt" method. Mainly because of difficulty in mobility of components in salt
      mixtures, zeolitization seems to occur within a local reaction system. In situ
      rearrangement of activated components seems to lead to zeolite formation.
      Particle growth, rather than crystal growth through agglomeration, resulted in no
      distinct morphologies of zeolite phases. Following are the optimal zeolitization
      conditions of the salt-thermal method: temperature, 250-350 degrees C; time, 3-12
      h; weight ratio of NaOH/NaNO3, 0.3-0.5; weight ratio of NaNO3/fly ash, 0.7-1.4.
      Therefore, it is clear from this work that the salt-thermal method could be
      applied to massive zeolitization of fly ash as a new alternative method for
      recycling this waste.

PMID- 11452615
TI  - The leaching behavior of cement stabilized air pollution control residues: a
      comparison of field and laboratory investigations.
AB  - The factors controlling leachate composition of cement stabilized air pollution
      control (APC) residues (41% APC residues, 22% cement, 3% Na2CO3, and 32% water,
      w/w) have been investigated both in the laboratory and in a pilot landfill. Batch
      leaching and tank leaching tests were carried out in the laboratory in order to
      determine solubility controlling phases and diffusion controlled species. The
      major species Ca, SO4, Al, and Si could be partially modeled by assuming calcium
      silicate hydrate (C-S-H), portlandite, and ettringite to be the solubility
      controlling phases both in field and laboratory. There were obviously additional
      minerals that could not be taken into account in calculations because of the lack
      of data. The determined effective diffusion coefficients (De) for Na and K (2.18e
      12 and 5.43e-12 m2s-1) were used to model field concentrations. Agreement with
      field data was good. Heavy metal concentrations were in the range of 10(-8) mol
      dm-1 (Cd, Co, Cu, Mn, Ni) to 10(-6) mol dm-1 (Mo, Pb, W, Zn) in all experiments
      and often lower in the field leachate than expected from batch experiments. In
      laboratory experiments, the solubility of Mo and W was most probably controlled
      by their calcium metalates, Cu by CuO, Ni by Ni(OH)2, and Zn probably by a Zn
      containing C-S-H phase. In the field, diffusion seems to control Mo and W
      leachability, with calculated De values of 3.49e-14 and 1.35e-15 m2s-1.

PMID- 11452616
TI  - Gas-phase photocatalytic oxidation of dichlorobutenes.
AB  - Gas-phase photocatalysis of 1,4-dichlorobut-2-enes and 3,4-dichlorobut-1-ene
      (DCB) has been studied using TiO2 and 3% WO3/TiO2 supported on SiO2. DCB was
      found to oxidize efficiently over these catalysts; however, only low rates of CO2
      formation were observed. With these chlorinated hydrocarbons, the catalysts were
      found to deactivate over time, probably via the formation of aldol condensation
      products of chloracetaldehyde, which is the predominant intermediate observed.
      The variation in rate and selectivity of the oxidation reactions with O2
      concentration is reported and a mechanism is proposed. Using isotope ratio mass
      spectrometry, the initial step for the DCB removal has been shown not to be a
      carbon bond cleavage but is likely to be hydroxyl radical addition to the carbon
      carbon double bond.

PMID- 11452617
TI  - Catalytic wet oxidation of phenol: kinetics of phenol uptake.
AB  - Catalytic phenol oxidation in aqueous phase under intermediate temperature and
      pressure has been carried out in order to determine the kinetic model of phenol
      uptake rate. The catalyst employed here was a commercial one based on copper
      supplied by Engelhard (Cu-0203T). Operational variables have been studied in the
      following ranges: temperature from 127 to 180 degrees C, oxygen pressure from 3.2
      to 16 bar, initial phenol concentration from 680 to 1200 ppm, and catalyst
      concentration from 0 to 1550 g/L of liquid phase. Because of the wide interval
      here employed for the catalyst concentration, two experimental setups have been
      used: a basket stirred tank reactor (BSTR) with the liquid phase in batch and an
      integral fixed-bed reactor (FBR) with co-current upflow of gas and liquid phases.
      An important influence of the reaction in the bulk liquid was obtained in both
      types of reactor. This fact has been taken into account in the kinetic model
      according to different approaches. The first approach was a breakup of the
      reaction rate in two kinetic expressions, considering the homogeneous and
      heterogeneous contribution separately; the second approach was empirical where
      the reaction rate is a potential function of the catalyst concentration. It was
      found that the extent of reaction in the bulk liquid is also influenced by the
      catalyst concentration and that the first approach is not able to adequately
      predict the experimental results. Finally a kinetic model, based on the second
      approach, was discriminated, with a power law for the catalyst concentration with
      an order about 0.4. This model fits quite well the experimental data obtained in
      both experimental setups, BSTR and FBR, throughout the wide range of variables
      studied.

PMID- 11452618
TI  - A laboratory study of surfactant flushing of DNAPL in the presence of
      macroemulsion.
AB  - Computed tomography (CT) monitored experiments are conducted in a three
      dimensional water-saturated sandpack to evaluate the performance of a
      biodegradable surfactant (Glucopon-425N) in recovering a residually trapped dense
      nonaqueous phase liquid (DNAPL) tetrachloroethylene (PCE) from two sandpacks.
      Effects of flow rate, surfactant concentration, and pore size on the remediation
      process are evaluated. Axial variation in porosity of a sandpack has significant
      effect on the residual distribution of DNAPL in the sandpack and its subsequent
      recovery. DNAPL is recovered in two stages in general: mobilization followed by
      macroemulsion-solubilization. Mobilized DNAPL is recovered as a free-phase for
      all the experiments in the 30-mesh sandpack and only limited mobilization was
      observed in the 50-mesh sandpack. The dominant mechanism of recovery is
      macroemulsion flow (accounts for 46-86% of solubilized-emulsified PCE) in both
      the sands which leads to much higher PCE effluent concentration than the
      solubility limit as determined in batch solubilization studies. The effluent PCE
      concentration in the later stage depends on surfactant concentration but not on
      surfactant flow rate or pore size.

PMID- 11452619
TI  - Ozone as a cleanup tool.

PMID- 11452620
TI  - Removal of chemical contaminants from water to below USEPA MCL using fiber glass
      supported activated carbon filters.
AB  - A new, low-cost fiber glass supported activated carbon (FGAC) filter has been
      prepared that displays enhanced adsorption characteristics for the removal of
      BTEX (benzene, toluene, ethylbenzene, and p-xylene) from water to below maximum
      contaminant level (MCL) regulated by USEPA and two chemical warfare agent
      simulants (diisopropylmethyl phosphonate and 2-chloroethyl ethyl sulfide) to
      barely detectable levels. Breakthrough curves for both the FGAC filter and a
      commercially available granular activated carbon (GAC) filter containing equal
      weights of adsorbent show that the FGAC filter has greatly improved kinetics of
      adsorption over the GAC filter for all six chemical contaminants. Benzene
      breakthrough curves showed the FGAC filter effluent to contain less than one ppb
      as compared to several parts per million in the GAC filter effluent. This was 2
      orders of magnitude better than the GAC and represents a major advance in
      generating good water quality for the military as well as the general public. The
      FGAC filter showed a much lower pressure drop and could be completely regenerated
      at least 6 times by heating to 190 degrees C under vacuum.

PMID- 11452621
TI  - Photoassisted electrochemical degradation of organic pollutants on a DSA type
      oxide electrode: process test for a phenol synthetic solution and its application
      for the E1 bleach Kraft mill effluent.
AB  - In this paper, the performance of a photoassisted electrolysis process, for the
      degradation of organic pollutants, is investigated. Results obtained in this work
      have shown that the thermally prepared anode of titanium, coated with
      70TiO2/30RuO2, exhibits photoactivity and may be used for the treatment of
      effluents. A synthetic phenol aqueous solution and a real paper mill industry
      effluent were treated. Kinetic analysis showed a synergetic effect of
      electrolysis and photocatalysis and degradation rates are an order of magnitude
      greater than the sum of the results reached by using both processes individually.
      Using a 125 W mercury bulb and 20 mA cm-2, the phenol concentration decayed 85%
      in 90 min and 70% reduction of TOC was obtained. In the application of the
      treatment process for the degradation of the E1 bleach Kraft mill effluent, total
      phenols were practically eliminated in a short period of processing time, and
      color, usually resistant to biological treatment, was reduced to 10% from its
      initial value measured in terms of absorbance. Reductions of AOX, COD, and BOD by
      25%, 30%, and 35%, respectively, were also observed.

PMID- 11452622
TI  - Accumulation forms of Zn and Pb in Phaseolus vulgaris in the presence and absence
      of EDTA.
AB  - The internalized speciation of Zn and Pb in roots and leaves of Phaseolus
      vulgaris grown in zinc sulfate, zinc EDTA, lead nitrate, and lead EDTA solutions
      were studied by electron microscopy (Zn) and extended X-ray absorption fine
      structure (EXAFS) spectroscopy (Zn and Pb). Zn was predominantly present as Zn
      phosphate dihydrate in the roots and leaves of the plant regardless of its form
      in solution. Pb was predominantly found in the leaves as cerussite (lead
      carbonate) when the plant was grown in Pb nitrate solution and as a mixture of
      PbEDTA and an undetermined species in contact with PbEDTA solution. Therefore,
      Phaseolus vulgaris is able to dissociate totally (Zn) or partly (Pb) the two
      metal-EDTA complexes from the nutrient solution and to bind these metals in other
      forms.

PMID- 11452623
TI  - The arsenic threat worsens.

PMID- 11452624
TI  - Mr. Bush charts his energy future.

PMID- 11452625
TI  - Going like gangbusters: transnational tobacco companies "making a killing" in
      South America.
AB  - This article reports on the recent growth of transnational tobacco companies
      (TTCs) in South America. Although some scholarly attention has been directed
      toward such growth in Asia and eastern Europe, South America has also been
      targeted by the TTCs' aggressive expansionist practices in recent years. Fighting
      "Big Tobacco" is entirely different from combating most public health problems.
      Unlike cigarettes, most infectious diseases and maternal and child health
      problems never provide profits to transnational corporations and governments.
      Also, most public health problems (with alcohol being another notable exception)
      are not exacerbated by extensive advertising campaigns that promote the cause of
      the health problems. Supported by data gathered during three months of fieldwork
      in Ecuador, Peru, Chile, and Argentina in 1997, this article suggests that the
      TTCs' marketing strategies override cultural differences in the choices people
      make regarding smoking and health. Combining critical medical anthropology and
      public health, this article concludes that unless dramatic actions are taken, an
      avoidable outbreak of tobacco-related diseases will eventually reach epidemic
      proportions on the South American continent. It is also a "call to arms" for more
      medical anthropologists to investigate tobacco-related matters around the world.

PMID- 11452626
TI  - Gendering local knowledge: medicinal plant use and primary health care in the
      Amazon.
AB  - Local knowledge is becoming increasingly important in primary health care
      projects. However, these projects often incorporate local knowledge in an
      uncritical manner. One area where this is apparent is in the lack of attention
      paid to the gendered nature of local knowledge. I use one example, women's
      knowledge and use of medicinal plants in a low-income community in the Brazilian
      Amazon, to illustrate the links among authority, knowledge, and gender. In this
      article I argue that policy makers must pay attention to the relationships among
      authority, gender, and local knowledge and examine how the use of local knowledge
      in development strategies can affect existing (gendered) power relationships.
      Women's roles as managers of household health (which includes medicinal plant
      use) are a source of authority for them. Because of that, the way in which local
      knowledge is incorporated into primary health care programs can have a
      significant impact on women's authority.

PMID- 11452627
TI  - How Japanese women talk about hot flushes: implications for menopause research.
AB  - An unanticipated onomatopoeic expression emerged during ethnographic interviews
      with Japanese women about menopausal symptoms. At the same time, a newly coined
      term for hot flush, derived from English, started appearing in Japanese media.
      These two independent linguistic phenomena led me to speculate on what linguistic
      expression of physical sensations may reveal about social forces in a given
      society. This report examines the complexities involved in studying physiological
      symptoms. The multiple and intertwined variables--including economics, politics,
      social organization, and language--involved in translating physiological symptoms
      cross-culturally have been well recognized. But how to study these variables
      remains a challenge. This article offers a case study of what careful attention
      to verbal expression may tell us. My argument underscores the social fact that
      the expressions people choose to use vary according to their reasons for
      communicating and that their motivations for verbalizing symptoms (hot flush, in
      this case) depend on the priorities and sanctions of the society in which they
      live. These factors must be given due consideration when assessing any symptoms
      of the individual body.

PMID- 11452628
TI  - The children of Yemen: bodies, medicalization, and nation-building.
AB  - Yemenite Jews were among the many immigrants from Arab countries who were flown
      to Israel after its establishment in 1948. Following many complaints regarding
      the disappearance of Yemenite children from hospitals and schools in the transit
      camps where the new immigrants were kept in the 1950s, a governmental
      investigation committee was established in 1995. This article provides a
      preliminary description, from an anthropological perspective, of what is called
      in Israel the "Yemenite children affair." My analysis focuses on interviews with
      Yemenite Jews, describing how the bodies of new immigrants were medicalized and
      commodified and how immigrants and their families have come to resist these
      processes. I then focus on the role of the Israeli medical profession in
      promoting national goals and maintaining collective identity.

PMID- 11452629
TI  - "You ate all that!?": caretaker-child interaction during children's assisted
      dietary recall interviews.
AB  - Young children's dietary recalls generally are conducted with a guardian present,
      but how this contributes to data accuracy is unclear. Furthermore, some
      assumptions underlying the preference for guardian presence may be unfounded. To
      investigate the range of guardian-child interactions within the diet recall
      setting, we examined transcriptions of guardian-assisted recalls conducted with
      34 children aged 7-11 whose households were enrolled with the San Diego site of
      the Olestra Post-Marketing Surveillance Study (OPMSS). Although guardians did add
      to the breadth of data collected, children were quite knowledgeable about their
      diets. Moreover, they sometimes rejected guardian suggestions, and guardians
      generally could not provide assistance when children requested it. Guardian-child
      negotiations reflected cultural understandings regarding children, caretaking,
      and guardian-child power structures as well as food, and sometimes interviewers
      had to make very subjective data classification decisions. Suggestions for
      improving dietary recall methods are provided. Findings are relevant for other
      research methods involving children.

PMID- 11452630
TI  - "They don't have to suffer for me": why dialysis patients refuse offers of living
      donor kidneys.
AB  - In the present climate of organ shortage, high demand for kidney transplants, and
      better clinical outcomes from living donors, health care professionals expect and
      encourage patients to accept offers of living related donor (LRD) kidneys. When
      patients decide not to adhere to this course of treatment, scholars and policy
      makers may question why, given that it delays their chances of receiving a
      transplant. This article reports on patients' decisions to refuse LRD kidney
      offers. An 18-month study was conducted of treatment decisions by hemodialysis
      patients (N = 79). Fewer than half of those offered an LRD kidney (N = 64) were
      willing to accept it, suggesting that sociocultural factors inform decisions.
      Patients expressed concerns about the potential donors' well-being over their own
      and about compromising their relationships with the donors. This article
      concludes that social relations, emotions, and ethnomedical beliefs play an
      important role in patients' treatment decisions and thus contributes to the
      anthropology of decision making.

PMID- 11452631
TI  - The development of a closed-loop controlled functional electrical stimulation
      (FES) in gait training.
AB  - A closed-loop functional electrical stimulation (FES) system is developed to
      provide hemiplegic patients with a real-time stimulation to their muscles to
      prevent the drop-foot and the quadriceps weakness from happening during gait
      training. The FES is controlled by position sensors (ps) and triggered by
      footswitches (f) with real-time feedback. As the FES receives the signals from
      these sensors, it adjusts and outputs an optimum set of stimulation parameters
      automatically. One hemiplegic patient was recruited to conduct clinical
      evaluation and treated by using the new closed-loop FES system. It was revealed
      that the mean velocity, cadence, stride length, active ankle motion range, and
      functional ambulation category (FAC) improved significantly from 0.12 +/- 0.07 ms
      1, 40.3 +/- 18.3 steps min-1, 0.35 +/- 0.10 m, 15 degrees, level 2 to 0.42 +/-
      0.23 ms-1, 68.2 +/- 19.0 steps min-1, 0.70 +/- 0.22 m, 40 degrees, level 4
      respectively for the patient. A paired t-test indicated that differences in the
      electromyography (EMG) of the tibialis anterior and the quadriceps muscles
      between the patient's disabled (affected side) foot and normal (unaffected side)
      foot are not significant (p > 0.05) after 12 weeks of training. It is concluded
      that this new closed-loop FES system is capable of providing this hemiplegic
      patient with restoration to regular walking after appropriate gait training.
      Future studies, including randomized-controlled study, should be implemented to
      document the efficacy of this system.

PMID- 11452632
TI  - Monitoring of fluctuating airway obstruction and episodes of coughing by thoracic
      electrical impedance.
AB  - The most prominent feature of bronchial asthma is the fluctuating airway
      obstruction of the affected subjects. Cough is also one of the major symptoms of
      asthma, but of other conditions as well. The continuous registration of airway
      obstruction and coughing in the working or open-air environment or at the homes
      of the potential sufferers may help establish a sometimes elusive diagnosis. To
      this purpose we developed a method using a measurement of the changes in the
      chest basal electrical impedance (Z0). A portable device for long-term recording
      of the Z0 signal was built using a microprocessor system. In order to assess both
      gradual Z0 changes, suggestive of altering airway patency and coughing episodes
      (characterized by abrupt changes), a continuous analogue-to-digital conversion
      (ADC) loop with a sampling frequency of 16 Hz was programmed. After completion of
      the recording, the memory of the portable instrument can be downloaded to a PC
      system for assessment and analysis. Appropriate averaging and filtering
      procedures have been worked out. This device may be further upgraded to give out
      a signal when Z0 starts to increase, so as to prevent a full-blown asthmatic
      crisis.

PMID- 11452633
TI  - Numerical computation as a tool to aid thermographic interpretation.
AB  - Thermography is an non-invasive and a painless tool for the detection of breast
      cancer. However, performing and interpreting thermograms requires meticulous
      training. It was found that women with an abnormal thermogram are at a higher
      risk and have a poorer prognosis. One of the main drawbacks of the thermogram is
      the high incidence of false-positive results. The authors believe that the fault
      lies in misinterpretation of the thermogram, rather than the thermogram itself.
      The paper aims to show that computer simulations could be an adjunct tool to help
      the clinician in the interpretation. This would greatly reduce the false-positive
      diagnosis.

PMID- 11452634
TI  - A computerized data acquisition system for infusion devices--a clinical support
      tool, or a risk management tool?
AB  - A prototype computerized system for automatic data collection from multi-vendor
      infusion devices was constructed. The system was specifically designed around the
      needs of the critical care environment, and a survey of clinical staff was
      conducted to determine the functional requirements. Hardware, software and system
      configuration was based on the Medical Information Bus IEEE 1073 standard for
      medical device data communications. The infusion devices were configured into
      device communication controllers (DCC), which were polled at 0.25 Hz by a PC
      configured as a bedside communication controller (BCC). The system stores data
      samples after intervals of 1 ml of drug delivery and following any changes in the
      infusion rate. The system demonstrated significant opportunities for supporting
      clinical care and for the management of health care technology.

PMID- 11452635
TI  - Assessment of balanced biphasic defibrillation waveforms in transthoracic atrial
      cardioversion.
AB  - Various electrical pulses have been used for defibrillation. The monophasic
      damped sinusoid waveform, initiated in 60 s, was adopted in virtually all
      defibrillators. Biphasic pulses were introduced recently, achieving success with
      less energy. A biphasic exponential waveform was modelled with 4 ms duration per
      phase with a balanced 3:1 ratio of the first to second phase peak voltages and
      implemented in a defibrillator. A version obtained by chopping the pulses with a
      5 kHz frequency was also used. It was hypothesized that the modelled
      transmembrane voltage decay time is a parameter that could be associated with
      successful defibrillation. The results of cardioversion for two groups of
      patients with the 'classic' monophasic waveform and with the biphasic pulses were
      compared. The mean efficient energy with the damped sinusoid was 205 +/- 85 J,
      versus 88 +/- 43 J with the biphasic pulses, yielding a ratio of 2.32 (1.92 to
      3.2 for fibrillation and flutter, respectively). An acceptable agreement between
      model data and clinical results was found. The transmembrane voltage decay time
      ratios for monophasic versus biphasic pulses was in the approximate range of 2.5
      to 3.5.

PMID- 11452636
TI  - Effect of parameters altering with muscle fibre functional state on power spectra
      of spatially filtered extracellular potentials.
AB  - We aimed to analyse the effect of parameters altered with muscle fibre functional
      state on power spectra (PS) and spectral characteristics of the signals detected
      from skeletal muscle fibres of finite length by bipolar or one-dimensional multi
      electrodes oriented in parallel to the muscle fibres. The PS were calculated as
      the product of the power spectrum of the input signal (the first temporal
      derivative of the intracellular action potential (IAP)) and spatially filtered
      impulse response. A multi-electrode with an even number of poles, located above
      the end-plate or fibre end, reduces the effect of alterations in the propagation
      velocity and increases that of the IAP duration and after-potentials. Detection
      of the signals far from the end-plate and fibre ends reduces the effect of the
      IAP spike duration and increases that of the propagation velocity. Increasing the
      number of poles reduces the effect of after-potentials. A proper multi-electrode
      arrangement and position could help to separate and assess the relative
      alteration of individual parameters.

PMID- 11452637
TI  - The nonlinear dynamical analysis of the EEG in schizophrenia with temporal and
      spatial embedding dimension.
AB  - We applied nonlinear dynamics theory to EEG analysis of schizophrenic patients
      and estimated the correlation dimension with both temporal embedding and spatial
      embedding. A higher D2 was found when using a time-delay embedding method.
      Especially at F7 and Fp1, a significant increase showed. We concluded that more
      complex activity occurred in certain lobes of schizophrenic patients. Using the
      spatial embedding method, a relative lower global correlation dimension was
      obtained. This shows that there might be a diffuse slow wave activity through a
      schizophrene's global cerebrum. Finally, we discuss the study from three angles
      of clinical semiology, spectrum analysis and neuropsychology and draw some
      conclusions about the relationship between the nonlinear analysis of
      schizophrenia EEG and clinical research. It seems that the theory of a nonlinear
      dynamics system is a powerful tool for EEG research and may prove useful in
      complementing visual analysis of EEG accompanied with other study means for brain
      electrical activity.

PMID- 11452638
TI  - Pathways to quality improvement for boarding homes: a Washington State model.
AB  - A quality improvement service delivery model was developed, implemented, and
      evaluated during a boarding home consultation program in Washington State.
      Standardized quality improvement (QI) pathways were utilized to define resident
      issues related to quality of life, quality of care, and safety. The pathways
      assisted boarding homes (n = 126) volunteering for on-site visits with QI
      consultants to identify and address resident needs and meet statutory
      requirements. After 6 months in the program, 78 percent of participating
      residents demonstrated objective clinical improvement. Assisting providers in
      meeting resident needs by using QI pathways will improve residents' quality of
      life, quality of care and safety.

PMID- 11452639
TI  - If improvement of the quality and value of health and health care is the goal,
      why focus on health professional development?
AB  - Connecting organization and issue-centered strategies for the improvement of
      health care with health professional development strategies offers an exciting
      opportunity for the next efforts to improve health care.

PMID- 11452640
TI  - Hospice quality improvement programs: an initial examination.
AB  - Recognizing that little is known about use of quality improvement (QI) processes
      to enhance care of the dying, 11 large hospices exchanged information about their
      QI programs. These hospices reported monitoring from 3 to 50 outcomes measured by
      various indicators and methods. Agencies that related QI to their organization's
      mission, goals, and strategic plan were more likely to have dedicated QI staff; a
      more intense, comprehensive, and participatory QI program; and more QI projects
      resulting in performance enhancement. Both accomplishments and difficulties were
      identified in several areas, including establishing benchmarks, involving staff,
      and using computer technology to manage and analyze QI data.

PMID- 11452641
TI  - Quality measures essential to the transformation of the Veterans Health
      Administration: implications for nurses as co-creators of change.
AB  - Health care systems are changing at an unprecedented rate, but few are making the
      changes in a system affecting nearly 200,000 staff in over 1,100 different sites
      of service delivery originating from 171 medical centers nationwide, as is the
      Veterans Health Administration. The issues of change, quality of care, morale and
      opportunities involved in being a nurse today in a system undergoing this
      magnitude of change is presented within the framework of the quality of care
      initiatives that have been launched by VA. The new organization design of VA,
      emphasizing local decision-making, a description of the multiple quality programs
      recently introduced and integrative strategies that have been used by the Nursing
      Strategic Healthcare Group, the VA corporate level policy and nursing programs
      information center for the country, to support the change process are discussed.

PMID- 11452642
TI  - Maintaining quality care during a nursing shortage using licensed practical
      nurses in acute care.
AB  - Implications of an aging registered nurse workforce, coupled with an inadequate
      supply of new nurses, presented a unique challenge for the nurse executive in an
      acute care hospital. This article presents one possible solution: reintroduction
      of licensed practical nurses to the patient care setting. It describes a pilot
      project initiated to answer the following question: Is there a change in quality
      of patient care or staff satisfaction when the nursing care delivery system adds
      a licensed practical nurse to the registered nurse and patient care assistant
      care pairs? It also describes the driving forces behind this practice change and
      presents focus group discussions, the implementation process, and conclusions and
      recommendations.

PMID- 11452643
TI  - Hospital readmission: predicting the risk.
AB  - This approach focused on identifying specific variables that predict the
      likelihood of readmission. It involved clinical, utilization, and demographic
      variables that are generally available on hospital computer abstract databases.
      The approach included a process for identifying and comparing individual
      variables with the highest risk of readmission. It also contained a procedure for
      assembling risk populations including combinations of variables. The approach
      demonstrated the potential for using risk analysis to maximize the focus of
      clinical management on patient outcomes while reducing the amount of resources
      required for this process.

PMID- 11452644
TI  - Perspectives. Online sales no cure for uninsured, analysts say.

PMID- 11452645
TI  - [Histological variants of thyroid medullary carcinoma].
AB  - A total of 114 medullary carcinomas of the thyroid were studied clinically and
      histologically. Females and subjects aged over 40 years predominated among the
      patients (2-fold more than others). Five- and ten-year survival was 74 and 46.2%,
      respectively. The histological variants were as follows: solid, follicular,
      papillary, small-cell, clear-cell, oncocytic, and mixed medullary-follicular and
      medullary-papillary. The survival of these patients did not depend on the
      histological variant or the degree of tumor cell atypia.

PMID- 11452646
TI  - [Significance of argyrophilic proteins of the nucleolar organizer region in
      differentiation of benign and malignant growth of thyroid epithelial tumors].
AB  - Argyrophilic proteins of nucleolar organizers (NO) were measured in 47 benign (24
      follicular and 8 atypical adenomas) and malignant (8 papillary and 7 follicular
      carcinomas) tumors. The content of argyrophilic NO proteins was significantly
      higher in malignant cells. The proportion of cells with at least 5 silver grains
      per cell was 16.8 and 22.8% in follicular and papillary carcinoma, respectively,
      and 3.2 and 12% in follicular and atypical adenoma, respectively. These data can
      be used as accessory signs in differential diagnosis.

PMID- 11452647
TI  - [Effect of pineal peptides on neuroendocrine system after pinealectomy].
AB  - Removal of the pineal gland leads to structural and functional rearrangement of
      gastric endocrine cells and thyroid C-cells in albino rats, as was shown by
      immunohistological methods and morphometry. Injection of pineal peptides
      epithalone and epithalamine eliminated these changes. Biological activity of
      epithalone is believed to be higher than that of epithalamine.

PMID- 11452648
TI  - [Endocrine glands in alcohol drinkers and patient with alcoholism].
AB  - Chronic alcoholic intoxication results in atrophic and sclerotic changes of the
      endocrine glands, as was demonstrated by 225 autopsies of subjects who suffered
      from heavy drinking (165 cases) and alcoholism (60 cases). Morphometry and
      statistical data processing showed that alcoholism leads to irreversible changes,
      while heavy drinking causes changes that are reversible and compensated. The
      testes and ovaries are the most sensitive to ethanol and acetaldehyde, while the
      adrenals are the least sensitive. The pancreas retains its function for a long
      time despite pronounced changes.

PMID- 11452649
TI  - [Morphological characteristics of placenta and hormonal balance in
      hyperthyroidism of pregnancy].
AB  - Hyperthyroidosis in pregnancy (16 cases) severely alters positive and negative
      correlations between maternal and neonatal thyroid hormones, as well as the
      morphofunctional state of the placenta. Chronic placenta failure (degrees I-II)
      and activation of the structures responsible for additional synthesis of
      placental lactogen results in transplacental passage of thyroxin to the fetus and
      newborn.

PMID- 11452650
TI  - [The role of mitochondrial calcium overload and energy deficiency in pathogenesis
      of arterial hypertension].
AB  - The author proceeds that increased arterial blood (BP) pressure, reflecting the
      shift of the threshold blood pressure controlling system, is conditioned by
      underlying energy deficiency at the cellular level, caused by a decrease of the
      mitochondrial energy generating function. Elevation of systemic BP in
      hyperthyroidism resultant from oxidation-phosphorylation uncoupling, leading to
      decrease of ATP production by mitochondria, is an example of energy dependence of
      the hypertension phenomenon. In primary hypertension (essential hypertension in
      humans and spontaneous hypertension in rats) one can speak about genetically
      determined characteristics of cell membranes (so-called membrane defect) leading
      to insufficient regulation of intracellular calcium and increased concentrations
      of free calcium in the cytosol under physiological actions on cell calcium
      homeostasis mechanisms. Elevation of BP mediated by increased efferent
      sympathetic activity occurs as far as the excess of the cytosolic calcium
      accumulates in the mitochondria and their energy generating function decreases,
      which results in alteration of the ion transporting function of cell membranes.
      Hence, increased systemic BP in primary hypertension should be considered as an
      inherent feature of circulation corresponding to altered cell energetics.

PMID- 11452651
TI  - [Post-infarction heart (pathomorphological criteria for evaluating ventricular
      remodeling)].
AB  - Two hundred and sixty hearts from patients who had died in different periods
      after myocardial infarction (MI) and 40 control hearts were morphologically
      studied. Dilated, hypertrophic, aneurysmal, and endocardial variants of heart
      remodelling after MI are distinguished and their detailed characteristics are
      given. These variants underlie intracardiac hemodynamic changes and
      tanatogenesis.

PMID- 11452652
TI  - [Morphological validation of possibility of transmyocardial laser
      revascularization].
AB  - Serial section of 3 canine hearts were made 2 hours, 8 and 21 days after
      transmyocardial laser vascularization (TMLV). Morphological evidence show it
      possible to develop open transmyocardial channels within 21 days after TMLV if
      they are connected to their intrinsic myocardial vessels.

PMID- 11452653
TI  - [Vascular abnormalities of the spinal cord ].
AB  - Vascular anomalies of the spinal cord were studied in 49 patients. Thirty-three
      cases were morphologically studied (30 cases presented with operative findings
      and 3 cases with autopsy material). The anomalies presented as defects of
      vascular genesis without signs of blastomatous growth (venous and capillary
      venous malformations, arteriovenous anastomose and fistulas, varicosis of the
      spinal cord, etc. located in the spinal cord, its roots, coats, adjacent fat, and
      vertebra which affect the spinal cord, roots or vessels participating in their
      blood supply and venous outflow. In 41% of the cases, the above anomalies were
      associated with congenital anomalies of other systems and organs. The anomalies
      are clinically characterized. Specific signs are given to differentiate them from
      their intracranial analogues. Recommendations are given on pathological
      examination of the content of the vertebral canal in vascular anomalies.

PMID- 11452654
TI  - [Lymphangioleiomyomatosis].
AB  - A case of lymphangioleiomyomatosis of the lungs and lymph nodes of the
      mediastinum and abdomen concurrent with renal angiomyolipomas and leiomyoma of
      the uterus is described. A 24-year-old female died of progressive respiratory and
      cardiac failures caused by proliferation of smooth muscle cells in the bronchi,
      vessel walls and interalveolar septum with the formation of the honey-comb lung.

PMID- 11452655
TI  - [Comparative evaluation of clinical, cytological and cell culture methods of
      candida vulvovaginitis diagnosis].
AB  - 98 patients with Candida vulvovaginitis (CVV) were examined clinically,
      cytologically and culturally. Three clinical forms of CVV were distinguished:
      acute and subacute (26 and 23 patients, respectively)--before treatment, and
      remission (49 patients)--after treatment. The clinical diagnosis of CVV before
      the treatment was confirmed cytologically and/or in cultures (87.7%), in
      remission cytologically (4%), by cultures (20 patients). Candida in the phase of
      budding and pseudomycelium were prevalent in acute CVV (84.4%). In a subacute
      form Candida occurred in 30.3%, while in the remaining cases blastospores were
      observed. Significant correlation between the intensity of Candida colonies
      growth and phase of development on the mucous membrane was not found. Compared to
      the cultural method, the cytological technique is more cost effective, faster and
      simpler.

PMID- 11452656
TI  - [Morphology of the skin manifestations of Lyme disease].
AB  - The paper describes a case of a long-lasting chronic migrant erythema (ME) in an
      82-year-old female, which developed after the bite of an insect (a tick?). The
      specific feature of this case is an unusual duration (2 years) of a single focus
      of ME and autopsy of the skin revealed giant cells with centrally arranged 3-5
      nuclei and cytoplam with PAS-positive inclusions as tiny (5 m) oblong formations,
      that may be Borelia.

PMID- 11452657
TI  - [On the history of foundation of the first society of pathologists in Russia].

PMID- 11452658
TI  - [Pathogenesis of chronic hepatitis C].
AB  - Recent investigations revealed a specific interaction of virus with the host
      immune system. HCV is able to escape and modify the host's immune response,
      notably the rate of production and specificity of rheumatoid factor--the basis
      for mixed cryoglobulins and various non-organospecific and some organ-specific
      autoantibodies. Further studies are required to decode the mechanisms of virus
      host immune system interaction for substantiating the treatment and prevention of
      HCV infection.

PMID- 11452659
TI  - [All-Russian scientific and methodological conference on animal pathology].

PMID- 11452660
TI  - Should nurse-to-patient staffing ratios be mandated by legislation?

PMID- 11452661
TI  - Impact of Genetic potential and prematurity on growth outcomes.
AB  - PURPOSE: To explore the relationship between genetic potential and catch-up
      growth in school-age children who were born prematurely. STUDY DESIGN AND METHOD:
      This descriptive correlational study compared three groups of children who were
      born prematurely, sorted by birthweight groups into low, very low, and extremely
      low birthweight on measures of catch-up growth and body composition at school age
      (n = 45). Height and weight were compared to established norms for children of
      normal birthweight. Growth at school age and parental heights were also
      correlated. RESULTS: Children in all birthweight groups achieved growth within
      normal ranges (two standard deviations from the mean) by school age. The growth
      of the extremely low birthweight group was in the lower range of normal. Maternal
      height was the best predictor of children's heights at 8 to 10 years of age.
      CLINICAL IMPLICATIONS: Parents and providers can be reassured that many children
      overcome the adverse effects of prematurity on childhood growth. Throughout
      childhood, growth should be closely monitored using appropriate grids, and
      correcting for prematurity.

PMID- 11452662
TI  - An integrated approach to prenatal smoking cessation interventions.
AB  - This article encourages the incorporation of smoking cessation activities into
      routine nursing care in the prenatal period. A brief background is given
      regarding the problem of smoking in women--especially pregnant women and
      adolescents. A model is suggested that integrates the Stages of Change framework
      with a program for planning, implementing, and evaluating smoking cessation
      activities in the clinical setting. The use of biochemical testing for cotinine,
      a biomarker of nicotine, is also explored as an evaluation tool and a method of
      self-report confirmation. The nurse is uniquely poised to reduce both the
      healthcare and economic burden of smoking during pregnancy. Because cigarette
      smoking is a major public health problem in the United States today, it is
      important for nurses to have a background in smoking assessment, cessation, and
      evaluation methods. It is critical for all nurses in obstetric, pediatric,
      hospital, and clinic settings to use this knowledge to assist vulnerable clients
      in achieving lifetime abstinence from cigarettes.

PMID- 11452663
TI  - Unique aspects of nursing care for Amish children.
AB  - The purpose of this article is to increase nurses' understanding of the Amish
      culture so nurses can give culturally competent care to Amish children. The Amish
      live in large multigenerational families on farms where hard work is valued;
      worldly conveniences such as electricity, telephones, and automobiles are usually
      shunned. However, the Amish are willing to accept and participate in modern
      healthcare, if its value is clearly understood. Amish beliefs and traditions are
      described, and recommendations for the nursing care of Amish children which are
      consistent with the Amish faith are presented.

PMID- 11452664
TI  - Neonatal circumcision. Benefits, risks, and Family teaching.
AB  - Neonatal circumcision is a frequently performed elective surgical procedure, and
      is one of the oldest known surgical procedures. Neonatal circumcision may be
      performed for medical, cultural, or religious reasons. This article provides
      current information from the literature regarding the risks, benefits, and
      concerns about neonatal circumcision.

PMID- 11452665
TI  - Growth of immigrant Chinese infants in the first year of life.
AB  - PURPOSE: To understand the growth patterns of Chinese-American infants from birth
      to 1 year old. METHODS: Retrospective cohort design comparing the growth patterns
      of 163 Chinese infants living in Ann Arbor, Michigan, and 158 Chinese infants
      living in Taipei, Taiwan. All infants were born at full-term, without major
      medical illnesses. RESULTS: Chinese-American infants were significantly heavier
      and longer than Taiwanese infants for all age groups and for both genders.
      Chinese-American infants were born at average weights, rose to the 70th to 80th
      percentile between 2 and 6 months, and declined to the 50th percentile or less at
      9 to 12 months (when measured by American growth charts). When these infants'
      lengths and weights are plotted on Taiwan's growth curves, no such fluctuations
      were seen. CLINICAL IMPLICATIONS: Our findings suggest that rapid weight gain in
      Chinese-American infants in the first 6 months after birth can be expected, and
      may then lessen. By the first year, on average, these infants' weights will be <
      50th percentile using the American National Center for Health Statistics growth
      standard. These findings can reassure health providers and help them to provide
      sound nutritional recommendations and counselling to parents.

PMID- 11452666
TI  - The postpartum experience for southeast Asian women in the United States.
AB  - PURPOSE: To examine the meaning of postpartum experiences for Southeast Asian
      women living in the United States. STUDY DESIGN AND METHODS: Phenomenology. Open
      ended interviews were conducted with 19 women; audio-taped interviews were
      transcribed and analyzed for recurrent themes. RESULTS: Women identified
      culturally specific treatments they needed to use following the birth of an
      infant. These treatments are meant to delay aging and to prevent chronic
      ailments, and include stringent dietary measures and prolonged rest periods.
      Because childbirth signifies a paramount event in the life of a woman belonging
      to the Cambodian, Vietnamese, or Hmong cultures, she is accorded a great deal of
      assistance from female relatives. Three themes were discovered through this
      research: Prolonged Rest, Regaining Balance in the Body, and the Affiliation of
      Women. The themes give meaning to childbirth experiences and future well-being in
      the community. CLINICAL IMPLICATIONS: The childbirth experience in Southeast
      Asian cultures is saturated with great status, particularly in the family and
      community. In addition, postpartum cultural traditions of Southeast Asian women
      comprise deep meaning for healthy aging. Through this study, nurses can gain a
      more in-depth appreciation of the underlying meanings of postpartum practices for
      Southeast Asian women.

PMID- 11452667
TI  - Kangaroo (skin-to-skin) care with a postpartum woman who felt depressed.
AB  - The mother in this case study had numerous known risk factors for postpartum
      depression and was in rehabilitation for drug abuse. She was crying at 2 hours
      postbirth and expressing feelings of sadness as her baby was being unwrapped for
      her first kangaroo care (KC) experience. Thereafter, during our research
      protocol, her self-reported depression scores decreased rapidly and had
      disappeared by 32 hours postbirth. A benefit of KC requiring systematic study is
      that KC may lessen maternal depression. There is new knowledge that some
      functions of the maternal HPA axis become dampened during the last trimester of
      pregnancy as the placenta increases its secretion of corticotrophin-releasing
      hormone. The sudden loss of the placenta following delivery, accompanied by a
      suppressed HPA axis, may have an effect on mood during the immediate postpartum
      period. Perhaps appropriate reactivation of the maternal HPA axis can be
      triggered following birth by the stimulation inherent in KC, thereby minimizing
      risk for postpartum depression.

PMID- 11452668
TI  - One nurse takes action to prevent infant deaths. Project Moses.

PMID- 11452669
TI  - Pediatric pain discussions on the Internet.

PMID- 11452670
TI  - Nonorganic failure to thrive.

PMID- 11452671
TI  - Nonorganic failure to thrive.

PMID- 11452672
TI  - Fundal pressure.

PMID- 11452673
TI  - Women prisoners.

PMID- 11452674
TI  - Diabetes, statins and cardiovascular disease.

PMID- 11452675
TI  - The health economic impact of antidepressant usage from a payer's perspective: a
      multinational study.
AB  - A multinational decision analytic model was developed to examine the treatment of
      major depressive disorder (MDD) in 10 European and American countries. Input to
      the model was obtained from a meta-analysis of current clinical trial data
      obtained from the published literature, and local clinical and health economic
      experts in each market. The patient- and policy-level impact of MDD treatment was
      measured in each of the 10 markets. The total expected cost per patient for
      treating MDD with venlafaxine XR during the six-month acute phase of MDD was the
      lowest expected cost in nine of the 10 countries studied, resulting in savings to
      the primary payer in almost all markets. As well as the cost savings, the higher
      efficacy and lower rate of dropout found for venlafaxine XR translate to a
      greater number of symptom-free-days (SFDs) per patient. The results of this
      investigation show that use of venlafaxine XR in most settings across Europe and
      the Americas will have a favourable impact on healthcare payer budgets and the
      overall mental health of MDD patients.

PMID- 11452676
TI  - Pravastatin in acute ischaemic syndromes: results of a randomised placebo
      controlled trial.
AB  - Therapy with individual 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (statins) has been shown conclusively to diminish coronary event rates
      and mortality in both primary and secondary prevention. To date, scant attention
      has been paid to whether initiation of such regimens in the hospital phase of
      acute coronary syndromes might confer cardioprotective benefits. The purpose of
      this study was to determine the safety and tolerability of early initiation of
      statin therapy in patients with acute coronary syndromes. In this randomised,
      double-blind, three-month, pilot study, 100 patients with acute myocardial
      infarction or unstable angina and low-density lipoprotein cholesterol > 3.5
      mmol/l were randomly assigned to pravastatin 40 mg daily or placebo initiated
      within 48 hours of hospital admission. Pravastatin proved safe and well tolerated
      in these patients, who were well matched at baseline. No statistically
      significant differences in death, MI and drug-related adverse events were
      observed in the pravastatin group compared with control subjects. This pilot
      study shows that therapy with pravastatin early after an acute coronary event is
      safe and well tolerated. Larger, long-term studies are needed to confirm these
      findings.

PMID- 11452677
TI  - Safety, effectiveness and cost efficacy of diagnostic electrophysiology and
      radiofrequency ablation in a district general hospital.
AB  - Electrophysiological studies (EPS) are now being performed in district general
      hospitals (DGH) in the UK. In order to audit our results, a prospective database
      was established for all patients undergoing EPS and radiofrequency (RF) ablation
      at Eastbourne District General Hospital, East Sussex. Between 1 January 1997 and
      1 July 2000, 300 EPS procedures were performed, resulting in 155 RF ablations.
      The average RF ablation procedure time was 119.3 minutes with an average
      fluoroscopy time of 19.1 minutes. Cost per RF ablation procedure was 1166.79
      Pounds excluding use of facilities, pacemaker devices, medical nursing and
      radiography staffing costs. The overall success rate for RF ablation was 93.6%
      with a major complication rate of 0.6%, a total complication rate of 3.9% and no
      associated mortality. We have shown that RF ablation can be performed safely,
      effectively and economically in a DGH setting with a high rate of success and a
      low complication rate.

PMID- 11452678
TI  - Moxifloxacin versus amoxicillin clavulanate in the treatment of acute maxillary
      sinusitis: a primary care experience.
AB  - In this prospective, multicentre, randomised, non-blinded phase III clinical
      trial, 475 adult patients with acute sinusitis received a 10-day oral regimen of
      either moxifloxacin (400 mg once daily) or amoxicillin clavulanate (875 mg twice
      daily). The primary measure of efficacy was clinical resolution. Secondary
      outcome measures included clinical relapse at follow-up and evaluation of patient
      reported outcomes. Of 471 adults comprising the intent-to-treat population (234
      moxifloxacin, 237 amoxicillin/clavulanate), moxifloxacin treatment was
      statistically equivalent to amoxicillin/clavulanate at the test-of-cure visit
      (85% vs 82%; 95% CI -6%, 13%). Analysis of the efficacy evaluable population,
      confirmed statistical equivalence (86% vs 84%; 95% CI -7%, 13%). Of note, by day
      3 of treatment, significantly more moxifloxacin-treated patients (n = 47; 24%),
      than amoxicillin/clavulanate-treated patients (n = 28; 14%), reported feeling
      better (p < 0.02). Frequency of drug-related adverse events were similar between
      groups: nausea (11% moxifloxacin, 5% amoxicillin/clavulanate) and diarrhoea (3%
      moxifloxacin, 10% amoxicillin clavulanate). In conclusion, once-daily
      moxifloxacin is as effective and safe as twice-daily amoxicillin/clavulanate in
      the treatment of acute sinusitis. Moxifloxacin is associated with more rapid
      symptomatic relief.

PMID- 11452679
TI  - Self-mutilation: review and case study.
AB  - This article reviews in a systematic way the literature on severe self
      mutilation, emphasising possible aetiological factors and warning signs of
      impending self-mutilation. It provides practical advice on the prevention and
      management of such events, including legal issues of capacity and consent. An
      illustrative case history is provided of an artist who cut off his ear.

PMID- 11452680
TI  - Motor restlessness.
AB  - Motor restlessness, characterised by an irresistible urge to move about, can be a
      manifestation of many underlying disorders. Unfortunately, it is often poorly
      recognised and underdiagnosed in clinical practice, possibly because patients do
      not seek medical attention, or their complaints were thought to be secondary to
      anxiety. While the two major conditions to consider are restless legs syndrome
      and neuroleptic-induced akathisia, there are many other differential diagnoses.
      We provide a concise review of the clinical features and diagnostic pitfalls of
      these conditions. A proper detailed clinical history and examination can often
      help clinch the diagnosis, as most of these conditions have their unique clinical
      features.

PMID- 11452681
TI  - Severe bradyarrhythmia in a patient with Alzheimer's disease and a patient with
      cerebral ischaemia, both induced by acute distension of the bladder.
AB  - Two case reports are presented of bradycardia in two elderly patients, which was
      resistant to atropine but which resolved immediately the acute bladder distension
      was treated. Generally, a sympathetic cardiac response is expected, and this
      paradoxical response may be due not only to lesions of the reflex loop involving
      both the vagal and the sympathetic nerves, but also to endocrinological factors.
      As acute urinary distension is not uncommon on geriatric wards, bradyarrhythmia
      due to bladder distension should be considered in elderly patients.

PMID- 11452682
TI  - Xeloda in colorectal cancer.
AB  - Xeloda (capecitabine) is a rationally designed, oral pro-drug of 5-fluorouracil
      (5-FU). It is rapidly and almost completely absorbed in the upper
      gastrointestinal tract. It is then catabolised in a three-enzyme system, the last
      step being catalysed by thymidine phosphorylase, which is upregulated in many
      human cancers. Clinical pharmacology studies have confirmed that this
      preferential activation actually occurs in human colorectal cancer. Phase I and
      II trials were performed in colorectal cancer to define the optimal dose and
      schedule of capecitabine. In two large scale phase III studies this agent has
      been shown to be at least as effective as a standard regimen of bolus 5-FU and
      leucovorin (Mayo regimen). Response was superior in the capecitabine arms of
      these studies with equivalence of progression-free and overall survival. In
      addition the oral regimen was associated with significantly less toxicity. It
      seems likely that this agent will replace intravenous 5-FU in the therapy of
      colorectal cancer and possibly in other cancers.

PMID- 11452683
TI  - Treatment of insomnia with zaleplon, a novel sleep medication.
AB  - Insomnia is a highly prevalent sleep problem that often results in poor daily
      functioning of the affected patient. Unfortunately, sedative hypnotic agents
      prescribed in the past often resulted in residual sedation, as well as impairment
      of cognitive and psychomotor performance, throughout the day after use. Newer
      agents with relatively rapid elimination require administration regularly each
      night before bedtime if symptoms of insomnia are to be prevented and next-day
      sedation is to be avoided. The availability of zaleplon challenges these
      standards of practice. The rapid elimination of zaleplon, combined with its
      unique receptor binding affinity, permits 10 mg of zaleplon to be taken at
      bedtime or later in the night with minimal concern for next-day residual effects.
      Clinical studies of zaleplon also identified the low risk of withdrawal syndrome
      or rebound insomnia after the discontinuation of nightly use. If used only on the
      nights when symptoms actually occur, the occurrence of such problems with
      zaleplon will be minimal.

PMID- 11452684
TI  - A hard thyroid mass due to plasma cell granuloma.
AB  - Plasma cell granuloma involving the thyroid is very rare. A 29-year-old man with
      type 1 diabetes mellitus presented with a one-week history of fever, sore throat,
      neck tenderness and dysphagia. Antibiotics were given but over the next two weeks
      a hard 8 cm mass in the left lobe of the thyroid developed. Fine needle
      aspiration was not diagnostic and surgical exploration revealed an inflammatory
      process arising from the left lobe of the thyroid involving the left
      sternothyroid muscle and parapharyngeal spaces. Histology of multiple biopsies
      showed plasma cell granuloma. Immunoperoxidase staining demonstrated the presence
      of IgG, IgM and IgA with predominance of IgG. The residual mass resolved and was
      impalpable after four weeks. Plasma cell granuloma should be suspected when there
      is a rapidly developing hard thyroid mass. Open biopsy/removal and histological
      confirmation are mandatory and residual disease may resolve within weeks.

PMID- 11452685
TI  - Lymphangioma presenting as a neck mass in the adult.
AB  - Lymphangiomas are uncommon congenital lesions of the lymphatic system which
      usually present in childhood. We report a case of adult lymphangioma, localised
      in the neck, and discuss the presentation, diagnosis and management of this
      tumour.

PMID- 11452686
TI  - Lymphocytic hypophysitis: spontaneous resolution on MRI with progression of
      endocrine defect.
AB  - Lymphocytic hypophysitis is an uncommon condition that typically occurs during
      the last trimester of pregnancy or in the postpartum period. Presentation is of
      an anterior pituitary mass with varying degrees of pituitary dysfunction. We
      present a case in which there was dramatic resolution of the pituitary lesion on
      sequential MRI scanning. Despite this apparent resolution, however, the patient
      continues to have significant pituitary dysfunction.

PMID- 11452687
TI  - Unstable angina following acute MI in a patient with bilateral coronary artery
      fistulae: an unusual presentation of coronary steal?
AB  - We report a 57-year-old woman with acute myocardial infarction and cardiac arrest
      who subsequently developed unstable angina. The possibility of a coronary steal
      syndrome contributing to her unstable angina arises in view of the presence of
      bilateral coronary artery fistulae between two atherosclerotic coronary arteries
      and the main pulmonary artery.

PMID- 11452688
TI  - Avascular necrosis of bone: the hidden risk of glucocorticoids used as
      antiemetics in cancer chemotherapy.
AB  - The role of antiemetics is invaluable in allowing cancer patients to complete
      otherwise potentially intolerable chemotherapy. Corticosteroids have an
      established place in the prevention and treatment of nausea and vomiting due to
      emetogenic cytotoxic agents. Avascular necrosis of bone is a recognised
      complication of glucocorticoid treatment--the risk of this increasing with higher
      doses and longer duration of use. This report details a case of bilateral
      avascular necrosis of the femoral heads in a patient receiving 'standard' doses
      of dexamethasone as part of the antiemetic regimen used in cisplatin-based
      combination chemotherapy.

PMID- 11452689
TI  - Pharmacology and efficacy of eletriptan for the treatment of migraine attacks.

PMID- 11452690
TI  - [Observation of the growth of asthmatic children treated with inhaled steroids].

PMID- 11452691
TI  - [Proposition of using the general index of fluorosis].

PMID- 11452692
TI  - [Validated index of fluorosis in temporal teeth].

PMID- 11452693
TI  - [Sexual violence and related problems in women attending a health care center].
AB  - OBJECTIVE: To estimate the frequency of different forms of sexual violence and
      its association with mental health problems, such as depressive symptoms,
      suicidal ideation and attempt, and alcohol and drug use. MATERIAL AND METHODS:
      From February to March 1998, a cross-sectional study was conducted among 345
      women attending a healthcare center in Mexico City. All women were living with a
      partner/spouse at the time of the study. The proportions of three different types
      of sex life were obtained and compared with the chi-squared test. RESULTS:
      Nineteen per cent of women reported that they had been sexually fondled against
      their will at least once in their lifetime, 11% had been raped, and 5% had been
      forced to touch the sex organs of another person against their will. One in every
      five women reported that they had experienced sexual violence in the context of
      an intimate relationship. An association was found between some forms of sexual
      violence and depression, suicidal ideation, suicide attempts, and use of
      psychoactive drugs. CONCLUSIONS: Sexual violence is a severe public health
      problem that requires implementing specific programs to sensitize and train
      healthcare providers to prevent it.

PMID- 11452694
TI  - [Increasing decayed, missing and filled teeth index among school children in
      Loja, Spain].
AB  - OBJECTIVE: To identify the clinical, socioeconomic, dietary, and hygienic
      predictors of the increasing Decayed, Missing, and Filled Teeth (DMFT) index, in
      a cohort of school children in Loja, Granada, Spain, during a three-year period
      (1994-1997). MATERIAL AND METHODS: A retrospective cohort study was conducted in
      812 students to measure the DMFT index, using the methods recommended by the
      World Health Organization. Statistical analysis was conducted using logistic
      regression models. RESULTS: During the study period, the DMFT index increased
      from 1.86 to 4.5 for the study cohort as a whole, and from 3.71 to 4.47 among
      twelve-year olds. The DMFT at mid-period was associated to an increase in the
      final DMFT. The relative risk for attending school no. 3 was 0.69 (95% CI 0.60
      0.8) vs. school no. 4, and 0.78 (95% CI 0.67-0.90) vs. school no. 5. CONCLUSIONS:
      The final model showed that the DMFT at mid-period was a risk factor for an
      increase in the DMFT index and that attending school number 3 was a protective
      factor.

PMID- 11452695
TI  - [Identification of malignant breast lesions in Mexico].
AB  - OBJECTIVE: To evaluate the modes of detection of breast malignancies in Mexico
      City and to estimate the number of patients diagnosed in advanced stages.
      MATERIAL AND METHODS: This cross-sectional study was conducted between 1994 and
      1996, among 256 women with a histological diagnosis of breast cancer, at three
      tertiary level public hospitals in Mexico City. Personal interviews were
      conducted to collect data on reproductive characteristics, clinical history, and
      breast cancer modes of detection. Data analysis consisted of percentages, odds
      ratios, and 95% confidence intervals. RESULTS: Ninety percent of women sought
      medical care after identifying a breast lump by themselves. Only 10% of patients
      had a stage-I tumor; all 27 cases first identified by a physician were in stage
      II-B and higher. CONCLUSIONS: An increasing trend of breast cancer mortality in
      Mexico City will persist, unless a greater proportion of tumors in situ is
      detected; this would require enhancing breast cancer screening programs and
      conducting an intense educational intervention among women at risk.

PMID- 11452696
TI  - [Correlation of protoporphyrin zinc with lead in blood in workers of the car
      batteries industry in Bogota, Colombia].
AB  - OBJECTIVE: To determine the usefulness of zinc protoporphyrin in blood (PPz) as
      an indicator of lead exposure in workers of the homemade car battery industry.
      MATERIAL AND METHODS: A cross-sectional study was performed in 116 workers of the
      car battery industry in Bogota, Colombia. Data on general, occupational, and
      health variables were collected by interview. Two categories of PPz values were
      established: Those below the cutoff value (70 micrograms/dL) and those above it.
      A linear regression analysis was performed to measure the correlation between
      logarithm values of PPz (> 70 micrograms/dL) and lead in blood (PbB) (> 38
      micrograms/dL). RESULTS: A semi-logarithmic correlation coefficient of r = 0.54
      was found, and statistically significant associations between high levels of PPz
      and direct exposure to lead were observed (OR: 3.35, 95% IC 1.02-11.91; p: 0.02);
      for workers who often use lead as a raw material (OR: 7.80, 95% IC 2.96-21.03; p
      < 0.01), as well as for workers who do not change work clothes often (OR: 3.55,
      95% IC 1.17-11.01; p < 0.01). CONCLUSIONS: PPz may be a useful diagnostic
      indicator for lead poisoning; it may also be used as a screening test for
      surveillance programs in the biological monitoring of workers exposed to lead.

PMID- 11452697
TI  - [An outbreak of Salmonella gastroenteritis among hospital workers].
AB  - OBJECTIVE: To describe and identify the causes of an outbreak of Salmonella
      enteritidis gastroenteritis that took place in June 1998, among tertiary care
      hospital workers, in Mexico City. MATERIAL AND METHODS: Cases were hospital
      workers who developed diarrhea or fever associated with gastrointestinal
      symptoms, after a meal at the hospital's dining room on June eight; controls were
      asymptomatic employees who also ate at the hospital's dining room on the same
      day. A food questionnaire was applied, and stool samples were obtained from all
      study subjects, including kitchen personnel. Blood cultures were practiced for
      febrile patients. Odds ratios with 95% confidence intervals (95% CI) and the chi
      squared were used for statistical analysis. Statistical significance was set at p
      < 0.05. RESULTS: One-hundred-fifty-five workers developed symptoms, but only 129
      (83.2%) answered the questionnaire; 150 controls were also studied. The most
      common symptoms were diarrhea (85%), abdominal pain (84%), cephalea (81.4%),
      nausea (78.3%), and chills (74.4%). Eight blood cultures were negative; 59 stool
      cultures (46%) from cases and six (4%) from controls, were positive for
      Salmonella enteritidis. Egg-covered meat was the suspected source of infection
      (OR 19.39, 95% CI 9.09-41.4); some other foodstuffs like fruit dessert and
      yogurt, were significantly more frequent in cases than in controls. Food cultures
      were all negative. CONCLUSION: This outbreak was probably caused by Salmonella
      contaminated foodstuffs (egg-covered meat with potatoes) due to deficient
      cooking. This report shows the importance of food-quality programs for hospital
      meals.

PMID- 11452698
TI  - [Proposal for a death certificate to improve recording and reporting of perinatal
      mortality].
AB  - OBJECTIVE: To analyze perinatal births and deaths recording at the Mexican
      Institute of Social Security (MISS), and to evaluate the correct classification
      of perinatal deaths. MATERIAL AND METHODS: From January to March 2000, data were
      collected from the 37 MISS districts on the total number of births and deaths
      occurring during 1999, deaths occurring before the seventh day of life, and
      gestational age and weight at birth. Early neonatal and infant mortality rates
      were analyzed including or separating newborns with < 1,000 g and < 28 weeks of
      gestational age. RESULTS: During 1999 there were 634,892 live births--whose
      gestational age and birth weight are unknown- and 3,984 stillbirths > or = 28
      gestation weeks. There were 4,556 newborns who died before the seventh day of
      extrauterine life; 1,385 of them (30.4%) weighted less than 1,000 g and had a
      gestational age < 28 weeks. The analysis of mortality with and without these
      newborns shows a decrease of two points in early neonatal and infant mortality
      rates. CONCLUSIONS: This study shows that classification and reporting of
      perinatal mortality are inappropriate. A proposal is made to develop information
      systems that include weight and gestational age of all births. A new perinatal
      death certificate replacing current fetal and general death certificates would
      allow proper mortality classification and comparisons between countries.

PMID- 11452699
TI  - [Drug supplies in primary care units at the Ministry of Health in Mexico].
AB  - OBJECTIVE: To identify the availability of some essential drugs (ED) at primary
      health care units of the Mexican Ministry of Health (SSA), using data from a
      research work conducted in 1996 and 1997. MATERIALS AND METHODS: A random sample
      of the 18 sanitary jurisdictions of states participating in the Extension of
      Coverage Program (ECP) was drawn. All primary care units from selected
      jurisdictions were evaluated through an inspection visit, using a checklist that
      included 36 ED. In phase I of the analysis, the absolute number and proportion of
      units without a single item of any of the 36 drugs were calculated. In the units
      with available drugs, the median of the distribution was also calculated. In
      phase II, the medians according to the type of health unit and state was
      obtained. The statistic utilized for the comparison of the medians was the
      Scheffe test with one way variance analysis. In addition, the drugs were
      classified according to their therapeutic indication and the medians and
      proportion of available drugs were calculated. The differences in proportion were
      evaluated with the statistic chi 2. RESULTS: During the visits, on average, 18 of
      the 36 drugs included in the list of the study were found in the health units.
      The availability of antibiotics, antituberculosis drugs, and antimalarial drugs
      was particularly poor. In contrast, oral rehydration salts, family planning
      methods and vaccines were usually available. In general, the PAC3 states
      presented the best availability figures. CONCLUSIONS: The Ministry of Health of
      Mexico will have to develop an enormous effort to overcome the obstacles related
      to the supply of essential drugs in primary health care units. Otherwise, all
      other efforts directed to meet the needs of the non-insured population will end
      up being useless, and enormous amounts of the already scarce resources of the
      health sector will be wasted since drugs are a vital component of the long chain
      of health care.

PMID- 11452700
TI  - [Pharmacological therapy compliance in diabetes].
AB  - OBJECTIVE: To establish the frequency of compliance to pharmacological therapy,
      and to identify non-compliance factors, in relation to metabolic control on
      patients with type-II diabetes mellitus. MATERIAL AND METHODS: A comparative
      cross-sectional study was conducted between 1997 and 1998, among 150 type-II
      diabetic patients, at the Family Medicine Unit No. 33, of the Mexican Institute
      of Social Security, in Chihuahua, Mexico. Compliance to drug therapy was measured
      by counting tablets at home. Metabolic control was measured through glycosilated
      hemoglobin. A questionnaire was given to collect data on factors related to
      compliance. Statistical analysis consisted of descriptive statistics, Student's t
      and odds ratios. RESULTS: Pharmacological therapy compliance was 54.2%. Factors
      associated with non-compliance were elementary schooling and lack of information
      about the disease. CONCLUSIONS: Pharmacological therapy compliance was low.
      Factors related to non-compliance can be modified through education.

PMID- 11452701
TI  - Helicobacter pylori: recent advances in the study of its pathogenicity and
      prevention.
AB  - Helicobacter pylori has acquired great importance during the last two decades,
      after being recognized as an important pathogen that infects a great portion of
      the human population. This microorganism is recognized as the main causal agent
      of chronic gastritis and duodenal ulcers, and it is associated with the
      subsequent development of gastric carcinoma. The pathogenic mechanisms of H.
      pylori and their relation to gastric ailments have not been clearly defined.
      However, at present it is well established that urease, vacuolating cytotoxin
      VacA, and the pathogenicity island (cag PAI) gene products, are the main factors
      of virulence of this organism. Thus, individuals infected with strains that
      express these virulence factors probably develop a severe local inflammation that
      may induce the development of peptic ulcer and gastric cancer. The way the
      infection spreads throughout the world suggests the possibility that there are
      multiple pathways of transmission. Due to the importance that H. pylori has
      acquired as a human pathogen, laboratories worldwide are attempting to develop a
      vaccine that confers long-term immunological protection against infection by this
      microorganism. Hence, the objective of this review is to present the most
      relevant findings of the biology of H. Pylori and its interaction with the human
      host.

PMID- 11452702
TI  - P-glycoprotein interactions of nefazodone and trazodone in cell culture.
AB  - This study investigated the effects of nefazodone (NFZ) and trazodone (TZD) on P
      glycoprotein (P-gp) activity and expression in cell culture. NFZ and TZD showed
      no differential transport between the basolateral to apical and apical to
      basolateral direction across Caco-2 cell monolayers. Transport in either
      direction was not affected by verapamil. NFZ was a potent inhibitor (IC50 = 4.7
      microM) of rhodamine123 (Rh123) B to A transport across Caco-2 cell monolayers,
      while TZD had minimal effect. Following 72-hour exposure of LS180V cells to NFZ
      and TZD (10 microM), a twofold increase in immunoreactive P-gp was observed.
      Rh123 accumulation into these cells was reduced to 65% and 74% of control by NFZ
      and TZD (10 microM), respectively. It was concluded that differential rates of
      transport of NFZ and TZD in Caco-2 cells were not evident. However, NFZ is an
      inhibitor of P-gp activity at clinically relevant in vivo concentrations and may
      have the potential to increase bioavailability of coadministered compounds that
      are substrates for transport. Concentrations of NFZ and TZD achieved in the
      intestine after chronic oral dosing may induce P-gp expression and reduce
      absorption of coadministered drugs.

PMID- 11452703
TI  - Effects of oral vitamin K on S- and R-warfarin pharmacokinetics and
      pharmacodynamics: enhanced safety of warfarin as a CYP2C9 probe.
AB  - Evidence for the selectivity of S-warfarin metabolism by CYP2C9 is substantial,
      suggesting that warfarin may be a potential CYP2C9 phenotyping probe. It is,
      however, limited by its ability to elevate the international normalized ratio
      (INR) and potentially cause bleeding. The effect of vitamin K to attenuate the
      elevation of INR may enable the safe use of warfarin as a probe. The objective of
      this study was to investigate the pharmacokinetics and pharmacodynamics of S- and
      R-warfarin in plasma following the administration of warfarin alone versus
      warfarin and vitamin K in CYP2C9*1 homozygotes. Healthy adults received, in a
      randomized crossover fashion in a fasted state, warfarin 10 mg orally or warfarin
      10 mg plus vitamin K 10 mg orally. Blood samples were obtained over 5 days during
      each phase. INR measurements were obtained at baseline and day 2 in each phase.
      INR, AUC0-infinity, and t1/2 of plasma S- and R-warfarin were examined. Eleven
      CYP2C9*1 homozygotes (3 men, 8 women) were enrolled. INR at day 2 following
      warfarin 10 mg was 1.18 +/- 0.19, which differed significantly from baseline (INR
      = 1.00 +/- 0.05) and warfarin with vitamin K (INR = 1.06 +/- 0.07). INR at
      baseline was not significantly different from warfarin with vitamin K. t1/2 and
      AUC0-infinity of both enantiomers did not significantly differ between the
      phases. It was concluded that INR is apparently attenuated by concomitant
      administration of a single dose of vitamin K without affecting the
      pharmacokinetics of either warfarin stereoisomer. Warfarin 10 mg may be safely
      used as a CYP2C9 probe in *1 homozygotes when given concomitantly with 10 mg of
      oral vitamin K.

PMID- 11452704
TI  - Lack of gender differences and large intrasubject variability in cytochrome P450
      activity measured by phenotyping with dextromethorphan.
AB  - Gender-based differences in cytochrome P450 (CYP) activity may occur due to
      endogenous hormonal fluctuations with the menstrual cycle, which are altered by
      oral contraceptives. This study assessed the average activity and within-subject
      variability in CYP3A4 and CYP2D6 in men, women taking Triphasil, and regularly
      menstruating women not receiving oral contraceptives. Thirty-three healthy
      volunteers participated in this 28-day pilot study (12 women receiving Triphasil)
      (OCs), 11 regularly menstruating women not on exogenous progesterone or estrogen
      (no OCs), and 10 men. CYP3A4 and CYP2D6 activities were phenotyped with
      dextromethorphan (DM) on study days 7, 14, 21, and 28 using urinary ratios of
      DM:3-methoxymorphinan (3MM) and DM:dextrorphan (DX), respectively. Serial blood
      concentrations of estrogen and progesterone and menstrual diaries were used to
      determine menstrual phase in both groups of women. Average urinary DM:3MM and
      DM:DX in the 28 extensive metabolizers of CYP2D6 did not differ between the three
      study populations (p = 0.86 and 0.93, respectively). Post hoc power analysis
      indicated that more than 1000 subjects would be needed for 80% power (alpha =
      0.05) to detect a +/- 15% difference from the population mean in the urinary
      ratios of dextromethorphan and its metabolites 3MM and DX. Variability in CYP3A4
      and CYP2D6 activity, characterized by intrasubject standard deviation, also did
      not differ. The varying doses of levonorgesterol and ethinyl estradiol in
      Triphasil, fluctuations in estrogen and progesterone, and menstrual phase did not
      influence CYP3A4 or CYP2D6 activity. It was concluded that CYP3A4 and CYP2D6
      activity and intrasubject variability were not different in the three study
      populations, and thus a clinically important difference between men, women on
      Triphasil, and women not receiving oral contraceptives is unlikely. High inter-
      and intrasubject variability in DM:3MM and DM:DX were clearly demonstrated and
      limit the use of dextromethorphan to phenotype endogenous CYP3A4 and CYP2D6
      activity.

PMID- 11452705
TI  - Pharmacokinetics of zidovudine and lamivudine in neonates following
      coadministration of oral doses every 12 hours.
AB  - A phase I, repeat-dose, open-label study was conducted to determine the
      pharmacokinetics and safety of zidovudine and lamivudine, coadministered orally
      every 12 hours, in 16 neonates whose mothers were infected with human
      immunodeficiency virus type 1 (HIV-1). The prospective mothers had been
      stabilized on a zidovudine/lamivudine regimen since week 36 of pregnancy to
      prevent mother-to-child transmission of HIV. During 1 week postpartum, the
      mothers received zidovudine 300 mg plus lamivudine 150 mg every 12 hours and
      breastfed. Neonatal treatment was initiated 12 hours following birth with 4 mg/kg
      of zidovudine suspension plus 2 mg/kg of lamivudine solution every 12 hours; this
      regimen was continued for 1 week. Between days 1 and 7 of neonatal treatment, the
      neonatal oral clearance (CL/F) of zidovudine and lamivudine increased by 2-fold
      (p < 0.001) and 1.6-fold (p = 0.004), respectively, possibly reflecting
      maturation of intestinal hepatic and renal function occurring during the first
      week of life. Day 7/day 1 ratios for exposure (area under the serum concentration
      time curve [AUC]) and maximum observed serum concentration (Cmax) were 0.48 and
      0.63, respectively, for zidovudine and 0.64 and 0.73, respectively, for
      lamivudine. At the time of delivery, the geometric mean cord/maternal
      concentration ratio was 1.24 for zidovudine and 1.12 for lamivudine, indicating
      free passage of each drug across the placenta. The maternal and neonatal
      treatment regimens were well tolerated. The results of this study confirm that in
      the neonate, a convenient regimen combining zidovudine 4 mg/kg and lamivudine 2
      mg/kg, administered orally every 12 hours, provides zidovudine serum exposure
      very similar to that reported with the standard neonatal zidovudine regimen of 2
      mg/kg every 6 hours, as well as lamivudine serum exposure within the range
      reported in adults receiving lamivudine 150 mg twice a day and children receiving
      4 mg/kg twice a day.

PMID- 11452706
TI  - The pharmacokinetics of irbesartan in hypertensive children and adolescents.
AB  - An open-label study was conducted to characterize the pharmacokinetics and
      antihypertensive response to irbesartan in children (1-12 years) and adolescents
      (13-16 years) with hypertension. Patients received single once-daily oral doses
      of irbesartan 2 mg/kg (maximum of 150 mg once daily) for 2 to 4 weeks (+/-
      nifedipine or hydrochlorothiazide). Plasma irbesartan concentrations were
      determined by a validated high-performance liquid chromatography/fluorescence
      method from blood samples taken predose, up to 24 hours after dosing on Day 1,
      and up to 48 hours after the final dose. The plasma concentration-time profiles
      were similar between the 6- to 12-year and the 13- to 16-year age groups and to
      that previously determined from a study of adult subjects receiving approximately
      2 mg/kg (i.e., 150 mg) oral irbesartan once daily. Mean reductions in
      systolic/diastolic blood pressure were 16/10 mmHg at Day 28 with irbesartan
      monotherapy (n = 8). Irbesartan was well tolerated and may be a treatment option
      for pediatric hypertensive patients.

PMID- 11452707
TI  - Acid-suppressive therapy use associated with antihypertensive agents.
AB  - Nitrates and calcium channel blockers (CCBs) have been shown to decrease lower
      esophageal sphincter pressure and theoretically may precipitate or aggravate
      gastroesophageal reflux. Thus, the authors hypothesized that patients who receive
      these agents would have greater use of acid-suppressive drug use, defined as
      histamine2 antagonists or proton pump inhibitors. A retrospective cohort design
      was used to assess the use of acid-suppressive drug use in hypertensive patients
      with respect to both nitrates and antihypertensive therapy. Of 15,662 treated
      hypertensive patients, 20% received acid-suppressive therapy. An increased use of
      acid-suppressive therapy was associated with nitrate (odds ratio [OR] = 1.71),
      CCB (OR = 1.46), and alpha 1 antagonist (OR = 1.32) treatment, which appeared to
      be additive when patients received two or more of the agents. Within the class of
      CCBs, there was no significant difference among the individual agents. As the
      clinical and economic burden may be substantial, further study is warranted.

PMID- 11452708
TI  - Population pharmacokinetics of fentanyl in healthy volunteers.
AB  - The authors compared the population pharmacokinetics of fentanyl using a standard
      individualized modeling (SIM) approach versus that of a nonparametric expectation
      maximization (NPEM) approach. The pharmacokinetic properties of fentanyl
      administered as a single 5 ug/kg intravenous infusion were evaluated in 18
      healthy volunteers by use of SIM as well as with NPEM. NPEM-derived parameters
      were a total body clearance of 2.12 +/- 0.28 L/kg/h, distributional clearance of
      8.43 +/- 4.58 L/kg/h, central volume of distribution of 1.22 +/- 0.21 L/kg, and
      peripheral volume of distribution of 1.81 +/- 1.47 L/kg. Identified parameter
      values from the modeling methods resulted in virtually identical simulated
      profiles; this finding was confirmed when median values noted were not
      statistically significantly different between modeling methods (SIM or NPEM).
      However, the NPEM algorithm uniquely identified a greater distributional
      clearance in the elderly population and also illustrated a profile with at least
      10% of the study population having a very high clearance of fentanyl. This
      finding may affect the therapeutic use of fentanyl. NPEM allows for a more
      informative global representation of a drug's pharmacokinetics.

PMID- 11452709
TI  - Effect of age and gender on the safety, tolerability, and pharmacokinetics of BAY
      12-9566 in healthy subjects.
AB  - The impact of age and gender on the single-dose pharmacokinetics, safety, and
      tolerability of BAY 12-9566 was evaluated in healthy subjects. Volunteers were
      grouped according to age and gender (13 young males, 11 elderly males, and 12
      elderly females) and then randomized in a 2:1 ratio to receive a single oral 50
      mg dose of BAY 12-9566 or placebo. Serial plasma samples were collected up to 336
      hours postdose and assayed for BAY 12-9566. Peak plasma concentration, time to
      reach peak plasma concentration, the area under the concentration-time curve,
      oral clearance, volume of distribution, and elimination half-life were
      calculated. BAY 12-9566 was well tolerated in all treatment groups, and no
      serious adverse events occurred during the study. Substantial age- or gender
      related differences were not observed for any of the pharmacokinetic parameters
      tested. Based on these pharmacokinetic and tolerability profiles, age- or gender
      related dose adjustments were not required for BAY 12-9566.

PMID- 11452710
TI  - Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking
      status and gender.
AB  - Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid
      for adults. Since smoking often begins in adolescence, we determined the single
      dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13
      to 18 years old. Subjects self-reported their smoking status. Urinary cotinine
      concentration was used to verify smoking status. Thirty-seven subjects (18 males,
      19 females) were classified as cigarette smokers and 38 were nonsmokers (19
      males, 19 females). Fasted subjects received one tablet (150 mg) of bupropion SR,
      and plasma samples were collected before (0) and 1/2, 1, 2, 3, 4, 6, 8, 24, 48,
      and 72 hours after dosing. Plasma samples were analyzed for bupropion and its
      three major metabolites (hydroxybupropion and the aminoalcohol isomers,
      erythrohydrobupropion plus threohydrobupropion, expressed as a composite) by
      solid-phase extraction, followed by LC/MS/MS. Factorial analysis of variance
      (ANOVA) was used to evaluate the effects of smoking and gender on pharmacokinetic
      parameters. Smokers and nonsmokers differed significantly (p < 0.05) in age and
      urinary cotinine (p < 0.01) concentration but did not differ significantly in
      mean weight, height, body surface area, or body mass index. The pharmacokinetic
      (PK) parameters for bupropion and hydroxybupropion did not differ between smokers
      and nonsmokers, but differences were found between male and female subjects. Mean
      values for area under the plasma concentration versus time curve (AUC0-
      >infinity), volume of distribution (Vd beta) normalized to body weight, maximum
      plasma concentration (Cmax), and elimination half-life (t1/2 beta) for bupropion
      were significantly (p < 0.05) greater in females than males, while clearance of
      bupropion normalized to body weight (CL/f) did not differ between males and
      females. Females also exhibited significantly (p < 0.05) larger values for
      hydroxybupropion mean AUC0-->infinity and Cmax than males. The mean ratio of
      hydroxybupropion to bupropion AUC for adolescents was approximately 4 to 5, which
      is lower than that previously reported for adults. In conclusion, smoking status
      does not affect the single-dose pharmacokinetics of bupropion SR in adolescents.
      However, females differ from males in several potentially important PK parameters
      for bupropion and its major metabolite, hydroxybupropion.

PMID- 11452711
TI  - The effects of converting from simvastatin to atorvastatin on plasminogen
      activator inhibitor type-1.
AB  - Plasminogen activator inhibitor type-1 (PAI-1) is an important regulatory
      component of fibrinolysis and is elevated in the presence of endothelial
      dysfunction. Endothelial dysfunction and PAI-1 in patients with coronary artery
      disease (CAD) have been demonstrated to improve following simvastatin therapy.
      The effect of converting from simvastatin to atorvastatin on PAI-1 has not been
      reported and may be an additional consideration when making a formulary
      medication switch. Fourteen adult patients with hypercholesterolemia and CAD who
      were receiving simvastatin for a minimum of 3 months were randomized to continue
      on simvastatin or be converted to atorvastatin. Doses were adjusted to achieve or
      sustain a low-density lipoprotein (LDL) cholesterol of < or = 100 mg/dL. A
      fasting lipid panel and PAI-1 were obtained at baseline and following 10 weeks of
      treatment. Mean +/- SD LDL cholesterol at baseline (95.6 +/- 13.8 vs. 87.0 +/-
      12.3 dL, p = 0.24) and following 10 weeks of simvastatin or atorvastatin (96.6 +/
      8.9 vs. 87.4 +/- 20.3 mg/dL, p = 0.29) were similar. No differences in PAI-1
      were observed at baseline (47.7 +/- 19.3 vs. 64.6 +/- 22.2 ng/mL, p = 0.15) or at
      10 weeks (51.1 +/- 32.5 vs. 63.9 +/- 26.9 ng/mL, p = 0.44). These data suggest
      that the conversion from simvastatin to atorvastatin does not adversely affect
      PAI-1 plasma concentrations in patients with CAD.

PMID- 11452712
TI  - Pharmacokinetics of buspirone extended-release tablets: a single-dose study.
AB  - The objective of this study is to evaluate the absorption of buspirone and its
      biotransformation to 1-(2-pyrimidinyl) piperazine (1-PP) from two different
      extended-release (ER) formulations of buspirone HCl tablets (12-hour and 24-hour
      in vitro release) and from a commercially available immediate-release (IR)
      tablet. A single dose of the 30 mg ER tablets was compared with two doses of the
      15 mg IR tablet administered 12 hours apart. Eighteen healthy male subjects
      participated in this randomized, open-label, three-treatment crossover study.
      Blood samples were obtained at 22 time points from predose (0 hour) until 36
      hours postdose, and plasma concentration of buspirone and 1-PP was determined by
      LC/tandem mass spectrometry method. The pharmacokinetic parameters AUC0-t, AUC0
      infinity, Cmax, tmax, Ke, and t1/2 were calculated and statistically analyzed.
      The results indicated extended release of buspirone from the two test products in
      vivo with a 70% to 90% greater bioavailability in comparison with the IR
      formulation. The bioavailability of 1-PP from ER formulations appears to be equal
      to that from the IR formulation. Both buspirone ER tablets successfully delivered
      bioavailable buspirone with a reduction in peak drug and metabolite plasma
      levels, prolonged buspirone plasma concentrations, and decreased ratio of 1-PP to
      buspirone concentration with less intersubject variation when evaluated as a
      single-dose study in healthy human subjects.

PMID- 11452713
TI  - Measurement of tumor response using [18F]-2-fluoro-2-deoxy-D-glucose and positron
      emission tomography.

PMID- 11452714
TI  - Positron-emission tomography tracers as intellectual property.

PMID- 11452715
TI  - The molecular imaging branch of NIMH: PET and SPECT tracers.

PMID- 11452716
TI  - Licensing and distribution of research tools: National Institutes of Health
      perspective.

PMID- 11452717
TI  - The patenting of tools for drug discovery and development.

PMID- 11452718
TI  - Neuroimaging consortium workshop: development of novel PET and SPECT ligands for
      brain imaging.
AB  - It was clear from the levels of participation in this panel discussion and from
      the levels of interest expressed in the upcoming NIMH tracer Consortium Workshop
      that there is a great deal of potential benefit to public health from the
      development of new PET and SPECT (and, perhaps, MRI?) tracers. For extramural NIH
      programs, the tool guidelines for grantees are in fact only that--guidelines--but
      they could become specific regulations if unacceptable threats to basic research
      are perceived. This is because the benefits of collaboration among basic
      scientists are considered essential for the success of research programs. On the
      other hand, intramural programs at NIH are considered by some to be the "beta
      test site" for emerging issues and policies, regardless of the specific
      scientific topic. This may well be true for research tools and presents an
      opportunity to find new ways of working. As for the industry, threats to
      intellectual property arise from myriad sources. The magnitude of these threats
      can only be appreciated from the perspective of long-term investment in research
      based industries with significant regulation. In particular, the pharmaceutical
      industry enjoys only a relatively short period of time during which investments
      in the last medicament can be recouped to support the development of the next. A
      great deal of commitment and sophistication will be required if the United States
      shall succeed in finding new ways of translating basic into applied science for
      the practical benefit of currently underserved patient populations.

PMID- 11452719
TI  - The use of imaging as biomarkers in drug development: regulatory issues
      worldwide.

PMID- 11452720
TI  - Submission of images to the center for biologics evaluation and research in
      support of license applications for therapeutic agents.
AB  - CBER's philosophy partners with the sponsor's philosophy in the development of
      electronic dossiers. Based on the experience gained from a number of dossiers,
      CBER has established a standard management paradigm and imaging platform by which
      the review of radiographs has been facilitated.

PMID- 11452721
TI  - Can [15O]water be used to evaluate drugs?
AB  - There is an extensive literature supporting the use of rCBF as a surrogate marker
      of local neuronal activity. This provides a strong physiologic rationale for
      using PET measurements of rCBF to study the effects of drugs acting on the brain.
      The ability to perform multiple brief measurements of rCBF with [15O]water in a
      single study session makes possible a wide variety of experimental designs.
      Numerous investigators have successfully applied the method to study a wide
      variety of centrally acting drugs. In summary, then, the answer to the question,
      "Can [15O]water be used to evaluate drugs?" is a definitive yes.

PMID- 11452722
TI  - Regulation of the production and use of radiopharmaceuticals in Germany and
      Europe.

PMID- 11452723
TI  - Regulatory aspects of nuclear imaging in neuropharmacology.

PMID- 11452724
TI  - Nonimaging detectors in drug development and approval.
AB  - Regulatory applications for imaging biomarkers will expand in proportion to the
      validation of specific parameters as they apply to individual questions in the
      management of disease. This validation is likely to be applicable only to a
      particular class of drug or a single mechanism of action. Awareness among the
      world's regulatory authorities of the potential for these emerging technologies
      is high, but so is the cost to the sponsor (including the logistics of including
      images in a dossier), and therefore the pharmaceutical industry must evaluate
      carefully the potential benefit of each technology for its drug development
      programs, just as the authorities must consider carefully the extent to which the
      method is valid for the use to which the applicant has put it. For well
      characterized tracer systems, it may be possible to design inexpensive cameras
      that make rapid assessments.

PMID- 11452725
TI  - Prospects for human pharmacological functional magnetic resonance imaging
      (phMRI).

PMID- 11452726
TI  - Reversal of multidrug resistance with LY335979: functional analysis of P
      glycoprotein-mediated transport activity and its modulation in vivo.

PMID- 11452727
TI  - 99mTc-tetrofosmin for functional imaging of P-glycoprotein modulation in vivo.
AB  - Tetrofosmin is a widely available and conveniently prepared tracer that has been
      shown to be a transport substrate for Pgp and MRP in vitro and in vivo. Its
      properties are similar but not identical to those of sestamibi. The available
      data suggest that clinical studies involving imaging of MDR function and in vivo
      modulation of MDR function could be performed with tetrofosmin or sestamibi, but
      the two should probably not be used interchangeably.

PMID- 11452728
TI  - P-glycoprotein at the blood-brain barrier and analysis of drug transport with
      positron-emission tomography.

PMID- 11452729
TI  - Nuclear imaging and biomarkers in drug development using approved
      radiopharmaceuticals.

PMID- 11452730
TI  - The use of microPET for the development of neural repair therapeutics: studies in
      epilepsy and lesion models.

PMID- 11452731
TI  - Neuroimaging and drug development: an algorithm for decision making.

PMID- 11452732
TI  - Monitoring disease progression in Parkinson's disease.

PMID- 11452733
TI  - The 2000 Alfred P. Wolf Award.

PMID- 11452734
TI  - Immunological and molecular analysis of the sentinel lymph node: a potential
      approach to predict outcome, tailor therapy, and optimize parameters for tumor
      vaccine development.

PMID- 11452735
TI  - Serotonin 5-HT1A receptor imaging in the human brain with positron-emission
      tomography: coordination and the standardization and dissemination of
      methodology.

PMID- 11452736
TI  - Imaging cellular proliferation as a measure of response to therapy.
AB  - Cell proliferation imaging is based on extensive laboratory investigations of
      labeled thymidine being selectively incorporated into DNA. [11C]-Thymidine
      labeled in the ring-2 or the methyl position is the natural extension of earlier
      work using tritiated thymidine. Proliferation imaging using [11C]-thymidine
      requires correction for labeled metabolites; however, quantitative approaches can
      provide reliable estimates of cellular proliferation by measuring thymidine flux
      from the blood into DNA in tumors. 18F-labeled thymidine analogs that are
      resistant to catabolism in vivo, [18F]-FLT and [18F]-FMAU, may simplify
      quantitative analysis and may be more suitable for clinical studies but will
      require careful validation to determine how their uptake is quantitatively
      related to cell growth. Clinical studies using [11C]-thymidine have demonstrated
      the power of cellular proliferation imaging to characterize tumors and monitor
      response early in the course of therapy. Patient imaging using the PET thymidine
      analogs is at an earlier stage but appears promising as a clinically feasible
      approach to cellular proliferation imaging.

PMID- 11452737
TI  - 18FDG for the study of central nervous system drugs.

PMID- 11452738
TI  - [Legionella sp.--laboratory diagnosis of infections in humans and detection in
      environmental water].
AB  - Legionella sp. is the etiological agent of Legionnaires Disease and the Pontiac
      Fever, one of the new emerging diseases. Legionella are common in natural
      environment but in low number of bacteria cells, especially in comparison to
      other bacterial flora. Because of special nutritious requirement and long time of
      Legionella generation, the isolation of bacteria and the diagnosis of
      legionellosis cause many problems. In this publication some methods for detection
      of Legionella sp. in environmental water and clinical samples are presented and
      evaluated.

PMID- 11452739
TI  - [The effect of tannery waste products on viability of selected bacteria from
      activated sludge].
AB  - In this study we have investigated the influence of sludge on the activity of
      bacteria strains: Acinetobacter baumannii, Aeromonas hydrophila and Pseudomonas
      cepacia. To our studies we have taken waste materials used in the chromium
      compound leather tanning process as well as materials from leather fat and waste
      materials, in general. It was confirmed that 1:20 dilution of chromium tanning
      leather waste, retanage and leather fat allowed the survivability of bacteria in
      all three strains. Through our research we were able to establish that general
      sewage with a decreased level of chromium practically did not effect the
      survivability of bacteria in a sewage environment. Both types of waste, city
      sewage as well as leather waste, were shown not to facilitate bacterial growth.
      If chromium waste flow into city sewage without treatment, bacteria can only
      survive at a dilution level of 1:20, which will not affect the survivability of
      bacteria used in biological waste treatment.

PMID- 11452740
TI  - [Correlations between mutagenicity of airborne particles and concentrations of
      air pollutants].
AB  - With highly efficient aspirometry method there were sampled airborne particles in
      different parts of Wroclaw in winter and summer. Organic compounds adsorbed on
      the particles were extracted for 8 hours in Soxhlet apparatus. Concentration of
      PAHs and benzo(a)pyrene was determined with GC-MS. Mutagenicity of particles was
      examined with Ames test. Concentrations of airborne particles ranged from 17-144
      mg/m3, and organic compounds adsorbed on the particles--1.1-28.6 mg/m3.
      Concentrations of PAHs from EPA list ranged from 8.3-1211.6 ng/m3,
      benzo(a)pyrene's ones--from 4.5-709 ng/m3. Airborne particles sampled in many
      different locations of Wroclaw in winter and summer displayed mutagenic activity.
      Air volumes polluted with the particles resulting in mutagenic effect in Ames
      test in TA 98 strain without activation with fraction S9 ranged from 0.25-42.5
      m3. They displayed correlation with concentration of airborne particles
      (correlation index -0.35), organic compounds adsorbed on the particles
      (correlation index -0.58), PAHs from EPA list (correlation index -0.52) and
      benzo(a)pyrene (correlation index -0.52). Physiochemical indexes of air pollution
      only approximately indicate health hazards caused by mutagenes and cancergenes
      adsorbed on airborne particles. Therefore monitoring of air pollution should be
      supplemented with testing their mutagenicity with Ames test.

PMID- 11452741
TI  - [Plasticity of memory in the brain of white rats after long-term exposure to
      titanium in drinking water].
AB  - The experiment was conducted on male white rats from breeding base of the
      National Institute of Hygiene: WIS own breeding. During sixteen months the
      drinking water with TiCl3 in concentrations 5 and 25 mg/l, what is equivalent
      respectively 0.45 and 2.25 mg per 1 kg of daily weight of rats, was given the
      animals. After 3 and 15 months of exposure the rats were taught to differentiate
      and remember sight effects. The investigation of each cluster of rats, living
      previously in the same cage, was going non-stop by 24 hours for 5 days. The
      training was carried on in the special adopted cages making possible to record
      all correct and incorrect attempts in day long cycle. Percentage indicator, the
      ratio of mistakes to all number of the attempts, was used for assessment the
      training effectiveness in each group and the result in intoxicated group were
      compared with control group. During the whole time of exposition the supplying
      drinking water with TiCl3 in concentrations 5 and 25 mg/l has not caused changes
      in rats confirming possibility to evoke disorders of brain memory plasticity.

PMID- 11452742
TI  - [Functioning biological activity of mean mineralized sodium bicarbonate in water
      from the "Pitoniakowka" source in Szczawnica, designed for health resort potable
      cures].
AB  - In the experiments on animals the biological activity of the water from its
      intake "Pitoniakowka" (outflow B + C + D + G) in Szczawnica has been determined.
      The basic investigations were carried out on rats whom in the course of 24 days
      the investigated water was being administered to drink ad libitum or by probe in
      a single daily dose of 10.7 ml/kg of body weight. It has been ascertained that
      the water caused a statistically significant increase of the concentration of
      sodium and a fall of the levels of potassium, magnesium, calcium, total
      cholesterol, the HDL fraction of cholesterol, total lipids in the blood serum,
      also of hematocrit, hemoglobin and erythrocytes. The investigated water inhibited
      the motor activity of the small intestine of the rabbit, caused increased
      urination and increased water turnover in the organism. A long-lasting
      application of the investigated water may lead to the genesis of metabolic
      acidosis. There was not observed any cholagonic and any chologenic activity of
      the investigated water in guinea pigs or any effect of that water on the elements
      of the carbohydrate metabolism, the protein metabolism or on the peripheral blood
      smear in rats.

PMID- 11452743
TI  - [Formaldehyde emissions from wooden products and office furniture].
AB  - The formaldehyde emission from wood-products (particleboards, particleboards
      veneered with artificial veneer, laminated particleboard, hard fibreboards,
      plywood) and office furniture was measured with the use of environmental chamber
      (0.2 m3, 0.6 m3, 1.0 m3 capacity) in the following conditions: temperature 23
      degrees C, relative humidity 45%, 1 air exchange/hour and factor loading 1 m2/m3.
      Formaldehyde was determined by using colorimetric methods. Among the tested
      products, hard fibreboards, plywood and almost all of the enriched particleboards
      should not contaminate indoor air with formaldehyde over its threshold limit
      values. The tested office furniture fulfill of the hygienic requirements.

PMID- 11452744
TI  - [Organochlorine insecticides of women's milk in Olsztyn in 1976, 1986, 1996].
AB  - Residual amounts of organochlorine insecticides: gamma-HCH, DDT and its
      metabolites DDE and DDD were determined by gas chromatography in human milk
      collected in Olsztyn in 1996. The results were compared with the results obtained
      earlier in 1976 and 1986 in the same region of Poland. It was observed that with
      time the amount of chlorinated hydrocarbons tended to decline. The residual
      amount of sigma DDT in 1996 was 8 times lower than in 1986 and 19 times lower
      than in 1976. On the other hand, the amount of gamma-HCH in 1996 was 7 times
      lower than in 1986 and 41 times lower than in 1976. Although the quantity of
      sigma DDT decreases with time, it still exceeds considerably the Maximum Residue
      Levels of these compounds in baby food.

PMID- 11452745
TI  - [Evaluation of theoretical accuracy, reliability, discriminative power and
      difficulty for physical, mental and social well-being scales in adolescents].
AB  - The purpose of this study was to develop and validate the questionnaire used to
      measure adolescents' wellbeing and its physical, mental and social dimensions.
      The questionnaire was composed of two parts: the first part contained wellbeing
      indicators and the second part contained criterion indicators (health disorders
      and harmful behaviours). Physical wellbeing scale contained the most common
      complaints due to psychosocial and life style factors, and was measured by three
      indicators: headache, abdominal pain and backache. Mental wellbeing scale
      contained emotional and moral dimensions that were recognised as closely
      connected with the physical disorders from one hands and the process of
      socialisation from the other hands. There were eight indicators: fatigue, stress,
      fear, depression, loneliness, helplessness, feeling of guilt, and low self
      complacency. Five indicators: perceived social support, relationship with mother,
      father, friends and teacher measured social wellbeing scale. Each indicator of
      wellbeing is scored in three scales: dichotomise scale, five-point Likert scale
      and visual analogue scale. The cluster sample of 445 schoolchildren aged 14-15
      years, randomly selected from the last grade of elementary schools of Warsaw was
      surveyed in October-November 1999. The physical, mental, social and total
      wellbeing scales were found to be reliable, but differing in internal
      consistency. The total and mental scales of wellbeing demonstrated high
      reliability, while the physical and social scales demonstrated moderate
      reliability. Analysis of correlation between criterion and tested variables
      showed acceptable discriminative power of the physical, mental, social and total
      wellbeing scales. Respondents assessed the five-point Likert scale as easier in
      comparison to dichotomise and visual analogue scales.

PMID- 11452746
TI  - The influence of food consumption level on body growth of school children (7-10
      years old) in Egypt.
AB  - The nutritional status of children (7-10 years old) depends to great extent on
      the type of food they eat. The natural growth of children is considered as an
      indicator of their nutritional status in addition to that children are considered
      the building blocks of healthy societies. This paper presents the results of
      questionnaire studies of nutrition of school children in Egypt with the special
      emphasis given to social-economic status in the families. The results show the
      effect on nutritional status on body growth of school children (7-10 years old)
      in Egypt and relationship between difference social-economic level in the
      families.

PMID- 11452747
TI  - The dental prosthesis used for intraoral muscle therapy in the rehabilitation of
      the stroke patient. A preliminary research study.
AB  - The dentist can maximize the oral rehabilitation of the stroke patient's weak or
      paralyzed oral musculature, resulting in dysfunctional speech, swallowing and
      deglutition, with the use of palatal lift and palatal augmentation prostheses.
      The study described here evaluates functional changes using these prostheses for
      three post-stroke patients with left hemiparesis. Clinical tests indicated
      decreased nasal emission and hypernasality, and improved speech articulation.
      Videofluoroscopy evaluation showed improvement in the oral phase of swallowing.
      Patient self-assessment indicated improved satisfaction with treatment.

PMID- 11452748
TI  - Cervicofacial subcutaneous emphysema after lower root canal therapy.
AB  - Subcutaneous emphysema can occur when high-speed, air-cooled, rotary cutting
      instruments are used near open wounds and introduce air into subcutaneous or
      facial spaces of the face and neck. The case reported here describes an episode
      of cervicofacial subcutaneous emphysema after lower tooth root canal therapy.

PMID- 11452749
TI  - A rare encounter.

PMID- 11452750
TI  - Ergonomic considerations for the care of special patients.
AB  - Ergonomics is an applied science concerned with the design of products that
      improve the way in which people and technology interface. The applications to
      dentistry are numerous given the fact that modern dental care is a complex blend
      of human skills and sophisticated technology. This article explores the impact of
      ergonomic principles on dental care for the special and physically challenged
      patient.

PMID- 11452751
TI  - A severed finger for a "very bad toothache".

PMID- 11452752
TI  - My expert's better than your expert.

PMID- 11452753
TI  - Don't forget the roots.

PMID- 11452754
TI  - Third-party payors. A mixed blessing.

PMID- 11452755
TI  - Case of the month. Hepatic and renal failure in a patient taking troglitazone and
      metformin.
AB  - Troglitazone is a thiazolidinedione with insulin-sensitizing activities when
      administered to humans or animals with type 2 diabetes mellitus. It has been
      shown to have numerous desirable metabolic effects on glucose and lipid
      metabolism. A major adverse effect of troglitazone is the development of
      hepatotoxicity. In early clinical trials, elevations of serum aminotransferases
      (> 3 times upper normal limit) occurred in 48 of 2510 (1.9%) subjects receiving
      troglitazone. In December 1997 and again in August 1998, the United States Food
      and Drug Administration issued stronger warnings after getting reports of more
      than a hundred cases of liver damage, including liver failure requiring
      transplantation in three patients and death in another patient. Warner-Lambert
      Company announced on March 21, 2000 that it is voluntarily discontinuing the sale
      of Rezulin (troglitazone) tablets for the treatment of type 2 diabetes. Media
      reports sensationalizing the risks, associated with Rezulin therapy had created
      an environment in which patients and physicians were simply unable to make well
      informed decisions regarding the safety and efficacy of Rezulin. Under these
      circumstances, and after discussions with the FDA, the company decided it was in
      the best interests of patients to discontinue marketing Rezulin. Concerns about
      the hepatotoxicity of troglitazone led the Medicine Control Agency of the United
      Kingdom to request voluntary withdrawal of the drug from the UK in December 1997.

PMID- 11452756
TI  - Antibiotic resistance.

PMID- 11452757
TI  - Common urologic problems in children: guides to evaluation and referral, Part II.
AB  - A discussion of common urologic problems in children is presented to provide
      primary physicians with appropriate guidelines for evaluation and referrals. The
      problems will be discussed in two parts: Part I covered urinary tract infections,
      voiding dysfunctions, hematuria, and proteinuria. Part II will cover
      abnormalities found on antenatal renal ultrasonography, hypospadias and other
      penile anomalies, phimosis, undescended testes, inguinal hernia and hydroceles,
      and varicoceles. An adage states: "The questions in medicine never change over
      time--only the answers." Certainly the busy primary care physician may experience
      the frustration of changing evaluation guidelines established by narrow
      subspecialties. Guidelines for the evaluation of children with disorders of the
      genitourinary tract are no exception. The following presentation will address
      some of the most common childhood urologic problems with a brief discussion of
      how to evaluate and when to refer for pediatric urologic consultation or
      management.

PMID- 11452758
TI  - Purified protein derivative (PPD) tuberculin skin testing of patients with HIV
      infection.

PMID- 11452760
TI  - The good, the bad and the ugly.

PMID- 11452759
TI  - The case for oversight.

PMID- 11452761
TI  - [Preventive analgesia: a new trend in anesthesiology. An idea born and developed
      at the P.A. Herzen Institute of Oncology].
AB  - The authors summarize positive experience gained in the use of preventive
      anesthesia in oncosurgery. The new trend in anesthesiology has been developed at
      P. A. Herzen Institute of Oncology since the end of the eighties. A peripheral
      analgesic (aspisol, ketoprofene, ketorolac, etc.) was added to traditional
      premedication and anesthesia protocols in 522 patients subjected to extensive
      cavitary and other than cavitary surgery. Hemodynamic and metabolic parameters,
      homeostasis, stress criteria (hydrocortisone and glucose), pain intensity
      according to the verbal evaluation scale were studied at all stages of anesthesia
      and postoperative period, and side effects of postoperative analgesia were
      analyzed. Use of nonsteroid antiinflammatory drugs before the intervention and in
      the postoperative period prevented the development of strong postoperative pain
      and notably decreased the need in opioid analgesics in the presence of stable
      homeostasis. No serious side effects of analgesics, including hemorrhagic
      complications, were observed.

PMID- 11452762
TI  - [Remifentanyl: pharmacokinetics, pharmacodynamics, use].

PMID- 11452763
TI  - [Early post-anesthesia adaptation: review of the problem].

PMID- 11452764
TI  - [Inflammatory reaction and sepsis in pancreatic necrosis].
AB  - Analysis of clinical data, results of treatment, and the development of systemic
      inflammatory reaction (SIR) in 100 patients with sterile or infective
      pancreonecrosis and pancreatogenic necrosis demonstrated a phase-wise pattern in
      the development of inflammatory and septic process in pancreonecrosis. The
      development of inflammation and sepsis in such patients is determined by the
      extent of involvement, infection of necrotic zone, and disease duration. SIR,
      shock, and polyorgan failure are the cardinal components in the pathogenesis of
      various phases of pancreonecrosis. Detection of signs of SIR and sepsis are
      needed for individual and urgent evaluation of patient's state. The scale for
      evaluating the severity of patient's physiological condition and index of
      involvement of abdominal and retroperitoneal organs are the most accurate,
      sensitive, and quantitative characteristics for evaluating the patient's
      condition and the course and outcome in pancreonecrosis.

PMID- 11452765
TI  - [Prevention of disorders of myocardial contractile function in patients with
      ischemic heart disease during aortocoronary shunting].
AB  - The efficacy of pre-, intra-, and postoperative prevention of hemodynamic
      disorders by creatinine phosphate, cytochrome C, and glutamic acid was evaluated
      in 61 coronary patients with decreased myocardial contractility. All these agents
      exerted a positive inotropic effect in coronary patients with ejection fraction
      below 0.4, increasing the stroke volume and left-ventricular ejection fraction
      without modifying heart rate. Glutamic acid is not recommended for preoperative
      treatment, because it increases oxygen consumption by the myocardium above the
      reserve potential of the coronary bed. Cytochrome C is the most effective drug
      for preoperative treatment. Intraoperative preischemic protection of the
      myocardium by cytochrome C in coronary patients during high risk operations
      prevents the development of unfavorable hemodynamic complications during
      induction and maintenance of anesthesia before artificial circulation, provides
      favorable recovery of cardiac activity, decreases the incidence of severe
      arrhythmias, promotes a rapid and full-value recovery of myocardial contractile
      function after ischemia, and decreases the incidence of acute heart failure.

PMID- 11452766
TI  - [Problems and advances in anesthesiology and intensive care in oncologic
      surgery].
AB  - Numerous problems are to be solved by anesthesiology and reanimatology in modern
      oncosurgery: to protect weak exhausted patients from severe and extremely severe
      surgical injury, to carry out rational infusion/transfusion therapy and intensive
      care in massive blood loss, perioperative organ and polyorgan failure, and
      sepsis. Combined analgesia is used in highly traumatic oncological operations:
      inhalation narcosis with fluorine drugs with epidural analgesia and anesthesia.
      Good results were obtained in the treatment of very grave patients. Mortality
      from highly traumatic operations with blood loss higher than 50% of total
      circulating blood decreased to 10%. Modern methods of intensive care, such as
      intraoperative reinfusion of autoerythrocytes, extracorporeal detoxication,
      immunocorrection for preventing and treating sepsis, etc., are widely used with
      good effect.

PMID- 11452767
TI  - [First experience with clinical use of intravenous anesthetic recofol:
      effectiveness and safety].
AB  - Clinical trials of a new anesthetic Recofol were carried out. This analog of well
      known drug diprivan is characterized by a predominantly hypnotic effect. The
      effect of recofol on hemodynamics, gas exchange, and EEG was studied in 30
      clinical trials during anesthesia for bronchoscopic manipulations and operations
      on the abdominal and thoracic organs, microsurgery, and during peripheral vessel
      repair. The results indicate that recofol is virtually identical to diprivan
      (propofol). Clinical course of induction and anesthesia, hemodynamic reactions
      and effect on the respiratory system of patients were virtually the same. Recofol
      was well tolerated, its allergenic activity was relatively low, it was rapidly
      metabolized, there were virtually no side effects. Positive results of recofol
      trials carried out by Leiras Oy firm recommend the drug for wide use in
      anesthesiology.

PMID- 11452768
TI  - [Neuroanesthesiology: past, present and future].

PMID- 11452769
TI  - [Sevoflurane inhalation anesthesia for short surgical interventions].
AB  - Sevoflurane, a new halogen inhalation anesthetic for mononarcosis, was used in 33
      patients aged 22-57 years subjected to noncavitary general surgical and
      urological operations lasting for 50 +/- 9 min. Induction anesthesia consisted in
      sevoflurane inhalation in a semi-open contour. The anesthetic was delivered first
      in a dose of 0.2 vol% which was increased to 3-4 vol% by the end of induction
      (1.5-1.8 MAC). Laryngeal mask was used in 28 patients, in the rest tracheal
      intubation was carried out after succinyl choline. Maintenance dose of
      sevoflurane was 2-3 vol%. Electrocardiogram was recorded and arterial pressure
      monitored by indirect methods, pulse oxymetry and capnography were carried out.
      For evaluating the probable toxic effect, serum levels of total bilirubin, SGPT,
      creatinine, alkaline phosphatase, urea, albumin, potassium, and sodium were
      measured. Sevoflurane did not suppress the respiration and allowed assisted
      ventilation of the lungs, if necessary. No appreciable changes in the
      hemodynamics were observed, though heart rate was to be monitored. There were no
      biochemical shifts indicative of hepatic or renal involvement. Sevoflurane is
      recommended for total anesthesia in short non-cavitary interventions as
      mononarcosis, that is, such anesthesia requires virtually no extra narcotics,
      neuroleptics, or ataractics.

PMID- 11452770
TI  - [Total intravenous anesthesia with propofol, fentanyl and clopheline in young
      children with occlusive hydrocephalus during ventriculoperitoneal shunting].
AB  - Total intravenous anesthesia with propofol, fentanyl, and clonidine was used in
      infants aged under 1 year operated on for occlusive hydrocephalus. The course of
      anesthesia in 18 patients with the hypertensive hydrocephalus syndrome is
      analyzed. Four of these patients with an extremely grave premorbid history and
      body weight of 1-3 kg were operated on before the age of 2 months. Propofol can
      be used in infants aged under 1 year, including physiologically immature small
      for-date infants. Clonidine, an alpha 2-adrenoagonist, used in older
      neurosurgical patients and adults for stabilizing cerebral perfusion pressure, is
      allowed in infants, too. The authors analyze the time course of central
      hemodynamics during anesthesia with propofol, fentanyl, and clonidine and
      anesthesia by other drugs (combined anesthesia with ketamine and opioid
      analgesics, neuroleptanalgesia).

PMID- 11452771
TI  - [Clinical and experimental study of xenon anesthesia].
AB  - Narcotic effect of inert gas xenon (Xe) was discovered more than 50 years ago.
      The main causes limiting its clinical application are high price, low
      availability (in nature the gas is present in scarce amounts), and absence of
      preclinical trials sufficient for norm-setting documents and further solutions
      allowing clinical trials of Xe. Results of original and basic clinical and
      experimental studies of xenon anesthesia are presented. The studies were carried
      out by a group of authors in accordance with the requirements and norm-setting
      documents of Pharmacological Committee of Ministry of Health of the Russian
      Federation, needed for permitting Xe for medical application as a new narcotic
      agent.

PMID- 11452772
TI  - [Choice of components of general anesthesia in patients with concomitant
      fibrillation arrhythmia in surgery on organs of the abdominal cavity].
AB  - The central hemodynamic parameters were studied in 45 patients with ciliary
      arrhythmia operated on the abdominal and pelvic organs under different
      anesthesia. Epidural anesthesia as a component of total anesthesia had a
      favorable impact on the hemodynamics of such patients, decreasing the heart rate,
      mean arterial pressure, and oxygen consumption by the myocardium; the authors
      emphasize a high efficacy of blocking the pituitary-adrenal stressor stimulation
      in combined anesthesia.

PMID- 11452773
TI  - [Combined intravenous and epidural anesthesia in laparoscopic surgery].
AB  - Two methods of anesthesia (total intravenous and combined intravenous + epidural)
      are compared in patients after laparoscopic cholecystectomy with grave
      concomitant diseases of the circulatory and respiratory systems. Combined
      anesthesia should be preferred in this category of patients.

PMID- 11452774
TI  - [Clinical toxicology on the threshold of the 21st century].
AB  - Progress in clinical toxicology implies search for new approaches to improving
      the intensity of urgent detoxication in patients with acute poisoning by
      stimulating the natural cleansing of the organism, improving complex detoxication
      as part of adsorption, dialysis filtration, apheretic, and physiohemotherapeutic
      procedures, and creation of new specific (antidote) drugs). Progress in clinical
      diagnosis requires further research of new types of acute poisoning and the
      endotoxicosis syndrome and development of information and consultation service
      for such cases.

PMID- 11452775
TI  - [Ketoprofen (ketonal): a drug for preventing and treating postoperative pain].
AB  - A prophylactic approach to the management of postoperative pain is described:
      ketoprofen, a nonsteroid antiinflammatory drug, was used, which possesses
      numerous advantages and a variety of dosage forms. To cancer patients subjected
      to extensive radical operations on the pelvic organs, head, and neck, ketonal
      (ketoprofen) was injected intramuscularly or rectally in a dose of 100 mg 1 h
      before surgery and in a daily dose of 300 mg during the postoperative period.
      Adequate postoperative monoanalgesia with ketonal was attained in 47% patients.
      In the rest patients ketonal was combined with medium-potent opioid tramadol. A
      more potent opioid buprenorfin (sangesik) in the minimal daily dose of 0.3 mg was
      required in only 2 cases. Nonsteroid antiinflammatory drug ketoprofen (ketonal)
      in therapeutic doses administered preventively before surgery intramuscularly or
      rectally notably decreased the acuity of the postoperative pain syndrome.

PMID- 11452776
TI  - [Heart conduction system under conditions of general anesthesia. Results of a 15
      year study].
AB  - Effects of 14 anesthetics, narcotic analgesics, benzodiazepines, and their
      combinations on the cardiac conduction system (CCS) were studied in 470 surgical
      patients of a general profile during operation and narcosis by transesophageal
      electrocardiostimulation. Interactions between components of total anesthesia can
      improve or suppress the intracardiac conduction. The authors classified the data
      on the effects of agents used for narcosis on the sinus node function and
      atrioventricular and anteretrograde conduction. The results will help an
      anesthesiologist in a differentiated approach to the choice of anesthetics for
      surgical patients with initially disordered CCS and heart rhythm.

PMID- 11452777
TI  - [Digestive enzyme activity in the small intestine of the rat offspring from
      mothers subjected low protein diet during pregnancy or lactation].

PMID- 11452778
TI  - [Ranges of regulation of sodium, potassium, calcium, magnesium levels in plasma,
      erythrocytes, and muscle tissues of Rutilus rutilus in natural conditions].

PMID- 11452779
TI  - [Cyclonucleotide-dependent pathway--one of the mechanisms of olfactory
      transduction of the amino acid signal in Cyprinus carpio].

PMID- 11452780
TI  - [Effects of glucose, insulin, and adrenaline on feeding behavior in fishes].

PMID- 11452781
TI  - [Development of the cardioelectric field on the body surface during activation of
      the ventricular myocardium in the Callus domesticus hen].

PMID- 11452782
TI  - [Effect of dexamethasone on the rat respiratory passages].

PMID- 11452783
TI  - [Parameters of the adrenal cortex hormonal function and its modification during
      the rat development].

PMID- 11452784
TI  - [Pretectal and tectal connections in the turtle intergeniculate leaflet detected
      by a trace method].

PMID- 11452785
TI  - [Catecholamines in the regulation of the functional state of vasopressinergic
      cells in the rat hypothalamus].

PMID- 11452786
TI  - [Morphological basis of development of hemato-liquor barrier of the choroid
      plexus in prenatal ontogenesis].

PMID- 11452787
TI  - [Changes in erythrocyte properties in early postnatal ontogenesis in rats].

PMID- 11452788
TI  - [Duration of the estrous cycle as a factor for species conservation].

PMID- 11452789
TI  - [Properties of gluconeogenesis enzymes from flatworms].

PMID- 11452790
TI  - [Acyl pocket of the active center in cholinesterases and dialkyl phosphates: a
      study of their interaction by statistical methods].

PMID- 11452791
TI  - [Hemodynamics and activation of mechanoreceptors in the human carotid sinus].
AB  - Investigation into consequences of the carotid sinus stimulation has revealed
      that the stimulation elicited a considerable decrease in arterial blood pressure
      because of a decrease in the cardiac output (often) or in peripheral vascular
      resistance (less frequently). The type of the response to the stimulation was
      found to depend on haemodynamic characteristics at rest.

PMID- 11452792
TI  - [Urokinase stimulates whereas tissue plasminogen activator attenuates blood
      vessel stenosis].
AB  - Periadventitial application of the urokinase-plasminogen activator (uPA) in
      pluronic gel to an injured artery stimulated the neointima and neoadventitia
      formation as well as cell migration and proliferation in vivo. In contrast, the
      tissue-type plasminogen activator (tPA) reduced the number of neointimal smooth
      muscle cells and neointimal area and attenuated the lumen stenosis after a
      balloon catheter injury of the rat carotid artery. This ability to stimulate the
      neointima and neoadbentitia formation was found to be quite specific for the uPA.
      The findings suggest that this uPA property provides a specific functional target
      for attenuating growth of the damage.

PMID- 11452793
TI  - [Oxidative stress in pathogenesis of arterial hypertension in ISIAH rats].
AB  - The NO-synthase activity and the rate of NO production in the rat aortic wall and
      cerebellum were 2-1.5-fold higher in the ISIAH rats than in normotensive WAG rat
      strain. In contrast, the superoxide dismutase (SOD) activity was significantly
      reduced in the ISIAH rats. The blood level of reduced thiols was also much lower
      in the ISIAH rats. The findings suggest that oxidative stress may play a
      significant role in pathogenesis of stress-sensitive hypertension in the ISIAH
      rat strain.

PMID- 11452794
TI  - [Functional organization of lymphatic microvessels of the rat mesentery].
AB  - Lymph flow as measured with biomicroscopic and speckle-interferometrical
      techniques was very unstable and its rate did not depend on lymphangion diameter
      in the rat mesentery. A correlation was found between amount of cells in the
      lymph flow and other indices of lymphangion functions. All microvessels with
      phasic contractions and/or working valve were revealed as having a lymph flow.
      The phasic activity and the valve work correlated with each other. The higher the
      amplitude and frequency of the phasic activity and the longer the contraction
      cycle, the higher was the rate of the valve work.

PMID- 11452795
TI  - [Neurogenic contractions of the rat tail artery under isobaric conditions: effect
      of transmural pressure and function of the endothelium].
AB  - In stimulation of the rat nerve with a modulated sine pattern, an increase in the
      modulating frequency from 0.03 to 0.15 Hz diminished the latency between the
      stimulating signals and changes in the vessel resistance as well as the amplitude
      of the flow oscillations, but did not affect tonic contractions of the vessel. A
      reduction of transmural pressure from 80 to 40 mm Hg increased both the tonic and
      the phasic components of the vessel contraction. Following the endothelium
      removal no change in the response latency occurred. The data obtained suggest
      that, during a rhythmic neurogenic influence, the vascular endothelium may work
      as an "amplifier" of the vessel's phasic contractions.

PMID- 11452796
TI  - [Reflection of distribution of the epicardial ventricular potential on the dog
      body surface during electrical stimulation of the myocardium].
AB  - Electrical pacing of the apex, base, and free wall of the heart right and left
      ventricles, as well as the left ventricle's interventricular septum revealed that
      localisation of the ectopic focus determined the sequence of ventricular
      depolarisation, the site formation, and the pathway of displacement of the areas'
      positive and negative potentials and their extrema on the thoracic surface. Time
      of the mutual movement (inversion) of positive and negative zones on the body
      surface was found to depend on the pacing site in the wall of ventricles.

PMID- 11452797
TI  - [The role of mu- and delta-opiate receptors in resistance of the myocardium to
      free radical damage].
AB  - I.v. administration of the delta-opioid (OR) receptors' agonists DSLET or DTLET
      prevented creatine kinase leakage from the rat isolated heart in oxidative stress
      damage and abolished an increase in myocardial levels of conjugated diens and
      malondialdehyde. The agonists also prevented a stress-induced augmentation of the
      superoxide dismutase (SOD) activity. All protective effects of delta-receptor
      stimulation was completely abolished by the delta OR antagonist ICI 174,864. The
      data obtained suggest that the cardioprotective effect of the delta OR
      stimulation in vivo is not mediated via direct cardiac delta OR activation but,
      probably, rather via some unknown indirect circulating humoral factor(s).

PMID- 11452798
TI  - [I/D polymorphism in the angiotensin-converting enzyme gene in men with
      myocardial infarction at young age].
AB  - The rate of D allele did not differ between patients with ischemic heart disease
      (IHD) who had myocardial infarction before the age 45, and healthy males. The DD
      genotype of the ACE gene was much more frequently encountered in the patients
      than in healthy males. The findings suggest that the DD genotype is an
      independent risk factor of the IHD and myocardial infarction in young patients.

PMID- 11452799
TI  - [Effect of stimulation of mu-opiate receptors on contractility of the isolated
      heart in normal oxygenation and during ischemia-reperfusion].
AB  - Activation of mu-opioid receptor (OR) in rats prevented development of
      reperfusion-induced myocardial cell damage. In contrast, direct cardiac mu-OR
      stimulation with the opioid receptor agonist DAMGO decreased cardiac
      contractility in normal oxygenation and aggravated the reperfusion-induced
      myocardial cell damage. The findings suggest that the cardioprotective effect of
      mu-OR stimulation is not mediated via cardiac mu-OR activation.

PMID- 11452800
TI  - [Effect of He-Ne laser irradiation on the functional activity of smooth muscle
      cells in the portal vein].
AB  - Irradiation of the rat portal vein's fragments with the He-Ne laser for 3, 5 and
      10 minutes reduced the fragments tone by half. Frequency of phasic and tonic
      contractions did not change, their amplitude, however, increased by neatly 40% as
      compared with the initial level. The NO synthase blocker N-nitro-L-arginine
      administered prior to the irradiation had no effect on the above parameters. The
      data obtained suggest that the decrease of the vessel tone is due to production
      of the EDRF and cGMP. The increase in the amplitude of phasic and tonic
      contractions of the vein's smooth muscle cells is associated with an increased
      Ca++ entry in each contraction cycle.

PMID- 11452801
TI  - [Effect of marinobufagenin on the primary reinforcing effect of ethanol].
AB  - Intraperitoneal administration of marinobufagenin resulted in a reliable and dose
      dependent suppression of ethanol self-administration in drug- and experimentally
      naive DBA/2 mice. The findings suggest that Na/K-ATPase contributes to both
      mediation of the ethanol reinforcing properties and the mood regulation.

PMID- 11452802
TI  - [The constant level of the right atrial pressure and its role in the venous
      return characteristics].
AB  - Dynamics of the central venous pressure, superior and inferior v. cava flow and
      venous return following action of pressor stimuli were studied in acute
      experiments on anaesthetised mongrel cats with artificial lung ventilation and
      opened chest. The central venous pressure returned to the initial level faster as
      compared with the dynamics of superior and inferior v. cava flow and venous
      return. The superior v. cava blood flow increased more than that of inferior v.
      cava. The data suggest that the central venous pressure is controlled near the
      lower constant level.

PMID- 11452803
TI  - [Trigger activity of ryanodine in mechanism of cholinergic atrial fibrillation in
      dogs].
AB  - Systemic infusion of ryanodine did not prevent induction of atrial fibrillation
      (AF) during acetylcholine (Ach) perfusion in frogs. The AF, however, appeared
      later as of the dogs/Ach perfusion start and lasted for a shorter time as
      compared with the control. The activation mapping of the right atrium showed no
      significant difference from the control. The findings suggest that the mechanism
      of AF induction is hardly related to triggering activity, at least in this
      particular model.

PMID- 11452804
TI  - [Myocardial ischemic preconditioning: pathophysiological mechanisms and prospects
      of clinical application (a literature review)].
AB  - Ischemic preconditioning (IPC, i.e. increase in the organ resistance to a
      prolonged ischemia which occurs after a brief ischemic challenge) seems to be one
      of the most powerful endogenous cardioprotective mechanisms known to date.
      Current data regarding molecular mechanisms of early (classic) IPC as well as the
      second window of protection are reviewed in the context of the concept of
      sequential three-staged development of protective effect. Based on original and
      published data, possible mechanisms of remote IPC are considered. The review
      comprises current ideas of existence of the IPC clinical correlates and its use
      in clinic.

PMID- 11452805
TI  - [Life and fate of professor I. F. Tsion].

PMID- 11452806
TI  - A little magic works wonders.

PMID- 11452807
TI  - Easing into the night. A program that meets the special needs of the evening
      tour.

PMID- 11452808
TI  - Effective design. "Idealized design" focuses on the relationships withan
      organization.

PMID- 11452809
TI  - A virtual community of caregivers. Online access to caregiving information.

PMID- 11452810
TI  - What we know is not enough.

PMID- 11452811
TI  - Focus on resident value. Achieve success one senior at a time.

PMID- 11452812
TI  - Laparoscopic pancreatic resection.
AB  - The extent of reported laparoscopic resections vary from enucleation to
      pancreaticoduodenectomy. Although initial series have been reported with
      encouraging results, most patients with pancreatic disease requiring resection
      are still treated with an open approach. We present a review of our experience
      and of the world literature on laparoscopic pancreatic resection. Laparoscopic
      pancreaticoduodenectomy has been attempted in 12 patients with a conversion rate
      of 33%. Complications occurred in the laparoscopic group. The laparoscopic
      patients have experienced no benefit in the postoperative recovery and
      convalescence. Early experience with the hand-assisted approach is promising.
      Sixty-eight laparoscopic distal pancreatectomies and enucleations have been
      reported to date. They were 42 distal pancreatectomies and 26 enucleations.
      Thirteen procedures have been converted to open surgery (19.1%). There was no
      mortality and the main postoperative complication was pancreatic leak (5
      patients, 7.3%). Average hospital stay was 9 days. These results compare
      favorably with the outcomes after open pancreatic resection. While laparoscopic
      pancreaticoduodenectomy is not associated with patient benefit and may be
      accompanied by increased morbidity, laparoscopic distal pancreatectomy and
      enucleation are safe, carry low morbidity and have encouraging results in terms
      of postoperative recovery.

PMID- 11452813
TI  - [Significance of video-assisted thoracoscopic surgery in the diagnosis and
      staging of primary pulmonary neoplasms].
AB  - The authors describe the usefulness of video-assisted thoracoscopic surgery
      (VATS) in the staging and diagnosis of primary lung cancer. In the Oncological
      Thoracic Surgery Department of Milan's National Cancer Institute, over the period
      from January 1995 to January 2000, 46 patients, suspected of having mediastinal
      lymphadenopathies in the presence of lung cancer, were proposed for a VATS
      biopsy. Forty-four patients underwent a thoracoscopic lymph node biopsy (95%),
      while in 2 subjects, in whom pleural metastases were found, the histological
      diagnosis was established by pleural metastatic nodule thoracoscopic biopsy (5%).
      A VATS lymph node biopsy was performed in 16 cases at level 5 (35%), in 13 at
      level 6 (28%), in 9 at level 7 (19%) and in 6 at level 8 (13%). Lymph node
      biopsies were ipsilateral in 37 patients (80%) and contralateral in 7 (15%). No
      postoperative complications were observed. Histological examination revealed
      adenocarcinoma in 23 cases (50%), epidermoid carcinoma in 12 (26%), microcytoma
      in 8 (17%) and giant-cell lung carcinoma in 3 (7%). Two patients were classified
      as stage IV (5%), 7 as stage III B (15%) and 21 as stage III A (45%). The
      subsequent treatment was neoadjuvant chemotherapy for stage III A patients and
      chemotherapy in association with radiotherapy for stage III B subjects. The
      patients with microcytoma underwent integrated radiotherapy and chemotherapy and
      pan-encephalic radiotherapy. Sixteen patients, with negative frozen-section
      histological findings for mediastinal lymph node neoplastic disease, underwent
      pulmonary resection after thoracotomy in the same operating session (35%) and
      were subsequently classified as stages I and II. In conclusion, VATS proved
      extremely useful in the diagnosis and staging of patients affected by lung cancer
      with synchronous lymph node enlargement. This procedure allowed the diagnosis of
      suspect involved mediastinal lymph nodes in all cases thus affected and the
      exclusion of lymph node disease in patients subsequently treated by lung
      resection in a single session. The precise staging obtained then made it possible
      to direct the patients towards the most appropriate form of treatment.

PMID- 11452814
TI  - [Non-palpable lesions of the breast: retrospective clinical study].
AB  - A non-palpable breast lesion (NPBL) is a disease of the mammary gland that cannot
      be detected during clinical examination but that can be visualized by mammography
      and/or ultrasonography, either during screening programs or sometimes in
      asymptomatic women. These small lesions require an adequate diagnostic
      therapeutic approach to ensure correct treatment. The aim of the present study
      was to analyse a series of NPBLs retrospectively in order to define them
      nosologically and establish an adequate diagnostic-therapeutic work-up for such
      cases. Ninety-three patients with a total of 99 NPBLs were observed from January
      1989 to December 1999. The 99 NPBLs were submitted to ultrasonography and 31
      (31.3%) were also submitted to US-guided fine needle aspiration biopsy (FNAB).
      Later on the diagnostic-therapeutic procedure involved surgical biopsy after
      radiological centering and, in the case of malignant neoplastic lesions, surgical
      intervention and adjuvant therapy. Ultrasonography confirmed the presence of NPBL
      in 45 cases of the 99 detected at mammography (45.4%). Cytological examination of
      the 31 FNABs yielded the following results: unreliable 19.3%, suspected
      malignancy 42%, negative for neoplastic cytology 6.5%, positive for carcinoma
      32.3%. The histological diagnosis was one of mammary carcinoma in 41 patients
      (43%). Among the 41 carcinomas there were 8 (19.5%) carcinomas in situ, 24
      (58.5%) invasive ductal carcinomas, 8 (19.5%) invasive lobular carcinomas, and 1
      (2.5%) medullary carcinoma. In the 32 (80%) patients submitted to lymphadenectomy
      for 33 invasive carcinomas, 6 patients (18.7%) presented positive lymph nodes
      (N1). The Authors conclude that NPBLs are an important clinical entity because
      they may be the expression of a malignant lesion; most NPBLs are diagnosed during
      screening programs or sometimes in asymptomatic women by means of mammography,
      which is the only standardised method for their identification. The poor
      diagnostic capability of non-invasive methods and the potential malignancy of
      NPBL justify the indication for surgical excisional biopsies; in cases of
      histological findings of malignancy it is often possible to perform conservative
      surgery with similar results to radical surgery in terms of survival. When NPBLs
      turn out to be invasive carcinomas, a concomitant lymphadenectomy is mandatory.

PMID- 11452815
TI  - [General anesthesia and cervical anesthesia. What changes in carotid surgery].
AB  - Carotid surgery must be preventive; therefore cerebral protection procedures have
      been the centre of interest for a decade. Nowadays local cervical block
      anaesthesia seems to have changed the terms of the problem allowing achieve the
      aim of "no risk surgery". Therefore we considered our 16 year experience (352
      carotids operated on 290 patients). Since 1990 we employed cervical block
      anaesthesia. In order to ratify as much as possible the two groups of comparison,
      considering that we adopted some exclusion criteria, we compared the results of
      the first hundred carotids that underwent surgery with general anaesthesia and
      the first hundred operated using cervical block anaesthesia. Since we adopted
      cervical block anaesthesia there was no need of intra-operative monitoring
      systems because we considered exclusively the patients' clinical answer to
      preclamping. The use of shunt decreased from 9% to 3%. Surgery performed in
      cervical block anaesthesia gives a positive impression. This is due to the fact
      that there is not only a significant reduction of the morbidity rate, especially
      from a neurologic point of view, but also a reduction of the post-operation
      hospital stay. Furthermore there is also a better organization of the surgical
      phases. Direct monitoring of the cerebral function allows a precise analysis of
      the peri-operatory neurological events. In conclusion our study suggests that
      cervical block anaesthesia allows clinical benefits for the patient as far as
      safety is concerned being also more convenient under the economic point of view.

PMID- 11452816
TI  - [Central segmental pancreatectomy in benign and borderline neoplasms of the
      pancreatic isthmus and body].
AB  - We report our experience with middle segment pancreatectomy for benign, cystic
      and borderline tumours of the neck and body of the pancreas. The guidelines for
      management of these tumours are unclear. Formerly they were usually resected with
      a pancreatico-duodenectomy or distal pancreatectomy including the spleen.
      However, such operations may cause high morbidity, a notable wastage of normal
      tissue and an unnecessary risk of diabetes mellitus and splenic loss. Four
      patients (age range: 34-72 years) with tumours of the neck or body of the
      pancreas underwent a middle segmental pancreatectomy. The cephalic stump was
      sutured with duct ligation. The distal stump was anastomosed with a Roux-en-Y
      jejunal loop. Neither pancreatic fistulas nor operative death occurred in any of
      the patients. In 3 patients with serous cystadenoma and in one with mucinous
      cystadenoma, the tumours measured 3.5 to 7 cm in size. These were located in the
      neck and body of the pancreas and could not be safely enucleated without
      compromising the pancreatic duct. All tumours were resected with clear margins.
      The mean operative time was 230 minutes and the median postoperative hospital
      stay 14 days (range: 10-23 days). The patients have been followed up for five
      years after surgery and all are disease-free. None of the patients became
      diabetic or presented exocrine insufficiency. Middle segment pancreatectomy may
      be an appropriate technique for selected benign or borderline pancreatic tumours
      in the neck and body of the pancreas. This procedure has an acceptable surgical
      risk when compared to that of major pancreatic resections and preserves
      pancreatic function and the spleen.

PMID- 11452817
TI  - [Laparoscopic appendectomy and laparotomy appendectomy: comparison of methods].
AB  - The study compares the real advantages of laparoscopic appendicectomy using only
      a transumbilical trocar, with laparotomic appendicectomy in the management of
      acute and/or chronic pain in the lower right abdominal quadrant. From May 1997 to
      April 2000, 88 patients were treated: 27 (group I) with the laparoscopic
      approach, and 61 (group II) with laparotomy. We compared operating times,
      incidence of complications, hospital stay and cosmetic result. We also reviewed
      the literature on this subject over the past ten years. Average operating time
      was 45 minutes in group I and 30 minutes in group II; complications consisted in
      2 cases of omphalitis in the laparoscopic group and 3 infections of the wound and
      2 cases of lipolysis of the abdominal wall in the laparotomic group. The average
      hospital stay was 3.2 days in the laparoscopic group against 4.7 days in the
      laparotomic group. Resumption of work and sport occurred after 10 to 20 days and
      15 to 45 days in groups I and II, respectively. The total cost was lower in the
      laparoscopic group. The laparoscopic approach appears to be an effective
      technique for the management of acute and chronic appendicitis, as it allows both
      treatment of the pathology and diagnosis and treatment of other unknown
      pathologies, with exploration of the abdominal cavity. In addition, it guarantees
      a good cosmetic result, a short hospital stay with a low incidence of
      complications and an advantageous cost/benefit ratio.

PMID- 11452818
TI  - [Use of mechanical staplers in the surgical treatment of rectal cancer in the
      elderly].
AB  - The aim of this study was to analyze the changes in surgical treatment of rectal
      cancer and in postsurgical complications as a result of the introduction of
      staplers in surgical practice, with particular reference to elderly patients (>
      or = 75 years). Since 1976, 320 patients have undergone rectal surgery in our
      department (207 colo-rectal or colo-anal anastomoses and 113 Miles operations
      have been performed). The patients were subdivided into two groups on the basis
      of age (> or = and < 75 years) and then further divided into subgroups operated
      on before and after 1983 (the year staplers were introduced). The morbidity rate
      (fistulas) was 16% in patients < 75 years old and 12% in elderly patients (P =
      n.s.); the mortality rate was 1% in patients < 75 years old and 12% in the more
      elderly group (P < 0.001). The utilization of staplers in surgical treatment of
      rectal cancer allows the surgeon to perform sphincter-sparing resections even in
      elderly patients without any changes in specific morbidity. Nevertheless, the
      complications are more severe in the elderly, with a higher mortality rate.

PMID- 11452819
TI  - Drainage in thyroid surgery: a prospective randomised clinical study.
AB  - Drainage in thyroid surgery is still an area of controversy. We analysed the
      results of a prospective randomised trial conducted in our institution in order
      to assess the utility of drainage after thyroid surgery. Sixty patients were
      entered into the study, thirty of whom were drained after surgery and thirty who
      received no drainage. The two groups were well matched with regard to most
      characteristics. There was no difference between the two groups in terms of early
      or late postoperative complications. We therefore conclude that, in our
      experience, drainage after uncomplicated thyroid surgery is of no benefit.

PMID- 11452820
TI  - [Intraoperative electron radiotherapy (IOERT) in the QUART sequence: a phase I
      study].
AB  - We evaluated the tolerance of a single dose of 800-1500 cGy, delivered with an
      electron beam from an IOERT-dedicated linear accelerator to the tumour bed in
      patients with breast cancer undergoing conservative treatment, instead of the
      traditional boost. We enrolled 27 patients (cT1-2, cN0). The first 6 received a
      dose of 800 cGy, 6 1000 cGy, 10 1200 cGy and 5 1500 cGy. External beam radiation
      therapy (EBRT) with a conventional schedule, 4000 cGy total dose, was performed
      after wound healing. The median gap between IOERT and EBRT was 8 weeks. Three
      patients with adverse prognostic factors undergoing chemotherapy, including
      doxorubicin or taxanes, received EBRT after completion of chemotherapy. One
      patient with a prosthesis implant had yielding of the surgical scar 8 months
      after IOERT (after 4 cycles of doxorubicin and 4 cycles of CMF complicated by
      frequent mastitis). Another patient with a large serum collection in the axilla
      manifested delayed scar formation. In the others no significant increase in
      healing time or surgery-related morbidity was observed. Another 4 patients
      developed mastitis. The cosmetic outcome was good in 26/27 patients. This
      treatment is well tolerated at all IOERT doses delivered. In the follow-up, to
      date, there have been no local relapses.

PMID- 11452821
TI  - [Role of radioisotopic lymphoscintigraphy in postphlebitic syndrome of the legs].
AB  - Post-phlebitis syndrome of the lower limbs is a set of symptoms that follow a
      state of phlebostasis and phlebolymphostasis with consequent oedema and tissue
      distress. We submitted 36 patients with post-phlebitis syndrome of the lower
      limbs to radioisotopic lymphoscintigraphy for the purposes of evaluating the
      vicariant function of the lymphatic system and the possible role of the lymphatic
      system in the genesis of dermo-epidermal abnormalities. The average age of the
      patients was 53.2 years (range: 43-69 years; M:F ratio: 0.50). The control group
      consisted of 6 healthy subjects. The average duration of the post-phlebitis
      syndrome in the patients studied was 8.5 years. We excluded from the study
      patients in whom a central cause was identified as being responsible for the
      pathogenisis of the oedema of the lower limbs. In addition, patients with
      obliterant arteriopathy were also excluded. Venous pathology was evaluated first
      clinically and then investigated by continuous-wave Doppler. As a first step,
      venous pressure was measured by Doppler phlebomanometry in clino- and
      orthostatism. All patients underwent radioisotopic lymphoscintigraphy with
      microcolloids using the Rijke technique. Radioactivity was monitored by means of
      a computerized gamma-camera. We classified the pathological findings of
      radioisotopic lymphoscintigraphy as follows: 1) delayed transit; 2) obstacles; 3)
      star-shaped superficial collateral lymphatic circulations; 4) lymphocoele or
      cutaneous lakes. A significant difference was detected (p < 0.05) between the
      pressure values in the post- phlebitis lower limbs and the pressure values in
      normal subjects. Combining the results of our measurements we recorded delayed
      transit in 5 patients (69.5%). This latter group included the cases with the
      severest forms of post-phlebitis syndrome. Therefore, better knowledge of the
      pathophysiology of the lymphatic system would appear to be useful in order to
      understand the origin and evolution of oedema of the lower limbs of patients with
      post-phlebitis syndrome. To this end, radioisotopic lymphoscintigraphy may be
      useful as a first-level examination in order to evaluate the capacity and
      efficiency of the lymphatic system.

PMID- 11452822
TI  - [Colonic perforation in patients undergoing colonoscopy].
AB  - Colonic perforations associated with colonoscopy are uncommon. We determined the
      incidence, clinical presentation, and medical and surgical treatments of
      iatrogenic colon perforations. We present the medical records of 8 patients with
      iatrogenic colorectal perforations seen over a period of 17 years. The median age
      68.3 years. Emergency laparotomy was performed in 7 patients. One case was
      treated with a medical approach. One postoperative death occurred. In the absence
      of significant contamination primary repair is the best treatment. Non-operative
      management is indicated in patients without peritoneal irritation.

PMID- 11452823
TI  - [Multidisciplinary approach to the patient with oropharyngeal dysphagia].
AB  - The Dysphagia Study Group of the Regional Hospital of Treviso uses a
      multidisciplinary approach to assess patients with oro-pharyngeal dysphagia. From
      1996 to 2000, 208 patients with functional dysphagia were studied by the Group.
      Dysphagia was due to neurological disease in more than 50% of patients, to
      surgery in 25% and to a functional disease in 17%. In patients less than 20 years
      old the aetiology was due to the aftermath of traumas; in patients aged from 20
      to 45 years the cause was a functional disease or achalasia, while in the
      majority of the older patients, aged over 45, had cerebral ischaemic lesions. The
      majority of patients (78%) were submitted to rehabilitation, 9.5% to medical
      treatment and 2.8% to surgery. Oro-pharyngeal dysphagia calls for a
      multidisciplinary approach in qualified centers with specialized facilities.

PMID- 11452824
TI  - [Surgical treatment in acute cholecystitis emergencies].
AB  - The aim of the study was to demonstrate the importance of early laparoscopic
      cholecystectomy for acute cholecystitis, without "conservative" treatment
      (intravenous fluids and antibiotics for 48-72 hours) to reduce inflammation.
      Early laparoscopic cholecystectomy reduces bile duct injury and the percentage of
      conversion to open cholecystectomy. Thirty-five patients with acute cholecystitis
      were submitted to early laparoscopic cholecystectomy, equally divided according
      to sex. All patients were submitted to US scans preoperatively and operated on by
      surgeons skilled in emergency laparoscopic operative techniques. Laparoscopic
      cholecystectomy was always performed with 4 trochars and the use of a 30 degrees
      laparoscope. Technical modifications during early laparoscopic cholecystectomy
      were drainage and decompression with subsequent de-tension and distention of the
      gallbladder. These manoeuvres entailed the use of Babcock, Endopatch (Ethicon)
      atraumatic forceps. In the presence of acute gallbladder inflammation we dissect
      the gall-blader well with a suction-irrigation tube. In patients suspected of
      having common bile duct stones, biliary duct injuries and/or anatomical changes
      due to inflammation, we perform intraoperative cholangiography. Five patients had
      conversion to open cholecystectomy (14.2%), in two cases (5.7%) for concomitant
      choledochal stones, in two cases (5.7%) for biliary peritonitis and in the fifth
      case (2.8%) for severe empyema of the gallbladder. Laparoscopic cholecystectomy
      was performed in 20 patients for acute cholecystitis (57.1%), in 9 patients for
      empyema (25.7%) and in 6 patients for gangrenous cholecystitis. Four cases
      presented postoperative complications owing to bile leakage from the liver bed,
      treated with antibiotic therapy. One patient presented jaundice on day 30 after
      laparoscopy owing to inadequate positioning of the clips on the cystic duct, near
      the common bile duct; ERCP was performed with application of a prosthesis, which
      was removed after two months. Our experience and results support the validity of
      early laparoscopic cholecystectomy in the treatment of acute cholecystitis,
      because it reduces the postoperative length of hospital stay and hospital costs.
      Early treatment is always helpful for inflamed and oedematous tissue which
      favours dissection, while dense, fibrotic adhesions hinder regular dissection
      with a greater risk of injury to the biliary duct and and a higher conversion
      rate to open cholecystectomy.

PMID- 11452825
TI  - Value of extended lymph node dissection in the treatment of gastric cancer.
AB  - Regional lymph node metastasis is a critical prognostic factor in gastric cancer,
      and extended lymph node dissection and routine microscopic examination of all
      resected nodes could potentially provide accurate information regarding lymph
      node status. On the other hand, the therapeutic value of extended lymph node
      dissection is controversial. While retrospective and prospective non-randomised
      comparative studies have shown that extended lymph node dissection significantly
      improves the survival rate, prospective randomised trials have failed to
      demonstrate the efficacy of extended dissection, although the number of patients
      in these studies was limited. The present review of the literature therefore
      considers the prognostic significance of regional lymph node metastases and the
      therapeutic efficacy of lymph node dissection performed for gastric cancer.

PMID- 11452826
TI  - [Neuromuscular and vascular hamartoma of the small intestine. Report of a
      clinical case and review of the literature].
AB  - We present the case of a 50-year old patient, operated on for three adjoining
      annular strictures in the jejunum with proximal dilatation. He presented with a
      one-year history of recurrent cramping in the upper abdomen and vomiting, with
      two episodes of intestinal obstruction. Microscopic examination of the stricture
      revealed, in the submucosa, disorganised fascicles of smooth muscle derived from
      the muscularis mucosae, bundles of non-myelinated nerve fibres with scattered
      abnormal ganglion cells and haemangiomatous vessels. The pathological findings
      observed were similar to those described as neuromuscular and vascular hamartoma,
      a rare stricturing condition of the small intestine. Many authors have questioned
      the hamartomatous nature of this disorder, since identical features may be seen
      in Crohn's disease, in ischaemic enteritis, in radiation enteritis and in non
      steroidal antiinflammatory drug-induced small intestinal strictures. On the basis
      of a review of the 5 previously described cases and of our own experience, we
      believe that neuro muscular and vascular hamartoma of the small bowel should be
      considered as a distinct entity if histological hallmarks of Crohn's disease are
      absent, in patients with no history of gastrointestinal disease, or of chronic
      ingestion of non-steroidal antiinflammatory drugs.

PMID- 11452827
TI  - Prostatic small cell carcinoma diagnosed by tru-cut needle biopsy: discussion of
      clinico-pathological findings.
AB  - The small cell carcinoma is a neuroendocrine tumour characterised by an
      aggressive clinical course and a high mortality rate. It occurs most commonly in
      the lung. Small cell carcinomas originating in the genitourinary system have been
      diagnosed with increasing frequency in recent years, because of the use of
      immunohistochemistry. Prostatic small cell carcinomas present the same biological
      behavior and similar histological, immunohistochemical and ultrastructural
      features to small cell carcinomas of the lungs. We describe the clinico
      pathological findings in a 65-year-old male patient with a diagnosis of prostatic
      small cell carcinoma, obtained by means of a tru-cut needle biopsy. We performed
      the immunohistochemical tests using neuron-specific enolase and chromogranin A
      antibodies, according to the literature. On the basis of our experience we stress
      the malignant features of small cell carcinoma and the difficulty in obtaining an
      early diagnosis and treatment because of the aggressive course of the lesion and
      the late symptomatology.

PMID- 11452828
TI  - Subcutaneous right leg metastasis from rectal adenocarcinoma without visceral
      involvement.
AB  - The occurrence of cutaneous metastasis from colorectal cancer is rare, with a
      reported frequency of less than 4 to 5 percent. Typically signifies widespread
      disease and a poor prognosis. Metastases from adenocarcinoma of the colon-rectum
      usually occur within two years of resection of the primary tumour, and the
      average survival of a patient with cutaneous metastasis has been reported as
      ranging from 3 to 18 months. The case reported here concerns a patient who
      developed a skin metastasis without evidence of visceral involvement after
      treatment of rectal carcinoma. It is advisable to implement cutaneous biopsy in
      patients with a history of carcinoma; this may establish the diagnosis of
      metastatic disease and change the methods of therapeutic intervention and
      prognosis.

PMID- 11452829
TI  - [Carcinoid of the appendix. Clinical report of 3 cases and diagnostic and
      therapeutic considerations].
AB  - The Authors report three cases of carcinoid of the appendix and discuss the
      difficult preoperative diagnosis and the different therapeutic options available.
      Over the period from January 1994 to December 1999, in the Surgery Unit of Penne
      Hospital, 424 appendicectomies were performed in 182 males and 242 females (age:
      12-86 years; mean age: 39.9 years). In three cases the histological response was
      positive for carcinoid of the appendix. No postoperative mortality or morbility
      were reported. The authors analyze the biological peculiarities and the
      prognostic factors associated with appendiceal carcinoid tumours, such as tumour
      size and the lymphatic or vascular infiltration of the mesoappendix (and the
      corresponding more aggressive surgical treatments) and recommend an appropriate
      postoperative follow-up since synchronous or metachronous bowel carcinomas are
      likely to occur. Pharmacological therapy has also made important progress, with
      the possibility of administering compounds capable of interfering with tumour
      development and neoplastic growth.

PMID- 11452830
TI  - [Intestinal occlusion caused by strangulated Morgagni-Larrey hernia: clinical
      case and review of the literature].
AB  - Morgagni-Larrey hernia is an infrequent, asymptomatic disease discovered by
      chance during routine radiological examination. It is usually congenital and non
      traumatic even in adults. Nevertheless, it can cause severe disturbances when
      complicated. We describe a case of strangulated Morgagni-Larrey hernia in a 73
      year-old lady admitted to the Emergency Room for abdominal pain, symptoms of
      intestinal occlusion and respiratory distress. Routine abdominal and chest x-rays
      revealed herniation of the stomach and transverse colon filling the entire right
      hemithorax with several air-fluid levels. A CT scan and a water-soluble contrast
      medium via a nasogastric tube confirmed the presence of the stomach and omentum
      in the right pleural cavity. Emergency laparotomy permitted reduction of the
      herniation and treatment of the diaphragmatic defect without resection.

PMID- 11452831
TI  - [Appendiceal mucocele associated with colonic neoplasm. Report of 2 cases and
      review of the literature].
AB  - Appendiceal mucocele is a rare entity frequently associated with colorectal
      cancer. We report two cases of mucocele associated with colorectal tumours. The
      first case (male, 64 yrs) is an appendiceal mucinous cystadenoma found
      incidentally during surgery for colon cancer. There is no evidence of disease
      after a 4-year follow-up. The second case (male, 66 yrs) is a mucocele associated
      with mucosal hyperplasia that was found during surgery for acute appendicitis
      with a periappendicular abscess. Endoscopic follow-up showed a rectal
      adenocarcinoma that was initially treated with local excision with T.E.M..
      Examination of the pathology specimen documented vascular invasion and the
      patient underwent curative colorectal resection. The preoperative radiological
      and endoscopic diagnostic procedures and the current therapeutic approaches
      described in the literature are reviewed. The relevance of the association
      between appendiceal mucocele and colorectal cancer is emphasized. Thorough
      investigation of the colorectal tract is recommended after diagnosing an
      appendiceal mucocele.

PMID- 11452832
TI  - [Inflammatory pseudotumor of the bladder: etiopathologic and clinical features].
AB  - The Authors present a case of inflammatory pseudotumour (IPT) of the urinary
      bladder occurring in a 57-year-old female patient, who was referred to our
      department with haematuria, stranguria and hypogastric pain. Ultrasonographic,
      radiological and endoscopic examinations showed a sessile, ulcerated, easily
      bleeding bladder formation; urinary cytology revealed no atypical transitional
      cells. Abdomino-pelvic computed tomography analysis showed thickening of the
      bladder walls and infiltration of the perivesical fat. Histopathologically, the
      formation was indicated as an inflammatory pseudotumour (IPT) of the bladder. The
      patient underwent TURB (transurethral resection of the bladder) and was
      discharged clinically healed on postoperative day 4. A one-year follow up
      revealed no evidence of recurrence. On the basis of their experience and a
      thorough review of the literature review, the Authors discuss the clinico
      pathological features of IPT of the bladder and the possible factors involved in
      the malignant transformation of IPT. In conclusion, the benign nature of the
      lesion is stressed.

PMID- 11452833
TI  - [Radioimmunoguided surgery (RIGS) in breast disease].

PMID- 11452834
TI  - Court examines privatization. Memorial Medical Center, Inc. v. Tatsch
      Construction.

PMID- 11452835
TI  - Whistleblower protection legislation examined by courts.

PMID- 11452836
TI  - Substance abuse counsellor's attitudes regarding lesbian, gay, bisexual, and
      transgendered clients.
AB  - PURPOSE: The attitudes of substance abuse counselors can have significant effects
      on their client's recovery. This study examined the attitudes and knowledge of
      substance abuse counselors regarding lesbian, gay, bisexual, and transgendered
      (LGBT) clients. METHODS: 242 substance abuse counselors in Iowa completed mail-in
      questionnaires. RESULTS: The counselors reported very little formal education
      regarding the needs of these clients, and nearly half had negative or ambivalent
      attitudes. Respondents had the greatest negativity regarding transgendered
      clients and reported knowing the least about this group. Counselors frequently
      lacked knowledge about the legal issues of these clients, the concepts of
      domestic partnership and internalized homophobia, and family issues.
      IMPLICATIONS: Substance abuse counselors require more education about LGBT
      clients.

PMID- 11452837
TI  - Maternal substance use during pregnancy and developmental outcome at age three.
AB  - PURPOSE: The data from the National Maternal and Infant Health Survey (NMIHS) and
      its 3-year follow-up offer a unique opportunity to study the effects of substance
      (alcohol, marijuana, and tobacco) use during gestation on development at age
      three in a nationally representative sample. Using this data, the relationship of
      development (language, gross motor, fine motor, and adaptive behavior) and
      specific behaviors (eating problems, length of play, activity level, difficulty
      of management, level of happiness, fearfulness, ability to get along with peers,
      tantrums, eating nonfood) and maternal drinking, marijuana use, and cigarette
      smoking was studied in a sample of live births who had been followed up at age
      three. METHODS: The data were analyzed using a cumulative logit model of ordinal
      responses. RESULTS: Higher activity level, greater difficulty of management,
      tantrums, eating problems, and eating nonfood were related to maternal drinking
      during pregnancy. Increased fearfulness, poorer motor skills, and shorter length
      of play were associated with maternal marijuana use during pregnancy. Less well
      developed language, higher activity level, greater difficulty of management,
      fearfulness, decreased ability to get along with peers, and increased tantrums
      were associated with maternal cigarette smoking during pregnancy. The
      preponderance of significant effects involved the behaviors studied rather than
      the developmental indices. IMPLICATIONS: It may be that the effects of substance
      use during pregnancy, especially more subtle ones, show up in behavior before
      they can be measured by developmental scales.

PMID- 11452838
TI  - Can the Treatment Services Review be used to estimate the costs of addiction and
      ancillary services?
AB  - PURPOSE: The economic costs of addiction treatment and ancillary services are of
      great interest to substance abuse treatment providers, researchers, and
      policymakers. This paper examines whether a widely used treatment evaluation
      instrument, the Treatment Services Review (TSR), can be used to estimate the
      costs of addiction and ancillary services. METHODS: The fifth edition of the TSR
      (TSR-5) is carefully reviewed and critiqued for cost estimation purposes. Unit
      cost estimates and sources are presented for most of the service delivery units
      on the TSR-5, and important missing service measures are identified. A cost
      analysis method is proposed that is based on data from the TSR. RESULTS: A
      variety of unit cost estimates are offered so that researchers and practitioners
      will understand how this financial information is compiled. However, the
      investigation determined that the TSR-5 is not currently structured for a
      comprehensive cost analysis of treatment services. The potential benefits and
      limitations of the TSR-5 as a cost analysis tool are identified and explained. In
      addition, recommended changes to the TSR-5 are suggested and described.
      IMPLICATIONS: Although not originally developed for economic evaluation purposes,
      with some modifications and enhancements, the TSR is an instrument that is
      capable of facilitating an economic cost analysis of addiction treatment and
      ancillary services. By combining service utilization information from a revised
      TSR (i.e., TSR-6) with reliable unit cost estimates for those services, future
      evaluation studies will be able to provide more standardized estimates of the
      costs of addiction and ancillary services for different types of treatment
      clients. When joined with outcome data, the TSR-6, along with the proposed cost
      module, can also be used to determine cost-effectiveness and benefit-cost ratios
      for subgroups of patients and treatment components.

PMID- 11452839
TI  - On substance abuse in Kuwait (1992-1997). Evidence from toxicological screening
      of patients.
AB  - PURPOSE: To assess preference for different psychoactive substances and time
      trends in Kuwait. METHODS: Analysis of urine and blood samples of specimens sent
      by attending physicians to the only public health reference laboratory for
      toxicological screening in the country. RESULTS: A total of 28,548 tests were
      performed on 3781 samples. Cannabinoids were positive in 40% of the tested
      samples, opiates in 24%, ethanol in 10%, and amphetamines in 5%. Elevated
      concentrations of methadone, cocaine, and phencyclidine did not exceed 0.1%.
      About 40% of samples was positive for benzodiazepines, but their therapeutic use
      obscures the informativeness of this finding. There was a significant increase in
      the proportion of positive results for ethanol, amphetamines, and
      benzodiazepines. IMPLICATIONS: It is high time to implement a modern and
      comprehensive preventive and control program. The tendency to blame the Iraqi
      invasion for drug addiction has hampered efforts to recognise and address the
      problem in its entirety.

PMID- 11452840
TI  - The one-year prospective prediction of substance abuse and dependence among high
      risk adolescents.
AB  - The present study examined 1-year prospective predictors of self-reported
      substance abuse and dependence among a sample of 702 youths at high risk for drug
      abuse from 21 southern California continuation high schools. Triadic influence
      theory was used as a theoretical guide. Predictors were selected as measures of
      triadic influence theory. Among 13 predictors, a drug use and intention index,
      and concern that one is or will become an addict or alcoholic, were consistently
      predictive of self-reported substance abuse or substance dependence 1 year later,
      controlling for baseline abuse or dependence status. In addition, baseline
      substance abuse, White ethnicity, and relatively poor prosocial coping predicted
      later substance dependence. Apparently, adolescents can predict their future use,
      and abuse or dependence status. Also, instruction in prosocial coping (e.g.,
      seeking social support) may help inhibit the transition from substance abuse to
      substance dependence.

PMID- 11452841
TI  - Demand characteristics of residential substance abuse treatment programs.
AB  - PURPOSE: This study examined the objective demand characteristics of treatment
      programs in which substance abuse patients, or psychiatric patients, were
      residing. It also examined associations of objective demand with substance abuse
      patients' perceived expectations for functioning during treatment and patients'
      in-program participation. METHODS: A total of 994 patients living in 79 programs
      took part. RESULTS: When patients had a substance abuse rather than a psychiatric
      problem, objective demand was higher: program policies had higher requirements
      for functioning and more resident control; programs offered fewer health
      treatment services; and the physical design provided fewer safety features and
      social-recreational aids. Compared to substance abuse patients in low-demand
      programs, patients in high-demand programs perceived the program to have higher
      expectations, in that the treatment climate exerted more press to develop
      relationships, set goals, and be organized. Patients in high-demand programs
      engaged more in self-initiated activities and participated more in treatment
      services and program-organized events. Substance abuse patients' activity and
      participation levels were determined jointly by the level of demand and by the
      expectations for patients' expressiveness and self-understanding of their
      personal problems. IMPLICATIONS: The findings illustrate the importance of
      considering objective indices of demand in conjunction with perceived
      expectations to improve patients' treatment outcomes.

PMID- 11452842
TI  - A meta-analysis comparing the effectiveness of buprenorphine and methadone.
AB  - Increases in the use of illicit opiates have refocused attention on these drugs.
      One outgrowth of this attention has been the increased consideration of
      pharmacotherapies to provide alternatives to methadone maintenance. Buprenorphine
      is one new tool used in the attenuation of illicit opiate use. Like methadone,
      buprenorphine produces cross-tolerance to other opiates. However, it may have
      advantages over methadone including a longer duration, limited withdrawal
      syndrome, and increased safety. Buprenorphine's ability to serve as a replacement
      drug for illicit opiate use is well documented, and efforts have recently been
      made to compare the drug with methadone. The purpose of this study was to provide
      a meta-analysis of all available research reporting a controlled comparison of
      buprenorphine and methadone. This analysis provided a rating of the comparative
      efficacy of each drug, thus giving clinicians an additional guide when selecting
      an appropriate course of treatment. Findings suggest a relative equality in the
      efficacy of buprenorphine and methadone, although patients receiving methadone
      were less likely to test positive for illicit opiate use. Past experience with
      methadone maintenance acted as a moderating variable, however, such that those
      receiving buprenorphine were more likely to stay drug-free in studies that
      included patients with prior methadone experience.

PMID- 11452843
TI  - Constituents of craving in a clinical alcohol sample.
AB  - PURPOSE: Craving describes a subjective state, and it remains unclear what people
      mean when they use the term. However, as with many other subjective states,
      craving should be able to be described by those who experience it. METHODS: To
      try to understand the descriptors and constituents of craving, 213 clients
      appearing for treatment for alcohol use disorders were asked to rate the
      frequency of the occurrence over the past 30 days of a number of events and
      states that have been historically regarded as part of craving. These clients
      were also asked to rate the frequency with which they had experienced craving and
      urges over the same period. Using discriminant function analysis (DFA), some
      states were elucidated that separated those who reported craving from those who
      did not. RESULTS AND IMPLICATIONS: Those who reported craving consistently
      reported the occurrence of more dysphoric states, more of certain physical
      feelings associated with thoughts of alcohol, more thoughts of alcohol, and
      desiring alcohol when confronted with environmental cues. Such descriptions may
      aid in establishing reliable criteria for understanding the constituents of
      craving.

PMID- 11452844
TI  - Deaths: preliminary data for 1999.
AB  - OBJECTIVES: This report presents preliminary data for 1999 on deaths in the
      United States. U.S. data on deaths are shown by age, sex, race, and Hispanic
      origin. Data on life expectancy, leading causes of death, and infant mortality
      are also presented. METHODS: Data in this report are based on a sample of deaths
      comprising more than 99 percent of the total deaths in the United States for
      1999. The records are weighted to independent control counts of infant deaths,
      and deaths 1 year and over received in State vital statistics offices for 1999.
      Unless indicated, comparisons are made with final data for 1998. Effective with
      this report, all age-adjusted death rates for 1999 and earlier years are
      standardized to the year 2000 population. Also, effective with mortality data for
      1999, causes of death are coded and classified according to the Tenth Revision of
      the International Classification of Diseases (ICD-10) replacing ICD-9 used in the
      United States for deaths occurring during 1979-98. RESULTS: In 1999 the age
      adjusted death rate for the United States increased slightly, compared with 1998.
      For causes of death, declines in age-adjusted rates occurred for homicide (6
      percent) and suicide (6 percent), while rates for Septicemia and hypertension
      increased 6.6 percent and 5.0 percent, respectively. Mortality also decreased for
      drug-induced deaths and deaths from injury by firearms. The infant mortality rate
      for the white population was down 3 percent, while the rate for the black
      population increased by 2 percent, but the increase was not statistically
      significant. Life expectancy remained the same at 76.7 years.

PMID- 11452845
TI  - Cerebellopontine angle meningiomas (cpam)--clinical characteristics and surgical
      results.
AB  - INTRODUCTION: About 10% of the tumourous lesions in the cerebellopontine angle
      are meningiomas according to the literature. Evidently, these tumours differ from
      the other lesions by their clinical presentation as well as by the surgical
      results, which will be presented in the following article. PATIENT MATERIAL: We
      report on 26 patients (22 females, 4 males: age distribution 45-81 years, mean 63
      years) operated on CPAM's in the last 8 years. Clinical history lasted from 2
      weeks to 9 years (mean 17 months). Cerebellar symptoms were the most frequent
      findings (n = 22), followed by cranial nerve (V, VII, and VIII) deficits (n = 12)
      and signs of increased intracranial pressure (n = 7). In 3 clinically
      asymptomatic cases the lesion was found incidentally, and there was 1 patient
      with a recurrent lesion. The radiological procedures included CT-scan in 17
      patients, MR-imaging in 18, MR-angiography in 2 cases and angiography in 2 cases.
      Hydrocephalus was demonstrated in 8 cases. Tumour size ranged from 2.8 to 7 cm
      (mean 4.2 cm). All patients underwent osteoclastic craniotomy with complete
      tumour removal. Temporary CSF-drainage was necessary in 8 cases, monitoring was
      done in 9 patients. RESULTS: Postoperative follow-up period ranged from 3 months
      to 5 years (mean 2.5 years). After 1 month, 14 patients were discharged home and
      12 were transferred into other hospitals in good condition. Improvement was
      achieved in 19 cases, 5 patients were equal to their preoperative situation, in
      one case a temporary deterioration with tetraparesis and in 1 case deterioration
      of hearing was found. After an average follow-up of 2.5 years, 22 patients were
      self-sufficient without or with minimal neurological deficits at home, 2 were
      moderately disabled and 2 died in the meantime due to other diseases. Among the
      operative complications, we observed 3 CSF-fistulas, 1 requiring surgical
      reexploration as well as 1 rebleeding and additionally 1 meningitis. Non-surgical
      complications were found in 5 patients. CONCLUSIONS: Cerebellar ataxia and
      impairment of hearing are the clinical leading symptoms of CPAM's. At diagnosis,
      these tumours are impressively large, but the operative results are very
      favourable with low morbidity and excellent prognosis.

PMID- 11452846
TI  - Cerebral vasospasm detection by TCD after supratentorial brain tumours surgery.
AB  - Serial transcranial Doppler ultrasonography (TCD) studies were carried out in 61
      patients, who had been operated due to supratentorial brain tumours. Among 61
      cases have been 26 gliomas, 19 meningiomas and 16 metastases. The Mean Flow
      Velocity (MFV) exceeding 120 cm/s in Middle Cerebral Artery (MCA) and 90 cm/s in
      Anterior Cerebral Artery (ACA) has been admitted as pathognomonic for vasospasm.
      The vasospasm has been stated in 14 cases (23%)--10 gliomas and 4 meningiomas out
      of 61 patients. The vasospasm has been more intense in ACA on the operated
      (lesion) side than in MCA and on the non operated (opposite) side.

PMID- 11452847
TI  - Study on ganglioside composition in brain tumours supra- and infratentorial.
AB  - The composition of gangliosides in primary tumors depends on their histological
      origin and differentiation grade (biological malignancy). The aim of the present
      study was the comparison of gangliosides in various types of brain tumours. The
      studies were performed on specimens from 20 high grade gliomas, 5 low grade
      gliomas, 8 meningiomas and 9 metastatic tumours. The isolated gangliosides were
      separated on silica 60 HPTLC plates and their mobilities were compared with
      glycolipids standards. The following observations were made: 1. high and low
      grade gliomas had similar ganglioside profiles comprising 7 different species; 2.
      the profiles of gangliosides isolated from metastatic neoplasms differ
      considerably from those of gliomas as well as menigiomas.

PMID- 11452848
TI  - Philosophy of neurosurgical posttraumatic rehabilitation at the beginning of the
      next millennium.

PMID- 11452849
TI  - Complications and neurosurgical interventions during early rehabilitation in head
      injured patients.
AB  - Guidelines for the treatment of traumatic brain injury (TBI) are subject of
      actual efforts in neurosurgery, anaesthesiology and traumatology as well as in
      the basic sciences. International collaborations such as European Brain Injury
      Consortium (EBIC), Pan-European-Advisory Board (PAB) and Euroacademy of
      Multidisciplinary Neurotraumatology (EMN) are working on pathophysiological
      understanding and evaluation of clinical outcomes to establish standards for a
      holistic concept from resuscitation to rehabilitation. We reviewed the courses of
      252 brain injured patients, treated over a four year period in our department
      including surgery, intensive care and early rehabilitation. Our special interest
      was focussed on complications during the early rehabilitation period and the
      neurological outcomes to define quantity and quality of monitoring as well as the
      need for invasive interventions at the interface between acute and rehabilitative
      medicine.

PMID- 11452850
TI  - Strategies in management of ruptured aneurysms--own experiences with various
      therapeutical procedures in severe SAH.
AB  - A retrospective analysis of 58 patients with spontaneous SAH was conducted. 33
      patients suffered on severe SAH, clinical grading IV and V (Hunt, Hess). 11 died
      without treatment due to decerebrate rigidity. 22 patients were treated, 16
      underwent a clipping procedure and 6 were selected for endovascular
      coilembolization. A total of 14 SAH were associated with intracerebral,
      intraventricular or subdural hemorrhages. In fact of these in 10 patients first
      an evacuation of the haematoma or a ventricular drainage was necessary, two times
      combined with a decompressive craniectomy. In 4 patients the removal of haematoma
      was combined with clipping of aneurysm in one operation. After occlusion of
      aneurysm decompressive craniectomy was required in 3 patients, an evacuation of
      an intracerebral bleeding in 1 patient. 6 patients needed a permanent shunting
      system. The outcome according the Glasgow Outcome Score was: 4 died (GOS1), 12
      were severely disabled (GOS3) and 6 were moderately disabled (GOS4).

PMID- 11452851
TI  - Combined treatment of cerebral aneurysms with utilization of clipping and coiling
      techniques.
AB  - Cerebral aneurysm clipping is a widely used and accepted treatment option.
      However, in some patients in severe condition (IV and V WFNS grade), with
      aneurysms of basilar and vertebral part of the arterial circulation and with high
      general surgical risk, direct aneurysm surgery can be a real technical and
      clinical problem. Therefore, low risk of coiling procedures gain more and more
      support. Out of 218 patients with diagnosed aneurysms, 60 were selected for
      coiling treatment, and 15 patients with multiple aneurysms were treated with both
      procedures. Special attention has to be addressed to the selection of patients
      for coiling procedures, especially in the cases when aneurysmal neck is directed
      accordingly to the main blood stream. The follow-up of the treatment effects is
      necessary. In the cases with growing aneurysms clipping is recommended. In the
      cases with stable size of the aneurysmal sack and visible coils compression, the
      coiling procedure is repeated. The coiling procedures can offer a valuable
      treatment option for selected patients. However, the maintenance of permanent
      occlusion of the aneurysm sack after coiling gives rise to some controversy.

PMID- 11452852
TI  - Approaches to posterior circulation aneurysms and results of the operations.
AB  - Surgical approaches and operative results in 32 operations of aneurysms of the
      vertebrobasilar system are presented. The orbitozygomatic and temporopolar
      approach was used for aneurysms of the bifurcation of the basilar artery lying
      high in the interpeduncular fossa. In aneurysm which neck was located less than
      10 mm above or less than 5 mm below the anterior and posterior clinoid processes
      the pterional transylvian subtemporal and pterional anterior temporal approaches
      were performed. A large aneurysm with the neck lying 5 mm below the line
      connecting the anterior and posterior clinoid processes was operated on via
      pterional transcavernous approach. The used approaches made it possible to clip
      the aneurysms. Good and very good results were obtained in 82 per cent of cases.
      The perioperative mortality was 9 per cent.

PMID- 11452853
TI  - Giant brain aneurysm--difficulties in diagnosis and treatment. Case report.
AB  - Aneurysms of diameter above 25 mm, determined as giant aneurysms, are thought to
      be surgically difficult. The most common symptom of the presence of aneurysm is
      subarachnoidal hemorrhage. Giant aneurysm may cause focal neurological symptoms,
      very rarely may show symptoms of intracranial hypertension. In the presented case
      a 47-year old woman after the first epilepsy attack the dominated symptoms were
      those of intracranial hypertension. CT suggested brain tumour of 70 mm diameter.
      Brain angiography revealed giant aneurysm of the left middle cerebral artery.
      After having considered differed method of therapeutic management, microsurgical
      operative technique was applied in general anesthesia with brain protection.

PMID- 11452854
TI  - Influence of intraoperative using of recombinant tissue plasminogen activator on
      the development of cerebral angiospasm after subarachnoid haemorrhage in patients
      with ruptured intracranial aneurysms.
AB  - For a few years conducted experimental studies and clinical trials set one's
      hopes on the role of the fibrynolytic treatment using recombinant tissue
      plasminogen activator (rt-PA) in preventing cerebral vasospasm. In our study the
      target population was 45 patients with ruptured saccular aneurysms causing severe
      SAH. In the group of 24 patients treatment consisted of a single intraoperative
      injection of 10 mg of rt-PA into the opened basal subarachnoid cisterns following
      aneurysm clipping. The patients underwent surgery with aneurysm clipping within
      72 hours from subarachnoid haemorrhage in all patients. Control group of 21
      patients underwent early operation after SAH and rt-PA was not given. All
      patients had significant basal cistern blood accumulation seen on CT scans
      preoperatively according to Fisher's grade III. Patients in our study were
      classified in clinical grade I and II according to classification of Hunt/Hess.
      Transcranial Doppler Daily examinations in postoperative course were performed in
      all patients. The postoperative results were evaluated according to Glasgow
      Outcome Scale. Postoperatively patients were evaluated by daily transcranial
      Doppler and serial CT scans. TCD demonstrated reduction in the development of
      vasospasm to a greater degree in the rt-PA treated group. Serial CT examinations
      demonstrated radical blood clot removal in all rt-PA treated patients. The
      postoperative results according to the Glasgow Outcome Scale in the rt-PA treated
      group were as follow: 22 patients were grades I and II, 2 patients were grade
      III. In the control group 13 patients were grades I and II, 6 patients were grade
      III, and 2 patients died. In the rt-PA treated group only one patient presented
      delayed ischemic deficit.

PMID- 11452855
TI  - Our own experience with CT angiography in early diagnosis of cerebral vascular
      malformations.
AB  - Computed tomography (CT) and intraarterial cerebral angiography are essential
      methods in early diagnosis of cerebral vascular malformations. In recent years
      however non-invasive or minimally invasive methods like MR angiography and CT
      angiography (CTA), which could potentially replace angiography, have been
      developed. The aim of presented study is to demonstrate our own experience in
      application of CTA in early diagnosis of cerebral vascular malformations. The
      material consists of 86 CTA examinations performed shortly after non-traumatic
      intracranial haemorrhage. Angiographic correlation has been available in 23
      patients and surgical one--in 31 cases. CTA studies began with serio-CT to select
      the optimal time between contrast injection and CT scanning. After that 100-120
      ml of non-ionic contrast medium was injected intravenously (5 ml per sec.) and
      spiral CT acqusition was performed with the delay calculated on the basis of the
      serio-CT. The obtained images were postprocessed on the workstation using always
      MIP and in many cases also SSD and VRT reconstructions. Vascular malformations
      have been diagnosed in 44 of 86 CTA studies including 38 patients with aneurysms
      (total number 51) and 6 patients with AVMs. In 17 cases the diameter of the
      aneurysm did not exceed 5 mm. In all surgical cases the CTA diagnosis of the
      aneurysm has been confirmed. There was however one false-negative case. On the
      other hand in 7 patients CTA revealed the small aneurysm, despite unclear
      angiographic appearance. In 2 of 6 patients with CTA suspicion of AVM this
      diagnosis has been excluded either by angiography or surgery. Comparison of CTA
      and angiography in 22 aneurysms showed in 17 cases superiority of CTA in
      evaluation of aneurysmal neck and the relationship between aneurysm and adjacent
      vessels (especially with VRT and SSD reconstructions). In patients with AVMs
      however the evaluation of supplying and draining vessels was better with
      angiography. On the base of our material we can conclude that CTA is very
      efficient in detecting and evaluating the aneurysms. We believe that CTA can
      replace angiography if it reveals aneurysm in a site corresponding with location
      of haemorrhage on CT. In patients with suspicion of AVM value of CTA is doubtful
      and angiography remains the method of choice.

PMID- 11452856
TI  - Factors leading to hydrocephalus after aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: The predisposing factors for the development of posthemorrhagic
      hydrocephalus, requiring shunt implantation, after subarachnoid hemorrhage (SAH)
      are still not exactly known. Therefore we analyzed the patients with SAH, who
      were treated in our department with respect to the development of chronical
      cerebro-spinal fluid (CSF) imbalance, trying to define predictive parameters for
      this entity. METHODS: All patients presenting with SAH were analyzed
      retrospectively between September 1992 and July 1998. Special consideration was
      given to the initial CT scan (cistern index, Fisher grade, bicaudate index) and
      the requirement for an external ventricular drainage. Other possible predictive
      factors as age, Hunt & Hess grade, electrolyte disturbances and operative
      techniques were also evaluated. RESULTS: During the investigation period, 283
      patients presenting with aneurysmal SAH underwent surgery. Fifty-two patients
      (18.4%) required a shunting procedure due to chronic posthemorrhagic
      hydrocephalus. The mean time interval between the initial bleeding and shunting
      was 28 days. All of these patients required a significantly longer external CSF
      drainage (p < 0.001) with a much higher amount of daily drained CSF (p < 0.001).
      The evaluation of the initial CT scan revealed no correlation between the amount
      of blood and later shunt dependency. However, there was a significant correlation
      with the bicaudate index (p < 0.01). CONCLUSION: Chronic hydrocephalus after
      aneurysmal SAH is an important complication. The recovery-time of shunt dependent
      patients is definitely prolonged compared to non-shunted patients. Predictive
      factors of shunt dependency seem to be length and amount of the external CSF
      drainage, as well as a high bicaudate index.

PMID- 11452857
TI  - Quality of life after SAH and clipping of cerebral aneurysm.

PMID- 11452858
TI  - Anterior cervical spine fusion using RABEA-Titan-Cages avoiding iliac crest
      spongiosa: first experiences and results.
AB  - INTRODUCTION: In cervical discectomy using the ventral approach both, the
      necessity of replacement of the removed disc space itself as well as the material
      of the graft, if used, is still a matter of discussion. New approaches are titan
      cages, usually filled with autologeous spongiosa. We present in the following
      study our first experiences using the hollow RABEA-Titan-Cages without filling
      with spongiosa to avoid the iliac crest complications. MATERIAL AND METHODS: 63
      patients (33 male, 30 female, age 25-79 years, mean 52 years) were operated on a
      degenerative cervical disc herniation by ventral discectomy and replacement of
      the disc by the cage for fusion. The mean follow-up was 8 months. The
      preoperative symptoms were radiculopathies (n = 43) and myelopathies (n = 20).
      The diagnosis was confirmed by CT, MRI, myelography/CT and functional plain x-ray
      examination excluding instability. Level of the disc herniation: C3/4 n = 3, C4/5
      n = 4, C5/6 n = 21, C6/7 n = 23, C7/Th1 n = 5, and 7 cases with 2 levels. In 30
      cases we found hard discs, in 13 cases soft discs and in 20 patients combined
      lesions. All patients were intra- and postoperatively controlled by x-ray
      examination. RESULTS: Free of complaints were 17 patients, a marked improvement
      was found in 33 cases, a minor improvement in 10 cases, from those 4 patients
      additionally suffered from depression or alcoholism and 1 patient had a trauma in
      the history. 3 patients showed no change. Minor neck pain was reported in 5
      cases. The mean postoperative hospitalisation was 8 days. Surgery related
      complications: temporary radicular palsies n = 5, hoarseness/problems with
      swallowing n = 5. In 2 cases (3%) with osteoporosis surgical revision of the cage
      was necessary (one case with ventral dislocation and one case with recurrent
      nerve root compression). In all other cases the x-ray control proved the correct
      placement of the cages intra- and postoperatively on discharge. CONCLUSION: For
      the anterior cervical fusion, the hollow RABEA-Titan-Cages present good clinical
      results and help to avoid complications from the iliac crest donor site. For long
      term results, a longer follow-up and a increased number of patients is required.

PMID- 11452859
TI  - Tramadol for postoperative analgesia in intracranial surgery. Its effect on ICP
      and CPP.
AB  - An ideal analgesic for patients after craniotomy should neither cause respiratory
      depression, nor affect intracranial pressure (ICP) and cerebral perfusion
      pressure (CPP). The aim of the study was to evaluate the effect of Tramadol (T)
      on ICP and CPP, as well as to determine its analgetic efficacy in patients (pts)
      after craniotomy. Thirty five pts aged 16 divided by 78 years (mean 46) entered
      the study. Twelve had GCS (Glasgow Coma Scale) scores < or = 8 and 23 pts had
      scores > or = 12. Fourteen pts were mechanically ventilated and 21 pts were
      breathing spontaneously (BS). Tramadol was injected i.v. at a dose of 0.75 mg/kg
      over 3 minutes in 11 pts (Group 1), 1.0 mg/kg over 5 minutes in 13 pts (Group 2)
      and 1.0 mg/kg over 10 minutes in 11 pts (Group 3) PaCO2 was measured before T in
      all pts and at 8 minute after injection in 21 BS pts. Heart rate (HR), mean
      arterial blood pressure (MBP), ICP, CPP and respiratory frequency (f) were
      registered before and in the 1st, 3rd, 8th, and 15th minute after T. Analgetic
      effect was evaluated in 22 conscious pts by comparing the pain intensity before
      and 30 minutes after T using a five-point verbal response scale. Mean control ICP
      was 17 mmHg. ICP over 15 mmHg was diagnosed in 15 pts (mean ICP equal 26 mmHg).
      Mean CPP for all 35 pts was 85 mmHg. There were no statistically significant
      changes in HR, MBP, ICP, and CPP after T in any particular group, nor were there
      changes in ICP in subgroups with normal and elevated ICP. No significant changes
      in PaCO2 and f were found in BS pts. Satisfactory analgesia was obtained in 50%
      of pts of Group 1, and in 88% of pts of Groups 2 and 3. We conclude that tramadol
      in doses of 0.75 mg/kg and 1.0 mg/kg i.v. does not affect ICP and CPP in adult
      postcraniotomy patients and seems to be a safe and effective analgesic at a dose
      of 1.0 mg/kg for postcraniotomy pain control.

PMID- 11452860
TI  - The concept of cerebral circulatory-pressure index (CCPI).
AB  - The theoretical relations between blood pressure (MABP), intracranial pressure
      (ICP) and cerebral perfusion pressure (CPP) as well as the new Cerebral
      Circulation-Pressure Index (CCPI) are presented in the paper. The special
      nomogram collecting all of these parameters was constructed. CPPI was defined as
      a quotient of CPP and ICP: [formula: see text] CCPI reflects the relationship
      between the systemic MABP and ICP and for ensuring the normal conditions of
      intracranial circulation the MABP must be at least 4 divided by 5 times higher
      than ICP. The low values of CCPI, if they are not immediately corrected, results
      on severe brain disability or even death. We didn't find till now what should be
      the upper limit of CCPI, which overcrossing may be danger for the patient,
      especially with impaired autoregulation. Based on analysis of patients operated
      due to intracranial disorders as brain tumours, spontaneous and traumatic
      haematomas as well as ruptured aneurysms we find that the values of CCPI over 3
      have a good prognosis, between 3 and 2 is a field for intensive treatment
      consisting on decreasing ICP or increasing the systemic blood pressure or both.
      If CCPI is below 1.5 the prognosis is pessimistic and all the patients died. CCPI
      together with the nomogram are useful in current evaluation of the state of
      patients and of the efficacy of treatment and prediction of the treatment
      results.

PMID- 11452861
TI  - Mechanical properties of the human brachial plexus.
AB  - This study shows measurements of force and elongation during experimental
      traction of human brachial plexus. Experiments were realised on fresh cadaveric
      specimens, mechanism of traction injury of brachial plexus was simulated.
      Predominant lesion provoked by direct lateral traction of isolated brachial
      plexus was avulsion of the roots. Epineural mechanical failure as first lesion
      occurred at anterior margin of avulsed roots in the proximity of intervertebral
      foramen. The force leading to rupture of brachial plexus ranged between 217.7N
      546.3N, stress value between 1.3 N/mm2-3.5 N/mm2. Elongation until rupture was
      19.6%-58.8% of initial length.

PMID- 11452862
TI  - Conception of the cervico-brachial protector for motorcycle drivers.
AB  - The increasing popularity of motorcycles increases the role of motorcycle
      accidents as a main cause of brachial plexus injuries. In view of the high social
      cost of treatment of the victims it seemed desirable to devise some kind of
      protective clothing for motorcyclists. The protective clothing devised by teams
      from Department of Neurosurgery, TRICOTEXTIL--and Aeronautics and Applied
      Mechanics Institute, consists of the following parts: cervical collar--acting
      against force causing lateral bending and extension of cervical spine, shock
      absorptive shoulder pads--acting against the impact energy partially absorbing it
      and partially transmitting to the dorsal stiff bar, dorsal stiff bar and
      sacroiliac belt--partially immobilizes the thoracic and lumbar spine, acts
      against its compression, transmits the impact energy to the iliac crests and
      hips. The expected biomechanical effects of the cervico-brachial protector are as
      follows: In brachial region it should diminish the impact energy by its partial
      absorption and partial transmission along dorsal stiff bar to sacroiliac belt. It
      should act against excessive cervical spine motion--mainly against lateral
      bending and extension. It should act against excessive depression of the
      shoulder. The protective system built in the jacket should co-operate with the
      helmet of motorcycle driver. It should be comfortable for the driver and conform
      to security standards. Prototype of the protector underwent kinetic sledge tests
      in Industrial Motorization Institute (PIMOT), Warsaw, with the use of Hybrid
      Dummy II.

PMID- 11452863
TI  - Home mechanical ventilation--a logistic and human medical challenge.

PMID- 11452864
TI  - Survey of children supported by long-term mechanical ventilation in Switzerland.
AB  - OBJECTIVE: The aim of the present study was to identify the number of children,
      from birth to 16 years of age, on long-term mechanical ventilation in
      Switzerland, and to establish their current location, underlying diagnoses and
      ventilatory needs. METHODS: Postal questionnaires were sent to all chest
      physicians (pulmonologists), intensive care specialists, neurologists, national
      health care organisations, rehabilitation services and ventilator suppliers known
      or thought to be involved in paediatric long-term ventilation in Switzerland.
      RESULTS: Detailed information was obtained on 32 children from 7 centers.
      Underlying disorders included congenital central hypoventilation syndrome (CCHS,
      41%), neuromuscular disorders (41%), spinal cord injury (6%), craniofacial
      anomalies (6%) and others (6%). 10 children received positive pressure
      ventilation by tracheostomy and 19 children by nasal mask. Two children were
      ventilated by phrenic nerve pacing and one child with the help of a pneumatic
      belt. Children with CCHS were almost equally divided into nasal mask and
      tracheostomy users. Ventilation for 16-24 hours a day was necessary in 5
      children, exclusively during sleep in 24 children and only episodically in 3
      children. All but 2 children were cared for at home. The majority of families
      received home care support. The most common reasons for readmission into hospital
      were regular follow-up examinations and respiratory tract infections. The
      children were mainly admitted to paediatric intensive care units. CONCLUSIONS:
      There are few ventilator-supported children in Switzerland and most of them are
      cared for at home. Nevertheless, there is a need to establish a system for
      continuing data collection in this particular patient population to assess
      outcome and quality of home care support and to follow incidence trends.

PMID- 11452865
TI  - Survivors with bad outcome after hypoxic-ischaemic encephalopathy: full-term
      neonates compare unfavourably with children.
AB  - Hypoxic-ischaemic encephalopathy (HIE) is of major importance in neonatal and
      paediatric intensive care with regard to mortality and long-term morbidity. Our
      aim was to analyse our data in full-term neonates and children with special
      regard to withdrawal of life support and bad outcome. PATIENTS: All patients with
      HIE admitted to our unit from 1992-96 were analysed. Criteria for HIE were
      presence of a hypoxic insult followed by coma or altered consciousness with or
      without convulsions. Severity of HIE was assessed in neonates using Sarnat
      stages, and in children the duration of coma. In the majority of cases staging
      was completed with electrophysiological studies. Outcome was described using the
      Glasgow Outcome Scale. Bad outcome was defined as death, permanent vegetative
      state or severe disability, good outcome as moderate disability or good recovery.
      RESULTS: In the neonatal group (n = 38) outcome was significantly associated with
      Sarnat stages, presence of convulsions, severely abnormal EEG, cardiovascular
      failure, and multiple organ dysfunction (MOD). A bad outcome was observed in 27
      cases with 14 deaths and 13 survivors. Supportive treatment was withdrawn in 14
      cases with 9 subsequent deaths. In the older age group (n = 45) outcome was
      related to persistent coma of 24-48 h, severely abnormal EEG, cardiovascular
      failure, liver dysfunction and MOD. A bad outcome was found in 36 cases with 33
      deaths and 3 survivors. Supportive treatment was withdrawn in 15 instances, all
      followed by death. CONCLUSIONS: Overall, neonates and older patients did not
      differ with regard to good or bad outcome. However, in the neonatal group there
      were significantly more survivors with bad outcome, either overall or after
      withdrawal of support. Possible explanations for this difference include
      variability of hypoxic insult, maturational and metabolic differences, and the
      more compliant neonatal skull, which prevents brainstem herniation.

PMID- 11452866
TI  - Distinct endobronchial expression of matrix-metalloproteinases (MMP) and their
      endogenous inhibitors in lung cancer.
AB  - BACKGROUND: Degradation of extracellular matrix (ECM) and basement membranes is
      required for tumour cell invasion and metastasis. The ECM is degraded by matrix
      metalloproteinases (MMP) which are counteracted by tissue inhibitors of
      metalloproteinases (TIMP). In aggressive tumours the balance of proteolysis and
      antiproteolysis is disrupted, resulting in fast tumour progression and
      invasiveness. We examined MMP and TIMP expression patterns in bronchial washings
      of 58 consecutive lung tumour patients and 10 controls. Pathohistological
      investigations revealed squamous cell carcinoma (n = 23), adenocarcinoma (n =
      18), small cell lung carcinoma (n = 9), and pulmonary metastases of
      extrapulmonary tumours (n = 8). MMP/TIMP expression was correlated to histology,
      location, or staging of tumours. METHODS: Expression and activity of MMP was
      identified by zymography and Western blotting. Expression of TIMP-1 and TIMP-2
      was analysed by Western blotting and enzyme-linked immunosorbent assays. RESULTS:
      We identified MMP-1, MMP-2 and MMP-9, but not MMP-3 or MMP-8 in bronchial
      washings. All MMPs were expressed in the tumour-affected and the tumour-free
      parts of the lung. While MMP-1 and MMP-9 were present in all samples, the
      inactive precursor of MMP-2 was specifically expressed in adenocarcinoma or lung
      metastases of extrapulmonary tumours. No MMP-2 was found in controls. While TIMP
      1 was expressed in all samples, TIMP-2 was not detectable. CONCLUSION: The tumour
      type-specific expression of the MMP-2 precursor in adenocarcinoma and lung
      metastases suggests that MMP-2 in the absence of TIMP-2 correlates with
      aggressive tumour progression and may serve as an indicator for poor prognosis.

PMID- 11452867
TI  - Prevalence of colonisation and resistance patterns of vancomycin-resistant
      enterococci in healthy, non-hospitalised persons in Switzerland.
AB  - In order to obtain data about the prevalence and the resistance profiles of
      vancomycin-resistant enterococci (VRE) in the community, we investigated fecal
      samples of employees (n = 1026) from food processing companies of different Swiss
      cantons. The susceptibility of the isolated VRE-strains against penicillin,
      ampicillin, tetracyclin, ciprofloxacin, chloramphenicol, streptomycin and
      gentamicin as well as the minimal inhibitory concentrations (MIC) for vancomycin
      and teicoplanin were determined by agar diffusion and microbroth dilution,
      respectively. The type of vancomycin-resistance (vanA, vanB, vanC1, -C2 or -C3)
      was confirmed by polymerase chain reaction (PCR). A ratio of 50 samples out of
      1026 (4.9%) was found VRE-positive, all of the isolated strains carried the vanA
      resistance gene. Compared to recent publications from other European countries,
      these results represent a rather high prevalence of VRE-carriers in the
      community.

PMID- 11452868
TI  - Studies of phosphorescent probes for proteins.
AB  - 1. Certain capabilities and limitations of using bound phosphorescent
      chromophores to study protein structure were investigated. Carbonic anhydrase
      inhibitors with three different arrangements of singlet and triplet energy levels
      relative to those of tryptophan were used to determine their ability to transfer
      triplet energy. 2. Ligands representing each of the three spectroscopic energy
      level arrangements were found to exhibit triplet-triplet energy transfer with a
      tryptophan residue at the active site of carbonic anhydrase. This greatly
      increases the number of ligands which may be useful as phosphorescent probes. 3.
      The efficiency of energy transfer occurs to varying degrees depending upon the
      inhibitor. This is a potential source of data for determining the position of the
      ligand in the binding site.

PMID- 11452869
TI  - Circular dichroism studies on coat proteins of some strains and mutants of
      tobacco mosaic virus.
AB  - 1. Tobacco mosaic virus (TMV) protein has in near ultraviolet a complex but well
      resolved circular dichroism (CD) spectrum at room temperature. There are seven
      positive bands at 248, 252, 257, 265, 274, 281 and 291 nm, and a negative one at
      296 nm. The CD spectrum is pH-dependent. The shape of the pH-dependence curves
      and the comparison with CD spectra of model compounds suggest that the bands at
      248, 252 and 257 nm are mainly caused by phenylalanyl, those at 265, 274 and 281
      nm by tyrosyl, and those at 291 and 296 nm by tryptophanyl side chains. 2. Only
      insignificant changes of the tertiary structure seem to occur between pH 6.5 and
      8.5. Changes in ellipticity of TMV protein during the pH-induced polymerization
      reaction suggest that: (1) tyrosyl residues are involved in the binding of
      subunits, (2) phenylalanyl residues seem to be transferred to a less rigid
      environment, and (3) tryptophanyl residues are not essential for the reaction. 3.
      The proteins of several TMV strains and mutants studied have similar far
      ultraviolet CD spectra and apparently do not differ significantly in their
      structure. Their near ultraviolet CD spectra are, however, different.
      Replacements involving aliphatic amino acids do not change considerably the near
      ultraviolet CD spectra. On the other hand, replacements involving aromatic amino
      acids have a great effect on the spectra rendering possible identification of CD
      bands and recognition of the aromatic amino acid residues responsible for optical
      activity.

PMID- 11452870
TI  - A magnetic study of acidic ferric hemoglobin.
AB  - In this article, we have extensively studied and discussed the magnetic
      properties of acidic ferric hemoglobin and its isolated chains. The magnetic
      susceptibility, EPR and optical spectra of those samples were measured in the
      temperature region below 77 degrees K. By the magnetic susceptibility
      measurements, it could be made clear that at an acidic pH value, both ferric
      hemoglobin and its isolated chains were constituted of a mixture of two spin
      states (high-spin state S = 5/2 and low-spin state S = 1/2) and the ratio of this
      mixture varied in each protein sample, but was independent of the temperature
      change below 77 degrees K. The co-existence of these two components could be
      ascertained by the observation of EPR spectra at liquid hydrogen temperature.
      Acidic ferric hemoglobin and its isolated chains exhibited the two components of
      EPR spectra which corresponded to their magnetic susceptibility, and it was found
      that the relaxation time of the low-spin state was longer than that of the high
      spin state. The low-spin component of EPR spectra was almost undetectable at
      liquid nitrogen temperature. The three principal g values of this low-spin were
      gz = 2.80, gy = 2.20, and gx = 1.70. At alkaline pH values these low-spin
      components and the high-spin component of EPR spectra were displaced by the
      different low-spin spectra which corresponded to the ferric hemoglobin-hydroxide
      complex. It seems that the magnetic properties of the high-spin component are the
      same as the acidic ferric myoglobin, and the fine structure of the iron ion also
      seems to be same. Optical spectroscopy also gave similar magnetic properties
      which corresponded to the magnetic measurements.

PMID- 11452871
TI  - Molecular-orbital study of hydroxylation of collagenous proline and lysine.
AB  - EHT and CNDO/2 types of calculations permit the interpretation of the course of
      hydroxylation of collagenous proline and lysine. Calculations were performed for
      the models of proline (I), zwitterion of proline (II), proline-containing peptide
      (III), and lysine (IV). The theoretical results are consistent with an
      electrophilic mechanism.

PMID- 11452872
TI  - A study of collagen and gelatin solutions by optical self beat spectroscopy.
AB  - A study of the conformation of collagen and gelatin in aqueous solution by
      Optical Self Beat Spectroscopy is reported. The translational diffusion
      coefficient of monomeric tropocollagen was experimentally measured from the half
      width of the Rayleigh scattered radiation and the value obtained is shown to be
      in good agreement with that calculated from hydrodynamical theory for the
      tropocollagen rod. The Self Beat Spectrometer was also used to investigate the
      factors affecting the aggregation and flexing of molecules in dilute gelatin
      solutions and the gel-sol transition in more concentrated gelatin solutions.

PMID- 11452873
TI  - The amino acid sequence of rape (Brassica Napus L) cytochrome c.
AB  - The amino acid sequence of rape (Brassica Napus L) cytochrome c was determined
      using 1 mumole of protein. Analysis of chymotryptic and tryptic peptides by the
      dansyl-Edman method showed that the molecule consisted of 111 residues and was
      homologous with other mitochondrial plant cytochromes c. The amino acid sequence
      was found to be identical with that previously reported for the cytochrome c from
      cauliflower (Brassica oleracea L).

PMID- 11452874
TI  - Studies on the status of free amino and carboxyl groups in cobrotoxin.
AB  - The status of free amino groups in cobrotoxin was studied by stepwise
      modification with trinitrobenzene sulfonate. Lys-27 was selectively modified
      without altering the activity of cobrotoxin. However, complete loss of activity
      was observed when Lys-27 and Lys-47 were trinitrophenylated, suggesting that the
      epsilon-amino group of Lys-47 is essential for the activity of cobrotoxin. The
      alpha-amino group of N-terminal leucine had no correlation with activity,
      demonstrated by the guanidination of the lysine residues with O-methylisourea
      followed by trinitrophenylation of the alpha-amino group. The carboxyl groups in
      cobrotoxin were modified with glycine methyl ester after activation with water
      soluble carbodiimide. Six out of seven free carboxyls reacted in the absence of
      guanidine.HCl without altering the biological activity. When the remaining
      carboxyl was modified in the presence of 5 M guanidine.HCl, the resulting toxin
      was devoid of activity. This "buried" carboxyl is essential for activity and was
      identified as the gamma-carboxyl group of Glu-21.

PMID- 11452875
TI  - Guanidination and nitroguanidination of staphylococcal enterotoxin B.
AB  - Guanidination of the free amino groups of staphylococcal enterotoxin B with 3,5
      dimethyl-1-guanylpyrazole converted 31-32 of 33 epsilon-amino groups and 30% of
      the N-terminal residue. This product, although markedly reduced in solubility,
      suffered no gross change in conformation and retained full biological activity. A
      derivative prepared by reaction with O-methylisourea with only one lysyl residue
      unaltered lost most of its emetic activity. Nitroguanidination with 3,5-dimethyl
      1-nitroguanylpyrazole converted up to 28 of the epsilon-amino groups and
      essentially all of the N-terminus. This material was greatly reduced in ability
      to produce emesis and like the O-methylisourea prepared guanidinated enterotoxin,
      gave only a line of partial identity in double diffusion. The loss of activity is
      attributed to unfolding and it is concluded that the free amino groups of
      enterotoxin B do not critically participate in either its antigenic determinants
      or its active center for emesis.

PMID- 11452876
TI  - The effect of adjacent residues on the reactivity of tyrosyl with iodine.
AB  - The effect of the adjacent amino acid side chain groups on the iodination rate of
      the tyrosine was studied. The model peptides used were Gly-Tyr-Gly, Leu-Tyr-Leu,
      Glu-Tyr-Glu, and Lys-Tyr-Lys, in which the tyrosine is sandwiched between two
      hydrophobic, two negatively charged, or two positively charged residues. The
      results show only minor differences in the iodination rate of tyrosine in these
      four peptides. These differences are very small in comparison with those
      previously observed between the tyrosines of kappa Bence-Jones proteins.

PMID- 11452877
TI  - Enzymatic iodination of polypeptides with 125I to high specific activity.
AB  - 1. Lactoperoxidase was extracted from cow milk by a simplified method starting
      with batch-wise adsorption onto GM-Sephadex-50. It was then purified by (NH4)2SO4
      precipitation and isoelectric focusing. This product had an A412 nm/A280 nm ratio
      of 0.8-0.9. 2. Lactoperoxidase together with H2O2 could oxidize carrier-free
      Na125I to "active iodine" with efficiency to iodinate proteins to high specific
      activity. 3. Polypeptide hormones radioiodinated by this technique retained their
      immunological reactivity and were used in radioimmunoassays with good results.

PMID- 11452878
TI  - Flow calorimetry of the sorption of butanols to elastin preparations and
      comparison with surface areas determined by krypton-85 adsorption.
AB  - 1. The apparent surface areas of elastin samples as well as of several other
      fibrous protein preparations (collagen, keratin, polymeric stroma of aorta) were
      determined using two different approaches: (a) the Brunauer-Emmett-Teller method
      with 85Kr and (b) microflow calorimetry with n- and tert.-butanol as adsorbents
      in a heptane stream. 2. Areas of heat signals obtained by flow calorimetry for
      the adsorption and desorption of n- and tert.-butanol were substantially
      equivalent; desorption was more protracted than adsorption, the difference
      between the speed of desorption and adsorption increased with decreasing chain
      length of the alcohols (methanol, ethanol, n-propanol and n-butanol). 3. An
      inverse linear relationship was found between the energy change recorded during
      the adsorption process and the chain length of the alcohols (methanol, ethanol, n
      propanol, n-butanol). 4. Heats of adsorption of tert.-butanol were systematically
      found to be significantly lower than those of n-butanol with all the protein
      samples investigated. 5. The apparent surface areas of the protein samples
      determined with tert.-butanol were on the average of the same order or only
      slightly higher than those obtained with 85Kr. Results obtained with n-butanol
      were significantly higher. The difference between surface areas obtained with n-
      and tert.-butanol depended on the nature of the protein sample, on its method of
      preparation and to some extent on the residual humidity of the sample. 6. The
      results could be explained on the basis of the hydrophobic theory of elastin
      structure (see ref. 4) and confirmed our former conclusions (see ref. 3)
      concerning the significantly higher surface areas of elastin samples purified by
      different procedures as compared to collagen or to keratin. They also confirmed
      the accessibility of the surface of elastic fibers to the molecular probes used
      in the polymeric stroma of aorta.

PMID- 11452879
TI  - Binding of ligands by proteins: a simple method with Sephadex gel.
AB  - A simple procedure for the measurement of ligand binding by proteins was devised
      with Sephadex gel; this procedure differs from the more common method of gel
      filtration.

PMID- 11452880
TI  - Association of lactoferrin with other proteins, as demonstrated by changes in
      electrophoretic mobility.
AB  - Lactoferrin in a number of human body fluids was found to possess different
      electrophoretic mobilities, while being immunologically identical. The isolated
      protein migrated slower than any of the naturally occurring forms. This
      phenomenon was found to be due to the property of human lactoferrin to interact
      strongly with acidic macromolecules, forming complexes with a faster migration
      than the single protein. Beside electrostatic interactions also other forces seem
      to be involved in the complex formation.

PMID- 11452881
TI  - Anomalous behavior or ribonuclease A on Sephadex G-100.
AB  - Ribonuclease A was found to behave in an unusual fashion on a Sephadex gel
      column. Though ribonuclease A produces a single, well-defined protein peak on
      elution, enzyme activity can be detected several void volumes after the protein
      peak. A second unrelated protein added to the column will displace further
      activity as will 0.5 M phosphate buffer. This additional activity, apparently due
      to ribonuclease A or an active fragment of the enzyme, would appear to make this
      enzyme unsuitable for use as a standard in molecular weight determinations of
      other nucleases.

PMID- 11452882
TI  - Conformation of allantoicase in aqueous solution.
AB  - 1. The separation of 0.9-S and 10.8-S allantoicase with the aid of a 2H2O-H2O
      gradient was described. The resulting preparations were subjected to
      sedimentation equilibrium, optical rotatory dispersion (ORD), circular dichroism
      (CD) and infrared studies. 2. The molecular weight of 0.9-S allantoicase was
      determined to be about 1.1 x 10(4) g/mole in studies on the sedimentation
      behavior, the metal content and amino acid composition. The molecular weight of
      10.8-S allantoicase was about 15.4 x 10(4) g/mole. 3. Optical rotatory
      dispersion, circular dichroism and infrared studies indicated that both molecules
      contain alpha-helix, beta conformation and random coil. A Cotton effect at 418 nm
      was ascribed to the asymmetric binding of Mn2+ to the enzyme. Competitive
      inhibitors decreased the absorption and circular dichroism bands at about 280 nm
      and 418 nm. These phenomena suggested that the aromatic groups may play an
      essential role in the binding of substrates and inhibitors by the Mn(2+)-enzyme
      complex. 4. Comparison of alpha-helical contents of metalloallantoicases showed
      that the enzymes with low helical contents exhibited high enzymic activities. 5.
      The nearly identical physicochemical behavior and specific enzymic activity of
      0.9-S and 10.8-S allantoicase indicated that they are very similar in structure
      and conformation.

PMID- 11452883
TI  - The effect of urea and guanidinium chloride on activity of subtilisin Carlsberg.
AB  - As shown by viscosity and optical rotation dispersion measurements, subtilisin
      Carlsberg is not denatured in the presence of 10 M urea or 6 M guanidinium
      chloride. This unusual structural stability made it possible to investigate the
      effects of these hydrophobic-bond breaking solutes on various aspects of the
      enzymic interaction with substrates and inhibitors. The binding of the
      competitive inhibitor N-benzoylarginine was decreased by urea or guanidinium
      chloride. The nature of this effect was such as to implicate hydrophobic
      interaction as making a major contribution to the binding. By contrast, Ks for
      the substrates N-acetyltyrosine ethyl ester, N-benzoylarginine ethyl ester and N
      trans-cinnamoylimidazole was apparently unchanged by the presence of urea or
      guanidinium chloride. The influence of these solutes on kcat for the substrates
      was rather involved. Tentative hypotheses are put forward to account for the
      effects seen.

PMID- 11452884
TI  - Differential molecular sieving permits visualization of hexokinase isoenzymes
      following electrophoretic separation in high resolution acrylamide gels.
AB  - 1. Differential molecular sieving is the concept applied to bring together
      isoenzymes of ATP:D-hexose-6-phosphotransferase (hexokinases) with glucose 6
      phosphate dehydrogenase in acrylamide gels by utilization of their dissimilar
      electrophoretic mobilities. 2. The hexokinase isoenzymes migrate and separate in
      gels with pore sizes selected to entrap glucose 6-phosphate dehydrogenase in
      their interstices. The locations of the bands of specific activity are visualized
      by fluorescence of NADPH under long wave, ultraviolet radiation. 3. A new
      discontinuous electrochemical system has been devised to deliver protective thiol
      groups into the gel. Cysteine (trailing ion) and SO4(2-) (leading ion) form a
      sharp moving boundary. 4. The high resolution of the system has permitted
      visualization of a rapidly migrating, high Km hexokinase in murine spleen, fat,
      kidney and lymph nodes. Hexokinase Types I and II, were observed in all tissues
      tested, but Type IV was seen only in the liver. 5. The importance of glucose
      concentration effects on hexokinase activity is emphasized by inactivation of
      slowly migrating low Km hexokinase Types I and II following exposure to 200 mM
      glucose during preparation of extracts.

PMID- 11452885
TI  - Studies on a rat-liver cell-sap protein yielding 3-[32P]-phosphohistidine after
      incubation with [32P]ATP and alkaline hydrolysis. Identification of the protein
      as ATP citrate lyase.
AB  - 1. The rat-liver cell-sap material from which 3-[32P]phosphohistidine was
      previously isolated after incubation with [gamma-32P]ATP and alkaline hydrolysis,
      was shown to increase about 6-fold on a high-carbohydrate diet. This increase in
      32P labelling corresponded to the increase in ATP citrate lyase activity of
      livers of rats fed on a high-carbohydrate diet, as reported by others. 2. ATP
      citrate lyase [ATP:citrate oxaloacetate-lyase (CoA-acetylating and ATP
      dephopshorylating), EC 4.1.3.8] was purified from rat liver essentially according
      to the method of Plowman and Cleland (J. Biol. Chem., 242 (1967) 4239). The
      purified enzyme was incubated for a short time at 0 degree with [gamma-32P]ATP in
      the presence of 20 mM magnesium acetate. The phosphorylated protein was
      hydrolysed in alkali and the main part of the radioactivity was identified as 3
      [32P]phosphohistidine. The identity of the phosphorylated amino acid was
      established by Dowex-1 chromatography, paper electrophoresis, paper
      chromatography and by analysis of the stability to acid. 3. It is concluded from
      these and previous results from this laboratory that ATP citrate lyase and
      nucleoside diphosphate kinase (ATP:nucleoside diphosphate phosphotransferase, EC
      2.7.4.6) account for most of the normal rat-liver cell-sap protein which is
      rapidly phosphorylated by ATP.

PMID- 11452886
TI  - Enzyme-linked immunosorbent assay. II. Quantitative assay of protein antigen,
      immunoglobulin G, by means of enzyme-labelled antigen and antibody-coated tubes.
AB  - Alkaline phosphatase from calf intestinal mucosa has been conjugated to a protein
      antigen, rabbit IgG. Such conjugates, prepared by glutardialdehyde, have been
      used in a competitive solid phase immunoassay. In this test native antigen
      inhibits the binding of the conjugate to homologous antibodies adsorbed to
      plastic tubes. Using this assay 1-100 ng/ml of the antigen could be determined.

PMID- 11452887
TI  - Physicochemical and immunochemical studies on bovine IgA and glycoprotein-a.
AB  - 1. Bovine secretory IgA (SIgA) from colostrum (mol. wt. about 410,000) is
      composed of four alpha-chains (mol. wt. 61,000), four light chains (mol. wt.
      23,000) and one molecule of glycoprotein-a (mol. wt. 70,000-86,000). The alpha
      chains are antigenically and physicochemically distinct from the heavy chains of
      IgM, IgG1 and IgG2 while the light chains are identical to those occurring on
      other bovine immunoglobulins. Glycoprotein-a and bovine free secretory component
      are identical and the former name should be abolished. Much of this protein is
      covalently bonded to IgA. 2. The gel filtration behavior of serum IgA suggests it
      is a dimer. 3. The elution behavior of IgA and SIgA from ion-exchange columns and
      the solubility characteristic of SIgA in the presence of Zn2+ are similar to
      those of human and rabbit IgA. 4. The disc electrophoretic behavior of IgA and
      SIgA are distinct from IgM, dimeric IgG1, 7-S IgG and glycoprotein-a. Dimeric
      IgG1 (s20,w = 9.5) is abundant in colostrum and is similar in size to SIgA. 5.
      Bovine IgA shows physicochemical and immunochemical heterogeneity when studied by
      gel filtration, disc electrophoresis, immunoelectrophoresis and
      ultracentrifugational analyses. Lacrimal and nasal SIgA possess antigenic
      determinants absent on colostral SIgA.

PMID- 11452888
TI  - Isolation and immunochemical studies of dog trypsin.
AB  - Dog trypsin (EC 3.4.4.4) was isolated from dog pancreatic juice on SP-Sephadex C
      50. The preparation was homogeneous on disc electrophoresis at pH 4.3. On agarose
      gel electrophoresis at pH 8.6, dog pancreas trypsinogen had the mobility of an
      alpha 2-globulin and trypsin the mobility of a beta-globulin. On gel filtration
      on Sephadex G-75 at pH 4.0, dog trypsin was eluted in the same fractions as
      bovine trypsin. It was inhibited by soybean trypsin inhibitor. Rabbit anti-dog
      trypsin inhibited the caseinolytic activity of bovine trypsin by about 60%.

PMID- 11452889
TI  - [Comparison of the proteins in pancreatic juice in normal and diseased humans.
      Determination of serum proteins and demonstration of a particular protein in
      chronic calcifying pancreatitis].
AB  - For a better understanding of the molecular mechanism leading to intraductal
      precipitation of proteins in primary chronic calcifying pancreatitis in man, we
      studied the composition of normal and pathological human pancreatic juice by
      immunotechniques. We found an increased level of serum proteins in pathological
      juices: 12.47% of total proteins compared to 1.8% in normal ones; albumin is
      8.16% of the total proteins, IgG 2.84%, IgA 0.83% and IgM 0.91%. Transferrin and
      alpha 2-macroglobulin are present, but were not estimated. The albumin/IgA and
      albumin/IgG ratios favour the hypothesis of a local synthesis of these
      immunoglobulins as was shown in normal juice. The cross adsorption of antisera
      against pancreatic juice showed the presence in the pathological juice of a
      normal molecule in much higher concentration. The role of these proteins in
      precipitation is discussed.

PMID- 11452890
TI  - The effect of 2H2O on the quaternary structure of the fatty acid synthetase
      multienzyme complex.
AB  - The effect of 2H2O on the cold-induced dissociation and cold-induced inactivation
      of fatty acid synthetase from lactating mammary gland has been studied. The rate
      constants for these reactions were almost identical and were lowered in media
      containing 2H2O. The results have been interpreted to indicate that inactivation
      of the enzyme in the cold is a direct result of dissociation into subunits and
      that maintenance of the native structure of the enzyme is limited by the strength
      of hydrophobic bonds.

PMID- 11452891
TI  - The myoglobin of primates. I. Hylobates agilis (gibbon).
AB  - The myoglobin of a gibbon has been compared with that of man. There was only one
      difference, residue 23 (B4) which is Gly in man was found to be Ser in the
      gibbon. Two corrections have also been made to the previously published sequence
      of human myoglobin (A.E. Romero Herrera and H. Lehmann, Nature, New Biol., 232
      (1971) 149).

PMID- 11452892
TI  - [Significance of the uPA/uPAR system for development of arteriosclerosis and
      restenosis].
AB  - Arteriosclerosis and the development of restenosis still remain a significant
      clinical problem. Migration of vascular smooth muscle cells from the media to the
      intima and cell proliferation are the hallmarks of the underlying
      pathomechanisms. Cell migration requires chemotaxis, phenotypic changes of cells,
      cell adhesive and de-adhesive events and the coordinated remodeling of the
      extracellular matrix. One of the phenotypic changes induced in migrating cells is
      the increased expression of urokinase plasminogen activator (uPA) and of its
      specific receptor uPAR. They are polarized to the leading edge of migrating
      cells. Both uPA and uPAR are key mediators of extracellular proteolysis. They
      participate in extracellular matrix remodeling, activate cells and enable them to
      migrate and invade into different tissue layers. UPA/uPAR are multifunctional
      proteins influencing a great variety of signal transduction pathways ultimately
      culminating in the regulation of cell migration and proliferation. In addition to
      time- and space-confined proteolysis this powerful system can mediate chemotaxis,
      cell adhesion and gene expression, partly by interacting in concert with
      integrins, G proteins, or with yet unidentified coreceptors or adapter molecules.
      Interaction with the uPA/uPAR system or components of its specific signal
      transduction pathways may serve as a guide for the development of effective
      therapeutic strategies to prevent arteriosclerosis and restenosis after
      percutaneous arterial angioplastic interventions.

PMID- 11452893
TI  - [Gregg phenomenon and garden hose effect].
AB  - Under physiologic circumstances, cardiac function determines myocardial oxygen
      consumption and consequently coronary perfusion. Surprisingly, in a reverse
      direction, improved coronary perfusion also increased myocardial oxygen
      consumption and contractile function. This experimental finding, now 40 years
      old, is termed the Gregg phenomenon. Some 10 years later, in experiments by
      Arnold and co-workers, an isolated increase in perfusion pressure improved
      ventricular function. In this context, the term 'gardenhose effect' was coined,
      implying a hydraulic explanation of the Gregg phenomenon. In the following, we
      attempt to distinguish the Gregg phenomenon from the gardenhose effect and to
      critically evaluate them.

PMID- 11452894
TI  - [The site and extent of arteriosclerosis. Comparative planimetric studies of the
      left descending coronary artery, internal carotid artery, superficial femoral
      artery and abdominal aorta in 104 cadavers].
AB  - BACKGROUND: Arteriosclerosis is generally considered to be a generalized disease,
      involving different vascular regions to approximately the same extent. PATIENTS
      AND METHODS: In order to assess the extent of ateriosclerosis quantitatively, all
      arteriosclerotic lesions and additionally the complicated (calcified, ulcerated,
      thrombosed) arteriosclerotic lesions of the abdominal aorta, the superficial
      femoral arteries, the left descending coronary artery and the internal carotid
      arteries were measured by planimetry in 102 autopsies (64 male, 38 female; mean
      age: 62 +/- 16 years). RESULTS: Arteriosclerosis increased with age. The overall
      extent of arteriosclerotic lesions of each artery was classified to one of the
      following 4 degrees of intimal involvement (0-25, 26-50, 51-75%, 76-100%). When
      comparing the 4 different vascular regions of each patient we found maximal
      deviations by 1 degree in 34%, by 2 degrees in 41% and by 3 degrees in 20%. In
      only 5% of the patients studied were all arteriosclerotic lesions of the same
      degree. In order to analyze the complicated plaques 7 degrees were used (intimal
      involvement: 0, 1-10, 11-20, 21-30, 31-40, 41-50% and > 50%). In 14 patients we
      found no complicated plaques. The remaining 88 showed complicated lesions in at
      least 1 vascular region. Deviations by 1 degree were found in 22%, by 2 degrees
      in 32%, and by 3 or more degrees in 46%. In the paired arteries (carotid,
      femoral) there were no significant differences comparing the mean values of the
      extent of arteriosclerotic lesions on the right and left side. In many cases,
      however, remarkable intraindividual differences occurred. Patients with main risk
      factors usually had more pronounced arteriosclerotic lesions than those without.
      In patients who died from coronary artery disease the extent of arteriosclerotic
      lesions was also usually larger in the other vascular regions as compared to
      those patients who died from other reasons. Comparing postmortem and intravital
      extent of arteriosclerotic lesions some peculiarities of postmortem specimens
      should be considered. CONCLUSIONS: A uniform involvement of all vascular regions
      by arteriosclerosis occurs only rarely. Considerable intraindividual differences
      are the rule and a severe, generalized uniform affection is an exception. This,
      however, does not exclude in patients with severe arteriosclerosis of one region
      that a larger involvement of other vascular regions may also occur, as this was
      found for patients with severe arteriosclerosis in coronary arteries. Regarding
      the extent of arteriosclerosis there are artery- and additional localization
      specific features.

PMID- 11452895
TI  - [Clinical diagnosis of acute aortic dissection].
AB  - Despite the availability of modern imaging technology, 35% of aortic dissections
      remain undiagnosed in vivo because clinical criteria for aortic dissection are
      not available to date. The present study analyzed 250 patients with acute chest
      and/or back pain, absence of an established differential diagnosis of the pain
      syndrome and clinical suspicion of acute aortic dissection for presence of 26
      clinical variables. Multivariate analysis identified an aortic pain syndrome with
      immediate onset and/or tearing or ripping character (P < 0.0001), mediastinal
      and/or aortic widening on chest radiography (P < 0.0002) and pulse- and/or blood
      pressure differentials (P < 0.0001) as predictors of acute aortic dissection.
      Probability of dissection was low (7%) with absence of all three variables,
      intermediate (31 and 39%, respectively) with isolated findings of "aortic pain"
      or "mediastinal widening", and high (> 83%) with either isolated "pulse- and/or
      blood pressure differentials" or any combination of the three variables. This
      model appears useful to improve selection of patients for emergency imaging of
      the thoracic aorta.

PMID- 11452896
TI  - [Does early high dosage dipyridamole in prevention of secondary stroke induce
      cardiac events?].
AB  - In a post hoc analysis of the European Stroke Prevention Study 2 (ESPS2), we
      investigated whether dipyridamole given as antiplatelet drug in patients with TIA
      or stroke increases the risk of cardiac events. ESPS2 was a secondary prevention
      trial including 6602 patients with TIA or stroke. Patients were randomized into
      one of four treatment arms: 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg slow
      release dipyridamole (DP), the combination of DP and ASA and placebo. DP did not
      result in a higher number of cardiac events, e.g., angina pectoris, myocardial
      infarction or death. The combination of ASA plus DP was superior to either drug
      alone in the prevention of strokes.

PMID- 11452897
TI  - [Coronary risk profile in women with angiographically normal coronary arteries or
      initial coronary arteriosclerosis].
AB  - The pathophysiology and prognosis of coronary heart disease in women are the
      subject of intensive epidemiological and clinical investigations due to sex
      specific considerations. We have estimated the prevalence of modifiable coronary
      risk factors in 36 consecutive women (mean age 59.7 years) with suspected
      coronary heart disease in whom coronary angiography was performed due to unclear
      chest pain. Seventeen women revealed angiographically normal coronary arteries
      (gr. I) and 19 women showed coronary vessels with initial arteriosclerosis
      (luminal diameter reduction < 35%) (gr. II). Mean age was 59.1 years in gr. I and
      60.3 years in gr. II (p = ns). No woman received lipid lowering drugs within the
      last 6 months. A hormone replacement therapy was not performed in any case. Women
      in gr. I showed significantly higher total and LDL cholesterol levels (271.6 +/-
      34.3 vs 243.5 +/- 44.8 mg/dl; p < 0.005 and 190.5 +/- 36.8 vs 149.7 +/- 45.1
      mg/dl; p < 0.025, respectively) and significantly lower HDL cholesterol values
      (57.8 +/- 16.5 vs 72.8 +/- 19.1 mg/dl; p < 0.0125) compared to women in gr. II.
      The total/HDL cholesterol ratio was 3.6 +/- 1.2 in gr. I and 5.1 +/- 1.7 in gr.
      II (p < 0.005). The positive predictive value for the existence of initial
      coronary atherosclerosis and a total cholesterol/HDL ratio > 4 was 76.5%. The
      negative predictive value and a ratio < 4 was 81.3%. Women in gr. I revealed 1.2
      +/- 0.9 and in gr. II 1.6 +/- 0.8 risk factors (smoking, hypertension, body mass
      index > 30 kg/m2, diabetes mellitus, hyperlipidemia) (p < 0.10). The 10-year risk
      for the occurrence of a coronary event was 9.1 +/- 3.7% in gr. I and 14.2 +/-
      5.8% in gr. II (p < 0.005). The positive predictive value for the existence of
      initial coronary atherosclerosis and a 10-year risk > 10% was 90%. The negative
      predictive value and a 10-year risk < 10% was 64.0%. Our investigation indicates
      that women with a mean age of 60 years, unclear chest pain and without exercise
      induced ischemia are highly suspected to have initial coronary arteriosclerosis,
      when a distinct risk factor profile and a 10-year cardiac event risk > 10% are
      present. For this high risk group of women, intensive secondary prevention
      measures are necessary.

PMID- 11452898
TI  - [Papillary muscle rupture after mitral valve replacement with preservation of
      subvalvular structures].
AB  - We report a female patient with mitral valve replacement and preservation of
      subvalvular apparatus in which parts of the papillary muscle ruptured
      postoperatively. During systole the ruptured papillary muscle prolapsed through
      the native aortic valve. Echocardiographic documentation and operative procedure
      were demonstrated.

PMID- 11452899
TI  - [Acute left heart failure after interventional occlusion of an atrial septal
      defect].
AB  - Congestive left ventricular failure after surgical closure of an atrial septal
      defect (ASD) has been repeatedly reported, particularly in the elderly. We
      present a case of left ventricular failure after a successful transcatheter
      closure of an ASD, which to our knowledge has not been described before. In a 78
      year-old woman (50 kg, 160 cm) with well-preserved left ventricular function
      (ejection fraction 65%) and without coronary artery disease or arterial
      hypertension, an ASD (Qp/Qs 1.6:1) was closed with an Amplatzer Septal Occluder
      without a residual shunt. Two hours after the procedure, she developed pulmonary
      edema due to left ventricular failure (increase of end-diastolic diameter from 42
      mm to 54 mm, ejection fraction 20%), had to be mechanically ventilated for 24
      hours and needed catecholamines for 4 days. High doses of diuretics were supplied
      until the ejection fraction normalized (32%). The patient could not be discharged
      until two weeks after intervention. A reduced preload for decades may predispose
      acute left ventricular failure, particularly in the elderly with compromised
      ventricular compliance.

PMID- 11452900
TI  - [Guidelines for equipping and managing heart catheter rooms (1st revision).
      Issued by the governing body of the German Society of Cardiology-Heart and
      Cardiovascular Research. Revised by order of the Committee of Clinical
      Cardiology].

PMID- 11452901
TI  - Genetic predisposition to periodontitis in children and young adults.

PMID- 11452902
TI  - Health promotion and behavioral approaches in the prevention of periodontal
      disease in children and adolescents.

PMID- 11452903
TI  - Diagnosis and management of periodontal diseases in children and adolescents.

PMID- 11452904
TI  - Epidemiology of periodontal disease in children and adolescents.

PMID- 11452905
TI  - Microbiology of periodontal disease in children and young adults.

PMID- 11452906
TI  - Etiopathogenesis of periodontitis in children and adolescents.

PMID- 11452907
TI  - Periodontal disease in children and adolescents: introduction and classification.

PMID- 11452908
TI  - Influences of systemic diseases on periodontitis in children and adolescents.
AB  - Systemic diseases affecting the host response as primary immunodeficiencies or
      secondary defects caused by lack of nutrients or changes in the local tissues are
      very often accompanied by early-onset prepubertal periodontitis. Local treatment
      in combination with systemic antibiotics may in milder forms improve the
      situation, but in many cases the success is questionable and premature loss of
      teeth occurs. Since the genetic basis of many of the diseases has been
      identified, future developments permit the correction of at least some of these
      defects by gene therapy.

PMID- 11452909
TI  - [Immunophenotype characteristics of blood lymphocytes in patients with
      lymphogranulomatosis].
AB  - The blood lymphocyte immunophenotype was studied in patients with
      lymphogranulomatosis including those having been exposed to the Chernobyl
      spectrum radionuclide radiation in the doses up to 75 sGy. It is shown that in
      both groups of patients, there tends to be a decline in indices for T- and EK
      cell immunity, that comes to be the most apparent in radiation-associated
      lymphogranulomatosis. The data obtained provide scientific explanation of more
      aggressive course of the disease in such patients and of difficulty in treatment.

PMID- 11452910
TI  - [Mineral ions K(+), Na(+), Ca(2+), and Mg(2+) in etiology and pathogenesis of
      arterial hypertension].

PMID- 11452911
TI  - [Risk assessment for development of sudden cardiac death in patients with
      progressive angina (based on results of 4-year prospective study)].
AB  - In a 4-year follow-up of those patients having survived progressive angina (PA),
      the incidence rate was estimated of development of sudden cardiac death (SCD),
      with the aid of the Caplan-Mayer method and that of life tables. SCD rate has
      come to be 21.4% and 7.2% in the main group and that of patients free from
      structural affection of the myocardium. It is during the first year of the follow
      up that patients with prior PA were at the greatest risk for SCD. It has been
      ascertained that aneurysm of the left ventricle and presence of chronic I-II
      degree cardiac insufficiency are independent and significant risk factors for SCD
      in those patients with history of PA.

PMID- 11452912
TI  - [Clinical patameters associated with oxygen-dependent metabolism in neutrophils
      in patients with systemic lupus erythematosus and leukocytopenia].
AB  - The article presents results of examination designed to study parameters
      characterizing the peripheral blood neutrophils functional activity in
      leukocytopenia in patients with diffusive disorders of the connective tissue
      (systemic lupus erythematosus and rheumatoid arthritis), with the above values
      having come to be used in the assessment of severity of the course, differential
      diagnosis of complications, and prognostication of the condition. Such
      cytochemical indices as activity of myeloperoxidase, amounts of cationic
      proteins, capability of neutrophils to reduce nitroblue tetrazolium to
      diphormazine (NBT-test) are considered to be of much informative value which have
      come to be widely used in the diagnosis and prognosis of a great many of various
      medical problems. Defects in neutrophils are shown, disturbances are pointed out
      in their functional activity evidenced by the decline in their capability of
      reducing NBT. Poststimulation metabolic activity is but inadequately increased as
      compared to results in the control group. Of practical value is screening of
      patients presenting with low values for the functional reserve of heterophilic
      leucocytes, the purpose of which screening being early prognostication of the
      course of pyo-inflammatory complications.

PMID- 11452913
TI  - [The liver hemodynamics in portal gastropathy].
AB  - Complex hemodynamic studies were made in 280 patients with hepatic cirrhosis
      presenting with the portal hypertension syndrome. It has been found out that the
      isolated hyperdynamic state of blood circulation in the upper portion of the
      stomach is responsible for the development of not only portal gastropathy but
      gastric varicosity as well. Revealed in the above patients was a decline in the
      arterial and portal bloodflows corresponding to a diminution of total hepatic
      bloodflow in which the share of the portal versus arterial bloodflow tended to be
      on the increase. In portal gastropathy the portoarterial ratio gets changed at
      the presinusoid and sinusoid levels so that the predominance of the portal flow
      into the liver over the arterial inflow is associated with the predominance of
      the arterial component over the venous one in the sinusoid bloodflow.

PMID- 11452914
TI  - [Methodological approaches toward higher safety of hemotransfusion therapy].
AB  - Safety of haemotransfusions remains a challenge in modern transfusion medicine.
      Methodological approaches toward eliminating risks for haemotransfusion
      complications include a wider employment of principles of haemocomponent therapy,
      prevention of a possibility of infections contamination of blood and its
      components, deleukocytation of blood components, categorizing of donors by
      phenotypes, registering those donors having been phenotyped, categorizing of
      potential recipients by phenotypes, screening of alloimmune antierythrocytic
      antibodies in donors, sick and pregnant women, introduction of autodonation on a
      wide scale.

PMID- 11452915
TI  - [Oxidation-reduction processes in patients with recurring nephrolithiasis
      complicated with chronic pyelonephritis and urostasis during combined treatment].
AB  - Results of study into the condition of reduction-oxidation processes, in
      particular of those associated with generation of the superoxide radical, are
      submitted together with those of determination of levels of inorganic phosphate
      which is known to be an important indicator of the tissue bioenergy potential, in
      112 patients presenting with a recurring form of nephrolithiasis exposed to a
      multiple-modality treatment that included conventional antiinflammatory and
      antibacterial therapy plus "open" and endourological operations on kidneys and
      ureters. The multiple-modality treatment of the main group patients was
      supplemented with phlogenzyme, a drug of II generation systemic enzymotherapy. An
      enhanced generation of superoxide radical was recordable having developed in the
      wake of a steady increase in the activity of xanthinoxidase. The authors have
      come to the conclusion that the conducted therapeutic intervention, especially as
      part of systemic enzyme therapy, results in decline of activity of the xanthine
      oxidation processes and brings about a change in the blood:urine inorganic
      phosphate concentrations ratio.

PMID- 11452916
TI  - [Clinical manifestations of delayed sequelae of closed craniocerebral injuries in
      patients of older age].
AB  - Disclosed in the remote period in patients at older ages, who had survived closed
      craniocerebral injury (CCCI) were asthenic, liquorohypertensive, vestibular
      syndromes, posttraumatic encephalopathy, epileptoid syndrome, all of which are
      manifestations of traumatic condition of the brain. It is the premorbid state
      together with the presence of concomitant somatic conditions including the
      vascular factor that are believed to play a major part in the formation of
      delayed sequence. CCCI is considered to be a factor promoting the origination and
      aggrevation of the existing chronic somatic conditions. Hence, CCCI and its
      sequelae can be regarded as a risk factor for vascular diseases.

PMID- 11452917
TI  - [Anti-inflammatory activity and toxicity of KhTM preparation].
AB  - The studies made suggest XTM to be endowed with an apparent antiexudative and
      antiproliferative activities superior to current non-steroidal antiinflammatory
      agents. Taking into account the above drug's low activity, wide spectrum of its
      therapeutic action, it will, we believe, come to be widely used as an effective
      antiinflammatory remedy.

PMID- 11452918
TI  - [Characteristics of the thyroid system in adolescents with the autonomic and
      vascular disfunction of the hypotensive type].
AB  - As many as 185 juveniles presenting with hypotensive type vegetative-and-vascular
      dysfunction (VVD), their age ranging between 11 to 14 years, were studied for
      functional activity of their thyroid system. The control group comprised 69
      healthy children at the same age. The study made showed the VVD adolescents'
      hypophyseal-and-thyroid system to be compromised. High thyroid activity in the
      above patients was found to be the case in the presence of normal values for the
      thyrotropic function of the pituitary body. The revealed specificities were more
      manifest in VVD boys and suggest to us a compensatory reaction of the thyroid
      system in response to the development of circulatory hypoxia secondary to
      disturbances in the vegetative control of the cardiovascular system activity.

PMID- 11452919
TI  - [Blood plasma level of insulin and sensitivity to it in tissues of patients with
      newly detected diabetes mellitus type II].
AB  - Type II diabetes mellitus is the most common type of the condition. But little is
      yet known about mechanisms responsible for its development in persons with
      different body masses. We studied blood plasma levels of insulin and assessed
      sensitivity to it in 32 patients with freshly detected type II diabetes mellitus
      with normal and above normal body weight. Of these, 20 subjects were obese, the
      other 12 being not fat; the control group comprised 30 persons obese and non
      obese, with n = 15 and 15 respectively. Recordable in patients was a marked
      elevation of blood plasma level of insulin accompanied by decrement of the
      peripheral tissue sensitivity to it in obese diabetic patients while in those
      persons with normal body mass there was a substantial reduction in the production
      of insulin, which differences may indicate different pathogenesis of development
      of type II diabetes mellitus in persons with different body masses.

PMID- 11452920
TI  - [Combined hormone therapy in hyperplasia of the endometrium].
AB  - The combined hyperplastical endometrial processes are very common pathology. In
      spite of noticeable achievements in hormonotherapy to treat the above trouble the
      recurrence rate comes up to as high as 45%. The recurrent combined hyperplastical
      endometrial processes prophylaxis with making use of the intrauterine system with
      levonorgestrel "Mirena" has been shown to be effective, with the above-mentioned
      system having been inserted on completion of the 6-month course of treatment with
      orgametryl.

PMID- 11452921
TI  - [Hemomorphological and ultrasonic methods in diagnostics of the fetoplacental
      system status in premature labor].
AB  - In ultrasonic and histohemomorphological investigations designed to study the
      status of the fetoplacental system in premature delivery associations have been
      demonstrated between these and adverse impact on the state of the intrauterine
      fetus. The placental vascular reactions pathological state may be a factor in the
      induction of preterm labor.

PMID- 11452922
TI  - [Hypoxia, lipid peroxidation, and defence antioxidant system in children born to
      mothers with extragenital pathology].
AB  - A study was made on the condition of lipid peroxidation and of the antioxident
      system of defence in 20 infants born to healthy mothers (control group), 12
      babies born to mothers with diabetes mellitus, 15 infants born to mothers with
      neurocirculatory asthenia and 12 infants born to mothers with congenital heart
      diseases. In infants born to mothers with diabetes mellitus and cardiovascular
      pathology, the system of regulation was found to have gotten out of balance, the
      compensatory-and-adaptive reactions upset. Accumulation of peroxidic products and
      depletion of the antioxidant system of defence tended to be more readily seen in
      those babies born to mothers with diabetes mellitus. The results secured attest
      to the need for employment of drugs endowed with antioxidant activity.

PMID- 11452923
TI  - [Characteristics of the clinical course of ischemic heart diseases in patients
      with hypertensive dyscirculatory encephalopathy].
AB  - Association of ischemic heart disease (IHD) with vascular affections of the brain
      is the cardiocerebrovascular syndrome having common pathogenetic mechanisms of
      formation in the structure of cardiovascular pathology. Some specificities were
      studied of the clinical course of IHD concomitant with hypertensive
      dyscirculatory encephalopathy (HDE) in 35 patients (main group), with 25 IHD
      controls free from manifestations of neurological symptomatology. In IHD HDE
      patients the anginous syndrome is characterized by a lesser dependency on time in
      each period of 24 hours and physical load and greater dependency on arterial
      pressure, meteofactors, it is often accompanied by cephalgia appearing with the
      intake of antianginal drugs, dizziness, memory, sleep disturbances. The main
      group patients demonstrated elevated levels of LPO products, those of lipid
      metabolism, and the AO system tension.

PMID- 11452924
TI  - [Determination of index of the transcutaneous electrostimulation effect on the
      liver and bile ducts based on micellar structure and lithogenicity of bile in
      patients with the exterior drainage of the common duct].
AB  - Kept under clinical observation were 78 patients under common bile duct drainage
      for mechanical jaundice of the nontumor genesis. In all patients, micellarity and
      lithogenicity of the hepatic bile (fraction "C") were studied postoperatively,
      with an individual selection having been carried out of the index of
      transcutaneous electrostimulation effect on the hepatobilliary system. An
      effective modality has been elaborated for treatment and prophylaxis of hepatic
      insufficiency, correction of micellarity and lithogenicity of bile in the early
      postoperative period in patients with mechanical jaundice of the nontumor
      genesis, that can be recommended for use in the health care practice.

PMID- 11452925
TI  - [Effect of smoking and alcohol drinking on the moisture-excreting lung function].
AB  - A study was made on the moisture-exuding function of the lungs in healthy persons
      who smoke and in patients with different forms of tuberculosis, who abuse and do
      not abuse alcohol. It has been ascertained that the moisture-exuding function of
      the lungs is time-related, dynamic and changeable, and dependent upon certain
      environmental factors. Smoking and alcohol enhance the moisture-exuding function
      of the lungs, secondary to which fact they can be regarded as those factors
      facilitating the development of pathological processes in the lungs, tuberculosis
      included.

PMID- 11452926
TI  - [Enhancement of efficacy of neoadjuvant polychemotherapy in combined treatment of
      lung cancer].
AB  - It is not infrequently that the known preoperative chemotherapy options come to
      be not very effective in the treatment of patients with pulmonary cancer by
      reason of a fraction of chemoresistant tumour cells. To enhance effectiveness of
      treatment we attempted preoperative thermochemotherapy. As many as 62 patients
      with pulmonary cancer were exposed preoperatively to a 40-minute r. f.
      hyperthermia plus chemotherapy. All these underwent radical surgery. The above
      method of neoadjuvant treatment permitted increasing significantly the 3-year
      survival of those patients presenting with locally spread pulmonary cancer.

PMID- 11452927
TI  - [The Lecompte surgical procedure in transposition of great vessels].
AB  - The article presents the first experience gained with the use of the Lecompt
      operation in eleven patients presenting with transposition of the great vessels,
      ventricular septal defects, and pulmonary artery stenosis. The above procedure
      had been performed during the period 1995-1998, with the short-term and remote
      results having been analyzed. A detailed description is given of the surgical
      technique. The Lecompt procedure was found to be superior to the Rastelli
      operation.

PMID- 11452928
TI  - [Acute pyelonephritis associated with intestinal dysbacteriosis: incidence and
      enhancement of efficiency of treatment].
AB  - A study was made on the incidence rate of acute pyelonephritis associated with
      intestinal dysbacteriosis in urological patients (n = 68). Prehospitalization and
      precombined-treatment duration of the illness came up to one to four days. It has
      been ascertained as a result of the conducted study that under present ecological
      conditions, acute pyelonephritis runs its course in the presence in patients of
      dysbacteriosis of the intestines even before the start of treatment in an
      urological clinic setting. Antibacterial treatment of patients with acute
      pyelonephritis without simultaneous action on the pathogenic intestinal
      microflora and normalization of colonizing normoflora was found to produce
      profound aggravation of dysbacteriosis and to result in the development of
      candidasis. Extermination with the aid of the intestinal antibiotic intetrix of
      the pathogenic microflora in the intestines together with achieving of
      normalization of intestinal normoflora by way of the enteral intake by patients
      with acute pyelonephritis of eubiotics permit the marked improvement to be
      achieved in results of combined treatment thereof.

PMID- 11452929
TI  - [Individual selection of the total dose of laser energy in percutaneous laser
      disk nucleotomy].
AB  - On the basis of studies on concentration and mobility of ions in the solution
      (conductometry technique) an individual selection is suggested of the total dose
      of laser energy during the percutaneous laser disk nucleotimy sessions. The
      conductometry technique permits arriving at an objective decision on both
      completion/continuation of the operation and change in the laser energy rate.

PMID- 11452930
TI  - [Psychopharmacotherapy in combine treatment of depressive disorders in patients
      with brain pathology affected by the Chernobyl Atomic Electric Power Station
      accident].
AB  - The studies made showed that employment of amitriptylinum in patients presenting
      with depressive disturbances against the background of the organic affection of
      the brain resulted in origination od side effects, which fact failed to promote
      the reduction of depressive symptomatology. The use of azaphenum is not very
      effective. Protiadenum, a new antidepressant, does not induce side effects like
      amitriptylinum and was noted to be more effective than azaphenum. Protiadenum
      combined with nootropil and those drugs improving cerebral microcirculation
      (cavintonum) enhance efficiency of psychopharmacotherapy of depressive disorders
      in persons with organic affection of brain, who had become victims of the
      Chernobyl accident, which fact permits recommending such therapy in the complex
      of curative measures in the given contingent of patients.

PMID- 11452931
TI  - [Role of the iodine microelement in nutrition and prophylaxis of various
      diseases].
AB  - The article describes various iodine deficiency-related disorders. Iodine
      deficiency is the chief cause of goiter, mental retardation and other disorders.
      It is an acute problem the whole mankind face, Ukraine included. In this country,
      the following territories are biogeochemical provinces: Zhitomir, Lvov, Ternopol,
      Volyn regions and other regions of Ukraine, and some regions of the Crimea as
      well. It is necessary that food rations be supplemented with different iodine
      preparations with the view of preventing iodine deficiency. Concentrates of food
      fibre recovered from cell walls of various plant raw stuff and containing
      complexes of structural carbohydrates and lignin can be used in combination with
      iodine compositions in dealing with the above problem.

PMID- 11452932
TI  - [Erroneous diagnosis of myocardial infarction in acid poisoning].

PMID- 11452933
TI  - Cytogenetic abnormalities in 42 rhabdomyosarcoma: a United Kingdom Cancer
      Cytogenetics Group Study.
AB  - BACKGROUND: Rhabdomyosarcomas are the most common type of pediatric soft tissue
      sarcoma. The cytogenetic literature on RMS is biased towards the less common
      alveolar subtype (ARMS), which is frequently associated with specific
      translocations and the PAX3/7-FKHR fusion genes. Relatively few karyotypes are
      reported for the embryonal subtype (ERMS). The aim of this study was to further
      cytogenetic knowledge of RMS subtypes. PROCEDURE: Representative examples of all
      karyotypes from UKCCG; member laboratories were reexamined and their
      histopathologies reviewed through the United Kingdom Children's Cancer Study
      (Group) (UKCCSG). Molecular evidence for the PAX3/7-FKHR fusion genes was
      available for five ERMS and seven ARMS cases and compiled with the karyotypes.
      RESULTS: Clonal chro mosome aberrations were characterized for 25 ERMS and 17
      ARMS cases. Thirty-six percent of the ERMS cases involved translocation
      breakpoints in the 1p11-q11 region. Ten of the seventeen cases of ARMS showed
      cytogenetic evidence for the t(2;13)(q35;q14), consistent with molecular data
      available from four of these. Two further ARMS cases revealed a PAX3-FKHR and a
      variant PAX7-FKHR fusion gene product that were not detected cytogenetically.
      CONCLUSIONS: Many of the karyotypes from both subtypes were complex. The frequent
      involvement of the 1p11-1q11 region and gain of chromosomes 2, 8, 12, and 13 in
      ERMS may be functionally significant. There was no evidence for involvement of
      the PAX3/7-FKHR genes in ERMS, and cryptic involvement was found in some ARMS.
      There were no consistent chromosomal rearrangements associated with apparently
      translocation negative ARMS cases.

PMID- 11452934
TI  - Prognostic significance of Ki-67 (MIB-1) proliferation index in childhood
      primitive neuroectodermal tumors of the central nervous system.
AB  - BACKGROUND: Primitive neuroectodermal tumors (PNET) of the central nervous
      system, including medulloblastomas, are the most common malignant brain tumors of
      childhood. Whereas some patients experience prolonged disease control after
      surgery and adjuvant therapy, others with tumors that appear comparable will
      relapse and eventually die from progressive disease. PROCEDURE: Because
      proliferative activity may provide a potential correlate of biologic
      aggressiveness, PNETs of 78 well-characterized patients were evaluated by Ki-67
      (MIB-1) immunohistochemistry. Proliferation indices (PI) were determined by
      counting Ki-67 (MIB-1) positive tumor cells either in the highest staining region
      (hot spot PI), or in at least 15 randomly chosen fields (random PI). RESULTS:
      Twenty-five of 78 PNETs showed amore than twofold higher value of hot spot PI
      (median 9.3%; range 0.6-56%), compared to random PI (median 5.6%; range 0.2
      41.3%), Univariate Cox regression analysis revealed that PNETs with a high hot
      spot PI had a significantly greater risk of progression and death than PNETs with
      a low hot spot PI (hazard ratio 1.58, P = 0.04). The hazard ratio remained
      significant after adjusting for M-stage in multivariate analysis. In contrast to
      hot spot PI, random PI proved not to be a significant prognostic predictor.
      CONCLUSIONS: Hot spot PI is a significant and independent prognostic factor in
      PNETs. Its assessment is uncomplicated, reliable, and may supplement routine
      histologic examination as a means for improving the accuracy of predicting the
      biologic behavior of childhood PNETs.

PMID- 11452935
TI  - Risk factors for pediatric tumors of the central nervous system: results from a
      German population-based case-control study.
AB  - BACKGROUND: From 1993 to 1997 we conducted two population-based case-control
      studies on childhood cancer and a variety of potential risk factors in Germany.
      One case group involved children under the age of 15 years having a tumor of the
      central nervous system (CNS). PROCEDURE: For both studies, one conducted in the
      northwestern area of Germany, the other covering the whole of West Germany,
      incident cases were identified from the nationwide German Childhood Cancer
      Registry, and controls were randomly selected from complete population
      registration files. RESULTS: In total 466 pediatric CNS tumor cases and 2,458
      controls were available for analyses. We observed only few positive associations,
      namely, between CNS tumors and low birth weight [<2,500 g; odds ratio (OR), 1.73;
      95% confidence interval (CI), 1.06-2.84], between ependymoma and maternal smoking
      during pregnancy (>10 cigarettes per day: OR, 4.71; 95% CI, 1.69-13.1), and
      between astrocytoma and exposure to wood preservatives (OR, 1.91; 95% CI, 1.22
      3.01). CNS tumors were not associated with high birth weight, duration of breast
      feeding, maternal age at time of delivery, duration of gestation, previous fetal
      losses, paternal smoking during pregnancy, maternal alcohol consumption, the
      child's exposure to pesticides, maternal diagnostic X-ray examinations during
      pregnancy, X-ray examinations of the child, or exposure to residential magnetic
      fields. CONCLUSIONS: Despite the large study population, we found only few
      factors that were associated with CNS tumors or one of the morphological
      subgroups. Therefore, our results suggest that aspects of the prenatal and
      neonatal period play only a minor role in the etiology of pediatric CNS tumors.

PMID- 11452936
TI  - Intact T-cell regenerative capacity in childhood acute lymphoblastic leukemia
      after remission induction therapy.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is a bone marrow disease. This may
      adversely affect the capacity of T cells to recover from chemotherapy-induced T
      cell depletion and thus contribute to the prevailing immune deficiency in ALL
      patients. PROCEDURE: We tested the capacity of T-cells to regenerate in 18 ALL
      children in first clinical remission (median age 4.2 years) at the time of
      hematologic reconstitution after BFM-ALL induction therapy (treatment-free
      interval 22 days, median; range 12 to 52 days). All patients had experienced a
      period of leukopenia (white blood cell count [WBC] <0.95 x 10(9)/l, median)
      during the final four weeks of induction therapy. T-cells and T-cell subsets were
      examined by FACS. RESULTS: At the time of investigation the WBC was near normal
      (3.5 x 10(9)/l, median). Surprisingly, most cases (78%) showed a complete
      regeneration of T-cells and its subsets including 1) normal total (CD3+) T-cells
      (1635/microl, median; range 756-3440/microl); 2) normal T-helper (CD4+) cells
      (697/microl, median; range 128-1523/microl); and 3) normal T-cytotoxic/suppressor
      (CD8+) cells (686/microl, median; range 348-1540/microl). Eight patients achieved
      a normal CD4+/CD8+ ratio (0.8, median). Subset analyses of T-helper cells
      revealed a normal proportion of CD4+CD45RA+ cells (52%, median) in all but one
      patient below the age of 6 years, indicating an intact residual thymic activity.
      No correlation was observed between age at diagnosis and a normal CD4+ count (r =
      0.086) or between a normal CD4+ count and a normal proportion of CD4+CD45RA+
      cells r = 0.136). A long-term survey in four patients showed altered T-cells
      after reinduction and during maintenance therapy. CONCLUSIONS: The findings
      suggest that ALL per se does not inhibit T-cell regenerative capacity. Thus, the
      frequently observed longlasting impairment of the T-cell system in ALL is
      attributable to the treatment rather than to the underlying disease.

PMID- 11452937
TI  - Ewing sarcoma and sinonasal neuroectodermal tumors as second malignant tumors
      after retinoblastoma and other neoplasms.
AB  - BACKGROUND: Excesses of various childhood cancers have been reported after
      retinoblastoma, including a trickle of Ewing sarcoma (ES) and perhaps
      histologically similar olfactory neuroblastoma, both of which are neural tumors.
      To update and advance this information, case reports were sought by an extensive
      review of the literature. PROCEDURE: The search was made through the use of
      PubMed, and the Web of Science (Citation Index Expanded), keying on primary
      references. Three sinonasal cancers diagnosed as ES were immunohistochemically
      stained for MIC-2 protein (positive in ES). RESULTS: Retinoblastoma occurred
      before ES in ten cases (seven bilateral). In four others, retinoblastoma (three
      bilateral) developed before sinonasal neural tumors (poorly differentiated). ES
      also occurred after 14 cancers other than retinoblastoma (five lymphomas, four
      leukemias, and one each of five miscellaneous cancers). The predominance of
      retinoblastoma prior to ES differs markedly from the low-frequency of
      retinoblastoma among childhood cancers in the general population. On the
      contrary, cancers other than retinoblastoma were proportionate to those in the
      general population. Previously, retinoblastoma followed by excesses of
      osteosarcoma and soft tissue sarcomas has been attributed to the action of the
      inherited RB-1 gene. The sinonasal tumors stained negative for MIC-2 protein.
      CONCLUSIONS: Heritable retinoblastoma may predispose to ES and perhaps to a
      subset of poorly differentiated neuroectodermal tumors in the sinonasal region
      that may be related to olfactory neuroblastoma.

PMID- 11452938
TI  - Stature loss following treatment for Wilms tumor.
AB  - BACKGROUND: The study was designed to estimate reduction in adult stature induced
      by megavoltage radiation therapy (RT) of the spine in children treated for Wilms
      tumor and to ascertain whether the dose reduction in successive National Wilms
      Tumor Study Group (NWTSG) trials has mitigated late effects of RT in these
      children. PROCEDURE: Effects of RT dose, age at treatment, and chemotherapy on
      stature of 2,778 children with Wilms or another solid tumor of the kidney were
      analyzed using statistical models accounting for the dependence of height on
      gender and advancing age. Model predictions were validated by descriptive
      analysis of heights measured at 17 to 18 years of age for 205 patients. RESULTS:
      Radiation-induced reductions below normal height depended on dose, portal size,
      and age at treatment and were not augmented by doxorubicin or cyclophosphamide.
      Younger children were more strongly affected. Predicted height deficit at age 18
      years was 1.8 cm for a child treated with 10 Gy to the flank at age 4 years.
      Observed height deficits at age 1 7 to 18 years were 4.1 cm for 57 patients who
      received 15-24 Gy at a mean age of 55 months and zero for 16 children who
      received RT doses under 15 Gy at a mean age of 83 months. CONCLUSIONS: Reduction
      in stature following RT to the pediatric spine is dose- and age-dependent,
      persists into adulthood, and is not exacerbated by doxorubicin or
      cyclophosphamide. Average height deficits observed at maturity for children
      receiving doses currently recommended by the NWTSG are clinically nonsignificant.

PMID- 11452939
TI  - Pediatric oncology in developing countries: development of an alliance of
      stakeholders.

PMID- 11452940
TI  - Alliances in pediatric oncology: where do we go from here?

PMID- 11452941
TI  - International note: the walls of a spacious room.

PMID- 11452942
TI  - Langerhans cell histiocytosis in two generations: a new family and review of the
      literature.

PMID- 11452943
TI  - Extrarenal malignant rhabdoid tumors in childhood.

PMID- 11452944
TI  - Spontaneous remission of multifocal infantile hemangiopericytoma.

PMID- 11452945
TI  - Detection of choroid plexus carcinoma with Tc-99m sestamibi: case report and
      review of the literature.

PMID- 11452946
TI  - Epstein-Barr virus (EBV) induced hemophagocytic syndrome followed by EBV
      associated T/NK lymphoma in a child with perinatal human immunodeficiency virus
      (HIV) infection.

PMID- 11452947
TI  - Successful treatment of an Epstein-Barr virus-associated B-cell
      lymphoproliferative disease in a child with acute lymphoblastic leukemia using an
      anti-CD20 monoclonal antibody.

PMID- 11452948
TI  - Carboplatin and doxorubicin (CARDOX) for nonmetastatic hepatoblastoma: a
      discouraging pilot study.

PMID- 11452949
TI  - Ominous trend in childhood cancer mortality?

PMID- 11452950
TI  - Management and sequelae after misapplied intrathecal dactinomycin.

PMID- 11452951
TI  - Vertebral chloroma in a 1 1/2-year-old boy with no evidence of leukemia.

PMID- 11452952
TI  - Flavonol glycosides from leaves of Costus spiralis.
AB  - A new flavonol diglycoside, 3,5-dihydroxy-7,4'-dimethoxyflavone 3-O
      neohesperidoside (1), together with four known flavonol 3-O-neohesperidosides
      were isolated from the leaves of Costus spiralis and their structures were
      elucidated by a combination of spectroscopic methods and chemical reactions.

PMID- 11452953
TI  - Response to an infectious insult (e.g., bacterial or fungal infection).

PMID- 11452954
TI  - [Information- and communication technology in the public health sector].

PMID- 11452955
TI  - Rave on. Ecstasy use continues to grow & present new problems for EMS.

PMID- 11452956
TI  - Specialty distribution still in phone, fax age.

PMID- 11452957
TI  - [Summary of interdisciplinary Professional Society of Gynecological Oncology
      guidelines for diagnosis and therapy of cervix carcinoma].

PMID- 11452958
TI  - Ocular injures caused by intraocular or retrobulbar foreign bodies.

PMID- 11452959
TI  - Reply to Carole M. Lannon and the task force on circumcision.

PMID- 11452960
TI  - Sudden infant death syndrome and sleeping position.

PMID- 11452961
TI  - High-frequency oscillation and chronic lung disease in very low birth weight
      infants.

PMID- 11452963
TI  - E148Q of the MEFV gene causes amyloidosis in familial Mediterranean fever
      patients.

PMID- 11452964
TI  - Treatment of invasive Candida infection in neonates with congenital cutaneous
      Candidiasis.

PMID- 11452965
TI  - Age at operation for children with atrioventriculal canal.

PMID- 11452966
TI  - Folate and vitamin B12 supplementation in very low birth weight infants treated
      with erythropoietin: a cautionary note.

PMID- 11452967
TI  - Early adiposity rebound is not associated with energy or fat intake in infancy.

PMID- 11452968
TI  - The Rotavirus vaccine story.

PMID- 11452969
TI  - Vagal nerve stimulation in the epileptic encephalopathies: 3-year follow-up.

PMID- 11452970
TI  - STEP--a System for Teaching Experimental Psychology using E-Prime.
AB  - Students in psychology need to learn to design and analyze their own experiments.
      However, software that allows students to build experiments on their own has been
      limited in a variety of ways. The shipping of the first full release of the E
      Prime system later this year will open up a new opportunity for addressing this
      problem. Because E-Prime promises to become the standard for building experiments
      in psychology, it is now possible to construct a Web-based resource that uses E
      Prime as the delivery engine for a wide variety of instructional materials. This
      new system, funded by the National Science Foundation, is called STEP (System for
      the Teaching of Experimental Psychology). The goal of the STEP Project is to
      provide instructional materials that will facilitate the use of E-Prime in
      various learning contexts. We are now compiling a large set of classic
      experiments implemented in E-Prime and available over the Internet from
      http://step.psy.cmu.edu. The Web site also distributes instructional materials
      for building courses in experimental psychology based on E-Prime.

PMID- 11452971
TI  - Thigh mass in a 52-year-old woman.

PMID- 11452972
TI  - Moral issues of human embryo research.

PMID- 11452973
TI  - Stem cell research has only just begun.

PMID- 11452974
TI  - Stem cell research has only just begun.

PMID- 11452975
TI  - Prospects of a revived OTA for Congress.

PMID- 11452976
TI  - Increase competition to stabilize drug prices.

PMID- 11452977
TI  - National astronomical observatories in China.

PMID- 11452978
TI  - Asparagine uptake in rat hepatocytes: resolution of a paradox and insights into
      substrate-dependent transporter regulation.
AB  - Extracellular asparagine has previously been shown to markedly stimulate both
      ornithine decarboxylase and System N-mediated glutamine transport activities in
      hepatocytes by a transport-dependent mechanism. However, as a weak substrate of
      its inferred transporter System N, the specific route of asparagine uptake has
      remained enigmatic. In this study, asparagine transport was studied in detail and
      shown to be Na+-dependent, Li+-tolerant, stereospecific, and inhibited profoundly
      by glutamine and histidine. Coupled with competitive inhibition by glutamine (Ki
      = 2.63+/-1.11 mM), the data indicated that asparagine was indeed slowly
      transported by System N in rat hepatocytes, albeit at rates an order of magnitude
      less than for glutamine. The differential substrate transport velocities were
      shown to be attributable to a low transporter asparagine affinity (Km = 9.3 -
      17.5mM) compared to glutamine (Km approximately 1 mM). Consistent with its slow
      uptake, asparagine accumulated to a fivefold lesser degree than glutamine after
      60 min, yet stimulated System N activity to the same extent as glutamine. The
      transaminase inhibitor aminooxyacetate and starvation of the donor animal each
      enhanced asparagine uptake twofold and augmented subsequent transporter
      activation. Conversely, asparagine-dependent System N stimulation was abrogated
      by hyperosmotic media and blunted 30%-40% by phosphatidylinositol 3-kinase (PI3K)
      inhibitors wortmannin and LY294002. Collectively, the data suggest that System N
      mediated asparagine uptake serves an autostimulatory role, mediated by cellular
      swelling and in part by a PI3K-dependent signal transduction pathway.

PMID- 11452979
TI  - Pharmacological elevation of endogenous kynurenic acid levels activates nigral
      dopamine neurons.
AB  - Inhibitors of kynurenine 3-hydroxylase have previously been used to increase
      endogenous levels of kynurenic acid, an excitatory amino acid receptor
      antagonist. In the present electrophysiological study PNU 156561A was utilized to
      elevate endogenous concentrations of kynurenic acid and subsequent effects on the
      firing pattern of dopamine (DA) neurons of rat substantia nigra (SN) were
      analyzed. Pretreatment with PNU 156561A (40 mg/kg, i.v., 5-7 h) caused a five
      fold increase in endogenous kynurenic acid levels in whole brain five to seven
      hours after administration and also evoked a significant increase in firing rate
      and bursting activity of nigral DA neurons. The results of the present study show
      that a moderate increase in endogenous kynurenic acid levels produces significant
      actions on the tonic glutamatergic control of the firing pattern of nigral DA
      neurons, and implicate kynurenine 3-hydroxylase inhibitors as novel
      antiparkinsonian agents.

PMID- 11452980
TI  - The effect of heat shock on amino acid transport and cell volume in 3T3 cells.
AB  - In 3T3 cells temperatures higher than physiological stimulated amino acid
      transport activity in a dose-dependent manner up to 44 degrees C. However, the
      temperature increase did not induce widespread transport increase of all other
      nutrients tested. The activities of both amino acid transport systems A and ASC
      were enhanced within a few minutes following cell exposure to increased
      temperature. The maintenance of this effect required continuous exposure of the
      cells to hyperthermia. Kinetic analysis indicated that the stimulation of the
      activity of transport System A occurred through a mechanism affecting Vmax rather
      than Km. The continuous presence of cycloheximide did not prevent the transport
      changes induced by hyperthermia. These results suggest that the increased amino
      acid uptake reflects an activation or relocation of existing amino acid transport
      proteins. During the hyperthermic treatment, the content of ninhydrin-positive
      substances (NPS), mostly amino acids, increased within the cells and the
      accumulation of these compatible osmolytes was parallelled by an increase in cell
      volume. The withdrawal of amino acids from the culture medium immediately before
      and during the shock phase counteracted the increase and reduced the NPS content
      but did not prevent the increase in amino acid transport, the cell swelling and
      the induction of the heat shock response.

PMID- 11452981
TI  - New quinone-amino acid conjugates linked via a vinylic spacer.
AB  - Chloranil and 2,3-dichloro-1,4-naphthoquinone have been linked to different
      natural and unnatural amino acids via a vinylic spacer. Two routes were developed
      for the facile preparation of these novel modified amino acids: the direct
      method, which can only be applied to secondary amines, and the indirect method
      (transamination reaction), which can be applied to any amino acid or ester.

PMID- 11452982
TI  - Impact of separating amino acids between plasma, extracellular and intracellular
      compartments on estimating protein synthesis in rodents.
AB  - Three models representing different separations of amino acid sources were used
      to simulate experimental specific radioactivity data and to predict protein
      fractional synthesis rate (FSR). Data were from a pulse dose of 14C-U Leu given
      to a non-growing 20-g mouse and a flooding dose of 3H Phe given to a non-growing
      200 g rat. Protein synthesis rates estimated using the combined extracellular and
      intracellular (Ec + Ic) source pool and extracellular and plasma (Ec + Pls)
      source pool mouse models were 78 and 120% d(-1) in liver, 14 and 16% d(-1) in
      brain and 15 and 14% d(-1) in muscle. Predicted protein synthesis rates using the
      Ec + Ic, Ec + Ic + Tr (combined extracellular, intracellular and aminoacyl tRNA
      source pool) and Ec + Pls rat models were 57, 3.4 and 57% d(-1) in gastrocnemius,
      58, 71 and 62% d(-1) in gut, 8.3, 8.4 and 7.9% d(-1) in heart, 32, 23 and 25% d(
      1) in kidney, 160, 90 and 80% d(-1) in liver, 57, 5.5 and 57% d(-1) in soleus and
      56, 3.4 and 57% d(-1) in tibialis. The Ec + Ic + Tr model underestimated protein
      synthesis rates in mouse tissues (5.0, 27 and 2.5% d(-1) for brain, liver and
      muscle) and rat muscles (3.4, 5.5 and 3.4% d(-1) for gastrocnemius, soleus and
      tibialis). The Ec + Pls model predicted the mouse pulse dose data best and the Ec
      + Ic model predicted the rat flooding dose data best. Model predictions of FSR
      imply that identification and separation of the source specific radioactivity is
      critical to accurately estimate FSR.

PMID- 11452983
TI  - Assignment of D-amino-acid oxidase gene to a human and a mouse chromosome.
AB  - A part of D-amino-acid oxidase gene was amplified in the human and mouse by
      polymerase chain reaction. The amplified fragments were ligated to plasmids and
      then cloned. The plasmids containing the parts of D-amino-acid oxidase gene were
      biotinylated and hybridized to human and mouse metaphase chromosomes. The
      chromosomal slides were treated with fluorescein isothiocyanate (FITC)-conjugated
      avidin. The hybridized signals were amplified with biotinylated anti-avidin
      antibody and FITC-avidin. The chromosomes were counter-stained with diamidino
      phenylindole for assignment of the signal to a specific band. Using this
      fluorescence in situ hybridization (FISH), D-amino-acid oxidase gene was assigned
      to human chromosome 12q23-24.1 and mouse chromosome 5E3-F. Since these regions
      are syntenic between human and mouse, the present results indicate that the locus
      for this enzyme has been conserved through evolution.

PMID- 11452984
TI  - Homocysteine concentrations in a German cohort of 500 individuals: reference
      ranges and determinants of plasma levels in healthy children and their parents.
AB  - Elevated plasma homocysteine is a risk factor for cardiovascular disease and a
      sensitive marker of inadequate vitamin B12 and folate status. We studied 257
      pupils (120 boys, 137 girls, aged 6-17 years) and their parents (88 males, 172
      females, aged 26-50 years). Our measurements were part of a national Bavarian
      health and nutrition examination survey evaluating cardiovascular risk factors. A
      mild hyperhomocysteinemia (Hcys >15 micromol/l) occurred in 7% of the adults, but
      in none of the children. Men had significantly higher Hcys levels than women
      (p<0.0001), boys and girls had comparable concentrations. For adults and
      children, Hcys correlated inversely with vitamin B12 and folate and positively
      with the lean body mass and creatinine in serum, but not with cystatin C. Genetic
      and nutritional factors are determinants of Hcys metabolism. The correlation of
      Hcys and serum creatinine is dependent on the metabolic link between Hcys
      production and creatine synthesis.

PMID- 11452985
TI  - Taurine is a weak scavenger of peroxynitrite and does not attenuate sodium
      nitroprusside toxicity to cells in culture.
AB  - Many studies have suggested an antioxidant role for taurine, but few studies have
      directly measured its free radical scavenging activity. The aim of the present
      study was to directly determine the action of taurine and taurine analogs to
      inhibit peroxynitrite-mediated oxidation of dihydrorhodamine 123 (DHR) to
      rhodamine. Taurine was also tested to determine if it could attenuate the
      toxicity of sodium nitroprusside (SNP) to neuronal cultures. Taurine at
      concentrations above 30 mM had a modest ability to inhibit peroxynitrite
      formation derived from SIN-1. Hypotaurine could inhibit peroxynitrite formation
      from both SIN-1 (decrease 75%) and SNP (decrease 50%) at 10 mM. Other taurine
      analogs (homotaurine, beta-alanine & isethionic acid) slightly potentiated DHR
      oxidation by SIN-1. Short-term (1-hour) treatment of PC12 cultures with either
      SNP (1-2mM) or taurine (20-40 mM) appeared to induce cellular proliferation. In
      contrast, 24-hour treatment with SNP (1 mM) induced cell death. Combination
      treatments with taurine and SNP appeared to interact in an additive fashion for
      both cell proliferation and neurotoxic actions. It appears unlikely that taurine
      is a major endogenous scavenger of peroxynitrite.

PMID- 11452986
TI  - Detection of moderate hyperhomocysteinemia: comparison of the Abbott fluorescence
      polarization immunoassay with the Bio-Rad and SBD-F high-performance liquid
      chromatographic assays.
AB  - The importance of accurate methods for homocysteine measurement has been
      emphasized. We compared the results obtained with the most commonly used high
      performance liquid chromatography (HPLC) assay, and two recently commercially
      available methods: another HPLC and a fluorescence polarization immunoassay, in
      plasmas from normo- or hyperhomocysteinemic patients. A significant agreement
      between the different methods in classifying the results as hyper or normal
      homocysteinemia was observed. However, a significant difference between the
      results was found. Standardization is urgently necessary to improve the
      concordance of homocysteine determination.

PMID- 11452987
TI  - Retention behavior of transition metals on a bifunctional ion-exchange column
      with oxalic acid as eluent.
AB  - The common eluents used with a bifunctional ion-exchange column (IonPac CS5A) for
      separating transition metals are pyridine-2,6-dicarboxylic acid and oxalic acid
      (Ox). When Ox is used, cadmium and manganese co-elute. Although much research has
      been done to overcome the Cd2+-Mn2+ co-elution problem, the role of lithium
      hydroxide in separating the transition metals has received little attention. In
      this study, it is found that when the Ox concentration is higher than 35 mM, Cu2+
      elutes after Pb2+ and Ox plays a predominant role in the retention behavior of
      the seven metals. When Ox concentration is lower than 35 mM especially when its
      concentration (25 mM) is half of the usually used standard concentration (50 mM),
      Cu2+ elutes before Pb2+, and at the same time, Mn2+ and Cd2+ can also be baseline
      separated. Lithium hydroxide plays a predominant role in the separation of the
      metals separated by cation exchange. So, lithium hydroxide is used to adjust the
      pH of the eluent. The use of an isocratic elution (25 mM Ox/LiOH/2 mM Na2SO4, pH
      3.88) allows the separation of seven metals (Cu2+, Pb2+, Co2+, Mn2+, Cd2+, Zn2+
      and Ni2+) in a single run. The effects of inorganic modifiers such as NaNO3,
      Na2SO4 and Na4P3O7 on retention behavior of the metals are also investigated.

PMID- 11452988
TI  - Simultaneous separation of common mono- and divalent cations on a zirconium
      modified silica gel column by ion chromatography with non-suppressed
      conductimetric detection and tartaric acid-15-crown-5 as eluent.
AB  - The application of laboratory-made zirconium-modified silica gels (Zr-silicas) as
      cation-exchange stationary phases to ion chromatography with conductimetric
      detection (IC-CD) for common mono- and divalent cations (Li+, Na+, NH4+, K+, Mg2+
      and Ca2+) was carried out. Zr-silicas were prepared by the reaction of the
      silanol group on the surface of silica gel with zirconium tetrabutoxide
      (Zr(OCH2CH2CH2CH3)4) in ethanol. Zr-silica adsorbed on 10 mg zirconium g(-1)
      silica gel was a suitable cation-exchange stationary phase in IC-CD for the
      separation of these mono- and divalent cations. Excellent simultaneous separation
      and highly sensitive detection for these cations were achieved in 10 min by IC-CD
      using a Zr-silica column (150x4.6 mm I.D.) and 10 mM tartaric acid containing 10
      mM 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane) as the eluent. The proposed
      IC-CD method was successfully applied to the determination of major mono- and
      divalent cations in natural water samples.

PMID- 11452989
TI  - Effect of organic solvents in the on-line thermal lens spectrometric detection of
      chromium(III) and chromium(VI) after ion chromatographic separation.
AB  - The effect of methanol, acetone and acetonitrile on the sensitivity, selectivity
      and the detection limits (LODs) of the determination of chromium species by ion
      chromatography was investigated. A collinear dual-beam thermal lens spectrometer
      was used for the direct detection of chromium complexes [pre-column derivatized
      Cr(III)-pyridine-2,6-dicarboxylic acid, and post-column derivatized Cr(VI)-1,5
      diphenylcarbazide] following the ion chromatographic separation on a Dionex HPIC
      CS5A solvent compatible column. Different amounts of organic solvents were added
      directly to the eluent (up to 30%) and to the post-column reagent (up to 60%) to
      improve the thermooptical properties of the solvents. Consequently, the
      sensitivity of the technique was increased by a factor of 2-3 and LODs of 0.1 and
      10 microg dm(-3) were achieved for Cr(VI) and Cr(III), respectively, when the
      eluent reaching the detector contained 30% of acetonitrile. The addition of
      organic solvents also resulted in significant changes in retention times, which
      improved the Cr(III)/Cr(VI) separation.

PMID- 11452990
TI  - Determination of trace anions in high-nitrate matrices by ion chromatography.
AB  - An ion chromatography method was developed to determine trace anionic
      contamination in matrices that have a high concentration of nitrate ion.
      Contaminant anions of interest were separated on an IonPac AS15 high-capacity
      anion-exchange column and detected by suppressed conductivity detection. An EG40
      eluent generator was used to prepare high-purity and carbonate-free potassium
      hydroxide. Using the EG40, performance at trace levels was enhanced because
      background conductivity decreased and retention time reproducibility improved.
      Trace anionic contamination from the mobile phase was minimized when using the
      eluent generator compared to using conventionally prepared sodium hydroxide
      eluents. The signal-to-noise ratio was also improved with the use of a
      temperature controlled conductivity cell and chromatography hardware in the
      microbore (2-mm) format. The eluent concentration was optimized to separate the
      contaminant anions from the excess of the nitrate matrix ions. The procedure was
      demonstrated for a solution of reagent-grade sodium nitrate and high-purity 0.7%
      nitric acid. Method detection limits for chloride, sulfate and phosphate of 150
      microg/l and lower were achieved.

PMID- 11452991
TI  - Sub-ambient temperature effects on the separation of monosaccharides by high
      performance anion-exchange chromatography with pulse amperometric detection.
      Application to marine chemistry.
AB  - The effects of column temperature in the range 10-45 degrees C using high
      performance anion-exchange chromatography (HPAEC) and pulse amperometric
      detection are described for the determination of monosaccharides. The influence
      of temperature was tested with an isocratic elution of NaOH at concentrations
      varying from 2.5 to 20 mM and with a post-column addition of 1 M NaOH. The
      results showed that small changes of temperature greatly affect retention times
      and resolution (Rs) of monosaccharides and particularly those of the both pairs
      xylose-mannose and rhamnose-arabinose which cannot be simultaneously detected at
      usual room temperature (approximately 25 degrees C). Our results suggest that a
      subambient temperature of 17 degrees C and an eluent concentration of 19 mM are
      the more appropriate conditions for an acceptable separation (R(s rha/ara) =
      1.02, R(s man/xyl) = 0.70) in a short analytical run time (35 min). The results
      showed that within the range of temperatures studied, enthalpy and entropy are
      invariant of temperature indicating that changes in the retention processes are
      mainly due to temperature than other associated changes in the system. This study
      demonstrated the importance of controlling temperature during HPAEC of
      monosaccharides, both to accomplish highly reproducible retention times and to
      achieve optimal separation of sugars. This method gave acceptable results for
      detection of marine sugars.

PMID- 11452992
TI  - Chemiluminescence nitrogen detection in ion chromatography for the determination
      of nitrogen-containing anions.
AB  - Chemiluminescence nitrogen detection (CLND) provides equimolar response for
      nitrogen-containing ions such as nitrate, nitrite, cyanide, ammonium and
      tetradecyltrimethylammonium. Only azide yields a lower response. Nitrite, azide
      and nitrate are separated on a Dionex AS11 column using 5 nM NaOH as eluent with
      a 3 microM (1 ng N) limit of detection. Matrices, such as 1:10 diluted seawater,
      do not degrade these detection limits. CLND also provides equally sensitive
      (limit of detection 3 microM, 78 ppb) detection of weak acids such, as cyanide,
      which yield poor sensitivity with suppressed conductivity detection.

PMID- 11452993
TI  - Ion-chromatographic analysis of common anions, acetate, and formate in 30%
      hydrogen peroxide statistical evaluation of two automated microbore systems.
AB  - Two hydroxide-selective microbore analytical columns (the Dionex AS11 and AS15)
      were tested and compared for the quantitation of anionic species in 30% hydrogen
      peroxide. The ions of interest were fluoride, acetate, formate, chloride,
      bromide, nitrate, sulfate, and phosphate. Statistically sound calibration and
      spiking studies were carried out, investigating the range of a blank to 60 ppb.
      Prior to injection onto the separators, peroxides were loaded without
      pretreatment onto a concentrator column, which was then washed with deionized
      water to remove the matrix. Although retention times gradually decreased during
      the spiking studies, reliable quantitation was still achievable on both columns
      at the target concentration of 30 ppb. However, various resolution problems meant
      that the AS11 should not be recommended for this application.

PMID- 11452994
TI  - Analysis of residual trifluoroacetic acid in a phosphate-buffered saline matrix
      by ion chromatography with suppressed conductivity detection.
AB  - As part of the formulation of a cell-based pharmaceutical product, cells were
      harvested from mice and incubated in a cocktail containing cell culture media and
      high levels of trifluoroacetic acid (TFA). The cells were washed with a phosphate
      buffered saline solution to remove residual cell culture media and other reagents
      before the cells were infused back into the mice from which they originated.
      Because of the potentially toxic nature of the TFA, the cells were washed
      multiple times and the final wash was monitored for residual TFA in order to
      demonstrate the efficient removal of the reagent before the cell product could be
      reintroduced into the test animal. This report describes the method that was
      developed incorporating anion-exchange chromatography with suppressed
      conductivity detection for the analysis of residual TFA (down to 50 ng/ml) in the
      presence of high concentrations of phosphate and chloride interferences. The
      ultimate sensitivity of the method was improved by selectively removing halide
      anions using a silver cartridge before sample analysis. The method proved to be
      rugged and reproducible enough to be validated and used to monitor residual TFA
      levels in cell washes in support of an acute toxicological study. Results
      demonstrating the method's sensitivity, selectivity, precision and linearity were
      reported.

PMID- 11452995
TI  - Ion-pair chromatography of polythionates and thiosulfate with detection based on
      their catalytic effects on the postcolumn azide-iodine reaction.
AB  - The reduction of iodine with azide, catalyzed by polythionates (tri-, tetra-,
      penta- and hexathionate) and thiosulfate, has been utilized as a postcolumn
      reaction for chromatographic determination of these sulfur oxyanions. The method
      is based on the separation of polythionates and thiosulfate on an octadecylsilica
      column with an acetonitrile-water (20:80, v/v) mobile phase (pH 5.0) containing 3
      mM tetrapropylammonium hydroxide and 6 mM acetic acid, followed by photometric
      measurement of the residual iodine (as triiodide) from the catalytic postcolumn
      azide-iodine reaction after mixing a reaction solution containing azide and
      iodine with the column effluent. Chromatograms obtained for the sulfur oxyanions
      showed negative peaks as a result of the decrease in absorbance of background.
      The conditions for the catalytic postcolumn reaction of the sulfur oxyanions in
      the column effluents were established by varying the concentrations of azide,
      iodine, iodide and acetic acid in the reaction solution, and varying the flow
      rate, reaction temperature and length of the reaction tube. The detection limits
      (defined as SIN = 3) were 4.3 microM for trithionate, 0.10 microM for
      tetrathionate, 2.7 nM for pentathionate, 5.0 nM for hexathionate and 1.1 nM for
      thiosulfate. When compared with earlier methods, the proposed method gave a much
      higher sensitivity for the determination of two polythionates (penta- and
      hexathionate) and thiosulfate. This method was applied successfully to the
      analysis of polythionates and thiosulfate added to hot-spring water samples.

PMID- 11452996
TI  - Separation of perfluoroalkylsulfinic acids and perfluoroalkylsulfonic acids by
      ion-exclusion chromatography.
AB  - Ion-exclusion chromatography has been successfully applied to the separation of a
      number of perfluoroalkylsulfinic acids and perfluoroalkylsulfonic acids. The
      separation of various perfluoroalkylsulfinic and perfluoroalkylsulfonic acids,
      with different alkyl groups, was investigated on a polymethacrylate-based, weakly
      acidic, cation-exchange resin (TSK gel OApak-A) in the H+-form and using
      conductimetric detection. When water was used as the eluent, these
      perfluoroalkylsulfinic and perfluoroalkylsulfonic acids could not be resolved.
      When an aqueous solution of benzoic acid and o-phthalic acid was used, the
      separation of each of these acids occurred. In order to improve their separation,
      the effect of the addition of methanol and 2,2,2-trifluoroethanol, as organic
      modifiers, was also investigated.

PMID- 11452997
TI  - Application of zirconium-modified silica gel as a stationary phase in the ion
      exclusion chromatography of carboxylic acids. II. Separation of aliphatic
      carboxylic acids with pyromellitic acid as eluent and with suppressed
      conductimetric detection.
AB  - The application of zirconium-modified silica gels (Zr-Silica) as stationary
      phases for ion-exclusion chromatography with conductimetric detection (IEC-CD)
      for C1-C8 aliphatic carboxylic acids (formic, acetic, propionic, butyric,
      valeric, caproic, heptanoic and caprylic acids) was carried out using
      pyromellitic acid as the eluent. Zr-Silicas were prepared by the reaction of the
      silanol group on the surface of silica gel with zirconium tetrabutoxide
      [Zr(OCH2CH2CH2CH3)4] in ethanol solution. An ASRS-Ultra anion self-regenerating
      suppressor in the K+ form was used for the enhancement of conductimetric detector
      response of these aliphatic carboxylic acids. A Zr-Silica adsorbed on 10 mg
      zirconium g(-1) silica gel was the most suitable stationary phase in IEC-CD for
      the separation of these aliphatic carboxylic acids. Excellent simultaneous
      separation and highly sensitive detection for these aliphatic carboxylic acids
      were achieved in 25 min by IEC-CD with the Zr-Silica column (250x4.6 mm I.D.) and
      a 0.2 mM pyromellitic acid containing 0.15% heptanol as the eluent.

PMID- 11452998
TI  - Continuous melting and ion chromatographic analyses of ice cores.
AB  - A new method for determining concentrations of organic and inorganic ions in ice
      cores by continuous melting and contemporaneous ion chromatographic analyses was
      developed. A subcore is melted on a melting device and the meltwater produced is
      collected in two parallel sample loops and then analyzed simultaneously by two
      ion chromatographs, one for anions and one for cations. For most of the analyzed
      species, lower or equal blank values were achieved with the continuous melting
      and analysis technique compared to the conventional analysis. Comparison of the
      continuous melting and ion chromatographic analysis with the conventional
      analysis of a real ice core segment showed good agreement in concentration
      profiles and total amounts of ionic species. Thus, the newly developed method is
      well suited for ice core analysis and has the advantages of lower ice
      consumption, less time-consuming sample preparation and lower risk of
      contamination.

PMID- 11452999
TI  - Ion chromatographic determination of lithium at trace level concentrations.
      Application to a tracer experiment in a high-mountain lake.
AB  - The water residence time of a high-mountain seepage lake in the Austrian Alps was
      derived from the flushing rate of a tracer substance. A diluted lithium chloride
      solution was injected into the lake during holomictic conditions in order to
      favour the homogeneous distribution of the tracer. The exponential decline of the
      mass of lithium in the lake revealed a water residence time of 1.5 to 3 months
      for summer and almost no lake water exchange during winter. Lithium
      concentrations ranged from background values of 0.06 microg l(-1) to about 3
      microg l(-1) immediately after the tracer injection. Lake water samples were
      analyzed with ion-exchange chromatography using a Dionex device with a CS 12A
      separation column. The method detection limit determined according to the
      definition of the US Envirinmental Protection Agency amounted to 0.009 microg l(
      1).

PMID- 11453000
TI  - Comparison of three post-column reaction methods for the analysis of bromate and
      nitrite in drinking water.
AB  - Three post-column ion chromatographic methods (i.e., a sodium bromide-sodium
      nitrite method, an o-dianisidine method, and a potassium iodide-ammonium
      heptamolybdate method) were compared for bromate and nitrite analysis. Also, the
      effect of direct mixing of the reagents without ion suppressors for the sodium
      bromide-sodium nitrite method and the potassium iodide-ammonium heptamolybdate
      method was investigated. For the analysis of bromate, the three methods showed
      similar method detection limits (0.17-0.24 microg/l) with pneumatic reagent
      delivery systems. Direct reagent mixing achieved comparable detection limits to
      the suppressor configuration. The three methods are also compatible with
      conductivity detection. When used in combination with conductivity detection,
      this compatibility allows simultaneous analysis of bromate, nitrite, and other
      common ions in drinking water, such as bromide. It was found that the o
      dianisidine method achieves microg/l-level detection of nitrite and bromate with
      a simpler configuration than the potassium iodide-ammonium heptamolybdate method,
      while the sodium bromide-sodium nitrite method was not sufficiently sensitive for
      nitrite analysis at the microg/l level.

PMID- 11453001
TI  - Use of ion chromatography with post-column reaction for the measurement of
      tribromide to evaluate bromate levels in drinking water.
AB  - A user-friendly ion chromatography method in conjunction with a post-column
      reaction (PCR) achieves practical quantitation limits for the oxyhalides bromate
      and chlorite of 0.05 microg/l and 0.10 microg/l, respectively. This level of
      measurement allows for the accurate assessment of bromate contributed to finished
      drinking waters that have been chlorinated using sodium hypochlorite. The target
      sensitivity of oxyhalides in the presence of other major ion species typically
      found in drinking water is achieved by PCR using excess bromide under acidic
      conditions to form a tribromide species that is detected by ultraviolet
      spectrometry. The method setup involves non-hazardous materials, as opposed to
      other recently developed methods that employ somewhat hazardous chemicals for
      generating the reaction necessary for the detection of bromate at sub-microg/l
      levels. No pretreatment of the samples is required, other than filtration and
      quenching of oxidant residual.

PMID- 11453002
TI  - Review of the methods of the US Environmental Protection Agency for bromate
      determination and validation of method 317.0 for disinfection by-product anions
      and low-level bromate.
AB  - In recent years several methods have been published by the United States
      Environmental Protection Agency (EPA) which specify bromate as a target analyte.
      The first of these was EPA Method 300.0. As technological improvements in ion
      chromatographic hardware have evolved and new detection techniques have been
      designed, method detection limits for bromate have been reduced and additional
      procedures have been written, including EPA Method 300.1, 321.8 and, most
      recently, EPA Method 317.0. An overview of the evolution of these bromate methods
      since 1989 is presented. The focus is specific to each of these respective
      procedures, highlighting method strengths, weaknesses, and addressing how these
      methods fit into EPA's regulatory agenda. In addition, performance data are
      presented detailing the joint EPA/American Society for Testing and Materials
      multilaboratory validation of EPA Method 317.0 for disinfection by-product anions
      and low-level bromate.

PMID- 11453003
TI  - Histidine as a dipolar eluent component in cation chromatography. II. Prediction
      of retention data for alkaline and alkaline-earth ions.
AB  - The utility of cation chromatography has been developed by the application of L
      histidine as a multiprotic and dipolar (zwitterionic) eluent component. The
      method simplifies the cation analysis. The chromatographic characteristics of
      this system were studied in detail with a view to determining the selectivity and
      the mechanism by which the cations (Na+, K+, Mg2+, Ca2+) are retained. Complete
      separations were observed in the isocratic run over the eluent concentration
      range 3.0-6.0 mM at pH below 2.0. Sensitive detection was achieved using
      suppressed conductivity at the pH of isoelectric point of the histidine.
      Retention equations are derived for mono- and divalent cations eluted from ion
      exchange separation column with multiple ionic eluents. The theory is based on
      the extension of ion-exchange equilibrium by protonation equilibria. The
      selectivity data for analyte and eluent species are deterrmined using the model
      from the experimental retention data by computer-assisted iterative calculations.
      The model was utilized to predict retention data. The results in three
      dimensional retention surfaces together with species distribution graphs are
      presented.

PMID- 11453004
TI  - Ion-chromatographic screening method for monitoring arsenate and other anionic
      pollutants in ground waters of Northern Italy.
AB  - A novel, rapid ion-chromatographic method for screening anionic pollutants in
      ground water, based on both conductivity and postcolumn spectrophotometric
      detection, has been developed. A relatively rapid separation of more than ten
      inorganic and polarizable anions was achieved by coupling an high capacity,
      hydroxide selective anion-exchange columns (Dionex IonPac AS16) supplied with an
      electrolytic eluent generator operating in gradient mode. The good control of the
      selectivity allowed the determination of polarizable anions including arsenate,
      thiocyanate, thiosulfate and perchlorate without interference from major
      components present at levels greater than 100 mg l(-1). This method was applied
      to the determination of arsenate in ground water samples collected in industrial
      and agricultural zones of Lombardia (Northern Italy). No traces of arsenate were
      detected in any sample, but added arsenate cannot be revealed by chromatographic
      analyses. This fact can be attributed to different causes, from reduction to the
      more reduced arsenic form to precipitation or dissolution in organic or inorganic
      based colloids. Oxidation with hydrogen peroxide seems to be useful for a partial
      recovery of added arsenate, but a stronger oxidation method, compatible with
      chromatographic separation, must be studied.

PMID- 11453005
TI  - High-performance ion-exclusion/cation-exchange chromatography of anions and
      cations in acid rain waters on a weakly acidic cation-exchange resin.
AB  - A new method for the simultaneous determination of anions (sulfate, nitrate, and
      chloride) and cations (sodium, ammonium, potassium, magnesium, and calcium) in
      acid rain waters was investigated using high-performance ion-exclusion/cation
      exchange chromatography with conductimetric detection on a separation column
      packed with a polymethacrylate-based weakly acidic cation-exchange resin in the
      hydrogen-form and an eluent comprising 1.5 mM sulfosalicylic acid-6 mM 18-crown-6
      at pH 2.6, operated at 1.5 ml/min. Effective separation and highly sensitive
      conductimetric detection for the anions and the cations was achieved in about 14
      min. Since the ionic balance (equivalents of anions/equivalents of cations) of
      acid rain waters of different pH (4.40-4.67) ranged from 0.97 to 0.94, evaluation
      of the water quality of acid rain was possible. This method was successfully
      applied to the simultaneous determination of the anions and the cations in acid
      rain transported from mainland China and North Korea to central Japan monitored
      by a meteorological satellite data analyzer.

PMID- 11453006
TI  - Analysis of fountain solutions for anionic components, including
      alkylbenzenesulfonates, carboxylates and polyphosphates, by a combination of ion
      exchange and ion-exclusion chromatography and inductively coupled plasma atomic
      emission spectrometry.
AB  - A method for the quantitative determination of the major anionic constituents of
      fountain solutions, typically mono-, di- and hydroxycarboxylates,
      alkylbenzenesulfonates, and inorganic anions, including orthophosphate and
      polyphosphates, is presented here for the first time. The analytical problems
      arising from extensive co-elution of many of these analytes on an ion-exchange
      column have been resolved through a combination of (i) careful selection of the
      concentration gradient of the sodium hydroxide eluent; (ii) parallel analysis by
      ion-exclusion chromatography; and (iii) determination of total phosphorus by
      inductively coupled plasma atomic emission spectrometry.

PMID- 11453007
TI  - Simple ion chromatographic method for the determination of chlormequat residues
      in pears.
AB  - Current methods for quantitative determination of chlormequat residues in food
      crops are characterized by rather low recoveries and the need for derivatization
      (in case of gas chromatography, GC), or by high capital investment (in case of
      liquid chromatography-mass spectrometry, LC-MS). We propose a cation-exchange
      chromatography method for the analysis of chlormequat in pears. The method is
      based on extraction of the target compound with 40 mM HCl, followed by
      centrifugation and filtration. The filtrate is directly injected into an ion
      chromatograph equipped with a commercially available cation-exchange column and a
      suppressed conductivity detection system. While the limit of detection (LOD) (0.5
      mg/kg) may not be small enough to allow dietary analysis, the method meets all
      validation requirements and is an alternative for the existing GC and LC-MS
      methods in quality control.

PMID- 11453008
TI  - Monitoring and statistical evaluation of heavy metals in airborne particulates in
      Cairo, Egypt.
AB  - Airborne particulate material was monitored as total suspended particles and
      particulate matter less than 10 microm at selected sites in Cairo. The selected
      sites represent heavily industrial and industrial-residential areas of Cairo,
      Egypt. The filters were further analyzed for lead, cadmium, zinc and nickel using
      ion chromatography. The chosen method was modified to improve resolution and
      decrease the retention time. The data obtained were treated statistically using
      one-way analysis of variance and correlated with the anthropological and
      industrial activities of the sites. The concentrations of the heavy metals are
      studied in terms of particle size, time dependence, and safety.

PMID- 11453009
TI  - Ammonium extraction method for ion chromatographic measurements of disc drive
      components.
AB  - The analysis of ionic micro-contamination is of growing importance in the disc
      drive industry. Through the use of ion chromatography, cleanliness of drive
      components can be assessed. An objective to improve quantification of highly
      reactive inorganic ions that exist within the drive environment was implemented.
      This paper presents a new extraction technique used to determine low levels of
      ammonium, by microbore ion chromatography. Various chemical compounds within
      adhesive formulations can be a source of extractable ammonium. By combining this
      new extraction method with ion chromatography, the percentage of different
      chemical compounds within adhesive formulations was correlated to the level of
      extractable ammonium observed.

PMID- 11453010
TI  - Improved determination of tributyl phosphate degradation products (mono- and
      dibutyl phosphates) by ion chromatography.
AB  - Tributyl phosphate (TBP) is a very important compound in the nuclear industry,
      particularly in the area of nuclear fuel reprocessing. This compound is used in
      the PUREX (plutonium and uranium refining extraction) process which consists of
      the extraction of uranium and plutonium from an aqueous nitric acid phase, for
      the purpose of recycling. But TBP may be degraded to dibutyl phosphate (DBP) and
      monobutyl phosphate (MBP) by dealkylation of one or two butoxy groups,
      respectively. We have compared and evaluated the capacity of two resins
      manufactured by Dionex (AS11 and AS5A) in the separation and measurement of these
      two degradation products. AS11 generates two interferences: nitrite/DBP and
      carbonate/MBP. The first one is the most serious. So, we have developed a method
      for oxidising nitrite ions to nitrate ions which have no trouble over the
      measurement. The second resin tested, AS5A, allows a very efficient separation
      between DBP and NO2- ions and a good separation between MBP and CO3(2-) in
      comparison with the AS11. The detection limits for the AS5A column are 0.13
      microM for MBP and 0.71 microM for DBP (injection loop=50 microl).

PMID- 11453011
TI  - Liquid chromatographic methods for chloral hydrate determination.
AB  - Liquid chromatographic methods, based on reversed-phase (RP) and anion-exchange
      mechanisms, have been developed for chloral hydrate determination. Both methods
      are preceeded by derivatization of chloral hydrate. For RP separations, different
      reagents [namely dansylhydrazine and o-(4-nitrobenzyl)hydroxylamine] have been
      studied, but the best results have been achieved using 1,2-benzenedithiol with UV
      detection at 220 nm. The anion-exchange method is based on derivatization with
      NaOH to form sodium formate that is then analyzed by anion-exchange, with
      suppressed conductivity detection. Derivatization conditions were optimized in
      order to reach the best yield of reaction. The optimization of the procedure
      allowed to determine chloral hydrate with detection limits as low as 0.2 microg/l
      with good linearity and reproducibility. The anion-exchange method was also
      applied for chloral hydrate determination in a drinking water sample. A
      preconcentration procedure has also been studied.

PMID- 11453012
TI  - Evaluation of fructans in various fresh and stewed fruits by high-performance
      anion-exchange chromatography with pulsed amperometric detection.
AB  - Fructans are food-grade non-digestible carbohydrates that exert beneficial
      nutritional effects. Their characterization and quantification is required for
      food-labeling purposes. We describe the suitability of high-performance anion
      exchange chromatography coupled with pulsed amperometric detection for the
      identification and quantification of fructans in fresh fruits (various apple and
      pear cultivars, plum, banana) as well as in commercial stewed fruits obtained
      from a local manufacturer. After extraction with water and appropriate
      filtration, inulobiose [beta-D-Fru-(2-->1)-beta-D-fructofuranoside; F2], 1
      kestose [beta-D-Fru-(2-->1)2-alpha-D-glucopyranoside; GF2] and nystose [beta-D
      Fru-(2-->1)3-alpha-D-glucopyranoside; GF3] were completely separated in a single
      36-min run using a Dionex CarboPac PA 100 column and the new quadruple-potential
      waveform, originally tailored for oligosaccharide separation. No measurable
      amounts of F3 and GF4 were detected within the group of studied fruit products.
      Peak identification was realized using standards. The method is easy,
      reproducible, and sensitive since as little as 28 microg of sugar per gram dry
      matter can be quantified. Banana and plum are the varieties containing the
      highest levels of fructans (about 6000 microg per gram dry matter). The maturity
      of the fruit appears to have a great influence on the level of GF2. Samples of
      apple-banana stewed fruits contained the highest total fructan concentration
      (about 700 microg per gram dry matter). Accurate quantification of fructans will
      allow more precise nutritional formulation and diet selection for higher fructan
      consumption.

PMID- 11453013
TI  - Separation and identification of enzymatic sucrose hydrolysis products by high
      performance anion-exchange chromatography with pulsed amperometric detection.
AB  - An accurate carbohydrate analysis method, namely high-performance anion-exchange
      chromatography with pulsed amperometric detection was successfully applied to the
      study of sucrose hydrolysis under enzymatic (baker's yeast invertase) conditions.
      The hydrolysis was monitored by determining sucrose degradation and the
      corresponding formation of D-glucose, D-fructose and five intermediate fructans
      using a CarboPac PA-100 (Dionex) analytical anion-exchange column. Highly
      reproducible results were obtained. The unknown fructans were collected from a
      semi-preparative CarboPac PA-100 (Dionex) column, neutralized and then desalted
      on a column containing mixed bed resin AG 501-X8 (D) before identification of the
      chemical structure. This procedure permitted us to obtain about 20 microg of pure
      product which is not enough for NMR analysis. Detailed GC-MS analytical data of
      the methylated compounds indicated that these oligosaccharides were beta-D-Fru-(2
      --> 1)-beta-D-Fru-(2 --> 1)-alpha-D-glucopyranoside (1-kestose), beta-D-Fru-(2 -
      > 6)-alpha-D-glucopyranoside (6-beta fructofuranosylglucose), beta-D-Fru-(2 -->
      1)-beta-D-fructofuranoside (inulobiose), beta-D-Fru-(2 --> 6)-beta-D-Fru-(2 -->
      1)-alpha-D-glucopyranoside (6-kestose) and beta-D-Fru-(2 --> 6)-alpha-D-Glc-(1 -
      > 2)-beta-D-fructofuranoside (neokestose) coeluating with a disaccharide.

PMID- 11453014
TI  - Effect of temperature on retention and selectivity in ion chromatography of
      anions.
AB  - The temperature dependence of retention of a wide range of inorganic anions is
      studied on two commercially available ion exchangers (Dionex AS11 and AS14
      columns). Anion retention exhibited both exothermic and endothermic behavior,
      such that varying the temperature from ambient to 60 degrees C produced
      selectivity changes. The anions displayed three groupings of temperature
      dependence: weakly retained singly charged anions (e.g., iodate, bromate,
      nitrite, bromide and nitrate); multiply charged anions (sulfate, oxalate,
      phosphate and thiosulfate); and strongly retained singly charged anions (iodide,
      thiocyanate and perchlorate). Temperature was ineffective at changing the
      selectivity of retention between anions of the same grouping. However,
      significant selectivity changes, including elution order reversal, could be
      achieved between anions from different groupings.

PMID- 11453015
TI  - Behaviour of inorganic and organic cations in the Debye-Huckel layer of DNA.
AB  - Inorganic, monovalent cations (Li, Na, K, Rb, Cs), when present in the Debye
      Huckel layer of DNA, are found to bind to the negatively charged groups of the
      helix solely on the basis of their charge/mass ratio. Thus, when an electric
      field is applied, the free mobility of the DNA is seen to increase from Li- to Cs
      equilibrated DNAs, since the latter cation, having a weaker surface charge
      distribution and a larger physical size (in the non-hydrated state), is more
      loosely bound to the DNA helix, thus providing less screening of its negative
      charges. On the contrary, organic amines (Tris and a number of Good's buffers)
      are found to bind not only via electrostatic interactions, but by additional
      bonds, notably H-bonds. In particular, Tris can form two H-bonds, with a purine
      and pyrimidine, respectively, and a third H-bond shared between the -OH groups of
      two adjacent Tris. Hence, these buffer components may be unwitting participants
      in reactions carried out in in vitro systems.

PMID- 11453016
TI  - Optimisation of the separation of anions by ion chromatography-capillary
      electrophoresis using indirect UV detection.
AB  - The separation of a complex mixture of inorganic and organic anions by ion
      chromatography-capillary electrophoresis using a cationic polymer added to the
      background electrolyte and indirect UV detection has been studied. The addition
      of unmodified polymer to an electrolyte suitable for indirect detection resulted
      in the appearance of a system peak due to the counter-anion on the polymer and
      while the position of the analytes relative to this system peak could be changed,
      this was found to be an unacceptable approach for mixtures of large numbers of
      analytes. Although conversion of the polymer to replace the counter-ion with the
      indirect UV detection probe ion simplified the system, this approach restricted
      the flexibility of the system because the probe and polymer concentration were
      necessarily linked. This limitation could be overcome by selecting the
      appropriate type of probe ion, with probes having a low ion-exchange selectivity
      coefficient providing greater retention of analytes than probes with a high ion
      exchange selectivity coefficient. Three electrolyte systems with different probes
      (benzoate, chromate and phthalate) were modelled using a previously derived
      migration equation and this was used to optimise the electrolyte composition to
      enable the separation of a mixture of 24 inorganic and organic anions within 7
      min. The electrolyte composition was then optimised for the analysis of anions in
      Bayer liquor with the final separation selectivity being substantially improved
      for selected key analytes.

PMID- 11453017
TI  - Simultaneous control of electrostatic micellar partition and electroosmotic flow
      rate by anion-dominated partition into zwitterionic micelles.
AB  - The zeta potentials of zwitterionic micelles and capillary walls have been
      evaluated with capillary electrophoresis. The zeta potential of the micelles is
      predominantly determined by the nature of anions, while cations of identical
      valence have marginal effects; the linear relation has been found between the
      induced zeta potential and the hydration energy of an anion. The zeta potential
      of the capillary wall is also varied with anionic natures, and there is a good
      correlation between micellar and capillary wall zeta potential. This strongly
      suggests that the zeta potential of capillary walls is determined by the
      partition of anions into the surfactant layer formed on the capillary wall. Thus,
      we can simultaneously control both the electroosmotic flow-rate and micellar
      surface potential (in turn electrostatic interaction between micelles and ionic
      solutes) by varying the type and concentration of electrolytes. This idea has
      been applied to the separation of aromatic cationic solutes.

PMID- 11453018
TI  - Capillary electrophoresis for measuring major and trace anions in thermal water
      and condensed-steam samples from hydrothermal springs and fumaroles.
AB  - A new application of capillary electrophoresis for measuring major and trace
      anions in thermal water and condensed-steam samples is presented. Ten fluid
      samples were collected from hydrothermal springs and fumaroles located in a
      volcanic zone of Deception Island, Antarctica. Anion separation was achieved in
      less than 6 min using indirect UV detection at 254 nm with a negative power
      supply (-15 kV). The electrolyte consisted of 4.7 mM sodium chromate, 4.0 mM
      electroosmotic flow modifier (OFM) hydroxide, 10 mM 2-(N
      cyclohexylamino)ethanesulfonic acid and 0.1 mM calcium gluconate (pH 9.1). Major
      anions (Cl-, SO4(2), PO4H2+, and CO3H-) were measured using hydrostatic injection
      (10 cm for 30 s) at 25 degrees C. Trace amounts of anions (F-, Br-, and NO3-)
      were better determined by electromigration injection (4 kV, 10 s) at 15 degrees
      C. Good reproducibility of the migration times (<0.72% RSD), a satisfactory
      linear response and accuracy as well as acceptable detection limits were
      successfully obtained.

PMID- 11453019
TI  - Determination of quaternary alkylammonium compounds by capillary zone
      electrophoresis and indirect UV detection as a real alternative to ion
      chromatography with suppressed conductivity detection.
AB  - A capillary electrophoretic (CE) method for the determination of residual mid
      chain alkyltrimethylammonium compounds in the pharmaceutical product Welchol (an
      alkylated, crosslinked polyallylamine) was developed, validated and compared with
      the existing ion chromatographic (IC) method with suppressed conductivity
      detection. Excellent reproducibilities of migration times (RSD<0.5% within a
      series of 55 sample injections) and relative peak areas (RSD<2%) make the method
      suitable for quality control as a real alternative to IC. Limits of
      quantification of 0.01% w/w of each impurity in the active substance were
      achieved. Buffer systems for indirect UV detection based on creatinine as
      visualization reagent with different inorganic and organic acids (phosphoric,
      sulfuric, formic, acetic, oxalic and citric acid) and their effect on selectivity
      to ten quaternary ammonium compounds were studied. Selectivity changes were
      observed for the di- and trivalent analytes depending on the buffer applied.
      Also, the influence of acetonitrile, methanol, 1,4-dioxane and tetrahydrofuran on
      selectivity was investigated. In addition, CE-MS experiments were carried out in
      order to identify several impurities in the product.

PMID- 11453020
TI  - Determination of C4-C14 carboxylic acids by capillary zone electrophoresis.
      Application to the identification of diamide degradation products and
      partitioning studies.
AB  - Capillary zone electrophoresis (CZE) was investigated for the determination of
      linear saturated carboxylic acid homologues ranging from C4 to C14. Separation
      conditions were optimised to overcome the problems of decreasing solubility and
      decreasing selectivity between successive homologues with increasing chain
      length. Separations were performed at 20 degrees C, using a 20 kV separation
      voltage and a pH 8 electrolyte containing 30% methanol. A suitable chromophore (4
      aminobenzoate) was added to ensure indirect UV detection of the analytes.
      Calibration curves and repeatability were established. Minimum detectable
      concentrations of 3 x 10(-6) mol l(-1) were achieved. Resolution between
      successive homologues was better than 2. The electrophoretic mobility of each
      homologue (n=7-14) was assessed and a quasi-linear relationship between the
      mobility value and 1/n was observed. The quantitative analysis of a diamide
      degradation solution was performed and compared to potentiometric results. The
      CZE method was also applied to the determination of C7-C14 partitioning between
      an organic medium containing tributylphosphate in n-dodecane and different basic
      solutions. Their behaviour was established according to the chain length and the
      pH of the aqueous phase. For C10-C14 compounds, results were validated by
      comparison with gas chromatographic analysis of the organic phases.

PMID- 11453021
TI  - High-sensitivity determination of the degradation products of chemical warfare
      agents by capillary electrophoresis-indirect UV absorbance detection.
AB  - Capillary electrophoresis coupled with indirect UV absorbance detection was
      employed for the determination of the chemical warfare agent degradation
      products: methylphosphonic acid, ethyl methylphosphonate, isopropyl
      methylphosphonate, and pinacolyl methylphosphonate. Glutamic acid was used as a
      buffering agent at its isoelectric point (pH 3.22). In its zwitterionic form,
      glutamic acid does not act as a competing co-anion in the system, thus providing
      buffering capacity while maintaining high sensitivity. The indirect probe
      (phenylphosphonic acid) concentration was lowered to 1 mM from the 10 mM in
      previous literature studies, further enhancing sensitivity. Detection limits of 2
      microM were achieved with hydrodynamic injection and up to 100-fold lower using
      electrokinetic injection. The increased buffering capacity of this system over
      previous methods led to migration time reproducibility RSD values of 0.18 to
      0.22%. This represents a 10-fold improvement in reproducibility over previous
      studies with comparable or improved sensitivity.

PMID- 11453022
TI  - Capillary-electrochromatographic separations with copolymeric reversed-stationary
      phase and ion-exchanger-packed columns.
AB  - A macroporous, spherical, 7 microm, polystyrene-divinylbenzene (PS-DVB), reversed
      phase adsorbent (PRP-1) was evaluated as a stationary phase for the capillary
      electrochromatographic (CEC) separation of neutral, acidic, and basic analytes of
      pharmaceutical interest. Electroosmotic flow (EOF) for a PRP-1 packed capillary
      is nearly constant over the pH 2 to 10 range and is higher than for a silica
      based C18 packed capillary on the acidic side. EOF increases with an increase in
      buffer acetonitrile concentration or as applied potential increases. As analyte
      hydrophobicity increases, analyte retention and migration time increases.
      Increasing buffer acetonitrile concentration reduces analyte partitioning with
      the PS-DVB stationary phase and analyte retention and migration time decreases.
      When exchange sites are present on the PS-DVB copolymer, EOF (EOF is reversed for
      the anion-exchanger) increases as the exchange capacity increases. An increased
      exchange capacity also reduces partitioning of the analyte with the PS-DVB matrix
      and analyte retention and migration time decrease. Because of excellent stability
      in an acid environment, the PRP-1 packed capillary can be used in strong acid
      buffer solution and weak acid and base analytes depending on pKa values can be
      separated as neutral species and cations, respectively. CEC separations on a PRP
      1 capillary of neutral steroids, weak base pharmaceuticals (separation as
      cations), purines and pyrimidines (as cations), fatty acids (as undissociated
      species), and sulfa derivatives (as cations) are described. Efficiency for the
      PRP-1 packed capillary for acetone or thiourea as the analyte is about 6 x 10(4)
      plates m(-1).

PMID- 11453023
TI  - Retention modelling of electrostatic and adsorption effects of aliphatic and
      aromatic carboxylic acids in ion-exclusion chromatography. II. Calculations of
      adsorption coefficients in unbuffered eluents.
AB  - Previous models for the retention behaviour of carboxylic acids in ion-exclusion
      chromatography are applicable only when the degree of ionisation of the analyte
      is constant over the entire chromatographic peak. When solutions of sulfuric acid
      are used as eluents, this condition applies only when the eluent concentration is
      considerably higher than that of the analyte. Since it is common for dilute
      solutions of sulfuric acid to be used as eluents, a retention model which
      accounts for unbuffered eluents has been developed. This model also considers the
      effects on retention of hydrophobic adsorption of the undissociated and
      dissociated forms of the analyte onto the stationary phase substrate, as well as
      the effects of organic solvents added to the eluent. The derivation of this model
      is presented and it has been evaluated using a comprehensive set of retention
      data obtained using three different sulfonated stationary phases over a range of
      eluent conditions. The adsorption coefficients calculated from the model are in
      accordance with expected trends and showed that both the undissociated and
      dissociated forms of the analyte acids were retained by hydrophobic adsorption
      effects, although this adsorption was much stronger for the undissociated
      analytes.

PMID- 11453024
TI  - New block-grafted anion exchanger for environmental water analysis by ion
      chromatography.
AB  - The IonPac AS14A is a recently developed stationary phase that was produced using
      a new block-grafting technique, which enables the preparation of high-water
      content anion exchangers with excellent peak shape and good chromatographic
      efficiency. The performance of this column for the analysis of inorganic anions
      was compared to that obtained using an IonPac AS4A column, which is specified in
      US Environmental Protection Agency Method 300.0, in addition to another commonly
      used alternative: the AS14 column. The AS14A column is available in two different
      formats: 250x4 mm I.D. (7.0 microm diameter particle) and 150x3 mm I.D. (5.5
      microm diameter particle). The IonPac AS14A (in 4 mm I.D. format) was found to
      provide similar performance to the AS14 column with increased peak efficiency and
      better pH stability and is a suitable alternative for the analysis of anions in
      moderate- to high-ionic-strength samples. The IonPac AS14A (in 3 mm I.D. format)
      provides comparable run times to the AS4A column with better overall peak
      selectivity and improved fluoride resolution, hence this column would be a
      suitable column to substitute in place of either the AS4A or AS14 columns for the
      analysis of inorganic anions in low- to moderate-ionic-strength environmental
      waters. The AS14A column used with an Atlas electrolytic suppressor provides
      equivalent method detection limits to those obtained when using a micromembrane
      suppressor but with the operational convenience of a self-regenerating
      suppressor.

PMID- 11453025
TI  - High-capacity cation-exchange column for enhanced resolution of adjacent peaks of
      cations in ion chromatography.
AB  - One of the advantages of ion chromatography [Anal Chem. 47 (1975) 1801] as
      compared to other analytical techniques is that several ions may be analyzed
      simultaneously. One of the most important contributions of cation-exchange
      chromatography is its sensitivity to ammonium ion, which is difficult to analyze
      by other techniques [J. Weiss, in: E.L. Johnson (Ed.), Handbook of Ion
      Chromatography, Dionex, Sunnyvale, CA, USA]. The determination of low
      concentrations of ammonium ion in the presence of high concentrations of sodium
      poses a challenge in cation-exchange chromatography [J. Weiss, Ion
      Chromatography, VCH, 2nd Edition, Weinheim, 1995], as both cations have similar
      selectivities for the common stationary phases containing either sulfonate or
      carboxylate functional groups. The task was to develop a new cation-exchange
      stationary phase (for diverse concentration ratios of adjacent peaks) to overcome
      limitations experienced in previous trails. Various cation-exchange capacities
      and column body formats were investigated to optimize this application and
      others. The advantages and disadvantages of two carboxylic acid columns of
      different cation-exchange capacities and different column formats will be
      discussed.

PMID- 11453026
TI  - Application of zirconium-modified silica gel as a stationary phase in the ion
      exclusion chromatography of carboxylic acids. I. Separation of benzenecarboxylic
      acids with tartaric acid as eluent and with UV-photometric detection.
AB  - The application of zirconium-modified silica gels (Zr-Silicas) as stationary
      phases for ion-exclusion chromatography with UV-photometric detection (IEC-PD)
      for mono-, di-, tri- and tetrabenzenecarboxylic acids (pyromellitic, trimellitic,
      hemimellitic, o-phthalic, salicylic and benzoic acids) and phenol was carried out
      using tartaric acid as the eluent. Zr-Silicas were prepared by the reaction of
      the silanol group on the surface of silica gel with zirconium tetrabutoxide
      [Zr(OCH2CH2CH2CH3)4] in ethanol solution. The effect of the amount of zirconium
      adsorbed on silica gel on chromatographic behavior of these benzenecarboxylic
      acids and phenol was investigated. As a result, Zr-Silica adsorbed on 20 mg
      zirconium g(-1) silica gel was the most suitable stationary phase in the IEC-PD
      for the simultaneous separation of these benzenecarboxylic acids and phenol.
      Excellent simultaneous separation and highly sensitive UV detection at 254 nm for
      these benzenecarboxylic acids and phenol were achieved in 20 min by the IEC-PD
      using the Zr-Silica column (250x4.6 mm I.D.) and a 10 mM tartaric acid at pH 2.5
      as eluent.

PMID- 11453027
TI  - Ion-exchange properties of hypercrosslinked polystyrene impregnated with methyl
      orange.
AB  - A novel bipolar stationary phase (HCPS-MO) was prepared by impregnation of
      hypercrosslinked polystyrene (HCPS) with methyl orange (MO; 4-dimethylamino-4'
      sulfoazobenzene) and its ion-exchange properties were studied. Simultaneous
      separation of cations and anions on HCPS-MO is possible, although it behaves
      preferentially as a cation-exchanger. Unusual selectivity of HCPS-MO for alkali
      and alkaline-earth metal cations: Na+ < Li+ approximately = K+ < Rb+ < NH4+ < Cs+
      and Mg2+ < Sr2+ < Ca2+ < Ba2+ was observed. The effect of temperature on
      retention of alkali and alkaline-earth metal cations was studied. Separation of
      Na+, K+, Rb+, NH4+, Cs+, Mg2+ and Ca2+ on HCPS-MO with diluted cerium(III)
      nitrate solution as an eluent in single run is presented.

PMID- 11453028
TI  - Novel stationary phase with regulated anion-exchange capacity.
AB  - A novel stationary phase--phenylaminopropyl (PLA) bonded silica--is proposed for
      anion-exchange chromatography. Low basicity (pKA about 2.5) attached to silica
      phenylaminopropyl groups allows a variation of surface density of protonated
      sites in the pH range from 2 to 5. This enables us to use the same column for the
      separation of anions having different affinity to anion-exchangers. The effect of
      mobile phase pH on conditional capacity of PhA-silica was studied. The hypothesis
      on dependence of ion-exchange selectivity on the column capacity is discussed.
      Suitability of PhA-silica for ion-chromatographic separation of organic and
      inorganic anions at different pH values of eluent was demonstrated.

PMID- 11453029
TI  - Manipulation of separation selectivity of inorganic anions in electrostatic ion
      chromatography by the use of mixed cationic-zwitterionic micelles as the column
      coating solution.
AB  - This paper describes an electrostatic ion chromatographic system in which the
      separation selectivity for inorganic anions, especially for sulfate and
      phosphate, could be manipulated by altering the molar ratio of the zwitterionic
      and cationic surfactants in the column coating solution used to prepare the
      stationary phase. The zwitterionic surfactant used for this study was 3-(N,N
      dimethyltetradecylammonio)propanesulfonate (Zwittergent-3-14) and the cationic
      surfactant was tetradecyltrimethylammonium (TTA). Using a reversed-phase C18
      column (250x4.6 mm I.D.) coated with 10/10 (mM/mM) of TTA/Zwittergent-3-14 mixed
      micelles as the stationary phase and either NaHCO3 or Na2CO3 aqueous solution as
      the eluent, together with suppressed conductivity detection, baseline separation
      of seven model inorganic anions was obtained. The elution order for those anions
      was found to be F+ < HPO4(2-) < Cl- < SO4(2-) < NO2- < Br- < NO3-. Under the same
      conditions but using 1/10 (mM/mM) of TTA/Zwittergent-3-14 mixed micelles as the
      column coating solution, the elution order for these model ions was F- < HPO4(2-)
      < SO4(2-) < Cl- < NO2- < Br- < NO3-. The early elution of phosphate and sulfate
      is a unique attribute of this system. Detection limits for F-, HPO4(2-), Cl-,
      SO4(2-), NO2-, Br- and NO3- (S/N=3, sample injection volume 100 microl) were
      0.11, 0.12, 0.12, 0.18, 0.49, 0.49, 0.52 microM, respectively.

PMID- 11453030
TI  - Changes in the control of gonadotrophin secretion by neurotransmitters during
      sexual development in rats.
AB  - Gonadotrophin hormone releasing hormone (GnRH) is the primary messenger involved
      in sexual maturation and the onset of puberty. The activity of these neurons are
      controlled by several neurotransmitters systems. The onset of puberty implies
      changes from a prepubertal type of gonadotrophin secretion, characterized by a
      low activity of GnRH neurons, to an adult pattern of secretion with phasic and
      synchronous activation of GnRH neurons resulting in an increase in the amplitute
      and frequency of GnRH pulses. Neurotransmitter systems are involved in these
      changes of GnRH secretion during the onset of puberty by quantitative and
      qualitative modifications in the effect on GnRH secretion. Serotonin (5-HT), GABA
      and catecholamines (CA) have qualitative differences in the effects on GnRH and
      LH secretion in early prepubertal than in late prepubertal and adult female rats.
      The administration of 5-hydroxytryptophan a precursor of serotonin (5-HT) which
      increases 5-HT hypothalamic levels induces GnRH and LH release in early
      prepubertal female rats, these effects dissapear in late prepubertal stage having
      an inhibitory action in adult female rats. GABAergic system also stimulates GnRH
      and LH secretion in early prepubertal female rats and has an inhibitory action on
      this axis in late prepubertal period and in adult female rats. On the contrary
      the inhibition of catecholamines synthesis by alpha-methyl-p-tyrosine induced an
      increase of LH secretion in early prepubertal female rats and inhibitory effect
      in late prepubertal and adult stage. These effects indicate tha CA has an
      inhibitory effects on GnRH-LH secretion in early prepubertal female rats changing
      to an stimulatory action in the late puberty and adult rats. These qualitative
      modifications were observed only in female rats and are probably connected with
      the hypothalamic differentiation into a female type of gonadotrophin control.
      Opiadergic and excitatory amino acid systems have quantitative differences on
      GnRH-LH secretion during prepubertal and peripubertal and adult stages. Opiates
      has an high inhibitory tone in early prepubertal rats that is decreasing during
      sexual maturation to reach puberty. On the contrary EAA increases its stimulatory
      activity on GnRH-LH secretion during sexual maturation by increasing the
      hypothalamic release of aspartate and glutamate, the excitatory amino acids
      involved in GnRH release, and the sensibility of NMDA receptors to these amino
      acids. In conclusion sexual maturation and the onset of puberty in the female
      rats involve qualitative and quantitative modifications in the effects of
      neurotrasmitters system on GnRH secretion.

PMID- 11453031
TI  - Insulin treatment improves islet function in type 2 diabetic Chinese hamsters.
AB  - To study whether normalization of hyperglycemia improves islet function in long
      standing type 2 diabetes, hyperglycemic CHIG/Han subline of the genetic type 2
      diabetic Chinese hamster (>15 mmol/l: n=23) were either treated with insulin
      implants (liberating 1 U/day) or vehicle for two weeks. Islets were isolated and
      incubated for 3 h in the presence of 10 mmol/l glucose with or without 0.1 mmol/l
      3-isobutyl-1-methylxanthine (IBMX). Specimens were also taken for
      immunocytochemical analysis of insulin cells. Glucose-stimulated insulin
      secretion was reduced by 83% in the vehicle-treated diabetic hamsters compared to
      non-diabetic controls (p<0.001). This impairment was not improved by the two-week
      insulin treatment. IBMX potentiated glucose-stimulated insulin secretion; this
      effect was markedly reduced in vehicle-treated diabetics compared to controls
      (p<0.001). In fact, the linear relation between IBMX-potentiated and glucose
      stimulated insulin secretion in controls was absent in islets from diabetic
      animals. The two week insulin treatment normalized this relation, although still
      the total insulin secretory response to IBMX and glucose was lower than in
      controls. Furthermore, the islet insulin content was significantly increased by
      the 2 week normalization of glucose and, finally, the severe degranulation and
      lowering of insulin staining in islet beta cells in diabetic animals were
      markedly improved by insulin treatment. The results suggest that two-weeks of
      normalization of glycemia in long-standing type 2 diabetes in non-obese Chinese
      hamster improves beta cell signaling induced by the cyclic AMP pathway in
      conjunction with improved islet insulin content and beta cell morphology.

PMID- 11453032
TI  - Troglitazone and rosiglitazone inhibit the low density lipoprotein-induced
      vascular smooth muscle cell growth.
AB  - Troglitazone (TRO) and rosiglitazone (RSG) belong to the thiazolidinedione class
      (insulin-sensitizing agents) and exert many of their metabolic effects as
      peroxisome proliferator-activated receptor gamma (PPARgamma) ligands. In the
      present study we examined the effects of TRO and RSG on LDL-induced VSMC growth.
      Pretreatment of VSMC with 1 microM TRO or 0.1 microM RSG completely blocked the
      LDL-induced cell proliferation as measured by [3H]thymidine incorporation into
      DNA and by determination of the cell number. We then examined with Western
      blotting whether these growth suppressing effects are mediated through the
      mitogen-activated protein kinase (MAPK) pathway, a common signaling pathway
      activated by growth factors. TRO and RSG had no effect on the LDL-induced
      stimulation of the MAP kinases ERK1/2, p38 and SAP/JNK. We conclude that
      thiazolidinediones are potent inhibitors of LDL-induced VSMC growth acting
      downstream of the cytoplasmic activation of MAPK.

PMID- 11453033
TI  - Relationship between plasma soluble thrombomodulin levels and insulin resistance
      syndrome in type 2 diabetes: a comparison with von Willebrand factor.
AB  - Endothelial dysfunction plays a pivotal role in the initial stage of
      atherosclerosis. Insulin resistance is associated with accelerated
      atherosclerosis, especially coronary heart disease. To elucidate the relationship
      between endothelial dysfunction and insulin resistance or insulin resistance
      syndrome in patients with type 2 diabetes, we investigated the correlation
      between plasma soluble thrombomodulin (TM) and von Willebrand factor (vWF),
      measures of endothelial dysfunction, and the degree of insulin resistance
      evaluated by homeostasis assessment models of insulin resistance (HOMA-IR), or
      variables of insulin resistance syndrome. We studied 53 patients with type 2
      diabetes, 23 treated with diet alone and 30 treated with sulfonylureas, who had
      normal renal function. The plasma soluble TM concentrations were highly
      correlated with HOMA-IR (r=0.64, p<0.0001), the plasma insulin (r=0.72,
      p<0.0001), the systolic blood pressure (r=0.45, p=0.0005), and the plasma
      fibrinogen (r=0.43, p=0.0018), while they were inversely correlated with the
      serum HDL cholesterol concentrations (r=-0.27, p=0.0344). The plasma vWF
      concentrations were positively correlated with HOMA-IR (r=0.35, p=0.0151) and the
      plasma fibrinogen (r=0.32, p=0.0203), but not with the plasma insulin, the
      systolic blood pressure or the HDL cholesterol concentrations. Furthermore,
      plasma TM, but not vWF, was positively correlated with total number of variables
      of insulin resistance syndrome (r=0.45, p=0.0005). These results indicate that
      endothelial dysfunction may be associated with the pathogenesis of insulin
      resistance syndrome as well as insulin resistance, and that the plasma TM might
      reflect endothelial damage better than the plasma vWF in the state of insulin
      resistance in patients with type 2 diabetes.

PMID- 11453034
TI  - TGFbeta1 and TGFbeta2 mRNA and protein expression in human bone samples.
AB  - Transforming growth factor beta is one of the most abundant growth factors stored
      in bone. It is known as a potent regulator of osteoblast proliferation and
      differentiation as well as of production extracellular matrix. We established a
      highly specific RT-PCR in combination with HPLC for detection and quantification
      of TGFbeta1 and TGFbeta2 mRNA expression in 89 human bone samples. Levels of
      TGFbeta1 protein ranged between 27 and 580 ng/g bone (mean 188 +/- 15 ng/g; n=75)
      and for TGFbeta2 between 7.2 and 35 ng/g bone (mean 14.3 +/- 2.1 ng/g; n=57).
      TGFbeta1 and TGFbeta2 protein concentrations and TGFbeta isoform mRNA expression
      in bone were not significantly different between the sexes. TGFbeta isoform mRNA
      expression as well as protein content in bone declined age dependently. TGFbeta1
      and TGFbeta2 protein and mRNA expression were different in bone samples from
      different sites of the skeleton indicating in part the regulation by mechanical
      stimuli. In contrast to TGFbeta1, TGFbeta2 mRNA expression was significantly
      enhanced in osteoarthritic bone compared to unaffected bone. These data are in
      concordance to previous results concerning the expression of TGFbeta3 in bone. In
      conclusion, the data suggest distinct patterns' of expression of the TGFbeta
      isoforms under physiological and pathological conditions in bone.

PMID- 11453035
TI  - 11Beta-hydroxysteroid dehydrogenase bioactivity is increased in the colon but not
      kidneys of rats given supplementary thyroxine.
AB  - The aim of this study was to investigate the effect of altered thyroid status on
      11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD type 1) and type 2 (11beta
      HSD type 2) bioactivity in rat kidney and colon. Male Sprague-Dawley rats (250 g)
      were treated with either L-thyroxine (T4) or propylthiouracil (PTU) for 4 weeks.
      Blood were then analysed for serum thyroxine, sodium (Na+) and potassium (K+).
      The kidneys and colon were assayed for 11beta-HSD type 1 and 11beta-HSD type 2
      bioactivity. In T4 treated rats the serum thyroxine was significantly elevated
      (p<0.05) whilst PTU decreased serum thyroxine significantly (p<0.001) compared to
      controls. Serum Na+ and K+ were within normal limits. There were no significant
      changes in 11beta-HSD type 1 bioactivity in both treatment groups compared to
      controls. However, the 11beta-HSD type 2 bioactivity in rats given thyroxine was
      significantly higher in the colon (p<0.003) compared to controls. We conclude
      that altered thyroid status had no effect on 11beta-HSD type 1 bioactivity but
      11beta-HSD type 2 bioactivity was elevated in the colon of rats given
      supplementary thyroxine.

PMID- 11453036
TI  - Regulation of estrogen receptor alpha and progesterone receptor (isoform A and B)
      expression in cultured human endometrial cells.
AB  - The effects of RU 486 together with estradiol and progesterone on estrogen
      receptor alpha and progesterone receptor (isoforms A and B) expression were
      studied in human endometrial long term cultures at the mRNA and protein level. We
      asked whether ligand induced receptor regulation, found in mammals in vivo, is
      also found in human cultured endometrial cells with special regard to the
      progesterone isoforms A and B. Endometrial cultures were maintained for 27 days.
      Media were supplemented with progesterone and/or estradiol alone or in
      combination with RU 486. Receptor expression (estrogen receptor alpha and
      progesterone receptor isoform A and B) was examined at the mRNA level by RT-PCR
      and at the protein level by western blot analysis. All receptor types examined
      were expressed in our culture model. Estradiol led to a general increase of
      receptor expression whereas treatment with estradiol in combination with
      progesterone down regulated receptor expression. The receptor down regulation was
      not found when RU 486 was additionally supplemented into the medium. Activation
      or inhibition of expression due to these treatments was similar for both PR
      isoforms. Our results (1) show that in our culture system estradiol induced up
      regulation of estrogen receptor and progesterone receptor A and B and suggest
      that the estrogen induced up regulation is prevented by progesterone (2) a clear
      cut antigestagenic effect of RU 486 and (3) suggest that both progesterone
      isoforms are analogously regulated in our culture model. We conclude that human
      endometrial cell cultures are suitable for the study of the dynamics of steroid
      receptor expression.

PMID- 11453037
TI  - Differential distribution of estrogen receptor-beta and estrogen receptor-alpha
      in the porcine ovary.
AB  - Steroids act on the follicle through autocrine and paracrine mechanisms to
      regulate follicular growth and steroidogenesis. Estradiol plays a significant
      role in determining the fate of the developing follicle and acts via specific
      receptors which are nuclear transcription factors. It has been established that
      besides classical estrogen receptor-alpha (ER alpha) novel forms termed ER beta
      exist. In species studied to date these two types of ERs exhibit different tissue
      localisation patterns and levels of expression. The present study was performed
      to determine whether ER alpha and ER beta are differentially expressed in the
      porcine ovary. Immunohistochemical studies using antibodies to ER alpha and ER
      beta, established the predominance of ER beta over ER alpha in the porcine ovary.
      Cyclical changes in estrogen receptor-beta expression were observed. The
      immunostaining was present in all types of follicles, and decreased in corpus
      luteum while it regressed. In the contrary estrogen receptor-alpha staining was
      seen only in large preovulatory follicle and in early corpora lutea.

PMID- 11453038
TI  - Severe hypoglycemia due to insulin autoimmune syndrome with insulin
      autoantibodies crossreactive to proinsulin.
AB  - We report the case of a 69-year-old woman with insulin autoimmune syndrome first
      misdiagnosed as insulinoma. The case demonstrates the difficulties to correctly
      diagnose this rare disorder as both insulin and proinsulin levels were increased
      by crossreactive autoantibodies. No known triggering agent could be identified.
      We suggest that this diagnosis should be considered more often also in caucasian
      patients to avoid useless operations for such patients.

PMID- 11453039
TI  - Triglycerides, fatty acids and insulin resistance--hyperinsulinemia.
AB  - There is now much interest in the mechanisms by which altered lipid metabolism
      might contribute to insulin resistance as is found in Syndrome X or in Type II
      diabetes. This review considers recent evidence obtained in animal models and its
      relevance to humans, and also likely mechanisms and strategies for the onset and
      amelioration of insulin resistance. A key tissue for development of insulin
      resistance is skeletal muscle. Animal models of Syndrome X (eg high fat fed rat)
      exhibit excess accumulation of muscle triglyceride coincident with development of
      insulin resistance. This seems to also occur in humans and several studies
      demonstrate increased muscle triglyceride content in insulin resistant states.
      Recently magnetic resonance spectroscopy has been used to demonstrate that at
      least some of the lipid accumulation is inside the muscle cell (myocyte). Factors
      leading to this accumulation are not clear, but it could derive from elevated
      circulating free fatty acids, basal or postprandial triglycerides, or reduced
      muscle fatty acid oxidation. Supporting a link with adipose tissue metabolism,
      there appears to be a close association of muscle and whole body insulin
      resistance with the degree of abdominal obesity. While causal relationships are
      still to be clearly established, there are now quite plausible mechanistic links
      between muscle lipid accumulation and insulin resistance, which go beyond the
      classic Randle glucose-fatty acid cycle. In animal models, dietary changes or
      prior exercise which reduce muscle lipid accumulation also improve insulin
      sensitivity. It is likely that cytosolic accumulation of the active form of lipid
      in muscle, the long chain fatty acyl CoAs, is involved, leading to altered
      insulin signalling or enzyme activities (eg glycogen synthase) either directly or
      via chronic activation of mediators such as protein kinase C. Unless there is
      significant weight loss, short or medium term dietary manipulation does not alter
      insulin sensitivity as much in humans as in rodent models, and there is
      considerable interest in pharmacological intervention. Studies using PPARgamma
      receptor agonists, the thiazolidinediones, have supported the principle that
      reduced muscle lipid accumulation is associated with increased insulin
      sensitivity. Other potent systemic lipid-lowering agents such as PPARalpha
      receptor agonists (eg fibrates) or antilipolytic agents (eg nicotinic acid
      analogues) might improve insulin sensitivity but further work is needed,
      particularly to clarify implications for muscle metabolism. In conclusion,
      evidence is growing that excess muscle and liver lipid accumulation causes or
      exacerbates insulin resistance in Syndrome X and in Type II diabetes; development
      of strategies to prevent this seem very worthwhile.

PMID- 11453040
TI  - Postprandial triglycerides and blood coagulation.
AB  - Most of our lifetime we spend in the postprandial state. Postprandial
      triglyceridemia may represent a procoagulant state involving disturbances of both
      blood coagulation and fibrinolysis, in particular due to elevation of the plasma
      levels of activated factor VII (VIIa) and plasminogen activator inhibitor (PAI
      1). Therefore, disturbances of the hemostatic system might, at least partly,
      account for by the link between hypertriglyceridemia and coronary heart disease
      (CHD). Factor VIIa is the first enzyme of the blood coagulation system and serves
      a priming function for triggering of the clotting cascade. The coagulant activity
      of factor VII (VIIc, total activity of factor VII in plasma) was identified as an
      independent predictor of myocardial infarction in initially healthy middle-aged
      men, and particularly of fatal coronary events, and both serum cholesterol and
      triglyceride concentrations correlated positively with the VIIc level. Addition
      of fat to diet has been consistently shown to cause a rapid conversion of the
      factor VII zymogen into its active form (VIIa) whereas the concentration of total
      protein is unaffected. Postprandial activation of factor VII is dependent on
      lipolytic activity and it is mainly supported by large triglyceride-rich
      lipoprotein of the VLDL class. Studies in vivo with specific coagulation factor
      deficient patients indicate that factor IX is essential for the postprandial
      activation of factor VII. The basal generation of thrombin seems to be unaffected
      by increased plasma levels of VIIa. However, since VIIa-tissue factor complex is
      responsible for the initiation of the coagulation cascade, increased generation
      of VIIa in the postprandial state would increase the potential for thrombin
      production in the event of plaque rupture. Plasminogen activator inhibitor-1 (PAI
      1) is the major physiological inhibitor of the plasminogen activators in the
      circulation and thereby the principal inhibitor of the fibrinolytic system.
      Postprandial triglyceridemia has been observed in many, not all, studies to
      increase PAI-1 plasma levels, which would further strengthen the chances of
      thrombotic occlusion of a vessel after rupture of an atherosclerotic plaque.

PMID- 11453041
TI  - Postprandial triglycerides and endothelial function.
AB  - Several studies support the association between postprandially elevated
      triglyceride levels and atherosclerosis. Histological and cell culture
      investigations revealed, that triglyceride rich postprandial lipoproteins are
      taken up by macrophages and smooth muscle cells and are detectable as part of
      foam cells in vascular lesions. Remnant particles, generated by lipolysis of
      postprandial lipoproteins in vitro and fatty acids increase the permeability of
      the endothelium and are cytotoxic for endothelial cells. Besides these
      morphological changes of cells, lipoproteins have been shown to exert effects on
      cellular functions like the expression of membrane proteins and the production or
      release of several bioactive substances regulating communication with blood cells
      and other cell systems of the vascular wall, blood pressure and hemostasis. This
      review concentrates on the influence of postprandial lipoproteins on factors
      involved in the interaction of endothelial cells with blood leukocytes and
      factors mediating blood pressure regulation. Increased expression of adhesion
      molecules has been detected immunehistochemically in atherosclerotic plaques in
      animals and humans. It was demonstrated that patients with elevated triglyceride
      levels have increased levels of soluble adhesion molecules. Furthermore,
      postprandial lipoproteins were shown to induce membrane expression of adhesion
      molecules. This effect seems to be at least in part mediated by the oxidative
      modification of the particles. Accordingly chylomicrons separated after ingestion
      of safflower oil, rich in polyunsaturated linoleic acid, induced higher adhesion
      molecule expression at higher oxidant concentration compared with chylomicrons
      separated after ingestion of olive oil, rich in monounsaturated oleic acid.
      Several authors described effects of fatty acids on the expression of adhesion
      molecules. On the one hand, they may exert stimulatory effects as such, on the
      other hand cytokine induced adhesion molecule expression may be enhanced by
      certain fatty acids and inhibited by others, implying an interference with signal
      transduction processes. Effects of lipoproteins on vasoactive substances seem to
      be implicated in endothelial dysfunction, too. The endothelium-derived relaxing
      factor nitric oxide (NO) has gained increasingly attention in the last two
      decades and is regarded as protective against hypertension and atherosclerosis.
      It was demonstrated that chylomicrons and their remnants inhibited endothelium
      dependent relaxations in isolated aortas. Vasodilatatory responses and nitric
      oxide metabolism were shown to be affected by the amount and composition of
      dietary fat. Cell culture experiments revealed modulation of NO release by
      certain fatty acids. Plasma levels of endothelin-1, a strong vasoconstrictor,
      have been shown to be increased in patients with type 2 diabetes and metabolic
      syndrome, respectively. Postprandially elevated triglycerides increased
      endothelin-levels in addition to insulin in patients with metabolic syndrome. In
      summary, there is evidence that the association between postprandial
      triglycerides and the metabolic syndrome is driven by direct influences on
      endothelial functions because plasma triglyceride levels are associated with
      levels of humoral risk markers of endothelial origin, and postprandial
      lipoproteins stimulate the release and/or expression of endothelial mediators in
      vitro, which induce atherogenesis and hypertension.

PMID- 11453042
TI  - Treatment of dyslipoproteinemia in the metabolic syndrome.
AB  - The metabolic syndrome consists of a cluster of metabolic disorders, many of
      which promote the development of atherosclerosis and increase the risk to develop
      cardiovascular disease. The metabolic syndrome is characterized by atherogenic
      dyslipidemia (elevated triglycerides, increased small dense low-density
      lipoproteins, and decreased high-density lipoproteins), hypertension, insulin
      resistance and obesity. To decrease the risk of cardiovascular disease events
      decreasing body weight by ingesting a healthy diet, increasing physical activity,
      cessation of smoking and managing dyslipidemia are recommended. Pharmacological
      treatment of dyslipidemia is based on different drug classes. For LDL-cholesterol
      lowering mainly statins and for triglyceride-lowering mainly fibrates are used.
      In primary and secondary prevention trials of heart disease they have shown to
      reduce the incidence of coronary artery disease or coronary events by 25-60
      percent. Statins reduce mainly LDL-cholesterol levels by competitive inhibition
      of HMG-CoA reductase but have also shown to reduce fasting and postprandial
      triglyceride levels. Fibrates effectively reduce fasting and postprandial
      lipemia, shift the distribution of LDL particles towards less dense particles and
      increase HDL-cholesterol. Thus fibrates particularly address components of the
      metabolic syndrome and features of diabetic dyslipidemia. However studies still
      are needed showing definite evidence on differential therapy in lipid lowering
      based on prospective controlled trials with endpoints of macro- and
      microangiopathy in diabetic patients.

PMID- 11453043
TI  - Myocardial viability assessment in regions of left ventricular dysfunction. Part
      II: the present and future of echocardiography and magnetic resonance imaging.

PMID- 11453044
TI  - Clinical PET in the UK: dangers of missing an opportunity.

PMID- 11453045
TI  - Regional cerebral blood flow in normal individuals aged 40, 75 and 88 years
      studied by 99Tc(m)-d,l-HMPAO SPET.
AB  - Age-related changes in cerebral blood flow (CBF) were examined with [99Tc(m)]-d,l
      hexamethylpropylene amine oxime (HMPAO), using a single photon emission
      tomography (SPET) gamma camera system equipped with a high resolution collimator,
      in 33 normal individuals in three age groups: 40 years old (n = 11), 75 years old
      (n = 9) and 88 years old (n = 13). A standard activity of 1000 MBq [99Tc(m)]-d,l
      HMPAO was administered. Regional CBF (rCBF) (relative to cerebellar counts) was
      quantified in 28 grey and white matter regions. The mean rCBF of all the regions
      was 0.80 (95% confidence interval [CI] 0.77-0.83) in 40 year olds, 0.77 (0.74
      0.80) in 75 year olds and 0.76 (0.73-0.78) in 88 year olds. rCBF in the
      hippocampus, angular and cingular gyri, and frontal association and motor
      cortices was 5-10% lower in the 75 and 88 year olds than in the middle-aged
      subjects (P < 0.05). The annual reduction in rCBF was 0.10% between the ages of
      40 and 75 years and 0.13% between the ages of 75 and 88 years. The reduction in
      rCBF in the hippocampus rose from 0.14% between the ages of 40 and 75 years to
      0.33% between the ages of 75 and 88 years. The mean rCBF in all 33 individuals
      showed no sex-related differences.

PMID- 11453046
TI  - Detection of atherosclerosis using a novel positron-sensitive probe and 18
      fluorodeoxyglucose (FDG).
AB  - Inflammation contributes to atherosclerotic plaque remodeling, enlargement and
      rupture. Non-invasive imaging of coronary artery inflammation could help target
      therapy to 'vulnerable' atheromata, but is limited because of small tissue mass
      and arterial motion. Local radiopharmaceutical imaging may overcome some of these
      limitations. We used a positron-sensitive fiberoptic probe, which can distinguish
      positron emissions from annihilation photons, to identify diseased from healthy
      endothelium in an atherosclerotic model. New Zealand White rabbits underwent
      Fogarty-catheter injury of an iliac artery and then were fed a high-fat diet for
      3 weeks. Fasted animals received 90-180 MBq of 18-fluorodeoxyglucose (FDG) 2-4 h
      before sacrifice and harvest of injured and uninjured iliacs. Arteries were
      incised longitudinally and the probe was placed in contact with the arterial
      intima. Multiple measurements were obtained along 1 cm artery segments in 60 s
      intervals, and corrected for 18F decay and background. Measurements were recorded
      over 93 injured and normal artery segments in 11 animals. Mean probe Z-scores
      were 4.8-fold higher (CI 3.4-6.3) over injury atherosclerosis compared with
      uninjured normal iliac artery segments (P<0.001). Gamma counting confirmed that
      injured artery segments accumulated more FDG per gram than did normal segments
      (0.203% x kg injected dose per gram of tissue versus 0.042, P<0.001). Non
      arterial tissue also accumulated FDG avidly, particularly reticuloendothelial
      tissues and blood. Delayed sacrifice, 4 h compared with 2 h after animal FDG
      injection, further reduced blood background counts and improved the signal-to
      noise ratio. Histopathology confirmed that injured iliac artery had significantly
      higher intimal and medial cross-sectional area compared with uninjured artery.
      Injured artery also had significantly higher macrophage and smooth muscle cell
      density. Positron-sensitive probe counts correlated with the intima to media
      ratio (r =0.63, P = 0.03). Our positron-sensitive probe distinguishes
      atherosclerotic from healthy artery in a blood-free field. Intravascular study of
      plaque biology may be feasible using FDG and a positron-sensitive probe.

PMID- 11453047
TI  - Reproducibility of repeated human regional splenic blood flow measurements using
      [15O] water and positron emission tomography.
AB  - The reproducibility of measurement of regional splenic blood flow by dynamic
      positron emission tomography (PET) using [15O]water was evaluated. In 19
      patients, the correlation between the first and second of two serial dynamic
      measurements was significant (P=1.78 x 10(-6); r=0.858). The regression equation
      was y = 1.06x, and the slope of the line described had a 95% confidence interval
      of 0.09. The error apparent between the two measurements was 0.129 (95%
      confidence interval 0.059). The results demonstrated sufficiently good
      reproducibility for measurements of regional splenic blood flow with PET and
      [15O]water to suggest use of this method for serial measurements intended to
      detect change, including drug effects.

PMID- 11453048
TI  - Performance of simultaneous emission-transmission systems for attenuation
      corrected SPEct: a method for validation applied to two camera systems.
AB  - Several commercially available systems for attenuation correction in single
      photon emission computed tomography (SPECT) based on a transmission scan have
      been introduced that vary in performance. A test procedure for attenuation
      correction in SPECT is described and applied to two principally different gamma
      camera systems (the Siemens Multispect 3 triple-headed system [3HS] and the ADAC
      Genesys Vertex double-headed system [2HS]). The test procedure was based on
      geometrically well-defined phantoms. A torso phantom was used to illustrate the
      attenuation correction methods. The test procedure can be used without detailed
      knowledge of or access to the algorithms used for attenuation correction. The
      influence on the transmission measurement of radioactivity in a phantom was
      higher for the 2HS than for the 3HS. The 3HS produced satisfactory attenuation
      maps and corrected emission count rates to a constant value independent of
      phantom density and size. With the 2HS, there was a progressive decrease in the
      correction of emission count rates with increasing phantom density, and about 30%
      lower corrected count rates in the large compared with the small phantom. A
      decrease in measured attenuation coefficients in the vicinity of an emission
      source was demonstrated in large but not small phantoms. A likely explanation is
      erroneous correction of downscatter into the transmission energy window. This
      study demonstrates the need for independent evaluation of systems for attenuation
      correction in SPECT.

PMID- 11453049
TI  - Differentiating between progressive supranuclear palsy and corticobasal
      degeneration by brain perfusion SPET.
AB  - The purpose of this study was to evaluate the usefulness of brain perfusion
      single photon emission computed tomography (SPET) to differentiate between
      progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Twelve
      patients with PSP and 12 with CBD were examined by brain perfusion SPET using
      99Tc(m)-ethyl cysteinate dimer (99Tc(m)-ECD). The regions of interest (ROIs) were
      five cortical regions, the basal ganglia, the thalamus, the cerebellar cortex and
      the brain stem. The mean regional cerebral blood flow (CBF) and the mean
      right/left asymmetry index in each ROI were calculated. The asymmetry index of
      the regional CBF was significantly higher in CBD patients compared with PSP
      patients in all of the cortical regions and in the basal ganglia. The greatest
      differences in asymmetry were in the parietal cortex (P<0.001), high frontal
      cortex (P<0.001), frontal cortex (P<0.005), temporal cortex (P<0.01) and basal
      ganglia (P<0.01). Significant asymmetry was also detected in the occipital cortex
      (P < 0.05). No significant difference in asymmetry was found in the thalamus or
      the cerebellum. There were no significant differences between the two groups in
      any of the regional CBF values. In conclusion, brain perfusion SPET with 99Tc(m)
      ECD is useful in detecting the significantly higher perfusion asymmetry in CBD
      patients compared with PSP patients in all cortical regions and in the basal
      ganglia. SPET may be a useful tool for differentiating between PSP and CBD.

PMID- 11453050
TI  - Analysis of the early blood kinetics of 99mTc-GSA and its verification: new one
      compartment model and regression equation.
AB  - Technetium-99m-galactosyl human serum albumin (99mTc-GSA) is a
      radiopharmaceutical that binds to asialoglycoprotein receptors in the hepatocyte
      membrane; the level of 99mTc-GSA accumulation in the liver correlates well with
      the parameters of hepatic function tests. We hypothesized that the early blood
      kinetics of 99mTc-GSA could be described by a simple one-compartment model
      expressed as an offset + a monoexponential function (y=y0 +Ae(-alpha)t). The aims
      of this study were to assess the validity of this hypothesis using sequentially
      measured blood levels of 99mTc-GSA, which were approximated by a regression
      expression, and to analyse the regression equation. 99mTc-GSA levels were
      measured in blood samples collected from 30 patients with liver disease. From
      sequential changes in radioactivity up to 30 min after injection, a regression
      equation expressed as an offset+ a monoexponential function was calculated and
      evaluated by multiple correlation coefficients and absolute deviations (% error).
      The liver uptake rate 15 min after injection of 99mTc-GSA (liver uptake rate 15,
      UTR 15) was calculated from the regression equation in each case. The respective
      relationships of this parameter to the coefficient [A] and gradient [alpha] were
      evaluated. In all cases, the measured values of radioactivity in blood samples
      could be fitted to an offset + a monoexponential function. The validity of our
      hypothesis was supported by examining regression equations calculated from blood
      99mTc-GSA levels. Analysis of the regression equations suggested a potential for
      a new index of hepatic functional reserve.

PMID- 11453051
TI  - Value of FDG PET in patients with fever of unknown origin.
AB  - Fever of unknown origin (FUO) is a diagnostic challenge, because the cause of
      such fever may be manifold. Studies on the use of positron emission tomography
      (PET) using 18F-fluorodeoxyglucose (18F-FDG), for the diagnosis of inflammation
      in patients with osteomyelitis or HIV have been promising and suggest its use in
      patients with FUO. In this study, we used FDG PET in 16 patients with FUO in whom
      conventional diagnostics had not been conclusive. In 12 patients, (75%) non
      physiological accumulations of FDG were found which led to the final diagnosis in
      11 patients (69%). FDG PET was negative in four patients (25%). Two of these
      patients had rheumatic fever, while in the other two patients the origin of fever
      could not be detected within 3 months after PET by any other laboratory or
      imaging means. These findings point to the high sensitivity of FDG whole-body PET
      for the detection of morphologically assessable foci as an origin of FUO.
      Moreover, they suggest a high negative predictive value of FDG PET in the setting
      of FUO, since in no patient with a negative FDG PET could a morphological origin
      of the fever be determined. In conclusion, FDG whole-body PET appears to be a
      promising diagnostic tool in patients with FUO, in whom conventional diagnostics
      had been unsuccessful.

PMID- 11453052
TI  - The evaluation of sacroiliitis using 99mTc-nanocolloid and 99mTc-MDP
      scintigraphy.
AB  - The role of imaging studies in the evaluation of patients with sacroiliitis is
      controversial. We aimed to evaluate the role of nanocolloid and bone scintigraphy
      in patients with sacroiliitis and to investigate the clinical relevance of
      imaging findings. Thirty-two patients with clinically sacroiliac disease (nine
      females, 23 males, aged 22-47 years) underwent scintigraphic and radiographic
      examinations and all imaging studies were performed within 2 weeks. Twenty-five
      subjects were also included as a control group (10 females, 15 males, aged 20-51
      years) for quantitative analysis of the bone scan. The quantitative analysis was
      done by using regions of interest drawn over the right and left sacroiliac (SI)
      joint and sacrum (S) and SI/S ratios were calculated. Abnormal uptake was defined
      as an uptake higher than the mean +/- 2 SD of the control SI/S values. Bone
      scintigraphy was performed using a three-phase technique and single photon
      emission computed tomography (SPECT). Nanocolloid scintigraphy (NS) was performed
      1 h later, after administration of 370 MBq 99mTc-nanocolloid, and evaluated
      visually. Each of the scintigraphic examinations was performed on separate days
      within the same week. Sensitivity values were 25%, 47%, 69% and 97%, and
      specificity values were 80%, 90%, 95% and 90% in quantitative bone scanning
      (QBS), 99mTc-NS, planar and SPECT bone imaging, respectively, when the clinical
      findings were considered as the 'gold standard'. Our results showed that bone
      SPECT scanning was more sensitive than planar imaging, but planar imaging was the
      most specific method. SPECT was also the most associated technique with clinical
      findings. 99mTc-NS was neither specific nor sensitive enough in the detection of
      sacroiliitis although it could be helpful for the confirmation of inflammation.

PMID- 11453053
TI  - Relevance of 99mTc-MIBI rest uptake, ejection fraction and location of
      contractile abnormality in predicting myocardial recovery after
      revascularization.
AB  - The aim of this study was to analyse the influence of rest technetium-99m-methoxy
      isobutyl-isonitrile (99mTc-MIBI) uptake, left ventricular ejection fraction (EF)
      and dysfunctional location in the prediction of myocardial viability. Rest 99mTc
      MIBI single photon emission computed tomography (SPECT) was analysed in 82
      patients (59+/-9 years, 70 men, 12 women) with one or more segments showing
      severe hypokinesia, akinesia or dyskinesia who had undergone coronary
      revascularization. Before and within 3-6 months after the revascularization,
      gated blood pool scintigraphy was performed. In the post-revascularization
      control, contractile recovery was observed in 48.7% (155/318) of the segments
      with severe hypokinesia, akinesia or dyskinesia. Significant increases in
      sensitivity (53%, 72% and 91%, P<0.0001) and negative predictive value (62%, 68%
      and 79%, P = 0.01) were observed with decreasing rest uptake 99mTc-MIBI levels of
      50%, 40% and 30%, respectively. The decrease in specificity was also significant
      (67%, 53% and 32%, P<0.0001). The negative predictive value was higher than the
      positive predictive value mainly in patients with EF < or = 0.35 and with
      anterior dysfunction. In logistic regression analysis, uptake levels and EF were
      independent variables that influenced sensitivity and specificity. The negative
      predictive value was influenced by EF and the positive predictive value only by
      dysfunctional location. This study suggests that the negative predictive value of
      99mTc-MIBI SPECT is higher than the positive predictive value, mainly in patients
      with EF < or = 0.35, and that the rest uptake level, EF and dysfunctional
      location are factors that must be considered when results of 99mTc-MIBI SPECT are
      analysed.

PMID- 11453054
TI  - 99Tc(m)-tetrofosmin scintimammography for detecting breast cancer: a comparative
      study with 99Tc(m)-MIBI.
AB  - Scintimammography using 99Tc(m)-MIBI (99Tc(m)-sestamibi) has demonstrated
      promising results in the detection of breast cancer. Recently scintimammography
      using 99Tc(m)-tetrofosmin has been suggested as a better diagnostic tool and a
      more convenient agent to use in this condition. In this study we compared both
      agents in 35 consecutive women with abnormal mammographic or physical findings.
      Thirty-four of them underwent MIBI scan, followed by tetrofosmin scan 2 days
      later (performed on all 35 women). Within 2 weeks, a pathological diagnosis was
      obtained either by needle or open biopsy. In both scans the uptake ratio between
      the lesion and the background uptake was calculated. Twenty patients who
      underwent tetrofosmin scan and 19 patients with MIBI scan had malignant breast
      tumours, while 15 women had benign lesions. The sensitivity, specificity,
      positive and negative predictive values and total accuracy of the MIBI scan were
      89.4%, 80%, 85%, 85.7% and 85.3%, respectively; almost identical values were
      obtained with tetrofosmin (90%, 80%, 85.6%, 85.7% and 85.7%, respectively). The
      uptake ratios in the MIBI and tetrofosmin scans were 1.68 +/- 0.52 and 1.7 +/-
      0.47, respectively. No differences were found between the two scintimammographies
      in all the parameters examined. In conclusion, MIBI and tetrofosmin breast scans
      are accurate and equally efficient for the detection of breast malignancies.

PMID- 11453055
TI  - First pass evaluation of blood velocity in the pulmonary artery.
AB  - Studying the kinetics of blood flow in the pulmonary artery using non-invasive
      techniques may be an important tool in assessing the prognosis of lung diseases.
      The aim of this study was to ascertain dynamic parameters of pulmonary blood
      flow, particularly the velocity of a small bolus of a radioactive tracer after
      intravenous injection. Since the shape and distribution pattern of the bolus
      changes substantially from frame to frame, common image processing techniques for
      motion detection or other techniques, such as accumulation of subtracted images,
      segmentation and spectral analysis with temporal/spatial filtering, are unable to
      properly evaluate the motion of the bolus. However, the passage of the bolus from
      the arm to the lungs was visualized with good contrast through acquisition of a
      first pass sequence of scintigraphic images. The wave form of the bolus becomes
      increasingly complex as it progresses towards the pulmonary artery. In the
      proposed method the time-activity curves for each pixel are displayed. It is
      assumed that the peaks of the maximum counts in these curves correlate with the
      time after injection that the bolus takes to cross each pixel (bolus head). The
      bolus head contains information on time, space and activity, and allows the
      velocity of the studied fluid to be calculated. We demonstrated a mean velocity
      through the pulmonary artery trunk in resting patients of approximately 11 cm/s,
      with a mean residence time of 0.5 s.

PMID- 11453056
TI  - In vivo imaging of neurotransmission: a new era for nuclear neuroimaging.

PMID- 11453057
TI  - Imaging of the dopaminergic system in parkinsonism with SPET.
AB  - Parkinsonism is a feature of various neurodegenerative diseases. Since it is well
      known that the dopaminergic system plays a major role in parkinsonism, numerous
      reports have focused on the assessment of the dopaminergic system in vivo. While
      the use of positron emission tomography (PET) for routine application is still
      hampered by its limited availability, single photon emission tomography (SPET)
      has been shown to deliver comparable results to PET in clinical settings. In
      recent years SPET investigations of the dopamine transporter and of the dopamine
      D2-like receptors have provided valuable information about the pre- and
      postsynaptic dopaminergic system in parkinsonism. This article briefly reviews
      the literature dealing with SPET imaging in parkinsonism and specifically
      addresses the ligands used, the methodology applied, and the current major
      clinical applications.

PMID- 11453058
TI  - Probing targets for antipsychotic drug action with PET and SPET receptor imaging.
AB  - The use of in vivo receptor imaging by positron emission tomography (PET) and
      single photon emission tomography (SPET) has permitted exploration of targets for
      antipsychotic drug action in living patients. Early PET and SPET studies focused
      on striatal D2 dopamine receptors. There is broad agreement that unwanted
      extrapyramidal (parkinsonian) side effects of antipsychotic drugs result from
      high striatal dopamine D2/D3 receptor blockade by these drugs. The dopamine
      hypothesis of antipsychotic drug action suggests that clinical response is
      directly related to the level of striatal D2/D3 receptor occupancy of
      antipsychotic drugs. This may be true for classical antipsychotic drugs, but
      recent evidence suggests that novel, atypical antipsychotic drugs produce
      efficacy in association with modest and transient striatal D2/D3 receptor
      occupancy levels. Furthermore, atypical antipsychotic drugs appear to show
      preferential occupancy of limbic cortical dopamine D2 receptors. Cortical
      dopamine D2/D2-like receptors may be a common site of action for all
      antipsychotic drugs. Data from receptor challenge paradigms has highlighted the
      need to explore the neurotransmitter systems involved in regulating or
      stabilising dopamine transmission, either via dopamine autoreceptors or non
      dopaminergic pathways. These may be promising targets for drug development. In
      vivo PET and SPET imaging has produced unique data contributing to the design of
      better, less toxic drugs for schizophrenia.

PMID- 11453059
TI  - Nuclear medicine in the preoperative evaluation of epilepsy.
AB  - The clinical usefulness of nuclear medicine in the preoperative evaluation of
      epilepsy is highlighted with regard to non-lesional temporal lobe epilepsy,
      extratemporal epilepsy, bitemporal interictal epileptiform discharges (IEDs) and
      in dual pathology and cortical dysgenesis. Ictal single photon emission computed
      tomography (SPECT) shows good sensitivities in the correct lateralization of an
      electroencephalogram-defined epileptic focus in lesional and, to a lesser extent,
      non-lesional epilepsy. Positron emission tomography (PET) using 18F
      fluorodeoxyglucose or 11C-flumazenil gives a good detection rate of the seizure
      onset zone in non-lesional cases and extratemporal epilepsy. The investigation of
      patients with bitemporal IEDs can confirm the existence of bitemporal seizure
      onset. For patients with a dual pathology or cortical dysgenesis nuclear medicine
      offers the opportunity to delineate the existence or extension of abnormalities
      possibly responsible for the seizure disorder.

PMID- 11453060
TI  - LeukoScan protocol.

PMID- 11453061
TI  - Hyperaemic limb vascular volume and Parkin's limb blood flow tests.

PMID- 11453062
TI  - ATP-dependent interaction of yeast U5 snRNA loop 1 with the 5' splice site.
AB  - Pre-messenger RNA splicing is a two-step process by which introns are removed and
      exons joined together. In yeast, the U5 snRNA loop 1 interacts with the 5' exon
      before the first step of splicing and with the 5' and 3' exons before the second
      step. In vitro studies revealed that yeast U5 loop 1 is not required for the
      first step of splicing but is essential for holding the 5' and 3' exons for
      ligation during the second step. It is critical, therefore, that loop 1 contacts
      the 5' exon before the first step of splicing to hold this exon following
      cleavage from the pre-mRNA. At present it is not known how U5 loop 1 is
      positioned on the 5' exon prior to the first step of splicing. To address this
      question, we have used site-specific photoactivated crosslinking in yeast
      spliceosomes to investigate the interaction of U5 loop 1 with the pre-mRNA prior
      to the first step of splicing. We have found that the highly conserved uridines
      in loop 1 make ATP-dependent contacts with an approximately 8-nt region at the 5'
      splice site that includes the invariant GU. These interactions are dependent on
      functional U2 and U6 snRNAs. Our results support a model where U5 snRNA loop 1
      interacts with the 5' exon in two steps during its targeting to the 5' splice
      site.

PMID- 11453063
TI  - Specific sequence elements in the 5' untranslated regions of rbcL and atpB gene
      mRNas stabilize transcripts in the chloroplast of Chlamydomonas reinhardtii.
AB  - Using a series of point mutations in chimeric reporter gene constructs consisting
      of the 5' regions of the Chlamydomonas chloroplast rbcL or atpB genes fused 5' to
      the coding sequence of the bacterial uidA (GUS) gene, RNA-stabilizing sequence
      elements were identified in vivo in the 5' untranslated regions (5' UTRs) of
      transcripts of the chloroplast genes rbcL and atpB in Chlamydomonas reinhardtii.
      In chimeric rbcL 5' UTR:GUS transcripts, replacement of single nucleotides in the
      10-nt sequence 5'-AUUUCCGGAC-3', extending from positions +38 to +47 relative to
      the transcripts' 5' terminus, shortened transcript longevity and led to a
      reduction in transcript abundance of more than 95%. A similar mutational analysis
      of atpB 5' UTR:GUS transcripts showed that the 12-nt atpB 5' UTR sequence 5'
      AUAAGCGUUAGU-3', extending from position +31 to position +42, is important for
      transcript stability and transcript accumulation in the chloroplast of
      Chlamydomonas. We discuss how the 5' UTR sequence elements, which are predicted
      to be part of RNA secondary structures, might function in RNA stabilization.

PMID- 11453064
TI  - Position and sequence requirements for poly(A) length regulation by the poly(A)
      limiting element.
AB  - The poly(A)-limiting element (PLE) is a cis-acting sequence that acts to limit
      poly(A) tail length on pre-mRNA to <20 nt. Functional PLEs are present in a
      number of genes, underscoring the generality of this control mechanism. The
      current study sought to define further the position requirements for poly(A)
      length regulation and the core sequence that comprises a PLE. Increasing the
      spacing between the PLE and the upstream 3' splice site or between the PLE and
      the downstream AAUAAA had no effect on poly(A) length control. However, moving
      the PLE from the terminal exon to either an upstream exon or intron eliminated
      poly(A) length control. Poly(A) length control was further evaluated using a
      battery of constructs in which the PLE was maintained in the terminal exon, but
      where upstream introns were either deleted, modified, or replaced with a
      polypyrimidine tract. Poly(A) length control was retained in all cases,
      indicating that the key feature is the presence of the PLE in the terminal exon.
      A battery of mutations demonstrated the importance of the 5' pyrimidine-rich
      portion of the element. Finally, UV crosslinking experiments identified an
      approximately 62-kDa protein in Hela nuclear extract that binds to a wild-type 23
      nt PLE RNA oligonucleotides but not to a mutated nonfunctional form of the
      element.

PMID- 11453065
TI  - A minihelix-loop RNA acts as a trans-aminoacylation catalyst.
AB  - We previously reported a bifunctional ribozyme that catalyzes self-aminoacylation
      and subsequent acyl-transfer to a tRNA. The ribozyme selectively recognizes a
      biotinyl-glutamine substrate, and charges the tRNA molecule in trans.
      Structurally, there are two catalytic domains, referred to as glutamine
      recognition (QR) and acyl-transferase (ATRib). We report here the essential
      catalytic core of the QR domain as determined by extensive biochemical probing,
      mutation, and structural minimization. The minimal core of the QR domain is a 29
      nt helix-loop RNA, which is also able to glutaminylate ATRib in trans. Its amino
      acid binding site is embedded in an 11-nt cluster that is adjacent to the loop
      that interacts with the ATRib domain. Our study shows that a minihelix-loop RNA
      can act as a trans-aminoacylation catalyst, which lends support for the critical
      role of minihelix-loops in the early evolution of the aminoacylation system.

PMID- 11453066
TI  - A new nomenclature of group I introns in ribosomal DNA.

PMID- 11453067
TI  - Analysis of codon:anticodon interactions within the ribosome provides new
      insights into codon reading and the genetic code structure.
AB  - Although the decoding rules have been largely elucidated, the physical-chemical
      reasons for the "correctness" of codon:anticodon duplexes have never been clear.
      In this work, on the basis of the available data, we propose that the correct
      codon:anticodon duplexes are those whose formation and interaction with the
      ribosomal decoding center are not accompanied by uncompensated losses of hydrogen
      and ionic bonds. Other factors such as proofreading, base-base stacking and
      aminoacyl-tRNA concentration contribute to the efficiency and accuracy of
      aminoacyl-tRNA selection, and certainly these factors are important; but we
      suggest that analyses of hydrogen and ionic bonding alone provides a robust first
      order approximation of decoding accuracy. Thus our model can simplify predictions
      about decoding accuracy and error. The model can be refined with data, but is
      already powerful enough to explain all of the available data on decoding
      accuracy. Here we predict which duplexes should be considered correct, which
      duplexes are responsible for virtually all misreading, and we suggest an
      evolutionary scheme that gave rise to the mixed boxes of the genetic code.

PMID- 11453068
TI  - Purine N7 groups that are crucial to the interaction of Escherichia coli rnase P
      RNA with tRNA.
AB  - We have detected by nucleotide analog interference mapping (NAIM) purine N7
      functional groups in Escherichia coli RNase P RNA that are important for tRNA
      binding under moderate salt conditions (0.1 M Mg2+, 0.1 M NH4+). The majority of
      identified positions represent highly or universally conserved nucleotides. Our
      assay system allowed us, for the first time, to identify c7-deaza interference
      effects at two G residues (G292, G306). Several c7-deazaadenine interference
      effects (A62, A65, A136, A249, A334, A351) have also been identified in other
      studies performed at very different salt concentrations, either selecting for
      substrate binding in the presence of 0.025 M Ca2+ and 1 M NH4+ or self-cleavage
      of a ptRNA-RNase P RNA conjugate in the presence of 3 M NH4+ or Na+. This
      indicates that these N7 functional groups play a key role in the structural
      organization of ribozyme-substrate and -product complexes. We further observed
      that a c7-deaza modification at A76 of tRNA interferes with tRNA binding to and
      ptRNA processing by E. coli RNase P RNA. This finding combined with the strong c7
      deaza interference at G292 of RNase P RNA supports a model in which substrate and
      product binding to E. coli RNase P RNA involves the formation of intermolecular
      base triples (A258-G292-C75 and G291-G259-A76).

PMID- 11453069
TI  - Altered discrimination of start codons and initiator tRNAs by mutant initiation
      factor 3.
AB  - IF3 is essential for ensuring the fidelity of the initiation step of translation
      in bacterial cells. Mutations at residues R99 and R131 in the C-terminal domain
      of the factor have previously been shown to increase initiation from the non
      canonical GUA codon. Here we show that these mutant forms of IF3 fail to
      discriminate against initiation from many different non-AUG codons. They also
      enhance the activity of mutant tRNAs carrying changes in the three consecutive G
      C pairs that are conserved in the anticodon stem of initiator tRNAs. In addition,
      the IF3 mutants stimulate initiations from leaderless mRNAs and from internal
      initiation codons, in the absence of any SD-anti-SD interaction. These results
      indicate that IF3 ensures the accuracy of initiation by inspecting both the codon
      anticodon pairing and unique features of the initiator tRNA as well as
      suppressing initiation from other potential start sites within the mRNA.

PMID- 11453070
TI  - The packaging signal of influenza viral RNA molecules.
AB  - The packaging signal present in influenza viral RNA molecules is shown not to
      constitute a separate structural element, but to reside within the 5'-bulged
      promoter structure, as caused by the central unpaired residue A10 in its 5'
      branch. Upon insertion of two uridine residues in the 3' branch opposite A10, the
      minus-strand viral RNA (vRNA) promoter is converted into a 3'-bulged structure,
      whereas the plus-strand cRNA promoter instead adopts the 5'-bulged conformation.
      In this promoter variant it is exclusively the cRNA that is found packaged in the
      progeny virions. Upon insertion of only a single uridine nucleotide opposite
      5'A10, the two debulged structures of the vRNA and cRNA promoters are rendered
      identical, and both vRNA and cRNA molecules are packaged indiscriminately, in a
      1:1 ratio, but at lower rates. We propose that the binding interactions of viral
      polymerase with either of the two differently bulged vRNA and cRNA promoter
      structures result in two different conformations of the enzyme protein. Only the
      5' bulged RNA-associated polymerase conformation appears to be recognized for
      nuclear export, which depends on nuclear matrix protein M1 and nonstructural
      protein NS2. And the respective wild-type vRNP- or insertion mutant cRNP complex
      is observed to enter the cytoplasm and hence is included in the viral
      encapsidation process, which takes place at the plasma membrane.

PMID- 11453071
TI  - A second function for pseudouridine synthases: A point mutant of RluD unable to
      form pseudouridines 1911, 1915, and 1917 in Escherichia coli 23S ribosomal RNA
      restores normal growth to an RluD-minus strain.
AB  - This laboratory previously showed that truncation of the gene for RluD, the
      Escherichia coli pseudouridine synthase responsible for synthesis of 23S rRNA
      pseudouridines 1911, 1915, and 1917, blocks pseudouridine formation and inhibits
      growth. We now show that RluD mutants at the essential aspartate 139 allow these
      two functions of RluD to be separated. In vitro, RluD with aspartate 139 replaced
      by threonine or asparagine is completely inactive. In vivo, the growth defect
      could be completely restored by transformation of an RluD-inactive strain with
      plasmids carrying genes for RluD with aspartate 139 replaced by threonine or
      asparagine. Pseudouridine sequencing of the 23S rRNA from these transformed
      strains demonstrated the lack of these pseudouridines. Pseudoreversion, which has
      previously been shown to restore growth without pseudouridine formation by
      mutation at a distant position on the chromosome, was not responsible because
      transformation with empty vector under identical conditions did not alter the
      growth rate.

PMID- 11453072
TI  - Determinants on tmRNA for initiating efficient and precise trans-translation:
      some mutations upstream of the tag-encoding sequence of Escherichia coli tmRNA
      shift the initiation point of trans-translation in vitro.
AB  - tmRNA facilitates a novel translation, trans-translation, in which a ribosome can
      switch between translation of a truncated mRNA and the tmRNA's tag sequence. The
      mechanism underlying resumption of translation at a definite position is not
      known. In the present study, the effects of mutations around the initiation point
      of the tag-encoding sequence of Escherichia coli tmRNA on the efficiency and the
      frame of tag translation were assessed by measuring the incorporations of several
      amino acids into in vitro poly (U)-dependent tag-peptide synthesis. One
      nucleotide insertions within the tag-encoding region did not shift the frame of
      tag translation. Any 1-nt deletion within the span of -5 to -1, but not at -6,
      made the frame of tag translation heterologous. Positions at which a single base
      substitution caused a decrease of trans-translation efficiency were concentrated
      within the span of -4 to -2. In particular, an A-4 to C-4 mutation seriously
      damaged the trans-translation, although this mutant retained normal
      aminoacylation and ribosome-binding abilities. A possible stem and loop structure
      around this region was not required for transtranslation. It was concluded that
      the tag translation requires the primary sequence encompassing -6 to +11, in
      which the central 3 nt, A-4, G-3, and U-2, play an essential role. It was also
      found that several base substitutions within the span of -6 to -1 extensively
      shifted the tag-initiation point by -1.

PMID- 11453073
TI  - New cholesterol guidelines: better, but harder to follow.

PMID- 11453074
TI  - A young woman with fever, headache, and lymphadenopathy.

PMID- 11453075
TI  - How should hyperuricemia be treated in a patient with allopurinol
      hypersensitivity?

PMID- 11453076
TI  - Does salmeterol increase mortality in patients with COPD?

PMID- 11453077
TI  - A 47-year-old man with a sore throat.

PMID- 11453078
TI  - Use of cholinesterase inhibitors for treatment of Alzheimer disease.
AB  - The four cholinesterase inhibitors now available for treatment of Alzheimer
      disease (AD) may be most beneficial, especially in the long run, if started early
      in the course of the disease. This paper reviews the efficacy, pharmacokinetics,
      metabolism, side effects, dosage, and precautions for the use of these agents,
      which may produce modest improvements in cognition, behavior, and the ability to
      perform activities of daily living.

PMID- 11453079
TI  - Using the new cholesterol guidelines in everyday practice.
AB  - The third Adult Treatment Panel guidelines from the National Cholesterol
      Education Program, released in May 2001, depart from previous guidelines in
      several ways. As in previous guidelines, treatment and treatment goals are based
      not only on lipid levels but also on the patient's risk status. The method for
      calculating risk, however, has been refined considerably. Patients are classified
      in the highest-risk group if they have any of these disorders: known coronary
      artery disease, diabetes mellitus, peripheral vascular disease, abdominal aortic
      aneurysm, carotid artery disease, or a 10-year risk of a coronary event of more
      than 20% (as determined by use of a scoring method).

PMID- 11453080
TI  - Patient information. Cholesterol: what you need to know.
AB  - Cholesterol is a fat-like substance that is in our blood. Our bodies naturally
      produce some cholesterol. The other portion comes from animal products such as
      meat, eggs, butter, cheese, and whole milk. Foods from plants do no contain
      cholesterol. When you have a high level of cholesterol in your blood, it builds
      up in the walls of your arteries. Over time, this buildup causes the arteries to
      narrow and become hard, which slows down blood flow to the heart. This reduced
      blood flow can cause chest pain when you exercise, walk, or exert yourself in any
      way. If the blood flow is completely blocked off to a portion of your heart, a
      heart attack can occur.

PMID- 11453081
TI  - Mitochondrial cytopathy in adults: what we know so far.
AB  - Mitochondrial cytopathies are a diverse group of inherited and acquired disorders
      that result in inadequate energy production. They can be caused by inheritable
      genetic mutations, acquired somatic mutations, exposure to toxins (including some
      prescription medications), and the aging process itself. In addition, a number of
      well-described diseases can decrease mitochondrial energy production; these
      include hyperthyroidism, hypothyroidism, and hyperlipidemia.

PMID- 11453082
TI  - Maximizing response to erythropoietin in treating HIV-associated anemia.
AB  - Anemia, a common complication of HIV infection, is associated with morbidity and
      shortened survival. HIV-associated anemia can often be corrected with
      erythropoietin (EPO) therapy, which is safer than blood transfusion. Because the
      response to erythropoietin may be impaired by a number of treatable factors, all
      HIV patients with anemia should undergo careful evaluation for these factors.
      This article reviews evaluation and treatment strategies to maximize response to
      EPO and thus limit the need for blood transfusion.

PMID- 11453083
TI  - Recognizing and treating social anxiety disorder.
AB  - Social anxiety disorder is the third most common psychiatric disorder in the
      United States. Patients strive to avoid stress-inducing situations, or they may
      endure them with marked psychological distress and physical reactions, including
      sweating and tachycardia. Social anxiety disorder can be diagnosed by a careful
      history and can be treated successfully with medications or psychosocial
      interventions.

PMID- 11453084
TI  - Trends in hospital medicine: hospitalist advantages revealed.
AB  - Although research on hospitalists is in its infancy, this model appears to reduce
      health care costs while providing care of at least equal quality to that provided
      by primary care physicians. This paper reviews recent reports.

PMID- 11453085
TI  - Polymorphism of uridine monophosphate kinase: population study in Japanese and
      phenotyping in bloodstains.
AB  - The polymorphism of UMPK was investigated in 677 unrelated Japanese individuals.
      The allele frequencies were estimated to be UMPK*1 = 0.9594 and UMPK*2 = 0.0406.
      Our sample was devoid of the UMPK*3 allele. Phenotyping was also possible from
      bloodstains stored at 37 degrees C for up to 1 week, at room temperature for up
      to 4 weeks and at 4 degrees C over 10 weeks. The UMPK system can be a useful
      supplement for the mediocolegal grouping of bloodstains.

PMID- 11453086
TI  - Transferrin gene frequencies in Cadiz (southern Spain).
AB  - The genetic polymorphism of transferrin (Tf) was studied in a sample of 385
      healthy unrelated subjects of both sexes resident in the province of Cadiz
      (southern Spain). Isoelectric focusing was carried out in polyacrylamide gels,
      followed by staining with Coomassie Blue R250. The gene frequencies obtained were
      as follows: Tf C1, 0.7922; Tf C2, 0.1883; Tf C3, 0.0195.

PMID- 11453087
TI  - Immunochemical demonstration of plasminogen phenotypes using electroblotting.
AB  - The polymorphism of plasminogen (PLG) was analysed by isoelectric focusing on
      polyacrylamide gels, followed by electroblotting. For analysis, neuraminidase
      pretreated sera were used. In a random sample of 500 unrelated individuals from
      east Westphalia 8 phenotypes were observed. The allele frequencies were: PLG*1
      (A), 0.708; PLG*2 (B), 0.274; PLG*3 (A3), 0.013; PLG*V, 0.005. The family data
      (300 mother-child pairs) confirmed the hypothesis of autosomal codominant
      inheritance. PLG phenotypes could be determined in 1-year-old bloodstains (cotton
      and glass) that had been stored at +4 degrees C and -20 degrees C. The PLG
      phenotypes could clearly be demonstrated in sera diluted 1:4. The phenotype 1 (A)
      could still be detected in dilutions of 1:6. The theoretical exclusion rate was
      calculated to be 22.6%.

PMID- 11453088
TI  - A TLC screening program for 170 commonly used pesticides using the corrected Rf
      value (Rf(c) value).
AB  - This article reports TLC data (corrected Rf values; Rf(c) values) of 170 commonly
      used pesticides which are regularly encountered in toxicological analysis. Silica
      gel was used as the stationary phase and three binary systems were chosen as
      solvents.

PMID- 11453089
TI  - Chlamydia and sudden infant death syndrome. A study of 166 SIDS and 30 control
      cases.
AB  - Chlamydia inclusions could be demonstrated by an immunofluorescence assay in
      formalin-fixed lung sections in 32 of 166 cases (19.4%) of Sudden Infant Death
      Syndrome (SIDS) and in the lungs of only 1 of 30 infants with a known cause of
      death (3.3%). The difference is statistically significant (P = 0.04). Chlamydia
      trachomatis is an agent of pneumonia in 1-4 month-old infants who have acquired
      the disease from an infected cervix during birth, but other chlamydia species are
      also capable of causing pneumonia. The lung sections of the 32 chlamydia positive
      SIDS cases did not show typical histological signs of pneumonia. Even though
      chlamydia inclusions were detected in the lungs of 32 SIDS cases a causal
      relation between chlamydia infection and SIDS could not be demonstrated.

PMID- 11453090
TI  - BamHI polymorphism of locus D2S44 in a West German population as revealed by VNTR
      probe YNH24.
AB  - BamHI polymorphism at the VNTR locus D2S44 was investigated, concentrating on
      band frequencies, mutation rate and confirmation of Mendelian inheritance. In
      this series 39 restriction fragments showing frequencies less than 10% could
      clearly be distinguished. No mutations could be observed and the Mendelian
      character of inheritance is beyond reasonable doubt.

PMID- 11453091
TI  - Morphine in postmortem blood: its importance for the diagnosis of deaths
      associated with opiate addiction.
AB  - This article describes an analytical method for the determination of morphine,
      the active metabolite of heroin, in post-mortem blood by HPLC with
      electrochemical detection. An extraction technique allowing the determination of
      free and total morphine (free morphine + morphine glucuronide) was used. Blood
      morphine levels in postmortem cases are reported and the ratio of free to total
      morphine was measured in 52 cases obtained at autopsy. The importance of this
      ratio is discussed in relation to the circumstances of the death.

PMID- 11453092
TI  - Toxicological detection of pholcodine and its metabolites in urine and hair using
      radio immunoassay, fluorescence polarisation immunoassay, enzyme immunoassay, and
      gas chromatography-mass spectrometry.
AB  - Pholcodine (3-O-(2'-morpholinoethyl)-morphine) is used in many countries as an
      antitussive without analgesic or addictive properties. It is of forensic
      relevance that pholcodine interferes with opiate immunoassays. In this paper a
      gas chromatographic-mass spectrometric (GC-MS) procedure for the precise and
      sensitive detection of pholcodine and its metabolites in urine and hair, after
      acid hydrolysis, extraction and acetylation, is presented. Furthermore, detection
      of pholcodine using radio immunoassay (RIA), fluorescence polarisation
      immunoassay (FPIA) and enzyme immunoassay (EIA) for opiates is described. Using
      GC-MS, unmodified pholcodine could be detected in urine samples 4-7 weeks after
      ingestion of a single therapeutic dose of 50mg of pholcodine, the
      desmorpholinohydroxy metabolite for 1-2 weeks and the other metabolites (nor-,
      nordesmorpholinohydroxy-, hydroxy-, oxo- and noroxo-pholcodine) only during the
      first few hours. Morphine could also be detected in urine samples for the first
      few days. It was however mainly formed artificially during acid hydrolysis and
      only in trace amounts by metabolism. All the immunoassays tested gave positive
      results in urine samples during the first week taking the cut-off values
      recommended by the manufacturer into consideration. If values between the cut-off
      and the detection limit were taken into consideration, RIA and FPIA gave positive
      results for 2-4 weeks and EIA up to 2 weeks. Pholcodine could also be detected by
      RIA and GC-MS in samples of head hair clipped 10 weeks after ingestion of 50mg
      and in daily shaved samples of beard hair over a period of three weeks after
      ingestion of three doses of 60mg. It can be concluded that the widely used
      immunoassays for opiates show positive results in urine and hair samples for a
      long time after ingestion of the non-opioid pholcodine and that these results can
      be confirmed by the GC-MS procedure described in this paper.

PMID- 11453093
TI  - A fatal accident on the football field.
AB  - A 21-year old centre forward died after a collision with the opposing goalkeeper
      during a football match. The centre forward fell to the ground on his back and
      the goalkeeper fell on top of him, his knee hitting the centre forward hard in
      the chest and neck. There was no obvious foul and the referee did not award a
      penalty. The ambulance arrived too late to save the player's life. The
      medicolegal autopsy revealed a severe contusion of the larynx and rupture of
      thyroid cartilage, which resulted in hemorrhage and caused death by suffocation.

PMID- 11453094
TI  - An interesting case of arterial trauma after craniocerebral injury.
AB  - A 63-year-old drunken man fell and hit his head on the ground. Apart from
      symptoms of alcoholisation no signs of severe injuries were found. The man died 2
      1/2 days after the accident. The autopsy revealed a huge fracture system in the
      right parietal region. A branch of the medial cerebral artery was stretched
      between the cortex and one of the fracture lines, passing through a tear in the
      dura. Characteristics of this case were that no larger hemorrhage was found and
      the artery which was torn from the cortex showed no lesions. The case also
      indicates the immense relative movements between skull and brain which occur
      during such trauma.

PMID- 11453095
TI  - An unusual case of sudden death in an alcohol addict.
AB  - The sudden and unexpected death of a 40-year-old female alcohol addict is
      described. At the autopsy recent rib fractures were found. The extremity of one
      fractured rib had caused a massive haemorrhage by erosion of a coronary artery.

PMID- 11453096
TI  - Fatal air embolism during female autoerotic practice.
AB  - Air embolism has been described in pregnant women and is a classic cause of death
      during attempted abortion by syringing. Death was caused by the introduction of
      an amount of air sufficient to cause a substantial air lock in the heart,
      pulmonary trunk or arteries. If the surface of the placenta has been stripped by
      the syringe, venous spaces are opened and air can pass into the circulation.
      Orogenital sex with vaginal insufflation can also cause air embolism during
      pregnancy. We report a case of air embolism in a 40-year-old non-pregnant woman
      subsequent to vaginal insertion of a foreign body (carrot) for an autoerotic
      purpose. The mechanism is roughly similar to syringing, the foreign body acting
      like a piston to displace a sufficient amount of air. In the present case, the
      endometrium stripping was probably due to the presence of an intrauterine device.
      As such risks may often be encountered and as, to our knowledge, no similar case
      has previously been reported, we may speculate if such air embolisms are
      underdiagnosed or dissimulated by the partners when questioned by the medical
      rescue teams.

PMID- 11453097
TI  - Species identification of blood and bloodstains by high-performance liquid
      chromatography.
AB  - A reverse-phase high-performance liquid chromatographic method for species
      identification of blood and bloodstains is described. The method employs a 300 A
      pore SynChropak RP-4 column and ternary solvents (acetonitrile-trifluoroacetic
      acid-water) and can not only identify a species by its characteristic
      chromatogram, but also simultaneously demonstrates that it is of blood origin by
      the existence of the heme peak. Deformations in chromatographic profiles obtained
      with older bloodstains were observed, but the retention times of heme and the
      major peaks showed only minor changes. The species could be identified from
      bloodstains at least 3 months old and the present method has the advantage of
      simplicity, speed and sensitivity in the practice of forensic science.

PMID- 11453098
TI  - Physiological background of the change point in VO2 and the slow component of
      oxygen uptake kinetics.
AB  - It is generally believed that oxygen uptake during incremental exercise--until
      VO2max, increases linearly with power output (see eg. Astrand & Rodahl, 1986). On
      the other hand, it is well established that the oxygen uptake reaches a steady
      state only during a low power output exercise, but during a high power output
      exercise, performed above the lactate threshold (LT), the oxygen uptake shows a
      continuous increase until the end of the exercise. This effect has been called
      the slow component of VO2 kinetics (Whipp & Wasserman, 1972). The presence of a
      slow component in VO2 kinetics implies that during an incremental exercise test,
      after the LT has been exceeded, the VO2 to power output relationship has to
      become curvilinear. Indeed, it has recently been shown that during the
      incremental exercise, the exceeding of the power output, at which blood lactate
      begins to accumulate (LT), causes a non-proportional increase in VO2 (Zoladz et
      al. 1995) which indicates a drop in muscle mechanical efficiency. The power
      output at which VO2 starts to rise non-proportionally to the power output has
      been called "the change point in VO2" (Zoladz et al. 1998). In this paper, the
      significance of the factors most likely involved in the physiological mechanism
      responsible for the change point in oxygen uptake (CP-VO2) and for the slow
      component of VO2 kinetics, including: increase of activation of additional muscle
      groups, intensification of the respiratory muscle activity, recruitment of type
      II muscle fibres, increase of muscle temperature, increase of the basal metabolic
      rate, lactate and hydrogen ion accumulation, proton leak through the inner
      mitochondrial membrane, slipping of the ATP synthase and a decrease in the
      cytosolic phosphorylation potential, are discussed. Finally, an original own
      model describing the sequence of events leading to the non-proportional increase
      of oxygen cost of work at a high exercise intensity is presented.

PMID- 11453099
TI  - Delay in oral mucosal ulcer healing by aspirin is linked to the disturbances in
      p38 mitogen-activated protein kinase activation.
AB  - BACKGROUND: Among the early manifestations of oral mucosal impairment by
      nonsteroidal anti-inflammatory drugs is the delay in soft oral tissue repair
      brought about by the amplification of apoptotic events. In this study, we
      investigated the effect of a specific inhibitor of p38 mitogen-activated protein
      kinase (p38 MAPK), SB 203580, on the rate of buccal mucosal ulcer healing and the
      apoptotic processes in rats subjected to intragastric administration of aspirin.
      METHODS: Groups of rats with experimentally induced buccal mucosal ulcers were
      administered twice daily for 10 days with SB 203580 (5, 10, and 20 mg/kg) or
      vehicle followed 30 min later by concomitant administration (twice daily for 10
      days) of aspirin at 20 mg/kg. The animals were killed at different periods of
      treatment and their mucosal tissue subjected to macroscopic assessment of ulcer
      healing rate, measurement of soluble tumor necrosis factor-alpha (TNF-alpha), and
      the assay of epithelial cell apoptosis. RESULTS: In the control group the ulcer
      healed by the tenth day and the rate of healing was not affected by SB 203580
      administration, whereas a 54.8% reduction in the ulcer area was attained in the
      presence of aspirin administration. Moreover, by the tenth day, the delay in
      ulcer healing caused by aspirin was manifested in a 5.6-fold higher rate of
      apoptosis and a 5.2-fold higher level of soluble TNF-alpha. Treatment with SB
      203580 produced dose-dependent reduction (59.5-74.8%) in aspirin-induced increase
      in the mucosal level of soluble TNF-alpha, evoked 53.2-69.7% decrease in the rate
      of epithelial cell apoptosis, and led to a marked reversal (51.8-73.9%) in
      aspirin-induced delay in ulcer healing. CONCLUSIONS: The results of our findings
      link the delay in buccal mucosal ulcer healing caused by aspirin ingestion to the
      disturbances in the p38 MAPK activation.

PMID- 11453100
TI  - Role of p38 mitogen-activated protein kinase in the healing of gastric ulcers in
      rats.
AB  - p38 belongs to the mitogen-activated protein kinase family and plays a crucial
      role in cellular responses to both cytokines and various stresses. We
      investigated the role of p38 in the healing of experimental gastric ulcers.
      Gastric ulcers were induced by submucosal injection of acetic acid solution into
      male rats. Western blotting and a kinase assay examined the p38 activity and
      phosphorylation state in ulcerated tisue. After orally administering FR167653
      (p38 kinase inhibitor) for 3 to 14 days, the production level of cytokines and
      the protein-level expression of cyclooxygenase and inducible nitric oxide
      synthase were examined by enzyme-linked immunosorbent assay and Western blotting.
      Only in fibroblasts and macrophages/monocytes in ulcerated tissue, p38 was found
      to be phosphorylated with an elevated kinase activity level. FR 167653 inhibited
      the activity of p38, yet had no effect on its phosphorylation state. The drug
      significantly impaired ulcer healing (without affecting acid secretion) and
      angiogenesis in the ulcer base. The production of interleukin-1beta and tumor
      necrosis factor-alpha were significantly reduced after FR167653 treatment. In
      addition the expression of cyclooxygenase-2 and inducible nitric oxide synthase
      proteins increased PGE2 generation and NOx secretion in the ulcerated stomach
      were suppressed by FR167653. From these findings, we conclude that p38, activated
      by gastric ulceration, might play some role in the healing of gastic ulcers in
      rats.

PMID- 11453101
TI  - The effect of nitric oxide donors and L-arginine on the gastric electrolyte
      barrier.
AB  - The potential difference across the stomach wall (PD) is determined by the
      gastric mucosal barrier. The decrease in the PD evoked by "the barrier breakers",
      e.g. aspirin, ethanol or bile acids is believed as a sensitive index of the
      mucosal damage. The effect of glyceryl trinitrate (GTN), isosorbide dinitrate
      (IDN) and molsidomine (MOL)--all exogenous donors of nitric oxide (NO), as well
      as L-arginine (L-ARG), which is a substrate for NO-synthase and Nomega-nitro-L
      arginine (L-NNA), a non-selective NO synthase inhibitor on the gastric
      electrolyte barrier were studied against the gastric damage induced by ethanol.
      All NO donors given intragastrically alone caused only moderate, not significant
      changes in the PD and failed to affect the mucosal barrier, while L-NNA slightly
      decreased the PD. The NO donors and L-arginine applied as pretreatment prior to
      ethanol resulted in diminishing of its damaging action that was similar for all
      these drugs, while L-NNA intensified both the injury and the drop in the PD
      values caused by ethanol. In summary, our results showed the protective effect of
      endogenous nitric oxide from L-ARG and that originating from GTN, MOL and IDN on
      the gastric electrolyte barrier, supporting involvement of nitric oxide in the
      mechanism of gastric protection in the stomach.

PMID- 11453102
TI  - Pancreatic damage and regeneration in the course of ischemia-reperfusion induced
      pancreatitis in rats.
AB  - The objective of this study was to assess the biochemical and histological signs
      of pancreatic damage development and pancreatic recovery in the course of
      ischemia-reperfusion induced pancreatitis. Acute pancreatitis was induced in rats
      by limitation of pancreatic blood flow (PBF) in inferior splenic artery for 30
      min using microvascular clips, followed by reperfusion. Rats were sacrificed at
      the time: 1 h, 12 h, 24 h, and 2, 3, 5, 7, 10, 14, 21 and 28 days after ischemia.
      PBF was measured using laser Doppler flowmeter. Plasma amylase, interleukin 1beta
      (IL-1beta) and interleukin 10 (IL-10) concentration, pancreatic DNA synthesis, as
      well as, morphological features of pancreatic damage were examined. Ischemia with
      reperfusion caused acute necrotizing pancreatitis followed by pancreatic
      regeneration. After removal of microvascular clips, PBF was reduced and the
      maximal fall of PBF was observed 24 h after ischemia, then PBF grew reaching the
      control value at 28th day. Plasma amylase activity was increased between 12th h
      and 3rd day with maximum at 24 h after ischemia. Also plasma IL-1beta and IL-10
      were elevated with maximal value at the first and second day after ischemia,
      respectively. DNA synthesis was maximally reduced at the first day (by 70%) and
      from second day the reversion of this tendency was observed with full restoration
      of pancreatic DNA synthesis within four weeks. Morphological features of
      pancreatic tissue showed necrosis, strongly pronounced edema and leukocyte
      infiltration. Maximal intensity of morphological signs of pancreatic damage was
      observed between first and second day of reperfusion. During pancreatic
      regeneration between second and tenth day after ischemia the temporary appearance
      of chronic pancreatitis-like features such as fibrosis, acinar cell loss,
      formation of tubular complexes and dilatation of ducts was observed. The
      regeneration was completed within four weeks after pancreatitis development. We
      conclude that partial and temporary pancreatic ischemia followed by reperfusion
      causes acute necrotizing pancreatitis with subsequent regeneration within four
      weeks. Pancreatic repair after necrotizing pancreatitis is connected with the
      increase in plasma IL-10 concentration and transitory formation of tubular
      complexes.

PMID- 11453103
TI  - Cerebral angiogenesis after subarachnoid hemorrhage (SAH) and endothelin receptor
      blockage with BQ-123 antagonist in rats.
AB  - The aim of the study was to determine the effect of chronic vasospasm after SAH
      on angiogenesis and the effect of endothelin-1, the main causative factor in
      vasospasm, on this process. Male Wistar rats, 220-250 g, were examined. Seven
      days after cannulation of the cisterna magna (CM), a 100 microl dose of non
      heparinized blood was administered to induce SAH. Sham SAH (aSAH) was induced by
      intracisternal injection of 100 microl of artificial cerebrospinal fluid.
      Endothelin receptor antagonist BQ-123 in a dose of 40 nmol in 50 microl of
      cerebrospinal fluid was given three times: 20 min. before SAH and aSAH, 60 min
      and 24 hours after SAH and aSAH. The same pattern of BQ-123 administration was
      used in the nonSAH group. The brains were removed 48 hours later for histological
      evaluation. Vascular surface density was measured in cerebral hemisphere sections
      (at the level of the dorsal part of the hippocampus) and brain stem sections (1/2
      of the pons). An increase in angiogenesis was observed after SAH, compared to
      control values. The administration of BQ-123, a specific endothelin receptor
      blocker inhibits angiogenesis in cerebral hemispheres after SAH.

PMID- 11453104
TI  - Role of 5-hydroxytryptamine1B receptors and 5-hydroxytryptamine uptake inhibition
      in the cocaine-evoked discriminative stimulus effects in rats.
AB  - Mesolimbic dopamine pathways play a critical role in the behavioural effects of
      cocaine in rodents. Nonetheless, research has also demonstrated involvement of 5
      hydroxytryptamine (5-HT; serotonin) transmission in these effects. The present
      study investigated the ability of selective 5-HT1B receptor ligands and a 5-HT
      reuptake inhibitor to substitute for or to alter (enhance or antagonise) the
      discriminative stimulus effects of cocaine. Male Wistar rats were trained to
      discriminate cocaine (10 mg/kg, i.p.) from saline (i.p.) in a two-choice, water
      reinforced fixed ratio (FR) 20 drug discrimination paradigm. In substitution
      tests, the selective 5-HT1B receptor agonist 3-(1,2,5,6-tetrahydro-4-pyridyl)-5
      propoxypyrrolo[3,2-b]pyridine (CP 94253; 2.5-5 mg/kg, i.p.) and the 5-HT reuptake
      inhibitor fluoxetine (5-10 mg/kg, i.p.) elicited ca. 40 and 0% drug-lever
      responding, respectively. In combination experiments, CP 94253 (2.5-5 mg/kg)
      given with submaximal doses of cocaine (0.3-2.5 mg/kg) produced a leftward shift
      in the cocaine dose-response curve; pretreatment with CP 94253 (5 mg/kg) prior to
      a dose of cocaine (2.5 mg/kg) which elicited lower than 40% drug-lever
      responding, caused full substitution. Fluoxetine (5 and 10 mg/kg) given in
      combination with a submaximal dose of cocaine (2.5 mg/kg) produced a 100% drug
      lever responding. Pretreatment with the 5-HT1B receptor antagonists N-[4-methoxy
      3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)
      1,1'-biphenyl-4 carboxamide (GR 127935; 0.5-5 mg/kg, s.c.) and 3-(3
      dimethylamino)-propyl)-4-hydroxy-N-[4-(4-pyridinyl)-phenyl]benzamide (GR 55562; 1
      mg/kg, s.c.) failed to modulate the dose-effect curve for cocaine (0.6-5 mg/kg).
      On the other hand, GR 127935 (5 mg/kg) and GR 55562 (1 mg/kg) significantly
      attenuated the enhancement of cocaine discrimination evoked by a combination of
      CP 94253 (5 mg/kg) or fluoxetine (5 mg/kg) and cocaine (2.5 mg/kg). These results
      indicate that 5-HT1B receptors are not directly involved in the cocaine-induced
      discriminative stimuli in rats. On the other hand, they indicate that
      pharmacological stimulation of 5-HT receptors--that also seem to be a target for
      fluoxetine-mediated increase in 5-HT neurotransmission--can enhance the overall
      effects of cocaine.

PMID- 11453105
TI  - Different receptor subtypes are involved in the serotonin-induced modulation of
      epileptiform activity in rat frontal cortex in vitro.
AB  - The frontal cortex is innervated by serotonergic terminals from the raphe nuclei
      and it expresses diverse 5-HT receptor subtypes. We investigated the effects of 5
      HT and different 5-HT receptor subtype-selective agonists on spontaneous
      discharges which had developed in rat cortical slices perfused with a Mg2+-free
      medium and the GABA(A) receptor antagonist picrotoxin. The frequency of
      synchronous discharges, recorded extracellularly in superficial layers (II/III)
      of the frontal cortex, was dose-dependently enhanced by 5-HT (2.5-40 microM).
      That excitatory effect was blocked by the 5-HT2 receptor selective antagonist
      ketanserin. The 5-HT2A/2C receptor-selective agonist DOI and the 5-HT4 receptor
      agonist zacopride also increased the frequency of spontaneous discharges. In the
      presence of ketanserin, 5-HT decreased the discharge rate; a similar effect was
      observed when the 5-HT1A receptor agonist 8-OH-DPAT or the 5-HT1B receptor
      agonist CGS-12066B was applied. The 5-HT3 receptor agonist m-CPBG was
      ineffective. In conclusion, 5-HT produces multiple effects on epileptiform
      activity in the frontal cortex via activation of various 5-HT receptor subtypes.
      The excitatory action of 5-HT, which predominates, is mediated mainly by 5-HT2
      receptors. The inhibitory effects can be attributed to activation of 5-HT1A and 5
      HT1B receptors.

PMID- 11453106
TI  - Fever induced oxidative stress: the effect on thyroid status and the 5'
      monodeiodinase activity, protective role of selenium and vitamin E.
AB  - The thyroid hormones metabolism is considerably altered in many pathological
      processes including fever. Experiments performed on rabbits (n=62) showed that
      increase in the rectal temperature by 1 degrees C (after turpentine oil sc
      injections) decreased 5'-monodeiodinase activity, the enzyme responsible for
      deiodination of thyroxine to the most active thyroid hormone 3,3',5
      triiodothyronine (T3), in the liver by 25% and in the kidney by 20%.
      Triiodothyronines concentration in serum decreased during fever from 1.57+/-0.12
      to 0.52+/-0.02 nmolT3/l and from 0.17+/-0.01 to 0.07+/-0.02 nmol rT3/l. The
      increase in the body temperature intensified lipid peroxidation processes
      (malondialdehyde level increased from 1.2 times in kidney, and 1.4 times in the
      liver homogenates to 1.6 times in serum). The antioxidants (vitamin E and
      selenium) supplementation decreased lipid peroxidation processes during fever and
      partly restored the 5'-monodeiodinase activity. The present study confirmed our
      previous observations in vitro that lipid peroxidation (free radical formation)
      influences the 5'-monodeiodinase activity in tissues and alters the thyroid
      hormones metabolism.

PMID- 11453107
TI  - Vitamin C decreases intracellular calcium level in human lymphoid cells.
AB  - Human lymphocytes have low levels of many antioxidant enzymes however they are
      know to concentrate vitamin C. Cell injury, including oxidative stress effects,
      is associated with calcium influx so the influence of vitamin C on the
      maintenance of calcium levels in leukocytes was studied. Incubation of Molt-3
      human lymphoblastoid cells with physiologically relevant concentrations of
      vitamin C and the calcium ionophore A23187 reversed the calcium influx and
      increased nuclear protein level associated with the ionophore alone. It is
      concluded that intracellular vitamin C can inhibit calcium influx into leukocytes
      so helping to minimise cell damage.

PMID- 11453108
TI  - The evaluation of murine pleural lavage fluid cellular composition in
      experimental hemorrhagic shock with special regard to mast cells morphometry.
AB  - In the course of a hemorrhagic shock, pathological changes occur, which result in
      intensifying the insufficiency of various vital organs. It can also lead to the
      development of the multiorgan dysfunction syndrome (MODS) that is the cause of
      high posthemorrhagic mortality. As a result of the ischemia in the lung there
      appear proinflammatory factors that mobilize and activate mast cells, inducing
      degranulation in them. The aim of the study was the analysis of cellular
      composition and cytomorphometric evaluation of mast cells present in the lavage
      fluid from the pleural cavity of rats in a sham operated group and in the group
      presenting hemorrhagic shock. The results revealed an increase of the total cell
      count in the lavage fluid from the pleural cavity. In the cytological smears a
      statistically significant accumulation of inflammatory cells was present,
      especially neutrophils. The increase in mast cells and eosinophils number was not
      statistically significant. There was not a change in the morphometric parameters
      of mast cells except the circularity index. A decline of the circularity index
      indirectly may suggest the degranulation of mast cells, which reflects an
      inflammatory process in the lungs.

PMID- 11453109
TI  - Aryl hydrocarbon receptor (AhR)-linked inhibition of luteal cell progesterone
      secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin treated cells.
AB  - In this study, we tested firstly, the hypothesis that decrease of progesterone
      secretion by luteal cells under the influence of 2,3,7,8-tetrachlorodibezo-p
      dioxin (TCDD) is due to influence on specific enzymatic steps in the biosynthetic
      pathway of steroidogenesis and secondly, involvement of aryl hydrocarbon receptor
      (AhR) or estradiol receptor (ER) in this process. Luteal cells isolated from
      mature porcine corpora lutea were cultured with 25-hydroxycholesterole (25-OH) or
      pregnenolone (P5) as a substrate. Additionally aminoglutethimide, the inhibitor
      of P540scc or trilostane the inhibitor of 3 beta-HSD was added to basal and
      stimulated cells. The synergistic action of TCDD with aminoglutethimide in
      decreasing of progesterone secretion was observed. In pregnenolone treated cells
      1.6 fold decrease of progesterone secretion was observed that in both TCDD alone
      and together with trilostane treated cells. In the second part of experiments to
      show the involvement of AhR and ER in TCDD action on progesterone secretion alpha
      naphtophlavone, the AhR blockers and 4-hydroxytamoxifen (4-OH-TMX), the
      inhibitor of ER were used. alpha-naphtophlavone, the inhibitory effect of TCDD
      while 4-OH-TMX had no effect on TCDD-treated cells. These experiments suggest
      TCDD decreased progesterone secretion by luteal cells by reduction of the
      activity of mitochondrial enzymes, which converts cholesterol into pregnenolone.
      Moreover points to AhR dependent but not ER-dependent mechanisms in TCDD action
      in luteal cells.

PMID- 11453110
TI  - A single corticosterone pretreatment inhibits the hypothalamic-pituitary-adrenal
      responses to adrenergic and cholinergic stimulation.
AB  - The purpose of the present study was to determine whether an increased plasma
      corticosterone or dexamethasone levels induced by a single corticosterone or
      dexamethasone injection to conscious rats affects the hypothalamic-pituitary
      adrenocortical (HPA) activity induced by adrenergic and cholinergic agonists.
      Male Wistar rats were pretreated subcutaneously (s.c.) with a single dose of
      dexamethasone (5 mg/kg) or corticosterone (25 mg/kg) 24 or 48 h before
      intraperitoneal (i.p.) administration of adrenergic agonists: phenylephrine, an
      alpha1-adrenergic receptor agonist, clenbuterol, a beta2-adrenergic agonist and
      noradrenaline acting predominantly on alpha1-adrenoreceptors, and cholinergic
      agonists: carbachol, a predominant muscarinic receptor agonist and nicotine, a
      nicotinic receptor agonist. Dexamethasone profoundly decreased the resting ACTH
      levels in control rats and given 24 h before each of the stimulatory agonist
      abolished the adrenergic- and cholinergic agonists-induced ACTH and
      corticosterone responses. Pretreatment with corticosterone of control rats did
      not substantially alter the resting plasma ACTH and serum corticosterone levels
      measured 24 and 48 h later. A single pretreatment with corticosterone abolished
      or powerfully inhibited, perhaps by a feedback mechanism, the ACTH and
      corticosterone responses induced 24 and 48 h later by all adrenergic and
      cholinergic agonists used in this study. These results indicate that prolonged
      administration of corticosterone is not necessary to induce almost complete
      suppression of the HPA responsiveness to adrenergic or cholinergic stimulation.
      Chronic treatment with corticosteroids to achieve glucocorticoid receptors
      desensitization does not seem to be required.

PMID- 11453111
TI  - Expression of bone associated macromolecules by gingival and periodontal ligament
      fibroblasts.
AB  - The expression of hard tissue associated proteins may be used to identify
      periodontal fibroblasts with the capability to facilitate periodontal
      regeneration. The aim of this study was to describe, by immunohistochemistry, the
      distribution of osteocalcin, osteopontin, bone sialoprotein and bone morphogenic
      proteins-2 and -4 (BMP-2 and BMP-4) within the human periodontium. Furthermore,
      the expression of mRNA for the above proteins and alkaline phosphatase by
      gingival and periodontal ligament fibroblasts in vitro was also assessed by
      reverse transcriptase polymerase chain reaction (RT-PCR). Localization of
      osteopontin, osteocalcin, BMP-2 and BM P-4 within sections of human periodontal
      structures was stronger in the periodontal ligament compared to the gingiva. Bone
      sialoprotein was not detected in either of the soft tissues but, along with
      osteopontin and osteocalcin, it was localized in the cementum and bone. In vitro,
      both the gingival and periodontal ligament fibroblasts expressed mRNA for
      alkaline phosphatase, BMP-2, BMP-4 and osteopontin. Although there were no
      differences in the expression of alkaline phosphatase and BMP-4 mRNA between the
      two cell types, we noted significantly higher mRNA levels of osteopontin in the
      periodontal ligament and BM P-2 in the gingival fibroblasts. Osteocalcin and bone
      sialoprotein mRNA expression was only noted in the cultured periodontal ligament
      fibroblasts. From these results, it can be concluded that distinct differences
      exist between the two fibroblast populations in terms of the localization and
      mRNA expression of the majority of the hard tissue associated proteins.
      Furthermore, the elevated in vitro mRNA expression for osteocalcin, osteopontin
      and bone sialoprotein may be used to identify cells with the potential to
      facilitate hard tissue formation and hence periodontal regeneration.

PMID- 11453112
TI  - Prostaglandin E2 secretion from gingival fibroblasts treated with interleukin
      1beta: effects of lipid extracts from Porphyromonas gingivalis or calculus.
AB  - Complex lipids of Porphyromonas gingivalis have been identified in lipid extracts
      from calculus-contaminated root surfaces and in diseased gingival tissues.
      However, little is known about the biological effects of these complex lipids on
      host cells. The purpose of this study was to evaluate the effects of P.
      gingivalis or calculus lipids on prostaglandin secretion from gingival
      fibroblasts. Lipids were extracted from paired subgingival plaque and teeth
      samples, and calculus-contaminated root surfaces before and after scaling and
      root planing, in order to determine the relevant levels of lipid extracts for the
      treatment of gingival fibroblasts in culture. Primary cultures of gingival
      fibroblasts were exposed to lipid extracts from either P. gingivalis or
      calculus/teeth for a period of 7 days. Control and lipid-treated cultures were
      exposed to human recombinant interleukin-1beta for 48 h and prostaglandin
      secretion from interleukin-1beta-treated fibroblasts was compared with control
      and lipid-treated fibroblasts without interleukin-1beta treatment. These
      experiments demonstrated that P. gingivalis lipids or calculus-tooth lipids
      potentiate interleukin-1beta-mediated prostaglandin secretory responses from
      gingival fibroblasts. Additionally, P. gingivalis or calculus-tooth lipid
      extracts were readily taken up by gingival fibroblasts as measured by bacterial
      fatty acid recovery in lipid extracts of cultured fibroblasts. These results
      indicate that bacterial lipid penetration into gingival tissues in combination
      with a chronic inflammatory response may substantially potentiate prostaglandin
      secretion from gingival fibroblasts, thereby promoting tissue destructive
      processes associated with adult periodontitis.

PMID- 11453113
TI  - Induction of collagenase-2 (matrix metalloproteinase-8) gene expression by
      interleukin-1beta in human gingival fibroblasts.
AB  - Collagenase-2 (matrix metalloproteinase-8 or MMP-8) is synthesized mainly by
      polymorphonuclear neutrophils and plays a crucial role in inflammatory
      periodontal tissue destruction. We tested the effect of interleukin(IL)-1beta, a
      proinflammatory cytokine, on collagenase-2 gene expression in cultured human
      gingival fibroblasts and also compared this effect with IL-1beta-induced changes
      in collagenase-1 and -3 gene expression. By a combination of reverse
      transcription-polymerase chain reaction and Southern analysis, IL-1beta was found
      to dose-dependently induce gene expression for collagenase-1, -2, and -3 in
      gingival fibroblasts. Although collagenase-2 mRNA was the least abundant among
      the three collagenase mRNAs tested in the cultured fibroblast system, addition of
      1 ng/ml IL-1beta significantly increased collagenase-2 gene transcription within
      6 h, and maximal stimulation was maintained for 12 to 48 h. Significant mRNA
      induction was observed with as little as 0.1 ng/ml IL-1beta. IL-1beta was also
      found to increase the stability of collagenase-2 mRNAs after transcription arrest
      was induced by an RNA polymerase inhibitor. Stimulation of collagenase-2 mRNA
      expression by IL-1beta was prevented by pretreatment with cycloheximide, an
      inhibitor of protein synthesis. These results indicate that IL-1beta increased
      mRNA expression for collagenases including collagenase-2 in gingival fibroblasts.
      The findings also suggest that enhancement of collagenase-2 mRNA expression by IL
      1beta involves both protein synthesis and suppression of mRNA degradation.

PMID- 11453114
TI  - Elevated mRNA expression for supervillin and vascular endothelial growth factor
      in human neutrophils stimulated with lipopolysaccharide from Porphyromonas
      gingivalis.
AB  - Differential gene expression was examined in human neutrophils stimulated with
      lipopolysaccharide from Porphyromonas gingivalis (P. gingivalis-LPS) using RNA
      fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). LPS
      from Escherichia coli (E. coli-LPS) was used as control. More than 200
      differently expressed transcripts were found in 8 subjects showing differential
      regulation at the transcriptional level. Densitometric analyses revealed that 42
      100 genes were upregulated, while 53-116 genes were downregulated by P.
      gingivalis-LPS compared with E. coli-LPS. The results of sequencing
      identification showed the presence of supervillin (SVIL) and vascular endothelial
      growth factor (VEGF) genes in the clones which were upregulated by P. gingivalis
      LPS. Consequently, semiquantitative analyses proved that the level of mRNA for
      SVIL and VEGF were significantly higher in P. gingivalis-LPS-stimulated
      neutrophils than in other bacterial (E. coli, Actinobacillus
      actinomycetemcomitans, Prevotella intermedia) LPS- or synthetic lipid A
      stimulated neutrophils. Our findings suggest that an elevated mRNA expression for
      SVIL could be associated with impaired function of neutrophils when stimulated by
      P. gingivalis-LPS. Further, the VEGF mRNA over-expression might be related to the
      pathogenesis of P. gingivalis-associated periodontitis. The RAP-PCR technique
      used in this study enabled us to identify a number of P. gingivalis-LPS regulated
      genes which hitherto have not been reported.

PMID- 11453115
TI  - Crevicular fluid elastase levels in relation to periodontitis and metabolic
      control of diabetes.
AB  - The purpose of this study was to investigate the associations between gingival
      crevicular fluid (GCF) elastase levels, clinical measures of periodontal status,
      and metabolic control of diabetes in insulin dependent (type 1) diabetes (IDDM)
      and non-insulin dependent (type 2) diabetes (NIDDM) patients. Sixty patients were
      recruited from the Diabetes Center at the University of California in San
      Francisco. Thirty subjects were type 1 diabetics and 30 subjects were type 2
      diabetics. Metabolic control was evaluated by glycosylatted hemoglobin (HbA1c)
      levels. Demographic information was obtained using a structured interview with
      the subjects. Clinical measurements and GCF samples were taken from the mesio
      buccal surfaces of 2 premolars and 2 molars from the most diseased sextant. GCF
      elastase was determined by measurement of p-Nitroanalide resulting from
      hydrolysis of elastase specific peptide. Crevicular fluid elastase levels were
      significantly correlated with gingival index, bleeding index, probing depth and
      attachment level in both type 1 and type 2 diabetes groups (0.01 <p < 0.001).
      HbA1c levels were not correlated with clinical measurements and GCF elastase. The
      results suggest that GCF elastase. age and smoking are risk indicators for
      periodontitis in patients with diabetes mellitus, and periodontal status is not
      associated with the duration and metabolic control of diabetes.

PMID- 11453116
TI  - Effect of aging on bone formation induced by recombinant human bone morphogenetic
      protein-2 combined with fibrous collagen membranes at subperiosteal sites.
AB  - This study was designed to examine the effect of aging on bone formation induced
      by recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with a
      fibrous collagen membrane (FCM). Implantation was done subperiosteally in
      bilateral palatal grooves in 34 male Wistar rats divided into three age groups: a
      10-week-old group (10w group), a 30-week-old group (30w group) and a 70-week-old
      group (70w group). RhBMP-2-combined FCMs were implanted on the left palatal
      grooves as BMP-implanted sites (BMP site), while rhBMP-2 was not implanted on the
      right palatal grooves as control sites. The rats were sacrificed 6 weeks after
      implantation, and histometric evaluations were performed. New bone formation was
      observed in every site of each age group and the new bone was almost completely
      continuous with the original bone. The new bone volume (NBV) of the BMP site was
      significantly higher than that of the control site in each age group. The NBV of
      both the control and BMP sites were highest in the 10w group and lowest in the
      70w group. The disparity of NBV between the control and BMP sites, which
      indicated the response to implanted BMP excluding the effect of skeletal growth
      and surgical stimulation, did not significantly differ among the age groups.
      These results indicate that rhBMP-2-combined FCM has the ability to induce new
      bone formation continuous with original bone even in senescent rats. Furthermore,
      it appeared that, in the case of palatal subperiosteal implantation, the
      responsiveness to implanted BMP was independent of age, although the total volume
      of newly formed bone declined with aging.

PMID- 11453117
TI  - Genetic polymorphism of the tumor necrosis factor (TNF)-alpha promoter region in
      families with localized early-onset periodontitis.
AB  - Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine that is
      able to induce tissue destruction and bone resorption. A G-to-A polymorphism at
      the -308 position of the TNF-alpha promoter region was suggested to influence TNF
      alpha production. We had previously shown that monocytes of patients with
      localized early-onset periodontitis (EOP) secrete high levels of TNF-alpha
      compared to matched controls. The aim of the present study was to investigate the
      possible link between the -308 polymorphism in the TNF-alpha gene and EOP.
      Genomic DNA was extracted from the blood of 64 individuals from 11 nuclear
      families with EOP. The TNF-alpha polymorphism at -308 was assessed using allele
      specific polymerase chain reaction. 77% of the tested adolescents were found to
      have the G/G genotype, and 23% had the A/G genotype. In the diseased subjects,
      81% were with G/G genotype and 19% with A/G genotype. The healthy children had
      74% G/G genotype, while 26% had A/G genotype. The differences between the disease
      group and the healthy group were not statistically significant. In summary, the
      present results could not demonstrate any link between EOP and genetic
      polymorphism in the -308 position of the TNF-alpha promoter.

PMID- 11453118
TI  - Phase 1 evaluation of a local delivery device releasing silver ions in
      periodontal pockets: safety, pharmacokinetics and bioavailability.
AB  - A new local delivery device (LDD) capable of releasing silver in periodontal
      pockets has been developed and tested pre-clinically. Silver has potent
      antimicrobial effects on Gram-negative periodontal pathogens with a mean in vitro
      minimum bactericidal concentration (MBC) < or =0.5 microg/ml. This phase 1 study
      assessed the safety, pharmacokinetics and bioavailability of silver ions
      delivered intracrevicularly with a resorbable LDD (PocketGuard) in a group of 9
      volunteers affected with periodontitis. In each subject, a PLGA/PEG LDD loaded
      with 12% silver nitrate (w/w) was inserted in each of 4 selected pockets > or =5
      mm. Serum, gingival fluid and subgingival plaque samples were evaluated before
      and at various time points after LDD placement for 21 days. At each time point,
      the concentration of silver in gingival crevicular fluid (GCF) was quantified
      with an Inductively Coupled Plasma-Mass Spectrometer. Subgingival plaque samples
      were processed for evaluation of total anaerobic and aerobic counts (CFU/ml). The
      maximum mean silver concentration in GCF was 1,493 +/- 709 microg/ml (range 589
      2,245). It decayed exponentially with a half-life of 7.1 +/- 6.1 days (2.7-20.4).
      Average silver concentrations in excess of 10 microg/ml were detected in each
      patient for 14 days after LDD placement with the average concentration for all
      patients in excess of 25 microg/mL at day 21. Total anaerobic counts decreased an
      average of 1.7 +/- 1.9 x 10(6) CFU/ml (p= 0.0078) from baseline to day 7,
      indicating that the silver was biologically active. A mild increase in cervical
      root discoloration was observed at day 21:0.25 +/- 0.31 stain index units.
      Discoloration that did not resolve spontaneously could be removed at the end of
      the study with polishing. No systemic effects were observed. It is concluded that
      local silver concentrations above the MBC in serum were maintained for at least
      21 days. A specific microbiologic effect was also observed.

PMID- 11453119
TI  - Characterization of cellular infiltrate, detection of chemokine receptor CCR5 and
      interleukin-8 and RANTES chemokines in adult periodontitis.
AB  - Leukocyte migration is essential for immune surveillance of tissues by focusing
      immune cells to sites of antigenic challenge. The control of leukocyte migration
      depends on the combined actions of adhesion molecules and a vast array of
      chemokines and their receptors. The purpose of the present study was to
      investigate the involvement of Interleukin-8 (IL-8), RANTES, the associated
      infiltrating cells and expression of CCR5 chemokine receptors in periodontitis;
      furthermore, the effect of periodontal therapy on these parameters was evaluated.
      Patients included in the study had moderate to advanced periodontal disease with
      at least 5-6 teeth with probing depth > 6 mm, attachment loss > or =3 mm and
      extensive radiographic bone loss. The inflammatory infiltrate was analyzed by
      immunohistochemistry in gingival biopsies obtained from subjects at the beginning
      of the study and 2 months after periodontal treatment. Gingival crevicular fluid
      (GCF) was collected for 30 seconds using periopaper strips, and chemokines were
      quantified by ELISA. The cellular components of the inflammatory infiltrate
      included B (CD19) and T (CD3, CD4+ and CD8+) lymphocytes and
      monocytes/macrophages (CD11c). CCR5 chemokine receptor expressing cells were
      exclusively found in periodontitis gingiva. IL-8 and RANTES were detected in the
      periodontitis group, obtaining a total amount of 212.5 pg and 42.0 pg,
      respectively. However, IL-8 was also detectable in the GCF of the healthy group
      (total amount of 44.8 pg). Periodontal therapy reduced the cell number in the
      infiltrate and the levels of IL-8 and RANTES, suggesting a relationship between
      these chemokines and periodontal status. We propose that the presence of these
      chemokines and the expression of chemokine receptors may represent a marker of
      lymphocyte subsets with the ability to migrate to inflammatory sites.

PMID- 11453120
TI  - Supernormal left ventricular diastolic function in triathletes.
AB  - We studied the structural and functional heart adaptations of 52 male triathletes
      compared with those of 22 active, nonathletic men, by 2-dimensional Doppler
      echocardiography. Left ventricular diastolic function was evaluated by recording
      transmitral flow velocities. To exclude the influences of preload, left atrial
      pressure, and aortic pressure, left ventricular diastolic function was also
      evaluated by pulsed Doppler tissue imaging. Significant differences in cardiac
      structure and function were observed between the 2 groups. In the triathletes,
      the left ventricular diastolic function was completely normal, despite signs of
      mixed eccentric and concentric left ventricular hypertrophy, and this function
      was better than that in the control group. We measured 2 aspects of the late
      passive diastolic filling period in the triathletes: ASEAC value (the amplitude
      of excursion of the interventricular septal endocardium at the end of left
      ventricular diastole just after atrial contraction); and the time between onset
      of the P wave on the electrocardiographic tracing and onset of systolic septal
      movement on M-mode echocardiography. Pulsed Doppler tissue imaging confirmed
      these results. The E/A ratios (peak early left ventricular diastolic motion
      velocity divided by the peak atrial systolic motion velocity), measured by pulsed
      Doppler tissue imaging, yielded even more evidence for supernormal left
      ventricular diastolic function in the triathletes. Left ventricular relaxation
      and filling properties were measured along the longitudinal and transverse axes
      by pulsed Doppler tissue imaging, which was useful for evaluating left
      ventricular diastolic function. We determined that triathletes may develop
      supernormal left ventricular diastolic function with increased diastolic
      reserves.

PMID- 11453121
TI  - Aneurysm of the left atrial appendage.
AB  - A 43-year-old woman underwent excision of an aneurysm of the left atrial
      appendage, which had been causing cerebrovascular embolic episodes. We attribute
      the aneurysm to congenital dysplasia of the musculi pectinati in the left atrial
      appendage and of the bands of atrial muscle from which they arise. In Appendix I,
      we draw attention to the morphologically similar arrangements of inner and outer
      bands that emanate from a common transverse interatrial band and yield
      morphologically similar medial, descending, and ascending palm-leaf arrangements
      of musculi pectinati. In addition, we observe that the strap-like arrangements of
      musculi in both atria connect the outer band with the para-annular segment of the
      inner band. In Appendix II, we briefly review the literature concerning musculi
      pectinati and related bands.

PMID- 11453122
TI  - Transcatheter coil occlusion of a thoracic arteriovenous fistula in an infant
      with congestive heart failure.
AB  - An 8-week-old baby boy presented at our institution with a continuous murmur and
      congestive heart failure. Echocardiography showed normal cardiac anatomy.
      Catheterization revealed the presence of a large thoracic arteriovenous fistula
      between the descending thoracic aorta and the hemiazygous system, with eventual
      drainage into the azygous vein and the innominate vein. Coil occlusion was
      performed successfully with a Gianturco coil.

PMID- 11453123
TI  - Right pulmonary artery-to-left atrium communication: a rare cause of systemic
      cyanosis.
AB  - Direct communication between the right pulmonary artery and the left atrium is a
      rare congenital vascular malformation. The clinical diagnosis is difficult, and
      preoperative angiography is essential. We treated this anomaly successfully with
      surgery and the use of cardiopulmonary bypass in an 11-year-old boy. Surgery
      provides a complete cure for this anomaly.

PMID- 11453124
TI  - Three new applications of stent technology in a single patient.
AB  - The use of endovascular stents has become widely established in maintaining both
      arterial and venous patency in congenital heart disease. Stent implantation is
      now applied to pulmonary arterial stenoses, coarctation, pulmonary and systemic
      venous obstruction, and obstructed homografts and conduits, in both the pediatric
      and adult populations. The purpose of this report is to describe 3 new
      applications of stent technology: 1) double pulmonary artery stent implantation
      with simultaneous balloon dilation of a previously placed stent; 2) a new
      technique for traversing tight pulmonary arterial corners for stent delivery
      using the "sheath-within-sheath" method; and 3) a new technique for recannulation
      and stent implantation in unilateral femoral venous occlusion.

PMID- 11453125
TI  - The technical aspects of radial artery harvesting.
AB  - We describe our technique for harvesting the radial artery for coronary
      revascularization. Anatomy and preoperative preparation are also presented, as
      well as the history of the radial artery as a bypass conduit, the advantages, and
      some contraindications. We have found that, with proper harvesting, the radial
      artery is an effective means of coronary artery revascularization.

PMID- 11453126
TI  - A biographical sketch of Lewis Dexter.
AB  - Dr. Lewis Dexter was an outstanding cardiovascular physiologist and clinician, a
      respected teacher and scientist, and, most importantly, a fine human being.
      During his life, he brought the cardiac catheter from the laboratory to the
      patient and trained several generations of cardiologists. Dexter's laboratory was
      the first to elucidate the pathophysiologic alterations present in many forms of
      congenital heart disease, including atrial septal defects, patent ductus
      arteriosus, tetralogy of Fallot, ventricular septal defects, and pulmonic
      stenosis. Subsequent work in Dexter's laboratory led to the 1st measurements of
      pulmonary capillary wedge pressure and to the precise calculation of stenotic
      valve areas from hemodynamic parameters measured during cardiac catheterization.
      During a teaching exercise, Dexter demonstrated that exercise with a cardiac
      catheter in the heart was safe and produced clinically important data, by having
      a cardiac catheter inserted in himself. Over the years, many significant
      pathophysiologic studies that explored pulmonary embolism, valvular heart
      disease, right and left ventricular function, and pulmonary hypertension were
      published from Dexter's laboratory. But Lewis Dexter was more than a brilliant
      researcher "Lew" was very close to his fellows and students, whom he considered
      extensions of his family Dexter was a remarkable teacher, a compassionate
      physician, and a scrupulously honest investigator. Dr Lewis Dexter had a major
      impact on modern medicine and was one of the great cardiologists of the 20th
      century.

PMID- 11453127
TI  - A reliable test to detect impending pump failure during long-term support on the
      Novacor N100 Left Ventricular Assist System.
AB  - The Durastudy is a new surveillance protocol to detect impending pump failure in
      Novacor N100 Left Ventricular Assist Systems implanted for the long term. Our
      patient, a 54-year-old man with a history of dilated cardiomyopathy and
      contraindications for heart transplantation, received a Novacor pump in May 1995
      and did not experience sustainable ventricular recovery during the subsequent 3
      years. After more than 3 years of support, symptoms of pump wear were detected in
      this patient, through application of the Durastudy protocol. This enabled us to
      electively exchange the pump at 3.8 years. Our patient remained in New York Heart
      Association functional class I until he died in July 1999 of causes unrelated to
      the pump, after some 1,514 days of support. This, we believe, still constitutes a
      world record.

PMID- 11453128
TI  - Severe rhabdomyolysis associated with the cerivastin-gemfibrozil combination
      therapy: report of a case.
AB  - Cerivastatin is the new 3rd-generation of the synthetic 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, the 1st drugs of choice
      for treating hypercholesterolemia. A potent inhibitor of HMG-CoA reductase, it
      possesses a high affinity for liver tissue and decreases plasma low-density
      lipoprotein cholesterol at microgram doses. Cerivastatin produces reductions in
      low-density lipoprotein cholesterol of 31.3% and 36.1% at doses of 0.3 and 0.4
      mg/day, respectively It is an uncomplicated agent with regard to its
      pharmacokinetic profile, low potential for interaction with other drugs, and
      suitability for use in those with impaired renal function. Most other statins
      have been implicated in causing rhabdomyolysis, either as monotherapy or in
      combination with other agents. We report what to our knowledge is the most
      profound case yet in the literature of rhabdomyolysis in association with
      cerivastatin-gemfibrozil combination therapy, in regard both to the extreme
      elevation in serum creatinine kinase and to the patient's near-paralytic
      weakness.

PMID- 11453129
TI  - Coronary artery bypass grafting nine months after pneumonectomy.
AB  - We performed coronary artery bypass grafting on a 58-year-old man who only 9
      months earlier had undergone right pneumonectomy for bronchial carcinoma.
      Although his preoperative pulmonary function had been poor, coronary artery
      bypass surgery was successful, and the patient was discharged on the 9th
      postoperative day Two years after surgery, he remained in New York Heart
      Association functional class I. We attribute this success to special management
      before, during, and after the operation. On the 32nd postoperative month, this
      patient died of multiple tumor metastases.

PMID- 11453130
TI  - Acute dissecting aneurysm of the ascending thoracic aorta causing obstruction and
      thrombosis of the right pulmonary artery.
AB  - We present the case of a 69-year-old man with a history of hypertension and a
      recent pelvic fracture who presented with acute chest pain, shortness of breath,
      and severe hypotension. The history of recent pelvic fracture and the clinical
      manifestations, including the sudden onset of acute respiratory distress,
      hypotension, and hypoxemia, indicated pulmonary embolism; however, at surgery the
      patient was found to have an acute dissection of the ascending aorta with
      obstruction and thrombosis of the right pulmonary artery. This case emphasizes
      the need to consider such a diagnosis in patients who have unilateral absence of
      perfusion to the right lung.

PMID- 11453131
TI  - Acute type-B aortic dissection in association with isthmic coarctation.

PMID- 11453132
TI  - Cardiac involvement in sarcoidosis.

PMID- 11453133
TI  - Coarctation of the aorta: echocardiographic diagnosis in a child.

PMID- 11453134
TI  - Giant left atrium.

PMID- 11453135
TI  - Extreme annuloaortic dilation of the ascending aorta.

PMID- 11453136
TI  - A novel approach to the prevention of thromboembolism in atrial fibrillation.

PMID- 11453137
TI  - Neurologic complications after deep hypothermic circulatory arrest: types,
      predictors, and timing.
AB  - To determine the nature of neurologic dysfunction after deep hypothermic
      circulatory arrest during aortic arch surgery, we reconsidered the cases of 154
      patients who had undergone aortic arch surgery (either of the ascending or
      transverse aorta, or both) between November 1993 and July 1999. Temporary
      postoperative neurologic dysfunction was seen in 9 patients (5.8%), and another 3
      patients (1.9%) experienced stroke. Patients with temporary neurologic
      dysfunction had no new infarct and were discharged home with no residual
      symptoms. Computed tomographic scans revealed that 2 patients with stroke had
      multiple infarcts in the brainstem, and the 3rd had bilateral border-zone
      infarcts. The patients with brainstem infarcts died on postoperative days 7 and
      15, and the patient with border-zone infarct was discharged home with no symptoms
      3 months after surgery. Univariate analysis revealed that patients with
      neurologic deficits had significantly higher rates of history of hypertension,
      concomitant coronary artery bypass grafting, cardiac ischemia times longer than
      90 minutes, and chronic renal failure. A multivariate logistic regression
      analysis revealed that the significant preoperative variables associated with
      neurologic deficits were a history of hypertension and a cardiac ischemia time
      longer than 90 minutes. Deep hypothermic circulatory arrest is a safe and useful
      technique for protection of the brain during surgery for complex aortic problems.
      In future, some patients at extreme risk for perioperative neurologic
      complications might be offered novel neuroprotective agents, in combination with
      deep hypothermia.

PMID- 11453138
TI  - Impact of double internal thoracic artery grafts on long-term outcomes in
      coronary artery bypass grafting.
AB  - We performed this study to determine if bilateral internal thoracic artery grafts
      provide greater benefit than single internal thoracic artery grafts. Six hundred
      ninety-four consecutive patients who received 2 coronary grafts in a single
      operation during 1983-1989 were given 10 years of follow-up and then analyzed
      retrospectively. Group 1 (n=382) received 2 internal thoracic artery grafts,
      Group 2 (n= 139) received 1 internal thoracic artery graft and 1 saphenous vein
      graft, and Group 3 (n= 173) received 2 saphenous vein grafts. Patient
      demographics, preoperative angiographic findings, and operative indications were
      the same. Hospital mortality rates were 2.6%, 2.2%, and 2.3%, respectively.
      Hemorrhage, sternal wound infection, mediastinitis, sternal dehiscence, and
      prolonged ventilatory support showed no group differences. Follow-up over 10
      years was complete in 677 survivors. Mortality rates during follow-up were 1.8%,
      2.9%, and 4.7%, respectively. Cardiac-related mortality rates were 71%, 75%, and
      88%, respectively (Group 1 vs Group 3, P=0.0412). Ten-year survival was better
      for Group 1 than for Groups 2 and 3 (P=0.0356 and P <0.0001). Cardiac-event-free
      survival at 10 years was 93% in Group 1, 84% in Group 2, and 74% in Group 3 (all
      P <0.0001). The use of 2 internal thoracic artery grafts resulted in
      significantly lower risk of cardiac death and re-intervention, compared with the
      use of 1 internal thoracic artery, which in turn was superior to the use of vein
      grafts. Use of double internal thoracic arteries did not increase postoperative
      complications.

PMID- 11453140
TI  - Jam today?

PMID- 11453139
TI  - Tricuspid repair for infective endocarditis: clinical and echocardiographic
      results.
AB  - We report our retrospective experience in the treatment of infective tricuspid
      endocarditis with valve repair From January 1981 through January 1999, 238 cases
      of infective endocarditis were seen at our institution, with tricuspid
      involvement in 19 cases. Tricuspid valve repair was performed in 9 patients whose
      valves had infective lesions involving a single leaflet. One goal of the repair
      was to avoid implanting any prosthetic material. At surgery, the posterior
      leaflet was completely excised and annuloplasty was performed in 4 patients. Wide
      quadrangular resection of the anterior leaflet and De Vega annuloplasty were
      performed in the other 5 patients. All patients had a good postoperative recovery
      Postoperative echocardiography showed no tricuspid regurgitation in 4 patients,
      mild regurgitation in 3, and moderate in 2. Follow-up ranged from 21 to 155
      months (mean, 4756 +/- 50 [SD] months). Two late deaths occurred: one, 2 months
      postoperatively (sudden death), and the other, 108 months postoperatively (lung
      carcinoma). Late postoperative echocardiography showed no tricuspid regurgitation
      in 4 patients, mild in 2, and moderate in 2. No recurrent infection was observed.
      Tricuspid valve repair rather than valvulectomy or replacement is indicated in
      cases of right-sided endocarditis with single-leaflet involvement. Tricuspid
      repair enables eradication of the infection without implantation of prosthetic
      material.

PMID- 11453141
TI  - Hand-searching for systematic reviews.

PMID- 11453142
TI  - Fluoride prescribing.

PMID- 11453143
TI  - Tooth notations.

PMID- 11453144
TI  - Needle stick injury.

PMID- 11453145
TI  - Community care.

PMID- 11453146
TI  - Emergency prescribing.

PMID- 11453147
TI  - Hazards of prophylaxis.

PMID- 11453148
TI  - The true picture.

PMID- 11453149
TI  - Journals and books appeal for library.

PMID- 11453150
TI  - Fluoridation jinks.

PMID- 11453151
TI  - Women in dentistry.

PMID- 11453152
TI  - Evidence-based dentistry: an overview of the challenges in changing professional
      practice.
AB  - A great deal of effort and resources are currently being directed at developing
      an evidence-based approach to healthcare delivery. The success of the evidence
      based movement will depend upon the provision of necessary support to help GDPs
      achieve change. This paper aims to give an overview of current knowledge on what
      types of interventions are most effective at changing health professionals'
      clinical practices. Barriers to change are highlighted and the implications for
      the development of evidence-based dentistry are considered. Further research on
      organisational, social and personal influences affecting the application of
      evidence-based practice is necessary.

PMID- 11453153
TI  - Gathering information 1: basics.

PMID- 11453154
TI  - Management of needlestick injuries in general dental practice.
AB  - The objective of this paper is to advise on the development of practical policies
      for needlestick injuries in general dental practice. Policies for dealing with
      occupational exposure to chronic blood borne viruses, namely, hepatitis B, C and
      HIV are evolving. This article was particularly prompted by recent changes in
      post exposure prophylaxis for HIV infection. A flow chart is also included which
      should be of possible use in general dental practice. Needlestick injuries are of
      increasing concern to healthcare workers. Successful prophylaxis requires careful
      planning in advance. Whilst all practices should have a policy for sharps
      injuries, prevention of needlestick injuries remains the best policy.

PMID- 11453155
TI  - The reasons for extraction of permanent teeth in Scotland: a 15-year follow-up
      study.
AB  - AIMS: Although Scotland has the highest proportion of edentulous adults in the
      UK, the frequency of edentulousness has fallen by 21% during the last 20 years.
      This study, carried out in 1999, was designed to establish whether the reasons
      for tooth loss have also changed since 1984 when they were last determined.
      METHODS: The Scottish Dental Practice Board provided the names of every fourth
      dentist on its list among which 425 general dental practitioners were identified.
      They were asked to record permanent tooth extractions for 1 week, specifying the
      age, sex and dental attendance of patients who underwent extractions and the
      reasons for these extractions. 352 dentists took part: a response rate of 82.8%.
      RESULTS: The study confirmed that there has been a reduction in the number of
      extractions between 1984 and 1999: there were 25% fewer teeth extracted per
      patient and 30% fewer per dentist per week. From 0-20 years of age, orthodontics
      has replaced caries as the commonest reason for extraction and in all age groups
      over 20 years, caries has become the commonest reason in contrast to 1984 when
      periodontal disease was the principal reason in patients over 40 years old.
      CONCLUSIONS: Caries and its sequelae remain the most important cause of tooth
      loss throughout adult life in Scotland and, therefore, caries prevention and
      maintenance of restorations are of great importance at all ages.

PMID- 11453156
TI  - A clinical minimum data set for primary dental care.
AB  - OBJECTIVE: To achieve consensus within primary dental care on the contents of a
      clinical minimum data set to measure oral health status. DESIGN: Using the Delphi
      process a simple random sample of 30 LDCs and 10 CDS services in England were
      asked to rank a list of existing clinical indicators in order of their perceived
      importance as a means of measuring oral health. A nominated panel representing
      the stakeholder organisations of primary dental care reviewed this ranking and
      identified a core group of clinical indicators to be included in a clinical
      minimum data set. RESULTS: An 80 percent response rate to the Delphi process was
      achieved. Consensus was reached on a core group of 10 indicators, which can
      provide information on patient's perceptions of pain, function and appearance,
      and professional measurements of caries, teeth present, periodontal disease, oral
      sepsis, presence of mucosal pathology and tooth wear. CONCLUSIONS: A
      representative sample of primary care dentists in England and the key
      representative organisations of primary dental care achieved consensus on the
      contents of a clinical minimum data set to record oral health status in primary
      dental care. This is a first step in standardising the measurement of oral health
      status across primary care.

PMID- 11453157
TI  - Evaluation of a computer-assisted learning programme on the oro-facial signs of
      child physical abuse (non-accidental injury) by general dental practitioners.
AB  - A computer-assisted learning programme with tutorials and self assessment
      multiple choice questions has been developed. One hundred and two general dental
      practitioners were asked to evaluate the programme. Over 80% of respondents felt
      that the programme was easy to use, contained an appropriate level of supporting
      information, and had improved their knowledge of non-accidental injury. All users
      of the programme felt that it was a better way of learning than video, audio
      tapes, and journals or books on the subject. It is concluded that CAL programmes
      are worthwhile for providing continuing professional education for general dental
      practitioners.

PMID- 11453158
TI  - Statement of intent--MFDS/MFD new regulations 2001.

PMID- 11453159
TI  - National Dental Conference: Best Practice 2001.

PMID- 11453160
TI  - Expression of the human NOV gene in first trimester fetal tissues.
AB  - NOV, located on human chromosome 8q24.1, was originally cloned following
      discovery of its avian homolog as a consequence of over-expression in virally
      induced nephroblastoma. The gene product is a secreted, modular, protein and a
      member of the CCN gene family. Evidence to date indicates that the expression of
      the wild type protein is associated with cellular quiescence in normal embryonic
      fibroblasts yet produces growth stimulatory effects on established murine NIH 3T3
      cells. Here we report the expression of NOV in the first trimester of human
      embryogenesis, between 5 and 10 weeks. In situ hybridisation and
      immunohistochemistry reveal widespread expression in derivatives of all three
      germ layers. The most abundant sites of expression are in the motor neurons and
      floor plate of the spinal cord, adrenal cortex, fusing skeletal, and smooth
      muscle, the urogenital system and the developing heart. Additionally, expression
      is seen in the cranial ganglia, differentiating chondrocytes, gonads, and lung.
      The sites of expression suggest strongly that autocrine or paracrine expression
      of NOV is associated with the process of cell differentiation.

PMID- 11453161
TI  - Functional organization of the dorsal cochlear nucleus of the horseshoe bat
      (Rhinolophus rouxi) studied by GABA and glycine immunocytochemistry and electron
      microscopy.
AB  - Unique among mammals, the dorsal cochlear nucleus (DCN) of horseshoe bats
      consists of two functionally and anatomically distinct subdivisions: a laminated
      ventral portion that processes the frequency range below the constant frequency
      (CF) component of the echolocation signal and a nonlaminated dorsal portion that
      is specialized for processing the CF-signal range (76 kHz and higher). Using
      conventional transmission electron microscopy and postembedding
      immunocytochemistry for the inhibitory neurotransmitters GABA and glycine on
      semithin-alternating sections, we present further evidence that the ventral
      laminated subdivision of DCN conserves the main elements of microcircuitry and
      GABA/glycine labeling patterns typical for the mammalian DCN: (i) the main cell
      types and synaptic inventory of the granule cell/cartwheel cell system of the
      superficial layers are present as well as (ii) the tuberculoventral cell system
      of the deep layers. The nonlaminated dorsal subdivision lacks the granule
      cell/cartwheel cell system and is composed of a mixture of fusiform projection
      neurons with tuberculoventral cell analogues. Thus the inhibitory
      tuberculoventral system known to play an important role in temporal and spectral
      processing in VCN is conserved throughout the DCN of horseshoe bats, whereas
      functional components of cerebellar-like circuits are reduced in a specialized
      region that processes the dominant biosonar component.

PMID- 11453162
TI  - Immunocytochemical and ultrastructural characterization of somatolactin cells
      from the gilthead sea bream (Sparus aurata L., Teleostei): an ontogenic study
      (from newly hatched to adults).
AB  - For the first time, somatolactin (SL) cells have been ultrastructurally
      identified and characterized during the ontogeny of gilthead sea bream, Sparus
      aurata, using specimens ranging in age from hatching to 15 months. The SL cells
      were identified by an immunogold method using anti-cod SL serum. The SL
      immunoreactivity was mostly located on the secretory granules of the cells,
      although some vesicles of variable size and shape with a medium electron-dense
      content, and some irregular secretory granules and polymorphic or very irregular
      masses that can arise from the fusion of several secretory granules, also
      presented immunogold labeling. In adults, the SL cells were mainly found in the
      pars intermedia, where they were organized in discontinuous cell cords lying
      against the neurohypophysis or surrounding the neurohypophyseal branches. Some SL
      cells, however, appeared isolated or in small groups in the pars intermedia, in
      the proximal pars distalis and, rarely, in the rostral pars distalis. The SL
      cells were variable in shape, with processes directed towards the neurohypophysis
      or blood vessels, or intermingling among other adenohypophyseal cells. The
      secretory granules were mostly round, although some were oval, bilobate or pear
      shaped, with a homogeneous, very electron-dense content and a narrow, dense or
      clear, halo. Different SL cell populations can be distinguished according to
      secretory granule size. Our findings indicate that SL is stored in the secretory
      granules and released by exocytosis. SL cells showing involutive features were
      only found in adults. SL cells can be ultrastructurally identified in one-day-old
      larvae although similar characteristics to those found in adults can be
      positively identified only after 4 days. Secretory granules increased in number,
      size and heterogeneity during development. Synaptic-like structures between axon
      terminals of the neurohypophysis and the SL cells were found in larvae from one
      day-old onwards. In juveniles of 118 days of age, two different populations of
      secretory granules (immunogold-labeled and non-immunogold-labeled) can be found
      in the same or different SL cells, findings that suggest the existence of two
      different molecular forms of SL at this age. There was a clear increase in the
      complexity of the pituitary gland and in the heterogeneity of the SL cells during
      development, the latter observation probably reflecting different functional cell
      stages or production of SL molecules.

PMID- 11453163
TI  - Ontogeny of immunoreactive somatolactin, prolactin and growth hormone secretory
      cells in the developing pituitary gland of Cichlasoma dimerus (Teleostei,
      Perciformes).
AB  - Prolactin, growth hormone and somatolactin constitute a hormone family because
      they are structurally related and are secreted by acidophilic cells of different
      regions of the adenohypohyisis. In this work, we report the ontogeny of ir
      prolactin, ir-growth hormone and ir-somatolactin cells in the developing
      pituitary gland of the cichlid fish Cichlasoma dimerus (Teleostei; Perciformes).
      Antisera raised against fish pituitary hormones were used. In this species
      hatching occurs 54 hs after fertilization and the three different cell types were
      recognized two days later. The neurohypophysis was recognized on day 14 after
      hatching and in later stages it began to show the characteristic deep
      interdigitations of the adults. On day 42 (juvenile stage) the distribution of ir
      PRL, ir-GH and ir-SL showed the pattern described for adults of this species. The
      ir-SL cells were not PAS-positive in larvae as they are in adults. This would
      suggest the presence of a nonglycosilated form of somatolactin in early stages of
      development which may coexist in adults with a glycosilated form. The appearence
      of these hormones so early in development suggest their importance in the
      survival of fish larvae but further studies focused on the ontogeny of
      hypothalamic factors that regulate their synthesis and secretion must be
      performed.

PMID- 11453164
TI  - The development of articular cartilage: evidence for an appositional growth
      mechanism.
AB  - It is well-established that cartilage grows by a combination of matrix secretion,
      cell hypertrophy and cell proliferation. The extent to which this growth is by
      appositional, as opposed to interstitial mechanisms, however, remains unclear.
      Using the knee joints of the marsupial Monodelphis domestica to study cartilage
      growth, we have combined an immunohistochemical study of the TGF-beta family of
      cartilage growth and differentiation factors between 30 days postpartum to 8
      months, together with a stereological analysis of cartilage morphology during
      growth. Furthermore, to gain an insight into the generation of the characteristic
      zones within cartilage, we have examined the effects of intra-articular
      administration of bromodeoxyuridine, an agent that is incorporated into DNA
      during cell division and blocks further cell cycling. During early growth, TGF
      beta2 and -beta3 were widely expressed but TGF-beta1 was less so. After the
      formation of the secondary centre of ossification, all isoforms became more
      restricted to the upper half of the tissue depth and their distribution was
      similar to that previously described for IGFs, and PCNA-positive cells.
      Stereological analysis of tissue sections from the femoral condylar cartilage at
      3 and 6 months showed that there was a 17% increase in total cartilage volume but
      a 31% decrease in cell density on a unit volume basis. Finally, cell-cycle
      perturbation with BrDU, which was injected into the knee joints of 3-month-old
      animals and analysed 1 and 4 months post-injection, revealed that the
      chondrocytes occupying the transitional zone were depleted 1 month post
      injection, resulting in thinning of the articular cartilage. This effect was
      reversed 4 months post-injection. Immunohistochemical analysis revealed that BrDU
      treatment altered the expression patterns of all TGF-beta isoforms, with a marked
      reduction in labelling of TGF-beta1 and -beta3 isoforms in the upper half of the
      cartilage depth. Overall, the data lends further support to the notion of
      articular cartilage growing by apposition from the articular surface rather than
      by interstitial mechanisms.

PMID- 11453165
TI  - Does an equivalent of the "ventral node" exist in chick embryos? A scanning
      electron microscopic study.
AB  - The internal organs of vertebrates show species-specific left-right (L-R)
      asymmetries. Questions on the embryonic origin of these asymmetries have been
      fascinating embryologists since the 19th century. During the past years,
      remarkable progress has been made in answering these questions. Evolutionary
      highly conserved molecular signaling cascades have been identified that start
      from Hensen's node and transfer side-specific identity to the embryonic left and
      right halves. However, the question of what initiates these signaling cascades
      has remained unanswered. Studies on mouse embryos have shown that the ventral
      surface of Hensen's node consists of a ciliated epithelium called the ventral
      node. Recent findings suggest that the monocilia of ventral nodel cells generate
      a leftward flow of extracellular fluid possibly leading to the accumulation of an
      unknown morphogen at the left of the node, which then might start the signaling
      cascades. This hypothesis might explain the fact that gene defects causing
      ciliary dyskinesia are frequently associated with situs anomalies. Studies on
      chick embryos led to the discovery of the L-R signaling cascades. However,
      whether an equivalent of the ventral node exists in avian embryos remained
      unknown. Therefore, I examined the endoderm and epiblast of early chick embryos
      for the presence of monociliated cells. In the endoderm, a population of
      monociliated cells indeed was present. These cells, however, were neither
      confined to the area of Hensen's node nor did they form the predominant cell
      population at this location. In the epiblast, monociliated cells formed the
      predominant cell population at the periphery of the blastodisc but only a
      relatively small subpopulation of epiblast cells at Hensen's node. These findings
      suggest that, in the early chick embryo, an equivalent of the ventral node of
      mouse embryos neither exists on the ventral nor the dorsal surface of Hensen's
      node. It is unlikely that nodal cilia are required for initiating the L-R
      patterning in chick embryos.

PMID- 11453166
TI  - Distribution of [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites in rat
      hippocampal long-term slice cultures isolated from external afferents.
AB  - The distribution of ionotropic glutamate receptors in transverse hippocampal
      sections and along the septotemporal hippocampal axis can be correlated to
      hippocampal connectivity, in particular to area- and layer-specific termination
      zones of afferents. However, in isolated organotypic hippocampal slice cultures
      developing without extrinsic afferent input no systematic studies exist about the
      distribution of glutamate receptors. In the present study we used receptor
      autoradiography to examine [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites in
      hippocampal slice cultures prepared from 6-day-old rats. After 24 days in vitro
      layer-specific concentrations of [3H]MK-801, [3H]AMPA and [3H]Kainate binding
      sites were compared to age-matched hippocampi in situ (P30 rats). An obvious
      difference between hippocampal slice cultures and hippocampi in situ was a
      changed distribution of binding sites among the hippocampal areas showing a
      relative increase of [3H]MK-801 and [3H]AMPA binding sites in CA3 as compared to
      CA1 and to the dentate gyrus in the cultures. In CA1, however, the relative layer
      specific distributions of [3H]MK-801 and [3H]AMPA binding sites were identical in
      hippocampal slice cultures and in hippocampi in situ. Interestingly, layer
      specific binding of [3H]Kainate in the cultures exceeded that in the hippocampi
      in situ 3-5 times. Moreover, in the cultures the binding of the three ligands
      varied systematically showing gradients along the "superficiomembranal" axis.
      Cultures taken from different positions along the hippocampal axis differed with
      respect to concentrations of [3H]MK-801 and [3H]Kainate binding sites, but not of
      [3H]AMPA binding sites. The results suggest a massive sprouting and
      reorganisation of intrinsic projections in long-term hippocampal slice cultures.

PMID- 11453167
TI  - Therapists' beliefs about research and the scientist-practitioner model in an
      evidence-based health care climate: a qualitative study.
AB  - The growing emphasis on achieving therapeutic practice that is informed by
      research evidence or 'evidence-based' has been well documented. However, if
      therapists are to operate effectively within evidence-based services, it is
      necessary to develop a better understanding of factors that influence their
      attitudes towards research in routine clinical work. Within this context, there
      is a need to re-examine the scientist-practitioner model as potentially
      complementing or competing with evidence-based practice. This study explores the
      beliefs about research and the scientist-practitioner model amongst a diverse
      group of therapists whose work is contextualized by evidence-based practice. In
      depth, qualitative interviews were used to elicit significant themes that related
      to current practices, previous training and contact with other professionals. The
      findings suggest that the therapists' beliefs were shaped by different levels of
      influence that range from personal values to organizational and political issues.
      The results also highlighted how the therapists had constructed more
      idiosyncratic definitions of the scientist-practitioner model that related to
      perceptions of its value. Implications for further research, training and
      practice are discussed.

PMID- 11453168
TI  - Severe intellectual disability and transition to adulthood.
AB  - Institutional and psychological aspects of transition were explored with parents
      and staff involved with five young adults with severe intellectual disability
      whose challenging behaviour diminished after they made the transition, and five
      whose challenging behaviour remained high. They were selected from a previously
      surveyed cohort. Grounded theory analysis of interviews suggested little
      connection between the perspectives of parents and staff. The impact these
      differences have on communication about challenging behaviour was explored, and
      recommendations for service changes are made.

PMID- 11453169
TI  - Experimentally induced emotions, facial muscle activity, and respiratory
      resistance in asthmatic and non-asthmatic individuals.
AB  - We studied the effects of emotion induction on total respiratory resistance, and
      their relationship with cardiac vagal activity and facial muscle activity in
      asthma. Groups of 20 asthmatic and 20 non-asthmatic participants were exposed to
      series of happy and depressing pictures or self-referent Velten statements.
      Facial electromyographic activity over corrugator supercilii, orbicularis oculi,
      and zygomaticus major regions was recorded during periods of presentation and
      imagery of each stimulus. Following each stimulus series, mood, respiratory
      resistance, ventilation, and cardiac activity including respiratory sinus
      arrhythmia (RSA) were recorded. Significant increases of respiratory resistance
      were observed in asthmatic patients following depressing stimulation. Resistance
      increases were positively correlated with RSA and heart period. No substantial
      group differences were found in facial response to emotional stimuli. Changes in
      facial target muscle sites during positive stimulation were inversely correlated
      with RSA following stimulation. We conclude that respiratory resistance increases
      in asthmatics following depressing stimulation are dependent on vagal activity.
      Greater facial muscle activation during emotional stimulation can reduce vagal
      activation, which is consistent with claims in the clinical literature of the
      benefits of emotional expression in asthma.

PMID- 11453170
TI  - Psychological functioning and bodily conditions in patients with pain disorder
      associated with psychological factors.
AB  - A sample of chronic pain patients (N = 40) was described with reference to
      defence mechanisms, interpersonal problems, psychological symptoms and bodily
      conditions. The relationships between pain intensity and different psychological
      and bodily indexes were examined. The defence mechanisms of somatization and
      denial measured by the Minnesota Multiphasic Personality Inventory (MMPI)
      characterized the sample. Interpersonal relations were typically overly
      nurturant, exploitable, non-assertive and socially avoidant according to the
      circumplex version of Inventory of Interpersonal Problems (IIP-C). Somatization,
      obsession, depression and anxiety were the highest symptom scales on the Symptom
      Check-List 90, revised (SCL-90-R). The Comprehensive Body Examination (CBE)
      produced moderate findings mainly reflecting stiffness, and the intensity of pain
      was medium high. The MMPI psychosomatic pattern, the combined IIP-C index
      consisting of the elevated subscales, and the elevated subscales on SCL-90-R were
      all moderately correlated with pain intensity. Contrary to our prediction, the
      global bodily stiffness score was unrelated to pain.

PMID- 11453171
TI  - A qualitative study of mindfulness-based cognitive therapy for depression.
AB  - Psychotherapeutic interventions containing training in mindfulness meditation
      have been shown to help participants with a variety of somatic and psychological
      conditions. Mindfulness-based cognitive therapy (MBCT) is a meditation-based
      psychotherapeutic intervention designed to help reduce the risk of relapse of
      recurrent depression. There is encouraging early evidence from multi-centre
      randomized controlled trials. However, little is known of the process by which
      MBCT may bring therapeutic benefits. This study set out to explore participants'
      accounts of MBCT in the mental-health context. Seven participants were
      interviewed in two phases. Interview data from four participants were obtained in
      the weeks following MBCT. Grounded theory techniques were used to identify
      several categories that combine to describe the ways in which mental-health
      difficulties arose as well as their experiences of MBCT. Three further
      participants who have continued to practise MBCT were interviewed so as to
      further validate, elucidate and extend these categories. The theory suggested
      that the preconceptions and expectations of therapy are important influences on
      later experiences of MBCT. Important areas of therapeutic change ('coming to
      terms') were identified, including the development of mindfulness skills, an
      attitude of acceptance and 'living in the moment'. The development of mindfulness
      skills was seen to hold a key role in the development of change. Generalization
      of these skills to everyday life was seen as important, and several ways in which
      this happened, including the use of breathing spaces, were discussed. The study
      emphasized the role of continued skills practice for participants' therapeutic
      gains. In addition, several of the concepts and categories offered support to
      cognitive accounts of mood disorder and the role of MBCT in reducing relapse.

PMID- 11453172
TI  - Social institutions and psychological explanations: Druze reincarnation as a
      therapeutic resource.
AB  - For Emile Durkheim, to explain our social institutions through individual
      psychology was generally regarded as illegitimate. It has, however, often been
      assumed by psychologists and psychiatrists, particularly in the case of religious
      doctrine and institutions. However, the people actually concerned, our religious
      informants, might sometimes themselves volunteer interpretations which are
      psychologically functional for the origin and maintenance of certain cultural
      facts. This is particularly so when they are faced with a 'modern' worldview. The
      instance of the Druze belief in bodily reincarnation after death is considered in
      the context of the recent civil war in the Lebanon.

PMID- 11453173
TI  - Voices of the self in psychotherapy: a qualitative analysis.
AB  - Approaches that view the self as constituted by socio-cultural processes and as
      plural, consisting of a multiplicity of states, positions, functions, etc., have
      flourished in the last decades. This paper explores the multi-voiced nature of
      the self, drawing upon Lacan's theory of subjectivity and Bakhtin's concept of
      dialogism. Subjectivity is seen as constituted through language as expressed in
      the speech of the subject's important early others. The psychoanalytic concept of
      transference, understood as a semiotic process of enacting early interpersonal
      patterns in the subject's present relations, provides a link between the
      unfolding of subjectivity in the present and its historical continuity. The
      articulation of subjectivity is discussed through a micro-analysis of extracts
      from sessions of a long-term psychoanalytic psychotherapy. The analysis
      demonstrates the enactment of transferential dialogical positions at the
      beginning of the therapy and traces their recognition by the client through the
      gradual development of increasingly reflexive subject positions towards the end
      of therapy. It is argued that the aim of therapy should be the facilitation of a
      complex subjectivity, whereby the different subject positions can be fluently
      articulated within an overall reflexive frame.

PMID- 11453174
TI  - Rated casemix of general practitioner referrals to practice counsellors and
      clinical psychologists: a retrospective survey of a year's caseload.
AB  - Although evidence-based guidelines are beginning to be produced as to which
      psychological therapies might be appropriate for which patients, little is known
      about how general medical practitioners (GPs) in practice distribute referrals
      between different psychological therapy services. In a retrospective survey, 19
      practice counsellors and 10 clinical psychologists from the same geographical
      area rated a year's caseload of GP referrals using identical data collection
      methods. Rated casemix was found to be broadly similar, although practice
      counsellors rated relationship and bereavement problems as more common in their
      caseloads (totalling 986 patients), and clinical psychologists rated panic
      disorder, phobias, and obsessive-compulsive problems as more common in their
      caseloads (totalling 320 patients). Depression and anxiety reactions were the
      most common problems rated in both groups, but the clinical psychologist cases of
      depression were rated as more severe and complex. Where differences were found,
      they may have reflected the different ways that counsellors and clinical
      psychologists conceptualize cases rather than actual differences in casemix. The
      results are discussed in relation to evidence-based guideline recommendations
      about cases appropriate to be seen by practice counsellors and by clinical
      psychologists in primary and secondary care, and the need to adapt such guidance
      to local services and skills of practitioners.

PMID- 11453175
TI  - Translating the psychobiology of post-traumatic stress disorder into clinically
      useful analogy.
AB  - Psychological theorizing about post-traumatic stress disorder (PTSD) has
      developed considerably since early behavioural formulations (Brewin, Dalgleish, &
      Joseph, 1996; Mowrer, 1960) and there have been parallel developments in
      biological understanding (Yehuda, 1998). However clinical practice has not been
      affected by the new psychobiology. It is suggested that it is possible to
      translate this new understanding into a clinically useful analogy that will help
      circumvent the difficulties of forming a therapeutic alliance with trauma victims
      which have been reported (Pitman et al., 1991; Scott & Stradling, 1997).

PMID- 11453176
TI  - 'I'm not picking up a heart-beat': experiences of sonographers giving bad news to
      women during ultrasound scans.
AB  - This study explores the experiences of obstetric sonographers imparting
      diagnostic information which may be considered 'bad news' to expectant mothers.
      Semi-structured interviews were conducted with nine sonographers at two London
      Hospitals to elicit their experiences of giving bad news. Themes which emerged
      then formed the basis for a quantitative survey of 180 practising obstetric
      sonographers in England. Their perception of what constitutes 'bad news' was
      examined. It was found that sonographers were predominantly concerned with lack
      of time and the unpredictability of the patient's reaction when giving bad news.
      Staff working in settings where there was a clear protocol specifying how to
      proceed following disclosure of bad news experienced less stress than those
      working without such a protocol. These findings have implications for
      psychologists working with patients who suffer pregnancy loss who may consider
      provision of support and counselling skills training for sonographers.

PMID- 11453177
TI  - 'Psychotherapist' approaches to gay and lesbian patients/clients.

PMID- 11453178
TI  - Organ transplantation: from myth to reality.

PMID- 11453179
TI  - Morphometric evaluation of tissue-implant reaction associated with ALCAP and TCP
      bioceramics in vivo.
AB  - The purpose of this investigation was to correlate the thickness of the fibrous
      capsule and the various histological components surrounding aluminum-calcium
      phosphate (ALCAP) and tricalcium phosphate (TCP) bioceramics at the subcutaneous
      (sc) and intraperitoneal (ip) implantation sites. The rational of conducting this
      investigation is to further elucidate the mechanisms of tissue-implant
      interaction. Thirteen Sprague-Dawley adult male albino rats were randomly divided
      into three groups. Animals in groups I and II (n = 5/group) were implanted at
      both ip and sc implantation sites with either ALCAP or TCP ceramics,
      respectively. Animals in group III (n = 3) were not implanted and served as the
      intact control for the comparative purposes. At 90 days postimplantation, the
      animals in all groups were euthanized (Ketamine/Zylazane) and the fibrous tissue
      surrounding the ceramic devices was retrieved. After routine histological
      processing, sections (5 microm) of tissue was stained with hematoxylin and eosin
      (H&E) and evaluated using light microscopy. With the exception ofneutrophils, at
      both implantation sites, the fibrous tissues surrounding the TCP bioceramics
      demonstrated greater capsular thickness, more vascularity, and more macrophages,
      fibroblasts, and collagen than those surrounding the ALCAP ceramic. Data obtained
      from this investigation provided further insights into the differences in the
      tissue-implant responses of calcium-phosphate-based ceramics and the cellular
      composition of the fibrous tissue reaction found at sc and ip implantation sites.

PMID- 11453180
TI  - A preparation to study simultaneous arterial and venous thrombus formation in
      rabbits.
AB  - Injury to an artery induces formation of a platelet-rich thrombus, while stasis
      or trauma to a vein induces a fibrin-rich thrombus. We have implemented
      preparations for evolving both platelet-rich and fibrin-rich thrombi
      simultaneously in rabbits for use to define the efficacy of novel antithrombotic
      agents. For platelet-rich thrombosis, a carotid artery and contralateral jugular
      vein were dissected and an arteriovenous shunt inserted distally to prevent
      cerebral infarction during thrombus formation. The shunted artery was then
      instrumented with a proximal Doppler probe for measuring flow velocity and a
      distal transluminal needle electrode. Electrical injury to the artery was induced
      by application of 250 microA of anodal current to the indwelling needle
      electrode. Thrombotic occlusion was consistently observed within 60 min,
      permitting measurements of the effects on the incidence and time of occlusion of
      antithrombotic agents administered over 2 h. For fibrin-rich thrombosis, an
      external jugular vein was dissected, including the distal bifurcation. One of the
      branches was catheterized and a copper wire with cotton threads attached was
      advanced through the catheter into the superior vena cava, allowing exposure of
      the threads to flowing blood. A 25- to 30-mg thrombus was formed within 2 h,
      permitting reliable measurements of effects on thrombus weight of antithrombotic
      agents administered during this interval. Implementing both arterial and venous
      thrombosis simultaneously did not change measurements compared with either method
      alone. This approach may facilitate recognition of differences in efficacy of
      selected agents against thrombi of diverse composition.

PMID- 11453181
TI  - Suture-line reinforcement with glutaraldehyde-preserved bovine pericardium for
      nonanatomic resection of lung tissue.
AB  - In this study we assessed the usefulness of glutaraldehyde-preserved bovine
      pericardium (GPBP), preparated in our laboratory, in nonanatomic resection of
      lung tissue in dogs. A 30% resection of the right cranial lobe of the lung was
      performed in 18 mongrel dogs. The suture line was reinforced with GPBP strips.
      For group I (n = 6), the GPBP strips were fixed on the lung with nonabsorbable
      suture by thoracotomy. In Group II (n = 6), the resection and fixation of the
      GPBP strips were performed with an endoscopic linear stapler by thoracotomy. In
      Group III (n = 6), the resection and fixation of the GPBP strips were performed
      with a linear stapler by thoracoscopy. The animals were evaluated each day during
      the first week after surgery and every other day during the study time. At the
      end of the study all animals were euthanized with an overdose of pentobarbital.
      Macroscopic and microscopic examinations of the bioprosthesis and lung were
      evaluated. All animals survived the surgical procedure and study time (8 weeks).
      In the three groups, macroscopic examination of the bioprosthesis showed good
      adaptation to the lung tissue. Microscopically, all groups of animals presented
      good healing, with the presence of fibrotic tissue layer on the GPBP and its
      periphery as well as in the lung. However, in group I we observed the presence of
      giant cells in the suture line. GPBP proved to be a useful material for
      reinforcement of the nonanatomic resection suture line of lung tissue in dogs.

PMID- 11453182
TI  - Use of an isolated joint model to detect early changes induced by intra-articular
      injection of paclitaxel-impregnated polymeric microspheres.
AB  - Paclitaxel is a chemotherapeutic agent that suppresses cellular proliferation and
      angiogenesis and has been effective in suppressing proliferative synovitis in
      animal models. Local joint delivery ofpaclitaxel is being pursued as a treatment
      for rheumatoid arthritis in humans, to avoid systematic toxicity of the drug. We
      used an extracorporeal, isolated metacarpophalangeal joint preparation that
      uniquely permitted the simultaneous evaluation of codependent hemodynamic,
      microvascular, and transsynovial flow responses of a joint. Specifically in this
      study, the isolated joint preparation provided quantitative assessment of
      vascular flow, transsynovial flow, and morphologic changes in response to
      intraarticular injection of paclitaxel (50 ng) in poly-(DL)-lactide co-glycolide
      50:50 microspheres (50 microm diameter) to assess initial intra-articular
      biocompatibility. Control joints were isolated but not injected. Serial
      hemodynamic measurements, transsynovial fluid forces, synovial fluid analysis,
      synovial and capillary permeability, and oxygen metabolism were measured every 30
      min during a subsequent 3-h isolation period. At termination, synovium and
      cartilage were harvested from bilateral metacarpophalangeal joints for
      histopathologic assessment. Intra-articular injection of this formulation of
      paclitaxel did not significantly affect hemodynamic parameters in the joint
      during this short-term study, and early joint inflammatory reaction was minimal.
      However, transsynovial fluid forces were significantly greater in treated joints
      as evidenced by greater synovial fluid flow, intra-articular pressure,
      transitional microvascular pressure, and permeability to fluid transport. Gross
      and histologic morphology of synovium and articular cartilage were normal in all
      isolated joints. In conclusion, this extracorporeal in vivo isolated joint model
      permitted investigation of the early changes in joint physiology induced by this
      microsphere formulation and dose ofpaclitaxel in joints and could provide a more
      physiologic and dynamic model for study of the pharmacokinetics of drug
      absorption following intra-articular administration. Due to the minimal
      inflammation and lack of evidence of gross or histologic change in the joint,
      this formulation of paclitaxel should be adequately biocompatible for use in an
      in vivo animal model for further study of its feasibility for human use.

PMID- 11453183
TI  - Problems in Silverman's work indicate the need for a new approach to research on
      subliminal psychodynamic activation.
AB  - The basic assumption in subliminal psychodynamic activation research is that
      participants can unconsciously perceive the psychodynamic meaning of a complete
      message as it is intended by the experimenter. In attempts to account for
      negative findings Silverman contended that this assumption holds only under
      certain luminance conditions and visual field positions of a message.
      Paradoxically, almost all of his findings, his major evidence in support of the
      basic assumption, came from experiments in violation of those strictures.
      Further, Silverman never presented MOMMY AND I ARE ONE under a critical condition
      required for it to be effective. These and other considerations identify the need
      for an account of empirical findings other than his and for changes in his
      experimental method. Such research must take into account the encoding of
      subliminal stimuli, an area neglected almost completely by Silverman. Shevrin and
      his colleagues' 1996 work is outlined as a model for the use of subliminal
      stimuli to investigate psychoanalytically generated hypotheses.

PMID- 11453184
TI  - Lateral asymmetries in attentional priming during a semantic and a visuospatial
      task.
AB  - This study tests the hypothesis that lateral cueing of attention activates the
      contralateral hemisphere and also that performance on a semantic and a
      visuospatial task will differentially be affected depending on the visual field
      (right or left) to which attention was drawn. In an experimental setting, 68
      subjects performed both a semantic and a visuospatial discriminating task,
      whereby visual priming signals unbeknownst were presented to either the left or
      the right visual field. For the semantic task (which is believed to engage
      primarily the left hemisphere) priming signals enhanced performance more when
      they were presented to the right visual field. For the visuospatial task, no
      difference was found between priming signals presented in either visual field.
      While there may be several alternative explanations for the observed difference
      in the effects of the priming signals presented to different visual fields, the
      importance of separating the components inherent in the tasks is stressed. While
      the process of decision-making may involve different relative activation of the
      two hemispheres, depending on whether the stimuli are semantic or visuospatial in
      nature, performance on the task also involves manual coordination which will
      depend especially on motor activation in the left hemisphere.

PMID- 11453185
TI  - Spatial perspective-taking errors in children.
AB  - Spatial perspective-taking was examined in 49 children between the ages of 3.3
      and 10.9 yr. Participants completed (a) a screening test in which they matched
      pictures of a scene to the actual scene and (b) procedures designed to
      differentiate four types of spatial errors: left-right, before-behind,
      egocentric, and random. Among those who passed the screening test the most common
      mistake was to choose a picture that depicted a left-right reversal of the scene,
      and there were relatively few egocentric errors. Even our youngest group made
      mistakes on only 21% of the trials that tested for egocentric responses. The
      pattern of results implied that perspective reversals of left and right were the
      likely origin of many mistakes that have been interpreted as egocentric in
      previous research.

PMID- 11453186
TI  - Myopia and night-time lighting during sleep in children and adults.
AB  - This cross-sectional study investigated the relationship between different
      lighting conditions experienced during sleep in the first -two years of life and
      development of myopia after age two as reported retrospectively by parents in a
      total of 469 individuals, including 252 children aged 2-16 yr., and 217 adults
      aged 17-40 yr. There were no significant differences in incidence of myopia in
      children who had slept from 0-2 yr. in darkness, with a night light, room light,
      or hall light. Adults who were reported by their parents to have slept with a
      night light on from 0-2 yr. were significantly more likely to be myopic than
      those who were reported to have slept from 0-2 yr. in any other lighting
      condition.

PMID- 11453187
TI  - Perception of sports photographs: a multidimensional scaling analysis.
AB  - Some sports photographs are remarkable for how animate they appear, whereas
      others seem particularly static or frozen. To explore the aspects of still
      photographs that might produce a sense of action, 34 observers viewed all
      possible pairs of 14 previously published images depicting sports figures in
      action and were asked to judge their similarity under two conditions, image-focus
      (how similar are the images) or movement-focus (how similar is the type of
      movement). A separate group of observers also rated each image on eight scales.
      Multidimensional scaling analyses suggested that in the image-focus condition,
      subjects tended to organize their judgments around three general dimensions,
      e.g., on-ground versus off-ground, while in the movement-focus condition the
      subjects were more likely to cluster the images along the lines of the particular
      activity, throwing, running, or jumping. We discuss the problem of movement
      depiction in sports photographs and make suggestions for research on the effects
      of facial expressions, muscular strain, and amount of limb extension.

PMID- 11453188
TI  - Geophysical variables and behavior: CIII. Days with sudden infant deaths and
      cardiac arrhythmias in adults share a factor with PC1 geomagnetic pulsations:
      implications for pursuing mechanism.
AB  - If geomagnetic-mediated stimuli trigger many sudden infant deaths, then the days
      in which they and hospital admissions for cardiac arrhythmias for adults occur
      should share a similar source of variance. Factor analyses of the days in which a
      sudden infant death occurred in Ontario or adults were admitted for one of eight
      categories of cardiac crisis in the Sudbury (Ontario) Region for the year 1984
      supported the hypothesis. This factor, with which infant deaths and adult cardiac
      arrhythmias each shared about 40% of their variance, also shared about 40% of the
      variance with a factor with which about 35% of the variance in daily occurrence
      of geomagnetic pulsations (0.2 Hz to 5 Hz) was associated. These results are
      consistent with the important role of geomagnetic variables in the occurrence of
      transient electrical anomalies in brain function rather than cardiac blood flow.

PMID- 11453189
TI  - Sprain of the neck in clinically treated patients in The Netherlands: an
      inventory of different categories of car accidents.
AB  - Different categories of car accidents of victims with sprain of the neck were
      investigated for both drivers and passengers. The predominant category of the car
      crash was a collision with another car for drivers as well as for passengers. The
      second cause was unknown. The distribution of the accidents was statistically
      significantly different for drivers and passengers.

PMID- 11453190
TI  - Enhanced brainstem and cortical evoked response amplitudes: single-trial
      covariance analysis.
AB  - The purpose of the present study was to develop analytic procedures that improve
      the definition of sensory evoked response components. Such procedures could
      benefit all recordings but would especially benefit difficult recordings where
      many trials are contaminated by muscle and movement artifacts. First, cross
      correlation and latency adjustment analyses were applied to the human brainstem
      frequency-following response and cortical auditory evoked response recorded on
      the same trials. Lagged cross-correlation functions were computed, for each of 17
      subjects, between single-trial data and templates consisting of the sinusoid
      stimulus waveform for the brainstem response and the subject's own smoothed
      averaged evoked response P2 component for the cortical response. Trials were
      considered in the analysis only if the maximum correlation-squared (r2) exceeded
      .5 (negatively correlated trials were thus included). Identical correlation
      coefficients may be based on signals with quite different amplitudes, but it is
      possible to assess amplitude by the nonnormalized covariance function. Next, an
      algorithm is applied in which each trial with negative covariance is matched to a
      trial with similar, but positive, covariance and these matched-trial pairs are
      deleted. When an evoked response signal is present in the data, the majority of
      trials positively correlate with the template. Thus, a residual of positively
      correlated trials remains after matched covariance trials are deleted. When these
      residual trials are averaged, the resulting brainstem and cortical responses show
      greatly enhanced amplitudes. This result supports the utility of this analysis
      technique in clarifying and assessing evoked response signals.

PMID- 11453191
TI  - Geophysical variables and behavior: CIV. Power-frequency magnetic field
      transients (5 microtesla) and reports of haunt experiences within an
      electronically dense house.
AB  - Magnetic field measurements for power frequencies were measured continuously over
      two 24-hr. periods for a small house in which two adults who exhibited above
      normal occurrences of complex partial epileptic-like experiences had reported
      "waves of fear", tactile sensations, nightmares, apparitions, and a sensed
      presence. The experiences occurred within an area in which irregular amplitude
      modulations between 1 microT and 5 microT (50 mG) from 60-Hz sources, with
      durations of a few seconds to several tens of seconds, were measured. This case
      suggests that transient, complex temporal patterns of power-frequency magnetic
      fields generated by less than optimal grounding in dwellings and telluric
      currents may be sufficient to evoke experiences in the brains of sensitive
      individuals. Cultural labels, applied by the experients, then affect the
      explanations and expectancies for these experiences.

PMID- 11453192
TI  - Implicit theories of creativity: laypersons' perceptions of the creativity of
      adaptors and innovators.
AB  - Kirton has put forward a theory of creativity style in which he maintains that
      people with more adaptive or more innovative orientations possess equal creative
      potential. The purpose of this study was to compare Kirton's explicit theory with
      laypersons' implicit theories of creativity. Laypersons and students were asked
      to read descriptions of adaptors and innovators and then, using their own
      personal conceptions of creativity, rate adaptors and innovators on creativity.
      Analysis showed that the innovative style was perceived as significantly more
      creative. Furthermore, individuals who possessed a more innovative style were
      much more likely to rate the innovative orientation as more highly creative.
      Potential reasons for the implicit view that innovators are more creative are
      offered. In particular, cultural biases towards the innovative style are
      discussed.

PMID- 11453193
TI  - Neuropsychological assessment of battered women: a pilot study.
AB  - Mean performance of 19 battered women was significantly lower than that of 9
      control women on the Halstead-Reitan Neuropsychological Battery, the Wechsler
      Memory Scale-Revised, and the Quick Neurological Screening Test. 58% of the
      battered women scored in the impaired range on the Halstead-Reitan Impairment
      Index; and 53% scored in the impaired range on the Quick Neurological Screening
      Test. More definitive research was recommended.

PMID- 11453194
TI  - Drug-induced variations in the probability of occurrence of multiple corrective
      saccades.
AB  - The amplitude of goal-directed 10 degrees elicited saccades and the probability
      that the main saccade will be followed by multiple corrective saccades increased
      significantly for 10 subjects after Scopolamine treatment (0.5-mg intramuscularly
      injected). The results suggest a perceptual rather than a motor effect for the
      drug.

PMID- 11453195
TI  - Changes in the constraints of semantic and syntactic congruity on memory across
      three age groups.
AB  - 20 college undergraduates, 25 sixth-grade, and 31 second-grade students studied
      targets embedded in three types of sentence contexts and then performed free
      recall and cued recall tests. Although there were no differences in performance
      of free recall among sentence types within each age group, the differences in
      cued recall among sentence types were observed. For sixth graders and
      undergraduates, both semantically congruous/syntactically congruous sentences and
      semantically incongruous/syntactically congruous sentences led to a better cued
      recall of targets than semantically incongruous/syntactically incongruous
      sentences. Second graders performed better in a cued recall of targets in
      semantically congruous/syntactically congruous sentences than for the other two
      sentence types. The results were interpreted as indicating changes across age
      groups in constraints of semantic and syntactic congruity on the spreading
      activation of targets in memory.

PMID- 11453196
TI  - Comparison of tactile awareness in children during the production of isolated
      syllables of English.
AB  - To assess whether lingual-tactile feedback is developmental 60 normally
      developing children formed two groups of 30. Group 1 were in Grades 1 and 2 (M
      age=6.6 yr.) and Group 2 in Grades 5 and 6 (M age=10.7 yr.). All children passed
      a speech, language, and hearing screening. They were asked to imitate the
      production of a syllable, then describe the location of the tongue during that
      production. Following this request, subjects were given four multiple-choice
      questions to answer regarding (a) tongue height (high to low), (b) tongue
      position (front to back), (c) contact with the teeth, and (d) contact with other
      structures within the oral cavity. Seven English phonemes (t, k, sh, r, l, and
      th) were presented in a consonant vowel (CF) syllable with the central carat
      vowel (pronounced "uh"). Children were aided by a two-dimensional line drawing of
      the oral cavity. Mean scores for each syllable ranged from .8 to 2.0 (on a scale
      of 4.0). Total mean scores of 28 possible for older children (M= 11.0) was
      significantly better (t58=-2.2, p<.05) than that for the younger group (M=9.6). A
      significant r58 of .30 (p< .05) was found between age and total syllables
      correct. The children described tongue location during the production of isolated
      syllables. Older children performed the task better, indicating that lingual
      tactile awareness is maturational. These findings parallel the 1967 results of
      McDonald and Aungst who found that identification of oral forms improved across
      age through about 15 years.

PMID- 11453197
TI  - The Poggendorff illusion: effect of distance between the parallel lines.
AB  - 43 subjects observed Poggendorff figures with transverse line segments at a
      constant distance while the parallels were positioned closer or farther apart. At
      closer distances, no illusion occurred; at farther distances, the illusion
      diminished. The illusion no longer occurred when the parallels were located
      beyond the outside end of the transverse lines. Since illusions occurred only
      when the parallels physically touched the transverse line, this research
      emphasizes the importance of the intersection of figural elements in the
      production of the Poggendorff illusion.

PMID- 11453198
TI  - Harter's self-perception profile for children adapted for use with young
      Portuguese students.
AB  - This study of 260 Portuguese early adolescents (Grades 5 to 7; 11-14 years old)
      used a questionnaire which taps six different domains and was devised by Harter
      to evaluate the self-concepts of children and early adolescents in Grades 3 to 7.
      The Portuguese version has Cronbach coefficients alpha between .25 and .80. The
      results of factor analysis and correlational studies evidence a low
      differentiation of the dimensions of self-concept. Results of differential
      studies by sex and school grade indicate girls see themselves as better behaved
      than do boys and boys see themselves as significantly more athletically competent
      than do girls. Also, fifth graders see themselves as more competent in five
      domains of self-concept than do seventh graders.

PMID- 11453199
TI  - The theory of planned behavior as related to intention to exercise and exercise
      behavior.
AB  - In a previously reported study we sought to assess the usefulness of the theory
      of planned behavior in explaining the exercise behavior of 73 adults enrolled in
      an exercise program over a 5-mo. period. The correlation between scores on
      Intention to Exercise and Exercise Behavior was moderate and inverse, conflicting
      with a primary tenet of the Theory of Planned Behavior. In this analysis of the
      data we sought to explain that finding by partitioning participants into groups
      based on a median split of their scores on Intention to Exercise and Exercise
      Behavior. Using the four Intention by Behavior groups as independent variables
      and scale scores as dependent variables, post hoc tests for Fitness Attitude
      showed significant differences only when High Intention conflicted with Low
      Intention, irrespective of Exercise Behavior. Perceived Behavioral Control showed
      opposite tendencies, i.e., differences were significant when High Behavior
      conflicted with Low Behavior, irrespective of Intention to Exercise. We conclude
      that Perceived Behavioral Control defines one's ultimate Exercise Behavior over a
      5-mo. period while scores on Fitness Attitude define Intentions to Exercise.

PMID- 11453200
TI  - Factors which influence the difficulty of the spatial path in Corsi's block
      tapping test.
AB  - Spatial path in Corsi's test is defined as the ideal line joining the blocks
      tapped by the Examiner so the difficulty of the spatial path was analysed vis-a
      vis the numbers of blocks tapped by the Examiner and the number of times the line
      criss-crosses itself through the spatial path. During an experiment with two
      different numbers of blocks and three different numbers of crosses, an analysis
      of variance showed that both factors, i.e., the number of blocks and the number
      of crosses, gave significant results. The experiment showed that it is possible
      to create a series with a decreased number of blocks, but with an increased
      number of crosses, which was more difficult than a series with a greater number
      of blocks but with a decreased number of crosses. Despite this, additional
      significant differences have been found among the series with the same number of
      blocks and crosses, meaning that the variables examined, although important, do
      not solve the problem with the complexity of the spatial path. At this stage, the
      length of the path, measured in millimetres, had to be considered as a further
      source of variance which could explain the difficulty of the spatial path. The
      correlation between path length and mean number correct achieved, through a
      single series of digits utilised in this research, was -.78. This value
      encourages further research.

PMID- 11453201
TI  - Reflective-impulsive style and conceptual tempo in a gross motor task.
AB  - The reflective-impulsive construct refers to responses made slowly or quickly in
      a situation with high uncertainty. Children who are labeled "reflective" take a
      longer time to respond and make few errors, whereas "impulsive" children are fast
      and inaccurate. Although the validity of the test and the definition of
      reflective-impulsive style are well accepted, whether such respond fast or slow
      to all tasks is questioned. Some children do not fit the dichotomy. Two other
      groups arise, the fast-accurate and the slow-inaccurate. The response styles of
      86 boys, ages 5, 7, and 9 years performing a gross motor task, i.e., hitting a
      ball with a racquet, were studied. Analysis indicated that the slowest children
      on the Matching Familiar Figures Test can be faster than the fastest ones and
      remain more accurate. As the definition of the reflective-impulsive style is
      based on time, the reflective ones might better be viewed as children who can
      adapt the response time to the context and thus be more efficient at problem
      solving.

PMID- 11453202
TI  - Tactual performance test trials: psychometric properties of the blocks-per-minute
      scores.
AB  - Internal consistency reliabilities were calculated for the Tactual Performance
      Test blocks-per-minute scores for the Preferred Hand (n=298), Nonpreferred Hand
      (n=302), and Both Hands (n=314) trials, and Total Time. Reliabilities are
      reported for the total sample and three groups of normal, alcoholic, and
      undiagnosed patients sent for assessment. The reliabilities ranged from .6102 to
      .9232. Only three of the discriminate indexes were poor.

PMID- 11453203
TI  - Establishing joint visual attention and pointing in autistic children with no
      functional language.
AB  - Joint visual attention is defined as looking where someone else is looking. The
      purpose of this study was to examine the conditions for establishing joint visual
      attention in autistic children who have no functional speech. An experimenter,
      sitting facing the child, looked at one of six pictures near the child. Analysis
      showed that joint visual attention to stimuli behind the child and therefore
      outside of the visual field occurred at a higher rate when the visual angle
      between the stimuli was about 60 degrees. Spontaneous pointing at the target
      object increased with training which included feedback and physical guidance.
      These results are discussed in terms of the effects of environmental variables
      and perceptual mechanisms on the emergence of joint visual attention in autistic
      children. The possibility of using an adult's social cues and expanding the
      child's visual field as a remedial procedure is also addressed.

PMID- 11453204
TI  - Visual imagery in recognition and source memory for audiotape and text.
AB  - 80 participants heard an audiotape of a crime, read an account with both correct
      and new information, then took recognition and source memory tests. While
      listening and reading, participants attended carefully, and half also formed
      visual images of the events. Imagery instructions had no effects, but recognition
      memory was better for material from the text only than from the audiotape only,
      whereas source memory was better for audiotape than for text. These results
      replicate previous findings for film and audiotape.

PMID- 11453205
TI  - Complexity of rhythmic ability as measured in preschool children.
AB  - There are many aspects which need to be explored before a comprehensive
      description of young children's rhythmic ability can be developed. The present
      study examined the relation of age and sex and preschool children's rhythmic
      ability expressed in performance with one and two hands, bilateral and parallel
      use of upper and lower limbs. Two groups of preschool children participated (N=
      77), 4.5 to 5.5 and 5.6 to 6.5 yr. of age. A version of the High/Scope Beat
      Competence Analysis Test was used to assess rhythmic ability. The children
      performed the same six movements, e.g., parallel movement of hands, bilateral
      movement of hands, movement of the preferred hand, movement of the nonpreferred
      hand, bilateral movement of feet in a seated position, and bilateral movement of
      feet in a standing position. Analysis showed that girls were more accurate than
      boys on bilateral movement of hands while boys were more accurate than girls on
      bilateral movement of feet in a seated position. Also, children were more
      accurate (a) on the movement with the preferred hand than with parallel movement
      of hands and nonpreferred hand movement, (b) on bilateral movement of hands than
      with parallel movement of hands and bilateral movement of feet in a seated
      position, and (c) on bilateral movement of feet while standing than seated. It
      can be concluded that the various rhythmic movements with upper and/or lower
      limbs follow different rates of development in preschool children. The above
      findings may assist physical educators in implementing a physical education
      program more effectively for the corresponding age groups.

PMID- 11453206
TI  - Central and peripheral visual reaction time of soccer players and nonathletes.
AB  - Visual Reaction Time (RT) was measured by presenting three different sizes of
      stimulus to the central and peripheral fields of vision in 6 soccer players and 6
      nonathletes. An electromyogram was recorded from the flexor digitorum
      superficialis muscle of the responding forearm. Peripheral visual RT was longer
      in comparison to central visual RT due to an increment in Premotor Time. The
      soccer players showed shorter Premotor Times during central and peripheral visual
      RT tasks than nonathletes, suggesting that the soccer players are better able to
      respond quickly to a stimulus presented to peripheral as well as central
      positions.

PMID- 11453207
TI  - Effects of sensory feedback on variations on intertap interval and force in
      finger-tapping sequences.
AB  - This study was designed to examine effects of somatosensory feedback on
      variations of intertap interval and muscle force in finger-tapping sequences over
      10 minutes. Although intertap intervals were decreased on the massed task as the
      time passed, the intervals were constant in the distributed task. In finger
      tapping for a long time, impulses perhaps circulate within the loop circuits
      between the cerebral motor cortex and the peripheral nerve and subsequently
      increase further the excitability of the circuits. This increase in the
      excitability within the circuits may shorten the interval and increase variation
      of the interval. On the other hand, although peak force increased up to the 5
      min. mark on the massed task, the force decreased after the 6-min. mark. This
      increase of force also may be produced by increasing activation of the
      corticoperipheral loop circuits. Although the decrease of force was perhaps
      produced by the fatigue of finger muscles for tapping during a few minutes,
      fatigue appeared more clearly in muscle force than in timing control. However,
      the force and the variation were constant in the distributed task.

PMID- 11453208
TI  - Bilingual aphasia and subcortical-cortical lesions.
AB  - The use of the mother tongue relies on implicit memory procedures that are mainly
      controlled by subcortical structures. A second language depends on the integrity
      of the explicit memory system, largely subserved by cortical areas. Therefore,
      bilinguals can be considered as neurolinguistic models which contribute to the
      understanding of how the cortical and subcortical language systems communicate
      while maintaining independent functions. We describe a patient who developed an
      impairment of the mother tongue after an infarct of the caudate. During follow
      up, a dramatic improvement of the mother tongue accompanied by worsening of the
      second language became evident after the extension of the ischemic lesion to the
      cortex.

PMID- 11453209
TI  - Double-coding test: a new paper-and-pencil measure of eye-hand coordination.
AB  - The present research presents the development of a new paper-and-pencil coding
      task that may find a variety of uses in the psychological assessment of cognitive
      processes. The aim of the new test, named the Double-coding Test, was to create a
      more complex task than the previous coding tests. This new task requires two
      different coding processes before marking the correct sign in the appropriate
      space. To validate this new double-coding task it was administered along with the
      Coding B subtest of the Wechsler Intelligence Scale for Children-Revised and the
      d2 Test. Also for validation the new test was administered to a clinical group of
      children having Attention Deficit/Hyperactivity Disorder. A sample of normal
      children is presented for five different ages from 8 and 13 years. Analysis
      showed that the Double-coding Test differentiates between clinical group and
      normal children more effectively than does the WISC-R Coding B subtest or the d2
      Test. Suggestions are offered for use of the Double-coding Test.

PMID- 11453210
TI  - Evaluation of the specificity of selected dynamic balance tests.
AB  - Many researchers have suggested that balance is not a general motor ability but
      rather is specific to the task which is performed. The purpose of the present
      study was to examine the relationship between a laboratory test (stabilometer)
      for assessing dynamic balance and three field tests: the Modified Bass Test,
      Balance Beam Speed Test 1 (forward walking), and Balance Beam Speed Test 2
      (sideward walking). In addition, associations of whole body reaction time with
      scores of the four tests of dynamic balance were assessed in 54 undergraduate
      students. Pearson coefficient of determination indicated no significant
      correlation between the time participants were in balance on the stabilometer and
      on any of the three field tests. Body reaction time was significantly correlated
      with scores on the four tests. These results give further support to the specific
      character of dynamic balance since all tests seemed to measure different aspects.

PMID- 11453211
TI  - Perceptions of power in a first-year collegiate varsity program.
AB  - Analysis of perceptions of a coach's power in a first-year collegiate athletic
      program showed strong similarities between the current data and previously
      published reports of perceptions of power in established athletic programs.

PMID- 11453212
TI  - A study of the self-talk of adults who do and do not stutter.
AB  - This is a preliminary investigation of the differences in positive and negative
      self-talk reported by groups of people who do and do not stutter. 10 people who
      stutter, all who had experience with stuttering therapy, were matched with 10
      participants who did not stutter. Each participant, in both groups, was engaged
      in a session to evaluate speech in a format similar to a professional diagnostic
      session for stuttering. Each participant was asked to stop at specific times
      during the session and describe thoughts of that moment as either positive or
      negative. This procedure is similar to thought sampling and in vivo cognitive
      assessment used in cognitive-behavioral treatments and research. The
      participants' reports were taken during a baseline period, during a period in
      which they were thinking about their speech, and during three different speaking
      tasks. The reports given by the group of people who stutter were compared to the
      reports given by the group of individuals who did not stutter. Statistical
      analyses showed no differences between the thoughts reported by the two groups
      during the entire session, and no differences between groups during the three
      separate tasks (baseline, thinking about their speech, and the speaking tasks).
      Possible explanations and suggestions for research are discussed.

PMID- 11453213
TI  - Physical and occupational therapy undergraduates' stereotypes of one another.
AB  - Literature suggests that increased interaction between physical therapy and
      occupational therapy students may improve their understanding of each other's
      profession. This cross-sectional study examined positive and negative stereotypes
      in an educational setting in which physical and occupational therapy students
      take over 25% of their curricular courses together. The aim of the study was to
      assess whether interaction between these students in and out of the classroom
      positively affected their views of each other, as compared with physical and
      occupational therapy students in previous studies who did not take classes
      together. Senior students, 25 physical therapy and 28 occupational therapy,
      completed two copies of the Health Team Stereotype Scale questionnaire exploring
      attitudes concerning their own chosen profession and the other participants'
      profession. They also completed an extracurricular activities survey to indicate
      how much they participated in activities outside of the classroom with students
      from the other profession. On the stereotype scale, physical therapy students'
      self-assessment compared with their assessment of occupational therapy students
      yielded 28 significantly (p<.05) different adjective pairs; occupational therapy
      students' self-assessment compared with their assessment of physical therapy
      students yielded 26 significantly (p<.05) different adjective pairs. The students
      rarely or never participated in extracurricular activities with each other. When
      comparing present results with those of previous studies, present subjects
      selected significantly fewer negative adjective pairs to describe the other
      profession. The results indicate a more positive view of each other's profession
      than in the previous studies. The interdisciplinary education model examined in
      our institution may have fostered positive attitudes among students in these
      programs.

PMID- 11453214
TI  - The use of actigraphy revised: the value for clinical practice in insomnia.
AB  - In the last years, actigraphy has been used more often for clinical research and
      research evaluation of sleep disorders. Compared to polysomnography, actigraphy
      is cheap and less time-consuming. Actigraphy provides more objective information
      about sleep than sleep logs. Although the algorithms to score sleep and wake
      based on motions measured by actigraphy are still being improved, we believe that
      the role of actigraphy in the clinical evaluation of sleep in insomnia is
      limited. Instead of using actigraphy to distinguish a wakeful state from sleep in
      insomnia, we might better use the activity plots which the actigraph provides to
      get more insight into the physiological hyperarousal or restfulness of insomnia
      patients.

PMID- 11453215
TI  - Detection of facial expressions of emotions in depression.
AB  - Research on perceptual and attentional processes in depression has shown that
      depressed as opposed to nondepressed individuals do not exhibit a positive
      perceptual bias in multistimulus representations. In the present study a face-in
      the-crowd task was applied to examine the relationship between depression and
      spatial detection of facial expression of positive and negative emotions. A face
      in-the-crowd task was administered to 30 subjects (15 clinically stabilized
      depressed inpatients and 15 normal subjects) using displays of schematic faces.
      Depressed subjects showed no performance differences in the detection of negative
      faces and no differences in decision latency for the control condition (all
      neutral faces) compared to normal subjects. Depressed subjects, however, were
      significantly slower in responding to positive faces than normal subjects. Our
      data suggest that depressive mood is associated with a reduced spatial attention
      to positive facial expression and not with an abnormal spatial processing of
      negative facial expression. An implication is that lowered vigilance for facial
      expressions of joy and happiness may affect adversely interpersonal relationships
      in depressed subjects.

PMID- 11453216
TI  - Confirmatory factor analysis of a test used for certification in sport scuba
      diving.
AB  - The purpose of this study was to confirm the underlying factor structure of the
      entry-level scuba diving certification test published by the National Association
      of Underwater Instructors (NAUI). The test measures knowledge mastery across 6
      content areas. A sample of 400 female and male entry-level scuba diving students
      aged from 18 to 47 years participated in the study. A rigorous structural
      equation modeling approach was used to confirm the factor structure of the test.
      The results verify that two latent factors or constructs accurately represent
      knowledge mastery for entry-level scuba diving students. Also, cross-validation
      procedures were used to examine the accuracy of measurement model replication.
      Collectively, these findings support the construct validity of the test.

PMID- 11453217
TI  - Validity of two brief measures: the General Abilities Measure for Adults and the
      Shiple Institute of Living Scale.
AB  - The present investigation examined the concurrent validity of the General Ability
      Measure for Adults by Naglieri and Bardos (1997) and the Shipley Institute of
      Living Scale by Zachary (1991). These scales were administered to 129 college
      students who ranged in age from 18 to 55 years (M age=24.8 yr.). Pearson
      correlations were computed to evaluate the association of scores on these
      measures. Significant small correlations were found for GAMA IQ scores with
      scores on the Shipley Verbal (r = .29) and Total scales (r = .28) but not with
      scores on the Shipley Abstraction subscale (r=.11). Although the GAMA has been
      presented as a measure of general intelligence, only partial support for this
      view was found.

PMID- 11453218
TI  - Relations among age, income, and knowledge of investments.
AB  - This study examined consumers' interactions with financial advisors in terms of
      the age and income of the respondents. The respondents were 500 residents of
      Florida interviewed in a random telephone survey. The dependent variables for the
      analysis were (1) frequency of communication, (2) knowledge, and (3) confidence
      in investment. No significant differences were found for frequency of
      interaction, but differences were identified on both knowledge and confidence in
      investment. Older respondents had more knowledge about investment than did
      younger ones, and respondents of higher income had more knowledge and more
      confidence in their investments than did those of lower or middle income. The
      results are discussed in terms of immediacy theory. Investment issues would have
      more immediacy for higher income respondents since they would have more money
      available for investment. Similarly, immediacy would be higher for older
      respondents since they would have more time and interest to devote to investment
      issues.

PMID- 11453219
TI  - Coefficients alpha for the tactual performance test trials.
AB  - Given the severe assumptions needed for use of the Spearman-Brown reliability
      formula, the Tactual Performance Test trials data described in 2000 were
      reanalyzed using coefficient alpha. These values are considered the best estimate
      of the population reliability for the trials.

PMID- 11453220
TI  - Olfactory sensitivity in early-stage Parkinson patients affected by more marked
      unilateral disorder.
AB  - Two groups of subjects, 6 medicated Parkinson patients at an early stage of
      disease and affected by more marked right unilateral disorder and 12 normal
      elderly people, were examined on matching and naming olfactory tasks. On the
      former, subjects had to recognize among four previously sniffed odours, while on
      the latter they had to label an odour by choosing among four alternatives
      proposed by the examiner. Stimuli were administered to both nostrils. Analysis
      indicated that Parkinson patients were less efficient with the left nostril in
      the matching task, supporting the hypothesis of a larger compromise in the
      nostril contralateral to the side of the body more affected by the disease. Such
      a difference was not observed for the elderly people. Data are discussed with
      reference to the loss of dopamine in Parkinson patients.

PMID- 11453221
TI  - Tactual performance test: item analysis of the memory and location scores.
AB  - An item analytic study of the Tactual Performance Test Memory and Location scores
      was conducted. Item difficulty and Discrimination Index values are presented for
      the total sample and three groups: normal (n = 146), diffusely brain-damaged (n =
      130), and undiagnosed patients sent for assessment (n =326).

PMID- 11453222
TI  - Directed forgetting with global forget instructions in an implicit and explicit
      memory test.
AB  - This study examined differences in directed forgetting effects between an
      implicit and an explicit memory test. 64 students (49 men, 15 women) were
      assigned to 4 (2 x 2) groups. In the middle of the study list, the group was
      given instruction to forget the presented item, whereas the control instruction
      group was not. Half of the subjects were given a Fragment Cued-recall test as an
      explicit memory test, and the other half were given a Fragment Completion test as
      an implicit memory test. Subjects learned an incidental learning task.
      Significant differences were found across conditions for instruction. The
      directed forgetting effect was observed on the explicit memory test (p<.05) but
      not on the implicit memory test. These results are discussed in terms of
      inhibition of retrieval theory.

PMID- 11453223
TI  - The contextual interference effect in acquisition of dart-throwing skill tested
      on a transfer test with extended trials.
AB  - Previous studies of contextual interference have shown that practicing several
      motor skills randomly (high contextual interference) facilitates retention and
      transfer in comparison to practicing the same tasks in a blocked order (low
      contextual interference). However, many studies have not supported this
      phenomenon in motor learning, and some researchers have questioned whether the
      effect can be tested by using only a few trials on the transfer test. The present
      study used a different methodological approach in which the number of test trials
      was increased to assess whether the contextual interference effect is sustained
      over an extended number of trials in the transfer phase. Undergraduate students
      (N=32) were randomly allocated to either a blocked or random group. The
      participants practiced 80 acquisition trials in the dart-throwing task from
      distances of 300 cm and 420 cm, using two different grips. The transfer test
      after a 10-min. interval consisted of 40 trials with a new grip at a distance of
      360 cm. The results did not support the contextual interference effect since
      there were no significant differences between groups on transfer. These findings
      suggest that the contextual interference effect may not be a global learning
      phenomenon which can be generalized to all learning situations.

PMID- 11453224
TI  - Stimulus properties, attentional limitations, and young children's face
      recognition.
AB  - The present research explored 3-, 7-, and 10-yr.-old children's face recognition
      in a "paraphernalia-to-fool" paradigm in which angular size of the stimuli was
      manipulated. It was proposed that, given the attentional limitations of the two
      youngest age groups, facial information and irrelevant paraphernalia would be
      perceived as an undifferentiated whole in stimuli of small visual angles,
      resulting in decreased recognition. However, increasing angular size should
      enable the 7-yr.-olds to differentiate the two types of stimulus information more
      easily. Therefore, it was hypothesized that the influence of paraphernalia on 7
      yr.-olds' performance would be moderated by the spatial size of the stimulus. The
      effect of angular size was also expected to interact with age group. As
      predicted, 10-yr.-olds were unaffected by the size manipulation, 7-yr.-olds'
      performance was moderated by angular size, and, although 3-yr.-olds' recognition
      improved with large stimuli, the increase was not significant. Results are
      discussed in relation to the influence of stimulus properties and age-related
      attentional limitations.

PMID- 11453225
TI  - Assisted ambulation and activities for persons with profound multiple
      disabilities: assessing different ambulation levels.
AB  - Two participants with profound multiple disabilities were exposed to two
      occupational situations, which included 1-min. and 3-min. robot-assisted
      ambulation prior to each activity, respectively. Analysis showed participants'
      mean percentages of engagement time (session time they spent ambulating or
      manipulating objects) were well above 90 in both situations. The amount of
      deviant behavior was somewhat higher in the latter occupational situation for one
      participant. Implications of the findings were discussed.

PMID- 11453226
TI  - An investigation of coaches' perceptions of the causes of home advantage.
AB  - This study investigated the personal experiences of 144 high school coaches in
      terms of their perceptions of the causes of the home advantage. Surveys were
      distributed to varsity coaches of local high school sports asking them to assign
      a percentage value to each of the most common explanations of -the home
      advantage, reflecting the perceived importance of each, e.g., social support,
      travel or fatigue, site familiarity, officials' bias, and self-fulfilling
      prophecy. A 3 x 6 repeated-measures analysis of variance indicated that no
      differences were significant in attribution of the causes of home advantage for
      the combinations of sex of coach and sex of athlete. A significant difference was
      noted in the percentages assigned across the five explanations provided the
      coaches. Post hoc comparison indicated that site familiarity was seen as the most
      important explanation across the combinations of the sex of coach and sex of
      athlete.

PMID- 11453227
TI  - Information retrieval and pedagogy in adapted physical activity.
AB  - The purpose was to address which databases would be most productive for
      literature searches by professionals seeking information on adapted physical
      activity pedagogy. Four databases were searched using 126 pedagogy and 66
      disability terms. The results of the searches (4,130 hits) support the use of
      Sport Discus (n= 2,442 hits) as the most productive database for searches on
      adapted physical activity pedagogy.

PMID- 11453228
TI  - Difference score reliability for tactual performance test trials.
AB  - In further analysis of published data difference score reliabilities are
      presented for the difference between raw score and blocks-per-minute trial scores
      on the Tactual Performance Test.

PMID- 11453229
TI  - Effect of task-relevant cues and state anxiety on motor performance.
AB  - 12 experienced, female trampolinists participated in a field study designed to
      test the conscious processing hypothesis, which predicts that the combination of
      task-relevant knowledge and high state anxiety will impair motor performance.
      Results supported the hypothesis; however, an alternative attentional explanation
      of the data was also identified.

PMID- 11453230
TI  - Implants in regenerated bone in a primate model.
AB  - BACKGROUND: Earlier publications from our laboratory described the use of guided
      bone regeneration to fill large bone voids in the mandible created through en
      bloc resection in primates. The present report describes placement of implants
      into the regenerated bone with subsequent prostheses construction and loading.
      METHODS: Lesions were created in the mandibles of 9 monkeys in a standardized
      mandibular defect of 8 x 19 mm. Reinforced expanded polytetrafluoroethylene
      membranes were placed in the animals and held in place with mini screws and
      sutures for anywhere from 1 to 12 months. No material was added to the defect. In
      each animal a root-form implant was placed 12 mm distal to the abutment teeth
      into the regenerated bone and was loaded with a prosthesis for 12 months. These
      implants were compared to original implants placed in the same monkeys years
      earlier in the same location in non-regenerated bone. Digital radiology and
      histomorphometry are described. RESULTS: The results show that root-form implants
      placed in regenerated bone show the same radiological and histomorphometric
      characteristics as in normal bone when loaded. In addition, the percentage of
      bone contact with implants seen in regenerated bone versus non-regenerated bone
      is the same when both are loaded (65 +/- 13% SD in regenerated bone versus 59 +/-
      15% SD in non-regenerated bone). CONCLUSIONS: In a primate model root-form
      implants placed in regenerated bone and prosthetically loaded show no difference
      when compared to root-form implants placed in non-regenerated bone and
      prosthetically loaded.

PMID- 11453231
TI  - Human gingival fibroblast cytoskeleton is a target for volatile smoke components.
AB  - BACKGROUND: Several in vitro investigations have indicated that the particulate
      phase of cigarette smoke as nicotine affects many cell types including gingival
      fibroblasts, but few studies have examined the effect of volatile fraction on
      cellular structures involved in cell functions such as adhesion and
      proliferation. Since gingival fibroblast survival and reproduction are
      fundamental to maintaining the oral connective tissue as well as to wound
      healing, the effects of acrolein and acetaldehyde, volatile fractions of
      cigarette smoke, on cytoskeleton were examined in human gingival fibroblasts
      (HGFs) in vitro. METHODS: Human gingival fibroblast (HGF) strains from healthy
      subjects with non-inflamed gingiva were utilized. The cells were incubated in
      different concentrations of acrolein and acetaldehyde. Cell adhesion was
      evaluated after 3 hours. The influence of both substances on cytoskeletal
      structures, tubulin and vimentin intermediate filaments (VIF), was investigated
      using indirect immunofluorescence technique. RESULTS: The results show that both
      substances produced similar effects, resulting in a dose-dependent inhibition of
      HGF adhesion. Disturbance of HGF cytoskeleton consisted of a disruption of
      microtubules and vimentin microfilaments with alterations in cell shape.
      CONCLUSIONS: Our experimental findings suggest that volatile fractions of
      cigarette smoke such as acrolein and acetaldehyde, because their ability to bind
      and interact with the cytoskeleton, prevent HGF adhesion. Consequently the
      maintenance of the oral connective tissue and integrity and remodeling could be
      impaired. According to our morphological evidence, these findings confirm other
      clinical and epidemiological investigations reporting that volatile components of
      cigarette smoke could lead to the initiation and progression of periodontal
      disease.

PMID- 11453233
TI  - Prevalence of dehiscences and fenestrations in modern American skulls.
AB  - BACKGROUND: The purpose of this study was to examine the prevalence,
      distribution, and features of alveolar dehiscences and fenestrations in modern
      American skulls and correlate their presence with occlusal attrition, root
      prominence, and alveolar bone thickness. METHODS: A representative sample of 146
      dentate modern American skulls from a collection at the National Museum of
      Natural History were examined. RESULTS: The skulls were from subjects ranging in
      age from 17 to 87 years old (mean 49.1 years). The mean number of teeth per skull
      was 22.7 and the mean number of either dehiscence or fenestration defects per
      skull was 3.0. Of the 3,315 individual teeth examined, 4.1% (135) had dehiscences
      and 9.0% (298) had fenestrations. A dehiscence was present in 40.4% of the
      skulls, and a fenestration was present in 61.6% of skulls. Mandibular canines
      were most often affected by dehiscences (12.9%), while maxillary first molars
      were most often affected by fenestrations (37.0%). Sixty-seven percent of
      dehiscences were found in the mandible, and 58% of fenestrations were found in
      the maxilla. CONCLUSIONS: The presence of dehiscences and fenestrations were
      positively correlated with thin alveolar bone and negatively correlated with
      occlusal attrition. African-American males and Caucasian females were
      significantly more likely to have dehiscences, while African-American females
      were significantly more likely to have fenestrations.

PMID- 11453232
TI  - Effects of dipeptide bestatin on Porphyromonas gingivalis and epithelial cells.
AB  - BACKGROUND: Dipeptide bestatin has been previously reported to selectively
      inhibit the growth of Porphyromonas gingivalis. The aims of this study were to
      investigate the mechanism of action of bestatin and to evaluate its effect on
      epithelial cells. METHODS: The inhibitory effect of bestatin on P. gingivalis was
      tested in vitro (culture medium) and in vivo (guinea pig model). Radiolabeled
      compounds were used to investigate the effect of bestatin on the uptake of amino
      acids and peptides. The cytotoxic effect of bestatin was evaluated using a
      keratinocyte cell line. RESULTS: The growth inhibition of P. gingivalis by
      bestatin was concentration-dependent. Even at high concentrations, compounds
      possessing a chemical structure or an aminopeptidase inhibitor activity related
      to bestatin had no effect on growth of P. gingivalis. When injected in the
      presence of P. gingivalis, bestatin was able to prevent the development of a
      necrotic abscess in a guinea pig model. Data were obtained suggesting that
      bestatin does not act on proteinases of P. gingivalis. Rather, bestatin was found
      to inhibit the intracellular uptake of radioactivity from 14C-labeled amino acids
      or heat-denatured type I collagen. This was not observed with a spontaneous
      mutant of P. gingivalis, whose growth was not affected by bestatin. In the second
      part of the study, bestatin was found to have no effect on epithelial cell
      viability in culture at concentrations effective on P. gingivalis. In addition,
      bestatin did not show effects on epithelial cell migration or production of
      gelatinases. CONCLUSIONS: This study suggests that bestatin selectively inhibits
      growth of P. gingivalis by affecting the intracellular uptake of amino acids and
      peptides, which serve as energy and nitrogen sources for this bacterial species.
      Bestatin has no cytotoxicity and may represent a therapeutic molecule for local
      treatment of P. gingivalis-associated periodontitis.

PMID- 11453234
TI  - Effects of pretreatment clinical parameters on bioactive glass implantation in
      intrabony periodontal defects.
AB  - BACKGROUND: The various methods for regeneration of periodontal tissue that have
      been developed can be classified into guided tissue regeneration and bone
      implantation. Since the implantation materials have shown both deficiencies and
      merits, dentists have begun exploring the bioactive glass first used in plastic
      surgery. This paper examines the effectiveness of this new material on
      periodontal intrabony defects. METHODS: Clinical effects of bioactive glass
      implantation in intrabony periodontal defects were evaluated 6 months after
      surgery in 38 intrabony defects from 38 patients with chronic periodontitis.
      Twenty-one experimental defects received bioactive glass implantation (test
      group), while 17 control defects were treated with a flap procedure only (control
      group). The criteria for comparative observation were preoperative and
      postoperative probing depth (PD), clinical attachment level (CAL), bone probing
      depth (BPD), and gingival recession. RESULTS: Reductions in PD were observed in
      both groups (P<0.01). The reduction in PD was significantly greater in the test
      group when preoperative PD exceeded 7 mm (P<0.01). Improvements in CAL were also
      observed in both groups (P<0.01), with the test group showing significantly
      greater gains (P<0.05). In those cases where preoperative CAL was less than 7 mm,
      there was no statistically significant difference between the two groups.
      Reduction in BPD was observed in both groups, with the test group showing
      significantly greater reduction (P <0.01). There was no significant difference in
      BPD change, however, when preoperative BPD was < or =7 mm. Significantly greater
      reduction of BPD in the test group was observed when intrabony defect depth was
      >4 mm (P <0.05). Significant improvements in PD, CAL, and BPD were noted in the
      test group when the crestal involvement exceeded 100 degrees. Correlation test
      between various clinical parameters indicated that greater changes in PD and CAL
      in the test group were observed when preoperative CAL was large (P<0.001), and
      greater changes in PD (P<0.05), CAL (P<0.01), and BPD (P<0.05) were noted when
      preoperative BPD was large. Correlation between crestal involvement and CAL
      change was noted only in the control group (P<0.01). High correlations were
      observed between PD changes and CAL changes and between CAL changes and BPD
      changes in both groups. CONCLUSIONS: Use of a bone substitute in a flap operation
      resulted in significantly greater improvements in CAL and BPD over flap operation
      alone and seemed to have positive effects in postoperative PD, CAL, and BPD in
      those cases with more severe preoperative CAL and BPD.

PMID- 11453235
TI  - Human papillomavirus infection in cyclosporin-induced gingival overgrowth in
      renal allograft recipients.
AB  - BACKGROUND: Host immunity plays an important role in the development of human
      papillomavirus (HPV)-associated disease. The HPV infection in oral cyclosporin
      induced gingival overgrowth in renal transplant recipients has not been
      investigated previously. The aim of this study was to establish the HPV infection
      of cyclosporin-induced gingival hyperplasia in renal transplant recipients
      through morphological changes and use of the in situ hybridization technique.
      METHODS: We examined 13 renal transplant recipient biopsies with gingival
      overgrowth lesions and 4 healthy mucosa samples of these patients. The
      histopathological diagnoses were established on the basis of widely accepted
      criteria, and the pathologist was not aware of the HPV result. An in situ
      molecular hybridization was carried out under low stringent conditions to detect
      HPV species with mixed biotin-labeled probes of HPV 6 and HPV 11, and under high
      stringent conditions with HPV 6, HPV 11, HPV 16, and HPV 18 probes for HPV
      typing. RESULTS: The HPV prevalence among the 13 samples studied was 92.31%
      (12/13), of which 4 tested positive for HPV 6-11 and 1 for HPV 16. The 4 biopsies
      of normal mucosa from gingival overgrowth patients were also reactive for HPV
      DNA. In 11/12 (91.7%) HPV-positive cases, koilocytotic atypia was found.
      CONCLUSIONS: The suppression of T-cell function by cyclosporin therapy can result
      in an increase of HPV infection, adding to the proliferative activity of
      cyclosporin in the oral mucosa.

PMID- 11453236
TI  - Upregulation of keratinocyte growth factor in cyclosporin A-induced gingival
      overgrowth.
AB  - BACKGROUND: Drug-induced gingival overgrowth (GO) is a frequent and adverse side
      effect associated principally with the administration of the immunosuppressive
      drug cyclosporin A (CsA) and also certain anti-epileptic and anti-hypertensive
      drugs. It is characterized by a marked increase in the thickness of the
      epithelial layer and the accumulation of excessive amounts of connective tissue.
      Although the mechanism by which the drugs cause GO is not yet understood,
      keratinocyte growth factor (KGF), which is a potent epithelial cell mitogen, has
      been implicated in other hyperplastic conditions, including mammary and prostatic
      hyperplasia, and could also be involved in the molecular pathology of GO.
      METHODS: Immunohistochemistry was used to examine the expression of KGF in normal
      gingiva (NG) and GO tissue sections. The relative level of KGF mRNA in GO tissue
      and cells was compared with that of NG tissue and fibroblast cells using the semi
      quantitative reverse transcribed-polymerase chain reaction (RT-PCR) and DNA
      sequencing was carried out to confirm the identity of the PCR product. RESULTS:
      KGF antigen and mRNA were readily detected in the GO tissue immunohistochemically
      and by RT-PCR, respectively, but were not expressed in the NG tissue. Moreover,
      KGF transcripts were found to be approximately 2 times higher in the GO than in
      the NG fibroblasts in vitro, although the difference was not statistically
      significant. CONCLUSIONS: This study has shown, for the first time, that the
      level of KGF is elevated in GO and suggests that KGF may have an important role
      in the enhanced epithelial proliferation associated with GO.

PMID- 11453237
TI  - In vitro comparison of bioabsorbable and non-resorbable membranes in bone
      regeneration.
AB  - BACKGROUND: Barrier membranes are used to prevent down-growth of the oral mucosa
      along the root surface and to allow alveolar bone regeneration in guided tissue
      regeneration. Several studies have demonstrated bone regenerates in the presence
      of bioabsorbable and non-resorbable membranes, but no studies have compared
      multiple bioabsorbable barriers to one another and to non-resorbable barriers.
      This study evaluated the in vitro influence of bioabsorbable and non-resorbable
      membranes on specific parameters of human osteoblast activity. METHODS: Human
      osteoblasts were cultured on bioabsorbable membranes made of collagen, hyaluronic
      acid, and poly DL-lactide, and the most common non-resorbable membrane which is
      made of expanded polytetrafluoroethylene (ePTFE). The osteoblasts were cultured
      in vitro for 24 hours on barrier membranes in the presence of 3H-thymidine and 3H
      proline to study cell proliferation and collagen synthesis. Transforming growth
      factor-beta1 (TGF-beta1) secretion was evaluated in conditioned media using an
      ELISA kit. RESULTS: The results showed that collagen and poly DL-lactide
      stimulated DNA synthesis more than ePTFE and hyaluronic acid. All bioabsorbable
      membranes significantly increased collagen synthesis and alkaline phosphatase
      activity. Collagen and hyaluronic acid increased secretion of TGF-beta1, a growth
      factor involved in bone remodeling. CONCLUSIONS: These data suggest bioabsorbable
      membranes, particularly collagen and hyaluronic acid, may promote bone
      regeneration through their activity on osteoblasts.

PMID- 11453238
TI  - Coronally advanced flap procedure: is the interdental papilla a prognostic factor
      for root coverage?
AB  - BACKGROUND: This study was designed to verify if the dimension of the interdental
      papilla may be a prognostic factor for the clinical outcome of the coronally
      advanced flap (CAF) in the treatment of gingival recessions. METHODS: Thirty
      three Miller Class I recessions were treated in 33 patients using the CAF
      procedure. Two types of measurements were performed: 1) clinical measurements
      (probing depth, recession depth, width of keratinized tissue, clinical attachment
      level) were recorded at baseline and 3 months after surgery and 2) all recessions
      were photographed and transformed into computer images. A specific software
      allowed recording of both linear and square measurements. The following digital
      measurements were recorded at baseline: 1) base, height, and area of the mesial
      and distal papillae adjacent to the involved tooth and 2) width/depth of the
      recession and the area of the exposed root surface of the involved tooth. The
      residual recession area, if any, was recorded 3 months after surgery. The digital
      measurements of the height and of the area of the papilla were used in
      statistical analysis (multiple linear regression and logistic regression) to
      evaluate a possible correlation with root coverage (mm2) and/or with complete
      root coverage. RESULTS: Root coverage was not significantly correlated to the
      papilla area (P= 0.3692) or to papilla height (P= 0.0968). The complete root
      coverage was not correlated to the papilla area (P= 0.3181), but it was
      correlated to papilla height (P= 0.0499). CONCLUSIONS: This study indicates that
      the root coverage following CAF procedure is not significantly correlated to
      papilla dimension. However, complete root coverage is significantly more frequent
      in sites with lower height of the adjacent papilla.

PMID- 11453239
TI  - Retrospective evaluation of the influence of the interleukin-1 genotype on
      radiographic bone levels in treated periodontal patients over 10 years.
AB  - BACKGROUND: A difference in genetic susceptibility to plaque accumulation has
      been advocated to explain different responses to periodontal therapy. The purpose
      of this study is to assess the role of the interleukin-1 (IL-1) polymorphism on
      the rate of bone and tooth loss in non-smoking periodontally treated patients
      during maintenance. METHODS: Sixty consecutive non-smoking patients (mean age
      46.8 +/- 5.0) with moderate to severe periodontitis, treated and maintained for
      over 10 years were selected. At baseline (T0), radiographic evaluation (cemento
      enamel junction [CEJ]-root apex, CEJ-bottom of defect mesial and distal, CEJ-bone
      crest mesial and distal, crown-root ratio) was performed. All patients received
      scaling and root planing; 36 patients then underwent surgical therapy.
      Subsequently, all patients were enrolled in a periodontal maintenance program
      with recall visits every 3.4 +/- 1.0 months for at least 10 years. At the latest
      recall visit (T2) the same radiographic measurements evaluated at baseline were
      taken and a DNA sample for IL-1 genetic susceptibility testing was collected and
      sent for analysis. RESULTS: Twenty-three of the 60 patients (38.3%) were IL-1
      genotype positive. A total of 52 teeth (3.3%) out of 1,566 were lost due to
      periodontitis between T0 and T2; 28 of 957 (2.9%) in the IL-1 genotype negative
      group and 24 of 609 (3.9%) in IL-1 genotype positive group. The mean variation in
      bone defect level (DeltaBD) averaged -0.04 mm in IL-1 genotype negative patients
      and 0.01 mm in IL-1 genotype positive patients. The mean variation in bone crest
      level (DeltaBC) averaged -0.24 mm in IL-1 genotype negative patients and -0.28 mm
      in IL-1 genotype positive patients. However, a few patients showed significant
      differences in response to therapy based on initial bone levels and genotype. IL
      1 negative patients who showed minimal initial bone loss responded to the therapy
      better than the IL-1 positive patients. IL-1 positive patients with severe
      initial bone loss showed a better response to the therapy than IL-1 negative
      patients. CONCLUSIONS: On average, there were no significant differences related
      to IL-1 genotype in tooth loss after 10 years in a non-smoking, well-maintained
      periodontal population. On an individual patient basis, the IL-1 genotype, in
      combination with the initial bone level, seems useful at the beginning of therapy
      for predicting bone level variation.

PMID- 11453240
TI  - The effect of antimicrobial periodontal treatment on circulating tumor necrosis
      factor-alpha and glycated hemoglobin level in patients with type 2 diabetes.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) may play an important role in
      insulin resistance. In this study, we hypothesized that TNF-alpha produced due to
      periodontal inflammation synergistically affects insulin resistance as well as
      TNF-alpha produced from adipose tissues in insulin-resistant type 2 diabetes
      patients. Therefore, to understand the effects of antimicrobial periodontal
      therapy on serum TNF-alpha concentration and subsequent metabolic control of
      diabetes, we examined the periodontal and diabetic status on 13 type-2 diabetes
      patients. METHODS: These patients were treated with local minocycline
      administration in every periodontal pocket around all existing teeth once a week
      for a month. Before and after treatment, the number of total bacteria in the
      periodontal pockets and circulating TNF-alpha concentration were measured and the
      HbA1c value was assessed. RESULTS: Antimicrobial therapy significantly reduced
      the number of microorganisms in periodontal pockets (P <0.01). After treatment,
      the circulating TNF-alpha level was significantly reduced (P <0.015). The HbA1c
      value was also reduced significantly (P <0.007). In addition, the 6 patients who
      were not receiving insulin therapy demonstrated decreased fasting insulin levels
      (P <0.03), and HOMA-R (P <0.03) indices. The average reductions in circulating
      TNF-alpha concentration and HbA1c value were 0.49 pg/ml and 0.8%, respectively.
      CONCLUSION: The results indicate that anti-infectious treatment is effective in
      improving metabolic control in diabetics, possibly through reduced serum TNF
      alpha and improved insulin resistance.

PMID- 11453241
TI  - Relationship between rheumatoid arthritis and periodontitis.
AB  - BACKGROUND: Because of several similar features in the pathobiology of
      periodontitis and rheumatoid arthritis, in a previous study we proposed a
      possible relationship between the two diseases. Therefore, the aims of this study
      were to study a population of rheumatoid arthritis patients and determine the
      extent of their periodontal disease and correlate this with various indicators of
      rheumatoid arthritis. METHODS: Sixty-five consecutive patients attending a
      rheumatology clinic were examined for their levels of periodontitis and
      rheumatoid arthritis. A control group consisted of age- and gender-matched
      individuals without rheumatoid arthritis. Specific measures for periodontitis
      included probing depths, attachment loss, bleeding scores, plaque scores, and
      radiographic bone loss scores. Measures of rheumatoid arthritis included tender
      joint analysis, swollen joint analysis, pain index, physician's global assessment
      on a visual analogue scale, health assessment questionnaire, levels of C-reactive
      protein, and erythrocyte sedimentation rate. The relationship between periodontal
      bone loss and rheumatological findings as well as the relationship between bone
      loss in the rheumatoid arthritis and control groups were analyzed. RESULTS: No
      differences were noted for the plaque and bleeding indices between the control
      and rheumatoid arthritis groups. The rheumatoid arthritis group did, however,
      have more missing teeth than the control group and a higher percentage of these
      subjects had deeper pocketing. When the percentage of bone loss was compared with
      various indicators of rheumatoid arthritis disease activity, it was found that
      swollen joints, health assessment questionnaire scores, levels of C-reactive
      protein, and erythrocyte sedimentation rate were the principal parameters which
      could be associated with periodontal bone loss. CONCLUSIONS: The results of this
      study provide further evidence of a significant association between periodontitis
      and rheumatoid arthritis. This association may be a reflection of a common
      underlying disregulation of the inflammatory response in these individuals.

PMID- 11453242
TI  - The dento-epithelial junction: cell adhesion by type I hemidesmosomes in the
      absence of a true basal lamina.
AB  - BACKGROUND: The junctional epithelium (JE) is a unique structure that makes
      contact with both a non-renewable hard tooth surface and with a basement membrane
      (BM) facing the connective tissue. Ultrastructurally, this attachment occurs
      through hemidesmosomes (HD) and a basal lamina-like extracellular matrix which,
      on the tooth side, is termed the internal basal lamina. In this study we
      investigated the expression of basal cell markers in the tooth-facing (TF) cells
      of JE. METHODS: Samples of healthy marginal gingiva were removed by careful
      dissection. The expression of laminin-5 was used to indicate TF cell preservation
      in double immunofluorescence labeling and confocal laser scanning microscopy.
      RESULTS: The results show that integrin alpha6beta4 and laminin-5 colocalize
      unequivocally in the TF cells. The results also show the specific expression of
      the basal cytokeratin 14 and the alpha(v) integrin subunit in the TF cells. All 3
      major hemidesmosomal components BP180, BP230, and HD1 antigen are likewise
      present. On the other hand, type IV collagen, laminin-1/10, type VII collagen,
      and the BM proteoglycan perlecan are all absent from the dento-epithelial
      junction. CONCLUSIONS: The results indicate that the epithelium-tooth interface
      is a unique structure wherein epithelial cells adhere by means of bona fide
      hemidesmosomes to an epithelium-derived extracellular matrix lacking most of the
      common BM components. Moreover, TF cells differ from connective tissue facing
      (CTF) cells, not only by their cell surface molecules and their production of
      extracellular matrix, but also by their cytoskeletal architecture.

PMID- 11453243
TI  - Gingival, dermal, and periodontal ligament fibroblasts express different
      extracellular matrix receptors.
AB  - BACKGROUND: Fibroblasts are the predominant cells of the periodontal ligament and
      the gingiva and have important roles in the function and regeneration of the
      tooth support apparatus. The goal of this study was to investigate the possible
      differences in the adhesion properties and expression of extracellular matrix
      (ECM) receptors among different fibroblast populations. METHODS: The adhesion of
      gingival (GF), dermal (DF), and periodontal ligament fibroblast (PDLF) cultures
      to ECM proteins (fibronectin, laminin, vitronectin, RGD peptide, collagen type I,
      and collagen type IV) adsorbed to tissue culture plastic was evaluated
      fluorometrically. Quantitative reverse transcription-polymerase chain reactions
      (RT-PCR) were performed using primers specific for 19 integrin subunits to
      quantify ECM receptor transcript expression. RESULTS: Our data demonstrated that
      GF and PDLF adhere to vitronectin and collagen types I and IV more avidly than do
      DF. PDLF adhered well to laminin, whereas GF and DF did not. Quantitation of
      integrin expression demonstrated that the different fibroblast types expressed
      different integrin transcripts, further demonstrating their innate differences.
      CONCLUSIONS: The 3 fibroblast types studied behave differently and expressed
      different ECM receptors. However, gingival fibroblasts and periodontal ligament
      fibroblasts are more similar in their attachment and integrin expression than
      either is to dermal fibroblasts. Therefore, experiments using DF will not
      necessarily be valid for oral tissues.

PMID- 11453244
TI  - The influence of transforming growth factor-beta1 gene polymorphisms on the
      severity of gingival overgrowth associated with concomitant use of cyclosporin A
      and a calcium channel blocker.
AB  - BACKGROUND: The purpose of this study was to determine whether the prevalence and
      severity of gingival overgrowth in renal transplant recipients concomitantly
      treated with cyclosporin and a calcium channel blocker was associated with
      functional polymorphisms within the signal sequence of the transforming growth
      factor-(TGF)beta1 gene. METHODS: The extent and severity of gingival overgrowth
      for 164 renal transplant recipients immunosuppressed with cyclosporin A and
      concomitantly taking a calcium channel blocker since transplant were entered into
      the study (86 in Manchester, 78 in Belfast). Two biallelic polymorphisms of the
      TGF-beta1 gene were studied at position +869, codon 10 (leucine to proline
      substitution), and position +915, codon 25 (arginine to proline substitution).
      RESULTS: Subjects who were homozygous for proline at codon 10 had significantly
      higher overgrowth scores than those who were heterozygous (P= 0.03) or homozygous
      for leucine (P= 0.01). Subjects who were heterozygous (arginine/proline) at codon
      25 had a significantly higher (P= 0.04) gingival overgrowth score than those who
      were homozygous for arginine. Logistic regression analysis indicated that for
      codon 25 independent predictors of severe gingival overgrowth were the
      heterozygous arginine/proline genotype (P= 0.009) and whether the individual was
      young (P= 0.05). CONCLUSIONS: Polymorphisms in the TGF-beta1 gene influence the
      expression of gingival overgrowth in renal transplant recipients concomitantly
      treated with cyclosporin and a calcium channel blocker. The polymorphism in the
      TGF-beta1 gene at codon 25 represented an independent genetic determinant of
      severe gingival overgrowth in the susceptible subjects studied.

PMID- 11453246
TI  - Successful periodontal maintenance of a case with Papillon-Lefevre syndrome: 12
      year follow-up and review of the literature.
AB  - BACKGROUND: Various approaches to treating the periodontal condition associated
      with Papillon-Lefevre syndrome have been reported. These include oral hygiene
      instruction, use of mouthrinses, frequent debridement, multiple antibiotic
      regimens, periodontal surgery, extraction of hopeless teeth, and extraction of
      all deciduous teeth. Because Papillon-Lefevre syndrome is rare, most publications
      are case reports, and very few document long-term successful treatment of the
      periodontal condition. METHODS: In 1986, a 3.5-year-old Indo-Canadian male was
      diagnosed with Papillon-Lefevre syndrome and began periodontal treatment. Initial
      therapy consisted of debridement every 3 weeks, a 0.12% chlorhexidine mouthrinse,
      2 regimens of metronidazole, and oral hygiene instruction for his parents. After
      10 months it became apparent that the treatment was having little beneficial
      effect, since the periodontal destruction continued and teeth 51 and 61
      exfoliated. At age 4, all remaining deciduous teeth were extracted and complete
      dentures inserted for the following 2-year edentulous period; then a 3-month
      maintenance schedule was maintained. RESULTS: The patient is now 17 years old and
      all his adult teeth are present with the exception of the third molars. His oral
      hygiene varies between moderate and good, with his most recent plaque score at
      80% effectiveness. There are no probing depths greater than 4 mm, with the
      exception of the distal of the lower second molars where opercula are present.
      CONCLUSIONS: Extraction of all the deciduous teeth followed by a period of
      edentulousness may partially explain the fact that there has been no recurrent
      attachment loss in the permanent teeth up to age 17. Other explanations are
      discussed as part of the literature review of Papillon-Lefevre syndrome.

PMID- 11453245
TI  - Platelet-derived growth factor (PDGF) gene delivery for application in
      periodontal tissue engineering.
AB  - BACKGROUND: A challenge in the reconstruction of periodontal structures is the
      targeted delivery of growth-promoting molecules to the tooth root surface.
      Polypeptide growth factors such as platelet-derived growth factor (PDGF)
      stimulate both cementogenesis and osteogenesis. Recent advances in gene therapy
      offer the advantage of delivering recombinant proteins to tissues for extended
      periods of time in vivo. METHODS: Recombinant adenoviral vectors encoding for the
      PDGF-A gene were constructed to allow delivery of PDGF transgenes to cells. The
      recombinant adenoviruses were assembled using the viral backbone of Ad2/CMV/EGFP
      and replacing GFP (reporter gene encoding green fluorescent protein driven by the
      cytomegalovirus promoter [CMV] within adenovirus type 2) with the PDGF-A gene.
      Root lining cells (cloned cementoblasts) were transduced with Ad2/PDGF-A and
      evaluated for gene expression, DNA synthesis, and cell proliferation. PDGF
      inducible genes, c-myc and osteopontin, were also evaluated following gene
      delivery of Ad2/PDGF-A. RESULTS: The results revealed high level transduction of
      cementoblasts by gene transfer for 7 days as evidenced by flow cytometry and
      Northern blotting. Cementoblast DNA synthesis and subsequent proliferation were
      stimulated by Ad2/PDGF-A at levels equal to or greater than continuous rhPDGF-AA
      application. Strong message for the PDGF-A gene and protein as evidenced by
      Northern blotting and immunocytochemistry was noted. Furthermore, the potent
      induction of c-myc and osteopontin mRNA was found after PDGF gene delivery to
      cementoblasts. CONCLUSIONS: These findings demonstrate that gene delivery of
      platelet-derived growth factor stimulates cementoblast activity that is sustained
      above that of rhPDGF-AA application. The use of gene therapy as a mode of growth
      factor delivery offers a novel approach to periodontal tissue engineering.

PMID- 11453247
TI  - Metal piercing through the tongue and localized loss of attachment: a case
      report.
AB  - The piercing of intraoral structures to accommodate different types of jewelry
      has increased in popularity in the last few years. The association of an
      intraoral piercing with localized periodontitis is not well documented in the
      literature. A 22-year-old male presented to our clinic with a tongue stud placed
      through the mid-dorsum of his tongue. The inferior sphere was coated with plaque
      and calculus. Teeth #24 and #25 exhibited 6 mm interproximal probing depth and
      recession, horizontal radiographic bone loss, and tissue indentations consistent
      with the shape of the inferior ball of the tongue stud directly on the lingual
      surfaces of both teeth. The treatment consisted of an adult prophylaxis, flap
      curettage of the mandibular anterior region, oral hygiene instructions, and
      removal of the tongue stud. At our follow-up visit, the patient's oral hygiene
      had improved, he has removed the jewelry, and the attachment loss appears to have
      stabilized.

PMID- 11453248
TI  - Tissue banking of bone allografts used in periodontal regeneration.
AB  - This paper was prepared by the Committee on Research, Science and Therapy of the
      American Academy of Periodontology for the information of the dental profession.
      However, it may also be of interest to the lay public. It represents the position
      of the American Academy of Periodontology regarding tissue banking and the use of
      bone allografts in periodontal therapy.

PMID- 11453249
TI  - The Schizosaccharomyces pombe Cdc42p GTPase signals through Pak2p and the Mkh1p
      Pek1p-Spm1p MAP kinase pathway.
AB  - The Cdc42p GTPase is involved in many aspects of growth and cell-cycle
      regulation, including actin cytoskeletal rearrangements and activation of signal
      transduction pathways. To further investigate these functions, genetic
      interactions were examined between Schizosaccharomyces pombe Cdc42p, its
      effectors Pak1p and Pak2p, and the Mkh1p-Pek1p-Spm1p signal transduction pathway,
      which functions in cytokinesis and cell division. Expression of a truncated
      version of Pak2p lacking its N-terminal autoinhibitory domain led to a growth
      defect that was suppressed by deltamkh1 and deltaspm1 null mutations and an
      elongated cell phenotype indicative of a cell division defect that was suppressed
      by the deltamkh1 mutation. In addition, expression of the constitutively
      activated cdc42G12V mutant allele led to a growth defect that was rescued by the
      deltapak2 and deltamkh1 mutations. The deltapak2 mutation did not suppress the
      growth defect conferred by plasmid expression of Mkh1p, suggesting that Pak2p
      functions upstream of Mkh1p in this pathway. A two-hybrid protein interaction was
      observed between Pak2p and Mkh1p, but not between Pak1p and Mkh1p. These results
      are consistent with Cdc42p interacting with Pak2p to signal through the Mkh1p
      Pek1p-Spm1p pathway.

PMID- 11453250
TI  - Functional analysis of RNA polymerase II Rpb3 mutants of the fission yeast
      Schizosaccharomyces pombe.
AB  - The RNA polymerase II (Pol II) of Schizosaccharomyces pombe is composed of 12
      subunits. Subunit Rpb3 has sequence homology with the N-terminal domain of the
      prokaryotic alpha subunit, which plays a key role in RNA polymerase assembly.
      Together with the Rpb2 (the beta homologue) and Rpb11 (the second alpha
      homologue) subunits, Rpb3 constitutes a core subassembly (Rpb2-Rpb3-Rpb11) which
      corresponds to the the alpha2beta assembly intermediate of prokaryotic RNA
      polymerase. For the functional mapping of Rpb3, we made a collection of 12 heat
      sensitive (Ts) or cold-sensitive (Cs) S. pombe mutants, each carrying a single
      mutation in one of the four conserved regions of Rpb3. The altered functions of
      six representative Pol II mutants containing the mutant Rpb3 were analyzed in
      vitro using an improved version of the GAL4-VP16 activator-dependent
      transcription system catalyzed by S. pombe cell extracts. The transcription
      activity by the extracts from Rpb3 mutants decreased to varying extents after
      heat treatment; but the extracts from Rpb3 mutants which had mutations in the
      eukaryote-specific conserved regions B and C regained their activity by the
      addition of GAL4-VP16, to a larger extent than those from the region A and D
      mutants. We propose that both terminal regions (A and D) play important roles in
      RNA polymerase assembly, while the central portion (regions B and C) is involved
      in activated transcription.

PMID- 11453251
TI  - Factors involved in the regulation of the Schizosaccharomyces pombe malic enzyme
      gene.
AB  - Transcription of the Schizosaccharomyces pombe malic enzyme gene, mae2, is
      induced when cells are grown on high glucose concentrations or under nonaerated
      conditions. Two cis-acting elements in the mae2 promoter, upstream activator
      sequences UAS1 and UAS2, are required for basal expression, whilst three negative
      acting, upstream repressor sequences are involved in general derepression of
      mae2. Both the Pka1 and Sty1 signal transduction pathways are involved in the
      induced expression of mae2 under fermentative conditions. Expression of mae2
      seems to be regulated in response to the carbon source, lack of oxygen and
      osmotic stress conditions, probably to assist in maintaining the intracellular
      redox balance.

PMID- 11453252
TI  - Intrachromosomal recombination after targeted monocopy integration in Penicillium
      chrysogenum: stabilization of the direct repeats to prevent loss of the inserted
      gene.
AB  - Monocopy systems obtained by targeted integration at the pyrG locus of P.
      chrysogenum led to the formation of unstable direct repeats in the genome. A
      previously isolated pyrG mutant was sequenced and the mutation was found to be
      located at nucleotide position 665 of the pyrG gene. A different pyrG mutation
      was introduced in vitro at the BamHI site of this gene. Recombination products
      arising from monocopy systems using the bleomycin/phleomycin resistance gene
      (ble) as a model were studied to elucidate the intrachromosomal recombination
      mechanisms. Experimental results showed that both gene conversion and deletion
      events occurred spontaneously at the integration site. Gene conversion products
      were obtained at a frequency of one in 3.4x10(4) viable transformant spores. When
      gene conversion occurred, the inserted exogenous gene was retained and was
      flanked by rearranged direct repeats of the pyrG gene, each containing at least
      one pyrG mutation. Deletion events resulted in the loss at high frequency of the
      inserted exogenous gene. Genetic stabilization of a monocopy system was obtained
      when both pyrG repeats (formed at the targeted integration site) contained at
      least one identical mutation, since in this case further recombinations can be
      easily counter-selected.

PMID- 11453253
TI  - The IsdA gene is necessary for sexual development inhibition by a salt in
      Aspergillus nidulans.
AB  - Using one of 17 expressed sequence tags (ESTs) previously identified as specific
      to the late sexual developmental (LSD) stage of Aspergillus nidulans, a gene for
      the subject EST was isolated. The determined DNA sequences revealed an open
      reading frame encoding a 356 amino acid polypeptide which does not share a
      sequence similarity to previously identified genes or proteins. The isolated gene
      was named lsdA (late sexual development), since it was expressed abundantly at
      the LSD stage. The lsdA gene expression began earlier than at the LSD stage.
      Disruption of the lsdA gene in the veA+ background strongly induced sexual
      development under conditions where sexual development in wild-type strains is
      almost completely inhibited. In contrast, in the veA1 background, an lsdA null
      mutant failed to show any phenotypic difference in sexual development under the
      various conditions tested. These results indicate that the lsdA gene may be
      responsible for inhibiting the sexual development of veA+ strains by a high
      concentration of a salt.

PMID- 11453254
TI  - Identification and characterization of a gene encoding a subtilisin-like serine
      protease induced during the vegetative incompatibility reaction in Podospora
      anserina.
AB  - In the filamentous fungi, cell fusion between unlike individuals generally
      triggers a cell-death reaction known as vegetative incompatibility. In Podospora
      anserina, it was shown that, during this cell-death reaction, there is a strong
      increase in proteolytic activity. Here, we report the purification of a 36-kDa
      protease that is induced during the incompatibility reaction. An internal peptide
      of this protein displayed a strong similarity with the PEPC subtilisin-like
      serine protease from Aspergillus niger. This led us to use the pepC gene as a
      probe to clone the homologous gene from P. anserina, which we called pspA. The
      expression of pspA is upregulated at the transcript level during the progress of
      the incompatibility reaction. This induction is diminished in strains bearing
      suppressors of the vegetative incompatibility reaction. The fact that pspA is
      homologous to PrB, a vacuolar protease involved in autophagy in yeast, suggests
      that the incompatibility cell-death reaction and autophagy might be related
      processes.

PMID- 11453255
TI  - The beta-tubulin-encoding gene from Microbotryum violaceum: unusual in a variety
      of ways.
AB  - The beta-tubulin gene of Microbotryum violaceum was sought originally for its
      potential use in improving the transformation of this organism. The gene was
      cloned and its nucleotide sequence was determined. The gene was predicted to
      encode a 444-residue protein with strong sequence similarity to other beta
      tubulins. The coding region was 2.85 kb, much larger than the corresponding genes
      from other organisms. This was due to the large number of introns in this gene,
      as determined by comparison of the cDNA sequence with that for the genomic clone.
      This gene contained 14 introns, which is the most introns in a beta-tubulin
      encoding gene yet reported for any organism. Intron position comparisons between
      the M. violaceum gene and those from beta-tubulin genes of other organisms
      revealed a striking result, since 10 of the 14 introns were unique. An additional
      feature of the gene's organization was an unusually long 5' untranslated region,
      predicted to be nearly 1 kb in length. The possible significance of these unusual
      features of genetic structure is discussed.

PMID- 11453256
TI  - Truncated and dispersed rpl2 and rps19 pseudogenes are co-transcribed with
      neighbouring downstream genes in wheat mitochondria.
AB  - The wheat mitochondrial genome contains only partial coding sequences for the L2
      and S19 ribosomal proteins, unlike in rice or liverwort mitochondria, where these
      genes are functional and have a bacterial-type linkage. A single-copy stretch
      corresponding to the extreme 3' terminus of the wheat rpl2 gene is co-transcribed
      with the trans-splicing nad1 exon 4; and, at another unique location, the rps19
      segment lacking the 5' coding region is co-transcribed with the downstream nad4L
      gene. In both cases, the 5' termini of these transcripts map to promoter
      consensus motifs acquired through genomic reorganization, enabling continued
      expression of essential downstream genes. In both wheat and rice, the rpl2 and
      rps19 genomic regions differ in their RNA profiles between germinating embryos
      and seedlings. The absence of intact rpl2 and rps19 genes in wheat mitochondria
      is consistent with their inactivation through DNA rearrangement/deletion after
      the successful transfer of functional copies to the nucleus.

PMID- 11453257
TI  - Going home: giving voice to memory strategies of young Mayan refugees who
      returned to Guatemala as a community.
AB  - Around 1982, thousands of Guatemalan Mayas fled their villages and lands to
      escape the Rios Montt scorched-earth policy implemented in rural areas. After
      more than a decade of exile, many of those refugees have returned to their
      homeland. This paper looks at the ways in which young Mayan refugees who have
      returned home after extended exile in Mexico appropriate and distance themselves
      from the collective project of going home. Two Mayan communities of retornados
      (returnees), whose paths into exile and home again differ slightly, are compared.
      Outside support from international organizations and cohesion in the refugee
      camps enabled the young people of La Victoria to see disclosure of the traumatic
      past from a position of strength and confrontation as the key to social change.
      In La Esperanza, the past is rebuilt by the youth around avoidance of recent
      history, and tradition appears as a bridge between past and future. The way the
      youth of the two communities construct their homecoming demonstrates how small
      changes in the migration experience may result in considerable differences in the
      choice of strategies, and raises important questions about assistance programs
      that might be developed for these populations.

PMID- 11453258
TI  - Dynamics of inclusion and exclusion: comparing mental illness narratives of
      Haredi male patients and their rabbis.
AB  - By comparing versions of mental illness narratives - told by Haredi (Utraorthodox
      Jews) male patients of a mental health clinic in Israel and by their rabbis -
      this paper relates to two distinct, yet interrelated, theoretical questions: the
      place and agency of narrators, and the tension between experience and
      representation. A pair of narratives exemplifies a pattern in which the patients
      (Talmudic students) tell a narrative of a sudden breakdown related to a dramatic
      meeting with a non-human figure (often, a woman) or force. Their rabbis, by
      contrast, tell a narrative that emphasizes their students' mundane symptoms,
      "abnormal" and "immoral" behavior, and use a local adaptation of a Western
      psychological explanatory model. A dynamic of inclusion and exclusion emerges as
      students are seeking legitimization and avoidance of stigma, while their rabbis
      are silencing themes that challenge social and cultural orders. The different
      narratives are further interpreted in the context of the micropolitics of the
      interviews and of identity politics between the Haredim and secular Israelis.
      This social dynamics shows how differently placed social actors-narrators
      interpreters construct differently contested and diverse cultural narratives of a
      seemingly shared reality.

PMID- 11453259
TI  - Practices of the pregnant self: compliance with and resistance to prenatal norms.
AB  - A major challenge of medical anthropology is to assess how biomedicine, as a
      vaguely-defined set of diverse texts, technologies, and practitioners, shapes the
      experience of self and body. Through narrative analyses of in-depth, semi
      structured interviews with 158 pregnant women in southern California, this paper
      explores how the culture of biomedicine, encountered formally at prenatal care
      check-ups and informally through diverse media, influences pregnant women's
      perceptions of appropriate prenatal behavior. In the spirit of recent social
      scientific work that draws on and challenges Foucauldian insights to explore
      social relations in medicine, we posit a spectrum of compliance and resistance to
      biomedical norms upon which individual prenatal practices are assessed. We
      suggest that pregnancy is, above all, characterized by a split subjectivity in
      which women straddle the authoritative and the subjugated, the objective and the
      subjective, and the haptic as well as the optic, in telling and often strategic
      ways. In so doing, we identify the intersection between the disciplinary
      practices of biomedicine and the practices of pregnant women as a means of
      furnishing more fruitful insights into the oft-used term "power" and its roles in
      constituting social relations in medicine.

PMID- 11453260
TI  - Genetic optimism: framing genes and mental illness in the news.
AB  - Over the past two decades the pace and specificity of discoveries associating
      genetics with mental illness has accelerated, which is reflected in an increase
      in news coverage about the genetics of mental disorder. The news media is a major
      source of public understanding of genetics and a strong influence on public
      discourse. This paper examines the news coverage of genetics and mental illness
      (i.e., bipolar illness and schizophrenia) over a 25 year period, emphasizing the
      peak period of 1987-1994. Using a sample of 110 news stories from 5 major
      American newspapers and 3 news magazines, we identify the frame of "genetic
      optimism" which dominated the reporting of genetics and mental illness beginning
      in the mid- 1980s. The structure of the frame is comprised of 3 elements: a gene
      for the disorder exists; it will be found; and it will be good. New discoveries
      of genes were announced with great fanfare, but the most promising claims could
      not be replicated or were retracted in short order. Despite these
      disconfirmations, genetic optimism persisted in subsequent news stories. While
      the scientific accuracy of the gene stories is high, the genetic optimism frame
      distorts some of the findings, misrepresents and reifies the impact of genes on
      mental disorder, and leaves no space for critics or an examination of potential
      negative impacts. The stances of reporters, scientists and editors may all in
      different ways contribute to the perpetuation of genetic optimism. Genetic
      optimism presents an overly sanguine picture of the state of genetics; as we
      enter the genetic age it is important to balance the extraneous "hype and hope"
      contained in news stories of genetics and mental illness.

PMID- 11453261
TI  - An evidence-based guideline for the management of uterine fibroids.

PMID- 11453262
TI  - Misoprostol versus dinoprostone for cervical priming prior to induction of labour
      in term pregnancy: a randomised controlled trial.
AB  - A prospective randomised controlled trial was performed to compare the efficacy
      and safety of intravaginal misoprostol to that of intravaginal dinoprostone when
      used for cervical priming prior to the induction of labour; 126 women were
      recruited to the study and randomised to receive either intravaginal dinoprostone
      (n = 63) or misoprostol (n = 63) for cervical priming prior to induction of
      labour. The mean time from insertion of the priming agent to vaginal delivery was
      significantly shorter in the misoprostol group (925.8 versus 1577.6 minutes), the
      mean duration of the active length of labour was significantly shorter in the
      misoprostol group (353.7 versus 496.8 minutes) and more women in the misoprostol
      group delivered in less than 12 hours (92% versus 76.5%). Women in the
      misoprostol group were less likely to require a repeated dose of prostaglandin
      for cervical priming and less likely to require oxytocin for augmentation of
      labour. There was no difference in the number of women who were delivered
      vaginally or by Ceasarean section between the two groups. More women developed
      hyperstimulation during labour in the misoprostol group; however there was no
      difference between the groups in neonatal outcome in respect to low cord pH or
      Apgar score at delivery or admission to the neonatal special care nursery.

PMID- 11453263
TI  - Operative vaginal delivery: clinical appraisal of a new vacuum extraction device.
AB  - The efficacy of a new vacuum extraction device, the Kiwi OmniCup, and its effects
      on mothers and infants were tested in a study of 18 non-rotational and 32
      rotational vacuum assisted deliveries. Forty-nine (98%) of the extractions
      resulted in successful vaginal births. Autorotation of the fetal head when the
      occiput was transverse or posterior was achieved in 31 (97%) of the 32 vacuum
      procedures. The high success rates recorded for both vaginal delivery and
      autorotation of the fetal head were largely attributable to the fact that flexing
      cup applications were achieved in 90 % of the vacuum attempts. There were no
      cases of serious maternal trauma or clinically significant neonatal injuries. Two
      infants had cephalohaematomas and one infant developed a small subgaleal
      haemorrhage following a difficult delivery, which resolved rapidly without
      complications. It was concluded that the Kiwi OmniCup is an efficient and safe
      vacuum device for assisted vaginal delivery, provided it is used correctly and
      appropriately.

PMID- 11453264
TI  - Faecal incontinence after vaginal delivery: a review.

PMID- 11453265
TI  - Levels of knowledge of Down syndrome and Down syndrome testing in Australian
      women.
AB  - At their first hospital antenatal visit, 209 women were interviewed to explore
      their level of knowledge of Down syndrome and the available prenatal tests.
      Overall, the women had limited knowledge. Non-Caucasian women had less knowledge
      of Down syndrome, available prenatal tests and the association of Down syndrome
      with advanced maternal age than Caucasian women. Women with a history of a
      previous pregnancy and women over 35 years of age were not more aware of Down
      syndrome or the available tests than other women. These findings have significant
      implications for antenatal education and the implementation of screening programs
      for Down syndrome.

PMID- 11453266
TI  - The fetal inflammatory response syndrome and cerebral palsy: yet another
      challenge and dilemma for the obstetrician.
AB  - There is increasing evidence demonstrating a relationship between intrauterine
      infection and the development of neonatal intraventricular haemorrhage and
      periventricular leukomalacia with the subsequent occurrence of cerebral palsy,
      which is thought to be mediated through the generation of pro-inflammatory
      cytokines by the fetus. In the light of this relationship, a review of the
      current management of intrapartum infection and the associated complications of
      intrauterine infection such as preterm labour and preterm premature rupture of
      the membranes would seem timely along with the development of potential
      strategies which might prevent or ameliorate the effects of the fetal
      inflammatory response syndrome. The suggested changes in the understanding and
      management of the fetal inflammatory response syndrome provide a challenge and
      pose a dilemma for the practising obstetrician.

PMID- 11453267
TI  - Is there an interaction between cervical length and cervical microbiology in the
      pathogenesis of preterm labour?
AB  - Transvaginal ultrasound of the cervix is increasingly used to estimate cervical
      length during pregnancy. Initially used to determine a possible need for cervical
      suture, the technique has been shown to be of value in the prediction of preterm
      delivery In addition, bacterial vaginosis has been shown to be associated with an
      increased risk of preterm delivery. We hypothesised that shortening of the cervix
      and potential cervical pathogens, in particular the presence of bacterial
      vaginosis, act synergistically in the pathogenesis of premature labour. Three
      hundred and sixteen women were recruited for prospective longitudinal follow-up,
      with both transvaginal ultrasound and cervical bacteriology performed at
      approximately 18 and 28 weeks gestation. A strong correlation was found between a
      shortened cervix and preterm delivery (p<0.02 at 18 weeks; p<0.001 at 28 weeks).
      Women with both a short cervix and cervical pathogens had the highest risk of
      preterm delivery (43%), although not significantly greater than a short cervix
      with normal cervical flora (31% preterm delivery). In the presence of a normal
      cervical length, preterm delivery rates in the presence of normal flora and
      potential cervical pathogens were much lower (9% and 5% respectively).

PMID- 11453268
TI  - Effects of ethnicity on glucose tolerance, insulin resistance and beta cell
      function in 223 women with an abnormal glucose challenge test during pregnancy.
AB  - This study was conducted to investigate body-mass-index (BMI), insulin resistance
      and beta cell function in a group of pregnant women. Two hundred and twenty-three
      consecutive women with an abnormal 50 g glucose challenge test in the third
      trimester were studied. All underwent oral glucose tolerance testing; 97 had a
      100 g test and 126 a 75 g test. Fasting insulin was measured. Insulin resistance
      and beta cell function were calculated using the homeostasis model. Among the 136
      Caucasian, 60 Asian, 11 Indian and 16 Arabic women studied, there were no age
      differences. Arabic women had higher parity (p < 0.05). Asian women had lower BMI
      than Caucasian (p < 0.001), Indian (p < 0.01), and Arabic women (p < 0.01). Women
      with gestational diabetes had higher insulin resistance than women with normal
      glucose tolerance (2.9+/-4.0 vs. 2.3 +/- 2.5 p = 0.025). Women with gestational
      diabetes tended to have lower beta cell function 199 +/- 203 vs. 247 +/-380 p =
      0.08). Asian women had higher glucose levels than Caucasian women after 50 g
      challenge (8.9 +/- 2.1 mmol/1 vs. 8.6 +/- 1.6; p = 0.034). Asian women were more
      likely to have gestational diabetes than Caucasian women (31.7% vs. 14%; p =
      0.02). Fasting glucose and insulin were comparable in Asian and Caucasian women.
      Mean insulin resistance and beta cell function in Asian and Caucasian women were
      not significantly different. We concluded that Asian women had lower BMI than
      Caucasian women. Women with gestational diabetes were more insulin resistant.
      Insulin resistance and beta cell function in Asian and Caucasian women are
      similar. Gestational diabetes in Asian women is of similar aetiology to that seen
      in Caucasian women, but occurs at a lower BMI.

PMID- 11453269
TI  - Accuracy and modifying factors of the sonographic estimation of fetal weight in a
      high-risk population.
AB  - There have been a number of reviews assessing the accuracy of different methods
      of sonographic estimation of fetal weight, without identifying any clearly
      superior equation. In order to optimise accuracy in a high-risk population, we
      decided to compare some of the most popular early equations with the newer volume
      based equations, and to try and identify factors that affect the ability of these
      equations to estimate fetal weight accurately We collected the scan and delivery
      details of 192 fetuses born within one week of a sonographic estimation of fetal
      weight. We then applied three of the most popular equations and two newer volume
      based equations to the recorded fetal biometric parameters to assess the
      performance of each equation overall, and under varying maternal, fetal, and scan
      conditions. The equations of Shepard, Hadlock A, Hadlock B and Combs produced
      similar results with systematic (mean) errors in the range 1.2-1.9% and random
      error characterised by one standard deviation in the range of 8.6-9.5%. Dudley's
      volume-based equation produced a significant systematic error in the form of a
      mean error of 7.4%, which corresponds to a mean birthweight (BW) which is 7.4%
      above the mean estimated fetal weight (EFW). When we stratified the study group
      by birthweight, Combs' equation produced significant differences in the mean
      error, (p < 0.00001), that ranged from a mean overestimation in fetal weight of
      8.5% for babies with BW < 1000 g to a mean underestimation in fetal weight of
      6.2% for babies with BW > 3000 g. Oligohydramnios resulted in a trend towards an
      increased mean error for all equations which was only statistically significant
      for Hadlock B. The equations Shepard and Hadlock A performed best in our high
      risk population. They produced the smallest systematic errors across the entire
      study group and were not adversely affected by variations in birthweight, liquor
      volume, or fetal presentation. The newer, volume-based equations were
      disappointing, producing large systematic errors. Large random errors in all
      equations continue to be the Achilles' heel that limit the value of sonographic
      EFW.

PMID- 11453270
TI  - Transvaginal cervico-isthmic cerclage: a simple approach.
AB  - In this article, we describe a relatively simple surgical option that we believe
      is indicated for use in cases of cervical incompetence. We discuss the advantages
      of this procedure to the surgeon and patient, and give details of 59 patients who
      have undergone this procedure one or more times over a 13-year period. A short
      review of the history of treatment of cervical incompetence and of recent trends
      for its management is also presented.

PMID- 11453271
TI  - Laparoscopic presacral neurectomy - retrospective series.
AB  - A retrospective audit of medical records was conducted for one surgeon (AL). All
      patients who underwent laparoscopic presacral neurectomy for severe midline
      dysmenorrhoea were identified. Details of the preoperative symptoms, clinical
      findings and operative records were studied. Improvement of dysmenorrhoea was
      assessed according to a pain scale. Twelve patients who had a laparoscopic
      presacral neurectomy performed were identified. Eight patients reported
      significant improvement of symptoms, with a further two reporting mild
      improvement. Two patients failed to show any improvement of symptoms. We believe
      that the role of laparoscopic presacral neurectomy should be limited to patients
      with severe midline dysmenorrhoea not responding to the medical therapy. It may
      be a supplementary procedure to laparoscopic resection of endometriosis or
      adhesiolysis.

PMID- 11453272
TI  - An improved system of bladder drainage.
AB  - We report the successful use of a modified No. 8 infant feeding tube for
      postoperative bladder drainage in 100 gynaecological patients after surgery In
      previous years, problems arising from the use of trans-urethral postoperative
      catheter drainage led to the use of various types of suprapubic catheter drainage
      after gynaecological surgery However, this method of catheter drainage still
      carries the risk of complications, and many surgeons have preferred to persist
      with trans-urethral bladder drainage. Several authors have described the
      postoperative use of a small diameter transurethral feeding tube so as to enable
      the patient to void around the tube, thus avoiding the risks of repeated
      reinsertion of a catheter if there is delay in reestablishment of normal voiding.
      The simplicity of this method and its low cost encouraged us to carry out a trial
      of the method and we have introduced some modifications to improve the technique.
      Our experience of the method and the positive comments from nursing staff and
      patients have led us to adopt it for most of our postoperative gynaecological
      patients and we believe it deserves wider use.

PMID- 11453273
TI  - The impact of ethnicity on the presentation of polycystic ovarian syndrome.
AB  - The effect of ethnicity on the prevalence and presentation of polycystic ovarian
      syndrome (PCOS) was examined in a cross-sectional study of women with clinical -
      and ultrasound - diagnosed PCOS. European, Maori and Pacific Island women were
      seen in proportion to the general population, whereas Indian women were over
      represented and Chinese women under-represented. European and Maori women were
      more likely to present with hirsutism than other ethnic groups (43% versus 25%, p
      < 0.05), while European women were less likely to present with infertility (46%
      versus 68%, p < 0.01). The Pacific Island women had little or no acne but other
      signs of PCOS were similar among ethnic groups. Although less than 10% of
      patients were referred with obesity, the majority of PCOS women were overweight
      on examination. Maori and Pacific Island women were more obese and had the
      highest rates of insulin resistance and lipid abnormalities. The adverse
      metabolic profile of many of these women, particularly the Maori and Pacific
      Islanders, is very likely to predispose them to early cardiovascular disease.

PMID- 11453274
TI  - What is the probability of conception for couples entering an IVF program?
AB  - The outcome of 4225 couples undergoing 8207 in vitro fertilisation (IVF) cycles
      over a six year period has been analysed using life table analysis. Pregnancy was
      expressed as a 'clinical pregnancy - fetus visible on ultrasound' per stimulated
      cycle oocyte collection, with pregnancies obtained from frozen embryos being
      referred to the cycle where they were collected. We found that only 1 in 200
      patients proceeded beyond six cycles and the cumulative per cent pregnant was
      20.7% after the first cycle, with nearly half pregnant within three and over two
      thirds being pregnant within six cycles. We find this is a useful way to present
      the chance of pregnancy to prospective couples.

PMID- 11453275
TI  - Follicular flushing at oocyte retrieval: a reappraisal.
AB  - A survey of Australian assisted reproduction technique (ART) units revealed many
      (> 50%) use flushing of the follicle in addition to direct aspiration of the
      fluid during oocyte retrieval. The rationale is that flushing offers an advantage
      to the patient, with a larger number of oocytes being collected and thus a higher
      potential for pregnancy Following a complication in a patient, the medical staff
      determined that flushing might have been implicated. While this was later shown
      to be unfounded, the unit changed the method of oocyte collection, thus providing
      an opportunity historically to evaluate the differences between aspiration of
      follicular fluid alone or with additional flushing of each follicle. Thus the aim
      of this analysis was to test the hypothesis that aspiration alone does not effect
      the outcomes of ART with respect to oocyte numbers collected, their quality and
      subsequent fertilisation, or ultimate pregnancy rate in a large patient group (n
      = 2378). During the review period (1991-1993) the manufacturer of the aspiration
      needles; the pump and pressure used for aspiration; the staff involved in all
      procedures; and the premises, equipment and media used for oocyte collection and
      culture remained constant. Similarly the two patient groups did not differ in
      their demographics and physical characteristics. There was no difference (p >
      0.5) in the number of oocytes collected, the number of embryos created or the
      pregnancy rate for that treatment cycle. There was also no significant difference
      between the two groups in fertilisation rates, irrespective of the type of
      treatment being used in vitro fertilisation (IVF), gamete intrafallopian transfer
      (GIFT) or intracytoplasmic sperm injection (ICSI)). The data presented in this
      paper are not prospective. They use historical comparison and are confounded by
      minor changes in ovarian stimulation protocols, but the conclusions are still
      valid. These data suggest there is no difference in the outcome of ART (from
      oocyte collection through to pregnancy rate) whether or not aspiration of
      follicles is accompanied by flushing. First principles of surgery advocate the
      shortest possible operating time, the simplest procedure and minimum amount of
      tissue handling as maxims for reducing complication. Therefore, as a routine,
      flushing would seem superfluous in ART.

PMID- 11453276
TI  - Repeat doses of prenatal corticosteroids do not increase the risk of acute
      chorioamnionitis.

PMID- 11453277
TI  - Body composition and energy metabolism in pregnancy.
AB  - The objective of the study was to measure energy metabolism and body composition
      during pregnancy and postpartum, compared to non-pregnant women, using non
      invasive techniques. A longitudinal study of eight normotensive pregnant women
      was carried out at 19 +/- 1 and 36+/-1 weeks gestation, and postpartum. A cross
      sectional study was also performed comparing postpartum to 12 non-pregnant women.
      Indirect calorimetry was performed while fasting to measure basal metabolic rate
      (BMR) and postprandially to measure diet-induced thermogenesis (DIT). Body
      composition consists of fat mass, lean body mass (LBM), and total body water
      (TBW) and was measured by bio-electrical impedance. Insulin resistance was
      indirectly assessed by glucose and insulin concentration and DIT.

PMID- 11453278
TI  - Fetal thyrotoxicosis after maternal thyroidectomy.
AB  - Thyroid disease commonly presents in women in their reproductive years. Maternal,
      fetal and neonatal outcomes are very good if the diagnosis is made early and
      appropriate management pathways are established. In the uncommon situation of
      concurrent maternal and fetal disease, the key management issues involve
      recognition of the involvement of the fetus and close intensive surveillance of
      both mother and fetus/neonate using a multi-disciplinary approach. This approach,
      utilising a combination of serial ultrasound of the fetus and serial biochemical
      testing for the mother, allows for the accurate titration of medical therapy to
      both patients.

PMID- 11453279
TI  - Tubo-ovarian abscess in a non-sexually active female.

PMID- 11453280
TI  - Osteoma of the ovary causing obstructed labour.

PMID- 11453281
TI  - Extreme uterine herniation in pregnancy through an umbilical defect.

PMID- 11453282
TI  - Trial of labour after four Caesarean sections: a case report and literature
      review.
AB  - We present the case of a woman who requested trial of labour following four
      Caesarean sections and achieved a vaginal birth. We discuss the recent legal
      rulings pertaining to patient consent in respect to Caesarean section and
      published data on outcomes following trial of labour after more than 1 Caesarean
      section.

PMID- 11453283
TI  - Amoebic liver abscess in pregnancy.
AB  - We describe the case of an amoebic liver abscess (ALA) presenting in the third
      trimester of pregnancy which raised both diagnostic and treatment dilemmas as
      well as being associated with preterm labour. Amoebic liver abscess is caused by
      the protozoan organism Entamoeba histolytica which is endemic in many parts of
      the developing world. Invasion of the colonic mucosa results in the clinical
      syndrome of amoebic dysentery and in some cases dissemination to the liver or
      other organs occurs resulting in abscess formation. Amoebic liver abscess is a
      rare complication of pregnancy and there are few reports in the world literature,
      these being mostly from endemic areas. We present here the case of a caucasian
      female who presented with an amoebic liver abscess in the third trimester of
      pregnancy, thirteen months after returning to Australia from a short holiday in
      Bali.

PMID- 11453284
TI  - Unresponsive puerperal fever: early recourse to imaging studies aids diagnosis.

PMID- 11453285
TI  - Cardioversion in the third trimester of pregnancy.

PMID- 11453286
TI  - Developmental stage sensitivity and mode of action information for androgen
      agonists and antagonists.
AB  - The response from exposure to a toxic agent during development may vary depending
      on the dose, time of exposure and the mode of action. The mode of action and
      developmental stage sensitivity are established only for a limited number of
      chemical classes. Some aspects of developmental stage sensitivity that appear to
      affect the response to androgen agonists and antagonists are the levels and
      distribution of endogenous androgens and the androgen receptor at particular
      times during development. This information is summarized and discussed as it
      relates to two critical windows of development: the period of male reproductive
      tract differentiation, and the peripubertal period when male sexual maturation
      occurs. Developmental stage sensitivity and mode of action data for the androgen
      antagonist vinclozolin are reviewed. Vinclozolin acts by binding to and
      activating the androgen receptor and affects a number of endpoints of
      reproductive tract differentiation as well as pubertal maturation. Approaches to
      incorporating mode of action, developmental stage sensitivity, and dose/potency
      information into risk assessment, as well as the additional data needed for using
      mode of action information, both qualitatively and quantitatively, in risk
      assessment are discussed. These issues are also considered in the context of
      combining the risks of exposure to two or more chemicals with similar modes of
      action.

PMID- 11453287
TI  - Biological effects of embedded depleted uranium (DU): summary of armed forces
      radiobiology research institute research.
AB  - The Persian Gulf War resulted in injuries of US Coalition personnel by fragments
      of depleted uranium (DU). Fragments not immediately threatening the health of the
      individuals were allowed to remain in place, based on long-standing treatment
      protocols designed for other kinds of metal shrapnel injuries. However, questions
      were soon raised as to whether this approach is appropriate for a metal with the
      unique radiological and toxicological properties of DU. The Armed Forces
      Radiobiology Research Institute (AFRRI) is investigating health effects of
      embedded fragments of DU to determine whether current surgical fragment removal
      policies remain appropriate for this metal. These studies employ rodents
      implanted with DU pellets as well as cultured human cells exposed to DU
      compounds. Results indicate uranium from implanted DU fragments distributed to
      tissues far-removed from implantation sites, including bone, kidney, muscle, and
      liver. Despite levels of uranium in the kidney that were nephrotoxic after acute
      exposure, no histological or functional kidney toxicity was observed. However,
      results suggest the need for further studies of long-term health impact, since DU
      was found to be mutagenic, and it transformed human osteoblast cells to a
      tumorigenic phenotype. It also altered neurophysiological parameters in rat
      hippocampus, crossed the placental barrier, and entered fetal tissue. This report
      summarizes AFRRI's depleted uranium research to date.

PMID- 11453288
TI  - Behavioral sensitization following exposure to low doses of trimethylolpropane
      phosphate.
AB  - Behavioral sensitization is commonly studied within the context of drugs known to
      directly increase activity in the brain's dopamine system, particularly drugs of
      abuse. However, the present research suggests such behavioral changes can also be
      observed following exposure to other compounds that indirectly affect the
      dopamine system. One such compound is trimethylolpropane phosphate (TMPP), a
      bridged organophosphate that can be produced by the partial pyrolysis of certain
      synthetic lubricants used on military ships and aircraft. Although TMPP is a
      potent convulsant, it has been demonstrated that treatment with doses below
      seizure threshold results in long-term behavioral sensitization. The effect has
      been demonstrated with a number of neurobehavioral endpoints, particularly those
      assessing appetitive responding. More specifically, sensitization has been
      observed in acquisition of schedule-induced polydipsia (SIP), appetitive
      reinforcer approach sensitization (ARAS) and social interaction as measured in
      neonatal ultrasonic vocalizations, juvenile play and adult conspecific approach.
      Overall, the rats demonstrated a heightened appetitive response pattern. More
      specifically, TMPP reliably reduced the number of SIP sessions necessary to
      induce asymptotic drinking level and increased the time spent investigating
      (sniffing) a food reinforcer as measured in the ARAS task. Specific effects of
      TMPP on social interaction were an increase in ultrasonic vocalizations when the
      neonate was isolated from the dam and littermates and an increase in both
      measures of juvenile play (pins and dorsal contacts). A complex set of
      interactions emerged for the measures of adult social investigation where the
      drug effect was modulated by such factors as sex and neutral vs. stress-inducing
      experiences coincident with the drug treatment. In contrast to the above results,
      no behavioral changes were recorded for measures in the elevated plus maze and
      open field exploration. These results suggest that TMPP produces
      neurophysiological changes that persist much longer than the pharmacological
      effect of the compound, particularly in the neural correlates for appetitive
      behavior.

PMID- 11453289
TI  - Quantitative structure-pharmacokinetic relationship modelling.
AB  - This article presents the current methods in quantitative structure
      pharmacokinetic relationship (QSPkR) modelling along with examples using
      chemicals of toxicological significance. The common method involves: (i)
      collecting pharmacokinetic data or determining pharmacokinetic parameters (e.g.
      elimination half-life, volume of distribution) by fitting to experimental data;
      and (ii) associating them with the structural features of chemicals using a Free
      Wilson model. Such QSPkRs have been developed for a few series of chemicals but
      their usefulness is limited to the exposure scenario and conditions under which
      the experimental data were originally collected. The alternative approach
      involves the development of quantitative structure-property relationship (QSPR)
      models for parameters, blood:air partition coefficient, tissue:blood partition
      coefficient, maximal velocity for metabolism and Michaelis affinity constant, of
      physiologically-based pharmacokinetic (PBPK) models which are useful for
      conducting species, route, dose and scenario extrapolations of the tissue dose of
      chemicals. Mechanistic QSPRs are available for predicting tissue:blood and
      blood:air partition coefficients from molecular structure information of
      chemicals, whereas such approaches are not currently available for hepatic
      metabolism parameters. However, at the present time, the pharmacokinetics of
      inhaled volatile organic chemicals can be simulated adequately by considering the
      physiological limits of the hepatic extraction ratio (0-1) and molecular
      structure-based estimates of partition coefficients in the PBPK model. This
      current state-of-the-art of structure-based modelling of pharmacokinetics will
      advance with the development of QSPRs for other chemical-specific parameters of
      PBPK models. Integrated QSPR-PBPK modelling should facilitate the identification
      of chemicals of a family that possess desired properties of bioaccumulation and
      blood concentration profile in both test animals and humans.

PMID- 11453290
TI  - Towards environmental toxicogenomics -- development of a flow-through, high
      density DNA hybridization array and its application to ecotoxicity assessment.
AB  - Assessment of the environmental hazard posed by soils/sediments containing low to
      moderate levels of contaminants using standard analytical chemical methods is
      uncertain due (in part) to a lack of information on contaminant bioavailability,
      the unknown interactive effects of contaminant mixtures, our inability to
      determine the species of a metal in an environmental matrix, and the relative
      sensitivity of bioassay species. Regulatory agencies compensate for this
      uncertainty by lowering cleanup goals, but in this process they effectively
      exclude otherwise attractive cleanup options (i.e. bioremediation). Direct
      evaluations of soil and sediment toxicity preclude uncertainty from most of these
      sources. However, the time and cost of chronic toxicity tests limits their
      general application to higher levels of tiered toxicity assessments.
      Transcriptional level (mRNA) toxicity assessments offer great advantages in terms
      of speed, cost and sample throughput. These advantages are currently offset by
      questions about the environmental relevance of molecular level responses. To this
      end a flow-through, high-density DNA hybridization array (genosensor) system
      specifically designed for environmental risk assessment was developed. The
      genosensor is based on highly regular microchannel glass wafers to which gene
      probes are covalently bound at discrete (200-microm diameter spot) and
      addressable (250-microm spot pitch) locations. The flow-through design enables
      hybridization and washing times to be reduced from approximately 18 h to 20 min.
      The genosensor was configured so that DNA from 28 environmental samples can be
      simultaneously hybridized with up to 64 different gene probes. The standard
      microscopic slide format facilitates data capture with most automated array
      readers and, thus high sample throughput (> 350 sample/h). In conclusion,
      hardware development for molecular analysis is enabling very tractable means for
      analyzing RNA and DNA. These developments have underscored the need for further
      developmental work in probe design software, and the need to relate
      transcriptional level data to whole-organism toxicity indicators.

PMID- 11453291
TI  - The development of a stochastic physiologically-based pharmacokinetic model for
      lead.
AB  - This presentation describes the development of a prototype Monte Carlo module for
      the physiologically-based pharmacokinetic (PBPK) model for lead, created by Dr
      Ellen O'Flaherty. The module uses distributions for the following: exposure
      parameters (soil and dust concentrations, daily soil and ingestion rate, water
      lead concentration, water ingestion rate, air lead concentration, inhalation rate
      and dietary lead intake); absoption parameters; and key pharmacokinetic
      parameters (red blood binding capacity and half saturation concentration).
      Distributions can be specified as time-invariant or can change with age. Monte
      Carlo model predicted blood levels were calibrated to empirically measured blood
      lead levels for children living in Midvale, Utah (a milling/smelting community).
      The calibrated model was then evaluated using blood lead data from Palmerton,
      Pennsylvania (a town with a former smelter) and Sandy, Utah, (a town with a
      former smelter and slag piles). Our initial evaluation using distributions for
      exposure parameters showed that the model accurately predicted geometric (GM)
      blood lead levels of Palmerton and Sandy and slightly over predicted the GSD.
      Consideration of uncertainty in red blood cell parameters substantially inflated
      the GM. Future model development needs to address the correlation among
      parameters and the use of parameters for long-term exposure derived from short
      term studies.

PMID- 11453292
TI  - In vitro toxicity assessment of a new series of high energy compounds.
AB  - Hydrazine is an aircraft fuel and propellant used by the US Air Force. Due to its
      toxicity the Propulsion Directorate of the Air Force Research Laboratory
      (AFRL/PR) has investigated alternative chemicals to replace hydrazine. AFRL/PR
      has synthesized a series of high energy chemicals (HECs), primarily hydrazine
      derivatives and amino containing compounds such as hydrazinium nitrate (HZN), 2
      hydroxyethyl-hydrazine nitrate (HEHN), diethyl hydrazine nitrate (DEHN),
      ethanolamine nitrate (EAN), histamine dinitrate (HDN) and methoxylamine nitrate
      (MAN) to study as alternative chemical candidates. Although HECs are reliable
      constituents of powered propellant systems, they constitute an important class of
      toxic agents to which military and civilian personnel can be exposed. The current
      study was undertaken to examine the toxicity of HECs in primary hepatocytes in
      vitro. The effects of short-term exposure (4 h) of hepatocytes to HECs were
      investigated with reference to viability, mitochondrial function and oxidative
      stress markers. The results showed a decrease in mitochondrial activity, increase
      in lactate dehydrogenase (LDH) leakage and depletion of reduced glutathione (GSH)
      levels. The levels of reactive oxygen species (ROS) increased dose dependently in
      HZN, MAN and HDN exposed cells. However, there was no induction of ROS generation
      in EAN, DEHN and HEHN exposed cells. Depletion of GSH in hepatocytes by
      buthionine sulfoximine (BSO) prior to exposure to HZN increased its toxicity. The
      results suggest that at least one mechanism of HEC toxicity is mediated through
      oxidative stress.

PMID- 11453293
TI  - Pet dogs as sentinels for environmental contamination.
AB  - The presence of environmental contaminants in air, water and food may pose
      significant health risks to the exposed human population. However, problems
      associated with assessing chronic exposure to low doses of environmental
      chemicals, multiple exposure routes, diseases with long latency periods, and non
      specific health outcomes make it difficult to conduct the appropriate human
      epidemiologic studies. It may be useful to complement human epidemiology with
      animal studies. Animals monitored or evaluated in situ for the appropriate suite
      of endpoints can provide information about both exposure levels and potential
      adverse health effects. Animals have served as sentinel indicators for health
      effects associated with a number of environmental exposures, including pesticides
      and asbestos. Pet dogs may be particularly valuable sentinels because they share
      the human environment. In addition, dogs respond to many toxic insults in ways
      analogous to humans, they have physiologically compressed life spans, and they
      are free from some important lifestyle risk factors for disease. An example of
      how pet dogs may be used as sentinels for potential human health hazards involves
      a study of the genotoxic effects resulting from exposure to a mixture of
      chemicals from nearby Superfund sites. We conducted a cross-sectional study of
      exposed dogs (living in the community with the Superfund sites) and controls
      (living in a nearby community). The pet owners completed a questionnaire, and we
      collected a blood sample from each dog. The blood samples were analyzed for
      standard clinical parameters and assays for possible genotoxic effects
      (peripheral blood lymphocyte micronucleus frequency and lymphocyte subtyping).
      Pet dogs living near the Superfund sites had a higher micronucleus frequency than
      control animals, suggesting that the dogs may have been exposed to environmental
      contaminants from these sites.

PMID- 11453294
TI  - Opportunities for using Navy marine mammals to explore associations between
      organochlorine contaminants and unfavorable effects on reproduction.
AB  - The Department of Defense (DoD) has a unique marine mammal program maintained by
      the US Navy that includes the largest force of bottlenose dolphins, Tursiops
      truncatus, worldwide. In recent years, this population of cetaceans that lives in
      netted open water enclosures in San Diego Bay has been monitored for levels of
      organochlorine (OC) contaminants in blubber, blood and milk. Data generated from
      these studies have afforded insight into the fate and possible effects of OC
      contaminants in marine mammals. We now report preliminary findings on the effects
      of maternal OC exposure on pregnancy outcome. Blubber OC levels were compared
      between females whose calves survived beyond 6 months and females whose calves
      were stillborn or died within 12 days of birth. The mean concentration of
      SigmaDDT was more than 3 times as high among dolphins whose calves died as that
      among dolphins whose calves survived beyond 6 months (P = 0.002). Mean SigmaPCB
      was more than 2.5 times higher in females whose calves did not survive (P=
      0.076). This population is a logical sentinel for the assessment of
      environmentally mediated disease. Biological tissues and fluids can be sampled on
      a regular basis from the dolphins for accumulation of tissue residues,
      facilitated by conditioned husbandry behaviors. These trained behaviors help
      preclude possible alterations in health measures resulting from capture stress.
      Animals' diets can be monitored for contaminant levels. With these data, the
      expertise and facilities available at the Navy laboratory and in collaboration
      with other experts in the field, controlled studies can be designed to monitor
      and assess dietary exposure, measurable immune and neurologic responses and
      assess reproductive and transgenerational effects of contaminants. Biomarkers can
      be developed to relate the health of individual animals relative to contaminant
      exposures. Such investigations of natural exposure and response scenarios are a
      logical adjunct to traditional laboratory toxicity studies.

PMID- 11453296
TI  - Infection transmission system models for microbial risk assessment.
AB  - Chemical risk assessments often focus on measuring exposure as if individuals
      were subject only to exogenous environmental sources of risk. For infectious
      diseases, exposure might not only depend on exogenous sources of microbes, but
      also on the infection status of other individuals in the population. For example,
      waterborne infections from agents such as Cryptosporidium parvum and Escherichia
      coli: O157:H7 might be transmitted from contaminated water to humans through
      drinking water; from interpersonal contact; or from infected individuals to the
      environment, and back to other susceptible individuals. These multiple pathways
      and the dependency of exposure on the prevalence of infection in a population
      suggest that epidemiological models are required to complement standard risk
      assessments in order to quantify the risk of infection. This paper presents new
      models of infection transmission systems that are being developed for the US
      Environmental Protection Agency as part of a project to quantify the risk of
      microbial infection. The models are designed to help inform water treatment
      system design decisions.

PMID- 11453295
TI  - Oxidative stress in zebrafish cells: potential utility of transgenic zebrafish as
      a deployable sentinel for site hazard ranking.
AB  - In order to quickly assess potential environmental hazards of forwardly deployed
      military bases, we have focussed our efforts on biochemical and molecular changes
      in vertebrate cells following exposure to aqueous soil extracts. To this end, we
      are designing a series of deployable transgenic fish. Fish exhibit many of the
      same general defenses against toxic chemicals as do mammals, including enzyme
      induction, and the generation of oxidative stress. In response to many foreign
      compounds that generate oxidative stress, the transcription of certain protective
      genes is induced via specific DNA motifs called electrophile response elements
      (EPREs). We have made a plasmid construct containing a single murine EPRE fused
      to a minimal promoter and the cDNA encoding firefly luciferase (EPRE-LUC). In
      this paper, we have shown that the treatment of zebrafish cell line ZEM2S with a
      variety of chemicals known to induce EPRE-dependent transcription in cultured
      mammalian cells, results in dose-dependent induction of the transiently
      transfected EPRE-LUC reporter construct. Compounds tested include aromatic
      hydrocarbons, heavy metals, and organophosphates. We observed similar dose
      dependent responses when we treated ZEM2S and human cells in vitro with identical
      aqueous extracts of soil from hazardous waste sites. This suggests that the
      mechanism by which these compounds activate transcription is well conserved
      between mammals and zebrafish, and that transgenic zebrafish lines containing
      EPRE-driven reporter constructs might be useful as sentinels for the early
      detection of oxidative stress-inducing chemicals.

PMID- 11453297
TI  - In vitro toxicities of experimental jet fuel system ice-inhibiting agents.
AB  - One research emphasis within the Department of Defense has been to seek the
      replacement of operational compounds with alternatives that pose less potential
      risk to human and ecological systems. Alternatives to glycol ethers, such as
      diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel
      system ice-inhibiting agents (FSIIs). This group of chemicals includes three
      derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M
      27). In addition, M-DE was evaluated as a reference compound. Our approach was to
      implement an in vitro test battery based on primary rat hepatocyte cultures to
      perform initial toxicity evaluations. Hepatocytes were exposed to experimental
      chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples
      were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity,
      glutathione level, and rate of protein synthesis as indicators of toxicity. Of
      the compounds tested, M-1, especially at the 10-mM dose, appeared to be more
      potent than the other chemicals, as measured by these toxicity assays. M-DE, the
      current FSII, elicited little response in the toxicity assays. Although some
      variations in toxicity were observed at the 10-mM dose, the in vitro toxicities
      of the chemicals tested (except for M-1) were not considerably greater than that
      of M-DE.

PMID- 11453298
TI  - Use of a toxicokinetic model in the analysis of cancer mortality in relation to
      the estimated absorbed dose of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin,
      TCDD).
AB  - We performed an analysis of All cancer and Lung cancer mortality in relation to
      estimated absorbed dose of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) in
      the cohort of chemical workers at 12 US plants assembled by the US National
      Institute for Occupational Safety and Health (NIOSH) (n = 5172). Estimates of
      cumulative exposure to TCDD were based on a minimal physiologic toxicokinetic
      model (MPTK) that accounts for inter- and intra-individual variations in body
      mass index (BMI) over time. Population-level parameters related to liver
      elimination and background (input or concentration) of TCDD were estimated from
      separate data with repeated measures of serum TCDD (US Air Force Health Study).
      An occupational TCDD input parameter was estimated based on one-point-in-time
      TCDD data available for a subset (n = 253) of the NIOSH cohort. Model-based time
      dependent cumulative dose estimates (area under the curve (AUC) of the lipid
      adjusted serum TCDD concentration over time) were obtained for members of the
      full cohort with recorded body height and weight (n = 4049), as this information
      is required by the MPTK model to compute dose. Missing-value problems arose in
      the estimation of the occupational input parameter (n = 42) and in TCDD-dose
      calculation in the full cohort (n = 886) and they were handled with multiple
      imputation methods. Risk-regression analyses were based on Cox log-linear models
      including age at entry, year of entry and duration of employment as categorical
      covariates in addition to the logarithm of cumulative TCDD dose in ppt-years.
      Risk sets were stratified on birth cohort. Estimates of the unlagged exposure
      coefficient in these models were 0.1249 [95% confidence interval (CI) 0.0144,
      0.2354] for All cancer and 0.2158 (95% CI 0.02376, 0.4078) for lung cancer. A 10
      year lag produced an increase in the estimate for all cancer (0.1539, 95% CI
      0.0387, 0.2691), whereas, the estimate for lung cancer was not affected much
      (0.2125, 95% CI 0.0138, 0.4112). At a dose level of 100 times the background the
      estimates obtained with a 10-year lag translate into a relative risk of 2.03 (95%
      CI 1.19-3.45) for all cancer and of 2.66 (95% CI 1.07-6.64) for lung cancer.
      Higher estimates of the exposure coefficients were obtained after imputation of
      missing values. This increase in risk seemed due to the inclusion of short-term
      workers, who may exhibit a higher mortality for reasons other than dioxin
      exposure.

PMID- 11453299
TI  - Ecological risk assessment of multimedia hazardous air pollutants: estimating
      exposure and effects.
AB  - Hazardous air pollutants, some of which have the potential for multimedia
      distribution, raise several hurdles for ecological risk assessment including: (1)
      the development of an adequate transport, fate and exposure model; and (2) the
      selection of exposure-response models that can accommodate multiple exposure
      routes for ecological receptors. To address the first issue, the EPA Office of
      Air Quality Planning and Standards has developed TRIM.FaTE, a mass-balance, fate,
      transport, and ecological exposure model that is a component of the Total Risk
      Integrated Methodology (TRIM) for air pollutants. In addition to abiotic
      transfers and transformations, TRIM.FaTE estimates the uptake of a chemical by
      terrestrial and aquatic organisms with time. Measures of exposure that TRIM.FaTE
      can provide include: (1) body burdens or tissue concentrations; (2) doses
      averaged over any time period; or (3) concentrations of chemicals in abiotic
      media. The model provides the user with the flexibility to choose the exposure
      response thresholds or dose-response relationships that are best suited to data
      availability, routes of exposure, and the mechanism of toxicity of the chemical
      to an ecological receptor. One of the challenges of incorporating TRIM.FaTE into
      a risk assessment methodology lies in defining a streamlined model simulation
      scenario for initial screening-level risk assessments. These assessments may
      encompass multiple facilities that emit a variety of pollutants near diverse
      ecosystems. The information on ecological risk assessment methodology that is
      described is applicable to the EPA Residual Risk Program with emphasis on
      multimedia pollutants and the role of TRIM.FaTE.

PMID- 11453300
TI  - Ecological conceptual models: a framework and case study on ecosystem management
      for South Florida sustainability.
AB  - The Everglades and South Florida ecosystems are the focus of national and
      international attention because of their current degraded and threatened state.
      Ecological risk assessment, sustainability, and ecosystem and adaptive management
      principles and processes are being used nationally as a decision and policy
      framework for a variety of types of ecological assessments. The intent of this
      study is to demonstrate the application of these paradigms and principles at a
      regional scale. The effects-directed assessment approach used in this study
      consists of a retrospective, eco-epidemiological phase to determine the causes
      for the current conditions and a prospective predictive risk-based assessment
      using scenario analysis to evaluate future options. Embedded in these assessment
      phases is a process that begins with the identification of goals and societal
      preferences which are used to develop an integrated suite of risk-based and
      policy relevant conceptual models. Conceptual models are used to illustrate the
      linkages among management (societal) actions, environmental stressors, and
      societal/ecological effects, and provide the basis for developing and testing
      causal hypotheses. These models, developed for a variety of landscape units and
      their drivers, stressors, and endpoints, are used to formulate hypotheses to
      explain the current conditions. They are also used as the basis for structuring
      management scenarios and analyses to project the temporal and spatial magnitude
      of risk reduction and system recovery. Within the context of recovery, the
      conceptual models are used in the initial development of performance criteria for
      those stressors that are determined to be most important in shaping the
      landscape, and to guide the use of numerical models used to develop quantitative
      performance criteria in the scenario analysis. The results will be discussed
      within an ecosystem and adaptive management framework that provides the
      foundation for decision making.

PMID- 11453301
TI  - Uncertainty and variability in risk from trophic transfer of contaminants in
      dredged sediments.
AB  - The risks associated with bioaccumulative contaminants must be considered when
      evaluating dredged material disposal alternatives. The bioaccumulation of
      organochlorines and other contaminants by higher trophic level organisms
      represents one of the most significant sources of uncertainty in risk assessment.
      Both population variability (e.g. true population heterogeneity in body weight,
      lipid content, etc.) and uncertainty (e.g. measurement error) in trophic transfer
      can lead to large errors in predicted risk values for ecological receptors. This
      paper describes and quantitatively evaluates sources of uncertainty and
      variability in estimating the risk to an ecological receptor (osprey) from the
      trophic transfer of polychlorinated biphenyls (PCBs) in sediments from the New
      York-New Jersey (NY-NJ) Harbor. The distribution of toxicity quotients is
      obtained using a food chain model for the osprey and specifying distributions for
      input parameters, which are disaggregated to represent either uncertainty or
      variability. PCB concentrations in sediment and water are treated as
      predominantly uncertain, whereas lipid content in fish, feeding preferences, and
      fish weight are assumed to contribute primarily to population variability in PCB
      accumulation. The analysis shows that point estimates of reasonable maximum
      exposure (RME) exceed the uncertainty bounds on the 95th percentile of
      variability. The analysis also shows that uncertainties in the sediment and water
      contaminant concentrations contribute more to the range of risk estimates than
      does the variability in the population exposure parameters. The separation of
      uncertainty and variability in food chain models can help to support management
      decisions regarding dredged material disposal by providing a quantitative
      expression of the confidence in ecological risk estimates. A rationale is
      provided for the distinction between uncertain and variable parameters based on
      management goals and data availability.

PMID- 11453302
TI  - An object-oriented framework for dynamic ecosystem modeling: application for
      integrated risk assessment.
AB  - Ecological risk assessment requires the integration of a wide range of data on
      anthropogenic processes, ecological processes and on processes related to
      environmental fate and transport. It is a major challenge to assemble a
      simulation system that can successfully capture the dynamics of complex
      ecological systems and an even more serious challenge to be able to adapt such a
      simulation to shifting and expanding analytical requirements and contexts. The
      dynamic information architecture system (DIAS) is a flexible, extensible, object
      based framework for developing and maintaining complex simulations. DIAS supports
      simulations in which the real-world entities that make up ecological systems are
      represented as software 'entity objects'. The object-oriented integrated dynamic
      landscape analysis and modeling system (OO-IDLAMS) provides a good example of how
      DIAS has been used to build a suite of models for the purpose of assessing the
      ecological impacts of military land use and land management practices. OO-IDLAMS
      is a prototype conservation modeling suite that provides military environmental
      managers and decision-makers with a strategic, integrated and adaptive approach
      to natural resources planning and ecosystem management. The OO-IDLAMS prototype
      used Fort Riley, Kansas as a case study to demonstrate DIAS' capabilities to
      offer flexibility, interprocess dynamics and cost-effective reuse of code for
      ecosystem modeling and simulation. DIAS can also readily lend itself to other
      applications in ecological risk assessment. It has great potential for the
      integration of ecological models (associated with biological uptake and effects)
      with environmental fate and transport models. A DIAS ecological risk assessment
      application could be used to predict the magnitude and extent of ecological risks
      and evaluate remedy effectiveness in a timely and cost-effective manner.

PMID- 11453303
TI  - Linking population-level risk assessment with landscape and habitat models.
AB  - Ecological risk assessment at the population level often involves predicting the
      effects of a particular change in the land-use patterns on the viability of
      native species. A common method of addressing such questions is modeling the
      metapopulation dynamics of the species in the landscape. However, the landscape
      and, as a result, the spatial structure of the metapopulation usually do not
      remain unchanged, thus the assessment of viability must incorporate the dynamic
      nature of the landscape. A new link being developed between a metapopulation
      modeling program (RAMAS) and a landscape dynamics program (LANDIS) will allow the
      transitional dynamics of the landscape to be incorporated into assessment of
      viability and threat. This approach combines methods of landscape prediction with
      those of metapopulation simulation. The link between the landscape model and
      metapopulation model is provided by statistical models of habitat suitability for
      the species in focus.

PMID- 11453304
TI  - Mode of action and tissue dosimetry in current and future risk assessments.
AB  - Two fundamental concepts have emerged to organize contemporary approaches to
      chemical risk assessment - mode of action and tissue dosimetry. Mode of action
      specifies the nature of the interactions between the chemical and the body that
      lead to toxic responses and should, under optimal circumstances, also specify the
      form of the tissue dose that leads to these effects. This paper highlights recent
      development of biologically based dose response (BBDR) models for specific toxic
      endpoints that use knowledge on mode of action to specify measures of dose. These
      dose measures then are used to support low dose and interspecies extrapolations.
      We first focus on a series of dose response models developed for several
      compounds that produce nasal toxicity. These examples demonstrate a range of
      model structures from simple dosimetry models (methylmethacrylate) to linkage of
      dosimetry with specific biological processes involved in carcinogenesis
      (formaldehyde). Two BBDR models with dioxin illustrate the organization of
      biological and dosimetry information into specific testable hypotheses that could
      distinguish these different models and lead to a more uniform approach to risk
      assessment for this compound. A final section discusses the impact of molecular
      biology and the genomic revolution in relation to development of BBDR models for
      specific toxic endpoints.

PMID- 11453305
TI  - Comparison of cancer risk estimates for vinyl chloride using animal and human
      data with a PBPK model.
AB  - Vinyl chloride (VC) is a trans-species carcinogen, producing tumors in a variety
      of tissues, from both inhalation and oral exposures, across a number of species.
      In particular, exposure to VC has been associated with a rare tumor, liver
      angiosarcoma, in a large number of studies in mice, rats, and humans. The mode of
      action for the carcinogenicity of VC appears to be a relatively straightforward
      example of DNA adduct formation by a reactive metabolite, leading to mutation,
      mistranscription, and neoplasia. The objective of the present analysis was to
      investigate the comparative potency of a classic genotoxic carcinogen across
      species, by performing a quantitative comparison of the carcinogenic potency of
      VC using data from inhalation and oral rodent bioassays as well as from human
      epidemiological studies. A physiologically-based pharmacokinetic (PBPK) model for
      VC was developed to support the target tissue dosimetry for the cancer risk
      assessment. Unlike previous models, the initial metabolism of VC was described as
      occurring via two saturable pathways, one representing low capacity-high affinity
      oxidation by CYP2E1 and the other (in the rodent) representing higher capacity
      lower affinity oxidation by other isozymes of P450, producing in both cases
      chloroethylene oxide (CEO) and chloroacetaldehyde (CAA) as intermediate reactive
      products. Depletion of glutathione by reaction with CEO and CAA was also
      described. Animal-based risk estimates for human inhalation exposure to VC using
      total metabolism estimates from the PBPK model were consistent with risk
      estimates based on human epidemiological data, and were lower than those
      currently used in environmental decision-making by a factor of 80.

PMID- 11453306
TI  - Methodological issues of using observational human data in lung dosimetry models
      for particulates.
AB  - INTRODUCTION: The use of human data to calibrate and validate a physiologically
      based pharmacokinetic (PBPK) model has the clear advantage of pertaining to the
      species of interest, namely humans. A challenge in using these data is their
      often sparse, heterogeneous nature, which may require special methods. Approaches
      for evaluating sources of variability and uncertainty in a human lung dosimetry
      model are described in this study. METHODS: A multivariate optimization procedure
      was used to fit a dosimetry model to data of 131 U.S. coal miners. These data
      include workplace exposures and end-of-life particle burdens in the lungs and
      hilar lymph nodes. Uncertainty in model structure was investigated by fitting
      various model forms for particle clearance and sequestration of particles in the
      lung interstitium. A sensitivity analysis was performed to determine which model
      parameters had the most influence on model output. Distributions of clearance
      parameters were estimated by fitting the model to each individual's data, and
      this information was used to predict inter-individual differences in lung
      particle burdens at given exposures. The influence of smoking history, race and
      pulmonary fibrosis on the individual's estimated clearance parameters was also
      evaluated. RESULTS: The model structure that provided the best fit to these coal
      miner data includes a first-order interstitialization process and no dose
      dependent decline in alveolar clearance. The parameter that had the largest
      influence on model output is fractional deposition. Race and fibrosis severity
      category were statistically significant predictors of individual's estimated
      alveolar clearance rate coefficients (P < 0.03 and P < 0.01-0.06, respectively),
      but smoking history (ever, never) was not (P < 0.4). Adjustments for these group
      differences provided some improvement in the dosimetry model fit (up to 25%
      reduction in the mean squared error), although unexplained inter-individual
      differences made up the largest source of variability. Lung burdens were
      inversely associated with the miners' estimated clearance parameters, e.g.
      individuals with slower estimated clearance had higher observed lung burdens.
      CONCLUSIONS: The methods described in this study were used to examine issues of
      uncertainty in the model structure and variability of the miners' estimated
      clearance parameters. Estimated individual clearance had a large influence on
      predicted lung burden, which would also affect disease risk. These findings are
      useful for risk assessment, by providing estimates of the distribution of lung
      burdens expected under given exposure conditions.

PMID- 11453307
TI  - Quality adjusted life years (QALYs) and dose-response models in environmental
      health policy analysis -- methodological considerations.
AB  - Analyses of competing risks are currently limited by the lack of empirically well
      founded and generalizable quantitative methods. Specifically, quantitative
      methods for comparative risk analysis require the consideration of the population
      impacted, the duration of impact, the health endpoints at risk, and the impact on
      individual quality of life. Whereas risk analysis can be used to provide
      quantitative estimates of disease incidence, environmental health policy analyses
      do not often account for differences in health impact from alternative disease
      states. We discuss the methodological issues related to the use of quality
      adjusted life years (QALY) as a metric for normalizing expected disease incidence
      to account for health impact. Through a case study of the risks and benefits of
      fish consumption, we demonstrate the use of QALY weights with dose-response
      models for environmental health policy decision making. We suggest that, although
      this approach can be generalized for use in comparative risk and health policy
      analysis, it is informationally intensive and requires additional assumptions to
      those used in traditional safety/risk assessment.

PMID- 11453308
TI  - Ethnic and genetic differences in metabolism genes and risk of toxicity and
      cancer.
AB  - Individual risk of toxicity or cancer can be affected by one's exposure to
      sufficiently high doses of particular environmental agents (or mixtures),
      combined with each person's underlying genetic predisposition. The development of
      unequivocal DNA tests for genetic susceptibility to toxicity and cancer and the
      identification of individuals at increased risk, would revolutionize the fields
      of public health and preventive medicine. A growing number of human genetic
      polymorphisms in drug-metabolizing enzymes (DMEs) and the receptors controlling
      DME expression, are being characterized, some of these have been shown to be
      correlated with risk of toxicity or cancer, whereas, others presently remain
      equivocal and require further study. 'Phase I' DMEs, many of which represent
      cytochromes P450, sometimes metabolically activate pro-carcinogens to genotoxic
      electrophilic intermediates and other times are involved in detoxification.
      'Phase II' DMEs are sometimes activating, but usually they conjugate Phase I
      intermediates to water-soluble derivatives, to complete the detoxification cycle.
      Genetic differences in the regulation, expression and activity of genes coding
      for Phase I and Phase II DMEs and DME receptors that control DME activity levels,
      can be crucial factors in defining cancer susceptibility and the toxic or
      carcinogenic power of environmental chemicals. In this review, our current
      knowledge about polymorphisms in several of these genes is summarized.

PMID- 11453309
TI  - Measurement and treatment of dyspnoea.

PMID- 11453310
TI  - Haemoptysis: aetiology, evaluation and outcome--a prospective study in a third
      world country.
AB  - Haemoptysis is an alarming symptom, and the management depends upon the
      aetiology. Emergency management depends upon localization of the site of bleeding
      by roentgenogram, computerized chest tompgraphy and bronchoscopy. We
      prospectively evaluated 52 patients with haemoptysis admitted to the Chest
      Hospital, Kuwait for 1 year (January 1998 to December 1998) and followed them up
      for 1 year (January 1999 to December 1999). There were 42 males (80.8%) and 10
      (19.2%) females, with a mean age of 42.2 (16-86) years. Of these, 26.9% were
      Kuwaiti nationals, 36.5% were Arab non-Kuwaiti nationals, 34.6% were Asians and
      1.9% were other nationals. The aetiologies of haemoptysis were bronchiectasis
      (21.2%), old pulmonary tuberculosis with bronchiectasis (17.3%), active pulmonary
      tuberculosis (15.4%), bronchitis (5.8%), aspergilloma, rheumatic heart disease
      and carcinoid (1.9%). Aetiology could not be identified in 25% of patients. The
      site of bleeding in haemoptysis could not be localized by the consultants in 18
      (32%) by roentgenogram. 16 patients (37%) by CT scan and 23 patients (50%) by
      Fibreoptic bronchoscopy. Sequential estimation of hemoglobin showed a mean of
      13.56 (SD 1.9) and 13.31 (SD 1.8) after 24 h. The difference in mean was
      statistically significant (p<0.036). Conservative management was given in 80.8%,
      and embolotherapy or surgical intervention in 19.2% of patients. Only 12% of
      patients had recurrent haemoptysis at 1-year follow up. In conclusion,
      bronchiectasis and pulmonary tuberculosis were the major causes of haemoptysis in
      this study. Roentgenogram, CT scan and fibreoptic bronchoscopy are useful for
      localizing the site of bleeding. Sequential estimation of haemoglobin may be
      helpful in assessing the severity of haemoptysis, but larger studies are required
      to address this observation. The outcome of haemoptysis is generally good, with a
      low mortality and recurrence rate.

PMID- 11453311
TI  - The efficacy and safety of two oral moxifloxacin regimens compared to oral
      clarithromycin in the treatment of community-acquired pneumonia.
AB  - An international multi-centre, randomized, prospective, double-blind study
      compared oral moxifloxacin (200 mg or 400 mg once daily for 10 days) with oral
      clarithromycin (500 mg, twice daily for 10 days) in the treatment of community
      acquired pneumonia (CAP). The clinical success rate in the evaluable population
      at the primary efficacy assessment, 3-5 days after the end of study treatment,
      was 93.9% in patients treated with 200 mg moxifloxacin; 94.4%, with 400 mg
      moxifloxacin; and 94.3%, with clarithromycin. Clinical success rates were
      maintained at follow-up, 21-28 days after the end of treatment: 90.7% (200 mg
      moxifloxacin), 92.8% (400 mg moxifloxacin) and 92.2% (clarithromycin). The 95%
      confidence intervals indicated that all three treatment regimens were equally
      effective in treating CAP. At follow-up, the 400 mg moxifloxacin dose had a
      slightly higher observed cure rate than the 200 mg moxifloxacin dose, but this
      was not statistically significant. The most frequently isolated pathogens were
      Streptococcus pneumoniae (42%), Haemophilus influenzae (19%), Haemophilus
      parainfluenzae (10%), Moraxella catarrhalis (6%), Klebsiella pneumoniae (5%) and
      Staphylococcus aureus (4%). The bacteriological success rate (eradication and
      presumed eradication) was 72.5% (29/40) for 200 mg moxifloxacin, 78.7% (37/47)
      for 400 mg moxifloxacin and 70.7% (29/41) for clarithromycin. The adverse event
      profile was comparable between the three treatment groups. Most adverse events,
      possibly or probably related to the study drug, were generally mild or moderate
      in severity and mostly related to the digestive system: diarrhoea, nausea and
      abdominal pain in 200 mg moxifloxacin patients; diarrhoea, liver function
      abnormalities and nausea in 400 mg moxifloxacin patients and liver function
      abnormalities, diarrhoea, nausea and taste perversion in clarithromycin patients.
      Study drugs were discontinued because of adverse events in 7/229 (3%) patients
      treated with 200 mg moxifloxacin, 11/224 (5%) with moxifloxacin 400 mg and 11/222
      (5%) with clarithromycin. In all assessments, moxifloxacin was at least as
      effective clinically, and as well tolerated as clarithromycin in the treatment of
      CAP. Bacteriological success rates in moxifloxacin-treated patients were greater
      than those of clarithromycin. Moxifloxacin, given once daily, is free of many
      drug-drug interactions and requires no dosage adjustments in most renal hepatic
      deficient patients.

PMID- 11453312
TI  - Effect of inhaled budesonide therapy on lung function in schoolchildren born
      preterm.
AB  - We investigated the effect of inhaled glucocorticoid (GC) on bronchial
      obstruction and on bronchial lability in schoolchildren born preterm. Twenty-one
      children with bronchial obstruction, increased responsiveness to a beta2-agonist,
      and/or increased diurnal variation in peak expiratory flow (PEF) were selected
      for an open longitudinal study of the value of inhaled GC. None of these children
      had an earlier diagnosis of asthma or current GC treatment. Eighteen children
      with median (range) birth weight 1025 (640-1600) g and gestational age 28 (24-35)
      weeks, age at study 10.1 (7.7-13) years, were treated with inhaled budesonide in
      initially high (0.8 mg m(-2) day(-1) for 1 month) and subsequently lower dose
      (0.4 mg m(-2) day(-1) for 3 months). Daily symptom scores were recorded.
      Spirometric values were measured in the clinic at the beginning and end of each
      treatment period. At home, children used a data storage spirometer. After
      treatment with budesonide for 4 months, spirometric values in the clinic did not
      significantly change. The median forced expiratory volume in 1 sec (FEV1) was 74%
      of predicted both at entry and after budesonide treatment. However, the median
      number of > or = 20% diurnal change in PEF values at home decreased during
      treatment. According to the present study, inhaled budesonide for 4 months had no
      significant effect on basic lung function but may decrease bronchial lability in
      schoolchildren born preterm.

PMID- 11453313
TI  - Can asthma treatment in sports be doping? The effect of the rapid onset, long
      acting inhaled beta2-agonist formoterol upon endurance performance in healthy
      well-trained athletes.
AB  - Inhaled beta2-agonists have been subject to restrictions in relationship to
      sports due to fear of possible improvement in endurance performance. According to
      the international doping regulations only inhaled salbutamol, terbutaline and
      salmeterol are allowed for use in sports. Formoterol is a recently introduced
      rapid onset-long-acting inhaled beta2-agonist. The main aim of the present
      randomized, double-blind placebo-controlled study was to investigate possible
      improvement in endurance performance of inhaled formoterol in 24 healthy well
      trained competitive male athletes, 21-29 years old. Lung function (flow-volume
      loops) was measured before, 15 min after each inhaled study drug and before and
      repeatedly after exercise. On day 1, maximum oxygen uptake (VO2max), peak
      ventilation (VEpeak) and running time till exhaustion were measured and used to
      determine the exercise load on days 2 and 3. On days 2 and 3 the subjects inhaled
      the study drugs, rested for 1 h, then exercised, and VO2max, VEpeak and running
      time until exhaustion were determined. Inhaled formoterol did not improve any
      parameter of endurance performance. On the other hand a statistically
      significant, although not clinically significant (0.05 ml(-1) min kg(-1)), change
      was found in estimated difference of VO2max between formoterol and placebo in
      favour of placebo. Lung function increased significantly after inhaled
      formoterol, and after exercise also for placebo, but without differences between
      the beta2-agonist and placebo after exercise. In conclusion, inhaled formoterol
      did not improve endurance performance compared to placebo.

PMID- 11453314
TI  - Cytokines in pleural liquid for diagnosis of tuberculous pleurisy.
AB  - An elevated level of adenosine deaminase (ADA) in pleural liquid has been
      considered as a supplemental diagnostic marker for tuberculous pleurisy. However,
      this is complicated by false-positives and -negatives. Recently, it has been
      revealed that various cytokines are intimately involved in the pathognomonic
      physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis
      factor alpha (TNFalpha) and interferon gamma (IFNgamma) were compared with ADA in
      pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and
      tuberculous (21 cases) disease. The pleural ADA, IL-8, TNFalpha and IFNgamma
      levels in the tuberculous group were higher than in the other three groups.
      Analysis of receiver operating characteristic (ROC) curves, to evaluate the
      utility of the various parameters, demonstrates values for the area under the
      curve (AUC) of 0.770, 0.875, 0.892 and 0.987, respectively for IL-8, TNFalpha,
      ADA and IFNgamma. No false-positives were encountered with IFNgamma and only one
      case with a small volume of pleural liquid was a false-negative. This indicates
      that IFNgamma is a very reliable marker of tuberculous pleurisy.

PMID- 11453315
TI  - An evaluation of short-term oxygen therapy: the prescription of oxygen to
      patients with chronic lung disease hypoxic at discharge from hospital.
AB  - The provision of domiciliary oxygen to patients hypoxic at hospital discharge has
      been termed short-term oxygen therapy (STOT). This practice appears widespread,
      although there is a paucity of literature and no evidence-based guidelines. We
      undertook this audit to examine the prescription of STOT and determine the
      proportion fulfilling for long-term oxygen therapy (LTOT) 2 months post
      discharge. STOT was defined prospectively: resting PaO2 < or = 7.3 kPa (55 mmHg)
      or PaO2 between 7.3 and 8.0 kPa (60 mmHg) with any of the following: clinical
      evidence of cor pulmonale (pedal oedema or jugular venous distension), ECG
      evidence of pulmonale, echocardiogram evidence of pulmonary hypertension,
      haematocrit > 0.55 (adapted directly from LTOT criteria). Patients were evaluated
      for LTOT 2 months post-discharge when clinically stable on optimal medical
      management. All referrals to the Auckland Regional Oxygen Service between July
      1998 and 1999 were systematically reviewed. The majority 289/405 (71%) of new
      referrals were for the prescription of STOT/LTOT in patients with chronic lung
      disease: 160/289 (55%) derived from hospitalized patients with the majority 130
      (81%) fulfilling criteria for STOT, median age 73, range 24-96 years. Mean
      hospital stay was 10.2 days. Two months after discharge 22/127 (17%) of STOT
      patients had died, comparable with 4/22 (18%) not fulfilling criteria for STOT. A
      total of 123 patients were assessed for LTOT at 2 months; 76 (62%) fulfilled
      criteria for LTOT. The prescription of oxygen at hospital discharge represented a
      considerable proportion of our referral load. There was a high mortality in the 2
      month follow-up period. A significant proportion of STOT patients did not
      subsequently fulfill criteria for LTOT. Further prospective studies are required
      in order to develop evidence-based guidelines.

PMID- 11453316
TI  - p53, p21 and metallothionein immunoreactivities in patients with malignant
      pleural mesothelioma: correlations with the epidemiological features and
      prognosis of mesotheliomas with environmental asbestos exposure.
AB  - The aim of this study is to investigate immunoreactivity for p53, p21 and
      metallothionein in diffuse malignant pleural mesothelioma (DMPM) and to determine
      the relationships between the age, sex, asbestos exposure time, survival of DMPM
      patients with environmental asbestos exposure and immunoreactivity to p53, p21
      and metallothionein. Sixty-seven histopathologically-confirmed DMPMs, 38 of whom
      had environmental and 29 had occupational asbestos exposure, were included. The
      tumour tissue samples were immunostained with antibodies against p53, p21 and
      metallothionein. Epidemiological data and the survival times for the DMPM
      patients with environmental asbestos exposures were obtained from hospital
      records. Thirty-three per cent of the DMPMs were positive for p53, 35% for p21
      and 52% for metallothionein. There was no statistical difference between the
      histological subtypes of DMPM in terms of immunoreactivity for p53, p21 and
      metallothionein. For p21 and metallothionein there was a statistically
      significant difference between the exposure characteristics: patients with
      environmental asbestos exposure had shown more immunopositivity. There were
      statistically significant differences between age groups and between asbestos
      exposure times for metallothionein, and between asbestos exposure times and p21.
      The patients with positive immunostaining had longer exposure times and were
      older than those having negative immunostaining. The differences between survival
      of the patients were not statistically significant in terms of the
      immunohistochemical results for p53, p21 and metallothionein.

PMID- 11453317
TI  - Comparison of the effects of sleep deprivation, alcohol and obstructive sleep
      apnoea (OSA) on simulated steering performance.
AB  - Patients with obstructive sleep apnoea (OSA) are reported to have an increased
      risk of road traffic accidents. This study examines the nature of the impairment
      during simulated steering in patients with OSA, compared to normal subjects
      following either sleep deprivation or alcohol ingestion. Twenty-six patients with
      OSA and 12 normal subjects, either deprived of one night's sleep or following
      alcohol ingestion [mean (SD) alcohol blood level 71.6 mg dl(-1) (19.6)],
      performed a simulated steering task for a total of 90 min. Performance was
      measured using the tendency to wander (SD), deterioration across the task, number
      of 'off-road' events and the reaction time to peripheral events. Control data for
      OSA, sleep deprivation and alcohol were obtained following treatment with nasal
      continuous positive airway pressure (nCPAP), after a normal night of sleep, and
      following no alcohol, respectively. Patients with untreated OSA, and sleep
      deprived or alcohol-intoxicated normal subjects performed significantly less
      well, compared to their respective controls (P<0.01 for all tests), with
      untreated OSA lying between that of alcohol intoxication and sleep deprivation.
      Alcohol impaired steering error equally throughout the whole drive, whilst sleep
      deprivation caused progressive deterioration through the drive, but not
      initially. Untreated OSA was more like sleep deprivation than alcohol, although
      there was a wide spread of data. This suggests that the driving impairment in
      patients with OSA is more compatible with sleep deprivation or fragmentation as
      the cause, rather than abnormal cognitive or motor skills.

PMID- 11453318
TI  - Association of oral almitrine and medroxyprogesterone acetate: effect on arterial
      blood gases in chronic obstructive pulmonary disease.
AB  - Almitrine (A) and medroxyprogesterone acetate (MA) given separately improve
      arterial blood gases in some patients with chronic obstructive pulmonary disease
      (COPD); the aim of this study was to assess the effect of the two drugs given
      together. Forty-eight patients with irreversible COPD and hypoxaemia were
      prospectively enrolled into a 14-day run-in period and received single-blind oral
      treatment with double placebo. Patients whose PaO2 remained stable (less than 10%
      change; n = 29, 25 males, mean age 65.6 years) were included in a 14-day active
      treatment period and randomly assigned to three groups. They received double
      blind oral treatment with: A (50 mg bid, group A, n = 10); MA (20 mg tid, group
      MA, n = 9); A (50 mg bid) and MA (20 mg tid, group A+MA, n = 10). Anthropometric
      and spirometric measurements were similar in the three groups and so were the
      arterial blood gas values at the beginning and the end of the run-in period. At
      the end of the active treatment period, blood gas changes (mean+/-SE) were
      significantly different between groups (P<0.05, Kruskal-Wallis test), with
      improvement in both hypoxaemia and hypercapnia in group A+MA only: delta PaO2 =
      7.4+/-1.9 mmHg, delta PaCO2 = -5.1+/-1.7 m mHg (P<0.05, Wilcoxon test). In short
      term treatment, the association of A and MA is more efficient than either drug
      alone at improving arterial blood gases in COPD patients.

PMID- 11453319
TI  - The role of outdoor air pollution and climatic changes on the rising trends in
      respiratory allergy.
AB  - Evidence suggests that allergic respiratory diseases such as hay fever and
      bronchial asthma have become more common world-wide in the last two decades, and
      the reasons for this increase are still largely unknown. A major responsible
      factor could be outdoor air pollution, derived from cars and other vehicles.
      Studies have demonstrated that urbanization and high levels of vehicle emissions
      and westernized lifestyle is correlated with the increasing frequency of pollen
      induced respiratory allergy. People who live in urban areas tend to be more
      affected by pollen-induced respiratory allergy than those from of rural areas.
      Pollen allergy has been one of the most frequent models used to study the
      interrelationship between air pollution and respiratory allergic diseases. Pollen
      grains or plant-derived paucimicronic components carry allergens that can produce
      allergic symptoms. They may also interact with air pollution (particulate matter,
      ozone) in producing these effects. There is evidence that air pollutants may
      promote airway sensitization by modulating the allergenicity of airborne
      allergens. Furthermore, airway mucosal damage and impaired mucociliary clearance
      induced by air pollution may facilitate the access of inhaled allergens to the
      cells of the immune system. In addition, vegetation reacts with air pollution and
      environmental conditions and influence the plant allergenicity. Several factors
      influence this interaction, including type of air pollutants, plant species,
      nutrient balance, climatic factors, degree of airway sensitization and
      hyperresponsiveness of exposed subjects.

PMID- 11453320
TI  - A comparison of surfactant delivery with conventional mechanical ventilation and
      partial liquid ventilation in meconium aspiration injury.
AB  - The objective of this study was to compare surfactant (SF) distribution and
      physiological effects after standard SF delivery during conventional mechanical
      ventilation (CMV) with that using partial liquid ventilation (PLV). A model of
      meconium aspiration syndrome (MAS) was developed using two groups of adult rats
      (n = 14). After meconium instillation of 2.5 ml kg(-1) (20% v/w), SF/CMV: (n = 7)
      CMV and SF/PLV: (n = 7) PLV, received 14C-labeled surfactant (4 ml kg(-1))
      delivered intratracheally in four aliquots over 20 min in both groups. Sequential
      measurements of arterial blood chemistry and lung mechanics were performed in all
      animals. At the conclusion of experiments, lungs were inflated (30 cmH2O), dried,
      sectioned and evaluated for radioactivity in disintegrations per minute (DPM).
      Surfactant distribution was improved (P< 0.01) with PLV as compared to CMV with
      48.8% of the pieces vs. 30.9% of the pieces receiving within 25% of the mean
      amount of surfactant, respectively. Further, regional distribution was also
      significantly more uniform with PLV than CMV: left vs right (P<0.01) lung and
      ventral vs. dorsal (P<0.01) regions. Finally, arterial PO2 and ventilation
      efficiency index were significantly (P<0.01) greater post-treatment in SF/PLV
      than SF/CMV. These data demonstrate surfactant delivery with PLV, as compared to
      CMV alone, to be an improved method of delivering surfactant in MAS and suggest
      the possible utility of SF/PLV combination therapy for its treatment of other
      etiologies of neonatal respiratory distress.

PMID- 11453321
TI  - The body weight-walking distance product as related to lung function, anaerobic
      threshold and peak VO2 in COPD patients.
AB  - The product of walking distance and body weight (D x W) mimics the work of
      walking. We hypothesized the superiority of D x W to walking distance (D) alone
      in any correlation with lung function, anaerobic threshold (AT) and maximal
      oxygen uptake (VO2max). We further hypothesized that the D x W product for a 6
      min walk test (6 MWT) would correlate with the AT and VO2max because all three
      are markers of exercise ability. Thirty-three male chronic obstructive pulmonary
      disease (COPD) patients with mean forced expiratory volume in 1 sec (FEV1) of
      1.2+/-0.4 l (range 0.58-1.86 l) were enrolled. Six patients were excluded due to
      inability to achieve a maximal test. Lung function and self-assessed every-day
      activities using a oxygen-cost diagram were evaluated before entry of the study.
      A maximal effort ramp-pattern cardiopulmonary exercise test (CPET) and a 6 MWT
      were conducted in random order. Borg score, heart rate, and O2 saturation with
      pulse oximetry (SpO2) were measured during both exercise tests. VO2 AT and minute
      ventilation were also measured during the CPET. Correlations were sought between
      the distance covered in the 6 MWT, and the D x W product with AT, VO2max and
      other variables. The average D and D x W were 456 m and 27.5 kg km(-1),
      respectively. D x W was superior to D alone when correlated with the VO2max and
      AT determined from the CPET, while modestly correlated with the change (delta) in
      Borg score and delta SpO2 in the 6 MWT and self-assessed every-day activities.
      Distance x weight product was correlated with the AT and VO2max. In addition, D x
      W was better correlated with diffusing capacity for carbon monoxide and vital
      capacity than D alone. We conclude that D x W mimics the work of walking better
      than D and is suggested as a parameter for evaluation of patients' fitness if gas
      exchange measurements are not available.

PMID- 11453322
TI  - Obesity: definitely a growing concern.

PMID- 11453323
TI  - Priorities in polycystic ovary syndrome.

PMID- 11453324
TI  - Containing the costs of managing hypertension.

PMID- 11453325
TI  - Usable written information for patients.

PMID- 11453326
TI  - Investment and performance monitoring in Australian health and medical research.

PMID- 11453327
TI  - Prevalence of overweight and obesity in Australian children and adolescents:
      reassessment of 1985 and 1995 data against new standard international
      definitions.
AB  - OBJECTIVE: To review the prevalence of overweight and obesity in Australian
      children and adolescents in two national samples, 10 years apart, using the new
      standard international definitions of the International Obesity Task Force
      Childhood Obesity Working Group. DESIGN: Body mass index (BMI) cut-off points
      defining overweight and obesity were applied to the individual BMI values in the
      two cross-sectional samples. SETTING: Australian community. PARTICIPANTS: 8,492
      schoolchildren aged 7-15 years (Australian Health and Fitness Survey, 1985) and
      2,962 children aged 2-18 years (National Nutrition Survey, 1995). MAIN OUTCOME
      MEASURE: Prevalence of overweight and obesity. RESULTS: In the 1985 sample, 9.3%
      of boys and 10.6% of girls were overweight and a further 1.7% [corrected] of boys
      and 1.6% [corrected] of girls were obese. In the 1995 sample, overall 15.0% of
      boys (varied with age from 10.4% to 20.0%) and 15.8% of girls (varied with age
      from 14.5% to 17.2%) were overweight, and a further 4.5% of boys (2.4%-6.8%) and
      5.3% of girls (4.2%-6.3%) were obese. The prevalence of overweight and obesity in
      the 1995 sample peaked at 12-15 years in boys and 7-11 years in girls. In
      schoolchildren aged 7-15 years, the rates represent a relative risk of overweight
      in 1995 compared with 1985 of 1.79 (95% CI, 1.59-2.00) and of obesity of 3.28
      (95% CI, 2.51-4.29). Compared with previous estimates from these samples, the
      revised prevalence data are slightly higher for the 1985 data and considerably
      higher for the 1995 data. CONCLUSION: The secular trend of increasing overweight
      and obesity in the decade from 1985 and the high prevalence rates in Australian
      children and adolescents are a major public health concern.

PMID- 11453328
TI  - PBS/RPBS cost implications of trends and guideline recommendations in the
      pharmacological management of hypertension in Australia, 1994-1998.
AB  - OBJECTIVES: To determine the extent to which "current guidelines" for the
      management of hypertension are reflected in the prescribing of antihypertensive
      drugs in Australia over the period 1994-1998, and to examine the cost
      implications of actual and recommended prescribing patterns. DESIGN: Federal
      Government and consumer cost estimates modelled on prescribing patterns and
      guideline recommendations over the period 1994-1998. SETTING: Prescribing on
      Federal Government pharmaceutical schemes over the 1994-1998 period. MAIN OUTCOME
      MEASURES: Estimates of Pharmaceutical Benefits Scheme/Repatriation Pharmaceutical
      Benefits Scheme cost changes in Australian dollar values. RESULTS: The
      implementation of current guidelines for patients with uncomplicated hypertension
      taking monotherapy alone could have reduced drug costs by $45-$108 million in
      1998. CONCLUSIONS: Current prescribing patterns indicate that clinical practice
      has pre-empted the results from clinical trials of newer, more expensive agents
      and that clinicians' prescribing patterns do not closely reflect current
      recommendations.

PMID- 11453329
TI  - Assessing the risk of tuberculosis infection among healthcare workers: the
      Melbourne Mantoux Study. Melbourne Mantoux Study Group.
AB  - OBJECTIVE: To determine the potential prevalence of nosocomial infection with
      Mycobacterium tuberculosis among hospital employees in teaching hospitals in
      Melbourne. DESIGN: Cross-sectional survey of positive tuberculin skin test
      (Mantoux) responses among employees in 14 public hospitals in Melbourne, January
      1996 to April 1999. PARTICIPANTS: All consenting employees in participating
      hospitals (4,070 healthcare and 4,298 non-healthcare workers; participation
      rates, 13%-66%). OUTCOME MEASURES: Prevalence of positive responses to tuberculin
      skin tests among healthcare and non-healthcare workers and association with
      employee and hospital characteristics. RESULTS: Healthcare workers were
      significantly more likely to have a positive tuberculin response than non
      healthcare workers (19.3% versus 13.7%; odds ratio, 1.5; 95% CI, 1.3-1.7;
      P<0.001). Multivariable analysis revealed that age, country of birth (high versus
      low tuberculosis [TB] prevalence), history of BCG (bacille Calmette-Guerin)
      vaccination, years since last BCG, occupation (healthcare versus non-healthcare
      worker) and years of hospital employment were all significantly associated with a
      positive response. Rates of positive responses among employees varied greatly
      between hospitals (6%-35%). These differences were not explained by employee
      characteristics, hospital TB patient load (number of admissions or bed-days) or
      percentage of hospital patients from countries with high TB prevalence. The
      hospital with the highest rate of positive responses was notable for its lack of
      negative-pressure isolation rooms for TB patients. CONCLUSIONS: Positive
      tuberculin responses are relatively common among hospital employees in Melbourne,
      with rates varying between hospitals and being higher among healthcare than non
      healthcare workers. Employee characteristics, such as age, country of birth and
      past BCG status, explain little of this variation. More emphasis on TB infection
      control measures and regular staff screening may be needed.

PMID- 11453330
TI  - Readability and content of supplementary written drug information for patients
      used by Australian rheumatologists.
AB  - OBJECTIVE: To determine the readability and content of supplementary written drug
      information currently being given to patients by rheumatologists in Australia.
      DESIGN AND PARTICIPANTS: Blinded standardised review by two independent reviewers
      of supplementary written drug information routinely provided to patients by the
      195 fully registered members of the Australian Rheumatology Association (ARA).
      MAIN OUTCOME MEASURES: FOG and SMOG readability scores to estimate readability;
      critical appraisal of content according to predetermined criteria. RESULTS: 84
      rheumatologists responded (43%), 45 of whom reported providing copies of written
      drug information to patients. Overall, 91 different documents were reviewed.
      Drugs most commonly considered were methotrexate (17), gold (16), sulfasalazine
      (10), penicillamine (10) and prednisolone (8). Level of agreement between
      reviewers for FOG and SMOG scores was fair to good (intraclass correlation
      coefficient, 0.61 and 0.51, respectively). Mean (95% CI) FOG and SMOG scores were
      12.6 (12.2-12.9) and 11 (10.7-11.2), respectively (implying that half of those in
      Year 12 [or aged 17 years] and Year 11 [or aged 16 years] according to the FOG
      and SMOG mean scores, respectively, will comprehend half of the text or more).
      For the same medication, there was a wide variation in the information provided,
      including which side effects were discussed. While 98% included some information
      about side effects, fewer considered dose (74%), drug interactions if applicable
      (70%), purpose of drug (67%), how and when to take the drug (62%), expected time
      to improvement (54%), what to do in the event of side effects (44%), the expected
      duration of therapy (18%) and what to do if a dose was missed (5%). CONCLUSIONS:
      The reading level required to understand supplementary written drug information
      used by Australian rheumatologists is much higher than the average reading
      ability of the Australian population (estimated at Year 8 level). The content of
      this information varies widely and often omits important information.

PMID- 11453331
TI  - Metformin and intervention in polycystic ovary syndrome. Endocrine Society of
      Australia, the Australian Diabetes Society and the Australian Paediatric
      Endocrine Group.
AB  - Polycystic ovary syndrome (PCOS) is classically characterised by ovarian
      dysfunction (oligomenorrhoea, anovulation and infertility), androgen excess
      (hirsutism and acne), obesity, and morphological abnormalities of the ovaries
      (cystic enlargement and stromal expansion). More recently, insulin resistance has
      been found to be common in PCOS, along with an increased prevalence of other
      features of the "metabolic syndrome", namely glucose intolerance, type 2 diabetes
      mellitus, and hyperlipidaemia. Hyperinsulinaemia is likely to contribute to the
      disordered ovarian function and androgen excess of PCOS. Reducing insulin
      resistance by lifestyle modifications such as diet and exercise improves
      endocrine and menstrual function in PCOS. These lifestyle modifications are the
      best initial means of improving insulin resistance. Metformin, an oral
      hypoglycaemic agent that increases insulin sensitivity, has been shown to reduce
      serum concentrations of insulin and androgens, to reduce hirsutism, and to
      improve ovulation rates. The effect of metformin alone on fertility rates is
      unknown. Some studies suggest that metformin will reduce total body weight to a
      small extent, but with a predominant effect on visceral adipose reduction. The
      effects of metformin on lipid abnormalities, hypertension or premature vascular
      disease are unknown, but the relative safety, moderate cost, and efficacy in
      reducing insulin resistance suggest that metformin may prove to be of benefit in
      combating these components of the "metabolic" syndrome in PCOS. Further properly
      planned randomised controlled trials are required.

PMID- 11453332
TI  - EBM in practice: paediatrics.
AB  - There is a substantial gap between what we "need to know" and what we "actually
      know" to practise evidence-based paediatrics. Good evidence from primary research
      studies about effective child healthcare strategies (for individuals or
      populations) for a broad range of important issues is lacking. Systematic reviews
      of existing good-quality research evidence, or evidence-based clinical practice
      guidelines relevant to child health, are often not readily available or
      accessible to practising clinicians. Recent initiatives to supply the information
      needs of paediatricians should lead to improvements in the availability,
      accessibility and applicability of the "evidence-base". These efforts need wider
      commitment and further resources. The gap between what we already "know" and what
      we "actually do" in daily practice is even wider. We need to improve our efforts
      to implement existing research knowledge, using strategies with demonstrated
      effectiveness, to promote the timely transfer of research evidence into actual
      practice. The health outcomes of these efforts need to be systematically
      evaluated.

PMID- 11453333
TI  - Evidence-based obstetrics in Australia: can we put away the wooden spoon?
AB  - In the evidence-based medicine stakes, obstetrics has risen from being the holder
      of the "wooden spoon" to being a world leader in the pursuit of best evidence and
      the use of formal systematic reviews. A prime example of evidence-based obstetric
      practice is the use of corticosteroids to reduce respiratory distress syndrome in
      preterm infants. However, in other areas, such as the rising caesarean section
      rates, providing best evidence to guide practice has proven difficult. The
      availability of evidence has not always resulted in changed clinical practice and
      improved patient care. Researchers in Australia are now examining strategies to
      maximise dissemination of available best evidence into obstetric practice.
      Without reflective practice and effective dissemination of evidence, the present
      litigation phobia surrounding obstetric care could lead to evidence-based
      medicine being replaced by "nervousness-based medicine".

PMID- 11453334
TI  - Losing the battle of the bulge: causes and consequences of increasing obesity.
AB  - Increasing proportions of Australians are overweight or obese, a problem shared
      by all developed and, increasingly, developing nations. Now as many people in the
      world are overweight as underweight. Increasing obesity is a serious public
      health as well as economic problem. Its associated greater risks of high blood
      pressure, heart disease, osteoarthritis, type 2 diabetes, some cancers and other
      health problems consume considerable proportions of healthcare budgets. Health
      inequalities often reflect social inequalities, but with overweight there is also
      a male-female difference in the relationship between overweight and socioeconomic
      status. Health promotion campaigns are underestimating the social determinants of
      health, and "risk fatigue" is affecting attitudes to complying with healthy
      lifestyle standards. Proposals to reverse the obesity trend, such as taxing or
      restricting the advertising of unhealthy foods, raise contentious issues of
      choice and regulation.

PMID- 11453335
TI  - Neuroleptic malignant syndrome: an underdiagnosed condition.

PMID- 11453336
TI  - Cranial and peripheral neuropathies.
AB  - An acute polyneuropathy developing over days to several weeks is most likely to
      be Guillain-Barre syndrome or a toxic neuropathy, although vasculitis can also
      present acutely. This presentation should be referred immediately for further
      investigation. A subacute to chronic (ie, developing over months) neuropathy with
      significant proximal weakness and prominent loss of reflexes is highly suggestive
      of chronic inflammatory demyelinating polyradiculoneuropathy. If there is a clear
      stepwise onset of symptoms, suggestive of multiple mononeuropathies, or
      significant asymmetry, vasculitic neuropathy should be considered, even in the
      absence of systemic vasculitis. Idiopathic chronic axonal neuropathy is an
      indolent, predominantly sensory neuropathy that typically occurs in older
      patients. Neuropathies occurring in young or middle age or with more subacute
      onset always warrant further investigation.

PMID- 11453337
TI  - Strychnine, ammonia and gunpowder for snakebite--the end of an era.

PMID- 11453338
TI  - Supraglottic dystonic reaction to metoclopramide in a child.

PMID- 11453339
TI  - Anaphylaxis associated with the same batch of tiger-snake antivenom.

PMID- 11453340
TI  - Normocholesterolaemic dyslipidaemia: is there a role for fibrates?

PMID- 11453341
TI  - Normocholesterolaemic dysslipidaemia: is there a role for fibrates?

PMID- 11453342
TI  - A primer of complementary and alternative medicine commonly used by cancer
      patients.

PMID- 11453343
TI  - Quality and the art of medicine.

PMID- 11453344
TI  - Changes in the use of hormone replacement therapy in New Zealand from 1991-1997.
AB  - AIMS: To describe changes in the prevalence of hormone replacement therapy (HRT)
      use in New Zealand women aged 45-64 years from 1991-1997. METHODS: For each of
      two population-based surveys, 2,000 women aged 45-64 years were randomly selected
      from the electoral roll and sent questionnaires. The response rates were 78% in
      1991 and 73% in 1997. RESULTS: Current use of HRT increased from 12% in 1991 to
      20% in 1997 (OR=2.0, 95% CI (1.6, 2.4)). In both surveys, professional women or
      those with husbands in professional occupations were more likely to use HRT.
      Women in all socio-economic and educational groups experienced a two fold
      increase in the use of HRT from 1991 to 1997. The majority started HRT primarily
      or partly for relief of symptoms (85% in 1991, 83% in 1997). While almost half
      had started it to prevent osteoporosis in both surveys, there was a marked
      increase between 1991 and 1997 in the proportion of women who had started it to
      prevent coronary heart disease (13% in 1991, 25% in 1997, p=0.0002). In each
      survey, just over a quarter of women had undergone a hysterectomy and they were 2
      3 times more likely to be using HRT than other women. CONCLUSIONS: In New Zealand
      the prevalence of HRT use has doubled in the 1990s, despite uncertainties about
      the magnitude of benefits and risks of its long-term use.

PMID- 11453345
TI  - Review of total hip replacement. The Middlemore Hospital experience, 1980-1991.
AB  - AIM: To determine the outcome of 1951 total hip arthroplasties performed between
      1980 and 1991 at Middlemore Hospital. METHODS: An independent retrospective
      review was carried out between 1993 to 1995 giving a minimum follow-up of two
      years. Useable data were obtained for 96.8% of cases. RESULTS: The overall wound
      infection rate was 3.4% (n=65), and of these seven (10.8%) required revision. The
      revision rate for infection for all patients was 1.16% (n=22). The in-hospital
      dislocation rate was 2.6% (n=49), and of these five (9.8%) required revision.
      Patient pain, activity and satisfaction were acceptable. Revision was required
      for 163 patients (8.7%), mainly for loosening. A survival analysis of the
      commonly used implants at seven years matched results from other studies. (Stem
      survival: Spectron 99.5%, Charnley 95.6%. Cup survival: Spectron 97.9%, Charnley
      98.1%). Analysis of outcome predictors showed that youth and weight both
      influence the rate of revision. CONCLUSIONS: Results in terms of patient
      satisfaction and revision rates were comparable with other published series. The
      wound infection rate was higher than desirable, but not unexpected in view of the
      number of surgeons involved (73) and the lack of special theatre facilities.

PMID- 11453346
TI  - The health of lone mothers in New Zealand.
AB  - AIMS: To compare the sociodemographic characteristics and the mental and physical
      health status of lone and couple mothers, and to explore possible contributing
      factors to any differential health status identified. METHODS: Data from the
      1996/97 New Zealand Health Survey were analysed. Lone and couple mothers were
      compared according to sociodemographic factors, health risk behaviours and three
      medical conditions. Their self-reported health was measured and compared using
      the SF-36 questionnaire. Multivariate analyses were performed to explore the
      possible contributing factors to any health disadvantage identified. RESULTS:
      Lone mothers (n=721) were more likely to be Maori, to have lower family incomes,
      lower educational qualifications and to live in more deprived areas. There were
      no significant differences between lone and couple mothers in their prevalence of
      probable asthma and diagnosed diabetes mellitus, or in their self-reported
      physical health status after adjustment for socioeconomic variables. However,
      lone mothers had higher rates of ever having been on medication for hypertension
      (OR=2.3; 1.2-4.1), and significantly worse self-reported mental health which
      persisted after adjustment for differences in socioeconomic and other factors.
      CONCLUSIONS: These findings suggest that lone mothers are a vulnerable group and
      special consideration should be given to them if inequalities in health are to be
      addressed.

PMID- 11453347
TI  - Implementation of evidence based cardiovascular risk treatments by general
      practitioners.
AB  - AIM: To review general practitioner (GP) implementation of evidence based
      cardiovascular risk reducing strategies in subjects with coronary heart disease
      (CHD). METHODS: Audit of patient records of randomly selected GPs. RESULTS: There
      were 326 subjects with CHD under the care of 21 doctors. Except for smoking,
      details of lifestyle measures were rarely found in the notes. Advice on diet and
      exercise was mentioned in 51% and 23.3% of records respectively. Aspirin and beta
      blockers were widely used. Of patients with drug untreated values of total
      cholesterol (TC) and/or TC/HDL exceeding National Heart Foundation (NHF)
      guidelines, 71% were prescribed lipid-modifying drugs. NHF targets for TC (< or =
      5.0 mmol/l) were achieved by 37% and for TC/HDL (< or = 4.5) by 60%. TC remained
      above 5.5 mmol/L in 120 cases. Lipid results from tests within the last 12 months
      were found in 60% of cases. CONCLUSIONS: Recording of lifestyle treatments in
      subjects with CHD appears to be assigned low priority. Cardioprotective
      treatments were widely used. Cholesterol levels were recorded frequently and of
      those with values exceeding NHF guidelines, nearly 3/4 were on medication.
      Recommended targets for lipid parameters were being achieved by <50% of patients.
      More frequent monitoring could improve this outcome

PMID- 11453348
TI  - Towards the optimal use of inhaled corticosteroid therapy in adult asthma.

PMID- 11453349
TI  - '...with a song in one ear and a lament in the other...'.

PMID- 11453350
TI  - Viruses to the rescue: p53-based therapies in the fight against cancer.

PMID- 11453351
TI  - Reaching an acceptable standard of practice in  an environment of limited
      resources.

PMID- 11453353
TI  - Professional misconduct.

PMID- 11453352
TI  - Tobacco and taking responsibility.

PMID- 11453354
TI  - And now the failure of cervical screening.

PMID- 11453355
TI  - Hazards associated with the boat building industry in New Zealand.

PMID- 11453356
TI  - Taking risks: primary prevention of cardiovascular events.

PMID- 11453357
TI  - Hazards associated with the boat building industry in New Zealand: an OSH audit.
AB  - AIM: To randomly audit the boat building industry in New Zealand to assess the
      occupational health status and level of knowledge of employees. METHODS: A survey
      was conducted using a nurse and inspector administered questionnaire. 151 workers
      from 120 randomly selected firms participated in the survey. RESULTS: 31.5%
      respondents thought they had had some sort of work related health problem since
      working in that job. 22% reported wheezing during the last twelve months. 14-16%
      met criteria for occupational causation, and 4% met a measure of severe wheezing
      related to work. 25.6% of workers had dermatitis. Only a quarter of these met
      criteria for occupational causation. No respondents reported symptoms suggestive
      of chronic solvent neurotoxicity. Solvents and epoxy resins comprised the
      majority of chemicals with which there was contact. Observation suggested little
      use of Material Safety Data Sheets as a source of knowledge about toxicity of the
      chemicals used. Although 94.3% reported wearing gloves, this did not correlate
      with numbers reporting dermatitis suggesting non-compliance or glove failure.
      CONCLUSION: New Zealand boat builders and their employees remain at risk for
      occupational health problems by virtue of their employment.

PMID- 11453358
TI  - Factors determining non-attendance at a cardiac rehabilitation programme
      following myocardial infarction.
AB  - AIM: To identify factors contributing to patient nonattendance at an outpatient
      cardiac rehabilitation programme following hospital admission for a first
      myocardial infarction. METHODS: Consecutive patients admitted over a two year
      period to the Auckland or Green Lane Hospital Coronary Care Units for a first
      myocardial infarction were identified. All patients had been invited to attend
      the cardiac rehabilitation programme during their admission. A questionnaire was
      mailed to all identified patients. RESULTS: Overall 324 patients were identified
      with a mean age of 61 years, of whom 212 (65%) subsequently attended the cardiac
      rehabilitation programme. 220 of the 324 patients (68%) responded to the
      questionnaire. Univariate analysis revealed that non-attenders were less well
      educated (p <0.05), more often from a lower socioeconomic status (p<0.05) and
      lived alone (p<0.05). Non-attendance and withdrawal from the programme were most
      frequently related to transport and inconvenient scheduling. CONCLUSIONS:
      Patients with less education, lower socioeconomic status and patients living
      alone were less likely to attend a cardiac rehabilitation programme. Provision of
      a transport service and more flexible scheduling of the programme may improve
      attendance.

PMID- 11453359
TI  - Sun protection practices, knowledge and attitudes to tans among New Zealand
      adolescents, 1991-1997.
AB  - AIMS: To examine change in the self-reported sun protection, knowledge and
      attitudes to tans amongst fourth form students from 1991 to 1997. METHODS:
      Questionnaires were mailed to 20 New Zealand secondary schools, where 20 students
      were randomly selected to participate in each school. RESULTS: The proportions of
      adolescents who reported getting sunburnt over summer, and sunbathing for the
      purpose of tanning increased significantly from 1991 to 1997, while there were
      decreases in the proportions who reported getting a suntan, wearing clothing for
      sun protection and having heard of melanoma. There was also some evidence of a
      decrease in the attribution of positive qualities to a tan. CONCLUSIONS: Some
      positive changes in attitudes to tanning among New Zealand adolescents were
      present over the 1991-1997 period. Although these changes are promising there was
      little change in utilisation of sun protection measures, in fact, there was
      evidence that this had worsened.

PMID- 11453360
TI  - Trauma and co-morbidity--a pilot study.
AB  - AIMS: To study the adult trauma patient population at the Auckland Hospital in
      order to determine the age distribution of trauma, the prevalence and importance
      of co-morbid conditions and any effect of the latter on the length of stay in the
      hospital. METHODS: Data were collected on 78 consecutive patients admitted to the
      Auckland Hospital under the Trauma team between December 1999 and January 2000.
      Data were collected by interviewing the patient, as well as reviewing patient's
      medical notes and the Trauma Registry. RESULTS: The prevalence of co-morbidities
      was 14.7%. No co-morbidity was found below the age of 40 years, but the
      prevalence of co-morbidity increased with age. The average length of stay for
      patients with no comorbidities and an Injury Severity Score (ISS) >15 was 19 days
      while for those with co-morbidities was 24.5 days--an increase of 29%.
      CONCLUSION: This pilot study has found that a significant number of trauma
      patients being admitted to Auckland Hospital have a pre-existing co-morbid
      condition that may alter their length of stay. It is an important issue that
      warrants further investigation, in order to devise a more accurate prognostic
      scoring system.

PMID- 11453361
TI  - Pilot study comparing the accuracy of lymphoscintigraphy sentinel lymph node
      localisation with axillary node dissection in women with operable breast cancer.
AB  - AIM: To evaluate the use of lymphoscintigraphy sentinel lymph node mapping with
      scintillation gamma probe detection and blue dye assisted sentinel lymph node
      biopsy in patients with invasive breast cancer. To compare the lymph nodes
      detected lymphosintigraphically and at surgery for invasive breast cancer and the
      accuracy of sentinel node prediction of axillary status. METHODS: A prospective
      pilot study was performed on 36 women diagnosed with invasive breast cancer
      requiring axillary node dissection. Lymphoscintigraphy involving peritumoral
      injection of 99mTechnetium antimony sulphide or rhenium sulphur colloid was
      performed prior to surgery. Sentinel lymph node biopsy was then performed using
      gamma probe and blue dye localisation. RESULTS: Sentinel lymph nodes were
      identified on lymphoscintigrams in 100% of cases, and sentinel nodes located
      surgically in 34/36 (94.4%) of patients. All women with positive axillary lymph
      nodes on axillary dissection were correctly identified on sentinel node biopsy.
      Eight patients demonstrated internal mammary (IM) node radiocolloid uptake, one
      returning positive IM histology in the presence of positive axillary sentinel
      node metastasis. CONCLUSION: A high proportion of sentinel nodes were
      demonstrated by lymphoscintigraphy and were subsequently removed surgically. When
      internal mammary nodes are identified surgical removal should be considered. In
      this small series sentinel lymph node status correctly predicted axillary node
      status in 100% of patients for whom sentinel nodes were retrieved supporting the
      concept of sentinel node biopsy only for women with normal sentinel lymph nodes.
      Evidence from randomised trials that sentinel node based management does not
      compromise regional control of breast cancer or survival, is awaited.

PMID- 11453362
TI  - The Gisborne Inquiry--what can we learn?

PMID- 11453363
TI  - Insulin resistance and type 2 diabetes: time for a new hypothesis.

PMID- 11453365
TI  - Obtaining consent for epidural analgesia for women in labour.

PMID- 11453366
TI  - Health and Disability Commissioner and Gisborne Hospital.

PMID- 11453367
TI  - Dopamine transporter in vitro binding and in vivo imaging in the brain.
AB  - Much research interest has lately been focused on the dopamine transporter
      function in brain. Recent findings indicate that dopamine reuptake is more like a
      highly regulated than a constitutive determinant of dopamine clearance. Positron
      emission tomography (PET) and single-photon emission tomography (SPET) offer
      unique methods to study dopamine transporter function. Results from in vivo PET
      and SPET studies correspond well with in vitro studies performed on post mortem
      human brain tissue. Considering some of the variances between in vitro and in
      vivo receptor binding phenomena it may be that the role of a compound to alter
      binding to monoamine uptake sites in vitro does not indicate its potential to
      affect monoamine transporters after administration in vivo. This discrepancy may
      be better understood taking into account recent studies indicating the
      possibility of a rapid regulation of transporter function and surface expression.
      Furthermore, the dopamine transporter is a fruitful target for CNS drug
      discovery. Fundamental nature of drug actions in vivo may be studied using
      demonstrated in vitro and in vivo imaging methods.

PMID- 11453368
TI  - Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate
      mediated renal oxidative stress and toxicity in Wistar rats.
AB  - In an earlier communication, we have shown that Tephrosia purpurea ameliorates
      benzoyl peroxide-induced oxidative stress in murine skin (Saleem et al. 1999).
      The present study was designed to investigate a chemopreventive efficacy of T
      purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated
      oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N
      diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125
      mg/kg body weight) increases microsomal lipid peroxidation and the activity of
      xanthine oxidase and decreases the activities of renal antioxidant enzymes viz.,
      catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate
      dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase
      and quinone reductase and causes depletion in the level of renal glutathione
      content. A sharp increase in blood urea nitrogen and serum creatinine has also
      been observed. Prophylactic treatment of rats with T. purpurea at doses of 5
      mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine
      initiated and KBrO3 promoted renal oxidative stress and toxicity. The
      susceptibility of renal microsomal membrane for iron ascorbate-induced lipid
      peroxidation and xanthine oxidase activities were significantly reduced (P<0.01).
      The depleted levels of glutathione, the inhibited activities of antioxidant
      enzymes, phase II metabolizing enzymes and the enhanced levels of serum
      creatinine and blood urea nitrogen were recovered to a significant level
      (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data
      indicate that T purpurea besides a skin antioxidant can be a potent
      chemopreventive agent against renal oxidative stress and carcinogenesis induced
      by N-diethylnitrosamine and KBrO3.

PMID- 11453369
TI  - Comparison of the embryotoxic effects of saporin, agrostin (type 1 ribosome
      inactivating proteins) and ricin (a type 2 ribosome-inactivating protein).
AB  - The effects of two type I ribosome-inactivating proteins, saporin and agrostin,
      and the type 2 ribosome-inactivating protein ricin and its constituent A and B
      chains, on the development of cultured mouse embryos, were investigated. Saporin
      and agrostin had similar embryotoxicity which was approximately 10(5) times
      weaker than that of ricin and its A and B chains, and the embryotoxicity of
      saporin and agrostin increased gradually with the dosage. In contrast, there was
      an abrupt rise in embryotoxictiy of ricin-A chain and B chain as the dose was
      raised from 10 to 20 ng x ml(-1). Saporin and agrostin did not affect the heart
      beat and otic placode, but at 10 ng x ml(-1) ricin and 40 ng x ml(-1) ricin-A
      chain and B chain, all of the treated embryos exhibited abnormalities in heart
      beat, yolk sac circulation, body axis, optic placode, otic placode, forelimb
      buds, branchial apparatus and cranial neural tube.

PMID- 11453370
TI  - Inhibition of MAO-A activity enhances behavioural activity of rats assessed using
      water maze and open arena tasks.
AB  - To determine if the inhibition of MAO-A and/or MAO-B activities can influence
      cognitive processes in adult rats, we analysed whether chronic treatment with
      clorgyline, 1-deprenyl and pargyline could modify the performance of adult rats
      in a modified version of the water maze task. The effects of these treatments on
      locomotor activity and enzyme activities were also assessed. Rats were treated
      for 24 days with clorgyline (0.2 mg/kg), 1-deprenyl (0.25 mg/kg) and pargyline (I
      or 10 mg/kg). The treatments were started two weeks before the water maze
      experiment and continued until the end of testing. The rats were trained to find
      a submerged platform (6 days: I trial/day; 7 th day: probe trial). Over the next
      three days, locomotor activity was assessed in an open arena. Treatments with
      clorgyline (MAO-A inhibitor), 1-deprenyl (MAO-B inhibitor) and pargyline (non
      selective MAO inhibitor) did not improve the finding of the hidden platform, when
      compared to treatment with saline, but significantly increased the swimming speed
      of the rats. The different treatments, when compared to saline, failed to modify
      the distance covered and the number of groomings performed in the open arena.
      However, clorgyline and pargyline, 10 mg/kg, increased the number of faecal boli
      and clorgyline enhanced the number of rearings made when compared to saline, 1
      deprenyl and pargyline, 10 mg/kg. These results indicate that near total
      inhibition of MAO-A by clorgyline and pargyline as assessed by MAO activity
      measurement induces an increase in locomotor activity but that inhibition of MAO
      A or MAO-B, either alone or combined, does not facilitate spatial learning in
      adult rats.

PMID- 11453371
TI  - The effect of tumour necrosis factor (TNF) inhibitors in Clostridium difficile
      toxin-induced paw oedema and neutrophil migration.
AB  - Clostridium difficile produces a potent enterotoxin and a cytotoxin, toxin A and
      toxin B, respectively. These toxins are associated with pseudomembranous colitis
      and antibiotic-associated diarrhoea. In the present study, we investigated the
      oedematogenic activity of both toxins, characterizing the time-course and dose
      response of this pro-inflammatory event. We also explored the effects of two
      inhibitors of tumour necrosis factor (TNF) production, thalidomide and
      pentoxifylline, in neutrophil recruitment and the oedematogenic activity of these
      toxins. Subplantar injection of toxin A induced paw oedema with a maximal
      response at 1 microg, reaching a maximal value 9 hr after toxin A challenge
      (toxin A 1 microg:1.39+/-0.09 ml). Toxin B also showed a dose-dependent
      oedematogenic activity with a late peak at 24 hr and a maximal response at a dose
      of 0.1 microg (toxin B 0.1 microg:1.74+/-0.12 ml). Pentoxifylline, but not
      thalidomide, significantly reduced the oedema induced by Toxin A (pentoxifylline
      135 mg/kg:60% of inhibition) and Toxin B (pentoxifylline 135 mg/kg:33.6% of
      inhibition). Both thalidomide and pentoxifylline were able to significantly
      reduce neutrophil influx into the peritoneal cavities of rats evoked with Toxin A
      (thalidomide 45 mg/kg: 53.1% of inhibition; pentoxifylline 45 mg/kg:47.1% of
      inhibition) and Toxin B (thalidomide 45 mg/kg:46.8% of inhibition; pentoxifylline
      45 mg/kg:63.1% of inhibition). This study demonstrates the oedematogenic
      activities of both toxins with distinct potencies and time-courses. These data
      also show an inhibitory effect of pentoxifylline in toxin A and B-induced paw
      oedema. Furthermore, both pentoxifylline and thalidomide significantly inhibited
      the Clostridium difficile toxins-induced neutrophil migration.

PMID- 11453372
TI  - Na+ and K+ dependence of morphological changes of cultured rat cortical
      astrocytes.
AB  - Cultured astrocytes display flattened, polygonal morphology in the absence of
      stimuli, and change into process-bearing stellate cells in response to specific
      stimuli. In the present study, we investigated possible role of Na+, K+ and Ca2+
      in this morphological change of cultured rat cortical astrocytes. Astrocyte
      stellation induced by dibutyryl cyclic AMP (1 mM), phorbol ester (100 nM) or
      amyloid beta peptide (20 microM) was partly suppressed by replacing NaCl with
      choline chloride or LiCl in the extracellular medium or by adding KCl, and was
      completely abolished by replacing NaCl with KCl. Furthermore, the astrocyte
      stellation was blocked by the specific Na+-K+ pump inhibitor ouabain. However, it
      was not significantly affected by removing CaCl2 from the extracellular medium
      nor by adding the voltage-dependent Ca2+ channel blocker nicardipine. These
      results suggest that Na+ and K+, but not Ca2+, electrochemical gradients across
      the plasma membrane are necessary for morphological changes of astrocytes. In
      addition, amyloid beta25-35-induced stellation was most susceptible to changing
      Na+ and K+ concentrations or ouabain, while phorbol ester-induced stellation was
      least sensitive, demonstrating that the Na+ and K+ dependence differs among
      stimuli.

PMID- 11453373
TI  - The haemodynamic effects of losartan after right ventricle infarct in young pigs.
AB  - The effect of an intravenous bolus injection of the type 1 angiotensin II
      receptor antagonist, losartan on haemodynamics after right heart infarct was
      studied in an experimental setting. Right heart infarct was induced in twelve
      young swine and losartan was given in a bolus intravenous dose one hr later to
      five animals, while seven animals served as controls. Haemodynamics were then
      followed for one hr at 15 min intervals. Losartan was subsequently shown to
      decrease central venous pressure and wedge pressure, while cardiac output, left
      ventricle stroke work and stroke volume all showed improvement. Compared to the
      control animals, pulmonary vascular resistance, systemic vascular resistance and
      systemic pressures were unaffected by the drug, as was heart rate. The use of
      losartan shortly after right heart infarct reduced both right and left heart
      preload as well as inducing an improvement in cardiac performance. At the same
      time, systemic pressures and heart rate were maintained. We conclude that an
      inhibition of angiotensin II action may be a benefit in the treatment of right
      heart failure symptoms during the first hours after right heart infarct.

PMID- 11453374
TI  - A simple method for quantitative risk assessment of non-threshold carcinogens
      based on the dose descriptor T25.
AB  - This report provides guidance for using the dose-descriptor T25 from animal
      studies as a basis for quantitative risk characterisation of non-threshold
      carcinogens. T25 is presently used within the European Union for setting specific
      concentration limits for carcinogens in relation to labelling of preparations
      (formulations). The T25 is defined as the chronic dose rate which will give 25%
      of the animals tumours at a specific tissue site, after correction for
      spontaneous incidence, within the standard life-time of that species. The T25 is
      converted to the corresponding human dose descriptor, HT25, by dividing it with
      the appropriate scaling factor for interspecies dose scaling based on comparative
      metabolic rates. Subsequently, the human dose (expressed in mg per kg body-weight
      per day) is calculated from the available exposure data. The corresponding human
      life-time cancer risk is then obtained by using linear extrapolation by dividing
      the exposure dose with the coefficient (HT25/0.25). The results with this new
      method, which can easily be calculated without computer programmes, are in
      excellent agreement with results from computer-based extrapolation methods such
      as the linearised multistage model and the benchmark method using LED10, even
      though the present method only takes into consideration one single dose-response
      point. To overcome possible shortcomings of the present method, the estimated
      life-time risks are proposed to be accompanied by a commentary statement giving
      an overall evaluation of data that may have bearing on the carcinogenic risk and
      that may indicate whether the real human risk is likely to be higher or lower
      than the calculated life-time risk. By using the present guidance and a
      harmonized set of criteria and default values, the calculation of life-time
      cancer risk should be transparent and easy to comprehend.

PMID- 11453375
TI  - Polyamine and redox modulation of [3H]MK-801 binding to N-methyl-D-aspartate
      receptors in the spinal cord and cerebral cortex.
AB  - The pharmacology of N-methyl-D-aspartate (NMDA) receptors shows regional
      differences in affinity for various agonists and antagonists. We have
      investigated the modulatory mechanisms acting via the polyamine, redox and proton
      sites in the cerebral cortex and the spinal cord of adult, male rats using [3H]MK
      801 binding. The affinity for glycine-independent spermine stimulation was one
      magnitude higher in cerebrocortical than in spinal cord membranes while the
      affinity for the spermine antagonist arcaine was similar. Spermine abolished the
      inhibiting effect of low pH in both regions. Thus, the difference in the
      polyamine site between the two regions seems to be restricted to agonist binding.
      The proportion of high affinity/total ifenprodil binding was approximately 35%
      both in the spinal cord and the cerebral cortex, suggesting similar relative
      amounts of the NMDA receptor subunit 2B. The affinity of ifenprodil to the high
      affinity site was however significantly higher in the cerebral cortex. Redox
      modulatory agents had similar effects in the two regions but spermine fully
      counteracted the inhibiting effect of 0.2 mM 5,5'-dithio-bis(2-nitrobenzoic acid)
      (DTNB) in the cerebral cortex while there was only a partial effect in the spinal
      cord. These data show that the regional pharmacological heterogeneity involves
      several of the mechanisms regulating the function of the NMDA receptor. The data
      also indicate that the NMDA receptor subunit 2B is much more common in spinal
      cord than previously suggested.

PMID- 11453376
TI  - Serum cortisol response to transsphenoidal surgery for Cushing disease.
AB  - OBJECT: Transsphenoidal surgery remains the optimal treatment for Cushing
      disease, but the definitions of surgical cure and failure remain debatable. In
      this study the authors evaluated serum cortisol levels in patients before and
      after they underwent transsphenoidal surgery to elucidate the patterns of
      cortisol decrease and the optimal time and criteria for determining surgically
      induced remission. METHODS: Twenty-seven patients were evaluated throughout an 8
      month period. Serum cortisol levels were obtained before surgery and at 6-hour
      intervals postoperatively. No exogenous steroid medications were administered
      until after cortisol sampling was discontinued, following diagnosis of remission.
      Twenty-one (78%) of 27 cases were labeled initial surgically induced remissions.
      Twenty-two (81%) of 27 cases were deemed surgically induced remissions at follow
      up examination. Following surgery, initial remissions and failures demonstrated
      divergent patterns of cortisol levels. No patient whose condition was deemed an
      initial surgically induced remission has experienced definitive relapse of
      disease since discharge. One patient whose condition was initially deemed a
      surgical failure, eventually was found to exhibit surgically induced remission
      without further intervention. CONCLUSIONS: Given such findings, exogenous steroid
      medications do not appear to be required for patients until after the
      determination of remission. During the 1st postoperative day, there is a time
      period during which serum cortisol values significantly differ between the
      categories of surgically induced remissions and surgical failures. Surgically
      induced remissions were identified when postoperative values of cortisol were
      lower than preoperative midnight levels and when absolute values of cortisol were
      less than 10 microg/dl. In a small proportion of patients remission on a delayed
      basis may also be demonstrated. These data allow for a simple and rapid
      determination of postoperative remission in patients undergoing transsphenoidal
      surgery for Cushing disease.

PMID- 11453377
TI  - The lateral sellar nerve plexus and its connections in humans.
AB  - OBJECT: The aim of the present study was to elucidate the systematic topography
      of the lateral sellar (cavernous sinus [CS]) nerve plexus and its connections in
      humans. METHODS: Seven specimens of human CS and adjacent regions were dissected
      in steps and stained as whole-mount preparations by using a sensitive
      acetylcholinesterase method. Another specimen was frozen, cut on a frontal plane,
      and stained for acetylcholinesterase. The human CS contains an extensive nerve
      plexus with small ganglia. The plexus is composed of a main part, the lateral
      sellar plexus proper, which is located around the abducent nerve and medial to
      the ophthalmic nerve, and a lateral extension just underneath the outermost layer
      of the lateral CS wall, which is located lateral to the trochlear and ophthalmic
      nerves. The lateral sellar plexus is connected to the internal carotid nerve, the
      pterygopalatine ganglion, and the trigeminal ganglion. From the lateral sellar
      plexus, nerve branches run along the oculomotor, trochlear, ophthalmic, and
      abducent nerves into the orbit. In addition, the lateral sellar plexus has
      multiple connections with nerves located around the internal carotid artery. The
      presence of connections between the lateral sellar plexus and functionally
      defined neural structures suggests that the plexus receives sympathetic,
      parasympathetic, and sensory contributions. CONCLUSIONS: The plexus may
      distribute nerve subpopulations to several targets, including cerebral arteries
      and orbital structures. The presence of a mixed nerve plexus that projects to a
      variety of targets indicates that injury or disease in the CS may result in a
      variety of symptoms.

PMID- 11453378
TI  - Acute ventricular hemorrhage in adults with hydrocephalus managed by corpus
      callosotomy and fenestration of the septum pellucidum. Report of three cases.
AB  - Three patients with hypertension-induced basal ganglia or thalamic hemorrhage and
      ventricular rupture underwent corpus callosotomy and fenestration of the septum
      pellucidum. A patient with a left thalamic hemorrhage underwent surgery on an
      emergency basis and made a complete physical recovery, although she retained mild
      psychomotor deficits. Another patient with a large right basal ganglia hemorrhage
      who also underwent surgery on an emergency basis retained a spastic left
      hemiparesis without evident psychomotor deficits. The third patient with a left
      thalamic and basal ganglia hemorrhage, who was initially awake and then lapsed
      into stupor days later, underwent surgery, but did not recover consciousness.
      Hydrocephalus was reversed and effectively controlled in all three patients
      without having to perform a shunt placement procedure.

PMID- 11453379
TI  - Ventriculopleural shunt obstruction and positive-pressure ventilation. Case
      report.
AB  - The authors report an unusual case of a patient with low-pressure hydrocephalus
      and a ventriculopleural shunt, in whom routine respiratory management performed
      using positive-pressure ventilation caused shunt obstruction and coma. While the
      patient received positive-pressure ventilation with external cerebrospinal fluid
      (CSF) drainage at subatmospheric pressure, the ventricles returned to normal size
      and the coma rapidly reversed. After the authors' recognition of the effect of
      positive-pressure ventilation on intrapleural pressure and ventriculopleural
      shunt function, and the subsequent removal of positive-pressure ventilation, CSF
      flow through the shunt resumed and the patient's coma resolved.

PMID- 11453380
TI  - Obstructive hydrocephalus caused by intraventricular collapse of malacotic brain.
      Case report.
AB  - The authors present the case of a 68-year-old man who experienced acute
      obstructive hydrocephalus after having suffered an infarction in the occipital
      lobe. Histopathological and serial neuroimaging examinations revealed that
      portions of a large disintegrating occipital infarct had entered the lateral
      ventricle and obstructed the passage of cerebrospinal fluid (CSF). Ventricular
      drainage was performed for 2 weeks until the patient's hydrocephalus resolved.
      The CSF initially contained a high concentration of protein (1070 mg/dl), a high
      leukocyte count of 115 cells/mm3, and a rich fibrinous exudate. Findings in the
      present case indicate that collapse of a periventricular ischemic lesion into the
      ventricles may sometimes occur not only after cerebral hemorrhage but also after
      cerebral infarction.

PMID- 11453381
TI  - Migratory neurocysticercosis mimicking a third ventricular colloid cyst. Case
      report.
AB  - The authors report on a case of solitary neurocysticercosis located in the
      anterior third ventricle of a 21-year-old Hispanic man who presented with
      progressive headache, nausea, and mental decline. The appearance of the lesion on
      computerized tomography and magnetic resonance studies was typical of that of a
      colloid cyst. which was the presumptive preoperative diagnosis. A transcortical
      transventricular microsurgical approach was used, and inspection of the anterior
      third ventricle via the ipsilateral foramen of Monro revealed no lesion.
      Inspection of the floor of the ipsilateral lateral ventricle revealed the intact
      cyst, which had migrated since the preoperative studies had been obtained. The
      lesion was removed intact, and histopathological examination confirmed the
      diagnosis of neurocysticercosis. The authors review the radiographic findings in
      this case and further illustrate the potential for neurocysticercosis to
      masquerade as other intracranial lesions.

PMID- 11453382
TI  - Inflammatory pseudotumor of the median nerve. Case report and review of the
      literature.
AB  - The authors report the presence of an inflammatory pseudotumor of the median
      nerve in a young woman who presented with a sensorimotor deficit in the median
      nerve area. Magnetic resonance (MR) images revealed a fusiform mass in the nerve,
      and the patient underwent surgery for a suspected peripheral nerve-sheath tumor.
      Her clinical condition improved slowly and notably. Histological study revealed a
      heterogeneous lymphoid infiltration with mononuclear cells, lymphocytes (mostly T
      cells), and plasmocytoid cells. Because of the unknown significance of this
      infiltration, the patient was examined to exclude the possible diagnosis of a
      systemic tumoral process. All the studies yielded negative results and no
      systemic disease was found. Later, control MR imaging revealed no tumoral
      remains, and electromyography demonstrated progressive improvement of median
      nerve function. The follow-up period has been 8 years. The cause of the lesion is
      unknown. The differential diagnosis includes benign and malignant peripheral
      nerve-sheath tumors, lymphoma, and all tumorlike lesions of peripheral nerves.

PMID- 11453383
TI  - Delayed appearance of carbon granulomas of the scalp after use of carbon fiber
      pins for refixation of a stereotactic head frame. Case report.
AB  - The authors present a case involving the formation of several carbon granulomas
      in the scalp of a woman 7 years after she underwent craniotomy. Her operation had
      included the use of carbon fiber pins for refixation of a stereotactic head
      frame. Carbon granulomas have been noted in multiple organs following surgical or
      traumatic carbon deposition, but have not been reported in association with
      neurosurgical carbon fiber pins used for head fixation. The lesions in this case
      arose a few months after initiation of chemotherapy for the patient's brain
      tumor. The relationship of carbon and cutaneous granuloma formation to adjuvant
      therapies and treatment strategies is discussed.

PMID- 11453384
TI  - Occult rupture of a giant vertebral artery aneurysm following proximal occlusion
      and intrasaccular thrombosis. Case report.
AB  - The authors describe a unique clinicopathological phenomenon in a patient who
      presented with an unruptured giant vertebral artery aneurysm and who underwent
      endovascular proximal occlusion of the parent artery followed, several days
      later, by surgical trapping of the aneurysm after delayed subarachnoid hemorrhage
      (SAH). The intraoperative finding of a thrombus extruding from the wall of the
      aneurysm at a site remote from the origin of the SAH underscores the possibility
      that occult rupture of an aneurysmal sac can occur in patients with thrombosed
      giant aneurysms.

PMID- 11453385
TI  - Malignant transformation of a gangliocytoma/ganglioglioma into a glioblastoma
      multiforme: a molecular genetic analysis. Case report.
AB  - A gangliocytoma/ganglioglioma with no atypical or malignant features was
      subtotally resected from the right temporal lobe of a 16-year-old woman. A second
      resection was performed 8 years later to treat a locally recurrent lesion with
      increased cellularity that was diagnosed as a World Health Organization Grade II
      ganglioglioma on the basis of neuropathological examination. Molecular analysis
      of the recurrent tumor revealed a TP53 gene mutation, but no amplification of the
      epidermal growth factor receptor (EGFR) gene. Radiotherapy (60 Gy) was
      administered after the second resection. The patient returned 1 year later with a
      second focal recurrence. The specimen obtained during the third resection of
      tumor exhibited exclusively astrocytic differentiation, cellular pleomorphism
      with multinucleated cells, high mitotic activity, and endothelial proliferation.
      Therefore, the tumor was diagnosed to be a glioblastoma multiforme (GBM).
      Molecular analysis of tumor DNA from the second recurrent tumor demonstrated the
      presence of the TP53 mutation, which previously had been observed in the first
      recurrent tumor, but again no evidence of EGFR amplification. Findings
      demonstrate that the presence of TP53 mutation in progressed gangliogliomas
      should be interpreted as a progression-associated mutation rather than a
      consequence of treatment. This is the first report to indicate that the molecular
      pathways of gangliocytomas/gangliogliomas progressing to become GBMs may parallel
      those of diffuse astrocytomas progressing to become GBMs.

PMID- 11453386
TI  - Cerebrospinal fluid rhinorrhea caused by metastatic angiosarcoma. Case
      illustration.

PMID- 11453387
TI  - An intradural cervical chordoma mimicking a neurinoma. Case illustration.

PMID- 11453388
TI  - Development of the Spitz-Holter valve in Philadelphia.
AB  - The history of the treatment for hydrocephalus dates back to the Fertile Crescent
      thousands of years ago. Despite three millennia of management, significant
      advances in the surgical treatment of the disease have been infrequent. During
      the 1950s, a milestone occurred at the Children's Hospital of Philadelphia, with
      the successful development of the first working shunt valve for the treatment of
      hydrocephalus. In this historical vignette, based on recent interviews with John
      Holter, D.Sc. (Hon) and Eugene Spitz. M.D., and on a review of the available
      literature, the authors narrate the exciting story of the development of the
      Spitz-Holter valve, which took place in Philadelphia during the early 1950s.

PMID- 11453389
TI  - "The art is long and the life short": the letters of Wilder Penfield and Harvey
      Cushing.
AB  - Wilder Penfield and Harvey Cushing created legacies to neurosurgery, both in
      terms of those they trained and in their philosophical approach to the field.
      Their biographies provide only brief comments on their relationship without any
      thorough examination of their personal correspondence. In this article the
      Penfield-Cushing relationship is examined through an analysis of their
      unpublished personal letters. The Penfield-Cushing correspondence is a treasure
      for neurosurgery: it provides remarkable insight into the embryonic period of the
      discipline and into the relationship of two of the most influential figures in
      modern neurosurgery.

PMID- 11453390
TI  - Interactive magnetic resonance imaging-guided management of intracranial cystic
      lesions by using an open magnetic resonance imaging system.
AB  - OBJECT: The authors present their experience with neurosurgical procedures
      requiring real-time imaging feedback such as aspiration of a cystic structure or
      abscess cavity, decompression of hydrocephalic ventricles, management of
      arachnoid cysts, and installation of permanent or temporary drainage conduits, in
      which interactive magnetic resonance (MR) imaging guidance was used to monitor
      structural alterations associated with the procedure. METHODS: Drainage of eight
      intraparenchymal brain abscesses in seven patients, decompression of space
      occupying cystic or necrotic brain tumors in four patients, and endoscopic
      management of hydrocephalus associated with arachnoid cysts in three patients
      were performed using MR imaging-guided frameless stereotaxy in an open
      configuration 0.5-tesla superconducting MR imaging system. Intraoperative MR
      imaging guidance provided accurate information on the course of the surgical
      procedure and associated intraoperative changes in tissue position, such as the
      degree of cyst aspiration, the presence or absence of hemorrhage or induced
      swelling, and changes associated with decompression of adjacent brain parenchyma
      and the ventricular system. No clinically significant complications were
      encountered in any patient. There were no targeting errors, and procedural
      objectives were accomplished in all cases. CONCLUSIONS: Drainage of brain
      abscesses, punctures of cystic or necrotic intracranial lesions with subsequent
      aspiration, and management of hydrocephalus can be performed safely and
      accurately by monitoring the procedure using real-time MR imaging to obtain
      immediate feedback on associated dynamic tissue changes.

PMID- 11453391
TI  - Occlusive hyperemia.

PMID- 11453392
TI  - Lateral sellar nerve plexus.

PMID- 11453393
TI  - Prolactin-secreting gangliocytoma.

PMID- 11453394
TI  - Translabyrinthine-transtentorial approach.

PMID- 11453395
TI  - Combined surgical and endovascular techniques of flow alteration to treat
      fusiform and complex wide-necked intracranial aneurysms that are unsuitable for
      clipping or coil embolization.
AB  - OBJECT: Certain intracranial aneurysms, because of their fusiform or complex wide
      necked structure, giant size, or involvement with critical perforating or branch
      vessels. are unamenable to direct surgical clipping or endovascular coil
      treatment. Management of such lesions requires alternative or novel treatment
      strategies. Proximal and distal occlusion (trapping) is the most effective
      strategy. In lesions that cannot be trapped, alteration in blood flow to the
      "inflow zone," the site most vulnerable to aneurysm growth and rupture, is used.
      METHODS: From 1991 to 1999 the combined neurosurgical-neuroendovascular team at
      the Massachusetts General Hospital (MGH) managed 48 intracranial aneurysms that
      could not be clipped or occluded. Intracavernous internal carotid artery
      aneurysms were excluded from this analysis. By applying a previously described
      aneurysm rupture risk classification system (MGH Grades 0-5) based on the age of
      the patient, aneurysm size, Hunt and Hess grade, Fisher grade, and whether the
      aneurysm was a giant lesion located in the posterior circulation, the authors
      found that a significant number of patients were at moderate risk (MGH Grade 2;
      31.3% of patients) and at high risk (MGH Grades 3 or 4; 22.9%) for treatment
      related morbidity. The lesions were treated using a variety of strategies-
      surgical, endovascular, or a combination of modalities. Aneurysms that could not
      be trapped or occluded were treated using a paradigm of flow alteration, with
      flow redirected from either native collateral networks or from a surgically
      performed vascular bypass. Overall clinical outcomes were determined using the
      Glasgow Outcome Scale (GOS). A GOS score of 5 or 4 was achieved in 77.1%, a GOS
      score of 3 or 2 in 8.3%, and death (GOS 1) occurred in 14.6% of the patients.
      Procedure-related complications occurred in 27.1% of cases; the major morbidity
      rate was 6.3% and the mortality rate was 10.4%. Three patients experienced
      aneurysmal hemorrhage posttreatment; in two patients this event proved to be
      fatal. Aneurysms with MGH Grades 0, 1, 2, 3, and 4 were associated with favorable
      outcomes (GOS scores of 5 or 4) in 100%, 92.8%, 71.4%, 50%, and 0% of instances,
      respectively. CONCLUSIONS: Despite a high incidence of transient complications,
      intracranial aneurysms that cannot be clipped or occluded require alternative
      surgical and endovascular treatment strategies. In those aneurysms that cannot
      safely be trapped or occluded, one approach is the treatment strategy of flow
      alteration.

PMID- 11453396
TI  - Is stagnating flow in former feeding arteries an indication of cerebral
      hypoperfusion after resection of arteriovenous malformations?
AB  - OBJECT: The authors' goal in this study was to challenge the proposed mechanism
      of the occlusive hyperemia theory, in which it is asserted that stagnating flow
      in the former feeding arteries of cerebral arteriovenous malformations (AVMs)
      leads to parenchymal hypoperfusion or ischemia, from which postoperative edema
      and hemorrhage originate. METHODS: Cortical oxygen saturation (SaO2) was measured
      in 52 patients by using microspectrophotometry in areas adjacent to AVMs before
      and after resection. The appearance of the former feeding arteries was
      categorized as normal (Group A); moderately stagnating (Group B); and excessively
      stagnating (Group C) on postoperative angiographic fast-film series. Patients and
      SaO2 values were pooled accordingly and compared using analysis of variance and
      Duncan tests (p < 0.05). Angiographic stagnation times in former feeding arteries
      were correlated in a linear regression/correlation analysis with SaO2 data (p <
      0.05). All values are given as the mean +/- standard deviation. The average
      median postoperative SaO2 in Group C (15 patients) was significantly higher than
      in Groups B (17 patients) and A (20 patients) (Group C, 75.2 +/- 8.5; Group B,
      67.5 +/- 10.8; Group A, 67.1 +/- 12 %SaO2), as was the average postoperative
      increase in SaO2 (Group C. 25.9 +/- 14.9; Group B, 14.6 +/- 14; Group A, 11.1 +/-
      14 %SaO2). Angiographically confirmed stagnation times were also significantly
      longer in Group C than in Group B (Group C, 5.6 +/- 2.5; Group B, 1.3 +/- 0.6
      seconds). A significant correlation/regression analysis showed a clear trend
      toward higher postoperative SaO2 levels with increasing stagnation time.
      CONCLUSIONS: Stagnating flow in former feeding arteries does not cause cortical
      ischemia, but its presence on angiographic studies is usually indicative of
      hyperperfusion in the surrounding brain tissue after AVM resection. In the
      context of the pathophysiology of AVMs extrapolations made from angiographically
      visible shunt flow to blood flow in the surrounding brain tissue must be regarded
      with caution.

PMID- 11453397
TI  - Efficacy of controlled-release papaverine pellets in preventing symptomatic
      cerebral vasospasm.
AB  - OBJECT: Vasospasm as a complication of subarachnoid hemorrhage is a major concern
      in clinical practice. The systemic drugs in current use are of limited value.
      Topical, intrathecal, or intraarterial papaverine administered during surgical or
      angiographic procedures is a potent vasodilating drug; however, hypotension
      limits its systemic application. Local application of papaverine in a
      biodegradable controlled- or sustained-release matrix is proposed for vasospasm
      prophylaxis to be used in patients scheduled for aneurysm surgery. METHODS:
      Controlled-release papaverine (PapaCR) drug pellets were prepared using the
      biodegradable aliphatic polyester poly(DL-lactide-co-glycolide) as the carrier
      matrix. In vitro tests were performed to determine drug kinetics. One hundred
      seventeen patients, 73 assigned to the control group and 44 assigned to the
      PapaCR-treated group, participated in this study. Patients who were deemed to be
      at high risk for the development of vasospasm were selected to participate in the
      study. During aneurysm surgery, drug pellets were placed in cisterns over
      arterial segments. In two patients, cerebrospinal fluid was sampled every 6 hours
      for the first 5 days through a lumbar catheter that had been inserted at the
      beginning of aneurysm surgery. The incidence of clinical vasospasm and Glasgow
      Outcome Scale scores in the patients were evaluated statistically. The results of
      in vitro studies showed that effective local concentrations of papaverine could
      be maintained for more than 10 days. The first-degree drug-release profile was
      demonstrated using this design. In clinical studies no adverse effects due to the
      drug were seen. The PapaCR effectively prevented development of clinical
      vasospasm. and outcome scores were significantly better in patients in the
      treated group. CONCLUSIONS: Local application of controlled- or sustained-release
      papaverine can be safely used in preventing vasospasm.

PMID- 11453398
TI  - Outcomes in a consecutive series of 111 surgically treated plexal tumors: a
      review of the experience at the Louisiana State University Health Sciences
      Center.
AB  - OBJECT: The authors conducted a retrospective study of 107 consecutive patients
      with 111 brachial plexus tumors surgically treated at the Louisiana State
      University Health Sciences Center (LSUHSC). METHODS: During a 12-year period,
      from 1986 to 1998, 371 patients with lesions of the brachial plexus underwent
      surgery at LSUHSC. Among this group, 107 patients harbored 111 tumors of the
      brachial plexus. Neural sheath tumors were the most commonly found and included
      33 neurofibromas (20 of which were associated with von Recklinghausen disease),
      36 schwannomas, and 12 malignant neural sheath tumors. Of the non-neural sheath
      tumors, 13 were benign and 17 were malignant. Presenting symptoms included pain
      (59%), palpable mass (52%), paresthesias (30%), and paresis (29%). Anterior
      supraclavicular (82%) or posterior subscapular (18%) approaches were used to
      achieve gross-total (79%) or subtotal (21%) resection of tumor. The average
      follow-up period was 38.3 months or 3.2 years. Seventy percent of patients with
      benign neural sheath tumors became free from pain postoperatively or reported
      improvement in their preoperative pain status. Function remained intact or
      improved in 50% and remained stable postoperatively in another 20% of cases.
      Preservation of function was more likely in patients who presented intact and in
      those who had not undergone a previous attempted biopsy procedure or resection
      than in those in whom such manipulation had occurred. CONCLUSIONS: Resection of
      most plexal tumors is technically feasible and associated with acceptable
      morbidity and mortality rates.

PMID- 11453399
TI  - Sensory ganglionectomy: theory, technical aspects, and clinical experience.
AB  - OBJECT: Sensory ganglionectomy offers theoretical advantages over rhizotomy but
      remains controversial because reported success rates vary widely. The authors
      sought to add to the available data on this subject and to review technical
      aspects of the surgery. METHODS: This retrospective chart review included 19
      patients, in whom 22 operations were performed and 35 sensory ganglia were
      resected between May 1995 and May 1999. The eight women and 11 men ranged in age
      from 27 to 75 years (median age 40 years, average age 42.3 years). All patients
      had undergone extensive therapy and a mean of 2.4 previous operations (median
      three, range zero-eight operations) for their pain, all without long-term pain
      relief. Duration of symptoms varied, from 1 month (for the cancer patient) to 15
      years (mean 5.9, median 4 years). Preoperatively, all patients underwent
      diagnostic selective nerve root blocks, which temporarily relieved their targeted
      pain. The duration of follow up averaged 22 months (median 13, range 1.5 [to
      death of the cancer patient]-58 months). Before undergoing the first
      ganglionectomy, nearly all patients rated their targeted pain as 8 to 10 (average
      9.6, median 10) on an analog (0-10) pain scale. At 6 months all patients rated
      their ganglionectomy-specific pain as an average of 4.5 (median 4, range 0-8),
      and pain reduction of 50% or more was achieved in 74%. At 1 year or more the 13
      patients available for study rated their pain as an average of 4.3 (median 4.5,
      range 0-9). There were no severe complications, residual pain was never worse
      than presurgical pain, and no patient experienced significant or lasting new
      motor deficits. CONCLUSIONS: Dorsal root ganglionectomy has a useful role in the
      treatment of a variety of refractory pain states, especially those involving
      radicular pain.

PMID- 11453400
TI  - Reliability of intraoperative electrophysiological monitoring in selective
      posterior rhizotomy.
AB  - OBJECT: Selective posterior rhizotomy is a well-established treatment for
      spasticity associated with cerebral palsy. At most medical centers, responses of
      dorsal rootlets to electrical stimulation are used to determine ablation sites;
      however, there has been some controversy regarding the reliability of
      intraoperative stimulation. The authors analyzed data obtained from the McGill
      Rhizotomy Database to determine whether motor responses to dorsal root
      stimulation were reproducible. METHODS: A series of 77 patients underwent
      selective dorsal rhizotomy at a single medical center. The dorsal roots from L-2
      to S-2 were stimulated to determine the threshold amplitude. The roots were then
      stimulated at 2 to 4 times the highest threshold with a 1-second 50-Hz train. A
      second stimulation run of the entire dorsal root was performed before it was
      divided into rootlets. Rootlets were individually stimulated and sectioned
      according to the extent of abnormal electrophysiological propagation. Motor
      responses were recorded by electromyography and were also assessed by a
      physiotherapist, and grades of 0 to 4+ were assigned. The difference in grades
      between the first and second stimulation trains was determined for 752 roots.
      Statistical analysis demonstrated a clear consistency in motor responses between
      the two stimulation runs, both in the electromyographic readings and the
      physiotherapist's assessment. More than 93% of dorsal roots had either no change
      or a difference of only one grade between the two trials. Furthermore, the vast
      majority of dorsal roots assigned a grade of 4+ at the first trial maintained the
      same maximally abnormal electrophysiological response during the second
      stimulation run. CONCLUSIONS: This study indicates that currently used techniques
      are reproducible and reliable for selection of abnormal rootlets. Intraoperative
      electrophysiological stimulation can be valuable in achieving a balance between
      elimination of spasticity and preservation of underlying strength.

PMID- 11453401
TI  - Mapping of receptive language cortex in bilingual volunteers by using magnetic
      source imaging.
AB  - OBJECT: There are conflicting claims in the functional imaging literature
      concerning whether different languages are represented by distinct brain
      mechanisms in individuals who are proficient in more than one language. This
      interesting theoretical issue has practical implications when functional imaging
      methods are used for presurgical language mapping. To address this issue the
      authors compared the location and extent of receptive language cortex specific to
      English and Spanish in neurologically intact bilingual volunteers by using
      magnetic source imaging. METHODS: Areas of the cortex that were specialized for
      receptive language functions were identified separately for each language in 11
      healthy adults who were bilingual in English and Spanish. The authors performed
      exactly the same procedures used routinely for presurgical receptive language
      mapping. In each bilingual individual, the receptive language-specific map always
      encompassed the posterior portion of the superior temporal gyrus. In every case,
      however, substantial differences in the receptive language maps were also
      observed for the two languages, regardless of whether each participant's first
      language was English or Spanish. CONCLUSIONS: Although the reasons for such
      differences and their ultimate significance in identifying the cerebral
      mechanisms of language are subject to continuing investigation, their presence is
      noteworthy and has practical implications for the surgical management of patients
      with lesions in the temporal and parietal regions of the dominant hemisphere.

PMID- 11453402
TI  - Large cell/anaplastic medulloblastomas and medullomyoblastomas:
      clinicopathological and genetic features.
AB  - OBJECT: Medulloblastoma is the most common malignant central nervous system
      neoplasm found in children. A distinct variant designated large cell/anaplastic
      (LC/A) medulloblastoma is characterized by frequent dissemination of
      cerebrospinal fluid (CSF) at presentation and a more aggressive clinical course.
      The authors report on their examination of the clinicopathological and genetic
      features of seven such cases encountered at their institution. METHODS: Eighty
      cases of medulloblastomas were reviewed and seven (8.8%) of these were believed
      to fit the histological and immunohistochemical criteria for LC/A
      medulloblastoma. In three cases (43%) either desmoplastic or classic
      medulloblastoma was the underlying subtype, and in two cases (28%) the LC/A tumor
      was found within the setting of medullomyoblastoma. Fluorescence in situ
      hybridization was used in six of the seven cases to characterize the presence of
      isochromosome 17q, deletion of chromosome 22q (a deletion characteristically
      found in atypical teratoid/rhabdoid tumors), and c-myc amplification. The
      patients' clinical histories revealed CSF dissemination in all cases and lymph
      node metastasis in one case. Isochromosome 17q was found in five (83%) of six
      cases. Evidence of chromosomal gains indicated aneuploidy in three tumors (50%),
      and amplification of c-myc was found in three tumors (50%). No 22q deletions were
      encountered. CONCLUSIONS: A high percentage of LC/A medulloblastomas arise within
      a background of typical medulloblastomas or medullomyoblastomas. As is the case
      in conventional medulloblastomas, the presence of 17q is a common early
      tumorigenic event; however, in a significant percentage of specimens there is
      also evidence of aneuploidy and/or amplification of c-myc. These findings
      indicate that LC/A morphological characteristics reflect a more advanced tumor
      stage than that found in pure medulloblastomas or in typical medullomyoblastomas.

PMID- 11453403
TI  - Identification of novel regions of allelic loss in ependymomas by high-resolution
      allelotyping with 384 microsatellite markers.
AB  - OBJECT: Ependymomas are rare glial neoplasms; little is known about the molecular
      pathogenesis of this tumor entity. In a previous study the authors found multiple
      genomic imbalances in ependymomas resected in 20 adults and eight children,
      including loss of chromosomes 1p, 6, 16, 17, 19q, 20q, and 22q, as well as gain
      of chromosomes 4q, 5q, 7q, 9q, and 12q on comparative genomic hybridization. The
      aim of this study was to map in more detail the commonly affected regions in
      ependymomas. METHODS: A comprehensive allelotype analysis of 16 ependymomas was
      conducted using 384 microsatellite markers that span the 22 autosomes. Based on
      this high-resolution loss of heterozygosity analysis, multiple overlapping
      deletion regions were identified as follows: 6q25.2-27, 16p12-13.1, 16q22.3-24.1,
      17q22-24, 19q12-13.2, 20q13.2-13.3, and 22q13.1-13.3. CONCLUSIONS: These data
      confirmed previous reports that loss of chromosomes 17 and 22 were common in
      ependymomas. Moreover, the authors were able to identify loss of chromosomes 13,
      16, 19, and 20 as novel findings in ependymomas. It is believed that potential
      tumor suppressor genes that reside in these commonly deleted regions may
      contribute to the molecular tumorigenesis of ependymomas.

PMID- 11453404
TI  - Detection of simian virus 40 DNA sequence in human primary glioblastomas
      multiforme.
AB  - OBJECT: Deoxyribonucleic acid oncoviruses can induce neoplastic transformation of
      cells because their viral proteins interfere with antiproliferative cellular
      proteins. Simian virus 40 (SV40) is a DNA virus that induces the emergence of
      ependymomas, choroid plexus tumors, mesotheliomas, osteosarcomas, sarcomas, and
      various tumors when injected into newborn hamsters. Recently, approximately 60%
      of human ependymomas, choroid plexus tumors, and mesotheliomas were reported to
      contain and express SV40 DNA sequences. In this study the presence of SV40 DNA
      sequences was investigated in human brain tumors. METHODS: Three of 32
      glioblastomas mutiforme (GBMs), but none of two ependymomas and five
      medulloblastomas, were found to possess SV40 DNA sequences when examined using
      polymerase chain reaction (PCR). The DNA sequence analysis of PCR-amplified
      fragments disclosed that the samples were identical to the regulatory region of
      SV40. All three GBMs, which arose in elderly patients with wild-type p53, were
      considered to be primary (de novo) tumors. Although each of the three tumors was
      immunohistochemically negative for SV40 T antigen, in situ hybridization
      successfully demonstrated the messenger RNA for SV40 T antigen. CONCLUSIONS: The
      results of this study indicate that latent infection of SV40 in elderly people
      may be implicated in the tumorigenesis of certain primary GBMs.

PMID- 11453405
TI  - Threaded cortical bone dowels for lumbar interbody fusion: over 1-year mean
      follow up in 28 patients.
AB  - OBJECT: The authors retrospectively reviewed a series of 35 patients with
      mechanical low-back or one- to two-level discogenic pain; the patients underwent
      lumbar interbody fusion in which threaded cortical bone dowels (TCBDs) were
      placed to treat degenerative disc disease. The purpose of the study was to
      delineate fusion rates and outcome data in this series of patients. METHODS: The
      series was composed of 18 women and 17 men whose mean age was 46 years (range 17
      76 years). There were nine active cigarette smokers. All patients presented with
      symptoms consistent with mechanical low-back or discogenic pain, and magnetic
      resonance imaging revealed degenerative changes related to disc collapse at one
      or two vertebral levels. For placement of the TCBDs, 23 patients underwent
      posterior lumbar interbody fusion (PLIF), whereas 12 patients underwent anterior
      lumbar interbody fusion (ALIF). In all except one patient undergoing PLIF,
      pedicle screw and rod constructs were used without posterolateral fusion. In all
      patients undergoing ALIF except one, TCBDs were used as stand-alone devices
      without supplemental fixation. At follow up the success of fusion was determined
      by static lumbar radiography and/or computerized tomography scanning. The degree
      of lumbar lordosis at the diseased level was measured immediately postoperatively
      and compared with that documented on follow-up radiological studies. Outcomes
      were assessed using a modified Prolo Scale. Excellent and good outcomes were
      considered satisfactory, and fair or poor outcomes were considered
      unsatisfactory. In 28 patients (eight ALIF and 20 PLIF) radiological and clinical
      follow-up data were considered adequate. The mean follow-up duration was 12.3
      months. Overall satisfactory outcome was 60%; 70% satisfactory outcome was noted
      in PLIF patients and 38% in ALIF patients. Osseous fusion was present in 95% of
      the patients in the PLIF group and in 13% of those in the ALIF group.
      Complications included one L-5 nerve root injury and two postoperative wound
      infections, all in patients who underwent PLIF; in an ALIF patient lateral
      breakout of one implant occurred at 8 months postoperatively. CONCLUSIONS:
      Analysis of the mean 12.3 month follow-up data indicates that there is a
      dramatically higher fusion rate in PLIF compared with ALIF procedures when TCBDs
      are used. The authors believe that it is important to note that in all the PLIF
      procedures except one, supplemental pedicle screw/rod constructs were used,
      whereas in ALIF procedures no supplemental fixation was performed. The results
      thus suggest that TCBDs are best used in PLIF in conjunction with pedicle screw
      and rod constructs.

PMID- 11453406
TI  - Pyogenic abscess of the filum terminale. Case report.
AB  - Intradural spinal abscesses are rare. They are predominantly encountered as
      intramedullary abscesses of the spinal cord and infrequently as subdural lesions.
      To their knowledge, the authors report the first case of a chronic pyogenic
      abscess of the terminal filum in an adult woman with kyphoscoliosis who presented
      with lumbar radiculopathies. Magnetic resonance imaging revealed a partly cystic
      intradural L3-4 mass that markedly enhanced after contrast administration.
      Laboratory signs of infection were absent. Intraoperatively a lobulated lesion
      observed within the terminal filum was tightly attached to neighboring nerve
      roots by fibrosis. On opening the cyst wall pus was revealed. Histological
      examination confirmed the diagnosis of a chronic abscess. Microbiological culture
      detected Staphylococcus aureus. Antibiotic therapy resulted in an uneventful
      postoperative course, with complete resolution of symptoms and radiologically
      demonstrated disappearance of the lesion. The pathogenesis and radiological
      features of the lesion are discussed. Although extremely rare, a pyogenic abscess
      should be considered in the differential diagnosis of mass lesions of the cauda
      equina, especially in patients with preexisting spinal abnormalities. Surgical
      exposure, including drainage and biopsy sampling to rule out underlying tumor,
      combined with antibiotic treatment result in a favorable outcome.

PMID- 11453407
TI  - Transvertebral pedicle fixation in severe grade spondylolisthesis. Report of
      three cases.
AB  - The ideal treatment for spinal stabilization of Myerding Grade III-IV
      spondylolisthesis remains controversial, with a variety of techniques having been
      described. The authors report on a consecutive series of three adult patients
      with high-grade slippage who were treated with transvertebral pedicle fixation
      and standard spinal instrumentation, as both primary and revision procedures.
      There were no complications from the procedure, and a good outcome was achieved
      in all patients. The results at 4- to 8-year follow-up review are presented. This
      is a relatively simple and safe method of achieving spinal stabilization, which
      bypasses some of the problems caused by the associated anatomical distortion in
      high-grade spondylolisthesis and has good results at midterm follow up.

PMID- 11453408
TI  - Superior rectal artery injury following lumbar disc surgery. Case report.
AB  - Traumatic injury of the aorta, inferior vena cava, and iliac vessels due to
      penetration of the anterior anulus fibrosus and anterior longitudinal ligament is
      a recognized complication of lumbar disc surgery. The authors report, to the best
      of their knowledge, the first case of discectomy-related superior rectal artery
      injury treated by endovascular intervention.

PMID- 11453409
TI  - Results of degenerative spondylolisthesis treated with posterior decompression
      alone via a new surgical approach.
AB  - OBJECT: The purpose of this study was to assess radiologically demonstrated
      results and clinical outcomes in patients with degenerative spondylolisthesis who
      underwent posterior decompressive surgery via a new (unilateral) approach. This
      approach allows surgeons to perform central and bilateral decompression while
      only stripping the muscles unilaterally, thus preserving the posterior
      osteoligamentous complexes. METHODS: The authors evaluated 51 consecutive
      patients in whom surgery was performed between 1987 and 1996. The mean follow-up
      period was 4.7 years. There was no statistically significant difference between
      the pre- and postoperative measurements in percentage of vertebral slippage.
      Postoperative dynamic angulation statistically decreased compared with its
      preoperative value (p < 0.05). Improvement of an average of 67% was shown on the
      Japanese Orthopaedic Association scale, and in 78% of these patients, good to
      excellent results were demonstrated. Secondary fusion was required in only three
      patients (5.9%). CONCLUSIONS: This new surgical technique offers a potential
      alternative for the treatment of degenerative spondylolisthesis in a minimally
      invasive manner, avoiding the risk of causing or aggravating postoperative spinal
      instability.

PMID- 11453410
TI  - Cysts of the atlantoaxial joint: excellent long-term outcome after posterolateral
      surgical decompression. Report of two cases.
AB  - Articular cysts of the atlantoaxial joint are infrequently described and probably
      an underreported cause of upper cervical spinal cord compression. The authors
      report on two patients with cysts located posteriorly of the dens in whom a C-1
      and partial C-2 hemilaminectomy with subtotal resection of the cyst provided
      adequate and stable decompression 1 year postoperatively. The clinical and
      magnetic resonance imaging features and the surgical approach are discussed after
      a review of the literature.

PMID- 11453411
TI  - Spontaneous craniocervical osseous fusion resulting from cervical dystonia. Case
      report.
AB  - The authors report on a 31-year-old man with spontaneous craniocervical osseous
      fusion secondary to cervical dystonia (CD). After an 8-year history of severe CD,
      the patient developed a fixed rotation of his head to the right. Three
      dimensional computerized tomography reconstructions revealed rotation and
      fixation of the occiput and C-1 relative to C-2, which was similar to that seen
      in atlantoaxial rotatory fixation. There was abnormal ossification of the
      odontoid facet joints and ligaments. Additional ossification was observed in the
      cervical soft tissue bridging the lateral mass of C-1 and the occiput. The
      patient underwent partial myectomy of the dystonic left sternocleidomastoid
      muscle and selective posterior ramisectomy of the right posterior neck muscles;
      postoperatively he experienced relief of his neck pain. In patients with CD
      refractory to conservative treatment, the appropriate timing of surgical
      treatment is important.

PMID- 11453412
TI  - Atlantoaxial stability in ossiculum terminale. Case report.
AB  - The authors describe a patient with ossiculum terminale. Thin-section three
      dimensional computerized tomography reconstructions, magnetic resonance images,
      and radiographs of the cervical spine were obtained to evaluate the atlantoaxial
      stability and structures of the ossiculum terminale. Bone had formed between the
      ossicles and the body of the odontoid process, and good atlantoaxial stability
      was clearly demonstrated.

PMID- 11453413
TI  - A craniocervical injury-induced syringomyelia caused by central canal dilation
      secondary to acquired tonsillar herniation. Case report.
AB  - The authors report on a 19-year-old man with an acquired tonsillar herniation
      caused by a craniocervical junction injury in which serial magnetic resonance
      (MR) images demonstrated patent and isolated segments of the central canal
      participating in the dilation and then formation of a cervical syrinx. The
      patient was involved in a motor vehicle accident; he developed tonsillar
      herniation as a complication of subarachnoid and epidural hemorrhage,
      predominantly observed around the cisterna magna and upper cervical canal.
      Repeated MR images obtained over an 11-month period indicated the for mation and
      acute enlargement of the syrinx. Ten months after the accident, the patient
      presented with sensory disturbance in both upper extremities and spasticity due
      to syringomyelia. He underwent craniocervical decompressive surgery and
      doraplasty, which reduced the size of syringomyelia. The authors postulate that
      the patent central canal may play a role in determining the location of a syrinx
      remote from a focus of cerebrospinal fluid obstruction.

PMID- 11453414
TI  - Use of a craniofacial miniplate for internal fixation in a young child with
      cervical instability. Case report.
AB  - Commercially available anterior cervical internal fixation devices are designed
      for placement in adults and older children. Use of these systems in preschool
      aged children is precluded due to the small size of their cervical vertebral
      bodies (VBs). The authors describe a 2-year-old boy who suffered a C3-4 injury,
      resulting in complete ligamentous disruption. Because of the gross cervical
      instability, they elected to perform surgery via posterior and anterior
      approaches, supplemented with internal fixation, during the same operation. The
      purpose of the anterior internal fixation device is to deliver compressive forces
      onto the interbody graft and keep it in place, thus optimizing the potential for
      a successful fusion. Because of the discrepancy in size between the VBs and the
      plate and screws, however, the authors were unable to use any of the standard
      anterior cervical fixation devices. Instead, they implanted a craniofacial
      miniplate, and the patient was required to wear an external halo brace. The
      miniplate provided enough stability to allow for a solid fusion. The authors
      believe that this technique is a reasonable option in young children who require
      anterior cervical fixation.

PMID- 11453415
TI  - Cervical epidural actinomycosis. Case report.
AB  - Cervical actinomycosis causing spinal cord compression is a rare clinical entity.
      In a review of the literature, the authors found only 13 cases with actinomycosis
      related spinal neurological deficit. The authors describe the case of a 26-year
      old man who presented with neck pain and partial paresis of the upper limbs.
      Magnetic resonance imaging revealed a long cervical epidural enhancing lesion
      that extended from C-1 to T-2. The radiological findings resembled metastasis and
      other epidural infections. The patient was treated medically with penicillin and
      amoxicillin for 7 months and recovered neurologically. The authors conclude that
      although cervical epidural actinomycosis is a rare clinical entity resembling
      metastasis and other infections in this region, it should be considered so that
      this unique infection can be diagnosed in the least invasive fashion and,
      whenever possible, unnecessary surgery can be avoided.

PMID- 11453416
TI  - Hematogenous pyogenic facet joint infection of the subaxial cervical spine. A
      report of two cases and review of the literature.
AB  - Two cases of hematogenous, pyogenic, subaxial cervical facet joint infection are
      reported, and the literature is reviewed. Infection of the cervical facet joint
      is a rarely diagnosed condition; only one case has been reported in the
      literature. Lumbar facet joint infections are also rare but more commonly
      reported. Approximately one fourth of facet joint infections in the lumbar spine
      are complicated by epidural abscess formation, which can lead to a neurological
      deficit. Because of the paucity of reports on cervical facet joint infections,
      the clinical characteristics of this entity are not well known. Both patients
      presented with an acute onset of unilateral neck pain that radiated into the
      ipsilateral shoulder. Frank radicular pain was initially absent. Unilateral upper
      extremity motor weakness that was attributed to associated epidural abscess or
      granulation tissue formation was also demonstrated in both patients. Leukocyte
      count and erythrocyte sedimentation rate were elevated in both cases. Magnetic
      resonance imaging was necessary to obtain an accurate diagnosis. Staphylococcus
      aureus was identified as the offending pathogen in both cases. Decompressive
      surgery and antibiotic therapy were required to cure the condition. One patient
      recovered completely and the other sustained a permanent motor deficit.
      Hematogenous cervical facet joint infection is a rare clinical entity that has
      many characteristics in common with the more-common lumbar homolog. All three
      reported cases, however, have been complicated by epidural abscess or granulation
      tissue formation that has led to a neurological deficit. This finding suggests
      that a facet joint infection in the cervical spine may have a less benign
      clinical course than that in the lumbar spine.

PMID- 11453417
TI  - Intraspinal cervical degenerative cyst. Report of three cases.
AB  - The authors report three cases of cervical degenerative cysts causing medullary
      or radiculomedullary compression. Anatomicopathological examination confirmed the
      fibrous nature of the cyst wall and the absence of a synovial layer. One of the
      cysts was embedded in the ligamentum flavum, whereas the other two were most
      lateral and adherent to the facet joint. The physiopathogenesis of these cysts is
      discussed.

PMID- 11453418
TI  - Occipitocervical pseudomalignant osseous tumor of the soft tissue (Fasciitis
      ossificans). Case report.
AB  - The authors describe the case of a 12-year-old girl in whom a pseudomalignant
      osseous tumor of the soft tissue was diagnosed. The lesion was resected, and at 3
      year postresection follow-up examination, neuroradiological studies demonstrated
      no recurrence of the tumor.

PMID- 11453419
TI  - Anomalous vertebral artery-induced cervical cord compression causing severe nape
      pain. Case report.
AB  - The authors describe a very rare case of cervical cord compression caused by
      anomalous bilateral vertebral arteries (VAs). A 65-year-old woman had been
      suffering from intractable nape pain and torticollis. Magnetic resonance imaging
      revealed a signal void region in which spinal cord compression was present.
      Angiography demonstrated anomalous bilateral VAs compressing the spinal cord.
      Microvascular decompressive surgery was successfully performed. Neuroradiological
      and intraoperative findings are presented.

PMID- 11453420
TI  - Removal of broken pedicle screws. Technical note.
AB  - The authors describe a simple, new method for removing broken pedicle screws.
      Under microscopic visualization a straight, narrow slot is etched in the broken
      surface of the pedicle screw by using a power drill with a 2-mm diamond burr. A
      minus screwdriver is then inserted into the slot, and the broken screw is rotated
      and removed. There is no need to enlarge the screw hole around the broken screw
      or to use any special devices. The authors succeeded in removing broken screws in
      two cases, and there were no complications. This method allows preservation of
      both the pedicle and the screw hole. Consequently, it is possible to insert new
      pedicle screws into the same hole without losing the strength and stability of
      pedicle screw fixation. The authors recommend this simple and new method for
      removal of broken pedicle screws.

PMID- 11453421
TI  - Vascular injury.

PMID- 11453422
TI  - Syringomyelia.

PMID- 11453423
TI  - Intramedullary cavernoma.

PMID- 11453424
TI  - Laminectomy and kyphotic deformity.

PMID- 11453425
TI  - Odontoid fractures.

PMID- 11453426
TI  - Management of complex pediatric and adolescent spinal deformity.
AB  - OBJECT: The authors sought to analyze prospectively the outcome of surgery for
      complex spinal deformity in the pediatric and young adult populations. METHODS:
      The authors evaluate all pediatric and adolescent patients undergoing operative
      correction of complex spinal deformity from December 1997 through July 1999. No
      patient was lost to follow-up review (average 21.1 months). There were 27
      consecutive pediatric and adolescent patients (3-20 years of age) who underwent
      32 operations. Diagnoses included scoliosis (18 idiopathic, five nonidiopathic)
      and four severe kyphoscoliosis. Operative correction and arthrodesis were
      achieved via 21 posterior approaches (Cotrel-Dubousset-Horizon), seven anterior
      approaches (Isola or Kaneda Scoliosis System), and two combined approaches.
      Operative time averaged 358 minutes (range 115-620 minutes). Blood loss averaged
      807 ml (range 100-2,000 ml). Levels treated averaged 9.1 (range three-16 levels).
      There was a 54% average Cobb angle correction (range 6-82%). No case was
      complicated by the patient's neurological deterioration, loss of somatosensory
      evoked potential monitoring, cardiopulmonary disease, donor-site complication, or
      wound breakdown. There was one case of hook failure and one progression of
      deformity beyond the site of surgical instrumentation that required reoperation.
      There were 10 minor complications that did not significantly affect patient
      outcome. No patient received undirected banked blood products. There was a
      significant improvement in cosmesis, and no patient experienced continued pain
      postoperatively. All patients have been able to return to their preoperative
      activities. CONCLUSIONS: Compared with other major neurosurgical operations,
      segmental instrumentation for pediatric and adolescent spinal deformity is a safe
      procedure with minimal morbidity and there is a low risk of needing to use
      allogeneic blood products.

PMID- 11453427
TI  - Tarlov cysts: a study of 10 cases with review of the literature.
AB  - OBJECT: Tarlov or perineurial cysts are lesions of the nerve root most often
      found in the sacral region. Although there is agreement that asymptomatic Tarlov
      cysts should be followed, it is still debated whether patients with symptomatic
      Tarlov cysts should be treated surgically. The authors assessed the outcome and
      efficacy of cyst wall resection in 10 patients with symptomatic Tarlov cysts. The
      medical literature is reviewed, theories of origin are evaluated, and suggestions
      as to their cause and pathogenesis are offered. METHODS: Ten consecutive patients
      harboring symptomatic Tarlov cysts were treated by the senior author between 1989
      and 1999. All patients were assessed for neurological deficits and pain by
      neurological examination and visual analog scale, respectively. Computerized
      tomography myelography was performed in all patients to diagnose delayed filling
      of the cysts. A sacral laminectomy with resection of the sacral cyst or cysts was
      performed in all patients. Resected material from eight of 10 patients was
      submitted for histopathological evaluation. Seven (70%) of 10 patients obtained
      complete or substantial resolution of their symptoms, with an average follow up
      of 31.7 months. All of these patients had Tarlov cysts larger than 1.5 cm in
      diameter, producing radicular pain or bladder and bowel dysfunction. Three (30%)
      of 10 patients experienced no significant improvement. All three patients
      harbored Tarlov cysts smaller than 1.5 cm in diameter, producing nonradicular
      pain. Histopathological examination was performed on specimens from eight of 10
      patients, which demonstrated nerve fibers in 75% of cases, ganglion cells in 25%
      of cases, and evidence of old hemorrhage in half. CONCLUSIONS: Large cysts (> 1.5
      cm) and the presence of associated radicular symptoms strongly correlate with
      excellent outcome. Tarlov cysts may result from increased hydrostatic pressure
      and trauma.

PMID- 11453428
TI  - Clinical presentation, radiological findings, and treatment results of
      coccidioidomycosis involving the spine: report on 23 cases.
AB  - OBJECT: This study was conducted to review the presentation and management of
      patients with coccidioidomycosis involving the spine. METHODS: The authors
      reviewed 23 cases of spinal coccidioidomycosis treated at their institutions.
      There were 20 males and three females who ranged in age from 9 to 62 years. Non
      Caucasian individuals were disproportionately represented. Spinal disease was the
      first manifestation of disseminated coccidioidomycosis in 10 cases. Thirteen
      patients with meningitis, soft-tissue involvement, or pulmonary involvement
      developed new spinal lesions despite undergoing continued systemic therapy with
      amphotericin and/or fluconazole. In all patients computerized tomography and
      magnetic resonance imaging studies demonstrated preferential involvement of the
      disc spaces, vertebral bodies, and pedicles with extensive paravertebral
      phlegmons and retropharyngeal, mediastinal, or psoas abscesses. Despite the
      significant imaging findings, only four patients presented with a significant
      neurological deficit. Local pain or radiculopathy was the most common complaint.
      Twenty patients underwent invasive therapy. In five patients with prominent psoas
      abscesses and disc space disease, drainage was performed after inserting a
      percutaneous catheter. Progressive bone destruction necessitated debridement and
      fusion in one of these patients, and two others had poor outcomes after receiving
      antifungal therapy alone. Initially 15 patients underwent debridement and fusion
      in which instrumentation (10 cases) or bone graft alone was used (five cases).
      One patient worsened neurologically after surgery, and another patient required
      reoperation for a failed fusion and to correct progressive kyphosis. Four of the
      23 patients died of complications related to fungemia. Most of the 15 surviving
      patients have required long-term antifungal therapy for spinal and extraspinal
      foci. CONCLUSIONS: Spinal coccidioidomycosis can be an aggressive disease
      process. Systemic antifungal therapy fails to prevent de novo spinal involvement
      and is usually insufficient treatment for established spinal disease.

PMID- 11453429
TI  - Height of cervical foramina after anterior discectomy and implantation of a
      carbon fiber cage.
AB  - OBJECT: The authors evaluate the effects of implantation of a carbon fiber cage
      after anterior cervical discectomy (ACD) on the height of the foramen and the
      angulation between endplates of the disc space. METHODS: Thirteen consecutive
      patients who were scheduled for standard microscopic ACD and interbody fusion
      underwent thin-slice (1.5 mm) spiral computerized tomography scanning 1 day
      preoperatively, 1 day postoperatively, and 1 year postoperatively. Oblique
      sagittal reconstructions were made through both foramina; the height of each
      foramen and the angle between the endplates were measured. Because 16 cages were
      implanted, 32 foramina were investigated. Preoperatively, the mean height of the
      foramina (+/- standard deviation) was 8.1 +/- 1.5 mm (range 5.7-12 mm), and at I
      day postoperatively it was 9.7 +/- 1.4 mm (range 7.5-12.8 mm). This difference
      reached statistical significance (p < 0.0005). The mean foraminal height after 1
      year was 9.4 +/- 1.4 mm (range 6.9-12.7 mm). In terms of the preoperative value,
      the 1-year measurement still reached statistical difference (p < 0.005) but not
      with the direct postoperative mean foraminal height. Preoperatively the mean
      value of the angle between the two adjacent endplates was 1.3 +/- 2.4 degrees
      (range 0-8 degrees), and postoperatively it was 7.8 +/- 2.9 degrees (rauge 2-12
      degrees), which was statistically significant (p < 0.0005). CONCLUSIONS: The
      cervical carbon fiber cage effectively increased the height of the foramen even
      after 1 year, which contributed to decompression of the nerve root. The wedge
      shape of the device may contribute to restoration of lordosis.

PMID- 11453430
TI  - Cadaveric fibula, locking plate, and allogeneic bone matrix for anterior cervical
      fusions after cervical discectomy for radiculopathy or myelopathy.
AB  - OBJECT: The authors have previously reported that the results of using cadaveric
      fibula and locking plate (CF/LP) fusion following anterior cervical discectomy
      (ACD) for cervical spondylotic radiculopathy and myelopathy are superior to those
      obtained using autologous iliac crest (AIC) grafts in the short term. The long
      term results of using this construct are important in substantiating this
      improvement. The authors report on 246 consecutive patients (54% smokers) who
      underwent ACD with CF/LP fusion (175 with allogeneic bone matrix [ABM]) and
      compare them with 111 consecutive patients in whom AIC fusions (49% smokers) were
      performed by the same surgeons. METHODS: The study is a retrospective
      nonrandomized analysis, and chi-square statistics were used. Bone densitometric
      studies of AIC grafts and CF grafts were performed. A paired t-test was used for
      statistical analysis of the results. Disease in the group of patients undergoing
      CF/LP fusion included soft-disc herniation with radiculopathy in 14, soft-disc
      hemiation with myelopathy in seven, cervical spondylotic radiculopathy in 144,
      cervical spondylotic myelopathy in 75, AIC graft collapse pseudarthrosis in five,
      and ACD with no fusion collapse/kyphosis in one. Operations consisted of single
      level CF/LP fusion in 142 patients and multilevel CF/LP fusion in 104.
      Perioperative complications in the CF/LP group included three cases of transient
      hoarseness. There were no transfusions, infections, neurological injuries, or
      deaths. The mean hospital length of stay was 1.2 days (28% outpatient and 66% 23
      hour stay). The mean follow-up period was 60 months (range 12-94 months). Ten
      patients were lost to follow up after 1 year. Long-term complications included
      one traumatic plate fracture and one symptomatic pseudarthrosis with plate
      fracture. At 1 year and beyond, in 245 (99.6%) of 246 patients radiographically
      documented fusion with no motion at the fused level on flexion-extension films
      was demonstrated. There was no kyphosis, no symptomatic screw plate backout, and
      no CF/LP graft collapse (100% in the ABM group). In the 111 consecutive patients
      with AIC fusions, however, there was a 17% graft-related complication rate. There
      were significantly fewer graft-related complications in the CF/LP group (p <
      0.001). There was no difference in neurological outcome for any of the groups. In
      the groups undergoing single-level ACD there was a significantly greater chance
      of complete relief of neck pain CF/LP fusion compared with those undergoing AIC
      fusion (p < 0.02). There was a significantly greater chance of AIC collapse with
      the passage of time compared with CF graft (p < 0.02). Time until return to work
      was shorter for the CF/LP group by 5 to 6 weeks (p < 0.02). There was a higher
      rate of radiographically documented pseudarthrosis in the AIC group (p < 0.006).
      The mean bone densitometry for the CF/LP group was 0.7 g/cm2, significantly
      greater than that of the AIC group, which was 0.2 g/cm2 (paired t-test p <
      0.001). CONCLUSIONS: When fusion is necessary following ACD, the results of CF/LP
      fusion are significantly superior in the first 5 years after surgery compared
      with those for AIC fusions. It remains to be determined if demineralized ABM has
      a significant effect in enhancing fusion.

PMID- 11453431
TI  - Adjacent-segment morbidity after Graf ligamentoplasty compared with
      posterolateral lumbar fusion.
AB  - OBJECT: Of concern to spine surgeons are accelerated degenerative changes of
      motion segments located above and below where spinal fusion has been performed.
      Graf artificial ligament stabilization has been developed to avoid the adverse
      effect of spinal fusion. The object of this study was to assess the adjacent
      segment morbidity of Graf ligamentoplasty compared with posterolateral fusion
      (PF) in which instrumentation was used. METHODS: Data obtained in 45 patients who
      underwent L4-5 Graf ligamentoplasty (18 patients) or PF with instrumentation (27
      patients) were reviewed retrospectively. The minimum follow-up period was 5
      years. In the PF group a solid fusion rate of 92.6% was achieved. Radiographic
      evaluation included assessment of lumbar sagittal alignment, range of motion
      (ROM), and adjacent-disc degeneration. Adjacent-segment morbidity was clinically
      assessed by determining the reoperation rate. Graf ligamentoplasty maintained
      regional lordosis and flexibility (13 degrees in L4-5 lordosis; 4.4 degrees in L4
      5 ROM). Although there was no difference in preoperative adjacent-disc condition
      between the two groups, radiographic evidence of adjacent-disc deterioration was
      observed more frequently in patients in the PF group than the Graf group (25% and
      6% at L1-2; 38% and 6% at L2-3; 38% and 18% at L3-4; and 43% and 18% at L5
      sacrum, respectively). One case in the Graf group (5.6%) and five cases in the PF
      group (18.5%) required additional surgeries for adjacent-segment lesions.
      CONCLUSIONS: Graf ligamentoplasty cannot completely replace spinal fusion. In a
      well-selected group of patients, however, it was shown to maintain lumbar
      mobility and sagittal alignment, and it decreased the risk of adjacent-segment
      deterioration compared with PF with instrumentation.

PMID- 11453432
TI  - Microendoscopic posterior cervical laminoforaminotomy for unilateral
      radiculopathy: results of a new technique in 100 cases.
AB  - OBJECT: In this report the author presents surgery-related outcomes after
      application of a new technique. A posterior microendoscopic laminoforaminotomy
      was used for the surgical treatment of unilateral cervical radiculopathy
      secondary to intervertebral disc herniations and/or spondylotic foraminal
      stenosis. The results of this procedure are compared with those achieved using
      traditional laminoforaminotomy and anterior cervical discectomy with or without
      fusion. METHODS: One hundred consecutive patients who experienced unilateral
      cervical radicular syndromes, which were refractory to conservative therapy, and
      in whom imaging studies had confirmed lateral canal or foraminal compression,
      underwent surgical treatment. An endoscopy-assisted posterior laminoforaminotomy
      was performed using a microendoscopic visualization system for removal of
      herniated disc and foraminal decompression while the patient was in the sitting
      position. Excellent or good results were obtained in 97 patients. who returned to
      their preoperative employment and baseline level of physical activity. One
      patient returned to work but was unable to perform at baseline level; two
      patients returned to prior sedentary work but continued to have some activity
      related pain and paresthesias. Two patients reported experiencing intermittent
      paresthesias or numbness, but this did not limit their activities. There were two
      cases of dural punctures, one case of superficial wound infection, and no deaths.
      CONCLUSIONS: The microendoscopic posterior laminoforaminotomy is an effective
      alternative for the treatment of unilateral cervical radiculopathy secondary to
      lateral or foraminal disc herniations or spondylosis. In this group of patients,
      it is preferable because it does not require the sacrifice of a cervical motion
      segment, has a low incidence of complications, and is associated with a much
      quicker return to unrestricted full activity than that obtained with other
      techniques.

PMID- 11453433
TI  - Associated change in plantar temperature and sweating after transthoracic
      endoscopic T2-3 sympathectomy for palmar hyperhidrosis.
AB  - OBJECT: Transthoracic endoscopic T2-3 sympathectomy is currently the treatment of
      choice for palmar hyperhidrosis. Compensatory sweating of the face, trunk, thigh,
      and sole of the foot was found in more than 50% of patients who underwent this
      procedure. The authors conducted this study to investigate the associated
      intraoperative changes in plantar skin temperature and postoperative plantar
      sweating. METHODS: One hundred patients with palmar hyperhidrosis underwent
      bilateral transthoracic endoscopic T2-3 sympathectomy. There were 60 female and
      40 male patients who ranged in age from 13 to 40 years (mean age 21.6 years).
      Characteristics studied included changes in palmar and plantar skin temperature
      measured intraoperatively, as well as pre- and postoperative changes in plantar
      sweating and sympathetic skin responses (SSRs). In 59 patients (59%) elevation of
      plantar temperature was demonstrated at the end of the surgical procedure. In
      this group, plantar sweating was found to be exacerbated in three patients (5%);
      plantar sweating was improved in 52 patients (88.1%); and no change was
      demonstrated in four patients (6.8%). In the other group of patients in whom no
      temperature change occurred, increased plantar sweating was demonstrated in three
      patients (7.3%); plantar sweating was improved in 20 patients (48.8%); and no
      change was shown in 18 patients (43.9%). The difference between temperature and
      sweating change was significant (p = 0.001). Compared with the presympathectomy
      rate, the rate of absent SSR also significantly increased after sympathectomy:
      from 20 to 76% after electrical stimulation and 36 to 64% after deep inspiration
      stimulation, respectively (p < 0.05). CONCLUSIONS: In contrast to compensatory
      sweating in other parts of the body after T2-3 sympathetomy, improvement: in
      plantar sweating was shown in 72% and worsened symptoms in 6% of patients. The
      intraoperative plantar skin temperature change and perioperative SSR demonstrated
      a correlation between these changes.

PMID- 11453434
TI  - Effect of anti-rat interleukin-6 antibody after spinal cord injury in the rat:
      inducible nitric oxide synthase expression, sodium- and potassium-activated,
      magnesium-dependent adenosine-5'-triphosphatase and superoxide dismutase
      activation, and ultrastructural changes.
AB  - OBJECT: The inflammatory cells that accumulate at the damaged site after spinal
      cord injury (SCI) may secrete interleukin-6 (IL-6), a mediator known to induce
      the expression of inducible nitric oxide synthase (iNOS). Any increased
      production of NO by iNOS activity would aggravate the primary neurological damage
      in SCI. If this mechanism does occur, the direct or indirect effects of IL-6
      antagonists on iNOS activity should modulate this secondary injury. In this
      study, the authors produced spinal cord damage in rats and applied anti-rat IL-6
      antibody to neutralize IL-6 bioactivity and to reduce iNOS. They determined the
      spinal cord tissue activities of Na+-K+/Mg++ adenosine-5'-triphosphatase (ATPase)
      and superoxide dismutase, evaluated iNOS immunoreactivity, and examined
      ultrastructural findings to assess the results of this treatment. METHODS:
      Seventy rats were randomly allocated to four groups. Group I (10 rats) were
      killed to provide normal spinal cord tissue for testing. In Group II 20 rats
      underwent six-level laminectomy for the effects of total laminectomy alone to be
      determined. In Group III 20 rats underwent six-level T2-7 laminectomy and SCI was
      produced by extradural compression of the exposed cord. The same procedures were
      performed in the 20 Group IV rats, but these rats also received one (2 microg)
      intraperitoneal injection of anti-rat IL-6 antibody immediately after the injury
      and a second dose 24 hours posttrauma. Half of the rats from each of Groups II
      through IV were killed at 2 hours and the other half at 48 hours posttrauma. The
      exposed cord segments were immediately removed and processed for analysis.
      CONCLUSIONS: The results showed that neutralizing IL-6 bioactivity with anti-rat
      IL-6 antibody significantly attenuates iNOS activity and reduces secondary
      structural changes in damaged rat spinal cord tissue.

PMID- 11453435
TI  - Effect of frameless stereotaxy on the accuracy of C1-2 transarticular screw
      placement.
AB  - OBJECT: In recent studies some authors have indicated that 20% of patients have
      at least one ectatic vertebral artery (VA) that, based on previous criteria in
      which preoperative computerized tomography (CT) and standard intraoperative
      fluoroscopic techniques were used. may prevent the safe placement of C1-2
      transarticular screws. The authors conducted this study to determine whether
      frameless stereotaxy would improve the accuracy of C1-2 transarticular screw
      placement in healthy patients, particularly those whom previous criteria would
      have excluded. METHODS: The authors assessed the accuracy of frameless stereotaxy
      for C1-2 transarticular screw placement in 17 cadaveric cervical spines.
      Preoperatively obtained CT scans of the C-2 vertebra were registered on a
      stereotactic workstation. The dimensions of the C-2 pars articularis were
      measured on the workstation, and a 3.5-mm screw was stereotactically placed if
      the height and width of the pars interarticularis was greater than 4 mm. The
      specimens were evaluated with postoperative CT scanning and visual inspection.
      Screw placement was considered acceptable if the screw was contained within the C
      2 pars interarticularis, traversed the C 1-2 joint, and the screw tip was shown
      to be within the anterior cortex of the C-1 lateral mass. Transarticular screws
      were accurately placed in 16 cadaveric specimens, and only one specimen (5.9%)
      was excluded because of anomalous VA anatomy. In contrast, a total of four
      specimens (23.5%) showed significant narrowing of the C-2 pars interarticularis
      due to vascular anatomy that would have precluded atlantoaxial transarticular
      screw placement had previous nonimage-guided criteria been used. CONCLUSIONS:
      Frameless stereotaxy provides precise image guidance that improves the safety of
      C1-2 transarticular screw placement and potentially allows this procedure to be
      performed in patients previously excluded because of the inaccuracy of nonimage
      guided techniques.

PMID- 11453436
TI  - Screw placement in transoral atlantoaxial plate systems: an anatomical study.
AB  - OBJECT: The placement of an anterior atlantoaxial plate after transoral odontoid
      resection has been described by Harms. Recently, the authors of biomechanical and
      clinical studies have shown that this procedure, especially in combination with
      posterior wiring, is a good alternative to established, isolated posterior
      atlantoaxial fixation techniques. Reports on the anatomy of the atlas and axis
      primarily focus on the posterior surgical approach. Scarce research regarding the
      quantitative anatomy of the anterior aspect of C-1 and C-2 has been reported.
      This study was undertaken to measure relevant dimensions of C-1 and C-2 and their
      relation to the anterior transoral approach. The aim of the study was to
      determine "safe zones" for screw placement in anterior atlantoaxial plate
      fixation. METHOD: Fifty human dry C-1 and C-2 vertebrae were obtained for direct
      anatomical, radiographic, and computerized tomography (CT) measurements. Thirty
      two linear and four angular parameters were evaluated. All measurements were made
      using a digital caliper, ruler, or goniometer. Anatomical measurements were
      correlated with radiographic (anteroposterior, lateral, and craniocaudal) and CT
      (0.5-mm-slice thickness) measurements of the corresponding vertebrae.
      Additionally, bone mineral density (BMD) measurements of C-1 and C-2 were
      obtained in 20 patients. A safe zone for anterior screw placement in an atlas of
      bilateral trapezoid shape could be characterized. The average medial and lateral
      height of the trapezoid was 4.1 +/- 1.01 mm (range 1.4-6.7 mm) and 12.9 +/- 1.73
      mm (range 8.7-17.4 mm), respectively. The distance between the sagittal plane and
      the medial and lateral walls of the trapezoid was 10.2 +/- 1.42 mm (range 8.9
      12.8 mm) and 23.5 +/- 2.98 mm (range 21.7-30.7 mm), respectively. The average
      depth of the lateral masses was 22.3 +/- 2.04 mm (range 17.0-26.7 mm) in the
      sagittal plane. The average BMD in the safe zone of C-1 was 0.89 +/- 0.11 g/cm3
      (range 0.75-1.01 g/cm3). Bone mineral density measurements at C-2 revealed a
      spheroid zone of low density at the basis of the dens (0.68 +/- 0.09 g/cm3). In
      contrast, high zones of BMD were found near the articular surfaces (C1-2: 0.97 +/
      0.11 g/cm3; C2-3: 0.94 +/- 0.12 g/cm3). The safe zone for anterior axis screw
      placement was V-shaped, limited cranially by a zone of low bone density and
      laterally by the vertebral artery groove. Correlations between radiographic and
      anatomical measurements were generally good (r2 = 0.78-0.95), but they were
      higher between CT and anatomical measurements (r2 = 0.86-0.99). CONCLUSIONS: A
      quantitative understanding of the anterior anatomy of C-1 and C-2 is necessary
      when considering anterior atlantoaxial plate fixation after transoral odontoid
      resection. In this study the authors defined safe zones for anterior atlas and
      axis screw placement. The anterior atlantoaxial plate, as originally described by
      Harms, only partially respects these safe zones.

PMID- 11453437
TI  - Surgical anatomy of the C-2 pedicle.
AB  - OBJECT: The goal of this anatomical study was to investigate the surgical and
      radiographic anatomy of the C-2 pedicle in relation to transpedicular screw
      placement in occipitocervical stabilization and to establish anatomical
      guidelines for the placement of C-2 pedicle screws. METHODS: The C-2 pedicles in
      10 cadaveric spines were evaluated using both computerized tomography (CT)
      scanning and manual measurements. The specimens were scanned; the mediolateral
      and rostrocaudal angulations of each pedicle were measured, with the midline
      sagittal plane and the inferior endplate of the C-2 facet, respectively, as
      references, and values were recorded in 1 degrees increments by using a digital
      goniometer. The height, width, and length of the pedicles were also measured on
      the CT scans. Based on these measurements in conjunction with direct
      visualization of the C-2 pedicle through the C 1-2 interlaminar space pedicle
      screws were then placed. The distances from the screw entry point to the midline,
      C2-3 joint line, and the medial aspect of the vertebral artery were also
      measured. Repeated CT scanning was then performed to assess screw placement. The
      average pedicle height, width, and length measured 9.1 mm, 7.9 mm, and 16.6 mm,
      respectively, and the medial, inclination and rostrocaudal angulation averaged
      35.2 degrees and 38.8 degrees, respectively. The cortex of the pedicle was not
      violated in any of the 20 cadaveric specimens. CONCLUSIONS: Adequate preoperative
      imaging studies in conjunction with direct visualization of the C-2 pedicle make
      transpedicular fixation safe and effective.

PMID- 11453438
TI  - Primary polymorphous hemangioendothelioma of the spinal cord. Case report.
AB  - A case of polymorphous hemangioendothelioma of the spinal cord is described. This
      55-year-old woman presented with an 18-month history of lower-extremity
      sensorimotor deficit. A magnetic resonance image revealed an enhancing,
      intradural, extramedullary nodule at the T 1-2 level. On gross inspection, the
      lesion measured 3.5 cm and was firmly attached to spinal cord parenchyma and
      adjacent nerve roots. It was completely removed. Fourteen months after surgery
      the patient's neurological deficit had resolved. Polymorphous
      hemangioendothelioma is a rare vascular tumor of borderline malignancy. Most
      occur in lymph nodes. None has been reported to occur in the central and
      peripheral nervous system. Based on current experience, resection and close
      follow up seems the best therapeutic approach.

PMID- 11453439
TI  - Concurrent spinal dural and intradural arteriovenous fistulas. Case report.
AB  - Among spinal arteriovenous malformations (AVMs), dural arteriovenous fistulas
      (DAVFs) should be distinguished from intradural AVMs. The authors report the
      unusual and well-documented case of a 49-year-old man who suffered from a rapidly
      progressive myelopathy. Two concurrent spinal AVMs (one DAVF and one intradural
      direct AVF [Anson-Spetzler Type IV-B AVM]) were found located in the midthoracic
      region and in the conus medullaris, respectively. Both AVMs were successfully
      treated by surgery. To the authors' knowledge, the association of these two
      pathological entities has not been previously described. Clinically, if the
      patient fails to improve or deteriorates after the treatment of a spinal AVM, the
      presence of another AVM should be investigated by repeated angiography,
      especially if a complete spinal angiography study was not initially performed.

PMID- 11453440
TI  - Idiopathic "benign" intracranial hypertension: case series and review.
AB  - Idiopathic "benign" intracranial hypertension is an uncommon but important cause
      of headache that can lead to visual loss. This study was undertaken to review our
      experience in the diagnosis and management of idiopathic intracranial
      hypertension, giving special attention to treatments used. A retrospective chart
      review was conducted on 32 patients diagnosed with idiopathic intracranial
      hypertension between 1984 and 1995. Subjects included 23 females and ranged in
      age from 2 to 17.5 years. Headache was the most common symptom, followed by
      nausea and vomiting, double vision, and visual loss. Papilledema was the most
      common sign. Others were VIth cranial nerve palsy and compromised visual acuity
      at or within 3 months of presentation. Management included administration of
      acetazolamide or corticosteroids, lumboperitoneal shunt, optic nerve
      fenestration, and repeat lumbar puncture. Treatment combinations were used in 40%
      of cases. During follow-up, headache, papilledema, and decreased visual acuity
      persisted for longer than 10 months in a significant number of patients. We
      conclude that idiopathic intracranial hypertension causes significant short- and
      long-term morbidity with no proven effective treatment available. A prospective
      study is needed to establish the indications for treatment and the efficacy of
      the treatments used.

PMID- 11453441
TI  - Association between electroencephalographic findings and neurologic status in
      infants with congenital heart defects.
AB  - Neurologic status is of concern in infants with congenital heart defects
      undergoing open heart surgery. The association between perioperative
      electroencephalography (EEG) with acute neurologic status and subsequent outcome
      was examined in a cohort of 60 infants. Preoperative EEG and neurologic
      examinations were performed within 1 to 2 days prior to surgery (n = 27) and
      postoperatively (n = 47). Prior to surgery, 15 of 27 infants had normal EEG,
      whereas 5 had epileptiform activity and 9 had disturbances in background activity
      that were primarily moderate (8/9) and diffuse (7/9). Postoperatively, only 17 of
      47 infants had normal recordings. Newborns (<1 month) were more likely (P< .001)
      to demonstrate EEG abnormalities than infants. Epileptiform activity was
      documented in 15, whereas 28 had background abnormalities that were moderate
      severe (22/28) and diffuse (20/28) in most. Epileptiform activity prior to
      surgery was always associated with an abnormal neurologic examination, and this
      association persisted postoperatively (86%). Moderate to severe background
      abnormalities in the postoperative EEG was also strongly associated with acute
      neurologic abnormalities (93%). Severe background abnormalities (n = 5) were 100%
      predictive of death or severe disability. Long-term follow-up revealed that all
      children with normal postoperative EEGs had positive neurologic outcomes (P =
      .04); however, there were many false positives. Perioperative EEG abnormalities
      increased the likelihood for acute neurologic findings, whereas normal recordings
      following surgery were reassuring with regard to a favorable outcome.

PMID- 11453442
TI  - Childhood Guillain-Barre syndrome: clinical and electrophysiologic features
      predictive of outcome.
AB  - The hospital records of 27 children with the diagnosis of Guillain-Barre syndrome
      were retrospectively reviewed. Based on the time to recovery, patients were
      divided into two groups: group 1 consisted of children whose times to complete or
      partial recovery extended beyond 2 months from onset of the disease; group 2
      consisted of children who attained a full recovery within 2 months from onset of
      the disease. The clinical and electrophysiologic features of the two groups were
      statistically compared for their predictive value of outcome. Three clinical
      features (maximum disability score at presentation, intubation, and cranial nerve
      involvement) were predictive of poor outcome, whereas one electrophysiologic
      feature (conduction block) was predictive of favorable outcome. There was also a
      significant correlation between maximum disability score at presentation and the
      probability of intubation.

PMID- 11453443
TI  - Utility of electroencephalography in the pediatric emergency department.
AB  - To assess the role of electroencephalography (EEG) in the pediatric emergency
      department, we reviewed the records of all patients having an EEG in the
      pediatric emergency department of our hospital between 1995 and 1997. EEG
      findings, clinical presentations, and follow-up data were analyzed, and patients
      were distributed into three groups according to clinical presentation: group 1
      included patients with new-onset seizures, group 2 included patients with known
      epilepsy presenting with worsening seizures and altered mentation, and group 3
      comprised patients with acute confusional states. Overall, 56 patients with 57
      EEGs were included. In group 1 (n = 36), 20 (55.6%) had an abnormal EEG. The risk
      of recurrence was much higher in children with abnormal EEGs (80% vs. 31%) (P <
      .01). In retrospect, among all of the patients receiving the diagnosis of
      epilepsy, 76% had an abnormal emergency department EEG. Four in group 2 (n = 14)
      and one in group 3 (n = 7) were proven to have nonconvulsive status epilepticus
      and were treated accordingly. No patients in group 1 had nonconvulsive status
      epilepticus. Ongoing seizures were promptly excluded in the remainder. The EEG
      directly contributed to the diagnosis in 84% of all referrals in the pediatric
      emergency department, either being abnormal and leading to a diagnosis of a
      seizure disorder or confirming low suspicion for seizures. Thus, a prompt EEG
      should be considered in children with new-onset seizures and unexplained altered
      consciousness.

PMID- 11453444
TI  - Prospective study of recovery following neonatal brachial plexus injury.
AB  - The prognosis for recovery from brachial plexus injury sustained at or before
      birth is generally favorable. However, roughly 10% of these infants remain
      profoundly weak and later exhibit functional disability in the affected arm.
      Early identification of these at-risk infants would be helpful in selecting
      patients for surgical management. In our prospective study, 80 infants with
      brachial plexus injury were examined on a monthly basis. Complete recovery
      occurred in 53 (66%); in 9 (11%), mild weakness persisted. In each child,
      recovery to antigravity strength in the biceps, triceps, and deltoid was noted by
      6 months of age. Moderate arm weakness persisted in 7 children (9%); none had
      antigravity strength in the deltoid at age 6 months. Eleven children (14%) had
      severe permanent weakness (mean follow-up: 4.4 years). At age 6 months, these
      individuals exhibited at best 2/5 strength proximally and typically 0-1/5
      strength in the wrist and finger extensors. Our results demonstrate that detailed
      strength testing up to 6 months of age predicts not only complete recovery of
      neonatal brachial plexus injury but also those children destined for long-term
      severe disability.

PMID- 11453445
TI  - One-year outcome of auditory-tactile-visual-vestibular intervention in the
      neonatal intensive care unit: effects of severe prematurity and central nervous
      system injury.
AB  - Thirty-seven infants with severe central nervous system injury or extreme
      prematurity were randomly assigned to a multisensory (auditory-tactile-visual
      vestibular) intervention or control group. Intervention began in the hospital at
      33 weeks' postconceptional age and continued twice daily in the home until 2
      months' corrected age. Mother-infant interactions during feedings were
      videotaped, and the Bayley Scales of Infant Development were administered.
      Control mothers stimulated their infants more during feeding, but these
      significant differences dissipated by 4 months. The presence of periventricular
      leukomalacia was associated with significantly poorer mental development,
      regardless of group assignment. Experimental infants tended to exhibit better
      motor and mental performance and had 23% fewer cerebral palsy diagnoses at 1
      year, but these trends were not statistically significant. The type of brain
      injury was more important in determining 1-year developmental outcome than type
      of postnatal experience, suggesting that periventricular leukomalacia presents a
      major challenge for infant development.

PMID- 11453446
TI  - Neuropsychiatric genetics: misclassification in linkage studies of phenotype
      genotype research.
AB  - Research on neuropsychiatric disorders has produced a number of very important
      findings in the last few decades. However, several problems continue to hinder
      research in this area. One problem area has been the appropriate classification
      of disease status for probands and extended family members in linkage studies. In
      this article, we examine rates of misclassification in a 12-year follow-up study
      of children previously diagnosed with Tourette syndrome. At the 12-year follow
      up, we found a 5 to 12% rate of misclassification of previously diagnosed cases.
      We present a model of a linkage study with three classification steps. The model
      demonstrates that an error rate of 5% would result in misclassification of 20% of
      true cases by step three. Adding additional steps to improve diagnostic accuracy
      may increase rather than decrease classification error.

PMID- 11453447
TI  - Pseudomeningoencephalitic presentation of pediatric Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome is an acute, autoimmune polyradiculoneuropathy that
      improves with immune-modulating treatment if instituted early in the illness.
      Preliminary diagnosis relies on the clinician's recognition of the typical
      symptoms and signs as supporting evidence of the illness, such as nerve
      conduction studies, which may not be available emergently. We report eight
      children with Guillain-Barre syndrome in whom the initial presentation was
      atypical and suggested a primary central nervous system illness. In these
      patients, the predominant clinical symptoms included drowsiness, headache,
      irritability, and meningismus, although the classic features of Guillain-Barre
      syndrome (weakness, hyporeflexia) were also present. The atypical presentation
      caused delay in diagnosis in some cases. It is important to recognize this
      variant of pediatric Guillain-Barre syndrome to ensure expeditious diagnosis and
      treatment.

PMID- 11453448
TI  - Etiologic yield of autistic spectrum disorders: a prospective study.
AB  - At present, the etiologic yield in community-derived samples of young children
      with an autistic spectrum disorder is not known. To address this question, all
      young children (under 5 years of age) referred for an initial assessment to
      ambulatory pediatric neurology or developmental pediatric clinics at a tertiary
      university center over an 18-month period for a suspected developmental delay
      were prospectively identified. Specific diagnostic testing was left to the
      discretion of the evaluating physician. In all, 50 children with an autistic
      spectrum disorder were assessed. Detailed history or physical examination was
      informative with respect to suggesting the possibility of an underlying etiology
      in a minority (10/50,20%). Genetic studies (FMR-1, karyotype),
      electroencephalography (EEG), and neuroimaging were carried out in a majority
      (42/50, 34/50, and 33/50, respectively) of the children, for the most part on a
      screening rather than an indicated basis (31/42, 34/34, and 28/33, respectively).
      Etiologic yield was low (1/50, 2%), with only a single child identified with a
      possible Landau-Kleffner variant on sleep EEG tracing. The results suggest an
      evaluation paradigm with reference to etiologic determination for young children
      with autistic spectrum disorder that does not presently justify metabolic or
      neuroimaging on a screening basis. Recurrence risk and treatment implications,
      however, suggest that strong consideration be given to genetic (FMR-1, karyotype)
      testing and EEG study despite a relatively low yield.

PMID- 11453449
TI  - Political strategy 101: how to make health policy and influence political people.
AB  - Many health policy decisions that affect how health care professionals care for
      their patients are made by the federal government or state and local governments.
      For most health care professionals, the policy-making process is a mystery.
      Health policy decisions made by elected and appointed officials in various
      branches of government are influenced by political factors often unfamiliar to
      the decision-making process of health care professionals. With some guidance on
      how to think critically about politics, health care professionals can influence
      the development, passage, and implementation of government-sponsored health
      policies that affect their patients. Based on insights gleaned from experience,
      accounts of the policy-making process, and political science literature, this
      article describes a process of gathering and analyzing political information that
      can aid physicians in developing a strategy that will help them influence the
      political agenda and their patients' care.

PMID- 11453450
TI  - Warren A. Weinberg, M.D. Chair in Pediatric Neurology and Learning.

PMID- 11453451
TI  - Magnetic resonance spectroscopy and magnetic resonance imaging findings in
      Krabbe's disease.
AB  - Two twins with late infantile globoid cell leukodystrophy of Krabbe's disease
      were studied with conventional magnetic resonance imaging (MRI) and proton
      magnetic resonance spectroscopy. Brain MRI demonstrated brain atrophy with
      extensive bilateral symmetric abnormal T2 signal in the posterior periventricular
      white matter, parietal lobes, corona radiata, centrum semiovale, and splenium of
      the corpus callosum. Magnetic resonance imaging-guided proton magnetic resonance
      spectroscopy revealed prominent peaks from choline-containing compounds, total
      creatine, and inositols. The N-acetylaspartate peak was markedly reduced, and the
      choline-to-N-acetylaspartate ratio was abnormally high; in one of the twins,
      lactic acid was also detected. The constellation of magnetic resonance
      spectroscopy findings is indicative of extensive demyelination, gliosis, and loss
      of axons in the involved white matter; the latter two events occur in the later
      stages of globoid cell leukodystrophy. In conjunction with brain MRI, these
      magnetic resonance spectroscopy findings may alert clinicians to the possibility
      of leukodystrophy in children with progressive encephalopathy.

PMID- 11453452
TI  - Diffusion-weighted imaging in moyamoya disease.
AB  - Moyamoya disease is characterized by progressive intracranial vascular stenoses
      of the circle of Willis, resulting in successive ischemic events. We report
      serial diffusion-weighted imaging studies in a case of moyamoya disease. A 4-year
      old right-handed patient presented with multiple infarcts in the right and left
      hemispheres. Each new infarct was unambiguously recognized as bright on diffusion
      weighted imaging. Previous infarcts, readily detected on other magnetic resonance
      imaging sequences, were not bright on diffusion-weighted imaging. The patient
      subsequently underwent bilateral synangiosis. In this case, the diffusion
      weighted images were helpful in assessing the extent of infarcts, determining the
      age of the lesion, and correlation with new clinical findings. We emphasize the
      usefulness of diffusion-weighted imaging for following the clinical course of
      children with moyamoya disease, in whom new focal deficits are highly suspicious
      of new infarcts.

PMID- 11453453
TI  - A5814G mutation in mitochondrial DNA can cause mitochondrial myopathy and
      cardiomyopathy.
AB  - We describe a 5-year-old child with hypertrophic cardiomyopathy, mitochondrial
      myopathy, and lactic acidosis. Mitochondrial DNA analysis showed a heteroplasmic
      A5814G point mutation in the tRNA(Cys) gene. The mutational load was extremely
      high (>95%) in muscle, fibroblasts, and blood. This report expands the clinical
      heterogeneity of the A5814G mutation, which should be considered in the
      differential diagnosis of hypertrophic cardiomyopathy in childhood.

PMID- 11453454
TI  - High mitochondrial DNA T8993G mutation (<90%) without typical features of Leigh's
      and NARP syndromes.
AB  - Neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome and maternally
      inherited Leigh's syndrome have been associated with T8993G point mutations in
      the mitochondrial adenosine triphosphatase 6 gene. Typically, NARP syndrome is
      characterized by developmental delay, seizures, dementia, retinitis pigmentosa,
      ataxia, sensory neuropathy, and proximal weakness. Usually, there is a
      correlation between the percentage of mutated mitochondrial DNA and clinical
      severity, and when mutated mitochondrial DNA is > 90%, it is often seen with
      Leigh's syndrome. We now report a family with mitochondrial DNA T8993G mutation
      in eight living members, five with mutant mitochondrial DNA >90% and one with 20%
      mutant mitochondrial DNA. However, their clinical features include variable
      combinations of seizures, behavior problems, learning disability, mental
      retardation, sensorineural deafness, cerebellar ataxia, and proximal muscle
      weakness. No retinitis pigmentosa was found in all eight living members,
      including a 56-year-old grandmother. Only one dead female relative was diagnosed
      with Leigh's syndrome on the neuropathologic examination at age 22 years, when
      she died of an accident. High mitochondrial DNA T8993G mutation is not always
      associated with typical features of Leigh's and NARP syndromes.

PMID- 11453455
TI  - Delayed diagnosis of pediatric Langerhans' cell histiocytosis: case report and
      retrospective review of pediatric cases seen at Mayo Clinic.
AB  - Langerhans' cell histiocytosis is a disease of the dendritic histiocytes with a
      wide variety of clinical manifestations. This report describes a boy with
      Langerhans' cell histiocytosis who presented with primarily neurologic and
      endocrinologic findings, without pain. The diagnosis of Langerhans' cell
      histiocytosis was not made until 10 years after symptom onset. The pathology
      database at Mayo Clinic was searched for cases of Langerhans' cell histiocytosis
      between 1985 and 1999 under 19 years of age (65 children), and information
      regarding clinical presentation was abstracted. Database review found a range of
      1 day to 156 weeks (mean 13.8 weeks) from symptom onset to diagnosis. No other
      patients with primarily neurologic symptoms were found. The diagnosis of
      Langerhans' cell histiocytosis was made significantly sooner after onset if pain
      was present (chi-square = 19.1, P < .001, two-tailed, phi coefficient 0.54). Our
      findings indicate that neurologic manifestations of Langerhans' cell
      histiocytosis are rare, and the combination of diabetes insipidus, ataxia, skin
      rash, or osseous pain should alert the clinician to the possibility of
      Langerhans' cell histiocytosis and avoid delayed diagnosis.

PMID- 11453456
TI  - Acute encephalopathy associated with nontyphoidal salmonellosis.
AB  - The importance of an acute encephalopathy associated with nontyphoidal
      salmonellosis has recently been recognized, but the disease entity has been
      poorly established. In this study, we describe two encephalopathic patients
      associated with nontyphoidal salmonellosis. The patients exhibited a rapid
      evolution of coma after the onset of lethargy or seizure. Fever and diarrhea due
      to salmonellosis preceded these events. Secondary factors inducing
      encephalopathies, such as severe dehydration, sepsis, meningitis, electrolyte or
      metabolic disturbances, acute renal failure, and multiple organ failure, were
      excluded in the differential diagnosis at the onset of encephalopathic features.
      These clinical findings and rapid development of encephalopathic features from
      localized intestinal infection without any significant abnormalities in a variety
      of blood tests may suggest a toxic etiology. However, endotoxin was not found in
      serum from both patients. From these results, we conclude that nontyphoidal
      salmonellosis can cause a toxic encephalopathy syndrome, like shigellosis or
      verocytotoxin-producing Escherichia coli infection.

PMID- 11453457
TI  - Enzymatic synthesis of oligosaccharides by two glycosyl hydrolases of Sulfolobus
      solfataricus.
AB  - The importance of carbohydrates in a variety of biological functions is the
      reason that interest has recently increased in these compounds as possible
      components of therapeutic agents. Thus, the need for a technique allowing the
      easy synthesis of carbohydrates and glucoconjugates is an emerging challenge for
      chemists and biologists involved in this field. At present, enzymatic synthesis
      has resulted in the most promising approach for the production of complex
      oligosaccharides. In this respect, the enzymological characteristics of the
      catalysts, in term of regioselectivity, substrate specificity, and operational
      stability, are of fundamental importance to improve the yields of the process and
      to widen the repertoire of the available products. Here, two methods of
      oligosaccharide synthesis performed by a glycosynthase and by an alpha-xylosidase
      from the hyperthermophilic archaeon Sulfolobus solfataricus are briefly reviewed.
      The approaches used and the biodiversity of the catalysts together are key
      features for their possible utilization in the synthesis of oligosaccharides.

PMID- 11453458
TI  - Thermoadaptation of a mesophilic hygromycin B phosphotransferase by directed
      evolution in hyperthermophilic Archaea: selection of a stable genetic marker for
      DNA transfer into Sulfolobus solfataricus.
AB  - A mutated version of the hygromycin B phosphotransferase (hph(mut)) gene from
      Escherichia coli, isolated by directed evolution at 75 degrees C in transformants
      of a thermophilic strain of Sulfolobus solfataricus, was characterized with
      respect to its genetic stability in both the original mesophilic and the new
      thermophilic hosts. This gene was demonstrated to be able to express the
      hygromycin B resistance phenotype and to be steadily maintained and propagated
      also in other, more thermophilic strains of S. solfataricus, i.e., up to 82
      degrees C. Furthermore, it may be transferred to S. solfataricus cells by
      cotransformation with pKMSD48, another extrachromosomal element derived from the
      virus SSV1 of Sulfolobus shibatae, without any loss of stability and without
      affecting the replication and infectivity of this viral DNA. The hph(mut) and the
      wild-type gene products were expressed at higher levels in E. coli and purified
      by specific affinity chromatography on immobilized hygromycin B. Comparative
      characterization revealed that the mutant enzyme had acquired significant
      thermoresistance and displayed higher thermal activity with augmented catalytic
      efficiency.

PMID- 11453459
TI  - Molecular cloning and characterization of thermostable DNA ligase from Aquifex
      pyrophilus, a hyperthermophilic bacterium.
AB  - A DNA ligase gene from the hyperthermophilic bacterium Aquifex pyrophilus (Ap)
      was cloned and sequenced. An open reading frame of 2,157 bp that codes for a 82
      kDa protein showed 40%-60% homology with a series of NAD+-dependent DNA ligases
      from different organisms. The recombinant enzyme Ap DNA ligase expressed in
      Escherichia coli was purified to homogeneity and characterized. The activity of
      Ap DNA ligase gradually increased in proportion to the concentration of
      monovalent salt up to 200 mM NaCl, 150 mM KCl, 200 mM NH4Cl, and 350 mM potassium
      glutamate. The optimum temperature and pH of Ap DNA ligase were greater than 65
      degrees C and 8.0-8.6, respectively, for nick-closing activity. More than 75% of
      the ligation activity was retained after incubation at 95 degrees C for 60 min,
      whereas the half-lives of Thermus aquaticus and Escherichia coli DNA ligases at
      95 degrees C were < or =15 min and 5 min, respectively. Thermostable Ap DNA
      ligase was applied to repeat expansion detection (RED) and could be a useful
      enzyme in DNA diagnostics.

PMID- 11453460
TI  - Isolation of the fibrocrystalline body, a structure present in haloarchaeal
      species, from Halobacterium salinarum.
AB  - An organized structure, the fibrocrystalline body (FB), has been isolated from
      the archaeon Halobacterium salinarum. The structure is also present in, and can
      be isolated from, other extreme halophilic archaea. FB is present in the
      cytoplasm during the exponential growth and early stationary phases. This
      structure is affected by vincristine, an antitumoral drug, which targets tubulin.
      The drug causes fragmentation of the FB, changes in the cell shape, and growth
      inhibition. Taken together, these results point toward an important role in the
      life of the cell for this highly organized structure.

PMID- 11453461
TI  - Interaction of TIP26 from a hyperthermophilic archaeon with TFB/TBP/DNA ternary
      complex.
AB  - Interactions of TBP-interacting protein (TIP26), TBP, and TFB from a
      hyperthermophilic archaeon Thermococcus kodakaraensis KOD1 with TATA-DNA were
      examined by electrophoretic mobility shift assay. Tk-TFB formed a ternary complex
      with Tk-TBP and TATA-DNA. Tk-TIP26 did not inhibit the formation of this ternary
      complex, but interacted with it to form a TIP26/TFB/TBP/DNA quaternary complex.
      This interaction is rather weak, and a large excess of Tk-TIP26 over Tk-TBP is
      required to fully convert the TFB/TBP/DNA ternary complex to the quaternary
      complex. However, determination of the concentration of Tk-TIP26 and Tk-TBP in
      KOD1 cells by Western blotting analysis indicated that the concentration of Tk
      TIP26 is approximately ten times that of Tk-TBP, suggesting that the quaternary
      complex might also form in vivo.

PMID- 11453462
TI  - Molecular and biochemical characterization of the recombinant amidase from
      hyperthermophilic archaeon Sulfolobus solfataricus.
AB  - We have cloned, sequenced, and overexpressed in Escherichia coli the amidase gene
      from the hyperthermophilic archaeon Sulfolobus solfataricus (strain MT4). The
      recombinant thermophilic protein was expressed as a fusion protein with an N
      terminus six-histidine-residue affinity tag. The enzyme, the first characterized
      archaeal amidase, is a monomer of 55,784 daltons, enantioselective, and active on
      2- to 6-carbon aliphatic amides and on many aromatic amides, over the pH range 4
      9 and at temperatures from 60 degrees to 95 degrees C. The S. solfataricus
      amidase belongs to the class of amidases that share a characteristic signature,
      GGSS(S/ G)GS, located in the central region of the protein, and which show
      remarkable variability in their individual substrate specificities, can hydrolyze
      aliphatic or aromatic substrates, and share a large invariance of their primary
      structure.

PMID- 11453463
TI  - Innovative fermentation strategies for the production of extremophilic enzymes.
AB  - A new type of microfiltration (MF) bioreactor, developed in our laboratory, was
      investigated for use in improving efficiency of the production of extremophilic
      enzymes. In spite of the difficulties in cultivating hyperthermophiles, we
      achieved, in 300 h fermentation, more than 38 g/l dry weight of Sulfolobus
      solfataricus using a MF technique, and we demonstrated that the activity of
      alcohol dehydrogenase (ADH), as the reporter enzyme, was not affected by cell
      density. However, hyperthermophile cultivation is difficult to scale up because
      of evaporation and the very low growth rate. Thus, to achieve high productivity
      we cultivated, in the MF bioreactor, recombinant mesophilic hosts engineered for
      the production of two thermophilic enzymes, namely, trehalosyldextrin-forming
      enzyme (SsTDFE) and trehalose-forming enzyme (SsTFE) from Sulfolobus
      solfataricus. The traditional Luria-Bertani broth used for recombinant
      Escherichia coli growth was replaced with a semidefined medium. The latter was
      used in both the batch and the MF experiments, and the ratio of complex
      components (e.g., yeast extract and tryptone) to a simple carbon source
      (glycerol) was decreased during the fed-batch phase to further decrease the
      medium cost in view of industrial applications. The bioprocess developed was able
      to improve productivity 500 fold for rSsTFE and 60 fold for rSsTDFE with respect
      to the wild type cultivated in MF mode. Comparisons with another recombinant
      enzyme, alpha-glucosidase (rSsalphagly), from Sulfolobus solfataricus produced in
      our MF bioreactor are reported.

PMID- 11453464
TI  - Characterization of alanine and malate dehydrogenases from a marine psychrophile
      strain PA-43.
AB  - Alanine dehydrogenase (AlaDH: EC 1.4.1.1), malate dehydrogenase (MDH: EC
      1.1.1.37), and glutamate dehydrogenase (EC 1.4.1.2), all NAD+ dependent, were
      detected in extracts from a psychrophilic bacterium, strain PA-43, isolated from
      a sea urchin off the Icelandic coast. Characterization tests suggested that the
      strain had a close relationship to Vibrio, but sequencing of part of the 16S rDNA
      gene placed the bacterium among Shewanella species in a constructed phylogenetic
      tree. The bacterium had an optimum growth temperature of 16.5 degrees C, and
      maximum dehydrogenase expression was obtained in a rich medium supplemented with
      NaCl. Both AlaDH and MDH were purified to homogeneity. AlaDH is a hexamer, with
      an approximate relative molecular mass of 260,000, whereas MDH is dimeric, with
      an apparent relative molecular mass of approximately 70,000. Both enzymes were
      thermolabile, and the optimum temperatures for activity were shifted toward lower
      temperatures than those found in the same enzymes from mesophiles, 37 degrees C
      for MDH and approximately 47 degrees C for AlaDH. The pH optima for AlaDH in the
      forward and reverse reactions were 10.5 and 9, respectively, whereas those for
      MDH were 10-10.2 and 8.8, respectively. Partial amino acid sequences, comprising
      approximately 30% of the total sequences from each enzyme, were determined for N
      terminal, tryptic, and chymotryptic fragments of the enzymes. The AlaDH showed
      the highest similarity to AlaDHs from the psychrotroph Shewanella Ac10 and the
      mesophile Vibrio proteolyticus, whereas MDH was most similar to the MDHs from the
      mesophiles Escherichia coli and Haemophilus influenzae, with lower identity to
      the psychrophilic malate dehydrogenases from Vibrio 5710 and Photobacterium SS9.

PMID- 11453465
TI  - The use of multistate life-table models for improving population health.
AB  - We demonstrate how incidence, prevalence, remission, mortality (IPRM) models may
      be constructed on population life-tables, how the incidence of a condition may be
      calculated, and how the consequences of demographic changes and public health
      interventions may be predicted. We illustrate the methodology by applying it to
      the epidemiology of diabetes, physical inactivity and obesity in New Zealand.

PMID- 11453466
TI  - Tumour dynamics and necrosis: surface tension and stability.
AB  - A model is developed for the motion of cells within a multicell spherical tumour.
      The model allows either for the intercellular forces to be in compression and
      cells to be compacted to a fixed number density, or for the cell number density
      to fall and cells to become isolated from each other. The model develops necrotic
      regions naturally due to force balances rather than being directly attributable
      to a critical oxygen concentration. These necrotic regions may result in a
      gradual reduction in local cell density rather than jump to a completely dead
      region. Numerical and analytical analysis of the spherically symmetric model
      shows that the long time behaviour of the spheroid depends on any surface tension
      effects created by cells on the outer surface. For small surface tension the
      spheroid grows linearly in time developing a large necrotic region, while for
      larger surface tension the growth can be halted. The linear stability to
      spherically symmetric perturbations of all the possible resulting steady states
      is revealed.

PMID- 11453467
TI  - Pro-inflammatory--anti-inflammatory cytokine dynamics mediated by cytokine
      receptor dynamics in monocytes.
AB  - Many of the major human diseases, both infectious (septic shock syndromes) and
      idiopathic (for example, rheumatoid arthritis), are driven by the production of
      the pro-inflammatory cytokines interleukin-1 (IL-1) and tumour necrosis factor
      alpha (TNF-alpha) produced by monocytes and macrophages. These key pro
      inflammatory cytokines can, in turn, stimulate the production of additional
      cytokines which, in totality, generate tissue pathology. A major deactivator of
      activated, cytokine-producing monocytes and macrophages is the anti-inflammatory
      cytokine interleukin-10 (IL-10). It is known that the interactions between these
      three cytokines are pivotal in terms of health and pathology, but almost nothing
      is known of the dynamics of these interactions. In this study we have modelled
      the autocrine interactions of TNF-alpha, IL-1 and IL-10 with monocytes. The model
      constructed is a six-dimensional, continuous-time dynamical system, with free IL
      1 and IL- 10 concentrations in the cell's vicinity, and the proportions of bound
      and free IL-1 and IL-10 cell-surface receptors, which transduce the cell's
      response to stimulation, as the state variables. The monocyte is assumed to be
      initially in a quiescent state, and it is stimulated to produce IL-1 by an
      external stimulus (e.g. exposure to TNF-alpha or lipopolysaccharide, LPS). This
      in turn invokes an autocrine IL-1 response, and also induces the production of
      the anti-inflammatory cytokine IL-10, which acts to downregulate IL-1 production.
      These responses are mediated by specific cell-surface receptors, the
      concentrations of which may also be subject to stimulated upregulation. We
      analyse a reduced, four-dimensional version of the model, and explore its
      asymptotic states. We find a variety of possible outcomes: runaway IL-1
      production, multiple stable equilibria, stable limit cycles, and, exceptionally,
      quasi-periodic behaviour. These behaviours depend crucially on the form of the
      cell's response functions. The possible biological implications of these
      phenomena are discussed.

PMID- 11453468
TI  - Variable maturation velocity and parameter sensitivity in a model of
      haematopoiesis.
AB  - We analyse an age-structured model for haematopoiesis, describing the development
      of specialized cells in the blood from undifferentiated stem cells and including
      the controlling effects of hormones. Variation in the length of time for maturing
      of precursor cells in this model has a stabilizing influence. When the maturing
      process does not vary, then the age-structured model reduces to a delay
      differential equation. Depending on the death process considered, either a
      differential equation with two time delays or a differential equation with a
      state-dependent delay is obtained. Each of these is analysed in turn, for its
      linear stability. A sensitivity analysis of the parameters in this model shows
      which biochemical processes in the negative feedback most strongly affect the
      solutions.

PMID- 11453469
TI  - Modelling the growth of soil-borne fungi in response to carbon and nitrogen.
AB  - Growth of soil-borne fungi is poorly described and understood, largely because
      non-destructive observations on hyphae in soil are difficult to make.
      Mathematical modelling can help in the understanding of fungal growth. Except for
      a model by Paustian & Schnurer (1987a), fungal growth models do not consider
      carbon and nitrogen contents of the supplied substrate, although these nutrients
      have considerable effects on hyphal extension in soil. We introduce a fungal
      growth model in relation to soil organic matter decomposition dealing with the
      detailed dynamics of carbon and nitrogen. Substrate with a certain carbon :
      nitrogen ratio is supplied at a constant rate, broken down and then taken up by
      fungal mycelium. The nutrients are first stored internally in metabolic pools and
      then incorporated into structural fungal biomass. Standard mathematical
      procedures were used to obtain overall-steady states of the variables (implicitly
      from a cubic equation) and the conditions for existence. Numerical computations
      for a wide range of parameter combinations show that at most one solution for the
      steady state is biologically meaningful, specified by the conditions for
      existence. These conditions specify a constraint, namely that the 'energy' (in
      terms of carbon) invested in breakdown of substrate should be less than the
      'energy' resulting from breakdown of substrate, leading to a positive carbon
      balance. The biological interpretation of the conditions for existence is that
      for growth the 'energy' necessary for production of structural fungal biomass and
      for maintenance should be less than the mentioned positive carbon balance in the
      situation where all substrate is colonized. In summary, the analysis of this
      complicated fungal growth model gave results with a clear biological
      interpretation.

PMID- 11453470
TI  - A model of Gambian sleeping sickness with open vector populations.
AB  - A compartmental model of Gambian sleeping sickness is described that takes into
      account density-dependent migratory flows of infected flies. Equilibrium and
      stability theorems are given which show that with a basic reproduction number R0
      below unity, then in the absence of reinvasion the disease goes to extinction.
      However, even a low prevalence rate among reinvading flies can then bring about
      significant equilibrium prevalence rates among humans. For a set of realistic
      parameter values we show that even in the case of a virulent parasite that keeps
      infected individuals in the first stage for as little as 4 or 8 months (durations
      for which there would be extinction with no infected reinvading flies) there is a
      prevalence rate in the range 13.0-36.9%, depending on whether 1 or 2% of
      reinvading flies are infected. A rate of convergence of the population dynamics
      is introduced and is interpreted in terms of a halving time of the infected
      population. It is argued that the persistence and/or extension of Gambian
      sleeping sickness foci could be due either to a continuous reinvasion of infected
      flies or to slow dynamics.

PMID- 11453471
TI  - Analgesic, hemodynamic, and respiratory effects induced by caudal epidural
      administration of meperidine hydrochloride in mares.
AB  - OBJECTIVE: To determine the analgesic, hemodynamic, and respiratory effects
      induced by caudal epidural administration of meperidine hydrochloride in mares.
      ANIMALS: 7 healthy mares. PROCEDURE: Each mare received meperidine (5%; 0.8 mg/kg
      of body weight) or saline (0.9% NaCl) solution via caudal epidural injection on 2
      occasions. At least 2 weeks elapsed between treatments. Degree of analgesia in
      response to noxious electrical, thermal, and skin and muscle prick stimuli was
      determined before and for 5 hours after treatment. In addition, cardiovascular
      and respiratory variables were measured and degree of sedation (head position)
      and ataxia (pelvic limb position) evaluated. RESULTS: Caudal epidural
      administration of meperidine induced bilateral analgesia extending from the.
      coccygeal to S1 dermatomes in standing mares; degree of sedation and ataxia was
      minimal. Mean (+/- SD) onset of analgesia was 12 +/- 4 minutes after meperidine
      administration, and duration of analgesia ranged from 240 minutes to the entire
      300-minute testing period. Heart and respiratory rates, rectal temperature,
      arterial blood pressures, Hct, PaO2, PaCO2, pHa, total solids and bicarbonate
      concentrations, and base excess were not significantly different from baseline
      values after caudal epidural administration of either meperidine or saline
      solution. CONCLUSIONS AND CLINICAL RELEVANCE: Caudal epidural administration of
      meperidine induced prolonged perineal analgesia in healthy mares. Degree of
      sedation and ataxia was minimal, and adverse cardiorespiratory effects were not
      detected. Meperidine may be a useful agent for induction of caudal epidural
      analgesia in mares undergoing prolonged diagnostic, obstetric, or surgical
      procedures in the anal and perineal regions.

PMID- 11453472
TI  - Effects of enalaprilat on cardiorespiratory, hemodynamic, and hematologic
      variables in exercising horses.
AB  - OBJECTIVE: To determine the effects of IV administration of enalaprilat on
      cardiorespiratory and hematologic variables as well as inhibition of angiotensin
      converting enzyme (ACE) activity in exercising horses. ANIMALS: 6 adult horses.
      PROCEDURE: Horses were trained by running on a treadmill for 5 weeks. Training
      was continued throughout the study period, and each horse also ran 2 simulated
      races at 120% of maximum oxygen consumption. Three horses were randomly selected
      to receive treatment 1 (saline [0.9% NaCl] solution), and the remaining 3 horses
      received treatment 2 (enalaprilat; 0.5 mg/kg of body weight, IV) before each
      simulated race. Treatment groups were reversed for the second simulated race.
      Cardiorespiratory and hematologic data were obtained before, during, and
      throughout the 1-hour period after each simulated race. Inhibition of ACE
      activity was determined during and after each race in each horse. RESULTS:
      Exercise resulted in significant increases in all hemodynamic variables and
      respiratory rate. The pH and PO2 of arterial blood decreased during simulated
      races, whereas PCO2 remained unchanged. Systemic and pulmonary blood pressure
      measurements and arterial pH, PO2, and Pco2 returned to baseline values by 60
      minutes after simulated races. Enalaprilat inhibited ACE activity to < 25% of
      baseline activity without changing cardiorespiratory or blood gas values,
      compared with horses administered saline solution. CONCLUSIONS AND CLINICAL
      RELEVANCE: Enalaprilat administration almost completely inhibited ACE activity in
      horses without changing the hemodynamic responses to intense exercise and is
      unlikely to be of value in preventing exercise-induced pulmonary hemorrhage.

PMID- 11453473
TI  - Development of a technique for the in vivo assessment of flatulence in dogs.
AB  - OBJECTIVE: To develop a noninvasive method for the in vivo assessment of
      flatulence in dogs. ANIMALS: 8 adult dogs. PROCEDURE: Rectal gases were collected
      via a perforated tube held close to each dog's anus and attached to a monitoring
      pump fitted with a sensor that recorded hydrogen sulfide concentrations every 20
      seconds. Patterns of flatulence were monitored for 14 hours after feeding on 4
      days, and within- and between-dog variation was assessed over 4 hours on 4
      consecutive days. Rate of hydrogen sulfide production (flatulence index) and
      frequency and number of emissions were evaluated as potential indicators of
      flatus characteristics. An odor judge assigned an odor rating to each flatulence
      episode, and the relationship between that rating and hydrogen sulfide
      concentration was determined. RESULTS: Flatulence patterns varied within and
      between dogs. Variation was most pronounced for flatulence index; mean
      coefficients of variance within dogs over time and between dogs on each day were
      75 and 103%, respectively. Flatus with hydrogen sulfide concentrations > 1 parts
      per million could be detected by the odor judge, and severity of malodor was
      highly correlated with hydrogen sulfide concentration. Odor ratings were
      accurately predicted by use of the equation 1.51 X hydrogen sulfide
      concentration(0.28). CONCLUSIONS AND CLINICAL RELEVANCE: The technique described
      in this report appears to provide sensitive, reliable, and relevant data and will
      enable further studies of the factors that influence flatulence in dogs. Use of
      this technique also has the potential to aid in investigations of colonic
      physiology and pathology.

PMID- 11453474
TI  - Effects of subclinical pregnancy toxemia on immune responses in sheep.
AB  - OBJECTIVE: To determine the effects of moderate feed restriction, single or twin
      pregnancy, and subclinical pregnancy toxemia (PT) on immune responses of ewes.
      ANIMALS: 16 Sardinian ewes. PROCEDURE: Six weeks before lambing, ewes were
      assigned to 1 of 2 groups (n = 8/group) matched for number of fetuses, body
      condition score, and plasma glucose, non-esterified fatty acids (NEFA), and beta
      hydroxybutyrate (BHBA) concentrations, and feed intake was restricted for 1 of
      the groups. Cell-mediated immunity was evaluated in vivo and in vitro. Humoral
      immunity was evaluated in vivo by determining production of IgG antibodies
      against keyhole limpet hemocyanin (KLH). RESULTS: Four ewes developed subclinical
      PT (plasma BHBA concentration > 0.86 mmol/L without any clinical signs of
      disease). Whether feed was restricted and type of pregnancy (single vs twin) did
      not have any significant effects on cell-mediated and humoral immune responses.
      Ewes with subclinical PT had significantly lower in vitro proliferation of
      phytohemagglutinin-stimulated peripheral blood mononuclear cells and
      significantly lower values for KLH-specific IgG than did healthy ewes. Plasma
      BHBA and NEFA concentrations were negatively correlated with in vitro
      proliferation of peripheral blood mononuclear cells; plasma NEFA concentration
      was negatively correlated with values for KLH-specific IgG. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that subclinical PT may be associated with
      impairments in cell-mediated and humoral immune responses in sheep.

PMID- 11453475
TI  - Effects of ring diameter and wire tension on the axial biomechanics of four-ring
      circular external skeletal fixator constructs.
AB  - OBJECTIVE: To determine relative effects of ring diameter and wire tension on
      axial biomechanical properties of 4-ring circular external skeletal fixator
      constructs. SAMPLE POPULATION: 4-ring circular external skeletal fixator
      constructs and artificial bone models. PROCEDURE: 4-ring constructs were
      assembled, using 50-, 66-, 84-, or 118-mm-diameter rings. Two 1.6-mm-diameter
      fixation wires were attached to opposing surfaces of each ring at intersection
      angles of 90 degrees and placed through a gap-fracture bone model. Three examples
      of each construct were loaded in axial compression at 7 N/s to a maximum load of
      400 N at each of 4 wire tensions (0, 30, 60, and 90 kg). Response variables were
      determined from resulting load-displacement curves (construct stiffness, load at
      1 mm of displacement, displacement at 400 N). RESULTS: Ring diameter and wire
      tension had a significant effect on all response variables and had a significant
      interaction for construct stiffness and displacement at 400 N. Significant
      differences within all response variables were seen among all 4 ring diameters
      and all 4 wire tensions. As ring diameter increased, effect of increasing wire
      tension on gap stiffness and gap displacement at 400 N decreased. Ring diameter
      had a greater effect than wire tension on all response variables. CONCLUSIONS AND
      CLINICAL RELEVANCE: Although effects of wire tension decrease as ring diameter
      increases, placing tension on wires in larger ring constructs is important
      because these constructs are inherently less stiff. The differential contribution
      of ring diameter, wire tension, and their interactions must be considered when
      using circular external skeletal fixators.

PMID- 11453476
TI  - Use of an antineoepitope antibody for identification of type-II collagen
      degradation in equine articular cartilage.
AB  - OBJECTIVE: To develop an antibody that specifically recognizes collagenase
      cleaved type-II collagen in equine articular cartilage. SAMPLE POPULATION:
      Cartilage specimens from horses euthanatized for problems unrelated to the
      musculoskeletal system. PROCEDURE: A peptide was synthesized representing the
      carboxy- (C-) terminus (neoepitope) of the equine type-II collagen fragment
      created by mammalian collagenases. This peptide was used to produce a polyclonal
      antibody, characterized by western analysis for reactivity to native and
      collagenase-cleaved equine collagens. The antibody was evaluated as an
      antineoepitope antibody by ELISA, using peptides +/- an amino acid at the C
      terminus of the immunizing peptide. Collagen cleavage was assayed from equine
      articular cartilage cultured with interleukin-1 (IL-1), +/- a synthetic MMP
      inhibitor, BAY 12-9566. Cartilage specimens from osteoarthritic and nonarthritic
      joints were compared for antibody staining. RESULTS: An antibody, 234CEQ,
      recognized only collagenase-generated 3/4-length fragments of equine type-II
      collagen. This was a true antineoepitope antibody, as altering the C-terminus of
      the immunizing peptide significantly decreased competition for binding in an
      inhibition ELISA. The IL-1-induced release of type-II collagen fragments from
      articular cartilage was prevented with the MMP inhibitor. Cartilage from an
      osteoarthritic joint of a horse had increased staining with the 234CEQ antibody,
      compared with normal articular cartilage. CONCLUSIONS AND CLINICAL RELEVANCE: We
      generated an antineoepitope antibody recognizing collagenase-cleaved type-II
      collagen of horses. This antibody detects increases in type-II collagen cleavage
      in diseased equine articular cartilage. The 234CEQ antibody has the potential to
      aid in the early diagnosis of arthritis and to monitor treatment responses.

PMID- 11453477
TI  - Evaluation of phagocytosis, bactericidal activity, and production of superoxide
      anion, nitric oxide, and tumor necrosis factor-alpha in Kupffer cells of neonatal
      pigs.
AB  - OBJECTIVE: To evaluate the activity of Kupffer cells (KC) of control neonatal
      pigs and neonatal pigs treated with endotoxin and to compare activity of KC with
      that of pulmonary alveolar macrophages (PAM). SAMPLE POPULATION: Kupffer cells
      and PAM obtained from 24 neonatal pigs (7 to 10 days old). PROCEDURE: Pairs (n =
      7) of littermates served as treated (lipopolysaccharide [LPS]) or untreated pigs.
      Pigs were euthanatized 24 hours after treatment, and cells were isolated. Cells
      were obtained from 10 other neonatal pigs for other assays. Functional activity
      of cells was evaluated by use of in vitro assays to evaluate bactericidal
      activity, phagocytosis, and production of superoxide anion (SOA), nitric oxide
      (NO), and tumor necrosis factor-alpha (TNF-alpha). Each assay was repeated on
      cells obtained from 4 to 6 pigs. RESULTS: Phagocytic activity was similar in KC
      and PAM, but bactericidal activity and production of SDA and TNF-alpha was lower
      in KC. Neither KC nor PAM produced NO in response to LPS stimulation.
      Phagocytosis, bactericidal activity, and production of SOA were enhanced for KC
      obtained from neonatal pigs treated with LPS. The PAM from LPS-treated neonatal
      pigs had similar bactericidal activity to PAM obtained from untreated pigs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Functional capacity of KC is affected by
      endotoxin. This provides additional information of the role the liver plays in
      immune surveillance. In addition, the response of KC in neonatal pigs exposed to
      endotoxin is of value for understanding gram-negative bacterial sepsis, which is
      a major cause of mortality in neonatal pigs.

PMID- 11453478
TI  - Effect of cimetidine on pharmacokinetics of orally administered cyclosporine in
      healthy dogs.
AB  - OBJECTIVE: To describe the pharmacokinetics of cyclosporine (CyA) in healthy dogs
      after oral administration alone or in combination with orally administered
      cimetidine. ANIMALS: 10 healthy adult Beagles. PROCEDURE: Dogs were randomly
      assigned to receive CyA alone or CyA in combination with cimetidine. After a
      washout period of 2 weeks, dogs then received the alternate treatment. The CyA
      plus cimetidine treatment required administration of cimetidine (15 mg/kg of body
      weight, PO, q 8 h) for 8 days and administration of CyA (5 mg/kg, PO, q 24 h) on
      days 6 through 8. The CyA treatment alone required administration of CyA (5
      mg/kg, PO, q 24 h) for 3 days. On the third day of CyA administration during each
      treatment, blood samples were collected immediately before (time 0) and 0.5, 1,
      1.5, 2, 2.5, 3, 5, 7, 9, 11, 13, 15, 21, and 24 hours after initiating CyA
      administration. RESULTS: Time until maximum CyA concentration was significantly
      longer for CyA in combination with cimetidine. Assessment of estimated
      pharmacokinetic variables revealed a significantly faster rate of change in the
      distribution phase for CyA in combination with cimetidine. Maximum CyA
      concentration differed significantly among dogs but did not differ significantly
      between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of our data
      suggests that cimetidine may affect absorption of orally administered CyA, but
      overall, it does not affect the pharmacokinetics of CyA. There is considerable
      variability in the maximum concentration of CyA among dogs, and monitoring of
      blood concentrations of CyA during treatment is advised.

PMID- 11453479
TI  - Results of intradermal tests in horses without atopy and horses with atopic
      dermatitis or recurrent urticaria.
AB  - OBJECTIVE: To compare results of intradermal tests (IDT) for environmental
      allergens at 30 minutes and 4, 6, and 24 hours after injection in horses without
      atopy and horses with atopic dermatitis (AD) or recurrent urticaria (RU).
      ANIMALS: 22 horses without atopy, 10 horses with RU, and 7 horses with AD.
      PROCEDURE: In all horses, medical history was obtained, and results of physical
      examination, hematologic examination, serum biochemical analyses, examination of
      bronchoalveolar lavage fluid, and IDT with 73 allergens were examined. RESULTS:
      Horses with AD or RU had a significantly greater mean number of positive
      reactions for IDT, compared with horses without atopy. Horses with AD had a
      significantly greater number of positive reactions than horses without atopy in
      every allergen group at all time periods, except for molds at 4 and 24 hours.
      Horses with RU had a significantly greater number of positive reactions than
      horses without atopy in every allergen group, except for molds at 30 minutes and
      4 and 6 hours, trees at 4 and 6 hours, and grasses at 4 hours. CONCLUSIONS AND
      CLINICAL RELEVANCE: A significantly greater number of positive reactions for IDT
      in horses with AD or RU, compared with horses without atopy, provides evidence of
      type-I IgE-mediated hypersensitivity for these diseases. Evaluation of results of
      IDT performed in horses with AD or RU is useful in determining specific allergens
      for the formulation of immunotherapy along with providing identification of
      allergens that could be useful when creating avoidance strategies.

PMID- 11453480
TI  - Analysis of aqueous humor obtained from normal eyes of llamas and alpacas.
AB  - OBJECTIVE: To evaluate composition of aqueous humor obtained from normal eyes of
      llamas (Lama glama) and alpacas (Lama pacos). SAMPLE POPULATION: Aqueous humor
      obtained from 10 male llamas and 10 male alpacas. PROCEDURE: All animals had
      normal eyes, as determined by ocular examination. Aqueous humor samples were
      obtained via paracentesis of the anterior chamber of animals that were heavily
      sedated. Chemical analysis included measurement of concentrations of sodium,
      potassium, magnesium, chloride, bicarbonate, phosphorus, and glucose as well as
      osmolality and pH. RESULTS: With the exception of potassium concentrations,
      values for aqueous humor composition did not differ significantly between llamas
      and alpacas. Mean +/- SD values for llamas and alpacas, respectively, were:
      sodium, 154.7 +/- 2.1 and 152.7 +/- 2.1 mEq/L; potassium, 5.3 +/- 0.4 and 4.6 +/-
      0.4 mEq/L; magnesium, 1.8 +/- 0.1 and 1.7 +/- 0.1 mg/dl; chloride, 130.0 +/- 1.6
      and 127.0 +/- 3.3 mEq/L; bicarbonate, 19.2 +/- 1.5 and 20.2 +/- 2.3 mEq/L;
      phosphorous, 2.7 +/- 0.3 and 2.5 +/- 0.4 mg/dl; glucose, 80.3 +/- 3.9 and 80.8 +/
      7.3 mg/dl; total protein, 29.0 +/- 8.6 and 31.5 +/- 10.1 mg/dl; and osmolality,
      305.8 +/- 11.8 and 306.2 +/- 4.9 mOsm. The pH ranged from 7.5 to 8.0 for both
      species. Potassium concentrations were significantly higher in llamas than
      alpacas. CONCLUSIONS AND CLINICAL RELEVANCE: Except for potassium, composition of
      aqueous humor did not differ significantly between llamas and alpacas. Aqueous
      humor composition of llamas and alpacas is similar to that of other species that
      have been examined.

PMID- 11453481
TI  - Uptake of beta-carotene by ovarian and uterine tissues and effects on
      steroidogenesis during the estrous cycle in cats.
AB  - OBJECTIVES: To determine uptake of beta-carotene by ovarian and uterine tissues
      and influence of dietary beta-carotene on steroidogenesis and production of
      uterine protein during the estrous cycle in cats. ANIMALS: 56 female cats.
      PROCEDURE: Cats were fed diets containing 0, 0.4, 2, or 10 mg of beta-carotene
      daily for 8 weeks prior to detection of estrus. At time of observed estrus, all
      cats were manually induced to ovulate. Blood samples were obtained at estrus and
      every 2 days until day 14 after ovulation. On that day, cats underment
      laparotomy, and the ovaries and uterus were removed. Uterine contents were
      flushed, and luteal and endometrial tissues were obtained. RESULTS:
      Concentrations of beta-carotene in plasma and luteal and endometrial tissues
      increased in a dose-dependent manner. Concentrations of plasma progesterone were
      higher between days 6 and 10 after ovulation in cats fed diets containing beta
      carotene and continued to increase through day 14 after ovulation in cats fed a
      diet containing 10 mg of beta-carotene. Plasma concentration of estradiol-17beta
      also was higher between days 0 and 4 after ovulation in cats fed diets containing
      beta-carotene. Cats fed a diet containing 10 mg of beta-carotene had the highest
      plasma estradiol concentration. Total uterine protein concentration was higher in
      cats fed beta-carotene, compared with values for cats fed an unsupplemented diet.
      CONCLUSION AND CLINICAL RELEVANCE: Cats readily absorb beta-carotene. Increased
      concentrations of progesterone, estradiol, and uterine protein may provide more
      optimal ovarian function or a better uterine environment for embryonic survival
      and development.

PMID- 11453482
TI  - Barrier pressure at the gastroesophageal junction in anesthetized dogs.
AB  - OBJECTIVE: To evaluate the effect of body position on barrier pressure at the
      gastroesophageal junction in anesthetized Greyhounds and to assess alterations in
      barrier pressure following gastropexy. ANIMALS: 8 adult Greyhounds. PROCEDURE:
      Barrier pressure at the gastroesophageal junction was measured by fast (1 cm/s)
      and slow (1 cm/10 s) withdrawal of a subminiature strain gauge transducer through
      the gastroesophageal junction in 8 anesthetized dogs. The effect of body position
      was measured. Each dog then was placed in right-lateral recumbency, and
      gastropexy was performed in the left flank. Additional measurements were obtained
      1, 5, 10, 20, and 30 minutes after gastropexy. RESULTS: Barrier pressure for dogs
      positioned in sternal recumbency (mean +/- SEM, 1.1 +/- 0.53 mm Hg) was
      significantly less than for dogs positioned in right lateral or left lateral
      recumbency. Following gastropexy, there was a steady increase in barrier
      pressure. Thirty minutes after gastropexy, barrier pressure was significantly
      higher (13.36 +/- 3.46 mm Hg), compared with the value before surgery.
      CONCLUSIONS AND CLINICAL RELEVANCE: Barrier pressure in anesthetized dogs is
      highly variable and influenced by body position. This is most likely the result
      of anatomic interrelationships between the diaphragm, stomach, and terminal
      portion of the esophagus. Gastropexy also increases barrier pressure in the
      immediate postoperative period, which may be clinically relevant in terms of
      understanding how resolution of gastroesophageal reflux disease associated with
      hiatal hernia may be affected by gastropexy combined with hernia reduction.

PMID- 11453483
TI  - Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing
      propofol-isoflurane anesthesia.
AB  - OBJECTIVE: To compare 3 dose levels of medetomidine and dexmedetomidine for use
      as premedicants in dogs undergoing propofol-isoflurane anesthesia. ANIMALS: 6
      healthy Beagles. PROCEDURE: Dogs received medetomidine or dexmedetomidine
      intravenously at the following dose levels: 0.4 microg of medetomidine or 0.2
      microg of dexmedetomidine/kg of body weight (M0.4/D0.2), 4.0 microg of
      medetomidine or 2.0 microg of dexmedetomidine/kg (M4/D2), and 40 microg of
      medetomidine or 20 microg of dexmedetomidine/kg (M40/D20). Sedation and analgesia
      were scored before induction. Anesthesia was induced with propofol and maintained
      with isoflurane. End-tidal isoflurane concentration, heart rate, and arterial
      blood pressures and gases were measured. RESULTS: Degrees of sedation and
      analgesia were significantly affected by dose level but not drug. Combined mean
      end-tidal isoflurane concentration for all dose levels was higher in dogs that
      received medetomidine, compared with dexmedetomidine. Recovery time was
      significantly prolonged in dogs treated at the M40/D20 dose level, compared with
      the other dose levels. After induction, blood pressure decreased below reference
      range and heart rate increased in dogs treated at the M0.4/D0.2 dose level,
      whereas blood pressure was preserved in dogs treated at the M40/D20 dose level.
      However, dogs in these latter groups developed profound bradycardia and mild
      metabolic acidosis during anesthesia. Treatment at the M4/D2 dose level resulted
      in more stable cardiovascular effects, compared with the other dose levels. In
      addition, PaCO2 was similar among dose levels. CONCLUSIONS AND CLINICAL
      RELEVANCE: Dexmedetomidine is at least as safe and effective as medetomidine for
      use as a premedicant in dogs undergoing propofol-isoflurane anesthesia.

PMID- 11453484
TI  - Metabolic changes and induction of hepatic lipidosis during feed restriction in
      llamas.
AB  - OBJECTIVES: To determine whether feed restriction induces hepatic lipidosis (HL)
      in llamas and to evaluate the metabolic changes that develop during feed
      restriction. ANIMALS: 8 healthy adult female llamas. PROCEDURE: Llamas were fed
      grass hay at a rate of 0.25% of their body weight per day for 13 to 28 days.
      Llamas were monitored by use of clinical observation, serum biochemical analyses,
      and ultrasound-guided liver biopsies. RESULTS: All 8 llamas lost weight and
      mobilized fat. Five llamas developed HL, including 4 that were nursing crias.
      During the period of feed restriction, mean serum concentration of bile acids and
      activities of aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), and
      gamma-glutamyl transferase (GGT) were significantly higher in llamas that
      developed HL, compared with llamas that did not. Mean insulin-to-cortisol
      concentration ratios were lower in llamas with HL before and up to 7 days of feed
      restriction, compared with those that did not develop HL. CONCLUSIONS AND
      CLINICAL RELEVANCE: HL in llamas may be induced by severe feed restriction,
      particularly in the face of increased energy demand. Llamas with weight loss
      attributable to inadequate dietary intake may develop biochemical evidence of
      hepatopathy and HL. Increases in serum concentration of bile acids and activities
      of GGT, AST, and SDH may indicate the development of HL in llamas and identify
      affected animals for aggressive therapeutic intervention.

PMID- 11453485
TI  - Changes in molecular expression of aggrecan and collagen types I, II, and X,
      insulin-like growth factor-I, and transforming growth factor-beta1 in articular
      cartilage obtained from horses with naturally acquired osteochondrosis.
AB  - OBJECTIVE: To determine molecular changes in the expression of insulin-like
      growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) in
      horses with osteochondrosis, and to characterize expression of matrix aggrecan
      and collagen types I, II, and X in articular cartilage of affected joints. SAMPLE
      POPULATION: Articular cartilage from affected stifle or shoulder joints of 11
      horses with naturally acquired osteochondrosis and corresponding joints of 11
      clinically normal horses. PROCEDURE: Harvested specimens were snap frozen in
      liquid nitrogen, and total RNA was isolated. Specimens were fixed in 4%
      paraformaldehyde for histologic examinations. Expression of matrix molecules was
      assessed by analysis of northern blots and in situ hybridization, using equine
      specific cDNA probes and riboprobes, respectively. Expression of IGF-I and TGF
      beta1 was assessed by use of noncompetitive quantitative polymerase chain
      reaction, in situ hybridization, and immunohistochemical analysis. RESULTS:
      Cartilage obtained from osteochondrosis lesions had significantly greater
      expression of IGF-I, compared with normal cartilage. Expression of TGF-beta1 and
      collagen type I were higher, but not significantly so, in affected tissues.
      Expression of aggrecan or collagen types II and X did not differ between affected
      and clinically normal cartilage. CONCLUSIONS AND CLINICAL RELEVANCE: Increased
      expression of growth factors and collagen type I was found in cartilage from
      osteochondrosis lesions. However, this probably reflects a healing response to
      injured tissue rather than a primary alteration. Therefore, methods aimed at
      altering concentrations of growth factors in cartilage of growing horses would be
      unlikely to alter the incidence or progress of the disease.

PMID- 11453486
TI  - Relationship between degree of viremia and disease manifestation in calves with
      experimentally induced bovine viral diarrhea virus infection.
AB  - OBJECTIVE: To compare degree of viremia and disease manifestations in calves with
      type-I and -II bovine viral diarrhea virus (BVDV) infection. ANIMALS: 16 calves.
      PROCEDURE: Colostrum-deprived calves obtained immediately after birth were
      assigned to 1 control and 3 treatment groups (4 calves/group). Calves in
      treatment groups were inoculated (day 0) by intranasal instillation of 10(7)
      median tissue culture infective dose BVDV 890 (type II), BVDV 7937 (type II), or
      BVDV TGAN (type I). Blood cell counts and virus isolation from serum and
      leukocytes were performed daily, whereas degree of viremia was determined
      immediately before and 4, 6, 8, and 12 days after inoculation. Calves were
      euthanatized on day 12, and pathologic, virologic, and immunohistochemical
      examinations were performed. RESULTS: Type-II BVDV 890 induced the highest degree
      of viremia, and type-I BVDV TGAN induced the lowest. Virus was isolated more
      frequently and for a longer duration in calves inoculated with BVDV 890. A
      parallel relationship between degree of viremia and rectal temperature and an
      inverse relationship between degree of viremia and blood cell counts was
      observed. Pathologic and immunohistochemical examinations revealed more
      pronounced lesions and more extensive distribution of viral antigen in calves
      inoculated with type-II BVDV. CONCLUSIONS AND CLINICAL RELEVANCE: Degree of
      viremia induced during BVDV infection is associated with severity of clinical
      disease. Isolates of BVDV that induce a high degree of viremia may be more
      capable of inducing clinical signs of disease. Strategies (eg, vaccination) that
      reduce viremia may control clinical signs of acute infection with BVDV.

PMID- 11453487
TI  - Experimental induction of chronic borreliosis in adult dogs exposed to Borrelia
      burgdorferi-infected ticks and treated with dexamethasone.
AB  - OBJECTIVE: To develop a method to experimentally induce Borrelia burgdorferi
      infection in young adult dogs. ANIMALS: 22 healthy Beagles. PROCEDURE: All dogs
      were verified to be free of borreliosis. Twenty 6-month-old dogs were exposed to
      Borrelia burgdorferi-infected adult ticks and treated with dexamethasone for 5
      consecutive days. Two dogs not exposed to ticks were treated with dexamethasone
      and served as negative-control dogs. Clinical signs, results of microbial culture
      and polymerase chain reaction (PCR) testing, immunologic responses, and gross and
      histologic lesions were evaluated 9 months after tick exposure. RESULTS:
      Predominant clinical signs were episodic pyrexia and lameness in 12 of 20 dogs.
      Infection with B burgdorferi was detected in microbial cultures of skin biopsy
      specimens and various tissues obtained during necropsy in 19 of 20 dogs and in
      all 20 dogs by use of a PCR assay. All 20 exposed dogs seroconverted and
      developed chronic nonsuppurative arthritis. Three dogs also developed mild focal
      meningitis, 1 dog developed mild focal encephalitis, and 18 dogs developed
      perineuritis or rare neuritis. Control dogs were seronegative, had negative
      results for microbial culture and PCR testing, and did not develop lesions.
      CONCLUSIONS AND CLINICAL RELEVANCE: Use of this technique successfully induced
      borreliosis in young dogs. Dogs with experimentally induced borreliosis may be
      useful in evaluating vaccines, chemotherapeutic agents, and the pathogenesis of
      borreliosis-induced arthritis.

PMID- 11453488
TI  - Radiometric assessment of hexose monophosphate shunt capacity in erythrocytes of
      rhinoceroses.
AB  - OBJECTIVES: To measure metabolic rates of the hexose monophosphate shunt (HMPS)
      in erythrocytes of rhinoceroses, and to test the hypothesis that low
      concentrations of endogenous ATP in erythrocytes impair HMPS capacity, thereby
      increasing susceptibility to oxidant-induced hemolysis. ANIMALS: 13 black and 3
      white rhinoceroses, free-ranging in several regions of southern Africa, and 1
      Sumatran rhinoceros in US captivity. PROCEDURE: HMPS fluxes were measured in
      rhinoceros erythrocytes with carbon-labeled glucose in the presence and absence
      of known HMPS activators. RESULTS: Compared with values for human erythrocytes,
      mean basal state HMPS fluxes were appreciably lower (22 to 46%) in all 3
      rhinoceros species studied. Shunt activators increased HMPS rates approximately 5
      fold over basal rates in rhinoceros erythrocytes, compared with increases in
      humans of 10-fold with ascorbate and 15-fold with methylene blue. Stimulated HMPS
      rates in human erythrocytes were quantitatively 5- to 10-times greater than those
      observed in rhinoceros erythrocytes. Overall HMPS catabolic rates were completely
      independent of intracellular ATP concentrations. CONCLUSIONS AND CLINICAL
      RELEVANCE: HMPS glycolytic and recycling rates and responses to activators are
      inherently low in erythrocytes from 3 species of rhinoceros, likely contributing
      to (but not solely responsible for) the high susceptibility of black rhinoceroses
      to oxidant-induced hemolysis. Slow erythrocyte HMPS capacities were independent
      of intracellular ATP concentrations, invalidating a current hypothesis regarding
      the pathogenesis of hemolytic anemia in captive black rhinoceroses. Limitations
      in HMPS capacities emphasize the importance of protecting rhinoceroses from
      exposure to drugs, chemicals, toxins, foodstuffs, and other conditions known to
      increase production of oxidizing metabolites, reactive oxygen species, and free
      radicals.

PMID- 11453489
TI  - Effect of alpha-tocopheryl acetate supplementation on vitamin E concentrations in
      Greyhounds before and after a race.
AB  - OBJECTIVES: To determine effect of alpha-tocopherol supplementation on serum
      vitamin E concentrations in Greyhounds before and after a race. ANIMALS: 8 adult
      racing Greyhounds. PROCEDURE: Dogs were given 2 capsules of alpha-tocopheryl
      acetate (total, 680 units [0.5 g]) with food that contained < or = 15 mg of
      vitamin E/kg each morning for 7 days. Dogs were exercised in a 30 X 30-m grass
      paddock for 15 minutes twice a day and raced for 500 m twice a week. Blood
      samples were collected before and 5 minutes after a race, before supplementation
      was begun, and after 7 days of supplementation. Blood and diet samples were
      analyzed for tocopherols and alpha-tocopheryl acetate. RESULTS: Before
      supplementation, serum alpha-tocopherol concentration after racing (mean +/- SD,
      6.7 +/- 2.4 mg/L ) was significantly lower than before racing (12.2 +/- 3.1
      mg/L). After supplementation, alpha-tocopherol concentrations were significantly
      higher overall, although values obtained before (26.6 +/- 5.2 mg/L) and after
      (29.8 +/- 3.6 mg/L) racing were not significantly different. CONCLUSIONS AND
      CLINICAL RELEVANCE: Supplementation with alpha-tocopheryl acetate increased serum
      alpha-tocopherol concentrations and eliminated the decrease in alpha-tocopherol
      concentration that was detected after a race, which may decrease oxidation during
      exercise and improve performance or recovery.

PMID- 11453490
TI  - Direct and indirect contact rates among beef, dairy, goat, sheep, and swine herds
      in three California counties, with reference to control of potential foot-and
      mouth disease transmission.
AB  - OBJECTIVE: To estimate direct and indirect contact rates on livestock facilities
      and distance traveled between herd contacts. SAMPLE POPULATION: 320 beef, dairy,
      goat, sheep, and swine herds, 7 artificial insemination technicians, 6 hoof
      trimmers, 15 veterinarians, 4 sales yard owners, and 7 managers of livestock
      related companies within a 3-county region of California. PROCEDURE: A
      questionnaire was mailed to livestock producers, and personal and telephone
      interviews were conducted with individuals. RESULTS: Mean monthly direct contact
      rates were 2.6, 1.6, and 2.0 for dairies with < 1,000, 1,000 to 1,999, and > or =
      2,000 cattle, respectively. Mean indirect contact rates on dairies ranged from
      234 to 743 contacts/mo and increased by 1 contact/mo as herd size increased by
      4.3. Mean direct monthly contact rate for beef herds was 0.4. Distance traveled
      by personnel and vehicles during a 3-day period ranged from 58.4 to 210.4 km. Of
      livestock arriving at sales yards, 7% (500/7,072) came from > or = 60 km away,
      and of those sold, 32% (1,180/3,721) were destined for a location > or = 60 km
      away. Fifty-five percent (16/29) of owners of large beef herds observed deer or
      elk within 150 m of livestock at least once per month. CONCLUSIONS AND CLINICAL
      RELEVANCE: Direct and indirect contacts occur on livestock facilities located
      over a wide geographic area and at a higher frequency on larger facilities.
      Knowledge of contact rates may be useful for planning biosecurity programs at the
      herd, state, and national levels and for modeling transmission potential for foot
      and-mouth disease virus.

PMID- 11453491
TI  - Thyroid function testing in Greyhounds.
AB  - OBJECTIVE: To evaluate thyroid function in healthy Greyhounds, compared with
      healthy non-Greyhound pet dogs, and to establish appropriate reference range
      values for Greyhounds. ANIMALS: 98 clinically normal Greyhounds and 19 clinically
      normal non-Greyhounds. PROCEDURES: Greyhounds were in 2 groups as follows: those
      receiving testosterone for estrus suppression (T-group Greyhounds) and those not
      receiving estrus suppressive medication (NT-group Greyhounds). Serum thyroxine
      (T4) and free thyroxine (fT4) concentrations were determined before and after
      administration of thyroid-stimulating hormone (TSH) and thyroid-releasing hormone
      (TRH). Basal serum canine thyroid stimulating hormone (cTSH) concentrations were
      determined on available stored sera. RESULTS: Basal serum T4 and fT4
      concentrations were significantly lower in Greyhounds than in non-Greyhounds.
      Serum T4 concentrations after TSH and TRH administration were significantly lower
      in Greyhounds than in non-Greyhounds. Serum fT4 concentrations after TSH and TRH
      administration were significantly lower in NT-group than T-group Greyhounds and
      non-Greyhounds. Mean cTSH concentrations were not different between Greyhounds
      and non-Greyhounds. CONCLUSIONS AND CLINICAL RELEVANCE: Previously established
      canine reference range values for basal serum T4 and fT4 may not be appropriate
      for use in Greyhounds. Greyhound-specific reference range values for basal serum
      T4 and fT4 concentrations should be applied when evaluating thyroid function in
      Greyhounds. Basal cTSH concentrations in Greyhounds are similar to non-Greyhound
      pet dogs.

PMID- 11453492
TI  - Results of hyperamplification of centrosomes in naturally developing tumors of
      dogs.
AB  - OBJECTIVE: To evaluate results of centrosome hyperamplification in naturally
      developing tumors of dogs. SAMPLE POPULATION: Tumor specimens from 9 dogs with
      tumors (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myxosarcoma, and mammary
      gland tumor) and 2 canine osteosarcoma cell lines. PROCEDURE: 3 antibodies for
      centrosome proteins (ie, anti-gamma-tubulin, anti-BRCA1, and anti-pericentrin)
      were used for immunohistochemical analysis. Double immunostaining for centrosomes
      was used to confirm the specificity of these antibodies for centrosomes.
      Mutational analysis of the canine p53 gene was carried out by polymerase chain
      reaction-single-strand conformation polymorphism analysis, and expression of
      canine MDM2 protein was evaluated by use of immunohistochemical analysis, using
      anti-MDM2 antibody. RESULTS: Immunohistochemical analysis of dog osteosarcoma
      cell lines with apparent aneuploidy revealed frequent hyperamplification of
      centrosomes in the osteosarcoma cell lines. Similar hyperamplified centrosomes
      were detected in the tumor tissues from all of the 9 tumors. The frequency of
      cells with hyperamplified centrosomes (3 to 20/cell) in each tumor tissue ranged
      from 9.50 to 48.1%, whereas centrosome hyperamplification was not observed in
      normal lymph nodes from these dogs. In 8 of the 9 tumors, mutation of p53 gene or
      overexpression of MDM2, or both, was detected. CONCLUSIONS AND CLINICAL
      RELEVANCE: Various types of naturally developing tumors in dogs often have
      hyperamplification of centrosomes associated with chromosome instability.
      Hyperamplification of centrosomes is a novel tumor marker for use in cytologic
      and histologic examinations of clinical specimens obtained from dogs.

PMID- 11453493
TI  - Evaluation of collagenase activity, matrix metalloproteinase-8, and matrix
      metalloproteinase-13 in horses with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To determine collagenase activity and evaluate matrix
      metalloproteinase (MMP)-8 and MMP-13 in horses with chronic obstructive pulmonary
      disease (COPD). ANIMALS: 12 horses with COPD and 12 healthy control horses.
      PROCEDURE: Collagenase activity was determined by use of an assay for degradation
      of type-I collagen. Western immunoblot analysis was used to identify interstitial
      collagenases MMP-8 and MMP-13 in tracheal epithelial lining fluid (TELF).
      Immunocytochemistry and in situ hybridization were used to determine cellular
      expression of these 2 collagenases in cells in bronchoalveolar lavage fluid
      (BALF). RESULTS: Collagenase activity was approximately 7 times higher in samples
      obtained from horses with COPD, compared with control horses. During stabling,
      horses with COPD had significantly higher collagenase activity than after being
      maintained on summer pasture, when activity was similar to that of control
      horses. Immunoreactivity of MMP-8 and MMP-13 was significantly increased in TELF
      of horses with COPD, compared with healthy horses. In TELF, a positive
      correlation was detected between immunoreactivity of MMP-8 and MMP-13 and the
      amount of degradation of type-I collagen. Macrophages and epithelial cells were
      the major cellular sources of MMP-8 and MMP-13. CONCLUSIONS AND CLINICAL
      RELEVANCE: Increased collagenase activity in TELF indicates active ongoing
      disease and, thus, may reflect lung tissue changes in horses with COPD.
      Measurements of collagenase activity and MMP immunoreactivity may provide
      additional diagnostic tools to identify the active phase of chronic lung disease.

PMID- 11453494
TI  - Effects of a bioactive glass on healing of closed skin wounds in dogs.
AB  - OBJECTIVE: To determine effects of intraincisional bioactive glass on healing of
      sutured skin wounds in dogs. ANIMALS: 9 purpose-bred mature female Beagles.
      PROCEDURE: 3 small matched bilateral (treated vs control) full-thickness truncal
      skin incisions were made and sutured. Treated wounds received intraincisional
      particulate bioactive glass prior to closure. Laser Doppler perfusion imaging was
      used to assess percentage change in tissue perfusion 3 and 5 days after incision
      on 1 set of 2 matched wounds, and skin and subcutaneous tissue-cutaneous trunci
      breaking strength were assessed at 5 days. The other 2 sets of wounds were used
      for histologic evaluation at 5 and 21 days, respectively. RESULTS: Subjective
      signs of gross inflammatory reaction were not detected in treated or control
      wounds. At 5 days, median subcutaneous tissue-cutaneous trunci breaking strength
      was significantly higher in treated wounds than in control wounds-(188.75 vs
      75.00 g). At 5 days, median scores were significantly higher for neutrophils (1
      vs 0), macrophages (2 vs 1), and necrosis (1 vs 0) for treated wounds than for
      control wounds. At 21 days, median macrophage scores were significantly higher
      for treated wounds than for control wounds (2 vs 1). CONCLUSIONS AND CLINICAL
      RELEVANCE: Bioactive glass in soft tissues does not cause a gross inflammatory
      reaction but causes an increase in histologic signs of inflammation, which
      decreases with time. Bioactive glass has potential for increasing tissue
      strength. Increased subcutaneous breaking strength could be beneficial in
      treating wounds in which early healing strength is needed.

PMID- 11453495
TI  - Effect of maternal immunity on the immune response to oral vaccination against
      rabies in young foxes.
AB  - OBJECTIVE: To determine effect of maternal antibodies on immune response to oral
      vaccination against rabies in young foxes. ANIMALS: 250 cubs from 48 vixens.
      PROCEDURE: Sera were obtained from cubs of 36 vaccinated (maternally vaccinated
      [MV+]) and 12 nonvaccinated (MV-) vixens between 23 and 71 days of age and tested
      for neutralizing antibodies. Seventy-one MV+ cubs and 33 MV-cubs were vaccinated
      orally with modified-live virus vaccine SAD B19. Geometric mean titer (GMT) was
      determined in these cubs approximately 21, 39, and 57 days after vaccination. In
      a subsequent experiment, 10 vaccinated MV+ cubs, 6 vaccinated MV- cubs, and 6
      control cubs were challenge inoculated with virulent rabies virus approximately
      100 days after vaccination. RESULTS: Serum GMT of nonvaccinated MV cubs (0.23
      U/ml) was significantly greater than that of non-vaccinated MV- cubs (0.15 U/ml).
      The GMT of vaccinated MV+ cubs 21, 39, and 57 days after vaccination were 2.85,
      2.11, and 0.79 U/ml, respectively, and were significantly less than those of
      vaccinated MV- cubs (12.19, 6.76, and 4.02 U/ml, respectively). All challenge
      inoculated cubs with GMT < 0.5 U/ml succumbed to rabies. CONCLUSION AND CLINICAL
      RELEVANCE: Partially impaired immune response in cubs < 8 weeks old from
      vaccinated vixens causes insufficient protection against rabies. Inhibition of
      the immune response persists longer than the period during which maternal
      antibodies are detectable. Thus, oral vaccination campaigns for young foxes in
      areas where vaccination has been performed need to be reconsidered.

PMID- 11453496
TI  - Efficacy of computerized discrimination between structure-related and non
      structure-related echoes in ultrasonographic images for the quantitative
      evaluation of the structural integrity of superficial digital flexor tendons in
      horses.
AB  - OBJECTIVE: To evaluate effectiveness of computerized discrimination between
      structure-related and non-structure-related echoes in ultrasonographic images for
      quantitative evaluation of tendon structural integrity in horses. SAMPLE
      POPULATION: 4 superficial digital flexor tendons (2 damaged tendons, 2 normal
      tendons). PROCEDURE: Transverse ultrasonographic images that precisely matched
      histologic sections were obtained in fixed steps along the long axis of each
      tendon. Distribution, intensity, and delineation of structure-related echoes,
      quantitatively expressed as the correlation ratio and steadiness ratio , were
      compared with histologic findings in tissue that was normal or had necrosis,
      early granulation, late granulation, early fibrosis, or inferior repair. RESULTS:
      In normal tendon, the even distribution of structure-related echoes with high
      intensity and sharp delineation yielded high correlation ratio and steadiness
      ratio. In areas of necrosis, collapsed endotendon septa yielded solid but blurred
      structure-related echoes (high correlation ration and low steadiness ratio). In
      early granulation tissue, complete lack of organization caused zero values for
      both ratios. In late granulation tissue, reorganization and swollen endotendon
      septa yielded poorly delineated structure-related echoes (high correlation ratio,
      low steadiness ratio). In early fibrosis, rearrangement of bundles resulted in
      normal correlation ration and slightly low steadiness ratio. In inferior repair,
      the almost complete lack of structural reorganization resulted in heterogeneous
      poorly delineated low-intensity echoes (low correlation ratio and steadiness
      ratio). CONCLUSIONS AND CLINICAL RELEVANCE: The combination of correlation ratio
      and steadiness ratio accurately reflects histopathologic findings, making
      computerized correlation of ultrasonographic images an efficient tool for
      quantitative evaluation of tendon structural integrity.

PMID- 11453497
TI  - Evaluation of hoof wall surface temperature as an index of digital vascular
      perfusion during the prodromal and acute phases of carbohydrate-induced laminitis
      in horses.
AB  - OBJECTIVE: To evaluate the use of hoof wall surface temperature (HWST) as an
      indirect indicator of digital perfusion and to describe HWST patterns during the
      prodromal and acute phases of carbohydrate-induced laminitis in horses. ANIMALS:
      30 adult horses without foot abnormalities. PROCEDURES: Three experiments were
      performed. In the first, HWST was measured in 2 groups of horses acclimatized to
      hot (n = 6), or cold (6) environments and exposed to cold (15 C) ambient
      temperature. In the second experiment, HWST were measured in both forefeet of 6
      horses before and after application of a tourniquet to 1 forefoot to induce
      vascular occlusion. In the third experiment, HWST were recorded in 12 horses
      before and during the prodromal and acute phases of carbohydrate-induced
      laminitis. RESULTS: Mean HWST of hot-acclimatized cold-challenged horses was
      significantly less than that of cold-acclimatized cold-challenged horses at all
      times. Transient episodes of high HWST were observed during prolonged cold
      induced vasoconstriction. Hoof wall surface temperature significantly decreased
      during arterial occlusion and increased during reperfusion. Digital hypothermia
      was observed during the prodromal phase of carbohydrate-induced laminitis.
      CONCLUSIONS AND CLINICAL RELEVANCE: Determination of HWST is a valid technique to
      evaluate digital perfusion under appropriate controlled conditions in horses.
      Digital hypothermia detected during the prodromal phase of laminitis is
      consistent with decreased digital vascular perfusion or metabolic activity. If
      administered to horses during the prodromal phase, agents that enhance digital
      perfusion may prevent development of laminitis.

PMID- 11453498
TI  - Treadmill study of the range of back movement at the walk in horses without back
      pain.
AB  - OBJECTIVE: To evaluate back movement during walking in horses. ANIMALS: 22 adult
      horses with no history or signs of back pain. PROCEDURE: 3-dimensional movements
      of markers on the hooves, head, and back were measured with a motion analysis
      system while the horses were walking on a treadmill. The positions of markers on
      the hooves, head, and the skin above the spinous processes of T5, T10, T16, L3,
      and 2 sacral vertebrae were recorded. From a minimum of 6 walking motion
      cycles/horse, marker movement and the time of occurrence of minimum and maximum
      marker positions within the motion cycle were determined. Angles were calculated
      between the markers on the head, T16, and S4 or S5 and between the markers on T5,
      T16, and S4 or S5. RESULTS: Lateral back movement was maximal at L3, where it
      reached (mean +/- SD) 3.5 +/- 0.8% of the horses' height at the withers. Maximum
      dorsoventral back movement was found at the sacrum, where it reached 4.7 +/- 1.3%
      of the height at the withers. In the horizontal plane, the angle between T5, T16,
      and S4 or S5 was altered by 11 +/- 2.5 degrees during the motion cycle. In the
      sagittal plane, the angle between the head, T16, and S4 or S5 was altered by 7 +/
      3 degrees. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study may be used
      as basic kinematic reference data for evaluation of back movement in horses.

PMID- 11453499
TI  - Susceptibility of ducks to avian pneumovirus of turkey origin.
AB  - OBJECTIVE: To determine the susceptibility of ducks to avian pneumovirus (APV) of
      turkey origin. ANIMALS: 30 Pekin ducks that were 2 weeks old. PROCEDURE: Ducks
      were assigned to 3 groups (10 ducks/group). Ducks of groups 1 and 2 were
      inoculated (day 0) with 200 microl of cell-culture fluid containing APV of turkey
      origin (10(5.5) median tissue-culture infective dose/ml) by the oculonasal (group
      1) or oral (group 2) route. Ducks of group 3 served as noninoculated control
      birds. Two ducks from each group were euthanatized 3, 6, 9, 15, and 21 days after
      inoculation. Blood samples, tissue samples from the lungs, trachea, nasal
      turbinates, duodenum, diverticulum vitellinum (Meckel's diverticulum), and cecum,
      and swab specimens from the choana, cloaca, and trachea were obtained from all
      birds during necropsy and examined for APV by use of reverse transcriptase
      polymerase chain reaction (RT-PCR), virus isolation, and histologic examination.
      Blood samples also were examined for APV antibodies, using an ELISA. RESULTS:
      Tissue samples obtained up to 21 days after inoculation had positive results when
      tested by use of RT-PCR. Virus was isolated from nasal turbinates of birds
      inoculated via the oculonasal route. Serum samples obtained 15 and 21 days after
      inoculation had positive results when tested for APV-specific antibody. Clinical
      signs of disease were not observed in ducks inoculated with APV of turkey origin.
      CONCLUSIONS AND CLINICAL RELEVANCE: Ducks inoculated with APV of turkey origin
      may not develop clinical signs of disease, but they are suspected to play a role
      as nonclinical carriers of APV.

PMID- 11453500
TI  - Use of a monovalent leptospiral vaccine to prevent renal colonization and urinary
      shedding in cattle exposed to Leptospira borgpetersenii serovar hardjo.
AB  - OBJECTIVE: To determine whether a monovalent Leptospira borgpetersenii serovar
      hardjo (type hardjobovis) vaccine commercially available in Australia, New
      Zealand, Ireland, and the United Kingdom would protect cattle from renal
      colonization and urinary shedding when exposed to a US strain of Leptospira
      borgpetersenii serovar hardjo. ANIMALS: 24 Hereford heifers that lacked
      detectable antibodies against serovar hardjo. PROCEDURE: Heifers received 2
      doses, 4 weeks apart, of the commercial hardjo vaccine (n = 8) or a monovalent US
      reference hardjo vaccine (8) or were not vaccinated (controls; 8). Heifers were
      challenged 16 weeks later by intraperitoneal inoculation or conjunctival
      instillation. Serum antibody titers were measured weekly, and urine samples were
      examined for leptospires. Heifers were euthanatized 11 to 14 weeks after
      challenge, and kidney tissue was examined for evidence of colonization. RESULTS:
      All 8 heifers vaccinated with the reference vaccine were found to be shedding
      leptospires in their urine and had evidence of renal colonization. All 4 control
      heifers challenged by conjunctival instillation and 2 of 4 control heifers
      challenged by intraperitoneal inoculation shed leptospires in their urine, and
      all 8 had evidence of renal colonization. In contrast, leptospires were not
      detected in the urine or tissues of any of the 8 heifers that received the
      commercial hardjo vaccine. Heifers that received the commercial hardjo vaccine
      had significantly higher antibody titers than did heifers that received the
      reference vaccine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      cattle that received 2 doses of the commercial hardjo vaccine were protected
      against renal colonization and urinary shedding when challenged with L
      borgpetersenii serovar hardjo strain 203 four months after vaccination.

PMID- 11453501
TI  - Sense of smell in long-standing nasal polyposis.
AB  - An impaired sense of smell is a common complaint in patients with nasal
      polyposis, and hyposmia is usually attributed to obstruction of the nasal
      airways. The duration of nasal polyposis and nasal surgery may also affect
      olfaction. It has been shown that aging and chronic rhinitis both impair
      olfaction. The aim of our study was to evaluate the sense of smell in patients
      who had had nasal polyposisfor at least 20 years. The olfactory threshold was
      assessed with a commercially available odor detection threshold test. The
      threshold of 19 (46%) of 41 patients was greater than the age-related upper 95%
      reference limit. In a forward stepwise multiple regression analysis of all the
      polyposis patients, the degree of opacity of ethmoidal sinuses seen in computed
      tomography (CT), polyposis visible in anterior rhinoscopy, total nasal
      resistance, and gender had a significant association with olfactory threshold.

PMID- 11453502
TI  - The effects of endoscopic sinus surgery on the nasal cycle as assessed by
      acoustic rhinometry.
AB  - Previous studies have demonstrated that acoustic rhinometry (AR) has a
      considerable utility in measuring nasal patency and in detecting the nasal cycle.
      This study was performed in 10 patients with chronic rhinosinusitis who were
      submitted to endoscopic sinus surgery. AR was used to determine minimum nasal
      cross-sectional area and volume as the indices of the nasal patency in all
      patients on the day before the surgery and 3 months postoperatively. We did not
      find any significant alteration when comparing the pattern of fluctuation, the
      periodicity, and the amplitude of the nasal cycle demonstrated by patients in the
      pre and postoperative periods, confirming that this surgery does not have any
      adverse effect on this physiologic cycle.

PMID- 11453503
TI  - Chronic rhinosinusitis: is the nose really involved?
AB  - To determine whether chronic rhinitis usually accompanies chronic sinusitis, and
      critically examine the concept of chronic rhinosinusitis, paired specimens of
      nasal septal mucosa and ethmoid sinus mucosa were obtained in a prospective
      cohort of 42 patients undergoing endoscopic sinus surgery for chronic
      rhinosinusitis. The histopathological degree of inflammation for each specimen
      was scored using a five-point rating scale. Cell counts for eosinophils and
      inflammatory cells per high-power field (HPF) were determined. Mean patient age
      was 40.5 years and mean Lund score was 9.3. The inflammation grade of the septal
      mucosa was within one point of the ethmoid mucosa in 36 (85.7%) cases, and
      correlated exactly in 24 patients (57.1%). A statistically significant
      correlation was found between septal and ethmoid mucosa inflammation grades (p =
      0.048). No significant difference in mean non-eosinophilic inflammatory cell
      count per HPF was noted betmeen ethmoid mucosa and septal mucosa (48.2 versus
      54.3 cells/HPF, p = 0.061, power = 0.873). Ethmoid mucosa had a significantly
      higher mean eosinophil count than septal mucosa (6.6 versus 1.9 cells/HPF, p <
      0.001). For combined inflammatoty cell counts, no significant difference in cell
      counts was noted (54. 7 cells/HPF ethmoid versus 56.1 septal, p = 0.670, power =
      0.847). Histopathologic evidence of rhinitis is associated with chronic
      sinusitis. This supports the concept of rhinosinusitis rather than sinusitis
      alone. Eosinophils are found in significantly higher numbers in sinus mucosa than
      in nasal mucosa, suggesting a site-specific role in rhinosinusitis.

PMID- 11453504
TI  - Production of beta-defensin antimicrobial peptides by maxillary sinus mucosa.
AB  - beta-Defensins are endogenous cationic peptides with broad-spectrum antimicrobial
      activity that are thought to play a role in the innate immune response. Two human
      beta-defensins, beta-defensin-1 (HBD-1) and beta-defensin-2 (HBD-2), have been
      identified. These peptides have recently been characterized in several human
      tissues. The presence of these peptides in the paranasal sinuses has not been
      investigated. We examined maxillaary sinus secretions from six patients with
      sinusitis and 10 patients without signs, symptoms, or radiologic evidence of
      sinus disease for the presence of beta-defensins. Cationic peptides were
      extracted from antral lavage specimens and examined for the presence of HBD-1 and
      HBD-2 by Western blot. Normal maxillary sinus epithelium was obtained from two
      patients and analyzed by RT-PCR for the presence of HBD-1 and HBD-2 mRNA. Tissue
      immunostaining for the two peptides was also used. Western blot analysis
      identified HBD-1 in two of 10 patients in the control group and in three of six
      patients in the sinusitis group. HBD-2 was identified in one of 10 patients in
      the control group and in four of six patients in the sinusitis group. RT-PCR
      revealed HBD-1 mRNA in one of two normal controls tested. Immunostaining
      localized HBD-1 and HBD-2 to the epithelial cell cytoplasm. This is the first
      demonstration of HBD-1 and HBD-2 production in the paranasal sinuses. In the
      present study, HBD-1 and HBD-2 were detected more frequently in the maxillary
      sinus fluid of patients with inflamed sinuses than in normal controls.

PMID- 11453505
TI  - Chronic sinusitis complicating sinus lift surgery.
AB  - Sinusitis has been reported as a complication of sinus lift surgery with antral
      bone augmentation. The procedure involves the creation of a submucoperiosteal
      pocket in the floor of the maxillary sinus for placement of a graft consisting of
      autogenous, allogenic, or alloplastic material. This can result in inadvertent
      tearing of the mucoperiosteal flap with extrusion of graft material into the
      antrum. Obstruction of the sinus outflow tract by mucosal edema and particulate
      graft material may result in sinusitis. We will discuss the clinical presentation
      and management of 14 cases of chronic sinusitis following sinus lift surgery with
      alloplastic hydroxyapatite (HA) augmentation of the maxillary antrum.

PMID- 11453506
TI  - The potency of culture-expanded nasal septum chondrocytes for tissue engineering
      of cartilage.
AB  - Tissue engineering techniques to create extra autologous cartilage for
      reconstructive surgery receive more and more scientific and industrial attention.
      The objective of this experimental study was to assess the use of in vitro
      multiplied chondrocytes of the nasal septum for generation of cartilage grafts
      using tissue engineering techniques. Cells isolated from a biopsy of septal
      cartilage of rabbits and humans were expanded in culture to get a sufficient
      number of cells to engineer a cartilage graft. The drawback of the expansion
      procedure is that the cells lose their cartilaginous phenotype
      (dedifferentiation). We studied a method to reverse the dedifferentiation of
      expanded cells to stimulate them to produce cartilage matrix of good quality.
      Rabbit chondrocytes showed reversion of dedifferentiation (redifferentiation)
      when fetal calf serum was replaced by the growth factors IGF1 and TGFbeta2. This
      was expressed by increased glycosaminoglycan synthesis and increased numbers of
      collagen type II-producing cells. The redifferentiation capacity of septal
      cartilage cells of young rabbits was higher than that of adult rabbits. In human
      chondrocytes from the nasal septum redifferentiation could also be induced by
      replacement of serum with IGF1 and TGFbeta2. This method, however, was less
      efficient than in rabbits. Chondrocytes of older patients (>40 years old) were no
      longer sensitive to the growth factor treatment. In conclusion, our study
      demonstrates a method to regain cartilage phenotype in multiplied cells of nasal
      septum cartilage needed for tissue engineering of new cartilage. These results
      are promising for this technique to generate cartilage grafts for facial plastic
      surgery of the nasal septum.

PMID- 11453507
TI  - Histopathologic evaluation of the ethmoid bone in chronic sinusitis.
AB  - Chronic rhinosinusitis (CRS) is defined as a condition lasting for a period
      greater than 12 weeks, and manifested by an inflammatory response involving the
      mucous membranes of the nasal cavity and paranasal sinuses, fluids within these
      cavities, and/or the underlying bone. The mucosal changes that occur in CRS have
      been well described, and include edema, decreased number of ciliated cells, and
      goblet cell hyperplasia. However, the changes that may occur in the underlying
      ethmoid bone have only recently been investigated. We evaluated decalcified
      ethmoid bone specimens from 20 patients undergoing endoscopic sinus surgery for
      CRS. Our analysis revealed histopathologic changes consistent with varying grades
      of bone remodeling. Polarized light microscopy demonstrated changes in the
      extracellular matrix, such as bone resorption and neoosteogenesis. Preoperative
      clinical data and CT staging were recorded on all patients and correlated with
      the histopathologic findings. These findings suggest that CRS may be associated
      with osteitis of the underlying ethmoid bone.

PMID- 11453508
TI  - Histomorphometric analysis of human sphenoid and maxillary mucosa: measurement of
      relative density of goblet cells and basal cells.
AB  - The majority of malignant tumors of the paranasal sinus are squamous cell
      carcinomas and arise most commonly in the maxillary sinus, and less commonly in
      the nasal cavity and other sinuses. Glandular tumors (nonsquamous tumors) develop
      much less commonly and have a different distribution within the paranasal
      sinuses. The majority of adenomatous tumors arise from the surface mucosa and
      submucosal seromucinous glands. Attempts to explain tumorigenesis propose that
      the distribution of these tumors is based on the variance of different cell types
      among the sinuses. The authors used morphometric analysis to measure the relative
      density of goblet cells and basal cells from maxillary, and sphenoid sinus
      specimens. Surgical specimens of normal maxillary and sphenoid mucosa were
      retrieved from 5 and 10 patients, respectively. All specimens were stained with
      periodic acid-Schiff stain. The area of goblet and basal cells in five
      representative areas of each specimen were measured and compared to the total
      cross-sectional area of the mucosa, giving a relative density of each cell type.
      The average goblet cell density was 31.19% (SD +/- 10.27%) in maxillary tissue
      and 33.25% (SD +/- 20.80%) in sphenoid tissue. Student's t-test showed no
      statistically significant difference in goblet cell density between the two
      sinuses. The average basal cell density was 9.53% (SD +/- 0.87%) for maxillary
      tissue and 10.91% (SD +/- 1.91%) for sphenoid tissue. Again, no statistically
      significant difference between the two sinuses existed. In conclusion, there is
      no clearly detectable difference in the histologic composition of these two
      paranasal sinuses to explain the different incidence of glandular tumors, and
      other etiologic factors must be considered in explaining tumorigenesis at these
      sites.

PMID- 11453509
TI  - Ipratropium bromide nasal spray for treatment of rhinorrhea in the
      laryngectomized patient: a pilot study.
AB  - Many who have had a total laryngectomy complain of unrelenting rhinorrhea that is
      often very difficult to control. This study was undertaken to evaluate the effect
      of ipratropium bromide (IB), an anticholinergic nasal spray, on rhinorrhea in
      these patients. This was designed as a prospective, randomized, double-blind,
      placebo-controlled, crossover pilot study. Participants were selected if they had
      a total laryngectomy and complained of rhinorrhea. They were asked to rate the
      severity and duration of their rhinorrhea each day throughout the study on a
      scale from zero to six. Each participant was initially given a saline nasal spray
      for one week. They were then randomized to use either IB or saline for the double
      blinded portion of the study. Two sprays of IB at a dose of 42 micrograms/spray
      (0.06%), or saline, were administered intranasally twice daily for two weeks,
      after which time the participants were given another nasal spray (either IB or
      saline) for the crossover portion of the study. Six patients entered and
      completed the study. Those patients using the IB recorded a mean 55% decline in
      severity and a mean 51% decline in duration of the rhinorrhea as compared to
      placebo. The relief in both severity and duration of rhinorrhea obtained by
      patients was analyzed using the Wilcoxon signed-rank test and found to be highly
      significant (p < 0.001). Despite the limitations of a small sample size in this
      study, ipratropium bromide nasal spray significantly reduced both the severity
      and duration of rhinorrhea in laryngectomized patients. We suggest ipratropium
      nasal spray as a safe, effective way to treat chronic rhinorrhea in
      laryngectomized patients, improving their quality of life.

PMID- 11453510
TI  - Extent of pathological changes in the paranasal sinuses of patients with cystic
      fibrosis: CT analysis.
AB  - The aim of the study was to define the characteristic changes revealed by
      computed tomography (CT) examination of the paranasal sinuses in patients with
      cystic fibrosis (CF). The group of 30 CF patients was evaluated in the outpatient
      clinic of the Department of Otorhinolaryngology, Medical University of Warsaw,
      from 1996 to 1998. The control group consisted of 30 patients with chronic
      rhinosinusitis (CRS). CT scans were obtained from both groups of patients, and
      findings revealed more advanced pathological changes in the CF than CRS group.
      The extensive inflammatory process observed in CT scans of CF patients resulted
      in the impairment of frontal and maxillary sinus development, destruction of bony
      structures, and medial projection of the lateral nasal wall.

PMID- 11453511
TI  - Sinonasal disease in patients with sarcoidosis.
AB  - Sarcoidosis is a chronic granulomatous disease of unclear etiology with a
      propensity to involve the lower respiratory tract, but may also involve the upper
      respiratory tract. Histologically, it is characterized by non-caseating
      granulomas of various organ systems. Although nasal and sinus involvement is
      uncommon, patients with sarcoidosis presenting with nasal and sinus complaints
      may have sinonasal sarcoidosis or simply rhinosinusitis. We reviewed the cases of
      six patients with pulmonary sarcoidosis who developed chronic sinonasal disease.
      All six patients had intranasal findings consistent with sinonasal sarcoidosis,
      but only four had histologic evidence of sinonasal sarcoidosis. These four
      patients continue to require extensive therapy including topical steroids,
      systemic steroids, intralesional steroid injections, and nasal irrigations. We
      conclude that patients with histologically proven sinonasal sarcoidosis present a
      significant therapeutic challenge because their symptoms and physical findings
      are often persistent despite aggressive medical and surgical therapy. Their
      recalcitrant sinonasal disease is thought to result from the destruction of cilia
      and mucus-producing glands by the granulomatous process.

PMID- 11453512
TI  - The story of Lot and the Qur'an's perception of the mortality of same-sex
      sexuality.
AB  - Discussion of the morality of same-sex sexuality in Islam is beginning to come to
      the forefront. It is a controversial topic that evokes differing views in Islam
      and, as such, needs to be addressed and understood. This study narrows the scope
      of the investigation to the use of moral terminology in the Lot story and
      elsewhere in the Qur'an. The method of semantic analysis that shall be applied is
      similar to the one espoused by Toshihiko Izutsu. In order to acquire a better
      understanding of how same-sex practices are qualified morally in the Qur'an, same
      sex activities shall also be looked at in comparison to other opposite-sex and
      non-sexual practices. It is my contention that, in the Qur'an, same-sex practices
      are viewed no differently from certain opposite-sex and non-sexual activities. In
      quoting from the Qur'an, I will give my own translation of the Arabic terms that
      shall be analyzed. In general, however, I adopt Qur'anic passages from Arthur J.
      Arberry, The Koran Interpreted, and where necessary, modify Qur'anic passages
      with my own translations. I will also use Arberry's verse numbering, following
      that of Flugel.

PMID- 11453513
TI  - The Pentagon's gay ban is not based on military necessity.
AB  - When President Bill Clinton attempted to lift the U.S. military's ban on gay and
      lesbian soldiers, Congress reacted by enacting a law that prohibits known
      homosexuals from serving in the U.S. armed forces. The official justification for
      the new policy is the unit cohesion rationale, the notion that if known gays and
      lesbians were allowed to serve, unit cohesion, performance, readiness and morale
      would decline. The thesis of this paper is that the evidence that advocates of
      discrimination invoke to support the plausibility of the unit cohesion rationale
      does not constitute scientifically valid data. This paper was delivered
      originally as a lecture at the Commonwealth Club of California and broadcast
      subsequently on National Public Radio.

PMID- 11453514
TI  - Sexual orientation beliefs: their relationship to anti-gay attitudes and
      biological determinist arguments.
AB  - Previous studies which have measured beliefs about sexual orientation with either
      a single item, or a one-dimensional scale are discussed. In the present study
      beliefs were observed to vary along two dimensions: the "immutability" of sexual
      orientation and the "fundamentality" of a categorization of persons as
      heterosexuals and homosexuals. While conceptually related, these two dimensions
      were empirically distinct on several counts. They were negatively correlated with
      each other. Condemning attitudes toward lesbians and gay men were correlated
      positively with fundamentality but negatively with immutability. Immutability,
      but not fundamentality, affected the assimilation of a biological determinist
      argument. The relationship between sexual orientation beliefs and anti-gay
      prejudice is discussed and suggestions for empirical studies of sexual
      orientation beliefs are presented.

PMID- 11453515
TI  - Student attitudes toward lesbian, gay, and bisexual issues: analysis of self-talk
      categories.
AB  - The purpose of this study was to (a) examine the utility of using the thought
      listing technique to examine participants' attitudes toward lesbian, gay, and
      bisexual issues and (b) determine the effectiveness of two new training
      interventions (rational and experiential) that were designed using cognitive
      experiential self-theory (Epstein, 1994). Fifty participants were randomly
      assigned to one of three treatment conditions (rational training, experiential
      training, control group). Participants completed a thought-listing technique
      before and after receiving one of the theoretically based training interventions.
      Three judges free sorted the 2,481 collected thoughts and identified and defined
      25 thought categories. Three trained judges then placed 2,426 (98%) of the
      thoughts into these categories. Results indicated that different categories of
      responses (cognitive, affective, behavioral) emerged among the individuals which
      provided four distinct profiles of how people thought about the topic of
      homosexuality. Furthermore, chi-square analyses revealed that the experiential
      group had changes in their thoughts after receiving the workshop. Findings are
      discussed and suggestions for future research are provided.

PMID- 11453516
TI  - Heterosexual identity and heterosexism: recognizing privilege to reduce
      prejudice.
AB  - We propose that heterosexuals' attitudes toward their own heterosexual identity
      evolve in a manner similar to the development of racial identity attitudes among
      Whites-another dominant group with privileged social status. A more developed
      heterosexual identity, we hypothesized, would be associated with diminished
      levels of negative attitudes toward non-heterosexuals. To test our hypotheses, we
      administered to 154 heterosexual students Herek's (1988) Attitudes Toward Gays
      and Lesbians scale measuring heterosexist (i.e., anti-gay) attitudes and a
      version of Helms and Carter's (1990) White Racial Identity Attitude Scale (WRIAS)
      modified to assess heterosexual identity attitudes. Hierarchical regression
      analyses controlling demographic indicators partially confirmed the hypothesized
      associations between evolving identity stages and less heterosexist attitudes.
      The role of recognizing one's social privilege is proposed (though not
      empirically examined) as a potential mediator between developing a dominant group
      identity and decreasing prejudicial attitudes towards non-privileged groups.
      Finally, implications and recommendations for future research and addressing
      heterosexism are presented.

PMID- 11453517
TI  - Glory holes and the men who use them.
AB  - This paper gives a brief description of the "glory hole" and its popularity in
      certain arenas of public homosexual activity along with an overview of academic
      and underground resources that have acknowledged its existence. Testimonies,
      drawn from interviews with ten openly homosexual men in San Francisco who have
      used glory holes for sexual encounters with varying frequency, form the bulk of
      the paper, testifying to the diverse motivations, experiences and perceptions
      that make the glory hole appealing to its users.

PMID- 11453518
TI  - Short normal stature and psychosocial disadvantage: a critical review of the
      evidence.
AB  - Physicians and parents alike are under increasing pressure to identify and to
      treat short stature, but intervention implies the presence of some pathology,
      physical or psychological, that can be corrected. Where there is true GH
      deficiency, the argument for replacement is uncontroversial. It is less
      compelling where GH 'insufficiency' is diagnosed. In the case of the short, but
      otherwise normal, child the indications for therapy are even less clear. Short
      stature, per se, is clearly not a disease, in spite of the perception by some
      practitioners that the rate of growth of such children is abnormal. Short stature
      is, however, commonly perceived to be associated with social and psychological
      disadvantage, yet many of these misperceptions about short stature can be
      challenged. A critical review of the literature pertaining to the psychosocial
      correlates of short stature uncovers much flawed evidence. Most importantly, the
      belief, widely held by paediatricians, that short children are likely to be
      significantly disadvantaged, has been founded largely on data from clinic
      referred samples. In such studies, children with real (or perceived) behavioural
      or academic problems are likely to be overly represented. Publications arising
      from such studies, however, inevitably lead to an increase in the demand for
      treatment both from and for those who previously had no such concern. In
      contrast, data from a well controlled, prospective population-based study suggest
      the essential normality of the short normal child. Parents and children alike
      should be reassured by these findings. In the absence of clear pathology,
      physical or psychological, GH therapy for short but otherwise normal children
      must therefore, in most cases, be deemed cosmetic, raising issues as to the
      ethics of so-called "plastic endocrinology".

PMID- 11453519
TI  - Feminizing genitoplasty in patients with 46XX congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is the most common cause of ambiguous
      genitalia in newborns. This paper is based upon review of the literature and
      personal experience. We focus upon the surgical anatomy, pre-operative
      evaluation, including imaging, mainly by transabdominal ultrasound, and upon the
      goals and the history of surgical reconstruction. The various surgical techniques
      are mentioned with a detailed description of our technique used in 52 patients.
      The timing and staging of the operation and the implications of prenatal therapy
      are discussed. In conclusion, we believe that infants with 46XX CAH can undergo
      one-stage feminizing genitoplasty very early in life with satisfactory cosmetic
      and functional results.

PMID- 11453520
TI  - The complexity of body composition evaluation in children and adolescents.

PMID- 11453521
TI  - The anabolic steroid oxandrolone increases muscle mass in prepubertal boys with
      constitutional delay of growth.
AB  - The aim of this study was to investigate the effect of oxandrolone on body
      composition in boys with constitutional delay of growth and puberty. In 14
      prepubertal boys, height, weight, triceps and subscapular skinfolds and upper arm
      circumference were measured. Body mass index, the ratio of subscapular to triceps
      skinfolds and the upper muscle area were also determined. The difference of the
      various measurements and indices, 3 to 6 months before and after commencement of
      oxandrolone treatment, were calculated, while the boys remained prepubertal. We
      observed a marked increase in body mass index, a decrease of triceps and
      subscapular skinfolds, an increase in the ratio of subscapular to triceps
      skinfolds and also an increase in upper muscle area after the onset of
      oxandrolone treatment. These results suggest that low dose oxandrolone
      administration in prepubertal boys with constitutional growth delay causes a
      disproportionate increase of weight to height which is largely due to increased
      body muscle.

PMID- 11453522
TI  - Can GnRH-agonist treatment cause slipped capital femoral epiphysis?
AB  - Slipped capital femoral epiphysis (SCFE) mainly occurs in pubertal children and
      is associated with delayed skeletal maturation, obesity, high growth velocity and
      tall stature. Furthermore, SCFE often coincides with endocrine disorders. This is
      the first report of a possible relationship between SCFE and GnRH agonist
      treatment: four patients developed SCFE during or shortly after treatment with
      GnRH agonists was stopped. We compared the clinical aspects of these patients
      with patients described in the literature who developed SCFE. Puberty started at
      the age of 3.3, 9.6, 0.0 and 5.6 years respectively. One patient developed
      sequential SCFE of both hips. SCFE occurred at the age of 11.9 (patient 1), 12.7
      (patient 2), 14.3 (patient 2), 11.3 (patient 3) and 11.3 (patient 4) years. Of
      the five incidences of SCFE, one occurred during GnRH agonist treatment and four
      shortly after treatment was stopped. None of our patients met the typical
      criteria seen in SCFE and no 'regular' characteristics of patients with SCFE
      could be designated. Probably the hormonal changes during and shortly after
      treatment with GnRH agonists make the epiphysis more prone to slip. Considering
      our observations and by reviewing the literature, GnRH agonist treatment might
      present a risk factor for the occurrence of SCFE.

PMID- 11453523
TI  - An open-label acceptability study of Norditropin SimpleXx--a new liquid growth
      hormone formulation.
AB  - A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to
      avoid the need for reconstitution before administration. In addition, the liquid
      GH formulation has been combined with an advanced pen delivery system, either
      with or without a needle auto-insertion mechanism. This study was designed to
      assess the acceptability of the new system compared with the patient's previous
      system. A total of 103 children with GH deficiency received a daily injection of
      Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system.
      Acceptability was determined by nurse-supervised questionnaires administered to
      the patients and parents. Following treatment, 94% of patients preferred the
      Norditropin liquid GH system. This preference was irrespective of the previous
      system in use, patient age or length of GH therapy. More patients found it the
      less painful system (50% vs 13%), 92% of patients found it more convenient, and
      the formulation was well tolerated. In conclusion, Norditropin liquid GH was very
      well accepted and preferred by the majority of patients. It avoided
      reconstitution which had been a major cause of dissatisfaction with the patients'
      previous systems, and resulted in greater convenience and reduced levels of pain
      associated with injection.

PMID- 11453524
TI  - Serum levels of cytokines in children and adolescents with Graves' disease and
      non-toxic nodular goiter.
AB  - It has been shown that human thyrocytes can synthesize cytokines which activate T
      and B lymphocytes. These immune cells play important roles in the initiation and
      continuation of thyroid autoimmunity. The aim of this study was to estimate serum
      concentrations of soluble interleukin-6 receptor (sIL-6R), interleukin-6 (IL-6)
      and interleukin-8 (IL-8) in patients with Graves' disease (GD) (n=44, mean age
      14.8 years), in patients with nontoxic nodular goiter (NTNG) (n=36, mean age 15.6
      years) and in a group of healthy controls (n=20, mean age 14.5 years). ELISA was
      used to determine the concentration of cytokines, antithyroglobulin and
      antithyroid peroxidase antibodies in patients with thyroid disease. Radio
      receptor assay (RRA) was performed to detect anti-TSH receptor autoantibodies
      (TRAb). Serum levels of IL-6, sIL-6R and IL-8 were markedly elevated in patients
      with GD before treatment with methimazole (p<0.0001 for IL-6, p<0.006 for sIL-6R,
      p<0.004 for IL-8) and after 8 weeks of therapy (p<0.011 for IL-6, p<0.04 for IL
      8). However, following 24 months of treatment, normal serum concentrations of
      these cytokines were restored. Furthermore, patients with NTNG showed a slightly
      elevated concentration of cytokines (IL-6, IL-8). Serum levels of tri
      iodothyronine in patients with GD positively correlated with serum concentrations
      of IL-6 (r = 0.35, p<0.025) and sIL-6R (r = 0.31, p<0.047), while no correlation
      was found between thyroxine and cytokines. Moreover, we observed a positive
      correlation between serum levels of TPO-Abs, TRAb and IL-6 (r = 0.43, p<0.008; r
      = 0.5, p<0.003) and between TPO-Abs and IL-8 (r = 0.67, p<0.0001). However, in
      patients with NTNG no correlation was observed between serum levels of
      antithyroid antibodies or thyroid hormones and serum levels of cytokines. We
      conclude that the cytokines (IL-6, sIL-6R, IL-8) could play an important role in
      the development of Graves' disease and that their levels are modulated by
      thyreostatic treatment.

PMID- 11453525
TI  - Multinodular goiter in children.
AB  - OBJECTIVE: As multinodular goiter (MNG) is an uncommon pediatric disorder, we
      decided to evaluate the children with this diagnosis at our center to try to
      delineate better its etiology, the risk of malignancy and appropriate management
      strategies. METHODS AND RESULTS: Eighteen patients (12 girls and 6 boys) were the
      subject of this retrospective review spanning a period of 20 years. All were
      previously well, except one, and none had had head or neck irradiation. Average
      age at diagnosis was 12.8 years. Four children belonged to two previously
      identified kindreds diagnosed with familial MNG. These families had members
      affected with multiple cases of non-medullary thyroid carcinoma (NMTC). All were
      euthyroid and had no symptoms. In eight of 18 patients, the clinical examination
      missed the presence of multiple nodules which were subsequently detected by
      ultrasound. Twelve patients had tissue diagnosis by fine needle aspirate cytology
      (FNAC) or surgery. Five of eight patients undergoing surgery had nodular
      hyperplasia, one had a follicular adenoma and one had a normal thyroid gland on
      histology. There was one patient with papillary carcinoma combined with nodular
      hyperplasia. Seven of the patients had evidence of antithyroid autoimmunity.
      CONCLUSION: The etiology of pediatric MNG appears multifactorial including
      autoimmune and familial factors. We believe that previously healthy children can
      usually be managed conservatively. Ultrasound at the time of diagnosis and in
      follow up seems beneficial. Familial forms appear to warrant close follow up,
      given the apparent increased risk of malignancy. The risk of malignancy while low
      remains real.

PMID- 11453526
TI  - Critical growth phases for adult shortness in Hong Kong Chinese.
AB  - OBJECTIVES: This study was designed to explore whether the influence of subnormal
      growth in fetal, infancy, childhood and pubertal phases on adult short stature
      was the same when comparing privileged and underprivileged populations. METHODS:
      Data came from two longitudinal growth studies: 1) Hong Kong Chinese children who
      were born in 1967 (n = 132), and 2) the comparatively more privileged Swedish
      children who were born in 1973-1975 (n = 2,850). RESULTS: 68% of Hong Kong
      Chinese children had two or more growth phases subnormal, much higher than the
      12.4% for Swedish children. 42.4% of Hong Kong Chinese were short at final
      height, much higher than the 2.2% for Swedish children. Subnormal growth in any
      growth phase was associated with an increased risk of adult short stature in both
      series (p<0.01). After adjustment for mid-parental height, the place of residence
      (Hong Kong/Sweden) was not significant for adult shortness (p>0.05) in the pooled
      data. CONCLUSIONS: The impact of subnormal growth in any phase on adult shortness
      is similar in privileged and underprivileged populations. The much higher
      prevalence of subnormal growth and consequently adult short stature in developing
      countries is likely mainly attributable to adverse extrinsic or environmental
      influences.

PMID- 11453527
TI  - Prevalence of ICA and GAD antibodies at initial presentation of type 1 diabetes
      mellitus in Singapore children.
AB  - OBJECTIVE: To determine the prevalence of islet cell antibodies (ICA) and
      antibodies to glutamic acid decarboxylase (GAD) in Asian children with diabetes
      mellitus (DM) at the time of diagnosis. PATIENTS AND METHODS: 41 children were
      studied at their initial presentation from 1993 to 2000. RESULTS: Mean age of
      onset (+/- SD) of DM was 7.6 (+/- 4.2) years. One or both of the two
      autoantibodies, ICA and anti-GAD, were present in 17 of the 41 children (41.5%)
      at the time of diagnosis. Comparing the group of children with autoantibodies and
      the group without detectable autoantibodies, there were no significant
      differences in body mass index (15.4 vs. 16.3 kg/m2), age of onset (7.4 vs. 7.8
      years), random C-peptide levels (203 vs. 311 pmol/l), HbA1c levels (13.2 vs.
      12.7%), and frequency of diabetic ketoacidosis at presentation (53.3 vs. 55%).
      CONCLUSION: Prevalence of antibodies at presentation of DM in Singapore (41.5%)
      is lower than in Caucasian populations (60-90%). Other autoantibodies yet to be
      identified may be contributory. Alternatively, non-immune mediated mechanisms may
      be responsible for a significant proportion of type 1 DM in Singapore children.

PMID- 11453528
TI  - Study of zinc and growth hormone in sickle cell disease.
AB  - About 25% of children with sickle cell disease (SCD) have statural deficit and
      retarded skeletal maturation and pubertal development. These disorders have been
      attributed to low serum concentrations of zinc. We report the study of serum zinc
      in 34 patients with SCD, of whom 17 had statural deficit (SCS group) and 17
      without growth deficiency (SCN group). They were compared with 20 normal children
      (N group). GH secretion and thyroid function were investigated in the group with
      short stature (SCS) in order to rule out GH deficiency and hypothyroidism. The
      mean serum zinc concentration was 108.45+/-22.888 microg/100 ml in the N group,
      87.529+/-30.069 microg/100 ml in the SCN group and 82.765+/-34.766 microg/100 ml
      in the SCS group. There was a statistically significant difference between the
      mean of the N group and the mean of the SCN group (p<0.05) but no difference was
      found between the two groups of patients (N>SCN=SCS). Although there is a well
      established zinc deficiency in patients with SCD, the statural retardation found
      in the SCS group could not be attributed only to zinc deficiency. Many other
      severe metabolic disturbances are also involved.

PMID- 11453529
TI  - Seasonality of birth in children (0-14 years) and young adults (0-29 years) with
      type 1 diabetes mellitus in Sardinia differs from that in the general population.
      The Sardinian Collaborative Group for Epidemiology of IDDM.
AB  - A cohort of 1,118 children (0-14 years) and 810 adolescents and young adults (15
      29 years) with type 1 diabetes mellitus (DM) diagnosed in Sardinia between 1989
      and 1998 were analyzed for seasonality of month of birth, and compared to the
      pattern registered in 314,084 live births. Patients with DM of both age groups
      had a statistically significant different seasonality pattern from the general
      population, revealing an increased birth rate during the summer months, a mirror
      image of the seasonality of onset of disease.

PMID- 11453530
TI  - Prolonged hypocalcemia in a 2 month-old boy unmasking maternal diagnosis of
      primary hyperparathyroidism.

PMID- 11453531
TI  - Gonadotropin releasing hormone-independent precocious puberty in a 5 year-old
      girl with suprasellar germ cell tumor secreting beta-hCG and alpha-fetoprotein.
AB  - A 5 year-old girl presented with typical features of isosexual precocity with
      breast and pubic hair development (Tanner stage 3) and menarche, following a few
      months history of hirsutism of the back and thighs. Stimulation testing revealed
      GnRH-independent precocious puberty, tertiary hypothyroidism, hyperprolactinemia
      and mild testosteronemia. The ovaries in ultrasound examination were prepubertal.
      Tumor markers beta-hCG and AFP were markedly elevated and a 2.5 x 1.5 cm
      suprasellar germ cell tumor (GCT) was visualized by MRI. Combined chemotherapy
      followed by radiotherapy resulted in normalization of pubertal features along
      with estrogen and marker levels. Our observations support the possibility of hCG
      dependent precocious puberty (PP) in girls caused by suprasellar hCG-secreting
      tumor. We emphasize the need of diagnostic management of hCG-dependent PP not
      only in boys, but also in girls, especially when they present even slight
      features of androgenization. We hypothesize that the rarity of isosexual PP in
      girls with hCG-secreting suprasellar GCT results not only from the lower
      occurrence of these tumors in girls than in boys, but above all from a rare
      simultaneous concomitant incidence of both high tumor aromatase activity and hCG
      secreting potency.

PMID- 11453532
TI  - 47,XYY karyotype and normal SRY in a patient with a female phenotype.
AB  - A rare case of a female patient with a 47,XYY karyotype is described. She had
      normal female external genitalia, bilateral testes, rudimentary Fallopian tubes
      and no uterus. Molecular analysis revealed a normal SRY encoding sequence. The
      possible events in the etiology of this sex reversal entity are discussed.

PMID- 11453533
TI  - Hypospadias in a patient with Kabuki make-up (Niikawa-Kuroki) syndrome.
AB  - A patient showing the typical facies and other signs of Kabuki make-up syndrome
      (KMS) was also found to have hypospadias, a finding previously reported only once
      in a patient with KMS.

PMID- 11453534
TI  - Cohen syndrome with acanthosis nigricans and insulin resistance.
AB  - Cohen syndrome is a rare genetic disorder consisting of truncal obesity,
      hypotonia, mental retardation, microcephalia, characteristic facial appearance
      and ocular anomalies. Other diagnostic clinical features include narrow hands and
      feet, low growth parameters, neutropenia and chorioretinal dystrophy. Acanthosis
      nigricans is a cutaneous disorder characterized by hyperpigmentation and
      papillomatosis. Syndromal acanthosis nigricans may occasionally appear as a
      feature of several specific syndromes. We report a patient showing the typical
      characteristics of Cohen syndrome with acanthosis nigricans and hyperinsulinemia.

PMID- 11453535
TI  - Cardiac twitch properties simulated by three-states model.
AB  - We examined whether the three states model can explain the systolic and
      relaxation properties of cardiac muscle to clarify what factors affect these
      properties. Changing the values of the parameters describing the calcium
      transient and calcium sensitivity, we estimated the effects of these parameters
      on the systolic and relaxation properties of twitch contraction. The simulations
      showed the following four features: 1) An increase in the maximum calcium
      concentration and calcium sensitivity, and a prolongation of the calcium
      transient led to an increase in peak tension associated with an increase in the
      time to peak tension. 2) An increase in myosin ATPase activity led to an increase
      in peak tension associated with a decrease in the time to peak tension. 3) An
      increase of peak tension was accompanied by a prolongation of the late systolic
      period. 4) The constant of the late tension relaxation from 25% to 10% of the
      peak tension was altered when the crossbridge cycling rate, the resting calcium
      concentration or the late decline of the calcium transient was changed. The
      simulation were not contradictory to the experimental results and showed that
      three state muscle model can provide qualitative descriptions on the systolic and
      relaxation characteristics of cardiac muscle.

PMID- 11453536
TI  - A novel approach to ex vivo gene therapy for familial hypercholesterolemia using
      human amniotic epithelial cells as a transgene carrier.
AB  - This study has demonstrated the potential of human amniotic epithelial cells
      (HAEC) as a transgene carrier to treat patients with familial
      hypercholesterolemia (FH). One approach to liver-directed gene therapy is
      represented by transplantation of autologous hepatocytes that have been
      genetically modified in vitro. However, the hepatocytes must be isolated from
      surgically resected tissue and it is difficult to expand the hepatocytes in
      culture. In contrast, the advantages for using HAEC are the higher availability
      and the nonimmunogenicity after allotransplantation. Our strategy involved
      isolating HAEC from an amnion, transducing a human low-density lipoprotein
      receptor (LDLR) gene into these cells with a recombinant adenovirus, and
      transplanting the genetically modified cells into the liver of an animal model of
      FH. Each animal, treated with the LDLR-transduced HAEC, exhibited a substantial
      decrease in serum cholesterol with an eventual return to pretreatment level.
      Moreover, the transplanted HAEC migrated out of the sinusoids into the hepatic
      parenchyma and expressed the LDLRs until at least 20 days after transplantation.
      However, the transplanted HAEC markedly decreased in number after 10 days post
      transplant with an increase of inflammatory cells. The temporary nature of the
      metabolic improvement may be associated with xenograft rejection and transient
      function of the adenoviral vector.

PMID- 11453537
TI  - Normal tension glaucoma and primary open angle glaucoma associated with increased
      platelet aggregation.
AB  - On purpose of the present study was to evaluate platelet aggregation and
      fibrinolytic systems in patients with normal tension glaucoma (NTG) or primary
      open angle glaucoma (POAG). For platelet aggregation, we
      photoelectrophotometrically investigated adenosine diphosphate (ADP) or collagen
      induced platelet aggregation in consecutively selected patients with glaucoma (22
      patients with NTG and 13 patients with POAG) and 42 glaucoma free control
      subjects with normal ocular findings. The aggregation patterns of the patients'
      platelets reacted abnormally to ADP 1 microM or collagen 0.5 microg/ml as
      evidenced by secondary aggregation were compared with those of control subjects.
      For blood coagulative and fibrinolytic systems, we measured prothrombin time,
      activated partial thromboplastin time, fibrinogen, thrombin-antithrombin III
      complex (TAT), alpha2 plasmin inhibitor-plasmin complex. Seventeen of 22 patients
      (77%) with NTG and 5 of 13 patients (38%) with POAG showed abnormal secondary
      aggregation. A significant difference was observed between the two groups. No
      control subjects showed abnormal secondary aggregation. In the fibrinolytic test,
      all the parameters examined showed within normal ranges, although the log10(TAT)
      value was higher in NTG than in POAG. Results of the present study suggested that
      increased platelet aggregation as defined by ADP or collagen induced abnormal
      secondary aggregation in vitro is frequently associated with glaucoma patients
      and this tendency is more apparent in NTG than that in POAG.

PMID- 11453538
TI  - Effects of mechanical stimulation on gene expression of articular chondrocytes in
      polylayer culture.
AB  - Mechanical loads are constantly being applied to articular cartilage. However,
      comparatively few studies have investigated the effects of mechanical stress on
      the gene expression of chondrocytes. Hence, the objective of the present study
      was to clarify the effects of mechanical stress on cultured chondrocytes.
      Articular chondrocytes of rabbits were isolated and placed in minimun essential
      medium eagle a modification containing 10% fetal bovine serum. The chondrocytes
      were cultured in polylayer in polypropylene tubes. After 48 hours, centrifugal
      stress (2.7 MJ) was applied once every 24 hours for 28 consecutive days. The mRNA
      expression of insulin-like growth factor-I (IGF-I) and cartilage-specific genes
      (type II collagen and aggrecan) in chondrocytes, cell count, wet tissue mass and
      protein content were subsequently measured. The results showed that the mRNA
      expression of the IGF-I gene for the stress groups was significantly greater than
      that of the control group from days 3 to 5 of incubation, as was the mRNA
      expression of the type II collagen gene from days 7 to 14 of incubation. However,
      there were no significant differences in the mRNA expression of the aggrecan gene
      between the control and stress groups. The cell count for the stress groups was
      significantly higher from days 7 to 28 of incubation, and the wet tissue mass and
      protein content were significantly higher from days 14 to 28 of incubation. These
      findings suggest that one of the mechanisms by which mechanical stress increases
      the number of cultured chondrocytes and the volume of extracellular matrix is to
      increase IGF-I expression at the early stage of incubation.

PMID- 11453539
TI  - TGF-beta attenuates the transactivation activity of Ets-1 despite its induction
      via the inhibition of DNA binding.
AB  - We examined whether TGF-fl affects the transactivation activity of Ets-1. TGF
      beta augmented ets-1 mRNA expression and Ets-1 protein synthesis in ECV304 cells
      to the level equivalent to bFGF. When the DNA binding activity of Ets-1 protein
      was examined, bFGF was found to enhance DNA-Ets complex formation, whereas TGF
      beta attenuated basal as well as bFGF-enhanced DNA-Ets complex formation. As a
      result, TGF-beta attenuated the promoter activity driven by Ets-1. The DNA
      binding of Ets-1 protein was enhanced by the initial 4-hour bFGF treatment and
      the subsequent 8-hour cycloheximide treatment. When TGF-beta replaced
      cycloheximide in the subsequent 8-hour treatment, TGF-beta inhibited this bFGF
      enhanced DNA-Ets complex formation. When TGF-beta and cycloheximide were
      simultaneously added in the subsequent 8-hour treatment, the inhibitory effect of
      TGF-beta on bFGF-enhanced DNA-Ets complex formation was completely abolished.
      These results suggest the possibility that TGF-beta attenuates the
      transactivation activity of Ets-1 by inducing a protein that interferes with the
      binding of Ets-1 to the DNA binding site.

PMID- 11453540
TI  - Correlation between serum IL-6 levels and death: usefulness in diagnosis of
      "traumatic shock"?
AB  - Interleukin-6 (IL-6) has been considered as an important mediator of
      inflammation. Clinically it is a well-known marker of the severity of injury
      following major trauma. In this study, the levels of IL-6 in body serum were
      applied to a traumatic death index. Of ninety victims 55 were men and 35 women,
      with a mean age of 53.4+/- 19 (S.D.) years. The cases were classified as
      traumatic deaths (38 cases), non-traumatic deaths other than natural causes of
      deaths (36 cases), and deaths due to natural causes (16 cases). All samples were
      collected within 2 days after death. The mean values of IL-6 levels of the
      traumatic, non-traumatic and disease groups were 8608.97, 2205.65, and 3266.64
      pg/ml, respectively. Some cases in non-traumatic and disease cases were beyond 10
      000 pg/ml, however, the mean value of the traumatic group was statistically
      higher than that of the other two groups. Even though several cases had high
      levels of IL-6 in spite of instantaneous death, the results showed that IL-6
      levels are helpful in the diagnosis of traumatic shock.

PMID- 11453541
TI  - Bcl-2 over-expression and activation of protein kinase C suppress the trail
      induced apoptosis in Jurkat T cells.
AB  - Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel
      potent endogenous activator of the cell death pathway through the activation of
      cell surface death receptors Trail-R1 and Trail-R2. Its role, like FasL in
      activation-induced cell death (AICD), has been demonstrated in immune system.
      However the mechanism of Trail induced apoptosis remains unclear. In this report,
      the recombinant Trail protein was expressed and purified. The apoptosis-inducing
      activity and the regulation mechanism of recombinant Trail on Jurkat T cells were
      explored in vitro. Trypan blue exclusion assay demonstrated that the recombinant
      Trail protein actively killed Jurkat T cells in a dose-dependent manner. Trail
      induced apoptosis in Jurkat T cells were remarkably reduced by Bcl-2 over
      expression in Bcl-2 gene transfected cells. Treatment with PMA (phorbol 12
      myristate 13-acetate), a PKC activator, suppressed Trail-induced apoptosis in
      Jurkat T cells. The inhibition of apoptosis by PMA was abolished by pretreatment
      with Bis, a PKC inhibitor. Taken together, it was suggested that Bcl-2 over
      expression and PMA activated PKC actively down-regulated the Trail-mediated
      apoptosis in Jurkat T cell.

PMID- 11453542
TI  - Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin
      mediated cytotoxicity.
AB  - A major problem which is poorly understood in the management of bladder cancer is
      low sensitivity to chemotherapy and high recurrence after transurethral
      resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very
      important role in progression, invasion and metastasis of bladder cancer cells.
      In this study, we investigated whether IGF-1R was involved in the growth
      stimulating activity and drug resistance of bladder cancer cells. The results
      showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum
      free cultured T24 cell line, whereas normal urothelial cells did not express
      these factors/receptors or only in trace levels; T24 cell responded far better to
      growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R
      by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24
      cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC).
      These results suggested that blockage of IGF-IR signaling might potentially
      contribute to the treatment of bladder cancer cells which are insensitive to
      chemotherapy.

PMID- 11453543
TI  - Adenovirus-mediated expression of pig alpha(1, 3) galactosyltransferase
      reconstructs Gal alpha(1, 3) gal epitope on the surface of human tumor cells.
AB  - Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in
      large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the
      cells of lower mammalian animals such as pigs and mice. Human has no gal epitope
      due to the inactivation of alpha(1, 3) GT gene but produces a large amount of
      antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures
      specifically. In this study, a replication-deficient recombinant adenoviral
      vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and
      characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene
      into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901,
      and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal
      epitope did not increase the sensitivity of human tumor cells to human complement
      mediated lysis, although human complement activation and the binding of human IgG
      and IgM natural antibodies to human tumor cells were enhanced significantly after
      Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed
      the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA
      I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA),
      and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of
      gal epitope on the growth in vitro of human tumor cells was observed in MTT
      assay.

PMID- 11453544
TI  - Altered expression of nuclear matrix proteins in etoposide induced apoptosis in
      HL-60 cells.
AB  - The events of cell death and the expression of nuclear matrix protein (NMP) have
      been investigated in a promyelocytic leukemic cell line HL-60 induced with
      etoposide. By means of TUNEL assay, the nuclei displayed a characteristic
      morphology change, and the amount of apoptotic cells increased early and reached
      maximun about 39% after treatment with etoposide for 2 h. Nucleosomal DNA
      fragmentation was observed after treatment for 4 h. The morphological change of
      HL-60 cells, thus, occurred earlier than the appearance of DNA ladder. Total
      nuclear matrix proteins were analyzed by 2-dimensional gel electrophoresis.
      Differential expression of 59 nuclear matrix proteins was found in 4 h etoposide
      treated cells. Western blotting was then performed on three nuclear matrix
      acssociated proteins, PML, HSC70 and NuMA. The expression of the suppressor PML
      protein and heat shock protein HSC70 were significantly upregulated after
      etoposide treatment, while NuMA, a nuclear mitotic apparatus protein, was down
      regulated. These results demonstrate that significant biochemical alterations in
      nuclear matrix proteins take place during the apoptotic process.

PMID- 11453545
TI  - Maternal zinc deficiency impairs brain nestin expression in prenatal and
      postnatal mice.
AB  - Effects of maternal dietary zinc deficiency on prenatal and postnatal brain
      development were investigated in ICR strain mice. From d 1 of pregnancy (E0)
      until postnatal d 20 (P20), maternal mice were fed experimental diets that
      contained 1 mg Zn/kg/day (severe zinc deficient, SZD), 5 mg Zn/kg/day (marginal
      zinc deficient, MZD), 30 mg Zn/kg/day (zinc adequately supplied, ZA) or 100 mg
      Zn/kg/day (zinc supplemented, ZS and pair-fed, PF). Brains of offspring from
      these dietary groups were examined at various developmental stages for expression
      of nestin, an intermediate filament protein found in neural stem cells and young
      neurons. Immunocytochemistry showed nestin expression in neural tube 10.5 d post
      citrus (dpc) as well as in the cerebral cortex and neural tube from 10.5 dpc to
      postnatal d 10 (P10). Nestin immunoreactivities in both brain and neural tube of
      those zinc-supplemented control groups (ZA, ZS, PF) were stronger than those in
      zinc-deficient groups (SZD and MZD). Western blot analysis confirmed that nestin
      levels in pooled brain extracts from each of the zinc-supplemented groups (ZA,
      ZS, PF) were much higher than those from the zinc-deficient groups (SZD and MZD)
      from 10.5 dpc to P10. Immunostaining and Western blots showed no detectable
      nestin in any of the experimental and control group brains after P20. These
      observations of an association between maternal zinc deficiency and decreased
      nestin protein levels in brains of offspring suggest that zinc deficiency
      suppresses development of neural stem cells, an effect which may lead to
      neuroanatomical and behavioral abnormalities in adults.

PMID- 11453546
TI  - HAL1 mediate salt adaptation in Arabidopsis thaliana.
AB  - The yeast HAL1 gene was introduced into Arabidopsis thaliana by Agrobacterium
      tumefaciens-mediated transformation with vacuum infiltration under the control of
      CaMV 35S promoter. Thirty-three individual kanamycin resistant plants were
      obtained from 75,000 seeds. Southern blotting analysis indicated that HAL1 gene
      had been integrated into all of the transgenic plants' genomes. The copy number
      of HAL1 gene in transgenic plants was mostly 1 to 3 by Southern analysis.
      Phenotypes of transgenic plants have no differences with wild type plants.
      Several samples of transformants were self-pollinated, and progenies from
      transformed and non-transformed plants (controls) were evaluated for salt
      tolerance and gene expression. Measurement of concentrations of intracellular K+
      and Na+ showed that transgenic lines were able to retain less Na+ than that of
      the control under salt stress. Results from different tests indicated the
      expression of HAL1 gene promotes a higher level of salt tolerance in vivo in the
      transgenic Arabidopsis plants.

PMID- 11453547
TI  - Agrobacterium tumefaciens-mediated transformation of rice with the spider
      insecticidal gene conferring resistance to leaffolder and striped stem borer.
AB  - Immature embryos of rice varieties "Xiushuill" and "Chunjiang 11" precultured for
      4d were infected and transformed by Agrobacterium tumefaciens strain EHA101/pExT7
      (containing the spider insecticidal gene). The resistant calli were transferred
      onto the differentiation medium and plants were regenerated. The transformation
      frequency reached 56% approximately 72% measured as numbers of Geneticin (G418)
      resistant calli produced and 36% approximately 60% measured as numbers of
      transgenic plants regenerated, respectively. PCR and Southern blot analysis of
      transgenic plants confirmed that the T-DNA had been integrated into the rice
      genome. Insect bioassays using T1 transgenic plants indicated that the mortality
      of the leaffolder (Cnaphalocrasis medinalis) after 7d of leaf feeding reached 38%
      approximately 61% and the corrected mortality of the striped stem borer (Chilo
      suppressalis) after 7d of leaf feeding reached 16% approximately 75%. The insect
      bioassay results demonstrated that the transgenic plants expressing the spider
      insecticidal protein conferred enhanced resistance to these pests.

PMID- 11453548
TI  - Transgenic peanut plants obtained by particle bombardment via somatic
      embryogenesis regeneration system.
AB  - After pre-culture and treatment of osmosis, cotyledons of immature peanut
      (Arachis hypogaea L.) zygotic embryos were transformed via particle bombardment
      with a plasmid containing a chimeric hph gene conferring resistance to hygromycin
      and a chimeric intron-gus gene. Selection for hygromycin resistant calluses and
      somatic embryos was initiated at 10th d post-bombardment on medium containing 10
      25 mg/L hygromycin. Under continuous selection, hygromycin resistant plantlets
      were regenerated from somatic embryos and were recovered from nearly 1.6% of the
      bombarded cotyledons. The presence and integration of foreign DNA in regenerated
      hygromycin resistant plants was confirmed by PCR (polymerase chain reaction) for
      the intron-gus gene and by Southern hybridization of the hph gene. GUS enzyme
      activity was detected in leaflets from transgenic plants but not from control,
      non-transformed plants. The production of transgenic plants are mainly based on a
      newly improved somatic embryogenesis regeneration system developed by us.

PMID- 11453549
TI  - GABA transporter 1 transcriptional starting site exhibiting tissue specific
      difference.
AB  - GABA transporter 1(GAT1) takes important roles in multiple physiological
      processes through the uptake and release of GABA, but the regulation of GAT1 gene
      expression in different tissues is rarely known. To address the question, first,
      5' Rapid amplification of cDNA end (RACE) was used to determine GAT1
      transcriptional starting sites in neonatal mouse cerebral cortex and intestine,
      adult mouse brain and adult rat testis. The products of 5'RACE were confirmed by
      DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral
      cortex and adult mouse brain starts at the same site (inside of exon 1), while in
      mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the
      transcript of GAT1 has an additional untranslation exon to the 5' direction.

PMID- 11453550
TI  - Directional migration of leukocytes: their pathological roles in inflammation and
      strategies for development of anti-inflammatory therapies.
AB  - Directional migration of leukocytes is indispensable to innate immunity for host
      defense. However, recruitment of leukocytes to a site of tissue injury also
      constitutes a leading cause for inflammatory responses. Mechanistically, it
      involves a cascade of cellular events precisely regulated by temporal and spatial
      presentation of a repertoire of molecules in the migrating leukocytes and their
      surroundings (microenvironments). Here I will summarize the emerging evidence
      that has shed lights on the underlying molecular mechanism for directional
      migration of leukocytes, which has guided the therapeutical development for
      innovative anti-inflammatory medicines.

PMID- 11453551
TI  - The involvement of p38 MAPK in transforming growth factor beta1-induced apoptosis
      in murine hepatocytes.
AB  - We reported in this manuscript that TGF-beta1 induces apoptosis in AML12 murine
      hepatocytes, which is associated with the activation of p38 MAPK signaling
      pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF
      beta1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF
      beta1 activates p38. Furthermore, over-expression of dominant negative mutant p38
      also reduced the TGF-beta1-induced apoptosis. The data indicate that the
      activation of p38 is involved in TGF-beta1-mediated gene expression and
      apoptosis.

PMID- 11453552
TI  - The expression and antigenicity identification of recombinant rat TGF-beta1 in
      bacteria.
AB  - In order to study structure-function details of TGF-beta1, the recombinant mature
      form of rat TGF-beta1 was expressed in bacteria. Synthesis of the 112 amino-acid
      carboxyl-terminal part of TGF-beta1 (amino acid 279-390) was controlled by an
      inducible gene expression system based on bacteriophage T7 RNA polymerase. This
      system allowed an active and selective synthesis of recombinant TGF-beta1. The
      molecular weight of expressed TGF-alpha1 monomer determined on SDS-polyacrylamide
      gel under reducing conditions was about 13 kD. Serial detergent washes combined
      with a single gel-filtration purification step were sufficient to purify the
      expression product to homogeneity. Amino-terminal sequencing revealed that the N
      terminal of the recombinant protein was identical to the published data. In
      Western blot analysis the recombinant polypeptide showed excellent antigenicity
      against polyclonal TGF-beta1 antibody. The mature recombinant rat TGF-beta1
      expressed in this study provides a useful tool for future detailed structural and
      functional studies.

PMID- 11453553
TI  - Co-localization of chicken DNA topoisomerase IIalpha, but not beta, with sites of
      DNA replication and possible involvement of a C-terminal region of alpha through
      its binding to PCNA.
AB  - Clones for DNA topoisomerase IIalpha and beta (topo-IIalpha and beta) were
      isolated from a cDNA expression library of chicken MSB-1 cells by
      immunoscreening. The deduced sequences of chicken topo-IIalpha and beta were
      about 80% identical for the N-terminal ATPase domain and the central core domain
      but only 37% for the C-terminal domain. Polyclonal antibodies were raised against
      C-terminal polypeptides specific to topo-IIalpha and beta. Indirect
      immunofluorescence with these antibodies to chicken embryonic fibroblasts
      demonstrated that topo-IIalpha was distributed in discrete intranuclear spots,
      which coincided with sites of DNA replication as indicated by incorporation of 5
      bromo-2'-deoxyuridine, whereas topo-IIbeta was distributed rather uniformly
      within a nucleus. Examination of intranuclear distribution patterns of chimeric
      constructs between topo-IIalpha and beta suggested that a sequence region
      (residues 1280-1294) in the C-terminal domain of topo-IIalpha was effective in co
      localization with sites of DNA replication. This region consists of a QTxhxF
      motif (x, any residue; h, hydrophobic residue) followed by a KR-rich sequence,
      which resembles those found in several proteins known to associate with
      proliferating cell nuclear antigen (PCNA) or targeted to the replication factory.
      An in vitro pull-down assay with glutathione-S-transferase-PCNA and (His)6-tagged
      truncated forms of topo-IIalpha demonstrated that polypeptides containing the
      above region (residues 1158-1553 or 1158-1294) bound to PCNA in vitro.

PMID- 11453554
TI  - Isolation and characterization of two novel retrotransposons of the Ty1-copia
      group in oat genomes.
AB  - Two repetitive sequences, As32 and As22, of 826 and 742 bp, respectively, were
      isolated from Avena strigosa (As genome). Databank searches revealed their high
      homology to different segments of the family of Ty1-copia retrotransposons.
      Southern hybridization showed them to be present in diploid and polyploid oat
      species. Polymerase chain reaction with primers designed to amplify the segment
      between them showed that As32 and As22 sequences are composed of two different
      Ty1-copia retrotransposons. The segment amplified from the pAs32 insert was 2,264
      bp long and contained the entire GAG and AP domains, and more than half of the IN
      domain. This new element has been designated TAS-1 (transposon, A. strigosa, 1)
      and appears to contain a long open reading frame that encodes a polypeptide of
      625 amino acids. Slot-blot and fluorescence in situ hybridization analyses
      revealed it to be a component of both A- and D-genome chromosomes. Further, the
      chromosomes involved in one C-A intergenomic translocation in A. murphyi (AC
      genomes), one C-D intergenomic translocation in A. byzantina cv. Kanota (ACD
      genomes), and two C-D intergenomic translocations in A. sativa cv. Extra Klock,
      were identified. Based on its physical distribution and Southern hybridization
      pattern, a parental retro-transposon represented by TAS-1 appears to have been
      active at least twice during the evolution of the genomes in species of Avena.

PMID- 11453555
TI  - Spermatogenic failure in male mice with four sex chromosomes.
AB  - There is accumulating evidence that meiosis, like mitosis, is monitored by a
      number of checkpoints. In mammals, the presence of asynapsed chromosomes at
      pachytene triggers a checkpoint (the pachytene or synapsis checkpoint) that
      removes cells via a p53-independent apoptotic pathway. In the special case of the
      sex bivalent in males, it is pseudoautosomal region (PAR) asynapsis that triggers
      the checkpoint. In male mice with three sex chromosomes (XYY or XYY(*X)) some
      pachytene spermatocytes achieve full (trivalent) PAR synapsis, but in many cells
      one sex chromosome remains as a univalent, thus triggering the checkpoint. Sperm
      counts in these males have been shown to be positively correlated with trivalent
      frequencies. In the present study sperm production and levels of sex chromosome
      synapsis were studied in mice with four sex chromosomes (XYYY(*X)) and
      XYY(*X)Y(*X)). These mice proved to be more severely affected than XYY or XYY(*X)
      mice. Nevertheless, pachytene synaptonemal complex analysis revealed that full
      PAR synapsis was achieved through the formation of radial quadrivalents or
      through the formation of two sex bivalents in 21%-49% of cells analysed. Given
      these levels of full PAR synapsis, the sperm counts were consistently lower than
      would have been predicted from the relationship between levels of PAR synapsis
      and sperm counts in mice with three sex chromosomes. It has been suggested that
      the inactivation of the asynapsed non-PAR X and Y axes of the XY bivalent of
      normal males (MSCI), which occurs during meiotic prophase, may be driven by Xist
      transcripts originating from the X. If this is the case, the non-PAR Y axes of YY
      and YY(*X) bivalents would fail to undergo MSCI. This could be cell lethal,
      either because of 'inappropriate' Y gene expression, or because the non-PAR Y
      axis may now trigger the synapsis checkpoint.

PMID- 11453556
TI  - Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is
      overexpressed in tumour cells.
AB  - The inner centromere protein (INCENP), which has previously been described in
      chicken, frog and mouse, is required for correct chromosome segregation and
      cytokinesis. We have identified the human INCENP gene by library screening and
      reverse transcription-polymerase chain reaction (RT-PCR) and localized it to
      chromosomal region 11q12. HsINCENP is a single-copy gene that consists of 17
      exons and covers 25 kb of genomic DNA. The gene is expressed at highest levels in
      the colon, testis and prostate, consistent with its likely role in cell
      proliferation. HsINCENP encodes a highly basic protein of 915 amino acids that
      localizes to metaphase chromosomes and to the mitotic spindle and equatorial
      cortex at anaphase. Recently we showed that INCENP is stockpiled in a complex
      with the Aurora-B/XAIRK2 kinase in Xenopus eggs. Here we demonstrate that,
      consistent with such an interaction, the two proteins colocalize on human
      metaphase chromosomes. Levels of Aurora-B are increased in several human cancers,
      and we show here that HsINCENP protein levels are also significantly increased in
      several colorectal cancer cell lines.

PMID- 11453557
TI  - Human intrachromosomal telomeric-like repeats: sequence organization and
      mechanisms of origin.
AB  - The intrachromosomal location of (T2AG3)n telomeric sequences has been reported
      in several species. It was proposed that interstitial telomeres (ITs) originated
      through telomeric fusion of ancestral chromosomes. However, the data so far
      obtained derive mainly from cytogenetic observations. Cloning and database
      searching of human IT sequences allowed us to identify three classes: (i) short
      ITs, composed of few, essentially exact T2AG3 units; (ii) subtelomeric ITs,
      composed of larger arrays (several hundred base pairs) including many degenerate
      units within subtelomeric domains; (iii) fusion ITs, in which two extended
      stretches of telomeric repeats are oriented head-to-head. The number of short ITs
      is over 50 and subtelomeric ITs are probably present at all chromosomal ends.
      Surprisingly, the telomeric sequence in 2q13 remains the only fusion IT so far
      characterized, and evidence presented here suggests that another member of this
      class may be present in 1q41. Different molecular mechanisms generated the three
      classes. In particular, several short ITs interrupt precisely repetitive elements
      or are flanked by direct repeats of 10-41 bp, and are conserved in gorilla and
      chimpanzee. These features strongly suggest that telomeric repeats were inserted
      at intrachromosomal sites through the repair of double-strand breaks that
      occurred in the germline during evolution.

PMID- 11453558
TI  - Chromatin organization and its relation to replication and histone acetylation
      during the cell cycle in barley.
AB  - We have studied the replication time, nuclear organization and histone
      acetylation patterns of distinct chromatin domains [nucleolus organizers (NORs),
      centromeres, euchromatin and heterochromatin] of barley during the cell cycle.
      The Rabl orientation of chromosomes, with centromeres and telomeres located at
      opposite nuclear poles, was found to be maintained throughout interphase.
      Replication started at the rDNA loci within nucleoli and then proceeded from the
      euchromatic distal chromosome regions toward the heterochromatic pole. Centromere
      association frequently occurred in mid- and late S-phase, i.e., during and after
      centromere replication. Euchromatin, centromeres and heterochromatin were found
      to be enriched in acetylated histone H4 (except for lysine 16) during their
      replication; then deacetylation occurred. The level of deacetylation of H4 in
      heterochromatin was more pronounced than in euchromatin. Deacetylation is
      finished in early G2-phase (lysine 8) or may last until mitosis or even the next
      G1-phase (lysines 5 and 12). The NORs were found to be most strongly acetylated
      at lysines 5 and 12 of H4 during mitosis, independently of their potential
      activity in nucleolus formation and rDNA transcription. The acetylation pattern
      of chromosomal histone H3 was characterized by low acetylation intensity at
      centromeres (lysines 9/18) and pericentromeric regions (lysine 14) and more
      intense uniform acetylation of the remaining chromatin; it remained fairly
      constant throughout the cell cycle. These results have been compared with the
      corresponding data published for mammals and for the dicot Vicia faba. This
      revealed conserved features as well as plant- or species-specific peculiarities.
      In particular, the connection of acetylation intensity of H4 at microscopically
      identifiable chromatin domains with replicational but not with transcriptional
      activity during the cell cycle seems to be conserved among eukaryotes.

PMID- 11453559
TI  - Involvement of histone H4 acetylation in the epigenetic inheritance of different
      activity states of maternally and paternally derived genomes in the mealybug
      Planococcus citri.
AB  - Modification of histones by acetylation is a well-known mechanism for the
      establishment and maintenance of specific chromatin structures with different
      activity states. In Planococcus citri males the paternal genome, early in
      development, becomes mostly inactive and heterochromatic. As we had not found
      methylation in the genome of P. citri, we analyzed the acetylation state of
      histone H4. We report here that, in males, differences in the level of histone H4
      acetylation are indeed present in the two genomes of different parental origin;
      these differences were confirmed by treatment with the histone deacetylase
      inhibitor Trichostatin A. There is also evidence of acetylation of histone H4 on
      metaphase chromosomes. Our data therefore suggest a role of histone H4
      acetylation in the imprinting of the paternal genome in P. citri males, thus
      supporting a role of modification of chromatin-related structural proteins in the
      epigenetic transmission of imprinting.

PMID- 11453560
TI  - Botulinum toxin treatment for cricopharyngeal dysfunction.
AB  - Hypertonicity and spasticity of the cricopharyngeal muscle (CPM) often result in
      dysphagia characterized by difficulty passing a bolus through the upper
      esophageal sphincter. Past treatments for this problem have included mechanical
      dilation and endoscopic and transcervical cricopharyngeal myotomy. More recently,
      botulinum toxin injections into the CPM have been successful, but only in
      isolated case studies and small series. This study reports pre- and post
      botulinum toxin A injection results for 12 subjects, including patient ratings of
      symptom severity, changes noted during modified barium swallow studies, and, in
      some cases, manometry of the upper esophageal sphincter. Results indicate that
      botulinum toxin A treatment provided significant improvement in swallowing as
      indicated by patient symptom ratings and investigator ratings of function from
      modified barium swallow studies. Greater improvement was seen in those with more
      isolated CPM or Xth nerve dysfunction rather than those with more global
      dysphagia abnormalities.

PMID- 11453561
TI  - Botulinum toxin for UES dysfunction: therapy or poison?

PMID- 11453562
TI  - Botulinum toxin in the treatment of cricopharyngeal dysphagia.
AB  - Dysphagia is a common symptom in various neurological disorders affecting
      pharyngeal functions. Cricopharyngeal dysfunction is one of the major findings in
      these patients. The most effective treatment for restoring normal swallowing
      function in persistent cricopharyngeal dysfunction is cricopharyngeal myotomy,
      especially when mechanical obstruction or a well-localized neuromuscular
      dysfunction, such as a cricopharyngeal muscle spasm, is present. However, when
      there is a more diffuse neurological disorder present the results of surgery are
      more disappointing. In unclear cases, or in patients with temporary problems, no
      good method other than swallowing training, bougienage, and tube feeding are
      available. During the past decade, botulinum toxin has been found to be of
      therapeutic value in the treatment of a variety of neurological disorders
      associated with inappropriate muscular contractions such as torticollis and
      spasmodic dysphonia. Recently, injections of botulinum toxin in patients with
      cricopharyngeal muscle dysfunction have been reported to result in marked relief
      of dysphagia. In this article we describe our experiences with botulinum toxin
      injections to treat four patients suffering from deglutition problems and
      cricopharyngeal dysphagia of different origins. Botulinum toxin was injected into
      the cricopharyngeus muscle that was identified by endoscopy under general
      anesthesia. In this study, no major side effects were observed. Three patients
      obtained a significant improvement of esophageal symptoms after the first
      injection. The treatment had limited effect in one patient who had reflux disease
      and only slight cricopharyngeus dysfunction.

PMID- 11453563
TI  - Swallowing physiology of sequential straw drinking.
AB  - The goal of this study was to examine deglutitive physiology during sequential
      straw drinking in healthy young adults (n = 15) to learn how sequential
      swallowing differs from single swallows. The physiology of single swallows has
      been studied extensively in healthy adults and in adults with a variety of
      debilitating conditions, but the physiology of sequential swallows has not been
      studied adequately. Videofluoroscopic analysis revealed three distinct patterns
      of hyolaryngeal complex (HLC) movement during sequential straw swallows: opening
      of the laryngeal vestibule after each swallow (Type I, 53%), continued vestibule
      closure after each swallow (Type II, 27%), and interchangeable vestibule opening
      and closing during the swallow sequence (Mixed, 20%). Unlike discrete swallowing,
      the onset of the pharyngeal swallow occurred when the bolus was inferior to the
      valleculae in the majority of subjects and was significantly associated with HLC
      movement pattern. The leading bolus edge was inferior to the valleculae at
      swallow onset for Type II movement patterns. For Type I movement patterns, bolus
      position at swallow onset was randomly distributed between three anatomical
      positions: superior to the valleculae, at the level of the valleculae, and
      inferior to the valleculae. Preswallow pharyngeal bolus accumulation, which is
      common during mastication, was evident and significantly associated with the HLC
      pattern of opened laryngeal vestibule after each swallow. These data suggest that
      in healthy young adults, sequential swallows differ physiologically from discrete
      swallows and indicate substantial variability in deglutitive biomechanics.

PMID- 11453564
TI  - Magnetoencephalographic response characteristics associated with tongue movement.
AB  - Whole-head magnetoencephalography (MEG) was employed to study the sources of
      activation evoked by both active tongue movement and swallowing in five healthy
      subjects. Evoked magnetic fields were adequately explained in both paradigms by a
      time-varying single-dipole model which localized in the tongue in all subjects.
      No additional brain sources were detectable. Therefore, MEG detects fields
      associated with tongue movement that best fit a single-dipole source in the
      tongue. Future electrophysiological brain activation studies where tongue
      movement is likely should be aware of this observation since the tongue behaves
      like a strong current dipole.

PMID- 11453565
TI  - Repetitive proximal esophageal contractions: a new manometric finding and a
      possible further link between Parkinson's disease and achalasia.
AB  - Repetitive, spontaneous contractions of the proximal esophagus have recently been
      identified as a feature of achalasia. This article documents similar findings in
      six patients with Parkinson's disease. Parkinson's disease and achalasia share
      many common features neurologically. Both have Lewy bodies in the esophageal
      myenteric plexuses and the substantia nigra, in addition to evidence of
      degeneration of the dorsal motor nucleus of the vagus. The esophageal features
      radiologically and manometrically are also similar. Repetitive proximal
      esophageal contractions may represent another link between these diseases. They
      have also been reported in scleroderma. We speculate that the common link between
      all three disease processes may be poor distensibility of the esophagus.

PMID- 11453566
TI  - Videomanometric analysis of supraglottic swallow, effortful swallow, and chin
      tuck in patients with pharyngeal dysfunction.
AB  - Simultaneous videoradiography and solid-state manometry (videomanometry) was
      performed in 8 patients (4 women, 4 men; age range = 46-81 years, mean age = 70
      years) with pharyngeal dysfunction. Five patients had severe pharyngeal
      dysfunction with frequent misdirected swallows. Three patients had moderate
      pharyngeal dysfunction with delayed initiation of pharyngeal swallow. Three
      different swallowing techniques were used: supraglottic swallow, effortful
      swallow, and chin tuck. Ten video radiographic variables and six manometric
      variables were analyzed. Contrast media penetration to the airways was analyzed
      regarding number of events and level of penetration. Supraglottic swallow,
      effortful swallow, and chin tuck did not reduce the number of misdirected
      swallows, but effortful swallow and chin tuck significantly (p = 0.008) reduced
      the depth of contrast penetration into the larynx and trachea. There was no
      significant improvement of pharyngeal retention. Chin tuck reduced the distance
      between the thyroid and the hyoid and the distance between the mandible and the
      hyoid. No other measured variable was significantly altered. This study shows
      that none of the different swallowing techniques reduced the number of
      misdirected swallows. However, there was a significantly reduced depth of the
      misdirected swallows. The swallowing techniques did not seem to prevent the
      occurrence of retention or improve weak pharyngeal constrictor muscles in this
      group of patients with severe to moderate dysfunction.

PMID- 11453567
TI  - Dementia with oropharyngeal dysphagia and myopathy.
AB  - A 72-year-old man was referred for geriatric evaluation with a view toward
      placement in institutional care. He presented originally to an internal medicine
      team with a six-month history of weight loss, constipation, generalized weakness,
      and apathy; investigations to rule out an underlying neoplasm were negative.
      Interdisciplinary assessment revealed coexisting dementia, myopathy, and
      oropharyngeal dysphagia. These findings prompted further diagnostic evaluation
      and a diagnosis of inflammatory myopathy with associated oropharyngeal dysphagia
      and dementia was made. The dementia, myopathy, and oropharyngeal dysphagia
      responded to steroids and rehabilitation and the patient regained his
      independence.

PMID- 11453568
TI  - Objective measures of dysphagia complexity in children related to suckle feeding
      histories, gestational ages, and classification of their cerebral palsy.
AB  - Data collected during the routine assessment of 117 dysphagic children with
      cerebral palsy have been related to both suckle feeding histories and gestational
      ages and to the classification of cerebral palsy. In addition, a concurrent
      survey involving 281 children with cerebral palsy in special schools was
      undertaken which revealed that the sample of referred children appeared to be a
      true representation of a wider population of dysphagic children with cerebral
      palsy. A Feeding Difficulty Symptom Score (FDSS) describes the severity of
      swallowing symptoms reported. A numerical Dysphagia Complexity Index (DCI)
      quantifies numerically the neurological complexity of the swallowing difficulty.
      The FDSS correlates closely with the DCI. Twenty-seven percent of mothers of the
      children who were referred for advice on their present swallowing difficulties
      stated that they recalled no suckle feeding problems. However, there was no
      difference in the severity of present swallowing difficulties between those
      infants who suckle fed well and those who experienced severe difficulties. Those
      referred children with cerebral palsy born at term exhibited more complex later
      swallowing problems and were more likely to be classified as athetoid than those
      born preterm.

PMID- 11453569
TI  - Initial clinical and demographic predictors of swallowing impairment following
      acute stroke.
AB  - Swallowing impairment (dysphagia) is a frequent sequela of acute stroke; however,
      the ability to accurately detect dysphagia at the bedside and predict which
      patients may be at risk of dysphagic complications, such as aspiration, remains
      limited. Despite this, clinical assessment batteries continue to be the first
      point of assessment for acute dysphagia. We examined the predictive value of
      clinical factors suggestive of swallowing dysfunction in an attempt to identify
      the important independent clinical signs at initial presentation that are
      associated with dysphagia, aspiration, and the combined variable aspiration
      and/or penetration (ASPEN) in acute stroke patients. For the purposes of this
      study, dysphagia was defined as a disorder of bolus flow. Aspiration was defined
      as entry of swallowed material below the level of the true vocal cords which was
      not expectorated. The clinical items identified as independent predictors of
      dysphagia (measured radiographically) at initial presentation were age > 70
      years, male gender, disabling stroke (Barthel score < 60), palatal weakness or
      asymmetry, incomplete oral clearance, and impaired pharyngeal response
      (cough/gurgle). The clinical predictors of aspiration (determined
      radiographically) at initial presentation were delayed oral transit and
      incomplete oral clearance. Incorporating clinical signs, such as those identified
      by this study, into clinical assessments of swallowing impairment may increase
      their predictive utility.

PMID- 11453570
TI  - Experience with the chin tuck maneuver in postesophagectomy aspirators.
AB  - Aspiration is a common finding in the postesophagectomy barium swallow that often
      necessitates premature termination of the study prior to complete evaluation of
      the gastric conduit. More importantly, aspiration may play a significant role in
      the high incidence of postoperative pulmonary complications in this population.
      The chin tuck maneuver is a postural technique that reduces and often eliminates
      aspiration in swallowing-impaired patients. To evaluate the ability of the chin
      tuck maneuver to prevent aspiration during radiographic examination of the
      gastric conduit, the technique was used in 21 esophagectomy patients who
      aspirated during a swallowing evaluation combining the barium swallow and
      videofluoroscopy. Aspiration was eliminated in 81% of aspirators using the chin
      tuck maneuver. The results of this study demonstrate that the chin tuck maneuver
      is a simple technique that should be attempted in patients who aspirate
      postesophagectomy during radiographic imaging studies that require multiple
      swallows of contrast materials. Combining the barium swallow with the
      videofluoroscopic evaluation of swallowing provides objective documentation of
      both the structural integrity of the gastric conduit and swallowing function in
      patients after esophagectomies who are at high risk for postoperative morbidity.

PMID- 11453571
TI  - Ectopic lingual thyroid as unusual cause of severe dysphagia.
AB  - Ectopic lingual thyroid is an uncommon embryological aberration characterized by
      the presence of thyroid tissue located in a site different from the pretracheal
      region as in the normal. Lingual thyroid is the most frequent ectopic location of
      the thyroid gland, although its clinical incidence varies between 1:3000 and
      1:10,000. We present the case of a 26-year-old woman who presented severe
      dysphagia caused by a mass located on the base of the tongue in the midline. An
      endoscopic partial removal of the ectopic tissue allowed her to rapidly regain
      her swallowing capacity. The literature regarding the incidence and diagnosis of
      lingual thyroid is reviewed and the possibilities of treatment discussed.

PMID- 11453572
TI  - Spindle cell lipoma of the hypopharynx.
AB  - Larynx and hypopharynx lipomas are reported to account for approximately 0.6% of
      benign laryngeal neoplasms. Spindle cell lipoma is a histologically distinct
      variant characterized by mature adipocytes mixed with collagen-forming spindle
      cells; only one case of spindle cell lipoma of the larynx has been previously
      reported. We here describe a new case of spindle cell lipoma of the pyriform
      sinus successfully treated by means of endoscopic surgical excision. A 77-year
      old woman with a 40-year history of dysphagia reported that the condition had
      markedly worsened over the three years before she came to us. She had difficulty
      swallowing even semisolid food and she experienced occasional nasal regurgitation
      of liquid or solid food. Flexible videolaryngoscopy showed a very large mass,
      covered by normal mucosa that almost totally occupied the right pyriform sinus
      and was apparently attached to the right arytenoid. Functional endoscopic study
      and videofluoroscopy of swallowing showed that the bolus progressed exclusively
      in the left pyriform sinus, with postdeglutitory pooling in the right pyriform
      sinus and a reflux toward the valleculae during consecutive deglutitions.
      Computed tomography demonstrated that the hypopharyngeal mass had low attenuation
      values and negative densitometry. The entire mass was surgically removed during
      suspension microlaryngoscopy. The histological sections showed mature adipocytes
      mixed with small and slender spindle cells. Postoperative endoscopic and
      videofluorosocpic deglutition studies revealed the recovery of normal swallowing.
      This case indicates that hypopharyngeal lipomas should be included in the
      differential diagnosis of slowly occurring swallowing impairments.

PMID- 11453573
TI  - Successful botulinum toxin treatment of dysphagia in a young child with nemaline
      myopathy.

PMID- 11453574
TI  - Non-invasive assessment of myocardial perfusion by intravenous contrast
      echocardiography: state of the art.
AB  - Many technical problems, related to both imaging instrumentation and contrast
      agents, have to be taken into account before attempting non-invasive evaluation
      of myocardial perfusion by intravenous contrast media injection. Potentials and
      pitfalls of first generation contrast agents (i.e. Levovist, Schering AG, Berlin,
      Germany) using intermittent harmonic angio imaging and of second generation
      contrast media (i.e. SonoVue, Bracco SpA, Milan, Italy) using real-time perfusion
      imaging in the non-invasive assessment of myocardial perfusion were described and
      discussed. We still need more solid data before introducing intravenous
      myocardial echocardiography into the clinical arena. However, convincing data
      from several research laboratories are paving the way for the widespread use of
      this new method in clinical practice.

PMID- 11453575
TI  - Tumor necrosis factor-alpha and cardiovascular diseases.
AB  - Tumor necrosis factor (TNF)-alpha is a potent inducible cytokine with pleiotropic
      biological effects, now implicated as a mediator of various physiologic and
      pathophysiologic events including inflammation, cell survival, growth,
      differentiation and apoptosis. TNF-alpha functions within a complex and tightly
      regulated cytokine network, activating multiple signal transduction pathways and
      inducing or suppressing a wide variety of genes, including those encoding for
      other cytokines, adhesion molecules and the inducible nitric oxide synthase. TNF
      alpha has recently been implicated as a transducer of cardiovascular diseases,
      namely coronary artery disease and congestive heart failure. This review will
      summarize established and newer findings on this molecule.

PMID- 11453576
TI  - Imaging of the posterior descending coronary artery. The last frontier in
      echocardiography.
AB  - BACKGROUND: Non-invasive color Doppler imaging of the left anterior descending
      coronary artery has been described, but imaging of the posterior descending
      coronary artery (PD) has never been reported. The aim of this paper was to
      describe color Doppler imaging and flow reserve of the PD, regardless of its
      origin from the right or circumflex coronary artery, in different settings such
      as acute myocardial infarction or coronary stenting. METHODS: A C256 Acuson
      Sequoia ultrasound system connected to a standard 3.5 MHz transducer was used.
      Neither a contrast agent nor harmonic or power Doppler imaging was used. However,
      the Nyquist limit of color Doppler was reduced to 12 cm/s. Patients were examined
      in the apical 2-chamber view, with the coronary sinus ostium imaged in the short
      axis until a diastolic flow signal close to the epicardial layer was detected.
      Pulsed Doppler confirmed an anterograde, doming systolic and monophasic
      decrescendo diastolic flow. Adenosine was intravenously infused at the standard
      dose of 140 microg/kg/min over 90 s in order to elicit maximal microcirculatory
      dilation. The resting and hyperemic peak diastolic flow velocities were measured
      and the coronary flow reserve was calculated as the ratio between hyperemic and
      resting peak diastolic flow velocities. RESULTS: This simple bedside technique
      provided crucial information about several important issues: 1) arterial patency
      after thrombolysis; 2) evaluation of the physiologic impact of a coronary
      stenosis, with implications on the detection of a critical stenosis; 3)
      reperfusion imaging of perforating branches after myocardial infarction; 4) post
      stent assessment of coronary flow reserve. CONCLUSIONS: This paper shows, for the
      first time, that non-invasive imaging of the PD by non-contrast transthoracic
      Doppler is feasible and that the coronary flow reserve is measurable even in
      critical conditions. More studies are needed to assess the feasibility of PD
      imaging in different clinical settings and the potential benefit of contrast
      agents in improving the evaluation of coronary flow.

PMID- 11453577
TI  - Comparison between single and double internal mammary artery grafts: results over
      ten years.
AB  - BACKGROUND: In view of the superior patency of the internal mammary artery (IMA),
      grafting of this vessel to the left anterior descending artery is advantageous in
      terms of survival and quality of life; the benefits of using both the mammary
      arteries remain unproved. METHODS: Among the patients operated upon during the
      period 1988-1990, we randomly selected 150 patients in whom one IMA (group 1) was
      grafted and 150 patients in whom both IMAs (group 2) were grafted. The survival
      and event free curves of these two groups of patients were designed using the
      Kaplan-Mayer method; the log-rank test was used to assess the statistical
      difference between the curves and to determine whether, in the long term,
      benefits were superior in patients in whom both IMAs were grafted. RESULTS:
      Patients in group 1 were older (p = 0.002). In this group there were more
      patients with diabetes (p = 0.004) and with peripheral vascular disease (p =
      0.047). There were more female patients in group 2 (p < 0.02) and more coronary
      vessels were grafted (p = 0.03). Follow-up was complete (100%) and equivalent in
      duration for both groups (109 +/- 30 months for group 1 and 110 +/- 33 months for
      group 2, p = NS). The survival rate at 10 years was equal for both groups (82.5
      +/- 3.4% for group 2 vs 82.9 +/- 3.2% for group 1, p = NS) and so was the freedom
      from cardiac death. The provocative test for myocardial ischemia was more
      frequently positive in group 1 than in group 2 (21 vs 10 cases, p = 0.054).
      Freedom from new myocardial infarction (p = NS), angina recurrence (p = NS) and
      reoperation (p = NS) was equally distributed during follow-up. Group 2 patients
      more frequently necessitated coronary angioplasty but the difference was not
      significant (p = 0.17). Survival free from angina recurrence, new myocardial
      infarction, coronary angioplasty and reoperation was more frequent in group 2
      (respectively 74.6 +/- 3.8 vs 70.7 +/- 4.1%) but the difference was not
      statistically significant (p = NS). CONCLUSIONS: After 12 years of follow-up,
      patients submitted to grafting of a single IMA more frequently presented with
      inducible myocardial ischemia, but neither survival nor the quality of life were
      superior in the patients in whom both IMAs were grafted.

PMID- 11453578
TI  - Surgical treatment of secundum atrial septal defect in patients older than 50
      years.
AB  - BACKGROUND: The aim of this study was to verify if surgery is beneficial for
      patients older than 50 years. METHODS: Sixty-five patients older than 50 years
      were operated for a secundum atrial septal defect between November 1974 and
      November 1998. Preoperative data were obtained from hospital records;
      postoperative data from written questionnaires or direct telephone interviews. A
      comparison of pre and postoperative data was possible in 53 patients. RESULTS:
      The operative mortality was 0%. One patient died of a thromboembolic complication
      32 days after surgery. The mean follow-up was 9 +/- 6 years. After surgery,
      clinical improvement occurred in 22 patients (41.5%) with the majority of them
      (69.8%) being asymptomatic or only mildly symptomatic. The occurrence of atrial
      fibrillation/flutter did not decrease after surgery (39.6 vs 26.4%). A
      thromboembolic event occurred in 2 patients before surgery and in 2 patients
      postoperatively; all of them had supraventricular arrhythmias and were not taking
      anticoagulants. CONCLUSIONS: Surgical closure of atrial septal defects in
      patients older than 50 years is feasible. The mortality is low. In this age
      group, surgery has a beneficial effect on the clinical status of the patients but
      not on the occurrence of supraventricular arrhythmias that can affect morbidity
      and mortality in patients who are not treated with anticoagulants.

PMID- 11453579
TI  - Surgical treatment of secundum atrial septal defect in the older patient.

PMID- 11453580
TI  - Altered values of heart rate variability in patients with relapse of atrial
      fibrillation during the first week after electrical cardioversion: preliminary
      data.
AB  - BACKGROUND: It has not so far been elucidated whether the autonomic nervous
      system plays a role in the pathogenesis of atrial fibrillation relapse after
      electrical cardioversion. METHODS: In 40 consecutive patients with atrial
      fibrillation (22 males, 18 females, mean age 60 +/- 2 years) submitted to
      successful electrical cardioversion (external in 26 and low-energy internal in
      14) we evaluated the heart rate variability (24-hour Holter recording)
      immediately after restoration of sinus rhythm in order to assess the cardiac
      sympatho-vagal drive. RESULTS: Patients with atrial fibrillation relapse within
      the first week of electrical cardioversion were characterized by a significantly
      higher low/high frequency ratio. CONCLUSIONS: Despite the heterogeneity of the
      studied population (concerning both the therapy and etiology of atrial
      fibrillation), our data strongly suggest that the evaluation of the low/high
      frequency ratio by means of power spectral analysis immediately after electrical
      cardioversion is a useful tool for the identification of those patients who are
      prone to atrial fibrillation recurrence. Our conclusions are supported by the
      finding of high positive and negative predictive values for the low/high
      frequency ratio both in the 24-hour period and during daytime.

PMID- 11453581
TI  - Pacemaker-induced mitral regurgitation: prominent role of abnormal ventricular
      activation sequence versus altered atrioventricular synchrony.
AB  - BACKGROUND: Functional mitral regurgitation is a hemodynamic adverse consequence
      of right ventricular apical pacing that profoundly modifies the contraction and
      relaxation of the left ventricle by inverting and delaying its activation
      sequence. The aim of this study was to analyze by Doppler echocardiography in the
      acute setting the true incidence and the mechanism responsible for the right
      ventricular apical pacing-induced mitral regurgitation. METHODS: We studied 27
      consecutive patients submitted to pacemaker implantation (VVI n = 9; DDD n = 18)
      because of bradyarrhythmias. The exclusion criteria were structural cardiac
      disease and permanent atrioventricular block. Patients underwent Doppler
      echocardiographic examination during both spontaneous rhythm (pacemaker off) as
      well as during programmed pacing at a rate of 70 b/min. In case of a double
      chamber pacemaker, a non-optimized atrioventricular delay of 150 ms was chosen.
      RESULTS: Two groups were identified: 11 patients with (Group 1, mean age 71 +/- 7
      years) and 16 patients without (Group 2, mean age 71 +/- 4 years) new-onset
      pacing-induced mitral regurgitation. The incidence of mitral regurgitation was
      found to be higher during DDD (33%) than during VVI (24%) pacing mode. The
      relationship between gender and the occurrence of pacing-induced mitral
      regurgitation was striking: 10/13 women (77%) presented with mitral regurgitation
      during acute right ventricular apical pacing while this complication occurred in
      only 1/14 men (7%). Moreover, analysis of variance (ANOVA) and post-hoc pairwise
      multiple comparison showed an increased size of the mitral apparatus, as defined
      by the enlargement of the annulus (long axis 28 +/- 3 vs 23 +/- 2 mm; short axis
      25 +/- 3 vs 20 +/- 3 mm, p = 0.05) and the lengthening of the anterior mitral
      leaflet (23 +/- 4 vs 18 +/- 2 mm, p = 0.05) and chordae tendineae (16 +/- 3 vs 13
      +/- 2 mm, p = 0.05). This was probably related to the high female prevalence
      (91%) in Group 1 as compared to the control group (50 healthy subjects; 17 men,
      33 women; mean age 71 +/- 8 years). No significant differences were observed
      between Group 2 and controls. CONCLUSIONS: Our study confirmed that functional
      mitral regurgitation is a frequent consequence of right ventricular apical
      pacing. Despite the maintenance of normal atrioventricular synchrony, we found
      that the pathway for ventricular depolarization was the critical determinant of
      normal mitral valve function. Such data show the importance of the preservation
      of a normal ventricular activation sequence during permanent cardiac pacing where
      it is technically feasible. Female patients seemed to be exposed to a higher risk
      of pacing-induced mitral regurgitation due to an anatomic predisposing condition
      of the mitral apparatus and to the left ventricular dyssynchronous contraction
      secondary to right ventricular apical pacing.

PMID- 11453582
TI  - Comparison of defibrillation thresholds using monodirectional electrical vector
      versus bidirectional electrical vector.
AB  - BACKGROUND: Currently, two main lead configurations are used for implantable
      cardioverter-defibrillators (ICD). One generates a monodirectional electrical
      vector by using the can surface as an active part (hot can) together with a right
      ventricular defibrillation coil. The other one (TRIAD) produces a bidirectional
      electrical vector by adding a proximal defibrillation electrode on the same lead.
      The purpose of this prospective study was to determine whether there is a
      difference between these configurations in terms of the acute defibrillation
      threshold (DFT). The secondary objective was to evaluate the possible sequential
      effect of successive arrhythmia induction and defibrillation shocks on the final
      DFT value. METHODS: In 44 patients (37 males, 7 females, mean age 59.18 +/- 12.05
      years; mean ejection fraction 35.21 +/- 11.69%), a Hot Can Ventak family ICD
      (Guidant, St. Paul, MN, USA) was implanted in a left pectoral pocket. During the
      implant procedure, step-down to failure DFT testing was performed twice in each
      patient using the two different above-mentioned configurations: the bidirectional
      and the monodirectional. The first configuration to be tested was determined by a
      1:1 randomization by center. RESULTS: The step-down DFT protocol was followed in
      35 patients. The average DFT was 8.6 +/- 4.0 J for TRIAD and 10.4 +/- 4.3 J for
      the monodirectional (p = 0.009) lead configuration; this represents a 16.3%
      decrease in the DFT using a bidirectional configuration. Furthermore, no
      relationship between the final DFT and the number of ventricular fibrillation
      inductions and shocks received was observed, confirming the secondary objective.
      CONCLUSIONS: Compared to the monodirectional electrical vector, the bidirectional
      electrical vector is clearly more beneficial for the patient.

PMID- 11453583
TI  - Permanent junctional reciprocating tachycardia in infants and children:
      effectiveness of medical and non-medical treatment.
AB  - BACKGROUND: The aim of this study was to identify, in children affected by
      permanent junctional reciprocating tachycardia (PJRT), the effective treatment.
      METHODS: Seventeen children (9 males, 8 females, mean age 59 +/- 62 months,
      median 24) affected by PJRT were referred to our Institute between the years 1987
      and 2000. RESULTS: Pharmacological therapy was successfully used in 14 patients:
      flecainide and propranolol in 5 of them, amiodarone alone in 5 and associated
      with propranolol in 2, propafenone alone in 1 and in association with sotalol in
      1. These drugs were given for a mean period of 54.5 +/- 49.8 months with
      resolution of the cardiomyopathy in 7/7 patients. Treatment had been continued
      for 3-6 months and there were no side effects. Nine patients were treated with
      radiofrequency transcatheter ablation, after 78 +/- 53.5 months of medical
      treatment, at a mean age of 150 +/- 16 months. The shortest endocardial
      ventriculo-atrial (VA) interval during tachycardia was recorded in all cases at
      the coronary sinus ostium (mean value of local VA-surface RP' interval -38 ms,
      range -24/-55 ms). Successful ablation of the anomalous pathway was obtained at
      this site in all patients (mean watts delivered 26 +/- 3 W, mean T degrees 64 +/-
      5 degrees C). During the follow-up period (mean 21 +/- 17 months) 2 patients with
      recurrences of PJRT underwent a second successful procedure. CONCLUSIONS: PJRT in
      pediatric patients can be successfully treated with antiarrhythmic drugs, this
      may allow delay of the highly effective radiofrequency ablation treatment until
      the children have reached an adequate growth.

PMID- 11453584
TI  - Cardiopulmonary exercise test in young women affected by anorexia nervosa.
AB  - BACKGROUND: The aim of this study was to evaluate exercise performance in
      patients affected by anorexia nervosa. METHODS: We studied 19 patients (all
      females, mean age 23.1 +/- 5.2 years) affected by anorexia nervosa (mean weight
      37.3 kg, body mass index 14.04 +/- 1.4 kg/m2) and 20 constitutionally thin women,
      matched for age, height and physical activity, with a body mass index < 19 kg/m2.
      All these women underwent clinical examination, standard ECG and a
      cardiopulmonary stress test. RESULTS: Patients affected by anorexia nervosa
      showed a lower heart rate and systolic blood pressure at peak exercise (148.8 +/-
      13.8 vs 171 +/- 9.2 b/min, p < 0.001, and 130 +/- 9.5 vs 152 +/- 11.2 mmHg, p <
      0.001), work load (85.5 +/- 15.1 vs 117.2 +/- 20.3 W, p < 0.001), rate-pressure
      product (19 371 +/- 2391 vs 25,986 +/- 2218 b/min/mmHg, p < 0.001), oxygen uptake
      (VO2) at rest and maximum VO2 (5.4 +/- 1.7 vs 7.1 +/- 1.1 ml/kg/min, p < 0.001,
      and 28.08 +/- 6.3 vs 40.2 +/- 7.1 ml/kg/min, p < 0.001), anaerobic threshold
      (15.7 +/- 1.9 vs 20.4 +/- 2.1 ml/kg/min, p < 0.001), VO2 during exercise (9.5 +/-
      1.2 vs 12.8 +/- 1.3 ml/min/W, p < 0.001), maximum minute ventilation (34.5 +/-
      9.9 vs 48.4 +/- 10.3 /min, p < 0.001), and oxygen pulse (7.2 +/- 2 vs 10.9 +/-
      2.4 ml/b, p < 0.001). CONCLUSIONS: These data show an abnormal working capacity
      and cardiovascular responses to exercise in patients affected by anorexia
      nervosa. The low VO2, both at rest and during exercise, allows them to maintain a
      relatively high level of physical activity, which contributes to increase the
      energy expenditure needed for weight loss.

PMID- 11453585
TI  - Facilitation of atrioventricular reentrant tachycardia by iatrogenic right bundle
      branch block.
AB  - The present case report describes the diagnosis of a concealed bypass tract in
      the right lateral wall revealed by electrophysiologic evaluation performed in a
      patient with rare palpitations. A iatrogenic right bundle branch block (RBBB)
      caused the occurrence of an incessant atrioventricular reentrant tachycardia. The
      disappearance of the RBBB determined a very difficult induction of the
      tachycardia that, when induced, showed a shorter cycle length and
      ventriculoatrial interval than those observed during RBBB tachycardia. The
      presence of a RBBB ipsilateral to the right free wall accessory pathway provided
      a critical delay within the circuit thus allowing the bypass tract to recover
      excitability. This relevant delay also allows the sinus beat to initiate and
      stabilize the tachycardia thus rendering it incessant.

PMID- 11453586
TI  - Myocardial perfusion and metabolic changes induced by biventricular pacing in
      dilated cardiomyopathy and left bundle branch block: description of a case
      evaluated by positron emission tomography.
AB  - The effects of biventricular pacing on myocardial wall function are well known,
      but, at the moment, its real effects on myocardial metabolism are unclear. In
      patients affected by left bundle branch block, at positron emission tomography a
      septal defect of the uptake of 18F-fluorodeoxyglucose (FDG) was referred. There
      were no alterations in myocardial perfusion, suggesting possible metabolic
      damage. In this paper we report the case of a patient affected by dilated
      cardiomyopathy and left bundle branch block treated with a biventricular device.
      Biventricular pacing resolved both the wall motion alterations as well as the
      defect in FDG uptake present in the septal area. On the contrary, during
      biventricular pacing there were no modifications in myocardial perfusion as
      compared to basal evaluation.

PMID- 11453587
TI  - Complex conotruncal heart defect, severe bleeding disorder and 22q11 deletion: a
      new case of Bernard-Soulier syndrome and of 22q11 deletion syndrome?
AB  - A patient with a deletion in the DiGeorge/velocardiofacial chromosomal region in
      22q11, underwent cardiac repair for truncus arteriosus with a separate origin of
      the pulmonary arteries. This patient presented with a severe coagulation disorder
      similar to that described in the Bernard-Soulier syndrome. Additional features
      included minor facial anomalies, transient hypocalcemia and renal failure. To the
      best of our knowledge, this is the third case of a severe bleeding disorder
      associated with 22q 11 deletion reported in the literature.

PMID- 11453588
TI  - Acute myocardial infarction caused by amphetamines: a case report and review of
      the literature.
AB  - Cardiotoxicity manifesting as myocardial ischemia is not generally recognized as
      a side effect of amphetamine use or abuse. However, at least 9 cases have been
      reported since 1987. In this report a case of acute myocardial infarction due to
      oral amphetamine therapy is presented. The patient was treated with thrombolytic
      therapy but there were no signs of reperfusion. His coronary cine-angiograms were
      normal. The literature regarding amphetamine use or abuse is also reviewed, and
      the possible mechanisms of this pathology are analyzed.

PMID- 11453589
TI  - Clinical characteristics and outcome of patients with invasive pneumococcal
      disease, Puy-de-Dome, France, 1994-1998.
AB  - A surveillance program for invasive pneumococcal disease was undertaken in Puyde
      Djme, an administrative district of the region Auvergne in France, from 1 January
      1994 to 31 December 1998. A total of 214 cases were identified. The annual
      incidence of invasive pneumococcal disease increased (P=0.04) from 5.5 in 1994 to
      9.3 cases per 10(5) person-years in 1998. The highest incidences were for
      children <2 years of age (59.2 cases per 10(5) person-years) and for adults > or
      = 65 years (18 cases per 10(5) person-years). Clinical diagnoses, available in
      200 patients, included acute pneumonia (62%), meningitis (10%), sepsis without
      focus (20%), and others (8%). The most frequent chronic medical conditions of the
      patients included smoking, alcoholism, cardiovascular and pulmonary diseases, and
      malignancies. Thirty-one percent of the isolates were nonsusceptible to
      penicillin. Penicillin resistance (MIC > or = 0.1 mg/l) was more frequent
      (P=0.02) in cancer patients. The overall case-fatality rate was 21.5%. Risk
      factors for death were age, sex, and underlying diseases of the patients, along
      with the severity of illness. These population-based findings should convince
      clinicians to offer pneumococcal vaccine to patients at high risk for invasive
      pneumococcal disease, thereby increasing vaccination coverage levels in France.

PMID- 11453590
TI  - Recovery from a single blood culture of two enterococcus gallinarum isolates
      carrying both vanC-1 and vanA cluster genes and differing in glycopeptide
      susceptibility.
AB  - Two Enterococcus gallinarum isolates distinguished by different colony sizes were
      recovered from the same blood culture from a woman with acute myeloid leukemia.
      They were designated E31 (the one with larger colonies) and E32 (the one with
      smaller colonies). Both isolates were glycopeptide resistant, but the MICs of
      vancomycin and teicoplanin for E31 (32 and 2 microg/ml, respectively, consistent
      with the VanC phenotype) and E32 (128 and 16 microg/ml, respectively, consistent
      with the VanA phenotype) were different. E31 and E32 had the same plasmid profile
      and showed identical pulsed-field gel electrophoresis patterns after digestion of
      total DNA with NotI and a two-band variation after digestion with SmaI.
      Polymerase chain reaction experiments showed that both isolates had both the vanC
      1 and vanA genes and carried a Tn1546-related transposon lacking orf1, vanY, and
      vanZ. The absence of these three genes was confirmed by Southern analysis with
      appropriate probes. Southern hybridization experiments using a vanA probe showed
      that this atypical Tn1546-related element appeared to be located on the
      chromosome. In both E31 and E32, the vanA probe hybridized to EcoRV and HindIII
      fragments larger in size than the hybridizing fragments observed in the VanA
      prototype strain Enterococcus faecium BM4147, suggesting the lack of the relevant
      EcoRV and HindIII restriction sites.

PMID- 11453591
TI  - Natural antibiotic susceptibility of recently established coryneform bacteria.
AB  - The natural susceptibility of 20 strains each of Brevibacterium casei (formerly
      CDC coryneform groups B-1 and B-3), Dermabacter hominis (formerly CDC coryneform
      groups 3 and 5), and Turicella otitidis (formerly coryneform group ANF-1-like)
      isolated from clinical specimens to 71 antibiotics was investigated.
      Susceptibility testing was carried out with a microdilution procedure using H
      medium. All three species were naturally sensitive to tetracyclines, most
      aminoglycosides, carbapenems, macrolides, lincosamides, glycopeptides, and
      rifampin. Susceptibility patterns indicating natural resistance to pipemidic
      acid, sulfamethoxazole, and cotrimoxazole also were found for all three species.
      Species-dependent discrepancies in susceptibility leading to completely different
      categorizations (changing from sensitive to resistant or vice versa) were found
      for some penicillins (e.g., oxacillin and amoxicillin), a few cephalosporins
      (e.g., ceftibutene), aztreonam, tobramycin, norfloxacin, fleroxacin,
      trimethoprim, nitrofurantoin, fosfomycin, and fusidic acid. For the majority of
      antibiotics, Brevibacterium casei was the least susceptible species and Turicella
      otitidis the most susceptible taxon. The present study describes a database on
      the natural susceptibility of Brevibacterium casei, Dermabacter hominis, and
      Turicella otitidis to a wide range of antibiotics. This database can be applied
      for the validation of susceptibility testing results of these recently
      established coryneform bacteria.

PMID- 11453592
TI  - Discordant prevalence of chlamydia trachomatis in asymptomatic couples screened
      using urine ligase chain reaction.
AB  - The following study was conducted to determine whether there would be an effect
      on the prevalence of Chlamydia trachomatis if both partners in a sexual
      relationship, rather than only one, underwent screening. First-void urine samples
      were collected from 1,690 asymptomatic women (mean age, 30 years; range, 15-70
      years) and their male sex partners (mean age, 33 years; range, 16-71 years). The
      duration of sexual partnership for these subjects ranged from 2 months to more
      than 10 years.. At the time of testing, 687 of the women were pregnant. Ligase
      chain reaction testing revealed that 42 (2.5%) female and 63 (3.7%) male urine
      samples were positive. Detection rates for Chlamydia trachomatis differed for
      males and females, a difference that was found to be significant (P<0.0046,
      McNemar chi-square). Both partners tested positive in 27 (1.6%) couples, whereas
      at least one partner tested positive in 78 (4.6%) couples. Thus, screening males
      for Chlamydia trachomatis would have identified 63 (81%) of these 78 couples
      compared with only 42 (54%) couples had females been screened exclusively. In
      standard clinical practice, women most often undergo screening. The results of
      this study underscore the need to screen both males and females for Chlamydia
      trachomatis.

PMID- 11453593
TI  - Characterization of isoniazid-resistant strains of Mycobacterium tuberculosis on
      the basis of phenotypic properties and mutations in katG.
AB  - Forty isoniazid-resistant Mycobacterium tuberculosis isolates were characterized
      on the basis of phenotypic properties (i.e., catalase activity, MIC of isoniazid,
      and growth pattern in the presence of 7 different concentrations of isoniazid)
      and alterations in the katG gene (codons 315 and 463). Three different growth
      patterns could be distinguished: concentration-dependent inhibition of growth was
      observed in 29 strains, similar growth at all concentrations was seen in 7
      strains, and enhanced growth at low concentrations of isoniazid was evident in 4
      strains. The MIC of isoniazid was < or = microg/ml for 29 of 40 strains. Mutation
      at codon 315 of the katG was detected in 28 of 40 strains. However, only one of
      the seven strains for which the MIC of isoniazid was > or = 16 microg/ml had
      mutation at this codon. Five of these seven strains for which the MIC was > or =
      16 microg/ml had no catalase activity. The results indicate that the MIC of
      isoniazid for a majority of strains is below the level achievable in serum.
      Therefore, isoniazid may be beneficial for the treatment of some cases of
      multidrug-resistant tuberculosis. Determination of catalase activity aids in the
      detection of isolates for which MICs are high and could, in conjunction with
      molecular methods, provide rapid detection of most isoniazid-resistant strains.

PMID- 11453594
TI  - Serotyping and antimicrobial susceptibility of group B Streptococcus over an
      eight-year period in southern Taiwan.
AB  - The increase in penicillin resistance among pneumococci and viridans streptococci
      and the development of serotype-specific conjugate vaccine have increased the
      need for knowledge of the antimicrobial susceptibility and the capsular serotypes
      of group B streptococci. Over an 8-year period, 351 group B streptococcal
      isolates from southern Taiwan were tested for antimicrobial susceptibility and
      serotype determination. Eighty-seven percent of the isolates were typeable. Types
      III (28.5%) and V (27.1%) were the most common serotypes. The occurrence of type
      V isolates increased with age, while that of type III isolates decreased with
      age, showing a predominance in children less than 1 year of age. Of 118 isolates
      from cases of invasive infection, types Ia, Ib, II, III, IV, and V accounted for
      12.7, 11.9, 0.8, 33, 1.7, and 26.3%, respectively. Using the agar dilution
      method, all isolates were found to be susceptible to penicillin, cefotaxime, and
      vancomycin, 99.4% to ofloxacin, 78.1% to chloramphenicol, 63.2% to azithromycin,
      62.6% to erythromycin, 57.3% to clindamycin, and 2.8% to tetracycline.
      Chloramphenicol resistance was associated with type III isolates (59 of 100, 59%)
      and erythromycin and azithromycin resistance with type Ib isolates (25 of 33
      176%], and 21 of 33 [64%], respectively). Thus, 72% of the isolates from invasive
      infections were serotype III, V, or Ia, and penicillin remains the drug of choice
      for treatment or prophylaxis of group B streptococcal infections in southern
      Taiwan, despite the high prevalence of penicillin resistance among Streptococcus
      pneumoniae and viridans streptococci.

PMID- 11453595
TI  - Prosthetic joint infection due to Veillonella dispar.
AB  - Described here is the first report of a monomicrobial joint infection caused by
      Veillonella dispar that resulted in loosening of a prosthesis. This clinical case
      shows that Veillonella spp. should not be disregarded as contaminant organisms,
      particularly when they are isolated in pure culture from clinical specimens
      involving cases of septic arthritis.

PMID- 11453596
TI  - Effect of iron limitation on slime production by Staphylococcus aureus.
AB  - The aim of this study was to examine the effect of growth conditions on slime
      production by Staphylococcus aureus clinical isolates. The addition of glucose to
      the medium enhanced slime production in the majority of Staphylococcus aureus
      isolates cultured from infections associated with orthopaedic prostheses. Iron
      limitation also stimulated this ability even in the absence of the additional
      carbohydrate source. Staphylococcus aureus isolates were classified as Group 1
      [strains producing slime only in trypticase soy broth supplemented with 1%
      glucose (TSBG) or in iron-limited trypticase soy broth (TSB/Fe-)]; Group 2 (slime
      + only in TSB/Fe-); or Group 3 (slime+ only in TSBG). Seven repeatedly slime
      negative strains were stimulated to produce slime by subpassaging in iron-limited
      medium. Low iron levels, usually found in vivo, could stimulate slime production
      by Staphylococcus aureus and support chronic infections associated with
      orthopaedic prostheses.

PMID- 11453597
TI  - Risk factors for esophageal candidiasis in a large cohort of HIV-infected
      patients treated with nucleoside analogues.
AB  - To assess the risk factors for esophageal candidiasis (EC), a cohort study and a
      case-control study were conducted using 1,368 French patients who were already
      participating in the Delta trial (which compared different types of
      antiretroviral therapy in HIV-infected patients) and who had no previous history
      of EC. During a median follow-up period of 19 months, 87 (6%) patients developed
      EC. The results of the cohort study showed an increased risk of EC associated
      with a low baseline CD4+ cell count (P<0.0001), a high baseline plasma HIV RNA
      level (P < 0.0001) and prior zidovudine therapy (P = 0.02) at entry to the study.
      The case-control study revealed an increased risk of EC in patients with a recent
      low CD4+ cell count (P < 0.0002), recent antibacterial chemotherapy (P = 0.01)
      and oral candidiasis (P < 0.05). Cotrimoxazole prophylaxis also increased the
      risk of EC (P = 0.04) in the case-control study.

PMID- 11453598
TI  - Phenotypical and genotypical characterization of Neisseria meningitidis carrier
      strains isolated from Polish recruits in 1998.
AB  - The aim of this study was to investigate the Neisseria meningitidis carriage rate
      among two cohorts of Polish recruits upon entry to the military and during the
      first 2 months of their service, i.e. in the spring and autumn of 1998, and to
      characterize the meningococcal strains isolated. Pharyngeal swabs were taken four
      and five times from 151 and 168 men, respectively. Altogether, 81 and 180
      meningococcal isolates representing 54 and 102 different strains were recovered.
      The overall rates of carriage in the spring and in the autumn were 36% and 61%,
      and, among recruits who submitted to sampling on at least three occasions, 39%
      and 55%. Eighty-three of 156 (53%) meningococcal carrier strains were
      nongroupable; among the remaining strains, serogroup B was predominant (32% of
      all carrier strains). In both surveys the predominant phenotype was Neisseria
      meningitidis NG:21:P1.7.

PMID- 11453599
TI  - Evidence of increased risk for leishmania infantum infection among HIV
      seronegative intravenous drug users from southern Spain.
AB  - To assess the prevalence of markers of Leishmania infection, 93 intravenous drug
      users and 77 nonusers of intravenous drugs underwent a Leishmania skin test and a
      serum Leishmania antibody search. All participants were human immunodeficiency
      virus seronegative. The Leishmania skin test was positive in 24 intravenous drug
      users and in 10 non-users of intravenous drugs (P=0.038). Leishmania
      seropositivity was detected in 3 of 11 active intravenous drug users and in 3 of
      82 former drug injectors (P=0.02). Positivity in the Leishmania skin test was
      associated with intravenous drug use (adjusted odds ratio, 2.33; 95% confidence
      interval, 1.03-5.24). The prevalence of Leishmania infection markers among
      intravenous drug users is higher than that among controls. This suggests that
      this parasite spreads through the sharing of needles.

PMID- 11453600
TI  - A case of disseminated aspergillosis with thyroid involvement.

PMID- 11453601
TI  - Salmonella lymphadenitis associated with undiagnosed lymphoma.

PMID- 11453602
TI  - A case of Q fever manifested solely as meningoencephalitis.

PMID- 11453603
TI  - Higher prevalence of antibodies to human herpesvirus 8 in HIV-infected
      individuals than in the general population in Ghana, West Africa.

PMID- 11453604
TI  - Alpha-fetoprotein and highly active antiretroviral therapy in patients coinfected
      with HIV-1 and hepatitis C virus.

PMID- 11453605
TI  - Commercial kits for yeast identification: concerns for standardisation.

PMID- 11453606
TI  - Physiologic changes in pregnancy and their effect on drug disposition.
AB  - Changes in maternal physiology occur normally during pregnancy and have the
      potential to alter the absorption, distribution, and elimination of drugs used
      therapeutically in pregnant women. These physiologic changes include: plasma
      volume expansion and increases in extracellular fluid space and total body water;
      decreased plasma albumin concentration; a compensated respiratory alkalosis;
      increased cardiac output with regional blood flow changes; increased renal blood
      flow associated with increased glomerular filtration; changes in hepatic drug
      metabolizing enzymes; and changes in gastrointestinal function. These changes
      begin in early gestation but are most pronounced in the third trimester of
      pregnancy. Further maternal physiologic changes occur intrapartum with some
      normalizing themselves within 24 hours of delivery, while others are sustained
      only returning to normal some 12 weeks postpartum. These physiologic changes form
      the basis for the need for pharmacokinetic studies during pregnancy.

PMID- 11453607
TI  - Approaches to pharmacokinetic/ pharmacodynamic modeling during pregnancy.
AB  - The modern approach in the field of pharmacokinetics/pharmacodynamics is the
      development of models based on the mechanisms of drug action and their alteration
      of physiologic processes. Such models often require consideration of the input
      and disposition kinetics of the drug, distribution to sites of action (biophase),
      processes controlling receptor binding or mediator turnover, mechanisms of drug
      activity, and signal transduction steps. Responses can often be categorized as:
      Direct (rapidly or slowly reversible), Indirect (inhibitory or stimulatory), or
      Irreversible. Further, there may be alterations in the system owing to tolerance,
      counter-regulation, pathophysiology, or physiological changes such as gender or
      pregnancy. Mathematical and computational tools are necessary for processing
      data. This article overviews many available pharmacodynamic models with an
      indication of the diverse approaches for quantitation of pharmacologic responses.
      Examples from the literature are illustrated with emphasis on changes occurring
      in kinetics and dynamics during pregnancy.

PMID- 11453608
TI  - The use of stable isotopes in drug metabolism studies.
AB  - Although there is a long history of stable isotopes use in drug metabolism
      research, it is appropriate to evaluate them in pregnancy drug studies in which
      safety takes highest priority. It is well established through a number of human
      and animal experiments that stable isotopes themselves rarely generate additional
      toxicities beyond the molecules to which they are attached. For the analysis of
      stable isotopes involved in metabolism studies, mass spectrometry plays the
      predominant role. Several mass spectrometry-based techniques now exist that
      enable the selective quantitative detection of stable isotopes with better
      sensitivity and better retention of chromatographic resolution than do in-line
      radioactivity monitors for 14C. Even mass balance studies can be performed by
      using stable isotopes, a type of experiment that still predominantly uses
      radioisotopes. Some of the newest developments in the use of stable isotopes
      involve biopolymers, in which fully isotope-labeled species can be generated from
      cells grown in isotopically labeled growth media. Having shown safety,
      sensitivity, specificity, and versatility, stable isotopes should play an
      important role in drug metabolism studies in pregnancy.

PMID- 11453609
TI  - Effects of pregnancy on specific diseases.
AB  - Of the numerous physiological changes associated with pregnancy that may have
      effects on various diseases, the marked increase in blood volume probably exerts
      the most pronounced effect. This increase may affect the serum level of many
      medications, as well as affecting various laboratory tests. Other important
      changes occur in the renal and hepatic system, which in turn may affect the
      clearance and metabolism of certain drugs and medications. Moreover, the response
      to and treatment of various diseases during pregnancy may be affected by the
      "attitude" of the health care providers who are often reluctant to perform
      certain diagnostic tests and procedures on the pregnant woman.

PMID- 11453610
TI  - The efficacy and safety of asthma medications during pregnancy.
AB  - Asthma may be the most common potentialy serious medical problem to complicate
      pregnancy. Because severe uncontrolled asthma may cause both maternal and fetal
      morbidity and mortality, pharmacological asthma therapy is often necessary during
      pregnancy. Only 1 published randomized controlled clinical trial has evaluated
      the efficacy of an asthma medication (inhaled beclomethasone) during pregnancy.
      Human data bearing on the safety of medications during pregnancy are usually
      limited to observational studies, because experimental studies on the use of
      medications during human pregnancy would generally be unethical. Existing
      observational cohort data do not associate an increased risk of preeclampsia,
      total congenital malformations, preterm birth, or low birth weight infants with
      maternal exposures to inhaled beta agonists, theophylline, cromolyn, or inhaled
      corticosteroids. Maternal use of oral corticosteroids has been associated with
      reduced birth weight, an increased risk of preeclampsia, and an increased risk of
      oral clefts (first trimester use). Based on this information, benefit-risk
      considerations suggest that inhaled asthma medications and theophylline should be
      used when indicated for the treatment of asthma during pregnancy. Moreover,
      although some increased risks may be associated with the gestational use of oral
      corticosteroids, these risks are probably still less than the potential risks to
      the mother and the fetus of severe uncontrolled asthma. This articles describes
      recently published consensus recommendations regarding the pharmacological
      management of asthma during pregnancy.

PMID- 11453611
TI  - The use of anticonvulsants during pregnancy.
AB  - Antiepilepsy (AED) medications have revolutionized the treatment of epilepsy,
      transforming it from a chronic progressive disease with inevitable cognitive and
      motor decline to a disorder in which most effected persons operate largely in a
      normal fashion. As with all medications adverse experiences can occur. However,
      it has been clear that the alternative of uncontrolled seizures are more
      hazardous than pharmacological therapies. However, physicians are faced with a
      dilemma when treating fertile or pregnant women with epilepsy. Many AED impair
      the effectiveness of oral contraceptives. There is evidence that some AED may
      effect fertility. AED metabolism changes in pregnancy, making management of women
      with epilepsy more difficult. AED exposure in early pregnancy increases the risk
      of congenital malformations, and exposure during other phases may increase the
      risk of developmental delay and neonatal hemorrhage. AED can be secreted in
      breast milk, thus extending the exposure into infancy. The exclusion of women of
      childbearing age from clinical trials limits our ability to collect information
      on the pharmacokinetics and potential adverse experiences of AED in pregnancy.
      Thus, when new medications are marketed, clinicians and their patients have no
      information on how to best manage conception, pregnancy, and lactation. This
      article discusses these issues in detail and describes our current understanding
      of the use of AED in women of childbearing age.

PMID- 11453612
TI  - Antihypertensive drugs during pregnancy.
AB  - Hypertensive disorders are the most common medical disorders during pregnancy.
      Their presence is associated with increased adverse maternal and fetal outcomes
      both acute and long-term. Antihypertensive agents are widely used in the
      treatment of these pregnancies despite absent evidence of either benefits or
      harms from this therapy. Multiple agents are available and various guidelines
      recommend different agents and various doses and regimens in the absence of
      information about the pharmacokinetics, disposition, and pharmacodynamic effects
      of these drugs in pregnancy. Randomized trials comparing antihypertensive therapy
      to a placebo are lacking and the available data have not shown clinical benefits
      because of inadequate sample size to rule out even moderate to large effects on
      perinatal outcome. In addition, data on teratogenic effects, adverse fetal
      neonatal effects, and long-term infant outcome are also scant. These problems
      resulted from lack of interest and support by the government and pharmaceutical
      companies to conduct research in pregnant women because of regulatory and medical
      legal concerns. Consequently, there is an urgent need to conduct clinical
      research in this area.

PMID- 11453613
TI  - Antithrombotic therapy during pregnancy.
AB  - Antithrombotic therapy is required during pregnancy for the prevention and
      treatment of venous and arterial thromboembolism and for the prevention of
      pregnancy loss in women at risk. The choice of anticoagulant for venous
      thromboembolism during pregnancy is limited to unfractionated heparin or low
      molecular weight heparin because the use of warfarin is relatively
      contraindicated. Much of the information surrounding the pharmacokinetics and
      dosing of unfractionated heparin and low molecular weight heparin obtained from
      non-pregnant patients has been applied to pregnant women. Whether this is
      appropriate in the presence of significant physiological changes in pregnancy is
      unclear. Specific to pregnancy and unfractionated heparin use, activated partial
      prothrombin time may be unreliable. In addition, the appropriate dosing of low
      molecular weight heparin is uncertain. Because venous thromboembolism can cause
      significant maternal morbidity and mortality, these important issues surrounding
      appropriate drug dosing of anticoagulants should be addressed.

PMID- 11453614
TI  - Design of antiretroviral clinical trials for HIV-1 infected pregnant women and
      their newborn infants.
AB  - Antiretroviral therapy has been highly successful in reducing mother to child
      transmission of human immunodeficiency virus-1 infection in pregnant women.
      However, the treatment regimens are intensive, difficult to deliver in less
      developed countries, and there are limited pharmacology studies addressing
      critical questions regarding maternal safety and fetal risk. There are currently
      3 pharmacologically diverse classes of antiretroviral agents with inadequate
      information available to define drug disposition necessary to determine
      appropriate dose regimens and limited data on long-term adverse events. This
      article summarizes representative clinical studies for selected antiretrovirals
      that provide a framework for continuing the necessary clinical research to extend
      successful outcomes in developed countries to human immunodeficiency virus-1
      infected pregnant women and infants world-wide and minimize the risk of long-term
      adverse effects.

PMID- 11453615
TI  - Antidepressants during pregnancy and lactation: defining exposure and treatment
      issues.
AB  - The majority of psychiatric illness onsets early in an individual's life,
      typically before or during the reproductive years. The increased incidence of
      major depression, dysthymia, and panic disorder in women compared with men
      underscores the likelihood that the clinician will encounter the clinical dilemma
      of medication use during pregnancy and lactation. The emergence of specialized
      clinics at several academic centers specifically to investigate and address
      issues in Perinatal psychiatry illustrates this conundrum best. The extant
      literature derived from human studies suggests that maternal mental illness and
      stress may have an adverse impact on obstetrical outcome. These clinical
      investigations are complemented by a burgeoning series of laboratory studies in
      rodents and nonhuman primates, showing the profound deleterious impact of
      maternal stress during the perinatal and neonatal periods on the development of
      the offspring. Data obtained from pharmaceutical registries, cohort studies,
      toxicology centers, and case series have consistently failed to show an adverse
      effect associated with in utero antidepressant exposure. Despite these advances
      and treatment guidelines proposed by the various academic leaders, investigations
      describing the extent of fetal/neonatal exposure, clinical methods for minimizing
      such exposure, and clinical treatment guidelines that include the physiological
      impact of pregnancy are sparse. The available literature shows distinct
      pharmacokinetic profiles of the selective serotonin reuptake inhibitors in
      placental passage and breast milk. Preliminary animal studies have shown higher
      than expected central nervous system concentrations associated with exposure
      during pregnancy and mathematical modelling for calculating infant exposure when
      nursing. The clinical import of these data will require further investigations of
      central nervous system bioavailability in the fetus and neonate.

PMID- 11453616
TI  - Difficulties in the study of adverse fetal and neonatal effects of drug therapy
      during pregnancy.
AB  - This article reviews the difficulties in studying adverse effects of drugs during
      pregnancy on the fetus and newborn. A study design should strive for prospective
      recording of drug intake during pregnancy, comparison to appropriate control
      groups adjusted for inherited traits, and single drug exposures for evaluation of
      specific syndromic causation, such as the Fetal Hydantoin Syndrome. Animal models
      are best used in mechanistic study of adverse drug effects on the fetus rather
      than for screening for adverse effects. Careful conclusions about causation of
      drug-induced adverse effects are needed to avoid false associations while
      providing appropriate safeguards to the fetus and newborn.

PMID- 11453617
TI  - Transplacental treatment of fetal tachycardia: implications of drug transporting
      proteins in placenta.
AB  - Sustained fetal tachyarrhythmia (> 180 bpm) is a potentially life-threatening
      condition for the unborn. Digoxin is commonly used as an initial monotherapy.
      Flecainide, sotalol, and verapamil are also used as a monotherapy or a
      combination therapy with digoxin. The treatment success rate with digoxin is
      about 50%. Presence of hydrops is associated with poor placental transfer of
      digoxin. Although transplacental pharmacotherapy has been available, it is a
      challenging task to maximize fetal drug exposure, while minimizing drug exposure
      of the mother. In addition, clear evidence behind drug of choice and treatment
      algorithm is lacking. Whereas prospective clinical studies with rigorous design
      remain to be seen, our knowledge on placental drug transport at a molecular level
      has been steadily increasing. For example, an ATP-dependent membrane protein,
      known as P-glycoprotein, is expressed in placenta, decreasing fetal exposure to
      maternal digoxin. Pharmacological manipulation of drug transporters may open a
      door to ultimate optimization of the transplacental pharmacotherapy.

PMID- 11453618
TI  - Response rate viewed as engagement bouts: effects of relative reinforcement and
      schedule type.
AB  - The rate of a reinforced response is conceptualized as a composite of engagement
      bouts (visits) and responding during visits. Part I of this paper describes a
      method for estimating the rate of visit initiations and the average number of
      responses per visit from log survivor plots: the proportion) of interresponse
      times (IRTs) longer than some elapsed time (log scale) plotted as a function of
      elapsed time. In Part 2 the method is applied to IRT distributions from rats that
      obtained food pellets by nose poking a lighted key under various multiple
      schedules of reinforcement. As expected, total response rate increased as a
      function of (a) increasing the rate of reinforcement (i.e., variable-interval
      [VI] 4 min vs. VI 1 mi), (b) increasing the amount of the reinforcer (one food
      pellet vs. four pellets), (c) increasing the percentage of reinforcers that were
      contingent on nose poking (25% vs. 100%), and (d) requiring additional responses
      after the end of the VI schedule (i.e., adding a tandem variable-ratio [VR] 9
      requirement). The first three of these variables (relative reinforcement)
      increased the visit-initiation rate. The tandem VR, in contrast, increased the
      number of responses per visit. Thus, variables that have similar effects on total
      response rate can be differentiated based on their effects on the componemts of
      response rate.

PMID- 11453619
TI  - Behavioral and pharmacological variables affecting risky choice in rats.
AB  - The effects of manipulations of response requirement, intertrial interval (ITI),
      and psychoactive drugs (ethanol, phencyclidine, and d-amphetamine) on lever
      choice under concurrent fixed-ratio schedules were investigated in rats.
      Responding on the "certain'' lever produced three 45-mg pellets, whereas
      responding on the "risky" lever produced either 15 pellets (p = .33) or no
      pellets (p .67). Rats earned all food during the session, which ended after 12
      forced trials and 93 choice trials or 90 min, whichever occurred first. When the
      response requirement was increased from 1 to 16 and the ITI was 20 s, percentage
      of risky choice was inversely related to fixed-ratio value. When only a single
      response was required but the ITI was manipulated between 20 and 120 s (with
      maximum session duration held constant), percentage of risky choice was directly
      related to length of the ITI. The effects of the drugs were investigated first at
      an ITI of 20 s, when risky choice was low for most rats, and then at an ITI of 80
      s, when risky choice was higher for most rats. Ethanol usually decreased risky
      choice. Phencyclidine did not usually affect risky choice when the ITI was 20 s
      but decreased it in half the rats when the ITI was 80 s. For d-amphetamine, the
      effects appeared to he related to baseline probability of risky choice; that is,
      low probabilities were increased and high probabilities were decreased. Although
      increase in risky choice as a function of the ITI is at variance with previous
      ITI data, it is consistent with foraging data showing that risk aversion
      decreases as food availability decreases. The pharmacological manipulations
      showed that drug effects on risky choice may be influenced by the baseline
      probability of risky choice, just as drug effects can be a function of baseline
      response rate.

PMID- 11453620
TI  - The general matching law describes choice on concurrent variable-interval
      schedules of wheel-running reinforcement.
AB  - Six male Wistar rats were exposed to concurrent variable-interval schedules of
      wheel-running reinforcement. The reinforcer associated with each alternative was
      the opportunity to run for 15 s, and the duration of the changeover delay was 1
      s. Results suggested that time allocation was more sensitive to relative
      reinforcement rate than was response allocation. For time allocation, the mean
      slopes and intercepts were 0.82 and 0.008, respectively. In contrast, for
      response allocation, mean slopes and intercepts were 0.60 and 0.03, respectively.
      Correction for low response rates and high rates of changing over, however,
      increased slopes for response allocation to about equal those for time
      allocation. The results of the present study suggest that the two-operant form of
      the matching law can be extended to wheel-running reinforcement. 'I'he effects of
      a low overall response rate, a short Changeover delay, and long postreinforcement
      pausing on the assessment of matching in the present study are discussed.

PMID- 11453621
TI  - Stimuli inevitably generated by behavior that avoids electric shock are
      inherently reinforcing.
AB  - A molecular analysis based on the termination of stimuli that are positively
      correlated with shock and the production of stimuli that are negatively
      correlated with shock provides a parsimonious count for both traditional discrete
      trial avoidance behavior and the data derived from more recent free-operant
      procedures. The necessary stimuli are provided by the intrinsic feedback
      generated by the subject's behavior, in addition to those presented by the
      experimenter. Moreover, all data compatible with the molar principle of shock
      frequency reduction as reinforcement are also compatible with a delay-of-shock
      gradient, but some data compatible with the delay gradient are not compatible
      with frequency reduction. The delay gradient corresponds to functions relating
      magnitude of behavioral effect to the time between conditional and unconditional
      stimuli, the time between conditioned and primary reinforcers, and the time
      between responses and positive reinforcers.

PMID- 11453622
TI  - Safe periods both explain and need explaining.

PMID- 11453623
TI  - Molar versus as a paradigm clash.
AB  - The molar view of behavior arose in response to the demonstrated inadequacy of
      explanations based on contiguity. Although Dinsmoor's (2001) modifications to two
      factor theory render it irrefutable, a more basic criticism arises when we see
      that the molar and molecular views differ paradigmatically. The molar view has
      proven more productive.

PMID- 11453624
TI  - Beyond the molar-molecular distinction: we need multiscaled analyses.
AB  - Dinsmoor's (2001) adherence to molecular analyses may require him to assert that
      molar and molecular principles are mutually exclusive, but to instead analyze the
      phenomena of avoidance as inherently multiscaled is to follow a well-established
      practice in the natural sciences. Besides the issue of scale, two-factor theory,
      which Dinsmoor advocates, has little to say about some important and longstanding
      results in experiments that qualify as avoidance.

PMID- 11453625
TI  - The molarity of molecular theory and the molecularity of molar theory.
AB  - Dinsmoor (2001) rejects shock-frequency reduction as a reinforcer for avoidance
      behavior, and considers this to be an invalidation of so-called molar avoidance
      theory. This is a narrow view of operant avoidance theory, for which shock
      frequency reduction is by no means the only reinforcer.

PMID- 11453626
TI  - Are responses in avoidance procedures "safety" signals?
AB  - Dinsmoor's (2001) position has the advantage of parsimony in that it relies on
      well-established principles rather than a separate process--shock-frequency
      reduction--to account for avoidance. Other advantages are that it blends well
      with what is known about the effectiveness of momentary contiguities in the study
      of positive reinforcement and that it might provide an account of why different
      response forms seem to condition at different rates. Despite these advantages,
      the view needs elaboration about the temporal characteristics of response
      associated stimuli, the functions that "warning'' stimuli may have, and
      especially about how ''safety" is established.

PMID- 11453627
TI  - A few minor suggestions.
AB  - We agree with almost all of the analysis in this excellent presentation of the
      molecular view of avoidance behavior. A few suggestions are made as follows:
      Referring to response-generated stimuli as ''readily observable" seems not quite
      right for the kinesthetic components of such stimuli, although their scientific
      legitimacy is not questioned. Interpreting response-generated stimuli as a form
      of positive reinforcement is contested, and an alternative interpretation is
      offered. A possibly simpler interpretation of the Sidman (1962) two-lever
      experiment is suggested. We question Dinsmoor's (2001) explanation for warning
      stimuli not being avoided, except for the reference to the weakness of third
      order conditioning effects. A final question is raised regarding the nature of
      the variables that are responsible for the momentary evocation of the avoidance
      response.

PMID- 11453628
TI  - Explaining avoidance: two factors are still better than one.
AB  - Two-factor theory remains a viable account of avoidance behavior. By emphasizing
      the interplay of respondent and operant contingencies, two-factor theory
      encourages the analysis of stimuli that mediate molar consequences and
      incorporates control by local events as well as events that are temporally
      remote, improbable, or cumulative.

PMID- 11453629
TI  - Two-factor theory has strong empirical evidence of validity.
AB  - Traditional two-factor theory is supported by parallels in the clinical
      literature. Theoretical problems with two-factor theory are obviated by the role
      of safety signals, which serve as positive conditioned reinforcers and retard the
      extinction of conditioned fear.

PMID- 11453630
TI  - The CYP P450 arachidonic acid monooxygenases: from cell signaling to blood
      pressure regulation.
AB  - The studies of the cytochrome P450 (P450) arachidonic acid (AA) monooxygenase,
      now established as a major pathway for the bioactivation of AA, have uncovered
      new and important functional roles for this enzyme system in cell and organ
      physiology, and in the metabolism of endogenous substrate. Past and present
      advances in P450 biochemistry and molecular biology are beginning to provide a
      description of the P450 isoform specificity of AA bioactivation, and the
      mechanisms of action and physiological relevance of the P450 metabolites.
      Associations between genetically controlled alterations in P450 function,
      expression, or regulation and functionally meaningful phenotypes point to the
      critical roles played by the AA monooxygenase in the control of systemic blood
      pressure and the pathophysiology of hypertension.

PMID- 11453631
TI  - Neutrophils, monocytes, and dendritic cells express the same specialized form of
      PSGL-1 as do skin-homing memory T cells: cutaneous lymphocyte antigen.
AB  - Memory T cells in inflamed skin express the cutaneous lymphocyte-associated
      antigen (CLA), a glycosylated epitope defined by the mAb HECA-452. We previously
      reported that on T cells, CLA occurs almost exclusively on the protein backbone
      of P-selectin glycoprotein ligand-1 (PSGL-1). T cells exhibiting the CLA isoform
      of PSGL-1 can tether and roll on both E- and P-selectin, while T cells expressing
      PSGL-1 without the CLA epitope do not bind E-selectin, though they may bind P
      selectin. We show here that circulating neutrophils and monocytes, and cultured
      blood dendritic cells, also express CLA almost entirely as an isoform of PSGL-1.
      These cells all tether and roll on both E- and P-selectin. A chimeric fusion
      protein incorporating the 19 N-terminal amino acids of mature PSGL-1 exhibited
      HECA-452 immunoreactivity and supported rolling of CHO cells expressing either E-
      or P-selectin. These findings indicate a site for the CLA modification within the
      distal tip of PSGL-1, previously shown to be critical for P-selectin binding and
      to mediate some, but not all, of the E-selectin binding of PSGL-1. We hypothesize
      that the types of circulating leukocytes discussed above all use CLA/PSGL-1 to
      tether and roll on E- and P-selectin along the vascular endothelium.

PMID- 11453632
TI  - Epicatechin is the primary bioavailable form of the procyanidin dimers B2 and B5
      after transfer across the small intestine.
AB  - Perfusion of isolated small intestine with the procyanidin dimers B2 and B5
      extracted from cocoa indicated that both forms of dimer are transferred to the
      serosal side of enterocytes but only to a very small extent (<1% of the total
      transferred flavanol-like compounds). However, perfusion of dimer mainly resulted
      in large amounts of unmetabolised/unconjugated epicatechin monomer being detected
      on the serosal side (95.8%). The cleavage of dimer during transfer seemed to be
      energy-dependent, requiring an intact cell system, as incubation with jejunal
      homogenates failed to yield epicatechin. Low levels methylated dimer were also
      detected (3.2%), but no conjugates and metabolites of epicatechin indicating that
      metabolism of monomer and dimer is limited during dimer cleavage/translocation.
      The methylation of dimer may be by catechol-O-methyltransferase, however, at high
      concentrations of dimer COMT activity is reduced leading to an inhibition of both
      monomer and dimer O-methylation.

PMID- 11453633
TI  - Restoration of abated T cell stimulation activity of mature dendritic cells.
AB  - Freshly isolated and cultured mature dendritic cells (DC) rapidly lose their high
      capacity to activate T cells. This diminished T cell activation activity is due,
      in part, to dramatically reduced expression of the costimulation ligands B7-1
      (CD80) and B7-2 (CD86). Here we show that cultivation of mature DC with the
      lymphokines TNFalpha, GM-CSF, or TNFalpha plus GM-CSF, fully restored and
      enhanced their T-cell stimulation activity by two to threefold, four to fivefold,
      or six to sevenfold, respectively. The restored T-cell stimulation activity was
      directly correlated with induced and increased levels of CD80 (16-fold) and CD86
      (10-fold) expression by the lymphokine-cultured DC. These results should
      facilitate many current DC-vaccination efforts towards generating more potent T
      cell responses.

PMID- 11453634
TI  - Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in
      acute starvation.
AB  - A number of acute wasting conditions are associated with an upregulation of the
      ubiquitin-proteasome system in skeletal muscle. Eicosapentaenoic acid (EPA) is
      effective in attenuating the increased protein catabolism in muscle in cancer
      cachexia, possibly due to inhibition of 15-hydroxyeicosatetraenoic acid (15-HETE)
      formation. To determine if a similar pathway is involved in other catabolic
      conditions, the effect of EPA on muscle protein degradation and activation of the
      ubiquitin-proteasome pathway has been determined during acute fasting in mice.
      When compared with a vehicle control group (olive oil) there was a significant
      decrease in proteolysis of the soleus muscles of mice treated with EPA after
      starvation for 24 h, together with an attenuation of the proteasome "chymotryptic
      like" enzyme activity and the induction of the expression of the 20S proteasome
      alpha-subunits, the 19S regulator and p42, an ATPase subunit of the 19S regulator
      in gastrocnemius muscle, and the ubiquitin-conjugating enzyme E2(14k). The effect
      was not shown with the related (n-3) fatty acid docosahexaenoic acid (DHA) or
      with linoleic acid. However, 2,3,5-trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone
      (CV-6504), an inhibitor of 5-, 12- and 15-lipoxygenases also attenuated muscle
      protein catabolism, proteasome "chymotryptic-like" enzyme activity and expression
      of proteasome 20S alpha-subunits in soleus muscles from acute fasted mice. These
      results suggest that protein catabolism in starvation and cancer cachexia is
      mediated through a common pathway, which is inhibited by EPA and is likely to
      involve a lipoxygenase metabolite as a signal transducer.

PMID- 11453635
TI  - Degradation of IkappaBalpha is limited by a postphosphorylation/ubiquitination
      event.
AB  - Regulation of IkappaBalpha during activation was examined using EGFP. Single cell
      analysis showed that both localisation- and cytokine-induced degradation of
      IkappaBalpha are dependent on expression levels. Cells expressing higher levels
      of the inhibitor demonstrated an increase in nuclear IkappaBalphaEGFP with a
      pronounced enhancement in the nuclear/cytoplasmic ratio. Enhancing the levels of
      the endogenous IkappaBalpha by relA transfection caused significant reduction in
      IL-1-mediated degradation of the fusion protein. Similarly, IkappaBalphaEGFP
      transfected cells showed an inverse correlation between the level of the fusion
      protein and IL-1-mediateddegradation. Comparing absolute levels demonstrated a
      biphasic response, with reduction in cells expressing over 15-fold that of
      endogenous levels. Further experiments using Western analysis showed a positive
      correlation between both phosphorylation and ubiquitination of IkappaBalphaEGFP,
      and the level the inhibitor. In contrast, and in agreement with the singlecell
      analysis, while IL-1 stimulation caused the expected degradation at lower levels
      of the fusion protein,breakdown of IkappaBalphaEGFP was totally inhibited at the
      higher transfection levels. The data show that turnover of IkappaBalpha is
      saturable and suggest that limitation of the pathway by enhanced inhibitor
      expression is regulated through a post phosphorylation/ubiquitination event, at
      the level of degradation.

PMID- 11453636
TI  - Investigation of the interaction among the components of the cytolethal
      distending toxin of Haemophilus ducreyi.
AB  - The cytolethal distending toxin (CDT) of Haemophilus ducreyi is encoded by the
      cdtABC genes, but the composition of active CDT is not known. Both immunoaffinity
      and metal affinity chromatographic methods were used to purify H. ducreyi CDT
      from recombinant Escherichia coli strains bearing wild-type or mutated H. ducreyi
      cdtABC genes. Both affinity-purified preparations contained CdtA, CdtB, and CdtC
      proteins. These purification efforts also revealed that the formation of a
      noncovalent CdtB-CdtC complex and production of a fully active CDT complex
      required the presence of a functional CdtA protein. When purified recombinant
      CdtB and CdtC proteins were mixed, only very slight CDT activity was detected. In
      contrast, when a bacterial cell extract containing CdtA was mixed with purified
      preparations of both CdtB and CdtC, full CDT activity was reconstituted in vitro.
      These results indicate that CdtA is essential for normal H. ducreyi CDT activity
      and that CdtA likely modifies or alters either CdtB or CdtC or both to form the
      active CDT complex.

PMID- 11453637
TI  - TBP-like protein (TLP/TLF/TRF2) artificially recruited to a promoter stimulates
      basal transcription in vivo.
AB  - Metazoan genomes generally contain one TBP-related gene designated as TBP-like
      protein (TLP/TLF/TRF2). Although TLP is thought to work for transcriptional
      regulation, its natural function has not been clearly demonstrated. Here we
      describe the stimulation of transcription from TATA-containing and TATA-less
      class II promoters by artificially recruited mammalian TLP. TLP fused with Gal4
      DNA-binding domain stimulated transcription when it was recruited at a proximal
      promoter. Compared to TBP, stimulation by TLP was less TATA-dependent. Slight
      truncation from each terminus of TLP destroyed this function drastically. Amino
      acid substitutions of TLP whose corresponding residues in TBP are crucial for its
      function resulted in the loss of function. Consequently, Gal4-fused TLP was
      demonstrated to exhibit ability of transcription activation irrespective of the
      type of promoter, the mechanism of which was thought to be similar to that of
      artificially recruited TBP. TLP is presumably able to behave as a transcriptional
      activator in cells.

PMID- 11453638
TI  - Nervous and nonnervous cell transduction by recombinant adenoviruses that
      inducibly express the human PrP.
AB  - The study of the prion protein (PrP) physiological functions or its specific role
      in transmissible spongiform encephalopathies (TSE) requires new tools,
      particularly those able to induce PrP overexpression in a large range of cells,
      in vivo as well as in vitro. Here we describe the construction of two recombinant
      adenoviruses encoding the human PrP either with a valine at position 129
      (AdTRVal) or a methionine (AdTRMet). Both genes were put under the control of the
      tetracycline-responsive promoter, allowing tight regulation of PrP expression.
      AdTRVal and AdTRMet induced high expression of the human PrP in CHO-KI cells and
      in organotypic brain slices in culture. The proteins expressed from these viruses
      exhibited a glycosylphosphatidyl inositol (GPI) anchor, proper glycosylation and
      sensitivity to proteinase K digestion. AdTRVal and AdTRMet will allow future
      studies on the human PrP and on the role of the codon 129 polyphormism in human
      TSE.

PMID- 11453639
TI  - Calmodulin-binding protein BP-10, a probable new member of plant nonspecific
      lipid transfer protein superfamily.
AB  - CaMBP-10 is a novel plant endogenous calmodulin-binding protein with important
      physiological functions. The partial cDNA sequence of this protein was cloned
      using RT-PCR. The deduced peptide (designated PCBP10) is composed of 74 amino
      acid residues containing a basic amphiphilic alpha-helix typical for calmodulin
      binding proteins. PCBP10 shows very high amino acid sequence homology with plant
      nonspecific lipid-transfer proteins (nsLTPs). Sequence analysis also reveals that
      PCBP10 has similar amino acid composition to plant nsLTPs, and seven of the eight
      conserved cysteine residues are found in PCBP10. Furthermore, the secondary
      structure features of PCBP10 are very similar to those of plant nsLTPs. In
      addition, there are striking resemblances between CaMBP-10 and plant nsLTPs in
      their biochemical and physical properties. Our results suggest that CaMBP-10 is a
      novel member of the plant and nsLTP gene family, and the Ca(2+)/CaM regulative
      system may also play roles in lipid metabolism, defense reactions, and the
      adaptation of plants to natural environment.

PMID- 11453640
TI  - Formation of HIV-1 envelope-hepatitis B core antigen hybrids with high affinity
      for CD4.
AB  - We have identified an acceptor site on HIV gp120, where foreign protein sequences
      can be inserted while retaining the native conformation of gp120. The resulting
      hybrids showed dual antigenicity, normal glycosylation, and high affinity binding
      of the CD4 receptor. This site allows insertion of highly immunogenic proteins
      such as core antigen of hepatitis B virus. By combining the immunogenicity of the
      carrier protein with the antigenicity of gp120, these hybrids may lead to
      modified HIV-1 antigens with enhanced immunogenicity.

PMID- 11453641
TI  - Liver alcohol dehydrogenase is degraded by the ubiquitin-proteasome pathway.
AB  - Dihydrotestosterone (DHT) decreases rat liver alcohol dehydrogenase (ADH) due
      principally to an increased rate of degradation of the enzyme. The pathway of
      degradation of ADH was investigated. Exposure of hepatocytes in culture to
      lactacystin or to MG132, which are inhibitors of the ubiquitin-proteasome pathway
      of protein degradation, resulted in higher ADH. Furthermore, both lactacystin and
      MG132 prevented the decrease in ADH caused by DHT. By contrast, the lysosomal
      proteolytic inhibitors 3-methyladenine and leupeptin as well as inhibitors of the
      calcium-activated neutral protease calpain system had no effect on ADH in the
      absence or presence of DHT. ADH isolated by immunoprecipitation from hepatocytes
      exposed to DHT reacted specifically with anti-ubiquitin antibody. Ubiquitinated
      ADH was also demonstrated in hepatocytes exposed to MG132. The combination of DHT
      and MG132 resulted in more ubiquitinated ADH than exposure to either compound
      alone. These results suggest that the ubiquitin-proteasome pathway plays a role
      in the degradation of ADH and in the enhanced degradation of this enzyme by DHT.

PMID- 11453642
TI  - Targeting elements in the amino-terminal part direct the human 70-kDa peroxisomal
      integral membrane protein (PMP70) to peroxisomes.
AB  - Peroxisomes are multipurpose organelles present in nearly all eukaryotic cells.
      All peroxisomale matrix and membrane proteins are synthesized in the cytoplasm.
      While a clear picture of the basic targeting mechanisms for peroxisomal matrix
      proteins has emerged over the past years, the targeting processes for peroxisomal
      membrane proteins are poorly understood. The 70-kDa peroxisomal integral membrane
      protein (PMP70) is one of the proteins located in the human peroxisome membrane.
      PMP70 belongs to the family of ATP-binding cassette (ABC) transporter proteins.
      It consists of six transmembrane domains and an ATP-binding fold in the cytosol.
      Here we describe that efficient peroxisomal targeting of human PMP70 depends on
      three targeting elements in the amino-terminal protein region, namely amino acids
      61 to 80 located in the cytosol as well as the first and second transmembrane
      domains. Furthermore, peroxin 19 (PEX19) interactions are not required for
      targeting human PMP70 to peroxisomes. PEX19 does not specifically bind to the
      targeting elements of human PMP70.

PMID- 11453643
TI  - Involvement of p38 MAP kinase pathway in the synergistic activation of PACAP mRNA
      expression by NGF and PACAP in PC12h cells.
AB  - We have recently shown that in PC12 cells, PACAP and NGF synergistically increase
      PACAP gene transcription and mRNA level, and that the MAPK/ERK kinase inhibitor
      PD98059 blocks the PACAP mRNA expression induced by either PACAP or NGF, but not
      that induced by the combination, suggesting involvement of multiple signaling
      pathways. Here we show that the p38 MAPK inhibitor SB203580 almost completely
      inhibits the PACAP mRNA expression induced by PACAP alone or in combination with
      NGF. PACAP induces neurite outgrowth and potentiates NGF-induced neurite
      outgrowth in PC12h cells. Unlike the case for the PACAP mRNA expression, SB203580
      did not affect, but PD98059 reduced, PACAP and NGF-induced neurite outgrowth.
      These results indicate that PACAP receptors are coupled to the p38 signaling
      pathway, and that p38 plays a key role in the regulation of PACAP gene
      expression, while ERK, but not p38, MAPK is involved in PACAP and NGF-induced
      neurite outgrowth.

PMID- 11453644
TI  - Evidence for cadmium uptake through Nramp2: metal speciation studies with Caco-2
      cells.
AB  - The specific uptake of 0.3 microM (109)Cd by the TC7 clone of the human
      enterocytic-like Caco-2 cells increased 4-fold as the pH(out) was lowered from
      7.5 to 5.5; the stimulatory effect of acidic media being more pronounced when the
      level of the free ion (109)Cd(2+), relative to total (109)Cd, was increased. The
      initial uptake rate was 12-fold higher under conditions, optimizing (109)Cd(2+)
      accumulation over that of (109)CdCl(2-n)(n) (NO(-)(3)/pH(out) 5.5); a saturable
      system of transport has been characterized (K(m) = 1.1 +/- 0.1 microM, V(max) =
      87 +/- 3 pmol/3 min/mg protein). An excess of Fe(2+) failed to affect (109)Cd
      uptake when the pH(out) was 7.4, whereas a strong inhibition was observed under
      NO(-)(3)/pH(out) 5.5 conditions. In contrast, the maximal inhibitory effect of
      Zn(2+) was observed under Cl(-)/pH(out) 7.4 conditions. This results strongly
      suggest that Fe(2+) may compete with Cd(2+) for Nramp2, whereas Zn and CdCl(2
      n)(n) compete for another system of transport that has yet to be identified.

PMID- 11453645
TI  - Reactive oxygen and NF-kappaB in VEGF-induced migration of human vascular smooth
      muscle cells.
AB  - Migration and proliferation of vascular smooth muscle cells (VSMC) contribute to
      angiogenesis and the lesions of atherosclerosis. Since, vascular endothelial
      growth factor (VEGF) is overexpressed by VSMC in intima of atherosclerotic human
      coronary arteries, we determined if VEGF could stimulate VSMC migration and the
      intracellular signals involved. VEGF induced VSMC migration but had no
      significant activity on proliferation. VEGF increased intracellular reactive
      oxygen species (ROS), NF-kappaB activation and IL-6 expression. Blockade of the
      generation of intracellular ROS by antioxidants inhibited VEGF-induced NF-kappaB
      activation, IL-6 expression, and cell migration indicating that generation of ROS
      was required for NF-kappaB activation and the chemotactic activity of VEGF.
      Expression of a mutated, nondegradable form of inhibitor of NF-kappaB (IkappaB
      alphaM) suppressed VEGF-triggered activation of NF-kappaB and upregulation of IL
      6 as well as VSMC migration. Neutralization of IL-6 by its antibody significantly
      attenuated the migration stimulated by VEGF. Collectively, our data provide the
      first evidence that intracellular ROS and NF-kappaB are required for VEGF
      mediated smooth muscle cell migration. Further, IL-6 induced by VEGF is involved
      in the ability of the growth factor to stimulate migration.

PMID- 11453646
TI  - Rac is activated by tumor necrosis factor alpha and is involved in activation of
      Erk.
AB  - Tumor necrosis factor alpha (TNFalpha) activates various signal transduction
      pathways including those involving phosphatidylinositol 3-kinase (PI3K),
      extracellular signal-regulated kinases (Erk), c-Jun N-terminal protein kinases
      (JNK), and p38 kinases. Using the Rac binding domain of PAK (PAK-RBD) as an
      activation-specific probe, here we demonstrate that TNFalpha very rapidly and
      transiently activates the Rho family GTPase Rac in L929 cells. The PI3K inhibitor
      LY294002 significantly inhibited TNFalpha activation of Rac as well as Erk and
      abolished that of the PI3K target Akt, without showing any inhibitory effects on
      JNK and p38 activation. Furthermore, TNFalpha activation of Erk was abolished by
      a dominant negative Rac mutant, Rac17N, or by an activated Rac mutant, Rac12V.
      These findings suggest that Rac is activated by a mechanism that is at least
      partly dependent on PI3K in TNFalpha stimulated cells and plays a critical role
      in activation of the Erk signaling pathway.

PMID- 11453647
TI  - Zinc enhances synthesis of presenilin 1 in mouse primary cortical culture.
AB  - Whether zinc interacts with presenilin 1 (PS1), one of the causative genes of
      familial Alzheimer's disease (AD), is not known. Here we report that zinc
      modulates the synthesis of PS1. Exogenous zinc enhanced the amount of C-terminal
      fragments of PS1 (PS1-CTF) in neonatal mouse cortical cultures in a dose
      dependent manner. Zinc also induced cell death in a dose-dependent manner. These
      effects of zinc were not mimicked by calcium, copper, or iron, and were blocked
      by a zinc-specific chelator, TPEN. Experiments using metabolic labeling and
      cycloheximide treatment revealed that zinc increased PS1-CTF by elevating the de
      novo synthesis of PS1. Time course experiments revealed that cell death commenced
      sooner (0.5-1 h) than enhancement of PS1-CTF (1-2 h) following zinc treatment.
      However, the amount of PS1-CTF remained unchanged during etoposide- or H(2)O(2)
      induced cell death, suggesting that enhancement of PS1 synthesis is specifically
      correlated with zinc-induced cell death.

PMID- 11453648
TI  - Aggretin, a C-type lectin protein, induces platelet aggregation via integrin
      alpha(2)beta(1) and GPIb in a phosphatidylinositol 3-kinase independent pathway.
AB  - Aggretin purified from Calloselasma rhodostoma venom was previously identified as
      alpha(2)beta(1) agonist in triggering platelet aggregation, and exists as a
      heterodimer sharing a great homologous sequence to GPIb binding proteins. We show
      here that binding to GPIb is also required in aggregation-inducing activity of
      aggretin. A2-IIE10, an anti-integrin alpha(2) monoclonal antibody, delayed
      platelet aggregation while agkistin, a GPIb antagonist, only slightly inhibited
      platelet aggregation caused by aggretin. However, the aggretin-induced platelet
      aggregation was completely abolished by a combination of A2-IIE10 and agkistin.
      Either A2-IIE10 or agkistin significantly inhibited the binding of FITC-aggretin
      toward fixed platelets. Aggretin and collagen induced a similar signal
      transduction in platelets involving a time-dependent tyrosine phosphorylation of
      p125(FAK) and PLCgamma2, but aggretin caused a much-delayed tyrosine
      phosphorylation of PI 3-kinase compared with collagen. LY294002, a PI 3-kinase
      inhibitor, showed a significant inhibitory effect on collagen, but not aggretin
      stimulated platelet aggregation. These findings indicate aggretin induces
      platelet aggregation via binding of alpha(2)beta(1) and GPIb, causing
      phosphorylation of p125(FAK) and PLCgamma2 leading to platelet activation without
      the involvement of PI 3-kinase activation.

PMID- 11453649
TI  - A novel domain of the yeast heat shock factor that regulates its activation
      function.
AB  - Heat shock factor Hsf1 of the yeast Saccharomyces cerevisiae binds to the heat
      shock element (HSE) of a subset of genes and activates their transcription in
      response to various environmental stresses. Hsf1 protein contains discrete
      domains respectively involved in DNA-binding, trimerization, transcription
      activation, and transcription repression. Here we have identified a novel domain
      rich in basic amino acids at the extreme C-terminus of Hsf1. Deletion or point
      mutations of the C-terminal basic region caused an inefficient heat shock
      response of genes containing noncanonical HSEs such as CUP1 and HSP26. The basic
      region is also essential for oxidative stress-inducible transcription of CUP1 by
      Hsf1. By contrast, it was dispensable for heat induction through the canonical
      HSE. We suggest that the basic region is a modulator involved in regulation of
      the Hsf1-mediated activation depending on the architecture of its binding site.

PMID- 11453650
TI  - Kinetics study of a selenium-containing ScFv catalytic antibody that mimics
      glutathione peroxidase.
AB  - The steady state kinetic study and some enzymic characterization of a selenium
      containing scFv catalytic antibody (Se-scFv2F3) was carried out. A novel reaction
      formula of this abzyme-catalyzed reaction was proposed and a rate equation was
      gotten according to the formula. The constants in the equation were compared with
      Dalziel's parameters and the exact meanings of these constants were analyzed. The
      gotten kinetics parameters from the kinetics study of Se-scFv2F3 were analyzed
      and compared with that of native glutathione peroxidase.

PMID- 11453651
TI  - Carboxyl-methylation of Rab3D in the rat pancreatic acinar tumor cell line AR42J.
AB  - Rab3D is a small GTPase implicated in regulated exocytosis, and is a marker of
      secretory granules in exocrine cells. We have previously shown that rab3D
      undergoes reversible carboxyl-methylation in adult rat pancreatic acinar cells,
      and that carboxyl-methylation of rab3D is developmentally regulated concomitantly
      with the maturation of the regulated secretory apparatus in rat pancreas. We also
      observed that dexamethasone treatment of the rat pancreatic acinar tumor cell
      line, AR42J, led to a significant increase in the size of the unmethylated pool
      of a rab3-like protein. The current study was designed to further characterize
      this rab3-like protein. Here we show that AR42J cells express rab3D, and that the
      protein focuses on 2D gels as two spots with pI values of 4.9 and 5.0. Treatment
      of AR42J cells with N-acetyl-S-geranylgeranyl-l-cysteine, an inhibitor of
      carboxyl-methylation, led to a decrease in the basic form of rab3D and a
      proportional increase in the acidic form. In contrast, N-acetyl-S-farnesyl-l
      cysteine, which inhibits carboxyl-methylation of farnesylated proteins, had no
      effect. Lovastatin, an inhibitor of geranylgeranylation, also induced an
      accumulation of the acidic form of rab3D. Taken together, these data indicate
      that rab3D can undergo reversible carboxyl-methylation in AR42J cells by a
      geranylgeranyl-specific methyltransferase. The 2D gel and immunoblotting analyses
      indicated that dexamethasone treatment of AR42J cells led to an increase in the
      proportion of the unmethylated form of rab3D concurrent to inducing a regulated
      secretory pathway, similar to the rab3D profile change in developing rat
      pancreas. Our data, along with previous studies done on developing rat pancreas,
      indicate that the tumor cell line AR42J represents a good model system for
      studying the regulated secretory pathway, and that carboxyl-methylation of rab3D
      may play a role in the acquisition of stimulus-secretion coupling.

PMID- 11453652
TI  - Identification of a novel human ankyrin-repeated protein homologous to CARP.
AB  - We cloned a novel ankyrin repeat protein, Arpp, by immunoscreening a cDNA library
      constructed from a human esophageal carcinoma cell line, TE1, with an antibody
      directed to a hypothetical protein encoded by antisense p53 mRNA. Arpp protein is
      composed of 333 amino acids and contains four ankyrin-like repeat motifs in the
      middle portion of the protein, a PEST-like sequence and a lysine-rich sequence
      similar to a nuclear localization signal in the N-terminal region, and a proline
      rich region containing consensus phosphorylation sites in the C-terminal region.
      Protein sequence analysis revealed that Arpp is homologous (52.7% identity) to
      Carp which is shown to be involved in the regulation of the transcription of the
      cardiac ventricular myosin light chain 2 gene. Arpp mRNA was found to be
      expressed in normal skeletal and cardiac muscle. Interestingly, Arpp expression
      was detectable in bilateral ventricles, but undetectable in bilateral atria and
      large vessels, suggesting that Arpp may play a specific function in cardiac
      ventricles as well as skeletal muscles.

PMID- 11453653
TI  - Ultra rapid calcium events in electrically stimulated frog nerve terminals.
AB  - Fast calcium events occurring in cytoplasmic organelles after a single electrical
      stimulus were investigated by electron spectroscopic imaging (an electron
      microscope technique that reveals total calcium with high sensitivity and spatial
      resolution) in quick frozen presynaptic terminals of the frog neuromuscular
      junction. In resting preparations synaptic vesicles showed a prominent calcium
      signal whereas mitochondria were mostly negative and only some of the cisternae
      of the endoplasmic reticulum were clearly positive. In preparations quick frozen
      10 ms after the application to the nerve of a single, supramaximal electric
      stimulus, no obvious change was observed in synaptic vesicles, while calcium
      levels rose to high values in the endoplasmic reticulum cisternae and in the
      matrix of mitochondria. Voltage-induced influx of Ca(2+) within synaptic
      terminals appears therefore to induce an extremely rapid uptake into selected
      organelles. The possible physiological role of this response is discussed.

PMID- 11453654
TI  - Marked reduction of Helicobacter pylori-induced gastritis by urease inhibitors,
      acetohydroxamic acid and flurofamide, in Mongolian gerbils.
AB  - Urease has been suggested to be essential for colonization and pathogenesis of
      Helicobacter pylori infection. In the present study, we evaluated the effects of
      urease inhibitors [acetohydroxamic acid (AHA) and flurofamide (FFA)] on H. pylori
      induced gastritis in Mongolian gerbils. Animals were orally inoculated with H.
      pylori, and given urease inhibitors in their diet throughout the experimental
      period of six weeks or four weeks, starting from two weeks after H. pylori
      inoculation. With the administration of AHA at doses of 100, 500, and 2500 ppm
      throughout the experimental period, H. pylori-induced gastritis in animals was
      decreased in a dose-dependent manner, significantly so at 2500 ppm. Suppression
      of gastric lesions was also evident in animals administered 2500 ppm AHA after
      the H. pylori infection. Bacterial infection rates were reduced to 40-50% of the
      control value of 100%, by the highest dose of AHA. The potent urease inhibitor,
      FFA, also caused marked amelioration of H. pylori-associated gastritis on
      administration at 100 ppm throughout the six-week experimental period or for four
      weeks after H. pylori infection. Animals treated with FFA had few visible gastric
      lesions, and the proportion infected with H. pylori was reduced to less than 10%.
      Since antibiotic-resistant strains of H. pylori have become a serious problem,
      nonantibiotic urease inhibitors may be very useful to control H. pylori
      associated gastroduodenal disease.

PMID- 11453655
TI  - Sequence features and evolutionary mechanisms in the chicken avidin gene family.
AB  - The chicken avidin gene family comprises the avidin gene (avd) and several
      homologous avidin-related genes (avrs). The sequences of the avr genes are nearly
      identical to each other but exhibit nonrandomly distributed, frequently
      nonsynonymous nucleotide substitutions compared to avd. In this study, we
      determined the genetic distances and the phylogeny of the avd and avr genes and
      found differences between different exons and introns. Our results suggest the
      involvement of biased gene conversion in the evolution of the genes. Furthermore,
      one of the genes was identified as a putative fusion gene. The occurrence of both
      gene conversion and recombination supports the models suggesting a common
      initiation mechanism for conversion and crossing-over. The existence of avidin
      related proteins (AVRs) is currently unknown, but the putative AVRs are expected
      to bind biotin similarly to avidin. However, the observed sequence differences
      may affect the stability and glycosylation patterns of the putative AVR proteins.

PMID- 11453656
TI  - Production and characterization of an antiserum which recognizes the native
      receptor for thyrotropin-releasing hormone.
AB  - Despite attempts in several laboratories, it has been difficult to prepare
      antiserum to the thyrotropin-releasing hormone receptor (TRHR). We have prepared
      a polyclonal anti-rat TRHR antiserum by immunization of rabbits with a synthetic
      peptide corresponding to the C-terminus of the TRHR. The specificity of the
      antiserum was assessed by enzyme-linked immunosorbent assay. The affinity
      purified antibody recognized a major broad band at 50-60 kDa and a minor broad
      band at 100-120 kDa in Western blot analysis of membrane proteins from TRHR
      transfected, but not control, HEK293t cells. Binding to both bands was abolished
      by preincubation with the immunizing peptide but not control peptide. The
      approach was repeated with rat pituitary F4C1 cells, which lack endogenous TRHRs;
      membranes from F4C1 cells transfected with TRHR cDNA, but not control cells,
      showed specific binding by Western blot. Using laser confocal microscopy, the
      TRHR was visualized on the plasma membrane of transfected, but not control, F4C1
      cells. Similar confocal findings were observed in TRHR-transfected HEK293t cells.
      Within 5 min after TRH addition, the TRHR signal translocated from the plasma
      membrane to the cytoplasm of F4C1 cells transfected with TRHR cDNA. Ten minutes
      after TRH addition, the TRHR signal formed aggregates in the cytoplasm. Thirty
      minutes after TRH treatment, both cytoplasmic and plasma membrane localizations
      were observed, suggesting recycling of some TRHRs back to the plasma membrane.
      These observations are consistent with our previous findings using an epitope
      tagged TRHR. In conclusion, we have prepared an antiserum that recognizes the
      native TRHR by Western blot analysis and confocal microscopy.

PMID- 11453657
TI  - Effects of flow patterns on endothelial cell migration into a zone of mechanical
      denudation.
AB  - Vascular endothelial cells (ECs) in vivo are subject to different flow conditions
      due to the variation in vessel geometry. The aim of this study is to elucidate
      the effects of different flow conditions on EC monolayer migration into a
      mechanically denuded zone and their underlying mechanisms. Both laminar and
      disturbed flows significantly enhanced EC migration. EC migration speed was the
      fastest under laminar flow, which preferentially promoted directional EC
      migration from the upstream side of the wounded monolayer. C3 exoenzyme (a Rho
      inhibitor) inhibited EC migration under static and flow conditions, and markedly
      reduced the effects of flow on EC migration. These results indicate that flow
      promotes EC migration through the Rho signaling pathway. Genistein (a tyrosine
      kinase inhibitor) selectively retarded EC migration under disturbed flow,
      suggesting that tyrosine phosphorylation may play a role in EC migration under
      disturbed flow. This study has demonstrated that different flow patterns
      differentially affect EC monolayer migration into the denuded zone involving
      multiple mechanisms.

PMID- 11453658
TI  - Cloning and functional characterization of DSCAML1, a novel DSCAM-like cell
      adhesion molecule that mediates homophilic intercellular adhesion.
AB  - DSCAM, a conserved gene involved in neuronal differentiation, is a member of the
      Ig superfamily of cell adhesion molecules. Herein, we report the functional
      characterization of a human DSCAM (Down syndrome cell adhesion molecule)
      paralogue, DSCAML1, located on chromosome 11q23. The deduced DSCAML1 protein
      contains 10 Ig domains, six fibronectin-III domains, and an intracellular domain,
      all of which are structurally identical to DSCAM. When compared to DSCAM, DSCAML1
      protein showed 64% identity to the extracellular domain and 45% identity to the
      cytoplasmic domain. In the mouse brain, DSCAML1 is predominantly expressed in
      Purkinje cells of the cerebellum, granule cells of the dentate gyrus, and in
      neurons of the cerebral cortex and olfactory bulb. Biochemical and
      immunofluorescence analyses indicated that DSCAML1 is a cell surface molecule
      that targets axonal features in differentiated PC12 cells. DSCAML1 exhibits
      homophilic binding activity that does not require divalent cations. Based on its
      structural and functional properties and similarities to DSCAM, we suggest that
      DSCAML1 may be involved in formation and maintenance of neural networks. The
      chromosomal locus for DSCAML1 makes it an ideal candidate for neuronal disorders
      (such as Gilles de la Tourette and Jacobsen syndromes) that have been mapped on
      11q23.

PMID- 11453659
TI  - BMP-7-induced cell cycle arrest of anaplastic thyroid carcinoma cells via
      p21(CIP1) and p27(KIP1).
AB  - The aim of the present study was to investigate the effect of bone morphogenetic
      protein (BMP-7) on thyroid carcinoma cell growth. Addition of BMP-7 inhibited the
      proliferation of four out of six human anaplastic thyroid carcinoma cell lines,
      observed as decreased incorporation of (3)H-thymidine and decreased cell number.
      The growth inhibitory effect was cell density-dependent; sparse cells were
      inhibited by BMP-7 whereas dense cells were not. Cell cycle analysis by flow
      cytometry showed an increased fraction of cells in the G1-phase and subsequent
      decrease in both S- and G2/M-phase after BMP-7 stimulation. Furthermore, BMP-7
      caused an upregulation of the cyclin-dependent kinase inhibitors (CDKIs) p21 and
      p27, decreased activity of Cdk2 and Cdk6, and hypophosphorylation of the
      retinoblastoma protein (pRb). These findings suggest a growth inhibitory effect
      of BMP-7 on anaplastic thyroid carcinoma cells by inhibition of Cdk activity
      shifting the Rb protein to the hypophosphorylated state.

PMID- 11453660
TI  - Epicatechin selectively prevents nitration but not oxidation reactions of
      peroxynitrite.
AB  - The flavanol (-)-epicatechin has been found to protect against damage inflicted
      by peroxynitrite, an inflammatory intermediate. Here, epicatechin was tested in
      systems of increasing complexity. The compound efficiently protected against
      nitration of protein tyrosine residues by peroxynitrite (IC(50) approximately
      0.02 mol epicatechin/mol peroxynitrite). However, at epicatechin concentrations
      completely preventing nitration of tyrosine by peroxynitrite, protection against
      the oxidative inactivation of glyceraldehyde-3-phosphate dehydrogenase or soybean
      lipoxygenase-1 was marginal (IC(50) > 1 mol epicatechin/mol peroxynitrite),
      approximately two orders of magnitude less. Likewise, epicatechin was relatively
      ineffective against oxidation of thiols in cell lysates, and against the
      oxidation of 2',7'-dichlorodihydrofluorescein in cultured cells. The activation
      of the kinases Akt/protein kinase B, ERK1/2 and p38-MAPK by peroxynitrite in
      murine aorta endothelial cells was not altered by epicatechin, suggesting that
      activation of these kinases is due to processes other than tyrosine nitration.

PMID- 11453661
TI  - Association of MUC-1 and SPGL-1 with low-density microdomain in T-lymphocytes: a
      preliminary note.
AB  - Two mucin-type glycoproteins, MUC-1 and P-selectin glycoprotein ligand-1 (PSGL
      1), and glycosphingolipids (GSLs), expressed in human T-cell line HUT78, were
      highly enriched in low-density buoyant fraction (termed "GEM"), together with
      CD45, Yes, Fyn, and lck(56). Enrichment of MUC-1, PSGL-1 and GSLs, together with
      these signal transducer molecules in low-density membrane fraction was observable
      when fraction was prepared from cells either in nonionic detergent Brij 58 or in
      hypertonic alkaline conditions (500 mM Na(2)CO(3)). On pretreatment of cells with
      cholesterol-binding reagent methyl beta-cyclodextrin, levels of MUC-1 and PSGL-1
      together with the above signal transducers in GEM was greatly reduced, and they
      were translocated into high-density membrane fraction. Similar association of
      lck(56), Yes, Fyn, and cSrc together with MUC-1 was also found in GEM fraction of
      mouse T-cell lymphoma EL4 cells expressing MUC-1 through transfection of its
      gene. These findings indicate the presence of another glycosyl cluster
      ("glycocluster"), in addition to the previously well-established GSL cluster
      organized with signal transducer molecules in GEM fraction, and its possible
      functional role in T-cells.

PMID- 11453662
TI  - Thyroglobulin increases cell proliferation and suppresses Pax-8 in mesangial
      cells.
AB  - Thyroglobulin (Tg), has recently been identified as a transcriptional regulator
      of thyroid-restricted genes. The extrathyroidal expression of several of these
      genes (including the transcription factor Pax-8) together with the occurrence of
      specific Tg binding sites suggests a secondary role for Tg as a circulating
      hormone. In this study, we demonstrate using Northern analysis that Pax-8 is
      expressed in the mouse mesangial cell, and that its transcript levels are
      suppressed by Tg. These cells also express an asialoglycoprotein receptor, a
      receptor involved in Tg endocytosis in the thyroid, and a Tg transcript smaller
      than the 8.3-kb thyroidal form. Reverse transcriptase PCR showed that suppression
      of Pax-8 by Tg is correlated with reduced expression of bcl-2 apoptosis
      suppressor. Tg, but not triiodothyronine (T(3)) significantly increased MC
      proliferation above control as determined by DNA content of MC cultures. The
      effect of Tg on proliferation was not duplicated by either bovine serum albumin,
      gamma-globulins, lactoferrin, or the ASGPR-specific ligand,orosomucoid. These
      results suggest a possible endocrine role for Tg in regulating both Pax-8 related
      gene transcription and cell division in the mesangial cell.

PMID- 11453663
TI  - The bacterial nucleoside N(6)-methyldeoxyadenosine induces the differentiation of
      mammalian tumor cells.
AB  - Contrary to bacterial DNA, mammalian DNA contains very little if any N(6)
      methyldeoxyadenosine (MDA). The possible biological effect of this nucleoside on
      eukaryotic cells has been studied on different tumor cell lines. Addition of MDA
      to C6.9 glioma cells triggers a differentiation process and the expression of the
      oligodendroglial marker 2',3'-cyclic nucleotide 3'phosphorylase (CNP). The
      biological effects of N(6)-methyldeoxyadenosine were not restricted to C6.9
      glioma cells since differentiation was also observed on pheochromocytoma and
      teratocarcinoma cell lines and on dysembryoplastic neuroepithelial tumor cells.
      The precise mechanism by which MDA induces cell differentiation remains unclear,
      but is related to cell cycle modifications. These data point out the potential
      interest of N(6)-methyldeoxyadenosine as a novel antitumoral and differentiation
      agent. They also raise the intriguing question of the loss of adenine methylation
      in mammalian DNA. Furthermore, the finding that a methylated nucleoside found in
      bacterial DNA induces a biological process might have implications in gene
      therapy approaches when plasmid DNAs are injected into humans.

PMID- 11453664
TI  - Mechanical stress and nitric oxide influence leukotriene production in cartilage.
AB  - Nitric oxide (NO) and leukotrienes regulate a variety of processes in joint
      tissues and are frequently elevated in arthritis. Mechanical stress can induce
      biochemical and functional changes in cartilage that may influence mediator
      production. To investigate the relationship between mechanical stress and the
      production of leukotriene B(4) (LTB(4)) and NO, explants of porcine articular
      cartilage were subjected to mechanical compression for 1 h followed by 23 h
      recovery in the presence or absence of the NOS2 inhibitor 1400W. Dynamic
      compression significantly increased LTB(4) and LOX protein production in the
      presence of 1400W. The induced LTB(4) was functional as evidenced by its ability
      to promote chemotaxis of RBL-2H3 cells expressing the LTB(4) receptor. Increased
      LOX protein but not LTB(4) occurred in response to compression alone. These
      findings provide a direct link between mechanical stress and inflammation in
      cartilage and may have implications in the pathogenesis and treatment of
      arthritis.

PMID- 11453665
TI  - C/EBPbeta interacts with the P-enolpyruvate carboxykinase adipocyte-specific
      enhancer.
AB  - CCAAT/enhancer binding protein (C/EBP) family members are known to transactivate
      the gene encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC
      4.1.1.32) in hepatocytes via promoter proximal C/EBP response elements. PEPCK is
      also expressed in adipocytes; however, fibroblasts that are homozygous null for
      C/EBPbeta cannot express PEPCK when induced to differentiate into adipocytes
      (Tanaka et al., EMBO J. 16, 7432-7443, 1997). This along with our previous
      observation that an upstream adipocyte-specific enhancer contains multiple
      putative C/EBP binding elements suggested the possibility that C/EBPbeta
      transactivates the PEPCK gene in adipocytes via distal elements. We report here
      that C/EBPbeta transactivates a PEPCK-luciferase chimera in transient
      transfection assays. C/EBPbeta acted independently of peroxisome proliferator
      activated receptor gamma (PPARgamma) which is required for function of the
      enhancer. C/EBPbeta in nuclear extracts and recombinant C/EBPbeta bound three of
      the putative C/EBP-binding elements within the enhancer. C/EBPbeta binding to
      these three elements was strongly cooperative. However, mutation of all three
      elements did not affect reporter transactivation by C/EBPbeta suggesting that
      additional elements participate in PEPCK regulation or that the effects of
      C/EBPbeta are indirect.

PMID- 11453666
TI  - cAMP and DIF-1 repress the expression of the Dictyostelium MADS-box gene srfA at
      early stages of development.
AB  - The MADS-box-containing gene srfA from Dictyostelium discoideum codes for a
      putative transcription factor that plays multiple roles in the development of
      this social amoeba. We have investigated the regulation of srfA gene expression
      after disaggregation of the cells from developing structures. The steady-state
      level of srfA mRNA was strongly and transiently induced shortly after
      disaggregation. srfA is maximally expressed 20 min after cell disaggregation and
      decreases thereafter. Induction was not dependent on protein synthesis, PKA, the
      kinase SplA and SrfA itself. This phenomena does not occur when cells are
      disaggregated in a small volume of buffer, suggesting the presence of
      extracellular molecules that repress srfA gene expression. To test this
      hypothesis, several well-known extracellular signaling molecules were studied. We
      found that srfA mRNA induction can be efficiently repressed by addition of
      exogenous cAMP and DIF-1 to the buffer in which the cells were disaggregated.
      Addition of other extracellular compounds such as ammonia, adenosine, SDF-1, and
      SDF-2 had no effect. srfA promoter P2, specifically induced during slug
      migration, was responsible for this regulation by extracellular compounds.

PMID- 11453667
TI  - Implication of the small GTPase Rac1 in the apoptosis induced by UV in Rat-2
      fibroblasts.
AB  - Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response
      and also lead to apoptotic cell death. However, the role of Rac, a member of Rho
      family GTPases, in the UV-induced apoptosis has never been examined. In UV
      irradiated Rat-2 fibroblasts, nuclear fragmentation began to be observed within 2
      h and the total viability of Rat-2 cells were only about 15% at 6 h following by
      UV irradiation, whereas the total viability in Rat2-Rac(N17) cells stably
      expressing RacN17, a dominant negative Rac1 mutant, was almost close to 67%.
      Pretreatment with SB203580, a specific inhibitor of p38 kinase, likewise
      attenuated UV-induced cell death, but PD98059, a MEK inhibitor, did not. Thus,
      Rac1 and p38 kinase appear to be components in the apoptotic signaling pathway
      induced by UV irradiation in Rat-2 fibroblasts. In addition, our results show
      that p38 kinase stimulation by UV is dramatically inhibited by RacN17, suggesting
      that p38 kinase is situated downstream of Rac1 in the UV signaling to apoptosis.

PMID- 11453668
TI  - BXMAS1 identifies a cluster of homologous genes differentially expressed in B
      cells.
AB  - Characterization of genes activated by anti-IgM crosslinking of BL2 cells
      identified one gene, designated BXMAS1, that is predicted to be a novel cell
      surface receptor. The time course of activation indicates maximal transcriptional
      induction after 24 h. The predicted protein contains 977 aa residues, with a
      cytoplasmic domain containing 2 ITIM motifs. The ectodomain of the protein
      contains 6 repeats of characteristic 93 aa sequences which we have designated
      BXMAS1 domains. These domains correspond to 6 out of 8 Ig-like domains in BXMAS1.
      A search of the human genome revealed 5 additional closely linked homologous
      genes many of which contain BXMAS1 domains as well. Analysis of expression in
      cell lines and tissues suggests a general restriction of expression of these
      genes to B cells. These genes may be involved in B cell development and
      differentiation in peripheral lymphoid organs and may be useful markers of B cell
      stages.

PMID- 11453669
TI  - Role of the Sp family of transcription factors on glucagon receptor gene
      expression.
AB  - The glucagon receptor mediates the actions of glucagon on carbohydrate metabolism
      by the liver and on insulin release by the pancreatic beta-cell, which are key
      processes in the control of glucose homeostasis. The 5'-region of the mouse
      glucagon receptor gene has been recently cloned and two functional promoters were
      characterized. In the present study, we show that most of the glucagon receptor
      mRNA was transcribed from the distal promoter, in the mouse liver. In the distal
      promoter region, a GC-rich sequence with five putative binding sites for the Sp
      family of transcription factors was localized. To elucidate the role of these Sp1
      binding sites in the mouse MIN6 beta-cell line, the expression of reporter gene
      constructs containing deletion or point mutation of each site was carried out.
      Selective mutation of the second Sp1-binding site decreased the activity of the
      distal promoter. Electrophoretic mobility shift assay with a DNA fragment
      spanning the three first Sp1 sites confirmed that the second site bound
      specifically MIN6 nuclear proteins, and supershift using specific Sp antibodies
      demonstrated that it interacted with Sp3 but not Sp1 transcription factors. These
      data illustrate that the basal expression of the mouse glucagon receptor gene,
      driven by the distal promoter, requires an Sp1-binding site that binds Sp3
      proteins.

PMID- 11453670
TI  - Matrix vesicles and media vesicles as nonclassical pathways for the secretion of
      m-Calpain from MC3T3-E1 cells.
AB  - Calpain was generally believed to exist and function only in the cytoplasm.
      However, m-calpain has now been detected in the extracellular spaces of some
      kinds of tissue. In this study, we demonstrated the existence of m-calpain in the
      medium surrounding MC3T3-E1 cultures, and its activity by zymography. At the same
      time, the amount of lactate dehydrogenase in medium of MC3T3-E1 culture was
      extremely low compared with other cell cultures, suggesting that m-calpain found
      in the culture medium of MC3T3-E1 cells originated mainly from active secretion.
      Moreover, the secretion of m-calpain was not blocked by brefeldin A, implying
      that m-calpain may be secreted by a nonclassical pathway. Recently, MC3T3-E1 has
      been reported to produce matrix vesicles and media vesicles, and we demonstrated
      m-calpain in these vesicles produced by MC3T3-E1 cultures. We therefore concluded
      that these vesicles are partly responsible for the secretion of m-calpain into
      the culture medium of MC3T3-E1 cells.

PMID- 11453671
TI  - Mortality related to cold and air pollution in London after allowance for effects
      of associated weather patterns.
AB  - We looked for atypical weather patterns that could confound, and explain large
      inconsistencies in, conventional estimates of mortality due to SO(2), CO, and
      smoke. Using Greater London data for 1976-1995 in the linear
      temperature/mortality range 0-15 degrees C we determined weather patterns
      associated with pollutants (all deseasonalized) by single regressions of daily
      temperature, wind, rain, humidity, and sunshine at successive days advance and
      delay. Polluted days were colder (P<0.01 for SO(2), CO, and smoke) and less windy
      and rainy than usual, and this cold weather was more prolonged than usual with
      50% maximum temperature depression 5.9 days (95% interval 4.0-7.7) before high
      SO(2), compared to 2.0 (1.6-2.3) days before average cold days. We also used
      multiple regression of mortality at 50+ years of age on all these weather factors
      and pollutants at 0-, 1-, 2- to 4-, 5- to 13-, and 14- to 24-day delays to allow
      for the atypical weather patterns. This showed cold weather associated with 2.77
      excess deaths per million during 24 days following a 1 degrees C fall for 1 day,
      but no net excess deaths with SO(2) (mean 28.0 ppb) or CO (1.26 ppm). It
      suggested (P>0.05) some increase with smoke, perhaps acting as surrogate for
      PM(10), for which data were too scanty to analyze.

PMID- 11453672
TI  - Polychlorinated biphenyl congeners as markers of toxic equivalents of
      polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans in breast milk.
AB  - In breast milk, concentrations of polychlorinated biphenyls (PCBs) are higher
      than those of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans
      (PCDFs), making PCB analyses less time-consuming and expensive. We searched for
      PCB "markers" of PCDD/DF concentrations, by studying associations between
      concentrations of PCB and PCDD/DFs (expressed as toxic equivalents, TEQs) in
      breast milk from 27 women (primiparas, 22-35 years). These women donated breast
      milk in 1996-1999 together with 183 other primiparas from Uppsala County, Sweden.
      Regression analyses showed that both dioxin-like and non-dioxin-like penta- to
      hepta-chlorinated PCBs could be used as markers of TEQ concentrations in this
      group of women, in some cases after age adjustment of the regressions. The strong
      positive association between concentrations of dioxin-like PCB/DD/DFs and non
      dioxin-like PCBs will in future epidemiological studies make it difficult to
      separate Ah receptor-dependent effects from non-Ah receptor-dependent effects.
      With the use of regression equations and concentrations in breast milk samples
      collected in 1994, TEQ concentrations were estimated in the 1994 samples.
      Comparisons between estimated and measured concentrations indicated that
      associations between concentrations of marker substances and TEQs should be
      determined separately within each study population, in order to obtain reliable
      TEQ exposure assessments from PCB markers.

PMID- 11453673
TI  - Perinatal metabolism of dichlorodiphenyldichloroethylene in Nicaraguan mothers.
AB  - Umbilical cord and venous blood samples were collected at the time of delivery
      from 52 mothers living in urban and rural areas of the Atoya River basin,
      Nicaragua. In a subsample of 24 mothers that delivered by Cesarean section,
      abdominal adipose tissue samples were also collected, as was breast milk later in
      lactation. Cord and venous blood sera were analyzed for 13 organochlorine
      pesticides: 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (pp'-DDT); 1,1-dichloro
      2,2-bis(p-chlorophenyl)ethylene (pp'-DDE); pp'-dichlorophenyldichlorodiene (pp'
      DDD); alpha-hexachlorocyclohexane (alpha-HCH); beta-hexachlorocyclohexane (beta
      HCH); gamma-hexachlorocyclohexane (gamma-HCH); delta-hexachlorocyclohexane (delta
      HCH); toxaphene; dieldrin; endrin; aldrin; heptachlor; and heptachlor epoxide. In
      venous blood only pp'-DDE (100% of samples), pp'-DDT (1.92%), dieldrin (15.38%),
      heptachlor (15.38%), gamma-HCH (7.69%), beta-HCH (11.53%), and delta-HCH (1.92%)
      were found, whereas in cord blood only pp'-DDE (100%), pp'-DDT (3.84%), dieldrin
      (19.23%), and heptachlor (9.16%), were found. The persistent DDT metabolite pp'
      DDE, present in all samples of blood serum, adipose tissue, and breast milk, was
      studied in relation to maternal characteristics such as body mass index (BMI),
      age, lactation experience, and fetal pesticide acquisition. Mean venous (7.12
      microg/g) and cord (6.39 microg/g) pp'-DDE concentrations were not significantly
      different but were significantly correlated. pp'-DDE in maternal adipose tissue
      was positively correlated with pp'-DDE in cord blood (P=0.0001) and breast milk
      (P<0.0001) and marginally correlated with changes in BMI (r=-0.03088; P=0.06).
      There was a higher proportion of samples (58%) with a greater concentration of
      DDE in venous than in cord blood. Although DDE accumulation may be less during
      fetal development than during breast feeding, exposure during embryogenesis may
      be more important than during the postnatal period.

PMID- 11453674
TI  - Perlite exposure and 4-year change in lung function.
AB  - Perlite is a volcanic glass or amorphous aluminium silicate composed of 71-75%
      SiO(2). When heated to 800-1100 degrees C, it expands to form processed perlite,
      which has a low density, high surface area, and a low thermal conductivity. The
      objective was to determine the effect of perlite exposure on pulmonary function
      tests. Pulmonary function tests in conjunction with chest radiogram were carried
      out in 36 perlite-exposed workers and 22 unexposed office workers in 1992 and
      1996. Respirable dust level exceeded permissible dust levels in work places in
      the 4 years under study. Transfer coefficient (K(CO)) decline was significant in
      nonsmoker perlite-exposed workers (n=9), and found to be 5.28+/-0.71 (predicted
      4.32+/-0.11) and 3.84+/-0.96 (predicted 4.18+/-0.18) 1/min/mmHg, in 1992 and
      1996, respectively (P<0.001). Both smoker perlite workers and office workers
      showed significant obstruction to airflow in small airways with respect to
      predicted values and 4-year change in transfer factor (T(L), CO) was significant.
      Although predicted, 12-year perlite exposure did not lead to a decrease in mean
      pulmonary function test parameters, there was a tendency to a decline in T(L), CO
      in the 4-year study period, which may be due to high perlite dust levels. As
      early effects of perlite dust exposure may not be detected by spirometric
      measurements alone, the transfer coefficient should be added to spirometry.

PMID- 11453675
TI  - Human alveolar macrophage phagocytic function is impaired by aggregates of
      ultrafine carbon particles.
AB  - Alveolar macrophages (AM) were collected by bronchoalveolar lavage from healthy
      volunteers. The AM were loaded with small masses (0.03-3 microg/10(6) AM) of
      ultrafine carbon particle aggregates. The phagocytic activity of the cells was
      studied 20 h after the loading. Fluorescein-labeled silica particles (3 microm)
      were used as test particles and the attachment and ingestion processes were
      studied separately. In some experiments, AM were incubated with interferon-gamma
      (IFN-gamma) for 20 h before and during the test of phagocytic activity and during
      measurement of oxidative metabolism. The ingested carbon particles induced a dose
      related impairment of both the attachment and the ingestion processes with a
      marked impairment down to a carbon particle dose around 0.2 microg/10(6) AM. Such
      levels should reasonably occur after inhalation of existing concentrations of
      urban air particles, which to a considerable extent consist of aggregates of
      ultrafine particles with a carbon skeleton. Incubation with IFN-gamma (12.5 U/ml)
      also induced significant impairments in both the attachment and the ingestion
      processes. Loading with carbon further aggravated the effect of IFN-gamma. In
      contrast to earlier studies in rat AM, IFN-gamma did not impair the oxidative
      metabolism at rest in these human AM; instead the oxidative metabolism was
      increased. This difference was due to a difference between rat and human AM and
      not between rat and human IFN-gamma. Our results suggest that ingested
      environmental particles in AM, e.g., after an episode of high particle
      concentration, may impair phagocytic capacity of the cells, especially after
      infections that induce an increased production of IFN-gamma. Consequently, there
      might be a risk for additional infections. Moreover, inhaled particles not
      phagocytized by AM might damage the lung tissue.

PMID- 11453676
TI  - The two PM(2.5) (fine) and PM(2.5-10) (coarse) fractions: evidence of different
      biological activity.
AB  - Recent studies have shown that an increased concentration of environmental
      particulate matter (PM(10)) is related to many respiratory diseases. One major
      issue is whether the toxicity of the particles resides in some particular
      fraction as defined by chemical composition and size. The overall purpose of this
      study was to compare the in vitro toxicity of coarse (PM(2.5-10)) and fine
      (PM(2.5)) particulate matter, collected in an urban area of Rome, in relation to
      their physicochemical composition as assessed by analytic electron microscopy and
      atomic absorption spectroscopy. In particular, our aim was to evaluate the
      importance of particle physicochemical components in the induced toxicity. The in
      vitro toxicity assays used included human red blood cell hemolysis, cell
      viability, and nitric oxide (NO) release in the RAW 264.7 macrophage cell line.
      The hemolytic potential has been widely used as an in vitro toxicity screen and
      as a useful indicator of oxidative damage to biomembranes. We found that human
      erythrocytes underwent dose-dependent hemolysis when they were incubated with
      varying concentrations of fine and coarse particles. The hemolytic potential was
      greater for the fine particles than for the coarse particles in equal mass
      concentration. However, when data were expressed in terms of PM surface per
      volume unit of suspension, the two fractions did not show any significant
      hemolytic differences. This result suggested that the oxidative stress induced by
      PM on the cell membranes could be due mainly to the interaction between the
      particle surfaces and the cell membranes. RAW 264.7 macrophage cells challenged
      with particles showed decreased viability and an increased release of NO, a key
      inflammatory mediator, and both effects were not dose dependent in the tested
      concentration range. The fine particles were the most effective and the
      differences between the two size fractions in inducing these biological effects
      remained unchanged when the basis of comparison was changed from weight to
      surface measures. It seemed therefore that these differences relied on the
      different physicochemical nature of the particles. The main chemical difference
      between the two fractions resided in a greater abundance of C-rich particles with
      S traces in the fine fraction. Therefore, we cautiously suggest a role for these
      particles in the induction of toxicity.

PMID- 11453677
TI  - The lead content of blood serum.
AB  - Serum lead concentrations measured by stable isotope dilution with a thermal
      ionization mass spectrometer and blood lead concentrations measured by graphite
      furnace atomic absorption spectrophotometry are reported for 73 women of child
      bearing age resident in Los Angeles, California. The two quantities are related
      by the line y=0.00030+0.00241x (r=0.83), where y is serum lead concentration and
      x is blood lead concentration, both being expressed in units of microg/L. The
      linearity of the relationship appears to hold to a blood lead concentration of at
      least 60 microg Pb/L. The slope of the line indicates that lead in serum is 0.24%
      of that in whole blood in contrast to recent reports of between 0.32 and 0.35%
      determined by inductively coupled plasma (ICP) mass spectrometry with bismuth
      used as an internal standard. The discrepancy stems from the ICP mass
      spectrometer-generated curves not passing through the origin.

PMID- 11453678
TI  - Effects of ozone on evaporative water loss and thermoregulatory behavior of
      marine toads (Bufo marinus).
AB  - Ozone (O(3)) is a strong pulmonary irritant and causes a suite of respiratory
      tract inflammatory responses in humans and other mammals. In addition to lung
      injury, rodents exposed to O(3) exhibit a pronounced decrease in core body
      temperature at rest, which may offer a protective effect against O(3) damage. The
      effects of O(3) on other vertebrates have not been studied. Compared to
      individuals exposed to air (N=34), Bufo marinus toads exposed to O(3) (N=32) for
      4 h lost 3.78 g body mass (adjusted mean from analysis of covariance, body mass
      mean+/-SD, 90.1+/-21.90 g). We tested the thermoregulatory responses of 22 toads
      in a thermal gradient 1, 24, and 48 h after 4-h exposure to air (N=11) or 0.8 ppm
      O(3) (N=11). Individual toad thermal preferences were also significantly
      repeatable across all trials (intraclass correlation=0.66, P <0.001). We did not
      observe a direct effect of O(3) exposure on the preferred body temperatures (PBT)
      of toads. However, O(3) exposure did have an indirect effect on selected
      temperatures. Ozone-exposed toads with higher evaporative water loss rates, in
      turn, also selected lower PBT, voluntary minimum, and voluntary maximum
      temperatures 24 h post-exposure. Ozone exposure may thus alter both water balance
      and thermal preferences in anuran amphibians.

PMID- 11453680
TI  - Crystal structure of a T cell receptor Valpha11 (AV11S5) domain: new canonical
      forms for the first and second complementarity determining regions.
AB  - We describe the X-ray crystallographic structure of a murine T cell receptor
      (TCR) Valpha domain ("Valpha85.33"; AV11S5-AJ17) to 1.85 A resolution. The
      Valpha85.33 domain is derived from a TCR that recognizes a type II collagen
      peptide associated with the murine major histocompatibility complex (MHC) class
      II molecule, I-A(q). Valpha85.33 packs as a Valpha-Valpha homodimer with a highly
      symmetric monomer-monomer interface. The first and second complementarity
      determining regions (CDR1 and CDR2) of this Valpha are shorter than the CDRs
      corresponding to the majority of other Valpha gene families, and three
      dimensional structures of CDRs of these lengths have not been described
      previously. The CDR1 and CDR2 therefore represent new canonical forms that could
      serve as templates for AV11 family members. CDR3 of the Valpha85.33 domain is
      highly flexible and this is consistent with plasticity of this region of the TCR.
      The fourth hypervariable loop (HV4alpha) of AV11 and AV10 family members is one
      residue longer than that of other HV4alpha regions and shows a high degree of
      flexibility. The increase in length results in a distinct disposition of the
      conserved residue Lys68, which has been shown in other studies to play a role in
      antigen recognition. The X-ray structure of Valpha85.33 extends the database of
      canonical forms for CDR1 and CDR2, and has implications for antigen recognition
      by TCRs that contain related Valpha domains.

PMID- 11453681
TI  - Interplay between termination and translation machinery in eukaryotic
      selenoprotein synthesis.
AB  - Termination of translation in eukaryotes is catalyzed by eRF1, the stop codon
      recognition factor, and eRF3, an eRF1 and ribosome-dependent GTPase. In
      selenoprotein mRNAs, UGA codons, which typically specify termination, serve an
      alternate function as sense codons. Selenocysteine incorporation involves a
      unique tRNA with an anticodon complementary to UGA, a unique elongation factor
      specific for this tRNA, and cis-acting secondary structures in selenoprotein
      mRNAs, termed SECIS elements. To gain insight into the interplay between the
      selenocysteine insertion and termination machinery, we investigated the effects
      of overexpressing eRF1 and eRF3, and of altering UGA codon context, on the
      efficiency of selenoprotein synthesis in a transient transfection system.
      Overexpression of eRF1 does not increase termination at naturally occurring
      selenocysteine codons. Surprisingly, selenocysteine incorporation is enhanced.
      Overexpression of eRF3 did not affect incorporation efficiency. Coexpression of
      both factors reproduced the effects with eRF1 alone. Finally, we show that the
      nucleotide context immediately upstream and downstream of the UGA codon
      significantly affects termination to incorporation ratios and the response to eRF
      overexpression. Implications for the mechanisms of selenocysteine incorporation
      and termination are discussed.

PMID- 11453682
TI  - The relationship between translational control and mRNA degradation for the
      Escherichia coli threonyl-tRNA synthetase gene.
AB  - Expression of thrS, the gene encoding Escherichia coli threonyl-tRNA synthetase,
      is negatively autoregulated at the translational level. Regulation is due to the
      binding of threonyl-tRNA synthetase to its own mRNA at a site called the
      operator, located immediately upstream of the initiation codon. The present work
      investigates the relationship between regulation and mRNA degradation. We show
      that two regulatory mutations, which increase thrS expression, cause an increase
      in the steady-state mRNA concentration. Unexpectedly, however, the half-life of
      thrS mRNA in the derepressed mutants is equal to that of the wild-type,
      indicating that mRNA stability is independent of the repression level. All our
      results can be explained if one assumes that thrS mRNA is either fully translated
      or immediately degraded. The immediately degraded RNAs are never detected due to
      their extremely short half-lives, while the fully translated messengers share the
      same half-lives, irrespective of the mutations. The increase in the steady-state
      level of thrS mRNA in the derepressed mutants is simply explained by an increase
      in the population of translated molecules, i.e. those never bound by the
      repressor, ThrRS. Despite this peculiarity, thrS mRNA degradation seems to follow
      the classical degradation pathway. Its stability is increased in a strain
      defective for RNase E, indicating that an endonucleolytic cleavage by this enzyme
      is the rate-limiting process in degradation. We also observe an accumulation of
      small fragments corresponding to the 5' end of the message in a strain defective
      for polynucleotide phosphorylase, indicating that, following the endonucleolytic
      cleavages, fragments are normally degraded by 3' to 5' exonucleolytic trimming.
      Although mRNA degradation was suspected to increase the efficiency of
      translational control based on several considerations, our results indicate that
      inhibition of mRNA degradation has no effect on the level of repression by ThrRS.

PMID- 11453683
TI  - A novel mode of regulation of an RNA-cleaving DNAzyme by effectors that bind to
      both enzyme and substrate.
AB  - We describe a novel and general strategy for controlling the activity of RNA
      cleaving nucleic acid enzymes (ribozymes and DNAzymes) via the use of RNA and DNA
      effectors. Whereas in conventional heteroallosteric enzymes (including ribozymes)
      control of catalysis is achieved by the binding of effector molecules to the
      enzyme, in our strategy DNA and RNA regulators bind to both the enzyme and the
      substrate. The design of this system permits the control of catalysis even in the
      absence of a detailed knowledge of the secondary and tertiary structure of the
      relevant ribozyme or DNAzyme. Here, we utilize the ability of RNA and DNA to form
      branched three-way junctions to regulate the RNA-cleaving activity of the in
      vitro selected "10-23" DNAzyme by three orders of magnitude. Control is exercised
      by the ability of a DNA or RNA "regulator" to induce formation of stable and
      catalytically competent "three-way" enzyme-substrate-regulator complexes,
      relative to otherwise unstable and catalytically poor enzyme-substrate complexes.
      Such expansively regulated "three-way" ribozyme/DNAzyme systems might find
      utility in vivo to bring about the catalyzed destruction of one RNA transcript
      contingent on the presence in its immediate environment of another gene
      transcript.

PMID- 11453684
TI  - AA.AG@helix.ends: A:A and A:G base-pairs at the ends of 16 S and 23 S rRNA
      helices.
AB  - This study reveals that AA and AG oppositions occur frequently at the ends of
      helices in RNA crystal and NMR structures in the PDB database and in the 16 S and
      23 S rRNA comparative structure models, with the G usually 3' to the helix for
      the AG oppositions. In addition, these oppositions are frequently base-paired and
      usually in the sheared conformation, although other conformations are present in
      NMR and crystal structures. These A:A and A:G base-pairs are present in a variety
      of structural environments, including GNRA tetraloops, E and E-like loops,
      interfaced between two helices that are coaxially stacked, tandem G:A base-pairs,
      U-turns, and adenosine platforms. Finally, given structural studies that reveal
      conformational rearrangements occurring in regions of the RNA with AA and AG
      oppositions at the ends of helices, we suggest that these conformationally unique
      helix extensions might be associated with functionally important structural
      rearrangements.

PMID- 11453685
TI  - Flexibility and extensibility in the titin molecule: analysis of electron
      microscope data.
AB  - Muscle elasticity derives directly from titin extensibility, which stems from
      three distinct types of spring-like behaviour of the I-band portion of the
      molecule. With progressively greater forces and sarcomere lengths, the molecule
      straightens and then unfolds, first in the PEVK-region and then in individual
      immunoglobulin domains. Here, we report quantitative analysis of flexibility and
      extensibility in isolated titin molecules visualized by electron microscopy.
      Conformations displayed by molecules dried on a substrate vary from a random coil
      to rod-like, demonstrating highly flexible and easily deformable tertiary
      structure. The particular conformation observed depends on the "wettability" of
      the substrate during specimen preparation: higher wettability favours coiled
      conformations, whereas lower wettability results in more extended molecules.
      Extension is shown to occur during liquid dewetting. Statistical methods of
      conformational analysis applied to a population of coiled molecules gave an
      average persistence length 13.5(+/-4.5) nm. The close correspondence of this
      value to an earlier one from light-scattering studies confirms that conformations
      observed by microscopy closely reflected the equilibrium conformation in
      solution. Analysis of hydrodynamic forces exerted during dewetting also indicates
      that the force causing straightening of the molecules and extension of the PEVK
      region is in the picoNewton range, whereas unfolding of the immunoglobulin and
      fibronectin domains may require forces about tenfold higher. The microscope data
      directly illustrate the relationship between titin conformation and the magnitude
      of applied force. They also suggest the presence of torsional stiffness in the
      molecule, which may affect considerations of elasticity.

PMID- 11453686
TI  - Direct observation of different surface structures on high-resolution images of
      native halorhodopsin.
AB  - Halorhodopsin (HR) was investigated with atomic force microscopic techniques
      (AFM) in aqueous solution. Two-dimensional (2D) crystals of HR were obtained by
      purifying an HR membrane fraction with the same buoyant density as the purple
      membrane (HR-PM) from the overexpressing strain Halobacterium salinarum D2. The
      membrane patches of HR were immobilized on mica. Images with a resolution up to
      14 A were recorded. Crystals showed an orthogonal structure and the orientation
      of the molecules showed p42(1)2 symmetry; thus, alternate tetramers are inverted
      in the membrane. The crystal surface was found to display different structures
      depending on the imaging force used, indicating that some parts of the HR
      molecule are more rigid but others more compressible. From samples with single
      tetramers missing in the crystalline patches dimensions of the unit cell could be
      determined. Helix-connecting loops in single molecules of halorhodopsin were
      assigned. The images indicate that the large extracellular BC loop covers the
      whole molecule and is very flexible.

PMID- 11453687
TI  - Molecular organization of bovine rod cGMP-phosphodiesterase 6.
AB  - Phosphodiesterase 6 (PDE6), a multisubunit (alphabetagamma(2)delta) enzyme, plays
      a major role in visual function by hydrolysing cGMP in response to a light
      stimulus. Solubilized bovine rod PDE6 molecules depleted of their gamma subunits
      were purified to homogeneity from bovine retinal rods and their molecular
      organization was investigated by electron microscopy. Image analysis of single
      particles revealed the three-dimensional dimeric arrangement of the purified
      alphabetadelta complex, and the internal organization of each catalytic subunit
      into three distinct domains at a resolution of 2.8 nm. The relative volume of
      each domain is consistent with sequence analysis and functional data, which
      suggest that these domains correspond to the catalytic and two GAF domains. This
      hypothesis was confirmed by immunolabelling experiments, which located the N
      terminal part of the catalytic subunit where the major interaction between the
      two alphabeta subunits was found to occur. The 3D molecular organization of human
      platelet PDE5 appears highly homologous to that of bovine rod PDE6, as predicted
      by similarities in their primary sequences. These observations describe the
      quaternary organization of the catalytic PDE6 alphabeta complex, and place the
      catalytic and regulatory domains on a structural model.

PMID- 11453688
TI  - Covariance analysis of RNA recognition motifs identifies functionally linked
      amino acids.
AB  - The RNA recognition motif (RRM) is one of the most common eukaryotic protein
      motifs. RRM sequences form a conserved globular structure known as the RNA
      binding domain (RBD) or the ribonucleoprotein domain. Many proteins that contain
      RRM sequences bind RNA in a sequence-specific manner. To investigate the basis
      for the RNA-binding specificity of RRMs, we subjected 330 aligned RRM sequences
      to covariance analysis. The analysis revealed a single network of covariant amino
      acid pairs comprising the buried core of the RBD and a surface patch. Structural
      studies have implicated a subset of these residues in RNA binding. The covariance
      linkages identify a larger set of amino acid residues, including some not
      directly in contact with bound RNA, that may influence RNA-binding specificity.

PMID- 11453689
TI  - Linkage of EcoRI dissociation from its specific DNA recognition site to water
      activity, salt concentration, and pH: separating their roles in specific and non
      specific binding.
AB  - We have measured the dependencies of both the dissociation rate of specifically
      bound EcoRI endonuclease and the ratio of non-specific and specific association
      constants on water activity, salt concentration, and pH in order to distinguish
      the contributions of these solution components to specific and non-specific
      binding. For proteins such as EcoRI that locate their specific recognition site
      efficiently by diffusing along non-specific DNA, the specific site dissociation
      rate can be separated into two steps: an equilibrium between non-specific and
      specific binding of the enzyme to DNA, and the dissociation of non-specifically
      bound protein. We demonstrated previously that the osmotic dependence of the
      dissociation rate is dominated by the equilibrium between specific and non
      specific binding that is independent of the osmolyte nature. The remaining
      osmotic sensitivity linked to the dissociation of non-specifically bound protein
      depends significantly on the particular osmolyte used, indicating a change in
      solute-accessible surface area. In contrast, the dissociation of non-specifically
      bound enzyme accounts for almost all the pH and salt-dependencies. We observed
      virtually no pH-dependence of the equilibrium between specific and non-specific
      binding measured by the competition assay. The observed weak salt-sensitivity of
      the ratio of specific and non-specific association constants is consistent with
      an osmotic, rather than electrostatic, action. The seeming lack of a dependence
      on viscosity suggests the rate-limiting step in dissociation of non-specifically
      bound protein is a discrete conformational change rather than a general diffusion
      of the protein away from the DNA.

PMID- 11453690
TI  - X-ray structure of Escherichia coli pyridoxine 5'-phosphate oxidase complexed
      with pyridoxal 5'-phosphate at 2.0 A resolution.
AB  - Escherichia coli pyridoxine 5'-phosphate oxidase catalyzes the terminal step in
      the biosynthesis of pyridoxal 5'-phosphate by the FMN oxidation of pyridoxine 5'
      phosphate forming FMNH(2) and H(2)O(2). Recent studies have shown that in
      addition to the active site, pyridoxine 5'-phosphate oxidase contains a non
      catalytic site that binds pyridoxal 5'-phosphate tightly. The crystal structure
      of pyridoxine 5'-phosphate oxidase from E. coli with one or two molecules of
      pyridoxal 5'-phosphate bound to each monomer has been determined to 2.0 A
      resolution. One of the pyridoxal 5'-phosphate molecules is clearly bound at the
      active site with the aldehyde at C4' of pyridoxal 5'-phosphate near N5 of the
      bound FMN. A protein conformational change has occurred that partially closes the
      active site. The orientation of the bound pyridoxal 5'-phosphate suggests that
      the enzyme catalyzes a hydride ion transfer between C4' of pyridoxal 5'-phosphate
      and N5 of FMN. When the crystals are soaked with excess pyridoxal 5'-phosphate an
      additional molecule of this cofactor is also bound about 11 A from the active
      site. A possible tunnel exists between the two sites so that pyridoxal 5'
      phosphate formed at the active site may transfer to the non-catalytic site
      without passing though the solvent.

PMID- 11453691
TI  - Crystal structure of the 30 S ribosomal subunit from Thermus thermophilus:
      purification, crystallization and structure determination.
AB  - We describe the crystallization and structure determination of the 30 S ribosomal
      subunit from Thermus thermophilus. Previous reports of crystals that diffracted
      to 10 A resolution were used as a starting point to improve the quality of the
      diffraction. Eventually, ideas such as the addition of substrates or factors to
      eliminate conformational heterogeneity proved less important than attention to
      detail in yielding crystals that diffracted beyond 3 A resolution. Despite
      improvements in technology and methodology in the last decade, the structure
      determination of the 30 S subunit presented some very challenging technical
      problems because of the size of the asymmetric unit, crystal variability and
      sensitivity to radiation damage. Some steps that were useful for determination of
      the atomic structure were: the use of anomalous scattering from the LIII edges of
      osmium and lutetium to obtain the necessary phasing signal; the use of tunable,
      third-generation synchrotron sources to obtain data of reasonable quality at high
      resolution; collection of derivative data precisely about a mirror plane to
      preserve small anomalous differences between Bijvoet mates despite extensive
      radiation damage and multi-crystal scaling; the pre-screening of crystals to
      ensure quality, isomorphism and the efficient use of scarce third-generation
      synchrotron time; pre-incubation of crystals in cobalt hexaammine to ensure
      isomorphism with other derivatives; and finally, the placement of proteins whose
      structures had been previously solved in isolation, in conjunction with
      biochemical data on protein-RNA interactions, to map out the architecture of the
      30 S subunit prior to the construction of a detailed atomic-resolution model.

PMID- 11453692
TI  - The three-dimensional structure of alpha-actinin obtained by cryoelectron
      microscopy suggests a model for Ca(2+)-dependent actin binding.
AB  - The three-dimensional structure of alpha-actinin from rabbit skeletal muscle was
      determined by cryoelectron microscopy in combination with homology modeling of
      the separate domain structures based on results previously determined by X-ray
      crystallography and nuclear magnetic resonance spectroscopy. alpha-Actinin was
      induced to form two-dimensional arrays on a positively charged lipid monolayer
      and micrographs were collected from unstained, frozen hydrated specimens at tilt
      angles from 0 degrees to 60 degrees. Interpretation of the 15 A-resolution three
      dimensional structure was done by manually docking homologous models of the three
      key domains, actin-binding, three-helix motif and the C-terminal calmodulin-like
      domains. The initial model was refined quantitatively to improve its fit to the
      experimental reconstruction. The molecular model of alpha-actinin provides the
      first view of the overall structure of a complete actin cross-linking protein.
      The structure is characterized by close proximity of the C-terminal, calmodulin
      like domain to the linker between the two calponin-homology domains that comprise
      the actin-binding domain. This location suggests a hypothesis to explain the
      involvement of the C-terminal domain in Ca(2+)-dependent actin binding of non
      muscle isoforms.

PMID- 11453693
TI  - Crystal structures of the class D beta-lactamase OXA-13 in the native form and in
      complex with meropenem.
AB  - The therapeutic problems posed by class D beta-lactamases, a family of serine
      enzymes that hydrolyse beta-lactam antibiotics following an acylation-deacylation
      mechanism, are increased by the very low level of sensitivity of these enzymes to
      beta-lactamase inhibitors. To gain structural and mechanistic insights to aid the
      design of new inhibitors, we have determined the crystal structure of OXA-13 from
      Pseudomonas aeruginosa in the apo form and in complex with the carbapenem
      meropenem. The native form consisted of a dimer displaying an overall
      organisation similar to that found in the closely related enzyme OXA-10. In the
      acyl-enzyme complex, the positioning of the antibiotic appeared to be ensured
      mainly by (i) the covalent acyl bond and (ii) a strong salt-bridge involving the
      carboxylate moiety of the drug. Comparison of the structures of OXA-13 in the apo
      form and in complex with meropenem revealed an unsuspected flexibility in the
      region of the essential serine 115 residue, with possible consequences for the
      catalytic properties of the enzyme. In the apo form, the Ser115 side-chain is
      oriented outside the active site, whereas the general base Lys70 adopts a
      conformation that seems to be incompatible with the activation of the catalytic
      water molecule required for the deacylation step. In the OXA-13:meropenem
      complex, a 3.5 A movement of the backbone of the 114-116 loop towards the side
      chain of Lys70 was observed, which seems to be driven by a displacement of the
      neighbouring 91-104 loop and which results in the repositioning of the side-chain
      hydroxyl group of Ser115 toward the catalytic centre. Concomitantly, the side
      chain of Lys70 is forced to curve in the direction of the deacylating water
      molecule, which is then strongly bound and activated by this residue. However, a
      distance of ca 5 A separates the catalytic water molecule from the acyl carbonyl
      group of meropenem, a structural feature that accounts for the inhibition of OXA
      13 by this drug. Finally, the low level of penicillinase activity revealed by the
      kinetic analysis of OXA-13 could be related to the specific presence in position
      73 of a serine residue located close to the general base Lys70, which results in
      a decrease of the number of hydrogen-bonding interactions stabilising the
      catalytic water molecule.

PMID- 11453694
TI  - The 1.2 A resolution structure of the Con A-dimannose complex.
AB  - The complex between concanavalin A (Con A) and alpha1-2 mannobiose (mannose
      alpha1-2 mannose) has been refined to 1.2 A resolution. This is the highest
      resolution structure reported for any sugar-lectin complex. As the native
      structure of Con A to 0.94 A resolution is already in the database, this gives us
      a unique opportunity to examine sugar-protein binding at high resolution. These
      data have allowed us to model a number of hydrogen atoms involved in the binding
      of the sugar to Con A, using the difference density map to place the hydrogen
      atoms. This map reveals the presence of the protonated form of Asp208 involved in
      binding. Asp208 is not protonated in the 0.94 A native structure. Our results
      clearly show that this residue is protonated and hydrogen bonds to the sugar. The
      structure accounts for the higher affinity of the alpha1-2 linked sugar when
      compared to other disaccharides. This structure identifies different interactions
      to those predicted by previous modelling studies. We believe that the additional
      data presented here will enable significant improvements to be made to the sugar
      protein modelling algorithms.

PMID- 11453695
TI  - Crystal structure of native and Cd/Cd-substituted Dioclea guianensis seed lectin.
      A novel manganese-binding site and structural basis of dimer-tetramer
      association.
AB  - Diocleinae legume lectins are a group of oligomeric proteins whose subunits
      display a high degree of primary structure and tertiary fold conservation but
      exhibit considerable diversity in their oligomerisation modes. To elucidate the
      structural determinants underlaying Diocleinae lectin oligomerisation, we have
      determined the crystal structures of native and cadmium-substituted Dioclea
      guianensis (Dguia) seed lectin. These structures have been solved by molecular
      replacement using concanavalin (ConA) coordinates as the starting model, and
      refined against data to 2.0 A resolution. In the native (Mn/Ca-Dguia) crystal
      form (P4(3)2(1)2), the asymmetric unit contains two monomers arranged into a
      canonical legume lectin dimer, and the tetramer is formed with a symmetry-related
      dimer. In the Cd/Cd-substituted form (I4(1)22), the asymmetric unit is occupied
      by a monomer. In both crystal forms, the tetrameric association is achieved by
      the corresponding symmetry operators. Like other legume lectins, native D.
      guianensis lectin contains manganese and calcium ions bound in the vicinity of
      the saccharide-combining site. The architecture of these metal-binding sites (S1
      and S2) changed only slightly in the cadmium/cadmium-substituted form. A highly
      ordered calcium (native lectin) or cadmium (Cd/Cd-substituted lectin) ion is
      coordinated at the interface between dimers that are not tetrameric partners in a
      similar manner as the previously identified Cd(2+) in site S3 of a Cd/Ca-ConA. An
      additional Mn(2+) coordination site (called S5), whose presence has not been
      reported in crystal structures of any other homologous lectin, is present in
      both, the Mn/Ca and the Cd/Cd-substituted D. guianensis lectin forms. On the
      other hand, comparison of the primary and quaternary crystal structures of seed
      lectins from D. guianensis and Dioclea grandiflora (1DGL) indicates that the loop
      comprising residues 117-123 is ordered to make interdimer contacts in the D.
      grandiflora lectin structure, while this loop is disordered in the D. guianensis
      lectin structure. A single amino acid difference at position 131 (histidine in D.
      grandiflora and asparagine in D. guianensis) drastically reduces interdimer
      contacts, accounting for the disordered loop. Further, this amino acid change
      yields a conformation that may explain why a pH-dependent dimer-tetramer
      equilibrium exists for the D. guianensis lectin but not for the D. grandiflora
      lectin.

PMID- 11453696
TI  - Solution structure of the tumor necrosis factor receptor-1 death domain.
AB  - Tumor necrosis factor receptor-1 death domain (TNFR-1 DD) is the intracellular
      functional domain responsible for the receptor signaling activities. The solution
      structure of the R347K mutant of TNFR-1 DD was solved by NMR spectroscopy. A
      total of 20 structures were calculated by means of hybrid distance geometry
      simulated annealing using a total of 1167 distance constraints and 117 torsion
      angle constraints. The atomic rms distribution about the mean coordinate
      positions for the 20 structures for residues composing the secondary structure
      region is 0.40 A for the backbone atoms and 1.09 A for all atoms. The structure
      consists of six antiparallel alpha-helices arranged in a similar fashion to the
      other members of the death domain superfamily. The secondary structure and three
      dimensional structure of R347K TNFR1-DD are very similar to the secondary
      structure and deduced topology of the R347A TNFR1-DD mutant. Mutagenesis studies
      identified critical residues located in alpha2 and part of alpha3 and alpha4 that
      are crucial for self-interaction and interaction with TRADD. Structural
      superposition with previously solved proteins in the death domain superfamily
      reveals that the major differences between the structures reside in alpha2,
      alpha3, and alpha4. Interestingly, these regions correspond to the binding sites
      of TNFR1-DD, providing a structural basis for the specificity of death domain
      interactions and its subsequent signaling event.

PMID- 11453697
TI  - Solution structure of Escherichia coli glutaredoxin-2 shows similarity to
      mammalian glutathione-S-transferases.
AB  - Glutaredoxin 2 (Grx2) from Escherichia coli is distinguished from other
      glutaredoxins by its larger size, low overall sequence identity and lack of
      electron donor activity with ribonucleotide reductase. However, catalysis of
      glutathione (GSH)-dependent general disulfide reduction by Grx2 is extremely
      efficient. The high-resolution solution structure of E. coli Grx2 shows a two
      domain protein, with residues 1 to 72 forming a classical "thioredoxin-fold"
      glutaredoxin domain, connected by an 11 residue linker to the highly helical C
      terminal domain, residues 84 to 215. The active site, Cys9-Pro10-Tyr11-Cys12, is
      buried in the interface between the two domains, but Cys9 is solvent-accessible,
      consistent with its role in catalysis. The structures reveal the hither to
      unknown fact that Grx2 is structurally similar to glutathione-S-transferases
      (GST), although there is no obvious sequence homology. The similarity of these
      structures gives important insights into the functional significance of a new
      class of mammalian GST-like proteins, the single-cysteine omega class, which have
      glutaredoxin oxidoreductase activity rather than GSH-S-transferase conjugating
      activity. E. coli Grx 2 is structurally and functionally a member of this new
      expanding family of large glutaredoxins. The primary function of Grx2 as a GST
      like glutaredoxin is to catalyze reversible glutathionylation of proteins with
      GSH in cellular redox regulation including stress responses.

PMID- 11453698
TI  - Origin of apparent fast and non-exponential kinetics of lysozyme folding measured
      in pulsed hydrogen exchange experiments.
AB  - Folding of lysozyme at pH 5.2 is a complex processes. After rapid collapse (<1
      ms) kinetic partitioning into a slow and fast folding pathway occurs. The fast
      pathway leads directly to the native structure (N), whereas the slow pathway goes
      through a partially folded intermediate (I(1)) with native-like secondary
      structure in the alpha-domain. This mechanism is in agreement with data from a
      large number of spectroscopic probes, from changes in the radius of gyration and
      from measurements on the time-course of the populations of the different species.
      Results from pulsed hydrogen exchange experiments, in contrast, revealed that the
      secondary structure of I(1) and of N is formed significantly faster than changes
      in spectroscopic properties occur and showed large variations in the protection
      kinetics of individual amide sites. We investigated the molecular origin of the
      rapid amide protection by quantitatively simulating all kinetic processes during
      the pulse-labeling experiments. Absorbance and fluorescence-detected folding
      kinetics showed that the early events in lysozyme folding are accelerated under
      exchange conditions (pH 9.2) and that a change in folding mechanism occurs due to
      the transient population of an additional intermediate (I(2)). This leads to
      kinetic competition between exchange and folding during the exchange pulse and to
      incomplete labeling of amide sites with slow intrinsic exchange rates. As a
      result, apparently faster and non-exponential kinetics of amide protection are
      measured in the labeling experiments. Our results further suggest that collapsed
      lysozyme (C) and I(1) have five and ten-times reduced free exchange rates,
      respectively, due to limited solvent accessibility.

PMID- 11453699
TI  - The palmitoyl groups of lung surfactant protein C reduce unfolding into a
      fibrillogenic intermediate.
AB  - Lung surfactant protein C (SP-C) is a lipophilic peptide that converts from a
      monomeric alpha-helical state into beta-sheet conformation and forms amyloid
      fibrils, a process which appears to be accelerated by removal of its two S
      palmitoyl groups, and elevated amounts of non-palmitoylated SP-C are found in
      pulmonary alveolar proteinosis. Here, we used mass spectrometry to study the
      first step in fibrillogenesis of di-, mono- and non-palmitoylated SP-C. First,
      the individual decreases in concentration of monomeric alpha-helical forms of the
      three peptides in an acidified aqueous organic solvent mixture were monitored by
      electrospray (ES) mass spectrometry. Dipalmitoylated SP-C disappeared with a
      first-order rate constant of 0.01 h(-1), corresponding to a t(1/2) of 70 hours,
      while SP-C missing one or two palmitoyl groups disappeared with a rate constant
      of 0.02 h(-1), t(1/2)=35 hours. This supports the suggestion that the acyl chains
      stabilise helical SP-C, and that small differences in helix stability can
      influence fibril formation. The rates of disappearance of the monomeric alpha
      helical peptides are much faster than the disappearance of total soluble SP-C
      (t(1/2)=15 days for SP-C forms soluble after centrifugation at 20,000 g), which
      suggests that fibril formation is preceded by formation of soluble aggregates.
      Next, we used matrix-assisted laser desorption/ionisation (MALDI) mass
      spectrometry to measure hydrogen-->deuterium (H/(2)H) exchange in di-, mono- and
      non-palmitoylated SP-C in acidified aqueous organic solvents. All three species
      contain a rigid alpha-helix in their monomeric forms and no difference in
      deuterium uptake between SP-C with and without palmitoyl groups could be
      detected. The decreased stability of mono- and non-palmitoylated SP-C observed by
      ES mass spectrometry is thus not associated with partial unwinding of the helix
      in solution. Finally, SP-C was shown to unfold during the ES process (where ions
      are transferred from the solution to the gas phase) and the unfolded forms of di
      , mono- and non-palmitoylated SP-C undergo H/(2)H exchange. This, together with
      the findings from MALDI H/(2)H experiments that the alpha-helix does not
      exchange, indicates that no partly helical intermediates exist and that the
      unfolding is highly cooperative.

PMID- 11453700
TI  - Susceptibility of mouse mammary glands to murine gammaherpesvirus 72 (MHV-72)
      infection: evidence of MHV-72 transmission via breast milk.
AB  - Murine gammaherpesvirus 72 (MHV-72) is a virus of wild rodents and serves as a
      convenient small animal model to understand the pathogenesis of Epstein-Barr
      virus (EBV) and human herpesvirus 8 (HHV8) infection. In laboratory mice MHV-72
      causes an acute infection of lung epithelial cells and establishes the latency in
      B lymphocytes. In this study, we investigated athymic nude and immunocompetent
      mice for distribution of virus in organs after infection with MHV-72. Ten days
      following subcutaneous dorsal injection of nude mice, virus replicated in lungs,
      lymphoid organs, salivary glands and also in mammary glands. The virus titre
      decreased by day 21 post-infection in former tissues, but increased in mammary
      glands. Presence of virus DNA sequences was detected in the lymphoid and non
      lymphoid tissues until the death of the animals (about 1 month post-infection).
      Infection of immunocompetent mice with MHV-72 induced replication of virus up to
      42 days post-infection in mammary glands reaching the highest level of infectious
      virus at day 8 post-infection. These data show that there is latent infection in
      mice never detected before. Moreover, virus DNA was detected using nested PCR (by
      amplification of a portion of gp150 gene sequence) in the mammary glands and the
      milk of mouse mothers infected with MHV-72 2 days before delivery. We
      demonstrated the presence of virus DNA also in the milk removed from the stomach
      of non-infected newborn mice, which were nourished by infected mothers (wet
      nurses) for 1 or 2 days. The failure to detect the virus DNA in newborn mice
      lungs confirmed that they did not become infected from wet-nurses by the
      intranasal route. This suggests that MHV may be naturally transmitted to newborn
      mice via breast milk.

PMID- 11453701
TI  - Localization of Shiga toxins of enterohaemorrhagic Escherichia coli in kidneys of
      paediatric and geriatric patients with fatal haemolytic uraemic syndrome.
AB  - Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia,
      thrombocytopenia and renal failure. Infection with enterohaemorrhagic Escherichia
      coli (EHEC), mainly O157:H7, has been strongly implicated as the major cause of
      HUS in children. The pathogenesis of HUS caused by the infection is not well
      understood and the defined sites of Stx in kidney of EHEC-infected humans has not
      been clearly demonstrated. The aim of this study was to investigate and compare
      the locations of Stx deposition in kidneys of paediatric and geriatric patients
      who died from enterohaemorrhagic E. coli O157 (EHEC) associated HUS, using an
      immunoperoxidase staining of the tissues. The study revealed that binding of Stx
      was relatively less and limited only to the renal tubules of an adult case (81
      years old), while more binding was found at both renal tubules and glomeruli of
      an infant case (21 months old). The Stx binding in the infant's glomeruli was at
      podocytes, mesangial and endothelial cells. It has been known that young children
      are more susceptible than adults to HUS. One possibility for this is that the
      more extensive binding of the Stx to the kidney tissue of the paediatric patient
      might be due to the higher synthesis and expression of Stx receptors, i.e. Gb(3),
      in infants and less so in the aged individuals. However, other alternatives are
      possible, for example, the difference in stage of HUS in individual patients.
      Thus it is too early to draw any conclusion on this enigma and further
      investigation is required.

PMID- 11453702
TI  - Escherichia coli K1 purA and sorC are preferentially expressed upon association
      with human brain microvascular endothelial cells.
AB  - In order to better understand the events that allow Escherichia coli K1 to cross
      the blood-brain barrier we used differential fluorescence induction to identify
      bacterial genes that are preferentially expressed when associated with human
      brain microvascular endothelial cells (HBMEC), which comprise the blood-brain
      barrier. Random gene fusions of E. coli K1 DNA were created in a promoterless gfp
      vector and gene fusion libraries were incubated with and without HBMEC. The cells
      were subjected to a series of fluorescence-activated cell sorting screens to
      identify promoter fusions which lead to fluorescence when bacteria were
      associated with HBMEC, yet not fluorescent when grown in media alone. Two genes
      were identified, purA (encodes adenylosuccinate synthetase) and a sorC homologue
      (encodes a member of the sorC family of transcriptional regulators), whose
      expression were preferentially induced when bacteria were associated with
      eukaryotic cells. Individual gene disruption mutants of E. coli K1 purA and sorC
      demonstrated significantly decreased HBMEC invasion phenotype in vitro, when
      compared to the wild-type strain, and could be complemented when the respective
      wild-type sequences were supplied in trans. The purA and sorC mutants were
      deficient in their ability to grow in defined minimal media, without adenine, and
      with sorbose as sole carbon source, respectively, yet capable of normal growth in
      complex media. We have identified novel phenotypes associated with E. coli K1
      purA and sorC, which provide evidence that these genes contribute to the invasion
      of HBMEC.

PMID- 11453703
TI  - Identification of a major, CsrRS-regulated secreted protein of Group A
      streptococcus.
AB  - CsrR/CsrS (CovR/CovS) is a two-component regulator of extracellular virulence
      factors in Group A streptococcus, but the full range of regulated exoproteins is
      unknown. Since CsrR represses expression of regulated factors, culture supernates
      of wild-type and CsrR(-)mutant strains were compared by two-dimensional gel
      electrophoresis (2DGE) to identify regulated exoproteins. Supernates of
      DeltacsrRS(-)mutant, but not wild-type, bacteria contained an abundant 23 kDa
      protein. The N-terminal sequence of this spot corresponded to a putative open
      reading frame (ORF) in the streptococcal genome. In a mobility shift assay,
      phosphorylated CsrR bound to a PCR amplicon that included sequences upstream of
      this ORF. By primer extension analysis, the ORF (designated mspA, for Mucoidy
      associated Secreted Protein) was expressed in mid- and late-exponential phase in
      a DeltacsrRS(-)mutant. The presence of an in-frame deletion in mspA did not
      affect colony appearance, mucoidy or in vitro growth, and there was no difference
      between DeltamspA and wild-type strains in a mouse model of skin infection. MspA
      is co-regulated with other factors required for dermonecrosis (e.g. capsule,
      streptolysin S and purogenic exotoxin B); however, deletion of this gene does not
      affect expression of hyaluronic acid capsule or severity of skin infection in
      mice.

PMID- 11453704
TI  - Salmonella typhimurium-induced cytokine production and surface molecule
      expression by murine macrophages.
AB  - The influence of Salmonella enterica serovar Typhimurium (S. typhimurium) on co
      stimulatory molecule expression, cytokine production and induction of nitric
      oxide synthase (iNOS) by murine macrophages (Mphi), as well as the influence of
      the phoP locus on these aspects of S. typhimurium-Mphi interaction, was
      characterized. Pulsing Mphi with S. typhimurium resulted in increased surface
      expression of MHC-I, MHC-II, CD86 and CD54. Furthermore, co-incubating S.
      typhimurium with Mphi resulted in interleukin (IL)-12p40, IL-6 and tumor necrosis
      factor-alpha production as well as iNOS induction while IL-12p70 was not
      detectable. Finally, although phoP did not influence the level of surface
      molecule expression or cytokine production by S. typhimurium-pulsed Mphi phoP did
      influence the level of iNOS induction. Together these data show that S.
      typhimurium interaction with Mphi activates these cells in ways that may enhance
      their ability to productively stimulate Salmonella-specific T cells following
      phagocytic processing and presentation of Salmonella antigens.

PMID- 11453705
TI  - Escherichia coli S fimbriae do not contribute to intestinal colonization or
      translocation in the gnotobiotic rat.
AB  - Escherichia coli S fimbriae, which bind to sialic acid residues, are a virulence
      factor for extraintestinal infection, but also promote binding to intestinal
      epithelial cells. In this study, we investigated whether S fimbriae would enhance
      intestinal colonization by E. coli or promote translocation to extraintestinal
      sites. A mixture of two E. coli isogenic strains both expressing type-1 fimbriae
      but differing in the carriage of S fimbriae (Sfim+ and Sfim-) were given
      perorally to germfree neonatal, infant or adult rats. The Sfim+ bound better to
      rat intestinal mucus and epithelial cells. However, both strains colonized
      equally well in both the small and large intestine and their rate of
      translocation to the mesenteric lymph nodes was similar. Infant rats had higher
      E. coli levels in the small intestine than adult rats, but their translocation
      rates were lower. This was at least partly due to their milk diet, since weaned
      infant rats had more translocating bacteria than infant rats that continued
      suckling their mother. The results suggest that S fimbriae, despite binding to
      intestinal epithelial cells and mucus, do not contribute to either colonization
      or translocation in the gnotobiotic rat.

PMID- 11453706
TI  - Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal
      disease. A meta-analysis of patient-level data.
AB  - PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic
      renal disease. DATA SOURCES: 11 randomized, controlled trials comparing the
      efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of
      regimens without ACE inhibitors in predominantly nondiabetic renal disease. STUDY
      SELECTION: Studies were identified by searching the MEDLINE database for English
      language studies evaluating the effects of ACE inhibitors on renal disease in
      humans between May 1977 (when ACE inhibitors were approved for trials in humans)
      and September 1997. DATA EXTRACTION: Data on 1860 nondiabetic patients were
      analyzed. DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Patients in
      the ACE inhibitor group had a greater mean decrease in systolic and diastolic
      blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to
      3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to
      0.59 g/d]). After adjustment for patient and study characteristics at baseline
      and changes in systolic blood pressure and urinary protein excretion during
      follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94)
      for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome
      of doubling of the baseline serum creatinine concentration or end-stage renal
      disease. Patients with greater urinary protein excretion at baseline benefited
      more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the
      data were inconclusive as to whether the benefit extended to patients with
      baseline urinary protein excretion less than 0.5 g/d. CONCLUSION:
      Antihypertensive regimens that include ACE inhibitors are more effective than
      regimens without ACE inhibitors in slowing the progression of nondiabetic renal
      disease. The beneficial effect of ACE inhibitors is mediated by factors in
      addition to decreasing blood pressure and urinary protein excretion and is
      greater in patients with proteinuria. Angiotensin-converting inhibitors are
      indicated for treatment of nondiabetic patients with chronic renal disease and
      proteinuria and, possibly, those without proteinuria.

PMID- 11453707
TI  - Performance of helical computed tomography in unselected outpatients with
      suspected pulmonary embolism.
AB  - BACKGROUND: Helical computed tomography (CT) is commonly used to diagnose
      pulmonary embolism, although its operating characteristics have been
      insufficiently evaluated. OBJECTIVE: To assess the sensitivity and specificity of
      helical CT in suspected pulmonary embolism. DESIGN: Observational study. SETTING:
      Emergency department of a teaching and community hospital. PATIENTS: 299 patients
      with clinically suspected pulmonary embolism and a plasma D -dimer level greater
      than 500 microgram/L. INTERVENTION: Pulmonary embolism was established by using a
      validated algorithm that included clinical assessment, lower-limb compression
      ultrasonography, lung scanning, and pulmonary angiography. MEASUREMENTS:
      Sensitivity, specificity, and likelihood ratios of helical CT and interobserver
      agreement. Helical CT scans were withheld from clinicians and were read 3 months
      after acquisition by radiologists blinded to all clinical data. RESULTS: 118
      patients (39%) had pulmonary embolism. In 12 patients (4%), 2 of whom had
      pulmonary embolism, results of helical CT were inconclusive. For patients with
      conclusive results, sensitivity of helical CT was 70% (95% CI, 62% to 78%) and
      specificity was 91% (CI, 86% to 95%). Interobserver agreement was high (kappa =
      0.823 to 0.902). The false-negative rate was lower for helical CT used after
      initial negative results on ultrasonography than for helical CT alone (21% vs.
      30%). Use of helical CT after normal results on initial ultrasonography and
      nondiagnostic results on lung scanning had a false-negative rate of only 5% and a
      false-positive rate of only 7%. CONCLUSION: Helical CT should not be used alone
      for suspected pulmonary embolism but could replace angiography in combined
      strategies that include ultrasonography and lung scanning.

PMID- 11453709
TI  - Excluding pulmonary embolism at the bedside without diagnostic imaging:
      management of patients with suspected pulmonary embolism presenting to the
      emergency department by using a simple clinical model and d-dimer.
AB  - BACKGROUND: The limitations of the current diagnostic standard, ventilation
      perfusion lung scanning, complicate the management of patients with suspected
      pulmonary embolism. We previously demonstrated that determining the pretest
      probability can assist with management and that the high negative predictive
      value of certain D -dimer assays may simplify the diagnostic process. OBJECTIVE:
      To determine the safety of using a simple clinical model combined with D -dimer
      assay to manage patients presenting to the emergency department with suspected
      pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Emergency
      departments at four tertiary care hospitals in Canada. PATIENTS: 930 consecutive
      patients with suspected pulmonary embolism. INTERVENTIONS: Physicians first used
      a clinical model to determine patients' pretest probability of pulmonary embolism
      and then performed a D -dimer test. Patients with low pretest probability and a
      negative D -dimer result had no further tests and were considered to have a
      diagnosis of pulmonary embolism excluded. All other patients underwent
      ventilation-perfusion lung scanning. If the scan was nondiagnostic, bilateral
      deep venous ultrasonography was done. Whether further testing (by serial
      ultrasonography or angiography) was done depended on the patients' pretest
      probability and the lung scanning results. MEASUREMENTS: Patients received a
      diagnosis of pulmonary embolism if they had a high-probability ventilation
      perfusion scan, an abnormal result on ultrasonography or pulmonary angiography,
      or a venous thromboembolic event during follow-up. Patients for whom the
      diagnosis was considered excluded were followed up for 3 months for the
      development of thromboembolic events. RESULTS: The pretest probability of
      pulmonary embolism was low, moderate, and high in 527, 339, and 64 patients
      (1.3%, 16.2%, and 37.5% had pulmonary embolism), respectively. Of 849 patients in
      whom a diagnosis of pulmonary-embolism had initially been excluded, 5 (0.6% [95%
      CI, 0.2% to 1.4%]) developed pulmonary embolism or deep venous thrombosis during
      follow-up. However, 4 of these patients had not undergone the proper diagnostic
      testing protocol. In 7 of the patients who received a diagnosis of pulmonary
      embolism, the physician had performed more diagnostic tests than were called for
      by the algorithm. In 759 of the 849 patients in whom pulmonary embolism was not
      found on initial evaluation, the diagnostic protocol was followed correctly. Only
      1 (0.1% [CI, 0.0% to 0.7%]) of these 759 patients developed thromboembolic events
      during follow-up. Of the 437 patients with a negative D -dimer result and low
      clinical probability, only 1 developed pulmonary embolism during follow-up; thus,
      the negative predictive value for the combined strategy of using the clinical
      model with D -dimer testing in these patients was 99.5% (CI, 99.1% to 100%).
      CONCLUSION: Managing patients for suspected pulmonary embolism on the basis of
      pretest probability and D -dimer result is safe and decreases the need for
      diagnostic imaging.

PMID- 11453710
TI  - Management of suspected deep venous thrombosis in outpatients by using clinical
      assessment and D-dimer testing.
AB  - BACKGROUND: When deep venous thrombosis is suspected, objective testing is
      required to confirm or refute the diagnosis. OBJECTIVE: To determine whether the
      combination of a low clinical suspicion and a normal D -dimer result rules out
      deep venous thrombosis. DESIGN: Prospective cohort study. SETTING: Three tertiary
      care hospitals in Canada. PATIENTS: 445 outpatients with a suspected first
      episode of deep venous thrombosis. INTERVENTIONS: Patients were categorized as
      having low, moderate, or high pretest probability of thrombosis and underwent
      whole-blood D -dimer testing. Patients with a low pretest probability and a
      negative result on the D -dimer test had no further diagnostic testing and
      received no anticoagulant therapy. Additional diagnostic testing was done in all
      other patients. MEASUREMENTS: Venous thromboembolic events during 3-month follow
      up. RESULTS: 177 (40%) patients had both a low pretest probability and a negative
      D -dimer result. One of these patients had deep venous thrombosis during follow
      up (negative predictive value, 99.4% [95% CI, 96.9% to 100%]). CONCLUSION: The
      combination of a low pretest probability of deep venous thrombosis and a negative
      result on a whole-blood D -dimer test rules out deep venous thrombosis in a large
      proportion of symptomatic outpatients.

PMID- 11453711
TI  - Adjustments for center in multicenter studies: an overview.
AB  - Increasingly, investigators rely on multicenter or multigroup studies to
      demonstrate effectiveness and generalizability. Authors too often overlook the
      analytic challenges in these study designs: the correlation of outcomes and
      exposures among patients within centers, confounding of associations by center,
      and effect modification of treatment or exposure across center. Correlation or
      clustering, resulting from the similarity of outcomes among patients within a
      center, requires an adjustment to confidence intervals and P values, especially
      in observational studies and in randomized multicenter studies in which treatment
      is allocated by center rather than by individual patient. Multicenter designs
      also warrant testing and adjustment for the potential bias of confounding by
      center, and for the presence of effect modification or interaction by center.
      This paper uses examples from the recent biomedical literature to highlight the
      issues and analytic options.

PMID- 11453712
TI  - Update in dermatology.

PMID- 11453713
TI  - Power Shortage: clinical trials testing the "homocysteine hypothesis" against a
      background of folic acid-fortified cereal grain flour.
AB  - Large randomized, controlled trials of total homocysteine-lowering therapy for
      the potential reduction of cardiovascular disease outcomes are ongoing in the
      United States and Canada. These trials are the Vitamin Intervention for Stroke
      Prevention (VISP) trial, the Women's Antioxidant Cardiovascular Disease Study
      (WACS), and the Heart Outcomes Prevention Evaluation (HOPE-2). However, the
      dramatic effect of policies mandating fortification of cereal grain flour
      products with folic acid may reduce the statistical power of these trials. All
      three trials assume that the active treatment groups will achieve the same mean
      effects of total homocysteine-lowering therapy as those reported in the absence
      of folic acid-fortified cereal grain flour. This paper examines this assumption
      using data from studies of total homocysteine-lowering therapy in U.S. and
      Canadian patients with cardiovascular disease who were exposed to products made
      with folic acid-fortified cereal grain flour. These data showed that the VISP
      trial, HOPE-2, and WACS will probably achieve only approximately 20% to 25% of
      the projected treatment effects of mean total homocysteine-lowering therapy (1.0
      to 1.5 micromol/L vs. 4.0 to 6.0 micromol/L). As a result, all three trials will
      be substantially underpowered to test the specific hypotheses of total
      homocysteine-lowering therapy identified a priori. In contrast, renal transplant
      recipients have a persistent excess prevalence of hyperhomocysteinemia in the era
      of fortification but remain very responsive to supraphysiologic doses of folic
      acid-based supplementation (mean reduction in total homocysteine level, 5.0 to
      6.0 micromol/L). Therefore, unlike other populations with normal renal function
      that are at high risk for cardiovascular disease but are profoundly affected by
      fortification efforts, renal transplant recipients continue to merit serious
      consideration for a controlled trial of the "homocysteine hypothesis."

PMID- 11453714
TI  - The effect of angiotensin-converting enzyme inhibitors on the progression of
      nondiabetic renal disease: a pooled analysis of individual-patient data from 11
      randomized, controlled trials.

PMID- 11453715
TI  - Association of hepatitis C and diabetes mellitus.

PMID- 11453716
TI  - Association of hepatitis C and diabetes mellitus.

PMID- 11453718
TI  - Cocaine-related vasculitis causing upper-limb peripheral vascular disease.

PMID- 11453719
TI  - Severe hepatitis in a patient taking cetirizine.

PMID- 11453722
TI  - Physician burnout.

PMID- 11453723
TI  - The less harmful cigarette: a controversial issue. a tribute to Ernst L. Wynder.
AB  - The dose-response relationship between number of cigarettes smoked and risk for
      lung cancer was established in 1950 by epidemiological studies. Laboratory assays
      with tobacco tar on mouse skin and smoke inhalation experiments with hamsters
      provided further evidence for this relationship. In cigarette smoke, among 4800
      identified compounds, 69 are carcinogens, and several are tumor promoters or
      cocarcinogens. The major toxic agents are nicotine, carbon monoxide, hydrogen
      cyanide, nitrogen oxides, some volatile aldehydes, some alkenes, and some
      aromatic hydrocarbons. Public health information and education have led to a
      reduction of cigarette smokers among U.S. adults from 40 to 25%. However, in high
      school students, smoking increased to 35% and in adults with less than a high
      school education it remains high at 33.3%. Intervention studies were augmented
      with attempts of risk reduction by changing the tobacco composition and makeup of
      cigarettes. This led to cigarettes that, according to the FTC, reduced the tar
      and nicotine yields from an average of 37 and 2.7 mg to 12 and 0.85 mg. The
      anticipated reduction of mortality rates from chronic diseases among cigarette
      smokers did not occur, primarily, because of a major adjustment in smoking
      intensity and depth of inhalation by the habitual smokers. It is, therefore,
      imperative that smoking control efforts are intensified and that, short of
      banning cigarette sales, cigarettes delivering smoke with the lowest potential
      for toxicity, addiction, and carcinogenicity are declared a matter of public
      health policy.

PMID- 11453724
TI  - Organotin-induced caspase activation and apoptosis in human peripheral blood
      lymphocytes.
AB  - In the present study, we show that the immunotoxicant, tributyltin (TBT), induces
      a dose-dependent activation of caspases followed by typical apoptotic morphology
      in resting human peripheral blood lymphocytes. TBT also caused an early loss of
      mitochondrial membrane potential (Delta(Psi)(m)) and release of cytochrome c,
      suggesting that apoptosis was triggered by the mitochondrial pathway. When CD4+ T
      cells were sorted from peripheral blood and exposed to TBT for 30 min, caspase
      activation and apoptosis were induced. Interestingly, in the sorted CD8+ T-cell
      population, caspase activation was not observed until 2 h of TBT exposure,
      suggesting that these cells were more resistant toward TBT. Moreover, a time
      dependent induction of caspase activity was also detected in CD3-stimulated
      peripheral blood lymphocytes. This caspase activation was not associated with
      cytochrome c release or loss of mitochondrial Delta(Psi) and did not lead to
      apoptotic morphology, although it did lead to both PARP and DFF cleavage. We also
      noticed a concomitant induction of Hsp27, and it awaits to be seen if this
      chaperone may interfere with the processing of nuclear protein substrates
      downstream from these primary caspase-3 substrates. Moreover, no increase in
      caspase activation or induction of apoptosis was observed after TBT treatment in
      these cells. Instead, the cells were directed toward necrotic deletion. Taken
      together, these data suggest that TBT-induced deletion of peripheral lymphocytes
      is likely to be a component in the overall risk for immunotoxic responses in
      exposed humans.

PMID- 11453725
TI  - Covalent binding of acrylonitrile to specific rat liver glutathione S
      transferases in vivo.
AB  - Acrylonitrile (AN) is an industrial vinyl monomer that is acutely toxic. When
      administered to rats, AN covalently binds to tissue proteins in a dose-dependent
      but nonlinear manner [Benz, F. W., Nerland, D. E., Li, J., and Corbett, D. (1997)
      Fundam. Appl. Toxicol. 36, 149-156]. The nonlinearity in covalent binding stems
      from the fact that AN rapidly depletes liver glutathione after which the covalent
      binding to tissue proteins increases disproportionately. The identity of the
      tissue proteins to which AN covalently binds is unknown. The experiments
      described here were conducted to begin to answer this question. Male Sprague
      Dawley rats were injected subcutaneously with 115 mg/kg (2.2 mmol/kg) [2,3
      (14)C]AN. Two hours later, the livers were removed, homogenized, and fractionated
      into subcellular components, and the radioactively labeled proteins were
      separated on SDS-PAGE. One set of labeled proteins was found to be glutathione S
      transferase (GST). Specific labeling of the mu over the alpha class was observed.
      Separation of the GST subunits by HPLC followed by scintillation counting showed
      that AN was selective for subunit rGSTM1. Mass spectral analysis of tryptic
      digests of the GST subunits indicated that the site of labeling was cysteine 86.
      The reason for the high reactivity of cysteine 86 in rGSTM1 was hypothesized to
      be due to its potential interaction with histidine 84, which is unique in this
      subunit.

PMID- 11453726
TI  - Probing the active sites of butyrylcholinesterase and cholesterol esterase with
      isomalathion: conserved stereoselective inactivation of serine hydrolases
      structurally related to acetylcholinesterase.
AB  - Previous work has shown that acetylcholinesterase (AChE), a member of the
      alpha/beta-hydrolase superfamily, is stereoselectively inhibited by the four
      stereoisomers of isomalathion. Recent kinetic and mass spectral data demonstrated
      that a difference in mechanism of inactivation exists for AChE treated with (1R)-
      versus (1S,3S)-stereoisomers. This study sought to determine whether other
      alpha/beta-hydrolases are stereoselectively inhibited by isomalathion and if the
      difference in mechanism of AChE inactivation between (1R)- and (1S,3S)-isomers is
      conserved for other alpha/beta-hydrolases. Bimolecular rate constants of
      inhibition (k(i)) were measured for human and equine butyrylcholinesterase (HBChE
      and EBChE, respectively) and bovine cholesterol esterase (BCholE) with all four
      isomers. Isomalathion isomers inhibited these enzymes with the following order of
      potency: (1R,3R) > (1R,3S) > (1S,3R) > or = (1S,3S). Ratios of k(i) values for
      the most potent to the least potent isomer were 10.5 (HBChE), 11.9 (EBChE), and
      68.6 (BCholE). Rate constants of reactivation (k(3)) were measured for enzyme
      inhibited by isomalathion isomers. HBChE, EBChE, and BCholE inactivated by the
      (1R)-isomers readily reactivated. However, enzymes modified by (1S)-isomalathions
      were refractory toward reactivation, and k(3) values were not significantly
      different from zero for HBChE and BCholE treated with the (1S,3S)-isomer.
      Computer-based docking experiments were performed for BCholE with (1R,3R)- and
      (1S,3S)-enantiomers. Calculated structures predicted a difference in primary
      leaving group: diethyl thiosuccinate for (1R,3R)-isomalathion and thiomethyl for
      the (1S,3S)-isomer. The data demonstrate that the alpha/beta-hydrolases used in
      this study are stereoselectively inhibited by isomalathion. Furthermore, the
      results suggest that the mechanistic shift demonstrated to occur for inhibition
      of AChE by (1R)- versus (1S,3S)-isomers is conserved for butyrylcholinesterase
      and cholesterol esterase.

PMID- 11453727
TI  - Differential regulation of redox responsive transcription factors by the
      nephrocarcinogen 2,3,5-Tris(glutathion-S-yl)hydroquinone.
AB  - 2,3,5-Tris(glutathion-S-yl)hydroquinone [TGHQ] is a potent nephrotoxicant and
      nephrocarcinogen, and induces a spectrum of mutations in human and bacterial
      cells consistent with those attributed to reactive oxygen species (ROS). Studies
      were conducted to determine whether the oxidative stress induced by TGHQ in renal
      proximal tubule epithelial cells (LLC-PK(1)) modulates transcriptional activities
      widely implicated in transformation responses, namely 12-O-tetradecanoyl phorbol
      13-acetate (TPA) responsive element (TRE)- and nuclear factor kappa B (NF-kappaB)
      binding activity. TGHQ increased TRE- and NF-kappaB-binding activity in a
      concentration- and time-dependent manner. Catalase fully inhibited peak TGHQ
      mediated TRE- and NF-kappaB-binding activity. In contrast, although deferoxamine
      fully inhibited TGHQ-mediated TRE-binding activity, it had only a marginal effect
      on NF-kappaB-binding activity. Collectively, these data indicate that TGHQ
      modulates TRE- and NF-kappaB-binding activity in an ROS-dependent fashion.
      Cycloheximide and actinomycin D fully inhibited TGHQ-mediated TRE-binding
      activity, but in the absence of TGHQ increased NF-kappaB-binding activity.
      Although protein kinase C (PKC) is widely implicated in stress response
      signaling, pretreatment of cells with PKC inhibitors (H-89, calphostin C) did not
      modulate TGHQ-mediated DNA-binding activities. In contrast, pretreatment of cells
      with (PD098059), a mitogen activated protein kinase kinase (MEK) inhibitor,
      markedly reduced TGHQ-mediated TRE-binding activity, but enhanced TGHQ-mediated
      NF-kappaB-binding activity. We conclude that TGHQ-mediated TRE- and NF-kappaB
      binding activities are ROS-dependent. Although there is a common requirement for
      hydrogen peroxide (H(2)O(2)) in the regulation of these DNA-binding activities,
      there appears to be divergent regulation after H(2)O(2) generation in renal
      epithelial cells.

PMID- 11453728
TI  - Elucidation of reaction scheme describing malondialdehyde-acetaldehyde-protein
      adduct formation.
AB  - Malondialdehyde and acetaldehyde react together with proteins and form hybrid
      protein conjugates designated as MAA adducts, which have been detected in livers
      of ethanol-fed animals. Our previous studies have shown that MAA adducts are
      comprised of two distinct products. One adduct is composed of two molecules of
      malondialdehyde and one molecule of acetaldehyde and was identified as the 4
      methyl-1,4-dihydropyridine-3,5-dicarbaldehyde derivative of an amino group (MDHDC
      adduct). The other adduct is a 1:1 adduct of malondialdehyde and acetaldehyde and
      was identified as the 2-formyl-3-(alkylamino)butanal derivative of an amino group
      (FAAB adduct). In this study, information on the mechanism of MAA adduct
      formation was obtained, focusing on whether the FAAB adduct serves as a precursor
      for the MDHDC adduct. Upon the basis of chemical analysis and NMR spectroscopy,
      two initial reaction steps appear to be a prerequisite for MDHDC formation. One
      step involves the reaction of one molecule of malondialdehyde and one of
      acetaldehyde with an amino group of a protein to form the FAAB product, while the
      other step involves the generation of a malondialdehyde-enamine. It appears that
      generation of the MDHDC adduct requires the FAAB moiety to be transferred to the
      nitrogen of the MDA-enamine. For efficient reaction of FAAB with the enamine to
      take place, additional experiments indicated that these two intermediates likely
      must be in positions on the protein of close proximity to each other. Further
      studies showed that the incubation of liver proteins from ethanol-fed rats with
      MDA resulted in a marked generation of MDHDC adducts, indicating the presence of
      a pool of FAAB adducts in the liver of ethanol-fed animals. Overall, these
      findings show that MDHDC-protein adduct formation occurs via the reaction of the
      FAAB moiety with a malondialdehyde-enamine, and further suggest that a similar
      mechanism may be operative in vivo in the liver during prolonged ethanol
      consumption.

PMID- 11453729
TI  - N-methylcarbamoylated valine of hemoglobin in humans after exposure to N,N
      dimethylformamide: evidence for the formation of methyl isocyanate?
AB  - N,N-Dimethylformamide (DMF) is reported to cause testicular germ-cell tumors in
      exposed workers. The reports, however, are not in line with results obtained in
      animal and in vitro experiments, where DMF was shown not to be mutagenic and also
      not to be carcinogenic. Considerable interest raised on the formation of a
      reactive intermediate, presumably methyl isocyanate (MIC), during metabolism of
      DMF in humans over the last years. We report the formation of N
      methylcarbamoylated valine of hemoglobin (Hb) in blood samples from workers
      exposed to DMF in the polyacrylic fiber industry. N-Methylcarbamoylated Hb was
      formed by the reaction of MIC with Hb. For this purpose, Hb adducts were
      monitored by means of a modified Edman degradation involving the release of the N
      terminal valine adduct in form of 3-methyl-5-isopropylhydantoin (MIH). For
      internal standardization of the method, 3-ethyl-5-isopropylhydantoin (EIH) was
      used. Separation and analysis of MIH and EIH were carried out by gas
      chromatography and mass spectrometry with electron impact ionization (GC/EI-MS).
      Hb adducts in form of MIH were quantified in blood samples from exposed persons
      in concentrations between 26.1 and 412.0 nmol of MIH/g of globin. The observed
      adducts were proven to be identical to those derived from the in situ reaction
      between Hb and MIC. Taken together with the fact that only N-methylcarbamoylated
      Hb can undergo ring closure to the corresponding hydantoin, the reaction is
      indirect evidence for the occurrence of MIC in vivo. The formation of MIC
      directly in the cell and its possible distribution through the human body may
      lead to critical effects after exposure to DMF. Adducts were determined not to be
      totally specific for exposure to DMF since an identical adduct was also found in
      blood samples from the general population. However, concentrations were lower by
      a factor of about 100. The sources for background adducts are currently unknown.

PMID- 11453730
TI  - Catechin metabolism: glutathione conjugate formation catalyzed by tyrosinase,
      peroxidase, and cytochrome p450.
AB  - The metabolic pathways of dietary flavonoids are still largely unknown. In the
      present work, mass spectrometry and UV-vis spectroscopy studies were used to show
      that the naturally occurring flavonoid catechin underwent enzymatic oxidation by
      tyrosinase in the presence of glutathione (GSH) to form mono-, bi-, and tri
      glutathione conjugates of catechin and mono- and bi-glutathione conjugates of a
      catechin dimer. A hydroxylated catechin adduct was also detected. Using UV
      spectroscopy, it was shown that the catechol B-ring of catechin was oxidized by
      tyrosinase to form an o-quinone which could be reduced back to catechin with
      potassium borohydride or reacted with GSH to form glutathione conjugates. The
      catechin-glutathione conjugates formed had much lower distribution coefficient
      values than catechin itself. When peroxidase and hydrogen peroxide were used
      instead of tyrosinase, only mono-glutathione conjugates were formed but not bi
      glutathione conjugates or hydroxylated adducts. (1)H NMR evidence showed that
      three different mono-glutathione conjugates on ring B of catechin were formed by
      peroxidase and hydrogen peroxide. Rat liver microsomes and NADPH or cumene
      hydroperoxide also catalyzed catechin-glutathione conjugate formation which was
      prevented by benzylimidazole, a P450 2E1 inhibitor. Catechin cytotoxicity toward
      isolated hepatocytes was also markedly enhanced by hydrogen peroxide or cumene
      hydroperoxide and was prevented by benzylimidazole, suggesting that catechin
      could be metabolically activated by P450 peroxidase activity to form cytotoxic
      quinoid species.

PMID- 11453731
TI  - Induction of hepatic 8-oxo-deoxyguanosine adducts by 2,3,7,8-tetrachlorodibenzo-p
      dioxin in Sprague-Dawley rats is female-specific and estrogen-dependent.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a hepatocarcinogen that induces sex
      specific hepatic neoplastic alterations in female, but not male, rats. It has
      been hypothesized that TCDD-induced alterations in estrogen metabolism lead to
      increased generation of reactive oxygen species. The resulting oxidative damage
      to DNA may contribute to TCDD-induced tumor promotion and hepatocarcinogenesis.
      This hypothesis is supported by previous observations of increased 8-oxo
      deoxyguanosine (8-oxo-dG) adduct formation in the livers of intact, but not
      ovariectomized (OVX), rats following chronic exposure to TCDD. The aim of the
      current study was to more clearly define the roles of hormonal regulation,
      gender, dose-response, and exposure duration in TCDD induction of 8-oxo-dG
      adducts. Diethylnitrosamine (DEN)-initiated male and female (both intact and OVX)
      rats were exposed to TCDD in the presence or absence of 17 beta-estradiol.
      Following 30 weeks of exposure, hepatic 8-oxo-dG adduct levels were significantly
      higher in TCDD-treated intact female rats, and TCDD-treated OVX female rats
      receiving supplemental 17 beta-estradiol, when compared to respective corn oil
      vehicle controls. In DEN-initiated female rats exposed to a range of TCDD
      concentrations for 30 weeks, TCDD induced 8-oxo-dG adduct levels in a dose
      dependent manner. However, 8-oxo-dG adduct levels were not altered in TCDD
      treated male or OVX female rats following 30 weeks of exposure. In noninitiated
      female rats, the level of 8-oxo-dG adducts 4 days following a single dose of TCDD
      was not significantly different than in control rats. Additionally, 8-oxo-dG
      adduct formation was not affected by exposure to TCDD for 20 weeks in intact
      female rats. These data suggest that the induction of 8-oxo-dG adduct levels by
      TCDD is likely a response to chronic oxidative imbalance. These studies provide
      strong evidence that the induction of 8-oxo-dG by TCDD occurs via a chronic, sex
      specific, estrogen-dependent mechanism.

PMID- 11453732
TI  - Stable expression of rat dihydrodiol dehydrogenase (AKR1C9) in human breast MCF-7
      cells results in the formation of PAH-o-quinones and enzyme mediated cell death.
AB  - Dihydrodiol dehydrogenase members of the aldo-keto reductase (AKR) superfamily
      have been implicated in the metabolic activation of PAH trans-dihydrodiols
      because they convert these proximate carcinogens to reactive and redox-active o
      quinones. In this study, rat liver 3alpha-hydroxysteroid/dihydrodiol
      dehydrogenase (AKR1C9) was stably transfected into human breast carcinoma (MCF-7)
      cells, which represent a null-environment for AKR expression, to detect the
      formation of PAH o-quinones in a cellular context and the cellular consequences
      of o-quinone formation. The heterologous transfected cells expressed AKR1C9 mRNA
      and protein. Immunotitration of the enzyme activity indicated that the expressed
      protein constituted 1.0% of the soluble protein. The specific activity of the
      expressed enzyme was also comparable to that observed in rat liver cytosol. The
      transfectants were found to convert (+/-)-trans-7,8-dihydroxy-7,8
      dihydrobenzo[a]pyrene (B[a]P-7,8-diol) to benzo[a]pyrene-7,8-dione (BPQ). The
      identity of this metabolite was confirmed by co-chromatography and by UV-Vis
      diode-array spectrometry. This conversion was not evident in mock-transfected
      cells. The cytotoxic consequences of BPQ formation was also examined.
      Transfectants exposed to 1 microM B[a]P-7,8-diol revealed that cytotoxicity, as
      measured by lactate dehydrogenase (LDH) release, occurred over the time course of
      o-quinone formation leading to 77% of the cellular LDH being released by 16 h.
      AKR1C9 inhibitors blocked the B[a]P-7,8-diol dependent cytotoxicity indicating
      that it was mediated by the enzymatically formed BPQ. These data indicate that
      high stable constitutive expression of AKR1C9 will result in B[a]P-7,8-diol
      mediated cytotoxicity due to the formation of unconjugated BPQ.

PMID- 11453733
TI  - Serotonergic neurotoxicity of 3,4-(+/-)-methylenedioxyamphetamine and 3,4-(+/-)
      methylendioxymethamphetamine (ecstasy) is potentiated by inhibition of gamma
      glutamyl transpeptidase.
AB  - Reactive metabolites play an important role in 3,4-(+/-)
      methylenedioxyamphetamine (MDA) and 3,4-(+/-)-methylenedioxymethamphetamine
      (MDMA; ecstasy)-mediated serotonergic neurotoxicity, although the specific
      identity of such metabolites remains unclear. 5-(Glutathion-S-yl)-alpha
      methyldopamine (5-GSyl-alpha-MeDA) is a serotonergic neurotoxicant found in the
      bile of MDA-treated rats. The brain uptake of 5-GSyl-alpha-MeDA is decreased by
      glutathione (GSH), but sharply increases in animals pretreated with acivicin, an
      inhibitor of gamma-glutamyl transpeptidase (gamma-GT) suggesting competition
      between intact 5-GSyl-alpha-MeDA and GSH for the putative GSH transporter. gamma
      GT is enriched in blood-brain barrier endothelial cells and is the only enzyme
      known to cleave the gamma-glutamyl bond of GSH. We now show that pretreatment of
      rats with acivicin (18 mg/kg, ip) inhibits brain microvessel endothelial gamma-GT
      activity by 60%, and potentiates MDA- and MDMA-mediated depletions in serotonin
      (5-HT) and 5-hydroxylindole acidic acid (5-HIAA) concentrations in brain regions
      enriched in 5-HT nerve terminal axons (striatum, cortex, hippocampus, and
      hypothalamus). In addition, glial fibrillary acidic protein (GFAP) expression
      increases in the striatum of acivicin and MDA (10 mg/kg) treated rats, but
      remains unchanged in animals treated with just MDA (10 mg/kg). Inhibition of
      endothelial cell gamma-GT at the blood-brain barrier likely enhances the uptake
      into brain of thioether metabolites of MDA and MDMA, such as 5-(glutathion-S-yl)
      alpha-MeDA and 2,5-bis-(glutathion-S-yl)-alpha-MeDA, by increasing the pool of
      thioether conjugates available for uptake via the intact GSH transporter. The
      data indicate that thioether metabolites of MDA and MDMA contribute to the
      serotonergic neurotoxicity observed following peripheral administration of these
      drugs.

PMID- 11453734
TI  - trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodi- benz[a,j]acridine
      involvement in dibenz[a,j]acridine DNA adduct formation in mouse skin consistent
      with Ha-ras mutation patterns in tumors.
AB  - Dibenz[a,j]acridine (DBA), is a N-heteropolycyclic aromatic environmental
      carcinogen found in complex combustion mixtures. The major route of DBA metabolic
      activation is reportedly through the trans-3,4-dihydroxy-3,4-dihydroDBA (DBA-3,4
      DHD). The present studies were undertaken to determine the role of trans-3,4
      dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydroDBA (DBADE) in DBA activation
      pathway(s), the DNA bases involved in the binding of DBA to DNA, and whether the
      adducts produced are consistent with the mutation pattern in the Ha-ras gene. DBA
      (300 microg) or 50 microg synthesized (+/-)-DBADE was applied to the back of
      female Hsd:ICR(Br) mice. The mice were sacrificed 48 h later, and skin DNA was
      isolated, hydrolyzed, and analyzed with (32)P-postlabeling. Of the four adducts
      produced in vivo, adduct 1 was the major adduct for DBA (>50%) and adduct 2 was
      the major adduct for DBADE (89%). After the reaction of (+/-)-DBADE with purine
      nucleotides or calf thymus (CT) DNA in vitro, 100% of the DBADE-2'-dAMP adducts
      and 94% of DBADE-CT DNA adducts were chromatographically identical on TLC with
      adduct 2 and 86% of the DBADE-2'-dGMP adducts were chromatographically consistent
      with adduct 1 by (32)P-postlabeling. Papillomas were induced on the backs of mice
      by a single application of 0.2 micromol of DBA followed by twice-weekly
      application of 12-o-tetra-decanoylphorbol-13-acetate (TPA, 2 microg) for 24-26
      weeks. Skin carcinomas were induced by twice weekly applications of DBA (0.1
      micromol) on the backs of mice. A to T and G to T transversions were found in
      codons 12, 13, and 61 of the Ha-ras gene in the treated mouse skin carcinoma and
      papilloma DNA. The mutational spectra in the Ha-ras gene are consistent with the
      DNA binding of DBA to dG or dA in vivo. Thus, this research has indicated that
      DBADE plays an important role in DBA metabolic activation and DNA binding in
      mouse skin, and an alternative pathway through a bis-dihydrodiol-epoxide of DBA
      may also be involved.

PMID- 11453735
TI  - Air pollution particles mediated oxidative DNA base damage in a cell free system
      and in human airway epithelial cells in relation to particulate metal content and
      bioreactivity.
AB  - Epidemiological studies demonstrate an association between increased human
      morbidity and mortality with exposure to air pollution particulate matter. We
      hypothesized that such effects may be associated with the ability of the
      particles to mediate generation of reactive oxygen species (ROS), either
      directly, via interaction with ambient oxygen or indirectly through initiation of
      an oxidative burst in phagocytes. To test this hypothesis, we determined 8-oxo-dG
      formation as a measure of direct generation of ROS, in response to particulate
      exposures to 2'-deoxyguanosine (dG), free and in calf thymus DNA in aerated
      solutions as the target molecule and cell culture, to assess the relationship
      between induction of oxidative damage, particulate metal content and metal
      bioreactivity. The HPLC-ECD technique was employed for separation and
      quantification of 8-oxo-dG, the most widely recognized marker of DNA oxidation.
      Particles used in this study include: Arizona desert dust (AZDD), coal fly ash
      (CFA and ECFA), oil fly ash (OFA and ROFA), and ambient air [SRM 1649 and
      Dusseldorf (DUSS), Germany]. The major difference between these particles is the
      concentration of water-soluble metals. The fly ash particulates OFA and ROFA
      showed a significant dose-dependent increase in dG hydroxylation to 8-oxo-dG
      formation over the control dG (p < 0.05), with yields 0.03 and 1.25% at the
      highest particulate concentration (1 mg/mL). Metal ion chelators and DMSO, a
      hydroxyl radical scavenger, inhibited this hydroxylation. In contrast, desert
      dust, coal fly ash and urban air particles induced 8-oxo-dG with yields ranging
      from 0.003 to 0.006%, respectively, with levels unaffected by pretreatment of the
      particles with metal ion chelators or addition of DMSO to the incubation mixture.
      When calf thymus DNA was used as a substrate, all the particles induced 8-oxo-dG
      in a pattern similar to that observed for dG hydroxylation, but with relatively
      less yield. Treatment of the particles with metal ion chelator before reacting
      with DNA or addition of catalase in the incubation mixture, suppressed 8-oxo-dG
      formation significantly (p < 0.05) in oil-derived fly ash particles only. To
      determine whether the oxidative responses of these particulates as shown in cell
      free systems were consistent with responses using a more biologically relevant
      environment, human airway epithelial cells were treated with the particulates and
      induction of 8-oxo-dG was determined. All particles induced 8-oxo-dG in the DNA
      of cells above culture control, except CFA. Cells exposed to 10-400 mg/mL of ROFA
      for 2 h induced a dose-dependent increase in 8-oxo-dG formation. Treatment of
      ROFA with metal ion chelator attenuated these effects. Overall, damage
      enhancement by particulates in dG, calf thymus, and cellular DNA as determined by
      8-oxo-dG formation under aerobic conditions is consistent with the concentration
      of water-soluble, not the total metal content of the particle.

PMID- 11453736
TI  - Resolution of alpha-hydroxytamoxifen; R-isomer forms more DNA adducts in rat
      liver cells.
AB  - The genotoxic tamoxifen metabolite alpha-hydroxytamoxifen has been resolved into
      R- and S-enantiomers. This was achieved by preparing its ester with S-camphanic
      acid, chromatographic separation into two diastereoisomers, and hydrolysis to
      give (+)- and (-)-alpha-hydroxytamoxifen. The configuration of the (-)-isomer was
      shown to be S- by degradation of an ester to a derivative of (-)-2-hydroxy-1
      phenyl-1-propanone, which has already been shown to have S-configuration.
      Metabolism of tamoxifen by rat liver microsomes gave equal amounts of the two
      enantiomers. They have the same chemical properties but, on treatment of rat
      hepatocytes in culture, R-(+)-alpha-hydroxytamoxifen gave at least eight times as
      many DNA adducts as the S-(-)-isomer.

PMID- 11453737
TI  - Mutagenesis by O(6)-methyl-, O(6)-ethyl-, and O(6)-benzylguanine and O(4)
      methylthymine in human cells: effects of O(6)-alkylguanine-DNA alkyltransferase
      and mismatch repair.
AB  - Double-stranded and gapped shuttle vectors were used to study mutagenesis in
      human cells by O(6)-methyl (m(6)G)-, O(6)-ethyl (e(6)G)-, and O(6)-benzylguanine
      (b(6)G), and O(4)-methylthymine (m(4)T) when these bases were incorporated site
      specifically in the ATG initiation codon of a lacZ' gene. Vectors were
      transfected into either human kidney cells (293) or colon tumor cells (SO) or
      into mismatch repair defective human colon tumor cells (H6 and LoVo). Cellular
      O(6)-alkylguanine-DNA alkyltransferase (alkyltransferase) was optionally
      inactivated by treating cells with O(6)-benzylguanine prior to transfection. In
      alkyltransferase competent cells, the mutagenicity of all the modified bases was
      substantially higher in gapped plasmids than in double-stranded plasmids.
      Alkyltransferase inactivation increased mutagenesis by the three O(6)-substituted
      guanines in both double-stranded and gapped plasmids but did not affect m(4)T
      mutagenesis. In the absence of alkyltransferase, mutagenesis by m(6)G and to a
      lesser extent e(6)G in double-stranded vectors was higher in the mismatch repair
      defective H6 and LoVo cells than in SO or 293 cells indicating that e(6)G as well
      as m(6)G were subject to mismatch repair processing in these cells. The level of
      mutagenesis by m(4)T and b(6)G was not affected by mismatch repair status. When
      incorporated in gapped plasmids and in the absence of alkyltransferase, the order
      of mutagenicity for the modified bases was m(4)T > e(6)G congruent with m(6)G >
      b(6)G. The O(6)-substituted guanines primarily produced G-->A transitions while
      m(4)T primarily produced T-->C transitions. However, m(4)T also produced a
      significant number of T-->A transversion mutations in addition to T-->C
      transitions in mismatch repair deficient LoVo cells.

PMID- 11453738
TI  - Regioselective differences in C(8)- and N-oxidation of 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline by human and rat liver microsomes and
      cytochromes P450 1A2.
AB  - The metabolism of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
      (MeIQx) was investigated with human and rat liver microsomes, recombinant human
      cytochrome P450 1A2 (P450 1A2) expressed in Escherichia coli cells, and rat P450
      1A2. Human liver microsomes and human P450 1A2 catalyzed the oxidation of the
      exocyclic amine group of MeIQx to form the genotoxic product 2-(hydroxyamino)-3,8
      dimethylimidazo[4,5-f]quinoxaline (HONH-MeIQx). Human P450 1A2 also catalyzed the
      oxidation of C(8)-methyl group of MeIQx to form 2-amino-(8-hydroxymethyl)-3
      methylimidazo[4,5-f]quinoxaline (8-CH(2)OH-IQx), 2-amino-3-methylimidazo[4,5
      f]quinoxaline-8-carbaldehyde (IQx-8-CHO), and 2-amino-3-methylimidazo[4,5
      f]quinoxaline-8-carboxylic acid (IQx-8-COOH). Thus, chemically stable C(8)
      oxidation products of MeIQx may be useful biomarkers of P450 1A2 activity in
      humans. Rat liver microsomes were 10-15-fold less active than the human
      counterpart at both N-oxidation and C(8)-oxidation of MeIQx when expressed as
      nanomoles of product formed per minute per nanomoles of P450 1A2. Differences in
      regioselective oxidation of MeIQx were also observed with human and rat liver
      microsomes and the respective P450 1A2 orthologs. In contrast to human liver
      microsomes and P450 1A2, rat liver microsomes and purified rat P4501A2 were
      unable to catalyze the oxidation of MeIQx to the carboxylic derivative IQx-8
      COOH, an important detoxication product formed in humans. However, rat liver
      microsomes and rat P4501A2, but not human liver microsomes or human P450 1A2,
      extensively catalyzed ring oxidation at the C-5 position of MeIQx to form the
      detoxication product 2-amino-3,8-dimethyl-5-hydroxyimidazo[4,5-f]quinoxaline (5
      HO-MeIQx). There are important differences between human and rat P450 1A2, both
      in catalytic activities and oxidation pathways of MeIQx, that may affect the
      biological activity of this carcinogen and must be considered when assessing
      human health risk.

PMID- 11453739
TI  - Resolving pathways of interaction of covalent inhibitors with the active site of
      acetylcholinesterases: MALDI-TOF/MS analysis of various nerve agent phosphyl
      adducts.
AB  - Understanding reaction pathways of phosphylation, reactivation, and "aging" of
      AChE with toxic organophosphate compounds is both a biochemical and a
      pharmacological challenge. Here we describe experiments which allowed to resolve
      some of the less well understood reaction pathways of phosphylation and "aging"
      of acetylcholinesterase (AChE) involving phosphoroamidates (P-N agents) such as
      tabun or the widely used pesticide methamidophos. Tryptic digests of phosphylated
      AChEs (from human and Torpedo californica), ZipTip peptide fractionation and
      matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF/MS)
      enabled reproducible signal enrichment of the isotopically resolved peaks of
      organophosphoroamidate conjugates of the AChE active site Ser peptides. For tabun
      and its hexadeuterio analogue, we find, as expected, that the two phosphoramidate
      adducts of the active site peptide differ by 6.05 mass units but following aging
      we find that the two corresponding phospho-peptides have identical molecular
      weights. We further show that the aging product of paraoxon-AChE adduct is
      identical to the aging product of the tabun-AChE conjugate. These results
      unequivocally demonstrate that the pathway of aging of tabun adducts of the human
      or the Torpedo californica AChEs proceeds through P-N bond scission. For
      methamidophos, we show that phosphylation of AChE involves elimination of the
      thiomethyl moiety and that the spontaneous reactivation of the resulting
      organophosphate adduct generates the phosphorus free AChE active site Ser
      peptide.

PMID- 11453740
TI  - Liquid chromatography electrospray-mass spectrometry of urinary aflatoxin
      biomarkers: characterization and application to dosimetry and chemoprevention in
      rats.
AB  - A liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS)
      method for the measurement of aflatoxin biomarkers in urine has been developed
      and validated. The two major aflatoxin-DNA adducts formed in rat tissues,
      aflatoxin N(7)-guanine and its imidazole ring opened derivative, 8,9-dihydro-8
      (2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxy-aflatoxin B(1),
      were detected and quantified in urine by the LC-ESI-MS/MS technique. Other
      metabolites derived from the conjugation and/or oxidation of aflatoxin B(1)
      measured in the urine of dosed rats included aflatoxin P(1), aflatoxin P(1)
      glucuronide, aflatoxin Q(1), aflatoxin M(1), 8,9-dihydro-8,9-dihydroxy aflatoxin
      B(1), aflatoxin B(1)-mercapturic acid, the aflatoxin-cysteine glycine adduct
      derived from the aflatoxin-glutathione conjugate, aflatoxin M(1)P(1) and the
      aflatoxin B(1)-dialcohol. For in vivo studies to determine the dosimetry of
      certain aflatoxin metabolites, aflatoxin B(2) was used as an internal standard
      for recovery since this compound is not naturally produced in rats. In the final
      method using the internal standard, the coefficient of variation of six replicate
      analyses of in vivo rat urine samples for aflatoxin N(7)-guanine, aflatoxin B(1)
      mercapturic acid, and aflatoxin M(1) was 12.5, 12.8, and 5.8%, respectively.
      Further, the LC-ESI-MS/MS method to detect aflatoxin N(7)-guanine in in vivo rat
      urine samples was at least 20-fold more sensitive than prior techniques. Using
      the LC-ESI-MS/MS technique, the dosimetry, on a weekly basis, of major urinary
      aflatoxin metabolites was assessed in animals chronically dosed over a 5-week
      period. Of particular importance was the application of this method to determine
      the modulation of levels of urinary aflatoxin metabolites by treatment with
      oltipraz, a chemopreventive agent that can completely ablate aflatoxin
      hepatocarcinogenesis in the rat. After 1 week, oltipraz administration diminished
      urinary aflatoxin N(7)-guanine, aflatoxin B(1)-mercapturic acid and aflatoxin
      M(1) levels by 83, 92, and 82%, respectively. The magnitude of this reduction was
      persistent at the day 14, 21, 28, and 35-day time points with the average
      decrease of aflatoxin N(7)-guanine, aflatoxin B(1)-mercapturic acid and aflatoxin
      M(1) being 73, 92, and 90%, respectively. Importantly, even under circumstances
      where the oltipraz intervention was most efficient in reducing aflatoxin
      metabolite levels, the LC-ESI-MS/MS method was still sensitive enough to detect
      the reduced biomarker content. This outcome has important translational
      implications for the application and analysis of the efficacy of primary and
      secondary prevention interventions in human populations where ambient exposure
      levels are low, but the toxicologic hazards of these exposures remain high.

PMID- 11453741
TI  - Characterization of hydantoin products from one-electron oxidation of 8-oxo-7,8
      dihydroguanosine in a nucleoside model.
AB  - Use of one-electron oxidants such as Na(2)IrCl(6) to oxidize 8-oxo-7,8-dihydro-2'
      deoxyguanosine (OG) residues in oligodeoxynucleotides was previously shown to
      lead to predominant formation of a base lesion of mass M - 10 compared to
      starting material [Duarte et al. (1999) Nucleic Acids Res. 27, 596-502]. To
      thoroughly characterize the structure of this lesion, the oxidation of the
      nucleoside 9-N-(2',3',5'-tri-O-acetyl-beta-D-erythro-pentanosyl)-8-oxo-7,8
      dihydroguanine with one-electron oxidants at pH 2-4 was used as a model for
      duplex DNA oxidation of OG residues. (1)H NMR and H,H COSY NMR studies in CD(3)OD
      along with LC-ESI-MS/MS fragmentation analysis are consistent with the assignment
      of the M - 10 species as a mixture of two pH-dependent equilibrating isomers, a
      guanidinohydantoin (Gh) and an iminoallantoin (Ia) nucleoside, both present as
      mixtures of epimers at the C5 position of the hydantoin ring, i.e., four total
      isomers are formed. The Gh/Ia mixture is formed from hydration and
      decarboxylation of the initially formed intermediate 5-hydroxy-8-oxo-7,8
      dihydroguanosine, a species that is also produced by four-electron oxidation
      (e.g., singlet oxygen) of guanosine. The product mixture can be further oxidized
      to a species designated Ia(ox), a hydrolytically unstable material at pH 7 that
      has been characterized by ESI-MS and (1)H NMR. Competition studies with 8-oxo-7,8
      dihydroadenosine placed the redox potential of Gh/Ia at about 1.0 V vs NHE. These
      studies provide important information concerning the structures of lesions
      obtained when OG, a "hot spot" for oxidative damage, serves as a "hole trap" in
      long-range electron-transfer studies.

PMID- 11453742
TI  - Extraction and isolation of lignin for utilization as a standard to determine
      lignin concentration using the acetyl bromide spectrophotometric method.
AB  - Lignin extracted with acidic dioxane was investigated as a possible standard for
      quantitatively determining lignin content in plant samples using the
      spectrophotometric method employing acetyl bromide. Acidic dioxane lignins were
      analyzed for carbohydrate, total protein, nitrobenzene oxidation products, and UV
      spectral characteristics. Total carbohydrate content of isolated lignins ranged
      from 2.21 to 5.70%, while protein ranged from 0.95 to 6.06% depending upon the
      plant source of the original cell wall sample. Nitrobenzene analysis indicated
      differences in the amount of guaiacyl and syringyl units making up the lignins,
      but this did not alter the UV spectrum of lignin solubilized in acetyl bromide.
      Regression equations developed for the acetyl bromide method using the isolated
      lignins for all the plant samples were similar to each other. Lignin values
      obtained by the acetyl bromide method were similar to the lignin values obtained
      as acid insoluble residues following a Klason lignin procedure.

PMID- 11453743
TI  - Low-resolution gas-phase FT-IR method for the determination of the
      limonene/carvone ratio in supercritical CO2-extracted caraway fruit oils.
AB  - A low-resolution gas-phase FT-IR method for the fast analysis of supercritical
      CO2-extracted caraway fruit oils has been developed. The limonene/carvone ratio
      of extraction product was determined within seconds, yielding a coefficient of
      variation of <5% (n = 10). A selection of experimental parameters is discussed on
      the basis of the analysis of 52 extracted samples. GC-FID was used as a reference
      method. A correlation of 0.983 (n = 24) between the two methods was observed.
      This method is suitable for the analysis of a large number of caraway fruit
      extracts due to its speed, repeatability, and minimum sample preparation.

PMID- 11453744
TI  - Determination of sulfamethazine and trimethoprim in liquid feed premixes by HPLC
      and diode array detection, with an analysis of the uncertainty of the analytical
      results.
AB  - Sulfamethazine (SMZ) and trimethoprim (TMP) are antibacterials used in veterinary
      practice. This paper describes a method for their determination in veterinary
      liquid feed premixes that is based on liquid chromatography with diode array
      detection. Gradient elution with methanol and ammonium acetate achieved excellent
      separation of the two analytes within 15 min without any interference from the
      matrix. Absorbance of the column effluent was monitored at 264 nm for SMZ and at
      230 nm for TMP. Detailed analyses of the uncertainties of determinations afford
      estimated expanded uncertainties of, respectively, 0.2 and 0.1 w/v % for typical
      SMZ and TMP concentrations of 10.7 and 2.1 w/v %, respectively. At the lower end
      of the calibrated range of the method, the dominant source of uncertainty is the
      preparation of standards and the construction of the calibration line.

PMID- 11453745
TI  - Potential of semiconductor sensor arrays for the origin authentication of pure
      Valencia orange juices.
AB  - Sensor array is a new method used in aroma analysis. This technique was employed
      for the differentiation of 49 pure Valencia orange juices from 5 different
      origins representative of the main culture areas of citrus according to their
      volatile organic fractions. An experimental design was used to set analytical
      factors, which control the generation of the static headspace; therefore, the
      preliminary optimization of analytical conditions allows the evaluation of the
      potential of such an apparatus in this kind of survey. Results obtained were then
      statistically treated by multivariate analyses such as principal component
      analysis and factorial discriminant analysis. Sensor arrays performed a good
      discrimination of the whole juices in classing them according to the origin of
      Valencia oranges used. A calibration of the sensors was then performed to build a
      database aiming to classify the juices according to the origin of oranges
      involved. New supplementary samples were then analyzed to assess the efficiency
      of the database. This technique coupled with other ones such as high-pressure
      liquid chromatography and gas chromatography may be a new tool for the
      investigation of adulteration detection due to the authentication of the origin
      of raw materials employed in the orange juice processes.

PMID- 11453746
TI  - Analysis by hplc of ryanodine and dehydroryanodine residues on fruits and in
      ryania powdery wood.
AB  - A simple and rapid HPLC method to evaluate residues of the major ryanoids
      (ryanodine and dehydroryanodine) on three fruits (olives, apples, and pears) has
      been developed. The pesticides were extracted from the fruits with hexane and
      acetone solution (1:1, v/v). Cleanup was carried out with aminopropyl-bonded
      silica cartridges. This method is characterized by recovery >75%, precision <11%
      RSD, and sensitivity of 0.020 mg/kg. The method can also be used to determine the
      level of active ingredients in ryania powdery wood.

PMID- 11453747
TI  - White wine with red wine-like properties: increased extraction of grape skin
      polyphenols improves the antioxidant capacity of the derived white wine.
AB  - Lower antioxidant activity in white wines in comparison to red wines lies in the
      low grape-skin-derived polyphenol content. This paper reports the analysis of the
      antioxidant capacities of white wine samples obtained along two different
      processing procedures directed to enrich the wine with polyphenols. White wine
      samples derived from whole squeezed grapes stored for increasing periods of time
      (up to 18 h) contained increasing concentrations of polyphenols (from 0.35 to
      0.55 mmol/L) and, in parallel, exhibited increased capacity to scavenge free
      radicals and to inhibit copper ion-induced low-density lipoprotein (LDL)
      oxidation. However, addition of increasing concentrations of alcohol (up to 18%)
      to the whole squeezed grapes remarkably augmented the extraction of grape skin
      polyphenols into the wine up to 1.25 mmol/L, resulting in an increased capacity
      of the wine to scavenge free radicals and to inhibit LDL oxidation, to an extent
      similar to that of red wine. The extent of LDL oxidation inhibition was directly
      related to the wine polyphenolic content (r = 0.986). It is concluded that
      processing white wine by imposing a short period of grape skin contact in the
      presence of alcohol leads to extraction of grape skin polyphenols and produces
      polyphenol-rich white wine with antioxidant characteristics similar to those of
      red wine.

PMID- 11453748
TI  - Enzyme-assisted extraction of antioxidative phenols from black currant juice
      press residues (Ribes nigrum).
AB  - Enzymatic release of phenolic compounds from pomace remaining from black currant
      (Ribes nigrum) juice production was examined. Treatment with each of the
      commercial pectinolytic enzyme preparations Grindamyl pectinase, Macer8 FJ,
      Macer8 R, and Pectinex BE, as well as treatment with Novozym 89 protease,
      significantly increased plant cell wall breakdown of the pomace. Each of the
      tested enzyme preparations except Grindamyl pectinase also significantly enhanced
      the amount of phenols extracted from the pomace. Macer8 FJ and Macer8 R decreased
      the extraction yields of anthocyanins, whereas Pectinex BE and Novozym 89
      protease showed no effect. A decrease in pomace particle sizes from 500-1000
      microm to <125 microm increased the phenol yields 1.6-5 times. Black currant
      pomace devoid of seeds gave significantly higher yields of phenols than pomace
      with seeds and seedless wine pomace. Four selected black currant pomace extracts
      all exerted a pronounced antioxidant activity against human LDL oxidation in
      vitro when tested at equimolar phenol concentrations of 7.5-10 microM.

PMID- 11453749
TI  - In vitro metabolism of plant lignans: new precursors of mammalian lignans
      enterolactone and enterodiol.
AB  - The metabolism of the plant lignans matairesinol, secoisolariciresinol,
      pinoresinol, syringaresinol, arctigenin, 7-hydroxymatairesinol, isolariciresinol,
      and lariciresinol by human fecal microflora was investigated to study their
      properties as mammalian lignan precursors. The quantitative analyses of lignan
      precursors and the mammalian lignans enterolactone and enterodiol were performed
      by HPLC with coulometric electrode array detector. The metabolic products,
      including mammalian lignans, were characterized as trimethylsilyl derivatives by
      gas chromatography-mass spectrometry. Matairesinol, secoisolariciresinol,
      lariciresinol, and pinoresinol were converted to mammalian lignans only. Several
      metabolites were isolated and tentatively identified as for syringaresinol and
      arctigenin in addition to the mammalian lignans. Metabolites of 7
      hydroxymatairesinol were characterized as enterolactone and 7
      hydroxyenterolactone by comparison with authentic reference compounds. A
      metabolic scheme describing the conversion of the most abundant new mammalian
      lignan precursors, pinoresinol and lariciresinol, is presented.

PMID- 11453750
TI  - Constituents of compositae plants. 2. Triterpene diols, triols, and their 3-o
      fatty acid esters from edible chrysanthemum flower extract and their anti
      inflammatory effects.
AB  - The n-hexane soluble and the nonsaponifiable lipid fractions of the edible flower
      extract of chrysanthemum (Chrysanthemum morifolium) were investigated for
      triterpene diol and triol constituents. These triterpenes occur as the 3-O-fatty
      acid esters in the n-hexane soluble fraction from which 26 new and 6 known fatty
      acid esters were isolated and characterized. From the nonsaponifiable lipid
      fraction, 24 triterpene diols and triols were isolated, of which 3 were new
      compounds: (24S)-25-methoxycycloartane-3beta,24-diol (11), (24S)-25
      methoxycycloartane-3beta,24,28-triol (22), and 22alpha-methoxyfaradiol (23).
      Faradiol (9) and heliantriol C (19), present in the nonsaponifiable lipid
      fraction and as the 3-O-palmitoyl esters in the n-hexane soluble fraction, were
      the most predominant triterpene diol and triol constituents. Fourteen triterpene
      diols and triols and 9 fatty acid esters were evaluated with respect to their
      anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced inflammation in mice. All of the triterpenes examined showed marked
      inhibitory activity, with a 50% inhibitory dose (ID50) of 0.03-1.0 mg/ear, which
      was more inhibitive than quercetin (ID50 = 1.6 mg/ear), a known inhibitor of TPA
      induced inflammation in mice.

PMID- 11453751
TI  - Antioxidant activity of the main bioactive derivatives from oleuropein hydrolysis
      by hyperthermophilic beta-glycosidase.
AB  - The main reaction products obtainable by the hydrolysis of commercially available
      oleuropein by hyperthermophilic beta-glycosidase were purified and structurally
      characterized by UV and 1H and 13C NMR analyses. Their antioxidant activity, in
      particular their capacity to inhibit the fatty acid peroxidation rate, was
      studied. The molecular structures assigned revealed the presence of two elenolic
      acid forms presenting different antioxidant abilities closely correlated to their
      molecular structures, as well as an unstable elenolate which is a rearrangement
      product of the oleuropein aglycon. This molecule, under the reaction conditions
      (pH 7.0, 60 degrees C) required for beta-glycosidase activity, rapidly gives rise
      to 3,4-dihydroxy-phenylethanol (hydroxytyrosol).

PMID- 11453752
TI  - Detection of streptomycin residues in whole milk using an optical
      immunobiosensor.
AB  - The development of an assay for the detection of streptomycin residues in
      pasteurized whole milk using an optical biosensor (Biacore) is reported.
      Streptomycin-adipic hydrazide coupled to bovine thyroglobulin was used to produce
      a sheep polyclonal antibody. The antibody displayed excellent cross-reactivity
      with dihydrostreptomycin (106%). There was no significant cross-reaction with
      other aminoglycosides or common antibiotics. Streptomycin was also immobilized
      onto a CM5 sensor chip to provide a stable, reusable surface. The developed assay
      permitted the direct analysis of whole milk samples ( approximately 3.5% fat)
      without prior centrifugation and defatting. Results were available in 5 min. The
      limit of detection of the assay was determined as 4.1 ng/mL, well below the
      European maximum residue limit (MRL) of 200 ng/mL. Repeatability (or coefficient
      of variation) between runs was determined as 3.5% (100 ng/mL; 0.5 x MRL), 5.7%
      (200 ng/mL; MRL), and 7.6% (400 ng/mL; 2 x MRL).

PMID- 11453753
TI  - Effect of several germination conditions on total P, phytate P, phytase, and acid
      phosphatase activities and inositol phosphate esters in rye and barley.
AB  - Two assays were conducted to study the evolution of rye and barley phosphatases
      (phytase and acid phosphatase) and the degradation of its substrates (inositol
      phosphate esters) during seed germination. In this manner we could obtain a low
      phytate, endogenous phosphatase rich ingredient to be used in animal nutrition.
      In the first assay, the seeds were soaked for 1 and 14 h and germinated for 3 and
      5 days with and without the addition of gibberellic acid (GA3). In the second
      assay, the seeds were soaked for 1 h and germinated for 1, 3, and 5 days with
      GA3. Phytase (up to 5739 and 3151 U x kg(-1)) and acid phosphatase (up to 18288
      and 3151 U x g(-1)) activities, and IP6 (6.09 and 6.01 mg x g(-1)), IP5 (0.48 and
      0.48 mg x g(-1)), and IP4 (0.13 and 0.06 mg x g(-1)) were detected in
      ungerminated rye and barley, respectively. The germination process caused a
      significant increase of Phy and AcPh activities in rye (up to 112 and 213%) and
      barley (up to 212 and 634%) and a reduction in the phytate phosphorus content (up
      to 84 and 58%, respectively). Phytate phosphorus content was affected only by
      soaking time in the case of rye. Finally, during the course of germination, IP6
      and IP5 were rapidly degraded in rye (88 and 79%) and barley (67 and 52%), and
      IP4 was only a short-living intermediate, which was increased during hydrolysis
      and degraded to IP3. In conclusion, a marked increase of Phy and AcPh activities
      in rye and barley with a concomitant decrease in phytate phosphorus content and
      an increase in the content of lower inositol phosphates were observed during the
      rye and barley germination.

PMID- 11453754
TI  - Domestic processing of onion bulbs (Allium cepa) and asparagus spears (Asparagus
      officinalis): effect on flavonol content and antioxidant status.
AB  - Two commonly consumed plant foods, onion bulbs and asparagus spears, were
      subjected to typical domestic processing, including chopping, maceration, and
      boiling. The impact of these processes on flavonol content was assessed. Further,
      the consequences of these processes on the antioxidant capacity of the tissues
      were evaluated with the beta-carotene bleaching method. Chopping significantly
      affected rutin content in asparagus, yielding an 18.5% decrease in 60 min; but in
      onions, quercetin 3,4'-diglucoside (Q(DG)) and quercetin 4'-glucoside (Q(MG))
      were virtually unaffected by chopping. Boiling for 60 min had more severe
      effects, as it caused overall flavonol losses of 20.6 and 43.9% in onions and
      asparagus, respectively. Chopping of tissues did not considerably influence the
      antioxidant capacity, but boiling did provoke notable changes.

PMID- 11453755
TI  - Effect of cooling rate on nucleation behavior of milk fat--sunflower oil blends.
AB  - The effect of cooling rate on the crystallization behavior of mixes of high
      melting milk fat fraction (HMF) and sunflower oil (SFO) was studied by following
      nucleation with laser-polarized turbidimetry. The initial crystals were
      photographed, and their thermal and polymorphic behaviors, as well as chemical
      composition, were investigated by calorimetry, X-ray diffraction, and capillary
      gas chromatography. Activation energies of nucleation were calculated using the
      Fisher-Turnbull equation. Despite small differences in Mettler dropping points
      for different ratios of SFO to HMF, induction times were significantly different
      between samples and were shorter at a slow cooling rate for the same
      supercooling. Rapidly cooled samples required more time at crystallization
      temperature to crystallize than slowly cooled samples because molecular
      organization prior to nuclei formation took place under different conditions.
      Regardless of cooling rate or composition, all crystals were in the beta'
      polymorph. However, morphology, thermal behavior, and chemical composition showed
      differences with cooling rate. Activation free energies of nucleation were of the
      same order of magnitude as those published for hydrogenated SFO.

PMID- 11453756
TI  - Storage temperature effects on blood orange fruit quality.
AB  - Orange fruits of two blood varieties (Tarocco and Moro) were stored at 8 degrees
      C and 22 degrees C for 85 and 106 days, respectively, and analyzed periodically
      for standard quality parameters (total soluble solids, total acidity, ascorbic
      acid, juice yield, and rind color) and sensory influencing parameters
      (anthocyanins, and total and free hydroxycinnamic acids). A decrease in total
      acidity (TA) and juice yield during storage was observed for both cultivars;
      total soluble solids (TSS) increased only in the Tarocco oranges stored at 8
      degrees C. The increase in TSS observed for Tarocco and the simultaneous decrease
      in TA in both varieties resulted in a higher maturity index (TSS/TA) for the two
      cultivars. No loss of vitamin C was noted in Tarocco orange at either
      temperature, whereas a sharp reduction in vitamin C occurred in the first 50 days
      of storage for Moro. A significant increase in anthocyanin content was observed
      in Tarocco and Moro stored at 8 degrees C. Overlong storage induces extensive
      hydrolysis of hydroxycinnamic derivatives to free acids in Moro orange and these,
      in turn, could develop the malodorous vinylphenols.

PMID- 11453757
TI  - Beta-lactoglobulin molten globule induced by high pressure.
AB  - Beta-lactoglobulin (beta-LG) was treated with high hydrostatic pressure (HHP) at
      600 MPa and 50 degrees C for selected times as long as 64 min. The intrinsic
      tryptophan fluorescence of beta-LG indicated that HHP treatment conditions
      induced a conformational change. HHP treatment conditions also promote a 3-fold
      increase in the extrinsic fluorescence of 1-anilinonaphthalene-8-sulfonate and a
      2.6-fold decrease for cis-paraneric acid, suggesting an increase in accessible
      aromatic hydrophobicity and a decrease in aliphatic hydrophobicity. Far
      ultraviolet circular dichroism (CD) spectra reveal that the secondary structure
      of beta-LG converts from native beta-sheets to non-native alpha-helices following
      HHP treatment, whereas near-ultraviolet CD spectra reveal that the native
      tertiary structure of beta-LG essentially disappears. Urea titrations reveal that
      native beta-LG unfolds cooperatively, but the pressure-treated molecule unfolds
      noncooperatively. The noncooperative state is stable for 3 months at 5 degrees C.
      The nonaccessible free thiol group of cysteine121 in native beta-LG became
      reactive to Ellman's reagent after adequate HHP treatment. Gel electrophoresis
      with and without beta-mercaptoethanol provided evidence that the exposed thiol
      group was lost concomitant with the formation of S-S-linked beta-LG dimers.
      Overall, these results suggest that HHP treatments induce beta-LG into
      hydrophobic molten globule structures that remain stable for at least 3 months.

PMID- 11453758
TI  - Changes in the aroma of a strawberry drink during storage.
AB  - The flavor of a commercially available strawberry drink was investigated with
      special regard to the changes of the sensory properties during the shelf life of
      the product. The experiments were performed using gas chromatographic methods
      after liquid-liquid extraction and after solid-phase microextraction of the
      headspace. A trained sensory test panel was used to substantiate the results from
      instrumental analyses. The relative concentrations of several compounds were
      followed over a storage period of six weeks at elevated temperature (37 degrees
      C), which corresponds to about 12 months storage at room temperature. Significant
      concentration changes of several flavor compounds were determined after a short
      storage time. These results correlate highly with changes in the aroma observed
      by the sensory test panel. Further on, changes in the sensorial relevance of
      aroma active compounds were monitored by comparative aroma extract dilution
      analysis of extracts of the fresh product and the product at the end of the
      declared shelf-life time. The results showed a significant decrease in flavor
      dilution factors of compounds with characteristic fruity attributes.

PMID- 11453759
TI  - Carotenoid content, physicochemical, and sensory qualities of deep-fried carrot
      chips as affected by dehydration/rehydration, antioxidant, and fermentation.
AB  - Carrot slices were subjected to one of the following experiments prior to deep
      frying: (A) dehydration/rehydration, (B) soaking in different antioxidants, and
      (C) fermentation with/without blanching. There were no significant differences (P
      > or = 0.05) in carotenoid contents among carrot chips treated with/without
      dehydration. Soaking in sodium metabisulfite resulted in the highest carotenoid
      content and lightness (L), redness (a), and yellowness (b) values among the
      antioxidant treatments. Fermentation without blanching significantly decreased (P
      < 0.05) carotenoid content, vitamin A activity, and fat content. Dehydration and
      fermentation with blanching significantly increased (P < 0.05) the lightness (L),
      redness (a), and yellowness (b) values of the chips. Dehydration/rehydration, but
      not antioxidant and fermentation, significantly decreased (P < 0.05) the water
      activity of the chips. The textural values of carrot chips prepared using sodium
      metabisulfite, without dehydration and without fermentation, were the lowest
      among other treatments which suggests the crispiest. Carrot chips prepared using
      sodium metabisulfite, without dehydration and without fermentation, had the
      highest carotenoid content and retention, and the highest overall acceptability
      score.

PMID- 11453760
TI  - Divalent cation interactions with oligogalacturonides.
AB  - The conformational properties of high and low molecular weight galacturonides
      were investigated in relation to the ability of oligomers with degree of
      polymerization >10 to act as elicitors of plant defense mechanisms. Oligomers
      from polygalacturonate were obtained by means of enzymatic hydrolysis. Two
      fractions exhibiting high and low average degrees of polymerization were isolated
      by solvent fractionation and characterized by means of electrospray mass
      spectrometry. The conformational behaviors of the two fractions were investigated
      in the presence of different divalent cations using circular dichroism. Calcium,
      copper, and zinc ions were able to induce a conformational transition in both
      fractions. When in the presence of the high molecular weight fraction, copper and
      zinc ions were much more effective than calcium ions, whereas the efficiency was
      much reduced with low molecular weight oligomers.

PMID- 11453761
TI  - Phenols in citrus peel byproducts. Concentrations of hydroxycinnamates and
      polymethoxylated flavones in citrus peel molasses.
AB  - In addition to the main flavanone glycosides (i.e., hesperidin and naringin) in
      citrus peel, polymethoxylated flavones and numerous hydroxycinnamates also occur
      and are major phenolic constituents of the molasses byproduct generated from
      fruit processing. Although a small number of the hydroxycinnamates in citrus
      occur as amides, most occur as esters and are susceptible to alkaline hydrolysis.
      This susceptibility to alkaline hydrolysis was used in measuring the
      concentrations of hydroxycinnamates in citrus peel molasses. The highest
      concentrations of hydroxycinnamates occurred in molasses of orange [C. sinensis
      (L.) Osbeck] and tangerine (C. reticulata Blanco.) compared to grapefruit (C.
      paradisi Macf.) and lemon [C. limon (L.) Burm.]. Concentrations of two phenolic
      glucosides, phlorin (phloroglucinol-beta-O-glucoside) and coniferin (coniferyl
      alcohol-4-beta-O-glucoside), were also measured. Measurements of the
      polymethoxylated flavones in molasses from several tangerine and orange varieties
      showed that these compounds occurred in the highest amounts in Dancy tangerine,
      whereas samples from two other tangerine molasses contained significantly lower
      levels, similar to those in the molasses samples from late- and early/mid-season
      oranges.

PMID- 11453762
TI  - Flavonol content varies among black currant cultivars.
AB  - Flavonoids and related plant compounds in fruits and vegetables are of particular
      importance as they have been found to possess antioxidant and free radical
      scavenging activity. The HPLC-based quantitative procedure, with improved
      extraction and hydrolysis, was used to analyze the content of the flavonols
      quercetin, myricetin, and kaempferol in 10 black currant cultivars from organic
      farms and in 5 cultivars from conventional farms. Myricetin was the most abundant
      flavonol, and its amount varied significantly among cultivars, from 8.9 to 24.5
      mg x 100 g(-1) (fresh weight). The quercetin levels in black currant also varied
      widely among the cultivars, from 5.2 to 12.2 mg x 100 g(-1). The kaempferol
      levels in black currant cultivars were low, ranging from 0.9 to 2.3 mg x 100 g(
      1). The sum of these major flavonols varied widely among black currant cultivars.
      No consistent differences in the contents of flavonols were found between the
      same black currant cultivars grown in organic and conventional ways. The high
      variability in the levels of flavonols in different cultivars offers possible
      avenues for identifying and selecting cultivars rich in certain flavonols for the
      special production of berries for industrial use.

PMID- 11453763
TI  - Sesquiterpene, alkene, and alkane hydrocarbons in virgin olive oils of different
      varieties and geographical origins.
AB  - The hydrocarbon fraction of 30 virgin olive oils was analyzed, focusing in
      particular on the sesquiterpenes. The oil samples were of different geographical
      origins and obtained from different olive varieties. The hydrocarbon fraction was
      isolated by silica gel column chromatography of the unsaponifiable fraction of
      the oils. The sesquiterpene hydrocarbons were then fractionated, on the basis of
      their degree of unsaturation, by AgNO3 TLC and silica gel AgNO3 column
      chromatography. The composition of the sesquiterpenes was more complex than
      previously reported. Among the 31 sesquiterpenes detected, 24 have been
      tentatively identified, by comparison of the linear retention indices on two
      capillary columns of different polarities and mass spectra with those reported in
      the literature. The total concentration of the sesquiterpenes in the oils
      analyzed ranged from about 2 to 37 ppm. Among the sesquiterpenes the more
      abundant were alpha-farnesene, alpha-copaene, eremophyllene, and alpha-muurolene.
      The alkenes present in the hydrocarbon fraction were isolated by TLC AgNO3 and
      characterized by GC-MS of their dimethyl disulfide derivatives. The series of n
      Delta9-alkenes from C22 to C27, 8-heptadecene, and 6,10-dimethyl-1-undecene were
      detected. Among the n-alkanes, those with an odd number of carbon atoms
      predominated in all of the analyzed oils, the most common being C23, C25, C27,
      and C29. The concentration of the n-alkenes ranged from about 0.5 to 2 ppm,
      whereas for the n-alkanes the range was from 30 to 177 ppm.

PMID- 11453764
TI  - Terrestrial field dissipation of diclosulam at four sites in the United States.
AB  - The soil dissipation of diclosulam was studied using 14C-labeled and
      nonradiolabeled material in Mississippi, North Carolina, Georgia, and Illinois
      between 1994 and 1997. The test substance was preemergence broadcast applied at
      target rates of 35 and 37 g ai x ha(-1) for the 14C-labeled and the
      nonradiolabeled studies, respectively. The degradation of diclosulam was rapid
      with half-lives ranging from 13 to 43 days at the four sites. Rapid degradation
      rates and the increasing sorption to soil over time resulted in low persistence
      and mobility of this compound. Metabolite formation and dissipation in the field
      reflected observations of photolysis, hydrolysis, and aerobic soil metabolism
      studies in the laboratory. The rapid field dissipation rates, metabolite
      formation patterns, and sorption characteristics obtained in these field studies
      were consistent with the laboratory data generated for diclosulam, and reflect
      the multiple concurrent degradation mechanisms occurring in the field.

PMID- 11453765
TI  - Monitoring the preventive effect of hydrogen peroxide and gamma-radiation of
      aflatoxicosis in growing rabbits and the effect of cooking on aflatoxin residues.
AB  - The objective of the present study was the prevention of aflatoxicosis of growing
      rabbits fed aflatoxin (AF)-contaminated diet (833 microg of aflatoxins/kg) using
      5% hydrogen peroxide (H2O2) and gamma-radiation at a dose level of 500 krad (5
      kGy) and fed to growing rabbits. A total of 24 New Zealand white rabbits were
      divided into three groups. The experimental diets included AF-contaminated diet;
      AF-decontaminated diet, and AF-free diet (control). The obtained data showed
      significant reduction (p < 0.05) in live body weight and body weight gain of
      rabbits that fed on AF-contaminated diet as well as AF-decontaminated diet
      relative to control. There were no differences in feed consumption among the
      three groups; feed efficiency reduced significantly for AF-contaminated and AF
      decontaminated groups. Mortality percentage was 25% for AF-contaminated and AF
      decontaminated groups. Relative weight of the liver increased in animals fed AF
      contaminated and AF-decontaminated diets, whereas the relative weight of kidneys
      decreased for both. There was no difference in total protein, but the levels of
      albumin and globulin were altered in rabbits receiving AF-contaminated diet.
      Serum enzymes (alanine amino transferase and aspartate amino transferase)
      activity increased significantly in rabbits that received AF-contaminated as well
      as AF-decontaminated diets. Histopathological examination revealed particularly
      alteration in liver and kidneys of rabbits fed AF-decontaminated diet. Results
      showed that the percentage of aflatoxin reduction ranged between 67 and 80% in
      boiled liver and between 79 and 90.5% in fried liver, whereas complete reduction
      in AF was found after boiling followed by frying. These findings indicate that
      the use of H2O2 and gamma-radiation for the destruction of aflatoxins in
      contaminated diet induces adverse effects in the animals.

PMID- 11453766
TI  - Influence of rhamnolipids and triton X-100 on the biodegradation of three
      pesticides in aqueous phase and soil slurries.
AB  - The effect of surfactants on the biodegradation of trifluralin and atrazine (by
      Streptomyces PS1/5) and coumaphos (by degrading consortia from a contaminated
      cattle dip) in liquid cultures and soil slurries was tested at different
      concentrations of a rhamnolipid mixture (Rh-mix) and Triton X-100 (TX-100). The
      extent of trifluralin biodegradation in liquid culture was improved at high
      concentrations of both surfactants. The extent of atrazine degradation dropped in
      the presence of either surfactant. Coumaphos biodegradation improved slightly at
      Rh-mix dosages >3000 microM; however, it was readily inhibited by TX-100 at
      amounts above the critical micelle concentration. In soil slurries, the extent of
      both trifluralin and atrazine biodegradation was higher in Hagerstown A (HTA)
      soil than in Hagerstown B (HTB) soil and was not significantly affected by the
      presence of either surfactant. The onset of trifluralin biodegradation was
      retarded at higher concentrations of surfactants. In the absence of surfactant,
      up to 98% of coumaphos in both soil slurries was transformed. At increasing
      dosages of Rh-mix, the onset of coumaphos biodegradation was retarded, but the
      removal efficiency of the pesticide increased. Rh-mix and TX-100 depletion was
      observed during Streptomyces PS1/5 growth in liquid cultures. Rh-mix
      concentration also decreased during coumaphos biodegradation, whereas TX-100
      concentration was not affected. These results suggest that surfactants, added for
      the purpose of increasing the apparent water solubility of hydrophobic organic
      compounds, may have unintended effects on both the rate and extent of
      biodegradation of the target compounds if the surfactants can also be degraded by
      the microorganisms in the system.

PMID- 11453767
TI  - Change in the flavor of black tea drink during heat processing.
AB  - Heat processing during canning is responsible for the change in flavor of black
      tea infusion. The quantitative change in the volatile components of the black tea
      infusion during heat processing is not sufficient for explaining the sensory
      evaluation. In this study, application of aroma extract dilution analysis using
      the volatile fraction before and after black tea (Darjeeling) samples were heat
      processed resulted in the detection of 10 odor-active peaks for which flavor
      dilution (FD) factors changed. Seven potent odorants were identified from these
      peaks by gas chromatography-mass spectrometry. Among these components, 3
      methylbutanal (stimulus), methional (potato-like), beta-damascenone (sweet),
      dimethyl trisulfide (putrid), and 2-methoxy-4-vinylphenol (clove-like) showed the
      highest FD factors after heat processing of the black tea sample. Therefore,
      these odorants were the most important components involved in changing the black
      tea odor during heat processing. In addition, the precursor of beta-damascenone
      in black tea infusion was investigated, and 3-hydroxy-7,8-didehydro-beta-ionol
      was determined to be one of the beta-damascenone-generating compounds for the
      first time.

PMID- 11453768
TI  - Changes in nitrogen compounds in must and wine during fermentation and biological
      aging by flor yeasts.
AB  - Urea, ammonium, and free amino acid contents were quantified in a must from Vitis
      vinifera cv. Pedro Ximenez grapes and in fermented wine and after a short aging
      of this wine by Saccharomyces cerevisiae race capensis yeast under variable
      oxygen availability conditions. The previous compounds were also determined in a
      wine in which the nitrogen source was depleted by the same race of flor yeast
      (old wine) and also following the addition of ammonium ion, L-glutamic acid, and
      L-proline. Under specific conditions such as low oxygen level and the absence of
      some nutrients, the yeasts release some amino acids including L-threonine, L
      tryptophan, L-cysteine, and L-methionine to the medium. These amino acids must
      originate primarily in a de novo synthesis from ethanol that regenerates NAD(P)+.
      On the basis of these results, the yeasts may be able to use amino acids not only
      as nitrogen sources but also as redox agents to balance the oxidation-reduction
      potential under conditions of restricted oxygen, when electron transport along
      the respiratory chain may be hindered or limited.

PMID- 11453769
TI  - Identification of benzethonium chloride in commercial grapefruit seed extracts.
AB  - Commercial grapefruit seed extracts (GSE) were extracted with chloroform. The
      solvent was evaporated, and the resulting solid was subsequently analyzed by high
      performance liquid chromatography, electrospray ionization mass spectrometry,
      nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis (by proton
      induced X-ray emission [PIXE] analysis). The main constituent was identified as
      benzethonium chloride, a synthetic antimicrobial agent commonly used in cosmetics
      and other topical applications. This compound comprised 8.03% (n = 2) of the
      liquid GSE sample. Higher amounts of benzethonium chloride were found in powder
      GSE samples.

PMID- 11453770
TI  - Free radical scavenging activities measured by electron spin resonance
      spectroscopy and B16 cell antiproliferative behaviors of seven plants.
AB  - In an effort to discover new antioxidant natural compounds, seven plants that
      grow in France (most of them in the Limousin countryside) were screened. Among
      these plants, was the extensively studied Vitis vinifera as reference. For each
      plant, sequential percolation was realized with five solvents of increasing
      polarities (hexane, chloroform, ethyl acetate, methanol, and water). Free radical
      scavenging activities were examined in different systems using electron spin
      resonance (ESR) spectroscopy. These assays were based on the stable free radical
      1,1-diphenyl-2-picrylhydrazyl (DPPH), the hydroxyl radicals generated by a Fenton
      reaction, and the superoxide radicals generated by the X/XO system.
      Antiproliferative behavior was studied on B16 melanoma cells. ESR results showed
      that three plants (Castanea sativa, Filipendula ulmaria, and Betula pendula)
      possessed, for the most polar fractions (presence of phenolic compounds), high
      antioxidant activities in comparison with the Vitis vinifera reference. Gentiana
      lutea was the only one that presented a hydroxyl scavenging activity for the
      ethyl acetate and chloroform fractions. The antiproliferative test results showed
      that the same three plants are the most effective, but for the apolar fractions
      (chloroform and hexane).

PMID- 11453771
TI  - Study of oat globulin conformation by Fourier transform infrared spectroscopy.
AB  - The conformation of oat globulin dispersions (10% in D2O) under the influence of
      pH, chaotropic salts, protein structure perturbants, and heating conditions was
      studied by Fourier transform infrared (FTIR) spectroscopy. The FTIR spectrum of
      oat globulin showed major bands from 1670 to 1634 cm(-1), corresponding to the
      four major types of secondary structures, that is, beta-turns, beta-sheets, alpha
      helices, and random coils. At extreme acidic and alkaline pH conditions, there
      were changes in intensity in the bands attributed to beta-sheet structures (1626,
      1634, and 1682 cm(-1)), and shifts of the bands to higher or lower wavenumbers,
      indicating changes in conformation. In the presence of some chaotropic salts, the
      1626 and 1634 cm(-1) bands were shifted upward, with a marked decrease in the
      intensity of the 1634 cm(-1) peak. The addition of several protein structure
      perturbants led to a slight shift in the alpha-helix/random coil bands and a
      marked reduction in the beta-sheet peaks, suggesting protein unfolding. Heating
      under aggregating conditions led to slight shifts in all of the major bands and
      progressive changes in the intensity of the alpha-helix, beta-sheet, and beta
      turn peaks, suggesting protein denaturation. This was accompanied by marked
      increases in intensity of the two intermolecular beta-sheet bands (1682 and 1624
      1626 cm(-1)) associated with the formation of aggregated strands. The IR spectra
      of soluble and insoluble aggregates showed a redistribution of native and
      extensively denatured proteins in the two fractions.

PMID- 11453772
TI  - Investigating the molecular heterogeneity of polysorbate emulsifiers by MALDI-TOF
      MS.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is a new technique that can be used to determine the molecular
      composition of polysorbate emulsifiers, which are commonly used as food
      additives. This is the first study to offer such a detailed examination of these
      heterogeneous compounds. MALDI-TOF MS is a powerful tool that can provide a
      polysorbate mass profile in less than two minutes. 2',4',6'
      Trihydroxyacetophenone monohydrate was chosen to be an ideal matrix, as it easily
      facilitated desorption and ionization, provided good resolution, and allowed for
      fast and simple preparation of the sample. By addition of aqueous 0.01 M
      potassium chloride, species were resolved exclusively as potassium adducts in the
      positive ion mode. MALDI-TOF MS analysis before and after saponification
      indicated the presence of unbound ethylene oxide polymers, as well as free and
      esterified sorbitan- and sorbide-based species. Some evidence for the presence of
      disorbitan-based species was provided. Also illustrated were the polydispersity
      of the oxyethylene chains, the degree of esterification, and the identity of
      esterified fatty acids.

PMID- 11453773
TI  - Antioxidant capacities and phenolics levels of French wines from different
      varieties and vintages.
AB  - Phenolics from grapes and wines can play a role against oxidation and development
      of atherosclerosis. Levels of phenolics, major catechins [(+)-catechin, (-)
      epicatechin, procyanidin dimers B1, B2, B3, and B4], phenolic acids (gallic acid
      and caffeic acid), caftaric acid, malvidin-3-glucoside, peonidin-3-glucoside, and
      cyanidin-3-glucoside were quantified by HPLC with UV detection for 54 French
      varietal commercial wines taken from southern France to study the antioxidant
      capacity and the daily dietary intake of these compounds for the French
      population. The highest antioxidant capacity was obtained with red wines and
      ranged from 12.8 mmol/L (Grenache) to 25.2 mmol/L (Pinot Noir). For white wines,
      Chardonnay enriched in phenolics by special wine-making was found to have an
      antioxidant capacity of 13.8 mmol/L, comparable to red wine values. For red wines
      classified by vintages (1996-1999) antioxidant capacities were approximately 20
      mmol/L and then decreased to 13.4 mmol/L for vintages 1995-1991. Sweet white
      wines have 1.7 times more antioxidant capacity (3.2 mmol/L) than dry white wines
      (1.91 mmol/L). On the basis of a still significant French wine consumption of 180
      mL/day/person, the current daily intake of catechins (monomers and dimers B1, B2,
      B3, and B4) averaged 5 (dry white wine), 4.36 (sweet white wines), 7.70 (rose
      wines), 31.98 (red wines), and 66.94 (dry white wine enriched in phenolic)
      mg/day/resident for the French population. Red wine, and particularly Pinot Noir,
      Egiodola, Syrah, Cabernet Sauvignon, and Merlot varieties, or Chardonnay enriched
      in phenolics during wine-making for white varieties contribute to a very
      significant catechin dietary intake.

PMID- 11453774
TI  - Generation of class-selective monoclonal antibodies against the penicillin group.
AB  - To develop a penicillin-specific ELISA, different attempts were made to obtain
      monoclonal antibodies specific for the common structure of penicillins.
      Ampicillin was coupled to different carrier proteins (bovine serum albumin,
      chicken ovalbumin, and thyroglobulin) to render it immunogenic. Different
      coupling methods were compared: two methods using a cross-linker (glutaraldehyde
      or a succinimide ester), one carbodiimide-mediated coupling method, and one
      method without any cross-linker or mediator molecule (physiological binding).
      Mice were immunized with the conjugates intraperitoneally or in the footpad. A
      screening ELISA was developed to detect anti-ampicillin antibodies in sera.
      Specificity and affinity of the antibodies were demonstrated by inhibiting their
      binding with a 10 mM solution of ampicillin. No difference could be observed
      using electrofusion or PEG-mediated fusion. For the production of the
      monoclonals, an intravenous final boost gave antibodies with better specificity
      and affinity than an intraperitoneal final booster injection. At least one anti
      ampicillin monoclonal antibody (19C9) cross-reacts with penicillin G, oxacillin,
      dicloxacillin, and carbenicillin, and not with sulfanilamide, chloramphenicol,
      neomycin, and streptomycin, and is therefore considered interesting for
      developing a penicillin-specific ELISA.

PMID- 11453775
TI  - Selection of hybrids and edible citrus species with a high content in the diosmin
      functional compound. Modulating effect of plant growth regulators on contents.
AB  - The purpose of this study is to identify species, hybrids, and cultivars of
      edible Citrus species with high contents of diosmin as a functional compound and
      also to identify the developmental progress of the fruit in which it reaches
      maximum levels; these findings would be useful for extraction purposes and for
      the modulating effect of plant growth regulators on diosmin content to increase
      the level of this flavone. The results obtained reveal that the highest contents
      of diosmin are present in immature fruits of certain varieties of citron (Buda's
      finger) and lemon (Meyer), whereas the contents in the edible parts of the fruits
      are irrelevant from a pharmacological point of view. Similarly, it is shown that
      it is possible to increase the content of this flavone using hormonal treatments
      (6-benzylaminopurine and 2,4-dichlorophenoxyacetic acid) during the early stages
      of fruit growth.

PMID- 11453776
TI  - Regioisomerism of triacylglycerols in lard, tallow, yolk, chicken skin, palm oil,
      palm olein, palm stearin, and a transesterified blend of palm stearin and coconut
      oil analyzed by tandem mass spectrometry.
AB  - Triacylglycerols (TAG) of lard, tallow, egg yolk, chicken skin, palm oil, palm
      olein, palm stearin, and a transesterified blend of palm stearin and coconut oil
      (82:18) were investigated by chemical ionization and collision-induced
      dissociation tandem mass spectrometry. Accurate molecular level information of
      the regioisomeric structures of individual TAGs was achieved. When existing in a
      TAG molecule of lard, palmitic acid occupied 90-100% of the sn-2 position. Within
      the major fatty acid combinations in tallow TAGs, the secondary position sn-2 was
      preferentially occupied in the decreasing order by oleoyl > palmitoyl > stearoyl
      residues, the order in saturated TAGs being myristoyl > stearoyl = palmitoyl.
      TAGs in egg yolk were more asymmetric than in chicken skin, with linoleic acid
      highly specifically attached in the yolk sn-2 carbon. Nearly 50% of yolk TAGs
      contained 52 carbon atoms with two or three double bonds. Linoleic, oleic, and
      palmitic acids were in the sn-2 location in decreasing quantities in palm oil and
      its fractions. Triacylglycerols of equal molecular weight behaved similarly in
      the fractionation process. Randomization of the parent oil TAGs was seen in the
      transesterified oil. The tandem mass spectrometric analysis applied provided
      detailed information of the distribution of fatty acids in individual
      combinations in TAGs.

PMID- 11453777
TI  - Comparison of quercetin and a non-orthohydroxy flavonol as antioxidants by
      competing in vitro oxidation reactions.
AB  - Two structurally related flavonols, quercetin and morin, along with
      protocatechuic acid (PA), beta-resorcylic acid (DHBA), and phloroglucinol
      carboxylic acid (PCA), which represent quercetin and morin degradation products,
      were assessed with respect to their antioxidant potency by chemical comparisons
      in competing oxidation reactions. The measurement of the antioxidant capacity was
      performed with the beta-carotene bleaching method, and the compounds were also
      tested with respect to their abilities to prevent lipid, protein, and DNA
      oxidation. The effect of concentration was also considered. The results obtained
      strongly suggested that quercetin is a powerful antioxidant in every system used,
      whereas morin is a much weaker antioxidant and in some cases may also have pro
      oxidant action. PA and PCA were always inferior antioxidants compared to the
      parent molecule quercetin; DHBA and PCA exhibited activities comparable to that
      of morin in reaction comparisons.

PMID- 11453778
TI  - Influence of aeration on the physiological activity of flor yeasts.
AB  - The effect of periodic aeration on the physiological activity of a strain of
      Saccharomyces cerevisiae yeast during development of velum (flor) and biological
      aging of Sherry wine of the Fino type was investigated. L-Proline amino acid was
      the main nitrogen source for yeasts cells during the biological aging, and its
      exhaustion may be the cause of the production and consumption of other compounds
      that are involved in the aroma of wines. Aeration was found to increase adenylate
      energy charge, growth, and viability of the yeast cells. Also, it affected the
      intracellular redox equilibrium and the consumption and production of compounds
      including acetoin, acetaldehyde, higher alcohols, ethanol, glycerol, and acetic
      acid. Acetaldehyde reached its highest level after the second aeration, which
      coincided with the exhaustion of the nitrogen source in the medium. The enzyme
      activity of alcohol dehydrogenases I and II decreased immediately after each
      aeration, subsequently increasing once all of the dissolved oxygen in the wine
      had been consumed by yeast cells. Aldehyde dehydrogenase activity was detected
      only after the first aeration, and it may be related to the production and
      consumption of acetic acid in the wine.

PMID- 11453779
TI  - Effect of partial replacement of gum arabic with carbohydrates on its
      microencapsulation properties.
AB  - Gum arabic solutions (10% w/v) were emulsified with soy oil at oil/gum ratios of
      0.25-5.0. At oil/gum ratios <1.0, it was established that gum arabic could be
      partially replaced with a nonsurfactant carbohydrate. To assess different
      carbohydrates as replacers for gum arabic, emulsions and spray-dried emulsions of
      soy oil and mixed solutions (10% w/v) of gum arabic and a range of carbohydrate
      wall materials (oil/gum = 0.5) were prepared and analyzed. Maize starch and
      glucose were ineffective as partial replacers of gum arabic, but maltodextrins of
      various dextrose equivalence values (5.5-38) successfully replaced 50% of the gum
      arabic. The microencapsulation efficiency of the gum arabic/maltodextrin
      stabilized powders was further increased by increasing total solids of the feed
      to the dryer and by increasing the atomizer nozzle diameter.

PMID- 11453780
TI  - Purification and substrate specificity of transglutaminases from blood and
      Streptoverticillium mobaraense.
AB  - A procedure for a fast and simple purification of bovine plasma transglutaminase
      was developed, which resulted in a homogeneous enzyme preparation. Two different
      procedures were developed for the purification of pig erythrocyte
      transglutaminase, both of which resulted in partial purification. Both enzymes
      were used in cross-linking reactions of alpha-lactalbumin, beta-lactoglobulin,
      bovine serum albumin, casein, hemoglobin, glycinin, and myosin. The substrate
      specificity was compared to that of bacterial transglutaminase isolated from
      Streptoverticillium mobaraense. The bacterial transglutaminase caused cross
      linking of a wider range of proteins and, thus, exhibited a lower substrate
      specificity than the blood transglutaminases. In addition, differences exist in
      the necessity of the addition of reducing agents. These differences allow
      specific applications of blood and bacterial transglutaminases at protein cross
      linking in single or complex protein systems.

PMID- 11453781
TI  - Mechanism of pressure-induced gelation of milk.
AB  - The pressure-induced gelation of concentrated skimmed milk and milk-sugar
      mixtures was studied to discover the main components responsible for gelation.
      The major protein component responsible for gelation is micellar casein. Gelation
      occurs at similar pressures to casein micelle disintegration in dilute milk, and
      both can be prevented by inclusion of excess calcium chloride. Transmission
      electron micrographs show that the protein network is formed from particles with
      diameters approximately an order of magnitude smaller than those of intact casein
      micelles. Gelation occurs on decompression and is found to be baroreversible.
      Concentrations of sugar up to 30% reduce the critical concentration of casein
      required for gelation, but higher sugar concentrations inhibit gelation. A
      mechanism of gelation based on the aggregation of casein submicelles formed by
      pressure-induced disintegration of casein micelles is proposed. Observations on
      the effect of sucrose on gelation are discussed in terms of the influence of
      sugars on the solvent quality in aqueous casein systems.

PMID- 11453782
TI  - Effect of Maillard reaction with glucose and ribose on solubility at low ionic
      strength and filament-forming ability of fish myosin.
AB  - It was previously reported that water-soluble fish meat can be prepared by the
      Maillard reaction with reducing monosaccharides. To clarify the molecular
      mechanism of the solubility improvement caused by the glycosylation, carp myosin
      and myosin rod region were reacted with glucose and ribose, and their
      solubilities and filament-forming abilities at low ionic strength were
      investigated. The solubility of myosin in 0.1 M NaCl increased with the
      glycosylation and reached the same level as in 0.5 M NaCl. Although the same
      solubility improvement was observed in glycosylated myosin rod and the alpha
      helix content remained unchanged, the filament-forming ability was completely
      lost by the glycosylation. These results suggest that the solubility improvement
      of fish meat at low ionic strength is caused by the solubilization of myosin and
      the dissociation of myosin filaments.

PMID- 11453783
TI  - Effects of dietary supplementation with Yucca schidigera Roezl ex Ortgies and its
      saponin and non-saponin fractions on rat metabolism.
AB  - Yucca schidigera Roezl ex Ortgies, family Lillaceae, was fractionated with butan
      1-ol to yield a butanol extractable fraction (BE; saponin fraction) and a non
      butanol fraction (NBE; non-saponin fraction). Four groups of eight male rats were
      allowed ad libitum access to diets supplemented with water (control) or 200 mg x
      kg(-1) total Y. schidigera (TOT) or 200 mg x kg(-1) of each of the fractions (NBE
      or BE). The effects of dietary supplementation with the fractions and their
      interactions in TOT were analyzed according to the factorial experimental design
      by two-way analysis of variance. All three supplementation groups displayed
      significantly reduced serum urea levels (P < 0.05). The TOT and NBE fractions
      were found to significantly increase serum insulin levels (P < 0.01) in the
      absence of any fluctuations in serum glucose levels. Urea cycle enzyme
      activities, namely, arginase (EC 3.5.3.1) and argininosuccinate lyase (EC
      4.3.2.1), were significantly decreased (P < 0.05) in vivo, although no effect was
      observed in vitro. Both fractions displayed effects, indicating that the active
      constituents are present in both fractions.

PMID- 11453784
TI  - Physicochemical studies of caroubin: a gluten-like protein.
AB  - It has been reported that caroubin, a protein mixture obtained from carob seeds,
      has rheological properties similar to those of gluten. Comparative studies of the
      effects of hydration and temperature on caroubin and gluten were carried out with
      the aid of NMR, FTIR, scanning electron microscopy, and differential scanning
      calorimetry techniques. The results show that caroubin has a more ordered
      structure than gluten and that hydration has little effect on its secondary
      structure when compared to gluten. Caroubin is more easily accessible to water
      than gluten, suggesting that caroubin is more hydrophilic in nature. On
      hydration, caroubin, like gluten, forms fibrillar structures and sheets.

PMID- 11453785
TI  - Antioxidant activity of extracts from Acacia confusa bark and heartwood.
AB  - The antioxidant activity of extracts from bark and heartwood of Acacia confusa
      was evaluated by various antioxidant assays, including free radical and
      superoxide radical scavenging assays and lipid peroxidation assay as well as
      hydroxyl radical-induced DNA strand scission assay. In addition, an ex vivo
      antioxidant assay using a flow cytometric technique was also employed in this
      study. The results indicate that both bark and heartwood extracts clearly have
      strong antioxidant effects. Similar inhibitory activities for each test sample
      were found for both 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical generation and
      lipid peroxidation. As for the superoxide radical scavenging activity, the
      heartwood extract was more effective than the bark extract. Furthermore, the
      heartwood extract protected PhiX174 supercoiled DNA against strand scission
      induced by ultraviolet photolysis of H2O2, and it reduced the amounts of
      intracellular hydrogen peroxide, a reactive oxygen species, when it was co
      incubated with human promyelocytic leukemia (HL-60) cells under oxidative stress.

PMID- 11453786
TI  - Application of ICP sector field MS and principal component analysis for studying
      interdependences among 23 trace elements in Polish beers.
AB  - Twenty-three metallic elements, including almost all essential and toxic metals
      such as lead, cadmium, mercury, arsenic, silver, and thallium, have been
      quantified in 35 types of bottled and canned Polish beer by using double-focusing
      sector field inductively coupled plasma mass spectrometry (ICP-MS) with
      ultrasonic nebulization. The samples were digested using concentrated HNO3 in
      closed PTFE vessels and applying microwave energy under pressure. The means and
      medians of the concentrations of Rb, Mn, and Fe were on the order of 200 ng/mL;
      Cu, Zn, V, Cr, Sn, As, Pb, and Ni were detected at 1-5 ng/mL; Ag, Ga, Cd, Co, Cs,
      Hg, U, and Sb were found at < 1 ng/mL; and In, Tl, Bi, and Th were present at <
      0.1 ng/mL. The concentrations of Hg, Cd, As, Pb, and Zn were 1-3 orders of
      magnitude lower than proposed tolerance limits. The interdependences among
      determined trace elements were examined using the principal component analysis
      (PCA) method. The PCA model explained 74% of the total variance. The metals tend
      to cluster together (As, Tl, Cs, Sn, Th, Bi, and Hg; Cd and Co; Cs and Cr; Fe and
      Zn; Mn and V).

PMID- 11453787
TI  - Properties of diphenolase from Vanilla planifolia (Andr.) shoot primordia
      cultured in vitro.
AB  - Properties of diphenolase (PPO, EC1.10.3.1) from vanilla (Vanilla planifolia
      Andr.) shoot primordia culture were investigated. Two pH optima of the enzyme
      extraction at pH 6 and 8 were found. Nevertheless, the enzymes shared the same
      optimum pH of activity-between pH 3 and 4. Sodium dodecyl sulfate slightly
      improved diphenolase extraction but caused a 3-fold increase in its specific
      activity. The extracts of pH 6 and 8.0 revealed three isozyme bands after
      polyacrylamide gel electrophoresis-two of them were similar in both extracts and
      two distinct. The enzyme showed high thermal stability-no loss was observed after
      120 min at 50 degrees C. Diethyldithiocarbamic acid, ethylenediaminetetracetic
      acid disodium salt, ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'
      tetraacetic acid, L-ascorbic acid, dithiothreitol, glutathione (reduced), and
      beta-mercaptoethanol were found to be potent inhibitors of the diphenolase
      studied. The enzyme showed also monophenolase activity. Km and Vmax were
      calculated with monophenols [p-coumaric acid, 3-(p-hydroxyphenyl)propionic acid,
      4-hydroxybenzyl alcohol, 4-hydroxybenzaldehyde, 4-hydroxybenzoic acid] and with
      diphenols (caffeic acid, hydrocaffeic acid, chlorogenic acid, 4-methylcatechol,
      protocatechuic aldehyde and acid, and 3,4-dihydroxyphenylalanine). The highest
      Vmax was found with 4-hydroxybenzyl alcohol and the greatest affinity to
      protocatechuic acid, respectively-the most abundant monophenol and one of the
      least abundant o-diphenols in the studied Vanilla tissue.

PMID- 11453788
TI  - Comparison of the antioxidant activity of commonly consumed polyphenolic
      beverages (coffee, cocoa, and tea) prepared per cup serving.
AB  - In this study, the in vitro low-density lipoprotein oxidation model was used to
      assess the relative antioxidant activity of the polyphenolic beverages tea,
      coffee, and cocoa on a cup-serving basis. The beverages were prepared as 0.7-2.5%
      soluble coffee and 1.5-3.5% cocoa; teas (green, black, or herbal) were prepared
      as one tea bag infused over 5 min in 220 mL of hot water. Under these standard
      cup serving conditions, the antioxidant activity as determined by the lag time
      was in the range of 292-948 min for coffee, 217-444 min for cocoa, 186-338 min
      for green tea, 67-277 min for black tea, and 6-78 min for herbal tea. Addition of
      milk did not alter the antioxidant activity. The influence of coffee bean source
      and degree of roasting was further investigated. Green coffee beans of Robusta
      coffee exhibited a 2-fold higher antioxidant activity than Arabica coffee, but
      after roasting this difference was no longer significant. In conclusion, these
      commonly consumed beverages have a significant antioxidant activity, the highest
      being soluble coffee on a cup-serving basis.

PMID- 11453789
TI  - Rapid gastric fluid digestion and biochemical characterization of engineered
      proteins enriched in essential amino acids.
AB  - The barley high lysine (BHL) proteins are nutritionally enhanced derivatives of
      barley chymotrypsin inhibitor-2 (CI-2). A compactly folded new CI-2 derivative,
      BHL9, was engineered with the highest content of threonine, tryptophan, and
      isoleucine yet achieved in this protein family (15.1, 9.4, and 12.1 wt %,
      respectively). BHL9 had an unfolding midpoint of 5.5 M guanidinium chloride,
      significantly greater than values for wild type (3.9 M) or for the previously
      most stable BHL protein, BHL8 (3.6 M). BHL9 and all other derivatives were
      digested within 15 s in simulated gastric fluid (SGF), suggesting nutritional
      availability upon ingestion. Denaturation of the proteins in SGF minus pepsin was
      revealed by changes in their fluorescence emission spectra and/or far UV circular
      dichroism spectra. The proteins lack homology to known allergens. Significantly,
      the BHL8 and BHL9 proteins were stable to proteases at pH 7.5 or 8.0, attesting
      to their potential for high expression in plants.

PMID- 11453790
TI  - Free radical scavenging properties of conjugated linoleic acids.
AB  - Conjugated linoleic acids (CLA) were investigated for free radical scavenging
      properties against the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH.) by
      electron spin resonance (ESR) spectrometry and spectrophotometric methods. ESR
      results demonstrated that CLA directly reacted and quenched free DPPH radicals in
      benzene, while spectrophotometric analysis showed the radical scavenging capacity
      of CLA in ethanol. Dose and time effects of CLA-DPPH. reactions were observed in
      both tests. The ED(50) of CLA was 18 mg/mL under experimental conditions. CLA are
      much weaker radical scavengers as compared to vitamin E, vitamin C, and BHT.
      Kinetics of CLA-DPPH. reactions was different to that of linoleic acid (LA)-DPPH.
      reactions. CLA reacted and quenched DPPH radicals at all tested levels without a
      lag phase, while LA had a lag phase and showed no radical quenching activity at
      levels of 5-80 mg/mL in 30 min. These data indicated that CLA can provide
      immediate protection against free radicals, but LA cannot.

PMID- 11453791
TI  - Electron spin resonance studies of free radicals in gamma-irradiated soybean
      paste.
AB  - Free radicals in gamma-irradiated soybean paste were investigated by electron
      spin resonance (ESR) spectroscopy to determine the effect of temperature (77-296
      K) and moisture content (1-54%) of samples irradiated at high dose (1-40 kGy).
      The samples were kept in liquid nitrogen (77 K) during irradiation and subsequent
      ESR measurements. The spectra shown at 77 K consisted of the hydrogen atom lines
      at low and high field and complicated symmetric spectrum. By increasing the
      microwave power, the line shape of ESR spectra altered, which indicated the
      detection of different paramagnetic centers at different microwave powers. In
      saturation curves, it was possible to select four types of spectra components
      which were different in their relaxation times. By the different irradiation
      doses, the change in free radical concentration showed a curvilinearly increasing
      relationship with irradiation dose in wet samples, whereas a proportional
      relationship was observed with dried samples. This might indicate that the
      indirect process of free radical formation was involved with the existence of
      free water radicals in the wet samples.

PMID- 11453792
TI  - Solid-phase extraction followed by liquid chromatography-mass spectrometry for
      trace determination of beta-lactam antibiotics in bovine milk.
AB  - A confirmatory assay able to unambiguously identify and quantify 10 approved-for
      use beta-lactam antibiotics in milk below stipulated U.S. and EU tolerance levels
      is presented. beta-Lactams are extracted from 10 mL of intact milk by a
      Carbograph 4 cartridge. After solvent removal, residue reconstitution, and
      filtration, a completely transparent and uncolored extract is injected into a
      liquid chromatography -mass spectrometry (LC-MS) instrument equipped with an
      electrospray (ES) ion source and a single quadrupole. During the chromatographic
      run, the ES/MS system is operated first in the positive-ion mode (PI) and then in
      the negative-ion (NI) mode. This is done to circumvent matrix interferences
      resulting in remarkable signal weakening of the last-eluted analytes, when
      detecting them as [M+H]+ adduct ions. MS data acquisition is performed by a time
      scheduled three-ion selected ion monitoring program. At the 5 ng/mL level,
      recoveries of the beta-lactams are between 70 (nafcillin) and 108% (cephalin),
      with relative standard deviations ranging between 5 (oxacillin) and 11%
      (amoxicillin and ceftiofur). The response of the ES/MS detector is linearly
      related to injected amounts up to 500 ng, irrespective of the chemical
      characteristics of the beta-lactams and the acquisition mode selected (PI or NI
      modes). Limits of quantification, based on a minimal value of the signal-to-noise
      ratio of 10, were estimated to be within 0.4 (cephalin) and 3 ng/mL
      (dicloxacillin). Analyses of milk samples taken after intramammary application of
      amoxicillin showed that 1.2 ng/mL of this penicillin was still present 6 days
      after treatment. At this concentration level, the identification power of the
      method is not weakened, as signals of the three product ions of amoxicillin are
      still well distinguishable from the background noise.

PMID- 11453793
TI  - Regioselective dimerization of ferulic acid in a micellar solution.
AB  - Dehydrodimers of hydroxycinnamates play an important role in the cross-linking of
      plant cell walls. An aqueous solution of quaternary ammonium salts with a long
      aliphatic chain is known to spontaneously organize itself into micelles with the
      ionic part at the outer sphere. It is shown that regioisomeric ferulic acid
      dehydrodimers can be obtained in one step from trans-ferulic acid after
      attachment to these micelles and using the biomimetic peroxidase-H2O2 system. The
      surfactant hexadecyltrimethylammonium hydroxide yielded trans-4-(4-hydroxy-3
      methoxybenzylidene)-2-(4-hydroxy-3-methoxyphenyl)-5-oxotetrahydrofuran-3
      carboxylic acid (25%), (E,E)-4,4'-dihydroxy-5,5'-dimethoxy-3,3'-bicinnamic acid
      (21%), and trans-5-[(E)-2-carboxyvinyl]-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy
      2,3-dihydrobenzofuran-3-carboxylic acid (14%), whereas the surfactant
      tetradecyltrimethylammonium bromide gave 4-cis, 8-cis-bis(4-hydroxy-3
      methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane-2,6-dione (18%) as the main product.
      The use of micelles appears to be not only a new way to synthesize regioisomeric
      ferulic acid dehydrodimers but may also help to understand the regiospecificity
      of dimeric hydroxycinnamate formation in vivo.

PMID- 11453794
TI  - Antioxidant activity of Centaurium erythraea infusion evidenced by its superoxide
      radical scavenging and xanthine oxidase inhibitory activity.
AB  - Centaurium erythraea Rafin. (Gentianaceae) has long been used in traditional
      medicine. This plant contains considerable amounts of polyphenolic compounds,
      namely, xanthones and phenolic acids as the main constituents. Because phenolic
      groups exhibit activity as radical scavengers and/or metal chelators, this study
      evaluated the superoxide radical scavenging properties of a lyophilized infusion
      obtained from C. erythraea flowering tops. Superoxide radical scavenging activity
      was assayed using enzymatic (xanthine/xanthine oxidase) and nonenzymatic
      (NADH/phenazine methosulfate) superoxide generating systems. This study provided
      evidence that C. erythraea exhibits interesting antioxidant properties, expressed
      either by the capacity to scavenge superoxide radical or to noncompetitively
      inhibit xanthine oxidase. The main phenolic compounds present in this extract
      were several esters of hydroxycinnamic acids, namely, p-coumaric, ferulic, and
      sinapic acids.

PMID- 11453795
TI  - Calcium, iron, and zinc uptake from digests of infant formulas by Caco-2 cells.
AB  - Our aim was to estimate the bioavailability of calcium, iron, and zinc from
      infant formulas using a model that includes in vitro digestion and a Caco-2 cell
      culture to estimate the uptake. The cell culture conditions were selected, and
      uptake assays were carried out first with calcium, iron, and zinc standard
      solutions, and then with the soluble fraction of enzymatic digests of an adapted
      milk-based and a soy-based infant formula. It was not possible to measure the
      uptake of calcium, iron, and zinc from standard solutions added to the cell
      cultures in amounts similar to those present in infant formula digests with our
      method. The fact that it was, however, possible in the case of enzymatic digests
      suggests the presence of components in the digests that enhance mineral uptake.
      When mineral uptakes were expressed as percentages of the mineral present,
      statistically significant differences were found in the case of calcium between
      the uptake from the milk- and the soy-based formulas. For iron and zinc no such
      differences were observed.

PMID- 11453796
TI  - Characterization of a vitamin B12 compound from unicellular coccolithophorid alga
      (Pleurochrysis carterae).
AB  - A unicellular coccolithophorid alga, Pleurochrysis carterae, contained 125.4 +/-
      1.2 microg of vitamin B12 per 100 g dry cell weight of the lyophilized algal
      cells. A vitamin B12 compound was purified from the lyophilized algal cells and
      partially characterized. The silica gel 60 TLC and reversed-phase HPLC patterns
      of the purified pink-colored compound were identical to those of authentic
      vitamin B12, but not those of vitamin B12 analogues inactive for humans. When 22
      week-old B12-deficient rats which excreted substantial amounts of methylmalonic
      acid (75.5 +/- 12.3 mg/day) in urine were fed the P. carterae (10 g per kg diet)
      supplemented diet for 12 d, urinary methylmalonic acid excretion (as an index of
      vitamin B12 deficiency) of the rats became undetectable and hepatic vitamin B12
      level of the rats was significantly increased.

PMID- 11453797
TI  - Stage of harvest and polyunsaturated essential fatty acid concentrations in
      purslane (Portulaca oleraceae) leaves.
AB  - Purslane is a nutritious vegetable crop rich in the polyunsaturated essential
      fatty acids (PUEFA) alpha-linolenic acid (LNA) and linoleic acid (LA), which are
      essential for normal human growth, health promotion, and disease prevention.
      Total lipids and fatty acid concentrations at three stages of harvest (6-, 10-,
      and 14-true-leaf stages) were examined in a cultivated variety of purslane
      (Portulaca oleraceae L. var. sativa). The 14-true-leaf stage of growth was found
      to be ideal for harvest because at this stage the leaf area, shoot fresh weight,
      shoot dry weight, and PUEFA concentrations per gram of leaf fresh weight were
      higher (P < or = 0.05) than at the 6- and 10-true-leaf stages of growth. The LNA
      to LA ratio was also highest at the 14-true-leaf stage.

PMID- 11453798
TI  - Methyl jasmonate stimulates aflatoxin B1 biosynthesis by Aspergillus parasiticus.
AB  - Aflatoxin B1 (AFB1) is a highly toxic and carcinogenic metabolite produced by
      certain Aspergillus species on agricultural commodities. One factor promoting the
      production of aflatoxin is the presence of high levels of fatty acid
      hydroperoxides often found in plant material under stress. Jasmonic acid (JA) and
      its methyl ester (MeJA) are derived from linolenic acid, and their biosyntheses
      involve the production of lipid hydroperoxides. Exposure of aflatoxigenic mold to
      jasmonates is likely because the mold attacks plant material and possibly
      initiates the production of jasmonates. In this study the effect of MeJA on the
      growth of Aspergillus parasiticus and AFB1 biosynthesis is reported. MeJA, at a
      final concentration of 10(-4) M in yeast extract sucrose medium, did not have any
      apparent effect on mycelial growth during the 16 days of observation but did
      increase significantly the levels of AFB1 after the seventh day of growth. After
      the ninth day, AFB1 production was decreased in contrast to the control cultures,
      where the production was constantly increasing. AFB1 determination was performed
      by immunoaffinity and HPLC after derivatization to AFB2a.

PMID- 11453799
TI  - Guar gum reduces trichloroethylene accumulation in the body by reducing TCE
      absorption and fat tissue mass.
AB  - Two studies were conducted regarding the effects of guar gum on accumulation and
      metabolism of trichloroethylene (TCE). In study 1, 6- and 14-weeks-old rats were
      given a single oral dose of 100 mg of trichloroethylene (TCE). Ten hours after
      administration of TCE, a marked positive correlation was noted between relative
      fat tissue weights and TCE distribution in fat tissues. Therefore, a small mass
      of fat tissue apparently limited TCE accumulation. In study 2, each of four
      groups of rats was fed one of four diets: cellulose-soybean oil, cellulose
      docosahexaenoic acid (DHA), guar gum-soybean oil, or guar gum-DHA for 3 weeks and
      then all were given TCE as in study 1. The rate of decrease of TCE distributed in
      fat tissues of groups fed guar gum compared with corresponding groups fed
      cellulose was greater than the rate of decrease in relative weight of these
      tissues. TCE absorption by groups fed guar gum decreased 12% compared with TCE
      absorption of corresponding groups fed cellulose. Therefore, guar gum decreased
      TCE accumulation in the body by reducing TCE absorption and fat tissue mass.

PMID- 11453802
TI  - Eradication of angiolymphoid hyperplasia with eosinophilia by copper vapor laser.

PMID- 11453803
TI  - On first looking into Pernkopf's atlas (part 2).

PMID- 11453805
TI  - Mycophenolate mofetil is effective in the treatment of atopic dermatitis.
AB  - OBJECTIVE: To evaluate whether mycophenolate mofetil, a new immunosuppressive
      agent, is effective for treating moderate-severe atopic dermatitis (AD). DESIGN:
      In an open-label pilot study, mycophenolate mofetil, 1 g, was given orally twice
      daily for 4 weeks. At week 5, the dosage was reduced to 500 mg twice daily until
      study end (week 8). Patients were followed up for 20 weeks. SETTING: University
      hospital dermatology department. PATIENTS: Ten consecutive patients with moderate
      severe AD nonresponsive to standard therapy. MAIN OUTCOME MEASURE: Severity of AD
      as measured using the subjective SCORAD [SCORing Atopic Dermatitis] index.
      RESULTS: Clinical efficacy was measured every 2 weeks using the subjective SCORAD
      index. Treatment with mycophenolate notably reduced the severity of AD within 4
      weeks in all patients (P<.05), and after 8 weeks the mean +/- SD SCORAD index
      dropped from the pretreatment value of 49.2 +/- 13.8 to 21.9 +/- 26.5 (P<.01).
      One patient had to discontinue mycophenolate therapy after 4 weeks because of the
      development of herpes retinitis. Except for this event, mycophenolate was
      tolerated well in all patients. Six of 7 patients who had responded to
      mycophenolate monotherapy had no relapse of disease during 20-week follow-up. In
      the 7 patients who finished the study, the SCORAD index was reduced by 74%, from
      44.0 +/- 7.8 before treatment to 11.4 +/- 5.9 at 20-week follow-up. CONCLUSIONS:
      Mycophenolate is a highly effective drug for treating moderate-severe AD, with no
      serious adverse effects occurring in any patients. Thus, mycophenolate might
      develop into a promising alternative in the therapy of moderate-severe AD.

PMID- 11453806
TI  - Primary generalized and localized hypertrichosis in children.
AB  - OBJECTIVE: To review the causes, presentation, and therapy of primary generalized
      and localized symmetrical hypertrichosis in children. DESIGN: Retrospective
      medical record review. SETTING: Academic specialty referral clinic for pediatric
      dermatological disorders. PATIENTS: Case series of 11 prepubertal male and female
      patients who had idiopathic hypertrichosis between July 1, 1990, and November 30,
      1999. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical distribution of
      increased hair growth and types of hair removal methods used. RESULTS: Seven
      girls and 4 boys, ranging in age from 4 months to 11 years, were evaluated. Four
      patients showed generalized hypertrichosis. The other 7 patients had localized
      symmetrical hypertrichosis, representing the subsets of hypertrichosis cubiti,
      anterior cervical hypertrichosis, posterior cervical hypertrichosis, and faun
      tail deformity. All patients with generalized hypertrichosis manifested the
      condition at birth; the age of onset in children with localized symmetrical
      primary hypertrichosis ranged from birth to 4 years. One girl with generalized
      hypertrichosis had gingival hyperplasia and the girl with faun tail deformity had
      bony diastematomyelia with spina bifida occulta. The medical histories and
      physical examination findings of all of the children were otherwise unremarkable.
      All patients were referred for diagnostic and therapeutic considerations.
      CONCLUSIONS: Primary hypertrichotic conditions, whether localized or generalized,
      are rare in pediatric patients and of unknown origin. Although otherwise benign,
      these disorders may result in cosmetic disfigurement and psychosocial trauma for
      patients and families. Patients and their families should be adequately advised
      of the available treatment methods for both temporary and permanent hair removal.

PMID- 11453807
TI  - Long-pulsed Nd:YAG laser-assisted hair removal in pigmented skin: a clinical and
      histological evaluation.
AB  - OBJECTIVE: To determine the safety and effectiveness of a long-pulsed Nd:YAG
      laser at 1064 nm in effecting long-term hair reduction in patients with darkly
      pigmented skin. DESIGN: Nonrandomized before-after clinical and histological
      trial. SETTING: Private practice, ambulatory care facility. PATIENTS: Twenty
      women with skin phototypes IV through VI and dark brown to black terminal hair on
      the face, axillae, or legs. INTERVENTION: A series of 3 long-pulsed (50
      millisecond) 1064-nm Nd:YAG laser treatments at fluences ranging from 40 to 50
      J/cm(2) were delivered to the identified treatment areas on a monthly basis by a
      single operator. MAIN OUTCOME MEASURES: Global clinical grading scores of
      comparable before-after treatment photographs were determined by 2 independent
      medical assessors during each laser session and 1, 3, 6, and 12 months
      postoperatively. A dermatopathologist reviewed unmarked histological specimens
      obtained at baseline, immediately after the initial laser treatment, and at 1 and
      6 months after the final laser session. RESULTS: Substantial hair reduction was
      seen after each of the 3 treatment sessions. Prolonged hair loss was observed 12
      months after the final laser treatment (70%-90% hair reduction). Axillary hair
      was substantially more responsive to laser irradiation than was hair located on
      the legs and face. Adverse effects included mild to moderate treatment pain and
      rare occurrences of vesiculation and transient pigmentary alteration without
      fibrosis or scarring. Histological tissue changes mirrored clinical response
      rates, with evidence of selective follicular injury without epidermal disruption.
      CONCLUSION: The long-pulsed 1064-nm Nd:YAG laser is a safe and effective method
      of long-term hair reduction in patients with darkly pigmented skin.

PMID- 11453808
TI  - Clinical, histological, and immunophenotypic characteristics of injection site
      reactions associated with etanercept: a recombinant tumor necrosis factor alpha
      receptor: Fc fusion protein.
AB  - OBJECTIVE: To study injection site reactions (ISRs) associated with etanercept
      therapy. DESIGN: Retrospective chart review, along with prospective analysis of
      selected patients experiencing ISRs associated with etanercept therapy. SETTING:
      Academic rheumatology/immunology unit and dermatology clinic. SUBJECTS: Patients
      with rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory
      seronegative arthritis, psoriatic arthritis, psoriasis, or inflammatory bowel
      disease. INTERVENTIONS: Skin biopsy specimens were taken from selected patients
      experiencing ISRs. MAIN OUTCOME MEASURES: Incidence of IRSs and histological and
      immunophenotypic analysis of ISRs in 3 patients undergoing prospective study.
      RESULTS: Twenty-one (20%) of 103 of all patients receiving etanercept reported
      ISRs, all within the first 2 months of inception of therapy. The reactions
      occurred 1 to 2 days after the last injection and resolved within a few days.
      Moreover, eventual waning of reactions was observed, with none proving to be dose
      limiting. Histological examination of all biopsy specimens showed an inflammatory
      infiltrate composed of predominantly lymphoid cells and some eosinophils, in a
      perivascular cuffing pattern, without evidence of leukocytoclastic vasculitis.
      The infiltrating lymphoid cells were predominantly activated mature (HLA
      DR(+)/CD3(+)/CD4(-)/CD8(+)) cytotoxic T lymphocytes, with a small number of
      CD4(+) cells. A biopsy specimen from a recall ISR showed strong HLA-DR expression
      by epidermal keratinocytes. CONCLUSIONS: Injection site reactions associated with
      etanercept therapy are common, and may be an example of a T-lymphocyte-mediated
      delayed-type hypersensitivity reaction, with waning over time due to eventual
      induction of tolerance.

PMID- 11453809
TI  - Absence of T(H)2 cytokine messenger RNA expression in CD30-negative primary
      cutaneous large T-cell lymphomas.
AB  - BACKGROUND: Previous studies demonstrating that the neoplastic cells in Sezary
      syndrome and tumor stage mycosis fungoides express interleukin 4 (IL-4), IL-5,
      and IL-10 have resulted in the concept that cutaneous T-cell lymphomas are
      derived from CD4(+) T cells with a T(H)2 type cytokine profile. OBJECTIVE: To
      determine the cytokine profile in CD30(-) primary cutaneous large T-cell
      lymphomas, which represent a subgroup of cutaneous T-cell lymphoma with an
      aggressive clinical behavior (5-year survival rate of 15%). DESIGN AND METHODS:
      Seven biopsy specimens were taken from 4 patients with CD30(-) primary cutaneous
      large T-cell lymphomas and studied for the expression of T(H)1 (IL-2 and
      interferon gamma) and T(H)2 (IL-4, IL-5, IL-10) cytokines using a reverse
      transcription-polymerase chain reaction technique. Skin biopsy specimens from
      patients with Sezary syndrome, mycosis fungoides, atopic dermatitis, or psoriasis
      were included as controls. RESULTS: In the 7 CD30(-) primary cutaneous large T
      cell lymphomas showing an almost pure population of large tumor cells (>90%), no
      expression of IL-4 was found, and IL-5 was only found in 1 of 7 cases. In control
      biopsy specimens, expression of IL-4 and/or IL-5 was demonstrated in atopic
      dermatitis (3/3), tumor stage mycosis fungoides (2/2), and Sezary syndrome (3/3),
      but not in plaque stage mycosis fungoides. CONCLUSION: Our results demonstrate
      that CD30(-) primary cutaneous large T-cell lymphomas do not produce T(H)2
      cytokines, illustrating that not all cutaneous T-cell lymphomas have a T(H)2
      cytokine profile.

PMID- 11453810
TI  - Malignant peripheral nerve sheath tumors associated with neurofibromatosis type
      1: a clinicopathologic and molecular study of 17 patients.
AB  - OBJECTIVE: To identify potential prognostic factors and criteria for early
      detection of malignant peripheral nerve sheath tumors associated with
      neurofibromatosis type 1 (NF1). DESIGN: Retrospective study of malignant
      peripheral nerve sheath tumors in a cohort of 395 patients with NF1 followed up
      between October 1, 1988, and January 1, 1999; review of the clinical and
      histological characteristics of treatment and course; and analysis of p53
      mutations and overexpression in tumors. SETTING: Teaching hospital referral
      neurofibromatosis center for adults. PATIENTS: Seventeen patients with NF1 (9
      males and 8 females). Mean +/- SD patient age at diagnosis was 32 +/- 14 years.
      MAIN OUTCOME MEASURES: (1) Clinical symptoms, (2) comparison of p53 mutations and
      overexpression in benign vs malignant tumors; and (3) median survival. RESULTS:
      Twelve patients had high-grade tumors. All tumors except 1 developed on
      preexisting nodular or plexiform neurofibromas. Pain and enlarging mass were the
      first and predominant signs. None of the benign tumors displayed significant p53
      staining or p53 mutations. Six of 12 malignant tumors significantly overexpressed
      p53, and 4 of 6 harbored p53 missense mutations. Median survival was 18 months
      overall, 53 months in peripheral locations, and 21 months in axial locations.
      CONCLUSIONS: Malignant peripheral nerve sheath tumors are highly aggressive in
      NF1. They mostly arise from plexiform or nodular neurofibromas. Investigations
      and deep biopsy of painful and enlarging nodular or plexiform neurofibromas
      should be considered in patients with NF1. Late appearance of p53 mutations and
      overexpression precludes their use as predictive markers of malignant
      transformation.

PMID- 11453811
TI  - Agminated atypical (dysplastic) nevi: case report and review of the literature.
AB  - BACKGROUND: Patients with the atypical mole syndrome have multiple dysplastic
      nevi that appear to be randomly distributed on certain preferred anatomical sites
      such as the upper back. These dysplastic nevi are thought to be acquired
      melanocytic nevi that begin appearing at puberty. To our knowledge, the presence
      of agminated atypical (dysplastic) nevi has not been reported. OBSERVATION: We
      describe a patient with the atypical mole syndrome who has more than 100
      melanocytic nevi, many of which are clinically atypical and one of which proved
      to be a melanoma. Among his many melanocytic nevi is a cluster of approximately
      50 nevi that are distributed in an area measuring 5 x 3 cm. The histopathologic
      features of these nevi are consistent with the diagnosis of "dysplastic nevus."
      CONCLUSIONS: To our knowledge, agminated atypical (dysplastic) nevi have not been
      described previously. The presence of agminated atypical (dysplastic) nevi in a
      patient with the atypical mole syndrome can be theorized to arise because of loss
      of heterozygosity.

PMID- 11453812
TI  - Detection of clinically amelanotic malignant melanoma and assessment of its
      margins by in vivo confocal scanning laser microscopy.
AB  - BACKGROUND: Near-infrared confocal scanning laser microscopy (CSLM) represents a
      novel imaging technique for in vivo microscopic analysis of skin lesions,
      including pigmented lesions. OBJECTIVES: To investigate the feasibility of
      detecting a clinically amelanotic malignant cutaneous melanoma using CSLM and to
      explore the use of this technique for assessing its margins. PATIENTS AND
      METHODS: Two lesions from 2 patients were imaged and analyzed using CSLM. Sites
      suspected to represent melanoma or benign skin on CSLM were marked as such; then,
      biopsy specimens were obtained for diagnosis using conventional histological
      analysis. Both lesions were stained for melanin pigment and analyzed
      immunohistochemically for the expression of melanosomal markers. In 1 case, a
      biopsy specimen was also examined with electron microscopy. RESULTS: The images
      obtained using CSLM allowed recognition of an abnormal intraepidermal melanocytic
      proliferation that was distinctly different from normal skin. Comparison of the
      sites examined using CSLM and subsequently using conventional histological
      methods revealed that CSLM correctly identified intraepidermal melanoma and
      benign skin. Fontana-Masson stains and immunohistochemical and ultrastructural
      studies showed that clinically amelanotic melanoma cells contained melanosomes
      and rare melanin granules. CONCLUSIONS: We demonstrated, for the first time, the
      detection of clinically amelanotic melanoma using CSLM. This technique may aid in
      the early detection of clinically barely visible or nonpigmented melanomas and
      may facilitate preoperative noninvasive assessment of their margins.

PMID- 11453813
TI  - Improvement of Pyoderma gangrenosum and psoriasis associated with Crohn disease
      with anti-tumor necrosis factor alpha monoclonal antibody.
AB  - BACKGROUND: Infliximab is an anti-tumor necrosis factor alpha monoclonal antibody
      IgG effective in the treatment and maintenance of remission of active refractory
      Crohn disease and associated draining enterocutaneous fistulae. Multiple
      infusions of infliximab show promising results in patients with rheumatoid
      arthritis. Currently, there is limited clinical experience with infliximab, and
      no published reports exist on its use in cutaneous disorders. OBSERVATIONS: We
      describe 2 patients with Crohn disease and pyoderma gangrenosum and 1 patient
      with Crohn disease and psoriasis who were treated with infliximab for
      recalcitrant Crohn fistulae, with concurrent improvement in their skin diseases.
      CONCLUSIONS: These cases suggest that infliximab, a promising therapeutic agent
      for refractory Crohn disease and fistulae, may also be effective in the treatment
      of pyoderma gangrenosum and psoriasis associated with Crohn disease.

PMID- 11453814
TI  - A brief history of dermatology in Iran.

PMID- 11453815
TI  - Baldness and coronary artery disease: the dermatologic point of view of a
      controversial issue.
AB  - OBJECTIVE: Several articles, most of them written by nondermatologists, have
      stressed that bald men have a higher risk for coronary artery disease than men
      who are not bald. This study was performed to evaluate the validity of such
      conclusions from a dermatologic point of view. DESIGN: A review of the 24
      articles in literature from 1954 to 1999 as provided by MEDLINE and a previous
      review. RESULTS: Five articles contained simple comments; 1 was a review of the
      previous literature; and 3 dealt only with the lipid profile. The remaining 15
      articles dealt with coronary artery disease and baldness, and 9 of these
      concluded that there is a relationship between the 2 conditions, especially in
      younger subjects with severe early-onset androgenetic alopecia. CONCLUSIONS:
      Baldness did not coincide with androgenetic alopecia in some of the articles
      examined, which makes it difficult to settle the issue. Subjects who develop
      baldness before their 30s may have a higher risk for coronary artery disease than
      other men, and they may be individuals with early-onset androgenetic alopecia who
      also present with particularly elevated dihydrotestosterone-testosterone ratios.
      The baldness theory should be included as a secondary hypothesis in large
      epidemiological studies of coronary artery disease. Such studies should include
      dermatologic expertise for accurate, cost-effective evaluation of baldness.

PMID- 11453817
TI  - From inflammation to neoplasia: mycosis fungoides evolves from reactive
      inflammatory conditions (lymphoid infiltrates) transforming into neoplastic
      plaques and tumors.

PMID- 11453818
TI  - Etanercept-induced injection site reactions: mechanistic insights from clinical
      findings and immunohistochemistry.

PMID- 11453820
TI  - Off-center fold: indurated plaques on the arms of a 52-year-old man. Diagnosis:
      Cutaneous reaction to phytonadione injection.

PMID- 11453821
TI  - Off-center fold: necrotizing livedo reticularis. Diagnosis: primary hyperoxaluria
      type I.

PMID- 11453822
TI  - Off-center fold: palpable purpura on the extremities. Diagnosis: leukocytoclastic
      vasculitis mimicking Janeway lesions of bacterial endocarditis.

PMID- 11453823
TI  - Off-center fold: multiple papulonodular lesions on the arm. Diagnosis: metastatic
      melanoma of unknown primary origin.

PMID- 11453824
TI  - Association between zalcitabine therapy for human immunodeficiency virus and
      granuloma annulare?

PMID- 11453825
TI  - Some articles should just not be published.

PMID- 11453826
TI  - Bullous pemphigoid associated with Castleman disease.

PMID- 11453828
TI  - Cytokine production profile of peripheral blood mononuclear cells in patients
      with large-plaque parapsoriasis.

PMID- 11453829
TI  - Black tongue.

PMID- 11453830
TI  - Postsurgical dermal lymphedema clinically mimicking inflammatory breast
      carcinoma.

PMID- 11453831
TI  - Squaric acid dibutylester: indications for use and efficacy in alopecia areata.

PMID- 11453838
TI  - Electronic journals: are they a paradigm shift?
AB  - Ejournals are becoming an accepted and necessary means of meeting the demands for
      the dissemination of knowledge. This introductory article discusses the recent
      "explosion" of ejournals and provides an explanation of what is meant by an
      "ejournal." Ejournals are explored within the traditional context of scholarship
      and a discussion of the "serials crisis" that promoted the inception of ejournals
      is presented. After laying the groundwork for discussing scholarship in this new
      age of dissemination of scholarly information, the article discusses whether this
      digital form of publication can be called a "paradigm shift" in Kuhn's (1970)
      traditional sense of the word.

PMID- 11453839
TI  - Electronic publishing: the movement from print to digital publication.
AB  - This article provides an overview of electronic publishing, describes how
      information increasingly is being exchanged within the scientific community, and
      discusses the scholarly qualifications of electronic venues. The following
      content is included: a.definition of electronic publishing; b.uses and types of
      electronic publishing; c.uses of electronic journals in nursing and health care;
      d.advantages and disadvantages of electronic journals; e.advantages and
      disadvantages of print journals; and f.the authors' projections for the future.
      Hotlinks to a variety of Internet resources on electronic resources are
      integrated throughout the article.

PMID- 11453840
TI  - The economics of electronic journals.
AB  - High print journal subscription costs, access to desktop publishing software, and
      awareness of Internet capability are among several reasons that interest in the
      electronic publishing of scholarly journals is increasing rapidly. The economic
      considerations of electronic publishing are not as familiar, however, although
      the fingertip accessibility of electronic journals, and in some cases, the lack
      of subscription charges gives the impression that electronic journal publishing
      is a much less costly means of publishing. Such an impression receives qualified
      confirmation in this article as an overview of the costs of scholarly publishing
      is provided, and the costs of print and electronic journals are compared. Also
      addressed are ways to recover costs of publishing electronic journals, and
      predictions for the future of such journals.

PMID- 11453841
TI  - Some do's and dont's in establishing your electronic journal.
AB  - The purpose of this article is to provide you with informative tips and things to
      think about that may help you get your new electronic journal off on the right
      screen. This new communication medium can seem overwhelming at first, but the
      goal is the same as always   communicate/disseminate/learn   soon it should seem
      like an old friend. Described herein are some quick do s and don ts, tips and
      pointers, and questions that should help you get a jump-start and help make
      establishing an electronic journal an enjoyable and exciting venture, while
      keeping the technological downside to a minimum.

PMID- 11453842
TI  - Development of an online journal.
AB  - This article describes the historical development of an electronic nursing
      journal, (OJIN), from inception to reality. Planning focused on a needs analysis
      for an electronic journal, audience and marketing concerns, editorial board
      membership, and financing of the journal. Included are recommendations for those
      considering starting an online journal.

PMID- 11453843
TI  - Nursing around the world: Australia.
AB  - Early nursing in Australia was influenced strongly by the British nursing
      tradition, characterized by an apprenticeship style of nurse education. However,
      this influence has been replaced by the transfer of all registered nursing
      education into the higher education sector. This article will discuss the
      development of the discipline of nursing in Australia as well as the Australian
      health care system and nursing work force. Nursing educational programs,
      registration, organizations, and research will be will be described. Finally
      current issues in Australian nursing and health care will be presented.

PMID- 11453844
TI  - Nursing around the world: Japan - preparing for the century of the elderly.
AB  - Japanese society, highly modern, yet traditional, is undergoing change due to
      economic and demographic pressures. The aging of the population has placed
      tremendous strains on its universal health and social service systems. The
      nursing profession is responding to these societal changes by its involvement in
      policy decisions and service enhancements for the elderly, and by increasing the
      educational level of nurses. In this article, nursing education, practice, and
      research as well as demographic trends in Japan are described.

PMID- 11453845
TI  - A perspective of nursing in Zimbabwe.
AB  - This article describes nursing in Zimbabwe within the context of primary health
      care, delineating various levels of delivery of nursing practice, educational
      preparation levels and implications for practice. This picture is intended to
      capture the quality of nursing care that is congruent to clients' expectations of
      the ever-changing Zimbabwean society. Nursing programs at various levels include
      health assessment, nursing process and nursing research. Clinical specialization
      including functional majors such as nursing education, nursing administration as
      well as health economics and budgeting have greater emphasis at the Masters
      level. The practice of nursing assists individuals, groups and communities to
      attain the ability to exercise their self-care to enhance health promotion.

PMID- 11453846
TI  - Practice development credentialing in the United Kingdom - a unique framework for
      providing excellence, accountability and quality in nursing and healthcare.
AB  - This paper will describe the purpose, process and value of an international
      Practice Development Program by which clinical units can choose to be
      credentialed. It will describe how the fourteen criteria that a Unit is
      credentialed against takes them along a journey of practice, personal and
      professional development that equips them to not only positively respond to, but
      to proactively influence, the challenges and changes that healthcare is facing
      globally. It explains how The Program focuses on credentialing sustainable
      practice development that then contributes to the development of both the
      capability and capacity of healthcare services. As a result, it crosses
      professional and organisational boundaries and constraints and concentrates on
      their shared purpose, delivering excellent patient care.

PMID- 11453848
TI  - Prerequisites and priorities for nursing research in Israel.
AB  - This article describes prerequisites and priorities for nursing research in
      Israel. The historical development of nursing research in Israel details shifts
      in types of research by decade from the 1960s through 1990s. The four phases of
      development and evaluation of nursing research are explored. Prerequisites for
      the development and growth of nursing research in Israel, as is true worldwide,
      include individual, professional, institutional and federal commitments.
      Priorities for Israeli nursing research include the development of a master plan
      which reflects its unique culture and geography.

PMID- 11453849
TI  - Quality of cataract surgery.

PMID- 11453850
TI  - Simultaneous management of blood flow and IOP in glaucoma.
AB  - Factors other than intraocular pressure (IOP) elevation must be involved in
      initiation and progression of glaucoma. An additional element in disease
      causation may be ischemia in the retina and optic nerve head. Ischemic damage to
      neurons in the CNS is similar mechanistically and histopathologically to changes
      seen in glaucoma. Further, glaucoma patients with normal IOP show clear evidence
      for cerebral and ocular ischemia. Aging and atherosclerosis reduce the ability of
      the eye to autoregulate blood flow when ocular perfusion pressure changes: the
      dependence of blood flow on perfusion pressure links ischemia to IOP.
      Consequently, neuroprotective treatments for glaucoma should be designed to both
      reduce IOP and improve ocular nutrient delivery.

PMID- 11453851
TI  - Age-related utilisation of cataract surgery in Sweden during 1992-1999. A
      retrospective study of cataract surgery rate in one-year age groups based on the
      Swedish National Cataract Register.
AB  - PURPOSE: To study the utilisation and increase of first eye cataract surgery in
      one-year age groups between 60 and 90 years of age during 1992-1999. METHODS:
      Data was extracted from the National Swedish Cataract Register (NCR) that covers
      about 93.2% of all cataract extractions performed in Sweden during 1992-1999. The
      total number of living persons in each one-year age group was collected from the
      Year Book of Statistics in Sweden (1993-2000). RESULTS: The number of cataract
      extractions in Sweden increased by 54.8% from 1992 to 1999. The rates of first
      eye cataract surgery in one-year age groups between 60 and 90 years of age were
      different for females and males and this difference did not change during a 37%
      increase of the surgery volume from 1992 to 1999. The rate of first eye cataract
      surgery increased significantly both for females (+29.4%) and males (+27.2%)
      during 1992 to 1999 in Sweden. CONCLUSION: The rate of first eye cataract surgery
      increased significantly from 1992 to 1999 but the gender difference in age
      related utilisation of surgery remained unchanged. The increase in rate was about
      the same in all age groups.

PMID- 11453852
TI  - Gender and referral to cataract surgery in Sweden.
AB  - PURPOSE: To investigate how cataract surgery was initiated and analyse possible
      gender difference in referral to surgery. METHODS: Consecutive patients scheduled
      for first eye cataract surgery at three Swedish community-run eye departments
      were interviewed concerning how surgery was initiated. RESULTS: 649 patients were
      interviewed and 63.2% were female. The number of patients referred to surgery by
      an earlier contact with a health care provider was 271 (41.8%) and the remaining
      378 (58.2%) patients had actively requested advice or help because of visual
      problems caused by cataract and without a prior regular contact. 44.7% of female
      patients were referred through a health care provider they visited for reasons
      other than cataract and the corresponding number for male patients was 36.8%.
      This gender difference is statistically significant at the 5% level. CONCLUSION:
      A health care provider that patients visited for other problems than cataract
      referred female patients to cataract surgery to a significantly higher degree
      than male patients.

PMID- 11453853
TI  - Comparative study of vitrectomy for dropped nucleus with and without the use of
      perfluorocarbon liquid. Clinical, electrophysiological and visual field outcomes.
AB  - PURPOSE: To compare pars plana vitrectomy for dropped nucleus with and without
      perfluorocarbon liquid. METHODS: 24 eyes with dropped nucleus were randomized to
      undergo PPV with perfluorodecalin, (study, n=12) and without it (control, n=12).
      Visual acuity, IOP, visual evoked response and electroretinography were noted at
      study entry and up to 3 months after PPV. Humphrey perimetry was done at 3
      months. RESULTS: Final visual acuity was >20/60 in 75% of study eyes and 41.6% of
      controls. The two groups were statistically comparable with regard to the above
      parameters before PPV and during follow-up. The timing of vitrectomy did not
      significantly influence the final visual acuity. A higher rate of complications
      was seen in the control group. CONCLUSIONS: Perfluorodecalin facilitated the
      procedure and possibly minimized complications, and was found to be safe for
      intraoperative use in terms of recovery of visual acuity, stable ERG and VER, and
      normal visual fields.

PMID- 11453854
TI  - Clinical features and a follow-up study in a family with X-linked progressive
      cone-rod dystrophy.
AB  - PURPOSE: To study a large family with X-linked progressive cone-rod dystrophy.
      METHODS: There were 128 members in the family. Of these, 45 had an
      ophthalmological examination and 3 gave their permission to use the results of
      their recent ophthalmological examination. In addition to the usual eye
      examination, visual fields, colour vision, dark adaptation and electroretinogram
      (ERG) were examined. RESULTS: Ten affected men aged 6 to 81 years were found in
      the family. The visual acuities varied from counting fingers (cf) 10 cm to 0.5 in
      the right eye (RE) and from cf 30 cm to 0.4 in the left eye (LE). The refraction
      was myopic in all affected members, varying from -1.5 to -24.0 D (RE) and from 
      2.0 to -20.25 D (LE). In visual functions, central scotomas and concentric
      constriction in the visual fields, red or red-green defects in colour vision,
      abnormal cone and rod dark adaptation and affected cone response in ERG were
      found. The 6 obligate carriers were aged 17 to 77 years. Their visual acuities
      varied from 0.05 (strabismic amblyopia) to 1.25(RE) and from 0.7 to 1.25 (LE),
      and refraction from +/-0 to +6.0 D (RE) and from -0.5 to +5.0 D (LE). Their
      visual fields and colour vision were normal. The non-affected men were aged 13 to
      55 years, their visual acuity was normal in both eyes, and refraction varied from
      -5.0 to +1.5 D (RE) and from -5.5 to +1.75 (LE). The result of the eye
      examination was normal except in colour vision: two men were congenitally
      deuteranomalous. The women who were not obligate carriers were aged 10 to 77
      years, their visual acuity was from 0.3 to 1.6 in both eyes, and refraction from 
      5.5 to +4.75 (RE) and from -5.25 to +4.0 (LE). Two women had one amblyopic eye.
      Otherwise the eye examination was normal. CONCLUSIONS: The clinical diagnosis of
      X-linked cone dystrophy 1 (COD1) is based on progressive loss of visual acuity,
      moderate or high myopia, red colour vision defect and affected cone response or
      cone and rod response in ERG. The future identification of the COD1 gene will
      confirm the diagnosis of the disease and help in genetic counseling of the
      family.

PMID- 11453855
TI  - Cone photoreceptors in laminated retinal transplants.
AB  - PURPOSE: To investigate the contents of green- and blue-sensitive cone
      photoreceptors in laminated rabbit retinal transplants. METHODS: Eleven rabbits
      each received a sheet of embryonic neuroretina into the subretinal space in one
      eye. Vitrectomy was used in the procedure and properly polarized flat transplants
      were placed on the host pigment epithelium. After 17-309 days the transplants
      were examined immunohistochemically with specific antibodies against COS-1 (green
      sensitive cones) and OS-2 (blue-sensitive cones). RESULTS: All grafts displayed
      normal lamination with well developed photoreceptor outer segments apposed to the
      host retinal pigment epithelium. Occasionally, rosettes were found at the
      transplant edges. Both COS-1 positive and OS-2 positive cones were detected. In
      the laminated part of the grafts, COS-1 positive cones were more numerous than OS
      2 positive ones. In the rosetted parts of the transplants the relationship
      between the cones was reversed. CONCLUSION: Full-thickness embryonic rabbit
      retinal transplants develop into laminated retinas with well-developed
      photoreceptor outer segment. Both green- and blue-sensitive cone photoreceptors
      are present and the ratio between the two cone types is the same as in the normal
      adult rabbit retina.

PMID- 11453856
TI  - Interferon-alfa treatment of facial infantile haemangiomas: with emphasis on the
      sight-threatening varieties. A clinical series.
AB  - PURPOSE: To report on the efficacy of systemic Interferon-alfa therapy in
      controlling the endothelial proliferation in expanding facial haemangiomas of
      infancy threatening the eye. METHODS: The series comprised 9 subjects with facial
      haemangiomas of rapid growth within the first few months of life. All
      haemangiomas had relation to an eyelid and affected the visual access to the eye.
      At least three tumours were also intraorbital, and in one case the glottis was
      affected. Interferon-alfa was given subcutaneously in daily doses of 3 mio
      units/m2. Ophthalmic follow-up including ultrasound evaluation was done,
      initially with intervals of 4-8 weeks. RESULTS: Interferon-alfa was given over 9
      41 weeks (median duration 22 weeks) in cumulated doses of 63-287 million units.
      Progression was arrested in all and with a subsequent tumour regression
      considered accelerated as judged from earlier clinical giant haemangioma
      experience. A control series was not possible. One patient had systemic
      prednisone added over some weeks. Two infants reacted with a flu-like malaise. A
      premature infant developed a slight spastic diplegia. CONCLUSIONS: In the 9
      infants with growing ophthalmic haemangiomas we recorded a good response to
      systemic Interferon-alfa administered as daily doses by subcutaneous injection.
      In general the treatment appeared well tolerated. During clinical follow-up
      diagnostic ultrasound evaluation (the depth dimension) proved helpful; in
      particular there was a sparing effect on CT and MRI scans which require general
      anaesthesia.

PMID- 11453857
TI  - A Horner-like syndrome and cluster headache. What comes first?
AB  - PURPOSE: To evaluate if an ocular sympathetic lesion may be a prerequisite for
      cluster headache to occur. METHODS: Patients with a permanent Horner-like
      syndrome at the debut of cluster headache were identified from history and
      photographs. RESULTS: Among 57 patients with cluster headache, seven patients (5
      males and 2 females) exhibited a permanent Horner-like syndrome on the painful
      side when first seen at the outpatient department. During this study it was
      possible to get information from six of these patients and five of them had side
      constant cluster headache. In retrospect, these five patients had had a Horner
      like syndrome for years prior to the onset of ipsilateral cluster headache.
      CONCLUSION: The findings indicate that a sympathetic lesion or dysfunction may be
      a prerequisite for the subsequent development of cluster headache.

PMID- 11453858
TI  - Treatment of post-keratoplasty astigmatism by topography supported customized
      laser ablation.
AB  - PURPOSE: To evaluate the clinical and optical efficiency of topography modulated
      customized corneal ablations for irregular corneal astigmatism. MATERIAL &
      METHODS: Sixteen eyes of 16 patients with iatrogenic corneal astigmatism (post
      keratoplasty) were consecutively included. Based on preoperative corneal
      topographic measurements height deviations from a spherical corneal shape were
      calculated and transferred to a flying-spot excimer laser. Photo-refractive
      keratectomy of the topographic irregularities was then performed. Clinical and
      optical efficiency was evaluated by best corrected visual acuity and by
      computation of corneal wavefront aberrations before and up to one year after
      treatment. Wavefront aberrations were decomposed by Zernike polynomial analysis.
      RESULTS: Before treatment the average best-corrected visual acuity was 0.23.
      Three and 12 months after PRK the average best-corrected visual acuity had
      increased to 0.37 (p<0.05) and 0.45 (p<0.05), respectively. Corneal wavefront
      aberrations (root-mean-square) were 3.35 before surgery and 1.88 (p<0.05) and
      1.51 (p<0.05) at three and 12 months after treatment. Zernike polynomial
      decomposition of the wavefront aberrations revealed that regular corneal
      astigmatism was the most important aberration component before and after surgery.
      Regular astigmatism was significantly decreased by the procedure, whereas coma,
      spherical aberrations, and higher-order aberrations were not reduced
      significantly. CONCLUSION: Topography modulated photorefractive keratectomy of
      highly astigmatic corneal grafts can improve best corrected visual acuity and
      reduce corneal wavefront aberrations. Even in apparently irregular topographic
      astigmatism, regular astigmatic wavefront aberration may be the most important
      contributor to wavefront errors.

PMID- 11453859
TI  - Wound healing response in the presence of stromal irregularities after excimer
      laser treatment.
AB  - PURPOSE: To trace the fate of stromal irregularities after excimer laser
      treatment and to increase our knowledge of the reasons why surface irregularities
      in the ablation bed cause inferior postoperative results. METHODS: Twelve New
      Zealand White rabbits received a transepithelial photoablation to a preset depth
      of 60 microm. An electron microscopy specimen grid was then placed on the denuded
      stroma and another 20 microm ablation was applied in order to produce surface
      irregularities. Another six rabbits received a plano transepithelial
      photoablation to a preset depth of 80 microm. The treated corneas were harvested
      at various timepoints and differentially further processed for microradiography,
      hematoxylin-eosin -, hyaluronan (HA)- and leukocyte protein L1 staining. RESULTS:
      In the grid treated corneas the subepithelial mesh pattern is clearly discernible
      after 1 week, and after 4 weeks it is replaced by a subepithelial layer
      containing HA and water. The thinning of this layer between 1 and 12 weeks is
      statistically significant (p<0.05). After 4 and 8 week the plano treated corneas
      only exhibit some subepithelial HA- and water accumulation. After 1 day the grid
      treated corneas show an extensive stromal infiltration of leukocytes. In the
      plano treated corneas the leukocytes mainly remain on the surface. CONCLUSIONS:
      During the healing process stromal irregularities are flattened, leaving a
      homogeneous zone with increased water content. This subepithelial layer is
      rarefying as new subepithelial tissue is forming. Postablational irregularities
      induce a more pronounced healing reaction when compared to a smooth ablation
      surface. Leukocyte infiltration seems to play a role in this process.

PMID- 11453860
TI  - A previous abrasion in the contralateral eye influences the cell kinetics during
      healing of a central corneal abrasion.
AB  - PURPOSE: To study the influence of a previous erosion in the fellow eye on the
      proliferative response during healing of a central corneal erosion. METHODS: A
      corneal abrasion was made on the right eye of 20 rats. After 1 week a corneal
      erosion was made in the left eye of the pre-treated animals and in 20 previously
      untreated animals. Cell kinetic methods were used to estimate the labelling index
      (LI) and the mitotic rate (MR) after 1, 2, 4, 6 and 12 days. RESULTS: After 24
      hours the corneal erosions were covered by epithelial cells in 3 of 4 animals in
      both groups. The LI and the MR were significantly higher in the pre-treated group
      on the 2nd day after erosion. CONCLUSIONS: The proliferation measured by LI and
      MR was increased when an abrasion was made in the contralateral eye 1 week
      earlier. This might explain the faster healing rate of the second eye reported by
      other authors (Rask et al. 1996). The healing process in the cornea is modulated
      by systemic influence.

PMID- 11453861
TI  - Small incision trabeculectomy: experiences with this new procedure for glaucoma
      surgery in Indian eyes.
AB  - PURPOSE: The purpose of this study was to evaluate the potential advantages and
      disadvantages, success rate and complications of this new procedure for glaucoma
      surgery, which includes the formation of a filtration fistula without any
      dissection of the Tenon's capsule; as an alternative to trabeculectomy with or
      without pharmacological wound modulation. METHODS: Small Incision Trabeculectomy
      avoiding Tenon's capsule was performed in 40 glaucomatous eyes through a 2.5 mm
      limbal incision and intraocular pressure was monitored serially over a period of
      12 months. RESULTS: The mean postoperative intraocular pressure (16.60+/-5.93
      mmHg) at 12 months follow-up was significantly lower than the mean preoperative
      IOP (30.20+/-10.70 mmHg). Thirty-six eyes (90%) had IOP less than 22 mmHg without
      antiglaucoma medications at the end of the 12-month follow-up. Blebs were pale
      and diffusely elevated. No serious complications were encountered. CONCLUSION:
      This new technique is a low-cost and safe alternative to conventional
      trabeculectomy that effectively reduces intraocular pressure. The use of a small
      2.5 mm incision which obviates the dissection of the Tenon's capsule and
      subsequent subconjunctival fibrosis, the absence of requirement of any
      sophisticated instruments, and the absence of any major complications which are
      encountered with the use of anti-metabolites entails that this procedure be
      performed more often in glaucomatous eyes needing filtration surgery.

PMID- 11453862
TI  - Polarimetric nerve fiber analysis in patients with peripapillary myelinated
      retinal nerve fibers.
AB  - PURPOSE: The aim of this study was to compare the RNFL thickness in eyes with
      myelinated retinal nerve fibers (MRNF) and age, sex-matched controls using
      scanning laser polarimetry. METHODS: Seventeen patients with MRNF underwent a
      comprehensive ophthalmological examination including automated visual field
      testing, and scanning laser polarimetry with Nerve Fiber Analyser (NFA II).
      Twenty eyes with MRNF from 17 patients were available for the study. Sixteen
      healthy, age and sex-matched subjects were taken as controls. Retinal nerve fiber
      thickness measurements of the four sectors (superior, inferior, nasal, temporal)
      and along the whole circumference of the optic disc were obtained for affected
      and control eyes, and compared. RESULTS: Inferior average and inferior integral
      parameters of the NFA revealed significantly thinner RNFL thickness measurements
      in eyes with inferiorly located MRNF compared to controls. CONCLUSION: Retinal
      myelination alters the birefringent property of the RNFL, and results in
      diminished thickness measurements. Hence, NFA measurements in patients with MRNF
      may not be reliable.

PMID- 11453863
TI  - Scanning laser polarimetry versus frequency-doubling perimetry and conventional
      threshold perimetry: changes during a 12-month follow-up in preperimetric
      glaucoma. A pilot study.
AB  - PURPOSE: To evaluate the possibility for detecting the progression in
      preperimetric primary open angle glaucoma (POAG) using scanning laser polarimetry
      (SLP), frequency-doubling technology (FDT), and conventional automated perimetry
      (AP). PATIENTS AND METHODS: 22 eyes of 11 preperimetric POAG patients were
      evaluated using SLP (Nerve Fiber Analyzer, GDx), AP (Humphrey 24-2 threshold
      test) and FDT (30 degrees threshold test). All eyes had intraocular pressure
      (IOP) higher than 21 mmHg before treatment, but were consistently lower than 22
      mm Hg with unchanged topical medication before and during the study. At the
      initial evaluation session optic nerve heads showed mild glaucomatous changes but
      the visual fields were normal (MD better than 2.0 dB, Glaucoma Hemifield Test:
      within normal limits or borderline). AP and FDT measurements were repeated 6
      months later, and all three tests were repeated 12 months after the first
      investigation. RESULTS: IOP, AP and FDT measurements showed no statistically
      significant changes during the 12-month follow up period. In contrast to this, a
      tendency for a glaucomatous type decrease was seen with SLP in the retinal nerve
      fibre layer (RNFL) thickness parameters (mean superior and inferior sector
      thickness values, ellipse average thickness and maximal modulation). The mean
      decrease of RNFL thickness in the superior and inferior sectors was 2.77 microm
      and 2.48 microm, respectively. Using the two-way nested ANOVA, which considers
      the relation between the right and left eyes of the subjects, the decrease was
      statistically significant (p=0.021) for the inferior sector RNFL thickness.
      CONCLUSION: The results suggest that scanning laser polarimetry is a useful
      technique to detect and measure glaucomatous progression in early glaucoma.
      Scanning laser polarimetry of the RNFL may help to detect and quantify early
      progression even if worsening is not seen with perimetry and FDT tests.

PMID- 11453864
TI  - Ocular and orbital cysticercosis.
AB  - PURPOSE: To study the demographic factors, clinical diagnosis, results of
      investigation, modalities of treatment and their outcome in ocular and
      extraocular cysticercosis. METHOD: A total of 20 patients were recruited for the
      study. Ultrasonography and computed tomography were done for all the patients.
      Serial ultrasound was obtained in patients receiving medical treatment. Therapy
      was individualized according to the location of the cyst. RESULTS: The commonest
      clinical presentation was proptosis (9 of 20) with restriction of ocular
      movements, followed by subconjunctival cyst, subretinal cyst, papilloedema,
      atypical optic neuritis, lid nodule and intraretinal cyst. Ultrasonography was
      comparable with computed tomographic scan for detection of scolex. Two of the
      twenty patients had associated cysts in the brain parenchyma. Medical or surgical
      therapy as indicated, had a satisfactory outcome. CONCLUSION: Cysticerci can
      lodge themselves in any part of the ocular and extra ocular tissue. Associated
      brain parenchyma involvement is quite rare. The clinical presentation, treatment
      and outcome mainly depends on the location of the cyst.

PMID- 11453865
TI  - Increased permeability of the blood-aqueous barrier after panretinal
      photocoagulation for proliferative diabetic retinopathy.
AB  - PURPOSE: To measure the permeability of the blood-aqueous barrier before and
      after panretinal photocoagulation (PRP) in patients with proliferative diabetic
      retinopathy. METHODS: Twenty patients with diabetic proliferative retinopathy in
      one eye and background retinopathy in the other eye were included. PRP was
      performed in the proliferative eye, while the other eye served as control.
      Aqueous flare intensity was measured with a laser flare cell meter before, 10 and
      90 days after treatment. RESULTS: The flare was stable in the control eye with a
      flare of 4.5+/-2.3, 4.4+/-2.4, and 4.5+/-1.7 photon counts/ms (mean+/-standard
      deviation) on Day 0, 10 and 90. In the laser treated eye corresponding figures
      were 5.2+/-2.4, 9.6+/-3.3, and 7.1+/-2.8 photon counts/ms, with a significant
      increase in aqueous flare at 10 days (p<0.001) and 90 days (p=0.002). CONCLUSION:
      A significant increase in aqueous flare was found 10 days after PRP, indicating a
      breakdown of the blood-aqueous barrier after retinal laser treatment. The
      breakdown was still present, however, less pronounced, after 3 months.

PMID- 11453866
TI  - Long-term follow-up of idiopathic central serous chorioretinopathy without laser.
AB  - PURPOSE: The purpose of this study was to observe the varied types of
      manifestations in the fundus of patients with idiopathic central serous
      chorioretinopathy (ICSC) without laser treatment and also to assess the ultimate
      visual outcome in such cases in a long-term follow-up ranging from 7 to 23 years.
      METHODS: This study is confined to 5 selected cases of ICSC which fairly
      represent the different types of late stage manifestations of the disease in the
      fundus. Case records from our hospital, as well as available records of previous
      treatment elsewhere were reviewed. A complete ophthalmological examination,
      routine laboratory investigations and fluorescein fundus angiography (FFA) were
      repeated in each case on the day of final evaluation. RESULTS: Pigmentary
      disturbances in the macular area resembling to some extent age-related macular
      degeneration (AMD), extensive retinal pigment epithelial (RPE) atrophy and
      macular haemorrhage have been observed in the fundus of the reviewed cases.
      CONCLUSIONS: ICSC runs an unpredictable course and there are no definitive
      clinical clues to predict its ultimate outcome. Recurrence of the condition is a
      possibility for a considerable period of time.

PMID- 11453867
TI  - The influence of level and polarity of figure-ground contrast on vision.
AB  - PURPOSE: To document the effect upon human foveal vision of changes in the level
      and polarity of figure-ground contrast under photopic controlled test conditions,
      with particular emphasis on performance at low contrast levels. METHODS: Using a
      forced-choice psychophysical paradigm, threshold acuity estimates were derived at
      9 discrete levels over a near-3 octave contrast range for Landolt ring-type
      stimuli of either positive or negative polarity. Data were obtained under
      binocular conditions from 10 young adults, each wearing their optimum low myopic
      spectacle correction. RESULTS: Visual acuity declined linearly with reducing
      stimulus contrast, the deterioration increasing substantially at <10% figure
      ground contrast regardless of stimulus polarity. Performance was slightly (but
      not statistically significantly) better for positive contrast stimuli.
      CONCLUSION: Irrespective of contrast polarity, a reduction in stimulus figure
      ground contrast <10% produces an accelerated decrement in photopic foveal vision
      compared to the performance at levels >10%. Some clinical and practical
      implications of this outcome are considered with regard to the examination of
      patients with normal and compromised visual function.

PMID- 11453868
TI  - Thyroid-associated orbitopathy developed during hormone replacement therapy.
AB  - Thyroid-associated orbitopathy (TAO) developed in relation to estrogen combined
      with progesterone therapy has not been reported previously. We report a case of a
      56-year-old postmenopausal woman who during estrogen/progesterone treatment
      developed signs and symptoms of orbitopathy. The patient had no previous history
      of autoimmune- or thyroid disorders. The initial eye symptoms disappeared after
      withdrawal of hormone replacement therapy. Five years later estrogen/progesterone
      treatment was re-instituted. The patient had relapse of orbitopathy. The hormones
      were discontinued and the eye symptoms disappeared again. This suggests that
      estrogen and/or progesterone could be of some pathogenetic importance in the
      induction of orbitopathy

PMID- 11453869
TI  - Presumed sertraline maculopathy.
AB  - PURPOSE: To report a unique case of a woman who developed simultaneous bilateral
      maculopathy presumed to result from intake of sertraline hydrochloride, a
      serotonin reuptake inhibitor. METHODS: Full clinical ocular examination, color
      vision testing, automated static perimetry, electroretinography,
      electrooculography and fundus fluorescein angiography were performed. Living
      members of her family were also examined. RESULTS: The patient had normal
      electroretinography and electrooculography results. Automated static perimetry
      showed generalized reduction of sensitivity and central scotomas. Macular lesions
      resolved 6 months after discontinuation of sertraline, however, during twenty
      months of follow-up her visual acuity and abnormalities in other psychophysical
      tests did not improve. CONCLUSION: Patients started on sertraline should be
      informed of the potential risk of developing maculopathy, and they should be
      examined regularly to detect possible early alterations.

PMID- 11453870
TI  - Implantable total artificial heart developed by Abiomed gets FDA approval for
      clinical trials.

PMID- 11453871
TI  - Effects of a vitamin E-modified dialysis membrane and vitamin C infusion on
      oxidative stress in hemodialysis patients.
AB  - Hemodialysis deteriorates oxidative stress. Vitamin E is an antioxidant whose
      regeneration is provided for by vitamin C. The authors tested the effects of a
      vitamin E-modified membrane (E), nonmodified cellulose membrane (O), and vitamin
      C infusion (500 mg, C) into the arterial blood line during dialysis on parameters
      of oxidative stress. In a short-term study, 24 patients were subjected to a
      single dialysis session with E, O, E with C, and O with C protocols. In a long
      term study (12 weeks), 20 patients were randomized into groups with C and without
      C on each dialysis, and both groups had dialysis using O, E, and again O membrane
      for 4 weeks each. In the short-term study, thiobarbituric acid reacting
      substances (TBARS) in plasma rose after dialysis (p < 0.02) with O, and no
      changes were observed in the other 3 protocols. In the long-term study,
      predialysis TBARS declined when using E both in the groups with C (p < 0.02) and
      without C (p < 0.05). A switch over to O resulted in TBARS returning to baseline
      levels. The E membrane prevented an increase in lipid peroxidation during single
      dialysis, and long-term use of the E membrane also resulted in a decrease in the
      predialysis lipid peroxidation level. The antioxidant capacity of the E membrane
      was not enhanced by vitamin C infusion. High doses of vitamin C administered
      during dialysis using a nonmodified cellulose membrane prevented an increase in
      lipid peroxidation, most probably due to the enhanced rate of endogenous vitamin
      E regeneration.

PMID- 11453872
TI  - Red eye syndrome: clinical and experimental experience in a new aspect of diffuse
      eosinophilic infiltration?
AB  - Twenty-two of 24 hemodialysis patients dialyzed simultaneously with a new batch
      of cellulose acetate dialyzers promptly developed a spectrum of symptoms and
      physical signs including red eyes, hearing loss, tinnitus, and bone pain,
      previously described as red eye syndrome. We subsequently injected 4 rabbits with
      an eluate from a dialyzer of the same or a control batch. Six hours following
      exposure, the animals developed, in addition to red eyes, diffuse eosinophilic
      infiltration of various organs as well as myopathic changes and moderate brain
      edema. On the basis of these data, we suggest that it cannot be concluded whether
      the underlying pathophysiological mechanisms were toxic, allergic or both and
      that the occurrence of relevant symptomatology in 2 or more simultaneously
      dialyzed patients is a strong argument against unnecessary diagnostic or
      therapeutic procedures. Finally, a second exposure in a given patient should be
      avoided.

PMID- 11453873
TI  - Polymethylmethacrylate efficacy in reduction of renal itching in hemodialysis
      patients: crossover study and role of tumor necrosis factor-alpha.
AB  - Pruritus is one of the major unsolved problems for patients receiving regular
      hemodialysis. In this study, we conducted a 6 month prospective and crossover
      trial to investigate the effect of polymethylmethacrylate (PMMA) membrane for
      renal itching. We also examined the role of the tumor necrosis factor (TNF)-alpha
      system for pruritus in hemodialysis patients. We assessed the degree of skin
      itching and measured circulating levels of TNF-alpha and soluble TNF receptors
      (sTNFR-I, sTNFR-II) in 19 patients using hemodialysis, complicated by prolonged
      severe pruritus for 6 months. Serum sTNFR-I and II levels were significantly
      elevated in hemodialysis patients compared to normal subjects. Serum sTNFR-II
      levels were significantly and negatively correlated with serum albumin (r = 
      0.602, p = 0.007). A significant positive relationship was also found between
      sTNFR-I and erythropoietin dosage (r = 0.554, p = 0.016). However, no association
      was found between the degree of pruritus and circulating sTNFR-I and II values.
      Skin itching scale was significantly decreased from 2.7 +/- 0.2 to 2.1 +/- 0.3
      following the use of PMMA membrane for 3 months (p < 0.05). In contrast, there
      was no change in itching scales during 3 months of conventional therapy (2.2 +/-
      0.3 versus 2.2 +/- 0.3, p = NS). PMMA itself did not affect serum TNF-alpha and
      sTNFR values as well as conventional dialyzer membranes. These findings suggested
      that the PMMA dialyzer can improve renal itching not mediated through the
      modification of the TNF-alpha system.

PMID- 11453874
TI  - Atherosclerosis risk is higher in continuous ambulatory peritoneal dialysis
      patients than in hemodialysis patients.
AB  - While it has been reported that myocardial infarction and cerebrovascular disease
      are more common in continuous ambulatory peritoneal dialysis (CAPD) patients than
      in hemodialysis patients, some studies have not supported these results. The aim
      of this study was to compare CAPD and hemodialysis patients with regard to
      atherosclerotic changes and to assess which factors might be responsible for
      atherosclerosis in dialysis patients. Group 1 consisted of 65 CAPD patients, and
      Group 2 consisted of 109 hemodialysis patients who were age-, gender-, and
      duration-of-dialysis-matched with CAPD patients. We used ultrasonographic
      measurement of carotid artery intima media thickness to identify atherosclerosis.
      Known risk factors for atherosclerosis including hypertension, smoking, serum
      levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol
      (LDL-C), high-density lipoprotein cholesterol, lipoprotein (a) [Lp(a)], albumin,
      intact parathormone, fibrinogen, and C-reactive protein were determined in all
      patients. More atherosclerotic changes were seen in CAPD than in hemodialysis
      patients. Of all the atherosclerosis risk factors, only serum total cholesterol,
      LDL-C, and Lp(a) levels were significantly higher in patients on CAPD.

PMID- 11453875
TI  - Comparative analysis of human serum albumin adsorption and complement activation
      for intraocular lenses.
AB  - Intraocular liquid, in contrast to blood, has no cellular components; therefore,
      proteins (human serum albumin [HSA], and [alpha, beta, gamma] globulins) are the
      major components that determine patients' response to the intraocular lens (IOL)
      surface. In addition to the amount of adsorbed proteins, the possibility of its
      conformational changes, including conformational changes of globulins C1 and C3
      that respond for the activation of the complements system by the classical and
      alternative pathways, cannot be excluded. The interaction between IOLs and
      protein components of intraocular liquid directly influences the ocular exudative
      reaction in the early postoperational period, the intensity of cellular and
      pigmental scurf on the surface of the IOLs, and the state of endothelial cells of
      the cornea in the distant postoperational period. Our goal was to compare the
      interaction of commercial IOLs made from polymethylmethacrylate, silicone, poly-2
      hydroxyethyl methacrylate (p-HEMA), and copolymer p-HEMA with collagen with HSA
      and the complement system. The total internal reflection fluorescence (TIRF)
      method and hemolytic assay were used for this task, respectively. It has been
      demonstrated that the probability of biocompatibility of commercially produced
      IOLs on the stage of protein adsorption can be evaluated using the kinetic of HSA
      fluorescein isothiocyanate adsorption onto the IOL surface by the TIRF METHOD: In
      the case of IOLs from p-HEMA, a negative correlation was shown between the degree
      of irreversible adsorption of HSA and the minimum relative rate constant of the
      surface-induced complement activation. We did not find any correlation between
      hydrophilicity/hydrophobicity of lenses and their adsorptional properties
      including complement activation. From suggested adsorptional criteria in vitro
      for biocompatible surfaces, the hydrogel lens from p-HEMA has a lower probability
      of biocompatibility in comparison with other IOLs.

PMID- 11453876
TI  - A bone replaceable artificial bone substitute: osteoinduction by combining with
      bone inducing agent.
AB  - Bone inducing agent (BIA) isolated from Saos-2 human osteosarcoma cells was added
      to an artificial bone substitute composed of 980 degrees C-heated carbonate
      apatite (CAp) and Type I atelocollagen (AtCol) extracted from bovine tail skins
      (88/12 in wt/wt %), and a CAp-AtCol-BIA substitute was prepared as an
      osteoinductive bone substitute. Rat calvaria osteoblasts treated by the isolated
      BIA demonstrated significantly increased alkaline phosphatase (ALP) activity
      after 3 days (p < 0.05). In vitro cell attachment and proliferation and ALP
      activity were investigated for the bone substitute combined with BIA. Osteoblasts
      cultured onto the surface of the CAp-AtCol-BIA substitute demonstrated remarkable
      morphological changes such as radial spreading, flattening, and projecting
      filopodia after 5 days. In comparison with the substitute without BIA,
      osteoblasts grown in the BIA-combined CAp-AtCol substitute expressed
      significantly increased proliferation and ALP activity, respectively (p < 0.05).
      Both the substitutes combined with and without BIA were implanted into artificial
      defects created in rabbit radii. After 4 weeks, the CAp-AtCol-BIA substitute
      implanted lesion was completely replaced by regenerated host bone in radiological
      observation whereas the substitute without BIA was partially resorbed. No
      histologic abnormalities appeared in the substitute either with or without BIA.

PMID- 11453877
TI  - Functional and biological test of a 20 channel implantable stimulator in sheep in
      view of functional electrical stimulation walking for spinal cord injured
      persons.
AB  - A newly developed implantable stimulator with 20 output channels, mainly intended
      for the stimulation of lower extremities in paraplegics, was implanted in 6 sheep
      over a time period of 26 weeks. Five epineural electrodes each were used to
      contact various nerves at different locations to elicit hip and knee extension
      and flexion and to make carrousel and selective stimulation possible. Different
      electrode application strategies in view of paraplegic standing and walking were
      investigated. Additional implanted electrodes allowed M-wave monitoring for
      selectivity investigations in 3 sheep. Stimulator, electrode leads, and
      electrodes proved to be reliable. Selective stimulation with electrodes placed on
      the trunk of the sciatic nerve could be demonstrated but with bad
      reproducibility. Histological investigation of the tissues surrounding electrodes
      and leads showed the expected stable foreign body response. Strong hip and knee
      extension could be gained in all cases while only weak flexion forces could be
      elicited in most cases. Muscle biopsies showed that daily stimulation for 8 h at
      threshold level caused an increase in muscle Type I fibers and a decrease in Type
      IIc fibers. Implants and electrodes fulfill the most important functional and
      biological criteria for their clinical application for paraplegic walking. The
      intention to provide selective flexion functions via epineural stimulation could
      not be demonstrated sufficiently in this animal model.

PMID- 11453878
TI  - The effect of circuit surface area on CD11b(mac-1) expression in a rat
      recirculation model.
AB  - The aim of the study was to assess the effect of exposed surface area of
      diethylhexylphthalate plasticized polyvinylchloride (PVC) on the expression of
      the adhesion molecule CD11b(mac-1) on neutrophils and to determine whether there
      is any apparent advantage in the current trend in reducing circuit surface area
      in terms of neutrophil activation. The study was carried out using a parallel
      plate rodent recirculation biomaterial testing model on 4 groups of 10 adult male
      Sprague Dawley rats weighing between 350 and 450 g. One group comprised the
      control group in which there was no biomaterial exposure. In the remaining 3
      groups, the animals were subjected to either high (48 cm2), intermediate (24
      cm2), or low (12 cm2) biomaterial surface area exposure. The parallel plate test
      cell was connected to the right femoral circulation and recirculation initiated
      at a flow rate of 1.5 ml/min for a period of 60 min. Blood samples were taken at
      0, 30, and 60 min for the assessment of CD11b expression. Cd11b was assessed
      using flow cytometric analysis on neutrophils. The results demonstrated that
      there was a surface area related effect in the upregulation of CD11b. The
      difference at the terminal sample point between the highest surface area group
      (293.95 +/- 18.57%) and the low surface area group (133.80 +/- 49.31%) was highly
      statistically significant (p < 0.001). These results demonstrate that there may
      be some gain in terms of reduced inflammatory response from reducing the exposed
      surface area of PVC in extracorporeal perfusion circuits.

PMID- 11453879
TI  - Heparin-coated extracorporeal circulation with full and low dose heparinization:
      comparison of thrombin related coagulatory effects.
AB  - Thrombin related coagulatory effects of a heparin-coated cardiopulmonary bypass
      system combined with full and low dose systemic heparinization were investigated
      in a prospective, randomized study in coronary bypass surgery patients. One
      hundred nineteen patients were divided into 3 groups. Group A (n = 39) had a
      standard uncoated extracorporeal circulation (ECC) set, and systemic heparin was
      administered in an initial dose of 400 IU/kg body weight. During ECC activated
      clotting time (ACT) was maintained at > or =480 s. Group B (n = 42) had the same
      ECC set completely coated with low molecular weight heparin. Intravenous heparin
      was given in the same dose as in Group A, and ACT was kept at the same level.
      Group C (n = 38) had the same coated ECC set as Group B, but intravenous heparin
      was reduced to 150 IU/kg, and during ECC, ACT was set to be > or =240 s. The same
      ECC components were used in all 3 groups including roller pumps, coronary
      suction, and an open cardiotomy reservoir. Thrombin generation as indicated by
      F1/F2 was significantly elevated at an ECC duration >60 min if heparin-coated ECC
      combined with low dose systemic heparinization was employed. Complexed thrombin
      (TAT) was significantly elevated after administration of protamine. Release of D
      dimers indicating fibrinolysis was not significantly different between groups.
      Signs of clinical thromboembolism, i.e., postoperative neurological deficit,
      occurred in 2 patients in Group A and 1 patient in Group C. We conclude that
      heparin-coated extracorporeal circulation combined with reduced systemic
      heparinization intraoperatively leads to significantly increased thrombin
      generation, but not to increased fibrinolysis.

PMID- 11453880
TI  - Relation between echinocytosis and erythrocyte calcium content in hemodialyzed
      uremic patients.
AB  - A rise in intracellular calcium concentration in erythrocytes has multiple
      effects on these cells. The purpose of this study was to determine the changes of
      calcium content in red blood cells (RBCs) and of echinocyte percentages in uremic
      patients during hemodialysis sessions. In 30 uremic patients under hemodialysis,
      the calcium content of RBCs and echinocyte percentages were determined in 3 blood
      samples collected at 0 min hemodialysis (prehemodialysis), 45 min hemodialysis,
      and 240 min hemodialysis (end hemodialysis) for a 4 h hemodialysis session.
      Calcium content of RBCs and echinocytes were also determined in 22 normal
      subjects (controls). The findings of the present study were that the mean values
      (+/-SD) of calcium content of RBCs in patients at 0 min hemodialysis, 45 min
      hemodialysis, and 240 min hemodialysis were 2.00 +/- 1.0, 2.66 +/- 0.87, and 1.62
      +/- 0.66 microg/ml respectively and 0.65 +/- 0.07 microg/ml in controls. These
      values show that the calcium content of RBCs in uremic patients at 0 min
      hemodialysis, 45 min hemodialysis, and 240 hemodialysis was significantly higher
      than in controls (p < 0.0001), and that RBC calcium content at 45 min
      hemodialysis was significantly higher in comparison to that at 0 min hemodialysis
      (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001), while that at 240
      min hemodialysis was significantly lower than at 0 min hemodialysis (p < 0.05).
      The mean values (+/-SD) of echinocyte percentages in patients at 0 min
      hemodialysis, 45 min hemodialysis, and 240 hemodialysis were 11.93 +/- 6.18,
      17.23 +/- 4.1, and 7.96 +/- 5.67% respectively, and in controls ranged from 0 to
      1%. The values in uremic patients show a transient increase of echinocyte
      percentages at 45 min hemodialysis, which is significant in comparison to that at
      0 min hemodialysis (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001).
      Echinocyte percentages at 240 min hemodialysis were significantly lower to those
      at 0 min hemodialysis (p < 0.001). Correlation between calcium content of
      erythrocytes and echinocyte percentages shows a significantly positive
      relationship at 45 min hemodialysis (r = 0.368, p < 0.05) but no significant
      relationship at 0 min hemodialysis and 240 min hemodialysis. In conclusion,
      uremic patients under hemodialysis present with high calcium content in
      erythrocytes and abnormal erythrocytes like echinocytes. A rapid and transient
      increase of erythrocyte calcium is also accompanied by transient elevation of
      echinocytes in the first hour of hemodialysis (45 min hemodialysis), which
      returns after hemodialysis to lower than prehemodialysis levels.

PMID- 11453881
TI  - Antibacterial effect of antibiotic solution on cellular viability in canine
      veins.
AB  - Pretreatment of tissue by using antibiotics is a critical step to prevent
      microbial contamination before venous transplantation. In this study, the optimal
      time and temperature of antibiotic solution treatment for maintaining cellular
      viability with antibacterial effect were investigated. The antibiotic-nutrient
      solutions were composed of cefoxitin, lincomycin, vancomycin, and polymyxin B in
      RPMI-1640 medium. After various antibiotic solution treatment times (4, 8, and 12
      h) and temperatures (4, 25, and 37 degrees C), the viabilities of cells
      dissociated from veins (jugular vein, femoral vein, superior vena cava, and
      inferior vena cava) were determined. Double staining by Griffonia simplicifolia
      agglutins-fluorescein isothiocyanate (GS1-FITC) and propidium iodide was used. To
      measure the antibacterial effect of the antibiotic solution, canine veins were
      artificially infected by 3 kinds of bacteria (Staphylococcus aureus, Escherichia
      coli, and Klebsiella pneumoniae) and were treated by antibiotic solutions as
      viability test conditions. After the treatment with the antibiotic solution, the
      tissue was minced, and the homogenized tissue fraction was cultured on standard
      method agar. The colony that seemed to be resistant to the antibiotic solution
      was counted. At 37 and 25 degrees C, the viability of whole cells decreased
      significantly Asymptotic Significance 2-tailed (Asymp.Sig 2-tailed) < 0.05 after
      4 h of antibiotic solution treatment, whereas at 4 degrees C it began to reduce
      significantly after 8 h of treatment. By antibiotic solution treatment at all 3
      temperatures for 4 h, no significant difference in viability of the endothelial
      cells and whole cells was observed. To maintain the donor vein's cellular
      viability until transplantation, antibiotic solution treatment for 4 h at 4
      degrees C is assumed to be appropriate.

PMID- 11453882
TI  - Development of a new hollow fiber silicone membrane oxygenator: in vitro study.
AB  - An experimental silicone hollow fiber membrane oxygenator for long-term
      extracorporeal membrane oxygenation (ECMO) was developed in our laboratory using
      an ultrathin silicone hollow fiber. However, the marginal gas transfer
      performances and a high-pressure drop in some cases were demonstrated in the
      initial models. In order to improve performance the following features were
      incorporated in the most recent oxygenator model: increasing the fiber length and
      total surface area, decreasing the packing density, and modifying the flow
      distributor. The aim of this study was to evaluate the gas transfer performances
      and biocompatibility of this newly improved model with in vitro experiments.
      According to the established method in our laboratory, in vitro studies were
      performed using fresh bovine blood. Gas transfer performance tests were performed
      at a blood flow rate of 0.5 to 6 L/min and a V/Q ratio (V = gas flow rate, Q =
      blood flow rate) of 2 and 3. Hemolysis tests were performed at a blood flow rate
      of 1 and 5 L/min. Blood pressure drop was also measured. At a blood flow rate of
      1 L/min and V/Q = 3, the O2 and CO2 gas transfer rates were 72.45 +/- 1.24 and
      39.87 +/- 2.92 ml/min, respectively. At a blood flow rate of 2 L/min and V/Q = 3,
      the O2 and CO2 gas transfer rates were 128.83 +/- 1.09 and 47.49 +/- 5.11 ml/min.
      Clearly, these data were superior to those obtained with previous models. As for
      the pressure drop and hemolytic performance, remarkable improvements were also
      demonstrated. These data indicate that this newly improved oxygenator is superior
      to the previous model and may be clinically acceptable for long-term ECMO
      application.

PMID- 11453883
TI  - Gas transfer performance of a hollow fiber silicone membrane oxygenator: ex vivo
      study.
AB  - Based on the results of in vitro studies of many experimental models, a silicone
      hollow fiber membrane oxygenator for pediatric cardiopulmonary bypass (CPB) and
      extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin
      silicone hollow fiber with a 300 microm outer diameter and a wall thickness of 50
      microm. In this study, we evaluated the gas transfer performance of this
      oxygenator simulating pediatric CPB and ECMO conditions. Two ex vivo studies in a
      pediatric CPB condition for 6 h and 5 ex vivo studies in an ECMO condition for 1
      week were performed with venoarterial bypass using healthy calves. At a blood
      flow rate of 2 L/min and V/Q = 4 (V = gas flow rate, Q = blood flow rate)
      (pediatric CPB condition), the O2 and CO2 gas transfer rates were maintained at
      97.44 +/- 8.88 (mean +/- SD) and 43.59 +/- 15.75 ml/min/m2, respectively. At a
      blood flow rate of 1 L/min and V/Q = 4 (ECMO condition), the O2 and CO2 gas
      transfer rates were maintained at 56.15 +/- 8.49 and 42.47 +/- 9.22 ml/min/m2,
      respectively. These data suggest that this preclinical silicone membrane hollow
      fiber oxygenator may be acceptable for both pediatric CPB and long-term ECMO use.

PMID- 11453884
TI  - Learning from previous responses in phase I dose-escalation studies.
AB  - Dose escalation in phase I studies is generally performed on the basis of
      clinical experience and judgement. In this paper some of the statistical
      approaches that have been proposed for the formalization of the procedure are
      described. Apart from the use of the Continual Reassessment Method in oncology
      studies, such formal methods have received little implementation. The purpose of
      presenting them here is to promote their further exploration and appropriate
      implementation. Certain limitations are discussed, which will be best overcome by
      collaboration between clinical pharmacologists and statisticians.

PMID- 11453885
TI  - Continuing Medical Education in Clinical Pharmacology and Therapeutics: report of
      a questionnaire survey.
AB  - AIMS: To seek the views of medically qualified members of the Clinical Section of
      the British Pharmacological Society (BPS) on their perceived needs for Continuing
      Medical Education (CME); on how and by whom these needs should be addressed; and
      on how the outcome of any educational intervention might best be assessed.
      METHODS: A structured questionnaire. RESULTS: Of 233 recipients, 140 (60%)
      responded, but only 123 of these fulfilled the criteria for analysis. A large
      majority of respondents were clinicians, most of whom devoted at least 25% of
      their working week to their NHS commitment. There was widespread reliance on
      textbooks and journals as sources of CME, supplemented by discussions with
      specialist peers at national and international meetings. Many felt that
      fulfilling even this agenda was stretching their commitment to the limit, and
      their greatest need was for protected time in which to learn. There was a desire
      among 49% of all respondents for the BPS Clinical Section to take some
      responsibilty for addressing the future needs of its members, and 75% took the
      view that academic departments should contribute to the development and updating
      of materials. There was no clear agreement about what these should comprise, but
      around half of all respondents favoured web-based, journal-based or computer
      assisted educational material offering self-assessment opportunities; and CME
      symposia or workshops at BPS meetings. Almost half (46%) felt that assessment of
      CME should be integrated with a well-organized appraisal system and the use of
      portfolios. Six out of 10 respondents were already, or were about to be,
      regularly appraised at their place of work. CONCLUSIONS: The questionnaire survey
      revealed a broad canvas of views and little evidence of consensus except for a
      general plea for more time in which to learn. The aim of the Clinical Section
      should be to facilitate and help its members to organize their learning, in a way
      that is consistent with national trends in Continuing Professional Development.
      The Clinical Section should co-ordinate the setting up of an electronic library
      of appropriate published material, compiled by academic and industrial sources,
      that would guide members seeking up-to-date knowledge of Clinical Pharmacology
      and Therapeutics. The British Journal of Clinical Pharmacology (BJCP) should
      commission review articles on recent developments where no suitable published
      material exists. Academic departments should also be invited to identify or
      develop self-assessment material that members could use to reinforce their
      learning, and demonstrate their knowledge to relevant professional bodies. The
      Clinical Section should organize Symposia and Workshops at which contentious
      issues in Clinical Pharmacology and Therapeutics can be discussed and resolved.

PMID- 11453886
TI  - Seasonal differences in finger skin temperature and microvascular blood flow in
      healthy men and women are exaggerated in women with primary Raynaud's phenomenon.
AB  - AIMS: Patients with primary Raynaud's phenomenon (PRP) have more severe symptoms
      in the winter. The aetiology of this is more complex than simply increased
      vasoconstriction in response to the immediate ambient temperature. The aim of
      this study was to investigate differences in skin temperature (Tsk),
      microvascular blood flow and responses to endothelium-dependent and independent
      vasodilators in healthy controls, and women with PRP under identical
      environmental temperatures but in different seasons. METHODS: Ten women with PRP
      were compared with age matched women (10) and men (10). Finger skin responses
      were recorded immediately on arrival, after stabilizing in a temperature
      regulated laboratory at 22-24 degrees C, and at matched warm (35 degrees C) and
      cold (15 degrees C) Tsk in the winter and summer. Baseline red blood cell flux
      (r.b.c. flux), and the change in flux in response to iontophoresis of
      acetylcholine (ACh) and sodium nitroprusside (SNP) were recorded by laser Doppler
      fluxmetry at the warm and cold Tsk. RESULTS: Arrival Tsk were significantly
      cooler for all subjects during the winter (mean seasonal difference -2.6 degrees
      C, P < 0.0001), and markedly colder in subjects with PRP (mean seasonal
      difference -3.5 degrees C, P < 0.0005). Statistically significant seasonal
      differences persisted in all subjects at stable Tsk despite an identical
      laboratory temperature (mean difference 1.3 degrees C, P < 0.0001). To achieve
      comparable controlled finger Tsk a significantly colder local environment was
      required for male controls (mean of -2.1 degrees C, P < 0.0001), and a
      significantly warmer environment for subjects with PRP (mean of + 2.4 degrees C,
      P < 0.0001) compared with female controls. This needed to be warmer in the
      winter, by a mean of 2.4 degrees C, than the summer for all subjects.
      Vasodilatation in response to ACh, but not SNP, was significantly smaller (P <
      0.0001) in the PRP group compared with the female controls for all visits, with
      most of this difference arising in the winter visits (P < 0.01). CONCLUSIONS:
      There is a seasonal and persistent influence on finger Tsk, and microvascular
      blood flow in healthy men and women, which modifies the observed responses to
      immediate changes in finger Tsk. The seasonal differences are greater in women
      than men, and are further exaggerated in women with PRP, in whom this is
      associated with reduced endothelium-dependent vasodilatation.

PMID- 11453887
TI  - Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic
      effects in healthy volunteers and in congestive heart failure patients.
AB  - AIMS: We compared the relationships between the plasma concentrations (C) of
      perindoprilat, active metabolite of the angiotensin I-converting enzyme inhibitor
      (ACEI) perindopril, and the effects (E) induced on plasma converting enzyme
      activity (PCEA) and brachial vascular resistance (BVR) in healthy volunteers (HV)
      and in congestive heart failure (CHF) patients after single oral doses of
      perindopril. METHODS: Six HV received three doses of perindopril (4, 8, 16 mg) in
      a placebo-controlled, randomized, double-blind, crossover study whereas 10 CHF
      patients received one dose (4 mg) in an open study. Each variable was determined
      before and 6-12 times after drug intake. E (% variations from baseline) were
      individually related to C (ng ml(-1)) by the Hill model E=Emax x
      Cgamma/(CE50gamma + Cgamma). When data showed a hysteresis loop, an effect
      compartment was used. RESULTS: (means+/-s.d.) In HV, relationships between C and
      E were direct whereas in CHF patients, they showed hysteresis loops with optimal
      k(e0) values of 0.13 +/- 0.16 and 0.13 +/- 0.07 h(-1) for PCEA and BVR,
      respectively. For PCEA, with Emax set to -100%, CE50 = 1.87 +/- 0.60 and 1.36 +/-
      1.33 ng ml(-1) (P = 0.34) and gamma = 0.90 +/- 0.13 and 1.11 +/- 0.47 (P = 0.23)
      in HV and CHF patients, respectively. For BVR, Emax= -41 +/- 14% and -60 +/- 7%
      (P = 0.02), CE50 = 4.95 +/- 2.62 and 1.38 +/- 0.85 ng ml(-1) (P = 0.02), and
      gamma = 2.25 +/- 1.54 and 3.06 +/- 1.37 (P = 0.32) in HV and CHF patients,
      respectively. CONCLUSIONS: Whereas concentration-effect relationships were
      similar in HV and CHF patients for PCEA blockade, they strongly differed for
      regional haemodynamics. This result probably expresses the different
      involvements, in HV and CHF patients, of angiotensinergic and nonangiotensinergic
      mechanisms in the haemodynamic effects of ACEIs.

PMID- 11453888
TI  - Contribution of dihydrocodeine and dihydromorphine to analgesia following
      dihydrocodeine administration in man: a PK-PD modelling analysis.
AB  - AIMS: It is not clear whether the analgesic effect following dihydrocodeine (DHC)
      administration is due to either DHC itself or its metabolite, dihydromorphine
      (DHM). We examined the relative contribution of DHC and DHM to analgesia
      following DHC administration in a group of healthy volunteers using a PK-PD link
      modelling approach. METHODS: A single oral dose of DHC (90 mg) was administered
      to 10 healthy volunteers in a randomised, double-blind, placebo-controlled study.
      A computerized cold pressor test (CPT) was used to measure analgesia. On each
      study day, the volunteers performed the CPT before study medication and at 1.25,
      2.75, 4.25 and 5.75 h postdose. Blood samples were taken at 0.25 h (predose) and
      then at half hourly intervals for 5.75 h postdose. PK-PD link modelling was used
      to describe the relationships between DHC, DHM and analgesic effect. RESULTS:
      Mean pain AUCs following DHC administration were significantly different to those
      following placebo administration (P = 0.001). Mean pain AUC changes were 91 score
      x s(-1) for DHC and -17 score x s(-1) for placebo (95% CI = +/- 36.5 for both
      treatments). The assumption of a simple linear relationship between DHC
      concentration and effect provided a significantly better fit than the model
      containing DHM as the active moiety (AIC = 4.431 vs 4.668, respectively). The
      more complex models did not improve the likelihood of model fits significantly.
      CONCLUSIONS: The findings suggest that the analgesic effect following DHC
      ingestion is mainly attributed to the parent drug rather than its DHM metabolite.
      It can thus be inferred that polymorphic differences in DHC metabolism to DHM
      have little or no effect on the analgesic affect.

PMID- 11453889
TI  - Dihydroergotamine: discrepancy between arterial, arteriolar and pharmacokinetic
      data.
AB  - AIMS: To investigate the peripheral vascular effects and pharmacokinetics of
      dihydroergotamine (DHE) 0.5 mg after a single subcutaneous administration in
      humans. METHODS: A double-blind, placebo-controlled cross-over study was
      performed in 10 healthy male subjects. A wash-out period of 2 weeks separated the
      two study periods. During each period, just before and at regular intervals after
      drug administration, vascular measurements were performed and venous blood
      samples were drawn. Vessel wall properties were assessed at the brachial artery,
      by ultrasound and applanation tonometry. Blood pressure and heart rate were
      recorded with an oscillometric device. Forearm blood flow was measured with
      venous occlusion plethysmography. For all parameter-time curves the area under
      the curve (AUC) was calculated. Differences in AUC after placebo and DHE
      (DeltaAUC) were analysed and the time-course of the difference assessed. DHE
      pharmacokinetics were analysed according to a two-compartment open model with an
      absorption phase. RESULTS: AUC for blood pressure, heart rate and forearm
      vascular resistance did not change after DHE. Brachial artery diameter and
      compliance decreased (P < 0.01); DeltaAUC (95% confidence interval) equalled 
      8.81 mm h (-12.97/-4.65) and -0.98 mm2 kPa(-1) h (-1.61/-0.34), respectively.
      Diameter decreased (P < 0.05) from 1 until 24 h after DHE (peak decrease 9.7% at
      10 h); compliance from 2 until 32 h (24.8% at 2 h). Time to reach maximum plasma
      concentration of DHE averaged 0.33 +/- 0.08 h (+/- s.e.mean); terminal half-life
      was 5.63 +/- 1.15 h. CONCLUSIONS: DHE decreased diameter and compliance of the
      brachial artery whereas forearm vascular resistance remained unchanged. Thus, DHE
      acts on conduit arteries without affecting resistance arteries. Furthermore, a
      discrepancy was demonstrated between the plasma concentrations of DHE which
      rapidly reach peak levels and quickly decline, and its long lasting
      vasoconstrictor activity.

PMID- 11453890
TI  - In vitro metabolism and drug interaction potential of a new highly potent anti
      cytomegalovirus molecule, CMV423 (2-chloro 3-pyridine 3-yl 5,6,7,8
      tetrahydroindolizine I-carboxamide).
AB  - AIMS: To identify the enzymes involved in the metabolism of CMV423, a new
      anticytomegalovirus molecule, to evaluate its in vitro clearance and to
      investigate its potential involvement in drug/drug interactions that might occur
      in the clinic. METHODS: The enzymes involved in and the kinetics of CMV423
      biotransformation were determined using pools of human liver subcellular
      fractions and heterologously expressed human cytochromes P450 (CYP) and FMO. The
      effect of CMV423 on CYP probe activities as well as on indinavir and AZT
      metabolism was determined, and 26 drugs were tested for their potential to
      inhibit or activate CMV423 metabolism. RESULTS: CMV423 was oxidized by CYP and
      not by FMO or cytosolic enzymes. The Km values for 8-hydroxylation to rac-RPR
      127025, an active metabolite, and subsequent ketone formation by human liver
      microsomes were 44 +/- 13 microM and 47 +/- 11 microM, respectively, with
      corresponding Vmax/Km ratios of 14 and 4 microl min(-1) nmol(-1) P450. Inhibition
      with selective CYP inhibitors indicated that CYP1A2 was the main isoform
      involved, with some participation from CYP3A. Expressed human CYP1A1, 1A2, 2C9,
      3A4 and 2C8 catalysed rac-RPR 127025 formation with Km values of < 10 microM, 50
      +/- 21 microM, 55 +/- 19 microM, circa 282 +/- 61 microM and circa 1450 microM,
      respectively. CYP1B1, 2A6, 2B6, 2C19, 2D6, 2E1 or 3A5 did not catalyse the
      reaction to any detectable extent. CYP1A1 and 3A4 also catalysed ketone formation
      from rac-RPR 127025. In human liver microsomes, CMV423 at 1 and 10 microM
      inhibited CYP1A2 activity up to 31% and 63%, respectively, CYP3A4 activity up to
      40% (10 microM) and CYP2C9 activity by 35% (1 and 10 microM). No effect was
      observed on CYP2A6, 2D6 and 2E1 activities. CMV423 had no effect on indinavir and
      AZT metabolism. Amongst 26 drugs tested, none inhibited CMV423 metabolism in
      vitro at therapeutic concentrations. CONCLUSIONS: CMV423 is mainly metabolized by
      CYP1A2 and 3A4. Its metabolism should not be saturable at the targeted
      therapeutic concentrations range (Cmax < 1 microM). CMV423 will probably affect
      CYP1A2 and 1A1 activities in vivo to some extent, but no other drug-drug
      interactions are expected.

PMID- 11453891
TI  - Diurnal variation in the biliary excretion of flomoxef in patients with
      percutaneous transhepatic biliary drainage.
AB  - AIMS: To examine diurnal variation in biliary excretion of flomoxef. METHODS:
      Flomoxef (1 g) was injected intravenously in eight patients with percutaneous
      transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over
      design with a 36 h washout period. Drained biliary fluid was collected for 6 h
      after each dosing. These patients still had mild to moderate hepatic dysfunction.
      RESULTS: Bile flow and bile acid excretion for 6 h after dosing did not differ
      significantly between the 09.00 h and 21.00 h treatments. The maximum
      concentration of biliary flomoxef was significantly greater and its total
      excretion for 6 h tended to be greater after the 21.00 h dose [maximum
      concentration (microg ml(-1)): 34.2 +/- 29.9 (09.00 h dose) vs 43.5 +/- 28.3
      (21.00 h dose) (95% confidence interval for difference: 2.6 approximately 15.9, P
      = 0.013); total excretion (mg 6 h(-1)): 1.4 +/- 1.3 (09.00 h dose) vs 1.6 +/- 1.2
      (21.00 h dose) (95% confidence interval for difference: -26.8, 313.7, P =
      0.087)]. The period that biliary flomoxef remained above the minimal inhibitory
      concentration did not differ significantly between the two treatment times.
      CONCLUSIONS: These results suggest that biliary excretion of flomoxef shows
      diurnal variation. However, as the difference was relatively small, flomoxef
      could be given at any time of day without any dosage adjustments.

PMID- 11453892
TI  - Influence of beta-adrenoceptor antagonists on the pharmacokinetics of
      rizatriptan, a 5-HT1B/1D agonist: differential effects of propranolol, nadolol
      and metoprolol.
AB  - AIMS: Patients with migraine may receive the 5-HT1B/1D agonist, rizatriptan (5 or
      10 mg), to control acute attacks. Patients with frequent attacks may also receive
      propranolol or other beta-adrenoceptor antagonists for migraine prophylaxis. The
      present studies investigated the potential for pharmacokinetic or pharmacodynamic
      interaction between beta-adrenoceptor blockers and rizatriptan. METHODS: Four
      double-blind, placebo-controlled, randomized crossover investigations were
      performed in a total of 51 healthy subjects. A single 10 mg dose of rizatriptan
      was administered after 7 days' administration of propranolol (60 and 120 mg twice
      daily), nadolol (80 mg twice daily), metoprolol (100 mg twice daily) or placebo.
      Rizatriptan pharmacokinetics were assessed. In vitro incubations of rizatriptan
      and sumatriptan with various beta-adrenoceptor blockers were performed in human
      S9 fraction. Production of the indole-acetic acid-MAO-A metabolite of each
      triptan was measured. RESULTS: Administration of rizatriptan during propranolol
      treatment (120 mg twice daily for 7.5 days) increased the AUC(0, infinity) for
      rizatriptan by approximately 67% and the Cmax by approximately 75%. A reduction
      in the dose of propranolol (60 mg twice daily) and/or the incorporation of a
      delay (1 or 2 h) between propranolol and rizatriptan administration did not
      produce a statistically significant change in the effect of propranolol on
      rizatriptan pharmacokinetics. Administration of rizatriptan together with nadolol
      (80 mg twice daily) or metoprolol (100 mg twice daily) for 7 days did not
      significantly alter the pharmacokinetics of rizatriptan. No untoward adverse
      experiences attributable to the pharmacokinetic interaction between propranolol
      and rizatriptan were observed, and no subjects developed serious clinical,
      laboratory, or other significant adverse experiences during coadministration of
      rizatriptan with any of the beta-adrenoceptor blockers. In vitro incubations
      showed that propranolol, but not other beta-adrenoceptor blockers significantly
      inhibited the production of the indole-acetic acid metabolite of rizatriptan and
      sumatriptan. CONCLUSIONS: These results suggest that propranolol increases plasma
      concentrations of rizatriptan by inhibiting monoamine oxidase-A. When prescribing
      rizatriptan to migraine patients receiving propranolol for prophylaxis, the 5 mg
      dose of rizatriptan is recommended. Administration with other beta-adrenoceptor
      blockers does not require consideration of a dose adjustment.

PMID- 11453893
TI  - Incidence of adverse drug reactions in paediatric in/out-patients: a systematic
      review and meta-analysis of prospective studies.
AB  - AIMS: To explore the usefulness of data derived from observational studies on
      adverse drug reactions (ADRs) in defining and preventing the risk of
      pharmacological interventions in children in different health care settings.
      METHODS: A systematic review of studies on ADRs in hospitalized children, in
      outpatient children, and on ADRs causing paediatric hospital admissions was
      performed. Studies were identified through a search of the MEDLINE and EMBASE
      databases. The inclusion criteria required that the population was not selected
      for particular conditions or drug exposure and prospective monitoring was used
      for identifying ADRs. Data were analysed by a random-effects model. RESULTS:
      Seventeen prospective studies were included. In hospitalized children, the
      overall incidence of ADRs was 9.53% (95% confidence interval [CI], 6.81, 12.26);
      severe reactions accounted for 12.29% (95%CI, 8.43,16.17) of the total. The
      overall rate of paediatric hospital admissions due to ADRs was 2.09% (95%CI,
      1.02, 3.77); 39.3% (95%CI, 30.7,47.9) of the ADRs causing hospital admissions
      were life threatening reactions. For outpatient children the overall incidence of
      ADRs was 1.46% (95%CI, 0.7, 3.03). CONCLUSIONS: The results show that ADRs in
      children are a significant public health issue. The completeness and accuracy of
      prescription reporting as well as clinical information from studies was a rarity,
      making it difficult for health practitioners to implement evidence based
      preventive strategies. Further, methodologically sound drug surveillance studies
      are necessary for an effective promotion of a safer use of drugs in children.

PMID- 11453894
TI  - Nature, frequency and determinants of prescription modifications in Dutch
      community pharmacies.
AB  - AIMS: To examine the nature, frequency and determinants of prescription
      modifications in Dutch community pharmacies. METHODS: A prospective case-control
      study comparing modified prescriptions with nonmodified prescriptions was carried
      out in 141 Dutch community pharmacies. 2014 modified prescriptions (cases),
      collected in the selected pharmacies on a predetermined day in a specific period
      (25th February until 12th March 1999) and 2581 nonmodified prescriptions
      (controls) randomly selected on the same day were studied. The nature and
      frequency of prescription modifications and patient, drug and prescriber related
      determinants for a modified prescription were assessed. RESULTS: The overall
      incidence of prescription modifications was 4.3%, with a mean of 14.3
      modifications per pharmacy per day. For prescription only medicines (POM) the
      incidence was 4.9%. The majority of POM modifications concerned a clarification
      (71.8%). In 22.2% a prescription could potentially have had clinical consequences
      when not altered; in more than half of the latter it concerned a dose error
      (13.7% of all cases). POM prescriptions of patients of 40-65 years had a
      significantly lower chance of modification compared with those of younger people
      (OR = 0.74 [0.64-0.86]). With respect to medication-class, we found a higher
      chance of POM modifications in the respiratory domain (OR = 1.48 [1.23-1.79]) and
      a decreased chance for nervous system POMs (OR = 0.71 [0.61-0.83]). With regard
      to prescriber-related determinants modifications were found three times more
      often in non printed prescriptions than in printed ones (OR = 3.30 [2.90-3.75]).
      Compared with prescriptions by the patient's own GP, prescriptions of specialists
      (OR = 1.82 [1.57-2.11]), other GP's (OR = 1.49 [1.02-2.17]) and other prescribers
      such as dentists and midwives (OR = 1.95 [1.06-3.57]) gave a higher probability
      of prescription modifications. When a GP had no on-line access to the computer of
      the pharmacy the chance of a modification was also higher (OR = 1.61 [1.33
      1.94]). Multivariate analysis revealed that a nonprinted prescription was the
      strongest independent determinant of prescription modifications (OR = 3.32 [2.87
      3.84]), remaining so after adjustment for GP computer link to the pharmacy and
      for type of prescriber. CONCLUSIONS: At least 30% of Dutch community pharmacies
      corrected 2.8 POM prescriptions per pharmacy per working day, which could
      potentially have had clinical consequences if not altered. If the study sample is
      representative for The Netherlands, Dutch community pharmacies correct a total of
      approximately 4400 of these prescriptions per working day. Using computerized
      systems to generate prescriptions is an important strategy to reduce the
      incidence of prescription errors.

PMID- 11453895
TI  - Dose-response for adrenal suppression with hydrofluoroalkane formulations of
      fluticasone propionate and beclomethasone dipropionate.
AB  - AIMS: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is
      important to know the relative systemic safety profiles of inhaled
      corticosteroids. We therefore decided to compare systemic bioavailability of HFA
      beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). METHODS:
      Sixteen healthy volunteers were randomised in placebo-controlled single blind
      cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week
      cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 microg day(
      1), with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and
      early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum
      cortisol were measured after each placebo and dosing period. All data were log
      transformed to normalize their distribution. RESULTS: Urine and serum cortisol
      were suppressed by 2000 microg FP and BDP vs placebo and by 1000 microg BDP vs
      placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary
      cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000
      microg BDP vs 1000 microg FP (P < 0.05), amounting to a geometric mean fold
      difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low
      values less than 3 nmol mmol(-1) with BDP than FP at 1000 microg: n = 8/16 vs n =
      2/16 (P < 0.05). CONCLUSIONS: There was dose-related suppression of corrected
      urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression
      of overnight urinary cortisol/creatinine ratio was significantly greater with HFA
      BDP than HFA-FP at 1000 microg. This suggests that the greater glucocorticoid
      potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.

PMID- 11453896
TI  - Effect of the CYP2C19 oxidation polymorphism on fluoxetine metabolism in Chinese
      healthy subjects.
AB  - AIMS: The study was designed to investigate whether genetically determined
      CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects.
      METHODS: A single oral dose of fluoxetine (40 mg) was administrated successively
      to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor
      metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5-7 half
      lives and fluoxetine, and norfluoxetine were determined by reversed-phase high
      performance liquid chromatography. RESULTS: Poor metabolizers (PMs) showed a mean
      46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128%
      increase in area under the concentration vs time curve (AUC(0, infinity), P <
      0.001), 113% increase in terminal elimination half-life (t(1/2)) (P < 0.001), and
      55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean
      +/- (s.d) norfluoxetine AUC(0, 192 h) was significantly lower in PMs than that in
      EMs (1343 +/- 277 vs 2935 +/- 311, P < 0.001). Mean fluoxetine Cmax and AUC(0,
      infinity) in wild-type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower
      than that in PMs (22.4 +/- 3.9 vs 36.7 +/- 8.9, P < 0.001; 732 +/- 42 vs 2152 +/-
      492, P < 0.001, respectively). Mean oral clearance in individuals with the wild
      type homozygous genotype was significantly higher than that in heterozygotes and
      that in PMs (54.7 +/- 3.4 vs 36.0 +/- 8.7, P < 0.01; 54.7 +/- 3.4 vs 20.6 +/-
      6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0, 192 h) in PMs was
      significantly lower than that in wild type homozygotes (1343 +/- 277 vs 3163 +/-
      121, P < 0.05) and that in heterozygotes (1343 +/- 277 vs 2706 +/- 273, P <
      0.001), respectively. CONCLUSIONS: The results indicated that CYP2C19 appears to
      play a major role in the metabolism of fluoxetine, and in particular its N
      demethylation among Chinese healthy subjects.

PMID- 11453897
TI  - Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver
      microsomes.
AB  - AIMS: To study the influence of CYP2D6*10 on the formation of p-hydroxymexiletine
      (PHM) and hydroxymethylmexiletine (HMM) using microsomes from human liver of
      known genotypes. METHODS: Microsomes from human livers of genotype CYP2D6*1/*1 (n
      = 5), *1/*10 (n = 6) and *10/*10 (n = 6) were used in this study. The formation
      of PHM and HMM was determined by high-performance liquid chromatography. RESULTS:
      The formation rates of PHM and HMM were decreased by more than 50% and 85% in
      CYP2D6*1/*10 and *10/*10 microsomes, respectively, compared with *1/*1
      microsomes. CONCLUSIONS: The metabolism of mexiletine to form PHM and HMM appears
      to be impaired to a significant extent in human liver microsomes from hetero- and
      homozygotes of CYP2D6*10.

PMID- 11453898
TI  - Optimizing drug development: strategies to assess drug metabolism/transporter
      interaction potential--towards a consensus.

PMID- 11453899
TI  - Treating basal cell carcinoma: has photodynamic therapy come of age?

PMID- 11453900
TI  - Topically applied lactic acid increases spontaneous secretion of vascular
      endothelial growth factor by human reconstructed epidermis.
AB  - BACKGROUND: Alpha-hydroxy acids (AHAs) are widely used for the treatment of
      hyperkeratotic skin disorders and photodamaged skin. OBJECTIVES: To investigate
      the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes
      (KCs) of human reconstructed epidermis. METHODS: Creams containing 1.5%, 3% or 5%
      LA or vehicle controls were topically applied on to human epidermal equivalents
      (EEs). After 24 h, EEs were analysed for morphology and for the presence of
      apoptotic cells. Secretion of vascular endothelial growth factor (VEGF),
      angiogenin (ANG) and interleukin (IL)-8 was measured in the supernatants by
      enzyme-linked immunosorbent assay. RESULTS: LA led to a concentration-dependent
      increase in apoptotic cells as determined by cell morphology and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling. VEGF secretion was increased 2.5- and 2.8-fold (P < 0.05) over vehicle
      control after treatment with 1.5% and 3% LA, respectively. No significant
      increase in VEGF secretion was detected with 5% LA. In contrast to VEGF,
      secretion of ANG was decreased by LA in a concentration-dependent manner (0.5
      fold for 5% LA; P < 0.01). No significant changes in IL-8 secretion were found
      with any of the concentrations tested. CONCLUSIONS: Our data demonstrate that the
      topical application of AHAs modulates the secretion of cytokines by KCs.
      Regulation of KC-derived growth factors and cytokines by AHAs might represent a
      mechanism contributing to their therapeutic effects in disorders such as
      photoageing.

PMID- 11453901
TI  - Glycation during human dermal intrinsic and actinic ageing: an in vivo and in
      vitro model study.
AB  - BACKGROUND: Non-enzymatic glycation occurring in normal human skin plays an
      important part in ageing. OBJECTIVES To visualize and quantify, in human
      subjects, the extent of glycation during human dermal intrinsic and actinic
      ageing, and to develop a reliable reproducible in vitro model for evaluating the
      efficacy of potential inhibitors of glycation. METHODS: By immunohistochemistry
      using a monoclonal antibody recognizing carboxymethyl lysine, an advanced
      glycation end-product (AGE) (first objective), and by incubating dead de
      epidermized dermis (DED) with glucose to simulate ageing-induced glycation in a
      human dermal equivalent model (second objective). RESULTS: We found that
      glycation of the dermis generally arises after 35 years, then increases rapidly
      with intrinsic ageing. We also noticed an enhancement of glycation by solar
      irradiation that occurred via glycation of the elastic fibre network or solar
      elastosis tissue. In the model, production of AGEs appeared in a time-dependent
      way, mimicking glycation observed in vivo during chronological ageing.
      Irradiation of DED before incubation with glucose strongly enhanced induction of
      AGEs, corresponding to the effect of solar irradiation on AGEs observed in vivo.
      CONCLUSIONS: These results confirm a marked increase of AGEs during intrinsic
      ageing in normal human skin and also suggest that glycation is enhanced in
      photoaged skin.

PMID- 11453902
TI  - Lipid analysis of follicular casts from cyanoacrylate strips as a new method for
      studying therapeutic effects of antiacne agents.
AB  - BACKGROUND: The cyanoacrylate follicular biopsy is an established method for the
      examination of the horny layer and quantitative assessment of microcomedones. We
      have optimized the method by separating follicular casts mechanically from the
      cyanoacrylate strips. OBJECTIVES: To use this method to analyse topical therapy
      induced changes of the lipid composition in the sebaceous follicular
      infundibulum. METHODS: Both the follicular casts and the residual skin surface
      strip, the last representing a mixture of stratum corneum and surface lipids,
      were extracted twice with n-hexane-ethanol under ultrasonication, evaporated,
      redissolved in chloroform-methanol and separated by high-performance thin layer
      chromatography, using cholesterol sulphate, cerebroside, ceramide types 3 and 4,
      cholesterol, oleic acid, triolein, cholesterol oleate and squalene as standards.
      Identification was performed by computer-assisted densitometric analysis. Six
      patient groups receiving adapalene 0.1%, tretinoin 0.025%, clindamycin 1%,
      clindamycin 1% + tretinoin 0.025%, benzoyl peroxide 5% or benzoyl peroxide 5% +
      erythromycin 2% were investigated before and 12 weeks after application. RESULTS:
      A significant decrease in free fatty acid proportions combined with an increase
      in triglycerides was observed in the groups receiving antimicrobial therapy,
      supporting the hypothesis of lipolysis due to microbial colonization. The groups
      treated with topical retinoids showed an additional significant increase in
      ceramide subfractions, most probably reflecting their influence on epidermal
      keratinization. CONCLUSIONS: Our method proved suitable for the detection of
      quantitative and qualitative changes in lipid profiles of both infundibulum cast
      content and surface lipids. It enabled simple, non-invasive and objective
      assessment of the most relevant lipid classes in the sebaceous infundibulum, and
      efficient monitoring of drug effects on the follicular infundibulum.

PMID- 11453903
TI  - A retrospective analysis of contact allergy to lanolin.
AB  - BACKGROUND: Lanolin is often stated to be an important sensitizer but some of the
      available literature is based on the analysis of high-risk patients. OBJECTIVES:
      To analyse the frequency of contact allergy to lanolin (wool alcohols) in a
      central London teaching hospital patch-test population. METHODS: Review of 24,449
      patients recorded on our database during 1982--96 who were tested with a standard
      series containing 30% wool alcohols. RESULTS: The mean annual rate of sensitivity
      to this allergen was 1.7%. The wool alcohols-allergic group contained a higher
      proportion of females (P < 0.05), and the mean age of both males and females
      (48.4 and 49.2 years) was higher than that of non-wool alcohols-allergic patients
      (41.4 and 35.9 years; P < 0.0005). There was no difference in atopic eczema
      status between these groups. The highest prevalence of allergy to wool alcohols
      was among patients with lower leg dermatitis (6.0%; 95% confidence interval, CI
      4.46--7.54), followed by those with anogenital dermatitis (3.23%; 95% CI 1.81-
      4.65). There was an unexplained decline in the rate of positive patch tests to
      Amerchol L-101. However, some patients who reacted to this were negative with
      wool alcohols, so it may be a useful additional test reagent. The mean rates of
      allergy to Eucerin (0.65% per annum) and 50% hydrogenated lanolin in petrolatum
      (1% per annum) were low, and we no longer use these as test reagents.
      CONCLUSIONS: This study illustrates that lanolin sensitization has remained at a
      relatively low and constant rate even in a high-risk population (i.e. patients
      with recent or active eczema).

PMID- 11453904
TI  - Protective gloves in Swedish dentistry: use and side-effects.
AB  - BACKGROUND: During the 1980s routine wearing of gloves in dentistry was
      recommended by health authorities in several countries. However, prolonged glove
      use is associated with side-effects of irritant and allergic origin. OBJECTIVES:
      To investigate the extent of glove use and self-reported glove intolerance
      reactions among Swedish dentists, and to examine how far IgE-mediated allergy to
      natural rubber latex (NRL) occurs in subjects who report rapid itching when in
      contact with protective gloves. SUBJECTS/METHODS: A postal questionnaire was
      answered by 3083 of 3500 licensed dentists, a response rate of 88%. Of the
      dentists who reported rapidly occurring itching of the hands from gloves, 131 of
      170 attended a clinical examination including a skin prick test (SPT) and a
      serological examination (RAST) for IgE-mediated allergy. RESULTS: Seventy-three
      per cent of the dentists reported daily glove use of more than 2 h, 48% more than
      6 h a day, and 6% reported no use. NRL gloves were used most frequently (P <
      0.001) and were the main material that elicited symptoms (P < 0.001). Female
      dentists reported more frequent glove use than males, as did young dentists (P <
      0.001) compared with older ones. Females also preferred vinyl gloves. Glove
      intolerance reactions were reported by 723 (23%) dentists, [females 28%, males
      21% (P < 0.001)] and were more common in younger dentists. Of the 417 dentists
      with reported hand eczema during the previous year, 54% reported glove
      intolerance, compared with 20% of the dentists without hand eczema (P < 0.001). A
      logistic regression analysis including hand eczema, age, sex and atopy showed
      that all these factors contributed significantly to the risk of glove
      intolerance, and that hand eczema was a stronger factor than atopy. In 15 of 131
      (11%) dentists examined for reported glove-related itch, latex allergy was
      verified by SPT and/or RAST. Glove-related conjunctivitis, rhinitis and asthma,
      in contrast to skin symptoms, showed a significant association with IgE-mediated
      allergy to NRL. CONCLUSIONS: Swedish dentists show good compliance with the
      recommendations for routine glove use. Intolerance reactions are frequently
      reported, especially by dentists with hand eczema, which emphasizes the need for
      preventive skin care programmes. Glove-related symptoms from mucous membranes
      showed a higher association with IgE-mediated allergy to NRL than reported
      itching of the skin, a fact that should be considered when composing screening
      questionnaires for NRL sensitization

PMID- 11453905
TI  - Repetitive usage testing with budesonide in experimental nickel--allergic contact
      dermatitis in individuals hypersensitive to budesonide.
AB  - BACKGROUND: Contact allergy to topical corticosteroids on patch testing is well
      recognized, but the clinical significance is uncertain. OBJECTIVES: To determine
      the clinical relevance of contact allergy to topical corticosteroids. METHODS:
      Seven patients hypersensitive to both budesonide and nickel repeatedly applied
      budesonide, betamethasone valerate or the common base for both corticosteroids to
      areas of experimentally induced nickel dermatitis. Nineteen controls allergic to
      nickel, but not budesonide went through the same procedure. RESULTS: Seventy-one
      per cent of the budesonide-allergic individuals experienced distant ipsilateral
      flares of toxicoderma-like eruptions, in addition to a severe deterioration of
      the experimental dermatitis treated with budesonide, i.e. increased erythema, and
      abundant papules and vesicles. The areas of dermatitis in all of the 19 controls
      healed uneventfully. CONCLUSIONS: The clinical relevance of a contact allergy to
      budesonide was thus substantiated.

PMID- 11453906
TI  - Immunohistochemical evaluation of psoriatic plaques following selective
      photothermolysis of the superficial capillaries.
AB  - BACKGROUND: Elongated and tortuous capillary loops are distinctive features of
      psoriasis. The significance of these microvascular changes in the pathogenesis of
      plaques, however, remains unclear. OBJECTIVES: To determine what part the
      expanded superficial capillary bed plays in the pathogenesis of clinical lesions
      by selectively thermolysing psoriatic capillaries with a pulsed dye laser (PDL).
      METHODS: Cutaneous lesions were biopsied before and after treatment and sections
      assessed by standard immunohistochemical techniques for changes in known
      indicators of angiogenesis, including endothelial surface area, endothelial cell
      proliferation and endothelial cell expression of adhesion molecules. We also
      measured lymphocytic infiltration and epidermal thickness, and quantified the
      presence of a marker of keratinocyte proliferation before and after treatment.
      RESULTS: The effect of the PDL was limited to the superficial capillary bed, with
      no changes in the microvessels (including venules and arterioles) of the upper
      reticular dermis. Although there was significant clinical improvement in plaques
      after treatment (P = 0.02), complete clearance of lesions was not achieved.
      Thermolysis of psoriatic capillaries caused a reduction in both endothelial
      surface area (P < 0.01) and endothelial cell proliferation in the superficial
      dermis (P = 0.04). Endothelial expression of surface adhesion molecules
      (integrins and E-selectin) important in angiogenesis was not, however, altered by
      treatment. The CD4+ and CD8+ T-cell infiltrate was significantly reduced in the
      superficial papillary dermis (P = 0.02 and P = 0.04, respectively), but not in
      the epidermis or upper reticular dermis. Laser treatment significantly reduced
      epidermal thickness (P = 0.001), but did not alter epidermal keratinocyte
      proliferation (P = 0.2). CONCLUSIONS: The results demonstrate that dermal
      capillary changes alone are unlikely to be causal in psoriasis. They indicate
      that the expanded psoriatic capillaries may be important in facilitating the
      access of activated T cells to the skin and in maintaining the psoriatic plaque.
      These results do not refute the consensus view that plaque formation may be
      mediated by the release of growth factors/cytokines from activated epidermal T
      cells/keratinocytes.

PMID- 11453907
TI  - Contrasting effects of an ultraviolet B and an ultraviolet A tanning lamp on
      interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1
      expression.
AB  - BACKGROUND: Recent studies have demonstrated that a tanning lamp emitting
      predominantly ultraviolet (UV) A induces significant yields of the type of
      potentially mutagenic DNA damage that are associated with the onset of skin
      cancer (i.e. cyclobutane pyrimidine dimers). UV-induced immunosuppression is also
      an important event leading to skin cancer. OBJECTIVES: To the modulation of key
      immunological molecules following exposure to a broad-spectrum UVB lamp and a
      predominantly UVA-emitting tanning lamp using model in vitro systems. METHODS: We
      compared secretion and mRNA expression of interleukin (IL)-6 and tumour necrosis
      factor (TNF)-alpha in normal human epidermal keratinocytes, and interferon (IFN)
      gamma-induced intracellular adhesion molecule (ICAM)-1 in normal human
      fibroblasts irradiated in vitro with a broad-spectrum UVB lamp or with a Philips
      'Performance' tanning lamp. RESULTS: With broad-spectrum UVB irradiation,
      upregulation of IL-6 and TNF-alpha mRNA was detected 6 h after irradiation, and a
      dose-dependent increase of cytokines in the supernatants of irradiated cells was
      found 24 h after irradiation. In contrast, there was no cytokine secretion and
      little evidence for mRNA upregulation following exposure to a tanning lamp. When
      cells were exposed first to broad-spectrum UVB, then the tanning lamp, UVB
      induced cytokine secretion was inhibited, although mRNA levels were upregulated
      to a level close to that observed with UVB alone. By using a Schott WG 320 nm
      filter to attenuate the level of UVB relative to UVA emitted by the tanning lamp,
      the inhibition of cytokine secretion was shown to be associated with UVA
      exposure. Both UV sources inhibited IFN-gamma-induced ICAM-1 mRNA expression in a
      dose-dependent fashion. By using a Schott WG 335 nm filter, inhibition of ICAM-1
      mRNA expression by the tanning lamp was shown to be associated with UVB exposure.
      CONCLUSIONS: These results suggest that UV sources emitting different levels of
      UVA and UVB have differential effects on the modulation of different
      immunoregulatory molecules, and indicate that there are potential interactions
      between these wavelengths.

PMID- 11453908
TI  - The influence of a topical corticosteroid on short-contact high-dose dithranol
      therapy.
AB  - BACKGROUND: Dithranol (anthralin) has been known to be effective in the treatment
      of psoriasis for more than 80 years. However, perilesional and uninvolved skin
      often show irritation during dithranol treatment, which limits its use. As the
      relapse rate of psoriasis is worsened by adding corticosteroids to a dithranol
      regimen, the use of topical corticosteroids to reduce dithranol irritation is
      controversial. OBJECTIVES: The aim of the present study was to investigate the
      clinical and cell biological effect of clobetasol-17-propionate 0.05% ointment on
      dithranol-treated lesional and perilesional skin. METHODS: For 17 consecutive
      days, 2% dithranol cream was applied on two test sites. A third site was left
      untreated on all participating patients (n = 8). All sites consisted of a
      psoriasis lesion as well as a 3-cm zone of perilesional skin localized on the
      back. After 1 h, the cream was washed off, and subsequently one of the dithranol
      treated sites was treated once a day with clobetasol-17-propionate 0.05%
      ointment. The second site was treated once daily with the vehicle. On day 17,
      punch biopsies were taken from all three lesions and from the perilesional zone
      of all test sites in order to perform an immunohistochemical investigation, using
      markers to assess proliferation, differentiation and inflammation. RESULTS: The
      SUM score (erythema + induration + scaling) of the lesion treated with
      dithranol/clobetasol showed a pronounced reduction, which was significantly
      greater than the SUM score of the lesion treated with dithranol/vehicle. However,
      the scores of both sites were equal by 6 weeks of follow-up. Comparing the two
      treated lesions, we observed a lower number of cycling epidermal cells in the
      dithranol/clobetasol lesion and a significantly lower perivascular dermal score
      of T lymphocytes. Comparing the perilesional skin of the two treated sites we
      observed less cycling epidermal cells in the dithranol/clobetasol-treated site.
      Regarding perilesional differentiation, the interpapillary involucrin expression
      was higher in the dithranol/clobetasol-treated site. With respect to perilesional
      inflammation the expression of dermal polymorphonuclear leucocytes, monocytes,
      macrophages and T lymphocytes in the dermal infiltrate were significantly lower
      in the dithranol/clobetasol-treated site. CONCLUSIONS: The addition of clobetasol
      17-propionate enhanced the antipsoriatic efficacy of dithranol by interfering
      with T-cell accumulation and epidermal proliferation. The addition of a
      corticosteroid reduced perilesional dithranol inflammation at the cellular level,
      although clinically detectable dithranol erythema was not reduced.

PMID- 11453909
TI  - Double-blind placebo-controlled house dust mite control measures in adult
      patients with atopic dermatitis.
AB  - BACKGROUND: Avoidance of allergens has been shown to be of benefit in patients
      with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is
      so far little information about the effect of house dust mite elimination
      strategies. OBJECTIVES: We therefore performed a randomized controlled study of
      house dust mite control in patients with this disease. METHODS: Twenty adult
      patients with moderate to severe atopic dermatitis were included. Inclusion
      criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a
      concentration of > 2 microg g(-1) of the house dust mite antigen Der p1 in the
      patient's mattress dust. Patients were randomized to either the active treatment
      group (allergen-impermeable mattress encasing, acaricide spray containing tannic
      acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray
      containing water and traces of ethanol). Severity of disease was estimated every
      2 months by an established score (SCORAD), and eosinophil cationic protein (ECP)
      in the serum was determined by enzyme-linked immunosorbent assay. Furthermore,
      the use of topical steroids was quantified. Patients assessed daytime pruritus
      and pruritus-induced sleeplessness weekly on a visual analogue scale. The study
      lasted 1 year. RESULTS: At the end of the study, the active treatment group
      showed a statistically significant reduction in Der p1 exposure as compared with
      the control group. However, when comparing the change from the start to the end
      of the study, there was no statistically significant difference between active
      treatment and control groups as measured by the SCORAD score and by ECP levels in
      the serum. Some patients in the active treatment group reported less pruritus
      induced sleeplessness, but there was no statistically significant difference
      between the two treatment groups. CONCLUSIONS: For adult patients with atopic
      dermatitis it was shown that 1 year of house dust mite avoidance reduced the
      allergen exposure, but an improvement of overall disease activity was not
      demonstrated.

PMID- 11453910
TI  - Photodynamic therapy with meta-tetrahydroxyphenylchlorin for basal cell
      carcinoma: a phase I/II study.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a convenient and effective method of
      treating small superficial tumours. New second-generation photosensitizers offer
      some advantages over first-generation sensitizers such as haematoporphyrin
      derivatives. OBJECTIVES: To define the optimal treatment parameters (drug dose,
      light dose and time interval) using meta-tetrahydroxyphenylchlorin (mTHPC) as a
      photosensitizer in patients with multiple basal cell carcinomas (BCCs). METHODS:
      Light of 652 nm (100 mW cm(-2)) was used for illuminating different tumours (n =
      187) with light doses of 5--15 J cm(-2). Following an intravenous injection of
      0.1 mg kg(-1) mTHPC each patient (n = 5) was illuminated on 4 consecutive days.
      Each day at least three BCCs per patient were treated with PDT. RESULTS: Response
      evaluation at 6, 12 and 18 months showed maximum responses for illumination with
      10 or 15 J cm(-2) on days 1 or 2 after injection (86% complete responses). Normal
      tissue reactions (oedema and erythema) around the treatment site were more severe
      on day 1 than after longer intervals. CONCLUSIONS: mTHPC is a very effective
      photosensitizer; short illumination times can result in long-term cures with good
      cosmetic healing and with skin phototoxicity of short duration.

PMID- 11453911
TI  - Both the flashlamp-pumped dye laser and the long-pulsed tunable dye laser can
      improve results in port-wine stain therapy.
AB  - BACKGROUND: At present, laser therapy of port-wine stains (PWS) using the
      flashlamp-pumped dye laser (FPDL) at 450 micros is accepted as the optimal
      approach. A few years ago, a new long-pulsed tunable dye laser (LPTDL, 1.5 ms)
      was introduced for the treatment of leg veins. OBJECTIVES: To investigate the
      efficacy and side-effects of FPDL vs. LPTDL therapy of PWS. METHODS: Sixty-two
      patients with untreated PWS underwent test treatments with the FPDL (585 nm; 7-mm
      spot size; 5.75--7.0 J cm(-2) fluence) and LPTDL (585, 590, 595, 600 nm; 5-mm
      spot size; 11--20 J cm(-2) fluence). With the LPTDL, the epidermis was
      additionally cooled (Spray cooling device). The fading was evaluated clinically 6
      weeks after the test treatments. RESULTS: Optimal fading was achieved by the
      LPTDL (> or = 585 nm) in 30 patients and by the FPDL in 12 patients. No
      difference was found in 20 patients. At 585 nm, the lasers worked equally well in
      12 (FPDL) and 13 (LPTDL) patients, respectively. Results were independent of the
      localization of the PWS and of the patient's age. In spite of the longer pulse
      duration, the LPTDL treatment did not result in more side-effects as long as
      sufficient cooling was provided. CONCLUSIONS: The results provide evidence that
      wavelengths longer than 585 nm can increase the efficacy of treatment in some
      PWS. Owing to the reduced light absorption by haemoglobin at longer wavelengths
      and consequently increased depth of the vascular injury, larger vessels can be
      damaged more adequately using an increased fluence. The LPTDL at 585 nm seemed to
      be slightly superior to the FPDL, while accepting that due to technical reasons
      the laser parameters were not directly comparable. Availability of both lasers
      increases the therapeutic possibilities in PWS.

PMID- 11453912
TI  - High incidence of lichen sclerosus in patients with squamous cell carcinoma of
      the penis.
AB  - BACKGROUND: There is a well-documented association between lichen sclerosus (LS)
      and vulval carcinoma in women; however, until recently, there have only been
      anecdotal reports of penile squamous cell carcinoma (SCC) occurring in men with
      LS. OBJECTIVE: The incidence of penile carcinoma occurring on a background of LS
      remains uncertain, and we wished to examine this possible association further.
      METHOD: To address this, all the cases (n = 20) of penile SCC held on our
      pathology database (4 years) were examined. Histology was reviewed, blind to the
      clinical picture, for evidence of LS, applying strict histological criteria.
      Subsequently, clinical notes were reviewed for history of LS before the SCC
      presented, and history of previous circumcision, treatments, node involvement,
      metastases and death. RESULTS: In eight cases, evidence of LS was found in the
      excision specimen. Seven of these had well-differentiated SCC. In the 12 cases
      with no evidence of LS, only three were well differentiated. With case note
      review, seven had a history of LS (four with histological LS), sometimes
      preceding the SCC by 10 years. These all had well-differentiated SCC. Ten of the
      20 patients are dead, seven from metastatic disease. Four deaths occurred in the
      'well-differentiated LS' group, but only one from penile SCC metastatic disease.
      CONCLUSIONS: There appears to be a definite association between SCC of the penis
      and the presence of LS, similar to that reported between LS and vulval SCC in
      women. Of the 20 patients with penile SCC studied, 11 had a clinical history
      and/or histological evidence of LS. However, clinical presentation of the LS or
      need for circumcision may precede the SCC by many years. As follow-up is
      impractical, counselling at the time of diagnosis is very important, and it is
      essential that medical practitioners are aware of this association so that the
      subsequent risk from SCC is reduced.

PMID- 11453913
TI  - Linkage and association of HLA class II genes with vitiligo in a Dutch
      population.
AB  - BACKGROUND: Serological typing of HLA has shown discrepancies in HLA associations
      with vitiligo in different ethnic populations. OBJECTIVES: To perform genotyping
      of HLA class II genes on a Dutch vitiligo population in order clearly to identify
      susceptible and protective HLA alleles in vitiligo. METHODS: HLA typing was
      carried out by amplifying genomic DNA by polymerase chain reaction (PCR) followed
      by dot-blot hybridization with sequence-specific oligonucleotides (SSO). Fifty
      Dutch vitiligo probands, and their parents (150 individuals) and 204 healthy
      controls were studied. RESULTS: Family-based case-control association studies and
      linkage disequilibrium analysis showed the linkage and association of DRB4*0101
      allele with vitiligo (P(c) = 0.0016, relative risk = 2.21). The family-based
      association study also provided evidence for linkage and association of DQB1*0303
      allele with vitiligo (chi(2) = 7.36, P = 0.006). We measured the clinical
      relevance of the test by calculating the prevalence corrected positive predictive
      values (PcPPV). The PcPPV of disease for the DRB4*0101 allele was 0.017 and for
      the DRB4*0101/0101 genotype was 0.0358. In other words, a DRB4*0101/0101 genotype
      carries a 3.58% risk of developing vitiligo. CONCLUSIONS: Both DRB4*0101 and
      DQB1*0303 alleles provide significant susceptibility for vitiligo.

PMID- 11453914
TI  - The prevalence and types of androgenetic alopecia in Korean men and women.
AB  - BACKGROUND: There are racial differences in the prevalence and types of
      androgenetic alopecia (AGA). There have been several reports on the prevalence
      and types of AGA in the general population of caucasians, but few studies on
      Koreans with samples of sufficient numbers have been reported. OBJECTIVES: To
      obtain a more precise estimate of the prevalence and types of AGA in Korean men
      and women and to compare the results with those in caucasians. METHODS: The
      prevalence and types of AGA were analysed in 10,132 Koreans (5531 men and 4601
      women) who had visited the Health Examination Centre at Kyung Hee University
      Hospital for regular health examinations between December 1997 and July 1999. To
      classify the degree of hair loss for each subject, the Norwood classification was
      used in men and the Ludwig classification in women. For AGA in men, 'female
      pattern' was added to the Norwood classification. RESULTS: In Korean men, the
      prevalence of AGA (Norwood III or above) at all ages was 14.1%. It increased
      steadily with advancing age, but was lower than that of caucasians: 2.3% in the
      third decade, 4.0% in the fourth decade, 10.8% in the fifth decade, 24.5% in the
      sixth decade, 34.3% in the seventh decade and 46.9% over 70 years. Type III
      vertex involvement was the most common type in the third decade to the seventh
      decade; over 70 years, type VI was most common. A 'female pattern' was observed
      in 11.1% of cases. In Korean women, the prevalence of AGA (Ludwig I or above) at
      all ages was 5.6%. It also increased steadily with advancing age: 0.2% in the
      third decade, 2.3% in the fourth decade, 3.8% in the fifth decade, 7.4% in the
      sixth decade, 11.7% in the seventh decade and 24.7% over 70 years. Grade I was
      the most common type up to the sixth decade; over 60 years, grade I and II were
      similar in prevalence. Grade III (total baldness) was not observed. A family
      history of baldness was present in 48.5% of men and 45.2% of women with AGA.
      CONCLUSIONS: The prevalence of AGA in Korean men and women was lower than that in
      caucasians, as recorded in the literature. Korean men tend to have more frontal
      hairline preservation and show a more 'female pattern' of hair thinning than
      caucasians. Therefore, 'female pattern' should be added to the classification of
      AGA.

PMID- 11453915
TI  - Epidemiology of acne in the general population: the risk of smoking.
AB  - BACKGROUND: Acne is a common skin disorder, but epidemiological data from the
      general population obtained by examination are scarce. Clinical experience
      suggests an association between smoking and acne, although confirmatory evidence
      from appropriate studies is lacking. OBJECTIVES: To determine the prevalence and
      demographic factors of acne in a general population sample and to investigate the
      association of smoking and acne on a qualitative and quantitative level. METHODS:
      In a cross-sectional study, 896 citizens (aged 1--87 years, median 42) of the
      City of Hamburg were dermatologically examined. The prevalence and severity of
      acne were recorded and further information on demographic variables, medical
      history, and alcohol and cigarette consumption were obtained by a standardized
      interview. RESULTS: According to the clinical examination, acne was present in
      26.8% overall, and was more prevalent in men (29.9%) than women (23.7%) (odds
      ratio, OR 1.37, 95% confidence interval, CI 1.01--1.87). Prevalence followed a
      significant linear trend over age with peak prevalence between 14 and 29 years (P
      < 0.001). The reported age at onset was significantly lower in women than men (P
      = 0.015). According to multiple logistic regression analyses acne prevalence was
      significantly higher in active smokers (40.8%, OR 2.04, 95% CI 1.40--2.99) as
      compared with non-smokers (25.2%). A significant linear relationship between acne
      prevalence and number of cigarettes smoked daily was obtained (trend test: P <
      0.0001). In addition, a significant dose-dependent relationship between acne
      severity and daily cigarette consumption was shown by linear regression analysis
      (P = 0.001). CONCLUSIONS: Smoking is a clinically important contributory factor
      to acne prevalence and severity.

PMID- 11453916
TI  - Nodular localized primary cutaneous amyloidosis: a long-term follow-up study.
AB  - We present long-term follow-up data on patients with nodular localized primary
      cutaneous amyloidosis (NLPCA) seen at the St John's Institute of Dermatology
      between 1968 and 1999. This is the largest clinical follow-up study of this type
      of amyloid to date. Based on these cases we estimate the rate of progression of
      NLPCA to systemic amyloidosis to be only 7%, much lower than the 50% rate
      currently quoted in the literature.

PMID- 11453917
TI  - Dissatisfaction with skin appearance among patients with eating disorders and non
      clinical controls.
AB  - BACKGROUND: We have recently observed that women with the eating disorders (EDs)
      anorexia nervosa and bulimia nervosa report a significantly greater (P = 0.002)
      dissatisfaction with the appearance of their skin than do non-clinical controls.
      OBJECTIVES: To examine further the nature of the dissatisfaction with skin
      appearance in women with EDs. METHODS: Several psychosocial and body image
      parameters, including whether or not the subjects were satisfied with a wide
      range of attributes associated with non-diseased skin, were surveyed in women
      aged < or = 30 years. Survey data from 32 women with EDs and 34 randomly selected
      community-based non-clinical controls were examined. RESULTS: Eighty-one per cent
      of the patients with EDs vs. 56% of the controls reported dissatisfaction with
      the appearance of their skin (P = 0.03), particularly with respect to its dryness
      and roughness. Other attributes that were rated more frequently were 'bags' and
      'darkness' under the eyes, freckles, fine wrinkles and patchy hyperpigmentation.
      CONCLUSIONS: There is a high prevalence of dissatisfaction with skin appearance
      among women aged < or = 30 years, which is even higher among patients with EDs.

PMID- 11453918
TI  - Identification of Mycobacterium marinum in sea-urchin granulomas.
AB  - BACKGROUND: Sea-urchin granuloma is a chronic granulomatous reaction arising
      after injury with sea-urchin spines. Classified as an allergic foreign-body type
      of granuloma, it is believed to be a delayed-type reaction to an as yet
      unidentified antigen. In a clinicopathological study, 50 biopsy specimens from 35
      patients diagnosed as having sea-urchin granuloma caused by Paracentrotus
      lividus, we found different inflammatory patterns that in some cases suggested a
      mycobacterial infection. OBJECTIVES: To investigate and identify mycobacterial
      DNA in formalin-fixed and paraffin-embedded skin biopsy specimens diagnosed as
      sea-urchin granulomas. METHODS: A search combining polymerase chain reaction
      amplification using Mycobacterium genus-specific primers, and subsequent
      restriction enzyme analysis enabling identification to the species level, was
      performed in 41 samples. RESULTS: Amplification of a 924-bp DNA fragment encoding
      mycobacterial 16S rRNA gene was positive in eight biopsy specimens from seven
      patients (21%). M. marinum-specific restriction patterns were identified in three
      samples. CONCLUSIONS: Although further controlled studies are necessary, from
      these data it would appear that mycobacteria may play a pathogenic role in some
      cases of sea-urchin granuloma.

PMID- 11453919
TI  - A case of adult T-cell leukaemia/lymphoma characterized by multiplex-fluorescence
      in situ hybridization, comparative genomic hybridization, fluorescence in situ
      hybridization and cytogenetics.
AB  - Adult T-cell leukaemia/lymphoma (ATLL) is a neoplasm of mature helper (CD4) T
      lymphocytes. Little is known, however, about the chromosome aberrations
      associated with the pathogenesis of this malignancy. Using molecular cytogenetic
      techniques we, therefore, investigated a 44-year-old man who had a 7-year history
      of ATLL with cutaneous involvement mimicking primary cutaneous T-cell lymphoma.
      Conventional cytogenetics revealed gross chromosomal changes with chromosome
      numbers ranging from 71 to 82. There were structural abnormalities of chromosomes
      7 and 9, partial deletions of chromosomes 1, 3, 5 and 6, and loss of chromosomes
      2, 4, 9, 11--14, 21 and 22. Multiplex-fluorescence in situ hybridization (M-FISH)
      identified two derivative chromosomes, der(6)t(6;7)(q16;q21) and
      der(7)t(6;7)(q16;q21)ins(6;12)(q2?;?), and a deletion of chromosome 1p.
      Conventional FISH confirmed the M-FISH findings. Comparative genomic
      hybridization of the blood revealed gains of DNA copy number at 1q12--25, 6p24-
      25, 9p23, 16p13--q13, 17q11--21, 19p13 and 20q13 and loss at 11p15 while lymph
      nodes showed gains at 3p22--24, 3q27--29, 7q36 and 15q26 and losses at 2p24--25,
      2q37, 10p14--15, 11p15, 13q33--34 and 16p13.3. No DNA copy number changes were
      seen in a skin lesion. These results show the extent of genetic abnormalities
      within this malignancy.

PMID- 11453920
TI  - CD30+ lymphoproliferative disorder: primary cutaneous anaplastic large cell
      lymphoma followed by lymphomatoid papulosis.
AB  - CD30+ large anaplastic lymphoid cells are seen in anaplastic large cell lymphoma
      (ALCL), and also in lymphomatoid papulosis (LyP) and other lymphoproliferative
      disorders. It can be difficult precisely to categorize these disorders with CD30+
      cells. We report a case of primary cutaneous CD30+ ALCL with systemic metastases
      in whom the clinical disease subsequently evolved into LyP. The patient was
      initially administered cisplatin and etoposide and made a good response. Eighteen
      months later, recurrent, self-healing cutaneous small nodules appeared around the
      original tumour site without any systemic involvement. Histopathological
      examination of the recurrent lesions revealed infiltration with a mixture of
      cells that included neutrophils, eosinophils and CD30+ large anaplastic cells
      cytologically identical with those in the primary lesion. The anaplastic cells in
      both the primary and recurrent lesions were positive for monoclonal antibodies
      CD30, CD25 and a monoclonal antibody directed against the chimeric protein
      p80(NPM-ALK). These observations suggest the possibility that the ALCL and the
      subsequent LyP represent different clinical manifestations of proliferation of
      the same clone.

PMID- 11453921
TI  - Paraneoplastic pemphigus. A report of two cases associated with chronic B-cell
      lymphocytic leukaemia.
AB  - Paraneoplastic pemphigus (PNP) is an autoimmune blistering and erosive
      mucocutaneous disease associated with neoplasia. Clinical manifestations are
      polymorphous, and include erythema, bullae, erythema multiforme-like lesions and
      severe mucous membrane involvement. PNP manifesting as lichenoid dermatitis has
      recently been observed. We describe two Italian men with fatal PNP featuring
      typical PNP autoantigens associated with chronic B-cell lymphocytic leukaemia.
      The first patient presented with an extensive blistering eruption, several
      erythema multiforme-like lesions and severe mucosal involvement. The second
      patient presented with a lichenoid dermatitis, then developed bullae, and died
      with an erythrodermic and exfoliative dermatosis resembling pemphigus foliaceus.
      Our patients represent two Italian cases of well-documented PNP. In patient 2,
      the sequence of clinical presentations was unique, and strongly supports the
      hypothesis of epitope spreading through chronic lichenoid inflammation of the
      dermo-epidermal junction exposing new self antigens, leading to the humoral
      response characteristic of PNP.

PMID- 11453922
TI  - Pemphigus foliaceus with prominent neutrophilic pustules.
AB  - We describe four patients with generalized scaly and pustular skin lesions
      showing extensive neutrophilic infiltration in the subcorneal region of the
      epidermis. Immunofluorescence, immunoblot and enzyme-linked immunosorbent assay
      analyses detected IgG antibodies reacting exclusively with desmoglein 1, the
      pemphigus foliaceus antigen. This study indicates that pemphigus foliaceus may
      show prominent neutrophilic pustular skin lesions.

PMID- 11453923
TI  - Successful treatment of cutaneous Langerhans cell histiocytosis with low-dose
      methotrexate.
AB  - Langerhans cell histiocytosis (LCH) can be a difficult therapeutic problem. We
      present a 40-year-old woman with a 4-year history of LCH who was successfully
      treated with low-dose methotrexate (20 mg weekly).

PMID- 11453924
TI  - Reticular erythematous mucinosis syndrome with an infiltration of factor XIIIa+
      and hyaluronan synthase 2+ dermal dendrocytes.
AB  - We report a patient with reticular erythematous mucinosis (REM) syndrome. Content
      of hyaluronan in lesional skin was approximately 2.9-fold higher than in the
      patient's uninvolved skin, but its synthetic activity in fibroblasts explanted
      from lesional skin remained unchanged. Immunohistochemical study using antifactor
      XIIIa (anti-FXIIIa) antibody demonstrated that the number of FXIIIa+ cells in the
      lesional skin was significantly increased compared with those in the patient's
      uninvolved skin and in normal control skin samples (P < 0.01). As hyaluronan is
      considered to be synthesized by hyaluronan synthase (HAS), which is composed of
      three genetically distinct isoforms (HAS1, HAS2 and HAS3), the cells responsible
      for the accumulation of hyaluronan in lesional skin were immunohistochemically
      examined using antibodies for HAS1, HAS2 and HAS3. The specific antibody for HAS2
      was found to react with some populations of FXIIIa+ cells in the involved skin,
      and the number of HAS2+ cells was significantly increased in the involved skin (P
      < 0.01). The results suggest that accumulation of hyaluronan in REM may be
      related to populations of FXIIIa+/HAS2+ dermal dendrocytes rather than to dermal
      fibroblasts.

PMID- 11453925
TI  - Cowpox virus in a 12-year-old boy: rapid identification by an orthopoxvirus
      specific polymerase chain reaction.
AB  - Although smallpox was eradicated 20 years ago, other members of the genus
      Orthopoxvirus (OPV), such as cowpox virus (CPXV) or monkeypox virus, are still a
      threat to humans. Because human CPXV infection is rare, it is seldom suspected on
      clinical grounds only. We report a boy who presented with two necrotic ulcers
      with surrounding erythema. Infection with OPV was suspected, as antibiotic
      treatment had not produced improvement and smears were negative for anthrax. An
      OPV was isolated and an OPV-specific polymerase chain reaction combined with a
      subsequent restriction enzyme fragment length polymorphism assay confirmed
      infection by CPXV. Although the patient's cat had had no skin lesions, OPV
      specific antibodies were found at a titre of 1 : 8 in a plaque reduction assay,
      suggesting that the cat had transmitted the virus to the boy.

PMID- 11453926
TI  - Dermatophyte pseudomycetoma of the scalp: case report and review.
AB  - We report the first case of a scalp pseudomycetoma due to Trichophyton
      schoenleinii in a 15-year-old girl from Senegal. The lesion was not associated
      with tinea capitis. Long-term antifungal therapy with itraconazole and
      terbinafine was unsuccessful but a favourable outcome was obtained after surgical
      removal of the lesion. Between 1973 and 1999, only 12 previous cases of
      dermatophyte pseudomycetoma of the scalp were reported in the literature.
      Clinical features and therapeutic outcomes of these cases are reviewed.

PMID- 11453927
TI  - Primary cutaneous nocardiosis due to Nocardia nova in a healthy woman.
AB  - We describe a 68-year-old healthy woman with an unusual skin manifestation of
      mycetoma. A dark reddish erythematous plaque was present on the dorsum of the
      left hand for over 10 years. A skin biopsy revealed sulphur granules in the
      abscess, and Nocardia nova was identified from the specimen. Treatment with
      dapsone resulted in significant improvement. We review the clinical features of
      cutaneous N. nova infections.

PMID- 11453928
TI  - Woolly hair, premature loss of teeth, nail dystrophy, acral hyperkeratosis and
      facial abnormalities: possible new syndrome in a Dutch kindred.
AB  - We describe a Dutch kindred with a possibly novel dominant syndrome of premature
      loss of curly, brittle hair, premature loss of teeth due to caries, nail
      dystrophy and acral keratoderma. We discuss the possibility that this ectodermal
      dysplasia of group 1-2-3-4 is a variant of known disorders such as pachyonychia
      congenita. We conclude that none of these diagnoses fits the symptoms we observe
      in our patients and propose the name curly hair-acral keratoderma-caries syndrome
      in view of the most obvious abnormalities.

PMID- 11453929
TI  - Granulomatous variant of chronic pigmented purpuric dermatosis: report of two
      cases.
AB  - Two patients presenting with chronic pigmented purpuric dermatosis (CPPD) on the
      dorsum of both feet were found to show granulomatous inflammation superimposed on
      the pathological changes of CPPD. Two similar cases have been reported from
      Japan. The unique clinicopathological features of this group of patients suggest
      that they have a rare granulomatous variant of CPPD.

PMID- 11453930
TI  - Necrotizing infundibular crystalline folliculitis.
AB  - We describe a 22-year-old woman with a background of acne who developed multiple
      folliculocentric facial papules associated with sharply demarcated waxy,
      keratotic plugs. Multiple skin biopsies showed umbilicated craters that were
      filled with dispersed bundles of eosinophilic filaments embedded in a pale
      amorphous matrix forming a plug. The plugs bulged into the upper dermis. Serial
      sections showed vacuolar and filamentous destruction of the infundibular and
      adjacent perifollicular epithelium and a close relationship of the crystalline
      necrosis to follicles. Electron microscopy revealed that the filamentous bundles
      were tonofilaments. No fresh material was available for polarization and the
      paraffin sections failed to polarize. The clinical and pathological findings of
      the lesions in our patient were identical to those reported as a new perforating
      disorder with urate-like crystals. Our case indicates that the process may
      represent crystalline folliculocentric necrosis rather than a primary perforating
      disorder. The nature and basis of the crystals that have a urate-like appearance
      remain to be determined.

PMID- 11453931
TI  - Effective removal of sea-urchin spines by erbium: YAG laser ablation.

PMID- 11453932
TI  - Human dermatophilosis mimicking ringworm.

PMID- 11453933
TI  - Novel intracytoplasmic inclusion bodies in human papillomavirus-associated warts.

PMID- 11453934
TI  - Acquired perforating collagenosis: is it due to damage by scratching?

PMID- 11453935
TI  - Treatment of acquired reactive perforating collagenosis with allopurinol.

PMID- 11453936
TI  - An alopecic phenotype of canine pemphigus vulgaris?

PMID- 11453937
TI  - The use of two substrates for indirect immunofluorescence in the diagnosis of
      pemphigus.

PMID- 11453939
TI  - gamma-Gliadin: a presumptive allergen causing wheat-dependent exercise-induced
      anaphylaxis.

PMID- 11453940
TI  - Systems dermatology and clinical dermatological research.

PMID- 11453941
TI  - Cutaneous malignancy in arsenicosis.

PMID- 11453942
TI  - Antioxidant characteristics of chronic wound fluid.

PMID- 11453943
TI  - Atypical presentation of adult Still's disease with generalized rash and
      hyperferritinaemia.

PMID- 11453944
TI  - Linear focal elastosis.

PMID- 11453945
TI  - Apoptosis and autoimmune thyroid disease: following a TRAIL to thyroid
      destruction?

PMID- 11453946
TI  - Stressful life events and Graves' disease revisited.

PMID- 11453947
TI  - Relationship between the number and impact of stressful life events and the onset
      of Graves' disease and toxic nodular goitre.
AB  - BACKGROUND: In the last few decades, several studies have suggested a possible
      association between Stressful Life Events (SLEs) and the onset of Graves' Disease
      (GD). However, others have criticised this association and it has not yet been
      possible to prove it unequivocally. At present, we are not aware of studies
      correlating SLE and non autoimmune thyrotoxicosis. OBJECTIVE: To assess possible
      associations between SLEs, the onset of GD and the onset of non autoimmune
      thyrotoxicosis (toxic nodular goitre, TNG). DESIGN: A case-control retrospective
      study. PATIENTS: This study included 93 subjects, divided into three groups of 31
      each: GD, TNG and control (CG). The GD and TNG patients had thyroid disease
      diagnosed within the last 12 months, with clinical and biochemical confirmation.
      In the CG, psychopathological and endocrine disturbances had been ruled out. All
      three groups consisted of nine males (29%) and 22 females (71%). The mean age was
      38.4 +/- 10.9 years in the GD group, 48.3 +/- 11.1 years in the TNG group and
      41.1 +/- 11.8 years in the CG group. SLEs were evaluated (number and impact) for
      the 12 months preceding the onset of symptoms of thyroid disease. MEASUREMENTS:
      SLE occurrences and their impact on each group of cases were measured. To assess
      SLEs, we used the Life Experiences Survey (LES). Our statistical analysis
      included descriptive techniques and parametric and/or nonparametric comparative
      tests. P < 0.01 was considered statistically significant. Odds ratios were also
      calculated. RESULTS: Patients with GD had a significantly greater number of SLEs
      compared to the TNG group and the CG (P < 0.001). The number and impact of
      negative SLEs were significantly higher in GD compared to TNG and CG (P < 0.001).
      The difference between TNG and CG was not significant (P > 0.01). GD had a higher
      impact of positive SLEs than TNG (P = 0.004), and no significant differences were
      found between the GD group and CG. Neutral SLEs were similar in the three groups.
      CONCLUSIONS: These results suggest that SLEs are a precipitating factor of the
      onset of GD. We also demonstrated that SLEs do not seem to have any conclusive
      relationship with the onset of TNG.

PMID- 11453948
TI  - Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the
      significance of prophylactic cranial irradiation.
AB  - OBJECTIVE: Focus on long-term side-effects after cancer therapy in childhood has
      become of the utmost importance. The hypothalamic-pituitary thyroid (HPT) axis is
      exposed to irradiation when some children are treated for acute lymphoblastic
      leukaemia (ALL) with prophylactic cranial irradiation (CIR). Whether this
      treatment causes hypofunction of the HPT axis remains controversial. DESIGN: We
      measured plasma levels of total T3 (T3), total T4 (T4) and TSH before stimulation
      with TRH and plasma levels of TSH, 30 and 150 minutes after stimulation with TRH
      in 95 patients in first continuous remission of childhood ALL. PATIENTS: Patients
      diagnosed with ALL before the age of 15 years between 1970 and 1991 and who were
      in first continuous remission and off treatment for at least one year were
      studied. The children were aged between 0.5 and 14.8 years (median: 3.9) at
      diagnosis of ALL. Thyroid function was assessed between 1.2 and 18.3 years
      (median: 7.6) after completion of therapy. MEASUREMENTS: We measured T4 levels
      before, and compared TSH levels before and after, stimulation with TRH in
      patients who were treated with prophylactic CIR (15-24 Gy) (n = 38) (CIR group)
      with patients who were treated with chemotherapy only (n = 57) (non-CIR group).
      RESULTS: We found that T3 and T4 levels were normal in all individuals (excluding
      the women who were on oral contraceptives). The median time from end of treatment
      to time at follow-up was 9.1 years in the non-CIR group vs. 4.2 years in the CIR
      group (P < 0.001), and the effect on follow-up time was significant (P = 0.04).
      It was estimated that just after irradiation, the TSH levels before and 30 and
      150 minutes after TRH stimulation was 49% lower in the CIR group; however, after
      4.0 years, TSH levels were not significantly different between the two groups.
      Although within normal limits, the T4 levels were significantly higher in the CIR
      group compared to the non-CIR group (P = 0.003). It was estimated that, just
      after the end of treatment, T4 was 19.9% higher in the CIR group. However, in the
      CIR group, the T4 level decreased significantly over time with -1.5% per year (P
      = 0.025), while the difference in the non-CIR group was not significant. There
      was no correlation between T4 and TSH levels and sex, age at diagnosis, age at
      the end of treatment or age at follow-up. CONCLUSIONS: We conclude that, in our
      cohort of survivors of childhood ALL, prophylactic cranial irradiation of the
      central nervous system did not have an adverse effect on hypothalamo-pituitary
      thyroid function within a median follow-up time of 8 years.

PMID- 11453949
TI  - Hyperthyroidism is associated with lengthening of ventricular repolarization.
AB  - OBJECTIVE: Lengthened ventricular repolarization, as assessed by the QT interval
      on electrocardiogram (ECG), can predispose to an increased risk of cardiac
      dysrhythmias; no data are available on QT corrected for heart rate (QTc) in
      hyperthyroidism in vivo. DESIGN: QT and RR intervals from 24 h ambulatory ECG
      Holter recording were measured in patients with hyperthyroidism and again
      following pharmacological achievement of stable euthyroidism for at least 2
      months. PATIENTS: We enrolled a total of 16 hyperthyroid patients with Graves'
      disease, six males and 10 females (mean age 47 +/- 4 years, mean +/- SEM); 13
      healthy age- and sex-matched subjects were utilized as a control group.
      MEASUREMENTS: The QT analysis was carried out by a computerized algorithm (QTc
      was corrected by the heart rate by Bazett's formula). Serum total T4, total T3,
      free T4, free T3 and TSH concentrations were measured by a fully automated
      immunoenzymometric assay; plasma norepinephrine by automatized high-pressure
      liquid chromatography, potassium and chloride by a potentiometric method,
      magnesium and calcium by a colourimetric method. RESULTS: The 24-h average QTc in
      the hyperthyroid patients was significantly prolonged compared to controls (458
      +/- 7 vs. 431 +/- 6 ms, P = 0.01) and it returned to normal after treatment of
      thyrotoxicosis (432 +/- 6 ms, P < 0.05 vs. time H, NS vs. controls). QTc
      positively correlated with FT3 (r = 0.63, P < 0.001) and with FT4 (r = 0.481, P <
      0.02). Conversely, QTc did not correlate with plasma basal norepinephrine levels,
      nor with electrolytes. CONCLUSIONS: Hyperthyroidism is associated with prolonged
      QTc that normalizes once the patient becomes euthyroid. The strong positive
      correlation between FT3 and QTc supports the hypothesis of an important role of
      thyroid hormone on modulation of QTc lengthening.

PMID- 11453950
TI  - The nature of human chorionic gonadotrophin glycoforms in gestational
      thyrotoxicosis.
AB  - OBJECTIVE: We examined the charge heterogeneity and carbohydrate complexity of
      hCG in healthy pregnant Asian subjects and Asian women with gestational
      thyrotoxicosis to assess whether particular glycoforms of hCG are associated with
      the thyrotoxicosis of pregnancy. DESIGN: Blood was taken at 8-16 weeks of
      gestation from five pregnant Asian women with clinical symptoms of gestational
      thyrotoxicosis and biochemical indicators of hyperthyroidism and from six age
      matched healthy pregnant women. hCG charge heterogeneity and carbohydrate
      complexity were assessed by fast protein liquid chromatography chromatofocusing
      and concanavalin A affinity chromatography, respectively. The degree of terminal
      sialylation of the different glycoforms was measured by ricin affinity
      chromatography, which detects exposed galactose residues following desialylation.
      RESULTS: Free T3, free T4 and hCG levels were elevated and TSH suppressed in the
      thyrotoxic subjects compared to controls (P < 0.007). Overall, the glycoform
      distribution of the hCG in the blood from the control and thyrotoxic groups was
      similar, with a median pI of 4.34 (median and range: 3.78-4.68) and pI 4.23 (3.98
      4.38). Free T4 (P < 0.028) and free T3 (P < 0.03) levels were positively
      correlated to both the absolute hCG concentration and the percentage of hCG forms
      between pI 3.36-4.0. The distribution of simple (73-88.6%), intermediate (9.7
      26.4%) and complex (0.1-7.3%) branching oligosaccharide forms was similar in both
      groups, as was the percent hCG which bound to ricin (< 3.2%). CONCLUSION: We
      conclude that excessive thyroid stimulation in the thyrotoxic patients is
      associated both with the absolute concentration of hCG and the relative
      proportion of acidic glycoforms between pI 3.36 and 4.0.

PMID- 11453951
TI  - Alcohol consumption is associated with reduced prevalence of goitre and solitary
      thyroid nodules.
AB  - OBJECTIVE: Goitre prevalence is dependent on iodine intake and smoking habits,
      but further risk factors have only been examined briefly. We examined the
      association between alcohol consumption and the prevalence of thyroid enlargement
      and nodularity. DESIGN: Cross-sectional population study with ultrasonography of
      the thyroid gland and assessment of alcohol intake and smoking habits from
      questionnaires. SUBJECTS: Four thousand six-hundred and forty-nine men and women
      aged 18-65 years, randomly selected from the Danish Civil Registration System.
      MEASUREMENTS: Thyroid volume and prevalence of thyroid enlargement, multiple
      nodules or a solitary nodule in the thyroid. RESULTS: Abstainers and participants
      with a low alcohol consumption (< 7 drinks/week) had the same prevalence of
      thyroid enlargement and nodularity, but participants with moderate (8-28
      drinks/week for women, 8-42 for men) or high (> 28/42 drinks/week) alcohol
      consumption had much lower prevalence of thyroid abnormalities. Possible
      confounding by sex, age, iodine status and smoking was considered in all models.
      Odds ratios compared to abstainers for thyroid enlargement were 0.74 [95%
      confidence interval (CI) 0.57-0.96] for moderate- and 0.44 (95% CI 0.22-0.88) for
      high alcohol consumption. Odds ratios compared to abstainers for a solitary
      nodule were 0.64 (95% CI 0.42-0.96) for moderate- and 0.41 (95% CI 0.12-1.37) for
      high alcohol consumption. Mean thyroid volume was 13.5 ml among abstainers
      compared to 10.9 ml among participants with high alcohol consumption (P < 0.001).
      Both wine- and beer consumption were associated to lower prevalence of thyroid
      abnormalities. CONCLUSIONS: Increasing levels of alcohol consumption were
      associated to lower prevalence of thyroid enlargement and to lower prevalence of
      a solitary nodule in the thyroid, and indications of a causal relationship were
      found.

PMID- 11453952
TI  - Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and
      medullary carcinoma of the thyroid with (131)I-meta-iodobenzylguanidine [(131)I
      mIBG].
AB  - OBJECTIVE: Meta-iodo-benzyl-guanidine labelled with 131-iodine [(131)I-mIBG] has
      been used extensively for imaging tumours originating from the neural crest but
      experience with its therapeutic use is limited, particularly for non
      catecholamine secreting tumours. In order to assess the therapeutic response and
      potential adverse effects of the therapeutic administration of (131)I-mIBG, we
      have reviewed all patients who had received this form of treatment in our
      department. DESIGN: Retrospective analysis of the case notes of patients with
      neuroendocrine tumours who received treatment with (131)I-mIBG and were followed
      up according to a defined protocol in a given time frame. PATIENTS: Thirty-seven
      patients (18 with metastatic carcinoid tumours, 8 metastatic phaeochromocytoma, 7
      metastatic paraganglioma and 4 metastatic medullary carcinoma of the thyroid)
      treated with (131)I-mIBG over a 15-year period were included in this analysis.
      MEASUREMENTS: The symptomatic, hormonal and tumoural responses before and after
      (131)I-mIBG therapy over a median follow-up duration of 32 months (range 5-180
      months) were recorded. Of the 37 patients (22 males; median age 51 years, range
      18-81 years), 15 were treated with (131)I-mIBG alone whereas the other 22
      received additional therapy. RESULTS: A total of 116 therapeutic (131)I-mIBG
      doses were administered [mean cumulative dose 592 mCi (21.9 GBq); range 200-1592
      mCi (7.4-58.9 GBq)]. None of the patients showed a complete tumour response.
      However, 82% of patients treated with (131)I-mIBG alone and 84% who received
      additional therapy showed stable disease over the period of follow-up. Overall
      survival during the period of the study was 71%. The overall 5-year survival rate
      was 85% (95% confidence interval, 72-99%) for all patients and 78% (95%
      confidence interval, 55-100%) for the carcinoid group alone, according to Kaplan
      Meier analysis. Symptomatic control was achieved in all the patients treated with
      (131)I-mIBG alone, and in 72% of those receiving additional therapy. Hormonal
      control was noted in 50% and 57% of patients, respectively. (131)I-mIBG therapy
      was safe and well tolerated. Serious side-effects necessitating the termination
      of (131)I-mIBG therapy were seen in only 2 of our patients. CONCLUSIONS: (131)I
      mIBG therapy produces symptomatic and hormonal improvement and moderate tumour
      regression/stabilization in patients with metastatic neuroendocrine tumours with
      minimal adverse effects. It may be a valuable alternative or additional
      therapeutic option to the currently available conventional treatment modalities.

PMID- 11453953
TI  - Desmopressin stimulation test before and after pituitary surgery in patients with
      Cushing's disease.
AB  - OBJECTIVE: The desmopressin test has been proposed as a useful tool for the
      differential diagnosis of Cushing's disease. The aim of our study was to
      investigate, in a large series of patients with Cushing's disease, the incidence
      of a positive ACTH and cortisol response to desmopressin. Moreover, we repeated
      the test soon after surgery to verify its usefulness in the assessment of early
      and late surgical results. PATIENTS AND METHODS: One hundred and seven
      consecutive patients with Cushing's disease, 89 female and 18 male patients, with
      a mean age of 37.2 +/- 1.3 years, were studied. All patients, except three,
      repeated the test 5-6 days after surgery. Desmopressin (10 microg) was injected
      i.v. and blood samples were drawn 15, 30, 45 and 60 minutes thereafter. Plasma
      ACTH and serum cortisol were measured in duplicate by commercially available
      immunoassays. A positive response to desmopressin was considered to be a plasma
      ACTH and serum cortisol increment of at least 30% and 20% above baseline,
      respectively. RESULTS: Mean basal plasma ACTH level was 17.3 +/- 1.7 pmol/l and
      rose to a peak level of 42.7 +/- 4.9 pmol/l at 15 minutes Mean basal serum
      cortisol level was 574 +/- 19 nmol/l and rose to a peak level of 814 +/- 28
      nmol/l at 45 minutes. ACTH and cortisol incremental changes were inversely
      correlated with their respective basal levels. Ninety patients (84.1%) had an
      ACTH and 84 patients (78.5%) had a cortisol response to desmopressin. Several
      clinical and demographic characteristics were not significantly different among
      desmopressin responders and non responders, except that basal ACTH and cortisol
      levels were significantly higher in desmopressin non responders (27.2 +/- 8.3
      pmol/l, 781 +/- 86 nmol/l) than in desmopressin responders (15.4 +/- 1.2 pmol/l,
      535 +/- 14 nmol/l). Disappearance of the ACTH and cortisol response to
      desmopressin after surgery occurred in 50 of 87 (57%) ACTH responders and in 57
      of 81 (70.4%) cortisol responders, respectively. However, concordance between the
      desmopressin test and surgical outcome was not complete. Indeed, 18 patients
      considered in remission still showed an ACTH increase after desmopressin and, on
      the contrary, four patients with disappearance of the ACTH response had
      persistence of hypercortisolism. During follow-up monitoring, three patients, who
      had persistence of the ACTH response to desmopressin, relapsed 24, 38 and 54
      months after surgery. CONCLUSIONS: Desmopressin administration elicits a
      significant rise in ACTH and cortisol levels in the majority but not all patients
      with Cushing's disease. There is a good, but not complete, concordance between
      the response to the desmopressin test and the surgical outcome. Our preliminary
      data show that persistence of the ACTH response to desmopressin in the early
      postoperative period might be associated with a higher risk of late relapse.

PMID- 11453954
TI  - The atherogenic plasma remnant-like particle cholesterol concentration is
      increased in the fasting and postprandial state in active acromegalic patients.
AB  - BACKGROUND: Premature atherosclerosis is a clinical feature in untreated
      acromegaly. Increased postprandial lipoprotein remnant levels are associated with
      premature atherosclerosis. In most studies, remnants have been measured
      indirectly using retinyl esters (RE) as a chylomicron core label. Remnants can
      also be directly quantified by immunoseparation using monoclonal antibodies to
      apolipoprotein (apo) AI and apo B100 to remove nonremnant lipoproteins.
      Cholesterol is quantified in the remaining apo E-rich remnant fraction (RLP-C).
      OBJECTIVE: The aim of the present study was to investigate the role of
      postprandial lipaemia in patients with acromegaly to further define abnormalities
      leading to increased susceptibility for atherosclerosis. PATIENTS: In a case
      control study, the plasma postprandial lipoprotein remnant fraction (RLP-C and
      RE) were analysed in six patients with active acromegaly [two females, four
      males; aged 53 +/- 9 years; body mass index (BMI), 29 +/- 4 kg/m2] and in six
      normolipidaemic control subjects (matched for age, gender, BMI and apo E
      genotype). They underwent an oral vitamin A fat loading test. RESULTS: Baseline
      plasma triglycerides (TG) were not significantly different in patients (1.75 +/-
      0.71 mM) and controls (1.15 +/- 0.46 mM). Lipoprotein lipase activity was
      significantly lower in patients than in controls (108 +/- 21 vs. 141 +/- 19 U/l,
      respectively; P < 0.05). Baseline plasma apo E levels were higher in patients
      (60.8 +/- 7.9 mg/l) than in controls (48.3 +/- 5.9 mg/l; P < 0.05). No
      differences were found in the area under the postprandial TG curve (AUC-TG), the
      incremental AUC-TG (DeltaAUC-TG) and AUC-RE in the Sf < 1000 remnant fraction.
      However, fasting plasma RLP-C concentrations, isolated by immunoseparation, were
      increased in patients with active acromegaly (0.41 +/- 0.13 mM) compared to
      control subjects (0.20 +/- 0.07 mM; P < 0.05). Incremental postprandial RLP-C
      response (corrected for fasting values) was also significantly elevated in
      patients (2.14 +/- 1.19 mM/h/l) compared to controls (0.86 +/- 0.34 mM/h/l; P <
      0.05). In both groups, the maximal RLP-C concentration was reached between 2 and
      4 h. CONCLUSIONS: In conclusion, the atherogenic postprandial remnants,
      represented by RLP-C, were significantly elevated at baseline and in the
      postprandial period, whereas the larger-sized remnants, represented by retinyl
      esters (Sf < 1000), were not different from controls. The disturbances in the
      postprandial RLP-C response increased the susceptibility for premature
      atherosclerosis as observed in patients with acromegaly.

PMID- 11453955
TI  - GH administration and discontinuation in healthy elderly men: effects on body
      composition, GH-related serum markers, resting heart rate and resting oxygen
      uptake.
AB  - BACKGROUND AND OBJECTIVES: GH administration results in increased lean body mass
      (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy
      may therefore have potential benefits, especially in the elderly, who are known
      to have decreased function of the GH/IGF-I axis. Several studies have focused on
      effects of GH administration in the elderly in the last decade. However, very
      limited information is available regarding changes in body composition and EE
      upon GH discontinuation in the elderly. The present study therefore investigated
      the effects of 12 weeks of GH administration and subsequent discontinuation on
      body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH
      related serum markers in healthy elderly men. SUBJECTS AND METHODS: Sixteen
      healthy men [age 74 +/- 1 years (mean +/- SEM), height 174.2 +/- 1.6 cm, body
      weight 80.7 +/- 2.6 kg, body fat 27.5 +/- 1.1%] completed the study protocol.
      Recombinant human GH (1.80 +/- 0.24 IU/day) was administered for 12 weeks in a
      single-blinded, placebo-controlled design. Body composition (dual energy X-ray
      absorptiometry), resting VO2 (indirect calorimetry), resting HR (telemetry) and
      serum IGF-I, IGF-II, IGFBP-3 and acid labile subunit (ALS) were measured at
      baseline, after 12 weeks of GH administration and, additionally in the GH group,
      1, 2, 3, 4, 5 and 9 days after GH discontinuation. RESULTS: Body weight was
      unchanged from baseline to 12 weeks in both groups. However, GH administration
      caused a decrease in FM (3.4 +/- 1.0 kg, P < 0.012), paralleled by a similar
      increase in LBM (3.2 +/- 0.4 kg, P < 0.0002). Resting VO2 and resting HR
      increased by 31 +/- 3.6% and 7.3 +/- 1.9 per minute, respectively, in the GH
      group, where significant increases in serum IGF-I, IGFBP-3 and ALS also were
      noted. None of the above parameters changed in the placebo group. Within 2-3 days
      after GH discontinuation, the GH related serum markers and resting HR returned to
      baseline levels, whereas resting VO2 remained elevated even 9 days after GH
      discontinuation. In addition, GH discontinuation caused a significant decrease in
      body weight (1.86 +/- 0.35 kg), derived exclusively from a decrease in LBM (1.63
      +/- 0.43 kg), while the decreased FM was maintained (12 weeks: 17.93 +/- 1.65 kg,
      +9 days: 17.74 +/- 1.62 kg). CONCLUSIONS: The increases in serum IGF-I, IGFBP-3,
      ALS and resting heart rate induced by 12 weeks of GH administration in elderly
      men returned to baseline levels within 2-3 days after GH discontinuation.
      However, resting VO2 remained elevated for a longer period. GH administration
      reduced fat mass but maintained body weight by increasing lean body mass. In
      contrast, 9 days of GH discontinuation reduced body weight exclusively by
      reducing lean body mass.

PMID- 11453956
TI  - Increased insulin sensitivity in young, growth hormone deficient children.
AB  - OBJECTIVE: Although growth hormone (GH) has well documented insulin antagonistic
      effects, GH deficient adults often demonstrate insulin resistance. In young GH
      deficient children, increased susceptibility to hypoglycaemia might indicate
      increased insulin sensitivity; however, this has not been documented. We
      therefore determined insulin sensitivity in GH deficient and GH sufficient
      children. DESIGN AND PATIENTS: Prospective study of children undergoing insulin
      tolerance tests for clinical investigation of GH or cortisol secretion at a
      regional Paediatric Endocrine/Growth Clinic between October 1986 and December
      1997. Ninety-one tests were performed in children with GH deficiency and 142
      tests in children with normal GH response to insulin (peak GH > or = 20 IU/l).
      MEASUREMENTS: The standard insulin tolerance test was modified to permit frequent
      measurements of glucose (0, 5, 10, 15, 20, 30, 45, 60 and 90 minutes). Rate of
      log glucose disappearance in the first 15 minutes was calculated as a direct
      measure of insulin sensitivity. RESULTS: GH deficient children were more insulin
      sensitive than GH sufficient children (P = 0.004) and had lower glucose nadirs
      post-insulin (P = 0.005). Subgroup analysis revealed that these differences were
      greater in younger (< 12 years old) or pre/early pubertal children. In 14
      prepubertal children, exogenous sex steroid priming resulted in lower insulin
      sensitivity (P < 0.05) compared to nonprimed tests. CONCLUSIONS: Young GH
      deficient children were more insulin sensitive than children with normal GH
      secretion. This difference attenuated with age and puberty, possibly secondary to
      pubertal sex steroids; however, insulin resistance as reported in GH deficient
      adults, was not observed in adolescents.

PMID- 11453957
TI  - Effects of 6 years of growth hormone (GH) treatment on bone mineral density in GH
      deficient adults.
AB  - OBJECTIVE: Adults with growth hormone (GH) deficiency are often osteopenic. Short
      term GH replacement therapy has been shown to improve bone mineral density (BMD).
      However, whether the increases in BMD are progressive with time is still unclear.
      We therefore examined long-term changes in BMD with GH treatment in GH-deficient
      adults over a period of 6 years. DESIGN: Open prospective GH therapeutic study.
      PATIENTS: Twelve GH-deficient patients (four women, eight men) with a mean age of
      42.5 years (range 24-61 years) at the beginning of GH replacement. Eleven
      patients suffered in addition from LH/FSH insufficiency, eight from TSH
      insufficiency and eight from ACTH insufficiency. Before the start of GH
      substitution, the insufficient anterior pituitary axes were fully substituted for
      an average of 9.8 years (range 2-22 years). Average daily GH dose was 2.4 IU (SD
      0.86). MEASUREMENTS: BMD and bone area were measured at annual intervals at the
      lumbar spine and at the proximal femur using dual-X-ray absorptiometry. RESULTS:
      Under GH substitution, serum insulin-like growth factor I concentrations
      increased by 140 microg/l compared to pretherapeutic values (P = 0.0003). BMD at
      the lumbar spine increased by 0.16 g/cm2 (P = 0.0005), corresponding to a mean
      increase of 15.9% or an increase of the BMD Z-score by 1.53 SD. Increases in BMD
      were independently observed from years 3 to 6 by a mean of 5.8% (P = 0.0087).
      This increase was paralleled by an increase in the area of the lumbar vertebrae.
      Bone area also increased at selected sites of the proximal femur, but there was
      no consistent increase in BMD at the proximal femur. CONCLUSION: GH therapy in GH
      deficient adults is able to progressively increase BMD and bone area at the
      lumbar spine over a period of at least 6 years. However, our study has several
      limitations, making it necessary to confirm these findings in further long-term
      studies.

PMID- 11453958
TI  - Low serum concentrations of insulin-like growth factor I are associated with
      femoral bone loss in a population-based sample of postmenopausal women.
AB  - OBJECTIVE: Cross-sectional studies suggest that the decline in insulin-like
      growth factor-I (IGF-1) levels with age may contribute to age-associated bone
      loss. However, prospective data on the relation between circulating IGF-I and
      bone loss in old age have not yet been reported. DESIGN: A longitudinal study
      (follow-up time 3.3 years) of the change of bone mineral density (BMD) at the
      lumbar spine and femoral neck in relation to serum IGF-I. PATIENTS: A population
      based sample of 173 elderly men and 107 postmenopausal women without medical
      conditions or medication known to significantly affect BMD or serum IGF-I levels.
      MEASUREMENTS: BMD at the lumbar spine and femoral neck at baseline and after a
      mean follow-up-time of 3.3 years, serum-IGF-I, insulin-like growth factor binding
      protein 3 (IGFBP-3), sex hormone-binding globulin (SHBG) and biologically
      available testosterone (BAT). RESULTS: In women, there was a graded negative
      relationship between quartiles of serum IGF-I and bone loss at the proximal femur
      (P = 0.04), which persisted after adjustment for potential covariables of bone
      loss and serum IGF-I. In subgroup analysis the association between serum IGF-I
      and change in BMD was only apparent in women more than 10 years past menopause (r
      = + 0,38, P = 0.01). No association between serum IGF-I levels and changes in BMD
      was observed in men. IGF-I levels were not associated with changes in spinal BMD.
      CONCLUSIONS: Our data suggest that low circulating levels of IGF-I in elderly
      women are associated with greater femoral bone loss, and support previous
      findings of gender differences in the relation between serum IGF-I and BMD in
      older age.

PMID- 11453959
TI  - Treatment with insulin lispro changes the insulin profile but does not affect the
      plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes.
AB  - OBJECTIVE: IGF-I levels in patients with type 1 diabetes without endogenous
      insulin production are low. Our aim was to examine whether the plasma insulin
      profile obtained by treatment with the insulin analogue lispro has a different
      effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during
      treatment with conventional human insulin (regular insulin). DESIGN AND PATIENTS:
      Twelve patients with type 1 diabetes, age 47.8 +/- 2.4 years (mean +/- SEM), body
      mass index 26.5 +/- 1.0 kg/m2, diabetes duration 30.5 +/- 3.2 years participated
      in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were
      measured at the end of 6 weeks treatment with each insulin being administered by
      a continuous subcutaneous insulin infusion. IGF-I was measured fasting while
      IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly
      after a morning meal preceded by an insulin bolus dose. RESULTS: Lispro gave a
      marked insulin peak of 135 +/- 20 pmol/l 50 minutes after injection. After an
      initial rapid rise, human regular insulin reached a plateau of approximately 50
      pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h
      was more than twice as large on lispro as on regular insulin (P = 0.01). Plasma
      IGF-I concentration was 78.8 +/- 10.9 microg/l on lispro and 82.3 +/- 10.5
      microg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show
      a significant difference even when divided from 0710 h to 0910 h and from 0930 h
      to 1430 h. Blood glucose AUC after administration of the bolus was significantly
      lower during treatment with lispro (P = 0.006) but glycosylated haemoglobin
      (HbA1c) was 6.4 +/- 0.2% on both therapies. CONCLUSIONS: Our results indicate
      that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes
      does not differ from that of human regular insulin.

PMID- 11453960
TI  - Plasma leptin in chronic fatigue syndrome and a placebo-controlled study of the
      effects of low-dose hydrocortisone on leptin secretion.
AB  - OBJECTIVE: Previous studies have suggested that chronic fatigue syndrome (CFS) is
      associated with changes in appetite and weight, and also with mild
      hypocortisolism. Because both of these features may be related to leptin
      metabolism, we undertook a study of leptin in CFS. DESIGN: (i) A comparison of
      morning leptin concentration in patients with CFS and controls and (ii) a
      randomized, placebo-controlled crossover study of the effects of hydrocortisone
      on leptin levels in CFS. PATIENTS: Thirty-two medication free patients with CFS
      but not comorbid depression or anxiety. Thirty-two age, gender, weight, body mass
      index and menstrual cycle matched volunteer subjects acted as controls.
      MEASUREMENTS: We measured basal 0900 h plasma leptin levels in patients and
      controls. All 32 patients were taking part in a randomized, placebo-controlled
      crossover trial of low dose (5 or 10 mg) hydrocortisone as a potential therapy
      for CFS. We measured plasma leptin after 28 days treatment with hydrocortisone
      and after 28 days treatment with placebo. RESULTS: At baseline, there was no
      significant difference in plasma leptin between patients [mean 13.8, median 7.4,
      interquartile range (IQR) 18.0 ng/ml] and controls (mean 10.2, median 5.5, IQR
      11.3 ng/ml). Hydrocortisone treatment, for both doses combined, caused a
      significant increase in leptin levels compared to placebo. When the two doses
      were analysed separately, only 10 mg was associated with a significant effect on
      leptin levels. We also compared the hydrocortisone induced increase in leptin
      between those who were deemed treatment-responders and those deemed
      nonresponders. Responders showed a significantly greater hydrocortisone-induced
      rise in leptin than nonresponders. This association between a clinical response
      to hydrocortisone and a greater rise in leptin levels may indicate a greater
      biological effect of hydrocortisone in these subjects, perhaps due to increased
      glucocorticoid receptor sensitivity, which may be present in some patients with
      CFS. CONCLUSIONS: We conclude that, while we found no evidence of alterations in
      leptin levels in CFS, low dose hydrocortisone therapy caused increases in plasma
      leptin levels, with this biological response being more marked in those CFS
      subjects who showed a positive therapeutic response to hydrocortisone therapy.
      Increases in plasma leptin levels following low dose hydrocortisone therapy may
      be a marker of pretreatment physiological hypocortisolism and of response to
      therapy.

PMID- 11453961
TI  - Gonadotrophin releasing hormone agonist treatment with or without recombinant
      human GH in adopted children with early puberty.
AB  - BACKGROUND: Early onset of puberty is frequently observed in adopted children.
      During treatment with a gonadotrophin releasing hormone agonist (GnRHa), a
      decrease in height velocity (HV) precludes height gain. OBJECTIVE AND DESIGN: We
      studied the effect of the addition of GH to GnRHa treatment in a 3-year
      prospective randomized trial in 30 adopted children with early puberty. PATIENTS:
      Mean age (SD) at start of treatment was 9.6 (0.9) years in girls and predicted
      adult height (PAH) using a segmented bone age (BA) assessment method was 148.0
      (5.3) cm. RESULTS: HV decreased gradually in both groups with a higher HV in the
      group with GH addition (group B). No significant difference between the rates of
      bone maturation [change in bone age (DeltaBA)/change in chronological age
      (DeltaCA)] of both treatment groups was observed. After 3 years of treatment, PAH
      increase was 5.7 (3.8) cm in group A (GnRHa alone) and 10.1 (3.8) cm in group B
      (P < 0.01). IGF-I levels were higher in group B. HV decreased slowly in both
      groups during treatment, unlike stabilization of IGF-I levels. CONCLUSION: We
      conclude that, after 3 years of treatment, the addition of GH to GnRHa results in
      higher HV and a significant increase in PAH compared to GnRHa alone.

PMID- 11453962
TI  - A chimeric CYP11B1/CYP11B2 gene in glucocorticoid-insuppressible familial
      hyperaldosteronism.
AB  - Although a chimeric gene combining the 11beta-hydroxylase gene (CYP11B1) and the
      aldosterone synthase gene (CYP11B2) explains the pathophysiology of familial
      hyperaldosteronism (FH) type I, the contribution of this abnormality to FH type
      II has not been tested. We screened genomic DNA from a Japanese family with FH
      type II for the CYP11B1/CYP11B2 gene. The index patient was a 27-year-old woman
      with hypertension. Hypokalaemia, elevated plasma aldosterone and suppressed
      plasma renin activity suggested primary aldosteronism. Though computed tomography
      failed to reveal an adrenal tumour, left adrenalectomy was indicated due to a
      high aldosterone concentration in left adrenal venous blood. The resected adrenal
      gland contained an adenoma. As her mother had also been diagnosed with primary
      aldosteronism due to an adenoma, we administered oral dexamethasone to our
      patient before the operation and observed the response of the blood pressure and
      plasma aldosterone concentration for 2 weeks. Both parameters remained elevated
      during the treatment period, confirming the diagnosis of FH type II. Total DNA
      was isolated from blood cells of the index patient, her mother, and an unaffected
      brother. Samples were amplified by polymerase chain reaction using specific
      primers from CYP11B1 and CYP11B2. Unique DNA fragments of 1.4 kb were obtained
      from the index patient and her mother, but not from the healthy subject. The
      CYP11B1/CYP11B2 chimeric gene was found in a Japanese family with FH type II.

PMID- 11453963
TI  - Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) isoform
      expression in ectopic acromegaly.
AB  - Bronchial endocrine neoplasms causing acromegaly due to ectopic production of
      growth hormone (GH)-releasing hormone (GHRH) have been reported. We describe the
      case of a 39-year-old man with clinical and biochemical acromegaly. Magnetic
      resonance imaging revealed an enlarged pituitary, which was confirmed
      histologically to harbour somatotroph hyperplasia. Further investigations
      identified a circumscribed central mass in the right lung which was surgically
      resected and histologically confirmed to be an endocrine tumour with strong
      immunopositivity for GHRH, synaptophysin and chromogranin; the lesion also
      exhibited mild positivity for peptide YY, calcitonin gene-related peptide (CGRP),
      glucagon-like peptide (GLP)-1, corticotrophin-releasing hormone (CRH), tyrosine
      hydroxylase, vasoactive intestinal peptide (VIP) and enkephalin. S100 protein was
      identified in stellate cells surrounding nests of epithelial tumour cells. The
      MIB-1 antibody labelled about 10% of the tumour cells. We established that the
      tumour not only produced GHRH but the GHRH-receptor (GHRH-R) as well. GHRH and
      GHRH-R mRNA were identified and the latter was characterized as two variants, a
      full-length transcript and a truncated splice variant that has been described in
      human pituitary somatotroph adenomas. We suggest that GHRH expression by this
      tumour and the presence of its receptor may be responsible for enhanced growth.
      The expression of a truncated splice variant that is unable to transduce GHRH
      signalling may be implicated in the less aggressive behaviour of well
      differentiated endocrine tumours that produce GHRH compared with small-cell lung
      carcinomas that are very responsive to GHRH growth stimulation.

PMID- 11453964
TI  - The Smith-Lemli-Opitz syndrome: a novel metabolic way of understanding
      developmental biology, embryogenesis, and dysmorphology.
AB  - The brief history of the Smith-Lemli-Opitz syndrome (SLOS) (MIM 270400) reflects
      that of latter 20th century dysmorphology and biochemical and molecular genetics:
      from its first description as a rare but characteristic multiple malformation
      syndrome known only to a handful of dysmorphologists, to a relatively common
      Garrodian defect with a complex molecular basis that has captured the attention
      of researchers and basic scientists from the fields as diverse as embryology,
      developmental biology, sterol biochemistry, epidemiology, and teratology. The
      discovery of the underlying biochemical defect - deficiency of 3beta
      hydroxysteroid-Delta7-reductase (DHCR7), an enzyme catalyzing the last step of
      cholesterol biosynthesis, and the resultant generalized cholesterol deficiency -
      has led to an explosion of knowledge of this biochemical pathway and to a
      paradigm shift in the recognition of metabolic deficiencies as causes of
      dysmorphic syndromes. Characterization of the human DHCR7 gene and the
      identification of mutations in patients with SLOS have revealed a complex picture
      of molecular heterogeneity and provided insights into the structure and function
      of DHCR7. SLOS is the first metabolic malformation syndrome with profound effects
      on the body plan, and its discovery has paved the way to the discovery of a
      number of other defects of the cholesterol synthetic pathway.

PMID- 11453970
TI  - Genetic landmarks through philately: the Human Genome Project and the new
      millennium.

PMID- 11453971
TI  - LDL-receptor gene mutations and the hypocholesterolemic response to statin
      therapy.
AB  - Studies of the cholesterol lowering effect of statin therapy as a function of low
      density lipoprotein (LDL)-receptor mutation type have not produced a clear
      picture, possibly because they included patients with several different kinds of
      LDL-receptor mutations. We studied the response to treatment with fluvastatin in
      28 patients with heterozygous familial hypercholesterolemia as a result of a
      receptor-negative mutation (Trp23-stop) and in 30 patients with a receptor
      binding defective mutation (Trp66-Gly) to test the hypothesis that response to
      treatment depends on the type of mutation. Patients were randomized to 12 weeks
      of treatment with fluvastatin 40 mg daily and 12 weeks of placebo treatment,
      preceded by a placebo run-in period of 8 weeks in a double-blind, cross-over
      design. Untreated plasma concentrations of lipids and lipoproteins were similar
      in the two groups of patients. Plasma cholesterol and LDL cholesterol response to
      therapy tended to be less marked in receptor-binding defective patients, but the
      differences were not statistically significant. A tabulation of the results of
      the present and earlier studies suggests that differences in treatment response
      as an apparent function of LDL-receptor gene mutational type occur mainly in
      populations with recent genetic admixture (<400 years). In such populations,
      persons with the same mutation in the LDL-receptor gene are more likely to share
      other but undetermined genetic variations affecting the pharmacology of statins.

PMID- 11453972
TI  - Rett syndrome from quintuple and triple deletions within the MECP2 deletion
      hotspot region.
AB  - Rett syndrome results from mutations in the X-linked methyl-CpG-binding protein 2
      (MECP2) gene, which are nearly always lethal in males and lead to regression and
      reduced life expectancy in females. Herein we report one propositus with five
      tandem deletions and a second propositus with three tandem deletions within MECP2
      exon 4 that encode truncated protein products resulting in classic Rett syndrome.
      These deletion breakpoints and single deletions in 3 other patients were all
      found within a 185-bp region along with 64 of 69 other reported deletion
      breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion
      at a substantial proportion of the shared MECP2 sites is enhanced by repeated
      guanosine (G) DNA sequences in the antisense direction, consistent with reports
      at other gene loci that polypurine (multiple guanosine or adenosine (A))
      basepairs enhance sequence deletion. Multiple deletions at the same poly G
      recombination sites confirm the existence of deletion hotspots in this gene
      region with numerous repeated antisense sites that are enriched 26- to 161-fold.
      Deletion by illegitimate recombination within a single allele can occur during
      mitotic or meiotic cell cycles. Although prone to disease-causing deletion, this
      region is unique in humans and highly conserved among mammals for the last 75 000
      000 years to maintain the MECP2 gene's critical function.

PMID- 11453973
TI  - Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian
      women with breast cancer.
AB  - The frequency of BRCA1 and BRCA2 mutations in women with breast cancer varies
      according to the age at diagnosis, family history of cancer, and
      ethnicity/country of origin. We set out to estimate the frequency of seven
      previously described founder mutations in BRCA1 and BRCA2 in all eligible French
      Canadian women diagnosed with invasive breast cancer at one Montreal hospital
      over a 20-month period. One hundred and ninety-two patients were eligible and 127
      (66.2%) provided blood for genetic testing. We identified 4 women who carried a
      founder mutation (3.1%, 95% confidence interval 0.9-7.9%) in this population.
      Interestingly, all the mutations were in BRCA2. The mean age at diagnosis for
      mutation carriers was 51.2 years (range 49.1-53.5). Two of these 4 cases were
      lobular invasive carcinomas and 2 were ductal carcinomas, histological grade 1 or
      2. Despite a small tumor size (< or =20 mm), axillary nodal involvement was
      present in 3 women. Estrogen receptors were strongly expressed in all cases. Two
      of the 4 cases reported a strong family history of breast cancer, but a family
      history of site-specific breast cancer was a relatively poor indicator of the
      presence of BRCA2 mutations. The absence of BRCA1 mutations may be a result of
      chance, but may also reflect different geographical origins of the most common
      BRCA1 mutations within the French Canadian population.

PMID- 11453974
TI  - Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q
      mutation in RLBP1.
AB  - Fundus albipunctatus (FA; OMIM 136880) is a rare form of apparently stationary
      night blindness characterized by the presence of myriad symmetrical round white
      dots in the fundus with a greater concentration in the midperiphery. A distantly
      similar but distinct clinical entity, retinitis punctata albescens (RPA), is also
      characterized by aggregation of irregular white flecks but is progressive and
      evolves to generalized atrophy of the retina. We studied 4 consanguineous
      kindreds diagnosed with FA from Saudi Arabia. Given the substantial phenotypic
      variation and overlap between different flecked retinal dystrophies, we evaluated
      all known genes associated with such conditions by both genetic analysis and
      direct sequencing. In one kindred, KKESH-099, we identified a homozygous R150Q
      alteration in RLBP1, the gene encoding the cellular retinaldehyde binding
      protein, associated previously with both recessive retinitis pigmentosa (arRP)
      and RPA. Examination of several patients aged 3-20 years over a 9-year period
      presented no evidence for either RP or RPA. In contrast, clinical examination of
      individuals with the same mutation in their fourth and fifth decade revealed
      signs consistent with RPA. The data suggest that the R150Q mutation in RLBP1 may
      result in RPA with slow progression. More importantly, younger individuals
      diagnosed with the milder disorder FA thought to be stationary may evolve to a
      more devastating and progressive phenotype.

PMID- 11453975
TI  - Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient.
AB  - Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive
      disease, which presents clinically as severe combined immunodeficiency (SCID). We
      report here two novel mutations in the PNP gene that result in SCID phenotype, in
      a single patient. The maternal-derived allele carries a C to T transition in exon
      2 resulting in a premature stop codon at amino acid 57. The paternal-derived
      mutation is a G to A transition at position +1 in intron 3, causing a complete
      skipping of exon 3 and a reading frameshift at the exon 2-exon 4 junction. The
      predicted polypeptide encoded by the aberrantly spliced mRNA terminates
      prematurely after only 89 amino acids. Both mutations predict severely truncated
      proteins resulting in a complete deficiency of PNP enzymatic activity, yet the
      development of profound immunodeficiency in this patient is greatly delayed.

PMID- 11453976
TI  - Cryptic duplication of 21q in an individual with a clinical diagnosis of Down
      syndrome.
AB  - We describe an adult male who was diagnosed with Down syndrome (DS) at 9 months
      of age, but had repeatedly normal karyotypes until recent mid-resolution
      chromosome studies showed a possible duplication of 21q22.13 to 21q22.3. The
      abnormality was investigated using fluorescent in situ hybridization (FISH)
      studies. These showed hybridization of a whole chromosome paint probe (wcp21,
      Oncor Coatasome 21) to the entire length of both chromosome 21 homologues and one
      very large hybridization signal of a cosmid contig probe localized within bands
      21q22.13-21q22.2(LSI-21, Vysis) on the ?dup(21q) homologue. CGH analysis
      identified a ratio of 1.5 for the segment of chromosome 21 involving band 21q22,
      indicating a gain of part, or all, of the terminal band of chromosome 21. The
      karyotype was thus defined as 46,XY,?dup(21) (q22.13q22.2).ish dup(21)(LSI
      21++,wcp21+). Common DS characteristics in our case and 12 previously reported
      cases with duplications involving chromosome 21 included mental retardation,
      fifth finger clinodactyly, open mouth and oblique eye fissures. Transverse palmar
      creases and congenital heart defects, seen in DS less than 40% of the time, were
      infrequent. Presence of these features did not appear to depend on the specific
      portion of chromosome 21 that was duplicated. A review of 18 additional clinical
      features showed no consistent phenotype-genotype correlations.

PMID- 11453977
TI  - Fibrillin-1 (FBN1) gene frameshift mutations in Marfan patients: genotype
      phenotype correlation.
AB  - Marfan syndrome (MFS) is a multisystemic disease associated with mutations in the
      fibrillin-1 gene. Most of the reported mutations are missense substitutions
      mainly affecting the epidermal growth factor (EGF)-like protein domain structure
      and the calcium-binding (cb) site. The aim of our study was to investigate the
      correlation between fibrillin-1 frameshift mutations and the clinical phenotype
      in patients affected by MFS. In 48 out of 66 Marfan patients a pathogenetic
      mutation was found. We detected novel mutations causing premature termination
      codon in exons 19, 37, 40 and 41 of four Italian patients. The first mutation in
      exon 19 (cbEGF #8 domain) results in a clinical phenotype involving mainly the
      skeletal and cardiovascular systems. Interestingly, we noticed that, while
      mutations in exons 37 and 41 (eight cysteine domains #4 and #5) are milder, the
      mutation in exon 40 (cbEGF #24 domain) is more severe and causes major
      cardiovascular involvement with thoracic and abdominal aortic aneurysms. It is
      noteworthy that the degree of the severity in the phenotype of one of our
      patients and another from the literature carrying a mutation in exon 41 could be
      explained with alterations in mRNA expression.

PMID- 11453978
TI  - Antley-Bixler syndrome and maternal virilization: a proposal of genetic
      heterogeneity.

PMID- 11453979
TI  - Roles of homocysteine in cell metabolism: old and new functions.
AB  - Mild hyperhomocysteinemia has been suggested as a new, independent risk factor
      for cardiovascular disease. This fact has produced a new, increased interest in
      the study of homocysteine metabolism and its relation to pathogenesis. This
      emergent area of biomedical research is reviewed here, stressing the biochemical
      and metabolic basis of the pathogenicity of increased levels of homocysteine.

PMID- 11453980
TI  - Biochemical characterization of nuclear pore complex protein gp210 oligomers.
AB  - The membrane-spanning glycoprotein gp210 is a major component of the nuclear pore
      complex. This nucleoporin contains a large cisternal N-terminal domain, a short C
      terminal cytoplasmic tail, and a single transmembrane segment. We show here that
      dimers of native gp210 can be isolated from cell extracts by immunoprecipitation,
      and from purified rat liver nuclear envelopes by velocity sedimentation and gel
      filtration. Cross-linking of proteins in isolated membranes prior to
      solubilization dramatically increases the proportion of dimers. The dimers are
      SDS-resistant, as previously observed for some integral membrane proteins of cis
      Golgi and plasma membrane proteins, including glycophorin A. Larger oligomers of
      gp210 can also be obtained by gel filtration and denaturing electrophoresis, but
      unlike the dimers are dissociated by reduction and heating in the presence of
      SDS. We propose that gp210 is organized into the pore membrane as a large array
      of gp210 dimers that may constitute a luminal submembranous protein skeleton.

PMID- 11453981
TI  - Secretory ribonucleases in the primitive ruminant chevrotain (Tragulus
      javanicus).
AB  - Phylogenetic analyses of secretory ribonucleases or RNases 1 have shown that gene
      duplication events, giving rise to three paralogous genes (pancreatic, seminal
      and brain RNase), occurred during the evolution of ancestral ruminants. A higher
      number of paralogous sequences are present in chevrotain (Tragulus javanicus),
      the earliest diverged taxon within the ruminants. Two pancreatic RNase sequences
      were identified, one encoding the pancreatic enzyme, the other encoding a
      pseudogene. The identity of the pancreatic enzyme was confirmed by isolation of
      the protein and N-terminal sequence analysis. It is the most acidic pancreatic
      ribonuclease identified so far. Formation of the mature enzyme requires cleavage
      by signal peptidase of a peptide bond between two glutamic acid residues. The
      seminal-type RNase gene shows features of a pseudogene, like orthologous genes in
      other ruminants investigated with the exception of the bovine species. The brain
      type RNase gene of chevrotain is expressed in brain tissue. A hybrid gene with a
      pancreatic-type N-terminal and a brain-type C-terminal sequence has been
      identified but nothing is known about its expression. Phylogenetic analysis of
      RNase 1 sequences of six ruminant, three other artiodactyl and two whale species
      support previous findings that two gene duplications occurred in a ruminant
      ancestor. Three distinct groups of pancreatic, seminal-type and brain-type RNases
      have been identified and within each group the chevrotain sequence it the first
      to diverge. In taxa with duplications of the RNase gene (ruminants and camels)
      the gene evolved at twice as fast than in taxa in which only one gene could be
      demonstrated; in ruminants there was an approximately fourfold increase directly
      after the duplications and then a slowing in evolutionary rate.

PMID- 11453982
TI  - Co-clustering of Fcgamma and B cell receptors induces dephosphorylation of the
      Grb2-associated binder 1 docking protein.
AB  - The immunoreceptor tyrosine-based inhibitory motif (ITIM) of human type IIb
      Fcgamma receptor (FcgammaRIIb) is phosphorylated on its tyrosine upon co
      clustering with the B cell receptor (BCR). The phosphorylated ITIM (p-ITIM) binds
      to the SH2 domains of polyphosphoinositol 5-phosphatase (SHIP) and the tyrosine
      phosphatase, SHP-2. We investigated the involvement of the molecular complex
      composed of the phosphorylated SHIP and FcgammaRIIb in the activation of SHP-2.
      As a model compound, we synthesized a bisphosphopeptide, combining the sequences
      of p-ITIM and the N-terminal tyrosine phosphorylated motif of SHIP with a
      flexible spacer. This compound bound to the recombinant SH2 domains of SHP-2 with
      high affinity and activated the phosphatase in an in vitro assay. These data
      suggest that the phosphorylated FcgammaRII-SHIP complexes formed in the intact
      cells may also activate SHP-2. Grb2-associated binder 1 (Gab1) is a multisite
      docking protein, which becomes tyrosine-phosphorylated in response to various
      types of signaling, including BCR. In turn it binds to the SH2 domains of SHP-2,
      SHIP and the p85 subunit of phosphatidyl inositol 3-kinase (PtdIns3-K) and may
      regulate their activity. Gab1 is a potential substrate of SHP-2, thus its binding
      to FcgammaRIIb may modify the Gab1-bound signaling complex. We show here that
      Gab1 is part of the multiprotein complex assembled by FcgammaRIIb upon its co
      clustering with BCR. Gab1 may recruit SH2 domain-containing molecules to the
      phosphorylated FcgammaRIIb. SHP-2, activated upon the binding to FcgammaRIIb-SHIP
      complex, partially dephosphorylates Gab1, resulting in the release of PtdIns3-K
      and ultimately in the inhibition of downstream activation pathways in
      BCR/FcgammaRIIb co-aggregated cells.

PMID- 11453983
TI  - Concurrent maltodextrin and cellodextrin synthesis by Fibrobacter succinogenes
      S85 as identified by 2D NMR spectroscopy.
AB  - 1D and 2D NMR experiments were used to analyse the synthesis of various
      metabolites by resting cells of Fibrobacter succinogenes S85 when incubated with
      [1-(13)C]glucose, in both extracellular and cellular media. Besides the expected
      glycogen, succinate, acetate, glucose-1-P and glucose-6-P, maltodextrins and
      cellodextrins were detected. Maltodextrins were excreted into the external
      medium. They were found to have linear structures with a maximum degree of
      polymerization (DP) of about 6 or 7 units. Cellodextrins were located in the
      cells (cytoplasm and/or periplasm), and their DP was < or = 4. Both labelled (1
      (13)C and 6-(13)C) and unlabelled maltodextrins and cellodextrins were detected,
      showing the contribution of carbohydrate cycling in F. succinogenes, including
      the reversal of glycolysis and the futile cycle of glycogen. The mechanisms of
      these oligosaccharide syntheses are discussed.

PMID- 11453984
TI  - Transcriptionally and post-transcriptionally regulated response of 13 calmodulin
      genes to tobacco mosaic virus-induced cell death and wounding in tobacco plant.
AB  - We isolated 13 tobacco calmodulin (CaM) genes, NtCaM1-13, and analyzed their
      expression profile in response to pathogen infection and wounding using specific
      DNA probes for individual CaM genes and specific antibodies for CaM proteins in
      groups I (NtCaM1/2), II (NtCaM3/4/5/6/7/8/11/12 and 9/10) and III (NtCaM13),
      respectively. Synchronous cell death in tobacco mosaic virus (TMV)-infected N
      gene-containing tobacco leaves accompanied a predominant accumulation of NtCaM1,
      2 and 13 transcripts and NtCaM13-type protein, which is a possible ortholog of
      soybean defense-involved CaM (SCaM-4), preceding induction of PR-1 and PR-3
      defense genes. Accumulation of NtCaM1, 2, 3 and 4 transcripts was induced within
      30 min after wounding and NtCaM1-type protein accumulated transiently after
      wounding. NtCaM13-type protein, which was found at a low level in healthy leaves,
      decreased instantly after wounding. The treatment with a proteasome inhibitor,
      lactacystin, enhanced wound-induced accumulation of NtCaM1-type protein and
      inhibited wound-induced decrease of NtCaM13-type protein, suggesting that
      proteasome activity is involved in the degradation of these CaMs. Thus, our
      results indicate that levels of individual CaM proteins are differentially
      regulated both transcriptionally and post-transcriptionally in tobacco plants
      that are exposed to stresses such as pathogen-induced hypersensitive cell death
      and wounding.

PMID- 11453985
TI  - In situ kinetic analysis of glyoxalase I and glyoxalase II in Saccharomyces
      cerevisiae.
AB  - The kinetics of glyoxalase I [(R)-S-lactoylglutathione methylglyoxal-lyase; EC
      4.4.1.5] and glyoxalase II (S-2-hydroxyacylglutathione hydrolase; EC 3.1.2.6)
      from Saccharomyces cerevisiae was studied in situ, in digitonin permeabilized
      cells, using two different approaches: initial rate analysis and progress curves
      analysis. Initial rate analysis was performed by hyperbolic regression of initial
      rates using the program HYPERFIT. Glyoxalase I exhibited saturation kinetics on
      0.05-2.5 mM hemithioacetal concentration range, with kinetic parameters Km 0.53
      +/- 0.07 mM and V (3.18 +/- 0.16) x 10(-2) mM.min(-1). Glyoxalase II also showed
      saturation kinetics in the SD-lactoylglutathione concentration range of 0.15-3 mM
      and Km 0.32 +/- 0.13 mM and V (1.03 +/- 0.10) x 10(-3) mM.min(-1) were obtained.
      The kinetic parameters of both enzymes were also estimated by nonlinear
      regression of progress curves using the raw absorbance data and integrated
      differential rate equations with the program GEPASI. Several optimization methods
      were used to minimize the sum of squares of residuals. The best parameter fit for
      the glyoxalase I reaction was obtained with a single curve analysis, using the
      irreversible Michaelis-Menten model. The kinetic parameters obtained, Km 0.62 +/-
      0.18 mM and V (2.86 +/- 0.01) x 10(-2) mM.min(-1), were in agreement with those
      obtained by initial rate analysis. The results obtained for glyoxalase II, using
      either the irreversible Michaelis-Menten model or a phenomenological reversible
      hyperbolic model, showed a high correlation of residuals with time and/or high
      values of standard deviation associated with Km. The possible causes for the
      discrepancy between data obtained from initial rate analysis and progress curve
      analysis, for glyoxalase II, are discussed.

PMID- 11453986
TI  - Probing the role of oligomerization in the high thermal stability of Pyrococcus
      furiosus ornithine carbamoyltransferase by site-specific mutants.
AB  - The Pyrococcus furiosus ornithine carbamoyltransferase (OTCase) is extremely heat
      stable and maintains 50% of its catalytic activity after 60 min at 100 degrees C.
      The enzyme has an unusual quaternary structure when compared to anabolic OTCases
      from mesophilic organisms. It is built up of four trimers arranged in a
      tetrahedral manner, while other anabolic enzymes are single trimers. Residues
      Trp21, Glu25, Met29 and Trp33 are located in the main interfaces that occur
      between the catalytic trimers within the dodecamer. They participate in either
      hydrophobic clusters or ionic interactions. In order to elucidate the role played
      by the oligomerization in the enzyme stability at very high temperatures, we
      performed mutagenesis studies of these residues. All the variants show similar
      catalytic activities and kinetic properties when compared to the wild-type
      enzyme, allowing the interpretation of the mutations solely on heat stability and
      quaternary structure. The W21A variant has only a slight decrease in its
      stability, and is a dodecamer. The variants E25Q, M29A, W33A, W21A/W33A and
      E25Q/W33A show that altering more drastically the interfaces results in a
      proportional decrease in heat stability, correlated with a gradual dissociation
      of dodecamers into trimers. Finally, the E25Q/M29A/W33A variant shows a very
      large decrease in heat stability and is a trimer. These results suggest that
      extreme thermal stabilization of this OTCase is achieved in part through
      oligomerization.

PMID- 11453987
TI  - Allosteric activation of pyruvate kinase via NAD+ in rat liver cells.
AB  - In isolated rat hepatocytes, it has previously been reported that a rise in the
      ATP content induces a proportional increase in cytosolic NAD+ concentration
      [Devin, A., Guerin, B. & Rigoulet, M. (1997) FEBS Lett. 410, 329-332]. This
      occurs under physiological conditions such as various substrates or different
      energetic states. To investigate the effect of a physiological rise in cytosolic
      [NAD+] per se on glycolysis and gluconeogenesis, an increase in [NAD+] induced by
      exogenous nicotinamide addition was obtained without a change in redox potential,
      ATP/ADP ratio and ATP concentration. Using dihydroxyacetone as substrate, we
      found that an increase in cytosolic [NAD+] decreases gluconeogenesis and enhances
      glycolysis without significant alteration of dihydroxyacetone consumption rate.
      These modifications are the consequence of an allosteric activation of pyruvate
      kinase via cytosolic NAD+ content. Thus, in addition to the well-known
      thermodynamic control of glycolysis by pyridine-nucleotide redox status, our
      study points to a new mechanism of glycolytic flux regulation by NAD+
      concentration at the level of pyruvate kinase activity.

PMID- 11453988
TI  - The conserved Asn49 of maize glutathione S-transferase I modulates substrate
      binding, catalysis and intersubunit communication.
AB  - The functional and structural role of the conserved Asn49 of theta class maize
      glutathione S-transferase was investigated by site-directed mutagenesis. Asn49 is
      located in the type I beta turn formed by residues 49-52, and is involved in
      extensive hydrogen-bonding interactions between alpha helix 2 and the rest of the
      N-terminal domain. The substitution of Asn49 with Ala induces positive
      cooperativity for 1-chloro-2,4-dinitrobenzene (CDNB) binding as reflected by a
      Hill coefficient of 1.9 (S(0.5)CDNB = 0.43 mm). The positive cooperativity is
      also confirmed by following the isothermic binding of 1-hydroxyl-2,4
      dinitrobenzene (HDNB) by UV-difference spectroscopy. In addition, the mutated
      enzyme exhibits: (a) an increase in the Km(GSH) value of about 6.5-fold, and
      decrease in kcat value of about fourfold; (b) viscosity-independent kinetic
      parameters; (c) lower thermostability, and (d) increased susceptibility to
      proteolytic attack by trypsin, when compared to the wild-type enzyme. It is
      concluded that Asn49 affects the rate-limiting step of the catalytic reaction,
      and contributes significantly to the structural and binding characteristics of
      both the glutathione binding site (G-site) and the electrophile substrate binding
      site (H-site) by affecting the structural integrity of a type I beta turn
      (comprising residues 49-52) and probably the flexibility of the highly mobile
      short 310 helical segment of alpha helix 2 (residues 35-46). These structural
      perturbations are probably transmitted, via Phe51 and Phe65, to alpha helix H3"
      of the adjacent subunit which contains key residues that interact with the
      electrophile substrate and contribute to the monomer-monomer contact region. This
      may accounts for the positive cooperativity observed.

PMID- 11453989
TI  - Rapid and cooperative binding of factor XII to human umbilical vein endothelial
      cells.
AB  - When activated, factor XII (FXII) has been shown to play a role in a series of
      proteolytic cascades including systems as the fibrinolytic, the coagulation, the
      kallikrein-kinin and the complement. How FXII is activated in vivo remains poorly
      understood as the concentration and density of surface bound negative charges
      known to trigger the activation in vitro is far from sufficient in vivo. Specific
      binding of FXII to cellular receptors in the blood stream may, however, solve
      this problem which may be a question of inter molecular vicinity enhanced by
      binding to any surface. Here we report that the Zn(2+)-dependent binding of FXII
      to endothelial cells is rapid, saturable, specific and cooperative. Each
      endothelial cell from the human umbilical veins was found to bind (417 +/- 202) x
      10(3) molecules of FXII with a Kd of (65 +/- 23) nM and a Hill coefficient of
      2.1. The binding was inhibited by alpha-FXIIa but not by beta-FXIIa. The Kd for
      binding alpha-FXIIa was (50 +/- 27) nM. The rate of association was found to be
      1.9 x 10(5) M(-1). min(-1). A confirmed inhibition by HK increased the Kd without
      affecting the maximal number of binding sites and the Hill coefficient. The
      concentration of HK in serum did not prevent binding of FXII/FXIIa to cells
      incubated with serum supplemented with Zn2+. The optimal concentration of Zn(2+)
      was 15 microM for binding factor XII/FXIIa whether purified or in serum.

PMID- 11453990
TI  - Complex of Burkholderia cepacia lipase with transition state analogue of 1
      phenoxy-2-acetoxybutane: biocatalytic, structural and modelling study.
AB  - In a series of four racemic phenoxyalkyl-alkyl carbinols, 1-phenoxy-2
      hydroxybutane (1) is enantioselectively acetylated by Burkholderia cepacia
      (formerly Pseudomonas cepacia) lipase with an E value > or = 200, whereas for the
      other three racemates E was found to be < or = 4. To explain the high preference
      of B. cepacia lipase for (R)-(+)-1, a precursor of its transition state analogue
      with a tetrahedral P-atom, (R(P),S(P))-O-(2R)-(1-phenoxybut-2-yl)methylphosphonic
      acid chloride was prepared and crystallized in complex with B. cepacia lipase.
      The X-ray structure of the complex was determined, allowing to compare the
      conformation of the inhibitor with results of molecular modelling.

PMID- 11453991
TI  - Deduced amino-acid sequence of a calcium-free alpha-amylase from a strain of
      Bacillus: implications from molecular modeling of high oxidation stability and
      chelator resistance of the enzyme.
AB  - Alkaline alpha-amylase (AmyK38) from the alkaliphilic Bacillus sp. strain KSM-K38
      is a unique enzyme in that it is highly chelator-resistant and oxidatively stable
      [Hagihara, H., Igarashi, K., Hayashi, Y., Endo, K., Ikawa-Kitayama, K., Ozaki,
      K., Kawai, S. & Ito, S. (2001) Appl. Environ. Microbiol. 67, 1744-1750]. This
      enzyme was found to contain no Ca and require Na (or monovalent cations) for
      manifestation of activity. The nucleotide sequence of the gene for the novel
      enzyme was determined, and it harbored an ORF of 1503 bp encoding the enzyme of
      501 amino acids, including a 21-amino-acid signal peptide. The deduced amino-acid
      sequence of the mature enzyme (55 097 Da) showed moderate homology to those of
      alpha-amylases from Bacillus licheniformis, Bacillus stearothermophilus and
      Bacillus amyloliquefaciens, with approximately 63% identity. A methionine
      residue, which is conserved and susceptible to chemical oxidation, was replaced
      with leucine in AmyK38. Moreover, many conserved residues that are crucial
      ligands for Ca were replaced with other amino acids, thereby leading to loss of
      the Ca coordination geometries. By building a molecular model, we showed the
      calcium-independent, oxidatively stable active-site topology and structural
      integrity of AmyK38.

PMID- 11453992
TI  - The fatty acid composition of chylomicron remnants influences their binding and
      internalization by isolated hepatocytes.
AB  - The binding and internalization of (125)I-labelled chylomicron remnants derived
      from palm, olive, corn, or fish oil (rich in saturated, monounsaturated, n-6, or
      n-3 polyunsaturated fatty acids, respectively) by hepatocytes from rats fed a low
      fat diet or a diet supplemented with the corresponding fat for 21 days was
      investigated. In hepatocytes from rats fed the low-fat diet, the association of
      radioactivity with the cells at 4 degrees C (a measure of initial binding only)
      was similar with all types of remnants tested, but was more rapid at 37 degrees C
      (a measure of binding plus internalization) when fish oil, as compared to olive,
      corn or palm oil remnants, was used, and similar differences in the
      internalization of the particles were observed. In contrast, when hepatocytes
      from rats fed the fat-supplemented diets were used, the rate of association at 37
      degrees C of remnants with cells from rats fed palm, corn or fish oil was
      similar, and higher than that found with cells from animals fed olive oil, and in
      this case these differences were mainly due to changes in the binding of the
      particles to the cells at 4 degrees C. Both excess low-density lipoprotein (LDL),
      which inhibits remnant uptake by the LDL receptor, and lactoferrin, which blocks
      the LDL receptor-related protein (LRP), were found to decrease the association of
      the remnants with cells from rats fed the low-fat and high-fat diets. However, in
      hepatocytes from animals given the low-fat diet, most of the differences between
      the various types of particle were retained in the presence of lactoferrin, but
      abolished in the presence of LDL. In contrast, in cells from rats fed the high
      fat diets, the differences were reduced by both lactoferrin and LDL. These
      findings demonstrate that the hepatic uptake of chylomicron remnants is
      influenced both by the fatty acid composition of the particles, and by longer
      term adaptive changes in liver tissue, and suggest that the former effects are
      mediated mainly by the LDL receptor, while the latter may involve both the LDL
      receptor and the LRP.

PMID- 11453993
TI  - The contribution of metal ions to the conformational stability of ribonuclease
      T1: crystal versus solution.
AB  - In the crystalline state, ribonuclease T1 binds calcium ions at different lattice
      dependent positions. In solution, its conformational stability is also remarkably
      increased in the presence of divalent metal ions. Combining urea unfolding
      studies and X-ray crystallography, we compared the presence of several metal ions
      at specific sites in the protein to their contribution to the overall stabilizing
      effect in solution. We constructed thermodynamic cycles involving particular
      metal ions and specific carboxylate functions. The resulting coupling energies
      indicate that some (but not all) metal ions found at lattice contacts in crystal
      structures may indeed significantly contribute to stability enhancement in the
      presence of metal ions in solution.

PMID- 11453994
TI  - Dichloromethane mediated in vivo selection and functional characterization of rat
      glutathione S-transferase theta 1-1 variants.
AB  - Methylobacterium dichloromethanicum DM4 is able to grow with dichloromethane as
      the sole carbon and energy source by using a dichloromethane
      dehalogenase/glutathione S-transferase (GST) for the conversion of
      dichloromethane to formaldehyde. Mammalian homologs of this bacterial enzyme are
      also known to catalyze this reaction. However, the dehalogenation of
      dichloromethane by GST T1-1 from rat was highly mutagenic and toxic to
      methylotrophic bacteria. Plasmid-driven expression of rat GST T1-1 in strain DM4
      2cr, a mutant of strain DM4 lacking dichloromethane dehalogenase, reduced cell
      viability 10(5)-fold in the presence of dichloromethane. This effect was
      exploited to select dichloromethane-resistant transconjugants of strain DM4-2cr
      carrying a plasmid-encoded rGSTT1 gene. Transconjugants that still expressed the
      GST T1 protein after dichloromethane treatment included rGSTT1 mutants encoding
      protein variants with sequence changes from the wild-type ranging from single
      residue exchanges to large insertions and deletions. A structural model of rat
      GST T1-1 suggested that sequence variation was clustered around the glutathione
      activation site and at the protein C-terminus believed to cap the active site.
      The enzymatic activity of purified His-tagged GST T1-1 variants expressed in
      Escherichia coli was markedly reduced with both dichloromethane and the
      alternative substrate 1,2-epoxy-3-(4'-nitrophenoxy)propane. These results provide
      the first experimental evidence for the involvement of Gln102 and Arg107 in
      catalysis, and illustrate the potential of in vivo approaches to identify
      catalytic residues in GSTs whose activity leads to toxic effects.

PMID- 11453995
TI  - Purification and characterization of the heterologously expressed
      trehalose/maltose ABC transporter complex of the hyperthermophilic archaeon
      Thermococcus litoralis.
AB  - We report the purification of the maltose/trehalose transporter complex MalFGK of
      the hyperthermophilic archaeon Thermococcus litoralis. The complex was expressed
      in Escherichia coli, solubilized in dodecyl maltoside and purified with the aid
      of a histidine tag on one of the membrane proteins. One hundred grams of cells
      yielded 3 mg of pure complex. The final product showed ATPase activity at 70
      degrees C and was soluble at low detergent concentration. ATPase activity was not
      due to dissociation of the MalK subunit from the integral membrane proteins MalF
      and MalG but could not be further stimulated by trehalose/maltose binding protein
      (TMBP), be it the native protein as isolated from T. litoralis or the soluble
      engineered protein. The purified native TMBP was identified as a glycoprotein.

PMID- 11453996
TI  - Characterization and reconstitution of functional hemagglutinin of the
      Clostridium botulinum type C progenitor toxin.
AB  - The purified progenitor toxin of Clostridium botulinum type C strain 6814 (C
      6814) forms a large complex composed of 150-kDa neurotoxin (NT), 130-kDa nontoxic
      nonhemagglutinin (NTNHA), and hemagglutinin (HA) components. The HA component
      consisted of a mixture of several subcomponents with molecular masses of 70, 55,
      33, 26-21 and 17 kDa. We isolated the HA subcomponents from the progenitor toxin
      by chromatography in the presence of denaturants. The isolated HA subcomponents,
      designated as i-HA-33, i-HA-55, i-HA-70 and i-HA-33/17, were nearly homogeneous
      on SDS/PAGE, but the HA-17 and HA-26-21 components were not purified. Some HA
      subcomponents, designated as f-HA-33 and f-HA-33/17 complex, existed free of the
      progenitor toxin in the culture medium and they were separately purified. Every
      HA subcomponent so far isolated shows binding activity to erythrocytes. The
      hemagglutination activities of each HA subcomponent had a titer of 25 for the f
      HA-33/17 complex, and below 23 for the other f- and i-HA subcomponents, while the
      parent progenitor L toxin was 28. The reconstitution of various combinations of f
      and i-HA subcomponents was attempted via mixing and tested for hemagglutination
      activity. When the i-HA-33/17 complex and i-HA-55 were mixed, the
      hemagglutination activity was recovered to a titer of 29, which was slightly
      higher than that of the parent toxin. These data imply that a combination of at
      least HA-33, -17 and -55 subcomponents is required for full hemagglutination
      activity of the botulinum progenitor toxin, but each single HA subcomponent shows
      weak or no aggregation of erythrocytes.

PMID- 11453997
TI  - Blood digestion in the malaria mosquito Anopheles gambiae: molecular cloning and
      biochemical characterization of two inducible chymotrypsins.
AB  - The elucidation of digestive processes in the Anopheles gambiae gut leading to
      the utilization of the blood meal will result in a deeper understanding of the
      physiology of blood digestion and its impact on parasite-vector interactions.
      Accordingly, the identification of digestive serine proteases in A. gambiae has
      implications for the development of alternative strategies for the control of
      mosquito-borne diseases. We report here on the cDNA and genomic cloning and on
      the expression analysis of two closely related chymotrypsin genes, Anchym1 and
      Anchym2. Genomic cloning revealed that Anchym1 and Anchym2, which map on
      chromosomal division 25D, are clustered in tandem within 6 kb, both genes being
      interrupted by two short introns. After blood feeding, transcription of Anchym1
      and Anchym2 is induced in the midgut epithelium, followed by secretion of the
      translated products into the midgut lumen where the Anchym1 and Anchym2 zymogens
      are activated by partial tryptic digestion. The amino-acid residues forming the
      substrate pocket of Anchym1 and Anchym2 suggested chymotryptic cleavage
      specificity. This was confirmed by mass spectrometry analysis and Edman
      degradation sequencing of proteolytic products generated by the recombinant,
      trypsin-activated Anchym1.

PMID- 11453998
TI  - The N-terminal portion of the preToc75 transit peptide interacts with membrane
      lipids and inhibits binding and import of precursor proteins into isolated
      chloroplasts.
AB  - Toc75 is an outer envelope membrane protein of chloroplasts. It is unusual among
      the outer membrane proteins in that its precursor form has a bipartite transit
      peptide. The N-terminal portion of the Toc75 transit peptide is sufficient to
      target the protein to the stromal space of chloroplasts. We prepared a 45 amino
      acid peptide containing the stromal targeting domain of the Toc75 transit peptide
      in Escherichia coli, using the intein-mediated system, and purified it by reverse
      phase HPLC. Its identity was confirmed by N-terminal amino-acid sequencing and
      matrix assisted laser desorption ionization mass spectrometry. In monolayer
      experiments, the peptide inserted into the chloroplastic membrane lipids
      sulfoquinovosyl diacylglycerol and phosphatidylglycerol and into a
      nonchloroplastic lipid phosphatidylethanolamine. However, it did not insert into
      other chloroplastic lipids, such as mono- and digalactosyl diacylglycerol, and
      phosphatidylcholine. Furthermore, the peptide significantly inhibited binding of
      radiolabeled precursors of Toc75 and the small subunit of ribulose-1,5
      bisphosphate carboxylase/oxygenase to intact chloroplasts as effectively as did a
      bacterially produced precursor of the small subunit of 1,5-bisphosphate
      carboxylase/oxygenase. The peptide also inhibited import of radiolabeled
      precursors into isolated chloroplasts, however, to a lesser extent than did
      nonlabeled precursor of the small subunit of 1,5-bisphosphate
      carboxylase/oxygenase.

PMID- 11453999
TI  - Structure and characterization of the glycan moiety of L-amino-acid oxidase from
      the Malayan pit viper Calloselasma rhodostoma.
AB  - Ophidian L-amino-acid oxidase (L-amino-acid oxygen:oxidoreductase, deaminating,
      EC 1.4.3.2) is found in the venom of many poisonous snakes (crotalids, elapids
      and viperids). This FAD-dependent glycoprotein has been studied from several
      snake species (e.g. Crotalus adamanteus, Crotalus atrox and Calloselasma
      rhodostoma) in detail with regard to the biochemical and enzymatic properties.
      The nature of glycosylation, however, as well as the chemical structure(s) of the
      attached oligosaccharide(s) are unknown. In view of the putative involvement of
      the glycan moiety in the biological effects of ophidian L-amino-acid oxidase,
      notably the apoptotic activity of the enzyme, structural knowledge is needed to
      evaluate its exact function. In this study we report on the glycosylation of L
      amino-acid oxidase from the venom of the Malayan pit viper (Calloselasma
      rhodostoma). Its glycosylation is remarkably homogeneous with the major
      oligosaccharide accounting for approximately 90% of the total sugar content.
      Based on detailed analysis of the isolated oligosaccharide by 2D NMR
      spectroscopies and MALDI-TOF mass spectrometry the glycan is identified as a bis
      sialylated, biantennary, core-fucosylated dodecasaccharide. The biological
      significance of this finding is discussed in light of the biological activities
      of the enzyme.

PMID- 11454000
TI  - CYP11A1 stimulates the hydroxylase activity of CYP11B1 in mitochondria of
      recombinant yeast in vivo and in vitro.
AB  - In mammals, hydrocortisone synthesis from cholesterol is catalyzed by a set of
      five specialized enzymes, four of them belonging to the superfamily of cytochrome
      P-450 monooxygenases. A recombinant yeast expression system was recently
      developed for the CYP11B1 (P45011beta) enzyme, which performs the 11beta
      hydroxylation of steroids such as 11-deoxycortisol into hydrocortisone, one of
      the three mitochondrial cytochrome P-450 proteins involved in steroidogenesis in
      mammals. This heterologous system was used to test the potential interaction
      between CYP11B1 and CYP11A1 (P450scc), the mitochondrial cytochrome P-450 enzyme
      responsible for the side chain cleaving of cholesterol. Recombinant CYP11B1 and
      CYP11A1 were targeted to Saccharomyces cerevisiae mitochondria using the yeast
      cytochrome oxidase subunit 6 mitochondrial presequence fused to the mature form
      of the two proteins. In yeast, the presence of CYP11A1 appears to improve 11beta
      hydroxylase activity of CYP11B1 in vivo and in vitro. Fractionation experiments
      indicate the presence of the two proteins in the same membrane fractions, i.e.
      inner membrane and contact sites of mitochondria. Thus, yeast mitochondria
      provide interesting insights to study some molecular and cellular aspects of
      mammalian steroid synthesis. In particular, recombinant yeast should permit a
      better understanding of the mechanism permitting the synthesis of steroids (sex
      steroids, mineralocorticoids and glucocorticoids) with a minimal set of enzymes
      at physiological level, thus avoiding disease states.

PMID- 11454001
TI  - A family of novel, acidic N-glycans in Bowes melanoma tissue plasminogen
      activator have L2/HNK-1-bearing antennae, many with sulfation of the fucosylated
      chitobiose core.
AB  - A family of about 20 novel acidic bi- and tri-antennary N-glycans, amounting to
      almost half those expressed on Bowes melanoma tissue-plasminogen activator (t-PA)
      were found to possess Galbeta1-->4GlcNAcbeta1-->, sulfated and sialylated
      GalNAcbeta1-->4GlcNAcbeta1--> or sulfated GlcAbeta1--> 3Galbeta1-->4GlcNAcbeta1-
      > antennae, of which those containing sulfated GlcA, depicting the L2/HNK-1
      carbohydrate epitope, were preferentially located on the 6 arm. A proportion of
      the glycans were highly charged, because of multiple and variously distributed
      sulfation, some of which was located on the fucosylated chitobiose core. Multiple
      expression of the L2/HNK-1 epitope on a single glycan was observed. The most
      abundant compound was a biantennary glycan carrying sulfated GlcA on the 6
      branched antenna and an alpha2-->6 sialylated GalNAc on the other. The N
      glycosylation sequon containing Asn448, which is known to express all of the
      sulfate-carrying N-glycans contains, unusually, an arginine residue. An
      electrostatic interaction between this cationic amino acid and the core-sulfate
      group of the N-glycan is proposed to reduce mobility of the carbohydrate in the
      region of the t-PA active site. Because of the 'brain-type' nature of the N
      glycans described in this neuro-ectodermal cell line, the possibility of neural t
      PA interacting with the L2/HNK-1-recognizing molecule, laminin, of the central
      nervous system extracellular matrix is discussed.

PMID- 11454002
TI  - A novel chitinase having a unique mode of action from Aspergillus fumigatus YJ
      407.
AB  - Chitinases are produced throughout the growth process of fungi and are thought to
      play important roles in morphogenesis. Aspergillus fumigatus, is an important
      pathogen of immunocompromised individuals in which it causes pneumonia and
      invasive disseminated disease with high mortality; it is also known to produce
      chitinase. We have induced an exceptionally stable extracellular chitinase in A.
      fumigatus YJ-407, which could be isolated readily in a homogeneous form by using
      ammonium sulfate precipitation followed by DEAE-cellulose chromatography and
      preparative PAGE. The molecular mass of this chitinase was estimated to be 46 000
      by SDS/PAGE, and its isoelectric point was pH 5.6. The enzyme was most active at
      pH 5.0 and 60 degrees C, and was inhibited strongly by Hg2+, Pb2+, Ag+, Fe2+,
      Mn2+ and Zn2+. The enzyme was stable over a broad pH range 4-8 and below 45
      degrees C. Tryptophan and carboxyl groups were found to be essential for the
      enzyme activity. The Michaelis constants for swollen chitin and chitosan were
      1.12 mg.mL-1 and 1.84 mg.mL-1, respectively. The enzyme showed maximum activity
      towards glycol chitin and partially deacetylated chitosan, and lower activity
      towards colloidal chitin. Analysis of the hydrolysis product showed that the
      enzyme has both endo- and exo-hydrolytic activities. In addition, a transglycosyl
      activity was also observed.

PMID- 11454003
TI  - Molecular cloning and heterologous expression of novel glucosyltransferases from
      tobacco cultured cells that have broad substrate specificity and are induced by
      salicylic acid and auxin.
AB  - Scopoletin is one of the phytoalexins in tobacco. Cells of the T-13 cell line
      (Nicotiana tabacum L. Bright Yellow) accumulate a large amount of scopoletin,
      also known as 7-hydroxy-6-methoxycoumarin, as a glucoconjugate, scopolin, in
      vacuoles. We report here the molecular cloning of glucosyltransferases that can
      catalyze the glucosylation of many kinds of secondary metabolites including
      scopoletin. Two cDNAs encoding glucosyltransferase (NtGT1a and NtGT1b) were
      isolated from a cDNA library derived from the tobacco T-13 cell line by screening
      with heterologous cDNAs as a probe. The deduced amino-acid sequences of NtGT1a
      and NtGT1b exhibited 92% identity with each other, approximately 20-50%
      identities with other reported glucosyltransferases. Heterologous expression of
      these genes in Escherichia coli showed that the recombinant enzymes had
      glucosylation activity against both flavonoids and coumarins. They also strongly
      reacted with 2-naphthol as a substrate. These recombinant enzymes can utilize UDP
      glucose as the sugar donor, but they can also utilize UDP-xylose as a weak donor.
      RNA blot analysis showed that these genes are induced by salicylic acid and
      auxin, but the time course of the expression was different. This result is
      similar to the changes in scopoletin glucosylation activity in these tobacco
      cells after addition of these plant growth regulators. These results might
      suggest that one of the roles of the products of these genes is scopoletin
      glucosylation, in response to salicylic acid and/or auxin, together with the
      other glucosyltransferases in tobacco cells.

PMID- 11454004
TI  - Hormonal regulation of multiple promoters of the rat mitochondrial glycerol-3
      phosphate dehydrogenase gene: identification of a complex hormone-response
      element in the ubiquitous promoter B.
AB  - Rat mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) is regulated by
      multiple promoters in a tissue-specific manner. Here, we demonstrate that thyroid
      hormone (3,5,3'-tri-iodo-L-thyronine) and steroid hormone but not the peroxisome
      proliferator clofibrate and retinoic acid stimulate the activation of the
      ubiquitous promoter B in a receptor-dependent manner, whereas the more tissue
      restricted promoters A and C are not inducible by these hormones. Thyroid hormone
      action is mediated by a direct repeat +4 (DR+4) hormone-response element as
      identified by deletion and mutation analyses of promoter B in transient
      transfection analyses. The DR+4 element was able to bind to an in vitro
      translated thyroid hormone receptor in band-shift and supershift experiments. The
      hormone-response element comaps with a recognition site for the transcription
      factor Sp1, suggesting complex regulation of this sequence element. Mutation of
      this Sp1-recognition site reduces the basal promoter B activity dramatically in
      HepG2 and HEK293 cells in transient transfection and abolishes the binding of Sp1
      in band-shift experiments. As demonstrated by Western-blot experiments,
      administration of tri-iodothyronine to euthyroid rats increases hepatic mGPDH
      protein concentrations in vivo. As it has recently been reported that human mGPDH
      promoter B is not regulated by tri-iodothyronine, this is the first example of a
      differentially tri-iodothyronine-regulated orthologous gene promoter in man and
      rat.

PMID- 11454005
TI  - The hemoglobin system of the brown moray Gymnothorax unicolor: structure/function
      relationships.
AB  - The Gymnothorax unicolor hemoglobin system is characterized by two components,
      called cathodic and anodic on the basis of their isoelectric point, which were
      separated by ion-exchange chromatography. The oxygen-binding properties of the
      purified components were studied in the absence and presence of chloride and/or
      GTP or ATP in the pH range 6.5-8.0. Stripped cathodic hemoglobin showed a small
      reverse Bohr effect, high oxygen affinity, and low co-operativity; the addition
      of chloride only caused a small decrease in oxygen affinity. In the presence of
      GTP or ATP, the oxygen affinity was dramatically reduced, the co-operativity
      increased, and the reverse Bohr effect abolished. Stripped anodic hemoglobin is
      characterized by both low oxygen affinity and co-operativity, and displayed a
      normal Bohr effect; the addition of chloride increased co-operativity, whereas
      ATP and GTP significantly modulated oxygen affinity at acidic pH values,
      enhancing the Bohr effect and giving rise to the Root effect. The complete amino
      acid sequences of the alpha and beta chains of both hemoglobins were established;
      the molecular basis of the functional properties of the hemoglobins is discussed
      in the light of the primary structure and compared with those of other fish
      hemoglobins.

PMID- 11454006
TI  - T peak-Tend interval as an index of transmural dispersion of repolarization.

PMID- 11454007
TI  - An unsolved mystery of promoter variation in CETP gene and atherosclerosis.

PMID- 11454008
TI  - Triglycerides and endothelial function in type 2 diabetes.

PMID- 11454009
TI  - Left ventricular hypertrophy increases transepicardial dispersion of
      repolarisation in hypertensive patients: a differential effect on QTpeak and
      QTend dispersion.
AB  - BACKGROUND: Ventricular arrhythmias in left ventricular hypertrophy (LVH) are
      related to regional electrical heterogeneity. The significance of noninvasive
      electrocardiographic indices of electrical heterogeneity in LVH has not been
      established. The aim of the study was to investigate changes in the Tpeak-Tend
      interval (an index of transmural dispersion of repolarisation) in addition to
      other traditional electrocardiographic indices of electrical dispersion in
      patients with hypertensive LVH. METHODS: Consecutive patients were screened for
      the presence of hypertensive echocardiographic LVH and compared with a control
      group. LVH was identified as left ventricular mass > 134 g m-2 in men and > 110 g
      m-2 in women. Twelve-lead ECGs were analysed in respect of various indices of
      electrical dispersion. RESULTS: Left ventricular mass was greater in the LVH than
      in the control group (174 +/- 39 vs. 101 +/- 18 g m-2, P < 0.0001). The Tpeak
      Tend interval was not affected by LVH. The main effect of LVH was an increase in
      QTpeak dispersion (40 +/- 13 vs. 53 +/- 21 ms, P < 0.05), which resulted from an
      increase in the maximum QTpeak interval (337 +/- 24 vs. 358 +/- 30 ms, P < 0.04),
      without any change in the minimum QTpeak interval. There was a significant
      correlation between the left ventricular mass index and QTpeak dispersion (r =
      0.40; P < 0.01). In contrast, LVH did not exert any effect on QTend dispersion
      (65 +/- 21 vs. 65 +/- 16 ms, ns), because LVH increased both the maximum QTend
      interval (430 +/- 30 vs. 449 +/- 28 ms, P < 0.05) and the minimum QTend interval
      (365 +/- 29 vs. 384 +/- 27 ms, P < 0.04). CONCLUSIONS: Hypertensive LVH exerts a
      differential effect on QTpeak and QTend interval dispersion. The most likely
      explanation is that these changes reflect a nonuniform prolongation of action
      potential duration across the epicardium, leading to an increase in
      transepicardial dispersion of repolarisation.

PMID- 11454010
TI  - Lack of association between apolipoprotein E genoype and ischaemic stroke in a
      Scottish population.
AB  - BACKGROUND: Apolipoprotein E epsilon4 allele has been associated with increased
      risk of coronary heart disease, and is also a major genetic susceptibility locus
      for Alzheimer's disease. Some studies have shown an association between apoE
      genotype and ischaemic stroke or outcome following stroke, while other studies
      have failed to do so. Materials and methods Using PCR and the Taqman fluorescence
      system to detect polymorphisms we examined apoE genotype in 266 ischaemic stroke
      cases and in a control population. RESULTS: We found no association between apoeE
      epsilon 4 allele distribution and ischaemic stroke, or with outcome following
      stroke as measured using the Rankin score. Conclusion This study disagrees with a
      recent meta-analysis, and suggests that further studies are required to clarify
      the exact relationship between apoE genotype and ischaemic stroke.

PMID- 11454011
TI  - Hepatic lipase gene variation is related to coronary reactivity in healthy young
      men.
AB  - BACKGROUND: Impaired coronary flow reserve (CFR) can be used to indicate vascular
      dysfunction before the appearance of angiographic lesions. The hepatic lipase
      (HL) gene has a functional promoter polymorphism at position C-480T, which
      affects transcription and leads to high activity (C/C) and low activity (C/T,
      T/T) genotypes. These genotypes modulate HL activity, but their role in coronary
      artery disease is controversial and the effect on coronary function has not been
      studied. We investigated whether HL genotypes are associated with coronary artery
      function in healthy young men. MATERIALS AND METHODS: We studied 49 healthy,
      mildly hypercholesterolemic men (aged 35 +/- 4 years). Myocardial blood flow was
      measured at rest and during adenosine induced hyperaemia with positron emission
      tomography using [15O] H2O. HL genotype was determined by PCR and Nla III enzyme
      digestion. RESULTS: Resting myocardial blood flow was not statistically different
      in subjects with high and low activity HL genotypes. However, CFR (the ratio of
      adenosine flow to resting flow) was 24% higher (4.62 +/- 1.52 vs. 3.73 +/- 1.08
      mL g-1 min-1, P = 0.024) in men with the high activity genotype (n = 26) than in
      those with low activity (n = 23). In multivariate analysis, the HL genotype
      remained a significant predictor of CFR (P = 0.038) after adjusting for age, body
      mass index, serum lipids and smoking. CONCLUSIONS: The findings of our
      preliminary study suggest that the C-480T polymorphism of the HL gene may modify
      coronary reactivity and reflect differences in the early pathogenesis of coronary
      dysfunction in these healthy young men. If the association between HL
      polymorphism and impaired CFR is also present in subjects with other
      dyslipoproteinemias, the HL polymorphism could be a new risk factor for
      cardiovascular disease.

PMID- 11454012
TI  - Serum homocysteine does not associate with uncomplicated coronary heart disease.
AB  - BACKGROUND: Elevated serum homocysteine concentrations have been related to
      coronary heart disease. However, the association has not indisputably been
      proven, and the mechanisms by which homocysteine may be atherogenic have only
      partially been elucidated. The objective of the present study was to investigate
      whether serum homocysteine is associated with angina pectoris and myocardial
      infarction. METHODS: We compared serum homocysteine concentrations in subjects
      with clinical evidence of angina pectoris or history of myocardial infarction to
      age-matched controls. The study included 248 males, who participated in a large
      cross-sectional risk factor survey carried out in five geographic areas in
      Finland. RESULTS: Serum homocysteine concentration was significantly higher in
      subjects with a history of myocardial infarction compared to controls (15.3
      micromol L-1 and 13.9 micromol L-1 respectively, P = 0.037). In a logistic
      regression model including several cardiovascular risk factors, serum
      homocysteine was significantly associated with myocardial infarction (95% CI
      1.0157-1.2990, P = 0.027). Serum homocysteine concentrations did not differ
      between subjects with angina pectoris and age-matched controls (13.9 micromol L-1
      and 14.2 micromol L-1 respectively). CONCLUSIONS: Our results suggest that
      elevated serum homocysteine is associated with myocardial infarction but not with
      uncomplicated coronary heart disease.

PMID- 11454013
TI  - Impaired fibrinolysis determines the outcome of percutaneus transluminal coronary
      angioplasty (PTCA).
AB  - BACKGROUND: Coronary artery stenosis lesions dilated by percutaneus transluminal
      coronary angioplasty (PTCA) show a disappointingly frequent recurrence of
      stenosis. We have investigated the possible role of fibrinolysis and various
      platelet-release factors - specifically in the locality of the affected vessel -
      by following 19 patients for 6 months after PTCA. METHODS: PTCA was performed on
      19 patients with a significant primary coronary stenosis, proven by quantitative
      CAAS analysis. Blood for measurement of local fibrinolysis and platelet activity
      was drawn from the aortic root and the coronary sinus, at three times: just
      before PTCA, 10 min after it, and 6 months later. RESULTS: The incidence of
      restenosis at the 6 months follow-up was 37%. PTCA almost doubled the platelet
      derived growth factor level (PDGF) in coronary sinus blood in all patients. The
      seven restenosis patients had a substantially higher tissue plasminogen activator
      inhibitor antigen (PAI-1ag) level in the aortic root before PTCA than the 12 who
      remained stenosis-free (mean 62.4 +/- 31.6 ng mL -1 compared with 33.1 + 25.3; P
      < 0.04) and a lower tissue plasminogen activator activity (t-PAac) level (mean
      0.32 +/- 0.19 IU mL-1 compared with 0.68 +/- 0.34; P < 0.03). This was
      corroborated by the levels of tissue plasminogen activator inhibitor activity
      (PAI-1ac). At reassessment after 6 months, the restenosis patients had developed,
      in coronary sinus blood, a large rise of PAI-1ac (7.7 +/- 4.8 IU mL-1 rising to
      15.7 +/- 13.9, P < 0.04) and a large rise of of PAI-1ag (48.8 +/- 31.3 ng mL-1
      vs. 72.4 +/- 47.2; P < 0.03). But no such increase occurred in the patients who
      remained stenosis-free. Conclusion Our results indicate that the minor balloon
      injury, which is inseparable from PCTA, stimulates the local release of PDGF. We
      suggest that, in those patients whose fibrinolytic activity is inherently low,
      this rise of PDGF could be a major causative factor in restenosis. We also
      discuss the possibility that the preoperative level of PAI-1ac could provide a
      limited but useful prediction of the outcome of PTCA.

PMID- 11454014
TI  - Variation at the cholesteryl ester transfer protein gene in relation to plasma
      high density lipoproteins cholesterol levels and carotid intima-media thickness.
AB  - BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a major role in
      lipoprotein metabolism. We have screened the CETP gene for mutations and
      polymorphisms regulating high density lipoproteins cholesterol (HDL-C) levels and
      the development of atherosclerosis, and found some polymorphisms (I405V and
      R451Q) to have minor effects. DESIGN: The purpose of this study was to
      investigate the combined effect of the several polymorphisms of the CETP gene so
      far found on HDL-C levels and carotid intima-media thickness (IMT), and, in
      addition, to study whether the recently found functional polymorphism in the
      promoter region of the CETP gene (C to A, - 629 relative to the first transcribed
      nucleotide) explains the previous associations due to linkage disequilibrium. The
      genotypes were determined in a population sample of 481 men and women. RESULTS:
      There were no significant differences in plasma CETP activity or carotid IMT
      between the genotypes of the promoter polymorphism. The women with the CC
      genotype of the promoter polymorphism had the lowest HDL-C levels (P < 0.001),
      but no such difference was seen in men. Detected polymorphisms of the CETP gene
      explained about 8% of the variation in HDL-C in women and about 7 and 10% of the
      variation in carotid IMT in women and men, respectively. The associations of the
      promoter, I405V and R451Q-A373P polymorphisms with HDL-C and carotid IMT seemed
      to be independent of each other. The associations with IMT were independent of
      total HDL-C levels, suggesting that HDL subfractions may have more effect on IMT.
      CONCLUSION: The CETP gene locus was found to be polymorphic and its polymorphisms
      explained a reasonable proportion of the variation in the degree of carotid
      atherosclerosis.

PMID- 11454015
TI  - Gemfibrozil improves insulin sensitivity and flow-mediated vasodilatation in type
      2 diabetic patients.
AB  - BACKGROUND: Endothelial dysfunction is an early feature of atherosclerosis. The
      relationship between insulin action and hypertriglyceridaemia on endothelial
      function is still debated. MATERIALS AND METHODS: This study was designed to
      determine the effect of a 3 month treatment with Gemfibrozil (GF) on flow
      mediated vasodilatation and insulin sensitivity. Ten type 2 diabetic patients
      were randomised in crossover, double blind fashion, either to GF, 600 mg b.i.d.
      or placebo, for 12 weeks. Lipid profile, low-density lipoprotein (LDL)
      distribution and flotation properties, insulin action and flow-mediated
      vasodilatation (FMD) by brachial artery ultrasound, were assessed. RESULTS: GF
      decreased serum triglyceride (TG) concentration with an absolute difference of
      1.79 +/- 1.28 mmol L-1 (P < 0.0016) between active treatment and placebo, and
      significantly increased serum high-density lipoprotein (HDL) cholesterol (P =
      0.0233). No differences were observed in total, intermediate-density lipoproteins
      (IDL), LDL cholesterol concentration and LDL peak buoyancy between treatments. GF
      also improved SI, an index of insulin action (P = 0.005). The FMD was 7 +/- 3% in
      the baseline condition, 7 +/- 2% during placebo and 14 +/- 3% after GF (P <
      0.006). CONCLUSIONS: GF treatment improves both insulin action and flow-mediated
      vasodilatation in type 2 diabetic patients. The reduction of TG concentration
      allows the simultaneous correction of two important components of the metabolic
      syndrome.

PMID- 11454016
TI  - Human parathyroid cell proliferation in response to calcium, NPS R-467,
      calcitriol and phosphate.
AB  - It remains uncertain how calcium, phosphate and calcitriol regulate parathyroid
      cell growth. The present study was aimed at examining possible direct effects of
      these modulators and of the calcimimetic NPS R-467 on parathyroid cell growth in
      vitro. Cell proliferation was determined by [3H]thymidine incorporation and cell
      cycle antigen Ki 67 expression in a parathyroid cell culture model derived from
      uraemic patients. The effect of NPS R-467 on parathyroid hormone (PTH) secretion
      and intracellular [Ca2+]i response was also examined. Increasing the [Ca2+] in
      the medium from 0.5 to 1.7 mM increased DNA synthesis (P < 0.005) and the number
      of Ki 67-positive cells (P < 0.005). However, NPS R-467 (0.01-1 microM) inhibited
      3[H]thymidine incorporation by 35% in the presence of 0.5 mM [Ca2+]e. Exposure of
      cells to Ca2+ or NPS R-467 led to a rapid increase of intracellular Ca2+,
      although the pattern of increase differed. Addition of calcitriol (10-10-10-7 M)
      to the culture medium suppressed [3H]thymidine incorporation dose-dependently.
      Finally, high levels of phosphate (3.5 mM) in the medium led to a significant (P
      < 0.05) increase in [3H]thymidine incorporation. The observed stimulatory effect
      of Ca2+ in the medium in vitro appears to be at variance with the inhibitory
      effect of calcimimetic NPS R-467 in vitro. In an attempt to solve these apparent
      discrepancies, and based on the notion of a reduced calcium-sensing receptor
      (CaR) expression in parathyroid tissues of uraemic patients, we hypothesize that
      Ca2+ may regulate parathyroid cell proliferation via two different pathways, with
      predominant growth inhibition in cases of high CaR expression or activation, but
      prevailing stimulation of proliferation in cases of low CaR expression.

PMID- 11454017
TI  - Changes of gallbladder and gastric dynamics in patients with acute hepatitis A.
AB  - Transient alterations of gallbladder morphology and dynamics have been reported
      in patients with during acute hepatitis A. The presence of dyspepsia also
      suggests involvement of gastric motility. During a 60-day follow-up, we
      investigated gallbladder and gastric motility in relation to dyspepsia in acute
      viral hepatitis A patients. Twenty patients were assessed at referral (day 0) and
      at days 7, 21, 42 and 60 and compared with 20 healthy volunteers. Gallbladder
      morphology and motility and gastric motility were assessed in the fasting and
      postprandial period by functional ultrasonography using a liquid test meal.
      Dyspeptic symptoms were scored. At day 0, fasting gallbladder volume was 5.9 +/-
      1.3 mL, 32.6 +/- 4.6 mL, and 21.5 +/- 1.9 mL (mean +/- SE) in patients with
      gallbladder sludge (n = 7), without sludge (n = 13) and controls, respectively (P
      < 0.05 in sludge vs. no sludge and controls; P < 0.05 in no sludge vs. controls,
      ANOVA). Small fasting gallbladder volume in patients with sludge increased and
      sludge disappeared within 7 days. At day 0, patients with sludge also had
      increased thickness of fasting gallbladder wall and increased serum transaminase
      levels compared with patients without sludge and controls. Gallbladder
      contraction was similar in patients and controls. However, patients had delayed
      gastric emptying, which positively correlated with dyspepsia score. Gallbladder
      morphological changes observed in the acute phase of hepatitis A are transient
      and are associated with hepatocellular damage. Gastric emptying is delayed during
      the first week of disease and is associated with dyspeptic symptoms.

PMID- 11454018
TI  - Homocysteine in breast cyst fluid.
AB  - BACKGROUND: Elevated plasma homocysteine concentrations have been reported in a
      variety of carcinoma, including those of the breast. The risk of breast cancer is
      higher in patients suffering from gross cystic disease. The breast cyst fluid
      contains unusual amounts of low- and high- molecular substances, including
      steroid hormones and their conjugates. The present study was undertaken to find
      out the presence of homocysteine in the fluid filling the cysts and have its
      concentration compared with other thiols, levels of Na+/K+ ratio and steroid
      hormones. Materials and methods Fourteen women suffering from gross cystic
      disease were enrolled in this study. Cystic concentrations of homocysteine (Hcy),
      cysteine (Cys), cysteinylglycine (Cys-Gly) and glutathione (GSH) were determined
      by high performance liquid chromatography, with fluorescence detection; estradiol
      (E2), progesterone, allopregnanolone and pregnenolone sulfate (PregS) by RIA
      methods. RESULTS: Mean levels of Hcy, Cys, Cys-Gly, Na+/K+, E2 and PregS in the
      fluid filling the breast cysts were significantly higher than the corresponding
      plasma concentrations. In addition, a negative correlation was found between
      cystic Hcy and the Na+/K+ ratio (Rs = -0.72, P = 0.003) and positive correlations
      between cyst Hcy and estradiol (Rs = 0.64, P = 0.018) and Hcy and PregS (Rs =
      0.60, P = 0.025). Conclusion The study provides the first evidence of thiol
      concentrations in the breast cyst fluid. The finding of a negative correlation
      between homocysteine and the Na+/K+ ratio support the idea that the homocysteine
      concentration in breast cysts might be used clinically as a marker for the
      development of breast cancer disease.

PMID- 11454019
TI  - The cryoglobulins: an overview.
AB  - Cryoglobulins are cold-precipitable immunoglobulins associated with a number of
      infectious, autoimmune and neoplastic disorders. Their appearance along with
      rheumatoid factor (RF) can be considered a normal event in the clearance of
      immune complexes and rarely produces any symptoms. The association between
      hepatitis C virus (HCV) and mixed cryoglobulinemia (MC) has been rendered evident
      since the recognition of serological markers of HCV infection. There is thus
      every reason to suppose that direct or indirect involvement of B cells on the
      part of the HCV results in their persistent stimulation, clonal expansion and
      release of molecules with RF activity. The formation of RF/IgG immune complexes
      is the key pathogenetic mechanism. The close correlation between HCV infection
      and MC also throws new light on the interpretation of autoimmune phenomena in the
      course of viral infection and on the close link between autoimmune diseases and
      lymphoproliferative disorders. The higher risk of non-Hodgkin's lymphoma (NHL)
      displayed by HCV positive subjects, especially in the Mediterranean basin,
      suggests that the HCV's chronic lymphoproliferative drive may progress towards
      frank lymphoid neoplasia. The presence of MC does not represent an in situ or
      'occult' NHL, because recent evidences indicate that none of the clones
      interpreted as predominant displays the molecular features of a true neoplastic
      process. The cryoglobulinemic syndrome is probably the consequence of pathogenic
      noxae that act upon the immune system of a host in which regulation of the
      peripheral T cell response appears to be in some way altered.

PMID- 11454020
TI  - Peripheral blood T-cell responses to pyruvate dehydrogenase complex in primary
      biliary cirrhosis: role of antigen-presenting dendritic cells.
AB  - Patients with primary biliary cirrhosis (PBC) are usually characterized by the
      presence of antibody to pyruvate dehydrogenase complex (PDC) in the sera and PDC
      specific T cells in the liver. However, most of the patients with PBC do not show
      peripheral blood T cells response to PDC. In this study, we re-evaluated the
      peripheral blood T cell responses to PDC in PBC using antigen-presenting
      dendritic cells (DCs). Twenty-four patients with PBC (AMA-positive: 16; AMA
      negative: 8) and 13 normal controls were enrolled in the study. Peripheral blood
      mononuclear cells (PBMC) and highly enriched populations of T cells were
      stimulated with either only PDC or DCs plus PDC or PDC-pulsed DC plus PDC.
      Antibodies to different components of PDC were estimated by an immunoblotting
      technique. PBMC from only one out of ten AMA-positive PBC patients proliferated
      when cultured with only PDC. However, peripheral blood T cells from ten out of
      ten AMA-positive PBC patients and three out of ten AMA-negative PBC patients, but
      none of the five normal controls showed PDC-specific proliferation when cultured
      with PDC-pulsed DCs. Two of these three AMA-negative PBC patients, although
      negative for AMA, were positive for antibodies to other components of PDC. PDC
      specific T cells are present in the peripheral blood from most of the patients
      with PBC. This is the first report on the effectiveness of antigen-pulsed DCs for
      the elucidation of autoantigen-specific immune response in human autoimmune
      diseases.

PMID- 11454021
TI  - Phase-coupled oscillator models can predict hippocampal inhibitory synaptic
      connections.
AB  - What factors are responsible for propagating electrical activity in the
      hippocampus? Using an intact, isolated hippocampus preparation, it is possible to
      observe spontaneous delta (< or = 4 Hz) waves of rhythmic field potentials. These
      rhythmic potentials are inhibitory in nature, mediated by GABAergic inhibitory
      potentials originating from a population of principal neurons. They start in the
      ventro-temporal region and move longitudinally towards the dorso-septal region
      with a phase lag of approximately 10% between the extracellular recordings. We
      use the mathematical framework of phase-coupled oscillators (PCO) to gain some
      insight into the underlying network system. A chain of 15 nearest-neighbour
      bidirectionally coupled PCOs is used where each oscillator refers to a segment of
      the CA1 region of the hippocampus that can generate these slow field potentials.
      We find that ventro-dorsal delta waves exist if there is a dominance in coupling
      strength in one direction. Without a one-way coupling dominance, ventro-dorsal
      waves can still exist, but then the coupling strengths need to be much larger.
      The relationship between entrained and intrinsic frequencies and the variation of
      propagation speeds along the longitudinal axis can be used to determine which
      case applies. Currently available experimental data supports one of the cases,
      predicting that there is a stronger ventral to dorsal inhibitory effect.

PMID- 11454022
TI  - Modulation of glycine responses by dihydropyridines and verapamil in rat spinal
      neurons.
AB  - Although glycine receptors (GlyRs) are responsible for the main spinal inhibitory
      responses in adult vertebrates, in the embryo they have been reported to mediate
      depolarizing responses, which can sometimes activate dihydropyridine-sensitive L
      type calcium channels. However, these channels are not the only targets of
      dihydropyridines (DHPs), and we questioned whether GlyRs might be directly
      modulated by DHPs. By whole-cell recording of cultured spinal neurons, we
      investigated modulation of glycine responses by the calcium channel antagonists,
      nifedipine, nitrendipine, nicardipine and (R)-Bay K 8644, and by the calcium
      channel, agonist (S)-Bay K 8644. At concentrations between 1 and 10 microM, all
      these DHPs could block glycine responses, even in the absence of extracellular
      Ca2+. The block was stronger at higher glycine concentrations, and increased with
      time during each glycine application. Nicardipine blocked GABAA responses from
      the same neurons in a similar manner. In addition to their blocking effects,
      nitrendipine and nicardipine potentiated the peak responses to low glycine
      concentrations. Both effects of extracellular nitrendipine on glycine responses
      persisted when the drug was present in the intracellular solution. Thus, these
      modulations are related neither to calcium channel modulation nor to possible
      intracellular effects of DHPs. Another type of calcium antagonist, verapamil (10
      50 microM), also blocked glycine responses. Our results suggest that some of the
      effects of calcium antagonists, including the neuroprotective and anticonvulsant
      effects of DHPs, might result partly from their interactions with ligand-gated
      chloride channels.

PMID- 11454023
TI  - The KCl cotransporter, KCC2, is highly expressed in the vicinity of excitatory
      synapses in the rat hippocampus.
AB  - Immunocytochemical visualization of the neuron-specific K+/Cl- cotransporter,
      KCC2, at the cellular and subcellular level revealed an area- and layer-specific
      diffuse labelling, and a discrete staining outlining the somata and dendrites of
      some interneurons in all areas of the rat hippocampus. KCC2 was highly expressed
      in parvalbumin-containing interneurons, as well as in subsets of calbindin,
      calretinin and metabotropic glutamate receptor 1a-immunoreactive interneurons.
      During the first 2 postnatal weeks, an increase of KCC2 staining was observed in
      the molecular layer of the dentate gyrus, correlating temporally with the arrival
      of entorhinal cortical inputs. Subcellular localization demonstrated KCC2 in the
      plasma membranes. Immunoreactivity in principal cells was responsible for the
      diffuse staining found in the neuropil. In these cells, KCC2 was detected
      primarily in dendritic spine heads, at the origin of spines and, at a much lower
      level on the somata and dendritic shafts. KCC2 expression was considerably higher
      in the somata and dendrites of interneurons, most notably of parvalbumin
      containing cells, as well as in the thorny excrescences of CA3 pyramidal cells
      and in the spines of spiny hilar and stratum lucidum interneurons. The data
      indicate that KCC2 is highly expressed in the vicinity of excitatory inputs in
      the hippocampus, perhaps in close association with extrasynaptic GABAA receptors.
      A high level of excitation is known to lead to a simultaneous net influx of Na+
      and Cl-, as evidenced by dendritic swelling. KCC2 located in the same
      microenvironment may provide a Cl- extrusion mechanism to deal with both ion and
      water homeostasis in addition to its role in setting the driving force of Cl-
      currents involved in fast postsynaptic inhibition.

PMID- 11454024
TI  - Global motion integration in the cat's lateral posterior-pulvinar complex.
AB  - Our laboratory previously showed that thalamic neurons in an extrageniculate
      nucleus, the lateral posterior-pulvinar complex (LP-pulvinar) could perform
      higher-order neuronal operations that had until then only been attributed to
      higher-level cortical areas. To further assess the role of the thalamus in the
      analysis of complex percepts, we have investigated whether neurons in the LP
      pulvinar complex can signal the direction of motion of random-dot kinematograms
      wherein the individual elements of the pattern do not provide coherent motion
      cues. Our results indicate that a subset of LP-pulvinar cells can integrate the
      displacement of individual elements into a global motion percept and that their
      large receptive fields permit the integration of motion for elements separated by
      large spatial intervals. We also found that almost all of the global motion
      sensitive neurons were not systematically pattern-motion-selective when tested
      with plaid patterns. The results indicate that LP-pulvinar cells can perform the
      higher-level spatio-temporal integration required to detect the global
      displacement of objects in a complex visual scene, further supporting the notion
      that extrageniculate thalamic cells are involved in higher-order motion
      processing. Furthermore, these results provide some evidence that there may be
      specialized mechanisms for processing different types of complex motion within
      the LP-pulvinar complex.

PMID- 11454025
TI  - Sex hormones regulate the contribution of PKCepsilon and PKA signalling in
      inflammatory pain in the rat.
AB  - We have evaluated the contribution of differences in second messenger signalling
      to sex differences in inflammatory pain and its control by sex hormones. In
      normal male but not female rats, epinephrine-induced mechanical hyperalgesia was
      antagonized by inhibitors of protein kinase Cepsilon (PKCepsilon), protein kinase
      A (PKA) and nitric oxide synthetase (NOS). Similarly, in PKCepsilon knockout
      mice, a contribution of PKCepsilon to epinephrine-dependent mechanical
      hyperalgesia occurred in males only. In contrast, hyperalgesia induced by
      prostaglandin E2, in both females and males, was dependent on PKA and NO. In both
      sexes, inhibitors of mitogen-activated protein kinase/extracellular-signal
      related kinase kinase (MEK) inhibited epinephrine hyperalgesia. In gonadectomized
      females, the second messenger contributions to epinephrine hyperalgesia
      demonstrated the pattern seen in males. Administration of oestrogen to
      gonadectomized females fully reconstituted the phenotype of the normal female.
      These data demonstrate gender differences in PKCepsilon, PKA and NO signalling in
      epinephrine-induced hyperalgesia which are oestrogen dependent and appear to be
      exerted at the level of the beta-adrenergic receptor or the G-protein to which it
      is coupled.

PMID- 11454026
TI  - Modification of the pacemaker activity of vestibular neurons in brainstem slices
      during vestibular compensation in the guinea pig.
AB  - In the guinea pig, unilateral labyrinthectomy causes an immediate and severe
      depression of the spontaneous activity of the ipsilateral central vestibular
      neurons, which subsequently recovers completely within one week. A possible
      underlying mechanism could be an increase in the endogenous activity of the
      neurons deprived of their labyrinthine input. Here, we addressed this hypothesis.
      The endogenous activity of the neurons was assessed by their spontaneous activity
      recorded extracellularly in brainstem slices in the presence of a cocktail of
      neurotransmitter blockers (CNQX, D-APV, bicuculline and strychnine) which freed
      them from their main synaptic influences. The left medial vestibular nucleus
      (MVN) was explored in a very systematic way and strict methodological precautions
      were taken in order to validate comparisons between the numbers of spontaneously
      active neurons recorded in the MVN of distinct slices. In the presence of
      neurotransmitter antagonists, the mean number of spontaneously active neurons
      detected in a single MVN increased dramatically from 9.5 in slices from control
      guinea pigs to 26.3 in slices from animals labyrinthectomized on the left side
      one week beforehand. The mean firing rate of the recorded neurons also increased
      from 7.5 +/- 5.6 spikes/s in slices from control animals to 12.3 +/- 7.6 spikes/s
      in slices from guinea pigs labyrinthectomized one week beforehand. These results
      show that deprivation of the vestibular neurons of their labyrinthine input
      caused a change in the deprived neurons themselves. They suggest that an increase
      in pacemaker activity might be a factor responsible for the restoration of
      spontaneous activity in the vestibular neurons after labyrinthectomy.

PMID- 11454027
TI  - Neuropeptide Y alters sedation through a hypothalamic Y1-mediated mechanism.
AB  - Neuropeptide Y (NPY) has been reported to profoundly influence and regulate brain
      circuits involved in a number of behaviours, like anxiety, alcohol intake, pain
      and energy homeostasis. Here we show that NPY increases sedation induced by
      different types of anaesthetics through interactions with the Y1 receptor.
      Consistently, in Y1-/- (homozygote knockout) mice NPY does not potentiate the
      pentobarbital-induced sedation. Similar results were obtained for avertin but not
      for ketalar- (NMDA antagonist) induced sedation. Local microinjection of NPY
      exhibited the strongest potentiating effect on pentobarbital-induced sedation in
      the posterior hypothalamic area and Y1 expression was found in the dorsal
      premammillary and medial part of medial mammillary nuclei. These results show
      that Y1 is essential for NPY-induced enhancement of sedation and place this
      activity of NPY in the posterior hypothalamic area, a region of the brain
      previously implicated in the regulation of the wake-sleep cycle.

PMID- 11454028
TI  - Control of secretion by mitochondria depends on the size of the local [Ca2+]
      after chromaffin cell stimulation.
AB  - In chromaffin cells, plasma membrane calcium (Ca2+) channels and mitochondria
      constitute defined functional units controlling the availability of Ca2+ nearby
      exocytotic sites. We show here that, when L-/N-type Ca2+ channels were inhibited
      with nisoldipine and omega-conotoxin GVIA, cytosolic [Ca2+] ([Ca2+]c) peaks
      measured in fura-4F-loaded cells were reduced by 36%; however, mitochondrial Ca2+
      uptake was unaffected and secretion was potentiated by protonophores as in
      control cells. By contrast, when non L-type Ca2+ channels were inhibited with
      omega-conotoxin MVIIC, [Ca2+]c peaks induced by high K+ were reduced by 73%,
      mitochondrial Ca2+ uptake was abolished, and secretion was not modified by
      protonophores. However, if Ca2+ entered only through L-type channels activated by
      FPL64176, high K+ stimulation induced fast mitochondrial Ca2+ uptake and
      catecholamine secretion was strongly increased and potentiated by protonophores.
      These results confirm the close association of catecholamine secretion to
      mitochondrial Ca2+ uptake, and indicate the sharp threshold of local [Ca2+]c
      (about 5 microM) required for triggering fast mitochondrial Ca2+ uptake that is
      able to modulate secretion. The entry of Ca2+ through L-type channels generated
      local [Ca2+]c increases just below that, inducing little mitochondrial Ca2+
      uptake unless FPL64176 was present. By contrast, Ca2+ entry through P/Q-type
      channels fully activated mitochondrial Ca2+ uptake. Control of secretion by
      mitochondria therefore depends critically on the ability of the stimulus to
      create large local [Ca2+]c microdomains.

PMID- 11454029
TI  - Gamma amino butyric acid (GABA) immunoreactivity in the vestibular nuclei of
      normal and unilateral vestibular neurectomized cats.
AB  - Recent neurochemical investigations of the central vestibular pathways have
      demonstrated that several neurotransmitters are involved in various operations
      required for stabilizing posture and gaze. Neurons of the vestibular nuclei (VN)
      receive GABAergic inhibitory afferents, and GABAergic neurons distributed
      throughout the vestibular complex are implicated in inhibitory vestibulo-ocular
      and vestibulo-spinal pathways. The aim of this study was to analyse the
      modifications of GABA immunoreactivity (GABA-ir) in the cat VN after unilateral
      vestibular neurectomy (UVN). Indeed, compensation of vestibular deficits is a
      good model for studying adult central nervous system (CNS) plasticity and the
      GABAergic system is involved in CNS plasticity. We studied GABA-ir by using a
      purified polyclonal antibody raised against GABA. Light microscopic preparations
      of thin (20 microm) sections of cat VN were used to quantify GABA-ir by an image
      analysing system measuring GABA-positive punctate structures and the number of
      GABA-positive neurons. Both the lesioned and intact sides were analysed in three
      populations of UVN cats killed at different times after injury (1 week, 3 weeks
      and 1 year). These data were compared to those collected in normal unlesioned and
      sham-operated cats. Results showed a spatial distribution of GABA-ir in the
      control cats that confirmed previous studies. GABA-ir neurons, fibres and nerve
      terminals were scattered in all parts of the VN. A higher concentration of GABA
      positive neurons (small cells) was detected in the medial and inferior VN (MVN
      and IVN) and in the dorsal part of the lateral VN (LVNd). A higher level of GABA
      positive punctate structures was observed in the MVN and in the prepositus
      hypoglossi (PH) nucleus. Lesion-induced changes were found at each survival time.
      One week after injury the number of GABA-positive neurons was significantly
      increased in the MVN, the IVN and the dorsal part of the LVN on the lesioned side
      and in the ventral part of the LVN on the intact side. One year later a bilateral
      increase in GABA-positive neurons was detected in the MVN whilst a bilateral
      decrease was observed in both the SVN and the ventral part of the LVN. Changes in
      the GABA-staining varicosities did not strictly coincide with the distribution of
      GABA-ir cells, suggesting that GABA-ir fibres and nerve terminals were also
      modified. One week and later after injury, higher GABA-staining varicosities were
      seen unilaterally in the ipsilateral MVN. In contrast, bilateral increases (in
      PH) and bilateral decreases (in SVN and the ventral part of the LVN) were
      recorded in the nearly (3 weeks) or fully (1 year) compensated cats. At this
      stage GABA-staining varicosities were significantly increased in the lesioned
      side of the MVN. These findings demonstrate the reorganization of the GABAergic
      system in the VN and its possible role in recovery process after UVN in the cat.
      The changes seen during the acute stage could be causally related to the VN
      neuron deafferentation, contributing to the static vestibular deficits. Those
      found in the compensated cats would be more functionally implicated in the
      dynamic aspects of vestibular compensation.

PMID- 11454030
TI  - Sound lateralization during passive whole-body rotation.
AB  - The effect of passive whole-body rotation about the earth-vertical axis on the
      lateralization of dichotic sound was investigated in human subjects. Pure-tone
      pulses (1 kHz; 0.1 s duration) with various interaural time differences were
      presented via headphones during brief, low-amplitude rotation (angular
      acceleration 400 degrees/s2; maximum velocity 90 degrees/s; maximum displacement
      194 degrees ). Subjects made two-alternative forced-choice (left/right)
      judgements on the acoustic stimuli. The auditory median plane of the head was
      shifted opposite to the direction of rotation, indicating a shift of the
      intracranial auditory percept in the direction of rotation. The mean magnitude of
      the shift was 10.7 micros. This result demonstrates a slight, but significant,
      influence of rotation on sound lateralization, suggesting that vestibular
      information is taken into account by the brain for accurate localization of
      stationary sound sources during natural head and body motion.

PMID- 11454031
TI  - Forced swimming stimulates the expression of vasopressin and oxytocin in
      magnocellular neurons of the rat hypothalamic paraventricular nucleus.
AB  - Previous studies have shown that a 10-min forced swimming session triggers the
      release of both vasopressin and oxytocin into the extracellular fluid of the
      hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) in rats. At the
      same time oxytocin, but not vasopressin, was released from the axon terminals
      into the blood. Here we combined forced swimming with in situ hybridization to
      investigate whether (i) the stressor-induced release of vasopressin and oxytocin
      within the PVN originates from parvo- or magnocellular neurons of the nucleus,
      and (ii) central release with or without concomitant peripheral secretion is
      followed by changes in the synthesis of vasopressin and/or oxytocin. Adult male
      Wistar rats were killed 2, 4 or 8 h after a 10-min forced swimming session and
      their brains processed for in situ hybridization using 35S-labelled
      oligonucleotide probes. As measured on photo-emulsion-coated slides, cellular
      vasopressin mRNA concentration increased in magnocellular PVN neurons 2 and 4 h
      after swimming (P < 0.05). Similarly, oxytocin mRNA concentration was
      significantly increased in magnocellular neurons of the PVN at 2 and 8 h (P <
      0.05). We failed to observe significant effects on vasopressin and oxytocin mRNA
      levels in the parvocellular PVN and in the SON. Taken together with results from
      previous studies, our data suggest that magnocellular neurons are the predominant
      source of vasopressin and oxytocin released within PVN in response to forced
      swimming. Furthermore, in the case of vasopressin, central release in the absence
      of peripheral secretion is followed by increased mRNA levels, implying a refill
      of depleted somato-dendritic vasopressin stores. Within the SON, however, mRNA
      levels are poor indicators of the secretory activity of magnocellular neurons
      during stress.

PMID- 11454032
TI  - Functional topography of the human nonREM sleep electroencephalogram.
AB  - The sleep EEG of healthy young men was recorded during baseline and recovery
      sleep after 40 h of waking. To analyse the EEG topography, power spectra were
      computed from 27 derivations. Mean power maps of the nonREM sleep EEG were
      calculated for 1-Hz bins between 1.0 and 24.75 Hz. Cluster analysis revealed a
      topographic segregation into distinct frequency bands which were similar for
      baseline and recovery sleep, and corresponded closely to the traditional
      frequency bands. Hallmarks of the power maps were the frontal predominance in the
      delta and alpha band, the occipital predominance in the theta band, and the
      sharply delineated vertex maximum in the sigma band. The effect of sleep
      deprivation on EEG topography was determined by calculating the recovery/baseline
      ratio of the power spectra. Prolonged waking induced an increase in power in the
      low-frequency range (1-10.75 Hz) which was largest over the frontal region, and a
      decrease in power in the sigma band (13-15.75 Hz) which was most pronounced over
      the vertex. The topographic pattern of the recovery/baseline power ratio was
      similar to the power ratio between the first and second half of the baseline
      night. These results indicate that changes in sleep propensity are reflected by
      specific regional differences in EEG power. The predominant increase of low
      frequency power in frontal areas may be due to a high 'recovery need' of the
      frontal heteromodal association areas of the cortex.

PMID- 11454033
TI  - Long-lasting hippocampal potentiation and contextual memory consolidation.
AB  - In order to ascertain whether there are hippocampal electrophysiological
      modifications specifically related to memory, exploratory activity and emotional
      stress, extracellular electrical activity was recorded in hippocampal slices
      prepared from the brains of male adult rats. Several groups of animals were
      employed: (i) rats which had freely explored the experimental apparatus (8 min
      exposure); (ii) rats which had been subjected, in the same apparatus, to a fear
      conditioning paradigm training entailing the administration of aversive
      electrical footshocks (8 min exposure); (iii) rats to which the same number of
      aversive shocks had been administered in the same apparatus, but temporally
      compressed so as to make difficult the association between painful stimuli and
      the apparatus (30 s exposure); (iv) naive rats never placed in the apparatus.
      Half of the rats from each treatment group were used for retrieval testing and
      the other half for hippocampal excitability testing. The conditioned freezing
      response was exhibited for no less than 4 weeks. Hippocampal excitability was
      measured by means of input-output curves (IOC) and paired-pulse facilitation
      curves (PPF). Retrieval testing or brain slices preparation were performed at
      increasing delays after the training sessions: immediately afterwards or after 1,
      7 or 28 days. Only the rats subjected to the fear conditioning training exhibited
      freezing when placed again in the apparatus (retrieval testing). It was found
      that IOCs, with respect to naive rats, increased in the conditioned animals up to
      the 7-day delay. In free exploration animals the IOCs increased only immediately
      after the training session. In all other rats no modification of the curves was
      observed. IOC increases do not appear to imply presynaptic transmitter release
      modifications, because they were not accompanied by PPF modifications. In
      conclusion, a clear-cut correlation was found between the increase in
      excitability of the Schaffer collateral-CA1 dendrite synapses and freezing
      response consolidation.

PMID- 11454034
TI  - Feeding suppression by fibroblast growth factor-1 is accompanied by selective
      induction of heat shock protein 27 in hypothalamic astrocytes.
AB  - It has been suggested that fibroblast growth factor (FGF)-1 serves as a
      physiological satiety factor in the hypothalamus, although the molecular
      mechanism underlying such a function is poorly understood. To gain additional
      insight into this issue, we used a Sendai virus (SeV) gene expression system in
      rats to explore genes differentially expressed subsequent to expression of FGF-1.
      Using cDNA arrays, we determined that infusion of FGF-1/SeV into one lateral
      ventricle induced selective expression of heat shock protein (HSP) 27 in the
      hypothalamus. Whereas FGF-1 expression was restricted to the ependymal cell layer
      of the cerebral ventricles, HSP27 was more widely expressed in astrocytes
      residing in the surrounding periventricular region. Similarly, infusion of FGF-1
      polypeptide into a lateral ventricle induced dose-dependent HSP27 expression in
      periventricular astrocytes surrounding the third ventricle, with maximum mRNA
      levels being attained 6 h after infusion. This induction of HSP27 was accompanied
      by a significant suppression of feeding behaviour. Interestingly, suppression of
      feeding caused by intracerebro ventricular infusion of ciliary neurotrophic
      factor was also accompanied by induction of HSP27 in periventricular astrocytes,
      but suppression of feeding caused by infusion of leptin was not. It therefore
      appears that suppression of feeding by FGF-1 is accompanied by selective
      induction of HSP27 expression in hypothalamic astrocytes surrounding the third
      ventricle, and that this response may be a key component of the mechanism by
      which appetite is regulated by FGF-1.

PMID- 11454035
TI  - 'Arm-reaching' neurons in the parietal area V6A of the macaque monkey.
AB  - In previous experiments we have found that several cells of area V6A in the
      macaque superior parietal lobule were activated by small and stereotyped
      movements of the arms (C. Galletti, P. Fattori, D. F. Kutz & P. P. Battaglini,
      Eur. J. Neurosci., 1997, 9, 410). This behaviour was not accounted for by retinal
      information, nor by somatosensory inputs from the arms. We now want to
      investigate whether V6A neurons are modulated by purposeful movements aimed at
      reaching visual targets or targets located outside the field of view. V6A
      neuronal activity was collected while monkeys performed arm movements during an
      instructed-delay reaching task in darkness. The task required the animal to reach
      out for a visual target in the peripersonal space and to bring the hand back to
      its body. Quantitative analysis of neuronal activity carried out on 55 V6A
      neurons showed that: (i) the great majority of neurons (71%) was significantly
      modulated during the execution of arm movements; (ii) 30% of neurons were
      significantly modulated during preparation of reaching; and (iii) modulations
      during both execution and preparation of reaching occurred in the absence of any
      visual feedback and were not due to eye movements. V6A reach-related neurons
      could be useful in guiding the hand to reach its target with or without visual
      feedback.

PMID- 11454036
TI  - Design and characterization of a DNA-encoded, voltage-sensitive fluorescent
      protein.
AB  - Optical imaging of electrical activity has been suggested as a promising approach
      to investigate the multineuronal representation of information processing in
      brain tissue. While considerable progress has been made in the development of
      instrumentation suitable for high-speed imaging, intrinsic or extrinsic dye
      mediated optical signals are often of limited use due to their slow response
      dynamics, low effective sensitivity, toxicity or undefined cellular origin.
      Protein-based and DNA-encoded voltage sensors could overcome these limitations.
      Here we report the design and generation of a voltage-sensitive fluorescent
      protein (VSFP) consisting of a voltage sensing domain of a potassium channel and
      a pair of cyan and yellow emitting mutants of green fluorescent protein (GFP). In
      response to a change in transmembrane voltage, the voltage sensor alters the
      amount of fluorescence resonance energy transfer (FRET) between the pair of GFP
      mutants. The optical signals respond in the millisecond time-scale of fast
      electrical signalling and are large enough to allow monitoring of voltage changes
      at the single cell level.

PMID- 11454037
TI  - Phospholipase A2 mediates ischemic injury in the hippocampus: a regional
      difference of neuronal vulnerability.
AB  - Although it is well known that the hippocampal CA1 subfield is highly vulnerable
      to ischemic injury, cellular mechanisms leading to this neuronal degeneration are
      not fully understood. Using organotypic cultures of rat hippocampal slices, we
      determined whether phospholipase A2 (PLA2) is activated in response to ischemic
      conditions (OGD; oxygen and glucose deprivation). The PLA2 activity in the
      pyramidal cell layer increased immediately following a 35-min exposure to OGD,
      which was likely to be mediated by selective activation of cytosolic Ca2+
      dependent PLA2 subtype (cPLA2). This enhancement lasted for at least 24 h.
      Interestingly, no apparent increase was detected in the dentate gyrus. Twenty
      four hours after the OGD exposure, neuronal death was detected mainly in the CA1
      region of hippocampal slices. To examine whether the PLA2 activation is causally
      or protectively involved in the ischemic injury, we investigated the effect of
      pharmacological blockade of PLA2 on the OGD-induced neuronal death. The PLA2
      inhibitor bromophenacyl bromide efficiently prevented the cell death in a
      concentration-dependent manner. Similar results were obtained for the selective
      cPLA2 inhibitor AACOCF3. However, the Ca2+-independent PLA2 inhibitor bromoenol
      lactone and the secretory PLA2 inhibitor LY311727 were virtually ineffective.
      These results suggest that cPLA2 plays a causative role in the neuronal death
      following OGD exposure. Thus, the present study may provide novel therapeutic
      targets for the development of neuroprotective agents.

PMID- 11454038
TI  - Mitotic counting in surgical pathology: sampling bias, heterogeneity and
      statistical uncertainty.
AB  - Mitotic counting in surgical pathology: sampling bias, heterogeneity and
      statistical uncertainty Although several articles on the methodological aspects
      of mitotic counting have been published, the effects of macroscopic sampling and
      tumour heterogeneity have not been discussed in any detail. In this review the
      essential elements for a standardized mitotic counting protocol are described,
      including microscopic calibration, specific morphological criteria, macroscopic
      selection, counting procedure, effect of biological variation, threshold, and the
      setting of an area of uncertainty ('grey area'). We propose that the use of a
      standard area for mitotic quantification and of a grey area in mitotic counting
      protocols will facilitate the application of mitotic counting in diagnostic and
      prognostic pathology.

PMID- 11454039
TI  - Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with
      emphasis on its value in differentiating squamous cell carcinomas from other
      epithelial tumours.
AB  - AIMS: The tissue distribution of cytokeratin 14 (CK14) in epithelial neoplasms is
      not well defined. We have evaluated 435 cases of epithelial neoplasm of various
      origins with cytokeratin 14 monoclonal antibody with special attention to
      possible use in differential diagnosis. METHODS AND RESULTS: Immunohistochemistry
      (ABC-HRP method) was performed for detection of CK14. We found that the
      expression of cytokeratin 14 was generally restricted to: (i) the majority of
      cases of squamous cell carcinoma regardless of origin (67/74) and degree of
      differentiation; (ii) neoplasms with focal squamous differentiation, including
      endometrial, and ovarian adenocarcinoma, malignant mesothelioma and transitional
      cell carcinoma; (iii) thymoma (8/8); (iv) myoepithelial components of salivary
      gland pleomorphic adenoma (3/4); and (v) oncocytic neoplasms, including thyroid
      Hurthle cell adenoma (1/1) and salivary gland Warthin's tumour (2/2). CONCLUSION:
      CK14 protein is a useful marker in differential diagnosis of squamous cell
      carcinomas.

PMID- 11454040
TI  - Oncocytic papillary carcinoma with lymphoid stroma (Warthin-like tumour) of the
      thyroid: a distinct entity with favourable prognosis.
AB  - AIMS: We report the clinicopathological and immunohistochemical characteristics
      of 12 cases of a recently recognized entity, oncocytic papillary thyroid
      carcinoma (PC) with lymphoid stroma (Warthin-like tumour). METHODS AND RESULTS:
      The cases were retrieved from the surgical pathology files of our departments.
      There were 11 female patients and one male patient; they ranged in age from 45 to
      85 years (mean 64.2 years). The immunohistochemical profile demonstrated
      positivity of tumour cells for cytokeratins, thyroglobulin, Leu-M1 and anti
      mitochondrial antigen. S100 protein-positive stromal dendritic/Langerhans cells
      were uniformly present. Polymerase chain reaction, in situ hybridization, and
      immunohistochemistry for Epstein-Barr virus (EBV) detection revealed no
      significant positive signal. MIB-1 labelling index was low, compatible with that
      of 'classical' PC. CONCLUSIONS: Warthin-like tumour is a rare variant of PC,
      occurring predominantly in elderly women. Its histological features are distinct
      and well recognizable, differentiating this tumour from a more aggressive tall
      cell variant of PC. The apparent indolent behaviour seems to be consistent with
      the presence of dendritic/Langerhans cells and with low proliferative activity. A
      possible role of EBV in pathogenesis of this lesion was not proven. Further
      studies are necessary to determine the prognosis and metastatic potential of this
      neoplasm.

PMID- 11454041
TI  - Follicular adenoma with papillary architecture: a lesion mimicking papillary
      thyroid carcinoma.
AB  - AIMS: The purpose of this study was to investigate the significance of 'benign'
      encapsulated follicular thyroid nodules with papillary structures. METHODS AND
      RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with
      papillary structures and nuclear features not diagnostic of papillary thyroid
      carcinoma (PTC) were obtained. All cases were reviewed with particular attention
      to nuclear features (fine chromatin pattern, optical clearing, grooves and
      inclusions). Representative sections were submitted for measurement of the
      maximum diameter of 200 round or nearly round nuclei and for immunostaining for
      MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered
      optically clear nuclei or nuclear grooves in less than 30% of total neoplastic
      cells. They were grouped in the category of thyroid nodules with limited nuclear
      features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The
      other 12 cases had fine or coarse chromatin, but lacked other features of nuclei
      in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller
      than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity
      for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied
      from negative or focally weak to diffusely moderate reactivity. Ret oncogene
      protein immunostaining showed focal and weak reactivity in one case and was
      negative in other cases of the study. Clinical follow-up from 6 months to 15
      years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures
      in the study cases are unlikely to represent degenerative changes due to their
      proliferative activity. In view of (i) the encapsulation and the uniformity of
      the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and
      HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the
      absence or insufficiency of nuclear criteria for the diagnosis of PTC and the
      absence of lymph node metastasis in all study cases, we believe that these
      lesions represent the papillary variant of follicular adenoma. Recognition of
      this pathological entity is important to avoid an over-diagnosis of PTC.

PMID- 11454042
TI  - The 'dark nucleus' and disruptions of follicular architecture: possible new
      histological aids for the diagnosis of the follicular variant of papillary
      carcinoma of the thyroid.
AB  - AIMS: In order to facilitate the diagnosis of malignancy in solitary thyroid
      nodules which are non-invasive low-grade tumours, i.e. follicular variant of
      papillary carcinoma (FVPC) for which few histological discriminators exist, a
      search was made for additional diagnostically useful histological features.
      METHODS AND RESULTS: Haematoxylin and eosin (H & E)-stained sections of 70
      resection specimens of solitary thyroid nodules were re-evaluated by a panel of
      three pathologists, and their consensus and original diagnoses compared. In
      addition, H & E- and periodic acid-Schiff-stained sections were evaluated for
      various histological features and sections were stained by various
      immunohistochemical markers to evaluate their discriminative powers. The above
      features were also assessed in a group of 24 papillary carcinomas of the thyroid
      (PTCs) associated with regional metastases. The finding of 'Orphan Annie eye'
      nuclei was the best indicator of malignancy, and was closely related to the
      presence of nuclear grooves and cells with dense, dark nuclei. In addition,
      distorted follicular architectural features, i.e. 'interconnecting cell masses'
      and 'fenestration', were also significant indicators of malignancy. Tumours
      diagnosed as FVPCs had a significantly lower incidence of associated lymph node
      metastases than the classical PTCs. CONCLUSIONS: The use of optically clear
      nuclei as a diagnostic criterion when found only focally may not be sufficiently
      stringent in distinguishing FVPCs from follicular adenomas. When classical
      histological indicators of malignancy are equivocal, the diagnosis of FVPC may be
      facilitated by the above-mentioned features.

PMID- 11454043
TI  - Reduced expression of p21WAF1 is an indicator of malignant behaviour in anal
      carcinomas.
AB  - AIMS: p21 and p27 protein expression were examined in a comparatively large
      series of patients with squamous cell carcinoma of the anal canal and compared
      with clinical and histopathological data (tumour stage, nodal status and
      differentiation). METHODS AND RESULTS: We analysed the expression of p21 and p27
      protein in 94 anal carcinomas by immunohistochemistry. Nuclear p21 and p27
      staining were detected in 71% (67/94) and 75% (71/94) of the cases, respectively.
      There was no significant association between p27 staining and tumour stage, nodal
      status or overall survival. We observed that negative p21 immunoreactivity was
      significantly associated with poorly differentiated anal carcinomas. Furthermore,
      a shorter overall survival for patients with no p21 protein expression was seen.
      CONCLUSIONS: Our data indicate that p21 levels, but not p27 expression, may be a
      useful predictor of survival in patients with anal carcinomas.

PMID- 11454044
TI  - Vascular smooth muscle cells and pericytes express MMP-1, MMP-9, TIMP-1 and type
      I procollagen in inflammatory bowel disease.
AB  - AIMS: Matrix metalloproteinases (MMPs) are involved in tissue remodelling, which
      is one of the important aspects of inflammatory disease. To assess the balance
      between the matrix degradation and production, we analysed the in situ expression
      of MMP-1, -3, -8 and -9, tissue inhibitor of metalloproteinases (TIMP)-1 and -2,
      and type I procollagen (PC-I) in inflammatory bowel disease. METHODS AND RESULTS:
      Immunohistochemistry using frozen sections was performed in 17 patients with
      ulcerative colitis (UC) and 16 with Crohn's disease (CD). In both UC and CD, MMPs
      and TIMPs were expressed by inflammatory cells as well as by fibroblastic cells
      most prominently in actively inflamed areas in ulcer bases, but sparsely in
      intact inflamed mucosa in both UC and CD. In UC, inflamed mucosa with erosions
      expressed these substances focally. Fibroblasts also expressed PC-I. We
      identified that vascular smooth muscle cells of venules in ulcer bases expressed
      MMP-1 and -9, TIMP-1 and PC-I. These venules also expressed E-selectin, a cell
      adhesion molecule to facilitate the leucocyte extravasation, and vascular
      endothelial growth factor (VEGF) receptor 2, consistent with their property of
      newly formed vessels. CONCLUSIONS: Our results suggest that MMPs are involved in
      the tissue remodelling, angiogenesis and promotion of leucocyte extravasation in
      the actively inflamed area in the ulcer base in both UC and CD. MMP-1 expression
      in the mucosa may be related to the initial step of ulceration in UC. Therapeutic
      manipulation of extracellular matrix turnover would be an effective therapy to
      alleviate active inflammation and accelerate ulcer healing.

PMID- 11454045
TI  - Use of a monoclonal antibody against Lafora bodies for the immunocytochemical
      study of ground-glass inclusions in hepatocytes due to cyanamide.
AB  - AIMS: Ground-glass inclusions (GGIs) in hepatocytes are known to be associated
      with cyanamide treatment in patients with alcohol dependency. The purpose of this
      study was to assess the reactivity of a monoclonal antibody (MAb) raised against
      polyglucosan and to detect early events in GGI formation. METHODS AND RESULTS:
      Formalin-fixed paraffin-embedded liver tissues from four patients treated with
      cyanamide were used. Sections were stained with haematoxylin and eosin and
      periodic acid-Schiff with and without diastase digestion, and were
      immunohistochemically stained with the MAb. For electron microscopic study,
      routinely processed liver tissue from one patient was examined with conventional
      and immunoelectron microscopy with use of the MAb. All specimens from the four
      cyanamide-treated patients contained GGIs in the cytoplasm of hepatocytes, and
      these GGIs reacted intensely with the MAb. Fully developed GGIs contained various
      organelles, whereas early ones consisted primarily of glycogen granules and
      dilated smooth endoplasmic reticulum. In immunoelectron microscopic preparations,
      gold particles were located within GGIs, and the immunolabelled organelles
      appeared to be glycogen granules. CONCLUSIONS: This novel MAb is useful for the
      detection of GGIs caused by cyanamide. Our results support the idea that GGI
      formation may result from specific abnormalities in glucose metabolism.

PMID- 11454046
TI  - Predictive value of liver cell dysplasia for development of hepatocellular
      carcinoma in patients with non-cirrhotic and cirrhotic chronic viral hepatitis.
AB  - AIMS: Hepatocellular carcinoma (HCC) frequently develops in patients with chronic
      viral hepatitis, especially in the cirrhotic stage. We retrospectively studied
      whether the presence of the putative preneoplastic lesions large liver cell
      dysplasia (LLCD) and/or small liver cell dysplasia (SLCD) in a needle liver
      biopsy of these patients are a risk factor for the development of HCC. METHODS
      AND RESULTS: The presence of LLCD and SLCD in the needle liver biopsy taken at
      the initial work-up of 115 patients with chronic hepatitis B or C was assessed
      retrospectively. LLCD and SLCD were present in the initial biopsy of,
      respectively, 35 (30%) and 25 patients (22%). During a mean follow-up of 107
      months, 16 patients (14%) developed HCC and this occurred significantly more
      frequently in patients with cirrhosis, age > or = 55 years, LLCD or SLCD.
      Cirrhosis and LLCD were independent risk factors for HCC development.
      CONCLUSIONS: Our findings indicate that the presence of LLCD in a needle liver
      biopsy of patients with viral-induced chronic liver disease is an independent
      risk factor for the development of HCC. If these results are confirmed, the
      presence of LLCD can be used to identify a subgroup of patients at high risk for
      HCC requiring more intensive screening.

PMID- 11454047
TI  - Accuracy of frozen section diagnoses of breast lesions after introduction of a
      national programme in mammographic screening.
AB  - AIMS: By introducing mammography screening programmes, the size of the detected
      breast lesions became smaller and the histopathological interpretation problems
      greater. The study's aim was to analyse the risks and possible limitations of the
      frozen section method. METHODS AND RESULTS: Frozen section consultations of
      breast lesions (n=559) 2 years before and 6 years after launching a national
      mammographic screening programme in 1992 were evaluated in regard of the
      benign/malignant ratio, tumour size, preoperative frozen section results and
      final permanent section diagnoses. The breast frozen section examinations of 1990
      compared with those from 1998 declined from 70.7% (299/423) to 62.2% (260/418) (P
      < 0.01), the benign/malignant ratio from 1.09 to 0.54 (P < 0.0001), the rate of
      the conclusive, correct frozen section diagnoses from 96.3% to 91.9% (P < 0.03).
      The sensitivity dropped from 92.3% to 87.6%, the negative predictive value from
      95.7% to 88.3%, whereas the negative likelihood ratio rose from 0.08 to 0.12. The
      'small' (< or = 10 mm) invasive breast carcinomas increased from 14.2% to 22.3%
      (P < 0.01) and the 'in situ' carcinomas from 2.1% to 6.6% (P < 0.05).
      CONCLUSIONS: The declining sizes of breast tumours (< or = 10 mm), especially
      from radiologically detected lesions and sometimes without a macroscopic
      correlate, create new limitations and changing indications in the
      histopathological interpretation. Considering the performance of new diagnostic
      methods (i.e. large core needle biopsies), frozen sections of surgical specimens
      should not be the primary diagnostic procedure for breast lesions and should be
      performed only after other preoperative methods have failed.

PMID- 11454048
TI  - A new method of margin evaluation in breast conservation surgery using an
      adjustable mould during fixation.
AB  - AIMS: We have developed a new method of breast resection margin assessment in
      quadrantectomy using an adjustable mould to prevent the three-dimensional
      specimen from distorting during fixation. METHODS AND RESULTS: The new method has
      been applied to 10 consecutive quadrantectomies (six invasive duct carcinomas,
      four duct carcinoma in situ with or without microinvasion). The precise
      configuration of the fixed specimen enabled pathologists to examine the side
      slices, the 5 mm thick slices cut parallel to the flat lateral margins of the
      specimen, permitting the separation of margin evaluation from tumour
      characterization. Eight cases with negative margins by our method would also be
      negative by assessment of inked margins since the margin widths were estimated to
      be from 5 to 30 mm (average 16.3 mm); two cases with positive margins would also
      be positive by inked margins. CONCLUSIONS: Our new method was as reliable as the
      inked margins employing sequential slicing of the entire tissue, although it
      reduced the number of blocks by more than half in invasive carcinomas. A further
      advantage of this method is that the accuracy in margin evaluation is not
      influenced by the extent of tumour sampling. In addition, our system can pinpoint
      the positive margins facilitating re-excision to obtain tumour-free margins.

PMID- 11454049
TI  - Two relatively distinct patterns of ameloblastoma: an anti-apoptotic
      proliferating site in the outer layer (periphery) and a pro-apoptotic
      differentiating site in the inner layer (centre).
AB  - AIMS: This study was performed to determine the apoptotic behaviour of
      ameloblastomas by analysing the role of bcl-2 family proteins in ameloblastomas
      and the location of terminally apoptotic cells in the ameloblastoma epithelial
      tissues. METHODS AND RESULTS: For immunohistochemistry, tissue sections of 32
      patients were treated with an antigen-retrieval METHOD: Primary antibodies
      against the apoptosis-related proteins, bcl-2, bcl-X, bax, and bak were applied.
      Besides immunohistochemistry, Western blotting and TUNEL were also performed.
      Most of the outer layer cells were predominantly stained by the bcl-2 antibody,
      while most of the inner layer cells were stained by antibodies against the
      apoptosis-modulating proteins, bax and bak. Among the bcl-2 family, bcl-2 was the
      most ubiquitously expressed protein in ameloblastomas, while bcl-X was expressed
      in the greatest concentrations. The major bcl-X protein was bcl-XL. Some of the
      inner layer cells entered the terminal apoptotic stage, which were revealed by
      TUNEL. The acanthomatous areas over-expressed the apoptosis-modulating proteins,
      especially bak. CONCLUSIONS: Ameloblastoma has much more apoptosis-inhibiting
      protein than the apoptosis-modulating protein. Ameloblastoma has two relatively
      distinct patterns, an anti-apoptotic proliferating site in the outer layer
      (periphery) and a pro-apoptotic differentiating site in the inner layer (centre).
      The acanthomatous area, which was stained strongly by bak antibody and contained
      numerous terminally apoptotic cells, was considered as the differentiated area.

PMID- 11454050
TI  - Diagnostic gold standard for soft tissue tumours: morphology or molecular
      genetics?

PMID- 11454051
TI  - Symptomatic diffuse colonic lipomatosis in Proteus syndrome.

PMID- 11454052
TI  - Deciduoid pleural mesothelioma.

PMID- 11454053
TI  - Lymphoepithelioma-like carcinoma of ureter.

PMID- 11454054
TI  - Nitric oxide and bone.
AB  - Nitric oxide (NO) is a free radical which has important effects on bone cell
      function. The endothelial isoform of nitric oxide synthase (eNOS) is widely
      expressed in bone on a constitutive basis, whereas inducible NOS is only
      expressed in response to inflammatory stimuli. It is currently unclear whether
      neuronal NOS is expressed by bone cells. Pro-inflammatory cytokines such as IL-1
      and TNF cause activation of the iNOS pathway in bone cells and NO derived from
      this pathway potentiates cytokine and inflammation induced bone loss. These
      actions of NO are relevant to the pathogenesis of osteoporosis in inflammatory
      diseases such as rheumatoid arthritis, which are characterized by increased NO
      production and cytokine activation. Interferon gamma is a particularly potent
      stimulator of NO production when combined with other cytokines, causing very high
      concentrations of NO to be produced. These high levels of NO inhibit bone
      resorption and formation and may act to suppress bone turnover in severe
      inflammation. The eNOS isoform seems to play a key role in regulating osteoblast
      activity and bone formation since eNOS knockout mice have osteoporosis due to
      defective bone formation. Other studies have indicated that the NO derived from
      the eNOS pathway acts as a mediator of the effects of oestrogen in bone. eNOS
      also mediates the effects of mechanical loading on the skeleton where it acts
      along with prostaglandins, to promote bone formation and suppress bone
      resorption. Pharmacological NO donors have been shown to increase bone mass in
      experimental animals and preliminary evidence suggests that these agents may also
      influence bone turnover in man. These data indicate that the L-arginine/NO
      pathway represents a novel target for therapeutic intervention in the prevention
      and treatment of bone diseases.

PMID- 11454055
TI  - The contributions of T-cell anergy to peripheral T-cell tolerance.

PMID- 11454056
TI  - Upregulation of CD4 on CD8+ T cells: CD4dimCD8bright T cells constitute an
      activated phenotype of CD8+ T cells.
AB  - Aside from an intermediate stage in thymic T-cell development, the expression of
      CD4 and CD8 is generally thought to be mutually exclusive, associated with helper
      or cytotoxic T-cell functions, respectively. Stimulation of CD8+ T cells,
      however, induces the de novo expression of CD4. We demonstrate that while
      superantigen (staphylococcal enterotoxin B, SEB) and anti-CD3/CD28 costimulation
      of purified CD8+ T cells induced the expression of CD4 on CD8+ T cells by 30 and
      17%, respectively, phytohaemagglutinin (PHA) stimulation did not induce CD4
      expression on purified CD8+ T cells but significantly induced the expression of
      both CD4 on CD8 (CD4dimCD8bright) and CD8 on CD4 (CD4brightCD8dim) T cells in
      unfractionated peripheral blood mononuclear cells (PBMC). The level of the PHA
      mediated induction of CD4dimCD8bright and CD4brightCD8dim was at 27 and 17%,
      respectively. Depletion of CD4+ T cells from PBMC abrogated this PHA-mediated
      effect. Autologous CD4+ and CD8+ T-cell co-cultures in the presence of PHA
      induced this CD4dimCD8bright T-cell expression by 33%, demonstrating a role for
      CD4 cells in the PHA-mediated induction of the double positive cells. The
      induction of CD4dimCD8bright was independent of a soluble factor(s). Phenotypic
      analysis of CD4dimCD8bright T cells indicated significantly higher levels of
      CD95, CD25, CD38, CD69, CD28, and CD45RO expression than their CD8+CD4-
      counterparts. CD4dimCD8bright T cells were also negative for CD1a expression and
      were predominantly T-cell receptor (TCR) alphabeta cells. Our data demonstrate
      that CD4dimCD8bright T cells are an activated phenotype of CD8+ T cells and
      suggest that CD4 upregulation on CD8+ T cells may function as an additional
      marker to identify activated CD8+ T cells.

PMID- 11454057
TI  - Systematic characterization of human CD8+ T cells with natural killer cell
      markers in comparison with natural killer cells and normal CD8+ T cells.
AB  - We investigated the function of CD56+ CD8+ T cells (CD56+ T cells) and CD56-
      CD57+ CD8+ T cells (CD57+ T cells; natural killer (NK)-type T cells) and compared
      them with those of normal CD56- CD57- CD8+ T cells (CD8+ T cells) and CD56+ NK
      cells from healthy volunteers. After the stimulation with immobilized anti-CD3
      antibodies, both NK-type T cells produced much larger amounts of interferon-gamma
      (IFN-gamma) than CD8+ T cells. Both NK-type T cells also acquired a more potent
      cytotoxicity against NK-sensitive K562 cells than CD8+ T cells while only CD56+ T
      cells showed a potent cytotoxicity against NK-resistant Raji cells. After the
      stimulation with a combination of interleukin (IL)-2, IL-12 and IL-15, the IFN
      gamma amounts produced were NK cells > or = CD56+ T cells > or = CD57+ T cells >
      CD8+ T cells. The cytotoxicities against K562 cells were NK cells > CD56+ T cells
      > or = CD57+ T cells > CD8+ T cells while cytotoxicities against Raji cells were
      CD56+ T cells > CD57+ T cells > or = CD8+ T cells > or = NK cells. However, the
      CD3-stimulated proliferation of both NK-type T cells was smaller than that of
      CD8+ T cells partly because NK-type T cells were susceptible to apoptosis. In
      addition to NK cells, NK-type T cells but not CD8+ T cells stimulated with
      cytokines, expressed cytoplasmic perforin and granzyme B. Furthermore, CD3
      stimulated IFN-gamma production from peripheral blood mononuclear cells (PBMC)
      correlated with the proportions of CD57+ T cells in PBMC from donors. Our
      findings suggest that NK-type T cells play an important role in the T helper 1
      responses and the immunological changes associated with ageing.

PMID- 11454058
TI  - Influence of CD4 or CD8 deficiency on collagen-induced arthritis.
AB  - The role of T cells in the mouse collagen-induced arthritis (CIA) model for
      rheumatoid arthritis is not clarified, and different results have been reported
      concerning the role of CD4 and CD8 T cells. To address this issue, we have
      investigated B10.Q mice deficient for CD4 or CD8. The mice lacking CD4 were found
      to be less susceptible to disease, but not completely resistant, whereas the CD8
      deficiency had no significant impact on the disease. No difference in the
      development of late occurring relapses was noted. Interestingly, the CD4
      deficient mice had a severely reduced response to the glycosylated form of the
      immunodominant type II collagen (CII) 256-270 peptide whereas the response to the
      non-glycosylated peptide was not significantly different. Furthermore, CD4
      deficient mice had lower antibody responses to CII, explaining the lower disease
      susceptibility. In comparison with previously reported results, it is apparent
      that the lack of CD4 molecules has a different impact on CIA if present on
      different genetic backgrounds, findings that could possibly be related to the
      occurrence of different disease pathways of CIA in different mouse strains.

PMID- 11454059
TI  - Characterization of self-T-cell response and antigenic determinants of U1A
      protein with bone marrow-derived dendritic cells in NZB x NZW F1 mice.
AB  - Systemic lupus erythematosus (SLE) is characterized by the existence of a
      heterogeneous group of autoantibodies directed against nuclear intact structures,
      such as nucleosomes and small nuclear ribonucleoproteins (snRNPs). Autoantibodies
      against snRNPs are of special interest because they are detectable in the
      majority of SLE patients. Although the B-cell antigenic determinants have been
      well characterized, very limited data have been reported in regard to the T-cell
      epitopes of snRNPs. Furthermore, several studies have demonstrated that
      determination of the auto-T-cell epitopes recognized by freshly isolated T cells
      is difficult from unprimed lupus mice when self-antigen-pulsed B cells or
      macrophages are used as antigen-presenting cells (APCs) in vitro. In the present
      study, we showed a novel approach for determining the auto-T-cell epitopes, using
      bone marrow-derived dendritic cells (BMDCs) pulsed with the murine U1A protein -
      an immunodominant antigen of the U1 snRNPs - which is capable of activating
      freshly isolated T cells from unprimed (NZB x NZW) F1 (BWF1) mice in vitro. The T
      cell epitope area was found to be located at the C-terminus of U1A, overlapping
      the T-cell epitope of human U1A that has been reported in human SLE.
      Identification of the autoreactive T-cell epitope(s) in snRNPs will help to
      elucidate how reciprocal T-B determinant spreading of snRNPs emerges in lupus.
      The results presented here also indicate that it is feasible to use this approach
      to further explore strategies to design immunotherapy for patients with lupus.

PMID- 11454060
TI  - The role of donor T cells for target organ injuries in acute and chronic graft
      versus-host disease.
AB  - Donor T cells are crucial for target organ injury in graft-versus-host disease
      (GVHD). We examined the effects of donor T cells on the target organs using a
      parent-into-F1 model of acute and chronic GVHD. Donor T cells showed engraftment
      in the spleen, small intestine and liver of mice with acute GVHD, causing typical
      GVHD pathology in these organs. Interferon-gamma and Fas ligand expression were
      up-regulated, and host lymphocytes were depleted in the target organs of these
      mice. In contrast, donor T cells did not show engraftment in the small intestine
      of mice with chronic GVHD, and no GVHD pathology was observed in this organ.
      However, both donor T-cell engraftment and GVHD pathology were observed in the
      spleen and liver of chronic GVHD mice, along with the up-regulation of
      interleukin-4 (IL-4) and IL-10 expression plus the expansion of host lymphocytes
      such as splenic B cells and hepatic natural killer (NK) 1.1+ T cells. Donor anti
      host cytotoxic T-lymphocyte activity was observed in spleen cells from mice with
      acute GVHD, but not in spleen cells from mice with chronic GVHD. Transplantation
      of Fas ligand-deficient (gld) spleen cells did not induce host lymphocyte
      depletion in target organs. These results indicate that donor T cells augment
      type 1 T helper immune responses and deplete the host lymphocytes from target
      organs mainly by Fas-mediated pathways in acute GVHD, while donor T cells augment
      type 2 T helper immune responses and expand host splenic B cells and hepatic
      NK1.1+ T cells in chronic GVHD.

PMID- 11454061
TI  - Endocytosis and recycling of the complex between CD23 and HLA-DR in human B
      cells.
AB  - The presentation of extremely low doses of antigen to T cells is enhanced by
      immunoglobulin E (IgE)-dependent antigen focusing to CD23, the low-affinity
      receptor for IgE, expressed on activated B cells. CD23 contains a C-type lectin
      domain in its extracellular sequence and a targeting signal for coated pits,
      required for endocytosis, in its cytoplasmic sequence. CD23 is non-covalently
      associated with the major histocompatibility complex class II antigen, human
      leucocyte antigen HLA-DR, on the surface of human B cells, but the fate of this
      complex following endocytosis is unknown. To answer this question we have
      labelled these proteins on the surface of RPMI 8866 B cells and traced their
      route through the cytoplasm. Endocytosis mediated by anti-CD23 antibodies (BU38
      and MHM6) led to the loss of CD23 from the cells. Endocytosis mediated by an
      antibody to HLA-DR (CR3/43) or an antigen-IgE complex (NP-BSA-anti-NP IgE),
      however, led to recycling of the HLA-DR-CD23 complex to the cell surface on a
      time scale (3-6 hr) consistent with the recycling of HLA-DR in antigen
      presentation. Along the latter pathway CD23 label was observed in cytoplasmic
      organelles that resembled the 'compartments for peptide loading' or 'class II
      vesicles' described by previous authors. Two features of the recycling process
      may contribute to the efficiency of antigen presentation. Peptide exchange may be
      facilitated by the proximity of HLA-DR and antigen in peptide loading
      compartments of the endosomal network. The return of CD23 with HLA-DR to the cell
      surface may then help to stabilize specific B-cell-T-cell interactions,
      contributing to T-cell activation.

PMID- 11454062
TI  - Calmodulin protects cells from death under normal growth conditions and mitogenic
      starvation but plays a mediating role in cell death upon B-cell receptor
      stimulation.
AB  - Calmodulin (CaM) is the main intracellular Ca2+ sensor protein responsible for
      mediating Ca2+ triggered processes. Chicken DT40 lymphoma B cells express CaM
      from the two genes, CaMI and CaMII. Here we report the phenotypes of DT40 cells
      with the CaMII gene knocked out. The disruption of the CaMII gene causes the
      intracellular CaM level to decrease by 60%. CaMII-/- cells grow more slowly and
      die more frequently as compared to wild type (wt) cells but do not exhibit
      significant differences in their cell cycle profile. Both phenotypes are more
      pronounced at reduced serum concentrations. Upon stimulation of the B-cell
      receptor (BCR), the resting Ca2+ levels remain elevated after the initial
      transient in CaMII-/- cells. Despite higher Ca2+ resting levels, the CaMII-/-
      cells are partially protected from BCR induced apoptosis indicating that CaM
      plays a dual role in apoptotic processes.

PMID- 11454063
TI  - Differing processing requirements of four recombinant antigens containing a
      single defined T-cell epitope for presentation by major histocompatibility
      complex class II.
AB  - A set of predictive rules governing the likelihood of generating a particular
      peptide-major histocompatibility complex (MHC) class II complex from an intact
      antigen has not been fully elucidated. We investigated the influence of
      positional and structural constraints in the region of the epitope by designing a
      set of recombinant antigens that each contained the well-characterized T-cell
      epitope moth cytochrome c (MCC) (88-103), which is specifically recognized by the
      monoclonal antibody (mAb) D4 when complexed with H-2Ek. Our model antigens
      contained MCC(88-103) either peripherally, at or towards the C-terminus, or
      internally. Their abilities to bind directly to soluble H-2Ek, and the extent of
      D4 epitope formation from them by antigen processing-competent and -incompetent
      cell lines, were determined. Here we report that three of these four antigens
      yielded MCC(88-103)/H-2Ek complexes independently of the conventional MHC class
      II antigen-processing and presentation pathway, and in each case the epitope was
      carried peripherally; two bound directly as intact proteins, probably as a result
      of spatial separation of the epitope from the major globular domain, and one was
      processed to peptide by a cell-surface protease. One protein, which carried the
      epitope inserted into an internal loop, acted as a conventional processing
      dependent MCC(88-103) delivery vehicle. Thus, this epitope has different
      presentation requirements depending on its context. These antigens constitute a
      panel whose framework could be modified to further define predictive rules for
      antigen processing for presentation through the different MHC class II complex
      generating pathways.

PMID- 11454064
TI  - The use of human CD68 transcriptional regulatory sequences to direct high-level
      expression of class A scavenger receptor in macrophages in vitro and in vivo.
AB  - Macrophages (Mphi) play a key role in innate and acquired immunity. The study of
      Mphi biology has been hampered by the absence of suitable gene regulatory
      sequences for the overexpression of heterologous genes in Mphi. The human CD68
      gene encodes a glycoprotein that is expressed in monocytes and Mphi, and
      therefore represents an attractive candidate gene for the generation of a Mphi
      specific gene-targeting vector. A transgene expression cassette that combines 2.9
      kb of CD68 5' flanking sequence with the 83-bp first intron (IVS-1) of the CD68
      gene, directed high-level, long-lasting expression of class A human scavenger
      receptor (hSR-A) isoforms in the murine Mphi cell line, RAW-264. By using this
      CD68 expression cassette to generate Mphi cell lines that overexpress a soluble
      secreted form of the extracellular portion of type I human SR-A, we were able to
      purify significant quantities of this protein and show its ability to inhibit SR
      A-mediated endocytosis. Analysis of two independent lines of transgenic mice that
      expressed type III human SR-A under the control of the CD68 gene sequences
      revealed transgene mRNA expression in elicited Mphi populations and in mouse
      tissues in a pattern that was consistent with Mphi-specific gene targeting. These
      data show that CD68 transcriptional regulatory sequences can be used to direct
      high-level transgene expression in Mphi in vitro and in vivo.

PMID- 11454065
TI  - Nitric oxide protects cultured rheumatoid synovial cells from Fas-induced
      apoptosis by inhibiting caspase-3.
AB  - Nitric oxide (NO) is elevated in the synovial fluids and sera of patients with
      rheumatoid arthritis (RA) and is thought to be an important proinflammatory
      mediator in the rheumatoid synovium. To test the hypothesis that NO might
      modulate the apoptosis-inducing signal pathway, we investigated the effects of NO
      on rheumatoid synovial-cell apoptosis induced by Fas ligation with anti-Fas
      antibody. Pretreatment of synovial cells with the NO donor S-nitro-N
      acetylpenicillamine (SNAP) prevented the Fas-mediated induction of apoptosis. The
      activation of caspase-3 was required to mediate Fas-induced synovial cell
      apoptosis. The NO donor SNAP inhibited Fas-induced caspase-3 activation in
      rheumatoid synovial cells. However, NO did not interrupt Fas-induced caspase-8
      cleavage or subsequent cytochrome c release into the cytosol in rheumatoid
      synovial cells. These data indicate that NO prevents apoptosis in rheumatoid
      synovial cells by directly inhibiting caspase-3 activation. Thus, we propose that
      NO interferes with cell death signal transduction and may contribute to
      rheumatoid synovial cell proliferation by inhibiting induction of apoptosis.

PMID- 11454066
TI  - Interleukin-12 primes CD4+ T cells for interferon-gamma production and protective
      immunity during Mycobacterium avium infection.
AB  - Interleukin-12 (IL-12) is a crucial cytokine for the generation of a protective
      immune response against Mycobacterium avium infection. In contrast to infected
      control mice, IL-12-deficient mice were unable to control bacterial proliferation
      and their spleen T cells were almost unresponsive in vitro to specific antigens
      of M. avium. Susceptibility of mice deficient in IL-12 was similar to that of
      interferon-gamma (IFN-gamma)-deficient mice. These data indicate a crucial role
      of IL-12 in the development of a T-cell population able to produce IFN-gamma and
      to mediate protection against M. avium infection. Treatment of M. avium-infected
      mice with IL-12 induced CD4+ T cells with enhanced capacity to produce IFN-gamma
      as well as to confer increased protection against M. avium.

PMID- 11454067
TI  - Interleukin-6 regulates the phenotype of the immune response to a tuberculosis
      subunit vaccine.
AB  - We investigated the role of interleukin-6 (IL-6) in the development of the immune
      response to a subunit vaccine against tuberculosis consisting of the culture
      filtrate proteins of Mycobacterium tuberculosis emulsified in the adjuvant
      dimethyldioctadecylammonium bromide (DDA). C57Bl/6 mice immunized with this
      vaccine developed a strong T helper 1 (Th1) response characterized by an
      increased production of interferon-gamma (IFN-gamma) secreted by CD4+ T cells.
      Neutralization of IL-6 during in vivo priming resulted in marked reduction in the
      ability of T cells to secrete IFN-gamma and IL-2 and to proliferate. IL-6 gene
      disrupted mice primed with the vaccine showed a decrease in the number of IFN
      gamma-producing cells and an increase in IL-4-secreting cells as compared to
      control mice. In contrast, neutralization of IL-6 during a boost of the vaccine
      in previously primed mice did not affect the development of IFN-gamma-producing
      cells but still increased the number of IL-4-producing cells. Our work shows that
      IL-6 plays a major role in the priming but not in the later expression of a Th1
      response to a tuberculosis vaccine.

PMID- 11454068
TI  - Maternal tolerance is not critically dependent on interleukin-4.
AB  - Pregnant animals can generate and maintain immune responses to fetal antigens.
      This however, does not usually lead to fetal loss. At least two types of immune
      response are recognized. T helper type 1 (Th1) responses support the generation
      of cellular cytotoxicity. In contrast, Th2-type responses support the production
      of non-cytotoxic antibody and suppress the Th1-type. One attempt to explain why
      the fetus is not generally rejected has been to suggest that during pregnancy Th2
      type responses are dominant. These responses rely heavily on interleukin-4 (IL-4)
      for both functions. This work focuses on maternal immunity to the male antigen H
      Y, which is expressed in male fetuses. When injected with male spleen cells,
      female mice of certain strains mount a cytotoxic immune response to H-Y. However,
      pregnant females immunized in this way do not deliver litters with fewer males.
      To help delineate the possible role of IL-4 in such maternal tolerance, female
      mice genetically deficient in IL-4 were studied. The results show that: (1)
      deficiency in maternal IL-4 does not affect fertility, (2) deficiency in IL-4 is
      not associated with selective loss of male offspring in unimmunized mice, (3)
      pregnancy does not obliterate anti-H-Y reactivity in immunized mice and (4)
      maternal immunity to H-Y in the absence of IL-4 does not result in loss of male
      offspring. The results suggest that IL-4-dependent Th2-type responses are not
      critical to maternal tolerance. Other cytokines must be examined for their role
      in this phenomenon.

PMID- 11454069
TI  - Streptococcal inhibitor of complement (SIC) inhibits the membrane attack complex
      by preventing uptake of C567 onto cell membranes.
AB  - Streptococcal inhibitor of complement (SIC) was first described in 1996 as a
      putative inhibitor of the membrane attack complex of complement (MAC). SIC is a
      31 000 MW protein secreted in large quantities by the virulent Streptococcus
      pyogenes strains M1 and M57, and is encoded by a gene which is extremely
      variable. In order to study further the interactions of SIC with the MAC, we have
      made a recombinant form of SIC (rSIC) in Escherichia coli and purified native M1
      SIC which was used to raise a polyclonal antibody. SIC prevented reactive lysis
      of guinea pig erythrocytes by the MAC at a stage prior to C5b67 complexes binding
      to cell membranes, presumably by blocking the transiently expressed membrane
      insertion site on C7. The ability of SIC and clusterin (another putative fluid
      phase complement inhibitor) to inhibit complement lysis was compared, and found
      to be equally efficient. In parallel, by enzyme-linked immunosorbent assay both
      SIC and rSIC bound strongly to C5b67 and C5b678 complexes and to a lesser extent
      C5b-9, but only weakly to individual complement components. The implications of
      these data for virulence of SIC-positive streptococci are discussed, in light of
      the fact that Gram-positive organisms are already protected against complement
      lysis by the presence of their peptidoglycan cell walls. We speculate that MAC
      inhibition may not be the sole function of SIC.

PMID- 11454070
TI  - A new objective method for scoring human sperm hyperactivation based on head axis
      angle deviation.
AB  - The aims of the present study were, first to develop a new method for evaluating
      sperm hyperactivation (HA) based on sperm head axis angle deviation, and second
      to apply this method in scoring selected sperm populations during capacitation.
      This was made possible by improving our original superimposed image analysis
      system (SIAS). The new option on the system enables us to determine the real
      angular deviation of the entire head in successive superimposed frames. The
      entire procedure for each spermatozoon requires 10-20 sec, according to the
      frame/rate utilized. A clear cut-off between the values of hyperactivated,
      transitional and non-hyperactivated spermatozoa was found at 11 and 21
      frames/sec. However, at 6 frames/sec, a partial overlap between the three classes
      was found. We defined sperm activity as follows. At 11 frames/sec,
      hyperactivated: angle sum > or = 405 degrees; transitional: 200 degrees < or =
      angle sum < 405 degrees. At 21 frames/sec, hyperactivated: angle sum > or = 760
      degrees; transitional: 350 degrees < or = angle sum < 760 degrees. The results,
      in agreement with previous research, show the peaks of activity at 3 h, dropping
      to a minimum at 6 h. This phenomenon was significantly more evident in fertile
      compared with subfertile semen samples.

PMID- 11454071
TI  - Aneuploidy in spermatozoa of infertile men with teratozoospermia.
AB  - Recent studies have shown that aneuploidy in spermatozoa of infertile men with
      poor semen quality is increased. The purpose of this study was to determine
      whether poor sperm morphology is associated with the incidence of spermatozoa
      with numerical chromosome abnormalities. Semen samples from 20 infertile
      teratozoospermic men were studied using multicolour fluorescence in situ
      hybridization (FISH). Men were divided into four groups according to the
      proportion of normal sperm morphology: infertile men with <10% (group A, n=7), 10
      19% (group B, n=6), and 20-29% (group C, n=7) of morphologically normal
      spermatozoa, and controls (group D, n=5) with > or =30% normal forms. Two
      hybridizations were performed. All the samples were analysed using probes for
      chromosomes 1 and 7 and, in addition, in group A and in controls with normal
      semen parameters probes for chromosomes X, Y and 18 were also used. Ten thousand
      spermatozoa were scored per hybridization. Severely teratozoospermic men (<10%
      normal forms) had significantly higher frequency of disomy 7, 18, YY, XY and
      diploidy in their spermatozoa when compared with controls. The results suggest
      that poor sperm morphology is associated with numerical chromosome abnormalities
      of spermatozoa. Severely teratozoospermic men may be at an increased risk of
      producing aneuploid offspring.

PMID- 11454072
TI  - Differential effect of hyperthyroidism on rat epididymal glycosidases.
AB  - The impact of hyperthyroidism on epididymal glycosidases was studied in albino
      rats. Hyperthyroidism was induced in Wistar rats aged 30 days by daily injection
      of T4 (25 microg/100 g body weight/day intramuscularly) for 30 or 60 days;
      control rats were injected with vehicle (alkaline saline, pH 7.8). One set of
      hyperthyroid rats was reverted to euthyroid status by withdrawing T4 treatment
      after 30 days of hyperthyroidism. To asses the direct effect of thyroid hormone
      on epididymal hexosaminidases, caput, corpus and cauda tissues were stimulated
      with 25, 50 or 100 ng/mL T3 for 24 h, after an initial culture of 24 h. The
      activity of beta-glucosidase decreased in caput, corpus and cauda epididymis of
      hyperthyroid rats. beta-Galactosidase activity increased in the caput epididymis
      irrespective of the duration of hyperthyroidism. While a similar decrease
      occurred in the corpus and cauda epididymis in the 30 day hyperthyroid group, an
      opposite trend was observed in 60 day hyperthyroid rats. Caput beta-N
      acetylglucosaminidase activities increased at both time points, whereas activity
      decreased in the corpus and cauda in 30 day, but increased in 60 day hyperthyroid
      rats. Hyperthyroidism consistently increased caput and corpus beta-N
      acetylgalactosaminidase activity irrespective of the duration. Cauda epididymal
      beta-N-acetylgalactosaminidase activity was decreased in 30 day and increased in
      60 day hyperthyroid rats. Hyperthyroidism induced changes in caput beta
      galactosidase, beta-N-acetylgalactosaminidases, corpus beta-N
      acetylglucosaminidase and cauda beta-N-acetylgalactosaminidase which were
      irreversible while the remaining actvities were brought back to normal when T4
      treatment was withdrawn. In vitro studies showed that T3 stimulates epididymal
      hexosaminidases (beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase)
      irrespective of the dose. These data suggest that thyroid hormones have a
      specific and direct influence on glycosidases in specific regions of the
      epididymis.

PMID- 11454073
TI  - The motility of demembranated human spermatozoa is inhibited by free calcium ion
      activities of 500 nmol/L or more.
AB  - A number of studies have demonstrated that high calcium ion activities inhibit
      sperm motility, but little is known about the effect of different calcium
      activities close to the physiological range. Therefore, we investigated whether
      raising calcium activities within the submicromolar range would inhibit the
      motility of demembranated human spermatozoa. Spermatozoa were demembranated with
      Triton X-100 and motility was measured objectively by computer assisted semen
      analysis. Motility, reactivated by 1 mol adenosine 5'-triphosphate (AlphaTauP)/L,
      was short lived, with maximum activity only sustained for about 1 min.
      Reactivated motility was not affected by 50 micromol cAMP/L. The amplitude of
      lateral head displacement was significantly greater at room temperature than at
      37 degrees C, but there were no significant differences between the percentage of
      sperm motile or their velocity at the two temperatures. The calcium buffer 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) at 1 mmol/L was
      included in the demembranation-reactivation medium, and free calcium ion
      activities were calibrated using the fluorescent calcium probe Fura-2. Calcium
      ion activities of > or =500 nmol/L significantly inhibited the percentage of
      demembranated-reactivated spermatozoa that were motile, and the velocity and
      lateral head displacement of these cells. The range of intracellular calcium
      activities in spermatozoa from 24 cryopreserved ejaculates was 110-534 nmol/L;
      roughly twice the value in fresh spermatozoa. Therefore, calcium ion activities
      in the range observed in cryopreserved spermatozoa can inhibit the activity of
      demembranated human spermatozoa.

PMID- 11454074
TI  - Assay of testicular angiotensin-converting enzyme activity in human spermatozoa.
AB  - The testicular isozyme of angiotensin-converting enzyme (ACE) is associated with
      male fertility. Spermatozoa from mice lacking ACE showed defects in transport
      within the oviducts and in binding to zonae pellucidae although the animals had
      normal sperm count, morphology and motility. In fact, unexplained infertility is
      difficult to be predicted by conventional parameters such as sperm count. We
      measured membrane testicular ACE activity in a sperm suspension in PBS and total
      testis ACE activity in spermatozoa by solubilization with Triton X-100. Total
      testis ACE activity and membrane testis ACE activity of the same subject were
      compared in 12 control subjects. We demonstrated that testicular ACE is stable in
      spermatozoa and the assay of testicular ACE activity is possible. Total
      testicular ACE activity was approximately twice the membrane testicular ACE
      activity in all of the subjects tested. The assay of testicular ACE activity in
      human spermatozoa could be a new method for the assessment of sperm function.

PMID- 11454075
TI  - A comparison of megestrol acetate, nandrolone decanoate and dietary counselling
      for HIV associated weight loss.
AB  - This randomized, prospective study compared three treatments, nandrolone
      decanoate (ND), megestrol acetate (MA) or dietary counselling, for managing human
      immunodeficiency syndrome (HIV) associated weight loss. It was centred on a
      Tertiary referral hospital, Sydney, Australia. Fifteen patients were randomized
      to receive ND (100 mg/fortnight), or MA (400 mg/day) or dietary counselling for
      12 weeks. Those patients randomized to dietary counselling were further
      randomized to receive nandrolone or megestrol after completing the dietary
      counselling arm. Weight, fat free mass (FFM), percentage body fat mass (FM),
      dietary intake and appetite were assessed before commencing and at the completion
      of each treatment arm. Weight increased significantly in all treatment arms
      (dietary counselling 1.13 kg +/- 0.36, nandrolone 4.01 kg +/- 1.68, megestrol
      10.20 kg +/- 4.51, p < 0.05 paired t-test). FFM increased significantly in
      patients receiving ND (3.54 +/- 1.98 kg, p=0.001) and those receiving MA (2.76 +/
      0.55 kg, p=0.002), whereas the change in those receiving dietary counselling
      alone was not significant. Percentage body fat mass increased significantly only
      in those receiving MA (7.77 +/- 4.85%, p=0.049). The change in weight and
      percentage body fat mass was significantly greater in those receiving MA than the
      other two treatment arms. The increase in FFM was significantly greater in both
      the nandrolone and megestrol arms than the dietary counselling arm. It was
      concluded that ND and MA both resulted in an increase in FFM greater than dietary
      counselling alone. Megestrol produced a significantly greater increase in weight,
      percentage fat mass, intake and appetite than did the other two treatment arms,
      suggesting it may be the preferred agent, particularly in a palliative care
      setting in which weight, appetite and intake increase are desirable without
      regard to the composition of the body. The long-term use of these agents in
      people with HIV should be reviewed in the context of improved survival on highly
      active antiretroviral therapy regimens.

PMID- 11454076
TI  - Irrigation of the distal vas deferens during vasectomy: does it accelerate the
      post-vasectomy sperm-free rate?
AB  - A prospective, non-randomized, partially blinded, controlled trial was conducted
      to evaluate the efficacy of irrigation with normal saline solution (NSS) during
      no-scalpel vasectomy (NSV) compared with NSV alone in 62 men. In the NSS
      irrigation group, an Angiocath 24-gauge needle was inserted into the distal vas
      lumen, and 20 mL NSS solution was used to irrigate the vas manually on both
      sides. Post-operative follow-up included urine samples collected immediately and
      semen samples for sperm count at 2, 6 and 12 weeks post-vasectomy. The difference
      in the number of spermatozoa appearing in the post-vasectomy urine samples and
      the mean urine sperm count in both groups were significantly different ( p <
      0.0001 and p < 0.01, respectively). The numbers of post-operative ejaculations,
      the mean sperm concentration, and the number of patients who achieved sterility
      (defined as no motile spermatozoa in the ejaculate) in both groups at 2, 6 and 12
      weeks were similar ( p > 0.05). It is concluded that although irrigation of the
      distal vas with NSS was successful in removing a large number of spermatozoa from
      the tract, this procedure did not significantly accelerate the rate of achieving
      absence of motile spermatozoa in the ejaculate.

PMID- 11454077
TI  - Detection of progesterone receptors in human spermatozoa and their correlation
      with morphological and functional properties.
AB  - In previous reports, it has been demonstrated that progesterone (P) stimulates
      capacitation, hyperactivation of human sperm motility and initiates the acrosome
      reaction (AR). This last effect has been related to the presence of non-genomic
      receptors for the steroid, localized on the sperm head plasma membrane. These
      receptors can be detected after treating spermatozoa with the non-permeable
      conjugate Progesterone - 3-(O-carboxymethyl) oxime: bovine serum albumin
      fluorescein isothiocyanate (P-BSA-FITC). In the present study, the presence of
      progesterone receptors was determined in a selected sperm population with normal
      morphology and high progressive motility. In addition, other parameters such as
      the AR, hypo-osmotic swelling test, stability of chromatin and capacitating
      effect of P were evaluated. The percentage of P-BSA-FITC positive-spermatozoa
      present in the selected sperm population was higher than in total seminal
      spermatozoa. Furthermore, spermatozoa incubated with P showed a higher percentage
      motility and AR than did control spermatozoa. The HOS test indicated that
      membrane integrity of P-treated spermatozoa was not different to that found in
      the control sperm suspensions. Unexpectedly, the total sperm population treated
      with P showed a marked susceptibility to nuclear decondensation with reducing
      agents. According to these results, the selected sperm population of this study,
      able to respond to P, may be similar to that with good motility and normal
      morphology selected in the female reproductive tract, before fertilization.

PMID- 11454078
TI  - Cicatricial (scarring) alopecia.

PMID- 11454079
TI  - Cutaneous sarcoidosis.

PMID- 11454080
TI  - The interactions and role of epithelial cadherin and catenins in tumorigenicity.

PMID- 11454081
TI  - Morphology of glass fibers in electronics workers with fiberglass dermatitis--a
      scanning electron microscopy study.
AB  - BACKGROUND: Fiberglass is used as a reinforcement filler material in printed
      circuit boards (PCBs) which are widely used in the electronics industry. In a
      recent survey, we demonstrated that fiberglass dermatitis is the most common
      occupational dermatosis among electronics industry workers in Taiwan. Little is
      known, however, about the morphologic structures of the glass fibers which induce
      dermatitis. The purpose of this study was to assess the morphology of fiber
      spicules and to determine the relationship of this structure to fiberglass
      dermatitis. METHODS: Fourteen female patients with a diagnosis of fiberglass
      dermatitis were selected for study. The diagnosis was confirmed in all patients
      by positive skin stripping for glass fibers and matching with glass fibers from
      dust collected in work areas and from samples collected by scraping the edge of
      PCBs. Samples of collected glass fibers were analyzed by scanning electron
      microscopy (SEM). RESULTS: SEM of the fiberglass samples revealed that fibers
      were approximately 10 microm in diameter. In samples from both the edge of PCBs
      and from dust collected in work areas, SEM revealed that most of the fibers were
      in bundles of various sizes and lengths. All fibers collected from patients' skin
      by tape stripping showed a singular spicule, most had a sharp free end, and the
      lengths were in the range 50-150 microm . CONCLUSIONS: Singular glass fibers with
      a sharp free end and a length of 50-150 microm are most likely to induce
      fiberglass dermatitis.

PMID- 11454082
TI  - Overexpression of transforming growth factor-beta3 immunohistochemical staining
      in extramammary Paget's disease, but downregulated expression in Bowen's disease.
AB  - BACKGROUND: The role of transforming growth factor-beta (TGF-beta) in
      carcinogenesis is complex, with some reports indicating a tumor inhibition role
      and others indicating a tumor promotion role. In particular, TGF-beta3 is thought
      to play a key role in controlling epithelial homeostasis. Immunopositive p53 has
      been demonstrated in a variety of human malignant tumors and its role in
      oncogenesis and tumor progression is thought to be important. Extramammary
      Paget's disease (EPD) and Bowen's disease are skin cancers of unknown
      histogenesis. OBJECTIVE: To clarify the role of TGF-beta3 and p53 in EPD and
      Bowen's disease and to better understand the origin of these disorders. METHODS:
      Specimens were obtained from 12 patients with EPD and 12 patients with Bowen's
      disease seen at our clinic between 1993 and 2000. TGF-beta3 and p53
      immunohistochemical staining was performed. RESULTS: In three of the 12 EPD
      patients and five of the 12 Bowen's disease patients, positive p53 staining was
      detected. In contrast, TGF-beta3 overexpression was detected in all EPD patients,
      whereas downregulated TGF-beta3 expression was detected in all Bowen's disease
      patients. CONCLUSIONS: The present data suggest different roles for TGF-beta3 in
      abnormal epidermal cells in EPD and Bowen's disease. Thus, TGF-beta3 expression
      may be modulated differently via a p53-dependent or -independent pathway in the
      pathogenesis of EPD and Bowen's disease. Moreover, high TGF-beta expression
      appears to be a useful indicator of tumor activity in EPD.

PMID- 11454083
TI  - Clinical, histopathologic, and therapeutic aspects of subepidermal autoimmune
      bullous diseases with IgG on the floor of salt-split skin.
AB  - BACKGROUND: About 12% of patients with subepidermal autoimmune bullous disease
      and immunoglobulin G (IgG) at the dermal-epidermal junction present diseases
      other than bullous pemphigoid. MATERIALS AND METHODS: We report the clinical,
      histopathologic, and therapeutic aspects of eight cases of subepidermal bullous
      disorder with IgG on the floor of salt-split skin. RESULTS: A predominant
      neutrophilic infiltrate was detected in six of the eight patients. In one
      patient, the inflammatory infiltrate was neutrophilic and eosinophilic in the
      same proportion. A good response to dapsone alone or combined with prednisone was
      observed in six patients. CONCLUSIONS: The salt-split skin direct
      immunofluorescence test is useful for its diagnostic and therapeutic
      implications.

PMID- 11454084
TI  - Pigmentary changes of tinea versicolor in dark-skinned patients.
AB  - BACKGROUND: Tinea versicolor causes scaly macular lesions which vary in color
      from white to brown. In patients with dark skin, tinea versicolor is thought to
      have a tendency to be hypopigmented. This view has not been formally documented.
      OBJECTIVE: Our objective was to determine the pigmentary changes of lesions of
      tinea versicolor in patients with skin types IV and V. METHODS: One hundred cases
      of tinea versicolor in persons with skin types IV and V were studied. The
      pigmentary changes and their correlation with the age and sex of the patients and
      the duration, recurrence, site, and symptomatology of the lesions were
      determined. RESULTS: There was no correlation between the pigmentary variations
      of tinea versicolor and the type of skin, sex, and age of our patients or the
      duration, recurrence, site, and symptomatology of the lesions. CONCLUSIONS: In
      dark-skinned individuals, tinea versicolor does not tend to be significantly
      hypopigmented.

PMID- 11454085
TI  - Graves' disease presenting as elephantiasic pretibial myxedema and nodules of the
      hands.
AB  - A 67-year-old man presented with a 2-year history of asymptomatic, firm, multiple
      nodules and plaques and cerebriform hypertrophy of both lower legs and feet, and
      well-defined, skin-colored, firm nodules and tumors on both hands. He had been
      diagnosed as having Graves' disease 3 years previously, and had been treated with
      10 mg of methimazole and 100 microg of thyroxin (T4) daily for 2 years. Physical
      examination revealed nonpitting edema, flesh-colored to erythematous, firm,
      confluent, polypoid nodules and fissured plaques extending from the shins to the
      dorsa of both feet (Fig. 1), and round to oval, firm, skin-colored, walnut-to-egg
      sized tumors on all 10 fingers and the ulnar side of the dorsum of the right hand
      (Fig. 2). The thyroid gland was diffusely enlarged; however, there was no
      exophthalmos, and extraocular movements were normal. There was no weight loss,
      loss of appetite, tremor, heat intolerance, diarrhea, or fatigue. On laboratory
      evaluation, thyroid-stimulating hormone (TSH) had a markedly low titer of < 0.05
      microU/mL (normal: 0.4-5.0), and the TSH receptor antibody was extremely high at
      73.8% (normal: < 15%). Serum free triiodothyronine (T3), T4, antimicrosome, and
      antithyroglobulin antibodies were normal or negative. Skin biopsy samples from
      the shin and hand disclosed extensive mucin deposition throughout the dermis.

PMID- 11454086
TI  - A unique variant of Darier's disease.
AB  - A 45-year-old black woman presented with a chief complaint of an increasing
      number of "light spots" on her face, upper trunk, and legs. She had a 4-year
      history of a pruritic eruption on the dorsum of her hands. The eruption was
      particularly pruritic in the summer months. Other family members, including her
      sister and her daughters, reportedly had a similar dermatologic problem. The
      patient had been previously evaluated and biopsied by another dermatologist. The
      earlier biopsy was nondiagnostic, however, and she presented for further
      evaluation of this problem. On physical examination, the patient had
      hypopigmented macules along her jawline (Fig. 1), lateral neck, and upper chest.
      She had similar hypopigmented macules on her thighs. She had hyperkeratosis of
      the palmoplantar surface of her hands and feet. The dorsum of her hands had
      numerous coalescing, shiny, flat-topped, hypopigmented papules (Fig. 2), and
      several of her fingernails had distal, V-shaped notching. A punch biopsy from a
      papule on the dorsum of her hand was obtained. The epidermis had corps ronds
      present with focal areas of acantholysis above the basal layer (Fig. 3). The
      dermis had sparse, superficial, perivascular infiltrates composed of lymphocytes
      and histiocytes. These changes were consistent with our clinical diagnosis of
      Darier's disease (keratosis follicularis).

PMID- 11454087
TI  - Hard palate perforation: an unusual finding in paracoccidioidomycosis.
AB  - A 36-year-old black man presented to his dermatologist in May 1996 complaining of
      mucosal lesions in the mouth, as well as perforation of the hard palate. The
      lesions had started approximately 7 months before and had worsened gradually.
      Other complaints included odynophagia, dysphagia, mild dyspnea, and dry cough.
      The patient was in good general health, but reported a 3 kg weight loss over the
      previous semester. The hard and soft palate presented erythematous ulcers with a
      finely granulated base and irregular, but clearly defined margins. A perforation
      (diameter, 0.5 cm) of the hard palate was seen in the center of the ulcerated
      region (Fig. 1). Direct examination of 10% KOH cleared specimens showed typical
      double-walled, multiple budding yeast structures. Paracoccidioidomycosis (PCM)
      serologic reactions tested positive for double immunodiffusion (DI), complement
      fixation (CF) 1 : 256 and counterimmunoelectrophoresis (CIE) 1 : 128. Hematoxylin
      and eosin-stained sections of oral lesions showed an ulcer covered by a fibrous
      leukocytic crust, with a lymphoplasmacytic infiltrate, as well as multinuclear
      giant cells containing round bodies with a double membrane. Gomori-Grocott
      staining showed budding and blastoconidia suggestive of PCM. Lung computed
      tomography (CT) exhibited findings consistent with pulmonary PCM. Diagnosis of
      the chronic multifocal form of PCM with oral and pulmonary manifestations was
      established. Drug therapy was initiated with ketoconazole (KCZ) 200 mg twice
      daily, which led to clinical cure in approximately 2 months. Serum antibody
      values rose 30 days after institution of therapy (CIE 1 : 256; CF 1 : 512),
      peaking at day 60 (CIE 1 : 1024; CF 1 : 1024). Three months later the daily dose
      was reduced to 200 mg and titers declined slowly. The diameter of the perforation
      remained unchanged (Fig. 2). The hard palate perforation was corrected with a
      palatoplasty 27 months after initiation of drug therapy (Fig. 3). KCZ was
      discontinued when serologic cure was achieved after 34 months of treatment (DI
      weakly positive; CIE 1 : 8; CF not measurable). The patient was discharged 46
      months after the first visit.

PMID- 11454088
TI  - Association of juvenile xanthogranuloma with cafe-au-lait macules.
AB  - A 2-year-old boy was referred to the dermatology services for the evaluation of
      yellowish-brown raised lesions over the face of 3 months' duration. In addition,
      he had multiple asymptomatic hyperpigmented spots over the trunk, which his
      parents had noticed at the time of birth. His physical and mental milestones of
      development were normal. Apart from the cutaneous lesions, the child was
      otherwise well and there was no history of seizures. He was the only child born
      to nonconsanguineous parents. No family history of similar lesions was available.
      The boy weighed 14 kg, had a height of 88 cm, and a head circumference of 48 cm.
      General physical and systemic examination was normal. Cutaneous examination
      revealed multiple, yellowish-brown papules over the forehead, sides of the face,
      and shoulders. The papules measured 0.5-0.8 cm in diameter, were discrete, well
      defined, oval and flat topped without any surface changes (Fig. 1). Multiple cafe
      au-lait macules varying from 0.5 to 3.0 cm in diameter were present over the
      trunk (Fig. 2). There was no freckling in the axillary or the inguinal regions
      and no neurofibromas were present. A diagnosis of juvenile xanthogranuloma was
      considered. Complete blood counts, urine analysis, hepatic and renal function
      tests, and serum lipid levels were normal. A skin biopsy from a papule over the
      shoulder revealed a dense infiltrate in the dermis underlying a normal epidermis.
      The infiltrate was well demarcated and comprised lymphocytes, eosinophils, and
      foamy histiocytes along with Touton giant cells and proliferating fibroblasts.
      This confirmed the diagnosis of juvenile xanthogranuloma. The parents were
      informed about the benign and self-limiting nature of the disorder and were
      advised to bring the child for regular follow-up.

PMID- 11454089
TI  - Psoriasis vulgaris and acute guttate psoriasis in a family.
AB  - A 33-year-old man (Case 1) developed scaling and erythema on the extensor side of
      his extremities, head, and back, 3 years before his first visit to our hospital.
      The lesions spread out to form several plaques and became persistent (Fig. 1a).
      Serum antistreptolysin O (ASO) was within the normal range and a pharyngeal
      culture showed normal flora. Histologic findings were compatible with psoriasis
      vulgaris (Fig. 1b). Topical steroid therapy was effective; however, scaling and
      erythema persisted. The 8-year-old daughter (Case 2) of Case 1 had suffered
      severe tonsillitis 2 months prior to the skin eruptions. Numerous rain drop-like
      scaly papules appeared on her legs and generalized rapidly (Fig. 2a). Her tonsils
      were swollen and reddish. Streptococcus pyogenes was detected by pharyngeal
      smear. The ASO value was at a high level. Histologic examination showed slightly
      elongated rete ridges, focal lack of the granular layer, parakeratosis, mild
      spongiosis, and exostosis of neutrophils (Fig. 2b). She was diagnosed with acute
      guttate psoriasis. Administration of oral antimicrobials reduced the ASO value
      and led to remission of the disease. After 1 month of antimicrobial treatment,
      the erythematous papules disappeared. The human leukocyte antigen (HLA) typing of
      the father was HLA-A24, A31, B7, B39, and Cw7, and that of the daughter was HLA
      A24, A31, B39, and Cw7. Both possessed HLA-A24, B39, and Cw7. The HLA typing of
      other family members was also studied. The mother had HLA-A11, A24, B39, B62,
      Cw4, and Cw7, and her son had HLA-A11, A24, B7, B62, Cw4, and Cw7. The result of
      HLA typing is shown in Table 1. Lymphocyte stimulating test was performed using
      heat-killed S. pyogenes which were boiled at 70 degrees C for 10 min and
      sonicated. The stimulation index was twofold higher in the daughter than in the
      father (Fig. 3).

PMID- 11454090
TI  - Mongolian spots with involvement of the temporal area.
AB  - A Chinese baby girl was born after an uncomplicated pregnancy and a normal
      spontaneous vaginal delivery to a gravida 2, para 1, 32-year-old mother at 37
      weeks' gestation. Neither parent had a history of alcohol or drug ingestion.
      There was no history of consanguinity. The Apgar scores were 7 at 1 min and 9 at
      5 min. Her birth weight was 5 lb 14 oz and her length was 46 cm. At birth, she
      was noted to have grayish areas on the face and lower back. The infant was seen
      at 3 months of age because of persistent regurgitations. On average, she
      regurgitated 7-8 times a day. Physical examination showed that the infant was not
      in distress. Her weight was 6 lb 4 oz and length 47 cm. She had a Mongolian spot
      measuring 0.8 x 1.2 cm in the left temporal area (Fig. 1) and another Mongolian
      spot measuring 4 cm in diameter in the lumbar area. The Mongolian spots were
      grayish in color and the pigmentation was uniform in intensity. The rest of the
      examination was essentially normal. The infant was diagnosed to have Mongolian
      spots and gastroesophageal reflux. The latter was treated with postural therapy,
      thickened feedings, and metoclopramide 0.35 mg q.i.d. The infant was seen again
      at 4 months of age for a reassessment. There was no noticeable change in shape,
      size, or color of the Mongolian spots.

PMID- 11454091
TI  - Familial koilonychia.
AB  - A 2-year-old boy with flat and spoon-shaped nail plates was referred to us. His
      mother had noticed that his fingernails were quite soft when he was born. After 2
      months, the nails became flat or spoon-shaped; the toenail plates also became
      rough and flat. Systemic examination revealed nothing unusual. All his fingernail
      plates were quite thin, and had concave surfaces; the distal edges of some nail
      plates were rough and darkened (Fig. 1). His great, second and middle toenails on
      both sides showed the same abnormalities as the fingernails. Routine laboratory
      tests were normal; serum levels of iron, zinc, calcium, and magnesium were within
      normal limits. Repeated microscopic examination and culture of fungi from both
      fingernails and toenails were negative. Histologic examination of the distal
      edges of some of his fingernail plates was basically normal. When checking
      members of the family, we noticed that the boy's mother and maternal grandmother
      had similar nail problems (out of 14 members of three generations), although no
      systemic or other skin disorders were noticed. All the fingernails of the boy's
      mother were lusterless and concave with darkening of the distal edges (Fig. 2).
      All her toenails were rough, lusterless, and brown; some of them had longitudinal
      ridges. His maternal grandmother had light brown colored fingernail plates with
      concave profiles (Fig. 3), and dark brown or even blackish colored toenails. Both
      the mother and maternal grandmother acknowledged that their nails were abnormal
      from early childhood. Repeated microscopic examination and culture of fungi from
      both fingernails and toenails were negative. Several distal portions of the nail
      plates were collected for histologic examination. The fingernail plates of the
      boy's mother showed numerous parakeratotic cells in the middle zone, and those of
      his maternal grandmother showed diffuse parakeratotic cells; melanin granules
      were not found in those nail plates that were checked. Taken together, a
      diagnosis of familial koilonychia was established.

PMID- 11454092
TI  - Levamisole: a safe and economical weapon against pediculosis.
AB  - Twenty-eight patients with pediculosis capitis, defined as the presence of
      pruritus, living eggs, and/or lice in the hair, were enrolled in an uncontrolled
      open pilot study. The subjects were school-age girls (7-12 years old), apparently
      free of other diseases, and not treated for pediculosis for 4 weeks prior to this
      study. Family contacts were not treated for pediculosis. The mothers of the
      patients, who had given informed consent, were asked not to use any topical
      pediculocide on the girls during the drug trial. Other than the drug administered
      in the study, the subjects did not take any oral medicine, including
      cotrimoxazole and ivermectin, during the trial. Treatment consisted of 3.5 mg/kg
      once daily oral administration of levamisole for 10 successive days, which was
      given to the subjects in their school by health personnel. A 10-day course was
      chosen because the subjects lived in unhygienic and overcrowded conditions in a
      poor village where head lice infestation was hyperendemic. Therefore, two
      treatment courses spaced 10 days apart could not preclude new infestations from
      other affected persons and fomites and might have led to a false deduction of
      drug ineffectiveness. Substituting "N" for the grade of living nits and "L" for
      adult lice, three forms of response based on the meticulous examination of the
      entire scalp with the use of a lens with high magnification and a powerful light
      source were considered: (i) total responsiveness, defined as N2 = 0 and L2 = 0;
      (ii) partial responsiveness, defined as 0 not equal N2 < N1 and 0 not equal L2 <
      L1; and (iii) complete unresponsiveness, defined as N2 > or = N1 or L2 > or = L1.
      The detection of unhatched nits which were operculated and generally located
      within one-quarter of an inch of the scalp was used to indicate the presence of
      lice infestation and also to judge the clinical response. For those small nits
      whose opercula were difficult to see with a hand lens, a low power microscopic
      study was performed to determine whether the nits were unhatched or not. Of the
      28 girls enrolled in the study, one patient refused to take the drug after 2 days
      of treatment. No adverse reactions were noted in any of the 28 subjects. On the
      11th day, meticulous hair examination showed that 23 patients had responded to
      treatment (85%; 95% confidence interval (CI): 66-94%). Of these, 18 showed
      complete responsiveness (67%; 95% CI: 48-82%). More complete information is given
      in Table 1. Confidence intervals were calculated using the likelihood method.
      This study suggests that levamisole is effective against pediculosis with a dose
      of 3.5 mg/kg administered for 10 days.

PMID- 11454093
TI  - Cutaneous T-cell lymphoma treated with electron beam irradiation in Indian
      patients.
AB  - BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a rare occurrence in India. Total
      skin electron irradiation (TSEI) is a well-accepted therapeutic modality for the
      treatment of CTCL throughout the world. The aim of this study was to
      retrospectively analyze the treatment outcome of TSEI in Indian patients with
      CTCL and to determine the different parameters affecting the disease-free
      survival in these patients. METHODS: Fourteen male patients between 27 and 82
      years of age with CTCL (duration of disease, 4 months to 2 years) were treated
      with TSEI between 1985 and 1998. Seven patients had early stage disease, while
      the other seven had advanced disease. Two patients had lymph node involvement at
      the time of presentation. The TSEI was performed according to the Stanford
      technique delivering a total dose in the range 8-36 Gy. RESULTS: Of the 14
      patients, 10 showed complete remission following TSEI. The total follow-up period
      was 4-110 months (median, 52 months). Five patients were disease free at the end
      of 5 years. Two patients died due to rapid progression of the disease, while the
      cutaneous lesions relapsed in three patients after 2-27 months and one patient
      developed visceral metastasis. CONCLUSIONS: TSEI was an effective therapeutic
      modality for the treatment of CTCL in this group of patients, both as a curative
      and palliative measure, although the long-term prognosis is poor.

PMID- 11454094
TI  - Livedo reticularis associated with renal cell carcinoma.

PMID- 11454095
TI  - Angiolymphoid hyperplasia with eosinophilia in the shoulder.

PMID- 11454096
TI  - Some useful clinical clues and techniques in the diagnosis of tuberculoid
      leprosy.

PMID- 11454097
TI  - No association between human herpesvirus 8 and arsenical skin cancers.

PMID- 11454099
TI  - Viruses and apoptosis.
AB  - Apoptosis, or programmed cell death, is essential in development and homeostasis
      in multi-cellular organisms. It is also an important component of the cellular
      response to injury. Many cells undergo apoptosis in response to viral infection,
      with a consequent reduction in the release of progeny virus. Viruses have
      therefore evolved multiple distinct mechanisms for modulating host cell
      apoptosis. Viruses may interfere with either the highly conserved 'effector'
      mechanisms of programmed cell death or regulatory mechanisms specific to
      mammalian cells. In addition to conferring a selective advantage to the virus,
      the capacity to prevent apoptosis has an essential role in the transformation of
      the host cell by oncogenic viruses. This article provides a focussed review of
      apoptosis and illustrates how the study of viruses has informed our understanding
      of this process. Selected mechanisms by which viral gene products interfere with
      cell death are discussed in detail and used to illustrate the general principles
      of the interactions between viruses and apoptosis.

PMID- 11454101
TI  - Idiopathic pneumonia syndrome after bone marrow transplantation: the role of pre
      transplant radiation conditioning and local cytokine dysregulation in promoting
      lung inflammation and fibrosis.
AB  - Pulmonary complications and graft-vs.-host disease (GVHD) remain severe threats
      to survival after bone marrow transplantation (BMT). Idiopathic pneumonia
      syndrome (IPS) accounts for nearly 50% of all the cases of interstitial
      pneumonitis after BMT. IPS is characterized by an early inflammatory phase
      followed by chronic inflammation and fibrosis of lung tissue; however, the
      immunopathogenesis of this disease is not yet clearly understood. This biphasic
      syndrome has been reported to be associated with pre-transplant radiation
      conditioning in some studies while others have suggested that GVHD or autoimmune
      phenomena may be responsible for its development. The early post-BMT phase is
      characterized by the presence of inflammatory cytokines whose net effect is to
      promote lymphocyte influx into lungs with minimal fibrosis, that leads to an
      acute form of graft-vs.-host reaction-mediated pulmonary tissue damage. Gradual
      changes over time in leucocyte influx and activation lead to dysregulated wound
      repair mechanisms resulting from the shift in the balance of cytokines that
      promote fibrosis. Using data from new animal models of IPS and information from
      studies of human IPS, we hypothesize that cytokine-modulated immunological
      mechanisms which occur during the acute and chronic phases after bone marrow
      transplantation lead to the development of the progressive, inflammatory, and
      fibrotic lung disease typical of idiopathic pneumonia syndrome.

PMID- 11454102
TI  - The effect of enalapril and verapamil on the left ventricular hypertrophy and the
      left ventricular cardiomyocyte numerical density in rats submitted to nitric
      oxide inhibition.
AB  - Forty male Wistar rats were separated into four groups of ten rats each (control
      and other three groups that have received nitric oxide (NO) synthesis inhibitor L
      NAME) but the last two groups have concomitantly received antihypertensive drugs
      (Enalapril and Verapamil). After 40 days of experimentation, the heart and the
      ventricles were measured. The optical disector was used for the calculation of
      numerical density of the cardiomyocytes (Nv[c]). The left ventricular myocytes
      number (N[c]) was calculated as the product of Nv[c] and the left ventricular
      myocardium volume (LVMV) that was determined by using the Scherle's method. In
      the L-NAME group the blood pressure (BP) had a significant weekly increment. In
      the enalapril and the verapamil groups, BP increased in the first two weeks, but
      decreased in the following weeks. The LVMV increased in the L-NAME rats and
      decreased in the enalapril and verapamil animals. The Nv[c] and N[c] decreased in
      the L-NAME rats but the verapamil and enalapril treatments maintained the Nv[c]
      close to the control group. In conclusion, the left ventricular hypertrophy and
      the significant decrease of the left ventricular cardiomyocyte number caused by
      the NO synthesis inhibition are efficiently prevented with the use of enalapril
      and verapamil.

PMID- 11454103
TI  - Morphological aspects of rabbit masseter muscle after cervical sympathectomy.
AB  - The objective of this paper was to study the effect of sympathetic innervation on
      morphological and histochemical aspects of skeletal muscle tissue. Rabbit
      masseter muscle was studied using histochemical and immunohistochemical methods
      for periods of up to 18 months post-sympathectomy. The morphological and
      enzymatic characteristics of control masseter muscles were similar on both the
      left and right sides. The main features were muscle fibres with a mosaic pattern
      and a predominance of type IIa fibres, followed by type I. Type IIb fibres showed
      very low frequency. Sympathectomized animals showed varying degrees of metabolic
      and morphological alterations, especially 18 months after sympathectomy. The
      first five groups showed a higher frequency of type I fibres, whilst the oldest
      group showed a higher frequency of type IIb fibres. In the oldest group, a
      significant variation in fibre diameter was observed. Many fibres showed small
      diameter, atrophy, hypertrophy, splitting, and necrosis. Areas with fibrosis were
      observed. Thus cervical sympathectomy induced morphological alterations in the
      masseter muscles. These alterations were, in part, similar to both denervation
      and myopathy. These findings indicate that sympathetic innervation contributes to
      the maintenance of the morphological and metabolic features of masseter muscle
      fibres.

PMID- 11454100
TI  - Hepatitis B virus and hepatocellular carcinoma.
AB  - Chronic hepatitis B virus (HBV) infection is a major global cause of
      hepatocellular carcinoma (HCC). Individuals who are chronic carriers have a
      greater than 100-fold increased relative risk of developing the tumour. Several
      mechanisms of HBV-induced HCC have been proposed. Integration of HBV DNA into the
      genome of hepatocytes occurs commonly, although integration at cellular sites
      that are important for regulation of hepatocyte proliferation appears to be a
      rare event. Functions of the HBx protein are also potentially oncogenic. These
      include transcriptional activation of cellular growth regulatory genes,
      modulation of apoptosis and inhibition of nucleotide excision repair of damaged
      cellular DNA. The effects of HBx are mediated by interaction with cellular
      proteins and activation of cell signalling pathways. Variations in HBV genome
      sequences may be important in hepatocarcinogenesis, although their significance
      has not yet been completely elucidated. Necroinflammatory hepatic disease, which
      often accompanies chronic HBV infection, may contribute indirectly to hepatocyte
      transformation in a number of ways, including by facilitating HBV DNA
      integration, predisposing to the acquisition of cellular mutations and generating
      mutagenic oxygen reactive species. Although HCC is a malignancy with a poor
      prognosis, the availability of an effective vaccine against HBV infection, and
      its inclusion in the Expanded Programme of Immunization of many countries, augurs
      well for the eventual elimination of HBV-associated HCC.

PMID- 11454104
TI  - Intralesional isotype profiles in human localized cutaneous leishmaniasis
      lesions.
AB  - This immunocytochemical study evaluates the presence of IgG1-4, IgA and IgE
      immunoglobulins in active lesions of 25 localized cutaneous leishmaniasis
      patients from three bioclimatic areas (Awa, Afa and Bsha) in Merida State,
      Venezuela. All immunoglobulin isotypes except IgE were detected, with variable
      intensity, in one or more of the epidermal or dermal components of skin lesions.
      IgG1 and IgG2 were detected significantly more frequently than IgG3, IgG4 and
      IgA. The ranking of the isotypes according to frequency of detection was the same
      in all areas: IgG1 = IgG2 > IgG3 = IgG4 = IgA, but considered as whole, all
      isotypes were detected significantly more frequently in patients from the Awa
      area than in those from the Bsha area. The predominant expression of isotypes
      IgG1 and IgG2 suggests a preferential Th1 like immune response. Anti-Leishmania
      immunoserum stained only parasites and their debris, suggesting that most of the
      immunostaining was nonspecific.

PMID- 11454106
TI  - Tolterodine: a safe and effective treatment for older patients with overactive
      bladder.
AB  - OBJECTIVE: To investigate the clinical safety and efficacy of two dosages of
      tolterodine in older patients with symptoms attributable to overactive bladder.
      DESIGN: Randomized, double-blind, placebo-controlled, parallel-group,
      multinational, phase III study. SETTING: Incontinence, older care, urological,
      and urogynecological clinics in the United Kingdom, France, and the Republic of
      Ireland. PARTICIPANTS: One hundred and seventy-seven older patients (age > or =65
      years) with symptoms of urinary urgency, increased frequency of micturition (> or
      =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours).
      INTERVENTION: Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4
      weeks. MEASUREMENTS: Safety and tolerability were evaluated through spontaneously
      reported adverse events, electrocardiogram, and blood pressure measurements.
      Efficacy was assessed using micturition diary variables: mean change from
      baseline in frequency of micturition and number of incontinence episodes/24
      hours. RESULTS: The mean age of the patient population was 75 years. Overall, >
      or =87% of patients completed the study. Neither dosage of tolterodine was
      associated with serious drug-related adverse events during the study. No cardiac
      arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the
      most common adverse event in both the placebo and tolterodine treatment groups.
      Three percent of patients in the tolterodine 2 mg bid group discontinued
      treatment because of dry mouth, compared with 2% of placebo-treated patients.
      Compared with placebo, statistically significant decreases in micturition
      frequency were apparent in both tolterodine treatment groups. Furthermore,
      patients treated with tolterodine 2 mg bid had statistically significant
      decreases in urge incontinence episodes/24 hours and increases in volume voided
      per micturition compared with placebo. CONCLUSION: Tolterodine (taken for 4
      weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the
      treatment of older patients with urinary symptoms attributable to overactive
      bladder.

PMID- 11454107
TI  - Prompted voiding for nighttime incontinence in nursing homes: is it effective?
AB  - OBJECTIVES: To determine whether prompted voiding (PV) is effective for nighttime
      urinary incontinence in nursing home (NH) residents and whether residents who
      respond well to daytime PV also respond well at night. DESIGN: Prospective case
      series. SETTING: Four community NHs. PARTICIPANTS: Sixty-one long-stay
      incontinent NH residents of mean age 88 years, 75% female. MEASUREMENTS: The
      percentage of hourly checks for wetness and the appropriate toileting rate
      (continent voids divided by total voids) were measured during 3 days (7 a.m.-7
      p.m.) of PV, and for an average of 5 nights (7 p.m.-7 a.m.), during which a
      modified PV protocol, designed to be minimally disruptive to sleep, was carried
      out. RESULTS: Fourteen residents (23%) responded well to daytime PV, with average
      wetness and appropriate toileting rates of 5% and 73%, respectively. In the group
      as a whole, nighttime PV was not effective, with wetness and appropriate
      toileting rates of 49% and 18%, respectively. Among those who responded well to
      daytime PV, wetness rates during nighttime PV remained significantly higher than
      during the day (24% vs. 5%; P = .000), and nighttime appropriate toileting rates
      were significantly lower (39% vs. 73%; P = .002). The poor response rate at night
      was primarily observed between 10 p.m. and 6 a.m. CONCLUSIONS: In this sample of
      incontinent NH residents, nighttime PV, even when carried out so as to minimize
      sleep disruption, was not an effective intervention. Although residents who
      responded well to daytime PV responded better to nighttime PV than those who did
      not respond to daytime PV, their wetness rates remained relatively high and their
      appropriate toileting rates were low. These data suggest that routine nighttime
      toileting programs should not be carried out for the majority of incontinent NH
      residents. Instead, individualized care based on resident's preferences,
      willingness to toilet at night, and sleep patterns should be emphasized.

PMID- 11454108
TI  - Urinary incontinence treatment preferences in long-term care.
AB  - OBJECTIVE: To elicit preferences for different urinary incontinence (UI)
      treatments in long-term care (LTC) from groups likely to serve as proxy decision
      makers for LTC residents. DESIGN: A descriptive, comparative study of preference
      for UI treatments of frail older adults, family members of nursing home (NH)
      residents, and LTC nursing staff. Surveys were mailed to families and self
      administered by staff. Older adults were interviewed. SETTING: Four LTC
      facilities and two residential-care facilities in Los Angeles. PARTICIPANTS: Four
      hundred and three family members of incontinent NH residents were mailed surveys.
      Sixty-six nursing staff caring for these incontinent residents and 79 older adult
      residents of care facilities (nine cognitively intact NH respondents and 70
      residential care residents) answered surveys. MEASUREMENTS: Preference rankings
      between seven paired combinations of five different UI treatments were measured
      on an 11-point visual analog scale, with the verbal anchors "definitely prefer"
      this treatment, "probably prefer" this treatment, and "uncertain." Respondents
      gave open-ended comments as well. RESULTS: Forty-two percent of family members
      (171/ 403) returned the mailed survey. Of all respondents, 85% "definitely" or
      "probably" preferred diapers, and 77% "definitely" or "probably" preferred
      prompted voiding (PV) to indwelling catheterization. Respondent groups
      occasionally differed significantly in their preferences. In choosing between
      treatment pairs using a visual analogue scale, nurses preferred PV to diapers
      significantly more than did older adults or families (both of whom preferred
      diapers) (F (2,295) = 13.11, P < .0001). Older adults, compared with family and
      nurse respondents, showed a significantly stronger preference for medications
      over diapers (F (2,296) = 41.54, P < .0001). In open-ended responses, older
      adults stated that they would choose a UI treatment based in part upon criteria
      of feeling dry, being natural, not causing embarrassment, being easy, and not
      resulting in dependence. Nurses said that they would base their choice of UI
      treatment upon increasing self-esteem and avoiding infection. CONCLUSIONS:
      Although there was wide variation within and between groups about preferred UI
      treatment, most respondents preferred noninvasive strategies (diapers and PV) to
      invasive strategies (indwelling catheters and electrical stimulation). Older
      adults preferred to a greater degree medications and electrical stimulation,
      therapies directed at the underlying cause of UI. Despite data documenting that
      diapering is a less time intensive way to manage UI and that toileting programs
      are difficult to maintain in LTC, nurses viewed PV as "natural" and strongly
      preferred it to diapering. Several family members and older adults viewed PV as
      "embarrassing" and "fostering dependence." These data highlight the need to
      elicit preferences for UI treatment among LTC residents and their families.

PMID- 11454109
TI  - Possible medication errors in home healthcare patients.
AB  - OBJECTIVE: To determine the frequency of possible medication errors in a
      population of older home healthcare patients according to expert panel objective
      criteria. DESIGN: A cross-sectional survey. SETTING: Two of the largest urban
      home healthcare agencies in the United States. PARTICIPANTS: Home healthcare
      patients age 65 and older admitted to selected offices of these agencies between
      October 1996 and September 1998. MEASUREMENTS: We used two sets of consensus
      based expert panel criteria to define possible medication errors. The Home Health
      Criteria identify patients with patterns of medication use and signs and symptoms
      that indicate sufficient likelihood of a medication-related problem to warrant
      reevaluating the patient. The Beers criteria identify medications that experts
      have deemed generally inappropriate for older patients. RESULTS: The 6,718 study
      subjects took a median of five drugs; 19% were taking nine or more medications. A
      possible medication error was identified for 19% of patients according to Home
      Health Criteria, 17% according to the Beers criteria, and 30% according to
      either. Possible errors increased linearly with number of medications taken. When
      patients taking one to three medications were compared with those taking nine or
      more drugs, the percentages with possible errors were, respectively, 10% and 32%
      for the Home Health Criteria, 8% and 32% for the Beers criteria, and 16% and 50%
      for both. CONCLUSION: Nearly one-third of the home healthcare patients surveyed
      had evidence of a potential medication problem or were taking a drug considered
      inappropriate for older people. More-effective methods are needed to improve
      medication use in this vulnerable population.

PMID- 11454110
TI  - The relationship of psychosocial factors to total mortality among older Japanese
      American men: the Honolulu Heart Program.
AB  - OBJECTIVE: To examine the predictive value of psychosocial factors as risk
      factors for all-cause mortality. DESIGN: A community-based longitudinal cohort
      study: The Honolulu Heart Program. SETTING: Population-based study conducted in
      Oahu, Hawaii. PARTICIPANTS: Three thousand four hundred and ninety-seven men age
      71 to 93 were examined and followed prospectively for all-cause mortality for an
      average of 6 years. MEASUREMENTS: Psychosocial data were obtained using the
      Lubben Social Networks Scale (LSNS). The LSNS consists of 10 items-family
      relationships (three items), relationships with friends (three items), and
      interdependent social supports and living arrangements (four items). We divided
      the LSNS score into quartiles for comparison, with the first quartile
      representing the lowest social support and the fourth quartile representing the
      highest social support. RESULTS: A significant dose-response relationship was
      noted with LSNS score and total mortality: 33.8% in the first quartile died over
      the follow-up period, 23.4% in the second, 18% in the third, and 15.7% in the
      fourth (P < .001). Six-year age-adjusted mortality rates were 66.2, 45.7, 37.8,
      and 33.7 per 1,000 person years in the first, second, third, and fourth,
      respectively (P < .001). Using age-adjusted Cox proportional hazards models, with
      the first quartile of LSNS as the reference group, relative risk for mortality
      was 0.69 (95% confidence interval (CI) = 0.58-0.82), 0.57 (95% CI = 0.47-0.70),
      and 0.52 (95% CI = 0.43-0.64) in the second, third, and fourth quartiles,
      respectively. Cox models were repeated, controlling for age and smoking status,
      and low LSNS scores remained significantly associated with higher mortality (P =
      .0001). CONCLUSIONS: Our findings suggest that social networks were significantly
      independently associated with 6-year all-cause mortality in this cohort of older
      Japanese-American men. Social interventions in old age may reduce early
      mortality.

PMID- 11454111
TI  - The association of bone mineral density and depression in an older population.
AB  - OBJECTIVE: To evaluate the association between bone mineral density (BMD) and
      measurements of depression in an older population. DESIGN: Population-based,
      cross-sectional study. SETTING: Study subjects were participants in the
      Cardiovascular Health Study (CHS), a longitudinal, long-term, follow-up study, at
      the University of California Davis (Sacramento, California) and the University of
      Pittsburgh (Pittsburgh, Pennsylvania) clinical centers. PARTICIPANTS: A random
      sample of 1,566 Medicare enrollees age 65 and older enrolled in the CHS.
      MEASUREMENTS: Total hip BMD, measured using dual energy x-ray absorptiometry
      (DEXA), after adjustment for multiple covariates, was compared with depression
      evaluated with the Center for Epidemiological Studies 10-item Depression Scale
      (CES-Dm). Risk factors for osteoporosis were compared in depressed and
      nondepressed participants. Potential correlates were entered into a regression
      model. Depression scores were compared in normal, osteopenic, and osteoporotic
      individuals. RESULTS: Sixteen percent of participants were clinically depressed;
      9% had BMDs in the osteoporotic range. Mean BMD was 40 mg/cm2 lower in those with
      clinical depression. High CES-Dm scores were associated with lower BMD (P < .001)
      when adjusted for body mass index (BMI), age, kilocalories of activity, estrogen
      use, gender, race, smoking and drinking. When stratified by race, this remained
      true for all Caucasians (P < .01), all African Americans (P < .05), and when
      stratified by race and gender the association remained only for all Caucasian
      women (P < .001). In women and Caucasian men there was an increase in depression
      scores among individuals with osteoporotic-range BMDs. CONCLUSIONS: A significant
      association was found between BMD and depressive symptoms after adjustment for
      osteoporosis risk factors. In Caucasians, depressive symptoms were associated
      with both osteoporotic and osteopenic levels of BMD. Causality cannot be
      ascribed, with only one measurement of BMD. We postulate that there may be an
      unmeasured third factor, such as an endogenous steroid, that is responsible for
      both low BMD and depression.

PMID- 11454112
TI  - Longitudinal changes in body mass index and body composition over 3 years and
      relationship to health outcomes in Hong Kong Chinese age 70 and older.
AB  - OBJECTIVES: To determine longitudinal changes in body mass index (BMI) and body
      composition with age and the relationship between these changes with mortality,
      morbidity, functional capacity, and other health outcome measures. DESIGN: A 3
      year longitudinal study of a random sample of community-living subjects. SETTING:
      Older Chinese in the Hong Kong Special Administrative Region of China.
      PARTICIPANTS: Two thousand and thirty-two Chinese subjects age 70 and older
      recruited territory-wide by proportional random sampling. MEASUREMENTS: Baseline
      information collected included medical history, self-perceived health, Barthel
      Index, Geriatric Depression Score, time taken to complete a 16-foot walk, height,
      weight, mid-arm circumference, arm skin-fold thickness, and waist/hip ratio. Body
      composition was calculated from prediction equation. Outcome measures included
      mortality, development of new diseases, Barthel Index, time taken for 16-foot
      walk, self-perceived health, and Geriatric Depression Score. RESULTS: All
      parameters, with the exception of triceps skin-fold thickness in men, decreased,
      regardless of presence or absence of disease. The decrease in arm circumference,
      triceps skin-fold thickness, and total body fat (TBF) was greater in women than
      in men, whereas men had a greater decrease in fat-free mass (FFM). Even in the
      absence of disease, three times as many subjects lost > or =5kg in weight as
      gained > or =5kg (15% vs. 5%), and only age could be identified as a contributing
      factor to this weight loss. In the absence of disease, lower anthropometric
      indices were associated with greater mortality, development of new disease (in
      women only), dependency, and poor performance measure. Waist-hip ratio was not
      associated with mortality or any other health outcomes. Decrease in both FFM and
      TBF were associated with worse outcomes, the effect being more marked in women.
      CONCLUSION: In the older population, changes in weight and body composition occur
      even in the absence of disease and are associated with mortality and physical
      functioning level. Weight loss rather than weight gain appears to be more
      important in this population, and promotion of life-style interventions targeted
      at weight maintenance would be important.

PMID- 11454113
TI  - Gait alterations associated with walking impairment in people with peripheral
      arterial disease with and without intermittent claudication.
AB  - OBJECTIVES: To describe gait alterations associated with impaired walking
      endurance in patients with and without lower-extremity peripheral arterial
      disease (PAD) and determine whether the Caltrac accelerometer provides a valid
      measure of physical activity in PAD. DESIGN: Cross-sectional. SETTING: Academic
      medical center. PARTICIPANTS: PAD (n = 40) and non-PAD patients (n = 22) from two
      Chicago hospitals. MEASUREMENTS: Participants underwent measurement of the ankle
      brachial index (ABI), leg length, and 6-minute walk. Steps per minute and step
      length were measured during the first and last 100 feet of the 6-minute walk.
      Participants wore a Caltrac accelerometer, sensitive to vertical acceleration,
      during the 6-minute walk and for 7 continuous days. RESULTS: Five PAD
      participants (13%) and one non-PAD participant (5%) ceased walking before the end
      of 6 minutes. Among the remaining participants, distance walked in 6 minutes was
      more highly related to walking velocity during the last 100 feet of the walk than
      walking velocity during the first 100 feet. ABI was associated significantly with
      cadence (20.77 steps/minute per unit ABI, P <.001) but not step length (10.12
      centimeters/unit ABI, P =.08). ABI was associated significantly with 6-minute
      walk distance (493 feet/unit ABI, P =.018), but this association disappeared
      completely after adjustment for step length and cadence. We found no difference
      in accelerometer scores between PAD and non-PAD participants over a fixed
      distance of 800 feet (7.34 vs 7.17 activity units, P =.789). However, scores were
      significantly different after 7 days (730.8 vs 1,485.0 activity units, P =.003).
      CONCLUSION: Walking performance in PAD patients who completed 6 minutes of
      walking was largely determined by a decline in walking velocity rather than
      slower initial walking velocity. ABI was more closely associated with cadence
      than step length. Future studies should assess the effect of exercise programs
      and revascularization on cadence and step length in PAD.

PMID- 11454114
TI  - Exercise rehabilitation improves functional outcomes and peripheral circulation
      in patients with intermittent claudication: a randomized controlled trial.
AB  - OBJECTIVE: To determine the effects of a 6-month exercise program on ambulatory
      function, free-living daily physical activity, peripheral circulation, and health
      related quality of life (QOL) in disabled older patients with intermittent
      claudication. DESIGN: Prospective, randomized controlled trial. SETTING:
      University Medical (Center and Veterans Affairs Medical Center, Baltimore,
      Maryland. PARTICIPANTS: Thirty-one of 61 patients with Fontaine stage II
      peripheral arterial occlusive disease (PAOD) were randomized to exercise
      rehabilitation and 30 to usual-care control. Three patients from the exercise
      group and six patients from the control group dropped out, leaving 28 and 24
      patients, respectively, completing the study in each group. INTERVENTION: Six
      months of exercise rehabilitation. MEASUREMENTS: Treadmill distance walked to
      onset of claudication and to maximal claudication, ambulatory function,
      peripheral circulation, perceived QOL, and daily physical activity. RESULTS:
      Compliance with the exercise program was 73% of the possible sessions. Exercise
      rehabilitation increased treadmill distance walked to onset of claudication by
      134% (P < .001) and to maximal claudication by 77% (P < .001), walking economy by
      12% (P = .003), 6-minute walk distance by 12% (P < .001), and maximal calf blood
      flow by 30% (P < .001). Changes in distance walked to maximal pain correlated
      with changes in walking economy (r = -.50, P = .013) and changes in maximal calf
      blood flow (r = .38, P = .047). Exercise rehabilitation increased accelerometer
      derived daily physical activity by 38% (P < .001); this change correlated with
      the change in distance walked to maximal pain (r = .45, P = .020). These
      improvements were significantly better than the changes in the control group (P <
      .05). CONCLUSION: Improvements in claudication following exercise rehabilitation
      in older PAOD patients are dependent on improvements in peripheral circulation
      and walking economy. Improvement in treadmill claudication distances in these
      patients translated into increased accelerometer-derived physical activity in the
      community, which enabled the patients to become more functionally independent.

PMID- 11454115
TI  - Trends and outcomes in the hospitalization of older Americans for cardiac
      conduction disorders or arrhythmias, 1991-1998.
AB  - OBJECTIVE: To identify epidemiological trends and measure outcomes in elderly
      patients hospitalized for cardiac conduction disorders or arrhythmias. DESIGN:
      Review of the standard 5% samples of the Medicare Provider Analysis and Review
      Files to characterize 144,512 discharges from 1991 through 1998 in which the
      principal diagnosis was a conduction disorder or arrhythmia, using the
      corresponding Enrollment Databases for denominator data. SETTING: Short-stay
      hospitals in the United States. PARTICIPANTS: Medicare beneficiaries age 65 and
      older in the standard 5% sample. MEASUREMENTS: Diagnosis-specific trends and
      rates; discharges by year; cumulative age-, race-, and sex-specific discharge
      rates; mean length of stay in hospital and in intensive care; mean Medicare
      reimbursement to the hospital; case-fatality rate in hospital; discharge
      destinations of patients discharged alive. RESULTS: Annual hospitalizations for
      sinoatrial node dysfunction, atrial flutter, atrial fibrillation, or ventricular
      fibrillation increased more rapidly than did the elderly Medicare beneficiary
      population. Hospitalizations with a principal diagnosis of ventricular
      extrasystoles or asystole showed steep secular declines. Discharge rates for
      sinoatrial node dysfunction, a group of rhythms with a nonsinus pacemaker, atrial
      fibrillation, Mobitz I, or complete atrioventricular block all increased steeply
      and continuously with patient age. In contrast, discharge rates for atrial
      flutter or ventricular tachycardia or fibrillation peaked among 75- to 84-year
      old patients. White men were at uniquely high risk of hospitalization for atrial
      flutter or ventricular tachycardia or fibrillation, and, among the white
      majority, men had higher discharge rates than women for nine of the 11 commonest
      rubrics. Whites, particularly white women, had the highest discharge rates for
      atrial fibrillation. Blacks, especially black women, were at disproportionate
      risk for hospitalization for the group of nonsinus pacemaker rhythms. Diagnosis
      specific mean resource costs were strongly correlated with each other and with
      mean Medicare reimbursement but not with case-fatality rate. CONCLUSION: Medicare
      claims data demonstrated striking differences among and within diagnoses of heart
      blocks or arrhythmias in terms of the populations at greatest risk for
      hospitalization. This variation should be explored further to generate and test
      hypotheses about differential causation or delivery of care.

PMID- 11454116
TI  - Factors associated with home versus institutional death among cancer patients in
      Connecticut.
AB  - OBJECTIVE: To assess the relationships between home death and a set of
      demographic, disease-related, and health-resource factors among individuals who
      died of cancer. DESIGN: Prospective cohort study. SETTING: All adult deaths from
      cancer in Connecticut during 1994. PARTICIPANTS: Six thousand eight hundred and
      thirteen individuals who met all of the following criteria: died of a cancer
      related cause in 1994, had previously been diagnosed with cancer in Connecticut,
      and were age 18 and older at the time of death. MEASUREMENT: Site of death.
      RESULTS: Twenty-nine percent of the study sample died at home, 42% died in a
      hospital, 17% died in a nursing home, and 11% died in an inpatient hospice
      facility. Multivariate analysis indicated that demographic characteristics (being
      married, female, white, and residing in a higher income area), disease-related
      factors (type of cancer, longer survival postdiagnosis), and health-resource
      factors (greater availability of hospice providers, less availability of hospital
      beds) were associated with dying at home rather than in a hospital or inpatient
      hospice. CONCLUSIONS: The implications of this study for clinical practice and
      health planning are considerable. The findings identify groups (men, unmarried
      individuals, and those living in lower income areas) at higher risk for
      institutionalized death-groups that may be targeted for possible interventions to
      promote home death when home death is preferred by patients and their families.
      Further, the findings suggest that site of death is influenced by available
      health-system resources. Thus, if home death is to be supported, the relative
      availability of hospital beds and hospice providers may be an effective policy
      tool for promoting home death.

PMID- 11454117
TI  - Death at home following a targeted advance-care planning process at home: the
      kitchen table discussion.
AB  - OBJECTIVE: To determine whether home health agency patients' preferences to die
      at home can be honored following a structured, professionally facilitated advance
      care planning (ACP) process provided in the home. DESIGN: A case series of
      patients who were identified by their home health agency nurses as having a life
      limiting illness and then referred for social service assessment, followed for at
      least 6 months, with median follow-up of 191 days. SETTING: A large, urban, home
      health agency owned by a not-for-profit integrated healthcare system.
      PARTICIPANTS: Eighty-four adult patients (median age 75, range 37-94) receiving
      home care services other than hospice. INTERVENTION: Formally structured social
      work visits at patients' homes to discuss end-of-life issues, with communication
      of results to home health nurses and attending physicians. Social workers
      performed standard psychosocial assessments, obtained patient and family
      preferences regarding end-of-life care, and provided education about hospice
      services. MEASUREMENTS: Acceptance of the ACP process, preferences for location
      of end-of-life care, location of care at the end of life, adequacy of timing of
      intervention as measured by length of life after ACP, and use of hospice
      services. RESULTS: Eighty-three of 84 participants (99%) were willing to complete
      an ACP process in the home setting. Of the 54 patients expressing a clear
      preference for location of end-of-life care, 46 (82%) wanted this care to be at
      home. Thirty-nine (46%) of the participants died within 90 days of ACP; 58 (69%)
      died by the end of the study. Forty-three (75%) of these deaths occurred at home
      or in a hospice residence. Fifty-one (61%) patients used home, residential, or
      nursing home-based hospice services during the study. CONCLUSION: In this series
      of seriously ill home health patients, most preferred to die at home and
      virtually all were willing to participate in a home-based ACP process.
      Facilitating ACP among such patients and their families was associated with end
      of-life care at home. Use of hospice services was common following ACP in this
      population.

PMID- 11454118
TI  - An introduction to geriatrics for first-year medical students.
AB  - OBJECTIVE: To prepare medical students to better serve their older patients while
      raising awareness of geriatrics as a career choice. DESIGN: To determine the
      impact of a new educational program, attitudinal assessments were administered to
      the group before and after participation in the program and to a comparison group
      of nonintervention students. SETTING: University of Texas Health Science Center,
      San Antonio. PARTICIPANTS: Two hundred and three first-year medical students.
      MEASUREMENTS: Student response on a scale of one to six regarding four
      constructs: attitudes and beliefs about providing medical care for older people,
      knowledge and beliefs about aging, interest in pursuing clinical geriatrics, and
      interest in pursuing aging research. RESULTS: Four factors were consistently
      formed in the analysis process: beliefs about physical decline; comfort with
      older people; beliefs about career opportunities; and interest in geriatric
      research. The intervention group made significant gains in two areas: comfort
      with older people and understanding of physical decline in aging. Two new factors
      emerged in post-test data. CONCLUSIONS: The impact of the program was mixed.
      Although awareness of geriatrics and comfort with older people was increased,
      there was little change in career aspirations. Students in the program increased
      their awareness of physical decline in old age, setting the stage for teaching
      them about the physician's role with regard to function, and learned that
      geriatrics is a low-status specialty.

PMID- 11454119
TI  - Chronic idiopathic hyponatremia in older people due to syndrome of inappropriate
      antidiuretic hormone secretion (SIADH) possibly related to aging.
AB  - OBJECTIVE: To determine the prevalence of syndrome of inappropriate antidiuretic
      hormone secretion (SIADH) among older hyponatremic patients in a subacute
      geriatric facility, to identify patients with no apparent cause for the SIADH
      (idiopathic SIADH), and to determine their clinical characteristics. DESIGN:
      Prospective analysis of a cohort of older patients over a period of 3 months.
      SETTING: Two wards in a geriatric rehabilitation hospital. PARTICIPANTS: Patients
      aged 65 and older. MEASUREMENTS: All patients with hyponatremia (serum sodium
      <135 mmols/l) were clinically examined and relevant investigations were performed
      to determine the etiology of hyponatremia. Patients were observed for symptoms of
      hyponatremia. Hyponatremia was classified into possible SIADH and non-SIADH
      types. Patients with SIADH type hyponatremia were screened for possible causes.
      Past medical histories were obtained from the general practitioners. RESULTS: Of
      the 172 patients studied, 43 (25%) had hyponatremia. It was symptomatic in only
      four patients. Twenty-two (51%) had SIADH etiology. In nine (mean age 84 +/- 4),
      no cause for the SIADH was evident (presumed idiopathic SIADH) and in seven,
      hyponatremia (128-135 mmols/l) was chronic (12 to 72 months). Further reduction
      in serum sodium, which was symptomatic, was noted in two of these patients with
      the onset of pneumonia. CONCLUSION: Most older hyponatremic patients in a
      rehabilitation setting seem to have SIADH etiology. This study confirms the
      presence of a group of older individuals with chronic idiopathic hyponatremia in
      whom the underlying mechanism may be SIADH related to aging. Hyponatremia is
      modest in these patients and has little clinical significance. However, they may
      be at increased risk of developing symptomatic hyponatremia with intercurrent
      illnesses.

PMID- 11454120
TI  - Utilization of essential medications by vulnerable older people after a drug
      benefit cap: importance of mental disorders, chronic pain, and practice setting.
AB  - OBJECTIVE: To identify specific characteristics of patients, physicians, and
      treatment settings associated with decreased receipt of essential medications in
      a chronically ill, older population following a Medicaid three-prescription
      monthly reimbursement limit (cap). DESIGN: Quasi-experiment with bivariate and
      multivariate regression. SETTING: Patients in the New Hampshire Medicaid program
      and their regular prescribing physicians. PARTICIPANTS: Three hundred and forty
      three chronically ill Medicaid enrollees with regular use of essential
      medications for heart disease, asthma/chronic obstructive pulmonary disease,
      diabetes mellitus, seizure, or coagulation disorders who received an average of
      three or more prescriptions per month during the baseline year. MEASUREMENTS:
      Postcap patient-level change in standard monthly dose of essential medications
      compared with the baseline period, presence of 11 comorbidities (defined by
      regular use of specific indicator drugs), practice setting, and location of
      regular prescribing physician. RESULTS: The mean percentage change in standard
      doses of essential medications following the cap was -34.4%. Larger changes were
      significantly associated with several baseline measures: greater numbers of
      precap medications, greater numbers of comorbidities, longer hospitalizations,
      and greater use of ambulatory services. The three comorbidities associated with
      the largest relative reduction in essential drug use were psychoses/bipolar
      disorders, anxiety/sleep problems, and chronic pain. Patients of physicians in
      group practices, clinics, or hospitals tended to have smaller dose reductions
      than those whose physicians were in solo or small-group practice. CONCLUSIONS:
      Patients most at risk of reduced access to essential medications because of a
      reimbursement cap include those with multiple chronic illnesses requiring drug
      therapy, especially illnesses with a mental health component. Physicians in
      clinics or large group practices may have maintained patient medication regimens
      more effectively.

PMID- 11454121
TI  - The validation of a mailed health survey for screening of dementia of the
      Alzheimer's type.
AB  - OBJECTIVE: To test the efficacy of a mailed health survey, which included the
      Clock Completion Test (CCT), to screen previously undiagnosed older adults for
      dementia of the Alzheimer's type (DAT) in a community-dwelling population, and to
      determine whether the addition of selected risk factors for Alzheimer's disease
      (AD) would enhance the screening instrument's operating characteristics. DESIGN:
      Comparison of the results of a self-administered screen for DAT with the
      diagnosis of DAT by clinician evaluation or telephone interviews. SETTING: A
      geriatric assessment clinic. PARTICIPANTS: Three hundred and five women age 65
      and older from St. Louis, Missouri. MEASUREMENTS: The sensitivity and specificity
      of the CCT and the CCT plus risk factors for AD were evaluated using two
      standards: The Short Blessed Test (SBT) and the physician diagnosis of probable
      AD using National Institute of Neurological and Communicative Disorders and
      Stroke-Alzheimer's Disease and Related Disorders Association criteria. RESULTS:
      Sensitivity and specificity for the CCT by SBT criteria were 63% and 79%,
      respectively. Using the physician's assessment as a criterion, the CCT had better
      sensitivity (67%) but poorer specificity (69%). Adding two or more risk factors
      for AD improved sensitivity and specificity to 71% and 89% and, in the physician
      assessment subgroup, to 75% and 87%, primarily by halving the false-positive
      rate. CONCLUSION: The combination of the simple, self-administered CCT and two or
      more AD risk factors is a more effective screening instrument for DAT and
      potentially preclinical DAT than the CCT alone. However, the instrument may be
      better suited for use in an office setting because of a poor response rate by
      subjects with dementia.

PMID- 11454122
TI  - Effects of oral estrogen and progestin on the lower urinary tract among female
      nursing home residents.
AB  - OBJECTIVE: To examine the effects of oral estrogen/progestin on incontinence and
      related lower urinary tract conditions among female nursing home (NH) residents.
      DESIGN: Randomized placebo-controlled trial. SETTING: Five NHs. PARTICIPANTS:
      Thirty-two incontinent female residents of average age 88. MEASUREMENTS: Subjects
      were randomized to receive either oral estrogen (0.625 mg) combined with
      progesterone (2.5 mg) or placebo, daily for 6 months. Measures of incontinence
      severity, the clinical appearance of the vagina, vaginal and urethral cytology,
      and urine and vaginal cultures were made at baseline, 3 months, and 6 months. In
      addition to active drug or placebo, all subjects received regular toileting
      assistance (prompted voiding) by trained research aides during 3-day data
      collection periods to compensate for mobility and cognitive impairments. RESULTS:
      At 3 and 6 months there were no significant differences between the groups in the
      severity of incontinence, the prevalence of bacteriuria, or the results of
      vaginal cultures. Several clinical findings associated with atrophic vaginitis
      improved more in the active than the placebo group and vaginal pH and vaginal and
      urethral cytology exhibited a partial estrogenic effect. CONCLUSIONS: Our results
      must be interpreted with caution because of the size and the select nature of our
      subject sample. Up to 6 months of oral estrogen had only a partial estrogenic
      effect on vaginal and urethral epithelium and no clinical effects in this patient
      population. We believe that future studies of estrogen for urinary incontinence
      in frail NH residents should utilize a topical preparation and consider targeting
      urinary tract infection as an additional outcome measure.

PMID- 11454123
TI  - The role of benzodiazepines in the treatment of insomnia: meta-analysis of
      benzodiazepine use in the treatment of insomnia.

PMID- 11454124
TI  - Osteoporosis and depression: shedding more light upon a complex relationship.

PMID- 11454125
TI  - Urinary incontinence management: new questions from old assumptions.

PMID- 11454126
TI  - Improving quality in end-of-life care: dying at home.

PMID- 11454127
TI  - Improving the quality of end of life care: how?

PMID- 11454128
TI  - Correction. Hospitalization in the Program of All-Inclusive Care for the Elderly.

PMID- 11454129
TI  - In re preventing the spread of vancomycin-resistant enterococci in a long-term
      care facility.

PMID- 11454131
TI  - Goals of care for hospitalized nursing home residents.

PMID- 11454132
TI  - Herbal drug curbicin and anticoagulant effect with and without warfarin: possibly
      related to the vitamin E component.

PMID- 11454133
TI  - Outcomes of percutaneous endoscopic gastrostomy in dementia patients.

PMID- 11454134
TI  - In re hypertension and cognition: enough to be confused!

PMID- 11454136
TI  - Chronic myelogenous leukaemia--new therapeutic principles.
AB  - The deregulated tyrosine kinase activity of the BCR-ABL fusion protein is the
      cause of malignant transformation in almost all cases of chronic myelogenous
      leukaemia (CML), making BCR-ABL an ideal target for pharmacological inhibition.
      Signal transduction inhibitor (STI571) (formerly CGP57 148B), is an ABL specific,
      tyrosine kinase inhibitor. In preclinical studies, it has been shown to
      selectively kill BCR-ABL expressing cells, both in-vitro and in vivo. The results
      of clinical studies to date are highly encouraging and STI571 promises to be an
      important addition to the therapy of CML.

PMID- 11454137
TI  - Betablocker treatment in diabetes mellitus.
AB  - OBJECTIVES: Betablockers have been convincingly shown to reduce total and
      cardiovascular morbidity and mortality of hypertensive diabetic patients. In
      diabetic patients, after myocardial infarction, these agents confer a twice as
      high protective effect when compared to non-diabetic patients. However, most
      paradoxically, betablocking agents are used less frequently in diabetes. Control
      of hypertension is insufficient in most of the diabetic patients, probably
      because a combination of antihypertensive agents including betablockers is
      frequently needed to sufficiently control blood pressure but is not used in these
      patients. The fear of betablocker-associated side effects in diabetes may be
      partly responsible for the frequent antihypertensive mono-therapy and the
      resulting poor quality of blood pressure control among diabetic patients. DESIGN:
      We have performed an analysis of the literature to assess whether possible
      adverse metabolic effects, a higher risk of hypoglycaemia or less
      nephroprotective effects of beta1-selective betablocking agents could justify the
      reticence in prescribing these antihypertensive agents to diabetic patients.
      RESULTS: A thorough review of the literature does not indicate that beta1
      selective betablocking agents have important adverse effects on glucose
      metabolism, prolong hypoglycaemia or mask hypoglycaemic symptoms. In diabetic
      nephropathy, betablockers are as nephroprotective as angiotensin converting
      enzyme inhibitors. CONCLUSIONS: The unnecessary less frequent prescription of
      beta1-selective betablockers in diabetes mellitus may contribute to the higher
      cardiovascular mortality among these patients.

PMID- 11454138
TI  - Atrial fibrillation--Where do we stand today?
AB  - The basic underlying mechanisms behind atrial fibrillation (AF), the most
      abundant therapy demanding cardiac dysrhythmia, have until recently being largely
      unknown. Once established, AF is not only self-perpetuating but also self
      destructive, prompting rapid treatment against possible initiating mechanisms.
      Recent observations reveal that the ectopic beats, initiating AF, often originate
      in the walls of the pulmonary veins and that the deterioration of the ectopic
      impulse to AF may be linked to an impaired inferoposterior interatrial
      conduction. The underlying mechanisms behind these functional defects are still
      obscure. The observations has however, permitted evaluation of new types of
      treatment, directly interfering with the newly verified findings.

PMID- 11454139
TI  - Gender difference in age-related changes in vascular function.
AB  - PURPOSE: We investigated whether, in a randomly selected population of 55-year
      old men and women, there is a relationship between vascular function measured as
      flow-mediated (endothelium-dependent) and nitroglycerine-mediated (nonendothelium
      dependent) dilatation of the brachial artery and conventional risk factors for
      cardiovascular disease such as gender, smoking, elevated blood-lipids and high
      blood pressure. The results are compared with those in a young healthy population
      of 35-year-olds. SUBJECTS: A total of 57 men (73% of the invited males) living in
      the community and 47 women (62% of the invited females) participated and were
      compared with a previously studied 35-year-old population (52 men and 56 women).
      METHODS: Basal brachial artery diameter was measured by high-frequency ultrasound
      methods. Endothelial function was measured as flow-mediated dilatation (FMD) in
      response to reactive hyperaemia. The nonendothelium-dependent vasodilatation was
      measured after administering sublingual nitroglycerine (NTG). RESULTS: Flow
      mediated endothelium-dependent dilatation was similar in men and women being 3.1
      +/- 2.5% (mean +/- SD) in men vs. 2.6 +/- 2.3% in women. FMD of the brachial
      artery was negatively correlated with vessel size in both men and women (P <
      0.001). Men had larger brachial artery diameter than women (4.6 +/- 0.7 vs. 3.6
      +/- 0.4 mm, P < 0.001). There was no difference in FMD or in NTG-induced
      dilatation in the women receiving oral oestrogen replacement therapy compared
      with those that did not. The women taking oral oestrogen had lower cholesterol
      than those not taking oral oestrogen (P=0.04). FMD was not correlated with any of
      the risk factors. NTG-induced vasodilatation was correlated with the body mass
      index (BMI) in men (P=0.01) and a combined risk factor score in women (P=0.04).
      There was a large increase in the number of subjects with cardiovascular risk
      factors in the 55-year-old men and women compared with the 35-year-olds. The
      distribution of risk factors was fairly equal amongst men and women. CONCLUSION:
      There are no correlations between any of the conventional cardiovascular risk
      factors and FMD in a population of 55-year-olds, but there is a high prevalence
      of risk factors in the 55-year-old age group. NTG-induced vasodilatation
      correlated with the BMI in men and a combined risk-factor score in women. FMD
      induced vasodilatation is smaller in women at 55 years of age than at 35 years of
      age. FMD was similar in men at 35 and 55 years of age and in men and women at 55
      years of age. The smaller FMD in women at 55 years of age, compared with at 35,
      could be due to postmenopausal hormonal changes.

PMID- 11454140
TI  - Multiple endocrine neoplasia type 2 syndromes may be associated with renal
      malformations.
AB  - OBJECTIVE: The RET proto-oncogene is known to be the susceptibility gene for
      various disease phenotypes, including multiple endocrine neoplasia type 2 (MEN
      2). Recent studies have also suggested an involvement of RET in the development
      of the mammalian kidney. Although kidney agenesis or dysgenesis has been observed
      in mice lacking functional ret, no clinically relevant kidney abnormalities have
      been reported in individuals with known RET mutations and familial medullary
      thyroid carcinoma (FMTC). We have studied a family with five members affected
      with isolated FMTC. DNA analysis was performed and the involved RET mutation was
      identified. Amongst these patients were a woman and her son. DESIGN: Case report.
      SETTING: University department. PATIENTS: A 32-year-old woman and her son with
      FMTC and unilateral renal agenesis. RESULTS: The woman's abdominal ultrasound
      findings demonstrated unilateral renal absence of the left kidney. Her son, when
      only a few months old, had undergone surgical treatment for Hirschsprung's
      disease. Abdominal ultrasonography was performed recently, and left-side renal
      absence was diagnosed. Intravenous pyelography confirmed the agenesis of his left
      kidney, whilst the contralateral kidney displayed compensatory hypertrophy.
      CONCLUSIONS: The involvement of the RET proto-oncogene in the early growth and
      differentiation of the human kidney is now generally accepted. We believe that at
      least a proportion of patients with MEN 2 may have undiagnosed renal
      malformations. We suggest therefore that noninvasive imaging techniques, such as
      ultrasonography, should be used to explore the presence of renal abnormalities in
      subjects with demonstrated RET mutations.

PMID- 11454141
TI  - Childbearing and the risk of parathyroid adenoma--a dominant cause for primary
      hyperparathyroidism.
AB  - OBJECTIVES: To explore possible associations between the reproductive history
      amongst women and the risk of parathyroid adenoma (PA). DESIGN: Two nationwide
      Swedish registries. The Fertility Register included data on more than 3.4 million
      livebirths between 1943 and 1992 amongst Swedish females born 1925-72. The Cancer
      Register encompasses more than 1800 women with a diagnosis of PA 1960 until 1992.
      SETTING: All women resident in Sweden 1960-92. SUBJECTS: Cases were all 1800
      women born 1925-72 reported to the Swedish Cancer Registry with a
      histopathological diagnosis of PA. Five controls were selected at random for each
      case by matching for the month and year of birth. Conditional logistic regression
      was used to estimate relative risks of PA. MAIN OUTCOMES: Parathyroid adenoma.
      RESULTS: High parity (four or more live births) was associated with an increased
      risk of PA. Amongst women with a diagnosis of PA before menopause (i.e. the age
      of 50 years) there was an increased risk of PA with younger age at first
      childbirth. Nulliparous women were at increased risk for PA before menopause, and
      at decreased risk after menopause. CONCLUSIONS: There is an association between
      childbearing and the risk of PA, which has not previously been demonstrated, but
      the underlying biological mechanisms remain to be determined.

PMID- 11454142
TI  - Increased bone mineral density in a population-based group of 70-year-old women
      on thiazide diuretics, independent of parathyroid hormone levels.
AB  - BACKGROUND: Several studies have shown greater bone mineral density (BMD) in
      people receiving thiazide diuretics compared with controls. Most researchers have
      related this association to the hypocalciuric effect of thiazides with subsequent
      rise in serum calcium and fall in parathyroid hormone (PTH) levels. Recent
      experimental evidence suggests, however, a direct effect of thiazides on
      osteoblast-like cells. OBJECTIVE: To test the hypothesis that the association of
      thiazides and raised BMD is independent of PTH levels in humans. SUBJECTS: A
      population-based group of 248 70-year-old Icelandic women, 51 receiving thiazide
      diuretics, 39 receiving other antihypertensive therapy and the rest acting as
      controls. MAIN OUTCOME MEASURES: The independent contribution of thiazide usage
      and PTH to BMD in a multivariate analysis. RESULTS: The mean BMD was 9.6% greater
      in the lumbar spine (P < 0.01) and 5.4% greater in the whole skeleton (P < 0.01)
      amongst thiazide users than in controls, reduced to 7.6% (P < 0.02) and 4.5% (P <
      0.01), respectively, when corrected for fat mass which was 5.8 kg greater in the
      thiazide group. In a multivariate analysis, corrected for body weight and body
      composition, serum calcium and ln-PTH, thiazides remained a significant
      independent predictor of BMD in the total skeleton and lumbar spine, but not in
      the total hip or femoral neck. Thiazides explained about 3% of the variability in
      whole body and lumbar spine BMD. CONCLUSIONS: Thiazides augment or preserve BMD
      independent of PTH, implying other mechanisms.

PMID- 11454143
TI  - Cost of illness of adult diabetes mellitus underestimated if comorbidity is not
      considered.
AB  - OBJECTIVE: To determine costs of illness for adult diabetes mellitus (DM),
      including complications caused by DM. DESIGN: A population-based multicentre
      cross- sectional study including an interview and a physical examination of
      patients identified as having DM. The patients' medical records were analysed
      regarding diagnoses and complications attributable to DM. SETTING: Eight health
      care centres of six primary care districts in Southern Sweden. SUBJECTS: 1677
      adults aged 25+, cared for at the health care centres, entered the study. MAIN
      OUTCOME MEASURES: Utilization of health care and care from relatives and the
      municipality, absence of short- and long-term sickness, cost of illness. RESULTS:
      The average annual direct and indirect costs for an adult with DM were calculated
      to be 61 700 Swedish Kronor (SEK) or 2.5 times higher than earlier estimates. The
      incremental cost of DM was 34 100 SEK. The cost distribution was 28% for health
      care, 31% for the municipality and relatives and 41% lost productivity.
      CONCLUSIONS: Calculations for the cost of illness of DM are underestimated if
      comorbidity caused by DM is not considered. When DM-related complications are
      included to identify the actual burden of disease to society, the cost of illness
      as a result of DM in Sweden is substantially higher than previously estimated.

PMID- 11454144
TI  - Chlamydia pneumoniae and luminal narrowing after coronary angioplasty.
AB  - OBJECTIVES: Numerous studies have linked Chlamydia pneumoniae with
      atherosclerotic vessel disease and a trend for an association of the bacteria
      with restenosis after percutaneous transluminal coronary angioplasty (PTCA) has
      also been observed. The aim of this study was to assess the role of Chlamydia
      pneumoniae in the luminal narrowing taking place after PTCA. DESIGN: A
      noninterventional 6-month follow-up study. SETTING: A university hospital.
      SUBJECTS: A total of 122 patients with angiographically proven coronary heart
      disease (CHD) referred for PTCA. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The
      degree of luminal narrowing in the coronary arteries following coronary
      angioplasty. RESULTS: The levels of C. pneumoniae antibodies (IgG, IgA and IgM
      classes) and immune complexes were not associated with luminal narrowing after
      PTCA in multivariate analyses whilst smoking, plasma endothelin levels and
      diabetes were. The serologic parameters did not change during the follow up
      either. CONCLUSIONS: These results do not support a role for C. pneumoniae in
      luminal narrowing following PTCA.

PMID- 11454145
TI  - Hypercalcaemia of malignancy: an undiagnosed and undertreated disease.
AB  - BACKGROUND: Hypercalcaemia of malignancy, a relatively frequent phenomenon, seems
      to be insufficiently recognized and treated. Its symptoms are not specific, but
      they affect the quality of life. METHODS: A prospective study to analyse the
      influence of symptoms caused by hypercalcaemia on the decision of the admitting
      physician, the motivation for treatment, and the effect of the treatment on the
      given symptoms in hospitalized patients with oncologic disease in progression,
      where confounding causes of similar symptoms such as cerebral metastasis,
      radiotherapy, treatment with opioids, etc., were excluded. RESULTS: A total of 71
      patients, mean age 65 + 11 years, fulfilled the strict inclusion criteria. About
      42% were hospitalized because of symptoms caused by hypercalcaemia, but none of
      the medical reports mentioned hypercalcaemia as reason for hospitalization.
      Specific antihypercalcaemic therapy was given to only 37% of patients, and only
      25% got an adequate rehydratation. Antihypercalcaemic treatment was guided by the
      severity of hypercalcaemia (>3.00 mmol L(-1)), not by the symptoms. Polyuria
      polydipsia, nausea-vomiting and constipation were correlated with hypercalcaemia.
      These symptoms, as well as confusion-stupor and bone pains improved significantly
      when calcaemia was normalized. Patients with calcaemia normalized returned home
      most frequently (P < 0.03). CONCLUSIONS: Malignant hypercalcaemia remains mostly
      undiagnosed in medical praxis. Specific treatment occurs in too small fractions
      of the patients. As the normalization of calcaemia significantly improves the
      symptoms because of hypercalcaemia and the quality of life, rapid rehydration and
      specific calcium lowering treatments should be part of palliative measures in all
      patients with malignant hypercalcaemia.

PMID- 11454146
TI  - Antidiabetogenic action of glucagon-like peptide-1 related to administration
      relative to meal intake in subjects with type 2 diabetes.
AB  - OBJECTIVE: To establish the antidiabetogenic effect of glucagon-like peptide-1
      (GLP-1) when differently administered relative to meal intake in subjects with
      type 2 diabetes. DESIGN: The study was a placebo-controlled comparison with
      random assignment to treatment sequence. A 3-h stepwise infusion of GLP-1 (17
      nmol) was started either at the onset of a standard meal (550 kCal) (A) or at 30
      min (B) or 60 min (C) after the start of the meal. SETTING: The study was
      conducted at a university hospital. SUBJECTS: Eight patients with type 2 diabetes
      (four women and four men), age 62 +/- 3.9 years (range 47-74 years), weight 79.8
      +/- 5.4 kg (range 62-104 kg), BMI 26.2 +/- 1.3 kg m(-2) (range 21-31 kg m(-2)),
      diabetes duration 10.5 +/- 2.0 years (range 3-19 years) and HbA1c levels 6.1 +/-
      0.3% (range 4.7-7.7%) participated in the study. All patients were treated with
      oral sulphonylureas. RESULTS: Glucagon-like peptide-1 significantly lowered
      postprandial glycaemia by a similar degree in all three situations versus the
      control meal (P < 0.05). Postprandial insulin levels were not different in the
      four experimental series, whereas the postprandial glucagon levels were
      significantly lowered by GLP-1 in (A) and (B) (P < 0.03) but not in (C). Gastric
      emptying, as determined by the paracetamol test, was retarded by GLP-1 only in
      (A) (P < 0.01), but not affected in (B) or (C). CONCLUSIONS: GLP-1 reduced
      postprandial hyperglycaemia in subjects with type 2 diabetes regardless of
      administration at the onset of meal intake or at 30 or 60 min after start of meal
      intake, although the mechanism of the antidiabetogenic action of GLP-1 depended
      on administration versus meal intake. Thus, when administered at the start of a
      meal, GLP-1 was antidiabetogenic mainly through retarding gastric emptying,
      whereas when given at 30 or 60 min after meal ingestion, changes in islet hormone
      secretion seem to be predominant.

PMID- 11454148
TI  - In situ observation of oxygen deficiency occurring during electron irradiation in
      high Tc superconductor YBa2Cu3Oy.
AB  - The decreasing process of oxygen in YBa2Cu3Oy is investigated through high
      resolution electron microscopy (HREM) and convergent beam electron diffraction
      (CBED). Measurements of the axial length in HREM images show that oxygen content
      y decreases faster near a twin boundary than at the inner part of a twin lamella.
      The transformation from an orthorhombic to a tetragonal phase starts at a twin
      boundary and the transformed region propagates to an inner region of lamella.
      Lattice strains are observed near boundaries between transformed and non
      transformed regions. The transformation is almost complete within 30 s during
      observation of HREM images at 400 kV and at room temperature. A value of y was
      quantitatively measured by analysing observed intensities of energy-filtered CBED
      patterns with the dynamical theory. The value of y decreases from 6.9 to 6.5 when
      200 kV electrons are irradiated for 160 s in a microscope at 108 K. More precise
      analysis of the intensities provides information on charge distribution along the
      c-axis as well as local oxygen content at a spatial resolution of several
      nanometres.

PMID- 11454149
TI  - Dynamic chemical mapping near a Si/SiO2 interface at elevated temperatures using
      plasmon-loss images.
AB  - Plasmon-loss imaging was applied to chemical mapping during an in-situ heating
      experiment. The technique was applied to observation of vibration of a Si/SiO2
      interface which took place during reduction of SiO2 at high temperature. The
      chemical maps of Si and SiO2 were recorded dynamically using a conventional TV
      VTR system at a time resolution of 1/30 s.

PMID- 11454150
TI  - In situ high resolution electron microscopy/electron energy loss spectroscopy
      observation of wetting of a Si surface by molten Al.
AB  - Electron energy loss spectroscopy was used to observe the segregation of Al on a
      Si surface above the melting point of Al. A mixture of Al and Si particles was
      heated above the melting point of Al in a vacuum of 1 x 10(-5) Pa. The Si
      surface, which initially had been covered with an amorphous oxide layer before
      heating, became clean and atomically facetted when the Al melted. It was shown
      that the Si surface was segregated with Al.

PMID- 11454151
TI  - Precursor effects of martensitic transformations in Ti-based alloys studied by
      electron microscopy with energy filtering.
AB  - Precursor effects of martensitic transformations in two well-known shape memory
      alloys, Ti50Ni48Fe2 and Ti50Pd34Fe16, were studied extensively by energy-filtered
      electron microscopy, including in-situ observations, and high-resolution electron
      microscopy. Energy-filtered dark-field images, where weak diffuse scattering was
      utilized, clearly showed the microstructure in the premartensitic state of
      Ti50Ni48Fe2. Tiny domains observable in this state were close to spherical rather
      than thin and slender, and the temperature dependence of the domain-like
      structure was clarified by the in-situ observations. It was found that
      Ti50Pd34Fe16 exhibited a domain-like structure similar to that of Ti50Ni48Fe2,
      which was attributed to a transverse lattice displacement. High-resolution images
      of Ti50Pd34Fe16 showed that a domain was coupled with other ones with different
      orientations of distortion, so as to reduce the total strain due to their
      formations. Furthermore, effects of including a fundamental reflection, in
      addition to the diffuse scattering, on dark-field images were discussed based on
      the observations and the image processing.

PMID- 11454152
TI  - Direct observation of a Ti/Cu interface with atomic displacement under electron
      irradiation.
AB  - A Ti film was deposited onto a Cu substrate by means of a radio frequency
      magnetron sputtering METHOD: Cross-sectional thin foils for TEM observation were
      prepared using a focused ion beam. Electron irradiation was carried out using a
      high-resolution high-voltage electron microscope operated at 1.25 MV. The Cu/Ti
      interface of the foils was irradiated at 623 K. In-situ observation images during
      electron irradiation were recorded by a CCD camera with a digital video cassette.
      The (020)Cu plane on the Cu/Ti interface preferentially moved towards the Ti film
      with irradiation. Composition analysis of the diffused region showed that its
      composition corresponded to Ti3Cu2.

PMID- 11454153
TI  - In situ observation of the initial growth process of carbon nanotubes by time
      resolved high resolution transmission electron microscopy.
AB  - We succeeded in plan-view dynamic observation of the initial formation process of
      carbon nanotubes from beta-SiC( 1 1 1) surfaces by time-resolved high resolution
      transmission electron microscopy. At 1360 degrees C, the flakes of graphite
      layers of a fibre orientation were formed on the SiC( 1 1 1) surfaces. From the
      graphite layers, carbon nanotubes were formed perpendicular to the ( 1 1 1) plane
      of the SiC. A scanning tunnelling microscopy observation showed that the end of
      carbon nanotube was closed. These results indicate that the caps of the carbon
      nanotubes are formed by a lift of a part of the graphene along the [ 1 1 1]
      direction of the SiC through generation of pentagons and heptagons. Two types of
      carbon nanotube, single-wall and double-wall, were observed in plan-view images.
      Different image intensity between an outer ring and an inner ring in double-wall
      nanotubes suggests that the inner layers of multiwall nanotubes are formed after
      the outer ones.

PMID- 11454154
TI  - Quantitative measurements in in situ straining experiments in transmission
      electron microscopy.
AB  - Several examples of recent studies by in situ straining experiments in a
      transmission electron microscope performed in the Toulouse group (France) are
      presented. In particular, quantitative measurements of the features of the
      dislocation motion are described. These examples deal with individual or
      collective propagation of dislocations, which are submitted to various types of
      obstacle. Different metallic materials are investigated: magnesium,
      intermetallics, aluminium alloys and gamma phase of a superalloy.

PMID- 11454155
TI  - In situ observation of superdislocation motion in pre-strained Ni3Ge single
      crystals.
AB  - Dislocation structures and their effect on the superdislocation motion in Ni3Ge
      single crystals have been studied by two-step deformation. In these tests either
      octahedral or cube slips were induced by prestraining. A difference in the
      induced dislocation structure is found to cause a notable change in the second
      deformation step depending on the combination of the stress axes. In order to
      understand the orientation sensitive hardening, in-situ deformation experiments
      have been made on the prestrained specimens in a high voltage electron
      microscope. Besides observation of the structural change due to dislocation
      motion, electron irradiation, which decorates antiphase boundary tubes, is
      utilized to trace the history of the rapid dislocation motion. Based on these
      observations, the origin of the anomalous strengthening in Ni3Ge is discussed
      with particular interest in the fine and non-planar dislocation structures
      induced by cross slips and dislocation-dislocation interactions.

PMID- 11454156
TI  - High-voltage electron microscope high-temperature in situ straining experiments
      to study dislocation dynamics in intermetallics and quasicrystals.
AB  - The dynamic behaviour of dislocations in several intermetallic alloys, studied by
      in situ straining experiments in a high-voltage electron microscope, is compared
      at room temperature and at high temperatures. In contrast to room temperature,
      the dislocations move viscously at high temperatures, which is explained by
      diffusion processes in the dislocation cores. In quasicrystals, the viscous
      dislocation motion can be interpreted by models on the cluster scale.

PMID- 11454157
TI  - Dislocation mobility and electronic effects in semiconductor compounds.
AB  - In situ transmission electron microscopy experiments provide a unique way to
      investigate in real time the dislocation behaviour at a microscopic scale and to
      decide which elementary process controls the dislocation glide in semiconductors.
      In this review the experimental results obtained on different semiconductors are
      presented and discussed. Particular attention is devoted to the radiation
      enhanced glide process.

PMID- 11454158
TI  - Is plastic flow always controlled by dislocation mobility? An answer from in situ
      transmission electron microscopy straining tests.
AB  - In situ transmission electron microscopy (TEM) straining experiments are used to
      illustrate in two extreme cases the possible role of dislocation nucleation and
      exhaustion as a controlling factor in plastic flow. In the first example (FeAl
      intermetallic compounds), a thermally activated dislocation exhaustion is
      responsible for an anomalous stress-temperature dependence and an associated
      small strain rate sensitivity, the latter being evidenced during in situ
      experiments through unstable localized slip. The second example (heavily drawn
      pearlite) shows specific dislocation loop nucleation processes that may account
      for the Hall-Petch law breakdown characteristic of fine scale nanostructures.

PMID- 11454159
TI  - In situ observations of unusual dislocation mechanisms in the intermetallic alloy
      Ti3Al.
AB  - In situ straining experiments in a transmission electron microscope have been
      carried out on a Ti3Al intermetallic alloy, with the aim of determining the
      microscopic mechanisms controlling glide in prism, basal and pyramidal planes.
      Five different antiphase boundary energies have been measured and compared with
      the corresponding densities of incorrect first nearest neighbour atoms. The
      determination of a tension-compression asymmetry in pyramidal slip, and the
      detailed analysis of the complex microscopic mechanisms involved illustrate the
      efficiency of in situ experiments to solve complex problems in plasticity. A
      comparison between the properties of the different slip systems shows that they
      are controlled by different microscopic mechanisms, none of them being of
      covalent origin.

PMID- 11454160
TI  - Atomic force microscopy observations of in situ deformed materials: application
      to single crystals and thin films on substrates.
AB  - An experimental apparatus which consists of a compression machine interfaced with
      an atomic force microscope has been realized and allows the in situ observation
      of a sample surface under compressive stress. Taking advantage of the high
      resolution offered by this microscopy, the equipment is particularly suited both
      to analysing the fine slip line structure of deformed single crystals, providing
      interesting complementary information about plastic mechanisms taking place in
      the bulk, and to characterizing the mechanical behaviour of thin films on
      substrates with the investigation of the buckling phenomenon.

PMID- 11454161
TI  - In situ optical microscopic recording of slip line development during plastic
      deformation of Cu-15at%Al single crystals with high resolution--estimation of
      dislocation velocities.
AB  - Observations and measurements of slip line evolution during plastic deformation
      are performed by optical microscopic video recording. In addition, high
      resolution in time is achieved by means of photodiodes positioned in the
      intermediate image plane of the microscope. Examples of measurements at room
      temperature on short-range ordered Cu-15at%Al single crystals are given and
      evaluated to estimate the velocities of edge and screw dislocation groups from
      the observed rates of growth of slip steps in height and in length, respectively,
      on one side of the specimen. By means of a second microscope observing the
      opposite side, the average rates for the dislocations to cross the whole specimen
      can be obtained. The measured values are discussed in terms of the movement of
      correlated dislocation groups in the crystals.

PMID- 11454162
TI  - In situ observation and interferometric characterization of solid-liquid
      interface morphology in directionally growing transparent model systems.
AB  - The performance of a new directional solidification device dedicated to the
      characterization of solid-liquid interface morphology by means of optical methods
      is presented in this paper. In contradiction to usual solidification studies on
      transparent materials carried out on thin films, which eliminates the complex
      coupling between solidification and convection, this device enables in situ and
      real time studies on bulk transparent materials. The alloy is contained in a
      cylindrical crucible and observation is performed in two perpendicular
      directions: the growth one and the transverse one. In addition to direct
      observation by light transmission in those directions, an interferometer is also
      set up in the growth direction to provide information on the shape and the motion
      of the interface through an analysis of the interferometer fringes. The combined
      determination of solidification front characteristics by these three observation
      modes has already given critical information on interface dynamics: front recoil
      measurements during initial transient, formation of microstructure patterns, and
      influence of convection on the triggering of instabilities.

PMID- 11454163
TI  - In situ transmission electron microscopy studies and real-time digital imaging.
AB  - A newly designed CCD camera has been utilized for real-time and static image
      acquisitions. The performance of the camera is demonstrated for heating/cooling
      in-situ TEM experiments performed on a commercial high strength aluminium alloy
      using a double tilt heating holder. The real-time digital imaging capability of
      the new camera should facilitate the in-situ TEM that is now re-establishing
      itself as a strategic tool for materials characterization.

PMID- 11454164
TI  - Synthesis and biological evaluation of destruxin A and related analogs.
AB  - This report describes the development of an efficient solid-phase synthesis
      protocol and adaptation of reported solution phase procedures for the synthesis
      of the cyclic depsihexapeptide destruxin A and related analogs. The solid-phase
      method described is based on standard Fmoc peptide chemistry, including a new
      synthetic method for the assembly of the depsi bond-containing unit. In order to
      select analogs of destruxin A for synthesis and evaluation of insecticidal
      activity, the work of Hellberg et al., describing a set of Z-descriptors for
      amino acid side-chains comparing their physicochemical properties, was utilized.
      Destruxin A and 27 different analogs with structural variations in four residues
      were synthesized and insecticidal activity was evaluated via injections into
      tobacco budworm (Heliothis virescens) larvae. Several destruxin A analogs were
      found to be at least as potent as the native compound.

PMID- 11454165
TI  - Enzymatic synthesis of chromogenic substrates for Glu,Asp-specific proteinases.
AB  - Glu,Asp-specific endopeptidases represent a new subfamily of chymotrypsin-like
      proteolytic enzymes. These enzymes prefer Glu or Asp residues in the P1 position
      of the substrates. p-Nitroanilides of N-acylated di-, tri- and tetrapeptides with
      C-terminal glutamic or aspartic acid residues have been obtained. Acyl peptide p
      nitroanilides were synthesized via acylation of glutamic or aspartic acid p
      nitroanilides using methyl esters of the respective N-acylated peptides,
      generally with good yields. The reactions were performed in organic solvents
      using subtilisin 72 sorbed on silica as a catalyst. The kinetic parameters for
      the hydrolysis of these p-nitroanilides with proteinases from Bacillus
      intermedius and Bacillus licheniformis were determined.

PMID- 11454166
TI  - Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using
      disulfide peptides of its beta-subunit: possible involvement of the disulfide
      bonds Cys(9)-Cys(57) and Cys(23)-Cys(72) in receptor binding of the hormone.
AB  - Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone
      essential for the establishment and maintenance of pregnancy. The alpha- and beta
      subunits of hCG are highly cross-linked internally by disulfide bonds which seem
      to stabilize the tertiary structures required for the noncovalent association of
      the subunits to generate hormonal activity. The purpose of this study was to
      delineate the role of the disulfide bonds of hCGbeta in receptor binding of the
      hormone. Six disulfide peptides incorporating each of the six disulfide bonds of
      hCGbeta were synthesized and screened, along with their linear counterparts, for
      their ability to competitively inhibit the binding of [125I] hCG to sheep ovarian
      corpora luteal LH/CG receptor. Disulfide peptide Cys (9-57) was found to be
      approximately 4-fold more potent than the most active of its linear counterparts
      in inhibiting radiolabeled hCG from binding to its receptor. Similarly, disulfide
      peptide Cys (23-72) exhibited receptor binding inhibition activity, whereas the
      constituent linear peptides were found to be inactive. The results suggest the
      involvement of the disulfide bonds Cys(9)-Cys(57) and Cys(23)-Cys(72) of the beta
      subunit of hCG in receptor binding of the hormone. This study is the first of its
      kind to use disulfide peptides rather than linear peptides to map the receptor
      binding regions of hCG.

PMID- 11454167
TI  - A new insect neurotoxin AngP1 with analgesic effect from the scorpion Buthus
      martensii Karsch: purification and characterization.
AB  - An insect toxin named BmK AngP1 was purified from the venom of the scorpion
      Buthus martensii Karsch (BmK). It also shows an evident analgesic effect on mice,
      but is interestingly devoid of mammalian toxicity. Bioassay showed that the CPU
      value of AngP1 was 0.01 microg/body ( approximately 30 mg) for the excitatory
      insect toxicity and 43.0% inhibition efficiency for analgesia at a dose of 5
      mg/kg. However, even at the dosage of 10 mg/kg no detectable toxicity on mice
      could be found. The isoelectric point (pI) value for AngP1 was 4.0, and its
      molecular mass analyzed by MALDI-TOF MS was 8141.0. The first 15 N-terminal
      residues of AngP1 were determined by Edman degradation and showed high similarity
      to that of other excitatory scorpion insect toxins. The circular dichroism
      spectroscopy measured on a JASCO J-720 system showed that there were 10.4% alpha
      helix, 46.2% beta-strand and 14.1% turn structure in this peptide. Under two
      conditions single crystals of AngP1 were obtained.

PMID- 11454168
TI  - Systematic solid-phase synthesis of linear pseudooligolysines containing multiple
      adjacent CH(2)NH amide bond surrogates: potential agents for gene delivery.
AB  - Solid-phase methodology was used to synthesize a series of fully reduced linear
      oligolysines (pseudooligolysines, abbreviated herein as PLs) containing up to
      five adjacent CH2NH peptide bond isosteres. The reduced peptide bonds were
      introduced by the reductive alkylation reaction between Fmoc-Lys-(Boc)-al and a
      free alpha-amine moiety on the pseudopeptidyl resin, using sodium
      cyanoborohydride in an acidified mixture of NMP/CH3OH (1 : 1 v/v). The oligomeric
      molecules, which can be regarded as polyethylene imine and spermine analogs,
      possess multiple positive charges under physiological conditions and form tight
      complexes with plasmid DNA. These characteristics and the increased resistance to
      hydrolysis by trypsin make these molecules potential candidates for future use as
      DNA carriers in gene delivery.

PMID- 11454169
TI  - Molecular dynamics simulation of the antimicrobial salivary peptide histatin-5 in
      water and in trifluoroethanol: a microscopic description of the water
      destructuring effect.
AB  - The results of 520 ps molecular dynamics simulation of histatin-5, a small
      peptide present in human saliva and possessing antimicrobial activity, dissolved
      in water and in 2,2,2-trifluoroethanol, are reported. The simulations indicate
      that histatin-5 is destabilized in water and begins to unfold after 250 ps, while
      in organic solvent it maintains a regular secondary structure throughout the
      trajectory. Analysis of the peptide-solvent hydrogen bonds indicates that 2,2,2
      trifluoroethanol is a poorer proton acceptor than water. The fluorine atom of the
      alcohol is almost never engaged in a hydrogen bond and the organic solvent
      interacts mainly with the peptide through its hydroxyl group. For some residues
      analysis of the solvent residence time indicated longer values for 2,2,2
      trifluoroethanol than for water. The most striking difference is related to the
      number of times the solvent enters and leaves the first coordination shell of the
      peptide. This value was more than one order of magnitude higher for water than
      for the alcohol, suggesting that this may be the main cause of alpha-helix
      destabilization perpetrated by water.

PMID- 11454170
TI  - Pseudopeptides containing the 2-hydrazonoacyl fragment: analogs of the
      chemotactic agent HCO-Met-Leu-Phe-OMe.
AB  - In order to further examine the properties of pseudopeptides containing the 2
      hydrazonoacyl fragment, two new series of analogs of the prototypical chemotactic
      N-formyl-tripeptide HCO-Met-Leu-Phe-OMe were designed and synthesized. The first
      group contains the new fragment as the N-terminal residue and is represented by
      the N-aryl derivatives p-Cl-C6H4-NH-N=C(R)-CO-Leu-Phe-OMe (2 and 3) and by the
      corresponding N-aroyl analogs p-CH3-C6H4-CO-NH-N=C(R)-CO-Leu-Phe-OMe (4). The
      second group contains the new fragment in place of the central Leu residue and is
      represented by compounds HCO-Xaa-NH-N=C(R)-CO-Phe-OMe (7a and 7b) where Xaa is
      Nle and Met, respectively. The conformational and biochemical properties of the
      new products were examined.

PMID- 11454171
TI  - Synthesis, X-ray crystallographic structures of thio substituted N-acetyl N'
      methylamide alanine and evaluation of sp sulfur parameters of the CFF91 force
      field.
AB  - Acetyl thioalanine N-methyl (Ac-Alat-NHMe) and thioacetyl alanine N-methyl (Act
      Ala-NHMe) were synthesized, crystallized and their X-ray diffraction structures
      determined for the first time. Both molecules adopted beta-sheet conformations
      and showed similar hydrogen bonding patterns with one molecular surface forming
      two oxo hydrogen bonds and the other forming two thio hydrogen bonds. The crystal
      structure data for the two thioamides provided a validation of the thioamide
      parameters for the newly derived CFF91 force field because the observed crystal
      (phi, psi) angles were situated in the global minimum regions of the theoretical
      (phi, psi) map predicted using the parameters. In addition, the parameters were
      further validated because conformational energy minimization of the crystal
      structure produced low deviations in unit cell dimensions, bond lengths, bond
      angles and torsional angles, and a 120-ps molecular dynamics simulation also gave
      a low deviation for the most probable N-H...S=C bond distance.

PMID- 11454172
TI  - Structures of the transmembrane helices of the G-protein coupled receptor,
      rhodopsin.
AB  - An hypothesis is tested that individual peptides corresponding to the
      transmembrane helices of the membrane protein, rhodopsin, would form helices in
      solution similar to those in the native protein. Peptides containing the
      sequences of helices 1, 4 and 5 of rhodopsin were synthesized. Two peptides, with
      overlapping sequences at their termini, were synthesized to cover each of the
      helices. The peptides from helix 1 and helix 4 were helical throughout most of
      their length. The N- and C-termini of all the peptides were disordered and
      proline caused opening of the helical structure in both helix 1 and helix 4. The
      peptides from helix 5 were helical in the middle segment of each peptide, with
      larger disordered regions in the N- and C-termini than for helices 1 and 4. These
      observations show that there is a strong helical propensity in the amino acid
      sequences corresponding to the transmembrane domain of this G-protein coupled
      receptor. In the case of the peptides from helix 4, it was possible to
      superimpose the structures of the overlapping sequences to produce a construct
      covering the whole of the sequence of helix 4 of rhodopsin. As similar
      superposition for the peptides from helix 1 also produced a construct, but
      somewhat less successfully because of the disordering in the region of sequence
      overlap. This latter problem was more severe for helix 5 and therefore a single
      peptide was synthesized for the entire sequence of this helix, and its structure
      determined. It proved to be helical throughout. Comparison of all these
      structures with the recent crystal structure of rhodopsin revealed that the
      peptide structures mimicked the structures seen in the whole protein. Thus
      similar studies of peptides may provide useful information on the secondary
      structure of other transmembrane proteins built around helical bundles.

PMID- 11454173
TI  - Viral hepatitis and primates: historical and molecular analysis of human and
      nonhuman primate hepatitis A, B, and the GB-related viruses.
AB  - The hepatitis viruses have long been assumed to be highly host-specific, with
      infection of other nonhuman primates occurring due to inoculation with, or
      exposure to, human viruses. This paradigm has slowly changed over the last 10
      years, as mounting data has revealed nonhuman primate equivalents of hepatitis A
      virus, hepatitis B virus, and the hepatitis C-related viruses GBV-C and GBV-A.
      This review summarizes the historical and molecular information for each of these
      groups and highlights the impact of these nonhuman primate hepatitis viruses on
      our understanding of the evolution of each of these viruses.

PMID- 11454174
TI  - NS5A mutations predict biochemical but not virological response to interferon
      alpha treatment of sporadic hepatitis C virus infection in European patients.
AB  - The NS5A region of the hepatitis C virus (HCV) genome has been reported by
      Japanese but not European investigators to be a significant factor in predicting
      interferon (IFN) response patients with HCV of genotype 1. We correlated the NS5A
      region with treatment outcome in patients with sporadic HCV infection. Twenty
      eight patients (10 men, 18 women, mean age 60 +/- 2 years) with histologically
      proven HCV chronic hepatitis, genotype 1b, were treated with 6 MU IFN-alpha for 6
      months. The 6954-7073 area of the NS5A region was directly sequenced for
      nucleotide and amino acids mutations and the results were related to biochemical
      and virological response. None of the patients had a strain with nucleotide
      sequence identical to the Japanese HCV-J. However, in five strains the nucleotide
      mutations led to synonymous amino acids and the amino acid sequences were
      identical to the prototype Japanese strain. Only 2/28 patients had four or more
      amino acid mutations (mutant strains) while 21 demonstrated an intermediate type
      and five belonged to the wild-type. The most frequent non-synonymous substitution
      was at position 6982 (A-->G) corresponding to an amino acid change at codon 2218
      (His-->Arg). All patients with the wild-type were biochemical nonresponders while
      the two patients with the mutant strains had a sustained biochemical response.
      Twenty-three percent of the intermediate type had a sustained biochemical
      response. NS5A mutations predict the biochemical but not the virological response
      of patients. Virological response was poor and unrelated to the type of HCV
      strain. Biochemical responders had significantly lower amino acid mutations (1.14
      +/- 0.19) compared with nonresponders (2.57 +/- 1.4, P < 0.003) as well as lower
      aminotransferase values (P < 0.01). Hence, mutational analysis of the NS5A region
      showed that our patients have a mutational profile similar to the European
      studies with a wild-type that is slightly different from the Japanese HCV-J
      sequence. The biochemical, but not the virological response to IFN-alpha is
      similar to the Japanese studies, with no response of the patients with wild-type
      sequence, a good response in the limited number of patients with mutant strains
      and 23% response rate in the patients with intermediate type sequences.

PMID- 11454175
TI  - Historical features are poor predictors of liver fibrosis in Canadian patients
      with chronic hepatitis C.
AB  - The progression of fibrosis in chronic hepatitis C infection (HCV) is related to
      host factors including age, gender and alcohol consumption. Due to the morbidity
      and potential mortality of liver biopsy, a noninvasive method of assessing
      hepatic fibrosis is needed. The aim of this study was to assess the utility of
      historical features in predicting fibrosis using published rates of fibrosis
      progression. The charts of 239 untreated patients with HCV were reviewed;
      patients who had a liver biopsy and whose duration of infection could be
      estimated (n=106) were categorized according to gender, age at infection (< or =
      or > 40 years) and peak alcohol consumption (< or > or = 50 g/day). Estimates of
      fibrosis were calculated using the product of the interval between infection and
      biopsy and published rates of fibrosis progression. Estimates were compared with
      liver biopsies staged according to the Metavir system (F0-F4; F0=no fibrosis; F4=
      cirrhosis). The mean age of patients was 42 +/- 8 years, 61% were male and 36%
      consumed > 50 g of alcohol daily. The mean duration of infection was 19 +/- 9
      years (range, 1-40) and ALT was elevated > 1.5 times upper normal in 63%. When
      patients were classified into those with mild (F0-F2) and severe (F3-F4)
      fibrosis, the sensitivity, specificity, positive predictive value and negative
      predictive value of an estimate of mild fibrosis was 60%, 55%, 78% and 34%,
      respectively. An estimate of severe fibrosis had a sensitivity of 55%,
      specificity of 60%, positive predictive value of 34% and negative predictive
      value of 78%. Agreement between fibrosis estimates and actual histological stages
      was poor (kappa = 0.13, P=0.08). The prediction of hepatic fibrosis in HCV
      infection using historical features and published rates of fibrosis progression
      is poor in a Canadian clinical practice setting. Alternate noninvasive methods of
      predicting hepatic fibrosis are needed.

PMID- 11454176
TI  - Stability of HCV-RNA level and its lack of correlation with disease severity in
      asymptomatic chronic hepatitis C virus carriers.
AB  - This study examines the relationship between HCV-RNA levels and disease severity
      in 60 individuals with chronic hepatitis C virus infection. HCV-RNA levels were
      quantified by the branched DNA (bDNA) assay in 445 samples (median: eight samples
      per patient) obtained over a median of 40.4 months (95% confidence interval (CI):
      37.0-42.5). The median log HCV-RNA level was 6.77 (95% CI: 6.62-6.92) molecular
      equivalents/mL (MEQ/mL). The median log range of HCV-RNA levels in individual
      patients over the course of the study was 0.89 (95% CI: 0.69-1.16). HCV-RNA level
      varied over time by less than one log in 62% of patients, by 1-1.5 logs in 22%
      and by greater than 1.5 logs in only 17%. Univariate analysis, revealed an
      inverse association between HCV-RNA levels and ALT levels (P=0.037). Univariate
      and logistic regression analysis showed no significant association between HCV
      RNA levels and either the degree of inflammation or fibrosis. In contrast, there
      was a significant positive association between alanine aminotransferase (ALT)
      levels and histological activity especially in individuals with ALTs> 100 IU/L.
      Hence, HCV-RNA levels: (i) almost always fell within the dynamic range of the
      bDNA assay; (ii) were stable in asymptomatic chronically infected patients, with
      only a small proportion of patients exceeding a range of 1.5 logs; (iii) did not
      correlate with either the extent of inflammation or degree of fibrosis. In
      contrast, there was a strong association between ALT level and the histological
      severity of liver disease.

PMID- 11454177
TI  - African Americans with genotype 1 treated with interferon for chronic hepatitis C
      have a lower end of treatment response than Caucasians.
AB  - African Americans as a group have a higher incidence of chronic hepatitis C (CHC)
      than Caucasians but are often under-represented in clinical trials used to define
      response rates to interferon therapy. The aim of this study was to compare
      African Americans with Caucasians with respect to end-of-treatment response to
      interferon. This retrospective study had 61 African Americans and 49 Caucasians
      with CHC. All patients were treated for at least 12 weeks with interferon-alpha2b
      (Intron A) thrice weekly. End-of-treatment response was defined as three
      consecutive nondetectable HCV RNA measurements at least 1 month apart. Sustained
      response was defined as a negative serum HCV RNA 6 months after end of treatment.
      Of the 110 patients, 19 achieved an end-of-treatment response (17%) but only four
      achieved a sustained response (4/110=4%). Of the patients achieving a sustained
      response, one was genotype 1 (male Caucasian), three were genotype 2/3 with four
      patients having no follow-up information. The end-of-treatment response was 7%
      for patients with genotype 1 and 71% for genotype non-1 (P < 0.005 for genotype
      non-1). The end-of-treatment response was significantly higher in Caucasians
      (14/49=31%) compared with African Americans (5/61=8%; P < 0.05). A lower response
      rate in African Americans with genotype 1 in contrast to Caucasians was the
      primary reason for the difference in end-of-treatment response (1/45=2% vs.
      5/33=15%, P < 0.05). Hence, interferon treatment resulted in a poor sustained
      response rate in the group of patients representative of the urban populations
      with the highest prevalence of hepatitis C. A genotype other than type 1 was the
      strongest predictor of end-of-treatment response in patients treated but over 86%
      of patients in this urban clinic were genotype 1. Caucasians were more likely to
      respond than African Americans, especially in patients with genotype 1.

PMID- 11454178
TI  - Two years of lamivudine therapy in anti-HBe-positive patients with chronic
      hepatitis B.
AB  - There is no standard therapy for patients with anti-HBe-positive chronic
      hepatitis B. The aims of this study were to analyse the efficacy of lamivudine
      therapy for two years in these patients and to study the sequence variations in
      the precore and polymerase hepatitis B virus (HBV) regions in relation to
      therapy. Sixteen patients with chronic anti-HBe-positive hepatitis were treated
      with lamivudine (100 mg) once daily for 2 years. Levels of alanine
      aminotransferase (ALT), HBV-DNA and HBsAg were monitored during therapy. The
      polymerase and precore genes were amplified by polymerase chain reaction and
      their products were sequenced directly. Thirteen of 16 patients (81%) had a
      virological and biochemical response after 1 year of therapy and 11 (69%)
      maintained the complete response after 2 years of lamivudine therapy. Among the
      three patients without initial virological or biochemical response at year 1,
      prolonging therapy to 2 years was not associated with an increase in the
      response. YMDD variants were detected in 19% of cases in the first year and in
      44% in the second year: YVDD being the most frequent mutations detected during
      year 1 and YIDD during year 2 of therapy. YMDD variants were found in 7-27% of
      cases with complete response depending on the duration of therapy. Our results
      show that prolonging lamivudine therapy is safe, well tolerated and maintains
      viral inhibition in anti-HBe-positive patients. However, its efficacy tends to
      decrease overtime and it is associated with an increase in YMDD variants, even in
      some cases, of complete response.

PMID- 11454179
TI  - Randomized, placebo-controlled, double-blind trial with interferon-alpha with and
      without amantadine sulphate in primary interferon-alpha nonresponders with
      chronic hepatitis C.
AB  - In primary interferon-alpha (IFN-alpha) nonresponders with chronic hepatitis C,
      retreatment with IFN-alpha has only limited efficacy with sustained response
      rates below 10%. Therefore, the aims of the present study were to compare the
      efficacy and safety of IFN-alpha alone or in combination with amantadine sulphate
      in nonresponders to previous IFN-alpha monotherapy. Fifty-five IFN-alpha
      nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN-alpha
      6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional
      24 weeks. Amantadine sulphate (n=26) or a matched placebo (n=29) was given orally
      twice daily for 48 weeks. Because of a low initial response rate at week 12
      (13/55 patients) and a high breakthrough rate (8/13 patients) after IFN-alpha
      dose reduction in week 24, a virological end-of-treatment response with
      undetectable serum HCV-RNA (< 1000 copies/mL) was achieved in only five patients
      (IFN-alpha/amantadine sulphate, one patient; IFN-alpha/placebo, four patients).
      After 24 weeks follow-up a sustained virological response was observed in only
      two patients receiving IFN-alpha and placebo. Health-related quality-of-life
      analysis showed a substantial improvement of the Profile of Mood States (POMS)
      scale concerning the subscales fatigue (P < 0.05) and vigor (P < 0.05) in
      patients receiving combined IFN-alpha/amantadine sulphate treatment compared with
      those treated with IFN-alpha alone. IFN-alpha/amantadine sulphate combination
      therapy was well tolerated without any serious adverse events. In conclusion,
      retreatment with IFN-alpha and amantadine sulphate does not increase the low
      sustained virological response rates of IFN-alpha therapy in primary IFN-alpha
      nonresponders with chronic hepatitis C, but may lead to a sustained improvement
      of health-related quality-of-life.

PMID- 11454180
TI  - Interferon-alpha plus amantadine in chronic hepatitis C resistant to interferon
      alone: a pilot randomized study.
AB  - The optimal therapy for patients with chronic hepatitis C who have not responded
      to interferon (IFN) is still an unsolved issue. The aim of this study was to
      evaluate the efficacy and tolerability of a high dose of IFN-alpha2a plus
      amantadine for chronic hepatitis C patients who were non-responders to a previous
      course of IFN. Forty consecutive patients with chronic hepatitis C, genotype 1b,
      who had not responded to IFN-alpha, were randomized to receive: (i) IFN 4.5 MU
      daily plus amantadine 200 mg/day for 4 weeks and then IFN 6 MU thrice weekly plus
      amantadine 200 mg/day for an additional 5 months (group A) or (ii) IFN alone at
      the same dosage and duration (group B). After 1 month of therapy, normal alanine
      aminotransferase (ALT) values were observed in three of 21 (14.3%) patients in
      group A and in three of 19 (15.8%) in group B; serum hepatitis C virus (HCV)-RNA
      clearance was observed in one patient (4.8%) in group A and in six (31.6%) in
      group B. At the end of treatment, six patients (28.6%) in group A and three
      (15.8%) in group B had normal ALT levels; however, HCV-RNA in serum was
      detectable in all of them at levels comparable to the basal values; an ALT
      relapse occurred within 3 months of stopping therapy. The combination of daily
      IFN plus amantadine was ineffective in this setting.

PMID- 11454181
TI  - Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection
      -a pilot study.
AB  - Standard treatment for chronic hepatitis C is with interferon (IFN)-alpha and
      ribavirin for 6-12 months. In dialysis patients only interferon therapy is
      currently used due to the lack of knowledge concerning ribavirin dosage and side
      effects. The aim of this study was to investigate if ribavirin can be added to
      interferon when treating dialysis patients with hepatitis C. Five patients on
      haemodialysis and one patient on peritoneal dialysis with chronic hepatitis C,
      five with genotype 1 and one with genotype 4, were given interferon-alpha2b 3 MU
      thrice weekly for 4 weeks, whereafter ribavirin 200-400 mg was added, for an
      intended total treatment period of 28 weeks. Ribavirin plasma concentrations were
      monitored, using HPLC. Four patients completed the treatment. One patient
      suffered marked side-effects from interferon and therapy was terminated. One
      patient developed heart failure and died after 14 weeks of treatment but the
      death was not considered treatment related. Based on plasma concentrations,
      ribavirin doses were frequently adjusted initially. The target concentration (10
      15 micromol/L) was reached with average daily doses of 170-300 mg ribavirin.
      Ribavirin induced anaemia was managed with high doses of erytropoietin (20 000-30
      000 IU/week). Five of six patients became hepatitis C virus (HCV)-RNA negative
      during treatment, but four relapsed post-treatment; one is HCV-RNA negative.
      Hence ribavirin, in combination with IFN-alpha, can be used to treat dialysis
      patients with HCV. However, this requires reduced ribavirin doses and close
      monitoring of ribavirin plasma concentrations and haemoglobin. Ribavirin-induced
      anaemia can be managed with high doses of erythropoeitin.

PMID- 11454182
TI  - Changing epidemiology of hepatitis A and hepatitis E in urban and rural India
      (1982-98).
AB  - The epidemiology of hepatitis A virus (HAV) and hepatitis E virus (HEV) was
      assessed among age-stratified urban high socioeconomic, lower middle
      socioeconomic status and rural populations from western India in 1998. When
      compared with previous surveys, a clear shift from high to intermediate
      endemicity of HAV was evident only for higher socioeconomic population (1982-98),
      raising the possibility of outbreaks of hepatitis A in this category. A decrease
      in anti-HAV positivity was noted in rural children aged 6-10 years. Lower
      circulation of HEV was noted among < 25-year-old urban higher socioeconomic and
      rural individuals. For both viruses, the lower middle socioeconomic populations
      were comparable in 1982 and 1998. Socioeconomic status and family size (odds
      ratio = 23 and 1.6, respectively) were independently associated with anti-HAV
      positivity. Age, lower middle socioeconomic status and well water were
      significant independent variables for HEV infection (odds ratio = 5.7, 2.4 and
      1.9, respectively). Hence, vaccination policy for hepatitis A needs to be
      reviewed.

PMID- 11454183
TI  - Prevalence and genotype distribution of TT virus in various specimen types from
      thalassaemic patients.
AB  - Peripheral blood mononuclear cells (PBMC), plasma, saliva and urine samples were
      collected from 50 thalassaemic patients for TT virus (TTV) detection by two sets
      of PCR. The set B nested PCR was more sensitive than the widely used NG hemi
      nested PCR with TTV positive rates approximately PBMC: 98% vs. 70%; plasma: 92%
      vs. 66%; saliva: 62% vs. 22%; urine: 22% vs. 6%. All 50 patients had TTV detected
      in one or more specimens, with 16% of patients being positive in all four
      specimen types: 40% positive in PBMC, plasma and saliva; 30% positive in PBMC and
      plasma. In 82 NG hemi-nested PCR-positive samples TTV genotype was identified,
      68.3% had a single genotype, 25.6% had multiple genotypes and 6.1% were
      uncharacterized. The positive rates for genotypes by specimen were: G1 (36/82),
      G2 (49/82), G3 (2/82), G4 (7/82), G5 (1/82) and G6 (3/82). Among the 42 patients
      for whom the genotype was examined, 42.9% had single-type infection, 45.2% had co
      infections and 11.9% had uncharacterized genotypes. Sixteen of them had TTV
      detected both in PBMC and plasma with seven having identical genotypes in both
      samples. Eight patients had TTV detected in PBMC, plasma and saliva; two of them
      harboured identical genotypes in all three samples. The results indicate that,
      apart from hepatocytes, PBMC is a major cell type for TTV infection occurs.
      Shedding of TTV in urine and saliva is common and may have a significant role in
      nonblood-borne transmission among the general population. TTV-infected patients
      often harbour multiple genotypes suggesting infection with one genotype does not
      necessarily confer protection against the others. No correlation between TTV
      infection and liver dysfunction was observed.

PMID- 11454184
TI  - Molecular mimicry and autoimmune liver disease: virtuous intentions, malign
      consequences.
AB  - The pathogenesis of autoimmune liver disease and autoimmunity associated with
      chronic viral hepatitis remains poorly understood. One of the major hurdles to a
      deeper understanding of these pathological processes is the absence of clearly
      defined inductive mechanisms, which, if identified and characterised, could guide
      clinical strategies for their prevention or allow therapeutic intervention.
      Molecular mimicry leading to crossreactive autoimmune responses has gained strong
      experimental support in the past decade. A fundamental premise of this hypothesis
      is the involvement of a mimicking environmental trigger. In view of the numerous
      viral and bacterial agents epidemiologically linked to autoimmune liver diseases,
      we and others have proposed molecular mimicry to be an important mechanism in
      these diseases. We also propose similar crossreactive mechanisms to operate in
      the generation of autoimmunity in viral hepatitis. This review focuses on
      molecular mimicry at the level of the B-cell, as few data on T-cell
      crossreactivity in liver disease are thus far available.

PMID- 11454185
TI  - Analysis of haemochromatosis gene mutations in a population from the
      Mediterranean Basin.
AB  - BACKGROUND/AIMS: The C282Y mutation in the haemochromatosis gene (HFE) located on
      chromosome 6 has been identified as the main genetic basis of hereditary
      haemochromatosis (HH). Two more mutations of that gene, H63D and S65C, appear to
      be associated with milder forms of HH. A high allele frequency for C282Y and H63D
      mutations was reported in populations from North Europe, while incomplete
      information is available for individuals from the Mediterranean Basin where C282Y
      homozygotes comprise a smaller percentage of HH cases. In this study we
      investigated the allele frequency of HFE mutations and the association between
      HFE mutations and cases of HH in a population from the South of Italy (Sicily and
      Calabria). In addition, we evaluated a possible association between HFE mutations
      and either chronic liver disease or type II diabetes. PATIENTS AND METHODS: Three
      hundred and twenty-seven individuals (654 chromosomes) were tested for C282Y,
      H63D and S65C mutations of the HFE gene by restriction fragment length
      polymorphism. Four had HH, 23 had hepatocellular carcinoma, 100 had chronic liver
      disease, 100 had type II diabetes, and 100 were healthy controls. RESULTS: Both
      C282Y and S65C mutations were each detected in one of the 654 chromosomes
      analysed (allele frequency=0.15%), while H63D change was found in 122 chromosomes
      (allele frequency=18.6%) and was equally distributed in all the categories
      examined. One healthy individual had compound heterozygosity for C282Y and H63D
      mutations. The frequency of C282Y in this Southern Italian sample was the lowest
      yet reported for a population of European origin. None of the four HH patients
      was either homozygous or heterozygous for C282Y. CONCLUSIONS: In Mediterranean
      populations from Southern Italy the C282Y mutation occurs sporadically and HFE
      polymorphisms seem to have little diagnostic relevance.

PMID- 11454186
TI  - Immunohistochemical analysis of atypical ductular reaction in the human liver,
      with special emphasis on the presence of growth factors and their receptors.
AB  - AIMS/BACKGROUND: The objective of this study was to characterize the expression
      of transforming growth factor-alpha/epidermal growth factor receptor, hepatocyte
      growth factor/c-met, transforming growth factor-beta/Type I-II transforming
      growth factor-beta receptors, stem cell factor, urokinase plasminogen activator,
      smooth muscle actin, CD34 and alpha-fetoprotein in human liver samples with
      (sub)massive necrosis of different etiology containing atypical ductular
      reaction. METHODS: Their presence was studied by immunohistochemistry on paraffin
      embedded tissue sections. RESULTS: Transforming growth factor-alpha and -beta,
      hepatocyte growth factor and their receptors were demonstrated in the ductules;
      additionally stem cell factor and urokinase plasminogen activator were also
      expressed. The atypical ductules were surrounded by smooth muscle actin-positive
      activated stellate cells. CONCLUSION: These phenotypic similarities confirm that
      the atypical ductules in the human liver may be equivalent of oval cells in the
      rat liver, which are regarded as the progeny of stem cells. That is, the atypical
      ductular proliferation may correspond to a stem cell-fed regenerative process.

PMID- 11454187
TI  - Expression of hepatic transporters OATP-C and MRP2 in primary sclerosing
      cholangitis.
AB  - BACKGROUND/AIMS: In chronic cholestatic liver diseases, biliary excretion of
      organic anions from blood into bile is impaired. The aim of this study was to
      identify the underlying mechanism. METHODS: Expression of the basolateral organic
      anion transporting polypeptide OATP-C (SLC21A6) and the canalicular multidrug
      resistance protein 2 (MRP2) was studied in patients with primary sclerosing
      cholangitis (PSC) (n=4), a chronic cholestatic liver disease, and in non
      cholestatic controls (n=4) (two with chronic hepatitis C, one with idiopathic
      liver cirrhosis and one with fatty liver). Total RNA was isolated from liver
      tissue, reverse transcribed and subjected to polymerase chain reaction (PCR)
      amplification using primers specific for OATP-C, MRP2 and beta-actin. PCR
      products were quantified densitometrically. RESULTS: When normalized for beta
      actin expression, the level of OATP-C mRNA in liver tissue of patients with PSC
      was 49% of controls (OATP-C/beta-actin 1.60+/-0.25 vs. 3.24+/-0.69; p<0.05) and
      the level of MRP2 mRNA was 27% of controls (MRP2/beta-actin 0.70+/-0.36 vs.
      2.54+/-0.56; p<0.01). CONCLUSIONS: Both OATP-C and MRP2 are decreased as measured
      by mRNA level in PSC. Downregulation of OATP-C might be the consequence of
      impaired canalicular secretion of organic anions and could serve to reduce the
      organic anion load of cholestatic hepatocytes.

PMID- 11454188
TI  - Clearance of hepatitis B surface antigen in chronic carriers of hepatitis delta
      antibodies.
AB  - BACKGROUND/AIMS: We evaluated the rate of seroclearance of the hepatitis B
      surface antigen (HBsAg) and its clinical significance in patients with chronic
      hepatitis delta virus (HDV). METHODS: Antibody to HDV was tested in HBsAg
      positive subjects admitted to our Hospital from 1991 to 1995. In 1997, a
      biochemical and virologic study was performed in the surviving anti-HD-positive
      patients who had not undergone transplantation. As a control, a cohort of 106
      HBsAg-positive, anti-HD-negative patients was studied. RESULTS: One hundred and
      forty-one subjects were originally positive for anti-HD. After 4 years of follow
      up, six of the 60 patients who underwent re-evaluation (10%) had cleared the
      HBsAg: three of the six patients had minimal changes at the initial liver
      histology and normal ALT, whereas in the remaining three patients with chronic
      active hepatitis ALT normalized during the observation. Anti-HD persisted in five
      of the six patients. Only one patient had raised anti-HBs. In contrast, three of
      106 HBsAg carriers without HDV infection (2.8%) cleared the HBsAg within the same
      time and seroconverted to anti-HBs (p=0.002). CONCLUSION: HBsAg clearance is
      increased over the years in HDV patients compared to ordinary HBsAg carriers, and
      is often associated with improvement of HDV disease without seroconversion to
      anti-HBs.

PMID- 11454189
TI  - Quantitative testing of liver function in relation to fibrosis in patients with
      chronic hepatitis B and C.
AB  - BACKGROUND/AIM: Quantitative tests of liver function may be superior to
      conventional tests to assess the prognosis of patients with liver diseases. There
      are insufficient data from quantitative testing of liver function (QTLF) for
      patients with chronic hepatitis B and C, particularly with regard to fibrosis.
      Therefore, we applied a broad panel of QTLF to these patients. METHODS: Three
      hundred and sixty-seven consecutive patients with chronic hepatitis B or C
      underwent liver biopsy and QTLF, which included tests for hepatic metabolism
      (aminopyrine breath test, galactose elimination capacity) and for hepatic
      perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were
      correlated with liver histology (grading and staging for inflammation and
      fibrosis) and Child-Pugh classification for liver cirrhosis. RESULTS: In patients
      with no and moderate fibrosis, metabolic liver function was significantly
      decreased, whereas hepatic perfusion remained normal. Severe fibrosis and
      cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only
      reduced metabolic liver function, irrespective of the inflammatory grade. Viral
      etiology and HCV genotypes did not change QTLF. CONCLUSIONS: In summary, viral
      damage compromises hepatic metabolism before perfusion. Therefore, tests of
      metabolic liver function (aminopyrine breath test, galactose elimination
      capacity) should be useful to search for drugs that restore liver function in
      viral hepatitis irrespective of the fibrosis stage.

PMID- 11454190
TI  - Chronic hepatitis C and superimposed nonalcoholic fatty liver disease.
AB  - BACKGROUND/AIMS: Hepatitis C and nonalcoholic fatty liver disease (NAFL) are the
      two most common forms of liver disease in the United States. Recently, obesity
      and its associated risk factors have been suggested to enhance HCV-related
      fibrosis. The aim of this study was to assess the impact of hepatic steatosis,
      steatohepatitis, and its associated risk factors on HCV-related fibrosis.
      METHODS: Patients with untreated, biopsy-proven, chronic hepatitis C (6/97-3/99)
      were included. Clinical and demographic data at the time of liver biopsy were
      obtained from chart review and verified by telephone survey. One
      hepatopathologist reviewed all pathologic specimens, using the modified
      histological activity index score and the Ishak staging for fibrosis and a NAFL
      pathologic protocol. RESULTS: One hundred and seventy patients with hepatitis C
      were included [age: 48.7+/-9.33 (years), body mass index (BMI): 28.1+/-5.7
      (kg/m2) and type 2 diabetes mellitus (DM): 14%]. Of these, 77 (45.3%) had no or
      mild fibrosis and 93 (54.7%) had advanced fibrosis. Hepatic steatosis was seen in
      90 (52.9%) patients. The grade of steatosis was associated with markers of
      obesity only. Age (p=0.002), type 2 DM (p=0.04), and superimposed steatohepatitis
      (p=0.047) were independently associated with advanced fibrosis. Superimposed
      nonalcoholic steatohepatitis (NASH) was seen in 17 (10%) patients. Patients with
      superimposed NASH were mostly obese (76.5%), males (62%) with 16% having type 2
      diabetes and a BMI 33.8+/-7.12. CONCLUSION: In patients with chronic hepatitis C,
      type 2 DM and superimposed steatohepatitis are independently associated with
      advanced fibrosis.

PMID- 11454191
TI  - Apoptotic pathways in primary biliary cirrhosis and autoimmune hepatitis.
AB  - BACKGROUND/AIMS: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC)
      are two autoimmune diseases with unknown etiologies that primarily target the
      liver. In both diseases, liver lesions are accompanied by large infiltrates of
      mononuclear cells. The purpose of this study was to determine if either the Fas
      mediated or the granule-exocytosis pathways contribute to apoptosis in these
      diseases. METHODS: To determine the involvement of apoptosis in tissue injury we
      examined liver tissue for DNA fragmentation and morphological characteristics of
      apoptosis. The major cytotoxic pathways of activated lymphocytes were compared by
      quantitating the levels of transcripts for FasL and granzyme B, and expression
      was confirmed by immunoprecipitation of these molecules. RESULTS: In both
      diseases, apoptosis was observed. However, the main cell types undergoing
      apoptosis were hepatocytes in AIH, and biliary epithelial cells in PBC. In AIH
      the levels of FasL and granzyme B mRNA were increased over the levels detected in
      normal liver, while in PBC only the levels of granzyme B were elevated.
      Additionally, in AIH, the ratio of FasL transcripts to granzyme B transcripts was
      elevated, reflecting a possible increase in the relative contribution of FasL to
      the progression of the disease. Immunoprecipitation studies further support an
      increase in FasL protein expression in AIH. CONCLUSIONS: These data suggest that
      both FasL and granzyme B contribute to the apoptosis observed in AIH and PBC.
      However, FasL appears to play a more prominent role in the induction of
      hepatocyte apoptosis and tissue destruction in AIH.

PMID- 11454192
TI  - Chinese medicinal herbs for chronic hepatitis B: a systematic review.
AB  - AIMS/BACKGROUND: Chronic hepatitis B is a serious health problem worldwide.
      Chinese medicinal herbs are widely used for treatment of chronic hepatitis B in
      China and many clinical trials have been conducted. This systematic review is to
      assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis
      B. METHODS: Randomised clinical trials comparing Chinese medicinal herbs versus
      placebo, no intervention, nonspecific treatment, or interferon treatment for
      chronic hepatitis B with > or = 3 months follow-up were included. No language and
      blinding limitations were applied. The electronic databases were searched,
      combined with handsearches on Chinese literature. Data were extracted
      independently by two reviewers. The methodological quality of trials was assessed
      by the Jadad-scale plus allocation concealment. RESULTS: Nine randomised trials
      (n=936) were included, with only one being of high quality. There was a funnel
      plot asymmetry (intercept 3.37, p=0.047). Compared to nonspecific treatment or
      placebo, the herbal compound Fuzheng Jiedu Tang showed an effect on clearance of
      serum HBsAg (relative risk 5.19, 95% CI 1.24-21.79), HBeAg (10.85, 3.56-33.06),
      and HBV DNA (8.50, 1.23-58.85). Polyporus umbellatus polysaccharide showed an
      effect on serum HBeAg (3.06, 1.13-8.29) and HBV DNA (4.14, 1.0-17.19);
      Phyllanthus amarus showed an effect on serum HBeAg (3.35, 1.49-7.56). Phyllanthus
      compound and kurorinone showed no significant difference on clearance of serum
      HBeAg and HBV DNA and on alanine aminotransferase normalisation compared to
      interferon. No serious adverse event was observed. CONCLUSIONS: Chinese medicinal
      herbs are not recommended for chronic hepatitis B because of the publication bias
      and low quality of the trials. Rigorously designed, randomised, double-blind,
      placebo-controlled trials are needed.

PMID- 11454193
TI  - Acute liver failure as the initial manifestation of acute leukaemia.
AB  - BACKGROUND/AIMS: Haematological malignancies seldom cause clinically significant
      liver disease. Acute liver failure as the initial manifestation of acute
      leukaemia is very rare and carries a very poor prognosis. METHODS/RESULTS: Three
      cases of acute liver failure secondary to acute leukaemia are described. Each
      case presented initially as acute liver failure of uncertain cause. Specific
      treatment for the leukaemia was instituted; however, all three patients died as a
      consequence of the liver failure. We describe the clinical course and relevant
      investigations of these patients and discuss possible mechanisms of acute liver
      failure in this setting. CONCLUSION: Acute leukaemia presenting as acute liver
      failure has a very poor prognosis. Although a rare cause of acute liver failure,
      it should be considered in any patient presenting with acute liver failure with
      prodromal symptoms and a raised peripheral white cell count, lactate
      dehydrogenase and uric acid.

PMID- 11454194
TI  - Can hepatic stellate cells express alpha-smooth muscle actin in normal human
      liver?

PMID- 11454195
TI  - Mediator--a universal complex in transcriptional regulation.
AB  - The Mediator complex is essential for basal and regulated expression of nearly
      all RNA polymerase II-dependent genes in the Saccharomyces cerevisiae genome.
      Mediator acts as a bridge, conveying regulatory information from enhancers and
      other control elements to the promoter. It is now clear that Mediator-like
      complexes also exist in higher eukaryotic cells and that they have an important
      role in metazoan transcriptional regulation. However, the exact mechanism of
      Mediator-dependent transcriptional regulation remains unclear. We review here
      some recent advances in our understanding of Mediator structure and function. We
      also discuss a model to account for the functional and evolutionary relationship
      between yeast and metazoan Mediators. As an appendix to this review, we have
      created a database, MEDB, in which we have compiled information about all the S.
      cerevisiae Mediator subunits and their homologues in other eukaryotic cells
      (http://bio.lundberg.gu.se/medb/).

PMID- 11454196
TI  - Feedback controls restrain the initiation of Escherichia coli chromosomal
      replication.
AB  - In Escherichia coli, initiation of chromosomal replication is activated by a
      nucleoprotein complex formed primarily between the DnaA protein and oriC
      (replication origin) DNA. After replicational initiation, this complex has to be
      inactivated in order to repress the appearance of initiation events until the
      next scheduled round of initiation. Studies of the mechanisms responsible for
      this repression have recently revealed direct coupling between these mechanisms
      and key elements of the replication process, suggesting that feedback-type
      regulatory loops exist between the factors implicated in initiation and the
      elements yielded by the replication process. The loading of the ring-shaped beta
      subunit of DNA polymerase III onto DNA plays a key role in the inactivation of
      the DnaA protein. Duplication of oriC DNA results in hemimethylated DNA, which is
      inert for reinitiation. Titration of large amounts of DnaA protein to a non-oriC
      locus can repress untimely initiations, and timely duplication of this locus is
      required for this repression in rapidly growing cells. All these systems
      functionally complement one another to ensure the maintenance of the
      interinitiation interval between two normal DNA replication cycles. The
      mechanisms that link the replication cycle to the progression of the cell cycle
      are also discussed.

PMID- 11454197
TI  - The germ tubes of Candida albicans hyphae and pseudohyphae show different
      patterns of septin ring localization.
AB  - The location of the septin ring in the germ tubes of Candida albicans hyphae and
      pseudohyphae was studied using an antibody to Saccharomyces cerevisiae Cdc11p. In
      pseudohyphae induced by growth at 35 degrees C in YEPD or Lee's medium, a septin
      ring formed at or near (mean 1.8 microm) the neck between the mother cell and the
      germ tube. This became double later in the cycle, and the first mitosis took
      place across the plane of this double ring. A septin ring also formed at the germ
      tube neck of developing hyphae induced by serum or growth on Lee's medium at 37
      degrees C. However, at later times, this ring became disorganized and
      disappeared. A second double ring then appeared 10-15 microm (mean 12.5 microm)
      along the length of the germ tube. The nucleus subsequently migrated out of the
      mother cell into the germ tube, and the first mitosis took place across the plane
      of this second septin ring. The relocation of the septin ring in developing
      hyphae provides a clear-cut molecular distinction between hyphae and
      pseudohyphae. Commitment to one type of septin localization and mitosis was shown
      to occur early in the first mitotic cycle, well before evagination. Germ tubes of
      hyphae and pseudohyphae also have different widths. A point of commitment to germ
      tube width was also demonstrated, but occurred later in the cycle, approximately
      coincident with the time of evagination.

PMID- 11454198
TI  - Deletion of a novel protein kinase with PX and FYVE-related domains increases the
      rate of differentiation of Trypanosoma brucei.
AB  - Growth control of African trypanosomes in the mammalian host is coupled to
      differentiation of a non-dividing life cycle stage, the stumpy bloodstream form.
      We show that a protein kinase with novel domain architecture is important for
      growth regulation. Zinc finger kinase (ZFK) has a kinase domain related to RAC
      and S6 kinases flanked by a FYVE-related zinc finger and a phox (PX) homology
      domain. To investigate the function of the kinase during cyclical development, a
      stable transformation procedure for bloodstream forms of differentiation
      competent (pleomorphic) Trypanosoma brucei strains was established. Deletion of
      both allelic copies of ZFK by homologous recombination resulted in reduced growth
      of bloodstream-form parasites in culture, which was correlated with an increased
      rate of differentiation to the non-dividing stumpy form. Growth and
      differentiation rates were returned to wild-type level by ectopic ZFK expression.
      The phenotype is stage-specific, as growth of procyclic (insect form)
      trypanosomes was unaffected, and Deltazfk/Deltazfk clones were able to undergo
      full cyclical development in the tsetse fly vector. Deletion of ZFK in a
      differentiation-defective (monomorphic) strain of T. brucei did not change its
      growth rate in the bloodstream stage. This suggests a function of ZFK associated
      with the trypanosomes' decision between either cell cycle progression, as slender
      bloodstream form, or differentiation to the non-dividing stumpy form.

PMID- 11454199
TI  - A novel ligand from Plasmodium falciparum that binds to a sialic acid-containing
      receptor on the surface of human erythrocytes.
AB  - Invasion of the merozoite form of Plasmodium falciparum into human erythrocytes
      involves multiple receptor-ligand interactions. The EBA175 protein of P.
      falciparum has been shown to be the ligand that binds to a sialic acid-dependent
      site on glycophorin A. We have identified a novel P. falciparum ligand, termed
      erythrocyte-binding antigen 140 (EBA140), that shares structural features and
      homology with EBA175. Subcellular localization of EBA140 suggests that it is
      located in the micronemes, the same localization as EBA175. EBA140 binds to a
      sialic acid-dependent receptor on the surface of human erythrocytes. Binding of
      EBA140 to this erythrocyte receptor is sensitive to neuraminidase and resistant
      to trypsin, proteinase K and pronase. The protease-resistant properties of the
      erythrocyte receptor suggests that it is not glycophorin A or C. Additionally,
      analysis of mutant erythrocytes from humans has shown that EBA140 does not bind
      glycophorin B. Interestingly, we have identified a parasite line that lacks the
      eba140 gene, suggesting that this protein is not essential for in vitro invasion.
      These results suggest that EBA140 may be involved in merozoite invasion using a
      sialic acid-dependent receptor on human erythrocytes.

PMID- 11454200
TI  - Alkaline shock induces the Bacillus subtilis sigma(W) regulon.
AB  - When confronted with a stress factor, bacteria react with a specific stress
      response, a genetically encoded programme resulting in the transiently enhanced
      expression of a subset of genes. One of these stress factors is a sudden increase
      in the external pH. As a first step to understand the response of Bacillus
      subtilis cells towards an alkali shock at the transcriptional level, we attempted
      to identify alkali-inducible genes using the DNA macroarray technique. To define
      the appropriate challenging conditions, we used the ydjF gene, the orthologue of
      the Escherichia coli pspA, as a model gene for an alkali-inducible gene.
      Hybridization of 33P-labelled cDNA to a DNA macroarray revealed induction of more
      than 80 genes by a sudden increase in the external pH value from 6.3 to 8.9. It
      was discovered that a large subset of these genes belong to the recently
      described sigmaW regulon, which was confirmed by the analysis of a sigW knockout.
      A comparison of B. subtilis wild type with the congenic sigW knockout also led to
      the discovery of new members of the sigmaW regulon. In addition, we found several
      genes clearly not belonging to that regulon. This analysis represents the first
      report of an extracellular stimulus inducing the sigmaW regulon.

PMID- 11454201
TI  - The ratio between CcdA and CcdB modulates the transcriptional repression of the
      ccd poison-antidote system.
AB  - The ccd operon of the F plasmid encodes CcdB, a toxin targeting the essential
      gyrase of Escherichia coli, and CcdA, the unstable antidote that interacts with
      CcdB to neutralize its toxicity. Although work from our group and others has
      established that CcdA and CcdB are required for transcriptional repression of the
      operon, the underlying mechanism remains unclear. The results presented here
      indicate that, although CcdA is the DNA-binding element of the CcdA-CcdB complex,
      the stoichiometry of the two proteins determines whether or not the complex binds
      to the ccd operator-promoter region. Using electrophoretic mobility shift assays,
      we show that a (CcdA)2-(CcdB)2 complex binds DNA. The addition of extra CcdB to
      that protein-DNA complex completely abolishes DNA retardation. Based on these
      results, we propose a model in which the ratio between CcdA and CcdB regulates
      the repression state of the ccd operon. When the level of CcdA is superior or
      equal to that of CcdB, repression results. In contrast, derepression occurs when
      CcdB is in excess of CcdA. By ensuring an antidote-toxin ratio greater than one,
      this mechanism could prevent the harmful effect of CcdB in plasmid-containing
      bacteria.

PMID- 11454202
TI  - Escherichia coli FtsZ polymers contain mostly GTP and have a high nucleotide
      turnover.
AB  - The cell division protein FtsZ is a GTPase structurally related to tubulin and,
      like tubulin, it assembles in vitro into filaments, sheets and other structures.
      To study the roles that GTP binding and hydrolysis play in the dynamics of FtsZ
      polymerization, the nucleotide contents of FtsZ were measured under different
      polymerizing conditions using a nitrocellulose filter-binding assay, whereas
      polymerization of the protein was followed in parallel by light scattering.
      Unpolymerized FtsZ bound 1 mol of GTP mol(-1) protein monomer. At pH 7.5 and in
      the presence of Mg(2+) and K(+), there was a strong GTPase activity; most of the
      bound nucleotide was GTP during the first few minutes but, later, the amount of
      GTP decreased in parallel with depolymerization, whereas the total nucleotide
      contents remained invariant. These results show that the long FtsZ polymers
      formed in solution contain mostly GTP. Incorporation of nucleotides into the
      protein was very fast either when the label was introduced at the onset of the
      reaction or subsequently during polymerization. Molecular modelling of an FtsZ
      dimer showed the presence of a cleft between the two subunits maintaining the
      nucleotide binding site open to the medium. These results show that the FtsZ
      polymers are highly dynamic structures that quickly exchange the bound
      nucleotide, and this exchange can occur in all the subunits.

PMID- 11454203
TI  - Inactivation of a gene that is highly conserved in Gram-positive bacteria
      stimulates degradation of non-native proteins and concomitantly increases stress
      tolerance in Lactococcus lactis.
AB  - Exposure of cells to elevated temperatures triggers the synthesis of chaperones
      and proteases including components of the conserved Clp protease complex. We
      demonstrated previously that the proteolytic subunit, ClpP, plays a major role in
      stress tolerance and in the degradation of non-native proteins in the Gram
      positive bacterium Lactococcus lactis. Here, we used transposon mutagenesis to
      generate mutants in which the temperature- and puromycin-sensitive phenotype of a
      lactococcal clpP null mutant was partly alleviated. In all mutants obtained, the
      transposon was inserted in the L. lactis trmA gene. When analysing a clpP, trmA
      double mutant, we found that the expression normally induced from the clpP and
      dnaK promoters in the clpP mutant was reduced to wild-type level upon
      introduction of the trmA disruption. Additionally, the degradation of puromycyl
      containing polypeptides was increased, suggesting that inactivation of trmA
      compensates for the absence of ClpP by stimulating an as yet unidentified
      protease that degrades misfolded proteins. When trmA was disrupted in wild-type
      cells, both stress tolerance and proteolysis of puromycyl peptides was enhanced
      above wild-type level. Based on our results, we propose that TrmA, which is well
      conserved in several Gram-positive bacteria, affects the degradation of non
      native proteins and thereby controls stress tolerance.

PMID- 11454204
TI  - Spatial and temporal sequence of capsule construction in Cryptococcus neoformans.
AB  - The pathogenic yeast Cryptococcus neoformans is distinguished by an extensive
      polysaccharide capsule, which impedes host defences and is absolutely required
      for fungal virulence. Despite the biological importance of the capsule, nothing
      is known about how it is assembled. Substantial capsule growth occurs in two
      distinct situations relevant to cryptococcal pathogenesis: formation of new buds
      and induction of capsule on mature cells. We developed pulse-chase protocols to
      examine these events in a dynamic way using a variety of microscopy techniques.
      We show that the capsule overlying buds is newly synthesized and differs
      physically from the corresponding parental material. New capsule formed by mature
      cells upon induction of synthesis is added at the inner aspect of the existing
      structure, displacing pre-existing material outwards. Surprisingly, new
      polysaccharide material is also deposited throughout the capsule, yielding a
      progressively denser structure. These results yield the first model of capsule
      synthesis and open new lines of investigation into the underlying mechanisms.

PMID- 11454205
TI  - Regulation of late flagellar gene transcription and cell division by flagellum
      assembly in Caulobacter crescentus.
AB  - Biogenesis of the single polar flagellum of Caulobacter crescentus is regulated
      by a complex interplay of cell cycle events and the progression of flagellum
      assembly. The expression of class III/IV flagellar genes requires the assembly of
      an early flagellar basal body structure, encoded by class II genes, and is
      activated by the transcription factor FlbD. Previous experiments indicated that
      the class II flagellar gene, flbE, encoded a trans-acting factor that was
      required for FlbD activity. Here, using mutant alleles of flbE we have determined
      that FlbE is either a structural component of the flagellum or is required for
      flagellar assembly and does not, as originally proposed, function as a trans
      acting factor. We also demonstrate that two deleted derivatives of flbE have a
      dominant negative effect on the transcriptional activation of class III/IV
      flagellar genes that can be relieved by a gain-of-function mutation in flbD
      called bfa. This same mutation in flbD has been shown to restore class III/IV
      transcription in the absence of early class II flagellar assembly. These deleted
      mutants of flbE also exhibited a filamentous cell phenotype that was
      indistinguishable from that previously observed in class II flagellar mutants.
      Introduction of a flbD-bfa mutation into these cells expressing the deleted
      alleles of flbE, as well as several class II mutant strains, restored normal cell
      division and FtsZ localization. These results suggest that class III/IV
      transcription and a step in cell division are coupled to flagellar assembly by
      the same genetic pathway.

PMID- 11454206
TI  - Exploring the minimal substrate requirements for trans-cleavage by RNase P
      holoenzymes from Escherichia coli and Bacillus subtilis.
AB  - We analysed the processing of small bipartite model substrates by Escherichia
      coli and Bacillus subtilis RNase P and corresponding hybrid enzymes. We
      demonstrate specific trans-cleavage of a model substrate with a 4 bp stem and a 1
      nucleotide (nt) 5' flank, representing to date the smallest mimic of a natural
      RNase P substrate that could be processed in trans at the canonical RNase P
      cleavage site. Processing efficiencies decreased up to 5000-fold when the 5'
      flank was shortened from 3 to 1 nt. Reduction of the 5' flank to 1 nt was more
      deleterious than reducing the stem from 7 to 4 bp, although the 4 bp duplex
      formed only transiently, in contrast to the stable 7 bp duplex. These results
      indicate that the crucial contribution of nt -2 in the single-stranded 5' flank
      to productive interaction is a general feature of A- and B-type bacterial RNase P
      enzymes. We also showed that an Rp-phosphorothioate modification at nt -2
      interferes with processing. Bacterial RNase P holoenzymes are also capable of
      cleaving single-stranded RNA oligonucleotides as short as 5 nt, yielding RNase P
      specific 5'-phosphate and 3'-OH termini, with measured turnover rates of up to
      0.7 min-1. All cleavage sites were at least 2 nt away from the 5' and 3' ends of
      the oligonucleotides. Some cleavage site preferences were observed dependent on
      the identity of the RNase P RNA subunit.

PMID- 11454207
TI  - Gelatinase biosynthesis-activating pheromone: a peptide lactone that mediates a
      quorum sensing in Enterococcus faecalis.
AB  - Biosynthesis of gelatinase, a virulence factor of Enterococcus faecalis, was
      found to be regulated in a cell density-dependent fashion in which its production
      is active in late log to early stationary phase. Addition of early stationary
      phase culture filtrate to medium shifted the onset of gelatinase production to
      that of mid-log phase, suggesting that E. faecalis secretes a gelatinase
      biosynthesis-activating pheromone (GBAP). GBAP was isolated from culture
      supernatant of E. faecalis OG1S-P. Structural analysis suggested GBAP to be an 11
      residue cyclic peptide containing a lactone structure, in which the alpha
      carboxyl group of the C-terminal amino acid is linked to a hydroxyl group of the
      serine of the third residue. A synthetic peptide possessing the deduced structure
      showed GBAP activity at nanomolar concentrations as did natural GBAP. Database
      searches revealed that GBAP corresponds to a C-terminal part of a 242-residue
      FsrB protein. Northern analysis showed that GBAP slowly induces the transcription
      of two operons, fsrB-fsrC encoding FsrB and a putative histidine kinase FsrC and
      gelE-sprE encoding gelatinase GelE and serine protease SprE. Strains with an
      insertion mutation in either fsrC or a putative response regulator gene fsrA
      failed to respond to GBAP, suggesting that the GBAP signal is transduced by a two
      component regulatory system.

PMID- 11454208
TI  - The negative regulator Opi1 of phospholipid biosynthesis in yeast contacts the
      pleiotropic repressor Sin3 and the transcriptional activator Ino2.
AB  - Structural genes of phospholipid biosynthesis in the yeast Saccharomyces
      cerevisiae are transcriptionally co-regulated by ICRE (inositol/choline
      responsive element) promoter motifs. Gene activation by an ICRE is mediated by
      binding of the Ino2/Ino4 transcription factor, whereas repression in the presence
      of high concentrations of inositol and choline (IC) requires an intact Opi1
      repressor. However, the mechanism of specific repression and the functional
      interplay among these regulators remained unclear from previous work. Using in
      vivo as well as in vitro interaction assays, we show binding of the pleiotropic
      repressor Sin3 to the pathway-specific regulator Opi1. The paired amphipathic
      helix 1 (PAH1) within Sin3 and OSID (Opi1-Sin3 interaction domain) in the N
      terminus of Opi1 were mapped as contact sites. The regulatory significance of the
      Opi1-Sin3 interaction was shown by the obvious deregulation of an ICRE-dependent
      reporter gene in a sin3 mutant. Opi1 also interacts with a newly identified
      functional domain of the transcriptional activator Ino2 (RID, repressor
      interaction domain). These results define the molecular composition of the
      transcription complex mediating control of ICRE-dependent genes and allow a
      hypothesis on the flow of regulatory information in response to phospholipid
      precursors.

PMID- 11454209
TI  - Involvement of N-acetylmuramyl-L-alanine amidases in cell separation and
      antibiotic-induced autolysis of Escherichia coli.
AB  - N-acetylmuramyl-L-alanine amidases are widely distributed among bacteria.
      However, in Escherichia coli, only one periplasmic amidase has been described
      until now, which is suggested to play a role in murein recycling. Here, we report
      that three amidases, named AmiA, B and C, exist in E. coli and that they are
      involved in splitting of the murein septum during cell division. Moreover, the
      amidases were shown to act as powerful autolytic enzymes in the presence of
      antibiotics. Deletion mutants in amiA, B and C were growing in long chains of
      unseparated cells and displayed a tolerant response to the normally lytic
      combination of aztreonam and bulgecin. Isolated murein sacculi of these chain
      forming mutants showed rings of thickened murein at the site of blocked
      septation. In vitro, these murein ring structures were digested more slowly by
      muramidases than the surrounding murein. In contrast, when treated with the
      amidase AmiC or the endopeptidase MepA, the rings disappeared, and gaps developed
      at these sites in the murein sacculi. These results are taken as evidence that
      highly stressed murein cross-bridges are concentrated at the site of blocked cell
      division, which, when cleaved, result in cracking of the sacculus at this site.
      As amidase deletion mutants accumulate trimeric and tetrameric cross-links in
      their murein, it is suggested that these structures mark the division site before
      cleavage of the septum.

PMID- 11454210
TI  - An essential role for phoP in Mycobacterium tuberculosis virulence.
AB  - Two-component regulatory proteins function in bacteria as sensory and adaptive
      factors in response to a wide range of environmental stimuli. Some two-component
      systems, such as PhoP/PhoQ, control transcription of key virulence genes
      essential for survival in host cells in diverse intracellular bacterial
      pathogens, including Salmonella sp., Shigella sp. and Yersinia sp. In this study,
      we have disrupted the phoP gene from Mycobacterium tuberculosis, which codes for
      a putative transcription regulator factor of the two-component system PhoP/PhoR.
      The phoP mutant strain exhibited impaired multiplication when cultured in mouse
      bone marrow-derived macrophages. However, the mutation did not appear to affect
      survival of the organisms adversely inside macrophages. The mutant strain was
      also attenuated in vivo in a mouse infection model, with impaired growth observed
      in the lungs, livers and spleens. The results suggest that the phoP gene is
      required for intracellular growth of M. tuberculosis but is not essential for
      persistence of the bacilli.

PMID- 11454211
TI  - A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a
      structural modification of the major porin.
AB  - In Enterobacter aerogenes, multidrug resistance involves a decrease in outer
      membrane permeability associated with changes in an as yet uncharacterized porin.
      We purified the major porin from the wild-type strain and a resistant strain. We
      characterized this porin, which was found to be an OmpC/OmpF-like protein and
      analysed its pore-forming properties in lipid bilayers. The porin from the
      resistant strain was compared with the wild-type protein and we observed (i) that
      its single-channel conductance was 70% lower than that of the wild type; (ii)
      that it was three times more selective for cations; (iii) a lack of voltage
      sensitivity. These results indicate that the clinical strain is able to
      synthesize a modified porin that decreases the permeability of the outer
      membrane. Mass spectrometry experiments identified a G to D mutation in the
      putative loop 3 of the porin. Given the known importance of this loop in
      determining the pore properties of porins, we suggest that this mutation is
      responsible for the novel resistance mechanism developed by this clinical strain,
      with changes in porin channel function acting as a new bacterial strategy for
      controlling beta-lactam diffusion via porins.

PMID- 11454212
TI  - Cloning of the genes for a 4-sulphocatechol-oxidizing protocatechuate 3,4
      dioxygenase from Hydrogenophaga intermedia S1 and identification of the amino
      acid residues responsible for the ability to convert 4-sulphocatechol.
AB  - The genes for a protocatechuate 3,4-dioxygenase (P34O-II) with the ability to
      oxidize 4-sulphocatechol were cloned from the 4
      aminobenzenesulphonate(sulphanilate)-degrading bacterium Hydrogenophaga
      intermedia strain S1 (DSMZ 5680). Sequence comparisons of the deduced amino acid
      sequences of both subunits of the P34O-II from H. intermedia S1 (PcaH-II and PcaG
      II) with those of another P34O-II, previously obtained from Agrobacterium
      radiobacter S2, and the corresponding sequences from the protocatechuate 3,4
      dioxygenases from other bacterial genera demonstrated that seven amino acid
      residues, which were conserved in all previously known P34Os (P34O-Is), were
      different in both P34O-IIs. According to previously published structural data for
      the P34O of Pseudomonas putida only two of these amino acid residues were located
      near the catalytical centre. The respective amino acid residues were mutated in
      the P34O-I from A. radiobacter S2 by site-specific mutagenesis, and it was found
      that a single amino acid exchange enabled the protocatechuate converting P34O
      also to oxidize 4-sulphocatechol.

PMID- 11454213
TI  - Codon-usage based regulation of colicin K synthesis by the stress alarmone ppGpp.
AB  - The molecular mechanism of the upregulation of Escherichia coli colicin K (Cka)
      synthesis during stress conditions was studied. Nutrient starvation experiments
      and the use of relA spoT mutant strains, IPTG-regulated overproduction of ppGpp
      and lacZ fusions revealed that the stringent response alarmone guanosine 3',5'
      bispyrophosphate (ppGpp) is the main positive effector of Cka synthesis.
      Comparison of the amounts of protein produced (Western blotting) and specific
      mRNA (Northern blotting) before and after nutrient starvation demonstrated
      increases in Cka protein with unaltered specific mRNA levels, suggesting a post
      transcriptional regulatory mechanism. Reporter (beta-galactosidase) assays using
      truncated cka of variable length fused to lacZ located the key regulatory region
      close to the 5' end of the cka mRNA. Closer analysis of this region indicated the
      presence of several rare codons, including the leucine-encoding codon CUA.
      Synonymous exchange of the rare codons with more frequently used ones abolished
      the regulatory effect of ppGpp. Supplementation of the strain with the plasmid
      CodonPlus carrying several rare tRNA genes yielded similar results, indicating
      that codon usage (in particular, the fifth codon for the amino acid leucine) and
      tRNA availability (i.e. tRNAleu) are the key elements of the regulatory function
      of ppGpp. We conclude that ppGpp regulates Cka synthesis via a novel post
      transcriptional mechanism that is based on rare codon usage and variable cognate
      tRNA availability.

PMID- 11454214
TI  - The genetic organization of Desulfovibrio desulphuricans ATCC 27774
      bacterioferritin and rubredoxin-2 genes: involvement of rubredoxin in iron
      metabolism.
AB  - The anaerobic bacterium Desulfovibrio desulphuricans ATCC 27774 contains a unique
      bacterioferritin, isolated with a stable di-iron centre and having iron
      coproporphyrin III as its haem cofactor, as well as a type 2 rubredoxin with an
      unusual spacing of four amino acid residues between the first two binding
      cysteines. The genes encoding for these two proteins were cloned and sequenced.
      The deduced amino acid sequence of the bacterioferritin shows that it is among
      the most divergent members of this protein family. Most interestingly, the
      bacterioferritin and rubredoxin-2 genes form a dicistronic operon, which reflects
      the direct interaction between the two proteins. Indeed, bacterioferritin and
      rubredoxin-2 form a complex in vitro, as shown by the significant increase in the
      anisotropy and decay times of the fluorescence of rubredoxin-2 tryptophan(s) when
      mixed with bacterioferritin. In addition, rubredoxin-2 donates electrons to
      bacterioferritin. This is the first identification of an electron donor to a
      bacterioferritin and shows the involvement of rubredoxin-2 in iron metabolism.
      Furthermore, analysis of the genomic data for anaerobes suggests that rubredoxins
      play a general role in iron metabolism and oxygen detoxification in these
      prokaryotes.

PMID- 11454215
TI  - Increased expression of Borrelia burgdorferi vlsE in response to human
      endothelial cell membranes.
AB  - RNA isolated from virulent Borrelia burgdorferi cells incubated with human
      endothelial or neurological tissue cells was subjected to subtractive
      hybridization using RNA from the same strain incubated in tissue culture medium
      alone. This RNA subtractive technique generated specific probes that hybridized
      to two restriction fragments (8.2 kb and 10 kb respectively) generated by EcoRI
      digestion of total plasmid DNA. The 10 kb EcoRI fragment localized to lp28-1 and
      was subsequently identified as the variable membrane protein-like sequence (vls)
      region, which includes an expression locus (vlsE) and 15 silent cassettes. vlsE
      encodes a 36 kDa outer surface protein that undergoes antigenic variation during
      animal infections. Primer extension analysis identified the 5' end of a
      transcript and a putative promoter for vlsE. Quantitative reverse transcription
      polymerase chain reaction (RT-PCR) suggested that the expression of vlsE
      increased when virulent B. burgdorferi cells were incubated with human tissue
      cells or purified cell membranes isolated from those same cell lines. A 138 bp
      region upstream of the vlsE region that was not reported in the genome sequence
      was sequenced using specific 32P end-labelled primers in a DNA cycle sequencing
      system at high annealing temperatures. Analysis revealed that it contained a 51
      bp inverted repeat, which could form an extremely stable cruciform structure.
      Southern blots probed with the vlsE promoter/operator region indicated that part
      or all of this sequence could be found on other B. burgdorferi plasmids.

PMID- 11454216
TI  - Transport of cytochrome c derivatives by the bacterial Tat protein translocation
      system.
AB  - An experimental system developed previously for the heterologous expression of c
      type cytochromes in Escherichia coli Q1has been adapted to monitor protein
      transfer across the bacteria's cytoplasmic membrane. Apocytochrome, lacking the
      haem cofactor and probably in an unfolded state, was readily transferred across
      the cytoplasmic membrane when fused to a Sec-specific signal peptide.
      Furthermore, cytochrome fused to a signal peptide regarded as specific for the
      twin arginine transport (Tat) system was translocated in an unfolded state by the
      Sec apparatus. After maturation and folding in the cytoplasm, Tat-mediated
      transfer of holocytochrome to the periplasm occurred. We conclude that, in
      addition to the nature of the specific signal peptide, the folding state of a
      particular protein also governs its acceptance by a given transport system.

PMID- 11454217
TI  - The two-component system ArlS-ArlR is a regulator of virulence gene expression in
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a major human pathogen that produces many virulence
      factors in a temporally regulated manner controlled by at least two global
      virulence regulatory loci (agr and sarA). We identified previously a two
      component system, ArlS-ArlR, that modifies the activity of extracellular serine
      protease and may be involved in virulence regulation. Here, we show that
      mutations in either arlR or arlS increase the production of secreted proteins
      [alpha-toxin (Hla), beta-haemolysin, lipase, coagulase, serine protease (Ssp)]
      and especially protein A (Spa). Furthermore, the pattern of proteins secreted by
      both mutants was strikingly different from that of the wild-type strain.
      Transcriptional fusions showed that expression of hla, ssp and spa was higher in
      both mutants than in the wild-type strain, indicating that the arl operon
      decreases the production of virulence factors by downregulating the transcription
      of their genes. The arl mutation did not change spa expression in an agrA mutant
      or in a sarA mutant, suggesting that both the sarA and the agr loci are required
      for the action of arl on spa. Northern blot analyses indicated that the arl
      mutation increased the synthesis of both RNA II and RNA III, but decreased sarA
      transcription. Finally, arl was not autoregulated, but its expression was
      stimulated by agr and sarA. These results suggest that the Arl system interacts
      with both agr and sarA regulatory loci to modulate the virulence regulation
      network.

PMID- 11454218
TI  - A variable genetic island specific for Neisseria gonorrhoeae is involved in
      providing DNA for natural transformation and is found more often in disseminated
      infection isolates.
AB  - Neisseria gonorrhoeae (the gonococcus) is the causative agent of the sexually
      transmitted disease gonorrhoea. Most gonococcal infections remain localized to
      the genital tract but, in a small proportion of untreated cases, the bacterium
      becomes systemic to produce the serious complication of disseminated gonococcal
      infection (DGI). We have identified a large region of chromosomal DNA in N.
      gonorrhoeae that is not found in a subset of gonococcal isolates (a genetic
      island), in the closely related pathogen, Neisseria meningitidis or in commensal
      Neisseria that do not usually cause disease. Certain versions of the island carry
      a serum resistance locus and a gene for the production of a cytotoxin; these
      versions of the island are found preferentially in DGI isolates. All versions of
      the genetic island encode homologues of F factor conjugation proteins, suggesting
      that, like some other pathogenicity islands, this region encodes a conjugation
      like secretion system. Consistent with this hypothesis, a wild-type strain
      released large amounts of DNA into the medium during exponential growth without
      cell lysis, whereas an isogenic strain mutated in a peptidoglycan hydrolase gene
      (atlA) was drastically reduced in its ability to donate DNA for transformation
      during growth. This genetic island constitutes the first major discriminating
      factor between the gonococcus and the other Neisseria and carries genes for
      providing DNA for genetic transformation.

PMID- 11454219
TI  - The cytosolic HinT protein of Mycoplasma hominis interacts with two membrane
      proteins.
AB  - Histidine triad nucleotide-binding (HinT) proteins are dimeric proteins that bind
      to purines and are found in all three kingdoms: the eukarya, bacteria and
      archaea. In eukaryotes, HinT proteins have been detected intracellularly, but
      their function is unknown. Until now, knowledge about HinT proteins in
      prokaryotes was restricted to sequence similarities and nucleotide-binding
      studies. In this study, we provide evidence that, in the cell wall-less
      prokaryote, Mycoplasma hominis, the gene encoding the HinT protein forms an
      operon with two other genes. These genes encode the species-specific membrane
      proteins, P60 and P80, which are associated within the mycoplasma membrane. The
      finding that HinT interacts with this complex by binding to P80 provides novel
      insight into the organization of bacterial HinT proteins.

PMID- 11454220
TI  - Abiotic stress in plants.

PMID- 11454221
TI  - Abiotic stress signal transduction in plants: Molecular and genetic perspectives.
AB  - Low temperature, drought and salinity are major adverse environmental factors
      that limit plant productivity. Understanding the mechanisms by which plants
      perceive and transduce these stress signals to initiate adaptive responses is
      essential for engineering stress-tolerant crop plants. Molecular and biochemical
      studies suggest that abiotic stress signaling in plants involves receptor-coupled
      phosphorelay, phosphoinositol-induced Ca2+ changes, mitogen-activated protein
      kinase cascades and transcriptional activation of stress-responsive genes. In
      addition, protein posttranslational modifications and adapter or scaffold
      mediated protein-protein interactions are also important in abiotic stress signal
      transduction. Most of these signaling modules, however, have not been genetically
      established to function in plant abiotic stress signal transduction. To overcome
      the scarcity of abiotic stress-specific phenotypes for conventional genetic
      screens, molecular genetic analysis using stress-responsive promoter-driven
      reporter is suggested as an alternative approach to genetically dissect abiotic
      stress signaling networks in plants.

PMID- 11454222
TI  - The characterization of LeNUC1, a nuclease associated with leaf senescence of
      tomato.
AB  - Induction of nuclease and RNase activities, together with decreases in nucleic
      acid content are considered to be characteristics of senescence in higher plants.
      However, little is known about the specific identities or functions of the
      enzymes involved or the mechanisms controlling their activation. Here we report
      the identification of a 41-kDa-tomato nuclease, LeNUC1, which is specifically
      induced during tomato leaf senescence but not in ripening fruits. LeNUC1 is a
      glycoprotein, which can degrade both RNA and DNA and has optimal activity at pH
      7.5-8. EDTA inhibits the activity of LeNUC1, while the addition of Co2+ or Mn2+
      can restore its activity in the presence of the chelating agent. Interestingly,
      the activity of LeNUC1 is also induced in young leaves upon treatment with
      ethylene, which is known to be a senescence-promoting hormone in tomato.
      Constitutive activity of a 39-kDa nuclease, LeNUC2, similar in its biochemical
      requirements to LeNUC1, was also detected. LeNUC2 is not induced by ethylene and
      does not seem to be glycosylated. Based on their characteristics, LeNUC1 and
      LeNUC2 can be classified as Nuclease I enzymes. LeNUC1 may be involved in nucleic
      acid metabolism during tomato leaf senescence.

PMID- 11454223
TI  - Effect of iron on activity of soybean multi-subunit acetyl-coenzyme A
      carboxylase.
AB  - Multi-subunit acetyl-coenzyme A carboxylase (MS-ACCase; EC 6.4.1.2) isolated from
      soybean chloroplasts is a labile enzyme that loses activity during purification.
      We found that incubating the chloroplast stromal fraction under anaerobic
      conditions or in the presence of 5 mM FeSO4 stimulated ACCase (acetyl-CoA-
      >malonyl-CoA) and carboxyltransferase (malonyl-CoA-->acetyl-CoA) activity. Fe
      stimulation of activity was associated with 59Fe binding to a stromal protein
      fraction. ACCase and carboxyltransferase activities measured in the stromal
      protein fraction containing bound 59Fe were 2-fold and 6-fold greater,
      respectively, than the control (stromal fraction not pretreated with FeSO4).
      Superose 6 gel filtration chromatography indicated 59Fe comigrated with stromal
      protein of approximately 180 kDa that exhibited carboxyltransferase activity, but
      lacked ACCase activity. Anion exchange (Mono-Q) chromatography of the Superose 6
      fraction yielded a protein peak that was enriched in carboxyltransferase activity
      and contained protein-bound 59Fe. Denaturing gels of the Mono-Q fraction
      indicated that the 180-kDa protein was composed of a 56-kDa subunit that was
      bound by an antibody raised against a synthetic beta-carboxyltransferase (beta
      CTase) peptide. Incubation of the Mono-Q carboxyltransferase fraction with
      increasing concentrations of iron at a fixed substrate concentration resulted in
      increased initial velocities that fit well to a single rectangular three
      parameter hyperbola (v=vo+Vmax[FeSO4]/Km+[FeSO4]) consistent with iron
      functioning as a bound activator of catalysis. UV/Vis spectroscopy of the
      partially purified fraction before and after iron incubation yielded spectra
      consistent with a protein-bound metal cluster. These results suggest that the
      beta-CTase subunit of MS-ACCase in soybean chloroplasts is an iron-containing
      enzyme, which may in part explain its labile nature.

PMID- 11454224
TI  - Temporal and tissue localization of a cowpea (Vigna unguiculata) cystatin.
AB  - A cowpea (Vigna unguiculata L. Walpers cv. Pitiuba) cystatin was analysed to
      determine its localization during development and germination of cowpea seeds,
      using western blotting with a specific antiserum. The pattern of immunoreactive
      proteins changed during development, with the major reactive bands present in
      dried seeds being mobilized after a 62-h period of imbibition.
      Immunohistochemical analysis revealed that cowpea cystatin is distributed in both
      embryonic axes and cotyledons with the highest level being present in the outer
      cell walls of the adaxial surface of the cotyledons.

PMID- 11454225
TI  - Differential aluminum tolerance in soybean: An evaluation of the role of organic
      acids.
AB  - The role of organic acids in aluminum (Al) tolerance has been the object of
      intensive research. In the present work, we evaluated the roles of organic acid
      exudation and concentrations at the root tip on Al tolerance of soybean. Exposing
      soybean seedlings to Al3+ activities up to 4.7 &mgr;M in solution led to
      different degrees of restriction of primary root elongation. Al tolerance among
      genotypes was associated with citrate accumulation and excretion into the
      external media. Citrate and malate efflux increased in all genotypes during the
      first 6 h of Al exposure, but only citrate efflux in Al-tolerant genotypes was
      sustained for an extended period. Tolerance to Al was correlated with the
      concentration of citrate in root tips of 8 genotypes with a range of Al
      sensitivities (r2=0.75). The fluorescent stain lumogallion indicated that more Al
      accumulated in root tips of the Al-sensitive genotype Young than the Al-tolerant
      genotype PI 416937, suggesting that the sustained release of citrate from roots
      of the tolerant genotype was involved in Al exclusion. The initial stimulation of
      citrate and malate excretion and accumulation in the tip of all genotypes
      suggested the involvement of additional tolerance mechanisms. The experiments
      included an examination of Al effects on lateral root elongation. Extension of
      lateral roots was more sensitive to Al than that of tap roots, and lateral root
      tips accumulated more Al and had lower levels of citrate.

PMID- 11454226
TI  - Involvement of multiple cis-elements in the regulation of GA responsive
      promoters: Definition of a new cis-element in the Amy32b gene promoter of barley
      (Hordeum vulgare).
AB  - The Amy32b gene is a member of the low-pI alpha-amylase gene family of barley,
      whose expression is tightly regulated by hormones in the aleurone layer. Four cis
      elements are known to be important for the GA induction of this gene: GARE,
      amylase box, pyrimidine box, and O2S. These sequences are located between -101
      and -149 relative to the transcription start site. In the present work, we have
      created a series of Amy32b promoter-GUS reporter constructs introducing mutations
      in the -79 to -93 region. Using a transient expression system, we have
      functionally defined an additional region (-81 to -89) essential for the GA
      activation of the Amy32b promoter. This region is highly conserved among barley,
      wheat, and wild oat low-pI alpha-amylase promoters. Interestingly, in contrast
      with the variability in the relative distances among other cis-elements, this
      region maintains a nearly constant distance to GARE, which suggests that the
      function of these elements might be coupled. The involvement of this and other
      sequences in the transactivation of Amy32b by a transcription factor, GAMyb, has
      also been studied. Our results indicate that the only indispensable element for
      the GAMyb transactivation of the alpha-amylase promoter is GARE. The present work
      brings new evidence to the proposed model that considers the GAMyb-GARE
      interaction as a critical point for the GA induction of alpha-amylase genes, but
      also strengthens the notion that multiple sequences are required for full
      regulation of alpha-amylase promoters.

PMID- 11454227
TI  - Identification of a putative Solanum tuberosum transcriptional coactivator up
      regulated in potato tubers by Fusarium solani f. sp. eumartii infection and
      wounding.
AB  - Coadaptors or coactivators are a new class of transcription factors capable of
      interconnecting a regulator DNA-binding protein with a component of the basal
      transcription machinery allowing transcriptional activation to proceed. We report
      the identification of a novel Solanum tuberosum ssp. tuberosum putative
      transcription coactivator, named StMBF1 (Solanum tuberosum multiprotein bridging
      factor 1). The StMBF1 cDNA was isolated from a Fusarium solani f. sp. eumartii
      infected potato tuber cDNA library, using a differential screening approach.
      StMBF1 is up-regulated during fungal attack as well as on wounding. A Fusarium
      elicitor source and ethylene precursor and salicylic acid also regulate StMBF1
      expression. The precise role of StMBF1 during the plant response against
      environmental stresses remains to be elucidated.

PMID- 11454228
TI  - Overexpression of a heterologous sam gene encoding S-adenosylmethionine
      synthetase in flax (Linum usitatissimum) cells: Consequences on methylation of
      lignin precursors and pectins.
AB  - The Arabidopsis thaliana sam1 gene encoding S-adenosylmethionine synthetase (EC
      2.5.1.6) was transferred to flax (Linum usitatissimum) cells via Agrobacterium
      tumefaciens. This enzyme catalyses the conversion of methionine to S
      adenosylmethionine (SAM), the major methyl group donor in living cells. The aim
      of this work was to study the consequences of an increased SAM-synthetase (SAM-S)
      activity in transgenic cell lines on both the production of mono- and
      dimethoxylated lignin monomers and the degree of methylesterification of pectins.
      Hypocotyls were cocultivated with Agrobacterium tumefaciens strain GV3101
      (pGV2260) harbouring the pO35SSAM binary vector carrying the sam1 gene under the
      control of the 35S promoter and the nptII gene for selection of putative
      transformed cells. Most of the transgenic cell lines exhibited a significant (up
      to 3.2-fold) increase in SAM-S activity compared to the controls. The results
      showed that for the cell lines analysed this transformation had no effect on
      caffeic acid O-methyltransferase (COMT, EC 2.1.1.68) in vitro activity, degree of
      methoxylation of lignin precursors or lignin deposition, pectin methyltransferase
      (PMT, EC 2.1.1) in vitro activity, but led to an increase of pectin
      methylesterification in friable and fast-growing transgenic cell lines.

PMID- 11454229
TI  - Regulation of 7S globulin gene expression in zygotic and somatic embryos of oil
      palm.
AB  - We describe here the characterization and expression analysis of the oil palm
      GLO7A gene encoding a 7S globulin protein. Previous work carried out in our
      laboratory showed that 7S globulins accumulate in the oil palm zygotic embryo
      mostly between the 14 and 17 weeks after pollination. To investigate further the
      regulation of 7S globulin gene expression in both zygotic and somatic embryos of
      oil palm, we isolated a cDNA clone, GLO7A, for use as a probe in northern
      hybridization studies. The nucleotide sequence of the GLO7A cDNA reveals that it
      encodes a polypeptide of 572 amino acids (66 kDa) sharing significant sequence
      similarities with various vicilin-like proteins of both dicotyledonous and
      monocotyledonous plants. Northern hybridization analysis shows that 7S globulin
      mRNA accumulation in zygotic embryos is temporally regulated with a profile
      essentially the same as that observed at the protein level. In somatic embryos,
      7S globulin proteins were found to occur in amounts approximately 80 times lower
      than those in zygotic embryos. This lack of 7S globulin protein accumulation in
      somatic embryos is mirrored by a low accumulation of the GLO7A mRNA. The in vitro
      production of 7S globulins (and more generally salt-soluble proteins) is improved
      by the addition to the culture medium of arginine, sucrose and ABA, the effects
      of these 3 components being additive. To investigate further the action of the 3
      molecules of interest, we performed parallel studies on mRNA and protein
      abundance. Our studies of transcript accumulation suggest that ABA and sucrose
      act directly on mRNA synthesis or stability; however, it appears that there are
      also translational or post-translational regulatory factors which act to limit
      protein accumulation in somatic embryos. The GLO7A gene promoter was cloned and
      sequenced to assess whether GLO7A gene expression might be modulated by cis
      acting promoter elements related to those found in other plants. Two motifs
      resembling ABREs (ABA-responsive elements) and one motif resembling a seed
      specific promoter element were identified within the 5' flanking sequence.

PMID- 11454230
TI  - In vivo sucrose stimulation of colour change in citrus fruit epicarps:
      Interactions between nutritional and hormonal signals.
AB  - During ripening, citrus fruit-peel undergoes 'colour break', a process
      characterized by the conversion of chloroplast to chromoplast. The process
      involves the progressive loss of chlorophylls and the gain of carotenoids,
      changing peel colour from green to orange. In the present work, the in vivo and
      in vitro effects of supplemented nutrients (sucrose and nitrogen) and
      phytohormones (gibberellins [GA] and ethylene) on colour change in fruit epicarp
      of Satsuma mandarin (Citrus unshiu (Mak.) Marc., cv. Okitsu), were studied. The
      rate of colour break was correlated positively with sucrose content and
      negatively with nitrogen content. The removal of leaves blocked natural sucrose
      build-up and nitrogen reduction in the peel. Defoliation also inhibited
      chlorophyll disappearance and carotenoid accumulation, thereby preventing colour
      break. In vivo sucrose supplementation promoted sucrose accumulation and advanced
      colour break. In both in vivo and in vitro experiments, colour change promoted by
      sucrose was unaffected by ethylene but delayed by GA3. In non-supplemented
      plants, ethylene accelerated colour break while GA3 had no detectable effects.
      Ethylene inhibitors effectively counteracted the sucrose effects on colour
      change. Collectively, these results suggest that the chloroplast to chromoplast
      conversion in citrus fruit epicarps is stimulated by sucrose accumulation. The
      sugar regulation appears to operate via ethylene, whereas GA may act as a
      repressor of the sucrose-ethylene stimulation.

PMID- 11454231
TI  - The ectopic overexpression of a citrus gibberellin 20-oxidase enhances the non-13
      hydroxylation pathway of gibberellin biosynthesis and induces an extremely
      elongated phenotype in tobacco.
AB  - Transgenic plants of Nicotiana tabacum overexpressing a gibberellin (GA) 20
      oxidase cDNA (CcGA20ox1) from citrus, under the control of the 35S promoter, were
      taller (up to twice) and had larger inflorescences and longer flower peduncles
      than those of control plants. Hypocotyls of transgenic seedlings were also longer
      (up to 4 times), and neither the seedlings nor the growing plants elongated
      further after application of GA3. Hypocotyl and stem lengths were reduced by
      application of paclobutrazol, and this inhibition was reversed by exogenous GA3.
      The ectopic overexpression of CcGA20ox1 enhanced the non-13-hydroxylation pathway
      of GA biosynthesis leading to GA4, apparently at the expense of the early-13
      hydroxylation pathway. The level of GA4 (the active GA from the non-13
      hydroxylation pathway) in the shoot of transgenic plants was 3-4 times higher
      than in control plants, whereas that of GA1, formed via the early-13
      hydroxylation pathway (the main GA biosynthesis pathway in tobacco), decreased or
      was not affected. GA4 applied to the culture medium or to the expanding leaves
      was found to be at least equally active as GA1 on stimulating hypocotyl and stem
      elongation of tobacco plants. The results suggest that the tall phenotype of
      tobacco transgenic plants was due to their higher content of GA4, and that the GA
      response was saturated by the presence of the transgene.

PMID- 11454232
TI  - The cytokinin 2-isopentenyladenine causes partial reversion to skotomorphogenesis
      and induces formation of prolamellar bodies and protochlorophyllide657 in the
      lip1 mutant of pea.
AB  - When grown in darkness the photomorphogenic lip1 mutant of pea (Pisum sativum L.)
      has a slender stem, expanded leaves, prolamellar body (PLB) lacking plastids with
      the size of chloroplasts and a low level of phytochrome A. The lack of PLBs in a
      dark-grown material (lip1) created a possibility to further study the regulation
      of their formation in relation to plant development. Inclusion of a cytokinin, 2
      isopentenyladenine (2iP), in a medium supporting growth of the pea seedlings in
      darkness was found to reduce epicotyl length in the wild type. In lip1 the
      formation of a slender stem was inhibited and a short epicotyl developed.
      Furthermore, leaf expansion was inhibited, the plastid size reduced and the
      formation of PLBs induced. The PLB formation in lip1 was not accompanied by an
      increase in the amount of protochlorophyllide (Pchlide) or Pchilde oxidoreductase
      (POR). In the presence of 2iP the level of phytochrome A protein was increased in
      lip1 and the POR mRNA levels decreased in both lip1 and wild-type plants. The
      chloroplast characteristic trans-3-hexadecenoate acyl group of
      phosphatidylglycerol, present in the plastids of dark-grown lip1, was not
      influenced by 2iP. Thus, not all photomorphogenic processes reacted similarly in
      the lip1 mutant, but leaf expansion and plastid differentiation, including PLB
      formation, seemed to be regulated by the same signal transduction chain.
      Exogenously applied brassinolide could rescue neither dark- nor light-grown
      defects of the lip1 mutant. Thus, cytokinins but not brassinolides seem to be
      involved in the regulation of certain characteristic traits of skotomorphogenesis
      in pea, including plastid development and PLB formation.

PMID- 11454233
TI  - The last step of the ethylene biosynthesis pathway in turnip tops (Brassica rapa)
      seeds: Alterations related to development and germination and its inhibition
      during desiccation.
AB  - The involvement of ethylene in zygotic embryogenesis is a little known aspect of
      the growth and development in higher plants. In the present work, we study the
      alterations of the last step of the ethylene biosynthesis pathway during the
      formation period of turnip tops (Brassica rapa cv. Rapa) seeds and its
      repercussions in the germination process and post-germinative growth. For this,
      we chose 11 different phases of silique development, the first being the recently
      fertilized pistil and the last being the silique just prior to its dehiscence
      (ca. 2 months post-anthesis). In the 11 phases, ethylene production was detected
      in both whole silique (with or without seeds) and in the seeds enclosed by the
      silique wall. The levels of ACC, ACO and ethylene production proved high in seeds
      belonging to: (1) the pod in the very early phases, when the seeds were growing
      but without photosynthetic competence; (2) the silique at maximum growth, in
      which the seeds will initiate desiccation and loss of photosynthetic activity.
      During the phases prior to dehiscence, there was a marked inhibition in the last
      step of the ethylene biosynthesis pathway. In viable dry seeds, no ACO activity
      was detected and the ACC levels were 4-fold lower than at the onset of the
      silique senescence. Germination brings about a net synthesis of ACC with respect
      of the stores dry seed. This fact, together with other results presented in this
      work, point towards, as in other seeds, a dependence of ethylene synthesis for
      radicle emergence. The possible role played by the silique wall in the control of
      ethylene biosynthesis during zygotic embryogenesis, as well as the participation
      of ethylene as a hormonal signal in the triggering of seed desiccation in
      Brassica rapa cv. Rapa, are discussed in depth.

PMID- 11454234
TI  - 4-Hydroxybenzyl alcohol accumulates in suspension-cell cultures and inhibits
      somatic embryogenesis in carrot.
AB  - Somatic embryogenesis in carrot (Daucus carota L.) is strongly inhibited by
      certain factors that accumulate in culture medium of high-density cultures of
      embryogenic cells. We previously identified 4-hydroxybenzyl alcohol (4HBA) as one
      of the inhibitory factors. In this study, we analyzed the accumulation pattern of
      4HBA in the cultures of carrot suspension cells. When somatic embryogenesis was
      induced by culturing embryogenic cells in phytohormone-free Murashige and Skoog
      medium at various initial cell densities, 4HBA accumulated in the culture medium.
      The concentration of 4HBA in high cell density cultures was higher than in low
      cell density cultures. The accumulation of 4HBA in high cell density cultures was
      rapid during the early days of culture. This rapid accumulation of 4HBA in high
      cell density cultures might result in the strong inhibition of somatic
      embryogenesis. The production of 4HBA decreased as the somatic embryos developed.
      In addition, embryogenic cells released larger amount of 4HBA into the culture
      medium compared with non-embryogenic cells. These results suggest that the
      production of 4HBA is both related to embryogenic competence and developmentally
      regulated during somatic embryogenesis.

PMID- 11454235
TI  - Ozone treatment affects pigment precursor metabolism in pine seedlings.
AB  - Five-week-old seedlings of Pinus halepensis Mill. and Pinus brutia Ten. were
      exposed to air polluted with ozone (O3) (250 nl l-1, 12 h day-1 for 4 days) or to
      ambient air containing ca 10-20 nl l-1 O3, in the light (180 &mgr;mol m-2 s-1
      photosynthetic photon flux density [PPFD], 12 h day-1) and then fed for 24 h in
      the light (100 &mgr;mol m-2 s-1 PPFD) with various radioactive precursors of
      chlorophyll (Chl) and carotene biosynthesis: 5-[4-14C]-aminolevulinic acid (14C
      ALA), L-[14C(U)]-glutamic acid (14C-Glu), or D,L-[2-14C]-mevalonic acid (14C
      MVA). Pigments were then extracted from cotyledons and fully expanded needles.
      Chl a and carotene were separated by thin-layer chromatography and high
      performance liquid chromatography and their specific activities were determined.
      14C-ALA and 14C-Glu labels were incorporated into Chl a and carotene. Exposure to
      O3 did not inhibit incorporation of 14C-ALA into Chl a molecules, but hydrolysis
      of Chl a showed that O3 inhibited phytol labelling of Chl a. Labelling of
      carotene was also inhibited by O3, but not when 14C-MVA was used as the label.
      These data suggest that O3 treatment inhibits (directly or indirectly) the
      biosynthesis of isoprenoids from products of ALA and Glu metabolism in the
      plastid, but not from MVA in the cytosol. This inhibition was more prominent when
      14C-ALA was used as the label than when 14C-Glu was the labelling precursor. A
      significant increase in pheophorbide a, a tetrapyrrole component of Chl a
      labelling, and a concomitant decrease in phytol labelling was observed following
      incubation of O3-treated pine seedlings with 14C-ALA and 14C-Glu. Stronger
      inhibition of carotene biosynthesis and activation of Chl a tetrapyrrole
      labelling by 14C-ALA (in comparison with 14C-Glu) indicated that exposure to O3
      inhibits the conversion of ALA to Glu as the first step in ALA catabolism. These
      results also suggested a more intensive Glu metabolism (in comparison with ALA)
      for carotene biosynthesis in the cytosol, as well as cooperation between two
      pathways of isopentenyl diphosphate biosynthesis.

PMID- 11454236
TI  - Plasticity of petioles of white clover (Trifolium repens) to blue light.
AB  - Petiole response of white clover to variations in blue light (BL) was studied on
      the main axis and on primary and secondary branches. The objectives of the
      present work were to determine (1) the time course of petiole response to BL and
      (2) whether these responses were dependent on petiole location. Under BL, clover
      had shorter petioles, and the switch to conditions without BL increased the
      length of forthcoming petioles. The fitting of a logistic function was used to
      compare the effect of BL on final petiole length, maximum elongation rate and the
      duration of petiole elongation between axes and phytomers. Petiole response to BL
      was not dependent on its location within the plant (axis type or phytomer
      position along the axis). A reduction in BL induced a rapid increase in leaf
      elongation rate, despite a small decrease in the duration of petiole elongation.
      Moreover, petiole response was dependent on petiole stage of development: the
      increase in the maximum rate of petiole elongation was inversely proportional to
      the petiole stage of development at the time of the switch. We conclude that the
      effects of BL on petiole elongation were not dependent on its position within the
      plant, whereas internode elongation resulted from the integration of light
      environment at the plant level. The difference between the responses of
      orthotropic and plagiotropic organs of clover to BL is discussed in relation to
      their structural function and localisation in the canopy.

PMID- 11454237
TI  - Genomic organization and single-nucleotide polymorphism map of desmuslin, a novel
      intermediate filament protein on chromosome 15q26.3.
AB  - BACKGROUND: Desmuslin is an alpha-dystrobrevin-interacting protein expressed
      primarily in heart and skeletal muscle. The desmuslin protein interacts with and
      is closely related to desmin, a protein encoded by a locus mutated in some forms
      of hereditary distal myopathy. As a muscle-specific intermediate filament
      protein, desmuslin is also a candidate for myopathies of unknown etiology.
      RESULTS: The desmuslin gene was localized to chromosome 15q26.3 by electronic
      screening of the human DNA sequence database. Primer pairs were designed to
      amplify the 5 exons of the desmuslin gene in 11 overlapping DNA segments. The
      desmuslin gene was screened for mutations in 71 patients with various forms of
      myopathy for which there was no known cause. In this analysis, 10 common and 2
      rare amino acid altering single-nucleotide polymorphisms were identified, all of
      which were seen in a control population of individuals thus making these unlikely
      causes of the phenotype. Interestingly, one of the single-nucleotide
      polymorphisms found in a patient resulted in a premature stop codon in the first
      exon. The nonsense mutation was also detected in the patient's unaffected father
      and one unaffected control; it was detected in 0.44% (2/454) of unrelated
      chromosomes and is therefore predicted to have a homozygous frequency of 0.002%.
      CONCLUSION: No causative mutations were found in the desmuslin gene. However, the
      single-nucleotide polymorphisms mapped in this study represent a well-mapped
      group that can be used for disequilibrium studies of this region of chromosome
      15q26.3.

PMID- 11454238
TI  - Sub-inhibitory concentrations of vancomycin prevent quinolone-resistance in a
      penicillin-resistant isolate of Streptococcus pneumoniae.
AB  - BACKGROUND: The continuous spread of penicillin-resistant pneumococci represents
      a permanent threat in the treatment of pneumococcal infections, especially when
      strains show additional resistance to quinolones. The main objective of this
      study was to determine a treatment modality impeding the emergence of quinolone
      resistance. RESULTS: Exposure of a penicillin-resistant pneumococcus to
      increasing concentrations of trovafloxacin or ciprofloxacin selected for mutants
      resistant to these drugs. In the presence of sub-inhibitory concentrations of
      vancomycin, development of trovafloxacin-resistance and high-level ciprofloxacin
      resistance were prevented. CONCLUSIONS: Considering the risk of quinolone
      resistance in pneumococci, the observation might be of clinical importance.

PMID- 11454239
TI  - Reliability, validity and psychometric properties of the Greek translation of the
      Center for Epidemiological Studies-Depression (CES-D) Scale.
AB  - INTRODUCTION: The aim of the current study was to assess the reliability,
      validity and psychometric properties of the Greek translation of the Center for
      Epidemiological Studies- Depression Scale (CES-D). METHODS: 40 depressed patients
      29.65 +/- 9.38 years old, and 120 normal controls 27.23 +/- 10.62 years old
      entered the study. In 20 of them (12 patients and 8 controls) the instrument was
      re-applied 1-2 days later. Translation and Back Translation was made. Clinical
      Diagnosis was reached by consensus of two examiners with the use of the SCAN
      v.2.0 and the IPDE. Statistical Analysis included ANOVA, the Pearson Product
      Moment Correlation Coefficient, Principal Components Analysis and Discriminant
      Function Analysis and the calculation of Cronbach's alpha (alpha) RESULTS: Both
      Sensitivity and specificity exceed 90.00 at 23/24, Chronbach's alpha for the
      total scale was equal to 0.95. Factor analysis revealed three factors (positive
      affect, irritability and interpersonal relationships, depressed affect and
      somatic complains). The test-retest reliability was satisfactory (Pearson's R
      between 0.45 and 0.95 for individual items and 0.71 for total score). CONCLUSION:
      The Greek translation of the CES-D scale is both reliable and valid and is
      suitable for clinical and research use with satisfactory properties. Its
      properties are similar to those reported in the international literature. However
      one should always have in mind the limitations inherent in the use of self-report
      scales.

PMID- 11454240
TI  - Delayed union of femoral fractures in older rats:decreased gene expression.
AB  - BACKGROUND: Fracture healing slows with age. While 6-week-old rats regain normal
      bone biomechanics at 4 weeks after fracture, one-year-old rats require more than
      26 weeks. The possible role of altered mRNA gene expression in this delayed union
      was studied. Closed mid-shaft femoral fractures were induced followed by
      euthanasia at 0 time (unfractured) or at 1, 2, 4 or 6 weeks after fracture in 6
      week-old and 12-15-month-old Sprague-Dawley female rats. mRNA levels were
      measured for osteocalcin, type I collagen alpha1, type II collagen, bone
      morphogenetic protein (BMP)-2, BMP-4 and the type IA BMP receptor. RESULTS: For
      all of the genes studied, the mRNA levels increased in both age groups to a peak
      at one to two weeks after fracture. All gene expression levels decreased to very
      low or undetectable levels at four and six weeks after fracture for both age
      groups. At four weeks after fracture, the younger rats were healed
      radiographically, but not the older rats. CONCLUSIONS: (1) All genes studied were
      up-regulated by fracture in both age groups. Thus, the failure of the older rats
      to heal promptly was not due to the lack of expression of any of the studied
      genes. (2) The return of the mRNA gene expression to baseline values in the older
      rats prior to healing may contribute to their delayed union. (3) No genes were
      overly up-regulated in the older rats. The slower healing response of the older
      rats did not stimulate a negative-feedback increase in the mRNA expression of
      stimulatory cytokines.

PMID- 11454241
TI  - The rise and fall of malarial sporozoite rates in Anopheles gambiae s.l. and An.
      funestus in north-eastern Tanzania, between 1934 and 1999.
AB  - The proportion of Anopheles mosquitoes found to be carrying Plasmodium
      sporozoites, usually called the 'malarial sporozoite rate', has often been used
      as a measure of mosquito infectivity. Although the sporozoite rates found in
      Anopheles gambiae and An. funestus in Muheza, north-eastern Tanzania, showed a
      marked decline between the mid-1930s and the mid-1970s, they then began to rise
      again. This fall and rise in mosquito infectivity is attributed to the widespread
      use of antimalarial drugs, which initially tended to reduce the infectivity of
      patients for mosquitoes, and the subsequent development of resistance to these
      drugs in the malarial parasites. The rise observed in the sporozoite rates in
      Muheza in the 1980s-1990s may be attributed to widespread resistance of P.
      falciparum to chloroquine, until recently the drug of choice for the treatment of
      malaria in Tanzania. Changes in the survival rates, abundance, or predominant
      species of the mosquito vectors are unlikely to have influenced the pattern
      observed. The role of antimalarial drugs in malaria transmission risk is
      discussed.

PMID- 11454242
TI  - Influence of clinical presentation on the efficacy of a short course of
      pentamidine in the treatment of cutaneous leishmaniasis in French Guiana.
AB  - The cure 'rates' achieved using intramuscular pentamidine isethionate (two
      injections of 4 mg/kg separated by an interval of 48 h) were investigated in
      French Guiana, in 198 consecutive patients with cutaneous leishmaniasis caused by
      Leishmania braziliensis guyanensis. One aim was to see if initial clinical
      presentation could be used to predict treatment failure. The cure rate after one
      course of pentamidine isethionate was 87% and almost all (80%) of the treatment
      failures responded to an identical second course. Although many of the patients
      complained of adverse effects, most commonly of pain at the injection site (54%),
      none of these effects was severe. Although frequently associated with discomfort,
      the two-injection course, giving a total of 8 mg pentamidine isethionate/kg,
      appears to be an effective treatment for cutaneous leishmaniasis in French
      Guiana. The observation of satellite papules on presentation was associated with
      a significantly increased risk of failure of the first course of treatment (P =
      0.01), with an odds ratio (and 95% confidence interval) estimated at 3.5 (1.3
      11.1), after adjusting for other clinical presentations and lesion size and
      number. The presence of satellite papules perhaps indicates that the patient's
      immune system is unable to control the progression of the parasite. Patients with
      more than three lesions were also less likely to be cured after one course of
      pentamidine than those with fewer lesions (P = 0.01).

PMID- 11454243
TI  - Fertility of the cysts of Echinococcus granulosus in domestic herbivores from
      Benghazi, Libya, and the reactivity of antigens produced from them.
AB  - Unilocular cysts produced by Echinococcus granulosus were recovered from 110
      domestic herbivores (60 sheep, 25 cattle, 20 goats and five camels) slaughtered
      in Benghazi. The proportion of the cysts from the sheep found to be fertile (75%)
      was higher than that of the cysts from the goats (55%), camels (40%), or cattle
      (0%). When tested in indirect haemagglutination assays (IHA) with eight sera from
      human cases of cystic echinococcosis, the fluid from the cattle cysts never gave
      a positive reaction. Antigens in the fluids collected from sheep or goat cysts
      did react with the sera, with antigens from each of the two sources giving
      similar titres with each serum. However, crude somatic antigens (prepared from
      protoscolices and brood capsules collected from sheep cysts) appeared to be more
      sensitive for the immunodiagnosis of human cystic echinococcosis than the cyst
      fluid antigens.

PMID- 11454244
TI  - The potential of rapid screening methods for Schistosoma mansoni in western
      Kenya.
AB  - Data from 46 schools in western Kenya were used to investigate the performance of
      school-based questionnaires, on reported blood in stool and water-contact
      patterns, as indicators of the prevalence of human infection with Schistosoma
      mansoni. Prevalence of infection was associated with the prevalence of self
      reported blood in stool, recent history of swimming and recent history of
      fishing. It was shown that use of a threshold of 30% of subjects reporting blood
      in stool would identify 42.9% of the 'high-prevalence' schools (i.e. prevalence >
      or = 50%) and 87.5% of the 'low-prevalence' schools (i.e. prevalence < 50%). A
      threshold of 25% reporting swimming would identify 57.1% and 93.7% of the high-
      and low-prevalence schools, respectively. Blood in stool appears to be too coarse
      an indicator to identify schools for mass treatment correctly. Although the use
      of multiple questions improved the diagnostic performance of the questionnaire in
      identifying the high-prevalence schools, it was unclear how questions can best be
      combined in other settings. However, there is a direct relationship between
      prevalence of S. mansoni infection and distance of the school from the lakeshore;
      analysis indicated that use of a threshold of 5 km from the lakeshore would
      correctly identify most (90%) of both the low- and high-prevalence schools.
      Distance to the lakeshore may therefore be used to screen schools in much of East
      Africa (i.e. those areas close to the Great Lakes where the infection is known to
      be prevalent and where much of the region's population is concentrated). In other
      areas of transmission, such as irrigation areas, further studies are still
      required.

PMID- 11454245
TI  - Bulinus nyassanus is an intermediate host for Schistosoma haematobium in Lake
      Malawi.
AB  - At Cape Maclear on the Nankumba Peninsula, close to the southern end of Lake
      Malawi, Schistosoma haematobium is highly prevalent in the local people and many
      tourists become infected with this parasite each year. A 'Bilharzia Control
      Programme' was initiated in this area in August 1998, as a development
      collaboration between the Government of Malawi, the Danish Agency for Development
      Assistance (Danida), and the Danish Bilharziasis Laboratory. Although Bulinus
      globosus is a known host for S. haematobium, B. nyassanus has not previously been
      incriminated as an intermediate host. However, schistosome-infected B. nyassanus
      were discovered in surveys to identify transmission sites on the peninsula.
      Experimental infections of wild-caught B. nyassanus with S. haematobium proved
      successful and S. haematobium eggs were found in hamsters experimentally exposed
      to cercariae retrieved from schistosome-infected, field-collected B. nyassanus.
      These are remarkable observations since, although there are very few reports of
      diploid members of this species group being experimentally infected with S.
      haematobium, B. nyassanus is a diploid member (2n = 36) of the truncatus/tropicus
      group. Bulinus nyassanus is probably responsible for transmission in Lake Malawi,
      along rather exposed shorelines, devoid of aquatic macrophytes, with a substrate
      of sand or gravel.

PMID- 11454246
TI  - Annual single-dose diethylcarbamazine plus ivermectin for control of bancroftian
      filariasis: comparative efficacy with and without vector control.
AB  - Two intervention strategies for the control of bancroftian filariasis were
      compared in rural villages of southern India: annual mass treatment with single
      dose diethylcarbamazine plus ivermectin, either on its own or combined with
      vector control. Vector control, based on the use of polystyrene beads and
      larvivorous fishes in the major breeding sites of Culex quinquefasciatus, brought
      about a drastic and sustained reduction in vector density and man-biting rates.
      After the first round of treatment, chemotherapy alone brought about a 60% drop
      in the annual transmission potential (ATP) whereas the integrated strategy
      reduced ATP by 96% (P < 0.05). After two annual rounds of treatment, the
      reduction in ATP was similar for both strategies (91%-96%), with the prevalences
      of microfilaraemia reduced by 88%-92%. However, when drug pressure was removed in
      the third and final year of the study, transmission was resumed in the absence of
      vector control whereas no infective female mosquitoes were detected in the
      villages with vector control. Vector control, though obviously not cost-effective
      in the short term, could play an important role in an integrated programme, by
      preventing re-establishment of transmission after chemotherapy is completed.

PMID- 11454247
TI  - Studies on the macrofilarial population of Onchocerca volvulus in hyper-endemic
      villages of the Central province of Cameroon.
AB  - The population structure of Onchocerca volvulus macrofilariae was studied in
      villages of central Cameroon where onchocerciasis is hyper-endemic. One nodule
      selected at random was removed from each of 576 adult males, and examined by
      histology. The numbers of male and female worms/nodule, and the status of the
      female worms (fecund, non-fecund, or dead) were recorded. The observations were
      analysed to evaluate whether the mean numbers of worms of each category varied in
      relation to the patient's age, the level of endemicity in his village, the
      anatomical localization of the nodule, the weight of the nodule, and the total
      number of palpable nodules harboured by the patient. The results obtained were
      very similar to those reported from West Africa. The mean numbers of dead female
      worms/nodule were relatively high in the villages with the lowest levels of
      endemicity. The mean numbers of fecund females and of live males were
      significantly higher in the nodules located around the knees. These results
      provide information which might be useful in modelling the population dynamics of
      O. volvulus, and also in the context of trials of any potentially
      macrofilaricidal drugs.

PMID- 11454248
TI  - Follow-up of Ascaris lumbricoides and Trichuris trichiura infections in children
      living in a community treated with ivermectin at 3-monthly intervals.
AB  - Ivermectin treatment was administered every 3 months over a 1-year period (April
      1993-April 1994) to the whole eligible population of a village in South Cameroon
      where both Ascaris lumbricoides and Trichuris trichiura were hyper-endemic. A
      parasitological stool examination was performed before each treatment. Thirty
      children, aged 5-15 years, were not only found egg-positive for A. lumbricoides
      and/or T. trichiura before the first treatment but were also each treated and
      examined in each treatment round. Among these children, the intensity of
      infection with A. lumbricoides decreased significantly following the first
      treatment but thereafter remained steady. In contrast, the repeated ivermectin
      treatments had no significant impact on the intensity of the T. trichiura
      infections or on the prevalence of infection with T. trichiura or A. lumbricoides
      among the 30 children.

PMID- 11454249
TI  - Serological evidence for the continued presence of human rickettsioses in
      southern India.
AB  - Rickettsiosis is generally believed to have disappeared from many parts of India.
      However, the serological testing of 37 residents of southern India who presented
      with fever of unknown aetiology in 1996-1998 confirmed that spotted fever,
      epidemic/endemic typhus and scrub typhus continue to occur in southern India. The
      epidemiology and magnitude of the problem need to be evaluated.

PMID- 11454250
TI  - Seroprevalences of antibodies against thoracic proteins of three species of
      mosquito, among the residents of an area where filariasis is endemic:
      relationship with the mosquito densities.
AB  - Attempts were made to correlate the numbers of indoor-resting Culex
      quinquefasciatus, Armigeres theobold and Anopheles vagus in Raipur, Chattisgarh
      state, India, with the seroprevalences, among the city's microfilaraemic and
      'endemic normal' residents, of antibodies reacting with thoracic proteins from
      the adult females of each of these species. Overall, 6478 female mosquitoes were
      collected in about 176 man-hours spread over a 12-month period. Antibodies to Cx.
      quniquefasciatus, the commonest species and the only one to be prevalent in all
      seasons of the year, were detected in 90% of the microfilaraemic subjects and 27%
      of the endemic normal. Although Armigeres theobold only constituted 5% of the
      mosquitoes collected, 96% of the microfilaraemic subjects and 69% of the endemic
      normal subjects had antibodies against thoracic proteins of this species (almost
      50% of all the sera having high titres of such antibodies). Antibodies to An.
      vagus were detected, although almost always at very low titres, in 84% of the
      microfilaraemic subjects and 42% of the endemic normal. Thus, the seroprevalence
      of antibodies to thoracic antigens from a mosquito species bore no relationship
      with the indoor-resting densities of that species.

PMID- 11454251
TI  - Evaluation of avermectins as sandfly control agents.
AB  - The potential of avermectins as environmentally safe agents for the control of
      the sandfly vectors of Leishmania spp. was investigated in the laboratory. Female
      Phlebotomus papatasi and P. langeroni were fed either bloodmeals containing
      laboratory-grade ivermectin or sugarmeals containing a commercial-product based
      on abamectin. Low concentrations of either avermectin killed the sandflies, with
      median lethal concentrations (LC(50)) of just 13 ng ivermectin or 0.5 ng
      abamectin/ml for P. papatasi and 44 ng ivermectin or 35 ng abamectin/ml for P.
      langeroni. The feeding of female sandflies of both species with generally
      sublethal doses (LC(30)) of ivermectin in blood led to markedly reduced survival
      and fecundity (i.e. number of eggs laid/ovipositing female). However, addition of
      ivermectin to the bloodmeal (or of abamectin to the sugarmeal) of the females had
      no statistically significant effect on the proportion of their eggs that hatched.
      The results indicate that very small amounts of avermectin in their blood- or
      sugar-meals could control P. papatasi and P. langeroni, by killing many flies
      and, in the case of ivermectin, by reducing the fecundity of the survivors.

PMID- 11454252
TI  - Dermacentor andersoni: effects of repeated infestations on lymphocyte
      proliferation, cytokine production, and adhesion-molecule expression by BALB/c
      mice.
AB  - The effects of repeated infestations with Dermacentor andersoni nymphs on the
      lymphocyte functions of BALB/c mice were investigated. The in-vitro proliferation
      responses to concanavalin-A or salivary-gland molecules, the production of
      cytokines, and the expression of two adhesion molecules-leucocyte function
      associated antigen-1 (LFA-1) and very late activation-4 (VLA-4)-were all studied.
      In addition, the ability of salivary-gland extract or saliva from D. andersoni to
      modulate expression of lymphocyte adhesion molecules in vitro was determined. The
      proliferative responses of T-lymphocytes to concanavalin-A were significantly
      suppressed after first and second infestations, and significant increases in
      lymphocyte proliferation in the presence of tick salivary-gland antigen were
      observed in infested mice. After two infestations, production of interleukin-2
      was significantly decreased but that of interferon-gamma remained unchanged.
      Production of interleukin-4 and interleukin-10 was significantly enhanced in
      infested mice after both the first and second infestations. Expression of LFA-1
      and VLA-4 by lymphocytes from infested mice was suppressed. Furthermore, both a
      salivary-gland extract and the saliva of D. andersoni reduced the in-vitro
      expression of both of these adhesion molecules by lymphocytes from tick-naive
      mice.

PMID- 11454253
TI  - The prevalence of folP1 mutations associated with clinical resistance to dapsone,
      in Mycobacterium leprae isolates from South Korea.

PMID- 11454254
TI  - The P2Y12 receptor as a therapeutic target in cardiovascular disease.
AB  - Coronary thrombosis complicating rupture of atherosclerotic plaque is the
      predominant cause of acute coronary syndromes and platelets play a crucial role
      in this thrombus formation. Whilst aspirin has been successful in reducing
      cardiovascular morbidity and mortality, appreciation of its limited antiplatelet
      effects has stimulated the search for more effective antiplatelet agents. The
      thienopyridines, ticlopidine and clopidogrel, act, via metabolites, on the
      platelet ADP receptor subtype now designated P2Y(12 )(formerly P(2T), P2T (AC),
      P2Y (ADP) or P2Y(cyc)) and these agents have proven clinical efficacy. Analogues
      of the natural P2Y(12) receptor antagonist ATP have been developed that act
      directly on the receptor and have a rapid onset of action. One such antagonist,
      AR-C69931MX, is being developed for clinical use. AR-C69931MX is a potent
      antagonist of ADPinduced platelet activation, aggregation and secretion and also
      antagonises platelet responses, including procoagulant activity, induced by all
      other agonists in view of the central role of the P2Y(12) receptor in amplifying
      platelet responses. Phase II studies of intravenous AR-C69931MX in patients with
      acute coronary syndromes show that this agent has a rapid onset of action,
      rapidly achieving steady-state inhibition of platelet aggregation, with a half
      life of only a few minutes. AR-C69931MX appears to be safe and well tolerated as
      adjunctive therapy in these patients, and more effective inhibition of platelet
      function is achieved than with clopidogrel. Orally active ATP analogues are also
      being developed that may be more effective than clopidogrel. Limitations of
      platelet glycoprotein IIb/IIIa antagonists leave scope for development of
      alternative antiplatelet agents.

PMID- 11454255
TI  - Antiplatelet effects of prostacyclin and nitric oxide in patients with type I
      diabetes and ischemic or edematous retinopathy.
AB  - The aim of this study was investigate prostacyclin and nitric oxide (NO) and
      their platelet second messengers cAMP and cGMP, in patients with type I diabetes
      with or without retinopathy. We compared 20 healthy volunteers and 97 patients
      with type I diabetes: 24 with no signs of diabetic retinopathy (DR), 43 with
      ischemicproliferative DR, and 30 with edematous DR. The following parameters were
      recorded: platelet aggregometry, nitrites/nitrates, 6-keto-prostaglandin
      F(1alpha), and intraplatelet cAMP and cGMP. Platelet aggregation was greater in
      patients with edematous DR. The platelets in patients with diabetes were more
      resistant to inhibition by prostaglandin E(1) or sodium nitropruside. Nitrite
      concentration in patients with ischemic-proliferative DR was 80% lower than the
      value in healthy controls, but there was no significant difference between the
      control group and patients with edematous DR. In the latter group, stimulation of
      neutrophils with L-arginine increased nitrite + nitrate production by 44 +/-
      3.6%, whereas in patients with ischemic-proliferative DR, the increase was 9.8 +/
      0.8%. We conclude that NO production is higher in patients with type I diabetes
      and edematous retinopathy than in those with ischemic-proliferative retinopathy.
      This finding, together with the possibly greater production of free radicals, may
      explain the greater impairment of platelet function in the former patients.

PMID- 11454256
TI  - Effects of tomato extract on human platelet aggregation in vitro.
AB  - Among all fruits tested in vitro for their anti-platelet property, tomato had the
      highest activity followed by grapefruit, melon, and strawberry, whereas pear and
      apple had little or no activity. Tomato extract (20-50 microl of 100% juice)
      inhibited both ADP- and collagen-induced aggregation by up to 70% but could not
      inhibit arachidonic acid-induced platelet aggregation and concomitant thromboxane
      synthesis under similar experimental conditions. The anti-platelet components (MW
      <1000 Da) in tomatoes are water soluble, heat stable and are concentrated in the
      yellow fluid around the seeds. The active fractions were separated using gel
      filtration and HPLC. The aqueous fraction (110 000 xg supernatant) of tomatoes
      containing anti-platelet activity was subjected to gel filtration column
      chromatography (Biogel P2 column). The activity was fractionated into two peaks,
      peak-3 and peak-4 (major peak). Subsequently, peak-4 was further purified by HPLC
      using a reversed-phase column. NMR and mass spectroscopy studies indicated that
      peak F2 (obtained from peak 4) contained adenosine and cytidine. Deamination of
      peak F2 with adenosine deaminase almost completely abolished its anti-platelet
      activity, confirming the presence of adenosine in this fraction. In comparison,
      deamination of peak-4 resulted in only partial loss of inhibitory activity while
      the activity of peak-3 remained unaffected. These results indicate that tomatoes
      contain anti-platelet compounds in addition to adenosine. Unlike aspirin, the
      tomato-derived compounds inhibit thrombin-induced platelet aggregation. All these
      data indicate that tomato contains very potent anti-platelet components, and
      consuming tomatoes might be beneficial both as a preventive and therapeutic
      regime for cardiovascular disease.

PMID- 11454257
TI  - Two distinct mechanisms are involved in stent thrombosis under flow conditions.
AB  - The mechanism of stent thrombosis was evaluated by a flow chamber model. A Palmaz
      Schatz stent was placed on glass surfaces coated with type I collagen in a
      parallel-plate flow chamber. Platelets were rendered fluorescent with mepacrine
      and whole blood was perfused through the chamber. Platelet thrombi formed around
      the implanted stents were continuously recorded by epi-fluorescent video
      microscopy. Platelet thrombi appeared on the collagen surface within a few
      minutes in the absence of function blocking monoclonal antibodies. Antibody
      blocking vWF interaction with GP Ib alpha completely inhibited the platelet
      thrombi around the stent, but had no effect on platelet thrombus formation in the
      space between the stents and collagen, while both were inhibited by anti-GP
      IIb/IIIa. Our results suggest that two distinct mechanisms, one mediated by vWF
      interaction with GP Ib alpha occurring at high shear rates, and the other
      mediated exclusively by GP IIb/IIIa occurring at low shear rates, are involved in
      the process of platelet thrombus formation in the presence of stents.

PMID- 11454258
TI  - Impact of plasmapheresis on platelet hemostatic capacity in healthy voluntary
      blood donors detected by the platelet function analyzer PFA-100.
AB  - Previous flow cytometry studies showed that platelet activation may occur during
      cytapheresis, cardiopulmonary bypass and hemodialysis. The aim of this pilot
      study was to determine if the impact of plasmapheresis leads to alterations in
      platelet hemostatic capacity. Plasmapheresis was carried out in 30 volunteers
      using an Autopherese C (Baxter) and an MCS3p (Haemonetics). Blood samples were
      collected and analyzed immediately before and after plasmapheresis. As a result
      of the plasmapheresis on the Autopherese C, the mean closure time (CT) for
      collagen/epinephrine (Col/Epi) increased from 118.2 +/- 25.1 to 149.9 +/- 35.0 s
      and from 88.7 +/- 16.9 to 98.5 +/- 26.3 s for collagen/ADP (Col/ADP),
      respectively. Seven subjects showed impaired CTs after plasmapheresis for
      Col/Epi. For Col/ADP, five subjects showed impaired CTs after apheresis.
      Statistical analysis (McNemar test) showed a significant difference before and
      after apheresis for Col/Epi (P = 0.024) but not for Col/ADP (P = 0.088). Similar
      results were shown for plasmapheresis carried out with the MCS3p. These findings
      show that plasmapheresis can cause an impairment of platelet function in healthy
      volunteers as measured by the PFA-100, an effect of so far unknown clinical
      significance.

PMID- 11454259
TI  - Platelet hyperreactivity after coronary artery bypass grafting: the possible
      relevance to glycoprotein polymorphisms. A preliminary report.
AB  - Coronary artery bypass grafting (CABG) surgery impairs platelet function and
      reactivity to a considerable extent. However, variability in the individual
      patients' responses makes any generalised statement uncertain. The observed
      variability is nowadays thought to relate to platelet glycoprotein polymorphisms.
      Our objective was to investigate the association between platelet reactivity and
      the restoration of platelet functional response to agonists during the period
      following cardiosurgical operation and some genetic polymorphisms of selected
      platelet membrane glycoproteins. Platelet reactivity was monitored in 32 IHD
      patients (56 +/- 8 years) subjected to CABG surgery by means of whole blood
      impedance aggregometry and concurrently using the platelet function analyser (PFA
      100 at four time intervals: prior to operation (A), 2 h after administration of
      protamine sulfate (B), 3 days after (C) and 7 days after CABG surgery (D). Three
      important findings were made. First, in all patients platelet reactivity became
      decreased 2 h postoperatively (aggregation with 20 microM ADP reduced by up to
      49%, P < 0.02) and vastly increased 7 days after CABG surgery (CT(CADP) reduced
      down to 87% of initial value, P < 0.05, ADP-induced aggregation enhanced up to
      167%, P < 0.001, and that with collagen up to 131% of the initial value, P <
      0.01). Second, the frequencies of the 'prothrombotic' phenotype variants of
      platelet membrane glycoproteins were higher in patients referred to as the
      carriers of more reactive platelets compared to those with less reactive
      platelets (GPIa (807)T-positive, 50 vs. 28%; GPIIIa Pl(A2)-positive, 27 vs. 21%;
      GPIb Met(145)-positive and GPIb VNTR B-positive, 13 vs. 0%. Lastly, the
      restoration in platelet hyperreactivity in CABG surgery patients was recorded
      more often in patients who underwent postoperative myocardial ischaemic
      episode(s), and was associated with significantly higher frequency of the
      'prothrombotic' allele (807)T of the collagen receptor glycoprotein Ia (GPIa) in
      these subjects (83 vs. 61%). In conclusion, in patients with ischaemic episodes
      after CABG, we demonstrated a fast postoperative restoration of haemostatic
      capacity and evidence of platelet hyperreactivity at 7 days after CABG surgery.
      The platelet hyperfunction seems to relate to the occurrence of platelet
      glycoprotein polymorphisms GPIa(807)C/T and GPIIIa PlA(1/A2) and may be important
      in predicting postoperative vascular complications in CABG patients.

PMID- 11454260
TI  - Effects of autologous fresh platelet concentrate on haemostasis in cardiac
      reoperations.
AB  - The aim of this study was to determine whether autologous fresh platelet
      concentrate (PC) significantly improves haemostasis in cardiac reoperations
      compared with autologous fresh whole blood (WB). Forty-eight patients who had
      elective cardiac reoperations with a low-dose aprotinin priming regimen were
      divided into two groups. The amount of allogeneic blood transfusion was less in
      patients who were harvested 15 units of PC (Group PC; n = 24) before
      cardiopulmonary bypass (CPB) than patients who were harvested 400 ml of WB (Group
      WB; n = 24). The amount of mediastinal drainage for 12 h in intensive care units
      were significantly reduced in Group PC compared with Group WB (435 +/- 273 ml in
      Group PC versus 909 +/- 209 ml in Group WB; P < 0.001). Platelet count and
      collagen-induced whole blood platelet aggregation increased significantly higher
      in Group PC than Group WB after reinfusion. In conclusion, autologous fresh PC
      improved haemostasis compared with autologous fresh whole blood in cardiac
      reoperations with a low-dose aprotinin priming regimen.

PMID- 11454262
TI  - Are we meeting the psychological needs of Black African HIV-positive individuals
      in London? Controlled study of referrals to a psychological medicine unit.
AB  - The changing pattern of HIV infection in the UK includes an increase in the
      number of infections acquired as a result of heterosexual contact and Black
      African individuals represent a sizeable proportion of those affected. In most UK
      centres for the treatment of HIV infection, clinicians have limited experience in
      caring for Black African patients, and there is a dearth of information about the
      recognition and management of mental health problems in this patient group. In
      this investigation the proportion of Black African individuals looked after in a
      large centre for the care of HIV infection in London was compared with the
      proportion of such patients referred for specialist mental health help, the
      results revealing that Black Africans were almost three times less likely to be
      referred for specialist mental health care. A case control investigation of those
      referred to mental health services showed that Black Africans were more likely to
      be suffering from AIDS at the time of referral, be referred for assessment of
      possible organic brain disease, and more likely to be found to be suffering from
      major depression or organic brain disease. Reasons for the lesser likelihood of
      referral to the mental health service are considered, including the possible
      failure of staff to recognize psychological morbidity in Black Africans, or
      reluctance and fear on the part of patients to be referred to services that may
      be perceived as threatening.

PMID- 11454263
TI  - The involvement of people living with HIV/AIDS in community-based organizations:
      contributions and constraints.
AB  - An important feature of the social and organizational response to the HIV
      epidemic has been that many people living with HIV/AIDS have demanded to have a
      say in the development of policies and the delivery of services. Surprisingly
      little attention has been paid in the literature to this involvement. This paper
      is based on a participatory action research project that involved 70 people with
      HIV/AIDS in 15 focus group discussions. Findings from the study show the
      complexities of translating organizational commitments to involve people with
      HIV/AIDS into practice. This paper outlines the organizational contributions of
      people with HIV, and examines the difficulties and obstacles to their meaningful
      involvement. The paper concludes with a discussion of the challenges of user
      empowerment and with recommendations for policy and practice.

PMID- 11454264
TI  - AIDS-related discrimination in the workplace--the results of two evaluative
      surveys carried out during a three-year period in Hong Kong.
AB  - Two longitudinal surveys were carried out in 1996 and 1999 aimed at describing
      the situations of AIDS-related discrimination in the workplace and evaluating the
      effectiveness of some social interventions against discrimination towards HIV
      positive employees. Two hundred and ninety-nine and 212 companies completed a
      questionnaire in 1996 and 1999, respectively. The results are mixed. Although
      most of the sampled companies had no HIV/AIDS-related policy, their awareness of
      related legislation increased over the three-year period. Over the three-year
      study period, more companies indicated they would disclose information of their
      HIV-positive employees if known to the company; however, fewer companies
      indicated they would dismiss an employee because of his or her HIV-positive
      status. Only a few companies indicated that they would provide counselling and
      support to an HIV-positive employee.

PMID- 11454265
TI  - Promoting the positive: responses to stigma and discrimination in Southeast Asia.
AB  - Pervasive stigma has surrounded HIV/AIDS since the beginning of the pandemic. In
      Southeast Asia, as elsewhere, it has been accompanied by discrimination,
      affecting transmission patterns and access to care and support. Beginning with
      definitions of stigma and discrimination as they relate to HIV/AIDS, this paper
      outlines the contexts of discrimination experienced in the region and reviews
      local community-based interventions that have worked to reduce negative
      attitudes. The evidence presented comes primarily from unpublished literature and
      anecdotal evidence gained through interviews with project staff throughout the
      region. Although the activities represent initiatives in a number of countries
      and contexts of discrimination, they nonetheless share certain components which
      are highlighted. What these characteristics have in common is an emphasis on
      process, indicating that reducing community-level discrimination can be
      integrated into any approach to HIV/AIDS.

PMID- 11454266
TI  - So much for keeping secrets: the importance of considering patients' perspectives
      on maintaining confidentiality.
AB  - Little data are available from patients' perspectives regarding the maintenance
      of confidentiality by care providers. Such data may be useful in determining the
      importance of confidentiality to patients and in developing appropriate policies
      and procedures regarding confidentiality. Three focus groups were conducted with
      support groups of rural HIV-positive patients. Text was coded inductively and
      analyzed with software designed for qualitative analysis. Participants perceived
      breaches of confidentiality in hospitals, clinics and health departments that
      occurred by word of mouth, computers, facsimile and written materials. Patients
      included sharing stigmatizing medical information among medical providers without
      prior consent as a breach. They made decisions about where to seek care based on
      the degree of professionalism of medical staff (which included respecting
      confidentiality), clinic location or the level of security of the organization's
      computer network since they believed that computers increase information access.
      Finally, participants believed that medical personnel should be taught the
      importance of maintaining confidentiality and that those who violated
      confidentiality should be punished. Patients would like confidentiality policies
      that require providers to: (1) explain procedures for sharing information, (2)
      request patients' specific consent for access to their medical records, even
      among other providers, and (3) punish those who breach confidentiality.

PMID- 11454267
TI  - Outcomes of a health education intervention in a sample of patients infected by
      HIV, most of them injection drug users: possibilities and limitations.
AB  - We studied the receptivity of a population of HIV-infected patients to the
      development of a group educational intervention in order to enhance the adherence
      to therapy. We designed a group educational activity conducted by family
      physicians and directed to patients with HIV infection treated with
      antiretrovirals for at least six months. We conducted a randomized trial that
      compared two interventions: an educational intervention plus individual counsel
      or the last option alone. We studied their clinical situation, adherence to
      therapy and familial support. We offered 115 patients (66.9% injection drug users
      (IDUs), 69.6% males) the opportunity to be included in our trial, but 73.9% of
      them refused. No group with four or more participants was formed. Fifty-nine per
      cent refused to be included claiming personal reasons and 32.9% cited trouble in
      their jobs. There was a non-significant trend to accept in the case of women (p =
      0.19), patients with AIDS (p = 0.11) and non-adherent patients (p = 0.08). This
      trend was significant in the group of women with AIDS (p = 0.01) and non-adherent
      women (p = 0.05). We concluded that HIV-infected patients, mainly IDUs, are not
      receptive to group educational programmes. The design of future interventions
      must take into account the patients' characteristics.

PMID- 11454268
TI  - Father-child contact in inner-city African American families with maternal HIV
      infection.
AB  - This study examines father-child contact in inner-city African American families
      with maternal HIV infection. Participants were 246 African American women, 40% of
      whom are infected with HIV, and one of their non-infected children. Children from
      non-infected families were more likely to have fathers who are alive and who are
      living in the home. In addition, regardless of whether or not the father lived in
      the home, these children had more frequent father contact than children from
      families with maternal HIV infection. Explanations and implications of the
      findings are discussed.

PMID- 11454269
TI  - Outcomes of HIV/AIDS case management in New York.
AB  - The purpose of this study was to examine HIV case management (CM) outcomes in New
      York State. The results presented here are part of a larger study that explored:
      client needs identified during CM, success in arranging needs, other case
      managers used by the client, coordination between multiple case managers, client
      satisfaction with CM, and the correlation between health care costs and CM. This
      paper focuses on the linkage of clients with services. Twenty-eight agencies and
      588 clients participated in the study. Each client's chart was reviewed; clients
      and case managers were interviewed. Almost 9,000 client needs were identified;
      79.3% of these needs were for services. Over 72% of needed services were arranged
      for clients. However, of the services arranged, 12.9% were never utilized.
      Success in arranging services did not vary based on client demographics; client
      utilization of services, once arranged, varied based on only one demographic
      factor (clients who lived outside of New York City had higher utilization rates
      than those who lived in the city, p < or = 0.05). Services provided directly by
      the CM agency were arranged and utilized more frequently than services provided
      by another agency (p < or = 0.05). Medical needs were arranged and utilized at a
      higher rate-and legal needs at a lower rate-than other services, regardless of
      where the service was provided (p < or = 0.05). On average it took 2.3 months to
      arrange a service; however it took less time to arrange medical services and more
      time to arrange legal services (p < or = 0.05). Females, individuals whose mode
      of HIV transmission was heterosexual contact, clients whose children were living
      with them, the inadequately housed, and those without a high school diploma had
      significantly more needs than other clients (p < or = 0.05). Our study supports
      CM models that provide intensive services to women with children; the provision
      of multiple services, in addition to CM, within a single agency; and the need for
      case manager training on how to work with clients to increase service
      utilization.

PMID- 11454270
TI  - Motivational interviewing for HIV risk reduction among gay men in commercial and
      public sex settings.
AB  - The present paper addresses the feasibility of combining motivational
      interviewing and cognitive interventions to HIV risk reduction in commercial
      venues and public sex environments (PSEs). The logic for these two approaches is
      considered and an intervention combining key elements of the two is presented.
      The intervention uses a questionnaire format to encourage individuals to compare
      their desired versus actual behaviour (i.e. chosen personal risk reduction
      strategy versus 'slip-ups'/unwanted risk taking), and to recognize their risk
      related cognitions. High-risk individuals are identified, and health-focused
      conversations developed from the brief schedule. The structure and key design
      issues in the development of a feasible, acceptable and evidence-based tool are
      reviewed. The limitations of more complex, focused interventions in the context
      of commercial and PSE settings are discussed.

PMID- 11454271
TI  - HIV risk behaviour among men who have sex with men in public sex environments: an
      ecological evaluation.
AB  - Men who have sex with men (MSM) in public sex environments (PSE) may be at high
      risk for HIV/AIDS. The majority of research on HIV risk behaviour among MSM has
      been conducted in open access venues more likely to be linked to networks that
      openly endorse preventive messages and safer sex norms. This study investigated
      risk practices among MSM in a PSE in order to develop effective prevention
      intervention strategies. Three outreach workers with previous MSM prevention
      experience trained in ethnographic and fieldwork observation techniques provided
      direct observation data. Seventy-seven observations, each lasting a minimum of
      two hours, were conducted over a five-month period at three city public parks. Of
      614 men observed, over 250 exhibited activities and behaviours related to, or
      potentially related, to HIV-risk relevant sexual behaviour. Direct sexual contact
      between two or more men was observed 19 times, while men entering or leaving a
      sex area of the park was observed 66 times. Outreach workers were able to
      interact directly with 72 MSM, primarily discussing safer sex strategies. Sexual
      encounters occurred in more open areas of the PSE with partners migrating to
      secluded areas for intense and sexual interactions. Future prevention
      interventions will need to be tailored, and targeted, to specific sexual exchange
      access points in PSE.

PMID- 11454272
TI  - Reflection and dialogue for HIV prevention among young gay men.
AB  - Considerable interest has been expressed in young gay men's enhanced
      vulnerability to HIV-related risk. Relatively little research has, however, been
      conducted into the circumstances in which risk may be greatest and the strategies
      young gay men can use to reduce their vulnerability. This paper reports on
      findings from a recent exploratory in-depth study conducted in Norway. Twenty
      young gay men participated in repeated dialogic and reflective interviews in
      which situations of real and potential risk were discussed. Central among the
      factors enhancing vulnerability were found also to be general social codes such
      as configurations of 'reciprocity', as well as context-specific factors and
      individual biographic variables. A mode of intervention is described that seeks
      to empower young men more fully in sexual communication and negotiation. Such an
      approach has been operationalized in 'man-to-man dialogues' facilitated by
      members of the Norwegian Gay Health Committee.

PMID- 11454273
TI  - Substance use and unsafe sex amongst homosexual men in Edinburgh.
AB  - A self-reported behaviour survey using an anonymous critical incident based
      questionnaire was administered by trained interviewers in 1998. Five hundred and
      thirty-one homosexual and bisexual men were recruited from gay bars, clubs,
      cafes, a sauna and 'cruising ground' in central Edinburgh. The use of alcohol and
      recreational drugs and details of sexual activity over the preceding three months
      and at the last sexual encounter were recorded. Unsafe sex was defined as anal
      sex without the use of a condom with a partner of unknown or different HIV
      status. Safer sex was defined as all other types of sex, including anal sex with
      a condom and anal sex without a condom with a partner whose HIV status was known
      to be the same. Of the questionnaires completed, 506 were suitable for analysis;
      29 men (6.1%) reported anal sex with a partner of unknown or different HIV status
      without a condom ('unsafe sex') during their last sexual encounter. A total of 53
      men (10.5%) could recall an episode of unsafe sex within the last three months.
      Men who had used marijuana or inhaled nitrites ('poppers') less than two hours
      before sex, or whose sexual partners had done so, were more likely to have unsafe
      sex than those who had not. Although alcohol use was more likely before sex with
      casual partners, the use of alcohol less than 2 hours before sex was not
      associated with sex being unsafe.

PMID- 11454275
TI  - World Health Organization Global AIDS Statistics.

PMID- 11454276
TI  - Effects of NF-kappaB1 (p50) targeted gene disruption on ionizing radiation
      induced NF-kappaB activation and TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA
      expression in vivo.
AB  - PURPOSE: To investigate the role of the NF-kappaB1 (p50) gene in ionizing
      radiation (IR)-induced NF-kappaB activation and TNFalpha, IL-1alpha, IL-1beta and
      IL-6 mRNA expression in vivo. MATERIALS AND METHODS: NF-kappaB activation was
      analysed by the gel shift/supershift assay and the levels of TNFalpha, IL-1alpha,
      IL-1beta and IL-6 mRNA were measured using RNase protection assay (RPA). Various
      tissues from BALB/c, B6,129P-Nfkb1 (NF-kappaB1 or p50 gene knockout, p50(-/-))
      and B6,129PF2 (wild-type, p50(+/+)) mice were analysed before or after exposure
      to a lethal dose (8.5 Gy) of total-body gamma-irradiation. RESULTS: Exposure of
      BALB/c mice to total-body IR selectively activated NF-kappaB in the spleen,
      mesenteric lymph nodes (LN) and bone marrow (BM). Gel supershift assay using
      polyclonal antibodies against NF-kappaB p50, p65 or c-Rel protein revealed that
      the NF-kappaB p50 subunit is a critical component of the NF-kappaB complexes
      activated by IR in vivo. Discretely augmented TNFalpha, IL-1alpha, IL-1beta and
      IL-6 mRNA expression was found in the spleen, LN and BM after BALB/c mice
      received IR. However, mice lacking the p50 gene (p50(-/-)) showed a significant
      reduction in IR-induced activation of NF-kappaB and increases in TNFalpha, IL
      1alpha, IL-1beta and IL-6 mRNA expression, as compared with that of wild-type
      mice (p50(+/+)). CONCLUSIONS: The NF-kappaB p50 subunit is a critical component
      of the NF-kappaB complexes activated by IR and it plays an important role in
      mediating IR-induced TNFalpha, IL-1alpha, IL-1beta and IL-6 mRNA expression in
      vivo.

PMID- 11454277
TI  - Investigation of G2-phase chromosomal radiosensitivity in hereditary non
      polyposis colorectal cancer cells.
AB  - PURPOSE: To investigate whether cells from hereditary nonpolyposis colorectal
      cancer (HNPCC) patients, a genetic condition characterized by constitutional
      mutations in DNA mismatch repair genes and associated with predisposition to
      colorectal carcinoma (CRC), could present a higher G2 chromosomal
      radiosensitivity. It is generally hypothesized that cancer predisposition in
      HNPCC is associated with the loss of the wild-type allele in somatic cells,
      resulting in defective DNA mismatch repair but, to date, no data on G2
      radiosensitivity have been reported for HNPCC. MATERIALS AND METHODS:
      Lymphoblastoid cell lines derived from six HNPCC patients heterozygous for MLH1,
      one HNPCC patient carrying a mutant MSH2 allele and three healthy controls were
      treated with 50 cGy of X-rays and sampled at various harvesting times, monitoring
      cell-cycle progression by 5-bromo-2-deoxyuridine (BrdUrd) incorporation in order
      to analyse chromosomal damage in the homogeneous G2 population. RESULTS: There
      were no differences between lymphoblasts derived from patients in the frequency
      of G2 chromosomal aberrations induced by X-rays when compared with control cell
      lines. However, despite the absence of G2 radiosensitivity in HNPCC cells,
      lymphoblasts from patients heterozygous for MLH1 mutations showed a higher
      induction of chromatid exchanges. CONCLUSIONS: The observed possible incorrect
      rejoining of double-strand breaks in MLH1 heterozygotes would be an additional
      and important factor contributing to loss of heterozygosity in HNPCC patients.

PMID- 11454278
TI  - Relationship between radiation-induced aberrations in individual chromosomes and
      their DNA content: effects of interaction distance.
AB  - PURPOSE: To study the effect of the interaction distance on the frequency of
      inter- and intrachromosome exchanges in individual chromosomes with respect to
      their DNA content. Assumptions: Chromosome exchanges are formed by misrejoining
      of two DNA double-strand breaks (DSB) induced within an interaction distance, d.
      It is assumed that chromosomes in G(0)/G(1) phase of the cell cycle occupy a
      spherical domain in a cell nucleus, with no spatial overlap between individual
      chromosome domains. RESULTS: Formulae are derived for the probability of
      formation of inter-, as well as intra-, chromosome exchanges relating to the DNA
      content of the chromosome for a given interaction distance. For interaction
      distances <1 microm, the relative frequency of interchromosome exchanges
      predicted by the present model is similar to that by Cigarran et al. (1998) based
      on the assumption that the probability of interchromosome exchanges is
      proportional to the "surface area" of the chromosome territory. The "surface
      area" assumption is shown to be a limiting case of d-->0 in the present model.
      The present model also predicts that the probability of intrachromosome exchanges
      occurring in individual chromosomes is proportional to their DNA content with
      correction terms. CONCLUSION: When the interaction distance is small, the
      "surface area" distribution for chromosome participation in interchromosome
      exchanges has been expected. However, the present model shows that for the
      interaction distance as large as 1 microm, the predicted probability of
      interchromosome exchange formation is still close to the surface area
      distribution. Therefore, this distribution does not necessarily rule out the
      formation of complex chromosomal aberrations by long-range misrejoining of DSB.

PMID- 11454279
TI  - Fluorescence in situ hybridization of metaphase chromosomes in suspension.
AB  - PURPOSE: To describe a new method for FISH analysis of metaphase chromosomes in
      suspension. MATERIALS AND METHODS: Metaphase chromosomes in suspension were
      isolated from a Chinese hamster human hybrid cell line, 314-2 (1) Y, and a human
      cell line, GM 130B. During suspension hybridization, specific chromosomes were
      labeled from these two cell lines using either biotin-labeled human genomic DNA,
      a directly labeled human pancentromere DNA probe or a chromosome #1 locus
      specific probe. RESULTS: The method allows, for the first time, recovery of large
      numbers of isolated individual hybridized chromosomes with good morphology for
      both human x hamster hybrid and human cell lines. The results showed that 46-73%
      of the starting number of total chromosomes can be recovered after a FISH in
      suspension procedure. The well-preserved morphology of hybridized metaphase
      chromosomes allowed (1) rapid detection of individual human and hamster
      chromosome aberrations, (2) rapid counting of the painted human chromosomes and
      (3) fast, clear detection of chromosome region-specific probes. This method
      offers a new tool to assay chromosomes and DNA: it offers the possibility to
      develop new techniques for sorting chromosomes based on FISH signals, for early
      detection and screening of genetic diseases and for bulk measurement of both
      balanced or unbalanced chromosomal exchanges and rearrangements. CONCLUSION: The
      potential of the method described should facilitate fast, sensitive population
      monitoring, and increase sensitivity of the measurements in chromosome-based
      biodosimetry.

PMID- 11454280
TI  - Biodosimetry using chromosomal translocations measured by FISH in a population
      chronically exposed to low dose-rate 60Co gamma-irradiation.
AB  - PURPOSE: To evaluate the cumulative gamma-radiation personal exposure by
      analysing lymphocyte chromosome translocations using FISH painting and to compare
      FISH-derived biodoses with those derived from retrospective physical dose
      reconstruction in residents receiving chronic low dose-rate gamma-irradiation
      while living in radio-contaminated buildings. MATERIALS AND METHODS: Chromosome
      translocation frequencies were evaluated by scoring 933 to 3077 metaphases under
      fluorescence microscope for each of the five male and four female exposed
      individuals after they had relocated from the radioactive environment for 34-82
      months. FISH painting was conducted using kits of whole-chromosome probes for
      chromosomes 1, 2 and 4 in orange and 3, 5 and 6 in green and counter-stained with
      4',6-diamidino-2-phenylindole (DAPI). The retrospective dose estimation termed
      Taiwan Cumulative Dose (TCD) was conducted by assessment using detailed
      information of historical exposure and the environmental radioactivity for each
      apartment during previous residency. RESULTS: A total of 20 244 well-prepared
      metaphases were scored. Biodoses were calculated from the translocation
      frequencies and physical doses were estimated from detail questionnaires for each
      individual. The translocation frequencies measured ranged from 2.2x10(-3) to
      26.8x10(-3) translocations per cell and the dose equivalent from 52.2 to
      992.2mSv. A good correlation was observed between the physical and biodoses. A
      plot of TCD against FISH-derived doses produced D(fish) =0.65 D(TCD), when fitted
      by a linear model, and D(fish) = 0.53 D(TCD)+ 1.26x10(-4 ) D(2)(TCD), when fitted
      with a linear-quadratic model. Given the scatter in the data and the extremely
      small quadratic dose contribution, neither model could be ruled out. CONCLUSION:
      Chromosome translocations provide a valid method of dose estimation in extremely
      protracted low dose-rate gamma-radiation exposure. Validation of the TCD method
      by FISH-measured translocations supports the use of TCD for epidemiological
      studies.

PMID- 11454281
TI  - In utero haemopoietic sensitivity to alpha, beta or X-irradiation in CBA/H mice.
AB  - PURPOSE: To assess in utero sensitivity to x-rays, alpha-emissions from plutonium
      239 and beta-emissions from tritium in terms of induction of chromosomal
      aberrations in bone marrow cells. MATERIALS AND METHODS: CBA/H mice were exposed
      to a single dose of X-rays (0.5Gy) on either day 7 or day 14 of pregnancy or
      given (239)Pu (100 kBq kg(-1)) by intraperitoneal injection on either day 6 or
      day 13. Tritium was administered to mice throughout pregnancy as either tritiated
      water, ad libitum in drinking water (total intake averaged 130 MBq), or as
      homogenized tritiated cress, administered by gastric intubation (total 60 MBq).
      Irradiated and unexposed control mice and their offspring were sacrificed at 2-8
      weeks after birth. Direct metaphase preparations from femoral bone marrow cells
      from mothers and offspring were used for G-band analysis. RESULTS: The incidence
      of stable aberrations was significantly and similarly increased in neonatal and
      maternal marrow samples after exposure to X-rays, (239)Pu or (3)H. The estimated
      average bone absorbed doses from (239)Pu in pregnant females were similar to the
      X-ray dose of 0.5 Gy, suggesting a low RBE for alpha-irradiation in adults. The
      similar levels of damage observed in neonates after X-irradiation and 239Pu
      exposure are indicative of greater in utero sensitivity to alpha-irradiation
      since the overall estimated in utero alpha-particle doses to haemopoietic tissue
      were much lower. In utero doses from (3)H and corresponding maternal doses were
      around 0.5Gy, showing no evidence of greater in utero sensitivity, no significant
      difference between the effects of the two forms of tritium, and were consistent
      with an RBE value of 1-2. CONCLUSIONS: Comparison of stable aberration yields in
      haemopoietic cells suggests a greater sensitivity to alpha-particles from (239)Pu
      than X-rays or beta-particles from (3)H for irradiation in utero but a low RBE
      value in adults.

PMID- 11454282
TI  - Protocol for X-ray dosimetry in radiobiology.
AB  - PURPOSE: To harmonize X-ray dosimetry in radiobiology to allow a direct
      comparison of radiobiological studies performed at institutes cooperating within
      the framework of the European Late Effects Project Group (EULEP). MATERIALS AND
      METHODS: The 1985 EULEP protocol for X-ray dosimetry and exposure arrangements
      employed for studies of late somatic effects in mammals required serious
      revision, e.g. due to the replacement of calibration of dosemeters in terms of
      exposure by calibration in terms of air kerma free-in-air. An action group
      established by EULEP and the European Radiation Dosimetry Group (EURADOS) updated
      the 1985 protocol. RESULTS: The new EULEP-EURADOS protocol for X-ray dosimetry in
      radiobiology including the code of practice for irradiation of small animals and
      related dosimetry. The present protocol includes the changes in calibration
      procedures and dosimetric concepts for irradiation with medium energy X-rays
      since 1985. Accuracy and precision are replaced by the concept of combined
      (standard) uncertainty. The revised supplements provide more detailed background
      information. New appendices contain definitions of general terms used for
      measurements and mathematical expressions of the relative variances. CONCLUSION:
      Adherence to the present protocol will result in improved dosimetry and
      facilitates the comparison of results of radiobiological experiments obtained at
      different institutes.

PMID- 11454285
TI  - Are there fitness advantages in being a rewardless orchid? Reward supplementation
      experiments with Barlia robertiana.
AB  - The Orchidaceae characteristically contain a very large number of species that
      attract pollinators but do not offer them any form of reward in return for
      visitation. Such a strategy is highly unusual in the plant kingdom. We conducted
      experiments in order to manipulate the reward strategy of the rewardless bumble
      bee-pollinated orchid Barlia robertiana by adding sucrose solution to
      inflorescences. We found that supplementation decreased the probability of a
      pollinator removing pollinia by approximately ten times. Despite pollinators
      visiting many more flowers per inflorescence on supplemented plants, eight times
      fewer pollinia were removed from supplemented inflorescences during each visit.
      Pollinia deposition patterns were not significantly affected by supplementation
      and no geitonogamous deposition was recorded. In populations where inflorescences
      were supplemented for 20 days, pollinia removal was reduced by over half for
      supplemented inflorescences, whereas fruit set was unmodified by supplementation.
      We conclude that rewardlessness would increase total seed paternity, but not
      change either total seed maternity or the probability that offspring were
      outcrossed in this species. To the authors' knowledge this is the first time that
      there has been an unequivocal experimental demonstration of an evolutionary
      advantage for rewardlessness in the Orchidaceae.

PMID- 11454286
TI  - Lift generation by the avian tail.
AB  - Variation with tail spread of the lift generated by a bird tail was measured on
      mounted, frozen European starlings (Sturnus vulgaris) in a wind tunnel at a
      typical air speed and body and tail angle of attack in order to test predictions
      of existing aerodynamic theories modelling tail lift. Measured lift at all but
      the lowest tail spread angles was significantly lower than the predictions of
      slender wing, leading edge vortex and lifting line models of lift production.
      Instead, the tail lift coefficient based on tail area was independent of tail
      spread, tail aspect ratio and maximum tail span. Theoretical models do not
      predict bird tail lift reliably and, when applied to tail morphology, may
      underestimate the aerodynamic optimum tail feather length. Flow visualization
      experiments reveal that an isolated tail generates leading edge vortices as
      expected for a low-aspect ratio delta wing, but that in the intact bird body-tail
      interactions are critical in determining tail aerodynamics: lifting vortices shed
      from the body interact with the tail and degrade tail lift compared with that of
      an isolated tail.

PMID- 11454287
TI  - Males of social insects can prevent queens from multiple mating.
AB  - During copulation, males of Bombus terrestris fill the queen's sexual tract with
      a mating plug after transferring their sperm. The sticky secretion is produced by
      the male's accessory glands and disappears within a couple of days. Experiments
      now show that the primary function of the plug is to reduce the subsequent mating
      probability of the queen. The plug is not efficient in preventing sperm migration
      into the spermatheca. Due to its low energetic value, the plug is also unlikely
      to serve as a nuptial gift. This type of male interference with female mating
      propensity has so far not been found in social insects. This finding could, at
      least tentatively, explain why females of B. terrestris may not be able to take
      advantage of the demonstrated benefits of multiple mating. Furthermore, such male
      interference could be a more general phenomenon in social insects, with obvious
      ramifications for the evolution of polyandry in this group.

PMID- 11454288
TI  - Offspring body condition and immunocompetence are negatively affected by high
      breeding densities in a colonial seabird: a multiscale approach.
AB  - Why avian colonies vary in size and how food competition among nearby colonies
      affects offspring quality are still not completely understood. We simultaneously
      examined the effects of four scales of breeding density on two measures of
      offspring viability (body condition and T-cell-mediated immunity) in the colonial
      Magellanic penguin. Body condition of fledglings was inversely correlated with
      breeding density within 100 m(2) of nests, and decreased with increasing numbers
      of breeding pairs competing within the parental foraging ranges (100 km),
      probably as a result of density-dependent food depletion. The T-cell-mediated
      immune response was positively correlated with body condition, reflecting, to
      some extent, the previous breeding-density effects, and was negatively correlated
      with colony size, which may be related to social stress. However, given the
      effect of protein intake on cell immunity, this result could also indicate a thus
      far neglected cost of coloniality, namely the consumption of low-protein food to
      compensate for the depletion of optimal prey. These results were not influenced
      by other traits, nor by the current exposure of birds to parasites and diseases,
      as measured by serological variables. Since body condition and the T-cell
      mediated immune response of fledgling birds are indicators of their survival and
      recruitment prospects, the costs we have identified can explain variability in
      colony size in relation to food competition with surrounding colonies, as well as
      the skewed distribution toward small colonies in this species.

PMID- 11454289
TI  - Inter- and intraspecific trait compensation of defence mechanisms in freshwater
      snails.
AB  - Trait compensation occurs when mechanically independent adaptations are
      negatively correlated. Here, we report the first study to demonstrate trait
      compensation in predator-defence adaptations across several species. Freshwater
      pulmonate snails exposed experimentally to predation chemical cues from fishes
      and crushed conspecifics showed clear interspecific differences in their
      behavioural avoidance responses, which were negatively correlated with shell
      crush resistance. The type of avoidance response varied between species: thin
      shelled species (Lymnaea stagnalis and Physa fontinalis) moved to the water-line
      or out of the water, while those with thick shells moved under cover or showed a
      mixed response. There were also intraspecific size-linked differences, with an
      ontogenetic increase in shell strength accompanied by a decrease in behavioural
      avoidance. Such trait compensation in response to predation has important
      implications for interspecific interactions and food-web dynamics.

PMID- 11454290
TI  - Interaction between directional epistasis and average mutational effects.
AB  - We investigate the relationship between the average fitness decay due to single
      mutations and the strength of epistatic interactions in genetic sequences. We
      observe that epistatic interactions between mutations are correlated to the
      average fitness decay, both in RNA secondary structure prediction as well as in
      digital organisms replicating in silico. This correlation implies that, during
      adaptation, epistasis and average mutational effect cannot be optimized
      independently. In experiments with RNA sequences evolving on a neutral network,
      the selective pressure to decrease the mutational load then leads to a reduction
      in the amount of sequences with strong antagonistic interactions between
      deleterious mutations in the population.

PMID- 11454291
TI  - Reversing insect adaptation to transgenic insecticidal plants.
AB  - The refuge-high-dose strategy for delaying insect adaptation to transgenic plants
      produces non-transgenic plants that enable survival of susceptible individuals.
      Previous theoretical work has suggested three requirements for success of the
      refuge-high-dose strategy: a low initial frequency of the resistance allele,
      extensive mating between resistant and susceptible adults and recessive
      inheritance of resistance. In order to understand an observed decrease in
      resistance frequency and improve the potential for managing resistance better, we
      used analytical and simulation models for exploring the conditions that prevent
      or reverse the evolution of resistance, even when resistance is not rare
      initially. Assuming random mating and recessive or nearly recessive inheritance
      of resistance, the factors favouring reversal of resistance are non-recessive
      costs of resistance, low initial resistance allele frequency, large refuges,
      incomplete resistance and density-independent population growth in refuges.

PMID- 11454292
TI  - Trophic status drives interannual variability in nesting numbers of marine
      turtles.
AB  - Large annual fluctuations are seen in breeding numbers in many populations of non
      annual breeders. We examined the interannual variation in nesting numbers of
      populations of green (Chelonia mydas) (n = 16 populations), loggerhead (Caretta
      caretta) (n = 10 populations), leatherback (Dermochelys coriacea) (n = 9
      populations) and hawksbill turtles (Eretmochelys imbricata) (n = 10 populations).
      Interannual variation was greatest in the green turtle. When comparing green and
      loggerhead turtles nesting in Cyprus we found that green turtles were more likely
      to change the interval between laying seasons and showed greater variation in the
      number of clutches laid in a season. We suggest that these differences are driven
      by the varying trophic statuses of the different species. Green turtles are
      herbivorous, feeding on sea grasses and macro-algae, and this primary production
      will be more tightly coupled with prevailing environmental conditions than the
      carnivorous diet of the loggerhead turtle.

PMID- 11454293
TI  - Autumn tree colours as a handicap signal.
AB  - Many species of deciduous trees display striking colour changes in autumn. Here,
      we present a functional hypothesis: bright autumn coloration serves as an honest
      signal of defensive commitment against autumn colonizing insect pests. According
      to this hypothesis, individuals within a signalling species show variation in the
      expression of autumn coloration, with defensively committed trees producing a
      more intense display. Insects are expected to be averse to the brightest tree
      individuals and, hence, preferentially colonize the least defensive hosts. We
      predicted that tree species suffering greater insect damage would, on average,
      invest more in autumn-colour signalling than less troubled species. Here, we show
      that autumn coloration is stronger in species facing a high diversity of damaging
      specialist aphids. Aphids are likely to be an important group of signal receivers
      because they are choosy, damaging and use colour cues in host selection. In the
      light of further aspects of insect and tree biology, these results support the
      notion that bright autumn colours are expensive handicap signals revealing the
      defensive commitment of individual trees to autumn colonizing insect pests.

PMID- 11454294
TI  - Cleaner fish Labroides dimidiatus manipulate client reef fish by providing
      tactile stimulation.
AB  - The cleaner wrasse Labroides dimidiatus often touches 'client' reef fish dorsal
      fin areas with its pelvic and pectoral fins. The relative spatial positions of
      cleaner and client remain constant and the cleaner's head points away from the
      client's body. Therefore, this behaviour is not compatible with foraging and the
      removal of client ectoparasites. As clients seek such 'tactile stimulation', it
      can be classified as an interspecific socio-positive behaviour. Our field
      observations on 12 cleaners (observation time of 112h) suggest that cleaners use
      tactile stimulation in order to successfully (i) alter client decisions over how
      long to stay for an inspection, and (ii) stop clients from fleeing or aggressive
      chasing of the cleaner in response to a cleaner fish bite that made them jolt.
      Finally, predatory clients receive tactile stimulation more often than non
      predatory clients, which might be interpreted as an extra service that cleaners
      give to specific partners as pre-conflict management, as these partners would be
      particularly dangerous if they started a conflict. We therefore propose that
      cleaner fish use interspecific social strategies, which have so far been reported
      only from mammals, particularly primates.

PMID- 11454295
TI  - Temperature shock during development fails to increase the fluctuating asymmetry
      of a sexual trait in stalk-eyed flies.
AB  - The fluctuating asymmetry (FA) of bilateral traits is claimed to be a general
      indicator of environmental stress. Exaggerated sexual ornaments are thought to
      show elevated levels of FA and a greater response to stress than other traits.
      Previous work with stalk-eyed flies (Cyrtodiopsis dalmanni) has shown that the FA
      of the sexual trait (male eye stalks), wing length and wing width were unaffected
      by a continually applied food stress. Here we tested whether a transient stress
      (24-h heat shock at 31 degrees C during development) affected the FA of these
      traits. A second experiment tested the combined stresses of transient heat shock
      at 31 degrees C with continuous exposure to desiccation. In each experiment,
      temperature shock reduced the trait size, confirming that the treatments were
      stressful. However, stress had no effect on the FA of individual traits or the FA
      summed across all traits. Exposure to the combined stresses significantly
      elevated mortality and reduced trait size compared to the single-stress regime.
      However, FA did not differ significantly between flies from the two experiments.
      We found no evidence that FA in sexual and non-sexual traits reflects transient
      stress during the development of C. dalmanni.

PMID- 11454296
TI  - Microsatellite and mitochondrial DNA homogeneity among phenotypically diverse
      crossbill taxa in the UK.
AB  - Genetic differentiation within and between the three morphologically divergent
      crossbill species extant in the UK was assessed by comparison of allele
      frequencies at five unlinked microsatellite loci and DNA sequence variation
      across the mitochondrial control region. No significant differences in
      microsatellite allele frequency were found either between different populations
      of the same species or between the crossbill species themselves. A similar lack
      of genetic divergence was apparent from the mitochondrial sequence data. We
      resolved 33 different haplotypes, separated by low levels of sequence divergence
      (0-0.15%). Levels of divergence within and between species were not significantly
      different. Haplotypes formed a polyphyletic phylogeny, indicating that the
      crossbill species do not form genetically separate clades. Discordance between
      neutral DNA polymorphisms and adaptive morphological variation is discussed in
      relation to defining the systematic relationship between crossbill forms. If
      adaptive differences have arisen without a concomitant divergence in neutral DNA
      then attempting to define crossbill types from microsatellite and mitochondrial
      DNA without recourse to ecology and behaviour may be misleading.

PMID- 11454297
TI  - Conspecific reproductive success affects age of recruitment in a great cormorant,
      Phalacrocorax carbo sinensis, colony.
AB  - Few studies have addressed the proximate factors affecting the age at which
      individuals of long-lived bird species are recruited into the breeding
      population. We use capture-recapture analysis of resightings of 16 birth cohorts
      of colour-ringed great cormorants, Phalacrocorax carbo sinensis, in a Danish
      colony to assess the evidence for two hypotheses: conspecific attraction (earlier
      recruitment when the colony is large) and conspecific reproductive success
      (earlier recruitment following years of high breeding success). For both males
      and females, conspecific reproductive success was the most important covariate
      explaining the interannual variation in age of recruitment; colony size was also
      important for females. These covariates explained nearly 60% of the year-to-year
      variation for both sexes. The age of recruitment increased for cohorts born after
      1990, and this increase was correlated with a decline in breeding success in the
      colony; we interpret this as an indirect and delayed density-dependent effect.
      Females were recruited earlier than males (mean age of recruitment for cohorts
      born before 1990: 2.98 years versus 3.53 years); the most plausible reason for
      this is a skewed sex ratio in favour of males in the adult population.
      Recruitment of males may thus, to some extent, be constrained by the availability
      of females. This study provides the first evidence that conspecific reproductive
      success can affect the age at which individual birds start to breed.

PMID- 11454298
TI  - How Drosophila males make eggs: it is elemental.
AB  - Oogenesis in Drosophila requires a significant amount of phosphorus. Oocytes
      mature in follicles, each of which contains 15 highly polyploid,
      transcriptionally active chromosomes. We show that the demand for phosphorus is
      met in part from the male's ejaculate following mating. Females incorporate
      phosphorus-32 from radiolabelled males into their ovaries, specifically into
      their nucleic acids. Male-derived phosphorus is also present in significant
      amounts in mature oocytes. The mechanism by which phosphorus uptake from the
      female reproductive tract occurs must differ from that previously reported for
      radiolabelled carbon and hydrogen derived from ejaculatory proteins, as
      phosphorus uptake is observed in species not showing female incorporation of
      radiolabel derived from ejaculate proteins.

PMID- 11454299
TI  - Mitochondrial genomes of a bandicoot and a brushtail possum confirm the monophyly
      of australidelphian marsupials.
AB  - Recent molecular analyses suggest that the position of bandicoots is the major
      difficulty in determining the root of the tree of extant marsupials. To resolve
      this, we analyse mitochondrial genome sequences of a bandicoot (Isoodon
      macrourus) and a brushtail possum (Trichosurus vulpecula) together with the
      previously available marsupial mitochondrial genomes, the Virginia opossum
      (Didelphis virginiana) and the wallaroo (Macropus robustus). Analyses of
      mitochondrial protein-coding and RNA genes strongly support the bandicoot as
      sister to the wallaroo and the brushtail possum. This result, combined with other
      recent molecular analyses, confirms the monophyly of Australidelphia
      (Australasian marsupials plus Dromiciops from South America). Further, RY coding
      was found to nullify AGCT coding nucleotide composition bias.

PMID- 11454300
TI  - MUSTA--a general, efficient, automated method for multiple structure alignment
      and detection of common motifs: application to proteins.
AB  - Here we present an algorithm designed to carry out multiple structure alignment
      and to detect recurring substructural motifs. So far we have implemented it for
      comparison of protein structures. However, this general method is applicable to
      comparisons of RNA structures and to detection of a pharmacophore in a series of
      drug molecules. Further, its sequence order independence permits its application
      to detection of motifs on protein surfaces, interfaces, and binding/active sites.
      While there are many methods designed to carry out pairwise structure
      comparisons, there are only a handful geared toward the multiple structure
      alignment task. Most of these tackle multiple structure comparison as a
      collection of pairwise structure comparison tasks. The multiple structural
      alignment algorithm presented here automatically finds the largest common
      substructure (core) of atoms that appears in all the molecules in the ensemble.
      The detection of the core and the structural alignment are done simultaneously.
      The algorithm begins by finding small substructures that are common to all the
      proteins in the ensemble. One of the molecules is considered the reference; the
      others are the source molecules. The small substructures are stored in special
      arrays termed combinatorial buckets, which define sets of multistructural
      alignments from the source molecules that coincide with the same small set of
      reference atoms (C(alpha)-atoms here). These substructures are initial small
      fragments that have congruent copies in each of the proteins. The substructures
      are extended, through the processing of the combinatorial buckets, by clustering
      the superpositions (transformations). The method is very efficient.

PMID- 11454301
TI  - An efficient test for comparing sequence diversity between two populations.
AB  - We address the problem of comparing interindividual genomic sequence diversity
      between two populations. Although the methods are general, for concreteness we
      focus on comparing two human immunodeficiency virus (HIV) infected populations.
      From a viral isolate(s) taken from each individual in a sample of persons from
      each population, suppose one or multiple measurements are made on the genetic
      sequence of a coding region of HIV. Given a definition of genetic distance
      between sequences, the goal is to test if the distribution of interindividual
      distances differs between populations. If distances between all pairs of
      sequences within each group are used, then data-dependencies arising from the use
      of multiple sequences from individuals invalidates the use of a standard two
      sample test such as the t-test. Where this problem has been recognized, a typical
      solution has been to apply a standard test to a reduced dataset comprised of one
      sequence or a consensus sequence from each patient. Disadvantages of this
      procedure are that the conclusion of the test depends on the choice of utilized
      sequences, often an arbitrary decision, and exclusion of replicate sequences from
      the analysis may needlessly sacrifice statistical power. We present a new test
      free of these drawbacks, which is based on a statistic that linearly combines all
      possible standard test statistics calculated from independent sequence
      subsamples. We describe statistical power advantages of the test and illustrate
      its use by application to nucleotide sequence distances measured from HIV-1
      infected populations in southern Africa (GenBank accession numbers AF110959-
      AF110981) and North America/Europe. The test makes minimal assumptions, is
      maximally efficient and objective, and is broadly applicable.

PMID- 11454302
TI  - Multiplex sequencing by hybridization.
AB  - One of the limitations of classical sequencing by hybridization (SBH) is the
      inefficient use of probes in the "all k-mers" array. This limitation occurs due
      to the relatively short length (roughly the square root of C) of target that may
      be reconstructed by an array with C probes. We propose a new strategy, multiplex
      sequencing by hybridization, that greatly increases the efficiency of target
      reconstruction. In the typical multiplex SBH method, many different target
      sequences are simultaneously reconstructed (as compared to a single sequence in
      classic SBH). This is accomplished by pooling the target sequences and performing
      several hybridization experiments. This procedure makes more efficient use of
      probes so that the combined length of sequence reconstructed per DNA array
      increases significantly as compared to classical SBH.

PMID- 11454303
TI  - Determination of bias in the relative abundance of oligonucleotides in DNA
      sequences.
AB  - Different statistical measures of bias of oligonucleotide sequences in DNA
      sequences were compared, both by theoretical analysis and according to their
      abilities to predict the relative abundances of oligonucleotides in the genome of
      Escherichia coli. The expected frequency of an oligonucleotide calculated from a
      maximal order Markov model was shown to be a degenerate case of the expected
      frequency calculated from biases of all subwords arising when noncontiguous
      subwords exhibit no bias. Since (at least in E. coli) noncontiguous sequences
      exhibit significant bias, the total compositional bias approach is expected to
      represent biases in genomic sequences more faithfully than Markov approaches. In
      fact, the efficacy of statistics based on Markov analysis even at the highest
      order were inferior in predicting actual frequencies of oligonucleotides to
      methods that factored out biases of internal subwords with gaps. Using total
      compositional bias as a measure of relative abundance, tetranucleotide and
      hexanucleotide palindromes were found to be distributed differently from
      nonpalindromic sequences, with their means shifted somewhat towards
      underrepresentation. A subpopulation of palindromic hexanucleotides, however, was
      highly underrepresented, and this group consisted almost entirely of targets for
      Type II restriction enzymes found within strains of E. coli. Sites recognized by
      Type I endonucleases from related strains were not markedly biased, and with
      pentanucleotides, palindromic and nonpalindromic sequences had nearly identical
      distributions. The loss of restriction sites may be explained by the free
      transfer of plasmids encoding restriction enzymes and episodic selection for the
      presence of the enzymes.

PMID- 11454304
TI  - A sequence alignment algorithm with an arbitrary gap penalty function.
AB  - An algorithm for aligning biological sequences is presented that is an adaptation
      of the sequence generating function approach used in the statistical mechanics of
      biopolymers. This algorithm uses recursion relationships developed from a
      partition function formalism of alignment probabilities. It is implemented within
      a dynamic programming format that closely resembles the forward algorithm used in
      hidden Markov models (HMM). The algorithm aligns sequences or structures
      according to the statistically dominant alignment path and will be referred to as
      the SDP algorithm. An advantage of this method over previous ones is that it
      allows more complicated and physically realistic gap penalty functions to be
      incorporated into the algorithm in a facile manner. The performance of this
      algorithm in a case study of aligning the heavy and light chain from the variable
      region of an immunoglobulin is investigated.

PMID- 11454305
TI  - On relationship inference using gamete identity by descent data.
AB  - Related individuals are identical by descent (IBD) at a genetic locus if they
      share the same DNA material from a common ancestor. Continuous gamete IBD data
      consist of the lengths of (in order) IBD and non-IBD regions along the genomes
      for gametes segregating from two related individuals and can be used to
      distinguish different relationships. Under the assumption that the crossovers
      follow a Poisson process, we show that the exact calculation of the likelihood of
      a particular relationship for a given gamete IBD datum is tractable.
      Greatgrandparent--greatgrandchild and cousin relationships are used as examples
      to illustrate our methods.

PMID- 11454306
TI  - The foundations of cellular therapy: Barnes and Loutit, 1957.

PMID- 11454307
TI  - Treatment of murine leukaemia with x-rays and homologous bone marrow: II. 1957.

PMID- 11454308
TI  - Investigator profile: Richard J. O'Reilly interviewed by Glaser VP.

PMID- 11454309
TI  - Experimental culture conditions are critical for ex vivo expansion of
      hematopoietic cells.
AB  - The ex vivo expansion of hematopoietic stem cells (HSC) for clinical use is now
      recognized to be a feasible and very promising approach for hematotherapy.
      Expansion of specific HSC subsets is required for different clinical
      applications, for example, to increase the number of mature cells, to produce
      specific cells for adoptive therapy, or to increase the number of primitive stem
      cells available for engraftment. Although hematopoietic growth factors can play
      an important role in this setting, in this review we emphasize that other
      variables affect the outcome of stem and progenitor cell expansion. These
      variables include the serum supplement, the purity of CD34(+) cells, the initial
      cell concentration, and the duration of culture. It is also essential to define
      standard culture conditions for normal stem cells and to limit or prevent
      expansion of residual tumor cells. In clinical applications, determination of the
      hematopoietic value of the expanded population is mandatory. Thus, we have to
      demonstrate the expansion of primitive hematopoietic progenitor and stem cells,
      with maintenance of their hematopoietic potential as assessed by in vitro or in
      vivo assays. We draw attention to the challenges in the clinical application of
      ex vivo expansion. These include the establishment of well-defined experimental
      conditions and the determination of the hematopoietic value of the expanded
      grafts, whatever the graft source: bone marrow, mobilized peripheral blood, or
      cord blood. Future studies hopefully will optimize these procedures and allow not
      only expansion but engineering of defined cellular functions as HSCs grow under
      defined conditions.

PMID- 11454310
TI  - Severe hematopoietic alterations in vitro, in bone marrow transplant recipients
      who develop graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) is currently one of the major obstacles for
      successful allogeneic bone marrow transplantation (BMT). GVHD results from a
      complex set of interactions between donor T cells and a variety of target tissues
      from the host. To gain a better understanding of the biology of the human
      hematopoietic system in GVHD patients, in the present study we have determined
      the progenitor cell content in bone marrow (BM) samples from BMT recipients, with
      and without GVHD, and followed their growth kinetics in Dexter-type long-term
      marrow cultures (LTMC). We have also assessed some aspects regarding the
      composition of the hematopoietic microenvironment developed in vitro. As compared
      to normal subjects, BMT recipients showed decreased numbers of myeloid,
      erythroid, and multipotent progenitor cells. Interestingly, progenitor levels
      were significantly lower in GVHD patients (7% of the levels in normal marrow)
      than in those without GVHD (44% of the levels in normal marrow). When marrow
      cells from BMT recipients were cultured in LTMC, hematopoiesis was sustained at
      lower levels and for shorter periods of time, as compared to cultures from normal
      subjects. The hematopoietic deficiencies observed in this in vitro system were
      also more pronounced in GVHD patients. In terms of the microenvironment elements,
      reduced numbers of fibroblastic progenitors and adherent stromal cells were
      observed in BMT recipients, as compared to normal subjects, who showed 7 colony
      forming unit fibroblast (CFU-F)/10(5) marrow cells and 320,000 adherent cells in
      LTMC. Again, GVHD patients showed more severe deficiencies (0.16 CFU-F/10(5)
      marrow cells and 34,000 adherent cells in LTMC) than patients without GVHD (2 CFU
      F/10(5) marrow cells and 122,000 adherent cells in LTMC). Our results demonstrate
      that the hematopoietic system of BMT recipients is impaired, both in terms of its
      in vitro composition and function, and that these deficiencies are clearly more
      pronounced in patients with GVHD than in those without GVHD. Finally, although
      the evidence is still preliminary, our results also indicate that the severity of
      the hematopoietic alterations may be greater in acute GVHD than in chronic GVHD.

PMID- 11454311
TI  - Human cord cell hematopoiesis in three-dimensional nonwoven fibrous matrices: in
      vitro simulation of the marrow microenvironment.
AB  - Current hematopoietic culture systems mainly utilize two-dimensional devices with
      limited ability to promote self-renewal of early progenitors. In vivo-like three
      dimensional (3-D) culture environments might be conducive to regulating stem cell
      proliferation and differentiation similar to in vivo hematopoiesis. The few 3-D
      cultures reported in the literature either produced few progenitors or provided
      little information about microenvironment. In this study, we constructed a 3-D
      hematopoietic microenvironment composed of nonwoven matrix and human cord blood
      (CB) cells to simulate the marrow microenvironment and expand cord progenitors.
      Nonwoven polyethylene terephthalate (PET) fabric with defined microstructure was
      used as the 3-D scaffold and the PET surface was modified by hydrolysis to
      improve cell adhesion. Different cell organizations were formed in a 3-D matrix
      in a developmental manner, from individual cells and cells bridging between
      fibers to large cell aggregates. Both stromal and hematopoietic cells were
      distributed spatially within the scaffold. Compared to two-dimensional (2-D)
      CD34(+) cell culture, 3-D culture produced 30-100% higher total cells and
      progenitors without exogenous cytokines. With thrombopoietin and flt-3/flk-2
      ligand, it supported two- to three-fold higher total cell number (62.1- vs. 24.6
      fold), CD34(+) cell number (6.8- vs. 2.8-fold) and colony-forming unit (CFU)
      number for 7-9 weeks (n = 6), indicating a hematopoiesis pathway that promoted
      progenitor production. Culture in 3-D nonwoven matrices enhanced cell-cell and
      cell-matrix interactions and allowed 3-D distribution of stromal and
      hematopoietic cells. The formation of cell aggregates and higher progenitor
      content indicated that the spatial microenvironment in 3-D culture played an
      important role in promoting hematopoiesis. This 3-D culture system can be used as
      an in vitro model to study stem cell or progenitor behavior, and to achieve
      sustained progenitor expansion.

PMID- 11454312
TI  - Factors regulating the cytotoxic activity of the human natural killer cell line,
      NK-92.
AB  - NK-92, a highly cytotoxic, interleukin-2 (IL-2)-dependent human natural killer
      (NK) cell line, has been of interest for basic and translational research. We
      report on a comprehensive analysis of NK-92 for factors implicated in NK
      cytotoxicity to elucidate factors underlying NK-92's high cytolytic activity and
      target range. Thus, we hope to develop a method to identify patients best suited
      to NK-92 immunotherapy. In addition, as a model system, we hope to increase
      understanding of the basis for the elevated activity exhibited by activated NK
      (ANK) cells. NK-92 exhibits an unusual receptor expression profile, expressing a
      relatively large number of activating (NKp30, NKp46, 2B4, NKGD, E, CD28)
      receptors. Conversely, it expresses few inhibitory receptors (NKGA/B, low levels
      of KIR2DL4, ILT-2), lacking most of the killer inhibitory receptors (KIRs)
      clonally expressed on normal NK cells. In addition, NK-92 expresses high levels
      of molecules involved in the perforin-granzyme cytolytic pathway as well as
      additional cytotoxic effector molecules including tumor necrosis factor (TNF)
      superfamily members FasL, TRAIL, TWEAK, TNF-alpha, indicating the ability to kill
      via alternative mechanisms. NK-92 also expresses other molecules implicated
      immune effector cell regulation (CD80, CD86, CD40L, TRANCE) whose relevance in NK
      killing is unclear. This study provides initial data to develop a method to
      identify NK-92 susceptible cells (cells expressing ligands for NK-92 activating
      receptors ie CD48 for 2B4 and CD80/86 for CD28). Furthermore, this work suggests
      mechanisms that may contribute to ANK cell activity, including modulation of
      receptor expression to favor activation, up-regulation of cytotoxic effector
      molecules, and acquisition of new cytolytic pathways.

PMID- 11454313
TI  - Jurkat cell-reactive anti-thymocyte globulin assessed ex vivo by flow cytometry
      persists three weeks in circulation.
AB  - Rabbit anti-thymocyte globulin (ATG-Fresenius) is a polyclonal anti-serum raised
      against the lymphoblastic T cell line Jurkat. It is used for in vivo depletion of
      host and donor T cells for allogeneic stem cell transplantation. After
      administration of 90 mg/kg prior to transplant, rabbit immunoglobulin G (IgG)
      remains present for 4-5 weeks, but it is unknown how long T cell-reactive
      antibodies persist. Therefore, we measured anti-Jurkat antibodies by flow
      cytometry. The detection limit for Jurkat-reactive antibodies was 0.1 microg/ml
      rabbit IgG; half-maximal labeling of Jurkat cells required 183 microg/ml rabbit
      ATG. The mean half-life of Jurkat-reactive antibodies in 7 patients was 4 days.
      Detectable levels persisted up to 3 weeks with antibody levels equivalent to 0.2
      4.1 microg/ml rabbit ATG. Jurkat-reactive antibodies were eliminated two-fold
      faster than rabbit IgG, as assessed by enzyme-linked immunosorbent assay (ELISA).
      The results suggest that in patients pretreated with ATG before transplantation,
      residual anti T-cell antibodies may effectively modulate recovery of T cells
      generated after transplantation, thereby lowering the incidence of severe GVHD.

PMID- 11454314
TI  - Expansion of megakaryocyte precursors and stem cells from umbilical cord blood
      CD34+ cells in collagen and liquid culture media.
AB  - Umbilical cord blood (UCB) is now commonly used as a source of stem cells for
      hematopoietic reconstitution following myeloablative therapy in patients with a
      variety of diseases. Although UCB is a rich source of stem cells, platelet
      engraftment occurs at a median of 71 days which is significantly prolonged
      compared to allogeneic bone marrow. The number of megakaryocyte (MK) precursors
      in stem cell harvests appears to correlate inversely with the time to platelet
      engraftment. In an effort to increase the number of platelet precursors, we
      cultured CD34-selected cord blood mononuclear cells (MNC) in serum-free collagen
      medium with numerous cytokine combinations. The cells were cultured with four
      cytokines: interleukin-3 (IL-3), thrombopoietin (TPO), stem cell factor (SCF),
      and Flt-3); five cytokines, IL-3, TPO, SCF, Flt-3 plus granulocyte-macrophage
      colony-stimulating factor (GM-CSF), or erythropoietin (Epo); or all six cytokines
      in combination. After 16 days, significant expansion of MK precursors (CD41(+))
      and stem cells (CD34(+) and AC133(+) cells) were seen in cells cultured in IL-3,
      TPO, SCF, and Flt-3 with or without GM-CSF compared to the combinations that
      contained Epo (p < 0.05). Similar studies were performed using liquid culture
      medium, and after 14 days the number of MNCs, CD34(+), AC133(+), CD41(+), and
      CD61(+) cells were higher in the UCB cells cultured in IL-3, TPO, SCF, and Flt-3
      compared to those cultured with those four cytokines plus GM-CSF. These results
      demonstrate that UCB stem cells can be effectively expanded ex vivo and enriched
      with platelet precursors using TPO, SCF, Flt-3, and IL-3, whereas the addition of
      Epo and GM-CSF is unnecessary.

PMID- 11454315
TI  - Endogenous megakaryocytic colony formation and thrombopoietin sensitivity of
      megakaryocytic progenitor cells are useful to distinguish between essential
      thrombocythemia and reactive thrombocytosis.
AB  - Diagnosis of essential thrombocythemia (ET) is controversial and remains mainly
      an exclusion diagnosis. Endogenous megakaryocyte colony (EMC) formation have been
      largely evaluated to identify specific criteria for ET, but results are impeded
      by the lack of medium standardization. We evaluated megakaryocyte (MK) colony
      formation in a serum-free collagen-based medium, without cytokine and in the
      presence of various concentrations of thrombopoietin (TPO). Thirty-six bone
      marrows from patients diagnosed with ET (n = 11), polycythemia vera (PV; n = 12),
      reactive thrombocytosis (RT; n = 6) and healthy donors (n = 7) were assessed. We
      demonstrate that 11 out 11 of the ET patients had spontaneous megakaryocyte
      colony-forming unit (CFU-MK) formation, in contrast to none of the RT patients
      and healthy donors. MK progenitors from ET patients remained responsive to TPO,
      because exogenous addition of TPO significantly increased cloning efficiency.
      Moreover, at low doses of TPO (0.5 ng/ml and 5 ng/ml), the number of positive
      cultures and mean number of TPO stimulated CFU-MK were significantly higher in
      cultures of cells from patients with ET than in patients with RT. In summary, we
      have described a standardized serum-free, collagen-based assay that allows
      differential diagnosis of ET and RT, according to endogenous CFU-MK formation and
      sensitivity to TPO.

PMID- 11454316
TI  - Amelioration of steroid-resistant chronic graft-versus-host-mediated liver
      disease via tacrolimus treatment.
AB  - Liver disease associated with chronic graft-versus-host disease (cGVHD) is a
      major cause of mortality and morbidity. Steroids and cyclosporin (CSA), which are
      the standard therapy, give rather disappointing results, and toxicity is high.
      Tacrolimus (FK506) is a potent macrolide lactone immunosuppressant that is used
      in the prevention of solid organ rejection. This study evaluated the therapeutic
      role of FK506 in the treatment of severe cGVHD-mediated liver disease that did
      not respond to combined steroids and CSA therapy. Fifteen patients with various
      hematological disorders who underwent allogeneic stem cell transplantation were
      enrolled in the study. All patients had severe cholestatic liver disease
      disturbances and underwent liver biopsy, which was compatible with cGVHD-mediated
      liver disease. All the patients were negative for markers of chronic liver
      disease, including viral serology. They received FK506 orally (4-20 mg/day
      according to serum levels), and were evaluated biweekly by physical examination
      and liver function tests. Patients were followed for a median of 12 months (range
      3-24 months). FK506 treatment ameliorated liver functions in 9 of 15 patients
      (60%), 5 of whom demonstrated complete normalization of liver enzymes (33%). In 5
      patients, no major effect was observed, and 1 patient showed deterioration of his
      liver functions. Mean GGT levels decreased from 171.5 to 55.6 within 6 months of
      treatment. Median time to response was 3 months (range 1-11). Side effects were
      generally transient. Treatment with FK506 was found to be effective in the
      majority of patients with steroid and CSA-resistant cGVHD-associated liver
      disease, with manageable side effects. In view of these findings, FK506 may yet
      evolve into first line therapy for cGVHD induced liver toxicity.

PMID- 11454317
TI  - Real-time quantitative Y chromosome-specific PCR (QYCS-PCR) for monitoring
      hematopoietic chimerism after sex-mismatched allogeneic stem cell
      transplantation.
AB  - Y chromosome-specific sequences can be used to detect remaining male cells after
      sex-mismatched allogeneic blood stem cell transplantation (HSCT) involving a male
      patient and female donor, which represents approximately 25% of all cases. We
      developed a quantitative Y chromosome-specific PCR assay (QYCS-PCR) based on the
      DFFRY gene for the determination of hematopoietic donor chimerism. We analyzed
      blood and marrow samples from more than 40 patients at various time points after
      both standard and nonmyeloablative allogeneic HSCT. We found that real-time PCR
      combines extreme sensitivity, with a detection level of less than 1 male in
      100,000 female cells (<0.001%), with very good reproducibility, especially in the
      important range of minor host chimerism. QYCS-PCR results were in close agreement
      with data from other techniques as bcr/abl-PCR and/or fluorescent in situ
      hybridization (FISH) analysis. In two relapsed patients, increasing numbers of Y
      positive hematopoietic cells indicated recurrence of malignant disease prior to
      clinical confirmation. In conclusion, quantitative Y chromosome-specific PCR is a
      promising approach for monitoring the extent of chimerism in blood and other
      tissues after sex-mismatched hematopoietic stem cell transplantation (HSCT) or
      organ transplantation.

PMID- 11454318
TI  - Mature myeloid dendritic cells for clinical use prepared from CD14+ cells
      isolated by immunomagnetic adsorption.

PMID- 11454319
TI  - Ex vivo expansion of hematopoietic cells: what is the clinical need?

PMID- 11454320
TI  - Early involvement of the tegmentopontine reticular nucleus during the evolution
      of Alzheimer's disease-related cytoskeletal pathology.
AB  - The tegmentopontine reticular nucleus (nucleus of Bechterew) plays a crucial role
      in the generation of horizontal saccades and smooth pursuit movement of the eyes.
      The evolution of Alzheimer's disease-related cytoskeletal pathology was studied
      of this nucleus was studied in 27 autopsy cases at different stages of the
      cortical neurofibrillary pathology (NFT/NT stages I--VI). The first cytoskeletal
      changes were seen at stages I and II (preclinical Alzheimer's disease). At stages
      III and IV (incipient Alzheimer's disease), the nucleus exhibited a marked
      pathology, and it was severely involved at stages V and VI (clinically overt
      Alzheimer's disease). Damage to the tegmentopontine reticular nucleus most
      probably contributes to the hypometrie of horizontal saccades and the slowing of
      smooth pursuits that characteristically develop in patients suffering from
      Alzheimer's disease. Given the fact that pathological alterations of the
      tegmentopontine reticular nucleus begin early during the evolution of the
      underlying process, the question arises as to whether dysfunctional horizontal
      saccades and abnormal smooth pursuits could be employed as means of screening or
      diagnosing Alzheimer's patients in the very earliest stages of the disease.

PMID- 11454321
TI  - Hippocampal estrogen beta-receptor immunoreactivity is increased in Alzheimer's
      disease.
AB  - Post-menopausal estrogen use reduces the risk and severity of Alzheimer's disease
      (AD). The present study investigates the distribution of both estrogen receptors
      ER alpha and ER beta in the human hippocampus in aged controls and in AD cases
      with immunohistochemistry. No ER alpha immunoreactivity was observed both in
      controls and in AD cases. On the other hand, ER beta was observed in some
      neuronal cells in the hippocampal subfields CA1--4, in astrocytes and in
      extracellular deposits both in controls and AD cases. The ER beta
      immunoreactivity was distinctly increased in all AD cases in cellular and
      extracellular localizations indicating a role for ER beta-mediated estrogen
      effects in AD-related neuropathology. This study provides the first demonstration
      of ER beta in human hippocampus in aged controls compared to AD cases.

PMID- 11454322
TI  - Attenuation of seizures induced by homocysteic acid in immature rats by
      metabotropic glutamate group II and group III receptor agonists.
AB  - Previous studies demonstrated that selected agonists for metabotropic glutamate
      group II and group III receptors can provide protection against seizures in adult
      animals. The present study has examined the potential effect of some of these
      compounds on seizures induced in immature rats by intracerebroventricular
      infusion of DL-homocysteic acid (DL-HCA, 600 nmol/side). Rat pups were sacrificed
      during generalised clonic-tonic seizures, 50--60 min after infusion. Comparable
      time intervals were used for sacrificing the pups which had received the
      protective drugs. The anticonvulsant effect was evaluated according to the
      suppression of behavioural manifestations of seizures and the protection of
      energy metabolite changes which normally accompany these seizures (large
      decreases of glucose and glycogen, and approximately 7- to 10-fold accumulation
      of lactate). Partial protection was exhibited by group II mGluR agonist
      (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV, 0.6 nmol) and this
      effect was abolished after pretreatment with an antagonist for group II mGluRs
      (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG, 100 nmol). In high doses (5-
      100 nmol), however, DCG IV evoked seizures which were prevented by AP7,
      suggesting that the convulsant effect was mediated by interaction with NMDA
      receptors. A pronounced anticonvulsant effect against DL-HCA-induced seizures was
      achieved with low doses of a highly selective group II mGluR agonist (2R,4R)-4
      aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC, 0.6 nmol), group II agonist and
      group I mGluR antagonist (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4-C3HPG, 0.6
      nmol) and group III mGluR agonist (RS)-1-amino-3-(phosphonomethylene) cyclobutane
      carboxylic acid (32 nmol). Generalised clonic--tonic seizures were completely
      suppressed and the metabolic changes were markedly ameliorated, there being only
      a 1.5-, 2- and 2.5-fold rise of lactate, respectively. Higher doses of (S)-4
      C3HPG (1--100 nmol) were, however, less anticonvulsant than low doses. The
      present results have confirmed that mGluRs may be considered a potential target
      for treatment of epilepsy.

PMID- 11454323
TI  - Lowering of the potassium concentration induces epileptiform activity in guinea
      pig hippocampal slices.
AB  - Extra- and intracellular recording techniques were used to study the epileptiform
      activity generated by guinea-pig hippocampal slices perfused with low potassium
      containing artificial cerebrospinal fluid. Extracellular field potentials were
      recorded in CA1 and CA3 regions along with intracellular recordings in CA3
      subfield. Reduction of the extracellular potassium concentration [K(+)](o) from 4
      to 2 mM caused a transient neuronal hyperpolarisation which was followed by a
      repolarisation and subsequent depolarisation period. Paroxysmal depolarisation
      shifts occurred during the transient hyperpolarisation period while epileptic
      field potentials (EFP) appeared in the late repolarisation or early
      depolarisation phase. EFP elicited by reduction of [K(+)](o) were neither
      affected by blockade of N-methyl-D-aspartate (NMDA) glutamate-subreceptor or
      gamma aminobutyric acid receptor, nor by application of the organic calcium
      channel blocker nifedipine or the anticonvulsant drugs carbamazepine and valproic
      acid. Upon application of non-NMDA glutamate-subreceptor blocker the EFP were
      abolished in all trials, while application of the organic calcium channel blocker
      verapamil only suppressed the EFP in some cases. The results point to a novel
      mechanism of epileptogenesis and may provide an in vitro model for the
      development of new drugs against difficult-to-treat epilepsy.

PMID- 11454324
TI  - Correspondence between short-latency somatosensory evoked brain potentials and
      cortical magnetic fields following median nerve stimulation.
AB  - We investigated the somatosensory evoked cortical magnetic field (SEF) components
      corresponding to the somatosensory evoked potential (SEP) components between 20
      and 30 ms after median nerve stimulation. SEP and SEF were simultaneously
      recorded after right median nerve stimulation in seven healthy subjects. Twenty
      single-sweep epochs of SEF and SEP were selected, in which the first SEF
      component at 20 ms, 1M, and the second component at 30 ms, 2M, were identifiable.
      The selected epochs were re-averaged at the peaks of 1M and 2M as the triggering
      periods (zero ms). The width of the deflection, the temporal dispersion (TD), of
      SEP components, P20 and N30 (Fz-A2), N20, cP25 and cN30 (C3-Fz), N20 and pP30 (P3
      A2), and N20 and P30 (P3-Fz), were compared between three averaging conditions.
      The N20/P20 components showed significantly smaller TDs when the epochs were
      averaged at the 1M peak (one-way factorial ANOVA, P<0.02) than those of the
      control, but averaging at the 1M peak did not decrease the TD of N30/P30. On
      averaging at the 2M peak, the TDs of N30/P30 components recorded from Fz-A2 and
      P3-Fz were smaller than those of the control. Neither the averaging at the 1M
      peak nor that at the 2M peak decreased the TD of the cP25 and cN30 components.
      Source analysis showed that the equivalent current dipoles (ECDs) for both 1M and
      2M were located around the central sulcus, possibly in the primary somatosensory
      cortex (SI). We confirmed that the 1M and 2M temporally linked with N20/P20 and
      N30/P30, respectively. The difference of TD of N20/P20 and N30/P30 indicated that
      the neural pathways to the responses to N20/P20 and N30/P30 might be independent.

PMID- 11454325
TI  - Methylmercury has a selective effect on mitochondria in cultured astrocytes in
      the presence of [U-(13)C]glutamate.
AB  - The effect of methylmercury on glutamate metabolism was studied by (13)C magnetic
      resonance spectroscopy. Cerebral cortical astrocytes were pretreated with
      methylmercury, either 1 microM for 24 h, or 10 microM for 30 min, and
      subsequently with 0.5 mM [U-(13)C]glutamate for 2 h. Labeled glutamate,
      glutamine, aspartate and glutathione were present in cell extracts, and
      glutamine, aspartate and lactate in the medium of all groups. HPLC analysis of
      these amino acids showed no changes in concentrations between groups.
      Surprisingly, the amounts of [U-(13)C]glutamate and unlabeled glucose taken up by
      the astrocytes were unchanged. Furthermore, the amounts of most metabolites
      synthesized from [U-(13)C]glutamate were also unchanged in all groups. However,
      formation of [U-(13)C]lactate was decreased in the 10 microM methylmercury group.
      This was not observed for labeled aspartate. It is noteworthy that both [U
      (13)C]lactate and [U-(13)C]aspartate can only be derived from [U-(13)C]glutamate
      via mitochondrial metabolism. [U-(13)C]glutamate enters the tricarboxylic acid
      cycle (located in mitochondria) after conversion to 2-[U-13C]oxoglutarate and [U
      (13)C]aspartate is formed from [U-(13)C]oxaloacetate, as is [U-(13)C]lactate. [U
      (13)C]lactate can also be formed from [U-(13)C]malate. This differential effect
      on labeled aspartate and lactate indicates cellular compartmentation and thus
      selective vulnerability of mitochondria within the astrocytes to the effects of
      methylmercury. The decreased lactate production from glutamate might be
      detrimental to surrounding cells since lactate has been shown to be an important
      substrate for neurons.

PMID- 11454326
TI  - Sleep inducing effects of propofol microinjection into the medial preoptic area
      are blocked by flumazenil.
AB  - The intravenous anesthetic, propofol, has been shown to increase sleep when
      microinjected into the medial preoptic area (MPA) of the rat. Similar increases
      in sleep have also been observed with triazolam, pentobarbital and ethanol
      microinjection. Together, these findings implicate the MPA as an important
      anatomic site mediating the effects of sedatives on naturally occurring sleep.
      Although the molecular mechanism by which propofol in the MPA acts to induce
      sleep is unclear, potentiating effects on the GABA(A) receptor complex may play a
      role. To assess this possibility, we microinjected propofol alone, and in
      combination with the benzodiazepine receptor antagonist flumazenil, into the MPA.
      At a dose of 0.76 microg, flumazenil had no effect on sleep when given alone, and
      completely blocked the increase in sleep caused by a 40-ng dose of propofol
      although it did not affect the increase in sleep caused by an 80-ng dose of
      propofol. These data suggest that the sleep inducing property of propofol is in
      part mediated by direct or indirect actions on the GABA(A)-benzodiazepine
      receptor complex.

PMID- 11454327
TI  - Temporal and spatial distribution of Fos protein in the parabrachial nucleus
      neurons during experimental tooth movement of the rat molar.
AB  - The present study was undertaken to reveal spatio-temporal changes in the
      distribution of Fos-like immunoreactive (-IR) neurons in the parabrachial nucleus
      (PBN), one of the important relay nuclei for processing autonomic and
      somatosensory information from the oro-facial regions, following the induction of
      experimental tooth movement in rat upper molars. The experimental tooth movement
      was induced by the insertion of elastic rubber between the first and second upper
      molars. In normal animals, the PBN contained a smaller number of Fos-IR neurons.
      Following experimental tooth movement, the Fos-IR neurons increased in number
      significantly on both the ipsilateral and contralateral PBN, reaching a maximum
      at 4 h (about 10 times that of normal animals), and then decreased gradually.
      However, a significant number of Fos-IR neurons remained at 24 h post-operation.
      Remarkable side-by-side differences in the number of Fos-IR neurons were
      recognized at 1 to 4 h following the experimental tooth movement. Their number
      returned to normal (basal) levels at 5 days post. All subnuclei of PBN showed
      similar temporal changes in the number of Fos-IR neurons, this being particularly
      apparent in lateral PBN. Administrations of morphine (3 and 10 mg/kg, i.p.)
      drastically reduced the induction of Fos-IR neurons in all subnuclei of both the
      ipsilateral and contralateral PBN in a dose-dependent manner, and its effect was
      antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The reduction of Fos
      IR neurons by morphine pretreatment suggests that the appearance of Fos-IR
      neurons in the PBN may be partly due to the noxious stimulation and/or stress
      arising from tooth movement. The bilateral expression of Fos-IR neurons in the
      PBN indicates that the experimental tooth movement causes the activation of PBN
      neurons for the processing of somatosensory as well as autonomic information. The
      prolonged expression of Fos-IR neurons in all the subnuclei of bilateral PBN
      reflects clinical features of the transient discomfort and/or abnormal
      sensations, which many patients often complain about during orthodontic
      treatment.

PMID- 11454328
TI  - The effect of ethanol on metabolic, hemodynamic and electrical responses to
      cortical spreading depression.
AB  - Alcohol induces a decrease in cerebral blood flow (CBF) and metabolic rate,
      mitochondrial damage and other impairments in brain function and structure.
      Cortical spreading depression (CSD) is a phenomenon causing changes in ion
      homeostasis and raises energy demand, mitochondrial activity and CBF. It is of
      great interest to study the effect of ethanol on brain response under a challenge
      of increasing oxygen demand by inducing CSD. A special multisite assembly (MSA)
      was constructed to evaluate metabolic (mitochondrial NADH), hemodynamic
      (reflectance) and electrical (DC potential) activities from four parasagittally
      adjacently arranged areas of the cerebral cortex, continuously and simultaneously
      in vivo. Three CSD cycles were initiated every 30 min before and after ethanol or
      saline infusion over 4.5 h. During CSD amplitude changes of reflectance, NADH and
      DC potential as well as propagation rates and wave frequency were calculated.
      After ethanol infusion CSD showed a decrease in the negative shift of the DC
      potential, and alterations in the biphasic responses in reflectance, which may
      indicate alteration in blood volume: unclear responses in the initial
      vasoconstriction phase and a significant increase in the subsequent
      vasodilatation phase. The reduction in the amplitude of the NADH oxidation cycle
      may depict a decrease in energy production, which could also be indicated by a
      decline in wave frequency (prolonging the recovery phase of the CSD). The
      decrease in propagation rate indicates a decline in tissue excitability and in
      the CSD initiation mechanism induced by ethanol treatment.

PMID- 11454329
TI  - Stress-induced sensitization of CRH-ir but not P-CREB-ir responsivity in the rat
      central nervous system.
AB  - There is some evidence that a traumatic life event can induce long-term
      alterations in corticotropin-releasing hormone (CRH) producing neurons in humans,
      which may play a role in the pathophysiology of anxiety disorders, including post
      traumatic stress disorder (PTSD). To study the long-term effects of a traumatic
      event on brain CRH-immunoreactivity (CRH-ir) and phospho-cAMP response element
      binding protein-immunoreactivity (P-CREB-ir), rats were exposed to a single
      session of foot shocks (preshocked) or no shocks (control). Two weeks later half
      of the control rats and half of the preshocked rats received an electrified prod
      in the home cage for 15 min and behavior was recorded. Fifteen minutes after the
      removal of the prod rats were perfused and brain sections were stained for CRH-ir
      and P-CREB-ir. There was no basal difference between preshocked and control rats
      in brain CRH-ir and P-CREB-ir. Exposure to the electrified prod induced a
      significant increase in CRH-ir in the paraventricular nucleus of the
      hypothalamus, the median eminence and the central amygdala in preshocked rats,
      but not in control rats. The electrified prod increased the number of P-CREB-ir
      neurons in the paraventricular nucleus of the hypothalamus and the locus
      coeruleus, but the preshock experience did not affect this response. In an
      additional experiment with a similar design plasma hormone levels were measured
      14 days after the foot shocks. The preshock experience sensitized the shock prod
      induced ACTH and corticosterone response. No behavioral differences between
      preshocked and control rats were found during the shock prod tests. We suggest
      that long-term stress-induced changes in neuropeptide dynamics of CRH-ir neurons
      may play a role in long-term stress-induced neuroendocrine sensitization.

PMID- 11454330
TI  - Delayed stress-induced increase in tissue level of cholecystokinin in rat
      prefrontal cortex: modulation by microdialysis probe implantation and systemic
      ketamine.
AB  - In the brain, the neuropeptide cholecystokinin (CCK) appears to be involved in
      the mediation of stress responses. Here we provide new evidence that mild stress
      induces long-term changes in CCK-like immunoreactivity (CCK-LI) in the prefrontal
      cortex (PFC). The changes in CCK-LI show a biphasic pattern, with a decrease 20
      min after and an increase 8 h after mild stress. These changes seem to be region
      specific. Measurement of CCK mRNA in prefrontal cortex neurons 4 or 8 h after the
      stress stimulus did not reveal changes in mRNA levels, suggesting that afferent
      CCK-containing neuron terminals may be more affected than local cortical CCK
      ergic neurons. Furthermore, treatment with the glutamate NMDA receptor antagonist
      ketamine, led to more pronounced decreases in CCK-LI observed within 20 min after
      mild stress and counteracted the stress induced increase in cortical CCK-LI
      levels observed at 8 h. Implantation of a microdialysis probe in the PFC affected
      the response to mild stress, with no significant decrease in the CCK-LI level 20
      min after, and attenuated reactivity to stress 8 h after the saline injection.
      Our results indicate that a mild stressful stimulus such as an intraperitoneal
      saline injection may have long-lasting effects on CCK-ergic transmission in the
      PFC. The use of microdialysis to study stress induced in vivo CCK-LI release in
      awake animals may, however, be significantly compromised by the impact of the
      microdialysis probe implantation on CCK-ergic mechanisms in the PFC. In addition,
      we hypothesize that subanesthetic doses of the psychotomimetic drug ketamine
      interfere with CCK-ergic mechanisms in the PFC during stress.

PMID- 11454331
TI  - Brain plasticity: 'visual' acuity of blind persons via the tongue.
AB  - The 'visual' acuity of blind persons perceiving information through a newly
      developed human-machine interface, with an array of electrical stimulators on the
      tongue, has been quantified using a standard Ophthalmological test (Snellen
      Tumbling E). Acuity without training averaged 20/860. This doubled with 9 h of
      training. The interface may lead to practical devices for persons with sensory
      loss such as blindness, and offers a means of exploring late brain plasticity.

PMID- 11454332
TI  - Negative chronotropism of the heart is inhibited with lesions of the caudal
      medulla in the rat.
AB  - Neurons in the ventrolateral medulla are essential for cardiorespiratory
      regulation. It has been suggested that neurons in the caudal ventrolateral
      medulla are responsible for the negative chronotropic effect of the heart, at
      least in carnivores, because injection of glutamate into this area decreases
      heart rate significantly. In the present study, we monitored heart rate both
      before and after injections of the excitotoxin ibotenic acid into the most caudal
      part of the ventrolateral medulla in rats. We found that resting heart rate
      increased significantly by more than 53% (P<0.0001) after the ibotenic acid
      injections. This result suggests that neurons located in the caudal ventrolateral
      medulla are responsible for the negative chronotropic effect of the heart in the
      rat, especially its most caudal part.

PMID- 11454333
TI  - Depolymerization of the capsular polysaccharide from Vibrio cholerae O139 by a
      lyase associated with the bacteriophage JA1.
AB  - We have studied the interaction between the Vibrio cholerae O139 specific phage
      JA1, belonging to the Podoviridae family, and the capsular polysaccharide (CPS)
      of the parent strain from which the phage was isolated. Upon incubation of the
      JA1 phage with the CPS, oligosaccharides were isolated and purified. The
      oligosaccharides derived from one (shown below) and two repeating units of the
      CPS were characterized using NMR spectroscopy, mass spectrometry and sugar
      analysis (structure: see text). The cleavage was found to occur by beta
      elimination at the 4-substituted alpha-linked galacturonic acid, which results in
      a 4-deoxy-beta-L-threo-hex-4-enopyranosyl uronic acid group (Sug). The enzyme
      associated with the JA1 phage responsible for the depolymerization of the V.
      cholerae O139 CPS is thus a lyase.

PMID- 11454334
TI  - Structural analysis of Gigartina pistillata carrageenans (Gigartinaceae,
      Rhodophyta).
AB  - The chemical structure of carrageenans produced by the gametophytic and
      tetrasporophytic life cycle phases of Gigartina pistillata has been determined by
      permethylation analysis, IR and 13C NMR spectroscopies. The chemistry of the
      galactans varies according to the biological phases of the plant, the
      gametophytic alga produces heterogeneous kappa-iota type carrageenan containing
      minor amounts of nu-carrabiose. The tetrasporophytic alga synthesizes a complex
      sulfated galactan composed of lambda-, xi-, pi-carrabioses and sulfated
      carrabioses containing 3-linked galactopyranose 2,6-disulfate.

PMID- 11454335
TI  - Structural studies on fucoidans from the brown seaweed Sargassum stenophyllum.
AB  - The brown seaweed Sargassum stenophyllum biosynthesizes two different sets of
      fucoidans. One of them is characterized by higher percentages of glucuronic acid
      and fewer sulfate groups, which are situated on different sugar units. alpha-L
      Fucose was the major component but other sugars like beta-D-galactose, beta-D
      mannose, alpha-D-glucuronic acid, alpha-D-glucose and beta-D-xylose were also in
      substantial amounts. Fucoidans from the other set contain small amounts of alpha
      D-glucuronic acid and high percentages of sulfate groups, which are concentrated
      on the fucose residues, with only fucose and galactose as major components.
      Structural studies of one fucoidan from each set suggest that these products have
      a general basic structure that has a formal resemblance to that of the
      fucosylated chondroitin sulfates from the body wall of sea cucumbers, namely, a
      linear core (formed mainly by (1-->6)-beta-D-galactose and/or (1-->2)-beta-D
      mannose units) with branched chains of 'fucans' (formed by (1-->3) and/or (1-->4)
      alpha-L-fucose, (1-->4)-alpha-D-glucuronic acid, terminal beta-D-xylose and,
      sometimes, (1-->4)-alpha-D-glucose). In fucoidans from the second set, the 'core'
      is reduced to short galactan chains.

PMID- 11454336
TI  - Extracellular polysaccharides of modified strains of Erwinia spp.
AB  - The structure of the extracellular polysaccharide (EPS) produced by Erwinia
      chrysanthemi strain A2148 has been determined using low pressure size-exclusion
      and anion-exchange chromatographies, high pH anion-exchange chromatography,
      glycosyl-linkage analysis, and 1D 1H NMR spectroscopy. The polysaccharide is
      structurally similar, if not identical, to the EPS produced by E. chrysanthemi
      strain A350. A streptomycin-resistant strain of E. chrysanthemi Ech6 (Ech6S(+))
      has been generated and has an elevated production of EPS, as does a streptomycin
      resistant strain (Ech9Sm6) of E. chrysanthemi Ech9. These modified E.
      chrysanthemi spp. have been ribotyped and found to be closely related to their
      parent strains.

PMID- 11454337
TI  - Substrate-dependent chemoselective aldose-aldose and aldose-ketose isomerizations
      of carbohydrates promoted by a combination of calcium ion and monoamines.
AB  - Epimerization of aldoses at C-2 has been extensively investigated by using
      various metal ions in conjunction with diamines, monoamines, and aminoalcohols.
      Aldoses are epimerized at C-2 by a combination of alkaline-earth or rare-earth
      metal ions (Ca(2+), Sr(2+), Pr(3+), or Ce(3+)) and such monoamines as
      triethylamine. In particular, the Ca(2+)-triethylamine system proved effective in
      promoting aldose-ketose isomerization as well as C-2 epimerization of aldoses.
      13C NMR studies using D-(1-(13)C)glucose and D-(1-(13)C)galactose with the
      CaCl(2) system in CD(3)OD revealed that the C-2 epimerization proceeds via
      stereospecific rearrangement of the carbon skeleton, or 1,2-carbon shift, and
      ketose formation proceeds partially through an intramolecular hydrogen migration
      or 1,2-hydride shift and, in part, via an enediol intermediate. These
      simultaneous aldose-aldose and aldose-ketose isomerizations showed interesting
      substrate-dependent chemoselectivity. Whereas the mannose-type aldoses having 2,3
      erythro configuration (D-mannose, D-lyxose, and D-ribose) showed considerable
      resistance to both the C-2 epimerization and the aldose-ketose isomerization, the
      glucose-type sugars having 2,3-threo and 3,4-threo configurations, D-glucose and
      D-xylose, are mainly epimerized at C-2 and those having the 2,3-threo and 3,4
      erythro configurations, D-galactose and D-arabinose, were mostly isomerized into
      2-ketoses. These features are of potential interest in relevance to biomimic
      sugar transformations by metal ions.

PMID- 11454338
TI  - Synthesis and anticancer activity of novel chiral D-glucose derived bis
      imidazoles and their analogs.
AB  - A series of novel D-glucose derived bis-imidazoles and their analogs, which
      possess potential in bioorganic and supramolecular chemistry, were designed and
      synthesized from methyl alpha-D-glucoside through protection, bis-bromination, N
      alkylation and deprotection. All new compounds were characterized by HRMS, 1H,
      13C and DEPT NMR spectroscopy as well as elemental analysis. The 1H-(1)H and 1H
      (13)C 2D NMR spectra for some compounds were also recorded. Some regular features
      of 13C and 1H NMR spectra were summarized. The anticancer activity of some
      compounds was evaluated.

PMID- 11454339
TI  - D-Fructose-L-sorbose interconversions. Access to 5-thio-D-fructose and
      interaction with the D-fructose transporter, GLUT5.
AB  - Epimerisation and subsequent functionalization at C-5 of D-fructopyranose
      derivatives under Mitsunobu and Garegg's conditions provided efficient access to
      5-thio-D-fructose (2) as well as to 5-azido-5-deoxy-1,2-O-isopropylidene-beta-D
      fructopyranose (19), a known precursor to 2,5-deoxy-2,5-imino-D-mannitol (3). The
      interaction of 2 with the D-fructose transporter GLUT5, was found to be weaker
      than that of D-fructose, a result that suggests involvement of the ring oxygen
      atom in the recognition of D-fructose by GLUT5.

PMID- 11454340
TI  - Structure of the O-specific polysaccharide of Citrobacter braakii O7a,3b,1c.
AB  - The following structure of the O-specific polysaccharide of Citrobacter braakii
      O7a,3b,1c was established using sugar and methylation analyses and NMR
      spectroscopy, including 2D COSY, TOCSY, NOESY, and 1H, 13C heteronuclear single
      quantum coherence (HSQC) experiments: (struture: see text). The main D-mannan
      chain of the polysaccharide studied has the same structure as the O-specific
      polysaccharide of Escherichia coli O9, Klebsiella pneumoniae O3, and Hafnia alvei
      PCM 1223.

PMID- 11454341
TI  - A very efficient method to cleave Lipid A and saccharide components in bacterial
      lipopolysaccharides.
AB  - A novel mild procedure for the selective cleavage of ketosidic linkages is
      developed using ceric ammonium nitrate (CAN) in anhydrous N,N-dimethylformamide.
      Its application to lipopolysaccharides (LPS) is very significant because in the
      so far investigated LPS, the connection between the Lipid A region and the
      oligo(poly)saccharide part is always a keto-sugar. This procedure has been tested
      on LPS of Escherichia coli which contains Kdo as a linker between Lipid A and OPS
      and on Acinetobacter haemoliticus which contains D-glycero-D-talo-2
      octulopyranosonic acid (Ko) as a linker and it performed efficiently in both
      cases.

PMID- 11454342
TI  - Sesquiterpene lactones from Smyrnium olusatrum.
AB  - Fruits of Smyrnium olusatrum afforded three sesquiterpene lactones, namely,
      1beta,8beta-dihydroxyeudesman-3,7(11)-dien-8alpha,12-olide, 1beta,8beta
      dihydroxyeudesman-4(15),7(11)-dien-8alpha,l2-olide, and
      1beta,10alpha,4alpha,5beta-diepoxy-6beta-hydroxyglechoman-8alpha,12-olide. Four
      related known sesquiterpenes were also isolated and characterized. The structure
      elucidation of the isolated compounds was based primarily on 1D and 2D NMR
      analyses. The in vitro cytotoxicity of the extract and isolated compounds against
      P-388 mouse lymphoma cells will be also discussed.

PMID- 11454343
TI  - Monoterpene coumarins from Ferula ferulago.
AB  - Two monoterpene coumarins, designated ferulagol A and B, as well as three known
      monoterpene coumarins and three sesquiterpene lactones were isolated from the
      chloroform extract of the roots of Ferula ferulago. The structures of ferulagol A
      and B were determined to be 7-[(E)-3'-hydroxy-3',7'-dimethyl-4',6'
      octadienyloxy]coumarin and 7-[(3'Z,5'E)-7'-hydroxy-3',7'-dimethyl-3',5'
      octadienyloxy]coumarin, respectively.

PMID- 11454344
TI  - Quassinoids from Eurycoma harmandiana.
AB  - Three quassinoids, iandonosides A and B and iandonone, were isolated from the
      root of Eurycoma harmandiana, along with five known quassinoids, casteloside B,
      13 beta, 21-dihydroeurycomanone, chaparrinone, glaucarubolone and ailanquassin B
      as well as the coumarin, scopoletin. The structural elucidations were based on
      analyses of spectroscopic data.

PMID- 11454345
TI  - Three clerodane diterpenoids from Croton eluteria Bennett.
AB  - Three furanoid clerodanes have been isolated from the stem bark of Croton
      eluteria Bennett. Their structures have been established by spectroscopic
      methods. The compounds were named cascarillin B (7alpha-acetoxy-3,4,15,16-diepoxy
      12-oxo-cleroda-13(16),14-dien-20-al), cascarillin C (7alpha-acetoxy-15,16,12,20
      diepoxy-20-hydroxy-cleroda-3,4,13(16),14-triene) and cascarillin D (7alpha
      acetoxy-3,4,15,16-diepoxy-cleroda-13(16),14-dien-20-al).

PMID- 11454346
TI  - Penicillosides A-C, C-15 oxypregnane glycosides from Caralluma penicillata.
AB  - The chloroform fraction of the defatted ethanol extract from the aerial parts of
      Caralluma penicillata yielded three C-15 oxypregnane glycosides, penicillosides A
      C. Their structures were established by a combination of spectroscopic methods.

PMID- 11454347
TI  - A steroidal saponin from the seeds of Allium tuberosum.
AB  - A steroidal saponin, named tuberoside, together with seven known compounds, were
      isolated from the seeds of Allium tuberosum Rottl. ex Spreng. Its structure was
      established by spectroscopic data, hydrolysis, and comparison with spectral data
      of known compounds to be (2alpha, 3beta, 5alpha, 25S)-2,3,27-trihydroxyspirostane
      3-O-alpha-L-rhamnopyranoyl-(1-->2)-O-[alpha-L-rhamnopyranoyl-(1-->4)]-beta-D
      glucopyranoside.

PMID- 11454348
TI  - Acylated apigenin glycosides from alfalfa (Medicago sativa L.) var. Artal.
AB  - Three flavones, including 4'-O-[2'-O-E-feruloyl-O-beta-D-glucuronopyranosyl(1-
      >2)-O-beta-D-glucuronopyranoside]apigenin, 7-O-beta-D-glucuronopyranosyl-4'-O-[2'
      O-E-feruloyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D
      glucuronopyranoside]apigenin and 7-O-beta-D-glucuronopyranosyl-4'-O-[2'-O-p-E
      coumaroyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D
      glucuronopyranoside]apigenin have been identified in alfalfa var. Artal. The
      known flavone 7-O-[2-O-E-feruloyl-[beta-D-glucuronopyranosyl(1-->3)]-O-beta-D
      glucuronopyranosyl(1-->2)-O-beta-D-glucurono-pyranoside] apigenin was also
      isolated. The structures of these compounds were deduced on the basis of their
      spectral data.

PMID- 11454349
TI  - Benzopyrans from Hypericum polyanthemum.
AB  - From the aerial parts of Hypericum polyanthemum Klotzsch ex Reichardt
      (Guttiferae), three chromenes, 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl
      benzopyran; 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran and 5
      hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran were isolated. Their
      structures were determined by NMR spectroscopic analyses.

PMID- 11454350
TI  - Diels-Alder type adducts from Morus cathayana.
AB  - Two natural Diels-Alder type adducts, cathayanon A (1) and cathayanon B (2),
      resembling sanggenon C (4) and O (3), were isolated from the root bark of Morus
      cathayana. Their structures were elucidated on the basis of spectroscopic
      evidence. The structure of 1 was confirmed by the results of X-ray
      crystallographic analysis. The absolute configurations of 1 and 2 were determined
      as 2S, 3R,14S, 19S, 20R and 2S, 3R, 14R, 19S, 20R, respectively. The absolute
      configurations at C-2 and C-3 of two other known isomeric Diels-Alder adducts
      sanggenon O (3) and C (4) were deduced as 2R, 3S. Pharmacological tests indicated
      that 1 and 2 exhibited potent activities on the inhibition of HL-60 cell adhesion
      to BAEC at concentrations of 10(-5) mol l(-1), with inhibitory rates of 44.72 and
      39.02%, respectively.

PMID- 11454351
TI  - Benzophenone O-glucoside, a biogenic precursor of 1,3,7-trioxygenated xanthones
      in Hypericum annulatum.
AB  - Two benzophenones, hypericophenonoside (1) and annulatophenone (2) were isolated
      from the methanol extract of the herb of Hypericum annulatum. The structures of
      the benzophenones were established as 2'-O-beta-D-glucopyranosyl-2,4,5',6
      tetrahydroxy benzophenone (1) and 2,3',5',6-tetrahydroxy-4-methoxybenzophenone
      (2) based on spectral and chemical evidence. Hypericophenonside is the second
      benzophenone O-glycoside found in nature. Acid and enzymatic hydrolysis of (1)
      led directly to the formation of 1,3,7-trihydroxyxanthone (gentisein). This fact
      confirmed the hypothesis that some xanthones could be formed in plants by
      dehydration of 2,2'-dihydroxybenzophenones, and the intermediate precursors
      appear to be benzophenone O-glycosides ortho to the carbonyl function.

PMID- 11454352
TI  - Lignan and phenylpropanoid glycosides from Fernandoa adenophylla.
AB  - From the leaves and branches of Fernandoa adenophylla, a lignan glycoside
      (fernandoside) and a phenylpropanoid glycoside (2"-O-beta-apiosylverbascoside)
      were isolated together with 12 known compounds. The structural elucidations were
      based on analyses of physical and spectroscopic data.

PMID- 11454353
TI  - Flavonoid ketohexosefuranosides from the leaves of Crataegus pinnatifida Bge.
      var. major N.E.Br.
AB  - Four flavonoid ketohexosefuranosides, pinnatifinoside A, pinnatifinoside B,
      pinnatifinoside C, and pinnatifinoside D were isolated from the leaves of
      Crataegus pinnatifida Bge. var. major N.E.Br. Their structures were elucidated by
      spectroscopic analysis (UV, IR, MS and 1D, 2D NMR) and chemical evidence.

PMID- 11454354
TI  - Chemical constituents from Dendrobium densiflorum.
AB  - 5-[2'-(3"-Hydroxy-5"-methoxyphenyl)-ethyl]-1,3-benzodioxole and 7-hydroxy-2
      methoxy-1,4-phenanthrenedione, along with 16 known compounds were identified from
      the stems of Dendrobium densifiorum Lindl. ex Wall. (Orchidaceae). The structure
      of a previously reported compound dendroflorin obtained from the plant was
      revised on the basis of spectroscopic analysis. Among the identified compounds,
      five were found to exhibit anti-platelet aggregation activity in vitro.

PMID- 11454355
TI  - Acylated flavonoid glycosides from Bassia muricata.
AB  - From the arial parts of Bassia muricata, two acylated flavonoid glycosides
      quercetin-3-O-(6"-caffeoyl)-sophoroside and quercetin-3-O-(6"-feruloyl)
      sophoroside have been isolated together with two known flavonoid glycosides
      quercetin-3-O-sophoroside and quercetin-3,7-O-beta-diglucopyranoside, as well as
      four known triterpenoidal saponins, oleanolic acid-3-O-beta-glucopyranoside,
      chikusetsusaponin IVa, chikusetsusaponin IVa methyl ester and oleanolic acid-3,28
      beta-diglucopyranoside. The structures of the isolated compounds were verified by
      means of MS and NMR spectral analyses.

PMID- 11454356
TI  - Isoflavonoid glycosides from Dalbergia sissoo.
AB  - Two isoflavone glycosides, biochanin A 7-O-[beta-D-apiofuranosyl-(1-->5)-beta-D
      apiofuranosyl-(1-->6)-beta-D-glucopyranoside] and tectorigenin 7-O-[beta-D
      apiofuranosyl-(1-->6)-beta-D-glucopyranoside], were isolated from Dalbergia
      sissoo. Their structures were elucidated on the basis of spectral and chemical
      evidence.

PMID- 11454357
TI  - Pyrrolizidine alkaloids from Ageratum houstonianum Mill.
AB  - Four pyrrolizidine alkaloids (PA) were isolated from Ageratum houstonianum and
      their structures elucidated by spectroscopical methods. Besides the already known
      lycopsamine three new PA were found. Their structures are the 2S-2-hydroxy-2,3
      dimethyl-butanoyl-O(9) as well as the O(7) esters of retronecine and the O(9)
      derivative of heliotridine.

PMID- 11454358
TI  - Indole alkaloids from the seeds of Centaurea cyanus (Asteraceae).
AB  - Preparative RP-HPLC analysis of a methanol extract of the seeds of Centaurea
      cyanus afforded four indole alkaloids: moschamine, cis-moschamine, centcyamine
      and cis-centcyamine, the latter two being new natural products. Structures of
      these compounds were elucidated by comprehensive spectroscopic analyses. General
      toxicity of the isolates was determined by Brine Shrimp Lethality bioassay.

PMID- 11454359
TI  - Haplophytin-A and B: the alkaloidal constituents of Haplophyllum acutifolium.
AB  - During the phytochemical investigation of Haplophyllum acutifolium, two alkaloids
      named haplophytin-A (1) and B (2) have been obtained. In addition, some known
      constituents: flindersine (3), kusunokinin (4), beta-sitosterol, oleanolic acid,
      cholesterol and hexadecanoic acid, have also been obtained. The known
      constituents have never been obtained from this source. The structures of all the
      isolated constituents were elucidated by spectroscopic means. However, the
      structures of constituents 1 and 2 were further confirmed through HMBC technique.

PMID- 11454360
TI  - Minor cytotoxic and antibacterial compounds from the rhizomes of Amomum
      aculeatum.
AB  - A new cytotoxic 1,7-dioxa-dispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivative,
      aculeatin D, and a new alkenone, 5-hydroxy-hexacos-1-en-3-one, have been isolated
      as minor compounds from the rhizomes of Amomum aculeatum. Their structures have
      been determined mainly by NMR spectroscopy and mass spectrometry. Aculeatin D
      showed high cytotoxicity against the KB and the L-6 cell line with IC(50) of 0.38
      microg/ml and 1 microg/ml, respectively. Additionally, it revealed remarkable
      activity against two Plasmodium falciparum strains, as well as against
      Trypanosoma brucei rhodesiense and Trypanosoma cruzi. 5-Hydroxy-hexacos-1-en-3
      one exhibited neither cytotoxic nor antiprotozoal activity, whereas antibacterial
      testing against Bacillus cereus, Escherichia coli and Staphylococcus epidermidis
      showed moderate to strong activity for both compounds.

PMID- 11454361
TI  - An ellagic compound and iridoids from Cornus capitata root cultures.
AB  - An ellagic acid derivative, 3,3'-di-O-methylellagic acid 4-(5"-acetyl)-alpha-L
      arabinofuranoside, and two iridoid glucosides, 6alpha-dihydrocornic acid and
      6beta-dihydrocornic acid, were isolated from Cornus capitata adventitious roots
      cultured in Murashige-Skoog (Murashige, T., Skoog, F., 1962. A revised medium for
      rapid growth and bioassays with tobacco tissue cultures. Physiol. Plant. 15, 473
      487) liquid medium containing 10 microM CuSO(4). Three known related metabolites,
      i.e. stenophyllin H1, dihydrocornin and cornin were also produced in the root
      cultures. The chemical structures were characterized by analysis of spectroscopic
      data.

PMID- 11454362
TI  - A global health fund: heeding Koch's caution.

PMID- 11454363
TI  - Reducing likelihood of instrumental delivery with epidural anaesthesia.

PMID- 11454364
TI  - Persistence of group A streptococci in eukaryotic cells--a safe place?

PMID- 11454365
TI  - Amyloid proteins in pathogenesis of AA amyloidosis.

PMID- 11454366
TI  - Wanderings of the bone-marrow stem cell.

PMID- 11454367
TI  - Intrauterine devices and infertility: sifting through the evidence.

PMID- 11454368
TI  - Chromosomal aberrations, subtelomeric defects, and mental retardation.

PMID- 11454370
TI  - Extended-duration prophylaxis against venous thromboembolism after total hip or
      knee replacement: a meta-analysis of the randomised trials.
AB  - BACKGROUND: The optimum duration of prophylaxis against venous thromboembolism
      after total hip or knee replacement is uncertain. Our primary objective was to
      establish the efficacy of extended-duration prophylaxis on symptomatic venous
      thromboembolic events. METHODS: We identified randomised trials comparing
      extended-duration prophylaxis using heparin or warfarin with placebo or untreated
      control in patients undergoing elective total hip or knee replacement by
      searching electronic databases (MEDLINE, EMBASE), references from retrieved
      articles, and abstracts from conference proceedings, and by contact with
      pharmaceutical companies and investigators. Two reviewers independently extracted
      data on study design, symptomatic and symptomless venographic venous
      thromboembolism, death, and bleeding outcomes. Results from individual trials
      were combined with the Mantel-Haenszel method. FINDINGS: Nine studies met our
      inclusion criteria (3999 patients), eight with low molecular weight heparin, and
      one with unfractionated heparin. Extended-duration prophylaxis for 30-42 days
      significantly reduced the frequency of symptomatic venous thromboembolism (1.3%
      vs 3.3%, OR 0.38; 95% CI 0.24-0.61, numbers needed to treat [NNT]=50), with no
      statistical evidence of heterogeneity (x(2) test, p=0.69). There was a greater
      risk reduction in patients undergoing hip replacement (1.4% vs 4.3%, 0.33; 0.19
      0.56, 34) compared with knee replacement (1.0% vs 1.4%, 0.74; 0.26-2.15, 250). A
      significant reduction in symptomless venographic deep vein thrombosis was also
      observed (9.6% vs 19.6%, 0.48; 0.36-0.63, 10). There was no increase in major
      bleeding but extended-duration prophylaxis was associated with excess minor
      bleeding (3.7% vs 2.5%, 1.56; 1.08-2.26, numbers needed to harm [NNH]=83).
      INTERPRETATION: Among patients undergoing total hip or knee replacement, extended
      duration prophylaxis significantly reduces the frequency of symptomatic venous
      thromboembolism. The reduction in risk is equivalent to about 20 symptomatic
      events per 1000 patients treated.

PMID- 11454371
TI  - Tick-borne encephalitis in Sweden and climate change.
AB  - BACKGROUND: The incidence of tick-borne encephalitis (TBE) in Sweden has
      substantially increased since the mid-1980s. During the same period the climate
      has become milder and ticks have become more abundant. We investigated whether
      there is a link between the change in climate and the increase in incidence of
      TBE. METHODS: Since the late 1950s all cases of encephalitis admitted in
      Stockholm County have been serologically tested for TBE. We analysed the period
      1960-98 with multiple regressions. The number of days per season with
      temperatures of known importance for tick prevalence and pathogen transmission
      were studied. 2 years of temperature data were related to each TBE incidence rate
      to account for the tick's long life-span. FINDINGS: Increases in disease
      incidence was significantly related (R(2)=0.58; p<0.0001) to a combination of two
      consecutive mild winters, temperatures favouring spring development (8-10 degrees
      C) and extended autumn activity (5-8 degrees C) in the year prior to the
      incidence year, and temperatures allowing tick activity (5-8 degrees C) early in
      the incidence year. INTERPRETATIONS: The findings indicate that the increase in
      TBE incidence since the mid-1980s is related to the period's change towards
      milder winters and early arrival of spring. Other factors may have influenced TBE
      incidence such as more people in endemic locations, and increases in host animal
      populations; factors which are partly climate related. Access to TBE vaccination
      since 1986 and increased awareness of ticks might have caused an underestimation
      of the links found. Our findings also suggest that the incidence of other tick
      borne zoonoses might have been affected by the milder climate.

PMID- 11454372
TI  - Effect of low-dose mobile versus traditional epidural techniques on mode of
      delivery: a randomised controlled trial.
AB  - BACKGROUND: Epidural analgesia is the most effective labour pain relief but is
      associated with increased rates of instrumental vaginal delivery and other
      effects, which might be related to the poor motor function associated with
      traditional epidural. New techniques that preserve motor function could reduce
      obstetric intervention. We did a randomised controlled trial to compare low-dose
      combined spinal epidural and low-dose infusion (mobile) techniques with
      traditional epidural technique. METHODS: Between Feb 1, 1999, and April 30, 2000,
      we randomly assigned 1054 nulliparous women requesting epidural pain relief to
      traditional (n=353), low-dose combined spinal epidural (n=351), or low-dose
      infusion epidural (n=350). Primary outcome was mode of delivery, and secondary
      outcomes were progress of labour, efficacy of procedure, and effect on neonates.
      We obtained data during labour and interviewed women postnatally. FINDINGS: The
      normal vaginal delivery rate was 35.1% in the traditional epidural group, 42.7%
      in the low-dose combined spinal group (odds ratio 1.38 [95% CI 1.01-1.89];
      p=0.04); and 42.9% in the low-dose infusion group (1.39 [1.01-1.90]; p=0.04).
      These differences were accounted for by a reduction in instrumental vaginal
      delivery. Overall, 5 min APGAR scores of 7 or less were more frequent with low
      dose technique. High-level resuscitation was more frequent in the low-dose
      infusion group. INTERPRETATION: The use of low-dose epidural techniques for
      labour analgesia has benefits for delivery outcome. Continued routine use of
      traditional epidurals might not be justified.

PMID- 11454373
TI  - Amyloid load and clinical outcome in AA amyloidosis in relation to circulating
      concentration of serum amyloid A protein.
AB  - BACKGROUND: Reactive systemic (AA, secondary) amyloidosis occurs in chronic
      inflammatory diseases, and most patients present with nephropathy. The amyloid
      fibrils are derived from the circulating acute-phase reactant serum amyloid A
      protein (SAA), but the relation between production of fibril precursor protein,
      amyloid load, and clinical outcome in AA and other types of amyloidosis is
      unclear. METHODS: We studied amyloidotic organ function and survival
      prospectively for 12-117 months in 80 patients with systemic AA amyloidosis in
      whom serum SAA concentration was measured monthly and visceral amyloid deposits
      were assessed annually by serum amyloid P component scintigraphy. Underlying
      inflammatory diseases were treated as vigorously as possible. FINDINGS: Amyloid
      deposits regressed in 25 of 42 patients whose median SAA values were within the
      reference range (<10 mg/L) throughout follow-up, and amyloidotic organ function
      stabilised or improved in 39 of these cases. Outcome varied substantially among
      patients whose median SAA concentration exceeded 10 mg/L, but amyloid load
      increased and organ function deteriorated in most of those whose SAA was
      persistently above 50 mg/L. Estimated survival at 10 years was 90% in patients
      whose median SAA was under 10 mg/L, and 40% among those whose median SAA exceeded
      this value (p=0.0009). INTERPRETATION: Although isolated amyloid fibrils are
      stable in vitro, AA amyloid deposits exist in a state of dynamic turnover, and
      outcome is favourable in AA amyloidosis when the SAA concentration is maintained
      below 10 mg/L. The potential for amyloid to regress and for the function of
      amyloidotic organs to recover support therapeutic strategies to decrease the
      supply of amyloid fibril precursor proteins in amyloidosis generally.

PMID- 11454374
TI  - Association between erythromycin resistance and ability to enter human
      respiratory cells in group A streptococci.
AB  - BACKGROUND: An increase in erythromycin resistance rates among group A
      streptococci has been reported in some European countries. These bacteria, long
      thought to be extracellular pathogens, can be efficiently internalised by, and
      survive within, human cells of respiratory-tract origin. Macrolide antibiotics
      enter eukaryotic cells, whereas beta-lactams are essentially confined to the
      extracellular fluid. A protein encoded by gene prtF1 is required for efficient
      entry of group A streptococci into epithelial cells. We investigated isolates of
      group A streptococci from children with pharyngitis in Italy for the presence of
      prtF1 and cell-invasion efficiency. METHODS: We investigated 74 erythromycin
      resistant and 52 erythromycin-susceptible isolates collected throughout Italy in
      1997-98 from children with pharyngitis. Erythromycin-resistance phenotypes
      (constitutive, inducible, and M) were assessed by the triple-disc test and
      resistance determinants (ermB, ermTR, and mefA) by PCR. All strains were examined
      for the presence of prtF1 by PCR and for their ability to enter cultured human
      respiratory cells. FINDINGS: The proportion of prtF1-positive strains was
      significantly higher among erythromycin-resistant than susceptible strains (66
      [89%] vs 11 [21%]; difference 68% [95% CI 52-84]). All erythromycin-resistant
      strains without prtF1 were of the M phenotype. The proportion of highly cell
      invasive isolates (invasion efficiency >10%) was significantly higher among
      erythromycin-resistant than among susceptible strains (59 [80%] vs five [10%];
      difference 70% [57-83]). INTERPRETATIONS: The unsuspected association between
      erythromycin resistance and cell invasiveness in group A streptococci raises
      serious concern. Strains combining erythromycin resistance and ability to enter
      human respiratory-tract cells may be able to escape both beta-lactams by virtue
      of intracellular location and macrolides by virtue of resistance.

PMID- 11454376
TI  - Postcremation diagnosis from an electric shaver.

PMID- 11454377
TI  - Spinal-cord involvement in diabetic peripheral neuropathy.
AB  - The pathogenesis of diabetic distal symmetrical polyneuropathy (DSP) is poorly
      understood but there is some evidence that the disease process might extend
      beyond peripheral nerves. We used magnetic-resonance imaging to measure spinal
      cord cross-sectional area in diabetic patients with and without DSP and in
      healthy controls. There were significant differences in cord area between the
      groups at C4/5 and T3/4 (p=0.004 and p=0.033, respectively), with a smaller cord
      area in those with DSP compared with controls (p=0.001 and p=0.016 for C4/5 and
      T3/4, respectively). These results indicate that DSP is not simply a disease of
      the peripheral nerve and that there is substantial involvement of the spinal
      cord.

PMID- 11454378
TI  - Emergency treatment of neonatal hyperammonaemic coma with mild systemic
      hypothermia.
AB  - An infant aged 3 days presented with hyperammonaemic coma and seizures, which
      were found to be a result of a urea-cycle defect. Haemofiltration, alternative
      pathway metabolites, and glucose and insulin failed to lower the plasma ammonia
      concentration below 2000 micromol/L. The infant was then cooled to a rectal
      temperature of 34 degrees C for 48 h and put on haemofiltration for 12 h. Plasma
      ammonia fell to around 100 micromol/L and remained at this concentration after
      haemofiltration. He roused from his coma, breathed spontaneously, and resumed
      bottle feeding. Hypothermia may be therapeutic in such instances of metabolic
      coma because it lowers the enzymatic rate of production of the toxin while non
      enzymatic methods remove the toxin.

PMID- 11454379
TI  - Evidence for a cerebral effect of the hepatitis C virus.
AB  - Patients with hepatitis C virus (HCV) infection frequently complain of symptoms
      akin to the chronic fatigue syndrome and score worse on health-related quality of
      life indices than matched controls. We address the hypothesis that HCV itself
      affects cerebral function. Using proton magnetic-resonance spectroscopy we have
      shown elevations in basal ganglia and white matter choline/creatine ratios in
      patients with histologically-mild hepatitis C, compared with healthy volunteers
      and patients with hepatitis B. This elevation is unrelated to hepatic
      encephalopathy or a history of intravenous drug abuse, and suggests that a
      biological process underlies the extrahepatic symptoms in chronic HCV infection.

PMID- 11454380
TI  - Effects of fenofibrate and gemfibrozil on plasma homocysteine.
AB  - Fenofibrate increases plasma homocysteine. Because the concentration of plasma
      homocysteine depends on renal function, we postulate that increases in plasma
      homocysteine are a result of the known impairment of renal function caused by
      fenofibrate. Gemfibrozil, another fibrate, does not affect renal function. In a
      crossover study we tested whether gemfibrozil would raise homocysteine. 22
      patients who had hypertriglyceridaemia were given 900 mg gemfibrozil or 200 mg
      fenofibrate daily for 6 weeks. Lipids were altered similarly, but homocysteine,
      creatinine, and cystatin C were raised by fenofibrate but not by gemfibrozil (p
      for differences between treatment effects: 0.007, 0.006, and 0.040,
      respectively). We propose gemfibrozil should be the fibrate of choice.

PMID- 11454381
TI  - Agency condemns "near-total neglect" of Angolans.

PMID- 11454385
TI  - Endogenously produced cannabinoids and liver cirrhosis.

PMID- 11454386
TI  - Counselling can help to reduce second-hand smoke in the home.

PMID- 11454387
TI  - Could Pneumocystis carinii have a role in sudden infant death syndrome?

PMID- 11454388
TI  - Tobacco's long-time adversary takes on Tinseltown.

PMID- 11454389
TI  - UK to embrace private-sector involvement in NHS?

PMID- 11454390
TI  - Polls indicate American public's acceptance of stem-cell research.

PMID- 11454394
TI  - Sao Paulo's controversial public-private partnership ends.

PMID- 11454395
TI  - Argentina to crack down on pharmaceutical black market.

PMID- 11454398
TI  - Irish Ombudsman finds medical records "atrocious".

PMID- 11454399
TI  - How immunology is reshaping clinical disciplines: the example of haematology.
AB  - Haematology represents a prime example of how rapidly immunology is moving
      towards the bedside. The diagnosis of blood disease has been modified by the
      "cluster of differentiation" (CD) nomenclature of leucocyte surface antigens, and
      the molecular genetics of the immune system has had a major effect on the
      diagnosis and treatment of blood malignancies. Lymphoid tumours represent a
      fertile area of interaction between immunology and haematology: B-cell
      malignancies are associated with dysregulation of the immune system, and antigen
      exposure might have an important role in the development of lymphoid malignant
      clones that interact with the microenvironment to avoid apoptosis and acquire
      better growing conditions. Understanding the pathophysiology of immune-mediated
      blood diseases has paved the way to the successful use of immunosuppressive
      agents, and the unravelling of the mechanisms of lymphocyte signal transduction
      and the relations between lymphocyte activation and apoptosis are allowing new
      therapeutic approaches. Paradoxically, lymphoid tumours are an excellent model to
      test the efficacy of manipulating the immune system for the purpose of tumour
      eradication.

PMID- 11454400
TI  - Common hereditary cancers and implications for primary care.
AB  - The identification of genes that place individuals at high risk of breast,
      ovarian, and colorectal cancer has greatly advanced our understanding of cancer
      predisposition over the past decade. This knowledge has received much attention
      from the media, and referrals to geneticists and surgeons, and requests for
      genetic testing, have risen. We review the published evidence for the management
      of people at increased risk of hereditary cancers, to draw attention to areas of
      uncertainty and to discuss implications for primary care. We focus on common
      inherited cancers, since they will have the greatest effect on clinical practice
      over the next decade. Cancer genetics offers a model of how information on the
      genetics of other common diseases could affect primary care in the future.
      Strategies to support the integration of genetic medicine in primary care are
      needed to enable primary-care practitioners to identify individuals at raised
      genetic risk and to reassure patients for whom genetic testing and increased
      surveillance offer little benefit.

PMID- 11454401
TI  - Adjusting Europe's drug regulation to public health needs.

PMID- 11454406
TI  - Wearing a watch can endanger your life.

PMID- 11454408
TI  - Developmental changes of synaptojanin expression in the human cerebrum and
      cerebellum.
AB  - Synaptojanin is a highly abundant polyphosphoinositide phosphatase in nerve
      terminals, and has been thought to play roles in clathrin-mediated synaptic
      vesicle endocytosis and signaling. In order to determine the broader role of
      synaptojanin in the central nervous system, we examined synaptojanin expression
      in the cerebrum and cerebellum from the fetal to the adult period by means of
      immunohistochemical and Western blot analyses. Immunohistochemistry consistently
      revealed the localization of synaptojanin in Cajal--Retzius cells, cortical plate
      neurons, subplate neurons, intermediate neurons, germinal matrix cells and the
      ventricular neuroepithelium of the fetal cerebrum. In the fetal cerebellum,
      synaptojanin immunoreactivity was localized in the external granular cell layer,
      Purkinje cell layer neuropil, cytoplasm of Purkinje cells and internal granular
      cells. The immunoreactivity in these structures was decreased around birth. After
      birth, the synaptojanin immunoreactivity of cortical neurons in the cerebrum,
      Purkinje cell layer neuropil, and internal granular cells and Purkinje cells in
      the cerebellum increased and reached a plateau after 11 years of age. These
      results were consistent with the intensity observed on Western blot analysis.
      These developmental changes of synaptojanin suggest a broader role in not only
      synaptic vesicle recycling, but also the regulation of neuronal migration and
      synaptogenesis in the fetal cerebrum and cerebellum.

PMID- 11454409
TI  - Calbindin-D28k and calretinin immunoreactive neurons in the olfactory bulb of the
      musk shrew, Suncus murinus.
AB  - The distribution, morphological features, and postnatal development of calbindin
      D28k (CB) and calretinin (CR) immunoreactive neurons in the main olfactory bulb
      (MOB) of the musk shrew, Suncus murinus, were studied by immunostaining to
      determine the degree of colocalization of CB and CR, and the relationship of CB
      and CR to neuron development in the MOB of animals of the order Insectivora. In
      adults, CB-positive neurons were identified as periglomerular and perinidal cells
      in the periglomerular region, as superficial short-axon cells in the external
      plexiform layer, and as four types of interneurons (Cajal, horizontal, Golgi, and
      bitufted cells) in the mitral cell, internal plexiform, and granule cell layers.
      CR-positive neurons were identified as projection neurons (tufted and mitral
      cells) and interneurons (periglomerular, perinidal, and granule cells). On
      postnatal days 1 and 3, CB-positive neurons revealed numerous processes finely
      arborized near the somata, and were morphologically unidentifiable. At the same
      time, CR-positive neurons were identified as young periglomerular and granule
      cells, and as migrating bipolar cells extending leading processes with growth
      cones in each layer of the MOB and the subependymal layer between the anterior
      lateral ventricle and the center of the MOB. On postnatal day 28, mature CB
      positive and CR-positive interneurons were distributed in their corresponding
      layers, whereas migrating CR-positive bipolar cells were rarely detected. No
      cells colocalized CB and CR. The results suggest that perinidal cells in the
      shrew MOB may develop postnatally, together with glomerular and granule cells. We
      suggest that CB is associated with mechanisms of the outgrowth of neuronal
      processes, whereas CR is involved in mechanisms of cell migration and outgrowth
      of neuronal processes, in some types of neurons in the developing stage of the
      shrew MOB.

PMID- 11454410
TI  - Recurrent neonatal seizures: relationship of pathology to the
      electroencephalogram and cognition.
AB  - Seizures in preterm infants are associated with a high risk of neurological
      sequelae. In the neonatal rat recurrent seizures have been associated with long
      term changes in cerebral excitability and cognition as well as sprouting of mossy
      fiber terminals in the granule cell layer of the dentate gyrus and hippocampal
      CA3 subfield. To evaluate the relationship between seizure-induced morphological
      changes and cognitive function we subjected newborn rats to 55 seizures with
      flurothyl during the first 12 days of life. During adolescence rats with prior
      recurrent seizures were compared with controls in electroencephalographic power
      and performance in the Morris water maze and open field test. Rats subjected to
      recurrent seizures had marked impairment in water maze performance and never
      reached the level of learning seen in controls despite a total of 54 trials.
      Recurrent seizures were also associated with an overall reduction in spectral
      power which was most pronounced in the theta range. On histological examination
      rats with recurrent neonatal seizures had sprouting of mossy fiber terminals in
      CA3 and the granule cell layer of the dentate gyrus without any accompanying cell
      loss. Sprouting in CA3, but not the granule cell layer of the dentate gyrus,
      correlated with water maze performance. This study demonstrates that recurrent
      neonatal seizures can result in profound impairment of water maze performance and
      reduction of electroencephalographic power despite the lack of discernible cell
      loss and that this cognitive impairment correlates with mossy fiber sprouting in
      CA3.

PMID- 11454411
TI  - Identification of a developmental gradient of estrogen receptor expression and
      cellular localization in the developing and adult female rat primary
      somatosensory cortex.
AB  - Immunohistochemistry was used to investigate the spatiotemporal distribution of
      estrogen receptor alpha and beta (ER alpha, ER beta) in the posteromedial barrel
      subfield (PMBS) of the cerebral cortex in developing and adult female rats.
      Counting of immunopositive cells in predefined areas from each layer of the PMBS
      showed that at PN3, ER alpha immunoreactivity (IR) was present in every cell,
      whereas ER beta-IR was not detected. At PN6, about 59% of the cells were ER alpha
      immunopositive and low levels of ER beta-IR were observed in scattered cells. At
      PN18 the proportion of ER alpha-IR cells decreased to 49%; however, ER beta-IR
      became widespread and was detected in 39% of cells. By PN25 only faint ER alpha
      IR was observed and in the adults ER alpha-IR was not detected. In contrast, at
      PN25 and in adults, ER beta-IR was detected in about half the cells of the PMBS.
      Regarding the cellular localization of ER-IR, at PN3 an outside-in gradient of
      cytoplasmic to nuclear localization of ER alpha-IR was observed. At PN18 and in
      adults ER beta-IR was preferentially localized to the nucleus of principal
      neurons, and to the cytoplasm of small, stellate-shaped interneurons. Together,
      these observations reveal a developmental transition of ER expression in the
      PMBS; ER alpha is expressed during early development, ER alpha and ER beta are co
      expressed at later developmental times, and only ER beta is expressed in adults.
      These changes in ER expression and localization suggest that ER alpha and ER beta
      may play important, but different roles in the formation and function of the PMBS
      region of the primary somatosensory cortex.

PMID- 11454412
TI  - The expression of mRNAs for the proteasome complex is developmentally regulated
      in the rat mesencephalon.
AB  - The proteasome is a large protease complex that recognizes, unfolds and degrades
      ubiquitinated proteins. Evidence is now accumulating that the ubiquitin
      proteasome system may play an important role in neuronal apoptosis. However,
      little is known about the involvement of the proteasome in neuronal death in
      vivo, and there has been no prior analysis of the developmental expression of
      proteasome subunits in brain during periods of natural and inducible apoptotic
      death. We therefore studied the mRNA expression levels, using Northern analysis,
      of a subunit from each of the three key components of the proteasome in the rat
      mesencephalon from E21 through development and in adulthood. We measured mRNA
      expression for RC6 (a subunit of 20S), p112 (a subunit of 19S) and PA28-alpha (a
      subunit of 11S). The expression of PA28-alpha in rat mesencephalon was highest at
      the earliest times studied, and then decreased at PND 21, 28 and adult, in
      comparison to E21 (P<0.05) and PND 2, 4 and 7 (P<0.01). The expression of RC6 was
      lower in adult in comparison to PND 2, 4 and 21 (P<0.05) and PND 14 (P<0.01).
      There were no significant differences in the mRNA levels of p112 at various times
      studied. In situ hybridization at PND 7 indicated that all the subunits studied
      are particularly abundant in the SNpc. Thus, PA28-alpha and RC6 are
      developmentally regulated, and they may therefore play a role in developmental
      cell death or differentiation in neurons of the SN.

PMID- 11454413
TI  - Gastrointestinal projection maps of the vagus nerve are specified permanently in
      the perinatal period.
AB  - The vagal innervation of the proximal gastrointestinal (GI) tract is lateralized.
      To determine whether this pattern is specified as early as the perinatal period,
      neonatal rat pups were given unilateral cervical vagotomies. Separate groups
      received (1) transections below the left nodose ganglion, (2) left cervical
      resections that included removal of the nodose ganglion, or (3) sham surgeries.
      At 4 months of age, each animal's vagal afferent projections from the unoperated
      side were mapped by injecting the nodose with WGA-HRP, preparing the stomach as
      wholemounts, and processing the tissue with tetramethyl benzidine. The two types
      of vagal afferent endings in GI smooth muscle, namely intraganglionic laminar
      endings and intramuscular arrays, were surveyed separately, and their regional
      distributions were mapped. Changes in the nucleus of the solitary tract (NST) and
      dorsal motor nucleus of the vagus (DMNX) were assessed with cell counts and area
      measurements. Neonatal loss of the vagus innervating one side of the GI tract,
      with or without ganglionectomy, did not cause the unoperated vagus to sprout to
      the denervated side. In addition, removal of the projections to the one side of
      the target organ did not produce a reorganization of the projection maps of the
      unoperated vagus within its normal or ipsilateral wall of the GI tract. Although
      the regional patterns of the unoperated ipsilateral vagus were not affected, the
      packing densities of both types of afferents supplied by this trunk were
      moderately reduced. The DMNX of the vagotomized side displayed extensive
      (approximately 83%) neuronal loss; the DMNX on the unoperated side as well as the
      NST on both sides exhibited limited (approximately 20--25%) losses. The lack of a
      peripheral projection field reorganization -- except for a moderate down
      regulation -- after complete unilateral denervation suggests that both the
      laterality and the afferent terminal phenotypes (or target tissues) of the vagus
      in the proximal GI tract are specified by postnatal day one in the rat. The
      present results, taken together with other observations, also suggest that three
      different combinations of signals orchestrate the commitments of vagal afferents
      respectively to (1) the side of the organ, (2) the region within the organ wall,
      and (3) the accessory and innervated tissues that complex with the fully
      differentiated ending.

PMID- 11454414
TI  - Sexual dimorphism in the brain metabolic response to prenatal cocaine exposure.
AB  - The effects of prenatal cocaine exposure on the metabolic function of major
      central neuronal systems in the periweanling rat are reported in this study.
      Pregnant Sprague--Dawley rats were administered cocaine at either 30 or 60 mg/kg
      or the vehicle from gestation day (G) 8 through 22 via daily gastric intubation.
      Since prenatal cocaine has been shown to alter behavior in weanling rats, brain
      functional activity was quantified using the deoxyglucose method in male and
      female 21-day-old offspring (one of each gender/litter). Cocaine's effects were
      most significant within the limbic system where a three-way interaction between
      cocaine treatment, sex and brain region was seen. Within the limbic system, two
      regions, the rostral accumbens and the diagonal band of Broca showed reductions
      in metabolic activity in the exposed male offspring compared to the control
      offspring while no changes were seen in females. At more caudal levels of the
      forebrain, the accumbens (at the level of 1.2 micro rostral to Bregma) and septum
      showed cocaine-induced reductions in metabolism which were not dependent upon the
      sex of the animal. Metabolism within the hypothalamus also tended to show a
      significant interaction between treatment, gender and brain region (P=0.06). Two
      regions, including the ventromedial nucleus and lateral hypothalamic area, were
      metabolically depressed in the males alone while three other regions; the
      dorsomedial, arcuate, and medial preoptic nuclei were also metabolically
      depressed in the treated groups collapsed across gender. There were no
      significant treatment or sex-related effects or interactions within the sensory
      and motor systems. Chronic prenatal cocaine exposure reduced metabolism
      significantly in a restricted portion of the forebrain, the mesocortical-limbic
      system, particularly in regions associated with the medial forebrain bundle.
      These reductions were seen primarily in males while some regions showed changes
      which were independent of the sex of the animal. These cocaine-induced effects
      resembled, to a great extent, those seen in similarly-treated males examined as
      adults. The data emphasize that cocaine use during a restricted period of early
      pregnancy depresses function within limbic and hypothalamic regions and that many
      of these effects are sexually dimorphic in nature.

PMID- 11454415
TI  - Spectrins in developing rat hippocampal cells.
AB  - We studied the spectrins in developing hippocampal tissue in vivo and in vitro to
      learn how they contribute to the organization of synaptic and extrasynaptic
      regions of the neuronal plasma membrane. beta-Spectrin, but not beta-fodrin or
      alpha-fodrin, increased substantially during postnatal development in the
      hippocampus, where it was localized in neurons but not in astrocytes.
      Immunoprecipitations from neonatal and adult hippocampal extracts suggest that
      while both beta-spectrin and beta-fodrin form heteromers with alpha-fodrin,
      oligomers containing all three subunits are also present. At the subcellular
      level, beta-fodrin and alpha-fodrin were present in the cell bodies, dendrites,
      and axons of pyramidal-like neurons in culture, as well as in astrocytes. beta
      Spectrin, by contrast, was absent from axons but present in cell bodies and
      dendrites, where it was organized in a loose, membrane-associated meshwork that
      lacked alpha-fodrin. A similar meshwork was also apparent in pyramidal neurons in
      vivo. At some dendritic spines, alpha-fodrin was present in the necks but not in
      the heads, whereas beta-spectrin was present at significant levels in the spine
      heads. The presence of significant amounts of beta-spectrin without an
      accompanying alpha-fodrin subunit was confirmed by immunoprecipitations from
      extracts of adult hippocampus. Our results suggest that the spectrins in
      hippocampal neurons can assemble to form different membrane-associated structures
      in distinct membrane domains, including those at synapses.

PMID- 11454416
TI  - Neither peripheral nerve input nor cortical NMDA receptor activity are necessary
      for recovery of a disrupted barrel pattern in rat somatosensory cortex.
AB  - Elevating cortical serotonin (5-HT) in rats from postnatal day (P-) 0 to P-6 by
      administering the monoamine oxidase (MAO(A)) inhibitor, clorgyline, produces a
      dose-dependent spectrum of effects on rat somatosensory organization, ranging
      from enlarged with indistinct septa to a complete lack of vibrissae-related
      patterns. However, if clorgyline treatment is stopped on P-6, a qualitatively and
      quantitatively normal vibrissae-related pattern of thalamocortical afferents
      appears in somatosensory cortex (S-I) on P-10. We employed high performance
      liquid chromatography (HPLC), infraorbital nerve (ION) transection, N-methyl-D
      aspartate (NMDA) receptor blockade, 1,1'-dioctadecyl-3,3,3"3'
      tetramethylindocarbocyanine perchlorate (DiI) labeling of thalamic afferents, and
      CO histochemistry to determine whether peripheral nerve input and/or cortical
      NMDA receptor activity were required for the recovery of vibrissae-related
      patterns in clorgyline-treated animals. Clorgyline administration from P-0 to P-6
      produced a 1589.4+/-53.3% increase in cortical 5-HT over control animals on P-6
      and a 268.8+/-6.3% elevation over controls at P-10. Postnatal day 6 pups had
      significantly altered vibrissae-related patterns in S-I following 6 days of
      clorgyline treatment but by P-10, the characteristic vibrissae-related patterns
      were restored. Neither transection of the ION nor application of the NMDA
      antagonist, DL-2-amino-5-phosphonovaleric acid (APV), to the cortices of P-6 pups
      that were treated with clorgyline from birth had any significant effect on the
      recovery of the vibrissae-related patterns by P-10. These results indicate that
      neither peripheral nerve input nor cortical NMDA receptor activity are necessary
      for the restoration of cortical vibrissae-related patterns in rats that have
      sustained transient elevations of 5-HT.

PMID- 11454417
TI  - The critical window of brain development from susceptive to insusceptive. Effects
      of clomipramine neonatal treatment on sexual behavior.
AB  - The immature brain is much more sensitive to abnormal experience, particularly
      sleep deprivation, drug exposure, and maternal separation. The critical time
      period during which features in the brain's susceptibility to such experience
      change, however, has not yet been determined. In previous studies on rats, we
      found that neonatal treatment with clomipramine (CLI) during postnatal days 8--21
      (P8-21) produced behavioral and physiological abnormalities in adult rats that
      resembled the abnormalities found in human endogenous depression. The objective
      of the present study is to determine (1) the critical (more specifically, the
      latest) time frame in which CLI treatment will produce adult depression and (2)
      the shortest treatment window during which CLI can induce adult depression. Male
      rats were neonatally treated with CLI (20 mg/kg, sc) twice daily or with an
      equivolume of saline. The treatment windows were P12--17, P14--20, P16--22, and
      P12--15. Six variables, including number of mounts, intromission, ejaculation,
      mount latency, ejaculation latency, and post-ejaculation interval, were measured
      visually between the ages of 4 and 5 months. Rats treated with CLI showed
      significant sexual impairment in treatment windows P12--17 and P14--20 and slight
      sexual deficiency in the short window P12--15. No significant sexual impairment
      was found in window P16--22. We concluded that P14--20 was the latest window
      during which CLI treatment produces adult sexual deficiency and that 6 days might
      be the shortest treatment window to produce significant behavior abnormalities.

PMID- 11454418
TI  - Effects of estrogen and neurotransmitters on the primary cultures of tilapia
      brain from different ages.
AB  - The effects of estrogen and neurotransmitters on the proliferation of brain cells
      were investigated in the primary cultures of tilapia brain from different ages.
      Treatment of brain cells that were cultured on day 1, 3, 5, 7, 10, 30, and 180
      posthatching with serotonin (5-HT), resulted in a significant increase of the
      Brdu(+)-cell number. By contrast, norepinephrine (NE) resulted in a significant
      decrease and gamma-aminobutyric acid (GABA) had no effect. 17 beta-Estradiol
      (E(2)) significantly increased the Brdu(+)-cell number when the brain cells were
      cultured after 5 days of age, but had no effect when cultured on day 1 or 3 of
      age. These results indicate that the proliferation of brain cell is enhanced by 5
      HT at each stage. This effect is mimicked by E(2) when given after 5 days of age.
      Conversely, NE has an effect to depress the proliferation of brain cells.
      Whereas, GABA has no effect.

PMID- 11454419
TI  - Migration and differentiation of Nkx-2.2+ oligodendrocyte progenitors in
      embryonic chicken retina.
AB  - During early neural development, the Nkx-2.2 homeobox gene is initially induced
      in the ventral ventricular zone of the central nervous system (CNS). At later
      stages, Nkx-2.2+ cells migrate away into the surrounding regions and co-express
      several oligodendrocyte marker genes. Here we report that Nkx-2.2+ cells also
      migrate into the avian retina from the optic nerve. These Nkx-2.2+ cells are
      specifically labeled by the early oligodendrocyte markers PDGFR alpha, O4 and
      GalC, but not the microglial marker QH1 or neuron-specific marker MAP-2. These
      observations provide further evidence that Nkx-2.2 is selectively expressed in
      migratory oligodendrocyte progenitor cells and that retina oligodendrocytes
      originate from the ventral diencephalon.

PMID- 11454420
TI  - Selective cholinergic denervation inhibits expression of long-term potentiation
      in the adult but not infant rat hippocampus.
AB  - The present study assessed the role of the cholinergic systems on the expression
      of perforant path long-term potentiation (LTP) in rat hippocampal slices from the
      infant and adult brain. To denervate the cholinergic systems, 192 IgG--saporin
      was injected into the lateral ventricle of the infant (2-weeks-old) and adult (6
      weeks-old) rat brain. There, choline acetyltransferase-immunoreactive fibers were
      barely detectable 2 weeks and 2 months after injection for both the groups. For
      the infant rats, perforant path LTP was not affected by selective cholinergic
      denervation; the probability of LTP development was 0.83 (five out of six slices)
      and 0.78 (seven out of nine slices) at 2 weeks and 2 months later in 192 IgG-
      saporin-treated slices, as compared with 0.83 at each period in control saline
      treated slices. In contrast, the expression of the LTP was blocked by selective
      cholinergic denervation for the adult rats; the probability of LTP development
      was 0 (zero out of 10 slices) and 0.38 (three out of eight slices) at 2 weeks and
      2 months later in 192 IgG--saporin-treated slices, as compared with 0.8 (eight
      out of 10 slices) and 0.83 (five out of six slices) at each period in control
      saline-treated slices. The results of the present study thus suggest that the
      cholinergic systems play a crucial role in the expression of LTP in the adult
      brain and that the denervated systems in the infant brain could be compensated by
      the sprouting of non-cholinergic fibers.

PMID- 11454421
TI  - Changes in gene expression during progression of ovarian carcinoma.
AB  - The molecular events leading to the development and progression of serous ovarian
      carcinoma are not completely understood. We performed a large scale survey for
      the identification of differentially expressed genes in serous ovarian carcinoma
      by using cDNA array analysis. Differences in gene expression between serous
      adenocarcinoma and benign serous adenoma, and between advanced and/or moderately
      or poorly differentiated and local, highly differentiated serous adenocarcinoma
      were assessed. The most striking difference between adenocarcinoma and benign
      adenoma was upregulation of RHOGDI2 in the carcinomas irrespective of the
      clinical tumor stage. Other changes in carcinoma were upregulation of MET and Ne
      dlg, and downregulation of HGFAC, desmin, and PDGFA. The most prominent
      differences between advanced and local adenocarcinoma were upregulation of
      COL3A1, CFGR, and MET in advanced carcinoma, and downregulation of HGFAC, FZD3,
      and BFL1 in the same tumors. In conclusion, significant differences were found in
      the gene expression between benign and malignant serous ovarian tumors, and
      between local, highly differentiated and advanced and/or moderately or poorly
      differentiated serous adenocarcinomas. The differentially expressed genes may be
      related to the carcinogenesis and progression of the malignant growth.

PMID- 11454422
TI  - Cytogenetic aberrations in adult acute lymphocytic leukemia: optimal technique
      may influence the results.
AB  - The aim of the present study was to analyse the distribution of cytogenetic
      aberrations in adult ALL in a population based material and compare the results
      with literature data. Forty-one patients were diagnosed during a 12-year period.
      The age varied between 14 and 82 (mean 37, median 32). Thirty-two patients were
      cytogenetically investigated and in all cases analysable metaphases were obtained
      (range 10-29, mean 24, median 25, success rate: 100%). Nine (28%) patients had a
      T-phenotype and 23 (72%) had a pre-B phenotype. High hyperdiploidy was found in
      four patients (13%). Hypodiploidy was found in 5 patients (16%), 10 (31%) had a
      pseudodiploid chromosome mode and four (13%) showed low hyperdiploidy (chromosome
      mode 47-51). Chromosomes 10 and 18 were most frequently involved in numerical
      aberrations. Structural aberrations most frequently involved chromosomes 6, 9 and
      22. t(9;22) was seen in six cases (19%), del(6q) in five cases (16%) and der(9p)
      in five cases (16%). High hyperdiploid clones, which are associated with a
      favorable prognosis, were found with the same frequency as in other studies. The
      frequency of t(9;22) was 19% in our study, others have found frequencies between
      11% and 30%. Compared to previously published studies our patients with t(9;22)
      were younger. Furthermore, those with del(6q) were older, showing a median age
      equivalent to the patient group as a whole. The differences between our data and
      previously published studies may be explained by population-based derived data
      and especially by an optimal technique in obtaining metaphases.

PMID- 11454423
TI  - Isochromosome (17)(q10) as the sole structural chromosomal rearrangement in a
      case of botryoid rhabdomyosarcoma.
AB  - We describe a case of botryoid rhabdomyosarcoma with the karyotype
      53,XX,+2,+5,+8,+12,+13, i(17)(q10),+19,+20. Only two cytogenetically analyzed
      cases of this tumor were previously reported and structural chromosomal
      abnormalities in each tumor were different.

PMID- 11454424
TI  - Cytogenetic characterization of six malignant peripheral nerve sheath tumors:
      comparison of karyotyping and comparative genomic hybridization.
AB  - We analysed six malignant peripheral nerve sheath tumors (MPNSTs) from four
      patients using metaphase preparations and compared the results with those
      obtained by using comparative genomic hybridization (CGH). All six tumors showed
      structural and numerical chromosomal aberrations, mostly of chromosomes 1, 5, 7
      10, 14-17, 19, 21, and 22. The number of chromosomes per tumor cell ranged from
      42 to 104. We could not find a recurrent specific pattern of structural changes
      after comparing the MPNSTs of different patients. However, aberrations of
      different tumors from the same patient were nearly identical. In the four
      patients, we found a total of 117 breakpoints, mostly in 21q11.2 (seven times),
      in 8q11.2 and 14q10 (six times each), in 5q11.2 and 15q26 (four times each), in
      8p11.2, 10q11.2, 16q22, 19q13.3, and 22q10 (three times each). In three MPNSTs,
      double minute chromosomes (dmin) we detected with metaphase investigations and
      high-level amplifications by using CGH, respectively. C-MYC gene amplification
      and loss of the P53 gene could be ruled out by locus-specific probes for the
      common gain of 8q and for losses of 17p. When comparing the CGH results with
      those of karyotyping an overlap in the most frequent gains in 7q, 8q, 15q, and
      17q was observed. However, we found more frequent losses in 19q in the metaphase
      investigations.

PMID- 11454425
TI  - Chromosomal aberrations in malignant gastrointestinal stromal tumors: correlation
      with c-KIT gene mutation.
AB  - Gastrointestinal stromal tumors (GISTs) are distinctive, KIT positive mesenchymal
      neoplasms. The genetic alterations leading to the malignant behavior of these
      tumors are not well known. In this study, we looked for recurrent numerical
      chromosomal changes, which may be associated with malignant GISTs, using
      interphase fluorescence in situ hybridization (FISH). Fourteen malignant primary
      tumors and two intra-abdominal recurrences were analyzed. Nine benign tumors were
      studied for comparison. In all cases, the presence of mutations in exons 9, 11
      and 13 of the KIT gene were evaluated. Sixteen centromeric enumeration probes
      (CEP) for chromosomes 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 15, 16, 17, 18, and X
      and three locus specific probes (LSI) for 22q11.2 (BCR-locus), 13q14 (RB1-locus)
      and 14q32 (IgH-locus) were used. The most common changes seen in malignant GISTs
      were losses of 14q32 and 22q11. However, these changes were commonly detected in
      benign tumors and represent early changes related to the pathogenesis of GISTs.
      Losses of chromosomes 1 and 9 were the only recurrent numerical changes seen
      exclusively in malignant GISTs. Other recurrent numerical changes seen
      predominantly in malignant tumors were gain of chromosome 8 and losses of
      chromosomes 7 and 15. The concurrent loss of chromosome 7 and gain of chromosome
      8 (in 4 cases) was never seen together with loss of chromosomes 9 or 15 and only
      once with loss of chromosome 1. Mutations in KIT were found in the majority of
      malignant GISTs (64%) confirming a previously shown correlation between presence
      of such mutations and malignancy. KIT mutations were seen in four of five
      malignant GISTs with loss of chromosome 9, but only in one of four malignant
      tumors with loss of chromosome 1. These observations may reflect the different
      pathways leading to malignant transformation of GISTs.

PMID- 11454426
TI  - Amplification of hypoxia-inducible factor 1alpha gene in prostate cancer.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates the
      expression of genes associated with adaptation to reduced oxygen pressure.
      Increased expression of HIF-1alpha gene (HIF1A) has been found in the majority of
      prostate carcinomas. In addition, the PC-3 prostate cancer cell line has been
      shown to express the gene even under normoxic conditions. By comparative genomic
      hybridization (CGH), we have earlier shown that the PC-3 cell line contains a
      high-level amplification in the chromosomal region harboring the HIF1A gene.
      Here, we first fine mapped the gene to locus 14q23 by fluorescence in situ
      hybridization (FISH). The gene was then shown to be highly amplified in the PC-3
      cell line. Subsequently, the copy number of the HIF1A gene was studied in 5 other
      prostate cancer cell lines (LNCaP, DU-145, NCI-H660, Tsu-Pr, JCA-1) and in 117
      prostate tumors representing both hormone-dependent and -refractory disease as
      well as primary and metastatic lesions. No high-level amplifications of the HIF1A
      gene were found. Additional copies of the gene were seen in all of the cell lines
      and in 36% of the tumors. There was no association between the tumor type and the
      copy number alterations of the gene. In conclusion, high-level amplification of
      the HIF1A gene may explain the overexpression of the gene in the PC-3 prostate
      cancer cell line. However, such high-level amplification seems to be very rare in
      prostate cancer.

PMID- 11454427
TI  - Derivative (1;18)(q10;q10): a recurrent and novel unbalanced translocation
      involving 1q in myeloid disorders.
AB  - We report two cases of hematological malignancies, comprising a case of
      myelodysplastic syndrome (MDS) that rapidly evolved into acute myeloid leukemia,
      and a case of myeloproliferative disorder (MPD), in which der(1;18)(q10;q10) was
      found as the sole acquired karyotypic abnormality. This observation indicates
      that the unbalanced translocation is a recurrent aberration in myeloid disorders.
      To the best of our knowledge, centromeric fusion between long arms of chromosomes
      1 and 18, leading to a normal chromosome 18 substituted with a der(1;18)
      chromosome, is novel and has not been described in cancer. Mechanistically,
      either trisomy 1q or monosomy 18p that results from the translocation may
      potentially contribute to leukemogenesis. Finally, chromosomes with large
      constitutive heterochromatin bands such as chromosome 1 may be at risk of
      centromeric instability and be predisposed to centromeric fusion with other
      chromosomes.

PMID- 11454428
TI  - Chromosomal aberrations in Bloom syndrome patients with myeloid malignancies.
AB  - Bloom syndrome (BS) predisposes affected individuals to a wide variety of
      neoplasms including hematological malignancies. Thus far, cytogenetic findings in
      hematological neoplasms have been reported in only a few BS patients. We present
      the karyotypic findings in a BS patient diagnosed with acute myeloid leukemia
      (AML), FAB subtype M1, and a review of the literature, showing the preferential
      occurrence of total or partial loss of chromosome 7 in BS patients with AML or
      myelodysplastic syndromes (MDS).

PMID- 11454429
TI  - Beta-catenin activation through mutation is rare in rectal cancer.
AB  - Increased transcriptional activation through beta-catenin stabilization plays a
      central role in colorectal tumorigenesis. Alterations of phosphorylation sites
      within the CTNNB1 gene, which codes for beta-catenin has been reported to occur
      in about one-half of colorectal tumors without APC-gene mutations. We assessed
      the importance of mutations in the regulatory domain, located within exon 3 of
      CTNNB1, in 103 rectal carcinomas and correlated these data with presence of
      microsatellite instability, somatic frame-shift alterations of the TCF-4 gene,
      and APC-gene mutations in the tumors. No mutation was detected in exon 3 of the
      CTNNB1 gene and our results thus demonstrate that beta-catenin activation through
      mutation rarely contributes to the development of sporadic and microsatellite
      instability stable rectal cancer.

PMID- 11454431
TI  - Contributions of biological psychology to psychopathology.

PMID- 11454432
TI  - Behavioral and brain imaging studies of saccadic performance in schizophrenia.
AB  - Data are reviewed from a series of saccadic studies demonstrating that
      schizophrenia subjects have normal performance on some types, and abnormal
      performance on other types, of tasks. Normal refixation saccade characteristics
      and BOLD signal change among schizophrenia subjects suggest that basic saccade
      generating circuitry is functionally intact among these subjects. Schizophrenia
      patients and their relatives, however, demonstrate difficulty with saccadic
      inhibition, a function ostensibly mediated by DLPFC circuitry. We review
      additional evidence for saccadic inhibition being associated with prefrontal
      circuitry provided by EEG and fMRI data. Minimum norm analysis of EEG data
      suggests that dipolar activity preceding correct antisaccades occurred
      preferentially in prefrontal cortex. Furthermore, there is an indication from the
      fMRI data that prefrontal activity may be increased in normal, but not in
      schizophrenia, subjects during antisaccade tasks. These data suggest that a
      research program relying on multiple functional imaging technologies may be
      helpful for furthering our understanding of schizophrenia's essential
      neuropathology.

PMID- 11454433
TI  - Semantic disturbance in schizophrenia and its relationship to the cognitive
      neuroscience of attention.
AB  - We view schizophrenia as producing a failure of attentional modulation that leads
      to a breakdown in the selective enhancement or inhibition of semantic/lexical
      representations whose biological substrata are widely distributed across left
      (dominant) temporal and frontal lobes. Supporting behavioral evidence includes
      word recall studies that have pointed to a disturbance in connectivity
      (associative strength) but not network size (number of associates) in patients
      with schizophrenia. Paralleling these findings are recent neural network
      simulation studies of the abnormal connectivity effect in schizophrenia through
      'lesioning' network connection weights while holding constant network size.
      Supporting evidence at the level of biology are in vitro studies examining N
      methyl-D-aspartate (NMDA) receptor antagonists on recurrent inhibition;
      simulations in neural populations with realistically modeled biophysical
      properties show NMDA antagonists produce a schizophrenia-like disturbance in
      pattern association. We propose a similar failure of NMDA-mediated recurrent
      inhibition as a candidate biological substrate for attention and semantic
      anomalies of schizophrenia.

PMID- 11454434
TI  - Prospects for antidepressant drug discovery.
AB  - Recent socioeconomic analyses found that depression is a leading cause of
      disability and a major risk factor for development of other diseases. Moreover,
      on a world-wide scale depression is underdiagnosed and undertreated. Current
      antidepressant drugs have proven to be effective, but are burdened with slow
      onset of action and side effects. Above this, it is still unclear by which
      pharmacological mode of action they exert their clinical effects. Hypothesis
      driven research based upon the corticosteroid receptor hypothesis of depression
      has led to a novel concept focusing on brain neuropeptide receptors, specifically
      the corticotropin-releasing hormone (CRH) receptor as drug target. This treatise
      expands on this new development, its background and its promises including first
      clinical experiments. In the era of functional genomics, however, hypothesis
      driven research will be complemented by a new strategy that relies on a 'bottom
      up' search for new drug targets through screening techniques that range from the
      use of DNA microarrays, searches of compound libraries to behavioral screens of
      mouse mutants, just to name a few. In this sense, biotechnology opens up new
      chances for drug development through serendipity by providing new data bases on
      which systematic biological research in psychiatry and psychology can be
      conducted.

PMID- 11454435
TI  - Sleep and depression--results from psychobiological studies: an overview.
AB  - Disturbances of sleep are typical for most depressed patients and belong to the
      core symptoms of the disorder. Polysomnographic sleep research has demonstrated
      that besides disturbances of sleep continuity, in depression sleep is
      characterized by a reduction of slow wave sleep and a disinhibition of REM sleep,
      with a shortening of REM latency, a prolongation of the first REM period and
      increased REM density. These findings have stimulated many sleep studies in
      depressive patients and patients with other psychiatric disorders. In the
      meantime, several theoretical models, originating from basic research, have been
      developed to explain sleep abnormalities of depression, like the two-process
      model of sleep and sleep regulation, the GRF/CRF imbalance model and the
      reciprocal interaction model of non-REM and REM sleep regulation. Interestingly,
      most of the effective antidepressant agents suppress REM sleep. Furthermore,
      manipulations of the sleep-wake cycle, like sleep deprivation or a phase advance
      of the sleep period, alleviate depressive symptoms. These data indicate a strong
      bi-directional relationship between sleep, sleep alterations and depression.

PMID- 11454436
TI  - The somatic symptom paradox in DSM-IV anxiety disorders: suggestions for a
      clinical focus in psychophysiology.
AB  - Although DSM-IV criteria for anxiety disorders include physiological symptoms,
      these symptoms are evaluated exclusively by verbal report. The current review
      explores the background for this paradox and tries to demonstrate on theoretical
      and empirical grounds how it could be resolved, providing new insights about the
      role of psychophysiological measures in the clinic. The three-systems approach to
      evaluating anxiety argues that somatic measures as well as verbal and behavioral
      ones are indispensable. However, the low concordance between these domains of
      measurement impugns their reliability and validity. We argue that concordance can
      be improved by examining the relationship of variables less global than anxiety
      and by restriction to specific anxiety disorders. For example, recent evidence
      from our and other laboratories indicate a prominent role of self-reported and
      physiologically measured breathing irregularities in panic disorder. Nonetheless,
      even within a diagnosis, anxiety patients vary radically in which somatic
      variables are deviant. Thus, in clinical practice, individual profiles of
      psychological and physiological anxiety responses may be essential to indicate
      distinct therapeutic approaches and ways of tracking improvement. Laboratory
      provocations specific to certain anxiety disorders and advances in ambulatory
      monitoring vastly expand the scope of self-report and physiological measurement
      and will likely contribute to a refined assessment of anxiety disorders.

PMID- 11454437
TI  - Psychoneuroendocrinological contributions to the etiology of depression,
      posttraumatic stress disorder, and stress-related bodily disorders: the role of
      the hypothalamus-pituitary-adrenal axis.
AB  - Following the assumption that stressors play an important part in the etiology
      and maintenance of psychiatric disorders, it is necessary to evaluate parameters
      reflecting stress-related physiological reactions. Results from these
      examinations may help to deepen the insight into the etiology of psychiatric
      disorders and to elucidate diagnostic uncertainties. One of the best-known stress
      related endocrine reactions is the hormonal release of the hypothalamic-pituitary
      adrenal (HPA) axis. Dysregulations of this axis are associated with several
      psychiatric disorders. Profound hyperactivity of the HPA-axis has been found in
      melancholic depression, alcoholism, and eating disorders. In contrast,
      posttraumatic stress disorder, stress-related bodily disorders like idiopathic
      pain syndromes, and chronic fatigue syndrome seem to be associated with
      diminished HPA activity (lowered activity of the adrenal gland). Hypotheses
      referring to (a) the psychophysiological meaning and (b) the development of these
      alterations are discussed.

PMID- 11454438
TI  - Food deprivation and emotional reactions to food cues: implications for eating
      disorders.
AB  - Two studies examined emotional responding to food cues. In experiment 1, normal
      college students were assigned to 0-, 6- or 24-h of food deprivation prior to
      presentations of standard emotional and food-related pictures. Food deprivation
      had no impact on responses elicited by standard emotional pictures. However,
      subjective and psychophysiological reactions to food pictures were affected
      significantly by deprivation. Importantly, food-deprived subjects viewing food
      pictures showed an enhanced startle reflex and increased heart rate. Experiment 2
      replicated the food deprivation effects from experiment 1, and examined
      participants reporting either a habitual pattern of restrained (anorexia-like) or
      binge (bulimia-like) eating. Food-deprived and binge eater groups showed startle
      potentiation to food cues, and rated these stimuli as more pleasant, relative to
      restrained eaters and control subjects. The results are interpreted from the
      perspective that startle modulation reflects activation of defensive or
      appetitive motivation. Implications of the data for understanding eating
      disorders are considered.

PMID- 11454439
TI  - Psychophysiology of arterial baroreceptors and the etiology of hypertension.
AB  - Arterial baroreceptors are sensitive to blood pressure dependent blood vessel
      dilation. They play a key role in the short term regulation of blood pressure.
      Their impact on psychological and psychophysiological aspects is of increasing
      interest. The review focuses on experimental techniques for the controlled
      baroreceptor manipulation. Results from the application of these techniques show
      that baroreceptor activation influences the cardiovascular system as well as
      central nervous functioning: Behavioral and electrophysiological measures of
      arousal, low level reflexes and pain responses are modulated through baroreceptor
      manipulation. The observation of an overall dampening ('barbiturate like') effect
      of baroreceptor activity led Dworkin et al. formulate the theory of learned
      hypertension: Subjects might experience blood pressure dependent baroreceptor
      activation as stress and pain relieving. High blood pressure periods become
      negatively reinforced. Phasic high blood pressure might develop as a coping
      strategy. Data from a longitudinal human study supporting this theory are
      reported.

PMID- 11454440
TI  - Membrane permeability. Membranes and sorting. Web alert.
AB  - A selection of World Wide Web sites relevant to papers published in this issue of
      Current Opinion in Cell Biology.

PMID- 11454442
TI  - A genomic view of yeast membrane transporters.
AB  - The yeast membrane transporters play crucial roles in functions as diverse as
      nutrient uptake, drug resistance, salt tolerance, control of cell volume, efflux
      of undesirable metabolites and sensing of extracellular nutrients. A significant
      fraction of the many transporters inventoried after sequencing of the yeast
      genome has been characterised by classical experimental approaches. Post-genomic
      analysis has allowed a more extensive characterisation of transporter categories
      less tractable by genetics, for instance of transporters of intracellular
      membranes or transporters encoded by multigene families and displaying
      overlapping substrate specificities. A complete view of the role of membrane
      transporters in the metabolism of yeast may not be far off.

PMID- 11454443
TI  - Ion homeostasis during salt stress in plants.
AB  - Recent progress has been made in the characterization of cation transporters that
      maintain ion homeostasis during salt stress in plants. Sodium-proton antiporters
      at the vacuolar (NHX1) and plasma membrane (SOS1) have been identified in
      Arabidopsis. SOS1 is regulated by the calcium-activated protein kinase complex
      SOS2-SOS3. In yeast, a transcription repressor, Sko1, mediates regulation of the
      sodium-pump ENA1 gene by the Hog1 MAP kinase. The recent visualization at the
      atomic level of the inhibitory site of sodium in the known target Hal2 has helped
      identify the interactions determining Na(+) toxicity.

PMID- 11454444
TI  - Ion homeostasis and apoptosis.
AB  - Alterations in the transmembrane gradients of several physiological ions may
      influence programmed cell death. In particular, recent data suggest that
      increases in intracellular calcium may either promote or inhibit apoptosis,
      depending on the level, timing and location, whereas loss of intracellular
      potassium promotes apoptosis.

PMID- 11454445
TI  - Protein export and drug efflux through bacterial channel-tunnels.
AB  - The bacterial protein TolC assembles into an alpha-helical trans-periplasmic
      tunnel, which is embedded in the outer membrane by a contiguous beta-barrel
      channel. TolC and its homologues thus provide large exit ducts for a wide range
      of substrates, including protein toxins and antibacterial drugs, that are engaged
      by specific recognition proteins in the cytosolic membrane.

PMID- 11454446
TI  - The essence of excitation.
AB  - The amino acid glutamate is the major excitatory neurotransmitter in a range of
      organisms from Caenorhabditis elegans to mammals, and it mediates the information
      processing that underlies essentially all behavior. Recent advances in our
      understanding of glutamate storage and release now illuminate how this ubiquitous
      amino acid can function as a signalling molecule.

PMID- 11454447
TI  - Lipid and mechano-gated 2P domain K(+) channels.
AB  - The two pore domain K(+) channels TREK and TRAAK are opened by membrane stretch.
      The activating mechanical force comes from the bilayer membrane and is
      independent of the cytoskeleton. Emerging work shows that mechano-gated TREK and
      TRAAK are opened by various lipids, including long chain polyunsaturated anionic
      fatty acids and neutral cone-shaped lysophospholipids. TREK-1 shares the
      properties of the Aplysia neuronal S channel, a presynaptic background K(+)
      channel involved in behavioral sensitization, a simple form of learning.

PMID- 11454449
TI  - ER quality control: towards an understanding at the molecular level.
AB  - The process of 'quality control' in the endoplasmic reticulum (ER) involves a
      variety of mechanisms that collectively ensure that only correctly folded,
      assembled and modified proteins are transported along the secretory pathway. In
      contrast, non-native proteins are retained and eventually targeted for
      degradation. Recent work provides the first structural insights into the process
      of glycoprotein folding in the ER involving the lectin chaperones calnexin and
      calreticulin. Underlying principles governing the choice of chaperone system
      engaged by different proteins have also been discovered.

PMID- 11454450
TI  - ER export: public transportation by the COPII coach.
AB  - The COPII coat produces ER-derived transport vesicles. Recent findings suggest
      that the COPII coat is a highly dynamic polymer and that efficient capture of
      cargo molecules into COPII vesicles depends on several parameters, including
      export signals, membrane environment, metabolic control and the presence of a
      repertoire of COPII subunit homologues.

PMID- 11454451
TI  - Adaptor-related proteins.
AB  - Two new adaptor-related protein complexes, AP-3 and AP-4, have recently been
      identified, and both have been implicated in protein sorting at the trans-Golgi
      network (TGN) and/or endosomes. In addition, two families of monomeric proteins
      with adaptor-related domains, the GGAs and the stoned B family, have also been
      identified and shown to act at the TGN and plasma membrane, respectively.
      Together with the two conventional adaptors, AP-1 and AP-2, these proteins may
      act to direct different types of cargo proteins to different post-Golgi membrane
      compartments.

PMID- 11454452
TI  - Dynamin family of mechanoenzymes.
AB  - The dynamin family of proteins is continually growing, and in recent years
      members have been localized to areas of mitochondrial fission, plant
      phragmoplasts and chloroplasts, and viral ribonucleoprotein complexes. All the
      dynamin-like proteins examined to-date appear to assemble into oligomers, such as
      rings or spirals; however, it remains to be determined if a global mechanism of
      action exists. Even the role of dynamin in vesicle formation remains
      controversial as to whether it behaves as a molecular switch or as a
      mechanochemical enzyme.

PMID- 11454453
TI  - Endocytotic mechanisms in synapses.
AB  - Nerve terminals are highly enriched in proteins needed for endocytosis. Although
      constitutive and ligand-stimulated endocytosis take place in nerve terminals, the
      primary type is compensatory endocytosis--the process by which a cell retrieves
      the additional membrane added to cell surface by a regulated secretory event.
      This process has been extensively characterized using electrophysiological
      techniques. Except for an unusual form of coupled exo- and endocytosis called
      kiss-and-run release, compensatory endocytosis appears to use basically the same
      clathrin-mediated mechanisms as the constitutive and ligand stimulated type. The
      remarkable speed and selectivity of compensatory endocytosis may be achieved by
      concentrating the machinery at specialized sites in the nerve terminal adjacent
      to exocytosis sites and by the use of neuronal isoforms of the proteins that
      mediate endocytosis.

PMID- 11454454
TI  - Roles of lipid rafts in membrane transport.
AB  - Cholesterol-sphingolipid microdomains (lipid rafts) are part of the machinery
      ensuring correct intracellular trafficking of proteins and lipids. The most
      apparent roles of rafts are in sorting and vesicle formation, although their
      roles in vesicle movement and cytoskeletal connections as well as in vesicle
      docking and fusion are coming into focus. New evidence suggests that
      compositionally distinct lipid microdomains are assembled and may coexist within
      a given membrane. Important clues have also been uncovered about the mechanisms
      coupling raft-dependent signaling and endocytic uptake.

PMID- 11454455
TI  - Implications of lipid microdomains for membrane curvature, budding and fission.
AB  - Recent studies have highlighted the importance of monolayer and bilayer curvature
      for the budding and fission of biological membranes. Other lines of research,
      addressing the structure of planar biological membranes, have revealed the
      existence of cholesterol-based membrane microdomains. Here, we comment on the
      significance of microdomains for curved membranes, with special emphasis on
      budding and fission.

PMID- 11454456
TI  - The role of phosphoinositides in membrane transport.
AB  - Phosphoinositides serve as intrinsic membrane signals that regulate intracellular
      membrane trafficking. Recently, phosphoinositides have been found to direct the
      localization and activity of effector proteins containing consensus sequence
      motifs such as FYVE, PH and ENTH domains. In addition, recent results show that
      regulated synthesis and turnover of phosphoinositides by membrane-associated
      phosphoinoside kinases and phosphatases spatially restrict the location of
      effectors critical for cellular transport processes, such as clathrin-mediated
      endocytosis, autophagy, phagocytosis, macropinocytosis and biosynthetic
      trafficking.

PMID- 11454457
TI  - PI(4,5)P(2) regulation of surface membrane traffic.
AB  - Phosphatidylinositol 4,5-biphosphate (PI[4,5]P(2)) has emerged as an important
      signaling molecule in the membrane for regulating vesicle exo- and endocytosis
      and the accompanying actin cytoskeletal rearrangements. Localization studies with
      GFP-tagged binding domains and antibodies provide new views of the non-uniform,
      dynamic distribution of PI(4,5)P(2) in membranes and its organization in raft
      like domains. The targeting of phosphoinositide kinases by GTPases can coordinate
      the reactions of membrane fusion and fission with cytoskeletal assembly,
      providing a basis for membrane movement.

PMID- 11454458
TI  - Ypt and Rab GTPases: insight into functions through novel interactions.
AB  - Ypt/Rab GTPases are key regulators of vesicular transport in eukaryotic cells.
      During the past two years, a number of new Ypt/Rab-interacting proteins have been
      identified and shown to serve as either upstream regulators or downstream
      effectors. Proteins that interact with these regulators and effectors of Ypt/Rabs
      have also been identified, and together they provide new insights into Ypt/Rab
      mechanisms of action. The picture that emerges from these studies suggests that
      Ypt/Rabs function in multiple and diverse aspects of vesicular transport. In
      addition, not only are Ypt/Rabs highly conserved, but their functions and
      interactions are as well. Interestingly, crosstalk among Ypt/Rabs and between
      Ypt/Rabs and other signaling factors, suggest the possibility of coordination of
      the individual vesicular transport steps and of the protein transport machinery
      with other cellular processes.

PMID- 11454459
TI  - Antimalarial halorosellinic acid from the marine fungus Halorosellinia oceanica.
AB  - Three known compounds, 2-hexylidene-3-methylsuccinic acid (1), cytochalasin Q
      (2), and 5-carboxymellein (3), together with two new derivatives, 2-hexylidene-3
      methylsuccinic acid 4-methyl ester (4) and an ophiobolane sesterterpene named
      halorosellinic acid (5), were isolated from culture broth of the marine fungus
      Halorosellinia oceanica BCC 5149. Compounds 1-3 exhibited moderate cytotoxicity
      against KB and BC-1 cell lines with IC(50) values of 1-13 microg/mL, while
      compounds 2, 3, 5, and 6 showed antimalarial activity with respective IC(50)
      values of 17, 4, 13, and 19 microg/mL. Halorosellinic acid (5) possessed only
      weak antimycobacterial activity with the minimum inhibitory concentration of 200
      microg/mL.

PMID- 11454460
TI  - Benzyloxybenzaldehyde analogues as novel adenylyl cyclase activators.
AB  - Several benzyloxybenzaldehyde analogues were prepared and found to have
      significant inhibitory activity toward neutrophil superoxide formation.
      Consequently, these compounds were evaluated for cAMP-elevating capability. Among
      them, benzyloxybenzaldehyde (7), exhibiting activity equivalent to forskolin, was
      determined as an adenylyl cyclase activator since it elevates cAMP levels by
      activation of adenylyl cyclase but not by inhibition of phosphodiesterase. Having
      a chemical structure very different from known adenylyl cyclase activators,
      compound 7 is recommended by us for use as a new lead compound in the future
      development of adenylyl cyclase activators.

PMID- 11454461
TI  - The development of new carboxylic acid-based MMP inhibitors derived from a
      cyclohexylglycine scaffold.
AB  - A series of carboxylic acids was prepared based on cyclohexylglycine scaffolds
      and tested for potency as matrix metalloproteinase (MMP) inhibitors. Detailed SAR
      for the series is reported for five enzymes within the MMP family, and a number
      of inhibitors such as compound 18 display low nanomolar potency for MMP-2 and MMP
      13, while selectively sparing MMP-1 and MMP-7.

PMID- 11454462
TI  - Microwave-assisted [6+4]-cycloaddition of fulvenes and alpha-pyrones to azulene
      indoles: facile syntheses of novel antineoplastic agents.
AB  - A microwave-enhanced [6+4]-cycloaddition reaction between 6-aminofulvene and
      pyrones followed by CO(2) extrusion provides azulene-indoles which display
      interesting antineoplastic activity.

PMID- 11454463
TI  - Synthesis and biological activities of novel structural analogues of 2
      arachidonoylglycerol, an endogenous cannabinoid receptor ligand.
AB  - Novel analogues of 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid
      receptor ligand, were developed. Chemical synthesis of these analogues (2-AGA105
      and 2-AGA109) was accomplished starting from 2-octyn-1-ol and diethyl malonate
      and employing Wittig coupling of triene phosphonate with an aldehyde intermediate
      in a convergent and stereoselective manner. These analogues should be useful lead
      compounds for the development of novel 2-AG mimetics.

PMID- 11454464
TI  - A short synthesis of argatroban. a potent selective thrombin inhibitor.
AB  - Argatroban was synthesized in seven steps from 4-methylpiperidine. The
      condensation of (+/-)-trans-benzyl 4-methylpipecolic acid ester with N(alpha)-Boc
      N(omega)-nitro-L-arginine led to two diastereomers that were separated. One of
      them is the precursor of argatroban.

PMID- 11454465
TI  - Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human
      cytomegalovirus replication.
AB  - The synthesis and antiviral evaluation of unsymmetrical indolocarbazole
      derivatives of Arcyriaflavin A, substituted with a range of alkyl groups at the
      indole nitrogen, is described. Structure-activity relationships in this series
      against human cytomegalovirus (HCMV) replication in cell culture are reported.
      Compound 4b was identified as potent inhibitor of HCMV (IC(50)=19 nM), which
      retained activity against a range of HCMV strains including ganciclovir resistant
      isolates.

PMID- 11454466
TI  - Anti-influenza virus activities of 2-alkoxyimino-n-(2-isoxazolin-3
      ylmethyl)acetamides.
AB  - A series of 2-alkoxyimino-N-(2-isoxazolin-3-ylmethyl)acetamides and related
      compounds were synthesized and their antiviral activities against human influenza
      A virus were assessed. Studies of the structure-activity relationships revealed
      the strongest antiviral activity when position-5 of the isoxazoline ring was
      substituted with a tert-butyl group. When the alkoxyimino moiety was substituted
      with a methyl, ethyl, isopropyl or allyl group, good antiviral activity was
      obtained. Among the geometrical isomers at the oxime moiety, the E-isomers were
      more active than the Z-isomers. Among the compounds examined, (E)-2-allyloxyimino
      2-cyano-N-(5-tert-butyl-2-isoxazolin-3-ylmethyl)acetamide (1j) was the most
      active inhibitor with an EC(50) of 3 microg/mL in vitro.

PMID- 11454467
TI  - Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin
      albumin conjugates.
AB  - Two doxorubicin albumin conjugates (A-DP1 and A-DP2), which differ in their
      substrate specificity for the matrix metalloproteinases MMP2 and MMP9, were
      prepared by binding maleimide doxorubicin peptide derivatives to the cysteine-34
      position of human serum albumin. The incorporated octapeptide, Gly-Pro-Gln-Arg
      Ile-Ala-Gly-Gln, in A-DP2 is not cleaved by activated MMP2 and MMP9 in contrast
      to Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln incorporated in A-DP1 that is cleaved
      efficiently by activated MMP2 and MMP9 liberating a doxorubicin tetrapeptide. A
      DP1 showed antiproliferative activity in a murine renal cell carcinoma line in
      the low micromolar range (IC(50) value approximately 0.2 microM).

PMID- 11454468
TI  - Discovery and SAR of org 24598-a selective glycine uptake inhibitor.
AB  - The discovery of Org 24598, one of the first potent and selective inhibitors of
      the glycine transporter is discussed. In vitro structure-activity relationships
      (SARs) data for interaction of a ligand with this system is discussed.

PMID- 11454469
TI  - alpha(v)beta(3) Antagonists based on a central thiophene scaffold.
AB  - A series of novel, highly potent alpha(v)beta(3) antagonists based on a thiophene
      scaffold and containing an acylguanidine as an Arg-mimetic is described. A number
      of structural features, such as cyclic versus open guanidine and a variety of
      lipophilic side chains, carbamates, sulfonamides and beta-amino acids were
      explored with respect to inhibition of alpha(v)beta(3) mediated cell adhesion and
      selectivity versus alpha(IIb)beta(3) binding. In addition, compound 19 was found
      to be active in the TPTX model of osteoporosis.

PMID- 11454470
TI  - Substituted 4-phenyl-2-(phenylcarboxamido)-1,3-thiazole derivatives as
      antagonists for the adenosine A(1) receptor.
AB  - The synthesis and receptor binding of novel adenosine receptor antagonists is
      described. We found that non-xanthine 4-phenyl-2-(phenylcarboxamido)-1,3-thiazole
      derivatives may have high affinity and substantial selectivity for the adenosine
      A(1) receptor.

PMID- 11454471
TI  - Substituent effects within the DNA binding subunit of CBI analogues of the
      duocarmycins and CC-1065.
AB  - A series of CBI analogues of the duocarmycins and CC-1065 exploring substituent
      effects within the first indole DNA binding subunit are detailed. Substitution at
      the indole C5 position led to cytotoxic potency enhancements that are > or =1000
      fold, providing simplified analogues containing a single DNA binding subunit that
      are more potent (IC(50)=2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065.

PMID- 11454472
TI  - Design and synthesis of a highly selective EP2-receptor agonist.
AB  - EP2-receptor selective agonist 3 was identified by the structural hybridization
      of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more
      stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv
      administration of which to anesthetized rats suppressed uterine motility, while
      PGE(2) 2a stimulated uterine motility.

PMID- 11454473
TI  - Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7
      dithiaPG derivatives with high selectivity.
AB  - A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as
      highly selective EP4-receptor agonists starting from the chemical modification of
      7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were
      maximized in 3 and 4.

PMID- 11454474
TI  - Design and synthesis of a highly selective EP4-receptor agonist. Part 2: 5-thia
      and 9beta-haloPG derivatives with improved stability.
AB  - Further chemical modification to identify more chemically stabilized EP4-receptor
      selective agonists was continued. As a result, a further two EP4-receptor
      selective agonists 5-thiaPGE(1) 2a, 10 and 9beta-chloroPGF(2) analogue 11 were
      discovered.

PMID- 11454475
TI  - Concise synthesis of ciguatoxin ABC-ring fragments and surface plasmon resonance
      study of the interaction of their BSA conjugates with monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs), 4H2 and 6H7, were prepared previously using a
      protein conjugate of a 1:1 epimeric mixture of the synthetic ABC-ring fragments
      of ciguatoxin (CTX), 3 and 4. Here, the interactions of these mAbs with the
      fragments of CTX and CTX3C, 3 and 5, were investigated by surface plasmon
      resonance (SPR) spectroscopy in an attempt to clarify an antigenic determinant.
      Compared with the previous synthesis, the fragment 3 possessing the 2S
      configuration was synthesized from tri-O-acetyl-D-glucal much more effectively.
      The mAb 4H2 was already known to show a dose-dependent binding to the bovine
      serum albumin (BSA) conjugate of 3, but not to that of 5. The present SPR study
      of 4H2 demonstrates that the A-ring side chain of 3 plays a decisive role as an
      epitope. Therefore, SPR can effectively replace the ELISA method for the analysis
      of mAbs.

PMID- 11454476
TI  - CoMFA of artemisinin derivatives: effect of location and size of lattice.
AB  - A CoMFA study of artemisinin derivatives with changes of the location and the
      number of lattice points was performed. The location of probe atoms in a large
      lattice has practically no effect on the cross-validated r(2) value (r(2)(cv)).
      The selection of only 18 probe atoms around the peroxide bond, considering the
      action mechanism of artemisinin, provided a less time-demanding and more reliable
      CoMFA model, which forecasts better than the large lattice model despite the
      lower r(2)(cv) value. Only 1 A displacement of the small lattice caused a
      reduction of cross-validated r(2) value of more than 50%, which indicates the
      lattice location played an important role in this small lattice model.

PMID- 11454477
TI  - A novel method for the preparation of amino-substituted hypocrellin B.
AB  - A series of amino-substituted hypocrellins derived from hypocrellin B (HB) were
      synthesized by a novel mild method, in which the peri-hydroxylated
      perylenequinone structure of hypocrellin was preserved by the reaction of HB with
      an amine. The red absorption of the resulting products was significantly enhanced
      relative to the parent hypocrellins, which will significantly improve its
      photodynamic therapy effectiveness.

PMID- 11454478
TI  - Synthesis and photodynamic action of diphenyl-2,3-dihydroxychlorin: a potential
      tumor photosensitizer.
AB  - The synthesis, photophysical properties of diphenyl-2,3-dihydroxychlorin (DPCOH)
      and its photocytotoxicity to tumor cells are described. DPCOH exhibits
      photodynamic activity in terms of type I and type II mechanisms under
      irradiation. The quantum yield of (1)O(2) in CHCl(3) is 0.7. For the
      photocytotoxicity to tumor cells, DPCOH proved to be 200 times more potent than
      HPD, and the dark toxicity is low (dark IC(90)>32 microg/mL).

PMID- 11454482
TI  - Patient focused management: cost versus value.

PMID- 11454483
TI  - Combination therapy for postoperative nausea and vomiting - a more effective
      prophylaxis?
AB  - The problem of postoperative nausea and vomiting (PONV) remains far from being
      resolved. Despite the introduction of new classes of antiemetics and a vast
      amount of published research, there is a general impression that there has been
      little progress in this area. The multifactorial etiology of PONV might be better
      addressed using a combination of drugs acting at different receptor sites. This
      approach of balanced antiemesis may be the answer towards achieving a significant
      improvement in the management of PONV. This article will cover the different
      strategies used to prevent PONV with particular emphasis on combination
      antiemetics. A review of the currently available methods to manage PONV as well
      as the physiological and pharmacological basis of combination therapy is
      presented.

PMID- 11454484
TI  - Hernia surgery for the third millennium. Does classical herniorraphy still play a
      role?
AB  - The steadily increasing use of prosthetic grafts in hernia repairs can be said to
      play down the classical approach for repairing groin hernia. We retrospectively
      report on 894 patients operated on for groin hernia at our out-patient surgery
      clinic from June 1992 to May 1998. Herniorraphy was widely performed (96.3%). The
      recurrence rate was of 1.6% (overall). For patients younger than 45 yr with no
      systemic concurrent disease, as few as 0.1% relapsed after a 58-month average
      follow-up. According to our results, ambulatory herniorraphy can provide an
      excellent degree of efficiency in selected young patients suffering from indirect
      unilateral primary groin hernia. Likewise, we regard the prosthetic repair as the
      gold standard technique in those patients with a weakened posterior inguinal
      wall.

PMID- 11454485
TI  - Two percent lidocaine spinal anaesthesia compared with sevoflurane anaesthesia in
      ambulatory knee surgery - cost-effectiveness, home readiness and recovery
      profiles.
AB  - A total of 60 patients scheduled for elective knee arthroscopy were randomized to
      receive spinal anaesthesia (SA) with 2% lidocaine (n=30) or general anaesthesia
      with sevoflurane (SE) (n=30). SA and SE were compared in terms of the total costs
      of anaesthesia. The time to reach home readiness and the total time spent in the
      recovery unit (RU) were assessed. The early postoperative period and recovery at
      24 h and 1 week were evaluated in terms of the incidence of pain, sedation,
      nausea and general satisfaction with the method of anaesthesia and postoperative
      instructions. The total costs of anaesthetic materials in the operation theatre
      (OT) and anaesthetic materials and personnel costs until home readiness was
      achieved in the RU were 160.7 FIM (1 FIM=0.17 EUR) for SA and 171.0 FIM for SE
      (not significant). The corresponding sums were 197.2 FIM for SA and 224.4 FIM for
      SE (P=0.001) when the total stay in RU was considered. The time to reach home
      readiness was 140.8 min (S.D. 52) in the SA group and 96.4 min (S.D. 62) in the
      SE group (P=0.02). There were no differences in the total RU time (224.0 min
      (S.D. 67) for SA and 218.0 min (S.D. 59) for SE). The level of postoperative pain
      was generally low, as all the SA patients and 86.7% of the SE patients had VAS<4
      2 h postoperatively. Six SA patients (20.0%) had postoperative headache and two
      of them also had headache in the supine position. There were no headaches in the
      SE group (P=0.024). None of the patients in the SA group and six SE patients
      (20.0%) had nausea (needed treatment) in the RU (P=0.024). Four patients (13.3%)
      in the SE group and 1 patient (3.3%) in the SA group had nausea during the first
      24 h postoperatively. All the patients were alert 60 min postoperatively with no
      difference between the groups and they were very satisfied during the first 24 h.
      All patients would have liked to have a similar operation done on an ambulatory
      basis. 93.3% said they would choose the same kind of anaesthesia. 91.7% were
      satisfied with the first week.General anaesthesia with SE is more cost-effective
      than SA with 2% lidocaine in ambulatory knee surgery if a short RU time is
      needed. The patients do generally well, but the incidence of postspinal headache
      with SA, adequate postoperative pain treatment and the possibility to have nausea
      with SE must be kept in mind.

PMID- 11454486
TI  - Outpatient laparoscopic cholecystectomy. A prospective study with 100 consecutive
      patients.
AB  - One hundred patients with cholelithiasis were included in a prospective
      consecutive follow-up study to evaluate laparoscopic cholecystectomy in a day
      surgical setting. The median operating time was 70 min. In 96% of the patients,
      it was possible to perform peroperative cholangiography. The median time off work
      was 7 days and the median time to full recovery was 14 days. Five patients were
      admitted due to weakness/nausea. Six patients were admitted due to conversion to
      open surgery or choledocholithiasis. Eighty-nine patients were treated in
      ambulatory surgery. We conclude that laparoscopic outpatient cholecystectomy can
      be performed safely with a low unplanned admission rate.

PMID- 11454487
TI  - Anaesthetic drug costs in a district general hospital day surgery unit.
AB  - Propofol infusions for the induction and maintenance of anaesthesia are
      associated with many advantages. In some units their cost is thought to be
      prohibitive and limits their use. We have analysed the drug costs within a Day
      Surgery Unit over a 4-year period in order to quantify the cost of the increased
      use of these infusions. In our unit this has not resulted in increased
      anaesthetic drug costs. We therefore advocate the continued use and development
      of these techniques which have been shown to have many advantages both to
      patients and to the smooth and efficient running of theatre units.

PMID- 11454488
TI  - Is pain prophylaxis in minor gynaecological surgery of clinical value? a double
      blind placebo controlled study of paracetamol 1 g versus lornoxicam 8 mg given
      orally.
AB  - Methods: In a prospective randomised placebo controlled double-blind study 210
      ASA I-II women scheduled for elective termination of pregnancy received 1 g
      paracetamol, 8 mg lornoxicam or placebo orally 60 min before anaesthesia which
      was standardised with propofol, fentanyl and oxygen in nitrous oxide 1:2.
      Postoperative pain was assessed by VAS-score at 30 and 60 min after end of
      surgery and at discharge as primary endpoints. Need for rescue medication and
      time to discharge were secondary endpoints. Results: All patients had an
      uncomplicated course. Overall pain intensity was low, however, the patients
      pretreated with lornoxicam had significantly less pain after surgery, no
      difference could however, be seen in need for rescue medication or time to
      discharge between the three groups. Conclusion: General pain prophylaxis may be
      argued in minor gynaecological surgical procedures where postoperative pain is of
      low intensity. If general prophylaxis is to be given in minor gynaecological
      surgery, a non steroidal anti-inflammatory (NSAID) such as lornoxicam, seems more
      efficacious as compared to a standard dose of 1 g paracetamol.

PMID- 11454489
TI  - The effects of lowering fresh gas flow during sevoflurane anaesthesia: a clinical
      study in patients having elective knee arthroscopy.
AB  - The potential for minimising anaesthetic gas consumption with a circle absorber
      system is related to fresh gas flow. This study measured the actual sevoflurane
      consumption during elective arthroscopy of the knee in 75 ASA I-II patients
      randomised to three fresh gas flow rates (6, 3, and 1.5 l/min) using sevoflurane
      and O(2):N(2)O (1:2) after intravenous induction with fentanyl and propofol. A
      circle absorber system was used with a laryngeal mask airway. Anaesthetic
      duration, discharge time and postoperative pain did not differ between groups.
      Sevoflurane consumption was more than doubled with each doubling of fresh gas
      flow (0.07+/-0.03; 0.16+/-0.05; 0.41+/-0.12 ml sevoflurane/min; for gas flow 1.5,
      3, 6 l/min; P<0.01). The hourly sevoflurane related cost decreased from 15.5 to
      2.8 US$ when reducing the fresh gas flow from 6 to 1.5 l/min. Decreasing the
      fresh gas flow from 6 to 1.5 l/min provides good anaesthetic depth with effective
      reduction in anaesthetic consumption, cost and environmental burden.

PMID- 11454490
TI  - Introduction of a hand trauma day surgery operating list.
AB  - Due to a huge increase in hand trauma referrals to our busy plastic surgical
      unit, we introduced a dedicated half-day hand trauma day surgery (HTDS) list to
      try and reduce the pressure on inpatient beds and length of wait for surgery. We
      reviewed the first 101 cases treated on the HTDS list to determine whether this
      allowed adequate specialist treatment of these injuries and to assess outcome and
      complications rates. Only one patient needed admission following surgery and our
      complication rate compared favourably with that of patients admitted and treated
      in the standard manner. We conclude that a HTDS list is both an effective and
      efficient method of treating a wide range of hand injuries.

PMID- 11454491
TI  - Pre-registration student nurses' perceptions of the day surgery unit.
AB  - An increasing number of complex surgical interventions are now taking place on a
      day case basis with some surgical specialities able to perform 80% of their
      elective surgery as day surgery. It is important that student nurses are exposed
      to clinical practice within the day surgery unit. Some students, for a variety of
      reasons, exhibit a reluctance to experience a day-surgery placement. The writer
      describes a programme of study which takes place before the students take up
      their placements to demonstrate that day surgery offers many opportunities for
      the delivery of highly skilled, specialised nursing care. Day Surgery Nursing is
      emerging as a speciality in its own right. The clinical skills of the nurse are
      required alongside the interpersonal, informational and psychological care-giving
      skills to ensure safety and comfort for the patient whilst in the unit and
      transfer home where responsibility for care, normally performed by nurses, now
      lies with the patients and their carers.

PMID- 11454492
TI  - Wound infection in day-surgery.
AB  - To determine the surgical wound infection rate associated with day-surgery and to
      assess whether infection was related to patient factors, a prospective study of
      all electively operated adult day-cases was carried out during a 6 month period
      between January and June 1996. The study included gastroenterological
      orthopaedic, vascular, plastic and urological surgery. No operations involving
      obviously infected patients were performed in the unit. Strict criteria for
      diagnosis of infection were used. All patients were examined on the 7th and 30th
      post-operative day. A total of 642 (98.8%) patients were included (316 females
      334 males). Infection developed in 22 of the 642 patients (3.5%), only three were
      diagnosed before the 7th day visit. Orthopaedic procedures accounted for more
      than 40% of the surgery, but only 22.7% of the wound infections. Gastroenterology
      made up nearly 36% of the procedures and accounted for 36.4% of the infections.
      Vascular procedures were 5.7% of the total but accounted for 18% of the
      infections. No correlation was found between age, gender, operation time or ASA
      group and the infection rate. The study is to small to quantify with statistical
      significance risk-factors associated with wound infection in ambulatory surgery.
      Our data may suggest that the type of surgery as well as individual factors
      associated with surgeons may influence the wound infection rate.

PMID- 11454494
TI  - Patterns and risk factors of change in somatic and mood symptoms among older
      adults.
AB  - PURPOSE: This paper was concerned with patterns of individual-level, longitudinal
      change in depressive symptoms and factors related to those patterns among
      Americans 70+ years of age. Two types of depressive symptoms were considered,
      somatic and mood symptoms. The paper focused on whether the patterns of change
      and the risk factors for these two types of symptoms differed, as we might expect
      among old and oldest-old adults. METHODS: The analytic sample included self
      respondents of the 1993--1995 Asset and Health Dynamics among the Oldest Old
      (AHEAD) study who were born in 1923 or earlier. Depressive symptoms were assessed
      using an abbreviated Center for Epidemiologic Studies-Depression (CES-D) Scale.
      The analyses involved examination of respondents' change scores in depressive
      symptoms and multivariate models using ordinary least squares (OLS) and seemingly
      unrelated regressions (SUR). RESULTS: In aggregate, somatic symptoms were more
      common than mood symptoms initially and over time. Despite differences in
      aggregate rates, AHEAD respondents' individual-level patterns of change for the
      two types of symptoms were similar; i.e., stability was the principal trend (53-
      60%), followed by improvement (21--26%). A number of factors related to change in
      one aspect of depressive symptoms and not the other, or had greater effects on
      one aspect of depressive symptoms than the other; e.g., physical health had
      greater effects on somatic than mood symptoms. CONCLUSIONS: This study suggests
      that, in investigations of the course and risk factors for depressive symptoms
      among people 70+ years of age, it is important to separate somatic symptoms from
      mood symptoms; their etiology may differ. In general, factors reflecting
      respondents' social milieu (e.g., bereavement, residential relocation) may have
      greater effects on mood than somatic symptoms, whereas certain factors
      representing physical health may have greater effects on somatic symptoms.

PMID- 11454495
TI  - Using a neural network to screen a population for asthma.
AB  - PURPOSE: To use a neural network to rank a population according to individual
      likelihood of asthma based on their responses to a respiratory questionnaire.
      METHODS: A final diagnosis of asthma can be made only after full clinical
      assessment but limited resources make it impossible to offer this to complete
      populations as part of a screening programme. Prioritisation is required so that
      review can be offered most promptly to those most in need. A stratified random
      sample of 180 from 6825 respondents to a community survey underwent clinical
      review. They were categorised according to likelihood of asthma by three
      independent experts whose opinions were combined into a single probability label
      for each patient. A neural network was trained to relate questionnaire responses
      to probability labels. The trained network was applied to the whole community to
      produce a ranking order based on likelihood of asthma. A screening threshold
      could then be set to correspond to available resources, and patients above this
      level with no recorded evidence of asthma diagnosis could be assessed clinically.
      Using the known probability labels from the training set, it was possible to
      derive the expected proportion of true asthmatics in any set of patients.
      RESULTS: If the screening threshold had been set to capture the top 10% of the
      ranked population (n = 683), then 239 patients above this threshold had no
      evidence of diagnosis and would need assessment. Of these, it would be expected
      that 74% would have the diagnosis confirmed. CONCLUSIONS: This approach allows
      prioritisation of a population where resources for diagnostic examination are
      limited.

PMID- 11454496
TI  - Path analysis and multi-criteria decision making: an approach for multivariate
      model selection and analysis in health.
AB  - PURPOSE: This paper introduces an approach that includes non-quantitative factors
      for the selection and assessment of multivariate complex models in health.
      METHODS: A goodness-of-fit based methodology combined with fuzzy multi-criteria
      decision-making approach is proposed for model selection. Models were obtained
      using the Path Analysis (PA) methodology in order to explain the
      interrelationship between health determinants and the post-neonatal component of
      infant mortality in 59 municipalities of Brazil in the year 1991. Socioeconomic
      and demographic factors were used as exogenous variables, and environmental,
      health service and agglomeration as endogenous variables. Five PA models were
      developed and accepted by statistical criteria of goodness-of fit. These models
      were then submitted to a group of experts, seeking to characterize their
      preferences, according to predefined criteria that tried to evaluate model
      relevance and plausibility. Fuzzy set techniques were used to rank the
      alternative models according to the number of times a model was superior to
      ("dominated") the others. RESULTS: The best-ranked model explained above 90% of
      the endogenous variables variation, and showed the favorable influences of income
      and education levels on post-neonatal mortality. It also showed the unfavorable
      effect on mortality of fast population growth, through precarious dwelling
      conditions and decreased access to sanitation. CONCLUSIONS: It was possible to
      aggregate expert opinions in model evaluation. The proposed procedure for model
      selection allowed the inclusion of subjective information in a clear and
      systematic manner.

PMID- 11454497
TI  - Driver's license and voter registration lists as population-based sampling frames
      for rural African Americans.
AB  - PURPOSE: To compare coverage of a state driver's license list and county voter
      registration lists as frames for sampling rural African Americans. METHODS: Name,
      birth date, sex, and county were extracted from records for all 18--59 year-old
      African Americans residing in eight rural North Carolina counties and listed in
      the North Carolina Driver license file [obtained as a SAS dataset from the
      University of North Carolina (UNC) Highway Safety Research Center] and in machine
      readable text files of registered voters (obtained from county boards of
      elections). Files were edited, merged, and matched by last name and date of birth
      to produce three files for each five-year age group, sex, and county: 1) persons
      listed only in the driver's file; 2) persons listed only in the voter's file; and
      3) persons listed in both. RESULTS: The median percentages of unique persons
      found only on the driver's list, only on the voter's list, and on both lists were
      54%, 17%, and 30% men, and 35%, 25%, and 41% women, respectively. CONCLUSIONS:
      The driver's list provided better coverage than did voter registration lists.
      Federal legislation that prohibits states from releasing driver's license lists
      for use in surveys removes a valuable resource for population-based research.

PMID- 11454498
TI  - Illicit drug use in one's social network and in one's neighborhood predicts
      individual heroin and cocaine use.
AB  - PURPOSE: The nature of competing social environmental factors' influence on
      substance abuse is unclear. A longitudinal study was undertaken to determine the
      relative power of social network and neighborhood characteristics to predict
      continuing illicit drug use. METHODS: Three hundred forty-two inner-city adults
      with a history of injection drug use were followed for 1 year; their heroin and
      cocaine use were assessed semiannually. Multiple logistic regression models were
      fit to determine the degree to which social network and neighborhood
      characteristics, assessed at baseline, predicted continuing heroin and/or cocaine
      use throughout the study period. RESULTS: Two hundred thirty-six (69%)
      participants reported continuing heroin and/or cocaine use. Drug use by members
      of the social network was a stronger predictor of participants' continuing drug
      use (OR = 4.31, 95% CI 2.51 to 7.40) than was a high level of drug-related
      arrests in the participant's neighborhood (OR = 2.41, 95% CI 1.24 to 4.71), after
      adjusting for drug treatment and demographic variables. Both seemed to have
      independent effects on study participants' drug use. CONCLUSIONS: These findings
      reiterate the importance of breaking ties with drug-using associates, even for
      those who reside in high-risk environments. Further work is needed to develop
      interventions that increase drug users' success in altering social network
      composition or also treat drug-using network members.

PMID- 11454499
TI  - Area characteristics and individual-level socioeconomic position indicators in
      three population-based epidemiologic studies.
AB  - PURPOSE: There is growing interest in incorporating area indicators into
      epidemiologic analyses. Using data from the 1990 U.S. Census linked to individual
      level data from three epidemiologic studies, we investigated how different area
      indicators are interrelated, how measures for different sized areas compare, and
      the relation between area and individual-level social position indicators.
      METHODS: The interrelations between 13 area indicators of wealth/income,
      education, occupation, and other socioenvironmental characteristics were
      investigated using correlation coefficients and factor analyses. The extent to
      which block-group measures provide information distinct from census tract
      measures was investigated using intraclass correlation coefficients. Loglinear
      models were used to investigate associations between area and individual-level
      indicators. RESULTS: Correlations between area measures were generally in the 0.5
      -0.8 range. In factor analyses, six indicators of income/wealth, education, and
      occupation loaded on one factor in most geographic sites. Correlations between
      block-group and census tract measures were high (correlation coefficients 0.85-
      0.96). Most of the variability in block-group indicators was between census
      tracts (intraclass correlation coefficients 0.72--0.92). Although individual
      level and area indicators were associated, there was evidence of important
      heterogeneity in area of residence within individual-level income or education
      categories. The strength of the association between individual and area measures
      was similar in the three studies and in whites and blacks, but blacks were much
      more likely to live in more disadvantaged areas than whites. CONCLUSIONS: Area
      measures of wealth/income, education, and occupation are moderately to highly
      correlated. Differences between using census tract or block-group measures in
      contextual investigations are likely to be relatively small. Area and individual
      level indicators are far from perfectly correlated and provide complementary
      information on living circumstances. Differences in the residential environments
      of blacks and whites may need to be taken into account in interpreting race
      differences in epidemiologic studies.

PMID- 11454500
TI  - Comparing biological measurements of vitamin C, folate, alpha-tocopherol and
      carotene with 24-hour dietary recall information in nonhispanic blacks and
      whites.
AB  - PURPOSE: To assess intake of several vitamins in preparation for a large cohort
      study investigating the effect of diet on risk of colon and prostate cancer.
      METHODS: The dietary intake of several vitamins were assessed using eight
      different 24-hour recalls and a 200-item food frequency questionnaire (FFQ) from
      each subject. Participants also attended a clinic where blood was drawn and body
      composition, weight, height, and blood pressure were measured. A total of 97
      black and 96 nonhispanic white subjects participated. The levels of alpha
      tocopherol, carotene, folate, and vitamin C in the blood were correlated with the
      dietary intakes as measured by both 24-hour recalls and FFQ. RESULTS:
      Correlations between blood levels and energy-adjusted dietary intake assessed by
      24-hour recalls (with supplements) were as follows: carotene (adjusted for serum
      cholesterol): 0.47 and 0.55 in black and white subjects, respectively; alpha
      tocopherol (adjusted for serum cholesterol): 0.61 (blacks) and 0.50 (whites);
      vitamin C: 0.22 (blacks) and 0.17 (whites); folate: 0.54 (blacks) and 0.55
      (whites). Correlations between blood levels and FFQ indices were smaller in
      magnitude: 0.34 and 0.28 for carotene in black and white subjects, respectively,
      0.37 and 0.56 for alpha-tocopherol (adjusted for serum cholesterol), 0.20 and
      0.03 for vitamin C and 0.24 and 0.32 for folate. CONCLUSIONS: The correlations
      observed were generally of modest to moderate size and were similar to or larger
      than those reported by others. This is despite variations in absorption,
      metabolism, and excretion of the vitamins and suggests that both the 24-hour
      recalls and the FFQ contain valid information.

PMID- 11454501
TI  - The effect of social desirability trait on self-reported dietary measures among
      multi-ethnic female health center employees.
AB  - PURPOSE: To evaluate the effect of social desirability trait, the tendency to
      respond in a manner consistent with societal expectations, on self-reported
      fruit, vegetable, and macronutrient intake. METHODS: A 61-item food frequency
      questionnaire (FFQ), 7-item fruit and vegetable screener, and a single question
      on combined fruit and vegetable intake were completed by 132 female employees at
      five health centers in eastern Massachusetts. Intake of fruit and vegetables
      derived from all three methods and macronutrients from the FFQ were fit as
      dependent variables in multiple linear regression models (overall and by
      race/ethnicity and education); independent variables included 3-day mean intakes
      derived from 24-hour recalls (24HR) and score on the 33-point Marlowe-Crowne
      Social Desirability scale (the regression coefficient for which reflects its
      effect on estimates of dietary intake based on the comparison method relative to
      24HR). RESULTS: Results are based on the 93 women with complete data and FFQ
      derived caloric intake between 450 and 4500 kcal/day. In women with college
      education, FFQ-derived estimates of total caloric were associated with under
      reporting by social desirability trait (e.g., the regression coefficient for
      total caloric intake was -23.6 kcal/day/point in that group versus 36.1
      kcal/day/point in women with education less than college) (difference = 59.7
      kcal/day/point, 95% confidence interval (CI) = 13.2, 106.2). Except for the
      single question on which women with college education tended to under-report
      (difference =.103 servings/day/point, 95% CI = 0.003, 0.203), there was no
      association of social desirability trait with self-reported fruit and vegetable
      intake. CONCLUSIONS: The effect of social desirability trait on FFQ reports of
      macronutrient intake appeared to differ by education, but not by ethnicity or
      race. The results of this study may have important implications for epidemiologic
      studies of diet and health in women.

PMID- 11454502
TI  - Retrospective vs. prospective coital frequency and menstrual cycle length in a
      contraceptive effectiveness trial.
AB  - PURPOSE: To determine how well information at enrollment would predict coital
      frequency and menstrual segment length during a prospective contraceptive
      effectiveness trial. METHODS: We compared retrospective reports of monthly coital
      frequency and menstrual segment (cycle) length with prospective information for
      women participating in a contraceptive trial of the Reality((R)) female condom.
      RESULTS: Participants reported slightly higher mean monthly coital frequency and
      slightly longer menstrual segments prior to the study than during the study (12.6
      acts vs. 12.0 acts per month and 30.8 days vs. 28.4 days). We examined the actual
      distribution of differences between the retrospective and prospective measures
      and found considerable variability. Among the 195 participants studied, parous
      women were less likely to predict accurately menstrual segment length (OR 0.4;
      95% CI 0.3--0.9), while older women were more likely to predict accurately coital
      frequency (OR 1.9; 95% CI 0.9--3.3). CONCLUSIONS: Coital frequency and menstrual
      segment length vary considerably over time. Hence, prospective data collection is
      essential to accurately characterize these variations and to properly interpret
      results from contraceptive trials and other studies concerned with fecundability
      and hazards of reproduction.

PMID- 11454503
TI  - A case-control study of nonsyndromic oral clefts in Maryland.
AB  - PURPOSE: Isolated, nonsyndromic oral clefts cases (n = 171) and unaffected
      controls (n = 182) were used to identify both genetic and environmental risk
      factors. METHODS: Infants born in Maryland between 1992 to 1998 with an isolated,
      nonsyndromic oral cleft [cleft lip (CL), cleft lip and palate (CLP), or cleft
      palate (CP)] were recruited and exposure plus family history data were collected.
      Controls were unaffected infants. DNA was collected from all cases and their
      parents, plus controls. RESULTS: No statistically significant association was
      found between any of the following: maternal smoking, vitamin use, urinary tract
      infection, or recreational drug use in either univariate analysis or after
      adjusting for maternal age and education. More control mothers reported alcohol
      use during the critical time period of pregnancy (one month before conception
      through the first trimester) as compared to case mothers. There was a 10-fold
      increase in risk to siblings of cases as compared to siblings of controls.
      Markers at four candidate genes were examined: transforming growth factor alpha
      (TGF alpha), transforming growth factor beta 3 (TGF beta 3), MSX1, and BCL3. Only
      MSX1 showed significant differences in allele frequencies between CP cases and
      controls. MSX1 also showed significant evidence of linkage disequilibrium with a
      susceptibility gene controlling risk for CP. CONCLUSION: Most environmental risk
      factors examined here gave little evidence of association with risk to isolated,
      nonsyndromic oral clefts, although any alcohol consumption seemed protective.
      MSX1 showed evidence of linkage disequilibrium in both case-control and case
      parent trio analysis.

PMID- 11454504
TI  - Dehydroepiandrosterone replacement therapy.

PMID- 11454505
TI  - Imaging in thyroid-associated orbitopathy.

PMID- 11454506
TI  - B-cell autoepitopes on the acetylcholinesterase-homologous region of human
      thyroglobulin: association with Graves' disease and thyroid eye disease.
AB  - OBJECTIVE: Thyroglobulin (Tg) is a large autoantigen involved in autoimmune
      thyroid diseases. Tg epitopes have, so far, been identified within large
      peptides. In the present study, we used small synthetic peptides to finely map
      serological epitopes on the highly immunogenic C-terminal region of Tg. Homology
      of this region to acetylcholinesterase (AChE) has been implicated in the
      pathogenesis of thyroid eye disease (TED) through cross-reactive antibodies.
      METHODS: We tested total IgG purified from four pilot Graves' disease (GD) sera
      reactive with both Tg and AChE and from three healthy controls, for reactivity
      against overlapping 20mer peptides (pin synthesis) covering the sequence 2171
      2748 of human Tg. Antibody-reactive peptides were subsequently synthesized by a
      solid-phase technique for confirmation with a large number of sera: 99 GD, 32
      Hashimoto's thyroiditis (HT) and 45 healthy controls. RESULTS: Peptides TgP15,
      TgP26 and TgP41 (amino acids 2339-2358, 2471-2490 and 2651-2670 respectively)
      were found to be targets of autoantibodies on intact Tg, recognized by a
      statistically significant proportion of GD sera (22.2%, 35.4% and 30.3%
      respectively), compared with HT (0%, 15.6% and 6.3% respectively) and healthy
      controls (0%, 4.4% and 4.4% respectively). The majority of GD sera (56.6%) were
      positive for at least one of the three peptides. In GD, TgP26 reactivity was
      found to be associated with TED (48.6% with TED versus 25.5% without TED,
      P<0.05). CONCLUSION: Some epitopes on the C-terminal region of Tg are associated
      with GD. A subset of Tg-reactive autoantibodies, directed to this region, is
      associated with TED and may be involved in the development of the disease.

PMID- 11454507
TI  - Expression pattern of the pendrin and sodium/iodide symporter genes in human
      thyroid carcinoma cell lines and human thyroid tumors.
AB  - OBJECTIVE: In the present study we analyzed the pattern of pendrin (PDS) and
      sodium/iodide symporter (NIS) gene expression in some thyroid carcinoma cell
      lines and a series of thyroid tumoral tissues. METHODS: Total RNA was extracted
      from all cell lines and from 53 tissues, and gene expression was examined by RT
      PCR. Semiquantitative 'multiplex' RT-PCR was used to assess variations in PDS
      gene expression among various thyroid pathologies. Pendrin expression was
      determined in the thyroid cell lines by Western blot analysis. RESULTS: PDS mRNA
      was expressed in all the cells investigated; conversely, NIS mRNA was detectable
      only in the B-CPAP cells. Pendrin protein was expressed in B-CPAP and WRO cell
      lines, reduced in FRO and absent in ARO cells. PDS gene expression was not
      detected in 5 of 25 differentiated thyroid carcinomas (DTC) while NIS gene was
      not expressed in six carcinomas. A concordance expression of both PDS and NIS
      transcripts was found in 20 DTC. In contrast, 2 neoplastic thyroid tissues
      carrying undetectable PDS mRNA maintained NIS transcript, and 3 thyroid
      carcinomas negative for NIS mRNA retained the expression of PDS gene. A
      semiquantitative analysis showed that the mean PDS mRNA levels were significantly
      decreased in DTC tissues. CONCLUSIONS: Our data demonstrate that pendrin
      expression: (i) is present in the more differentiated thyroid carcinoma cell
      lines studied; (ii) is reduced or absent in DTC tissues; (iii) may not correlate
      with the NIS expression. These alterations may contribute to the loss of iodine
      concentration ability detected in thyroid tumors.

PMID- 11454508
TI  - Effects of preoperative octreotide treatment on different subtypes of 90 GH
      secreting pituitary adenomas and outcome in one surgical centre.
AB  - OBJECTIVE: To investigate the possible impact of pretreatment with octreotide on
      different subtypes of GH-secreting pituitary adenomas and on the outcome of
      transnasal surgery. METHODS: We reviewed a consecutive series of 90 acromegalic
      patients treated with octreotide alone before transnasal surgery. On the basis of
      magnetic resonance imaging, the tumours were classified into four groups: group
      A, microadenoma (n=7); group B, transnasally resectable macroadenoma (n=21);
      group C, invasive, potentially transnasally resectable macroadenoma (n=43); group
      D, non-resectable grossly invasive macroadenoma (n=19). All patients were treated
      for at least 3 months before surgery, with a mean daily dose of 221+/-31 microg
      octreotide. The mean follow-up was 51.7+/-1.4 months. The comparative group
      included 57 acromegalic patients who were not receiving octreotide treatment.
      RESULTS: After pretreatment with octreotide, tumour shrinkage was clearly
      observed in 28 of the 90 patients (31%). At surgery, the tumours after octreotide
      treatment were more often white or grey in colour (91% compared with 75%) and
      were observed to be slightly more often fluid or soft in texture (86% compared
      with 79%) than those in the comparative series. Endocrinological remission was
      achieved in all patients in group A, 95.2% in group B, and 81.4% in group C. In
      only 10 of the 14 patients with tumour shrinkage in group C, endocrinological
      remission was also achieved (71.4%). In the comparative series, endocrinological
      remission was achieved in 92.9% of group A, 87.5% of group B, and 73.9% of group
      C. CONCLUSIONS: Octreotide treatment slightly improved the already relatively
      high rate of endocrinological remission in invasive, potentially transnasally
      resectable macroadenomas. The rate of tumour shrinkage was found to decrease with
      extrasellar size. With the exception of tumour growth in approximately 7% of
      invasive adenomas and pituitary apoplexy in one patient, there was no
      disadvantage associated with the octreotide pretreatment.

PMID- 11454509
TI  - Skin morphological changes in growth hormone deficiency and acromegaly.
AB  - OBJECTIVE: To evaluate the histomorphology of skin and its appendages, especially
      eccrine sweat glands, in patients with GH disorders, because reduced sweating
      ability in patients with growth hormone deficiency (GHD) is associated with
      increased risk of hyperthermia under stressed conditions. DESIGN AND METHODS: A
      skin biopsy was obtained from 17 patients with GHD treated with GH, five patients
      with untreated GHD, 10 patients with active acromegaly and 13 healthy controls.
      RESULTS: The sweat secretion rate (SSR) was significantly decreased in both the
      untreated (median 41 mg/30 min, range 9-79 mg/30 min) and the GH-treated (median
      98 mg/30 min, range 28-147 mg/30 min) patients with GHD compared with that in
      controls (median 119 mg/30 min, range 90-189 mg/30 min; P=0.001 and 0.01
      respectively). Epidermal thickness was significantly decreased in both untreated
      (median 39 microm, range 28-55 microm) and GH-treated patients with GHD (median
      53 microm, range 37-100 microm), compared with that in controls (median 66
      microm, range 40-111 microm; P<0.02). A statistically non-significant tendency
      towards thinner epidermis (median 59 microm, range 33-83 microm) was recorded in
      acromegalic patients (P=0.08) compared with controls. There was no significant
      difference in the area of the sebaceous glands in the biopsies between the three
      groups and the controls. The area of eccrine sweat gland glomeruli was
      significantly decreased in the untreated patients with GHD (median 16407 microm2,
      range 12758-43976 microm2) compared with that in controls (median 29446 microm2,
      range 13511-128661 microm2; P=0.03), but there was no significant difference
      between the GH-treated patients with GHD and controls. CONCLUSIONS: We conclude
      that GH, either directly or via IGF-I, may have both a structural and a
      functional effect on human skin and its appendages, and that patients with GHD
      have histomorphological changes in skin compared with controls. Importantly,
      these changes are not fully reversed despite long-term and adequate GH treatment
      in patients with childhood onset GHD.

PMID- 11454510
TI  - Familial isolated primary hyperparathyroidism--a multiple endocrine neoplasia
      type 1 variant?
AB  - OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is defined as
      hereditary primary hyperparathyroidism without the association of other diseases
      or tumors. Linkage analyses suggest that different genotypes can lead to the same
      phenotype of primary hyperparathyroidism. Hereditary syndromes associated with
      primary hyperparathyroidism are multiple endocrine neoplasia type 1 and type 2
      (MEN 1 and MEN 2). In MEN 1, multiple parathyroid adenomas occur in more than 90%
      of the patients. Therefore, it has been suggested that FIHP could represent a
      variant or partial expression of MEN 1. DESIGN: We report on a large FIHP kindred
      with a MEN1 gene mutation. Nineteen family members (aged 10 to 87 years) were
      screened. Furthermore, statistical comparison by Fisher's exact tests of FIHP
      families with MEN1 gene mutations and MEN 1 families with two or more
      endocrinopathies was carried out to investigate genotype-phenotype correlations.
      METHODS: Mutational analysis of leucocyte DNA was carried out by direct
      sequencing of the complete coding region of the MEN1 gene. Screening of MEN 1
      manifestations was carried out by determination of serum calcium, phosphate,
      parathyroid hormone, prolactin, ACTH, cortisol, IGF-I, gastrin, glucose, insulin,
      glucagon, serum potassium, aldosterone, plasma renin and urinary
      hydroxyindoleacetic acid. RESULTS: We detected an in-frame deletion mutation in
      exon 8 of the MEN1 gene resulting in the deletion of one glutamine acid residue
      at position 363. It was found in eight individuals. Two of these family members
      (aged 42 and 60 years) were operated for primary hyperparathyroidism, and three
      (aged 13 to 40 years) showed mild hypercalcemia and parathyroid hormone levels
      within the upper normal range or slightly elevated, without any clinical
      symptoms. Two individuals (aged 12 and 19 years) were normocalcemic. One could
      not be tested. None of them had clinical evidence of other MEN 1 manifestations.
      Statistical comparison of the mutation types in families with FIHP and families
      with two or more MEN 1-associated endocrinopathies reported in other studies
      reveals a significant difference. In families with FIHP, missense/in-frame
      mutations have been found in 87.5% of cases whereas in families with tumors in
      various endocrine glands these mutation types occur much less frequently (21-34%,
      P<0.05). CONCLUSIONS: These studies indicate that FIHP can represent a partial
      MEN 1 variant and is often caused by missense/in-frame mutations.

PMID- 11454511
TI  - Telomerase is not activated in human hyperplastic and adenomatous parathyroid
      tissue.
AB  - BACKGROUND: Telomerase is a specific enzyme that appears to have a key role in
      cellular senescence and the progression of neoplastic tissue. High telomerase
      activity has been found in several cancers, but not in most normal and benign
      tissue. Little is known about the influence of telomerase on the abnormal growth
      associated with hyperparathyroidism. OBJECTIVE: To analyse telomerase activity in
      parathyroid tissue obtained from 29 patients undergoing surgery for primary
      hyperparathyroidism. DESIGN: Tissue for telomerase activity measurements was
      collected from six hyperplastic, 20 adenomatous and 22 normal parathyroid glands.
      METHODS: The highly sensitive PCR-based telomeric repeat amplification protocol,
      TRAP, combined with ELISA, was used to detect telomerase activity in tissue
      extracts containing 3.0 microg protein. RESULT: Telomerase was not activated in
      any of the analysed tissue by 3 microg protein. Reassay of 12 samples containing
      6.0 microg protein verified these negative TRAP results. CONCLUSION: Our findings
      indicate that telomerase is not a part of the mechanism promoting parathyroid
      proliferation and the underlying conditions remain to be determined.

PMID- 11454512
TI  - Salivary cortisol measurement in normal-weight, obese and anorexic women:
      comparison with plasma cortisol.
AB  - OBJECTIVE: To compare salivary, plasma and urinary free cortisol (UFC)
      measurements in patients with anorexia nervosa, in whom an overdrive of the
      hypothalamic-pituitary-adrenal (HPA) axis is well established but information on
      salivary cortisol is lacking, in viscerally obese patients in whom subtle
      abnormalities of cortisol secretion and metabolism are postulated, and in normal
      weight healthy women. PARTICIPANTS AND EXPERIMENTAL DESIGN: Measurement of
      salivary cortisol offers a convenient way to assess the concentrations of free,
      biologically active cortisol in plasma in different physiopathological settings.
      Forty-seven drug-free, newly diagnosed women with active restrictive anorexia
      nervosa, 30 restrictive anorexic women undergoing chronic psychopharmacological
      treatment, 47 women with mild-to-moderate visceral obesity, 103 women with severe
      central obesity and 63 normal-weight healthy women entered the study. Salivary
      and blood samples were collected at 0800 h, 1700 h and 2400 h, together with
      three consecutive 24-h urine specimens for UFC determination. In controls and
      patients with anorexia nervosa (n=83), salivary and plasma cortisol were also
      measured after a 1-mg overnight dexamethasone suppression test (DST). In patients
      with anorexia nervosa, mood was rated by the Hamilton scale for anxiety and
      depression. RESULTS: Untreated patients with anorexia nervosa showed increased
      plasma and salivary cortisol and UFC concentrations (all P<0.001 compared with
      controls), and decreased cortisol suppression after DST in plasma and saliva
      (P<0.0001 and P<0.005 respectively compared with controls). These alterations
      were less pronounced, although still statistically significant, in treated
      patients with anorexia nervosa. Salivary cortisol was highly correlated with
      paired plasma cortisol in the whole population and after splitting the
      participants by group (P<0.0001). However, for plasma cortisol values greater
      than 500 nmol/l (the corticosteroid-binding globulin saturation point), this
      parallelism was lost. Taking plasma cortisol as a reference, the level of
      agreement for post-dexamethasone salivary and plasma cortisol was 58.9% among
      suppressors and 77.8% among non-suppressors (chi2 test: P<0.01). Decreased 0800
      h/2400 h cortisol ratios were observed in plasma and saliva in drug-free patients
      with anorexia nervosa (P<0.005 and P<0.05 respectively compared with controls),
      and in saliva in severely obese patients (P<0.05 compared with controls).
      Depression and anxiety scores were unrelated to cortisol concentrations in any
      compartment. CONCLUSIONS: Salivary cortisol measurement is a valuable and
      convenient alternative to plasma cortisol measurement. It enables demonstration
      of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of
      the cortisol diurnal rhythm in women with visceral obesity. With the
      establishment of more specific and widely acceptable cut-off values for dynamic
      testing, measurement of salivary cortisol could largely replace plasma cortisol
      measurement.

PMID- 11454513
TI  - Role of diabetes in influencing leptin concentration in elderly overweight
      patients.
AB  - BACKGROUND: Leptin, the product of the ob gene, could have a significant role in
      the pathogenesis of obesity and non-insulin-dependent diabetes mellitus. However,
      it is still debated whether different degrees of glucose tolerance may affect
      plasma leptin concentrations in obese patients. OBJECTIVE: To investigate whether
      diabetes might influence leptin concentrations in obese patients. METHODS: We
      evaluated clinical parameters, anthropometric measures, and sex hormones, fasting
      plasma leptin, glucose and insulin concentrations in 100 elderly obese diabetic
      patients and 100 obese non-diabetic control individuals matched for age and sex.
      RESULTS: After adjustment for age and fat mass, plasma leptin concentrations did
      not differ between diabetic and non-diabetic obese individuals, in both men and
      women. In all patients leptin was significantly related to body mass index, fat
      mass and the homeostasis model insulin resistance index; moreover we observed a
      significant relationship with fasting plasma glucose and age in diabetic obese
      women, and with blood pressure values and testosterone concentrations in diabetic
      obese men. Multiple regression analysis revealed age and fasting plasma glucose
      to be the only independent determinants of fasting plasma leptin in diabetic
      obese women. CONCLUSIONS: These data suggest that leptin concentrations do not
      differ between obese diabetic and obese non-diabetic elderly patients. Among
      correlates of the metabolic syndrome, systolic pressure seems to be related to
      leptin only in men. In the postmenopausal or andropausal status, sex hormones are
      related to leptin concentrations only in diabetic men; in diabetic women,
      however, high glucose seems to be relevant in maintaining the same leptin
      concentrations as in non-diabetic women with similar degree of obesity.

PMID- 11454514
TI  - Vitamin D receptor gene polymorphisms are associated with obesity in type 2
      diabetic subjects with early age of onset.
AB  - OBJECTIVE: Allelic variations in the vitamin D receptor (VDR) gene were reported
      to modulate insulin secretion in response to glucose. VDR was investigated as a
      candidate gene for type 2 diabetes mellitus (T2DM). METHOD: Four single
      nucleotide polymorphisms (SNPs) in intron 8 (BsmI, Tru9I, ApaI) and exon 9 (TaqI)
      of the VDR gene were examined in 309 unrelated French subjects with T2DM and 143
      controls. RESULTS: The distribution of alleles and genotypes of the four SNPs was
      similar in patients and controls. However, in patients whose age at diagnosis of
      diabetes was < or =45 years, homozygous subjects for the T-allele of the TaqI SNP
      had a higher body mass index (BMI) (31.7+/-6.7 kg/m2, P=0.0058) and an increased
      prevalence of obesity (81%, P=0.005) with respect to heterozygous subjects
      (27.9+/-5.0 kg/m2; 46%) or homozygous subjects for the t-allele (27.7+/-5.0
      kg/m2; 52%). Similar results were observed for homozygous subjects for the b
      allele of the BsmI SNP. Logistic regression analysis demonstrated that TT
      homozygosity was independently associated with obesity in these subjects (odds
      ratio, 4.64; 95% confidence interval (CI), 1.64-14.76; P=0.0056). CONCLUSION: VDR
      is not a major gene for T2DM in French Caucasians. However, polymorphisms in the
      VDR gene are associated with the susceptibility to obesity in subjects with early
      onset T2DM. The pathophysiological mechanisms of these associations remain
      unexplained, but they could be related to a direct effect of vitamin D in
      adypocyte differentiation and metabolism, or to an indirect effect by modulation
      of insulin secretion.

PMID- 11454515
TI  - Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15
      hydroxyprostaglandin dehydrogenase mRNA expression during human gestation.
AB  - BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2
      (11beta-HSD2) plays an important role in protecting the fetus from high maternal
      glucocorticoid concentrations by converting cortisol to inactive cortisone.
      Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the
      prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH),
      because cortisol reduces the gene expression and enzyme activity of PGDH in human
      placental cells. OBJECTIVE: To examine developmental changes in placental 11beta
      HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human
      pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal
      pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta
      HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR.
      RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased
      significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In
      addition, there was a significant correlation between the two enzymes (r=0.58,
      P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta
      HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of
      11beta-HSD2 prevents increasing maternal cortisol concentrations from
      transplacental passage and is exerted at the gene level. 11beta-HSD2 up
      regulation may also lead to an increase in PGDH mRNA concentrations that, until
      term, possibly delays myometrial contractions induced by prostaglandins.

PMID- 11454516
TI  - Production of hyaluronan and chondroitin sulphate proteoglycans from human
      arterial smooth muscle--the effect of glucose, insulin, IGF-I or growth hormone.
AB  - BACKGROUND: Although it is recognized that the extracellular matrix is important
      for cell proliferation, migration and metabolism of growth factors, the
      regulation of the synthesis of hyaluronan and chondroitin sulphate proteoglycan
      (CSPG) in the vessel wall is poorly understood. OBJECTIVE: To examine the role of
      glucose, insulin, IGF-I and human growth hormone (hGH) on the accumulation of
      hyaluronan and CSPG using cultures of human aortic smooth muscle cells. METHODS:
      The cultures were exposed for 36 h. The CSPG content in the incubation medium was
      measured by a combination of digestion with testicular hyaluronidase and
      precipitation of [35SO4(2-)]-labelled material with ethanol and trichloroacetic
      acid. Hyaluronan was estimated using a radiometric assay. RESULTS: Glucose and
      insulin reduced the amount of synthesized hyaluronan (2P<0.01). Stimulation of
      synthesis was seen with hGH (2P<0.01), whereas no effect was observed with IGF-I.
      The production of CSPG was increased with glucose and hGH (2P<0.01), but showed
      no change with insulin. CONCLUSIONS: The present data obtained with human
      arterial smooth muscle cells in vitro showed that glucose, insulin and hGH can
      influence the accumulation of hyaluronan and CSPG. These observations may be
      relevant for an understanding of diabetic macroangiopathy.

PMID- 11454517
TI  - Serum parathyroid hormone, but not menopausal status, is associated with the
      expression of osteoprotegerin and RANKL mRNA in human bone samples.
AB  - OBJECTIVE: Osteoprotegerin (OPG) and its ligand 'receptor activator of NF-kB
      ligand' (RANKL) are important regulators of bone metabolism. RANKL, expressed in
      osteoblasts, activates osteoclast differentiation and osteoclast function by
      binding the 'receptor activator of NF-kB' (RANK), expressed in ostoclast
      precursors and mature osteoclasts. The effect is prevented by OPG, a soluble
      receptor of RANKL. In vitro studies have suggested that estrogen stimulates OPG,
      whereas parathyroid hormone (PTH) inhibits OPG expression and stimulates the
      expression of RANKL. DESIGN: In the present study, we examined the relationship
      between the menopause, serum PTH and the expression of OPG and RANKL in human
      bone tissue in vivo. METHODS: To address this question, we established a 5'
      nuclease assay to quantify the mRNA copies of human OPG and RANKL, normalized to
      the number of copies of beta-actin mRNA in 169 women (mean age: 52.4+/-11.6
      years), who underwent surgery for early breast cancer. Intact serum PTH was
      measured by chemoluminescence in 61 women. RESULTS: We found no significant
      difference in the expression of OPG and RANKL between postmenopausal women and
      premenopausal women. Also, the ratio of RANKL to OPG was unchanged in relation to
      the menopausal status. Serum PTH was negatively associated with the expression of
      OPG (r=-0.33, P=0.01), but also, surprisingly, with the expression of RANKL (r=
      0.28, P=0.03). CONCLUSION: We failed to observe the expected changes in the
      expression of OPG and RANKL in human bone samples at menopause. High in vivo
      levels of circulating PTH are accompanied by low levels of expression of the two
      transcripts in human bone tissue.

PMID- 11454518
TI  - Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.
AB  - OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for
      the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in
      adrenal tumorigenesis, as a means of investigating the molecular basis of
      sporadic adrenal tumors, which is unknown. DESIGN: Screening for the presence
      CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and
      its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal
      tumors. METHODS: Single-strand conformation polymorphism and sequencing were used
      for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In
      a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and
      immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed.
      RESULTS: No somatic mutations of CDKN1C were found in the tumors analyzed, in
      spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas.
      Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas,
      associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In
      the normal adrenal cortex, CDNC expression was strictly nuclear and confined to
      the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in
      the medulla. CONCLUSIONS: Mutations in the TP53 gene are frequent in
      adrenocortical carcinomas and might be used as a marker of malignancy. In the
      normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a
      role in adrenal differentiation.

PMID- 11454519
TI  - Effects of IGF-I and -II, IGF binding protein-3 (IGFBP-3), and transforming
      growth factor-beta (TGF-beta) on growth and apoptosis of human osteosarcoma Saos
      2/B-10 cells: lack of IGF-independent IGFBP-3 effects.
AB  - OBJECTIVE: Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits cell
      growth. Previous reports have suggested the existence of plasma membrane IGFBP-3
      receptors that could mediate direct, IGF-independent effects. Thus far, however,
      the only well-defined putative IGFBP-3 receptor is the type V transforming growth
      factor-beta (TGF-beta) receptor, a membrane glycoprotein that mediates TGF-beta
      induced growth inhibition in selected cells. The aim of the study was to test
      whether IGFBP-3 and TGF-beta exert short-term effects in an osteosarcoma cell
      line that produces no IGF but contains type 1 IGF receptors. DESIGN: DNA
      synthesis and apoptosis in Saos-2/B-10 cells were measured in response to IGF-I,
      IGF-II, IGFBP-3 and TGF-beta2, and to type 1 IGF receptor ligands with poor
      affinity for IGFBP-3 ([QAYL]-IGF-I and insulin). RESULTS: IGF-I and IGF-II
      stimulated thymidine incorporation into DNA and suppressed apoptosis in a dose
      dependent manner with maximal effects at 1 and 3 nM respectively. TGF-beta2
      slightly increased thymidine incorporation into DNA but had no effect on
      apoptosis. IGFBP-3 had no effect by itself. Whereas it blocked the above effects
      of 1 nmol/l IGF-I, it did not block those of 1 nmol/l [QAYL]-IGF-I or 100 nmol/l
      insulin. CONCLUSIONS: IGFBP-3 does not affect DNA synthesis or apoptosis in an
      IGF-independent manner in IGF-responsive osteosarcoma cells. It therefore appears
      to act essentially by sequestration of IGF.

PMID- 11454520
TI  - Overnight dexamethasone suppression of cortisol is associated with
      radiocholesterol uptake patterns in adrenal incidentalomas.

PMID- 11454521
TI  - The crucial role of immunophenotyping in hematology and oncology.

PMID- 11454522
TI  - New methodologic approaches for immunophenotyping acute leukemias.
AB  - BACKGROUND AND OBJECTIVES: Flow cytometry is nowadays the preferred method for
      immunophenotypic identification, enumeration and characterization of blast cells
      at diagnosis. Despite widespread application of standardized protocols, inter
      laboratory reproducibility has still not been achieved. The complexity of
      diagnosis and evaluation of minimal residual disease, in immunophenotyping acute
      leukemia, demands the use of a test that provides all the necessary information.
      DATA SOURCES AND METHODS: The information given here is derived from the
      experience of the authors and from literature files. The most relevant studies
      with adequate conclusions were considered. We report on the current status of
      multiparametric immunophenotyping using simultaneous three and four-color
      staining and the applications of this technique. RESULTS: Multiparametric
      immunophenotyping is a powerful method for achieving a clear discrimination
      between normal and pathologic cells. The specific identification of leukemic
      cells by immunologic gating forms the basis for immunophenotypic diagnosis,
      classification as well as prognostic evaluation of patients with acute leukemias.
      The performance of the procedure with regards to the panels of reagents and the
      analytic processes, is necessarily different in lymphoblastic and myeloblastic
      leukemias, since the diagnostic questions are different. Phenotypic information
      should be specifically provided for the blast cells and antigen expression should
      preferably be reported in quantitative units and CV. This would allow a
      standardized cross evaluation of immunophenotypic results between different
      investigators and laboratories. INTERPRETATION AND CONCLUSIONS: Recent reports
      indicate that phenotypic aberrations reflect genetic abnormalities of leukemic
      cells and therefore their definition and identification is of clinical relevance
      not only for minimal residual disease monitoring but also for subclassifying
      acute myeloid and lymphocytic leukemias.

PMID- 11454523
TI  - Quantification of human cells in NOD/SCID mice by duplex real-time polymerase
      chain reaction.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was the development of a fast
      and reliable polymerase chain reaction (PCR) assay which quantifies the
      proportion of human cells in immunodeficient chimeric mice, for example
      transplanted with human hematopoietic stem cells. DESIGN AND METHODS: We
      developed a TaqMan chemistry-based, real-time duplex PCR assay to quantify human
      and murine DNA in a single-tube reaction in parallel (HUmu PCR). Two independent
      sets of primers and exonuclease probes, located in the tumor necrosis factor-a
      gene of both species, were selected to amplify specifically human and murine
      genomic DNA. Serial dilutions of defined numbers of human cells in mouse cells
      served to construct calibration curves. The test was applied to NOD/SCID mice
      transplanted with CD34(+) cells isolated from human cord blood and compared to
      FACS analysis. RESULTS: Analysis of DNA from human cells diluted stepwise into a
      fixed number of murine cells - and vice versa - led to calibration curves with
      good correlation for human and murine cells (r(2)>0.99) with a detection limit of
      2% human cells. Results obtained with the HUmu PCR paralleled those of FACS
      analysis. However, in contrast to FACS analysis, which requires fresh single cell
      suspensions, the HUmu PCR can be carried out on already stored samples, even from
      solid organs and, moreover, the quantity of material required for analysis is
      very low. INTERPRETATION AND CONCLUSIONS: The HUmu PCR presented here is the
      first real-time PCR assay for simultaneous quantification of human and murine
      cells. It is extremely fast, accurate and is an interesting alternative method
      for quantifying the proportion of human DNA in organs of chimeric mice.

PMID- 11454524
TI  - Valproic acid, trichostatin and their combination with hemin preferentially
      enhance gamma-globin gene expression in human erythroid liquid cultures.
AB  - BACKGROUND AND OBJECTIVES: In addition to conventional therapy, current treatment
      of thalassemia and sickle cell anemia includes inducers of hemoglobin F synthesis
      (hydroxyurea, erythropoietin, azacytidine and butyrate). However, because of
      concerns about the dose-limiting myelotoxicity, potential carcinogenicity and
      high cost of the above agents, an intensive search for less toxic or more
      effective drugs is ongoing. In this study we tested the effect of valproic acid
      and trichostatin, alone or in combination with hemin, on gamma chain synthesis in
      human erythroid liquid cultures. DESIGN AND METHODS: The agents were tested on
      erythroid human liquid cultures derived from normal peripheral blood, peripheral
      blood from beta(s)/beta(thal) patients, normal cord blood and normal bone marrow
      samples. The effect of the agents was expressed as increase of gamma/gamma+beta m
      RNA, measured with competitive reverse transcriptase-polymerase chain recation
      (RT-PCR), or as increase of HbF, measured by high performance liquid
      chromatography (HPLC). RESULTS: Addition of valproic acid or trichostatin to
      human erythroid cell cultures preferentially enhanced gamma mRNA synthesis in all
      blood samples (2.9 to 3.5-fold). The addition of hemin enhanced the effect up to
      10-fold. INTERPRETATION AND CONCLUSIONS: Valproic acid, trichostatin and their
      combination with hemin (all three FDA-approved drugs) preferentially increase
      gamma-globin chain synthesis and may be helpful for the treatment of
      hemoglobinopathies.

PMID- 11454525
TI  - Molecular analysis of patients with relapsed or refractory intermediate-high
      grade non-Hodgkin's lymphoma with bone marrow infiltration undergoing peripheral
      blood progenitor cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: IgH gene rearrangement studies with a polymerase chain
      reaction (PCR) technique can detect the persistence of clonal cells at molecular
      level during the remission phase. This persistence of clonal cells can be used to
      establish the relationship between minimal residual disease (MRD) and clinical
      outcome. We have developed a three-step single strand conformational polymorphism
      PCR strategy which is able to detect clonal B lymphoid cells at a frequency as
      low as 1 clonal cell in 10(6) normal cells. DESIGN AND METHODS: Twenty patients
      with intermediate or high-grade B non-Hodgkin's lymphoma (NHL) were evaluated.
      Patients were pre-treated with a median of two (range 1-4) conventional
      chemotherapy lines before high-dose cyclophosphamide (HDCY). All patients had
      their bone marrow (BM) involved by disease (median 10%; range 5-50%). Nineteen
      patients were offered high-dose therapy followed by peripheral blood progenitor
      cells (PBPC) autografting. RESULTS: MRD analysis was performed for each patient
      at the end of conventional chemotherapy and every three months after high dose
      therapy. All these patients achieved complete response (CR) after high dose
      therapy (HDT). Six patients relapsed after a median time of 24.5 months. All the
      studied apheresis samples were positive at the molecular analysis. All 6 patients
      still positive at the molecular analysis after PBPC autografting relapsed. The
      remaining 13 patients who were negative maintained CR. INTERPRETATION AND
      CONCLUSIONS: Whereas the detection of clonal cells in the apheresis samples did
      not predict an unfavorable outcome, the disappearance of the clonal rearranged
      band from the BM sample after HDT proved to be a favorable prognostic factor and
      was associated with long-lasting disease-free status

PMID- 11454526
TI  - Post-transplant lymphomas: a 20-year epidemiologic, clinical and pathologic study
      in a single center.
AB  - BACKGROUND AND OBJECTIVES: To study the incidence, clinical presentation,
      pathologic features and outcome of post-transplant lymphomas (PTL) during the
      past 20 years. DESIGN AND METHODS: We undertook a descriptive study of all biopsy
      proven cases of PTL diagnosed in our hospital from 1979 through 1999. The average
      annual incidence rate of PTL was analyzed at 5-year intervals from 1979 to 1999.
      Risk ratios were estimated by comparing the incidence of PTL among transplanted
      patients with that of lymphoma observed in the general population of the region.
      Survival analysis was performed at the univariate level using the Kaplan Meier
      technique and at the multivariate level by Cox hazard models. RESULTS: Seventeen
      of 1,860 transplanted patients developed a PTL (0.9%). The risk of PTL was
      calculated to be almost 8-fold higher than the risk of lymphoma in the general
      population. The risk was highest among those who had received a heart transplant
      (RR=35.6). The mean time between transplant and the diagnosis of PTL was 31 +/-
      29 months. Of all PTL, 88% were of B-cell origin and 53% of the cases tested were
      Epstein-Barr virus (EBV)-positive. The median survival was 24 months. The
      majority of patients with allograft involvement died within the 2 months
      following diagnosis (hazard ratio 5.3; 95% CI 1.4-20.7). INTERPRETATION AND
      CONCLUSIONS: Organ transplantation is a major risk factor for the development of
      lymphoma, a disease with a particularly bad prognosis when it develops at the
      site of the allograft. Early diagnosis and more specific treatment may improve
      PTL survival.

PMID- 11454527
TI  - Multivariate analysis of factors influencing quality of life and utility in
      patients with haemophilia.
AB  - BACKGROUND AND OBJECTIVES: Although several studies have determined quality of
      life (QOL) in patients with hemophilia, generic questionnaires have rarely been
      used. The objectives of our study were; 1) to measure QOL and utility in patients
      with hemophilia using the Short Form 36 (SF-36) and the EuroQOL questionnaires;
      2) to evaluate the influence of some clinical variables on QOL and utility; 3) to
      assess the correlation between the two questionnaires. DESIGN AND METHODS: All
      consecutive patients with hemophilia were asked to complete the SF-36 and the
      EuroQOL questionnaires. The following information was recorded from each patient:
      age, type of hemophilia, severity of disease, HCV and HIV infection, number of
      bleeding episodes and cumulative dose of coagulation factors over the previous
      year. These items were entered into a multivariate analysis to assess their
      effect on QOL. Correlation analyses were conducted to evaluate the relationship
      between the EuroQOL and SF-36. RESULTS: Fifty-six patients completed the SF-36
      and the EuroQOL questionnaires. The mean scores of the SF-36 ranged from 55.2
      (general health) to 74.7 (social functioning). The EuroQOLself-classifier and the
      EuroQOLvas showed a mean score of 0.67 (SD=0.26) and 0.66 (SD=0.17),
      respectively. Among the clinical variables, age significantly influenced both the
      EuroQOL and the SF-36 scores. The EuroQOL indices showed a statistically
      significant correlation with each dimension of the SF-36. INTERPRETATION AND
      CONCLUSIONS: Our study quantified the degree to which QOL is impaired in patients
      with hemophilia by using both a generic questionnaire and a utility-based
      approach.

PMID- 11454528
TI  - Effects of unfractionated and low molecular weight heparins on plasma levels of
      hemostatic factors in patients with acute coronary syndromes.
AB  - BACKGROUND AND OBJECTIVES: Unfractionated heparin (UFH) and enoxaparin (low
      molecular weight heparin) constitute fundamental therapies in the treatment of
      patients with acute coronary syndrome (ACS). Since enoxaparin appears to offer
      clinical advantages over UFH in managing ACS, markers of thrombin generation,
      endothelial function and acute phase response could manifest different responses
      to UFH or enoxaparin. The purpose of the present study was to investigate the
      effect that treatment with either UFH or enoxaparin has on plasma hemostatic
      markers in 24 patients with ACS. DESIGN AND METHODS: The patients were randomized
      to receive 5,000 IU intravenous bolus and continuous infusion of 18 IU/Kg/h UFH
      (n=11) or 1 mg/kg/12h subcutaneous enoxaparin (n=13). The plasma levels of
      fibrinogen (Fg), prothrombin fragment 1+2 (F1+2), thrombin antithrombin complex
      (TAT), von Willebrand factor (vWF), tissue factor (TF) and tissue factor pathway
      inhibitor (TFPI) were assayed at admission and 6, 12, 24 and 48 hours after
      heparin treatment. RESULTS: Upon admission, UFH and enoxaparin patients showed a
      significant increase in all the hemostatic parameters measured with respect to
      the levels in the control subjects. In comparison with the baseline levels of the
      UFH- and enoxaparin-treated patients, Fg showed a significant increase at 48 h
      and TFPI at 6, 12 and 24 hours. However, at 48 hours TFPI levels were not
      significantly higher than the basal values. There were no significant changes in
      F1+2, TAT, vWF or TF. INTERPRETATION AND CONCLUSIONS: Markers of thrombin
      generation, endothelial function and acute-phase reactants manifest a similar
      response to UFH and enoxaparin. An increase in thrombin generation may be a
      result of persistently activated inflammatory and endothelial processes, despite
      UFH and enoxaparin treatment.

PMID- 11454529
TI  - The combination of thrombophilic genotypes is associated with definite
      antiphospholipid syndrome.
AB  - BACKGROUND AND OBJECTIVES: Thrombosis and pregnancy morbidity are clinical
      features of the definite antiphospholipid syndrome (APS). These clinical
      complications are also associated with the presence of inherited thrombophilias.
      Interactions between acquired and genetic risk factors are becoming increasingly
      related to a higher thrombotic risk. The aim of our study was to determine the
      prevalence of four common gene polymorphisms in patients with antiphospholipid
      antibodies (aPL). DESIGN AND METHODS: A series of 105 consecutive unselected
      patients with aPL grouped as having APS (n= 69) and not having APS (n= 36) was
      studied. A control group of 200 healthy subjects was also investigated for the
      presence of factor V Leiden (FVL), the 20210A allele of the prothrombin (PT
      20210A) gene, the thermolabile variant (677TT) of methylenetetrahydrofolate
      reductase (MTHFR), and the 4G/4G genotype of the plasminogen activator inhibitor
      (PAI-1) promoter. RESULTS: Two patients who belong to the APS group carried the
      FVL while PT-20210A was found in 6 patients with APS (8.7%) and in 1 of the non
      APS group (2.8%). The prevalence of FVL was similar to that found in the control
      group whereas PT-20210A was significantly more frequent in APS patients than in
      normal controls (2.0%, p=0.02). The MTHFR-677TT was found in 22.0%, 15.1% and
      13.0%, and the PAI-1 (4G/4G) in 27.5%, 22.8% and 23.5% of APS, non-APS patients
      and normal controls, respectively. Furthermore, combinations of PT-20210A or FVL
      with PAI-1 (4G/4G) were significantly more frequent in APS patients (5.8%) than
      in normal controls (0.5%, p=0.016). This difference was not found between non-APS
      patients and normal subjects. INTERPRETATION AND CONCLUSIONS: Present data
      indicate that testing for heritable thrombophilia would be important to identify
      aPL subjects with an increased risk of developing APS.

PMID- 11454530
TI  - Provision of phenotype-matched blood units: no need for pre-transfusion antibody
      screening.
AB  - BACKGROUND AND OBJECTIVES: The Hong Kong government is planning to introduce an
      electronic smart identity card for all seven million citizens in 2003. If the
      smart card contains the full red cell phenotype/genotype of the individual, it
      may be possible to transfuse phenotype-matched blood units without pre
      transfusion antibody screening. We conducted a feasibility study. DESIGN AND
      METHODS: Red cell phenotype was determined for 407 donor blood units and 493
      patients for whom an antibody screen had been ordered. The computer program
      selected phenotype-matched blood from the donor stock for the patients according
      to actual transfusion request. For patients with a positive antibody screen, full
      crossmatching was carried out with the computer-selected phenotype units. The
      frequencies of the various red cell phenotypes in the population were calculated
      from Red Cross data of antigen frequencies. The probabilities of finding at least
      one unit of phenotype-matched blood from a 300-unit hospital stock and a 4,000
      unit Red Cross stock were determined for each phenotype. Cost analysis was
      performed. RESULTS: Ninety-two out of 493 patients received a total of 395 blood
      units. The required number of phenotype-matched blood units could be found for 92
      patients using a 300-unit pool and for all patients using a 4,000-unit pool. We
      calculated that phenotype-matched blood could be provided for more than 98% of
      patients without antibody screening. The total cost of the project is US$ 98
      million with potential savings of US$ 14 million per year. INTERPRETATION AND
      CONCLUSIONS: It is feasible and cost-effective to transfuse patients with
      phenotype-matched blood without antibody screening using a smart card system.

PMID- 11454531
TI  - Bedside leukoreduction of cellular blood components in preventing cytomegalovirus
      transmission in allogeneic bone marrow transplant recipients: a retrospective
      study.
AB  - BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) infection continues to be a
      major complication of bone marrow transplants (BMTs). Administration of
      leukoreduced unscreened cellular blood products at the bedside has been shown to
      be effective in preventing CMV transmission via transfusions in CMV-seronegative
      bone marrow transplant recipients who receive their transplants from CMV
      seronegative donors. The aim of this study was to determine whether CMV infection
      occurred in CMV-seronegative BMT patients who received CMV-seronegative donor
      marrows and CMV untested blood products leukodepleted at the bedside. DESIGN AND
      METHODS: We collected data over a 2-year period from patients undergoing
      allogeneic transplantation who received leukoreduced cellular blood components
      that were not screened for CMV. All CMV-seropositive patients and donors were
      excluded from the study. The CMV status of both the donors and the patients was
      determined before the transplantations. CMV cultures of urine, blood buffy coat,
      bone marrow samples and bronchial washings were performed if necessary in
      patients. RESULTS: Thirty-six CMV-seronegative patient-donor pairs were included
      in the study. Five patients (13.89%) were serologically reactive, but their CMV
      cultures were negative and they did not show signs or symptoms of CMV infection.
      These patients received intravenous immunoglobulin and thus could have acquired
      anti-CMV passively. INTERPRETATION AND CONCLUSIONS: The confidence interval in
      this study is 0/36 incidence of CMV infection. Our present findings support those
      of prior studies showing the effectiveness of filtered unscreened blood
      components as an alternative transfusion support for CMV-seronegative marrow
      transplant recipients. Studies in larger number of patients are warranted.

PMID- 11454532
TI  - Effects of recombinant human granulocyte-macrophage colony-stimulating factor in
      an intensive treatment program for children with Ewing's sarcoma.
AB  - BACKGROUND AND OBJECTIVES: A treatment program including polychemotherapy at
      progressively escalating doses and sequential hemi-body irradiation (HBI) was
      adopted between 1987-1994 at our Pediatric Unit for high risk Ewing's sarcoma.
      Granulocyte-macrophage colony-stimulating factor (GM-CSF) was added to the
      treatment program in a phase II study fashion to evaluate, in a pediatric
      setting, its tolerability, as well as its impact on drug dose escalation and on
      the need for supportive care. DESIGN AND METHODS: The study was open-label and
      sequential; GM-CSF administration (5 microg/Kg s.c./d x10) was planned after each
      chemotherapy cycle and after each HBI session in 18 consecutive patients (group
      A). Thirty-eight additional patients (group B) were treated by the same
      therapeutic program, without GM-CSF. In 12 patients (6 in each group) long-term
      bone marrow cultures (LTBMC) were performed to evaluate the myeloproliferative
      potential throughout the chemotherapeutic program. RESULTS: Seven of 18 (39%)
      patients experienced side effects from GM-CSF; 3/7 discontinued GM-CSF due to
      anaphylactic symptoms. The degree of neutropenia, as well as the frequency of
      infectious episodes and the need for supportive care were significantly lower in
      group A than in group B. Iatrogenic thrombocytopenia, and the possibility of
      performing drug-dose escalation were similar in the two groups. The 5-year event
      free survival probabilities for group A and B were similar. LTBMC showed that the
      chemotherapy-related depletion of myeloid precursors could be more pronounced in
      patients receiving GM-CSF cyclically. INTERPRETATION AND CONCLUSIONS: In this
      series, GM-CSF was shown to be effective on iatrogenic neutropenia and related
      complications, with no impact on thrombopoiesis, drug dose escalation and
      outcome.

PMID- 11454533
TI  - Prospective evaluation of primary infection due to HCV, HGV or TTV in children
      with newly diagnosed neoplasia.

PMID- 11454534
TI  - CD56 expression could be associated with monocytic differentiation in acute
      myeloid leukemia with t(8;21).

PMID- 11454535
TI  - Myeloid natural killer cell leukemia resembling a variant of acute promyelocytic
      leukemia.

PMID- 11454536
TI  - Extramedullary relapse of acute lymphoblastic leukemia in the breast after
      allogeneic stem cell transplantation and concomitant persistence of donor
      hematopoiesis.

PMID- 11454537
TI  - Polycythemia vera and essential thrombocythemia with monoclonal gammopathy:
      experience of a single institution.

PMID- 11454538
TI  - Serum levels of vascular endothelial growth factor in chronic leukemias. A
      comparative study with emphasis on myeloproliferative disorders.

PMID- 11454539
TI  - Thalidomide therapy in compensated and decompensated myelofibrosis with myeloid
      metaplasia.

PMID- 11454540
TI  - High circulating tumor necrosis factor levels correlate with increased evels of
      soluble CD14 in patients with non-Hodgkin's lymphoma.

PMID- 11454541
TI  - High, intermittent dose of all-trans retinoic acid in combination with alpha
      interferon for advanced multiple myeloma.

PMID- 11454542
TI  - Detection of ICAM-1, ICAM-2, ICAM-3, PECAM-1 and VCAM-1, evaluation of
      hypercoagulable state and platelet aggregation in hemoglobinopathy patients with
      erythroblasts.

PMID- 11454543
TI  - Reduced intensity regimen for a second mismatched transplant.

PMID- 11454544
TI  - Long-term follow-up of human herpes virus 6 infection in autologous bone marrow
      transplant recipients.

PMID- 11454545
TI  - The irreplaceable image: Rapidly growing extramedullary hematopoiesis in lymph
      nodes: unusual findings of long-standing idiopathic myelofibrosis.

PMID- 11454547
TI  - Muscle metaboreflex control is diminished in normotensive obese women.
AB  - There is no information about the muscle metaboreflex control in obese
      individuals. In 40 normotensive obese women (OW; body mass index 33.5 +/- 0.4
      kg/m2, age 32.4 +/- 1.1 yr) and 15 age-matched, normotensive lean women (LW; body
      mass index 22.7 +/- 0.8 kg/m2, age 34.4 +/- 1.4 yr), we measured muscle
      sympathetic nerve activity (MSNA) and forearm blood flow (FBF) in the
      nonexercising forearm during static exercise at 10 and 30% of maximal voluntary
      contraction (MVC). Baseline MSNA (38 +/- 2 vs. 31 +/- 1 bursts/min, P = 0.001)
      and mean blood pressure were significantly higher in OW compared with LW. FBF was
      significantly lower, whereas forearm vascular resistance was significantly higher
      in OW. During 10% MVC, MSNA increased similarly in both groups, but during 30%
      MVC, MSNA was higher in LW. FBF and forearm vascular resistance responses during
      both 10 and 30% MVC were similar between groups. During posthandgrip circulatory
      arrest, MSNA remained significantly elevated compared with baseline in both
      groups, but this increase was significantly lower in OW (3.8 +/- 0.82 vs. 9.4 +/-
      1.03 bursts/min, P = 0.002). In conclusion, muscle metaboreflex control of MSNA
      is blunted in OW. MSNA responses are not augmented during selective activation of
      central command/mechanoreceptors and metaboreceptors, despite increased MSNA
      levels in OW. Muscle vasodilatory response during graded handgrip isometric
      exercise is preserved in OW.

PMID- 11454548
TI  - Isolated ventricular myocytes from copper-deficient rat hearts exhibit enhanced
      contractile function.
AB  - Dietary copper deficiency leads to cardiac hypertrophy, cardiac fibrosis,
      derangement of myofibrils, and impaired cardiac contractile and
      electrophysiological function. The purpose of this study was to determine whether
      impaired cardiac function from copper deficiency is due to depressed contractile
      function at the single myocyte level. Male Sprague-Dawley rats were fed diets
      that were either copper adequate (5.59-6.05 microg copper/g body wt; n = 11) or
      copper deficient (0.29-0.34 microg copper/g body wt; n = 11) for 5 wk.
      Ventricular myocytes were dispersed and mechanical properties were evaluated
      using the SoftEdge video-based edge-detection system. Intracellular Ca2+
      transients were examined using fura 2-acetoxymethyl ester. Myocytes were
      electrically stimulated to contract at 0.5 Hz. Properties evaluated included peak
      shortening (PS), time to peak shortening (TPS), time to 90% relengthening (TR90),
      and maximal velocities of shortening and relengthening (+/-dL/dt). Myocytes from
      the copper-deficient rat hearts exhibited significantly enhanced PS values
      associated with shortened TR90 measurements compared with those from copper
      adequate rat hearts. The +/-dL/dt values were enhanced and the intracellular Ca2+
      transient decay rate was depressed in myocytes from copper-deficient rats. These
      data indicate that impaired cardiac contractile function that is seen in copper
      deficient whole hearts might not be due to depressed cardiac contractile function
      at the single cell level but rather to other mechanisms such as cardiac fibrosis.

PMID- 11454549
TI  - Tetrahydrobiopterin levels regulate endothelial cell proliferation.
AB  - Vascular abnormalities, including altered angiogenesis, are major factors
      contributing to the morbidity and mortality of diabetes. We hypothesized that
      impaired angiogenesis in diabetes results from decreased tetrahydrobiopterin
      (BH4)-dependent synthesis of nitric oxide (NO) by endothelial cells (EC). To test
      this hypothesis, we utilized EC from spontaneously diabetic BB (BBd) and
      nondiabetes-prone BB (BBn) rats to investigate the link between BH4 and EC
      proliferation. There were significant decreases in the proliferation rate and
      expression of proliferating cell nuclear antigen in BBd versus BBn EC, with no
      evidence of apoptosis in either group. Sepiapterin (a precursor of BH4 via the
      salvage pathway) increased BH4 synthesis and enhanced proliferation of BBd EC.
      The stimulating effect of sepiapterin on EC proliferation was attenuated by NG
      monomethyl-L-arginine, a NO synthase inhibitor. Reducing BH4 concentrations in
      BBn EC caused a decrease in proliferation, which was attenuated by a long-acting
      NO donor. Our results suggest that BH4 levels regulate proliferation of normal EC
      and that a BH4 deficiency impairs NO-dependent proliferation of BBd EC.

PMID- 11454550
TI  - Purkinje and ventricular contributions to endocardial activation sequence in
      perfused rabbit right ventricle.
AB  - Interactions between peripheral conduction system and myocardial wave fronts
      control the ventricular endocardial activation sequence. To assess those
      interactions during sinus and paced ventricular beats, we recorded unipolar
      electrograms from 528 electrodes spaced 0.5 mm apart and placed over most of the
      perfused rabbit right ventricular free wall endocardium. Left ventricular
      contributions to electrograms were eliminated by cryoablating that tissue.
      Electrograms were systematically processed to identify fast (P) deflections
      separated by >2 ms from slow (V) deflections to measure P-V latencies. By using
      this criterion during sinus mapping (n = 5), we found P deflections in 22% of
      electrograms. They preceded V deflections at 91% of sites. Peripheral conduction
      system wave fronts preceded myocardial wave fronts by an overall P-V latency
      magnitude that measured 6.7 +/- 3.9 ms. During endocardial pacing (n = 8) at 500
      ms cycle length, P deflections were identified on 15% of electrodes and preceded
      V deflections at only 38% of sites, and wave fronts were separated by a P-V
      latency magnitude of 5.6 +/- 2.3 ms. The findings were independent of apical,
      basal, or septal drive site. Modest changes in P-V latency accompanied cycle
      length accommodation to 125-ms pacing (6.8 +/- 2.6 ms), although more pronounced
      separation between wave fronts followed premature stimulation (11.7 +/- 10.4 ms).
      These results suggested peripheral conduction system and myocardial wave fronts
      became functionally more dissociated after premature stimulation. Furthermore,
      our analysis of the first ectopic beats that followed 12 of 24 premature stimuli
      revealed comparable separation between wave fronts (10.7 +/- 5.5 ms), suggesting
      the dissociation observed during the premature cycles persisted during the
      initiating cycles of the resulting arrhythmias.

PMID- 11454551
TI  - Regional septal dysfunction in a three-dimensional computational model of focal
      myofiber disarray.
AB  - MLC2v/ras transgenic mice display a phenotype characteristic of hypertrophic
      cardiomyopathy, with septal hypertrophy and focal myocyte disarray. Experimental
      measurements of septal wall mechanics in ras transgenic mice have previously
      shown that regions of myocyte disarray have reduced principal systolic
      shortening, torsional systolic shear, and sarcomere length. To investigate the
      mechanisms of this regional dysfunction, a three-dimensional prolate spheroidal
      finite-element model was used to simulate filling and ejection in the
      hypertrophied mouse left ventricle with septal disarray. Focally disarrayed
      septal myocardium was modeled by randomly distributed three-dimensional regions
      of altered material properties based on measured statistical distributions of
      muscle fiber angular dispersion. Material properties in disarrayed regions were
      modeled by decreased systolic anisotropy derived from increased fiber angle
      dispersion and decreased systolic tension development associated with reduced
      sarcomere lengths. Compared with measurements in ras transgenic mice, the model
      showed similar heterogeneity of septal systolic strain with the largest
      reductions in principal shortening and torsional shear in regions of greatest
      disarray. Average systolic principal shortening on the right ventricular septal
      surface of the model was -0.114 for normal regions and -0.065 for disarrayed
      regions; for torsional shear, these values were 0.047 and 0.019, respectively.
      These model results suggest that regional dysfunction in ras transgenic mice may
      be explained in part by the observed structural defects, including myofiber
      dispersion and reduced sarcomere length, which contributed about equally to
      predicted dysfunction in the disarrayed myocardium.

PMID- 11454552
TI  - Protection of ischemic myocardium in diabetics by inhibition of electroneutral
      Na+-K+-2Cl- cotransporter.
AB  - Diabetes increases both the incidence of cardiovascular disease and complications
      of myocardial infarction and heart failure. Studies using diabetic animals have
      shown that changes in myocardial sodium transporters result in alterations in
      intracellular sodium (Na(i)) homeostasis. Because the changes in sodium
      homeostasis can be due to increased entry of Na+ via the electroneutral Na+-K+
      2Cl- cotransporter (NKCC), we conducted experiments in acute diabetic hearts to
      determine if 1) net inward cation flux via NKCC is increased, 2) this
      cotransporter contributes to a greater increase in Na(i) during ischemia, and 3)
      inhibition of NKCC limits injury and improves function after ischemia
      reperfusion. These issues were investigated in perfused type I diabetic and
      nondiabetic rat hearts subjected to ischemia and 60 min of reperfusion. A group
      of diabetic and nondiabetic hearts was perfused with 5 microM of bumetanide, an
      inhibitor of NKCC. Flux via NKCC, Na(i), and ATP was measured in each group with
      the use of radiotracer 86Rb, 23Na, and 31P nuclear magnetic resonance
      spectroscopy, respectively, whereas ischemic injury was assessed by measuring
      creatine kinase release on reperfusion. Cation flux via NKCC, as measured by 86Rb
      uptake, was significantly increased in diabetic hearts. Inhibition of NKCC
      significantly reduced ischemic injury in diabetic hearts, improved functional
      recovery on reperfusion, attenuated the ischemic rise in Na(i), and conserved ATP
      during ischemia-reperfusion. Parallel studies in nondiabetic hearts showed that
      NKCC inhibition was not cardioprotective. These findings demonstrate that flux
      via NKCC is increased in type I diabetic hearts and that inhibition with
      bumetanide attenuates changes in Na(i) and ATP during ischemia and protects
      against ischemic injury. The data suggest a therapeutic role for pharmacological
      agents that inhibit flux via NKCC in diabetic patients with myocardial ischemia.

PMID- 11454553
TI  - Mitogen-activated protein kinases mediate heat shock-induced delayed protection
      in mouse heart.
AB  - We determined the role of p38 mitogen-activated protein kinase (MAPK), 72-kDa
      heat shock protein (HSP72), and antioxidant enzymes in whole body heat stress
      (HS)-induced cardioprotection in mouse hearts. Adult male mice were treated with
      either HS or anesthesia only. At 0.5, 48, 72, or 120 h later, the hearts were
      subjected to 20 min of global ischemia and 30 min of reperfusion in Langendorff
      mode. A significant protection against ischemia-reperfusion injury was observed
      48 h after HS as demonstrated by: 1) reduction in infarct size; 2) decrease in
      leakage of lactate dehydrogenase; and 3) enhanced postischemic ventricular
      contractile function. No such protection was observed at other post-HS time
      points. HS caused an ~25% increase in phosphorylated c-Jun NH2-terminal kinase
      (JNK) but not p38 MAPK in the heart during the first 2-h post-HS time period.
      Cardioprotection was abolished by the MAPK inhibitor SB-203580, which also
      partially suppressed the HS-induced JNK phosphorylation. The protective effect
      was associated with a two- to threefold increase in HSP72 protein accumulation,
      but not antioxidant enzyme activities (catalase and Cu/Zn and Mn SOD) in the
      myocardium. Although HSP72 levels remained high 72 h after HS, the
      cardioprotection had already disappeared. We conclude that HS induces a transient
      delayed cardioprotection at 48 h after thermal stress in mice which appears to be
      mediated via a MAPK-signaling pathway.

PMID- 11454554
TI  - Optical measurement of cell-to-cell coupling in intact heart using subthreshold
      electrical stimulation.
AB  - Electrical coupling between myocytes plays a critical role in propagation,
      repolarization, and arrhythmias. On the basis of predictions from cable theory,
      we hypothesized that the cardiac space constant (lambda) measured from the decay
      of subthreshold transmembrane potential (ST-Vm) in space would provide an index
      of regional cell-to-cell coupling in the intact heart. With the use of voltage
      sensitive dyes, the distribution of ST-Vm was measured from hundreds of sites in
      close proximity to the site of subthreshold stimulation. lambda was calculated
      from the exponential decay of ST-Vm in space. Consistent with known directional
      differences in axial resistance, the spatial distribution of ST-Vm was strongly
      dependent on fiber orientation, because lambda was significantly (P < 0.001)
      longer along (1.5 +/- 0.1 mm) compared with across (0.8 +/- 0.1 mm) fibers. There
      was a close linear relationship (P < 0.001) between conduction velocity (CV) and
      lambda along all fiber angles tested. Reducing gap junctional conductance by
      heptanol reversibly decreased CV and lambda in parallel by approximately 50%. In
      contrast, sodium channel blockade by flecainide slowed CV by 40% but had no
      effect on lambda, reaffirming that lambda was an index of passive but not active
      membrane properties. These data establish the feasibility of measuring lambda as
      an index of cell-to-cell coupling in the intact heart, and indicate strong
      dependency of lambda on fiber orientation and pharmacological alterations of gap
      junction conductance.

PMID- 11454555
TI  - Matrix metalloproteinase expression and activity in isolated myocytes after
      neurohormonal stimulation.
AB  - Changes in myocardial matrix metalloproteinase (MMP) activity and expression have
      been associated with left ventricular (LV) remodeling. A recent study
      demonstrated that LV myocytes synthesize and release MMPs, which suggests that LV
      myocytes may participate in myocardial remodeling. However, extracellular stimuli
      that may potentially influence LV myocyte MMP production remains to be defined.
      In the present study MMP activity and expression were measured in porcine LV
      myocyte preparations (10(5) total cells; n = 6) following incubation (6 h) with
      endothelin-1 (ET-1;50 pM), angiotensin II (ANG II; 1 microM), or the beta
      receptor agonist isoproterenol (Iso; 10 nM). LV myocyte-conditioned media were
      then subjected to gelatin zymography and an MMP-2 antibody capture assay. MMP
      zymographic gelatinase activity and MMP-2 content were increased by over 40% in
      LV myocyte-conditioned media after incubation with ET-1 or ANG II (P < 0.05).
      Exposure to the phorbol ester phorbol 12-myristate 13-acetate (PMA; 50 ng/ml)
      resulted in a 30% increase in zymographic gelatinase activity and a 63% increase
      in MMP-2 content (P < 0.05), suggesting that protein kinase C activation may be
      an intracellular mechanism for MMP induction. With the use of a confocal
      microscopy, membrane type-1 MMP (MT1-MMP) was localized to porcine LV myocytes,
      and immunoblotting for MT1-MMP using LV myocyte extracts revealed that after
      exposure to Iso, ET-1, ANG II, or PMA (P < 0.05), MT1-MMP abundance increased
      over 50%. Thus stimulation of specific neurohormonal systems that are relevant to
      LV remodeling influences LV myocyte MMP synthesis and release.

PMID- 11454556
TI  - O2-dependent prostanoid synthesis activates functional PGE receptors on corpus
      cavernosum smooth muscle.
AB  - We have previously demonstrated that decreased O2 tension inhibits prostaglandin
      synthesis from human corpus cavernosum smooth muscle cells in static culture over
      8-18 h (R. B. Moreland et al., Molecular Urology 2: 41-47, 1998). In this report,
      an experimental system was designed that allowed determination of the effects of
      O2 tension changes over the time frame of physiological penile erection. Human
      corpus cavernosum smooth muscle cells were cultured on microcarrier beads in
      enclosed stirrer flasks so that rapid changes of O2 tension could be modulated.
      After 18 h of equilibration at 30-40 mmHg to simulate blood PO2 at penile
      flaccidity, O2 tension was increased to 100 mmHg for 1 h and then returned to 30
      40 mmHg. Media samples were withdrawn for prostanoid synthesis and cell samples
      were taken for cAMP determinations. After 18 h of 30-40 mmHg PO2 values,
      prostanoid synthesis by human corpus cavernosum smooth muscle cells was low (0.1
      0.7 pmol/10(6) cells). When PO2 was increased to 100 mmHg, a rapid increase in
      PGE2 >> PGF2alpha > PGD2 was observed (thromboxane A2 was undetectable), which
      peaked at 5.7 pmol PGE2/10(6) cells. Increased O2 tension correlated with
      increased PGE2 and increased intracellular synthesis of cAMP. The prostaglandin
      G/H synthase inhibitor indomethacin or the E prostanoid (EP2)-selective
      antagonist AH-6809 each inhibited the O2-tension-dependent increases in cAMP.
      These data support a role of differential O2 tension in the penis in the smooth
      muscle synthesis of PGE2, which in turn increases cAMP synthesis via EP2
      receptors.

PMID- 11454557
TI  - Contrasting effects of phentolamine and nitroprusside on neural and
      cardiovascular variability.
AB  - The relative contributions of a central neural oscillator and of the delay in
      alpha-adrenergic transmission within the baroreflex loop in the predominance of
      low-frequency (LF) cardiovascular variability during sympathetic activation in
      humans are unclear. We measured R-R interval (RR), muscle sympathetic nerve
      activity (MSNA), blood pressure (BP), and their variability in 10 normal subjects
      during sympathetic activation achieved by BP lowering with sodium nitroprusside
      (SNP) and alpha-adrenergic blockade using phentolamine. SNP and phentolamine
      induced comparable reductions in BP (P > 0.25). Despite tachycardia and
      sympathetic activation with both SNP and phentolamine, LF variability in RR,
      MSNA, and BP increased during SNP and decreased during phentolamine (SNP: RR +20
      +/- 6%, MSNA +3 +/- 5%, systolic BP +9 +/- 6%, diastolic BP +7 +/- 5%;
      phentolamine: RR -2 +/- 7%, MSNA -34 +/- 6%, systolic BP -16 +/- 8%, diastolic BP
      -13 +/- 4%, P < 0.05 except systolic BP, where P = 0.09). Thus LF variability is
      reduced when sympathetic activation is induced by alpha-adrenergic blockade. This
      suggests that alpha-adrenergic transmission within the baroreflex loop may
      contribute importantly to the predominance of LF cardiovascular variability
      associated with sympathetic excitation in humans.

PMID- 11454558
TI  - Sustained high O2 use for Ca2+ handling in rat ventricular slices under decreased
      free shortening after ryanodine.
AB  - We hypothesized that O2 wasting of Ca2+ handling in the excitation-contraction
      coupling in ryanodine-treated failing hearts might derive from an increased
      external Ca2+ extrusion via Na+/Ca2+ exchanger and futile Ca2+ cycling via
      sarcoplasmic reticulum (SR) Ca2+-ATPase. We tested this hypothesis by
      mechanoenergetic studies using rat left ventricular slices. After the slices were
      treated with ryanodine (0.1 microM), 1-Hz free shortening significantly decreased
      by 78-85%, whereas the observed O2 consumption (VO2) required for total Ca2+
      handling, increased from 0.79 to 1.13 ml O2 x min(-1) x 100 g x LV(-1) (155.6% of
      control). We reconfirmed that cyclopiazonic acid (10 microM), a blocker of SR
      Ca2+-ATPase, decreased VO2 by 75-80% in normal slices. However, 100 microM of
      cyclopiazonic acid was needed to inhibit the VO2 by 80% after ryanodine
      treatment. Blockade of a sarcolemmal Na+/Ca2+ exchanger by KB-R7943 (10 microM)
      significantly decreased VO2 by 45% after ryanodine treatment without significant
      effects on normal slices. Our results indicated that the VO2 increase following
      ryanodine treatment was derived from a net change of an increased external Ca2+
      extrusion via Na+/Ca2+ exchanger and futile Ca2+ cycling via SR Ca2+-ATPase.

PMID- 11454559
TI  - Assessment of LV systolic function in atrial fibrillation using an index of
      preceding cardiac cycles.
AB  - The clinical assessment of left ventricular (LV) systolic function during atrial
      fibrillation (AF) is unreliable and difficult because of beat-to-beat
      variability. We evaluated an index for the estimation of LV systolic function in
      AF that is based on the relationship between the preceding (R-R1) and
      prepreceding (R-R2) R-R intervals. LV Doppler stroke volume (SV), ejection
      fraction (EF), peak aortic flow rate (AoF) and the maximum value of the first
      derivative of the LV pressure curve (dP/dt(max)) were evaluated in 13 healthy
      open-chest dogs during triggered AF. All parameters showed a significantly strong
      positive linear relationship with the ratio of R-R1/R-R2 (r = 0.65, 0.74, 0.75,
      and 0.70 for SV, EF, AoF, and dP/dt(max), respectively). The calculated value of
      LV systolic parameters at R-R1/R-R2 = 1 in the linear regression line showed a
      good relationship and an agreement with the measured average value of the
      parameter over all cardiac cycles (SV, 12.1 vs. 12.8 ml; EF, 49.6 vs. 51.2%; AoF,
      1.37 vs. 1.48 l/min; and dP/dt(max), 2,323 vs. 2,454 mmHg/s). Using the LV
      systolic parameters estimated at R-R1/R-R2 = 1 in the linear regression line
      allows the LV contractile function to be accurately and reproducibly evaluated
      during AF and obviates the less-reliable process of averaging multiple cardiac
      cycles.

PMID- 11454560
TI  - Diminished alpha1-adrenergic-mediated contraction and translocation of PKC in
      senescent rat heart.
AB  - Myocardial reserve function declines with aging due in part to reduced alpha- and
      beta-adrenergic receptor (AR)-mediated contractile augmentation. Whereas specific
      age-associated deficits in beta-AR signaling have been identified, it is not
      known which components of the alpha1-AR signaling cascade, e.g., protein kinase C
      (PKC) and associated anchoring proteins (receptors for activated C kinase;
      RACKs), underlie deficits in alpha1-AR contractile function with aging. We
      therefore assessed cardiac contraction (dP/dt) in Langendorff perfused hearts
      isolated from adult (5 mo) and senescent (24 mo) Wistar rats following maximal
      alpha1-AR stimulation with phenylephrine (PE), and we measured the subcellular
      distribution of PKCalpha and PKCepsilon, and their respective anchoring proteins
      RACK1 and RACK2 by Western blotting. The maximum dP/dt response to PE (10(-5) M)
      was significantly reduced by 41% in 24-mo-old vs. 5-mo-old (P < 0.01). Inhibitory
      effects of PKC blockade (chelerythrine; 10 microM) on dP/dt following alpha1-AR
      stimulation with PE observed in adult hearts were absent in 24-mo-old hearts (P <
      0.01). In 5-mo-old hearts, PE elicited reductions in soluble PKCalpha and
      PKCepsilon levels, while increasing particulate PKCalpha and PKCepsilon levels to
      a similar extent. In contrast, soluble PKCalpha and PKCepsilon levels in 24-mo
      old hearts were increased in response to PE; particulate PKCepsilon and PKCalpha
      were unchanged or reduced and associated with significant reductions in
      particulate RACK1 and RACK2. The results indicate, for the first time, that
      selective translocation of PKCalpha and PKCepsilon in response to alpha1-AR
      stimulation is disrupted in the senescent myocardium. That age-related reductions
      in particulate RACK1 and RACK2 levels were also observed provide evidence that
      alterations in PKC-anchoring proteins may contribute to impaired PKC
      translocation and defective alpha1-AR contraction in the aged rat heart.

PMID- 11454561
TI  - Menadione mimics the infarct-limiting effect of preconditioning in isolated rat
      hearts.
AB  - The role of mitochondrial free radicals in the cardioprotective effect of
      ischemic preconditioning was examined in isolated buffer-perfused rat hearts.
      Infarct size in control rat hearts subjected to 30 min of regional ischemia and
      120 min of reperfusion was 32.6 +/- 3.4% of the risk zone. Ischemic
      preconditioning (3 cycles of 5-min global ischemia/5-min reperfusion) before the
      same regional ischemia and reperfusion protocol significantly reduced infarct
      size to 2.6 +/- 0.8% of the risk zone. Perfusion with menadione (3.0 microM), a
      generator of mitochondrial free radicals, in lieu of preconditioning ischemia
      significantly reduced infarction to 10.9 +/- 2.7%. N-2-mercaptopropionylglycine
      (1.0 mM), a free radical scavenger, blocked the protection of menadione,
      significantly increasing infarction to 23.5 +/- 1.1%. Myxothiazol (0.6 microM), a
      site III mitochondrial inhibitor, blocked the protection of menadione and
      significantly increased infarction to 25.2 +/- 3.8%. The infarct-limiting effect
      of menadione was attenuated to 19.7 +/- 1.5% of the risk zone by 10 microM
      SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Furthermore,
      menadione significantly increased p38 MAPK phosphorylation to a level 5.6-fold
      over basal. These results indicate that free radicals that originate within
      mitochondria can activate p38 MAPK and protect hearts against infarction.

PMID- 11454562
TI  - Inotropic response of rabbit ventricular myocytes to endothelin-1: difference
      from isolated papillary muscles.
AB  - Endothelin-1 (ET-1) increased cell shortening and Ca2+ transients over the
      concentration of 3 x 10(-11) M to 10(-9) M with EC50 of 8.3 x 10(-11) M in rabbit
      single ventricular myocytes. Thus ET-1 was approximately 60 times more potent in
      single myocytes than in papillary muscles (EC50 = 5.1 x 10(-9) M) of the same
      species. In single myocytes, ET-1 at 10(-8) M elicited an inhibitory response
      that counteracted the facilitatory response: the concentration-response curve
      (CRC) for ET-1 was bell shaped. The ET(A)-receptor antagonist BQ-485 shifted CRC
      for ET-1 to the right in parallel; however, the facilitatory response to 10(-8) M
      ET-1 was markedly enhanced by BQ-485 and also by the ET(B) antagonist BQ-788. The
      ET(A)/ET(B) antagonist TAK-044 abolished the ET-1-induced response. These
      findings indicate that the response to ET-1 of single myocytes is different from
      that of papillary muscles in concentration dependence, characteristics of the
      response, and susceptibility to ET-receptor antagonists. Anomalous
      pharmacological characteristics of ET-1-induced response in rabbit papillary
      muscles may be due to integrated regulatory mechanisms that may involve also
      various types of noncardiac cell in ventricular myocardium.

PMID- 11454563
TI  - Role of endothelial [Ca2+]i in activation of eNOS in pressurized arterioles by
      agonists and wall shear stress.
AB  - In cultured endothelial cells, Ca2+-dependent and -independent activation of
      nitric oxide (NO) synthesis to agonists and flow/wall shear stress (WSS) has been
      demonstrated. However, the presence and function of these pathways are less well
      known in microvessels that can be exposed to a high level of WSS. We hypothesized
      that the role of changes in endothelial intracellular calcium concentration
      ([Ca2+]i) is different in agonist- and WSS-induced release of NO. Thus changes in
      endothelial [Ca2+]i and diameter of intact pressurized (approximately 100 microm
      at 80 mmHg) gracilis skeletal muscle arterioles of rats were measured by
      fluorescent videomicroscopy. Acetylcholine (ACh) and increases in WSS (by
      increasing intraluminal flow) elicited dilations (maximum 91 +/- 2% and 34 +/-
      4%) that could be inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME), a
      NO synthase blocker. In diameter-clamped arterioles, ACh caused substantial
      increases in the endothelial calcium fluorescence ratio (ER(Ca), maximum 43 +/-
      5%), which was significantly greater than changes in ER(Ca) (maximum
      approximately 10%) to increases in WSS. The Ca(2+) ionophore A-23187 also
      substantially increased ER(Ca) (maximum 38 +/- 5%) and elicited significant L
      NAME-sensitive arteriolar dilations (maximum 45 +/- 7%). Intraluminal
      administration of the tyrosine kinase inhibitor genistein had no effect on
      dilations induced by ACh or the NO donor sodium nitroprusside, whereas it
      eliminated WSS-induced dilations. Collectively, our data suggest that, in
      endothelium of skeletal muscle arterioles, NO synthesis is activated by shear
      stress without a substantial increase in [Ca2+]i, most likely by activation of
      tyrosine kinase pathways, whereas NO release by ACh and A-23187 is associated
      with substantial increases in [Ca2+]i.

PMID- 11454564
TI  - Effects on sympathetic activity of 8-OHDPAT and clonidine in cat medullary
      lateral tegmental field.
AB  - This study was designed to test the hypothesis that 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OHDPAT) and clonidine reduce sympathetic nerve discharge
      (SND) and mean arterial pressure (MAP), in part by actions in the medullary
      lateral tegmental field (LTF). We microinjected these drugs bilaterally into the
      LTF of baroreceptor-innervated and -denervated cats anesthetized with Dial
      urethane. Neither drug altered SND (as quantified by using power spectral
      analysis) or MAP when injected into the LTF of baroreceptor-denervated cats.
      However, cardiac-related power in SND was significantly increased to 148 +/- 12
      (mean +/- SE) and 149 +/- 5% of control by microinjections of 8-OHDPAT (n = 5)
      and clonidine (n = 5), respectively, in baroreceptor-innervated cats whose MAP
      was kept constant; there was no change in 0- to 6-Hz power or total power. SND
      was significantly reduced by microinjection of these drugs into the rostral
      ventrolateral medulla of baroreceptor-innervated and -denervated cats. In
      conclusion, although 8-OHDPAT and clonidine did not reduce SND when injected into
      the LTF, they acted in this region to facilitate baroreceptor reflex control of
      SND, as evidenced by a selective increase in cardiac-related power.

PMID- 11454565
TI  - Cross-sectional area and volume compliance of porcine left coronary arteries.
AB  - We have determined the cross-sectional area (CSA) compliance of the first several
      generations of pig coronary arteries and the volume compliance of the coronary
      arterial tree (vessels >0.5 mm in diameter) using a videodensitometric technique.
      The coronary arteries of four KCl-arrested maximally vasodilated pig hearts were
      perfused with iodine and 3% Cab-O-Sil. Because Cab-O-Sil occludes small arteries,
      the flow can be stopped and the pressure can be maintained while the trunk of the
      coronary artery and its subbranches are imaged using digital angiography. The
      coronary arteries were preconditioned several times with cyclic changes in
      pressure from 0 to 160 mmHg. The pressure was then varied in a triangular
      pattern, and the absolute CSA of each vessel and the total arterial volume were
      calculated using videodensitometry in conjunction with digital subtraction
      angiography. Our results have shown that the pressure-diameter and pressure
      volume relationships are linear in the 60-140 mmHg pressure range. Furthermore,
      the compliance of the coronary arteries is small; i.e., the diameter of the
      coronary artery changes by <15% in the 80-mmHg pressure range. The compliance
      data couples the mechanics of the blood vessel wall to the mechanics of blood
      flow to yield a pressure-flow relationship for each coronary arterial segment.

PMID- 11454566
TI  - Motion of red blood cells in a capillary with an endothelial surface layer:
      effect of flow velocity.
AB  - Interior surfaces of capillaries are lined with macromolecules forming an
      endothelial surface layer (ESL). A theoretical model is used to investigate
      effects of flow velocity on motion and axisymmetric deformation of red blood
      cells in a capillary with an ESL. Cell deformation is analyzed, including effects
      of membrane shear and bending elasticity. Plasma flow around the cell and through
      the ESL is computed using lubrication theory. The ESL is represented as a porous
      layer that exerts compressive forces on red blood cells that penetrate it.
      According to the model, hydrodynamic pressures generated by plasma flow around
      the cell squeeze moving red blood cells into narrow elongated shapes. If the ESL
      is 0.7 microm wide, with hydraulic resistivity of 2 x 10(8) dyn x s x cm(-4), and
      exerts a force of 20 dyn/cm2, predicted variation with flow velocity of the gap
      width between red blood cell and capillary wall agrees well with observations.
      Predicted gap at a velocity of 0.1 mm/s is approximately 0.6 microm vs.
      approximately 0.2 microm with no ESL. Predicted flow resistance increases
      markedly at low velocities. The model shows that exclusion of red blood cells
      from the ESL in flowing capillaries can result from hydrodynamic forces generated
      by plasma flow through the ESL.

PMID- 11454567
TI  - Alpha1-adrenoceptor-Gq-RhoA signaling is upregulated to increase myofibrillar
      Ca2+ sensitivity in failing hearts.
AB  - Alpha1-adrenergic stimulation, coupled to Gq, has been shown to promote heart
      failure. However, the role of alpha1-adrenergic signaling in the regulation of
      myocardial contractility in failing myocardium is still poorly understood. To
      investigate this, we observed 1) the effect of phenylephrine on myofibrillar Ca2+
      sensitivity in alpha-toxin-skinned cardiomyocytes, and 2) protein expression of
      Gq, RhoA, and myosin light chain phosphorylation using tachypacing-induced canine
      failing hearts. Phenylephrine significantly increased myofibrillar Ca2+
      sensitivity in failing but not in normal cardiomyocytes. Whereas Y-27632 (Rho
      kinase inhibitor) blocked the phenylephrine-induced Ca2+ sensitization in the
      failing myocytes, calphostin C (protein kinase C inhibitor) had no effect on Ca2+
      sensitization. The protein expression of Galpha(q) and RhoA and the
      phosphorylation level of regulatory myosin light chain significantly increased in
      the failing myocardium. Our results suggest that alpha1-adrenoceptor-Gq signaling
      is upregulated in the failing myocardium to increase the myofibrillar Ca2+
      sensitivity mainly through the RhoA-Rho kinase pathway rather than through the
      protein kinase C pathway.

PMID- 11454568
TI  - Effect of a selective aldosterone receptor antagonist in myocardial infarction.
AB  - Myocardial infarction (MI) initiates adaptive tissue remodeling, which is
      essential for heart function (such as infarct healing) but is also important for
      maladaptive remodeling (for example, reactive fibrosis and left ventricular
      dilation). The effect of aldosterone receptor antagonism on these processes was
      evaluated in Sprague-Dawley rats using eplerenone, a selective aldosterone
      receptor antagonist. Infarct healing and left ventricular remodeling were
      evaluated at 3, 7, and 28 days after MI by determination of the diastolic
      pressure-volume relationship of the left ventricle, the infarct-thinning ratio,
      and the collagen-volume fraction. Eplerenone did not affect reparative collagen
      deposition as was evidenced by a similar collagen volume fraction in the
      infarcted myocardium between eplerenone and vehicle-treated groups at 7 and 28
      days post-MI. In addition, the thinning ratio, which is an index of infarct
      expansion, was comparable between the eplerenone and vehicle-treated animals at 7
      and 28 days post-MI. A protective effect of eplerenone was demonstrated at 28
      days post-MI, where reactive fibrosis in the viable myocardium was reduced in
      eplerenone-treated animals compared with vehicle-treated animals. Thus
      aldosterone receptor antagonism does not retard infarct healing but rather
      protects against maladaptive responses after MI.

PMID- 11454569
TI  - Fluvastatin inhibits O2- and ICAM-1 levels in a rat model with aortic remodeling
      induced by pressure overload.
AB  - Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is
      suggested to play an important role in the pathogenesis of vascular remodeling.
      The aim of the present study was to investigate the effects of the 3-hydroxy-3
      methylglutaryl (HMG) CoA reductase inhibitor fluvastatin on superoxide anion (O2
      ) production and ICAM-1 expression in a rat model with vascular remodeling
      induced by pressure overload. Two weeks after aortic banding, marked increases in
      O2- production and ICAM-1 protein levels were observed in the aorta. O2-
      formation and ICAM-1 immunoreactivity were mainly increased in the endothelium
      and adventitia of the aorta in banded rats. Oral administration of fluvastatin
      prevented both these changes and the development of perivascular fibrosis and
      increased the expression of endothelial nitric oxide synthase. Cholesterol and
      lipid peroxide levels in serum did not change in the banded rats. Thus the
      beneficial effects of fluvastatin seen in this study as well as its cholesterol
      lowering effect may contribute to attenuate the atherosclerotic process.

PMID- 11454570
TI  - Endotoxin stimulated cytokine production in rat vascular smooth muscle cells.
AB  - Because inflammatory processes may promote the development of atherosclerosis, we
      examined the activation of cytokine genes in rat vascular smooth muscle cells in
      vitro after treatment with bacterial lipopolysaccharide (LPS). Interleukin-1 (IL
      1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) mRNA increased in response
      to LPS. Activation of nuclear factor-kappaB (NF-kappaB) presumably results in NF
      kappaB binding to regulatory regions of target genes and activating
      transcription. We therefore compared the kinetics of NF-kappaB activation,
      cytokine message production, and TNF-alpha secretion. Maximum active NF-kappaB
      was found at 30 min after the addition of LPS and decreased thereafter. Increased
      IL-6 mRNA was detected at 30 min, increased TNF-alpha mRNA at 60 min, and
      increased IL-1 mRNA at 120 min. Secretion of TNF-alpha was dependent on LPS
      concentration and was first detected 120 min after LPS addition. Aspirin, which
      has been shown to inhibit NF-kappaB activation and cytokine secretion in other
      cell types, did not inhibit NF-kappaB activation or TNF-alpha secretion. However,
      aspirin reduced the amount of both TNF-alpha and IL-6 mRNA present 30 min after
      LPS addition by half (P < 0.05).

PMID- 11454571
TI  - Effects of kappa-opioid receptor activation on myocardium.
AB  - Kappa-opioid receptor stimulation of the heart transiently increases twitch
      amplitude and decreases Ca2+-dependent actomyosin Mg2+-ATPase activity through an
      undetermined mechanism. One purpose of the present study was to determine if the
      increase in twitch amplitude is due to changes in myofilament Ca2+ sensitivity.
      We also wanted to determine if kappa-opioid receptor activation alters maximum
      actin-myosin ATPase activity and Ca2+ sensitivity of tension in a way consistent
      with protein kinase A or protein kinase C (PKC) action. Rat hearts were treated
      with U50,488H (a kappa-opioid receptor agonist), phenylephrine plus propranolol
      (alpha-adrenergic receptor stimulation), isoproterenol (a beta-adrenergic
      receptor agonist), or phorbol 12-myristate 13-acetate (PMA, receptor independent
      activator of PKC) or were untreated (control), and myofibrils were isolated.
      U50,488H, phenylephrine plus propranolol, and PMA all decreased maximum Ca2+
      dependent actomyosin Mg2+-ATPase activity, whereas isoproterenol treatment
      increased maximum Ca2+-dependent actomyosin Mg2+- ATPase activity. Untreated
      myofibrils exposed to exogenous PKC-epsilon, but not PKC-delta, decreased maximum
      actomyosin Mg2+-ATPase activity. Langendorff-perfused hearts treated with
      U50,488H, phenylephrine plus propranolol, or isoproterenol had significantly
      higher ventricular ATP levels compared with control hearts. PKC inhibitors
      abolished the effects of U50,488H on Ca2+-dependent actomyosin Mg2+-ATPase
      activity and myocardial ATP levels. U50,488H and PMA treatment of isolated
      ventricular myocytes increased Ca2+ sensitivity of isometric tension compared
      with control myocytes at pH 7.0. The U50,488H-dependent increase in Ca2+
      sensitivity of tension was retained at pH 6.6. Together, these findings are
      consistent with the hypotheses that 1) the positive inotropy associated with
      kappa-opioid receptor activation may be due in part to a PKC-mediated increase in
      myofilament Ca2+-sensitivity of tension and 2) the kappa-opioid receptor-PKC
      pathway is a modulator of myocardial energy status through reduction of
      actomyosin ATP consumption.

PMID- 11454572
TI  - Glutathione supplementation and training increases myocardial resistance to
      ischemia-reperfusion in vivo.
AB  - The present study examined the effects of oral reduced glutathione (GSH)
      supplementation in conjunction with endurance training on contractile function,
      antioxidant defense, and oxidative damage in response to ischemia-reperfusion
      (I/R) in rat hearts. Female Sprague-Dawley rats (age 4 mo, n = 72) were randomly
      assigned to a treadmill-trained (T; 25 m/min, 15% grade, for 75 min/day, 5
      days/wk, for 10 wk) or untrained (U) group. Each group was further divided into
      rats receiving 5 g GSH/kg diet during the final 17 days of training (GSH-S) and
      control (C) groups. One-half of each group of rats was subjected to I/R by
      surgical occlusion of the main coronary artery for 45 min, followed by 30-min
      reperfusion or sham operation. Left ventriclar (LV) peak systolic pressure (LVSP)
      and contractility (+dP/dt), measured with a catheter inserted into the LV via the
      carotid artery, decreased with I/R in all groups (P < 0.05). However, LVSP with
      I/R in the T/GSH-S group was 9.5%, 17%, and 18% higher (P < 0.05) than that in
      the U/GSH-S, T/C, and U/C groups, respectively. +dP/dt with I/R was 19%, 27%, and
      29% (P < 0.05) greater in the T/GSH-S group versus the T/C, U/GSH-S, and U/C
      groups, respectively. I/R decreased heart GSH content by 12-17% (P < 0.05) and
      increased oxidized glutathione (GSSG) by 20-27% (P < 0.05). T/GSH-S hearts showed
      15% higher GSH (P < 0.05) and a 32% higher GSH-to-GSSG ratio (P < 0.05) than the
      U/C group at the end of I/R. Myocardial superoxide dismutase, GSH peroxidase,
      glutathione reductase, and gamma-glutamyl transpeptidase activities were
      increased with treadmill training in both GSH-S and C rats. I/R induced
      myocardial lipid peroxidation and lactate dehydrogenase release were attenuated
      with T/GSH-S treatment. The present data indicate that training in conjunction
      with dietary GSH supplementation can increase myocardial GSH content and
      antioxidant defense capacity, thereby protecting the intact heart against
      oxidative damage and functional retardation caused by I/R.

PMID- 11454573
TI  - Larger late sodium conductance in M cells contributes to electrical heterogeneity
      in canine ventricle.
AB  - Action potentials and whole cell sodium current were recorded in canine
      epicardial, midmyocardial, and endocardial myocytes in normal sodium at 37
      degrees C. Tetrodotoxin (TTX) reduced the action potential duration of
      midmyocardial cells to a greater degree than either epicardial or endocardial
      cells. Whole cell recordings in potassium-free and very-low-chloride solutions
      revealed a slowly decaying current that was completely inhibited by 5 microM TTX
      or replacement of external and internal sodium with the impermeant cation N
      methyl-D-glucamine. Late sodium current density at 0 mV was 47% greater in
      midmyocardial cells and averaged -0.532 +/- 0.058 pA/pF in endocardial, -0.463 +/
      0.068 pA/pF in epicardial, and -0.785 +/- 0.070 pA/pF in midmyocardial cells.
      Neither the frequency dependence of late sodium current nor its recovery from
      inactivation exhibited transmural differences. After a 4.5-s pulse to -30 mV,
      late sodium current recovered with a single time constant of 140 ms. We conclude
      that a larger late sodium conductance in midmyocardial cells will favor longer
      action potentials in these cells. More importantly, drugs that slow inactivation
      of sodium channels will produce a nonuniform response across the ventricular wall
      that is proarrhythmic.

PMID- 11454574
TI  - Quantification of 3-D regional myocardial deformation: shape-based analysis of
      magnetic resonance images.
AB  - A comprehensive three-dimensional (3-D) shape-based approach for quantification
      of regional myocardial deformations was evaluated in a canine model (n = 8 dogs)
      with the use of cine magnetic resonance imaging. The shape of the endocardial and
      epicardial surfaces was used to track the 3-D trajectories of a dense field of
      points over the cardiac cycle. The shape-based surface displacements are
      integrated with a continuum biomechanics model incorporating myofiber
      architecture to estimate both cardiac- and fiber-specific endocardial and
      epicardial strains and shears for 24 left ventricular regions. Whereas radial and
      circumferential end-systolic strains were fairly uniform, there was a significant
      apex-to-base gradient in longitudinal strain and radial-longitudinal shear. We
      also observed transmural epicardial-to-endocardial gradients in both cardiac- and
      fiber-specific strains. The increase in endocardial strain was accompanied by
      increases in radial-longitudinal shear and radial-fiber shears in the
      endocardium, supporting previous theories of regional myocardial deformation that
      predict considerable sliding between myocardial fibers.

PMID- 11454575
TI  - Quantitative analysis of intratumoral infusion of color molecules.
AB  - Intratumoral infusion has a potential for improving distribution of drugs. To
      optimize the infusion, we developed a novel technique to quantify the
      distribution volume of color molecules (Vd) in solid tumors. Evans blue-labeled
      albumin was infused locally with the use of a needle into a rat fibrosarcoma ex
      vivo under different pressures. After the infusion, tumor tissues were sectioned
      serially into thin slices. The blue area in each slice was quantified with the
      use of the newly developed technique. The Vd was calculated based on the blue
      area and the slice thickness. Our data showed that infusion pressure and volume
      (V(i)) had significant effects on Vd. The median of Vd/V(i) decreased from 2.99
      to 1.79 when infusion pressure was increased from 50 to 163 cmH2O, presumably due
      to retardation of convective transport. In addition, the coefficient of variation
      in Vd/V(i) was increased from 0.13 at 50 cmH2O to 0.64 at 163 cmH2O. The
      dependence of Vd/V(i) and its variation on infusion pressure suggests that 1)
      infusion-induced tissue deformation is unpredictable and 2) both the
      unpredictability and the interstitial retardation of convective transport
      increase with infusion pressure.

PMID- 11454576
TI  - Calcium-mediated activation of pyruvate dehydrogenase in severely injured
      postischemic myocardium.
AB  - Indirect evidence suggests that activity of pyruvate dehydrogenase (PDH)
      influences recovery of the myocardium after transient ischemia. The present study
      examined the relationship between postischemic injury and activity of PDH and the
      role of mitochondrial calcium uptake for observed changes in PDH activity.
      Isovolumically beating isolated rat hearts perfused with erythrocyte-enriched
      buffer containing glucose, palmitate, and insulin were submitted to either 20 or
      35 min of no-flow ischemia. After 20 min of no-flow ischemia, hearts exhibited
      complete recovery of developed left ventricular pressure (DLVP). The proportion
      of myocardial PDH in the active state was modestly increased to 38% (compared
      with 13% in control hearts) without a change in glucose oxidation. In contrast,
      in hearts subjected to 35 min of no-flow ischemia (which exhibited poor recovery
      of DLVP), there was marked stimulation of glucose oxidation (+460%; P < 0.01) and
      pronounced increase in the active fraction of PDH to 72% (P < 0.01). Glycolytic
      flux was not significantly altered. Ruthenium red (6 microM) completely abolished
      the activation of PDH and the increase in glucose oxidation. The results indicate
      that variable stimulation of glucose oxidation during reperfusion is related to
      different degrees of activation of PDH, which depends on the severity of the
      ischemic injury. Activation of PDH seems to be mediated by myocardial calcium
      uptake.

PMID- 11454577
TI  - Decrease in coronary vascular volume in systole augments cardiac contraction.
AB  - Coronary arterial inflow is impeded and venous outflow is increased as a result
      of the decrease in coronary vascular volume due to cardiac contraction. We
      evaluated whether cardiac contraction is influenced by interfering with the
      changes of the coronary vascular volume over the heart cycle. Length-tension
      relationships were determined in Tyrode-perfused rat papillary muscle and when
      coronary vascular volume changes were partly inhibited by filling it with
      congealed gelatin or perfusing it with a high viscosity dextran buffer. Also,
      myocyte thickening during contraction was reduced by placing a silicon tube
      around the muscle. Increasing perfusion pressure from 8 to 80 cmH2O, increased
      developed tension by approximately 40%. When compared with the low perfusion
      state, developed tension of the gelatin-filled vasculature was reduced to 43 +/-
      6% at the muscle length where the muscle generates the largest developed tension
      (n = 5, means +/- SE). Dextran reduced developed tension to 73 +/- 6% (n = 6).
      The silicon tube, in low perfusion state, reduced the developed tension to 83 +/-
      7% (n = 4) of control. Time-control and oxygen-lowering experiments show that the
      findings are based on mechanical effects. Thus interventions to prevent myocyte
      thickening reduce developed tension. We hypothesize that when myocyte thickening
      is prevented, intracellular pressure increases and counteracts the force produced
      by the contractile apparatus. We conclude that emptying of the coronary
      vasculature serves a physiological purpose by facilitating cardiomyocyte
      thickening thereby augmenting force development.

PMID- 11454578
TI  - Selective blockade of mitochondrial K(ATP) channels does not impair myocardial
      oxygen consumption.
AB  - Opening of mitochondrial ATP-sensitive potassium (K(ATP)) channels has been
      postulated to prevent inhibition of respiration resulting from matrix contraction
      during high rates of ATP synthesis. Glibenclamide, which blocks K(ATP) channels
      on the sarcolemma of vascular smooth muscle cells and myocardial myocytes as well
      as on the inner mitochondrial membrane, results in a decrease of myocardial
      oxygen consumption (MVO2) both at rest and during exercise. This study examined
      whether this represents a primary effect of blockade of mitochondrial K(ATP)
      channels or occurs secondary to coronary resistance vessel constriction with a
      decrease of coronary blood flow (CBF) and myocardial oxygen availability. MVO2
      was measured at rest and during treadmill exercise in 10 dogs during control
      conditions, after selective mitochondrial K(ATP) channel blockade with 5
      hydroxydecanoate (5-HD), and after nonselective K(ATP) channel blockade with
      glibenclamide. During control conditions, exercise resulted in progressive
      increases of CBF and MVO2. Glibenclamide (50 microg x kg(-1) x min(-1) ic)
      resulted in a 17 +/- 6% decrease of resting CBF with a downward shift of CBF
      during exercise and a decrease of coronary venous PO2, indicating increased
      myocardial oxygen extraction. In contrast with the effects of glibenclamide, 5-HD
      (0.7 mg x kg(-1) x min(-1) ic) had no effect on CBF, MVO2, or myocardial oxygen
      extraction. These findings suggest that glibenclamide decreased MVO2 by causing
      resistance vessel constriction with a decrease of CBF and oxygen available to the
      myocardium rather than to a primary reduction of mitochondrial respiration.

PMID- 11454579
TI  - Alterations of Ca2+ mobilizing properties in migrating endothelial cells.
AB  - Endothelial migration is one of the major events of pathological
      neovascularization. We compared the characteristics of Ca2+ mobilization in
      nonconfluent, confluent, and migrating endothelial cells. Migration of
      endothelial cells was induced by wounding the confluent cell monolayer. The basal
      intracellular Ca2+ concentration was lower in migrating cells and higher in
      confluent cells than in nonconfluent cells. Thapsigargin (TG)-induced Ca2+ leak
      and TG-evoked Ca2+ entry were accelerated in migrating cells, whereas the latter
      was suppressed in confluent cells. The ATP-induced Ca2+ transient was also much
      larger in migrating cells than in confluent cells. These alterations were also
      observed in a cell as an intracellular polarization, i.e., the leading edge
      showed an acceleration of TG-evoked Ca2+ entry and an augmentation of the ATP
      induced Ca2+ transient. Endothelial migration was significantly suppressed by TG
      or cyclopiazonic acid. These observations suggest that the alterations of Ca2+
      store site-related Ca2+ mobilizations, i.e., Ca2+ sequestration, release, and TG
      evoked Ca2+ entry, may be involved in the cellular mechanisms of endothelial
      migration.

PMID- 11454580
TI  - Hypertonic saline method accurately determines parallel conductance for dual
      field conductance catheter.
AB  - Conversion of conductance catheter data to absolute ventricular volumes requires
      assessment of parallel conductance (G(P)). We determined the accuracy of GP
      obtained by the hypertonic saline method (G(P)saline) compared with
      angiographically derived GP (G(P)Angio) and quantified the variabilities of GP
      for the dual-field conductance catheter method in nine anesthetized sheep studied
      at baseline, treated with dobutamine, and subjected to volume loading and beta
      blockade. G(P)saline and G(P)Angio showed an excellent linear correlation
      (G(P)saline = 1.002 x G(P)Angio + 0.001 Omega(-1), R2 = 0.92), and Bland-Altman
      analysis yielded a nonsignificant bias and narrow limits of agreement (bias +/-
      2SD = 0.002 +/- 0.112 Omega(-1)). Within-animal variability of GP was very
      similar with both methods and was due to changes in blood conductivity rather
      than geometrical changes. Variability between animals was significant (26.3% of
      mean for G(P)saline and 25.7% for G(P)Angio) and thus warrants individual
      assessment. Variations during the cardiac cycle were not significantly different
      from zero. With biplane angiography used as gold standard, the hypertonic saline
      method accurately determines GP for the dual-field conductance catheter over a
      wide range of hemodynamic conditions.

PMID- 11454581
TI  - Characterization of effects of endothelin-1 on the L-type Ca2+ current in human
      atrial myocytes.
AB  - The effects of endothelin-1 (ET-1) on the L-type Ca2+ current (I(Ca)) were
      examined in whole cell patch-clamped human atrial myocytes. Depending on the
      initial current density, ET-1 (10 nM) increased the amplitude of I(Ca) by 99 +/-
      7% or decreased it by 33 +/- 2%. The stimulatory effect predominated on current
      of low density (2.3 +/- 0.2 pA/pF), whereas I(Ca) of higher density (5.8 +/- 0.3
      pA/pF) was inhibited by ET-1. After I(Ca) stimulation by 1 microM isoproterenol,
      ET-1 always inhibited the current by 32 +/- 7% (P < 0.05), an effect that was
      suppressed by pretreating myocytes with pertussis toxin. Atrial natriuretic
      peptide (ANP) inhibited I(Ca) (41 +/- 3%) by reducing intracellular cAMP
      concentration. In ANP-treated myocytes, the stimulatory effect of ET-1 on I(Ca)
      predominated (52 +/- 7%). The inhibitory effect of ET-1 on I(Ca) was blocked by
      the ET(A) antagonist BQ-123, whereas the stimulatory effect was suppressed by the
      ET(B) agonist BQ-788. We conclude that ET-1 has opposite effects on I(Ca)
      depending on the baseline amplitude of current, and both subtype ET receptors are
      implicated in the signal transduction pathways.

PMID- 11454582
TI  - Differences in the dynamic cerebrovascular response between stepwise up tilt and
      down tilt in humans.
AB  - We studied dynamic cerebrovascular responses in eight healthy humans during
      repetitive stepwise upward tilt (SUT) and stepwise downward tilt (SDT) maneuvers
      between supine and 70 degrees standing at intervals of 60 s. Mean cerebral blood
      flow velocity (FV(MCA)) was measured at the middle cerebral artery (MCA) with
      transcranial Doppler ultrasonography. Mean arterial blood pressure (ABP) was
      measured via the radial artery and adjusted at the level of the MCA (ABP(MCA)).
      Cerebral critical closing pressure (P(CC)) was estimated from the systolic
      diastolic relationship between FV(MCA) and ABP(MCA). ABP(MCA) minus P(CC) was
      considered the cerebral perfusion pressure (CPP). The tilt maneuvers produced
      stepwise changes in both CPP and FV(MCA). The FV(MCA) response to SUT was well
      characterized by a linear second-order model. However, that to SDT presented a
      biphasic behavior that was described significantly better (P < 0.05) by the
      addition of a slowly responding component to the second-order model. This
      difference may reflect both different cardiovascular responses to SUT or SDT and
      different cerebrovascular autoregulatory behaviors in response to decreases or
      increases in CPP.

PMID- 11454583
TI  - Selective recruitment of neutrophils and lymphocytes by thrombin: a role for NF
      kappaB.
AB  - With the use of a whole blood laminar flow chamber system, we examined the types
      of leukocytes, adhesion molecules and the role of nuclear factor-kappaB (NF
      kappaB) in thrombin-induced leukocyte recruitment. Primary human umbilical vein
      endothelial cells (HUVEC) stimulated with thrombin induced a significant increase
      in P-selectin-dependent neutrophil recruitment. Unexpectedly, brief thrombin
      stimulation (3 min) of endothelium also induced a significant lymphocyte
      recruitment 4 h later in addition to neutrophil recruitment. E-selectin antibody
      reduced neutrophil recruitment by >90%, whereas vascular adhesion molecule-1
      (VCAM-1)/alpha4-integrin were primarily responsible for lymphocyte recruitment.
      To examine whether NF-kappaB contributed to leukocyte recruitment 4 h post
      thrombin stimulation, we treated HUVEC with the NF-kappaB inhibitor MG-132 for 1
      h before thrombin stimulation. MG-132 significantly reduced the number of rolling
      (77.1%) and adherent (79.9%) leukocytes compared with thrombin stimulation alone.
      The inhibitor was more effective at preventing lymphocyte than neutrophil
      recruitment, consistent with its greater effect on VCAM-1 versus E-selectin
      expression. Tumor necrosis factor-alpha- and MG-132-treated HUVEC displayed no
      inhibition of leukocyte recruitment despite a decrease in NF-kappaB activation.
      In summary, thrombin causes predominant neutrophil recruitment via rapid P
      selectin expression but also a delayed E-selectin- and VCAM-1-dependent
      neutrophil and lymphocyte recruitment via de novo protein synthesis. Although NF
      kappaB mobilization was essential for thrombin-mediated VCAM-1-dependent
      recruitment, it only partially contributed to E-selectin-dependent recruitment.

PMID- 11454584
TI  - Nitric oxide limits coronary vasoconstriction by a shear stress-dependent
      mechanism.
AB  - Increases in shear stress promote coronary vasodilation by stimulating the
      production of nitric oxide (NO). Whether shear stress-induced NO production also
      limits vasoconstriction in the coronary microcirculation in vivo is unknown.
      Accordingly, we measured microvascular diameter and flow velocity in the beating
      heart along with estimated blood viscosity to calculate shear stress during
      vasoconstriction with endothelin or vasopressin. Measurements were repeated in
      the presence of NG-monomethyl-L-arginine (L-NMMA) to inhibit NO production and BQ
      788 to block NO-linked endothelin type B receptors. BQ-788 did not augment steady
      state constriction to endothelin, suggesting that NO production via activation of
      this receptor is inconsequential. L-NMMA potentiated constriction to both
      agonists, particularly in small arteries (inner diameter >120 microm). Shear
      stresses in small arteries were elevated during constriction and further elevated
      during constriction after L-NMMA. These observations suggest that NO production
      limits vasoconstriction in the coronary microcirculation and that the principal
      stimulus for this governance is elevated shear stress. The degree of shear stress
      moderation of constriction is heterogeneously distributed, with small arteries
      displaying a higher degree of shear stress regulation than arterioles. These
      results provide the strongest evidence to date that shear stress-mediated
      production of NO exerts a "braking" influence on constriction in the coronary
      microcirculation.

PMID- 11454585
TI  - Mechanism of uterine vascular refractoriness to endothelin-1 in pregnant sheep.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor and produces marked pressor
      responses when given systemically. Studies in sheep have demonstrated that during
      pregnancy the uterine vasculature is refractory to exogenously administered ET-1.
      We hypothesize that this pregnancy-dependent refractoriness is due to an
      upregulation of local uterine metabolism of ET-1 and/or ET(B) receptors and/or
      downregulation of local uterine ET(A) receptors. To investigate these
      possibilities, 21 nonpregnant and 17 pregnant sheep were used. Dose-response
      curves to intravenous infusion of ET-1 and phenylephrine were generated for
      pregnant and nonpregnant sheep. ET-1 infused systemically demonstrated
      vasoconstriction in the systemic and renal vasculature of pregnant and
      nonpregnant animals and vasoconstriction in the uterine vasculature of
      nonpregnant animals. The pregnant animals showed no uterine vascular response to
      ET-1. In contrast, phenylephrine showed vasoconstriction in the systemic, renal,
      and uterine circulations in both pregnant and nonpregnant sheep. After
      experimentation, the animals were euthanized, and tissues were harvested for
      Western blot and activity analysis of neutral endopeptidase (NEP) or RT-PCR
      analysis of endothelin-converting enzyme (ECE) and ET(A) and ET(B) receptors. The
      content and activity of NEP in the uterine and renal vasculature of pregnant and
      nonpregnant animals were similar. RT-PCR demonstrated the presence of ECE in the
      uterine vasculature of pregnant and nonpregnant sheep. ET(A) receptor mRNA was
      significantly reduced in pregnant compared with nonpregnant sheep, whereas ET(B)
      receptor mRNA remained unchanged. We conclude that the uterine vascular
      refractoriness seen in the pregnant sheep is due to a downregulation of ET(A)
      receptors.

PMID- 11454586
TI  - Angiotensin II modulates catecholamine release into interstitial fluid of canine
      myocardium in vivo.
AB  - This study tested the hypothesis that exogenous infusion of angiotensin II (ANG
      II) leads to the release of catecholamines [norepinephrine (NE) and epinephrine
      (EPI)] into the cardiac interstitial fluid (ISF) space of dogs with adrenals
      intact (AI) (n = 7) and with adrenals clamped (AC) (n = 5). LV ISF samples were
      collected at 3-min intervals during administration of ANG II (100 microM ANG II
      at 1 ml/min for 10 min) to right atrial neurons via their local arterial blood
      supply and during electrical stimulation of the stellate ganglia of open-chest
      anesthetized dogs. In AI dogs, ANG II caused ISF NE to increase fivefold (P <
      0.05) without a significant increase in coronary sinus (CS) NE. Electrical
      stimulation (5 ms, 4 Hz, 8-14 V, and 10 min) of the stellate ganglia caused a
      similar increase in ISF NE (P < 0.05), accompanied by a sevenfold increase in CS
      NE (P < 0.05). ISF EPI increased greater than sixfold during ANG II infusion (P <
      0.05) and during stellate stimulation. However, during ANG II infusions, aorta
      plasma EPI levels increased fourfold in AI dogs, whereas in AC dogs, CS NE and
      EPI levels were unaffected during ANG II infusions. Nevertheless, baseline ISF NE
      and EPI did not differ and increased to a similar extent during ANG II infusions
      in AI versus AC dogs. Thus exogenously administered ANG II increases the amount
      of NE liberated into the ISF independent of the adrenal contribution, the amount
      matching that induced by electrical stimulation of all cardiac sympathetic
      efferent neurons. In contrast, NE spillover into the CS occurred only during
      electrical stimulation of stellate ganglia. NE release and uptake mechanisms
      within the myocardium are differently affected, depending on how the final common
      pathway of the sympathetic efferent nervous system is modified.

PMID- 11454587
TI  - Right ventricular oxygen supply/demand balance in exercising dogs.
AB  - This is the first investigation of right ventricular (RV) myocardial oxygen
      supply/demand balance in a conscious animal. A novel technique developed in our
      laboratory was used to collect right coronary (RC) venous blood samples from
      seven instrumented, conscious dogs at rest and during graded treadmill exercise.
      Contributions of the RV oxygen extraction reserve and the RC flow reserve to
      exercise-induced increases in RV oxygen demand were measured. Strenuous exercise
      caused a 269% increase in RV oxygen consumption. Expanded arteriovenous oxygen
      content difference (A-V(Delta)O2) provided 58% of this increase in oxygen demand,
      and increased RC blood flow (RCBF) provided 42%. At less strenuous exercise,
      expanded A-V(Delta)O2 provided 60-80% of the required oxygen, and increases in
      RCBF were small and driven by increased aortic pressure. RC resistance fell only
      at strenuous exercise after the extraction reserve had been mobilized. Thus RC
      resistance was unaffected by large decreases in RC venous PO2 until an apparent
      threshold at 20 mmHg was reached. Comparisons of RV findings with published left
      ventricular data from exercising dogs demonstrated that increased O2 demand of
      the left ventricle is met primarily by increasing coronary flow, whereas
      increased O2 extraction makes a greater contribution to RV O2 supply.

PMID- 11454588
TI  - Endogenous nitric oxide modulates myocardial oxygen consumption in canine right
      ventricle.
AB  - The role of endogenous nitric oxide (NO) in modulating myocardial oxygen
      consumption (MVO2) is unclear, in part because of systemic and coronary
      hemodynamic effects of blocking NO release. This study evaluated the effect of NO
      on right ventricular MVO2 under controlled hemodynamic conditions. In 12 open
      chest dogs, N(omega)-nitro-L-arginine methyl ester (L-NAME, 150 microg/min), a NO
      synthase (NOS) blocker, was infused into the right coronary artery. Heart rate
      and mean aortic pressure were constant. Right coronary blood flow and right
      ventricular MVO2 were measured at normal and elevated right coronary perfusion
      pressures (RCP) before and after L-NAME. To avoid effects of NO synthesis
      blockade on right coronary blood flow, which might have altered right ventricular
      MVO2, experiments, were conducted during adenosine-induced maximal coronary
      vasodilation. L-NAME did not affect right coronary blood flow (P = 0.51).
      However, L-NAME significantly increased right ventricular MVO2 (6% at RCP 100
      mmHg, and 21% at RCP 180 mmHg). Right coronary blood flow varied with perfusion
      pressure (P < 0.02), and the elevation of MVO2 produced by L-NAME increased at
      higher flows (P < 0.04), consistent with the greater shear stress-mediated
      release of NO. These findings indicate that endogenous NO limits right
      ventricular MVO2.

PMID- 11454589
TI  - Endogenous nitric oxide enhances coupling between O2 consumption and ATP
      synthesis in guinea pig hearts.
AB  - Endogenous nitric oxide (eNO) modulates tissue respiration. To test whether eNO
      modulates myocardial O2 consumption (MVO2), ATP synthesis, and metabolic
      efficiency, we used isolated isovolumic guinea pig hearts perfused at a constant
      flow. N(omega)-nitro-L-arginine (L-NNA; 5 x 10(-5) mol/l) was used to inhibit eNO
      production. MVO2 was measured at different levels of cardiac work, estimated as
      the rate-pressure product (RPP). ATP content and synthesis rate were determined
      using (31)P NMR and magnetization transfer during high cardiac work. L-NNA
      increased coronary vascular resistance (19 +/- 3%, P < 0.05) and MVO2 (12 +/- 3%,
      P < 0.05) without an increase in the RPP. In contrast, vehicle infusion resulted
      in insignificant changes in coronary vascular resistance (3 +/- 2%, P > 0.05) and
      MVO2 (-2 +/- 1%, P > 0.05). Compared with vehicle, L-NNA caused a higher MVO2
      both during KCl arrest (L-NNA 5.6 +/- 0.5 vs. vehicle 3.0 +/- 0.4 micromol x min(
      1) x mg x dry wt(-1), P < 0.05) and during increased cardiac work elicited by
      elevating perfusate Ca2+, indicating an upward shift in the relationship between
      contractile performance (measured as RPP) and MVO2. However, neither ATP contents
      nor ATP synthesis rates were different in the two groups during high cardiac
      work. Thus, because inhibition of eNO production by L-NNA increased MVO2 without
      a change in the ATP synthesis rate, these data suggest that eNO increases
      myocardial metabolic efficiency by reducing MVO2 in the heart.

PMID- 11454590
TI  - Adenosine A3 agonist cardioprotection in isolated rat and rabbit hearts is
      blocked by the A1 antagonist DPCPX.
AB  - Adenosine A3 agonists have been shown to protect ischemic rat and rabbit
      myocardium. However, these agonists have been reported to exert A3 independent
      effects, and no cardiac A3 receptor has yet been identified. We thus tested
      whether A3 agonist protection is due to A1 receptor activation. Isolated rat and
      rabbit hearts were subjected to 25 and 45 min of global ischemia, respectively.
      Rat hearts pretreated with adenosine (100 microM), the A3 agonist 2-chloro-N6-(3
      iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA, 50 nM), and vehicle
      recovered 73 +/- 2%, 75 +/- 4%, and 46 +/- 4%, respectively, of preischemic left
      ventricular developed pressure (LVDP) after 30 min of reperfusion. The A1
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM) blocked the
      beneficial effects of Cl-IB-MECA (51 +/- 5%) and adenosine (47 +/- 6%). In rabbit
      hearts, the beneficial effects of the A3 agonist N6-(3-iodobenzyl)-adenosine-5'-N
      methyluronamide (50 nM) and the A1 agonist 2-chloro-N6-cyclopentyladenosine (100
      nM) on postischemic LVDP (75 +/- 4 and 74 +/- 5%, respectively) were blocked by
      DPCPX (34 +/- 4 and 36 +/- 3%, respectively). The reduction in infarct size with
      both agonists was also completely blocked by DPCPX. These results suggest that
      these A3 agonists protect ischemic myocardium via A1 receptor activation.

PMID- 11454591
TI  - Pyruvate improves cerebral metabolism during hemorrhagic shock.
AB  - Pyruvate (PYR) improves cellular and organ function hypoxia and ischemia by
      stabilizing the reduced nicotinamide adenine dinucleotide redox state and
      cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the
      effects of intravenous pyruvate on neocortical function, indexes of the cytosolic
      redox state, cellular energy state, and ischemia during a prolonged (4 h)
      controlled arterial hemorrhage (40 mmHg) in swine. Thirty minutes after the onset
      of hemorrhagic shock, sodium PYR (n = 8) was infused (0.5 g x kg(-1) x h(-1)) to
      attain arterial levels of 5 mM. The volume and osmotic effects were matched with
      10% NaCl [hypertonic saline (HTS)] (n = 8) or 0.9% NaCl [normal saline (NS)] (n =
      8). During the hemorrhage protocol, the time to peak hemorrhage volume was
      significantly delayed in the PYR group compared with the HTS and NS groups (94 +/
      5 vs. 73 +/- 6 and 72 +/- 4 min, P < 0.05). In addition to the early onset of
      the decompensatory phase of hemorrhagic shock, the complete return of the
      hemorrhage volume during decompensatory shock resulted in the death of five and
      four animals, respectively, in the HTS and NS groups. In contrast, in the PYR
      group, reinfusion of the hemorrhage volume was slower and all animals survived
      the 4-h hemorrhage protocol. During hemorrhage, the PYR group also exhibited
      improved cerebral cortical metabolic and function status. PYR slowed and reduced
      the rise in neocortical microdialysis levels of adenosine, inosine, and
      hypoxanthine and delayed the loss of cerebral cortical biopsy ATP and
      phosphocreatine content. This improvement in energetic status was evident in the
      improved preservation of the electrocorticogram in the PYR group. PYR also
      prevented the eightfold increase in the excitotoxic amino acid glutamate observed
      in the HTS group. The findings show that PYR administered after the onset of
      hemorrhagic shock markedly improves cerebral metabolic and functional status for
      at least 4 h.

PMID- 11454592
TI  - Complex AV nodal dynamics during ventricular-triggered atrial pacing in humans.
AB  - In vitro experiments have shown that the complexity of atrioventricular nodal
      (AVN) conduction dynamics increases with heart rate. Although complex AVN
      dynamics (e.g., alternans) have been observed clinically, human AVN dynamics
      during rapid pacing have not been systematically investigated. We studied such
      dynamics during ventricular-triggered atrial pacing in 37 patients with normal
      AVN function (18 patients with dual AVN pathway physiology and 19 patients
      without). Alternans, which always resulted from single pathway conduction,
      occurred in 18 patients. In 16 patients (3 of whom also had alternans),
      quasisinusoidal AVN conduction oscillations occurred (mean frequency 0.02 Hz);
      such oscillations have not been previously reported. There were no significant
      differences in the dynamics for patients with or without dual AVN pathways. To
      illuminate the governing dynamic mechanism, a second atrial pacing trial was
      performed on 12 patients after autonomic blockade. Blockade facilitated alternans
      but inhibited oscillations. This study suggests that rapid AVN excitation in vivo
      can lead to autonomically mediated AVN conduction oscillations or single pathway
      alternans that are a function of inherent nonlinear dynamic AVN tissue
      properties.

PMID- 11454593
TI  - Nitric oxide release during alpha1-adrenoceptor-mediated constriction of
      arterioles.
AB  - We examined endothelial modulation of norepinephrine (NE)-mediated constriction
      in isolated, cannulated, first-order arterioles from skeletal muscle of rats.
      Acute arteriolar constrictor responses to NE (10(-9) to 10(-7) M) were
      significantly (P < 0.05) enhanced after either endothelial denudation or
      inhibition of nitric oxide synthase with NG-monomethyl-L-arginine (10(-4) M, 30
      min). In contrast, arteriolar constrictions to NE were not different after
      treatment with either the cyclooxygenase inhibitor diclofenac (10(-6) M, 30 min)
      or the K+-channel blocker tetrabutylammonium (5 x 10(-5) M, 30 min). We also
      measured arteriolar responses to the vasoconstrictor PGF2alpha; responses were
      not altered by any of the experimental treatments, which indicates that this
      phenomenon is not ubiquitous to all vasoconstricting agents. Mechanistically, we
      examined vascular smooth muscle (VSM) and endothelial cell calcium. Both NE and
      PGF2alpha significantly increased VSM cell calcium measurements; however,
      endothelial cell calcium was significantly increased with NE or phenylephrine (an
      alpha1-adrenergic agonist) but not with PGF2alpha or UK-14304 (an alpha2
      adrenergic agonist). Together these findings suggest that in rat cremaster first
      order arterioles, NE stimulates an increase in VSM calcium via adrenergic
      receptors with subsequent increase in endothelial cell calcium, possibly via
      stimulation of alpha1-adrenergic receptors on the arteriolar endothelium. The
      burst in endothelial cell calcium may then lead to the production of nitric
      oxide, which diffuses to the VSM, attenuates constriction, and maintains at least
      some minimal level of blood flow.

PMID- 11454594
TI  - 31P NMR quantitation of phosphorus metabolites in rat heart and skeletal muscle
      in vivo.
AB  - The aim of this study was to examine two methods of 31P NMR quantitation of
      phosphocreatine (PCr), ATP, and P(i) in rat heart and skeletal muscle in vivo.
      The first method employed an external standard of phenylphosphonic acid (PPA; 10
      mM), and the second method used an enzymatic measurement of tissue ATP equated to
      the area under the betaATP peak. With the use of the external standard, the
      concentrations of ATP, PCr, and P(i) in the rat heart were 4.48 +/- 0.33, 9.21 +/
      0.65, and 2.25 +/- 0.16 micromol/g wet wt, respectively. With the use of the
      internal ATP standard, measured on the same tissue, the contents (means +/- SE)
      were 4.78 +/- 0.19, 9.83 +/- 0.18, and 2.51 +/- 0.33 micromol/g wet wt,
      respectively (n = 7). In skeletal muscle, ATP, PCr, and P(i) were 6.09 +/- 0.19,
      23.44 +/- 0.88, and 1.81 +/- 0.18 micromol/g wet wt using the PPA standard and
      6.03 +/- 0.19, 23.30 +/- 1.30, and 1.82 +/- 0.19 micromol/g wet wt using the
      internal ATP standard (n = 6). There was no significant difference for each
      metabolite as measured by the two methods of quantification in heart or skeletal
      muscle. The results validate the use of an external reference positioned
      symmetrically above the coil and imply that each has similar NMR sensitivities
      (similar signal amplitude per mole of 31P between PPA and tissue phosphorus
      compounds). We conclude that PCr, ATP, and P(i) are nearly 100% visible in the
      normoxic heart and nonworking skeletal muscle given the errors of measurement.

PMID- 11454595
TI  - Peroxisome proliferator-activated receptor-alpha ligands inhibit cardiac
      lipoprotein lipase activity.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors that regulate gene expression of lipoprotein lipase (LPL)
      in liver and adipose tissue. We examined the direct effect of PPAR-alpha ligands
      on LPL catalytic activity in cultured cardiomyocytes from adult rat heart. After
      overnight culture (16 h), 1 microM Wy-14643 and 10 microM BM-17.0744 decreased
      total cellular LPL activity to approximately 50% of control with no change in
      enzyme synthesis or mass; as a consequence, PPAR-alpha activation produced a
      significant decrease in LPL specific activity (mU/ng LPL protein). Wy-14643 and
      BM-17.0744 also reduced heparin-releasable LPL activity and mass in the culture
      medium. Inhibition of LPL activity by Wy-14643 did not reduce the ability of
      insulin plus dexamethasone to stimulate cellular and heparin-releasable LPL
      activities. A similar inhibitory effect on cellular and heparin-releasable LPL
      activity was observed when cardiomyocytes were cultured with 60 microM linoleic
      acid. In conclusion, two different PPAR-alpha ligands (Wy-14643 and BM-17.0744)
      inhibited cellular LPL activity in cultured cardiomyocytes by a
      posttranscriptional and posttranslational mechanism.

PMID- 11454596
TI  - Negative wave reflections in pulmonary arteries.
AB  - The pulmonary arterial branching pattern suggests that the early systolic forward
      going compression wave (FCW) might be reflected as a backward-going expansion
      wave (BEW). Accordingly, in 11 open-chest anesthetized dogs we measured proximal
      pulmonary arterial pressure and flow (velocity) and evaluated wave reflection
      using wave-intensity analysis under low-volume, high-volume, high-volume + 20
      cmH2O positive end-expiratory pressure (PEEP), and hypoxic conditions. We defined
      the reflection coefficient R as the ratio of the energy of the reflected wave
      (BEW [-]; backward-going compression wave, BCW [+]) to that of the incident wave
      (FCW [+]). We found that R = -0.07 +/- 0.02 under low-volume conditions, which
      increased in absolute magnitude to -0.20 +/- 0.04 (P < 0.01) under high-volume
      conditions. The addition of PEEP increased R further to -0.26 +/- 0.02 (P <
      0.01). All of these BEWs were reflected from a site ~3 cm downstream. During
      hypoxia, the BEW was maintained and a BCW appeared (R = +0.09 +/- 0.03) from a
      closed-end site ~9 cm downstream. The normal pulmonary arterial circulation in
      the open-chest dog is characterized by negative wave reflection tending to
      facilitate right ventricular ejection; this reflection increases with increasing
      blood volume and PEEP.

PMID- 11454597
TI  - Mechanisms underlying delayed afterdepolarizations in hypertrophied left
      ventricular myocytes of rats.
AB  - Cardiac hypertrophy was induced in rats by daily injection of isoproterenol (5
      mg/kg ip) for 7 days. Membrane voltage and currents were recorded using the whole
      cell patch-clamp technique in left ventricular myocytes from control and
      hypertrophied hearts. Ryanodine-sensitive delayed afterdepolarizations (DADs) and
      transient inward current (I(ti)) appeared in hypertrophied cells more often and
      were of larger amplitude than in control cells. DADs and I(ti) are carried
      principally by Na/Ca exchange with smaller contributions from a nonselective
      cation channel and from a Cl- channel. The latter is expressed only in
      hypertrophied myocytes. In hypertrophy, the density of caffeine-induced Na/Ca
      exchange current (I(Na/Ca)) was increased by 26%, sarcoplasmic reticulum (SR)
      Ca2+ content as assessed from the integral of I(Na/Ca) was increased by 30%, the
      density of Na-pump current (I(pump)) was reduced by 40%, and the intracellular
      Na+ content, measured by Na+-selective microelectrodes was increased by 55%. The
      results indicate that DADs and I(ti) are generated by spontaneous Ca2+ release
      from an overloaded SR caused by a downregulated Na pump and an upregulated Na/Ca
      exchange. These findings may explain the propensity for arrhythmias seen in this
      model of hypertrophy.

PMID- 11454598
TI  - Growth hormone reverses age-related cardiac myofilament dysfunction in rats.
AB  - We tested the hypotheses that aging is associated with a reduction in overall
      cardiac contractility and myofilament force generation that could be reversed
      with growth hormone (GH) replacement. Three groups of male Brown-Norway rats were
      studied: young (Y(SAL): 8 mo old, n = 13), old (O(SAL): 28 mo old, n = 13), and
      old GH-treated (O(GH): 28 mo old, n = 12; 300 microg bovine GH, twice a day for
      30 days). The left ventricular (LV) pressure-volume relation was derived in
      isolated hearts, after which isolated trabecular muscles from these hearts were
      permeabilized and maximal myofilament force generation (Fmax) was measured. LV
      developed pressures at a LV volume of 0.3 ml were significantly depressed with
      age: 84 +/- 6 vs. 71 +/- 6 mmHg (Y(SAL) vs. O(SAL), respectively, P = 0.001) and
      not restored by GH (69 +/- 4 mmHg). Fmax was reduced in the aged hearts: 47.5 +/-
      3.12 vs. 35.9 +/- 3.03 mN/mm2 (Y(SAL) vs. O(SAL), respectively, P = 0.014) but
      was restored with GH replacement to 46.7 +/- 3.12 mN/mm2 (O(SAL) vs. O(GH), P =
      0.021). Our results suggest that cellular myofilament contractility is reduced
      with aging and restored with GH replacement.

PMID- 11454599
TI  - Roles for platelet-activating factor and *NO-derived oxidants causing neutrophil
      adherence after CO poisoning.
AB  - Studies were conducted with rats to investigate whether platelet activating
      factor (PAF) and nitric oxide (*NO)-derived oxidants played roles in the initial
      adherence of neutrophils to vasculature in the brain after carbon monoxide (CO)
      poisoning. Before CO poisoning, rats were treated with the competitive PAF
      receptor antagonist WEB-2170 or with the peroxynitrite scavenger
      selenomethionine. Both agents caused significantly lower concentrations of
      myeloperoxidase in the brain after poisoning, indicating fewer sequestered
      neutrophils. Similarly, both agents reduced the concentration of nitrotyrosine,
      indicating less oxidative stress due to *NO-derived oxidants. There were no
      alterations in whole brain homogenate PAF concentration measured by immunoassay
      and bioassay, nor were there changes in phosphatidylcholine concentration.
      Immunohistochemical imaging showed PAF to be more heavily localized within
      perivascular zones after CO poisoning. Neutrophils colocalized with both PAF and
      nitrotyrosine in brains of rats killed immediately after CO poisoning. We
      conclude that qualitative changes in brain PAF are responsible for neutrophil
      adherence immediately after CO poisoning and that activated neutrophils trigger
      the initial rise in brain nitrotyrosine. Persistent PAF-mediated neutrophil
      adherence required production of *NO-derived oxidants because when oxidants were
      scavenged, neutrophil adherence was not maintained.

PMID- 11454600
TI  - Cardiac-directed overexpression of wild-type alpha1B-adrenergic receptor induces
      dilated cardiomyopathy.
AB  - Using transgenesis as a paradigm, we show here that alpha1-adrenergic receptors
      (alpha1AR) play an important role in cardiac homeostasis. Cardiomyocyte-specific
      overexpression of the alpha(1B)AR subtype resulted in the development of dilated
      cardiomyopathy and death at ~9 mo of age with typical signs of heart failure.
      Histological analyses showed the enlargement of all four cardiac chambers and
      cardiomyocyte disarray in the failing hearts. Transgenic animals showed increased
      left ventricular areas, as assessed by echocardiography. In addition, a
      progressive decrease in left ventricular systolic function was revealed. The
      abundance and activity of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) were
      reduced, and the ratio of phospholamban to SERCA2 was increased. alpha-Myosin
      heavy chain (MHC) mRNA was less abundant in older transgenic ventricles, whereas
      beta-MHC was induced in the failing hearts. Titin mRNA abundance was decreased at
      9 mo, whereas atrial natriuretic factor mRNA was elevated at all times. This
      model mimics structural and functional features of idiopathic dilated
      cardiomyopathy. The results of this study suggest that chronic alpha1AR activity
      is deleterious for cardiac function.

PMID- 11454601
TI  - Effects of erythrocyte aggregation and venous network geometry on red blood cell
      axial migration.
AB  - Axial migration of red blood cells in small glass tubes can cause blood viscosity
      to be effectively independent of shear rate. However, this phase separation may
      not occur to the same degree in the venous network due to infusion of cells and
      aggregates at branch points. To investigate this hypothesis, we followed
      trajectories of fluorescently labeled red blood cells in the venular network of
      the rat spinotrapezius muscle at normal and reduced flow with and without red
      blood cell aggregation. Cells traveling near the wall of an unbranched venular
      segment migrated approximately 1% of the longitudinal path length without
      aggregation and migrated slightly more with aggregation. Venular segment length
      between branch points averaged three to five times the diameter. Cells in the
      main vessel were shifted centrally by up to 20% of diameter at branch points,
      reducing the migration rate of cells near the opposite wall to <1% even in the
      presence of aggregation. We conclude that formation of a cell-free marginal layer
      in the venular network is attenuated due to the time dependence of axial
      migration and the frequent branching of the network.

PMID- 11454602
TI  - Erythrocyte margination and sedimentation in skeletal muscle venules.
AB  - Previous studies in skeletal muscle of the dog and cat have shown that venous
      vascular resistance changes inversely with blood flow and may be due mainly to
      red blood cell aggregation, a phenomenon present in these species. To determine
      whether red blood cell axial migration and sedimentation contribute to this
      effect, we viewed either vertically or horizontally oriented venules of the rat
      spinotrapezius muscle with a horizontally oriented microscope during acute
      arterial pressure reduction. With normal (nonaggregating) rat blood, reduction of
      arterial pressure did not significantly change the relative diameter of the red
      blood cell column with respect to the venular wall. After induction of red blood
      cell aggregation in the rat by infusion of Dextran 500, red blood cell column
      diameter decreased up to 35% at low pseudoshear rates (below approximately 5 s(
      1)); the magnitude was independent of venular orientation. In vertically oriented
      venules, the plasma layer was symmetrical, whereas in horizontally oriented
      venules, the plasma layer formed near the upper wall. We conclude that, although
      red blood cell axial migration and sedimentation develop in vivo, they occur only
      for larger flow reductions than are needed to elicit changes in venous
      resistance.

PMID- 11454603
TI  - Cyclooxygenase-2 does not mediate late preconditioning induced by activation of
      adenosine A1 or A3 receptors.
AB  - Recent studies have demonstrated that the adenosine A1 receptor agonist 2-chloro
      N6-cyclopentyladenosine (CCPA) and the adenosine A3 receptor agonist N6-(3
      iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) produce a delayed phase of
      protection against infarction similar to the late phase of ischemic
      preconditioning (PC). However, the mechanism for adenosine A1 or A3 receptor
      induced late PC remains unknown. The goal of this study was to determine whether
      the delayed cardioprotective effects of adenosine A1 or A3 receptors are mediated
      by cyclooxygenase-2 (COX-2), which is an obligatory mediator of ischemic PC. We
      found that COX-2 protein expression (Western blotting) did not increase 24 h
      after the administration of either CCPA (100 microg/kg iv) or IB-MECA (300
      microg/kg iv) compared with controls. To probe the role of constitutive COX-2
      expression, conscious rabbits were subjected to 30-min coronary occlusion
      followed by 72-h reperfusion. Twenty-four hours before the occlusion, the rabbits
      were pretreated with CCPA (100 microg/kg iv) or IB-MECA (300 microg/kg iv). Both
      CCPA and IB-MECA resulted in a marked (approximately 47%) reduction in infarct
      size vs. controls [36.2 +/- 4.0% of the risk region (n = 9), 31.2 +/- 4.7% (n =
      9), and 59.5 +/- 3.8% (n = 9), respectively; P < 0.05], similar to that induced
      by the late phase of ischemic PC [31.8 +/- 3.2% (n = 9)]. The selective COX-2
      inhibitor N-(2-[cyclohexyloxy]4-nitrophenyl)methanesulfonamide (NS-398, 5 mg/kg),
      which abolished the protective effect of ischemic late PC, failed to block the
      protection of either CCPA or IB-MECA, indicating that COX-2 does not mediate the
      delayed protection of either CCPA or IB-MECA [CCPA + NS-398, 29.1 +/- 3.4% (n =
      7); IB-MECA + NS-398, 34.9 +/- 2.9% (n = 8)]. NS-398 in itself did not affect
      infarct size [54.9 +/- 3.7% (n = 9)]. Taken together, these results demonstrate
      that, in contrast to ischemia-induced late PC, the mechanisms of adenosine A1 or
      A3 receptor-induced late PC is independent of COX-2.

PMID- 11454604
TI  - High-throughput assessment of calcium sensitivity in skinned cardiac myocytes.
AB  - Isolated permeabilized cardiac myocytes have been used in the study of
      myofilament calcium sensitivity through measurement of the isometric force-pCa
      curve. Determining this force-pCa relationship in skinned myocytes is relatively
      expensive and carries a high degree of variability. We therefore attempted to
      establish an alternative high-throughput method to measure calcium sensitivity in
      cardiac myocytes. With the use of commercially available software that allows for
      precise measurement of sarcomere spacing, we measured sarcomere length changes in
      unloaded skinned cardiac myocytes over a range of calcium concentrations. With
      the use of this technique, we were able to accurately detect acute increases or
      decreases in myofilament calcium sensitivity after exposure to 10 mM caffeine or
      5 mM 2,3-butanedione monoxime, respectively. This technique allows for the simple
      and rapid determination of myofilament calcium sensitivity in cardiac myocytes in
      a reproducible and inexpensive manner and could be used for high-throughput
      screening of pharmacological agents and/or transgenic mouse models for changes in
      myofilament calcium sensitivity.

PMID- 11454605
TI  - Nitric oxide-independent effects of tempol on sympathetic nerve activity and
      blood pressure in normotensive rats.
AB  - The role of the sympathetic nervous system in 4-hydroxy-2,2,6,6-tetramethyl
      piperidinoxyl (tempol)-induced cardiovascular responses in urethane-anesthetized,
      normotensive rats was evaluated. Tempol caused dose-dependent (30-300 micromol/kg
      iv) decreases in renal sympathetic nerve activity (RSNA), mean arterial blood
      pressure (MAP), and heart rate (HR). Similar responses were obtained after
      sinoaortic denervation and cervical vagotomy. These responses were not blocked
      following treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine
      (2.6 mg x kg(-1) x min(-1) iv for 5 min) or the alpha2-adrenergic receptor
      antagonist idazoxan (0.3 mg/kg iv bolus). Idazoxan blocked the effects of
      clonidine (10 miccrog/kg iv) on HR, MAP, and RSNA. Hexamethonium (30 mg/kg iv)
      inhibited RSNA, and tempol did not decrease RSNA after hexamethonium. The effects
      of tempol on HR and MAP were reduced by hexamethonium. In conclusion, depressor
      responses caused by tempol are mediated, partly, by sympathoinhibition in
      urethane-anesthetized, normotensive rats. Nitric oxide does not contribute to
      this response, and the sympathoinhibitory effect of tempol is not mediated via
      alpha2-adrenergic receptors. Finally, tempol directly decreases HR, which may
      contribute to the MAP decrease.

PMID- 11454614
TI  - Is self-fertilization an evolutionary dead end? Revisiting an old hypothesis with
      genetic theories and a macroevolutionary approach.
AB  - G. Ledyard Stebbins suggested that self-fertilization (selfing) may be an
      evolutionary dead end because it may result in the loss of genetic diversity and
      consequently preclude adaptation to changing environments. While the basic
      premise of selfing as a dead end is widely accepted, there have been few rigorous
      evaluations of the hypothesis. We examine the foundations of the dead-end
      hypothesis by considering theoretical advances in the study of mating-system
      evolution. We discuss theories predicting the irreversibility of self
      fertilization and the extinction of selfing lineages through the loss of adaptive
      potential and genetic degradation. In the second portion of the review, focusing
      on the irreversibility of selfing, we summarize the contribution of phylogenetic
      studies of mating-system evolution to determine if evolutionary history supports
      this well-established hypothesis. Most studies are in accord with the hypothesis;
      no single study unequivocally demonstrates the transition from highly selfing to
      outcrossing lineages. Finally, we discuss the problems encountered when
      phylogenetic studies rely on reconstruction of ancestral mating systems. To avoid
      some of these problems, we applied likelihood ratio tests of irreversibility of
      mating-system evolution to several data sets and found that current data sets are
      probably too small for this test.

PMID- 11454615
TI  - Architecture of the sperm cell of Psilotum.
AB  - In this correlated SEM (scanning electron microscope) and TEM (transmission
      electron microscope) investigation, we describe architectural details of the
      multiflagellated sperm cell of Psilotum nudum. Comparisons with other
      pteridophytes are made to (1) assess the placement of Psilotum among pteridophyte
      taxa and (2) evaluate structural modifications of sperm cells during land plant
      evolution. The released spermatozoid of Psilotum coils 2.0 revolutions and is
      outlined by a parallel band of up to 190 microtubules. The elongated nucleus is
      highly compacted and parallels the cellular coils with numerous mitochondria and
      starch-laden plastids distributed along its length. Along the anterior coil is an
      elaborate locomotory apparatus that includes ~36 flagella that are inserted into
      the cell by basal bodies. Subtending the basal bodies is the multilayered
      structure, which consists of a long narrow lamellar strip and an overlying band
      of microtubules. An elongated anterior mitochondrion underlies the multilayered
      structure. Additional amyloplasts and mitochondria are aggregated along the
      anterior coil in association with the locomotory apparatus, while a fibrous band
      encircles the leading edge of the cell. Salient features of this cell, including
      details of the locomotory apparatus, structure and position of organelles, and
      arrangement of the spline, are shared by spermatozoids of Equisetum and ferns
      (including eusporangiate and leptosporangiate taxa). Thus, this study provides
      morphological support for the hypothesis that Psilotum nudum is a member of an
      assemblage that includes ferns and Equisetum. However, the less streamlined
      architecture of Psilotum gametes and the lack of architectural features shared
      with any specific taxon examined to date suggest that Psilotum is an early
      divergent fern, with relatively remote affinities to Ophioglossaceae and
      Equisetaceae.

PMID- 11454616
TI  - Floral development in Schotia and Cynometra (Leguminosae: Caesalpinioideae:
      Detarieae).
AB  - Floral development was compared among several relatively unspecialized taxa in
      caesalpinioid tribe Detarieae: Cynometra webberi, an undescribed species of
      Cynometra, and three species of Schotia. These share a relatively unspecialized
      caesalpinioid flower type with no loss of organs, but some organ suppression.
      They also share the following characters: relatively small bracteoles in early
      stages, a circular floral apex, helical sepal initiation, and a nonmedian abaxial
      position of the first sepal initiated. Floral symmetry is radial. Order of
      initiation is helical among sepals in all. Order of petal initiation varies:
      helical in Schotia afra, unidirectional in Schotia brachypetala and S. latifolia,
      and simultaneous in Cynometra. Stamens are initiated unidirectionally in all
      except in the outer stamen whorl of Schotia afra, which is helical. Overlap of
      time of initiation between whorls occurs in S. brachypetala, S. latifolia, and
      Cynometra. The carpel initiates concurrently with the petals or directly
      thereafter in all. A tetramerous calyx results from fusion of the two upper
      (adaxial) sepal primordia. The carpel initiates ovules before marginal closure in
      both genera. Organ suppression includes one or two petals in Schotia and
      sometimes one in Cynometra.

PMID- 11454617
TI  - Genetic relatedness among developing seeds and intra fruit seed abortion in
      Dalbergia sissoo (Fabaceae).
AB  - Dalbergia sissoo, a wind-dispersed tropical tree, exhibits high intrafruit seed
      abortion. Of the four to five ovules in the flower, generally one and
      occasionally two or three develop to maturity. It has been proposed that the seed
      abortion is a consequence of intense sibling competition for maternal resources
      and that this competition occurs as an inverse function of the genetic
      relatedness among the developing seeds. Accordingly, developing seeds compete
      intensely when they are genetically less related but tend to develop together
      when genetically more related. We tested this hypothesis by comparing the genetic
      similarity among the pairs of seeds developing within a pod with that among (a)
      random pairs from the pool of all seeds, (b) random pairs from single-seeded
      pods, and (c) random pairs from two-seeded pods, using both randomly amplified
      polymorphic DNA (RAPD) and isozymes in five trees. We found that the pairs of
      seeds developing within a pod are genetically more similar than any random pairs
      of seeds in a tree. Thus the formation of two-seeded pods appear to be associated
      with increased genetic relatedness among the developing seeds. We discuss the
      results in the context of possible fitness advantages and then discuss the
      possible mechanisms that promote tolerance among related seeds.

PMID- 11454618
TI  - Phylogenetic analysis of tribe Salsoleae (Chenopodiaceae) based on ribosomal ITS
      sequences: implications for the evolution of photosynthesis types.
AB  - Diversity in photosynthetic pathways in the angiosperm family Chenopodiaceae is
      expressed in both biochemical and anatomical characters. To understand the
      evolution of photosynthetic diversity, we reconstructed the phylogeny of
      representative species of tribe Salsoleae of subfamily Salsoloideae, a group that
      exhibits in microcosm the patterns of photosynthetic variation present in the
      family as a whole, and examined the distribution of photosynthetic characters on
      the resulting phylogenetic tree. Phylogenetic relationships were inferred from
      parsimony analysis of nucleotide sequences of the internal transcribed spacer
      regions (ITS) of the 18S-26S nuclear ribosomal DNA of 34 species of Salsola and
      related genera (Halothamnus, Climacoptera, Girgensohnia, Halocharis, and
      Haloxylon) and representative outgroups from tribes Camphorosmeae (Camphorosma
      lessingii, Kochia prostrata, and K. scoparia) and Atripliceae (Atriplex
      spongiosa). A highly resolved strict consensus tree largely agrees with
      photosynthetic type and anatomy of leaves and cotyledons. The sequence data
      provide strong support for the origin and evolution of two main lineages of
      plants in tribe Salsoleae, with NAD-ME and NADP-ME C(4) photosynthesis,
      respectively. These groups have different C(4) photosynthetic types in leaves and
      different structural and photosynthetic characteristics in cotyledons.
      Phylogenetic relationships inferred from ITS sequences generally agree with
      classifications based on morphological data, but deviations from the existing
      taxonomy were also observed. The NAD-ME C(4) lineage contains species classified
      in sections Caroxylon, Malpigipila, Cardiandra, Belanthera, and Coccosalsola, and
      the NADP-ME lineage comprises species from sections Coccosalsola and Salsola.
      Reconstruction of photosynthetic characters on the ITS phylogeny indicates
      separate NAD-ME and NADP-ME lineages and suggests two reversions to C(3)
      photosynthesis. Reconstruction of geographic distributions suggests Salsoleae
      originated and diversified in central Asia and subsequently dispersed to Africa,
      Europe, and Mongolia. Inferred patterns and processes of photosynthetic evolution
      in Salsoleae should further our understanding of biochemical and anatomical
      evolution in Chenopodiaceae as a whole.

PMID- 11454619
TI  - New observations on the secondary chemistry of world Ephedra (Ephedraceae).
AB  - For several millennia, stem extracts of Ephedra (Ephedraceae, Gnetales) have been
      used as folk medicines in both the Old and New World. Some species were used in
      treatments of questionable efficacy for venereal disease in North America during
      the last century. Many Eurasian species produce phenylethylamine alkaloids,
      mostly ephedrine and pseudoephedrine, that interact with adrenergic receptors in
      the mammalian sympathetic nervous system. Asian Ephedra have been used recently
      in the clandestine manufacture of a street drug, methamphetamine. Although
      ephedrine alkaloids are not detectable in New World species of Ephedra, together
      with Asian species they contain other nitrogen-containing secondary metabolites
      with known neuropharmacological activity. Many mesic and particularly xeric
      species worldwide accumulate substantial amounts of quinoline-2-carboxylic acids,
      or kynurenates, in their aerial parts. Many species of Ephedra accumulate
      cyclopropyl amino acid analogues of glutamate and proline in their stems and
      roots, and particularly in the seed endosperm. Mesic species synthesize
      substantial amounts of three L-2-(carboxycyclopropyl)glycine stereomers rarely
      seen in nature. A cyclopropyl analogue of proline with known antimicrobial
      activity, cis-3,4-methanoproline, is found in large amounts in the stems and
      seeds of many Ephedra species. The ability to synthesize cyclopropyl amino acids
      may be an ancestral feature in the taxon. The natural function in the taxon of
      these three groups of secondary compounds remains to be established.

PMID- 11454620
TI  - cpDNA-RFLP in Ceramium (Rhodophyta): intraspecific polymorphism and species-level
      phylogeny.
AB  - Restriction fragment length polymorphism (RFLP) analysis of chloroplast (cp) DNA
      is a powerful tool for the study of microevolutionary processes in land plants,
      yet has not previously been applied to seaweed populations. We used cpDNA-RFLP,
      detected on Southern blots using labeled total plastid DNA, to search for
      intraspecific and intrapopulational cpDNA RFLP polymorphism in two species of the
      common red algal genus Ceramium in Ireland and Britain. In C. botryocarpum one
      polymorphism was detected in one individual among 18 from two populations. Twenty
      six individuals of C. virgatum from five populations at three locations exhibited
      a total of four haplotypes. One was frequent (80.8% of individuals); the others
      were rare (7.7, 7.7, and 4.2%) and were private to particular populations.
      Polymorphism was observed in two populations. The corrected mean was 2.26 +/-
      0.36 haplotypes per population, which was within the typical range determined for
      higher plants using similar techniques. The spatial distribution of haplotypes
      was heterogeneous, with highly significant population differentiation (P =
      0.00018; Fisher's exact test). Intraspecific polymorphism in C. virgatum had no
      impact on species-level phylogenetic reconstruction. This is the first
      unequivocal report of both intraspecific and intrapopulational cpDNA-RFLP
      polymorphism in algae.

PMID- 11454621
TI  - Implications of mating patterns for conservation of the endangered plant
      Eriogonum ovalifolium var. vineum (Polygonaceae).
AB  - Mating patterns have direct application to conservation because of their
      influence on structuring genetic diversity within and among populations and on
      maintaining that diversity over time. We measured population and family
      outcrossing rates, biparental inbreeding, correlation of outcrossed paternity,
      and inbreeding coefficients in six populations from throughout the ecological
      range of the endangered plant Eriogonum ovalifolium var. vineum using naturally
      pollinated families. The taxon was primarily outcrossed: population outcrossing
      rates averaged 0.80 (SE 0.03) and family outcrossing rates averaged 0.88 (SE
      0.03); neither rate varied among populations. Five population rates were
      significantly different from 1 while family rates differed from 1 in only one
      population. We found high correlated outcrossed paternity and evidence for
      biparental inbreeding in five populations each. As expected from the
      predominantly outcrossed mating system, levels of diversity were high and
      inbreeding coefficients among maternal individuals were low (averaging -0.05, SE
      0.12). Differences between inbreeding coefficients of progeny (average 0.21, SE
      0.06) and mothers indicated selection against homozygous offspring. These results
      indicate that it is important to maintain large populations to prevent increases
      in inbreeding and to maintain pollinator communities to facilitate outcrossing.

PMID- 11454622
TI  - Variation in summer dormancy in the lilioid geophyte Burchardia umbellata
      (Colchicaceae).
AB  - Plant dormancy is a form of phenotypic plasticity that minimizes exposure to
      seasonally stressful conditions. We examined variation in summer dormancy in two
      highland and two lowland populations of the lilioid geophyte Burchardia umbellata
      to test the prediction that facultative dormancy is advantageous in habitats with
      variable summer conditions. Consistent with this prediction fewer highland plants
      than lowland plants became dormant under wet common garden conditions. Also,
      significant among-family variance occurred within highland but not lowland
      populations, indicating genetic differences among and within populations. Most
      lowland plants became dormant when exposed to wet or dry conditions (~92%),
      indicating that dormancy was primarily obligate. In contrast, dormancy in
      highland plants increased from 44% under wet conditions to 93% under dry
      conditions, indicating that dormancy of some highland plants was facultative and
      induced by drought. Survival, growth, and flowering were reduced in lowland
      populations, and in dormant vs. nondormant highland plants, indicating costs of
      dormancy that could negate the advantages of dormancy under variable summer
      conditions. Summers in lowland populations are predictably hot and dry, favoring
      a phenotype that responds invariably to environmental cues that are correlated to
      future dry conditions. In highland populations, variable summer conditions
      probably maintain polymorphism in dormancy.

PMID- 11454623
TI  - Biogeography and origin of Lilium longiflorum and L. formosanum (Liliaceae)
      endemic to the Ryukyu Archipelago and Taiwan as determined by allozyme diversity.
AB  - Allozyme diversity on 13 isozyme loci was investigated for two bulbous species,
      Lilium longiflorum and L. formosanum, endemic to the subtropical archipelago of
      continental origin located in East Asia. Degrees of allozyme variability and
      divergence for L. longiflorum were very high for insular endemic species,
      indicating relatively longtime persistence of the present widespread distribution
      across many islands in this phenotypically little-changed species. Lilium
      formosanum exhibited rather lower variability and divergence than did L.
      longiflorum and was genetically close to the southern peripheral populations of
      L. longiflorum with 0.978 as its highest genetic identity value. Combined with
      other biological and insular geohistorical information, our results suggest that
      L. longiflorum was established around the end of the Pliocene when the current
      distribution area was still a continuous part of the ancient Asian continent, and
      L. formosanum was derived from southern populations of L. longiflorum around the
      late Pleistocene when the mainland of Taiwan was completely separated from the
      adjacent islands and the main continent. Depauperization of allozyme variability
      in some L. longiflorum populations was found on islands with lower altitudes.
      This reflects bottleneck effects after the complete or almost complete
      submergence of such low islands during the archipelago's development.

PMID- 11454624
TI  - The effect of maternal photoperiod on seasonal dormancy in Arabidopsis thaliana
      (Brassicaceae).
AB  - The maternal photoperiod at the time of seed maturation can predict the seasonal
      conditions of newly dispersed seeds. We investigated the effects of maternal
      photoperiod on seasonal dormancy in Arabidopsis thaliana using a set of F6
      recombinant inbred lines derived from a cross between individuals from two
      natural populations (Cal-0 and Tac-0) differing in cold requirements for
      germination. We grew 40 Cal * Tac lines in a long-day photoperiod (8 h of full
      spectrum light plus 8 h of low-fluence incandescent light) and a short-day
      photoperiod (8 h full spectrum light). We then exposed seeds from each family and
      maternal photoperiod to either a cold stratification treatment (4 degrees C, 21
      d) or no cold stratification. Both maternal photoperiod and progeny
      stratification influenced the percentage of seeds that germinated and the speed
      of germination. The short-day photoperiod caused increased responsiveness to
      stratification, with higher germination percentages and speeds in stratified
      seeds. Stratification influenced the expression of maternal photoperiod effects,
      such that short days increased germination percentage and speed in stratified
      seeds but inhibited germination in unstratified seeds. Families differed
      significantly in their plasticity to maternal photoperiod and stratification, but
      genetic variation for plasticity to maternal photoperiod was expressed only in
      unstratified seeds. Because the expression of maternal photoperiod effects and
      genetic variation for photoperiod effects depended on progeny stratification, the
      evolution of these maternal effects will depend on the seasonal environment
      experienced by progeny.

PMID- 11454625
TI  - A demographic analysis of fire-stimulated seedling establishment of Sarracenia
      alata (Sarraceniaceae).
AB  - Recurring fires are thought to be critical to maintaining populations of
      carnivorous plants in wet pine savannas. Nevertheless, the impact of fire on
      population dynamics of these unique and sometimes rare plants is poorly
      understood. In this study, I analyzed stage-structured matrices for Sarracenia
      alata. To examine the effects of fire-stimulated increases in seedling
      establishment, five matrices were constructed, which differed in fecundity rates
      associated with different fire frequencies (annual fires, 1/3, 1/7, 1/20, and
      0/20 yr). In addition, I analyzed the sensitivity of population growth and
      dynamics to changes in other vital rates. Fire-stimulated increases in fecundity
      were not necessary to maintain viable populations of Sarracenia alata. Although
      increases in fecundity increased population growth rate, all five fire
      frequencies (including the "no-fire" scenario) produced either stationary or
      increasing populations. Adding year-to-year stochasticity in vital rates did not
      alter these general trends. Population growth and decline were much more
      sensitive to reductions in the survival of large adult ramets (which were
      projected to have a life expectancy of 59 yr). Population growth was also more
      sensitive to changes in juvenile persistence than to juvenile growth, suggesting
      that conservative use of captured resources by juveniles has a greater impact on
      fitness than rapid growth and maturation. Given that a previous study showed that
      modest variation in fire frequency had no impact on either adult or juvenile
      survival, I conclude that Sarracenia alata relies on fire-regulated plasticity in
      allocation to pitchers to increase the survival and lifetime fecundity of
      iteroparous ramets.

PMID- 11454626
TI  - Molecular, physiological, and growth responses to sodium stress in C4 grasses
      from a soil salinity gradient in the Serengeti ecosystem.
AB  - The concentration of soil sodium (Na) is an important factor that influences
      species distribution in the Serengeti short-grass plains, Tanzania. Experiments
      were conducted to characterize physiological (growth, photosynthetic, nutrients,
      and water relations) and molecular (heat shock proteins and organic solutes)
      responses to high soil sodium in four Serengeti C(4) grasses. The species tested
      were Andropogon greenwayi and three species of Sporobulus, S. ioclados, S.
      kentrophyllus and S. spicatus. Andropogon greenwayi occurs on locations with low
      soil Na concentrations, S. ioclados on low to moderate, S. kentrophyllus moderate
      to high, and S. spicatus on soils with high Na concentration.Among all four
      species, short-term physiological and molecular responses to Na treatments (0,
      100, and 400 mmol/L Na) were correlated with their field soil Na concentrations.
      Sporobulus kentrophyllus and S. spicatus exhibited rapid molecular induction of
      heat shock proteins in response to experimental soil Na treatments within 24 h
      and had increased levels of proline within 96 h in contrast to A. greenwayi and
      S. ioclados. Photosynthetic rates and water relations were positively correlated
      with field soil Na concentrations and Hsp induction was clearly associated with
      photosynthetic tolerance. Long-term (6 wk) responses of the four species to Na
      treatment were consistent with the short-term responses to Na. Species that occur
      on low Na soils in the field did not survive past week 1 when treated with 400
      mmol/L Na and exhibited significant reductions in biomass when treated with 100
      mmol/L Na. Reduced biomass was associated with increased shoot tissue Na
      concentrations, and thus Na tolerance correlated with the Na concentrations of
      field leaf tissue. The results demonstrate that the community distribution of
      these species reflects their Na tolerance and that the observed physiological and
      molecular responses in tolerant species may have adaptive significance.

PMID- 11454627
TI  - Evolutionary trends in safety factors against wind-induced stem failure.
AB  - We explore the hypothesis that the safety factor against wind-induced stem
      failure remained high during early land plant evolution despite an evolutionary
      increase in height with concomitant increases in wind-induced drag forces,
      bending stresses, and moments. This hypothesis was examined for 17 Paleozoic
      plant species assuming that each (1) existed in a densely packed community of
      conspecifics with equivalent height, (2) coped with the same wind profile (where
      ambient wind speed decreased toward ground level), but (3) had different within
      canopy wind speeds depending on plant height and general morphology. Drag forces,
      stresses, and moments were computed, and a safety factor was calculated for each
      taxon using the quotient of its stem-tissue breaking stress and maximum wind
      induced bending stress.The highest factors of safety were calculated among the
      most ancient rhyniophyte and zosterophyllophyte species examined (e.g., Rhynia
      and Gosslingia), and, on average, decreased among the taller and geologically
      younger species. The tallest species examined (e.g., Archaeopteris and
      Diaphorodendron) had safety factors equal to or higher than those of some of
      their presumed ancestors (e.g., Psilophyton and Leclercqia). These trends were
      statistically more robust among rhyniophytes and their presumed descendants.Even
      though the results comply with the hypothesis, numerous limitations of our
      protocol exist (e.g., the requirement for reliable whole-plant reconstructions).
      These are discussed in terms of our theory. Nonetheless, we believe our theory
      and protocol afford a reasonable opportunity to explore the effects of wind on
      early plant evolution.

PMID- 11454628
TI  - Molecular and morphological reassessment of relationships within the Vittadinia
      group of Astereae (Asteraceae).
AB  - Morphological and ITS (internal transcribed spacer) sequence data for 40 species
      of the Austral-Pacific genera Camptacra, Kippistia, Minuria, Peripleura,
      Tetramolopium, and Vittadinia as well as one semiherbaceous species of Olearia
      were subjected to cladistic analysis, separately and together. Minuria,
      Peripleura, and Tetramolopium are paraphyletic as currently defined.
      Tetramolopium vagans from Australia appears to represent an undescribed genus.
      Both Kippistia suadefolia and Peripleura diffusa show close affinity to Minuria
      species, and Minuria macrorhiza appears to contain two distinct but closely
      related species. Vittadinia and the remaining species of Tetramolopium and
      Peripleura form a strong affinity group. The distribution of indels and the
      combined analysis each provide evidence that the Hawaiian and Cook Island species
      of Tetramolopium are descended from New Guinea species. The combined analysis
      also suggests that the Cook Island species T. mitiaroense is sister to the
      Hawaiian clade. Olearia arguta groups strongly with Camptacra and shows no close
      affinity with either of the arborescent species of Olearia used to root these
      analyses. Marked homoplasy among morphological characters indicates why generic
      delimitation in the group has been problematic.

PMID- 11454629
TI  - Historical biogeography of Melastomataceae: the roles of Tertiary migration and
      long-distance dispersal.
AB  - Melastomataceae and Memecylaceae are pantropically distributed sister groups for
      which an ndhF gene phylogeny for 91 species in 59 genera is here linked with
      Eurasian and North American fossils in a molecular clock approach to
      biogeographical reconstruction. Nine species from the eight next-closest families
      are used to root phylogenetic trees obtained under maximum likelihood criteria.
      Melastomataceae comprise ~3000 species in the neotropics, ~1000 in tropical Asia,
      240 in Africa, and 225 in Madagascar in 150-166 genera, and the taxa sampled come
      from throughout this geographic range. Based on fossils, ranges of closest
      relatives, tree topology, and calibrated molecular divergences, Melastomataceae
      initially diversified in Paloecene/Eocene times in tropical forest north of the
      Tethys. Their earliest (Eocene) fossils are from northeastern North America, and
      during the Oligocene and Miocene melastomes occurred in North America as well as
      throughout Eurasia. They also entered South America, with earliest (Oligocene)
      South American fossils representing Merianieae. One clade (Melastomeae) reached
      Africa from the neotropics 14-12 million years ago and from there spread to
      Madagascar, India, and Indochina. Basalmost Melastomataceae (Kibessieae,
      Astronieae) are species-poor lineages restricted to Southeast Asia. However, a
      more derived Asian clade (Sonerileae/Dissochaeteae) repeatedly reached Madagascar
      and Africa during the Miocene and Pliocene. Contradicting earlier hypotheses, the
      current distribution of Melastomataceae is thus best explained by Neogene long
      distance dispersal, not Gondwana fragmentation.

PMID- 11454630
TI  - Seed coat morphology and its systematic implications in Cyanea and other genera
      of Lobelioideae (Campanulaceae).
AB  - Recent surveys of seed coat morphology in Lobelioideae (Campanulaceae) have
      demonstrated the systematic utility of such data in the subfamily and led to a
      revision of the supraspecific classification of Lobelia. Expanding upon these
      studies, we examined via scanning electron microscopy 41 seed accessions,
      emphasizing lobelioid genera in which only one or no species had been examined.
      Most conformed to previously described testal patterns. However, five species of
      the endemic Hawaiian genus Cyanea, comprising the molecularly defined Hardyi
      Clade, had a unique testal pattern (here termed Type F), characterized by
      laterally compressed, almost linear, areoles with rounded, knob-like
      protuberances on the radial walls at opposite ends. This offered a convenient
      synapomorphy for recognition of a clade originally defined on a molecular basis.
      A second unique testal pattern was found in the related Hawaiian endemics
      Brighamia and Delissea, thus supporting their close relationship. In this type
      (here termed Type G), the seed coat is irregularly wrinkled (rugose), creating
      broad, rounded ridges that run more-or-less perpendicular to the long axis of the
      seed and thus to the long axis of the testal cells. Seed coat morphology also
      supported the monophyly of all 124 species of Hawaiian Lobelioideae and their
      probable derivation from Asian species of Lobelia subg. Tupa. Additional studies
      supported close relationships between (1) the neotropical genera Centropogon and
      Siphocampylus; (2) the western American genera Legenere and Downingia; and (3)
      Jamaican Hippobroma and Lobelia sect. Tylomium, a group endemic to the West
      Indies.

PMID- 11454631
TI  - Assessing the potential for the stomatal characters of extant and fossil Ginkgo
      leaves to signal atmospheric CO2 change.
AB  - The stomatal density and index of fossil Ginkgo leaves (Early Jurassic to Early
      Cretaceous) have been investigated to test whether these plant fossils provide
      evidence for CO(2)-rich atmosphere in the Mesozoic. We first assessed five
      sources of natural variation in the stomatal density and index of extant Gingko
      biloba leaves: (1) timing of leaf maturation, (2) young vs. fully developed
      leaves, (3) short shoots vs. long shoots, (4) position in the canopy, and (5)
      male vs. female trees. Our analysis indicated that some significant differences
      in leaf stomatal density and index were evident arising from these
      considerations. However, this variability was considerably less than the
      difference in leaf stomatal density and index between modern and fossil samples,
      with the stomatal index of four species of Mesozoic Ginkgo (G. coriacea, G.
      huttoni, G. yimaensis, and G. obrutschewii) 60-40% lower than the modern values
      recorded in this study for extant G. biloba. Calculated as stomatal ratios (the
      stomatal index of the fossil leaves relative to the modern value), the values
      generally tracked the CO(2) variations predicted by a long-term carbon cycle
      model confirming the utility of this plant group to provide a reasonable measure
      of ancient atmospheric CO(2) change.

PMID- 11454632
TI  - Dipteronia (Sapindaceae) from the Tertiary of North America and implications for
      the phytogeographic history of the Aceroideae.
AB  - The fossil record of Dipteronia, the sister genus of Acer, is reviewed based on
      diagnostic winged fruits from the Tertiary of western North America. Today the
      genus is endemic to eastern Asia with two extant species in central and southern
      China, but it is well represented in the Tertiary of western North America,
      ranging from the Paleocene to the Oligocene with the greatest number of
      occurrences in the middle to late Eocene. There are no known fossil occurrences
      outside of North America. The fossil fruits, assigned to the new species D.
      brownii sp. nov., are smaller than those of both living species and were
      tricarpellate as well as bicarpellate in contrast to the modern species, which
      are almost exclusively bicarpellate. The tricarpellate condition may be
      plesiomorphic for Dipteronia and perhaps Aceroideae. The area of origin for
      Dipteronia is unknown, but it seems likely to have been either Asia or North
      America, with the genus crossing Beringia in the Paleogene.

PMID- 11454633
TI  - Development of sterile ovules on bisexual cones of Gnetum gnemon (Gnetaceae).
AB  - Angiosperms and Gnetales (Ephedra, Gnetum, Welwitschia) represent the only seed
      plants that regularly produce bisexual cones. Unfortunately, the fertility and
      function of ovules formed on bisexual cones of Gnetales have remained unclear.
      Some reports indicate that the ovules are sterile while others indicate that they
      may develop into seeds. This study demonstrates three different developmental
      patterns of ovules formed on bisexual cones of Gnetum gnemon. Type I ovules did
      not develop at all after pollination and represented the majority of ovules on
      each cone. Type II ovules enlarged slightly after pollination due to the
      enlargement of nucellar tissue. Type III ovules were typically found on the
      terminal whorl and developed into seed-like structures. The enlargement was due
      to proliferation of megagametophyte tissue. Sectioned material revealed that
      megagametophytes show altered development compared to those found in functional
      female ovules. None of the ovules studied contained embryos, and thus all were
      sterile. Densitometry of 4',6-diamidino-2-phenylindole (DAPI)- stained sections
      revealed that megagametophyte nuclei formed in the sterile ovules are unreduced
      (diploid) and thus do not form viable female gametes.

PMID- 11454634
TI  - Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis.

PMID- 11454635
TI  - Stress fracture in long term methotrexate treatment for psoriatic arthritis.

PMID- 11454636
TI  - Multiple choice question quiz: a valid test for needs assessment in CME in
      rheumatology and for self assessment.
AB  - Drawing from experience in Switzerland, a test of 60 multiple choice questions
      covering the entire area of rheumatology was constructed and used at the
      international symposium of rheumatology, EULAR, Geneva 1998. It was introduced as
      a multiple choice question game, the language was English, and the level of
      acceptance was very high. Language posed only occasional problems. The
      reliability of the test for internal consistency was high (Cronbach alpha 0.852).
      One of the main target groups, the private practitioners, was the largest group
      of rheumatologists (nearly 50%). Evaluative statements of the participants
      indicate that it was a highly relevant test for rheumatology. This test is a
      valuable way for needs assessment in continuing medical education and for self
      assessment. Importantly, it has been shown that such a test can be conducted at
      an international level.

PMID- 11454637
TI  - Focal sialadenitis in patients with ankylosing spondylitis and
      spondyloarthropathy: a comparison with patients with rheumatoid arthritis or
      mixed connective tissue disease.
AB  - OBJECTIVES: To investigate the occurrence of and risk factors for focal
      sialadenitis in patients with rheumatoid arthritis (RA), mixed connective tissue
      disease (MCTD), ankylosing spondylitis (AS), and spondyloarthropathy (SpA).
      METHODS: A total of 85 patients (25 with RA, 19 with MCTD, 19 with AS, 22 with
      SpA) participated in the study. Each patient filled out a questionnaire for eye
      and oral symptoms and for the use of medication, and was interviewed; other tests
      included Schirmer's test, laboratory tests, collection of unstimulated and
      stimulated whole saliva, and minor salivary gland biopsy. A focus score of > or
      =1 was regarded as an indicator of focal sialadenitis. RESULTS: Focal
      sialadenitis was observed in 68% (57/84) of all patients. It affected 80% (20/25)
      of the patients with RA, 94% (17/18) of those with MCTD, 58% (11/19) of those
      with AS, and 41% (9/22) of those with SpA (chi(2) test, p=0.0013). Salivary
      secretion correlated negatively with the focus scores-that is, severity of focal
      sialadenitis. Patients with focal sialadenitis had both decreased salivary
      secretion and decreased tear secretion significantly more often than did patients
      without (chi(2) test, p=0.0074 and p=0.048 respectively). Patients with positive
      rheumatoid factor (RF), antinuclear antibodies (ANA), or SSA or SSB antibodies
      had sialadenitis significantly more often than did patients with negative
      antibodies. In the subgroup of patients with AS or SpA, no associations were
      found between focal sialadenitis and the presence of these antibodies.
      CONCLUSION: In addition to patients with RA or MCTD, focal sialadenitis also
      affects a very high proportion of patients with AS or SpA. Focus scores are
      significantly higher in patients with RA or MCTD than in those with AS or SpA. A
      significant association exists between focal sialadenitis and RF, ANA, SSA and
      SSB. However, in the subgroup of patients with AS or SpA, no associations were
      found between focal sialadenitis and serological markers or clinical symptoms.

PMID- 11454638
TI  - Impaired Th1 cytokine production in spondyloarthropathy is restored by anti
      TNFalpha.
AB  - OBJECTIVES: To evaluate the effect of anti-TNFalpha on the Th1 and Th2 cytokines
      in patients with spondyloarthropathy (SpA). METHODS: Peripheral blood mononuclear
      cells (PBMC) were obtained from 20 patients with active SpA treated with
      infliximab (5 mg/kg). For comparison, PBMC were also obtained from 15 healthy
      controls and 19 patients with active rheumatoid arthritis (RA). After stimulation
      with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and
      interferon (IFN)gamma were determined in CD3+ T cells and in CD3+/CD56+ natural
      killer (NK) T cells by flow cytometry. RESULTS: At baseline the percentage of T
      cells positive for IFNgamma (p=0.020) and IL2 (p=0.046) was decreased in patients
      with SpA compared with healthy controls, while IL10 (p=0.001) was increased. This
      cytokine profile, confirmed by the mean fluorescence intensities (MFI), was more
      pronounced in CD3+/CD8- cells and contrasted with higher IL2 production in RA. NK
      T cells, characterised by high IL4 and IL10 numbers, were also increased in
      patients with SpA (p=0.017). Treatment with infliximab induced a significant and
      persistent increase in IFNgamma and IL2 in patients with SpA. Moreover, there was
      a transient decrease in IL10 and NK T cells in patients with high baseline
      values, resulting in values comparable with those of healthy controls. This
      switch in cytokine profile was seen in both the CD3+/CD8- and CD3+/CD8+ subsets.
      CONCLUSIONS: Before treatment patients with SpA had an impaired Th1 cytokine
      profile compared with healthy controls and patients with RA. TNFalpha blockade
      induced restoration of the Th1 cytokines, resulting in a normal cytokine balance.
      These data confirm the effect of anti-TNFalpha on the immune changes in SpA, and
      provide insights into the mechanisms involved in TNFalpha blockade.

PMID- 11454639
TI  - A case-control study to investigate the relation between low and moderate levels
      of physical activity and osteoarthritis of the knee using data collected as part
      of the Allied Dunbar National Fitness Survey.
AB  - BACKGROUND: Physical activity is being recommended as an intervention for
      seemingly almost universal improvements to health. A potential concern with this
      recommendation for increased exercise is that some believe increased levels of
      activity may lead to increased incidence of osteoarthritis of the knee (knee OA),
      as a result of accelerated "wear and tear" of the major joints. OBJECTIVE: To
      investigate the hypothesis that the occurrence of knee OA may be related to the
      duration of participation in some forms of sport and active recreation. METHODS:
      The relation between habitual exercise, reported by a cross section of people
      surveyed in England, and self reported knee OA was investigated. Data were
      derived from the Allied Dunbar National Fitness Survey (1990-91). A matched
      retrospective case-control design was used and a new exposure classification
      system which categorised different grades of activities for different time
      periods for each subject's lifetime participation in regular physical activities
      was developed. Additional data on knee injuries sustained and bodily composition
      were also included in a multivariate analysis. RESULTS: From 4316 people
      originally interviewed, 216 eligible cases (66 men, 150 women) were identified
      (mean age 57.1). Each case was matched to four controls. When habitual
      sport/exercise participation were examined during a subject's life, only exposure
      to regular long walks and being physically active between the ages of 20 and 24
      suggested any association with developing knee OA later in life. The only strong
      association found was a greatly increased risk of knee OA having previously
      sustained a knee injury (p<0.01, odds ratio 8.0 (95% confidence interval 2.0 to
      32.0)). CONCLUSIONS: There was little evidence to suggest that increased levels
      of regular physical activity throughout life lead to an increased risk of knee OA
      later in life. Previous knee injury was associated with an increased risk of knee
      OA. Additionally, most injuries were caused through participation in physical
      activities. Hence, when deciding on participation in activities, it is worth
      taking the likelihood of joint injury into consideration, as the chance of injury
      is greater in some activities than others.

PMID- 11454640
TI  - Valgus deformity and proximal subluxation of the rheumatoid elbow: a radiographic
      15 year follow up study of 148 elbows.
AB  - OBJECTIVE: To evaluate the nature of positional changes of humeroulnar (HU) and
      humeroradial (HR) joints in a cohort of 74 patients with seropositive and erosive
      rheumatoid arthritis (RA) followed up prospectively. METHODS: At the 15 year
      follow up standard anteroposterior and lateral radiographs of 148 elbow joints
      were evaluated. The mediolateral HU angle of the elbow was measured from
      anteroposterior radiographs. The proximal subluxation of the HU joint was
      measured from lateral radiographs as the distance between the posterior aspect of
      the olecranon process and the posterior surface of the humerus. The
      anteroposterior subluxation of the HR joint was measured from lateral radiographs
      as the relation of the midpoint of head of the radius to the midpoint of the
      capitellum of the humerus. Destruction of the elbow joints was assessed with the
      Larsen method on a scale of 0 to 5 and compared with the measurements. RESULTS:
      Mean HU angle in 148 elbows of patients with RA was 11.5 degrees (SD 6.1), range 
      21 degrees (varus) to 34 degrees (valgus); 9.9 degrees (SD 4.3) in men and 12.0
      degrees (SD 6.4) in women. The mean HU angle, 14.4 degrees (SD 6.0) of the
      affected joints (Larsen grades 2-4), showed more valgus than the mean 9.8 degrees
      (SD 2.5) of the non-affected (Larsen grades 0 to 1) joints; totally destroyed and
      unstable Larsen 5 joints were excluded. Mean HU and HR subluxations, 2.0 mm (SD
      3.8) and 0.8 mm, of the affected joints (Larsen 2-5) were greater than the means,
      -1.1 mm (SD 1.5) and -0.4 mm (SD 0.9), of the non-affected joints. Both the HU
      proximal subluxation and the HR anterior subluxation correlated, r(s)=0.64 (95%
      CI 0.53 to 0.73 ) and r(s)=0.48 (95% CI 0.34 to 0.60), with the destruction of
      the elbow joint. CONCLUSIONS: The elbow seems to turn into valgus during
      rheumatoid destruction and excision of the radial head may speed up this process.
      However, totally unstable Larsen grade 5 joints may also have varus deformity
      owing to mutilating bone destruction. The ulna subluxates proximally in relation
      to the humerus, whereas the radius moves slightly anteriorly as a consequence of
      elbow involvement.

PMID- 11454641
TI  - Low field dedicated magnetic resonance imaging in untreated rheumatoid arthritis
      of recent onset.
AB  - OBJECTIVE: To compare a low field dedicated extremity magnetic resonance imaging
      system (E-MRI) with x ray and clinical examination, in the detection of
      inflammation and erosive lesions in wrist and metacarpophalangeal (MCP) joints in
      newly diagnosed, untreated rheumatoid arthritis (RA). PATIENTS AND METHODS:
      Twenty five patients (disease duration < or =1 year) and three healthy controls
      entered the study. An x ray examination and MRI (before and after intravenous
      injection of a contrast agent) of the 2nd-5th MCP joints and the wrist was
      performed. The number of erosions on x ray examination and MRI was calculated,
      and synovitis in the MCP joints and wrists was graded semiquantitatively.
      RESULTS: E-MRI detected 57 bone erosions, whereas only six erosions were
      disclosed by x ray examination (ratio 9.5:1). Synovial hypertrophy grades were
      significantly higher in RA joints with clinical signs of joint inflammation-that
      is, swelling and/or tenderness (median 3, 5th-95th centile 1-4) than without
      these clinical signs (median 2, 5th-95th centile 1-3), p < 0.001. 51% of the
      joints without clinical signs of synovitis showed synovial hypertrophy on E-MRI.
      There was a positive correlation between MRI scores of synovitis and the number
      of erosions detected by MRI in the MCP joints (Spearman r(s) = 0.31, p < 0.01).
      No healthy controls had erosions or synovitis on MRI. CONCLUSION: Joint
      destruction starts very early in RA and E-MRI allows detailed evaluation of
      inflammatory and destructive changes in wrists and MCP joints in patients with
      incipient RA.

PMID- 11454642
TI  - Specific glycosylation of alpha(1)-acid glycoprotein characterises patients with
      familial Mediterranean fever and obligatory carriers of MEFV.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is a periodic febrile disorder,
      characterised by fever and serositis. The acute phase response during attacks of
      FMF results from the release of cytokines, which in turn induce increased
      expression and changed glycosylation of acute phase proteins. A recent study
      indicated that attacks in FMF are accompanied by a rise of plasma concentrations
      of serum amyloid A (SAA) and C reactive protein (CRP), which remain significantly
      raised during remission relative to healthy controls. Another study suggested
      that obligatory heterozygotes also display an inflammatory acute phase response.
      OBJECTIVE: To determine the state of inflammation in homozygotic and
      heterozygotic MEFV genotypes. METHODS: CRP and SAA were studied by enzyme linked
      immunosorbent assay (ELISA). The glycosylation of the acute phase protein,
      alpha(1)-acid glycoprotein (AGP), was visualised with crossed
      affinoimmunoelectrophoresis with concanavalin A as diantennary glycan-specific
      component and Aleuria aurantia lectin as fucose-specific affinity component.
      RESULTS: FMF attacks were associated with an increase (p<0.05) in the serum
      inflammation parameters CRP, SAA, and AGP. The glycosylation of AGP showed an
      increase (p<0.05) in fucosylated AGP glycoforms, whereas the branching of the
      glycans remained unaffected. The glycosylation of AGP in the MEFV carrier group,
      compared with that in a healthy control group, was characterised by a significant
      increase (p<0.05) in branching of the glycans, whereas the fucosylation remained
      unaffected. CONCLUSION: The findings suggest an FMF-specific release of
      cytokines, resulting in a different glycosylation of AGP between a homozygotic
      and heterozygotic MEFV genotype.

PMID- 11454643
TI  - Culture of chondrocytes in alginate surrounded by fibrin gel: characteristics of
      the cells over a period of eight weeks.
AB  - OBJECTIVE: To produce tissue engineered cartilage by human articular chondrocytes
      in vitro for further use in in vivo manipulations for the treatment of cartilage
      defects. METHODS: Human articular chondrocytes were cultured in 0.5%, 1.0%, and
      2.0% of alginate for up to four weeks. The optimal concentration of an alginate
      matrix for cell replication and for aggrecan synthesis by chondrocytes was
      determined. DNA content in the different culture conditions was measured after
      two and four weeks. Aggrecan synthesis rates and accumulation in the surrounding
      extracellular matrix were assessed by [(35)S]sulphate incorporation after the
      same periods of culture. To follow the outgrowth of chondrocytes from the
      alginate beads, chondrocytes were cultured for four weeks in 0.5 or 1.0% alginate
      surrounded by 0.25 or 0.5% fibrin gel. DNA content of each culture was measured
      after different culture periods. Finally, human chondrocytes in 1.0% alginate
      beads were embedded in 0.5% fibrin gel for eight weeks. Immunohistochemical
      analysis for aggrecan, type I and II collagen was performed weekly. RESULTS: At
      two weeks the DNA content in each culture significantly increased in 0.5 and 1.0%
      alginate cultures in comparison with baseline values. This increase continued
      until week 4 at the three alginate concentrations. Aggrecan synthesis at two
      weeks was highest in 0.5 and 1.0% alginate cell cultures. At four weeks aggrecan
      synthesis rates decreased independently of the alginate concentrations. Aggrecan
      mainly accumulated in the interterritorial matrix. Proliferation of chondrocytes
      in alginate and outgrowth of these cells in the surrounding fibrin gel were
      evident throughout the culture period. The accumulation of aggrecan and type II
      collagen around the cells, in alginate as well as in fibrin gel, gradually
      increased over the culture period. Type I collagen appeared after six weeks in
      alginate and in the surrounding fibrin. CONCLUSION: Human chondrocytes
      proliferate in this culture system, show an outgrowth into the surrounding
      fibrin, and synthesise a cartilage-like matrix for up to eight weeks.

PMID- 11454644
TI  - Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1*
      alleles in Peruvian patients with rheumatoid arthritis.
AB  - OBJECTIVE: To study the association between rheumatoid arthritis (RA) and HLA and
      tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in
      comparison with ethnically similar controls. METHODS: Seventy nine patients with
      RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA
      DQA1, HLA-DQB1, and TNFalpha and TNFbeta alleles using PCR amplification.
      Clinical severity was assessed as mild, moderate, or severe in 35 of the
      patients. RESULTS: TNFalpha6 showed the strongest association with disease
      susceptibility. The TNFalpha6 allele was more common in patients than in controls
      (p<0.0076) and the proportion of patients with at least one copy of this allele
      was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the
      shared epitope sequence, only the DRB1*1402 allele was significantly increased in
      patients compared with controls (p<0.0311), as was the proportion of patients
      with at least one copy of this allele (p<0.0232, relative risk 2.74). In
      contrast, the overall frequency of alleles with the shared epitope was not
      different in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301
      DQA1*0401 was significantly more common in patients. TNFalpha6 was more common in
      patients whether or not they had this haplotype. None of the 11 patients lacking
      the TNFalpha6 allele had severe disease. CONCLUSIONS: This study shows for the
      first time that TNF gene polymorphism is associated with susceptibility to RA in
      a non-white population. TNFalpha6 and HLA-DRB1*1402 independently conferred
      significantly increased risk in Peruvian mestizo patients.

PMID- 11454645
TI  - Gastric antral vascular ectasia in systemic sclerosis: complete resolution with
      methylprednisolone and cyclophosphamide.
AB  - A case of severe, transfusion dependent anaemia in a 72 year old woman, which on
      endoscopy was found to be due to gastric antral vascular ectasia (GAVE), is
      reported. Repeated endoscopic sclerotherapy was ineffective. She subsequently
      developed Raynaud's phenomenon and on further investigation was found to have
      classical systemic sclerosis with lung involvement. Treatment with pulses of
      intravenous methylprednisolone and cyclophosphamide resulted in significant
      improvement in her pulmonary function tests and skin score. Coincidentally, her
      haemoglobin stabilised and further endoscopic examinations were normal. This is
      the first report of cyclophosphamide and methylprednisolone leading to complete
      and sustained resolution of GAVE in association with systemic sclerosis.

PMID- 11454646
TI  - Value of clinical factors in selecting postmenopausal women with rheumatoid
      arthritis for bone densitometry.
AB  - OBJECTIVE: Criteria to decide which patients with rheumatoid arthritis (RA)
      should be examined by dual energy x ray absorptiometry (DXA) are currently not
      available. The rheumatologists from Amsterdam have proposed preliminary criteria
      based on clinical risk factors (age, disease activity, and functional status).
      These criteria are preliminary and not widely accepted but might be helpful in
      practice. The value of the proposal in a group of Spanish postmenopausal women
      with RA is analysed. METHODS: DXA (lumbar spine and femoral neck) was performed
      in 128 patients recruited from a clinical setting, and the proposed criteria were
      applied. T and Z scores were established for a Spanish reference population.
      RESULTS: The mean (SD) age of the patients was 61.3 (10.7) and mean duration of
      the postmenopausal period 14.5 (10.1) years. Mean duration of RA was 13.7 (7.7)
      years. Mean C reactive protein was 22 (21) mg/l; mean erythrocyte sedimentation
      rate 26 (18) mm/1st h; and mean Health Assessment Questionnaire score 1.25
      (0.79). Ninety (70%) patients fulfilled the proposed criteria. Their sensitivity
      for the diagnosis of osteoporosis (T score < or =-2.5 SD) was 86% and their
      specificity, 43%. Positive predictive value was 54% and negative predictive
      value, 79%. CONCLUSIONS: The proposed criteria seem a good screening method for
      the selection of those patients with RA whose bone mineral density should be
      assessed as the sensitivity and negative predictive value are acceptable.

PMID- 11454647
TI  - Clonal analysis of B cells in the osteoarthritis synovium.
AB  - OBJECTIVES: Cellular and humoral immunity to collagen and cartilage proteoglycan
      were shown in patients with osteoarthritis (OA). Inflammatory infiltration
      containing T and B lymphocytes and macrophages, which are HLA-DR positive, is
      often seen in the synovial membrane of patients with OA. An analysis of the DNA
      restriction enzyme patterns of T lymphocytes from the OA synovium showed an
      oligoclonal pattern of T cell receptor beta chain gene rearrangements. No similar
      studies of B cell clonality have previously been performed. This study aimed at
      determining the clonal characteristics of the B cells in the OA synovium.
      METHODS: A reverse transcriptase-polymerase chain reaction of the immunoglobulin
      transcripts of B cells in the synovial membranes from six patients with OA was
      performed and the products were analysed by a single strand conformation
      polymorphism analysis. RESULTS: Several dominant bands were seen in all samples
      and some of the dominant bands were common among the two or three separate
      regions of each synovial sample. CONCLUSION: Infiltrated B cells are oligoclonal,
      and an antigen driven immune response may play a part in the progression of the
      disease process in OA.

PMID- 11454648
TI  - Prevalence of TTV DNA and GBV-C RNA in patients with systemic sclerosis,
      rheumatoid arthritis, and osteoarthritis does not differ from that in healthy
      blood donors.
AB  - OBJECTIVE: To determine the prevalence of GB virus-C (GBV-C) RNA and TT virus
      (TTV) DNA in patients with systemic sclerosis (SSc), rheumatoid arthritis (RA),
      and osteoarthritis (OA) as well as to compare the autoantibody pattern in
      patients with SSc with and without evidence of viral infection. PATIENTS AND
      METHODS: The study included 168 patients (84 SSc, 41 RA, and 43 OA) diagnosed
      according to the American College of Rheumatology criteria and 122 volunteer
      blood donors. The presence of GBV-C RNA and TTV DNA in serum was assessed by
      nested reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-nested
      PCR, respectively. Autoantibodies in patients with SSc were determined by enzyme
      linked immunosorbent assay (ELISA) and Hep-2 immunofluorescence. RESULTS: TTV-DNA
      was detected in 10/84 (12%) patients with SSc, 9/41 (22%) patients with RA, 3/43
      (7%) patients with OA, and 16/122 (13%) blood donors. GBV-C RNA was present in
      4/84 (5%) patients with SSc, 2/43 (5%) patients with OA, and 5/122 (4%) blood
      donors. No patient with RA was positive for GBV-C RNA. One patient with SSc and
      one patient with OA showed a double infection with GBV-C and TTV. 74/84 (88%)
      patients with SSc were positive for at least one autoantibody species tested:
      18/84 (21%) showed anticentromeric autoantibodies, 55/84 (66%) a speckled (36/84
      (43%) fine, 19/84 (23%) coarse), and 20/84 (24%) a homogeneous nuclear Hep-2
      pattern, and 21/84 (25%) had antinucleolar autoantibodies. Anti-Scl-70 antibodies
      were found in 31/84 (37%) and anti-RNP antibodies in 5/84 (6%) patients with SSc.
      No differences in the autoantibody pattern in patients with SSc with or without
      viral infection could be detected. CONCLUSION: The prevalence of GBV-C RNA and
      TTV DNA in serum samples from patients with SSc, RA, and OA was low and
      comparable with that in blood donors. A continuing infection with TTV and or GBV
      C was not associated with a significant change in the autoantibody pattern in
      patients with SSc. These data provide no evidence for an association between GBV
      C and/or TTV infections and SSc and/or arthritis (RA and OA).

PMID- 11454650
TI  - Effect of cyclosporin A and its vehicle on cardiac and skeletal muscle
      mitochondria: relationship to efficacy of the respiratory chain.
AB  - Although cyclosporin (CsA) is considered to be the best immunosuppressive
      molecule in transplantation, it has been suspected to alter mitochondrial
      respiration of various tissues. We evaluated the acute effect of CsA and its
      vehicle on maximal oxidative capacity (V(max)) of cardiac, soleus and
      gastrocnemius muscles of rats by an oxygraphic method in saponin skinned muscle
      fibres. The effects of Sandimmun (a formulation of CsA), vehicle of Sandimmun
      (cremophor and ethanol (EtOH)), CsA in EtOH and EtOH alone were tested.
      Increasing concentrations (5 - 20 - 50 - 100 microM) of CsA (or vehicles) were
      used. Sandimmun profoundly altered the V(max) of all muscles. For example, at 20
      microM, inhibition reached 18+/-3, 23+/-5, 45+/-5%, for heart, soleus and
      gastrocnemius respectively. There were only minor effects of CsA diluted in EtOH
      and EtOH alone on V(max) of cardiac muscle. Because the effects of vehicle on
      V(max) were similar or higher than those of Sandimmun, the inhibition of
      oxidative capacity could be entirely attributed to the vehicle for all muscles.
      Next, we investigated the potential sites of action of the vehicle on the
      different complexes of the mitochondrial respiratory chain by using specific
      substrates and inhibitors. The vehicle affected mitochondrial respiration mainly
      at the level of complex I ( approximately -85% in skeletal muscles, and -32% in
      heart), but also at complex IV ( approximately -26% for all muscles). The
      mechanism of action of the vehicle on the mitochondrial membrane and the
      implications for the clinical use of immunosuppressive drugs are discussed.

PMID- 11454651
TI  - In vivo pharmacology of BIIR 561 CL, a novel combined antagonist of AMPA
      receptors and voltage-dependent Na(+) channels.
AB  - Glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) subtype and voltage-gated Na(+) channels are associated with diseases
      of the central nervous system characterized by neuronal over-excitation as in
      epilepsy or cerebral ischaemia. In animal models, AMPA receptor antagonists and
      Na(+) channel blockers provide protection in these conditions. Dimethyl-[2-[2-(3
      phenyl-[1,2,4]oxadiazol-5-yl)-phenoxyl]-ethyl]-amine hydrochloride (BIIR 561 CL)
      combines both, AMPA receptor - and Na(+) channel blocking properties in one
      molecule. Here, BIIR 561 CL was investigated in vivo. BIIR 561 CL protected mice
      against AMPA-induced toxicity with an ED(50) value of 4.5 mg kg(-1) following
      subcutaneous (s.c.) administration. A 0.1% solution of BIIR 561 CL provided local
      anaesthesia in the corneal reflex test in rabbits. In mice, the compound
      prevented tonic seizures in the maximal electroshock (MES) model with an ED(50)
      value of 3.0 mg kg(-1) s.c. In amygdala-kindled rats, BIIR 561 CL inhibited
      seizures at doses of 3 and 11 mg kg(-1) following intraperitoneal (i.p.)
      injection. The data show that the combination of blocking AMPA receptor- and
      voltage-gated Na(+) channels in one molecule induces effective protection in
      animal models of neuronal over-excitation.

PMID- 11454649
TI  - Biological significance of agmatine, an endogenous ligand at imidazoline binding
      sites.

PMID- 11454652
TI  - SB-272183, a selective 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptor antagonist in
      native tissue.
AB  - A novel compound, SB-272183 (5-Chloro-2, 3-dihydro-6-[4-methylpiperazin-1-yl]-1[4
      pyridin-4-yl]napth-1-ylaminocarbonyl]-1H-indole), has been shown to have high
      affinity for human 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors with pK(i) values of
      8.0, 8.1 and 8.7 respectively and is at least 30 fold selective over a range of
      other receptors. [(35)S]-GTPgammaS binding studies showed that SB-272183 acts as
      a partial agonist at human recombinant 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors
      with intrinsic activities of 0.4, 0.4 and 0.8 respectively, compared to 5-HT. SB
      272183 inhibited 5-HT-induced stimulation of [(35)S]-GTPgammaS binding at human 5
      HT(1A) and 5-HT(1B) receptors to give pA(2) values of 8.2 and 8.5 respectively.
      However, from [(35)S]-GTPgammaS autoradiographic studies in rat and human dorsal
      raphe nucleus, SB-272183 did not display intrinsic activity up to 10 microM but
      did block 5-HT-induced stimulation of [(35)S]-GTPgammaS binding. From
      electrophysiological studies in rat raphe slices in vitro, SB-272183 did not
      effect cell firing rate up to 1 microM but was able to attenuate (+)8-OH-DPAT
      induced inhibition of cell firing to give an apparent pK(b) of 7.1. SB-272183
      potentiated electrically-stimulated [(3)H]-5-HT release from rat and guinea-pig
      cortical slices at 100 and 1000 nM, similar to results previously obtained with
      the 5-HT(1B) and 5-HT(1D) receptor antagonist, GR127935. Fast cyclic voltammetry
      studies in rat dorsal raphe nucleus showed that SB-272183 could block sumatriptan
      induced inhibition of 5-HT efflux, with an apparent pK(b) of 7.2, but did not
      effect basal efflux up to 1 microM. These studies show that, in vitro, SB-272183
      acts as an antagonist at native tissue 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors.

PMID- 11454653
TI  - Role of opioid receptors in neurogenic dural vasodilation and sensitization of
      trigeminal neurones in anaesthetized rats.
AB  - Migraine headache is thought to be caused by a distension of meningeal blood
      vessels, the activation of trigeminal sensory neurones and the the development of
      a central sensitization within the trigeminal nucleus caudalis (TNC). It has been
      proposed that clinically effective 5-HT(1B/1D) agonists act peripherally to
      inhibit the release of calcitonin gene-related peptide (CGRP) and neurogenic
      dural vasodilation, and to attenuate nociceptive neurotransmission within the
      TNC. Since opioids are also effective anti-migraine agents the present studies
      investigated the role of opioids within the trigemino-vascular system in
      anaesthetised rats. Electrical stimulation of the dura mater evoked neurogenic
      dural vasodilation which was significantly inhibited by morphine (1 mg kg(-1))
      the selective mu-opioid agonist DAGO (10 microg kg(-1)) and the mixed
      agonist/antagonist butorphanol (1 mg kg(-1)) but not by the kappa- and delta
      opioid agonists (+/-) U50488H (100 microg kg(-1)) and DPDPE (1 mg kg(-1)).
      Morphine had no effect on CGRP-evoked dural vasodilation. In electrophysiological
      studies morphine (1 - 10 mg kg(-1)) significantly attenuated brainstem neuronal
      activity in response to electrical stimulation of the dura by 65% at 10 mg kg(
      1). Morphine (3 mg kg(-1)) also inhibited the TNC neuronal sensitization
      following CGRP-evoked dilation. The present studies have demonstrated that
      opioids block the nociceptive neurotransmission within the trigeminal nucleus
      caudalis and in addition inhibit neurogenic dural vasodilation via an action on
      mu-opioid receptors located on trigeminal sensory fibres innervating dural blood
      vessels. These peripheral and central actions are similar to those of the
      'triptan' 5-HT(1B/1D) agonists and could account for the anti-migraine actions of
      opioids.

PMID- 11454654
TI  - Endogenous sulphur-containing amino acids: potent agonists at presynaptic
      metabotropic glutamate autoreceptors in the rat central nervous system.
AB  - We have recently demonstrated that presynaptically located metabotropic glutamate
      (mGlu) autoreceptors regulate synaptic glutamate release both in vitro and in
      vivo. We now report a positive modulatory action of the sulphur-containing amino
      acids (SCAAs), L-cysteic acid (CA) and L-cysteine sulphinic acid (CSA), at
      presynaptic group I mGlu receptors, specifically of the mGlu5 subtype, acting to
      enhance synaptic glutamate release from the rat forebrain in vitro. Neuronal
      glutamate release was monitored using electrically-evoked efflux of preloaded
      [(3)H]-D-aspartate from rat forebrain hemisections. Both CA (3 - 100 muM) and CSA
      (1 - 100 microM), in addition to the selective group I mGlu receptor agonist, (S)
      3,5-dihydroxyphenylglycine ((S)-DHPG), concentration-dependently enhanced
      electrically-stimulated efflux of [(3)H]-D-aspartate from the rat forebrain
      slices. Basal efflux of label remained unchanged. The inhibitory activity of the
      broad spectrum mGlu receptor antagonist, (+/-)-alpha-methyl-4
      carboxyphenylglycine ((+/-)-MCPG; 200 microM), coupled with the inactivity of the
      selective mGlu1 receptor antagonists, (R,S)-1-aminoindan-1,5-dicarboxylic acid
      ((R,S)-AIDA; 100 - 500 microM) and the more potent (+)-2-methyl-4
      carboxyphenylglycine (LY367385; 10 microM) against these responses, indicates an
      action of the SCAAs at the mGlu5 receptor subtype. This proposal is supported by
      the potent inhibition of these responses by the selective, non-competitive mGlu5
      receptor antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 10 microM). The
      observed enhancement of the responses to high concentrations of CA by the
      selective mGlu5 receptor desensitization inhibitor, cyclothiazide (CYZ; 10
      microM), is also consistent with this concept. Administration of the agonists in
      the presence of bovine serum albumin (BSA; 5 - 15 mg ml(-1)) markedly attenuated
      the positive modulatory responses observed, strongly supporting a role for
      arachidonic acid in the expression of these mGlu5 receptor-mediated responses.
      The regulatory actions of SCAAs on synaptic glutamate release demonstrated in the
      present study may provide a physiological function for these putative
      neurotransmitter amino acids in the mammalian brain. These central actions of the
      SCAAs may have wide-ranging implications for a range of neurological and
      neuropsychiatric disease states and their treatment.

PMID- 11454655
TI  - Identification of two distinct vasodilator pathways activated by ATP in the
      mesenteric bed of the rat.
AB  - Adenosine 5'-triphosphate (ATP) has important roles in the cardiovascular system,
      modulating vascular tone by acting as both a vasoconstrictor and a vasodilator.
      The dilator function of ATP is traditionally thought to be monophasic and
      mediated primarily by nitric oxide (NO). Here we have identified the endothelium
      dependent biphasic nature of ATP-induced vasodilatation of the rat isolated
      mesenteric bed and investigated the two distinct pathways involved. ATP, at doses
      of 1x10(-11) to 1x10(-8) moles, induced transient relaxations that were inhibited
      by the NO synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME:
      1x10(-4) M), the soluble guanylyl cyclase inhibitor, 1H-[1,2,4]Oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ: 3x10(-6) M) and KCl (6x10(-2) - 1.2x10(-1) M). At doses
      upwards of 1x10(-8) moles (1x10(-8) - 3x10(-7) moles), ATP also induced prolonged
      vasodilatations which were unaltered by L-NAME, L-NAME (1x10(-3) M) and
      indomethacin (1x10(-5) M), or by ODQ, but were abolished in the presence of KCl.
      In addition, the cannabinoid CB(1) receptor antagonist SR141716A (1x10(-5) M) was
      found to inhibit the second prolonged phase of vasodilatation. However, at the
      concentration used SR141716A is reported to be non-selective. A second CB(1)
      receptor antagonist, AM251 (1x10(-6) M), had a small but significant inhibitory
      effect on the second phase of ATP-induced vasodilatation. SR141716A, AM251 and
      KCl (6x10(-2) - 1.2x10(-1) M) all inhibited anandamide-induced relaxation of the
      isolated mesenteric bed. These observations demonstrate that ATP stimulates
      vasodilatation of the mesenteric bed by two distinct mechanisms involving the
      release of NO and an EDHF. In the absence of better pharmacological tools we can
      only speculate as to the involvement of an endogenous CB(1) receptor ligand in
      these responses.

PMID- 11454656
TI  - Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by
      adenosine analogues.
AB  - Although adenosine analogues such as 5'-N-ethylcarboxamidoadenosine (NECA) relax
      the rat thoracic aorta in a partially endothelium-dependent manner via adenosine
      A(2A) receptors, others such as N(6)-R-phenylisopropyladenosine (R-PIA) act via
      an endothelium-independent, antagonist-insensitive mechanism. The role of cyclic
      nucleotides in these relaxations was investigated in isolated aortic rings using
      inhibitors of adenylate and guanylate cyclases as well as subtype-selective
      phosphodiesterase inhibitors. The adenylate cyclase inhibitor 9-(tetrahydro-2
      furanyl)-9H-purin-6-amine (SQ 22536; 100 microM) significantly inhibited
      responses to NECA, but not responses to R-PIA. The type IV (cyclic AMP-selective)
      phosphodiesterase inhibitor 4-[(3-butoxy-4-methoxyphenyl)methyl]-2
      imidazolidinone (RO 20-1724; 30 microM) significantly enhanced responses to NECA
      and to a lesser extent those to R-PIA. The guanylate cyclase inhibitor 1H
      [1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ; 100 microM) significantly inhibited
      responses to NECA and acetylcholine but not responses to R-PIA. The selective
      phosphodiesterase V (cyclic GMP-selective) inhibitors, zaprinast (10 microM) and
      4-[[3',4'-(methylenedioxy)benzyl]amino]-6-methoxyquinazoline (MMQ; 1 microM), had
      no significant effect on responses to either NECA or R-PIA, but enhanced
      responses to acetylcholine. These results are consistent with the effects of NECA
      being via activation of endothelial receptors to release NO which stimulates
      guanylate cyclase, as well as smooth muscle receptors coupled to stimulation of
      adenylate cyclase. The lack of effect of zaprinast and MMQ on responses to NECA
      are likely to be due to simultaneous activation of both adenylate and guanylate
      cyclases in the smooth muscle, as cyclic AMP reduces the sensitivity of
      phosphodiesterase V to inhibitors. These results also suggest that the effects of
      R-PIA are via neither of these mechanisms.

PMID- 11454657
TI  - Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an
      in vitro reperfusion model.
AB  - We examined the effect of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine
      (ibudilast), which has been clinically used for bronchial asthma and
      cerebrovascular disorders, on cell viability induced in a model of reperfusion
      injury. Ibudilast at 10 - 100 microM significantly attenuated the H(2)O(2)
      induced decrease in cell viability. Ibudilast inhibited the H(2)O(2)-induced
      cytochrome c release, caspase-3 activation, DNA ladder formation and nuclear
      condensation, suggesting its anti-apoptotic effect. Phosphodiesterase inhibitors
      such as theophylline, pentoxyfylline, vinpocetine, dipyridamole and zaprinast,
      which increased the guanosine-3',5'-cyclic monophosphate (cyclic GMP) level, and
      dibutyryl cyclic GMP attenuated the H(2)O(2)-induced injury in astrocytes.
      Ibudilast increased the cyclic GMP level in astrocytes. The cyclic GMP-dependent
      protein kinase inhibitor KT5823 blocked the protective effects of ibudilast and
      dipyridamole on the H(2)O(2)-induced decrease in cell viability, while the cyclic
      AMP-dependent protein kinase inhibitor KT5720, the cyclic AMP antagonist Rp
      cyclic AMPS, the mitogen-activated protein/extracellular signal-regulated kinase
      inhibitor PD98059 and the leukotriene D(4) antagonist LY 171883 did not. KT5823
      also blocked the effect of ibudilast on the H(2)O(2)-induced cytochrome c release
      and caspase-3-like protease activation. These findings suggest that ibudilast
      prevents the H(2)O(2)-induced delayed apoptosis of astrocytes via a cyclic GMP,
      but not cyclic AMP, signalling pathway.

PMID- 11454658
TI  - Pharmacological evidence for the activation of potassium channels as the
      mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat
      small resistance arteries.
AB  - The hypotensive and vasorelaxant effect of dioclein in resistance mesenteric
      arteries was studied in intact animals and isolated vessels, respectively. In
      intact animals, initial bolus administration of dioclein (2.5 mg kg(-1)) produced
      transient hypotension accompanied by an increase in heart rate. Subsequent doses
      of dioclein (5 and 10 mg kg(-1)) produced hypotensive responses with no
      significant change in heart rate. N(G)-nitro-L-arginine methyl ester (L-NAME) did
      not affect the hypotensive response. In endothelium-containing or -denuded
      vessels pre-contracted with phenylephrine, dioclein (5 and 10 mg kg(-1) produced
      a concentration-dependent vasorelaxation (IC(50)=0.3+/-0.06 and 1.6+/-0.6 microM,
      respectively) which was not changed by 10 microM indomethacin. L-NAME (300
      microM) produced a shift to the right. Dioclein was without effect on contraction
      of vessels induced by physiological salt solution (PSS) containing 50 mM KCl and
      the concentration dependence of dioclein's effect on phenylephrine induced
      contraction was shifted to the right in vessels bathed in PSS containing 25 mM
      KCl. Tetraethylammonium (10 mM) and BaCl(2) (1 mM) increased the IC(50) for
      dioclein-induced vasorelaxation without affecting the maximal response (E(max)).
      Charybdotoxin (100 nM), 4-aminopyridine (1 mM) and iberiotoxin (100 nM) increased
      the IC(50) and reduced the E(max). Apamin (1 microM) reduced the E(max) without
      affecting the IC(50). Dioclein produced a hyperpolarization in smooth muscle of
      mesenteric arteries with or without endothelium (7.7+/-1.4 mV and 12.3+/-3.6 mV,
      respectively). In conclusion dioclein lowered arterial pressure probably through
      a decrease in peripheral vascular resistance. The underling mechanism implicated
      in the vasorelaxant effect of dioclein appears to be the opening of K(Ca) and Kv
      channels and subsequent membrane hyperpolarization.

PMID- 11454659
TI  - Role of the extracellular signal-regulated kinase (Erk) signal transduction
      cascade in alpha(2) adrenoceptor-mediated vasoconstriction in porcine palmar
      lateral vein.
AB  - The mechanism of alpha(2) adrenoceptor-mediated vasoconstriction is unknown, but
      may involve activation of voltage-sensitive calcium channels, and/or a protein
      tyrosine kinase. Recently the extracellular signal-regulated kinase (Erk)
      cascade, often an event downstream of tyrosine kinase activation, has been shown
      to mediate vasoconstriction to a variety of agents. The aim of this present study
      was to determine the involvement of the Erk signal transduction cascade in
      alpha(2) adrenoceptor-mediated vasoconstriction, and to confirm the involvement
      of activation of voltage-sensitive calcium channels, and protein tyrosine kinase.
      Contractions to the alpha(2) adrenoceptor agonist UK14304 in the porcine palmar
      lateral vein in vitro were reduced 70 - 80% by the MEK inhibitors PD98059 (10 -
      50 microM) and U0126 (10 - 50 microM), indicating the involvement of the Erk
      signal transduction cascade. Immunoblots also demonstrated an increase in the
      phosphorylated (activated) form of Erk in palmar lateral vein segments after
      contraction with UK14304, which was inhibited by PD98059 and U0126. The calcium
      channel blockers nifedipine and verapamil, or removal of extracellular calcium
      inhibited UK14304-induced contractions and phosphorylation of Erk, demonstrating
      the importance of an influx of extracellular calcium. UK14304-induced
      contractions were inhibited by PP2 (1 - 10 microM), a selective inhibitor of Src
      tyrosine kinases, but not by PP3, an inactive analogue. PP2 also prevented the
      phosphorylation of Erk by UK14304. These data demonstrate that alpha(2)
      adrenoceptor-mediated vasoconstriction in the porcine palmar lateral vein is
      dependent upon activation of the Erk signal transduction cascade, which is
      downstream of an influx of extracellular calcium, and activation of Src tyrosine
      kinases.

PMID- 11454660
TI  - A microdialysis study of the novel antiepileptic drug levetiracetam:
      extracellular pharmacokinetics and effect on taurine in rat brain.
AB  - Using a rat model which allows serial blood sampling and concurrent brain
      microdialysis sampling, we have investigated the temporal kinetic inter
      relationship of levetiracetam in serum and brain extracellular fluid (frontal
      cortex and hippocampus) following systemic administration of levetiracetam, a new
      antiepileptic drug. Concurrent extracellular amino acid concentrations were also
      determined. After administration (40 or 80 mg kg(-1)), levetiracetam rapidly
      appeared in both serum (T(max), 0.4 - 0.7 h) and extracellular fluid (T(max), 2.0
      - 2.5 h) and concentrations rose linearly and dose-dependently, suggesting that
      transport across the blood-brain barrier is rapid and not rate-limiting. The
      serum free fraction (free/total serum concentration ratio; mean+/-s.e.mean range
      0.93 - 1.05) was independent of concentration and confirms that levetiracetam is
      not bound to blood proteins. The kinetic profiles for the hippocampus and frontal
      cortex were indistinguishable suggesting that levetiracetam distribution in the
      brain is not brain region specific. However, t(1/2) values were significantly
      larger than those for serum (mean range, 3.0 - 3.3 h vs 2.1 - 2.3 h) and
      concentrations did not attain equilibrium with respect to serum. Levetiracetam
      (80 mg kg(-1)) was associated with a significant reduction in taurine in the
      hippocampus and frontal cortex. Other amino acids were unaffected by
      levetiracetam. Levetiracetam readily and rapidly enters the brain without
      regional specificity. Its prolonged efflux from and slow equilibration within the
      brain may explain, in part, its long duration of action. The concurrent changes
      in taurine may contribute to its mechanism of action.

PMID- 11454661
TI  - Sirolimus, but not the structurally related RAD (everolimus), enhances the
      negative effects of cyclosporine on mitochondrial metabolism in the rat brain.
AB  - Clinical studies have shown enhancement of cyclosporine toxicity when co
      administered with the immunosuppressant sirolimus. We evaluated the biochemical
      mechanisms underlying the sirolimus/cyclosporine interaction on rat brain
      metabolism using magnetic resonance spectroscopy (MRS) and compared the effects
      of sirolimus with those of the structurally related RAD. Two-week-old rats (25 g)
      were allocated to the following treatment groups (all n=6): I. control, II.
      cyclosporine (10 mg kg(-1) d(-1)), III. sirolimus (3 mg kg(-1) d(-1)), IV. RAD (3
      mg kg(-1) d(-1)), V. cyclosporine+sirolimus and VI. cyclosporine+RAD. Drugs were
      administered by oral gavage for 6 days. Twelve hours after the last dose,
      metabolic changes were assessed in brain tissue extracts using multinuclear MRS.
      Cyclosporine significantly inhibited mitochondrial glucose metabolism (glutamate:
      78+/-6% of control; GABA: 67+/-12%; NAD(+): 76+/-3%; P<0.05), but increased
      lactate production. Sirolimus and RAD inhibited cytosolic glucose metabolism via
      lactate production (sirolimus: 81+/-3% of control, RAD: 69+/-2%; P<0.02).
      Sirolimus enhanced cyclosporine-induced inhibition of mitochondrial glucose
      metabolism (glutamate: 60+/-4%; GABA: 59+/-8%; NAD(+): 45+/-5%; P<0.02 versus
      cyclosporine alone). Lactate production was significantly reduced. In contrast,
      RAD antagonized the effects of cyclosporine (glutamate, GABA, and NAD(+), not
      significantly different from controls). The results can partially be explained by
      pharmacokinetic interactions: co-administration increased the distribution of
      cyclosporine and sirolimus into brain tissue, while co-administration with RAD
      decreased cyclosporine brain tissue concentrations. In addition RAD, but not
      sirolimus, distributed into brain mitochondria. The combination of
      cyclosporine/RAD compares favourably to cyclosporine/sirolimus in regards to
      their effects on brain high-energy metabolism and tissue distribution in the rat.

PMID- 11454662
TI  - Augmented acetylcholine-induced translocation of RhoA in bronchial smooth muscle
      from antigen-induced airway hyperresponsive rats.
AB  - Acetylcholine (ACh)-induced translocation of RhoA in bronchial smooth muscle of
      repeatedly antigen-challenged rats that have a marked airway hyperresponsiveness
      (AHR) was examined. ACh induced time- and concentration-dependent translocation
      of RhoA to the plasma membrane, indicating an activation of RhoA in bronchial
      smooth muscle. The level of ACh-induced RhoA translocation was further increased
      markedly in the AHR group as compared to that in the control group. It is
      suggested that the augmented activation of RhoA observed in the hyperresponsive
      bronchial smooth muscle might be responsible for the enhanced ACh-induced Ca(2+)
      sensitization of bronchial smooth muscle contraction associated with AHR.

PMID- 11454663
TI  - Molecular cloning, pharmacological properties and tissue distribution of the
      porcine 5-HT(1B) receptor.
AB  - Using a combination of RT - PCR and inverse-PCR techniques, we amplified, cloned
      and sequenced a full-length porcine 5-HT(1B) receptor cDNA derived from porcine
      cerebral cortex. Sequence analysis revealed 1170 bp encoding an open reading
      frame of 390 amino acids showing a 95% similarity with the human 5-HT(1B)
      receptor. The recombinant porcine 5-HT(1B) cDNA was expressed in monkey Cos-7
      cells and its pharmacological profile was determined by radioligand binding assay
      using [(3)H]-GR125743. The affinities of several agonists (L694247>ergotamine >
      or =5-carboxamidotryptamine=dihydroergotamine=5
      HT>CP122638=zolmitriptan>sumatriptan) and putative antagonists
      (GR127935>methiothepin>SB224289>>ritanserin>ketanserin > or =BRL15572) correlated
      highly with those described for the recombinant human 5-HT(1B) receptor. In
      membranes obtained from cells co-expressing the porcine 5-HT(1B) receptor and a
      mutant G(alphao)Cys(351)Ile protein, 5-HT and zolmitriptan increased, while the 5
      HT(1B) receptor antagonist SB224289 decreased basal [(35)S]-GTPgammaS binding,
      thus showing inverse agonism. The potency of zolmitriptan in the [(35)S]
      GTPgammaS binding assay (pEC(50): 7.64+/-0.04) agreed with its affinity in
      displacing the antagonist [(3)H]-GR125743 (pK(i): 7.36+/-0.07). The 5-HT(1B)
      receptor mRNA was observed by RT-PCR in several blood vessels, cerebral cortex,
      cerebellum and trigeminal ganglion. In situ hybridization performed in frontal
      cerebral cortex sections revealed the expression of 5-HT(1B) receptor mRNA in
      pyramidal cells. In conclusion, we have cloned and established the amino acid
      sequence, ligand binding profile and location of the porcine 5-HT(1B) receptor.
      This information may be useful in exploring the role of 5-HT(1B) receptor in
      pathophysiological processes relevant for novel drug discovery in diseases such
      as migraine.

PMID- 11454664
TI  - Endothelium-derived hyperpolarizing factor and potassium use different mechanisms
      to induce relaxation of human subcutaneous resistance arteries.
AB  - This investigation examined the hypothesis that release of K(+) accounts for EDHF
      activity by comparing relaxant responses produced by ACh and KCl in human
      subcutaneous resistance arteries. Resistance arteries (internal diameter 244+/-12
      microm, n=48) from human subcutaneous fat biopsies were suspended in a wire
      myograph. Cumulative concentration-response curves were obtained for ACh (10(-9) 
      3x10(-5) M) and KCl (2.5 - 25 mM) following contraction with noradrenaline (NA;
      0.1 - 3 microM). ACh (E(max) 99.07+/-9.61%; -LogIC(50) 7.03+/-0.22; n=9) and KCl
      (E(max) 74.14+/-5.61%; -LogIC(50) 2.12+/-0.07; n=10)-induced relaxations were
      attenuated (P<0.0001) by removal of the endothelium (E(max) 8.21+/-5.39% and
      11.56+/-8.49%, respectively; n=6 - 7). Indomethacin (10 microM) did not alter ACh
      induced relaxation whereas L-NOARG (100 microM) reduced this response (E(max)
      61.7+/-3.4%, P<0.0001; n=6). The combination of ChTx (50 nM) and apamin (30 nM)
      attenuated the L-NOARG-insensitive component of ACh-induced relaxation (E(max):
      15.2+/-10.5%, P<0.002, n=6) although these arteries retained the ability to relax
      in response to 100 microM SIN-1 (E(max) 127.6+/-13.0%, n=3). Exposure to BaCl(2)
      (30 microM) and Ouabain (1 mM) did not attenuate the L-NOARG resistant component
      of ACh-mediated relaxation (E(max), 76.09+/-8.92, P=0.16; n=5). KCl-mediated
      relaxation was unaffected by L-NOARG+indomethacin (E(max); 68.1+/-5.6%, P=0.33;
      n=5) or the combination of L-NOARG/indomethacin/ChTx/apamin (E(max); 86.61+/
      14.02%, P=0.35; n=6). In contrast, the combination of L-NOARG, indomethacin,
      ouabain and BaCl(2) abolished this response (E(max), 5.67+/-2.59%, P<0.0001,
      n=6). The characteristics of KCl-mediated relaxation differed from those of the
      nitric oxide/prostaglandin-independent component of the response to ACh, and were
      endothelium-dependent, indicating that K(+) does not act as an EDHF in human
      subcutaneous resistance arteries.

PMID- 11454665
TI  - Inhibition of poly (ADP-ribose) synthetase by gene disruption or inhibition with
      5-iodo-6-amino-1,2-benzopyrone protects mice from multiple-low-dose
      streptozotocin-induced diabetes.
AB  - Activation of poly(ADP-ribose) synthetase (PARS, also termed polyADP-ribose
      polymerase or PARP) has been proposed as a major mechanism contributing to beta
      cell destruction in type I diabetes. In the present study, we have investigated
      the role of PARS in mediating the induction of diabetes and beta-cell death in
      the multiple-low-dose-streptozotocin (MLDS) model of type I diabetes. Mice
      genetically deficient in PARS were found to be less sensitive to MLDS than wild
      type mice, with a lower incidence of diabetes and reduced hyperglycemia. A potent
      inhibitor of PARS, 5-iodo-6-amino-1,2-benzopyrone (INH(2)BP), was also found to
      protect mice from MLDS and prevent beta-cell loss, in a dose-dependent manner.
      Paradoxically, in the PARS deficient mice, the compound increased the onset of
      diabetes. In vitro the cytokine combination; interleukin-1beta, tumor necrosis
      factor-alpha and interferon-gamma inhibited glucose-stimulated insulin secretion
      from isolated rat islets of Langerhans and decreased RIN-5F cell viability. The
      PARS inhibitor, INH(2)BP, protected both the rat islets and the beta-cell line,
      RIN-5F, from these cytokine-mediated effects. These protective effects were not
      mediated by inhibition of cytokine-induced nitric oxide formation. Inhibition of
      PARS by INH(2)BP was unable to protect rat islet cells from cytokine-mediated
      apoptosis. Cytokines, peroxynitrite and streptozotocin were all shown to induce
      PARS activation in RIN-5F cells, an effect suppressed by INH(2)BP. The present
      study provides evidence for in vivo PARS activation contributing to beta-cell
      damage and death in the MLDS model of diabetes, and indicates a role for PARS
      activation in cytokine-mediated depression of insulin secretion and cell
      viability in vitro.

PMID- 11454666
TI  - Modulation of haem oxygenase-1 expression by nitric oxide and leukotrienes in
      zymosan-activated macrophages.
AB  - Phagocytosis of unopsonized zymosan by RAW 264.7 macrophages upregulated protein
      expression of haem oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS) and
      cyclo-oxygenase-2 (COX-2) in a time- and concentration-dependent manner. In the
      presence of zymosan, exogenous prostaglandin E(2) (PGE(2)) did not exert
      significant effects on the expression of these three enzymes. In contrast,
      exogenous leukotriene B(4) (LTB(4)) and LTC(4) in the nanomolar range inhibited
      HO-1 and iNOS expression, as well as nitrite accumulation. The COX inhibitors
      indomethacin and NS398 weakly inhibited HO-1 expression but had no effect on iNOS
      and COX-2 expression or nitrite. In contrast, the 5-lipoxygenase (5-LO) inhibitor
      ZM 230,487 significantly decreased HO-1, iNOS and nitrite, which were not
      affected by zileuton. Dexamethasone showed an inhibitory effect on HO-1
      expression induced by zymosan. ZM 230,487 but not zileuton, inhibited the shift
      due to nuclear factor-kappaB (NF-kappaB), whereas they did not modify activator
      protein-1 (AP-1) binding. Our results suggest that inhibition of NF-kappaB
      binding could mediate the effects of ZM 230,487 on the modulation of HO-1 and
      iNOS protein expression. NOS inhibition by L-N(G)-nitroarginine methyl ester (L
      NAME) or 1400 W abolished nitrite production and strongly reduced HO-1
      expression. These results show an induction of HO-1 protein expression by zymosan
      phagocytosis in macrophages, with a positive modulatory role for endogenous NO
      and a negative regulation by exogenous LTs, likely dependent on the reduction of
      iNOS expression and NO production.

PMID- 11454667
TI  - Evidence that ET-1, but not ET-3 and S6b, ET(A)-receptor mediated contractions in
      isolated rat mesenteric arteries are modulated by co-activation of ET(B)
      receptors.
AB  - The effects of agonists with endothelin (ET) ET(A)-receptor activity have been
      analysed in relation to their interaction with ET(B) receptors in rat mesenteric
      arteries. ET-1, sarafotoxin 6b (S6b) and ET-3 induced large, slow-onset and
      sustained contractions whereas S6c induced weak transient contractions. However,
      following pre-contraction with U46619 and subsequent relaxation with forskolin,
      the effect of S6c was amplified, indicating a potential for powerful ET(B)
      receptor mediated contraction. The selective ET(A)-receptor antagonist, FR139317,
      produced parallel rightward shifts of ET-1, S6b and ET-3 concentration-effect
      curves indicating that the contractions were mediated by ET(A) receptors.
      However, the corresponding FR139317 pK(B) values were significantly different
      between the agonists. As expected FR139317 had no effect on S6c responses. Pre
      treatment with S6c to desensitize ET(B) receptors, increased ET-1 potency and the
      pK(B) value for FR139317. In contrast, neither the potency of S6b and ET-3 nor
      the pK(B) values for FR139317 estimated using these agonists were affected by
      ET(B)-receptor desensitization. Segments pre-contracted with submaximal
      concentrations of S6b and ET-3, but not ET-1, rapidly relaxed following wash-out
      or FR139317 administration. The results indicate that the small contractile
      response to selective ET(B) receptor activation, barely detectable under standard
      bioassay conditions, is greatly amplified when adenylate cyclase activity is
      elevated. Moreover, the response to ET(A) receptor activation by ET-1, but not ET
      3 and S6b, is significantly modified by co-activation of ET(B) receptors. This
      interaction has a significant effect on the apparent affinity of ET(A)-receptor
      selective antagonists when ET-1 is used as agonist and decreases the potency of
      ET-1.

PMID- 11454669
TI  - Frequent loss of estrogen receptor-beta expression in prostate cancer.
AB  - The role of estrogen and its receptors in the etiology and progression of
      prostate cancer (PC) is poorly understood. In normal and malignant human
      prostate, estrogen receptor-alpha is expressed only in the stroma, whereas
      estrogen receptor-beta (ERbeta) is present in both normal stroma and epithelium.
      Because loss of ERbeta expression is associated with prostate hyperplasia in
      ERbeta-null mice, this study determined patterns of ERbeta expression in normal,
      hyperplastic, and malignant human prostate and associations with clinical
      outcome. Five normal prostates from organ donors and 159 radical prostatectomy
      specimens from patients with clinically localized PC were assessed for ERbeta
      expression using immunohistochemistry. ERbeta-positivity was defined as > or =5%
      of cells demonstrating nuclear immunoreactivity. All of the five normal prostates
      showed strong ERbeta-nuclear staining in >95% of the epithelium and 35% of the
      stromal cells. The number of ERbeta-positive cases declined to 24.2% (38/157) in
      hyperplasia adjacent to carcinoma and 11.3% (18/159) in PCs. ERbeta-positivity
      was related to decreased relapse-free survival (log-rank P = 0.04). Thus, loss of
      ERbeta expression is associated with progression from normal prostate epithelium
      to PC, whereas those cancers that retained ERbeta expression were associated with
      a higher rate of recurrence. These data identify the need to further investigate
      the potential role of ERbeta in the regulation of prostate epithelial cell
      proliferation and the functional consequences of decreased ERbeta expression in
      the evolution of PC.

PMID- 11454668
TI  - Characterization of ionotropic glutamate receptors in human lymphocytes.
AB  - The effect of L-glutamate (Glu) on human lymphocyte function was studied by
      measuring anti-CD(3) monoclonal antibody (mAb) or phytohaemagglutinin (PHA)
      induced intracellular Ca(2+) ([Ca(2+)](i)) rise (Fura-2 method), and cell
      proliferation (MTT assay). Glu (0.001 - 100 microM) did not modify basal
      lymphocyte [Ca(2+)](i), but significantly potentiated the effects of anti-CD(3)
      mAb or PHA. Maximal [Ca(2+)](i) rises over resting cells were: 165+/-8 and 247+/
      10 nM at 3.0x10(-2) mg ml(-1) anti-CD(3) mAb; 201+/-4 and 266+/-9 nM at 5.0x10(
      2) mg ml(-1) PHA, in the absence or presence of 1 microM Glu, respectively. The
      Glu effect showed a bell-shape concentration-dependent relationship, with a
      maximum (+90+/-3% for anti-CD(3) mAb and +57+/-2% for PHA over Glu-untreated
      cells) at 1 microM. Non-NMDA receptor agonists (1 microM) showed a greater
      efficacy (+76+/-2% for (S)-AMPA; +78+/-4% for KA), if compared to NMDA (+46+/
      2%), or Glu itself. Ionotropic Glu receptor antagonists completely inhibited the
      effects of the corresponding specific receptor agonists (1 microM). The IC(50)
      values calculated were: 0.9 microM for D-AP5; 0.6 microM for (+)-MK801; 0.3
      microM for NBQX. Both NBQX and KYNA were able to abolish Glu effect. The IC(50s)
      calculated were: 3.4 microM for NBQX; 0.4 microM for KYNA. Glu (0.1 - 1 mM) did
      not change the resting cell proliferation, whereas Glu (1 mM) significant
      inhibited (-27+/-4%) PHA (1.0x10(-2) mg ml(-1))-induced lymphocyte proliferation
      at 72 h. In conclusion, human lymphocytes express ionotropic Glu receptors
      functionally operating as modulators of cell activation.

PMID- 11454670
TI  - Comparative analyses of transgene delivery and expression in tumors inoculated
      with a replication-conditional or -defective viral vector.
AB  - Viral vectors for cancer can be classified into those that do not replicate
      (replication-defective vectors) and those that selectively replicate in
      neoplastic cells (replication-conditional or oncolytic vectors). Both of these
      can deliver anticancer cDNAs for therapeutic purposes. Opposite hypotheses can be
      made regarding the advantages of each vector type with regard to anatomic
      transgene expression. For the former vector, because cDNA delivery occurs in
      neoplastic cells that have the ability to migrate into the tumor mass, relatively
      extensive anatomic and temporal expression of anticancer functions may occur. For
      the latter vector, active viral replication may permit anatomically and
      temporally extensive delivery of the foreign cDNA into the tumor mass. Herein, we
      performed a simple comparative analysis to test which of these hypotheses is
      valid. Direct inoculation of s.c. tumors with a replication-conditional or a
      replication-defective viral vector, each of which expressed lacZ cDNA, was
      performed. Tumors were excised and analyzed for anatomic delivery of beta
      galactosidase and for neoplastic viral titers. We find that lacZ cDNA expression
      is observed in approximately 40% of the tumor area 3, 7, and 14 days after
      injection with the replication-conditional vector, whereas approximately 10% of
      the tumor area expresses the transgene 3 days after injection with the
      replication-defective vector, with a rapid decline in expression thereafter.
      Titers of the replication-conditional virus remain stable within injected tumors
      for the 14 days of the assay (approximately 1:1,000 of the initial injection
      dose), whereas titers of the replication-defective vector decrease rapidly after
      injection (to a value of 1:100,000 of the initial injection dose). Taken in
      conjunction, these studies show that transgene delivery and expression in tumors
      last longer and are found throughout an anatomically more extensive area after
      injection with replication-conditional gene therapy vectors than after injection
      with replication-defective gene therapy vectors.

PMID- 11454671
TI  - Amplification of urokinase gene in prostate cancer.
AB  - Prostate cancer is the most common male malignancy in the United States as well
      as in many European countries. It is curable as long as it is localized, but the
      invasion of prostate cancer and formation of metastasis turn it into a life
      threatening disease. Urokinase-type plasminogen activator (uPA) is believed to
      play a key role in tissue degradation and cell migration under various normal and
      pathological conditions, including cancer invasion and metastasis. Increased
      expression of uPA has been reported in various malignancies including prostate
      cancer. However, the mechanisms of the overexpression have remained poorly
      understood. Here, we report increased copy number of uPA gene in 3 of 13 hormone
      refractory prostate carcinomas, including 1 high-level amplification. Real-time
      quantitative reverse transcription-PCR showed that the increased expression of
      uPA coincided with the amplification of the gene in these tumors. Matrigel
      invasion assay showed that prostate cancer cell line PC-3, containing
      amplification of the uPA gene, was more sensitive to the urokinase inhibitor,
      amiloride, than DU145 or LNCaP cell lines, which do not have the amplification.
      The findings suggest that one of the mechanisms underlying the overexpression of
      the uPA is the amplification of the gene, which is associated with the increased
      invasive potential of the cells.

PMID- 11454672
TI  - Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic
      breast cancer.
AB  - Amplification of the HER-2/neu oncogene and amplification of the topoisomerase
      IIalpha gene are important determinators of the response to chemotherapy in
      advanced breast cancer. Assays of these genes are usually carried out using
      primary tumor samples, because biopsies from metastatic lesions are not usually
      taken. We studied the concordance of Her-2/neu and topoisomerase IIalpha
      amplification in primary breast tumors and their metastases by immunostaining and
      DNA in situ hybridization. HER-2/neu amplification, present in 28% of the primary
      tumors (n = 46), was always associated with amplification in its metastasis.
      Conversely, no metastases with HER-2/neu amplification were seen without
      amplification in the primary tumor. Topoisomerase IIalpha gene copy status
      (amplification/deletion/unaltered) remained generally unchanged in HER-2/neu
      positive tumors, but in three cases, the predominant cell population in
      metastatic tissue was present only as a subpopulation in the primary tumor. We
      conclude that amplification of HER-2/neu measured in primary tumor reflects the
      status of metastases. Minor discrepancies between primary and metastatic tumors
      in topoisomerase IIalpha gene copy status may reflect evolvement of the amplicon
      structure in successive cell divisions.

PMID- 11454673
TI  - Growth suppression of intracranial xenografted glioblastomas overexpressing
      mutant epidermal growth factor receptors by systemic administration of monoclonal
      antibody (mAb) 806, a novel monoclonal antibody directed to the receptor.
AB  - A mutant epidermal growth factor receptor (variously called DeltaEGFR, de2-7
      EGFR, or EGFRvIII) containing a deletion of 267 amino acids of the extracellular
      domain is frequently highly expressed in human malignant gliomas and has been
      reported for cancers of the lung, breast, and prostate. We tested the efficacy of
      a novel monoclonal anti-DeltaEGFR antibody, mAb 806, on the growth of
      intracranial xenografted gliomas in nude mice. Systemic treatment with mAb 806
      significantly reduced the volume of tumors and increased the survival of mice
      bearing xenografts of U87 MG.DeltaEGFR, LN-Z308.DeltaEGFR, or A1207.DeltaEGFR
      gliomas, each of which expresses high levels of DeltaEGFR. In contrast, mAb 806
      treatment was ineffective with mice bearing the parental U87 MG tumors, which
      expressed low levels of endogenous wild-type EGFR, or U87 MG.DK tumors, which
      expressed high levels of kinase-deficient DeltaEGFR. A slight increase of
      survival of mice xenografted with a wild-type EGFR-overexpressing U87 MG glioma
      (U87 MG.wtEGFR) was effected by mAb 806 concordant with its weak cross-reactivity
      with such cells. Treatment of U87 MG.DeltaEGFR tumors in mice with mAb 806 caused
      decreases in both tumor growth and angiogenesis, as well as increased apoptosis.
      Mechanistically, in vivo mAb 806 treatment resulted in reduced phosphorylation of
      the constitutively active DeltaEGFR and caused down-regulated expression of the
      apoptotic protector, Bcl-XL. These data provide preclinical evidence that mAb 806
      treatment may be a useful biotherapeutic agent for those aggressive gliomas that
      express DeltaEGFR.

PMID- 11454674
TI  - Monoclonal antibody 806 inhibits the growth of tumor xenografts expressing either
      the de2-7 or amplified epidermal growth factor receptor (EGFR) but not wild-type
      EGFR.
AB  - The monoclonal antibody (mAb) 806 was raised against the delta2-7 epidermal
      growth factor receptor (de2-7 EGFR or EGFRvIII), a truncated version of the EGFR
      commonly expressed in glioma. Unexpectedly, mAb 806 also bound the EGFR expressed
      by cells exhibiting amplification of the EGFR gene but not to cells or normal
      tissue expressing the wild-type receptor in the absence of gene amplification.
      The unique specificity of mAb 806 offers an advantage over current EGFR
      antibodies, which all display significant binding to the liver and skin in
      humans. Therefore, we examined the antitumor activity of mAb 806 against human
      tumor xenografts grown in nude mice. The growth of U87 MG xenografts, a glioma
      cell line that endogenously expresses approximately 10(5) EGFRs in the absence of
      gene amplification, was not inhibited by mAb 806. In contrast, mAb 806
      significantly inhibited the growth of U87 MG xenografts transfected with the de2
      7 EGFR in a dose-dependent manner using both preventative and established tumor
      models. Significantly, U87 MG cells transfected with the wild-type EGFR, which
      increased expression to approximately 10(6) EGFRs/cell and mimics the situation
      of gene amplification, were also inhibited by mAb 806 when grown as xenografts in
      nude mice. Xenografts treated with mAb 806 all displayed large areas of necrosis
      that were absent in control tumors. This reduced xenograft viability was not
      mediated by receptor down-regulation or clonal selection because levels of
      antigen expression were similar in control and treated groups. The antitumor
      effect of mAb 806 was not restricted to U87 MG cells because the antibody
      inhibited the growth of new and established A431 xenografts, a cell line
      expressing >10(6) EGFRs/cell. This study demonstrates that mAb 806 possesses
      significant antitumor activity.

PMID- 11454675
TI  - Reduced expression and impaired kinase activity of a Chk2 mutant identified in
      human lung cancer.
AB  - The checkpoint kinase Chk2 is phosphorylated and activated in response to DNA
      damage such as ionizing radiation. Recently, we found a somatic mutation of CHK2
      with clear loss of the wild-type allele in human lung cancer. Here we show that
      the mutant Chk2 exhibits modestly reduced in vitro kinase activity compared with
      wild type, whereas it is normally phosphorylated and activated after ionizing
      radiation. Interestingly, this mutant Chk2 protein was found to be less stable
      than wild type and could be expressed in various cell types only at a
      significantly reduced (20%) level of wild type. These findings confirm that the
      DNA damage checkpoint pathway involving CHK2 is indeed inactivated in this fatal
      adult cancer and also suggest that reduced expression of Chk2 may also be an
      important inactivating mechanism, contributing to the development of lung cancer.

PMID- 11454676
TI  - DNA polymerase kappa, implicated in spontaneous and DNA damage-induced
      mutagenesis, is overexpressed in lung cancer.
AB  - DNA polymerase kappa (Pol kappa) is a newly identified low-fidelity polymerase
      implicated in spontaneous and DNA damage-induced mutagenesis. As an initial study
      to investigate its possible involvement in tumorigenesis, we compared the
      expression level of Pol kappa in tumors and adjacent nontumorous tissues by
      Northern blot, semiquantitative RT-PCR, and Western blot analyses. In this study,
      paired tumor and normal specimens from 29 patients with stages I to IIIb non
      small cell lung cancer (NSCLC), including 13 adenocarcinomas, 15 squamous cell
      cancers, and 1 adenosquamous carcinoma, were analyzed, among which different
      levels of tumor-associated Pol kappa overexpression were observed in 21 of 29
      matched specimens. In addition, five matched specimens exhibited elevated Pol
      kappa expression in both tumor and control tissues, whereas only one nontumorous
      tissue expressed a higher level of Pol kappa than its tumor counterpart. The
      preferential up-regulation of Pol kappa expression in tumors was highly
      significant (P < 0.001). There was no apparent correlation of Pol kappa
      expression levels with tumor histology, grade, and stage or with smoking history.
      Southern blot analysis did not show amplification of the Pol kappa gene,
      indicating that the elevated Pol kappa expression is likely attributable to
      dysregulated transcription. Our data suggest that Pol kappa may contribute to
      lung tumor development by accelerating the accumulation of mutations.

PMID- 11454677
TI  - Cloning and characterization of a human polyamine oxidase that is inducible by
      polyamine analogue exposure.
AB  - Mammalian polyamine catabolism is under the control of two enzymes,
      spermidine/spermine N1-acetyltransferase and the flavin adenine dinucleotide
      dependent polyamine oxidase (PAO). In this study, the cloning and initial
      characterization of human PAO is reported. A 1894-bp cDNA with an open reading
      frame of 1668-bp codes for a protein of 555 amino acids. In vitro
      transcription/translation of this cDNA clone produces the expected M(r) 61,900
      protein with PAO activity. The PAO activity of this clone is inhibited by MDL
      72,527, a specific inhibitor of mammalian PAO. However, neither pargyline, a
      specific monoamine oxidase inhibitor, nor semicarbazide, a specific diamine
      oxidase inhibitor, inhibits the PAO activity of this clone. PAO has been referred
      to as being constitutively expressed. However, 24-h exposure of a non-small cell
      lung carcinoma cell line, NCI H157, to 10 microM of N1,N"-bis(ethyl)norspermine
      results in approximately 5-fold induction of PAO mRNA and a >3-fold induction of
      PAO activity. These results demonstrate that in at least one cell type, PAO is up
      regulated in response to polyamine analogue exposure. The PAO clone described
      here should provide a useful tool, which will facilitate the dissection of the
      role of polyamine catabolism in normal growth and in response to the antitumor
      polyamine analogues.

PMID- 11454678
TI  - Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid
      leukemias with the t(7;12)(q36;p13).
AB  - Recently, we and others reported a recurrent t(7;12)(q36;p13) found in myeloid
      malignancies in children < or =18 months of age and associated with a poor
      prognosis. Fluorescence in situ hybridization studies mapped the 12p13 breakpoint
      to the first intron of ETV6 and narrowed down the region of 7q36 involved. By
      using the sequences made public recently by the Human Genome Project, two
      candidate genes in 7q36 were identified: the homeobox gene HLXB9 and c7orf3, a
      gene with unknown function. Reverse transcription-PCR of two cases with t(7;12),
      using primers for c7orf3 and ETV6, was negative. However, reverse transcription
      PCR for HLXB9-ETV6 demonstrated alternative splicing; the two major bands
      corresponded to fusion of exon 1 of HLXB9 to exons 2 and 3, respectively, of
      ETV6. The reciprocal ETV6-HLXB9 transcript was not detected. It remains to be
      elucidated if the leukemic phenotype is attributable to the formation of the
      HLXB9-ETV6 fusion protein, which includes the helix-loop-helix and E26
      transformation-specific DNA binding domains of ETV6 or to the disruption of the
      normal ETV6 protein.

PMID- 11454679
TI  - Repair of 8-oxodeoxyguanosine lesions in mitochondrial dna depends on the
      oxoguanine dna glycosylase (OGG1) gene and 8-oxoguanine accumulates in the
      mitochondrial dna of OGG1-defective mice.
AB  - Mitochondria are not only the major site for generation of reactive oxygen
      species, but also one of the main targets of oxidative damage. One of the major
      products of DNA oxidation, 8-oxodeoxyguanosine (8-oxodG), accumulates in
      mitochondrial DNA (mtDNA) at levels three times higher than in nuclear DNA. The
      main pathway for the repair of 8-oxodG is the base excision repair pathway
      initiated by oxoguanine DNA glycosylase (OGG1). We previously demonstrated that
      mammalian mitochondria from mice efficiently remove 8-oxodG from their genomes
      and isolated a protein from rat liver mitochondria with 8-oxoguanine (8-oxodG)
      DNA glycosylase/apurinic DNA lyase activity. In the present study, we
      demonstrated that the mitochondrial 8-oxodG DNA glycosylase/apurinic DNA lyase
      activity is the mitochondrial isoform of OGG1. Using mouse liver mitochondria
      isolated from ogg1(-/-) mice, we showed that the OGG1 gene encodes for the
      mitochondrial 8-oxodG glycosylase because these extracts have no incision
      activity toward an oligonucleotide containing a single 8-oxodG DNA base lesion.
      Consistent with an important role for the OGG1 protein in the removal of 8-oxodG
      from the mitochondrial genome, we found that mtDNA isolated from liver from OGG1
      null mutant animals contained 20-fold more 8-oxodG than mtDNA from wild-type
      animals.

PMID- 11454680
TI  - Overexpression of mitochondrial manganese superoxide dismutase protects against
      radiation-induced cell death in the human hepatocellular carcinoma cell line HLE.
AB  - We investigated the potential role of mitochondrial manganese superoxide
      dismutase (Mn-SOD) in protective activity against irradiation by analyzing cell
      viability by a colony formation assay and by detecting apoptosis in stably human
      Mn-SOD gene-transfected HLE, a hepatocellular carcinoma cell line. We found that
      overexpression of Mn-SOD reduced the levels of reactive oxygen species in the
      mitochondria and intracellular phospholipid peroxidation product (4-hydroxy-2
      nonenal) and prevented cell death. The production of intracellular nitric oxide
      after irradiation was not changed by Mn-SOD overexpression. The results suggested
      that Mn-SOD might play an important role in protecting cells against radiation
      induced cell death by controlling the generation of mitochondrial reactive oxygen
      species and intracellular lipid peroxidation.

PMID- 11454681
TI  - Hepatocellular carcinoma results from chronic cyclin D1 overexpression in
      transgenic mice.
AB  - Cyclin D1 is a known oncogene and a key regulator of cell cycle progression.
      Amplification of the cyclin D1 gene and its overexpression have been associated
      with aggressive forms of human hepatocellular carcinoma (HCC). In this study, two
      independent lines of transgenic mice have been generated that express cyclin D1
      under the control of the rat liver fatty acid binding protein promoter. This
      transgene specifically directs expression in the liver and the intestines. RNA
      and protein analysis demonstrated increased expression of the cyclin D1 gene
      product in the liver and bowel when compared with wild-type siblings. Both
      transgenic lines developed progressive liver disease. Examination of H&E stained
      sections of the liver and bowel revealed hyperplastic changes in the liver by 3
      months of age. By 6 months of age, transgenic mice had obvious hepatomegaly and
      histological evidence of dysplasia in the liver. These early changes were
      significantly more dramatic in male animals when compared with female animals. By
      9 months of age adenomas of the liver appeared, progressing to HCC over the
      ensuing 6-month period. By 15-17 months of age, 87% of male and 69% of female
      animals had either adenomatous nodules or HCCs. By 17 months of age, 31% of male
      and female animals had disease that had progressed to HCC. These animals
      represent a unique and significant new model for the study of human HCC. This
      study demonstrates that overexpression of cyclin D1 is sufficient to initiate
      hepatocellular carcinogenesis.

PMID- 11454682
TI  - Extremely low-dose ionizing radiation causes activation of mitogen-activated
      protein kinase pathway and enhances proliferation of normal human diploid cells.
AB  - We demonstrated here that X-ray irradiation at very low doses of between 2 and 5
      cGy stimulated proliferation of normal human diploid cells and human tumor cells.
      Higher doses of irradiation at >1 Gy accumulated p53 protein and induced
      phosphorylation of extracellular signal-regulated kinase (ERK) 1/2.
      Phosphorylation of ERK1/2 decreased with dose down to 50 cGy, however, doses of
      between 5 cGy and 2 cGy phosphorylated ERK1/2 as efficiently as higher doses of X
      rays, whereas the p53 protein level was not changed by doses <50 cGy. We found
      that mitogen-activated protein /ERK kinase (MEK) 1 was phosphorylated with both 2
      cGy and 6 Gy of X-rays, and that activated ERK1/2 augmented phosphorylation of
      Elk-1 protein. The specific epidermal growth factor receptor tyrosine kinase
      inhibitor, AG1478, decreased phosphorylation of the ERK1/2 proteins induced by 2
      cGy or 6 Gy of X-rays, and similar suppressive effect was observed with MEK
      inhibitor, PD98059. Suppression of ERK1/2 phosphorylation with these inhibitors
      alleviated enhanced proliferation of normal human cells by low-dose irradiation.
      Furthermore, overexpression of ERK2 in NCI-H1299 human lung carcinoma cells
      potentiated enhanced proliferation, whereas down-regulation of ERK2 using the
      antisense ERK2 gene abrogated the stimulative effect of low-dose irradiation.
      These results indicate that a limited range of low-dose ionizing radiation
      differentially activates ERK1/2 kinases via activation of epidermal growth factor
      receptor and MEK, which causes enhanced proliferation of cells receiving very low
      doses of ionizing radiation.

PMID- 11454683
TI  - Functional quantification of DNA-binding proteins p53 and estrogen receptor in
      cells and tumor tissues by DNA affinity immunoblotting.
AB  - Functional assays of proteins can monitor the consequences of defects
      attributable to posttranslational activating or inhibitory events as well as to
      genetic mutations. Such assays promise to permit evaluation of cooperating
      oncogenic or tumor suppressor pathways in cells and tumors. As a step toward
      realizing this promise, we designed the DNA affinity immunoblotting (DAI) method
      to measure the activities of multiple sequence-specific DNA-binding proteins
      simultaneously [initially p53 and estrogen receptor (ER)] in lysates of cells or
      frozen tumor tissues. DAI is a novel application of biotin/streptavidin affinity
      chromatography and immunoblotting. The p53 and ER proteins in cell or tissue
      lysates were bound to biotinylated, specific DNA probes, retrieved using a
      streptavidin-conjugated matrix, and then quantified in parallel with total
      protein by immunoblotting. The assay results were reproducible and specifically
      correlated with the known functional status of p53 in mouse and human cells of
      known p53 genotype, including those with low levels of p53 protein. ER
      immunohistochemistry of human breast samples, which is highly correlated with
      functional status and prognosis in human breast cancer, was also highly
      correlated with DNA binding activity results by DAI. In contrast, the p53 protein
      in cells is frequently expressed but inactive, potentially accounting for the
      lack of strict correlation of p53 immunohistochemical or mutational status with
      tumor response to chemotherapy. DAI offers a new means of molecular profiling and
      monitoring of p53 and other DNA-binding protein activities in cells and tumors.
      DAI has applications in the detection and identification of covalently modified
      forms of DNA-binding proteins and in the identification of their interacting
      proteins in complex with DNA.

PMID- 11454684
TI  - High tumor levels of vascular endothelial growth factor predict poor response to
      systemic therapy in advanced breast cancer.
AB  - Vascular endothelial growth factor (VEGF), a potent angiogenic factor, has been
      reported to be associated with a poor prognosis in primary breast cancer and in
      several other cancer types. In the present study, we have measured with ELISA the
      levels of VEGF in cytosolic extracts of 845 primary breast tumors of patients who
      developed a recurrence during follow-up. All of the patients received tamoxifen
      (n = 618) or cyclophosphamide, methotrexate, 5-fluorouracil (CMF) or 5
      fluorouracil, Adriamycin, cyclophosphamide (FAC) chemotherapy (n = 227) as first
      line systemic therapy after diagnosis of advanced disease. VEGF levels were not
      related to age or menopausal status but were negatively related to the cytosolic
      levels of estrogen receptor and progesterone receptor (P < 0.0001). In patients
      who relapsed within 1 year after primary surgery, tumor VEGF levels were higher
      than in patients who showed a longer disease-free interval (P = 0.0005). In
      patients with a first relapse in the viscera, VEGF levels were higher compared
      with those that relapsed to the bone or soft tissue (P = 0.0004). In univariate
      analysis for response to first-line tamoxifen therapy, patients with high or
      intermediate levels showed a poor rate of response, compared with patients with
      low tumor-VEGF levels (P = 0.0001). Similarly, in multivariate analysis for
      response to tamoxifen treatment, corrected for age, site of relapse, disease-free
      interval, and estrogen receptor and progesterone receptor status, VEGF status was
      an independent predictive factor (P = 0.009). In concordance, higher levels of
      VEGF were associated with a short progression-free survival and postrelapse
      overall survival (both, P < 0.0001). On first-line chemotherapy, the rate of
      response decreased with higher tumor levels of VEGF, both in univariate (P =
      0.003) and in multivariate analysis (P = 0.004). Furthermore, higher VEGF levels
      were associated with a short progression-free survival (P = 0.003) and
      postrelapse overall survival (P = 0.001). In conclusion, the tumor VEGF level is
      an important independent marker that predicts a poor efficacy of both tamoxifen
      and chemotherapy in advanced breast cancer. Knowledge of the tumor level of VEGF
      might be helpful in selecting individual patients who may benefit from treatments
      with antiangiogenic agents combined with conventionally used drugs.

PMID- 11454685
TI  - Red meat, family history, and increased risk of gastric cancer with
      microsatellite instability.
AB  - Microsatellite instability (MSI) occurs frequently in sporadic gastric cancer
      (GC) and may define a distinctive molecular pathway of carcinogenesis. We
      evaluated the role of dietary risk factors in GC according to MSI status. A large
      series of 382 GC cases and 561 controls were originally identified in a
      population-based case-control study carried out in the high-risk area around
      Florence, Italy; 126 GC patients were typed for MSI status. A MSI+ phenotype was
      detected in 43 of 126 cases (34.1%), whereas 83 cases were classified as MSI-. A
      multinomial logistic regression model was used to compare the two subgroups of GC
      classified according to MSI status in the same analysis, with all of the
      available population controls. A case-case approach was also used. The risk of
      MSI+ tumors was positively associated with high consumption of red meat and meat
      sauce and negatively associated with consumption of white meat. A positive
      association was also seen with total protein and nitrite intake, whereas no
      relation was found with micronutrient intake. Risk was especially high among
      subjects reporting both a positive GC family history and a high consumption of
      red meat (odds ratio, 25.7; 95% confidence interval, 6.4-102.8). For MSI- tumors,
      a significant protective effect was associated with frequent consumption of
      citrus and other fresh fruit, garlic, legumes, vegetables, and olive oil and with
      high intake of beta-carotene and other antioxidants and sugar, whereas positive
      associations were seen with protein and sodium intake. In summary, a specific
      dietary pattern emerged for MSI+ gastric tumors, suggesting that factors related
      to red meat consumption are involved in this pathway, particularly among
      individuals with a positive family history. In contrast, the risk of MSI- tumors
      was strongly reduced by the frequent consumption of fresh fruit and vegetables.

PMID- 11454686
TI  - Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype
      and reproductive history.
AB  - Women who have inherited a germ-line mutation in the BRCA1 or BRCA2 (BRCA1/2)
      genes have a greatly increased risk of developing breast cancer compared with the
      general population. However, there is also substantial interindividual
      variability in the occurrence of breast cancer among BRCA1/2 mutation carriers.
      We hypothesize that genes involved in endocrine signaling may modify the BRCA1/2
      associated age-specific breast cancer penetrance. We studied the effect of
      alleles at the AIB1 gene using a matched case-control sample of 448 women with
      germ-line BRCA1/2 mutations. We found that these women were at significantly
      higher breast cancer risk if they carried alleles with at least 28 or 29
      polyglutamine repeats at AIB1, compared with women who carried alleles with fewer
      polyglutamine repeats [odds ratio (OR), 1.59; 95% confidence interval (CI), 1.03
      2.47 and OR, 2.85; 95% CI, 1.64-4.96, respectively]. Late age at first live birth
      and nulliparity have been associated with increased breast cancer risk. We
      observed increases in BRCA1/2-associated breast cancer risk in women who were
      either nulliparous or had their first live birth after age 30 (OR, 3.06; 95% CI,
      1.52-6.16). Women were at significantly increased risk if they were nulliparous
      or had a late age at first live birth and had AIB1 alleles no shorter than 28 or
      29 or more AIB1 polyglutamine repeats (OR, 4.62; 95% CI, 2.02-10.56 and OR, 6.97;
      95% CI, 1.71-28.43, respectively) than women with none of these risk factors. Our
      results support the hypothesis that pathways involving endocrine signaling, as
      measured through AIB1 genotype and reproductive history, may have a substantial
      effect on BRCA1/2-associated breast cancer risk.

PMID- 11454687
TI  - Inhibition of DNA replication by tirapazamine.
AB  - Tirapazamine (TPZ) is a hypoxia-selective cytotoxin that is currently being
      examined in Phase II and III clinical trials in combination with radiotherapy and
      cisplatin-based chemotherapy. Reductases convert TPZ to a cytotoxic radical that
      produces DNA damage under hypoxic conditions. Because one or more of the enzymes
      responsible for the bioactivation of TPZ is/are thought to be at or near the
      nuclear matrix, we hypothesized that TPZ may have a major affect on DNA
      replication, a process that is known to occur predominantly at the nuclear
      matrix. To assess the effect of TPZ on DNA replication, we measured the
      incorporation of radioactive thymidine into DNA of HCT116 human colon cancer
      cells and HeLa cells. We show that incorporation of radioactive thymidine is
      dramatically inhibited in cells that are pretreated with TPZ under hypoxic
      conditions. TPZ-induced inhibition of DNA synthesis was much greater than that
      produced by more toxic doses of ionizing radiation. We used the SV40-based in
      vitro DNA replication assay to study the mechanism of inhibition of DNA synthesis
      in cells treated with TPZ. Using this assay, we show that extracts prepared from
      cells treated with TPZ under hypoxic conditions had only 25-50% of the DNA
      replication activity measured in control cells. This reduction in DNA replication
      activity was associated with a reduction in levels of replication protein A (RPA)
      in cytoplasmic extracts used for the in vitro DNA replication assay and could be
      overcome by addition of recombinant human RPA. Furthermore, we show by indirect
      immunofluorescence that TPZ leads to a localization of the p34 subunit of RPA
      (RPA2) to small subnuclear foci. These results show that TPZ dramatically
      inhibits DNA replication and that the mechanism of inhibition, at least in part,
      involves changes in RPA that alter its cellular localization.

PMID- 11454688
TI  - Tumor growth inhibition by arsenic trioxide (As2O3) in the orthotopic metastasis
      model of androgen-independent prostate cancer.
AB  - Arsenic trioxide (As2O3) induces clinical remission of patients with acute
      promyelocytic leukemia. As a novel anticancer agent for treatment of solid
      cancers, As2O3 is promising, but no in vivo experimental investigations of its
      efficacy on solid cancers have been done at clinically obtained concentrations.
      In addition, the cell death mechanism of As2O3 has yet to be clarified,
      especially in solid cancers. In this study, human androgen-independent prostate
      cancer cell lines, PC-3, DU-145, and TSU-PR1 were examined as cellular models for
      As2O3 treatment, and As2O3-induced cell death and inhibition of cell growth and
      colony formation were evaluated. The involvement of p38, c-Jun NH2-terminal
      kinase (JNK), caspase-3, and reactive oxygen species (ROS) were investigated in
      As2O3-induced cell death. Finally, As2O3 was administered to severe combined
      immunodeficient mice inoculated orthotopically with PC-3 cells to estimate in
      vivo efficacy. In all three of the cell lines, at high concentrations, As2O3
      induced apoptosis and, at low concentrations, growth inhibition. As2O3 activated
      p38, JNK, and caspase-3 dose dependently. Treatment with the p38 inhibitor and
      over-expression of dominant-negative JNK did not guard against As2O3-induced cell
      death. In contrast with partial protection by the caspase-3 inhibitor, the
      antioxidant N-acetyl-L-cysteine gave marked protection from As2O3-induced
      apoptosis and eliminated the activation of p38, JNK, and caspase-3, and the
      generation of ROS. The orthotopic murine metastasis model showed in vivo tumor
      growth inhibition in orthotopic and metastatic lesions with no signs of toxicity.
      This study establishes that As2O3 provides a novel, safe approach for treatment
      of androgen-independent prostate cancer. Generation of ROS as a therapeutic
      target for the potentiation of As2O3-induced apoptosis also was shown.

PMID- 11454689
TI  - Effects of angiostatin gene transfer on functional properties and in vivo growth
      of Kaposi's sarcoma cells.
AB  - Gene transfer delivery of endogenous angiogenesis inhibitors such as angiostatin
      would circumvent problems associated with long-term administration of proteins.
      Kaposi's sarcoma (KS), a highly vascular neoplasm, is an excellent model for
      studying tumor angiogenesis and antiangiogenic agent efficacy. We investigated
      the effects of angiostatin gene transfer in in vitro and in vivo models of KS
      induced neovascularization and tumor growth. A eukaryotic expression plasmid and
      a Moloney leukemia virus-based retroviral vector for expression of murine
      angiostatin were generated harboring the angiostatin cDNA with cleavable leader
      signals under the control of either the strong cytomegalovirus promoter/enhancer
      or the Moloney leukemia virus long terminal repeat. Angiostatin secretion was
      confirmed by radioimmunoprecipitation and Western blot analysis. Supernatants of
      angiostatin-transfected cells inhibited endothelial cell migration in vitro.
      Stable gene transfer of the angiostatin cDNA by retroviral vectors in KS-IMM
      cells resulted in sustained angiostatin expression and delayed tumor growth in
      nude mice, which was associated with reduced vascularization. These findings
      suggest that gene therapy with angiostatin might be useful for treatment of KS
      and possibly other highly angiogenic tumors.

PMID- 11454690
TI  - Multimodality therapy with a replication-conditional herpes simplex virus 1
      mutant that expresses yeast cytosine deaminase for intratumoral conversion of 5
      fluorocytosine to 5-fluorouracil.
AB  - Infection of tumor cells by herpes simplex virus 1 (HSV-1) results in cell
      destruction and production of progeny virion in a process referred to as viral
      oncolysis. In this study, an HSV-1 mutant (HSV1yCD) was engineered such that the
      viral ribonucleotide reductase gene is disrupted by sequences encoding yeast
      cytosine deaminase, which efficiently metabolizes the prodrug 5-fluorocytosine (5
      FC) to 5-fluorouracil (5-FU). HSV1yCD-infected cells convert 5-FC to 5-FU, which
      enhances cytotoxicity without significantly reducing viral replication and
      oncolysis. Oncolysis by a replicating HSV-1 mutant combined with therapeutic
      transgene delivery represents a new paradigm; HSV1yCD-infected cells are
      destroyed by viral replication, and uninfected cells are subjected to bystander
      killing from both progeny virion and extracellular diffusion of 5-FU. In
      contrast, HSV1yCD-mediated bioactivation of another prodrug, ganciclovir, impairs
      viral replication. HSV1yCD administered into the portal venous system replicates
      preferentially in liver metastases rather than normal liver. The anti-neoplastic
      activity of HSV1yCD combined with systemic 5-FC administration is greater than
      that achieved with HSV-1 replication alone. Combination oncolysis and prodrug
      bioactivation leads to significant prolongation of survival in mice with diffuse
      liver metastases.

PMID- 11454691
TI  - CV706, a prostate cancer-specific adenovirus variant, in combination with
      radiotherapy produces synergistic antitumor efficacy without increasing toxicity.
AB  - Radiation is an effective means of treating localized prostate cancer. However,
      up to 40% of men with certain risk factors will develop biochemical failure 5
      years after radiotherapy. CV706, a prostate cell-specific adenovirus variant, is
      currently in clinical trials for the treatment of recurrent organ-confined
      prostate cancer. We demonstrated previously that a single administration of CV706
      at 5 x 10(8) particles/mm3 of tumor eliminated established tumors within 6 weeks
      in nude mouse xenografts (Rodriguez et al., Cancer Res. 57: 2559-2563, 1997). We
      now demonstrate that CV706-mediated cytotoxicity is synergistic with radiation.
      In vitro, addition of radiation to CV706 resulted in a synergistic increase of
      cytotoxicity toward the human prostate cancer cell line LNCaP and a significant
      increase of virus burst size, with no reduction in specificity of CV706-based
      cytopathogenicity for prostate cancer cells. In vivo, prostate-specific antigen
      (+) LNCaP xenografts of human prostate cancer were treated with CV706 (1 x 10(7)
      particles/mm3 of tumor), 10 Gy of single fraction local tumor radiation, or both.
      Tumor volumes of the group treated with CV706 or radiation was 97% or 120% of
      baseline 6 weeks after treatment. However, when the same dose of CV706 was
      followed 24 h later with the same dose of radiation, the tumor volume dropped to
      4% of baseline at this time point and produced antitumor activity that was 6.7
      fold greater than a predicted additive effect of CV706 and radiation.
      Histological analyses of tumors revealed that, compared with CV706 or radiation
      alone, combination treatment with two agents increased necrosis by 180% and 690%,
      apoptosis by 330% and 880%, and decreased blood vessel number by 1290% and 600%,
      respectively. Importantly, no increase in toxicity was observed after combined
      treatment when compared with CV706 or radiation alone. These data demonstrate
      that CV706 enhances the in vivo radioresponse of prostate tumors and support the
      clinical development of CV706 as a neoadjuvant agent with radiation for localized
      prostate cancer.

PMID- 11454692
TI  - Resistance to mitoxantrone in multidrug-resistant MCF7 breast cancer cells:
      evaluation of mitoxantrone transport and the role of multidrug resistance protein
      family proteins.
AB  - We examined the role of multidrug resistance protein (MRP) 1 (ABCC1) in the
      emergence of mitoxantrone (MX) cross-resistance in a MCF7 breast cancer cell line
      selected for resistance to etoposide. The resistant cell line, MCF7/VP, expresses
      high levels of MRP1, whereas the parental cell line, MCF7/WT, does not. MCF7/VP
      cells are 6-10-fold cross-resistant to MX when compared with MCF7/WT cells. Drug
      transport studies in intact MCF7/VP cells revealed that MX resistance is
      associated with reduced MX accumulation due to enhanced MX efflux. MX efflux is
      ATP dependent and inhibited by sulfinpyrazone and cyclosporin A. Inhibition of MX
      efflux with these agents sensitizes cells to MX cytotoxicity and partially
      reverses MX resistance in MCF7/VP cells. Whereas resistance is partially
      attributable to increased MX efflux in MRP1-expressing MCF7/VP cells, we found no
      evidence for glutathione or other conjugates of MX in these cells. Moreover,
      glutathione depletion with buthionine sulfoximine had no effect on MX transport
      or sensitivity in MCF7/VP cells. MRP1 substrates are generally amphiphilic anions
      such as glutathione conjugates or require the presence of physiological levels of
      glutathione for MRP1-mediated transport. Therefore we conclude that MRP1
      overexpression is unlikely to be responsible for increased MX efflux and
      resistance in MCF7/VP cells. In considering the potential involvement of other
      MRP family isoforms, a 3-fold increase in the expression of MRP5 was observed in
      MCF7/VP cells. However, stable expression of a transduced MRP5 expression vector
      in MCF7/WT cells failed to confer MX resistance. Because other transporters known
      to be associated with MX resistance, including P-glycoprotein and BCRP/MXR
      (ABCG2), are not expressed in MCF7/VP cells, we conclude that increased MX efflux
      and resistance in MCF7/VP cells is attributable to a novel transport mechanism or
      that MX represents a novel class of cationic, glutathione-independent MRP1
      substrates.

PMID- 11454693
TI  - Inhibition of promyelocytic leukemia (PML)/retinoic acid receptor-alpha and PML
      expression in acute promyelocytic leukemia cells by anti-PML peptide nucleic
      acid.
AB  - The fusion protein promyelocytic leukemia (PML)/retinoic acid receptor (RAR)alpha
      is tightly linked to the pathogenesis of acute promyelocytic leukemia (APL);
      hence, it represents a tumor-associated, transformation-related molecule. In this
      study, three anti-PML adamantyl-conjugated peptide nucleic acid (PNA) oligomers
      previously described as in vitro inhibitors of PML/RARalpha translation were
      combined and used to block PML/RARalpha synthesis in NB4 cells. Cationic
      liposomes were used to achieve sufficient delivery of PNAs into the cells. Upon
      treatment of cells with the liposome/PNA mixture, enhanced cellular uptake of PNA
      (approximately 5-fold compared with control) was obtained. Concomitantly, a
      substantial reduction (>90%) of the expression of PML/RARalpha was observed when
      all of the three PNAs were used together. This resulted in a dramatic effect on
      the number and viability of NB4 cells in culture after 48 h of treatment. This
      phenomenon was preceded by induction of apoptosis that could be observed 24 h
      after treatment. No sign of granulocytic differentiation was observed after
      treatment. These effects were also noted on other leukemic cell lines that
      express PML but not the fusion transcript. These results show that it is possible
      to deliver PNA into hematopoietic cells and obtain specific gene inhibition, and
      they suggest that a growth inhibitory effect on acute promyelocytic leukemia
      cells can be obtained through the block of PML/RARalpha and PML expression.

PMID- 11454694
TI  - 8-chloro-cAMP and 8-chloro-adenosine act by the same mechanism in multiple
      myeloma cells.
AB  - Previous work with 8-chloro-cAMP (8-Cl-cAMP) has raised questions as to whether
      it works as a cAMP analogue or as a nucleoside analogue after its conversion to 8
      chloro-adenosine (8-Cl-Ado). Although degradation of 8-Cl-cAMP to 8-Cl-Ado in
      culture medium or plasma has been shown, cellular pharmacology data are missing.
      The purpose of the present study was to identify the cellular metabolism of these
      drugs and their actions in a human multiple myeloma cell line. The cells were
      incubated with either 8-Cl-Ado or 8-Cl-cAMP to follow the cellular metabolism of
      these agents. Both 8-Cl-cAMP and 8-Cl-Ado incubation resulted in the accumulation
      of 8-Cl-Ado mono-, di-, and tri-phosphate (8-Cl-ATP), however, the triphosphate
      was the major cytotoxic metabolite. Accumulation of 8-Cl-ATP was dependent on
      both the exogenous concentration of 8-Cl-Ado and incubation time. At the 10
      microM level of 8-Cl-Ado, >400 microM 8-Cl-ATP accumulated in multiple myeloma
      cells after continuous incubation for 12 h. Similar incubation with 8-Cl-cAMP
      also resulted in accumulation of 8-Cl-ATP in the cells, albeit at a lower level.
      The formation of 8-Cl-ATP from 8-Cl-cAMP was inhibited by >80% in the presence of
      the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine in the medium,
      suggesting extracellular conversion of 8-Cl-cAMP to 8-Cl-Ado. Cells lacking Ado
      kinase did not accumulate 8-Cl-ATP, either from 8-Cl-Ado or 8-Cl-cAMP, and were
      resistant to these agents. There was also a decline in the endogenous level of
      the cellular ATP pool parallel to the accumulation of 8-C1-ATP. The elimination
      of 8-Cl-ATP was biphasic and slow from the cells. The accumulation of 8-Cl-ATP
      and a decline in the ATP pool inhibited RNA synthesis but did not affect DNA
      synthesis for up to 12 h of incubation. Taken together, these data demonstrate
      that the cytotoxic metabolite of 8-Cl-Ado and 8-Cl-cAMP is 8-Cl-ATP. Hence, 8-Cl
      cAMP serves as a prodrug and is converted to 8-Cl-Ado in medium with subsequent
      phosphorylation to accumulate as 8-Cl-ATP in cells. At the cellular level, 8-Cl
      ATP is associated with a decrease in the endogenous ATP pool; at the nuclear
      level, it inhibits RNA synthesis.

PMID- 11454695
TI  - A-204197, a new tubulin-binding agent with antimitotic activity in tumor cell
      lines resistant to known microtubule inhibitors.
AB  - Drug resistance is a prevalent problem in the treatment of neoplastic disease,
      and the effectiveness of many clinically useful drugs is limited by the fact that
      they are substrates for the efflux pump, P-glycoprotein. Because there is a need
      for new compounds that are effective in treating drug-resistant tumors, we tested
      A-204197 (4-[4-acetyl-4,5-dihydro-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2
      yl]-N,N-dimethylbenzeneamine), a novel oxadiazoline derivative with
      antiproliferative properties, on cell lines that were either sensitive or
      resistant to known microtubule inhibitors. Cell lines that were resistant to
      paclitaxel, vinblastine, or colchicine were equally sensitive to A-204197
      (proliferation IC50s ranging from 36 to 48 nM) despite their expression levels of
      P-glycoprotein. The effect of A-204197 on cell growth was associated with cell
      cycle arrest in G2-M, increased phosphorylation of select G2-M checkpoint
      proteins, and apoptosis. In competition-binding assays, A-204197 competed with
      [3H]-labeled colchicine for binding to tubulin (K(i) = 0.75 microM); however, it
      did not compete with [3H]-labeled paclitaxel. A-204197 prevented tubulin
      polymerization in a dose-dependent manner (IC50 = 4.5 microM) in vitro and
      depolymerized microtubules in a time-dependent manner in cultured cells. These
      findings indicate A-204197 is a promising new tubulin-binding compound with
      antimitotic activity that has potential for treating neoplastic diseases with
      greater efficacy than currently used antimitotic agents.

PMID- 11454696
TI  - Triterpenoid saponins from Acacia victoriae (Bentham) decrease tumor cell
      proliferation and induce apoptosis.
AB  - This report describes the isolation and partial purification of novel
      triterpenoid saponins [Fraction 35 (F035)] and two pure biologically active
      derivatives (termed avicins D and G) from Acacia victoriae, an Australian desert
      tree of the Leguminosae family. F035 and the avicins markedly inhibited the
      growth of several tumor cell lines with minimum growth inhibition in human
      foreskin fibroblasts, mouse fibroblasts, and immortalized breast epithelial cells
      at similar concentrations. F035 and the avicins induced cell cycle (G1) arrest of
      the human MDA-MB-453 breast cancer cell line and apoptosis of the Jurkat (T-cell
      leukemia) and the MDA-MB-435 breast cancer cell line. The triterpenoid saponins
      also partially inhibited phosphatidylinositol 3-kinase activity in Jurkat T cells
      in a time-dependent manner and phosphorylation in the downstream protein Akt,
      whereas no affect was seen on the Ras/mitogen-activated protein kinase cascade.
      These observations as well as other work from our laboratory demonstrating
      mitochondrial perturbation, chemoprevention, and inhibition of nuclear factor
      kappaB suggest that triterpenoid saponins from A. victoriae have potential as
      novel anticancer agents. Recent work linking Akt signaling with glucose
      metabolism, stress resistance, and longevity suggests other potential
      applications of these compounds.

PMID- 11454697
TI  - Pharmacodynamic-mediated reduction of temozolomide tumor concentrations by the
      angiogenesis inhibitor TNP-470.
AB  - The angiogenic phenotype is associated with increased tumor neovascularization
      and a state of vascular hyperpermeability to macromolecules. Angiogenesis
      inhibitors could reverse these processes, resulting in tumor capillaries that
      have normal membrane permeability. It was proposed that the switch from a
      hyperpermeable to a normal permeable state could have the untoward effect of
      decreasing tumor concentrations of anticancer drugs coadministered with
      angiogenesis inhibitors. The current investigation evaluated a potential drug
      interaction between the angiogenesis inhibitor O-(N-chloroacetyl-carbamoyl)
      fumagillol (TNP-470) and the alkylating agent temozolomide (TMZ), in xenograft
      models that differentially expressed vascular endothelial growth factor (VEGF), a
      driving force for angiogenesis. Nude rats bearing either s.c. low VEGF (V-) or
      high VEGF (V+) or intracerebral V+ gliomas were administered either a multiple
      dose regimen of TNP-470 or vehicle control. One day after the last dose of
      vehicle or TNP-470, a steady-state dosing regimen of TMZ was administered with
      subsequent collection and high-performance liquid chromatography analysis of
      plasma and either tumor homogenate or tumor microdialysis steady-state TMZ
      concentrations, and in some cases [5-(3-methyltriazen-1-yl)imidazole-4
      carboximide] MTIC, its active metabolite. Microvessel density (MVD) was
      quantitated by image analysis using an anti-CD31 method. Statistical analyses of
      pharmacokinetic and pharmacodynamic end points in the control and TNP-470
      treatment groups were completed by nonparametric tests. In both the s.c. and
      intracerebral V+ models, TNP-470 treatment produced significant reductions in TMZ
      tumor concentrations and tumor:plasma concentration ratios compared with control,
      being reduced an average of 25% and 50% in the s.c. and intracerebral tumors,
      respectively. MTIC concentrations in V+ s.c. tumors also were reduced by 50% in
      the presence of TNP-470. Consistent with the lower extent of neovascularization
      in the V- tumors, TMZ and MTIC tumor concentrations were not different in TNP-470
      and control treatment groups in s.c. tumors. MVD was reduced by TNP-470 compared
      with vehicle control in the V+ tumors, but was unaltered in V- tumors, attesting
      to the use of MVD as a pharmacodynamic end point and the effectiveness of TNP-470
      as an angiogenesis inhibitor. Angiogenesis inhibitor's pharmacodynamic actions on
      tumor angiogenesis can produce a reduction in tumor concentrations of
      coadministered anticancer agents. It is increasingly important to understand the
      pharmacokinetic and pharmacodynamic behavior of each class of drug so that
      optimal dosing regimens can be designed.

PMID- 11454698
TI  - Tetra-O-methyl nordihydroguaiaretic acid induces G2 arrest in mammalian cells and
      exhibits tumoricidal activity in vivo.
AB  - The transcription inhibitor tetra-O-methyl nordihydroguaiaretic acid (M4N) was
      found to arrest the proliferation of C3, C33a, CEM-T4, and TC-1 cells in culture
      at the G2 stage of the cell cycle. Investigation into the mechanism of arrest
      revealed that M4N reduces mRNA levels and subsequent protein production of the
      cyclin-dependent kinase CDC2, resulting in the inactivation of the CDC2/cyclin B
      complex (maturation promoting factor). When injected intratumorally in a C3-cell
      induced C57bl/6 mouse tumor model system, M4N demonstrated substantial
      tumoricidal activity that correlated with a reduction in tumor cell CDC2 protein
      levels. These findings suggest that M4N may be a useful chemotherapeutic agent
      for the control of unregulated cellular proliferation.

PMID- 11454699
TI  - Pharmacogenomic dissection of resistance to thymidylate synthase inhibitors.
AB  - Chemoresistance is a major obstacle for successful cancer treatment. Gene
      amplification and altered expression are the main genetic mechanisms of tumor
      chemoresistance. Previously, only a limited number of genes were analyzed in each
      individual study using traditional molecular methods such as Northern and
      Southern blotting. In this study, the global gene expression patterns of 1176
      genes in a panel of five thymidylate synthase (TS) inhibitor [raltitrexed (TDX)
      and 5-fluorouracil (5-FU)] resistant and sensitive parent cell lines were
      investigated using cDNA array technology. Only 28 of 1176 genes were altered >1.5
      fold among resistant cells, with 2 genes (TS and YES1) consistently higher in the
      panel. TS mRNA and protein were consistently overexpressed in all drug-resistant
      tumor cell lines compared with the sensitive parent cell lines. Southern blot and
      FISH analysis demonstrated that the TS gene was amplified in 5-FU- and TDX
      resistant cell lines. YES1 mRNA and protein were overexpressed in four drug
      resistant tumor cell lines but were not overexpressed in the lymphoblast cell
      line W1L2(TDX), although the YES1 gene was highly amplified in these cells. The
      fact that W1L2 has high level (>10-fold) resistance to TS inhibitor in the
      absence of high YES1 expression leads to a conclusion that YES1 has no direct
      role in this drug resistance process. By narrowing the search from 1176 to 2
      genes, the analysis of in vitro TDX and 5-FU resistance becomes more
      straightforward for confirmatory studies. These data provide encouragement that
      comprehensive transcript analysis will aid the quest for more enlightened
      therapeutics.

PMID- 11454700
TI  - Identification of fibroblast growth factor-5 as an overexpressed antigen in
      multiple human adenocarcinomas.
AB  - Methodology for identifying tumor-associated antigens recognized by T cells has
      been successfully used to clone antigens from melanoma cells. Similar efforts for
      nonmelanoma tumors have had limited success with few antigens identified. To
      identify potentially relevant tumor-associated antigens expressed in renal cell
      carcinoma cell lines, a tumor-specific CTL clone was established from tumor
      infiltrating lymphocytes from a regressing pulmonary lesion. This CTL recognized
      nonmutated fibroblast growth factor-5 (FGF-5). Quantitative real-time reverse
      transcription PCR revealed that FGF-5 was overexpressed in the majority of renal
      cell carcinomas, as well as in some prostate carcinoma and breast carcinoma
      lines. FGF-5 expression by quantitative real-time reverse transcription PCR in
      normal tissues was below the recognition threshold for this CTL. As a normal
      protein with significant overexpression by multiple adenocarcinomas and little
      normal tissue expression, FGF-5 represents an immunotherapy target with potential
      utility against a broad array of nonmelanoma cancers.

PMID- 11454701
TI  - IgEs targeted on tumor cells: therapeutic activity and potential in the design of
      tumor vaccines.
AB  - Surface-bound IgE play a central role in antiparasite immunity; to exploit IgE
      driven immune mechanisms in tumor prevention and control, monoclonal IgEs of
      irrelevant specificity were loaded through biotin-avidin bridging onto tumor
      cells, either by systemic administration to tumor-bearing mice or pre-loading of
      tumor cells before inoculation. Here we show that systemic administration of
      biotinylated IgEs to mice bearing tumors pre-targeted with biotinylated
      antibodies and avidin significantly decreased tumor growth rate. In addition, as
      compared with IgG-loaded control cells, inoculation of suboptimal doses of IgE
      loaded tumor cells suppressed tumor formation in a fraction of animals and
      induced protective host immunity by eliciting tumor-specific T-cell responses.
      Similarly, tumor vaccination experiments showed that irradiated tumor cells (IgE
      loaded by biotin-avidin bridging) conferred protective immunity at doses 100-fold
      lower than the corresponding control cells without IgE. Finally, in vivo
      depletion of eosinophils or T cells abrogated IgE-driven tumor growth inhibition.
      These results demonstrate that IgEs targeted on tumor cells not only possess a
      curative potential but also confer long-term antitumor immunity and that IgE
      driven antitumor activity is not restricted to the activation of innate immunity
      effector mechanisms but also results from eosinophil-dependent priming of a T
      cell-mediated adaptive immune response. This suggests a potential role for IgEs
      in the design of new cell-based tumor vaccines.

PMID- 11454702
TI  - Antimetastatic effect of CpG DNA mediated by type I IFN.
AB  - The mechanisms involved in the antimetastatic effect of CpG-containing DNA were
      investigated in a mouse model of experimental metastasis. Tumor cell colony
      formation in lungs or livers of mice after i.v. inoculation with syngeneic
      fibrosarcoma or thymoma cells was determined. The i.v. injection of plasmid DNA
      or synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs
      before tumor cell application strongly inhibited metastasis. Because synthetic
      CpG-ODN was not directly tumor cytotoxic, the target cells for this CpG-ODN
      effect were determined. The cytotoxic activity on standard natural killer (NK)
      targets as well as on fibrosarcoma cells of splenic NK cells and NKT cell
      containing liver mononuclear cells derived from CpG-ODN-treated mice was strongly
      enhanced. Participation of NK/NKT cells in the CpG-induced antimetastatic effect
      was demonstrated by reduction of the antimetastatic effect in mice depleted of
      NK/NKT cells and beta2-microglobulin-deficient mice. Neutralization of
      interleukin 12, interleukin 18, or IFN-gamma did not interfere with the CpG
      induced antimetastatic effect. However, in sera of CpG-ODN-treated mice, high
      levels of IFN-alpha were detected, and in IFN-alpha/beta receptor-deficient mice,
      the CpG-ODN-induced antimetastatic effect was strongly reduced. These data
      indicate that CpG-ODNs activate NK/NKT cells for antimetastatic activity
      indirectly via IFN-alpha/beta receptor activation. The exploitation of the
      stimulatory activity of CpG-ODN for the innate immune system might be a useful
      strategy for antimetastatic therapy.

PMID- 11454703
TI  - Human telomerase reverse transcriptase promoter regulation in normal and
      malignant human ovarian epithelial cells.
AB  - The telomerase RNA-protein complex responsible for maintenance of telomeric DNA
      at chromosome ends, is usually inactive in most primary somatic human cells, but
      is specifically activated with in vitro immortalization and during tumorigenesis.
      Although expression of the RNA component of telomerase appears to be
      constitutive, the expression pattern of human telomerase reverse transcriptase
      (hTERT), the catalytic subunit of telomerase, is correlated with measured enzyme
      activity. In particular, a >80% concordance has been reported between telomerase
      activity and hTERT mRNA expression in ovarian tumors. Accordingly, to learn more
      about the mechanism regulating hTERT gene expression in ovarian carcinoma, we
      have performed a detailed analysis of the 5'-flanking promoter region of the
      hTERT gene. We have reported previously the isolation and analysis of a 5.8-kb
      genomic fragment containing the human hTERT gene promoter (M. Tzukerman et al.,
      Mol. Biol. Cell, 11: 4381-4391, 2000). Deletion analysis of this promoter was
      carried out using transient transfection of promoter-reporter constructs in four
      different telomerase-expressing, ovarian carcinoma-derived cell lines, the
      tumorigenic properties of which have been characterized, and was compared with
      telomerase-negative primary human fibroblasts and nontransformed ovarian
      epithelial cells. These assays have shown that the hTERT promoter is inactive in
      telomerase-negative cells and is active in telomerase-positive cell lines. A core
      promoter of 283 bp upstream of the transcription initiation site (TI) was found
      to be sufficient for maximum promoter activity, suggesting the presence of
      inhibitory elements within the larger promoter sequence. Gel shift analysis of
      the core promoter using nuclear extracts from the ovarian and control cell lines
      revealed specific transcription factor binding using extracts from telomerase
      positive cells. Among the binding elements, we identified two E-boxes (CACGTG) as
      well as a novel element (MT-box), which we identified recently in a number of
      differentiation systems. Site-directed mutagenesis was used to introduce
      mutations into this novel transcription factor binding element. These mutations
      significantly affect the transcriptional activity of hTERT promoter in a cell
      type-specific manner and suggest that the transcription factors that bind to the
      E-box and the novel element cooperatively function as major determinants of hTERT
      expression and telomerase activity in ovarian cancer. Further comparison of
      promoter activity, telomerase activity, and telomere length among the different
      ovarian cancer cells indicated that a threshold level of telomerase activity is
      apparently sufficient to protect telomere integrity and permit the immortal state
      of the different ovarian cancer cell lines.

PMID- 11454704
TI  - Redox modulation of the pro-fibrogenic mediator plasminogen activator inhibitor-1
      following ionizing radiation.
AB  - Fibrosis is a common form of normal tissue damage after exposure to a wide
      variety of insults believed to involve oxidative stress. Plasminogen activator
      inhibitor-1 (PAI-1) is thought to play a major role in the development of
      progressive fibrosis via the inhibition of extracellular matrix degradation.
      Because radiation causes oxidative injury, which has been shown to trigger
      fibrogenic responses, the present study was designed to test the hypothesis that
      PAI-1 expression is redox-regulated after irradiation. Irradiating rat kidney
      tubule epithelial cells (NRK52E) with 1-20 Gy gamma-rays led to dose-dependent
      increases in steady-state levels of PAI-1 mRNA and immunoreactive protein within
      24 and 48 h, respectively. Enhancement of intracellular soluble thiol pools after
      incubation with N-acetylcysteine (2.5 mM), from 3.27 +/- 0.27 nM/mg protein to
      5.34 +/- 0.52 nM/mg protein in cells incubated with N-acetylcysteine 30 min
      before and assessed 4 h after irradiation, abolished the radiation-induced up
      regulation of PAI-1. In addition, overexpression of catalase inhibited radiation
      induced increases in PAI-1 expression, suggesting a mechanistic role for hydrogen
      peroxide (H2O2) in regulating PAI-1 expression after oxidative insult. In support
      of this notion, incubating NRK52E cells with H2O2 (100 microM) also led to a
      nearly 3-fold increase in PAI-1 gene expression. These results demonstrate that
      PAI-1 is redox-regulated after exposure to ionizing radiation or H2O2 and suggest
      that H2O2 scavenging might represent a fundamental mechanism for modulating
      fibrogenic disease via inhibition of the induction of profibrogenic mediators
      after acute or chronic oxidative stress.

PMID- 11454705
TI  - An overview of the MAGE gene family with the identification of all human members
      of the family.
AB  - The first human members of the MAGE gene family that have been described are
      expressed in tumor cells but silent in normal adult tissues except in the male
      germ line. Hence, they encode strictly tumor-specific antigens that represent
      attractive targets for cancer immunotherapy. However, other members of the family
      were recently found to be expressed in normal cells, indicating that the family
      is larger and more disparate than initially expected. We therefore performed a
      database screening to identify all of the recorded members of both classes of
      human MAGE genes. This report provides an overview of the MAGE family and
      proposes a general nomenclature for all of the MAGE genes identified thus far. We
      found that the MAGE-D genes were particularly well conserved between man and
      mouse, suggesting that they exert important functions. In addition, the genomic
      structure of the MAGE-D genes indicates that one of them corresponds to the
      founder member of the family, and that all of the other MAGE genes are retrogenes
      derived from that common ancestral gene. Intriguingly, the COOH-terminal domain
      of MAGE-D3 was found to be identical to trophinin, a previously described protein
      believed to be involved in embryo implantation.

PMID- 11454706
TI  - Heterozygosity for the mouse Apex gene results in phenotypes associated with
      oxidative stress.
AB  - Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base
      excision repair, required for the repair of spontaneous base damage that arises
      as a result of oxidative damage to DNA. In mice, this endonuclease is coded by
      the Apex gene, disruption of which is incompatible with embryonic life. Here we
      confirm the embryonic lethality of Apex-null mice and report the phenotypic
      characterization of mice that are heterozygous mutants for the Apex gene (Apex+/
      ). We show that Apex heterozygous mutant cells and animals are abnormally
      sensitive to increased oxidative stress. Additionally, such animals manifest
      elevated levels of oxidative stress markers in serum, and we show that dietary
      supplementation with antioxidants restores these to normal levels. Apex+/-
      embryos and pups manifest reduced survival that can also be partially rescued by
      dietary supplementation with antioxidants. These results are consistent with a
      proposed role for this enzyme in protection against the deleterious effects of
      oxidative stress and raise the possibility that humans with heterozygous
      mutations in the homologous HAP1 gene may be at increased risk for the phenotypic
      consequences of oxidative stress in cells.

PMID- 11454707
TI  - Hypermethylation leads to silencing of the SYK gene in human breast cancer.
AB  - A number of cancer-associated genes have been shown to be inactivated by
      hypermethylation of CpG islands during breast tumorigenesis. SYK, a candidate
      tumor suppressor, has been found not expressed in a subset of breast cancer cell
      lines, but the mechanism by which SYK is silenced is unclear. In this study, we
      examined the 5' CpG island methylation status of the SYK gene in breast cancer
      cell lines and primary breast cancer tissues. We found SYK 5' CpG
      hypermethylation in 30% (6/20) of breast cancer cell lines, and the aberrant
      methylation status was strongly associated with loss of SYK gene expression.
      Treatment of cells with a methylation inhibitor, 5-aza-2'-deoxycytidine, led to a
      reactivation of SYK expression in SYK-negative cells, as detected by reverse
      transcription-PCR. Using methylation-specific PCR, we demonstrated that SYK is
      hypermethylated in 32% (12/37) of unselected breast tumors, whereas all of the
      matched neighboring normal breast tissues exhibited unmethylated DNA status. We
      concluded that SYK is frequently inactivated through an epigenetic pathway in
      breast cancer. Because SYK has been shown to function as a tumor suppressor, and
      its loss of expression in breast cancer has been correlated with tumor
      invasiveness, the aberrant SYK methylation is responsible for the loss of
      expression and may consequently play a permissive role for tumor aggressiveness.

PMID- 11454708
TI  - Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic
      effects of multiple heparin-binding growth factors in breast cancer cells.
AB  - Glypicans are a family of glycosylphosphatidylinositol-anchored cell surface
      heparan sulfate proteoglycans implicated in the control of cellular growth and
      differentiation. Here we show that glypican-1 is strongly expressed in human
      breast cancers, whereas expression of glypican-1 is low in normal breast tissues.
      In contrast, the expression of glypican-3 and -4 is only slightly increased in
      breast cancers by comparison with normal breast tissues, and glypican-2 and -5
      are below the level of detection by Northern blotting in both normal and cancer
      samples. Treatment of MDA-MB-231 and MDA-MB-468 breast cancer cells with
      phosphoinositide-specific phospholipase-C abrogated the mitogenic response to two
      heparin-binding growth factors, heparin-binding epidermal growth factor-like
      growth factor and fibroblast growth factor 2. Stable transfection of these cells
      with a glypican-1 antisense construct markedly decreased glypican-1 protein
      levels and the mitogenic response to the same heparin-binding growth factors, as
      well as that to heregulin alpha, heregulin beta, and hepatocyte growth factor.
      Syndecan-1 was also expressed at high levels in both breast cancer tissues and
      breast cancer cells when compared with normal breast tissues. There was a good
      correlation between glypican-1 and syndecan-1 expression in the tumors. However,
      clones expressing the glypican-1 antisense construct did not exhibit decreased
      syndecan-1 levels, indicating that loss of responsiveness to heparin-binding
      growth factors in these clones was not due to altered syndecan-1 expression.
      Furthermore, 8 of 10 tumors with stage 2 or 3 disease exhibited high levels of
      glypican-1 by Northern blot analysis. In contrast, low levels of glypican-1 mRNA
      were evident in 1 of 10 tumors with stage 2 or 3 disease and in 9 of 10 tumors
      with stage 1 disease. Taken together, these data suggest that glypican-1 may play
      a pivotal role in the ability of breast cancer cells to exhibit a mitogenic
      response to multiple heparin-binding growth factors and may contribute to disease
      progression in this malignancy.

PMID- 11454709
TI  - Detection of peritoneal micrometastases of gastric carcinoma with green
      fluorescent protein and carcinoembryonic antigen promoter.
AB  - The aim of this study was to specifically visualize micrometastases in the
      peritoneal cavity, which cannot be detected by conventional methods, by using
      enhanced Green Fluorescent Protein (EGFP) containing carcinoembryonic antigen
      (CEA) promoter in an upstream position. In in vitro experiments, two cell lines
      from human gastric cancer, MKN45 and MKN1, and a cell line from human
      fibrosarcoma, HT1080, were transduced with pCEA-EGFP, which contains the CEA
      promoter region. MKN45 and MKN1, which expressed CEA mRNA, showed positive
      fluorescence after transduction of pCEA-EGFP, whereas HT1080 did not. In in vivo
      experiments, 7 days after 10(7) MKN45 had been injected into the peritoneal
      cavity of BALB/c nude mice, pCEA-EGFP was transduced in the peritoneal cavity
      using a fusogenic liposome with the envelope protein of Hemagglutinating Virus of
      Japan on the surface. On the peritoneum of the abdominal wall, fluorescent
      nodules were detected by fluorescence stereomicroscopy. These nodules had a
      minimal size of approximately 0.15 mm and could not be detected by conventional
      stereomicroscopy or macroscopy. They were histologically confirmed to be cancer
      cells by H&E staining. The results suggest that visualization of peritoneal
      micrometastasis of gastric cancer using CEA promoter and EGFP can offer a new
      strategy for diagnosis of micrometastasis.

PMID- 11454710
TI  - A primary tumor promotes dormancy of solitary tumor cells before inhibiting
      angiogenesis.
AB  - Mechanisms that regulate the transition of micrometastases from clinically
      undetectable and dormant to progressively growing are critically important but
      poorly understood in cancer biology. Here we examined the effect of a primary
      tumor on the growth of solitary tumor cells in the mouse liver, as well as on the
      development of tumor angiogenesis in a dorsal skin-fold chamber. s.c. placement
      of a CT-26 (BALB/c-derived mouse colon carcinoma) primary tumor markedly
      inhibited development of liver metastasis in BALB/c mice after subsequent
      intraportal injection of tumor cells. Dorsal skin-fold chamber experiments showed
      that this growth inhibition paralleled a strong antiangiogenic effect by the
      primary tumor. Furthermore, intravital microscopy of the liver after intraportal
      injection of green fluorescent protein-expressing tumor cells showed that primary
      tumors promoted dormancy of single tumor cells for up to 7 days.
      Immunohistological staining for Ki-67 confirmed that these solitary cells were
      indeed dormant. In contrast, in the absence of a primary tumor, GFP-expressing
      tumor cells quickly developed into micrometastases. Thus, primary CT-26 tumor
      implants nearly abrogated tumor metastasis by inhibition of angiogenesis and by
      promoting a state of single-cell dormancy. Knowledge of the mechanism underlying
      this dormancy state could result in the development of new therapeutic tools to
      fight cancer.

PMID- 11454711
TI  - Telomerase inhibition in RenCa, a murine tumor cell line with short telomeres, by
      overexpression of a dominant negative mTERT mutant, reveals fundamental
      differences in telomerase regulation between human and murine cells.
AB  - In contrast to human primary fibroblasts, mouse embryonic fibroblasts have
      telomerase activity, immortalize spontaneously in culture, and can be
      neoplastically transformed by oncogenic insult. Ectopic expression of the human
      telomerase catalytic subunit, human telomerase reverse transcriptase (hTERT), in
      human primary cells allows both spontaneous immortalization and neoplastic
      transformation by oncogenes. This suggests that telomerase activity, as well as
      the fact that mouse telomeres are longer than human telomeres, may explain some
      of the differences in cellular control between human and murine cells. Telomerase
      inhibition in immortal or transformed human cells using dominant negative hTERT
      mutants leads to telomere shortening and cell death. Here we study the effect of
      expression of a dominant negative mutant of the catalytic subunit of mouse
      telomerase, mTERT-DN, in a murine kidney tumor cell line, RenCa, whose telomeres
      are similar in length to human telomeres. After showing initial telomerase
      activity inhibition and telomere shortening, all clones expressing mTERT-DN
      reactivated telomerase and showed normal viability, in contrast with that
      described for human cells. This efficient telomerase reactivation coincided with
      a significant increase in the endogenous TERT mRNA levels in the presence of
      mTERT-DN expression. The results presented here reveal the existence of
      fundamental differences in telomerase regulation between mice and man.

PMID- 11454712
TI  - Plasminogen activator inhibitor-1 promotes angiogenesis by stimulating
      endothelial cell migration toward fibronectin.
AB  - Increased expression of plasminogen activator inhibitor-1 (PAI-1) in cancer
      patients is associated with unfavorable outcome, and the reason for this paradox
      has been poorly understood. We have previously reported elevated levels of PAI-1
      in primary tumors of advanced neuroblastomas (Y. Sugiura et al., Cancer Res., 59:
      1327-1336, 1999). Here we demonstrate that PAI-1 is coexpressed with the
      angiogenesis marker alpha(v)beta3 integrin in blood vessels of primary
      neuroblastoma tumors, suggesting that PAI-1 plays a role in angiogenesis. Using
      human brain microvascular endothelial cells (HBMECs), we found that PAI-1
      inhibits alpha(v)beta3 integrin-mediated cell adhesion to vitronectin but
      promotes alpha5beta1-mediated migration from vitronectin toward fibronectin.
      Inhibition of vitronectin adhesion by PAI-1 did not induce HBMEC apoptosis. PAI-1
      also inhibited endothelial tube formation on Matrigel in the presence of
      vitronectin but had a stimulatory effect in the presence of fibronectin. This
      effect of PAI-1 on microvascular endothelial cells is primarily related to the
      ability of PAI-1 to bind to vitronectin via its NH2-terminal domain and to
      interfere with cell adhesion to vitronectin. We propose that PAI-1 acts as a
      positive switch for angiogenesis by promoting endothelial cell migration away
      from their vitronectin-containing perivascular space toward fibronectin-rich
      tumor tissue. These observations provide a novel explanation for the enhancing
      effect of PAI-1 in cancer progression.

PMID- 11454713
TI  - High glycolytic activity in rat glioma demonstrated in vivo by correlation peak
      1H magnetic resonance imaging.
AB  - High-grade brain tumors are known to have a high rate of glucose (Glc)
      consumption. Postmortem measurements have suggested that Glc content in
      experimental brain tumors is relatively low. We used magnetic resonance
      spectroscopy to investigate this, in vivo, in the brains of seven rats bearing
      intracerebral C6 gliomas. We combined the high spectral resolution allowed by two
      dimensional proton nuclear magnetic resonance with spatial encoding by magnetic
      field gradient pulses to obtain in vivo maps of Glc, alanine, hypotaurine,
      aspartate, phosphoethanolamine, Glu/Gln, N-acetylaspartate (NAA),
      phosphocreatine/creatine (PCr/Cr), choline-containing compounds, and lactate
      (Lac) (some of which are involved in energy metabolism). Compared with normal
      brain tissue, the main differences found in the gliomas were that Glc, NAA,
      PCr/Cr, and aspartate concentrations were much lower, whereas concentrations of
      alanine, hypotaurine, phosphoethanolamine, and Lac were higher, whatever the
      extent of necrosis. A striking observation is the similarity of the NAA and Glc
      images: the concentrations of both metabolites are lower in the tumor than they
      are in the contralateral brain. If Glc was completely absent from the tumor
      tissue, and if the residual Glc level was due only to a partial volume effect
      like that for NAA, a neuronal marker, the ratio [Glc]tumor/[Glc]contralateral
      tissue, should be similar to that found for NAA. The ratio for Glc was 0.48 +/-
      0.22 (+/- SD; n = 6), a ratio similar to that found for PCr/Cr (0.50 +/- 0.19)
      but significantly higher than that obtained for NAA (0.29 +/- 0.07). This
      observation indicates that a measurable Glc concentration is still present in the
      tumor tissue. Intense glycolysis in tumor cells may explain the increased
      production of Lac and alanine and decreased amount of Glc. These nuclear magnetic
      resonance measurements of metabolite concentrations are complementary to positron
      emission tomography, which measures Glc consumption.

PMID- 11454714
TI  - Overexpression of alpha4 chain-containing laminins in human glial tumors
      identified by gene microarray analysis.
AB  - Differential gene expression in tumors often involves growth factors and
      extracellular matrix/basement membrane components. Here, 11,000- gene microarray
      was used to identify gene expression profiles in brain tumors including high
      grade gliomas [glioblastoma multiforme (GBM) and anaplastic astrocytoma], low
      grade astrocytomas, or benign extra-axial brain tumors (meningioma) in comparison
      with normal brain tissue. Histologically normal tissues adjacent to GBMs were
      also studied. All GBMs studied overexpressed 14 known genes compared with normal
      human brain tissue. Overexpressed genes belonged to two broad groups: (a) growth
      factor-related genes; and (b) structural/extracellular matrix-related genes. For
      most of these 14 genes, expression levels were lower in low-grade astrocytoma
      than in GBM and were barely detectable in normal brain. Despite normal-appearing
      histology, gene expression patterns of tissues immediately adjacent to GBM were
      similar to those of their respective primary GBMs. Two genes were consistently up
      regulated in both high-grade and low-grade gliomas, as well as in histologically
      normal tissues adjacent to GBMs. These genes coded for the epidermal growth
      factor receptor (previously reported to be overexpressed in gliomas) and for the
      alpha4 chain of laminin, a major blood vessel basement membrane component.
      Changes in expression of this laminin chain have not been previously associated
      with malignant tumors. Overexpression of laminin alpha4 chain in GBM and
      astrocytoma grade II by gene microarray analysis was confirmed by semiquantitive
      reverse transcription-PCR and immunohistochemistry. Importantly, an alpha4 chain
      containing laminin isoform, laminin-8 (alpha4beta1gamma1), was expressed mainly
      in blood vessel walls of GBMs and histologically normal tissues adjacent to GBMs,
      whereas another alpha4 chain-containing laminin isoform, laminin-9
      (alpha4beta2gamma1), was expressed mainly in blood vessel walls of low-grade
      tumors and normal brain. GBMs that overexpressed laminin-8 had a shorter mean
      time to tumor recurrence (4.3 months) than GBMs with overexpression of laminin-9
      (9.7 months, P = 0.0007). Up-regulation of alpha4 chain-containing laminins could
      be important for the development of glioma-induced neovascularization and glial
      tumor progression. Overexpression of laminin-8 may be predictive of glioma
      recurrence.

PMID- 11454715
TI  - Androgen blocks apoptosis of hormone-dependent prostate cancer cells.
AB  - Androgen plays a critical role in the promotion and growth of prostate cancer.
      Androgen ablation has an expanding role in prostate cancer treatment and is now
      used to improve the efficacy of radiation therapy in addition to its role in
      treatment of metastatic disease. Here we show that androgen interferes with
      induction of prostate cancer cell death induced by a variety of stimuli. The
      effect of androgen on cell death occurs predominantly by interference with
      caspase activation and the inhibition of caspase cleavage in both the extrinsic
      and intrinsic cell death pathways. Androgen inhibited apoptosis induced by both
      tumor necrosis factor alpha (TNF-alpha) and by Fas activation with or without
      concomitant irradiation. An antiapoptotic effect was seen in the presence of
      R1881, dihydrotestosterone, and also 17beta-estradiol within 24 h of death
      induction. Sustained inhibition of apoptosis at 72 h was seen only with R1881,
      dihydrotestosterone, cyproterone acetate, and hydroxyflutamide. Androgen
      treatment inhibited activation of caspases-8, -7, and -9 by TNF-alpha +/-
      irradiation. Androgen attenuated BAX expression and blocked appearance of the
      proapoptotic p18 fragment of BAX. Androgen also abrogated BID cleavage induced by
      TNF-alpha + irradiation that contributed to a decrease in cytochrome c egress
      from mitochondria induced by TNF-alpha +/- irradiation. There was also decreased
      mitochondrial depolarization in response to TNF-alpha + irradiation. Production
      of the proapoptotic lipid metabolite ceramide was not affected by androgen, but
      androgen acted downstream from ceramide generation because R1881 blocked cell
      death induction by bacterial sphingomyelinase. Inhibition of phosphoinositol-3
      kinase activity by wortmannin induced apoptosis that was also blocked by
      androgen, but there was no effect on protein levels or phosphorylation of AKT,
      indicating that R1881 did not interact with survival signaling of phosphoinositol
      3-kinase. Lastly, androgen inhibited activation of nuclear factor-kappaB during
      death induction, but the effect of androgen on cell death was not mediated by
      interference with the nuclear factor-kappaB pathway. The data suggest that
      androgen induced blockade of caspase activation in both intrinsic and extrinsic
      cell death pathways and thereby was able to protect prostate cancer cells from
      apoptosis induced by diverse stimuli.

PMID- 11454716
TI  - Metastasis-inducing dna regulates the expression of the osteopontin gene by
      binding the transcription factor Tcf-4.
AB  - Small 1,000-bp fragments of genomic DNA obtained from human malignant breast
      cancer cell lines when transfected into a benign rat mammary cell line enhance
      transcription of the osteopontin gene and thereby cause the cells to metastasize
      in syngeneic rats. To identify the molecular events underlying this process,
      transient cotransfections of an osteopontin promoter-reporter construct and
      fragments of one metastasis-inducing DNA (Met-DNA) have identified the active
      components in the Met-DNA as the binding sites for the T-cell factor (Tcf) family
      of transcription factors. Incubation of cell extracts with active DNA fragments
      containing the sequence CAAAG caused retardation of their mobilities on
      polyacrylamide gels, and Western blotting identified Tcf-4, beta-catenin, and E
      cadherin in the relevant DNA complexes in vitro. Transfection of an expression
      vector for Tcf-4 inhibited the stimulated activity of the osteopontin promoter
      reporter construct caused by transiently transfected active fragments of Met-DNA
      or permanently transfected Met-DNA. This stimulated activity of the osteopontin
      promoter-reporter construct is accompanied by an increase in endogenous
      osteopontin mRNA but not in fos or actin mRNAs in the transfected cells.
      Permanent transfection of the benign rat mammary cell line with a 20-bp fragment
      from the Met-DNA containing the Tcf recognition sequence CAAAG caused an enhanced
      permanent production of endogenous osteopontin protein in vitro and induced the
      cells to metastasize in syngeneic rats in vivo. The corresponding fragment
      without the CAAAG sequence was without either effect. Therefore, the regulatory
      effect of the C9-Met-DNA is exerted, at least in part, by a CAAAG sequence that
      can sequester the endogenous inhibitory Tcf-4 and thereby promote transcription
      of osteopontin, the direct effector of metastasis in this system.

PMID- 11454717
TI  - Absence of Crabtree effect in human melanoma cells adapted to growth at low pH:
      reversal by respiratory inhibitors.
AB  - Because many tumors are acidic and hypoxic relative to normal tissues, glycolysis
      and oxygen consumption were investigated in early-passage human melanoma cells
      adapted to growth at pH 6.7. In the absence of glucose, the basal rate of oxygen
      consumption in low pH-adapted cells was 75% of that in cells grown at pH 7.3. The
      rate of lactic acid production in low pH-adapted cells was increased 4-fold by
      exposure to 16.7 mM glucose compared with a 10-fold increase in cells grown at pH
      7.3. Furthermore, in low pH-adapted cells the rate of oxygen consumption was
      stimulated by the addition of glucose in contrast to the inhibition of oxygen
      consumption by elevated glucose in cells grown at pH 7.3 (i.e., the Crabtree
      effect). Both low pH-adapted cells and cells grown at pH 7.3 exposed to glucose
      plus 0.35 mM meta-iodo-benzylguanidine (MIBG), an inhibitor of mitochondrial
      respiration, had oxygen consumption reduced by approximately 60% and lactic acid
      production increased by approximately 65% relative to glucose alone. Although
      adaptation to growth at low pH was associated with a loss of the Crabtree effect
      and a higher ratio of oxygen consumption to lactic acid production, the rate of
      glycolysis was the same in both growth conditions in the presence of 0.1 mM
      dinitrophenol, an uncoupler of ATP synthesis. This indicates that the glycolytic
      capacity of low pH-adapted cells remains unchanged. Therefore, tumor acute
      acidification and oxygenation can be achieved by exposure to hyperglycemia
      combined with MIBG to improve therapeutic response.

PMID- 11454718
TI  - Alterations of p14ARF, p53, and p73 genes involved in the E2F-1-mediated
      apoptotic pathways in non-small cell lung carcinoma.
AB  - Overexpression of E2F-1 induces apoptosis by both a p14ARF-p53- and a p73
      mediated pathway. p14ARF is the alternate tumor suppressor product of the
      INK4a/ARF locus that is inactivated frequently in lung carcinogenesis. Because
      p14ARF stabilizes p53, it has been proposed that the loss of p14ARF is
      functionally equivalent to a p53 mutation. We have tested this hypothesis by
      examining the genomic status of the unique exon 1beta of p14ARF in 53 human cell
      lines and 86 primary non-small cell lung carcinomas and correlated this with
      previously characterized alterations of p53. Homozygous deletions of p14ARF were
      detected in 12 of 53 (23%) cell lines and 16 of 86 (19%) primary tumors. A single
      cell line, but no primary tumors, harbored an intragenic mutation. The deletion
      of p14ARF was inversely correlated with the loss of p53 in the majority of cell
      lines (P = 0.02), but this relationship was not maintained among primary tumors
      (P = 0.5). E2F-1 can also induce p73 via a p53-independent apoptotic pathway.
      Although we did not observe inactivation of p73 by either mutation or DNA
      methylation, haploinsufficiency of p73 correlated positively with either p14ARF
      or p53 mutation or both (P = 0.01) in primary non-small cell lung carcinomas.
      These data are consistent with the current model of p14ARF and p53 interaction as
      a complex network rather than a simple linear pathway and indicate a possible
      role for an E2F-1-mediated failsafe, p53-independent, apoptotic pathway involving
      p73 in human lung carcinogenesis.

PMID- 11454719
TI  - The Src-suppressed C kinase substrate, SSeCKS, is a potential metastasis
      inhibitor in prostate cancer.
AB  - The molecular mechanisms leading to prostate cancer remain poorly understood,
      especially concerning the progression to the metastatic form. SSeCKS, a major
      protein kinase C substrate with tumor suppressor activity, is likely the rodent
      orthologue of human Gravin/AKAP12, a scaffolding protein for protein kinases A
      and C. Gravin was mapped as a single-copy gene to 6q24-25.2, a hotspot for
      deletion in advanced prostate cancer, and therefore, we investigated the role of
      SSeCKS/Gravin in prostate oncogenesis. SSeCKS/Gravin protein was detected in
      untransformed rat and human prostate epithelial cell lines EP12 and PZ-HPV-7,
      respectively, and in human prostatic epithelium, especially basal epithelial
      cells. In contrast, SSeCKS/Gravin protein and RNA levels were severely reduced in
      human (PC-3, PPC-1, LNCaP, DU145, and TSU) and rat Dunning (AT3.1 and MatLyLu)
      prostate cancer cell lines. The regulated reexpression of SSeCKS in MatLyLu cells
      induced filopodia-like projections and a decrease in anchorage-independent
      growth. In nude mice, SSeCKS reexpression slightly decreased primary-site tumor
      growth but severely decreased the formation of lung metastases. Primary-site
      tumors that progressed lost regulated SSeCKS reexpression. SSeCKS/Gravin
      expression was detected in benign human prostatic lesions and well-differentiated
      carcinomas but not in undifferentiated lesions with Gleason sums > or =6. Our
      data suggest a role for the loss of SSeCKS/Gravin in the metastatic progression
      of human prostate cancer.

PMID- 11454720
TI  - Prostate cancer cells induce osteoblast differentiation through a Cbfa1-dependent
      pathway.
AB  - Metastases from prostatic adenocarcinoma (prostate cancer) are characterized by
      their predilection for bone and typical osteoblastic features. An in vitro model
      of bone metastases from prostate cancer was developed using a bicompartment
      coculture system of mouse osteoblasts and human prostate cancer cells. In this
      model, the bone-derived prostate cancer cell lines MDA PCa 2a and MDA PCa 2b
      induced a specific and reproducible increase in osteoblast proliferation.
      Moreover, these cells were able to induce osteoblast differentiation, as assessed
      by increased alkaline phosphatase activity, Osteocalcin expression, and calcified
      matrix formation. This osteoblastic reaction was confirmed in vivo by
      intrafemoral injection of MDA PCa 2b cells into severe combined immunodeficiency
      disease mice. In contrast, the highly undifferentiated, bone-derived human
      prostate cancer cell line PC3 did not produce an osteoblastic reaction in vitro
      and induced osteolytic lesions in vivo. The osteoblast differentiation induced by
      MDA PCa 2b cells was associated with up-regulation of the osteoblast-specific
      transcriptor factor Cbfa1. Moreover, treatment of osteoblasts with conditioned
      medium obtained from MDA PCa 2b cells resulted in up-regulation of Cbfa1 and
      Osteocalcin expression. In support of the differentiation studies, a microarray
      analysis showed that primary mouse osteoblasts grown in the presence of MDA PCa
      2b cells showed a shift in the pattern of gene expression with an increase in
      mRNA-encoding Procollagen type I and Osteopontin and a decrease in mRNA-encoding
      proteins associated with myoblast differentiation, namely myoglobin and myosin
      light-chain 2. Taken together, these findings suggest that the bone-derived
      prostate cancer cells MDA PCa 2a and MDA PCa 2b promote differentiation of
      osteoblast precursors to an osteoblastic phenotype through a Cbfa1-dependent
      pathway. These results also established that soluble factors produced by prostate
      cancer cells can induce expression of osteoblast-specific genes. This in vitro
      model provides a valuable system to isolate molecules secreted by prostate cancer
      cells that favor osteoblast differentiation. Moreover, it allows to screen for
      therapeutic agents blocking the osteoblast response to prostate cancer.

PMID- 11454721
TI  - Correspondence re: B. H. Joshi et al., interleukin-13 receptor alpha chain: a
      novel tumor-associated transmembrane protein in primary explants of human
      malignant gliomas. Cancer Res., 60: 1168-1172, 2000.

PMID- 11454723
TI  - The use of a high-volume screening procedure to assess the effects of dietary
      flavonoids on human cyp1a1 expression.
AB  - We examined the effects of several agents, including dietary flavonoids, on
      CYP1A1 expression utilizing a recently developed high-throughput screening system
      for assessing human cytochrome P450 (CYP) induction. HepG2 cells, stably
      integrated with regulatory regions of human CYP1A1, were treated with
      resveratrol, apigenin, curcumin, kaempferol, green tea extract (GTE), (-)
      epigallocatechin gallate (EGCG), quercetin, and naringenin. Of these flavonoids,
      resveratrol produced the greatest increase in CYP1A1-mediated luciferase activity
      (10-fold), whereas GTE, apigenin, curcumin, and kaempferol produced 2- to 3-fold
      increases in activity. Compared with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
      omeprazole, or benzanthracene, where increases in luciferase activity ranged from
      12- to 35-fold, these flavonoids exhibited weak agonist activity. The remaining
      compounds, EGCG, quercetin, and naringenin, produced negligible effects.
      Cotreatment of cells with TCDD and GTE, naringenin, and apigenin resulted in 58,
      77, and 74% reductions, respectively, in TCDD-mediated CYP1A1 induction,
      indicating that these flavonoids exhibit potential antagonist activity toward the
      aryl hydrocarbon (Ah) receptor. Furthermore, results also suggest that GTE and
      apigenin possess Ah receptor antagonist and weak agonist activities. Thus, we
      have shown that a 96-well plate assay allowing high-throughput screening for P450
      induction in less than 24 h was efficient in determining the effects of
      flavonoids on human CYP1A expression. Signal-to-noise ratios were low, and well
      to-well and replicate variability was below 10%, allowing induction to be easily
      detected in this system. These features illustrate the reliability and
      feasibility of this high-volume screening system for identifying CYP inducers.
      Furthermore, results produced with the stable cell line were corroborated in
      HepG2 cells and primary cultures of human hepatocytes, suggesting that stably
      integrated cell lines harboring enhancer elements of P450 genes may be highly
      conducive to high-throughput screening.

PMID- 11454724
TI  - Evaluation of the interaction of loratadine and desloratadine with P
      glycoprotein.
AB  - The absorption of many drugs is affected by their interaction with ATP-binding
      cassette (ABC) transporters. The most extensively studied of these ABC
      transporters is the proein product of MDR1 (multidrug resistance) that encodes a
      170-kDa integral plasma membrane phosphorylated glycoprotein known as P
      glycoprotein (P-gp). The purpose of this study was to determine, using two
      different methods, whether the nonsedating antihistamine loratadine (L) and its
      active metabolite desloratadine (DL) interact with P-gp. MDR cells presenting
      human P-gp were incubated with the fluorescent P-gp substrate daunorubicin with
      or without L, DL, and several positive controls. The IC(50) of loratadine
      (approximately 11 microM) was approximately 160 times the maximum observed plasma
      concentration (C(max)) following a dose of 10 mg. The IC(50) of desloratadine
      (approximately 43 microM) was approximately 880 times the C(max) following a dose
      of 5 mg. The positive control, cyclosporin A, had an IC(50) of approximately 1
      microM. ATP hydrolysis activity was measured in the membrane fraction prepared
      from MDR cells presenting P-gp, which were exposed to various concentrations of
      test compounds. Known substrates of P-gp demonstrated clear, repeatable,
      concentration-dependent increases in ATP hydrolysis activity. L caused an
      increase in ATPase activity above basal levels. L had a V(max) about 200% basal
      activity and K(m) of approximately 3 microM for P-gp. In contrast, DL had no
      significant effect on baseline ATP hydrolysis. L inhibited human P-gp much less
      than verapamil or cyclosporin A. DL inhibited human P-gp significantly less than
      L (4 times). DL therefore is not a significant inhibitor of P-gp and should not
      cause clinical drug interactions with agents that are P-gp substrates.

PMID- 11454725
TI  - Bisphenol a glucuronide, a major metabolite in rat bile after liver perfusion.
AB  - The environmental estrogen bisphenol A, orally introduced into the body, passes
      through the liver and modulates the endocrine system to elicit irreversible
      changes in the functioning of reproduction. To elucidate the actual and dynamic
      metabolism of bisphenol A in the liver before its arrival at target organs, this
      study evaluated the metabolism and disposition of the compound within the passage
      through the liver in Sprague-Dawley rats. On perfusion of 7.5 micromol of
      bisphenol A into the liver via the portal vein, approximately 91% of the infused
      bisphenol A was absorbed by the liver tissue, and about 65% of the absorbed
      bisphenol A was glucuronidated within 60 min. Roughly 65% of the bisphenol A
      glucuronide that formed in the liver was excreted into the bile and about 35%
      into the hepatic vein. On perfusion of 0.01, 0.05, and 0.1 mM bisphenol A
      solution into the liver, free bisphenol A was excreted only into the vein at 5.6,
      9.3, and 14.6%, respectively, of the total bisphenol A. These results suggest
      that most bisphenol A absorbed by the intestine is probably glucuronidated
      exclusively in the liver and the conjugate is excreted mainly into the bile.

PMID- 11454726
TI  - Cytochrome P4502E1 induction increases thioacetamide liver injury in diet
      restricted rats.
AB  - Earlier studies have shown highly exaggerated mechanism-based liver injury of
      thioacetamide (TA) in rats following moderate diet restriction (DR) and in
      diabetes. The objective of the present study was to investigate the mechanism of
      higher liver injury of TA in DR rats. Since both DR and diabetes induce CYP2E1,
      we hypothesized that hepatic CYP2E1 plays a major role in the bioactivation-based
      liver injury of TA. When male Sprague-Dawley rats (250-275 g) were maintained on
      diet restriction (DR, 35% of ad libitum fed rats, 21 days) the total hepatic
      microsomal cytochrome P450 (CYP450) was increased 2-fold along with a 4.6-fold
      increase in CYP2E1 protein, which corresponded with a 3-fold increase in CYP2E1
      activity as measured by chlorzoxazone hydroxylation. To further test the
      involvement of CYP2E1, 24 and 18 h after pretreatment with pyridine (PYR) and
      isoniazid (INZ), specific inducers of CYP2E1, male Sprague-Dawley rats received a
      single administration of 50 mg of TA/kg (i.p.). TA liver injury was >2.5- and >3
      fold higher at 24 h in PYR + TA and INZ + TA groups, respectively, compared with
      the rats receiving TA alone. Pyridine pretreatment resulted in significantly
      increased total CYP450 content accompanied by a 2.2-fold increase in CYP2E1
      protein and 2-fold increase in enzyme activity concordant with increased liver
      injury of TA, suggesting mechanism-based bioactivation of TA by CYP2E1. Hepatic
      injury of TA in DR rats pretreated with diallyl sulfide (DAS), a well known
      irreversible in vivo inhibitor of CYP2E1, was significantly decreased (60%) at 24
      h. CCl(4) (4 ml/kg i.p.), a known substrate of CYP2E1, caused lower liver injury
      and higher animal survival confirming inhibition of CYP2E1 by DAS pretreatment.
      The role of flavin-containing monooxygenase (FMO) in TA bioactivation implicated
      by previous in vitro studies, and consequent increased TA-induced liver injury in
      DR rats was tested in vivo with a relatively selective inhibitor of FMO, indole-3
      carbinol, and then treated with 50 mg of TA/kg. FMO activity and alanine
      aminotransferase levels measured at different time points revealed that TA liver
      injury was not decreased although FMO activity was significantly decreased,
      suggesting that hepatic FMO is unlikely to bioactivate TA. These findings suggest
      induction of CYP2E1 as the primary mechanism of increased bioactivation-based
      liver injury of TA in DR rats.

PMID- 11454727
TI  - Glucuronidation of 1-hydroxypyrene by human liver microsomes and human UDP
      glucuronosyltransferases UGT1A6, UGT1A7, and UGT1A9: development of a high
      sensitivity glucuronidation assay for human tissue.
AB  - Human UDP-glucuronosyltransferases (UGT, EC 2.4.1.17) involved in the
      biotransformation of pyrene were investigated by a sensitive fluorometric high
      performance liquid chromatography (HPLC)method developed for determining
      activities toward 1-hydroxypyrene. The endpoint metabolite of pyrene, 1
      pyrenylglucuronide, is a well-known urinary biomarker for the assessment of human
      exposure to polycyclic aromatic hydrocarbons. 1-Pyrenylglucuronide was
      synthesized using rat liver microsomes as biocatalyst. The yield was
      satisfactory, 22%. 1-Pyrenylglucuronide, identified by (1)H NMR and by
      electrospray mass spectrometry, was used for method validation and calibration.
      The HPLC assay was very sensitive with a quantitation limit of 3 pg (8 fmol) for
      1-pyrenylglucuronide. The assay was precise, showing a relative standard
      deviation of 5% or less at 0.1 to 300 microM 1-hydroxypyrene. Only 2 microg of
      microsomal protein was required for the assay in human liver. The glucuronidation
      of 1-hydroxypyrene was catalyzed at high rates in microsomes from pooled or three
      individual liver samples, showing comparable apparent K(m) values. The formation
      of 1-pyrenylglucuronide was catalyzed by recombinant human UGT1A6, UGT1A7, and
      UGT1A9, the K(m) values being 45, 12, and 1 microM, respectively. The apparent
      K(m) values in human liver microsomes, ranging from 6.9 to 8.6 microM, agreed
      well with these results. The method provides a sensitive tool for measuring
      extremely low UGT activities and a specific means for assessing interindividual
      differences in 1-hydroxypyrene-metabolizing UGT activities in human liver and
      other tissues.

PMID- 11454728
TI  - Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating
      biotransformation, inhibitory effects, and comparison to R-citalopram.
AB  - Transformation of escitalopram (S-CT), the pharmacologically active S
      enantiometer of citalopram, to S-desmethyl-CT (S-DCT), and of S-DCT to S
      didesmethyl-CT (S-DDCT), was studied in human liver microsomes and in expressed
      cytochromes (CYPs). Biotransformation of the R-enantiomer (R-CT) was studied in
      parallel. S-CT was transformed to S-DCT by CYP2C19 (K(m) = 69 microM), CYP2D6
      (K(m) = 29 microM), and CYP3A4 (K(m) = 588 microM). After normalization for
      hepatic abundance, relative contributions to net intrinsic clearance were 37% for
      CYP2C19, 28% for CYP2D6, and 35% for CYP3A4. At 10 microM S-CT in liver
      microsomes, S-DCT formation was reduced to 60% of control by 1 microM
      ketoconazole, and to 80 to 85% of control by 5 microM quinidine or 25 microM
      omeprazole. S-DDCT was formed from S-DCT only by CYP2D6; incomplete inhibition by
      quinidine in liver microsomes indicated participation of a non-CYP pathway. Based
      on established index reactions, S-CT and S-DCT were negligible inhibitors (IC(50)
      > 100 microM) of CYP1A2, -2C9, -2C19, -2E1, and -3A, and weakly inhibited CYP2D6
      (IC(50) = 70-80 microM). R-CT and its metabolites, studied using the same
      procedures, had properties very similar to those of the corresponding S
      enantiomers. Thus S-CT, biotransformed by three CYP isoforms in parallel, is
      unlikely to be affected by drug interactions or genetic polymorphisms. S-CT and S
      DCT are also unlikely to cause clinically important drug interactions via CYP
      inhibition.

PMID- 11454729
TI  - Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl
      isothiocyanate.
AB  - The inhibition and mechanism-based inactivation potencies of phenethyl
      isothiocyanate (PEITC) for human cytochrome P450 (CYP) activities were
      investigated using microsomes from baculovirus-infected insect cells expressing
      specific human CYP isoforms. PEITC competitively inhibited phenacetin O
      deethylase activity catalyzed by CYP1A2 (K(i) = 4.5 +/- 1.0 microM) and coumarin
      7-hydroxylase activity catalyzed by CYP2A6 (K(i) = 18.2 +/- 2.5 microM).
      Benzyloxyresorufin O-dealkylase activity catalyzed by CYP2B6 was most strongly
      and noncompetitively inhibited (K(i) = 1.5 +/- 0.0 microM). Paclitaxel 6alpha
      hydroxylase activity catalyzed by CYP2C8 was not affected by PEITC up to 100
      microM. PEITC noncompetitively inhibited S-warfarin 7-hydroxylase activity
      catalyzed by CYP2C9 (K(i) = 6.5 +/- 0.9 microM), S-mephenytoin 4'-hydroxylase
      activity catalyzed by CYP2C19 (K(i) = 12.0 +/- 3.2 microM), bufuralol 1'
      hydroxylase activity catalyzed by CYP2D6 (K(i) = 28.4 +/- 7.9 microM), and
      chlorzoxazone 6-hydroxylase activity catalyzed by CYP2E1 (K(i) = 21.5 +/- 3.4
      microM). The inhibition for testosterone 6beta-hydroxylase activity catalyzed by
      CYP3A4 was a mixed-type of competitive (K(i) = 34.0 +/- 6.5 microM) and
      noncompetitive (K(i) = 63.8 +/- 12.5 microM) inhibition. Furthermore, PEITC is a
      mechanism-based inactivator of human CYP2E1. The k(inact) value was 0.339 min(-1)
      and K(i) was 9.98 microM. Human CYP1A2, CYP2A6, CYP2B6, CYP2D6, and CYP3A4 were
      not inactivated. The present study directly proved that the chemopreventive
      effects of PEITC for nitrosamine-induced carcinogenesis are due to the inhibition
      of CYP by an in vitro study. The possibility that PEITC would affect the
      pharmacokinetics of clinically used drugs that are metabolized by these CYP
      isoforms was also suggested.

PMID- 11454730
TI  - Carbinolamines, imines, and oxazolidines from fluorinated propranolol analogs.
      (19)F NMR and mass spectral characterization and evidence for formation as
      intermediates in cytochrome P450-catalyzed N-dealkylation.
AB  - Formation of carbinolamine, imine, and oxazolidines from the reactions of
      desisopropylpropranolol (5), its O-methyl ether (10), and 3-(1
      naphthoxy)propylamine (11) with trifluoroacetone and trifluoroacetaldehyde methyl
      hemiacetal was investigated by (19)F NMR and tandem mass spectrometry. Products
      from the metabolism of the related secondary amine substrates
      trifluoropropranolol (7), its O-methyl ether (23), and its N-trifluoroethyl-O
      methyl ether analog (24) in the presence of rat liver microsomes and CYP1A2 were
      examined to determine whether these species were formed. The (19)F NMR
      experiments showed the presence of carbinolamine and imine species from these
      primary amines and fluorinated carbonyl compounds in solution. Mass spectral
      experiments under atmospheric pressure chemical ionization and electrospray
      ionization-ion trap conditions showed formation of imine metabolites (and/or
      oxazolidine from 7) as well as products of N-dealkylation and aromatic
      hydroxylation when the secondary amine substrates were incubated with rat liver
      microsomes or CYP1A2. In spite of mass spectral evidence for these imines as
      metabolites, we were unable to detect the carbinolamines under the conditions
      used in these studies. Their presence is inferred from the results of the (19)F
      NMR experiments.

PMID- 11454731
TI  - Evaluation of the contribution of cytochrome P450 3A4 to human liver microsomal
      bupropion hydroxylation.
AB  - The purpose of this investigation was to evaluate the role of cytochrome P450
      (CYP) 3A4 in human liver microsomal bupropion (BUP) hydroxylation. Across the BUP
      concentration range of 0.075 to 12 mM, cDNA-expressed CYP3A4 demonstrated BUP
      hydroxylase activity only when incubated with concentrations > or =4 mM. When
      assayed at 12 mM BUP, cDNA-expressed CYP3A4 catalyzed BUP hydroxylation at a 30
      fold lower rate than cDNA-expressed CYP2B6 (0.2 versus 7 pmol/min/pmol of P450).
      Among a panel of 16 human liver microsomes (HLMs), BUP hydroxylase activity
      varied 80-fold when assayed at 500 microM and did not strongly correlate with
      testosterone 6beta-hydroxylase activity when assayed at 250 microM testosterone
      (r(2) = 0.39), nor with CYP3A4 protein expression. A selective CYP3A4 inhibitor,
      troleandomycin (TAO), did not significantly alter rates of BUP hydroxylation when
      assayed in a moderate activity HLM at 10 to 2000 microM BUP, as reflected by a
      similarity in the kinetic parameters of BUP hydroxylation in the absence or
      presence of TAO. In addition, the same range of TAO concentrations (0.025-100
      microM) that inhibited testosterone 6beta-hydroxylation in a concentration
      dependent manner (46-81%) in pooled HLMs produced negligible inhibition (7%) of
      BUP hydroxylation when assayed at 500 microM BUP. These results suggest that
      CYP3A4 does not significantly catalyze BUP hydroxylation. Furthermore, these
      results complement recent data supporting selectivity of BUP hydroxylation for
      CYP2B6 at 500 microM BUP.

PMID- 11454732
TI  - Transcriptional regulation of rat hepatic aryl sulfotransferase (SULT1A1) gene
      expression by glucocorticoids.
AB  - The 5'-flanking region [1892 base pairs (bp)] of the rat aryl sulfotransferase
      (SULT1A1) gene was cloned and the cis-acting sequences involved in glucocorticoid
      inducible SULT1A1 gene transcription were characterized. SULT1A1 promoter and 5'
      flanking sequences lacked a TATA box and a consensus glucocorticoid response
      element. Using a 5'-rapid amplification of cDNA ends approach, four SULT1A1
      transcription start sites were identified. Transient transfection studies with
      SULT1A1-5':luciferase reporter constructs in primary cultured rat hepatocytes
      revealed that treatment with the potent glucocorticoid dexamethasone (10(-9)-10(
      5) M) produced concentration-dependent increases in luciferase activity in
      constructs containing from 1892 to 119 bp of the SULT1A1 5'-flanking region.
      Relative to the most upstream SULT1A1 transcription start site, the minimal cis
      acting sequences that were required for dexamethasone-inducible SULT1A1
      expression were located between -84 and -69 bp. Treatment of transfectants with a
      panel of steroids, including dexamethasone, triamcinolone acetonide,
      hydrocortisone, dihydrotestosterone, 17beta-estradiol, and pregnenolone-16alpha
      carbonitrile, revealed that steroid-inducible SULT1A1 gene expression was
      specific for glucocorticoid-class steroids. Concentration-response studies,
      coupled with a robust inhibition of glucocorticoid-inducible SULT1A1
      5':luciferase reporter activity by antiglucocorticoid/antiprogestin RU-486,
      recapitulated earlier findings on endogenous SULT1A1 gene expression and
      implicated a major role for the glucocorticoid receptor transcription factor in
      the regulation of glucocorticoid-inducible SULT1A1 gene expression.

PMID- 11454733
TI  - Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose
      of [(14)C]linezolid to healthy human subjects.
AB  - Linezolid (Zyvox), the first of a new class of antibiotics, the oxazolidinones,
      is approved for treatment of Gram-positive bacterial infections, including
      resistant strains. The disposition of linezolid in human volunteers was
      determined, after a 500-mg (100-microCi) oral dose of [(14)C]linezolid.
      Radioactive linezolid was administered as a single dose, or at steady-state on
      day 4 of a 10-day, 500-mg b.i.d. regimen of unlabeled linezolid (n =
      4/sex/regimen). Mean recovery of radioactivity in excreta was 93.8 +/- 1.1%
      (range 91.2-95.2%, n = 15), of which 83.9 +/- 3.3% (range 76.7-88.4%) was in
      urine and 9.9 +/- 3.4% (range 5.3-16.9%) was in feces. There was no major
      difference in rate or route of excretion of radioactivity by dose regimen.
      Linezolid was excreted primarily intact, and as two inactive, morpholine ring
      oxidized metabolites, PNU-142586 and PNU-142300. Other minor metabolites were
      characterized by high-performance liquid chromatography-atmospheric pressure
      chemical ionization-mass spectrometry and (19)F NMR spectroscopy. After the
      single radioactive dose, linezolid was the major circulating drug-related
      material accounting for about 78% (male) and 93% (female) of the radioactivity
      area under the curve (AUC). PNU-142586 (T(max) of 3-5 h) accounted for about 26%
      (male) and 9% (female) of the radioactivity AUC. PNU-142300 (T(max) of 2-3 h)
      accounted for about 7% (male) and 4% (female) of the radioactivity AUC. Overall,
      mean linezolid and PNU-142586 exposures at steady-state were similar across sex.
      In conclusion, linezolid circulates in plasma mainly as parent drug. Linezolid
      and two major, inactive metabolites account for the major portion of linezolid
      disposition, with urinary excretion representing the major elimination route.
      Formation of PNU-142586 was the rate-limiting step in the clearance of linezolid.

PMID- 11454734
TI  - Identification of cytochrome P-450 isoforms responsible for cis-tramadol
      metabolism in human liver microsomes.
AB  - The metabolism of cis-tramadol has been studied in human liver microsomes and in
      cDNA-expressed human cytochrome P-450 (CYP) isoforms. Human liver microsomes
      catalyzed the NADPH-dependent metabolism of tramadol to the two primary tramadol
      metabolites, namely, O-desmethyl-tramadol (metabolite M1) and N-desmethyl
      tramadol (metabolite M2). In addition, tramadol was also metabolized to two minor
      secondary metabolites (each comprising < or =3.0% of total tramadol metabolism),
      namely, N,N-didesmethyl-tramadol (metabolite M3) and N,O-didesmethyl-tramadol
      (metabolite M5). Kinetic analysis revealed that multiple CYP enzymes were
      involved in the metabolism of tramadol to both M1 and M2. For the high-affinity
      enzymes involved in M1 and M2 formation, K(m) values were 116 and 1021 microM,
      respectively. Subsequent reaction phenotyping studies were performed with a
      tramadol substrate concentration of 250 microM. In studies with characterized
      human liver microsomal preparations, good correlations were observed between
      tramadol metabolism to M1 and M2 and enzymatic markers of CYP2D6 and CYP2B6,
      respectively. Tramadol was metabolized to M1 by cDNA-expressed CYP2D6 and to M2
      by CYP2B6 and CYP3A4. Tramadol metabolism in human liver microsomes to M1 and M2
      was markedly inhibited by the CYP2D6 inhibitor quinidine and the CYP3A4 inhibitor
      troleandomycin, respectively. In summary, this study demonstrates that cis
      tramadol can be metabolized to tramadol metabolites M1, M2, M3, and M5 in human
      liver microsomal preparations. By kinetic analysis and the results of the
      reaction phenotyping studies, tramadol metabolism in human liver is catalyzed by
      multiple CYP isoforms. Hepatic CYP2D6 appears to be primarily responsible for M1
      formation, whereas M2 formation is catalyzed by CYP2B6 and CYP3A4.

PMID- 11454735
TI  - Inhibition of rat liver microsomal CYP1A2 and CYP2B1 activity by N-(2-heptyl)-N
      methyl-propargylamine and by N-(2-heptyl)-propargylamine.
AB  - (R)-N-(2-Heptyl)-N-methyl-propargylamine (R-2HMP) and (R)-N-(2-heptyl)
      propargylamine (R-2HPA) are analogs of R-deprenyl. R-Deprenyl, a selective
      monoamine oxidase B inhibitor, is a mechanism-based inactivator of purified
      CYP2B1. The aim of the present study was to determine whether R-2HMP and R-2HPA
      behaved like deprenyl with respect to inhibiting cytochrome P450 (CYP450) enzyme
      activity. The activities of CYP1A2 and CYP1A1 were assessed by measuring the
      deethylation of 7-ethoxyresorufin by liver microsomes obtained from control and
      beta-naphthoflavone-treated female Wistar rats, respectively. CYP2B1 activity was
      assessed by measuring depentylation of 7-pentoxyresorufin by liver microsomes
      obtained from phenobarbital-treated rats. The activity of CYP1A1 was unaffected
      by 100 microM concentrations of R-deprenyl, R-2HMP, or R-2HPA. In contrast, the
      activities of CYP1A2 and CYP2B1 were significantly decreased. In general, the
      percentage of CYP1A2 activity remaining in the presence of 100 microM of one of
      these propargylamines ranged from 45 to 56%, whereas 10% or less of CYP2B1
      activity remained. No marked differences between the various propargylamines were
      observed. The IC(50) values for the inhibition of CYP2B1 activity by R-deprenyl,
      R-2HMP, and R-2HPA were found to be 2.6, 8.5, and 3.6 microM, respectively. The S
      enantiomers of deprenyl, 2HMP, and 2HPA also inhibited the activity of microsomal
      CYP2B1. R-2HMP, R-2HPA, and S-2HPA were found to be mechanism-based inactivators
      of CYP2B1 activity. The inactivation constants k(inact) and K(I) were found to be
      as follows: R-deprenyl, 1.3 microM and 0.32 min(-1); R-2HMP, 0.8 microM and 0.08
      min(-1); R-2HPA, 0.5 microM and 0.36 min(-1); and S-2HPA, 0.24 microM and 0.18
      min(-1).

PMID- 11454736
TI  - Biotransformation, excretion kinetics, and tissue distribution of an N
      pyrrolo[1,2-c]imidazolylphenyl sulfonamide herbicide in rats.
AB  - TY029, an N-pyrrolo[1,2-c]imidazolylphenyl sulfonamide herbicide, controls
      economically important weeds through inhibition of protoporphyrinogen oxygenase.
      Due to the potential for exposure to this compound in food and animal feed items,
      a rat metabolism study was required to define the biotransformation of this
      compound. Animals were exposed to single 50- and 2-mg/kg doses of TY029
      [hydantoin-5-(14)C] by oral gavage. About 90% of the administered dose was
      excreted within 96 h after oral administration. Excretion plateaued after 48 h,
      and the cumulative sum of urinary or fecal excretion after 48 h was less than 5%
      of the orally administered dose. TY029 yielded seven major metabolites. While
      some metabolites were formed by epimerization around chiral centers, others were
      generated through hydrolytic bond cleavage and hydroxylations and subsequent
      oxidation of hydroxyl groups to carboxylic acids. One metabolite, about 6.1% of
      the dose, was observed only in the urine from low-dose female rats. This
      metabolite was characterized as a glutamate conjugate of an extensively oxidized
      analog of TY029. With the exception of the glutamate conjugate, the same
      metabolites were observed in the excreta of all dose groups. However, the
      relative ratios of the metabolites were different between various dose groups.

PMID- 11454737
TI  - Aneuploid colon cancer cells have a robust spindle checkpoint.
AB  - Colon cancer cells frequently display minisatellite instability (MIN) or
      chromosome instability (CIN). While MIN is caused by mismatch repair defects, the
      lesions responsible for CIN are unknown. The observation that CIN cells fail to
      undergo mitotic arrest following spindle damage suggested that mutations in
      spindle checkpoint genes may account for CIN. However, here we show that CIN
      cells do undergo mitotic arrest in response to spindle damage. Although the
      maximum mitotic index achieved by CIN lines is diminished relative to MIN lines,
      CIN cells clearly have a robust spindle checkpoint. Consistently, mutations in
      spindle checkpoint genes are rare in human tumours. In contrast, the adenomatous
      polyposis coli (APC) gene is frequently mutated in CIN cells. Significantly, we
      show here that expression of an APC mutant in MIN cells reduces the mitotic index
      following spindle damage to a level observed in CIN cells, suggesting that APC
      dysfunction may contribute to CIN.

PMID- 11454738
TI  - Hypoxia-inducible factor-1 alpha (HIF-1 alpha) escapes O(2)-driven proteasomal
      degradation irrespective of its subcellular localization: nucleus or cytoplasm.
AB  - Eukaryotic cells sense oxygen and adapt to hypoxia by regulating a number of
      genes. Hypoxia-inducible factor 1 (HIF-1) is the 'master' in this pleiotypic
      response. HIF-1 comprises two members of the basic helix--loop--helix
      transcription factor family, HIF-1 alpha and HIF-1 beta. The HIF-1 alpha protein
      is subject to drastic O(2)-dependent proteasomal control. However, the signalling
      components regulating the 'switch' for 'escaping' proteasomal degradation under
      hypoxia are still largely unknown. The rapid nuclear translocation of HIF-1 alpha
      could represent an efficient way to escape from this degradation. We therefore
      asked, where in the cell is HIF-1 alpha degraded? To address this question, we
      trapped HIF-1 alpha either in the cytoplasm, by fusing HIF-1 alpha to the
      cytoplasmic domain of the Na(+)-H(+) exchanger (NHE-1), or in the nucleus, by
      treatment with leptomycin B. Surprisingly, we found that HIF-1 alpha is
      stabilized by hypoxia and undergoes O(2)-dependent proteasomal degradation with
      an identical half-life (5--8 min) in both cellular compartments. Therefore, HIF-1
      alpha entry into the nucleus is not, as proposed, a key event that controls its
      stability. This result markedly contrasts with the mechanism that controls p53
      degradation via MDM2.

PMID- 11454739
TI  - Species-specific organization of CpG island promoters at mammalian homologous
      genes.
AB  - An essential issue derived from the sequencing of the human and other genomes is
      the identification of gene regulatory elements. Using in vivo footprinting and
      expression analysis, here we show that mouse and human CpG island promoters at
      homologous genes have a completely different organization in terms of size and
      binding of transcription factors. Despite these species-specific differences, a
      unifying picture emerges from the precise confinement of protein--DNA
      interactions between the 5' boundary of the CpG islands and the transcription
      initiation site. This finding allows direct localization of promoters on genomic
      sequences and reveals a very high rate of variation and evolutionary divergence
      of mammalian regulatory regions. Our results also show that CpG island promoters
      associated with tissue-specific genes, such as the human alpha-globin, are bound
      by ubiquitous factors that allow a constitutive low level of expression in many
      cell types.

PMID- 11454740
TI  - The solution structure of PapGII from uropathogenic Escherichia coli and its
      recognition of glycolipid receptors.
AB  - Uropathogenic Escherichia coli (UPEC) is the primary cause of symptomatic urinary
      tract infection. The P-pili, a bacterial surface organelle, mediates the
      bacterial host--cell adhesion. The PapG adhesin has generated much interest in
      recent years, not only because of its clinical value, i.e. in the prevention of
      microbial adherence, but also because of its ability to promote virulence. Using
      multidimensional nuclear magnetic resonance (NMR) and deuteration we have
      determined the solution structure of the adhesin domain from PapGII (PapGII-198).
      The novel structure of PapGII-198 is composed of a large elongated jellyroll
      motif. Despite an automated search of the structural database failing to reveal
      any similar proteins, PapGII adhesin shares some structural similarities with
      FimH. Furthermore, interpretation of NMR-titration data has enabled us to
      identify the putative binding site for the globoseries of oligosaccharides. This
      work provides insight into UPEC pathogenesis as well as aiding the development of
      preventative therapies and the guidance of future mutagenesis programmes.

PMID- 11454741
TI  - Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin
      coated vesicle uncoating.
AB  - Synaptic vesicle biogenesis involves the recycling of synaptic vesicle components
      by clathrin-mediated endocytosis from the presynaptic membrane. stoned B, a
      protein encoded by the stoned locus in Drosophila melanogaster has been shown to
      regulate vesicle recycling by interacting with synaptotagmin. We report here the
      identification and characterization of a human homolog of stoned B (hStnB). Human
      stoned B is a brain-specific protein which co-enriches with other endocytic
      proteins such as AP-2 in a crude synaptic vesicle fraction and at nerve
      terminals. A domain with homology to the medium chain of adaptor complexes binds
      directly to both AP-2 and synaptotagmin and competes with AP-2 for the same
      binding site within synaptotagmin. Finally we show that the mu 2 homology domain
      of hStnB stimulates the uncoating of both clathrin and AP-2 adaptors from
      clathrin-coated vesicles. We hypothesize that hStnB regulates synaptic vesicle
      recycling by facilitating vesicle uncoating.

PMID- 11454742
TI  - Metaxin is required for tumor necrosis factor-induced cell death.
AB  - We used retrovirus insertion-mediated random mutagenesis and tumor necrosis
      factor (TNF) selection to generate TNF-resistant lines from L929 cells. The
      metaxin gene, which encodes a protein located on the outer membrane of
      mitochondria, was identified to be the gene disrupted in one of the resistant
      lines. The requirement of metaxin in TNF-induced cell death of L929 was confirmed
      by the restoration of TNF sensitivity after ectopic reconstitution of metaxin
      expression. Analysis of the cell death induced by other stimuli revealed that
      metaxin deficiency-mediated death resistance was selective to certain stimuli.
      Studies using deletion mutants of metaxin showed that mitochondrial association
      of metaxin is required for the function of metaxin. Over-expression of truncated
      metaxin lacking the mitochondria anchoring sequence mimicked metaxin deficiency
      in wild-type cells. Interfering with metaxin prevented TNF-induced necrotic cell
      death in L929 cells and apoptosis in MCF-7 cells. Our work has thus defined a
      novel component in the death pathway used by TNF and some other death stimuli.

PMID- 11454743
TI  - A genetic look at the active site of RNA polymerase III.
AB  - rpc160-112, a mutant of the RNA polymerase III active site, is corrected in vivo
      by six second-site mutants obtained by random mutagenesis. These mutants
      introduce single-site amino acid replacements at the two large subunits of the
      enzyme. The mutated motifs are conserved in RNA polymerases I and II and, for
      some of them, in the bacterial enzyme, thus delineating key elements of the
      active site in eukaryotic RNA polymerases.

PMID- 11454744
TI  - Nikolay Vladimirovich Timofeeff-Ressovsky (1900-1981): twin of the century of
      genetics.

PMID- 11454745
TI  - Development of a genetics education workshop curriculum for Native American
      college and university students.
AB  - The long-term goal of Genetic Education for Native Americans (GENA), a project
      funded by the National Human Genome Research Institute (NHGRI), is to provide a
      balance of scientific and cultural information about genetics and genetic
      research to Native Americans and thereby to improve informed decision making. The
      project provides culturally sensitive education about genetic research to Native
      American medical students and college and university students. Curriculum
      development included focus groups, extensive review of available curricula, and
      collection of information about career opportunities in genetics. Special
      attention was focused on genetic research to identify key concepts, instructional
      methods, and issues that are potentially troublesome or sensitive for Native
      Americans. Content on genetic research and careers in genetics was adapted from a
      wide variety of sources for use in the curriculum. The resulting GENA curriculum
      is based on 24 objectives arranged into modules customized for selected science
      related conference participants. The curriculum was pretested with Native
      American students, medical and general university, health care professionals, and
      basic scientists. Implementation of the curriculum is ongoing. This article
      describes the development and pretesting of the genetics curriculum for the
      project with the expectation that the curriculum will be useful for genetics
      educators working in diverse settings.

PMID- 11454746
TI  - Structure and evolution of the hAT transposon superfamily.
AB  - The maize transposon Activator (Ac) was the first mobile DNA element to be
      discovered. Since then, other elements were found that share similarity to Ac,
      suggesting that it belongs to a transposon superfamily named hAT after hobo from
      Drosophila, Ac from maize, and Tam3 from snapdragon. We addressed the structure
      and evolution of hAT elements by developing new tools for transposon mining and
      searching the public sequence databases for the hallmarks of hAT elements, namely
      the transposase and short terminal inverted repeats (TIRs) flanked by 8-bp host
      duplications. We found 147 hAT-related sequences in plants, animals, and fungi.
      Six conserved blocks could be identified in the transposase of most hAT elements.
      A total of 41 hAT sequences were flanked by TIRs and 8-bp host duplications and,
      out of these, 34 sequences had TIRs similar to the consensus determined in this
      work, suggesting that they are active or recently active transposons.
      Phylogenetic analysis and clustering of hAT sequences suggest that the hAT
      superfamily is very ancient, probably predating the plant-fungi-animal
      separation, and that, unlike previously proposed, there is no evidence that
      horizontal gene transfer was involved in the evolution of hAT elements.

PMID- 11454747
TI  - Saccharomyces cerevisiae rad51 mutants are defective in DNA damage-associated
      sister chromatid exchanges but exhibit increased rates of homology-directed
      translocations.
AB  - Saccharomyces cerevisiae Rad51 is structurally similar to Escherichia coli RecA.
      We investigated the role of S. cerevisiae RAD51 in DNA damage-associated unequal
      sister chromatid exchanges (SCEs), translocations, and inversions. The frequency
      of these rearrangements was measured by monitoring mitotic recombination between
      two his3 fragments, his3-Delta5' and his3-Delta3'::HOcs, when positioned on
      different chromosomes or in tandem and oriented in direct or inverted
      orientation. Recombination was measured after cells were exposed to chemical
      agents and radiation and after HO endonuclease digestion at his3-Delta3'::HOcs.
      Wild-type and rad51 mutant strains showed no difference in the rate of
      spontaneous SCEs; however, the rate of spontaneous inversions was decreased
      threefold in the rad51 mutant. The rad51 null mutant was defective in DNA damage
      associated SCE when cells were exposed to either radiation or chemical DNA
      damaging agents or when HO endonuclease-induced double-strand breaks (DSBs) were
      directly targeted at his3-Delta3'::HOcs. The defect in DNA damage-associated SCEs
      in rad51 mutants correlated with an eightfold higher spontaneous level of
      directed translocations in diploid strains and with a higher level of radiation
      associated translocations. We suggest that S. cerevisiae RAD51 facilitates
      genomic stability by reducing nonreciprocal translocations generated by RAD51
      independent break-induced replication (BIR) mechanisms.

PMID- 11454748
TI  - Suppressors of ssy1 and ptr3 null mutations define novel amino acid sensor
      independent genes in Saccharomyces cerevisiae.
AB  - Ssy1p and Ptr3p are components of the yeast plasma membrane SPS amino acid
      sensor. In response to extracellular amino acids this sensor initiates metabolic
      signals that ultimately regulate the functional expression of several amino acid
      metabolizing enzymes and amino acid permeases (AAPs). As a result of diminished
      leucine uptake capabilities, ssy1Delta leu2 and ptr3Delta leu2 mutant strains are
      unable to grow on synthetic complete medium (SC). Genes affecting the functional
      expression of AAPs were identified by selecting spontaneous suppressing mutations
      in amino acid sensor-independent (ASI) genes that restore growth on SC. The
      suppressors define 11 recessive (asi) complementation groups and 5 dominant (ASI)
      linkage groups. Strains with mutations in genes assigned to these 16 groups fall
      into two phenotypic classes. Mutations in the class I genes (ASI1, ASI2, ASI3,
      TUP1, SSN6, ASI13) derepress the transcription of AAP genes. ASI1, ASI2, and ASI3
      encode novel membrane proteins, and Asi1p and Asi3p are homologous proteins that
      have conserved ubiquitin ligase-like RING domains at their extreme C termini.
      Several of the class II genes (DOA4, UBA1, BRO1, BUL1, RSP5, VPS20, VPS36) encode
      proteins implicated in controlling aspects of post-Golgi endosomal-vacuolar
      protein sorting. The results from genetic and phenotypic analysis indicate that
      SPS sensor-initiated signals function positively to facilitate amino acid uptake
      and that two independent ubiquitin-mediated processes negatively modulate amino
      acid uptake.

PMID- 11454749
TI  - The defect in transcription-coupled repair displayed by a Saccharomyces
      cerevisiae rad26 mutant is dependent on carbon source and is not associated with
      a lack of transcription.
AB  - Nucleotide excision repair (NER) is an evolutionarily conserved pathway that
      removes DNA damage induced by ultraviolet irradiation and various chemical agents
      that cause bulky adducts. Two subpathways within NER remove damage from the
      genome overall or the transcribed strands of transcribing genes (TCR). TCR is a
      faster repair process than overall genomic repair and has been thought to require
      the RAD26 gene in Saccharomyces cerevisiae. Rad26 is a member of the SWI/SNF
      family of proteins that either disrupt chromatin or facilitate interactions
      between the RNA Pol II and transcription activators. SWI/SNF proteins are
      required for the expression or repression of a diverse set of genes, many of
      which are differentially transcribed in response to particular carbon sources.
      The remodeling of chromatin by Rad26 could affect transcription and/or TCR
      following formation of DNA damage and other stress-inducing conditions. We
      speculate that another factor(s) can substitute for Rad26 under particular growth
      conditions. We therefore measured the level of repair and transcription in two
      different carbon sources and found that the defect in the rad26 mutant for TCR
      was dependent on the type of carbon source. Furthermore, TCR did not correlate
      with transcription rate, suggesting that disruption of RAD26 leads to a specific
      defect in DNA repair and not transcription.

PMID- 11454750
TI  - Eukaryotic beta-alanine synthases are functionally related but have a high degree
      of structural diversity.
AB  - beta-Alanine synthase (EC 3.5.1.6), which catalyzes the final step of pyrimidine
      catabolism, has only been characterized in mammals. A Saccharomyces kluyveri pyd3
      mutant that is unable to grow on N-carbamyl-beta-alanine as the sole nitrogen
      source and exhibits diminished beta-alanine synthase activity was used to clone
      analogous genes from different eukaryotes. Putative PYD3 sequences from the yeast
      S. kluyveri, the slime mold Dictyostelium discoideum, and the fruit fly
      Drosophila melanogaster complemented the pyd3 defect. When the S. kluyveri PYD3
      gene was expressed in S. cerevisiae, which has no pyrimidine catabolic pathway,
      it enabled growth on N-carbamyl-beta-alanine as the sole nitrogen source. The D.
      discoideum and D. melanogaster PYD3 gene products are similar to mammalian beta
      alanine synthases. In contrast, the S. kluyveri protein is quite different from
      these and more similar to bacterial N-carbamyl amidohydrolases. All three beta
      alanine synthases are to some degree related to various aspartate
      transcarbamylases, which catalyze the second step of the de novo pyrimidine
      biosynthetic pathway. PYD3 expression in yeast seems to be inducible by
      dihydrouracil and N-carbamyl-beta-alanine, but not by uracil. This work
      establishes S. kluyveri as a model organism for studying pyrimidine degradation
      and beta-alanine production in eukaryotes.

PMID- 11454751
TI  - The budding yeast Msh4 protein functions in chromosome synapsis and the
      regulation of crossover distribution.
AB  - The budding yeast MSH4 gene encodes a MutS homolog produced specifically in
      meiotic cells. Msh4 is not required for meiotic mismatch repair or gene
      conversion, but it is required for wild-type levels of crossing over. Here, we
      show that a msh4 null mutation substantially decreases crossover interference.
      With respect to the defect in interference and the level of crossing over, msh4
      is similar to the zip1 mutant, which lacks a structural component of the
      synaptonemal complex (SC). Furthermore, epistasis tests indicate that msh4 and
      zip1 affect the same subset of meiotic crossovers. In the msh4 mutant, SC
      formation is delayed compared to wild type, and full synapsis is achieved in only
      about half of all nuclei. The simultaneous defects in synapsis and interference
      observed in msh4 (and also zip1 and ndj1/tam1) suggest a role for the SC in
      mediating interference. The Msh4 protein localizes to discrete foci on meiotic
      chromosomes and colocalizes with Zip2, a protein involved in the initiation of
      chromosome synapsis. Both Zip2 and Zip1 are required for the normal localization
      of Msh4 to chromosomes, raising the possibility that the zip1 and zip2 defects in
      crossing over are indirect, resulting from the failure to localize Msh4 properly.

PMID- 11454752
TI  - Characterization of the role of the FluG protein in asexual development of
      Aspergillus nidulans.
AB  - We showed previously that a DeltafluG mutation results in a block in Aspergillus
      nidulans asexual sporulation and that overexpression of fluG activates
      sporulation in liquid-submerged culture, a condition that does not normally
      support sporulation of wild-type strains. Here we demonstrate that the entire N
      terminal region of FluG ( approximately 400 amino acids) can be deleted without
      affecting sporulation, indicating that FluG activity resides in the C-terminal
      half of the protein, which bears significant similarity with GSI-type glutamine
      synthetases. While FluG has no apparent role in glutamine biosynthesis, we
      propose that it has an enzymatic role in sporulation factor production. We also
      describe the isolation of dominant suppressors of DeltafluG(dsg) that should
      identify components acting downstream of FluG and thereby define the function of
      FluG in sporulation. The dsgA1 mutation also suppresses the developmental defects
      resulting from DeltaflbA and dominant activating fadA mutations, which both cause
      constitutive induction of the mycelial proliferation pathway. However, dsgA1 does
      not suppress the negative influence of these mutations on production of the
      aflatoxin precursor, sterigmatocystin, indicating that dsgA1 is specific for
      asexual development. Taken together, our studies define dsgA as a novel component
      of the asexual sporulation pathway.

PMID- 11454753
TI  - Characterization of the EYE2 gene required for eyespot assembly in Chlamydomonas
      reinhardtii.
AB  - The unicellular biflagellate green alga Chlamydomonas reinhardtii can perceive
      light and respond by altering its swimming behavior. The eyespot is a specialized
      structure for sensing light, which is assembled de novo at every cell division
      from components located in two different cellular compartments. Photoreceptors
      and associated signal transduction components are localized in a discrete patch
      of the plasma membrane. This patch is tightly packed against an underlying
      sandwich of chloroplast membranes and carotenoid-filled lipid granules, which
      aids the cell in distinguishing light direction. In a prior screen for mutant
      strains with eyespot defects, the EYE2 locus was defined by the single eye2-1
      allele. The mutant strain has no eyespot by light microscopy and has no organized
      carotenoid granule layers as judged by electron microscopy. Here we demonstrate
      that the eye2-1 mutant is capable of responding to light, although the strain is
      far less sensitive than wild type to low light intensities and orients
      imprecisely. Therefore, pigment granule layer assembly in the chloroplast is not
      required for photoreceptor localization in the plasma membrane. A plasmid
      insertion mutagenesis screen yielded the eye2-2 allele, which allowed the
      isolation and characterization of the EYE2 gene. The EYE2 protein is a member of
      the thioredoxin superfamily. Site-directed mutagenesis of the active site
      cysteines demonstrated that EYE2 function in eyespot assembly is redox
      independent, similar to the auxiliary functions of other thioredoxin family
      members in protein folding and complex assembly.

PMID- 11454754
TI  - Mutants of Chlamydomonas reinhardtii deficient in mitochondrial complex I:
      characterization of two mutations affecting the nd1 coding sequence.
AB  - The mitochondrial rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I)
      comprises more than 30 subunits, the majority of which are encoded by the
      nucleus. In Chlamydomonas reinhardtii, only five components of complex I are
      coded for by mitochondrial genes. Three mutants deprived of complex I activity
      and displaying slow growth in the dark were isolated after mutagenic treatment
      with acriflavine. A genetical analysis demonstrated that two mutations (dum20 and
      dum25) affect the mitochondrial genome whereas the third mutation (dn26) is of
      nuclear origin. Recombinational analyses showed that dum20 and dum25 are closely
      linked on the genetic map of the mitochondrial genome and could affect the nd1
      gene. A sequencing analysis confirmed this conclusion: dum20 is a deletion of one
      T at codon 243 of nd1; dum25 corresponds to a 6-bp deletion that eliminates two
      amino acids located in a very conserved hydrophilic segment of the protein.

PMID- 11454755
TI  - Isolation and characterization of magbane, a magnesium-lethal mutant of
      paramecium.
AB  - Discerning the mechanisms responsible for membrane excitation and ionic control
      in Paramecium has been facilitated by the availability of genetic mutants that
      are defective in these pathways. Such mutants typically are selected on the basis
      of behavioral anomalies or resistance to ions. There have been few attempts to
      isolate ion-sensitive strains, despite the insights that might be gained from
      studies of their phenotypes. Here, we report isolation of "magbane," an ion
      sensitive strain that is susceptible to Mg2+. Whereas the wild type tolerated the
      addition of > or =20 mm MgCl2 to the culture medium before growth was slowed and
      ultimately suppressed (at >40 mm), mgx mutation slowed growth at 10 mm. Genetic
      analysis indicated that the phenotype resulted from a recessive single-gene
      mutation that had not been described previously. We additionally noted that a
      mutant that was well described previously (restless) is also highly sensitive to
      Mg2+. This mutant is characterized by an inability to control membrane potential
      when extracellular K+ concentrations are lowered, due to inappropriate regulation
      of a Ca2+-dependent K+ current. However, comparing the mgx and rst mutant
      phenotypes suggested that two independent mechanisms might be responsible for
      their Mg2+ lethality. The possibility that mgx mutation may adversely affect a
      transporter that is required for maintaining low intracellular Mg2+ is
      considered.

PMID- 11454756
TI  - Multiple signaling mechanisms of the UNC-6/netrin receptors UNC-5 and UNC-40/DCC
      in vivo.
AB  - Cell and growth cone migrations along the dorsoventral axis of Caenorhabditis
      elegans are mediated by the UNC-5 and UNC-40 receptor subtypes for the secreted
      UNC-6 guidance cue. To characterize UNC-6 receptor function in vivo, we have
      examined genetic interactions between unc-5 and unc-40 in the migrations of the
      hermaphrodite distal tip cells. We report that cell migration defects as severe
      as those associated with a null mutation in unc-6 are produced only by null
      mutations in both unc-5 and unc-40, indicating that either receptor retains some
      partial function in the absence of the other. We show that hypomorphic unc-5
      alleles exhibit two distinct types of interallelic genetic interactions. In an
      unc-40 wild-type genetic background, some pairs of hypomorphic unc-5 alleles
      exhibit a partial allelic complementation. In an unc-40 null background, however,
      we observed that unc-5 hypomorphs exhibit dominant negative effects. We propose
      that the UNC-5 and UNC-40 netrin receptors can function to mediate chemorepulsion
      in DTC migrations either independently or together, and the observed genetic
      interactions suggest that this flexibility in modes of signaling results from the
      formation of a variety of oligomeric receptor complexes.

PMID- 11454757
TI  - Tc8, a Tourist-like transposon in Caenorhabditis elegans.
AB  - Members of the Tourist family of miniature inverted-repeat transposable elements
      (MITEs) are very abundant among a wide variety of plants, are frequently found
      associated with normal plant genes, and thus are thought to be important players
      in the organization and evolution of plant genomes. In Arabidopsis, the recent
      discovery of a Tourist member harboring a putative transposase has shed new light
      on the mobility and evolution of MITEs. Here, we analyze a family of Tourist
      transposons endogenous to the genome of the nematode Caenorhabditis elegans
      (Bristol N2). One member of this large family is 7568 bp in length, harbors an
      ORF similar to the putative Tourist transposase from Arabidopsis, and is related
      to the IS5 family of bacterial insertion sequences (IS). Using database searches,
      we found expressed sequence tags (ESTs) similar to the putative Tourist
      transposases in plants, insects, and vertebrates. Taken together, our data
      suggest that Tourist-like and IS5-like transposons form a superfamily of
      potentially active elements ubiquitous to prokaryotic and eukaryotic genomes.

PMID- 11454758
TI  - Complex epistasis and the genetic basis of hybrid sterility in the Drosophila
      pseudoobscura Bogota-USA hybridization.
AB  - We analyzed the genetic basis of postzygotic isolation between the Bogota and USA
      subspecies of Drosophila pseudoobscura. These subspecies diverged very recently
      (perhaps as recently as 155,000 to 230,000 years ago) and are partially
      reproductively isolated: Bogota and USA show very little prezygotic isolation but
      form sterile F1 males in one direction of the hybridization. We dissected the
      basis of this hybrid sterility and reached four main conclusions. First,
      postzygotic isolation appears to involve a modest number of genes: we found large
      chromosome regions that have no effect on hybrid fertility. Second, although
      apparently few in number, the factors causing hybrid sterility show a remarkably
      complex pattern of epistatic interaction. Hybrids suffer no hybrid sterility
      until they carry the "right" allele (Bogota vs. USA) at at least four loci. We
      describe the complete pattern of interactions between all chromosome regions
      known to affect hybrid fertility. Third, hybrid sterility is caused mainly by X
      autosomal incompatibilities. Fourth, hybrid sterility does not involve a maternal
      effect, despite earlier claims to the contrary. In general, our results suggest
      that fewer genes are required for the appearance of hybrid sterility than implied
      by previous studies of older pairs of Drosophila species. Indeed, a maximum
      likelihood analysis suggests that roughly 15 hybrid male steriles separate the
      Bogota and USA subspecies. Only a subset of these would act in F1 hybrids.

PMID- 11454759
TI  - Protein determinants of insertional specificity for the Drosophila gypsy
      retrovirus.
AB  - The gypsy retrovirus invades the germ line of Drosophila females, inserting with
      a high frequency into the ovo locus. Gypsy insertion sites in ovo are clustered
      within a region in the promoter of the ovo gene that contains multiple binding
      sites for the OvoA and OvoB proteins. We found that a 1.3-kb DNA fragment
      containing this region is able to confer gypsy insertional specificity
      independent of its genomic location. The frequency of gypsy insertions into the
      ovo gene is significantly lower in wild-type females than in ovoD1 females. In
      addition, gypsy insertions in ovoD1 females occur during most stages of germ-line
      development whereas insertions in wild-type females occur only in late stages.
      This pattern of temporally specific insertions, as well as the higher frequency
      of insertion in ovoD1 females, correlates with the presence of the OvoA or OvoD1
      proteins. The results suggest that gypsy insertional specificity might be
      determined by the binding of the OvoA repressor isoform to the promoter region of
      the gene.

PMID- 11454760
TI  - Terminal retrotransposons activate a subtelomeric white transgene at the 2L
      telomere in Drosophila.
AB  - Genetically marked P elements inserted into the subtelomeric satellites of
      Drosophila show repression and variegation of the reporter gene. One such white+
      reporter, inserted between the subtelomeric satellite and the terminal HeT-A
      array in the left arm of chromosome 2 (2L), is sensitive to its context; changes
      in the structure of the telomere region can be identified by changes in eye
      color. Addition of HeT-A or TART elements to the 2L terminus increases w+
      expression, and loss of sequence from the end decreases expression. This
      indicates that the telomeric retrotransposons in Drosophila have an activating
      influence on the repressed subterminal reporter gene. Changes in eye color due to
      altered expression of the transgene also allow the detection of interactions
      between homologous telomeres. The 2L arms that terminate in long HeT-A/TART
      arrays showed increased expression of the subterminal w+ transgene when the
      terminal repeats on the homologue are absent or markedly shorter. We propose that
      the chromatin structure of the terminal HeT-A/TART array and the activity of a
      putative promoter/enhancer element on HeT-A are affected by telomeric
      interactions. Such trans-activation may reflect control over HeT-A transcription
      and, thus, transposition activity.

PMID- 11454761
TI  - Identification of a polymorphic mucin-like gene expressed in the midgut of the
      mosquito, Aedes aegypti, using an integrated bulked segregant and differential
      display analysis.
AB  - The identification of putative differentially expressed genes within genome
      regions containing QTL determining susceptibility of the mosquito, Aedes aegypti,
      to the malarial parasite, Plasmodium gallinaceum, was investigated using an
      integrated, targeted approach based on bulked segregant and differential display
      analysis. A mosquito F2 population was obtained from pairwise matings between the
      parasite-susceptible RED strain and the resistant MOYO-R substrain. DNA from
      female carcasses was used to genotype individuals at RFLP markers of known
      chromosomal position around the major QTL (pgs 1). Midguts, dissected 48 hr after
      an infected blood meal, were used to prepare two RNA bulks, each representing one
      of the parental genotypes at the QTL interval. The RNA bulks were compared by
      differential display PCR. A mucin-like protein gene (AeIMUC1) was isolated and
      characterized. The gene maps within the pgs 1 QTL interval and is expressed in
      the adult female midgut. AeIMUC1 RNA abundance decreased with time after blood
      meal ingestion. No differential expression was observed between the two mosquito
      strains but three different alleles with inter- and intrastrain allelic
      polymorphisms including indels and SNPs were characterized. The AeIMUC1 gene
      chromosome location and allelic polymorphisms raise the possibility that the
      protein might be involved in parasite-mosquito interactions.

PMID- 11454762
TI  - Inbreeding changes the shape of the genetic covariance matrix in Drosophila
      melanogaster.
AB  - The pattern of genetic covariation among traits (the G matrix) plays a central
      role in determining the pattern of evolutionary change from both natural
      selection and random genetic drift. Here we measure the effect of genetic drift
      on the shape of the G matrix using a large data set on the inheritance of wing
      characteristics in Drosophila melanogaster. Fifty-two inbred lines with a total
      of 4680 parent-offspring families were generated by one generation of brother
      sister mating and compared to an outbred control population of 1945 families. In
      keeping with the theoretical expectation for a correlated set of additively
      determined traits, the average G matrix of the inbred lines remained proportional
      to the outbred control G matrix with a proportionality constant approximately
      equal to (1 - F), where F is the inbreeding coefficient. Further, the pattern of
      covariance among the means of the inbred lines induced by inbreeding was also
      proportional to the within-line G matrix of the control population with a
      constant very close to the expectation of 2F. Although the average G of the
      inbred lines did not show change in overall structure relative to the outbred
      controls, separate analysis revealed a great deal of variation among inbred lines
      around this expectation, including changes in the sign of genetic correlations.
      Since any given line can be quite different from the outbred control, it is
      likely that in nature unreplicated drift will lead to changes in the G matrix.
      Thus, the shape of G is malleable under genetic drift, and the evolutionary
      response of any particular population is likely to depend on the specifics of its
      evolutionary history.

PMID- 11454763
TI  - DNA variation at the rp49 gene region of Drosophila simulans: evolutionary
      inferences from an unusual haplotype structure.
AB  - An approximately 1.3-kb region including the rp49 gene plus its 5' and 3'
      flanking regions was sequenced in 24 lines of Drosophila simulans (10 from Spain
      and 14 from Mozambique). Fifty-four nucleotide and 8 length polymorphisms were
      detected. All nucleotide polymorphisms were silent: 52 in noncoding regions and 2
      at synonymous sites in the coding region. Estimated silent nucleotide diversity
      was similar in both populations (pi = 0.016, for the total sample). Nucleotide
      variation revealed an unusual haplotype structure showing a subset of 11
      sequences with a single polymorphism. This haplotype was present at intermediate
      frequencies in both the European and the African samples. The presence of such a
      major haplotype in a highly recombining region is incompatible with the neutral
      equilibrium model. This haplotype structure in both a derived and a putatively
      ancestral population can be most parsimoniously explained by positive selection.
      As the rate of recombination in the rp49 region is high, the target of selection
      should be close to or within the region studied.

PMID- 11454764
TI  - Genetic evidence for a protein kinase A/cubitus interruptus complex that
      facilitates processing of cubitus interruptus in Drosophila.
AB  - Hedgehog (Hh) activates a signal transduction pathway regulating Cubitus
      interruptus (Ci). In the absence of Hh, full-length Ci (Ci-155) is bound in a
      complex that includes Costal2 (Cos2) and Fused (Fu). Ci-155 is phosphorylated by
      protein kinase A (PKA), inducing proteolysis to Ci-75, a transcriptional
      repressor. Hh signaling blocks proteolysis and produces an activated Ci-155
      transcriptional activator. The relationship between PKA and the Ci/Cos2/Fu
      complex is unclear. Here we examine Hh target gene expression caused by mutant
      forms of PKA regulatory (PKAr) and catalytic (PKAc) subunits and by the PKAc
      inhibitor PKI(1-31). The mutant PKAr*, defective in binding cAMP, is shown to
      activate Hh target genes solely through its ability to bind and inhibit
      endogenous PKAc. Surprisingly, PKAcA75, a catalytically impaired mutant, also
      activates Hh target genes. To account for this observation, we propose that PKAc
      phosphorylation targeting Ci-155 for proteolysis is regulated within a complex
      that includes PKAc and Ci-155 and excludes PKI(1-31). This complex may permit
      processive phosphorylation of Ci-155 molecules, facilitating their processing to
      Ci-75.

PMID- 11454765
TI  - High-frequency generation of conditional mutations affecting Drosophila
      melanogaster development and life span.
AB  - Genome sequencing reveals that a large percentage of Drosophila genes have
      homologs in humans, including many human disease genes. The goal of this research
      was to develop methods to efficiently test Drosophila genes for functions in
      vivo. An important challenge is the fact that many genes function at more than
      one point during development and during the life cycle. Conditional expression
      systems such as promoters regulated by tetracycline (or its derivative
      doxycycline) are often ideal for testing gene functions. However, generation of
      transgenic animals for each gene of interest is impractical. Placing the
      doxycycline-inducible ("tet-on") promoter directed out of the end of the P
      transposable element produced a mobile, doxycycline-inducible promoter element,
      named PdL. PdL was mobilized to 228 locations in the genome and was found to
      generate conditional (doxycycline-dependent), dominant mutations at high
      frequency. The temporal control of gene overexpression allowed generation of
      mutant phenotypes specific to different stages of the life cycle, including
      metamorphosis and aging. Mutations characterized included inserts in the alpha
      mannosidase II (dGMII), ash1, and pumilio genes. Novel phenotypes were identified
      for each gene, including specific developmental defects and increased or
      decreased life span. The PdL system should facilitate testing of a large fraction
      of Drosophila genes for overexpression and misexpression phenotypes at specific
      developmental and life cycle stages.

PMID- 11454766
TI  - An interaction type of genetic screen reveals a role of the Rab11 gene in oskar
      mRNA localization in the developing Drosophila melanogaster oocyte.
AB  - Abdomen and germ cell development of Drosophila melanogaster embryo requires
      proper localization of oskar mRNA to the posterior pole of the developing oocyte.
      oskar mRNA localization depends on complex cell biological events like cell-cell
      communication, dynamic rearrangement of the microtubule network, and function of
      the actin cytoskeleton of the oocyte. To investigate the cellular mechanisms
      involved, we developed a novel interaction type of genetic screen by which we
      isolated 14 dominant enhancers of a sensitized genetic background composed of
      mutations in oskar and in TropomyosinII, an actin binding protein. Here we
      describe the detailed analysis of two allelic modifiers that identify Drosophila
      Rab11, a gene encoding small monomeric GTPase. We demonstrate that mutation of
      the Rab11 gene, involved in various vesicle transport processes, results in
      ectopic localization of oskar mRNA, whereas localization of gurken and bicoid
      mRNAs and signaling between the oocyte and the somatic follicle cells are
      unaffected. We show that the ectopic oskar mRNA localization in the Rab11 mutants
      is a consequence of an abnormally polarized oocyte microtubule cytoskeleton. Our
      results indicate that the internal membranous structures play an important role
      in the microtubule organization in the Drosophila oocyte and, thus, in oskar RNA
      localization.

PMID- 11454767
TI  - Genetic analysis of the Drosophila Gs(alpha) gene.
AB  - One of the best understood signal transduction pathways activated by receptors
      containing seven transmembrane domains involves activation of heterotrimeric G
      protein complexes containing Gs(alpha), the subsequent stimulation of adenylyl
      cyclase, production of cAMP, activation of protein kinase A (PKA), and the
      phosphorylation of substrates that control a wide variety of cellular responses.
      Here, we report the identification of "loss-of-function" mutations in the
      Drosophila Gs(alpha) gene (dgs). Seven mutants have been identified that are
      either complemented by transgenes representing the wild-type dgs gene or contain
      nucleotide sequence changes resulting in the production of altered Gs(alpha)
      protein. Examination of mutant alleles representing loss-of-Gs(alpha) function
      indicates that the phenotypes generated do not mimic those created by mutational
      elimination of PKA. These results are consistent with the conclusion reached in
      previous studies that activation of PKA, at least in these developmental
      contexts, does not depend on receptor-mediated increases in intracellular cAMP,
      in contrast to the predictions of models developed primarily on the basis of
      studies in cultured cells.

PMID- 11454768
TI  - Genome duplication events and functional reduction of ploidy levels in sturgeon
      (Acipenser, Huso and Scaphirhynchus).
AB  - Sturgeon (order Acipenserformes) provide an ideal taxonomic context for
      examination of genome duplication events. Multiple levels of ploidy exist among
      these fish. In a novel microsatellite approach, data from 962 fish from 20
      sturgeon species were used for analysis of ploidy in sturgeon. Allele numbers in
      a sample of individuals were assessed at six microsatellite loci. Species with
      approximately 120 chromosomes are classified as functional diploid species,
      species with approximately 250 chromosomes as functional tetraploid species, and
      with approximately 500 chromosomes as functional octaploids. A molecular
      phylogeny of the sturgeon was determined on the basis of sequences of the entire
      mitochondrial cytochrome b gene. By mapping the estimated levels of ploidy on
      this proposed phylogeny we demonstrate that (I) polyploidization events
      independently occurred in the acipenseriform radiation; (II) the process of
      functional genome reduction is nearly finished in species with approximately 120
      chromosomes and more active in species with approximately 250 chromosomes and
      approximately 500 chromosomes; and (III) species with approximately 250 and
      approximately 500 chromosomes arose more recently than those with approximately
      120 chromosomes. These results suggest that gene silencing, chromosomal
      rearrangements, and transposition events played an important role in the
      acipenseriform genome formation. Furthermore, this phylogeny is broadly
      consistent with previous hypotheses but reveals a highly supported oceanic
      (Atlantic-Pacific) subdivision within the Acipenser/Huso complex.

PMID- 11454769
TI  - Quantitative trait locus mapping in laboratory mice derived from a replicated
      selection experiment for open-field activity.
AB  - Bidirectional selection in rodents has been used to derive animal models of human
      behavior. An important question is whether selection for behavior operates on a
      limited number of QTL or whether the number and individual contribution of QTL
      varies between selection experiments. To address this question, we mapped QTL in
      two large F2 intercrosses (N = 815 and 821) from the four lines derived from a
      replicated selection experiment for open-field activity, an animal model for
      susceptibility to anxiety. Our analyses indicate that selection operated on the
      same relatively small number of loci in both crosses. Haplotype information and
      the direction of effect of each QTL allele were used to confirm that the QTL
      mapped in the two crosses lie in the same chromosomal regions, although we were
      unable to determine whether QTL in the two crosses represent the same genes. We
      conclude that the genetic architecture of the selected strains is similar and
      relatively simple.

PMID- 11454770
TI  - Positive and negative selection on the human genome.
AB  - The distinction between deleterious, neutral, and adaptive mutations is a
      fundamental problem in the study of molecular evolution. Two significant
      quantities are the fraction of DNA variation in natural populations that is
      deleterious and destined to be eliminated and the fraction of fixed differences
      between species driven by positive Darwinian selection. We estimate these
      quantities using the large number of human genes for which there are polymorphism
      and divergence data. The fraction of amino acid mutations that is neutral is
      estimated to be 0.20 from the ratio of common amino acid (A) to synonymous (S)
      single nucleotide polymorphisms (SNPs) at frequencies of > or =15%. Among the 80%
      of amino acid mutations that are deleterious at least 20% of them are only
      slightly deleterious and often attain frequencies of 1-10%. We estimate that
      these slightly deleterious mutations comprise at least 3% of amino acid SNPs in
      the average individual or at least 300 per diploid genome. This estimate is not
      sensitive to human population history. The A/S ratio of fixed differences is
      greater than that of common SNPs and suggests that a large fraction of protein
      divergence is adaptive and driven by positive Darwinian selection.

PMID- 11454771
TI  - Spectrum of nonrandom associations between microsatellite loci on human
      chromosome 11p15.
AB  - Most evidence about nonrandom association of alleles at different loci, or
      gametic disequilibrium, across extensive anonymous regions of the human genome is
      based on the analysis of overall disequilibrium between pairs of microsatellites.
      However, analysis of interallelic associations is also necessary for a more
      complete description of disequilibrium. Here, we report a study characterizing
      the frequency and strength of both overall and interallelic disequilibrium
      between pairs of 12 microsatellite loci (CA repeats) spanning 19 cM (14 Mb) on
      human chromosome 11p15, in a large sample (810 haplotypes deduced from 405
      individuals) drawn from a single population. Characterization of disequilibrium
      was carried out, taking into account the sign of the observed disequilibria. This
      strategy facilitates detection of associations and gives more accurate estimates
      of their intensities. Our results demonstrate that the incidence of
      disequilibrium over an extensive human chromosomal region is much greater than is
      commonly considered for populations that have expanded in size. In total, 44% of
      the pairs of microsatellite loci and 18% of the pairs of alleles showed
      significant nonrandom association. All the loci were involved in disequilibrium,
      although both the frequency and strength of interallelic disequilibrium were
      distributed nonuniformly along 11p15. These findings are especially relevant
      since significant associations were detected between loci separated by as much as
      17-19 cM (7 cM on average). It was also found that the overall disequilibrium
      masks complicated patterns of association between pairs of alleles, dependent on
      their frequency and size. We suggest that the complex mutational dynamics at
      microsatellite loci could explain the allele-dependent disequilibrium patterns.
      These observations are also relevant to evaluation of the usefulness of
      microsatellite markers for fine-scale localization of disease genes.

PMID- 11454772
TI  - Human DNA sequence variation in a 6.6-kb region containing the melanocortin 1
      receptor promoter.
AB  - An approximately 6.6-kb region located upstream from the melanocortin 1 receptor
      (MC1R) gene and containing its promoter was sequenced in 54 humans (18 Africans,
      18 Asians, and 18 Europeans) and in one chimpanzee, gorilla, and orangutan.
      Seventy-six polymorphic sites were found among the human sequences and the
      average nucleotide diversity (pi) was 0.141%, one of the highest among all
      studies of nuclear sequence variation in humans. Opposite to the pattern observed
      in the MC1R coding region, in the present region pi is highest in Africans
      (0.136%) compared to Asians (0.116%) and Europeans (0.122%). The distributions of
      pi, theta, and Fu and Li's F-statistic are nonuniform along the sequence and
      among continents. The pattern of genetic variation is consistent with a
      population expansion in Africans. We also suggest a possible phase of population
      size reduction in non-Africans and purifying selection acting in the middle
      subregion and parts of the 5' subregion in Africans. We hypothesize diversifying
      selection acting on some sites in the 5' and 3' subregions or in the MC1R coding
      region in Asians and Europeans, though we cannot reject the possibility of
      relaxation of functional constraints in the MC1R gene in Asians and Europeans.
      The mutation rate in the sequenced region is 1.65 x 10(-9) per site per year. The
      age of the most recent common ancestor for this region is similar to that for the
      other long noncoding regions studied to date, providing evidence for ancient gene
      genealogies. Our population screening and phylogenetic footprinting suggest
      potentially important sites for the MC1R promoter function.

PMID- 11454773
TI  - Localization of male-specifically expressed MROS genes of Silene latifolia by PCR
      on flow-sorted sex chromosomes and autosomes.
AB  - The dioecious white campion Silene latifolia (syn. Melandrium album) has
      heteromorphic sex chromosomes, XX in females and XY in males, that are larger
      than the autosomes and enable their separation by flow sorting. The group of MROS
      genes, the first male-specifically expressed genes in dioecious plants, was
      recently identified in S. latifolia. To localize the MROS genes, we used the flow
      sorted X chromosomes and autosomes as a template for PCR with internal primers.
      Our results indicate that the MROS3 gene is located in at least two copies
      tandemly arranged on the X chromosome with additional copy(ies) on the
      autosome(s), while MROS1, MROS2, and MROS4 are exclusively autosomal. The
      specificity of PCR products was checked by digestion with a restriction enzyme or
      reamplification using nested primers. Homology search of databases has shown the
      presence of five MROS3 homologues in A. thaliana, four of them arranged in two
      tandems, each consisting of two copies. We conclude that MROS3 is a low-copy gene
      family, connected with the proper pollen development, which is present not only
      in dioecious but also in other dicot plant species.

PMID- 11454774
TI  - Population dynamics of an Ac-like transposable element in self- and cross
      pollinating arabidopsis.
AB  - Theoretical models predict that the mating system should be an important factor
      driving the dynamics of transposable elements in natural populations due to
      differences in selective pressure on both element and host. We used a PCR-based
      approach to examine the abundance and levels of insertion polymorphism of Ac-III,
      a recently identified Ac-like transposon family, in natural populations of the
      selfing plant Arabidopsis thaliana and its close outcrossing relative,
      Arabidopsis lyrata. Although several insertions appeared to be ancient and shared
      between species, there is strong evidence for recent activity of this element
      family in both species. Sequences of the regions flanking insertions indicate
      that all Ac-III transposons segregating in natural populations are in noncoding
      regions and provide no evidence for local transposition events. Transposon
      display analysis suggests the presence of slightly higher numbers of insertion
      sites per individual but fewer total polymorphic insertions in the self
      pollinating A. thaliana than A. lyrata. Element insertions appear to be
      segregating at significantly lower frequencies in A. lyrata than A. thaliana,
      which is consistent with a reduction in transposition rate, reduction in
      effective population size, or reduced efficacy of natural selection against
      element insertions in selfing populations.

PMID- 11454775
TI  - Multiple losses and transfers to the nucleus of two mitochondrial succinate
      dehydrogenase genes during angiosperm evolution.
AB  - Unlike in animals, the functional transfer of mitochondrial genes to the nucleus
      is an ongoing process in plants. All but one of the previously reported transfers
      in angiosperms involve ribosomal protein genes. Here we report frequent transfer
      of two respiratory genes, sdh3 and sdh4 (encoding subunits 3 and 4 of succinate
      dehydrogenase), and we also show that these genes are present and expressed in
      the mitochondria of diverse angiosperms. Southern hybridization surveys reveal
      that sdh3 and sdh4 have been lost from the mitochondrion about 40 and 19 times,
      respectively, among the 280 angiosperm genera examined. Transferred, functional
      copies of sdh3 and sdh4 were characterized from the nucleus in four and three
      angiosperm families, respectively. The mitochondrial targeting presequences of
      two sdh3 genes are derived from preexisting genes for anciently transferred
      mitochondrial proteins. On the basis of the unique presequences of the nuclear
      genes and the recent mitochondrial gene losses, we infer that each of the seven
      nuclear sdh3 and sdh4 genes was derived from a separate transfer to the nucleus.
      These results strengthen the hypothesis that angiosperms are experiencing a
      recent evolutionary surge of mitochondrial gene transfer to the nucleus and
      reveal that this surge includes certain respiratory genes in addition to
      ribosomal protein genes.

PMID- 11454776
TI  - Quantitative trait loci analysis of powdery mildew disease resistance in the
      Arabidopsis thaliana accession kashmir-1.
AB  - Powdery mildew diseases are economically important diseases, caused by obligate
      biotrophic fungi of the Erysiphales. To understand the complex inheritance of
      resistance to the powdery mildew disease in the model plant Arabidopsis thaliana,
      quantitative trait loci analysis was performed using a set of recombinant inbred
      lines derived from a cross between the resistant accession Kashmir-1 and the
      susceptible accession Columbia glabrous1. We identified and mapped three
      independent powdery mildew quantitative disease resistance loci, which act
      additively to confer disease resistance. The locus with the strongest effect on
      resistance was mapped to a 500-kbp interval on chromosome III.

PMID- 11454777
TI  - Functional divergence in the caspase gene family and altered functional
      constraints: statistical analysis and prediction.
AB  - In this article, we explore the pattern of type I functional divergence (i.e.,
      altered functional constraints or site-specific rate difference) in the caspase
      gene family that is important for apoptosis (programmed cell death) and cytokine
      maturation. By taking advantage of substantial experimental data from caspases,
      the functional/structural basis of our posterior predictions from sequence
      analysis was extensively studied. Our results are as follows: (1) Phylogenetic
      analysis shows that the evolution of major caspase-mediated pathways has been
      facilitated by gene duplications, (2) type I functional divergence (altered
      functional constraints) is statistically significant between two major
      subfamilies, CED-3 and ICE, (3) 4 of 21 predicted amino acid residues (for site
      specific rate difference between CED-3 and ICE) have been verified by
      experimental evidence, and (4) we found that some CED-3 caspases may inherit more
      ancestral functions, whereas other members may employ some recently derived
      functions. Our approach can be cost effective in functional genomics to make
      statistically sound predictions from amino acid sequences.

PMID- 11454778
TI  - Disparity index: a simple statistic to measure and test the homogeneity of
      substitution patterns between molecular sequences.
AB  - A common assumption in comparative sequence analysis is that the sequences have
      evolved with the same pattern of nucleotide substitution (homogeneity of the
      evolutionary process). Violation of this assumption is known to adversely impact
      the accuracy of phylogenetic inference and tests of evolutionary hypotheses. Here
      we propose a disparity index, ID, which measures the observed difference in
      evolutionary patterns for a pair of sequences. On the basis of this index, we
      have developed a Monte Carlo procedure to test the homogeneity of the observed
      patterns. This test does not require a priori knowledge of the pattern of
      substitutions, extent of rate heterogeneity among sites, or the evolutionary
      relationship among sequences. Computer simulations show that the ID-test is more
      powerful than the commonly used chi2-test under a variety of biologically
      realistic models of sequence evolution. An application of this test in an
      analysis of 3789 pairs of orthologous human and mouse protein-coding genes
      reveals that the observed evolutionary patterns in neutral sites are not
      homogeneous in 41% of the genes, apparently due to shifts in G + C content. Thus,
      the proposed test can be used as a diagnostic tool to identify genes and lineages
      that have evolved with substantially different evolutionary processes as
      reflected in the observed patterns of change. Identification of such genes and
      lineages is an important early step in comparative genomics and molecular
      phylogenetic studies to discover evolutionary processes that have shaped
      organismal genomes.

PMID- 11454779
TI  - Accurate partition of individuals into full-sib families from genetic data
      without parental information.
AB  - Two Markov chain Monte Carlo algorithms are proposed that allow the partitioning
      of individuals into full-sib groups using single-locus genetic marker data when
      no parental information is available. These algorithms present a method of moving
      through the sibship configuration space and locating the configuration that
      maximizes an overall score on the basis of pairwise likelihood ratios of being
      full-sib or unrelated or maximizes the full joint likelihood of the proposed
      family structure. Using these methods, up to 757 out of 759 Atlantic salmon were
      correctly classified into 12 full-sib families of unequal size using four
      microsatellite markers. Large-scale simulations were performed to assess the
      sensitivity of the procedures to the number of loci and number of alleles per
      locus, the allelic distribution type, the distribution of families, and the
      independent knowledge of population allelic frequencies. The number of loci and
      the number of alleles per locus had the most impact on accuracy. Very good
      accuracy can be obtained with as few as four loci when they have at least eight
      alleles. Accuracy decreases when using allelic frequencies estimated in small
      target samples with skewed family distributions with the pairwise likelihood
      approach. We present an iterative approach that partly corrects that problem. The
      full likelihood approach is less sensitive to the precision of allelic
      frequencies estimates but did not perform as well with the large data set or when
      little information was available (e.g., four loci with four alleles).

PMID- 11454780
TI  - Statistical issues in the analysis of quantitative traits in combined crosses.
AB  - We consider some practical statistical issues in QTL analysis where several
      crosses originate in multiple inbred parents. Our results show that ignoring
      background polygenic variation in different crosses may lead to biased interval
      mapping estimates of QTL effects or loss of efficiency. Threshold and power
      approximations are derived by extending earlier results based on the Ornstein
      Uhlenbeck diffusion process. The results are useful in the design and analysis of
      genome screen experiments. Several common designs are evaluated in terms of their
      power to detect QTL.

PMID- 11454781
TI  - Estimation of admixture proportions: a likelihood-based approach using Markov
      chain Monte Carlo.
AB  - When populations are separated for long periods and then brought into contact for
      a brief episode in part of their range, this can result in genetic admixture. To
      analyze this type of event we considered a simple model under which two parental
      populations (P1 and P2) mix and create a hybrid population (H). After that event,
      the three populations evolve under pure drift without exchange during T
      generations. We developed a new method, which allows the simultaneous estimation
      of the time since the admixture event (scaled by the population size t(i) =
      T/N(i), where N(i) is the effective population size of population i) and the
      contribution of one of two parental populations (which we call p1). This method
      takes into account drift since the admixture event, variation caused by sampling,
      and uncertainty in the estimation of the ancestral allele frequencies. The method
      is tested on simulated data sets and then applied to a human data set. We find
      that (i) for single-locus data, point estimates are poor indicators of the real
      admixture proportions even when there are many alleles; (ii) biallelic loci
      provide little information about the admixture proportion and the time since
      admixture, even for very small amounts of drift, but can be powerful when many
      loci are used; (iii) the precision of the parameters' estimates increases with
      sample size n = 50 vs. n = 200 but this effect is larger for the t(i)'s than for
      p1; and (iv) the increase in precision provided by multiple loci is quite large,
      even when there is substantial drift (we found, for instance, that it is
      preferable to use five loci than one locus, even when drift is 100 times larger
      for the five loci). Our analysis of a previously studied human data set
      illustrates that the joint estimation of drift and p1 can provide additional
      insights into the data.

PMID- 11454782
TI  - Size of donor chromosome segments around introgressed loci and reduction of
      linkage drag in marker-assisted backcross programs.
AB  - This article investigates the efficiency of marker-assisted selection in reducing
      the length of the donor chromosome segment retained around a locus held
      heterozygous by backcrossing. First, the efficiency of marker-assisted selection
      is evaluated from the length of the donor segment in backcrossed individuals that
      are (double) recombinants for two markers flanking the introgressed gene on each
      side. Analytical expressions for the probability density function, the mean, and
      the variance of this length are given for any number of backcross generations, as
      well as numerical applications. For a given marker distance, the number of
      backcross generations performed has little impact on the reduction of donor
      segment length, except for distant markers. In practical situations, the most
      important parameter is the distance between the introgressed gene and the
      flanking markers, which should be chosen to be as closely linked as possible to
      the introgressed gene. Second, the minimal population sizes required to obtain
      double recombinants for such closely linked markers are computed and optimized in
      the context of a multigeneration backcross program. The results indicate that it
      is generally more profitable to allow for three or more successive backcross
      generations rather than to favor recombinations in early generations.

PMID- 11454785
TI  - Intestinal zonulin: open sesame!

PMID- 11454786
TI  - The father figure in coeliac disease.

PMID- 11454787
TI  - Signals on the immune tract.

PMID- 11454788
TI  - Descartes and the gut: "I'm pink therefore I am".

PMID- 11454789
TI  - Serum antibody responses to Clostridium difficile toxin A: predictive and
      protective?

PMID- 11454790
TI  - Coeliac disease in the father affects the newborn.
AB  - BACKGROUND AND AIMS: Untreated coeliac disease in the mother is associated with
      lower birth weight. We examined the risk of adverse neonatal outcome when the
      infant's mother, father, or other relative suffered from known coeliac disease.
      METHODS: Mothers answered a questionnaire a few days after the birth of their
      infant. Of a total of 10,597 single birth infants from Southeast Sweden, 53
      infants had a mother with coeliac disease (father 27, sibling 70, other close
      relative 442). Adjusted odds ratios and adjusted differences for neonatal outcome
      were calculated. RESULTS: Infants whose father suffered from coeliac disease had
      a lower birth weight (95% adjusted confidence interval (CI) -459, -72 g), more
      often belonged to the low birth weight (LBW) category (LBW < or =2499 g) (95% CI
      adjusted odds ratio (AOR) 1.48--17.18), and had a shorter pregnancy duration (95%
      adjusted CI -1.53, -0.08 weeks) than non-coeliac controls. They also weighed less
      than infants whose father suffered from other autoimmune diseases (95% CI -549, 
      93 g). Infants whose mother suffered from coeliac disease had a lower birth
      weight (95% adjusted CI -370, -74 g) and more often belonged to the LBW category
      (95% CI AOR 2.60--15.08) than non-coeliac controls. These infants were more often
      in the LBW category than infants whose mother suffered from non-diabetic
      autoimmune diseases (95% CI AOR 1.24--9.65). Coeliac disease in other relatives
      was not associated with any adverse effect on neonatal outcome. CONCLUSIONS: This
      study suggests that even treated coeliac disease, in either of the parents, has a
      negative effect on pregnancy, resulting in lower birth weight and perhaps shorter
      duration of pregnancy.

PMID- 11454791
TI  - Keratinocyte growth factor and coeliac disease.
AB  - BACKGROUND: Coeliac disease is characterised by increased epithelial renewal
      associated with a mucosal T cell response to gliadin. Keratinocyte growth factor
      (KGF) is produced by cytokine activated gut stromal cells and may be a link
      between mucosal T cell activation in untreated coeliac disease and epithelial
      hyperplasia. AIMS: To characterise expression of KGF in coeliac disease. METHODS:
      KGF transcripts in coeliac disease were measured by quantitative competitive
      reverse transcription-polymerase chain reaction (RT-PCR) and localised using in
      situ hybridisation. KGF production by gluten reactive CD4+ T cell clones was
      examined. In addition, KGF transcripts were measured following ex vivo challenge
      of coeliac biopsies with a peptic-tryptic digest of gliadin. RESULTS: KGF
      transcripts were elevated in coeliac biopsies compared with normal controls but
      were not different from non-coeliac disease controls. By in situ hybridisation,
      KGF mRNA containing cells were present in the upper half of the lamina propria,
      most abundantly just under the epithelium. There was no signal from cells within
      the epithelium. Gluten reactive T cell clones did not make KGF. In vitro
      challenge of coeliac biopsies generated a strong interferon gamma response but a
      specific KGF response could not be detected because of an extremely high number
      of KGF transcripts in all cultured biopsies. CONCLUSIONS: KGF is overexpressed in
      coeliac biopsies and in tissues with non-coeliac enteropathy. No evidence was
      found for KGF production by intraepithelial lymphocytes or lamina propria T
      cells.

PMID- 11454792
TI  - Erythropoietin acts as a trophic factor in neonatal rat intestine.
AB  - BACKGROUND: Erythropoietin (Epo) receptors are present on enterocytes of fetal
      and neonatal small bowel but the role of Epo in the bowel is not known. AIMS: We
      tested the following hypotheses: (1) enterally dosed Epo is absorbed from the
      intestines of neonatal rats, (2) Epo acts as a trophic factor in developing small
      bowel, and (3) the trophic effects of Epo are dependent on the route of
      administration. METHODS: The dose dependent effects of enterally dosed
      recombinant human erythropoietin (rEpo 0--1000 U/kg/day) were studied in
      artificially raised rat pups and compared with dam raised controls and dam raised
      pups given rEpo in rat milk. After one week, reticulocyte counts, haematocrits,
      and plasma Epo concentrations were measured, and calibrated morphometric
      measurements of villi were performed. The effects of route of rEpo administration
      (enteral v parenteral) on erythropoiesis, bowel growth, and disaccharidase
      activity were studied in nursing pups treated for one and two weeks. RESULTS:
      Serum Epo concentrations ranged from undetectable (<0.6 mU/ml) to 8.4 mU/ml in
      control and enterally dosed pups (median 1.8 mU/ml), and from 4.9 to 82.3 mU/ml
      (median 20.4 mU/ml) in parenterally dosed animals. No increase in haematocrit or
      reticulocyte count was noted in enterally treated pups compared with controls
      after up to two weeks of treatment. Small bowel length was greater in rEpo
      treated pups, and a dose dependent increase in villus surface area which was
      independent of the route of dosing and associated with increased BrdU uptake was
      found. CONCLUSIONS: rEpo is not enterally absorbed in an intact and functional
      form from the intestines of neonatal rat pups. Thus enterally dosed rEpo has no
      erythropoietic effects. However, rEpo acts as a trophic factor in developing rat
      small bowel whether given enterally or parenterally.

PMID- 11454793
TI  - Loss of transforming growth factor beta signalling in the intestine contributes
      to tissue injury in inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the
      gastrointestinal tract caused by an abnormal and uncontrolled immune response to
      one or more normally occurring gut constituents. AIM: Given the effects of
      transforming growth factor beta1 (TGF-beta1) on both the immune system and
      extracellular matrix, we postulated that alterations in TGF-beta signalling in
      intestinal epithelial cells may play an important role in the development of IBD.
      METHODS: TGF-beta signalling was inactivated in mouse intestine by expressing a
      dominant negative mutant form of the TGF-beta type II receptor under the control
      of the mouse intestinal trefoil peptide (ITF)/TFF3 promoter. Transgenic mice (ITF
      dnRII) developed spontaneous colitis presenting with diarrhoea, haematochezia,
      and anal prolapse when not maintained under specific pathogen free (SPF)
      conditions. Under SPF conditions we induced colitis by mixing dextran sodium
      sulphate (DSS) in drinking water to examine the significance of loss of TGF-beta
      signalling in the pathogenesis of IBD. RESULTS: Transgenic mice showed increased
      susceptibility to DSS induced IBD, and elicited increased expression of major
      histocompatibility complex class II, generation of autoantibodies against
      intestinal goblet cells, and increased activity of matrix metalloproteinase in
      intestinal epithelial cells compared with wild-type littermates challenged with
      DSS. CONCLUSIONS: Deficiency of TGF-beta signalling specifically in the intestine
      contributes to the development of IBD. Maintenance of TGF-beta signalling may be
      important in regulating immune homeostasis in the intestine

PMID- 11454794
TI  - Inflammatory bowel disease and laterality: is left handedness a risk?
AB  - BACKGROUND: Left handedness has been associated with inflammatory bowel disease
      (IBD) and autoimmune diseases. AIMS: To determine whether left handedness is
      associated with IBD in two prospective national birth cohorts. METHODS: Subjects
      with Crohn's disease (CD) and ulcerative colitis (UC) were identified from two
      national longitudinal birth cohorts at age 26 years (1970 British Cohort Study
      (BCS70), born in 1970) and age 33 years (National Child Development Study (NCDS),
      born in 1958). Laterality was determined at age 10 (BCS70) or seven (NCDS) years,
      based on hand preference for writing and foot preference for kicking a ball
      (BCS70 only). Multiple logistic regression was used to assess the relationship of
      handedness with CD, UC, and IBD in the cohorts combined and adjusted for sex.
      RESULTS: Both cohorts combined showed increased adjusted relative odds of 2.13
      (95% confidence interval (CI) 0.97--4.65; p=0.059), 2.13 (95% CI 0.92--4.91; p=0.
      077), and 2.13 (95% CI 1.20--3.78; p=0.010) for CD, UC, and IBD, respectively in
      left handers. CONCLUSIONS: The study suggests a link between IBD and left
      handedness which may be genetic and/or environmental in origin.

PMID- 11454795
TI  - Perception of changes in wall tension of the proximal stomach in humans.
AB  - BACKGROUND: Hypersensitivity to distension of the stomach is a frequent finding
      in functional dyspepsia. During gastric distension studies both wall tension and
      elongation are increased. AIM: We wished to distinguish changes in wall tension
      from changes in elongation in the genesis of perception of mechanical stimuli
      originating from the proximal stomach in healthy subjects. SUBJECTS AND METHODS:
      Twenty six volunteers were studied using gastric barostat and antroduodenal
      manometry. In 14 subjects, stepwise isobaric and isovolumetric distensions were
      performed before and during erythromycin infusion. In all volunteers, on a
      separate occasion, phasic contractions of the proximal stomach were detected as
      intraballoon pressure increases during fixed volume inflation. These contractions
      were matched with perception changes during two 10 minute periods, before and
      during administration of erythromycin. RESULTS: Erythromycin significantly
      lowered the perception and discomfort thresholds during stepwise gastric
      distension. During fixed volume inflation, erythromycin increased the number and
      amplitude of fundic contractions and enhanced their perception from 51.1 (7.4)%
      to 64.0 (4.7)%. The proportion of perception score increases coinciding with
      fundic contractions increased from 47.3 (0.7)% to 81.5 (0.5)%. The amplitude of
      correctly identified isolated fundic pressure waves was higher compared with non
      identified waves. CONCLUSIONS: These results support the hypothesis that changes
      in gastric wall tension may be involved in the genesis of symptoms originating
      from the stomach.

PMID- 11454796
TI  - Relationship between psychological state and level of activity of extrinsic gut
      innervation in patients with a functional gut disorder.
AB  - BACKGROUND: Anxiety and depression are known to be associated with alterations in
      central autonomic activity, and this may manifest as a functional gut
      disturbance. However, the final expression of motility disturbance is non
      specific and non-quantifiable. This study examines the relationship between
      psychological state and psychosocial functioning with a new direct measure of the
      level of activity of extrinsic autonomic gut innervation, rectal mucosal Doppler
      blood flow. MATERIALS AND METHODS: Thirty four female patients (mean age 36
      years, range 19--45) with constipation for greater than five years and 19 healthy
      women (mean age 38 years, range 21--60) were studied. They completed the general
      health questionnaire-28 point scale (GHQ-28; psychosocial functioning) and the
      Bem sex role inventory (BSRI; an index of women's psychological feelings about
      their own femininity). On the same day they underwent measurement of rectal
      mucosal Doppler blood flow, a new validated measure of the activity of gut
      extrinsic nerve innervation. Measurements were made during the follicular phase
      and in the fasted state. RESULTS: Women with constipation scored higher on the
      total GHQ-28 score and the somatisation (p=0.05) and anxiety (p=0.05) subscales
      of the GHQ-28. There was a negative correlation between mucosal blood flow and
      GHQ somatisation subscale (r=-0.45, p<0.005), anxiety (r=-0.38, p<0.05), and
      depression (r=-0.40, p<0.01) scores in women with constipation. Although
      constipated women scored no higher than controls on the BSRI, there was a
      significant negative correlation between blood flow and BSRI score (r=-0.49,
      p<0.005) for constipated women. CONCLUSIONS: General psychosocial function,
      somatisation, anxiety, depression, and feelings about female role are impaired in
      women with constipation and associated with altered rectal mucosal blood flow, a
      measure of extrinsic gut innervation. These findings suggest that psychological
      factors are likely to influence gut function via autonomic efferent neural
      pathways.

PMID- 11454797
TI  - Response to a behavioural treatment, biofeedback, in constipated patients is
      associated with improved gut transit and autonomic innervation.
AB  - BACKGROUND: Although behavioural treatment (biofeedback) successfully treats the
      pelvic floor abnormalities in patients with idiopathic constipation, many
      patients also normalise their impaired bowel frequency. We postulated that a
      response may be associated with altered cerebral outflow via extrinsic autonomic
      nerves to the gut. We investigated whether treatment changes extrinsic
      innervation, using mucosal laser Doppler flowmetry, whether autonomic changes are
      gut specific, and whether it changes gut transit. MATERIALS AND METHODS: Forty
      nine patients (44 female, mean age 39 years) with idiopathic constipation were
      studied before and after biofeedback treatment (mean five sessions). Rectal
      mucosal blood flow was measured by laser Doppler flowmetry to assess direct
      extrinsic gut nerve autonomic activity. To assess general autonomic activity, RR
      (interval between successive R waves on the electrocardiogram) variability,
      Valsalva ratio, orthostatic adjustment ratio, and phase II:IV blood pressure
      ratio (II:IV) of the Valsalva manoeuvre were measured. All autonomic tests were
      compared with those of 26 healthy volunteers (19 female, mean age 37 years).
      RESULTS: Twenty nine of 49 patients were symptomatically improved. Treatment
      reduced those with < or =3 bowel actions per week (27 v 9, pre v post), need to
      strain (26 v 9), and laxative or suppository use (34 v 9). Biofeedback reduced
      retained markers by 32% in those with slow transit and by 20% in those with
      normal transit. Twenty two had slow transit before treatment-14 felt symptomatic
      improvement of whom 13 developed normal transit. There was a significantly
      greater increase in rectal mucosal blood flow in patients who subjectively
      improved compared with those who did not (29% v 7%; p<0.03) and in those with
      improved bowel frequency (33% v 9%, increased v unchanged bowel frequency;
      p<0.05). Thirty five patients had abnormal RR variability and 33 an abnormal
      Valsalva ratio; one had an abnormal orthostatic adjustment ratio and one an
      abnormal II:IV ratio. None of the general cardiorespiratory autonomic reflexes
      was changed by treatment. CONCLUSIONS: Biofeedback treatment affects more than
      the pelvic floor. Successful outcome after biofeedback treatment is associated
      with improved activity of the direct cerebral innervation to the gut and improved
      gut transit. This effect is gut specific; cardiovascular autonomic reflexes were
      not altered.

PMID- 11454798
TI  - SOX10 is abnormally expressed in aganglionic bowel of Hirschsprung's disease
      infants.
AB  - BACKGROUND: The primary pathology of Hirschsprung's disease (HD) is a congenital
      absence of ganglion cells in the caudal most gut. The spastic aganglionic bowel
      is often innervated by a network of hypertrophied nerve fibres. Recently,
      mutations of SOX10 have been identified in patients with HD but only in those
      with Waardenburg-Shah syndrome. AIMS: To understand the molecular basis for the
      pathogenesis of HD we intended to determine the specific cell lineages in the
      enteric nervous system which normally express SOX10 but are affected in disease
      conditions. METHODS: We studied colon biopsies from 10 non-syndromic HD patients,
      aged three months to four years, and 10 age matched patients without HD as normal
      controls. The absence of mutation in the SOX10 gene of HD patients was confirmed
      by DNA sequencing. Expression and cellular distribution of SOX10 in bowel
      segments of normal and HD infants were examined by reverse transcription
      polymerase chain reaction and in situ hybridisation. RESULTS: We found that in
      normal infants and normoganglionic bowel segments of HD patients, SOX10 was
      expressed in both neurones and glia of the enteric plexuses and in the nerves
      among the musculature in normal colon. In the aganglionic bowel segments of
      patients, SOX10 expression was consistently lower and was found to be associated
      with the hypertrophic nerve trunks in the muscle and extrinsic nerves in the
      serosa. CONCLUSION: We conclude that SOX10 is normally required postnatally in
      the functional maintenance of the entire enteric nervous system, including
      neurones and glia. In non-syndromic HD patients who do not have the SOX10
      mutation, the SOX10 gene expressed in the sacral region may be involved in the
      pathogenesis of the abnormal nerve trunks through interaction with other factors.

PMID- 11454799
TI  - The prognostic value of quality of life scores during treatment for oesophageal
      cancer.
AB  - BACKGROUND: Quality of life (QL) data are useful to evaluate the effectiveness of
      treatment. Accumulating evidence suggests that QL data may predict survival.
      AIMS: In this study we investigated if baseline QL scores and changes in QL
      scores before and after intervention are prognostic for patients with oesophageal
      cancer. PATIENTS: Between 1993 and 1995, 92 consecutive new patients with
      oesophageal cancer were studied; 89 were followed until death or the end of the
      study period (survival of seven patients was censored in May 1999). METHODS: All
      patients completed the European Organisation for Research and Treatment of Cancer
      (EORTC) core questionnaire (EORTC QLQ-C30) and the dysphagia scale of the
      oesophageal module (EORTC QLQ-OES24) before treatment and at regular intervals
      throughout the study. Cox's proportional hazards models assessed the impact of
      baseline QL variables and changes in QL scores on survival. RESULTS: Cox's
      proportional hazards models, adjusting for associations between QL scores, age,
      and TNM stage, found that physical function at baseline was significantly
      associated with survival (p=0.002). An increase in physical function score of 10
      points corresponded to a 12% reduction in the likelihood of death at any given
      time (95% confidence intervals 4--18%). Further exploratory multivariable
      analyses suggested that improvement in emotional function six months after
      treatment was significantly related to longer survival (p<0.0001). CONCLUSIONS:
      These data provide evidence to support a relationship between patient rated
      scores of QL and survival. Further understanding of the associations between QL
      and clinical variables is needed.

PMID- 11454800
TI  - Decision analysis in the surgical treatment of patients with familial adenomatous
      polyposis: a Dutch-Scandinavian collaborative study including 659 patients.
AB  - BACKGROUND AND AIMS: The choice of colorectal surgery in patients with familial
      adenomatous polyposis lies between the morbidity of proctocolectomy and ileum
      pouch-anal anastomosis (IPAA) and the mortality from rectal cancer after total
      colectomy and ileorectal anastomosis (IRA). The aims of the present study were:
      (1) to assess the risk of dying from rectal cancer after IRA, (2) to compare the
      life expectancy between patients with an IRA and those with an IPAA, and (3) to
      investigate whether regular endoscopic examination of the rectum leads to
      detection of cancer at an earlier stage. METHODS: Clinical and pathological data
      on 659 patients who underwent colectomy and ileorectal anastomosis were collected
      from four national polyposis registries-that is, in Denmark, Finland, Sweden, and
      the Netherlands. Data were analysed using survival analysis methods. Decision
      analysis was used to compare the life expectancy between patients with an IRA and
      those with an IPAA. RESULTS: A total of 47 patients developed rectal cancer after
      IRA. The risk of dying from rectal cancer was 12.5% (95% confidence interval 7.1-
      17.9%) by age 65. Compared with IRA, IPAA would lead to an increase in life
      expectancy of 1.8 years. Seventy five per cent of patients with rectal cancer had
      a negative rectoscopy within 12 months before the diagnosis. CONCLUSION: IRA is
      associated with substantial mortality due to rectal cancer. Follow up
      examinations of the rectum does not have sufficient preventive effect on
      morbidity and mortality of rectal cancer.

PMID- 11454801
TI  - Overexpression of the CD155 gene in human colorectal carcinoma.
AB  - BACKGROUND AND AIMS: The Tage4 gene (tumour associated glycoprotein E4) is
      overexpressed in rat colon tumours and Min mouse intestinal adenomas. The rat
      Tage4 protein has approximately 40% identity with human CD155, a member of the
      immunoglobulin superfamily coding for a transmembrane protein capable of serving
      as an entry receptor for poliovirus, porcine pseudorabies virus, and bovine
      herpesvirus 1. Analysis of the rat Tage4 gene has revealed structural and
      functional similarities with the human CD155 gene. We therefore investigated
      expression of the CD155 gene in human colorectal carcinomas. METHODS: Overall
      CD155 expression was assessed by semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemical analysis using tissue
      specimens from patients with colorectal adenomas and adenocarcinomas. We also
      used a qualitative RT-PCR assay to determine relative expression of different
      splicing variants in each sample. RESULTS: mRNA levels of CD155 were increased in
      six of six colorectal cancer tissues compared with the tumour free colon mucosa.
      Immunohistochemical analysis revealed an increased level of CD155 protein in 12
      of 12 samples. The qualitative RT-PCR assay revealed that relative expression of
      the different CD155 variant transcripts was similar in the different normal and
      cancer samples tested, indicating that this overexpression is not associated with
      a particular mRNA variant generated by alternative splicing of the CD155 gene.
      CONCLUSION: We have shown for the first time that the CD155 gene is overexpressed
      in colorectal carcinoma and that this overexpression begins at an early stage in
      tumorigenesis and continues to late stages.

PMID- 11454802
TI  - Arginine induced acute pancreatitis alters the actin cytoskeleton and increases
      heat shock protein expression in rat pancreatic acinar cells.
AB  - Arginine induced acute pancreatitis was evaluated as a novel and distinct form of
      experimental pancreatitis with particular attention to the actin cytoskeleton and
      expression of heat shock or stress proteins. Arginine induced a dose related
      necrotising pancreatitis in rats, as shown by histological evaluation, and an
      increase in serum amylase. Severe pancreatitis induced by 4.5 g/kg arginine was
      accompanied by dramatic changes in the actin cytoskeleton, as visualised with
      rhodamine phallodin. Intermediate filaments were also disrupted, as visualised by
      cytokeratin 8/18 immunocytochemistry. Arginine pancreatitis was accompanied by a
      stress response with a large increase in the small heat shock protein HSP27, as
      well as HSP70, peaking at 24 hours and localised to acinar cells. There was a
      lower increase in HSP60 and HSP90 and no effect on GRP78. HSP27 was also shifted
      to phosphorylated forms during pancreatitis. A lower dose of arginine (3.0 g/kg)
      induced less pancreatitis but a larger increase in HSP70 and HSP27 expression and
      phosphorylation of HSP27. Thus HSP expression can be overwhelmed by severe
      damage. The present work in conjunction with earlier work on caerulein induced
      pancreatitis indicates that changes in the actin cytoskeleton are an early
      component in experimental pancreatitis.

PMID- 11454803
TI  - Interferon gamma inhibits growth of human pancreatic carcinoma cells via caspase
      1 dependent induction of apoptosis.
AB  - BACKGROUND AND AIMS: The poor prognosis of pancreatic cancer is partly due to
      resistance to a broad spectrum of apoptotic stimuli. To identify intact
      proapoptotic pathways of potential clinical relevance, we characterised the
      effects of interferon gamma (IFN-gamma) on growth and survival in human
      pancreatic cancer cells. METHODS: IFN-gamma receptor expression and signal
      transduction were examined by reverse transcriptase-polymerase chain reaction (RT
      PCR), immunoprecipitation, western blot analysis, and transactivation assays.
      Effects on cell growth and survival were evaluated in terms of cell numbers,
      colony formation, cell cycle analysis, DNA fragmentation, and poly(ADP ribose)
      polymerase (PARP) cleavage. RESULTS: All four pancreatic cancer cell lines
      examined expressed functional IFN-gamma receptors and downstream effectors,
      including the putative tumour suppressor interferon regulatory factor 1 (IRF-1).
      IFN-gamma treatment profoundly inhibited anchorage dependent and independent
      growth of pancreatic cancer cells. Cell cycle analyses revealed subdiploid cells
      suggesting apoptosis, which was confirmed by demonstration of DNA fragmentation
      and PARP cleavage. Time and dose dependency of apoptosis induction and growth
      inhibition correlated closely, identifying apoptosis as the main, if not
      exclusive, mechanism responsible for growth inhibition. Apoptosis was preceded by
      upregulation of procaspase-1 and accompanied by proteolytic activation.
      Furthermore, the caspase inhibitor z-vad-fmk completely prevented IFN-gamma
      mediated apoptosis. CONCLUSIONS: These results identify an intact proapoptotic
      pathway in pancreatic cancer cells and suggest that IRF-1 and/or procaspase-1 may
      represent potential therapeutic targets to be further explored.

PMID- 11454804
TI  - Interferon responsiveness in patients infected with hepatitis C virus 1b differs
      depending on viral subtype.
AB  - BACKGROUND: Genotype 1b of hepatitis C virus (HCV) comprises mainly three
      subtypes, each named for its geographic prevalence (worldwide, W; Japan, J; and
      not in Japan, NJ). AIM: To characterise the newly identified subtypes of genotype
      1b and to review factors associated with response to interferon (IFN) for each
      subtype. PATIENTS: Chronic hepatitis patients (80 men and 41 women; mean age 48.5
      years, range 20.7--69.3) with HCV genotype 1b (W type, n=41; J type, n=38) or
      genotype 2a (n=42) were treated according to the same IFN protocol. Forty four
      patients (36.4%) negative for serum HCV RNA six months after cessation of
      treatment were considered complete responders. METHODS: Factors associated with
      complete response were investigated. RESULTS: Genotype 2a patients had lower
      viral loads (odds ratio 0.11 (95% confidence intervals (CI) 0.049--0.256)) and a
      better IFN response (odds ratio 0.25 (95% CI 0.117--0.552)) than genotype 1b
      patients whereas W type and J type patients had similar viral loads and responses
      to IFN. IFN response in W type patients was associated with female sex (odds
      ratio 0.23 (95% CI 0.055--0.983)) and low viral load (odds ratio 84.00 (95% CI
      14.04--502.6)) whereas response in J type patients was related to transfusion
      history (odds ratio 7.20 (95% CI 1.443--35.91)), low viral load (odds ratio 117.0
      (95% CI 17.82--768.3)), and genetic mutation in the interferon sensitivity
      determining region of the virus (odds ratio 0.08 (95% CI 0.013--0.553)).
      Multivariate analysis found low viral load (odds ratio 64.19 (95% CI 14.66-
      281.06)) to be the only significant independent factor associated with IFN
      response. CONCLUSIONS: Factors associated with IFN responsiveness in HCV
      infection differ with viral subtype.

PMID- 11454805
TI  - The cardiac response to exercise in cirrhosis.
AB  - BACKGROUND: Impaired exercise capacity and oxygen consumption are common in
      cirrhosis. AIM: To explore the relationship between possible myocardial
      dysfunction and exercise tolerance in cirrhosis. METHODS: Cardiac responses to
      exercise, using radionuclide angiography and graded upright cycle ergometry with
      oxygen consumption, were assessed before and after exercise in 39 cirrhotics
      patients and compared with 12 age and sex matched healthy volunteers. Baseline
      cardiac chamber dimensions and wall thickness, ejection fraction, and diastolic
      function were measured using two dimensional echocardiography is all subjects.
      RESULTS: Baseline diastolic dysfunction with prolonged isovolumic relaxation
      times (p=0.02), left atrial enlargement, and left ventricular wall thickening
      were present in all cirrhotics (p=0.02), despite increased mean ejection
      fraction. With graded exercise, cirrhotics achieved 71 (4)% (p=0.03) (pre
      ascitics) and 46 (3)% (p<0.001) (ascitics) of predicted work loads, respectively,
      without significant increases in ejection fraction. The smaller absolute and
      percentage increases in cardiac output (p=0.003) in the cirrhotics were
      associated with significantly reduced oxygen consumption (p=0.003) and anaerobic
      threshold (p<0.001), and correlated significantly with work and metabolic
      parameters. CONCLUSIONS: Impaired exercise capacity in cirrhosis is associated
      with myocardial thickening and ventricular stiffness leading to decreased
      diastolic function, inotropic and chronotropic incompetence under conditions of
      stress, with metabolic consequences. This picture is compatible with the
      condition now known as cirrhotic cardiomyopathy.

PMID- 11454806
TI  - Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic
      variant.
AB  - The clinical and pathological findings of four females with primary biliary
      cirrhosis (PBC) with an unusual and hitherto not well recognised course are
      reported. Patients suffered severe pruritus and weight loss with progressive
      icteric cholestasis which did not respond to such treatments as ursodeoxycholic
      acid and immunosuppressives. In all cases liver histology revealed marked bile
      duct loss without however significant fibrosis or cirrhosis. Further diagnostic
      studies and repeat biopsies confirmed the absence of liver cirrhosis as well as
      other potential causes of hyperbilirubinaemia. Comparison of the fibrosis
      ductopenia relationship for our cases with that for a group of 101 non-cirrhotic
      PBC patients indicated that in the former the severity of bile duct loss relative
      to the amount of fibrosis was significantly higher. The proportion of portal
      triads containing an interlobular bile duct was 3%, 4%, 6%, and 10% compared with
      45% (median; range 8.3--100%) for controls (p<0.001). Three patients received a
      liver transplant 6--7 years after the first manifestation of PBC because of
      progressive cholestasis, refractory pruritus, and weight loss, while the fourth
      patient is considering this option. In one case cirrhosis had developed at the
      time of transplantation while the others still had non-cirrhotic disease. These
      cases suggest that cholestatic jaundice in non-cirrhotic PBC may be secondary to
      extensive "premature" or accelerated intrahepatic bile duct loss. Although the
      extent of fibrosis may be limited initially, progression to cirrhosis appears to
      be inevitable in the long run. Despite intact protein synthesis and absence of
      cirrhotic complications, liver transplantation in the pre-cirrhotic stage for
      preventing malnutrition and to improve quality of life should be considered for
      these patients.

PMID- 11454807
TI  - Osteoporosis in primary biliary cirrhosis revisited.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is increasingly being diagnosed in
      the earlier non-cholestatic stages of disease. Accepted wisdom has been that PBC
      is frequently complicated by osteoporosis. Whether this association holds true
      for the broader spectrum of PBC patients now recognised has not as yet been
      studied. AIMS: To examine the extent to which osteoporosis occurs more commonly
      in PBC patients than in normal individuals of the same age and sex. DESIGN:
      Retrospective review of a large cohort of well characterised PBC patients.
      PATIENTS: A total of 272 PBC patients with definite or probable PBC followed up
      for a mean of 10.1 years (total follow up 2726 patient years) who had at least
      one bone mineral density measurement (BMD). RESULTS: In this unselected group of
      PBC patients, mean Z scores (number of SDs from age and sex matched normal mean
      values) at the neck of femur (NOF) and lumbar spine (LS) at first BMD measurement
      (7 (6) years after PBC diagnosis) were -0.1 (1.4) and 0.1 (1.4), respectively. At
      first BMD measurement, 18 PBC patients had Z scores less than -2.0 and 85 had T
      scores less than -2.5. No factors predictive of osteoporosis were found in
      affected patients. A total of 957 BMD measurements were performed (0.35 per
      patient year of follow up); 220 patients had two or more measurements. No patient
      went on to develop de novo osteoporosis during follow up. In the 51 patients (who
      were clinically representative of the whole group) who received no PBC or bone
      related treatment during follow up, %BMD changes per year at the NOF and LS were 
      1.6 (3.2) and 0.1 (2.2), respectively. No variance in this "natural" rate of BMD
      measurement was seen in patients receiving PBC modulating agents (including
      prednisolone and UDCA) or osteoporosis prophylaxis/therapy. Significant
      improvement at the LS was seen in patients undergoing liver transplantation.
      CONCLUSIONS: Osteoporosis is not a specific complication of PBC.

PMID- 11454808
TI  - Association of the tumour necrosis factor alpha -308 but not the interleukin 10 
      627 promoter polymorphism with genetic susceptibility to primary sclerosing
      cholangitis.
AB  - BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a chronic
      cholestatic liver disease of unknown aetiology. Abnormalities in immune
      regulation and genetic associations suggest that PSC is an immune mediated
      disease. Several polymorphisms within the tumour necrosis factor alpha (TNF
      alpha) and interleukin 10 (IL-10) promoter genes have been described which
      influence expression of these cytokines. This study examines the possible
      association between polymorphisms at the -308 and -627 positions in the TNF-alpha
      and IL-10 promoter genes, respectively, and susceptibility to PSC. METHODS: TNF
      alpha -308 genotypes were studied by polymerase chain reaction (PCR) in 160 PSC
      patients from Norway and the UK compared with 145 ethnically matched controls. IL
      10 -627 genotypes were studied by PCR in 90 PSC patients compared with 84
      ethnically matched controls. RESULTS: A total of 16% of Norwegian PSC patients
      and 12% of British PSC patients were homozygous for the TNF2 allele compared with
      3% and 6% of respective controls. The TNF2 allele was present in 60% of PSC
      patients versus 30% of controls (OR(combined data)=3.2 (95% confidence intervals
      (CI) 1.8--4.5); p(corr)=10(-5)). The association between the TNF2 allele and
      susceptibility to PSC was independent of the presence of concurrent inflammatory
      bowel disease (IBD) in the PSC patients; 61% of PSC patients without IBD had TNF2
      compared with 30% of controls (OR(combined data)=3.2 (95% CI 1.2--9.0);
      p(corr)=0.006 ). There was no difference in the -627 IL-10 polymorphism
      distributions between patients and controls in either population. The increase in
      TNF2 allele in PSC patients only occurs in the presence of DRB1*0301 (DR3) and
      B8. In the combined population data, DRB1*0301 showed a stronger association with
      susceptibility to PSC than both the TNF2 and B8 alleles (OR(combined data)=3.8,
      p(corr)=10(-6) v OR(combined data)=3.2, p(corr)=10(-5) v OR(combined data )=3.41,
      p(corr)=10(-4), respectively). CONCLUSIONS: This study identified a significant
      association between possession of the TNF2 allele, a G-->A substitution at
      position -308 in the TNF-alpha promoter, and susceptibility to PSC. This
      association was secondary to the association of PSC with the A1-B8-DRB1*0301
      DQA1*0501-DQB1*0201 haplotype. No association was found between the IL-10 -627
      promoter polymorphism and PSC.

PMID- 11454809
TI  - International gastroenterology research: subject areas, impact, and funding.
AB  - AIMS: To examine the volume and potential impact of gastroenterology research
      outputs from 1985 to 1998 from 14 developed countries; the overlap with research
      in cancer, infectious diseases, and genetics; and the funding sources for this
      research. To determine if countries' research outputs correlated with their
      burden of corresponding diseases and inputs to their research. METHODS: Selective
      retrieval of papers from the Science Citation Index and manual look up of a
      sample to determine funding sources. Classification of journals by four
      categories of research level (clinical/basic) and potential impact (low/high).
      RESULTS: Gastroenterology represents about 8% of world biomedical research but
      over 11% in Italy, Japan, and Spain. Its potential impact is highest (but
      declining) for the USA. It has increased noticeably in most European countries,
      particularly in Finland. Gastroenterology research has become more clinical in
      Japan, Spain, Australia, and the Netherlands but more basic in Canada, Germany,
      Finland, Israel, and South Africa. Funding comes primarily from national
      governments, followed by national private non-profit sources and industry but
      little industrial funding occurs in some countries. There is a strong and
      positive correlation between reported deaths from gastrointestinal neoplasms and
      countries' outputs of research in gastrointestinal oncology. CONCLUSIONS:
      Bibliometric analysis can reveal differences between countries in their research
      in a subject when a common methodology is applied to an international database.
      Variations in research methods in different countries can plausibly explain some
      of the variation in the potential impact of the work.

PMID- 11454810
TI  - Angiotensin converting enzyme inhibitors and angiotensin II antagonists as
      therapy in chronic liver disease.

PMID- 11454811
TI  - Which PPI?

PMID- 11454816
TI  - Homocysteine: a novel risk factor for coronary heart disease in UK Indian Asians.

PMID- 11454817
TI  - How will the human genome project change cardiovascular medicine?

PMID- 11454818
TI  - Management of anticoagulants during pregnancy.

PMID- 11454819
TI  - Infective abdominal aortic aneurysm.

PMID- 11454820
TI  - Rheumatic heart disease: prevalence and preventive measures in the Indian
      subcontinent. Keywords: rheumatic heart disease; rheumatic fever.

PMID- 11454822
TI  - Stamps in cardiology: Down syndrome.

PMID- 11454821
TI  - Left sided arrhythmogenic ventricular dysplasia in siblings.
AB  - A 32 year old man with no previous medical history suffered a sudden cardiac
      death. Post mortem examination revealed circumferential fibro-fatty infiltration
      of the left ventricular myocardium. Histological appearance was characteristic of
      arrhythmogenic right ventricular dysplasia but unusual for its localisation only
      to the left ventricle. As a result of this sudden cardiac death the family of the
      deceased was screened for cardiac disease. A brother of the index case was 36
      years old and free of cardiac history and symptoms. Cardiac investigations
      revealed a functionally and electrically abnormal left ventricle with apparent
      sparing of the right ventricle. The brothers may have a left sided form of
      arrhythmogenic ventricular dysplasia and illustrate the importance of screening
      family members of young victims of sudden cardiac death.

PMID- 11454823
TI  - Impact of diabetes mellitus on long term survival after acute myocardial
      infarction in patients with single vessel disease.
AB  - OBJECTIVE: To assess the influence of diabetes on long term prognosis after
      reperfusion treatment and its interaction with multivessel disease. DESIGN: A
      retrospective observational study. SETTING: Hiroshima City Hospital. PATIENTS:
      1660 consecutive patients with acute myocardial infarction who underwent coronary
      angiography within 24 hours after the onset of chest pain. MAIN OUTCOME MEASURES:
      Influence of diabetes on 10 year survival after infarction was assessed using the
      generalised Wilcoxon test and Cox's proportional hazards regression. Follow up
      was completed in 1622 patients (98%). RESULTS: Diabetic patients had more
      multivessel disease than non-diabetic patients (53% v 34%, p < 0.001). When only
      patients with single vessel disease were compared, diabetes was associated with a
      reduced 10 year survival after infarction (p = 0.002). On the other hand, in
      patients with multivessel disease there was no significant difference in survival
      between diabetic and non-diabetic patients (p = 0.70). Multivariate analysis also
      showed that diabetes was an independent risk factor related to 10 year mortality
      after infarction in patients with single vessel disease (odds ratio (OR) 1.81,
      95% confidence interval (CI) 1.27 to 2.54; p = 0.001) and not in patients with
      multivessel disease (OR 1.17, 95% CI 0.85 to 1.60; p = 0.34). CONCLUSIONS:
      Diabetes is an independent predictor of long term mortality after infarction in
      patients with single vessel disease. However, in the presence of multivessel
      disease, prognosis after infarction is impaired regardless of diabetes, and the
      influence of diabetes is less obvious.

PMID- 11454824
TI  - Congenitally unguarded tricuspid orifice associated with underdeveloped pulmonary
      valve leaflets.

PMID- 11454826
TI  - Tricuspid valvectomy following tricuspid valve endocarditis on an intravenous
      drug addict.

PMID- 11454825
TI  - Raised urinary glucocorticoid and adrenal androgen precursors in the urine of
      young hypertensive patients: possible evidence for partial glucocorticoid
      resistance.
AB  - OBJECTIVE: To evaluate urinary glucocorticoid excretion profiles in a cohort of
      recently diagnosed young hypertensive patients. METHODS: After excluding patients
      with secondary causes, 60 individuals with premature hypertension were recruited
      (diagnosed by ambulatory blood pressure monitoring before the age of 36 years).
      In addition, 30 older hypertensive controls (age of onset > 36 years, "middle
      aged hypertensive controls"), and 30 normal controls (age matched to the young
      hypertensive group) were studied. All provided 24 hour urine collections for mass
      spectrometry for total cortisol metabolites and total androgen metabolites by gas
      chromatography. RESULTS: Among male patients, those with premature hypertension
      had higher total urinary excretion of cortisol metabolites (mean (SD), 13 332
      (6472) microg/day) than age matched normal controls (7270 (1788) microg/day; p =
      0.00001) or middle aged hypertensive controls (8315 (3565) microg/day; p =
      0.002). A similar increase was seen among the female patients, although the
      absolute concentrations were lower. There was no significant difference between
      middle aged hypertensive patients and normal controls. Urinary total androgen
      excretion profiles in female patients also showed an unusual increase in the
      premature hypertension group (2958 (1672) microg/day) compared with the other
      groups (middle aged hypertensive controls, 1373 (748) microg/day, p = 0.0003;
      normal controls, 1687 (636) microg/day, p = 0.002). In all subjects, serum sodium
      and creatinine concentrations were within the normal range; serum potassium
      concentrations were found to be low before the start of treatment. CONCLUSIONS:
      Individuals presenting with premature hypertension have an abnormally high
      excretion of glucocorticoid metabolites in the urine. While the mechanism remains
      uncertain, these findings are compatible with partial resistance of the
      glucocorticoid receptors, with a compensatory increase in cortisol and androgen
      metabolites. The mineralocorticoid effects of the latter (sodium and water
      retention) may contribute to an abnormally high blood pressure and may have
      implications for targeted selection of first line treatment in young hypertensive
      patients.

PMID- 11454827
TI  - Management and outcome of cardiogenic shock complicating acute myocardial
      infarction in hospitals with and without on-site catheterisation facilities.
AB  - OBJECTIVE: To determine whether the availability of on-site catheterisation and
      revascularisation facilities influenced hospital management and outcome of
      patients with acute myocardial infarction complicated by cardiogenic shock.
      METHODS: Patients with acute myocardial infarction were enrolled prospectively in
      four nationwide surveys during 1992, 1994, 1996, and 1998. The characteristics,
      management, and outcome of patients with cardiogenic shock were compared between
      hospitals with on-site catheterisation facilities (group 1; 18 hospitals) and
      without such facilities (group 2; 8 hospitals). RESULTS: Of 5351 patients with
      acute myocardial infarction, 254 (4.7%) developed cardiogenic shock. Group 1
      patients (n = 186 of 3854; 4.6%) were younger (mean (SD) age, 69.6 (12) v 73.7
      (10) years, p = 0.006) and had a lower proportion of women (36% v 52%, p = 0.03)
      than group 2 (n = 68 of 1243; 5.2%). There was no difference in other
      characteristics including the use of thrombolysis. Group 1 patients more often
      underwent coronary angiography (26% v 4%, p < 0.001), angioplasty (21% v 4%, p =
      0.002), and intra-aortic balloon counterpulsation (28% v 4%, p < 0.001). Seven
      day mortality was lower among group 1 than among group 2 patients (61% v 77%, p =
      0.02), even after age and sex adjustment (odds ratio (OR) 0.54; 95% confidence
      interval (CI) 0.28 to 1.02). This outcome benefit persisted at 30 days (74% v
      88%, p = 0.01; OR 0.45, 95% CI 0.18 to 0.98), and at 6 months (80% v 90%, p =
      0.06; OR 0.57, 95% CI 0.22 to 1.33). CONCLUSIONS: The greater use of invasive and
      interventional procedures in hospitals with catheterisation facilities is
      associated with improved survival of patients with acute myocardial infarction
      complicated by cardiogenic shock. Immediate availability of invasive care
      facilities will improve the outcome of cardiogenic shock in the community
      setting.

PMID- 11454828
TI  - Chronic thromboembolic pulmonary hypertension in a patient heterozygous for both
      factor V Leiden and G20210 prothrombin mutation.

PMID- 11454829
TI  - A simple benchmark for evaluating quality of care of patients following acute
      myocardial infarction.
AB  - OBJECTIVE: To develop a simple risk model as a basis for evaluating care of
      patients admitted with acute myocardial infarction. METHODS: From coronary care
      registers, biochemistry records and hospital management systems, 2153 consecutive
      patients with confirmed acute myocardial infarction were identified. With 30 day
      all cause mortality as the end point, a multivariable logistic regression model
      of risk was constructed and validated in independent patient cohorts. The areas
      under receiver operating characteristic curves were calculated as an assessment
      of sensitivity and specificity. The model was reapplied to a number of commonly
      studied subgroups for further assessment of robustness. RESULTS: A three variable
      model was developed based on age, heart rate, and systolic blood pressure on
      admission. This produced an individual probability of death by 30 days (P(30))
      where P(30) = 1/(1 + exp(-L(30))) and L(30) = -5.624 + (0.085 x age) + (0.014 x
      heart rate) - (0.022 x systolic blood pressure). The areas under the receiver
      operating characteristic curves for the reference and test cohorts were 0.79 (95%
      CI 0.76 to 0.82) and 0.76 (95% CI 0.72 to 0.79), respectively. To aid application
      of the model to routine clinical audit, a normogram relating observed mortality
      and sample size to the likelihood of a significant deviation from the expected 30
      day mortality rate was constructed. CONCLUSIONS: This risk model is simple,
      reproducible, and permits quality of care of acute myocardial infarction patients
      to be reliably evaluated both within and between centres.

PMID- 11454830
TI  - Increase in plasma adrenomedullin in patients with heart failure characterised by
      diastolic dysfunction.
AB  - OBJECTIVE: To investigate the relation between plasma adrenomedullin and the
      severity of diastolic dysfunction in patients with heart failure. DESIGN:
      Prospective study. SETTING: University teaching hospital. PATIENTS: 77 patients
      (mean (SEM) age 66.3 (1.2) years; 75% male) who were being followed in the
      outpatient clinic after admission to hospital for acute heart failure.
      INTERVENTIONS: Same day echocardiography with Doppler studies; determination of
      venous adrenomedullin concentration by radioimmunoassay. MAIN OUTCOME MEASURES:
      Plasma adrenomedullin concentration and its correlation with systolic and
      diastolic function. RESULTS: 31 patients (40%) had isolated diastolic dysfunction
      (ejection fraction > 50%), and the remaining 46 had a depressed ejection fraction
      (< 50%). Of the patients with diastolic dysfunction, 17 had a restrictive filling
      pattern. In all but one of these there was coexisting systolic failure (chi(2) =
      10.7, p = 0.001). Patients with systolic heart failure and a restrictive filling
      pattern (group 1, n = 16) had a higher plasma adrenomedullin than those with
      systolic failure and a non-restrictive filling pattern (group 2, n = 30) or with
      isolated diastolic heart failure and a non-restrictive filling pattern (group 3,
      n = 30) (mean (SEM): 91.7 (21.1) v 38.4 (8.8) v 34.0 (6.5) pmol/l, both p <
      0.05). All heart failure values were higher (p < 0.01) than the control value
      (6.9 (1.2) pmol/l). Ejection fraction and left ventricular dimensions were
      similar in groups 1 and 2. Plasma adrenomedullin did not correlate with ejection
      fraction or New York Heart Association functional class. Stepwise multiple
      regression analysis showed that the presence of a restrictive filling pattern was
      the only independent variable associated with a high plasma adrenomedullin.
      CONCLUSIONS: Plasma adrenomedullin concentrations in patients with heart failure
      are determined by the presence of diastolic dysfunction, and are especially
      raised in the presence of a restrictive filling pattern. There appears to be no
      correlation with systolic dysfunction.

PMID- 11454831
TI  - Pericardial constriction secondary to calcified intrapericardial haematoma.

PMID- 11454832
TI  - Prevalence of asymptomatic ST segment elevation in right precordial leads with
      right bundle branch block (Brugada-type ST shift) among the general Japanese
      population.
AB  - OBJECTIVE: To examine the modality and morbidity of asymptomatic ST segment
      elevation in leads V1 to V3 with right bundle branch block (Brugada-type ST
      shift). METHODS: 8612 Japanese subjects (5987 men and 2625 women, mean age 49.2
      years) who underwent a health check up in 1997 were investigated. Those with
      Brugada-type ST shift underwent the following further examinations over a two
      year period after the initial check up: ECG, echocardiogram, 24 hour Holter
      monitoring, treadmill exercise testing, signal averaged ECG, and slow kinetic
      sodium channel blocker loading test (cibenzoline, 1.4 mg/kg). RESULTS:
      Asymptomatic Brugada-type ST shift was found in 12 of 8612 (0.14%) subjects.
      Eleven of these 12 subjects were followed up. Follow up ECG exhibited persistent
      Brugada-type ST shift in seven of 11 (63.6%) subjects. ST shift was transformed
      from a saddle back to a coved type in three subjects. None of the subjects had
      morphological abnormalities or abnormal tachyarrhythmias. Positive late
      potentials were found in seven of 11 (63.6%) subjects. Augmentation of ST shift
      was shown by both submaximal exercise and drug administration in one of the 11
      subjects (9.1%). CONCLUSIONS: Asymptomatic subjects with Brugada-type ST shift
      were not unusual, at a rate of 0.14% in the general Japanese population. Almost
      all of the subjects had some abnormalities in non-invasive secondary
      examinations. Additional and prospective studies are needed to confirm the
      clinical significance and the prognosis of asymptomatic Brugada-type ST shift.

PMID- 11454833
TI  - Symptomatic improvement after radiofrequency catheter ablation for typical atrial
      flutter.
AB  - OBJECTIVE: To assess the changes in quality of life, arrhythmia symptoms, and
      hospital resource utilisation following catheter ablation of typical atrial
      flutter. DESIGN: Patient questionnaire to compare the time interval following
      ablation with a similar time interval before ablation. SETTING: Tertiary referral
      centre. PATIENTS: 63 consecutive patients were studied. Four patients
      subsequently underwent an ablate and pace procedure, two died of co-morbid
      illnesses, and two were lost to follow up. The remaining 55 patients form the
      basis of the report. RESULTS: Patients were followed for a mean (SD) of 12 (9.5)
      months. Atrial flutter ablation resulted in an improvement in quality of life
      (3.8 v 2.5, p < 0.001) and reductions in symptom frequency score (2.0 v 3.5, p <
      0.001) and symptom severity score (2.0 v 3.8, p < 0.001) compared with
      preablation values. There was a reduction in the number of patients visiting
      accident and emergency departments (11% v 53%, p < 0.001), requiring
      cardioversion (7% v 51%, p < 0.001), or being admitted to hospital for a rhythm
      problem (11% v 56%, p < 0.001). Subgroup analysis confirmed that patients with
      atrial flutter and concomitant atrial fibrillation before ablation and those with
      atrial flutter alone both derived significant benefit from atrial flutter
      ablation. Patients with concomitant atrial fibrillation had an improvement in
      quality of life (3.5 v 2.5, p < 0.001) and reductions in symptom frequency score
      (2.3 v 3.5, p < 0.001) and symptom severity score (2.2 v 3.7, p < 0.001) compared
      with preablation values. CONCLUSIONS: Ablation of atrial flutter is recommended
      both in patients with atrial flutter alone and in those with concomitant atrial
      fibrillation.

PMID- 11454834
TI  - Influence of slow coronary blood flow on stenosis morphology.

PMID- 11454835
TI  - Cross sectional study estimating prevalence of heart failure and left ventricular
      systolic dysfunction in community patients at risk.
AB  - OBJECTIVE: To examine a general practice population to measure the prevalence of
      signs and symptoms of heart failure (SSHF) and left ventricular systolic
      dysfunction (LVSD). DESIGN: Cross sectional screening study in three general
      practices followed by echocardiography. SETTING AND PATIENTS: All patients >/= 50
      years in two general practices and >/= 40 years in one general practice were
      screened by case record reviews and questionnaires (n = 2158), to identify
      subjects with some evidence of heart disease. Among these, subjects were sought
      who had SSHF (n = 115). Of 357 subjects with evidence of heart disease, 252 were
      eligible for examination, and 126 underwent further cardiological assessment,
      including 43 with SSHF. MAIN OUTCOME MEASURES: Prevalence of SSHF as defined by a
      modified Boston index, LVSD defined as an indirectly measured left ventricular
      ejection fraction </= 0.45, and numbers of subjects needing an echocardiogram to
      detect one case with LVSD. RESULTS: SSHF afflicted 0.5% of quadragenarians and
      rose to 11.7% of octogenarians. Two thirds were handled in primary care only. At
      >/= 50 years of age 6.4% had SSHF, 2.9% had LVSD, and 1.9% (95% confidence
      interval 1.3% to 2.5%) had both. To detect one case with LVSD in primary care, 14
      patients with evidence of heart disease without SSHF and 5.5 patients with SSHF
      had to be examined. CONCLUSION: SSHF is extremely prevalent in the community,
      especially in primary care, but more than two thirds do not have LVSD. The number
      of subjects with some evidence of heart disease needing an echocardiogram to
      detect one case of LVSD is 14.

PMID- 11454836
TI  - Echocardiographic features of Candida species endocarditis: 12 cases and a review
      of published reports.
AB  - OBJECTIVE: To describe the specific echocardiographic features of Candida species
      endocarditis. DESIGN: Retrospective review of the case records of patients with
      confirmed candida endocarditis. SETTING: Cases referred to three French
      university centres over an eight year period were studied. DESIGN: 12 patients
      with confirmed Candida species endocarditis infection were identified. The
      transthoracic (n = 12) and transoesophageal (n = 12) echocardiographic
      appearances were compared with the surgical findings (n = 10). RESULTS: Large
      dense heterogeneous vegetations were found in 11/12 cases. A hyperechogenic
      heterogeneous myocardial texture, observed in seven of the 12 patients, was
      associated with extensive myocardial damage at surgery. While it was possible to
      diagnose candidal cardiac infection in all patients by transthoracic
      echocardiography, transoesophageal echocardiography was useful for optimal
      assessment of the valvar and paravalvar structures. CONCLUSIONS: In the setting
      of endocarditis, the detection of myocardial involvement, which is characterised
      by a heterogeneous myocardial texture, is an argument in favour of Candida
      species endocarditis and may warrant early surgical intervention.

PMID- 11454837
TI  - Incremental shuttle walk test in the assessment of patients for heart
      transplantation.
AB  - OBJECTIVE: To compare the incremental shuttle walk test (ISWT) with treadmill
      exercise testing (TT) derived measurement of peak oxygen consumption (peak VO(2))
      in patients undergoing assessment for cardiac transplantation. DESIGN:
      Prospective comparison. All investigations occurred during a single period of
      admission for transplant assessment. SETTING: Single UK cardiothoracic
      transplantation unit. PATIENTS: 25 patients recruited (21 men). Mean age was 53
      years. INTERVENTIONS: Patients underwent two TT of peak VO(2) using the modified
      Naughton protocol and three (one practice) ISWT. Investigations were performed on
      consecutive days. MAIN OUTCOME MEASURES: Main outcome measures were repeatability
      of TT and ISWT assessments; relation between peak VO(2) and distance walked in
      the ISWT; and receiver operating characteristic (ROC) analysis to establish a
      distance walked in the ISWT that predicted which patients would have a peak VO(2)
      greater than 14 ml/min/kg. RESULTS: Both the ISWT and the TT were highly
      reproducible. Following the first practice walk, mean (SD) ISWT distances were
      400.0 (146) m (ISWT2) and 401.3 (129) m (ISWT3), r = 0.90, p < 0.0001. Mean peak
      VO(2) by TT was 15.2 (4.4) ml/kg/min (TT1) and 15.0 (4.4) ml/kg/min (TT2), r =
      0.83, p < 0.0001. The results revealed a strong correlation between distance
      covered in the ISWT and peak VO(2) obtained during TT (r = 0.73, p = 0.0001). ROC
      analysis showed that a distance walked of 450 m allowed the selection of patients
      with a peak VO(2) of over 14 ml/min/kg. CONCLUSIONS: This work confirms the
      utility of the ISWT in the assessment of exercise capacity in patients with
      severe heart failure undergoing assessment for cardiac transplantation. ISWT may
      provide a widely applicable surrogate measure for peak VO(2) estimation in this
      population. Shuttle distance walked may therefore allow the convenient, serial
      assessment of patients with heart failure before referral for transplantation.

PMID- 11454838
TI  - Coronary artery rupture treated with microcoil occlusion.

PMID- 11454839
TI  - Acute and chronic effects of surgical thromboendarterectomy on exercise capacity
      and ventilatory efficiency in patients with chronic thromboembolic pulmonary
      hypertension.
AB  - OBJECTIVE: To assess acute and chronic effects of surgical thromboendarterectomy
      on exercise capacity and ventilatory efficiency in patients with chronic
      thromboembolic pulmonary hypertension (CTEPH). DESIGN: Cardiopulmonary exercise
      testing was performed in 20 patients with CTEPH before thromboendarterectomy
      (baseline), one month after (early phase), and four months after (late phase).
      Peak oxygen uptake (peak VO(2)) and the ventilatory response to carbon dioxide
      production (VE-VCO(2) slope) were measured for assessment of exercise capacity
      and ventilatory efficiency. Right heart catheterisation was performed in all
      patients before and one month after surgery. RESULTS: Baseline peak VO(2)
      decreased and VE-VCO(2) slope increased along with the increase in pulmonary
      vascular resistance in patients with CTEPH. After thromboendarterectomy, the VE
      VCO(2) slope decreased greatly from baseline to the early phase (mean (SD), 50
      (9) to 37 (7), p < 0.05) and reached a steady level thereafter. In contrast, a
      continued increase in peak VO(2) was noted from the early to the late phase (16.9
      (4.1) to 21.1 (5.0) ml/kg/min, p < 0.05). The decrease in the VE-VCO(2) slope
      from baseline to the early phase, but not the increase in peak VO(2), correlated
      strongly with the decrease in pulmonary vascular resistance after surgery (r =
      0.75, p < 0.01). CONCLUSIONS: Thromboendarterectomy may cause an immediate
      improvement in ventilatory efficiency, possibly through its beneficial
      haemodynamic effects. In contrast, exercise capacity may continue to improve
      towards the late phase, reflecting peripheral adaptation to exercise.

PMID- 11454840
TI  - Uncomplicated moderate coronary artery dissections after balloon angioplasty:
      good outcome without stenting.
AB  - OBJECTIVE: To study the relation between moderate coronary dissections, coronary
      flow velocity reserve (CFVR), and long term outcome. METHODS: 523 patients
      undergoing balloon angioplasty and sequential intracoronary Doppler measurements
      were examined as part of the DEBATE II trial (Doppler endpoints balloon
      angioplasty trial Europe). After successful balloon angioplasty, patients were
      randomised to stenting or no further treatment. Dissections were graded at the
      core laboratory by two observers and divided into four categories: none, mild
      (type A-B), moderate (type C), severe (types D to F). Patients with severe
      dissections (n = 128) or without available reference vessel CFVR (n = 139) were
      excluded. The remaining 256 patients were divided into two groups according to
      the presence (group A, n = 45) or absence (group B, n = 211) of moderate
      dissection. RESULTS: Following balloon angioplasty, there was no difference in
      CFVR between the two groups. At 12 months follow up, a higher rate of major
      adverse cardiac events was observed overall in group A than in group B (10 (22%)
      v 23 (11%), p = 0.041). However, the risk of major adverse events was similar in
      the subgroups receiving balloon angioplasty (group A, 6 (19%) v group B, 16
      (16%), NS). Among group A patients, the adverse events risk was greater in those
      randomised to stenting (odds ratios 6.603 v 1.197, p = 0.046), whereas there was
      no difference in risk if the group was analysed according to whether the CFVR was
      < 2.5 or >/= 2.5 after balloon angioplasty. CONCLUSIONS: Moderate dissections
      left untreated result in no increased risk of major adverse cardiac events.
      Additional stenting does not improve the long term outcome.

PMID- 11454841
TI  - Obliteration of a coronary artery aneurysm with a covered coronary stent.

PMID- 11454842
TI  - Comparison of formulae for heart rate correction of QT interval in exercise ECGs
      from healthy children.
AB  - OBJECTIVE: To investigate the differences in four formulae for heart rate
      correction of the QT interval in serial ECG recordings in healthy children
      undergoing a graded exercise test. SUBJECTS: 54 healthy children, median age 9.9
      years (range 5.05-14.9 years), subjected to graded physical exercise (on a
      bicycle ergometer or treadmill) until heart rate reached > 85% of expected
      maximum for age. DESIGN: ECG was recorded at baseline, at maximum exercise, and
      at one, two, four, and six minutes after exercise. For each stage, a 12 lead
      digital ECG was obtained and printed. In each ECG, QT and RR interval were
      measured (lead II), heart rate was calculated, and QTc values were obtained using
      the Bazett, Hodges, Fridericia, and Framingham formulae. A paired t test was used
      for comparison of QTc, QT, and RR interval at rest and peak exercise, and
      analysis of variance for all parameters for different stages for each formula.
      RESULTS: From peak exercise to two minutes recovery there was a delay in QT
      lengthening compared with RR lengthening, accounting for differences observed
      with the formulae after peak exercise. At peak exercise, the Bazett and Hodges
      formulae led to prolongation of QTc intervals (p < 0.001), while the Fridericia
      and Framingham formulae led to shortening of QTc intervals (p < 0.001) until four
      minutes of recovery. The Bazett QTc shortened significantly at one minute after
      peak exercise. CONCLUSIONS: The practical meaning of QT interval measurements
      depends on the correction formula used. In studies investigating repolarisation
      changes (for example, in the long QT syndromes, congenital heart defects, or in
      the evaluation of new drugs), the use of an ad hoc selected heart rate correction
      formula may bias the results in either direction. The Fridericia and Framingham
      QTc values at one minute recovery from exercise may be useful in the assessment
      of long QT syndromes.

PMID- 11454843
TI  - Abnormalities of right ventricular long axis function after atrial repair of
      transposition of the great arteries.
AB  - BACKGROUND: While volume derived global indices of right ventricle (RV) function
      are frequently abnormal after the Mustard procedure, the mechanism for these
      abnormalities is poorly understood. RV muscle fibres are predominantly arranged
      longitudinally and thus indices derived in the long axis may better describe RV
      function. METHODS: 20 survivors of the Mustard operation were studied (age 7.8
      37.3 years, median 14.2 years). Long axis recordings from the apical four chamber
      view were obtained with the M mode cursor positioned through the lateral angle of
      the tricuspid valve annulus. M mode traces were recorded on paper and later
      digitised to derive total atrioventricular ring excursion, peak lengthening rate,
      and peak shortening rate. These data were averaged and compared with control data
      for the normal RV and left ventricle (LV). RESULTS: RV total atrioventricular
      ring excursion was lower than that for the RV (p < 0.0001) or LV (p < 0.005) of
      controls. Peak lengthening rate was lower than the normal RV (p < 0.0001) and LV
      (p < 0.0001) rates. Furthermore, peak shortening rate was less than that of
      normal RV (p < 0.0001) and normal LV (p < 0.005) controls. CONCLUSION: Systemic
      RV long axis function is notably reduced compared with that of either the normal
      subpulmonary RV or the systemic LV. This presumably reflects the response of the
      predominantly longitudinally arranged myocardial fibres to increased afterload.
      However, such measurements may provide a more sensitive marker for progressive
      changes in global function during long term follow up.

PMID- 11454844
TI  - Left atrial myxoma supplied from the right coronary artery.

PMID- 11454845
TI  - Relation between coronary artery remodelling (compensatory dilatation) and
      stenosis in human native coronary arteries.
AB  - OBJECTIVES: To investigate the contribution of plaque size and vessel remodelling
      to coronary artery stenosis and to assess the role of vessel shrinkage (negative
      remodelling) across a wide range of lesions. DESIGN: Postmortem study of coronary
      remodelling in perfusion fixed hearts. SUBJECTS: 24 men and 24 women who died
      suddenly with coronary artery disease. MAIN OUTCOME MEASURES: Percentage
      stenosis, percentage plaque burden, percentage remodelling, and arc of normal
      vessel were measured and related to age, sex, smoking status, and history of
      hypertension. RESULTS: There was a positive relation between percentage stenosis
      and percentage plaque burden (r = 0.6, p < 0.0001) and an inverse relation
      between percentage stenosis and percentage remodelling (r = -0.4, p < 0.0001).
      Multilinear regression modelling showed that luminal stenosis = 1.0 (plaque
      burden) - 0.4 (vessel remodelling). Remodelling was greater in lesions that would
      not have been significant at angiography (</= 25% stenosis) than in the remaining
      lesions (25.9 (26)% v 10.0 (21.1)%, p < 0.0001, respectively) and was reduced in
      segments with circumferential plaques (12.7 (24.5)% v 20.7 (24.3)% in eccentric
      plaques, p = 0.001). Remodelling did not correlate with age, sex, or smoking.
      Negative remodelling was present in 62 lesions with a stenosis > 25% versus 10
      lesions with </= 25% stenosis (p < 0.0001). Lesions with negative remodelling had
      greater plaque burden and luminal stenosis and a reduced arc of normal segment.
      CONCLUSION: Outward arterial remodelling negates the stenosing effect of
      increasing plaque size. Significant coronary stenoses arise from a failure of
      this outward remodelling in the face of a large plaque burden. Coronary arterial
      remodelling is unrelated to sex or smoking and is plaque specific.

PMID- 11454846
TI  - Magnesium causes nitric oxide independent coronary artery vasodilation in humans.
AB  - OBJECTIVE: To determine how magnesium affects human coronary arteries and whether
      endothelium derived nitric oxide (EDNO) is involved in the coronary arterial
      response to magnesium. DESIGN: Quantitative coronary angiography and Doppler flow
      velocity measurements were used to determine the effects of the nitric oxide
      synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on magnesium induced
      dilation of the epicardial and resistance coronary arteries. SETTING: Hiroshima
      University Hospital a tertiary cardiology centre. PATIENTS: 17 patients with
      angiographically normal coronary arteries. INTERVENTIONS: Magnesium sulfate
      (MgSO(4)) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the
      left coronary ostium before and after intracoronary infusion of L-NMMA. MAIN
      OUTCOME MEASURES: Diameter of the proximal and distal segments of the epicardial
      coronary arteries and coronary blood flow. RESULTS: At a dose of 0.02 mmol/min,
      MgSO(4) did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO(4)
      caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11
      (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood
      flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 v baseline for all). MgSO(4)
      increased the changes in these parameters after the infusion of L-NMMA (p < 0.001
      v baseline). CONCLUSIONS: Magnesium dilates both the epicardial and resistance
      coronary arteries in humans. Furthermore, the coronary arterial response to
      magnesium is dose dependent and independent of EDNO.

PMID- 11454847
TI  - Renin angiotensin system inhibition is associated with reduced free radical
      concentrations in arteries of patients with coronary heart disease.

PMID- 11454848
TI  - Strong prognostic value of combining N-terminal atrial natriuretic peptide and
      ECG to predict death in heart patients from general practice.

PMID- 11454849
TI  - Docetaxel induced cardiotoxicity.

PMID- 11454850
TI  - Implementation of the NICE guidelines for the primary prevention of mortality
      from ventricular tachyarrhythmias: implications for UK electrophysiology centres;
      activity modelling from the UK-HEART study.

PMID- 11454851
TI  - Implantable cardioverter-defibrillators.

PMID- 11454852
TI  - Diseases of the thoracic aorta.

PMID- 11454853
TI  - Management of pericardial effusion.

PMID- 11454854
TI  - The absence of activator protein 1-dependent gene expression in THP-1 macrophages
      stimulated with phorbol esters is due to lack of p38 mitogen-activated protein
      kinase activation.
AB  - Activator protein 1 (AP-1) binds to the promoters of many genes involved in
      immune and inflammatory responses. We have previously shown that the p38 mitogen
      activated protein (MAP) kinase regulates NF-kappa B-dependent gene expression by
      modulating the phosphorylation and subsequent activation of TATA-binding protein
      (TBP). In this study, we asked whether the p38 MAP kinase regulated the
      transcriptional activity of AP-1. We found that phorbol 12-myristate 13-acetate
      (PMA) was unable to drive the AP-1-dependent reporter gene in THP-1 cells. PMA
      activated both the extracellular signal-regulated kinase and c-Jun NH(2)-terminal
      kinase MAP kinases, but it did not activate the p38 MAP kinase. We found that
      cells expressing MAP kinase kinase 6(Glu), which is the upstream kinase that
      activates the p38 MAP kinase, had significantly increased AP-1-dependent gene
      expression alone and when stimulated with PMA. These cells also had increased
      phosphorylation of native c-Jun, suggesting that both c-Jun NH(2)-terminal kinase
      and p38 MAP kinases phosphorylate c-Jun. More importantly, expression of a
      constitutive active MAP kinase kinase 6(Glu) resulted in the phosphorylation of a
      His-TBP fusion protein and increased direct interaction of TBP with c-Jun. These
      findings suggest that in macrophages, the p38 MAP kinase regulates AP-1-driven
      transcription by modulating the activation of TBP.

PMID- 11454855
TI  - Strong RNA splicing enhancers identified by a modified method of cycled selection
      interact with SR protein.
AB  - A modified method of cycled selection was used to characterize splicing enhancers
      for exon inclusion from a pool of beta-globin-based three exon/two intron pre
      mRNAs with a variable number of random nucleotides incorporated in the internal
      exon. The pre-mRNAs generated by this method contained random sequences ranging
      from 0 to 18 nucleotides in length. This method was used to isolate particular
      splicing enhancer motifs from a previously enriched pool of extremely diverse
      enhancers. After four cycles of selection for mRNA containing the internal exon,
      a distinct enhancer motif (GACGAC...CAGCAG) was highly enriched. This motif
      served as strong splicing enhancers in a heterogeneous exon. We have shown here
      that the selected enhancer motif promotes exon inclusion through specific
      interaction with SRp30. We have also shown that although present in many of our
      selected splicing enhancers conforming to this motif, a typical purine-rich
      enhancer sequence is dispensable for either enhancer activity or binding with
      SRp30.

PMID- 11454856
TI  - Nuclear retention of ATM at sites of DNA double strand breaks.
AB  - The ATM protein kinase mediates a rapid induction of cellular responses to DNA
      double strand breaks (DSBs). ATM kinase activity is enhanced immediately after
      exposure of cells to DSB-inducing agents, but no changes in its amount or
      subcellular location following that activation have been reported. We speculated
      that some of the ATM molecules associate with sites of DSBs, while the rest of
      the nuclear ATM pool remains in the nucleoplasm, masking detection of the damage
      associated ATM fraction. Using detergent extraction to remove nucleoplasmic
      proteins, we show here that immediately following induction of DSBs, a fraction
      of the ATM pool becomes resistant to extraction and is detected in nuclear
      aggregates. Colocalization of the retained ATM with the phosphorylated form of
      histone H2AX (gamma-H2AX) and with foci of the Nbs1 protein suggests that ATM
      associates with sites of DSBs. The striking correlation between the appearance of
      retained ATM and of gamma-H2AX, and the rapid association of a fraction of ATM
      with gamma-H2AX foci, are consistent with a major role for ATM in the early
      detection of DSBs and subsequent induction of cellular responses.

PMID- 11454857
TI  - Side chain hydroxylations in bile acid biosynthesis catalyzed by CYP3A are
      markedly up-regulated in Cyp27-/- mice but not in cerebrotendinous xanthomatosis.
AB  - The accumulation of various 25-hydroxylated C(27)-bile alcohols in blood and
      their excretion in urine are characteristic features of cerebrotendinous
      xanthomatosis (CTX) a recessively inherited inborn error of bile acid synthesis
      caused by mutations in the mitochondrial sterol 27-hydroxylase (CYP27) gene.
      These bile alcohols may be intermediates in the alternative cholic acid side
      chain cleavage pathway. The present study was undertaken to identify enzymes and
      reactions responsible for the formation of these bile alcohols and to explain why
      Cyp27(-/-) mice do not show CTX-related abnormalities. Microsomal activities of
      5beta-cholestane-3alpha,7alpha,12alpha-triol 25- and 26-hydroxylases, 5beta
      cholestane-3alpha,7alpha,12alpha,25-tetrol 23R-, 24S-, and 27-hydroxylases and
      testosterone 6beta-hydroxylase, a marker enzyme for CYP3A, in Cyp27(-/-) mice
      livers were markedly up-regulated (5.5-, 3.5-, 6.5-, 7.5-, 2.9-, and 5.4-fold,
      respectively). In contrast, these enzyme activities were not increased in CTX.
      The activities of 5beta-cholestane-3alpha,7alpha,12alpha-triol 25- and 26
      hydroxylases and 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol 23R-, 24R-, 24S
      , and 27-hydroxylases were strongly correlated with the activities of
      testosterone 6beta-hydroxylase in control human liver microsomes from eight
      unrelated donors. Troleandomycin, a specific inhibitor of CYP3A, markedly
      suppressed these microsomal side chain hydroxylations in both mouse and human
      livers in a dose-dependent manner. In addition, experiments using recombinant
      overexpressed human CYP3A4 confirmed that these microsomal side chain
      hydroxylations were catalyzed by a single enzyme, CYP3A4. The results demonstrate
      that microsomal 25- and 26-hydroxylations of 5beta-cholestane
      3alpha,7alpha,12alpha-triol and microsomal 23R-, 24R-, 24S-, and 27
      hydroxylations of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol are mainly
      catalyzed by CYP3A in both mice and humans. Unlike Cyp27(-/-) mice, CYP3A
      activity was not up-regulated despite marked accumulation of 5beta-cholestane
      3alpha,7alpha,12alpha-triol in CTX.

PMID- 11454858
TI  - An extra nucleotide in the consensus catalytic core of a viroid hammerhead
      ribozyme: implications for the design of more efficient ribozymes.
AB  - Hammerhead ribozymes catalyze self-cleavage of oligomeric RNAs generated in
      replication of certain viroid and viroid-like RNAs. Previous studies have defined
      a catalytic core conserved in most natural hammerheads, but it is still unknown
      why some present deviations from the consensus. We have addressed this issue in
      chrysanthemum chlorotic mottle viroid (CChMVd), whose (+) hammerhead has an extra
      A (A10) between the conserved A9 and the quasi-conserved G10.1. Effects of
      insertions at this position on hammerhead kinetics have not hitherto been
      examined. A10 caused a moderate decrease of the trans-cleaving rate constant with
      respect to the CChMVd (+) hammerhead without this residue, whereas A10-->C and
      A10-->G substitutions had major detrimental effects, likely because they favor
      catalytically inactive foldings. By contrast, A10-->U substitution induced a 3-4
      fold increase of the rate constant, providing an explanation for the extra U10
      present in two natural hammerheads. Because A10 also occupies a singular and
      indispensable position in the global CChMVd conformation, as revealed by
      bioassays, these results show that some hammerheads deviate from the consensus
      due to the involvement of certain residues in critical function(s) other than
      self-cleavage. Incorporation of the extra U10 into a model hammerhead also caused
      a similar increase in the rate constant, providing data for a deeper
      understanding of the hammerhead structural requirements and for designing more
      efficient ribozymes.

PMID- 11454859
TI  - The plant zinc finger protein ZPT2-2 has a unique mode of DNA interaction.
AB  - ZPT2-2 is a DNA-binding protein of petunia that contains two canonical TFIIIA
      type zinc finger motifs separated by a long linker. We previously reported that
      ZPT2-2 bound to two separate AGT core sites, with each zinc finger making contact
      with each core site. Here we present our further characterization of ZPT2-2 by
      using selected and amplified binding sequence imprinting and surface plasmon
      resonance analyses; together, these assays revealed some unusual features of the
      interaction between ZPT2-2 and DNA. These experiments allowed us to conclude that
      1) the optimal binding sequence for the N-terminal zinc finger is AGC(T), and
      that of the C-terminal one is CAGT; 2) multiple arrangements of the two core
      sites accommodate binding; and 3) the spacing between the two core sites affects
      the binding affinity. In light of these observations, we propose a new model for
      the DNA-ZPT2-2 interaction. Further, consistent with this model, a high affinity
      binding site for ZPT2-2 was found in the promoter region of the ZPT2-2 gene. This
      site may serve as a cis-element for the autoregulation of ZPT2-2 gene expression.

PMID- 11454860
TI  - Role of the C-terminal residue of the DNA polymerase of bacteriophage T7.
AB  - The crystal structure of the DNA polymerase encoded by gene 5 of bacteriophage
      T7, in a complex with its processivity factor, Escherichia coli thioredoxin, a
      primer-template, and an incoming deoxynucleoside triphosphate reveals a putative
      hydrogen bond between the C-terminal residue, histidine 704 of gene 5 protein,
      and an oxygen atom on the penultimate phosphate diester of the primer strand.
      Elimination of this electrostatic interaction by replacing His(704) with alanine
      renders the phage nonviable, and no DNA synthesis is observed in vivo. Polymerase
      activity of the genetically altered enzyme on primed M13 DNA is only 12% of the
      wild-type enzyme, and its processivity is drastically reduced. Kinetic parameters
      for binding a primer-template (K(D)(app)), nucleotide binding (K(m)), and k(off)
      for dissociation of the altered polymerase from a primer-template are not
      significantly different from that of wild-type T7 DNA polymerase. However, the
      decrease in polymerase activity is concomitant with increased hydrolytic
      activity, judging from the turnover of nucleoside triphosphate into the
      corresponding nucleoside monophosphate (percentage of turnover, 65%) during DNA
      synthesis. Biochemical data along with structural observations imply that the
      terminal amino acid residue of T7 DNA polymerase plays a critical role in
      partitioning DNA between the polymerase and exonuclease sites.

PMID- 11454861
TI  - Distinct MutS DNA-binding modes that are differentially modulated by ATP binding
      and hydrolysis.
AB  - The role of MutS ATPase in mismatch repair is controversial. To clarify further
      the function of this activity, we have examined adenine nucleotide effects on
      interactions of Escherichia coli MutS with homoduplex and heteroduplex DNAs. In
      contrast to previous results with human MutS alpha, we find that a physical block
      at one end of a linear heteroduplex is sufficient to support stable MutS complex
      formation in the presence of ATP.Mg(2+). Surface plasmon resonance analysis at
      low ionic strength indicates that the lifetime of MutS complexes with
      heteroduplex DNA depends on the nature of the nucleotide present when MutS binds.
      Whereas complexes prepared in the absence of nucleotide or in the presence of ADP
      undergo rapid dissociation upon challenge with ATP x Mg(2+), complexes produced
      in the presence of ATP x Mg(2+), adenosine 5'-(beta,gamma-imino)triphosphate
      (AMPPNP) x Mg(2+), or ATP (no Mg(2+)) are resistant to dissociation upon ATP
      challenge. AMPPNP x Mg(2+) and ATP (no Mg(2+)) reduce MutS affinity for
      heteroduplex but have little effect on homoduplex affinity, resulting in
      abolition of specificity for mispaired DNA at physiological salt concentrations.
      Conversely, the highest mismatch specificity is observed in the absence of
      nucleotide or in the presence of ADP. ADP has only a limited effect on
      heteroduplex affinity but reduces MutS affinity for homoduplex DNA.

PMID- 11454862
TI  - Ceramide inhibits axonal growth and nerve growth factor uptake without
      compromising the viability of sympathetic neurons.
AB  - Ceramide inhibits axonal growth of cultured rat sympathetic neurons when the
      ceramide content of distal axons, but not cell bodies, is increased (Posse de
      Chaves, E. I., Bussiere, M. Vance, D. E., Campenot, R. B., and Vance, J.E. (1997)
      J. Biol. Chem. 272, 3028-3035). We now report that inhibition of growth does not
      result from cell death since although ceramide is a known apoptotic agent, C(6)
      ceramide given to the neurons for 24 h did not cause cell death but instead
      protected the neurons from death induced by deprivation of nerve growth factor
      (NGF). We also find that a pool of ceramide generated from sphingomyelin in
      distal axons, but not cell bodies, inhibits axonal growth. Analysis of endogenous
      sphingomyelinase activities demonstrated that distal axons are rich in neutral
      sphingomyelinase activity but contain almost no acidic sphingomyelinase, which is
      concentrated in cell bodies/proximal axons. Together, these observations are
      consistent with the idea that generation of ceramide from sphingomyelin by a
      neutral sphingomyelinase in axons inhibits axonal growth. Furthermore, we
      demonstrate that treatment of distal axons with ceramide inhibits the uptake of
      NGF and low density lipoproteins by distal axons by approximately 70 and 40%,
      respectively, suggesting that the inhibition of axonal growth by ceramide might
      be due, at least in part, to impaired endocytosis of NGF. However, inhibition of
      endocytosis of NGF by ceramide could not be ascribed to decreased phosphorylation
      of TrkA.

PMID- 11454863
TI  - Inhibition of p53 transcriptional activity by the S100B calcium-binding protein.
AB  - The levels of S100 Ca(2+)-binding proteins correlate with the progression of
      certain tumors, but their role, if any, in carcinogenesis is still poorly
      understood. S100B protein associates with both the p53 oligomerization domain
      (residues 325-355) and the extreme C terminus of the tumor suppressor p53
      (residues 367-392). Consequently, S100B inhibits p53 tetramer formation and p53
      phosphorylation mediated by protein kinase C, on p53 C-terminal end. In this
      report, we show that the S100B protein decreases p53 DNA binding and
      transcriptional activity. The effect of S100B is reflected in vivo by a reduced
      accumulation of p53, p21, and MDM2 protein levels in co-transfection assays and
      in response to bleomycin. The S100B can still interact with p53 in the absence of
      p53 extreme C-terminal end and reduce the expression of p53 downstream effector
      genes. These data indicate that S100B does not require p53 extreme C-terminal end
      to inhibit p53 activity. Collectively, these findings imply that elevated levels
      of S100B in tumors such as astrocytomas and gliomas could inhibit p53 functions
      and contribute to cancer progression.

PMID- 11454864
TI  - Phosphorylation of Mcm4 at specific sites by cyclin-dependent kinase leads to
      loss of Mcm4,6,7 helicase activity.
AB  - Mcm proteins that play an essential role in eukaryotic DNA replication are
      phosphorylated in vivo, and cyclin-dependent protein kinase is at least in part
      responsible for the phosphorylation of Mcm4. Our group reported that the DNA
      helicase activity of Mcm4,6,7 complex, which may be involved in initiation of DNA
      replication, is inhibited following phosphorylation by Cdk2/cyclin A in vitro.
      Here, we further examined the interplay between mouse Mcm4,6,7 complex and cyclin
      dependent kinases and determined the sites required for the phosphorylation of
      Mcm4. Six Ser and Thr residues, in all, were required for the phosphorylation.
      Inhibition of Mcm4,6,7 helicase activity by Cdk2/cyclin A was largely relieved by
      introducing mutations in these residues of Mcm4. Anti-phosphothreonine antibodies
      raised against one of these sites reacted with Mcm4 prepared from HeLa cells at
      mitotic phase but did not bind to those at G(1) and G(1)/S, suggesting that this
      site is mainly phosphorylated in the mitotic phase. Mcm4,6,7 complex purified
      from HeLa cells at the mitotic phase exhibited a low level of DNA helicase
      activity, compared with the complexes prepared from cells at other phases. These
      results suggest that phosphorylation of Mcm4 at specific sites leads to loss of
      Mcm4,6,7 DNA helicase activity.

PMID- 11454865
TI  - Dual control of replication timing. Stochastic onset but programmed completion of
      mammalian chromosome duplication.
AB  - In mammalian cells, DNA replication proceeds according to a precise temporal
      order during the S phase, but how this program is controlled remains poorly
      understood. We analyzed the replication-dependent bromodeoxyuridine banding of
      chromosomes in Chinese hamster cells treated with the spindle poison nocodazole.
      In these cells, nocodazole induces a transient mitotic arrest, followed by DNA re
      replication without intervening cell division. Nuclear fragmentation is often
      observed in tetraploid derivatives, and previous studies suggest that replication
      timing of chromosomes could be affected when they are segregated into different
      micronuclei. Here we show that the onset of replication is frequently
      asynchronous on individual chromosomes during the re-replication process.
      Moreover, fluorescence in situ hybridization analysis revealed that replication
      synchrony is equally altered in fragmented and non-fragmented nuclei, indicating
      that asynchronous onset of replication is not dependent on physical separation of
      the chromosomes into isolated compartments. We also show that the ordered program
      of replication is always preserved along individual chromosomes. Our results
      demonstrate that the onset of replication of individual chromosomes in the same
      nuclear compartment can be uncoupled from the time of S-phase entry and from the
      programmed replication of chromosome sub-domains, revealing that multi-level
      controls contribute to establish replication timing in mammalian cells.

PMID- 11454866
TI  - Tamoxifen activates smooth muscle BK channels through the regulatory beta 1
      subunit.
AB  - Estrogen (17beta-estradiol; 17betaE) and xenoestrogens, estrogenic compounds that
      are not steroid hormones, have non-genomic actions at plasma membrane receptors
      unrelated to the nuclear estrogen receptor. The open probability (P(o)) of large
      conductance Ca(2+)/voltage-sensitive k(+)(BK) channels is increased by 17betaE
      through the regulatory beta1 subunit. The pharmacological nature of the putative
      membrane binding site is unclear. We probed the site by determining whether
      tamoxifen ((Z)-1-(p-dimethylaminoethoxy-phenyl)-1,2-diphenyl-1-butene; Tx), a
      chemotherapeutic xenoestrogen, increased P(o) in clinically relevant
      concentrations (0.1-10 microm). In whole cell patch clamp recordings on canine
      colonic myocytes, which express the beta1 subunit, Tx activated charybdotoxin
      sensitive K(+) current. In single channel experiments, Tx increased the NP(o)
      (P(o) x number channels; N) and decreased the unitary conductance (gamma) of BK
      channels. Tx increased NP(o) (EC(50) = 0.65 microm) in excised membrane patches
      independent of Ca(2+) changes. The Tx mechanism of action requires the beta1
      subunit, as Tx increased the NP(o) of Slo alpha expressed in human embryonic
      kidney cells only in the presence of the beta1 subunit. Tx decreased gamma of the
      alpha subunit expressed alone, without effect on NP(o). Our data indicate that Tx
      increases BK channel activity in therapeutic concentrations and reveal novel
      pharmacological properties attributable to the alpha and beta1 subunits. These
      data shed light on BK channel structure and function, non-genomic mechanisms of
      regulation, and physiologically and therapeutically relevant effects of
      xenoestrogens.

PMID- 11454867
TI  - Homologous pairing promoted by the human Rad52 protein.
AB  - The Rad52 protein, which is unique to eukaryotes, plays important roles in the
      Rad51-dependent and the Rad51-independent pathways of DNA recombination. In the
      present study, we have biochemically characterized the homologous pairing
      activity of the HsRad52 protein (Homo sapiens Rad52) and found that the
      presynaptic complex formation with ssDNA is essential in its catalysis of
      homologous pairing. We have identified an N-terminal fragment (amino acid
      residues 1-237, HsRad52(1-237)) that is defective in binding to the human Rad51
      protein, which catalyzed homologous pairing as efficiently as the wild type
      HsRad52. Electron microscopic visualization revealed that HsRad52 and HsRad52(1
      237) both formed nucleoprotein filaments with single-stranded DNA. These lines of
      evidence suggest the role of HsRad52 in the homologous pairing step of the Rad51
      independent recombination pathway. Our results reveal the striking similarity
      between HsRad52 and the Escherichia coli RecT protein, which functions in a RecA
      independent recombination pathway.

PMID- 11454868
TI  - Chromatin remodeling by the thyroid hormone receptor in regulation of the thyroid
      stimulating hormone alpha-subunit promoter.
AB  - The chromatin architecture of a promoter is an important determinant of its
      transcriptional response. For most target genes, the thyroid hormone receptor
      (TR) activates gene expression in response to thyroid hormone (T(3)). In
      contrast, the thyroid-stimulating hormone alpha-subunit (TSH alpha) gene promoter
      is down-regulated by TR in the presence of T(3). Here we utilize the capacity for
      the Xenopus oocyte to chromatinize exogenous nuclear- injected DNA to analyze the
      chromatin architecture of the TSH alpha promoter and how this changes upon TR
      mediated regulation. Interestingly, in the oocyte, the TSH alpha promoter was
      positively regulated by T(3). In the inactive state, the promoter contained six
      loosely positioned nucleosomes. The addition of TR/retinoid X receptor together
      had no effect on the chromatin structure, but the inclusion of T(3) induced
      strong positioning of a dinucleosome in the TSH alpha proximal promoter that was
      bordered by regions that were hypersensitive to cleavage by methidiumpropyl EDTA.
      We identified a novel thyroid response element that coincided with the proximal
      hypersensitive region. Furthermore, we examined the consequences of mutations in
      TR that impaired coactivator recruitment. In a comparison with the Xenopus TR
      beta A promoter, we found that the effects of these mutations on transactivation
      and chromatin remodeling were significantly more severe on the TSH alpha
      promoter.

PMID- 11454869
TI  - The major antenna complex of photosystem II has a xanthophyll binding site not
      involved in light harvesting.
AB  - We have characterized a xanthophyll binding site, called V1, in the major light
      harvesting complex of photosystem II, distinct from the three tightly binding
      sites previously described as L1, L2, and N1. Xanthophyll binding to the V1 site
      can be preserved upon solubilization of the chloroplast membranes with the mild
      detergent dodecyl-alpha-d-maltoside, while an IEF purification step completely
      removes the ligand. Surprisingly, spectroscopic analysis showed that when bound
      in this site, xanthophylls are unable to transfer absorbed light energy to
      chlorophyll a. Pigments bound to sites L1, L2, and N1, in contrast, readily
      transfer energy to chlorophyll a. This result suggests that this binding site is
      not directly involved in light harvesting function. When violaxanthin, which in
      normal conditions is the main carotenoid in this site, is depleted by the de
      epoxidation in strong light, the site binds other xanthophyll species, including
      newly synthesized zeaxanthin, which does not induce detectable changes in the
      properties of the complex. It is proposed that this xanthophyll binding site
      represents a reservoir of readily available violaxanthin for the operation of the
      xanthophyll cycle in excess light conditions.

PMID- 11454870
TI  - A 32P-postlabeling assay for the oxidative DNA lesion 8,5'-cyclo-2'
      deoxyadenosine in mammalian tissues: evidence that four type II I-compounds are
      dinucleotides containing the lesion in the 3' nucleotide.
AB  - 8,5'-Cyclopurine-2'-deoxynucleotides, which are strong blocks to mammalian DNA
      and RNA polymerases, represent a novel class of oxidative DNA lesion in that they
      are specifically repaired by nucleotide excision repair but not by base excision
      repair or direct enzymatic reversion. Previous studies using thin layer
      chromatography of (32)P-postlabeled DNA digests have detected several bulky
      oxidative lesions of unknown structure, called I-compounds, in DNA from normal
      mammalian organs. We investigated whether any of these type II I-compounds
      contained 8,5'-cyclo-2'-deoxyadenosine (cA). Two previously detected type II I
      compounds were found to be dinucleotides of the sequence pAp-cAp and pCp-cAp.
      Furthermore, a modification of the technique resulted in detection of two
      additional I-compounds, pTp-cAp and pGp-cAp. Each I-compound isolated from
      neonatal rat liver DNA matched authentic (32)P-labeled cA-containing
      chromatographic standards under nine different chromatographic conditions. Their
      levels increased significantly after normal birth. The (32)P-postlabeling
      technique used here is capable of detecting 1-5 lesions/diploid mammalian cell.
      Thus, it should now be possible to detect changes of cA levels resulting from low
      level ionizing radiation and other conditions associated with oxidative stress,
      and to assess cA levels in tissues from patients with the genetic disease
      xeroderma pigmentosum who are unable to carry out nucleotide excision repair.

PMID- 11454871
TI  - DNA structure-specific nuclease activities in the Saccharomyces cerevisiae
      Rad50*Mre11 complex.
AB  - Saccharomyces cerevisiae RAD50 and MRE11 genes are required for the nucleolytic
      processing of DNA double-strand breaks. We have overexpressed Rad50 and Mre11 in
      yeast cells and purified them to near homogeneity. Consistent with the genetic
      data, we show that the purified Rad50 and Mre11 proteins form a stable complex.
      In the Rad50.Mre11 complex, the protein components exist in equimolar amounts.
      Mre11 has a 3' to 5' exonuclease activity that results in the release of
      mononucleotides. The addition of Rad50 does not significantly alter the
      exonucleolytic function of Mre11. Using homopolymeric oligonucleotide-based
      substrates, we show that the exonuclease activity of Mre11 and Rad50.Mre11 is
      enhanced for substrates with duplex DNA ends. We have examined the
      endonucleolytic function of Mre11 on defined, radiolabeled hairpin structures
      that also contain 3' and 5' single-stranded DNA overhangs. Mre11 is capable of
      cleaving hairpins and the 3' single-stranded DNA tail. These endonuclease
      activities of Mre11 are enhanced markedly by Rad50 but only in the presence of
      ATP. Based on these results, we speculate that the Mre11 nuclease complex may
      mediate the nucleolytic digestion of the 5' strand at secondary structures formed
      upon DNA strand separation.

PMID- 11454872
TI  - Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5
      HIV-1 infection through their antagonistic effects on CCR5.
AB  - Novel low molecular weight spirodiketopiperazine derivatives which potently
      inhibit R5 human immunodeficiency virus type 1 (HIV-1) infection through their
      antagonistic effects on CCR5 were identified. One such compound E913 (M(r) 484)
      specifically blocked the binding of macrophage inflammatory protein-1alpha (MIP
      1alpha) to CCR5 (IC(50) 0.002 microm) and MIP-1alpha-elicited cellular Ca(2+)
      mobilization (IC(50) approximately 0.02 microm). E913 potently inhibited the
      replication of laboratory and primary R5 HIV-1 strains as well as various
      multidrug-resistant monocyte/macrophage tropic (R5) HIV-1 at IC(50) values of
      0.03 to 0.06 microm. E913 was inactive against T cell tropic (X4) HIV-1; however,
      when combined with a CXCR4 antagonist AMD-3100, E913 potently and synergistically
      inhibited the replication of dualtropic HIV-1 and a 50:50 mixture of R5 and X4
      HIV-1. Antagonism in anti-HIV-1 activity was not seen when E913 was combined with
      the reverse transcriptase inhibitor zidovudine or protease inhibitors. E913
      proved to compete with the binding of antibodies to CCR5 which recognize the C
      terminal half of the second extracellular loop (ECL2B) of CCR5. E913 and its
      analogs are acid-resistant and orally bioavailable in rodents. These data warrant
      that spirodiketopiperazine derivatives be further developed as potential
      therapeutics for HIV-1 infection.

PMID- 11454873
TI  - TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction
      of cell death upon overexpression.
AB  - Tankyrase (TANK1) is a human telomere-associated poly(ADP-ribose) polymerase
      (PARP) that binds the telomere-binding protein TRF1 and increases telomere length
      when overexpressed. Here we report characterization of a second human tankyrase,
      tankyrase 2 (TANK2), which can also interact with TRF1 but has properties
      distinct from those of TANK1. TANK2 is encoded by a 66-kilobase pair gene (TNKS2)
      containing 28 exons, which express a 6.7-kilobase pair mRNA and a 1166-amino acid
      protein. The protein shares 85% amino acid identity with TANK1 in the ankyrin
      repeat, sterile alpha-motif, and PARP catalytic domains but has a unique N
      terminal domain, which is conserved in the murine TNKS2 gene. TANK2 interacted
      with TRF1 in yeast and in vitro and localized predominantly to a perinuclear
      region, similar to the properties of TANK1. In contrast to TANK1, however, TANK2
      caused rapid cell death when highly overexpressed. TANK2-induced death featured
      loss of mitochondrial membrane potential, but not PARP1 cleavage, suggesting that
      TANK2 kills cells by necrosis. The cell death was prevented by the PARP inhibitor
      3-aminobenzamide. In vivo, TANK2 may differ from TANK1 in its intrinsic or
      regulated PARP activity or its substrate specificity.

PMID- 11454874
TI  - Normal ligand binding and signaling by CD47 (integrin-associated protein)
      requires a long range disulfide bond between the extracellular and membrane
      spanning domains.
AB  - CD47 is a unique member of the Ig superfamily with a single extracellular Ig
      domain followed by a multiply membrane-spanning (MMS) domain with five
      transmembrane segments, implicated in both integrin-dependent and -independent
      signaling cascades. Essentially all functions of CD47 require both the Ig and MMS
      domains, raising the possibility that interaction between the two domains is
      required for normal function. Conservation of Cys residues among CD47 homologues
      suggested the existence of a disulfide bond between the Ig and MMS domains that
      was confirmed by chemical digestion and mapped to Cys(33) and Cys(263). Subtle
      changes in CD47 conformation in the absence of the disulfide were suggested by
      decreased binding of two anti-Ig domain monoclonal antibodies, decreased
      SIRPalpha1 binding, and reduced CD47/SIRPalpha1-mediated cell adhesion.
      Mutagenesis to prevent formation of this disulfide completely disrupted CD47
      signaling independent of effects on ligand binding, as assessed by T cell
      interleukin-2 secretion and Ca(2+) responses. Loss of the disulfide did not
      affect membrane raft localization of CD47 or its association with alpha(v)beta(3)
      integrin. Thus, a disulfide bond between the Ig and MMS domains of CD47 is
      required for normal ligand binding and signal transduction.

PMID- 11454875
TI  - MEK6 regulates human involucrin gene expression via a p38alpha - and p38delta 
      dependent mechanism.
AB  - A signaling cascade that includes protein kinase C (PKC), Ras, and MEKK1
      regulates involucrin (hINV) gene expression in epidermal keratinocytes (Efimova,
      T., LaCelle, P., Welter, J. F., and Eckert, R. L. (1998) J. Biol. Chem. 273,
      24387-24395 and Efimova, T., and Eckert, R. L. (2000) J. Biol. Chem. 275, 1601
      1607). Because signal transfer downstream of MEKK1 may involve several MAPK
      kinases (MEKs), it is important to evaluate the regulatory role of each MEK
      isoform. In the present study we evaluate the role of MEK6 in transmitting this
      signal. Constitutively active MEK6 (caMEK6) increases hINV promoter activity and
      increases endogenous hINV levels. The caMEK6-dependent increase in gene
      expression is inhibited by the p38 MAPK inhibitor, SB203580, and is associated
      with a marked increase in p38alpha MAPK activity; JNK and ERK kinases are not
      activated. In addition, hINV gene expression is inhibited by dominant-negative
      p38alpha and increased when caMEK6 and p38alpha are co-expressed. caMEK6 also
      activates p38delta, but p38delta inhibits the caMEK6-dependent activation. These
      results suggest that MEK6 increases hINV gene expression by regulating the
      balance between activation of p38alpha, which increases gene expression, and
      p38delta, which decreases gene expression.

PMID- 11454876
TI  - Menopause and breast cancer: addressing the secondary health effects of adjuvant
      chemotherapy.

PMID- 11454877
TI  - Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in
      women with early-stage breast cancer.
AB  - PURPOSE: We sought to evaluate the effects of chemotherapy-induced ovarian
      failure on bone loss and markers of skeletal turnover in a prospective
      longitudinal study of young women with breast cancer receiving adjuvant
      chemotherapy. PATIENTS AND METHODS: Forty-nine premenopausal women with stage
      I/II breast cancers receiving adjuvant chemotherapy were evaluated within 4 weeks
      of starting chemotherapy (baseline), and 6 and 12 months after starting
      chemotherapy with dual-energy absorptiometry and markers of skeletal turnover
      osteocalcin and bone-specific alkaline phosphatase. Chemotherapy-induced ovarian
      failure was defined as a negative pregnancy test, greater than 3 months of
      amenorrhea, and a follicle-stimulating hormone > or = 30 MIU/mL at the 12-month
      evaluation. RESULTS: Among the 35 women who were defined as having ovarian
      failure, highly significant bone loss was observed in the lumbar spine by 6
      months and increased further at 12 months. The median percentage decrease of bone
      mineral density in the spine from 0 to 6 months and 6 to 12 months was -4.0
      (range, -10.4 to +1.0; P =.0001) and -3.7 (range, -10.1 to 9.2; P =.0001),
      respectively. In contrast, there were no significant decreases in bone mineral
      density in the 14 patients who retained ovarian function. Serum osteocalcin and
      bone specific alkaline phosphatase, markers of skeletal turnover, increased
      significantly in the women who developed ovarian failure. CONCLUSION:
      Chemotherapy-induced ovarian failure causes rapid and highly significant bone
      loss in the spine. This may have implications for long-term breast cancer
      survivors who may be at higher risk for osteopenia, and subsequently
      osteoporosis. Women with breast cancer who develop chemotherapy-induced ovarian
      failure should have their bone density monitored and treatments to attenuate bone
      loss should be evaluated.

PMID- 11454878
TI  - Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated
      liposomal doxorubicin versus topotecan.
AB  - PURPOSE: To compare the efficacy and safety of pegylated liposomal doxorubicin
      (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred
      after or didn't respond to first-line, platinum-based chemotherapy. PATIENTS AND
      METHODS: Patients with measurable and assessable disease were randomized to
      receive either PLD 50 mg/m(2) as a 1-hour infusion every 4 weeks or topotecan 1.5
      mg/m(2)/d for 5 consecutive days every 3 weeks. Patients were stratified
      prospectively for platinum sensitivity and for the presence or absence of bulky
      disease. RESULTS: A total of 474 patients were treated (239 PLD and 235
      topotecan). They comprised the intent-to-treat population. The overall
      progression-free survival rates were similar between the two arms (P =.095). The
      overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively
      (P =.390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for
      topotecan. Data analyzed in platinum-sensitive patients demonstrated a
      statistically significant benefit from PLD for progression-free survival (P
      =.037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall
      survival, PLD was significantly superior to topotecan (P =.008), with a median of
      108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a
      nonstatistically significant survival trend in favor of topotecan (P =.455).
      Severe hematologic toxicity was more common with topotecan and was more likely to
      be associated with dosage modification, or growth factor or blood product
      utilization. CONCLUSION: The comparable efficacy, favorable safety profile, and
      convenient dosing support the role of PLD as a valuable treatment option in this
      patient population.

PMID- 11454879
TI  - Variation in delivery of palliative radiotherapy to persons dying of cancer in
      nova scotia, 1994 to 1998.
AB  - PURPOSE: To examine sociodemographic and clinical variables associated with
      provision of palliative radiotherapy (RT) to persons dying of cancer. METHODS:
      The Nova Scotia Cancer Registry was used to identify 9,978 adults who were dying
      of cancer between 1994 and 1998 in the Canadian province of Nova Scotia. RT
      records from between April 1992 and December 1998 were obtained from the
      provincial treatment database. Multivariate analysis identified factors
      associated with two sequential decisions determining provision of palliative RT
      in the last 9 months of life: likelihood of receiving an RT consultation with a
      radiation oncologist and, given a consultation, likelihood of being treated with
      palliative RT. RESULTS: The likelihood of having a consultation decreased with
      age (20 to 59 years v. 80+ years: odds ratio [OR], 4.43 [95% confidence interval,
      3.80 to 5.15]), increased with community median household income (> $50,000 v. <
      $20,000: OR, 1.31 [1.02 to 1.70]), was higher for residents closer to the cancer
      center (< 25 km v 200+ km: OR, 2.47 [2.16 to 2.83]), increased between 1994 and
      1998 (OR, 1.34 [1.16 to 1.56]), varied by cause of death (relative to thoracic
      cancers, head and neck: OR, 1.75 [1.31 to 2.33]; gynecologic: OR, 0.35 [0.27 to
      0.44]), and was greater for those who had prior RT (OR, 2.20 [1.89 to 2.56]).
      Similar associations were observed when outcome was the provision of palliative
      RT given a consult, with one notable exception: prior RT was associated with a
      lower likelihood of receiving palliative RT (OR, 0.48 [0.40 to 0.58]).
      CONCLUSION: Variations observed in delivery of palliative RT should prompt
      further investigation into equity of access to clinically appropriate, palliative
      radiation consultation and treatment.

PMID- 11454880
TI  - High-dose intra-arterial cisplatin boost with hyperfractionated radiation therapy
      for advanced squamous cell carcinoma of the head and neck.
AB  - PURPOSE: To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin
      boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced
      squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Forty
      two patients with locally advanced primary SCCHN were treated on consecutive
      phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2
      Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT
      boost treatment). RESULTS: Acute grade 3 to 4 toxicities were as follows: grade 4
      and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%),
      respectively, and grade 3 hematologic, infectious, and skin events occurred in
      one patient each. Eight of 24 patients (33%) were unable to receive a second
      planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or
      emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1).
      Thirty-seven patients (88%) experienced complete response (CR) at primary site.
      Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR.
      The actuarial 2-year rates of locoregional control and disease-specific and
      overall survival are 73%, 63%, and 57%, respectively, with a median active follow
      up of 30 months. CONCLUSION: In this highly unfavorable subset of patients, these
      results seem superior to previously reported chemoradiation regimens in more
      favorable patients. Use of a second dose of IA cisplatin boost was associated
      with increased toxicity without obvious therapeutic gain. This novel strategy
      allows for an incremental increase in the treatment intensity of the HFX-RT
      regimen recently established as superior to once-a-day RT.

PMID- 11454881
TI  - Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative
      preparative regimens: impact of pretransplantation and posttransplantation
      factors on outcome.
AB  - PURPOSE: To analyze the impact of pre- and posttransplantation factors on the
      outcome of allogeneic transplantation after nonmyeloablative conditioning
      regimens. PATIENTS AND METHODS: Ninety-two allogeneic transplantations after
      nonmyeloablative preparative regimens were reported to the Societe Francaise de
      Greffe de Moelle Registry registry. Initial diagnoses were lymphoid diseases (n =
      22), myeloma (n = 14), acute leukemia and myelodysplasia (n = 41), chronic
      myelogenous leukemia (n = 12), and solid tumors (n = 3). Forty-six patients had
      previously received a transplant, and 49 had progressive disease before
      transplantation. Three types of conditioning regimens were used with fludarabine
      or antithymocyte globulins. Eighty-nine patients underwent transplantation, 60
      from peripheral-blood progenitor cells. Eighty-six patients received graft-versus
      host disease (GHVD) prophylaxis for a median duration of 53 days. RESULTS:
      Seventy-nine patients engrafted, with 40 complete and 21 mixed chimerisms. The
      acute GHVD rate at 3 months was 50% +/- 11%. Fifty-two patients achieved complete
      remission and 12, partial remission. At 18 months after transplantation, the
      overall survival (OS) and the transplant-related mortality (TRM) were 32% +/- 12%
      and 38% +/- 14%, respectively. Initial diagnosis and disease status before
      transplantation significantly influenced survival. Age and GHVD prophylaxis type
      significantly influenced TRM. We also showed an impact of GHVD prophylaxis
      duration on OS and TRM. In multivariate analysis, three factors remained of
      prognostic value on OS: initial diagnosis, disease status at transplantation, and
      GHVD prophylaxis duration. CONCLUSION: This series shows encouraging results from
      nonmyeloablative conditioning regimens before allotransplantation and
      demonstrates the impact of some pre- and posttransplantation factors on outcome
      after transplantation.

PMID- 11454882
TI  - Eligibility for hematopoietic stem-cell transplantation for primary systemic
      amyloidosis is a favorable prognostic factor for survival.
AB  - PURPOSE: Based on the success of hematopoietic stem-cell transplantation (HSCT)
      for multiple myeloma, HSCT is being used to treat patients with primary systemic
      amyloidosis (AL). This article addresses the extent to which eligibility to
      undergo HSCT is a favorable prognostic feature and explores prognostic factors
      within the subset of eligible patients. PATIENTS AND METHODS: The Mayo Clinic
      amyloid database was queried for all patients with AL seen at the Mayo Clinic
      from 1983 through 1997 who would have been eligible for peripheral-blood stem
      cell transplantation. Inclusion criteria included biopsy-proven amyloid,
      symptomatic disease, absence of a clinical diagnosis of multiple myeloma, age <
      or = 70 years, cardiac interventricular septal thickness < or = 15 mm, cardiac
      ejection fraction more than 55%, serum creatinine < or = 2 mg/dL, and direct
      bilirubin < or = 2.0 mg/dL. RESULTS: Median age was 56 years (range, 25 to 70)
      with 79 (34%) older than 60 years. One hundred patients had early cardiac
      involvement; 41, hepatic involvement; 167, renal involvement; and 39, nerve
      involvement. The 229 patients have had a median follow-up of 52 months, and 151
      have died. The median survival was 42 months with 5- and 10-year survival rates
      of 36% and 15%, respectively. Important predictors of survival were size of M
      component in 24-hour urine, number of involved organs, alkaline phosphatase,
      performance score, and weight loss. CONCLUSION: The same patients who are
      eligible for HSCT are a good-risk population who do relatively well with
      chemotherapy (median survival, 42 months), substantially better than the expected
      median survival of 18 months for all patients with AL. A randomized trial is
      needed to assess the true effect of HSCT.

PMID- 11454883
TI  - Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase
      inhibitor, for advanced breast cancer versus megestrol acetate.
AB  - PURPOSE: To compare two doses of letrozole (0.5 mg and 2.5 mg every day) and
      megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal women with
      advanced breast cancer previously treated with antiestrogens. PATIENTS AND
      METHODS: This double-blind, randomized, multicenter, multinational study enrolled
      602 patients, all of whom were included in the primary analysis in the protocol.
      Patients had advanced or metastatic breast cancer with evidence of disease
      progression while receiving continuous adjuvant antiestrogen therapy, had
      experienced relapse within 12 months of stopping adjuvant antiestrogen therapy
      given for at least 6 months, or had experienced disease progression while
      receiving antiestrogen therapy for advanced disease. Tumors were required to be
      estrogen receptor- and/or progesterone receptor-positive or of unknown status.
      Confirmed objective response rate was the primary efficacy variable. Karnofsky
      Performance Status and European Organization for Research and Treatment of Cancer
      quality-of-life assessments were collected for 1 year. RESULTS: There were no
      statistically significant differences among the three treatment groups for
      overall objective tumor response. Patients treated with letrozole 0.5 mg had
      improvements in disease progression (P =.044) and a decreased risk of treatment
      failure (P =.018), compared with patients treated with megestrol acetate.
      Letrozole 0.5 mg showed a trend (P =.053) for survival benefit when compared with
      megestrol acetate. Megestrol acetate was more likely to produce weight gain,
      dyspnea, and vaginal bleeding, and the letrozole groups were more likely to
      experience headache, hair thinning, and diarrhea. CONCLUSION: Given a favorable
      tolerability profile, once-daily dosing, and evidence of clinically relevant
      benefit, letrozole is equivalent to megestrol acetate and should be considered
      for use as an alternative treatment of advanced breast cancer in postmenopausal
      women after treatment failure with antiestrogens.

PMID- 11454884
TI  - Phase II study of sequential administration of docetaxel followed by doxorubicin
      and cyclophosphamide as first-line chemotherapy in metastatic breast cancer.
AB  - PURPOSE: To evaluate the feasibility and efficacy of a sequential administration
      of four cycles of docetaxel (100 mg/m(2) every 3 weeks) followed by four cycles
      of doxorubicin and cyclophosphamide (AC; 60/600 mg/m(2) every 3 weeks), with
      subsequent consolidation with docetaxel or AC, as first-line chemotherapy in
      patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-eight
      patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1
      to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%)
      were given. Consolidation therapy was given to 33 patients (29 with docetaxel).
      RESULTS: Grade 4 neutropenia was the most frequent toxicity (83% of patients).
      This was not cumulative and was rarely complicated by febrile neutropenia or
      severe infection. The nonhematologic safety profile was favorable: there were no
      grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific
      toxicities were generally not severe. With a median cumulative doxorubicin dose
      of 397 mg/m(2) (range, 150 to 543 mg/m(2)), two incidences of unrelated
      congestive heart failure after further treatment with anthracyclines and two of
      asymptomatic left ventricular ejection fraction decrease were observed. Among the
      42 assessable patients, five (12%) had complete and 25 (60%) had partial
      responses, for an overall response rate of 71% (95% confidence interval, 55% to
      84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and
      median time to progression was 46 weeks (range, 3 of 72 weeks). With a median
      follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months).
      CONCLUSION: This docetaxel-based sequential schedule is safe and effective in
      first-line therapy for MBC, without incurring cumulative toxicity, and provides a
      feasible chemotherapeutic option in this clinical setting.

PMID- 11454885
TI  - Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in
      predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer
      patients.
AB  - PURPOSE: Few studies have examined the possible importance of biologic prognostic
      factors in breast cancer connected with differentiation and growth in predicting
      response to a specific adjuvant treatment. HER2, epidermal growth factor receptor
      (EGFR), and p53 have all been suggested as possible markers of tamoxifen
      resistance. The aim of this study was to investigate interactions between
      adjuvant treatment with tamoxifen and the content of EGFR, HER2, and p53 in
      steroid receptor-positive patients. PATIENTS AND METHODS: A total of 1,716 high
      risk postmenopausal breast cancer patients were randomly assigned to treatment
      with tamoxifen (868 women) or to observation (848 women) in a prospective trial
      (Danish Breast Cancer Cooperative Group's 77c protocol). The content of the
      steroid receptors and expression of p53, EGFR, and HER2 were determined by
      immunohistochemical analysis of paraffin-embedded tissue. The length of follow-up
      was 10 years. The end point for this analysis was disease-free survival. RESULTS:
      Multivariate analysis demonstrated no increased risk of recurrence after
      treatment with tamoxifen for HER2-, EGFR-, and p53-positive, high-risk, steroid
      receptor-positive patients. Patients with steroid receptor-positive tumors and
      positive immunohistochemical staining for HER2, EGFR or p53 benefited from
      treatment with tamoxifen for 1 year, although the latter variable contained
      independent prognostic information by itself. CONCLUSION: With the statistical
      power of the present randomized study, we did not find support for the hypothesis
      that HER2/EGFR or p53 status predicts benefit from tamoxifen treatment in
      estrogen receptor-positive patients with early-stage breast cancer. Thus, neither
      HER2, EGFR, nor p53 overexpression/accumulation should be used as a
      contraindication for giving tamoxifen.

PMID- 11454886
TI  - Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United
      States sample of cancer survivors.
AB  - PURPOSE: To evaluate the proposed cancer-related fatigue (CRF) diagnostic
      criteria in a sample of cancer survivors. More accurate prevalence estimates of
      CRF may result in improved diagnosis and management of one of the most common
      symptoms associated with cancer and its treatment. METHODS: Three hundred seventy
      nine individuals who had been treated with chemotherapy, either alone or in
      combination with radiation therapy, were surveyed. Patients were asked background
      questions about their current condition, their medical history, and the frequency
      of fatigue during their chemotherapy. Additionally, patients who reported
      experiencing fatigue at least a few days each month during treatment were asked a
      series of questions about the impact of fatigue on their daily functioning.
      RESULTS: One hundred forty-one (37%) individuals reported at least 2 weeks of
      fatigue in the previous month. Of the respondents who had received their last
      treatment more than 5 years ago, 33% still reported at least a 2-week period of
      fatigue in the month before the interview. Evaluation of the proposed criteria
      revealed that 17% of respondents met at least two criteria for CRF. CONCLUSION:
      The prevalence of diagnosable CRF in the individuals in this sample, most of whom
      had completed treatment more than 1 year ago, was 17%-lower than expected based
      on previous reports that have used less-strict criteria. In a sizable number of
      people, CRF persists well beyond active treatment and should be a focus of
      intervention. Although they will require replication in other samples and
      clinical validation, these formal diagnostic criteria can be a step toward common
      language and a better understanding of the severity range and persistence of CRF.

PMID- 11454887
TI  - Funding new cancer drugs in Ontario: closing the loop in the practice guidelines
      development cycle.
AB  - PURPOSE: The previously described practice guidelines development cycle follows
      an iterative model in which recommendations are reached by a process that
      incorporates practitioners at all phases. A key feature is the separation of the
      evidence-based systematic review and the generation of recommendations from
      policy decisions surrounding implementation. This article describes how this
      implementation phase has evolved in Ontario and how implementation has affected
      the guidelines process. METHODS: The development of the New Drug Funding Program
      in Ontario and the appointment of a policy advisory committee (PAC) to make
      funding recommendations were reviewed. The decision-making framework of the PAC
      is described in this article. RESULTS: The PAC has had to address a number of
      issues in making funding recommendations. These issues have included dealing with
      evidence arising solely from phase II versus phase III trials, using economic
      information, and involving community representatives in its deliberations. Its
      activities have had a substantial impact on the practice guidelines initiative.
      CONCLUSION: It is possible to integrate an evidence-based, practitioner-driven
      approach to clinical guideline development with a funding program that takes
      policy considerations into account. However, even though these two roles are
      conceptually separate, the needs of the funding program have inevitably had an
      impact on the guidelines process.

PMID- 11454888
TI  - Extending positron emission tomography scan utility to high-risk neuroblastoma:
      fluorine-18 fluorodeoxyglucose positron emission tomography as sole imaging
      modality in follow-up of patients.
AB  - PURPOSE: Although positron emission tomography (PET) with fluorine-18
      fluorodeoxyglucose ((18)F-FDG) has a major impact on the treatment of adult
      cancer, the reported experience with extracranial tumors of childhood is limited.
      We describe a role for PET in patients with neuroblastoma (NB). PATIENTS AND
      METHODS: In 51 patients with high-risk NB, 92 PET scans were part of a staging
      evaluation that included iodine-123 or iodine-131 metaiodobenzylguanidine (MIBG)
      scan, bone scan, computed tomography (and/or magnetic resonance imaging), urine
      catecholamine measurements, and bone marrow (BM) examinations. The minimum number
      of tests sufficient to detect NB was determined. RESULTS: Of 40 patients who were
      not in complete remission, only 1 (2.5%) had NB that would have been missed had a
      staging evaluation been limited to PET and BM studies, and 13 (32.5%) had NB
      detected by PET but not by BM and urine tests. PET was equal or superior to MIBG
      scans for identifying NB in soft tissue and extracranial skeletal structures, for
      revealing small lesions, and for delineating the extent and localizing sites of
      disease. In 36 evaluations of 22 patients with NB in soft tissue, PET failed to
      identify only two long-standing MIBG-negative abdominal masses. PET and MIBG
      scans showed more skeletal lesions than bone scans, but the normally high
      physiologic brain uptake of FDG blocked PET visualization of cranial vault
      lesions. Similar to MIBG, FDG skeletal uptake was diffusely increased with
      extensive or progressing BM disease but faint or absent with minimal or
      nonprogressing BM disease. CONCLUSION: In the absence or after resolution of
      cranial vault lesions, and once the primary tumor is resected, PET and BM tests
      suffice for monitoring NB patients at high risk for progressive disease in soft
      tissue and bone/BM.

PMID- 11454889
TI  - No disadvantage in outcome of using matched unrelated donors as compared with
      matched sibling donors for bone marrow transplantation in children with acute
      lymphoblastic leukemia in second remission.
AB  - PURPOSE: We evaluated the outcome of children with acute lymphoblastic leukemia
      (ALL) in second remission (2CR), comparing bone marrow transplantation (BMT)
      using either matched sibling donors or unrelated donors (URDs). PATIENTS AND
      METHODS: A total of 65 patients, aged 2 months to 20 years at BMT, with ALL in
      2CR underwent allogeneic BMT at seven Nordic centers during 1990 to 1997. Of the
      first relapses, 85% were in bone marrow; 46% occurred on therapy, and 54%, off
      therapy. The preparative regimens were cyclophosphamide plus total-body
      irradiation +/- antithymocyte/antilymphocyte globulin, busulfan plus
      cyclophosphamide +/- antithymocyte/antilymphocyte globulin, or cytarabine plus
      total-body irradiation. Of the allografts, 37 were from HLA-matched siblings and
      28 were from URDs. RESULTS: In the sibling versus URD graft recipient groups, the
      posttransplantation 5-year event-free survival was 39% versus 54% (P =.4), the
      estimated posttransplantation relapse rate was 76% versus 40% (P = not
      significant [NS]), and the toxic death rate was 19% versus 11% (P = NS). The
      incidence of significant (grade 2 to 4) acute graft-versus-host disease (GVHD)
      was 38% versus 64% (P <.05) and was 14% versus 32% (P <.10) for severe (grade 3
      to 4) acute GVHD; the incidence of chronic GVHD was 26% versus 57% (P <.05) and
      was 13% versus 22% (P = NS) for extensive chronic GVHD in the sibling and URD
      groups. CONCLUSION: BMT with matched URD allografts offers at least equal
      survival for children with ALL in 2CR, as compared with allografts from matched
      sibling donors. URD allografts were not associated with a higher toxic mortality
      rate, although both acute and chronic GVHD were more frequent with URD.
      Indications for using matched URD allografts in ALL 2CR can be considered the
      same as for using matched sibling donors.

PMID- 11454890
TI  - Prospective, multicenter evaluation of risk factors associated with invasive
      bacterial infection in children with cancer, neutropenia, and fever.
AB  - PURPOSE: To identify clinical and laboratory parameters present at the time of a
      first evaluation that could help predict which children with cancer, fever, and
      neutropenia were at high risk or low risk for an invasive bacterial infection.
      PATIENTS AND METHODS: Over a 17-month period, all children with cancer, fever,
      and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto
      a prospective protocol. Associations between admission parameters and risk for
      invasive bacterial infection were assessed by univariate and logistic regression
      analyses. RESULTS: A total of 447 febrile neutropenic episodes occurred in 257
      children. Five parameters were statistically independent risk factors for an
      invasive bacterial infection. Ranked by order of significance, they were as
      follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2;
      95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95%
      CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to
      2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to
      2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6).
      Other previously postulated risk factors (magnitude of fever, monocyte count)
      were not independent risk factors in this study population. CONCLUSION: In a
      large population of children, common clinical and laboratory admission parameters
      were identified that can help predict the risk for an invasive bacterial
      infection. These results encourage the possibility of a more selective management
      strategy for these children.

PMID- 11454891
TI  - Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer
      cells and its biologic effects: a phase I clinical trial.
AB  - PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A
      gene is associated with antitumor activities by transcriptional repression of HER
      2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce
      regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice.
      Therefore, we evaluated the feasibility of intracavitary injection of E1A gene
      complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER
      2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a
      phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A
      cationic liposome was injected once a week into the thoracic or peritoneal cavity
      of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12).
      RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical
      staining and reverse transcriptase-polymerase chain reaction. This E1A gene
      expression was accompanied by HER-2/neu downregulation, increased apoptosis, and
      reduced proliferation. The most common treatment-related toxicities were fever,
      nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These
      results argue for the feasibility of intracavitary DCC-E1A administration,
      provide a clear proof of preclinical concept, and warrant phase II trials to
      determine the antitumor activity of the E1A gene.

PMID- 11454892
TI  - Safety and efficacy of bisphosphonates beyond 24 months in cancer patients.
AB  - PURPOSE: Bisphosphonate therapy has decreased the risk of skeletal complications
      associated with osteolytic bone lesions in patients with breast cancer and
      multiple myeloma. The large prospective studies have used 21 to 24 months of
      treatment. We studied the safety and efficacy of bisphosphonates in a subset of
      patients who received therapy for more than 24 months. PATIENTS AND METHODS:
      Patients who received bisphosphonates (pamidronate or zoledronic acid) were
      identified. Data on skeletal events and laboratory parameters were gathered by
      chart review. RESULTS: We studied 22 patients who received intravenous
      pamidronate or zoledronic acid for a duration of 3.6 years (range, 2.2 to 6.0
      years). Prolonged therapy was well tolerated. No significant calcium, phosphorus,
      electrolyte, or WBC count abnormalities were encountered. There was a clinically
      insignificant decrease in hemoglobin and platelet count and an increase in
      creatinine in these patients. The fracture rate beyond 2 years was no greater
      than during the first 2 years of treatment. There were no stress fractures of
      long bones with prolonged therapy. CONCLUSION: Prolonged treatment with the
      potent bisphosphonates pamidronate and zoledronic acid seems to be well tolerated
      and should be studied in prospective, randomized studies to document prolonged
      skeletal efficacy.

PMID- 11454893
TI  - Changing patterns of symptom control and palliative care paper presentations at
      the annual meeting of the American Society of Clinical Oncology.

PMID- 11454894
TI  - Developing drugs to decrease the toxicity of chemotherapy.

PMID- 11454895
TI  - Efficacy and safety of a combined rituximab chemotherapy during pregnancy.

PMID- 11454896
TI  - Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide
      for metastatic breast cancer.

PMID- 11454897
TI  - Thymidylate synthase promoter polymorphism.

PMID- 11454899
TI  - Competitive neuronal nicotinic receptor antagonists: a new direction for drug
      discovery.
AB  - Neuronal nicotinic acetylcholine receptors are distributed extensively throughout
      the central and peripheral nervous systems. Currently, there is great interest in
      determining the structural and functional diversity of these receptors, and in
      developing subtype-selective agonists that have potential as therapeutic agents
      for neuropathology and disease. However, relatively little attention has been
      focused on the development of subtype-selective nicotinic receptor antagonists.
      Such antagonists would be beneficial for establishing the role of specific
      nicotinic receptor subtypes in physiological function and for unraveling the
      complexities of neuronal nicotinic receptor function. Furthermore, these subtype
      selective antagonists may also prove to be beneficial in the treatment of
      neuropathology and disease. The current perspective summarizes the research that
      has been carried out with both classical competitive antagonists and more
      recently developed competitive nicotinic receptor antagonists.

PMID- 11454900
TI  - Alpha1-adrenergic receptors: new insights and directions.
AB  - The adrenergic receptors play a key role in the modulation of sympathetic nervous
      system activity as well as a site of action for many therapeutic agents. The
      alpha1-adrenergic receptor subtypes (alpha1A-, alpha1B-, alpha1D) are the prime
      mediators of smooth muscle contraction and hypertrophic growth, but their
      characterization in both binding and function have lagged the other adrenergic
      family members. Although they are derived from a related ancestral gene and all
      nine adrenergic receptor family members bind the endogenous ligands, epinephrine
      and norepinephrine, with roughly similar affinities, there are major differences
      in the mode of binding, second messenger utilization, and physiological effects
      of the alpha1-subtypes compared with beta- or alpha2-subtypes. Here, we review
      the recent literature on aspects of its binding pocket and how it differs from
      the beta-adrenergic receptor paradigms. We also review the signaling components
      and aspects of its function and provide new insights into its roles in smooth
      muscle, growth, neurological, and cardiovascular function.

PMID- 11454901
TI  - Prevention of allergic inflammation by a novel prostaglandin receptor antagonist,
      S-5751.
AB  - Prostaglandin (PG) D2, the major cyclooxygenase metabolite generated from
      immunologically stimulated mast cells, is thought to contribute to the
      pathogenesis of allergic diseases due to its various inflammatory effects.
      However, since no DP receptor antagonist has been developed as an antiallergic
      drug, the role of PGD2 in the pathogenesis of allergic diseases remains
      uncertain. Here, we report the in vivo efficacy of our newly established DP
      receptor antagonist, S-5751 [((Z)-7-[(1R,2R,3S,5S)-2-(5-hydroxy benzo[b]thiophen
      3-ylcarbonylamino)-10-norpinan-3-yl]hept-5- enoic acid)], using various allergic
      inflammation guinea pig models. In allergic rhinitis models, oral administration
      of S-5751 dramatically inhibited not only early nasal responses, as assessed by
      sneezing, mucosal plasma exudation, and nasal blockage, but also late responses
      such as mucosal plasma exudation and eosinophil infiltration. Even when S-5751
      was administered after recovery from the early responses, these late phase
      responses were almost completely suppressed. In addition, S-5751 alleviated
      allergen-induced plasma exudation in the conjunctiva in an allergic
      conjunctivitis model and antigen-induced eosinophil infiltration into the lung in
      an asthma model. These findings provide evidence for the crucial role of PGD2 as
      a mediator of allergic inflammation in guinea pigs and suggest that DP receptor
      antagonists may be useful in the treatment of allergic diseases triggered by mast
      cell activation.

PMID- 11454902
TI  - Characterization of the NADPH-dependent metabolism of 17beta-estradiol to
      multiple metabolites by human liver microsomes and selectively expressed human
      cytochrome P450 3A4 and 3A5.
AB  - We characterized the NADPH-dependent metabolism of 17beta-estradiol (E2) by liver
      microsomes from 21 male and 12 female human subjects. A large number of
      radioactive estrogen metabolite peaks were detected following incubations of
      [3H]E2 with male or female human liver microsomes in the presence of NADPH. The
      structures of 18 hydroxylated or keto estrogen metabolites formed by these
      microsomes were identified by gas chromatography/mass spectrometry analysis. 2
      Hydroxylation (the formation of 2-OH-E2 and 2-OH-E1) was the dominant metabolic
      pathway with all human liver microsomes tested. The average ratio of 4-OH-E2 to 2
      OH-E2 formation was approximately 1:6. A new monohydroxylated E2 metabolite
      (chemical structure unidentified) was found to be one of the major metabolites
      formed by human liver microsomes of both genders. 6beta-OH-E2 and 16beta-OH-E2
      were also formed in significant quantities, but products of estrogen 16alpha
      hydroxylation (16alpha-OH-E2 + 16alpha-OH-E1) were quantitatively minor
      metabolites. In addition, many other estrogen metabolites such as 6-keto-E2,
      6alpha-OH-E2, 7alpha-OH-E2, 12beta-OH-E2, 15alpha-OH-E2, 15beta-OH-E2, 16beta-OH
      E1, and 16-keto-E2 were also formed in relatively small quantities. The overall
      profiles for the E2 metabolites formed by male and female human liver microsomes
      were similar, and their average rates were not significantly different. The
      activity of testosterone 6beta-hydroxylation (a selective probe for CYP3A4/5
      activity) strongly correlated with the rate of formation of 2-OH-E2, 4-OH-E2, and
      several other hydroxyestrogen metabolites by both male and female liver
      microsomes. The dominant role of hepatic CYP3A4 and CYP3A5 in the formation of
      these hydroxyestrogen metabolites was further confirmed by incubations of
      selectively expressed human CYP3A4 or CYP3A5 with [3H]E2 and NADPH.

PMID- 11454903
TI  - Adenosine-mediated mast cell degranulation in adenosine deaminase-deficient mice.
AB  - Adenosine is a signaling nucleoside that has been suggested to play a role in
      asthma in part through its ability to influence mediator release from mast cells.
      Adenosine levels are elevated in the lungs of asthmatics, further implicating
      this molecule in the regulation of lung inflammation and suggesting that animal
      models exhibiting endogenous increases in adenosine will be useful for the
      analysis of adenosine function. Adenosine deaminase (ADA) is a purine catabolic
      enzyme responsible for regulating the levels of adenosine in tissues and cells.
      ADA-deficient mice develop lung inflammation and damage reminiscent of that seen
      in asthma in association with elevated adenosine levels. In the current study, we
      investigated the status of mast cells in ADA-deficient lungs. ADA-deficient mice
      exhibited extensive lung mast cell degranulation concurrent with elevated
      adenosine levels. ADA enzyme therapy prevented the accumulation of lung adenosine
      as well as mast cell degranulation, suggesting that this process was dependent on
      elevated lung adenosine levels. Consistent with this, treatment of ADA-deficient
      mice with broad spectrum adenosine receptor antagonists attenuated degranulation
      by 30 to 40%, supporting the involvement of adenosine receptor signaling.
      Moreover, these studies demonstrate the ability of endogenously generated
      adenosine to influence lung mast cell degranulation in a receptor-mediated manner
      and establish ADA-deficient mice as a model system to investigate the specific
      adenosine receptor responses involved in the degranulation of lung mast cells.

PMID- 11454904
TI  - Expression of alpha-adrenoceptor subtypes by smooth muscle cells and adventitial
      fibroblasts in rat aorta and in cell culture.
AB  - Previous radioligand binding reports of vascular alpha-adrenoceptor (AR) density
      have been limited to total alpha1- or alpha2-ARs. Studies using whole blood
      vessel homogenates have not differentiated among receptor or mRNA expression by
      medial smooth muscle cells (SMCs) versus adventitial fibroblasts (AFBs).
      Therefore, we used quantitative reverse transcription-polymerase chain reaction
      and radioligand binding to measure alpha-AR subtypes in media, adventitia, and
      cultured SMCs and AFBs from rat aorta. Both media and adventitia expressed
      alpha1A-, alpha1B-, alpha1D-, and alpha2D-AR mRNAs, but in markedly different
      abundances. Total alpha1-AR density was the same for media and adventitia (Bmax =
      101 +/- 10 versus 96 +/- 16 fmol/mg of protein). However, densities for alpha1A-,
      alpha1B-, and alpha1D-AR subtypes in media were 19 +/- 2, 26 +/- 4, and 55 +/-
      2%, and in adventitia were 44 +/- 3, 37 +/- 5, and 19 +/- 2%. No alpha2B- or
      alpha2C-AR transcripts were detected in either layer or in cultured SMCs or AFBs.
      Total alpha1-AR densities in cultured SMCs and AFBs (Bmax = 111 +/- 4 and 48 +/-
      6 fmol/mg of protein, respectively) were similar to media and adventitia, with
      alpha1B- and alpha1D-AR transcript levels and receptors largely sustained.
      However, alpha1A- and alpha2D-AR expression in cultured SMCs and AFBs was
      strongly reduced, compared with media and adventitia, an effect not prevented by
      30 different culture conditions. Like SMCs, exposure of AFBs to norepinephrine
      induced protein synthesis and proliferation of AFBs. This is the first study to
      quantitate alpha-AR subtype expression in media and adventitia and in cultured
      SMCs and AFBs. In addition, we report the intriguing finding that AFBs express
      alpha1-ARs in similar abundance as medial SMCs and that norepinephrine induced
      them to proliferate.

PMID- 11454905
TI  - [3H]LY341495 binding to group II metabotropic glutamate receptors in rat brain.
AB  - [3H]LY341495 is a highly potent and selective antagonist for group II
      metabotropic glutamate (mGlu) receptors (mGlu2 and mGlu3), which has been used to
      label these receptors in cells expressing recombinant receptor subtypes. In this
      study, we characterized the kinetics, pharmacology, and distribution of
      [3H]LY341495 binding to mGlu receptors in rat brain tissue. Equilibrium
      experiments in the rat forebrain demonstrated binding to a single site that was
      saturable, reversible, and of high affinity (Bmax, 3.9 +/- 0.65 pmol/mg of
      protein, Kd, 0.84 +/- 0.11 nM). The relative order of potencies for displacement
      of [3H]LY341495 by mGlu receptor ligands was LY341495 >> L-glutamic acid >
      LY354740 > (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine > 4-(2R,4R)
      aminopyrrolidine-2,4-dicarboxylate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic
      acid > (R,S)-alpha-methyl-4-phosphonophenylglycine > (R,S)3,5
      dihydroxyphenylglycine > L-(+)-2-amino-4-phosphonobutyric acid. [3H]LY341495 was
      not displaced by the selective ionotropic glutamate receptor agonists N-methyl-D
      aspartic acid, (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, or
      kainate at concentrations up to 1 mM. Comparison of [3H]LY341495 binding in rat
      brain with recombinant mGlu receptor subtypes demonstrated a very high
      correlation with mGlu3 receptor binding (r2 = 0.957), a significant, but lower,
      correlation with mGlu2 receptor binding (r2 = 0.869), but no significant
      correlation to mGlu8 receptor binding (r2 = 0.284). Regional studies using
      autoradiography showed a similar distribution of [3H]LY341495 binding to that for
      group II mGlu receptors previously reported by others using immunocytochemical
      techniques. These studies indicate that [3H]LY341495 selectively labels group II
      (mGlu2/3) receptors, but under the conditions used, [3H]LY341495 may bind
      predominately to mGlu3 receptor populations in the rat forebrain.

PMID- 11454906
TI  - Metallothionein inhibits doxorubicin-induced mitochondrial cytochrome c release
      and caspase-3 activation in cardiomyocytes.
AB  - Previous studies using transgenic mice in which metallothionein (MT) was
      overexpressed only in the heart have demonstrated that MT protects from oxidative
      cardiac injury induced by doxorubicin (DOX), an important anticancer agent. MT
      cardioprotection is associated with its antiapoptotic effect. The present study
      was undertaken to test the hypothesis that MT suppresses DOX-induced apoptosis
      through inhibition of mitochondrial cytochrome c release and caspase-3
      activation. Primary cultures of cardiomyocytes isolated from the hearts of
      transgenic neonatal mice and nontransgenic controls were treated with DOX at a
      clinically relevant concentration (1.0 microM) for varying time periods.
      Apoptosis was detected in nontransgenic cardiomyocyte cultures by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Annexin V
      fluorescein isothiocyanate binding. This apoptotic effect was significantly
      suppressed in the MT-overexpressing transgenic cardiomyocytes. Western blot
      analysis revealed that DOX caused mitochondrial cytochrome c release.
      Furthermore, caspase-3 activation was observed. The activation of this apoptotic
      pathway by DOX was dramatically inhibited in the MT-overexpressing
      cardiomyocytes. To elucidate the role of reactive oxygen species (ROS) in the
      activation of the cytochrome c-mediated caspase-3 activation pathway, the
      intracellular levels of ROS and their localization were detected by fluorescent
      confocal microscopy. Mitochondrial ROS concentrations were dramatically elevated
      by DOX in nontransgenic cardiomyocytes. This elevation was completely inhibited
      almost in the MT-overexpressing cardiomyocytes. Thus, these results demonstrate
      that MT suppresses DOX-induced apoptosis in cardiomyocytes through, at least in
      part, inhibition of the cytochrome c-mediated apoptotic pathway.

PMID- 11454907
TI  - Attenuation of compensatory right ventricular hypertrophy and heart failure
      following monocrotaline-induced pulmonary vascular injury by the Na+-H+ exchange
      inhibitor cariporide.
AB  - Pulmonary hypertension results in compensatory right ventricular (RV)
      hypertrophy. We studied the role of the Na+-H+ exchange (NHE) in the latter
      process by determining the effect of the NHE-1 inhibitor cariporide after
      monocrotaline-induced pulmonary artery injury. Sprague-Dawley rats received a
      control or cariporide diet for 7 days, at which time they were administered
      either monocrotaline (60 mg/kg) or its vehicle. Twenty-one days later,
      monocrotaline control, but not cariporide-fed animals, demonstrated increased RV
      weights and cell size of 65 and 52%, respectively. Monocrotaline alone
      significantly increased RV systolic pressure and end diastolic pressure by 70 and
      94%, respectively, whereas corresponding values with cariporide were
      significantly reduced to 33 and 42%. Central venous pressure increased by 414% in
      control animals, which was significantly reduced by cariporide. Monocrotaline
      treatment produced a decrease in cardiac output of 28 and 8% in the absence or
      presence of cariporide (P < 0.05 between groups), respectively. Although body
      weights were significantly lower in both monocrotaline-treated groups compared
      with vehicle treatment, with cariporide the net gain in body weight was twice
      that seen in the monocrotaline-treated animals without cariporide. Monocrotaline
      also increased RV NHE-1 and atrial natriuretic peptide mRNA expression, which was
      abrogated by cariporide. Monocrotaline-induced myocardial necrosis, fibrosis, and
      mononuclear infiltration was completely prevented by cariporide. Cariporide had
      no effect on monocrotaline-induced pulmonary intimal wall thickening. Our results
      demonstrate that cariporide directly attenuates myocardial dysfunction after
      monocrotaline administration independent of pulmonary vascular effects. NHE-1
      inhibition may represent an effective adjunctive therapy that selectively targets
      myocardial hypertrophic responses in pulmonary vascular injury.

PMID- 11454908
TI  - Tumor growth inhibition in vivo and G2/M cell cycle arrest induced by antisense
      oligodeoxynucleotide targeting thymidylate synthase.
AB  - Chemotherapeutic agents targeting thymidylate synthase (TS) are effective against
      human tumors. Efficacy is limited by drug resistance, often mediated by TS
      overexpression. Treatment of HeLa cells in vitro with an antisense
      oligodeoxynucleotide (ODN 83) targeting human TS mRNA reduces TS mRNA and protein
      levels, inhibits cell proliferation, and sensitizes cells to TS-targeting drugs
      (Ferguson et al., 1999). The present study investigates the mechanism by which
      ODN 83 inhibits cell proliferation and examines its antitumor efficacy in vivo.
      ODN 83 treatment did not induce apoptosis in HeLa cells in vitro but caused
      accumulation of cells at G2/M. In contrast, TS-targeting chemotherapeutics arrest
      at G1 or S. Antisense down-regulation reduced TS mRNA levels in human colon
      cancer (HT29) cells by 40% in vitro, resulted in G2/M arrest, and reduced
      proliferation without enhanced cell death. Growth of HT29 tumors in
      immunocompromised mice was significantly inhibited when antisense ODN 83
      treatment began promptly after tumor implantation and was accompanied by a 40%
      reduction in TS protein levels. Growth of tumors allowed to reach 400 mm3 prior
      to ODN administration was unaffected by antisense ODN 83. Radiolabeled ODNs were
      localized to the tumor periphery but evenly distributed in normal tissue. Thus,
      down-regulation of TS mRNA and protein by antisense ODN treatment exerts a novel
      G2/M cell cycle block without increasing cell death and inhibits HT29 tumor cell
      growth in vivo. Antisense ODN 83 may be an effective therapy for colon carcinoma,
      alone or in combination with TS-targeting cytotoxic drugs.

PMID- 11454909
TI  - Rebamipide inhibits ceramide-induced interleukin-8 production in Kato III human
      gastric cancer cells.
AB  - Helicobacter pylori adheres to gastric epithelial cells and stimulates
      interleukin-8 production. Ceramide, a lipid second messenger, has become known as
      an important mediator of some actions of several cytokines. We have recently
      reported that H. pylori-dependent ceramide production may activate nuclear factor
      kappaB and mediate interleukin-8 expression in human gastric cancer cell lines.
      In this study, we evaluated the effect of rebamipide, an antigastritis and
      antiulcer agent, on H. pylori-dependent ceramide production and subsequent
      interleukin-8 expression in Kato III cells. Rebamipide inhibited ceramide-induced
      interleukin-8 expression in a dose-dependent manner. Rebamipide decreased the
      ceramide-induced increase of the interleukin-8 mRNA level as assessed by Northern
      blotting. Rebamipide suppressed interleukin-8 gene transcription and nuclear
      factor-kappaB-dependent transcriptional activity as assessed by luciferase assay.
      Rebamipide inhibited the ceramide-induced degradation of IkappaB-alpha (a major
      cytoplasmic inhibitor of nuclear factor-kappaB), further supporting that
      rebamipide inhibits the activation of nuclear factor-kappaB. Rebamipide also
      inhibited the ceramide-dependent activation of mitogen-activated protein kinases.
      Furthermore, rebamipide significantly attenuated the H. pylori-dependent increase
      in the intracellular ceramide level. These results suggest a novel mechanism by
      which rebamipide may protect against the mucosal inflammation associated with H.
      pylori infection.

PMID- 11454910
TI  - ATP-sensitive K+ channels and cellular actions of morphine in periaqueductal gray
      slices of neonatal and adult rats.
AB  - ATP-sensitive K+ (K(ATP)) channels were reported to be involved in morphine
      analgesia in vivo. The present study, using patch-clamp technique in brain slices
      of neonatal (P12-P16) and adult rats, investigated cellular actions of K(ATP)
      channel ligands and their interactions with morphine in the ventrolateral
      periaqueductal gray (PAG), a crucial site for morphine analgesia. In neonatal PAG
      neurons, morphine depressed evoked inhibitory postsynaptic currents (IPSCs) in
      almost all tested neurons and elicited an inwardly rectifying K+ current in one
      third of tested neurons. Glibenclamide (1-10 microM), a K(ATP) channel blocker,
      did not affect the membrane current or synaptic current per se but also failed to
      affect the effects of morphine. No outward current was elicited upon using
      microelectrodes containing ATP-free internal solution. In adult neurons,
      morphine, at the concentration up to 300 microM, failed to activate K+ current in
      all 25 neurons tested but depressed IPSCs to a comparable extent as that in
      neonatal neurons. Glibenclamide also failed to alter the effect of morphine in
      adult neurons. The openers of K(ATP) channels, lemakalim (10-30 microM) and
      diazoxide (10-500 microM), unlike morphine, did not increase membrane currents in
      both neonatal and adult neurons. However, diazoxide induced a glibenclamide
      sensitive outward current in hippocampal CA1 neurons. It is concluded that K(ATP)
      channels display little functional role per se and might not be involved in
      effects of morphine in the ventrolateral PAG. The correlation between the
      insensitivity in K+ channel activation and the less antinociceptive response to
      morphine in adults was discussed.

PMID- 11454911
TI  - Preventive effect of lactacystin, a selective proteasome inhibitor, on ischemic
      acute renal failure in rats.
AB  - To elucidate the role of a proteasome-dependent proteolytic pathway in the
      pathogenesis of acute renal failure (ARF), we examined the effect of a selective
      proteasome inhibitor, lactacystin, on ARF induced by ischemia/reperfusion.
      Ischemic ARF was induced by clamping the left renal artery and vein for 45 min
      followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function
      in untreated ARF rats markedly decreased at 24 h after reperfusion.
      Intraperitoneal injection of lactacystin at a dose of 0.1 mg/kg before the
      occlusion tended to attenuate the deterioration of renal function. The higher
      dose of lactacystin (1 mg/kg) markedly attenuated the ischemia/reperfusion
      induced renal dysfunction. Histopathological examination of the kidney of
      untreated ARF rats revealed severe lesions, such as tubular necrosis,
      proteinaceous casts in tubuli, and medullary congestion, all of which were
      markedly suppressed by the higher dose of lactacystin. In addition, endothelin
      (ET)-1 content in the kidney after the ischemia/reperfusion was significantly
      increased, being the maximum level at 6 h after the reperfusion, and this
      elevation was abolished by the higher dose of lactacystin. These results indicate
      that lactacystin prevents the development of ischemia/reperfusion-induced ARF,
      and the effect is accompanied by suppression of the enhanced ET-1 production in
      the kidney, thereby suggesting that a proteasome-dependent proteolytic pathway
      has a crucial role in the pathogenesis of ischemic ARF, possibly through the
      enhancement of ET-1 production in postischemic kidneys.

PMID- 11454912
TI  - Stereoselective metabolism of cisapride and enantiomer-enantiomer interaction in
      human cytochrome P450 enzymes: major role of CYP3A.
AB  - Cisapride is a chiral molecule that is marketed as a racemate consisting of two
      optical isomers, but little is known about its stereoselective metabolism.
      Studies with (-)-, (+)-, and (+/-)-cisapride were undertaken in human liver
      microsomes (HLMs) and recombinant cytochrome P450s (P450s) to determine the
      stereoselective metabolism and enantiomer-enantiomer interaction. Each enantiomer
      and racemic cisapride were N-dealkylated to norcisapride (NORCIS) and
      hydroxylated to 3-fluoro-4-hydroxycisapride (3-F-4-OHCIS) and 4-fluoro-2
      hydroxycisapride (4-F-2-OHCIS). The kinetics for the formation of NORCIS from (-)
      cisapride (Km = 11.9 +/- 4.8 microM; Vmax = 203 +/- 167 pmol/min/mg of protein)
      or (+)-cisapride (Km = 18.5 +/- 4.7 microM; Vmax = 364 +/- 284 pmol/min/mg of
      protein) in HLMs exhibited simple Michaelis-Menten kinetics, while a sigmoidal
      model characterized those of 3-F-4-OHCIS and 4-F-2-OHCIS. In vitro, NORCIS
      appears to be the major metabolite of both enantiomers. NORCIS and 3-F-4-OHCIS
      were preferentially formed from (+)-cisapride rather than (-)-cisapride, but that
      of 4-F-2-OHCIS was the reverse, suggesting regio- and stereoselective metabolism.
      The formation rate of each metabolite from each enantiomer (20 microM) in 18 HLMs
      was highly variable (e.g., NORCIS, >35-fold) and correlated with the activity of
      CYP3A (r = 0.6-0.85; p < 0.05). Coincubation of troleandomycin (50 microM) with
      cisapride enantiomers (15 microM) in HLMs resulted in potent inhibition of NORCIS
      formation (by 75-80%), while other inhibitors showed negligible effect. Of 10
      recombinant human P450s tested, CYP3A4 catalyzed the formation of NORCIS, 3-F-4
      OHCIS, and 4-F-2-OHCIS from each enantiomer and racemic cisapride (15 microM)
      with the highest specific activity (Km values close to those in HLMs). We noted
      that the rate of racemic cisapride metabolism by HLMs and recombinant human
      CYP3A4 is slower compared with equimolar concentrations of each enantiomer. When
      incubated simultaneously in HLMs, the enantiomers inhibit each other's
      metabolism. In conclusion, our data demonstrate for the first time the
      stereoselective metabolism and enantiomer-enantiomer interaction of cisapride.
      Provided that the potency or the response of the enantiomers differ,
      understanding the factors that control their disposition as opposed to that of
      racemic cisapride may better predict adverse drug interactions and the resulting
      prokinetic efficacy and cardiac safety of cisapride.

PMID- 11454913
TI  - Potassium channels as targets for ethanol: studies of G-protein-coupled inwardly
      rectifying potassium channel 2 (GIRK2) null mutant mice.
AB  - G-Protein-coupled inwardly rectifying potassium channels (GIRKs) regulate
      synaptic transmission and neuronal firing rates. Selective enhancement of GIRK2
      function by intoxicating concentrations of ethanol was recently shown for
      recombinant homomeric and heteromeric channels. We proposed that specific
      behavioral actions of ethanol are due to activation of GIRK channels and that
      these behaviors would be reduced or eliminated in GIRK2 null mutant ("knockout")
      mice. Three behavioral effects of ethanol were absent in mutant mice as compared
      with wild-type littermates: stimulation of home cage (habituated) motor activity,
      anxiolytic action in elevated-plus maze test, and handling-induced convulsions
      (HIC) after an acute injection of ethanol. In contrast to these reductions of
      ethanol action, mutant mice displayed greater ethanol-stimulated activity in
      peripheral regions of an open field. There were no differences between mutant and
      wild-type mice for ethanol-induced sleep time, acute functional tolerance, or HIC
      following chronic matched consumption of a liquid diet. Ethanol preference and
      consumption were equal for wild-type and mutant mice using the standard two
      bottle choice test with alternation of the bottles. However, this test was
      complicated by the strong side preference of the mice. When ethanol was presented
      constantly in their favored location, the consumption of ethanol was
      substantially higher for mutant than for wild-type mice. In the absence of
      ethanol, GIRK2 knockout mice showed more motor activity, less anxiety, and higher
      HIC. These results provide evidence that GIRK2 channels mediate specific
      behaviors, including anxiety and convulsions, and may influence effects of
      ethanol on these behaviors.

PMID- 11454914
TI  - Contribution of nitric oxide and prostanoids to the cardiac electrophysiological
      and coronary vasomotor effects of diadenosine polyphosphates.
AB  - We investigated the hypothesis that the coronary vasomotor and cardiac
      electrophysiological effects of diadenosine polyphosphates (Ap(n)A) are mediated
      via release of nitric oxide and prostanoids. Transmembrane right ventricular
      action potentials, refractory periods, and coronary perfusion pressure were
      recorded from isolated, Langendorff-perfused guinea pig hearts studied under
      constant flow conditions. The effects of threshold (1 nM) and maximal (1 microM)
      concentrations of diadenosine triphosphate (Ap3A), tetraphosphate (Ap4A),
      pentaphosphate (Ap5A), and hexaphosphate (Ap6A) were studied in the presence of
      nitric oxide (NO) synthase inhibitors [L-NG-nitroarginine methyl ester, 300
      microM; or L-N5-(1-iminoethyl)ornithine, 30 microM] or cyclooxygenase inhibitors
      (indomethacin, 100 microM or meclofenamate, 10 microM). Inhibition of
      cyclooxygenase and NO synthase both prevented the increases in action potential
      duration and refractory periods seen in response to Ap(n)A. Cyclooxygenase
      inhibition altered the vasomotor effects of the Ap(n)A in a manner that was
      related to the structure of the Ap(n)A compound (the effects of Ap3A were
      attenuated and those of Ap4A and Ap5A were prevented, while those of Ap6A were
      not abolished.) Inhibition of NO synthase did not abolish the vasomotor
      responses. These results demonstrate the importance of nitric oxide and
      prostanoids in the cardiac responses to Ap(n)A and support the hypotheses that
      the coronary vasomotor responses to Ap(n)A are mediated via release of
      prostanoids, that this is related to the structure of the compound, and that the
      cardiac electrophysiological responses to Ap(n)A involve both nitric oxide and
      prostanoid release.

PMID- 11454915
TI  - Rewarding properties of methylphenidate: sensitization by prior exposure to the
      drug and effects of dopamine D1- and D2-receptor antagonists.
AB  - In drug addiction, a sensitization phenomenon has been postulated to play a
      critical role. The aim of our study was to evaluate whether sensitization occurs
      to the rewarding properties of methylphenidate, a psychostimulant drug known to
      possess abuse potential, as assessed with the biased conditioned place preference
      method in rats. In addition, since the brain dopaminergic system is considered to
      be important in drug-reward, the involvement of dopamine D1- and D2-receptors
      both in the rewarding properties of methylphenidate and in sensitization to these
      properties was assessed. Conditioning with methylphenidate at doses of 1.25 to 20
      mg/kg increased preference for the paired environment, whereas a dose of 0.31
      mg/kg was ineffective. However, following the 7-day sensitization treatment with
      methylphenidate (0.62-20 mg/kg), conditioning with a dose of 0.31 mg/kg resulted
      in an increased preference for the paired environment, i.e., the rewarding
      properties of methylphenidate appeared to be sensitized. Control experiments
      indicated that the enhancement of preference was not due to attenuation of
      sensitization treatment-induced withdrawal nor to tolerance to aversive
      properties of methylphenidate. When conditioned with methylphenidate, D1
      antagonist SCH 23390 but not D2-antagonist raclopride prevented place preference.
      However, when coadministered with methylphenidate during the sensitization
      treatment, both SCH 23390 and raclopride prevented the development of
      sensitization. These data indicate that the rewarding properties of
      methylphenidate are sensitized by prior exposure to the drug and that both D1-
      and D2-receptors, the latter of which possibly more specifically, appear to be
      involved in the development of this sensitization.

PMID- 11454916
TI  - Functional role of alpha-calcitonin gene-related peptide in the regulation of the
      cardiovascular system.
AB  - It remains unknown whether the extent of vasoactive response to exogenous
      calcitonin gene-related peptide (CGRP) varies among different regional vascular
      beds. It is also unclear whether endogenous CGRP plays a functional role in
      regulating basal vascular activity. To address these two issues, experiments were
      conducted in 27 anesthetized rats instrumented with a carotid flow probe and
      catheters in a jugular vein, left ventricle (LV), and femoral artery, and in 6
      conscious dogs, chronically instrumented with LV pressure gauge, aortic and
      atrial catheters, and ascending aortic, coronary, carotid, and renal flow probes.
      In both species, administration of human alpha-CGRP (0.1-0.5 microg/kg, i.v.)
      induced a dose-dependent peripheral vasodilation that was completely abolished by
      pretreatment with alpha-CGRP[8-37] (30 microg/kg/min, i.v.), a competitive
      antagonist of CGRP receptors. Regional blood flow measured by the radioactive
      microsphere technique in rats showed that the alpha-CGRP (0.3 microg/kg, i.v.)
      induced increase in blood flow was greater (p < 0.05) in the heart (+53 +/- 16%)
      than in the brain (+14 +/- 6%). In the presence of beta-adrenergic receptor
      blockade with propranolol, however, the increases in blood flow in these two
      vascular beds were identical. In conscious dogs, alpha-CGRP (0.3 microg/kg, i.v.)
      produced similar increases in coronary (+24 +/- 6%), carotid (+26 +/- 3%), and
      renal (+26 +/- 6%) blood flow, which were different from the patterns induced by
      other vasodilators; at an equivalent level of reduction in mean arterial pressure
      and total peripheral resistance, alpha-CGRP increased coronary and carotid blood
      flow significantly less (p < 0.05) than adenosine or nitroprusside. Unlike alpha
      CGRP, adenosine and nitroprusside, as expected, induced pronounced differential
      blood flow changes in these vascular beds. Neither systemic hemodynamics nor
      regional blood flow distribution was altered by the administration of a
      pharmacological blocking dose of alpha-CGRP[8-37] in the two species. Thus, we
      conclude that endogenous alpha-CGRP does not play an important role in
      cardiovascular regulation under normal, resting conditions, although exogenous
      alpha-CGRP induces a marked, comparable vasorelaxation in different regional
      vascular beds.

PMID- 11454917
TI  - Effects of TAK-637, a novel neurokinin-1 receptor antagonist, on colonic function
      in vivo.
AB  - Substance P (SP) is an important neurotransmitter that mediates various gut
      functions; however, its precise pathophysiological role remains unclear. In this
      study, we investigated the effect of SP on colonic function and the effect of TAK
      637 [(aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5
      (4-methylphenyl)-7H-[1,4]diazocino[2,1-g][1,7]naphthyridine-6,13-dione] a new
      neurokinin-1 (NK1) receptor antagonist, on colonic responses to SP or stress in
      Mongolian gerbils. SP and the selective NK1 agonist [pGlu6]SP6-11 significantly
      increased fecal pellet output. TAK-637 reduced [pGlu6]SP6-11-induced defecation,
      but did not significantly affect neurokinin A-, 5-hydroxytryptamine- or carbachol
      stimulated defecation. Oral TAK-637 decreased restraint stress-stimulated fecal
      pellet output with an ID50 value of 0.33 mg/kg. Ondansetron and atropine, but not
      the peripheral kappa-receptor agonist trimebutine, also reduced restraint stress
      stimulated defecation. TAK-637 inhibited the increase in fecal pellet output
      stimulated by intracerebroventricular injection of corticotropin-releasing
      factor, but did not affect the stress-induced increase in plasma
      adrenocorticotropic hormone levels. Denervation of the sensory neurons with
      capsaicin did not affect stress-stimulated defecation. These results suggest that
      NK1 receptors in the enteric plexus play an important role in stress-induced
      changes in colonic function, and that TAK-637 may be useful in the treatment of
      functional bowel diseases such as irritable bowel syndrome.

PMID- 11454918
TI  - S33005, a novel ligand at both serotonin and norepinephrine transporters: I.
      Receptor binding, electrophysiological, and neurochemical profile in comparison
      with venlafaxine, reboxetine, citalopram, and clomipramine.
AB  - S33005 displayed marked affinity for native, rat, and cloned human serotonin (5
      HT) transporters (SERT) and less pronounced affinity for norepinephrine (NE)
      transporters (NET), while its affinity at dopamine (DA) transporters and >50
      other sites was negligible. Reuptake of 5-HT and (less potently) NE into cerebral
      synaptosomes was inhibited by S33005, whereas DA reuptake was little affected. In
      vivo, S33005 prevented depletion of cerebral pools of 5-HT by
      parachloroamphetamine. Furthermore, it decreased electrical activity of raphe
      localized serotonergic neurones, an action abolished by the 5-HT1A antagonist
      WAY100,635. At higher doses, S33005 blocked firing of locus ceruleus-localized
      adrenergic neurones, an action abolished by the alpha2-adrenergic antagonist
      idazoxan. In contrast, S33005 did not inhibit ventrotegmental dopaminergic
      neurones. In frontal cortex of freely moving rats, S33005 dose dependently
      elevated dialysate levels of 5-HT, NE, and DA. In hippocampus, levels of 5-HT and
      NE were similarly elevated, while in nucleus accumbens and striatum, levels of 5
      HT were increased whereas DA was unaffected. Upon chronic (2 weeks)
      administration, basal levels of NE were elevated in frontal cortex and, therein,
      5-HT2A receptor density was decreased. Comparative studies with clinically used
      antidepressants showed that venlafaxine possessed a profile similar to S33005 but
      was less potent. Clomipramine likewise interacted with SERTs and NETs but also
      with several other receptors types, while citalopram and reboxetine were
      preferential ligands of SERTs and NETs, respectively. In conclusion, S33005
      interacts potently with SERTs and, less markedly, with NETs. It enhances
      extracellular levels of 5-HT and NE throughout corticolimbic structures and
      selectively elevates dialysis levels of DA in frontal cortex versus subcortical
      regions.

PMID- 11454919
TI  - S33005, a novel ligand at both serotonin and norepinephrine transporters: II.
      Behavioral profile in comparison with venlafaxine, reboxetine, citalopram, and
      clomipramine.
AB  - Reflecting its potent inhibition of serotonin (5-HT) reuptake (accompanying
      paper), S33005 blocked spontaneous tail-flicks induced by parachloroamphetamine
      in rats. This action was mimicked by the 5-HT reuptake inhibitor, citalopram, and
      the 5-HT/norepinephrine (NE) reuptake inhibitor, venlafaxine, whereas the
      preferential NE reuptake inhibitor, reboxetine, was inactive. Consistent with its
      less potent interaction with NE transporters, higher doses of S33005 attenuated
      induction of hypothermia by reserpine, an action mimicked by reboxetine and
      venlafaxine, whereas citalopram was ineffective. In mice, S33005 reduced
      immobility in forced-swim and tail-suspension procedures. It also inhibited
      marble-burying behavior and suppressed aggressive behavior between resident and
      intruder animals. In rats, S33005 generalized to a discriminative stimulus
      elicited by citalopram and attenuated hypnotic-sedative actions of the alpha2
      adrenoceptor agonist, S18616. For these parameters, S33005 was a more potent
      agent (median, 1.2 mg/kg, s.c.) than venlafaxine, citalopram, reboxetine, or the
      tricyclic agent, clomipramine. Even at markedly higher doses (40.0-80.0 mg/kg,
      s.c.), S33005 little affected motor behavior. S33005 (10.0 mg/kg, s.c.) also
      increased responses in a learned helplessness paradigm in rats, whereas
      venlafaxine was ineffective. Finally, in a rat chronic mild-stress model, S33005
      dose- (2.5-40.0 mg/kg) and time- (2-5 weeks) dependently enhanced sucrose
      consumption. Venlafaxine was likewise active in this procedure. In conclusion, in
      line with its inhibition of 5-HT and (less potently) NE reuptake, S33005 is
      active in a broad range of models suggestive of antidepressant activity. It
      exerts its actions more potently than venlafaxine and clomipramine, and its
      overall profile is distinct from those of citalopram and reboxetine.

PMID- 11454920
TI  - Differential antinociception induced by spinally administered endomorphin-1 and
      endomorphin-2 in the mouse.
AB  - We have previously demonstrated that the antinociception induced by either
      endomorphin-1 or endomorphin-2 given supraspinally is mediated by the stimulation
      of mu-opioid receptors. However, the antinociception induced by endomorphin-2
      given supraspinally contains additional components, which are mediated by the
      spinal release of dynorphin A (1-17) acting on kappa-opioid receptors and the
      spinal release of [Met5]enkephalin acting on delta2-opioid receptors in the
      spinal cord. The present studies were performed to determine whether there are
      any differential effects on the tail-flick inhibition induced by endomorphin-1
      and endomorphin-2 given intrathecally (i.t.) in mice. Endomorphin-1 or
      endomorphin-2 given i.t. inhibited the tail-flick response in a dose-dependent
      manner. The tail-flick inhibition induced by endomorphin-1 was blocked by i.t.
      pretreatment with mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen
      Thr-NH2 (CTOP), but not kappa-opioid receptor antagonist nor-binaltorphimine (nor
      BNI), delta1-opioid receptor antagonist 7-benzylidene naltrexamine (BNTX), or
      delta2-opioid receptor antagonist naltriben (NTB). In contrast, the tail-flick
      inhibition induced by endomorphin-2 given i.t. was blocked by i.t. pretreatment
      with CTOP or nor-BNI, but not BNTX or NTB. Intrathecal pretreatment with
      antiserum against dynorphin A (1-17), but not antiserum against [Met5]enkephalin,
      [Leu5]enkephalin, or beta-endorphin, blocked the tail-flick inhibition induced by
      i.t.-administered endomorphin-2. None of these antisera attenuated the i.t.
      administered endomorphin-1-induced tail-flick inhibition. It is concluded that
      the tail-flick inhibition induced by endomorphin-1 and endomorphin-2 given
      spinally is mediated by the stimulation of mu-opioid receptors. However, the tail
      flick inhibition induced by spinally injected endomorphin-2 contains an
      additional component, which is mediated by the spinal release of dynorphin A (1
      17) acting on kappa-opioid receptors in the spinal cord. We propose that there
      are at least two different subtypes of micro-opioid receptors for endomorphin-1
      and endomorphin-2 to produce antinociception in the spinal cord.

PMID- 11454921
TI  - Suppression of transient outward potassium currents in mouse ventricular myocytes
      by imidazole antimycotics and by glybenclamide.
AB  - The whole-cell patch-clamp technique was used in adult mouse ventricular myocytes
      at 22 degrees C to study the transient outward current (I(to)) and its
      sensitivity to the antimycotics miconazole and clotrimazole, as well as to
      glybenclamide. I(to) elicited by depolarizing steps from a holding potential of 
      80 mV consisted of a fast inactivating component and a slowly inactivating
      component. In the presence of miconazole (IC50 of approximately 8 microM) or
      clotrimazole, I(to) peak amplitude was reduced and its inactivation accelerated,
      due to a selective suppression of the slow component, without an effect on the
      fast component or on the noninactivating current. The effect did not reverse upon
      washout, was not induced by intracellular drug application, and occurred without
      a change of the steady-state inactivation. In the presence of glybenclamide I(to)
      peak amplitude was reduced and its inactivation accelerated. In contrast to the
      antimycotics, glybenclamide suppressed both the fast and the slow components
      (IC50 of approximately 50 microM), its effect was reversible, and was associated
      with a negative shift of the steady-state inactivation. These data demonstrate a
      pharmacological separation of I(to) components using antimycotic drugs but not
      glybenclamide.

PMID- 11454922
TI  - Factors affecting the accelerated blood clearance of polyethylene glycol
      liposomes upon repeated injection.
AB  - Previously, we showed that long-circulating polyethylene glycol (PEG)-liposomes
      are cleared rapidly from the circulation when injected repeatedly in the same
      animal. In this article, we describe the effects of PEG-coating, the circulation
      time, the lipid dose, and the presence of encapsulated doxorubicin on the
      pharmacokinetics upon repeated injection in rats. Furthermore, the role of liver
      and splenic macrophages was investigated. Liposomes without PEG-coating also
      showed the so-called "enhanced clearance effect": blood levels at 4 h post
      injection decreased from 62.8 +/- 13.7% of injected dose (%ID) after the first
      injection to 0.54 +/- 0.21%ID after the second injection. This decrease was
      independent of the circulation time of the first dose. Decreasing the first lipid
      dose of PEG-liposomes to 0.05 micromol/kg still led to enhanced clearance of a
      second dose of 5 micromol/kg. No changes in pharmacokinetics were observed when
      the second dose was 50 micromol/kg. When hepatosplenic macrophages were depleted,
      no enhanced clearance of repeated liposome injections was observed. A dose of
      doxorubicin containing PEG-liposomes (Doxil), injected 1 week after injection of
      empty PEG-liposomes, was cleared rapidly from the circulation in rats. Our
      results indicate that hepatosplenic macrophages play an essential role in the
      enhanced clearance effect and that the change in pharmacokinetic behavior upon
      repeated injection is a general characteristic of liposomes, unrelated to the
      presence of PEG. Therefore, these findings may have a considerable impact on the
      clinical application of liposomal formulations that are administered repeatedly.

PMID- 11454923
TI  - Effects of Ca2+ sensitizers on contraction, [Ca2+]i transient and myofilament
      Ca2+ sensitivity in diabetic rat myocardium: potential usefulness as inotropic
      agents.
AB  - The purpose of the present study was to investigate the effects of Ca2+
      sensitizers EMD 57033, MCI-154, and EGIS-9377 in cardiac preparations from
      streptozotocin-induced diabetic rats. In enzymatically dissociated ventricular
      myocytes loaded with the Ca2+ probe indo 1, these Ca2+ sensitizers caused an
      increase in cell shortening without a significant effect on the intracellular
      Ca2+ ([Ca2+]i) transient. The contractile responses were substantially similar in
      myocytes from diabetic and age-matched control rats. In contrast, the contractile
      and [Ca2+]i responses to pimobendan and isoproterenol were significantly less in
      diabetic myocytes. The Ca2+ sensitivity of tension in beta-escin-skinned
      trabeculae from diabetic hearts was not significantly different from that of
      controls. The effect of EMD 57033 on myofilament responsiveness to Ca2+ was
      identical in control and diabetic preparations. The slower time course of
      relaxation observed in diabetic papillary muscles was further prolonged in the
      presence of EMD 57033. However, the extent of the increase in relaxation produced
      by EMD 57033 did not differ between control and diabetic muscles, and the
      detrimental effect on resting tension was less pronounced in the two groups. In
      anesthetized rats, echocardiography showed that intra-duodenal administration of
      EMD 57033 increased left ventricular systolic function without affecting
      variables of diastolic filling in both groups. Taken together, the present
      results suggest that Ca2+ sensitizers, unlike conventional inotropic agents, have
      the potential to increase in force of contraction to the same extent in
      nondiabetic and diabetic myocardium, possibly without exaggerating extremely the
      impairment of diastolic function in diabetes.

PMID- 11454924
TI  - Beta2-adrenoceptor-mediated prejunctional facilitation and postjunctional
      inhibition of sympathetic neuroeffector transmission in the guinea pig vas
      deferens.
AB  - This study examines the role of prejunctional and postjunctional beta
      adrenoceptors in the modulation of sympathetic cotransmission in the guinea pig
      vas deferens. The prejunctional involvement of beta-adrenoceptors was evaluated
      by testing the effects of several agonists and antagonists on the nerve
      stimulation-evoked overflow of ATP and norepinephrine (NE) from the "in vitro"
      vas deferens. The nonsubtype-selective beta-adrenoceptor agonist isoproterenol
      and the beta2-subtype-selective agonist clenbuterol increased, to a similar
      degree, the overflow of ATP and NE, while the beta1-subtype-selective agonist
      xamoterol and the beta3-subtype-selective agonist BRL 37 344 had no effect.
      Pretreatment with ICI 118, 551, a beta2-subtype-selective antagonist, abolished
      the facilitation of cotransmitter release by isoproterenol and clenbuterol, while
      the beta1-subtype-selective antagonist atenolol had no effect. Activation of beta
      adrenoceptors by either isoproterenol or clenbuterol, but not by xamoterol and
      BRL 37 344, reduced the amplitude of contractions evoked by exogenously applied
      ATP. Pretreatment with propranolol or ICI 118, 551, but not atenolol, prevented
      these inhibitory effects. Isoproterenol in lower concentrations produced dose
      dependent reduction of the purinergic but not the adrenergic phase of nerve
      stimulation-induced contraction of the guinea pig vas deferens. When applied in
      concentrations greater than 1 microM, isoproterenol, but not clenbuterol,
      actually produced a concentration-dependent facilitation of contractions evoked
      by both nerve stimulation and exogenously applied ATP. Antagonists of alpha
      adrenoceptors blocked these facilitatory effects. Together, these results
      demonstrate that beta2-adrenoceptors can influence sympathetic neuroeffector
      transmission both prejunctionally, where they facilitate equally well the release
      of sympathetic cotransmitters and postjunctionally, where they inhibit smooth
      muscle contractions evoked by ATP.

PMID- 11454925
TI  - Mapping genes that regulate density of dopamine transporters and correlated
      behaviors in recombinant inbred mice.
AB  - Binding of 3beta-(4-iodophenyl) tropane-2beta-carboxylic acid methyl ester
      ([125I]RTI-55) to the dopamine transporter (DAT) in neostriatum from C57BL/6J,
      DBA/2J, and 21 BXD recombinant inbred (RI) mouse strains indicated highly
      significant strain differences in DAT density (Bmax) but no significant
      differences in affinity (Kd) for this radioligand. Strain mean Bmax values and
      the known genomic locations of 1390 marker loci were used to carry out a genome
      wide search for quantitative trait loci (QTLs), which are chromosomal sites
      containing genes that influence DAT expression. This search revealed an unusually
      large effect QTL on chromosome 19 in the region of the proopiomelanocortin
      pseudogene Pomc-ps1 (8-11 cM), homologous to regions of human chromosomes 9q21
      and 11q12-13. This QTL (logarithm of the odds 4.7, df = 1, p = 3 x 10(-6)) by
      conservative estimates accounts for just over half of the genetic variation in
      DAT binding site density. The QTL is not the DAT gene itself (Dat1, chromosome
      13), but a powerful modulator of DAT expression in neostriatum. Furthermore, DAT
      expression levels in 20 of the BXD RI strains and the chromosome 19 QTL were
      correlated with cocaine and methamphetamine-induced locomotor activation and
      thermic responses (hypo- or hyperthermia), but were not correlated with behaviors
      related to sensitization, reward, voluntary consumption, stereotypy, or seizures
      induced by these two psychostimulant drugs. The results suggest that there is a
      gene(s) on proximal chromosome 19 that strongly influences DAT expression in
      neostriatum and may influence psychostimulant-induced activity and thermal
      responses.

PMID- 11454926
TI  - Distinct pharmacology of 2-hydroxycarbazole-induced Ca2+ release in the sea
      urchin egg.
AB  - 2-hydroxycarbazole, a compound structurally related to the Ca2+-mobilizing marine
      toxin 9-methyl-7-bromoeudistomin, has recently been proposed to activate both
      type 1 and type 2 ryanodine receptors in skeletal and cardiac muscle,
      respectively. This study was undertaken to evaluate the activity of this compound
      in the sea urchin egg homogenate, a model system used to characterize
      intracellular Ca2+ mobilization mechanisms. 2-Hydroxycarbazole was found to
      potently release Ca2+ in a concentration-dependent manner via a specific
      mechanism displaying apparent desensitization. Use of selective inhibitors of the
      Ca2+-mobilizing messengers inositol 1,4,5-trisphosphate, cyclic adenosine
      diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate, as well as
      desensitization of homogenates to each of these molecules, failed to inhibit the
      response to 2-hydroxycarbazole. However, the response to 2-hydroxycarbazole was
      competitively antagonized by caffeine. Investigation of the Ca2+ stores accessed
      by 2-hydroxycarbazole revealed Ca2+ release from a thapsigargin-insensitive pool.
      Finally, 2-hydroxycarbazole failed to enhance [3H]ryanodine binding, suggesting
      the operation of a nonryanodine receptor mechanism. These results demonstrate
      that 2-hydroxycarbazole is acting to modulate a Ca2+ release mechanism with
      distinct pharmacological properties to those previously reported in the sea
      urchin egg.

PMID- 11454927
TI  - Use of dopamine-beta-hydroxylase-deficient mice to determine the role of
      norepinephrine in the mechanism of action of antidepressant drugs.
AB  - Norepinephrine (NE) is thought to play an important role in the pathophysiology
      of depression, and in the mechanism of action of antidepressant compounds.
      Previously, we created mice that are unable to synthesize NE and epinephrine due
      to targeted disruption of the dopamine-beta-hydroxylase gene (Dbh). To
      specifically test the role of NE in mediating behavioral changes elicited by
      antidepressants, these mice were examined in the forced swim test. There was no
      difference in baseline immobility scores in the forced swim test between Dbh(+/-)
      mice, which have normal levels of NE, and Dbh(-/-) mice. However, the Dbh(-/-)
      mice failed to demonstrate antidepressant-like behavioral effects following the
      administration of several classes of antidepressants. These included the NE
      reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor
      pargyline, and the atypical antidepressant bupropion. In addition, desipramine
      significantly reduced immobility in the Dbh(-/-) mice following pretreatment with
      the synthetic NE precursor L-threo-3,4-dihydroxyphenylserine, but not saline.
      Biochemical studies showed that there was no significant difference in the
      regional brain levels of NE transporter immunoreactivity or monoamine oxidase
      activity, the primary targets for most of the compounds examined. Taken together,
      these data show that the use of mice that lack endogenous NE may be an important
      strategy for unraveling the role of NE in tests sensitive to the effects of
      various psychotherapeutic agents.

PMID- 11454928
TI  - P-selectin antagonism with recombinant p-selectin glycoprotein ligand-1 (rPSGL
      Ig) inhibits circulating activated platelet binding to neutrophils induced by
      damaged arterial surfaces.
AB  - Neutrophil P-selectin glycoprotein ligand-1 (PSGL-1) mediates the initial rolling
      and adhesion of neutrophils to P-selectin on activated endothelium and platelets.
      Platelet-neutrophil activation and binding occur in the blood of patients with
      arterial diseases, suggesting that arterial damage leads to these phenomena. We
      investigated the influence of endothelial surface integrity on circulating
      platelet activation and binding to neutrophils and the mechanism involved in
      these interactions. Expression of P-selectin on human platelets and their binding
      to neutrophils was determined by flow cytometry at baseline after thrombin
      activation and after exposure for 15 min to intact and damaged arterial surfaces
      in flow chambers. Expression of platelet P-selectin at baseline and after
      perfusion over intact endothelium averaged 13.8 +/- 1.2 and 12.7 +/- 1.8%,
      respectively, and increased significantly to 19.7 +/- 1.8% (P < 0.05) after
      perfusion over damaged arteries. In mixed neutrophil/platelet suspensions, the
      percentage of neutrophils that bind platelets increased significantly also, from
      10.8 +/- 1.6% at baseline to 39.7 +/- 2.9% (P < 0.05) after perfusion over
      damaged arteries compared with 69.7 +/- 2.5% with thrombin. This binding was
      completely inhibited by a recombinant soluble PSGL-1 (rPSGL-Ig) and anti-P
      selectin and PSGL-1-blocking monoclonal antibodies. The inhibitory effect of
      rPSGL-Ig correlated well with its binding to platelets (r = 0.98, P < 0.001).
      Circulating platelets are activated upon contact with damaged arteries, thereby
      enhancing their adhesive interactions with neutrophils via P-selectin and PSGL-1.
      Inhibition of this binding with rPSGL-Ig may constitute a target in the treatment
      of inflammatory and thrombotic reactions.

PMID- 11454929
TI  - Identification of angiotensin II type 2 (AT2) receptor domains mediating high
      affinity CGP 42112A binding and receptor activation.
AB  - Chimeric angiotensin II (AngII) receptors constructed of portions of the AT2
      receptor substituted into the AT1 receptor revealed the AT2 third extracellular
      loop and seventh transmembrane-spanning domain as major determinants for the
      ability to bind and activate in response to the AT2 receptor-selective agonist
      CGP 42112A. Radioligand binding experiments showed that chimeric AngII receptors
      possessing the AT2 third extracellular loop and seventh transmembrane-spanning
      domain bound CGP 42112A with high affinity approaching that of the wild-type AT2
      receptor. The presence of the AT2 third extracellular loop appeared sufficient
      for high-affinity CGP 42112A binding, which was further enhanced by the
      additional presence of the AT2 seventh transmembrane-spanning domain. Experiments
      with PD 123319, losartan, and [Sar1,Ile8]-AngII showed that increases in binding
      affinity associated with these domains were specific for CGP 42112A. Use of
      phosphoinositide hydrolysis as a functional index to measure activation of these
      chimeric AngII receptors further demonstrated that the AT2 seventh transmembrane
      spanning domain was especially critical for CGP 42112A to act as an agonist. The
      absence of the AT2 seventh transmembrane-spanning domain prohibited CGP 42112A
      induced activation of these receptors, even in the presence of high
      concentrations of CGP 42112A sufficient to saturate the binding sites. This study
      is the first to identify binding determinants of the AT2 receptor that are
      selective for CGP 42112A, and indicates that these determinants are at least
      partially distinct from those for the AT2-selective antagonist PD 123319. These
      differences may be a factor in the pharmacodynamic difference between these two
      ligands.

PMID- 11454930
TI  - 5-hydroxytryptamine3 (5-HT3) receptors mediate spinal 5-HT antinociception: an
      antisense approach.
AB  - To examine the role of the 5-hydroxytryptamine(1B) (5-HT1B) and 5-HT3 receptor
      subtypes in the analgesia produced by 5-HT (serotonin) agonists, we assessed the
      effect of antisense oligodeoxynucleotides (AODNs) designed to "knock down" the
      number of these receptor subtypes on analgesia produced by intrathecal (i.t.) 5
      HT, the 5-HT1B receptor agonist, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)
      pyrrolo[1,2-a]quinoxaline maleate (CGS-12066A), and the 5-HT3 receptor agonist, 2
      methyl-5-HT. Groups of mice (n = 17-20) were injected i.t. on days 1, 3, and 5
      with one of the AODNs, a mismatch oligo, or saline. On day 6, all mice were
      injected i.t. with 70.5 nmol of 5-HT, 44.4 nmol of CGS-12066A, or 49 nmol of 2
      methyl-5-HT by lumbar puncture. Following testing, spinal cords were rapidly
      removed and prepared for receptor binding assays. Treatment with AODN for 5-HT1B
      receptors produced a 70% reduction in ligand binding to this receptor subtype.
      After treatment with AODN for 5-HT3 receptors, ligand binding to this receptor
      subtype was undetectable. In mice tested with i.t. 5-HT, tail-flick analgesia was
      attenuated only in mice treated with the 5-HT3 receptor AODN. Mice treated with
      the AODN designed to knock down 5-HT(1B) receptors or with its mismatch oligo
      were not significantly different from controls. In mice tested with i.t.
      administration of CGS-12066A, none of the oligo treatments produced a significant
      attenuation of analgesia. In mice tested with i.t. administration of 2-methyl-5
      HT, only 5-HT3 receptor AODN attenuated analgesia. Thus, 5-HT and 2-methyl-5-HT
      analgesia are mediated by the 5-HT3 receptor subtype. However, spinal CGS-12066A
      analgesia appears not to be mediated by either the 5-HT1B or the 5-HT3 receptor
      subtypes.

PMID- 11454931
TI  - Compensatory up-regulation of nitric-oxide synthase isoforms in lead-induced
      hypertension; reversal by a superoxide dismutase-mimetic drug.
AB  - Chronic exposure to low levels of lead causes hypertension (HTN) that is, in
      part, due to increased inactivation of nitric oxide (NO) by reactive oxygen
      species (ROS). The latter results in functional NO deficiency and compensatory up
      regulation of NO synthase (NOS). We have previously shown evidence for increased
      hydroxyl radical (*OH) activity in rats with lead-induced HTN. Since in the
      biological systems *OH is primarily derived from superoxide (O2*) we hypothesize
      that lead-induced oxidative stress and HTN must be due to increased O2*
      production and as such could be ameliorated by administration of a cell-permeable
      O2* scavenger. We, therefore, studied the effects of the superoxide dismutase
      (SOD)-mimetic drug tempol (15 mmol/kg/day i.p. x 2 weeks) and placebo in lead
      exposed (given lead acetate, 100 ppm in the drinking water for 12 weeks) and
      normal control rats. Lead exposure resulted in a marked elevation of blood
      pressure, a significant reduction in urinary NO metabolites (NO(chi)) excretion,
      and up-regulations of endothelial and inducible NOS abundance in the kidney,
      aorta, and heart and of neuronal NOS in the cerebral cortex and brain stem.
      Administration of tempol ameliorated HTN, increased urinary NO(chi) excretion,
      and reversed the compensatory up-regulation of NOS isoforms in rats with lead
      induced HTN. These abnormalities recurred within 2 wk after discontinuation of
      tempol. In contrast to the lead-exposed rats, the normal control rats showed no
      change in either blood pressure, urinary NO(chi) excretion, or tissue NOS
      expression in response to either administration or discontinuation of tempol.
      Thus, the study supports the presence of increased O2* activity and its role in
      the pathogenesis of HTN and altered NO metabolism in lead-exposed animals.

PMID- 11454932
TI  - The relaxation induced by S-nitroso-glutathione and S-nitroso-N-acetylcysteine in
      rat aorta is not related to nitric oxide production.
AB  - S-nitroso-glutathione (GSNO) and S-nitroso-N-acetylcysteine (NACysNO) are
      nitrosothiols that release nitric oxide (NO) and mimic the effects of endogenous
      NO. This study investigated the relaxation induced by GSNO and NACysNO in rat
      aorta and the relation between relaxation and NO formation. Both compounds at
      concentrations from 10(-9) M to 10(-4) M relaxed the rat aorta in a concentration
      dependent manner. However, NO production depended on the concentration of
      nitrosothiols present and was detected only above 100 microM GSNO or NACysNO. To
      determine whether K+ channels are involved in the relaxation induced by
      nitrosothiols, the contractions were induced with KCl at concentrations of 30,
      60, or 90 mM. The concentration-effect curves for the relaxation induced by
      nitrosothiols were shifted to the right for all the K+ concentrations compared
      with aortas precontracted with phenylephrine. These results indicate the
      participation of K+ channels in the relaxation induced by GSNO and NACysNO. A
      selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one, significantly inhibited the relaxation induced by the
      nitrosothiols. The relaxation induced by GSNO and NACysNO was inhibited by the K+
      channel blockers glibenclamide, selective K(ATP) channels, and apamin, selective
      for low-conductance Ca2+-activated K+ channels in rat aorta, but was not
      inhibited by charybdotoxin, a potent and selective Ca2+-activated K+ channel
      blocker, or by 4-aminopyridine, a voltage-gated K+ channel blocker. These results
      indicate that relaxation induced by GSNO and NACysNO is partially due to
      activation of K(ATP) channels and partially due to activation of low-conductance
      Ca2+-activated K+ channels. However, the ability of the nitrosothiol compounds to
      overcome the inhibitory effect of high extracellular K+ concentrations suggests
      another mechanism of relaxation contributing to the nitrosothiol response. The
      most intriguing finding is that relaxation is not related to the NO produced in
      rat aorta.

PMID- 11454933
TI  - Ethanolamine transport in human placental brush-border membrane vesicles.
AB  - Pathways for transport of ethanolamine by human placental epithelia were
      investigated by measurement of [3H]ethanolamine uptake in brush-border membrane
      vesicles isolated by divalent cation precipitation. The presence of a conductive
      uptake pathway for ethanolamine was suggested by the marked stimulation of
      ethanolamine uptake to levels exceeding equilibrium induced by an inside-negative
      potassium diffusion potential. Evidence to suggest conductive ethanolamine uptake
      resulted from a mediated transport process included 1) the concentration
      dependent inhibition by choline; 2) trans-stimulation of choline and ethanolamine
      uptake by ethanolamine; and 3) substrate-specific inhibition by chemically
      related analogs. Transport of both choline and ethanolamine by a common
      facilitated diffusion mechanism is suggested by 1) trans-stimulation of choline
      uptake by ethanolamine; 2) mutual inhibition of conductive choline and
      ethanolamine uptake by ethanolamine and choline; 3) the effect of ethanolamine on
      the kinetics of conductive choline uptake; and 4) the rank order inhibition of
      choline and ethanolamine uptake by the same panel of chemical analogs. The
      present study identifies the presence of a facilitated diffusion mechanism as a
      brush-border membrane transport pathway for choline and ethanolamine accumulation
      by human placenta.

PMID- 11454934
TI  - Metabotropic neurosteroid/sigma-receptor involved in stimulation of nociceptor
      endings of mice.
AB  - In peripheral nociceptive flexor test, SA4503, (+)-pentazocine, and (+)-3
      (hydroxyphenyl)-N-(1-propyl)piperidine, representative sigma-receptor agonists,
      elicited dose-dependent flexor responses. These responses were blocked by sigma
      receptor antagonists NE-100 or BD1063, but not by pretreatments with antisense
      oligodeoxynucleotide for sigma1 binding protein. The sigma-agonists' nociception
      is attributed to the substance P (SP) release from nociceptor endings through
      activations of Galpha(i1) and phospholipase C (PLC). On the other hand, attomolar
      doses of neurosteroids such as dehydroepiandrosterone sulfate (DHEAS) and
      pregnenolone sulfate caused similar nociception, and they were blocked by
      progesterone (PROG). However, DHEAS nociception was not affected by pertussis
      toxin, but was completely inhibited by a PLC inhibitor or thapsigargin. Although
      the nociception by lower doses of DHEAS was abolished by diphenhydramine (DPH),
      H1 antagonist, there were dose-dependent responses by high doses of DHEAS in the
      presence of DPH. The responses by DHEAS in the presence of DPH were blocked by NE
      100, and those by (+)-pentazocine were blocked by PROG. All these findings
      suggest that two novel types of neurosteroid receptors exist, neuronal NS1/sigma
      type, which mediates activation of Galpha(i1) by neurosteroids and sigma
      agonists, followed by SP release from nociceptor endings; and NS2 type, which
      mediates histamine release from mast cells by very low doses of neurosteroids.

PMID- 11454935
TI  - Recognition and transport characteristics of nonpeptidic compounds by basolateral
      peptide transporter in Caco-2 cells.
AB  - Recent studies have revealed that diverse compounds lacking peptide bonds, such
      as valacyclovir and delta-aminolevulinic acid (delta-ALA), can be recognized by
      H+-coupled peptide transporters (PEPT1 and PEPT2). In the present study,
      recognition and transport characteristics of nonpeptidic compounds by the
      basolateral peptide transporter, which is distinct from PEPTs, were compared with
      those by PEPT1 using the human intestinal Caco-2 cells. [14C]Glycylsarcosine
      uptake via PEPT1 was inhibited by all nonpeptidic compounds tested. Similarly,
      most nonpeptidic compounds showed an inhibitory effect on [14C]glycylsarcosine
      uptake by the basolateral peptide transporter, although some kinds of nonpeptidic
      compounds, such as valine methyl ester, did not. Direct measurements of
      valacyclovir and delta-ALA transport revealed that both compounds were able to be
      transported by the basolateral peptide transporter. Because delta-ALA has been
      used recently in vitro and in clinical studies as an endogenous photosensitizer
      for photodynamic therapy, the intestinal transport characteristics of delta-ALA
      were further examined. Inhibition studies and Eadie-Hofstee plot analysis
      suggested that delta-ALA transport across the brush-border and basolateral
      membranes of the intestine was mainly mediated by peptide transporters. In
      addition, the apical-to-basolateral transport of delta-ALA was greater than that
      of the opposite direction. These findings provide the first evidence that the
      intestinal basolateral peptide transporter can recognize and transport
      nonpeptidic compounds, and play a definitive role in the absorption of delta-ALA.

PMID- 11454936
TI  - State-dependent block of rabbit vascular smooth muscle delayed rectifier and
      Kv1.5 channels by inhibitors of cytochrome P450-dependent enzymes.
AB  - The effects of the cytochrome P450 inhibitors clotrimazole, ketoconazole, and 1
      aminobenzotriazole (1-ABT) on native delayed rectifier (K(DR)) and cloned Kv1.5
      (RPV Kv1.5) K+ channels of rabbit portal vein (RPV) myocytes were determined
      using whole-cell and single channel patch-clamp analysis. Clotrimazole reduced
      K(DR) and RPV Kv1.5 whole-cell current with respective Kd values of 1.15 +/- 0.39
      and 1.99 +/- 0.6 microM. Clotrimazole acted via an open state blocking mechanism
      based on the following: 1) the early time course of K(DR) current activation was
      not affected, but inhibition developed with time during depolarizing steps and
      increased the rate of decay in current amplitude; 2) the inhibition was voltage
      dependent, increasing steeply over the voltage range of K(DR) activation; and 3)
      mean open time of RPV Kv1.5 channels in inside-out patches was decreased
      significantly. Ketoconazole reduced K(DR) current amplitude with a Kd value of 38
      +/- 3.2 microM. However, ketoconazole acted via a closed (resting) state blocking
      mechanism: 1) K(DR) amplitude was reduced throughout the duration of depolarizing
      steps and the rate of decay of current was unaffected, 2) there was no voltage
      dependence to the block by ketoconazole over the K(DR) activation range, and 3)
      ketoconazole did not affect mean open time of RPV Kv1.5 channels in inside-out
      membrane patches. 1-ABT between 0.5 and 3 mM did not affect native K(DR) or RPV
      Kv1.5 current of rabbit portal vein myocytes. Clotrimazole and ketoconazole, but
      not 1-ABT, suppress vascular K(DR) channels by direct, state-dependent block
      mechanisms not involving the modulation of cytochrome P450 enzyme activity.

PMID- 11454937
TI  - Pathophysiological roles of endogenous endothelin-1 in dogs with chronic heart
      failure produced by rapid right ventricular pacing.
AB  - This study was designed to analyze the pathophysiological role of the endogenous
      endothelin (ET) system and the therapeutic approach to congestive heart failure
      (CHF) with ET(A)/ET(B) receptor antagonists in a canine CHF model. After 3 weeks
      of rapid right ventricular pacing (240 beats/min), concentrations of
      immunoreactive ET-1 in dogs increased approximately 2-fold in plasma and in the
      left and right ventricles but not in the lung. There were no meaningful changes
      in the density and affinity of total ET receptors, or in the ratio of ET(A) to
      ET(B) receptors. To clarify the functional role of endogenous ET, we examined the
      effects of acute injection of J-104132 (1 and 3 mg/kg i.v.), an ET(A)/ET(B)
      receptor antagonist, on cardiovascular and renal function in dogs with CHF.
      Compared with vehicle, J-104132 at both doses significantly decreased pulmonary
      artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and mean
      arterial pressure (MAP), and increased cardiac output (CO) and renal blood flow.
      J-104132 had no effects on heart rate and cardiac contractility. In addition, we
      examined whether J-104132 has an additive effect in the presence of enalaprilat.
      J-104132 (1 mg/kg i.v.) administered after enalaprilat (0.05 mg/kg i.v.) induced
      further decreases in MAP, PCWP and PAP, and further increases in CO, resulting in
      further decreases in total peripheral resistance. These results indicate that the
      endogenous ET system is exaggerated in CHF and has a detrimental effect on
      cardiac function. Therefore, J-104132 given alone or as combination therapy may
      play a beneficial role in the treatment of CHF in humans.

PMID- 11454938
TI  - Acute ethanol administration oxidatively damages and depletes mitochondrial dna
      in mouse liver, brain, heart, and skeletal muscles: protective effects of
      antioxidants.
AB  - Ethanol metabolism causes oxidative stress and lipid peroxidation not only in
      liver but also in extra-hepatic tissues. Ethanol administration has been shown to
      cause oxidative degradation and depletion of hepatic mitochondrial DNA (mtDNA) in
      rodents, but its in vivo effects on the mtDNA of extra-hepatic tissues have not
      been assessed. We studied the effects of an acute intragastric ethanol
      administration (5 g/kg) on brain, heart, skeletal muscle, and liver mtDNA in
      mice. Ethanol administration caused mtDNA depletion and replacement of its
      supercoiled form by linearized forms in all tissues examined. Maximal mtDNA
      depletion was about similar (ca. 50%) in all organs studied. It occurred 2 h
      after ethanol administration in heart, skeletal muscle, and liver but after 10 h
      in brain. This mtDNA depletion was followed by increased mtDNA synthesis. A
      secondary, transient increase in mtDNA levels occurred 24 h after ethanol
      administration in all organs. In hepatic or extra-hepatic tissues, mtDNA
      degradation and depletion were prevented by 4-methylpyrazole, an inhibitor of
      ethanol metabolism, and attenuated by vitamin E, melatonin, or coenzyme Q, three
      antioxidants. In conclusion, our study shows for the first time that ethanol
      metabolism also causes oxidative degradation of the mitochondrial genome in
      brain, heart, and skeletal muscles. These effects could contribute to the
      development of (cardio)myopathy and brain injury in some alcoholic patients.
      Antioxidants prevent these effects in mice and could be useful in persevering
      drinkers.

PMID- 11454939
TI  - Cytokine-induced iNOS expression in C6 glial cells: transcriptional inhibition by
      ethanol.
AB  - The effect of cytokines, lipopolysaccharide, and ethanol on inducible nitric
      oxide synthase (iNOS) expression was studied in C6 glial cells. Maximal induced
      activity, measured by the accumulation of nitrite in culture medium, occurred
      following treatment with lipopolysaccharide and interferon-gamma. Each cytokine
      alone was ineffective, whereas an optimal combination of interleukin-1beta, tumor
      necrosis factor-alpha, and interferon-gamma was near maximal, indicating
      synergistic interactions. Other combinations caused submaximal activity. Ethanol
      is known to suppress iNOS expression in C6 cells induced by a phorbol ester plus
      lipopolysaccharide. The current work shows ethanol also suppresses cytokine
      induced iNOS expression and reduces interleukin-1beta and tumor necrosis factor
      alpha potency without affecting interferon-gamma potency. Ethanol-mediated
      reductions in cytokine-induced iNOS mRNA and immunoreactive protein levels
      suggested an effect on gene transcription. Therefore, C6 cells stably expressing
      1846 and 526 base fragments of the rat iNOS gene promoter fused to a luciferase
      reporter gene were prepared and characterized and used to study the effect of
      ethanol on iNOS promoter activity. Promoter activity in stable transfected C6
      cells was inhibited by ethanol exposure with a similar concentration dependence
      as observed for inhibition of nitrite production, indicating that iNOS inhibition
      by ethanol is transcriptional. Furthermore, ethanol inhibition of the 526 base
      fragment activity, which lacks interferon-gamma enhancement of lipopolysaccharide
      induced luciferase activity, confirmed that interferon-gamma-responsive elements
      do not participate in acute ethanol-induced inhibition of rat iNOS gene
      transcription.

PMID- 11454940
TI  - SL651498: an anxioselective compound with functional selectivity for alpha2- and
      alpha3-containing gamma-aminobutyric acid(A) (GABA(A)) receptors.
AB  - SL651498 [6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H
      pyrido[3,4-b]indol-1-one] is a novel pyridoindole derivative that displays high
      affinity for rat native GABA(A) receptors containing alpha(1) (K(i) = 6.8 nM) and
      alpha2 (K(i) = 12.3 nM) subunits, and weaker affinity for alpha5-containing
      GABA(A) receptors (K(i) = 117 nM). Studies on recombinant rat GABA(A) receptors
      confirm these data (K(i), alpha1beta2gamma2 = 17, alpha2beta2gamma2 = 73,
      alpha5beta3gamma2 = 215 nM) and indicate intermediate affinity for the
      alpha3beta2gamma2 subtype (K(i) = 80 nM). SL651498 behaves as a full agonist at
      recombinant rat GABA(A) receptors containing alpha2 and alpha3 subunits and as a
      partial agonist at recombinant GABA(A) receptors expressing alpha1 and alpha5
      subunits. SL651498 elicited anxiolytic-like activity similar to that of diazepam
      [minimal effective dose (MED): 1-10 mg/kg, i.p.] in three conflict models, in the
      elevated plus-maze, the light/dark test, and the defense test battery in rats and
      mice. Results from activity tests and electroencephalogram analysis indicated
      that SL651498 induced muscle weakness, ataxia, or sedation at doses much higher
      than those producing anxiolytic-like activity (MED > or = 30 mg/kg, i.p.).
      Repeated treatment for 10 days with SL651498 (30 mg/kg, i.p., b.i.d.) in mice was
      not associated with the development of tolerance to its anticonvulsant effects or
      physical dependence. Furthermore, SL651498 was much less active than diazepam in
      potentiating the depressant effects of ethanol in mice. The "anxioselective"
      profile of SL651498 points to a major role for GABA(A) alpha2 subtype in
      regulating anxiety and suggests that selectively targeting GABA(A) receptor
      subtypes can lead to drugs with increased clinical specificity.

PMID- 11454941
TI  - Gender-dependent enhanced adult neurotoxic response to methamphetamine following
      fetal exposure to the drug.
AB  - Methamphetamine use by females of child-bearing age has become a major public
      health concern in terms of the long-term risk to the exposed fetus. We examined
      the possibility of enhanced adult neurotoxic potential of the drug in offspring
      that had been exposed to methamphetamine in utero during gestational days 7 to
      18. While basal levels of monoamines were not affected by prenatal exposure to
      methamphetamine, we observed an enhanced neurotoxicity in adult male offspring
      following drug challenge with effects localized primarily to the dopaminergic
      nigrostriatal projection. This was evidenced by greater methamphetamine-induced
      reductions of dopaminergic markers in the striatum [dopamine (DA),
      dihydroxyphenylacetic acid, homovanillic acid (HVA), and 3-methoxytyramine (3
      MT)] and ventral brainstem (DA) of prenatal methamphetamine-treated males
      compared with saline-treated animals. Some effects of prenatal methamphetamine
      exposure were observed in female offspring, but these were limited to striatal
      levels of 3-MT and HVA. Differential gender sensitivity to the neurotoxic effect
      of methamphetamine was shown to be correlated with hyperthermic response.
      Hyperthermic effects, however, do not account for the increased susceptibility of
      prenatal methamphetamine-treated males to drug-induced striatal DA neurotoxicity
      since methamphetamine challenge did not evoke a significantly greater
      hyperthermic response in these animals compared with prenatal saline-treated
      males. The findings raise the concern that male methamphetamine abusers may be at
      risk for an enhanced neurotoxic risk if they were exposed to the drug in utero.

PMID- 11454942
TI  - Amino acid transporters involved in luminal transport of mercuric conjugates of
      cysteine in rabbit proximal tubule.
AB  - The primary aim of the present study was to test the hypothesis that amino acid
      transport systems are involved in absorptive transport of dicysteinylmercury
      (cysteine-Hg-cysteine). Luminal disappearance flux [JD, fmol x min(-1) (mm
      tubular length)(-1)] of inorganic mercury (Hg2+), in the form of
      dicysteinylmercury, was measured in isolated perfused S2 segments with various
      amino acids or amino acid analogs in the luminal compartment under one of two
      conditions, in the presence or absence of Na+. The control perfusion fluid
      contained 20 microM dicysteinylmercury. Replacing Na+ in both the bathing and
      perfusing solutions with N-methyl-D-glucamine reduced the JD of Hg2+ by about
      40%. Nine amino acids and two amino acid analogs were coperfused individually (at
      millimolar concentrations) with dicysteinylmercury. The amino acids and amino
      acid analogs that had the greatest effect on the JD of Hg2+ were L-cystine, L
      serine, L-histidine, L-tryptophan, and 2-(-)-endoamino-bicycloheptane-2
      carboxylic acid. The greatest reduction (76%) in the total JD of Hg2+ occurred
      when L-cystine was coperfused with dicysteinylmercury in the presence of Na+.
      Overall, the current findings indicate that Hg2+ is transported from the lumen
      into proximal tubular epithelial cells via amino acid transporters that recognize
      dicysteinylmercury. In addition, the data indicate that multiple amino acid
      transporters are involved in the luminal uptake of dicysteinylmercury, including
      the Na+-dependent low-affinity L-cystine, B(0), and ASC systems and the Na+
      independent L-system. Furthermore, the transport data obtained when L-cystine was
      added to the luminal fluid indicate strongly that dicysteinylmercury is likely
      transported as a molecular homolog of L-cystine.

PMID- 11454943
TI  - Induction of Tmolt4 leukemia cell death by 3,3-disubstituted-6,6-pentamethylene
      1,5-diazabicyclo[3.1.0]hexane-2-4-diones: specificity for type II inosine 5'
      monophasphate dehydrogenase.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the
      de novo pathway for synthesis of guanine nucleotides, is essential for normal
      cell proliferation and function. New derivatives of the 1,5
      diazabicyclo[3.1.0]hexane-2,4-diones were synthesized and examined for
      antiproliferative effects and selective inhibition of human IMPDH type II
      activity. The 3,3-disubstituted-6,6-pentamethylene-1,5-diazabicyclo[3.1.0]hexane
      2,4-diones proved to be effective antiproliferative agents in tumor cell lines
      derived from murine and human leukemias, lymphomas, uterine carcinoma, glioma,
      and breast effusion with ED50 values (concentration of compound that inhibits 50%
      of cell growth) ranging from 3.3 to 16 microM. The agents acted as
      antimetabolites suppressing de novo purine biosynthesis at the key regulatory
      enzyme IMPDH, resulting in the specific suppression of dGTP pool levels by 19 to
      64% and DNA synthesis by 39 to 68%. The derivatives were specific inhibitors of
      IMPDH type II activity as opposed to type I, acting in a competitive manner with
      respect to inosine 5'-monophosphate, K(i) values of 44.2 to 62 microM. In
      addition, effects of agents on Tmolt4 cell growth and DNA synthesis could be
      reversed by coincubation with guanosine. Unlike mycophenolic acid and tiazofurin,
      the 6,6-pentamethylene-1,5-diazabicyclo[3.1.0]hexane-2,4-diones specifically
      targeted type II IMPDH, where activity is increased in replicating or neoplastic
      cells, and did not suppress type I activity, where expression is relatively
      unaffected by cell proliferation or transformation. Agents were not inhibitors of
      normal human lung fibroblast cell growth, WI-38, most likely due to the observed
      isoform selectivity.

PMID- 11454944
TI  - Effect of perinatal buprenorphine exposure on development in the rat.
AB  - The developmental effects of exposure to various doses of buprenorphine,
      methadone, or water during the perinatal period were studied in the rat. Rats
      were exposed to buprenorphine (0.3, 1.0, or 3.0 mg/kg/day), methadone (9
      mg/kg/day), and/or water prenatally, postnatally, or both pre- and postnatally,
      via maternally implanted osmotic minipumps. Fetal and maternal mortality and
      morbidity were assessed, as well as the acquisition of several developmental
      milestones, pup weight gain, precipitated withdrawal, and the antinociceptive
      effect of morphine. Although perinatal exposure to buprenorphine failed to
      produce severe maternal and fetal or neonatal mortality, it was associated with a
      significant amount of perinatal mortality and perturbations of pup development.
      Pups developed physical dependence to both drugs, as evidenced by the ability of
      naloxone challenge to precipitate withdrawal. Both drugs induced tolerance to the
      antinociceptive effects of morphine in the tail-flick test. The effects of
      buprenorphine varied with the dose used, and the highest dose did not always
      produce the greatest effect. There were some similarities between the effects of
      perinatal buprenorphine and perinatal methadone; however, differences were also
      observed between the effects of the two drugs, which may be related to the
      different affinities and efficacies of the drugs at different opioid receptor
      subtypes.

PMID- 11454945
TI  - Liver targeting of interferon-beta with a liver-affinity polysaccharide based on
      metal coordination in mice.
AB  - Frequent and high-dose i.v. injections of interferon-beta (IFN-beta) have been
      used clinically to treat patients with viral hepatitis despite various side
      effects. Because side effects are caused by the systemic effects of IFN-beta, the
      purpose of this study was to target the drug specifically to the liver, thus
      reducing the adverse events. A chelating residue, diethylenetriaminepentaacetic
      acid (DTPA), was introduced to pullulan, a water-soluble polysaccharide with a
      high affinity for the liver. Murine IFN-beta could be coordinately conjugated
      with the DTPA-pullulan by simple mixing in an aqueous solution containing zinc
      ion (Zn2+). Intravenous injection of the IFN-beta-DTPA-pullulan conjugate with
      Zn2+ coordination enhanced liver induction of an antiviral enzyme, 2',5'
      oligoadenylate synthetase (2-5AS), to a greater extent than that by free IFN
      beta, although the 2-5AS levels in the liver depended on the mixing ratio of the
      IFN-beta/DTPA residue of DTPA-pullulan/Zn2+. In addition, the duration of the
      liver 2-5AS induction by the IFN-beta-DTPA-pullulan conjugate with Zn2+
      coordination was longer than that by free IFN-beta. The liver targeting of IFN
      beta by DTPA-pullulan with Zn2+ coordination may be a promising IFN therapy.

PMID- 11454946
TI  - Pharmacological characterization of the novel nonpeptide orphanin FQ/nociceptin
      receptor agonist Ro 64-6198: rapid and reversible desensitization of the ORL1
      receptor in vitro and lack of tolerance in vivo.
AB  - The novel nonpeptide orphanin FQ/nociceptin (OFQ/N) ligand [(1S,3aS)-8
      (2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4
      one] (Ro 64-6198) was characterized in vitro and in vivo for its agonistic
      potential. Ro 64-6198 was 130- to 3500-fold selective for the OFQ/N receptor
      (ORL1) compared with opiate receptors. In the cAMP inhibition assay, Ro 64-6198
      was a full agonist at the ORL1 and a partial agonist at the mu opiate receptor.
      When human embryonic kidney 293 cells stably expressing the human ORL1 receptor
      were pre-exposed (30 min) to either OFQ/N or Ro 64-6198, the ability of both
      agonists to inhibit forskolin-mediated cAMP accumulation was strongly reduced,
      indicating a functional desensitization of the second messenger cascade. However,
      acidic washes of OFQ/N-exposed cells fully restored the sensitivity of the ORL1
      receptor for agonists. In contrast, the cAMP response in Ro 64-6198-exposed cells
      remained impaired after acidic washes, suggesting sustained receptor
      internalization at 30 min. In agreement with this finding, the number of cell
      surface ORL1 receptors was significantly reduced after Ro 64-6198 pre-exposure,
      and this effect could be blocked with high sucrose concentrations. When Ro 64
      6198 was chronically administered to rats, no signs of tolerance to its
      anxiolytic-like effects were detected following 15 days of daily drug exposure.
      In agreement with the behavioral results, Ro 64-6198 was able to reduce brain
      ORL1 binding sites in both acutely and chronically treated rats. Full recovery of
      ORL1 binding sites was observed 24 h after Ro 64-6198 administration with a t1/2
      of approximately 5.5 h. These data show that nonpeptide agonists at the ORL1
      receptor have a good clinical potential as anxiolytics without causing tolerance.

PMID- 11454947
TI  - Changes in erythropoietin pharmacokinetics following busulfan-induced bone marrow
      ablation in sheep: evidence for bone marrow as a major erythropoietin elimination
      pathway.
AB  - The contribution of the bone marrow to in vivo erythropoietin (EPO) elimination
      was evaluated by determining EPO pharmacokinetic (PK) parameters in five adult
      sheep in a paired manner before and after chemotherapy-induced marrow ablation.
      After busulfan-induced bone marrow ablation, EPO PK demonstrated progressive
      decreases in plasma clearance (CL), elimination half-life [t1/2(beta)], and
      volume of distribution at steady state (Vss) with concomitant increases in mean
      residence time (MRT). Eight days after beginning busulfan treatment, there were
      no further changes in CL, t1/2(beta), MRT, and Vss. Only 20% of baseline CL
      remained by day 8. The volume of distribution (Vc) and distribution half-life
      [t1/2(alpha)], in contrast, remained unchanged from baseline. White blood cell
      counts and reticulocytes gradually declined after the start of marrow ablation.
      Examination of bone marrow core biopsy samples obtained on day 10 revealed less
      than 10% of baseline marrow cellularity. No colony-forming unit erythroid (CFU-E)
      colonies were found after 6 days of incubation for bone marrow aspirates drawn at
      days 8 and 13 following busulfan treatment, whereas pre-busulfan aspirates
      yielded 29 CFU-E colonies per 10(5) cells in CFU-E cultures. Treatment of a sheep
      with 5-fluorouracil showed changes in PK parameters that were similar to the
      results from treatment with busulfan. The present study indicates that the bone
      marrow significantly contributes to the elimination of EPO in vivo.

PMID- 11454948
TI  - Activation of Akt1 by human 5-hydroxytryptamine (serotonin)1B receptors is
      sensitive to inhibitors of MEK.
AB  - Akt1/protein kinase B and the mitogen-activated protein (MAP) kinases
      extracellular signal-regulated kinase 1 (ERK1) and ERK2 have been shown to
      promote cell survival in a cell-specific manner. Since many receptors activate
      both pathways, inhibitors are commonly used to study the relative role of each
      pathway. In the present study, we examined the effects of PD098059 and U0126, two
      structurally dissimilar inhibitors of MAP kinase kinase (MEK1/2), on the
      activation of ERK and Akt stimulated by human 5-hydroxytryptamine(1B) (serotonin)
      (5-HT1B) receptors. Surprisingly, pathways for activation of both ERK and Akt
      were found to be sensitive to the two MEK inhibitors at concentrations commonly
      used to selectively inhibit the activation of ERK. Both compounds caused complete
      inhibition of phosphorylation of ERK and a maximal 60% inhibition of 5-HT1B
      receptor-mediated phosphorylation of Akt. Inhibition of Akt activation required
      almost complete inhibition of ERK. Transfection with cDNA for activated forms of
      MEK1/2 caused increased phosphorylation of ERK but not of Akt, demonstrating that
      independent activation of MEK/ERK was insufficient for activation of Akt.
      Therefore, it is not clear whether inhibition of activation of Akt resulted from
      selective inhibition of MEK or from additional actions on other unidentified
      common pathways. Nevertheless, our findings that PD098059 and U0126 inhibit
      activation of Akt at commonly used concentrations demonstrate that in at least
      some systems, these compounds inhibit activation of both ERK and Akt, and cannot
      be used to discern the relative roles of each pathway in mediating cellular
      responses.

PMID- 11454949
TI  - Dopamine D2 receptor inhibition of adenylyl cyclase is abolished by acute ethanol
      but restored after chronic ethanol exposure (tolerance).
AB  - Dopamine D2 (D2) receptors seem to mediate reinforcing responses to addicting
      drugs. A stably transfected NG108-15 cell line expressing the long form of the
      rat brain D2 receptor (D2L) was used to determine how ethanol modifies D2
      receptor coupling to adenylyl cyclase. Activation of D2L receptors by the D2
      receptor-specific agonist R-(-)-2,10,11-trihydroxy-N-propylnorapomorphine
      hydrobromide (NPA) inhibits both basal and receptor-stimulated cAMP production in
      these cells. Ethanol added acutely prevents D2L receptor inhibition of cAMP
      production. After chronic exposure to ethanol, however, D2L receptor coupling to
      adenylyl cyclase becomes tolerant to rechallenge with ethanol, i.e., ethanol no
      longer inhibits D2L receptor coupling and NPA inhibition of cAMP production is
      restored. Acute ethanol does not change NPA binding to D2 receptor in cell
      membranes but abolishes guanosine-5'-O-(3-thio)triphosphate induction of a lower
      affinity state; chronic ethanol is without effect. The protein kinase A (PKA)
      inhibitor adenosine 3',5' cyclic monophosphorothioate, Rp-isomer, prevents acute
      ethanol inhibition of D2L receptor coupling. In contrast, the PKA activator
      adenosine 3',5' cyclic monophosphorothioate, Sp-isomer, reverses chronic ethanol
      induced tolerance of D2L receptor coupling, restoring coupling to an ethanol
      sensitive state. These results suggest that D2L receptor coupling to adenylyl
      cyclase via G(i) develops tolerance to ethanol inhibition, which appears to be
      influenced by PKA activity.

PMID- 11454950
TI  - Monovalent anions differentially modulate coupling of the beta2-adrenoceptor to
      G(s)alpha splice variants.
AB  - The beta2-adrenoceptor (beta2AR) fused to the long splice variant of G(s)alpha
      (G(s)alphaL), but not the beta2AR fused to the short splice variant of G(s)alpha
      (G(s)alphaS) shows the hallmarks of high constitutive activity, i.e., strong
      activation of adenylyl cyclase (AC) by GTP and strong inhibition of AC by inverse
      agonist. These coupling differences are the result of differences in GDP affinity
      of G(s)alpha splice variants. The aim of this study was to identify experimental
      variables that differentially affect beta2AR coupling to G(s)alphaS and
      G(s)alphaL. NaCl substantially reduced agonist-independent AC activation by GTP
      and inverse agonist inhibition and enhanced agonist stimulation of AC in Sf9
      insect cell membranes expressing the beta2AR-G(s)alphaL fusion protein. Salts
      reduced inverse agonist inhibition and increased agonist stimulation of AC in the
      order of efficiency NaI approximately KI > NaBr approximately KBr > NaCl
      approximately LiCl approximately KCl approximately RbCl approximately CsCl
      approximately choline chloride, indicating that monovalent anions determine salt
      effects. Salts inhibited guanosine 5'-O-(3-thiotriphosphate)-mediated AC
      activation by G(salphaL) without beta2AR in the order of efficiency NaI > NaBr >
      NaCl. NaCl enhanced the affinity of G(s)alphaL for GDP. Salts had much smaller
      effects on beta2AR ligand regulation of AC in membranes expressing beta2AR
      G(s)alphaS than in membranes expressing beta2AR-G(s)alphaL. These data are
      explained by a model in which anions increase the GDP affinity of G(s)alphaL more
      efficiently than the GDP affinity of G(s)alphaS, and, thereby, decrease the
      efficiency of the agonist-free beta2AR and increase the efficiency of the agonist
      occupied beta2AR at promoting GDP dissociation from G(s)alphaL. Thus, monovalent
      anions differentially regulate beta2AR-coupling to G(s)alphaS and G(s)alphaL.

PMID- 11454951
TI  - Pharmacodynamic and pharmacokinetic characterization of poly(ethylene glycol)
      conjugation to met-enkephalin analog [D-Pen2, D-Pen5]-enkephalin (DPDPE).
AB  - Poly(ethylene glycol), or PEG, conjugation to proteins and peptides is a growing
      technology used to enhance efficacy of therapeutics. This investigation assesses
      pharmacodynamic and pharmacokinetic characteristics of PEG-conjugated [D-Pen2,D
      Pen5]-enkephalin (DPDPE), a met-enkephalin analog, in rodent (in vivo, in situ)
      and bovine (in vitro) systems. PEG-DPDPE showed increased analgesia (i.v.)
      compared with nonconjugated form (p < 0.01), despite a 172-fold lower binding
      affinity for the delta-opioid receptor. [125I]PEG-DPDPE had a 36-fold greater
      hydrophilicity (p < 0.01) and 12% increase in the unbound plasma protein fraction
      (p < 0.01), compared with [(125)I]DPDPE. [125I]PEG-DPDPE had a 2.5-fold increase
      in elimination half-life (p < 0.01), 2.7-fold decrease in volume of distribution
      (p < 0.01), and a 7-fold decrease in plasma clearance rate (p < 0.01) to
      [125I]DPDPE. Time course distribution showed significant concentration
      differences (p < 0.01) in plasma, whole blood, liver, gallbladder,
      gastrointestinal (GI) content, GI tract, kidneys, spleen, urine, and brain
      (brain, p < 0.05), between the conjugated and nonconjugated forms. Increased
      brain uptake of [(125)I]PEG-DPDPE corresponded to analgesia data. [125I]PEG-DPDPE
      in brain was shown to be 58.9% intact, with 41.1% existing as [125I]DPDPE
      (metabolite), whereas [125I]DPDPE was 25.7% intact in the brain (at 30 min). In
      vitro P-glycoprotein affinity was shown for [125I]DPDPE (p < 0.01) but not shown
      for [125I]PEG-DPDPE. In vitro saturable uptake, with 100 microM DPDPE, was shown
      for [125I]PEG-DPDPE (p < 0.05). In this study, PEG-conjugated DPDPE seems to act
      as a prodrug, enhancing peripheral pharmacokinetics, while undergoing hydrolysis
      in the brain and allowing nonconjugated DPDPE to act at the receptor.

PMID- 11454952
TI  - Carbachol inhibits the L-type Ca2+ current augmented by 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in guinea pig ventricular
      myocytes: calcium-sensitivity hypothesis for muscarinic inhibition.
AB  - The L-type Ca2+ current [I(Ca(L))] increases with time after patch rupture in
      guinea pig ventricular myocytes dialyzed with pipette solutions containing > or
      =20 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid ([BAPTA]pip).
      I(Ca(L)) progressively increases because BAPTA chelates subsarcolemmal Ca2+ to
      disinhibit cardiac adenylyl cyclase (AC) activity. We studied inhibition by
      carbachol (CCh) of I(Ca(L)) (22-24 degrees C). At 40 mM [BAPTA]pip, 100 microM
      CCh reversibly suppressed I(Ca(L)) maximally by 42%; half-maximal inhibition
      (20%) required 1 microM. Atropine antagonized the CCh effect on BAPTA-stimulated
      I(Ca(L),) as did dialysis with 50 microM guanosine-5'-O-(3-thio)triphosphate. At
      20, 30, and 40 mM [BAPTA]pip, I(Ca(L)) increased by 6.7 +/- 1.8, 10.1 +/- 1.4,
      and 11.3 +/- 1.2 pA/pF, respectively. Inhibition by 100 microM CCh averaged -1.8
      +/- 0.6, -2.3 +/- 0.4, and -4.1 +/- 0.4 pA/pF at 20, 30, and 40 mM [BAPTA](pip),
      respectively. Dialysis of the AC inhibitor 2'-dAMP (100 microM) suppressed
      I(Ca(L)) run up in 40 mM BAPTA and its inhibition by CCh. Replacing 1.8 mM
      external Ca2+ with Ba2+, which lacks high-affinity regulatory sites on AC,
      suppressed CCh-induced inhibition. Neither I(Ca(L)) run up nor its inhibition by
      CCh occurred when 40 mM EGTA, a slower chelator, replaced BAPTA. Our results
      support the AC disinhibition hypothesis for BAPTA. We propose that CCh inhibits
      I(Ca(L)) in BAPTA by increasing either AC sensitivity to inhibition by ambient
      Ca2+ or the activity of the inhibitory guanine nucleotide binding protein.

PMID- 11454953
TI  - Local Ca(2+) transients and distribution of BK channels and ryanodine receptors
      in smooth muscle cells of guinea-pig vas deferens and urinary bladder.
AB  - 1. The relationship between Ca(2+) sparks spontaneously occurring at rest and
      local Ca(2+) transients elicited by depolarization was analysed using two
      dimensional confocal Ca(2+) images of single smooth muscle cells isolated from
      guinea-pig vas deferens and urinary bladder. The current activation by these
      Ca(2+) events was also recorded simultaneously under whole-cell voltage clamp. 2.
      Spontaneous transient outward currents (STOCs) and Ca(2+) sparks were
      simultaneously detected at -40 mV in approximately 50 % of myocytes of either
      type. Ca(2+) sparks and corresponding STOCs occurred repetitively in several
      discrete sites in the subplasmalemmal area. Large conductance Ca(2+)-dependent
      K(+) (BK) channel density in the plasmalemma near the Ca(2+) spark sites
      generating STOCs was calculated to be 21 channels microm(-2). 3. When myocytes
      were depolarized from -60 to 0 mV, several local Ca(2+) transients were elicited
      within 20 ms in exactly the same peripheral sites where sparks occurred at rest.
      The local Ca(2+) transients often lasted over 300 ms and spread into other areas.
      The appearance of local Ca(2+) transients occurred synchronously with the
      activation of Ca(2+)-dependent K(+) current (I(K,Ca)). 4. Immunofluorescence
      staining of the BK channel alpha-subunit (BKalpha) revealed a spot-like pattern
      on the plasmalemma, in contrast to the uniform staining of voltage-dependent
      Ca(2+) channel alpha1C subunits along the plasmalemma. Ryanodine receptor (RyR)
      immunostaining also suggested punctate localization predominantly in the
      periphery. Double staining of BKalpha and RyRs revealed spot-like co-localization
      on/beneath the plasmalemma. 5. Using pipettes of relatively low resistance,
      inside-out patches that included both clustered BK channels at a density of over
      20 channels microm(-2) and functional Ca(2+) storage sites were obtained at a low
      probability of approximately 5%. The averaged BK channel density was 3-4 channels
      microm(-2) in both types of myocyte. 6. These results support the idea that a
      limited number of discrete sarcoplasmic reticulum (SR) fragments in the
      subplasmalemmal area play key roles in the control of BK channel activity in two
      ways: (i) by generating Ca(2+) sparks at rest to activate STOCs and (ii) by
      generating Ca(2+) transients presumably triggered by sparks during an action
      potential to activate a large I(K,Ca) and also induce a contraction. BK channels
      and RyRs may co-localize densely at the junctional areas of plasmalemma and SR
      fragments, where Ca(2+) sparks occur to elicit STOCs.

PMID- 11454954
TI  - Effects of ryanodine on calcium sparks in cut twitch fibres of Rana temporaria.
AB  - 1. Localized calcium release events (calcium sparks) were studied in voltage
      clamped cut twitch fibres of Rana temporaria. 2. A histogram of thousands of
      spontaneous sparks displayed a monotonically decreasing amplitude distribution
      from the low to the high limit of > 7 DeltaF/F(0) units. 3. Several effects of
      low micromolar concentrations of ryanodine (0.4-2 microM) on spontaneous sparks,
      reproducing the agent's effects on single ryanodine receptor channel current in
      bilayers, were observed collectively for the first time in live fibres, namely
      (a) increases in spark frequency followed by (b) conversions of sparks into
      steady glows lasting tens of seconds, (c) occasional interruptions of the glows
      by brief gaps of darkness, and (d) abolition of sparks at the locations of the
      glows. The glow could reflect the incessant Ca(2+) flux through a single (or a
      few) calcium release channel locked in the semi-open state, which was allowed to
      make occasional transitions to the closed state but not to the fully open state.
      4. Higher concentrations of ryanodine (> or = 20 microM) suppressed the
      spontaneous sparks effectively and permanently, presumably by deactivating the
      ryanodine receptors. 5. Depolarization-evoked sparks elicited with small pulses
      had higher frequencies and larger amplitudes than spontaneous sparks and were
      abolished by both concentrations of ryanodine. 6. With 1-2 microM ryanodine,
      however, a uniform non-sparking calcium release persisted during the pulse, with
      the globally averaged increase in fluorescence intensity being about half that of
      the control. A possible origin of this non-sparking release may be related to the
      structural coupling between the voltage sensors and the ryanodine receptors that
      can exist only in live fibres but not in the bilayer preparation.

PMID- 11454955
TI  - Calcium currents and transients in co-cultured contracting normal and Duchenne
      muscular dystrophy human myotubes.
AB  - 1. The goal of the present study was to investigate differences in calcium
      movements between normal and Duchenne muscular dystrophy (DMD) human contracting
      myotubes co-cultured with explants of rat spinal cord with attached dorsal root
      ganglia. Membrane potential, variations of intracellular calcium concentration
      and T- and L-type calcium currents were recorded. Further, a descriptive and
      quantitative study by electron microscopy of the ultrastructure of the co
      cultures was carried out. 2. The resting membrane potential was slightly less
      negative in DMD (-61.4 +/- 1.1 mV) than in normal myotubes (-65.5 +/- 0.9 mV).
      Both types of myotube displayed spontaneous action potentials (mean firing
      frequency, 0.42 and 0.16 Hz, respectively), which triggered spontaneous calcium
      transients measured with Indo-1. 3. The time integral under the spontaneous
      Ca(2+) transients was significantly greater in DMD myotubes (97 +/- 8 nM s) than
      in normal myotubes (67 +/- 13 nM s). 4. The L- and T-type current densities
      estimated from patch-clamp recordings were smaller in DMD cells (2.0 +/- 0.5 and
      0.90 +/- 0.19 pA pF(-1), respectively) than in normal cells (3.9 +/- 0.7 and 1.39
      +/- 0.30 pA pF(-1), respectively). 5. The voltage-dependent inactivation
      relationships revealed a shift in the conditioning potential at which
      inactivation is half-maximal (V(h,0.5)) of the T- and L-type currents towards
      less negative potentials, from -72.1 +/- 0.7 and -53.7 +/- 1.5 mV in normal cells
      to -61.9 +/- 1.4 and -29.2 +/- 1.4 mV in DMD cells, respectively. 6. Both
      descriptive and quantitative studies by electron microscopy suggested a more
      advanced development of DMD myotubes as compared to normal ones. This conclusion
      was supported by the significantly larger capacitance of the DMD myotubes (408 +/
      45 pF) than of the normal myotubes (299 +/- 34 pF) of the same apparent size. 7.
      Taken together, these results show that differences in T- and L-type calcium
      currents between normal and DMD myotubes cannot simply explain all observed
      alterations in calcium homeostasis in DMD myotubes, thus suggesting that other
      transmembrane calcium transport mechanisms must also be altered in DMD myotubes
      compared with normal myotubes.

PMID- 11454956
TI  - Is myosin phosphatase regulated in vivo by inhibitor-1? Evidence from inhibitor-1
      knockout mice.
AB  - 1. The Ca(2+) sensitivity of smooth muscle contractility is modulated via
      regulation of phosphatase activity. Protein phosphatase inhibitor-1 (I-1) is the
      classic type-1 phosphatase inhibitor, but its presence and role in cAMP-dependent
      protein kinase (PKA) modulation of smooth muscle is unclear. To address the
      relevance of I-1 in vivo, we investigated smooth muscle function in a mouse model
      lacking the I-1 protein (I-1((-/-)) mice). 2. Significant amounts of I-1 protein
      were detected in the wild-type (WT) mouse aorta and could be phosphorylated by
      PKA, as indicated by (32)P-labelled aortic extracts from WT mice. 3. Despite the
      significant presence of I-1 in WT aorta, phenylephrine and KCl concentration-
      isometric force relations in the presence or absence of the PKA pathway activator
      isoproterenol (isoprenaline) were unchanged compared to I-1((-/-)) aorta. cGMP
      dependent protein kinase (PKG) relaxation pathways were also not different.
      Consistent with these findings, dephosphorylation rates of the 20 kDa myosin
      light chains (MLC(20)), measured in aortic extracts, were nearly identical
      between WT and I-1((-/-)) mice. 4. In the portal vein, I-1 protein ablation was
      associated with a significant (P < 0.05) rightward shift in the EC(50) of
      isoproterenol relaxation (EC(50) = 10.4 +/- 1.4 nM) compared to the WT value
      (EC(50) = 3.5 +/- 0.2 nM). Contraction in response to acetylcholine as well as
      Ca(2+) sensitivity were similar between WT and I-1((-/-)) aorta. 5. Despite the
      prevalence of I-1 and its activation by PKA in the aorta, I-1 does not appear to
      play a significant role in contractile or relaxant responses to any
      pharmacomechanical or electromechanical agonists used. I-1 may play a role as a
      fine-tuning mechanism involved in regulating portal vein responsiveness to beta
      adrenergic agonists.

PMID- 11454957
TI  - Regulation of a G protein-gated inwardly rectifying K+ channel by a Ca(2+)
      independent protein kinase C.
AB  - 1. Members of the Kir3.0 family of inwardly rectifying K(+) channels are
      expressed in neuronal, atrial and endocrine tissues and play key roles in
      generating late inhibitory postsynaptic potentials (IPSPs), slowing heart rate
      and modulating hormone release. They are activated directly by G(betagamma)
      subunits released in response to G(i/o)-coupled receptor stimulation. However, it
      is not clear to what extent this process can be dynamically regulated by other
      cellular signalling systems. In this study we have explored pathways activated by
      the G(q/11)-coupled M(1) and M(3) muscarinic receptors and their role in the
      regulation of Kir3.1+3.2A neuronal-type channels stably expressed in the human
      embryonic kidney cell line HEK293. 2. We describe a novel biphasic pattern of
      behaviour in which currents are initially stimulated but subsequently profoundly
      inhibited through activation of M(1) and M(3) receptors. This contrasts with the
      simple stimulation seen through activation of M(2) and M(4) receptors. 3. Channel
      stimulation via M(1) but not M(3) receptors was sensitive to pertussis toxin
      whereas channel inhibition through both M(1) and M(3) receptors was insensitive.
      In contrast over-expression of the C-terminus of phospholipase Cbeta1 or a
      G(q/11)-specific regulator of G protein signalling (RGS2) essentially abolished
      the inhibitory phase. 4. The inhibitory effects of M(1) and M(3) receptor
      stimulation were mimicked by phorbol esters and a synthetic analogue of
      diacylglycerol but not by the inactive phorbol ester 4alphaphorbol. Inhibition of
      the current by a synthetic analogue of diacylglycerol effectively occluded any
      further inhibition (but not activation) via the M(3) receptor. 5. The receptor
      mediated inhibitory phenomena occur with essentially equal magnitude at all
      intracellular calcium concentrations examined (range, 0-669 nM). 6. The
      expression of endogenous protein kinase C (PKC) isoforms in HEK293 cells was
      examined by immunoblotting, and their translocation in response to phorbol ester
      treatment by cellular extraction. The results indicated the expression and
      translocation of the novel PKC isoforms PKCdelta and PKCepsilon. 7. We also
      demonstrate that activation of such a pathway via both receptor-mediated and
      receptor-independent means profoundly attenuated subsequent channel stimulation
      by G(i/o)-coupled receptors. 8. Our data support a role for a Ca(2+)-independent
      PKC isoform in dynamic channel regulation, such that channel activity can be
      profoundly reduced by M(1) and M(3) muscarinic receptor stimulation.

PMID- 11454958
TI  - Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential
      contribution by two discrete residues.
AB  - 1. The block of the IRK1/Kir2.1 inwardly rectifying K+ channel by a Ba(2+) ion is
      highly voltage dependent, where the ion binds approximately half-way within the
      membrane electrical field. The mechanism by which two distinct mutations, E125N
      and T141A, affect Ba(2+) block of Kir2.1 was investigated using heterologous
      expression in Xenopus oocytes. 2. Analysis of the blocking kinetics showed that
      E125 and T141 affect the entry and binding of Ba(2+) to the channel,
      respectively. Replacing the glutamate at position 125 with an asparagine greatly
      decreased the rate at which the Ba(2+) ions enter and leave the pore. In
      contrast, replacing the polar threonine at position 141 with an alanine affected
      the entry rate of the Ba(2+) ions while leaving the exit rate unchanged. 3.
      Acidification of the extracellular solution slowed the exit rate of the Ba(2+)
      from the wild-type channel, but had no such effect on the Kir2.1(E125N) mutant.
      4. These results thus reveal two unique roles for the amino acids at positions
      125 and 141 in aiding the interaction of Ba(2+) with the channel. Their possible
      roles in K+ permeation are discussed.

PMID- 11454959
TI  - Differential regulation of Ca(2+)-activated Cl(-) currents in rabbit arterial and
      portal vein smooth muscle cells by Ca(2+)-calmodulin-dependent kinase.
AB  - 1. Ca(2+)-activated chloride currents (I(Cl(Ca))) were recorded from smooth
      muscle cells isolated from rabbit pulmonary (PA) and coronary artery (CA) as well
      as rabbit portal vein (PV). The characteristics and regulation by Ca(2+)
      calmodulin-dependent kinase II (CaMKII) were compared between the three cell
      types. 2. In PA and CA myocytes dialysed and superfused with K+ -free media,
      pipette solutions containing fixed levels of free Ca(2+) in the range of 250 nM
      to 1 microM evoked well sustained, outwardly rectifying I(Cl(Ca)) currents in
      about 90 % of cells. The CaMKII inhibitor KN-93 (5 microM) increased the
      amplitude of I(Cl(Ca)) in PA and CA myocytes. However, the threshold
      intracellular Ca(2+) concentration for detecting this effect was different in the
      two arterial cell types. KN-93 also enhanced the rate of activation of the time
      dependent current during depolarising steps, slowed the kinetics of the tail
      current following repolarisation, and induced a negative shift of the steady
      state activation curve. 3. In PA myocytes, the effects of KN-93 were not mirrored
      by its inactive analogue KN-92 but were reproduced by the inclusion of
      autocamtide-2-related CaMKII inhibitory peptide (ARIP) in the pipette solution.
      Cell dialysis with constitutively active CaMKII (30 nM) significantly reduced
      I(Cl(Ca)) evoked by 500 nM Ca(2+). 4. In PV myocytes, I(Cl(Ca)) was evoked by
      pipette solutions containing up to 1 microM free Ca(2+) in less than 40 % of
      cells. Application of KN-93 to cells where I(Cl(Ca)) was sustained produced a
      small inhibition (approximately 25%) of the current in 70 % of the cells. 5. The
      present study shows that regulation of Ca(2+)-dependent Cl(-) channels by CaMKII
      differs between arterial and portal vein myocytes.

PMID- 11454960
TI  - Expression of volume-sensitive Cl(-) channels and ClC-3 in acinar cells isolated
      from the rat lacrimal gland and submandibular salivary gland.
AB  - 1. The expression of ClC-3 was examined in rat lacrimal gland and submandibular
      salivary gland cells using RT-PCR and Western analysis. Whole-cell patch clamp
      methods were used to investigate the expression of volume-sensitive anion
      channels in acinar cells isolated from these tissues. 2. Expression of mRNA
      encoding ClC-3, and ClC-3 protein, was found in rat submandibular gland by RT-PCR
      and Western analysis. Rat lacrimal gland cells, however, did not appear to
      express mRNA encoding for ClC-3, nor the ClC-3 protein. 3. Volume-sensitive anion
      conductances were observed in both rat lacrimal gland and submandibular salivary
      gland acinar cells. The conductance was of a similar size in the two cell types,
      but was much slower to activate in the lacrimal cells. 4. The properties of the
      conductances in lacrimal and submandibular cells were similar, e.g. halide
      selectivity sequence (P(I) > P(Cl) > P(aspartate)) and inhibition by 4,4'
      diisothiocyanostilbene-2,2'-disulphonic acid, 5-nitro-2-(3-phenylpropylamino)
      benzoate and tamoxifen. 5. The data suggest that the expression of ClC-3 is not
      an absolute requirement for the activity of volume-sensitive anion channels in
      rat lacrimal gland acinar cells.

PMID- 11454961
TI  - Ionic selectivity of native ATP-activated (P2X) receptor channels in dissociated
      neurones from rat parasympathetic ganglia.
AB  - 1. The relative permeability of the native P2X receptor channel to monovalent and
      divalent inorganic and organic cations was determined from reversal potential
      measurements of ATP-evoked currents in parasympathetic neurones dissociated from
      rat submandibular ganglia using the dialysed whole-cell patch clamp technique. 2.
      The P2X receptor-channel exhibited weak selectivity among the alkali metals with
      a selectivity sequence of Na(+) > Li(+) > Cs(+) > Rb(+) > K(+), and permeability
      ratios relative to Cs(+) (P(X)/P(Cs)) ranging from 1.11 to 0.86. 3. The
      selectivity for the divalent alkaline earth cations was also weak with the
      sequence Ca(2+) > Sr(2+) > Ba(2+) > Mn(2+) > Mg(2+). ATP-evoked currents were
      strongly inhibited when the extracellular divalent cation concentration was
      increased. 4. The calculated permeability ratios of different ammonium cations
      are higher than those of the alkali metal cations. The permeability sequence
      obtained for the saturated organic cations is inversely correlated with the size
      of the cation. The unsaturated organic cations have a higher permeability than
      that predicted by molecular size. 5. Acidification to pH 6.2 increased the ATP
      induced current amplitude twofold, whereas alkalization to 8.2 and 9.2 markedly
      reduced current amplitude. Cell dialysis with either anti-P2X(2) and/or anti
      P2X(4) but not anti-P2X(1) antibodies attenuated the ATP-evoked current
      amplitude. Taken together, these data are consistent with homomeric and/or
      heteromeric P2X(2) and P2X(4) receptor subtypes expressed in rat submandibular
      neurones. 6. The permeability ratios for the series of monovalent organic
      cations, with the exception of unsaturated cations, were approximately related to
      the ionic size. The relative permeabilities of the monovalent inoganic and
      organic cations tested are similar to those reported previously for cloned rat
      P2X(2) receptors expressed in mammalian cells.

PMID- 11454962
TI  - Selective activation of nociceptors by P2X receptor agonists in normal and
      inflamed rat skin.
AB  - 1. ATP can elicit pain in humans and, together with other P2X channel agonists,
      can produce nocifensive responses in rodents. We used the rat in vitro skin-nerve
      preparation to quantify primary afferent responses to ATP and its stable analogue
      alpha,beta-methylene ATP in normal and carrageenan-inflamed skin. 2. Both ATP and
      alpha,beta-methylene ATP were found to specifically activate the peripheral
      terminals of Adelta and C-fibre nociceptors in the skin. Thirty-nine per cent of
      the nociceptors tested responded to the maximal dose of alpha,beta-methylene ATP
      (5 mM). In contrast, non-nociceptive, low-threshold mechano-sensitive fibres were
      never activated by the same agonist concentrations. 3. Amongst the nociceptor
      population, C-mechanoheat fibres (C-MH or polymodal nociceptors) were markedly
      more responsive to P2X agonists than mechanonociceptors (C-M nociceptors) with
      Adelta- or C-fibre axons. Both C-mechanoheat and C-mechanonociceptors were
      activated by alpha,beta-methylene ATP doses as low as 50 microM. 4. In skin
      inflamed with carrageenan 3-4 h before recording both the number of responsive C
      fibre nociceptors and their response magnitude increased. The increased neural
      response under inflammatory conditions was largely observed in C-mechanoheat or
      polymodal nociceptors. After low doses of P2X agonists C-MH fibres but not C-M
      fibres developed elevated ongoing activity and this effect was only seen after
      carrageenan inflammation. The time course of alpha,beta-methylene ATP-evoked
      discharges in nociceptors was found to correlate well with the time course of
      behavioural nocifensive responses in rats to the same agonist described in a
      previous study (Hamilton et al. 1999). 5. We conclude that the rapid increase in
      the number of alpha,beta-methylene ATP responsive nociceptors and the increased
      magnitude of the neural response following carrageenan inflammation explains why
      very low concentrations of such agonists can cause pain in inflammatory states.

PMID- 11454963
TI  - Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in
      neonatal mice in vitro.
AB  - 1. The effects of substance P (SP), acting at NK1 receptors, on the excitability
      and inspiratory activity of hypoglossal (XII) motoneurons (MNs) were investigated
      using rhythmically active medullary-slice preparations from neonatal mice
      (postnatal day 0-3). 2. Local application of the NK1 agonist [SAR(9),Met
      (O(2))(11)]-SP (SP(NK1)) produced a dose-dependent, spantide- (a non-specific NK
      receptor antagonist) and GR82334-(an NK1 antagonist) sensitive increase in
      inspiratory burst amplitude recorded from XII nerves. 3. Under current clamp,
      SP(NK1) significantly depolarized XII MNs, potentiated repetitive firing
      responses to injected currents and produced a leftward shift in the firing
      frequency-current relationships without affecting slope. 4. Under voltage clamp,
      SP(NK1) evoked an inward current and increased input resistance, but had no
      effect on inspiratory synaptic currents. SP(NK1) currents persisted in the
      presence of TTX, were GR82334 sensitive, were reduced with hyperpolarization and
      reversed near the expected E(K). 5. Effects of the alpha(1)-noradrenergic
      receptor agonist phenylephrine (PE) on repetitive firing behaviour were virtually
      identical to those of SP(NK1). Moreover, SP(NK1) currents were completely
      occluded by PE, suggesting that common intracellular pathways mediate the actions
      of NK1 and alpha(1)-noradrenergic receptors. In spite of the similar actions of
      SP(NK1) and PE on XII MN responses to somally injected current, alpha(1)
      noradrenergic receptor activation potentiated inspiratory synaptic currents and
      was more than twice as effective in potentiating XII nerve inspiratory burst
      amplitude. 6. GR82334 reduced XII nerve inspiratory burst amplitude and generated
      a small outward current in XII MNs. These observations, together with the first
      immunohistochemical evidence in the newborn for SP immunopositive terminals in
      the vicinity of SP(NK1)-sensitive inspiratory XII MNs, support the endogenous
      modulation of XII MN excitability by SP. 7. In contrast to phrenic MNs (Ptak et
      al. 2000), blocking NMDA receptors with AP5 had no effect on the modulation of
      XII nerve activity by SP(NK1). 8. In conclusion, SP(NK1) modulates XII motoneuron
      responses to inspiratory drive primarily through inhibition of a resting,
      postsynaptic K+ leak conductance. The results establish the functional
      significance of SP in controlling upper airway tone during early postnatal life
      and indicate differential modulation of motoneurons controlling airway and pump
      muscles by SP.

PMID- 11454964
TI  - Role of alpha(2)-adrenoceptors in the sympathetic inhibition of motility reflexes
      of guinea-pig ileum.
AB  - 1. Sympathetic regulation of the motility of guinea-pig ileum was investigated
      using mesenteric nerve (MN) stimulation to inhibit motility reflexes, in vitro.
      2. Transmural electrical stimulation (5 Hz, 1 s) in intact intestinal segments,
      or inflation of a balloon against the mucosa in opened segments, evoked
      contractions of the circular and longitudinal muscles oral to the stimulus. 3. MN
      stimulation (10 Hz, 5 s) usually abolished contractions of the longitudinal and
      circular muscles evoked by either electrical or mechanical stimuli. 4. The
      inhibition was mimicked by UK14,304 (70-100 nM) and abolished by idazoxan (100
      nM), revealing an enhancement of circular muscle contractions. There was no
      evidence for alpha(2)-receptors on the muscle, suggesting sympathetic inhibition
      was via the myenteric plexus. 5. Possible sites of action of noradrenaline
      released from sympathetic nerves were investigated using intracellular recordings
      from the circular muscle in a multichambered organ bath. 6. When in the
      stimulation chamber, UK14,304 depressed (by 50 %) excitatory junction potentials
      (EJPs) recorded oral to a distension stimulus, but did not affect inhibitory
      junction potentials (IJPs) recorded anal to the stimulus. When added to a chamber
      between the stimulus and recording chambers, UK14,304 depressed EJPs by 40 %, but
      did not alter IJPs. When in the recording chamber, UK14,304 depressed EJPs by 20
      %, but had no effect on IJPs. IJPs were inhibited, however, when UK14,304 was
      applied to the whole bath. 7. It is concluded that sympathetic activity inhibits
      intestinal motility mainly via alpha(2)-adrenoceptors on ascending interneurons
      and intrinsic sensory neurons of the orally directed reflex pathway.

PMID- 11454965
TI  - In vivo mechanisms of vascular endothelial growth factor-mediated increased
      hydraulic conductivity of Rana capillaries.
AB  - 1. Vascular endothelial growth factor (VEGF) increases hydraulic conductivity
      (L(p)) in vivo. To determine the signal transduction cascade through which this
      is mediated, we measured the effect of inhibition of various signalling pathways
      on VEGF-mediated acute increases in L(p) in individually perfused frog mesenteric
      microvessels. 2. VEGF receptors have previously been shown to activate
      phospholipase C-gamma (PLCgamma), protein kinase C (PKC) and MEK, the mitogen
      activated and extracellular signal-related kinase (ERK) kinase. To determine the
      role of these signalling pathways we measured the effects of inhibitors of each
      on the VEGF-mediated increase in L(p). 3. VEGF-mediated increases in L(p) were
      attenuated by pre-treatment with the PLC inhibitor U73122, but not affected by
      treatment with the inactive enantiomer U73343. The PLC inhibitor was also able to
      attenuate the increase in L(p) mediated by the inflammatory mediator ATP. 4.
      Inhibition of either PKC or MEK activation using the selective inhibitors
      bisindolylmaleimide (BIM, 1 microM) and PD98059 (30 microM), respectively, did
      not change the VEGF-mediated increase in L(p). However, PD98059, BIM and U73122
      all reduced phosphorylation of ERK1/2 determined by Western blot analysis with
      anti-phospho-ERK1/2 antibodies. 5. Furthermore, inhibition of the conversion of
      diacyl glycerol (DAG) to arachidonic acid, by perfusion with the DAG lipase
      inhibitor RHC80267 (50 microM), did not attenuate the increase in L(p) brought
      about by VEGF. 6. These data suggest that VEGF acutely increases microvascular
      permeability in vivo through a mechanism that is dependent on PLC stimulation,
      but is independent of PKC or MEK activation or production of arachidonic acid
      from DAG. We therefore propose that VEGF acutely acts to increase L(p) through
      the direct actions of DAG, independently of PKC or arachidonic acid.

PMID- 11454966
TI  - The dynamic characteristics of the feedback signal from horizontal cells to cones
      in the goldfish retina.
AB  - 1. The dynamic properties of the microcircuitry formed by cones and horizontal
      cells in the isolated goldfish retina were studied. Cones project to horizontal
      cells and horizontal cells feed back to cones via a relatively slow negative
      feedback pathway. 2. The time constant of the feedback signal in cones and of the
      effect this feedback signal had on the responses of second-order neurons was
      determined using whole-cell patch clamp and intracellular recording techniques.
      3. It was found that the feedback signal in cones had a time constant of around
      80 ms, whereas the time constant of the effect this feedback signal had on the
      second-order neurons ranged from 36 to 116 ms. This range of time constants can
      be accounted for by the non-linearity of the Ca(2+) current in the cones. In
      depolarized cones, the feedback-mediated response in second-order neurons had a
      similar time constant to that of the direct light response of the cone, whereas
      in hyperpolarized cones, the time constant of the feedback-mediated response in
      second-order neurons was considerably larger. 4. Further, it was shown that there
      was no delay in the feedback pathway. This is in contrast to what has been
      deduced from the response properties of second-order neurons. In one type of
      horizontal cell, the responses to red light were delayed relative to the
      responses to green light. This delay in the second-order neurons can be accounted
      for by the interaction of the direct light response of the medium-wavelength
      sensitive cones (M-cones) with the feedback response of the M-cones received from
      the horizontal cells.

PMID- 11454967
TI  - Serotonin facilitates AMPA-type responses in isolated siphon motor neurons of
      Aplysia in culture.
AB  - 1. Serotonin (5-HT) facilitates the connections between sensory and motor neurons
      in Aplysia during behavioural sensitization. The effect of 5-HT on sensorimotor
      synapses is believed to be primarily presynaptic. Here we tested whether 5-HT can
      have an exclusively postsynaptic facilitatory effect. 2. Siphon motor neurons
      were individually dissociated from the abdominal ganglion of Aplysia and placed
      into cell culture. Brief pulses of glutamate, the putative sensory neuron
      transmitter, were focally applied (0.1 Hz) to solitary motor neurons in culture,
      and the glutamate-evoked postsynaptic potentials (Glu-PSPs) were recorded. 3.
      When 5-HT was perfused over the motor neuron for 10 min, the amplitude of the Glu
      PSPs was significantly increased. The 5-HT-induced enhancement of the Glu-PSPs
      persisted for at least 40 min after washout. 4. Prior injection into the motor
      neuron of the calcium chelator BAPTA, GDP-beta-S or GTP-gamma-S blocked the 5-HT
      induced facilitation of the Glu-PSPs. However, the facilitation was not blocked
      when APV, an NMDA receptor antagonist, was applied together with the 5-HT. 5. The
      enhancement of the Glu-PSPs by 5-HT was reversed by the AMPA receptor antagonist
      DNQX, indicating that 5-HT increased the functional expression of AMPA-type
      receptors in the motor neuron. 6. The presence of botulinum toxin in the motor
      neuron blocked the 5-HT-induced enhancement of the Glu-PSPs. As botulinum toxin
      prevents exocytosis we hypothesize that during sensitization 5-HT causes the
      insertion of additional AMPA-type receptors into the postsynaptic membrane of
      sensorimotor synapses via exocytosis. This postsynaptic mechanism may contribute
      to facilitation of the synapses.

PMID- 11454968
TI  - Sensory experiences in humans and single-unit activity in cats evoked by
      polymodal stimulation of the cornea.
AB  - 1. The cornea of human subjects and of anaesthetised cats was stimulated with a
      jet of air of controlled flow, temperature and CO(2) concentration delivered by a
      gas aesthesiometer. 2. In humans, the intensity and magnitude of various
      components of the sensory experience (intensity of the sensation, degree of
      irritation, magnitude of burning and stinging pain, magnitude of the cold and
      warm components of the sensation) were measured using separate visual analog
      scales. In anaesthetised cats, the impulse response to the same stimuli was
      recorded from single mechanosensory, polymodal and cold-sensitive corneal fibres
      in the ciliary nerves. 3. Intensity-response curves for mechanical stimulation
      showed that all parameters of the sensation experienced by humans increased with
      the intensity of the stimulus. Mechanical stimuli recruited mainly phasic
      mechanosensory and polymodal afferents in the cat. 4. Acidic stimulation with gas
      mixtures of increasing CO(2) concentration evoked irritation, burning and to a
      lesser extent stinging pain of a magnitude roughly proportional to the intensity
      of the stimulus in humans. CO(2) primarily recruited polymodal afferents and
      weakly excited cold-sensitive fibres in the cat's cornea. 5. Heat stimuli evoked
      in humans a sensation profile similar to CO(2) but accompanied by a warmth
      component. In the cat's cornea, heat excited only polymodal fibres and silenced
      cold-sensitive corneal units. 6. Cold stimuli applied to the human cornea
      elicited a sensation of cooling that became irritant at the lowest temperatures.
      Corneal cold-sensitive fibres of the cat were activated in a manner proportional
      to the temperature drop, while polymodal nociceptor fibres were recruited only by
      the lowest temperatures. Topical menthol (0.2 mM) applied to humans evoked and
      later eliminated cold sensations produced by cold stimuli while the irritation
      sensation caused by low temperature stimuli still persisted. 7. Human subjects
      were able to identify masked mechanical, thermal and chemical stimuli applied to
      the cornea. 8. Irritation and cold sensations can therefore be evoked separately
      from the cornea by selective activation of mechanosensory, polymodal and cold
      corneal sensory afferents. Stimulation with different forms of energy usually
      leads to combined activation and/or inhibition of the different populations of
      sensory afferent fibres, evoking blended sensations that include irritation and
      thermal components in a variable degree.

PMID- 11454969
TI  - Adrenomedullin increases fluid extravasation from the splenic circulation of the
      rat.
AB  - 1. We studied the effect of adrenomedullin (ADM) on fluid efflux from the splenic
      vasculature into extravascular spaces. 2. Splenic arterial infusion of ADM (1, 3
      and 9 ng min(-1); n = 9, 11 and 10, respectively) caused a dose-dependent
      increase in intrasplenic fluid efflux (+0.6 +/- 0.3 (saline) vs. +2.0 +/- 0.3 ml
      min(-1) (9 ng min(-1) ADM), P < 0.05), and in splenic (venous minus arterial)
      haematocrit (+0.8 +/- 0.1 (saline, n = 6) vs. +3.1 +/- 0.3 % (9 ng min(-1) ADM, n
      = 7), P < 0.05). There was no change in splenic weight (0.99 +/- 0.02 (saline, n
      = 6) vs. 0.99 +/- 0.02 g (9 ng min(-1) ADM, n = 7), P > 0.05). 3. There was no
      change in MAP before (97.5 +/- 2.2 mmHg), during (98.4 +/- 3.4 mmHg), or after
      (100.2 +/- 2.2 mmHg) intrasplenic infusion of ADM (9 ng min(-1)) (n = 11, P <
      0.05). 4. ADM (9 ng min(-1)) caused an increase in intrasplenic microvascular
      pressure (11.3 +/- 0.3 (saline, n = 5) vs. 13.0 +/- 0.3 mmHg (9 ng min(-1) ADM, n
      = 6), P < 0.05). 5. ADM (1 x 10(-11) to 1 x 10(-6) M) induced greater
      vasorelaxation of isolated preconstricted splenic resistance arteries than veins
      (maximal relaxation: 60 +/- 0.9 (artery, n = 9) vs. 43 +/- 1.7 % (vein, n = 8), P
      < 0.05). L-NMMA (10(-4) M) partially inhibited the ADM-induced relaxation in
      splenic arteries (maximal relaxation: 38 +/- 3 (ADM + L-NMMA, n = 5) vs. 60 +/- 3
      % (ADM + D-NMMA, n = 5), P < 0.05). 6. It is concluded that ADM increases fluid
      efflux from the splenic vasculature by differentially reducing pre- vs. post
      capillary resistance, thus increasing intrasplenic microvascular pressure.

PMID- 11454970
TI  - Minimal force-frequency modulation of inotropy and relaxation of in situ murine
      heart.
AB  - 1. The normal influence of heart rate (HR) on cardiac contraction and relaxation
      in the mouse remains uncertain despite its importance in interpreting many
      genetically engineered models. Prior in vivo data have repeatedly shown positive
      effects only at subphysiological heart rates, yet depressed basal conditions and
      use of load-dependent parameters probably have an impact on these results. 2.
      Open-chest mice of various strains (n = 16, etomidate/urethane anaesthesia) were
      instrumented with a miniaturized pressure-volume catheter employing absolute left
      ventricular (LV) volume calibration. HR was slowed (< 400 beats min(-1)) using
      ULFS-49, and atrial or ventricular pacing was achieved via an intra-oesophageal
      catheter. Pressure-volume data yielded cardiac-specific contractile indexes
      minimally altered by vascular load. 3. At a resting HR of 600 beats min(-1), peak
      pressure-rise rate (dP/dt(max)) was 16 871 +/- 2941 mmHg s(-1) (mean +/- S.D.)
      and the relaxation time constant was 3.9 +/- 0.8 ms, similar to values in
      conscious animals. Within the broad physiological range (500-850 beats min(-1)),
      load-insensitive contractile indexes and relaxation rate varied minimally,
      whereas dP/dt(max) peaked at 600 +/- 25 beats min(-1) and decreased at higher
      rates due to preload sensitivity. Contraction and relaxation were enhanced
      modestly (13-15 %) at HRs of between 400 and 500 beats min(-1). 4. The minimal
      force-frequency dependence was explained by rapid calcium cycling kinetics, with
      a mechanical restitution time constant of 9 +/- 2.7 ms, and by dominant
      sarcoplasmic reticular buffering (recirculation fraction of 93 +/- 1 %). 5. The
      mouse normally has a very limited force-frequency reserve at physiological HRs,
      unlike larger mammals and man. This is important to consider when studying
      disease evolution and survival of genetic models that alter calcium homeostasis
      and SR function.

PMID- 11454971
TI  - Vagus nerve stimulation decreases left ventricular contractility in vivo in the
      human and pig heart.
AB  - 1. Studies of the effect of vagus nerve stimulation on ventricular myocardial
      function in mammals are limited, particularly in the human. 2. The present study
      was designed to determine the effect of direct electrical stimulation of the left
      vagus nerve on left ventricular contractile state in hearts paced at 10 % above
      the natural rate, in anaesthetised pigs and anaesthetised human subjects
      undergoing open chest surgery for coronary artery bypass grafting. 3.
      Contractility of the left ventricle was determined from a series of pressure
      volume loops obtained from a combined pressure and conductance (volume) catheter
      placed in the left ventricle. From the measurements a regression slope of the end
      systolic pressure-volume relationship was determined to give end-systolic
      elastance (Ees), a load-independent measure of contractility. 4. In six
      anaesthetised open chest pigs, stimulation of the peripheral cut end of the left
      cervical vagus nerve induced a significant decrease in Ees of 26 +/- 14 %. 5. In
      nine patients electrical stimulation of the left thoracic vagus nerve close to
      its cardiac branch resulted in a significant drop in Ees of 38 +/- 16 %. 6. The
      effects of vagal stimulation were blocked by the muscarinic antagonist
      glycopyrronium (5 mg kg(-1)). 7. Administration of the beta-adrenoreceptor
      antagonist esmolol (1 mg kg(-1)) also attenuated the effect of vagal stimulation,
      indicating a degree of interaction of vagal and sympathetic influences on
      contractility. 8. These studies show that in the human and pig heart the left
      vagus nerve can profoundly decrease the inotropic state of the left ventricular
      myocardium independent of its bradycardic effect.

PMID- 11454972
TI  - Synchronous oscillations of length and stiffness during loaded shortening of frog
      muscle fibres.
AB  - 1. A study was made of the damped oscillations in fibre length that are observed
      when isolated muscle fibres from the frog are released during the plateau of an
      isometric tetanus to shorten against a constant load (force clamp recording) near
      the isometric level (temperature, 1.0-11.0 degrees C; initial sarcomere length,
      2.25 microm). 2. The oscillatory length changes of the whole fibre were
      associated with similar length changes of marked consecutive segments along the
      fibre. The segmental length changes were initially in synchrony with the whole
      fibre movements but became gradually more disordered. At the same time the length
      oscillation of the whole fibre was progressively damped. 3. The fast length step
      that normally occurs at the outset of the load-clamp manoeuvre was essential for
      initiating the oscillatory behaviour. Accordingly, no length oscillation occurred
      when the load clamp was arranged to start as soon as the selected tension level
      was reached during the rising phase of the tetanus. 4. The instantaneous
      stiffness was measured as the change in force that occurred in response to a high
      frequency (2-4 kHz) length oscillation of the fibre. During the load-clamp
      manoeuvre, when the tension was kept constant, the stiffness underwent periodic
      changes that correlated well in time with the damped oscillatory changes in fibre
      length. However, there was a phase shift between the stiffness oscillation and
      the oscillation of shortening velocity, the latter being in the lead of the
      stiffness response by 21.4 +/- 0.8 ms (n = 19) at 1.8 +/- 0.1 degrees C. 5. A
      mechanism is proposed to explain the oscillatory behaviour of the muscle fibre
      based on the idea that the quick length step at the outset of the load clamp
      leads to synchronous activity of the myosin cross-bridges along the length of the
      fibre.

PMID- 11454973
TI  - Medullary respiratory neurones and control of laryngeal motoneurones during
      fictive eupnoea and cough in the cat.
AB  - 1. This study addressed the hypothesis that ventrolateral medullary respiratory
      neurones participate in the control of laryngeal motoneurones during both eupnoea
      and coughing. 2. Data were obtained from 28 mid-collicular decerebrated,
      artificially ventilated cats. Cough-like motor patterns (fictive cough) in
      phrenic, lumbar and recurrent laryngeal nerves were elicited by mechanical
      stimulation of the intrathoracic trachea. Microelectrode arrays were used to
      monitor simultaneously several neurones in the ventral respiratory group,
      including the Botzinger and pre-Botzinger complexes. Spike trains were evaluated
      for responses during fictive cough and evidence of functional connectivity with
      spike-triggered averages of efferent recurrent laryngeal nerve activity. 3.
      Primary features were observed in averages triggered by 94 of 332 (28 %)
      neurones. An offset biphasic wave with a positive time lag was present in the
      unrectified average for 10 inspiratory and 13 expiratory neurones. These trigger
      neurones were respectively identified as inspiratory laryngeal motoneurones with
      augmenting, decrementing, plateau and "other" discharge patterns, and expiratory
      laryngeal motoneurones with decrementing firing patterns. 4. Rectified averages
      triggered by inspiratory neurones included 37 offset peaks, 11 central peaks and
      one offset trough. Averages triggered by expiratory neurones had 12 offset peaks,
      six central peaks and four offset troughs. Relationships inferred from these
      features included premotor actions of inspiratory neurones with augmenting,
      decrementing, plateau and "other" patterns on inspiratory laryngeal motoneurones,
      and premotor actions of decrementing and "other" expiratory neurones on
      expiratory laryngeal motoneurones. Corresponding changes in neuronal firing
      patterns during fictive cough supported these inferences. 5. The data confirm and
      extend previous results on the control of laryngeal motoneurones during eupnoea
      and support the hypothesis that the same premotor neurones help to shape
      motoneurone firing patterns during both eupnoea and coughing.

PMID- 11454974
TI  - Changes in respiratory sensations induced by lobeline after human bilateral lung
      transplantation.
AB  - 1. The sensations evoked by the injection of lobeline into the right antecubital
      vein were studied in 8 subjects after bilateral lung transplantation and 10
      control subjects. In control subjects, two distinct sensations were experienced.
      There was an early noxious sensation (onset approximately 10 s) followed by a
      late sensation of breathlessness (onset approximately 26 s) associated with
      involuntary hyperventilation. The early sensation was accompanied by respiratory
      and cardiovascular changes. 2. In contrast to control subjects, the early
      respiratory events and the noxious sensations evoked by injections of lobeline
      (18-60 microg kg(-1)) did not occur in subjects with recent bilateral lung
      transplantation. This suggests that the early respiratory sensations are mediated
      by the discharge of receptors in the lungs. 3. The late hyperventilation and the
      accompanying sensation of breathlessness occurred in both transplant and control
      subjects and are therefore likely to be mediated by receptors elsewhere in the
      body, presumably systemic arterial chemoreceptors stimulated by lobeline. 4. In
      control subjects, but not transplant subjects, there was a consistent decrease in
      mean arterial pressure associated with the lobeline injection. This suggests that
      pulmonary afferents mediate the hypotension. 5. For transplant subjects studied
      more than a year after transplantation, there was some evidence that the noxious
      respiratory sensations evoked by lobeline had returned. This suggests that some
      functional reinnervation of pulmonary afferents may occur.

PMID- 11454975
TI  - Repeated hypoxic exposures change respiratory chemoreflex control in humans.
AB  - 1. A group of seven volunteers (5 male, 2 female) were exposed to 20 min
      isocapnic (eucapnic) hypoxia once daily for 14 consecutive days. Their
      chemoreflexes were measured before and after each exposure. The same volunteers
      repeated the exposures with air substituted for the hypoxic gas mixture in a
      pseudorandom crossover design. 2. On day 1 an initial ventilatory response to
      hypoxia and subsequent decline was discernible in two volunteers, but the mean
      response for all volunteers at this stage was not significant. However, the
      response gradually increased, and by day 14 was discernible in six volunteers
      making the mean response for all volunteers significant. No change was observed
      over the 14 days of air exposure. 3. Only the chemoreflex threshold measured in
      iso-oxic (hypoxic) modified rebreathing tests changed significantly, and only for
      the series of exposures to hypoxia. 4. Over 14 days, the mean +/- S.E.M.
      threshold for all volunteers fell proportionately, from 42 +/- 1.1 mmHg on day 1
      to 39 +/- 1.0 mmHg on day 14. By contrast, the mean +/- S.E.M. threshold, for all
      volunteers and all days, rose from 40 +/- 0.4 mmHg before to 42 +/- 0.5 mmHg
      after the hypoxic exposures. 5. We conclude that the enhancement of the initial
      ventilatory response to hypoxia induced by repeated hypoxic exposure is produced
      by a decrease in chemoreflex threshold. However, the decline in the ventilatory
      response during a single exposure is produced by an increase in the chemoreflex
      threshold. Since threshold changes were only found for hypoxic (iso-oxic)
      modified rebreathing tests, we conclude that only the peripheral chemoreflex
      changed.

PMID- 11454976
TI  - Evidence for metaboreceptor stimulation of sweating in normothermic and heat
      stressed humans.
AB  - 1. Isometric handgrip (IHG) exercise increases sweat rate and arterial blood
      pressure, and both remain elevated during post-exercise ischaemia. The purpose of
      this study was to identify whether the elevation in arterial blood pressure
      during post-exercise ischaemia contributes to the increase in sweating. 2. In
      normothermia and during whole-body heating, 2 min IHG exercise at 40% maximal
      voluntary contraction, followed by 2 min post-exercise ischaemia, was performed
      with and without bolus intravenous administration of sodium nitroprusside during
      the ischaemic period. Sodium nitroprusside was administered to reduce blood
      pressure during post-exercise ischaemia to pre-exercise levels. Sweat rate was
      monitored over two microdialysis membranes placed in the dermal space of forearm
      skin. One membrane was perfused with the acetylcholinesterase inhibitor
      neostigmine, while the other was perfused with the vehicle. 3. In normothermia,
      IHG exercise increased sweat rate at the neostigmine-treated site but not at the
      control site. Sweat rate remained elevated during post-exercise ischaemia even
      after mean arterial blood pressure returned to the pre-IHG exercise baseline.
      Subsequent removal of the ischaemia stimulus returned sweat rate to pre-IHG
      exercise levels. Sweat rate during post-exercise ischaemia without sodium
      nitroprusside administration followed a similar pattern. 4. During whole-body
      heating, IHG exercise increased sweat rate at both neostigmine-treated and
      untreated sites. Similarly, regardless of whether mean arterial blood pressure
      remained elevated or was reduced during post-exercise ischaemia, sweat rate
      remained elevated during the ischaemic period. 5. These results suggest that
      sweating in non-glabrous skin during post-IHG exercise ischaemia is activated by
      metaboreflex stimulation and not via baroreceptor loading.

PMID- 11454977
TI  - A mechanism for increased contractile strength of human pennate muscle in
      response to strength training: changes in muscle architecture.
AB  - 1. In human pennate muscle, changes in anatomical cross-sectional area (CSA) or
      volume caused by training or inactivity may not necessarily reflect the change in
      physiological CSA, and thereby in maximal contractile force, since a simultaneous
      change in muscle fibre pennation angle could also occur. 2. Eleven male subjects
      undertook 14 weeks of heavy-resistance strength training of the lower limb
      muscles. Before and after training anatomical CSA and volume of the human
      quadriceps femoris muscle were assessed by use of magnetic resonance imaging
      (MRI), muscle fibre pennation angle (theta(p)) was measured in the vastus
      lateralis (VL) by use of ultrasonography, and muscle fibre CSA (CSA(fibre)) was
      obtained by needle biopsy sampling in VL. 3. Anatomical muscle CSA and volume
      increased with training from 77.5 +/- 3.0 to 85.0 +/- 2.7 cm(2) and 1676 +/- 63
      to 1841 +/- 57 cm(3), respectively (+/- S.E.M.). Furthermore, VL pennation angle
      increased from 8.0 +/- 0.4 to 10.7 +/- 0.6 deg and CSA(fibre) increased from 3754
      +/- 271 to 4238 +/- 202 microm (2). Isometric quadriceps strength increased from
      282.6 +/- 11.7 to 327.0 +/- 12.4 N m. 4. A positive relationship was observed
      between theta(p) and quadriceps volume prior to training (r = 0.622). Multifactor
      regression analysis revealed a stronger relationship when theta(p) and CSA(fibre)
      were combined (R = 0.728). Post-training increases in CSA(fibre) were related to
      the increase in quadriceps volume (r = 0.749). 5. Myosin heavy chain (MHC)
      isoform distribution (type I and II) remained unaltered with training. 6. VL
      muscle fibre pennation angle was observed to increase in response to resistance
      training. This allowed single muscle fibre CSA and maximal contractile strength
      to increase more (+16 %) than anatomical muscle CSA and volume (+10 %). 7.
      Collectively, the present data suggest that the morphology, architecture and
      contractile capacity of human pennate muscle are interrelated, in vivo. This
      interaction seems to include the specific adaptation responses evoked by
      intensive resistance training.

PMID- 11454979
TI  - Reactivity of germ cell maturation stage-specific markers in spermatocytic
      seminoma: diagnostic and etiological implications.
AB  - It is generally accepted that testicular seminomas and spermatocytic seminomas
      have separate pathogeneses, although the origin of these two types of germ cell
      tumors of the adult testis remains a matter of debate. Although an embryonic germ
      cell origin seems to be most likely for seminomas, a spermatogonia-spermatocyte
      origin has been suggested for spermatocytic seminoma. To shed more light on the
      etiology of spermatocytic seminomas, we undertook an immunohistochemical and
      molecular approach using SCP1 (synaptonemal complex protein 1), SSX (synovial
      sarcoma on X chromosome), and XPA (xeroderma pigmentosum type A) as targets.
      Although a stage-specific expression pattern has been reported for SCP1 and SSX
      in normal spermatogenesis, we demonstrate here that it also exists for XPA. In
      fact, immunohistochemistry shows that the proteins of SCP1 and XPA are
      specifically present in the stage of primary and pachytene spermatocytes. In
      contrast, SSX was found in spermatogonia and primary spermatocytes, as well as in
      germ cells, from at least the 17th week of intrauterine development onward.
      Although no protein encoded by any of these genes was detected in tumor cells of
      a series of testicular seminomas, all tested spermatocytic seminomas were
      positive, in agreement with expression analysis. These data support the model
      that seminomas originate from an embryonic germ cell, and they imply that the
      cell of origin of spermatocytic seminomas is at least capable of maturing to the
      stage of spermatogonia-pachytene spermatocyte.

PMID- 11454980
TI  - Macrophage inflammatory protein-1alpha relates to the recruitment of inflammatory
      cells in myosin-induced autoimmune myocarditis in rats.
AB  - In experimental autoimmune myocarditis (EAM) there is a characteristic initial
      focal inflammatory response in the myocardium, induced mainly by CD4(+) T cells
      and macrophages, which leads to massive myocardial damage. Macrophage
      inflammatory protein-1alpha (MIP-1alpha) induces chemotaxis in lymphocytes,
      eosinophils, basophils, and macrophages. We assessed the potential role of MIP
      1alpha in the pathogenesis of EAM in rats immunized with porcine myosin.
      Following immunization, the levels of MIP-1alpha mRNA in EAM showed an increase
      on Day 11 and peaked on Day 17. MIP-1alpha-positive cells were predominantly
      immunoreactive to OX6 antibody (dendritic cells) and ED2 antibody (resident
      macrophages) by Day 14. Marked cellular infiltration was seen on Day 17 with the
      major population of MIP-1alpha-positive cells also positive for ED1 (inflammatory
      macrophages). We then examined the association of MIP-1alpha with the development
      of myocardial inflammation. Rats were divided into three groups: Group A
      consisted of EAM rats (n = 10); Group B consisted of EAM rats treated with anti
      MIP-1alpha (1 mg/kg) on Days 11, 13, and 15, before the onset of initial
      inflammation (n = 5); and Group C consisted of EAM rats treated with anti-MIP
      1alpha from the start of the initial inflammation on Days 14, 16, and 18 (n = 5).
      Rats were euthanized on Day 21 and three transverse sections of the heart were
      prepared to determine the percentage of the area affected by inflammatory
      lesions. This area of inflammation was significantly smaller in Group B (27 +/-
      4%) than in Groups A (51 +/- 6%) or C (50 +/- 6%) (p < 0.01), indicating that the
      administration of antibody before the initiation of inflammation, in part, will
      inhibit myocardial inflammation. These data suggest that MIP-1alpha may play an
      important role in the recruitment of inflammatory cells in the early stages of
      EAM.

PMID- 11454981
TI  - Sox18 is transiently expressed during angiogenesis in granulation tissue of skin
      wounds with an identical expression pattern to Flk-1 mRNA.
AB  - Sox18 encodes a member of the Sry-related high mobility group box (SOX) family of
      developmental transcription factors. Examination of Sox18 expression during
      embryogenesis has shown that Sox18 is expressed transiently in endothelial cells
      of developing blood vessels, and mutations in Sox18 have been found to underlie
      the mouse vascular and hair follicle mutant ragged. In this study we have
      examined the expression of Sox18 in angiogenesis during wound healing. Full
      thickness skin wounds were created in mice, and subsequent expression of vascular
      endothelial growth factor (VEGF), the VEGF receptor Flk-1, alpha1 (iv) collagen
      (Col4a1), and Sox18 were studied using in situ hybridization. As has been
      previously reported, VEGF was expressed predominantly in the keratinocytes at the
      wound margins. Sox18 expression was found five days after wounding during
      capillary sprouting in granulation tissue and persisted through the proliferative
      phase of healing, but was not detected in fully epithelialized wounds 21 days
      after wounding. Sox18 mRNA expression was detected in capillaries within the
      granulation tissue and showed an identical pattern of distribution to Flk-1 and
      Col4a1 mRNA expression in endothelial cells. Immunostaining with a polyclonal
      anti-Sox18 antibody showed SOX18 protein localized in capillary endothelial cells
      within the granulation tissue. Capillaries in the subcutaneous tissue of
      unwounded skin showed no Sox18 expression. Sox18 may therefore represent a
      transcription factor involved in the induction of angiogenesis during wound
      healing and tissue repair, but not in the maintenance of endothelial cells in
      undamaged tissue.

PMID- 11454983
TI  - Stepwise progression of centrosome defects associated with local tumor growth and
      metastatic process of human pancreatic carcinoma cells transplanted
      orthotopically into nude mice.
AB  - Recent evidence indicates that loss of centrosome integrity may be a major cause
      of genetic instability underlying various human cancers. The aim of this study
      was to define the role of centrosome defects during the in vivo tumor progression
      of pancreatic carcinoma using an orthotopic implantation model. Injection of Suit
      2 human pancreatic cancer cells into the pancreata of nude mice reproduced the
      pattern of local tumor growth and distant metastasis observed in humans.
      Pancreatic xenografts, peritoneal disseminations, and hepatic metastases were
      harvested, and tumor cells were examined for centrosomes by immunofluorescence
      microscopy. Centrosome abnormalities, characterized by increased numbers of
      centrosomes, were detected in only a small fraction of parental Suit-2 cells in
      culture, whereas the frequency was markedly increased in cells isolated from the
      pancreatic xenografts. Abnormal centrosome numbers were found at higher
      frequencies in metastatic foci than in pancreatic xenografts. A significant
      positive correlation existed between the fraction of cells with multiple
      centrosomes and that with multipolar mitotic spindles, suggesting a functional
      involvement of aberrant centrosomes in spindle disorganization and chromosome
      missegregation. In addition, the increased frequency of abnormal centrosomes was
      associated with an enhanced degree of chromosomal instability. These findings
      suggest a novel model of pancreatic tumor progression whereby a stepwise increase
      in the magnitude of centrosomal abnormalities confers an increased chance for
      aberrant mitotic events, thus accelerating genetic instability and causing the
      tumor to progress to a more advanced stage.

PMID- 11454984
TI  - Apolipoprotein E protects against neuropathology induced by a high-fat diet and
      maintains the integrity of the blood-brain barrier during aging.
AB  - SUMMARY: The present study provides evidence that chronic intake of a high-fat
      diet induces a dramatic extravasation of immunoglobulins, indicating alterations
      in blood-brain barrier (BBB) functioning, in the brains of apolipoprotein E
      (apoE)-knockout mice, but not of C57Bl/6 control mice. Using sodium fluorescein
      as a marker for the permeability of the BBB, we found additional support for age
      related disturbances of BBB function in apoE-knockout mice. Behavioral analysis
      of apoE-knockout mice compared with C57Bl/6 mice indicated that they were also
      less efficient in acquiring the spatial Morris water maze task. Furthermore, apoE
      knockout mice are known to develop severe atherosclerosis, which is exacerbated
      with a high-fat diet. We therefore compared the apoE-knockout mice with the apoE3
      Leiden transgenic mice, which are known to develop atherosclerosis. However,
      apoE3-Leiden mice that were kept on a high-fat, high-cholesterol diet and that
      developed atherosclerosis to an extent similar to the apoE-knockout mice, showed
      no signs of BBB disturbances. These results indicate for the first time that apoE
      plays an essential role in the maintenance of the integrity of the BBB during
      aging and that it protects the brain from neuropathology induced by a high-fat
      diet. We therefore hypothesize that the role of apoE in the maintenance of the
      integrity of the BBB may be the mechanism by which apoE affects the progression
      of neurodegeneration, as seen in Alzheimer's disease.

PMID- 11454985
TI  - Biclonality of gastric lymphomas.
AB  - The pathogenesis and clonal evolution of gastric diffuse large B-cell lymphoma
      (DLBCL) and its relationship to extranodal marginal zone B-cell lymphoma (MZBL),
      mucosa-associated lymphoid tissue (MALT) type, are still controversial. The aim
      of this study was to establish the clonality of morphologically distinct areas of
      gastric lymphomas as well as their genetic relationship to each other. Six
      gastric lymphomas, consisting of two MZBL, MALT type, two DLBCL, and two
      "composite" lymphomas were subjected to laser capture microdissection and
      subsequent PCR-based amplification of the immunoglobulin heavy chain gene. One
      DLBCL showed a biclonal pattern of rearranged immunoglobulin heavy chain (IgH)
      genes of two different areas without evidence of a common origin. Two composite
      DLBCL with areas of extranodal MZBL, MALT type, were also biclonal and displayed
      different IgH gene rearrangements in the small-cell and in the large-cell
      components, respectively. Sequencing of the CDR3 region revealed unique VH-N-D
      and D-N-JH junctions, thus corroborating the presence of two genuinely distinct
      tumor clones in each of these three cases. In contrast, the remaining three
      gastric lymphomas (one DLBCL and two MZBL, MALT type) showed IgH gene
      rearrangements in which CDR3 regions were identical in the different tumor areas.
      Our results suggest that gastric DLBCL may be composed of more than one tumor
      cell clone. Further, DLBCL may not necessarily evolve by transformation of a low
      grade lymphoma, but may also originate de novo. An ongoing emergence of new tumor
      clones may considerably hamper molecular diagnosis and follow-up of gastric
      DLBCL.

PMID- 11454986
TI  - Corneodesmosin expression in psoriasis vulgaris differs from normal skin and
      other inflammatory skin disorders.
AB  - SUMMARY: Corneodesmosin (Cdsn) is a late differentiation epidermal glycoprotein
      putatively involved in keratinocyte adhesion. The Cdsn gene lies within the
      susceptibility region on chromosome 6p21.3 (PSORS1) for psoriasis, a common
      chronic disfiguring skin disease. A particular allelic variant of Cdsn has a
      strong association with psoriasis. Therefore, genetically and biologically, Cdsn
      is a possible candidate gene for psoriasis susceptibility. To investigate a
      potential role for Cdsn in psoriasis pathogenesis, protein expression studies
      were performed by quantitative immunohistochemistry on normal skin, psoriatic
      skin (lesional and nonlesional), and other skin disorders using monoclonal
      antibodies (G36-19 and F28-27). In normal and nonlesional skin, Cdsn was
      expressed in stratum corneum and one or two layers of superficial stratum
      granulosum. In lesional psoriasis, there was a significant increase in Cdsn
      expression, which was observed in multiple layers of stratum spinosum and in
      stratum corneum. The expression pattern varied from granular, cytoplasmic
      immunoreactivity to cell surface labeling with weakly immunoreactive cytoplasm.
      In chronic atopic dermatitis, lichen planus, mycosis fungoides, and pityriasis
      rubra pilaris, Cdsn immunoreactivity was confined to stratum corneum and upper
      stratum granulosum with no stratum spinosum immunoreactivity. Immunoelectron
      microscopy of normal and lesional psoriatic skin demonstrated Cdsn release
      concomitant with involucrin incorporation into cell envelopes and completed
      before mature envelope formation. Extracellular release of Cdsn occurred at a
      lower level of the epidermis in psoriasis than normal skin. These protein
      expression studies provide evidence of altered Cdsn expression in psoriasis
      consistent with a role of Cdsn in disease pathogenesis. Further functional and
      genetic studies of Cdsn are justified to determine its role as a potential
      psoriasis-susceptibility factor.

PMID- 11454987
TI  - Loss of Fas (CD95/APO-1) regulatory function is an important step in early MALT
      type lymphoma development.
AB  - Fas (CD95, APO-1) mutations were found in autoimmune diseases and some lymphomas,
      suggesting impairment of Fas-mediated cell death signaling that may cause tumor
      development. Because mucosa-associated lymphoid tissue (MALT)-type lymphoma B
      cells recognize autoantigens and proliferate in response to antigen and T cell
      mediated signals, it is suggestive that autoreactive B cell lymphoma precursor
      cells may have escaped the Fas-mediated checkpoint that normally operates in
      healthy individuals. Using different biochemical, molecular, and functional
      approaches, we analyzed the Fas signaling in malignant B cells from seven MALT
      type lymphomas that were additionally characterized for the t(11;18)(q21;q21) and
      four gastric diffuse large B cell lymphomas (DLBL). All DLBLs and three of seven
      MALT-type lymphomas were resistant to Fas-mediated apoptosis in vitro. Moreover,
      four of five MALT-type lymphomas analyzed and one of three DLBLs analyzed showed
      mutations in Fas mRNA transcripts but no loss of heterozygosity in the Fas
      promotor region. Alternative mechanisms of resistance to apoptosis, such as
      decreased expression of Fas or production of soluble Fas were not operative.
      Therefore, it is suggestive that a subgroup of MALT-type lymphoma B cells,
      irrespective of t(11;18)(q21;q21), escape the censoring Fas pathway by mutating
      and inactivating Fas. This identifies a key regulatory step in early MALT-type
      lymphomagenesis.

PMID- 11454988
TI  - Analysis of the lung pathology and alveolar macrophage function in the acid
      sphingomyelinase--deficient mouse model of Niemann-Pick disease.
AB  - Types A and B Niemann-Pick disease (NPD) are lipid storage diseases caused by the
      deficient activity of the lysosomal enzyme, acid sphingomyelinase (ASM). Type B
      NPD is associated with progressive pulmonary function decline and frequent
      respiratory infections. ASM knock-out (ASMKO) mice are available as a model for
      NPD, but the lung pathology in these mice has not been adequately characterized.
      This study shows that by 10 weeks of age ASMKO mice have a significantly higher
      number of cells in their pulmonary airspaces than normal mice, consisting
      primarily of enlarged and often multinucleated macrophages. These mice also have
      much higher levels of sphingomyelin in their airspaces at 10 weeks of age, and
      both cell numbers and sphingomyelin concentrations remain elevated until 26 weeks
      of age. In these older mice an increased number of neutrophils is also seen. The
      alveolar cell population in the ASMKO mice produces less superoxide when
      stimulated, but this can be corrected by providing recombinant ASM to the culture
      media. Elevated levels of the chemokines macrophage inflammatory protein-2 and
      macrophage inflammatory protein-1alpha were also present in the bronchoalveolar
      lavage fluid of ASMKO mice, and this correlated with increased production of
      these chemokines by cultured macrophages and enhanced immunostaining in situ.
      Also, lung histology showed increased cellularity in the alveolar walls of ASMKO
      mice, but no evidence of fibrosis. Ultrastructural analysis of the lungs showed
      that the ASMKO mice have similar pathologic features to human NPD patients, with
      variable lipid storage evident in type I pneumocytes, endothelial cells, and
      airway ciliated epithelia. The alveolar macrophage, however, was the most
      dramatically affected cell type in both mice and humans. These studies indicate
      that the ASMKO mice can be used as a model to study the lung pathology associated
      with NPD, and demonstrate that the cellular and biochemical analysis of pulmonary
      airspaces may be a useful approach to monitoring disease progression and/or
      treatment.

PMID- 11454989
TI  - Differential effects of caspase-1/interleukin-1beta-converting enzyme on acinar
      cell necrosis and apoptosis in severe acute experimental pancreatitis.
AB  - There is recent experimental evidence that inhibition of caspase-1/interleukin
      1beta converting enzyme (ICE) significantly ameliorates overall severity and
      survival in severe acute experimental pancreatitis. However, little is known
      about the effects of this approach on the dynamics and mechanisms of local acinar
      cell damage, which we aimed to investigate in the present study. Severe acute
      pancreatitis (SAP) was induced by retrograde infusion of 4% sodium taurocholate
      in rats treated with isotonic saline or a highly selective, irreversible
      inhibitor of ICE. After 3, 6, and 24 hours, 3 and 7 days, acinar cell death by
      necrosis and apoptosis, as well as intrapancreatic and systemic interleukin-1beta
      (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) expression, was assessed.
      Treatment with the ICE inhibitor significantly reduced the extent of acinar cell
      necrosis accounting for major parenchymal destruction. In contrast, apoptosis was
      confined to the postacute course of the disease and was closely related to
      tubular complex formation, both remaining unchanged. Whereas intrapancreatic IL
      1beta mRNA expression was highly up-regulated in both treated and untreated
      animals, active IL-1beta protein expression and subsequent neutrophil tissue
      infiltration was dramatically decreased in the ICE-inhibited group. Parallel to
      the onset of enhanced apoptotic acinar cell death and tubular complex formation,
      TNF-alpha mRNA and protein expression was up-regulated, with levels being lower
      in ICE inhibitor-treated rats. We conclude that activation of caspase-1/ICE plays
      a central role in the progression of acinar cell death by necrosis in SAP.
      Herein, IL-1beta-mediated neutrophil infiltration seems to be a crucial step in
      enhanced cellular destruction. In contrast, acinar cell apoptosis contributes to
      ductal transformation and is independent of this mechanism, but may be influenced
      by TNF-alpha.

PMID- 11454990
TI  - Tenascin-C modulates adhesion of cardiomyocytes to extracellular matrix during
      tissue remodeling after myocardial infarction.
AB  - Tenascin-C (TNC), an extracellular matrix glycoprotein, plays important roles in
      tissue remodeling. TNC is not normally expressed in adults but reappears under
      pathologic conditions. The present study was designed to clarify the contribution
      of TNC to ventricular remodeling after myocardial infarction. We examined the
      expression of TNC after experimental myocardial infarction in the rat by
      immunohistochemistry and in situ hybridization. Within 24 hours of permanent
      coronary ligation, interstitial fibroblasts in the border zone started to express
      TNC mRNA. The expression of TNC was down-regulated on Day 7 and was no longer
      apparent by Day 14 after infarction. During the healing process, TNC protein and
      TNC-producing cells were found at the edges of the residual myocardium. Some of
      the TNC-producing cells were immunoreactive for alpha-smooth muscle actin. In
      culture, TNC increased the number of cardiomyocytes attached to laminin but
      inhibited the formation of focal contacts at costameres. The results indicate
      that during the acute phase after myocardial infarction, interstitial cells in
      the border zone synthesize TNC, which may loosen the strong adhesion of surviving
      cardiomyocytes to connective tissue and thereby facilitate tissue reorganization.

PMID- 11454991
TI  - Flt-3 and its ligand are expressed in neural crest-derived tumors and promote
      survival and proliferation of their cell lines.
AB  - Flt-3 ligand (FL) is a cytokine that promotes the survival, proliferation, and
      differentiation of hematopoietic progenitors in synergy with other growth
      factors, such as stem cell factor. Previously we have demonstrated that stem cell
      factor and its receptor c-kit are expressed in neural crest-derived tumor cells
      and that a c-kit block induces their apoptosis. Here we have evaluated the
      expression of flt-3 and its ligand in 12 neuroectodermal tumor cell lines from
      neuroblastoma (NB), neuroepithelioma (NE), Ewing sarcoma (ES), and peripheral
      neuroectodermal tumor (PNET) and in 38 biopsies: 19 from NB and 19 from ES and
      PNET. RT-PCR demonstrated the expression of flt-3 and FL in all lines.
      Coexpression was observed in 42% of NB and in 74% of ES and PNET biopsies. Flow
      cytometry confirmed the presence of membrane and cytoplasmic flt-3 and membrane
      FL in all lines, whereas soluble FL protein was not measurable in their
      supernatants. Microphysiometric demonstration of acidification of the medium
      provided evidence of the specific response of cell lines to FL stimulation.
      Specific flt-3 phosphorylation after FL treatment was also demonstrated by
      Western blotting analysis. In cells growing in RPMI plus 1% fetal calf serum, FL
      revealed a significant proliferating activity, more evident in NB and NE lines
      (mean increase of viable cells, 73 +/- 26% after 1 day). Treatment with flt-3
      antisense oligonucleotides significantly inhibited cell growth. FL also displayed
      an antiapoptotic activity: after a 12-hour culture in the presence of 0.1% fetal
      calf serum, FL caused a 50% reduction of apoptotic cells. These results provide
      further evidence that neuroectodermal and hematopoietic cells share common
      regulatory pathways, and could be of interest in the clinical management of
      neuroectodermal tumors.

PMID- 11454992
TI  - Mapping and genome sequence analysis of chromosome 5 regions involved in bladder
      cancer progression.
AB  - We studied the evolution of allelic losses on chromosome 5 by whole-organ
      histologic and genetic mapping in 234 mucosal DNA samples of 5 cystectomy
      specimens with invasive bladder cancer and preneoplastic changes in adjacent
      urothelium. The frequency of alterations in individual loci was verified on 32
      tumors and 29 voided urine samples from patients with bladder cancer. Finally,
      deleted regions on chromosome 5 were integrated with the human genome contigs and
      sequence-based databases. Deleted regions on chromosome 5 involved in
      intraurothelial phases of bladder neoplasia defined by their nearest flanking
      markers and predicted size were identified as follows: q13.3-q22 (D5S424-D5S656;
      38.8 centimorgan [cM]); q22-q31.1 (D5S656-D5S808; 19.2 cM), q31.1-q32 (D5S816
      SPARC; 11.5 cM), and q34 (GABRA1-D5S415; 6.4 cM). The two most frequently deleted
      neighbor markers (D5S2055 and D5S818) mapping to q22-q31.1 defined a 9 cM region,
      which may contain genes that play an important role in early phases of urinary
      bladder carcinogenesis. Human genome database analysis provided an accurate map
      of deleted regions with positions of 138 known genes and revealed several smaller
      gene-rich areas representing putative targets for further mapping. The strategic
      approach presented here, which combines whole-organ histologic and genetic
      mapping with analysis of the rapidly emerging human genome sequence database,
      facilitates identification of genes potentially involved in early phases of
      bladder carcinogenesis.

PMID- 11454993
TI  - The role of epigenetic modifications in retinoic acid receptor beta2 gene
      expression in human prostate cancers.
AB  - The retinoic acid receptor (RAR) beta gene is a putative tumor suppressor gene on
      chromosome 3p24, where a high incidence of loss of heterozygosity is detected in
      many types of tumors. Retinoic acid suppresses cancer cell growth through binding
      to RARs, especially RARbeta, indicating a critical role in mediating anticancer
      effects. Selective loss or down-regulation of RARbeta mRNA and protein has been
      reported in prostate cancers (PCas), although the mechanisms remain unclear. We
      investigated the role of epigenetic modification in RARbeta2 gene silencing.
      Aberrant methylation was detected in 11 of 14 (79%) primary PCas, 9 of 10 (90%)
      hormone-refractory PCas, and 2 of 4 (50%) PCa cell lines, but not in any normal
      prostate samples. Chromatin immunoprecipitation assay showed that all RARbeta2
      negative cells (LNCaP, PC3, and DU145) were hypoacetylated at both histones H3
      and H4. After exposure to 5-aza-2prime;-deoxycytidine treatment, Trichostatin A
      and all-trans retinoic acid induced partial demethylation, increased accumulation
      of acetylated histones, and markedly restored the expression of RARbeta2 in
      RARbeta2-negative cells. These data suggest that the RARbeta2 gene may be one of
      the frequently silenced genes by epigenetic modifications in PCa.

PMID- 11454994
TI  - Grading of acute and chronic renal lesions in Henoch-Schonlein purpura.
AB  - The renal outcome of 34 patients with Henoch-Schonlein purpura nephritis was
      assessed clinically and by grading acute and chronic renal lesions using a system
      we applied to primary IgA nephropathy. On a median follow-up period of 65 months,
      hypertension and the serum levels of creatinine and proteinuria at the time of
      renal biopsy were correlated with renal survival. Acute glomerular lesions
      including mesangial hypercellularity, endocapillary proliferation, necrosis,
      cellular crescents, and leukocytes infiltration were observed, respectively, in
      41%, 12%, 50%, 29%, and 32% of the cases. Of these, only glomerular necrotizing
      lesion and cellular crescent were correlated with the renal survival. Chronic
      renal lesions based on a grading system applied to primary IgA nephropathy and
      assessing the extent of glomerular sclerosis (glomerular grading), of tubular
      loss and interstitial fibrosis (tubulointerstitial grading), and of hyaline
      arteriolosclerosis demonstrated correlation between these lesions, as well as
      with renal survival. On follow-up, these chronic renal lesions were predictors of
      subsequent clinical events associated with disease progression, such as impaired
      renal function, significant proteinuria, and development of hypertension. Despite
      some limitations related to the relatively small size, this series indicates that
      distinction of acute and chronic lesions of Henoch-Schonlein purpura nephritis is
      important for both the prognosis and management of patients.

PMID- 11454995
TI  - Clinical, histopathological, and immunogenetic analysis of ocular adnexal
      lymphoproliferative disorders: characterization of malt lymphoma and reactive
      lymphoid hyperplasia.
AB  - Malignant lymphomas and reactive lymphoid hyperplasia (RLH) in the ocular adnexa
      are sometimes difficult to differentiate morphologically and have often been
      categorized together as a lymphoproliferative disorder. Immunogenotypic
      characters of these diseases have not yet been well clarified. This study
      included 76 cases of ocular adnexal lymphoproliferative disorders. These
      consisted of 52 cases of malignant lymphoma (43 primary and 9 secondary), 22 of
      RLH, and 2 borderline cases. There were slightly more male than female subjects.
      Diagnoses were based on morphology and immunophenotypic characteristics.
      Clonalities were detected by means of polymerase chain reaction (PCR), and
      immunoglobulin heavy-chain variable region (VH) genes were sequenced in 10 cases
      of mucosa-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma constituted
      86% (37 cases) of the primary lymphomas. MALT lymphomas were more indolent, more
      rarely disseminated, and had a lower death rate than the other primary lymphomas.
      Two patients exhibited coexistence of MALT and diffuse large B-cell lymphoma. The
      average age of patients with RLH was 5.5 years younger than that of those with
      MALT lymphoma. One of the cases of RLH later progressed to malignant lymphoma. B
      cell clonality was detected by PCR in 57%, 55%, and 0% of primary lymphomas, MALT
      lymphomas and RLHs, respectively. Sequencing of VH genes revealed that the VH3
      family was the most commonly expressed germline VH family (70%) and that DP-63,
      DP-54 and DP-47 genes were frequently found in the MALT lymphomas examined. PCR
      analysis was useful for differentiation between MALT lymphoma and RLH. Sequence
      analysis of VH genes showed that an autoimmune mechanism may be involved in the
      lymphomagenesis of ocular adnexal MALT lymphoma.

PMID- 11454996
TI  - The prognostic significance of P-cadherin in infiltrating ductal breast
      carcinoma.
AB  - We have immunohistochemically investigated P-cadherin (P-CD) expression in a
      series of 210 infiltrating ductal carcinomas (IDC) in an attempt to assess the
      biological and prognostic relevance of P-CD in patients harboring IDCs. Although
      only 74/210 (35%) of IDCs expressed P-CD in >5% of tumor cells (P-CD-positive
      carcinomas), categorical analyses revealed that P-CD-positive IDCs were larger
      (26 +/- 21 cm versus 22 +/- 11 cm, P =.0568), of higher histological grade (P
      =.0001), and had more lymph node metastases (P =.0327) than P-CD-negative breast
      carcinomas. In addition, P-CD-positive tumors were negative for estrogen (P
      =.0001) and progesterone receptors (P =.0001) and showed reduced E-cadherin
      expression (P =.0276) more frequently than P-CD-negative tumors. Univariate
      analysis carried out in 171 patients demonstrated that P-CD expression was also
      an indicator of poor prognosis (chi(2) = 8.292, P =.004), extent of lymph node
      metastasis (chi(2) = 20.854, P =.0000), histological grade (chi(2) = 12.908, P
      =.0016), and negative progesterone receptors (chi(2) = 4.116, P =.042). However,
      only histological grade and nodal metastases emerged as independent prognostic
      markers in the multivariate analysis. These results suggest that although P-CD
      expression may be involved in the progression of IDCs, its value as an
      independent prognostic factor remains to be established.

PMID- 11454997
TI  - Proximal-type epithelioid sarcoma: a clinicopathologic study of 20 cases.
AB  - We studied the clinicopathologic and immunohistochemical features of 20 cases of
      proximal-type epithelioid sarcoma to identify prognostic factors. The 20 patients
      ranged in age from 13 to 80 years (mean, 40 y); 12 patients were male and 8 were
      female. The tumors presented as deep soft-tissue or subcutaneous masses on the
      inguinal region in five, the thigh in four, the vulva in three, the axilla in
      three, and one each in the flank, chest wall, back, hip and perineum. The tumors
      ranged from 2 to 16 cm at their greatest diameter (mean: 7.8 cm). Histologically,
      12 tumors (60%) were classified as the large-cell subtype, characterized by
      sheets of large cells with prominent nucleoli resembling poorly differentiated
      carcinoma, and a frequent rhabdoid phenotype, six (30%) were classified as the
      conventional subtype, and two (10%) as the angiomatoid subtype. The numbers of
      tumors exhibiting immunoreactivity for various markers were: vimentin (20
      cytokeratin (20 [100%]); epithelial membrane antigen (17 [85%]); CD34 (9 [45%]);
      CD99 (5 [25%]); muscle markers, either desmin or alpha-smooth muscle actin (3
      [15%]), other markers such as S-100 protein, neurofilament, neuron-specific
      enolase, synaptophysin and CD56 (12 [60%]); and p53 (16 [80%]). Fourteen lesions
      (70%) exhibited an MIB-1 index of 30% or more and, by a system of histologic
      grading using the MIB-1 score, 16 tumors (80%) were classified as high-grade
      (Grade 3). Thirteen patients (65%) developed local recurrence and 15 (75%) had
      metastases, primarily to the lymph nodes. At the last follow-up, 13 patients
      (65%) had died of their disease. A large tumor size and early metastasis were
      independently associated with a poor outcome. We conclude that proximal-type
      epithelioid sarcomas are rare, undifferentiated soft-tissue sarcomas of adults,
      with epithelioid features and a frequent rhabdoid phenotype. These tumors, when
      arising in proximal locations, have a much worse prognosis than those arising in
      distal locations.

PMID- 11454998
TI  - Gelatinous ascites: a cytohistologic study of pseudomyxoma peritonei in 67
      patients.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare condition characterized by
      gelatinous ascites. Although the histologic attributes of PMP have been well
      studied, the cytologic features remain ill defined. METHODS: We reviewed the
      peritoneal washings (PW) in 67 patients with PMP to identify cytomorphologic
      features useful in classifying cases as either disseminated peritoneal
      adenomucinosis (DPAM) or peritoneal mucinous carcinomatosis (PMCA). Histologic
      specimens were correlated with the cytologic diagnoses. Correlation between
      cytologic diagnosis and patient outcome was investigated. RESULTS: Neoplastic
      epithelial cells were identified in 63 of 67 PW (94%). Concordance with the
      histologic diagnosis was obtained in 61 of 63 cases. Of these 36.5% were
      cytologically classified as DPAM with primary appendiceal neoplasms in 19 cases.
      Thirty-four of 63 cases (53.9%) were cytologically diagnosed as PMCA based on PW
      cytology. Most were of appendiceal or colonic origin. Four cases displayed
      cytologic features of both DPAM and PMCA. Two discordant cases each with a
      cytologic diagnosis of PMCA had an appendiceal adenoma. Acellular mucin alone was
      identified in the PW in four cases. Analysis of follow-up data revealed that
      cases diagnosed as DPAM had a better prognosis than those diagnosed as PMCA.
      CONCLUSIONS: Cytomorphologic features of epithelial cells in PW material can
      accurately categorize cases of PMP as either DPAM or PMCA. Furthermore, this
      categorization appears to have important prognostic implications.

PMID- 11454999
TI  - Loss of expression of the PTEN gene protein product is associated with poor
      outcome in breast cancer.
AB  - INTRODUCTION: The PTEN gene, a candidate tumor suppressor, is localized to
      chromosome 10q23 and shares extensive homology with cytoskeletal proteins auxilin
      and tensin. A high frequency of mutations at the PTEN locus has been described in
      a variety of neoplasms including breast cancer. However, the role of PTEN
      alternations and its association with outcome variables in breast neoplasia is
      not well established. DESIGN: Formalin-fixed paraffin embedded tissues from 151
      women (mean age 62 years, range 26-98) with primary diagnosis of invasive breast
      cancer were evaluated for PTEN protein expression by automated
      immunohistochemical methods. Slides were scored semi-quantitatively based on
      staining intensity and distribution, and results were compared with clinical
      pathologic parameters. The mean follow-up was 56 months (range 1-169). RESULTS:
      Seventy-three (48%) of 151 breast tumors had loss of PTEN protein expression. On
      univariate analysis, loss of PTEN expression (P =.034), stage (P <.0001), node
      positive (P <.0001), and tumor grade (P =.002) were associated with disease
      related death. Loss of PTEN expression also predicted lymph node metastasis (P
      <.0001), and correlated with loss of estrogen receptor staining (P =.040). Loss
      of PTEN did not correlate with stage, tumor grade, disease recurrence, or loss of
      progesterone receptor [although a trend was seen (P =.092). On multivariate
      analysis, stage (P <.0001), lymph node metastasis (P <.0001), and tumor grade (P
      =.002) correlated with survival. CONCLUSION: Loss of PTEN protein expression
      occurs commonly in breast cancer and correlates with disease related death, lymph
      node metastasis, and loss of estrogen receptor staining. Our results support the
      proposed role of PTEN as a candidate tumor suppressor in breast cancer and
      suggest a need for further study of this marker.

PMID- 11455000
TI  - Defining a test for HER-2/neu evaluation in breast cancer in the diagnostic
      setting.
AB  - In breast cancer amplification of the HER-2/neu oncogene and over-expression of
      the protein product is associated with poor prognosis, predicts response to some
      chemotherapeutic regimens and is the target for Herceptin treatment. To date
      there are several methods to assess the amplification/over-expression of HER
      2/neu with each having advantages and disadvantages. We have studied
      amplification and over-expression of HER-2/neu in 250 consecutive cases of breast
      cancer (220 invasive and 30 in situ carcinomas) presenting to the Department of
      Pathology at Women's College Campus of Sunnybrook and Women's College Health
      Sciences Center. Thirty percent of the invasive carcinomas were node positive.
      HER-2/neu protein over-expression was assessed by immunohistochemistry (IH) using
      antibody CB11 and amplification of the gene by differential PCR. The percentage
      of tumor cells showing CB11 staining was determined and the most significant cut
      off point for positivity was > or =10% moderate or strong complete membranous
      staining. The gene was considered amplified if the density score of the product
      was > or =2. There was 94% concordance between the two methods (P value.0001).
      Both methods were positive in 16% of cases and negative in 78% of cases.
      Discrepant cases were examined by FISH which confirmed the IH results in 9/11
      invasive carcinomas. These results show that there is excellent concordance
      between IH and PCR. However, immunohistochemistry is easier to perform and
      cheaper than PCR and could be used in routine assessment of HER-2/neu in breast
      cancer patients.

PMID- 11455001
TI  - Analysis of MUM1/IRF4 protein expression using tissue microarrays and
      immunohistochemistry.
AB  - The gene encoding MUM1 was characterized as a possible translocation partner in
      chromosomal abnormalities involving a significant number of multiple myelomas.
      The overexpression of the MUM1 protein as a result of translocation t(6;14)
      (p25;q32) identified MUM1 as a putative regulatory molecule involved in B-cell
      differentiation and tumorigenesis. The expression of MUM1 protein in multiple
      myelomas supports this hypothesis. In the current study, using tissue microarray
      technology, we have tested the expression of the MUM1 protein in 1335 human
      malignancies and normal tissues. Our data show that the MUM1 protein is expressed
      in a wide spectrum of hematolymphoid neoplasms and in malignant melanomas but is
      absent in other human tumors. In addition, in tissue microarrays as well as in
      conventional paraffin sections, MUM1 staining was found to lack specificity in
      detecting plasmacytic differentiation as compared with two markers,
      CD138/Syndecan and VS38, commonly used in paraffin immunohistochemistry for
      detection of plasma cells.

PMID- 11455002
TI  - Superficial fibromatoses are genetically distinct from deep fibromatoses.
AB  - Whereas deep fibromatoses (abdominal, extra-abdominal, mesenteric) display
      locally aggressive behavior, superficial fibromatoses typically remain small and
      less likely to recur despite essentially identical morphology. Somatic beta
      catenin or APC gene mutations have been reported in < or =74% of sporadic deep
      fibromatoses and in virtually 100% of Gardner syndrome-associated fibromatoses,
      whereas genetic events in superficial fibromatoses remain less well
      characterized. We performed immunohistochemical staining for beta-catenin on 29
      superficial fibromatoses (22 palmar, 5 plantar, 1 penile, and 1 infantile digital
      fibromatosis) and 5 deep fibromatoses. Mutations of beta-catenin and APC genes
      were analyzed in cases of superficial fibromatoses by direct DNA sequencing of
      the beta-catenin gene on Exon 3 encompassing the GSK-3 36 phosphorylation region
      and of the APC gene on the mutation cluster region. Nuclear accumulation of beta
      catenin was present in 86% (25/29) of superficial fibromatosis cases ranging from
      5 to 100% of nuclei (mean, 13%; median, 10%), though in a minority of nuclei in
      most examples. Deep fibromatoses had 60 to 100% nuclear staining in all five
      cases. No somatic mutations of beta-catenin or APC genes were identified in any
      of the superficial fibromatoses. In contrast to deep fibromatoses, superficial
      fibromatoses lack beta-catenin and APC gene mutations; the significance of focal
      nuclear beta-catenin accumulation is unclear. This difference may account inpart
      for their divergent clinical manifestations despite their morphologic resemblance
      to deep fibromatoses.

PMID- 11455003
TI  - Signal-amplified colorimetric in situ hybridization for assessment of human
      papillomavirus infection in cervical lesions.
AB  - Detection and typing of human papillomavirus (HPV) infection may have a major
      impact in cervical-screening and follow-up. In this study various commercially
      available techniques for the detection of HPV were evaluated. HPV-status was
      determined in 86 samples of cervical cancer by PCR and direct sequencing,
      catalyzed signal amplified colorimetric DNA in situ hybridization (CSAC- ISH)
      (GenPoint system, DAKO), immunohistochemistry (IHC) and in 12 selected cases also
      by conventional, non-amplified ISH. Twenty-one samples of cervical
      intraepithelial neoplasias grade III (CIN III) were investigated by CSAC-ISH,
      conventional ISH and by IHC, in corresponding PAP smears HPV-detection and typing
      was performed by CSAC-ISH and Hybrid Capture test II (HC). In additional 20 PAP
      smears HPV typing was performed using HC and a novel immunocytochemical system
      for HPV detection and-typing. CSAC-ISH showed good correlation with PCR analysis
      in cervical cancers: In 87% of PCR positive cases, HPV infection was also
      detected by CSAC- ISH (66/76). HPV 16 was detected in 75% of PCR-positive cases
      (44/59), HPV 18 in 71% of PCR positive cases (5/7). CSAC-ISH detected HPV 31 in
      only 29% of PCR positive cases (2/7), and HPV 33 in 64% of PCR-positive cases
      (23/36). Nevertheless, CSAC-ISH- false negative cases for HPV 31 or 33 were
      nearly always combined infections with other HPV types, which were detectable by
      CSAC-ISH in most cases. CSAC-ISH revealed HPV infection in 20 of 21 HC-positive
      cervical smears, while in corresponding biopsies (CIN III) CSAC-ISH detected 100%
      of HPV infections. Conventional, non-amplified ISH showed significantly lower
      sensitivity compared with CSAC-ISH, and immunocyto- and -histochemistry were of
      very low sensitivity for detection of HPV. CSAC-ISH is an easy-to-handle method
      for detection and typing of cervical HPV infection, and shows sufficient
      sensitivity for clinical practice.

PMID- 11455004
TI  - Simultaneous paired analysis of numerical chromosomal aberrations and DNA content
      in osteosarcoma.
AB  - Relatively little is known about the biologic relevance of numerical chromosomal
      changes in relation to DNA content in osteosarcoma. In this study, by using a
      series of human osteosarcoma cell lines, we standardized a method for the
      assessment, on the same nuclei specimen, of both specific chromosome copy numbers
      by fluorescence in situ hybridization (FISH) and the DNA content by static
      cytofluorometry or image cytometry. On the same cell lines, we also evaluated the
      DNA content by using flow cytometry and the chromosome number distribution by
      metaphase analysis. Comparison between these different methods showed that DNA
      ploidy level as determined by FISH or metaphase analysis is frequently lower than
      the ploidy pattern as defined by cytometric methods. By using comparative genomic
      hybridization, we were able to demonstrate that these discrepancies were due to
      the presence of several unbalanced chromosome aberrations, specifically gains and
      high-level amplifications, which affect the total DNA content with less effect on
      the total chromosome number. Thus, evaluation of DNA ploidy in osteosarcoma cells
      is needed for a correct interpretation of FISH or cytogenetic data concerning
      numerical chromosomal changes. Evaluation of tumor ploidy in a series of clinical
      samples demonstrated that in high-grade osteosarcoma, flow cytometry sometimes
      may give false results because of the presence of high proportions of
      contaminating, nonneoplastic cells that cannot be excluded from the flow
      cytometric assessment but that do not interfere with the evaluation of DNA ploidy
      by static cytofluorometry or image cytometry, in which only tumor cells are
      selected for the analysis. The possibility of using this method to evaluate, on
      the same nuclei sample, both specific chromosomal aberrations and DNA ploidy may
      allow a better determination of numerical chromosomal changes that may be
      relevant for the biologic behavior of osteosarcoma.

PMID- 11455005
TI  - Diffuse calcification of the airways.
AB  - Airway calcification is usually restricted to the cartilaginous conducting
      portion of the bronchial tree. Alternatively, calcification of the alveoli is a
      relatively common consequence of calcium and phosphate imbalance. We wish to
      report an unusual case in which diffuse calcification of the entire bronchial
      tree, absent alveolar calcification, was identified in a patient with renal
      dysfunction. Pathologists should not exclude metastatic calcification when
      considering the etiology of bronchial calcification.

PMID- 11455006
TI  - Mixed conventional and desmoplastic infantile ganglioglioma: an autopsied case
      with 6-year follow-up.
AB  - We describe a case of desmoplastic infantile ganglioglioma (DIG) arising in the
      ventral diencephalon of a 3-1/2-month-old boy. On biopsy, the tumor featured a
      desmoplastic, S-100 protein and GFAP immunoreactive stromal element, as well as a
      variable spectrum of ganglion cells. Electron microscopy demonstrated astrocytes,
      and morphologically fibroblasts, as well as neurons containing 120-nm dense core
      granules. In addition, tubular structures composed of tightly apposed cells with
      features of astrocytes and of Schwann-like cells were also noted. Devoid of
      fibroblasts, the tubular structures were surrounded by a single basal lamina. At
      autopsy 6 years later, the multinodular, cystic mass had replaced the
      diencephalon, extended into both temporal lobes as well as the optic nerves, and
      showed marked leptomeningeal involvement. Microscopically, superficial portions
      of the tumor consisted of typical DIG, whereas deep, nondesmoplastic portions
      exhibited pattern variation ranging from pilocytic astrocytoma to ganglioglioma
      and gangliocytoma. There was also a minor element of small, 'primitive-appearing'
      neuroepithelial cells. Dysplastic ganglion cells variously reactive for
      neurofilament protein and synaptophysin were present throughout the tumor. Our
      study not only confirms DIG as a variant of ganglioglioma, one capable of slow
      growth, infiltration, and fatal progression but suggests that its differentiating
      potential includes elements of both the central and peripheral nervous systems.
      If so, their derivation may be from multipotential cells of the neural plate.

PMID- 11455007
TI  - Endolymphatic sac tumor associated with a von Hippel-Lindau disease patient: an
      immunohistochemical study.
AB  - The authors report a case of endolymphatic sac tumor (ELST) associated with Von
      Hippel-Lindau disease (VHL). A 20-year-old female VHL patient received a
      resection of a cerebellar hemangioblastoma 3 years ago and she had a co-existing
      of left petrous tumor. The petrous tumor showed a remarkable progression in 3
      years and was resected subtotally. Histologically, the resected petrous tumor
      showed a papillary structure containing cuboidal or columnar cells with fibrous
      stroma and numerous microvessels and destructed temporal bone, all of which are
      consistent with ELST. We studied the expression of various kinds of cytokeratins
      (CKs) immunohistochemically and found distinct expression of CKs (CAM 5.2,
      34betaE-12, CK7, CK8 and CK19), but not for CK10/13 or CK20. Vascular endothelial
      growth factor and neuron specific enolase showed strong immunoreactivity in the
      tumor cells. CD34 also had weak expression. Ki-67 antigen (MIB-1)
      immunoreactivity was found in focal areas, and the labeling index in the highest
      density area was 48.9%. These findings suggest that vascular endothelial growth
      factor overexpression is an important factor for angiogenesis in ELST, much like
      other VHL-associated tumors, and that ELST may have a more highly aggressive
      component than the low-grade malignancy noted in previous reports.

PMID- 11455008
TI  - Re: O'Sullivan MJ, Kyriakos M, Zhu X, Wick MR, Swanson PE, Dehner LP, Humphrey
      PA, Pfeifer JD: malignant peripheral nerve sheath tumors with t(X;18). A
      pathologic and molecular genetic study. Mod pathol 2000;13:1336-46.

PMID- 11455009
TI  - The noncompetitive inhibitor quinacrine modifies the desensitization kinetics of
      muscle acetylcholine receptors.
AB  - Quinacrine has been shown to act as a noncompetitive inhibitor of the nicotinic
      acetylcholine receptor (nAChR). However, its mechanism of action is still a
      matter of controversy. We analyzed in detail the action of quinacrine at both the
      single-channel and macroscopic current levels. The main effect of quinacrine is a
      profound concentration-dependent decrease in both the frequency of opening events
      and the duration of clusters elicited by high acetylcholine concentrations.
      Quinacrine also significantly increases (40-fold at 30 microM) the decay rate of
      macroscopic currents elicited by rapid perfusion of acetylcholine to outside-out
      patches. This decay is still well-described by a single exponential. Quinacrine
      has very little effect on the peak amplitude of the response, suggesting that it
      acts mainly on open channels. The recovery from desensitization after removal of
      acetylcholine is delayed in the presence of quinacrine. Results from both single
      channel and macroscopic current recordings indicate that quinacrine increases the
      rate of nAChR desensitization and stabilizes the desensitized state.
      Interestingly, in equilibrium agonist-binding assays, quinacrine does not promote
      the typical high-affinity desensitized state. Thus, quinacrine seems to induce an
      intermediate state exhibiting the permeability but not the agonist binding
      properties of desensitization.

PMID- 11455010
TI  - Open channel block of HERG K(+) channels by vesnarinone.
AB  - Vesnarinone, a cardiotonic agent, blocks I(Kr) and, unlike other I(Kr) blockers,
      produces a frequency-dependent prolongation of action potential duration (APD).
      To elucidate the mechanisms, we studied the effects of vesnarinone on HERG, the
      cloned human I(Kr) channel, heterologously expressed in Xenopus laevis oocytes.
      Vesnarinone caused a concentration-dependent inhibition of HERG currents with an
      IC(50) value of 17.7 +/- 2.5 microM at 0 mV (n = 6). When HERG was coexpressed
      with the beta-subunit MiRP1, a similar potency for block was measured (IC(50):
      15.0 +/- 3.0 microM at 0 mV, n = 5). Tonic block of the HERG channel current was
      minimal (<5% at 30 microM, n = 5). The rate of onset of block and the steady
      state value for block of current were not significantly different for test
      potentials ranging from -40 to +40 mV [time constant (tau) = 372 +/- 76 ms at +40
      mV, n = 4]. Recovery from block at -60, -90, and -120 mV was not significantly
      different (tau = 8.5 +/- 1.5 s at -90 mV, n = 4). Vesnarinone produced similar
      effects on inactivation-removed mutant (G628C/S631C) HERG channels. The IC(50)
      value was 10.7 +/- 3.7 microM at 0 mV (n = 5), and the onset and recovery from
      block of current findings were similar to those of wild-type HERG. Amino acids
      important for the binding of vesnarinone were identified using alanine-scanning
      mutagenesis of residues believed to line the inner cavity of the HERG channel.
      Six important residues were identified, including G648, F656, and V659 located in
      the S6 domain and T623, S624, and V625 located at the base of the pore helix.
      These residues are similar but not identical to those determined previously for
      MK-499, an antiarrhythmic drug. In conclusion, vesnarinone preferentially blocks
      open HERG channels, with little effect on channels in the rested or inactivated
      state. These actions may contribute to the favorable frequency-dependent
      prolongation in APD.

PMID- 11455011
TI  - Transmembrane domain (TM) 9 represents a novel site in P-glycoprotein that
      affects drug resistance and cooperates with TM6 to mediate
      [125I]iodoarylazidoprazosin labeling.
AB  - The multidrug resistant cell line DC-3F/ADII was obtained by stepwise selection
      for growth in actinomycin D (ActD). Compared with parental cells, it displays
      high resistance to ActD and vincristine and low resistance to colchicine and
      daunorubicin. These cells overexpress a form of P-glycoprotein (Pgp1) containing
      a double mutation, I837L and N839I, in transmembrane domain (TM) 9; when
      transfected into DC-3F, this mutation confers the DC-3F/ADII phenotype. We have
      shown previously that another cell line, DC-3F/ADX, also displays this phenotype
      and overexpresses a mutant form of Pgp1 containing a double mutation in TM6
      (G338A, A339P). Hence, mutations in TM9 and TM6 are independently capable of
      conferring the same cross-resistance phenotype. The TM6 mutations inhibit the
      ability of cyclosporin A to reverse cross-resistance and to block labeling of the
      protein by [125I]iodoarylazidoprazosin (IAAP), whereas the TM9 mutations do not
      show similar effects. A chimeric protein containing both pairs of mutations
      confers twice the level of resistance to ActD than expected from the sum of the
      individual mutations, but it cannot be labeled to detectable levels with
      [125I]IAAP. Thus, TM9 represents a novel site that cooperates with TM6 to mediate
      drug resistance and [125I]IAAP labeling.

PMID- 11455012
TI  - Bystander effects of cancer cell lines transduced with the multisubstrate
      deoxyribonucleoside kinase of Drosophila melanogaster and synergistic enhancement
      by hydroxyurea.
AB  - The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK)
      can be expressed in human cells with retained enzymatic activity. The cells
      expressing Dm-dNK exhibit increased sensitivity to several cytotoxic nucleoside
      analogs. In this study, we further evaluated Dm-dNK as a potential novel suicide
      gene in combination with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) as the
      prodrug. We used two human cancer cell lines transduced with a retrovirus
      encoding the Dm-dNK cDNA and investigated whether the cells expressing the enzyme
      can induce cell death of untransduced cells, a phenomenon known as the "bystander
      effect". A bystander effect was observed in a thymidine kinase-deficient human
      osteosarcoma cell line but not in the MIA PaCa-2 human pancreatic adenocarcinoma
      cell line. The cytotoxicity of BVDU increased in both cell lines when the
      compound was used in combination with subtoxic concentrations of hydroxyurea.
      Hydroxyurea also enhanced the bystander effect in the osteosarcoma cells, but not
      in the MIA PaCa-2 cells, treated with BVDU. These findings indicate that BVDU
      phosphorylated by Dm-dNK in transduced cancer cells may also induce bystander
      cell death in certain cell lines.

PMID- 11455013
TI  - Stimulation of leukotriene synthesis in intact polymorphonuclear cells by the 5
      lipoxygenase inhibitor 3-oxo-tirucallic acid.
AB  - Commercially available extracts from Boswellia serrata resin used as anti
      inflammatory drugs or phytonutrients show paradoxical concentration-dependent
      potentiating and inhibitory actions on 5-lipoxygenase (5-LO) product synthesis in
      stimulated PMNs. In our attempt to characterize the stimulating constituents, we
      identified the tetracyclic triterpene 3-oxo-tirucallic acid (3-oxo-TA), which, in
      the range from 2.5 to 15 microM, enhanced 5-LO product formation in ionophore
      challenged polymorphonuclear cells (PMNs) (e.g., from 1981 +/- 177 to 3042 +/-
      208 pmol at 10 microM 3-oxo-TA), and initiated Ca(2+) mobilization, MEK-1/2
      phosphorylation, 5-LO translocation, and 5-LO product formation in resting cells
      (534 +/- 394 pmol/5 x 10(6) PMNs). In cell-free 5-LO assays, 3-oxo-TA acted only
      inhibitory (IC(50) value of about 3 microM), demonstrating the pivotal role of
      intact cell structure for its activating property. In 3-oxo-TA-challenged PMNs,
      the mitogen-activated protein kinase kinase (MEK)-1/2 inhibitor PD098059
      abolished 5-LO product formation, along with inhibition of MEK-1/2
      phosphorylation and 5-LO translocation. The 3-acetoxy derivative of 3-oxo-TA
      acted like 3-oxo-TA in intact PMNs, whereas 3-hydroxy-TA barely stimulated MEK
      phosphorylation in resting cells and showed only inhibition on ionophore-induced
      5-LO product synthesis. Steroid-type tetracycles neither induced 5-LO activation
      nor had enhancing or inhibitory effects. In summary, defined natural tetracyclic
      triterpenes, which act as inhibitors of the 5-LO in the cell-free assay, initiate
      5-LO activation by a MEK-inhibitor sensitive mechanism and potentiate stimulated
      product synthesis in intact cells. Because TAs contribute significantly to the
      overall biological effects of B. serrata resin extracts, special precaution for
      standardization is recommended when using B. serrata preparations as drugs or
      dietary supplements.

PMID- 11455014
TI  - The antiglucocorticoid RU486 inhibits phenobarbital induction of the chicken
      CYP2H1 gene in primary hepatocytes.
AB  - The cytochrome P450 gene CYP2H1 is highly induced by phenobarbital in chick
      embryo hepatocytes. Recent studies have established that the orphan nuclear
      receptor CAR plays a critical role in the induction mechanism. Here, we show that
      a high concentration of the potent glucocorticoid and progesterone receptor
      antagonist RU486 almost completely blocks phenobarbital-induced accumulation of
      CYP2H1 mRNA in hepatocytes yet has no effect on basal expression. In marked
      contrast, CYP2H1 mRNA induced by the phenobarbital-type inducers glutethimide and
      2-allylisopropylacetamide is not affected by RU486. RU486 inhibition is not
      mediated through the glucocorticoid or progesterone receptors. Transient
      transfection studies showed that RU486 does not repress through activation of the
      orphan receptor PXR and subsequent competition with CAR for binding to the
      upstream drug-responsive 556-base-pair enhancer. Additionally, none of the known
      functional transcription factor binding sites found in the enhancer region was a
      target of RU486 inhibition. Using an artificial construct containing multiple CAR
      binding sites, we also established that RU486 has no direct effect on the
      activity of exogenously expressed CAR. There is no evidence that phenobarbital
      binds to CAR; we propose that RU486 inhibits phenobarbital induction, either by
      interfering with a phenobarbital-dependent mechanism responsible for nuclear
      import of CAR or with the metabolism of phenobarbital to the true inducer.
      Whether a novel nuclear receptor that binds RU486 at high concentrations plays a
      role in the inhibitory action of RU486 is an interesting possibility.

PMID- 11455015
TI  - G protein-gated inwardly rectifying potassium channels are targets for volatile
      anesthetics.
AB  - G protein-gated inwardly rectifying potassium channels (GIRKs) are a family of
      homo- and hetero-oligomeric K(+) channels composed of different subunits (GIRK1
      to 4 in mammals). GIRK4 and GIRK1 are found mainly in the atrium, whereas
      neuronal cells predominantly express the GIRK1, GIRK2, and GIRK3 isoforms. When
      activated, GIRK channels slow the firing rate of atrial myocytes and neuronal
      cells. Because of their key role in controlling excitability, we investigated the
      influence of a prototypic anesthetic, halothane, on GIRK channels of different
      subunit composition expressed in Xenopus laevis oocytes. Halothane enhanced
      background currents through hetero-oligomeric GIRK1/GIRK4 and homo-oligomeric
      GIRK1(F137S) channels but not through homo-oligomeric GIRK2 channels. This
      activation of basal current did not depend on the presence of coexpressed G
      protein-coupled receptors but instead required the presence of G(beta/gamma). In
      contrast to basal GIRK currents, the agonist-induced GIRK current (via
      coexpressed m2 muscarinic receptors) was inhibited by halothane. For GIRK1/GIRK4
      and GIRK1(F137S) channels this inhibition was most pronounced at low
      concentrations of the anesthetic (0.1-0.3 mM) and occurred also when channels had
      been activated by guanosine-5'-O-(3-thio)triphosphate. This inhibition, however,
      was overridden by high concentrations of halothane (0.9 mM) and augmentation of
      the agonist-induced current was observed. This increase in agonist-induced
      current was never seen with GIRK2 homo-oligomeric channels. Agonist-induced
      currents mediated by GIRK2 channels were always inhibited by halothane with an
      IC(50) value of approximately 60 microM. These data suggest a direct interaction
      of halothane with GIRK channels.

PMID- 11455016
TI  - Selective potentiation of paclitaxel (taxol)-induced cell death by mitogen
      activated protein kinase kinase inhibition in human cancer cell lines.
AB  - Activation of the mitogen-activated protein kinase (MAPK) pathway in HeLa and
      Chinese hamster ovary cells after treatment with paclitaxel (Taxol) and other
      microtubule interacting agents has been investigated. Using a trans-reporting
      system, the phosphorylation of the nuclear transcription factors Elk-1 and c-jun
      was measured. Concentration- and time-dependent activation of the Elk-1 pathway,
      mediated primarily by the extracellular signal-regulated kinase (ERK) component
      of the MAPK family, was observed. Inactive drug analogs and other cytotoxic
      compounds that do not target microtubules failed to induce similar levels of
      activation, thereby indicating that an interaction between these drugs and the
      microtubule is essential for the activation of MAPKs. Evaluation of the
      endogenous levels of MAPK expression revealed cell-dependent expression of the
      ERK, c-jun N-terminal kinase, and p38 pathways. In the case of HeLa cells, time
      dependent activation of ERK coincided with increased poly(ADP-ribose) polymerase
      (PARP) cleavage, phosphatidylserine externalization, and increased accumulation
      of cells in G2/M. In both cell lines, inhibition of ERK activity potentiated
      paclitaxel-induced PARP cleavage and phosphatidylserine externalization,
      suggesting that ERK activity coincided with, but did not mediate, the cytotoxic
      effects of paclitaxel. We evaluated the nature of the interaction between
      paclitaxel and the MAPK kinase inhibitor U0126 in three cell lines, on the basis
      of a potential chemotherapeutic advantage of paclitaxel plus ERK inhibition. Our
      data confirmed additivity in those cells lines that undergo paclitaxel-induced
      ERK activation, and antagonism in cells with low ERK activity, suggesting that in
      tumors with high ERK activity, there may be an application for this strategy in
      therapy.

PMID- 11455017
TI  - Overexpression of glutathione S-transferase II and multidrug resistance transport
      proteins is associated with acquired tolerance to inorganic arsenic.
AB  - Recent work shows that long-term exposure to low levels of arsenite induces
      malignant transformation in a rat liver epithelial cell line. Importantly, these
      chronic arsenic-exposed (CAsE) cells also develop self-tolerance to acute arsenic
      exposure. Tolerance is accompanied by reduced cellular arsenic accumulation,
      suggesting a mechanistic basis for reduced arsenic sensitivity. The present study
      examined the role of xenobiotic export pumps in acquired arsenic tolerance.
      Microarray analysis of CAsE cells showed increased expression of the genes
      encoding for glutathione S-transferase Pi (GST-Pi), multidrug resistance
      associated protein genes (MRP1/MRP2, which encode for the efflux transporter
      Mrp1/Mrp2) and the multidrug resistance gene (MDR1, which encodes for the efflux
      transporter P-glycoprotein). These findings were confirmed at the transcription
      level by reverse transcription-polymerase chain reaction and at the translation
      level by Western-blot analysis. Acquired arsenic tolerance was abolished when
      cells were exposed to ethacrynic acid (an inhibitor of GST-Pi), buthionine
      sulfoximine (a glutathione synthesis inhibitor), MK571 (a specific inhibitor for
      Mrps), and PSC833 (a specific inhibitor for P-glycoprotein) in dose-dependent
      fashions. MK571, PSC833, and buthionine sulfoximine markedly increased cellular
      arsenic accumulation. Consistent with a role for multidrug resistance efflux
      pumps in arsenic resistance, CAsE cells were found to be cross-resistant to
      cytotoxicity of several anticancer drugs, such as vinblastine, doxorubicin,
      actinomycin-D, and cisplatin, that are also substrates for Mrps and P
      glycoprotein. Thus, acquired tolerance to arsenic is associated with increased
      expression GST-Pi, Mrp1/Mrp2 and P-glycoprotein, which function together to
      reduce cellular arsenic accumulation.

PMID- 11455018
TI  - Overexpression of cytochrome P450 CYP2J2 protects against hypoxia-reoxygenation
      injury in cultured bovine aortic endothelial cells.
AB  - CYP2J2 is abundant in human heart and its arachidonic acid metabolites, the
      epoxyeicosatrienoic acids (EETs), have potent vasodilatory, antiinflammatory and
      cardioprotective properties. This study was designed to examine the role of
      CYP2J2 in hypoxia-reoxygenation-induced injury in cultured bovine aortic
      endothelial cells (BAECs). Early passage BAECs were exposed to 24-h hypoxia
      followed by 4-h reoxygenation (HR). HR resulted in cell injury, as indicated by
      significant increases in lactate dehydrogenase (LDH) release and trypan blue
      stained cells (p < 0.01) and was associated with a decrease in CYP2J2 protein
      expression. Transfection of BAECs with the CYP2J2 cDNA resulted in increased
      CYP2J2 expression and arachidonic acid epoxygenase activity, compared with cells
      transfected with an irrelevant green fluorescent protein (GFP) cDNA. HR induced
      significant injury in GFP-transfected BAECs, as indicated by increases in LDH
      release and trypan blue-stained cells (p < 0.01); however, the HR-induced injury
      was markedly attenuated in CYP2J2-transfected cells (p < 0.01). HR increased
      cellular 8-iso-prostaglandin F(2alpha) (p < 0.05), and decreased eNOS expression,
      L-arginine uptake and conversion, and nitrite production (p < 0.01) in GFP
      transfected BAECs. CYP2J2 transfection attenuated the HR-induced increase in 8
      iso-prostaglandin F(2alpha) (p < 0.05) and decreased the amount of extracellular
      superoxide detected by cytochrome c reduction under normoxic conditions (p <
      0.05) but did not significantly affect HR-induced decreases in eNOS expression, L
      arginine uptake and conversion, and nitrite production. Treatment of BAECs with
      synthetic EETs and/or epoxide hydrolase inhibitors also showed protective effects
      against HR injury (p < 0.05). These observations suggest: (1) HR results in
      endothelial injury and decreased CYP2J2 expression; (2) transfection with the
      CYP2J2 cDNA protects against HR injury; and (3) the cytoprotective effects of
      CYP2J2 may be mediated, at least in part, by antioxidant effects.

PMID- 11455019
TI  - G protein-coupled receptor kinases 3 and 6 use different pathways to desensitize
      the endogenous M3 muscarinic acetylcholine receptor in human SH-SY5Y cells.
AB  - We have investigated the effects of G protein-coupled receptor kinase (GRK) 3 and
      GRK6 on the phosphorylation and regulation of the M3 muscarinic acetylcholine
      receptor (mACh) endogenously expressed in SH-SY5Y cells. Overexpression of GRK3
      or GRK6 enhanced M3 mACh receptor phosphorylation after high-concentration
      methacholine (100 microM, 1 min) addition. However, GRK6 was more potent,
      increasing receptor phosphorylation even after low (3 microM, 1 min) agonist
      stimulation. Compared with plasmid-transfected control cells expressing
      equivalent M3 mACh receptor number, GRK3- or GRK6-overexpressing cells exhibited
      a reduced phospholipase C activity reflected by a lower accumulation of total
      [3H]inositol phosphates and Ins(1,4,5)P3 mass. In addition, direct stimulation of
      G protein activation of phospholipase C (by AlF4(-)) was inhibited in GRK3- but
      not GRK6-overexpressing cells. Guanosine-5'-O-(3-[35S]thio)triphosphate binding
      and immunoprecipitation of Galpha(q/11) indicated that acute methacholine
      stimulated receptor/Galpha(q/11) coupling was unaffected by GRK overexpression.
      In contrast, agonist pretreatment of cells for 3 min caused M3 mACh receptor
      uncoupling from Galpha(q/11), which was markedly enhanced by GRK6 overexpression,
      particularly at lower agonist pretreatment concentrations. However, the increased
      M3 mACh receptor phosphorylation seen in clones overexpressing GRK3 was not
      accompanied by increased receptor-Galpha(q/11) uncoupling. Overall, these data
      suggest that GRK3 and GRK6 use different pathways to desensitize the M3 mACh
      receptor. GRK6 seems to act as a classical GRK, inducing increased receptor
      phosphorylation accompanied by an uncoupling of receptor and Galpha(q/11).
      Conversely, GRK3 may cause desensitization independently of receptor
      phosphorylation, possibly via Gbetagamma binding and/or direct Galpha(q) binding
      via its regulator of G protein signaling domain to inhibit phospholipase C
      activity.

PMID- 11455020
TI  - delta-Opioid receptor gene: effect of Sp1 factor on transcriptional regulation in
      vivo.
AB  - delta-Opioid receptor (DOR) promoter exhibited a cell-type-specific expression
      pattern. Protein-DNA interactions in this promoter were identified by dimethyl
      sulfate in vivo footprinting analysis of NG108-15 cells, expressing endogenous
      DOR. Complete protection of the putative Sp1 cis-element and partial protection
      of the sequence defined as X-NotI in the basal promoter were observed only in the
      G0/G1 phase of the cell cycle. No protection was detected in Neuro2A cells that
      do not express DOR. In vivo formaldehyde cross-linking confirmed Sp1 factor
      binding to its cis-acting element during the G0/G1 phase. The functional
      significance of these Sp1 and X-NotI sites was evaluated by transient
      transfection analysis. Northern blot analysis and nuclear run-off assays revealed
      maximum DOR mRNA level and transcription rate, respectively, during the G0/G1
      phase of NG108-15 cells. In summary, the protein-DNA interactions at the Sp1 and
      X-NotI sites are necessary for cell cycle-dependent and cell-type-specific up
      regulated DOR gene expression.

PMID- 11455021
TI  - A peptide derived from bee venom-secreted phospholipase A2 inhibits replication
      of T-cell tropic HIV-1 strains via interaction with the CXCR4 chemokine receptor.
AB  - We have previously shown that secreted phospholipases A2 (sPLA2) from bee and
      snake venoms have potent anti-human immunodeficiency virus (HIV) activity. These
      sPLA2s block HIV-1 entry into host cells through a mechanism linked to sPLA2
      binding to cells. In this study, 12 synthetic peptides derived from bee venom
      sPLA2 (bvPLA2) have been tested for inhibition of HIV-1 infection. The p3bv
      peptide (amino acids 21 to 35 of bvPLA2) was found to inhibit the replication of
      T-lymphotropic (T-tropic) HIV-1 isolates (ID(50) = 2 microM) but was without
      effect on monocytotropic (M-tropic) HIV-1 isolates. p3bv was also found capable
      of preventing the cell-cell fusion process mediated by T-tropic HIV-1 envelope.
      Finally, p3bv can inhibit the binding of radiolabeled stromal cell-derived factor
      (SDF)-1alpha, the natural ligand of CXCR4, and the binding of 12G5, an anti-CXCR4
      monoclonal antibody. Taken together, these results indicate that p3bv blocks the
      replication of T-tropic HIV-1 strains by interacting with CXCR4. Its mechanism of
      action however appears distinct from that of bvPLA2 because the latter inhibits
      replication of both T-tropic and M-tropic isolates and does not compete with SDF
      1alpha and 12G5 binding to CXCR4.

PMID- 11455022
TI  - Modulation of protein kinase A activation by fibronectin matrix proteins at
      developing neuromuscular synapses in Xenopus laevis cell cultures.
AB  - Extracellular matrix proteins, such as fibronectin, laminin, and collagen, have
      been implicated in a wide variety of cellular properties, which include cell
      adhesion, migration, differentiation, and proliferation. In this study, we
      investigated the modulation of protein kinase A (PKA) activity by matrix proteins
      at developing motoneurons. The cultures of spinal neurons and myotomal cells were
      prepared from 1-day-old Xenopus laevis embryos. Spontaneous synaptic currents
      (SSC) were recorded from innervated myocytes of natural synapses by whole-cell
      voltage-clamped recordings (V(h) = -60 to approximately -65 mV). Bath application
      of agents, which directly or indirectly activate PKA, such as forskolin (20
      microM), dibutyryl cAMP (DBcAMP) (1 mM), isoproterenol (10 microM), or albuterol
      (10 microM), significantly increased SSC frequency in cultures grown on
      fibronectin (FN)-coated substratum, but not on laminin- or collagen-coated
      glasses. The evoked synaptic currents increased in response to forskolin in
      neurons grown on FN substratum. Triflavin, an Arg-Gly-Asp-dependent disintegrin,
      inhibited potentiating action of isoproterenol in neurons grown on FN substratum,
      suggesting that integrin is involved in the potentiation of the PKA pathway in
      the regulation of acetylcholine (ACh) release. There is collaboration of
      neurotrophic factors and the FN matrix in regulating synaptic transmission in
      response to DBcAMP. Chronic treatment with neurotrophic factors, such as ciliary
      neurotrophic factor (150 ng/ml), glial cell line-derived neurotrophic factor (30
      ng/ml), or neurotrophin-3 (50 ng/ml), enhanced the SSC-increasing action of
      DBcAMP in neurons grown on FN-coated glasses. These results suggest that the FN
      matrix potentiates synaptic transmission in response to PKA activation.
      Neurotrophic factors may collaborate with FN to regulate spontaneous ACh
      secretion at developing motoneurons, which may play an important role in the
      maturation of embryonic neuromuscular synapses.

PMID- 11455023
TI  - Structural constraints affect the metabolism of 7-ethyl-10-[4-(1-piperidino)-1
      piperidino]carbonyloxycamptothecin (CPT-11) by carboxylesterases.
AB  - 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin [CPT-11
      (irinotecan)] is a water-soluble camptothecin-derived prodrug that is activated
      by esterases to yield the potent topoisomerase I poison SN-38. We identified a
      rabbit liver carboxylesterase (CE) that was very efficient at CPT-11 metabolism;
      however, a human homolog that was more than 81% identical to this protein
      activated the drug poorly. Recently, two other human CEs have been isolated that
      are efficient in the conversion of CPT-11 to SN-38, yet both demonstrate little
      homology to the rabbit protein. To understand this phenomenon, we have
      characterized a series of esterases from human and rabbit, including several
      chimeric proteins, for their ability to metabolize CPT-11. Computer predictive
      modeling indicated that the ability of each enzyme to activate CPT-11 was
      dependent on the size of the entrance to the active site. Kinetic studies with a
      series of nitrophenyl and naphthyl esters confirmed these predictions, indicating
      that activation of CPT-11 by a CE is constrained by size-limited access of the
      drug to the active site catalytic amino acid residues.

PMID- 11455024
TI  - Suppression of cellular invasion by activated G-protein subunits Galphao,
      Galphai1, Galphai2, and Galphai3 and sequestration of Gbetagamma.
AB  - It was shown previously that platelet-activating factor receptors (PAF-Rs)
      inhibit invasiveness of colonic and kidney epithelial cells induced by the src
      and Met oncogenes via a pertussis toxin-sensitive mechanism. Therefore, Madin
      Darby canine kidney (MDCKts.src) cells were stably transfected with
      constitutively activated forms of Galphao, Galphai1, Galphai2, Galphai3
      (AGalphao/i), two Gbetagamma sequestering proteins [C-terminal end of beta
      adrenergic receptor kinase (ct-betaARK) and the Galphat subunit of retinal G
      protein transducin], and Gbeta1-Ggamma2 subunits alone or in combination.
      Cellular invasion induced by src, Met, and leptin was abrogated by the
      AGalphao/i, ct-betaARK, and Galphat-positive clones, but was induced by
      coexpression of Gbeta1gamma2. In contrast, invasion stimulated by the trefoil
      factors (TFFs) pS2 and intestinal trefoil factor in MDCKts.src cells or human
      colonic epithelial cells PCmsrc and HCT8/S11 was insensitive to PAF, AGalphao,
      AGalphai1, and AGalphai2, but was abolished by AGalphai3 and the protease
      activated receptor-1 (PAR-1) agonist thrombin receptor-activating peptide.
      Depletion of free Gbetagamma heterodimers by ct-betaARK resulted in a remarkable
      decrease of cellular adhesion and spreading on collagen matrix. Our data
      demonstrate the following: 1) PAF-Rs impair cellular invasion induced by src,
      Met, and leptin via the activation of Galphao and Galphai1 to -3; 2) invasion
      induced by TFFs is selectively inhibited by PAR-1 receptors and Galphai3
      activation; and 3) Gbetagamma dimers are required as positive effectors of
      invasion pathways induced by oncogenes and epigenetic factors. Thus,
      redistribution of Galphao/Galphai and Gbeta/gamma heterotrimeric G-proteins by
      PAF-R and PAR-1 exert differential functions on positive and negative signaling
      pathways involved in cellular invasion and may serve as potential targets for
      anticancer therapy.

PMID- 11455025
TI  - Modeling and mutational analysis of a putative sodium-binding pocket on the
      dopamine D2 receptor.
AB  - A homology model of the dopamine D2 receptor was constructed based on the crystal
      structure of rhodopsin. A putative sodium-binding pocket identified in an earlier
      model (PDB ) was revised. It is now defined by Asn-419 backbone oxygen at the
      apex of a pyramid and Asp-80, Ser-121, Asn-419, and Ser-420 at each vertex of the
      planar base. Asn-423 stabilizes this pocket through hydrogen bonds to two of
      these residues. Highly conserved Asn-52 is positioned near the sodium pocket,
      where it hydrogen-bonds with Asp-80 and the backbone carbonyl of Ser-420.
      Mutation of three of these residues, Asn-52 in helix 1, Ser-121 in helix 3, and
      Ser-420 in helix 7, profoundly altered the properties of the receptor. Mutants in
      which Asn-52 was replaced with Ala or Leu or Ser-121 was replaced with Leu
      exhibited no detectable binding of radioligands, although receptor
      immunoreactivity in the membrane was similar to that in cells expressing the wild
      type D2L receptor. A mutant in which Asn-52 was replaced with Gln, preserving
      hydrogen-bonding capability, was similar to D2L in affinity for ligands and
      ability to inhibit cAMP accumulation. Mutants in which either Ser-121 or Ser-420
      was replaced with Ala or Asn had decreased affinity for agonists (Ser-121), but
      increased affinity for the antagonists haloperidol and clozapine. Interestingly,
      the affinity of these Ser-121 and Ser-420 mutants for substituted benzamide
      antagonists showed little or no dependence on sodium, consistent with our
      hypothesis that Ser-121 and Ser-420 contribute to the formation of a sodium
      binding pocket.

PMID- 11455026
TI  - Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5)
      expressed among African Americans.
AB  - CYP2C9 is a polymorphic gene for which there are four known allelic variants;
      CYP2C9*1, CYP2C9*2, CYP2C9*3, and CYP2C9*4. In the present study, DNA from 140
      European Americans and 120 African Americans was examined by single-strand
      conformational polymorphism and restriction fragment length polymorphism
      analyses, resulting in the identification of a new CYP2C9 variant, CYP2C9*5. This
      variant is derived from a C1080G transversion in exon 7 of CYP2C9 that leads to
      an Asp360Glu substitution in the encoded protein. The CYP2C9*5 variant was found
      to be expressed only in African Americans, such that approximately 3% of this
      population carries the CYP2C9*5 allele. The variant was expressed in, and
      purified from, insect cells infected with a recombinant baculovirus. Comparative
      kinetic studies using the purified wild-type protein CYP2C9*1; the Ile359Leu
      variant, CYP2C9*3; and the Asp360Glu variant, CYP2C9*5 were carried out using (S)
      warfarin, diclofenac, and lauric acid as substrates. The major effect of the
      Asp360Glu mutation was to increase the K(m) value relative to that of CYP2C9*1
      for all three substrates: 12-fold higher for (S)-warfarin 7-hydroxylation, 5-fold
      higher for the 4'-hydroxylation of diclofenac, and 3-fold higher for the omega-1
      hydroxylation of lauric acid. V(max) values differed less than K(m) values
      between the CYP2C9*1 and CYP2C9*5 proteins. In vitro intrinsic clearances for
      CYP2C9*5, calculated as the ratio of V(max)/K(m), ranged from 8 to 18% of
      CYP2C9*1 values. The corresponding ratio for CYP2C9*3 was 4 to 13%. Accordingly,
      the in vitro data suggest that carriers of the CYP2C9*5 allele would eliminate
      CYP2C9 substrates at slower rates relative to persons expressing the wild-type
      protein.

PMID- 11455027
TI  - Loss of cyp1a1 messenger rna expression due to nonsense-mediated decay.
AB  - Clones of the mouse hepatoma cell line Hepa1c1c7 (Hepa-1) with lesions in the
      Cyp1a1 gene were isolated previously. A subset of these clones fails to express
      CYP1A1 mRNA even when treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin, which
      induces this mRNA in wild-type Hepa-1 cells. The current investigation sought an
      explanation for this phenotype in one of these clones, c33. Loss of mRNA
      expression in c33 was shown to be caused by mutational changes in the Cyp1a1 gene
      rather than by its epigenetic silencing. No mutations were identified in the 5'
      flanking region of the Cyp1a1 gene, containing the promoter and dioxin-responsive
      enhancer sequences. A single nucleotide insertion occurred at nucleotide 418 in
      the coding region of one Cyp1a1 allele, and a single nucleotide insertion
      occurred at nucleotide 465 in the other allele in c33. These sequence alterations
      were confirmed in the genomic DNA of the clone. Both insertions generate a
      premature termination codon at codon 172. This termination codon occurs in a
      position within the intron/exon structure of the Cyp1a1 gene such that the
      encoded mRNA should be subject to "nonsense-mediated decay" (NMD). Inhibition of
      protein synthesis is known to reverse NMD. The protein synthesis inhibitors
      cycloheximide and puromycin fully restored CYP1A1 mRNA expression to c33 cells,
      supporting the notion that NMD degrades CYP1A1 mRNA in this strain. The mutations
      identified in the coding region of c33 provide an explanation, therefore, for its
      loss of both CYP1A1 enzymatic activity and inducible CYP1A1 mRNA expression.

PMID- 11455028
TI  - Histone H3 phosphorylation is coupled to poly-(ADP-ribosylation) during reactive
      oxygen species-induced cell death in renal proximal tubular epithelial cells.
AB  - Although the cellular response to chemical-induced stress is relatively well
      characterized, particularly the response to DNA damage, factors that govern the
      outcome of the stress response (cell survival or cell death) are less clearly
      defined. In this context, the mitogen-activated protein kinase (MAPK) family
      responds to a variety of physical and chemical stresses. The activation of MAPKs,
      especially the extracellular-regulated protein kinase subfamily, seems to play a
      causal role in death of renal proximal tubular epithelial cells (LLC-PK1) induced
      by reactive oxygen species (ROS). In this study, we show that extracellular
      signal receptor-activated kinase (ERK) activation may be coupled with LLC-PK1
      cell death via changes in chromatin structure, which is mediated by increases in
      the phosphorylation of histone H3 (a post-translational modification required for
      both chromosome condensation and segregation during mitosis) and premature
      chromatin/chromosomal condensation, leading to cell death. In support of this
      view, 2,3,5-tris-(glutathione-S-yl)hydroquinone (TGHQ)-induced phosphorylation of
      histone H3 is accompanied by increases in chromatin condensation, as observed
      with the use of 4,6-diamidino-2-phenylindole-fluorescent staining, and by
      decreases in the sensitivity of chromatin to digestion by micrococcal nuclease.
      Changes in chromatin structure precede cell death. TGHQ-induced histone H3
      phosphorylation and chromatin condensation are inhibited by PD098059, which
      selectively inhibits MAPK kinase, an upstream regulator of ERKs. Moreover,
      histone phosphorylation is modulated by poly(ADP-)ribosylation. Thus, the
      inhibition of poly(ADP-ribose)polymerase with 3-aminobenzamide prevents histone
      H3 phosphorylation and increases cell survival, suggesting that ADP-ribosylation
      and histone H3 phosphorylation are coupled in this model of ROS-induced DNA
      damage and cell death. The coupling of histone phosphorylation with ribosylation
      has not been previously demonstrated.

PMID- 11455029
TI  - Diagnosis of bladder cancer with urinary cytology, immunocytology and DNA-image
      cytometry.
AB  - DNA-image-cytometry and antibodies directed against the Lewis X- and the 486p
      3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for
      the detection of bladder cancer. Cytology, immunocytology and DNA-image-cytometry
      were performed in spontaneously voided urine samples and barbotage bladder
      washings from 71 patients. The DNA content was determined using the CM-1
      Cytometer according to the recommendation of the ESCAP Consensus Report on
      Standardization of DNA-image-cytometry (1995). For immunocytological examination
      we used the monoclonal anti Lewis X antibody P-12 and antibody 486p 3/12. All
      patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or
      transurethral resection was done. Histological findings revealed 31 patients with
      transitional cell carcinomas of different stages and grades of malignancy. 40
      patients had various benign diseases of the urinary bladder. Cytology yielded a
      sensitivity of 68% and a specificity of 100%. DNA aneuploidy was detected in 81%
      of cancer patients with a specificity of 100%. By combination of these two
      methods the overall sensitivity increased to 87%. Immunocytology with Lewis X and
      486p 3/12 antibodies showed reactivity in 84% and 87% in combination with a
      specificity of 80% and 70%, respectively. By combining urinary cytology,
      immunocytology and/or DNA-image-cytometry the overall sensitivity increased to
      94% with no change in specificity. DNA-image-cytometry should be used to evaluate
      particularly urothelial cells suspicious for malignancy in urinary specimens.
      Because of low specificity the monoclonal antibodies against Lewis X- and 486p
      3/12 antigens are not helpful in screening for bladder cancer. Nevertheless,
      their high sensitivity may justify their use in case DNA image cytometry is not
      available and in the follow up of patients with transitional cell carcinoma.

PMID- 11455030
TI  - Towards a genetic-based classification of human lung cancer.
AB  - Lung cancer is a highly aggressive neoplasm which is reflected by a multitude of
      genetic aberrations being detectable on the chromosomal and molecular level. In
      order to understand this seemingly genetic chaos, we performed Comparative
      Genomic Hybridisation (CGH) in a large collective of human lung carcinomas
      investigating different tumor entities as well as multiple individual tumour
      specimens of single patients. Despite the considerable genetic instability being
      reflected by the well known morphological heterogeneity of lung cancer the
      comparison of different tumour groups using custom made computer software
      revealed recurrent aberration patterns and highlighted chromosomal imbalances
      that were significantly associated with morphological histotypes and biological
      phenotypes. Specifically we identified imbalances in NSCLC being associated with
      metastasis formation which are typically present in SCLC thus explaining why the
      latter is such an aggressive neoplasm characterized by widespread tumor
      dissemination. Based on the genetic data a new model for the development of SCLC
      is presented. It suggests that SCLC evolving from the same stem cell as NSCLC
      should be differentiated into primary and secondary tumors. Primary SCLC
      corresponding to the classical type evolved directly from an epithelial precursor
      cell. In contrast, secondary SCLC correlating with the combined SCLC develops via
      an NSCLC intermediate. In addition, we established libraries of differentially
      expressed genes from different human lung cancer types to identify new candidate
      genes for several of the chromosomal subregions identified by CGH. In this
      review, we summarise the status of our results aiming at a refined classification
      of lung cancer based on the pattern of genetic aberrations.

PMID- 11455031
TI  - Genetic instability promotes the acquisition of chromosomal imbalances in T1b and
      T1c breast adenocarcinomas.
AB  - In order to evaluate biological and genetic properties of early breast carcinomas
      we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and
      T1c with respect to the nuclear DNA content, the expression pattern of Ki-67,
      cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results
      show that T1b carcinomas (6-10 mm, n=17) were frequently near-diploid (53%) with
      low proliferative activity and staining patterns of p53 and p21WAF1 that suggest
      the presence of wild type protein. The majority (12/16) of the T1c tumors (11-20
      mm), however, was aneuploid, and proliferative activity and p53 expression were
      increased. Larger tumor size correlated with an increasing number of chromosomal
      copy number changes and in particular with regional amplifications. High level
      copy number increases (amplifications), however, were found exclusively in the
      aneuploid tumors. Amplification events correlated with elevated cyclin A and
      reduced p27 expression, respectively. Our results suggest that the sequential
      acquisition of genomic imbalances during tumor progression is accelerated in
      aneuploid tumors, and may contribute to the increased malignancy potential.

PMID- 11455032
TI  - Spectral imaging of multi-color chromogenic dyes in pathological specimens.
AB  - We have investigated the use of spectral imaging for multi-color analysis of
      permanent cytochemical dyes and enzyme precipitates on cytopathological
      specimens. Spectral imaging is based on Fourier-transform spectroscopy and
      digital imaging. A pixel-by-pixel spectrum-based color classification is
      presented of single-, double-, and triple-color in situ hybridization for
      centromeric probes in T24 bladder cancer cells, and immunocytochemical staining
      of nuclear antigens Ki-67 and TP53 in paraffin-embedded cervical brush material
      (AgarCyto). The results demonstrate that spectral imaging unambiguously
      identifies three chromogenic dyes in a single bright-field microscopic specimen.
      Serial microscopic fields from the same specimen can be analyzed using a spectral
      reference library. We conclude that spectral imaging of multi-color chromogenic
      dyes is a reliable and robust method for pixel color recognition and
      classification. Our data further indicate that the use of spectral imaging (a)
      may increase the number of parameters studied simultaneously in pathological
      diagnosis, (b) may provide quantitative data (such as positive labeling indices)
      more accurately, and (c) may solve segmentation problems currently faced in
      automated screening of cell- and tissue specimens.

PMID- 11455033
TI  - Rapid stereology based quantitative immunohistochemistry of dendritic cells in
      lymph nodes: a methodological study.
AB  - This study was done to arrive at a fast and reliable protocol for assessment of
      fractional volumes of immunohistochemically stained dendritic cells in lymph
      nodes. Twenty axillary lymph nodes of patients with locally advanced breast
      cancer were immuno-histochemically stained with an S100 antibody. Fractional
      volumes of dendritic cells were assessed by stereology based quantitative
      immunohistochemistry using an interactive video overlay system including an
      automated microscope. The gold standard percentage of dendritic cells was the
      fractional volume of S100 stained cells in 500 fields systematically spread over
      the whole lymph node. Then, in a computer simulation, different sample sizes (1
      200 fields of vision) were tested and the coefficient of variation (CV) for each
      sample size was calculated. The CV dropped with increasing sample size. A sample
      size of 100 fields of vision appeared to be optimal. Intra- and interobserver
      reproducibility appeared to be good (correlation coefficients of 0.95 and 0.86,
      respectively) when re-analyzing the cases with the established protocol. In
      conclusion, a fast and reliable assessment of the fractional volume of dendritic
      cells in lymph nodes is possible with semi-automated quantitative immuno
      histochemistry. This method will form the base for further clinical studies into
      the immunological response in lymph nodes of patients with locally advanced
      breast cancer.

PMID- 11455034
TI  - In situ reverse transcriptase-nested polymerase chain reaction to identify
      intracellular nucleic acids without the necessity of DNAse pretreatment and
      hybridisation.
AB  - In the present study a protocol of in situ reverse transcriptase-nested
      polymerase chain reaction (in situ RT-nested PCR) was examined based on the
      following modifications. (i) To exclude false positive signals caused by "DNA
      repair mechanisms" and "endogenous priming", a two-step PCR was applied after
      reverse transcription. The first step was performed in the presence of extrinsic
      primers and unlabeled nucleotides with a maximum of PCR cycles possible without
      destroying the cell morphology. The second step consisted of only one
      annealing/elongation reaction, the target sequence marked by addition of
      digoxigenin-labeled nucleotides and intrinsic primers. (ii) In order to prevent
      amplifications of genomic DNA nested primer pairs were applied crossing intron
      sequences. (iii) To minimize the diffusion of PCR products in cells, the
      extrinsic primers were extended with complementary 5(prime, variant)-tails. This
      approach results in the generation of high molecular weight concatamers during
      PCR cycles. By applying this protocol, immunostainings specific for phospholipase
      A2 of type IIA mRNA were exclusively detectable in the cytoplasm of HepG2
      hepatoma cells, which were used as a model system, whereas the nuclei were
      unstained. Multiple control experiments yielded completely negative results.
      These data suggest that the in situ RT-nested PCR, which in comparison to the
      method of in situ RT-PCR-in situ-hybridisation is simpler and less time
      consuming, can be used as an alternative approach to identify intracellular
      nucleic acids.

PMID- 11455035
TI  - Amplification at 9p in cervical carcinoma by comparative genomic hybridization.
AB  - DNA copy number changes were studied by comparative genomic hybridization on 10
      tumor specimens of squamous cell carcinoma of cervix obtained from Korean
      patients. DNA was extracted from paraffin-embedded sections after removal of non
      malignant cells by microdissection technique. Copy number changes were found in
      8/10 tumors. The most frequent changes were chromosome 19 gains (n=6) and losses
      on chromosomes 4 (n=4), 5 (n=3), and 3p (n=3). A novel finding was amplification
      in chromosome arm 9p21-pter in 2 cases. Gains in 1, 3q, 5p, 6p, 8q, 16p, 17, and
      20q and losses at 2q, 6q, 8p, 9q, 10p, 11, 13, 16q, and 18q were observed in at
      least one of the cases.

PMID- 11455036
TI  - Flow cytometric DNA analysis using cytokeratin labeling for identification of
      tumor cells in carcinomas of the breast and the female genital tract.
AB  - Flow cytometric assessment of DNA-ploidy and S-phase fraction in malignant tumors
      is compromised by the heterogeneity of cell subpopulations derived from the
      malignant and surrounding connective tissue, e.g., tumor, stromal and
      inflammatory cells. To evaluate the effect on quality of DNA cell cycle analysis
      and determination of DNA ploidy, cytokeratin labeling of epithelial cells was
      used for tumor cell enrichment in breast, ovarian, cervical and endometrial
      cancer prior to DNA analysis. In a prospective study, tumor cell subpopulations
      of 620 malignant tumors were labeled by a FITC-conjugated cytokeratin antibody
      (CK 5, 6, CK18 and CK 5, 6, 8 and CK 17, respectively) prior to flow cytometric
      cell cycle analysis. Compared to total cell analysis, detection rate of DNA
      aneuploid tumors following cytokeratin labeling was increased from 62% to 76.5%
      in breast cancer, from 68% to 77% in ovarian cancer, from 60% to 80% in cervical
      cancer and from 30% to 53% in endometrial cancer. Predominantly in DNA-diploid
      tumors, a significantly improved detection of S-phase fraction of the tumor cells
      was shown due to the elimination of contaminating nonproliferating "normal
      cells". S-phase fraction following tumor cell enrichment was increased by 10%
      (mean) following cytokeratin staining in ovarian and endometrial cancer, by 30%
      in breast cancer and even by 70% in cervical cancer compared to total cell
      analysis. Thus, diagnostic accuracy of DNA-analysis was enhanced by cytokeratin
      labeling of tumor cells for all tumor entities investigated.

PMID- 11455037
TI  - Applications of SPECT in cognitive neuroscience, neurology and psychiatry.

PMID- 11455038
TI  - Probing cortical sites of antipsychotic drug action with in vivo receptor
      imaging.
AB  - Imaging receptors using radioactive ligands has allowed direct determination of
      the sites of action of antipsychotic drugs. Initial studies relating
      antipsychotic drug efficacy to action at striatal dopamine D2-like receptors have
      recently been undermined. Developments in imaging extrastriatal dopamine D2-like
      receptors suggest rather that antagonism of these receptors in the temporal
      cortex is the common site of action for antipsychotic drugs, with occupancy at
      striatal receptors relating more closely to extrapyramidal side effects. Further
      work into dopamine receptor subtypes and other receptor groups such as serotonin
      and GABA neurotransmitters awaits the development of suitable probes, but there
      are some initial finding. Again a main site of antipsychotic drug action is at
      cortical levels with high degrees of cortical D1 and 5HT2a receptor occupancy
      attained particularly by atypical antipsychotic drugs.

PMID- 11455039
TI  - Single photon emission tomography imaging in parkinsonian disorders: a review.
AB  - Parkinsonian symptoms are associated with a number of neurodegenerative
      disorders, such as Parkinson's disease, multiple system atrophy and progressive
      supranuclear palsy. Pathological evidence has shown clearly that these disorders
      are associated with a loss of neurons, particularly in the nigrostriatal
      dopaminergic pathway. Positron emission tomography (PET) and single photon
      emission tomography (SPECT) now are able to visualise and quantify changes in
      cerebral blood flow, glucose metabolism, and dopaminergic function produced by
      parkinsonian disorders. Both PET and SPECT have become important tools in the
      differential diagnosis of these diseases, and may have sufficient sensitivity to
      detect neuronal changes before the onset of clinical symptoms. Imaging is now
      being utilised to elucidate the genetic contribution to Parkinson's disease, and
      in longitudinal studies to assess the efficacy and mode of action of
      neuroprotective drug and surgical treatments. This review summarises recent
      applications of SPECT imaging in the study of parkinsonian disorders, with
      particular reference to the increasing role it is playing in the understanding,
      diagnosis and management of these diseases.

PMID- 11455040
TI  - Analysis of HMPAO SPECT scans in head injury using Statistical Parametric
      Mapping.
AB  - The paper examines the ability of Statistical Parametric Mapping (SPM) to
      contribute towards the quantitative analysis of HMPAO SPECT images containing
      lesions. A validation study is described in which SPECT images were created that
      contained synthetic lesions and were analysed with SPM. The study established a
      set of guidelines concerning the alignment, smoothing, and statistical analysis
      of images. These were then applied to analysis of SPECT scans from head injured
      patients. A demonstration is given of the use of SPM to identify localised blood
      flow abnormalities associated with cognitive deficits after head injury.
      Correlations between blood flow abnormalities and a test of visual memory are
      illustrated.

PMID- 11455041
TI  - Subcortical hypoperfusion following surgery for aneurysmal subarachnoid
      haemorrhage: implications for cognitive performance?
AB  - The incidence and severity of cognitive deficits after surgery for aneurysmal
      subarachnoid haemorrhage and their relationship to aneurysm site remains
      controversial. The aim of this study was to investigate the pattern of regional
      cerebral blood flow which exists in patients one year post-surgery and to
      identify whether different patterns exist which may be related to the type of
      cognitive deficit or the location of the aneurysm. 62 patients underwent
      cognitive assessment and HMPAO SPECT imaging at a mean time of 12 months
      following surgery. Results were compared to those from healthy control subjects
      (n = 55 for neuropsychological testing; n = 14 for SPECT imaging). In the patient
      group, significant stable cognitive deficits occurred in all cognitive domains
      but no cognitive measure differentiated aneurysm site. On SPECT images,
      statistical parametric mapping identified a large common area of subcortical
      hypoperfusion in the patient group as a whole. The findings of this study suggest
      a possible link between reduced subcortical function and the extent and severity
      of cognitive deficits.

PMID- 11455042
TI  - The neuroactivation of cognitive processes investigated with SPECT.
AB  - The last ten years have seen the development and expansion of an exciting new
      field of neuroscientific research; functional mapping of the human brain. Whilst
      many of the questions addressed by this area of research could be answered using
      SPECT, relatively few SPECT activation studies of this kind have been carried
      out. The present paper combines an evaluation of SPECT procedures used for
      neuroactivation studies, and their comparison with other imaging modalities
      (i.e., PET and fMRI), with a review of SPECT neuroactivation studies that yield
      information concerning normal brain function with a particular emphasis on the
      brain activations produced by memory processing. The paper aims to describe and
      counter common misunderstandings regarding potential limitations of the SPECT
      technique, to explain and illustrate which SPECT procedures best fulfill the
      requirements of a neuroactivation study, and how best to obtain information about
      normal brain function (whether using normal healthy subjects or patients) and
      finally to highlight SPECT's potential future role in the functional mapping of
      the human brain.

PMID- 11455043
TI  - SPECT in focal epilepsies.
AB  - Brain perfusion changes during seizures were first observed in the 1930s. Single
      Photon Emission Computed Tomography (SPECT) was developed in the 1970s, and
      tracers suitable for the imaging of regional cerebral perfusion (rCP) became
      available in the 1980s. The method was first used to study rCP in the interictal
      phase, and this showed areas of low perfusion in a proportion of cases, mainly in
      patients with temporal lobe epilepsies. However, the trapping paradigm of tracers
      such as hexamethyl propyleneamine oxime (HMPAO) provided a practicable method of
      studying changes in rCP during seizures, and a literature was established in the
      late 1980s and early 1990s showing a typical sequence of changes during and after
      seizures of mesial temporal lobe origin; the ictal phase was associated with
      large increases in perfusion throughout the temporal lobe, with first the
      lateral, then the mesial temporal lobe becoming hypoperfused in the postictal
      phase. Activation and inhibition of other structures, such as the basal ganglia
      and frontal cortex, were also seen. Studies of seizures originating elsewhere in
      the brain have shown a variety of patterns of change, according to the structures
      involved. These changes have been used practically to aid the process of
      localisation of the epileptogenic zone so that epilepsy surgery can be planned.
      Some neuroreceptors (e.g. benzodiazepine receptors) can be studied using SPECT,
      and have shown localised abnormalities. SPECT has also been used to study brain
      function during the intracarotid amytal test. SPECT images of all kinds can be
      analysed using numerical techniques such as statistical parametric mapping, and
      such techniques promise to improve the yield of information from ictal studies.

PMID- 11455044
TI  - The use of statistical parametric mapping (SPM96) as a decision aid in the
      differential diagnosis of dementia using 99mTc-HMPAO SPECT.
AB  - In this study standard patterns of cerebral perfusion based on classifications
      described in the literature have been chosen and the ability of experienced
      imaging specialists to categorise the 99m Tc HMPAO SPECT scans of patients
      referred to the department for investigation of dementia has been compared before
      and after the calculation of Statistical Parametric Maps (SPM - Wellcome Dept of
      Cognitive Neurology). The primary aim was to investigate whether SPM is an
      effective decision aid and whether it impacts on the confidence of image
      reporting. The secondary aim was to examine the influence of SPM on the agreement
      between image reporting and clinical diagnosis. The results showed that there was
      a slight decrease in agreement between the imaging specialists after the
      introduction of additional information from SPM (K=0.57 to K=0.5) and that
      agreement between imaging reporting (including information from SPM) and clinical
      diagnosis was moderate (K=0.28). This study was able to confirm that SPM is
      capable of producing meaningful significance maps of individual patients in a
      routine clinical environment. However, there was no overwhelming evidence that
      SPM was able to resolve many of the dilemmas associated with the use of SPECT for
      the differential diagnosis of dementia. In particular, interpretation of SPECT
      perfusion patterns in dementia is a bigger problem than the initial
      identification of abnormalities.

PMID- 11455045
TI  - Mood and cerebral perfusion revisited.
AB  - Twenty patients with major depression and observed diurnal variations of mood
      were examined using clinical and neuropsychological measures and perfusion HMPAO
      SPECT at 8 a.m. and 8 p.m. In thirteen patients depression scores varied more
      than 15% although 4 patients with reverse diurnal variation caused mean group
      depression scores to be not different between morning and evening. There was an
      overall trend for higher depression scores to be associated with higher perfusion
      in posterior cingulate. This was mainly accounted for by significant positive
      correlations in the morning scan in posterior, but also anterior cingulate and
      medial prefrontal cortex compared with evening scans. This means that morning
      regression slopes were steeper than evening slopes. This result is discussed with
      regard to possible interpretations, such as adaptive or habituating changes
      during the day that may occur in depressed patients.

PMID- 11455046
TI  - Cingulate abnormalities associated with PANSS negative scores in first episode
      schizophrenia.
AB  - There is evidence for the involvement of the cingulate gyrus in schizophrenia. We
      present details of a Statistical Parametric Mapping (SPM) analysis of SPECT data
      from the largest study (N = 39) of drug naive schizophrenic patients. The main
      findings are that there is decreased perfusion in the anterior cingulate during
      verbal fluency when patients are compared to controls (matched individually by
      age, gender and father's social class as determined by occupation) and also that
      PANSS negative scores correlate negatively with regional cerebral blood flow in
      the cingulate gyrus (Pearson's Correlation coefficient of r = - 0.49 and
      significance p< 0.005). This suggests that measurement of change of perfusion in
      this region could be a useful biological marker in assessing the effect of
      neuroleptics on negative symptoms.

PMID- 11455047
TI  - Fatigue in patients with Parkinson's disease.
AB  - Purpose: Fatigue is a complaint frequently encountered among patients with
      Parkinson's disease (PD), however, the pathophysiological mechanism remains
      unclear. Methods: We evaluated fatigue in 26 patients clinically diagnosed to
      have PD (16 men, 10 women) and age- and sex- matched 26 controls (16 men, 10
      women) without neurological deficits by using a fatigue scale. In addition to
      neurological and neuropsychological examinations, all patients underwent MRI and
      SPECT using 99mTc-HMPAO. Results: Patients with PD had normal cognitive function
      as judged by the MMSE, but showed significantly high scores with the fatigue and
      depression scales in comparison to controls (p<0.05). There was no significant
      correlation between the depression scale and the fatigue scale, or between the
      degree of disability and the fatigue scale in patients with PD, although a
      significant correlation existed between the depression scale and the fatigue
      scale in controls. With SPECT, a significant correlation was found between the
      fatigue scale and the reduction of perfusion in the frontal lobe (p<0.05) in
      patients with PD. Conclusions: The present study suggested that sense of fatigue
      in patients with PD might be associated with frontal lobe dysfunction.

PMID- 11455048
TI  - The effect of semantic categorisation on recall memory in amnesia.
AB  - Amnesic patients were compared to a healthy control group on recall of word lists
      containing semantically-related or unrelated words. As expected on the basis of
      previous literature, the amnesic group performed below the control group on all
      measures of recall. When total recall scores for each list were used as the index
      of performance, their scores were not significantly affected by the type of list,
      unlike those of the control group. Comparison of serial position effects for
      different parts of the lists revealed that the control group derived greater
      benefit from semantic relatedness in recall of items from the middle positions.
      This effect was not shown by the amnesic group, who showed similar U-shaped
      serial position curves for recall of all three lists, and appeared to use a more
      passive recall strategy than the control group. The findings are discussed in
      relation to our current understanding of amnesic deficits.

PMID- 11455049
TI  - The processing of global and local visual information in Alzheimer's disease.
AB  - We examined the quantitative and qualitative difference of the pattern with visuo
      cognitive processing impairment in patients with early onset AD (EOAD) and late
      onset AD (LOAD). We use a visual attention task introduced by Navon (1977) to
      examine the function to integrate local visual stimuli into global image.
      Although the ability to identify solid digits ether of large and small size
      presented at the same exposure duration, EOAD performance was poor in the global
      perception especially at the short duration (20~msec). We provide evidence that
      this dysfunction is attribute to the AD pathology specific to early onset type.

PMID- 11455050
TI  - Neural measures of conscious and unconscious memory.
AB  - Neuropsychological studies of memory disorders have played a prominent role in
      the development of theories of memory. To test and refine such theories in
      future, it will be advantageous to include research that utilizes physiological
      measures of the neural events responsible for memory. Measures of the electrical
      activity of the brain in the form of event-related potentials (ERPs) provide one
      source of such information. Recent results suggest that these real-time measures
      reflect relevant encoding and retrieval operations. In particular, distinct
      electrical responses have been associated with recollective processing of words
      and with priming of visual word-form. This source of evidence can thus enrich our
      understanding of both the cognitive structure and neural substrates of human
      memory.

PMID- 11455051
TI  - Topographic mapping of P300 and frontal cognitive function in Parkinson's
      disease.
AB  - The purpose of this study was to evaluate the relationship between P300 that is
      one of the event-related potentials and frontal cognitive functions in
      Parkinson's disease (PD) without clinically apparent dementia. Subjects were 20
      PD cases 48 to 79 years of age, all of whom were within normal limits on the Mini
      Mental State examination, and 55 age-matched healthy adults. P300 was elicited
      with an auditory oddball paradigm and recorded at 15 sites on the scalp.
      Cognitive functioning of the frontal lobe was evaluated using the New Modified
      Wisconsin Card Sorting Test (WCST) and the Letter Pick-Out Test (LPOT) which
      reflects selective attention and semantic categorization. P300 latency was
      delayed in 30.0% of P300 demonstrated abnormal distribution in 20.0%. the WCST
      and the LPOT were abnormal in 15.0%, P300 latency significantly correlated with
      number of subcategories achieved on the WCST. P300 amplitude correlated with
      scores on the LPOT. These results suggest that cognitive dysfunction which linked
      partly to the frontal lobe might begin in PD even without clinically apparent
      dementia.

PMID- 11455052
TI  - Is the finding of obsessional behaviour relevant to the differental diagnosis of
      Vascular Dementia of the Binswanger Type?
AB  - Whilst carrying out a pilot study with a structured questionnaire examining the
      difference in insight between a group of patients with Alzheimer's Disease and a
      second group with Vascular Dementia of the Binswanger Type, the incidental
      observation was made that the group of patients with Vascular Dementia of the
      Binswanger Type demonstrated more obsessional behaviour than the group of
      patients with Alzheimer's Disease. The obsessional behaviour differed from
      classical obsessive compulsive disorder insofar as the subjects were unaware of
      it whilst at the same time resisting change.

PMID- 11455053
TI  - Venous leg ulcers and microcirculation.
AB  - Incompetence of venous valves do not lead per se to trophic skin changes of the
      lower limb. In severely concerned patients suffering from dermatoliposclerosis or
      venous leg ulcers retrograde pressure waves were detected in the nutritive
      capillaries of the skin by the "servo nulling" pressure measurement during
      simulated calf muscle contraction. Between the degree of trophic skin change and
      the capillary density and cutaneous oxygen partial pressure a close correlation
      was found. Healing of venous ulcers occurred only if the cutaneous
      microangiopathy in the ulcer area improved. Capillary density and transcutaneous
      oxygen partial pressure were of prognostic impact as to healing of venous ulcers.

PMID- 11455054
TI  - The relationship between reference value of old people's erythrocyte
      sedimentation rate and altitude.
AB  - In order to provide a scientific basic for a unified standard of the reference
      value of old people's erythrocyte sedimentation rate (ESR) in China. The
      reference value of healthy old people's ESR was collected according to the
      Wintrobe method, the relationship between the reference value of old people's ESR
      and altitude was tested in this paper. It was found that the reference value of
      old people's ESR decreases when the altitude gradually increases, the
      relationship is quite significant. The method of mathematical univariate
      regression analysis was used to deduce two regression equations: Y1 = 16.38 -
      0.00301X +/- 6.53, Y2 = 25.92 - 0.00438X +/- 10.25. If the altitude value of a
      particular area of China is known, the reference value of old people's ESR can be
      calculated by means of the regression equations. Furthermore, depending on the
      altitude, China can be divided into three districts: Qingzang Districts, Central
      Districts and Eastern Districts.

PMID- 11455055
TI  - In vitro-inhibition of shear-induced platelet aggregation by verapamil.
AB  - The purpose of the study was to investigate the effect of verapamil on shear
      induced platelet aggregation (SIPA). Blood of New Zealand rabbit was collected to
      prepare platelet-rich-plasma (PRP) by routine centrifugation. A cone-plate shear
      device was employed to generate shear stress. The verapamil-treated PRP or
      control PRP were sheared at 37 degrees C for 120 sec. SIPA was determined from
      counting of free platelet. The inhibition rates of SIPA by verapamil for five
      doses at three shear levels were calculated accordingly. The concentration of
      half inhibition (IC50) was 0.03, 0.07 and 0.09 mmol/l for 20, 40 and 52 dyn/cm2,
      respectively. The regression for IC50 of verapamil and shear stress follows the
      linear equation: IC50=-0.0071+0.0019tau (r=0.999,P=0.03). The results indicate
      that calcium antagonist may have the potential for inhibition of SIPA although
      the current IC50 for rabbit platelet is higher than that of human routine blood
      concentration of verapamil.

PMID- 11455056
TI  - Relevance of low titers of cryoglobulins and cold-agglutinins in patients with
      isolated Raynaud phenomenon.
AB  - INTRODUCTION: A Raynaud phenomenon can be associated with cold agglutinins or
      cryoglobulins. Although cold agglutinins or cryoglobulins may lead to severe
      acral gangrene the finding of relevant titers is rare. Low titers of cold
      agglutinins or cryoglobulins are detected more frequently but are assumed to be
      without any importance. OBJECTIVES: To prove a possible diagnostic or prognostic
      role of low titers of cold agglutinins or cryoglobulins in patients presenting an
      isolated Raynaud phenomenon we did a retrospective analysis. SETTINGS AND
      SUBJECTS: In 306 patients (40+/-16 years, range: 15-83 years) with a mean
      duration of the history of an isolated Raynaud phenomenon of 48+/-73 months we
      did a clinical examination, an analysis of antinuclear antibodies, extractable
      antibodies, cold agglutinins, cryoglobulins, plasma and blood viscosity,
      erythrocyte aggregation and a nail fold capillaroscopy. RESULTS: Low titers of
      cold agglutinins were found in 49 patients and of cryoglobulins in 7 patients.
      The finding of such low titers was not associated with extensive clinical
      symptoms, duration of clinical symptoms, megacapillaries or haemorrhagies in
      capillaroscopy, pathologic plasma and blood viscosity and erythrocyte
      aggregation. The follow-up investigations (mean: 3.1+/-1.2 years, range: 3-7
      years) revealed no development of a haematological, vasculitic or connective
      tissue disease in the subgroup of patients who only had low titers of cold
      agglutinins. CONCLUSION: The detection of low titers of cold agglutinins in
      patients with isolated Raynaud phenomenon is of no diagnostic or prognostic
      relevance.

PMID- 11455057
TI  - Hemorheological effects of sodium fluorescein in rats.
AB  - Sodium fluorescein is widely used in clinical practice for the study of the
      retinal circulation by angiography. It has been reported several hemorheological
      and microvascular abnormalities induced by this compound. The aim of this work
      was to analyse the hemorheological effects of intravenous sodium fluorescein in
      an animal model. Twenty male 10-16 weeks-old Wistar rats were used, under
      systemic anaesthesia. The animals were divided in 2 groups of 10 each: (1)
      intravenous injection of sodium fluorescein (14 mg/kg of body weight)--Group NaF,
      (2) controls (injection of NaCl 0.9%)--Group CTRL. A blood sample was drawn by
      aortic puncture after 60 minutes and hemorheological parameters determined:
      hematocrit, hemoglobin, metahemoglobin, carboxyhemoglobin, plasma viscosity,
      erythrocyte deformability, membrane fluidity and acetylcholinesterase activity.
      In the Group NaF there was a 20% reduction of the AChE activity (p<0.05) and an
      increase in PV (p<0.05). Concerning hemoglobin status, a three-fold increase in
      COHb (p<0.001) was shown. In conclusion, the NaF injection in the animal model
      produces hemorheological abnormalities similar to those reported in the human.

PMID- 11455058
TI  - Peripheral microcirculation during pregnancy and in women with pregnancy induced
      hypertension.
AB  - During pregnancy the cardiovascular system undergoes several changes so as to
      adapt the maternal organism to the strains of pregnancy. These adaptations can
      assume a pathological development in persons with a previous history of
      cardiovascular problems. On the other hand the absence of these adaptations may
      lead to a pathological course of pregnancy. Pregnancy induced hypertension (PIH)
      may be such a pathological development due to maladaptation. The causes are for
      the most part unknown. For some time it has been assumed that it is due to
      microcirculatory disorders. Using periungual capillary microscopy the present
      study prospectively investigated the changes in peripheral microcirculation
      during pregnancy focussing on pregnancy induced hypertension. Sixty-seven women
      with a normal course of pregnancy and 28 women with pregnancy induced
      hypertension were evaluated. Throughout the prospective study 3 examinations were
      performed during pregnancy and one during childbed. The women who developed a PIH
      were registered during the third trimester. Erythrocyte velocity at rest and
      vascular reagibility of capillaries following a 3 minute ischaemia were
      evaluated. In the course of pregnancy a significant increase of approximately 30%
      in erythrocyte velocity could be observed. Interpolation to obtain the best
      strait line result demonstrates that it is a continuous increase. Erythrocyte
      velocity returns to normal in the course of 14 weeks post partum. Due to a
      physiological vasodilatation during pregnancy, vascular reaction to ischaemic
      stress significantly decreases. During childbed these changes return to normal.
      Examinations on women with pregnancy induced hypertension not only showed a
      significant reduction of microcirculation under resting conditions but also a
      different pattern of reaction to ischaemic stress. Erythrocyte velocity under
      resting conditions lies 36% below normal values. Furthermore the distinctly
      shortened hyperaemic period indicates a hightened sensitivity to vasoconstrictive
      substances in women with PIH. While taking into account the clinical data a
      positive correlation with the severity of the illness was able to be established.

PMID- 11455059
TI  - Exercise increases soluble adhesion molecules ICAM-1 and VCAM-1 in patients with
      intermittent claudication.
AB  - Adhesion molecules play a relevant role in the pathogenesis of vascular diseases.
      In 21 patients with intermittent claudication and 18 sex- and age-matched control
      subjects, we measured plasma levels of the circulating form of the adhesion
      molecules E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 (VCAM-1) alongside von Willebrand factor (vWF),
      at rest, at maximally tolerated exercise and 5, 15 and 30 min after exercise. In
      controls, plasma sICAM-1 levels did not change with exercise, while in
      claudicants they increased from 285+/-15 to 317+/-16 ng/ml (p<0.01). Also for
      sVCAM-1 exercise did not modify plasma levels of sVCAM-1 in controls but
      increased it in claudicants from 671+/-45 to 751+/-47 ng/ml (p<0.05). Similarly,
      vWF did not change with exercise in controls, but increased in claudicants from
      100+/-9% to 111+/-8% of value for pooled normal plasma (p<0.05). Exercise-induced
      changes in sICAM-1 negatively correlated with the maximal tolerated walking time,
      which is an index of disease severity. These findings indicate that, in
      claudicants, exercise is associated with increase in plasma levels of sICAM-1 and
      sVCAM-1.

PMID- 11455060
TI  - Effects of an angelica extract on human erythrocyte aggregation, deformation and
      osmotic fragility.
AB  - In Chinese traditional medicine, angelica is widely used for its known clinical
      effects of ameliorating blood microcirculation. But the mechanism of these
      beneficial effects still remains unclear. In this work the rheological behaviour
      of human erythrocytes treated by angelica was studied in vitro. Normal RBCs
      incubated with an angelica extract at different concentrations (5, 10 or 20
      mg/ml) for 60 min at 37 degrees C and then their aggregation, deformation and
      osmotic fragility were measured with different recently developed optical
      techniques, namely Erythroaggregometer (Regulest, Florange, France), LORCA
      (Mechatronics, Amsterdam) and Fragilimeter (Regulest, Florange, France).
      Experimental results show that angelica (20 mg/ml) significantly decreased normal
      RBCs' aggregation speed (p<0.01) and could inhibit the hyperaggregability caused
      by dextran 500. However, the strength of normal RBCs aggregates were not
      influenced by angelica. When a calcium ionophore A23187 (1.9 microM) was used to
      harden cell membrane, angelica (20 mg/ml) could significantly (p<0.01) protect
      erythrocytes against the loss of their deformability even it had no effects on
      normal RBCs deformation. Finally angelica (5 and 10 mg/ml) decreased
      significantly (p<0.01) normal RBCs osmotic fragility. In conclusion angelica
      plays a rheologically active role on human erythrocytes, and this study suggests
      a possible mechanism for angelica's positive effects against certain
      cardiovascular diseases.

PMID- 11455061
TI  - A recombinant IgG3-(IL-2) fusion protein for the treatment of human HER2/neu
      expressing tumors.
AB  - Anti-HER2/neu therapy of human HER2/neu expressing malignancies such as breast
      cancer has shown only partial success in clinical trials. To expand the clinical
      potential of this approach, we have genetically engineered an anti-HER2/neu human
      IgG3 fusion protein containing interleukin-2 (IL-2) fused at its carboxyl
      terminus. Anti-Her2/neu IgG3-(IL-2) retained antibody and cytokine related
      activity. Treatment of immunocompentent mice with this antibody fusion protein
      resulted in significant retardation in the subcutaneous (s.c.) growth of CT26
      HER2/neu tumors suggesting that anti-HER2/neu IgG3-(IL-2) fusion protein will be
      useful in the treatment of HER2/neu expressing tumors. We also found that fusing
      IL-2 to human IgG3 results in a significant enhancement of the murine anti-human
      antibody (MAHA) response.

PMID- 11455062
TI  - Introduction.

PMID- 11455063
TI  - An overview of pain problems associated with lesions, disorder or dysfunction of
      the central nervous system.
AB  - This paper will present an overview of pain problems associated with lesions,
      disorder or dysfunction of the central nervous system (CNS). The incidence,
      qualities of the pain experience, associated sensory abnormalities, and other
      characteristics will be discussed. Particular attention will be paid to central
      pain (CP) associated with stroke as the most prominent and best studied of the
      many CP problems. In general, there is poor understanding of the pathophysiology
      of CP, problems are often severe and intractable, and treatment is typically
      difficult. The concept of CP is increasingly being invoked to account for various
      presentations not traditionally considered, e.g. fibromyalgia. It is suggested
      that processes associated with CP might also contribute to the presentation in
      psychiatric Pain Disorders or other atypical pain problems. Finally, although
      perhaps not as problematic, a number of CNS disorders or lesions may be
      associated with reduced sensitivity to pain.

PMID- 11455064
TI  - Neuropathic pain: Review of mechanisms and pharmacologic management.
AB  - Neuropathic pain is a challenge for clinicians because it is resistant to
      commonly prescribed analgesics, such as opioids and nonsteroidal antiinflammatory
      drugs. Fortunately, adjuvant analgesics, drugs not typically thought of as pain
      relievers, may be effective. It is helpful to classify adjuvant analgesics used
      to treat neuropathic pain into two broad categories: (1) membrane stabilizing
      agents, which inhibit ectopic discharges on damaged neural membranes, and (2)
      drugs that enhance dorsal horn inhibition, which may augment biogenic amine or
      GABAergic mechanisms in the dorsal horn of the spinal cord. Current evidence
      regarding efficacy generally does not support the use of one drug over another,
      and selection of a particular drug may depend on experience or expected side
      effects. The overall efficacy of tricyclic antidepressants for neuropathic pain
      is modest, and they may produce intolerable side effects. Based on current
      studies, gabapentin is a reasonable alternative to antidepressants, as initial
      monotherapy or add-on treatment, particularly for painful diabetic peripheral
      neuropathy and postherpetic neuralgia. From a practical standpoint, to optimize
      analgesia more than one drug may be necessary. Although polypharmacy is the
      result, this approach may improve therapy and minimize side effects. From a
      safety standpoint, medications generally should be started at low doses and
      titrated to effect. Although labor-intensive, this strategy can improve
      compliance and optimize patient care.

PMID- 11455065
TI  - Neurosensitization: A model for persistent disability in chronic pain,
      depression, and posttraumatic stress disorder following injury.
AB  - A neurosensitization syndrome (NSS) is defined as: a syndrome of subjective
      discomfort and objective functional disability; that often appears excessive in
      duration and severity with respect to the identified initiating injury or event;
      that may be resistant to conventional medical and psychological treatment
      modalities; and that is hypothesized to develop as the result of progressively
      enhanced sensitivity or reactivity of central nervous system (CNS) mechanisms at
      the neurophysiological, biochemical, and intracellular levels. This paper applies
      the neurosensitization model to the three syndromes which are frequently comorbid
      and treatment-refractory in clinical practice: (1) chronic pain; (2) depression;
      and (3) posttraumatic stress disorder. The understanding of how pathological
      behavioral syndromes spiral out of control may lead to productive, integrative
      medical, behavioral, and psychotherapeutic treatment strategies.

PMID- 11455066
TI  - The role of citicholine in neuropsychological training after traumatic brain
      injury.
AB  - Objective: To report new strategies in the treatment of persistent memory
      deficits following traumatic brain injury (TBI) using a combination of
      pharmacology and neuropsychological training. Study design: Two studies were
      carried out. The first study measured the regional cerebral blood flow (rCBF) of
      seven Patients with TBI with very severe memory deficits, once while resting and
      once one hour after the administration of citicholine (CDPc). In the second
      study, two groups of five patients of the same characteristics underwent an
      ecological neuropsychological memory rehabilitation program; during which time,
      one group was administered a placebo (Group A), and the other received CDPc
      (1~g/d v.o.) (Group B). Results: The results of Experiment 1 showed a
      hypoperfusion of the inferior left temporal cerebral blood flow during rest state
      while an induced normalization was observed after administration of the drug.
      Results of Experiment 2 showed no improvements in Group A's neuropsychological
      functions, while memory, learning processes and verbal fluency of Group B
      improved significantly after treatment. Conclusions: CDP-choline seems to be a
      drug with special affinity for cerebral areas associated with memory acting just
      where needed, normalizing blood flow in the hypoperfused left temporo-basal
      region, and making neuropsychological training effective. In general, data
      suggests that cognitive rehabilitation would follow the principle of first
      restoring and maintaining cerebral blood flow in the lesional site and then
      exercising function. In this study on memory rehabilitation, memory recuperation
      was made possible by first normalizing blood flow at the lesional site and at the
      same time applying neuropsychological training.

PMID- 11455067
TI  - Laws of the House of Rehab II: Practice fundamentals for improving therapeutic
      relationships and outcomes.
AB  - Interdisciplinary rehabilitation can be a complex, challenging, and sometimes
      confusing process. The varying experiences and perspectives of patients and
      professionals contribute to the diversity of challenging dilemmas. This
      manuscript is intended to help rehabilitation professionals improve their
      effectiveness and the quality of their relationships with patients, family
      members, and colleagues. The manuscript complements a prior publication, Laws of
      the House of Rehab: A Guide to Managing Psychological Distress and Promoting
      Benefit from Rehabilitation [2]. The authors have included additional information
      relating to principles of rehabilitation practice. The principles, labeled as
      "laws", provide guidance for developing values and practice methods.

PMID- 11455068
TI  - Introduction.

PMID- 11455069
TI  - At the crossroads: Pain in the 21st century.
AB  - This paper, written from the perspective of a psychologist working in a tertiary
      care chronic pain program, presents an overview of chronic pain with suggestions
      as to what may be important directions for research and treatment in the future.
      It is suggested that the monumental problem of chronic pain needs to be better
      appreciated, that both biological and psychosocial factors contributing to
      presentation need to be better understood, and that the most fruitful avenue of
      research may be an exploration of the interface between psychosocial and
      biological components, i.e., the neurobiological substrate mediating
      psychological effects or the nature of brain-behavior relationships involved in
      chronic pain. A method to assist in the differentiation of central from
      peripheral and organic from psychosocial components, and the outline of a novel
      neuropsychobiological model are described.

PMID- 11455070
TI  - Psychological assessment of persons with chronic pain.
AB  - Chronic pain is one of the most prevalent and costly health care problems and
      variability is the rule more than the exception in terms of pain related
      outcomes. Clearly, psychological factors such as depression, anxiety, post
      traumatic stress, excessive somatic thoughts and a variety of psychiatric
      syndromes are recognized as actively contributing to a patient's perceptions and
      responses to pain and can represent significant potential impediments to
      functioning and optimal health care outcome. As a result, it is becoming
      increasingly common, and even required by many programs, for individuals who seek
      treatment for pain to undergo a comprehensive assessment that evaluates not only
      their medical findings, but also beliefs about their condition, coping
      strategies, psychological adjustment, activity level and quality of life.
      Psychological assessment instruments that provide information about a person's
      physiological, behavioral, and cognitive-affective functioning in terms of
      vulnerabilities and strengths can be a valuable tool for treatment providers. In
      the present paper, a biopsychosocial conceptual model is employed to provide an
      overview of a method and approach in evaluating patients with chronic pain,
      toward the goal of facilitating optimal outcome and management of pain syndromes.

PMID- 11455071
TI  - The use of cranial electrotherapy stimulation in the management of chronic pain:
      A review.
AB  - Cranial Electrotherapy Stimulation (CES) has a growing history of applications in
      rehabilitation medicine in the United States dating back to early 1970. As a
      recognized non-drug treatment of anxiety, depression and insomnia, CES gained its
      first major application in the field of addiction treatment and rehabilitation.
      By the mid 1980s research was showing additional important uses of CES in the
      treatment of closed head injured patients, and in paraplegic and quadriplegic
      patients. The most recent research is showing CES to be highly effective in the
      management of chronic pain patients. It may be elevating the pain threshold due
      to its stress reducing effects when anxiety and depression are reduced below
      clinical levels. Modern theorists of a pain neuromatrix in the cerebral cortex
      may provide an additional basis for understanding CES mechanisms in the control
      of pain related disorders.

PMID- 11455072
TI  - Pain, cognition and traumatic brain injury.
AB  - There has been considerable controversy concerning the problem of the persisting
      post-concussive syndrome and whether cognitive or other sequelae might be
      attributed to the effects of brain injury or other causes. Headache is the
      predominant problem in virtually all surveys of the post-concussive syndrome. It
      is suggested that pain and related problems may account for most of the
      difficulties in those presenting with the persisting post-concussive syndrome or
      other cases in which mild to moderate brain injury is suspected. A survey of the
      literature concerning the relationship of pain, cognition and traumatic brain
      injury indicates that cognitive difficulties are common in acute or chronic pain,
      with or without any indication of brain injury. However, numerous methodological
      problems are apparent and there is clearly need for further study. Consideration
      is given both to psychosocial and neurobiological effects underlying any such
      relationships.

PMID- 11455074
TI  - Introduction.

PMID- 11455073
TI  - A brief introductory guide to chronic pain resources on the Internet.
AB  - The expanding Internet has become an increasingly valuable tool for world wide
      sharing of information. Health care professionals, patients, lay persons, family
      members and others are afforded instant access to masses of information and
      almost unlimited resources on virtually any topic, as well as an almost seamless
      vehicle for communication. This new medium offers tremendous implications for
      health care. However, the absence of a single clearinghouse, a single search
      procedure or guarantee of accuracy often make information access efforts
      challenging, confusing and frustrating. The present paper provides a brief
      introduction aimed at increasing appreciation of the Internet and enhancing its
      utility with regard to chronic pain and its management and offers rudimentary
      guidelines for efficient accessing of information. Finally, it presents the
      results of a comprehensive search including nearly 200 useful Internet web links
      for professionals, patients, family members and other interested persons who
      assess, treat or cope with chronic pain. Identified resources include numerous
      organizations, medical, psychological assessment and practical treatment
      strategies, assessment and treatment reviews, support groups, list serve groups
      for patients and professionals, advocacy resources, news and assistive technology
      resources. Special emphasis is given to useful resources to assist professionals
      treating persons with chronic pain, as well as resources that can assist persons
      challenged by chronic pain.

PMID- 11455075
TI  - Chronic pain in neurorehabilitation populations: Prevalence, severity and impact.
AB  - Extensive data document the adverse impact chronic pain can have on physical and
      psychosocial functioning. However, only recently has chronic pain received
      attention as a secondary complication in neurorehabilitation populations such as
      spinal cord injury, multiple sclerosis, and cerebral palsy. It is not
      unreasonable to expect that chronic pain might exacerbate impairments already
      present due to a chronic, disabling condition. The current paper reviews what is
      known about the prevalence, severity, and psychosocial impact of chronic pain in
      neurorehabilitation populations. Although there is variation among different
      conditions, available data suggest that considerable proportions of these patient
      populations experience chronic pain and associated sequelae similar to that
      reported in the extant chronic pain literature (e.g., psychological distress).
      Research needs to continue investigating the impact of chronic pain in
      neurorehabilitation populations and work toward development of effective
      interventions to manage pain and disability in these patients. It is likely that
      effective pain management will lead to more effective rehabilitation and improved
      quality of life.

PMID- 11455076
TI  - Evaluation of a test battery for hemineglect in elderly stroke patients for use
      by therapists in clinical practice.
AB  - Hemineglect is not a single entity, and the syndrome has a number of sensory and
      motor manifestations. The purpose of this study was a) to measure performance of
      healthy elderly subjects on a battery of validated tests for hemineglect in order
      to establish appropriate cut-off scores and b) to assess performance of a large
      sample of elderly stroke patients in a rehabilitation unit, using the same
      battery. Tests were selected to identify rate of occurrence of hemineglect in
      visuo-spatial, representational, pre-motor and personal modalities. The battery
      was administered to 107 patients with right or left sided brain damage and 43 age
      matched controls. Results showed that 39.2% right-sided brain damage), were
      'neglecters', scoring below cut-off in one or more tests. Star Cancellation and
      Line Bisection showed the highest relative sensitivity for visuo-spatial neglect
      (76.4%) 'Baking Tray Task', the 'Exploratory Motor Task', and utilisation of
      common objects test for personal neglect are additionally suggested for use in
      the clinical situation. 'Copying a Daisy' and clock-drawing are not recommended
      due to low sensitivity and subjectivity in scoring respectively.

PMID- 11455077
TI  - Validation of the Service Obstacles Scale for the traumatic brain injury
      population.
AB  - Traumatic brain injury is a leading cause of death and disability in the United
      States. Limited access to specialized medical and rehabilitation services has
      been linked to poor outcomes. Literature provides little guidance for assessment
      of service obstacles and satisfaction with community resources. The present
      investigation describes the development of a specialized scale to evaluate
      caregivers' perceptions of brain injury services in the community. Results
      indicate good internal consistency and criterion-related validity of the Service
      Obstacles Scale. Lack of money for services and lack of adequate community
      resources were the greatest concerns voiced by respondents, while lack of
      transportation was the least problematic. Comparisons are made with regard to
      family needs and respondents' post-injury life quality. Implications for future
      research are discussed.

PMID- 11455078
TI  - Effects of overloading of the lower hemiparetic extremity on walking speed in
      chronic stroke patients: A pilot study.
AB  - The objective of this pilot study was to investigate the carry-over effects on
      comfortable walking speed after overloading the lower hemiparetic extremity in
      chronic stroke patients. A single subject research study was conducted using a
      withdrawal design (A-B-A-B-A) on three patients with ischaemic middle cerebral
      artery infarction. Chronic stroke patients were recruited with stage 3 or 4 Fugl
      Meyer scores in the lower extremity and the ability to ambulate independently
      without walking aids. Based on this withdrawal design, the daily procedure
      included walking at comfortable speeds 5x10 meters during the A_1 phase and 3x10
      meters during all subsequent phases. This procedure was repeated for five
      consecutive days. Two lbs (B_1) and 6 lbs (B_2) weight cuffs were attached to the
      distal lower hemiparetic extremity and randomized over the two B phases. Control
      (A_1, A_2, A_3) and intervention (B_1, B_2) phases were alternated with brief
      resting periods. Mean comfortable walking speed for 10 meters constituted the
      outcome variable. All patients showed significant differences between phases
      (chi^2 = 34.187; p<0.001). However, with the exception of a carry-over effect
      between the A_1 (0.86 m/sec) and A_2 (0.89~m/sec) phases in one subject (p=0.043)
      no significant carry-over effects were found on ensuing A_2 and A_3 control
      phases. Although gradual improvements in comfortable walking speed between
      subsequent days were found the present pilot study did not demonstrate favorable
      group effects on comfortable walking speed as a result of limb overloading.

PMID- 11455080
TI  - Introduction.

PMID- 11455079
TI  - The effects of a balance and strength training program on equilibrium in
      Parkinsonism: A preliminary study.
AB  - The purpose of this study was to determine if a balance and strength training
      program could improve equilibrium and strength in persons with stage I-III
      Parkinsonism. Subjects were pre-tested on strength and balance (EquiTest) and
      randomized into either a treatment or a control group. The treatment subjects
      participated in 10 weeks of lower limb strength training and balance exercises
      designed to challenge a stable posture and increase limits of stability. Both
      groups were then posttested on balance, knee flexion, knee extension, and ankle
      inversion strength. Subjects who received strength and balance training
      demonstrated significantly improved equilibrium and modest gains in knee flexion
      and extension strength, while the control group showed no improvement in
      conditions of destabilizing balance environments and significant declines in
      strength. Results indicate that 10 weeks of balance and strength training lead to
      improved equilibrium by producing positive changes in two different control
      mechanisms. One, training altered the ability to control the motor system when
      vestibular cues had to be the primary source of reliable feedback; and two,
      training helped subjects to override faulty proprioceptive feedback and utilize
      reliable visual or vestibular cues.

PMID- 11455081
TI  - Evaluation and treatment of balance in the elderly: A review of the efficacy of
      the Berg Balance Test and Tai Chi Quan.
AB  - The purpose of this review of outcome studies was to determine whether the Berg
      Balance Test (BBT) can be considered a reliable predictor of a risk for falls in
      the elderly, and to review the efficacy of Tai Chi Quan in the physical therapy
      intervention of balance disorders in older adults as reported in the literature.
      The authors examined studies of the BBT, which showed that the two groups of
      people, fallers and non-fallers, have considerable differences among them.
      Fallers tended to be more variable in their characteristics as indicated by
      larger standard deviations. Based on these results, the authors suggest that
      patients who score high on the BBT should not be referred for further
      intervention, whereas patients who score 40 or less have a high probability of
      falls and require appropriate referrals. The BBT, which is relatively safe and
      simple, uses a quantitative scale, scoring is reproducible, and the strong
      internal consistency allows for easy interpretation of scores. The BBT has been
      shown to have moderately good sensitivity, and high specificity, and therefore is
      a good predictor of older adults who may have fall risks and may need assistive
      devices. A big challenge, then, is to plan and implement an effective treatment
      technique to improve balance control. One recently identified intervention is Tai
      Chi Quan. Tai Chi is an ancient form of exercise for fitness and the martial arts
      which has been practiced in China for centuries. The second part of this report
      examines the efficacy of Tai Chi Quan as a treatment modality. A review of
      studies on Tai Chi Quan indicates that it has a positive effect on improving
      balance in the elderly, although it has no effect on improving postural
      stability. The effects of Tai Chi on the treatment of balance still require
      extensive research. Although the articles reviewed indicate that Tai Chi does
      have a positive effect on balance, the methodology used in these studies needs to
      be improved.

PMID- 11455082
TI  - Understanding awareness deficits following brain injury.
AB  - The critical role that awareness deficits play in contributing to rehabilitation
      outcome and independent functioning of brain injured adults is readily
      acknowledged by rehabilitation professionals. However, there are inconsistencies
      in the scope of what is included within the concept of awareness and the way in
      which it is measured within the literature. A comprehensive model of awareness is
      needed to guide the development of measurement tools and interventions. This
      paper expands upon concepts originally proposed by Crosson and colleagues [12]
      and proposes a comprehensive model of awareness that integrates parallel themes
      in cognitive psychology, social psychology and neuropsychology. It argues that a
      hierarchical view of awareness does not capture the complexities and subtleties
      of awareness symptoms and proposes a dynamic relationship between knowledge,
      beliefs, task demands and context of a situation. A distinction between knowledge
      and awareness, that one has prior to a task, and that, which is activated during
      task performance, is emphasized. Suggestions for expanding assessment and
      intervention methodology are derived from the perspective of research within the
      areas of metacognition and self-efficacy.

PMID- 11455083
TI  - Return to work for individuals with TBI and a history of substance abuse.
AB  - The highest incidence of TBI is among young adult males who also have the highest
      incidence of substance abuse [1]. Since these individuals have long life
      expectancies, it is important that they are productive post injury; however, the
      employment rate is extremely low. This is understandable, given the fact that a
      person with either a TBI or substance abuse disorder would have difficulties with
      work. Naturally, the combination of the two compounds the problem and further
      complicates matters. This article provides an overview of how a Supported
      Employment approach can be used to assist persons with a TBI and substance abuse
      problems with returning to work.

PMID- 11455085
TI  - Introduction.

PMID- 11455084
TI  - Use of a novel contingency stimulator in Unilateral Spatial Neglect.
AB  - The trial of a treatment device for Unilateral Spatial Neglect (USN) is reported.
      A patient who had suffered a right hemisphere stroke that resulted in left sided
      neglect was studied over a six month period. The study involved the use of a
      customized electrical device providing stimulation to the neglected hand,
      triggered by movement of the unaffected side. A battery of neglect measures were
      performed regularly throughout the study period. Though the results were
      difficult to interpret, there was no conclusive evidence that the device was
      effective. The possible reasons for this, the methodological difficulties
      inherent in studies of this type and suggestions for further studies are
      discussed.

PMID- 11455086
TI  - The method of assisted ejaculation affects the outcome of semen quality studies
      in men with spinal cord injury: A review.
AB  - The methods of penile vibratory stimulation (PVS) and rectal probe
      electroejaculation (EEJ) are widely used to obtain semen from anejaculatory men
      with spinal cord injury. This paper reviews evidence that the semen quality
      resulting from PVS versus EEJ is different, and these methods should be used as
      variables in studies of men with spinal cord injury. The following evidence is
      reviewed. PVS and EEJ stimulate ejaculation by different mechanisms. In humans
      and monkeys, semen quality is different when obtained by PVS versus EEJ of the
      same group of subjects. In neurologically intact men, EEJ results in low sperm
      motility. Markers of accessory gland function are different in ejaculates
      obtained by PVS versus EEJ. For scientific studies, it is recommended that
      whenever possible, antegrade specimens obtained by PVS be used. For clinical
      applications, such as obtaining sperm for assisted reproductive procedures, the
      choice is less critical, however, PVS offers advantages over EEJ.

PMID- 11455087
TI  - Clinical assessment of sildenafil in the treatment of neurogenic male sexual
      dysfunction: After the hype.
AB  - Objective: To evaluate the efficacy and safety of sildenafil over a two-year
      period in patients with erectile dysfunction caused by spinal cord injury and
      multiple sclerosis in a clinical practice following FDA approval and release of
      the medication to the general healthcare community. Study design: 40 patients
      including 33 SCI (13 quadriplegics, 20 paraplegics; 14 complete, 19 incomplete)
      and 7 MS patients were prescribed sildenafil in varying dosages. The patients
      were asked to return to the clinic for additional prescriptions so that we could
      assess their clinical response and their incidence of side effects. They were
      then followed for a period of up to two years either by follow up clinic visits
      or telephone interviews to determine whether they continued to use sildenafil as
      an ongoing solution to their erectile dysfunction. Results: Mean erectile
      response went from 4.9 to 7.8 (scale 1--10). Non-responders went from 9 to 4. 36
      of the 40 were able to achieve erections sufficient for sexual intercourse. At
      the 2-year interval 13 of the 40 were no longer using sildenafil but only six
      discontinued due to lack of response. Adverse effects were minimal and mimicked
      those seen in the able-bodied studies. Conclusion: Sildenafil is a safe and
      effective first line treatment for the treatment of male neurogenic erectile
      dysfunction. However close clinical surveillance is necessary so that patients
      can avail themselves of other options should sildenafil not be effective.

PMID- 11455088
TI  - Sexual dysfunction after traumatic brain injury.
AB  - Objective: The frequency of self reported sexual difficulties was examined in a
      group of 322 individuals with traumatic brain injury (TBI) ($N = 193$ men; 129
      women) and contrasted with reports of sexual difficulties in 264 individuals
      without disability (152 men; 112 women) residing in the community. Physiological,
      physical, and body images problems impacting sexual functioning were examined
      individually and then summed into a sexual dysfunction score. Mood, quality of
      life, health status and presence of an endocrine disorder were examined as
      predictors of sexual difficulties post TBI. Study design: In this retrospective
      study, data about sexual difficulties were analyzed separately for men and women
      with TBI and without disability. ANOVAs with post hoc analysis for continuous
      variables, chi-square analyses for categorical variables, and ANCOVAs for
      predictors of sexual difficulties were utilized. Results: When contrasted to
      individuals without disability, individuals with TBI reported more frequent: (1)
      physiological difficulties influencing their energy for sex, sex drive, ability
      to initiate sexual activities and achieve orgasm; (2) physical difficulties
      influencing body positioning, body movement and sensation, and (3) body image
      difficulties influencing feelings of attractive and comfort with having a partner
      view one's body during sexual activity. Additional gender specific TBI findings
      were observed. In comparison to gender matched groups without disability, men
      with TBI reported less frequent involvement in sexual activity and relationships,
      and more frequent difficulties in sustaining an erection; women with TBI reported
      more frequent difficulties in sexual arousal, pain with sex, masturbation and
      vaginal lubrication. While groups differed in core demographic variables, age was
      the only demographic variable that was related to reports of sexual difficulties
      in individuals with TBI and men without disability. Age at onset and severity of
      injury were negatively related to reports of sexual difficulties in individuals
      with TBI. In men with TBI and without disability, the most sensitive predictor of
      sexual dysfunction was level of depression. For women without disability, an
      endocrine disorder was the most sensitive predictor of sexual dysfunction. For
      women with TBI, an endocrine disorder and level depression combined were the most
      sensitive predictors of sexual difficulties. Conclusion: Individuals post TBI
      report frequent physiological, physical and body images difficulties which
      negatively impact sexual activity and interest. For men post TBI, predictors of
      sexual difficulties included age at interview, age at injury, and having milder
      injuries, however, depression was the most sensitive predictor of sexual
      dysfunctions. For women post TBI, predictors of their sexual difficulties
      included age at injury and having milder injuries, however, depression and an
      endocrine disorder combined were the most sensitive predictors of sexual
      dysfunction. Implications of this study include the need for broad-based
      assessment of sexual dysfunction, and the implementation of treatment studies to
      enhance sexual functioning post TBI.

PMID- 11455089
TI  - Sexual expression following spinal cord injury.
AB  - Sexual adjustment, defined within this study as post-injury sexual views of the
      self, among 109 men and 86 women with spinal cord injury (SCI) was explored
      through cognitive adaptation theory [30]. It was predicted that cognitive
      adaptation constructs (i.e., personal control, optimism, meaning, and self
      esteem) and sexual self-esteem would be predictive of sexual adjustment. It was
      also hypothesized that sexual self-esteem would be predictive of sexual
      adjustment over and above cognitive adaptation constructs. A series of
      hierarchical regression models were performed with results being consistent with
      proposed hypotheses. Implications for rehabilitation professionals are discussed
      and clinical suggestions are provided.

PMID- 11455090
TI  - The neural control of female sexual function.
AB  - Recent basic research on the neural control of female sexual function is reviewed
      with an emphasis on the pathways controlling the genitalia. Sexual responses
      require the coordination of sympathetic, parasympathetic and somatic nervous
      system. This coordination is performed by interneuronal systems within the lower
      spinal cord. Sexual responses can be reflexively elicited by genital stimulation.
      The excitability of the spinal cord can be positively or negatively modulated by
      descending pathways from supraspinal sites. These supraspinal areas are
      extensively interconnected and also receive pelvic sensory information. Several
      of them are modulated by gonadal hormones, allowing for a hormonal control of
      sexual behavior. Successful restoration of function following neural injury
      requires an understanding of these neural pathways.

PMID- 11455091
TI  - A controlled trial of positive feedback to increase sexual arousal in women with
      spinal cord injuries.

PMID- 11455092
TI  - Recovery of stroke hemiplegia through neurosurgical intervention in the chronic
      stage.
AB  - Objective: We evaluated quantitatively the further recovery from impairment and
      disability in the hemiplegic stroke survivors who required neurosurgical
      intervention, i.e. cranioplasty or ventriculoperitoneal (V-P) shunt, in chronic
      stage. Setting: Rehabilitation (RH) ward affiliated with university hospitals.
      Patients: Eleven first-ever stroke patients with hemiplegia (mean age, 56.3+/-2.5
      years) out of 498 survivors required delayed (between 4 and 10 months after the
      onset) neurosurgical intervention during continuous RH therapy. Six patients
      received cranioplasty for preexisting hemicraniectomy, and five required V-P
      shunt for normal pressure hydrocephalus with later complications. Main outcome
      measures: Recovery grade (1--12) of hemiplegia and Barthel index were assessed
      monthly before (the 1st RH) and after the intervention (the 2nd RH). Results: The
      recovery grade of upper and lower extremity movements significantly increased
      both in the 1st and 2nd RH. Changes in the upper and lower extremity grades were
      significantly larger in the 2nd RH (0.5+/-0.3 in the 1st vs. 2.5+/-0.6 in the 2nd
      RH for upper extremity, p<0.005; 0.9+/-0.3 in the 1st vs. 3.4+/-0.5 in the 2nd RH
      for lower extremity, p<0.001). Barthel index increased significantly only in the
      2nd RH (from 48+/-7 to 90+/-3, p<0.001); all patients regained the ability to
      walk independently. Conclusions: Significant recovery of functional grade and
      recovery from disability occurred after the neurosurgical intervention in the
      chronic stage (geq 4 months) of stroke.

PMID- 11455093
TI  - Prenatal infarction of the left middle cerebral artery: A case report of
      excellent functional outcome.
AB  - Extensive cortical-subcortical damage of the left hemisphere, most likely due to
      prenatal infarction of the left middle cerebral artery, was accidentally detected
      in a 12-year-old left-handed girl. Since clinical symptoms were minimal, the
      lesion had not been discovered for more than a decade. Meticulous examination
      revealed some slowness and somatosensory deficits of the right hand. Yet,
      independent finger movements were preserved, and functional skills such as
      reaching and grasping were unimpaired, as documented with optoelectronic motion
      analysis. There were no mirror movements. Transcranial magnetic stimulation
      indicated that the right hand was controlled by spared cortical areas of the
      damaged hemisphere. Gait was normal. Neuropsychological examination confirmed
      regular development of language, intellect, and visuospatial abilities. This case
      report demonstrates exceptionally good functional outcome after early brain
      damage.

PMID- 11455094
TI  - Vocational outcomes for persons with severe physical disabilities: Design and
      implementation of workplace supports.
AB  - Clearly, the need for a skilled labor pool is great in today's economy. Yet, many
      people with significant disabilities are struggling to find jobs with the
      majority of them unemployed or underemployed [6]. There is a need to develop
      strategies that can effectively empower these individuals to become part of the
      nation's labor force. This article describes one model project that used person
      centered career plans, supported employment, and on-the-job assistive technology
      assessment and training to assist 21 individuals to become competitively
      employed. Customers worked an average of 15.66 months earning an average of
      $7,271 in total wages. They were hired by both small and large businesses to do a
      variety of tasks to include data entry, customer service, clerical assistance, as
      well as food prep. While the findings are preliminary, the results indicate that
      individuals with severe physical disabilities can maintain employment by
      combining supported employment and assistive technology within the workplace.

PMID- 11455095
TI  - Neuropsychological change following individualized cognitive rehabilitation
      therapy.
AB  - Results from a retrospective chart review of thirty-seven patients completing an
      individualized cognitive rehabilitation therapy (CRT) program, using a
      Developmental Metacognitive approach, are reported. Neuropsychological
      functioning was used as the measure of progress in CRT. Demographic data, number
      of CRT sessions, and number of months post-injury were used to predict overall
      improvement in neuropsychological status. Eighty-nine percent of the patients in
      the CRT program experienced significant change on at least one neuropsychological
      measure administered. Despite considerable sample diversity, demographic and
      treatment variables were not predictive of overall neuropsychological change.
      Individualizing the CRT approach can maximize the chance of improvement in a
      diverse patient sample.

PMID- 11455096
TI  - Cognitive and functional status in two subtypes of vascular dementia.
AB  - In the present study we examined cognitive function, radiographic features, and
      functional ability in individuals with vascular dementia (VaD). Subjects were
      subdivided into individuals with only white matter involvement (WM) and
      individuals with evidence of a cortical infarction in addition to white matter
      ischemic change (C+WM). Results revealed that both groups of subjects were
      impaired across cognitive functions. Cognitive performance was more severely
      impaired among the C+WM group, but the general pattern of deficits did not differ
      between the two groups. Hachinski scores were significantly higher and
      instrumental activities of daily living were more severely affected in the C+WM
      group compared to the WM group. No significant differences were evident between
      the two groups on overall dementia severity or the extent of white matter
      involvement. These findings indicate that cognitive function in VaD may be
      globally impaired, and that cortical infarction in addition to white matter
      ischemia results in greater impairment, but the differences are largely
      quantitative rather than qualitative.

PMID- 11455098
TI  - Defining community integration of persons with brain injuries as acculturation: a
      Canadian perspective.
AB  - In this study, the AIMS, a measure of community integration developed from
      acculturation theory, was used to explore the various ways that people with brain
      injuries, a smaller cultural or minority group, are involved with the larger
      cultural group and to evaluate rehabilitation outcome (i.e., reintegration into
      the community). Specifically, the AIMS assesses whether the needs of individuals
      with brain injuries in a number of areas are identified and supported in a way
      that supports community participation. In addition, the opinions of persons with
      a brain injury regarding their level of community integration were compared to
      the opinions of individuals who knew them well. The results of this study
      indicate that while a large proportion of the participants with brain injuries
      were integrated in traditional areas of service delivery such as medical
      services, housing and social activity, their disability-related needs were not
      being identified and supported adequately in the areas of spirituality and
      productive activity.

PMID- 11455099
TI  - Social networks as support interventions following traumatic brain injury.
AB  - The social network and social support needs of people following traumatic brain
      injury (TBI) are considerable and related to both health outcomes and community
      integration. We review what is known of the structure of social networks
      following TBI and explore the relationship of these networks to social support
      and health. Social network interventions in TBI are described and discussed.
      Empirically based suggestions are given for the development of interventions
      based on culturally sensitive programmes which develop social networks and
      support in a naturalistic manner.

PMID- 11455100
TI  - Integration through a city-wide brain injury network and best practices project.
AB  - Integration of systems of service for individuals who have sustained a brain
      injury (BI) is critical to their successful recovery and reintegration into the
      community [6,7,33]. The Toronto Acquired Brain Injury (ABI) Network, an umbrella
      organization of 17 partners in the city of Toronto, Canada, is attempting to
      create a cost-effective, seamless, efficient, and effective integrated system of
      service. The ABI Network includes organizations and agencies along the full
      continuum, from acute care inpatient to long term care reintegration and is
      ultimately focused on helping clients achieve their goals. Through a variety of
      projects and activities, progress is being made. A significant initiative,
      currently underway, is the development of Network-wide best practices, related to
      assessment and outcomes, rooted in empirical evidence and current research. The
      project also integrates the perspectives of clients and families. The hope is
      that this initiative will result in enhanced consistency across programs,
      ensuring universal access to treatment and interventions following brain injury
      from the time of an individual's injury through integration into the community.

PMID- 11455101
TI  - Towards the development of brain injury specialists.
AB  - Brain injury presents a hugely complex, and sometimes daunting arena for the
      rehabilitation professional. With disruption to a person's core sense of self
      being almost the sine qua non of brain injury, rehabilitation can cover physical,
      psychological, social, philosophical and psychiatric realms. Those with brain
      injury can also be amongst the most vulnerable people in our society. Their
      rehabilitation has profound implications socio-politically, both in how we seek
      to understand disturbance in others, and also how we strive to ameliorate it.
      Whilst both theory and practice have grown exponentially over the last two
      decades, there is still no formal training or qualification within the brain
      injury rehabilitation field. This paper discusses the need for such formal
      training at both a theoretical and practical level not only for clinicians but
      also for front line staff, families and primary care services. The difficulties
      inherent in providing co-ordinated and structured training in such a complex area
      are discussed, and finally a model that attempts to meet user needs is outlined.

PMID- 11455102
TI  - Return to work after brain injury: a self-directed approach.
AB  - For many, returning to work after a brain injury is an extremely difficult task.
      Many factors influence a person's decision whether or not to work. While some
      people with brain injury are excited to return to their old jobs, others are
      afraid of the physical, emotional, and financial consequences of returning to
      work, and some just do not want to work at all. The following manuscript provides
      a framework for persons with brain injury to address concerns regarding returning
      to work and alternatives to living productively. There are a number of ideas
      discussed within the framework of a self-guided therapeutic return to work
      program. Clinicians are encouraged to use the information provided to facilitate
      return to work discussions with their clients with brain injury and to adapt as
      necessary for use with persons with other neurological disabilities.

PMID- 11455103
TI  - After hospital: working with schools and families to support the long term needs
      of children with brain injuries.
AB  - Medical and rehabilitation systems care for children who sustain brain injuries.
      Their much needed services, however, are short in comparison with the long term
      needs of these children and their families. For the most part, it is schools and
      families who provide the long term supports to help children make the best
      outcomes and create a better quality of life. Professionals and families who
      develop collaborative models find that they can more effectively manage services
      for these children by carefully crafting Individual Education Plans (IEP's).
      Through the IEP process students' complex needs; the multiple transitions they
      experience; and their long term needs can be met.

PMID- 11455104
TI  - Family interventions after traumatic brain injury: a service example.
AB  - Traumatic brain injury (TBI) often exerts a major impact upon the family with
      high levels of stress and distress, particularly amongst primary carers,
      disruption to family life style and functioning, changes in family roles, and
      marital and sexual difficulties. In response to the documented impact upon the
      family a range of family services have been advocated including family education,
      counselling and support. This paper outlines family services developed within a
      community head injury service in the UK. The family assessment programme
      comprises a relatives' screening questionnaire and structured interview schedules
      and ratings scales, some drawn from the family assessment literature, others
      developed within the service. Four components of family intervention are
      described: an annual series of educational workshops; follow-up workshops;
      individual family support; and specialist marital counselling. Our experience of
      providing these family services over the last 7 years is discussed along with the
      need for further evaluation of family assessment and interventions after TBI.

PMID- 11455106
TI  - Effects of gymnastics expertise on the perception of body orientation in the
      pitch dimension.
AB  - The purpose of this study was to investigate how experts in motor skills
      requiring a fine postural control perceive their body orientation with few
      gravity based sensory cues. In Experiment 1, expert gymnasts and controls had to
      detect their body tilt when pitching at a velocity of 0.05 deg.s(-1), in two
      conditions of body restriction (strapped and body cast altering the somatosensory
      cues). Contrary to the experts, the controls exhibited a larger body tilt when
      totally restrained in the body cast. In Experiment 2, subjects had to estimate
      their Subjective Postural Vertical (SPV) starting from different angles of pitch
      tilt. The controls exhibited significant errors of SPV judgement whereas the
      experts were very precise. These results suggest that 1) somatosensory cues are
      more informative than otolithic cues for the perception of body orientation, and
      2) the efficiency of otolithic and/or interoceptive inputs can be improved
      through a specific training to compensate for the lack of somatosensory cues.

PMID- 11455107
TI  - Asymmetry of ocular motor and perceptual vestibular processing in humans with
      unilateral vestibular deafferentation.
AB  - To investigate the effect of asymmetrical vestibular input on the perceived
      straight-ahead direction, we compared 7 subjects (age 59 +/- 8 yrs, mean +/- SD)
      who had chronic (>10 mos) unilateral vestibular deafferentation with 10 age
      matched controls (age 61+/-6 younger controls (age 28 +/- 7 yrs). Despite the age
      difference, the two control groups performed similarly and were therefore pooled.
      Eye and head movements were recorded using search coils as subjects underwent 30
      s trials of sinusoidal, whole body oscillation (0.4-2 Hz, peak velocities 0-120
      degrees /s) in darkness while attempting to maintain gaze on a remembered target
      5 m distant. As a control, most stimulus oscillations were randomly superimposed
      on an imperceptible, constant velocity of +/-0.5 degrees /s that produced a whole
      body offset of 15 degrees by the end of the trial. Following oscillation,
      subjects remained motionless in darkness and were asked to orient both gaze and a
      manipulandum to the remembered target location. In control subjects, mean final
      gaze and manipulandum positions were within 15 degrees of the target for all
      testing conditions. There was no dependence of final gaze and manipulandum
      positions on the frequency or velocity of the preceding whole-body oscillations
      (p > 0.05). In four of seven unilaterally deafferented subjects there was an
      ipsilesional bias of final eye position of > or =10 degrees. These subjects moved
      both eye and manipulandum to the ipsilesional side, with the error increasing at
      higher stimulus velocities. For the 120 degrees /s peak head velocity, mean
      ipsilesional gaze bias ranged from 10-37 degrees and mean manipulandum bias
      ranged from 26-108 degrees. Although the errors depended on velocity p < 0.01),
      errors were independent of frequency (p > 0.1). In the remaining three subjects
      with vestibular deafferentation, final gaze and manipulandum positions [were not
      statistically different from controls.] Early gain (eye velocity / head velocity)
      of the VOR averaged 0.82 +/- 0.01 for the first 10 s of all trials and was
      similar in all groups (p > 0.1). Gain during the final 10 s gain averaged 0.78 +/
      0.01 for control subjects, but was significantly lower at 0.70 +/- 0.01 for
      unilaterally deafferented subjects, whose eye positions reached the limit of the
      ocular motor range. We conclude that many humans with chronic unilateral
      vestibular deafferentation have a large ipsilesional dynamic bias of eye position
      and the perceived straight ahead direction reflecting persistent asymmetry of
      vestibular processing.

PMID- 11455108
TI  - Dynamics of the human linear vestibulo-ocular reflex at medium frequency and
      modification by short-term training.
AB  - We study here the effect of a short-term training paradigm on the gain and phase
      of the human translational VOR (the linear VOR: LVOR). Subjects were exposed to
      lateral sinusoidal translations on a sled, at 0.5 Hz, 0.3 g peak acceleration.
      With subjects tracking a remembered target at 1.2 m, the LVOR (slow-phase) under
      these conditions typically has a phase lead or lag, and a gain that falls short
      of compensatory. To induce short-term adaptation (training), we presented an
      earth-fixed visual scene at 1.2 m during sinusoidal translation (x 1 viewing) for
      20 minutes, so as to drive the LVOR toward compensatory phase and gain. We
      examined both the slow-phase and the saccadic responses to these stimuli. Testing
      after training showed changes in slow-component gain and phase which were mostly
      but not always in the compensatory direction. These changes were more consistent
      in naive subjects than in subjects who had previous LVOR experience. Changes in
      gain were seen with step as well as sinusoidal test stimuli; gain changes were
      not correlated with vergence changes. There was a strong correlation between gain
      changes and phase changes across subjects. Fast phases (catch-up saccades) formed
      a large component of the LVOR under our testing conditions (approximately 30% of
      the changes in gain but not in phase due to training.

PMID- 11455109
TI  - Effects of hypergravity on morphology and osteopontin expression in the rat
      otolith organs.
AB  - Recovery from balance disorders after spaceflight is supposed to reflect the
      process of readaptation to normal gravitational environment (1G) from
      microgravity. Linear acceleration including gravity is perceived by otolith
      pathways, therefore, it could be assumed that possible plastic changes in any
      part of otolithic pathways from the level of the vestibular periphery to the
      central vestibular system might be responsible for adaptive mechanisms to an
      altered gravitational environment. In the present study, to elucidate a role of
      otoconia in adaptation to altered gravity, we examined the effects of
      hypergravity (2G) on morphology and synthesis of saccular and utricular otoconia
      in young adult rats. Morphology of otoconia was examined by scanning electron
      microscopy. Otoconial synthesis was assessed by mRNA expression of osteopontin, a
      matrix protein of otoconia, in otolithic maculae as a marker of otoconial genesis
      determined by a real-time quantitative PCR method. The present results showed
      that neither otoconial morphology nor otoconial synthesis was affected by up to
      one week exposure to hypergravity. These findings suggest that changes in
      neurotransmission at the synapses of the peripheral and/or central vestibular
      system rather than the changes in otoconial morphology and synthesis may be
      involved in adaptive mechanisms to an altered gravitational environment.

PMID- 11455110
TI  - Vertical nystagmus in normal subjects: effects of head position, nicotine and
      scopolamine.
AB  - We measured gaze stability in darkness of four normal humans using the search
      coil technique. Subjects were tested first with their heads erect, and then with
      their heads positioned 180 degrees upside-down. In each position, subjects held
      their head stationary for one minute, and then actively performed pitch rotations
      for 20 sec. All subjects showed sustained chin-beating nystagmus in the upside
      down position. Each subject showed a significant increase of slow-phase velocity
      directed towards their brow after 40 sec in the inverted versus erect position.
      Pitch head rotation had little effect on subsequent nystagmus, except for
      transient reversal in one subject. The sustained changes of vertical eye drifts
      induced by 180 deg change of head position suggest that otolithic factors may
      contribute to vertical nystagmus in normals. The subjects were retested after
      wearing a nicotine patch for 2 hours. In three subjects, nicotine induced brow
      beating nystagmus; adopting a head-hanging position increased this nystagmus in
      two subjects. In a third session, subjects were tested after wearing a
      scopolamine patch for 2 hours; results were generally similar to the control
      condition. We conclude that normal subjects may show chin-beating ("downbeating")
      nystagmus in a head-hanging position in darkness, reflecting a normal,
      physiological change in otolithic inputs brought about by the head orientation.

PMID- 11455111
TI  - Idiothetic orientation and path integration in unilateral hippocampal atrophy and
      sclerosis.
AB  - We determined the effects of hippocampal lesions on idiothetic spatial
      orientation by exposing 14 patients with unilateral hippocampal atrophy and/or
      sclerosis (HAS) and 10 normal controls to random rotational displacements (+/-30
      degrees -180 degrees ) in darkness and examined their ability to rotate
      themselves back to the initial position. In comparison to controls, the patients
      responses were distinctly hypometric (p<0.005). Patients with right hippocampal
      lesions showed a trend towards higher come back errors p = 0.08). Normal controls
      could maintain their accuracy over five consecutive trials. Patients, beginning
      with less accuracy, showed significant improvement after each trial (p<0.001).
      The findings suggest that unilateral HAS impair the immediate recall of
      idiothetic spatial information, but does not affect long-term spatial learning.

PMID- 11455113
TI  - Temporomandibular disorders and hormones in women.
AB  - Temporomandibular disorders (TMD) are loosely defined as an assorted set of
      clinical conditions, characterized by pain and dysfunction of the masticatory
      system. Pain in the masticatory muscles, in the temporomandibular joint (TMJ),
      and in associated hard and soft tissues, limitation in jaw function, and sounds
      in the TMJ are common symptoms. That women make up the majority of patients
      treated for TMD is extensively hypothesized and documented in numerous
      epidemiological studies. Certain contradictory studies exist which propose that
      there are no statistically significant gender differences in the actual incidence
      of changes in joint morphology. Nonetheless, extensive literature suggests the
      disorder is 1.5-2 times more prevalent in women than in men, and that 80% of
      patients treated for TMD are women. The severity of symptoms is also related to
      the age of the patients. Pain onset tends to occur after puberty, and peaks in
      the reproductive years, with the highest prevalence occurring in women aged 20
      40, and the lowest among children, adolescents, and the elderly. The gender and
      age distribution of TMD suggests a possible link between its pathogenesis and the
      female hormonal axis. In this review, we will use the hypothesis that the
      overwhelming majority of patients treated for temporomandibular disorders are
      women and use the available literature to examine the role of hormones in TMD.

PMID- 11455114
TI  - Loading of the temporomandibular joint: anatomical and in vivo evidence from the
      bones.
AB  - 'Loading of the TMJ' is usually understood to mean a compressive force applied to
      the articular surfaces of the jaw joint. Theoretical models of jaw mechanics can
      be manipulated to support either the presence or the absence of loading,
      depending on the assumed contraction patterns of the muscles and the assumed
      occlusion. This paper synthesizes a series of studies on jaw joint function using
      pigs as substitutes for humans. Bone strain (deformation) was directly measured
      on the lateral surfaces of the condylar neck and the squamosal (equivalent to the
      human temporal) bone. Chewing strains indicate that loading does occur and is not
      light. The peak strains on the condyle are indeed primarily compressive, but the
      situation is dynamic. Small tensile strains can occur during chewing, and
      protrusive splints may decrease the strain resulting from muscle stimulation. The
      squamosal bone is even more surprising, in that the major strain is tensile. The
      most likely explanation for this finding is that the squamosal bone is bent under
      the load. Thus, the two elements of the TMJ are deformed in different ways by the
      same movements and muscle activities. Internal bony architecture reflects these
      differences. The condyle is filled with fine, vertically oriented bony
      trabeculae. The articular eminence has thick cortices and trabeculae oriented
      approximately transversely. In conclusion, the TMJ is loaded, but the situation
      is complex. The largest forces seen by the condyle are compressive, and they
      arise from muscle contraction. These same forces serve to bend the squamosal
      bone.

PMID- 11455115
TI  - Bone density, dynamic joint loading and joint degeneration. A review.
AB  - Increased joint loading and elevated bone density may be involved in the
      initiation or progression of osteoarthritis. Here, we provide an introduction to
      the literature on this topic and describe recent studies from our laboratories on
      several cohorts of subjects who had or were scheduled to have a total hip
      replacement for unilateral end-stage osteoarthritis. This population is very
      useful for studying the development and progression of osteoarthritis because of
      the known higher incidence of osteoarthritis in the contralateral hip than in a
      normal population. Separate studies of the asymptomatic contralateral hip in
      these subjects have shown that radiographic signs of early osteoarthritis are
      associated with increased bone mineral density and some of the gait adaptations
      typically found in subjects with end-stage osteoarthritis. We have also shown in
      separate studies of similar populations that elevated bone mineral density is
      associated with a subsequent accelerated joint space narrowing rate and that
      elevated hip joint loads during gait are similarly associated with an accelerated
      narrowing rate. Major questions yet to be answered are how joint loading and bone
      density interact in the development and progression of joint degeneration.

PMID- 11455116
TI  - Brief exposure to testosterone is sufficient to induce sex differences in the
      rabbit masseter muscle.
AB  - In order to evaluate whether testosterone is responsible for inducing long
      lasting sex differences in myosin heavy chain gene expression in the rabbit
      masseter muscle, we castrated young adult animals and administered supra
      physiologic doses of testosterone for 3 or 6 weeks duration. Biopsies were taken
      from the masseter muscles of these animals at the time of castration and 3, 6 and
      9 weeks later. Both immunoblot and immunohistochemical analyses of the myosin
      heavy chain (MyHC) isoform content of these muscle samples were performed.
      Exposure to testosterone for either duration resulted in a dramatic decrease in
      the content of the cardiac alpha MyHC isoform and a comparable increase in the
      content of the IIa MyHC isoform. The decrease in the cardiac alpha MyHC isoform
      content persisted for as long as 6 weeks after the end of treatment, but the
      increase in the content of the IIa MyHC isoform declined to normal during this
      time. Significant numbers of fibers were found containing both the cardiac alpha
      (and slow) and the IIa isoforms. Several fibers were encountered that contained
      both IIa and, presumably, the IIx isoform. Thus, a brief exposure to testosterone
      during postnatal maturation is able to produce a long lasting myosin heavy chain
      isoform switch that is similar in magnitude to that found during normal
      development.

PMID- 11455117
TI  - Properties of sensory neurons innervating synovial joints.
AB  - While it is clear that the TMJ joint has a sensory innervation like other
      synovial joints, there is little specific information about the function of the
      innervation of the TMJ. In order to provide a template upon which future studies
      might build, this article briefly reviews the function of sensory neurons in
      other synovial joints.

PMID- 11455118
TI  - Sex differences in brainstem neural activation after injury to the TMJ region.
AB  - The basis for a higher prevalence of painful temporomandibular disorders (TMD)
      among women than men is not known. The present study used Fos-like
      immunoreactivity (Fos-LI) to quantify the pattern and magnitude of neural
      activation within the trigeminal brainstem complex of male and female rats caused
      by acute inflammatory injury to the temporomandibular joint (TMJ) region. Also,
      Fos-LI was assessed in animals given morphine, a preferential mu opioid receptor
      agonist, or U50,488H, a selective kappa opioid agonist, prior to TMJ injury to
      determine if opioid modulation of neural activation was similar in males and
      females. The general pattern of Fos-LI after TMJ injury was similar in males and
      females. This pattern was characterized by a high density of Fos-positive neurons
      in the dorsal paratrigeminal nucleus (dPa5), subnucleus interpolaris/caudalis
      transition region (Vi/Vc-vl), and in the superficial laminae at the subnucleus
      caudalis/upper cervical spinal cord (Vc/C2) junction ipsilateral to TMJ injury.
      In contrast to other regions the number of Fos-positive neurons produced at the
      Vc/C2 junction was proportional to the concentration of mustard oil injected into
      the TMJ region. In addition, proestrus females produced higher levels of Fos-LI
      at the Vc/C2 junction than diestrus females or males. Morphine caused a greater
      dose-related reduction in Fos-LI at the dPa5 and Vc/C2 junction in males than
      females. By contrast, U50,488H caused a dose-related reduction in Fos-LI only at
      the Vc/C2 junction of proestrus females. These results support the hypothesis
      that the Vc/C2 junction region plays a critical role in the integration of pain
      signals originating from the TMJ region and may underlie sex differences in
      sensory processing related to TMJ pain.

PMID- 11455119
TI  - Orofacial deep and cutaneous tissue inflammation and trigeminal neuronal
      activation. Implications for persistent temporomandibular pain.
AB  - A rat model has been developed to characterize the responses of brainstem
      trigeminal neurons to orofacial deep and cutaneous tissue inflammation and
      hyperalgesia. Complete Freund's adjuvant (CFA) was injected unilaterally into the
      rat temporomandibular joint (TMJ) or perioral (PO) skin to produce inflammation
      in deep or cutaneous tissues, respectively. The TMJ and PO inflammation resulted
      in orofacial behavioral hyperalgesia and allodynia that peaked within 4-24 h and
      persisted for at least 2 weeks. Compared to cutaneous CFA injection, the
      injection of CFA into the TMJ produced a significantly stronger inflammation
      associated with a selective upregulation of preprodynorphin mRNA in the
      trigeminal spinal complex, an enhanced medullary dorsal horn hyperexcitability,
      and a greater trigeminal Fos protein expression, a marker of neuronal activation.
      The Fos-LI induced by TMJ inflammation persisted longer, was more intense,
      particularly in the superficial laminae, and more widespread rostrocaudally.
      Thus, the inflammatory irritant produces a stronger effect in deep than in
      cutaneous orofacial tissue. As there is heavy innervation of the TMJ by
      unmyelinated nerve endings, a strong nociceptive primary afferent barrage is
      expected following inflammation. An increase in TMJ C-fiber input after
      inflammation and strong central neuronal activation may initiate central
      hyperexcitability and contribute to persistent pain associated with
      temporomandibular disorders. Since deep inputs may be more effective in inducing
      central neuronal excitation than cutaneous inputs, greater sensory disturbances
      may occur in pain conditions involving deep tissues than in those involving
      cutaneous tissues.

PMID- 11455120
TI  - Degradative pathways in tissues of the temporomandibular joint. Use of in vitro
      and in vivo models to characterize matrix metalloproteinase and cytokine
      activity.
AB  - Identification of a small animal model that undergoes pathological
      temporomandibular joint (TMJ) degeneration would represent a significant research
      tool. To date however, no such model has been described. We therefore have
      investigated the pathological and immunohistochemical features of the TMJ of a
      transgenic mouse that over expresses the human form of TNFalpha. The TMJ of this
      animal appears to undergo changes that resemble arthriditics of temporomandibular
      dysfunction. Furthermore, the disc and articular cells express MMP9 and IL-1.
      Future work should validate this animal model as one that would have utility for
      the study of TMJ disorders. Maintenance of connective tissues in joints such as
      the TMJ is a normal process that allows for the reconstitution of important
      anatomic features. This maintenance involves both the removal and re-synthesis of
      structural proteins such as collagens, elastins and proteoglycans. An imbalance
      in the pathways for degradation and synthesis can lead to the degeneration of
      joint tissues. We describe the presence of a matrix metalloproteinase, MMP9 (92
      kD gelatinase), in TMJ disc and articular cells that likely function in the
      degradative process. Additionally, we show that this enzyme is under the control
      of pro-inflammatory cytokines whereby TGFbeta and IL-1 stimulate and PGE(2)
      inhibits its activity.

PMID- 11455121
TI  - Inflammation and bony changes at the temporomandibular joint.
AB  - Cytokines help mediate the acute and chronic inflammation and associated
      destruction of connective tissue in arthritic temporomandibular joints (TMJ). The
      proinflammatory cytokines TNFalpha, IL-1beta, IL-6, IL-8, and IFN-gamma are
      associated with inflammation in synovial joints and connective tissue
      destruction. Therefore, the increased levels of these cytokines in the synovial
      fluid of temporomandibular disorder (TMD) patients would be expected. Conversely,
      IL-1ra and IL-10 acts as inhibitors to these proinflammatory cytokines. Thus, in
      TMD patients, low levels of IL-1ra and IL-10 might be expected. A review of
      studies from multiple investigators confirms that proinflammatory cytokine levels
      increase in TMD patients, IL-1ra levels are also increased, and IL-10 levels
      remain unchanged. Because IL-10 can inhibit TNFalpha, IL-1, IL-6, and IL-8, the
      lack of IL-10 in the TMJ in the face of the other studies showing increases in
      TNFalpha, IL-1beta, IL-6, and IL-8 could partially explain the exacerbation of
      the associated osteoarthritis. In addition, although IL-1ra levels are elevated
      in most of the TMD patients, the increases do not appear to be sufficient to
      inhibit the inflammation and connective tissue degradation associated with IL
      1beta. Thus, it appears that treatment of TMD requires a delicate balance between
      proinflammatory cytokines and cytokine inhibitors such as IL-1ra and IL-10.

PMID- 11455122
TI  - Drug discovery and target validation.
AB  - Recent drug discovery has been driven largely by a genomics-based approach. This
      revolution in pharmaceutics is based on localized expression of either a novel
      gene or homologue of a known gene found in cDNA libraries made from normal versus
      diseased tissue. The choice and quality of cDNA library is critical for the
      success of this approach. Expression is normally verified at the cellular level
      by either immunocytochemistry or in situ hybridization. Activity of the
      recombinant protein in secondary cell-based assays allows highthroughput screens
      to be formulated to identify small-molecule effectors of this protein. More
      recently, a proteomics approach has also been incorporated into this process.
      This technology directly measures proteins whose expression is localized in
      disease tissue as the basis for cell-based screens to look for either activators
      or inhibitors, of this activity. The majority of screens are designed to look for
      inhibitors. Activity of small-molecules found by screening gives rise to
      pharmacokinetic studies and verification of activity in animal models of the
      disease. Structure-activity relationship (SAR) optimization of these small
      molecules allows for suitable oral bioavailability and pharmacokinetics,
      resulting in compounds progressing from discovery to development. Based on these
      strategies, we have developed inhibitors of osteoclast-mediated bone resorption
      and are currently screening for bone anabolic agents. In addition, we have also
      developed small-molecule caspase inhibitors which prevent chondrocyte apoptosis
      and retain cell function in an attempt to find therapeutic agents to either
      prevent or treat osteoarthritis. These agents may well have utility in the
      treatment of temporomandibular joint diseases.

PMID- 11455123
TI  - Photopolymerized biomaterials for application in the temporomandibular joint.
AB  - Chronic foreign body reactions have limited the successful application of
      alloplastic implants for treatment of temporomandibular joint (TMJ) disorders.
      There is a great clinical need for new materials with enhanced properties for
      application in the diarthrodial joint. Photopolymerizations may provide many
      advantages for fabricating new biomaterials for the TMJ and may address some of
      the notable differences between the TMJ and other articulations. Specifically,
      the feasibility of trans-tissue (i.e. through the skin) photopolymerizations may
      yield less-invasive surgical procedures. Also, novel 3-dimensional
      photoprocessing techniques may be used to fabricate patient-specific alloplastic
      devices for improved compliance and efficacy. Finally, the mild conditions
      necessary for photopolymerizations make the reaction ideal for encapsulating
      cells with the potential to create constructs for tissue engineering, which may
      be beneficial for disk replacement therapies.

PMID- 11455124
TI  - Bone blood flow and vascular reactivity.
AB  - Blood flow is essential for normal bone growth and bone repair. Like other
      organs, the regulation of blood flow to bone is complex and involves numerous
      physiologic mechanisms including the sympathetic nervous system, circulating
      hormones, and local metabolic factors. Our studies addressed the following
      questions: (1) Which endogenous vasoconstrictor agents regulate in vivo blood
      flow to bone? (2) Does a decrease in bone vascular reactivity to vasoconstrictor
      hormones account for the increase in blood flow during bone healing? (3) Does the
      endothelium influence bone arteriolar function? An intact bone model was
      developed in the rat to assess hormonal regulation of in vivo bone blood flow and
      in vivo bone vascular reactivity. An isolated, perfused bone arteriole
      preparation was employed to characterize the responsiveness of small resistance
      size arterioles (diameter < 100 microm) to vasoconstrictor hormones and to
      evaluate the role of the vascular endothelium to modulate vascular smooth muscle
      reactivity. Our results indicate that: (1) though exogenous endothelin is a
      potent constrictor of the in vivo bone vasculature, endogenous endothelin does
      not actively regulate in vivo blood flow; (2) the increase in blood flow to a
      bone injury site is not due to a decrease in bone vascular sensitivity to
      norepinephrine, and (3) isolated bone arterioles of young rats are very sensitive
      to vasoconstrictor hormones but exhibit only modest endothelium-mediated
      vasodilation.

PMID- 11455125
TI  - Impaired intramembranous bone formation during bone repair in the absence of
      tumor necrosis factor-alpha signaling.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is known to mediate bone resorption;
      however, its role in osteogenesis has not been fully elucidated. In order to
      investigate the direct role of TNF-alpha signaling in the recruitment and
      differentiation of osteoblasts, two separate models of bone repair were used,
      marrow ablation and simple transverse fractures. These models were carried out in
      the tibiae of both wild-type and knock-out mice in which both TNF-alpha receptors
      (p55(-/-)/p75(-/-)) had been ablated. Marrow ablation is a unique model in which
      robust intramembranous bone formation is induced without an endochondral
      component, followed by remodeling and restoration of the original trabecular
      architecture of the bone marrow. In contrast, fracture repair proceeds
      concurrently through both endochondral and intramembranous processes of new bone
      tissue formation. In both models of bone repair, healing was delayed in the TNF
      alpha receptor (p55(-/-)/p75(-/-)) deficient mice. In the marrow ablation model,
      young osteoblasts were recruited into the marrow space by day three in the wild
      type mice, while the TNF-alpha (p55(-/-)/p75(-/-)) mice had only granulation
      tissue in the marrow cavity. Type I collagen and osteocalcin mRNA expressions
      were reduced approximately 30 and approximately 50%, respectively, of the control
      values in the TNF-alpha receptor ablated mice. In the fracture repair model there
      was almost a complete absence of the initial intramembranous bone formation on
      the periosteal surface in the TNF-alpha (p55(-/-)/p75(-/-)) mice. As healing
      progressed however, the callus tissues were greatly enlarged, and there was a
      delay in hypertrophy of the chondrocytes and the resorption of cartilage tissue.
      While during the initial period of fracture repair there was a marked reduction
      in the expression of both type I collagen and osteocalcin mRNAs in the TNF-alpha
      (p55(-/-)/p75(-/-)) mice, levels of these mRNAs were elevated by approximately 10
      20% over the wild type at the later time points in the absence of endochondral
      resorption of the callus. The lack of inhibition of osteogenesis during
      endochondral resorption suggests that a different set of signals are involved in
      the recruitment of osteogenic cells during endochondral repair then during
      intramembranous bone formation. Co-culture of chondrocytes with a mesenchymal
      stem cell line was carried out to examine if chondrocytes themselves produced
      paracrine factors that promote osteogenic differentiation. These experiments
      demonstrated that chondrocytes do indeed produce factors that promoted osteogenic
      differentiation. In summary, the results presented here suggest that TNF-alpha
      plays a crucial role in promoting postnatal bone repair through the induction of
      osteoprogenitor cell recruitment or osteogenic cell activation in the context of
      intramembranous bone formation. These results further suggest that the signals
      that promote osteogenesis during endochondral bone formation are different from
      those involved in intramembranous bone formation.

PMID- 11455126
TI  - Morphogenesis of the medial region of the developing mandible is regulated by
      multiple signaling pathways.
AB  - Experimental evidence indicates that the mandibular primordia are specified as at
      least two independent functional regions: two large lateral (proximal) regions
      where morphogenesis is dependent on FGF-8 signaling, and a small medial region
      where morphogenesis is independent of FGF-8 and dependent on other signals. The
      patterns of expression of multiple signaling molecules and regulatory genes in
      the epithelium and mesenchyme of the medial region suggest that the regulatory
      hierarchies controlling morphogenesis of the medial region of the developing
      mandible are complex and involve multiple pathways. Recent genetic studies
      indicate that the 'ET-1-dHAND-Msx1 pathway' constitutes one of the genetic
      pathways involved in outgrowth and morphogenesis of the medial region. Functional
      studies in chick mandible suggest that FGFs (other then FGF-8) and BMPs are also
      part of signaling pathways that regulate morphogenesis of the medial region.
      These studies suggest that in the medial region of the developing mandible, FGF
      mediated signaling is involved in growth-promoting interaction, whereas BMP
      mediated signaling is involved in chondrogenesis.

PMID- 11455127
TI  - Engineered cartilage, bone, joints, and menisci. Potential for temporomandibular
      joint reconstruction.
AB  - Reconstruction of many musculoskeletal structures can be accomplished by bone
      grafting and implantation of prostheses. Alternate approaches are needed,
      however, for repair of complex structures such as articular cartilage surfaces
      and the temporomandibular meniscus and joint. Tissue engineering, either cell
      free or cell-based, offers promise because of recent advances in materials
      research and in our knowledge of the cellular and molecular mechanisms of tissue
      repair. There are three considerations in designing a construct for engineered
      tissue: the source of cells, if any; the nature of the carrier or scaffold; and
      use, if any, of genes, factors, or adjuvants. Autogenous cells, often expanded in
      vitro, have been useful for cartilage tissue engineering. Precursor/progenitor
      cells are advantageous for bone tissue. There are many natural and synthetic
      resorbable materials with good biocompatibility and tissue compatibility that can
      be modified to have the porosity and mechanical properties needed for specific
      applications. The scaffolds can also be modified to provide biological signals to
      augment repair and integration.

PMID- 11455128
TI  - Image-based biomimetic approach to reconstruction of the temporomandibular joint.
AB  - This article will present an image-based approach to the designing and
      manufacturing of biomimetic tissue engineered temporomandibular (TMJ) condylar
      prosthesis. Our vision of a tissue-engineered TMJ prosthesis utilizes a 3-D
      designed and manufactured biodegradable scaffold shaped similar to a condylar
      head and neck, i.e. a condylar-ramus unit (CRU). The fabricated CRU scaffold can
      be constructed with a specific intra-architectural design such that it will
      enhance the formation of tissue from implanted cells placed within its
      interstices. These biologic cues could influence scaffold-implanted mesenchymal
      stem cells (MSC) or bone marrow stromal cells (BMSC) to form a fibrocartilaginous
      joint surface, or cap, on top of a bony strut, similar to a costochondral rib
      graft (CCRG), which could be fixed to the mandibular ramus. This new approach to
      tissue engineering a TMJ would be advantageous because of its patient site
      specific anatomical configuration as well as its potential ability to adapt to
      the loading forces placed on it during function.

PMID- 11455129
TI  - Association analysis of the partially duplicated alpha7 nicotinic acetylcholine
      receptor genetic variant and Alzheimer's disease.
AB  - Changes in the nicotinic acetylcholine receptors (nAChRs) have been demonstrated
      for Alzheimer's disease (AD). Of these receptors, the alpha7 nAChRs, which are
      abundant on hippocampal interneurons, have been implicated in the cytotoxic role
      of the beta-amyloid. Increased mRNA levels of alpha7 nAChR in the peripheral
      lymphocytes and hippocampus of AD patients have been reported. We tested the
      hypothesis that the allelic variant, 2bp deletion, of the partially duplicated
      alpha7 nAChR gene confers susceptibility to Alzheimer's disease. The -2bp
      polymorphism was examined in 120 patients with AD and 98 normal controls. The
      distribution of the partially duplicated alpha7 nAChR genotypes (p = 0.372) and
      alleles (p = 0.465) did not differ significantly for AD patients and controls.
      This negative finding suggests that the partially duplicated alpha7 nAChR genetic
      polymorphism contributes no major effect to the development of AD. However, we
      suggest that the other genetic variation of the alpha7 nAChR gene, related to AD
      or the associated symptomatology, merits further investigation.

PMID- 11455130
TI  - Analysis of alpha-2-macroglobulin-2 allele as a risk factor in Alzheimer's
      disease.
AB  - A correlation between a 5-nucleotide deletion polymorphism in the A2M gene and an
      enhanced risk of developing Alzheimer's disease (AD) was reported. We studied
      this polymorphism in sporadic AD patients and patients with frontotemporal
      dementia (FTD) by using an electrophoretical separation of PCR products on a
      Metaphor gel. Our results did not show any significant difference between A2M-2
      allelic frequency (p = 0.89) or genotype frequency (p = 0.97) in the two
      different clinical series and in control subjects. The frequencies were not
      significantly different after stratification by APOE epsilon4 status.

PMID- 11455131
TI  - Homocysteine and cognitive decline in healthy elderly.
AB  - Serum homocysteine is increased, and correlates inversely with cognitive scores,
      in Alzheimer's disease (AD), vascular dementia and "age-associated memory
      impairment". Elevated levels might signal accelerated cognitive decline, although
      this remains to be established. We therefore repeated Mini-Mental State
      Examinations, together with additional ADAS-Cog assessments, in 32 healthy
      elderly individuals to determine whether prior homocysteine levels predicted
      cognitive changes over a 5-year period. Homocysteine predicted follow-up
      cognitive scores and rate of decline in cognitive performance independently of
      age, sex, education, renal function, vitamin B status, smoking and hypertension
      (p < 0.001). Homocysteine predicted word recall (p = 0.01), orientation (p =
      0.02) and constructional praxis scores (p < 0.0001). One subject, with the second
      highest initial homocysteine, had developed probable AD at follow-up. Fasting
      total serum homocysteine appears to be an independent predictor of cognitive
      decline in healthy elderly and exerts a maximal effect on spatial copying skills.

PMID- 11455132
TI  - Decreased levels of intrathecal interleukin 1 receptor antagonist in Alzheimer's
      disease.
AB  - A growing body of evidence points out the potential role of inflammatory
      mechanisms in the pathophysiology of brain damage in dementia. In previous
      studies, we have demonstrated intrathecal production of the proinflammatory
      cytokine tumor necrosis factor (TNF)alpha in patients with Alzheimer's disease
      (AD). The aim of the present study was to investigate the downstream products of
      TNF-alpha expression including interleukin (IL)1beta and its naturally occurring
      antagonist IL-1 receptor agonist (ra) in patients with AD. The cytokine levels
      were related to neuronal damage, as measured by intrathecal tau and beta-amyloid
      concentration and certain clinical features of the disease. Fifty-two patients
      with AD and 25 healthy controls were analyzed with respect to cerebrospinal fluid
      (CSF) levels of IL-1beta and IL-1ra. CSF IL-1beta was neither detectable in CSF
      of AD nor in control CSF. In contrast, a significantly lower (p < 0.01) number of
      patients (24 of 49) than of controls (20 of 24) showed detectable levels of IL
      1ra in the CSF. The intrathecal levels of IL-1ra were significantly lower in
      patients with AD than in the controls. Our study demonstrates a decreased
      production of the anti-inflammatory compound IL-1ra, suggesting a propensity
      towards inflammation in patients with AD.

PMID- 11455133
TI  - Relationship between blood flow kinetics and severity of Alzheimer's disease:
      assessment of severity using a questionnaire-type examination, Alzheimer's
      disease assessment scale, cognitive sub-scale (ADAS(cog)).
AB  - We assessed hemokinetics associated with changes in Alzheimer's disease (AD)
      severity in 90 AD patients by researching the relationship between AD Assessment
      Scale, cognitive sub-scale (ADAS(cog)) scores and regional cerebral blood flow
      (rCBF). In the present study, we employed the questionnaire-type ADAS(cog)
      examination to accurately assess the severity of AD. Between five groups
      classified on the basis of ADAS(cog) score, significant differences were observed
      in parietal, lateral temporal and superior frontal rCBF. In addition, in parietal
      and lateral temporal regions, significant correlations were also observed between
      ADAS(cog) score and rCBF. In superior frontal rCBF, significant differences were
      noted only between group 5 (> or =40 ADAS(cog) points) and each of the other
      groups; there was no significant correlation between rCBF and ADAS(cog) score.
      Thus, we propose the following mechanism for blood flow kinetics associated with
      changed severity: In an early stage of AD, blood flow in the medial temporal
      cortex is impaired, and gradually involves the temporoparietal regions. While the
      medial temporal impairment of blood flow reaches a plateau, temporoparietal blood
      flow continues to be impaired well into a severe stage, at which point blood flow
      impairment in the frontal region is initiated.

PMID- 11455134
TI  - Unidimensional scale for dementia.
AB  - A cognitive test comprising 27 subscales was administered to 262 demented
      patients and 92 normal subjects. Principal factor analysis followed by varimax
      and Harris-Kaiser rotation and Guttman's scalogram analysis was performed. The
      analysis yielded three factors, i.e. "recent memory", "immediate memory or
      attention" and "remote memory". The relationships between the three-dimensional
      distribution of the scores and the DSM-IIIR grade of dementia indicated the
      existence of a continuum of dementia severity. Scalogram analysis showed
      unidimensionality in the difficulty level of the subscales as well as in the
      severity of the cases. Thus, the simple summary score can be used as a good
      measure of the severity of dementia.

PMID- 11455135
TI  - Innovative dementia care: functional status over time of persons with Alzheimer
      disease in a residential care centre compared to special care units.
AB  - Residential care centres (RCCs) for persons with Alzheimer disease are increasing
      worldwide, but there are few studies that compare the functional outcomes of RCC
      residents to residents of other types of continuing care settings. This study
      compared residents of the first Canadian RCC on physical, cognitive, behavioural
      and emotional functioning 6, 12 and 18 months after admission to residents of
      special care units (SCUs) operated by the same continuing care provider. SCU
      residents were initially functioning lower than RCC residents on most outcome
      measures and these differences persisted over time. Resident functioning declined
      over time regardless of care setting and, when the initial status was controlled
      for, the rates of decline were similar. However, RCC residents experienced
      greater independence/freedom of choice, fewer physical or psychotropic medication
      restraints and were more active, which may have enhanced their quality of life.

PMID- 11455136
TI  - The Bayer-Activities of Daily Living Scale (B-ADL): results from a validation
      study in three European countries.
AB  - The Bayer-Activities of Daily Living Scale (B-ADL) is a 25-item, informant-rated
      questionnaire which was developed as a brief and internationally applicable
      instrument for assessing functional disabilities. The scale's target group are
      elderly patients suffering from mild to moderate dementia or cognitive
      impairment. To investigate the reliability and validity of different language
      versions, the B-ADL was administered in the UK, Germany, and Spain to a total of
      1,433 subjects with a wide range of cognitive decline. The results from the three
      country samples were very similar, with internal consistency being above 0.98
      (Cronbach alpha). A factor analysis revealed that a one-factor solution accounted
      for most of the variance. The B-ADL total score significantly increased between
      adjacent Global Deterioration Scale (GDS) stages 1 to 5. A second factor analysis
      entering additional variables (GDS stage, Mini-Mental State Examination or MMSE
      subscores, age, years of education, gender, and country) revealed that all B-ADL
      items loaded on the same factor, "dementia severity", and that they were not
      related to age, education, gender, or country. In the identification of subjects
      with clinically manifest dementia symptoms (GDS stages 4 and 5), the B-ADL proved
      to be as efficient as the MMSE in the UK and German samples and superior to the
      MMSE in the Spanish sample.

PMID- 11455137
TI  - The value of hair cosmetics and pharmaceuticals.
AB  - As early as can be traced, written documents testify endeavors shown by humanity
      to please by means of the hair. Hair care, color and style play an important role
      in people's physical appearance and self-perception. Dermatologists should be
      knowledgeable about the procedures people follow to look their best and should
      have the competence to provide patients with information on the benefits and
      hazards of hair cosmetics and pharmaceuticals. Shampooing is the most common form
      of cosmetic hair treatment. The diversity of qualities expected from a shampoo by
      today's consumer surpass the primary function of cleansing. Current shampoo
      formulations are adapted to the variations associated with hair quality, hair
      care habit and specific problems related to the superficial condition of the
      scalp. Hand in hand, test methods are developed to evaluate the efficacy of hair
      care products so that consumers are offered products that perform as claimed.
      Through the development of cosmetics with pharmaceutically active compounds,
      products are evolving that are becoming more similar to topical therapeutic
      agents (cosmeceuticals). The efficacy of cosmeceuticals that claim to act as hair
      growth stimulants should be measured by the standards set by the drugs minoxidil
      and, more recently, oral finasteride. Finally, health hazards associated with the
      use of hair care products, especially rinse-off products, have been
      overemphasized by the media and need careful correction by opinion leaders.

PMID- 11455138
TI  - Usefulness of histological examination for the diagnosis of onychomycosis.
AB  - BACKGROUND: [corrected] Direct microscopy and culture tests currently used in the
      diagnosis of nail mycosis can yield false-negative results, and confirmation of
      the pathogenic agent, especially in non-dermatophyte infections, is often a
      lengthy process. OBJECTIVE: The aim of this study was to investigate the
      usefulness of the histological examination of nail clipping samples in
      supplementing the standard microscopic and culture techniques for the diagnosis
      of onychomycosis. PATIENTS AND METHODS: One hundred and seventy-two subjects
      affected by nail alterations suggestive of onychomycosis were evaluated. Nail
      specimens were studied with 3 different techniques: direct microscopic
      examination of a 40% KOH clarified preparation, fungal culture and histological
      examination. Patients positive for fungal infection were re-evaluated with the
      same techniques after treatment with oral terbinafine, fluconazole or
      itraconazole and topical application of bifonazole or ciclopirox for 2 months.
      RESULTS: Direct microscopy was positive in 102 (59.3%) nail specimens. The
      culture test was positive in 90 cases (52.9%), showing a dermatophyte in 45, a
      yeast in 23 and a mould in 22 samples. The histological examination was positive
      in 94 (54.6%) samples. In 4 cases, it was the only investigation confirming the
      clinical diagnosis of nail mycosis. In most of the cases, the morphological
      aspect of the hyphae and/or spores suggested also to which group of pathogens
      (dermatophytes, yeasts or moulds) the mycetes observed in the histological
      sections could be ascribed. The concurrent presence of a dermatophyte and a mould
      was evidenced in a few specimens. The control histological examination at the end
      of the treatment showed negative results or residual non-vital hyphae and/or
      spores. CONCLUSIONS: Results of the present study indicate that the histological
      examination of nail clipping specimens is a relatively inexpensive, rapid and
      easily performed procedure. It is useful to confirm or refute the results of
      routine microscopy and culture tests. Moreover, nail histopathological
      observation may help in ascribing a pathogenic role of non-dermatophyte isolates
      and evaluating the effectiveness of antifungal treatment.

PMID- 11455139
TI  - Solar damage in skin tumors: quantification of elastotic material.
AB  - BACKGROUND: The elastotic changes of the dermis are thought to be the primary
      indicator of the cumulative sun exposure of the dermis. The changes of elastotic
      material have been evaluated by several previous methods, but these did not
      quantitatively measure the amount of elastic tissue. OBJECTIVE: The purpose of
      this study was to quantify dermal elastosis and to assess the significance of sun
      exposure in the pathogenesis of nonmelanomatous skin tumors such as basal cell
      carcinoma (BCC), squamous cell carcinoma (SCC) and Bowen's disease (BD). METHODS:
      Ninety-nine sections from biopsy specimens of histopathologically proven BCC, SCC
      and BD were stained with Verhoeff-van Gieson stains. We studied the amount of
      elastotic material adjacent to the tumor by image analysis. RESULTS: There was a
      3- to 4-fold increase in the amount of elastotic material in BCC and SCC compared
      to the sun-exposed skin of normal controls (p < 0.0001). The amount of elastotic
      material was increased 1.3 times in BD as compared with the nonexposed skins of
      normal controls (p < 0.01). CONCLUSION: We demonstrated a quantitative
      relationship between cumulative solar exposure and skin cancer such as SCC, BCC
      and BD.

PMID- 11455140
TI  - Dual diagnosis of Pemphigus and pemphigoid. Retrospective review of thirty cases
      in the literature.
AB  - BACKGROUND: Pemphigus and pemphigoid are two distinct groups of autoimmune
      blistering diseases. There are many reports of the simultaneous presence of
      clinical and serological features of both diseases in the same patient.
      OBJECTIVE: This study is a retrospective review of the present literature on
      reports of patients with features of both pemphigus and pemphigoid. We recommend
      that these patients be considered as having a dual diagnosis. METHODS: A review
      of the English language, peer-reviewed literature was conducted on patients
      described with features of pemphigus and pemphigoid. Available data on clinical
      profile, histology, immunopathology, treatment, follow-up and outcome were
      studied in 30 patients. They were divided into three groups: (1) bullous
      pemphigoid and pemphigus vulgaris, (2) mucous membrane or cicatricial pemphigoid
      and pemphigus vulgaris and (3) bullous pemphigoid and pemphigus foliaceus.
      RESULTS: In all three groups, most patients had a clinical phenotype resembling
      both diseases. In 17 patients with bullous pemphigoid and pemphigus vulgaris, 83%
      had a skin biopsy consistent with bullous pemphigoid, 70% had direct
      immunofluorescence studies typical of bullous pemphigoid and sera of 83% had
      antibodies typical of pemphigus vulgaris on indirect immunofluorescence. In 10
      patients with mucous membrane or cicatricial pemphigoid and pemphigus vulgaris, a
      histology of mucous membrane pemphigoid was reported in 60% of the patients,
      direct immunofluorescence studies typical of mucous membrane pemphigoid were
      reported in 70% of the patients and in 80%, autoantibodies characteristic of
      pemphigus vulgaris were observed. In 3 patients with bullous pemphigoid and
      pemphigus foliaceus, the histologies were consistent with bullous pemphigoid,
      direct immunofluorescence was typical of pemphigus foliaceus and their sera had
      both autoantibodies. The majority of the 30 patients required long-term high-dose
      corticosteroids and immunosuppressive agents to control their disease. Three
      patients with bullous pemphigoid and pemphigus vulgaris (18%) died due to effects
      of prolonged immunosuppression. CONCLUSION: We characterize a group of patients
      who have clinical, histological and immunopathological features of bullous or
      mucous membrane or cicatricial pemphigoid with serological features of pemphigus.
      These patients did not achieve a prolonged clinical remission by conventional
      therapy. It is possible that early identification of these patients may improve
      their prognosis.

PMID- 11455141
TI  - Acute herpes zoster neuralgia: retrospective analysis of clinical aspects and
      therapeutic responsiveness.
AB  - BACKGROUND: Although the efficacy of modern antiviral agents for the treatment of
      herpes zoster is unquestioned, their ability to affect the associated pain
      remains controversial. OBJECTIVE: We have therefore evaluated the inpatient
      hospital records of 550 patients with herpes zoster with regard to pain-related
      clinical aspects and therapeutic responsiveness. METHODS: Intensity of pain was
      quantified by calculating a daily pain equivalence index (PEI) on the basis of
      different classes of pain medication and the number of tablets used in each
      category. RESULTS: The mean age of patients was 66.7 years, cranial segments were
      predominantly involved (55%), 64% of patients suffered from associated diseases
      and 77% experienced herpes-related pain. The PEI was 0.90 in the entire patient
      population, with significantly higher values in women and in patients with 3 or
      more associated diseases. It was lower in sacral and cranial nerve involvement,
      and it decreased rapidly in patients prior to discharge from hospital. Although
      there were significant differences in hospital stay between patients who received
      aciclovir and those who did not (mean 20.3 vs. 23.8 days), and for high- versus
      low-dose oral or intravenous administration, no significant differences were
      noted between the two groups for initial PEI values and during the course of
      observation, irrespective of the route of administration or the dose of aciclovir
      and the individual patient's PEI value. The groups were otherwise closely similar
      with regard to basic demographic and clinical data. 23.3% predominantly aged
      female patients with more associated diseases than the total patient population
      had a persistently elevated PEI and stayed in hospital beyond 21 days (mean 35.1
      days), representing patients who went on to postherpetic neuralgia. CONCLUSION:
      These data further delineate clinical aspects of acute herpes zoster neuralgia,
      underline the unsolved therapeutic problems associated with this condition
      despite otherwise effective antiviral treatment, and characterise a subgroup of
      patients at risk to develop postherpetic neuralgia.

PMID- 11455142
TI  - Assessment of the water content of the stratum corneum using a sorption
      desorption test.
AB  - BACKGROUND/AIM: Various instruments based on electrical properties of the skin
      are currently used to assess the stratum corneum (SC) hydration state or water
      holding capacity. However, no direct relation with the quantity of water measured
      is provided. The objective of the present study was to calibrate the Corneometer,
      a device displaying electrical-capacitance-related values (which reflect the skin
      hydration state), and the amount and behaviour of the water taken up by the outer
      part of the SC during a sorption-desorption test. METHODS: The experiment was
      performed on the ventral forearms of 20 healthy volunteers after a rest in an
      environmentally controlled room. Corneometer and transepidermal water loss (TEWL)
      values were measured at intervals over the desorption process. The areas under
      the TEWL-versus-time curve provided the absolute amounts of residual sorbed
      water. RESULTS: The decrease kinetics of both signals after subtraction of
      prehydration values were very similar and bi-exponential, both showing a rapid,
      then a slower phase. The absolute amount of water taken up by the SC
      (hygroscopicity) and the two desorption rates were obtained. The Corneometer
      values were mono-exponentially related to the amount of water remaining within
      the SC. This allowed the in vivo calibration of the Corneometer in terms of
      absolute amount of water over the desorption range. CONCLUSION: The method may be
      used to calibrate in vivo other electrical devices aimed at assessing SC
      hydration during a sorption-desorption test. It may also provide new ways to
      measure SC water uptake and water holding capacity following application of
      products.

PMID- 11455143
TI  - Combination therapy improves the recovery of the skin barrier function: an
      experimental model using a contact allergy patch test combined with TEWL
      measurements.
AB  - BACKGROUND: Nickel (Ni) allergic contact dermatitis (ACD) alters the skin
      barrier. OBJECTIVE: Our aim was to compare the efficacy of combination therapies
      on ACD, using a topical corticosteroid and a corneotherapy agent (barrier cream),
      with that of a single therapy with corticosteroids. METHODS: On day 1, 3 Ni test
      patches were applied on each forearm of 14 Ni-patch-test-positive females. Four
      contained 5% Ni and 2 physiological saline. Either topical corticosteroid or
      barrier cream were matched with the combination of both products on 3 of the 4 Ni
      ACD. The fourth was not treated. Clinical scoring, transepidermal water loss
      (TEWL) and stratum corneum (SC) capacitance were measured before (day 1) and
      after (days 4-8) ACD. RESULTS: The combination therapy showed a significant
      decrease in TEWL values and an increase in SC capacitance. CONCLUSION: Combining
      a topical corticosteroid with corneotherapy agents prevents the delay in the
      healing process of skin barrier disruption due to ACD.

PMID- 11455144
TI  - Epidermal grafting for depigmentation due to discoid lupus erythematosus.
AB  - BACKGROUND: Longstanding lesions of discoid lupus erythematosus (DLE) may heal
      with thin, depigmented scar(s). The depigmentation may fail to respond to medical
      therapies. OBJECTIVE: To evaluate the efficacy of suction blister epidermal
      grafting in longstanding, quiescent, depigmented scar(s) of DLE. METHODS: The
      suction blisters were raised on the lateral aspect of the upper third of the
      thigh in 4 patients (3 males, 1 female) with depigmented scars of DLE on the
      face. The roofs of the blisters were transferred to the dermabraded recipient
      area. Both donor and recipient sites were dressed with nonadherent tulle.
      RESULTS: The dressings were removed after 7 days. The graft take was complete.
      The pigmentation achieved was more than 100% of the grafted area due to
      peripheral spread of the pigmentation and more than 75% of the depigmented area.
      The color match was good. There was no loss of pigment or recurrence/relapse of
      the disease during the follow-up of 6 months to 1 year. CONCLUSIONS: Our
      preliminary results suggest that leukodermic scars of healed inactive DLE lesions
      can be successfully treated with epidermal grafting.

PMID- 11455145
TI  - Unusual halo nevi--darkening rather than lightening of the central nevus.
AB  - Although the classic halo nevus is a brown nevus with a surrounding rim of
      depigmentation, i.e. a stage I halo nevus, these nevi can have several clinical
      stages. The central nevus may lose its pigmentation and appear pink with a
      surrounding halo (stage II), the central papule may disappear leading to a
      circular area of depigmentation (stage III) or the depigmented area may repigment
      (stage IV), leaving no trace of its prior existence. Herein we describe an
      unusual phenomenon--darkening of the central nevus rather than lightening-
      following the appearance of the halo phenomenon. An 18-year-old boy who had
      multiple atypical nevi developed multiple halo nevi beginning at the age of 12
      years. Following the appearance of the peripheral halos, 2 of his nevi that were
      originally solid medium brown in color darkened and the hyperpigmentation had a
      reticulated pattern with perifollicular sparing. One possible explanation is a
      postinflammatory hyperpigmentation induced by the infiltrating lymphocytes.

PMID- 11455146
TI  - Swelling of the proximal nail fold caused by underlying warts.
AB  - We report on 2 cases of patients with warts underlying the proximal nail fold
      which presented as tender erythematous nodules. The remarkable feature in both
      cases was a significant oedema of the proximal nail fold, resembling a reaction
      to a foreign body. One patient responded well to mild keratolytic treatment. The
      second patient was treated surgically with crescentic excision of the distal
      portion of the proximal nail fold. It is important to recognise this tumour
      variant in order to avoid unnecessary or excessive intervention.

PMID- 11455147
TI  - Asthma, rhinitis and dermatitis triggered by fungal infection: therapeutic
      effects of terbinafine.
AB  - We report 2 atopic patients suffering from tinea unguium caused by Trichophyton
      rubrum. In addition, both patients had symptoms of allergies: one had perennial
      rhinoconjunctivitis and bronchial asthma, the other had chronic dermatitis of the
      face and neck. In both cases, their allergy symptoms improved dramatically during
      oral therapy with the antifungal agent terbinafine (250 mg/day) and relapsed
      after its discontinuation.

PMID- 11455148
TI  - Persistent plaques and linear pigmentation in adult-onset Still's disease.
AB  - A 25-year-old Japanese man presented with high spiking fever, arthralgia and a
      skin rash. A pruritic edematous erythema with persistent plaques was found mainly
      on the trunk; these lesions persisted even when the fever subsided, with
      prominent linear pigmentation. As marked neutrophilia and a high level of serum
      ferritin were detected, a diagnosis of adult-onset Still's disease (AOSD) was
      made, even though the persistent eruption was not characteristic of the disease.
      Oral prednisolone, together with low-dose methotrexate, was given with good
      results. In the literature, a similar atypical rash has been reported in 11 cases
      in Japan. All of them required high-dose administration of corticosteroids or
      other immunosuppressive agents. Severe systemic complications were seen in 3
      patients, and 2 cases died of the disease. Persistent plaques and linear
      pigmentation are some of the manifestations of AOSD, which cannot be overlooked.
      This appearance could be an indication that suggests an increased risk of
      systemic complications and a prolonged time to clinical remission.

PMID- 11455149
TI  - Zosteriform metastatic skin cancer: report of three cases and review of the
      literature.
AB  - BACKGROUND: Metastatic skin cancer is a rare complication of internal
      malignancies. Patients who do develop skin metastases seldom present with a
      zosteriform distribution. OBJECTIVE: To elucidate the characteristics of
      zosteriform metastatic skin cancer, 15 cases from the medical literature and 3
      cases seen in our clinic were reviewed clinically and histopathologically.
      METHODS: The age and sex of each patient, site of the primary tumor, pathology of
      primary and metastatic lesions, location of the skin cancer and presence of pain
      were determined for the 18 cases of zosteriform skin cancer. RESULTS: The most
      frequent site of the primary tumor was the breast (4 cases), ovary or lung (3
      cases each), prostate, bladder or stomach (2 cases each) and uterus or colon (1
      case each). The most common site of the skin metastases was the chest wall (8
      cases) and abdominal wall (7 cases). The histology of the primary lesion was
      compatible with adenocarcinoma (10 cases), transitional cell carcinoma or serous
      papillary cystadenocarcinoma (2 cases each) and ductal carcinoma (1 case). Eleven
      cases developed on the nearest covering skin and/or on the same side as the
      primary tumor. Eleven patients complained of pain. Seven cases were treated as
      herpes zoster with antiviral agents. CONCLUSION: Approximately 50% of cases of
      metastatic skin cancer developed on the nearest skin covering and on the same
      side as the primary tumor. This evidence may be useful when trying to pinpoint
      the location of the primary tumor. One third of patients with skin metastases
      were misdiagnosed and their lesions were treated initially as herpes zoster. When
      a band-like eruption is seen in patients with internal malignancies, the
      possibility of metastatic skin lesions should be considered. A skin biopsy is
      necessary to confirm the diagnosis.

PMID- 11455150
TI  - UV light does not induce p53 mutation in melanocytes in vitro.

PMID- 11455151
TI  - Unilateral multiple linear lichen planus following the Blaschko lines recurring
      after deliveries.

PMID- 11455152
TI  - Severe childhood pemphigus vulgaris aggravated by enalapril.

PMID- 11455153
TI  - Mycophenolate mofetil for dermatomyositis.

PMID- 11455154
TI  - Angiolymphoid hyperplasia with eosinophilia: successful treatment with interferon
      alpha 2b.

PMID- 11455155
TI  - Morsicatio linguarum as a lapsus linguae: a linguistic poem.

PMID- 11455156
TI  - Hypertriglyceridaemia during low-dose interferon alpha-2b treatment in a patient
      with Kaposi's sarcoma.

PMID- 11455157
TI  - Wegener's granulomatosis: description of a case where cutaneous involvement was
      correlated with elevation of the c-ANCA titer.
AB  - Wegener's granulomatosis is a systemic disease characterized by necrotizing
      granulomas and vasculitis involving the upper and lower respiratory tract as well
      as the kidneys. Cutaneous manifestations consist mainly of papules or
      papulonecrotic lesions. c-ANCA are known to be a valuable adjunct for the
      diagnosis and follow-up of Wegener's granulomatosis with systemic involvement. We
      report the case of a 49-year-old man with Wegener's granulomatosis who developed
      two relapses of the disease with cutaneous manifestation and who presented with
      concomitant elevation of the c-ANCA and more precisely the subset PR3-ANCA during
      the acute phase of the disease.

PMID- 11455158
TI  - Bazex syndrome.
AB  - Bazex syndrome is a paraneoplastic acrokeratosis appearing mostly at the same
      time as the underlying neoplasm. We report a typical case with a squamous cell
      carcinoma of the tongue and classical cutaneous symptoms disappearing with the
      treatment of the tumour.

PMID- 11455159
TI  - Bilateral carpal tunnel syndrome as a clue for the diagnosis of systemic
      amyloidosis.
AB  - A 60-year-old Swiss woman presented with a 1-year history of periorbital
      hemorrhagic papules, a tendency to develop hematoma due to minor trauma and
      shortness of breath. The personal medical history included surgery for bilateral
      carpal tunnel syndrome (CTS) 2 years ago. Clinical and laboratory findings
      included macroglossia, Bence-Jones proteinuria, reticular lung infiltrates,
      thickening of the ventricular walls in echocardiography and increase in atypical
      plasma cells in the bone marrow. The coexistence of the specific symptoms of CTS,
      macroglossia and cutaneous lesions should immediately alert the physician to the
      probable existence of plasma-cell-dyscrasia-related systemic amyloidosis.

PMID- 11455160
TI  - Cold agglutinin disease--the importance of cutaneous signs.
AB  - We present the case of a woman where the diagnosis of cold agglutinin disease
      could be made after we had noticed slight cutaneous manifestations during a
      routine examination. Leading symptoms were livedo reticularis of the thighs and a
      history of acrocyanosis and Raynaud's phenomenon upon cold exposure. The current
      knowledge about the etiology, clinical presentation and treatment of the disease
      is briefly discussed.

PMID- 11455161
TI  - Skin cancers in organ transplant recipients: two cases of virus-induced
      neoplasms.
AB  - Immunosuppression profoundly influences the prevalence of skin disorders in
      transplant recipients. Skin tumors occur with high incidence and constitute a
      major part of transplantation-related morbidity and mortality. We report on 2
      immunosuppressed patients presenting with rapidly growing epithelial and
      mesenchymal neoplasms after renal transplantation. The diagnostic approach,
      differential diagnosis and treatment options are discussed emphasizing the
      characteristics of cutaneous lesions in immunosuppressed transplant recipients.

PMID- 11455162
TI  - Cowden syndrome-diagnostic skin signs.
AB  - Cowden syndrome is a rare autosomal dominant familial cancer syndrome with a high
      risk of breast cancer. The most important clinical features include carcinomas of
      the breast and thyroid, and hamartomatous polyps of the gastrointestinal tract.
      There are characteristic mucocutaneous features which allow early recognition of
      the disease and are generally present before internal malignancies develop. We
      report on a woman in whom the diagnosis of Cowden syndrome was first made after
      she had been treated for both breast cancer and melanoma.

PMID- 11455163
TI  - Ulcerative sarcoidosis successfully treated with apligraf.
AB  - The case of a 73-year-old female patient is reported with a 25-year-long history
      of widespread cutaneous sarcoidosis without any known extracutaneous
      manifestations. The skin manifestations started with erythematous and plaque-like
      lesions that had ulcerated on the legs for the last half-year. A relevant venous
      insufficiency or other etiology of the ulcers could not be found. Histology from
      lesions of the trunk and from the surroundings of the ulcers revealed the typical
      noncaseating granulomas. A systemic involvement could not be observed; leukopenia
      and a slightly elevated angiotensin-converting enzyme level in the serum were
      found. Topical steroids did not prove successful on the ulcers. Apligraf, a
      bilayered skin equivalent, was transplanted twice on the ulcers leading to
      complete closure within 3 months. A therapy with systemic steroids could thus be
      avoided.

PMID- 11455164
TI  - Vulvodynia after CO2 laser treatment of the female genital mucosa.
AB  - We have observed 3 cases of vulvodynia after CO2 laser (pulse or scan) treatment
      of condylomata acuminata (n = 1) or bowenoid papulosis (n = 2) of the female
      genital mucosa. Laser treatment was associated with a considerable delay in
      healing (3-4 months) and chronic pain. The histology of the treated areas showed
      a scar tissue and severe mucosal atrophy. The occurrence of painful scars
      following CO2 laser treatment could be related to an inadequate laser technique
      considering the morphology of the vagina.

PMID- 11455165
TI  - Chronic borreliosis presenting with morphea- and lichen sclerosus et atrophicus
      like cutaneous lesions. a case report.
AB  - We report on a case of chronic cutaneous borreliosis with manifestations
      clinically compatible with morphea and lichen sclerosus et atrophicus. The
      histopathologic features of these lesions were those of acrodermatitis chronica
      atrophicans. Our case illustrates the concept that clinical aspects of morphea
      and lichen sclerosus et atrophicus pertain to the spectrum of cutaneous
      borreliosis.

PMID- 11455166
TI  - Alopecia syphilitica: report of two cases in Geneva.
AB  - Two patients with alopecia syphilitica are presented. Moth-eaten alopecia is the
      most typical look of secondary syphilis on the scalp. With the decrease in
      syphilis cases in western countries, this rarer clinical manifestation tends to
      be misdiagnosed.

PMID- 11455169
TI  - Involuntary treatment of alcohol-dependent patients: a study of 17 consecutive
      cases of civil commitment.
AB  - AIM: To investigate the baseline and follow-up characteristics of a group of
      alcohol-dependent patients being treated under civil commitment. METHODS: This
      study involved a cross-sectional comparative analysis of baseline characteristics
      and a follow-up survey of a group of committed alcoholic patients. The study was
      undertaken in the Alcohol Unit of a 1,000-bed general and university hospital.
      The study included 17 consecutive cases of civil commitment (representing 15
      patients, of whom 2 were committed twice) and a comparative group of 34 randomly
      selected age- and sex-matched patients. Baseline characteristics of the cases (at
      the time of commitment) and of patients from the comparative group were collected
      from medical records, including sociodemographic data, medical condition,
      patterns of drinking and number and dates of previous treatments for alcohol
      related problems. A structured follow-up interview of the cases provided
      information on their medical condition, social status, patterns of alcohol use,
      type and duration of residential treatment as well as their perceptions of
      commitment. RESULTS: During a 4-year period, our Unit referred 23 cases of
      alcohol-dependent patients (out of 367) to the Guardianship Authority, requesting
      civil commitment. On 17 occasions, patients were committed to residential
      treatment, including 2 patients who underwent commitment on two separate
      occasions, thus representing a total of 15 different patients. In comparison with
      age- and sex-matched patients seen at the Unit, the cases were characterized by
      multiple medical, social and psychological alcohol-related impairments. At the
      time of follow-up, 14 out of 15 patients were alive, among whom 10 agreed to be
      interviewed. Eight of these reported complete abstinence, whereas 9 considered
      their alcohol problem as less severe than before. The average duration of
      commitment was 29 weeks. The majority of patients retrospectively considered the
      measure as having been justified and useful. The patients' satisfaction with the
      decision to commit was higher among women than among men. Health-related quality
      of life at the time of follow-up, as assessed by the MOS 36-Item Short Form
      Health Survey questionnaire, was good on average and better than that usually
      reported by other cohorts of alcoholics undergoing treatment. CONCLUSIONS: The
      usefulness of residential civil commitment of certain severely impaired alcohol
      dependent patients is underscored. This study suggests that civil commitment not
      only may save the lives of endangered patients but could also be a health
      promoting measure that may sometimes allow for recovery from dependence.
      Unexpectedly, this measure was retrospectively well accepted by many patients,
      who considered the commitment decision as having been justified and useful.

PMID- 11455170
TI  - Replacing the last week of a motivational inpatient alcohol withdrawal programme
      by a day-clinic setting.
AB  - The impact on the motivation to treatment of a qualified alcohol withdrawal
      programme was evaluated in a pre/post setting. Over a period of 2 years we
      compared the results of replacing the last week of an inpatient setting by day
      clinic treatment. In the first year, 202 patients were treated in a 3-week
      inpatient setting, whereas in the second year, 149 patients out of 212 (70.3%)
      changed into day-care for the third week. The total treatment period was nearly
      equal in both years (16.2-17.4 days) and the average costs of detoxication were
      reduced by 8%. The amount of irregular discharges (21.7 vs. 23.6%) was almost
      unchanged. As a severe disadvantage the overall rate of patients who agreed to
      enter a succeeding stringent long-term treatment regressed significantly from
      45.0 to 34.4% (p < 0.05).

PMID- 11455171
TI  - An evaluation of the therapeutic programme conducted by the Southern Regional
      Alcohol-Abuse Treatment Centre: study on the programme's results one year after
      discharge from inpatient care.
AB  - Given the clinical and social problems caused by the consumption of alcohol in
      most industrialised countries, there is a strong need to develop and evaluate the
      effectiveness of integrated care programmes. In this study, the authors describe
      the results observed in 124 sequentially admitted subjects at various points
      throughout the course of the first year after their discharge from the Southern
      Regional Alcohol-Abuse Treatment Centre (CRAS) in Lisbon, Portugal. An inpatient
      stay at this unit of CRAS lasts for between 5 and 7 weeks and implies that the
      patient must submit him/herself to a therapeutic model which has been adapted
      from the Minnesota model. At the end of the year under study 44.3% of the
      patients were still abstinent, 40.3% were consuming alcohol and 15.4% did not
      reply. 51 patients (41.1% of the initial sample) were still in regular contact
      with CRAS for further treatment at that point. The variable that was found to
      possess the most significant association with a favourable outcome was adherence
      to the therapeutic programme over the course of that year.

PMID- 11455172
TI  - Are the Twelve Steps more acceptable to drug users than to drinkers? A comparison
      of experiences of and attitudes to Alcoholics Anonymous (AA) and Narcotics
      Anonymous (NA) among 200 substance misusers attending inpatient detoxification.
AB  - The present study is a cross-sectional interview-based investigation comparing
      experiences of and attitudes towards Alcoholics Anonymous (AA) and Narcotics
      Anonymous (NA) in a sample of 200 patients attending inpatient substance misuse
      detoxification services. Two hundred consecutive admissions were recruited; 100
      each from one drug and one alcohol in-patient treatment service in which
      attendance at AA/NA was a voluntary adjunct to a generic treatment programme.
      Although there were no differences in the history of AA/NA attendance, the drug
      users (who were on average younger) reported significantly more positive
      attitudes towards AA/NA, more willingness to attend during their in-patient
      treatment and greater intention to attend following completion of their
      detoxification. In particular, despite no differences in spiritual/religious
      orientation, the drug users reported more positive views of the Twelve Steps. As
      AA/NA remain popular and accessible forms of substance misuse support, it is
      critical that we develop a clearer understanding of their impact and of the scope
      for their integration with generic forms of substance misuse treatment.

PMID- 11455173
TI  - Understanding heroin as a "rational addiction".
AB  - This paper makes some interpretations on the Becker and Murphy model of rational
      addiction so as to consider policy issues beyond the discussion of the effects of
      price on heroin consumption. Through the model of the rational heroin user, this
      paper argues that heroin use is a symptom of other factors. The focus of the
      analysis is placed on the negative life events that underpin heroin consumption.
      Thus, policy makers who want to stop heroin use may find it more effective to
      first stop the underlying problems that are the cause of the catalytic
      consumption of heroin use. It may prove better to promote other religious, family
      and educational activities than to actively discourage heroin use.

PMID- 11455174
TI  - Sports activities in the prevention of heroin dependency.
AB  - The aim of this study was to find out more about the role played by sports
      activities in the prevention of illicit drug abuse. We administered a simple
      questionnaire to a group of 215 patients with heroin dependency. Their average
      age was 23 years (SD = 4.3, range 15-42); 163 (76%) of them were males and 52
      (24%) females. Another group was formed by 231 student adolescents with a mean
      age of 15 years (SD = 1.0, range 14-18); 65 (28%) were males and 166 (72%) were
      females. One hundred and sixty-one (75%) of the heroin users and 169 (69%) of the
      students took part in regular physical training (at least two times weekly in a
      sport club) and competitive sports activities until the age of 15. Due to the
      fact that there was a statistically significant difference in the male/female
      ratio between the two groups, the comparison of males and females was done
      separately. There were no statistically significant differences between the
      males, nor between the females from these two groups in their histories of sports
      activities until the age of 15. Thirty-one (17%) of the patients started with
      illicit drug use prior to the termination of their sports activities.

PMID- 11455175
TI  - Prevention of suicide by naltrexone in a recently detoxified heroin addict.
AB  - This case describes a heroin addict who was participating in a placebo-controlled
      randomized trial of naltrexone as an aid to relapse prevention. The patient tried
      to commit suicide by taking a heroin overdose after learning that he was HIV
      positive. He was on naltrexone at the time and, as a result, survived what would
      probably have been a fatal overdose. This case demonstrates that naltrexone can
      have immediate as well as long-term positive effects in persons who are
      attempting to recover from heroin addiction.

PMID- 11455176
TI  - Symptomatic characteristics of parkinsonism and the width of substantia nigra
      pars compacta on MRI according to ischemic changes in the putamen and cerebral
      white matter: implications for the diagnosis of vascular parkinsonism.
AB  - To investigate the significance of vascular lesions as a cause of secondary
      parkinsonism, we analyzed the symptomatic characteristics, the width of the
      substantia nigra pars compacta (SNpc) on MRI and the responsiveness to L-dopa in
      227 parkinsonian cases, excluding those with drug-induced parkinsonism and
      neurodegenerative diseases other than idiopathic Parkinson's disease (IPD). They
      were classified into those without a significant infarct in the basal ganglia (n
      = 144), those with status lacunaris in the putamen (SLP; n = 66) and those with
      confluent white matter hyperintensity signals (CWMH; n = 17). The 4- to 6-Hz
      tremor and cogwheel rigidity were significantly more frequent in cases without
      significant infarct (69%) than those with SLP (50%) and those with CWMH (12%; p <
      0.05). Among cases with 4- to 6-Hz tremor and cogwheel rigidity, the frequency of
      patients with a reduced SNpc width and L-dopa responders did not significantly
      differ between those with SLP (73 and 83%, respectively) and those without
      significant infarct (83 and 86%, respectively), suggesting that the diagnosis for
      most of these cases would be probable IPD. In contrast, among cases without 4- to
      6-Hz tremor and cogwheel rigidity, those with a reduced SNpc width or L-dopa
      responders were significantly less frequent among cases with SLP (25 and 38%,
      respectively) than among those without significant infarct (75 and 71%,
      respectively; p < 0.05). Patients with neither 4- to 6-Hz tremor and cogwheel
      rigidity nor reduction in the SNpc width, for whom the probable diagnosis was
      vascular parkinsonism (VP), were significantly more frequent in cases with SLP
      (26%) and with CWMH (40%) than those without significant infarct (8%), accounting
      for 10.6% of the total parkinsonian cases. These findings suggest that
      parkinsonian cases with SLP or CWMH consist of not only cases with vascular
      lesion-related VP but also IPD in which vascular lesions are not directly related
      to parkinsonism. Absence of 4- to 6-Hz tremor, cogwheel rigidity and the
      reduction in the SNpc width could be indicators for differentiating VP from IPD.

PMID- 11455177
TI  - Switch-over from tolcapone to entacapone in severe Parkinson's disease patients.
AB  - Forty patients affected by severe Parkinson's disease (PD) were treated with
      tolcapone as an adjunctive therapy to L-DOPA, for 3-7 months, until this drug was
      discontinued because of side-effects (2 diarrhoea, one of them with orthostatic
      hypotension, 2 increments of liver enzymes) or because of mandatory indications
      of the European drugs authority. All patients, after 3-6 months of L-DOPA therapy
      adjustments, received entacapone for 3 months again followed by withdrawal. L
      DOPA daily dosage was significantly reduced by tolcapone and entacapone (p = 0.01
      and 0.05). "On" time was increased by 15% during tolcapone treatment (p < 0.05),
      and by 8% during entacapone treatment. "Off" time was decreased by 16% during
      tolcapone and by 7% during entacapone treatment. Entacapone was withdrawn in the
      same patient who experienced diarrhoea and orthostatic hypotension during
      tolcapone because of recurrence of side-effects, in 6 patients because of
      increment of dyskinesias (with hallucinations) and in 1 patients because of
      rhythmic, jerking myoclonus.

PMID- 11455178
TI  - Restless Legs Syndrome among working-aged women.
AB  - A random sample of 200 women, aged 18-64 years, living in a county in mid-Sweden,
      was sent a questionnaire that included questions about sleep habits, symptoms of
      sleepiness and neuropsychiatric complaints. Standardized diagnostic criteria
      determined by the International Restless Legs Syndrome Study Group were used to
      investigate the prevalence of restless legs syndrome (RLS). Possible associations
      between RLS and neuropsychiatric complaints were also investigated. Odds ratios
      for different variables were calculated by means of multivariate logistic
      regression. 11.4% of the women suffered from RLS. Sleep-related complaints were
      more frequent among RLS sufferers than among nonsufferers. Complaints of daytime
      headache were reported 5 times more frequently among RLS sufferers, and there was
      a tendency towards social isolation related to RLS. Subjective problems in
      performing work due to sleepiness were ninefold among the women with RLS. These
      results indicate that RLS together with an association to neuropsychiatric
      symptoms is common among working-aged women.

PMID- 11455179
TI  - Analysis of alpha-synuclein, parkin, tau, and UCH-L1 in a Japanese family with
      autosomal dominant parkinsonism.
AB  - We examined whether autosomal dominant parkinsonism of a Japanese family,
      Sagamihara family, was due to the mutations of alpha-synuclein, parkin, tau, and
      UCH-L1, which have been reported as the causal genes for parkinsonism in other
      families. Restriction-enzyme digestion of polymerase-chain reaction (PCR)
      amplified genomic DNA fragments of alpha-synuclein exons 3 and 4 detected no
      point mutation. PCR-amplification of parkin exons 3, 4, 5, 6 and 7 detected no
      exon deletion. Direct sequencing of PCR-amplified DNA fragments of tau exons 9,
      10, 12, and 13 and intron 10, and of UCH-L1 exon 4 revealed that all these exons
      and intron were normal including a polymorphic nucleotide substitution. These
      results indicated that the parkinsonism of the Sagamihara family seems not to be
      due to previously identified point mutations of alpha-synuclein, tau, or UCH-L1,
      or to exon deletion of parkin.

PMID- 11455180
TI  - Three-dimensional computed tomography angiography and magnetic resonance
      angiography of carotid bifurcation stenosis.
AB  - PURPOSE: To evaluate the role of computed tomography angiography (CTA) and
      magnetic resonance angiography (MRA) in the quantification of atherosclerotic
      stenosis of carotid artery bifurcation in comparison with digital substraction
      angiography (DSA) and Doppler sonography (DS). MATERIALS AND METHODS: Twenty-five
      patients with atherosclerotic disease of the carotid arteries with proven
      stenosis by DSA, had spiral CTA, MRA using two- and three-dimensional time-of
      flight gradient echo techniques, and DS using Doppler flow signal recording
      (total 47 carotid artery bifurcations). The degree of stenosis was measured
      according to the North American Symptomatic Carotid Endarterectomy Trial
      criteria: total occlusion (100%), severe (70-99%), moderate (30-69%) and mild (0
      29%). The degree of stenosis measured by CTA, MRA and DS was compared to DSA,
      used as the gold standard. RESULTS: Ninety-seven percent of MRA measures were
      equivalent to DSA, and 3% were underestimated; 96% of CTA measures were
      equivalent to DSA, and 4% were underestimated; 77% of DS measures were equivalent
      to DSA, 21% were overestimated and 2% were underestimated. CONCLUSIONS: CTA and
      MRA are equally accurate methods in quantifying the degree of carotid bifurcation
      stenosis.

PMID- 11455181
TI  - The cerebrospinal fluid level of glial fibrillary acidic protein is increased in
      cerebrospinal fluid from Alzheimer's disease patients and correlates with
      severity of dementia.
AB  - To gain insight of the underlying mechanisms of astroglial response to
      Alzheimer's disease (AD), the level of glial fibrillary acidic protein (GFAP) in
      cerebrospinal fluid (CSF) from controls and AD subjects were immunochemically
      determined, and the correlation between that level and dementia severity of AD
      patients was evaluated. Means and SD of CSF levels of GFAP for the young control
      group (from 1 to 25 years, mean +/- SD 14.2 +/- 5.0, n = 13) adult control (from
      26 to 55 years, 41.6 +/- 10.1, n = 9) and senescent control (older than 56 years,
      65.4 +/- 8.0, n = 8) were 2.96 +/- 1.04, 2.80 +/- 1.46 and 3.99 +/- 1.55 ng/ml,
      respectively, and the CSF level of GFAP was not dependent on age (ANOVA, p =
      0.17). While that of the AD patient group (n = 27, 70.8 +/- 8.0 years) was 8.96
      +/- 7.80 ng/ml, significantly higher than that of both the all-control (3.19 +/-
      1.39 ng/ml, t test, p < 0.001) and age-matched senescent (3.99 +/- 1.55 ng/ml, t
      test, p < 0.005) control groups. The receiver-operator characteristic (ROC) curve
      revealed that the GFAP concentration at 5 ng/ml in CSF could serve as a cutoff
      value. The CSF level of GFAP in the moderately to severely demented patients
      (MMSE </= 17, 13.2 +/- 9.10 ng/ml, n = 9) was approximately by two-fold higher
      than that of the mildly to moderately demented patients (MMSE >/= 18, 6.85 +/-
      5.76 ng/ml, n = 18; ANOVA, p < 0.05). These findings together with our previous
      report on an increase in the CSF level of apolipoprotein E suggest that
      degeneration and stimulation of astrocytes takes place concurrently in the AD
      brain.

PMID- 11455182
TI  - Corticospinal tract involvement in a variant of Guillain-Barre syndrome.
AB  - To determine the involvement of the corticospinal tract in Guillain-Barre
      syndrome (GBS), we examined central motor conduction in patients with GBS-like
      symptoms and hyperreflexia using a magnetic stimulation technique. The subjects
      were 3 patients who exhibited ascending muscle weakness 2-4 weeks after preceding
      infections. Deep tendon reflexes were exaggerated in all four limbs of the 3
      patients. The results of cerebrospinal fluid examinations revealed protein
      elevation without pleocytosis. The serum anti-GM(1) antibody titer was elevated
      in 2 patients. The results of nerve conduction study revealed axonal motor
      neuropathy and normal F-wave conduction. Central motor conduction time (CMCT) in
      patients with hyperreflexia was significantly delayed compared to that in
      patients with GBS and areflexia (p < 0.001), and the delayed CMCTs were
      significantly improved in the recovery periods (p < 0.001). Although
      hyperreflexia is a controversial symptom in patients with GBS, these findings
      indicate that there is functional corticospinal tract involvement in patients
      with a GBS variant.

PMID- 11455183
TI  - Executive dysfunction in spinocerebellar ataxia type 1.
AB  - Fourteen patients with spinocerebellar ataxia 1 (SCA1) and 11 controls with
      similar mean age and IQ estimates were submitted to a neuropsychological test
      battery comprising tests for IQ, attention, verbal and visuospatial memory as
      well as executive functions. Neuropsychological assessment yielded verbal memory
      and executive dysfunction while tests of visuospatial memory and attention were
      not significantly impaired in SCA1 as compared to controls. Test performance was
      neither related to the repeat length, the age of onset nor the disease duration.
      The profile of cognitive impairment in SCA1 with prominent executive dysfunction
      corresponds to the concept of "frontal-subcortical" dementia that is likely to be
      contingent upon disruption of a cerebrocerebellar circuitry that consists of
      afferent and efferent connections between the prefrontal cortex and the
      cerebellum.

PMID- 11455184
TI  - Daytime sleepiness improvement following bilateral chronic electrical stimulation
      of the subthalamic nucleus in Parkinson's disease.

PMID- 11455185
TI  - Neuroleptic malignant syndrome with hypotonia: a diagnostic challenge.

PMID- 11455186
TI  - Anti-GAD antibodies and breast cancer in a patient with stiff-person syndrome: a
      puzzling association.

PMID- 11455187
TI  - Mycophenolate mofetil: a new immunosuppressive approach. Successful treatment in
      a case of myasthenia gravis associated with incomplete lupus erythematosus
      syndrome and hepatitis C virus infection.

PMID- 11455188
TI  - Insomnia and fronto-basal tumor: a case report.

PMID- 11455189
TI  - Gait ignition failure after unilateral anteromedial pallidotomy.

PMID- 11455190
TI  - Improvement in essential tremor after pure sensory stroke due to thalamic
      infarction.

PMID- 11455191
TI  - Modulation of sympathetic actions on the heart by opioid receptor stimulation.
AB  - The sympathetic nervous system, the most important extrinsic regulatory mechanism
      of the heart, is inhibited postsynaptically and presynaptically by opioid
      peptides produced in the heart via their respective receptors. The cardiac
      actions of beta-adrenergic receptor (beta-AR) stimulation are attenuated by
      activation of the opioid receptor (OR) with OR agonist at ineffective
      concentrations, implying cross-talk between the OR and beta-AR. This cross-talk
      results from inhibition of the Gs protein and adenylyl cyclase of the beta-AR
      pathway by the pertussis toxin-sensitive G protein of the opioid pathway.
      Alterations in cross-talk between these two receptors occur in pathological
      situations to meet bodily needs. In myocardial ischemia, when the sympathetic
      activity is increased, the inhibition of beta-AR stimulation by kappa-opioid
      stimulation is also enhanced, thus reducing the workload, oxygen consumption and
      cardiac injury. Whereas cardiac responsiveness to sympathetic discharges is also
      reduced after chronic hypoxia, the cross-talk between kappa-OR and beta-AR is
      reduced to prevent undue suppression of the sympathetic influence on the heart.
      On the other hand, impairment of the cross-talk may result in abnormality. A lack
      or a significant reduction in the inhibition of beta-AR stimulation by kappa-OR
      stimulation may lead to an excessive increase in cardiac activities, which
      contribute to the maintenance of high arterial blood pressure in spontaneously
      hypertensive rats. Other than opioid peptides, female sex hormone and adenosine
      also inhibit the sympathetic actions on the heart. In addition, sympathetic
      action is also inhibited presynaptically by kappa-opioid peptides via their
      receptor.

PMID- 11455192
TI  - Influence of ovariectomy on ventricular myocyte contraction in simulated
      diabetes.
AB  - We studied the effect of ovariectomy (OVX) on cardiac contraction in myocytes
      maintained under a 'diabetes-simulated high-glucose' environment. Female rats
      were ovariectomized or sham operated (SHAM) and kept for 6 weeks. Isolated
      myocytes were maintained in a diabetes-simulated high [glucose] medium (HG; 25.5
      mM) for 24 h before mechanical properties were measured. Contractile indices
      analyzed included peak shortening (PS), time to PS (TPS), time to 90%
      relengthening (TR90), maximal velocity of shortening and relengthening (+/-
      dL/dt), intracellular Ca2+ fura-2 fluorescence intensity and decay rate (tau).
      Nitric oxide synthase (NOS) activity was also evaluated. OVX myocytes displayed a
      longer TR(90), slower +/- dL/dt, lower fluorescence intensity and higher tau
      (slower decay rate) when compared to SHAM myocytes. In the SHAM group, HG exerted
      diabetes-like contractile dysfunctions, including depressed PS, prolonged TR90,
      reduced fluorescence intensity, higher tau and enhanced NOS activity when
      compared to myocytes maintained in low [glucose] medium (5.5 mM). Interestingly,
      the HG- induced mechanical alterations were significantly exaggerated (TPS, TR90
      and tau), reversed (PS and NOS) or lost (+/- dL/dt and fluorescence intensity) in
      the OVX group. These data suggest that ovarian hormones play a role in the
      regulation of cardiac contractile function, and may have potentially protective
      effects against diabetes-associated cardiac dysfunction.

PMID- 11455193
TI  - Cardiovascular risk in obese and nonobese patients with type 2 diabetes in the
      West Indies.
AB  - OBJECTIVE: To evaluate the impact of obesity on glycemic control and the risk of
      progressing to cardiovascular disease (CVD) in obese and nonobese type 2 diabetic
      patients in primary care settings. METHODS: One hundred and ninety patients (64
      men, 126 women) with type 2 diabetes (mean duration 9.2 years) were studied after
      an overnight fast. Weight, height, waist and hip circumferences and blood
      pressure were measured and blood samples were taken for glucose, glycated
      hemoglobin (HbA(1c)), total cholesterol, triglyceride, high-density lipoprotein
      (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and creatinine
      determinations. RESULTS: About 85% of the patients had HbA(1c) levels > 7.0%, and
      48% had a diastolic blood pressure (BP) >83 mm Hg, while 40% had a total
      cholesterol/HDL-cholesterol ratio greater than 6. The prevalence rates of
      hypercholesterolemia, hypertriglyceridemia, high BP and ratios of total
      cholesterol to HDL-cholesterol between the obese and nonobese patients were
      similar irrespective of sex (p > 0.05). Multiple linear regression analysis
      confirmed that ethnicity, sex, age and duration of diabetes had significant
      impact on the cardiovascular risk in this population. CONCLUSION: Both obese and
      nonobese diabetic patients had poor glycemic control and their risk of CVD was
      not independent of age, sex, ethnicity and duration of diabetes. We suggest
      strict metabolic control and improved diabetes health education at the primary
      care level.

PMID- 11455194
TI  - Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and
      C: the differences and implications in pathogenesis.
AB  - Tumor necrosis factor (TNF) plays a role in the pathogenesis of chronic hepatitis
      B (CHB) and chronic hepatitis C (CHC). The difference in the cytokine responses
      between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may have
      implications in the pathogenesis of these diseases. We performed a comparative
      study to examine the possible differences in the TNF-TNF receptor (TNFR) response
      between CHB and CHC. We studied the cytokine levels of 38 patients with CHB, 40
      patients with CHC and 9 patients with dual hepatitis B and C, and compared them
      with the baseline levels of 12 healthy controls. The plasma levels of TNF-alpha,
      interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and soluble TNFR-1 and 2 (sTNFR
      1 and 2) were quantified by enzyme-linked immunosorbent assays. The expression of
      TNFR-1 and 2 in liver tissues was examined in 30 cases of CHB and 15 cases of CHC
      by semiquantitative reverse transcription polymerase chain reaction. The results
      showed that sTNFR-1 levels correlated with liver inflammation in all patients,
      whereas this correlation was not found with sTNFR-2 or other cytokines. Liver
      inflammation indicators were higher in HCV RNA+ than in HCV RNA- CHC. Most
      significantly, sTNFR-1 levels correlated with liver inflammation in CHB, but not
      in CHC. However, the expression of TNFR-1 and 2 in liver was similar between CHB
      and CHC. These findings suggest that the TNFR signal transduction pathway is
      modulated differently in HBV and HCV infection.

PMID- 11455195
TI  - A novel mutation in the mitochondrial 16S rRNA gene in a patient with MELAS
      syndrome, diabetes mellitus, hyperthyroidism and cardiomyopathy.
AB  - Using RNase protection analysis, we found a novel C to G mutation at nucleotide
      position 3093 of mitochondrial DNA (mtDNA) in a previously reported 35-year-old
      woman exhibiting clinical features of mitochondrial myopathy, encephalopathy,
      lactic acidosis and stroke-like episodes (MELAS) syndrome together with diabetes
      mellitus, hyperthyroidism and cardiomyopathy. The patient also had an A3243G
      mutation in the tRNA(Leu(UUR)) gene and a 260-base pair duplication in the D-loop
      of mtDNA. The fibroblasts of the patient were cultured and used for the
      construction of cybrids using cytoplasmic transfer of the patient's mtDNA to the
      mtDNA-less rho(0) cells. RNA isolated from the cybrids was subjected to RNase
      protection analysis, and a C3093G transversion at the 16S rRNA gene and a MELAS
      associated A3243G mutation of mtDNA were detected. The novel C3093G mutation
      together with the A3243G transition were found in muscle biopsies, hair follicles
      and blood cells of this patient and also in her skin fibroblasts and cybrids. The
      proportion of the C3093G mutant mtDNA in muscle biopsies of the patient was 51%.
      In contrast, the mutation was not detected in three sons of the proband. To
      characterize the impact of the mtDNA mutation-associated defects on mitochondrial
      function, we determined the respiratory enzyme activities of the primary culture
      of fibroblasts established from the proband, her mother and her three sons. The
      proportions of mtDNA with the C3093G transversion and the A3243G transition in
      the fibroblasts of the proband were 45 and 58%, respectively. However, the
      fibroblasts of the proband's mother and children harbored lower levels of mtDNA
      with the A3243G mutation but did not contain the C3093G mutation. The complex I
      activity in the proband's fibroblasts was decreased to 47% of the control but
      those of the fibroblasts of the mother and three sons of the proband were not
      significantly changed. These findings suggest that the C3093G transversion
      together with the A3243G transition of mtDNA impaired the respiratory function of
      mitochondria and caused the atypical MELAS syndrome associated with diabetes
      mellitus, hyperthyroidism and cardiomyopathy in this patient.

PMID- 11455196
TI  - Neuronal NOS inhibitor that reduces oxidative DNA lesions and neuronal
      sensitivity increases the expression of intact c-fos transcripts after brain
      injury.
AB  - In response to oxidative stress, the ischemic brain induces immediate early genes
      when its nuclear genes contain gene damage. Antioxidant that reduces gene damage
      also reduces cell death. To study the mechanism of neuronal sensitivity, we
      investigated the transcription of the c-fos gene after brain injury of the
      ischemia-reperfusion type using focal cerebral ischemia-reperfusion in Long-Evans
      hooded rats. We observed a significant (p < 0.01) increase in c-fos mRNA in the
      ischemic cortex immediately after brain injury. However, the c-fos transcript was
      sensitive to RNase A protection assay (RPA) upon reperfusion. The transcript
      became significantly resistant to RPA (42%, p < 0.03) when 3-bromo-7
      nitroindazole (25 mg/kg, i.p.), known to abolish nitric oxide, gene damage and
      neuronal sensitivity, was injected. Our data suggest that neuronal nitric oxide
      synthase and aberrant mRNA from genes with oxidative damage could be associated
      with neuronal sensitivity.

PMID- 11455197
TI  - Isolation and partial characterization of a 46-kd allergen of Bermuda grass
      pollen.
AB  - Cyn d Bd46K, a 46-kD component of Bermuda grass (Cynodon dactylon) pollen, had
      been identified as an allergenic constituent. In the present study two
      dimensional (2D) gel electrophoresis illustrated the presence of five acidic
      isoforms in Cyn d Bd46K, and this molecule was purified by monoclonal antibody
      (MAb) affinity chromatography for further characterization. Using a digoxigenin
      labeled lectin-binding assay, the elucidating protein was disclosed to be a
      glycoprotein with terminal mannose. The involvement of a carbohydrate moiety in
      the allergenicity and antigenicity of the elucidated molecule was demonstrated
      with sodium-periodate-treated Cyn d Bd46K, which reduced binding to its specific
      MAb and human IgE. We were unable to identify the N-terminal amino acid sequences
      of Cyn d Bd46K, but some internal amino acid sequences were disclosed by
      microsequencing some fragments cleaved by Achromobacter protease I and
      fractionated by reversed-phase column chromatography. The amino acid sequences of
      4 identified Cyn d Bd46K internal peptide fragments were found to be 25-71%
      identical with that of cytochrome c oxidase III from corn grass pollen. The
      present study provided important information for future experiments on the
      molecular cloning of the elucidated allergen.

PMID- 11455198
TI  - The association of heterotrimeric GTP-binding protein (Go) with microtubules.
AB  - The heterotrimeric GTP-binding regulatory proteins (G proteins) play an important
      role in the regulation of membrane signal transduction. Recently, we identified
      the association of Go protein with mitotic spindles. Here we have investigated
      the relationship between Go protein and microtubules. We used temperature
      dependent reversible assembly and taxol methods to purify microtubules from
      bovine brains. Goalpha and Gbeta proteins were identified in the microtubular
      fraction by both methods. The Goalpha subunit in the microtubular fraction could
      be ADP ribosylated by pertussis toxin. Co-immunoprecipitation data also revealed
      that Go protein can interact with microtubules. Exogenous Go protein could be
      incorporated into the assembled microtubular fraction, and 5 microg/ml (60 nM) of
      Go protein inhibited 40% of microtubule assembly. Western blot analysis of
      Goalpha-1 and Goalpha-2 in microtubular fractions showed that only Goalpha-1 is
      associated with microtubules. We conclude that the Goalpha-1betagamma proteins
      are associated with microtubules and may play some role in regulating the
      assembly and disassembly of microtubules.

PMID- 11455199
TI  - Oxygen-induced seizures and inhibition of human glutamate decarboxylase and
      porcine cysteine sulfinic acid decarboxylase by oxygen and nitric oxide.
AB  - The recombinant forms of the two human isozymes of glutamate decarboxylase, GAD65
      and GAD67, are potently and reversibly inhibited by molecular oxygen (Ki = 0.46
      and 0.29 mM, respectively). Inhibition of the vesicle-associated glutamate
      decarboxylase (GAD65) by molecular oxygen is likely to result in incomplete
      filling of synaptic vesicles with gamma-aminobutyric acid (GABA) and may be a
      contributing factor in the genesis of oxygen-induced seizures. Under anaerobic
      conditions, nitric oxide inhibits both GAD65 and GAD67 with comparable potency to
      molecular oxygen (Ki = 0.5 mM). Two forms of porcine cysteine sulfinic acid
      decarboxylase (CSADI and CSADII) are also sensitive to inhibition by molecular
      oxygen (Ki = 0.30 and 0.22 mM, respectively) and nitric oxide (Ki = 0.3 and 0.2
      mM, respectively). Similar inhibition of glutamate decarboxylase and cysteine
      sulfinic acid decarboxylase by two different radical-containing compounds (O2 and
      NO) is consistent with the notion that these reactions proceed via radical
      mechanisms.

PMID- 11455200
TI  - Lamp-1 is upregulated in human glioblastoma cell lines induced to undergo
      apoptosis.
AB  - Lysosome-associated membrane protein (LAMP)-1, one of the major protein
      components of the lysosomal membrane, is upregulated in the human glioblastoma
      cell lines, U-373 MG and LN-Z308, which undergo cisplatin-induced apoptosis.
      These human brain tumor cell lines demonstrated apoptosis in response to
      cisplatin/nifedipine treatment. Both cell lines demonstrated an apoptotic
      response by more than one criterion. Apoptosis was demonstrated by DNA
      fragmentation techniques such as DNA laddering, ApopTag in situ labeling, and an
      ELISA-based method of detecting liberated oligosomes. These cells also had
      characteristic morphologic changes and upregulation of bax consistent with
      apoptosis. LAMP-1 expression at the protein and mRNA level was examined and found
      to increase with cisplatin/nifedipine treatment. LAMP-1 expression was examined
      using indirect immunofluorescent staining, Northern blot analysis and Western
      blot analysis. The finding of an augmentation of LAMP-1 in these cells induced to
      die is enigmatic. These findings raise the possibility of LAMP-1 involvement in
      the apoptotic process.

PMID- 11455201
TI  - Relative contributions of cyclooxygenase- and cytochrome P450 omega-hydroxylase
      dependent pathways to hypoxic dilation of skeletal muscle resistance arteries.
AB  - This study determined the contribution of prostanoids, cytochrome P450 (CP450) 4A
      enzyme metabolites of arachidonic acid, and other potential mediators of hypoxic
      dilation of isolated rat skeletal muscle resistance arteries. Gracilis arteries
      (GA) were viewed via television microscopy and dilator responses to hypoxia
      (reduction in superfusate and perfusate PO2 from approximately 145 to
      approximately 40 mm Hg) were measured with a video micrometer. Hypoxic dilation
      of gracilis arteries was severely impaired by either endothelium removal or
      cyclooxygenase inhibition with indomethacin, but not by nitric oxide synthase
      inhibition with L-NAME. Treatment of GA with 17-octadecynoic acid (17-ODYA) alone
      to inhibit CP450 4A enzymes significantly reduced hypoxic dilation from control
      levels. Treatment of vessels with N-methylsulfonyl-6-(2
      proparglyoxyphenyl)hexanoic acid (MS-PPOH) to inhibit the production of
      epoxyeicosatrienoic acids (EETs) did not alter hypoxic dilation, although
      treatment with dibromo-dodecenyl-methylsulfimide (DDMS) to inhibit 20
      hydroxyeicosatetraenoic acid (20-HETE) production had similar effects as 17-ODYA.
      Treatment of GA with 6(Z),15(Z)-20-HEDE, a competitive antagonist of the actions
      of 20-HETE, mimicked the effects of 17-ODYA and DDMS treatment on hypoxic
      dilation. These results suggest that hypoxic dilation of skeletal muscle
      resistance arteries primarily represents the effects of enhanced prostanoid
      release from vascular endothelium, although a contribution of reduced 20-HETE
      production via CP450 omega-hydroxylase enzymes also regulates hypoxic dilation of
      these vessels.

PMID- 11455202
TI  - Enhanced gene transfer to rabbit jugular veins by an adenovirus containing a
      cyclic RGD motif in the HI loop of the fiber knob.
AB  - Gene therapy using recombinant adenoviral vectors represents a promising
      therapeutic tool to prevent vein graft stenosis, the main complication of
      coronary artery bypass grafting. However, the low transduction efficiency of
      vascular smooth muscle cells and endothelial cells (EC) is a potential
      limitation, presumably due to the low levels of functional adenovirus receptor
      (coxsackie:adenovirus receptor; CAR). Designing vectors specifically targeted to
      alpha(v) integrins is a strategy that might overcome the poor expression of CAR
      in vascular smooth muscle cells and EC. RGD, a receptor-binding motif that can
      interact with alpha(v) integrins, was inserted into the HI loop and at the C
      terminus of the adenoviral fiber protein in two separate adenovirus vectors
      encoding a beta-galactosidase reporter gene. Av1nBgCRGD (C-terminus) and
      Av1nBgHIRGD (HI loop) were evaluated in EC in culture and in jugular vein organ
      culture. Transduction of primary rat and rabbit EC with Av1nBgHIRGD was
      significantly more efficient when compared to Av1nBgCRGD or Av1nBg. Transduction
      of mouse, rat and rabbit jugular veins in organ culture using Av1nBg showed that
      adenovirus-mediated gene expression was greatest in rabbit jugular veins compared
      to rat and mouse veins. Av1nBgHIRGD augmented gene expression approximately four
      fold in rabbit jugular veins when compared to Av1nBg. Histochemical analysis
      showed that numerous EC but few smooth muscle cells were transduced at all vector
      concentrations. A substantial number of adventitial fibroblasts were transduced
      only at the highest vector concentrations of Av1nBgHIRGD. These findings
      demonstrate that integrin-targeted vectors allow for enhanced gene delivery to
      veins and strengthen the viability of adenoviral-mediated gene transfer of
      therapeutic transgenes to human veins prior to vein grafting.

PMID- 11455203
TI  - Increased store-operated Ca2+ entry into contractile vascular smooth muscle
      following organ culture.
AB  - Ca2+ inflow via store-operated Ca2+ channels was investigated in rings of rat
      tail and basilar arteries kept in serum-free organ culture, which is known to
      preserve the contractility of the vascular smooth muscle. After culture for 3-4
      days, Ca2+ release from intracellular stores in response to caffeine (20 mM) was
      augmented 2- to 4-fold. Following depletion of intracellular Ca2+ stores by
      caffeine and thapsigargin (10 microM), addition of Ca2+ (2.5 mM) caused an
      increase in the intracellular Ca2+ concentration which was 2-3 times greater in
      cultured than in freshly dissected rings, and was not affected by verapamil (10
      microM). In contrast, L-type Ca2+ channel currents were decreased by 20% after
      culture. While freshly dissected rings developed no or very little force in
      response to the addition of Ca2+ after store depletion, cultured rings developed
      42% (tail artery) and 60% (basilar artery) of the force of high-K+-induced
      contractions. These contractions in cultured vessels were insensitive to
      verapamil but could be completely relaxed by SKF-96365 (30 microM). Store
      depletion by caffeine increased the Mn2+ quench rate 3- to 4-fold in freshly
      dissected as well as cultured tail artery, while there was no increase in freshly
      dissected basilar artery, but a 3-fold increase in cultured basilar artery.
      Uptake of Ca2+ into intracellular stores was twice as rapid in cultured as in
      freshly dissected tail artery. This study shows that organ culture of vascular
      smooth muscle tissue causes changes in Ca2+ handling, resembling the pattern seen
      in dedifferentiating smooth muscle cells in culture, although contractile
      properties are maintained.

PMID- 11455204
TI  - P2X receptor immunoreactivity in different arteries from the femoral, pulmonary,
      cerebral, coronary and renal circulations.
AB  - The expression of the seven P2X receptor subunits (P2X1-7) in the rat vascular
      system was determined using subtype-selective antibodies. Arteries of different
      sizes (from arterioles to conduit vessels) from a range of vascular beds were
      used to give an overview of receptor expression. P2X1 receptor immunoreactivity
      was detected in the smooth muscle layer of arteries. The relative level of P2X1
      receptor immunoreactivity was dependent on the size of the artery and the
      vascular bed; expression was highest in small and medium arteries. P2X4 receptors
      were detected in all arteries; once again, the relative level of expression was
      dependent on the size of the artery and the vascular bed. P2X5 receptor
      immunoreactivity was barely detectable in most arteries studied. P2X7 receptor
      immunoreactivity was generally punctate and associated with the outer adventitial
      layer. Immunoreactivity for P2X2, P2X3 and P2X6 receptors was not detected in
      arteries. These results demonstrate that arteries express multiple P2X receptor
      subunits and that there is a heterogeneity in the level of expression. The
      properties of artery P2X receptors correspond to homomeric P2X1 receptors, and
      the function of P2X4 and P2X5 receptor subunits in arteries is unclear.

PMID- 11455205
TI  - Monocyte chemotactic protein 1 amplifies serotonin-induced vascular smooth muscle
      cell proliferation.
AB  - Monocyte chemotactic protein 1 (MCP-1), which is synthesized by vascular cells,
      is a chemoattractant for monocytes and has been implicated in a wide range of
      acute and chronic inflammatory processes characterized by monocyte infiltration,
      including atherosclerosis. However, it is unclear whether MCP-1 is able to
      modulate vascular smooth muscle cell (VSMC) proliferation. We assessed the effect
      of MCP-1 on VSMC proliferation and its interaction with serotonin (5-HT), a
      mitogen for VSMCs. Growth-arrested VSMCs were stimulated with different
      concentrations of MCP-1 (25-200 ng/ml) and 5-HT (5 and 50 microM) in serum-free
      medium. DNA synthesis in VSMCs was measured by [3H]thymidine incorporation. 5-HT
      at concentrations of 5 and 50 microM significantly stimulated DNA synthesis by
      1.8- and 2.1-fold over the control value, respectively (p < 0.0001). However, MCP
      1 at the concentrations tested did not have any significant effect on DNA
      synthesis. Even though MCP-1 (50 ng/ml) by itself is not mitogenic, when added to
      5-HT, it significantly amplified the mitogenic effect of 5-HT compared with that
      of 5-HT alone (p < 0.0001). The 5-HT2A receptor antagonist sarpogrelate (10
      microM) and its major metabolite M-1 (0.1 microM), pertussis toxin (10 ng/ml),
      Src family protein tyrosine kinase (PTK) inhibitor PP2 (1 microM), protein kinase
      C (PKC) inhibitor Ro31-8220 (0.1 microM) and mitogen-activated protein kinase
      (MAPK) kinase inhibitor PD098059 (10 microM) significantly inhibited the
      mitogenic effect of 5-HT and its interaction with MCP-1. Anti-MCP-1 antibody (2
      microg/ml) and the Janus kinase 2 (JAK2) inhibitor AG490 (10 microM)
      significantly inhibited the interaction of MCP-1 with 5-HT. Further, the
      amplified mitogenic effect of 5-HT with MCP-1 was completely reversed by the
      combined use of sarpogrelate with anti-MCP-1 antibody. Our results suggest that
      MCP-1 amplifies the mitogenic effect of 5-HT on VSMCs. The mitogenic effect of 5
      HT may be mediated by the G protein-Src family PTK-PKC-MAPK pathway. The
      activation of the JAK2/signal transducer and activator of transcription 3 pathway
      by MCP-1 in addition to the MAPK pathway by 5-HT may explain the potentiating
      effect of MCP-1 on 5-HT-induced mitogenesis.

PMID- 11455206
TI  - The internal redox balance of the cells influences the metabolism of lipids of
      dietary origin by J774 macrophages: implications for foam cell formation.
AB  - The effects of chylomicron remnants on lipid accumulation in J774 macrophages,
      and the incorporation of radioactivity from remnant lipids radiolabelled with
      [3H]oleate into cellular lipids was investigated. After 24 h of incubation with
      chylomicron remnants, there was considerable accumulation of lipid within the
      cells as assessed by staining with oil red O, indicating that the particles
      induce the formation of foam cells. Fatty acids released from the radiolabelled
      remnant lipids after uptake were found to be incorporated into cellular
      triacylglycerol (52%), phospholipid (37%) and cholesteryl ester (8%), but at
      higher remnant concentrations, the proportion used for triacylglycerol formation
      increased (up to 73%). When the macrophages were shifted into a pro-oxidising or
      pro-reducing state by incubation (24 h) with CuSO4 (2.5 microM) or N
      acetylcysteine (5 mM), respectively, the incorporation of [3H]oleate from remnant
      lipid into cellular triacylglycerol and phospholipid was increased by 20-30% in
      the more oxidised as compared with the more reduced cells. These findings
      indicate that exposure of J774 macrophages to chylomicron remnants leads to the
      accumulation of lipid within the cells, and that this process is enhanced by pro
      oxidising conditions. We conclude, therefore, that both lipids of dietary origin
      and the redox balance within macrophages may have a significant role in the
      induction of foam cell formation.

PMID- 11455207
TI  - Biodegradation of the copolymeric polylactide stent. Long-term follow-up in a
      rabbit aorta model.
AB  - The behavior of biodegradable polylactide as a stent material has not yet been
      fully established in small vessels such as arteries with a diameter <3 mm. The
      aim of this study was to investigate the long-term effect of a copolymeric
      polylactide (PLA96) stent. Appropriately sized spiral PLA96 stents were implanted
      into the infrarenal aortas of 20 rabbits. Intraoperative systemic heparinization
      (150 IU/kg), perioperative subcutaneous enoxaheparin sodium (10 mg), ticlopidine
      (250 mg/day) for 1 month, and acetosalicylic acid (12.5 mg/day) were continuously
      administered. Animals were euthanized according to a fixed timetable for up to 34
      months for histologic and scanning-electron-microscopic assessment.
      Endothelialization was complete within 1 month. In 2 of the 3 aortas sampled 3
      months after implantation, a mild inflammatory reaction was visible, with no sign
      of granulomatous or foreign-body reaction in the vessel wall. Instead, in 1
      sample examined at the same time point, neointimal chondroid metaplasia was
      detected. After 6 months, inflammatory reaction declined in the vessel wall.
      Hydrolyzation of the stent was histologically evident at 12 months, with mild
      foreign-body reaction detectable in 2 of 5 aortas sampled at this time point. The
      stent disintegrated without fragmentation by 24 months, as it was gradually
      replaced by fibrosis. The vessel lumen remained patent at all time points. We
      conclude that the PLA96 stent degraded with minimal tissue response within 24
      months. PLA96 may thus be a promising stent core material for small vessels in
      the future, although further investigation is needed to establish its final
      biocompatibility.

PMID- 11455208
TI  - Downregulation of angiotensin-converting enzyme by tumor necrosis factor-alpha
      and interleukin-1beta in cultured human endothelial cells.
AB  - Angiotensin-converting enzyme (ACE) and cytokines are considered to play an
      important role in the pathophysiology of cardiovascular diseases such as
      atherosclerosis. In the present study, the effects of the cytokines tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) on ACE in
      cultured human umbilical vein endothelial cells (HUVECs) was studied. TNF-alpha
      (0.1-10 ng/ml) and IL-1beta (0.1-10 ng/ml) caused a dose- and time-dependent
      decrease in the amount of ACE in intact endothelial cell membranes and decreased
      levels of ACE mRNA. TNF-alpha and IL-1beta activated p44/42 and p38 mitogen
      activated protein kinases (MAPKs) in HUVECs; this was inhibited by the specific
      inhibitors of these kinases, PD98059 and SB202190, respectively. Pretreatment of
      endothelial cells with the specific p38 MAPK inhibitor SB202190 (5 microM) or
      hydrocortisone (5 microM) partly reversed the suppression of ACE by TNF-alpha or
      IL-1beta, whereas the specific p44/42 MAPK inhibitor PD98059 (40 microM) was
      without effect. Vascular endothelial growth factor (1 ng/ml) caused an increase
      in membrane-bound ACE and ACE mRNA levels which was inhibited by pretreatment of
      the cells with TNF-alpha (1 ng/ml) or IL-1beta (1 ng/ml). In summary, the
      cytokines TNF-alpha and IL-1beta downregulated ACE in cultured human endothelial
      cells, which effect was probably mediated by the p38 MAPK pathway. Downregulation
      of ACE by TNF-alpha and IL-1beta locally in the vascular wall may be a
      counterbalancing mechanism in inflammatory processes such as atherosclerosis,
      leading to decreased production of angiotensin II and accumulation of bradykinin.

PMID- 11455209
TI  - Inhibition by eicosapentaenoic acid of oxidized-LDL- and lysophosphatidylcholine
      induced human coronary artery smooth muscle cell production of endothelin.
AB  - The objectives of the present study were (1) to determine whether oxidized low
      density lipoprotein (LDL) and lysophosphatidylcholine (lyso-PC), a major
      phospholipid component of oxidized LDL, stimulate the production of endothelin-1
      (ET)-1 in cultured human coronary artery smooth muscle cells (SMCs), and (2) to
      examine the possible effect of an antiatherogenic agent, eicosapentaenoic acid
      (EPA), on oxidized-LDL- and lyso-PC-stimulated ET-1 production in these cells.
      Oxidized LDL (10-50 microg/ml) and lyso-PC (10(-7) to 10(-5) mol/l) stimulated ET
      1 production in a concentration-dependent manner. By contrast, the effects of
      native LDL and phosphatidylcholine were modest or absent. Lyso-PC (10(-7) to 10(
      5) mol/l) and oxidized LDL (10-50 microg/ml) significantly induced particulate
      protein kinase C (PKC) activation. Lyso-PC- and oxidized-LDL-stimulated ET-1
      production was significantly inhibited by PKC inhibitor, PKC (19-36). EPA (80-160
      micromol/l) clearly suppressed ET-1 production stimulated by oxidized LDL and
      lyso-PC in a concentration-dependent manner. Furthermore, EPA (160 micromol/l)
      significantly inhibited lyso-PC (10(-5) mol/l)- and oxidized LDL (50 microg/ml)
      induced particulate PKC activation. Results suggest that oxidized LDL and lyso-PC
      stimulate ET-1 production by a mechanism involving activation of PKC, and that
      EPA suppresses ET-1 production stimulated by lyso-PC as well as oxidized LDL
      probably through the modulation of PKC in human coronary artery SMCs. EPA may
      exert an antiatherosclerotic effect, in part, through these mechanisms.

PMID- 11455210
TI  - Cell-mediated delivery of fibroblast growth factor-2 and vascular endothelial
      growth factor onto the chick chorioallantoic membrane: endothelial fenestration
      and angiogenesis.
AB  - Fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor (VEGF)
      exert their angiogenic activity by interacting with endothelial cells in a
      distinct manner. In this study, we investigated the morphological features of
      endothelial cells of the chick embryo chorioallantoic membrane (CAM)
      microvasculature after stimulation with FGF2 or VEGF. In order to provide a
      continuous delivery of the growth factor, we utilized a recently developed
      gelatin sponge/CAM assay in which a limited number of FGF2- or VEGF-transfected
      cells were adsorbed onto gelatin sponges and applied on the top of the CAM on day
      8 of development. Their angiogenic activity was compared to that exerted by a
      single bolus of the corresponding growth factor. All the angiogenic stimuli
      induced a comparable vasoproliferative response, as demonstrated by the
      appearance of similar numbers of immature blood vessels within the sponge on day
      12. No angiogenic response was observed in CAMs implanted with the corresponding
      parental cell lines or vehicle. Electron microscopy demonstrated that VEGF
      overexpressing cells modified the phenotype of the endothelium of the blood
      vessels at the boundary between the implant and the surrounding CAM mesenchyme.
      The endothelial lining of 30% of these vessels showed segmental attenuations, was
      frequently interrupted and became fenestrated, mimicking what is observed in
      tumor vasculature. In contrast, the vessels consisted of continuous endothelium
      sealed by tight junctions in all the other experimental conditions. These results
      indicate that FGF2 and VEGF interact with endothelial cells of the CAM in a
      distinct manner. Both growth factors induce a potent angiogenic response, but
      only VEGF delivered in a continuous manner by its transfectants can modify the
      phenotype of the otherwise quiescent endothelium of CAM blood microvessels. The
      gelatin sponge/CAM assay may constitute a new model to study the mechanisms
      leading to endothelial fenestration in tumor growth.

PMID- 11455213
TI  - Early versus deferred hormonal treatment for asymptomatic prostate cancer.
AB  - There are two different clinical scenarios in which a decision on hormonal
      therapy either initially after diagnosis of deferred until the occurrence of
      signs and symptoms for presently asymptomatic prostate cancer is needed: A more
      recently described cohort of men with prostate cancer who underwent definitive
      therapy for putatively curable disease experiencing a rising PSA (biochemical
      relapse / progression), and a more classical group of men with prostate cancer
      who were unwilling or unfit to undergo local therapy with curative intent. Long
      term hormonal treatment will expose patients to the risk of substantial adverse
      side effects such as muscle wasting, chronic fatigue, osteoporosis and others, in
      addition to an overall increase in treatment costs. On the other hand, a
      potential prolongation of survival and a delay in the development of clinical
      symptoms may serve as arguments for early treatment. A number of studies have
      been conducted in which early hormonal treatment delays the time to progression
      and reduces the cancer-related complication rate such as urinary obstruction and
      bone fractures. However, results on overall survival remain inconclusive and
      quality-of-life issues will become more and more important in light of the
      extended life span of patients with asymptomatic prostate cancer in recent years.
      Ongoing clinical trials such as EORTC 30991 are needed to provide further
      information on this important issue.

PMID- 11455214
TI  - Role of interstitial brachytherapy in the treatment of malignant disease.
AB  - Interstitial brachytherapy was first applied using radium needles, with minimum
      protection of physicians and nurses. Modern techniques involve the use of
      radionuclide (192)Ir as the source used in computer-controlled remote
      afterloading machines, which can deliver a high dose rate (HDR). Treatment
      planning is also undertaken with the use of computers and anatomical cross
      section images using CT, ultrasound and MRI. This review presents these modern
      techniques for tumors of a series of body sites: prostate, head and neck, breast,
      bladder, brain, and for soft-tissue sarcomas. Low dose rate (LDR) interstitial
      brachytherapy techniques are also included in this review since in some body
      sites there is a choice between HDR and LDR.

PMID- 11455215
TI  - Photodynamic therapy of head and neck cancer.
AB  - Photodynamic therapy (PDT) is an alternative treatment option for tumours of the
      head and neck. The principle of PDT is based on a photochemical reaction which is
      initiated by light activation of a photosensitizing drug causing tumour cell
      death. PDT damage heals mainly by regeneration rather than scarring. Due to this
      organpreserving principle of PDT, important structures are maintained with very
      good functional and cosmetic outcome. This article will review the principle of
      PDT and the different indications for PDT of tumours of the head and neck,
      focusing on small and advanced tumours of the oral cavity and the larynx as well
      as papillomatosis of the larynx. A critical review on the literature will be
      accomplished.

PMID- 11455216
TI  - Clinical relevance of the plasminogen activator inhibitor type 1--a multifaceted
      proteolytic factor.
AB  - The plasminogen activator inhibitor type-1 (PAI-1) is a multifaceted proteolytic
      factor. It not only functions as an inhibitor of the protease uPA (urokinase-type
      plasminogen activator), but also plays an important role in signal transduction,
      cell adherence, and cell migration. Thus--an apparent paradox considering its
      name--although it inhibits uPA during blood coagulation, it actually promotes
      invasion and metastasis. In the early 1990s, clinical evidence associated
      elevated PAI-1 levels in tumor tissue with poor clinical outcome in primary
      breast cancer. These clinical data have since been supported by experimental
      evidence that the concerted action of uPA, its cell surface receptor uPA-R, and
      PAI-1 facilitates invasion and metastasis. The strong prognostic impact of PAI-1
      in primary breast cancer has been validated by international research groups
      assessing fresh tumor tissue extracts by ELISA. There is clinical evidence that
      high-risk patients with elevated PAI-1 in their tumor benefit from adjuvant
      systemic therapy. uPA also has a strong prognostic impact in primary breast
      cancer. In node-negative breast cancer, risk-group selection for adjuvant
      systemic therapy based on tumor levels of both PAI-1 and uPA is close to routine
      clinical use. Also in other malignancies such as ovarian, esophageal, gastric,
      colorectal or hepatocellular cancer, elevated PAI-1 is associated with tumor
      aggressiveness and poor patient outcome. This abundant clinical evidence
      implicating PAI-1 as a key factor for tumor invasion and metastasis renders it a
      promising target for tumor therapy. Novel therapeutic approaches targeting the
      PAI-1/uPA interaction are already in pre-clinical testing.

PMID- 11455217
TI  - Surgical management of single and multiple brain metastases: results of a
      retrospective study.
AB  - BACKGROUND: Advancement in diagnosis and treatment of various cancer entities led
      to an increasing incidence of brain metastases in the last decades. Surgical
      excision of single and multiple brain metastases is one of the central treatment
      options beside radiotherapy, radiosurgery and chemotherapy. To evaluate the
      benefit of surgery with/without whole-brain radiation therapy (WBRT) in single
      brain metastases and the influence of image guidance for brain metastases
      resection, 104 patients were retrospectively evaluated for post-operative
      outcome. PATIENTS AND METHODS: Between January 1994 and December 1999 150
      patients were surgically treated for brain metastases at the Department of
      Neurosurgery at the Technical University of Dresden. Outcome could be evaluated
      in 104 patients with respect to special treatment strategies and survival time
      (69 patients with single and 35 patients with multiple lesions). RESULTS: Most
      metastases originated from primary lung and breast tumours. Karnofsky performance
      score improved on average by 10 after surgery. The extent of the extracerebral
      tumour burden was the main influence on survival time. Patients' age below 70
      years was combined with prolonged survival time (median survival time, MST: 4.5
      months vs. 7 months). Patients with solitary cerebral metastasis had a MST of 16
      months, whereas patients with singular lesions had a MST of 7 and 4 months,
      depending on the extent of the extracerebral tumour growth. Additional post
      operative WBRT with 30 Gy was combined with an increase in MST in patients with
      single brain metastasis (surgery + WBRT: MST 13 months; surgery only: MST 8
      months). In addition, the rate of recurrent cerebral tumour growth was distinctly
      higher in the non-WBRT group. Neuronavigation did not significantly improve post
      operative survival time. In 80% of patients extracerebral tumour growth limited
      patients' survival. CONCLUSION: Surgery is an initial treatment option in
      patients with single and multiple brain metastases especially with large tumours
      (> 3 cm). Post-operative WBRT seems to prolong survival time in patients with
      single brain metastasis by decreasing local and distant tumour recurrence.
      Neuronavigational devices permit a targeted approach. Multiple processes can be
      extirpated in one session without prolonging the hospitalisation time for the
      patient. However, neuronavigational devices cannot assure complete tumour
      resection.

PMID- 11455218
TI  - Topotecan chemotherapy in patients with breast cancer and brain metastases:
      results of a pilot study.
AB  - BACKGROUND: Symptomatic brain metastases occur in approximately 10-15% of
      patients suffering from breast cancer and are linked to a clear deterioration of
      the patient's condition. Although radiotherapy is recommended as a primary
      therapy, the optimal management remains controversial. To evaluate the role of
      topotecan as a primary chemotherapy for brain metastases, we performed a pilot
      study in patients with metastatic breast cancer. PATIENTS AND METHODS: 24
      patients with newly diagnosed, bidimensionally measurable brain metastases
      received topotecan, 1.5 mg/m(2) day, 30-min infusion for 5 days every 3 weeks. A
      total of 93 courses of therapy were administered (range 1-11, median 3 courses
      per patient). Prior radiotherapy was excluded. Most of the patients had received
      prior adjuvant or palliative chemotherapy. RESULTS: 3/24 patients were withdrawn
      from the study for various reasons, 16/24 patients could be evaluated in terms of
      their response to therapy; 1 and 5 patients showed complete and partial response
      to therapy, respectively, and 5 patients had a stable condition. The median time
      of survival was 6.25 months. Hematologic toxicity was the major side effect,
      nonhematologic side effects occurred rarely and were tolerable. CONCLUSIONS: Our
      results demonstrate that primary chemotherapy with topotecan is an effective and
      well-tolerated treatment for patients with breast cancer and CNS metastases.
      Based on this pilot study, future clinical protocols should be developed
      including multimodal treatment strategies (i.e. radiotherapy).

PMID- 11455219
TI  - Management of inoperable carcinoma of the breast by curative radiotherapy and
      chemo-hormonotherapy.
AB  - BACKGROUND: The aim of this study was to evaluate local control and its relation
      to survival in patients with locally advanced breast cancer treated with curative
      irradiation and systemic therapy. PATIENTS AND METHODS: 240 patients with
      unresectable breast cancer were treated with curative radio- and chemo- or
      hormonotherapy from 1990-1995. The frequency of distant dissemination and the
      overall survival of patients with and without complete local control were
      compared. RESULTS: Complete local control was achieved in 63% of patients.
      Complete local control correlated with decrease of distant metastases and
      increase of survival in comparison with patients without complete local control.
      CONCLUSION: Radiotherapy without surgery provides insufficient local control in
      patients with locally advanced breast cancer. Complete local control is an
      important factor for prevention of distant dissemination and for survival.

PMID- 11455220
TI  - Effects of inpatient rehabilitation on health-related quality of life in breast
      cancer patients.
AB  - BACKGROUND: Major endpoint for the assessment of a complex inpatient
      rehabilitation program is the health-related quality of life. In a prospective
      longitudinal study we evaluated the subjective well-being of breast cancer
      patients by different methods. PATIENTS AND METHODS: 183 breast cancer patients
      were asked to complete six different questionnaires at three different time
      points: t1: start of treatment, t2: end of treatment, t3: 3 months after t2.
      RESULTS: In the Hospital Anxiety and Depression Scale (HADS-D) we observed high
      mean scores for anxiety (8.73) and depression (5.55), as compared to a healthy
      control population (5.8 and 3.34, respectively). There was a significant
      improvement for both scores at t2 (6.84 and 4.77, respectively) and for anxiety
      at t3 (7.68). This was confirmed by the FBK questionnaire showing a significant
      decrease of the psychological distress in the t1/t2 and t1/t3 time periods as
      well. The global health score of the QLQ-C30 instrument increased significantly
      at the end of the rehabilitation and was maintained at the 3-month follow-up.
      This was true for most of the functional subscales as well. Older widowed women
      with 3-4 accompanying diseases had the most profit from the program. Using the
      Perceived Adjustment to Chronic Illness Scale (PACIS), we observed significantly
      less effort of coping with the illness at t2 and t3. CONCLUSIONS: At the end of a
      complex rehabilitation program for breast cancer patients, the health-related
      quality of life improved in several domains. While after a 3-month follow-up the
      scores were still better than before the treatment, anxiety and depression
      increased again. Therefore, the good results of the rehabilitation program should
      be maintained by continuous ambulatory treatment.

PMID- 11455221
TI  - Prognostic impact of molecular analyses in adenoid cystic carcinomas of the
      salivary gland.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) of the salivary gland is a generally
      slow-growing but highly malignant neoplasm with a remarkable capacity for
      recurrence. Prognosis is greatly influenced by the histological subtype (tubular,
      cribriform or solid), presence of tumour at the margins, anatomic size, and lymph
      node metastases. However, none of these parameters has proven to be an
      unequivocal predictor of disease activity. Therefore, the current study was
      undertaken to investigate the prognostic value of molecular markers. PATIENTS AND
      METHODS: Samples from 22 patients, including 4 patients with recurrent disease,
      were included in the study. By means of immunohistochemistry, the staining
      pattern of p53, bcl-2, P-glycoprotein, glutathione S-transferase, and
      topoisomerase as well as sequence analyses of p53 were performed. These molecules
      were chosen because of their proven association with poor prognosis and therapy
      resistance in other malignancies. RESULTS: Homozygous p53 mutations were found in
      all of the 4 recurrent tumors. The other proteins were detected in some tumors,
      but showed no correlation with histological subtype or recurrence of tumor.
      CONCLUSION: The results of the current study emphasize the prognostic value of a
      p53 alteration as an independent prognostic marker. Further, it could be
      demonstrated for the first time that proteins known for their association with
      radio- and chemotherapy resistance can be overexpressed in some ACCs suggesting
      that those molecules could influence the outcome of new therapeutical approaches.

PMID- 11455222
TI  - Neoadjuvant radio-chemotherapy of adenocarcinoma of the oesophagogastric
      junction.
AB  - BACKGROUND: Recently, neoadjuvant radio-chemotherapy has been demonstrated to
      induce tumour remission and to prolong survival of patients with locally advanced
      adenocarcinoma of the oesophagogastric junction.The present study was performed
      to re-evaluate these data. PATIENTS AND METHOD: A non-randomised trial of
      multimodal treatment was conducted in order to investigate histopathologic
      response and survival of patients with adenocarcinoma of the oesophagogastric
      junction. Treatment consisted of 2 courses of combined chemotherapy with 15 mg/kg
      5-fluorouracil on days 1-5 and 75 mg/m(2) cisplatin on day 8 and simultaneous
      radiation (40 Gy), and a second course starting on day 36, followed by surgery.
      Abdomino-thoracic oesophagectomy and systematic 2-field lymphadenectomy were
      performed in patients with Barrett's carcinoma. D2-gastrectomy was performed in
      patients with type 2 or 3 cancer of the oesophagogastric junction according to
      the Siewert classification. Probability of survival was estimated using the
      Kaplan-Meier method. RESULTS: 16 patients with a mean age of 57 years were
      enrolled in this study. Surgery was performed in 14 of these patients. Response
      to treatment was evident in 10 patients, but none of these patients had complete
      histopathologic response. Toxicity related to radiochemotherapy was mild to
      moderate (37.5%). Perioperative complications, both medical and surgical,
      occurred in 71.4% of patients. 2 patients had fatal complications. 30-day
      mortality was 25.4%. The probability of survival at 2 years after surgery was
      61.2%. CONCLUSION: Neoadjuvant radio-chemotherapy followed by surgery for cancer
      of the oesophagogastric junction is associated with a considerable rate of
      complications. Histopathologic response to radio-chemotherapy is poor. In
      consequence of these preliminary results, the present study was terminated and
      the protocol of a future study was modified.

PMID- 11455223
TI  - Dose reduction of steroid premedication for paclitaxel: no increase of
      hypersensitivity reactions.
AB  - BACKGROUND: Premedication with dexamethasone, ranitidine and clemastine is
      mandatory for patients receiving paclitaxel to avoid hypersensitivity reactions.
      The proposed dexamethasone dose is 20 mg orally 12 and 6 h prior to paclitaxel
      infusion. With this premedication severe hypersensitivity reactions are reduced
      to 1-2% of the treated patients. Besides this oral schedule a single dose of
      dexamethasone, 40 mg given i.v., just prior to paclitaxel has been shown to be
      equally effective. In an attempt to reduce steroid-induced side effects,
      especially for patients receiving weekly paclitaxel protocols, we reduced the
      dexamethasone dose. PATIENTS AND METHODS: A total of 132 patients were treated on
      an outpatient basis with paclitaxel-containing protocols. Paclitaxel was given in
      doses of 135-175 mg/m(2) once every 3 weeks in 76 patients and/or with 100
      mg/m(2) weekly in 70 patients. Dexamethasone premedication was given in a single
      dose (40, 20, 10 mg) as an infusion directly before paclitaxel. RESULTS: 0/46
      patients receiving 40 mg dexamethasone premedication in 235 cycles and 0/48
      patients receiving 20 mg dexamethasone premedication in 186 cycles experienced a
      severe hypersensitivity reaction. 1/52 patients receiving 10 mg dexamethasone in
      480 applications developed a severe hypersensitivity reaction with bronchospasm,
      hypotension and supraventricular tachycardia shortly after her first paclitaxel
      infusion started. CONCLUSION: No increase of severe hypersensitivity reactions is
      seen when dexamethasone premedication is reduced to doses of 20 or even 10 mg
      prior to paclitaxel infusion.

PMID- 11455224
TI  - Androblastoma of the ovary: clinical, diagnostic and histopathologic features.
AB  - Androblastomas of Sertoli-Leydig cell tumors of the ovaries are classified into
      the group of sex cord stromal tumors and represent an extremely rare form of
      tumor (0.2% of all ovarian tumors) in women. Their malignant potential is lower
      than that of epithelial ovarian cancer. They cause signs of virilization,
      although these are not obligatory. In many cases secondary amenorrhea is the only
      symptom of the disease. This leads to an intensive search for the source of the
      disorder. Frequently only the elevated production of androgens gives a
      preoperative clue to the tumor type. The recommendation to include the
      measurement of androgen levels in the routine diagnosis of secondary amenorrhea
      must therefore be endorsed. The tumors are usually sonographically identifiable;
      in differential diagnosis, hyperandrogenemia of other origins (e.g., Cushing's
      disease, adrenal hyperplasia, pituitary adenoma, other causes of ovarian and
      adrenal androgen hypersecretion, intersexuality, medically induced
      androgenization) have to be ruled out. In view of the good prognosis, the therapy
      of choice consists simply in adnexectomy of the affected side. With regular
      measurement of serum androgen levels an effective control of the course of the
      disorder is possible. A conclusive pathological diagnosis is difficult as
      heterologous tumors and mixed tumors exist and, furthermore, other tumor types
      are capable of imitating Sertoli-Leydig cell tumors.

PMID- 11455225
TI  - Which factors render cost-covering lump-sum charging difficult for the treatment
      of patients with acute leukemias?
AB  - BACKGROUND: Growing budget limitations and the planned charging subject to
      Diagnosis-Related Groups (DRG) points raise the question as to what costs are
      incurred by the induction therapy and early consolidation treatment of patients
      with acute myeloid leukemias (AML) and whether these can be compensated in a cost
      covering manner by a system based on DRG points. PATIENTS AND METHODS: For 100
      patients recruited within the framework of the "Kooperative AML-Studie 96" of the
      Suddeutsche Hamoblastosegruppe a process cost analysis was made between 1996 and
      1999. All manpower and material costs incurred in the department itself and in
      the secondary services departments as well as the basic cost shares were recorded
      taking into due account the length of stay. The cost breakdown was effected based
      on a double induction therapy and one early consolidation treatment. RESULTS: It
      turns out that substantial differences exist between lower und upper limits of
      the length of stay and costs. For all three therapy blocks for patients up to 60
      years the cost spread varies between 63 and 204 kDM with a median of 105 kDM, and
      for older patients between 55.6 and 146.6 kDM with a median of 87.6 kDM. On
      average, the costs subject to length of stay were roughly 70%. CONCLUSIONS: As
      the costs per case are subject to a spread and, for this relatively small group
      of patients, are extremely high, the fixing of a case-related lump sum is
      problematic, the more so as age of patient, comorbidity, type of therapy, ist
      outcome, and therapy-induced complications represent decisive influencing
      factors.

PMID- 11455226
TI  - [Clinical radiotherapy in the 19th and 20th century: history and perspective].

PMID- 11455227
TI  - Screening for ventricular shunt function in children with hydrocephalus secondary
      to meningomyelocele.
AB  - OBJECTIVE: To evaluate the current method of using computerized tomographic (CT)
      scans to screen for ventricular shunt failure in children who have hydrocephalus.
      DESIGN: Retrospective review of 112 randomly selected charts. PATIENTS: Children
      diagnosed with infantile hydrocephalus secondary to meningomyelocele, who were
      treated at the Andrew J. Kirch Developmental Services Center since 1978. RESULTS:
      One hundred and twelve patients were monitored with CT scans for an average of
      12.2 years. There was a total of 2,869 CT scans and an average of 2.1 CT scans
      per year. Shunt failure was diagnosed 76% of the time by symptoms, 15% by
      physical findings and 8% by routine CT scans. Sixteen patients had no shunt
      failure, whereas the remaining 96 had 255 shunt failures. Complications occurred
      during 30 of the 255 admissions. One child died due to complications directly
      related to shunt failure. No statistically significant correlations were found
      between the length of stay or complications and method of diagnosis. CONCLUSIONS:
      Although children in this study received frequent CT scans, 76% of the episodes
      of shunt failure were diagnosed because of symptoms. Children admitted to the
      hospital with symptomatic shunt failure did not have more complications or a
      longer stay than those diagnosed by routine CT scan. This study suggests that the
      use of routine CT scans to diagnose shunt failure while patients are asymptomatic
      does not lead to significantly better medical outcomes and is not cost-effective.
      However, before routine CT scans are eliminated, a prospective study needs to be
      conducted that examines outcomes such as cognitive and psychological functioning.

PMID- 11455228
TI  - Image-guided, frameless stereotactic sectioning of the corpus callosum in
      children with intractable epilepsy.
AB  - Corpus callosotomy is an effective neurosurgical procedure for children with
      intractable atonic or drop attack seizures. While this procedure has not changed
      significantly over the past three decades, some technical issues remain to be
      resolved. These include the intraoperative determination of the extent of the
      callosotomy, the need to stage the procedure, as well as side of approach of
      craniotomy. We report our 8-year experience with corpus callosotomy using a
      frameless stereotactic image-guided system (ISG Viewing Wand). Seventeen children
      with atonic seizures underwent sectioning of the corpus callosum. The mean
      patient age was 10.5 years. Six children underwent complete callosotomy while 11
      underwent resection of the anterior two-thirds. MRI 3D reconstruction of the
      sagittal sinus and draining cerebral veins was undertaken in all cases. The side
      of the craniotomy was determined on the basis of favorability of the draining
      veins with respect to the extent of the callosotomy. The extent of the
      callosotomy was determined by intraoperative feedback using the ISG Viewing
      Wand((R)). Nine of 11 patients in the partial callosotomy group and 4 of 6
      patients in the complete callosotomy group showed significant improvement in
      atonic seizures. We conclude that the use of frameless stereotaxy can function as
      an important adjunct in the planning and conduction of successful sectioning of
      the corpus callosum in children with intractable seizures.

PMID- 11455229
TI  - Intra-operative MRI-guided approaches to the pediatric posterior fossa tumors.
AB  - INTRODUCTION: The posterior fossa in a child poses a considerable challenge to
      the neurosurgeon. MRI-guided surgery allows for real time interaction between
      imaging and the neurosurgeon, not permitted by frameless stereotaxy, and with
      higher resolution than ultrasound or CT. MATERIALS AND METHODS: The University of
      Minnesota 1.5 T Phillips interventional MRI was used. From 1997 to 2000, nine
      posterior fossa intraoperative magnet cases out of eleven were pediatric. The
      mean age was 6.4 years and the median age 7. Seven midline craniotomies were
      performed, of which three were re-operations. Two were burr hole placements, one
      for cyst aspiration and P32 instillation, and the other for tumor biopsy.
      RESULTS: Two tumors were predominantly in the fourth ventricle, four in the
      cerebellum, two in the brainstem, and one in the prepontine cystern. Four tumors
      were juvenile pilocytic astrocytomas, two were anaplastic astrocytomas, and one
      each was ependymoma, craniopharyngioma cyst, and medulloblastoma. Four patients
      had complete radiologic resection. Two had maximal resections limited by vital
      structures. P32 instillation and tumor biopsy were done in a single pass. Follow
      up ranged from 3 months to 1.4 years. The cyst that was aspirated and had P32
      instillation remains absent. The two mortalities were in the patients with
      medulloblastoma and anaplastic astrocytoma. There were no intra-operative
      mortalities. The other patient with anaplastic astrocytoma progressed. The
      remainder had stable imaging. CONCLUSION: MRI-guided surgery results in improved
      resection imaging and real-time needle guidance in tumor operations. Its value
      could lie in low-grade lesions, where maximal resection is most beneficial.

PMID- 11455230
TI  - Oligodendroglial ganglioglioma with anaplastic features arising from the
      thalamus.
AB  - Anaplastic gangliogliomas with an oligodendroglial component are exceedingly rare
      tumors of uncertain growth potential. We report a 17-year-old female with a
      massive ganglioglioma containing anaplastic oligodendroglioma apparently arising
      from the thalamus. Two weeks after partial resection, she was started on a
      regimen including escalated doses of topotecan in combination with a fixed-dosage
      intensification regimen of cisplatin, cyclophosphamide and vincristine with
      subsequent hyperfractionated external beam radiotherapy. She currently has stable
      disease.

PMID- 11455231
TI  - Giant ependymal cyst of the temporal horn -- an unusual presentation. Case report
      with review of the literature.
AB  - Primary benign cystic lesions in the brain are uncommon. However, extracerebral
      cysts like arachnoid cyst, epidermoid cyst and craniopharyngiomas are fairly
      common lesions. Also, colloid cyst in the third ventricle, dermoid cyst and
      endodermal cyst in the extracerebral location are not uncommon. On the contrary,
      intraventricular ependymal and choroidal cysts in the intraventricular location
      are infrequent. Surgical intervention is warranted in cysts, which produce a mass
      effect and raised intracranial pressure. We present an interesting case of a
      giant intraventricular ependymal cyst in the temporal horn in a 14-year-old boy,
      who presented with recent onset of headaches and epilepsy. He also had long
      standing progressive proptosis of the left eye and left temporal bossing.
      Excision of this cystic lesion was curative. Interesting clinical and
      neuroimaging features are presented.

PMID- 11455232
TI  - Lobar and multilobar resections for medically intractable pediatric epilepsy.
AB  - Pediatric epilepsy surgery patients are different than adult epilepsy surgery
      patients by having a higher proportion of extratemporal than temporal lobe
      lesions, and by having cortical dysplasia as the most frequent pathology. We
      analyzed 111 pediatric epilepsy patients who received lobar or multilobar
      resections at the University of California, Los Angeles, between the years 1986
      and 2000 to determine if there were differences in seizure outcome by lobe of
      resection and tissue pathology. Results showed that temporal lobe resection
      patients had lower pre- and postoperative seizure frequencies compared with
      extratemporal single lobe resection patients (p < 0.05). Furthermore, single lobe
      resection patients from any brain region had lower pre- and postoperative seizure
      frequencies compared with multilobar resection patients (p < 0.05), an effect
      which was due to the better seizure outcomes in temporal lobe resection cases.
      Patients with mass lesions had the best postoperative seizure control, followed
      by cortical dysplasia patients and other pathologies (p < 0.05). In all patient
      groups, there was a significant reduction in pre- to postoperative seizure
      frequencies (p < 0.0001). These results indicate that postsurgery seizure
      outcomes in pediatric epilepsy surgery patients vary by lesion location and
      pathology, with the best outcomes in temporal lobe patients with mass lesions.
      However, surgical resections of epileptogenic lesions, regardless of lobe, were
      associated with significant postoperative improvements in seizure frequency.

PMID- 11455233
TI  - A 4-year-old boy with partial complex seizures.

PMID- 11455234
TI  - Diffusion-weighted magnetic resonance image of a pediatric spinal epidermoid
      cyst.

PMID- 11455235
TI  - Safety and efficacy of remifentanil infusion in craniosynostosis repair in
      infants.

PMID- 11455236
TI  - Congratulations! the american journal of geriatric cardiology has been accepted
      for indexing in index medicus!

PMID- 11455237
TI  - Outpatient cardiac infusion units: impact in elderly patients with refractory
      heart failure.
AB  - BACKGROUND: The use of intermittent intravenous infusions of inotropic drugs is
      under evaluation in the management of patients with refractory heart failure.
      OBJECTIVES: We investigated the impact of intermittent outpatient infusions of
      inotropes on hospital admissions, emergency room visits, functional class, and
      symptom-free interval after administration of inotropes to elderly patients with
      advanced heart failure symptoms. METHODS: This retrospective analysis involved 24
      elderly outpatients with a New York Heart Association class of III or IV and
      refractory heart failure symptoms. RESULTS: Seven patients with class III heart
      failure (age 74A+/-4 years; left ventricular ejection fraction 27A+/-9%) and 17
      patients of class IV (age 73A+/-4 years; LVEF 21A+/-10%) were included. Twenty
      patients were males. A total of 365 outpatient treatment sessions were
      administered, with 15A+/-9 sessions per patient (range, 6-43). Eleven patients
      improved and were discharged; seven patients died; three discontinued treatment;
      two patients remain on therapy; and one patient required continuous infusion.
      During this treatment, there were only three emergency room visits and six
      hospital admissions due solely to heart failure. Fourteen patients required no
      emergency room visits or hospitalization. Of the patients discharged from the
      program, the interval without heart failure symptoms ranged from 60-356 days,
      with an improvement in NYHA class from 3.5A+/-0.6 to 1.4A+/-0.5 and no emergency
      room visits or hospital admissions. CONCLUSIONS: This type of therapy is well
      tolerated among elderly patients with refractory heart failure symptoms and its
      use deserves further investigation.

PMID- 11455238
TI  - Multifocal atrial tachycardia and Ibutilide.
AB  - Multifocal atrial tachycardia is an electrocardiographic phenomenon seen
      primarily in the elderly. The hemodynamic consequences of multifocal atrial
      tachycardia in an elderly woman are presented. Successful treatment with
      Ibutilide is demonstrated. Treatment with a class III antiarrhythmic agent
      opposes the frequently accepted mechanism of triggered activity in causing this
      arrhythmia.

PMID- 11455239
TI  - Mitral annulus calcification with a mobile component as a possible source of
      embolism.
AB  - Mitral annulus calcification has been associated with embolic events, but the
      precise pathophysiology has not been elucidated. The authors describe four
      patients who experienced embolic events whose transesophageal echocardiograms
      showed a mitral annulus calcification, with a mobile component that exhibited the
      same echogenicity as the calcification. Three patients had no other conditions
      known to be associated with embolism. On follow-up transesophageal
      echocardiography, the mobile component of the mitral annulus calcification had
      disappeared in three patients. These findings support the hypothesis that mitral
      annulus calcification not only is associated with but also is possibly a direct
      cause of embolic events in some patients.

PMID- 11455240
TI  - Updated review of the coronary artery bypass grafting option in octogenarians:
      good tidings.
AB  - This review of the literature is presented in an attempt to keep pace with the
      constantly changing statistics in postsurgical outcomes, which reflect the
      considerable strides in technology and technical skills that have been made
      during the past decade in cardiovascular surgery. Although there is still much to
      be done in terms of improving surgical techniques and managing emergency cases,
      the reported results of coronary artery bypass grafting in octogenarians are
      similar to or even better than those obtained with medical or angioplastic
      approaches, and the life expectancy and quality of life are similar to or better
      than those of age-matched controls.

PMID- 11455241
TI  - Database Conference January 27-30, 2000, Washington D.C.--Do existing databases
      answer clinical questions about geriatric cardiovascular disease and stroke?
AB  - EXECUTIVE SUMMARY: Most randomized, controlled trials evaluating the
      effectiveness of pharmaceutical, surgical, and device interventions for the
      prevention and treatment of cardiovascular disease have excluded patients over 75
      years of age. Consequently, the use of these therapies in the older population is
      based on extrapolation of safety and effectiveness data obtained from younger
      patients. However, there are many registries and observational databases that
      contain large amounts of data on patients 75 years of age and older, as well as
      on younger patients. Although conclusions from such data are limited, it is
      possible to define the characteristics of patients who did well and those who did
      poorly. The goal of this conference was to convene the principal investigators of
      these databases, and others in the field of geriatric cardiology, to address
      questions relating to the safety and effectiveness of treatment interventions for
      several cardiovascular conditions in the elderly. Seven committees discussed the
      following topics: (I) Risk Factor Modification in the Elderly; (II) Chronic Heart
      Failure; (III) Chronic Coronary Artery Disease: Role of Revascularization; (IV)
      Acute Myocardial Infarction; (V) Valve Surgery in the Elderly; (VI)
      Electrophysiology, Pacemaker, and Automatic Internal Cardioverter Defibrillators
      Databases; (VII) Carotid Endarterectomy in the Elderly. The chairs of these
      committees were asked to invite principal investigators of key databases in each
      of these areas to discuss and prepare a written statement concerning the
      available safety and efficacy data regarding interventions for these conditions
      and to identify and prioritize areas for future study. The ultimate goal is to
      stimulate further collaborative outcomes research in the elderly so as to place
      the treatment of cardiovascular disease on a more scientific basis.

PMID- 11455242
TI  - Ethical Issues in the management of geriatric cardiac patients--after the death
      of his appointed surrogate, a demented, senile patient is caught in a whirlwind
      of medical decision-making.

PMID- 11455243
TI  - Saccular aortic arch aneurysm with laminated thrombus.

PMID- 11455244
TI  - Misleading lead II "rhythm strip".

PMID- 11455245
TI  - Hearts 90 years of age or older.

PMID- 11455246
TI  - Evidence of T cell clonality in the infectious tolerance pathway: implications
      toward identification of regulatory T cells.
AB  - We have shown that a rare population of regulatory CD4+ T cells plays a key role
      in the acquisition of infectious tolerance in rat sensitized recipients of
      cardiac allografts pretreated with nondepleting anti-CD4 mAb. This study was
      designed to analyze the TCR Vbeta expression patterns in this transplantation
      model. First, we used Vbeta-specific RT-PCR to show that there was no
      differential usage of TCR Vbeta genes by T cells mediating rejection or
      tolerance. Indeed, graft-infiltrating lymphocytes expressed most of the 22 known
      rat TCR Vbeta genes in both recipient groups, suggesting unrestricted TCR Vbeta
      repertoire in alloreactive T cells. Then, we applied CDR3 spectrotyping of TCR
      beta-chain to assess the clonality of T cells at different anatomic sites. CDR3
      size restriction, indicative of the presence of T cell clones, was observed in
      graft-infiltrating lymphocytes but not in draining lymph nodes or spleen of
      tolerant hosts. Consisent with the clonal expansion, T cells in tolerated grafts
      exhibited the memory phenotype at a much higher percentage as compared with
      peripheral lymphoid organs. Moreover, in tolerated graft-infiltrating
      lymphocytes, the CD3 size restriction occurred in limited Vbeta gene families,
      with Vbeta8.1 and Vbeta18 most frequently detected. Hence, T cells at the graft
      site of tolerant recipients contain T cell clones expressing selective Vbeta
      genes. This phenotypic characteristics of the tolerogenic GILs may potentially be
      used as a novel marker to identify operational regulatory T cells in organ
      allograft recipients.

PMID- 11455247
TI  - Novel approaches toward early diagnosis of islet allograft rejection.
AB  - BACKGROUND: The inability to diagnose early rejection of an islet allograft has
      previously proved to be a major impediment to progress in clinical islet
      transplantation. The need to detect early rejection will become even more
      relevant as new tolerance-inducing protocols are evaluated in the clinic. We
      explored three novel approaches toward development of early diagnostic markers of
      islet rejection after islet allotransplantation. METHODS: (a) Canine islet
      allograft transplant recipients were immunosuppressed for 1 month, then therapy
      was withdrawn. Serum glutamic acid decarboxylase antigen (GAD65), an endogenous
      islet protein, was monitored daily with a CO2 release assay. (b) Rodent islets
      were genetically engineered to express a unique foreign protein (beta
      galactosidase) by using adenoviral vectors, and after allograft transplantation,
      the viral-specific protein was measured in serum using optical luminescence. (c)
      Rodents receiving islet allografts were immunosuppressed temporarily, and daily
      glucose tolerance tests were followed until graft failure occurred. RESULTS: (a)
      Although serum monitoring of GAD65 antigen demonstrated elevated levels preceding
      loss of graft function in preliminary studies, the effect was not reproducible in
      all animals. (b) Genetically engineered rodent islets demonstrated normal insulin
      kinetics in vitro (insulin stimulation index 2.57+/-0.2 vs. 2.95+/-0.3 for
      control islets, P=ns), and purified viral protein products had a stable half-life
      of 8 hr in vivo. After islet allotransplantation, there were two peak elevations
      in serum viral proteins, confirming that an intra-islet "sentinel signal" could
      be detected serologically during acute rejection. There was no lead-time ahead of
      hyperglycemia, however. (c) Daily sequential intravenous glucose tolerance (IVGT)
      tests demonstrated evidence of allograft dysfunction (decline in KG) with a 2-day
      lead time to hyperglycemia (2.58+/-0.3 vs. 1.63+/-0.2%/min, respectively,
      P<0.001), with an accuracy of 89%, sensitivity of 78%, and specificity of 95%.
      CONCLUSIONS: Of the three diagnostic tests, metabolic assessment with an
      abbreviated IVGT was the most effective method of demonstrating early islet
      dysfunction due to rejection.

PMID- 11455248
TI  - Apoptosis and rejection in rat intestinal transplantation: correlation with FK506
      doses and donor specific bone marrow infusions.
AB  - BACKGROUND: Our purpose was to investigate the occurrence and the evolution of
      apoptosis of enterocytes during acute and chronic rejection in an experimental
      model of allogeneic heterotopic small bowel transplantation (SBTx). METHODS:
      Forty-five rats were divided in 10 experimental groups according to the dose of
      FK506 administration and donor bone marrow infusions (DBMI). Groups 1 and 2 did
      not received BMI. Groups 3 and 4 received 150x106 cells at day 0, groups 5 and 6
      received 75x106 cells at days 0-4, groups 7 and 8 received 75x106 cells at days 4
      and 10, and groups 9 and 10 received 30x106 cells at days 4, 10, 15, 20, and 25.
      Animals of groups 1, 3, 5, 7, and 9 were immunosuppressed with 0.5 mg/kg FK 506,
      although the remaining groups with 1 mg/kg FK 506, from day 0 to 4 after
      transplant. Fragment end labeling of DNA was used to detect apoptosis. RESULTS:
      The number of apoptotic cells detected was highest at day 15 (184+/-154) and then
      progressively decreased thereafter (day 30=159+/-197; day 45=80+/-167; day 60=0).
      The number of apoptotic enterocytes was found increased during mild (151+/-108)
      and moderate (281+/-161) allograft rejection, although a low apoptotic rate was
      observed in cases without rejection (59+/-13) and during severe (53+/-131) and
      chronic rejection (46+/-136). Furthermore the number of labeled cells was found
      inversely correlated with fibrosis (P<0.0001). There was no correlation between
      apoptosis and the presence or absence of DBMI; however, at day 15 rats receiving
      1 mg/day of FK 506 had a significantly lower number of apoptotic cells detected
      (127+/-103 vs. 233+/-174; P<0.02). CONCLUSIONS: In this study the number of
      apoptotic cells correlated positively with mild and moderate rejection episodes.
      In case of severe and chronic rejection a low apoptotic rate was found due
      probably to extensive necrosis and fibrosis of the mucosa. These data suggest an
      important role of apoptosis in acute and chronic intestinal rejection in a rat
      model of intestinal transplantation. Determination of apoptosis in allografts
      might represent an early sign of small bowel rejection and a useful marker in
      defining the degree of rejection and its outcome/prognosis.

PMID- 11455249
TI  - A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed
      by injection of donor bone marrow cells via portal vein.
AB  - A new strategy for organ allografts that does not require recourse to
      immunosuppressants is established in mice. The strategy includes sublethal (7 Gy)
      irradiation followed by the injection of donor bone marrow cells (BMCs) via the
      portal vein (P.V.) and organ allografts 1 day after irradiation. Irradiation
      doses (< or =7 Gy) are found to allow the recipients to survive without the need
      to reconstitute the BMCs, as the recipient hematolymphoid cells can gradually
      recover. One hundred percent of recipients irradiated with 7 Gy followed by
      either P.V. or i.v. injection of donor BMCs accept organ allografts (the skin,
      pancreas, and adrenal glands) for more than 1 year. However, organ allograft
      survival rates decrease when irradiation doses are reduced; the skin graft
      survival rate of mice treated with 6.5 Gy and P.V. injection of BMCs is 79%,
      whereas that of mice treated with 6.5 Gy and i.v. injection is 50%, indicating
      that the P.V. injection of BMCs induces persistent tolerance more effectively
      than the i.v. injection. H-2 typing reveals that almost all the hematolymphoid
      cells (>98%) in the peripheral blood and hematolymphoid organs are donor-derived
      even 1 year after the treatment (7 Gy and P.V.). The T cells are tolerant to both
      donor-type and host-type MHC determinants. The major mechanism underlying the
      persistent tolerance induced by this strategy seems to be because of clonal
      deletion. This simple and safe strategy would be of great advantage for human
      organ transplantation.

PMID- 11455250
TI  - Comparative evaluation of Celsior solution versus Viaspan in a pig liver
      transplantation model.
AB  - BACKGROUND: In a pig liver transplantation model, we compared the effects of
      Celsior solution (CS), an extracellular preservation solution, with Viaspan
      (University of Wisconsin solution, UW) on graft function and animal survival.
      METHODS: Pig livers were flushed with either CS or UW solution and cold-stored
      for 12 hr (group 1) or for 8 to 10 hr (group 2). Grafts were transplanted
      orthotopically. Intrahepatic reduced and oxidized glutathione and adenine
      nucleotides were evaluated 1 hr after reperfusion. Liver function of transplanted
      animals was monitored for up to 6 days by serum transaminases, total bilirubin,
      purine nucleoside phosphorylase, and prothrombin levels. RESULTS: In group 1, all
      animals died within 24 hr after reperfusion regardless of the preservation
      solution used. In group 2, no significant difference was seen in survival between
      the CS (72%) and the UW (67%) groups 6 days after transplantation, and there were
      no statistically significant differences in the biochemical data. There were no
      differences in histological evaluation of the livers at the time of death or
      killing of the animals between the CS and UW groups. CONCLUSION: Within the
      limits of this pilot study, CS is equivalent to UW in terms of graft function and
      animal survival.

PMID- 11455251
TI  - Differentiation of transplanted bone marrow cells in the adult mouse brain.
AB  - BACKGROUND: Bone marrow transplantation is reportedly effective in preventing the
      progression of neurological deterioration in lysosomal storage disorders,
      although the mechanism underlying the therapeutic effects remains to be
      elucidated. Recent research on stem cell biology suggests that bone marrow cells
      contain nonhematopoietic stem cells, including brain precursor cells. To evaluate
      the contribution of bone marrow cells as carriers for cell and gene therapy of
      neurological disorders, we studied the fate of transplanted bone marrow cells in
      the adult mouse brain. METHODS: Bone marrow cells were genetically marked with a
      retroviral vector containing the green fluorescence protein gene and then
      transplanted into irradiated mice by either systemic infusion or direct
      injection. To identify cell types, brain sections were stained with specific
      antibodies against neuronal cell markers-neuron specific enolase for neurons,
      glial fibrillary acidic protein (GFAP) for astrocytes, carbonic anhydrase II
      (CAII) for oligodendrocytes, and ionized calcium binding adaptor molecule 1
      (Iba1) for microglia-and then examined under a confocal microscope. RESULTS:
      Twenty-four weeks after systemic infusion, transplanted cells expressed Iba1 but
      none of the other brain cell markers. Conversely, 12 weeks after direct
      injection, transplanted cells were stained with antibodies against GFAP, CAII,
      and Iba1. CONCLUSIONS: Bone marrow contains cells capable of differentiating into
      oligodendrocytes, astrocytes, and microglia when exposed to the brain
      microenvironment. Autologous bone marrow cells may be useful as carriers for ex
      vivo gene therapy for lysosomal disorders with neurological symptoms.

PMID- 11455252
TI  - Mast cells in acute and chronic rejection of rat cardiac allografts--a major
      source of basic fibroblast growth factor.
AB  - BACKGROUND: Studies of cardiac allograft arteriosclerosis, i.e., chronic
      rejection, have largely focused on mononuclear inflammatory cell infiltrates in
      the vascular wall and periphery of the occluded vessels. The purpose of this
      study was to investigate the role of mast cells in the development of acute and
      chronic rejection in rat cardiac allografts. METHODS: In the acute rejection
      model, transplant recipients were not treated with immunosuppressants, and the
      grafts were removed 5 days after transplantation at the time of severe acute
      rejection. In the chronic rejection model, the recipients were administered
      triple-drug immunosuppression, and the grafts were removed 90 days after
      transplantation. RESULTS: During acute rejection, the number of mast cells was
      not increased, but the localization pattern differed from that of syngeneic
      grafts. In acute rejection, mast cells were located in the perivascular region of
      the allografts, but in syngeneic grafts, mast cells had a more interstitial
      location. In the chronic rejection model, the cardiac allografts with severe
      intimal thickening showed large numbers of mast cells at perivascular sites of
      occluded intramyocardial vessels and in the interstitium. Linear regression
      analysis revealed a significant correlation between the numbers of perivascular
      and interstitial mast cells and the intensity of intimal thickening. The majority
      of mast cells showed positive immunoreactivity to basic fibroblast growth factor
      (bFGF). Macrophage bFGF expression was not so prominent, but macrophages were
      more frequent in numbers. Tumor necrosis factor-alpha expression was detected
      mainly in macrophages and in only a few mast cells. When the intensity of
      arteriosclerosis was decreased by an increase in the intensity of
      immunosuppression, the numbers of intragraft mast cells and other mononuclear
      cells, and also the production of their respective cytokines, bFGF and tumor
      necrosis factor-alpha, gradually diminished. CONCLUSIONS: Taken together, our
      data show that the intensity of intramyocardial mast cell infiltration was
      associated with the intensity of chronic inflammation and allograft
      arteriosclerotic changes, but not with acute rejection, and that mast cells, in
      addition to macrophages, are a major source of myocardial bFGF. The results also
      demonstrate that when the T-cell activation pathway is blocked using cyclosporin,
      the number of mast cells is decreased. Cyclosporin may have affected the cytokine
      production that interfered with both the mast cell-dependent initiation and the
      leukocyte- and mast cell-dependent amplification and progression of the immune
      responses influenced by mast cell-leukocyte cytokine cascades. bFGF produced by
      mast cells may contribute to enhanced inflammation, neovascularization, and
      fibrosis during cardiac allograft arteriosclerosis.

PMID- 11455253
TI  - Hyperhomocysteinemia in stable pediatric, adolescents, and young adult renal
      transplant recipients.
AB  - BACKGROUND: High total plasma homocysteine (tHcy) levels are accompanied by an
      increased risk for premature development of atherosclerosis and atherothrombosis.
      Adult renal transplant recipients have elevated tHcy levels. Corresponding data
      in pediatric, adolescent, and young adult renal transplant recipients are scarce.
      We investigated whether tHcy levels were elevated in stable renal transplant
      recipients who received kidney grafts before age 18. METHODS: This cross
      sectional study was conducted during routine posttransplantation follow-up.
      Fasting tHcy levels, serum creatinine, and lipoprotein profile were measured in
      38 clinically stable renal transplant recipients with different degrees of renal
      function. No patient was receiving B vitamin or folic acid supplementation.
      Estimated glomerular filtration rate (GFR) was assessed according to Schwartz's
      formula. All patients followed a triple-drug immunosuppressive regimen, with the
      exception of three patients (deflazacort and azathioprine). Forty-one apparently
      healthy subjects constituted the control group. tHcy levels were determined by
      fluorescence polarization immunoassay in an IMx analyzer. RESULTS: Mean tHcy
      levels in transplant recipients were significantly higher than in controls
      (16.8+/-8.7 micromol/L and 9.5+/-2.3 micromol/L, respectively; P<0.01). A
      significant positive correlation between tHcy and serum creatinine levels was
      observed for both transplant recipients (rS=0.70, P<0.01) and controls (rS=0.54,
      P<0.01). In transplant recipients, tHcy correlated negatively with estimated GFR
      (rS=[minus]0.47, P<0.05). Fasting tHcy levels in excess of 14.6 micromol/L (>95th
      percentile in controls) were present in 19 (50%) patients; 14 of these patients
      had an estimated GFR<60 ml/min per 1.73 m2. When the renal transplant recipients
      were analyzed by renal function, mean tHcy was significantly higher in patients
      with an estimated GFR<60 ml/min per 1.73 m2 compared with patients with an
      estimated GFR> or =60 ml/min per 1.73 m2 (20.5+/-9.9 vs. 13.2+/-5.8 micromol/L,
      P<0.01). Both groups were significantly different from controls (P<0.01). No
      relationship was found between tHcy level and either cumulative cyclosporine or
      cumulative methylprednisone doses. No differences were observed in tHcy levels or
      lipoprotein profile between patients who were receiving deflazacort and those on
      methylprednisone. CONCLUSIONS: Hyperhomocysteinemia in renal transplant
      recipients is a common condition. Testing for fasting tHcy level might be a
      useful tool to identify patients at increased risk for development of vascular
      disease.

PMID- 11455254
TI  - Excess risk of renal allograft loss associated with cigarette smoking.
AB  - BACKGROUND: Cigarette smoking contributes to a number of health-related problems,
      but its impact on renal transplant survival beyond accelerated patient death is
      unclear. METHODS: We performed a cohort study of 645 adult renal allograft
      recipients from 1985 to 1995 to evaluate the relationship between smoking and
      graft outcome. RESULTS: Twenty-four percent of recipients (156/645) were smokers
      at the time of transplant evaluation. Of these, 90% continued to smoke after
      transplantation. Pretransplant smoking was significantly associated with reduced
      overall graft and death-censored graft survival. Patients who were smokers at the
      time of pretransplant evaluation had kidney graft survival of 84%, 65%, and 48%
      at 1, 5, and 10 years, respectively, compared with graft survival in nonsmokers
      of 88%, 78%, and 62% (P=0.007). Pretransplant smoking adversely affected death
      censored graft survival in recipients of cadaveric (P=0.02) and of living donor
      kidneys (P=0.02). Reduced graft survival in pretransplant smokers could not be
      accounted for by differences in rejection (64% vs. 61%, P=0.35). In a
      multivariate analysis, pretransplant smoking was associated with a relative risk
      of 2.3 for graft loss. Among patients with a smoking history before
      transplantation, death-censored graft survival was significantly higher for those
      who quit smoking before transplant evaluation. CONCLUSIONS: Cigarette smoking
      before kidney transplantation contributes significantly to allograft loss. The
      effect of smoking on graft outcome is not explained by increases in rejection or
      patient death. Smoking cessation before renal transplantation has beneficial
      effects on graft survival. These effects should be emphasized to patients with
      end-stage renal disease who are considering renal transplantation.

PMID- 11455256
TI  - The impact of donor age on liver transplantation: influence of donor age on early
      liver function and on subsequent patient and graft survival.
AB  - BACKGROUND: The urgent need to increase the organ donor pool has led to the
      expansion of criteria for donor selection. The aim of this study was to analyze
      the influence of donor age on early graft function, subsequent graft loss, and
      mortality after liver transplantation (LT). METHODS: Data on LT were evaluated
      retrospectively in a population-based cohort of 400 LTs in 348 patients. Of
      these, 21 (5%) were from donors >70 years old. Pretransplantation donor and
      recipient characteristics and the evolution of recipients were analyzed. The
      influence of donor age as a risk factor was assessed using univariate and
      multivariate analyses. RESULTS: Actuarial graft survival was 89% at 1 month after
      LT, 81% after 6 months, and 59% after 60 months. Multivariate analysis
      demonstrated that only donor age (>70 years old) was associated with a higher
      risk of long-term graft loss (relative risk [RR]=1.4, 95% confidence interval
      [CI]=1-1.9; P=0.03) and mortality (RR=1.7, 95% CI=1.2-2.3; P=0.01). Graft
      survival of septuagenarian livers was 80% at 1 month after LT, 56% after 6
      months, and 25% after 54 months. Actuarial survival analysis (Kaplan-Meier
      curves) also demonstrated worse evolution in recipients of livers from old donors
      (log-rank test, P<0.001). CONCLUSIONS: Advanced donor age is associated with
      lower graft and recipient survival.

PMID- 11455255
TI  - Alteration of collagen IV in acutely deteriorated renal allografts.
AB  - BACKGROUND: The changes in the basement membrane occurring in acutely
      deteriorated renal allografts (ADR) have not been extensively investigated. Our
      purpose is to elucidate the alteration of collagen IV, a main constituent of the
      basement membrane in ADR. METHODS: Fifty biopsy specimens of ADR and 10 of
      chronic transplant nephropathy (CTN) were examined with two monoclonal antibodies
      specific for collagen IV. JK199 and JK132 are monoclonal antibodies that
      recognize triple helical collagen IV containing the alpha1 chain. JK199
      recognizes all the basement membrane containing [alpha1 (IV)]2alpha2(IV),
      although JK132 reacts only with a limited portion of it. In the normal kidney,
      JK199 reacts with the mesangial matrix, the basement membrane of Bowman's capsule
      (BBM), and the tubular basement membrane, as well as with the glomelular basement
      membrane (GBM). JK132 reacts with the mesangial matrix, BBM, and the tubular
      basement membrane. RESULTS: In ADR, increased intensity of JK199 was observed in
      GBM, the mesangial matrix, BBM, the tubular basement membrane, and the
      interstitium. Increased intensity of JK132 was observed in the mesangial matrix,
      BBM, and the tubular basement membrane, but was not remarkable in GBM or the
      interstitium. In contrast, biopsy specimens of CTN showed increased intensity of
      JK132 in GBM, the mesangial matrix, BBM, the tubular basement membrane and the
      interstitium. CONCLUSION: These results suggest that collagen IV is up-regulated
      in ADR. Differential staining of collagen IV with JK199 and JK132 in GBM and the
      interstitium may contribute to diagnose CTN.

PMID- 11455257
TI  - Results of a randomized, prospective, multicenter trial of mycophenolate mofetil
      versus azathioprine in the prevention of acute lung allograft rejection.
AB  - BACKGROUND: Although the use of mycophenolate mofetil (MMF) has reduced the
      incidence of acute rejection in heart and kidney allograft recipients, its role
      in lung transplantation remains controversial. Therefore, we conducted a
      randomized, prospective, open-label, multicenter study in lung transplant
      recipients to determine whether MMF decreases episodes of acute allograft
      rejection when compared with azathioprine (AZA). METHODS: Between March of 1997
      and January of 1999, 81 consecutive lung transplant recipients from two centers
      were prospectively randomized to receive cyclosporine, corticosteroids, and
      either 2 mg/kg per day of AZA or 1 g twice daily of MMF. The primary study
      endpoint was biopsy-proven acute allograft rejection over the first 6 months
      posttransplant. Secondary endpoints included clinical rejection, cytomegalovirus
      (CMV) infection, adverse events, and survival. Surveillance bronchoscopies were
      performed at 1, 3, and 6 months, or if clinically indicated. Pathologists
      interpreting the biopsy results were blinded to the randomization. Results were
      analyzed according to intention-to-treat. Between group comparisons of means and
      proportions were made by using two sample t tests and Fisher's exact tests,
      respectively. Six-month survival was calculated by the Kaplan-Meier method and
      compared by the log rank test. RESULTS: Thirty-eight patients were prospectively
      randomized to receive AZA, and 43 MMF. The incidence of biopsy proven grade II or
      greater acute allograft rejection at 6 months was 58% in the AZA group and 63% in
      the MMF group (P=0.82). The 6-month survival rates in the MMF and AZA groups were
      86% and 82%, respectively (P=0.57). Rates of CMV infection and adverse events
      were not significantly different between the two groups. CONCLUSIONS: Acute
      rejection rates and overall survival at 6 months are similar in lung transplant
      recipients treated with either MMF- or AZA-based immunosuppression.

PMID- 11455258
TI  - Urine macrophage migration inhibitory factor concentrations as a diagnostic tool
      in human renal allograft rejection.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory
      cytokine that is a potent activator of macrophages and T cells. Previous studies
      have shown that local MIF production is increased in acute renal allograft
      rejection, suggesting that it may play an important role in the rejection
      process. AIMS: To determine if urine and serum MIF concentrations: (1) are
      increased in acute rejection, and (2) can be used as noninvasive tools to
      discriminate between acute rejection (AR) and cyclosporine nephrotoxicity (CyA
      toxicity). METHODS: In a prospective study of nine renal allograft patients (five
      acute rejection and four stable), serial urine MIF concentrations were measured
      by ELISA in the first 14 days after transplantation. In a retrospective study,
      MIF concentrations in urine and serum were measured in 24 patients who were
      biopsied for acute renal transplant dysfunction (11 AR, 13 CyA toxicity). Urine
      and serum MIF were also measured in 23 stable renal transplant patients and 10
      normals. RESULTS: MIF was readily detected in the urine of normal healthy
      controls (106+/-61 pg/micromol creatinine). In the prospective study, the urinary
      MIF concentration was increased substantially on day 1 posttransplantation and
      subsequently fell in parallel with the serum creatinine. However, urine MIF
      increased before episodes of biopsy proven acute rejection. The retrospective
      study showed that urine MIF concentrations in patients with AR were increased 5
      fold compared to normal controls (439+/-313 pg/micromol Cr; P<0.01). In contrast,
      urine MIF concentrations in CyA toxicity were not significantly different to
      normal controls (145+/-119 pg/micromol Cr; P=NS). A marked increase in MIF
      immunostaining was seen in biopsies of AR, but not in CyA toxicity. No
      significant differences were evident in serum MIF levels between normals and any
      transplant patient group. CONCLUSIONS: These results suggest that measurement of
      urine MIF concentration may be useful in monitoring renal transplant patients for
      acute rejection and as a discriminator from cyclosporine nephrotoxicity.

PMID- 11455259
TI  - Pancreas transplantation: the histologic morphology of graft loss and clinical
      correlations.
AB  - BACKGROUND: Graft losses due to leaks, bleeding, thrombosis, infections, and
      early pancreatitis are grouped together under the category of technical failure.
      Among these complications, massive vascular thrombosis continues to be the most
      important cause of early graft loss due to technical failure. Pathological
      evaluation of most allografts lost early in the posttransplantation period shows
      vascular thrombosis with associated proportional parenchymal necrosis. The
      morphological findings in allografts that are considered to be lost due to
      technical failure has not been systematically addressed. In particular, the role
      of acute rejection in early graft loss has not been well studied. METHODS:
      Seventy-four consecutive pancreas graft pancreatectomies were studied
      histologically to evaluate for thrombosis (recent versus organized), type of
      vessel involved by thrombosis (arteries, veins, or both), acute rejection grade,
      chronic rejection grade, endotheliitis, transplant arteritis, coagulation
      necrosis, acute pancreatitis, presence of infectious organisms, transplant
      (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta
      islet cells, and immunoglobulin and complement deposition. The histological
      findings were correlated with donor and recipient data as well as clinical
      presentation. RESULTS: In 23 out of 39 grafts lost in the first 4 weeks
      posttransplantation, the only pathological changes found were vascular thrombosis
      and bland ischemic parenchymal necrosis. In these cases, no underlying vascular
      pathology or any other specific histological change was identified. Most of these
      grafts (78%) were lost in less than 48 hr and all in the first 2 weeks
      posttransplantation. Massive vascular thrombosis occurring in an otherwise
      histologically normal pancreas was the most common cause of graft loss in the
      first 4 weeks posttransplantation (59%). In most of the remaining cases (33%),
      although the clinical presentation suggested technical failure, there was clear
      histological evidence that the massive thrombosis resulted from vascular injury
      due to immune damage (acute and hyperacute rejection). Increased incidence of
      early graft thrombosis was seen in grafts from older donors and longer cold
      ischemia times. After the first month posttransplantation, graft pancreatectomies
      revealed a wider variety of pathological processes that included severe acute
      rejection, combined acute and chronic rejection, chronic rejection, and
      infections. Acute and chronic vascular thrombosis in large and small vessels was
      commonly seen at all times posttransplantation; chronic, organized thrombosis was
      strongly associated with chronic rejection. CONCLUSIONS: (a) Early acute
      thrombosis occurring in a histologically normal pancreas defines a true technical
      failure. This study showed that acute rejection leading to massive thrombosis,
      which clinically simulates technical failure, results in a significant proportion
      of early graft losses. (b) Systematic histological evaluation of failed grafts is
      absolutely necessary for the accurate classification of the cause of graft loss.
      (c) There is morphological evidence that chronically ongoing thrombosis is an
      important, common, contributing factor for late graft loss.

PMID- 11455260
TI  - Fibrinolytic preflush upon liver retrieval from non-heart beating donors to
      enhance postpreservation viability and energetic recovery upon reperfusion.
AB  - BACKGROUND: Our objective was to evaluate graft equilibration with high viscosity
      (University of Wisconsin solution [UW]) or low viscosity (Bretschneider's
      histidine-tryptophan-ketoglutarate [HTK]) during liver procurement from non-heart
      beating donors (NHBD) and the potential impact of a preceding fibrinolysis with
      streptokinase on postpreservation viability. METHODS: After 60 min of cardiac
      arrest, rat livers were perfused by gravity (60 cm H2O) via the portal vein with
      either 60 ml of HTK, 20 ml of UW, or 20 ml of Ringer's solution (22 degrees C
      including 7500U of streptokinase) and, subsequently, 20 ml of UW. After 24 h of
      storage at 4 degrees C, viability of the livers was assessed upon isolated
      reperfusion in vitro. RESULTS: Magnetic resonance imaging revealed severe
      perfusion deficits, which were mildly attenuated with HTK, upon flush-out with
      UW. After preflush with streptokinase, a mostly homogenous distribution of the
      preservation solution was observed throughout the liver tissue. The choice of the
      flush-out solution (UW or HTK) had no influence on parenchymal enzyme leakage,
      hepatic bile production, or tissue levels of ATP after reperfusion of the livers.
      Fibrinolytic preflush, however, resulted in a relevant and significant
      improvement of structural integrity as well as functional and metabolic recovery.
      CONCLUSIONS: Compromised vascular tissue perfusion upon organ harvest in NHBD
      triggers graft dysfunction after cold storage and can easily be circumvented by
      temporary fibrinolysis before graft retrieval.

PMID- 11455262
TI  - Trafficking of host- and donor-derived dendritic cells in rat cardiac
      transplantation: allosensitization in the spleen and hepatic nodes.
AB  - BACKGROUND: Kinetics and role of host and donor dendritic cells (DCs) in
      transplantation immunity are still ill-defined. Using a rat cardiac
      transplantation model, we studied DC trafficking and sites for allosensitization.
      METHODS: Host and donor DCs were defined as host- or donor-type class II major
      histocompatibility complex antigen single-positive cells by double
      immunostaining. Proliferative response of both donor and host cells were also
      analyzed. RESULTS: Host DCs were recruited to the graft soon after
      transplantation. These cells represented definitive precursors because of high
      labeling index by a continuous bromodeoxyuridine infusion, their small round
      shape, and their putative bone marrow origin. Donor interstitial DCs showed a
      significant self-replicating capability. Both recruited host DCs in a regraft
      experiment and donor DCs preferentially performed blood-borne migration to the T
      cell area of host spleen. Furthermore, they also migrated to the T-cell area of
      hepatic lymph nodes after executing the sinusoids-lymph translocation as a novel
      pathway for these DCs. Selectively at their migration sites, a strong T-cell
      proliferative response occurred, which preceded that in the graft tissues.
      Removal of spleen and hepatic lymph nodes significantly prolonged the mean graft
      survival time. CONCLUSION: We conclude that allogeneic heart transplantation
      induces the recruitment of host DC precursors to the graft tissues and the blood
      borne migration of both recruited host and donor DCs to the host spleen and
      hepatic nodes where effector cells are predominantly sensitized.

PMID- 11455261
TI  - Effects of immunosuppressive treatment on host responses against intracerebral
      porcine neural tissue xenografts in rats.
AB  - BACKGROUND: Embryonic xenogeneic neural tissue is an alternative for
      transplantation in Parkinson's disease, but immune responses limit the
      application. The aims of this study were to enhance the in vitro viability rates
      by donor tissue pretreatment; to compare the efficacy of cyclosporine A (CsA) and
      tacrolimus (FK) in inhibiting xenograft rejection in rats; to evaluate additional
      inductive therapy with prednisolone (PRE) or mycophenolate mofetil (MMF).
      METHODS: Tirilazad (a lipid peroxidase inhibitor) or FK and acYVAD-cmk (a caspase
      inhibitor), were added to embryonic porcine ventral mesencephalic tissue and
      viability was assessed in vitro. Tirilazad-treated tissue was grafted to the
      striatum of rats that were either left untreated or immunosuppressed with FK (1
      mg/kg) or CsA (15 mg/kg) alone or in combination with a 2-week PRE (20 mg/kg) or
      MMF (40 mg/kg) induction course. Xenograft survival and host responses were
      determined using immunohistochemistry. RESULTS: Pretreatment with tirilazad
      enhanced tissue survival in vitro. After transplantation into untreated controls,
      there was no graft survival at twelve weeks. Neural cell counts were
      significantly improved in immunosuppressed recipients, but there were no
      differences between the treatment groups. Additional inductive treatment reduced
      the infiltration with CD4+ and CD8+ cells, and macrophage infiltration was
      reduced compared with animals given CsA or FK alone. CONCLUSION: Pretreatment of
      the donor tissue with free-radical scavengers reduces cell loss caused by tissue
      trauma. Porcine neural tissue xenografts survive significantly better in animals
      immunosuppressed with either FK or CsA. Additional inductive treatment with PRE
      or MMF reduced the infiltration of host cells into the xenografts.

PMID- 11455263
TI  - Increased generation of reactive oxygen species in isolated rat fatty liver
      during postischemic reoxygenation.
AB  - BACKGROUND: Whether fatty infiltration of the liver influences the generation of
      reactive oxygen species (ROS) during reperfusion is unclear. Thus, this study
      aimed to compare the ROS formation that occurs during postanoxic reoxygenation in
      isolated normal and fatty livers. METHODS: Isolated livers from fed Sprague
      Dawley rats with normal or fatty livers induced by a choline-deficient diet were
      reperfused at 37 degrees C for 60 min with an oxygenated medium containing 10
      microM of lucigenin after 1 hr of warm ischemia. Superoxide anion generation was
      assessed by the chemiluminescence (CLS) signal emitted from the organ surface.
      The hepatic content of malondialdehyde (MDA) and glutathione was determined at
      the end of reperfusion. Tissue injury was evaluated by the liver histology and
      the alanine aminotransferase (ALT) release in the perfusate. RESULTS: CLS started
      rapidly with reoxygenation and it diffused to the whole organ in both groups.
      However, CLS emission was significantly higher in fatty liver (after 10 min:
      812.425+/-39.898 vs. 294.525+/-21.068 photons/cm2/sec; P<0.01). A greater
      concentration of MDA was measured at the end of reoxygenation in fatty liver.
      Finally, the liver histology and the ALT release indicated a greater injury in
      steatotic than normal liver. CONCLUSIONS: The CLS technique allows a direct
      visualization and comparison of ROS generation from the organ surface. Fatty
      infiltration increases ROS generation in the liver during postischemic
      reoxygenation, likely leading to the greater lipid peroxidation observed in these
      experiments. The increased oxidative stress may contribute to the reduced
      tolerance of steatotic livers to ischemia-reperfusion injury.

PMID- 11455264
TI  - A subpopulation of mitochondria prevents cytosolic calcium overload in
      endothelial cells after cold ischemia/reperfusion.
AB  - BACKGROUND: Calcium represents a key mediator of cold ischemia/reperfusion (CIR)
      injury presumably by affecting mitochondrial function. In this study, we
      investigated cellular and mitochondrial changes of calcium homeostasis in
      sublethally damaged human endothelial cells. METHODS: Changes in cellular and
      mitochondrial calcium concentrations were studied after cold ischemia in
      University of Wisconsin solution for 12 hr and reperfusion in ringer solution.
      Cytosolic-free calcium concentration ([Ca2+]c) and mitochondrial-free calcium
      content ([Ca2+]m) were analyzed by fura-2 and rhod-2 fluorescence, respectively.
      Pretreatment of cells with ruthenium red (RR) or a H+-ionophore was used to
      inhibit mitochondrial calcium uptake. Mitochondrial membrane potential
      (DeltaPsim) was measured by 5,5',6,6'-tetrachloro- 1,1',3,3'
      tetraethylbenzimidazolylcarbocyanine iodide and 3,3'-dihexyloxacarbocyanine
      iodide fluorescence. RESULTS: Twelve-hr cold ischemia did not induce apoptosis in
      endothelial cells. In such sublethally damaged cells, [Ca2+]c rose from
      approximately 20 nmol/L after cold ischemia to approximately 120 nmol/L during
      reperfusion. Pretreatment with RR leads to an approximately 5-fold rise in
      [Ca2+]c. Image analysis revealed a significant increase of [Ca2+]m in a
      subpopulation of mitochondria during reperfusion. This was not the case in RR
      pretreated cells. DeltaPsim decreased significantly during cold ischemia and was
      sustained during reperfusion. The loss of DeltaPsim can be related to a reduced
      portion of mitochondria exhibiting high DeltaPsim. CONCLUSIONS: Our results
      suggest that cytosolic calcium influx during CIR is buffered by a selective
      portion of mitochondria in human umbilical vein endothelial cells. These
      mitochondria protect cells against cytosolic calcium overload and probably
      against subsequent cell injury.

PMID- 11455265
TI  - Apoptosis and allograft rejection in the absence of CD8+ T cells.
AB  - BACKGROUND: The requirement for cytotoxic T lymphocytes during allograft
      rejection is controversial. We previously demonstrated that CD8+ T cells are not
      necessary for allograft rejection or for the induction of apoptosis in rat small
      intestinal transplantation. In this study, we examined the mechanisms of
      apoptosis and rejection after liver transplantation in the absence of CD8+ T
      cells. METHODS: Either Lewis or dark agouti rat liver grafts were transplanted
      into Lewis recipients to create syngeneic and allogeneic combinations. CD8+ T
      cells were depleted in an additional allogeneic group by treatment with OX-8 mAb
      on day -1 and day 1 after liver transplant. RESULTS: Apoptosis and rejection were
      observed in both the CD8+ T cell-depleted allogeneic and allogeneic grafts by
      hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labeling staining, and radiolabeled-annexin V in vivo imaging.
      Granzyme B and FasL were expressed in all allogeneic transplants, including those
      depleted of CD8+ T cells, indicating that a mononuclear cell other than a CD8+ T
      cell can be the source of these molecules during allograft rejection. Activation
      of the caspase cascade was detected in all rejecting allografts. Caspases 3, 8,
      and 9 were activated at similar significantly elevated levels in both allogeneic
      and CD8+ T cell-depleted liver grafts. CONCLUSION: These data indicate that in
      the absence of CD8+ T cells an alternative pathway, associated with granzyme B
      and FasL expression and activation of the caspase cascade, can mediate apoptosis
      and graft rejection.

PMID- 11455266
TI  - sTNFRI and sTNFRII synthesis by fine-needle aspiration biopsy sample cultures is
      significantly associated with acute rejection in kidney transplantation.
AB  - BACKGROUND: Previously we reported that cultures of fine-needle aspiration biopsy
      (FNAB) samples synthesize different cytokine pattern depending on the alloimmune
      response towards the kidney graft. However, we failed to find a clear picture for
      growth factors implicated in early T-cell activation (interferon-gamma,
      interleukin [IL]-4, IL-12), although we observed that interleukin-1 receptor
      antagonist (IL-1ra) was associated with absence of acute rejection. We have now
      studied tumor necrosis factor-alpha (TNF-alpha) and its two soluble receptors,
      sTNFRI and sTNFRII, IL-1beta and soluble IL-1 receptor II (sIL-1RII), and
      leukemia inhibitory factor (LIF), all potential modulators of T-cell activation.
      METHODS: Sixty-six cadaver kidney transplants (KTX) were divided into four
      groups: group 1, day 7 after KTX, stable (n=30); group 2, day 7 after KTX, 8+/
      4.5 days before acute rejection (n=12); group 3, first day of acute rejection
      (n=17); and group 4, day 14 after KTX, stable (n=32). Patients from groups 1 and
      4 remained rejection-free for the first 6 months. All rejection episodes were
      confirmed by core renal biopsy. FNAB samples were cultured according to our
      published methodology, and culture supernatants were collected at 48 hr and
      analyzed by ELISA for IL-1beta, sIL-1RII, TNF-alpha, sTNFRI, sTNFRII, and LIF.
      Serum levels for sIL-1RII, sTNFRI, and sTNFRII were also measured. RESULTS: FNAB
      cultures from groups 1 and 4 synthesized significantly lower amounts of sTNFRI
      and sTNFRII than those from either groups 2 or 3. Both sTNFRI and sTNFRII reached
      high positive and negative predictive values for acute rejection. IL-1beta and
      sIL-1RII were synthesized by all groups but without differences. No trace of LIF
      and TNF-alpha was found. sTNFRII was significantly higher in serum from group 3.
      CONCLUSIONS: Both TNF receptors were positively associated with acute rejection
      and were good predictors of impending acute rejection. The ratio of sIL-1RII over
      IL-1 (together with IL-1ra that we previously measured in FNAB cultures) suggests
      that IL-1 actions may be inhibited with current immunosuppression early after
      transplantation.

PMID- 11455267
TI  - Increased endothelin-1 associated with bacterial infection in lung transplant
      recipients.
AB  - BACKGROUND: Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its
      pathogenic role in pulmonary fibrosis and certain inflammatory airway diseases is
      now well known. Its production is, in part, triggered by infectious processes.
      Episodes of infection are suspected to be involved in the development of
      bronchiolitis obliterans syndrome (BOS), which is the main feature of chronic
      lung rejection and the major factor limiting the long-term survival of
      transplanted patients. We postulated that ET-1 is upregulated during infectious
      complications arising from the graft and that this could partly explain the
      remodeling of airway structures observed in BOS. We, therefore, set up this study
      to assess ET-1 expression in relation to complications of the graft in human lung
      transplant recipients. METHODS: ET-1 mRNA was quantified by reverse transcription
      competitive polymerase chain reaction in cells from 119 samples of
      bronchoalveolar lavage (BAL) fluid from 17 lung transplant recipients. ET-1 and
      big ET-1 proteins were assessed in BAL cell culture supernatants by enzyme
      immunoassay. Transbronchial biopsies (n=21) were stained immunohistochemically
      for ET-1 receptors. RESULTS: Episodes of bacterial infection strongly correlated
      with increased ET-1 mRNA and protein expression. ET-1 receptors were also
      upregulated during these episodes, especially on endothelial and smooth muscle
      cells. Five of the seven patients with the highest ET-1 levels subsequently
      developed BOS. CONCLUSIONS: These results raise the possibility that ET-1, part
      of whose production is triggered by infectious postgraft complications, might
      play a role in the development of BOS through its potential effects on airway
      remodeling.

PMID- 11455268
TI  - Persistence of stable intragraft cell chimerism in rat liver allografts after
      drug-induced tolerance.
AB  - BACKGROUND: Drug-induced tolerance of rat liver allografts is well documented. We
      analyzed cellular events during immunosuppressive therapy on day (d) 10 and in
      the late phase (d 100) after transplantation to assess for characteristics in the
      intrahepatic leukocyte (IHL) population in the phase of tolerance. METHODS: Lewis
      rats served as recipients of Dark Agouti rat livers. Temporary immunosuppression
      with either cyclosporine (CsA) monotherapy (3 mg/kg/d) or triple therapy that
      consisted of a subtherapeutic CsA dosage (0.25 mg/kg/d) and monoclonal antibodies
      directed against the interleukin-2 receptor (IL-2R, CD25) and the intercellular
      adhesion molecule-1 (ICAM-1, CD54) was administered from postoperative d 0 to d
      13. Cell migration and cell activation within liver grafts was assessed by
      standard histology and flow cytometry. IHL apoptosis was detected by terminal
      deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL).
      RESULTS: Both CsA monotherapy and triple therapy prolonged liver allograft
      survival to more than 100 d and led to the induction of donor-specific tolerance.
      Untreated recipients rejected their allografts within 14 d. In both groups, donor
      specific IHLs initially dropped to 18% to 25% on d 10, but they rebounded to as
      much as 40% on d 100 as a common characteristic of both groups. Within this
      population, donor-specific T cells were dominant. In both groups, increased
      numbers of activated (IL-2R+) CD8+ T lymphocytes were present on d 100. No
      accumulation of apoptotic IHL was observed on d 100. Their proportion was
      unchanged in the triple therapy group and slightly decreased in the CsA group
      compared to the syngeneic controls. CONCLUSIONS: The present study reveals that
      tolerant liver allografts are repopulated by donor-specific T lymphocytes. This
      phenomenon is independent of the type of applied immunosuppression. The
      persistence of activated CD8+ T cells in the phase of proven donor-specific
      tolerance on d 100 indicates that liver tolerance is associated with the state of
      a permanent intragraft immune activation. It seems that the coexistence of donor
      cells with infiltrating recipient cells within liver grafts, termed intrahepatic
      cell chimerism, is characteristic for tolerated liver allografts.

PMID- 11455269
TI  - Extrapancreatic pseudoaneurysm after pancreas transplantation.
AB  - Pseudoaneurysms after pancreatic transplantation are an infrequent event. Repair
      usually involves removal of the transplant. We describe a patient with a
      pseudoaneurysm associated with pancreatic transplantation. The pseudoaneurysm
      originated from the external iliac artery distal to the donor Y-graft
      anastomosis. Diagnosis was made by duplex ultrasound. Surgical repair was
      effected through a retroperitoneal incision enabling vascular control. The
      patient has done well postoperatively, and with 1-year follow-up, continues to
      have normal renal and pancreatic allograft function.

PMID- 11455270
TI  - Posttransplant bone disease: a case illustrating dramatic improvements in bone
      density with vitamin D replacement therapy.
AB  - Although bisphosponates are proposed as first-line treatment for posttransplant
      bone disease they are not optimal in all situations. A kidney transplant
      recipient developed hypercalcemia from mobilization of extraskeletal calcium. He
      had low serum parathyroid hormone and vitamin D; high calcium excretion; and
      normal calcium intake. Bone biopsy revealed severe osteomalacia. Bisphosphonates,
      used in the early treatment of acute hypercalcemia, were not indicated to treat
      osteomalacia. However, over several months serum calcium declined sufficiently to
      allow treatment of the bone disease with oral calcitriol. Dual-energy
      radiographic absorptiometry over the next 2 years documented dramatic
      improvements in bone density (percent of young-normal controls) : from 63 to 85%,
      at the lumbar spine; from 38 to 67%, at the femoral neck. This response to
      treatment could not have been achieved with an antiresorptive strategy. Optimal
      management of posttransplant bone disease requires a diagnostic approach, which
      considers all plausible contributing factors.

PMID- 11455271
TI  - Emergent lung retransplantation after discovery of two primary malignancies in
      the donor.
AB  - A 50-year-old woman underwent single lung transplantation for advanced chronic
      obstructive pulmonary disease. Shortly after the procedure, it was discovered
      that the donor suffered from both a renal cell carcinoma and a spindle-cell
      sarcoma of the ascending aorta, which had metastasized to the spleen. The patient
      was emergently listed for a retransplantation and underwent bilateral lung
      transplantation after a new donor became available 4 days after the initial
      transplantation procedure. After 24 months, the patient is without evidence of
      malignancy. This case illustrates the role of immediate retransplantation for
      patients who have inadvertently received thoracic organs from donors harboring
      occult malignancies.

PMID- 11455272
TI  - A survey: the prevalence of laparoscopic donor nephrectomy at large U.S.
      transplant centers.
AB  - BACKGROUND: There is controversy whether laparoscopic donor nephrectomy (LDN) is
      the procedure of choice for live kidney donors. The purpose of this survey
      therefore was to determine the current practices, attitudes, and plans regarding
      LDN in high-volume renal transplant centers. METHODS: Medical directors of the 31
      highest volume kidney transplant centers were surveyed via telephone. Kidney
      transplant data for 1998 and 1999 were collected. RESULTS: The surveyed centers
      performed 5213 transplantations in 1998, representing 43% of all kidney
      transplantations done nationally. Twelve (39%) of the 31 centers performed LDN in
      1998, increasing to 20 (65%) of 31 in 1999. Of 1174 live donor operations
      performed by the 20 centers in 1999, 365 (31%) were LDNs. Among the surveyed
      centers, four had no plans to begin an LDN program. The most commonly cited
      incentive for LDN was "shorter recovery time," whereas the most common
      disincentive was "concern about graft quality." A combination of observation and
      animate laboratory was the most commonly reported method of learning the LDN
      procedure. Six-month follow-up interviews found that 26 (84%) of 31 centers had
      performed LDN; only 1 of the 31 centers had no plans to perform LDNs.
      CONCLUSIONS: LDN may be the de facto procedure of choice for live donors within
      the next year. Efforts should now focus on improving techniques for performing
      and teaching this procedure.

PMID- 11455273
TI  - Reconstruction of middle hepatic vein of a living-donor right lobe liver graft
      with recipient left portal vein.
AB  - Venous outflow problems in right lobe, living-donor liver transplantation are
      uncommon, but devastating when they occur. We describe the successful use of the
      recipient's left portal vein as an interposition graft to drain a dominant middle
      hepatic vein in a right lobe liver transplant. Two weeks after transplantation,
      the vein graft accounted for 56% of the total venous outflow of the liver.

PMID- 11455274
TI  - The effects of CTLA-4Ig on acute lung allograft rejection: a comparison of
      intrabronchial gene therapy with systemic administration of protein.
AB  - BACKGROUND: Blockade of T-cell costimulation by local delivery of an adenoviral
      vector encoding for CTLA-4Ig and systemic administration of the protein are
      compared in a rat lung allograft model. METHODS: Left lungs of Brown Norway rats
      (RT1n) were transplanted into Lewis (RT11) recipients in four groups of six
      animals each: 1) no treatment; 2) intrabronchial transduction of donor lung with
      adenovirus encoding mCTLA-4Ig (adeno-mCTLA-4Ig); 3) intrabronchial transduction
      with empty adenovirus; and 4) intraperitoneal injection of mCTLA-4Ig. Grading of
      rejection, mCTLA-4Ig measurement in serum and bronchial washings, RT-PCR for
      virally encoded transcripts, and immunohistochemistry for mCTLA-4Ig were carried
      out 4 days later. RESULTS: Intrabronchial transduction with adeno-mCTLA-4Ig
      resulted in detectable transgene expression in graft tissue and bronchial fluid
      but not in serum. Significant reduction in rejection grade (from grade 3 to 2)
      occurred after systemic mCTLA-4Ig but not adeno-mCTLA-4Ig transduction.
      CONCLUSION: Local expression of immunomodulatory proteins can be achieved within
      lung allografts by intrabronchial delivery of adenoviral vector but may not
      significantly modify acute rejection.

PMID- 11455275
TI  - Case 2: Post-transplant diabetes mellitus in renal transplantation.

PMID- 11455276
TI  - Tricuspid valve involvement in combined mitral and aortic valve surgery.
AB  - BACKGROUND: Combined mitral and aortic valve disease requiring surgery may
      involve the tricuspid valve as well. Our treatment policy is conservative
      especially for tricuspid regurgitation which is operated on when severe only.
      METHODS: A retrospective study was performed at a tertiary and secondary referral
      center for cardiovascular disease. Over a 15-year period, 65 consecutive patients
      underwent aortic and mitral surgery with concomitant tricuspid regurgitation
      and/or stenosis. Fifty-five/65 (85%) patients were in NYHA class III-IV. Fifty
      eight/65 (89%) patients had tricuspid regurgitation secondary to right chamber
      dilatation and 7/65 (11%) had tricuspid stenosis and/or regurgitation because of
      previous endocarditis. Twenty-two/65 (34%) tricuspid valves were operated on:
      18/22 (82%) de Vega annuloplasty, 2/22 (9%) commissurotomies and 2/22 (9%)
      prosthetic valves. Mortality and complications were recorded during a mean follow
      up of 5.3 yrs (range, 6 months-15.3 yrs). Event-free survivals were determined
      using the Kaplan-Meier method. RESULTS: Hospital mortality was 6.2% (4/65) and
      the complication rate was 18.5% (12/65). The freedom from late valve related
      mortality and morbidity at 5, 10 and 15 years was 86+/-5.5%, 81.9+/-6.8%, and
      81.9+/-6.8% respectively. One valve related complication was due to the tricuspid
      valve. At last follow-up, 87% (47/54) of the survivors were in NYHA class I-II.
      CONCLUSIONS: With a conservative policy of tricuspid valve intervention,
      functional results of this patient population are good and long-term valve
      related morbidity and mortality are mainly related to the mitral and aortic valve
      procedures.

PMID- 11455277
TI  - Off-pump coronary artery bypass grafting. Excellent results in a group of
      selected high-risk patients.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting (OPCABG) has assumed an
      increasing role in many surgical practices. The ideal candidate has not been
      defined, but high-risk patients seem to benefit most when cardiopulmonary bypass
      (CPB), aortic cross clamping and cardioplegic arrest are avoided. METHODS:
      Fourteen high-risk patients (age 52 to 81 years, 1 female, EF 44%+/-8, Parsonnet
      score 23+/-4) were studied. They presented with acute coronary syndroms on
      platelet glycoprotein IIb/IIIa antagonists, acute myocardial infarction,
      worsening renal failure, decompensating ischemic cardiomyopathy, religious
      beliefs and denial of blood transfusion, and severe peripheral/cerebrovascular
      disease (total bilateral internal carotid artery occlusion and/or >90% stenosis).
      These patients underwent OPCABG via sternotomy with the intention of complete
      coronary revascularization. RESULTS: An average of 2.3 grafts/patient were
      performed and the posterior descending artery (PDA) and marginal branches of the
      circumflex artery (LCX) were grafted in 79% of the patients. There were 3 events
      of intraoperative cardiac arrest precipitated by occlusion of right coronary
      artery (RCA) or positioning a cardiomegaly heart leading to immediate
      intravascular shunting (2) and/or conversion to CPB (1). One patient was
      converted to CPB and graft revision (intraoperative ultrasound and probing). The
      mortality rate was 0% and one stroke was observed on post-operative day 1.
      Coronary angiography (n=6) showed no significant stenosis. CONCLUSIONS: OPCABG
      complete revascularization is feasible in high-risk patients with low morbidity
      and mortality and excellent early RESULTS: OPCABG may be indicated in patients on
      platelet receptor antagonists preventing bleeding complications. Cardiomegaly can
      cause difficult off-pump LCX and PDA exposure and stabilization. RCA grafting off
      pump is less tolerated and PDA grafting is preferred. High-risk patients for CPB
      are the ones who may benefit the most from OPCABG.

PMID- 11455278
TI  - Conversion of extracorporeal membrane oxygenation to non-pulsatile left
      ventricular assist device. Is it out-of-date for non-pulsatile LVAD?
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides an immediate
      support for acute deterioration of hemodynamic and pulmonary status, but what is
      the best decision for these critical patients? Biventricular assist device (BVAD)
      or left ventricular assist device (LVAD)? We proposed a protocol of step-by-step
      conversion from ECMO to LVAD after assurance of the reversibility of right
      ventricle and pulmonary function. METHODS: After femoral venoarterial ECMO was
      inserted for the critical patients, the left atrial drainage was added to the
      ECMO firstly and the femoral arterial inflow was shifted to the ascending aorta
      for preventing possible peripheral vascular complications. Temporary clamp of
      right heart drainage was tried to test right heart function 24 to 48 hours later.
      The sweep gas flow of oxygenator could be reduced gradually to test the pulmonary
      function. Therefore, the right heart drain and the oxygenator could be withdrawn
      to become a non-pulsatile LVAD or shift to pneumatic LVAD directly. There were
      four clinical experiences with successful conversion without temporary right
      ventricular assist device. RESULTS: All of them were able to convert their ECMO
      to LVAD smoothly in 8.0+/-2.5 days. Three of them were shifted to non-pulsatile
      LVAD, and one was converted to HeartMate. All but one could be weaned from the
      ventilator. No BVAD was needed in these patients. Due to the shortage of donor
      hearts, only one had the chance to undergo heart transplantation. CONCLUSIONS:
      The protocol did provide a good guideline for decision-making for those under
      ECMO support necessitating bridge to transplantation.

PMID- 11455279
TI  - Conventional and conventional plus modified ultrafiltration during cardiac
      surgery in high-risk congenital heart disease.
AB  - BACKGROUND: This prospective nonrandomized study is the critical assessment of
      conventional ultrafiltration (CUF) and modified ultrafiltration (MUF) techniques
      and their efficiency in congenital heart disease surgeries. Use of
      cardiopulmonary bypass (CPB) in children is associated with body water retention
      as a consequence of prime volume and systemic inflammatory reaction. The CUF
      during CPB has reduced body water excess and the MUF after CPB, removes
      inflammatory mediators, improves hemodynamic performance, and decreases
      transfusion requirements. METHODS: Forty-one patients, aged 9 to 36 months,
      submitted to surgical correction for cardiac defects, using CPB, were divided
      into 2 similar groups: CUF (21 patients) operated between 1996-1997 were
      ultrafiltered during CPB, and CUF+MUF, (20 patients) operated between 1997-1998
      and ultrafiltered during and after CPB. Postoperative duration of ventilator
      support, pediatric intensive care unit stay (PICU), hospital stay of the groups
      with and without preoperative pulmonary hypertension (PH), as well as transfusion
      requirement, hematocrit and platelet counts were compared. RESULTS: There were no
      technical complications and a significant ultrafiltrate in the CUF+MUF group was
      observed as compared to the CUF group. No significant differences were observed
      between the CUF and CUF+MUF groups regarding ventilatory support, PICU stay and
      hospital stay. Requirements for red cell transfusion, Ht and platelet counts were
      not statistically different. CONCLUSIONS: CUF and CUF+MUF were safe and efficient
      methods for patient stabilization independent of diagnosis and complexity of
      surgery. Future clinical evaluation should address a larger population of
      patients to research the different variables.

PMID- 11455280
TI  - pH paradox and neonatal heart.
AB  - BACKGROUND: To evaluate the functional status of the Na+/H+ exchanger in the
      neonatal heart. METHODS: On the Langendorff system, isolated neonatal rabbit
      hearts were arrested by using cardioplegia with or without a specific Na+/H+
      exchanger blocker, 5-(N,N dimethyl) amiloride (DMA) (20 microM). Ischemic period
      was 40 minutes at 37 degrees C or 120 minutes at 20 degrees C before 30 minutes
      of reperfusion at 37 degrees C. When DMA was added to the cardioplegia solution,
      it was also added to the reperfusate for the first 5 minutes of reperfusion (20
      microM). RESULTS: Postischemic developed pressure was 50.3+/-7.1 mmHg in the DMA
      group versus 25.9+/-6 mmHg in the control group (p<0.05) at 37 degrees C and
      74.8+/-14.6 mmHg in the DMA group versus 60.6+/-11.5 mmHg in the control group
      (p<0.05) at 20 degrees C. Postischeimic diastolic pressure was 40.4+/-3.3 mmHg in
      the DMA group versus 28.4+/-7 mmHg in the control group (p<0.05) at 37 degrees C
      and 9.6+/-3.1 mmHg in the DMA group versus 15+/-3.7 in the control group (p<0.05)
      at 20 degrees C. Creatine kinase washout was 296+/-97 IU/L in the DMA group
      versus 1253+/-537 IU/L in the control group (p<0.05) at 37 degrees C and 370+/
      156 IU/L in the DMA group versus 524+/-104 IU/L in the control group (p<0.05) at
      20 degrees C. CONCLUSIONS: 1) The Na+/H+ exchanger is active in the neonatal
      heart. 2) The Na+/H+ exchanger plays a key-role in the pathogenesis of
      reperfusion injury of the neonatal myocardium. 3) This exchanger is sensitive
      even for low H+ transmembrane gradients and even under hypothermic conditions.

PMID- 11455281
TI  - Prevention of aortic anastomotic hemorrhage. A simplified intraoperative testing
      technique.
AB  - BACKGROUND: Postoperative bleeding in aortic root aneurysms had represented a
      challenge. METHODS: Intraoperative testing of the annular or subannular aortic
      anastomosis, during procedures involving replacement of the aortic root, with
      either synthetic tube graft, a composite graft or an allograft is described. By
      reversing the flow of the LV vent and delivering cardioplegia into the left
      ventricle and thereby pressurizing the left ventricle and its outflow, this
      technique enables the surgeon to simulate the volume loaded heart, prior to
      completion of the distal anastomosis. A systematic assessment of the proximal
      suture line can then be undertaken. Portions of the proximal suture line,
      particularly the posterior aspect, are obscured if the inspection takes place
      after completion of both aortic anastomoses, the coronary attachments, as well as
      from the presence of the main pulmonary artery and by the distended aorta itself.
      RESULTS: The use of this method in 34 patients is described without untoward
      events related to this technique. CONCLUSIONS: The advantages of this technique
      are a rapid and safe assessment of the integrity of the proximal suture line bed.

PMID- 11455282
TI  - Atrial blood cyst in an adult with regurgitation of mitral and tricuspid valves.
AB  - Blood cysts of the heart are extremely rare in adults and usually involve valves
      or the left ventricle. Although two cases of blood cysts in the right atrium in
      adults have been reported, a cyst combined with a disorder of the valves has
      never been reported. We report a 52-year-old woman with a blood cyst that
      generated from the right atrial septum. Furthermore, the patient had
      regurgitation of both the mitral and tricuspid valves and then underwent surgical
      excision of the blood cyst, mitral valve plasty and tricuspid valve annuloplasty.
      We believe that it is possible to diagnose blood cysts with echocardiography, CT
      and magnetic resonance imaging. Echocardiography showed the cyst as a circle
      without a complete inner free-echo. CT and magnetic resonance imaging showed a
      mass with a non-enhanced inner structure. Furthermore, the latter showed a cyst
      that was enhanced by T1- but not T2-weighted images, indicating that the content
      of the cyst was a persistent substance such as blood. Concerning the generation
      of blood cysts, we hypothesize that heteroplastic growth arising from primitive
      pericardial mesothelium causes disorders of valves and blood cysts.

PMID- 11455283
TI  - Resection of a giant left main stem coronary artery aneurysm.
AB  - A 2 cm in diameter aneurysm of the left main stem was diagnosed in 1979. The
      aneurysm increased to 10 cm in diameter during 20 years. It was resected and
      successful bypass surgery was performed. No previous report was found of a giant
      true aneurysm involving the left main stem.

PMID- 11455284
TI  - Left ventricular apex venting during deep hypothermia in a case of difficult re
      entry into the mediastinum.
AB  - The cardiopulmonary bypass techniques of peripheral cannulations and deep
      hypothermia provide safe and controlled re-entry into the mediastinum, when the
      thoracic organs are contiguous with the sternum. In such cases, in order to
      prevent ventricular distention during cooling, left ventricular venting is very
      important but can be difficult. We made a small (3 cm) left-sided thoracotomy
      incision and inserted a left ventricular apical venting tube while cooling a
      patient with a large pseudoaneurysm of the ascending aorta, which was diagnosed
      12 years after aortic valve replacement. We found that this technique was easy,
      safe, and useful to prevent ventricular distention during cooling.

PMID- 11455285
TI  - Sudden death due to rupture of an omental metastatic tumor arising from cardiac
      angiosarcoma. A case report.
AB  - A 32-year-old man underwent surgical excision of a malignant hemangioendothelioma
      of the heart and received multidisciplinary treatment. Thirty-three months later,
      he underwent a second surgical treatment for a recurrent tumor of the posterior
      chest wall of the right thorax. Five months after this surgery (thirty-eight
      months after the initial surgery), a second recurrent tumor in the right thorax
      developed. Although radiotherapy and recombinant interleukin-2 were administered,
      anemia of unknown origin (hemoglobin 6.7 g/dl) developed. The patient died of
      sudden shock due to a rupture of an omental metastatic tumor. The patient
      survived for 41 months after the first surgical resection. We present this case
      because it is the first reported case of sudden death due to bleeding from an
      omental metastatic tumor, and because our patient was the second-longest survivor
      after surgical treatment for cardiac angiosarcoma.

PMID- 11455286
TI  - An unusual source of massive intra-abdominal hemorrhage during cardio-pulmonary
      bypass.
AB  - Intra-abdominal hemorrhage occurring while on cardio-pulmonary bypass (CPB) is a
      rare and potentially lethal event during coronary artery bypass procedures. We
      herein report an unusual case in which massive intra-abdominal bleeding during
      CPB originated from a previously undiagnosed ovarian tumor, leading to acute
      anemization and hemodynamic instability and requiring emergency gynecologic
      surgery.

PMID- 11455287
TI  - Mitral exposure technique for redo cardiac surgery. A left mediastinal pleurotomy
      and minimal adhesiotomy method.
AB  - We report an improved mitral exposure technique for mitral valve re-operation.
      Left mediastinal pleurotomy through a median sternotomy achieves rotation of the
      heart and excellent exposure of the mitral valve allowing the apex to drop
      posteriorly. We employed this technique in redo mitral valve surgeries for over a
      3-year period. This minimal adhesiotomy method is technically simple, safe and
      time-saving.

PMID- 11455288
TI  - Isolated replacement of the mitral leaflets and "Mercedes"-plastics of the giant
      left atrium: surgery for patients with left ventricle dysfunction and left atrium
      enlargement.
AB  - BACKGROUND: The main goal of the present surgery is to develop a new complex of
      surgical procedures for patients with long-standing mitral valve incompetence,
      severe left atrium (LA) and left ventricle (LV) enlargement (secondary
      cardiomyopathy). METHODS: Seven patients were operated on using a new technique.
      Normal LA shape and size were restored by symmetrical "Mercedes"-plastics of the
      posterior LA wall. Isolated strut chordae sparing mitral leaflets replacement
      (SChS-MLR) was performed for preserving annular-LV interaction and biomechanics
      of the LV contraction. In mitral position we implanted bileaflets Carbomedics
      (USA) prosthesis (in 6 patients) and a tilting disc MIKC prosthesis (Russia).
      Additionally RA plastics and TV De Vega plastics were performed in 4 patients.
      Diastolic and systolic functions of the LV, the size of the LA were under TEE and
      2D ECHO controls. RESULTS: All the patients were discharged from the hospital.
      After the operation the needs for inotropic support were minimal. We did not see
      any local LV wall motion abnormalities. The end diastolic volume and long-axis
      dimension of the LV did not have any tendency to grow. CONCLUSIONS: New surgical
      technique of isolated SChS-MLR together with the symmetrical restoration of the
      LA shape and size can be equivalent to reconstructive mitral valve surgery from
      the hemodynamical point of view and allows us to standardize the surgical
      technique for those patients with significant left heart enlargement.

PMID- 11455289
TI  - Valve-preserving surgery of the proximal aorta.
AB  - BACKGROUND: Surgical treatment of proximal aortic disease currently offers a
      variety of surgical options. Traditionally, replacement of the proximal aorta has
      been performed with a composite graft in most cases; supracommissural aortic
      replacement was the only alternative if preservation of the native aortic valve
      was attempted. Valve-preserving root operations currently allow us to avoid the
      disadvantages of prosthetic heart valves and completely eliminate aortic root
      pathology. METHODS: Between 10/95 and 5/99, 219 patients were treated for
      proximal aortic disease. The diagnoses included degenerative disease (n=158),
      acute dissection (n=48), and chronic dissection (n=13). Composite replacement of
      valve and root (n=99) was used only in patients with significant degeneration or
      stenosis of the aortic valve. For near-normal root dimensions supracommissural
      aortic replacement (n=44) was chosen. Root remodeling (n=60) and reimplantation
      of the valve within a vascular graft (n=16) were performed for aortic valve
      regurgitation and root dilatation. RESULTS: Overall hospital mortality was 5.7%;
      in elective operations, mortality was expectedly lower compared to emergency
      interventions (2.4% vs 16.3%; p<0.05). Hospital mortality for valve preserving
      procedures was similar (elective procedures 1.9%, emergency operations 9.5%). Two
      year freedom from aortic regurgitation grade II or higher was 89% for remodeling
      and 92% for reimplantation. Freedom from reoperation for secondary and increasing
      regurgitation at two years was 96% for remodeling and 100% after reimplantation.
      CONCLUSIONS: Using current techniques of valve preserving surgery, combined
      disease of the aortic valve, root, and extended segments of the aorta can be
      corrected without the disadvantages of prosthetic heart valves in the majority of
      patients. Further experience will define the relative role of the different
      operative modifications.

PMID- 11455290
TI  - A preoperative index of mortality for patients undergoing surgery of type A
      aortic dissection.
AB  - BACKGROUND: The aim of this study was to identify and stratify the most important
      preoperative factors for in-hospital death after surgery for type A aortic
      dissection. METHODS: From January 1985 to June 1998, 108 patients underwent
      surgery for type A aortic dissection. 89.9% of the patients had an acute type A
      dissection (AD), whereas 11.1% had a chronic dissection (CD). Cardiac tamponade
      and shock occurred in 22% and 14.8% of the patients, respectively. The location
      of the primary intimal tear was in the ascending aorta in 71.2% of the cases, in
      the arch in 16.6% and in the descending aorta in 7.4%. Univariate and
      multivariate analyses were conducted to identify non-embolic variables
      independently correlated to in-hospital death. A predictive model of in-hospital
      mortality was then constructed by means of a mathematical method with the
      variables selected from logistic regression analysis. RESULTS: The overall in
      hospital mortality rate was 20.3% (22/108 patients), being 9% for CD and 21.6%
      for AD. Emergent procedures had an in-hospital mortality rate of 47.6%, whereas
      non-emergent operations had an in-hospital mortality rate of 13.7% (p<0.01).
      Univariate analysis revealed among 39 preoperative and operative variables, age
      (years), age >70 years, remote myocardial infarction, cerebrovascular
      dysfunction, diabetes, preoperative renal failure, shock, cardiopulmonary bypass
      time (minutes), emergency operation as factors associated to in-hospital death
      (p<0.05). Stepwise logistic regression analysis selected as independent
      predicting variables (p<0.05), remote myocardial infarction (p=0.006),
      preoperative renal failure (p=0.032), shock (p=0.001), age >70 years (p=0.007).
      Finally, a probability table of death risk was obtained with the logistic
      regression coefficients. The lower death probability (10.6%) was calculated in
      absence of risk variables; the higher one in presence of all of them (79.7%).
      Between these extremes, a total of 64 combinations of death risk were obtained.
      CONCLUSIONS: Increasing age, shock, coronary artery disease and renal failure are
      variously associated to a high risk of in-hospital death after surgical
      correction of type A aortic dissection. This predictive model of death
      probability allows to collocate preoperatively patients with type A aortic
      dissection at different levels of risk for in-hospital death.

PMID- 11455291
TI  - A decade of experience with abdominal aortic aneurysm repair in octogenarians.
AB  - BACKGROUND: Should abdominal aortic aneurysms (AAA) be electively repaired in
      octogenarians? METHODS: This was a retrospective review of patients' charts over
      a ten-year period starting in January 1995. This study was conducted at St.
      Francis Hospital, Roslyn, New York, which is a tertiary referral center. All
      octogenarians who underwent AAA repair (elective and emergent) were included in
      this study (mean age 82.9 years). A total of 71 such patients were identified.
      Sixty-two patients had elective surgery and nine patients had emergent repair of
      the ruptured AAA. It was hypothesized before the study was conducted that AAA
      could be repaired in octogenarians with acceptable morbidity and mortality in an
      institution with vast experience in dealing with this disease. RESULTS: The mean
      aneurysm diameter was 6.73 cm. Twenty patients (28%) received bifurcated grafts,
      while 51 patients (72%) received tubular grafts. Four patients had coronary
      artery bypass graft before aneurysm surgery. Forty-four patients (62%) were male
      and 27 (38%) were female. The thirty day mortality rate after elective AAA repair
      was 1.4%, whereas after the repair of ruptured aneurysms was 44.4%. CONCLUSIONS:
      We concluded that the elective repair of abdominal aneurysms in most
      octogenarians is a safe and life-prolonging procedure if performed in an
      experienced tertiary center.

PMID- 11455292
TI  - Femoral vein valve repair with angioscopy-assisted anterior valve sinus
      plication. Early results.
AB  - BACKGROUND: The efficiency of angioscopy-assisted anterior valve sinus plication
      for primary deep venous insufficiency was evaluated. METHODS:  EXPERIMENTAL
      DESIGN: retrospective, clinical study with short follow-up. SETTING:
      institutional practice. PATIENTS: 15 limbs in 12 patients had class 4 or higher
      disease (SVS/ISCVS classification). Descending venography showed class 3 or 4
      reflux in all patients. Venous refilling time (VRT) was abnormal (<15 sec) in all
      of the nine limbs in which photoplethysmography was conducted. The limbs were
      treated with angioscopy-assisted anterior valve sinus plication of the
      superficial femoral vein. Postoperative descending venography was performed
      between the first and third day after operation. Clinical evaluation and VRT
      measurement were repeated when the patients were discharged and checked at the
      outpatient office. RESULTS: Mean follow-up was 22 weeks with a range of 1 to 70
      weeks. At postoperative descending venography, the reflux of the superficial
      femoral vein was significantly improved. At final follow-up, all patients
      reported greater or lesser relief of subjective symptoms. In four limbs with
      class 6 disease, ulcers healed and did not recur. In one limb with class 5
      disease, ulcers did not recur. In the other 10 limbs with class 4 disease, a
      distinct clinical improvement occurred with resolution of skin changes. VRT was
      normal in 11 of the 12 limbs examined. CONCLUSIONS: Our preliminary experience
      demonstrates that angioscopy-assisted anterior valve sinus plication gives early
      good clinical and hemodynamic improvement in patients with primary deep venous
      insufficiency.

PMID- 11455293
TI  - In vivo evaluation of ammonia plasma modified ePTFE grafts for small diameter
      blood vessels replacement. A preliminary report.
AB  - BACKGROUND: Today, saphenous veins are most frequently used to reconstruct
      occluded or diseased small diameter vessels (< or =6 mm in diameter). However,
      these veins are unavailable in 30-40% of patients. In such a situation,
      prosthetic grafts provide the only alternative. Since an endothelial cell (EC)
      lining, important for maintaining a haemostatic-thrombotic balance, does not
      develop onto the intima of implanted grafts in humans, these grafts occlude
      within a short period of time. The failure of vascular grafts is attributed to
      their characteristics which are nonconducive towards endothelial cell adhesion,
      spreading and growth. In order to examine whether the patency of vascular grafts
      can be improved by the surface modification of grafts' intima, small diameter
      grafts were modified by a novel ammonia plasma treatment to enhance their
      interactions with EC. METHODS: Through laparotomy, ammonia plasma treated ePTFE
      (4 mm in diameter) grafts (n=3) and control untreated grafts (n=6) were implanted
      into the distal infrarenal aorta of rabbits. At appropriate time, grafts and
      adherent tissue were removed, fixed, stained and embedded in Poly/Bed 812. Light
      microscopic examination of thin sections cut from the proximal and distal
      anastomatic and midportion segments of explanted grafts was carried out. RESULTS:
      In control group studies, all animals developed lower limb paraplegia within
      seven days of implantation. Light microscopic examination of explanted control
      grafts showed that control grafts were obstructed by thrombosis/intimal
      hyperplasia. However, ammonia plasma modified explanted grafts, after one month
      of transplantation, revealed an endothelial cell-like lining that covered the
      grafts' inner surfaces. Accordingly, these grafts remained patent in animals.
      CONCLUSIONS: The grafts' surfaces that are made conducive to EC adhesion and
      proliferation and host response may influence endothelial regeneration. It is
      hoped that the combination of angiogenic molecules (i.e. endothelial cell
      specific growth factors such as VEGF) with ammonia plasma modified grafts may
      provide further insight into the development of ideal small diameter prosthesis.

PMID- 11455294
TI  - Fibrin sealant coated stents compared with non-coated stents in a porcine carotid
      artery model. Preliminary study report.
AB  - BACKGROUND: Balloon expandable metal stents (BEMS) are used to treat restenosis
      following percutaneous transluminal angioplasty (PTA) and as primary treatment.
      Intimal proliferation (IP) and resultant restenosis occurs in 25-50% of patients
      despite all preventive measures. OBJECTIVE: to test the intra-arterial response
      to the insertion of a fibrin sealant (FS) coated BEMS vs an uncoated BEMS by
      measuring endothelization and IP. HYPOTHESIS: that a BEMS coated with FS will
      lead to rapid endothelization and prevent or reduce IP. RATIONALE: FS consists of
      fibrinogen and thrombin. Thrombin affects endothelial cell proliferation and
      reduces smooth muscle proliferation, the forerunner of IP and restenosis. Normal
      endothelium also releases substances that promote vascular relaxation and normal
      smooth muscle tone regulation. METHODS: Thirty-40 kg pigs (EA), Palmaz-Shatz BEMS
      (Cordis), FS Tissucol (Baxter Immuno). Stents were uniformly coated with FS in a
      special mold. Both coated and uncoated stents were mounted on balloon catheters
      and deployed caudad in the carotid arteries via an arteriotomy. Angiograms were
      obtained postdeployment. All specimens were examined grossly, photographed then
      fixed for histology and in some cases, scanning electron microscopy (SEM).
      RESULTS: Fifteen animals form this preliminary report. Sacrifice at five days as
      per original protocol showed insufficient stent incorporation. Thereafter 1/2 of
      the animals were sacrificed at 15 days and 1/2 at 30 days. PATENCY: coated
      stents: 6 patent, 9 thrombosed. UNCOATED: 7 patent, 8 thrombosed. Of five EA
      given postoperatively low molecular weight heparin (LMWH) 4 animals had patent
      stents 80%. HISTOLOGY: varying degrees of IP were seen in all specimens. In
      general the coated stents showed a greater degree than the uncoated. STENOSIS:
      presacrifice angiography revealed that where the stents were patent no stenosis
      was present, in fact, some demonstrated mild dilatation. This was particularly
      the case with the coated stents. CONCLUSIONS: Coating stents with FS is not
      detrimental. IP in these EA at 30 days did not produce stenosis. Postoperative
      LMWH appears helpful in maintaining patency in a thrombogenic experimental
      animal. Further study maintaining EA for 6-12 months should resolve whether the
      IP seen had achieved its maximum expression or would progress and produce
      stenosis.

PMID- 11455295
TI  - Upper extremity venous gangrene following coronary artery bypass. A case report
      and review of the literature.
AB  - Acute symptomatic upper extremity deep vein thrombosis (DVT) are estimated to
      account for only 2-4% of all deep vein thrombosis. Upper extremity DVT leading to
      phlegmasia cerulea dolens (PCD) occurs in an estimated 2-5% of these cases.
      Progression of PCD to venous gangrene is extremely rare with only 16 previously
      reported cases in the literature. Only 7 of the cited cases document significant
      tissue loss. This report describes a 61-year-old male who developed upper
      extremity DVT complicated by PCD which led to venous gangrene and limb loss.

PMID- 11455296
TI  - Flow cytometric analysis of DNA content and proliferation and immunohistochemical
      staining of Ki-67 in non-small cell lung cancer.
AB  - BACKGROUND: The aim of our study was to examine the significance of tumour DNA
      content and proliferation in lung cancer. METHODS: The DNA content and S-phase
      fraction (SPF) was determined by flow cytometry in 125 resected tumours of
      patients with non-small cell lung cancer. In 40 cases we compared the SPF with
      immunohistochemical staining of the Ki-67 protein using MIB-1 antibody. RESULTS:
      DNA aneuploidy was detected in 84.8% (106/125). Cell cycle analysis for the
      determination of proliferation activity was only possible in 69 (55.2%) cases. An
      SPF of 0-8% as a sign of low proliferation was found in 27 specimens. In advanced
      tumours at stage III and IV the proportion of tumours with SPF 9-16% was
      significantly (p<0.05) increased as compared to tumours at stage I and II. There
      was a significant correlation (p=0.012, ascent: 0.045) between SPF and MIB-1.
      Patients with aneuploid tumours had a relative risk of 1.4 to die earlier than
      patients with diploid tumours. Patients with SPF of 9-16% in the tumour tended to
      decreased survival (5-year survival rate: 29%) in correlation to patients with a
      percentage of SPF 0-8% (5-year survival rate: 38%, p=0.5). These differences were
      significant (p=0.048) in patients with adenocarcinomas only. In the multivariate
      COX-regression model age (p=0.03) and stage (p=0.0001) were significant
      prognostic factors, ploidy state (p=0.33) was of no prognostic significance.
      CONCLUSIONS: Flow cytometry seems to be a useful method for understanding the
      clinical behaviour of lung cancer. Especially the SPF in adenocarcinomas may be
      used as a prognostic indicator.

PMID- 11455297
TI  - Immunohistochemical study with antibody to glycoprotein GCDFP-15 for metastatic
      lung cancer from breast cancer.
AB  - Even when gross pathologic specimens are available, evaluation is always
      complicated due to the difficulty in distinguishing the pathologic diagnosis of
      an adenocarcinoma as a pulmonary metastasis of the breast or lung. In this paper,
      we describe the usefulness of a preoperative immunohistochemical study using
      gross cystic disease fluid protein-15 (GCDFP-15). A 50-year-old woman, who had
      undergone a right radical mastectomy due to an infiltrating ductal carcinoma 4
      years previously, was admitted because of an abnormal shadow on chest
      roentgenography. A chest CT scan showed a nodule 20 mm in diameter with an
      irregular margin and vascular involvement in the S3 region of the right lung.
      Though the specimen from a percutaneous CT guided needle biopsy revealed
      characteristic pathologic findings of a primary lung adenocarcinoma under H.E.
      stain, which was recommended for lobar resection, we re-examined that specimen
      immunohistochemically, which disclosed that the tumor cells were negative for the
      antibody to pulmonary surfactant apoprotein and were positive for GCDFP-15
      antibody. Therefore, the diagnosis of a metastatic breast carcinoma in the lung
      was established. Upon her request, a wedge resection of the right upper lobe
      including the tumor was performed under video-assisted thoracoscopic surgery
      (VATS). Her postoperative course was uneventful.

PMID- 11455298
TI  - Hydatid cyst fistula into the aorta presenting with massive hemoptysis. Case
      report and literature review.
AB  - Hydatid involvement of the aorta is extremely uncommon. We present a case where a
      hydatid cyst of the lung eroded into the thoracic aorta, causing massive
      hemoptysis. Successful repair was performed by resection (including left lower
      lobectomy) and graft interposition.

PMID- 11455299
TI  - The Rumel technique for lateral thoracotomy closure.
AB  - The closure of the commonly used lateral thoracotomy incision usually includes
      pericostal sutures which encircle the ribs. Risks of these pericostal sutures
      include the injury and/or the entrapment of the intercostal neurovascular bundle
      located along the inferior underedge of each rib. The simple adaptation of the
      Rumel tourniquet technique is described as an aid for the primary closure of a
      lateral thoracotomy which may avoid some of the potential complications inherent
      to thoracotomy incisions.

PMID- 11455300
TI  - About concomitant abdominal aortic aneurysm and other surgical diseases.

PMID- 11455301
TI  - About management of infected grafts.

PMID- 11455302
TI  - [Home care services and the role of "caregivers"].
AB  - The care of children and adolescents with cancer continues to grow in complexity.
      While in most cases we are winning the fight, now quality of life (QoL) is
      becoming a problem to face and a challenge. Pediatric total care policy includes
      also home care to deliver in any stage of the disease. This can become very
      useful in the terminal stage, when QoL is the primary goal. The WHO has defined
      palliative care as integrating the psychologic and spiritual aspects of patient
      care; affirming life, and regarding dying as a normal process; neither hastening
      nor postponing death, offering a support system to help patients live as actively
      as possible until death; and offering a support system to help the family cope
      during the patient's illness and their own bereavement&. Recently this aim is
      considered also for children. The home care team is usually composed by a
      physician responsible, few physicians, several nurses, social workers,
      psychologists plus the family/home caregiver. In most countries health
      professionals now rely on family/home caregivers, who can play an important role
      in the team. The American College of Physicians has recently edited useful
      Guidelines. The Penn State Milton S. Hershey Medical Center suggests four key
      ideas which make the word COPE in order to succeed in solving problems: C for
      Creativity, O for Optimism, P for Planning, E for Expert information. Not
      everywhere in Europe home care is included as a part of the Health Care System,
      even if there are increasing pressures from shrinking budgets. As hospitals can
      be upsetting for the child, is hospital care always necessary during the long
      course of the disease? Home care, when feasible, can be an alternative approach.
      Strong motivations support pediatric home care. The life rhythms are better
      preserved if the whole family is at home. Parents must be taught how to cope and
      how to talk with their children, the sick one and his/her siblings. The dialogue
      is easier at home. Home care respects the needs of siblings. Adjustment to living
      is easier at home, taking into consideration the active help of relatives and
      close friends. Children need stability and honesty. Pain is a source of great
      distress for children. When possible pain control must be obtained or at least
      tried at home. The child may find a better comfort when in his own bedroom and,
      if he feels better, he can play at home. When the child is dying the treatment is
      focused for a good QoL and no more on cure: children can feel the change. The
      difference is impressive if the child is followed at home and not only in
      hospital. Volunteer Groups can help the child's family better at home then in
      hospital. Also in Italy Scientific Pediatric Societies, health care professionals
      together with Parents' Associations could push politicians and implement the
      integration of several types of services for treatment of children, including
      home care, offering their collaboration in the global therapy design.

PMID- 11455303
TI  - Electromyographic and manometric anorectal evaluation in children affected by
      neuropathic bladder secondary to myelomeningocele.
AB  - BACKGROUND: Fecal incontinence, with or without persistent constipation is often
      underestimated in children affected by spina bifida. Medullar lesions to the L-S
      metameres result in a slowing of rectal and/or rectal-sigmoid motility, loss of
      anal or rectal sensation, deranged external anal sphincter function, altered
      motility of the anal levator muscles, and loss of motor coordination of the
      internal sphincter. We conducted an electromyographic and electromanometric
      evaluation of the anorectal tract in a group of children affected by
      myelomeningocele (MMC) in an attempt to evaluate the degree of functional damage
      and to provide appropriate treatment. METHODS: Anorectal manometry was conducted
      in 83 children affected by MMC (2-16 yrs, mean age: 8.4 yrs); surface
      electromyography was also performed in 37 of these children. We thus evaluated
      overall sphincter pressure, the inhibitory anal reflex, the rectal sphincteric
      reflex and rectal motility during stimulation and at rest. Recording perfusion
      catheters (0.1 ml/sec) were placed at rectal and anal level; rectal stimulation
      was conducted with an endorectal balloon. RESULTS: In all patients there was a
      reduction in overall sphincter pressure (15-25 mmHg; n.v. 45+/-25 mmHg) and the
      functional length of the anal canal (1-1.8 cm) compared with age matched
      controls. The inhibitory anal reflex was normal in all patients, although its
      amplitude, duration and sensitivity were not constant. Similar findings were
      obtained for the rectal-sphincteric reflex. The rectal sigmoid motility results
      were difficult to interpret: sudden, fast and high pressure waves of peristaltic
      progression were followed by prolonged pauses. No correlation was found between
      urodynamic and anorectal manometric data. Treatment consisted in daily emptying
      of the rectum so as to avoid fecal retention. Fifteen patients, who presented
      prolapse and sphincteric hypotonia ( </=10 mmHg), underwent cerclage by 2/0
      prolene, with sustained good RESULTS. CONCLUSIONS: While evaluation parameters of
      the neuropathic bladder are well standardised, data on the neuropathic rectum are
      contradictory. Moreover, the results of functional examination are not always an
      aid to treatment strategy. Therefore, further studies are required to establish
      an appropriate diagnostic-therapeutic protocol.

PMID- 11455304
TI  - [Food intakes in breast-feeding mothers].
AB  - BACKGROUND: The relation between mother's diet and breastmilk composition is
      still an open issue. Nutritional inadequacies during lactation may affect the
      well-being of both the mother and the infant. For this reason breast feeding
      women usually pay attention about their alimentary practices and about their
      style of life during breast-feeding period. This research was conducted to verify
      the adequacy of lactating mother's diet in comparison with the Italian
      recommended daily assumption levels of nutrients (LARN 1996) for this category.
      We have also compared food intake of not breast feeding mothers with the LARN,
      and analyzed the differences between these groups of mothers. METHODS: Forty
      eight healthy infants were selected, 23 bottle fed, 25 breast fed. Mothers's diet
      in the previous 48 hours was investigated using a structured questionnaire. The
      data collected were processed using software Dietosystem to obtain the daily
      nutrient intakes. RESULTS: The wetnurses's diet in comparison with the LARN 1996
      resulted hypocaloric and hyperproteic, deficient in Calcium, Iron, folic acid and
      vitamin E. Surprisingly not breast feeding mothers's intake of nutrients is
      closer to LARN levels than that of breast feeding mothers. CONCLUSIONS: Mothers
      are not informed enough about their alimentation during lactating period.
      Pediatricians must improve their knowledge about this subject and give the
      mothers the information they need to achieve the recommended food requirements.

PMID- 11455305
TI  - [Nutritional status disorders prevalence rates in a sample of pediatric oncology
      Day Hospital patients].
AB  - BACKGROUND: Nutritional status is more important in children than in adults
      because it is necessary to support normal growth and development. In
      industrialized countries the prevalence of nutritional status disorders in the
      pediatric population are as follows: 35-40% of children are overweight/obese,
      while the underweight status disappeared in some reports or, when it is present,
      it is associated with other diseases. The aim of this study was to investigate
      the prevalence rates of nutritional status disorders among an unselected sample
      of Pediatric Oncology Day Hospital patients. METHODS: Anthropometric parameters
      of weight and height have been measured in patients affected with solid tumor
      either on-therapy or off-therapy (0-24 mo). Then Real Body Weight (% RBW) was
      estimated referring to National Center for Health Statistic percentiles. The
      sample was then divided into 4 weight classes (under-weight, normal-weight, over
      weight and obese) according to % RBW. RESULTS: Overweight patients (overweight +
      obese) were 44.4%, and 13.9% underweight. Dividing the patients according to
      whether they are on-therapy or off-therapy, the prevalence of overweight was
      36.9% in the former group and 52.9% in the latter, and the underweight prevalence
      was 26.3 vs 0%. CONCLUSIONS: Our preliminary data show that in this sample of
      patients on treatment obesity and overweight are present in a similar percentage
      of the healthy population, but underweight status prevalence is 26.3%. In the
      sample of patients off-therapy the underweight status disappeared while the
      overweight status increased. These data suggest that nutritional assessment in
      oncologic patients is required in order to provide nutritional strategies.

PMID- 11455306
TI  - Exposure to violence and victimization and the use of violence by adolescents in
      the United States.
AB  - Violence by adolescents in the United States is of growing concern. Despite a
      decrease in the rate of violence and death by firearms, firearm injuries are the
      second leading cause of death among Americans age 15 to 24 and the third leading
      cause of death among 10- to 14-year-old children. Although there are many factors
      associated with the use of violence by youths, exposure to violence and
      victimization has consistently been a predictor of the use of violence, as well
      as intentions to use violence, carrying a gun, and having attitudes accepting of
      the use of violence and aggressive behavior to resolve conflict. Adolescents'
      families, friends, neighborhoods, schools, and the media provide sources of
      exposure and victimization related to the use of violence. The cultural
      transmission of deviant behavior theory establishes a framework for understanding
      the influence of exposure to violence and victimization from these sources on
      adolescents' use of violence.

PMID- 11455307
TI  - Transgenic foods, pesticides, dioxin, passive smoke. Consequences on breast milk.
AB  - In recent years the efforts of companies manufacturing cow milk (CM) formulas
      have led to the development and availability of special formulas, which have
      dramatically reduced the morbidity of infants with food allergy (FA). However,
      the safety of several infants and children with food allergy is put to a severe
      test by transgenic foods, pesticides, and dioxin entering the scenario, also
      provoking breast milk contamination. Regarding transgenic foods, it is
      significant the attitude taken against people attempting to call them
      Frankenstein food, whereas pesticides and dioxin present in dietary foods for
      infants and young children, after a first arising of alarmed and inflamed
      controversies, have almost fallen into oblivion. Several of these substances are
      able to trigger immune alterations. Recent reports have shown that pears can
      contain pesticides in 54% of cases, a finding which obliges us to review
      elimination diets devised for allergic babies. However, these foods are far from
      being ideal both from the nutritional adequacy and hypoallergenicity; moreover,
      passive smoke is now a genetic factor. We would like to stress, according to the
      Latin wisdom that stands on the portal of our Clinic in puero homo, which means.
      In infant is the seed of the future man, that our goal is not only to reduce
      morbidity and mortality, but mainly to insure the best quality of life both to
      infants and adults.

PMID- 11455308
TI  - [Preadolescence and suicide attempts].
AB  - The authors refer their experience regarding suicide attempts in preadolescence,
      an age less discussed than adolescence in the international literature on the
      subject. A case-study of 27 patients (12 boys and 15 girls), all under 13 years
      and in-patients in the Child Neuropsychiatry Section of the Department of
      Pediatric and Adolescence Sciences of the Turin University during ten years (1990
      1999), is described. Various criteria are taken into consideration, including
      incidence peaks, social extraction, birth order, methods used, psychiatric
      illness in the family, family break-ups, organic illness in the family,
      experience of loss, previous signs of emotional disturbance, precipitant events,
      any repeat attempts and the patients' psychopathological profiles, and the most
      important aspects are illustrated. The data resulting from the case-study show
      that suicide attempts by pre-teenagers are not as rare as commonly believed,
      especially at the age just before entering into true adolescence. The authors
      conclude by emphasising that suicide attempts seem to be a phenomenon involving
      particularly less well-off classes (a good 87% of the case-study); among the
      methods used, the ingestion of drugs is the most common, the incidence of
      psychiatric illness in the family (45%) is certainly relevant and in 70% of cases
      there were previous and evident signs of emotional disturbance. In consideration
      of the information already available and the findings reported in this study,
      attempted suicide attempts appear to be a <<symptom>> and not a pathology, at
      which basis different psychopathological profiles can be found: it is a symptom
      of a serious emotional and relational problem, which rarely reveals itself
      suddenly and even more rarely is resolved without help.

PMID- 11455309
TI  - Sleep apnea and respiratory dysfunction in congenital myotonic dystrophy.
AB  - A case of neonatal Myotonic Dystrophy (MD) is presented. A 35 week old 3570 g
      baby was born to a mother affected by MD and pregnancy-induced unstable diabetes.
      Soon after birth, he developed apnea, severe hypoglycemia, hypocalcemia,
      hypotonia and mild respiratory distress. His clinical course improved during the
      following days, but persistent episodes of desaturation and/or cyanosis did not
      subside; hypotonia was mild. A polysomnographic recording showed mixed central
      and obstructive apnea. DNA testing showed trinucleotide repeat expansion
      mutations diagnostic of MD. The baby was discharged with home-sleep monitoring
      and breast-feeding. Recurrent apnea/bradycardia was the main clinical feature in
      this case of congenital MD, with increased risk of an acute life-threatening
      event.

PMID- 11455310
TI  - [Beginning and early development of pediatric hospitals].

PMID- 11455311
TI  - [Effectiveness of oral supplements of folates, vitamins B12 and B6 in
      hemodialysed patients. Preliminary results after 5 months of follow-up].
AB  - BACKGROUND: Elevated serum levels of homocysteine have increasingly been
      associated as a risk factor of cardiovascular disease. Recent reports
      demonstrated that supplements of folates, vitamin B12 (B12) and vitamin B6 (B6)
      are effective in correcting serum Hcy levels in hemodialysed patients. AIM: to
      assess the effectiveness of oral supplements of folates, B12 and B6, in order to
      reduce serum Hcy levels in our cohort of hemodialysed patients. METHODS: Sixty
      one hemodialysed patients have been enrolled in the study (age 68+/-13 years;
      hemodialysis 62+/-42 months). Oral supplements of calcium folinate (30 mg 3 times
      a week), B12 (500 mg 3 times a week) and B6 (200 mg 3 times a week) were
      administered at the end of each hemodialysis session. Serum levels of Hcy, folic
      acid and B12 were tested at the beginning of the study and at 2 month intervals.
      RESULTS: After 5 months of follow-up, serum levels of Hcy were normalised in 19%
      of our patients and in total 70% of them showed a reduction >8% when compared
      with the basal Hcy levels. No side effects related to folates, B12 or B6
      supplementation were observed. CONCLUSIONS: Oral supplements of folates, B12 and
      B6 are a safe and effective treatment of hyperhomocysteinemia in hemodialysed
      patients.

PMID- 11455312
TI  - [Microbiological evaluation of two different disinfection protocols of a new
      hemodialysis monitor with an ultrafilter].
AB  - BACKGROUND: Hemodialysis monitors represent a frequent site for bacterial
      contamination. METHODS: Two different disinfection protocols on a new device
      (Formula(R), Bellco) have been compared: only chemical or chemical plus heat
      disinfection by means of CFU, and LAL test. The endotoxin removing capacity of
      ultrafilter was tested with varying lipopolysaccharide concentrations. RESULTS:
      Similar results were obtained with heat disinfection compared to chemical
      disinfection (CFU and LAL test). The LAL test (chromogenic and gel-clot) showed
      that the ultrafilter performance decreased with use and was significant after 200
      operating hours. CONCLUSIONS: Heat disinfection between dialysis shifts and
      chemical disinfection at the end of the day exclude bacterial contamination of
      the monitor as well as chemical disinfection; LAL test is a useful and simple
      tool to assess the ultrafilters performance in each Center.

PMID- 11455313
TI  - [Percutaneous renal biopsy with a semi-automate device].
AB  - BACKGROUND: The percutaneous renal biopsy is a fundamental investigation in the
      diagnostic procedure for renal diseases. The introduction of the kidney
      localisation by real-time ultrasounds made the procedure more effective and safe.
      The use of semi-automated and automated biopsy devices seems to go in the same
      way. METHODS: In this paper a retrospective investigation is made on 118 renal
      biopsies performed at our Nephrology Unit from 1990 to 1999 with the semi
      automated device Biopty Bard and with direct ultrasounds guidance. The number of
      post-biopsy complications have been evaluated. RESULTS: Any major complications
      (as surgical interventions and deaths) have been observed. The number of minor
      complications was low and in agreement with the literature data (post-biopsy
      macrohematuria = 6.8%, hemoglobin loss =/>20% = 0.8%, hematoma = 5.1%, lumbar
      pain 0.8%). The 98.4% of renal biopsies were diagnostic and 91.4% had a number of
      glomeruli =/>5. CONCLUSIONS: The automated ultrasound-guided procedure is a
      feasible and reliable technique for percutaneous renal biopsy. It gives a greater
      yield of diagnostic tissue without increasing the rate of clinical complications,
      even in Nephrology Units, such as ours, that perform a small number of biopsies
      every years.

PMID- 11455314
TI  - [Scabies in a dalysis unit. Mystery and prejudice].
AB  - BACKGROUND: Pruritus is one of the most common symptoms of uremia. The etiology
      of uremic pruritus is steel incompletely known. Scabies may be a cause of itching
      in these patients. METHODS: Retrospective analysis of beginning and developing of
      a scabies outbreak in a Dialysis Unit with 160 patients. RESULTS: Sixteen cases
      of scabies were observed in the Dialysis Unit from April 1998 and January 1999:
      in 6 of them the scarification was positive. In 10 the scarification was
      negative, but itching disappeared after treatment with benzyl benzoate 20%. Many
      courses were necessary (max 6). Prophylaxis (treatment with benzyl benzoate 20%
      for 3 days and lingery cleaning) was applied to approximately 400 people. No
      cases were observed among health care workers of the Dialysis Unit. CONCLUSIONS:
      In a Dialysis Unit the diagnosis of scabies is difficult because the patients
      often have generalized itching; moreover some of them are affected by neuropathy
      that may make the infestation of scabies more difficult to identify. The most
      important factor to limitate the outbreak seems to be the prophylaxis of people
      who take care of patients (health-care workers, family members and car-drivers).
      It seems also necessary to repeat the treatments many times. The most exposed
      patients seemed to be those with diminished independence, diabetes and
      malnutrition.

PMID- 11455315
TI  - [The status of peritoneal dialysis in Piedmont by 12/31/1997].
AB  - BACKGROUND: The aim of the study is to examine the situation of chronic uremia
      substitutive treatment by means of peritoneal dialysis in Piedmont on December
      31, 1997 using data from the Piedmont regional dialysis and transplant register.
      METHODS: Starting from the year 1981, data are reported (absolute, per million
      population, and according to different patient's anagraphic ages) about
      peritoneal dialysis prevalence and incidence; about basic nephropathies; drop-out
      from treatment; patient's rehabilitation; complications incidence, particularly
      peritonitis; patient's survival compared with survival of patients treated,
      during the same years with extracorporeal techniques. RESULTS: The data
      demonstrate, during these years, an increase of peritoneal dialysis incidence and
      prevalence; patients' survival curves, compared with those of patients treated
      with extracorporeal techniques, are very similar during the first years of
      treatment and worse afterwards, but never reaching statistical significance.
      CONCLUSIONS: They support Peritoneal Dialysis as a very good kind of substitutive
      treatment for some years, but this opinion deserves further examination and
      investigation on a longer period of time.

PMID- 11455316
TI  - [Biopsy experience at the G. Bosco Hospital from 1996 to 1999].
AB  - BACKGROUND: Aim of this study was a retrospective analysis of the renal biopsies
      performed in our Division. METHODS: Since January 1, 1996 to September 30, 1999
      289 biopsies were performed on native kidneys, 90 patients were older than 65.
      RESULTS: The most frequent nephropathy was IgA glomerulonephritis (IgAGN) (28%),
      followed by membranous glomerulonephritis (MGN) (11%). In patients older than 65,
      the most frequent was MGN (20%), followed by IgAGN (12.2%). The total
      complications were 84 (29.1%) (hematomas >3 cm 1%; blood transfusion: 1.4%).
      Complications were not related to age, blood pressure, renal function, clinical
      presentation, number of shots. In 217 patients, the results obtained with two
      different modalities were compared: manual system (needle size=15 gauge) and
      automatic system (18 gauge). No statistically significant differences were found
      as regards the number of shots for single biopsy, number of glomeruli and major
      complications (1.6% vs 1.3%), while minor complications were more frequent in the
      second group. CONCLUSIONS: In conclusion, the number of renal biopsies performed
      in our Division has been increasing year after year. This trend can be partially
      explained by our wider indications to renal biopsy in elderly population (the
      data related to resident population showed the greatest prevalence of biopsies in
      patients 70 to 79 years old). Renal biopsy actually represents a safe examination
      even in elderly patients. From a technical point of view, on the basis of
      personal experience, 18 gauge acecut automatic needles seem to be preferred to
      other kind of devices.

PMID- 11455317
TI  - [Data from the Aosta Valley dialysis and transplant regional registry].
AB  - BACKGROUND: The need of collecting data concerning uremic local population
      requested by EDTA registry and, more recently, by the Italian dialysis and
      transplant registry (RIDT) has led different Italian regions to organize
      structures able to give such clinical and epidemiological informations. METHODS:
      In Aosta Valley (where live nearly 120.000 people) a data collection has been
      activated since 1981 on paper support and since 1995 (with data from December
      1994) on computer registry. If compared to more experienced Italian structures,
      such as Piedmont and Lombardy regional registries, RDTVA has the advantage of
      receiving data from a unique Dialysis centre (composed by a hospital area and a
      limited care centre). RESULTS: During these years, according to what happened in
      the rest of Italy, in Aosta Valley the uremic population increased with a per
      million population (pmp) rate prevalence from 125 patients in 1981 to almost 1000
      in 1998. Also the incidence showed a similar trend, with 110 patients/pmp in 1981
      82 and 160 in 1997. The gross mortality rate concerning years 1995-98 was about
      12%, the main death causes being cardiovascular events (60%), similarly to
      national data. CONCLUSIONS: Even with the limits deriving from small numbers,
      RDTVA, because of its favourable position, can play the role of epidemiological
      observatory for uremic diseases and contribute to future health policy.

PMID- 11455318
TI  - [The significance of "atypical metaplasia" in the follow-up of patients operated
      for bladder cancer].
AB  - BACKGROUND: The aim of this study was to evaluate the clinical usefulness of
      urinary cytology in the follow-up of patients who under-went surgery for bladder
      cancer. Particularly, the positive predictive value of urinary cytology and time
      elapsed between a positive test and the diagnosis of a cystoscopically confirmed
      bladder tumor are analyzed. METHODS: This study was carried out at the
      Cytological Laboratory Department of Experimental Medicine and Pathology,
      University La Sapienza, Rome. Among 230 cases studied since 1996, 30 male
      patients over 50 were examined (25 with a previous bladder cancer and 5 with a
      previous prostate cancer) with long time follow-up, who underwent more than two
      cytological examinations on voided urine (2-12) at pre-fixed intervals. RESULTS:
      Nine (30%) of the patients suffered from recurrent disease. The cytological
      examinations was positive in 8 out of the 9 positive cases and negative in 17 out
      of the 21 negative cases. Absence of disease was confirmed in all the latter
      cases both by cystoscopic examination and clinical follow-up. One negative case
      showed clearly malignant cells in more than one specimen taken at different time
      intervals. This patient is actually under strict control. In 5 cases atypical
      metaplasia was present in the cytological specimen. In two of those cases
      cystoscopic examination 5 and 8 months later confirmed progressive disease. In
      the other three cases cystoscopy showed no evidence of disease. Two of the
      patients are well and alive after 2 and 14 months respectively. One is dead of
      prostatic cancer. CONCLUSIONS: Considering the cases of atypical metaplasi as
      positive the cytological examinations showed 100% sensibility, 81% specificity, a
      predictive negative value of 1 and a predictive positive value of 0.66.

PMID- 11455319
TI  - [Cryptohypospadias: Surgical approach and long-term results].
AB  - BACKGROUND: Chordee without hypospadias is a rare morphological abnormality of
      the penis capable of interfering with sexual function. Usually, cases of chordee
      without hypospadias require surgical correction, and the aim of this study is to
      assess the efficacy of the techniques normally used in this pathology. METHODS:
      The authors analyze the surgical outcomes achieved in 34 patients presenting
      various degrees of ventral or lateral curvature of the erect penis and operated
      on in our department over the past 22 years. Twenty-nine subjects attended for
      follow-up, including 13 who have now reached adulthood. RESULTS: The milder forms
      of chordee without hypospadias (Horton and Devine type III and lateral deviations
      of the penis) all benefited from minor surgery (dermal grafts and Nesbit dorsal
      plication of the contralateral penile tunica albuginea) and were corrected with a
      single operation. The most serious forms of chordee without hypospadias where the
      hypoplasia variously affected the corpus spongiosum, Buck's fascia and the dartos
      fascia (Horton and Devine types I and II), were submitted to a supplementary
      extensive urethral mobilization or occasionally a urethroplasty and one-third of
      them presented persistent residual curvature. CONCLUSIONS: The authors advocate a
      more aggressive surgical approach (urethroplasty and/or patches on the ventral
      tunica albuginea as an alternative to urethral mobilisation) in subjects with
      more pronounced defects.

PMID- 11455320
TI  - [Optimization of extracorporeal dialytic treatment: on-line hemodiafiltration].
AB  - The study evaluates the potential of high ultrafiltration on-line
      hemodialfiltration (HDF) as a means of achieving the goals of extracorporeal RDT:
      the removal of small and medium-sized molecules, vascular stability and
      biocompatibility. The removal of small molecules was correlated with the UF rate
      and therefore with reinfusate volume. Medium-sized molecules were only removed
      from high permeability synthetic membranes in HD, but to a greater extent in HDF
      because of higher absorption. Vascular stability during the dialytic session is
      improved by convective processes, as is confirmed by a low prevalence of arterial
      hypertension in HDF patients. This suggests that HDF facilitates the achievement
      of dry body weight and therefore an improved correction of hydrosaline retention
      which is the main cause of hypertension in RDT patients. The biocompatibility of
      the dialytic system depends on the membrane and the dialysate. Synthetic
      membranes were shown to be much less toxic than cellulosic membranes and
      ultrapure dialysate was a useful aid to reduce the risk of inflammatory stimuli.
      On-line HDF associated the value of low-cost sterile dialysate-reinfu sate with a
      highly efficient and well tolerated technique.

PMID- 11455321
TI  - [Neonatal chronic kidney failure associated with cyclo-oxygenase-2 inhibitors
      administered during pregnancy].
AB  - Non-steroidal anti-inflammatory drugs (NSAID) are used since years as tocolytic
      due to their capacity to inhibit cyclo-oxygenase (COX) expressed in uterus and
      fetal membranes, fundamental for labour initiation and maintenance. The use of
      nimesulide, a COX-2 selective NSAID, has been recently proposed due to its
      capacity to selectively inhibit the enzyme expressed in the myometrium and
      endometrium. A case of neonatal irreversible end stage renal failure after
      maternal assumption of nimesulide as tocolytic for 6 week is reported. Cesarean
      section at the 32nd week due to oligohydramnios gave birth to a baby girl of 2090
      g, in good general conditions, without signs of respiratory distress and of
      visible abnormalities. From birth she displayed oligo-anuria which required
      dialytic substitutive therapy from the second day of life. At US scan both
      kidneys had normal diameters for gestational age slightly increased echogenicity
      and a reduced cortico-medullary differentiation. On the 20th day of life she had
      a surgical renal biopsy for the persistence of oligo-anuria, showing fetal
      glomeruli, without lymphocytic interstitial infiltrate, and normal tubuli without
      evidence of necrosis. She is now 16 months old and under automated peritoneal
      dialysis on a home dialysis program. The occurrence of chronic renal failure in
      strict relationship with maternal nimesulide assumption in this case is strongly
      suggestive for a pharmacological damage, either direct or mediated by renin
      angiotensin inhibition, and possibly modulated by genetic factors, likely to
      account for the different outcome of similarly treated patients. A cautious use
      of this drug as long term tocolytic should be recommended while waiting for ad
      hoc experimental and clinical evidences of safeness.

PMID- 11455322
TI  - Editorial.

PMID- 11455323
TI  - From the Art Director's Desk.

PMID- 11455324
TI  - Melatonin and aging. A brief survey.
AB  - The relationship between the pineal gland and aging has been assumed already
      nearly a century ago. Recently, melatonin was considered by some authors as a
      "wonder drug." The present paper tries to summarize the relationship between
      melatonin and aging in three points. 1. Decline of melatonin production during
      aging. 2. The role of the pineal gland in the regulation of the ovarian cycle in
      aged females. 3. The antioxydant effect of melatonin and aging. The age-related
      decline of pineal melatonin production is due to the degenerative changes of the
      neural structures (serotonergic and noradrenergic neuron systems) innervating the
      pineal gland and the suprachiasmatic nuclei rather than to the degeneration of
      the pineal tissue itself. The decreased melatonin production of the pineal gland
      preceds the destruction of ovarian cyclicity which can be partly counteracted by
      melatonin or by 5-hydroxytryptophane administration. The antioxydant effect of
      melatonin might explain its lifespan-prolonging effect, at least to a certain
      degree.

PMID- 11455325
TI  - Testosterone levels and bone mineral density in young healthy men and in young
      infertile patients.
AB  - OBJECTIVES. Although relatively little information exists concerning bone mineral
      density (BMD) in men, it has been demonstrated that similarly to observations in
      women, BMD decreases also with age in men, although to a smaller extent, and
      osteoporosis is increasingly recognized. Most reports concentrate, however, on
      men of advanced age. Therefore, we decided to investigate BMD in young healthy
      volunteers and in young patients suffering from infertility, and to compare it
      with serum tes-tosterone levels. MATERIAL AND METHODS. The study was performed on
      80 men divided into two groups. The first group consisted of 39 young healthy men
      (mean age 22.1+/-0.3 years; range 20-29). The second group consisted of 41
      infertile men with oligozoospermia (mean age 28.0+/-0.5 years; range 23-34).
      Serum testosterone levels and BMD were measured in each subject. RESULTS.
      Decrease in BMD (T-score below -0.3) was observed in 35.9% of the subjects in the
      group of young healthy men and in 60.9% of the subjects in the group of infertile
      patients. Among these numbers -penia (T-score between -1 and -2.5) was found in 4
      subjects (10.3%) in the group of young healthy men and in 13 subjects (31.7%) in
      the group of infertile patients. There was a positive correlation between
      testosterone concentrations and BMD as well as T-score both in healthy subjects
      and in infertile patients. CONCLUSION. Results of the present study indicate that
      attention should be paid to testosterone deficiency in the young age in terms of
      the potential risk of decreased bone mineral density in the advanced age.

PMID- 11455326
TI  - Evidence of pineal endocrine hypofunction in autistic children.
AB  - OBJECTIVE: The pineal hormone melatonin (MLT) has been proven to play a
      fundamental physiological regulatory role on both biological and psychic
      functions and alterations of the light/dark circadian rhythm of MLT have been
      described in several chronic immunoinflammatory diseases and in psychic
      disorders. Aim of the present biological explanatory study was the evaluation of
      MLT circadian rhythm in autistic children, in order to preliminary assess the
      pineal endocrine function in the autistic syndrome. METHODS: The study included
      14 children suffering from classical infantile autism, who were investigated for
      the whole 24-hour circadian rhythm by collecting venous blood samples at 4-hour
      intervals. Serum levels of MLT were measured by the RIA method. The control group
      consisted of 20 age-matched healthy children. RESULTS: No autistic patient showed
      a normal MLT circadian rhythm. Moreover, autistic children showed significantly
      lower mean concentrations of MLT, mainly during the dark phase of the day, with
      respect to the values observed in the controls. CONCLUSION: The results of this
      preliminary study suggest the existence of a pineal endocrine hypofunction in
      autistic children, whose pathophysiological significance needs to be thoroughly
      investigated in successive clinical studies.

PMID- 11455327
TI  - Influence of hypovolemic and hypertonic treatments on plasma vasopressin levels
      and fluid balance in the thyroidectomy-induced hypothyroid rats.
AB  - OBJECTIVES: This study was undertaken to investigate the effects of hypovolemic
      and hypertonic treatments on plasma vasopressin (AVP) levels and fluid balance in
      thyroidectomy-induced hypothyroidism in the rat. The influence of hypothyroidism
      on AVP responsiveness to hypertonic and hypovolemic stimuli were compared.
      MATERIALS & METHODS: Adult male rats were divided into two groups. The rats were
      surgically thyroidectomized (hypothyroid) or sham-operated (euthyroid). Two weeks
      later these groups were further divided in three subgroups each containing six
      rats. The first subgroup consisted of unchallenged rats. The second group
      underwent hypovolemic treatment by using I.P. 700 mg polyethylene glycol. The
      third subgroup consisted of hypertonic (1.5 M NaCl; 1 ml/100 g) stimulated
      animals. All rats were decapitated and trunk blood collected in heparinized
      tubes. Plasma samples were stored at -20 degrees C until assayed. Plasma AVP, T3
      and T4 levels were measured by radioimmunoassay. Hematocrit values and plasma Na
      and K concentrations were also determined. RESULTS: In the hypothyroid rats,
      hypovolemic treatment significantly reduced the expected increases in plasma AVP
      levels (p<0.05) compared to the respective intact animals. In the hypertonic
      group, similar increases occurred in plasma AVP levels of hypothyroid and
      euthyroid rats. Hematocrit values and plasma Na concentrations were not
      significantly different in the hypothyroid rats compared to euthyroid rats.
      CONCLUSION: In conclusion, thyroidectomy-induced hypothyroidism may affect AVP
      response to hypovolemic stimulus although it has no important effect on basal AVP
      levels nor AVP response to hypertonic stimulus.

PMID- 11455328
TI  - The human body circadian: How the biologic clock influences sleep and emotion.
AB  - Diurnal, nocturnal or seasonal modes of behavior are not passive responses to
      changes in the environment; rather, they are generated by an endogenous circadian
      pacemaker, entrained by a few environmental cues like lightdark cycles. Circadian
      clock mechanisms involve periodic gene expression, synchronized by a
      hierarchically superior structure located in mammals in the hypothalamic
      suprachiasmatic nuclei. Cycles of sleep and wakefulness are the most conspicuous
      circadian rhythm. Since modern humans use artificial light to extend their period
      of wakefulness and activity into the evening hours, they adhere to a shortnight
      sleep schedule with a highly consolidated and efficient sleep. As shown by
      studies in artificial long nights, modern humans may be sleepdeprived. Humans
      have also increasingly insulated themselves from the natural cycles of light and
      darkness. Still, the human circadian pacemaker has conserved a capacity to detect
      seasonal changes in day length. A mood disorder involving a recurring autumn or
      winter depression (seasonal affective disorder, SAD) is related to latitude, with
      the number of cases increasing with distance from the equator. SAD is ameliorated
      by using brilliant light. In nonseasonal depression, mood typically fluctuates
      daily, with improvement over the course of the day, and various physiological
      functions exhibit an altered circadian pattern, suggesting a link with circadian
      disruption. Treatment of circadian rhythm disorders, whether precipitated by
      intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or
      by extrinsic factors (e.g., jet lag, shift work) has led to the development of a
      new type of agents called "chronobiotics," among which melatonin is the
      prototype.

PMID- 11455329
TI  - Melatonin treatment stabilizes chronobiologic and cognitive symptoms in
      Alzheimer's disease.
AB  - OBJECTIVES: A retrospective study on the efficacy of melatonin in treatment of
      sleep and cognitive disorders of Alzheimer's disease was conducted. METHODS:
      Fourteen patients (8 females, 6 males), mean +/- S.D. age 72 +/- 9 years were
      included. All patients received 9 mg gelatin melatonin capsules p.o. daily at
      bedtime for 22 to 35 months. Overall quality of sleep was assessed from sleep
      logs filled in by the patients or their caretakers. Neuropsychological evaluation
      was performed by Functional Assessment Tool For Alzheimer's Disease (FAST), Mini
      Mental, Alzheimer's Disease Assessment Scale (ADAS), and Mattis' and Blessed's
      scales. At diagnosis, all patients had cognitive and neuroimaging alterations
      (cortical and bitemporal atrophy) compatible with different evolutionary stages
      of the disease. RESULTS: At the time of assessment, a significant improvement of
      sleep quality was found in all cases examined. There were no significant
      differences between initial and present evaluation in scores of FAST, Mini
      Mental, and ADAS, and of Mattis' and Blessed's scales. Clinically, the patients
      exhibited lack of progression of the cognitive and behavioral signs of the
      disease during the time they received melatonin. Sundowning was no longer
      detectable in 12 patients and persisted, although attenuated, in 2 patients.
      CONCLUSION. The results suggest that melatonin can be useful for treatment of
      Alzheimer's disease.

PMID- 11455330
TI  - Effects of growth hormone (GH) and growth hormone releasing hormone (GHRH) on
      progesterone and estradiol release from cultured rat granulosa cells.
AB  - OBJECTIVES: It has been reported that GHRH-GH-IGF-1 system plays an important
      role in the regulation of ovarian follicular development and maturation. METHODS:
      In order to evaluate the direct effects of growth hormone releasing hormone
      (GHRH) and growth hormone (GH) on steroidogenesis, the effects of GHRH and GH on
      progesterone and estradiol release from cultured rat granulosa cells were
      examined. The progesterone and estradiol in supernatants were measured with RIA
      methods. RESULTS: Our results demonstrated that the addition of GH to the culture
      medium produced a marked stimulation of progesterone and estradiol. The
      stimulating effects were observed after administration of GH in all
      concentrations: 1, 10, 100 nM during 60 and 120 mins of incubation. During 240
      mins of incubation the minimal stimulation of progesterone and estradiol was
      found. However, GHRH administered in 1, 10 and 100 nM did not change progesterone
      and estradiol release from cultured granulosa cells. CONCLUSION: Growth hormone
      (GH) but not GHRH has direct stimulating effects on progesterone release from
      cultured rat granulosa cells.

PMID- 11455331
TI  - Effect of 24, 25-dihydroxycholecalciferol on the placental immunoreactive
      calcitonin.
AB  - OBJECTIVES: Calcitonin (CT) has a regulative function in calcium (Ca) transfer
      from mother to the fetus. There are indications that cholecalciferol can play a
      role in this process. With this background, the effect of 24, 25
      dihydroxycholecalciferol (24, 25-DHC) on immunoreactive CT by human placenta at
      term was studied in vitro. METHODS: Placental tissue samples were incubated in
      culture medium with normal total Ca (1.3 mM) concentrations during 6 hours at 37
      degrees C. 24, 25-DHC was added to the samples. RESULTS: Addition of 24, 25-DHC
      in concentrations of 25, 75 and 150 pg/ml was followed by a significant decrease
      of CT levels in medium. The concentrations decreased from 100% (basis value after
      2 hours) to 31%, 46% and 49% respectively. CONCLUSION: Probably 24, 25-DHC has a
      modulating effect on the regulation of placental Ca transfer by CT.

PMID- 11455332
TI  - Pyrimidine and purine salvage deoxyribonucleoside metabolism in hepatic and renal
      homogenates from rats pretreated with propylthiouracil or L-thyroxine.
AB  - OBJECTIVES: In vitro activities of thymidine kinase (TK, EC 2.7.1.21), adenosine
      kinase (AK, EC 2.7.1.20) and deoxycytidine kinase (dCK, EC 2.7.1.74) enzymes
      involved in the salvage pathway of DNA precursor synthesis, in homogenates of the
      rat liver and kidney, were examined. Type I iodothyronine-5'-deiodinase (5'D-I)
      is the main enzyme responsible for peripheral metabolism of thyroid hormones.
      This occurs especially in the liver, kidney and muscle. The activity of 5'D-I is
      inhibited bypropylthiouracil (PTU), an antithyroid drug. METHODS: The liver and
      kidney were collected from rats pretreated in vivo with either a 0.1% solution of
      PTU in drinking water for 2 weeks or injected with levothyroxine (L-T(4), 50
      &mgr;g/kg BW, daily) for 2 weeks. The enzyme activities were measured by
      ascending chromatography and expressed asthe amounts of radioactive reaction
      products of the phosphorylation of dThd (for TK), ofdAdo (for AK and dCK) and of
      dGuo (for dCK). RESULTS: In liver homogenates, PTU-pretreatment decreased the
      activities of the three enzymes when compared to control values and those of L
      T(4)-treated animals; also L-T(4) injections decreased the AK and dCK activities
      in the liver homogenates. PTU-pretreatment increased TK activity and the rate of
      dGuo phosphorylation in kidney homogenates, when compared to controls and to the
      L-T(4)-pretreated animals. Conversely, both PTU- and L-T(4)-pretreatment reduced
      the rate of dAdo phosphorylation in kidney homogenates. CONCLUSION: Changes in
      the activities of examined enzymes which participate inpyrimidine orpurine
      metabolism of the salvage pathway of DNA synthesis in the liver afterPTU
      pretreatment (as shown herein) are similar to the changes of the 5'D-I activity
      after PTU-treatment (as reported by others). Thus, the observations suggest a
      role of the salvage pathway of DNA synthesis in the peripheral metabolism of
      thyroid hormones.

PMID- 11455333
TI  - FROM TEN YEARS AGO: Health in the 21st century-a change in belief systems.

PMID- 11455334
TI  - Circasemicentennial Season's Appreciations.

PMID- 11455335
TI  - Editorial: "Savoir pour prevoir, Prevoir pour prevenir" 

PMID- 11455336
TI  - From the Art Director's Desk.

PMID- 11455337
TI  - Music medicine. A neurobiological approach. 
AB  - Music medicine is a relatively new medical specialty for most countries in the
      world and a rediscovery of a discipline for some countries in Europe. In the
      scope of music medicine are health problems of musicians like stage fright and
      psychic stress, pain syndromes and motor disturbances. Specific demands of
      musicianship like performing before the public, performing under the constant
      critical scrutiny of conductors, being expected to perform perfectly, and the
      physical demands of performing on a musical instrument were seen as the
      determinants of the complaints, and treatment does usually not differ between
      musicians and non-musicians with comparable diseases. In the present article,
      growing neurobiological evidence will be summarized showing that musicians differ
      from non-musicians on brain structure and function and on some hormonal and
      immunological parameters. Musicians tend to have atypical brain organization for
      verbal and non-verbal materials, their auditory system tracks sound levels more
      accurately, musicians attend pre-consciously to musical material and they react
      to music as if it is a stressor, i.e. with increased activity of the autonomic
      nervous system and with an increase in stress hormone production. A musician is
      more likely than a non-musician to be non-righthanded and to be vulnerable to
      atopic diseases. Testosterone levels are assumed to be lower (male) and higher
      (female) than controls. Melatonin was found to be elevated, and ACTH was related
      to musical talent. His/her brain reflects early music practice by enlarged
      structures, like the anterior part of the corpus callosum and the representation
      for piano tones and for the left thumb and little finger in string players. In
      addition, the left planum temporale was found to be larger in musicians with
      absolute pitch. These differences between musicians and non-musicians may have
      implications for music medicine in theory and practice, and further research
      should help to improve treatment of musicians.

PMID- 11455338
TI  - Serum melatonin circadian profile in women suffering from the genital tract
      cancers.
AB  - OBJECTIVES: Although there is increasing evidence that the pineal gland may play
      a role in human malignancy, the studies on melatonin concentrations in different
      types of malignant tumors brought about controversial results. However, changes
      in melatonin concentrations have been observed in some types of human malignant
      tumors. Therefore we decided to study the circadian melatonin rhythm in patients
      suffering from malignant tumors of the female genital tract, and to compare them
      with subjects free from neoplastic disease (healthy volunteers and patients with
      myomatous uterus). MATERIAL AND METHODS: A total of 46 women were analyzed in
      this study. The subjects were divided into 3 groups. The first group consisted of
      23 patients with malignant tumors of the genital tract (mean age 50.3+/-2.2
      years; mean+/-SEM, range 32-77 years). The second group consisted of 16 healthy
      volunteers (mean age 50.9+/-1.8 years; mean+/-SEM, range 42-63) who served as the
      first control group, whereas the third group consisted of 7 subjects who suffered
      from myomatous uterus (mean age 45.7+/-2.3 years; mean+/-SEM, range 39-56) and
      served as the second control group without malignancy. Blood samples were
      collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00 and
      08:00 h. Melatonin concentration was measured using RIA kit. RESULTS: There were
      no significant differences in circadian melatonin profiles among the three groups
      studied. Taking into consideration the type of tumor of the genital tract,
      significantly lower melatonin secretion has been found in patients with
      endometrial cancer in comparison with tumor-free control groups, whereas no
      significant differences in melatonin secretion have been observed between tumor
      free control groups and patients with invasive ovarian cancer and squamous
      cervical cancer. However, significant differences have been observed between
      endometrial cancer and invasive ovarian cancer. CONCLUSION: Its seems probable
      that melatonin concentrations in human malignancy may, at least partly, depend on
      hormone dependency of the particular type of tumor.

PMID- 11455339
TI  - Delta opioid modulation of hypothalamic serotonergic neurotransmission in the
      ovariectomized and steroid-primed rat.
AB  - OBJECTIVES: We have investigated the modulating effects of DPDPE (a delta opioid
      agonist) and opioid receptor antagonists on both LH release and indoleamine
      concentrations in specific hypothalamic regions of the ovx and steroid-primed
      rat. METHODS: DPDPE was intracerebroventricularly infused alone or with either
      ICI 154129 (a delta opioid antagonist) or naloxone under ketamine anesthesia.
      Blood samples were collected at hourly intervals on the afternoon of the
      anticipated LH surge. The rats were then decapitated and the medial preoptic area
      (MPOA), suprachiasmatic nucleus (SCN), median eminence (ME) and arcuate nucleus
      (ARN) surgically isolated by micropunch. Concentrations of 5-HT and its
      metabolite (5-HIAA) in these samples were determined by HPLC with ECD. Plasma LH
      levels were measured by RIA. RESULTS: The delta-agonist significantly reduced 5
      HT concentrations in the SCN, ME and ARN, but not in the MPOA. 5-HIAA levels were
      decreased, but these changes were significant in only the MPOA and ARN compared
      to the control group. ICI 154129 had no significant effects on 5-HT release and
      turnover in any of the hypothalamic regions examined. However, co-administration
      of DPDPE with naloxone resulted in significant increases in 5-HT and 5-HIAA
      concentrations in the MPOA, SCN, ME and ARN compared to the DPDPE-treated group.
      Plasma LH levels were either low or undetectable in all groups. CONCLUSIONS: The
      present results suggest that delta-opioid receptors are involved in the opioid
      inhibition of the serotonergic neurotransmission in the hypothalamus. It is
      thought that the ketamine anesthesia interfered with LH secretory systems.

PMID- 11455340
TI  - Effect of somatostatin analog-octreotide on the adjuvant arthritis in rat.
AB  - OBJECTIVES: The aim of present study was the estimation of the anti-inflammatory
      effects of the somatostatin analog-octreotide in the adjuvant arthritis in rats.
      MATERIAL AND METHODS: The arthritis was induced by intradermal injection of
      Freund's adjuvant at the foot's pulvinar of the posterior paw in August's strain
      rats. The animals received: 0.9% NaCl, octreotide (oct), dexamethasone (dx) and
      oct together with dx. The clinical signs, body weight, weight of spleens and
      thymuses were estimated. The cellularity of the thymus was evaluated by computer
      assisted morphometry and levels of IL-1 beta in serum were measured by the ELISA
      method. RESULTS: In the rats treated with oct in comparison to the untreated
      group the reduction of the clinical signs, a decrease of the body weight fall,
      inhibition of the thymus weight fall, the lower spleen's weight, an increase of
      the thymus cellularity and an increase of the IL-1 beta level in serum were
      found. The rats treated with dx showed greater to oct-treatment reduction of the
      clinical signs and greater loss of the thymus weight. The spleen's weight was
      similar to the healthy group. A significant reduction of the thymus cellularity
      and a decrease of the IL-1 beta level were also found. The rats treated with dx
      and oct jointly showed in comparison with dx alone a weaker reduction of the
      clinical signs, lower thymus weight fall, an increase of the IL-1 beta level in
      serum, without the significant influence on the other parameters. CONCLUSION: The
      octreotide shows the anti-inflammatory effect in adjuvant arthritis, but it is
      weaker in comparison to dexamethasone. Treatment with dx and oct together does
      not result in the more pronounced anti-inflammatory action of glucocorticoid
      alone.

PMID- 11455341
TI  - Diffuse neuroendocrine system and mitochondrial diseases: molecular and cellular
      bases of pathogenesis, new approaches to diagnosis and therapy. 
AB  - Structural and functional alterations of mitochondria have been shown to be
      responsible for a wide variety of clinical disorders that are referred to as
      "mitochondrial diseases." It is now obvious that many factors are involved in
      transport of mitochondrial proteins including cytokines, chaperones, chemokines,
      neurosteroids, ubiquitin and many others. At the same time the participation and
      the role of biogenic amines and peptide hormones (which are produced by the
      diffuse neuroendocrine system cells located in different organs) in endogenous
      mechanisms of mitochondrial diseases are still unknown. Taking into account the
      wide spectrum of biological effects of biogenic amines and peptide hormones, and
      especially their regulatory role for intercellular communication, it seems
      important to analyze the possible participation of these molecules in the
      pathogenesis of mitochondrial disorders as well as to draw up new ways for
      elaboration of new markers for lifetime diagnosis, definition of prognosis and
      efficiency of specific therapy in neurodegenerative diseases.

PMID- 11455342
TI  - Relationships of climatic data to immune and hematologic variables in normal
      human.
AB  - OBJECTIVES: The purpose of this study was to examine the relationships between
      climatic and immune or hematologic variables in the peripheral blood of normal
      human. METHODS: Twenty-six normal volunteers gave blood samples monthly during
      one calendar year for flow cytometric assays of peripheral blood mononuclear
      cells (PBMC) and assays of red blood cell (RBC)- and platelet-related variables.
      Time relationships between the weather and immune or hematologic variables were
      investigated by means of multiple regression and bivariate cosinor analyses.
      RESULTS: Highly significant relationships were found among number and percentage
      of neutrophils, lymphocytes, CD4+, CD8+, CD25+ (interleukin-2-receptor bearing
      lymphocytes), CD20+ B lymphocytes, number of platelets and RBC, hemoglobin (Hb),
      mean corpuscular (MC) volume, MC Hb, MC Hb concentration, mean platelet volume or
      plasma fibrinogen levels and ambient temperature, sunlight duration, air
      pressure, wind speed, relative humidity, and rainfall duration/day. An important
      part of the variability in the immune and hematologic variables could be
      explained by the composite effects of contemporaneous and lagged climatic
      variables. Common seasonal rhythms were detected in the time series of the above
      immune/hematologic and sun insolation variables, such as ambient temperature.
      CONCLUSIONS: The results suggest that i) short-term fluctuations in atmospheric
      activity modulate immune and hematologic features in the peripheral blood of
      normal human; and ii) the seasonal rhythms observed in immune/hematologic
      variables may be entrained by the seasonal rhythms in ambient temperature.

PMID- 11455343
TI  - Effects of somatostatin analogs octreotide and lanreotide on the proliferation
      and apoptosis in colon 38 tumor: interaction with 5-fluorouracil.
AB  - OBJECTIVES: The aim of this study was to compare the effects of two somatostatin
      (SS) analogs: octreotide and lanreotide administered separately or together with
      5-fluorouracil (5-FU) with the action of 5-FU alone, on proliferation, apoptosis,
      proliferation/apoptosis (P/A) ratio and tumor weight in the murine transplantable
      Colon 38 cancer. MATERIALS AND METHODS: Two separate experiments were performed
      on male mice of B6D2F1 strain. In both experiments the animals were implanted
      subcutaneously with suspension of Colon 38 cancer cells. A few days later, in the
      first experiment, octreotide was given once daily for six days at the dose of 10
      &mgr;g/animal and in the second experiment a single dose of lanreotide (1
      mg/animal) was administered. 5-FU was treated once (in the first experiment) or
      twice (in the second experiment) at the dose of 70 mg/kg b.w. depending on the
      duration of the experiment. In both experiments the incorporation of
      bromodeoxyuridine into the tumor cell nuclei was used as an index of cell
      proliferation (labeling index - LI). The labeling of nuclear DNA fragmentation
      according to TUNEL method was considered as an index of apoptosis (AI). RESULTS:
      It has been found that both SS analogs, given separately, significantly decreased
      LI of tumor cells, increased their AI and decreased P/A ratio of Colon 38 tumors,
      as compared to controls. 5-FU given alone (in both experiments) significantly
      enhanced AI, decreased P/A ratio, but did not significantly change LI, as
      compared to controls. The joint treatment with 5-FU and each of the two SS
      analogs did not produce any additive effects either on proliferation or
      apoptosis. The tumor weight was significantly decreased only by the joint
      treatment with 5-FU and octreotide, as compared to the control group.

PMID- 11455345
TI  - Editorial: "We stay on the intellectual shoulders of the giants of medicine from
      past days."

PMID- 11455344
TI  - Hurdles to asepsis, universal literacy, and chronobiology-all to be overcome.
AB  - A joining of chronobiology and endocrinology was achieved in 1974 at a symposium
      focusing on the critical role of the hypothalamic-pituitary-adrenal network on
      the basic side and on the first drug to carry timing in its name. The next step
      is a section on chronobiology in this neuroendocrinology journal. An account of
      the problems encountered before both asepsis and universal literacy became the
      law of the profession and of the land serves here as background to endeavors in
      behalf of chronobiologic literacy. A step toward the latter goal is the use of
      systematically collected measurements of heart rate and blood pressure evaluated
      by computer against reference standards from peers of corresponding age, gender
      and ethnicity. Thereby, an illustrative, clinically relevant aspect of everyday
      physiology is resolved within the otherwise neglected normal range, and disease
      risk syndromes are detected so that preventive treatment can be instituted before
      catastrophic disease occurs. The scope of this chronobiology section of the
      Neuroendocrinology Letters is to map the time-qualified feedsideward interactions
      within the neuroendocrines, in the rest of an organism and in the environment.
      Thereby, we replace time-unqualified feedbacks and feedforwards, along imaginary
      axes, by neuroendocrine and cellular networks operating predictably insofar as
      rhythmically within the range of everyday physiology. Subtle effects are thus
      found that are otherwise covered by the curtain of ignorance drawn over the
      normal range. More important, feedsidewards account for opposite effects that
      recur rhythmically, and thus help clarify mechanisms that may underlie the
      difference between stimulating or inhibiting a malignancy and thus shortening or
      lengthening the lifespan.

PMID- 11455346
TI  - From the Art Director's Desk.

PMID- 11455347
TI  - Letter to the Editor. Claude Bernard was right: hormones may be produced by "non
      endocrine" cells.

PMID- 11455348
TI  - The mediating role of cutaneous sensitivity within neonatal
      psychoneuroimmunology.
AB  - Preliminary results of this study have been presented at the ICIS Conferences
      held in Atlanta, 1998; a Summary of results has been quoted in Adamson-Macedo
      (1997; 1998). OBJECTIVES: Despite knowledge that preterm infants in intensive
      care are in distress and need to be provided with appropriate intervention,
      studies with ventilated babies are still rare particularly during their first
      weeks of life. This study tested the hypothesis that cutaneous stimulation in the
      form of TAC-TIC therapy, involving only light stroking and NOT massage or
      kinesthetic massage, has a mediating role in eliciting beneficial
      psychoneuroimmunological coactions in the ventilated preterm during the first
      week of post-natal life. METHODS: A repeated measure, counterbalanced design, was
      used to collect data twice daily for three consecutive days. This intervention
      was compared with a control condition consisting of a period of spontaneous
      activity during which the same infants lay alone with no intervention taking
      place. For the first time, monitoring facilities were made available for
      immunological, physiological and behavioral responses to be assessed
      simultaneously before and after intervention and before and after spontaneous
      activities. RESULTS. A one tailed t-test indicated that the cutaneous
      intervention resulted in significantly more episodes of beneficial coactions than
      matched sessions of spontaneous activity. CONCLUSION: It is suggested that the
      sensory nerves endings in the skin receive the stimulation from the stroking
      actions; consequently impulses are being sent via afferent nerve fibers to the
      limbic system where the sensation is interpreted, by 68% of the neonates, as
      being comforting or not distressing.

PMID- 11455349
TI  - Comparative quantitative ultrastructural study of pinealocytes in eight mammalian
      species.
AB  - OBJECTIVES: The studies related to quantitative ultrastructural features of
      mammalian pinealocytes, especially in comparative aspects, are relatively rare.
      Quantitative ultrastructural studies in many mammalian species are lacking.
      Because of the existence of differences in diurnal melatonin profiles in various
      species it seemed interesting to compare the ultrastructure of pinealocytes in
      various mammalian species, both laboratory and domestic animals. MATERIAL AND
      METHODS: The pineal glands of the following mammalian species have been examined:
      mouse, rat, Syrian hamster, gerbil, sheep, horse, pig and European bison. For
      each species 4 adult animals (2 males and 2 females) were used. Cross-sectional
      areas of the pinealocyte and its nucleus and the relative volumes of the
      following cytoplasmic organelles were analyzed: mitochondria, lysosomes, Golgi
      apparatus, granular endoplasmic reticulum, and lipid droplets. The relative
      volumes of membrane-bound bodies (MBB) in the pig pinealocytes, pigment granules
      in the horse pinealocytes, and calcareous concretions in the gerbil pineal gland
      were also analyzed. In addition, numerical density of dense-core vesicles and
      "synaptic" ribbons was estimated. RESULTS: Ultrastructure of pinealocytes in
      examined species shows many common features, and existing differences are of
      quantitative nature only. The observed qualitative differences include MBB in the
      pig, abundance of pigment granules in the horse, and calcareous concretions in
      the gerbil. Relative volumes or the numbers of some cell structures
      (mitochondria, Golgi apparatus, lipid droplets, dense-core vesicles and
      "synaptic" ribbons) show distinct interspecie differences, whereas those of other
      cell structures (granular endoplasmic reticulum, lysosomes) are similar in all
      studied species. CONCLUSIONS: The ultrastructural features of pinealocytes in all
      examined species confirm earlier suggestions of high activity of these cells. No
      distinct correlation has been found between the type of melatonin secretion and
      ultrastructural patterns of pinealocytes. It should be stressed, however, that
      the ultrastructure of pinealocytes in the present study was studied during the
      daytime, whereas differences in melatonin secretion are observed at night.

PMID- 11455350
TI  - Influence of radiotherapy on 6-sulphatoxymelatonin levels in the urine of brain
      cancer patients.
AB  - OBJECTIVES: The synthesis of melatonin, an endogenous compound synthesized by the
      pineal gland in the brain, is reported to be depressed in patients with primary
      cancers of the breast, prostate, stomach and rectum. It is not known whether
      patients with brain cancer exhibit altered melatonin synthesis. Also unknown is
      whether radiotherapy given to the region of the brain where the pineal gland is
      located affects the synthesis of melatonin. This information could be relevant to
      the clinician for the successful treatment of brain cancer patients since
      melatonin has been reported to be a potent oncostatic agent. METHODS: Urinary
      levels of 6-sulphatoxymelatonin, the chief metabolite of melatonin, are routinely
      used as an index of pineal melatonin production and secretion. In this study, the
      concentrations of 6-sulphatoxymelatonin (aMT6S) excreted in the urine before and
      during radiotherapy of patients with primary or metastatic brain cancer were
      determined and compared with the values obtained in breast or lung cancer
      patients who also received radiotherapy (excluding exposure of the brain where
      the pineal gland is located). RESULTS: The results showed a wide variation in the
      mean concentration of aMT6S excreted in the urine. CONCLUSION: The data from this
      preliminary study suggested that radiotherapy given to the region of human brain,
      where the pineal gland is located, does not significantly affect the excretion of
      aMT6S, the chief metabolite of melatonin.

PMID- 11455351
TI  - The opposite effect of morning or afternoon application of melatonin on collagen
      accumulation in the sponge-induced granuloma.
AB  - OBJECTIVES: Collagen accumulation in the sponge-induced granuloma is under
      inhibitory influence of melatonin. This effect was observed when the pineal
      hormone was injected late in the afternoon. DESIGN: The present study was
      conducted to compare the afternoon and morning melatonin application and to
      answer the question whether melatonin effect on the collagen accumulation in
      wounds is dependent on tissue circadian sensitivity to the pineal hormone.
      METHODS: In order to induce granulation tissue development, the Ivalon sponge was
      implanted subcutaneously in the Wistar rats. Then the animals were divided into 5
      groups: intact controls, rats injected with vehicle in the morning or in the late
      afternoon, as well as animals receiving melatonin (30 &mgr;g/100g body wt) in the
      morning or late afternoon. After 4 weeks, the sponges were removed for the
      analysis of both soluble and total collagen content. Collagen was analyzed as
      hydroxyproline content in the tissue. Insoluble collagen was calculated. RESULTS:
      The afternoon application of melatonin was seen to decrease the total and
      insoluble collagen content in the sponge-induced granuloma (p<0.05). However,
      morning administration of the pineal hormone increased collagen capacity in the
      granulation tissue (p<0.01). CONCLUSION: Therefore, contradictory effect of
      morning or afternoon melatonin application on the collagen content in the
      granulation tissue has been shown. This phenomenon is supposed to be due to
      various circadian sensitivity of tissues to melatonin and may suggest that the
      mechanism of melatonin regulatory action on collagen accumulation in wounds is
      complex.

PMID- 11455352
TI  - Neonatal Psychoneuroimmunology: Emergence, Scope and Perspectives.
AB  - Interdisciplinary Neonatology investigates and cares for at-risk babies,
      including risk for developmental disabilities. Psychoneuroimmunology seeks to
      unravel relationships amongst behavioural, neural, endocrine, and immune
      processes, and their mutual role in maintaining health and treating disease. This
      article presents an integrative approach to the emergence, scope and perspectives
      of a new sub-discipline, i.e. Developmental Neonatal Psychoneuroimmunology. The
      Equilibrium Model (ThEM) proposed by Adamson-Macedo (1991) will be used as a way
      of representing coactions; within this frame, Gottlieb's experiential
      canalization (1991b) contributes an explanation of how the
      psychoneuroimmunological development of the preterm neonate can be facilitated.

PMID- 11455353
TI  - Hemangiosarcoma of the Thyroid Gland. A case report. 
AB  - OBJECTIVES: The authors described a case of rare histological type of primary
      thyroid tumor-angiosarcoma. Angiosarcoma generally represents a rare connective
      tissue tumor in the head and neck region. Its biological behavior is locally
      aggressive and destructive with a high recurrence rate. METHODS: A case of a rare
      histological type of primary thyroid tumor -angiosarcoma-has been described
      including fine needle aspiration biopsy, histology, and autopsy. RESULTS:
      Irrespective of the complex approach the angiosarcoma of the patient referred to
      was diagnosed in a radically inoperative stage of the disease. Radiation was
      therefore applied after the tumor mass was diminished with the partial
      thyroidectomy and a correct histopathological diagnosis was rendered.
      Nevertheless, the locally destructive course was followed with a rather rapid
      spread of the tumor (lymph nodes, bones, lungs, and brain). Autopsy proved with
      certainty that the thyroid was the primary tumor location. A suspected kidney
      origin due to an uncertain sonography shadow of this region was excluded with a
      complete absence of any neoplastic spread of the angiosarcoma in the abdominal
      cavity at all.

PMID- 11455354
TI  - Complementarity is a useful concept for consciousness studies. A Reminder.
AB  - We describe the concept of complementarity and argue that it is a useful concept
      for consciousness and other studies at the interface of conscious phenomena and
      physical reality. After outlining the history and source of the concept within
      psychology, we describe its place as a working hypothesis for the mind-brain
      problem. We then point out that generalized quantum non-locality could be of
      importance even for macroscopic objects. If this is so, complementarity would be
      the key-concept to understand EPR-like correlated systems.

PMID- 11455355
TI  - Cross-spectrally coherent ~10.5- and 21-year biological and physical cycles,
      magnetic storms and myocardial infarctions*
AB  - Magnetic storms trigger myocardial infarctions with mechanisms relating to heart
      rate variability. Solar cycle-to-solar cycle differences and solar cycle stage
      dependence shown herein may resolve prior controversy and serve to advocate
      coordinated worldwide systematically aligned biological and physical monitoring.
      * This paper was originally invited by the historian-geophysicist Wilfried
      SCHRoDER of Bremen, Germany, for his biographical "Encounters," and is to serve
      as an update on the project on the BIOsphere and the Cosmos (BIOCOS) and its
      offspring ICEHRV (Dr. Kuniaki Otsuka's International Chronome Ecologic Study of
      Heart Rate Variability). It is intended for distribution at a NATO conference on
      space weather hazards, organized by Dr. Ioannis Daglis, June 18-29, 2000.

PMID- 11455356
TI  - Editorial: The visible is not the only truth, nor is it the whole truth.

PMID- 11455357
TI  - From the Art Director's Desk.

PMID- 11455358
TI  - INVITED GUEST EDITORIAL: Ten ontogenetic theses for promotion of health and
      primary prevention of important diseases by a prenatal and early postnatal
      neuroendocrineimmune prophylaxis*
AB  - * These theses were partly presented at a Parliamentary Evening on "Environment
      and Health" in Berlin, January 19, 2000.

PMID- 11455359
TI  - FSH beta-subunit gene expression in long-term ovariectomized rat after pulsatile
      intracerebroventricular microinjections of GnRH.
AB  - OBJECTIVES: The purpose of this study was to examine whether in long-term
      ovariectomized rats direct pulsatile intracerebroventricular microinfusions of
      GnRH would result in frequency dependent biosynthesis of pituitary FSH beta
      subunit mRNA. METHODS: Stainless steel cannula was stereotaxically implanted into
      the third ventricle of ovariectomized rats. 1 nM of GnRH microinjections were
      given at frequency 1, 2, 4 pulses/hour during 5 hours. Pituitary FSH beta-subunit
      mRNA level was determined by Northern-blot and serum FSH concentration was
      examined by RIA. RESULTS: Exogenous GnRH (1nM) induced a significant increase of
      pituitary content of FSH beta-subunit mRNA when administered 30 or 60 min
      intervals over 5 hours to ovariectomized rats. RESULTS: GnRH microinjections
      given at frequency of 1 pulse/hour were mostly effective resulting both in 85%
      increase of FSH beta-subunit mRNA level as compared to control as well as a
      significant (78%) stimulation of FSH release. CONCLUSIONS: our data show that in
      a long term ovariectomized rats (without steroid and gonadal peptides
      supplementation) a direct pulsatile intracerebroventricular microinjections of
      GnRH induce frequency-dependent pituitary FSH beta-subunit mRNA biosynthesis in
      the same mode as it was reported for gonadectomized and steroid replaced rats. It
      seems therefore that this method would represent an interesting alternative to
      the use of classical agents to disconnect, in vivo, the pituitary from
      hypothalamic GnRH influence. It may also provide a physiological data concerning
      regulatory aspects of gonadotropin subunits biosynthesis.

PMID- 11455360
TI  - The effect of continuous darkness and illumination on the function and the
      morphology of the pineal gland in the domestic pig. Part I: The effect on plasma
      melatonin level.
AB  - OBJECTIVES: Results of the majority of studies have revealed that diurnal changes
      in circulating melatonin level in the domestic pig differ from the typical
      patterns observed in other species. The aim of the present investigation was to
      study the effect of continuous darkness and continuous illumination on plasma
      melatonin in the pig. MATERIAL AND METHODS: The study was performed on three
      groups of immature gilts. The first group was kept under 14hrs light:10hrs dark
      cycle (500 lx of fluorescent light during photophase), the second group-under
      continuous illumination (500 lx of fluorescent light) and the third group-under
      red light with intensity below 1 lx, which was considered as darkness. The pigs
      were maintained nine days under above reported conditions and then plasma
      melatonin was monitored during five consecutive days. RESULTS: The diurnal
      changes in plasma melatonin concentration with increased levels during
      scotophases were observed in gilts kept under light:dark cycle, but these changes
      were characterized by low regularity and repeatability. In pigs kept under
      continuous darkness the circadian changes in plasma melatonin with the highest
      levels during natural nights were found. No significant circadian changes in
      plasma melatonin were noted in gilts exposed to continuous illumination.
      CONCLUSIONS: The obtained results suggest that the diurnal rhythm of melatonin
      secretion in the domestic pig is generated endogenously and entrained by
      environmental light. The present results supported also the previously reported
      observations showing low regularity of diurnal changes in circulating melatonin
      in the pig.

PMID- 11455361
TI  - The effect of continuous darkness and illumination on the function and the
      morphology of the pineal gland in the domestic pig. Part II: The effect on
      pinealocyte ultrastructure.
AB  - OBJECTIVES: The characteristic feature of the pig pinealocytes is the presence of
      numerous membrane bounded bodies (MBB), which according to our previous results
      may be involved in the secretory activity. The present study was undertaken to
      analyze the effect of continuous darkness and illumination on the ultrastructure
      of the pig pinealocytes. MATERIAL AND METHODS: The study was performed on three
      groups of gilts. The first group (control) was kept under a cycle of 14hrs light
      (500 lx) and 10hrs dark per day. The second group was exposed to continuous
      illumination (500 lx). The third group was kept under red light with intensity
      less than 1 lx, which was considered as darkness. The pigs were kept for 14 days
      under above reported conditions and then slaughtered at 08:00. The point count
      analysis was used in quantitative studies of pinealocyte substructures. RESULTS:
      The exposition of pigs to continuous illumination resulted in the decrease in the
      relative volume of mitochondria and in the numerical density of multivesicular
      bodies as well as in the increase in the relative volume of MBB in pinealocyte
      cell bodies. The exposition to continuous darkness led to the increase in the
      relative volume of mitochondria and the numerical density of dense core vesicles
      as well as induced some changes in smooth endoplasmic reticulum in pinealocyte
      cell bodies. CONCLUSIONS: The obtained results point to mitochondria, MBB,
      multivesicular bodies, dense core vesicles and smooth endoplasmic reticulum as
      the structures of the pig pinealocyte, which are controlled by environmental
      light conditions.

PMID- 11455362
TI  - Melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary
      gonadal axis in the rat.
AB  - OBJECTIVES: We have investigated the changes in serum luteinizing hormone (LH),
      follicle stimulating hormone (FSH) and testosterone levels together with
      testicular histology in both pinealectomized (PNX) and intact rats. MATERIAL and
      METHODS: Twenty-one animals were PNX and allowed to recover for two months. Group
      I was assigned as PNX, group II PNX+melatonin and group III PNX+Human Chorionic
      Gonadotropin (HCG). Rats in group IV were sham PNX (S-PNX). An intact group of
      animals was s.c. injected with melatonin (0.5 mg/kg/day), another group with a
      combination of melatonin+HCG (5000 IU/kg/day) for seven days. Controls received
      saline alone (1 ml/kg). At the end, all animals were decapitated and blood
      samples obtained. Serum LH and FSH levels were determined by Radioimmunoassay,
      testosterone values by Chemiluminescent Enzyme Immunassay. Testicular tissue was
      collected and processed for light microscopy. RESULTS: Serum LH levels were
      increased following PNX, but no such increases were seen in testosterone. In the
      PNX+melatonin group, serum LH and testosterone values were found to be similar to
      those of S-PNX group. HCG supplementation to PNX rats resulted in significant
      decreases in LH (p<0.005), but increased testosterone levels (p<0.001). Melatonin
      administration to intact animals significantly decreased both LH and testosterone
      levels (p<0.01). Co-administration of HCG+melatonin resulted in significant
      decreases in LH (p<0.001) and increases in testosterone levels (p<0.01). Serum
      FSH values did not show significant changes among groups. Only HCG administration
      significantly reduced FSH levels (p<0.01). CONCLUSIONS: Our results suggest that
      melatonin inhibits testosterone secretion by acting at hypothalamo-pituitary
      axis. There is a functional relationship and feedback regulation between the
      pineal gland and the testes.

PMID- 11455363
TI  - Unconscious Imagery in Painting.

PMID- 11455364
TI  - Melatonin prevents oxidative damage to protein and lipid induced by ascorbate
      Fe(3+)-EDTA: Comparison with glutathione and alpha-tocopherol.
AB  - OBJECTIVES: The ability of melatonin to protect protein and lipid against
      oxidative damage induced by an ascorbate-Fe(3+)-EDTA (AFE) system which generates
      the hydroxyl radical was investigated using bovine serum albumin (BSA) and
      phosphatidylcholine (PC) liposomes, respectively, and compared with the
      protective effects of reduced glutathione and alpha-tocopherol. The comparison
      study was also performed using PC liposomes containing BSA. METHODS: BSA, PC
      liposomes or their mixtures were exposed to the HO.-generating system of AFE
      composed of 0.1 mM EDTA-Fe(3+) and 0.5 mM ascorbate in 0.1 M phosphate buffer, pH
      7.4, at 37 degrees C for 1 h. Oxidative damage of BSA was determined by measuring
      the carbonyl content and the fragmentation of protein by the reaction with
      dinitrophenylhydrazine (DNPH) and electrophoresis, respectively. Lipid
      peroxidation of PC liposomes was indicated by the quantity of malondialdehyde and
      4hydroxyalkenals. RESULTS: Melatonin inhibited protein damage as indicated by the
      reduced formation of carbonyl groups and fragmentation of BSA by AFE as
      effectively as did glutathione while alpha-tocopherol was ineffective. Melatonin
      also prevented lipid peroxidation to the same extent as did alpha-tocopherol in
      PC liposomes. CONCLUSION: Both BSA and PC lipid exposed to AFE are effectively
      protected by melatonin while hydrophilic glutathione and hydrophobic alpha
      tocopherol are as effective as melatonin only in one target, i.e., BSA or PC
      lipid, respectively.

PMID- 11455365
TI  - Daytime pineal gland activation in rats with colon tumors induced by 1,2
      dimethylhydrazine(3).
AB  - OBJECTIVES: Intact rats and rats with 1,2-dimethylhydrazine induced tumors of
      large intestine were used in experiments. Previously, blood melatonin
      concentration in these tumor-bearing rats was shown to increase at night, but not
      in the daytime. METHODS: The extracellular microelectrode registration of rat
      daytime pineal gland activity was performed. RESULTS: The existence of different
      types of pinealocytes in the pineal gland was confirmed. Tumor-bearing rats, in
      comparison to intact, demonstrated higher spike frequency due to cells switching
      from regular to pattern (4-6 times gain) activity and appearance of "fast" cells
      (>5Hz frequency). CONSLUSIONS: The literature about pinealocytes points to the
      correlation between electrical and secretory processes in pinealocytes; thus we
      suppose the groups of interacting cells, detected in tumor-bearing rats, to
      reflect cascade cells activation while pineal gland secretion increases. The
      results indicate, that in the daytime pinealocytes are secreting substances (not
      melatonin) in dependence with hormonal background.

PMID- 11455366
TI  - Tau-protein expression in human blood lymphocytes: a promising marker and
      suitable sample for life-time diagnosis of Alzheimer's disease.
AB  - OBJECTIVES: Taking into account the hypothesis that Alzheimer's disease (AD)
      might be a systemic disease that affects several tissues in the body, the aim of
      this study was to try to detect the expression of tau-protein in human peripheral
      blood lymphocytes (PBL) in patients with AD. MATERIAL AND METHODS: Blood samples
      were obtained from patients with AD (n=16, age 67-98) and from volunteers without
      psychoneurological pathology (n=10, age 65-78). PBL were isolated on Ficoll-Paque
      gradient centrifugation. For cell fixation and permeabilization we used a
      fixative solution (4% formaldehyde and 0.1% glutaraldehyde) and 0.03% Triton X
      100. Immunocytochemical detection of tau-protein was carried out by biotin
      streptavidin complex method with tau monoclonal antibody (1:100, clone TAU-2,
      ICN) and universal immunostaining kit IMMU-MARK (ICN). RESULTS: The expression of
      tau-protein was shown in PBL in absolute majority of AD patients studied. Only in
      two healthy volunteers a single lymphocyte from many cells (i.e. a smear)
      demonstrated a very weak-positive immunostaining to tau-protein CONCLUSION: This
      first demonstration of clear difference in localization of tau-protein in blood
      lymphocytes between healthy and sick people testifies to the fact that tau
      protein could be considered as a promising marker and blood lymphocytes as a
      suitable sample for life-time diagnosis of AD.

PMID- 11455367
TI  - Oncostatic activity of pineal neuroendocrine treatment with the pineal indoles
      melatonin and 5-methoxytryptamine in untreatable metastatic cancer patients
      progressing on melatonin alone.
AB  - OBJECTIVE: The recent advances in psycho-neuro-endocrino-immunology have
      demonstrated the existence of several endogenous neuroendocrine substances,
      capable of affecting both tumor growth and host anticancer immune defenses. The
      pineal gland would represent one of the most important organs releasing
      antiproliferative and immunostimulating substances, the most known of them is
      melatonin (MLT). However, MLT would not be the only pineal indole provided by
      antitumor activity. Other pineal indoles, namely 5-methoxytryptamine (5-MTT),
      would play antitumor effects, by either inhibiting cancer cell proliferation or
      stimulating the anticancer immunity. Preliminary data have shown that MLT may
      deserve antitumor activity in the treatment of human neoplasms, whereas at
      present there are no clear data about 5-MTT. In an attempt to obtain some
      preliminary data about the anticancer properties of 5-MTT in humans, we have
      evaluated the efficacy of MLT plus 5-MTT in untreatable advanced cancer patients
      progressing on MLT alone. METHODS: The study included 73 untreatable advanced
      solid tumor patients, who had progressed after two months of MLT therapy alone.
      According to tumor histotype, patients were randomized to receive MLT alone (20
      mg/day orally in the evening) or MLT plus 5-MTT (1 mg at noon orally), every day
      for at least two months. The clinical response was evaluated according to WHO
      criteria. RESULTS: A partial response (PR) occurred in two patients treated with
      MLT + 5-MTT and in none of the patients receiving MLT alone. A stable disease
      (SD) was achieved in only 2/37 patients on MLT therapy alone, and in 8/36
      patients receiving MLT plus 5-MTT. Therefore, the percent of non-progressing
      patients (SD + PR) obtained with MLT plus 5-MTT was significantly higher than
      that obtained with MLT alone. Moreover, the relief of asthenia and depressant
      symptoms was significantly higher in patients concomitantly treated with 5-MTT.
      DISCUSSION: This preliminary study would suggest that the concomitant
      administration of the less known pineal indole 5-MTT, also provided by
      antiproliferative and immunomodulating effects, may further amplify the
      oncostatic activity of the pineal hormone MLT in the palliative and curative
      therapy of advanced untreatable human solid neoplasms.

PMID- 11455368
TI  - Knowledge as an emotional and intellectual realization of the unconscious.
      Gnosiology, Psychedelic Drugs and Prenatal Experiences*
AB  - The use of psychedelic drugs in minute doses as an adjuvant psychotherapeutic
      means, within the context of Athanassios Kafkalides' autopsychognosia, caused the
      emotional revival of prenatal and perinatal experiences. This mnemonic process
      gives rise to a wide range of gnosiological questions such as, inter alia, those
      regarding the use of psychedelic drugs to stimulate memories and the difference
      between emotional and intellectual realization in the quest for knowledge. The
      new findings in this field necessitated profound changes of concepts like truth,
      reality, subjectivity, objectivity, unconscious, consciousness, cause and effect,
      emotions, intellect, quality, quantity, etc. The study presented here will deal
      with these issues in the context of gnosiotheoretical stands supported by
      thinkers from Plato to Feyerabend.

PMID- 11455369
TI  - Honoring the past, moving into the future.

PMID- 11455370
TI  - Preparing to practice and manage: A program for educating orthodontic residents
      in practice management.
AB  - The purpose of this article is to describe how the integration of practice
      management principles into orthodontic graduate programs can help young
      practitioners avoid many of the mistakes commonly made in developing an
      orthodontic practice and to provide guidelines and resources for starting off in
      the right direction. This article also describes how practice management
      education was integrated as one of the 4 principal components of contemporary
      orthodontic education at a California university. Specific goals, concepts, and
      components of a comprehensive practice management program are outlined. A
      structured practice management curriculum can provide opportunities for residents
      and alumni to learn some of the latest developments and techniques in orthodontic
      practice management.

PMID- 11455371
TI  - Is the postretention relapse of maxillary and mandibular incisor alignment
      related?
AB  - Previous studies suggest a poor association between initial and postretention
      pattern of incisor irregularity. One explanation may be that the incisor
      movements are limited by the boundaries provided by the incisors in the opposite
      arch. If so, postretention malalignment of the maxillary and mandibular incisors
      may be related. To test this hypothesis, long-term postretention study models of
      96 patients with acceptable occlusion at the time of appliance removal were
      examined. The occlusal surfaces of the postretention study models were
      photocopied, and tooth anatomical contact points were digitized. An algorithm was
      used to fit the dental arch to the digitized points. The amount of incisor
      rotation and anatomical contact point displacement of maxillary and mandibular
      anterior teeth, relative to their respective dental arches, were computer
      generated. Overbite, the number of occlusal contact points in the anterior
      segment, and concavity of the lingual surfaces of the maxillary incisors were
      recorded manually. Statistical analyses demonstrated a significant association (P
      <.05) between the overall irregularity of the maxillary and mandibular incisors.
      The association did not differ among subgroups that were stratified according to
      overbite or number of occlusal contacts. No associations were found for the
      overall amount of incisor rotation in the 2 arches (P >.05). The amount and
      direction of displacement of antagonistic pairs of maxillary and mandibular
      central incisors were also associated (P <.05), but not the amount and direction
      of rotation (P >.05). The lingual configuration of the maxillary incisors did not
      affect the pattern of mandibular incisor malalignment.

PMID- 11455372
TI  - Ask us. Does the use of a Herbst or a fixed functional appliance to treat a Class
      II malocclusion in the mixed dentition actually result in additional mandibular
      growth?

PMID- 11455373
TI  - The effect of preemptive and/or postoperative ibuprofen therapy for orthodontic
      pain.
AB  - The control of pain during orthodontic treatment is of vital interest to both
      clinicians and patients. Surprisingly, there has been limited research into the
      control of orthodontic pain, and there is no standard of care for controlling
      this discomfort. The purpose of this study was to compare the effectiveness of
      preemptive ibuprofen therapy, postoperative ibuprofen therapy, and a combination
      of the 2 therapies. Forty-one orthodontic patients aged 9 years 3 months to 16
      years 11 months who were to undergo separator placement were enrolled in this
      prospective study. Patients were randomly assigned to 1 of 3 experimental
      conditions: (1) 400 mg ibuprofen taken orally 1 hour before separator placement
      and 400 mg ibuprofen taken orally 6 hours after the initial dose, (2) 400 mg
      ibuprofen taken orally 1 hour before separator placement and a lactose capsule
      taken orally 6 hours after the initial dose, or (3) a lactose capsule taken
      orally 1 hour before separator placement and 400 mg ibuprofen taken 6 hours after
      the initial placebo. The results revealed that preemptive ibuprofen therapy
      significantly decreased pain that was experienced 2 hours after separator
      placement and at bedtime. Beginning on day 2, there was a trend for patients who
      had taken both preemptive and postoperative ibuprofen doses to have lower pain
      scores compared with the other 2 groups. In conclusion, these data indicate that
      ibuprofen taken 60 minutes before separator placement alleviates pain at 2 hours
      and at bedtime after treatment. Further study with the use of additional
      postoperative doses is warranted.

PMID- 11455374
TI  - Effects of combined application of antimicrobial and fluoride varnishes in
      orthodontic patients.
AB  - A randomized prospective clinical study, with 220 patients scheduled for fixed
      orthodontic therapy, was conducted to test the hypothesis that application of an
      antimicrobial varnish in combination with a fluoride varnish (group 1) is
      significantly more efficient in reducing white spot lesions on the labial
      surfaces than application of the fluoride varnish alone (group 2). The effects of
      the antimicrobial varnish on the occurrence of gingivitis and plaque formation
      were also studied. A third aim was to investigate whether white spot lesion
      development could be predicted early during treatment. The antimicrobial varnish
      significantly reduced the number of mutans streptococci in plaque during the
      first 48 weeks of treatment. This effect did not result in significantly less
      development of white spot lesions on the labial surfaces compared with the group
      receiving only the fluoride varnish application. There was however a clear trend
      that the combination of the antimicrobial and fluoride varnishes more effectively
      reduced the increments of new lesions on the maxillary incisors. It was
      speculated that this could be due partly to an inhibiting effect of the
      antimicrobial varnish in an area with low oral clearance (with low pH and loss of
      fluoride) and partly to an inhibiting effect of the varnish on mutans
      streptococci. No significant differences between the groups with respect to
      gingivitis and plaque were found. Lesion development was difficult to predict
      early after bonding, despite a number of caries-relevant parameters of
      orthodontic importance. The best predictors for white spot lesions at debonding
      were visible plaque and mutans streptococci (eg, the level of oral hygiene and
      thus the cariogenic challenge) around the appliance shortly after bonding.

PMID- 11455375
TI  - In vitro assessment of the mechanical properties of latex and non-latex
      orthodontic elastics.
AB  - The increased incidence of latex allergies has led to the development of non
      latex orthodontic products. The purpose of this study was to compare the
      mechanical properties of latex and non-latex orthodontic elastics. The elastics
      tested were from 2 manufacturers (GAC and Masel) and made of 2 materials (latex
      and non-latex). The properties tested included cross-sectional area, breaking
      force, peak load, peak stress, stiffness, modulus, hysteresis, and 24-hour load
      relaxation. The data were analyzed with 1-sample t tests, an analysis of
      variance, and the Fisher PLSD test. Between GAC and Masel, the GAC non-latex
      elastics had greater breaking forces than did the Masel non-latex elastics. The
      Masel latex elastics had greater breaking forces than did the Masel non-latex
      elastics. The GAC non-latex elastics showed more viscoelastic properties than
      both the GAC latex elastics and the Masel non-latex elastics; however, the Masel
      elastics were more viscoelastic than the GAC elastics. Forces generated by the
      elastics decreased over 24 hours to an average load approximating 75% of the
      manufacturers' values (GAC latex, Masel latex, and Masel non-latex elastics) and
      to 60% for the GAC non-latex elastics. The mechanical properties of the non-latex
      elastics were not comparable to those of the latex elastics. Therefore, the
      clinical choice of elastics should be based on the patient's medical history and
      the specific mechanical properties of the type of elastic.

PMID- 11455376
TI  - A review of orthodontic cements and adhesives.
AB  - Dental cements and resins are used intraorally to secure fixed orthodontic
      devices. Although cements are still used, the popularity of resin and resin
      cement hybrid materials is increasing because of their improved physical
      properties and low solubility in oral fluids. Some cements bond chemically to
      enamel, but bond strengths are low because cements are brittle and fracture
      cohesively. Resin adhesives penetrate micropores in etched enamel and mechanical
      retentions in orthodontic devices, resulting in higher bond strengths because
      resins are more fracture resistant than cements. Resins, however, do not bond
      well in the presence of moisture, and their attachment to surfaces is primarily
      mechanical. Hybridized materials combine the advantages of cements and resins but
      also have certain disadvantages. Optimal material selection and application
      require an understanding of the chemical differences and physical limitations of
      today's orthodontic cements, resins, and hybrid materials.

PMID- 11455377
TI  - Modified composite or conventional glass ionomer for band cementation? A
      comparative clinical trial.
AB  - The time to first failure, the position of band failure at deband, and the change
      in enamel white spot lesions of teeth bonded with a modified composite or a
      conventional glass ionomer were compared in a randomized half-mouth trial over
      the full course of orthodontic treatment. One hundred forty band pairs were
      cemented in 98 subjects. Overall band failure rates of 5% and 2.8% were recorded
      for the modified composite and the conventional glass ionomer, respectively, with
      no significant difference found between their times to first band failure. At the
      end-of-treatment deband, the position of band failure was predominantly at the
      enamel-cement interface for the modified composite and at the band-cement
      interface for the conventional glass ionomer (P <.001). A comparison of changes
      in mean enamel white spot lesion scores during treatment did not reveal
      significant differences between the cement groups (P =.16).

PMID- 11455378
TI  - The effect of moisture and blood contamination on bond strength of a new
      orthodontic bonding material.
AB  - The practice of orthodontics often requires the bonding of brackets under
      difficult conditions of moisture and/or blood contamination. Transbond MIP (3M
      Unitek, Monrovia, Calif) is a hydrophilic primer designed to bond in moist
      conditions. This study evaluated the bond strength of Transbond MIP under dry,
      moist, and blood-contaminated conditions. Ninety human premolars were bonded in 3
      equal groups with Transbond MIP after acid etching; the enamel surfaces were
      either dry, moist, or contaminated with human blood. The shear bond strength was
      recorded. Dry bonding resulted in a significantly higher bond strength (15.69
      MPa) than moist (12.89 MPa) or blood-contaminated (11.16 MPa) bonds. However, all
      bond strengths were in excess of previous reports of required clinical bond
      strength, and it was concluded that Transbond MIP is a suitable adhesive for
      bonding in conditions of poor moisture control or blood contamination.

PMID- 11455379
TI  - Orthodontic bracket bonding with a plasma-arc light and resin-reinforced glass
      ionomer cement.
AB  - Developments in light-curing technology have led to the introduction of a plasma
      arc light-curing unit that delivers high-intensity output for faster curing. The
      purposes of this study were to determine the shear bond strengths of light-cured
      resin-reinforced glass ionomer cement cured with a plasma-arc light-curing unit
      and to evaluate the durability of the resultant bond strength with thermal
      cycling. Comparisons were made between light-cured resin-reinforced glass ionomer
      cement and light-cured composite resin. Two light-curing units were used in this
      study: a plasma-arc light-curing unit and a conventional light-curing unit. The
      mean shear bond strengths of light-cured resin-reinforced glass ionomer cement
      with the plasma-arc and the conventional light-curing units were 20.3 MPa and
      26.0 MPa, respectively. An analysis of variance showed no statistically
      significant differences between the plasma-arc and the conventional light-curing
      units. Light-cured resin-reinforced glass ionomer cement and light-cured
      composite resin demonstrated similar bond strengths and exhibited no statistical
      differences. There was no statistical difference in bond strength between the
      teeth that were thermal cycled and those that were not. Failure sites for the
      brackets bonded with light-cured resin-reinforced glass ionomer cement appeared
      to be predominantly at the bracket-adhesive interface. The SDs of light-cured
      composite resin were high for both light-curing units. Whereas the coefficients
      of variation for light-cured resin-reinforced glass ionomer cement ranged from
      20% to 30%, those of light-cured composite resin ranged from 40% to 60%. The bond
      strength of light-cured resin-reinforced glass ionomer cement cured with either a
      conventional light-curing unit or a plasma-arc light-curing unit surpassed the
      clinically required threshold. The plasma-arc light-curing unit may be an
      advantageous alternative to the conventional light-curing unit for orthodontic
      bracket bonding with both light-cured resin-reinforced glass ionomer cement and
      light-cured composite resin.

PMID- 11455380
TI  - Variations in acid-etch patterns with different acids and etch times.
AB  - Research has shown that mandibular premolars have the highest rate of orthodontic
      bracket bond failure. Bond strength is thought to depend on the quality and
      quantity of enamel etch produced by the acid. Phosphoric acid is the most
      commonly used acid for etching before bonding. Nitric acid is also commercially
      available for etching enamel; however, it has not been studied specifically for
      etching in orthodontic bonding. This ex vivo study compared the enamel etch
      patterns achieved on the orthodontic bonding area of extracted mandibular
      premolars treated with 37% wt/wt phosphoric acid and 2.5% wt/wt nitric acid
      applied for 15, 30, or 60 seconds. The etch patterns were viewed with a scanning
      electron microscope and assessed with a 5-point etch scale. Statistical analysis
      showed that increasing the duration of acid application (irrespective of acid
      type) significantly increased the amount of better quality etch. Phosphoric acid
      at 37% concentration was more effective at producing a good-quality etch than was
      nitric acid at 2.5% for all 3 application times. The quantity of good-quality
      etch produced by phosphoric acid at 37% was time specific, with 15 seconds being
      significantly less effective than 30 or 60 seconds. However, 60 seconds was not
      significantly better than 30. Comparing the upper half of the orthodontic bonding
      area with the lower half showed no statistically significant differences for
      either acid type or length of application (P >.005). These findings support the
      use of 37% wt/wt phosphoric acid and indicate an optimum application time of 30
      seconds.

PMID- 11455381
TI  - Comparison of ion release from new and recycled orthodontic brackets.
AB  - Bracket corrosion can occur in the oral environment. The purpose of this study
      was to compare the release of metal ions from new and recycled brackets in
      artificial saliva and buffers with different pH values over a 12-week immersion
      period. The brackets were divided into 2 groups: new and recycled. The recycled
      bracket bases were coated with adhesive and the brackets were heat treated.
      Nickel, chromium, iron, and manganese ions were detected by atomic absorption.
      The surface characteristics of the brackets were examined by energy dispersive
      radiographic analysis. The results were as follows: (1) Recycled brackets
      released more ions than did the new brackets. (2) Greater amounts of nickel,
      iron, and manganese ions were released in artificial saliva than in the other
      buffers tested. (3) Ion release from brackets in a pH 4 buffer was greater than
      that observed in pH 7 or pH 10 buffers. (4) The total amount of ion release
      increased with time. (5) After a 12-week immersion, the total ion release
      averaged over the period did not exceed the recommended daily intake.

PMID- 11455382
TI  - Torsional properties of commercial nickel-titanium wires during activation and
      deactivation.
AB  - This study evaluated torsional moments on activation and deactivation in
      commercial, nickel-titanium wires that are intended for use in the initial phases
      of orthodontic treatment. Nine commercial, rectangular nickel-titanium wires
      (0.017 x 0.025 in) were tested in torsion. One wire was conventional nickel
      titanium, and the others were superelastic nickel-titanium wires. The specimens
      were tested in a torsiometer for rotations between 10 and 40 degrees in
      activation and deactivation. Wires E27, RF and R had the highest moments during
      activation and deactivation, without evidence of the plateau typical of the
      superelastic effect. Plateaus of constant moment were observed for wires C27,
      C35, E35, MO, NS, and NI. Torsional moments varied among superelastic nickel
      titanium wires, even with wires that had the same transition temperature range.
      Some superelastic wires had torsional moments that were comparable with
      conventional nickel-titanium wires.

PMID- 11455383
TI  - Computer-assisted orthodontic treatment: the SureSmile process.

PMID- 11455384
TI  - Litigation, legislation, and ethics. The duty of owners and occupiers of land.

PMID- 11455386
TI  - Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA
      association.
AB  - We determined the distribution of repressor-activator protein 1 (Rap1) and the
      accessory silencing proteins Sir2, Sir3 and Sir4 in vivo on the entire yeast
      genome, at a resolution of 2 kb. Rap1 is central to the cellular economy during
      rapid growth, targeting 294 loci, about 5% of yeast genes, and participating in
      the activation of 37% of all RNA polymerase II initiation events in exponentially
      growing cells. Although the DNA sequence recognized by Rap1 is found in both
      coding and intergenic sequences, the binding of Rap1 to the genome was highly
      specific to intergenic regions with the potential to act as promoters. This
      global phenomenon, which may be a general characteristic of sequence-specific
      transcriptional factors, indicates the existence of a genome-wide molecular
      mechanism for marking promoter regions.

PMID- 11455387
TI  - Aromatic hydrocarbon receptor-driven Bax gene expression is required for
      premature ovarian failure caused by biohazardous environmental chemicals.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are toxic chemicals released into the
      environment by fossil fuel combustion. Moreover, a primary route of human
      exposure to PAHs is tobacco smoke. Oocyte destruction and ovarian failure occur
      in PAH-treated mice, and cigarette smoking causes early menopause in women. In
      many cells, PAHs activate the aromatic hydrocarbon receptor (Ahr), a member of
      the Per-Arnt-Sim family of transcription factors. The Ahr is also activated by
      dioxin, one of the most intensively studied environmental contaminants. Here we
      show that an exposure of mice to PAHs induces the expression of Bax in oocytes,
      followed by apoptosis. Ovarian damage caused by PAHs is prevented by Ahr or Bax
      inactivation. Oocytes microinjected with a Bax promoter-reporter construct show
      Ahr-dependent transcriptional activation after PAH, but not dioxin, treatment,
      consistent with findings that dioxin is not cytotoxic to oocytes. This difference
      in the action of PAHs versus dioxin is conveyed by a single base pair flanking
      each Ahr response element in the Bax promoter. Oocytes in human ovarian biopsies
      grafted into immunodeficient mice also accumulate Bax and undergo apoptosis after
      PAH exposure in vivo. Thus, Ahr-driven Bax transcription is a novel and
      evolutionarily conserved cell-death signaling pathway responsible for
      environmental toxicant-induced ovarian failure.

PMID- 11455388
TI  - Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a
      genetic isolate of central Puerto Rico.
AB  - Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder
      characterized by oculocutaneous albinism and a storage pool deficiency due to an
      absence of platelet dense bodies. Lysosomal ceroid lipofuscinosis, pulmonary
      fibrosis and granulomatous colitis are occasional manifestations of the disease.
      HPS occurs with a frequency of one in 1800 in north-west Puerto Rico due to a
      founder effect. Several non-Puerto Rican patients also have mutations in HPS1,
      which produces a protein of unknown function. Another gene, ADTB3A, causes HPS in
      the pearl mouse and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a
      coat protein involved in vesicle formation, implicating HPS as a disorder of
      membrane trafficking. We sought to identify other HPS-causing genes. Using
      homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we
      localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24.
      The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal
      how new vesicles form in specialized cells. The homozygous, disease-causing
      mutation is a large deletion and represents the second example of a founder
      mutation causing HPS on the small island of Puerto Rico. We also present an
      allele-specific assay for diagnosing individuals heterozygous or homozygous for
      this mutation.

PMID- 11455389
TI  - Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1.
AB  - Brachydactyly type A-1 (BDA-1; MIM 112500) is characterized by shortening or
      missing of the middle phalanges (Fig. 1a). It was first identified by Farabee in
      1903 (ref. 2), is the first recorded example of a human anomaly with Mendelian
      autosomal-dominant inheritance and, as such, is cited in most genetic and
      biological textbooks. Here we show that mutations in IHH, which encodes Indian
      hedgehog, cause BDA-1. We have identified three heterozygous missense mutations
      in the region encoding the amino-terminal signaling domain in all affected
      members of three large, unrelated families. The three mutant amino acids, which
      are conserved across all vertebrates and invertebrates studied so far, are
      predicted to be adjacent on the surface of IHH.

PMID- 11455390
TI  - Next generation internet and pediatric cardiology.

PMID- 11455391
TI  - Body mass index can predict left ventricular diastolic filling in asymptomatic
      obese children.
AB  - To examine the effects of body mass index on left ventricular diastolic function,
      flow velocity patterns of the pulmonary vein and mitral valve were measured by
      pulse Doppler echocardiography in 21 asymptomatic obese children and were
      compared with those of an age-matched control population. The degree of obesity
      was calculated as (actual body mass index/ideal body mass index -1) x 100. The
      pulmonary venous flow indexes were peak systolic (S) and diastolic (D) velocities
      and peak D/S. The mitral inflow indexes were peak velocities of early diastole
      (E) and atrial contraction (A) and peak E/A. The pulmonary venous flow velocity
      pattern in obese patients was characterized by unchanged peak S, decreases in
      peak D (43 +/- 7 vs 51 +/- 8, p < 0.01) and peak D/S (0.98 +/- 0.19 vs 1.29 +/-
      0.20, p < 0.01), suggesting the reduction in the early diastolic filling. The
      peak D/S decreased significantly with an increase in the percentage body mass
      index (r = -0.84, p < 0.01). In contrast to the pulmonary venous flow pattern
      (peak D > peak S) as seen in normal controls, all of the obese patients with >
      70% over body mass index had abnormal pulmonary venous flow velocity patterns
      (peak D < peak S). The mitral flow velocity pattern in obese patients was also
      characterized by a decrease in early diastolic filling. However, these indices
      did not correlate with an increase in the percentage over body mass index. This
      study suggests that body mass index predicts the abnormality of left ventricular
      diastolic filling assessed by pulmonary venous flow patterns.

PMID- 11455392
TI  - Around pediheart: hyperlipidemia.

PMID- 11455393
TI  - Molecular characterization of tetralogy of fallot within Digeorge critical region
      of the chromosome 22.
AB  - The purpose of this study was to determine whether the levels of heterozygosity
      and microdeletion of specific loci within the DiGeorge critical region (del22q11)
      are associated with different phenotypes of tetralogy of Fallot (TF).
      Examinations were conducted on 84 sporadic TF patients and their unaffected
      parents for del22q11, using the following 9 simple tandem repeat polymorphic
      microsatellite markers: D22S420, D22S427, D22S941, D22S944, D22S264, D22S311,
      D22S425, D22S303, D22S257. The microdeletions were confirmed using quantitative
      PCR with markers TUPLE1, exon 2 of the UFD1L gene, and D22S264; the boundaries of
      these microdeletions were estimated using genotypic analyses of the unaffected
      family members. The del22q11 was identified in 14 patients (16.6%). The boundary
      of the shortest region of deletion overlap (SRO) in these 14 TF patients was
      identified, proximally using D22S427 and distally using the TUPLE 1 gene. The
      deletion of exon 2 of the UFD1L gene and TUPLE1 gene was identified in 13
      patients (13/14 cases; 93%). The SRO in TF patients with del22q11 was at or close
      to the ADU breakpoint and centromeric to the UFD1L gene. The level of
      heterozygosity for the marker D22S944 in TF patients without del22q11 (n = 70)
      was found to be significantly lower than expected. Overall, this study
      demonstrated the significantly low level of heterozygosity within DiGeorge
      critical region in TF patients with or without del22q11. Our results suggest that
      the genetic factors leading to DiGeorge/velocardiofacial syndrome might also be
      partly responsible for TF phenotypes.

PMID- 11455394
TI  - Patterns of right aortic arch and mirror-image branching of the brachiocephalic
      vessels without associated anomalies.
AB  - It is unusual to have a right aortic arch with mirror-image branching of the
      brachiocephalic vessels and no associated congenital cardiac anomalies.
      Pathogenetic factors of this anomaly, and associated development of the
      derivatives of the pharyngeal arches, have not been explored extensively. Eleven
      patients with a mirror-image right aortic arch and no intracardiac anomalies have
      undergone evaluation at our institution since 1987. Of these, 4 had stenosis (n =
      2) or atresia (n = 2) of the proximal left pulmonary artery. These included 2
      with bilateral ductus arteriosus. Six patients had a vascular ring formed by a
      ductus arteriosus or ligamentum arteriosum from the descending aorta to the left
      pulmonary artery. Six patients were evaluated for deletion within the DiGeorge
      critical region of chromosome 22q11. All 6 of the patients with a vascular ring
      underwent division of the ductus arteriosus or ligamentum through a left lateral
      thoracotomy. None of the patients with stenosis or atresia of the LPA have
      undergone intervention. Two of the 6 patients who underwent evaluation for
      chromosome 22q11 deletion were found to have the deletion. At a median follow-up
      of 7 years (15 months to 12 years), the patients who underwent division of the
      ring are all alive and asymptomatic. Two of these patients have undergone repeat
      magnetic resonance imaging, 1 of whom had mild residual tracheal compression. A
      right aortic arch with mirror-image branching of the brachiocephalic vessels and
      no associated intracardiac anomalies is extremely uncommon. We have observed two
      basic patterns of this lesion: (1) with associated abnormalities of the proximal
      left pulmonary artery, (2) with a vascular ring formed by a ductus arteriosus or
      ligamentum from the descending aorta to the left pulmonary artery. Pathogenetic
      considerations are explored, with a focus on flow-related vascular development
      and the role of deletions within chromosome 22q11.

PMID- 11455395
TI  - Hypoxia and cold stress on pulmonary venous obstruction.
AB  - Hemodynamic changes induced by hypoxia and cold stress were examined on the model
      of pulmonary venous obstruction (PVO) to investigate the mechanism of pulmonary
      hypertensive crisis. Bilateral pulmonary venous stenosis was surgically created
      in 7 newborn piglets of the PVO group. Sham operations were performed on 6
      piglets of the control group. Following the baseline hemodynamic measurement
      (FiO2 = 0.3) at 8 weeks after the operation, the piglets were exposed to hypoxia
      (FiO2 = 0.14) for 10 minutes, and were also exposed to cold stress for 20
      minutes. Hypoxia significantly increased mean pulmonary arterial pressure in the
      PVO group. Hypoxia increased not only pulmonary arterial resistance, but also
      pulmonary venous resistance in the PVO group. Cold stress did not change
      pulmonary arterial resistance or pulmonary venous resistance in each group. In
      the lungs of the PVO group, the medial muscular layer of the pulmonary arteries
      and pulmonary veins were thickened. This probably accelerates hypoxia-induced
      vasoconstriction, which in turn increases pulmonary arterial and venous
      resistances.

PMID- 11455396
TI  - Distinguishing cardiac features of a novel form of congenital muscular dystrophy
      (Salih cmd).
AB  - The cardiac features of a novel form of congenital muscular dystrophy (Salih CMD)
      are described in two adolescent siblings. The patients presented with severe
      hypotonia at birth, associated with delayed development. They could walk
      independently and managed to maintain walking after 13 years of age. Their muscle
      immunohistochemistry differed from that seen in Duchenne and Becher muscular
      dystrophy (DMD and BMD), severe childhood autosomal recessive muscular dystrophy
      (SCARMD) due to sarcoglycan deficiency (sarcoglycanopathies), and lamininalpha2
      (merosin)-deficient CMD. However, both patients had associated cardiomyopathy.
      Electrocardiography (ECG) in Salih CMD was characterized by delayed
      atrioventricular (AV) conduction, left anterior fascicular block (left axis
      deviation), and left atrial enlargement without evidence of atrial dysarrhythmia.
      Echocardiography showed features of severe left ventricular dysfunction with
      estimated left ventricle ejection fraction (LVEF) of 25% at 16 years-of-age in
      the older patient. A year later, multigated aquisition MUGA scan showed LVEF of
      21% and dilatation of the right ventricle. Echocardiography and MUGA scan were
      normal in the younger patient at 15 years-of-age. ECG, echocardiography, and MUGA
      scan are effective techniques for diagnosing and monitoring the cardiomyopathy in
      Salih CMD. They can also distinguish it from features seen in the other common
      forms of MD, including DMD, BMD, and sarcoglycanopathies.

PMID- 11455397
TI  - Spontaneous resolution of the septal defects in atrioventricular septal defect.
AB  - It is known that atrial septal defects of the secundum type and ventricular
      septal defects may undergo spontaneous closure. However, it is not well
      recognized that atrioventricular septal defects may infrequently also undergo
      spontaneous resolution. We report one case of complete atrioventricular septal
      defect that underwent spontaneous closure of the ventricular component. We also
      describe one case of partial atrioventricular septal defect with almost complete
      spontaneous resolution of the interatrial communication. Presence of shunting
      across the defects is demonstrated by color Doppler echocardiography, along with
      later absence of shunting. The rate of spontaneous resolution is estimated.

PMID- 11455398
TI  - Estimation of right ventricular free-wall mass using two-dimensional
      echocardiography.
AB  - Echocardiographic methods based on geometric models have long been in use for
      estimating left ventricular mass, but there is currently no similar method for
      estimating right ventricular (RV) free-wall mass. We hypothesized that a one
      quarter prolate ellipsoid model could be used with two-dimensional
      echocardiography to approximate RV mass. Over a 2-year period 39 patients who had
      both a complete cardiac magnetic resonance imaging (MRI) scan and an
      echocardiogram within 2 weeks of each other were retrospectively analyzed. MRI
      derived RV mass was used as the standard for comparison. Echocardiographic RV
      mass was estimated using three equations based on the geometric model. Linear
      regression analysis was performed to determine the correction factors used in the
      final formulae. The formula with the lowest standard error of the estimate was
      then prospectively analyzed for accuracy using a separate group of 88 subjects.
      The most accurate echocardiographic equation derived was RV mass = 5.84 (apical
      four-chamber RV cavity planar area) (RV free-wall thickness) + 1. Compared to MRI
      RV mass the correlation coefficient was 0.97 and the standard error of the
      estimate was 16.8%. The positive and negative predictive values for diagnosing RV
      hypertrophy were 95% and 88%, respectively. We conclude that RV free-wall mass
      can be estimated by two-dimensional echocardiography using a one-quarter prolate
      ellipsoid shell model.

PMID- 11455399
TI  - Recovery of high-frequency QRS potentials following cardioplegic arrest in
      pediatric cardiac surgery.
AB  - We examined the hypothesis that recovery of high-frequency QRS potentials at
      reperfusion is influenced by the duration of myocardial ischemia during
      cardioplegic arrest in pediatric cardiac surgery. Signal-averaged
      electrocardiograms were recorded after induction of anesthesia (baseline data)
      and every 1 to 5 minutes after aortic declamping in 14 patients aged 2 months to
      6 years. The signals were processed with a band-pass filter between 80 Hz and 300
      Hz to obtain high-frequency potentials in the QRS complex. The high-frequency QRS
      potentials (80-300 Hz) were expressed as the root mean square voltage over the
      filtered QRS complex. The high-frequency QRS potentials at baseline were 33.9 +/-
      4.4 microV. They decreased to 13.7 +/- 9.6 microV 1 minute after aortic
      declamping (p = 0.005). Subsequently they gradually increased and then returned
      to the baseline level. The time that the potentials were over 90% of baseline
      value ranged from 10 to 35 minutes after aortic declamping. The recovery time of
      this reduction in the high-frequency QRS potentials correlated with the duration
      of aortic cross-clamping (r = 0.80, p = 0.0009) and the value of postoperative MB
      isozyme of the creatine kinase (r = 0.81, p = 0.0042). This study demonstrated
      that the high-frequency QRS potentials decreased at early reperfusion following
      cardioplegic arrest and then returned to preischemic levels. The recovery time of
      the high-frequency QRS potentials significantly correlated with cardioplegic
      arrest time and postoperative MB isozyme of the creatine kinase values. Our
      results raise the possibility that changes in high-frequency electrocardiographic
      signals in the QRS complex may reflect myocardial ischemia during cardioplegic
      arrest.

PMID- 11455400
TI  - Around pediheart: right ventricular dysplasia.

PMID- 11455401
TI  - Acute renal insufficiency and renal replacement therapy after pediatric
      cardiopulmonary bypass surgery.
AB  - The aim of the study was to investigate renal function and renal replacement
      therapy after cardiopulmonary bypass surgery in children. Patient characteristics
      (sex, age, diagnosis), operation type, and death were listed. The study was
      performed retrospectively using serum creatinine level before, and peak values
      after, cardiopulmonary bypass surgery for assessment of renal function. Of the
      children on renal replacement therapy, indication, efficacy, and complications
      were recorded. In a 5-year period, 1075 children had cardiopulmonary bypass
      surgery at the Department of Cardiothoracic Surgery at Leiden University Medical
      Center and Academic Medical Center of Amsterdam. One-hundred eighty (17%)
      patients developed acute renal insufficiency. Twenty-five (2.3%) patients
      required renal replacement therapy. Peritoneal dialysis is a safe and effective
      treatment for children after cardiopulmonary bypass surgery. However, 15 (60%) of
      25 children on renal replacement therapy died of nonrenal causes. In 9 out of 10
      surviving children, renal function was normal at time of discharge from hospital.
      Acute renal insufficiency is a frequent complication after open-heart surgery,
      although renal replacement therapy was infrequently necessary. Peritoneal
      dialysis is a safe and effective therapeutic measure for children after cardiac
      bypass surgery.

PMID- 11455402
TI  - Prospective identification of anomalous origin of left coronary artery from the
      right sinus of valsalva using transthoracic echocardiography: importance of color
      Doppler flow mapping.
AB  - Four cases are discussed in which anomalous origin of the left coronary artery
      from the right sinus of Valsalva was identified prospectively by transthoracic
      echocardiography when the anomalous coronary passed between the great arteries.
      Color Doppler flow mapping was a critical component in identifying the anomalous
      coronary, particularly when the proximal course of the left main coronary was
      intramural.

PMID- 11455403
TI  - Around pediheart: absent pulmonary artery.

PMID- 11455404
TI  - Non-invasive imaging of the ring-sling complex in children.
AB  - The Ring-Sling Complex is an uncommon, congenital vascular and tracheobronchial
      malformation with a persistent high death rate. We report three patients in whom
      computed tomography (CT) and magnetic resonance imaging (MRI) were used for the
      preoperative diagnosis and for staging of the morphologic tracheal and vascular
      anomalies.

PMID- 11455405
TI  - Situs inversus totalis and corrected transposition of the great arteries [I,D,D]
      in association with a previously unreported vascular ring.
AB  - A 3-month-old girl with "noisy breathing" was found to have situs inversus
      totalis, corrected transposition of the great arteries [I,D,D], and a vascular
      ring. The ring was composed of a left aortic arch with normal branching pattern
      and a right ligamentum arteriosum that extended from a diverticulum off the
      descending aorta and coursed retroesophageal and to the right to join the
      pulmonary artery. There was no circumflex component of the aorta or aberrant
      subclavian artery. The descending aorta was left sided. Compression of the
      esophagus and trachea was noted on contrast esophagram, magnetic resonance
      imaging (MRI), and at the time of surgery to divide the vascular ring. In
      association with her corrected transposition, the patient also was shown to have
      a mild Ebstein's deformity of the right-sided (systemic) atrioventricular valve
      and electrocardiographic evidence of Wolfe-Parkinson-White syndrome. The
      combination of situs inversus totalis, corrected transposition of the great
      arteries [I,D,D], and an aortic arch anomaly has not been previously reported. In
      addition, the aortic arch anomaly suggested by MRI imaging and confirmed at
      surgery has previously only been postulated to exist but to our knowledge never
      reported.

PMID- 11455406
TI  - Pulmonary arteriovenous malformation in patients with total cavopulmonary shunt:
      what role does lack of hepatic venous blood flow to the lungs play?
AB  - We examined the etiology of a long-term postoperative complication, pulmonary
      arteriovenous malformation (PAVM), in a patient who underwent total cavopulmonary
      shunt (TCPS). The patient underwent TCPS at the age of 3 years and 1 month, and a
      PAVM developed. At the age of 10 years, TCPS was switched to total cavopulmonary
      connection to facilitate circulation of hepatic venous blood to the pulmonary
      artery. As a result, oxygen saturation increased. These findings suggest that the
      absence of pulmonary circulation of hepatic venous blood is involved in the
      development of PAVM.

PMID- 11455407
TI  - Origin of the main pulmonary artery from the left coronary artery in complex
      pulmonary atresia.
AB  - We describe a 22-year-old woman with a history of unrepaired pulmonary atresia
      with ventricular septal defect. This woman was interesting in that her main
      pulmonary artery and right pulmonary artery arose from the left main coronary
      artery. She developed significant pulmonary hypertension in addition to isolation
      of the left pulmonary artery following ductal closure, subsequent to which the
      majority of her pulmonary blood flow was coronary dependent.

PMID- 11455408
TI  - A sword for the left hand: an unusual case of left-sided scimitar syndrome.
AB  - Scimitar syndrome is a rare anomaly involving abnormalities of the heart and lung
      which classically involves the right side. A rare case of left-sided scimitar
      syndrome is described in an asymptomatic child, with a review of the literature.

PMID- 11455409
TI  - Congenital aneurysm of the muscular interventricular septum in a fraternal case
      diagnosed by fetal echocardiography.
AB  - Two siblings with aneurysms of the muscular ventricular septum are presented.
      Case 1 (the older brother) underwent fetal echocardiography at 26 weeks of
      gestation. Initially, it was thought that he had a muscular ventricular septal
      defect; however, postnatal echocardiography revealed an aneurysm of the muscular
      portion of the ventricular septum. Retrospective review of the 26-weeks gestation
      fetal echocardiogram confirmed this diagnosis. Case 2 (a younger brother of the
      first case) was also diagnosed as having an aneurysm of the ventricular septum by
      fetal echocardiography at 28 weeks of gestation. Postnatal echocardiography
      confirmed this diagnosis.

PMID- 11455410
TI  - Acute pulmonary embolism resulting from cardiac tumors associated with tuberous
      sclerosis.
AB  - A case report of a neonate with cardiac tumors in association with tuberous
      sclerosis is presented. The rare complication of pulmonary embolism and its
      successful treatment by anticoagulation and thrombolytic therapy is described.
      The treatment of these cardiac tumors is conservative, because the tumors regress
      spontaneously when the diagnosis is made in infancy. However, embolic event may
      rarely occur as a complication of cardiac tumors. If the cardiac tumors are
      treated conservatively, it is important to pay close attention to the occurrence
      of pulmonary embolism during the follow-up period.

PMID- 11455411
TI  - Aneurysm of the membranous septum in critical pulmonary stenosis: spontaneous
      rupture after balloon dilatation.
AB  - We report a case of critical pulmonary valve stenosis in which congenital
      aneurysm of the membranous septum ruptured spontaneously after balloon dilatation
      of the pulmonary valve. It is considered that the chronic mechanical trauma with
      phasic protrusion and collapse of the aneurysm during the cardiac cycles was
      responsible for an aneurysm rupture.

PMID- 11455412
TI  - Irreversible cardiac changes after dexamethasone treatment for bronchopulmonary
      dysplasia.

PMID- 11455415
TI  - The role of Ultrabithorax in the patterning of adult thoracic muscles in
      Drosophila melanogaster.
AB  - Mutations in the homeotic gene, Ultrabithorax (Ubx), result in the transformation
      of the third thoracic (T3) segment into the second thoracic (T2) segment.
      Although it has been well established that these mutations have striking effects
      on adult epidermal structures in T3, the effect of these mutations on the adult
      musculature has been controversial. In this study, a series of Ubx regulatory
      mutations, anterobithorax, bithorax, postbithorax, and bithoraxoid, as well as
      combinations of these alleles were used to reevaluate the role of Ubx in the
      patterning of the T3 musculature. Homeotic indirect and direct flight muscles
      (IFMs and DFMs) were identified in the transformed T3 segment of all alleles and
      allelic combinations with the exception of postbithorax. We critically evaluated
      the pattern and amount of these muscles and found that while the amount and/or
      quality of homeotic IFMs increased, the amount of homeotic DFMs did not vary
      significantly as the severity of the ectodermal transformation increased. Because
      Ubx is not expressed in the adult mesoderm of T3, these results suggest that
      inductive cues play a major role in the patterning of adult thoracic muscles. We
      provide a model that illustrates the central role of inductive cues in generating
      the final adult muscle pattern in the thorax.

PMID- 11455416
TI  - A search for Drosophila neural precursor genes identifies ran.
AB  - The Drosophila ran gene has been isolated in a differential cDNA screen designed
      to identify genes that are dynamically expressed in embryonic neuroblasts. The
      guanine triphosphate (GTP)-binding Ran protein, a member of the Ras superfamily,
      has been shown to participate in a variety of transport related processes in
      other organisms. Drosophila ran codes for a 216 amino acid (aa) protein that
      shares 78% and 86% identity with the yeast and human Ran proteins, respectively.
      Database searches have identified a second Drosophila ran gene, ran-like. The
      predicted Ran-like protein shares 59% identity with its isoform. Embryo in situ
      mRNA localization of ran and ran-like expression reveals that both are maternally
      expressed; however zygotic ran expression is restricted to central nervous system
      (CNS) neuroblasts undergoing late lineage formation, while ran-like expression is
      detected in the developing trachea and salivary gland. To investigate the
      significance of ran-restricted CNS expression, we have targeted its misexpression
      to different temporal windows of CNS development. In addition, a dominant
      negative mutant form of ran was targeted to the developing CNS and to the larval
      eye/antenna imaginal disc to assess the role of ran-dependent functions.
      Embryonic CNS misexpression of the mutant, but not wild-type, ran results in
      larval death. Neither wild-type nor mutant ran misexpression had any detectable
      effect on embryonic CNS lineage specification, nuclear transport of a number of
      CNS-specific transcription factors or axonal guidance. However, expression of the
      dominant-negative mutant ran in the developing eye/antenna disc did result in a
      severe adult eye phenotype marked by apoptosis of photoreceptor, cone and pigment
      cells.

PMID- 11455417
TI  - Double-stranded RNA interference in the spider Cupiennius salei: the role of
      Distal-less is evolutionarily conserved in arthropod appendage formation.
AB  - Chelicerates represent a basal arthropod group, which makes them an excellent
      system for the study of evolutionary processes in arthropods. To enable
      functional studies in chelicerates, we developed a double-stranded RNA
      interference (RNAi) protocol for spiders while studying the function of the
      Distal-less gene. We isolated the Distal-less gene from the spider Cupiennius
      salei. Cs-Dll gene expression is first seen in cells of the prosomal segments
      before the outgrowth of the appendages. After the appendages have formed, Cs-Dll
      is expressed in the distal portion of the prosomal appendages, and in addition,
      in the labrum, in two pairs of opisthosmal (abdominal) limb buds, in the head
      region, and at the posterior-most end of the spider embryo. In embryos, in which
      Dll was silenced by RNAi, the distal part of the prosomal appendages was missing
      and the labrum was completely absent. Thus, Dll also plays a crucial role in
      labrum formation. However, the complete lack of labrum in RNAi embryos may point
      to a different nature of the labrum from the segmental appendages. Our data show
      that the expression of Dll in the appendages is conserved among arthropods, and
      furthermore that the role of Dll is evolutionarily conserved in the formation of
      segmental appendages in arthropods.

PMID- 11455418
TI  - Micromere descendants at the blastula stage are involved in normal archenteron
      formation in sea urchin embryos.
AB  - Several lines of evidence suggest that micromere signaling plays a key role in
      endo-mesoderm differentiation along the animal-vegetal (A-V) axis in sea urchin
      embryos. A recent study has suggested that the activity of micromeres of inducing
      endoderm differentiation of mesomere descendants is, unexpectedly, maximal at the
      hatching blastula stage in the echinoids Scaphechinus mirabiris and Hemicentrotus
      pulcherrimus. In the present study, to confirm the inductive capacity of the
      micromere descendants in normal development, the timing of initiation of
      gastrulation and the elongation rate of the archenteron were examined in both
      micromereless embryos and in micromereless embryos cultured until the hatching
      blastula stage and then recombined with micromere descendants of the same age.
      The micromereless embryos consistently exhibited a delay in the initiation of
      gastrulation and a decrease in elongation rate of the archenteron, as compared
      with those in controls. In contrast, when the micromereless embryos cultured
      until the hatching blastula stage were recombined with micromere descendants of
      the same age, the recombinant embryos exhibited rescue of both the delay in
      initiation of gastrulation and a decrease in elongation rate of the archenteron.
      The delayed expression of alkaline phosphatase activity, an endoderm-specific
      marker, in the micromereless embryos was also rescued in the recombinant embryos.
      The recombined micromere descendants formed the larval spicules in the same
      schedule as that observed in the controls. These results indicate that at the
      hatching blastula stage, micromere descendants emanate a signal(s) required for
      normal gastrulation of the presumptive endo-mesodermal region.

PMID- 11455419
TI  - Pondering the procephalon: the segmental origin of the labrum.
AB  - With accumulating evidence for the appendicular nature of the labrum, the
      question of its actual segmental origin remains. Two existing insect head
      segmentation models, the linear and S-models, are reviewed, and a new model
      introduced. The L-/Bent-Y model proposes that the labrum is a fusion of the
      appendage endites of the intercalary segment and that the stomodeum is tightly
      integrated into this segment. This model appears to explain a wider variety of
      insect head segmentation phenomena. Embryological, histological, neurological and
      molecular evidence supporting the new model is reviewed.

PMID- 11455420
TI  - Homeotic evidence for the appendicular origin of the labrum in Tribolium
      castaneum.
AB  - The ontogeny of the insect labrum, or upper lip, has been debated for nearly a
      century. Recent molecular data suggest a segmental appendage origin of this
      structure. Here we report the first arthropod mutation associated with a homeotic
      transformation of the labrum. Antennagalea-5 (Ag(5)) transforms both antennal and
      labral structures to resemble those of gnathal appendages in Tribolium castaneum.
      This labral transformation suggests that the labrum is a fused structure composed
      of two pairs of appendage endites, and is serially homologous to the gnathal
      appendages.

PMID- 11455421
TI  - The Mnx homeobox gene class defined by HB9, MNR2 and amphioxus AmphiMnx.
AB  - The HB9 homeobox gene has been cloned from several vertebrates and is implicated
      in motor neuron differentiation. In the chick, a related gene, MNR2, acts
      upstream of HB9 in this process. Here we report an amphioxus homologue of these
      genes and show that it diverged before the gene duplication yielding HB9 and
      MNR2. AmphiMnx RNA is detected in two irregular punctate stripes along the
      developing neural tube, comparable to the distribution of 'dorsal compartment'
      motor neurons, and also in dorsal endoderm and posterior mesoderm. We propose a
      new homeobox class, Mnx, to include AmphiMnx, HB9, MNR2 and their Drosophila and
      echinoderm orthologues; we suggest that vertebrate HB9 is renamed Mnx1 and MNR2
      be renamed Mnx2.

PMID- 11455422
TI  - Drosophila SAP18, a member of the Sin3/Rpd3 histone deacetylase complex,
      interacts with Bicoid and inhibits its activity.
AB  - Bicoid directs anterior development in Drosophila embryos by activating different
      genes along the anterior-posterior axis. However, its activity is down-regulated
      at the anterior tip of the embryo, in a process known as retraction. Retraction
      is under the control of the terminal polarity system, and results in localized
      repression of Bicoid target genes. Here, we describe a Drosophila homolog of
      human SAP18, a member of the Sin3A/Rpd3 histone deacetylase complex. dSAP18
      interacts with Bicoid in yeast and in vitro, and is expressed early in
      development coincident with Bicoid. In tissue culture cells, dSAP18 inhibits the
      ability of Bicoid to activate reporter genes. These results suggest a model in
      which dSAP18 interacts with Bicoid to silence expression of Bicoid target genes
      in the anterior tip of the embryo.

PMID- 11455423
TI  - Ecdysteroid-induced programmed cell death and cell proliferation during pupal
      wing development of the silkworm, Bombyx mori.
AB  - The wing margin of adult wings of Lepidoptera is defined by the position of a
      "bordering lacuna"(BL). During adult wing development, cell proliferation and
      scale formation proximal to this lacuna and programmed cell death distal to the
      lacuna are generally observed. To determine the effect of 20-hydroxyecdysone
      (20E) on these events, we cultured the silkworm pupal wings with or without 20E
      and analyzed regional specificity for cell death by the TUNEL method and cell
      proliferation by 5-bromodeoxyuridine labeling. Programmed cell death was induced
      by 20E after 5 days of culture and was detected only in the region distal to BL.
      Cell proliferation after 1 day of culture and scale formation after 5 days of
      culture were also inducible by 20E and detected in the region proximal to BL.
      These results suggest that two types of pupal wing cells, which are divided by
      the position of the BL, respond to ecdysteroid in different manners. Higher
      concentrations of 20E (more than 1,000 ng/ml) repressed the scale formation,
      while such repression could not be observed in the peripheral cell death even
      with 5,000 ng/ml 20E. The ecdysteroid may work both as a trigger to make the wing
      margin and scales and as a developmental timer to arrange these cellular
      responses.

PMID- 11455424
TI  - Development of the sensory system in larvae and pupae of Chaoborus crystallinus
      (DeGeer, 1776; Diptera, Chaoboridae): sensory cells, nerves and ganglia of the
      tail region.
AB  - Using various microscopical techniques, we have studied changes in the sensory
      equipment and architecture of the peripheral nervous system (PNS) around the
      first metamorphic molt from larva to pupa in the phantom midge Chaoborus. The
      transparent larvae and pupae of this dipteran with ancestral features allow us to
      investigate sensilla and their central projections from whole-mount preparations
      of complete groups of segments. Each sensillum on the posterior larval and pupal
      segments was identified using its external shape and position, and the morphology
      of the abdominal ganglia and segmental nerves was investigated. In addition,
      retrograde fills with the carbocyanine dye DiI were used to trace the axonal
      paths of most of the extero- and proprioreceptors. These findings were combined
      to produce maps of the sensory elements of larval and pupal abdomens that were
      analyzed at three levels: seriality (homonomy), ontogenetic changes of individual
      sensilla, and homology of the PNS between different species. Comparison of
      different segments shows for both stages that primarily there is a homonomous
      basic design of the PNS, but segment-specific modifications are evident in
      segments 8-10. Comparison of corresponding larval and pupal segments shows that
      many sensilla retain their internal structure and axonal projections. However,
      their external cuticular parts are changed in relation to the different life
      habits of larvae and pupae. Furthermore, some sensilla are completely reduced
      during the pupal molt, especially those of the tenth segment which appears as a
      distinct larval structure (caenogenesis). Comparison between species indicates
      that despite the varying types of sensilla their basic segmental arrangement and
      their axonal trajectories are conserved.

PMID- 11455425
TI  - Early and late changes in Pax6 expression accompany eye degeneration during
      cavefish development.
AB  - We have compared Pax6 expression during embryonic development in the eyed surface
      form (surface fish) and several different eyeless cave forms (cavefish) of the
      teleost Astyanax mexicanus. Despite lacking functional eyes as adults, cavefish
      embryos form small optic primordia, which later arrest in development and show
      various degrees of eye degeneration. The pattern of Pax6 mRNA expression was
      modified early and late during cavefish development. In early surface fish
      embryos, two bilateral Pax6 expression domains are present in the anterior neural
      plate, which extend across the midline and fuse to form the forebrain and optic
      primordia. In cavefish embryos, these Pax6 domains are diminished in size and
      remain separated, resulting in an anterior gap in Pax6 expression and presumably
      the formation of smaller optic primordia. The anterior gap in Pax6 expression was
      confirmed by double staining for Pax6 and distalless-3 mRNA, which marks the
      anterior margin of the neural plate and is unaltered in cavefish. Similar
      anterior gaps in Pax6 expression occurred in independently derived cavefish
      populations, suggesting that they are important in eye degeneration. Later during
      surface fish development, Pax6 protein is expressed in the cornea, lens, and
      ganglion and amacrine cells of the neural retina. Pax6 expression was gradually
      reduced during cavefish lens development, concomitant with lens arrest and
      degeneration, and was absent in the corneal epithelium, which does not
      differentiate in cavefish. In contrast, Pax6 expression in the retinal ganglion
      and amarcine cells is unmodified in cavefish, despite retarded retinal
      development. The results suggest that changes in Pax6 expression are involved in
      the evolution of cavefish eye degeneration.

PMID- 11455426
TI  - A cis-regulatory element essential for photoreceptor cell-specific expression of
      a medaka retinal guanylyl cyclase gene.
AB  - We examined the spatial expression pattern of an orphan receptor guanylyl cyclase
      gene, OlGC3, during embryogenesis of medaka, and we analyzed the cis-regulatory
      region required for its photoreceptor cell-specific expression by introducing
      promoter-green fluorescent protein gene (GFP) fusion constructs into medaka
      embryos. Zygotic expression of OlGC3 first appears at stage 36 and is confined to
      retinal photoreceptor cells. The 5' flanking sequence up to -388 is sufficient to
      drive the photoreceptor cell-specific gene expression. When a mutation was
      introduced into the orthodenticle-related homeobox (OTX)-binding consensus
      sequence at -36/-31, reporter gene expression was completely abolished in retinal
      photoreceptor cells. The mutation seemed not to impair promoter elements for
      general transcription factors, because ectopic GFP expression in yolk epithelium
      was not diminished by the same mutation. These results suggest that the proximal
      cis-regulatory element containing a consensus binding sequence for OTX
      transcription factors is essential for OlGC3 expression in photoreceptor cells.

PMID- 11455427
TI  - Tyrosinase gene expression in zebrafish embryos.
AB  - The enzyme tyrosinase is required for the conversion of tyrosine into the pigment
      melanin. Thus, tyrosinase gene expression is a useful marker for studying the
      differentiation of melanin-expressing cells during embryogenesis. We describe the
      spatiotemporal pattern of transcription of the tyrosinase gene and the presence
      of active enzyme in whole embryos of the zebrafish, Danio rerio. At 16.5 h post
      fertilisation the tyrosinase gene is transcribed in the dorsal extremity of the
      developing retinal pigment epithelium, approximately 7 h before visible
      pigmentation. Shortly thereafter, transcription in neural crest-derived
      melanocytes is first observed dorsolateral to the mesencephalon and diencephalon
      and the posterior hindbrain/anterior spinal cord. A wave of gene activation and
      cell migration is then observed moving towards the posterior of the animal. DOPA
      staining for tyrosinase activity shows the presence of active enzyme in embryos
      at least 3 h before visible pigmentation.

PMID- 11455428
TI  - Endogenous beta-galactosidase activity in amphioxus: a useful histochemical
      marker for the digestive system.
AB  - Endogenous beta-galactosidase activity has been shown in the digestive tract of
      amphioxus from the larval to the adult stage and it can be easily followed as a
      histochemical marker. Enzymatic activity first appeared in 30-h larvae, became
      evident in 36-h larvae and remained in adults. In situ detection of beta
      galactosidase activity was used to monitor morphological and functional
      differentiation of the digestive system and the posteriorization of the
      endodermal structures in retinoic-acid treated embryos. The endogenous beta
      galactosidase activity was distinguished from the bacterial lacZ reporter by
      incubation at low pH.

PMID- 11455429
TI  - Brachyury is expressed in gastrulating bovine embryos well ahead of implantation.
AB  - Brachyury is a T-box-containing transcription factor involved in mesoderm
      formation during vertebrate gastrulation. To analyse whether the regulation of
      gastrulation varies as much as the timing of gastrulation does with respect to
      implantation, we isolated a bovine brachyury cDNA fragment. The amino acid
      sequence shows high similarity to mouse and human Brachyury and clear differences
      to other T-box genes. Whole-mount in situ hybridisation reveals a normal
      expression pattern except for a transiently reduced expression in the anterior
      part of the primitive streak. According to these results, gastrulation in mammals
      is implemented and regulated irrespective of implantation.

PMID- 11455430
TI  - Expression of the Ror1 and Ror2 receptor tyrosine kinase genes during mouse
      development.
AB  - Ror1 and Ror2 are orphan receptor tyrosine kinases that are most closely related
      to MuSK and the Trk family of neurotrophin receptors. We report the results of an
      extensive in situ hybridisation survey of the expression of these genes during
      mouse development. Expression of Ror1 and Ror2 differs markedly at early stages
      (E8.5--E9.5). At these times, Ror2 is expressed much more widely than Ror1,
      expression of which is largely restricted to head mesenchyme. At later stages of
      development (E12.5--E14.5), Ror1 expression expands and Ror2 expression becomes
      more restricted than at earlier times, although expression of Ror1 continues to
      be more restricted than that of Ror2. These changes result in overlapping
      expression domains but with major differences remaining. In many cases Ror1 is
      expressed in a sub-set of Ror2-expressing tissues; in others, there is
      complementary expression of Ror1 and Ror2. Ror1 and Ror2 are both expressed in
      derivatives of all three germ layers and in most organ systems, including the
      nervous, circulatory, respiratory, digestive, urogenital and skeletal systems.
      Conspicuous themes are the expression in major sense organs, and in neural crest
      and its derivatives.

PMID- 11455431
TI  - The caudal gene of the barnacle Sacculina carcini is not expressed in its
      vestigial abdomen.
AB  - We report the characterization of a caudal gene from the rhizocephalan cirripede
      Sacculina carcini and its embryonic and larval expression patterns. Cirripedes
      are maxillopodan crustaceans that are devoid of any complete abdominal segment at
      the adult stage. We currently explore the genetic basis of this peculiar body
      plan. In a previous study we have shown that they probably lack the abdominalA
      gene, while possessing the other Hox genes shared by arthropods. However, at
      least a part of the genetic program might be conserved, since the engrailed.a and
      engrailed.b genes are expressed in a posterior region that we interpret as a
      relic of an ancestral abdomen. Here we show first that the Sacculina caudal gene
      is expressed early in embryogenesis, which makes it the earliest genetic marker
      evidenced in the development of Sacculina and of any other crustacean species. It
      is expressed later in the embryo in the caudal papilla, a posterior proliferating
      zone of cells. During the larval stages, the caudal gene is first expressed in
      the whole thoracic region; then its expression regresses to the posterior end of
      the larva. Surprisingly, it is never expressed in the vestigial abdomen. This
      lack of expression of the Sacculina caudal gene in a posterior region, at odds
      with what is known in all other studied metazoan species, might be correlated
      with the defective development of the abdomen.

PMID- 11455432
TI  - Imprint status of M6P/IGF2R and IGF2 in chickens.
AB  - Genomic imprinting is a method of gene regulation whereby a gene is expressed in
      a parent-of-origin-dependent fashion; however, it is hypothesized that imprinting
      should not occur in oviparous taxa such as birds. Therefore, we examined the
      allelic expression of two genes in the chicken that are reciprocally imprinted in
      most mammals, mannose 6-phosphate/insulin-like growth factor 2 receptor
      (M6P/IGF2R) and insulin-like growth factor 2 (IGF2). Single nucleotide
      polymorphisms were identified in these genes, and cDNA was prepared from several
      tissues of embryos heterozygous for these polymorphisms. Both alleles of
      M6P/IGF2R and IGF2 were expressed in all tissues examined by RT-PCR. Since the
      expression of these genes was independent of the parent from which they were
      inherited, we conclude that neither M6P/IGF2R nor IGF2 are imprinted in the
      chicken.

PMID- 11455433
TI  - Isolation and characterization of genes that are expressed during Ciona
      intestinalis metamorphosis.
AB  - In ascidians, the events of metamorphosis transform the non-feeding, mobile
      tadpole larva into a filter-feeding, fixed juvenile, and the process involves
      rearrangements of cells, two organs and physiological changes. Differential
      screening was used to isolate two genes that are not expressed in swimming larvae
      but are expressed immediately after the initiation of metamorphosis in Ciona
      intestinalis. One of the genes, Ci-meta1, encodes a polypeptide with a putative
      secretion signal sequence, 6 epidermal growth factor (EGF)-like repeats and 13
      calcium-binding EGF-like repeats. The gene begins to be expressed immediately
      after the beginning of metamorphosis in the adhesive organ and is likely to be
      associated with the signal response for metamorphosis. Another gene named Ci
      meta2 encodes a protein with a putative secretion signal and three thrombospondin
      type-1 repeats. Ci-meta2 gene expression begins at the larval stage and is
      upregulated in the metamorphosing juveniles. Ci-meta2 expression is found in
      three regions; the adhesive organ which is also associated with settlement, the
      neck region between the trunk and the tail of the larva which is associated with
      tail resorption, and dorsal regions of the trunk which correspond to the location
      of the siphon primordium. This gene may be involved in the dynamic arrangement of
      cells during ascidian metamorphosis.

PMID- 11455434
TI  - Isolation of genes involved in ascidian metamorphosis: epidermal growth factor
      signaling and metamorphic competence.
AB  - Although embryonic development in ascidians has been studied for over a century,
      the signals involved in coordinating post-larval development and metamorphosis
      are just beginning to be investigated. In this paper, we demonstrate that
      transcription is necessary for both the acquisition of metamorphic competence and
      the completion of the initial events of metamorphosis in Boltenia villosa.
      Transcripts expressed during metamorphic competence were isolated by a
      suppressive PCR subtraction of Boltenia villosa larval cDNAs. One of these
      transcripts is homologous to cornichon. Cornichon has a crucial but undefined
      role in epidermal growth factor (EGF) signaling during Drosophila embryogenesis.
      In situ hybridization demonstrates that Boltenia cornichon (Cnib) is expressed in
      the anterior papillary region of larvae as they gain competence. Our hypothesis
      is that Cnib acts to potentiate EGF signaling, thereby allowing Boltenia larvae
      to respond to cues for metamorphosis. Further research into the role of Cnib in
      urochordate metamorphosis may provide insight into the function of cornichon in
      other organisms. A better molecular understanding of urochordate metamorphosis
      will also provide a foundation for exploring the role of metamorphosis in
      chordate evolution.

PMID- 11455435
TI  - Expression of the Xenopus homologue of the receptor for activated C-kinase 1
      (RACK1) in the Xenopus embryo.
AB  - We have isolated the Xenopus homologue of the receptor for activated C-kinase 1
      (RACK1), whose amino acid sequence shows significant similarity with other
      vertebrate RACK1s. XRACK1 is a maternally expressed gene and its zygotic
      expression is detected in the antero-dorsal region and dorsal midline in the late
      neurula. At tailbud stage, rather diffuse staining is seen in the somite and
      head. Later, XRACK1 mRNA is expressed highly in ventrally migrating abdominal
      muscle anlagen, where it remains expressed during subsequent stages.

PMID- 11455436
TI  - Epaxial-adaxial-hypaxial regionalisation of the vertebrate somite: evidence for a
      somitic organiser and a mirror-image duplication.
AB  - During vertebrate neural tube formation, the initially lateral borders between
      the neural and epidermal ectoderm fuse to form the definitive dorsal region of
      the embryo, while the initially dorsally located notochord-floor plate complex is
      being internalised. Along the definitive dorso-ventral body axis, one can
      distinguish an epaxial (dorsal to the notochord) and a hypaxial (ventral to the
      notochord) body region. The mesodermal somites on both sides of the notochord and
      neural tube give rise to the trunk skeleton and skeletal muscle. Muscle forms
      from the somite-derived dermomyotomes and myotomes that elongate dorsally and
      ventrally. Based on gene expression patterns and comparative embryology, it is
      proposed here that the epaxial (dermo)myotome region in amniote embryos is
      subdivided into a dorsalmost and a centrally intercalated subregion. The
      intercalated subregion abuts to the hypaxial (dermo)myotome region that elongates
      ventrally via the hypaxial somitic bud. The dorsalmost subregion elongates
      towards the dorsal neural tube and is proposed to derive from an epaxial somitic
      bud. The dorsalmost and hypaxial somite derivatives share specific gene
      expression patterns which are distinct from those of the intercalated somite
      derivatives. The intercalated somite derivatives develop adaxially, i.e. at the
      level of the notochord-floor plate complex. Thus, the dorsalmost and intercalated
      (dermo)myotome subregions may be influenced preferentially by signals from the
      dorsal neural tube and from the notochord-floor plate complex, respectively.
      These (dermo)myotome subregions are sharply delimited from each other by
      molecular boundary markers, including Engrailed and Wnts. It thus appears that
      the molecular network that polarises borders in Drosophila and vertebrate
      embryogenesis is redeployed during subregionalisation of the (dermo)myotome. It
      is proposed here that cells within the amniote (dermo)myotome establish polarised
      borders with organising capacity, and that the epaxial somitic bud represents a
      mirror-image duplication of the hypaxial somitic bud along such a border. The
      resulting epaxial-intercalated/adaxial-hypaxial regionalisation of somite
      derivatives is conserved in vertebrates although the differentiation of
      sclerotome and myotome starts heterochronically in embryos of different
      vertebrate groups.

PMID- 11455437
TI  - Brachyury (T) gene expression and notochord development in Oikopleura longicauda
      (Appendicularia, Urochordata).
AB  - Appendicularia (Larvacea) is a subgroup of Urochordata (Tunicata) comprised of
      holoplanktonic organisms that retain their tailed architecture throughout their
      life history, while other tunicates, including ascidians and doliolids, resorb
      the tail after metamorphosis. In order to investigate the characteristics of the
      appendicularian unresorbed notochord, we isolated a partial genomic clone and a
      full-length cDNA sequence homologous to the mouse Brachyury (T) gene from the
      appendicularian Oikopleura longicauda. Brachyury is known to be predominantly
      expressed in the notochord cells and plays an important role in their
      differentiation in other chordates. While phylogenetic analysis robustly supports
      the orthology of the isolated Brachyury gene, the exon-intron organization found
      in the genomic clone was distinct from that well-conserved among other T-box
      genes. In addition to a detailed observation of notochord development in living
      specimens, whole-mount double in situ hybridization was carried out using a
      Brachyury probe along with a muscle actin probe. The Brachyury transcripts were
      found in the notochord of the tailbud embryos and persisted into later stages.
      The present study highlights characteristics of notochord development in the
      appendicularian. Furthermore, these results provide basic knowledge for
      comprehensive understanding of the cellular- and molecular-based mechanisms
      needed to build the characteristic cytoarchitecture of notochord that varies
      among tunicate species.

PMID- 11455438
TI  - Distal-less expression in embryos of Limulus polyphemus (Chelicerata, Xiphosura)
      and Lepisma saccharina (Insecta, Zygentoma) suggests a role in the development of
      mechanoreceptors, chemoreceptors, and the CNS.
AB  - The homeobox gene Distal-less (Dll) is well known for its participation in the
      development of arthropod limbs and their derivatives. Dll activity has been
      described for all groups of arthropods, but also for molluscs, echinoderms and
      vertebrates. Generally, Dll participates in the establishment of the proximo
      distal-axis and differentiation along this axis. During our investigation of the
      expression pattern in the silverfish Lepisma saccharina and the horseshoe crab
      Limulus polyphemus, we found several expressions in late stages which cannot be
      explained with the "normal" limb-specific function. The antenna, cerci and
      terminal filament of the silverfish show a striped expression; single cells on
      the labrum, mandibles, maxillary palps and anal valves are also strongly stained
      by the Dll antibody. In addition to cell groups in the developing ganglia of the
      CNS, in the coxal endites and several nerve cells in femur and the trochanter of
      the prosomal limbs, the whole prosomal shield of Limulus polyphemus is surrounded
      by Dll-positive cell clusters. Furthermore, the lateral processes of the
      opisthosoma and the edges of the opisthosomal appendages are Dll positive. To get
      an indication of the cell fate of these regions, we examined hatched larvae and
      juvenile stages of both species with the SEM. We found a striking correlation of
      these Dll-positive areas and different sense organs, especially mechanoreceptors.
      Since many sense organs in arthropods are situated on the limbs, interpretation
      of the Dll expression in limbs is problematical. This has critical implications
      for comparative analysis of Dll expression patterns between arthropods and for
      the claim of homology between limb-like structures. Furthermore, we discuss the
      possibility of convergent appendage evolution in various bilaterian groups based
      on the improvement of spatial sensory resolution.

PMID- 11455439
TI  - Molecular characterization of Tclabial and the 3' end of the Tribolium homeotic
      complex.
AB  - The homeotic selector gene labial is located at the 3' end of the Antennapedia
      complex (ANTC) and is required for proper head development in Drosophila. We have
      cloned and characterized the Tribolium ortholog of labial, Tclabial (Tclab).
      Similar to Drosophila labial, Tclab contains a single large intron upstream of
      the homeobox. In contrast, Tclab lacks an intron within the homeobox. The
      Tribolium ortholog of chaoptic, Tcchaoptic, transcribed from the opposite strand,
      is located immediately downstream of the homeotic complex, and its 3'UTR overlaps
      that of Tclab by 50 nucleotides. We have also sequenced the 13.5 kb interval
      between Tclab and maxillopedia (the Tribolium ortholog of Drosophila
      proboscipedia). In contrast to Drosophila, there is not a cluster of cuticle
      genes in this region. Finally, we have examined the expression of Tclab
      transcripts in Tribolium embryos. As previously described for Drosophila and
      other insects, the expression of Tclab is specific to the intercalary segment.

PMID- 11455440
TI  - Changes in gelsolin expression during ascidian metamorphosis.
AB  - Gelsolin is an actin regulatory protein that is expressed in a wide variety of
      tissues and is especially abundant in muscle and blood cells. The role of
      gelsolin during structural reorganization of the body, such as during
      metamorphosis or regeneration, is poorly understood. We analyzed changes in
      gelsolin expression during ascidian embryogenesis and metamorphosis using nucleic
      acid probes and a monoclonal antibody (AS23) specific for ascidian gelsolin; our
      results indicated that gelsolin is maternally provided and that its de novo gene
      transcription is initiated during the neurula stage. In the larva, gelsolin was
      detectable in specific types of nerve cells, i.e. the adhesive papillae, motor
      neurons and epidermal sensory neurons. During metamorphosis, the expression of
      gelsolin changes markedly: the expression is suppressed in nerve tissues after
      tail resorption but is induced in mesodermal tissues. Gelsolin accumulated in
      mesenchyme cells until the onset of tail resorption, and following tail
      resorption, these cells migrated to the tunic and differentiated into tunic cells
      with many fine processes. Migration of the mesenchyme cells into the tunic was
      completely inhibited by treatment with cytochalasin B. Gelsolin was colocalized
      with actin in tunic cells, suggesting that it is involved in the rearrangement of
      actin filaments during cell locomotion or morphogenesis.

PMID- 11455441
TI  - Developmental expression of the Xenopus Iroquois-family homeobox genes, Irx4 and
      Irx5.
AB  - We have isolated and characterized the developmental expression of the Xenopus
      Iroquois 4 (Irx4) and Iroquois 5 (Irx5) homeodomain transcription factors. Irx4
      is expressed in a subset of cells in the neural retina and the developing
      hindbrain and also, specifically, in the ventricle of the heart. Xenopus Irx5 is
      expressed in the developing midbrain, hindbrain, neural tube, and also in the
      retina.

PMID- 11455442
TI  - TTP, a C3H zinc finger protein gene, is expressed in mouse ovarian oocytes.
AB  - The gene TTP, encoding a C3H zinc finger protein of the TIS11 family, is
      expressed in growing mouse oocytes. The gene is downregulated in Graafian
      follicles shortly before ovulation. This corresponds to a possible function in
      regulation of maternal mRNA translation, a function attributed to related C3H
      class genes in Caenorhabditis elegans, zebrafish, and Xenopus.

PMID- 11455443
TI  - DrhoGEF3 encodes a new Drosophila DH domain protein that exhibits a highly
      dynamic embryonic expression pattern.
AB  - The Rho GTPases regulate many different cellular and developmental processes, and
      activation of Rho GTPase signalling is mediated through interaction with the Dbl
      homology (DH) protein domain. We describe the expression pattern of DrhoGEF3
      (cytological position 61B1-B3), which encodes a new member of the DH domain
      protein family from Drosophila and is a homologue of the human protein hPEM-2.
      During gastrulation and germ band extension, DrhoGEF3 exhibits a segmented
      expression pattern. DrhoGEF3 is subsequently expressed in the visceral mesoderm,
      at the sites of muscle attachment and in specific groups of sub-epidermal cells.
      The possible function of such a dynamically expressed signalling molecule is
      discussed.

PMID- 11455444
TI  - Striatal input from the ventrobasal complex of the rat thalamus.
AB  - We have analyzed whether caudal regions of the caudate putamen receive direct
      projections from thalamic sensory relay nuclei such as the ventrobasal complex.
      To this aim, the delivery of the retrograde neuroanatomical tracer Fluoro-Gold
      into the caudal caudate putamen resulted in the appearance of retrogradely
      labeled neurons in the ventral posteromedial and ventral posterolateral thalamic
      nuclei. These projections were further confirmed with injections of the
      anterograde tracers biotinylated dextran amine or Phaseolus vulgaris
      leucoagglutinin into these thalamic nuclei, by showing the existence of axonal
      terminal fields located in the caudal striatum. These results support the
      existence of direct projections linking the thalamic ventrobasal complex and the
      caudal striatum in the rat, probably via collateralization of thalamocortical
      axons when passing through the caudate putamen, and therefore supporting the
      putative involvement of the caudal striatum in sensory-related functions.

PMID- 11455445
TI  - High level Purkinje cell specific expression of green fluorescent protein in
      transgenic mice.
AB  - The green fluorescent protein (GFP) has become a powerful tool in molecular and
      cell biology. It is a commonly used marker for cloning and transfection
      experiments as well as a useful label of living cells allowing continuous
      observation of developing structures. In order to unravel mechanisms of neuronal
      differentiation, we generated a transgenic mouse model which expresses GFPS65T,hu
      under the control of the Purkinje cell-specific promoter L7/pcp-2. Here, we show
      that GFPS65T,hu is highly expressed specifically in the cerebellum in whole mount
      preparations after the 2nd postnatal week. GFPS65T,hu can be detected exclusively
      in Purkinje cells of cerebellar slices. The fluorescence intensity of GFPS65T,hu
      should enable the characterization and recording of axons, dendrites, and spines
      protruding from these neuronal processes. The level of GFP expression can be
      quantified by western blotting which allows to analyze protein expression and
      L7/pcp-2 promoter regulation in vivo. The application of cellular and
      physiological techniques on L7GFP mice will provide a remarkable opportunity to
      investigate various aspects of neuronal development at the cellular and
      subcellular levels.

PMID- 11455446
TI  - Ultrastructural localization of basigin in normal human epidermis.
AB  - Basigin is a glycosylated transmembrane protein belonging to the immunoglobulin
      superfamily. It is thought to play roles in intercellular recognition involved in
      cell differentiation. We previously demonstrated at the light microscope level a
      correlation between basigin expression and epidermal differentiation. In the
      present study, the ultrastructural localization of basigin in normal human
      epidermal keratinocytes was investigated by immunoelectron microscopy. The
      basigin labeling was strongest on membranes of basal cells, weaker on prickle
      cells, and absent in granular and horny cells. On the membrane of basal cells,
      labeling was observed on the apical and lateral sides but not on the dermal side.
      Gold particles were mostly observed on the surface of microvilli, especially on
      their tips. There were fewer on the intermicrovillous membrane and they were
      absent on the desmosome. These results are consistent with our previous report
      that basigin expression is correlated with differentiation of epidermal
      keratinocytes. Microvilli on basal and suprabasal keratinocytes might play roles
      in the differentiation of keratinocytes through basigin on the tips of
      microvilli.

PMID- 11455447
TI  - A monoclonal antibody against the glutaraldehyde-conjugated polyamine,
      putrescine: application to immunocytochemistry.
AB  - We developed a mouse monoclonal antibody (mAb; APUT-32, IgG1 subisotype mAb)
      against putrescine (Put) conjugated to bovine serum albumin using a
      glutaraldehyde (GA)-sodium borohydride procedure, for applications in
      immunocytochemistry (ICC). The antibody specificity was evaluated by an ELISA
      binding test, simulating the ICC of tissue sections. APUT-32 mAb was highly
      specific to Put, and distinguished alterations in the chemical structure of other
      polyamine (PA) analogs, showing 3.8% crossreaction with cadaverine, 3.3% with
      spermidine (Spd), and 2.3% with 1,3-diaminopropane. Comparable results in
      immunoreactivity of APUT-32 mAb were obtained with the ELISA inhibition test. By
      the indirect immunoperoxidase method using the APUT-32 mAb, Put-like
      immunoreactivities were observed in the cytoplasm of HeLa and MCF-7 cell lines
      fixed with GA in combination with NaBH4 reduction, but almost no immunoreaction
      was seen in the cytoplasm of the human melanoma BD cell line. On the other hand,
      the same method but using a previously prepared ASPM-29 mAb, specific for
      spermine (Spm) and Spd, produced intense immunostaining in the cytoplasm of all
      the three cell types. The Put-like immunoreaction was completely abolished by
      absorption of the APUT-32 mAb with 10 microg/ml Put-human serum albumin conjugate
      prepared using GA and NaBH4. HPLC analysis was also performed for the levels of
      each of the PAs in the three types of cell, showing that the levels of Put
      detected were much lower than those of Spm and Spd, and were strikingly different
      in the three cell lines among which the human melanoma BD cell line contained the
      lowest levels of Put. These results strongly suggest that APUT-32 mAb reacts
      specifically with Put in the tumor cells and therefore has the potential as a new
      tool for elucidating the biological roles of Put in cells and tissues.

PMID- 11455448
TI  - Expression of connexin 37, 40, and 43 mRNA and protein in renal preglomerular
      arterioles.
AB  - Gap junctions allow direct intercellular coupling between many cells including
      those in the vascular wall. Studies of connexin expression in cells of the
      microcirculatory system are very few in number. However, cell-to-cell
      communication between cells of the arteriolar wall may be particularly important
      in microcirculatory control. We investigated the expression of connexins 43, 40,
      and 37 (Cx43, Cx40, Cx37) mRNA and proteins in primary cultures of smooth muscle
      cells (SMC) from rat renal preglomerular arterioles and in the aortic cell line
      A7r5. Furthermore protein expression in preglomerular arterioles in frozen
      sections was evaluated. SMC were isolated from kidneys using an iron oxide sieve
      method and explant technique. Total RNA from these cultures was tested by RT-PCR
      analysis for the expression of the three connexins mRNA. Using immunofluorescence
      we examined whether the expression pattern of connexin protein in the cell
      culture and frozen sections corresponded to the mRNA expression. The data show
      that A7r5 and preglomerular SMC express mRNA for Cx37 in addition to Cx43 and
      Cx40. In A7r5 cells the mRNA for Cx43, Cx40, and Cx37 are translated to protein,
      whereas cultured preglomerular SMC and the media of afferent arterioles in frozen
      sections only showed Cx40 immunoreactivity.

PMID- 11455449
TI  - Expression of an immediate early gene, IEX-1, in human tissues.
AB  - IEX-1 is an immediate early gene that is induced by ionizing radiation,
      ultraviolet radiation, and a variety of growth factors. It plays an important
      role in the regulation of cellular growth. Earlier, we performed studies on the
      distribution of IEX-1 messenger RNA in different tissues and on the subcellular
      localization of IEX-1 protein. No reports, however, have appeared concerning the
      distribution of IEX-1 protein in a variety of human tissues. We raised a
      polyclonal antibody against a synthetic IEX-1 peptide (amino acids 51-75) and
      used the antibody to study the distribution of the protein in human tissues. We
      demonstrate that IEX-1 is strongly expressed in epithelia of the skin, trachea,
      gastrointestinal, and genitourinary systems, as well as in the pancreas and
      breast. Endothelial cells within the vasculature of most tissue/organs also
      strongly express IEX-1. Liver, lung, lymph nodes, and placenta stain weakly. No
      IEX-1 epitopes were detected in the thymus, testes, ovary, myocardium, skeletal
      muscle, or spleen. We conclude that IEX-1 is widely expressed in epithelial and
      endocrine tissues, as well as in vascular endothelium.

PMID- 11455450
TI  - Localization of mRNAs encoding peroxisomal proteins in cell culture by non
      radioactive in situ hybridization. Comparison of rat and human hepatoma cells and
      their responses to two divergent hypolipidemic drugs.
AB  - A non-radioactive in situ hybridization (ISH) protocol for localization of mRNAs
      encoding peroxisomal proteins in hepatoma cell lines from humans (HepG2) and rats
      (MH1C1) is presented. In comparison to a similar procedure reported for tissue
      sections, the cell culture preparations require only brief fixation in 4%
      paraformaldehyde and their permeabilization is achieved by a very low
      concentration (1 microg/ml) of proteinase K. The exclusive localization of
      transcripts in the cytoplasm of hepatoma cells with the absence of nuclear
      staining and the completely negative sense controls confirm the specificity of
      the method. The marked differences in signal intensity between the results of
      albumin and beta-actin mRNAs which are of high abundance in contrast to moderate
      to low abundance of peroxisomal mRNAs show the high sensitivity and the wide
      range of applicability of our protocol. This is also confirmed by divergent
      results of treatment of hepatoma cell lines with clofibrate and cetaben on mRNA
      levels of catalase and acyl-CoA oxidase. The ISH results of drug treatment of
      cell lines are confirmed also by slot blot analysis of total RNA extracts using
      32P-labeled probes. Thus the protocol presented here provides a sensitive tool
      for ISH localization of mRNAs encoding peroxisomal proteins. In combination with
      immunocytochemistry it may be useful to monitor intercellular differences in
      expression levels of specific mRNAs in correlation with the abundance of
      structurally divergent forms of peroxisomes (tubular versus spherical) and their
      importance in the biogenesis of peroxisomes.

PMID- 11455451
TI  - Cetaben-induced changes on the morphology and peroxisomal enzymes in MH1C1 rat
      hepatoma cells and HepG2 human hepatoblastoma cells.
AB  - Human HepG2 and rat MH1C1 hepatoma cell lines were examined for their response to
      cetaben, an exceptional type of peroxisome proliferator. Shape change and
      proliferation of peroxisomes as well as induction of selected peroxisomal enzymes
      catalase, acyl-CoA oxidase, and peroxisomal bifunctional enzyme, were assessed in
      response to cetaben. In MH1C1 cells, peroxisomes were seen in clusters displaying
      typical features of microperoxisomes. Cetaben caused little but reversible
      proliferation and morphological heterogeneity with the occurrence of dumbbell
      shaped and cup-shaped peroxisomal profiles. Peroxisomes in HepG2 cells showed
      marked variation in size and shape. Cetaben treatment of HepG2 cells caused
      disintegration of Golgi regions and augmented mitochondrial matrix.
      Interestingly, MH1C1 cells showed different subunit composition of acyl-CoA
      oxidase in immunoblot analysis: only subunit A at 72 kDa was detected but not the
      cleavage products. In situ hybridization underlined the marked morphological
      heterogeneity observed, and both cell lines revealed different stages of gene
      expression. Our results indicate that cetaben represents an extraordinary type of
      peroxisomal proliferator with pleiotropic effects on human and rat hepatoma
      cells, and, at least in the human hepatoma cell line HepG2, these effects are not
      restricted to peroxisome proliferation.

PMID- 11455452
TI  - Immunohistochemical localization of estrogen receptor-alpha in sex ducts and
      gonads of newborn piglets.
AB  - Estrogen receptor-alpha (ER-alpha) expression in piglet uteri has previously been
      reported from day 15 after birth. Nevertheless, uterine tissue has been reported
      to be estrogen sensitive from the day of birth. Since estrogen action in the
      uterine tissue is suggested to be mediated principally by ER-alpha, the present
      study aimed to evaluate the presence of ER-alpha in uteri of 1- to 2-day-old
      piglets by means of immunohistochemistry. In addition, sex ducts and gonads of
      both sexes were examined. The results clearly demonstrate the presence of ER
      alpha immunopositive cells in uterine tissue, which explains its estrogen
      responsiveness. Immunostaining was most intense in the glandular epithelial cells
      and is suggested to indicate participation of ER-alpha in adenogenesis. In
      oviducts, almost all epithelial cells were immunostained moderately positive,
      while the stroma cells were stained comparably more positive. The functional
      significance of this intensity difference is uncertain but could indicate that
      part of the estrogen action on the epithelium is mediated through the stroma
      cells, as is known for the uterus. In ovaries, the surface epithelium and stroma
      cells were immunostained, whereas germ and granulosa cells were immunonegative.
      It is speculated that ER-alpha might be involved in yet unknown intraovarian
      mechanisms. In male sex ducts, immunostaining was virtually confined to the
      epithelium of efferent ducts. All cells in the epididymis as well as in vas
      deferens were immunonegative. The unique presence of ER-alpha in efferent ducts
      corresponds with localization in other species, where it has been shown to be
      involved in fluid reabsorption. The obtained data on localization of ER-alpha
      correspond with the present knowledge, obtained in ER-alpha knockout mice, of the
      biological function of ER-alpha within male and female gonads and sex ducts.

PMID- 11455453
TI  - Guanylin and uroguanylin in the parotid and submandibular glands: potential
      intrinsic regulators of electrolyte secretion in salivary glands.
AB  - The intestinal peptides guanylin and uroguanylin regulate the electrolyte/water
      transport in the gastrointestinal epithelium via activation of cystic fibrosis
      transmembrane conductance regulator (CFTR), the cystic fibrosis gene product.
      Because a major but incompletely understood function of the salivary glands is
      the CFTR-mediated secretion of an electrolyte-rich fluid, we investigated the rat
      and guinea pig parotid and submandibular glands for expression, cellular
      distribution, and subcellular localization of guanylin and uroguanylin. RT-PCR
      analyses with guanylin and uroguanylin-specific primers revealed that both
      peptides are highly expressed in the parotid and submandibular glands. At the
      translational level, western blotting analyses with peptide-specific guanylin and
      uroguanylin antibodies identified the expected 12.5-kDa immunoreactive peptides
      in these organs. At the cellular level, guanylin and uroguanylin were exclusively
      confined to epithelial cells of the intralobular and interlobular ducts. At the
      subcellular level, the immunoreactivities were localized by preembedding
      immunoelectron microscopy to small vesicles which were concentrated at the apical
      part of the secretory epithelial cells. The expression and cell-specific
      localization of guanylin and uroguanylin in the salivary glands indicate that
      these peptides may be specifically involved in the regulation of CFTR-mediated
      electrolyte/water secretion in the salivary gland ductal system.

PMID- 11455465
TI  - Adjuvant therapies using biliary stenting for malignant biliary obstruction.
AB  - The aim of this study was to analyze the patency of expandable metallic stents in
      malignant biliary obstruction and to evaluate the efficacy of adjuvant therapy
      accompanied by biliary stenting. We analyzed 29 patients in whom bile duct
      stenting was performed for malignant biliary obstruction. Their types of disease
      were: hilar ductal carcinoma (n = 8), gallbladder carcinoma (n = 11), and
      pancreatic carcinoma (n = 10). Initially, 46 expandable metallic stents were
      placed in 29 patients. In 23 of the 29 patients, adjuvant therapy was
      administered. Seventeen patients underwent radiotherapy, and 16 patients received
      various systemic chemotherapies. In principle, hyperthermia was performed twice a
      week, simultaneously with radiotherapy. Patient survival and the probability of
      stent patency were calculated using actuarial life table analysis. There was no
      significant difference in stent patency among the patients according to type of
      disease. Hyperthermia did not influence the stent patency rate. The median stent
      patency time was significantly greater in the chemo-radiation group than in the
      no-adjuvant therapy group: 182 days versus 68 days, respectively (P = 0.017).
      Moreover, a significant increase was seen in the median survival time in the
      chemo-radiation group: 261 days versus 109 days (P = 0.0337). Complications
      occurred in 9 patients (31.0%). Stent occlusion occurred in 6 patients (20.7%),
      with all of these patients managed successfully using a transhepatically placed
      new expandable metallic stent, employing the stent-in-stent method. Stent
      migration occurred in 2 patients after radiotherapy. Adjuvant therapies such as
      radiotherapy and systemic chemotherapy, in combination with stent insertion,
      resulted in an increase in the patency period of expandable metallic stents and
      in increased patient survival time.

PMID- 11455466
TI  - Role of endoscopic endoprostheses in proximal malignant biliary obstruction.
AB  - The management of hilar strictures is dependent upon their resectability and may
      therefore require a multidisciplinary approach. However, resectability rates for
      such tumors are reported to be in the region of 15%-20%, and, therefore,
      palliative therapy will be the mainstay of treatment for most patients. With the
      presenting symptoms being those of obstructive jaundice and the consequences of
      cholestasis, a significant improvement in morbidity can be obtained by achieving
      biliary drainage. A number of options are available, including the placement of
      Teflon or expandable metallic endoprostheses by either the endoscopic or
      percutaneous route. Some considerable debate exists as to which route of stent
      placement is best, and in many circumstances the decision will depend on the
      availability of local services. Some have suggested that success rates with
      percutaneous stenting are superior to those for endoscopic placement, but the
      latter technique may be associated with fewer complications. In competent hands,
      endoscopic placement does achieve a high rate of success and it should be
      remembered that a combined approach may further improve success rates. The debate
      over the use of plastic versus metallic stents is centered around the higher
      rates of stent occlusion/migration for plastic stents seen in some studies,
      although a stent change is usually possible. An additional advantage of metallic
      stents is that they may provide drainage of the side branches of the biliary tree
      through the mesh. However, possible drawbacks may be a greater difficulty in
      placement of a second stent where a first provides inadequate drainage, and cost
      issues often have to be taken into consideration. Considerable debate exists over
      the optimum number of stents required to achieve adequate drainage and minimize
      the risks of cholangitis. There is good evidence that if overfilling of the
      biliary tree with contrast is avoided with only the segments to be drained
      visualized, a single stent may be all that is required, while others argue that
      placement of more than one stent may improve survival. In the following review we
      discuss these issues, and conclude by considering success rates and complications
      following endoprosthesis insertion; we also discuss the prognosis of patients
      treated in this way.

PMID- 11455467
TI  - Intrahepatic cholangiojejunostomy for unresectable malignant biliary tumors with
      obstructive jaundice.
AB  - We reviewed our experience with intrahepatic cholangiojejunostomy as a palliative
      therapy for patients with unresectable malignant diseases involving the ductal
      confluence or the common hepatic duct. Fifteen patients with malignant biliary
      obstruction were treated by cholangiojejunostomy at our hospital. Two patients
      had intrahepatic cholangiocarcinoma, 7 had gallbladder carcinoma, 5 had bile duct
      carcionoma, and 1 had pancreatic carcinoma. Segment III cholangiojejunostomies
      were performed in 14 patients and segment V cholangiojejunostomy in 1.
      Contraindications for surgical resection were locoregional invasion of tumors
      involving the proper and/or common hepatic artery and portal vein in 15 patients
      and the presence of hepatic metastases in 6 patients. Liver metastases were
      detected in 5 of the 7 patients with gallbladder carcinoma. Postoperative
      complications occurred in 2 patients (13%), but there was no leakage of the
      cholangioenteric anastomosis in our series. There was no operative mortality
      after cholangiojejunostomy. Of the 9 patients who survived for more than 6 months
      after surgery, 7 showed a significant improvement in performance status (PS) (82
      +/- 10%) 3 months after the surgery compared with the preoperative PS (70 +/-
      7%). Four of the 9 patients had recurrent cholangitis as a late complication, but
      4 were completely free from jaundice. Median survival after cholangioenteric
      bypass was 9 months (range, 2-25 months). With respect to tumor location, the
      median survival time was 4 months (range, 2-25 months) in patients with
      gallbladder carcinoma and 15.5 months (range, 12-22 months) in those with bile
      duct carcinoma. While the median survival period after surgery was only 3 months
      (range, 2 to 8 months) in the 5 patients with hepatic metastases from gallbladder
      carcinoma, 2 patients without liver metastasis survived for 9 and 25 months after
      segment III cholangioenteric bypass. In conclusion, cholangiojejunostomy can
      provide useful palliation for malignant biliary obstruction when combined with
      careful patient selection.

PMID- 11455468
TI  - Radiotherapy as a component of multidisciplinary treatment of bile duct cancer: a
      surgeon's perspective.
AB  - Surgery is the only curative treatment for bile duct cancer (BDC). However,
      because of frequent loco-regional recurrence, radical surgery during advanced
      stages of the disease is often unsuccessful. Despite recent evidence of
      improvement in patient survival and quality of life, alternatives such as
      radiation therapy have not been fully developed and remain controversial. This
      article reviews current publications that deal with various irradiation
      procedures for the treatment of BDC, with particular attention to adjuvants to
      surgical resection, including liver transplantation, as a component of treatment
      of BDC. Specialized boost techniques, including conformal external beam
      irradiation (EBRT), brachytherapy via transhepatic catheters or a retrograde
      endoscopic stent, or intraoperative irradiation with electrons (IOERT), are
      summarized in relation to patient survival.

PMID- 11455469
TI  - Photodynamic therapy for cholangiocarcinoma.
AB  - The prognosis of nonresectable cholangiocarcinoma is dismal, and in Bismuth type
      III and IV tumors relief of jaundice is seldom achieved, despite successful
      endoprosthesis insertion. Therefore, we evaluated additional photodynamic therapy
      in patients who failed to respond to endoprostheses insertion. All patients
      showed good clinical results in regard to jaundice, quality of life; and survival
      time (median, 439 days). Before initiating a randomized multicenter trial we
      wanted to evaluate these preliminary results in a greater number of patients.
      Twenty-one patients underwent photodynamic therapy in addition to endoscopic
      drainage. The hematoporphyrin derivative Photofrin was infused intravenously (2
      mg/kg body weight), and intraluminal photoactivation was performed 2 days later.
      Bilirubin decreased from a mean level of 201.26 +/- 189.25 micromol/l after
      stenting alone to 68.87 +/- 78.27 micromol/l (P = 0.0051), and the Karnofsky
      index improved from 49.04% +/- 28.79% to 72.85 +/- 19.01 (P = 0.003). Thirteen
      patients have died and 8 patients are still alive, with a follow-up period of 82
      739 days. The 6-month survival time is 95%. Similar results were obtained by
      another group, with 75% overall (stage M1 and M0) survival after 6 months and
      beyond 80% for stage M0. Other authors treated 7 patients and saw a remarkable
      reduction of bile duct stenosis and bilirubin decrease in all patients.

PMID- 11455470
TI  - Prevention of severe change in acute pancreatitis: prediction and prevention.
AB  - Bacterial infection of pancreatic necrosis is the most frequent local
      complication of severe acute pancreatitis and is responsible for the majority of
      deaths in this disease. The development of systemic complications of severe acute
      pancreatitis such as septic multiple organ failure is closely related to infected
      necrosis. In this review, the factors predisposing to a severe course of acute
      pancreatitis are discussed as are clinical and laboratory markers which allow
      identification of patients at risk. Prevention of complications of acute
      pancreatitis is difficult. A variety of drugs including antiproteases and
      antiinflammatory agents have been shown to be of no benefit with regard to the
      reduction of severe complications. At present, based on the results of controlled
      trials, there is the widespread belief that prophylactic antibiotics are capable
      of reducing the incidence of infected pancreatic necrosis. New approaches for the
      prevention of systemic complications of severe acute pancreatitis are total
      enteral nutrition and local arterial infusion of antibiotics and antiproteases
      into the celiac trunk.

PMID- 11455471
TI  - Ventral margin of the paracaval portion of human caudate lobe.
AB  - The topographic anatomy of the ventral margin of the caudate lobe of the human
      liver is still obscure. We hypothesized the existence of a "precaudate plane", as
      a flat or slightly curved plane defined by the ventral margins of both the
      ligamentum venosum and hilar plate. Using 61 cadaveric liver specimens, without
      great differences in external shape or significant variations in the hilar
      bifurcation, we examined whether the paracaval caudate branches (PCs) ran through
      the plane to the ventral side. In 22 of the 61 specimens (36.1%), the PC extended
      over the plane for less than 10 mm (10 specimens), for 10-20 mm (7 specimens), or
      for more than 20 mm (5 specimens). The ventral extension consistently included
      the dome-like area under the terminals of the middle and right hepatic veins.
      Therefore, the ventrally extended PCs often interdigitated with these veins and
      their tributaries. The ventral extension often reached the upper, diaphragmatic
      surface. However, several branches were too difficult to discriminate from the
      PC, especially those with morphologies intermediate between the PC and segmental
      portal branches to S4 or S2. We discuss how to identify and manage the ventrally
      extended PCs before and during surgery.

PMID- 11455472
TI  - Recurrence after surgical resection of intrahepatic cholangiocarcinoma.
AB  - We aimed to assess the patterns of recurrence after surgery for intrahepatic
      cholangiocarcinoma (ICC) and the outcomes of treatment in patients with
      recurrence. From 1981 to 1999, 123 patients with ICC underwent hepatectomy. The 3
      year and 5-year survival rates were significantly higher in patients after
      curative resection (n = 56; 53%, 50%) than in patients after noncurative
      resection (n = 67; 7%, 2%; P < 0.0001). In 54 patients followed-up after curative
      resection, the rate of recurrence after surgery was 46%. The recurrences were in
      the liver (56%), abdomen (disseminated; 24%), and lymph nodes (20%). The rates of
      recurrence were significantly higher in patients with various classifications of
      mass-forming ICC tumors (P = 0.039) than in those with other types of tumors, and
      in patients with tumors over 3 cm in greatest diameter than in those with tumors
      3 cm or less (P = 0.006). Hepatic recurrence, abdominal dissemination, and
      intraductal recurrence were significantly related to tumors that included mass
      forming ICC (P = 0.002), tumors that included periductal infiltrating ICC (P =
      0.009), and tumors that included intraductal growth ICC (P = 0.038),
      respectively. Seven patients with recurrence underwent radiation, chemotherapy,
      immunotherapy, or surgical resection. Only 2 patients, with intrahepatic
      metastasis and intraductal recurrence, respectively, had good outcomes after
      surgery. The effectiveness of other treatments has not been established.

PMID- 11455473
TI  - Comparison of laparoscopic versus open cholecystectomy in patients with cardiac
      valve replacement.
AB  - To evaluate the benefits and safety of laparoscopic cholecystectomy (LC) in
      patients with cardiac valve replacement (which frequently leads to
      cholelithiasis), 12 patients with cholelithiasis associated with cardiac valve
      replacement were studied. The patients were divided into two groups, of 6
      patients each, according to the type of operation performed, open cholecystectomy
      (OC) or LC. The postoperative course was monitored with respect to laboratory
      data on postoperative days (POD) 1, 3, and 7. The mean duration of operation,
      blood loss, days to food resumption, length of hospital stay, and morbidity were
      compared between the two groups. Significant differences (P < 0.05) were found
      between the OC and LC groups in white blood cell counts on POD 1 (12 980 +/-
      3040/mm3 vs 8300 +/- 1590/mm3), days to food resumption (2.7 +/- 0.4 days vs 1.0
      +/- 0.7 days), and length of postoperative stay (15.8 +/- 1.0 days vs 10.8 +/-
      1.6 days). There were no complications in the LC group, but 1 patient in the OC
      group had heart failure postoperatively. Our findings indicate the efficacy and
      safety of LC in patients with cardiac valve replacement.

PMID- 11455474
TI  - Hemodynamic patterns of phosphatidylcholine hydroperoxide and hyaluronic acid
      during hepatic ischemia-reperfusion.
AB  - We investigated the hemodynamic pattern of serum hyaluronic acid (HA) and
      compared it with that of plasma phosphatidylcholine hydroperoxide (PCOOH) in
      terms of a convenient parameter of reperfusion injury. Using pig models, we
      designed two continuous ischemia groups, prepared by blockage of the blood flow
      at the hepatic hilum for 10 or 30 min. A discontinuous ischemia model was
      prepared by repeating the 10-min ischemia procedure, followed by 10 min of
      reperfusion, to a total ischemia period of 30 min. The PCOOH level started to
      increase just after reperfusion and reached the peak at 90 min, followed by a
      gradual decline after 6 h. The HA level increased rapidly in the continuous
      ischemia groups, starting immediately after ischemia onset until immediately
      before reperfusion, followed by a gradual decrease during up to 6 h of
      reperfusion. The HA levels in the three groups were almost normalized after 90
      min of reperfusion, when the PCOOH level reached the peak. These results
      indicated that the plasma PCOOH level is a useful parameter for predicting the
      onset and progress of reperfusion injury in its initial stages.

PMID- 11455475
TI  - Primary sclerosing cholangitis successfully treated by resection of the
      confluence of the hepatic duct.
AB  - Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by
      chronic inflammatory fibrosis of the extra- and intrahepatic bile ducts. Although
      the prognosis of patients with PSC was believed to be poor, some patients have
      not experienced the expected rapid clinical progression. A 51-year-old man with
      PSC was initially hospitalized for jaundice. Laboratory data showed low levels of
      the complement components C3, C4, and CH50. Percutaneous transhepatic biliary
      drainage was performed. Cholangiography revealed complete obstruction of the
      common bile duct below the confluence of the cystic duct. The confluence of the
      hepatic duct was resected and it was reconstructed by hepaticojejunostomy for
      palliation of the obstructive jaundice. Increased thickness of the walls of the
      common bile duct, right hepatic bile duct, and gallbladder was observed.
      Histopathological examination of the resected specimen revealed periductal
      fibrosis, with an onion-skin-like appearance. The patient is currently doing
      well, approximately 7 years after the surgery, without any signs of PSC
      recurrence. In this extraordinary patient, the laboratory data for C3, C4, and
      CH50 showed a complete return to normal levels. The positive results in this
      patient suggest that resection of the confluence of the hepatic duct may be an
      effective surgical treatment for noncirrhotic PSC patients who have dominant
      extrahepatic strictures.

PMID- 11455476
TI  - A repeated pancreatectomy in the remnant pancreas 22 months after pylorus
      preserving pancreatoduodenectomy for pancreatic adenocarcinoma.
AB  - We report a case of a repeated curative pancreatic resection in the remnant
      distal pancreas 22 months after pylorus-preserving pancreatoduodenectomy (PpPD).
      The patient was a 52-year-old woman with a past history of PpPD for
      adenocarcinoma of the head of the pancreas 22 months prior to the present
      operation. The original tumor was histopathologically diagnosed as a papillary
      adenocarcinoma with clear surgical margin at the surgical cut end of the pancreas
      (R0, International Union Against Cancer [UICC] classification). Twenty months
      after the PpPD, a follow-up computed tomography (CT) scan showed multiple low
      density lesions in the body and tail of the pancreas without any other distant
      metastasis. A second operation, curative resection of the remnant pancreas, with
      splenectomy and distal gastrectomy, was performed. The second tumor was a
      papillary adenocarcinoma, the same diagnosis as that of the first tumor, and it
      also showed similar histopathological findings, including immunohistochemical
      staining of Ki-67 and p53 protein, and the same pattern of K-ras point mutation.
      The patient is considered to have shown a rare, unique pancreatic cancer with
      metachronous carcinogenesis in the remnant pancreas.

PMID- 11455477
TI  - Periampullary choledochoduodenal fistula in ampullary carcinoma.
AB  - Most patients with ampullary carcinoma have obstructive jaundice without
      cholangitis. We experienced a patient with ampullary carcinoma who presented with
      obstructive jaundice and cholangitis, probably because of an accompanying
      periampullary choledochoduodenal fistula. A 77-year-old Japanese man had
      jaundice, high fever, and upper abdominal pain and was diagnosed, at another
      hospital, with obstructive cholangitis. On admission to our hospital, his
      symptoms and signs had subsided spontaneously. Abdominal ultrasonography showed
      cholecystolithiasis and dilatation of the common bile duct. Duodenoscopy showed
      an ulcerating tumor at the oral prominence of the ampulla of Vater and a
      periampullary choledochoduodenal fistula at the bottom of the ulcer. Biopsy from
      the fistula showed well differentiated adenocarcinoma. With a diagnosis of
      ampullary carcinoma with fistula formation, the patient underwent pylorus
      preserving pancreatoduodenectomy. The diagnosis was confirmed by histology. This
      communication presents a unique case of ampullary carcinoma that caused
      obstructive jaundice, which subsided spontaneously but was associated with
      cholangitis caused by the divergent effects of the periampullary
      choledochoduodenal fistula formed by the carcinoma.

PMID- 11455478
TI  - Microcirculatory derangements in acute pancreatitis.
AB  - During the past decade, a considerable number of experimental studies have
      confirmed the hypothesis that microcirculatory derangements play a pivotal role
      in the pathogenesis of acute pancreatitis, including the process of conversion
      from edematous to necrotizing injury. Predominant microcirculatory disorders are
      nutritive capillary perfusion failure, with the consequence of prolonged focal
      hypoxia or anoxia, and inflammation-associated microvascular leukocyte
      recruitment, CD11b- and intercellular adhesion molecule (ICAM)-1-mediated
      leukocyte-endothelial cell interaction and loss of endothelial integrity, which
      may result in both edema formation and necrosis. A variety of proinflammatory
      mediators, such as oxygen radicals, leukotrienes, platelet-activating factor, and
      interleukins, but also bradykinin and endothelins, seem to be involved in
      triggering the manifestations of these microcirculatory disorders. In contrast,
      the anti-inflammatory interleukin-10, as well as nitric oxide, are thought to be
      capable of protecting from these pancreatitis-associated microvascular injuries.
      This knowledge may be encouraging for the development of novel therapeutic
      strategies, aiming at the attenuation of microcirculatory disorders, and, thus,
      preventing tissue injury in acute pancreatitis.

PMID- 11455479
TI  - Cytokine modulation in acute pancreatitis.
AB  - The clinical manifestations of acute pancreatitis (AP) vary significantly from
      mild to lethal in form, the severity of the disease being largely determined by
      the actions of various kinds of inflammatory mediators, including cytokines,
      reactive oxygen species, proteolytic enzymes, and lipids, as well as gaseous
      mediators. Despite increasing knowledge implicating the involvement of cytokines
      in the progression of AP, no clinical trials pertaining to cytokine modulation
      have been performed so far. Progress in intensive care technologies has
      contributed to the improvement of mortality and morbidity rates in severe AP in
      the past decade; however, it appears to be reasonable for clinicians to "line up
      their sights" on the modulation of cytokines as a direct treatment. In contrast
      to the large body of experimental studies demonstrating the beneficial effects of
      cytokine modulation on the amelioration of the disease, direct extrapolation from
      these successful experiments to the clinical situation seems to be extremely
      difficult.

PMID- 11455480
TI  - Management of acute pancreatitis: results of a 15-year experience in Taiwan.
AB  - In the past two decades, there have been great changes regarding the policy for
      treating acute pancreatitis. The aim of this study was to examine the
      chronological changes in the management of acute pancreatitis in a tertiary
      referral center. A retrospective review was carried out of the management
      approaches for acute pancreatitis in the 15 years since 1984. The patients were
      divided into groups according to the admission date, representing two periods:
      period 1, from 1984 through 1992; and period 2, from 1993 through 1999. Decision
      making for treating acute pancreatitis was based mainly on Beger's criteria. The
      background features and treatment outcome were compared between the two periods.
      The severity of pancreatitis was based on the Atlanta classification system.
      Octreotide was available from January 1993. No differences could be found between
      the two periods regarding the patients' background characteristics or severity of
      pancreatitis. Patients in period 2 had a longer interval between the onset of
      pancreatitis and surgery, and a lower incidence of pancreatectomy. Although the
      surgical morbidity, mortality, and reoperation rates were not significantly
      different between the two periods, more patients with severe acute pancreatitis
      in period 2 received nonsurgical treatment, and a lower mortality rate was also
      noted. With improvements in critical care, increasing experience, and better
      surgical techniques, even patients with severe acute pancreatitis can be treated
      by nonsurgical means. However, aggressive surgical intervention is necessary for
      patients who have signs of infected necrosis and whose disease is not
      controllable by conservative methods.

PMID- 11455481
TI  - Prophylaxis for septic complications in acute necrotizing pancreatitis.
AB  - Because the mortality of severe pancreatitis is higher when infected necrosis
      supervenes, prevention of infections has become a relevant endpoint for
      management. The "ideal" drug should be characterized by specific activity against
      the bacteria known to be responsible for infection and should be able to
      penetrate the gland in a sufficient concentration. To date there have been eight
      prospective trials with antibiotics, one on selective digestive decontamination,
      and others with enteral nutrition. A meta-analysis regarding experiences with
      antimicrobial drugs reports a significant reduction in the incidence of infected
      necrosis and pancreatic abscesses during severe pancreatitis. In conclusion,
      among the several options aimed at reducing infections during necrotizing
      pancreatitis, the prophylactic use of antibacterial drugs is the only one to have
      been tested to date in several randomized studies. Strong consideration should be
      given to treating patients with severe pancreatitis with broadspectrum
      antibiotics, selective digestive decontamination, and enteral nutrition.

PMID- 11455482
TI  - Continuous regional arterial infusion (CRAI) therapy reduces the mortality rate
      of acute necrotizing pancreatitis: results of a cooperative survey in Japan.
AB  - We evaluated the usefulness of continuous regional arterial infusion (CRAI) of
      protease inhibitors and antibiotics in 156 patients with acute necrotizing
      pancreatitis (ANP) collected in a cooperative survey carried out in 1997 in
      Japan. The overall mortality rate was 18.6%, and the frequency of infected
      pancreatic necrosis was 12.8%. There was no significant difference in mortality
      rates between patients who received the protease inhibitor via CRAI and the
      antibiotics intravenously (group A) and patients who received both the protease
      inhibitor and the antibiotics via CRAI (group B), but the frequency of infected
      pancreatic necrosis was significantly lower in group B (7.6%) than in group A
      (23.5%). The mortality rate in patients in whom CRAI therapy was initiated within
      48 h after the onset of ANP (11.9%) was significantly lower than that in patients
      in whom CRAI therapy was initiated more than 48 h after the onset (23.6%). These
      results suggested that CRAI of both protease inhibitors and antibiotics was
      effective in reducing mortality and preventing the development of pancreatic
      infection in ANP when initiated within 48 h after the onset of ANP.

PMID- 11455483
TI  - Laparoscopic necrosectomy for acute necrotizing pancreatitis.
AB  - Severe acute pancreatitis (SAP), a disease state that is often complicated by an
      intricate pathologic process, has remained difficult to manage and is associated
      with high morbidity and mortality rates. Approximately 80% of patients have a
      mild form of the disease, while the other 20% develop a severe life-threatening
      form of the disease. These patients are at great risk for infection, multisystem
      organ failure, and, possibly, death. Necrotizing or infected pancreatitis
      requires a multimodal approach and often offers an indication for surgical
      intervention. The retroperitoneum of the patient with necrotizing pancreatitis
      should be treated as an abscess cavity, and drainage and debridement of all
      necrotic tissue should be performed. Over the past several decades, great
      achievements have been made in the treatment of the patient that presents with
      acute pancreatitis. However, the morbidity and mortality have remained high,
      according to recent literature. The laparoscopic era brings new alternatives in
      the surgical management of pancreatic diseases. Advances in laparoscopic
      technology and instrumentation allow the utilization of minimally invasive
      techniques, and lessen the stress of surgery in the already compromised
      pancreatitic patient.

PMID- 11455484
TI  - Surgical treatment of pancreatic cancer. Does extended lymphadenectomy provide a
      better outcome?
AB  - The rate of curative resection of pancreatic cancer has increased as a result of
      extended operations, but this has not led to any significant improvement in
      postoperative outcome. No definite conclusions were drawn in retrospective
      studies comparing outcome after standard and extended operations, and there was
      almost no difference in outcome between the two groups in a recent prospective
      randomized study. In addition, extended procedures are very stressful operations
      that, in most instances, impair the patient's quality of life (QOL). As a result,
      the need for performing extended surgery to treat pancreatic cancer has come into
      question. The outcome of advanced cancer in patients in whom curative resection
      cannot be achieved by extended operations is extremely poor, and we believe that,
      in such patients, priority should be given to QOL, by selecting bypass or limited
      operations instead. It is hoped that the value of extended surgery will be
      clarified by a very carefully planned multicenter prospective randomized study in
      the future.

PMID- 11455485
TI  - History of pancreaticojejunostomy in pancreaticoduodenectomy: development of a
      more reliable anastomosis technique.
AB  - The history of pancreaticojejunostomy in pancreaticoduodenectomy is described.
      Many types of operations have been devised in search of a more reliable method of
      anastomosis. To perform a safe and reliable pancreaticoenteric anastomosis it is
      necessary to understand the organ characteristics of the pancreas. We
      investigated factors required for a reliable pancreaticojejunostomy and devised a
      new surgical technique that meets those requirements. We introduce the
      theoretical substantiation and clinical usefulness of our new surgical technique
      while reviewing the history of pancreaticojejunostomy after
      pancreaticoduodenectomy. The unique aspect of our method is approximation of the
      pancreas stump and jejunal wall by six to eight interrupted sutures. It is
      speculated that too many sutures and tying too tight in the anastomosis may cause
      ischemia and necrosis of the pancreatic stump by restricting the tissue blood
      flow. Our method allows us not only to reduce the number of sutures, but also to
      avoid some of the complicated manipulations done in any other existing methods.
      The newly devised pancreaticojejunostomy is an excellent surgical technique with
      anastomotic failure seen in only two patients and no deaths out of 162
      consecutive patients.

PMID- 11455486
TI  - Blood supply to the duodenal papilla and the communicating artery between the
      anterior and posterior pancreaticoduodenal arterial arcades.
AB  - The communicating artery (ComA) between the anterior and posterior
      pancreaticoduodenal arterial arcades is little understood, although it has been
      described several times during the past 100 years. In 44 of 51 cadaveric
      specimens in the present study, the typical ComA was observed to pass between the
      major and accessory pancreatic ducts. In addition, a second ComA was sometimes
      found crossing inferior to the major pancreatic duct. The typical ComAs often (36
      of the 44) issued papillary branch(es). Although direct papillary branches of the
      posterior arcade were often observed to either coexist with (9 specimens) or
      exist independently (4 specimens), the ComA-derived branch seemed to be critical
      for papillary blood supply, because of its shorter length, greater thickness, and
      higher frequency. Moreover, the typical ComA could be a good landmark during
      limited pancreatic resection, such as duodenum-preserving subtotal resection of
      the pancreatic head or pancreatic segment resection, because the artery is likely
      to be an indicator of the borders between the celiac and superior mesenteric
      arterial territories, as well as those between the ventral and dorsal segments of
      the pancreas.

PMID- 11455487
TI  - Sugiura procedure in portal hypertensive children.
AB  - Bleeding from esophageal varices is an important cause of morbidity and mortality
      in children with portal hypertension. The treatment protocol is planned according
      to the etiologic factors underlying the portal hypertension, which may be either
      intrahepatic or extrahepatic. Although portasystemic venous shunt operations were
      common previously, they are now regarded as nonphysiologic and are rarely used
      because of their unexpected results and complications. Today, in many centers,
      endoscopic procedures have become the first-step treatment modality in bleeding
      esophageal varices. More complicated surgical procedures, such as
      devascularization procedures in extrahepatic portal hypertension, and liver
      transplantation in patients with failing liver, should be performed when
      conservative measures fail. We followed up 69 patients with portal hypertension
      with endoscopic sclerotherapy in our department. Here we present a retrospective
      evaluation of the effect of the Sugiura operation on the prognosis of 12 children
      (6 with extrahepatic and 6 with intrahepatic portal hypertension) who were not
      responsive to the sclerotherapy program. No rebleeding was seen in 9 of the 12
      (75%) patients after the procedure, and the mortality rate in this series was 1
      of 12 (8.3%); this patient died of hepatic failure.

PMID- 11455488
TI  - Anti-transforming growth factor-beta1 antibody transiently enhances DNA synthesis
      during liver regeneration after partial hepatectomy in rats.
AB  - The regulation of liver regeneration after partial hepatectomy (PHx) is complex
      and involves many different cytokines. We investigated the role of one of these,
      transforming growth factor-beta1 (TGF-beta1), an inhibitor of liver regeneration,
      in a Wistar male rat model, in which anti-TGF-beta1 antibody was injected
      immediately or 24 h after 70% PHx. Livers from treated animals contained an
      increased number of cells in S phase, according to 5-bromo-2'-deoxyuridine (BrdU)
      labeling 36 h after PHx. Antibody administration 24 h after PHx resulted in the
      highest peak of proliferation; moreover, peak MIB-5 labeling was also observed at
      that time. However, neither residual liver-weight-to-body-weight ratios nor
      regeneration rates differed significantly between any of the animals. Therefore,
      we also measured levels of serum TGF-beta1 and hepatocyte growth factor (HGF; an
      activator). With antibody administration at 0 or 24 h, TGF-beta1 levels were
      diminished at 24 or 36 h as compared with levels in control rats, but then
      rebounded, reaching a delayed peak at 48 or 72 h after PHx, respectively.
      Interestingly, there were also similar trends in HGF levels. These results
      indicate that TGF-beta1 may inhibit the G1 checkpoint, and serum TGF-beta1
      concentration may influence HGF to regulate liver regeneration and to maintain
      homeostasis of proliferation after PHx.

PMID- 11455489
TI  - Induction of immediate early genes after partial hepatectomy in cholestatic
      liver.
AB  - The protein products of immediate early genes (IEGs) behave as transcriptional
      regulators and play an important role in the regulation of gene expression
      associated with liver cell proliferation and apoptosis. The aim of this study was
      to examine whether the transcription of IEGs was induced by obstructive jaundice
      during liver regeneration after 70% partial hepatectomy, and to examine their
      association with animal survival, cell proliferation, and apoptosis. Obstructive
      jaundice (OJ) was induced in rats by common bile duct ligation (CBDL), and 70%
      partial hepatectomy was performed 5 days after CBDL (OJ group). Changes in the
      induction of the IEGs, c-fos and c-jun, were compared between control and OJ
      groups in relation to survival before and after partial hepatectomy. Cell
      proliferation and apoptosis were evaluated by proliferating cell nuclear antigen
      (PCNA) immunohistological staining and by an in situ TdT-mediated d-UTP
      digoxigerin nick-end labeling (TUNEL) method. The 2-week survival in the OJ group
      (2/7) was significantly less that of the sham operation (control) group (7/7).
      Enhanced induction of IEGs was evident in the OJ group after partial hepatectomy
      compared with findings in the control group. The PCNA-labeling index (LI) in the
      OJ group was increased after partial hepatectomy, but only minimally, compared
      with that in control animals. Apoptotic cells appeared in bile ducts and
      surrounding hepatocytes after partial hepatectomy in the OJ group, although
      apoptotic cells were rare in the control group. IEG transcription does occur
      after partial hepatectomy in jaundiced liver but it is enhanced and sustained,
      and leads to apoptosis rather than leading to the efficient proliferation of
      hepatocytes.

PMID- 11455490
TI  - Viability of liver grafts from fasted donor rats: relationship to sinusoidal
      endothelial cell apoptosis.
AB  - Previous studies have shown that livers from fasted donors appear to tolerate
      long-term preservation better than livers from fed donors, but the mechanism is
      not clear. Some studies have shown that the apoptosis of sinusoidal endothelial
      cells (SEC) appeared to be a pivotal mechanism of ischemia/reperfusion injury in
      liver transplantation. The purpose of the present investigation was to evaluate
      the relation of SEC apoptosis to liver viability in rats after liver
      transplantation, comparing findings for fasted and fed donors. Wistar rats were
      used as donors and recipients. The fed group had access to solid feed and water
      ad libitum. The fasted group was allowed access only to water for 4 days prior to
      liver harvest. All rat livers were preserved with University of Wisconsin (UW)
      solution at 2 degrees C for 24 h. After preservation, the livers were
      orthotopically transplanted, and survival time was measured. Apoptosis was
      determined by in-situ staining for apoptotic cells, using a TdT-mediated dUTP
      digoxigenin nick-end labeling (TUNEL) assay and electron microscope (EM)
      examination separately. The 14-day survival rates after 24-h preservation were 0%
      (0/11) for recipients of livers from fed donors and 91% (10/11) for recipients of
      livers from fasted donors. There was no significant difference in the numbers of
      TUNEL-positive SEC after 24-h preservation between the two groups. However, at 6
      h after transplantation, the number of TUNEL-positive SEC was significantly
      higher in the fed group than in the fasted group. These results suggest that
      donor fasting decreases SEC apoptosis after reperfusion alone, and that this may
      be related to the protection of the liver graft from reperfusion injury.

PMID- 11455491
TI  - Recurrent hepatic portal venous gas in a patient with hemodialysis- dependent
      chronic renal failure.
AB  - We report a case of recurrent hepatic portal venous gas (HPVG). A 51-year-old
      woman who had been undergoing hemodialysis for 19 years was admitted with
      abdominal pain. Computed tomography (CT) scans revealed the presence of HPVG, and
      bowel necrosis was confirmed at operation. After 1 year, the abdominal pain
      recurred. CT scans on the second admission also revealed HPVG; however, an
      exploratory laparotomy was negative. Recurring presentation of HPVG in the same
      patient has not been described previously.

PMID- 11455492
TI  - Solitary pancreatic tuberculosis mimicking advanced pancreatic carcinoma.
AB  - A 40-year-old woman was referred for pancreatic head carcinoma invading the
      portal vein. The dichotomy between the radiological findings and the general
      condition of the patient, as well as the laboratory results (no evidence of
      cholestasis), cast doubt on the diagnosis. There was no history of tuberculosis.
      The chest radiograph revealed no pathological findings. The anatomic
      relationships of the lesion entailed a high risk of vascular injury if tissue
      biopsy were to be done; therefore, diagnostic laparotomy was performed. Biopsy
      revealed granulomas with caseous necrosis, consistent with tuberculosis. After 6
      months of antituberculosis treatment, the lesions had completely resolved.
      Tuberculosis should be considered in the differential diagnosis of pancreatic
      masses, particularly in regions where the disease is endemic. The condition
      usually resembles an advanced pancreatic tumor. Performing a biopsy of inoperable
      lesions and maintaining a reasonable skepticism in regard to the evaluation of
      operable lesions (attention to nonexclusive but helpful clues, such as young
      patient age, history of tuberculosis, absence of jaundice) will lead to the
      diagnosis in most patients. Diagnostic laparotomy may be required in a small
      subset of patients. The response to antituberculosis treatment is very favorable.
      The role of resection (e.g., pancreatoduodenectomy) is very limited.

PMID- 11455493
TI  - Living-donor liver transplantation for Caroli's disease with intrahepatic
      adenocarcinoma.
AB  - A 36-year-old woman who had Caroli's disease with refractory cholangitis and
      complicated intrahepatic cholangiocarcinoma was successfully treated with living
      donor liver transplantation. Preoperative computed tomography and ultrasonography
      showed a small nodule in the dilated intrahepatic bile duct. In the resected
      liver specimen, a small papillary tumor was located in the dilated intrahepatic
      bile duct of the right lobe. The pathological finding revealed a well
      differentiated papillary adenocarcinoma without invasion to the parenchyma. The
      patient is currently doing well 2.5 years after transplantation, with no signs of
      recurrence of the disease. For Caroli's disease, we believe we can achieve good
      results with liver transplantation, not only for cholangitis but also for the
      carcinoma when it is localized in the liver and the patient is carefully followed
      up.

PMID- 11455494
TI  - Advanced gallbladder carcinoma with biliobiliary fistula, resected by
      hepatopancreatoduodenectomy, in an aged patient.
AB  - We report a 78-year-old man with a gallbladder carcinoma and biliobiliary
      fistula, diagnosed by percutaneous transhepatic cholangioscopic biopsy through
      the fistula. The impacted stones in the common hepatic duct were crushed, and
      then selective cholangiography under percutaneous transhepatic cholangioscopy
      (PTCS) revealed a biliobiliary fistula. Cholangioscopic biopsy tissues taken from
      the gallbladder revealed adenocarcinoma, but biopsies taken from the fistula
      revealed no evidence of malignancy. Further investigations indicated that the
      gallbladder carcinoma involved the duodenum and the distal common bile duct. A
      hepatopancreatoduodenectomy, including both an extended right hepatic lobectomy
      with resection of the caudate lobe and a pancreatoduodenectomy, was performed.
      Despite the patient's advanced age, he made an unremarkable postoperative
      recovery and was able to enjoy an active social life for 8 months after the
      surgery. We discuss biliobiliary fistula associated with gallbladder carcinomas
      and the use of hepatopancreatoduodenectomy for advanced biliary cancer in aged
      patients.

PMID- 11455495
TI  - Clinical observation and treatment of leptospirosis.
AB  - The epidemiological and clinical observations of 240 patients with Weil's disease
      and 10 patients with canicola fever, and these observations in two epidemics of
      canicola fever, are presented. Early diagnosis is most important for the
      prognosis of patients with the severe form of leptospirosis. It depends on the
      clinical features, clinical laboratory findings, and the epidemiological
      situation. The most characteristic clinical signs for early diagnosis were
      febrile illness of sudden onset, severe general malaise, muscular pain, and
      conjunctival congestion. Proteinuria, leukocytosis with neutrophilia, and raised
      erythrocyte sedimentation rate were the most indicative clinical laboratory
      findings for early diagnosis. Although jaundice and hemorrhage are the most
      important signs of the severe form of leptospirosis, Weil's disease, these are
      rarely useful in early diagnosis. Of a variety of antibiotics used, penicillins
      and cephems had the lowest minimal inhibitory concentration against leptospires.
      However, it became apparent from basic studies in vitro and in vivo that
      streptomycin showed the best bactericidal action against leptospires and that it
      was the most effective anti-leptospiral antibiotic. Gentamicin, tobramycin, and
      isepamicin are also effective as alternatives to streptomycin. Although
      penicillins, cephems, tetracyclines, and macrolides are also effective for the
      treatment of leptospirosis, when these antibiotics with inadequate bactericidal
      activity are used for the treatment of the disease, long-term therapy with
      sufficiently large doses may be required from an early stage of the disease until
      the appearance of antibodies.

PMID- 11455496
TI  - Invasive streptococcal infections.

PMID- 11455497
TI  - The emergence of erythromycin-resistant Streptococcus pyogenes in Seoul, Korea.
AB  - High frequencies of erythromycin-resistant streptococci were reported in Japan in
      the mid-1970s, and in Finland in the late 1980s, related to an increase in the
      consumption of macrolide antibiotics in these countries. The frequency of
      erythromycin-resistant Streptococcus pyogenes was reported to be only 2% in 1994,
      but we know that the susceptibility of the strains to antibiotics had not been
      tested routinely. We studied the resistance rates of Streptococcus pyogenes to
      various antibiotics in Seoul, Korea, where antibiotics could be purchased without
      prescription. From January through December, 1998, 92 isolates of group A
      streptococci were collected from inpatients and outpatients with
      pharyngotonsillitis or invasive streptococcal infections, from institutions in
      five different geographic areas of Seoul; one pediatric clinic, three university
      hospitals, and one general hospital. All isolates were serotyped by T
      agglutination, and minimum inhibitory concentrations (MICs) were determined by
      agar dilution methods, according to the guidelines of the National Committee for
      Clinical Laboratory Standards (NCCLS). The most common T-serotype was T12
      (44.6%), followed by T4 (19.6%). All the isolates tested were susceptible to
      penicillin, vancomycin, and cefotaxime. However, 38 isolates (41.3%) were
      resistant to erythromycin, 32 (34.8%) were resistant to clindamycin, and 48
      (52.1%) were resistant to tetracycline. Twenty-seven of 41 isolates serotyped T12
      and 3 of 18 isolates serotyped T28 were multiresistant to erythromycin,
      clindamycin, and tetracycline. Almost half of the isolates obtained from the five
      different areas in Seoul showed erythromycin resistance in Streptococcus
      pyogenes. Routine monitoring of antibiotic susceptibility tests and further
      extensive nationwide surveys are needed to determine the frequency and the extent
      of the spread of resistant strains in various geographic regions in Korea.

PMID- 11455498
TI  - Artificial Pseudomonas aeruginosa biofilms and confocal laser scanning
      microscopic analysis.
AB  - Bacterial biofilms may be formed at various sites, including mucous membranes,
      teeth, and infectious lesions. To elucidate the structure and the function of
      biofilms, artificial biofilms of mucoid-type Pseudomonas aeruginosa organisms
      (strain PT1252) were made by centrifuging the organisms onto the surface of a
      coverglass and culturing further in broth media supplied continuously (45 ml/h).
      The biofilm structure at 4, 8, 12, and 24 h was visualized with fluorescent
      staining (SYTO9, propidium iodide [PI], and/or fluorescein isothiocyanate
      concanavalin A [FITC-ConA]) by confocal laser scanning microscopy (CLSM). It was
      clearly demonstrated that the number of bacteria (10(4)--10(6)/ml) could be
      estimated by their fluorescence intensity. Sectional analysis of each biofilm
      layer (1-microm thickness) made it possible to demonstrate the three-dimensional
      development of biofilms, and revealed that the biofilms were 9 microm in height
      after 12 h. The live and dead organisms were differentiated by SYTO9 and PI,
      respectively, in situ in biofilms, and about 13% of the organisms were dead in 12
      h-old biofilms. When 12-h-old biofilms were exposed to ciprofloxacin at minimum
      bactericidal concentration (6.26 microg/ml) for 90 min, all the organisms were
      killed, but some organisms (11 +/- 1.3%; n = 3) in 24-h-old biofilms with thicker
      and denser structure were still alive after exposure for 120 min. These results
      indicate that the CLSM analysis of artificial biofilms was useful for elucidating
      bacterial functions in biofilms, and may lead to a new quantitative system for
      estimating the bactericidal efficacy of antibacterial drugs in biofilms.

PMID- 11455499
TI  - Hospital outbreak of MEN-1-derived extended spectrum beta-lactamase-producing
      Klebsiella pneumoniae.
AB  - An outbreak of Klebsiella pneumoniae resistant to broad spectrum cephalosporins
      occurred in a hospital in the Kinki area in Japan. During 18 months, from
      February 1998 to July 1999, 23 strains were isolated from 21 patients (10 with
      pneumonia, 4 with urinary tract infection, 1 with sepsis, 1 with vaginosis, 1
      with a wound infection, and 1 with both pneumonia and sepsis; 3 patients showed
      noninfective colonization with K. pneumoniae) in seven wards, including the
      intensive care unit. MEN-1-derived gene was detected by polymerase chain reaction
      from the majority of the strains. Ninety-nine strains of K. pneumoniae were
      isolated during this period. The isolation rate of K. pneumoniae resistant to
      broad spectrum cephalosporins was 21%. We distinguished three clones by pulsed
      field gel electrophoresis and randomly amplified polymorphic DNA analysis, and
      one of them was isolated from 18 patients. The presence of an R-plasmid of more
      than 160 kb was confirmed by plasmid analysis, but it was not possible to obtain
      transconjugants from all strains. This outbreak of K. pneumoniae was immediately
      confirmed by genetic analysis, and it was promptly ended by the infection control
      procedures. This is the first hospital outbreak of MEN-1-producing K. pneumoniae
      in Japan.

PMID- 11455500
TI  - A study of quality assessment in clinical microbiology performance of independent
      laboratories in Tokyo: 18-year participation in the Tokyo Metropolitan Government
      External Quality Assessment Program.
AB  - We evaluated the performance of independent microbiology laboratories in Tokyo
      over an 18-year period of participation in the external quality assessment (EQA)
      program, and we estimated the impact of the EQA program. The study design was a
      longitudinal retrospective analysis of performance, including isolation,
      identification, and antimicrobial susceptibility testing of bacteria from
      simulated patients' samples, in "open" surveys compared with "blind" surveys.
      Independent microbiology laboratories, licensed by the Tokyo Metropolitan
      Government, have been subject to mandatory evaluation by the EQA program since
      1982. Survey reports, correspondence, annual guidance meetings, and inspections
      are used as quality improvement strategies. The performance for identification in
      "blind" surveys was significantly worse than that in "open" surveys (P < 0.001).
      Poorly performing laboratories had common features, including inadequate
      supervision by physicians and lack of familiarity with the impact of variations
      on the use of the standards. However, there were improvements in the performance
      of identification of some pathogens. The performance of susceptibility testing
      has not yet reached the relatively high level seen for identification. Some of
      the smaller laboratories have been gradually acquired by commercial chains
      operating outside Tokyo. The EQA program has established a role both in regard to
      laboratory improvement and as an educational tool. However, the program lags
      behind these of other developed countries in regard to the practical sciences.
      The main problems in regard to laboratory improvements are a shortage of human
      resources in clinical microbiology, lack of standardization of laboratory
      methods, and the pressures of financial constraints in the Japanese medical
      insurance system.

PMID- 11455501
TI  - Acute parvovirus B19 infection during anti-retroviral therapy.
AB  - Human parvovirus B19 (B19) has been described as a causative agent of chronic
      anemia in human immunodeficiency virus type-1 (HIV-1)-infected patients. We
      report an HIV-1 infected patient who had been receiving anti-retroviral therapy
      who showed sudden pancytopenia. Primary B19 infection was confirmed by the
      detection of plasma viremia and seroconversion. Although clearance required a
      prolonged period of time, the patient eventually cleared the B19 viral DNA from
      the plasma. More than likely, highly active anti-retroviral therapy (HAART),
      including a protease inhibitor, played a role in clearing the virus.

PMID- 11455502
TI  - The 7.5-kb common plasmid is unrelated to the drug susceptibility of Chlamydia
      trachomatis.
AB  - Using a new plaque cloning technique, we obtained unique Chlamydia trachomatis
      strains, which were confirmed to be free of the 7.5-kb common plasmid and
      glycogen in inclusions. The inclusions in plasmid-free and glycogen-negative
      strains were characterized by a target-like bull's eye morphology that appeared
      with the formation of a central translucent area that began to be seen clearly at
      30 h postinoculation. The clear zone was composed of gel materials originating
      from reticulate bodies (RBs) that were abnormally large in size and irregular in
      shape, although one could not differentiate the aberrant RBs from normal RBs at
      early stages of development. The in-vitro susceptibility of these strains to
      various chemotherapeutic antibiotics was tested by comparison with their parent
      strains possessing the common plasmid. No difference was detected for any of the
      antibiotics tested, indicating that the 7.5-kb common plasmid is unrelated to the
      drug susceptibility of C. trachomatis.

PMID- 11455503
TI  - Surveillance of bacterial resistance among isolates in Shanghai in 1999.
AB  - We report here surveillance data on the bacterial resistance of clinical isolates
      from 11 Shanghai hospitals in 1999, for guidance in the clinical use of
      antibacterial agents. Of the 14,855 strains collected, 5130 (34.5%) were Gram
      positive cocci and 9725 (65.5%) were Gram-negative bacilli. The most common
      organisms in descending order of frequency, were: Escherichia coli (16%),
      coagulase-negative staphylococci (CNS; 14.3%), Klebsiella spp. (12.3%),
      Staphylococcus aureus (11.5%), Pseudomonas aeruginosa (9.2%), Acinetobacter spp.
      (8.1%), and Enterococcus spp. (6.6%). Methicillin-resistant strains accounted for
      64% and 77% of S. aureus and CNS, respectively. The methicillin-sensitive strains
      were susceptible to most agents tested, while most methicillin-resistant strains
      were resistant to these agents. No vancomycin-resistant staphylococci were
      identified. Vancomycin-resistant strains accounted for 3.6% of Enterococcus
      fecalis and 1.7% of E. fecium. E. coli strains resistant to piperacillin,
      gentamicin, and fluoroquinolones accounted for 50% or more of the strains, and
      the resistance rates of Klebsiella spp., Enterobacter spp., Citrobacter spp., and
      Acinetobacter spp. to third-generation cephalosporins had increased markedly
      compared with rates in recent years. Resistance rates of P. aeruginosa to
      ceftazidime and imipenem (27% and 20%, respectively) had also increased compared
      with rates in recent years. A national strategy on the limited and prudent use of
      antibiotics is urgently needed.

PMID- 11455504
TI  - Comparison of in-vitro activities of SCH27899 and other antibiotics against
      Mycoplasma pneumoniae.
AB  - We examined the in-vitro activities of various antibiotics against 25 strains of
      Mycoplasma pneumoniae (22 clinical isolates and 3 standard strains). In the 22
      clinical isolates, the 90% minimum inhibitory concentrations (MIC 90) of
      SCH27899, ofloxacin, levofloxacin, ciprofloxacin, erythromycin, clarithromycin,
      roxithromycin, clindamycin, and minocycline were 16, 2, 2, 4, 0.0039, 0.0039,
      0.016, 2, and 4 microg/ml, respectively. The minimum bactericidal concentrations
      (MBC 90) of SCH27899, ofloxacin, levofloxacin, ciprofloxacin, erythromycin,
      clarithromycin, roxithromycin, clindamycin, and minocycline were 64, 4, 2, 8,
      0.0625, 0.0625, 0.125, 8, and 64 microg/ml, respectively. The low sensitivity of
      M. pneumoniae to SCH27899 may be a result of the impermeability of the bacteria
      to this molecule. The results of this study suggest that SCH27899 would not be a
      suitable antimicrobial agent to use in the alternative chemotherapy of M.
      pneumoniae infection.

PMID- 11455505
TI  - Hospital outbreak of MEN-1-derived extended spectrum beta-lactamase-producing
      Klebsiella pneumoniae.

PMID- 11455506
TI  - Surveillance of bacterial resistance among isolates in Shanghai in 1999.

PMID- 11455507
TI  - Appearance of right bundle branch block in electrocardiograms of patients with
      pulmonary embolism as a marker for obstruction of the main pulmonary trunk.
AB  - A number of changes occur in the electrocardiogram (ECG) of pulmonary embolism.
      This article deals with the diagnostic value of the newly emerged right bundle
      branch block (RBBB) as a manifestation of acute right ventricular overload. A
      certain correlation between the extent of obstruction of the pulmonary artery and
      the appearance of RBBB is established through dynamic monitoring of the ECG.
      Fifty cases of dissectionally proven pulmonary embolism are observed, in 20 of
      which massive trunk obstruction had taken place, and in the remaining 30
      peripheral embolism in the pulmonary artery was established. With 80% of the
      trunk embolism patients (16 cases), a newly emerged RBBB was detected in their
      ECG, and with the remaining 20% (4 cases), ST-segment depression and T-wave
      inversion in leads V(1)-V(4) were observed as well as right axis deviation.
      S(1)Q(3)T(3) syndrome was detected among 60% (12 cases) of trunk embolism
      patients. In none of the peripheral embolism cases was RBBB in the ECG
      registered. Thus, its appearance on dynamic monitoring of the ECG of pulmonary
      embolism patients is a significant sign of the probability of massive obstruction
      of the main pulmonary trunk.

PMID- 11455508
TI  - Signal-averaged P-wave ECG discriminates between persistent and paroxysmal atrial
      fibrillation.
AB  - Atrial fibrillation (Afib) has been associated with abnormal signal-averaged P
      wave (SAPW) parameters but whether SAPW is associated with the time course of
      these arrhythmias (persistent vs. paroxysmal, frequent vs. rare episodes) remains
      unknown. This article assesses the significance of SAPW duration in
      distinguishing patients with paroxysmal from those with persistent Afib. SAPW
      electrocardiogram was performed with a "double triggering" software system for
      acquisition and analysis of data. SAPW total duration (TD), X, Y, and Z leads
      magnitudes and vector signal magnitudes were measured offline. Optimal cutoff
      value between control and patient groups was determined by using a receiver
      operator characteristic curve. Data were analyzed to compare controls with
      patients groups and between patient groups according to time course of the
      arrhythmic history. Fifteen age-matched patients without a history of Afib and 55
      patients with a history of Afib (33 with paroxysmal and 22 with persistent
      arrhythmia) were studied off antiarrhythmic drugs. Patients with history of
      persistent arrhythmia were studied within 2 days after electrical cardioversion
      to sinus rhythm. SAPW TD was the only parameter consistently associated with
      Afib. SAPW TD was 98 +/- 6 ms (mean +/- SD) in the control group, 127 +/- 19 ms
      in the pooled patients group (P =.0001); 122 +/- 20 ms for paroxysmal and 133 +/-
      17 ms for the persistent Afib group (P =.04). Analysis of other SAPW parameters
      were not statistically significant. SAPW duration is a simple method to identify
      patients with history of Afib. A significantly longer SAPW TD characterizes
      patients with a history of persistent as opposed to paroxysmal Afib. Prolongation
      of SAPW TD possibly reflects more advanced electrophysiological changes, creating
      a more stable substrate that leads to persistence of the arrhythmia.

PMID- 11455509
TI  - QRS axis in isolated perimembranous ventricular septal defect and influences of
      morphological factors on QRS axis.
AB  - To detect the frequency of left axis deviation (LAD) in isolated perimembranous
      ventricular septal defects (VSD) we retrospectively analyzed electrocardiograms
      of 59 patients, aged 8 months to 15 years. Patients were grouped into those
      having ventricular septal aneurysm (VSA) formation (n:20) and those who did not
      have VSA (n:39). Patients with VSA were then stratified into 2 groups according
      to the presence of left ventricular-to-right atrial (LV-RA) shunt. Four hundred
      healthy children served as the control group. We found that 12 (20.3%) of 59
      patients with isolated perimembranous VSD had a LAD. Five of 6 patients with
      perimembranous outlet VSD and 6 with perimembranous inlet VSD had abnormal LAD
      with a qR pattern in I and aVL and rS in aVF. Abnormal LAD was more prevalent in
      patients with VSA (40%) than without VSA (7.7%) (P <.01). We also found that mild
      right ventricular hypertrophy (RVH) with the rsR' or rSR' pattern in V1 was more
      frequent in patients with VSA, especially those who had LV-RA shunt. However, we
      could not find significant difference between patients with or without LV-RA
      shunt for the incidence of abnormal LAD and mild RVH. Localization of
      perimembranous VSD was not found to have an effect on frequency of abnormal LAD
      and mild RVH in this patient group. In patients with clinical findings of VSD,
      the existence of abnormal LAD especially if it is associated with mild RVH,
      should raise the possibility of perimembranous VSD with VSA formation.

PMID- 11455510
TI  - QRS axis in isolated perimembranous ventricular septal defect.

PMID- 11455511
TI  - Absent septal Q waves in otherwise normal electrocardiograms--a variant of
      normal?
AB  - Absence of septal Q waves can be defined as the simultaneous absence of Q waves
      from all of leads I, V(5), and V(6). This has been considered abnormal by some
      investigators, but whether this is true of tracings lacking other abnormalities
      is uncertain. In electrocardiograms (ECGs) from 4,174 patients, 95 were found
      that were normal except for absence of septal Q waves. Clinical characteristics
      of these were compared to those of age- and gender-matched patients having normal
      ECGs with septal Q waves. The ratio of the number of patients with normal ECGs
      except for absent septal Q waves to the number of patients with entirely normal
      ECGs was independent of age. Most patients having normal ECGs except for absent
      septal Q waves had clinically normal hearts, and they were not significantly more
      likely to have apparent cardiovascular disease than age- and gender-matched
      controls with septal Q waves. It is concluded that absence of septal Q waves in
      otherwise normal ECGs may be a variant of normal.

PMID- 11455512
TI  - The cumulative effects of historical and physical examination findings on the
      prognostic value of the electrocardiogram.
AB  - The electrocardiogram has been shown in epidemiologic studies to be an
      independent predictor of survival. These studies have adjusted for selected
      covariates simultaneously. This article assesses the value of the
      electrocardiogram as a predictor of survival when introduced at progressive
      stages of the common clinical encounter. Data collected from 4,518 patients ages
      of 60 to 96 years with isolated systolic hypertension who were followed-up for up
      to 6 years as part of the Systolic Hypertension in the Elderly Project were
      analyzed. Survival curves and 3- and 5-year survival rates (Cox regression
      methods) of groups with normal and abnormal resting electrocardiograms were
      compared. Blocks of covariates representing demographic information, risk factors
      for cardiovascular disease, clinical history, and physical examination findings
      were added to the survival models sequentially to mimic the sequence of the
      common clinical encounter, and the independent significance of the
      electrocardiogram as a predictor of survival was assessed at each step. An
      abnormal electrocardiogram was associated with reduced survival when no
      adjustment for covariates is made. Survival was also significantly (P <.05)
      different for groups with normal and abnormal electrocardiograms when demographic
      and risk factor variables were included in the statistical models, but not after
      findings from the clinical history and physical examination were added. The
      prognostic value of the electrocardiogram varies with the stage in the clinical
      encounter in which it is introduced.

PMID- 11455513
TI  - Variability in repeated pattern ventricular arrhythmia: application of a reentry
      model.
AB  - Repeated pattern ventricular arrhythmia (RPVA) is often observed in
      electrocardiogram recordings as a repeated sequence of a fixed number of normal
      sinus QRS complexes interposed between ventricular ectopic beats. The number of
      interposed sinus complexes is defined as the order of the repeated pattern
      ventricular arrhythmia. Regions of orders as a function of sinus RR and coupling
      intervals and duration of refractory periods of normal conduction and reentry
      pathways were derived from a computer model that simulates a reentry mechanism.
      Refractory periods of both the normal and reentry conduction pathways could be
      estimated from electrocardiogram measured time intervals. A variable relationship
      of RR intervals for different orders was found among patients. According to the
      reentry model, these order changes were more likely to occur with changes in the
      reentry refractory period than with heart rate changes. The longer RR intervals
      of interpolated beats in some patients were also explained by the model.

PMID- 11455514
TI  - The 12-lead electrocardiogram in anorexia nervosa: A report of 2 cases followed
      by a retrospective study.
AB  - Anorexia nervosa (AN) has been associated with various cardiac disorders and
      several electrocardiographic abnormalities, the most prominent being sudden death
      and prolonged QT duration and dispersion. We report 2 cases of AN with marked
      repolarization abnormalities, the first clearly related to electrolyte imbalance,
      the second without a good explanation from metabolic, electrolytic or
      pharmacological sources. A retrospective analysis of 47 other consecutive
      patients with AN showed that sinus bradycardia was the most common ECG finding,
      but that QT or QTc interval prolongation was not a typical feature, being present
      in only 1 patient. The sole variable slightly correlated with QTc duration was
      the serum potassium concentration. Consequently, marked repolarization changes
      (QT interval and/or T wave morphology) in AN should not be taken as a feature of
      the disease, but should call for the search of potential causes such as metabolic
      and electrolytic disturbances, drug effects, or a possible genetic component.

PMID- 11455515
TI  - Investigation on diabetic autonomic neuropathy assessed by power spectral
      analysis of heart rate variability in WBN/Kob rats.
AB  - This article investigates the development of cardiovascular autonomic dysfunction
      caused by diabetes mellitus. We performed power spectral analysis of heart rate
      variability in WBN/Kob rats as a model of spontaneous diabetes. The heart rate of
      the rats was measured continuously for 24 hours with an implanted telemetric
      transmitter, and power spectral analysis of heart rate variability was performed
      on continuous electrocardiograms. At 4 to 5 months of age, the rats indicated a
      tendency toward a decrease in plasma insulin concentration without hyperglycemia.
      At 8 to 9 months of age, they showed remarkable hyperglycemia, loss of the
      circadian rhythm of the heart rate, and reversion or loss of the circadian rhythm
      of the blood pressure. By the power spectral analysis of heart rate variability,
      it became apparent that the circadian rhythm of the low frequency/high frequency
      ratio was absent even in prediabetic WBN/Kob rats. In addition, the circadian
      rhythms of the high-frequency power level and low frequency/high frequency ratio
      were absent in diabetic WBN/Kob rats. These findings indicate that the autonomic
      nervous system in WBN/Kob rats is progressively damaged from the prediabetic to
      diabetic state. In conclusion, diabetic autonomic neuropathy may be characterized
      by the appearance of sympathetic overactivity that precedes the impairment of
      parasympathetic activity.

PMID- 11455516
TI  - Ventricular parasystolic couplets originating in the pathway between the
      ventricle and the parasystolic pacemaker: mechanism of "irregular" parasystole.
AB  - This article explains the mechanism of "irregular" parasystole. Two theories have
      been suggested: "electrotonic modulation" and "type I second degree entrance
      block." This study attempts to clarify the mechanism of irregular parasystole in
      cases of true ventricular parasystole associated with ventricular parasystolic
      couplets. Cases associated with ventricular parasystolic couplets were selected
      from 37 clinical cases of true ventricular parasystole in which one or more pure
      parasystolic cycles with no intervening nonectopic QRS complexes were found. Of
      the 37 cases of true ventricular parasystole, ventricular parasystolic couplets
      were found in 4 cases. In none of the other 33 cases, ventricular parasystolic
      couplets were found. In all the cases coexisting with ventricular parasystolic
      couplets, the latter ectopic QRS complex of the couplet failed to reset the
      parasystolic rhythm. The above findings suggest that the latter ectopic QRS
      complex of the parasystolic couplet originated not in the parasystolic pacemaker
      but in the pathway between the ventricle and the parasystolic pacemaker. It seems
      that when a sinus impulse fell late in the parasystolic cycle, it passed through
      the site of second degree entrance block and that the parasystolic couplets
      originated from the reentrant pathway between the ventricle and the pacemaker.
      This strengthens our previous suggestion that the mechanism of irregular
      parasystole is governed by "type I second degree entrance block" and not by
      "electrotonic modulation."

PMID- 11455517
TI  - Clinical consequences of ST-segment changes caused by body position mimicking
      transient myocardial ischemia: hazards of ST-segment monitoring?
AB  - A case is described in which an acute ST-segment change, presumably due to a
      change in body position, is erroneously interpreted as an acute ischemic event.
      Positional ST-segment changes during continuous, multi-lead electrocardiographic
      (ECG) monitoring are particularly challenging to distinguish from transient
      myocardial ischemia because 1) positional ECG templates are often not feasible to
      record at the beginning of monitoring in unstable patients; 2) positional ECG
      templates, if recorded, are often not readily accessible to clinicians for later
      comparison; 3) body position cannot be correlated with ST events because patients
      are out of the direct view of nurses during the event or clinicians review ST
      trends at a later time; 4) ST monitors typically do not store ECGs frequently
      enough to be able to observe on the ST trend the gradual ("ramp-like") onset of
      ST changes that is characteristic of transient ischemia; and 5) absence of chest
      pain with a ST event does not help clinicians identify false alarms because it is
      well understood that the majority of ischemic events are clinically silent.

PMID- 11455518
TI  - Unusual ECG responses to exercise stress testing.
AB  - We describe the case of a patient with coronary artery disease who developed
      transient ST-segment depression, right bundle branch block (RBBB), left anterior
      hemiblock, ST-segment elevation +ST), and "giant" T-waves in her
      electrocardiogram (ECG), an assortment of ECG patterns heretofore unreported in
      conjunction with exercise stress testing (EST). The amplitude of the +ST was
      modulated by the superimposed RBBB, as was shown by its augmentation after the
      abrupt disappearance of RBBB. Following recession of the latter "giant" T-waves,
      which usually are encountered in the hyperacute phase of myocardial infarction,
      developed and persisted late in the recovery period. Cardiac enzymes after EST
      were negative, and arteriography revealed a stenotic left anterior descending
      coronary artery. The present case indicates that a variety of ECG expressions of
      severe transmural ischemia or myocardial infarction can also be manifest in the
      course of EST; this also suggests a common pathophysiological mechanism in severe
      EST-triggered ischemia and the early phase of myocardial infarction.

PMID- 11455519
TI  - Electrophysiological characteristic of a patient exhibiting the short-coupled
      variant of torsade de pointes.
AB  - A 41-year-old man was admitted because of syncope. The electrocardiogram showed
      torsade de pointes (Tdp) with no long QT interval and the coupling interval of
      the initial beat of Tdp was 240 ms. Heterogeneity of ventricular refractoriness
      was observed together with shortness of the effective refractory period measured
      at the right ventricular inflow site where the paced QRS morphology was the same
      as that of the initial beat of Tdp. Verapamil could suppress frequent ventricular
      premature complexes with a short coupling interval, which lead to Tdp.
      Polymorphic ventricular tachycardia was induced by triple ventricular
      extrastimuli. A pure potassium channel blocker was successful in inhibiting
      polymorphic ventricular tachycardia inducibility by prolongation of
      refractoriness. These results suggested that triggered ventricular premature
      complexes may be represent the initiating mechanism, whereas the shortness of
      local refractory period and heterogeneity of ventricular refractoriness may play
      a role in the development and the maintenance of the Tdp.

PMID- 11455520
TI  - Urban renal disease: reflections of an urban nephrologist.
AB  - On completion of a Nephrology fellowship, I went back to the inner city community
      where I was raised to begin my practice. Filled with idealism, I believed that,
      by returning, I could slow the devastation that hypertension was imparting on the
      black community, and in doing so, prevent end-stage renal disease (ESRD). It was
      soon obvious that this view was naive. Although the government is willing to
      spend $60,000 per dialysis patient per year, there is no adequate system for, nor
      funding of, prevention. Social factors impact on prevention as well. Black
      physicians are often not readily accepted on staffs of hospitals in their own
      communities. The community itself often values medical care more highly from
      others not of their own race. Medical schools, located in inner city
      neighborhoods, rarely encourage their graduates to practice in the local
      communities. Economic issues result in varying access to care, with the poorest,
      who often have the highest needs, receiving the least. Effective change will
      occur only when there is a concerted multidisciplinary approach, led by respected
      leaders in the black community (nurses, physicians, preachers, social workers,
      teachers, and politicians) to create an atmosphere of empowerment within the
      community residents.

PMID- 11455521
TI  - Renal disease in the inner city.
AB  - For various ethnic and socioeconomic reasons the pattern of renal disease in the
      inner city displays distinctive features. Hypertension is frequent, often
      intractable, and generally conditioned by salt sensitivity and a high sodium
      intake. Chronic hypertensive nephrosclerosis, found predominantly in African
      Americans, comprises marked cardiomegaly, renal shrinkage, and hypertensive
      retinopathy. It has been overdiagnosed in the past, but actually accounts for
      less than 20% of end-stage renal disease (ESRD) in African Americans. Malignant
      hypertension, less frequent nowadays, may cause renal shutdown, which is
      reversible in a few cases; the heart and kidneys are often of normal size.
      Idiopathic focal segmental glomerulosclerosis is the most common cause of the
      primary nephrotic syndrome in blacks, but its incidence has also been rising in
      whites and Hispanics; it does not respond well to treatment, and almost one half
      of the patients develop ESRD within 10 years. Systemic lupus erythematosus is
      also more common in African Americans, in whom the severe proliferative forms of
      lupus nephritis pursue a more virulent course: one half of such patients develop
      ESRD in 5 years. Cocaine, the use of which has assumed epidemic proportions, may
      cause accelerated hypertension, acute renal failure from rhabdomyolysis, and
      progression of preexisting renal disease. Heroin nephropathy has all but
      disappeared and has been replaced by human immunodeficiency virus (HIV)
      nephropathy. The prognosis of HIV-infected patients maintained by dialysis has
      greatly improved. Sickle glomerulopathy, consisting of mesangial expansion,
      basement membrane duplication, and the absence of immune deposits, may cause the
      nephrotic syndrome in 4% of patients with severe sickle cell anemia, heralding
      death within 2 years in one half of patients and ESRD in two thirds; survival has
      not improved with dialysis. Diabetes is now the most common cause of ESRD.
      Familial aggregation of ESRD is frequently encountered. Interventions useful in
      the general population, such as vascular bypass procedures, should be undertaken
      with great caution and restraint in dialysis patients.

PMID- 11455522
TI  - Practice pattern and treatment options for kidney patients in a single North
      Italian nephrology center.
AB  - The experience and the current practice of a single center located in northern
      Italy is reported. The center of Vicenza is a self-standing nephrologic unit
      serving a population of about 300,000 individuals. The overall province counts
      approximately 800,000 individuals and some of them are referred to our center
      from peripheral hospitals for renal transplantation and/or particular pathologic
      conditions. The center offers an integrated approach to the treatment of uremia
      including hemodialysis (HD), peritoneal dialysis (PD), and renal transplantation.
      In HD and PD, the most peculiar aspect is the treatment personalization that
      leads to numerous types of applied therapies and technologies. The policy of the
      center is based on the belief that the nephrology team has a substantial
      influence on the outcomes of dialysis patients. A large number of treatment
      options are available. Special care is placed on the delivery of an adequate
      amount of dialysis, but the fractional clearance of urea in relation to volume
      (Kt/V) is seen as a prerequisite and other factors are considered important.
      Reduction in mortality and morbidity is largely dependent on beginning therapy
      early in the course of renal treatment. The attainment of appropriate hemoglobin
      concentrations, good nutrition, good control of calcium and phosphorus
      metabolism, lipids, and blood pressure, is considered of great importance. Beyond
      all these factors the time spent by the physician with the patient is considered
      one of the major factors influencing quality of care. The particularly low
      mortality of the center (6%/yr) may also be ascribed to a lower incidence of
      diabetes and other comorbidities.

PMID- 11455523
TI  - The outcome of the urban renal patient: the importance of social factors and
      center effects.
AB  - Caring for the urban renal patient can be a challenge to providers for many
      reasons. Although racial and socioeconomic factors have an impact on the health
      of this population, one must also consider the effect of the urban environment on
      the ill, especially those with renal disease. This article reviews the state of
      health among the poor and nonwhite minorities, who tend to inhabit the urban
      regions of this country, and then highlights the unique characteristics of those
      with renal disease. The impact of the Medicare end-stage renal disease (ESRD)
      program and center-specific quality of care on the outcome of the urban patient
      with ESRD is explored.

PMID- 11455524
TI  - Cocaine use and chronic renal failure.
AB  - Urban communities vary from suburban and rural communities in several ways, which
      are reflected in a modified risk for different causes of chronic renal disease.
      Many rural communities are more similar to urban communities in regard to
      socioeconomic adversities, access to health care, and other related challenges.
      It is important to recognize that high population density is commonly associated
      with a unique set of cultural practices including higher rates of perceived
      stress, recidivism and incarceration, and substance abuse. Each of these may
      predispose to higher rates of selected renal disorders such as hypertensive
      nephrosclerosis, human immunodeficiency virus (HIV) nephropathy, and substance
      abuse-associated renal disease. Having an understanding of urban culture and
      lifestyle can increase the awareness of potential contributing factors to chronic
      renal failure (CRF) in this population and assist in developing screening
      programs for high-risk individuals, considering specific diagnoses that may not
      be readily apparent and implementing effective early treatment.

PMID- 11455525
TI  - Factors influencing access to cardiovascular procedures in patients with chronic
      kidney disease: race, sex, and insurance.
AB  - Blacks and women are less likely to undergo invasive cardiac procedures than
      whites and men in patients with chronic renal disease. We determined the
      relationship between ethnic and sex differences in access to cardiac procedures
      as patients progress to ESRD and acquire Medicare insurance. We performed a
      cohort study of a nationwide random sample of 4,987 patients who progressed to
      ESRD in 1986 to 1987 and were followed up for 7 years was used. Data were
      collected from medical charts and Medicare administrative records. Pre-ESRD, the
      odds of cardiac procedure use were much lower for white women (adjusted odds 0.67
      [95% confidence interval (CI) 0.49-0.92]), black men (adjusted odds 0.32 [95% CI
      0.20-0.49]), and black women (adjusted odds 0.30 [95%CI 0.18-0.50]) compared with
      white men. After initiating dialysis therapy, the ethnic and sex differences
      decreased with odds of receiving a cardiac procedure compared with white men 0.88
      (95% CI 0.63-1.21) for white women, 0.66 (95% CI 0.47-0.92) for black men, and
      0.75 (95% CI 0.53-1.08) for black women. Patients uninsured pre-ESRD had the
      largest increase in procedure rates at follow-up. The wide pre-ESRD disparities
      in cardiac procedure use between white women, black men, and black women compared
      with white men narrowed substantially with acquisition of Medicare and entry into
      comprehensive dialysis care. Health insurance contributed to the narrowing of
      differences. Procedure use for black men still lagged behind the other groups,
      suggesting the need for closer examination of health needs in this potentially
      vulnerable group.

PMID- 11455526
TI  - Income-based disparities in outcomes for patients with chronic kidney disease.
AB  - The impact of income on outcomes for patients with end-stage renal disease
      (ESRD), who are largely relieved of structural and financial barriers to care, is
      poorly understood. We conducted a prospective cohort study of 3,165 patients who
      developed ESRD in the early 1990s to examine whether low-income patients with
      ESRD have poorer health outcomes than their socioeconomically advantaged
      counterparts, and, if so, to determine whether greater health insurance can
      reduce this disparity. We found that increasing neighborhood income was
      associated with decreased mortality and an increased likelihood of placement on
      the renal transplant waiting list. The presence of private insurance coverage in
      addition to Medicare improved rates of listing for transplantation in a graded
      manner, with the greatest effect among those living in neighborhoods below the
      10th percentile of income, but had no effect on socioeconomic disparities in
      mortality. Our results suggest that low-income patients with ESRD experience
      persistent financial barriers to transplantation that can be addressed with
      greater health benefits. However, they also experience higher mortality that is
      caused by personal and/or environmental factors that differ by social class.
      Clinicians, researchers, and policymakers must address these social, cultural,
      psychologic, and environmental determinants of health to improve the survival of
      patients with ESRD.

PMID- 11455527
TI  - Hypertension and medication-related renal dysfunction in the HIV-infected
      patient.
AB  - Given the improved life expectancy with highly active antiretroviral therapy
      among patients with human immunodeficiency virus (HIV)-infection, the treatment
      of medical problems such as hypertension will become increasingly more important.
      Although HIV-infected patients are at increased risk for the development of
      pulmonary hypertension, there is little data to suggest they are at increased
      risk for systemic hypertension or secondary causes of hypertension. Multiple
      potential drug interactions exist between antiretroviral medications,
      particularly the protease inhibitors and antihypertensive medications.
      Additionally, certain antiretroviral medications have frequent and important side
      effects relating to the kidneys and urinary system. Knowledge of these
      interactions and side effects is essential toward caring for the patient with HIV
      infection.

PMID- 11455528
TI  - HIV-associated nephropathy: an urban epidemic.
AB  - Human immunodeficiency virus-associated nephropathy (HIVAN) is the most common
      form of chronic renal disease in HIV-1-seropositive patients. Over 85% of cases
      of HIVAN occur in African-American patients and it is the third leading cause of
      ESRD in blacks age 20 to 64. Changes in incidence rates of HIVAN have coincided
      with changes in AIDS incidence rates. The demographics of the AIDS/HIV-1 epidemic
      indicate that the risk pool for HIVAN will continue to grow and that urban
      Nephrology centers will continue to see high rates of HIVAN. In addition,
      improvements in survival rates of HIV-1-seropositive patients on hemodialysis and
      improved treatment of HIVAN with highly active antiretroviral therapy (HAART) and
      angiotensin-converting enzyme (ACE)-inhibitors will result in an increased
      prevalence of HIVAN in the end-stage renal disease (ESRD) and pre-ESRD patient
      populations.

PMID- 11455529
TI  - Racial and socioeconomic factors in glomerular disease.
AB  - The influence of racial and socioeconomic factors on the incidence, prognosis,
      and response to therapy of many diseases has long been noted. Although glomerular
      diseases comprise 10% to over 16% of the dialysis and renal transplant
      populations, respectively, only recently have racial and socioeconomic factors
      been evaluated. Several glomerular diseases are associated with a striking
      African-American predominance. These include idiopathic focal sclerosis, and
      especially its collapsing variant, human immunodeficiency virus (HIV)-associated
      nephropathy, and severe lupus nephritis. In many of these entities the renal
      disease is also more aggressive and rapidly progressive than in other
      populations. Recent data points to genetic-biologic as well as social and
      economic factors that may be responsible for these findings. Studies dealing with
      the therapy of glomerular lesions must be stratified for racial and social
      background differences to avoid bias in outcome. Whether racial and socioeconomic
      data should be used in treating individual patients, and how, remains an area of
      controversy.

PMID- 11455530
TI  - Funding ESRD care through charity: the paradigm of the National Kidney Foundation
      of Singapore.
AB  - Given the prohibitive costs of end-stage renal disease (ESRD) care for certain
      countries and the increasing incidence of ESRD worldwide, alternative methods of
      funding dialysis care are increasingly necessary. We describe the paradigm of the
      National Kidney Foundation of Singapore (NKF-S), the provider of subsidized
      dialysis care and comprehensive rehabilitative services to approximately 60% of
      all ESRD patients in the country, whose activities are funded entirely by
      charitable public donations. Unique to the NKF-S model are the considerations of
      the donor as an "investor" in the health care of NKF-S dialysis patients, the
      personal responsibility of the dialysis patient as a recipient of this
      "investment" to play an active role in achieving good clinical and rehabilitative
      outcomes, and the fostering of community-based support systems to facilitate
      patient rehabilitation such as partnerships with employers willing to employ
      dialysis patients. The success of the system is shown by its clinical outcomes,
      which approximate those observed in the United States. We believe that several
      aspects of the NKF-S model for ESRD care may be implemented in other communities,
      particularly in countries that have yet to develop financially and clinically
      mature dialysis programs.

PMID- 11455531
TI  - An assessment of the effectiveness of the Mottep model for increasing donation
      rates and preventing the need for transplantation--adult findings: program years
      1998 and 1999.
AB  - The National Minority Organ Tissue Transplant Education Program (MOTTEP)
      evaluated the effects of a community-implemented health education program for
      adult members of minority population groups to affect attitude, knowledge, and
      intent to change behavior. In addition, this study represents 1 of the first
      major initiatives to formally address prevention as a strategy to contribute to
      reducing the need for organ/tissue transplantation among minorities in the United
      States. The study targeted students (youth) and adults representing different
      ethnic groups (African-Americans, Alaskan Natives, Filipinos, Latinos, and Native
      Americans) who attended health education presentations addressing organ tissue
      donation, transplantation, and illness prevention in 15 different cities in
      churches, schools, and other sites. A cross-sectional study that used
      questionnaires was designed for collecting data from all participants. This
      article presents data on the adult sample only. Preintervention and
      postintervention data were collected from 914 adult participants to determine any
      immediate effects of the intervention. By using data from matched sets of the
      preintervention and postintervention questionnaires for all adult participants,
      there were significant increases in (P < or =.000) trust in doctors, future plans
      to become organ donors, and in participants' spiritual/religious beliefs about
      organ/tissue donation. There was also a significant increase (P <.05) in
      participants' awareness of the perceived need for organ/tissue donation. African
      American participants were significantly more likely (P < or =.000) to report
      trust in doctors, future plans to donate organs/tissue, and perceive the need for
      donation as a result of MOTTEP presentation. Caucasian participants showed a
      significant increase (P < or =.007) in trust in doctors, perceived need for organ
      donation (P < or =.05), and in shifting spiritual/religious beliefs about
      organ/tissue donation (P < or =.02). Attitudes, knowledge, beliefs, and
      behavioral intentions about organ/tissue donation and illness prevention can be
      affected by culturally appropriate health education programs designed for
      targeted population groups. Sustained changes in behavioral intentions toward
      organ donation and illness prevention may require multiple educational
      interventions in different community settings to increase donation rates and
      improve behavioral health practices to prevent illness.

PMID- 11455532
TI  - An ultrastructural study of germ cells during ovarian differentiation in Torpedo
      marmorata.
AB  - An ultrastructural investigation, performed on embryos, neonates, subadult and
      adult females, demonstrated that in Torpedo marmorata oogenesis occurs very early
      in life and continues, in its proliferative phase, also after birth. Clusters of
      early meiotic cells were already evident in the ovarian cortex of 6-cm-long
      embryos, as well as in the ovary of newborns and three-month-old young.
      Conversely, in the ovaries of subadult and adult females, all the germ cells
      present were organized into follicles, and no clusters of oogonia and early
      meiotic cells were generally found in the cortex, except for one adult female
      where clusters of germ cells not organized in follicles were found in the cortex.
      These data demonstrated that, in Torpedo marmorata, oogenesis is immediate, and,
      as oogonia persist after birth, more similar to that of mouse, monkey, rabbit,
      and ferret (Mauleon Arch Anat Microsc, 1967; 56:125-150; Byskov and Hoyer 1994)
      than to that of human, rat, pig, and guinea pig (Byskov and Hoyer 1994). Such a
      pattern is in agreement with the reproductive strategy of Torpedo, a scantly
      prolific species with low uterine fecundity. The presence of meiotic cells that
      are not organized in follicles in one adult female might be consistent with the
      large individual variability characterizing cartilaginous fishes. The possibility
      that such a character is typical of mature females should be rejected as oogonia
      and early meiotic cells were not found inside the totally sectioned gonads of
      subadult and adult females.

PMID- 11455533
TI  - Relationship between postsynaptic NK(1) receptor distribution and nerve terminals
      innervating myenteric neurons in the guinea-pig ileum.
AB  - The amounts of neurokinin 1 (NK(1)) receptor immunolabelling on the membranes of
      myenteric cell bodies at appositions with tachykinin-immunoreactive nerve
      terminals, other nerve terminals, and glial cells were compared at the
      ultrastructural level using pre-embedding, double-label immunocytochemistry.
      NK(1) receptor immunoreactivity was revealed using silver-intensified, 1 nm gold,
      and tachykinin-immunoreactive nerve terminals were revealed using
      diaminobenzidine. The density of NK(1) receptor immunolabelling (silver particles
      per length of cell membrane) on the membrane at appositions with tachykinin
      immunoreactive nerve terminals was not significantly different from that at
      appositions with other (nonimmunoreactive) nerve terminals or with glial cells.
      Synaptic specializations ("active zones") were present at a small proportion of
      the appositions between NK(1) receptor-immunoreactive cell bodies and tachykinin
      immunoreactive or other nerve terminals. The density of NK(1) receptor
      immunolabelling at synaptic specializations was lower than that at regions of
      appositions where no synaptic specializations were present. The presence of NK(1)
      receptor on the cell surface in areas not directly apposed to tachykinin
      containing nerve terminals suggests that tachykinins that diffuse away from their
      site of release may still exert an action via NK(1) receptors. Although NK(1)
      receptors do not appear to be targetted to particular sites on the surfaces of
      myenteric nerve cell bodies and proximal dendrites, they are reduced in density
      at regions of the membrane-forming synaptic specializations.

PMID- 11455534
TI  - Stereological determination of the volume of the rat hemimandible tissues.
AB  - Rodent incisors are useful models to study the development and behavior of dental
      and periodontal tissues. Some studies require three-dimensional reconstructions
      of the tooth but none of the described methods yield actual volumetric data.
      Unlike the rat lower incisors the hemimandible can be easily isolated and its
      volume was determined by Cavalieri's geometrical principle. This method
      associated with point-counting volumetry was used to calculate the volume of the
      structures found in that bone mainly those related to the lower incisor. For 172
      g male rats the mean volume of the hemimandible was 182.7 mm(3), statistically
      not different from 184.9 mm(3) the mean volume of the same hemimandibles
      determined by Archimedes' principle. The coefficients of error (CE) of
      Cavalieri's estimates for the hemimandible, incisor as a whole (the tooth itself,
      odontogenic region and periodontium) and bone tissue were less than 0.04. For the
      incisor individual tissues the CEs were usually above 0.05, however their
      calculated volumes are probably not different from the actual ones. The data for
      incisors and their periodontal tissues and for bone, because of continuous growth
      of these structures, are meaningful only for rats of the same gender, strain and
      weight range.

PMID- 11455535
TI  - Development and maturation of taste buds of the palatal epithelium of the rat:
      histological and immunohistochemical study.
AB  - Palatal taste buds are intriguing partners in the mediation of taste behavior and
      their spatial distribution is functionally important for suckling behavior,
      especially in the neonatal life. Their prenatal development has not been
      previously elucidated in the rat, and the onset of their maturation remains
      rather controversial. We delineated the development and frequency distribution of
      the taste buds as well as the immunohistochemical expression of alpha-gustducin,
      a G protein closely related to the transduction of taste stimuli, in the
      nasoincisor papilla (NIP) and soft palate (SP) from the embryonic day 17 (E17)
      till the postnatal day 70 (PN70). The main findings in the present study were the
      development of a substantial number of taste pores in the SP of fetal rats (60.3
      +/- 1.7 out of 122.8 +/- 5.5; mean +/- SD/animal at E19) and NIP of neonatal rats
      (9.8 +/- 1.0 out of 44.8 +/- 2.2 at PN4). alpha-gustducin-like immunoreactivity (
      LI) was not expressed in the pored taste buds of either prenatal or newborn rats.
      The earliest expression of alpha-gustducin-LI was demonstrated at PN1 in the SP
      (1.5 +/- 0.5 cells/taste bud; mean +/- SD) and at PN4 in the NIP (1.4 +/- 0.5).
      By age the total counts of pored taste buds continuously increased and their
      morphological features became quite discernible. They became pear in shape,
      characterized by distinct pores, long subporal space, and longitudinally oriented
      cells. Around the second week, a remarkable transient decrease in the total
      number of taste buds was recorded in the oral epithelium of NIP and SP, which
      might be correlated with the changes of ingestive behaviors. The total counts of
      cells showing alpha-gustducin-LI per taste bud gradually increased till the end
      of our investigation (14.1 +/- 2.7 in NIP and 12.4 +/- 2.5 in SP at PN70). We
      conclude that substantial development of taste buds began prenatally in the SP,
      whereas most developed entirely postnatal in the NIP. The present study provides
      evidence that the existence of a taste pore which is considered an important
      criterion for the morphological maturation of taste buds is not enough for the
      onset of the taste transduction, which necessitates also mature taste cells.
      Moreover, the earlier maturation of palatal taste buds compared with the
      contiguous populations in the oral cavity evokes an evidence of their significant
      role in the transmission of gustatory information, especially in the early life
      of rat.

PMID- 11455536
TI  - Evidence that dopamine-beta-hydroxylase immunoreactive neurons in the lateral
      reticular nucleus project to the spinal cord in the rat.
AB  - The existence of noradrenergic projections from the lateral reticular nucleus
      (LRt) to the dorsal quadrant of cervical, thoracic, or lumbar spinal cord was
      investigated using a combined method of WGA-apo-HRP-gold retrograde tracing and
      dopamine-beta-hydroxylase (DBH) immunocytochemistry. Preliminary retrograde
      tracing studies indicated that LRt neurons projecting to cervical, thoracic, or
      lumbar spinal cord were characteristically located near the perimeter of the LRt.
      Double-labeling experiments demonstrated that a portion of these peripherally
      located, spinal-projecting neurons were DBH-immunoreactive. Double-labeled
      neurons were also located at the parvocellular division of the contralateral LRt
      in the thoracic injection cases. Double-labeled neurons were not observed at the
      subtrigeminal division in cervical, thoracic, or lumbar injection case. The
      results suggest the possibility that the noradrenergic LRt-spinal pathway might
      be involved in a variety of pain processing and cardiovascular regulatory
      functions in the rat.

PMID- 11455537
TI  - The ferret's vomeronasal organ and accessory olfactory bulb: effect of hormone
      manipulation in adult males and females.
AB  - The male ferret, a carnivore, was recently shown to possess a vomeronasal organ
      (VNO). We compared the morphology of the VNO and its associated accessory
      olfactory bulb (AOB) in male and female ferrets that were killed in adulthood.
      The volume and surface area of the VNO neuroepithelium were similar in adult
      gonadectomized male and female ferrets regardless of whether they were treated
      with testosterone propionate (TP) or oil vehicle. An AOB was localized
      bilaterally in the medial caudal part of the olfactory bulbs of adult ferrets
      using soybean agglutin binding and immunostaining for luteinizing hormone
      releasing hormone and tyrosine hydroxylase as well as Nissl staining of coronal,
      horizontal, and sagittal brain sections. There was no effect of sex or TP
      treatment on AOB cell layer volume in adult gonadectomized animals. We found the
      ferret's AOB to be more medially located and much smaller than previously
      reported in this species, thus highlighting the importance of using several
      histochemical markers to characterize this structure in any previously unexamined
      species. Adult male and female ferrets both have a VNO and an associated AOB.
      More research is needed to determine what role, if any, this accessory olfactory
      system plays in mediating behavioral and neuroendocrine responses to pheromones
      in ferrets of either sex.

PMID- 11455538
TI  - Luminal morphology of the avian lower intestine: evidence supporting the
      importance of retrograde peristalsis for water conservation.
AB  - Tissue from the lower intestine of two species of sparrow, the house sparrow
      Passer domesticus and savannah sparrow Passerculus sandwichensis was sectioned in
      an unbiased manner and examined quantitatively using stereology. The tissue was
      processed for light microscopy, and scanning and transmission electron microscopy
      to examine the extent to which microvilli enhanced the epithelial surface area of
      the cecae, rectum, and coprodeum. Parameters measured included individual
      microvillus surface area, microvilli packing density, and absolute surface area.
      In both species, the average surface area, packing density, and absolute surface
      area of microvilli decreased distally along the rectum and coprodeum. All three
      measured variables were not statistically significant (P > 0.05) between species.
      Surface area amplification on the cecae due to microvilli was low, and
      approximated values equivalent to distal regions of the rectum and coprodeum. In
      the cecae, microvilli within the savannah sparrow had a significantly higher (P <
      0.05) individual surface area, packing density, and absolute surface area than in
      the house sparrow. The functional implications of a change in microvilli
      population are discussed in relation to retrograde peristalsis within the lower
      intestine of birds.

PMID- 11455539
TI  - Sound-generating and -detecting motor system in catfish: design of swimbladder
      muscles in doradids and pimelodids.
AB  - Catfishes have evolved a diversity of swimbladder muscles serving in the
      generation of different sounds and probably other acoustic functions. In order to
      find out if anatomical and acoustical differences are parallelled by fine
      structural differences, I examined the sonic muscles of the doradid Platydoras
      and the pimelodid Pimelodus by gross dissections and ultrastructural methods. In
      Platydoras, the sound-generating (drumming) muscle (DM) inserts on a dorsal bony
      plate that vibrates the swimbladder. In pimelodids, the large DM attaches
      directly on the ventral surface of the swimbladder, whereas the small tensor
      tripodis muscle (TT) inserts on the rostral surface near the tripus, the most
      caudal Weberian ossicle. Fibers of all three muscles possess an extensive
      development of sarcoplasmatic reticulum (SR) in association with very thin
      myofibrils (MF) but differed widely in their arrangement. In Platydoras, ribbons
      of MFs are arranged radially around a central core. Mitochondria were found
      within the core and the peripheral sarcoplasm. Pimelodus does not have a
      differentiated core and the cross-sectional area of DM-MFs is about 15% larger as
      determined by stereological measurements. The TT possesses shorter sarcomeres and
      more mitochondria than DMs, which were primarily found between MFs. This suggests
      faster contraction properties and greater resistance to fatigue compared with
      sonic muscles. Data indicate that the higher amount of DM-myofibrils in
      pimelodids might result in stronger muscle contractions and, presumably, in
      higher sound intensities. The fine structure of the TT reveals that contractions
      most likely prevent transmission of swimbladder vibrations to the inner ear via
      the Weberian ossicles during vocalization.

PMID- 11455540
TI  - Elevated expression of Nkx-2.5 in developing myocardial conduction cells.
AB  - A number of different phenotypes emerge from the mesoderm-derived cardiomyogenic
      cells of the embryonic tubular heart, including those comprising the cardiac
      conduction system. The transcriptional regulation of this phenotypic divergence
      within the cardiomyogenic lineage remains poorly characterized. A relationship
      between expression of the transcription factor Nkx-2.5 and patterning to form
      cardiogenic mesoderm subsequent to gastrulation is well established. Nkx-2.5 mRNA
      continues to be expressed in myocardium beyond the looped, tubular heart stage.
      To investigate the role of Nkx-2.5 in later development, we have determined the
      expression pattern of Nkx-2.5 mRNA by in situ hybridization in embryonic chick,
      fetal mouse, and human hearts, and of Nkx-2.5 protein by immunolocalization in
      the embryonic chick heart. As development progresses, significant nonuniformities
      emerge in Nkx-2.5 expression levels. Relative to surrounding force-generating
      ("working") myocardium, elevated Nkx-2.5 mRNA signal becomes apparent in the
      specialized cells of the conduction system. Similar differences are found in
      developing chick, human, and mouse fetal hearts, and nuclear-localized Nkx-2.5
      protein is prominently expressed in differentiating chick conduction cells
      relative to adjacent working myocytes. This tissue-restricted expression of Nkx
      2.5 is transient and correlates with the timing of spatio-temporal recruitment of
      cells to the central and the peripheral conduction system. Our data represent the
      first report of a transcription factor showing a stage-dependent restriction to
      different parts of the developing conduction system, and suggest some commonality
      in this development between birds and mammals. This dynamic pattern of expression
      is consistent with the hypothesis that Nkx-2.5, and its level of expression, have
      a role in regulation and/or maintenance of specialized fate selection by
      embryonic myocardial cells.

PMID- 11455541
TI  - Prenatal development of the human mandible.
AB  - In an effort to better understand the interrelationship of the growth and
      development pattern of the mandible and condyle, a sequential growth pattern of
      human mandibles in 38 embryos and 111 fetuses were examined by serial
      histological sections and soft X-ray views. The basic growth pattern of the
      mandibular body and condyle appeared in week 7 of fertilization. Histologically,
      the embryonal mandible originated from primary intramembranous ossification in
      the fibrous mesenchymal tissue around the Meckel cartilage. From this initial
      ossification, the ramifying trabecular bones developed forward, backward and
      upward, to form the symphysis, mandibular body, and coronoid process,
      respectively. We named this initial ossification site of embryonal mandible as
      the mandibular primary growth center (MdPGC). During week 8 of fertilization, the
      trabecular bone of the mandibular body grew rapidly to form muscular attachments
      to the masseter, temporalis, and pterygoid muscles. The mandible was then rapidly
      separated from the Meckel cartilage and formed a condyle blastema at the
      posterior end of linear mandibular trabeculae. The condyle blastema, attached to
      the upper part of pterygoid muscle, grew backward and upward and concurrent
      endochondral ossification resulted in the formation of the condyle. From week 14
      of fertilization, the growth of conical structure of condyle became apparent on
      histological and radiological examinations. The mandibular body showed a
      conspicuous radiating trabecular growth pattern centered at the MdPGC, located
      around the apical area of deciduous first molar. The condyle growth showed
      characteristic conical structure and abundant hematopoietic tissue in the marrow.
      The growth of the proximal end of condyle was also approximated to the MdPGC on
      radiograms. Taken together, we hypothesized that the MdPGC has an important
      morphogenetic affect for the development of the human mandible, providing a
      growth center for the trabecular bone of mandibular body and also indicating the
      initial growth of endochondral ossification of the condyle.

PMID- 11455542
TI  - Expression of HNK1 epitope by the cardiomyocytes of the early embryonic chick: in
      situ and in vitro studies.
AB  - Monoclonal antibody HNK1 reacts with a carbohydrate epitope in cell surface
      glycoproteins and glycolipids. During development, in various species the HNK1
      epitopes are expressed in migrating neural crest cells and in the developing
      conduction cardiomyocytes. The conduction system is generally thought to be
      developed from cardiomyocytes, but some investigators have hypothesized that it
      is derived from the neural crest because conduction myocytes express neural
      antigens, including HNK1. Using immunohistochemistry, we examined the
      spatiotemporal expression of HNK1 in early chick cardiogenesis (stages 4 to 18)
      and whether cultured precardiac mesoderm does or does not express HNK1 as well as
      sarcomeric myosin (MF20). HNK1 was first expressed in the premyocardium at stage
      8. At stage 10, HNK1-positive cardiomyocytes were scattered along the straight
      heart tube. By stage 18, HNK1-positive cardiomyocytes had become restricted to
      the atrium and sinus venosus. Atrioventricular cushion mesenchyme also expressed
      an HNK1 epitope. Immunostaining of HNK1 and MF20 in cultured precardiac mesoderm
      showed that there are at least three types of cells: 1) cardiomyocytes without
      HNK1 expression, 2) cells possessing both HNK1- and MF20-immunoreactivity, and 3)
      mesenchymal cells with HNK1. Immunogold electron microscopy showed that
      cardiomyocytes containing sparsely distributed myofibrils associated with the Z
      band react with anti-HNK1 antibody. Our observations showed a direct evidence for
      the first time that the precardiac mesoderm generates HNK1-positive
      cardiomyocytes with morphological features similar to those of conduction
      cardiomyocytes.

PMID- 11455543
TI  - Editorial: current developments in computational studies of peptides.

PMID- 11455544
TI  - Determination of conformational equilibrium of peptides in solution by NMR
      spectroscopy and theoretical conformational analysis: application to the
      calibration of mean-field solvation models.
AB  - Peptides occur in solution as ensembles of conformations rather than in a fixed
      conformation. The existing energy functions are usually inadequate to predict the
      conformational equilibrium in solution, because of failure to account properly
      for solvation, if the solvent is not considered explicitly (which is usually
      prohibitively expensive). NMR data are therefore widely incorporated into
      theoretical conformational analysis. Because of conformational flexibility,
      restrained molecular dynamics (with restraints derived from NMR data), which is
      usually applied to determine protein conformation is of limited use in the case
      of peptides. Instead, (a) the restraints are averaged within predefined time
      windows during molecular dynamics (MD) simulations (time averaging), (b) multiple
      copy MD simulations are carried out and the restraints are averaged over the
      copies (ensemble averaging), or (c) a representative ensemble of sterically
      feasible conformations is generated and the weights of the conformations are then
      fitted so that the computed average observables match the experimental data
      (weight fitting). All these approaches are briefly discussed in this article. If
      an adequate force field is used, conformations with large statistical weights
      obtained from the weight-fitting procedure should also have low energies, which
      can be implemented in force field calibration. Such a procedure is particularly
      attractive regarding the parameterization of the solvation energy in nonaqueous
      solvents, e.g., dimethyl sulfoxide, for which thermodynamic solvation data are
      scarce. A method for calibration of solvation parameters in dimethyl sulfoxide,
      which is based on this principle was recently proposed by C. Baysal and H.
      Meirovitch (Journal of the American Chemical Society, 1998, Vol. 120, pp. 800-
      812), in which the energy gap between the conformations compatible with NMR data
      and the alternative conformations is maximized. In this work we propose an
      alternative method based on the principle that the best-fitting statistical
      weights of conformations should match the Boltzmann weights computed with the
      force field applied. Preliminary results obtained using three test peptides of
      varying conformational mobility: H-Ser(1)-Pro(2)-Lys(3)-Leu(4)-OH, Ac-Tyr(1)-D
      Phe(2)-Ser(3)-Pro(4)-Lys(5)-Leu(6)-NH(2), and cyclo(Tyr(1)-D-Phe(2)-Ser(3)-Pro(4)
      Lys(5)-Leu(6)) are presented.

PMID- 11455545
TI  - Generalized-ensemble algorithms for molecular simulations of biopolymers.
AB  - In complex systems with many degrees of freedom such as peptides and proteins,
      there exists a huge number of local-minimum-energy states. Conventional
      simulations in the canonical ensemble are of little use, because they tend to get
      trapped in states of these energy local minima. A simulation in generalized
      ensemble performs a random walk in potential energy space and can overcome this
      difficulty. From only one simulation run, one can obtain canonical-ensemble
      averages of physical quantities as functions of temperature by the single
      histogram and/or multiple-histogram reweighting techniques. In this article we
      review uses of the generalized-ensemble algorithms in biomolecular systems. Three
      well-known methods, namely, multicanonical algorithm, simulated tempering, and
      replica-exchange method, are described first. Both Monte Carlo and molecular
      dynamics versions of the algorithms are given. We then present three new
      generalized-ensemble algorithms that combine the merits of the above methods. The
      effectiveness of the methods for molecular simulations in the protein folding
      problem is tested with short peptide systems.

PMID- 11455546
TI  - Rapid boundary element solvation electrostatics calculations in folding
      simulations: successful folding of a 23-residue peptide.
AB  - Solvation effects play a profound role in the energetics of protein folding.
      While a continuum dielectric model of solvation may provide a sufficiently
      accurate estimate of the solvation effects, until now this model was too
      computationally expensive and unstable for folding simulations. Here we proposed
      a fast yet accurate and robust implementation of the boundary element solution of
      the Poisson equation, the REBEL algorithm. Using our earlier double-energy
      scheme, we included for the first time the mathematically rigorous continuous
      REBEL solvation term in our Biased Probability Monte Carlo (BPMC) simulations of
      the peptide folding. The free energy of a 23-residue beta beta alpha-peptide was
      then globally optimized with and without the solvation electrostatics
      contribution. An ensemble of beta beta alpha conformations was found at and near
      the global minimum of the energy function with the REBEL electrostatic solvation
      term. Much poorer correspondence to the native solution structure was found in
      the "control" simulations with a traditional method to account for solvation via
      a distance-dependent dielectric constant. Each simulation took less than 40 h (21
      h without electrostatic solvation calculation) on a single Alpha 677 MHz CPU and
      involved more than 40,000 solvation energy evaluations. This work demonstrates
      for the first time that such a simulation can be performed in a realistic time
      frame. The proposed procedure may eliminate the energy evaluation accuracy
      bottleneck in folding simulations.

PMID- 11455547
TI  - Simulations of the bis-penicillamine enkephalin in sodium chloride solution: a
      parameter study.
AB  - A simulation study of DPDPE in sodium chloride solution has been performed and
      compared with previous simulations using a different interaction potential for
      the ions. Both global thermodynamics as well as a characterization of association
      to DPDPE have been calculated. We show that the parameters used for the ions have
      a profound effect on the association to the peptide in 1M NaCl. The observed
      differences suggest that individual associations in these and previous
      simulations are sensitive to parameters.

PMID- 11455548
TI  - Ab initio modeling of small, medium, and large loops in proteins.
AB  - This study presents different procedures for ab initio modeling of peptide loops
      of different sizes in proteins. Small loops (up to 8--12 residues) were generated
      by a straightforward procedure with subsequent "averaging" over all the low
      energy conformers obtained. The averaged conformer fairly represents the entire
      set of low-energy conformers, root mean square deviation (RMSD) values being from
      1.01 A for a 4-residue loop to 1.94 A for an 8-residue loop. Three-dimensional
      (3D) structures for several medium loops (20--30 residues) and for two large
      loops (54 and 61 residues) were predicted using residue-residue contact matrices
      divided into variable parts corresponding to the loops, and into a constant part
      corresponding to the known core of the protein. For each medium loop, a very
      limited number of sterically reasonable C(alpha) traces (from 1 to 3) was found;
      RMSD values ranged from 2.4 to 5.9 A. Single C(alpha) traces predicted for each
      of the large loops possessed RMSD values of 4.5 A. Generally, ab initio loop
      modeling presented in this work combines elements of computational procedures
      developed both for protein folding and for peptide conformational analysis.

PMID- 11455549
TI  - Sentinel lymph node biopsy as an alternative to routine axillary lymph node
      dissection in breast cancer patients.

PMID- 11455550
TI  - Sentinel node biopsy is not an alternative to axillary dissection in breast
      cancer.

PMID- 11455551
TI  - Gamma probe-directed lymphatic mapping and sentinel lymphadenectomy in primary
      melanoma: Reliability of the procedure and analysis of failures after long-term
      follow-up.
AB  - BACKGROUND AND OBJECTIVES: Some patients presenting with cutaneous malignant
      melanoma without palpable adenopathy have regional metastatic disease. The
      results of a prospective clinical study of gamma probe-directed sentinel lymph
      node (SLN) biopsy are presented. METHODS: Over a 3-year period, 103 patients with
      a diagnosis of invasive primary cutaneous malignant melanoma (Breslow > 0.12 mm
      or > Clark level II) underwent preoperative lymphoscintigraphy with technetium
      sulfur colloid followed by gamma-probe-guided sentinel lymphadenectomy. There
      were 46 women and 57 men with a mean age of 55.7 years (range, 19-91). RESULTS:
      Mean Breslow thickness was 2.3 mm (range, 0.12-10 mm). Primary locations were
      head and neck in 12, trunk 46, upper extremity 19, and lower extremity in 26. One
      hundred sixteen lymph node basins were mapped in 103 patients. Axillary,
      inguinal, and cervical nodal basins comprised 55, 34, and 11% of the total basins
      evaluated, respectively. Sixty-eight patients (66%) underwent lymphatic mapping
      of one regional nodal basin, 27 patients (26%) underwent synchronous lymphatic
      mapping of 2 regional nodal basins, 6 patients (6%) underwent synchronous
      lymphatic mapping of 3 regional nodal basins, and 2 patients (2%) underwent
      synchronous lymphatic mapping of 4 regional nodal basins. Seroma or infection did
      not occur in any patients. Micrometastatic disease was identified in 15 sentinel
      lymph node biopsy sites in 13 (10%) patients. Of 10 patients undergoing lymph
      node dissection, 9(90%) had no additional pathological lymph node involvement. We
      achieved 99% success rate, 1% rate of failed sentinel node procedure, and 8%
      false-negative rate after median follow-up for 2 years. CONCLUSIONS: We concluded
      that gamma probe-directed sentinel lymph node biopsy is a straightforward
      procedure which can be done in the outpatient setting and facilitates management
      of patients with cutaneous malignant melanoma. It allows the surgeon to identify
      all basins at risk for metastatic disease and the location of the sentinel
      node(s) in relation to the basin.

PMID- 11455552
TI  - Follow-up of sentinel node negative breast cancer patients without axillary lymph
      node dissection.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the
      feasibility of sentinel lymph node biopsy in breast cancer patients at our
      institution and to report the follow-up status of node-negative patients with
      removal of only the sentinel node. METHODS: A total of 247 breast cancer patients
      underwent sentinel node (SN) mapping between June of 1996 and September of 2000.
      The SN was identified by using a combination of vital blue dye and a radiolabeled
      colloid. RESULTS: A SN was identified in 227 of 247 patients (91.9%). One hundred
      forty-five were SN negative, 82 were SN positive. All SN-positive patients
      underwent axillary dissection of level I and II, whereas 83 patients with a
      negative SN had SN biopsy only. Median follow-up of these patients at 22 months
      revealed no axillary recurrence; the morbidity resulting from SN biopsy was
      negligible. CONCLUSIONS: Although the follow-up is very short, SN biopsy only in
      node-negative breast cancer patients had no negative impact on the axillary
      failure rate and resulted in negligible morbidity.

PMID- 11455553
TI  - Molecular markers in Paget disease of the breast.
AB  - BACKGROUND AND OBJECTIVES: Molecular markers are increasingly being analyzed in
      tumor specimens because of their relevance to both prognosis and choice of
      therapy. Paget disease of the breast is an uncommon form of breast cancer, in
      which molecular markers have not been well characterized. The objective of this
      study was to investigate the expression of c-erbB-2, p53, Ki-67, Cyclin D1, Bcl
      2, estrogen receptors (ER), and progesterone receptors (PR) in mammary Paget
      disease. METHODS: Archival tumor tissues from 14 patients diagnosed between 1990
      and 1999 with Paget disease of the breast were analyzed for these molecular
      markers by using an automated immunohistochemical assay. Both the intraepidermal
      Paget cells and the underlying carcinoma were assessed for these markers.
      RESULTS: The majority of Paget cells were positive for c-erbB-2 (92.9%), Cyclin
      D1 (100%), and Ki-67 (85.7%), but very few were positive for Bcl-2 (14.3%). p53
      was overexpressed in 42.9% of the cases, and only 28.6% were positive for ER and
      PR. The rate of expression of these biologic markers was similar in both the
      Paget cells and the underlying intraductal and/or ductal carcinoma cells.
      CONCLUSIONS: Tumors from patients with Paget disease of the breast were positive
      for c-erbB-2, Cyclin D1, and Ki-67, molecular markers commonly associated with
      more aggressive tumor behavior and poorer survival in breast cancer patients. Few
      of these tumors expressed Bcl-2 or ER and PR, which are generally associated with
      a better prognosis. Similar expression of these markers in both Paget cells and
      the underlying carcinoma supports the theory that these cells are the result of
      an intraepidermal spread of ductal carcinoma.

PMID- 11455554
TI  - Management of primary cutaneous melanoma of the head and neck: The University of
      Colorado experience and a review of the literature.
AB  - BACKGROUND: While elective lymph node dissection (ELND), adjuvant radiation
      therapy and sentinel lymph node biopsy have all been advocated in the routine
      management of primary cutaneous melanoma arising in the head and neck, the
      optimal management has not been defined. METHODS: We have reviewed our experience
      of 273 patients with primary melanoma of the head and neck entered into a
      prospective database at the University of Colorado Health Sciences Center (UCHSC)
      from 1978 through 1998 and contrasted this with other reports in the literature.
      RESULTS: A total of 168 patients were identified that received their initial
      management at UCHSC and had no clinical evidence of distant disease. Only nine
      patients (5%) underwent ELND, and no patients received adjuvant radiation
      therapy. The local recurrence rate and 5-year melanoma specific survival,
      according to Breslow thickness, were similar to centers where adjuvant radiation
      therapy or ELND are routinely performed. Our preliminary experience and a review
      of the literature suggests that the technique of sentinel lymph node biopsy is an
      accurate and low risk procedure that provides valuable prognostic information
      useful in the further management of these patients. CONCLUSIONS: There is no
      clear indication that either ELND or adjuvant radiation therapy impacts on the
      outcome of patients with primary melanoma of the head and neck. Sentinel lymph
      node biopsy, in appropriate cases, is becoming the standard of care.

PMID- 11455556
TI  - Micro-lymph node metastasis and its correlation with cathepsin D expression in
      early gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Limited operations for early gastric cancer (EGC) have
      been recommended based on data from lymph node (LN) metastasis detected by
      hematoxylin and eosin (HE) staining. Recently, the clinical importance of micro
      LN metastasis has been reported. In this study, the indication of limited
      operations for EGC was re-evaluated based on the data from micro-LN metastasis
      detected by cytokeratin (CK) immunostaining. Also, the correlation between micro
      LN metastasis and lysosomal acidic protease cathepsin D (CD) expression in
      primary tumors was evaluated. METHODS: A total of 5,949 LNs from 160 patients
      with EGC were stained by anti-CK monoclonal antibody (CAM 5.2). Also, the 160
      primary EGCs were stained by CD. RESULTS: The incidence of LN metastasis
      increased from 7.5% (12/160) by HE-staining to 27.5% (44 of 160) by CK
      immunostaining. The incidence of micro-LN metastasis increased according to the
      depth of tumor invasion (mucosal cancer: 19% and submucosal cancer: 36.8%) and
      the size of tumors (< or = 1.0 cm: 5.9%, 1.1-2.0 cm: 25.6%, and > 2.1 cm: 31.7%).
      The CK-staining patterns were classified into the three subgroups (CK-negative, n
      = 116; single cell type, n = 27; and clustered type, n = 17). The occurrence of
      cancer recurrence was significantly higher in clustered type (17.6%) than in
      single cell type (3.7%) and in CK-negative (0%, P < 0.0001). The mean percentage
      of CD-positive cancer cells of primary tumors in clustered type (17.2%) was
      significantly higher than in single cell type (12.3%) and in CK-negative (7.5%, P
      = 0.0036). CONCLUSIONS: The acidic protease CD may play an important role of
      cancer metastasis in EGC. The limited operation without lymphadenectomy should be
      indicated for EGC with CD-negative.

PMID- 11455557
TI  - Angiomyolipoma of the liver.
AB  - BACKGROUND AND OBJECTIVES: Angiomyolipoma is a rare benign tumor that occurs in
      the liver and other organs. We provide data on eight cases of hepatic
      angiomyolipoma, regarding clinical presentations, diagnoses, management, and
      prognosis. METHODS: A retrospective review of medical records of the eight
      patients with hepatic angiomyolipoma treated at the Chang Gung Memorial Hospital
      Taipei between October 1988 and October 1999. RESULTS: Eight female patients with
      hepatic angiomyolipoma were identified, with ages ranging from 30 to 66 years
      (mean, 45.3 years). Abdominal pain was the most common symptom, occurring in six
      of eight patients (75%). Hepatocellular carcinoma was the most common
      preoperative diagnosis, occurring in three of eight patients (37.5%). Laparotomy
      was performed in seven of eight patients (87.5%). Among these seven patients,
      three patients (43%) received hepatic resection with 100% cure rate to date. One
      of the eight patients (12.5%) was closely follow up after diagnosis made by echo
      guided needle biopsy. CONCLUSIONS: Hepatic angiomyolipoma is a rare and benign
      entity. It has a wide variation and poses a diagnostic challenge clinically,
      radiologically, and pathologically. Its prognosis is good regardless of
      management, including hepatic resection or conservative treatment after tissue
      biopsy by echo-guided needle. To alleviate the mass effect, surgical resection
      may be needed for hepatic angiomyolipoma in selected cases.

PMID- 11455558
TI  - Clinical significance of E-cadherin-catenin complex expression in metastatic foci
      of colorectal carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Reduced expressions of cell adhesion molecules (E
      cadherin, alpha-catenin, and beta-catenin) has been reported to be associated
      with tumor metastasis. However, the clinical significance of such adhesion
      molecules in the metastatic foci remains unclear. In this study, we evaluated the
      prognostic significance of E-cadherin, alpha-catenin, and beta-catenin
      expressions in the metastatic foci of patients with colorectal carcinoma.
      METHODS: The expressions of E-cadherin, alpha-catenin, and beta-catenin were
      detected immunohistochemically in 105 primary tumors, in 30 metastatic lymph
      nodes, and 13 metastatic liver tumors from consecutive patients with colorectal
      carcinoma. RESULTS: Reduced normal expression of E-cadherin, alpha-catenin, and
      beta-catenin in comparison with normal epithelium was detected in 78 primary
      tumors, respectively. Patients who had tumors with reduced expression of adhesion
      molecules showed unfavorable prognosis and the reduced expression of adhesion
      molecules was detected as one of the independent prognostic factors for patients
      with colorectal carcinoma. In 30 patients with lymph node metastasis, the
      increased expression of adhesion molecules in metastatic lymph nodes compared
      with primary tumors was detected in 13 patients. The prognosis of these 13
      patients was poorer than that of remaining 17 patients (P = 0.0296). Also, in 13
      patients with liver metastasis, even no significant difference was observed, the
      mean survival time of 6 patients who had metastatic liver tumors with increased
      expression of adhesion molecules (10 months) was shorter than that of the
      remaining 7 patients (16 months; P = 0.1718). CONCLUSIONS: These results suggest
      that increased expression of the cadherin-catenin cell-cell adhesion system in
      metastatic foci may play an important role in progression of metastatic
      colorectal carcinomas.

PMID- 11455559
TI  - Lung cancer in patients younger than 40 years of age.
AB  - BACKGROUND AND OBJECTIVES: We investigated whether the clinicopathologic
      characteristics and prognosis of lung cancer in younger patients differ from
      those of older patients. METHODS: Among 2,763 lung cancer patients treated during
      the period from April of 1972 to April of 1997, we retrospectively investigated
      the clinical features and prognosis of 53 patients under 40 years of age (young
      group) and compared them with the findings of 1,886 patients with 60 years of age
      or older (elderly group). RESULTS: The proportion of female patients in the
      younger group was significantly higher than that in the elderly group (39.6% vs.
      24.1%). The young group had a significantly higher proportion of adenocarcinoma
      (75.5% vs. 44.8%) and stage III-IV disease (73.6% vs. 59.2%) and a significantly
      lower proportion of squamous cell carcinoma (3.8% vs. 32.1%). Regarding the
      selection of therapy, in the young group, a significantly lower proportion of
      patients underwent surgical therapy (35.8% vs. 41.5%) and a significantly higher
      proportion of those (37.7% vs. 16.4%) received chemotherapy. The overall survival
      between the young and elderly groups was not significantly different. Moreover,
      the 5-year survival rate of the patients undergoing a surgical resection was
      56.1% in the young group and 44.8% in the elderly group (P = 0.0615).
      CONCLUSIONS: This study suggests that the prognosis of young patients with lung
      cancer is at least equivalent to that of older patients; therefore, they should
      be managed according to the general therapeutic guidelines.

PMID- 11455560
TI  - Successful reconstruction using a proximal gastric tube for synchronous
      carcinomas of the esophagus and the stomach.

PMID- 11455561
TI  - Endoscopic hemithyroidectomy and prophylactic lymph node dissection for
      micropapillary carcinoma of the thyroid by using a totally gasless anterior neck
      skin lifting method.

PMID- 11455562
TI  - Electrospray ionization mass spectrometry of oligonucleotide complexes with
      drugs, metals, and proteins.
AB  - I. Introduction 61 II. Binding of Small Molecules to DNA 62 A. Covalent Binding
      62 B. Reversible (Noncovalent) DNA-Binding Agents 65 III. DNA-Metal Ion Complexes
      67 A. Platinum Complexes 70 B. Other Metal Ions 73 IV. DNA-Protein Complexes 74
      A. Introduction 74 B. ESI-MS of DNA-Protein Complexes 76 C. ESI-MS Analysis of
      Proteolytic Products of DNA-Protein Complexes 79 D. ESI-MS of Ternary DNA-Protein
      Ligand Complexes 80 V. Conclusions 80 Abbreviations 81 References 81 -
      Interactions of DNA with drugs, metal ions, and proteins are important in a wide
      variety of biological processes. With the advent of electrospray ionization (ESI)
      and matrix-assisted laser desorption ionization (MALDI), mass spectrometry (MS)
      is now a well-established tool for the characterization of the primary structures
      of biopolymers. The gentle nature of the ESI process, however, means that ESI-MS
      is also finding application for the study of noncovalent and other fragile
      biomolecular complexes. We outline here the progress, to date, in the use of ESI
      MS for the study of noncovalent drug-DNA and protein-DNA complexes together with
      strategies that can be employed to examine the binding of small molecules and
      metal complexes to DNA. In the case of covalent complexes with DNA, sequence
      information can be derived from ESI-MS used in conjunction with tandem mass
      spectrometry (MS/MS) and/or enzymatic digestion. MS/MS can also be used to probe
      the relative binding affinities of drugs that bind to DNA via noncovalent
      interactions. Overall, the work in this area, to date has demonstrated that ESI
      MS and MS/MS will prove to be valuable complements to other structural methods,
      offering advantages in terms of speed, specificity, and sensitivity. (c) 2001
      John Wiley & Sons, Inc.

PMID- 11455563
TI  - New trends in the application of electron ionization to liquid chromatography
      mass spectrometry interfacing.
AB  - I. Introduction 88 II. Cap-EI Interface 90 A. Interface Performance 92 III.
      Direct-EI Interface 93 A. Interface Performance 97 IV. Conclusions 103
      Acknowledgments 103 References 103 --Two recent approaches for coupling capillary
      scale liquid chromatography and electron ionization mass spectrometry are
      reviewed and discussed. The first one, Cap-EI, is the latest evolution of the
      micro-scale particle beam interface, in which the nebulizer has been optimized to
      overcome the limitations of the former approach, in terms of sensitivity and
      linearity. It can be easily hosted in pre-existing instruments without major
      modifications and can use helium and the less-expensive nitrogen to generate
      library-matchable electron ionization spectra. The second one is a miniaturized
      interface for nano- and micro-HPLC, in which the interfacing process takes place
      into a suitably modified ion source. Because the eluate from the column is
      completely transferred into the ion source for ionization, superior sensitivity,
      linearity, and reproducibility are obtained. No signs of chemical ionization are
      observed at flow rates up to 1.5 microL/min. These two interfaces demonstrate
      that electron ionization can be successfully used for the analysis of small
      medium molecules of various polarities, and also at the trace level. The
      possibility to record library-matchable electron ionization spectra offers the
      analyst a powerful tool that can be particularly useful in real-world
      applications.

PMID- 11455564
TI  - Selected reviews on mass spectrometric topics.

PMID- 11455565
TI  - Nuclear Ras: unexpected subcellular distribution of oncogenic forms.
AB  - The Harvey-ras gene encodes small guanine nucleotide binding proteins, mutant
      forms of which are associated with a number of human malignancies. Based on
      studies with truncated forms of the protein it is known that correct post
      translational processing of Ras is essential for cytoplasmic membrane
      localization and function. Surprisingly, immunofluorescence analysis provided
      evidence that in addition to its cytosolic localization, activated H-Ras(Val 12)
      was also localized in the nuclei of transformed cells both in vitro and in vivo.
      Immunoblot analysis of nuclear fractions was consistent with results found by
      immunohistochemistry. Moreover, inhibition of protein farnesylation prevented the
      nuclear targeting of activated H-Ras(Val 12) and NFkappaB. Alterations in
      subcellular distribution pattern and phosphorylation of the cell cycle inhibitor
      p27, which is involved in Ras driven tumor growth, coincided with nuclear
      localization of H-Ras(Val 12). Proteins are often not functional until they are
      transported to their final destination. Indeed, Ras was found to complex with
      NTF2 a factor involved in nuclear protein import and export. Therefore it is
      suggested that NTF2 is the actual carrier for oncogenic Ras. In view of these
      observations the question arises whether the nuclear localization of H-Ras(Val
      12) in tumors is important in oncogenic activation or whether it is a response to
      apoptosis. J. Cell. Biochem. Suppl. 36: 1-11, 2001.

PMID- 11455566
TI  - Suppressive role of endogenous regucalcin in the enhancement of protein kinase
      activity with proliferation of cloned rat hepatoma cells (H4-II-E).
AB  - The role of endogenous regucalcin, which is a regulatory protein in calcium
      signaling, in the regulation of protein kinase activity in the proliferation of
      the cloned rat hepatoma cells (H4-II-E) was investigated. Hepatoma cells were
      cultured for 6-72 h in the presence of fetal bovine serum (FBS; 1 or 10%). The
      number of cells and protein kinase activity in the 5500 g supernatant of cell
      homogenate was significantly increased 24 and 48 h after the culture with FBS (1
      or 10%); the culture with 10% FBS was potent effect as compared with that of 1%
      FBS. FBS (10%)-increased protein kinase activity preceded a significant elevation
      of cell number of 6 h after culture. Serum stimulation-induced increase in
      protein kinase activity was significantly decreased in the presence of
      trifluoperazine (50 microM), staurosporine (10(-6) M) or genistein (10(-5) M) in
      the enzyme reaction mixture. The presence of anti-regucalcin monoclonal antibody
      (40 or 80 ng/ml) in the reaction mixture caused a significant increase in protein
      kinase activity in the cells cultured with FBS (1 or 10%). This increase was
      completely blocked by addition of regucalcin (10(-6) M), which can reveal an
      inhibitory effect on protein kinase activity. Moreover, the effect of antibody in
      increasing protein kinase activity was significantly inhibited in the presence of
      trifluoperazine, staurosporine, or genistein, indicating that endogenous
      regucalcin has an inhibitory effect on Ca(2+)/calmodulin-dependent protein
      kinase, protein kinase C, and protein tyrosine kinase. The present study suggests
      that endogenous regucalcin plays a suppressive role in the enhancement of various
      protein kinase activities associated with a proliferation of the cloned rat
      hepatoma cells (H4-II-E).

PMID- 11455567
TI  - Nuclear changes in necrotic HL-60 cells.
AB  - Cell death in eukaryotes can occur by either apoptosis or necrosis. Apoptosis is
      characterized by well-defined nuclear changes which are thought to be the
      consequence of both proteolysis and DNA fragmentation. On the other hand, the
      nuclear modifications that occur during necrosis are largely less known. Here, we
      have investigated whether or not nuclear modifications occur during ethanol
      induced necrotic cell death of HL-60 cells. By means of immunofluorescence
      staining, we demonstrate that the patterns given by antibodies directed against
      some nuclear proteins (lamin B1, NuMA, topoisomerase IIalpha, SC-35,
      B23/nucleophosmin) changed in necrotic cells. The changes in the spatial
      distribution of NuMA strongly resembled those described to occur during
      apoptosis. On the contrary, the fluorescent pattern characteristic for other
      nuclear proteins (C23/nucleolin, UBF, fibrillarin, RNA polymerase I) did not
      change during necrosis. By immunoblotting analysis, we observed that some nuclear
      proteins (SAF-A, SATB1, NuMA) were cleaved during necrosis, and in the case of
      SATB1, the apoptotic signature fragment of 70 kDa was also present to the same
      extent in necrotic samples. Caspase inhibitors did not prevent proteolytic
      cleavage of the aforementioned polypeptides during necrosis, while they were
      effective if apoptosis was induced. In contrast, lamin B1 and topoisomerase
      IIalpha were uncleaved in necrotic cells, whereas they were proteolyzed during
      apoptosis. Transmission electron microscopy analysis revealed that slight
      morphological changes were present in the nuclear matrix fraction prepared from
      necrotic cells. However, these modifications (mainly consisting of a rarefaction
      of the inner fibrogranular network) were not as striking as those we have
      previously described in apoptotic HL-60 cells. Taken together, our results
      indicate that during necrosis marked biochemical and morphological changes do
      occur at the nuclear level. These alterations are quite distinct from those known
      to take place during apoptosis. Our results identify additional biochemical and
      morphological criteria that could be used to discriminate between the two types
      of cell death. J. Cell. Biochem. Suppl. 36: 19-31, 2001.

PMID- 11455568
TI  - Effects of 1alpha,25-(OH)(2)D(3) on rat growth zone chondrocytes are mediated via
      cyclooxygenase-1 and phospholipase A(2).
AB  - 1alpha,25-(OH)(2)D(3) mediates its effects on growth zone chondrocytes via rapid
      membrane-associated events as well as through traditional nuclear receptor
      mechanisms. The membrane-associated signaling pathways include rapid production
      of diacylglycerol and activation of protein kinase C (PKC), as well as activation
      of phospholipase A(2) (PLA(2)), increased production of arachidonic acid, and
      increased production of prostaglandins. This study examined the roles of PLA(2)
      and cyclooxygenase (Cox) in the mechanism of action of 1alpha,25-(OH)(2)D(3) in
      these cells to determine whether one or both enzymes catalyze the rate limiting
      step and whether constitutive or inducible Cox is involved. Cultures were
      incubated with 1alpha,25-(OH)(2)D(3) for 9 min to measure PKC or for 24 h to
      measure physiological responses ([(3)H]-thymidine incorporation, alkaline
      phosphatase specific activity, [(35)S]-sulfate incorporation). Based on RT-PCR
      and Northern blot analysis, growth zone chondrocytes expressed mRNAs for both Cox
      1 and Cox-2 and neither Cox was modulated by 1alpha,25-(OH)(2)D(3). To examine
      the role of Cox, the cultures were also treated with resveratrol (a specific
      inhibitor of Cox-1), NS-398 (a specific inhibitor of Cox-2), or indomethacin (a
      general Cox inhibitor). The results showed that Cox-1 inhibition reduced the
      1alpha,25-(OH)(2)D(3)-dependent effects on proliferation, differentiation, and
      matrix production, whereas inhibition of Cox-2 only had an effect on
      proliferation. The effects of Cox inhibition were not rate limiting, based on
      experiments in which PLA(2) was activated with melittin or inhibited with
      quinacrine. However, at least part of the action of 1alpha,25-(OH)(2)D(3) was
      regulated by metabolism of arachidonic acid to prostaglandins. This supports the
      hypothesis that 1alpha,25-(OH)(2)D(3) exerts its effects via more than one
      signaling pathway and that these pathways are interrelated via the modulation of
      PLA(2) as a rate-limiting step. PKC regulation may occur at multiple stages in
      the signal transduction cascade. J. Cell. Biochem. Suppl. 36: 32-45, 2001.

PMID- 11455569
TI  - Regulation of expression of plasminogen activator inhibitor-1 in cultured rat
      osteoblastic cells by osteogenic protein-1 (BMP-7).
AB  - Osteogenic Protein-1 (OP-1), a member of the bone morphogenetic protein (BMP)
      family that belongs to the TGF-beta superfamily, induces bone formation in vivo
      and stimulates the synthesis of biochemical markers characteristic of osteoblast
      phenotypes in vitro. In the present study, effects of OP-1 on the expression of
      the plasminogen activator inhibitor-1 (PAI-1) in fetal rat calvaria (FRC) cells
      were examined. The PAI-1 protein levels in conditioned media of FRC cells treated
      with OP-1 or solvent control were determined by quantitative 2-dimensional
      polyacrylamide gel electrophoresis. The identity of PAI-1 was confirmed by mass
      spectroscopy. OP-1 increased the PAI-1 protein level by about 5-fold after 48 h.
      Northern blot analysis showed that the PAI-1 mRNA level was elevated by OP-1 by
      about 25% compared to the control. The observed increase in the PAI-1 mRNA and
      protein level was regulated post-transcriptionally as supported by the following
      observations: (a) OP-1 did not stimulate the cloned PAI-1 promoter-reporter gene
      activity in transient transfection studies, (b) inhibition of transcription by
      actinomycin D did not change the PAI-1 mRNA level in the OP-1-treated FRC cells,
      and (c) the stability of the PAI-1 mRNA in FRC cells treated with OP-1 was
      increased by about 28% compared to that in the control cells. Hence, the present
      study shows that primary cultures of rat osteoblastic cells synthesize and
      secrete PAI-1 protein and that OP-1 elevates the PAI-1 protein level. At least,
      one of the regulatory mechanism is by stabilizing the PAI-1 mRNA. J. Cell.
      Biochem. Suppl. 36: 46-54, 2001.

PMID- 11455570
TI  - Resveratrol inhibits the proliferation of normal human keratinocytes in vitro.
AB  - Resveratrol, a phytoalexin found in grapes and other plants, is a potent
      antioxidant, anti-inflammatory, and antiproliferative agent that is thought to
      have chemopreventive properties with respect to carcinogenesis. However, the
      antiproliferative effects of resveratrol have been described primarily for
      cultured tumor cells and its effects on the proliferation of normal cells are not
      clear. We evaluated the viability and proliferation of cultured normal human
      keratinocytes (KCs) exposed to resveratrol (0.25-100 microM) for different
      lengths of time (5-72 h) by means of (3)H-thymidine incorporation, direct cell
      counts, and a tetrazolium-based formazan reaction. The first two methods
      indicated that resveratrol, even at low concentrations, induced a time-and
      concentration-dependent inhibition of KC proliferation. However, formazan
      production was actually increased at moderate resveratrol concentrations (10
      microM) and diminished only at higher concentrations. Even brief exposure (5 h)
      of KCs to resveratrol resulted in a concentration-dependent elevation in formazan
      production. This was blocked by ionomycin but was not dependent on Ca(2+). We
      conclude that resveratrol, even at submicromolar concentrations, inhibits the
      proliferation of normal human KCs in vitro and, at higher concentrations (40-100
      microM), is cytotoxic to these cells. J. Cell. Biochem. Suppl. 36: 55-62, 2001.

PMID- 11455571
TI  - Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation.
AB  - Leukemia inhibitory factor (LIF) is a cytokine produced by multiple cell types
      including osteoblasts and which is active on bone metabolism. We have previously
      shown that in a bone nodule forming in vitro model of osteogenesis, the fetal rat
      calvaria (RC) cell model, LIF inhibits osteoblast differentiation, acting on late
      osteoprogenitors and/or early osteoblasts. These results are in contrast to in
      vivo experiments, in which LIF has been found to increase bone formation. To
      resolve this discrepancy, we have tested the effect of LIF on rat bone marrow
      (RBM) stromal cell cultures, an in vitro model encompassing earlier
      osteoprogenitor stages. LIF inhibited cell growth in early, proliferating RBM
      cultures, but increased the culture saturation density. The effect of LIF on bone
      nodule formation in this model was cell density dependent and biphasic.
      Continuous treatment with LIF reduced the number of bone nodules present in
      confluent, more mature cultures, and the inhibitory effect was strongest when
      cells were plated at higher cell density than lower. In contrast, during the
      early stages of RBM culture, nodule numbers were higher in LIF-treated dishes
      than in controls, and this effect was greater in lower density cultures. Acute
      LIF treatment restricted to early time points increased the final number of bone
      nodules formed in mature RBM cell cultures, but not in RC cell cultures. Our
      results indicate that LIF exerts complex, stage-specific effects on
      osteoprogenitor recruitment, differentiation, and bone formation, and that the
      effects are cell nonautonomous, in the rat bone marrow stromal cell model. J.
      Cell. Biochem. Suppl. 36: 63-70, 2001.

PMID- 11455572
TI  - Transcriptional suppression of Sox9 expression in chondrocytes by retinoic acid.
AB  - SOX9 is a transcription factor that is expressed in chondrocytes and regulates
      expression of chondrocyte phenotype related genes. Expression of these genes is
      known to be suppressed by retinoic acid (RA). We, therefore, examined whether the
      Sox9 gene expression is regulated by RA in chondrocytes. RA treatment suppressed
      Sox9 mRNA expression in primary chondrocytes prepared from newborn mouse rib
      cartilage within 12 h and this suppression lasted at least up to 24 h. The RA
      suppression of Sox9 mRNA levels was dose-dependent starting at 0.5 microM with a
      maximum at 1 microM. Nuclear run-on assays revealed that RA reduced the rate of
      transcription of Sox9 gene. Finally, Western blot analysis indicated that RA
      suppressed SOX9 protein levels in these chondrocytes. Furthermore, overexpression
      of SOX9 reversed RA suppression of Col2a1 enhancer activity. These observations
      indicate that RA suppresses Sox9 gene expression in chondrocytes at least in part
      through transcriptional events. J. Cell. Biochem. Suppl. 36: 71-78, 2001.

PMID- 11455573
TI  - TGF-beta1 is the factor secreted by proliferative chondrocytes to inhibit neo
      angiogenesis.
AB  - Growth plate is an avascular tissue, which has been reported to be capable of
      retarding tumor spread. It is believed that angiogenic inhibitor(s) exist to
      inhibit the neo-vascularization of tumor, thus impeding the tumor growth. In this
      study, growth plate chondrocyte-derived TGFbeta1 was identified to be anti
      angiogenic. It was found that growth plate chondrocytes (GPC) secreted TGFbeta1
      mostly in latent form as demonstrated by gel filtration and immunoblotting.
      Enzyme-linked immunosorbent assay (ELISA) was followed to quantify TGFbeta1 in
      GPC conditioned medium (CM), in which 866 pg/ml of TGFbeta1 was found. Besides,
      the angiogenesis inhibitory effect of GPC CM was abolished by the addition of
      anti-TGFbeta1 antibody in the in vitro culture system and the in vivo chick
      chorioallantoic membrane (CAM) assay. This confirmed the anti-angiogenic
      properties of chondrocyte-derived TGFbeta1. TGFbeta1 was expressed predominantly
      in the proliferative zone of porcine growth plate. This explains the low
      incidence of tumor invasion across the entire growth plate. Also, this helps to
      explain the observation that tumor invasion across the physis increases with age
      as the proliferative zone gradually disappears. J. Cell. Biochem. Suppl. 36: 79
      88, 2001.

PMID- 11455574
TI  - Mitogenic signaling by cyclic adenosine monophosphate in chromaffin cells
      involves phosphatidylinositol 3-kinase activation.
AB  - Increase of intracellular cyclic adenosine monophosphate by the permeant cyclic
      adenosine monophosphate analog, 8-(4-chlorophenylthio)-adenosine 3':5'- cyclic
      monophosphate, is mitogenic for normal adult rat chromaffin cells. The mitogenic
      effect is blocked by the phosphatidylinositol 3-kinase inhibitor, LY294002, and
      is associated with accumulation of phosphorylated Akt and p70S6 kinase,
      suggesting that cyclic adenosine monophosphate activates Type l
      phosphatidylinositol 3-kinase. The mechanism of activation was examined in PC12
      pheochromocytoma cells, which are neoplastic chromaffin cells that exhibit many
      of the biochemical characteristics of their normal counterparts. Incubation of
      PC12 cells with 8-(4-chlorophenylthio)-adenosine 3':5'- cyclic monophosphate led
      to a significant increase in total phosphatidylinositol 3-kinase activity that
      was sensitive to low concentrations of LY294002. The increase was maximal at 1 h
      and returned to basal levels within six hours. Immunoprecipitation studies showed
      no increase in phosphatidylinositol 3-kinase activity in anti-phosphotyrosine
      immune complexes from PC12 cells stimulated by 8-(4-chlorophenylthio)-adenosine
      3':5'- cyclic monophosphate, in contrast to cells stimulated by nerve growth
      factor. Instead, activity was demonstrated in association with p110gamma and p85.
      These findings suggest that cyclic adenosine monophosphate causes activation of
      Types IA and IB phosphatidylinositol 3-kinase by a novel mechanism in chromaffin
      and pheochromocytoma cells. That activation may contribute to chromaffin cell
      proliferation and to the development and progression of pheochromocytomas. J.
      Cell. Biochem. Suppl. 36: 89-98, 2001.

PMID- 11455575
TI  - Cyclic strain induces reactive oxygen species production via an endothelial
      NAD(P)H oxidase.
AB  - Vascular endothelial cells are constantly subjected to pressure-induced cyclic
      strain. Reactive oxygen species (ROS) have been implicated in atherosclerosis and
      vascular remodeling. Recent evidence indicates that a vascular NAD(P)H oxidase
      may be an important source of ROS in both physiologic and pathophysiologic
      situations. The aim of this study was to investigate cyclic strain-induced
      NAD(P)H oxidase activity in endothelial cells. ROS production was examined by
      electron paramagnetic resonance and lucigenin chemiluminescence. Cyclic strain
      induced NAD(P)H oxidase activity was quantified by activity assay while the
      expression of p22phox was monitored by Northern blotting. Endothelial cells
      produce basal amounts of ROS that were enhanced by cyclic strain. Moreover
      subsequent stimulation with TNF-alpha resulted in significantly greater ROS
      production in cells previously exposed to cyclic strain as compared to static
      conditions. Cyclic strain resulted in a significant increase in message for the
      p22phox subunit as well as activity of the NAD(P)H oxidase. The induced oxidative
      stress was accompanied by increased mobilization of the transcription factor
      NFkappaB, an effect that was blocked by a pharmacological inhibitor of NAD(P)H.
      These results demonstrate a pivotal role for NAD(P)H oxidase in cyclic strain
      induced endothelial ROS production and may provide insight into the modulation of
      vascular disease by biomechanical forces. J. Cell. Biochem. Suppl. 36: 99-106,
      2001.

PMID- 11455576
TI  - Tacrolimus, but not cyclosporine A, significantly increases expression of ICAM-1
      and IFN-gamma in the NOD mouse.
AB  - We studied the alterations of cytokines and ICAM-1 expression in the NOD mouse
      pancreas produced by the administration of Cyclosporine A (CY) and Tacrolimus
      (TA), two widely used immunosuppressive drugs. Results evidenced differences in
      the effects of these two drugs. In fact, during treatment and after withdrawal,
      CY-treated animals remained euglycemic, showed good islet cell preservation and
      had low levels of Th1 and Th2 cytokines; ICAM-1 positivity within the islets was
      also found to be relatively low. On the other hand, TA-treated animals had
      infiltrated islets containing numerous dendritic cells, adhesion molecule
      overexpression, increased IFN-gamma and ICAM-1 mRNA transcripts, and
      interestingly, high levels of circulating ICAM-1. However, even these animals
      remained euglycemic. These findings lead to the thought that these drugs may
      exert their effects in very different ways. Moreover, in TA-treated animals, the
      presence of an islet infiltrate containing numerous dendritic cells coupled with
      maintenance of euglycemia is suggestive for the involvement of immunosurveillance
      mechanisms. J. Cell. Biochem. Suppl. 36: 107-116, 2001.

PMID- 11455577
TI  - Green fluorescent protein variants fold differentially in prokaryotic and
      eukaryotic cells.
AB  - Better-folding Green Fluorescent Protein (GFP) mutants selected from bacterial
      screenings are commonly used in widely different cellular environments. However,
      it is unclear if the folding efficiency of GFPs is invariant in different cell
      types. In this work, we have analysed the folding properties of GFP variants in
      bacteria versus mammalian cells. Remarkably, S65T was found to fold at comparable
      levels with the wild type GFP in bacteria, but at 10-fold lower levels in
      mammalian cells. On the other hand, Bex1 folded 3-4 times better than the wtGFP
      or S65T in E. coli, and 10-20-fold or more than 95-fold better, respectively, in
      mammalian cells. The Vex1 mutant demonstrated similar properties to Bex1. No
      evidence of differential GFP unfolding in vivo or of preferential degradation of
      unfolded GFP molecules was found. Moreover, no relationship between GFP folding
      efficiency and expression levels, or protein stability was detected. Trivial
      Aconfounding factors, like GFP unfolding caused by different pH or fluorescence
      quenching due to molecular crowding, were also excluded. In summary, our results
      demonstrate that specific GFP variants follow different folding trajectories in
      mammalian versus bacterial cells. The specificity of this differential folding
      supports a role of chaperones in guiding the folding of GFP in vivo. J. Cell.
      Biochem. Suppl. 36: 117-128, 2001.

PMID- 11455578
TI  - Differential expression of human Polycomb group proteins in various tissues and
      cell types.
AB  - Polycomb group proteins are involved in the maintenance of cellular identity. As
      multimeric complexes they repress cell type-specific sets of target genes. One
      model predicts that the composition of Polycomb group complexes determines the
      specificity for their target genes. To study this hypothesis, we analyzed the
      expression of Polycomb group genes in various human tissues using Northern
      blotting and immunohistochemistry. We found that Polycomb group expression varies
      greatly among tissues and even among specific cell types within a particular
      tissue. Variations in mRNA expression ranged from expression of all analyzed
      Polycomb group genes in the heart and testis to no detectable Polycomb group
      expression at all in bone marrow. Furthermore, each Polycomb group gene was
      expressed in a different number of tissues. RING1 was expressed in practically
      all tissues, while HPH1 was expressed in only a few tissues. Also within one
      tissue the level of Polycomb group expression varied greatly. Cell type-specific
      Polycomb group expression patterns were observed in thyroid, pancreas, and
      kidney. Finally, in various developmental stages of fetal kidney, different
      Polycomb group expression patterns were observed. We conclude that Polycomb group
      expression can vary depending on the tissue, cell type, and development stage.
      Polycomb group complexes can only be composed of the Polycomb group proteins that
      are expressed. This implies that with cell type-specific Polycomb group
      expression patterns, cell type-specific Polycomb group complexes exist. The fact
      that there are cell type-specific Polycomb group targets and cell type-specific
      Polycomb group complexes fits well with the hypothesis that the composition of
      Polycomb group complexes may determine their target specificity. J. Cell.
      Biochem. Suppl. 36: 129-143, 2001.

PMID- 11455579
TI  - Estrogen modulates estrogen receptor alpha and beta expression, osteogenic
      activity, and apoptosis in mesenchymal stem cells (MSCs) of osteoporotic mice.
AB  - In the mouse, ovariectomy (OVX) leads to significant reductions in cancellous
      bone volume while estrogen (17beta-estradiol, E2) replacement not only prevents
      bone loss but can increase bone formation. As the E2-dependent increase in bone
      formation would require the proliferation and differentiation of osteoblast
      precursors, we hypothesized that E2 regulates mesenchymal stem cells (MSCs)
      activity in mouse bone marrow. We therefore investigated proliferation,
      differentiation, apoptosis, and estrogen receptor (ER) alpha and beta expression
      of primary culture MSCs isolated from OVX and sham-operated mice. MSCs, treated
      in vitro with 10(-7) M E2, displayed a significant increase in ERalpha mRNA and
      protein expression as well as alkaline phosphatase (ALP) activity and
      proliferation rate. In contrast, E2 treatment resulted in a decrease in ERbeta
      mRNA and protein expression as well as apoptosis in both OVX and sham mice. E2 up
      regulated the mRNA expression of osteogenic genes for ALP, collagen I, TGF-beta1,
      BMP-2, and cbfa1 in MSCs. In a comparison of the relative mRNA expression and
      protein levels for two ER isoforms, ERalpha was the predominant form expressed in
      MSCs obtained from both OVX and sham-operated mice. Cumulatively, these results
      indicate that estrogen in vitro directly augments the proliferation and
      differentiation, ERalpha expression, osteogenic gene expression and, inhibits
      apoptosis and ERbeta expression in MSCs obtained from OVX and sham-operated mice.
      Co-expression of ERalpha, but not ERbeta, and osteogenic differentiation markers
      might indicate that ERalpha function as an activator and ERbeta function as a
      repressor in the osteogenic differentiation in MSCs. These results suggest that
      mouse MSCs are anabolic targets of estrogen action, via ERalpha activation. J.
      Cell. Biochem. Suppl. 36: 144-155, 2001.

PMID- 11455580
TI  - Three-dimensional structural analysis of fibronectin heparin-binding domain
      mutations.
AB  - Using recombinant fibronectin proteins containing the V region and two point
      mutations in the high-affinity heparin-binding domain, we previously showed that
      these domains modulate tumor cell invasion as well as proteinase expression and
      apoptosis in human fibroblasts. Structurally, the wildtype counterparts to these
      two point mutations, together with four other discontinuous, positively charged
      residues, form a cationic cradle in domain III-13 of fibronectin that binds
      heparin. We constructed a three-dimensional model of this cationic cradle and
      determined whether the two engineered point mutations in the heparin-binding
      domain would alter this cradle conformation, thus explaining the altered cell
      behavior. Our model of fibronectin domain III-13 was generated from a template of
      the three-dimensional structure of a homologous (25% identity) domain, III-3,
      from tenascin. The amino acid sequences of III-13 that differed from tenascin III
      3 were replaced, and side chains for positively charged arginines 6 and 7 were
      substituted with uncharged threonines. The model revealed that the two mutated
      threonine residues were solvent accessible, readily accommodated as part of an
      antiparallel beta strand, and remained part of the three-dimensional cradle.
      These models suggest that the two point mutations in the heparin-binding domain
      of fibronectin III-13 alter cell function probably through changes in charge and
      not through changes in the conformational structure of the cationic cradle. J.
      Cell. Biochem. Suppl. 36: 156-161, 2001.

PMID- 11455581
TI  - Zinc-alpha(2)-glycoprotein hinders cell proliferation and reduces cdc2
      expression.
AB  - Zinc-alpha(2)-glycoprotein (Znalpha(2)gp) is widely distributed in body fluids
      and epithelia. Its expression in stratified epithelia increases with
      differentiation. We previously showed that Zn alpha(2)gp has ribonuclease
      activity, and that squamous tumor cells grown on a matrix of Znalpha(2)gp were
      growth-inhibited. Here we demonstrate, both by adding Znalpha(2)gp to the culture
      medium and, more unequivocally, by stably transfecting SiHa cells with
      Znalpha(2)gp cDNA, that the introduction of Znalpha(2)gp into SiHa tumor cells
      reduces proliferation. In response to Znalpha(2)gp, we find an accumulation of
      the cell population in G(2)/M by flow cytometry, paralleling the reduction of
      proliferation. In order to distinguish growth inhibition by cell cycle arrest
      from that produced by apoptosis or differentiation, we examine by RT-PCR how
      Znalpha(2)gp affects the expression of genes commonly used as markers of these
      properties. No changes are observed for PCNA, p53, c-myc, or bcl-2. Only cdc2
      expression responds to Znalpha(2)gp, with a reduction of up to over a factor of
      two. Cdc2 is the only cyclin-dependent kinase regulating the G(2)/M transition
      without redundancy and is required as a rate-limiting step in the cell cycle. Its
      increased expression has been directly linked to increased proliferation and
      decreased differentiation of advanced tumors; conversely, its downregulation by
      Znalpha(2)gp might hinder tumor progression. J. Cell. Biochem. Suppl. 36: 162
      169, 2001.

PMID- 11455582
TI  - Mammalian recombination hot spot in a DNA loop anchorage region: a model for the
      study of common fragile sites.
AB  - We analyzed the replication pattern and the topological organization of a 200 kb
      long Chinese hamster polygenic locus, which spans the boundary of two isochores.
      One of them is G + C rich while the second one is highly A + T rich. Previous
      analysis of mutants amplified for this locus had identified, within the A + T
      rich isochore, a mitotic recombination hotspot and a replication origin separated
      by some 7 kb. The recombination hotspot exhibits structural features repeatedly
      observed at common fragile sites, including a typical enrichment in peaks of
      enhanced DNA helix flexibility. By studying the replication pattern of the same
      locus in the non-amplified CHO cells, we confirm here the localization of the
      replication origin and show that the mitotic recombination hotspot does not
      correspond to a replicon junction. This finding makes questionable current
      hypotheses correlating replication termination regions with recombination prone
      sequences. Using topoisomerase II-mediated DNA cleavage at matrix attachment
      sites, we identified a 40 kb-long DNA anchorage region extending all along a
      transcription unit nested within the A + T rich isochore. Both the recombination
      hotspot and the replication origin lie within this topoisomerase II sensitive
      region, which suggests that features essential for initiation of recombination
      and initiation of DNA replication cluster within DNA anchorage regions. Features
      common to this region and to common fragile sites are discussed. J. Cell.
      Biochem. Suppl. 36: 170-178, 2001.

PMID- 11455583
TI  - Gene regulatory potential of 1alpha,25-dihydroxyvitamin D(3) analogues with two
      side chains.
AB  - The nuclear hormone 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) acts
      through the transcription factor vitamin D receptor (VDR) via combined contact
      with the retinoid X receptor (RXR), coactivator proteins, and specific DNA
      binding sites (VDREs). Ligand-mediated conformational changes of the VDR are the
      core of the molecular switch of nuclear 1alpha,25(OH)(2)D(3) signalling. Studying
      the interaction of 1alpha,25(OH)(2)D(3) analogues with this molecular switch
      should allow the characterization of their potential selective biological
      profile. A 1alpha,25(OH)(2)D(3) analogue with two side chains (Ro27-2310 or
      Gemini) was found to stabilize functional VDR conformations and VDR-RXR
      heterodimers on a VDRE with a slightly lower sensitivity than the natural
      hormone. A 19-nor derivative of Gemini (Ro27-5646) showed similar sensitivity
      whereas 5,6-trans (Ro27-6462) 3-epi (Ro27-5840) and 1alpha-fluoro (Ro27-3752)
      derivatives were equal to each other, but approximately 30-times less sensitive
      than Gemini. A des-C,D derivative of Gemini (Ro28-1909) showed only residual
      activity at maximal concentrations. In contrast to 1alpha,25(OH)(2)D(3), Gemini
      and its derivatives showed a differential preference in stabilizing VDR
      conformations which was found to be modulated by DNA coactivator and corepressor
      proteins. An analysis of the gene regulatory potential of the VDR agonists in
      cellular reporter gene systems demonstrated the same ranking as in the in vitro
      systems, but Gemini and its 19-nor derivative were found to be more sensitive
      than 1alpha,25(OH)(2)D(3) which indicates that the natural hormone is selectively
      metabolized. This study used straightforward methods for the in vitro and ex vivo
      evaluation of the gene regulatory potential of 1alpha,25(OH)(2)D(3) analogues.
      Gemini was highlighted as an interesting drug candidate which could not be
      optimized through obvious chemical modifications in its A-ring. J. Cell. Biochem.
      Suppl. 36: 179-190, 2001.

PMID- 11455584
TI  - Interferon regulatory factor 1 promoter polymorphism and response to type 1
      interferon.
AB  - The clinical success of interferon-treatment has been found to vary in different
      individuals. To explain this, we hypothesized that responses to type 1
      interferons could be partly determined by interferon regulatory factor-1 gene
      transcription, because the latter is an important transcription factor in the
      interferon system. We demonstrated that the antiproliferative effect of type 1
      interferons on human liver cancer cells correlates with levels of transcription
      of the interferon regulatory factor-1 gene in parallel with those of p21(WAF-1)
      expression. Here, we investigated whether mutations in the interferon regulatory
      factor-1 gene cause different responses to type 1 interferons. DNA from several
      human liver cancer cell lines and peripheral blood mononuclear cells was
      investigated. Nucleotide sequences of the interferon regulatory factor-1 gene and
      polymerase chain reaction products of its upstream region were determined
      directly and after cloning. The promoter activity of the upstream region of this
      gene was measured by the luciferase reporter assay. We found 4 point mutations in
      the upstream (- 1 approximately - 495) region, and the luciferase promoter assay
      demonstrated that these mutations did modify promoter activity. Analysis of DNA
      from healthy volunteers showed that these mutations are single nucleotide
      polymorphisms. These results suggest that single nucleotide polymorphisms of the
      interferon regulatory factor-1 promoter contribute, at least in part, to
      determining responses to type 1 interferons. J. Cell. Biochem. Suppl. 36: 191
      200, 2001.

PMID- 11455585
TI  - Differentially induced expression of C-type lectins in activated lymphocytes.
AB  - The human NK gene complex encodes for the leucocyte C-type lectins, CD69, AICL
      (activation-induced C-type lectin), LLT1 (lectin-like transcript), CD161/NKR-P1A,
      CD94, and for NKG-2 molecules. These gene products have been implicated in the
      regulation of the function of natural killer (NK) cells and other lymphocytes. In
      this study the expression of C-type lectins during the early activation of PMA
      stimulated peripheral blood lymphocytes was examined. To investigate the
      influence of de novo protein synthesis on activation-dependent expression of C
      type lectins, cells were cultured in presence of cycloheximide (CHX) and mRNA
      levels were analyzed by semi-quantitative reverse transcription-polymerase chain
      reaction. Upregulated levels of CD69, AICL, and LLT1, but less pronounced changes
      of CD161/NKR-P1A and CD94 mRNA were found at early time points of cellular
      activation. CD69 was superinduced by CHX at the nuclear precursor transcript and
      the mRNA level suggesting that regulation of transcriptional activity and mRNA
      stability contribute to extent of CD69 mRNA accumulation. CHX treatment resulted
      also in an overexpression of AICL, LLT1, and CD161/NKR-P1A mRNAs. Conversely, CHX
      blocked CD94 mRNA expression in PMA-stimulated cells, demonstrating that this
      process is dependent on new protein synthesis. Expression kinetics in context
      with susceptibility to CHX indicate that the mechanisms responsible for
      upregulated CD69, AICL, and LLT1 expression are distinct from those which control
      CD161/NKR-P1A or CD94 expression. J. Cell. Biochem. Suppl. 36: 201-208, 2001.

PMID- 11455586
TI  - S-Adenosylmethionine decarboxylase gene expression is regulated by the cAMP
      signal transduction pathway in H-ras transformed fibrosarcoma cells capable of
      malignant progression.
AB  - The hypothesis that H-ras transformed cells contain alterations in signalling
      pathways important in controlling the expression of S-adenosylmethionine
      decarboxylase, (SAMDC) a highly regulated activity in the biosynthesis of
      polyamines was tested. Mouse 10 T1/2 fibroblasts and H-ras transformed cell lines
      of varying degrees of malignant potential were treated with agents which affect
      cAMP levels within cells. Elevations in SAMDC expression were noted in H-ras
      transformed metastatic C3 cells, which were not observed in either parental, non
      transformed 10 T1/2 fibroblast cells, or in ras transformed NR3 cells, which are
      only capable of benign tumour formation. Forskolin, a stimulator of cAMP
      synthesis, was able to increase SAMDC enzyme activity but the response which
      occurred was dependent upon the cellular phenotype expressed. Actinomycin D pre
      treatment of C3 cells prior to exposure to forskolin did not abrogate the
      elevation observed in SAMDC gene expression suggesting that this was not a
      transcriptional process mediated event. Forskolin pre-treatment of C3 cells did
      result in a marked increase in the half-life of SAMDC mRNA transcripts suggesting
      a role for post-transcriptional stabilization. Furthermore, cycloheximide
      treatment of malignant C3 cells resulted in elevated SAMDC mRNA levels. Treatment
      of malignant C3 cells with both cycloheximide and forskolin together resulted in
      a further additive elevation in SAMDC message levels. Cycloheximide treatment
      alone was found to affect the half-life of SAMDC mRNA through a mechanism of post
      transcriptional stabilization. Additionally, altered SAMDC gene expression in C3
      cells which occurred in response to cAMP alterations, was enhanced by stimulation
      of a protein kinase C pathway suggesting possible interactions between protein
      kinase C-and cAMP-mediated pathways which affect the regulation of SAMDC
      expression in highly malignant C3 cells. These results demonstrate aberrant
      regulation of signalling pathways involved in controlling SAMDC gene expression
      in H-ras transformed cells capable of malignant progression and provide further
      insight into the altered growth regulatory program associated with H-ras mediated
      cellular transformation and malignant progression. J. Cell. Biochem. Suppl. 36:
      209-221, 2001.

PMID- 11455587
TI  - Influence of the Lurcher mutation on myosin heavy chain expression in skeletal
      and cardiac muscles.
AB  - This study evaluated the influence of Lurcher mutation, characterized by
      degeneration of cerebellar Purkinje cells, granule cells, and inferior olive
      neurons, on cardiac and skeletal muscles: one respiratory (diaphragm, Dia), three
      masticatory (anterior temporalis, AT; masseter superficialis, MS and anterior
      digastric, AD), one hind limb (soleus, S), entire tongue (T), and one cardiac
      (ventricle, V) muscles. Body and muscle weight, muscle protein content, and
      myosin heavy chain (MHC) isoforms relative expression were then compared in
      Lurcher mutant mice vs. normal, according to sex. Male body weight was always
      greater than female one, but there was no specific muscle difference in females,
      except for T relative weight which was greater in normal females. Muscle protein
      concentration was greater in normal males except for AD and T in which it was
      lower. Lurcher mutant mice showed a reduced whole body growth but no specific
      muscle atrophy (except in male AT), and a global decrease in muscle protein
      content which made muscles more fragile (except in female Dia and male T, in
      which it was greater). Lurcher mutation induced a global reduction of muscle
      protein concentration whereas a general influence of sex could not be disclosed.
      Concerning MHC relative composition, all the muscles were fast-twitch: Dia, AT,
      MS, AD, S, and T predominantly expressed the fast type 2 MHC isoforms, except
      female S, whereas V contained only MHC alpha, also a fast MHC. Female muscles
      were slower than male ones and classification of muscles in terms of shortening
      velocity was comparable in normal male and female. In other respects, male
      Lurcher mutant muscles were slower and consequently more fatigue resistant than
      normal, except T which became faster and less fatigue resistant. On the contrary,
      in female mutants, only the Dia was slower than normal one, MS and AD were
      comparable to normal ones and finally, AT, S, and T were faster than normal ones.
      It should be noted that a developmental MHC (neonatal) was present in Lurcher AD.
      Motor control, which influences muscle structure, is altered in Lurcher mutant
      and could be one of the causal factor of the fast-to-slow MHC switches observed
      in some mutant muscles. It seems therefore that cerebellar Purkinje cells,
      granule cells, and inferior olive neurons are very important in maintaining the
      structural integrity of both cardiac and skeletal muscle, and their degeneration
      is accompanied by important muscles modifications. J. Cell. Biochem. Suppl. 36:
      222-231, 2001.

PMID- 11455588
TI  - Estrogen suppression of EGFR expression in breast cancer cells: a possible
      mechanism to modulate growth.
AB  - Epidermal growth factor receptor (EGFR) is a transmembrane receptor whose
      overexpression in breast cancer predicts for poor prognosis and is inversely
      correlated with expression of estrogen receptor (ER). This study was designed to
      investigate whether estrogen plays an active role in suppression of EGFR
      expression in estrogen-responsive breast cancer cell lines expressing low levels
      of EGFR. Upon withdrawal of estrogen, EGFR mRNA and protein increased 3-6 fold in
      MCF-7, T47D, and BT474 ER+ breast cancer cells. This was reversible upon addition
      of estradiol back to the culture media, but only after prolonged treatment.
      Nuclear run-on assays and studies with the transcription inhibitor actinomycin D
      demonstrated that regulation is at the transcriptional level. These results
      indicate that in the presence of estrogen, ER+ breast cancer cells possess active
      mechanisms to suppress EGFR expression. Up-regulation of EGFR in response to
      estrogen depletion and growth inhibition could represent an attempt to rescue
      cell growth by utilizing an alternative pathway. Indeed, we found that estrogen
      depleted breast cancer cells are more sensitive to the mitogenic effects of EGF
      and TGF-alpha, and simultaneous blockade of both estrogen and EGFR signaling
      pathways induced cell death. J. Cell. Biochem. Suppl. 36: 232-246, 2001.

PMID- 11455589
TI  - Distinct regions of cyclinT1 are required for binding to CDK9 and for recruitment
      to the HIV-1 Tat/TAR complex.
AB  - Tat-mediated activation of the HIV-1 promoter activity requires Tat-dependent
      recruitment of the cyclinT1/CDK9 complex (P-TEFb) to the transacting element
      (TAR) RNA. Tat interaction with the cyclinT1, the regulatory partner of CDK9,
      results in a specific recruitment of the heterodimer CycT1/CDK9 complex to TAR,
      whereby it promotes transcription elongation of the HIV-1 LTR-mediated
      transcription. Using the yeast two-hybrid protein interaction assay we analyzed
      the binding between cyclinT1 and CDK9. Moreover, using a modified three-hybrid
      yeast interaction system, we analyzed the recruitment of CycT1 to the Tat/TAR
      complex. The data presented here demonstrated that distinct domains of cyclinT1
      interact with CDK9 and Tat/TAR in vivo. These findings will be instrumental for
      the designing of proper dominant-negative P-TEFb components capable to interfere
      with Tat function. J. Cell. Biochem. Suppl. 36: 247-253, 2001.

PMID- 11455590
TI  - Influence of rotational energy barriers to the conformational search of protein
      loops in molecular dynamics and ranking the conformations.
AB  - An adjustable-barrier dihedral angle potential was added as an extension to a
      novel, previously presented soft-core potential to study its contribution to the
      efficacy of the search of the conformational space in molecular dynamics. As
      opposed to the conventional soft-core potential functions, the leading principle
      in the design of the new soft-core potential, as well as of its extension, the
      soft-core and adjustable-barrier dihedral angle (SCADA) potential (referred as
      the SCADA potential), was to maintain the main equilibrium properties of the
      original force field. This qualifies the methods for a variety of a priori
      modeling problems without need for additional restraints typically required with
      the conventional soft-core potentials. In the present study, the different
      potential energy functions are applied to the problem of predicting loop
      conformations in proteins. Comparison of the performance of the soft-core and
      SCADA potential showed that the main hurdles for the efficient sampling of the
      conformational space of (loops in) proteins are related to the high-energy
      barriers caused by the Lennard-Jones and Coulombic energy terms, and not to the
      rotational barriers, although the conformational search can be further enhanced
      by lowering the rotational barriers of the dihedral angles. Finally, different
      evaluation methods were studied and a few promising criteria found to distinguish
      the near-native loop conformations from the wrong ones.

PMID- 11455591
TI  - Pressure effect on denaturant-induced unfolding of hen egg white lysozyme.
AB  - The influence of hydrostatic pressure (< or =100 MPa) on denaturant-induced
      unfolding of hen egg white lysozyme was investigated by means of ultraviolet
      spectroscopy at various temperatures. Assuming a two-state transition model, the
      dependence of Gibbs free-energy change of unfolding on the denaturant
      concentration was calculated. Under applied hydrostatic pressure, these data were
      interpreted as suggesting that a two-state model is not applicable in a
      restricted temperature range; the dominant effect of hydrostatic pressure is to
      affect the cooperativity in protein unfolding due to a chemical equilibrium shift
      in the direction of the reduction in the system volume. The deviation from the
      two-state transition model appears to be rationalized by assuming that applied
      pressure induces an intermediate conformation between the native and unfolded
      states of the protein. The implication of the thermodynamic stability of protein
      under pressure was discussed.

PMID- 11455592
TI  - Model of three-dimensional structure of vitamin D receptor and its binding
      mechanism with 1alpha,25-dihydroxyvitamin D(3).
AB  - Comparative modeling of the vitamin D receptor three-dimensional structure and
      computational docking of 1alpha,25-dihydroxyvitamin D(3) into the putative
      binding pocket of the two deletion mutant receptors: (207-423) and (120-422,
      Delta [164-207]) are reported and evaluated in the context of extensive mutagenic
      analysis and crystal structure of holo hVDR deletion protein published recently.
      The obtained molecular model agrees well with the experimentally determined
      structure. Six different conformers of 1alpha,25-dihydroxyvitamin D(3) were used
      to study flexible docking to the receptor. On the basis of values of
      conformational energy of various complexes and their consistency with functional
      activity, it appears that 1alpha,25-dihydroxyvitamin D(3) binds the receptor in
      its 6-s-trans form. The two lowest energy complexes obtained from docking the
      hormone into the deletion protein (207-423) differ in conformation of ring A and
      orientation of the ligand molecule in the VDR pocket. 1alpha,25-Dihydroxyvitamin
      D(3) possessing the A-ring conformation with axially oriented 1alpha-hydroxy
      group binds receptor with its 25-hydroxy substituent oriented toward the center
      of the receptor cavity, whereas ligand possessing equatorial conformation of
      1alpha-hydroxy enters the pocket with A ring directed inward. The latter
      conformation and orientation of the ligand is consistent with the crystal
      structure of hVDR deletion mutant (118-425, Delta [165-215]). The lattice model
      of rVDR (120-422, Delta [164-207]) shows excellent agreement with the crystal
      structure of the hVDR mutant. The complex obtained from docking the hormone into
      the receptor has lower energy than complexes for which homology modeling was
      used. Thus, a simple model of vitamin D receptor with the first two helices
      deleted can be potentially useful for designing a general structure of ligand,
      whereas the advanced lattice model is suitable for examining binding sites in the
      pocket.

PMID- 11455593
TI  - Solution structure and dynamics of ribonuclease Sa.
AB  - We have used NMR methods to characterize the structure and dynamics of
      ribonuclease Sa in solution. The solution structure of RNase Sa was obtained
      using the distance constraints provided by 2,276 NOEs and the C6-C96 disulfide
      bond. The 40 resulting structures are well determined; their mean pairwise RMSD
      is 0.76 A (backbone) and 1.26 A (heavy atoms). The solution structures are
      similar to previously determined crystal structures, especially in the secondary
      structure, but exhibit new features: the loop composed of Pro 45 to Ser 48 adopts
      distinct conformations and the rings of tyrosines 51, 52, and 55 have reduced
      flipping rates. Amide protons with greatly reduced exchange rates are found
      predominantly in interior beta-strands and the alpha-helix, but also in the
      external 3/10 helix and edge beta-strand linked by the disulfide bond. Analysis
      of (15)N relaxation experiments (R1, R2, and NOE) at 600 MHz revealed five
      segments, consisting of residues 1-5, 28-31, 46-50, 60-65, 74-77, retaining
      flexibility in solution. The change in conformation entropy for RNase SA folding
      is smaller than previously believed, since the native protein is more flexible in
      solution than in a crystal.

PMID- 11455594
TI  - Molecular engineering of a polymer of tetrameric hemoglobins.
AB  - We have engineered a recombinant mutant human hemoglobin, Hb Prisca
      beta(S9C+C93A+C112G), which assembles in a polymeric form. The polymerization is
      obtained through the formation of intermolecular S-S bonds between cysteine
      residues introduced at position beta9, on the model of Hb Porto Alegre (beta9Ser 
      -> Cys) (Bonaventura and Riggs, Science 1967;155:800-802). Cbeta93 and Cbeta112
      were replaced in order to prevent formation of spurious S&bond;S bonds during the
      expression, assembly, and polymerization events. Dynamic light scattering
      measurements indicate that the final polymerization product is mainly formed by 6
      to 8 tetrameric hemoglobin molecules. The sample polydispersity Q = 0.07 +/-
      0.02, is similar to that of purified human hemoglobin (Q = 0.02 +/- 0.02),
      consistent with a good degree of homogeneity. In the presence of strong reducing
      agents, the polymer reverts to its tetrameric form. During the depolymerization
      process, a direct correlation is observed between the hydrodynamic radius and the
      light scattering of the system, which, in turn, is proportional to the mass of
      the protein. We interpret this to indicate that the hemoglobin molecules are
      tightly packed in the polymer with no empty spaces. The tight packing of the
      hemoglobin molecules suggests that the polymer has a globular shape and, thus,
      allows estimation of its radius. An illustration of an arrangement of a finite
      number of tetrameric hemoglobin molecules is presented. The conformational and
      functional characteristics of this polymer, such as heme pocket conformation,
      stability to denaturation, autoxidation rate, oxygen affinity, and cooperativity,
      remain similar to those of tetrameric human hemoglobin.

PMID- 11455595
TI  - A distance-dependent atomic knowledge-based potential for improved protein
      structure selection.
AB  - A heavy atom distance-dependent knowledge-based pairwise potential has been
      developed. This statistical potential is first evaluated and optimized with the
      native structure z-scores from gapless threading. The potential is then used to
      recognize the native and near-native structures from both published decoy test
      sets, as well as decoys obtained from our group's protein structure prediction
      program. In the gapless threading test, there is an average z-score improvement
      of 4 units in the optimized atomic potential over the residue-based quasichemical
      potential. Examination of the z-scores for individual pairwise distance shells
      indicates that the specificity for the native protein structure is greatest at
      pairwise distances of 3.5-6.5 A, i.e., in the first solvation shell. On applying
      the current atomic potential to test sets obtained from the web, composed of
      native protein and decoy structures, the current generation of the potential
      performs better than residue-based potentials as well as the other published
      atomic potentials in the task of selecting native and near-native structures.
      This newly developed potential is also applied to structures of varying quality
      generated by our group's protein structure prediction program. The current atomic
      potential tends to pick lower RMSD structures than do residue-based contact
      potentials. In particular, this atomic pairwise interaction potential has better
      selectivity especially for near-native structures. As such, it can be used to
      select near-native folds generated by structure prediction algorithms as well as
      for protein structure refinement.

PMID- 11455596
TI  - Role of non-glycine residues in left-handed helical conformation for the
      conformational stability of human lysozyme.
AB  - To understand the role of non-Gly residues in the left-handed helical
      conformation for the conformational stability of a protein, the non-Gly to Gly
      and Ala mutations at six left-handed residues (R21, Y38, R50, Q58, H78, and N118)
      of the human lysozyme were examined. The thermodynamic parameters for
      denaturation were determined using a differential scanning calorimeter, and the
      crystal structures were analyzed by X-ray crystallography. If a left-handed non
      Gly had an unfavorable steric interaction between the side-chain Cbeta and
      backbone, the Gly mutation would be expected to stabilize more than the Ala
      mutation at the same position. For the mutant human lysozymes, however, there
      were few differences in the denaturation Gibbs energy (DeltaG) between the Gly
      and Ala mutants, except for the substitution at position 58. Analysis of the
      changes in stability (DeltaDeltaG) based on the structures of the wild-type and
      mutant proteins showed that the experimental DeltaDeltaG value of Q58G was
      approximately 7 kJ/mol higher than the estimated value without consideration of
      any local steric interaction. These results indicate that only Q58G increased the
      stability by elimination of local constraints. The residue 58 is located at the
      most rigid position in the left-handed non-Gly residues and is involved in its
      enzymatic function. It can be concluded that the left-handed non-Gly residues do
      not always have unfavorable strain energies as compared with Gly at the same
      position.

PMID- 11455597
TI  - Denatured collapsed states in protein folding: example of apomyoglobin.
AB  - Experimental approaches, including circular dichroism, small angle X-ray
      scattering, steady-state fluorescence, and fluorescence energy transfer, were
      applied to study the 3D-structure of apomyolgobin in different conformational
      states. These included the native and molten globules, along with either less
      ordered conformations induced by the addition of anions or completely unfolded
      states. The results show that the partially folded forms of apomyoglobin
      stabilized by KCl and/or Na(2)SO(4) under unfolding conditions (pH 2) exhibit a
      significant amount of secondary structure (circular dichroism), low packing
      density of protein molecules (SAXS), and native-like dimensions of the AGH core
      (fluorescence energy transfer). This finding indicates that a native-like
      tertiary fold of the polypeptide chain, i.e., the spatial organization of
      secondary structure elements, most likely emerges prior to the formation of the
      molten globule state.

PMID- 11455598
TI  - Binding of AMP to two of the four subunits of pig kidney fructose-1,6
      bisphosphatase induces the allosteric transition.
AB  - To study the allosteric transition in pig kidney fructose 1,6-bisphosphatase
      (FBPase), we constructed hybrids in which subunits have either their active or
      regulatory sites rendered nonfunctional by specific mutations. This was
      accomplished by the coexpression of the enzyme from a plasmid that contained two
      slightly different copies of the cDNA. To resolve and purify each of the hybrid
      enzymes, six aspartic acid codons were added before the termination codon of one
      of the cDNAs. The addition of these Asp residues to the protein did not alter the
      kinetic or allosteric properties of the resulting FBPase. Expression of the
      enzyme from a dual-gene plasmid resulted in the production of a set of five
      different enzymes (two homotetramers and three hybrid tetramers) that could be
      purified by a combination of affinity and anion-exchange chromatography because
      of the differential charge on each of these species. The hybrid with one subunit
      that only had a functional regulatory site (R) and three subunits that only had a
      functional active site (A) exhibited biphasic AMP inhibition. Analysis of these
      data suggest that the binding of AMP to the R subunit is able to globally alter
      the activity of the other three A subunits. The hybrid composed of two R and two
      A subunits is completely inhibited at an AMP concentration of approximately 0.5
      mM, 100-fold less than the concentration required to fully inhibit the A(4)
      enzyme. The monophasic nature of this cooperative inhibition suggests that the
      AMP binding to the two R subunits is sufficient to completely inhibit the enzyme
      and suggests that the binding of AMP to only two of the four subunits of the
      enzyme induces the global allosteric transition from the R to the T state.

PMID- 11455599
TI  - Role of the carboxy-termini of tubulin on its chaperone-like activity.
AB  - Mutational analysis and the enzymatic digestion of many chaperones indicate the
      importance of both hydrophobic and hydrophilic residues for their unique
      property. Thus, the chaperone activity of alpha-crystallin is lost due to the
      substitution of hydrophobic residues or upon enzymatic digestion of the
      negatively charged residues. Tubulin, an eukaryotic cytoskeletal protein,
      exhibits chaperone-like activity as demonstrated by prevention of DTT-induced
      aggregation of insulin, thermal aggregation of alcohol dehydrogenase, betagamma
      crystallin, and other proteins. We have shown that the tubulin lost its chaperone
      like activity upon digestion of its negatively charged C-termini. In this
      article, the role of the C-terminus of individual subunits has been investigated.
      We observe that the digestion of C-terminus of beta-subunit with subtilisin
      causes loss of chaperone-like activity of tubulin. The contribution of C-terminus
      of alpha-subunit is difficult to establish directly as subtilisin cleaves C
      terminus of beta-subunit first. This has been ascertained indirectly using a 14
      residue peptide P2 having the sequence corresponding to a conserved region of MHC
      class I molecules and that binds tightly to the C-terminus of alpha-subunit. We
      have shown that the binding of P2 peptide to alphabeta-tubulin causes complete
      loss of its chaperone-like activity. NMR and gel-electrophoresis studies indicate
      that the P2 peptide has a significant higher binding affinity for the C-terminus
      of alpha-subunit compared to that of beta-subunit. Thus, we conclude that both
      the C-termini are necessary for the chaperone-like activity of tubulin.
      Implications for the chaperone functions in vivo have been discussed.

PMID- 11455600
TI  - Substrate flow in catalases deduced from the crystal structures of active site
      variants of HPII from Escherichia coli.
AB  - The active site of heme catalases is buried deep inside a structurally highly
      conserved homotetramer. Channels leading to the active site have been identified
      as potential routes for substrate flow and product release, although evidence in
      support of this model is limited. To investigate further the role of protein
      structure and molecular channels in catalysis, the crystal structures of four
      active site variants of catalase HPII from Escherichia coli (His128Ala,
      His128Asn, Asn201Ala, and Asn201His) have been determined at approximately 2.0-A
      resolution. The solvent organization shows major rearrangements with respect to
      native HPII, not only in the vicinity of the replaced residues but also in the
      main molecular channel leading to the heme distal pocket. In the two inactive
      His128 variants, continuous chains of hydrogen bonded water molecules extend from
      the molecular surface to the heme distal pocket filling the main channel. The
      differences in continuity of solvent molecules between the native and variant
      structures illustrate how sensitive the solvent matrix is to subtle changes in
      structure. It is hypothesized that the slightly larger H(2)O(2) passing through
      the channel of the native enzyme will promote the formation of a continuous chain
      of solvent and peroxide. The structure of the His128Asn variant complexed with
      hydrogen peroxide has also been determined at 2.3-A resolution, revealing the
      existence of hydrogen peroxide binding sites both in the heme distal pocket and
      in the main channel. Unexpectedly, the largest changes in protein structure
      resulting from peroxide binding are clustered on the heme proximal side and
      mainly involve residues in only two subunits, leading to a departure from the 222
      point group symmetry of the native enzyme. An active role for channels in the
      selective flow of substrates through the catalase molecule is proposed as an
      integral feature of the catalytic mechanism. The Asn201His variant of HPII was
      found to contain unoxidized heme b in combination with the proximal side His-Tyr
      bond suggesting that the mechanistic pathways of the two reactions can be
      uncoupled.

PMID- 11455601
TI  - Adenine recognition: a motif present in ATP-, CoA-, NAD-, NADP-, and FAD
      dependent proteins.
AB  - Adenosine triphosphate (ATP) plays an essential role in energy transfer within
      the cell. In the form of NAD, adenine participates in multiple redox reactions.
      Phosphorylation and ATP-hydrolysis reactions have key roles in signal
      transduction and regulation of many proteins, especially enzymes. In each cell,
      proteins with many different functions use adenine and its derivatives as
      ligands; adenine, of course, is present in DNA and RNA. We show that an adenine
      binding motif, which differs according to the backbone chain direction of a loop
      that binds adenine (and in one variant by the participation of an aspartate side
      chain), is common to many proteins; it was found from an analysis of all
      adenylate-containing protein structures from the Protein Data Bank. Indeed, 224
      protein-ligand complexes (86 different proteins) from a total of 645 protein
      structure files bind ATP, CoA, NAD, NADP, FAD, or other adenine-containing
      ligands, and use the same structural elements to recognize adenine, regardless of
      whether the ligand is a coenzyme, cofactor, substrate, or an allosteric effector.
      The common adenine-binding motif shown in this study is simple to construct. It
      uses only (1) backbone polar interactions that are not dependent on the protein
      sequence or particular properties of amino acid side-chains, and (2) nonspecific
      hydrophobic interactions. This is probably why so many different proteins with
      different functions use this motif to bind an adenylate-containing ligand. The
      adenylate-binding motif reported is present in "ancient proteins" common to all
      living organisms, suggesting that adenine-containing ligands and the common motif
      for binding them were exploited very early in evolution. The geometry of adenine
      binding by this motif mimics almost exactly the geometry of adenine base-pairing
      seen in DNA and RNA.

PMID- 11455602
TI  - Elucidating protein secondary structures using alpha-carbon recurrence
      quantifications.
AB  - Secondary structures of proteins were studied by recurrence quantification
      analysis (RQA). High-resolution, 3-dimensional coordinates of alpha-carbon atoms
      comprising a set of 68 proteins were downloaded from the Protein Data Bank. By
      fine-tuning four recurrence parameters (radius, line, residue, separation), it
      was possible to establish excellent agreement between percent contribution of
      alpha-helix and beta-sheet structures determined independently by RQA and that of
      the DSSP algorithm (Define Secondary Structure of Proteins). These results
      indicate that there is an equivalency between these two techniques, which are
      based upon totally different pattern recognition strategies. RQA enhances
      qualitative contact maps by quantifying the arrangements of recurrent points of
      alpha carbons close in 3-dimensional space. For example, the radius was
      systematically increased, moving the analysis beyond local alpha-carbon
      neighborhoods in order to capture super-secondary and tertiary structures.
      However, differences between proteins could only be detected within distances up
      to about 6-11 A, but not higher. This result underscores the complexity of alpha
      carbon spacing when super-secondary structures appear at larger distances.
      Finally, RQA-defined secondary structures were found to be robust against random
      displacement of alpha carbons upwards of 1 A. This finding has potential import
      for the dynamic functions of proteins in motion.

PMID- 11455603
TI  - The crystal structure of chorismate lyase shows a new fold and a tightly retained
      product.
AB  - The enzyme chorismate lyase (CL) catalyzes the removal of pyruvate from
      chorismate to produce 4-hydroxy benzoate (4HB) for the ubiquinone pathway. In
      Escherichia coli, CL is monomeric, with 164 residues. We have determined the
      structure of the CL product complex by crystallographic heavy-atom methods and
      report the structure at 1.4-A resolution for a fully active double Cys-to-Ser
      mutant and at 2.0-A resolution for the wild-type. The fold involves a 6-stranded
      antiparallel beta-sheet with no spanning helices and novel connectivity. The
      product is bound internally, adjacent to the sheet, with its polar groups
      coordinated by two main-chain amides and by the buried side-chains of Arg 76 and
      Glu 155. The 4HB is completely sequestered from solvent in a largely hydrophobic
      environment behind two helix-turn-helix loops. The extensive product binding that
      is observed is consistent with biochemical measurements of slow product release
      and 10-fold stronger binding of product than substrate. Substrate binding and
      kinetically rate-limiting product release apparently require the rearrangement of
      these active-site-covering loops. Implications for the biological function of the
      high product binding are considered in light of the unique cellular role of 4HB,
      which is produced by cytoplasmic CL but is used by the membrane-bound enzyme 4HB
      octaprenyltransferase.

PMID- 11455604
TI  - Model for the three-dimensional structure of vitronectin: predictions for the
      multi-domain protein from threading and docking.
AB  - The structure of vitronectin, an adhesive protein that circulates in high
      concentrations in human plasma, was predicted through a combination of
      computational methods and experimental approaches. Fold recognition and sequence
      structure alignment were performed using the threading program PROSPECT for each
      of three structural domains, i.e., the N-terminal somatomedin B domain (residues
      1-53), the central region that folds into a four-bladed beta-propeller domain
      (residues 131-342), and the C-terminal heparin-binding domain (residues 347-459).
      The atomic structure of each domain was generated using MODELLER, based on the
      alignment obtained from threading. Docking experiments between the central and C
      terminal domains were conducted using the program GRAMM, with limits on the
      degrees of freedom from a known inter-domain disulfide bridge. The docked
      structure has a large inter-domain contact surface and defines a putative heparin
      binding groove at the inter-domain interface. We also docked heparin together
      with the combined structure of the central and C-terminal domains, using GRAMM.
      The predictions from the threading and docking experiments are consistent with
      experimental data on purified plasma vitronectin pertaining to protease
      sensitivity, ligand-binding sites, and buried cysteines.

PMID- 11455605
TI  - Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness
      shared by cysteine-rich motifs.
AB  - This report describes the application of a simple computational tool, AAPAIR.TAB,
      for the systematic analysis of the cysteine-rich EGF, Sushi, and Laminin
      motif/sequence families at the two-amino acid level. Automated dipeptide
      frequency/bias analysis detects preferences in the distribution of amino acids in
      established protein families, by determining which "ordered dipeptides" occur
      most frequently in comprehensive motif-specific sequence data sets. Graphic
      display of the dipeptide frequency/bias data revealed family-specific preferences
      for certain dipeptides, but more importantly detected a shared preference for
      employment of the ordered dipeptides Gly-Tyr (GY) and Gly-Phe (GF) in all three
      protein families. The dipeptide Asn-Gly (NG) also exhibited high-frequency and
      bias in the EGF and Sushi motif families, whereas Asn-Thr (NT) was distinguished
      in the Laminin family. Evaluation of the distribution of dipeptides identified by
      frequency/bias analysis subsequently revealed the highly restricted localization
      of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme
      conservation in the consensus sequence of all three sequence families. The
      similar employment of the high-frequency/bias dipeptides in three distinct
      protein sequence families was further correlated with the concurrence of these
      shared molecular determinants at similar positions within the distinctive
      scaffolds of three structurally divergent, but similarly employed, motif modules.

PMID- 11455606
TI  - Protochlorophyllide oxidoreductase: a homology model examined by site-directed
      mutagenesis.
AB  - An homology model of protochlorophyllide reductase (POR) from Synechocystis sp.
      was constructed on a template from the tyrosine-dependent oxidoreductase family.
      The model showed characteristics appropriate to a globular, soluble protein and
      was used to generate a structure of the ternary complex of POR, nicotinamide
      adenine dinucleotide phosphate (NADPH), and protochlorophyllide. The POR ternary
      model was validated by mutagenesis experiments involving predicted coenzyme
      binding residues and by chemical modification experiments. A core tryptophan
      residue was shown to be responsible for much of the protein's fluorescence. Both
      quenching of this residue by coenzyme and fluorescence resonance energy transfer
      (FRET) from the protein to the coenzyme allowed the binding constant of NADPH to
      be determined. Replacement of this residue by Tyr gave an active mutant with
      approximately halved fluorescence and a negligible FRET signal, consistent with
      the role of this residue in energy transfer to the NADPH at the active site and
      with the model. The mechanism of the enzyme is discussed in the context of the
      model and semiempirical molecular orbital calculations.

PMID- 11455607
TI  - Prediction of protein interaction sites from sequence profile and residue
      neighbor list.
AB  - Protein-protein interaction sites are predicted from a neural network with
      sequence profiles of neighboring residues and solvent exposure as input. The
      network was trained on 615 pairs of nonhomologous complex-forming proteins.
      Tested on a different set of 129 pairs of nonhomologous complex-forming proteins,
      70% of the 11,004 predicted interface residues are actually located in the
      interfaces. These 7732 correctly predicted residues account for 65% of the 11,805
      residues making up the 129 interfaces. The main strength of the network predictor
      lies in the fact that neighbor lists and solvent exposure are relatively
      insensitive to structural changes accompanying complex formation. As such, it
      performs equally well with bound or unbound structures of the proteins. For a set
      of 35 test proteins, when the input was calculated from the bound and unbound
      structures, the correct fractions of the predicted interface residues were 69 and
      70%, respectively.

PMID- 11455608
TI  - alpha-helix formation: discontinuous molecular dynamics on an intermediate
      resolution protein model.
AB  - An intermediate-resolution model of small, homogeneous peptides is introduced,
      and discontinuous molecular dynamics simulation is applied to study secondary
      structure formation. Physically, each model residue consists of a detailed three
      bead backbone and a simplified single-bead side-chain. Excluded volume and
      hydrogen bond interactions are constructed with discontinuous (i.e., hard-sphere
      and square-well) potentials. Simulation results show that the backbone motion of
      the model is limited to realistic regions of Phi-Psi conformational space. Model
      polyalanine chains undergo a locally cooperative transition to form alpha-helices
      that are stabilized by backbone hydrogen bonding, while model polyglycine chains
      tend to adopt nonhelical structures. When side-chain size is increased beyond a
      critical diameter, steric interactions prevent formation of long alpha-helices.
      These trends in helicity as a function of residue type have been well documented
      by experimental, theoretical, and simulation studies and demonstrate the ability
      of the intermediate-resolution model developed in this work to accurately mimic
      realistic peptide behavior. The efficient algorithm used permits observation of
      the complete helix-coil transition within 15 min on a single-processor
      workstation, suggesting that simulations of very long times are possible with
      this model.

PMID- 11455609
TI  - PRED-CLASS: cascading neural networks for generalized protein classification and
      genome-wide applications.
AB  - A cascading system of hierarchical, artificial neural networks (named PRED-CLASS)
      is presented for the generalized classification of proteins into four distinct
      classes-transmembrane, fibrous, globular, and mixed-from information solely
      encoded in their amino acid sequences. The architecture of the individual
      component networks is kept very simple, reducing the number of free parameters
      (network synaptic weights) for faster training, improved generalization, and the
      avoidance of data overfitting. Capturing information from as few as 50 protein
      sequences spread among the four target classes (6 transmembrane, 10 fibrous, 13
      globular, and 17 mixed), PRED-CLASS was able to obtain 371 correct predictions
      out of a set of 387 proteins (success rate approximately 96%) unambiguously
      assigned into one of the target classes. The application of PRED-CLASS to several
      test sets and complete proteomes of several organisms demonstrates that such a
      method could serve as a valuable tool in the annotation of genomic open reading
      frames with no functional assignment or as a preliminary step in fold recognition
      and ab initio structure prediction methods. Detailed results obtained for various
      data sets and completed genomes, along with a web sever running the PRED-CLASS
      algorithm, can be accessed over the World Wide Web at http://o2.biol.uoa.gr/PRED
      CLASS.

PMID- 11455610
TI  - A new method to model membrane protein structure based on silent amino acid
      substitutions.
AB  - The importance of accurately modeling membrane proteins cannot be overstated, in
      lieu of the difficulties in solving their structures experimentally. Often,
      however, modeling procedures (e.g., global searching molecular dynamics) generate
      several possible candidates rather then pointing to a single model. Herein we
      present a new approach to select among candidate models based on the general
      hypothesis that silent amino acid substitutions, present in variants identified
      from evolutionary conservation data or mutagenesis analysis, do not affect the
      stability of a native structure but may destabilize the non-native structures
      also found. The proof of this hypothesis has been tested on the alpha-helical
      transmembrane domains of two homodimers, human glycophorin A and human CD3-zeta,
      a component of the T-cell receptor. For both proteins, only one structure was
      identified using all the variants. For glycophorin A, this structure is virtually
      identical to the structure determined experimentally by NMR. We present a model
      for the transmembrane domain of CD3-zeta that is consistent with predictions
      based on mutagenesis, homology modeling, and the presence of a disulfide bond.
      Our experiments suggest that this method allows the prediction of transmembrane
      domain structure based only on widely available evolutionary conservation data.

PMID- 11455611
TI  - Assembly of a tetrameric alpha-helical bundle: computer simulations on an
      intermediate-resolution protein model.
AB  - Discontinuous molecular dynamics (DMD) simulation on an intermediate-resolution
      protein model is used to study the folding of an isolated, small model peptide to
      an amphipathic alpha-helix and the assembly of four of these model peptides into
      a four-helix bundle. A total of 129 simulations were performed on the isolated
      peptide, and 50 simulations were performed on the four-peptide system.
      Simulations efficiently sample conformational space allowing complete folding
      trajectories from random initial configurations to be observed within 15 min for
      the one-peptide system and within 15 h for the four-peptide system on a 500-MHz
      workstation. The native structures of both the alpha-helix and the four-helix
      bundle are consistent with experimental characterization studies and with results
      from previous simulations on these model peptides. In both the one- and four
      peptide systems, the native state is achieved during simulations within an
      optimal temperature range, a phenomenon also observed experimentally. The ease
      with which our simulations yield reasonable estimates of folded structures
      demonstrates the power of the intermediate-resolution model developed for this
      work and the DMD algorithm and suggests that simulations of very long times and
      of multiprotein systems may be possible with this model.

PMID- 11455612
TI  - Self-repair of biological fibers catalyzed by the surface of a virus crystal.
AB  - Helical fibers, presumably proteinaceous and of microbial origin, have been
      visualized by atomic force microscopy on the surfaces of crystals of satellite
      tobacco mosaic virus. If the crystals are growing, then the fibers are
      incorporated intact into the crystal lattice. If broken on the crystal surface,
      then within a few minutes, the fibers self-reassemble to reestablish continuity.
      This, we believe, is the first observation of such a crystal surface-catalyzed
      repair of a biological structure. The surfaces of virus crystals provide ideal
      workbenches for the visualization and manipulation of nanoscale objects,
      particularly extended structures such as these fibers.

PMID- 11455613
TI  - Microglial interaction with beta-amyloid: implications for the pathogenesis of
      Alzheimer's disease.
AB  - The etiology of Alzheimer's disease (AD) involves a significant inflammatory
      component as evidenced by the presence of elevated levels of a diverse range of
      proinflammatory molecules in the AD brain. These inflammatory molecules are
      produced principally by activated microglia, which are found to be clustered
      within and adjacent to the senile plaque. Moreover, long-term treatment of
      patients with non-steroidal anti-inflammatory drugs has been shown to reduce risk
      and incidence of AD and delay disease progression. The microglia respond to beta
      amyloid (Abeta) deposition in the brain through the interaction of fibrillar
      forms of amyloid with cell surface receptors, leading to the activation of
      intracellular signal transduction cascades. The activation of multiple
      independent signaling pathways ultimately leads to the induction of
      proinflammatory gene expression and production of reactive oxygen and nitrogen
      species. These microglial inflammatory products act in concert to produce
      neuronal toxicity and death. Therapeutic approaches focused on inhibition of the
      microglial-mediated local inflammatory response in the AD brain offer new
      opportunities to intervene in the disease.

PMID- 11455614
TI  - Microglia and prion disease.
AB  - Gliosis is one of the hallmarks of the prion diseases. Prion diseases are fatal
      neurodegenerative conditions of low incidence made famous by both the hypothesis
      that a protein acts as the infectious agent without involvement of nucleic acid
      and the speculative idea that a disease of cattle, BSE, has spread to humans from
      the ingestion of prion-infected beef. Despite these unproved hypotheses, the
      aetiology of the prion diseases remains unsolved. The rapid degenerative course
      of the disease is preceded by a long incubation period with little or no
      symptoms. The rapid neurodegeneration in the disease follows from increased
      deposition of an abnormal isoform of a normal neuronal protein. Co-incident with
      the appearance of this abnormal protein is the activation of large numbers of
      microglia. Studies in cell culture with both the abnormal prion protein and a
      peptide-mimic suggest that neuronal degeneration occurs because of two concurrent
      effects. First, there is a reduction in neuronal resistance to toxic insults and,
      second, there is an increase in the production of toxic substances such as
      reactive oxygen species by microglia and a decrease in glutamate clearance by
      astrocytes. Microglia activated by the abnormal form of the prion protein also
      release cytokines, which stimulate changes in astrocytes such as proliferation.
      The implication of this is that microglia may play a major role in initiating the
      pathological changes in prion disease. This review discusses the role of
      microglia in these changes.

PMID- 11455615
TI  - Phagocytic properties of microglia in vitro: implications for a role in multiple
      sclerosis and EAE.
AB  - The microglial cell, after many years of neglect, has become recognized as the
      sole representative cell of the immune system that resides in the normal central
      nervous system. While normally dormant, microglia can be activated by secretory
      substances or signals associated with disease or injury, and becomes a phagocytic
      cell, which also produces its own injurious molecules. In the activating process,
      its morphology is changed from a resting process-bearing cell, into a rounded
      amoebic form, and displays new or increased amounts of functional markers, such
      as receptors and Class I and Class II MHC molecules. Microglia prepared from
      newborn mice or rats for tissue culture are already activated, and can be used
      for studies of their phagocytic properties. Although they can phagocytize foreign
      substances, their uptake and metabolism of myelin are emphasized here, in keeping
      with their role in demyelinating diseases. A number of receptors have been
      implicated and appear to be important in the attachment to, and ingestion of,
      myelin particles in vitro, including the Fc, complement, macrophage scavenger,
      and the Galectin-3/MAC-2 receptors, although the alpha2-macroglobulin/low-density
      lipoprotein receptor and mannose receptors have also been suggested as
      participants in myelin phagocytosis. Certain cytokines and adhesion molecules
      also regulate the phagocytic activity of microglia. Comparative in vitro studies
      of phagocytosis by peritoneal macrophages and microglia have shown that the two
      kinds of cells respond differently to regulatory molecules, and it is concluded
      that they have different innate properties. The role of microglia in the
      demyelinative diseases experimental autoimmune encephalomyelitis and multiple
      sclerosis is emphasized here, and the possible means of intervention in the
      process leading to myelin destruction is discussed. Published 2001 Wiley-Liss,
      Inc.

PMID- 11455616
TI  - Microglia in HIV-associated neurological diseases.
AB  - Human immunodeficiency virus type-1 (HIV-1) is a neurotropic virus linked to a
      variety of progressive neurologic disorders. This review describes our current
      understanding of how HIV-1 enters the nervous system and interacts with neuronal
      and non-neuronal cells to initiate and sustain neurologic dysfunction. The
      overwhelming majority of cells infected with HIV-1 in the nervous system are
      microglia/macrophages. Microglial/macrophage infection leads to immune
      dysregulation as well as production and release of cytotoxic molecules.
      Interaction of these infected cells with astrocytes may accelerate neurotoxic
      mechanisms. A hypothetical scenario for how HIV-1 infection leads to neurologic
      disease is presented.

PMID- 11455617
TI  - Role of microglia in glioma biology.
AB  - Microglia, a type of differentiated tissue macrophage, are considered to be the
      most plastic cell population of the central nervous system (CNS). In response to
      pathological conditions, resting microglia undergo a stereotypic activation
      process and become capable of phagocytosis, antigen presentation, and lymphocyte
      activation. Considering their immune effector function, it is not surprising to
      see microglia accumulation in almost every CNS disease process, including
      malignant brain tumors or malignant gliomas. Although the function of these cells
      in CNS inflammatory processes is being studied, their role in malignant glioma
      biology remains unclear. On one hand, microglia may represent a CNS anti-tumor
      response, which is inactivated by local secretion of immunosuppressive factors by
      glioma cells. On the other hand, taking into account that microglia are capable
      of secreting a variety of immunomodulatory cytokines, it is possible that they
      are attracted by gliomas to promote tumor growth. A better understanding of
      microglia-glioma interaction will be helpful in designing novel immune-based
      therapies against these fatal tumors.

PMID- 11455618
TI  - Multiple connexins localized to individual gap-junctional plaques in human
      myometrial smooth muscle.
AB  - The synchronous contractions of the uterus in labour depend on electrical
      coupling of myometrial smooth muscle cells by gap junctions. In the human
      myometrium, gap junctions are scarce in the non-pregnant uterus, but become
      abundant at term in preparation for labour. We have previously demonstrated that
      in the human myometrium at term, three different gap-junctional proteins are
      expressed, connexins 43, 45, and 40. These connexins are known to have
      distinctive functional capacities in in vitro expression systems but whether, in
      the human myometrium in vivo, they are co-assembled into the same gap junction or
      form different types of gap junction has previously been unclear. By applying
      triple immunogold labelling to sections of Lowicryl-embedded tissue for electron
      microscopy, together with complementary immunoconfocal microscopy, we demonstrate
      here that connexins 43, 45, and 40 are commonly present as mixtures within the
      same gap-junctional plaque. While all gap junctions contain connexin43, the
      relative signal for each connexin type varies between individual junctions. The
      presence within single gap-junctional plaques of three different connexins, each
      with the potential for conferring distinctive channel properties, suggests an
      inherent versatility for modulation of smooth muscle cell intercellular
      communication properties during human parturition.

PMID- 11455627
TI  - Effects of temperature and concentration of the accelerators ethoxylated
      alcohols, diethyl suberate and tributyl phosphate on the mobility of [14C]2,4
      dichlorophenoxy butyric acid in plant cuticles.
AB  - Intrinsic activities of monodisperse ethoxylated dodecanols (MEDs), diethyl
      suberate (DESU) and tributyl phosphate (TBP) were investigated using Stephanotis
      floribunda leaf cuticular membranes (CMs) and [14C]2,4-dichlorophenoxy butyric
      acid (2,4-DB) as a model solute. When sorbed in cuticular membranes, MEDs, DESU
      and TBP increase solute mobility and are called accelerators for this reason.
      With MEDs, dose-effect curves (log mobility vs accelerator concentration) were
      linear but, with DESU and TBP, curves convex to the x axes were obtained that
      approached a maximum at 90 and 150 g kg-1, respectively. Accelerators increased
      the mobility of 2,4-DB in the CMs by 9- to 48-fold, and effects were larger at
      lower temperatures (range 15-30 degrees C). Activation energy for diffusion of
      2,4-DB was 105 kJ mol-1, decreasing with increasing accelerator concentrations to
      26 kJ mol-1 with DESU at 90 g kg-1 and 64 kJ mol-1 with TBP at 150 g kg-1. Thus,
      the intrinsic activity of DESU was much higher than that of TBP, which implies
      that, for a given effect, less DESU than TBP would be needed. MEDs were also very
      effective accelerators, lowering activation energies to 36 kJ mol-1. Data are
      discussed in relation to increasing rates of foliar penetration of active
      ingredients at low temperatures.

PMID- 11455628
TI  - Insecticidal activity of glufosinate through glutamine depletion in a
      caterpillar.
AB  - The herbicide glufosinate-ammonium (GLA) is a competitive inhibitor of glutamine
      synthetase (GS), an enzyme converting glutamate to glutamine in both plants and
      animals. Because GS is essential for ammonia detoxification in plants, GLA
      treatment disrupts photorespiration by causing a build-up of ammonia and a loss
      of glutamine in plant tissues. This study reports that GLA applied to leaf
      surfaces is also toxic to 5th-instar caterpillars of the skipper butterfly
      Calpodes ethlius (LD50 = 400 mg kg-1). After ingesting GLA, caterpillars stopped
      feeding and became dehydrated through a loss of rectal function. Caterpillars
      showed symptoms of neurotoxicity, such as proleg tremors, body convulsions and
      complete paralysis before death. Incubation of several tissues isolated from
      normal feeding-stage caterpillars with the GS substrates glutamate and ammonium
      showed that GLA inhibited GS activity in vitro. Within 24 h of ingesting GLA,
      caterpillars had a greatly reduced glutamine content and the ammonium ion levels
      had more than doubled. Injection of ammonium chloride into non-GLA-treated
      caterpillars had no deleterious effect, suggesting that glutamine depletion, and
      not a rise in body ammonium, was the primary cause of GLA toxicity following GS
      inhibition. This was supported by the observation that the onset of the symptoms
      of GLA poisoning could be postponed by giving GLA-fed caterpillars several
      subsequent daily injections of glutamine. The effective GLA dose fed to 5th
      instar caterpillars in this study was comparable to the amount that might
      realistically by acquired from feeding on GLA-treated crops.

PMID- 11455629
TI  - Selecting the right compounds for screening: does Lipinski's Rule of 5 for
      pharmaceuticals apply to agrochemicals?
AB  - Large numbers of compounds are now available through combinatorial chemistry and
      from compound vendors to screen for lead-level agrochemical activity. The
      likelihood that compounds with whole-organism activity will be discovered can be
      increased if compounds with physicochemical parameters consistent with transport
      to the target site are selected for screening. Certain ranges of simple
      parameters (molecular mass, log P, hydrogen-bond donors and acceptors, rotatable
      bonds) have been correlated with oral bioavailability of drugs. The distribution
      of these parameters for commercial insecticides and post-emergence herbicides was
      examined and ranges consistent with whole-organism activity are proposed for the
      two classes of agrochemical. The most significant difference identified between
      drugs and these two classes of agrochemicals was the lower numbers of hydrogen
      bond donors allowed in the latter cases. The frequency with which certain
      functional groups occur in drugs and agrochemicals was also compared.

PMID- 11455630
TI  - Mode of bleaching phytotoxicity of herbicidal diphenylpyrrolidinones.
AB  - A mode of action study of herbicidal diphenylpyrrolidinones was carried out
      through carotenoid analyses in intact Scenedesmus cells and by a cell-free plant
      type phytoene desaturase assay using Escherichia coli transformants. A series of
      forty-eight diphenylpyrrolidinones decreased the carotenoid content of
      Scenedesmus cells in the light and inhibited phytoene desaturase. The
      relationship between substituents at various positions and inhibition of phytoene
      desaturase is discussed. Using very active bleaching diphenylpyrrolidinones, a
      10(-5) M concentration affected neither the zeta-carotene desaturase nor the
      protoporphyrinogen-IX oxidase. Although some differences in their inhibitory
      activity were found between the in vivo and cell-free assays, it is concluded
      that the compounds are essentially bleachers affecting carotenoid biosynthesis in
      plants. Enzyme kinetics studies with recombinant phytoene desaturase revealed a
      non-competitive inhibition with respect to the substrate phytoene. A competition
      against the inhibitor was shown by the cofactor NADP+, suggesting an interaction
      of pyrrolidinones at the cofactor-binding site of phytoene desaturase.

PMID- 11455631
TI  - Laboratory evaluation of fipronil, a phenylpyrazole insecticide, against adult
      Anopheles (Diptera: Culicidae) and investigation of its possible cross-resistance
      with dieldrin in Anopheles stephensi.
AB  - Adult mosquitoes from two strains of Anopheles gambiae and from three strains of
      Anopheles stephensi were exposed to 0.25% fipronil-treated papers in WHO test
      kits or to 500 mg fipronil m-2 impregnated mosquito netting in bioassay spheres.
      For comparison, tests were also carried out with the pyrethroid permethrin, using
      the same methods and doses, and on papers treated with 0.4 and 4% of the
      cyclodiene insecticide dieldrin. Compared with the same doses of permethrin,
      fipronil showed less and delayed activity. Two of the An stephensi strains were
      resistant to fipronil and dieldrin. To investigate whether this was due to a
      resistance mechanism in the An stephensi strains acting against both
      insecticides, the most fipronil- and dieldrin-tolerant strain was further
      selected in two separate lines with one of the insecticides, followed by tests
      with the insecticide that the line had not been selected with. This indicated a
      concomitant rise of resistance to dieldrin in the fipronil-selected line and vice
      versa. Repeated back-crossing of the two lines with a susceptible strain and re
      selection with either dieldrin or fipronil gave evidence for the involvement of a
      single resistance mechanisms to both insecticides. Permethrin resistance in both
      lines declined with selection for dieldrin or fipronil and confirms the absence
      of cross-resistance between fipronil and pyrethroids.

PMID- 11455632
TI  - Metabolism of the herbicide glufosinate-ammonium in plant cell cultures of
      transgenic (rhizomania-resistant) and non-transgenic sugarbeet (Beta vulgaris),
      carrot (Daucus carota), purple foxglove (Digitalis purpurea) and thorn apple
      (Datura stramonium).
AB  - The metabolism of the herbicide glufosinate-ammonium was investigated in
      heterotrophic cell suspension and callus cultures of transgenic (bar-gene) and
      non-transgenic sugarbeet (Beta vulgaris). Similar studies were performed with
      suspensions of carrot (Daucus carota), purple foxglove (Digitalis purpurea) and
      thorn apple (Datura stramonium). 14C-labelled chemicals were the (racemic)
      glufosinate, L-glufosinate, and D-glufosinate, as well as the metabolites N
      acetyl L-glufosinate and 3-(hydroxymethylphosphinyl)propionic acid (MPP).
      Cellular absorption was generally low, but depended noticeably on plant species,
      substance and enantiomer. Portions of non-extractable residues ranged from 0.1%
      to 1.2% of applied 14C. Amounts of soluble metabolites resulting from glufosinate
      or L-glufosinate were between 0.0% and 26.7% of absorbed 14C in non-transgenic
      cultures and 28.2% and 59.9% in transgenic sugarbeet. D-Glufosinate, MPP and N
      acetyl L-glufosinate proved to be stable. The main metabolite in transgenic
      sugarbeet was N-acetyl L-glufosinate, besides traces of MPP and 4
      (hydroxymethylphosphinyl)butanoic acid (MPB). In non-transgenic sugarbeet,
      glufosinate was transformed to a limited extent to MPP and trace amounts of MPB.
      In carrot, D stramonium and D purpurea, MPP was also the main product; MPB was
      identified as a further trace metabolite in D stramonium and D purpurea.

PMID- 11455633
TI  - Effect of dietary cowpea trypsin inhibitor (CpTI) on the growth and development
      of the tomato moth Lacanobia oleracea (Lepidoptera: Noctuidae) and on the success
      of the gregarious ectoparasitoid Eulophus pennicornis (Hymenoptera: Eulophidae).
AB  - Cowpea trypsin inhibitor (CpTI) was shown to have a deleterious effect on the
      growth and development of larvae of the tomato moth, Lacanobia oleracea, when
      incorporated in artificial diet (2.0% of soluble protein) and expressed in
      transgenic potato leaf (up to 1.0% of soluble protein). The effect of CpTI on
      parasitism of L oleracea by the ectoparasitoid Eulophus pennicornis was
      investigated. The parasitic success of the wasp was reduced by the presence of
      CpTI in the diet of the host and, in the case of transgenic potato leaves
      expressing the transgene protein, was collated with the length of time the host
      fed on the diet prior to parasitism. In all cases the proportion of hosts
      parasitised when fed CpTI-containing diets was reduced when compared with
      controls, although these differences were only significant when hosts were fed
      from the third instar on the transgenic potato leaves. Parasitoid progeny that
      developed on L oleracea reared on CpTI-containing diets, however, were not
      adversely affected. These results show that, whilst expression of CpTI in
      transgenic potato plants confers resistance to the lepidopterous pest L oleracea,
      adverse effects on the ability of the ectoparasitoid E pennicornis to parasitise
      this moth species successfully may also occur. These results are discussed in
      relation to the potential impact of transgenic crops on beneficial biological
      control agents.

PMID- 11455634
TI  - DNA hybridization assay for detection of nucleopolyhedrovirus in whitemarked
      tussock moth (Orgyia leucostigma) larvae.
AB  - DNA dot-blot hybridization assays utilizing a horseradish peroxidase-labelled
      whole genomic DNA probe and enhanced chemiluminescence were conducted to quantify
      detection thresholds of nucleopolyhedrovirus (NPV) in whitemarked tussock moth
      (Orgyia leucostigma) larvae. The minimum detection thresholds for an aqueous
      suspension of occlusion bodies (OBs), OBs added to macerates of non-infected
      larvae and OBs in macerates of diseased larvae were 7.8 x 10(3), 7.8 x 10(3), and
      1.5 x 10(3) OBs, respectively. Purified viral DNA was detected at a concentration
      of 1.6 x 10(-1) ng in a 20 microliters volume. The presence of pre-occluded viral
      nucleocapsids and DNA, inherent to infected larvae, improved the detection
      threshold five-fold compared with OBs alone. Larval tissues did not block the
      detection system utilized, nor did they bind non-specifically to the probe.
      Detection thresholds, upon sequential hybridization of the same membrane, on
      average deteriorated two-fold between the first and second hybridization and an
      additional six-fold between the second and third hybridization. NPV infection was
      detected two days post-inoculation (pi) in about one-third of the larvae examined
      and in almost all larvae three days pi. Microscopic analysis of stained larval
      smears missed NPV infection in almost all larvae two days pi and about two-thirds
      of the larvae three days pi. Results from the two methods of analysis were not
      comparable until four days pi. The detection system utilized is a reliable,
      efficient and simple method for the early detection of NPV infection in large
      numbers of larvae and may be used for further studies quantifying the role of
      this baculovirus in the ecology of whitemarked tussock moth populations.

PMID- 11455635
TI  - The effect of initial concentration of carbofuran on the development and
      stability of its enhanced biodegradation in top-soil and sub-soil.
AB  - Carbofuran was incubated in top-soil and sub-soil samples from a pesticide-free
      site at a range of initial concentrations from 0.1 to 10 mg kg-1. Amounts of the
      incubated soils were removed at intervals over the subsequent 12 months, and the
      rate of degradation of a second carbofuran dose at 10 mg kg-1 was assessed. An
      applied concentration as low as 0.1 mg kg-1 to top-soil resulted in more rapid
      degradation of the fresh addition of carbofuran for at least 12 months. The
      degree of enhancement was generally more pronounced with the higher initial
      concentrations. When the same study was conducted in sub-soil samples from the
      same site, an initial dose of carbofuran at 0.1 mg kg-1 resulted in only small
      increases in rates of degradation of a second carbofuran dose. However,
      degradation rates in the sub-soil samples were, in many instances, considerably
      greater than in the corresponding top-soil samples, irrespective of pre-treatment
      concentration or pre-incubated period. Initial doses of 0.5 mg kg-1 and higher
      applied to sub-soil successfully activated the sub-soil microflora. Application
      of the VARLEACH model to simulate carbofuran movement through the soil profile
      indicated that approximately 0.01 mg kg-1 of carbofuran may reach a depth of 70
      cm 400 days after a standard field application. The results therefore imply that
      adaptation of the sub-soil microflora (c 1 m depth) by normal field rate
      applications of carbofuran is unlikely to occur. In experiments to investigate
      this in soils exposed to carbofuran in the field, there was no apparent
      relationship between top-soil exposure and degradation rates in the corresponding
      sub-soils. The results further confirmed that same sub-soil samples have an
      inherent capacity for rapid biodegradation of carbofuran. The high levels of
      variability observed between replicates in some of the sub-soil samples were
      attributed to the uneven distribution of a low population of carbofuran-degrading
      micro-organisms in sub-surface soil. There was no apparent relationship between
      soil microbial biomass and degradation rates within or between top-soil and sub
      soil samples.

PMID- 11455636
TI  - The status and development of insecticide resistance in Danish populations of the
      housefly Musca domestica L.
AB  - Samples of housefly (Musca domestica) field populations were collected from
      Danish livestock farms in 1997. The tolerance of the first-generation offspring
      was determined for a number of insecticides. Dose-response values were obtained
      by topical application for the pyrethroids bioresmethrin and pyrethrum, both
      synergised with piperonyl butoxide, and the organophosphate dimethoate. The
      organophosphates azamethiphos and propetamphos and the carbamate methomyl were
      tested in discriminating dose feeding bioassays. Resistance was low to moderate
      in most of the populations for most of the compounds tested, but this study also
      revealed the existence of high resistance to pyrethroid, organophosphate and
      carbamate insecticides in some populations. The resistance factors at LD50 for
      bioresmethrin/piperonyl butoxide ranged between 2 and 98, and for
      pyrethrum/piperonyl butoxide between 2 and 29. Our results indicate that
      pyrethroid resistance in Denmark is increasing, since four of the 21 farms showed
      more than 100-fold resistance at LD95, a level of resistance only observed once
      before. Resistance factors at LD50 for dimethoate ranged from 9 to 100, and
      showed two distinct trends: populations with either decreasing or increasing
      resistance. Resistance to azamethiphos was found to be widespread and high.
      Although two strains with high methomyl and propetamphos resistance were
      observed, methomyl and propetamphos resistance is moderate and appears not to be
      increasing.

PMID- 11455637
TI  - Optimum timing of insecticide applications against diamondback moth Plutella
      xylostella in cole crops using threshold catches in sex pheromone traps.
AB  - Field trials were conducted in cabbage (Brassica oleracea var capitata),
      cauliflower (B oleracea var botrytis) and knol khol (B oleracea gongylodes) crops
      at two different locations in Karnataka State (India) to optimize the timing of
      insecticide applications to control the diamondback moth, Plutella xylostella,
      using sex pheromone traps. Our results indicate that applications of cartap
      hydrochloride as insecticide during a 12-24 h period after the pheromone traps
      had caught on average 8, 12 and 16 males per trap per night in cabbage,
      cauliflower and knol khol, respectively, were significantly more effective than
      regular insecticide sprays at 7, 9, 12 or 15 days after transplantation. This was
      demonstrated by estimation of the mean number of eggs and larvae per plant, the
      percentage of holes produced, as well as the marketable yield of the three crops
      at each location. A good correlation between the immature stages, infestation
      level, the estimated crop yield and the number of moths caught in pheromone traps
      was also found, indicating the usefulness of pheromone-based monitoring traps to
      predict population densities of the pest.

PMID- 11455638
TI  - Pesticidal properties of parthenin (from Parthenium hysterophorus) and related
      compounds.
AB  - Eleven sesquiterpene lactone derivatives of parthenin (1), obtained from wild
      feverfew, Parthenium hysterophorus, were prepared by chemical and photochemical
      transformations. The compounds tested were a pyrazoline adduct (2) of parthenin,
      its cyclopropyl (3) and propenyl (4) derivatives, anhydroparthenin (5), a dihydro
      deoxygenated product (6), a formate (7) and its corresponding alcohol (8) and
      acetate (9), a rearranged product (10), lactone (11) and hemiacetal (12). All
      these derivatives, along with parthenin, were tried for their antifeedant action
      against sixth-instar larvae of Spodoptera litura, for insecticidal activity
      against the adults of store grain pest Callosobruchus maculatus, for phytotoxic
      activity against Cassia tora, and for nematicidal activity against the juvenile
      stage-II (J2) of the root knot nematode Meloidogyne incognita. Antifeedent
      bioassay revealed that parthenin is moderately antifeedant. Among the
      derivatives, the saturated lactone (11) was found to be about 2.25 times more
      active than parthenin. The pyrazoline adduct (2) was found to be the most
      effective as an insecticide, with LC50 values after 24, 48 and 72 h of 96, 43 and
      32 mg litre-1, respectively, which are comparable with neem extract. Compound 4
      was found to be the most effective inhibitor of germination and seedling growth
      of C tora, with ID50 values for germination, plumule length and radicle length of
      136, 326 and 172 compared with 364, 738 and 427 mg litre-1, respectively, for
      parthenin. Compound 10 was found to be the most effective in terms of nematicidal
      activity. The LC50 values for this compound were 273 and 104 mg litre-1,
      respectively, after 48 and 72 h compared with 862 and 512 mg litre-1 observed for
      parthenin after 48 and 72 h.

PMID- 11455639
TI  - John Grey Dingwall 1943-2000.

PMID- 11455641
TI  - The chemical and biological properties of methoxyfenozide, a new insecticidal
      ecdysteroid agonist.
AB  - Methoxyfenozide [N-tert-butyl-N'-(3-methoxy-o-toluoyl)-3,5-xylohydrazide; RH
      2485] is the newest diacylhydrazine insecticide to reach the marketplace. It
      binds with very high affinity to the ecdysone receptor complex (EcR:USP) in
      lepidopteran insects [Kd = 0.5 nM (Plodia)], where it functions as a potent
      agonist, or mimic, of the insect molting hormone, 20-hydroxyecdysone (20E).
      Methoxyfenozide exhibits high insecticidal efficacy against a wide range of
      important caterpillar pests, including many members of the family Pyralidae,
      Pieridae, Tortricidae and Noctuidae. It is most effective when ingested by the
      target caterpillar, but it also has some topical and ovicidal properties. It is
      modestly root systemic, but not significantly leaf-systemic. Evidence collected
      to date indicates that methoxyfenozide has an excellent margin of safety to non
      target organisms, including a wide range of non-target and beneficial insects.

PMID- 11455642
TI  - Mesotrione: a new selective herbicide for use in maize.
AB  - Mesotrione is a new herbicide being developed for the selective pre- and post
      emergence control of a wide range of broad-leaved and grass weeds in maize (Zea
      mays). It is a member of the benzoylcyclohexane-1,3-dione family of herbicides,
      which are chemically derived from a natural phytotoxin obtained from the
      Californian bottlebrush plant, Callistemon citrinus. The compound acts by
      competitive inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD),
      a component of the biochemical pathway that converts tyrosine to plastoquinone
      and alpha-tocopherol. Mesotrione is an extremely potent inhibitor of HPPD from
      Arabidopsis thaliana, with a Ki value of c 6-18 pM. It is rapidly taken up by
      weed species following foliar application, and is distributed within the plants
      by both acropetal and basipetal movement. Maize is tolerant to mesotrione as a
      consequence of selective metabolism by the crop plant. Slower uptake of
      mesotrione, relative to susceptible weed species, may also contribute to its
      utility as a selective herbicide for use in maize.

PMID- 11455643
TI  - Delivery of biological performance via micro-encapsulation formulation chemistry.
AB  - Lambda-cyhalothrin micro-capsules have been prepared by a novel in situ
      procedure. Manipulation of the chemistry has led to slow- and fast-release
      formulations. The latter has a biological performance comparable to commercial
      lambda-cyhalothrin emulsifiable concentrates, but exhibits a significantly
      improved toxicological profile over EC, WP and WG formulations. Micro
      encapsulation technology satisfies many of the drivers towards the safer use of
      pesticides.

PMID- 11455644
TI  - Isoxaflutole: the background to its discovery and the basis of its herbicidal
      properties.
AB  - This paper reviews the discovery of isoxaflutole (IFT), focusing on the chemical
      and physicochemical properties which contribute to the herbicidal behaviour of
      this new herbicide. IFT (5-cyclopropyl-1,2-isoxazol-4-yl alpha alpha alpha
      trifluoro-2-mesyl-p-tolyl ketone) is a novel herbicide for pre-emergence control
      of a wide range of important broadleaf and grass weeds in corn and sugarcane. The
      first benzoyl isoxazole lead was synthesised in 1989 and IFT in 1990, and the
      herbicidal potential of the latter was identified in 1991. The decision to
      develop the molecule was taken after two years of field testing in North America.
      The biochemical target of IFT is 4-hydroxyphenylpyruvate dioxygenase (HPPD),
      inhibition of which leads to a characteristic bleaching of susceptible species.
      The inhibitor of HPPD is the diketonitrile derivative of IFT formed from opening
      of the isoxazole ring. The diketonitrile (DKN) is formed rapidly in plants
      following root and shoot uptake. The DKN is both xylem and phloem mobile leading
      to high systemicity. IFT also undergoes conversion to the DKN in the soil. The
      soil half-life of IFT ranges from 12 h to 3 days under laboratory conditions and
      is dependent on several factors such as soil type, pH and moisture. The log P of
      IFT is 2.19 and the water solubility is 6.2 mg litre-1, whereas the corresponding
      values for the DKN are 0.4 and 326 mg litre-1, respectively. These properties
      restrict the mobility of IFT, which is retained at the soil surface where it can
      be taken up by surface-germinating weed seeds. The DKN, which has a laboratory
      soil half-life of 20-30 days, is more mobile and is taken up by the roots. In
      addition to influencing the soil behaviour of IFT and DKN, the greater
      lipophilicity of IFT leads to greater uptake by seed, shoot and root tissues. In
      both plants and soil, the DKN is converted to the herbicidally inactive benzoic
      acid. This degradation is more rapid in maize than in susceptible weed species
      and this contributes to the mechanism of selectivity, together with the greater
      sowing depth of the crop.

PMID- 11455645
TI  - Famoxadone: the discovery and optimisation of a new agricultural fungicide.
AB  - Famoxadone (3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione), is
      a new agricultural fungicide recently commercialized by DuPont under the trade
      name Famoxate. Famoxadone is a member of a new class of oxazolidinone fungicides
      that demonstrate excellent control of plant pathogens in the Ascomycete,
      Basidiomycete, and Oomycete classes that infect grapes, cereals, tomatoes,
      potatoes and other crops. DuPont's entry into the oxazolidinone area resulted
      from the procurement of 5-methyl-5-phenyl-3-phenylamino-2-thioxo-4-oxazolidinone
      (1) from Professor Detlef Geffken, then at the University of Bonn. An extensive
      analog program was initiated immediately after the fungicidal activity of 1 was
      discovered through routine greenhouse testing. The discovery program in the
      oxazolidinone area eventually culminated in the advancement of famoxadone to
      commercial development in the early 1990s. The synthesis of various oxazolidinone
      ring systems and the development of the structure-activity relationships that led
      to the discovery of famoxadone are described.

PMID- 11455646
TI  - The discovery of indoxacarb: oxadiazines as a new class of pyrazoline-type
      insecticides.
AB  - The evolution of the insecticidal pyrazoline moiety that was originally
      discovered in 1972 has led to the discovery of a new crop insecticide,
      indoxacarb, which is the first commercialized pyrazoline-type sodium-channel
      blocker. Both monocyclic and fused-tricyclic pyrazolines and pyridazines, as well
      as structurally related semicarbazones were examined prior to the discovery of
      analogous tricyclic oxadiazines which had similarly high activity as well as
      favorable environmental dissipation rates and low toxicity to non-target
      organisms. The eventual leading candidate, DPX-JW062, was originally obtained as
      a racemic molecule, but a chiral synthesis was developed which produces material
      that is 50% ee in the insecticidal (+)-S-enantiomer (DPX-MP062, indoxacarb).

PMID- 11455647
TI  - The discovery of thiamethoxam: a second-generation neonicotinoid.
AB  - Neonicotinoids represent a novel and distinct chemical class of insecticides with
      remarkable chemical and biological properties. In 1985, a research programme was
      started in this field, in which novel nitroimino heterocycles were designed,
      prepared and assayed for insecticidal activity. The methodology for the synthesis
      of 2-nitroimino-hexahydro-1,3,5-triazines, 4-nitroimino-1,3,5-oxadiazinanes and 4
      nitroimino-1,3,5-thiadiazinanes is outlined. Bioassays demonstrated that 3-(6
      chloropyridin-3-ylmethyl)-4-nitroimino-1,3,5-oxadiazinane exhibited better
      insecticidal activity than the corresponding 2-nitroimino-hexahydro-1,3,5
      triazine and 4-nitroimino-1,3,5-thiadiazinane. In most tests, this compound was
      equally or only slightly less active than imidacloprid. A series of structural
      modifications on this lead structure revealed that replacement of the 6-chloro-3
      pyridyl group by a 2-chloro-5-thiazolyl moiety resulted in a strong increase of
      activity against chewing insects, whereas the introduction of a methyl group as
      pharmacophore substituent increased activity against sucking pests. The
      combination of these two favourable modifications led to thiamethoxam (CGA 293
      343). Thiamethoxam is the first commercially available second-generation
      neonicotinoid and belongs to the thianicotinyl sub-class. It is marketed under
      the trademarks Actara for foliar and soil treatment and Cruiser for seed
      treatment. The compound has broad-spectrum insecticidal activity and offers
      excellent control of a wide variety of commercially important pests in many
      crops. Low use rates, flexible application methods, excellent efficacy and the
      favourable safety profile make this new insecticide well-suited for modern
      integrated pest management programmes in many cropping systems.

PMID- 11455648
TI  - Recent advances in the chemistry of spinosyns.
AB  - The spinosyns are a new class of fermentation-derived insect control agents that
      are effective against a variety of chewing insect pests. The successful
      introduction of spinosad into the agricultural marketplace represents an
      important milestone in the use of natural products for commercial pest control.
      The development of a natural product presents additional limitations relative to
      a synthetic material. While the latter affords some degree of control in building
      appropriate physical attributes such as photostability, a natural product,
      designed to function in a different environment, is often less suited for
      traditional spray applications. Despite its intrinsic photolability, spinosad is
      stable enough to perform under field conditions. In an effort to generate analogs
      with improved physical characteristics, we have developed a variety of conditions
      for selectively modifying different portions of the molecule, and we have
      discovered analogs with greater activity against a broader spectrum of pests. The
      inability to translate improved greenhouse activity to actual field conditions
      resulted in a detailed study of the effects of formulations and crystallinity on
      biological activity. Through this effort, measurably improved field performance
      of synthetic spinosyn analogs relative to the natural product have now been
      observed.

PMID- 11455649
TI  - Comparative evaluation of new synergists containing a butynyl-type synergophore
      group and piperonyl butoxide derivatives.
AB  - Cross-substituted derivatives of piperonyl butoxide (PBO) and MB-599 (proposed
      common name: verbutin) were synthesized and investigated as carbofuran and
      permethrin synergists against housefly, Musca domestica L. The majority of PBO
      and MB-599 derivatives were significantly more potent synergists for carbofuran
      than for permethrin. PBO, the most important representative of this series was
      not the most potent synergist for carbofuran or for permethrin. Cleavage of the
      methylenedioxy ring of methylenedioxyphenyl (MDP) polyether compounds resulted in
      complete loss of synergistic activity with both insecticides, but it could be
      restored or even improved by incorporating an alkynyl ether moiety into the
      molecule. The improved synergistic activity was found to be closely associated
      with the 2-butynyloxymethyl side-chain, suggesting that this can be regarded as a
      characteristic synergophore group. MB-599, one of the most promising compounds
      bearing this group showed considerably higher activity with carbofuran (synergist
      ratio, SR = 37.8) than with PBO (SR = 6.4). There was no significant difference
      between synergistic activities of MB-599 (SR = 4.6) and PBO (SR = 4) for
      permethrin.

PMID- 11455650
TI  - Synthesis and structure-activity relationships of benzophenone hydrazone
      derivatives with insecticidal activity.
AB  - A broad range of benzophenone hydrazone derivatives was prepared and tested
      against selected chewing insect pests, allowing the analysis of structure
      activity relationships. Good activity was found only when the aromatic rings were
      substituted at the 4-positions with an halogen atom and a triflate or
      perhaloalkoxy group. In contrast, a number of substituents on the hydrazone part
      led to active compounds, the best results being achieved with acyl-type
      substituents. The excellent laboratory and greenhouse activity of the best
      representatives was confirmed in semi-field trials against Spodoptera littoralis.

PMID- 11455651
TI  - 7-(4,6-Dimethoxypyrimidinyl)oxy- and -thiophthalides as novel herbicides: Part 1.
      CGA 279 233: a new grass-killer for rice.
AB  - A series of novel types of 7-(4,6-dimethoxypyrimidin-2-yl)oxy- and -thio-3-methyl
      1 (3H)-isobenzofuranones were discovered at Dr R Maag AG. From the thio
      isobenzofuranyl series, CGA 279 233--BSI-proposed common name pyriftalid--was
      chosen for further development as a grass herbicide for use in rice. General
      synthetic approaches to these new phthalic acid-derived compounds are given, with
      emphasis on the synthesis of pyriftalid and its physico-chemical behaviour.

PMID- 11455652
TI  - Risk posed to honeybees (Apis mellifera L, Hymenoptera) by an imidacloprid seed
      dressing of sunflowers.
AB  - In a greenhouse metabolism study, sunflowers were seed-treated with radiolabelled
      imidacloprid in a 700 g kg-1 WS formulation (Gaucho WS 70) at 0.7 mg AI per seed,
      and the nature of the resulting residues in nectar and pollen was determined.
      Only the parent compound and no metabolites were detected in nectar and pollen of
      these seed-treated sunflower plants (limit of detection < 0.001 mg kg-1). In
      standard LD50 laboratory tests, imidacloprid showed high oral toxicity to
      honeybees (Apis mellifera), with LD50 values between 3.7 and 40.9 ng per bee,
      corresponding to a lethal food concentration between 0.14 and 1.57 mg kg-1. The
      residue level of imidacloprid in nectar and pollen of seed-treated sunflower
      plants in the field was negligible. Under field-growing conditions no residues
      were detected (limit of detection: 0.0015 mg kg-1) in either nectar or pollen.
      There were also no detectable residues in nectar and pollen of sunflowers planted
      as a succeeding crop in soils which previously had been cropped with imidacloprid
      seed-treated plants. Chronic feeding experiments with sunflower honey fortified
      with 0.002, 0.005, 0.010 and 0.020 mg kg-1 imidacloprid were conducted to assess
      potential long-term adverse effects on honeybee colonies. Testing end-points in
      this 39-day feeding study were mortality, feeding activity, wax/comb production,
      breeding performance and colony vitality. Even at the highest test concentration,
      imidacloprid showed no adverse effects on the development of the exposed bee
      colonies. This no-adverse-effect concentration of 0.020 mg kg-1 compares with a
      field residue level of less than 0.0015 mg kg-1 (= limit of detection in the
      field residue studies) which clearly shows that a sunflower seed dressing with
      imidacloprid poses no risk to honeybees. This conclusion is confirmed by
      observations made in more than 10 field studies and several tunnel tests.

PMID- 11455653
TI  - Uptake and translocation of carpropamid in rice (Oryza sativa L).
AB  - Translocation of the antiblast compound, carpropamid, was investigated in rice
      using [14C]carpropamid. When applied to the seed, carpropamid was not only
      readily absorbed but was translocated to different parts of the seedlings
      emerging from treated seeds. A substantial portion of fungicide appeared to be
      exuded onto the leaf surface. In 21-day-old plants grown from [14C]carpropamid
      treated seeds, 27.2% of the radioactivity isolated from leaves was present on the
      surface of lamina. This exuded fraction is probably responsible for its action as
      a fungal anti-penetrant compound. Following 30-min root dipping of 14-day-old
      seedlings, carpropamid was rapidly absorbed and translocated throughout the
      seedling. Its intra-laminar distribution was uniform as determined by
      autoradiography. Only a small fraction (< 2%) of fungicide applied to the foliage
      was translocated beyond the site of application within the treated leaf.
      Translocation was primarily apoplastic. Approximately 54% of the radioactivity
      recovered from leaves was in the form of carpropamid. At least seven
      radiolabelled metabolic products were observed by TLC. Only 8.3% of radioactivity
      applied through the seeds could be recovered from 21-day-old seedlings.

PMID- 11455654
TI  - Aversion of the feral pigeon and the house sparrow to pellets and sprouts treated
      with commercial formulations of methyl anthranilate.
AB  - Two methyl anthranilate formulations, ReJex-iT TP-40 and AG-36, were tested as
      bird-repelling agents for animal feed and vegetable sprouts, respectively. Feral
      pigeons (Columbia livia) and house sparrows (Passer domesticus) are important
      pests of animal husbandry and field crops in Israel. In each 4-day experiment,
      four birds were held together in an aviary, and were offered four trays or dishes
      with animal feed or cauliflower sprouts in four corners of the cage. The trays
      and dishes were transposed daily in a Latin square sequence. Pigeons consumed
      significantly more untreated feed than treated feed. When no alternative
      untreated food was offered, there was no significant repellency. Treatment of
      animal feed with TP-40 to give 2.0 ml methyl anthranilate kg-1 or less had no
      repellent effect on sparrows. Concentrations of 4.0 ml kg-1 or more repelled the
      sparrows significantly. When no untreated feed was presented, pigeons and
      sparrows preferred the lowest concentration of methyl anthranilate presented.
      When AG-36 was tested on vegetable sprouts, the sparrows tended significantly to
      avoid the highest concentration used--14.5 ml methyl anthranilate litre-1 spray.
      The inter-specific differences between the birds indicate that the efficacy of
      methyl anthranilate formulations as a repellent has to be specified for every
      species. This study did not determine (1) the possibility of developing
      habituation, (2) the behaviour of birds under natural conditions in the field, or
      (3) the influence of the feeding behaviour of a sympatric bird species on the
      repellency of methyl anthranilate to other species.

PMID- 11455655
TI  - Acaricide toxicity and resistance in larvae of different strains of Tetranychus
      urticae and Panonychus ulmi (Acari: Tetranychidae).
AB  - The toxicities of eight structurally different acaricidal compounds to six-legged
      larvae (first motile stage) of three laboratory strains of the two-spotted spider
      mite, Tetranychus uritcae, and the European red mite, Panonychus ulmi, were
      evaluated following spray application. The larvae of five field-derived strains
      of T urticae originating from France, Italy, Brazil, California and Florida were
      also tested for their susceptibilities to discriminating concentrations of
      several acaricides resulting in 95% mortality when applied to the organophosphate
      resistant laboratory reference strain WI. The spray bioassay used was robust and
      gave repeatable results with a wide range of acaricidal compounds, irrespective
      of their mode of action (ovo-larvicides or primarily acting on motile life
      stages). Compounds tested were abamectin, azocyclotin, chlorpyrifos,
      clofentezine, deltamethrin, fenpyroximate, hexythiazox and pyridaben. Larvae of
      one of the laboratory strains of T urticae, AK, originally collected in Japan in
      1996 and maintained without further selection pressure, exhibited 2000- and >
      4000-fold resistance to the mitochondrial electron transport inhibitors pyridaben
      and fenpyroximate, respectively. Another strain of T urticae, AU, obtained from
      Australia and maintained in the laboratory under selection with hexythiazox and
      clofentezine since 1987 showed > 770- and > 1000-fold resistance to clofentezine
      and hexythiazox, respectively. The same resistance pattern was observed against
      larvae of a laboratory strain of P ulmi, CE, also selected with hexythiazox.
      Larvae of one of the field-derived strains of T urticae, BR, showed a lower
      susceptibility to a number of compounds, whilst the others were susceptible to
      all compounds except the organophosphates.

PMID- 11455656
TI  - Persistence and translocation of a benzothiadiazole derivative in tomato plants
      in relation to systemic acquired resistance against Pseudomonas syringae pv
      tomato.
AB  - A reproducible and accurate procedure, based on HPLC analysis, has been developed
      to determine simultaneously acibenzolar-S-methyl (CGA 245 704) and its acid
      derivative (CGA 210 007) in tomato leaves. The limit of detection and
      quantification of the method are 0.015 and 0.15 mg litre-1 for CGA 245 704 and
      0.030 and 0.30 mg litre-1 for CGA 210 007. In tomato plants treated with 250
      microM CGA 245 704, it was found that the inducer rapidly translocates from
      treated leaves (cotyledons, 1st and 2nd) to untreated leaves (3rd to 5th), with
      the maximum translocation (40% of the total quantity found) occurring 8 h after
      the treatment. CGA 245 704 residues decreased as time elapsed in both treated and
      untreated tomato leaves, reaching negligible values 72 h after treatment. The
      acid derivative, CGA 210 007, was formed in tomato plants as early as 2 h after
      CGA 245 704 treatment, albeit only in the treated leaves. CGA 210 007 residues
      decreased in treated tomato leaves with a trend similar to that observed for CGA
      245 704. Treatment of tomato plants with CGA 245 704 or CGA 210 007 at 250 microM
      systemically protected the plants against Pseudomonas syringae pv tomato attacks,
      the causal agent of bacterial speak disease. Evidence of this were reductions in
      the degree of infection, the bacterial lesion diameter and the bacterial growth
      in planta. Since neither CGA 245 704 nor CGA 210 007 inhibited bacterial growth
      in vitro and the protection against bacterial speak of tomato was observed when
      the two compounds were completely degraded, the protection must be due to the
      activation of the plant's defence mechanisms.

PMID- 11455657
TI  - A monoclonal antibody-based ELISA for the analysis of the insecticide
      flucythrinate in environmental and crop samples.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) has been developed for
      the detection of the insecticide flucythrinate in environmental and food samples.
      Two types of haptens, the acid moiety that is the hydrolyzed product of
      flucythrinate, and the carboxylated propyl derivative of the alcohol moiety, were
      used to prepare monoclonal antibodies (MAbs). Five MAbs, which raised against the
      former hapten, were reactive with flucythrinate. Among them, MAb F1A27-4 showed
      the highest activity toward flucythrinate, and did not cross-react with other
      pyrethroids such as cycloprothrin, fenvalerate, fluvalinate, etofenprox and
      silafluofen. The assay conditions of indirect competitive ELISA with MAb F1A27-4
      were studied to optimize the detection of flucythrinate in environmental and food
      samples. Incubation at 4 degrees C in the assay buffer, pH 8, with 300 mM sodium
      chloride improved the sensitivity. The addition of rabbit serum albumin or rabbit
      antiserum and the presence of 50 ml litre-1 of methanol reduced matrix effects of
      the samples. Under optimized conditions, the ELISA detected flucythrinate spiked
      in water, soil, and extracts of apple and tea samples down to 10 mg litre-1, 0.2
      mg litre-1, 0.3 mg litre-1 and 0.3 mg litre-1, respectively. The mean recovery
      and CV ranged from 91% to 120% and from 5% to 12%, respectively. The ELISA
      results in apple samples correlated well with those from LC-MS analysis (r2 =
      0.99, n = 12).

PMID- 11455658
TI  - Mode of action of new diethylamines in lycopene cyclase inhibition and in
      photosystem II turnover.
AB  - The new bleaching herbicidal compound N,N-diethyl-N-(2-undecynyl)amine (NDUA) is
      identified here as an inhibitor of lycopene cyclase and is compared with the
      known cyclase inhibitors N,N-diethyl-N-[2-(4-chlorophenylthio)ethyl]amine (CPTA)
      and N,N-diethyl-N-[2-(4-methylphenoxy)ethyl]amine (MTPA). HPLC separation of
      chloroplast pigments shows lycopene accumulation in NDUA treated tissue.
      Variation in chain length of the undecynylamine moeity of NDUA from 7 to 21 C
      atoms reveals an optimum of 11 to 14 C atoms for herbicidal activity. A series of
      seven further analogues of NDUA and CPTA reveals the structural elements
      necessary for inhibition of lycopene cyclase. The effect of NDUA derivatives on
      photosynthesis has been studied in Chlamydomonas reinhardtii. Photosynthesis is
      highly sensitive, particularly towards the C14 and longer chain length analogues
      at nanomolar concentrations. It is shown that the breakdown of photosynthesis by
      NDUA is due to interference with the turnover of the D1 protein of the
      photosystem II reaction centre that requires the continuous biosynthesis of the
      two reaction-centre beta-carotene moieties in the reassembly phase. The D1
      protein disappearance is most marked under strong light conditions. The depletion
      of photosystem II occurs before total pigment bleaching. This newly recognized
      mechanism in herbicidal activity is also the basis for the mode of action of
      other lycopene cyclase inhibitors as well as phytoene desaturase inhibitors.

PMID- 11455659
TI  - Involvement of cytochrome P-450 enzyme activity in the selectivity and safening
      action of pyrazosulfuron-ethyl.
AB  - To investigate the selectivity and safening action of the sulfonylurea herbicide
      pyrazosulfuron-ethyl (PSE), pyrazosulfuron-ethyl O-demethylase (PSEOD) activity
      involving oxidative metabolism by cytochrome P-450 was studied in rice (Oryza
      sativa L cv Nipponbare) and Cyperus serotinus Rottb. Cytochrome P-450-dependent
      activity was demonstrated by the use of the inducers 1,8-naphthalic anhydride and
      ethanol, the herbicides PSE, bensulfuron-methyl, dimepiperate and dymron, or the
      inhibitor piperonyl butoxide (PBO). Growth inhibition in C serotinus seedlings
      was more severe than that in rice seedlings. O-Dealkylation activities of PSE
      were induced differently in rice and in C serotinus, with distinctly higher
      activity in rice seedlings. The induced PSEOD activities were slightly inhibited
      by PBO in rice seedlings, whereas they were strongly inhibited in C serotinus
      seedlings. Dimepiperate and dymron were effective safeners of rice against PSE
      treatment. Treatments with herbicide alone resulted in less induction of PSEOD
      activity compared with combined treatments of the herbicide and safener. PSEOD
      activity in rice seedlings induced with herbicide alone was strongly inhibited by
      PBO, whereas it was weakly inhibited in rice seedlings induced with combinations
      of PSE and two safeners. These results suggest that O-demethylation by cytochrome
      P-450 enzymes may be involved in the metabolism of PSE and may contribute to its
      selectivity and safening action. Furthermore, these results suggest the existence
      of a multiple form of cytochrome P-450 in plants.

PMID- 11455660
TI  - Insect growth inhibition, antifeedant and antifungal activity of compounds
      isolated/derived from Zingiber officinale Roscoe (ginger) rhizomes.
AB  - Fresh rhizomes of Zingiber officinale (ginger), when subjected to steam
      distillation, yielded ginger oil in which curcumene was found to be the major
      constituent. The thermally labile zingiberene-rich fraction was obtained from its
      diethyl ether extract. Column chromatography of ginger oleoresin furnished a
      fraction from which [6]-gingerol was obtained by preparative TLC. Naturally
      occurring [6]-dehydroshogaol was synthesised following condensation of
      dehydrozingerone with hexanal, whereas zingerone and 3-hydroxy-1-(4-hydroxy-3
      methoxyphenyl)butane were obtained by hydrogenation of dehydrozingerone with 10%
      Pd/C. The structures of the compounds were established by 1H NMR, 13C NMR and
      mass (EI-MS and ES-MS) spectral analysis. The test compounds exhibited moderate
      insect growth regulatory (IGR) and antifeedant activity against Spilosoma
      obliqua, and significant antifungal activity against Rhizoctonia solani. Among
      the various compounds, [6]-dehydroshogaol exhibited maximum IGR activity (EC50
      3.55 mg ml-1), while dehydrozingerone imparted maximum antifungal activity (EC50
      86.49 mg litre-1).

PMID- 11455661
TI  - Contact and fumigant activities of constituents of Foeniculum vulgare fruit
      against three coleopteran stored-product insects.
AB  - The insecticidal activities of materials derived from the fruit of fennel,
      Foeniculum vulgare, against adults of Sitophilus oryzae, Callosobruchus chinensis
      and Lasioderma serricorne were examined using direct contact application and
      fumigation methods. The biologically active constituents of the Foeniculum fruits
      were characterized as the phenylpropenes (E)-anethole and estragole, and the
      monoterpene (+)-fenchone, by spectroscopic analysis. Responses varied with insect
      species, compound, dose and exposure time. In a filter paper diffusion test,
      estragole at 0.168 mg cm-2 caused 91% mortality to S oryzae adults within 1 day
      after treatment (DAT), whereas (+)-fenchone and (E)-anethole gave over 90%
      mortality at 2 and 4 DAT, respectively. Against C chinensis adults, all test
      compounds revealed potent insecticidal activities at 0.021 mg cm-2 at 2 DAT.
      Against L serricorne adults at 0.105 mg cm-2, (E)-anethole gave 100% mortality at
      1 DAT, whereas 90 and 60% mortality at 4 DAT was achieved with estragole and (+)
      fenchone, respectively. In a fumigation test, the compounds were much more
      effective against adults of S oryzae, C chinensis and L serricorne in closed cups
      than in open ones, indicating that the insecticidal activity of test compounds
      was largely attributable to fumigant action. As naturally occurring insect
      control agents, the F vulgare fruit-derived materials described could be useful
      for managing field populations of S oryzae, C chinensis and L serricorne.

PMID- 11455662
TI  - Activity of the botanical aphicides 1,5-diphenyl-1-pentanone and 1,5-diphenyl-2
      penten-1-one on two species of Aphididnae.
AB  - 1,5-Diphenyl-1-pentanone (A) and 1,5-diphenyl-2-penten-1-one (B) are natural
      products extracted for the first time from Stellera chamaejasme. Laboratory
      bioassay showed that the two products have strong contact activity and very good
      anti-feedant activity against Aphis gossypii and Schizaphis graminum. Both
      products showed dose-dependent relationships for both forms of activity against
      the two aphids, the contact activity of B being about twice that of A. Both
      products were inferior to methomyl in contact activity but superior in anti
      feedant activity against the two aphids. This is the first report of aphicidal
      activity in these two compounds, which may represent a new class of aphicide.

PMID- 11455663
TI  - Toxico-kinetics, recovery efficiency and microsomal changes following
      administration of deltamethrin to black Bengal goats.
AB  - A study of the toxico-kinetics, recovery percentage from different substrates,
      cytotoxicity and role of cytochrome P450 and b5 of liver microsome in the
      metabolism of deltamethrin were carried out in female black Bengal goat. The
      ALD50 value of deltamethrin in goat by intravenous route lies between 0.2 and 0.6
      mg kg-1. Intravenous disposition kinetics using a dose of 0.2 mg kg-1 showed that
      the maximum blood concentration of deltamethrin was recorded at 0.5 min, followed
      by rapid decline, and a minimum concentration was detected at 6 min after
      administration. The following values were obtained: Vdarea 0.148 (+/- 0.02) litre
      kg-1; t1/2 (alpha) 0.22 (+/- 0.02) min; t1/2 (beta) 2.17 (+/- 0.37) min; Kel 1.05
      (+/- 0.24) min-1; AUC 4.30 (+/- 0.45) micrograms min ml-1; ClB 0.05 (+/- 0.006)
      litre kg-1 min-1; T-B 1.93 (+/- 0.58); fc 0.40 (+/- 0.05). After 10 min, liver
      retained the maximum residue, and heart, adrenal gland, kidney, spleen, fat and
      brain also held the insecticide; liver, fat, heart and spleen retained residue
      after 30 min, and bone, liver and fat retained residue after 60 min of
      intravenous administration. Oral absorption of deltamethrin was poor and
      inconsistent, and approximately 65% of administered dose was recovered from
      faeces and gastrointestinal contents. The excretion of deltamethrin through urine
      was meagre, and only 0.01 and 0.013% of the administered dose was recovered after
      3 and 5 days of oral administration respectively. All the tissues retained the
      residue after 3 days; while fat, rumen, reticulum, omasum, abomasum, large and
      small intestine and bone retained the residue after 5 days of oral
      administration; and the percentage recoveries were 1.73 and 0.027 respectively.
      Deltamethrin reduced the level of cytochrome P450 content of liver microsomal
      pellet of goat after 5 days of oral administration. Histopathological examination
      of liver, kidney, heart, spleen brain and lung sections of treated goats did not
      reveal any pathological changes.

PMID- 11455664
TI  - [Stroke unit in a medical clinic: one year results and perspectives].
AB  - BACKGROUND: For patients with cerebral ischemia treatment on specialized stroke
      units is helpful. Details concerning organisation, diagnostic and therapy are
      discussed controversially. We report about a concept and the one-year results on
      a stroke unit in a major medical clinic. METHODS: The unit consists of four beds
      and is organizationally attached to the intensive care unit. Immediate diagnosis
      allows an early etiologic classification. Management of main cofactors
      (hypertension, heart rate, blood glucose, temperature) are regarded important.
      Neurologic and neuroradiologic expertise are available at any time. Patients are
      taken care of by specially trained staff (nursing/medical care, physiotherapy,
      ergotherapy, logopedics). RESULTS: Within a year (1.10.1999-30.9.2000) 340
      patients with cerebral ischemia were treated in our stroke unit (152 men, 188
      women, median age 75 years). Approximately 60% of the patients were admitted
      within 6 hours after the event. The Rankin-Scale was improved from 4 to 1, the
      Barthel-Index from 50 to 90. Over 60% of the patients were discharged home, 20%
      were transferred to a rehabilitation unit, 5% into a nursing home, 6% died. 5
      patients with carotid stenosis underwent surgical treatment. CONCLUSION:
      Effective diagnosis and treatment of stroke is achievable under certain qualified
      conditions in a medical clinic and is indispensable for sufficient care.

PMID- 11455665
TI  - [Compliance with hand hygiene in intensive care units].
AB  - INTRODUCTION: Nosocomial infections are an important problem in modern hospitals.
      The prevalence in German intensive care units is 15.3%. Hand washing or hand
      disinfection is believed to be the most important means of preventing nosocomial
      infections. We wished to answer the following questions: 1. How good is the
      compliance of hand hygiene on intensive care units? 2. Is compliance associated
      with the patient/nurse-ratio? METHOD: In a study of 8 intensive care units the
      compliance of hand hygiene was observed on two occasions, once in May 1996 and
      again in November 1997. The prime necessity for hand disinfection occurred when
      handling ventilation devices, intravascular catheters, urinary catheters and
      dressings. In addition the patient/nurse-ratio was calculated. RESULTS: A total
      of 1,879 infection-relevant handlings were observed. The compliance of hand
      hygiene ranged from 25.7 to 83.2% (mean 55.2%). The most commonly observed
      handlings were the manipulation of venous catheters (52.7%), the highest
      compliance was observed with the manipulation of ventilation equipment (91.8%).
      With a better patient nurse ratio the compliance did not improve but remained the
      same or was even reduced. DISCUSSION: The compliance of hand disinfection is
      similar to other study results, but on some intensive care units there was
      considerable room for improvement. In this study the compliance of hand hygiene
      is more of a constant factor in individual intensive care units than associated
      with the patient/nurse-ratio.

PMID- 11455666
TI  - [Cerebral tuberculosis in a patient with Sharp's syndrome].
AB  - HISTORY AND ADMISSION DIAGNOSIS: A 57-year-old female patient with fever and
      impaired consciousness was admitted to the department of neurology after her
      first epileptic seizure. She had a 9-year history of mixed connective tissue
      disease (MCTD, Sharp's syndrome) predominantly presenting with pulmonary symptoms
      and destructive arthritis. Endoprothetic surgery had to be performed several
      times and she was given long-term immunosuppressive therapy. INVESTIGATIONS:
      Cerebrospinal fluid analysis showed pleocytosis (59/mm3), high protein
      concentration (2540 mg/l) and low glucose level (31 mg/dl) compared to blood
      glucose level (122 mg/dl) the indicating possible tuberculous
      meningoencephalitis. DIAGNOSIS, TREATMENT AND COURSE: Tuberculostatic therapy was
      initiated, but despite extensive testing Mycobacterium tuberculosis could
      initially not be detected by microscopy, culture or amplification techniques
      (TMA; transcription mediated amplification). Clinical response to antituberculous
      therapy was poor and the patient developed cerebral ischaemia and hydrocephalus.
      Because of earlier histological findings from the synovialectomy showing
      epitheloid cell granuloma a knee joint specimen from a wound drainage was tested
      and extracerebral tuberculosis was finally confirmed by mycobacterial culture so
      that tuberculosis as the reason for the meningoencephalitis became highly
      probable. Despite slight improvements the patient still had hemiparesis and
      lethargy as neurological sequalae at the end of therapy. CONCLUSION: The case
      demonstrates the difficulties in the diagnosis of tuberculosis in patients with
      signs and symptoms similar for those caused by other multisystemic diseases. When
      tuberculous meningitis is considered, therapy should be initiated even in cases
      with negative microbiological tests because of severe consequences when treatment
      is delayed.

PMID- 11455667
TI  - [An uncommon cause of severe soft tissue bleeding during phenprocoumon
      treatment].
AB  - HISTORY AND ADMISSION FINDINGS: A 66-year-old patient presented to our clinic
      with extensive left arm and left flank haematomas, anaemia, a prolonged activated
      partial thromboplastin time (aPTT), and reduced factor IX activity 6 weeks after
      prosthetic mechanical aortic valve implantation. INVESTIGATION: Treatment with
      both vitamin K and a single injection of factor IX concentrate led to
      normalization of the activated partial thromboplastin time and factor IX
      activity, which remained constant for several days. No acquired factor IX
      inhibitor was detectable. Analysis of exon 2 of the factor IX gene revealed a C-
      >T mutation in codon 10 of the propeptide region, resulting in the substitution
      of alanine by valine. Echocardiography revealed a significant paravalvular leak.
      TREATMENT AND COURSE: The substitution of valine for alanine in the factor IX
      propeptide leads to an impaired affinity of factor IX to the vitamin K
      carboxylase complex. In this situation, treatment with coumarin derivatives can
      profoundly reduce factor IX activity and result in severe bleeding episodes. This
      patient was re-exposed to warfarin under close hematological monitoring. After 4
      days factor IX activity had decreased to 15%, which was associated with an
      increase of the aPTT and a mild decrease of the prothrombin time. Due to rapid
      progression of the paravalvular leak and almost impossible long-term orale
      anticoagulation with coumarin derivatives, we recommended replacement of the
      prosthetic mechanical valve with a biological device. CONCLUSION: The development
      of severe bleeding in the context of initiating warfarin therapy raises the
      suspicion of a factor IX propeptide mutation. The initial screening test is the
      activated partial thromboplastin time, which is elevated in the presence of the
      mutation. If concomitantly diminished factor IX activity is found the factor IX
      propeptide mutation should be excluded. Use of lifelong coumarin derivatives is
      contraindicated in patients with this mutation. However, a general screening of
      the activated partial thromboplastin time after coumarin initiation is not
      justified by cost/benefit analysis.

PMID- 11455668
TI  - [Short-term anesthesia to stop persistent hiccups].

PMID- 11455669
TI  - [Current therapy of Sneddon's syndrome].

PMID- 11455670
TI  - [What is certain in the topical eradication of MRSA from carriers?].

PMID- 11455671
TI  - [Ulcer prevention during long term treatment with glucocorticoids?].

PMID- 11455672
TI  - [Reference values in patients with daily alcohol consumption].

PMID- 11455673
TI  - [Benign tumors of the papilla of Vater].

PMID- 11455675
TI  - Local anaesthetic effectivity and toxicity of fomocaine, five N-free fomocaine
      metabolites and two chiralic fomocaine derivatives in rats compared with
      procaine.
AB  - Until now, no optimal local anaesthetic drug with long lasting effect and low
      toxicity has been developed. Fomocaine (CAS 17692-39-6), introduced in the German
      extrapharmacopoela (DAC) in 1979, is a local anaesthetic, which is largely in
      accordance with these aspects. Now the basic ether fomocaine, its metabolites
      O/Se 9 (CAS 3006-96-0), O/Se 10 (CAS 31719-76-3), O/Se 11, O/Se 12 (CAS 64264-21
      7) and M5 and its chiralic derivatives O/G 3 and O/G 5 were compared with
      procaine (CAS 59-46-1) and characterised more in detail in rats. The metabolism
      of fomocaine was investigated earlier with 14C-fomocaine in rats and beagle dogs.
      Rac-O/G 3 and Rac-O/G 5 could be separated into the enantiomers via the
      diastereomeric salts. Basing on standard methods for the testing of the local
      anaesthetic effects (estimation of infiltration and conduction anaesthesia in rat
      tail, measurement of corneal anaesthesia) and using a couple of tests
      characterising the side effects and toxicity of local anaesthetic (paresis of the
      N. ischiadicus, tissue irritation, determination of the approximative i.p. LD50)
      it can be concluded that: a) The very good surface anaesthesia caused by
      fomocaine could be stated, but, as expected, concerning conduction anaesthesia,
      procaine is better qualified for clinical use. b) Fomocaine is much more
      effective in conduction and surface anaesthesia than its chiralic derivatives O/G
      3 and O/G 5. c) Differences between the two enantiomers of the O/G-substances
      have been found, but these little discrepancies are without practical relevance.
      In the case of O/G 5, agonistic effects of both enantiomers could be shown. d)
      Fomocaine undergoes extensive biotransformation with subsequent formation of 14
      metabolites. Five of them (O/Se 9-O/Se 12; M5) are N-free and do not show any
      pharmacological activity. e) Compared to other local anaesthetics, fomocaine is
      relatively non-toxic (nearly no tissue irritation, high approximative LD50),
      however, surprisingly the toxicity of the reference substance procaine has been
      found to be lower after i.p. administration instead of i.v. administration in
      comparison with fomocaine.

PMID- 11455676
TI  - Comparison of the effects of three sulfonylureas on in vivo insulin action.
AB  - To clarify the diversity in hypoglycemic actions of sulfonylureas, chronic
      effects of three sulfonylureas were compared on in vivo insulin-induced glucose
      uptake in peripheral tissues. After oral administration of glimepiride (CAS 93479
      97-1), glibenclamide (CAS 10238-21-8), gliclazide (CAS 21187-98-4), or saline as
      control, two-step euglycemic clamp procedures were performed. During
      physiological hyperinsulinemia induced by 6 mU/kg/min insulin infusion, metabolic
      clearance rates (MCR) of glucose of the glimepiride-administered group (GP)
      significantly (p < 0.01) increased to 153% of the saline-administered group (SA).
      There was no significant statistical difference between the glibenclamide
      administered group (GC), gliclazide-administered group (GZ) and SA. During 30
      mU/kg/min clamps that lead to maximal insulin action, MCR of either GP or GC were
      significantly higher than those of SA (128% and 141%, p < 0.05 and p < 0.01,
      respectively). MCR of GZ were lower than those of GC (80%, p < 0.05), and showed
      no significant difference from those of SA. These data indicate that glimepiride
      activates insulin binding levels to a greater degree than the other two
      sulfonylureas, and that glibenclamide and glimepiride activate post-receptor
      binding mechanisms in peripheral tissues much more than gliclazide. These results
      suggest that hypoglycemic actions of sulfonylureas at the extra pancreatic levels
      vary with the nature of each reagent.

PMID- 11455677
TI  - Pharmacokinetics of menthol and carvone after administration of an enteric coated
      formulation containing peppermint oil and caraway oil.
AB  - Enteric coating of peppermint oil/caraway oil capsules avoids subjective
      discomfort to the patient caused by gastroesophageal reflux. In order to confirm
      bioequivalence of an enteric coated formulation containing peppermint oil and
      caraway oil (CAS 277309-55-4, Enteroplant) and an immediate release formulation
      of both oils, the pharmacokinetics of menthol and carvone after oral
      administration of the two formulations were studied in a randomized, two-period
      cross-over study in 16 healthy male volunteers. The subjects received 180 mg
      peppermint oil and 100 mg caraway oil, once as 2 enteric coated capsules of the
      fixed enteric coated combination preparation containing 90 mg peppermint oil (WS
      1340) and 50 mg caraway oil (WS 1520) each (test) and once in the form of 5
      capsules of an immediate release formulation (reference) containing 36 mg
      peppermint (WS 1340) oil and 20 mg caraway oil (WS 1520) each. The capsules were
      taken with 250 ml water after a 10 h fast. Both substances were determined in
      plasma by GC/MS after extraction. The limit of quantification was 10 ng/ml for
      menthol and 0.5 ng/ml for carvone. The mean maximum plasma levels for menthol
      were 1196 ng/ml after administration of the test medication and 1492 ng/ml after
      administration of the reference medication. The bioavailability with respect to
      the AUC was comparable after administration of test and reference preparation,
      the 90% confidence interval was 97 to 105%. As expected, there were considerable
      differences for Tmax. After application of the enteric coated form the maximum
      concentration was reached significantly later (3.0 h vs. 1.7 h) compared to the
      immediate release capsule. Corresponding data were also calculated for carvone.
      After application of the test medication the maxima of 14 ng/ml for both
      formulations were reached later (2.5 h vs. 1.3 h). The 90% confidence interval of
      the AUC for carvone was 79 to 119% and therefore slightly outside the acceptable
      range for bioequivalence of 80 to 125%. However, this fact should not be
      relevant, in particular since the dosage of the enteric coated capsule lies at
      the upper limit of the model text and positive clinical studies, also on the
      therapeutic equivalence of the two formulations, are available.

PMID- 11455678
TI  - Synthesis of some thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones and their novel
      Michael addition products with anti-inflammatory activities.
AB  - In this study, 21 new compounds having 2-methyl-6-benzylidenethiazolo[3,2-b]
      1,2,4-triazol-5(6H)-one (2-4) and 2-methyl-6-(alpha-aminobenzyl)thiazolo[3,2-b]
      1,2,4-triazole-5-ol (2a-4g) structures were synthesized. The structures of the
      compounds were proved by spectral and elemental analysis. All of the compounds
      synthesized were tested for their anti-inflammatory actively and ulcerogenic
      potential in mice at 10, 20 and 40 mg/kg dose levels. Compound 4b showed higher
      anti-inflammatory activity than the analogue derivatives and indometacin (CAS 53
      86-1), used as a reference drug, at 10 mg/kg dose level. Generally, the compounds
      were found to be more reliable than indometacin since they did not cause any
      reaction in the stomach.

PMID- 11455679
TI  - Synthesis of some new 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4
      thiadiazoles and 1,2,4-triazole-3-thiones and their anti-inflammatory activities.
AB  - Sixteen 1-(1-naphthyloxy)acetyl-4-substituted-3-thiosemicarbazides, 2-substituted
      amino-5-(1-naphthyloxy)methyl-1,3,4-oxadiazoles, 2-substitutedamino-5-(1
      naphthyloxy) methyl-1,3,4-thiadiazoles and 3-(1-naphthyloxy)methyl-4-substituted
      1,2,4-triazole-5-thiones were synthesized. The structures of the compounds have
      been elucidated by UV, IR, 1H-NMR, 13C-NMR spectra and elemental analysis. The
      anti-inflammatory activities of the compounds were evaluated by carregeenan
      induced hind paw edema and air-pouch inflammation tests in mice. In carrageenan
      induced hind paw edema test, compounds 1a, 1d, 3d, 4a showed equivalent or higher
      activity compared to naproxen and phenylbutazone. In the air-pouch inflammatory
      model, compounds 1a, 1b, 1d, 2c, 3c, 3d, 4a and 4d showed marked anti
      inflammatory activity. The ED50 values of these compounds ranged between 24-36
      mg/kg. Side effects of the compounds on gastrointestinal system and kidneys were
      examined and none of the compound showed significant side effects.

PMID- 11455680
TI  - Antioxidant activity of DL omega-phenyl-amino acid octyl esters with anti
      inflammatory activity. Correlation of the structure with lipophilicity.
AB  - The antioxidant activities (in vitro) and the lipophilicity (as RM values) of 12
      DL-omega-phenyl-amino acid octyl esters with anti-inflammatory/analgesic
      activities were studied. The tested compounds were found to interact with 1,1
      diphenyl-2-picrylhydrazyl stable free radical (DPPH), whereas most of them were
      essentially inactive in other tests. DL-2-Amino-4-(4-aminophenyl)butyric acid
      octyl ester was found to be the most active. The anti-inflammatory activity does
      not seem to be connected with O2-. or HO. scavenging activity at least under the
      experimental conditions applied. However, the interaction with DPPH was found to
      be correlated with their anti-inflammatory activity. Between the lipophilicity
      and the anti-inflammatory activity only a poor relationship exists. For a
      subgroup of the derivatives of the phenyl glycine octyl ester (1-8) a significant
      correlation was found between the RM values and the calculated clog P
      lipophilicity.

PMID- 11455681
TI  - Etofenamate levels in human serum and synovial fluid following iontophoresis.
AB  - The absorption of etofenamate (CAS 30544-47-9, Rheumon gel) by iontophoresis in
      11 patients with low back pain and in 13 patients with synovitis of the knee was
      evaluated. During the 5-day treatment period, the test gel in a quantity
      corresponding to 100 mg etofenamate was applied to affected body regions every
      day by 20-min iontophoresis sessions. Two hours after the fifth application, the
      concentration of etofenamate in serum and synovial fluid (in patients who had
      knee joint iontophoresis) were measured by HPLC. Iontophoresis of etofenamate
      into the lumbar region as well as to the knee joint resulted in consistent serum
      levels: 219 +/- 136.3 micrograms/l and 191 +/- 84.6 micrograms/l, respectively.
      In patients with synovitis of the knee, the synovial level of etofenamate (368 +/
      109.2 micrograms/l) was almost twice as high than the serum concentration. The
      authors conclude that with topical application of etofenamate by iontophoresis
      the drug appears not only in the serum but also--with higher levels--in the
      synovial fluid.

PMID- 11455682
TI  - Absorption of calcium administered alone or in fixed combination with vitamin D
      to healthy volunteers.
AB  - Calcium supplementation is widely used in deficiency status and as an adjuvant in
      the treatment of osteoporosis. As usual with endogenous substances, the calcium
      absorption, distribution and elimination processes are strictly controlled by
      homeostatic equilibria. Free calcium ion is the most representative active
      fraction of the circulating ion. Ion excretion is controlled by a saturable
      tubular reabsorption process which leads to a renal threshold. Cumulative urinary
      excretion of calcium is the end-point of absorption, distribution and elimination
      processes, and is thus a good indicator of bioavailability. In order to increase
      the oral bioavailability of calcium, the ion is administered in association with
      vitamin D, which is known to enhance intestinal calcium absorption. The aim of
      this study was to evaluate the absorption of calcium administered alone and in
      fixed combination with cholecalciferol (vitamin D3, CAS 67-97-0). In accordance
      with the study protocol, calcium carbonate (CAS 471-34-1; 1500 mg = 600 mg as
      calcium ion) was administered as such (reference) and associated with
      cholecalciferol (400 IU) (test) for four days (2 doses/day) to 18 healthy male
      volunteers in a sequential pattern, namely reference followed by test. Urinary
      excretion of total calcium, and serum concentration of free and total calcium, 25
      OH-vitamin D3 and parathyroid hormone were carefully analysed the day before
      (baseline) and on the 4th day of dosing, with validated methods. The effect of
      cholecalciferol in promoting calcium absorption was clearly observed from urinary
      excretion of total calcium, which with the test treatment showed a 16.6% increase
      in excretion (p = 0.025) compared with the reference treatment. The mean
      excretion values on the 4th day, expressed in mg, were 238.85 and 204.83 with
      test and reference respectively. Moreover, the results demonstrated an increased
      serum concentration of both free and total calcium after dosing with test and
      reference by comparison with the baseline situation. The area under the serum
      concentration-time curve of total calcium increased from day -1 to day 4 from
      550.98 to 575.90 mg l-1 h with test and from 543.03 to 568.16 mg l-1 h with
      reference. Similarly, ionised calcium increased on day 4 with both the
      treatments. Parathyroid hormone showed the expected typical decreasing behaviour
      after dosing with the test and reference drugs. The results of this study suggest
      that calcium carbonate is absorbed through the intestine when administered either
      alone or in association with cholecalciferol. Cholecalciferol, however, showed
      the typical expected activity in promoting calcium absorption, which was evident
      from the cumulative urinary excretion of the ion. To the authors' knowledge, this
      study is the first published paper demonstrating the absorption and
      pharmacodynamic effect of short-term administration of vitamin D associated with
      calcium at the doses recommended for supplementation in a fixed-combination
      pharmaceutical product.

PMID- 11455683
TI  - In vivo susceptibility of Mycobacterium ulcerans to KRM-1648, a new
      benzoxazinorifamycin, in comparison with rifampicin. Anti-mycobacterial activity
      of KRM-1648.
AB  - The antibacterial effects of a new benzoxazinorifamycin, KRM-1648 (3'-hydroxy-5'
      (4-isobutyl-1-piperazinyl, CAS 129791-92-0), against Mycobacterium ulcerans were
      evaluated in vivo in mouse foot pads, and the results were compared against those
      obtained with rifampicin (rifampin, CAS 13292-46-1). When mice were fed with the
      drugs from the day of footpad inoculations, KRM-1648, at concentrations of 0.001%
      and higher, mixed in mouse food, was effective in inhibiting the growth of M.
      ulcerans in the foot pads, and the effects were bactericidal. Effects of KRM-1648
      at 0.0005% were bacteriostatic. Similar results were obtained with rifampicin,
      but only at concentrations of 0.008% and above. In established infection, i.e.,
      when M. ulcerans were growing actively in footpads, bactericidal effects were
      observed with KRM-1648 at concentrations of 0.002% and above; to obtain similar
      results with rifampicin, the minimum dose was 0.032%. Thus, the results suggest
      the superiority of KRM-1648 over rifampicin in the treatment of M. ulcerans
      infection. The possibility of using KRM-1648 in combination with other
      antimycobacterial agents is discussed.

PMID- 11455684
TI  - Nematocidal activity of natural polyphenols from bryophytes and their
      derivatives.
AB  - The nematocidal in vitro activity of three natural perotetins (phenolic
      bisbibenzyiethers) and eleven diphenyl ethers used as synthetic precursors has
      been assayed using two different experimental models, Caenorhabditis elegans and
      Nippostrongylus brasiliensis. Nine compounds showed some activity against C.
      elegans and nine against N. brasiliensis. For the former model, three compounds
      displayed an activity similar to that of the standards, whereas for N.
      brasiliensis none of the tested compounds was as active as the standards. From
      the in vitro results, five compounds (3, 4, 8, 9, 13) could be selected as lead
      compounds to continue the search for improved activity.

PMID- 11455685
TI  - Improving natural principles with genetic engineering: TNK-tissue plasminogen
      activator.
AB  - The fibrinolytic system plays an important role in the physiological maintenance
      of blood flow and the dissolution of thrombi. Administration of fibrinolytic
      agents in indications such as myocardial infarction, pulmonary embolism, deep
      vein thrombosis or stroke, therefore, offers a rational means to dissolve
      pathological thrombi and restore vascular patency. The functional domains of the
      physiological tissue plasminogen activator (t-PA) provide fibrin specificity and
      serine protease activity for plasminogen cleavage and binding to liver receptors
      which gives the molecule a short half-life. In order to combat acute
      thromboembolic events such as myocardial infarction, the structure of the natural
      t-PA molecule was genetically modified to prolong its half-life, to increase its
      fibrin-specificity and to improve its resistance to plasminogen activator
      inhibitor. These features of TNK-t-PA allow bolus administration in emergency
      situations, early reperfusion of the blood vessel and a low rate of bleeding
      complications, thus improving the overall benefit to patients.

PMID- 11455686
TI  - [Subacute combined degeneration of the spinal cord: easy diagnosis, effective
      treatment].
AB  - Four patients, three women aged 49, 47 and 74 years, and a man aged 64 years,
      presented with progressive sensory deficit, pyramidal tract symptoms and postural
      instability. Tests revealed megaloblastic anaemia and low vitamin B12 levels. Two
      of the female patients had undergone gynaecological surgery with nitrous oxide
      anaesthesia, and the male patient had undergone a gastric resection. Subacute
      combined degeneration of the spinal cord is a neurological disease based on
      vitamin B12 deficiency. It involves the posterior and lateral columns of the
      spinal cord, and sometimes the peripheral nerves, the optic nerve or the brain.
      An MRI scan of the cervical cord revealed abnormalities for three of the four
      patients. Following parenteral supplementation of vitamin B12, the symptoms and
      the MRI abnormalities either disappeared or significantly improved. Vitamin B12
      deficiency can cause subacute combined degeneration of the cord by interfering
      with myelin synthesis. As vitamin B12 deficiency is caused by malabsorption in
      the gastrointestinal tract, oral supplementation is insufficient. It is essential
      to recognise this treatable disease at an early stage, and not to reject the
      possible diagnosis if the MRI findings are abnormal. Simple blood tests can lead
      to the diagnosis and to effective treatment.

PMID- 11455687
TI  - [Use of genetics in the Dutch health care system; a memorandum from the Dutch
      Minister of Health, Welfare and Sports to the Dutch Parliament].
AB  - In the memorandum entitled 'The application of genetics in health care', which
      was sent to the Dutch Parliament in December 2000, the Minister of Health,
      Welfare and Sport responded to four proposals she had received from the Health
      Council of the Netherlands during the previous three years. These proposals
      included reports on in vitro fertilisation, DNA diagnostics, clinical genetic
      testing and genetic counselling, and pharmacogenetics. Legal aspects dominate the
      section on the consumer's/patient's position: detailed legal guidelines are
      provided for difficult family-related issues in genetic counselling. For genetic
      counselling and clinical genetic testing, permission from the Minister of Health
      is still required. Criteria have been provided for the public funding of these
      activities in the shorter term. Clinical geneticists have been asked to develop
      guidelines for a number of clinical situations, which include predictive genetic
      testing and genetic testing in children. Moreover both medical and laboratory
      professionals have already initiated a number of self-regulatory measures. The
      Minister has adopted most of the proposals received, which means that for the
      foreseeable future, there is a clearly regulated framework for the responsible
      use of genetics within the Dutch healthcare system.

PMID- 11455688
TI  - [Results from the 'Ethiopia-Netherlands AIDS Research Project'; 1995-2000].
AB  - Since 1995 the 'Ethiopia-Netherlands aids research project' (ENARP) has been up
      and running in Addis Ababa, Ethiopia. Several surveys point towards an HIV
      seroprevalence of approximately 15% amongst adult Ethiopians in the capital city.
      Prospective cohort studies initiated since early 1997 indicate that healthy, HIV
      negative Ethiopians have lower CD4+ T-cell counts compared to the Dutch
      population and in addition they have chronically activated immune systems,
      possibly as a result of the highly prevalent intestinal parasitic infections as
      well as other infections. HIV positive Ethiopians are mainly infected with HIV-1
      subtype C, which can be subdivided in 2 subtypes, both of which entered Ethiopia
      in the early 1980's. There are considerable differences between Ethiopians and
      Dutch in terms of biomedical parameters relevant for HIV infection progression;
      these justify further efforts in future scientific research. The emphasis for
      this should be on robust and applicable laboratory methods, research in the field
      of HIV vaccine trials and information transfer to the various partners combating
      HIV infection/aids in Ethiopia.

PMID- 11455689
TI  - [AIDS vaccines: promises and reality].
AB  - Aids particularly affects people in developing countries, for whom the current
      forms of effective anti-retroviral therapy are both inaccessible and
      unaffordable. Just like smallpox in the past, the global aids epidemic can only
      be halted with a vaccine. It is estimated that the first generation aids vaccines
      will become available in about 10 to 15 years time. There is a sizeable chance
      that these vaccines will provide a certain degree of protection against aids and
      the spread of HIV. Yet in the short term, there is little chance of a vaccine
      which protects against infection from the HIV virus. The most important reason
      for this is that it has yet to be discovered how a vaccine can elicit antibodies
      which neutralise primary HIV isolates. The majority, if not all, first generation
      aids vaccines are expected to protect against aids on the basis of virus-specific
      T-cell immunity. The Netherlands has a key role in the aids vaccine programmes of
      the European Union (Eurovac) and is making important contributions to the
      International AIDS Vaccine Initiative.

PMID- 11455690
TI  - [From gene to disease; retinoblastoma and the RB1 gene].
AB  - Retinoblastoma is caused by mutations in the RB1 gene. The penetrance is 95%, as
      in approximately 5% of the mutation carriers, no second somatic mutation occurs
      in one of their retina cells during embryonic development. Molecular diagnosis is
      performed by a complete scanning of the RB1 coding sequence which includes
      flanking intronic sequences. Approximately 85% of pathogenic mutations can be
      identified.

PMID- 11455691
TI  - [Diagnostic image(44). Sheep tick (Ixodes ricinus)].
AB  - A thoracic skin tag was removed in a woman aged 69 years. Macroscopical and
      microscopical examination revealed a castor bean tick (Ixodes ricinus).

PMID- 11455692
TI  - [Hospital infections and risk factors in the intensive care units of 16 Dutch
      hospitals, results of surveillance of quality assurance indicators].
AB  - OBJECTIVE: To gain insight into the incidence of nosocomial infections and
      associated risk factors in Intensive Care Units (ICUs). DESIGN: Prospective.
      METHOD: From July 1997 to December 1999, standardised surveillance of nosocomial
      infections was implemented in ICUs in 16 hospitals in the Netherlands.
      Surveillance was performed in patients with an ICU stay of > or = 48 hrs; data
      were collected from admission until discharge from ICU. Data-collection included
      demographic data and patient- and treatment-related risk factors. The data were
      aggregated in a national database. RESULTS: In the research period, hospitals
      sent good quality data for aggregation in the national database on 2795 patients
      (61% male) and 27,922 ICU patient days. The median length of stay was six days,
      the median 'Acute physiology and chronic health evaluation' (APACHE) II score was
      17 and the median age was 67 years. A total number of 749 infected patients were
      found with 1,177 nosocomial infections (27% of patients, 42 infections/1000
      patient days), consisting of 43% pneumonia, 20% sepsis, 21% urinary tract
      infections, 16% other types of infections. Out of all the patients, 62% was on
      mechanical ventilation, 64% had a central venous line and 89% had a urinary
      catheter in situ. Selective decontamination of the gastrointestinal tract was
      used for 12% of the patients, and systemic antibiotics for 68%. Micro-organisms
      most frequently isolated were Pseudomonas aeruginosa in patients with pneumonia,
      Staphylococcus epidermidis in catheter-related bloodstream infections and
      Escherichia coli in patients with urinary tract infections. Large differences in
      device use and incidence of infections were observed between the ICUs.
      CONCLUSION: The aggregated data gave insight into the incidence of nosocomial
      infections and associated risk factors in ICUs. The data are meant as references
      to support decision- and policy-making in local infection control programs.

PMID- 11455693
TI  - [Implanted pacemakers in the Netherlands, 1984-1997; number, types and patient
      characteristics].
AB  - OBJECTIVE: To carry out a survey of the numbers of patients in the Netherlands
      who received a pacemaker in 1984-1997 and the types of pacemaker. DESIGN:
      Retrospective, descriptive. METHOD: Information on pacemaker patients and
      pacemakers in the Netherlands during the years 1984-1997 was obtained from the
      Dutch Pacemaker Patient Registration organisation and those in 15 other West
      European countries from the European Working Group on Cardiac Pacing. Both
      organisations use the European Pacemaker Identification Card. Demographic
      information was collected via Statistics Netherlands. RESULTS: In the
      Netherlands, 23 and 28 primo-implantations/100,000 inhabitants were carried out
      in 1984 and 1997 respectively. The increase was primarily due to a higher number
      of implants in people > 65 years of age. The 1997 implant figures were lower than
      the average in Western Europe (34/100,000). In 1997 there was no difference in
      gender, mean age at the time of first implant, indications and aetiology between
      the Netherlands and Western Europe. With respect to the choice of type of
      pacemaker implanted--VVI(R) or DDD(R)-in Western Europe, the Netherlands lay in
      the middle. Between 1984 and 1997, the number of Dutch centres with 1-25
      implants/year decreased while the number with 51-130 implants/year increased.
      CONCLUSION: In 1997 the number of primo-implantations at Dutch centres increased
      in comparison with 1984, but less than the West European average. Implants were
      increasingly performed in high-volume centres.

PMID- 11455694
TI  - [Cytomegalovirus infection: congenital or postnatally acquired? Importance of the
      Guthrie card].
AB  - A girl aged 4 weeks had persistent pulmonary hypertension of the newborn,
      haematological abnormalities and hepatosplenomegalia due to a cytomegalovirus
      (CMV) infection; thereafter she had a psychomotoric retardation. A girl aged 6
      months had psychomotoric retardation and microcephaly due to a CMV infection,
      with epilepsy and perception deafness. A polymerase chain reaction (PCR) for CMV
      DNA in the blood on the Guthrie card demonstrated retrospectively in both cases
      that the infection was congenital. A 4-month-old boy had parents who had both
      experienced a CMV infection around the birth of the child. The child was infected
      with CMV but the absence of CMV-DNA in the blood on the Guthrie card revealed
      that the infection was not congenital. Only 10% of infants with congenital CMV
      infection are symptomatic at birth; the prognosis is then poor. Up to 10-15% of
      the asymptomatic patients will develop neurological manifestations. For the
      diagnosis of congenital CMV infection virus isolation is required within 3 weeks
      after birth. However, when CMV infection is not considered during this period it
      is later still possible to diagnose congenital CMV infection with a PCR for CMV
      DNA in blood spots of Guthrie cards taken during the first week of life.

PMID- 11455695
TI  - [Ethiopia-Netherlands AIDS research project].
AB  - The 'Ethiopia-Netherlands AIDS Research Project' (ENARP), started in 1994, is a
      long-term collaboration between AIDS researchers in Amsterdam and the Ethiopian
      Health and Nutrition Research Institute in Addis Ababa. The ENARP's primary
      objectives include conducting studies on HIV and AIDS in Ethiopia, especially by
      means of some large-scale prospective cohort studies, training Ethiopian
      scientists in PhD programmes in epidemiology, immunology and virology and
      establishing a reference laboratory for HIV and AIDS in Ethiopia and neighbouring
      countries. External funding for ENARP amounts to 32 million Dutch guilders for
      two periods of four years and is being provided by the Dutch Government. ENARP is
      the largest third world biomedical project supported by the Dutch Government. In
      2000 two Ethiopian students obtained their doctorates from the University of
      Amsterdam. Five new PhD students commenced their training in 1999. ENARP hopes to
      set up HIV-1 vaccine phase I and phase II trials in the near future.

PMID- 11455696
TI  - [Determination of cardiac troponins for diagnosis 'acute myocardial infarct'].

PMID- 11455697
TI  - Routine postoperative oxygen by facemask--is it necessary?

PMID- 11455698
TI  - Practice administration--a cost-effective option.

PMID- 11455699
TI  - Celecoxib--the debate rages on.

PMID- 11455700
TI  - Celecoxib-- the debate ranges on.

PMID- 11455701
TI  - Community attitudes to HIV/AIDS.

PMID- 11455702
TI  - HIV test for rapists 'a minefield'.

PMID- 11455703
TI  - Spending good money on thin air.

PMID- 11455704
TI  - Arthritis and dysmenorrhoea.

PMID- 11455705
TI  - Impact of AIDS on med students.

PMID- 11455706
TI  - The Access to Information Act: implications for doctors.

PMID- 11455707
TI  - Guide to income tax for private practitioners.

PMID- 11455708
TI  - Adherence to antiretroviral therapy--achievable in the South African context?

PMID- 11455709
TI  - Primary level after-hours health services for children--a look at the western
      Cape metropolitan region.

PMID- 11455710
TI  - Use of traditional medicines--towards a classification.

PMID- 11455711
TI  - Problems with disability assessment--the Australian experience.

PMID- 11455712
TI  - Setting the scene for SORDSA--the importance of occupational respiratory disease
      surveillance in South Africa.

PMID- 11455713
TI  - Bio-social profile and survey of women seeking termination of pregnancy at
      Pelonomi and national hospitals, Bloemfontein.

PMID- 11455714
TI  - Necrotising fasciitis in an HIV-1-infected infant.

PMID- 11455715
TI  - Occupational respiratory diseases in South Africa--results from SORDSA, 1997
      1999.
AB  - OBJECTIVES: To describe the nature and extent of work-related respiratory
      diseases reported to the national Surveillance of Work-related and Occupational
      Respiratory Diseases in South Africa (SORDSA) reporting scheme. The causative
      agents and industrial categories in which they occurred are also characterised.
      DESIGN: Voluntary monthly reporting of newly diagnosed cases by pulmonologists,
      occupational medicine practitioners and occupational health nurses. SETTING:
      Medical and occupational health referral centres in the nine provinces of South
      Africa. SUBJECTS: Cases were workers from non-mining industries or ex-miners,
      suffering from a newly diagnosed occupational respiratory disease, reported to
      SORDSA between October 1996 and December 1999. OUTCOME MEASURES: Frequencies of
      reported occupational respiratory disease by year, reporting source, province and
      sex. Frequencies of short- and long-latency diseases by industry and causative
      agent. RESULTS: There was incomplete reporting coverage of the nine provinces in
      the first 3 years. Reporting was most comprehensive from Gauteng, KwaZulu-Natal
      and the Western Cape. Diseases with long latency periods made up 76.2% of the
      cases. Pneumoconiosis, even in non-mining industries, was the most frequently
      reported disease, followed by inhalation accidents. Occupational asthma was the
      fourth most reported disease. Apart from the prominence of pneumoconiosis, the
      results obtained by SORDSA are similar to those from a British occupational lung
      disease surveillance scheme. This study showed that newly diagnosed cases of
      occupational lung disease occurred in many industries and were caused by a
      variety of agents. CONCLUSION: SORDSA has contributed insight into the nature,
      extent and distribution of occupational respiratory diseases in South Africa. It
      has also highlighted important causes of occupational respiratory diseases in
      South Africa, as well as hazardous industries. The data indicate that South
      Africa has a widespread occupational lung disease problem, and provide a platform
      for targeted prevention strategies.

PMID- 11455716
TI  - Occurrence and causes of occupational asthma in South Africa--results from
      SORDSA's Occupational Asthma Registry, 1997-1999.
AB  - OBJECTIVE: To present results for the first 3 years of the occupational asthma
      registry of the Surveillance of Work-related and Occupational Respiratory
      Diseases in South Africa (SORDSA) programme, ending December 1999. DESIGN:
      Surveillance was accomplished by collecting voluntary reports of occupational
      asthma cases from pulmonologists, occupational medicine practitioners and
      occupational health nurses. SETTING: Medical and occupational health referral
      centres in the nine provinces of South Africa. SUBJECTS: Patients diagnosed with
      new-onset occupational asthma with latency or irritant-induced asthma, reported
      to SORDSA during 1997-1999. OUTCOME MEASURES: Frequencies of cases, causative
      agents, industries causing exposure and diagnostic methods. Average annual
      incidence rates by province and by occupation. RESULTS: During this period 324
      cases of occupational asthma were reported. The average annual incidence rate of
      occupational asthma was estimated in the three best-reporting provinces, namely
      Gauteng, KwaZulu-Natal and the Western Cape, as 17.5 per million employed people
      annually. This rate was highest in the Western Cape (25.1 per million). Semi
      skilled operators had the highest incidence rate of 68.7 per million annually in
      the three provinces. Isocyanates and latex were the most common agents. Low
      molecular weight causative agents predominated (68.8%) over high molecular weight
      agents. Health care was the most frequently reported workplace for occupational
      asthma (OA) development. Serial peak flow testing was the method most often used
      for diagnosis. One-fifth of the cases were still occupationally exposed to the
      causative agent at time of diagnosis. CONCLUSION: Despite underreporting,
      SORDSA's estimate of the occupational asthma incidence rate was similar to that
      of the UK. SORDSA has also demonstrated that surveillance programmes in a
      developing country can provide useful information on which to base prevention
      activities.

PMID- 11455717
TI  - Does tutor subject-matter expertise influence student achievement in the problem
      based learning curriculum at UNITRA Medical School?
AB  - OBJECTIVE: To establish whether or not tutor subject-matter expertise influences
      student achievement in content-based examinations in the problem-based learning
      (PBL) curriculum at the University of Transkei (UNITRA) Medical School. DESIGN: A
      retrospective study of MB ChB III student achievement in end-of-block modified
      essay questions (MEQ) examinations in microbiology, pathology and pharmacology
      for the years 1994-1999, inclusive. Pooled scores from the expert-tutored groups
      were compared with those from the groups tutored by non-experts using analysis of
      variance (ANOVA) or t-test. Subject expert tutors were those with postgraduate
      specialisation in the given discipline. SETTING: The Medical School, Faculty of
      Health Sciences, UNITRA, Umtata. OUTCOME MEASURES: Whether pooled mean MEQ scores
      in end-of-block examinations for microbiology, pathology or pharmacology differ
      according to the subject-matter expertise of the tutor. RESULTS: There were no
      significant differences in mean scores obtained for pharmacology (51.1 +/- 0.6
      versus 52.6 +/- 0.7, P = 0.109) and pathology (49.8 +/- 0.6 versus 49.9 +/- 0.8,
      P = 0.919). The difference between the scores in microbiology was small (3
      percentage points) but statistically significant, with the groups tutored by
      microbiologists scoring higher than those tutored by pathologists or
      pharmacologists (54.1 +/- 1.0 versus 51.2 +/- 0.8, P = 0.032). CONCLUSIONS: These
      data demonstrating that in the UNITRA Medical School PBL curriculum tutor subject
      matter expertise has little or no influence on student achievement in the
      discrete areas of tutor expertise.

PMID- 11455718
TI  - Public-private health sector partnerships for STD control in South Africa-
      perspectives from the Hlabisa experience.

PMID- 11455719
TI  - Cortical lens opacities in the young patient--an indication for a lipogram?
AB  - AIM: To determine the characteristics and prevalence of lenticular opacification
      in patients with underlying dyslipidaemia. METHODS: Eighty patients of both
      genders and all ages (18-90 years) were enrolled in the trial if they met the
      inclusion criteria for dyslipidaemia. Patients were included if their fasting
      serum cholesterol and triglyceride concentrations were > 5.2 mmol/l and > 2.3
      mmol/l, respectively, when measured on three separate occasions over a 1-month
      period. Patients were excluded if they suffered from any condition known to cause
      or predispose them to elevated lipid levels or lenticular opacification.
      Lenticular changes were assessed by means of a slit-lamp through the fully
      dilated pupil and other physical signs were documented subsequent to thorough
      physical evaluation. RESULTS: In addition to the classic clinic signs of
      dyslipidaemia, 31% of patients had cortical lens opacities. Cortical opacities
      were twice as prevalent as Achilles tendon thickening (16.3%) in our study, the
      second most prevalent sign of elevated lipid levels. In the subgroup of patients
      aged under 50 years, 55% had lenticular opacities, predominantly cortical (80%).
      CONCLUSIONS: Cortical lens opacification was the most prevalent sign of
      dyslipidaemia and it occurred at a relatively young age in our trial population
      in those patients who were affected. Cortical lenticular opacification should be
      regarded as an indication for blood lipid profile evaluation.

PMID- 11455720
TI  - Large-cell neuroendocrine carcinoma of the uterine cervix--a clinicopathological
      study of five cases.
AB  - OBJECTIVE: The present study describes 5 cases of large-cell neuroendocrine
      carcinoma (LCNEC) of the uterine cervix, evaluating their clinical features and
      pathological profiles. METHODS: Clinical data were obtained from the patients'
      clinical files at the combined gynaecological-oncology unit of Johannesburg
      Hospital and the University of the Witwatersrand Medical School, Johannesburg,
      South Africa. A histopathological diagnosis was obtained after biopsy material
      from all 5 patients was examined microscopically and subjected to
      immunohistochemical staining with MNF116 (pankeratin) synaptophysin and
      chromagranin A, all of which are neuroendocrine markers. Two patients received
      pelvic radiotherapy only. None of the 5 patients in this series received
      chemotherapy or underwent surgery. RESULTS: All 5 patients were adult females,
      with an average age of 57.3 years. The majority were multiparous, with the most
      common presenting complaint being vaginal bleeding. Three of the 5 patients
      presented with advanced-stage cervical carcinoma, with evidence of metastases in
      2 of them. Treatment responses and long-term survival in our series proved to be
      disappointing as 3 of the 5 patients died in less than 6 months. On
      histopathological examination, all 5 tumours showed features of a high-grade
      poorly differentiated malignant neoplasm with ulceration and extensive tumour
      necrosis including trabecular and organoid growth patterns. All 5 neoplasms also
      showed strong immunoreactivity for MNF116, while their endocrine nature was
      confirmed by staining for synaptophysin in all cases. None of the tumours showed
      positive straining for chromagranin A. CONCLUSIONS: LCNECs are rare tumours and
      distinct from other neoplasms of the uterine cervix. The results of this study
      reaffirm the biologically aggressive nature of this uncommon tumour and its very
      unfavourable prognosis.

PMID- 11455721
TI  - [Effect of autolysis on histochemical examinations of the central nervous
      system].
AB  - The objective of the study was to explain the effect of autolysis on
      immunohistochemical detection of neurone-specific enolase (NSE), beta-amyloid
      protein precursor (beta-APP) and ubiquitine in cerebral tissue. The examination
      was made in 6 deceased subjects without mechanical injury of the CNS and 6
      subjects with a craniocerebral injury who survived from 6 hours to 3 days. In all
      deceased subjects the post-mortem examination was made within 24 hours after
      death. For immunohistochemical examination tissue excisions were taken from
      standard sites of the brain. The first tissue excisions were immersed into 10%
      formol after a post-mortem interval of 24 hours. The remaining tissue slices were
      subjected to autolysis at room temperature and gradually immersed into formol
      after 24-hour intervals, the longest post-mortem interval being 168 hours, i.e. 7
      days. For visualization of the linked primary antibody the biotin-streptavidin
      system labelled with alkaline phosphatase was selected. In the group of 6
      subjects who died after a craniocerebral injury in 4 instances axonal lesions
      were detected, i.e. axonal oedema or formation of retraction spheroids. The
      damaged axons were positive on examination with all investigated antibodies,
      whereby it was possible even after a 168-hour post-mortem interval to
      differentiate damaged and not damaged axons. In the group of 6 subjects without
      mechanical injury of the CNS in 5 instances axonal oedema was found, however, it
      was not positive with anti-NSE antibodies nor with anti-beta-APP. After the 24
      hour post-mortem interval in this group in 3 instances ubiquitine positivity was
      found in axons but already after a post-mortem interval exceeding 2 days the
      axons were ubiquitine positive in all 6 subjects. Lumpy deposits of this
      substance could be detected in axons also beyond axonal structures.

PMID- 11455722
TI  - [Epidemiologic study of fatal injuries autopsied at the Institute of Forensic
      Medicine of the 3rd Medical School of Charles University Hospital in Vinohrady,
      Prague, from 1996 to 1999].
AB  - In our study comprising 1010 persons who died as a result of injury death at the
      age of 15-97 years and were autopsied in the Institute of Department of Forensic
      Medicine of the 3rd Faculty of Medicine and University Hospital Kralovske
      Vinohrady, were 748 men and 262 women. 717 died at the site of injury and 293
      died from the consequences of the injury in hospital. The most frequent cause of
      injury death was unintentional deaths (56.14%), followed by suicide (26.83%),
      murder (12.48%) and occupational injuries (4.55%). Road traffic accidents
      accounted for 51% of unintentional injury deaths. The most frequent cause of
      death was traumatic shock (32.67%), followed by injuries of the brain and spinal
      cord (30.50%). Injuries affect most frequently the head (60.5%) and chest
      (56.9%). The presence of alcohol in blood was detected at 30.2% of deceased.

PMID- 11455723
TI  - [Determination of the D-and L-forms of aspartic acid in intervertebral disk
      tissue as an indicator of age].
AB  - Assessment of age according to racemization coefficient of aspartic acid in
      dentin is considered a reliable method. Proteins which are isolated from dentin
      are non-collagenous proteins or collagen. As collagen is one of the most frequent
      proteins in the human body, the question arises whether the D-form of aspartic
      acid can be assessed also in other tissues and the racemization coefficient used
      for assessment of age. In the submitted work the author assessed to use the
      racemization coefficient in the tissue of the intervertebral disk. A lyophilized
      portion of the annulus fibrosus was hydrolyzed and the amino acids of the
      hydrolysate were estimated after derivation by gas chromatography on a chiral
      capillary column. The values of the racemization coefficient indicate limited
      possibilities to assess age from thus prepared tissue.

PMID- 11455724
TI  - [Determination of D- and L- forms of aspartic acid in Achilles tendon tissue as
      an indicator of age].
AB  - The presence of the D-form of aspartic acid was detected in collagen of dentin
      and the intervertebral disk before and assessment of its racemization coefficient
      was used for assessment of the age of subjects. Another tissue formed almost
      solely by collagen type I are tendons. Tendon tissue was not investigated so far
      with regard to the racemization coefficient and therefore the authors assessed
      the D-form of aspartic acid in the Achilles tendon. They used lyophilized tendon
      excisions which were hydrolyzed. Amino acids in the hydrolysate were derived to N
      TFA isopropyl esters which were assessed by gas chromatography on a chiral
      capillary column. In all samples the D-form of aspartic acid was detected. The
      values of the racemization coefficient suggest the possible use of thus processed
      tissue with certain limitations.

PMID- 11455725
TI  - [Position of the Czech Society of Forensic Medicine and Forensic Toxicology on
      evaluation of the effect of addictive substances other than alcohol on drivers
      (drugs)].

PMID- 11455726
TI  - Cohabiting couples in Great Britain: accommodation sharing, tenure and property
      ownership.
AB  - This article first considers some information from a pilot survey to test
      questions on past cohabiting unions which did not lead to marriage: when they
      started and finished; the reason why the couple stopped living together (either
      because the relationship ended, or because they stopped sharing the same
      accommodation, or both), and the corresponding durations. The article also
      analyses the key characteristics and immediate past accommodation history of
      couples who are currently cohabiting. In particular, patterns of tenure, property
      ownership and length of time cohabiting are explored--from a family law
      perspective.

PMID- 11455727
TI  - United Kingdom population trends in the 21st century.
AB  - This article considers the likely trends in population size, age structure and
      potential support ratios in the United Kingdom over the coming century. The
      extent to which these trends could be modified by changes in fertility or
      migration levels is examined. The findings of a recent United Nations report on
      'Replacement Migration' are also considered in the light of the Government
      Actuary's official population projections for the United Kingdom' together with
      new projection scenarios prepared specially for this article.

PMID- 11455728
TI  - Cohabitation in Great Britain: past, present and future trends--and attitudes.
AB  - As an introduction to the historical trends in cohabitation over the last quarter
      century, the article assesses the available evidence on changing attitudes-
      relating them to the changing patterns in the proportions cohabiting and
      premaritally cohabiting. Using data primarily from the General Household Survey
      (GHS) the article then traces the growth in cohabitation, and pre-marital
      cohabitation, and examines the differentials in cohabitation by age, marital
      status and sex. The proportions of women who cohabited pre-maritally before their
      first and second marriages are found to have grown substantially since the late
      1960s, to around 75 per cent and 85 per cent, respectively for marriages in the
      mid-1990s. Amongst those cohabiting at the time of interview, the length of time
      cohabiting has increased over the last 15 years, especially for single men and
      women. The duration of time women have been pre-maritally cohabiting before their
      first marriage has also increased over the same period--and their ages at the
      start of pre-marital cohabitation have become consistently older since the mid
      1960s. The possible future growth in the proportions and numbers cohabiting is
      also considered--and some of the implications discussed.

PMID- 11455729
TI  - Policy responses to population ageing and population decline in the United
      Kingdom.
AB  - This article is adapted from a paper given by the author at an expert group
      meeting convened by the Population Division of the United Nations in New York in
      October 2000 which considered 'policy responses to population ageing and decline'
      in selected countries.

PMID- 11455731
TI  - Intensive care medicine in Singapore: challenges in a new era.

PMID- 11455730
TI  - Evolution of intensive care medicine in Singapore.

PMID- 11455732
TI  - Alternate modes of financing health care technology.

PMID- 11455733
TI  - Perioperative treatment with bactericidal/permeability-increasing protein
      (rBPI21) in major liver surgery: a concise summary.
AB  - INTRODUCTION: Major hepatic resections are still associated with considerable
      morbidity. Gut-derived bacteria and bacterial endotoxin are considered to play a
      central role in the pathophysiology of complications. Experimental studies
      suggest that bactericidal/permeability-increasing protein (BPI), which has both
      antibacterial and endotoxin-neutralising properties, can reduce postoperative
      complications. MATERIAL AND METHODS: A phase II, double-blind, placebo
      controlled, multicentre, dose escalation trial was conducted in patients
      undergoing major liver resection, and clinical outcome, infectious complications,
      plasma amino acid patterns, coagulation and fibrinolytic cascade systems and
      neutrophil functions were compared between the two treatment groups and an extra
      group of patients undergoing major abdominal non-hepatic surgery. RESULTS: Drug
      administration in this patient group was safe, and resulted in a significant
      reduction of infectious complications. Furthermore, beneficial effects were found
      in the postoperative amino acid ratio and fibrinolytic cascades, and rBPI21
      preserved leukocyte functions. CONCLUSION: Administration of rBPI21 in patients
      undergoing major liver resection is well tolerated and results in improvement of
      both clinical and biochemical parameters.

PMID- 11455734
TI  - The role of early tracheostomy in critically ill neurosurgical patients.
AB  - OBJECTIVE: To determine the value of early tracheostomy (within 7 days) in
      ventilated neurosurgical patients. METHODS: Retrospective review of intubated
      patients in the neurosurgical intensive care unit (NICU) who underwent elective
      open tracheostomies for prolonged ventilation. RESULTS: Thirty patients over a 2
      year period were analysed. There were 19 males and 11 females, mean age 53.9 +/-
      18.1 years (range 14 to 89), and mean Glasgow Coma Scale (GCS) score on admission
      7.1 +/- 3.8 (range 3 to 15). The underlying disease aetiology was cerebrovascular
      disease in 53% of patients, head trauma in 33% and tumour or infection in 13%.
      Tracheostomy was performed after a mean period of 8.5 +/- 3.5 days (range 2 to
      18), with patients requiring ventilation for a mean duration of 13.5 +/- 6.3 days
      (range 3 to 31). Complications were minimal; 1 wound infection (3.3%) and 4 tube
      obstructions (13.3%). Patients who underwent elective early tracheostomy (Group 1
      = within 7 days) had poorer GCS on admission (6.3 +/- 2.9 versus 7.7 +/- 4.3 in
      Group 2, P = 0.271). Tracheostomy was performed after a mean of 5.3 +/- 1.7 days
      in Group I vs. 10.6 +/- 2.7 days in Group 2. Group 1 patients had faster recovery
      from nosocomial pneumonia (12.3 +/- 6.2 versus 17.9 +/- 12.5 days, P = 0.168),
      shorter duration of ventilation (9.8 +/- 5.9 versus 16.0 +/- 5.4 days, P =
      0.007), and reduced incidence of multibacterial tracheobronchial colonisation
      (42% versus 72%, P = 0.098). The most prevalent organisms were Acinetobacter
      baumanii (43.3%), Pseudomonas (40%), methicillin-resistant Staphylococcus aureus
      (MRSA) (33%), Klebsiella (30%) and Staphylococcus aureus (26.7%). CONCLUSION:
      Early tracheostomy in selected neurosurgical patients with poor GCS scores was
      associated with reduced incidence of tracheobronchial colonisation by multiple
      pathogens, improvement in chest infections, and rapid weaning from ventilatory
      support.

PMID- 11455735
TI  - Effect of different endotracheal suctioning systems on cardiorespiratory
      parameters of ventilated patients.
AB  - INTRODUCTION: We conducted this prospective randomised cross-over study to
      evaluate the effect of closed system (CS) versus open system (OS) endotracheal
      suctioning on heart rate (HR), mean arterial pressure (MAP), respiratory rate
      (RR), oxygen saturation (SpO2) and electrocardiogram (ECG) rhythm of patients on
      mechanical ventilation. MATERIALS AND METHODS: Fourteen adult patients were
      randomly allocated to receive either CS or OS suctioning in the first instance.
      For the subsequent suctioning, they were crossed over to the alternate suctioning
      system. The various cardiorespiratory parameters were recorded at BL1 (baseline
      1), S1 (first suction pass), BL2 (baseline 2, i.e. immediately post first suction
      pass), S2 (second suction pass), T2 (2 minutes post suction) and T5 (5 minutes
      post suction). RESULTS: Compared to CS, OS suctioning was found to result in
      higher HR at S1 (P < or = 0.05) and S2 (P < or = 0.05); higher MAP at BL2 (P < or
      = 0.05); lower SpO2 at BL2 (P < or = 0.01) and S2 (P < or = 0.01). There was no
      significant difference in RR between the two suctioning systems. OS suctioning
      was also noted to result in a significantly higher incidence of arrhythmia (P < =
      or 0.05). CONCLUSION: Our study shows that OS suctioning results in more adverse
      changes in cardiorespiratory parameters compared to CS suctioning.

PMID- 11455736
TI  - Abdominal complications after cardiac surgery.
AB  - OBJECTIVE: Abdominal complications after cardiac surgery are associated with a
      high mortality rate. Due to the absence of early specific clinical signs,
      diagnosis is often delayed. The present study seeks to determine predictive risk
      factors for subsequent gastrointestinal complications after cardiosurgical
      procedures. METHODS: Within 12 months, all patients (n = 1,116) who had undergone
      open heart surgery with cardiopulmonary bypass at our institution were studied
      for abdominal complications. To determine predictive factors, all case histories
      of the patients were analysed. RESULTS: Abdominal complications occurred in 23
      (2.1%) patients during the postoperative intensive care unit (ICU) stay, ten of
      whom had to undergo subsequent abdominal surgery. Of these 23 patients, 20 died.
      Early complications occurred most likely on postoperative days 6 and 7,
      consisting of bowel ischaemia or hepatic failure. Late complications consisted of
      gastrointestinal bleeding, pseudomembraneous colitis, cholecystitis and septic
      rupture of a spleen. The relative risk for abdominal complications after
      cardiopulmonary bypass was highly increased in association with a cardiac index
      less than 2.0 l/min-1/(m2)-1 (22.1-fold), postoperative onset of atrial
      fibrillation (16.6-fold), emergency surgery (10.7-fold), need for vasopressors
      (10.1-fold), need for intra-aortic balloon counterpulsation (8.6-fold), and the
      need for re-exploration within the first 24 hours (8.4-fold). All patients with
      necrotic bowel disease had elevated serum lactate levels. Furthermore, both
      cardiopulmonary bypass and aortic clamping times were significantly prolonged in
      patients who developed gastrointestinal complications. CONCLUSIONS: A number of
      predictive factors has been described to contribute to the development of
      abdominal complications subsequently after cardiac surgery on cardiopulmonary
      bypass. Knowledge of these factors may lead to earlier identification of patients
      at increased risk and may allow for more efficient and earlier interventions.

PMID- 11455737
TI  - Obstetric admissions to the intensive therapy unit of a tertiary care
      institution.
AB  - INTRODUCTION: Between 0.1% and 0.9% of women develop pregnancy complications
      which require admission to an intensive therapy unit. The aim of this study was
      to review all obstetric admissions to the intensive therapy unit at the KK
      Women's and Children's Hospital from 1998 to 1999 with respect to indications for
      admission, interventions employed and clinical outcome. METHOD: The medical
      records of all obstetric patients admitted to the intensive therapy unit during
      the 2-year period were analysed retrospectively. Subjects were included if they
      were admitted during pregnancy up to 42 days postpartum. RESULTS: There were
      31,725 deliveries in our hospital during the study period of which there were 239
      admissions to the intensive therapy unit. Of these, 42% were Malays, 41% Chinese,
      12% Indians and 5% other races. 65% stayed 1 day, 24% 2 days, 7% 3 days and 4%
      more than 3 days. The patients' ages ranged from 18 to 44 years. The indications
      for admission were hypertension (50%), haemorrhage (24%), respiratory
      insufficiency (10%), neurological problems (11%) and sepsis (3%). Intervention
      wise, 43% of patients required vasoactive infusions, 35% had arterial line
      placement, 22% central venous pressure monitoring, 21% ventilatory support and 2%
      pulmonary artery catheter placement. The maternal mortality and stillbirth rates
      were 1.3% and 3.7% of intensive therapy unit admissions, respectively.
      CONCLUSION: The admission rate to the intensive therapy unit in our institution
      was 0.73% of all deliveries during the 2-year study period. Hypertensive disease
      and haemorrhage were the predominant admitting diagnoses.

PMID- 11455738
TI  - An audit of patients with rheumatic disease requiring medical intensive care.
AB  - INTRODUCTION: Medical intensive care for patients with rheumatic disease is
      usually complicated by significant morbidity and mortality. The aims of this
      study were to examine the reasons for admission, the outcomes of these patients
      and the possible prognostic factors in an Asian cohort. MATERIALS AND METHODS:
      This was a retrospective study of the case records of 29 admissions to the
      medical intensive care unit (MICU) of Tan Tock Seng Hospital (TTSH) from August
      1999 to August 2000. RESULTS: There were 28 patients admitted, of whom 1 had a
      repeat admission. The majority of these patients were young (mean age 38.9 +/-
      16.3 years) and 71.4% were females. Twenty patients (71.4%) had systemic lupus
      erythematosus (SLE). The main reasons for admission were infection/sepsis
      syndrome (n = 18), hypotension (n = 16) and acute respiratory failure (n = 14).
      The observed in-hospital mortality was 64.3%, which was higher than the predicted
      risk of hospital death of 47.3%. Infection contributed to 55.6% of deaths. The
      patients who died had a longer mean duration of the rheumatic disease, higher
      APACHE II scores, higher rates of hypertension and hyperlipidaemia, higher doses
      of steroid and immunosuppressive therapy and more organ failures. Renal failure
      and acute respiratory distress syndrome were the two most common organ failures
      in patients who died. CONCLUSION: Many of our critically-ill patients with
      rheumatic disease were young females with good functional status. Despite the
      high mortality, they should be aggressively treated because infection and acute
      respiratory failure are potentially reversible.

PMID- 11455739
TI  - The practice of foregoing life support in the critically ill "old old": a
      Singapore perspective.
AB  - OBJECTIVE: To study the practice of foregoing life support (FLS) therapy between
      the young old and the old old. PATIENTS AND METHODS: This is a retrospective case
      control study of case records for FLS events and illness characteristics among
      young old patients (55 to 74 years) and old old patients (75 years and older)
      admitted in 1998 to the medical intensive care unit (MICU). RESULTS: Fifty-seven
      out of 282 patients (20.2%) had FLS orders. There was no statistical difference
      in the use of FLS orders between the young old and the old old (17.1% versus
      27.0%, P = 0.06), although there was a trend towards more frequent use in the old
      old. APACHE II(M) score (APACHE II score calculated without inclusion of points
      for age) and a high risk admitting diagnosis correctly predicted 80.5% of FLS
      events. A higher frequency of relatives of old old patients (20.8%) initiated FLS
      discussions compared to the young old (6%). In both groups, the child was the
      main surrogate decision-maker (n = 38, 66.7%). Medical futility/poor prognosis
      was the most common reason for FLS, accounting for 86.9% of patients. Withdrawing
      or withholding of mechanical ventilation was the most common mechanism (66.7%) of
      FLS. The majority (61.4%) died in the MICU after FLS. Of the 57 patients who had
      FLS orders, 1 young old and 3 old old survived till hospital discharge.
      CONCLUSION: Illness severity, as reflected by the APACHE II(M) score and the
      presence of a high-risk diagnosis, rather than age, predicted FLS orders.

PMID- 11455740
TI  - Retinol palmitate counteracts oxidative injury during experimental septic shock.
AB  - INTRODUCTION: Retinols seem to be of clinical importance in ameliorating the
      clinical consequences of septic shock. These beneficial effects of retinols are
      suggested to be due to an antioxidant property. The present study was undertaken
      in order to confirm or rule out such an effect of retinol palmitate (RP) in
      experimental septic shock by measuring F2-isoprostanes and a major prostaglandin
      F2 alpha metabolite as indicators of oxidative injury and inflammatory response,
      respectively. MATERIALS AND METHODS: Fourteen anaesthetised pigs were randomly
      given an injection of RP (2.300 IU x kg-1) or the corresponding volume of
      vehicle. All pigs received a continuous infusion of E. coli endotoxin (10
      micrograms x kg-1 x h-1). Blood samples were analysed for lipid peroxidation
      products (8-iso-PGF2 alpha), indicating free radical induced oxidative injury and
      15-keto-dihydro-PGF2 alpha indicating cyclooxygenase-mediated inflammatory
      response). RESULTS: Significantly elevated levels of 8-iso-PGF2 alpha were seen
      at 3, 5 and 6 hours of endotoxaemia in the vehicle + endotoxin group as compared
      to RP + endotoxin group. Endotoxin induced cyclooxygenase-mediated inflammatory
      response was not affected by RP. CONCLUSIONS: This study is the first one to show
      that RP counteracts oxidative injury rather than inflammatory response in
      experimental septic shock. These results may be of importance for the
      understanding of some beneficial effects of RP during endotoxaemia (i.e. improved
      systemic haemodynamics and reduced serum levels of endotoxin). Our results may
      explain the therapeutic effects of nutrients rich in caroten/retinols used in
      some clinical studies.

PMID- 11455741
TI  - Nitric oxide production by human peripheral blood mononuclear cells.
AB  - INTRODUCTION: There are conflicting data on the ability of human mononuclear
      cells to produce nitric oxide (NO). We investigated nitric oxide production from
      peripheral blood mononuclear cells (PBMs) by using a new sensitive fluorescent
      indicator. MATERIALS AND METHODS: PBMs from healthy volunteers were collected,
      plated in 96-well microplates, and loaded with the fluorescent nitric oxide
      probe, 4,5-diaminofluorescein diacetate (DAF-2DA). Experiments were performed in
      normal control and endotoxin-stimulated PBMs, with and without exogenous L
      arginine. The exogenous nitric oxide donor S-nitroso-N-acetyl-penicillamine
      (SNAP) was used as a positive control. Fluorescence intensity was measured with a
      fluorescence microplate reader. RESULTS: Nitric oxide production by human PBMs
      can be demonstrated by the use of the fluorescent indicator, DAF-2DA, in both
      control and endotoxin-stimulated conditions. Nitric oxide production was
      independent of the concentration of exogenous L-arginine. The addition of
      endotoxin did not change nitric oxide production. PBMs treated with SNAP showed a
      concentration dependent increase in fluorescence. Nitric oxide production over 5
      hours was constant and identical in both control and stimulated groups.
      CONCLUSION: This fluorescent indicator technique is useful for the study of NO
      production by human PBMs. Nitric oxide production by PBMs was independent of
      exogenous L-arginine concentration and was not affected by endotoxin.

PMID- 11455742
TI  - Simulation-based training at the University of Pittsburgh.
AB  - The following article reviews the experience of using human simulators for
      medical education at the University of Pittsburgh in the Department of
      Anesthesiology and Critical Care Medicine. The intent of the authors is to
      provide the reader with an overview of 1) what human simulators can do, 2) the
      components of a simulation training facility, 3) some of the economic
      considerations in operating a simulation training facility, and 4) how this
      centre is made use of.

PMID- 11455743
TI  - Limitation of life support in the critically ill: the Hong Kong perspective.
AB  - INTRODUCTION: Patients admitted to the intensive care unit (ICU) may not benefit
      from the life support provided and it may result in prolonged and unnecessary
      suffering. Limiting life-support therapy in this situation is an ethically
      acceptable practice in Western countries. Statements produced by professional
      bodies have been generally made from a Western perspective. Cultural influences,
      aspects of management and resource limitations may create differences, yet there
      is little information available on the ethical decision making processes involved
      in limitation of life support in Asian countries. This article reviews the
      processes involved in the limitation of life support in critically ill intensive
      care patients in the predominantly Chinese population of Hong Kong. METHODS:
      Direct and computerised search of locally available and international published
      research articles and opinions. RESULTS: Limitation of life-support therapy
      occurs in 23% to 61% of critically ill Chinese patients that die within the ICU
      which is comparable to figures presented in the Western literature. Relatives
      wish to be part of the decision making process when limitation of therapy is to
      be considered. A staff attitude of caring towards patient and family, a need for
      information from the doctor and staff, and competence in providing adequate
      treatment have been identified as important factors by relatives when limitation
      of life-support therapy was being discussed. CONCLUSIONS: Limitation of therapy
      in dying Chinese patients occurs in ICUs and, patients and relatives concur in
      95% of cases with medical decisions to limit therapy in these patients. The
      importance of communication as well as a desire to participate in the decision
      making process regarding limitation of therapy suggest similarities between
      Western and Asian expectations. More comprehensive data are required regarding
      end-of-life issues in the Asian context, especially in relation to the general
      population's perception as to the processes involved.

PMID- 11455744
TI  - Quality of life in long-term survivors of intensive care.
AB  - INTRODUCTION: Traditionally, outcome from intensive care has focused on
      mortality. The cost of intensive care and the limited resources devoted to
      patients who have a poor prognosis also raises questions about the utilisation of
      such resources. There is increasing pressure for outcome evaluation of intensive
      care to incorporate assessment of long-term survival and the quality of life in
      survivors. The principal objectives of this article were to examine current
      methods of assessing quality of life measures in critically ill patients
      surviving intensive care and to determine the quality of life of these survivors.
      METHODS: Direct and computerised search of published research articles. RESULTS:
      Measurement of quality of life after intensive care is not common practice. There
      is a lack of consensus concerning appropriate measuring instruments to be used
      and how best to interpret results. Despite the availability of general outcome
      tools and disease specific instruments, there is a paucity of studies in the
      literature which include assessments of quality of life following intensive care
      unit (ICU) care. Generic health indices suggest that the quality of life in ICU
      survivors is acceptable though in certain sub-groups, e.g. adult respiratory
      distress syndrome and sepsis, quality of life may be moderately impaired. ICU
      survivors appear to suffer less disability than chronic physical disease
      patients. CONCLUSIONS: Assessment of outcome after intensive care should include
      health related quality of life measurements. A unifying framework is required to
      enhance communication between clinicians, administrators and investigators of
      quality of life research and also to enable more rational and effective decision
      making at the bedside. Patients who survive intensive care appear to enjoy a
      reasonable standard of quality of life. While their health status may not be as
      good, subjectively patients find this acceptable.

PMID- 11455745
TI  - Anaemia in the critically ill--the optimal haematocrit.
AB  - INTRODUCTION: The optimal haematocrit for the critically ill patient is
      undetermined. METHODS: This review focuses on clinical and experimental papers
      regarding the aetiology and management of anaemia from the Medline database. Data
      from our intensive care unit (ICU) were also included. RESULTS: Anaemia may
      result from frequent blood sampling, gastrointestinal bleeding, surgical blood
      loss, impaired erythropoeitic response, and nutritional deficiencies of iron,
      vitamin B12 and folate. Available data on the minimum tolerated Hct are
      conflicting. There has been emphasis that transfusions should not be based on a
      single "trigger". Recent data suggest a linear relationship between Hct and
      cerebral oxygen delivery (DO2). There is evidence that anaemia increases the
      mortality, and the risk is higher in patients with cardiovascular disease.
      Conversely, transfusions are not without risks, which include transmission of
      infections, incompatibility reactions and immunomodulation. Restricting blood
      transfusion has been shown to result in lower 30-day mortality in certain patient
      groups. Minimising blood loss and nutritional support are important. Alternative
      strategies to transfusion include erythropoeitin and blood substitutes like cell
      free haemoglobin, perfluorocarbon emulsions and liposome-encapsulated Hb.
      Hyperbaric oxygen has also been tried. CONCLUSION: Oxygen consumption requires
      oxygen delivery. Haematocrit delivers oxygen. However, if oxygen delivery is not
      limited by haematocrit or is achieved by other means, then the concept of the
      optimal haematocrit is irrelevant. There are currently no guidelines for the
      management of anaemia in the critically ill.

PMID- 11455746
TI  - Advances in neurointensive care.
AB  - PURPOSE: To highlight recent advances in neurological and neurosurgical intensive
      care. DATA SOURCES: A MEDLINE search was conducted from January 1980 to August
      2000. Keywords included intensive care, head injury, subarachnoid haemorrhage,
      status epilepticus, myasthenic crisis, Guillain-Barre syndrome and stroke. All
      articles in English were considered for review. Additional articles were
      identified from the references of the retrieved articles and cross-referencing
      selected articles. DATA EXTRACTION: All clinical studies, review articles and
      abstracts were reviewed. DATA SYNTHESIS: Rapid advances in neurological and
      neurosurgical intensive care in the last decade have led to the development of
      specialised neurointensive care units with joint ventures between neurology and
      neurosurgery. Work in these units have contributed immensely to our understanding
      of the pathophysiology and management of acute brain injury. The principles of
      intensive care management include amelioration or reversal of brain injury and
      preservation of normal neural tissue. Treatment algorithms are possible with the
      aid of intense clinical and neurophysiologic monitoring. Ongoing clinical and
      basic science research may provide new treatment options for the intensivist in
      the acute phase of brain injury. CONCLUSION: Specialised neurointensive care
      units provide the best environment for the patient with acute brain injury.
      Outcome is frequently enhanced the clinicians skilled towards dealing with the
      whole spectrum of neurologic insults.

PMID- 11455747
TI  - Intra-abdominal hypertension--implications for the intensive care physician.
AB  - INTRODUCTION: Intra-abdominal hypertension is becoming increasingly recognised in
      intensive care patients. The objective of this paper was to review the modern
      published literature to establish a representative consensus view of the
      incidence, causes, pathophysiology, management and outcome of intra-abdominal
      hypertension. METHODS: A computerised MEDLINE search from 1966 to November 2000
      was conducted using the Medical Subject Heading and textwords "abdominal",
      "compartment syndromes", "intra-abdominal" and "hypertension" and "pressure". The
      references of recent articles were checked for additional relevant citations.
      Papers were independently assessed for relevance by authors SJR and GMJ using a
      data collection format. Data were assessed qualitatively and papers detailing
      physiologic variables, effects of decompression and outcome were abstracted in
      table form. CONCLUSIONS: Intra-abdominal hypertension exists when intra-abdominal
      pressure exceeds 10 to 12 mmHg as physiological aberrations are manifest above
      this pressure. Incidence is 5% to 40% in high-risk surgical patients.
      Pathophysiological changes caused by intra-abdominal hypertension include effects
      on the gastrointestinal, cardiovascular, renal, respiratory and central nervous
      systems. An association between intra-abdominal hypertension and subsequent
      multiple organ failure has been repeatedly shown, although causation remains
      unproven. Monitoring intra-abdominal pressure (IAP) by measuring urinary bladder
      pressure is easy and accurate. However, it is unclear what level of intra
      abdominal pressure requires intervention (decompression), or what length of time
      intra-abdominal hypertension can be tolerated before significant end organ damage
      occurs. In the absence of good outcome data, expert consensus is that an acute
      increase of IAP to above 20 to 25 mmHg and/or evidence of abdominal compartment
      syndrome warrants urgent decompression. While some progress has been made in
      describing and managing this clinical entity, further studies are needed to fully
      understand the clinical implications and confirm appropriate management of this
      condition.

PMID- 11455748
TI  - Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci:
      emerging problems and new prospects for management.
AB  - INTRODUCTION: Infections due to multidrug-resistant Gram-positive bacteria are a
      growing worldwide problem, particularly among seriously ill patients. A number of
      studies have demonstrated that patients infected with either methicillin
      resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE)
      are at higher risk for mortality and medical resource expenditures. METHODS: A
      non-systematic evidence-based review of linezolid, the first commercially
      available oxazolidinone, and quinupristin/dalfopristin, the first injectable
      streptogramin, for management of these multidrug-resistant infections was
      conducted. RESULTS: As infections due to VRE increase and vancomycin-insensitive
      MRSA emerge, vancomycin is becoming less effective for managing Gram-positive
      infections. Preclinical comparative studies demonstrated that linezolid and
      quinupristin/dalfopristin are highly effective in eradicating both susceptible
      and resistant staphylococci, streptococci, and enterococci. Clinical experience,
      including phase III and compassionate-use data, with these newer agents in the
      treatment of MRSA and VRE infections are discussed. CONCLUSIONS: The clinical
      experiences thus far with linezolid and quinupristin/dalfopristin for MRSA and
      VRE infections have demonstrated efficacy, making these agents important
      additions to the limited number of therapeutic alternatives for Gram-positive
      infections.

PMID- 11455749
TI  - Visual survey of cancer dissemination: classic patterns on helical CT of the neck
      and thorax.
AB  - Important sites of metastasis from intrathoracic and extrathoracic primary
      neoplasms are depicted on helical CT of the neck and thorax. This pictorial essay
      reviews several of these key sites of dissemination. For each, we illustrate the
      typical or classic appearance on helical CT and note the commonly associated
      primary malignancies.

PMID- 11455750
TI  - Imaging options.

PMID- 11455751
TI  - Rosacea skin care.

PMID- 11455752
TI  - Rosacea: a tiered approach to therapy.

PMID- 11455753
TI  - Systemic therapy for rosacea: focus on oral antibiotic therapy and safety.
AB  - Although potentially significant adverse reactions and drug interactions have
      been reported in association with erythromycin, oral tetracyclines, and
      trimethoprim-sulfamethoxazole, overall these agents are associated with excellent
      safety profiles, especially considering their widespread use over many years. It
      must be considered that when these antibiotics are used for the treatment of
      rosacea and also for acne vulgaris, their use is on a long-term basis rather than
      their typical short-course regimens for most infectious diseases. As a result,
      dermatologists prescribing these agents may feel assured that most patients will
      not encounter any significant problems, but they do need to be aware of potential
      adverse reactions to allow for early recognition and discontinuation of the
      offending drug when needed. Early recognition also allows for favorable
      management of adverse reactions. In addition, potentially significant drug
      interactions may be recognized by obtaining a thorough medical history and
      avoiding combinations of drugs that may interact unfavorably. Fortunately, there
      are several choices that allow us to individually select a treatment regimen that
      is optimal for the individual patient, allowing for effective control of rosacea.

PMID- 11455754
TI  - [Health counseling about alcoholic beverage consumption].
AB  - This paper reviews the scientific evidence on the relationship between
      consumption of alcoholic beverages and health, at the individual and population
      levels. This evidence is used to inform the health counselling on such
      consumption. We propose that during the individual clinical encounter, the
      counselling should be adapted to clinical characteristics of the patient (mainly
      age and cardiovascular risk), consider the patient preferences (because there are
      alternatives to alcohol for cardiovascular prevention for those who do not like
      alcohol), and prudent ('primum non nocere'). For the population, the advice
      should be: "if you consume alcohol, less is better".

PMID- 11455755
TI  - [Eco-pathologies: effect on public health and animal health].
AB  - This study emphasizes on pathologies which rates are increasing due to human
      activities that alter the environment such as industries, deforestacion, etc....
      This ecopathologies are different from those caused by occasional natural agents.
      On the contrary, the agents responsible for these pathologies include gases such
      as CO2, NO and SO, released to the atmosphere, metals such as mercury, cupper,
      plumb, cadmium and chrome, contaminating soil and water, and pathogens of protein
      nature, i.e. prions, extended through the utilisation of feed of animal origin in
      intensive farming.

PMID- 11455756
TI  - [Integrins and reproduction].
AB  - Integrins are glycoproteins of dimeric structure and promote the binding between
      the cytoplasm and the Intercellular Matrix System or ICM. Its mechanism of action
      is very diverse and also very complex in each case; but it is very interesting to
      note that its intervention in reproductive processes is of paramount interest.
      Integrins promote the penetration of the head of spermatozoon into the oocyte,
      cause the secretion of nutrient substances in the tubal mucosa and finally
      determine the formation of the "implantation window" in the endometrium. Further
      penetration of egg in the decidua and the formation of the placental trophoblast
      originate from the action of integrins. In certain pathologic situations as
      ectopic pregnancy or endometriosis, integrins play a primordial role. In the
      treatment of infertility and in the technology of IVF.

PMID- 11455757
TI  - [The truth and present uncertainty about mad cow disease].
AB  - A historical review is made about Spongiform Encephalopathies which affect both
      animals and man. This is the base for an epidemiological and predictive analysis
      of these type of diseases, especially Bovine Spongiform Encephalopathy (BSE) as a
      present health problem. The scientific certainties or truths, such as the prion
      theory (PrPc-PrPsc), the low natural infectivity of these group of diseases, the
      high dose of prions necessary to produce the experimental disease, the species
      barrier or specificity, the individual susceptibility due to genetic traits, and
      the low transmission efficiency by the oral route, compared to the parenteral
      route, agree with the epidemiological observations of human cases of the variant
      of the Creutzfeldt-Jakob disease (vCJD), which is 0.1 cases per million
      inhabitants and year. The present and future prediction of BSE should not be
      alarmist, taking into account the certainties that we know.

PMID- 11455758
TI  - ["De morbis qui in superficie corporis videntur" (St. Isidore of Seville, 621
      A.D.) the first dermatology text in Europe].
AB  - San Isidoro of Sevilla (562-636) was a learned Spaniard of the early Middle Ages.
      His principal work, the Etymologies, is an encyclopedic treatise which analyzes
      the origin and meaning of about 5,500 terms corresponding to the different
      knowledge of his era. Liber IV of the Etymologies is dedicated to Medicine, and
      one of his chapters, titled De morbis qui in superficie corporis videntur (The
      diseases that are seen on the skin surface), studies 32 terms corresponding to
      skin diseases, so that this chapter represents the first text dedicated
      specifically to Dermatology in Europe. At the same time, according to the general
      plan of the work that includes each term with its origin and its definition,
      Liber IV (De Medicina) would be the oldest medical terminology dictionary known.

PMID- 11455759
TI  - [Child abuse].
AB  - Aspects of interest with regard to childhood maltreatment are studied. Data (not
      published) of the "Instituto del Menor y la Familia de la Comunidad de Madrid"
      are reported from January 1999 to June 2.000: 200 cases of child neglect, 187
      cases of physical abuse, 143 cases of sexual abuse and 123 of psychological
      abuse. Risk factors, prediction, therapy and prevention of child maltreatment are
      also studied.

PMID- 11455760
TI  - [Epidemiology of the animal prion diseases].
AB  - The authors review the epidemiology of spongiform encephalitis, discussing the
      possible mechanism of appearance of the epidemic bovine spongiform encephalitis
      epidemic, leaving aside to another publication the epidemiology of the human
      spongiform encephalitis and its pathogeny.

PMID- 11455761
TI  - [Reflections on the ether].
AB  - In the first place, a history of physical aether is propounded, a history of that
      initially considered hypothetical substance which should fill empty space, and
      whose properties would vary depending on the scientific phenomenon and the
      temporal scientific context under consideration. Secondly, in the light of this
      history and from the present time, several reflections are made about the general
      problematics of Physics and Philosophy and some of their correlated traditional
      problems: The problem of space, the problem of empty space, the problem of
      matter, and, particularly, the problem of aether.

PMID- 11455762
TI  - [Profiles of youths in modern society and health risks].
AB  - The youngsters are clearly conditioned by the society where they live, though
      they may feel apart. These youngsters have benefited from more educative and
      material resources than generations before, and their vital and social itinerary
      will depend, in great part, from the behaviours and attitudes acquired during
      adolescence and youth. They have not been formed in austerity and determination.
      They mainly value the near and the present. Courses of action more determined by
      the emotional than by the rational. While tolerant, they have selfish traits with
      self-contradictions between end- and instrumental values (effort, dedication,
      compromise), and certain indifference for the religion. Finally, they are
      demonstrate solidarity in specific situations.

PMID- 11455763
TI  - [Bone lithiasis in the period of the Enlightenment: D.F.J.B. Trehet].
AB  - OBJECTIVE: To briefly describe the life and works of D.F.J.B. Trehet, a physician
      of the city of Rouen (France), who was the first to describe the "osseous points"
      in a renal calculus. Trehet has not been recognized or referenced for this
      original observation in the urological publications. METHODS: Trehet lived in the
      period of the Enlightenment and endured the upheavals of the French Revolution.
      Data gleaned from several sources have permitted and elaborate description of
      this French physician from both the social and professional perspectives.
      RESULTS: After completing his studies at the Hotel Dieu in Rouen, D.F.J.B. Trehet
      pursued his education at the School of Health in Paris. He read his doctorate's
      thesis at the Paris School of Medicine in 1803 and published his observation of a
      renal calculus "with osseous points" in 1812. Other studies by D.F.J.B. Trehet
      were also published in Le Journal de Medecine, Chirurgie et Pharmacie.
      CONCLUSIONS: D.F.J.B. Trehet should be recognized as the first to describe an
      osseous renal calculus.

PMID- 11455764
TI  - [Observational study of therapy compliance in the treatment of uncomplicated
      urinary tract infections of the urinary tract with 500 mg ciprofloxacin
      suspension].
AB  - OBJECTIVE: To evaluate patient compliance with 500 mg. ciprofloxacin oral
      suspension therapy for uncomplicated tract infections. METHOD: Open, non
      comparative, multicenter study of 87 patients of both sexes. Mean age was 67.5
      years. Duration of treatment ranged from 3 to 10 days. RESULTS: The degree of
      compliance with treatment was satisfactory in 82.7% of the cases. CONCLUSION: The
      characteristics of the 500 mg ciprofloxacin oral suspension (easy to take, easy
      to use, etc.) facilitate patient compliance with the treatment prescribed for
      uncomplicated urinary tract infections.

PMID- 11455765
TI  - [Incidence of high grade prostatic intraepithelial neoplasm in transrectal biopsy
      of the prostate].
AB  - OBJECTIVE: To analyze the incidence of high grade prostatic intraepithelial
      neoplasia (PIN) in the transrectal prostate biopsies of patients from the Urology
      department. METHODS: From 1995 to 1999, 2018 patients aged 46-92 years (mean 68
      +/- 10) had a transrectal biopsy. Thirty-six percent had a suspicious DRE and the
      mean serum PSA was 31.7 +/- 152.9 ng/ml. The anatomopathological diagnoses were:
      a) cancer, b) benign pathology, c) high grade PIN and d) glandular atypia.
      Statistical analysis using the chi square and Mann-Whitney tests was performed to
      compare the following variables: age, DRE, PSA, PSAf/PSAt ratio and the finding
      of a suspicious node on ultrasound. RESULTS: The incidence of high grade PIN in
      this series was 8% and the incidence of prostate cancer was 38.6%, PIN grade 3
      was diagnosed in 94 patients and PIN grade 2 in 67, and was associated with
      glandular atypia in 13 patients. Patients with prostate cancer were older and
      showed statistically significant higher PSA, percentage of suspicious DRE,
      sonographically suspicious nodes, and a lower PSAf/PSAt ratio than the other
      diagnoses (p < 0.001). Comparison of patients with high grade PIN and those with
      benign pathology showed no differences for age, DRE, PSA levels and PSAf/PSAt
      ratio. However, a significantly lower incidence of sonographically suspicious
      nodes was found (p < 0.001). CONCLUSIONS: The incidence of high grade PIN was 8%.
      High grade PIN does not cause sufficient changes in the clinical variables
      analyzed to suspect this lesion before it is confirmed by the pathological
      findings.

PMID- 11455766
TI  - [Preliminary experience with the Miami type ileocolonic urinary reservoir in the
      practice of oncologic gynecology].
AB  - OBJECTIVES: For many years we have used both ileal or colon conduits for urinary
      diversion during pelvic exenteration. Continent urinary reservoirs have replaced
      ileal and colon conduits as a method of urinary diversion at our institution. The
      aim of this study was to review the results and complications associated with
      continent urinary diversion in patients with gynecologic malignancies. METHODS:
      We reviewed the records of 26 patients who underwent construction of a continent
      urinary reservoir (Miami pouch) from February 1991 to June 1994 at the Department
      of Gynecologic Oncology of the National Cancer Institute of Mexico (Instituto
      Nacional de Cancerologia). Twenty-four of these patients had received
      radiotherapy for gynecologic malignancies. RESULTS: An ileocolonic continent
      urinary reservoir (Miami pouch) was created in 26 patients, aged 38-81 years, as
      part of a concurrent anterior or total pelvic exenteration for primary or
      recurrent gynecologic malignancies (19 pts.), for the relief of a vesicovaginal
      fistula (3 pts.), hemorrhagic cystitis (2 pts.), or in substitution of an ileal
      conduit (2 pts.), with follow-up ranging from 2-54 months. Additional procedures
      performed concurrently with the Miami pouch and pelvic exenteration included low
      rectal anastomosis (11 pts.), pelvic floor reconstruction (8 pts.), and vaginal
      reconstruction (4 pts.). The complications associated with the reservoir included
      incontinence (1 pt.), ureteral strictures (3 pts.), pouch leakage (1 pt.),
      difficult self-catheterization (4 pts.), and urosepsis and pyelonephritis (6
      pts.). One patient developed pouch stones. In this series, 95.6% of the patients
      were completely continent. No obstruction or reflux was noted in 92.3% of the
      cases. Nonsurgical management strategies used for reservoir-related complications
      included percutaneous nephrostomy, intravenous antibiotics, and percutaneous
      pouch decompression. Reoperation was required in 5 patients: one patient (early)
      due to a fistula, another patient required reimplantation due to obstruction, one
      patient with a nonfunctioning kidney underwent nephrectomy, and two patients with
      stoma stenosis. CONCLUSIONS: The Miami pouch is a low-pressure continent form of
      urinary diversion. The continence mechanism is easy to construct and the
      procedure can successfully be accomplished at the time of pelvic exenteration in
      patients with gynecologic malignancies. The rate of major complications of the
      Miami pouch is small and the continent urinary diversion can be undertaken with
      concurrent low rectal anastomosis or vaginal reconstruction.

PMID- 11455767
TI  - [Experience with cadaver renal transplant with ex situ reconstructed arteries].
AB  - OBJECTIVE: To review our experience with cadaveric kidney transplantation with ex
      situ reconstruction of damaged renal artery. METHODS: To obtain a minimum follow
      up of 5 years, 20 cases treated from January 1989 to December 1994 were
      retrospectively reviewed. The control group comprised 73 patients that had
      received an "ideal" graft during the same period. Both groups were similar for
      all the variables that could influence graft outcome. RESULTS: Both groups showed
      similar results for incidence of NTA, rejection episodes, creatinine values,
      surgical complications or reoperations. However, a strong trend (25% of the
      cases) to develop renal artery stenosis was found (p = 0.052). These latter cases
      were diagnosed by the onset of arterial hypertension that was difficult to
      control and were treated conservatively by percutaneous angioplasty with good
      functional results in 100% of the cases, although 80% required more than one
      session. This complication, however, did not lead to graft failure. CONCLUSIONS:
      Renal grafts with arteries damaged during procurement or as a result of
      pathological changes, such as arteriorclerosis or aneurysm, are useful after
      bench reconstruction before transplantation. However, the greater trend to
      develop symptomatic arterial stenosis that has been observed makes it convenient
      to look for this complication routinely during follow-up. If diagnosed and
      treated early, it does not influence the graft outcome. The therapeutic approach
      is first by percutaneous transluminal angioplasty and if it fails, then by open
      surgery.

PMID- 11455768
TI  - [Laparoscopy as essential method in the diagnosis of nonpalpable testis].
AB  - OBJECTIVE: To analyze the utility of laparoscopic evaluation in the diagnosis of
      the nonpalpable testis versus conventional imaging techniques based on our
      experience with 51 cases and data reported in the literature. METHODS/RESULTS:
      Testicular tumors were found in both intra-abdominal testes in one patient, as
      well as 7 cases of evanescent testis and 39 testicular rests in the inguinal
      canal. Four other intra-abdominal testes showed no changes. CONCLUSIONS: The
      possibility of an existing intra-abdominal testis and its possible progression to
      malignancy warrant exploration of the nonpalpable testis by laparoscopy, a very
      simple and effective procedure.

PMID- 11455769
TI  - [Hand-assisted laparoscopy].
AB  - OBJECTIVES: Laparoscopic surgery has not been extended enough among the
      urologists due to the inaccessibility of the retroperitoneal organs and
      consequently to the steep learning curve that is required. In this article we
      describe our experience in laparoscopic surgery assisted by the surgeon's hand
      introduced in the operating field. This is a technique that we have been using
      since 1994 and that has not been generally accepted until very recently. METHODS:
      Difficult nephrectomies and nephroureterectomies are considered to be the main
      indications for this technique. The approach to each kidney is described.
      RESULTS: The operating time is dramatically reduced. The surgeon's hand
      introduced intra-abdominally allows for a better control in difficult situations.
      The economic cost is lower. The use of analgesics and the recovery time in the
      postoperative period is similar to that of conventional laparoscopy. CONCLUSIONS:
      The optimal indication for this procedure are cases that require a very large and
      mutilating incision. The learning curve is significantly easier and it is an
      invaluable technique in cases considered until now to be unsuitable for an
      endoscopic procedure.

PMID- 11455770
TI  - [Response to intracavernous administration of 3 different drugs in the same group
      of patients with erectile dysfunction].
AB  - OBJECTIVE: To compare the subjective and objective penile rigidity in the same
      group of patients with erectile dysfunction after intracavernous injection of
      different vasoactive drugs. METHODS: 91 impotent males were randomly assigned to
      three groups of intracavernous injection: A: 20 micrograms PGE1 B: 30 mg
      papaverine hydrochloride + 1 mg phentolamine (bimix), and C: 10 micrograms PGE1 +
      15 mg papaverine hydrochloride + 0.5 mg phentolamine (trimix). Each patient was
      scheduled to receive the three modalities of intracavernous injection randomly
      with an interval of 7-10 days between injections. Penile rigidity equal to or
      more than 60% was considered positive. Subjective and objective penile rigidity
      were evaluated with callipers by the same observer. RESULTS: 82 patients
      completed the study and 9 dropped out after prolonged erection with one of the
      ICI modalities. Rigidity after treatment with C (66 +/- 15%) was significantly
      superior to that of B (59 +/- 15%, p = 0.0001) and A (60 +/- 13%, p = 0.0115). No
      differences were observed between A and B (p = 0.4644). Analysis of only the
      positive response showed significant differences between A and C, but not between
      C and B (p = 0.3323). Differences were not found between the response to PGE1 (A)
      and bimix (B) (p = 0.1275). The order of application of the drug had no effect on
      response (p = 0.026). CONCLUSIONS: A higher percentage of positive response in
      patients with erectile dysfunction was achieved with the trimix modality. Choice
      of more potent ICI regimens can improve the diagnostic and/or therapeutic
      efficacy in males that do not respond to PGE1 alone.

PMID- 11455771
TI  - [Antioxidative state and lipid peroxidation in erectile dysfunction: preliminary
      study].
AB  - OBJECTIVE: The aims of this study were to analyze the cavernosal tissue metabolic
      status of patients with vascular and psychogenic impotence and attempt to
      establish metabolic differences between these types of erectile dysfunction.
      METHODS: 103 patients were classified according to the type of erectile
      dysfunction into group A (vascular) and group B (psychogenic). Diagnosis was
      based on clinical history, physical examination, intracavernosal injection test,
      penile echo-doppler assessment, cavernosography-cavernosometry and nocturnal
      penile test. Cavernosal and peripheral venous blood samples were obtained from
      each patient and the lipoperoxide (LPO) levels and total antioxidant status (TAS)
      were determined. SPSS V9.0 was used for the statistical analysis. RESULTS: The
      mean age was 62 years (range 32-73). Cavernosal blood lipoperoxide levels were
      statistically higher (p < 0.05) in patients with vascular impotence (2.45
      mumol/L) than in those with psychogenic impotence (1.47 mumol/L). Cavernosal
      blood total antioxidant status was statistically higher (p < 0.05) in patients
      with psychogenic (1.40 mmol/L) than those with vascular impotence (1.10 mmol/L).
      The lipoperoxide levels and total antioxidant status for peripheral blood were
      1.68 mumol/L vs 1.60 mumol/L and 1.29 mmol/L vs 1.35 mmol/L, respectively, with
      no statistically significant differences between both groups. CONCLUSIONS:
      Cavernosal blood lipoperoxide levels and total antioxidant status can be an
      indicator of cavernosal tissue metabolic status and function.

PMID- 11455772
TI  - [Cutaneous horn of the penis].
AB  - OBJECTIVE: To describe a case of cutaneous horn of the penis and review its
      clinical and histological features. METHODS: The clinical and histological
      features of cutaneous horn of the penis are described. RESULTS/CONCLUSIONS:
      Cutaneous horn of the penis is an uncommon lesion that is diagnosed without
      difficulty. Treatment is by surgery with sufficient margins due to its possible
      association with malignant lesions.

PMID- 11455773
TI  - [Bilateral testicular microlithiasis].
AB  - OBJECTIVE: To report an uncommon case of testicular microlithiasis that was
      incidentally discovered. METHODS/RESULTS: A case of bilateral testicular
      microlithiasis in an 8-year-old boy that presented with a left scrotal cystic
      mass is described. Testicular microlithiasis was discovered on ultrasound
      evaluation. CONCLUSIONS: Bilateral testicular microlithiasis is a rare condition
      that requires control follow-up of tumor markers and by ultrasound since this
      condition has been associated with tumors.

PMID- 11455774
TI  - [Wilms tumor in the adult].
AB  - OBJECTIVE: To report a case of Wilms' tumor in an adult patient. METHODS: The
      records of an adult patient with renal tumor is reviewed. RESULTS: A 23-year-old
      male consulted for hematuria. Physical examination and patient assessment by
      ultrasound and CT showed a solid tumor in the right kidney. The patient was
      submitted to radical surgery. Pathological analysis demonstrated a biphasic
      nephroblastoma (Wilms' tumor) with infiltration of renal hilar fat (stage II).
      After surgery, adjuvant chemotherapy with vincristine-actinomycin D was
      administered for 60 weeks. CONCLUSIONS: Although rare in adults, Wilms' tumor
      should be included in the differential diagnosis of all renal tumors. Treatment
      is usually by surgery and chemotherapy with or without radiotherapy, depending on
      tumor stage.

PMID- 11455775
TI  - [Unusual localization of granulosa cell tumor].
AB  - OBJECTIVE: To present a case of granular cell tumor with an uncommon
      localization. METHODS: A 38-year-old patient presented with a painless nodule 10
      mm in diameter on the scrotum that he had noted two years earlier. RESULTS: The
      tumor was surgically excised. Pathological analysis demonstrated a granular cell
      tumor that was strongly positive for protein S-100 and negative for cytokeratin
      AE1-AE3 and CEA. CONCLUSIONS: Granular cell tumors are very frequent in the head
      and neck, but rare in the genitourinary region and are asymptomatic. Histological
      diagnosis is simple but should be confirmed by protein S-100 staining, which is
      positive in all cases. Treatment is by simple excision of the lesion. Tumor
      recurrence and metastasis have been reported, therefore follow-up is necessary.

PMID- 11455776
TI  - [Pelvic lipomatosis: contribution of a new case to the literature].
AB  - OBJECTIVE: To describe an additional case of pelvic lipomatosis, a rare condition
      that can be encountered by the urologist. METHODS/RESULTS: A 66-year-old patient
      consulted for irritative voiding syndrome and fever. Patient evaluation by IVP
      and CT demonstrated pelvic lipomatosis. CONCLUSIONS: Pelvic lipomatosis is a
      disease with variable clinical and radiological features. Careful follow-up is
      warranted for prevention and treatment of possible complications.

PMID- 11455777
TI  - [Reabsorption syndrome. Report of a case].
AB  - OBJECTIVE: To report a case of TURP syndrome and emphasize the importance of
      early diagnosis. METHODS: A case of reabsorption syndrome in a patient that
      underwent transurethral resection under spinal anesthesia is presented. RESULTS:
      Reabsorption syndrome (TURP syndrome) is manifested by neurological and
      hemodynamic changes resulting from absorption of irrigating fluid used during
      transurethral resection of the prostate. This complication presented in a patient
      undergoing elective surgery and with no additional risk factors. CONCLUSIONS:
      Since it is impossible to prevent this complication of TUR, spinal anesthesia
      should be utilized whenever possible because it permits early detection before
      important complications develop.

PMID- 11455778
TI  - [Syringocele of the Cowper's gland].
AB  - OBJECTIVE: To report an additional case of syringocele of Cowper's glands and
      briefly review its etiopathogenesis, diagnosis and treatment. METHODS/RESULTS: A
      26-year-old male consulted for a recent voiding syndrome and chronic postvoid
      dribbling. A voiding cystourethrogram demonstrated a syringocele, which was
      confirmed during endoscopic treatment. CONCLUSIONS: Syringocele or cystic
      dilatation of Cowper's gland duct usually has a congenital etiology. There are
      four morphological types: simple, perforated, imperforate and ruptured. Diagnosis
      is made by voiding cystourethrography and confirmed by endoscopy. Transperineal
      ultrasound was also utilized for the diagnosis. Treatment is by endoscopic
      incision.

PMID- 11455779
TI  - Maillard reactions of food proteins: chemical, nutritional and functional
      aspects.

PMID- 11455780
TI  - Kinetic aspects of the Maillard reaction: a critical review.
AB  - The literature concerning the kinetics of the Maillard reaction was critically
      discussed according to the initial, intermediate and advanced stages, as this is
      the way the Maillard reaction is traditionally analysed. For each stage, a
      division is made between simple kinetics and complex kinetics. Simple kinetics
      means that the general rate law is used and results are reported as zero-, first-
      or second-order reactions (sometimes a fractional order). It is emphasized that
      this approach for a complex reaction as the Maillard reaction only results in a
      mathematical fit procedure, not in mechanistic insight. The rate constants and
      activation energies derived are in fact composed of several elementary rate
      constants. With complex kinetics, i.e. trying to establish the kinetics for
      individual reaction steps, more mechanistic information can be extracted.
      However, there are conflicting results in literature and the interpretation is
      not always correct, as is shown in several examples. A summary of activation
      energies reported for the various stages in the Maillard reaction reveals large
      discrepancies, probably reflecting strong effects of experimental conditions on
      results that are obtained. Careful control of experimental conditions and proper
      kinetic analysis of the various stages in the Maillard reaction should lead to
      more consistent results in the future.

PMID- 11455781
TI  - News on the Maillard reaction of oligomeric carbohydrates: a survey.
AB  - The reaction behaviour of monosaccharides in the Maillard reaction is well
      investigated. Amadori compounds, for instance, form deoxyhexosuloses which are
      responsible for the formation of volatile flavour substances and melanoidins.
      These intermediates can be quantified by a trapping reaction with o
      phenylendiamine as stable quinoxalines. However the reaction behaviour of oligo
      and polymeric carbohydrates in non-enzymatic browning reactions are hardly known.
      Therefore maltooligosaccharides and in some cases starch were used together with
      glycine as model substances to investigate the Maillard reaction mechanism of
      oligo and polysaccharides. In quasi waterfree reaction systems oligosaccharides
      form alpha-dicarbonyl compounds via a "peeling off" mechanism. The Maillard
      reaction with the amino compound starts at the reducing end of an alpha-glucane
      residue and results in the formation of 1,4-dideoxyhexosulose. This is the main
      alpha-dicarbonyl compound found by trapping reaction with o-phenylendiamine
      during thermally induced degradation of maltooligosaccharides. The thermal
      reaction of maltooligosaccharides is accompanied by transglycosylations leading
      to formation of branched carbohydrate structures and by dehydrations forming
      anhydrosugars. The reaction mechanism which is responsible for degradation of
      oligomeric carbohydrates in aqueous model systems differs significantly from
      pathways mentioned above for water free reaction conditions. As the main alpha
      dicarbonyl compound 3-deoxypentosulose is formed which can be proved also by
      trapping reactions. Under aqueous reaction conditions the formation of other
      alpha-dicarbonyls plays only a marginal role in the Maillard reaction of
      oligomeric carbohydrates. In an aqueous system transglycosylation and dehydration
      of maltooligosaccharides are not important.

PMID- 11455782
TI  - Analysis of glycated proteins by mass spectrometric techniques: qualitative and
      quantitative aspects.
AB  - The analysis of protein glycation poses a difficult challenge due to the complex
      nature of the reaction. Of the several methods developed for the qualitative and
      quantitative evaluation of the glycation reaction between proteins and reducing
      sugars, soft ionization mass spectrometry is the most direct and reliable. In
      this paper we review the major mass spectrometric methods (ESI and MALDI mass
      spectrometry) used in the study of protein glycation. We also tested the
      assumption that limited glycation has little or no effect on the ionization
      potential of proteins and that the distribution profile of molecular ion peaks of
      different glycoforms in a mass spectrum reflect their solution composition in a
      mixture. The results confirm the validity of the above assumption under dilute
      solution conditions (0.2-0.6 g/ml total protein). A comparison of ESI and MALDI
      mass spectrometry in the analysis of protein glycation showed that both methods
      provide qualitative and quantitative analytical results, but the choice of
      instrument depends on the nature of the sample to be analysed, the level of
      accuracy and the type of information that is required.

PMID- 11455783
TI  - Advanced glycation endproducts (AGEs) as uremic toxins.
AB  - Products of non-enzymatic glycation accumulate both in diabetic and non-diabetic
      patients with renal failure. The increase in concentration is presumably due to
      increased generation, secondary to oxidative stress and due to decreased (renal)
      elimination; whether accumulation of AGEs of dietary origin plays a role is
      currently under investigation. AGE's have been related to progression of diabetic
      (and possibly also non-diabetic) renal disease and to a number of complications
      of the uremic syndrome. These comprise beta-2-microglobulin-derived dialysis
      related amyloidosis, dyslipidemia, vascular dysfunction and accelerated
      atherogenesis. A specific case is AGE related damage to the peritoneal membrane
      in CAPD patients. Removal of AGE by dialysis is negligible and even high flux
      dialysis eliminates only a quantitatively limited amount of AGE. In contrast, a
      rapid decrease of AGE concentrations in plasma is noted after renal
      transplantation. Dietary AGEs may contribute significantly to the total AGE load
      of the body, particularly in uremia.

PMID- 11455784
TI  - Metabolic transit of Amadori products.
AB  - In several studies, the absorption and urinary excretion of free and protein
      bound Amadori products were measured in rats and humans. Both, in vitro tests
      with everted intestinal sac preparations and in vivo experiments, showed that
      there is no active intestinal transport of these compounds but an absorption by
      diffusion. Trials with tissue slices have shown that there was an uptake into the
      cells of the liver, kidneys and muscles. Metabolism of Amadori products, if it
      exists in animals, tends to be very low. Micoorganisms in the large intestines
      decompose the Amadori products almost completely. The profile of urinary
      excretion of Amadori products after the ingestion of test meals showed a rapid
      elimination of the absorbed part, while the fecal output, although low because of
      the hind gut fermentation, persisted up to 3 days. Only 1-3% of the ingested
      amounts of protein bound Amadori products were recovered in the urine, which
      suggests a low absorption rate.

PMID- 11455785
TI  - Radio fluorination and positron emission tomography (PET) as a new approach to
      study the in vivo distribution and elimination of the advanced glycation
      endproducts N epsilon-carboxymethyllysine (CML) and N epsilon-carboxyethyllysine
      (CEL).
AB  - After synthesis of fluorine-18 labelled analogues by [18F]fluorobenzoylation at
      the alpha-amino group, biodistribution and elimination of individual advanced
      glycation endproducts, namely N epsilon-carboxymethyllysine and N epsilon
      carboxyethyllysine, were studied in comparison to lysine in rats after
      intravenous injection using positron emission tomography (PET). The
      [18F]radiofluorinated amino acids were fast distributed via the blood, followed
      by a rapid excretion through the kidneys. Elimination kinetics were similar for
      both AGEs and lysine. For CML and CEL, but not for lysine, a temporary liver
      accumulation could be observed, which was not connected with any metabolisation
      or enterohepatic circulation. No further accumulation in any tissues was
      observable, indicating that increased tissue levels of CML or CEL, which have
      been described for certain disorders, are exclusively derived from endogenous
      origin and should not depend on a dietary intake. However, under uremic
      conditions, an impaired kidney function might result in a significant increase of
      the AGE-load of blood and tissues. PET based on 18F-labelled AGEs proved to be a
      promising tool to elucidate the physiological fate of post-translationally
      modified amino acids and to clarify the role of AGEs as possible "glycotoxins".

PMID- 11455786
TI  - Determination of the molecular weight distribution of non-enzymatic browning
      products formed by roasting of glucose and glycine and studies on their effects
      on NADPH-cytochrome c-reductase and glutathione-S-transferase in Caco-2 cells.
AB  - After thermal treatment of a mixture of glucose and glycine for 2 h at 125
      degrees C, about 60% of the starting material was converted into non-soluble,
      black pigments, whereas 40% of the mixture was still water-soluble. Dialysis of
      the latter fraction revealed 30.4% of low molecular weight compounds (LMWs; MW <
      10,000 Da) and 10.0% high-molecular weight products (HMWs; MW > or = 10,000 Da).
      The water-soluble Maillard reaction products (MRPs) were separated by gel
      permeation chromatography and ultrafiltration, revealing that 60% of the water
      soluble products of the total carbohydrate/amino acid mixture had MWs < 1,000 Da
      and consisted mainly of non-coloured reaction products. MRPs with MWs between
      1,000 and 30,000 Da were found in comparatively low yields (about 1.3%). In
      contrast, about 31.1% of the MRPs exhibited MWs > 30,000 Da, amongst which 14.5%
      showed MWs > 100,000 Da, thus indicating an oligomerisation of LMWs to
      melanoidins under roasting conditions. To investigate the physiological effects
      of these MRPs, xenobiotic enzyme activities were analysed in intestinal Caco-2
      cells. For Phase-I NADPH-cytochrome c-reductase, the activity in the presence of
      the LMW and HMW fraction was decreased by 13% and 22%, respectively. Phase-II
      glutathione-S-transferase activity decreased by 15% and 18%, respectively, after
      incubation with the LMW and the HMW fractions. Considering the different yields,
      30% and 10%, respectively, of the LMW and the HMW fractions, the total amount of
      the LMW fraction present in the glucose-glycine mixture is more active in
      modulating these enzyme activities than that of the HMW fraction.

PMID- 11455787
TI  - Occurrence of galactosyl isomaltol and galactosyl beta-pyranone in commercial
      drinking milk.
AB  - Occurrence of galactosyl isomaltol (GAI) and galactosyl beta-pyranone (GAP), two
      advanced glycosylation end products arising from the Maillard reaction of lactose
      via 1-deoxyosone pathway, was studied in commercial drinking milk. Galactosyl
      isomaltol was extracted from milk spiked with this isomaltol glycoside avoiding
      usage of any deproteinizing agent and was determined by a sensitive and
      interference-free HPLC method. No quantifiable amount of GAI proved to be present
      in any type of drinking milk, suggesting that some data reported in literature
      arise from uncontrolled conversion of GAP into GAI. The standard molecule of GAP
      was produced by heating a model system containing lysine and [U-14C]lactose,
      purified by solid phase extraction (SPE) on a C18 cartridge eluting with water,
      separated by the inverse distance function (IDF) standard HPLC method specified
      for lactulose determination, and characterized by both spectroscopic data and
      tandem mass spectrometry. The behaviour of formation of GAP and GAI in model
      systems containing lysine and lactose, heated under conditions of in bottle
      sterilization of milk, was studied in a wide range of values of the molar ratio
      lysine to lactose. While GAP easily forms as soon as lysine is present in the
      system, GAI does not form below a value of 0.1 of this molar ratio, so explaining
      why this compound is not present in commercial drinking milk. Amounts of GAP
      varying from 0.04 to 43.1 mumol/l were found in the different types of drinking
      milk ranging from high temperature pasteurized to in bottle sterilized, proving
      that this compound is a stable and sensible marker for evaluating the extent of
      the advanced Maillard reaction, hence the heating severity of commercial drinking
      milk. Moreover, GAP can be determined after conversion into GAI under acid warm
      conditions with a yield of 0.5 mol GAI from 1 mol GAP. Values of GAP obtained on
      commercial milk samples either by the direct HPLC method or after conversion into
      GAI were rather comparable, but the latter method needs further study in view of
      routine application.

PMID- 11455788
TI  - The FAST method, a rapid approach of the nutritional quality of heat-treated
      foods.
AB  - The FAST method is based on the determination of maximal fluorescence emission
      when exciting at 330-350 nm, which corresponds to molecular structures formed
      between reducing sugars or oxidizing lipids and lysine residues of proteins. This
      fluorescence is dependent on heat treatment and related to protein nutritional
      loss. Applied to a soluble extract of the food and corrected for the protein
      concentration of the solution obtained, using Trp fluorescence, the method allows
      to calculate the FAST index (FI), an indicator of the nutritional damage during
      heat process. The method, firstly validated on milk samples, is demonstrated here
      to well correlate with lysine damage on various food products, such as heat
      treated milk and breakfast cereals, essentially modified by the Maillard
      reaction, and roasted soybean or cooked salmon, where interactions between
      oxidizing lipids and proteins better take place. Independently on the food
      product or the type of heat process, the FAST index appears always well
      correlated (r2: 0.84-0.98) to the lysine loss, the latter being estimated by
      determination of acid-released lysine, fluorescamine-reactive lysine or infrared.
      Shortly, roasted corn flakes appeared to be more damaged than extrudated flour
      (FI 100 and lysine blockage 40% instead of 55 and 30%), condensed milk more than
      UHT milk (FI 150 and 85% of acid-released lysine instead of 80 and 94%), and
      steam-cooked salmon much less than pan-fried (FI 28 instead of 372). Roasted soy
      can reach FI of more than 300 corresponding to chemical lysine loss of 40% and
      poultry-digestive lysine loss of 100%. As a conclusion, the FAST method, once
      precisely calibrated with pertinent nutritional indicators, should be of great
      interest for controlling or adapting a process in order to ensure a better
      nutritional quality for the food product.

PMID- 11455789
TI  - Determination of the Maillard product oxalic acidmonolysinylamide (OMA) in heated
      milk products by ELISA.
AB  - Oxalic acid monolysinylamide (OMA), a Maillard product which had initially been
      identified as a reaction product of L-ascorbic acid, was formed, dependent on the
      reaction conditions, also from other carbohydrate sources. At elevated
      temperatures and in the presence of oxygen, the reaction of lactose with proteins
      resulted in the formation of relatively high amounts of OMA. Using a polyclonal
      antibody, which bound with high specificity and affinity to OMA-modified
      proteins, a competitive enzyme linked immunosorbent assay (ELISA) was developed
      to measure OMA formation in heat-treated milk products. The assay performance was
      characterized for OMA-modified beta-lactoglobulin diluted in buffer or
      pasteurized milk. For the latter, the least detectable dose was determined as 1.4
      ng/ml with a linear range for quantification between 2 ng/ml and 200 ng/ml. For
      some samples intra- and interassay variation were determined. The ELISA was used
      to measure OMA-formation in heated milk and commercially available infant
      formula.

PMID- 11455790
TI  - Identification and quantitative evaluation of the lysine-arginine crosslinks
      GODIC, MODIC, DODIC, and glucosepan in foods.
AB  - The presence of the various protein crosslinks GOLD 2, MOLD 3, GODIC 4, MODIC 5,
      DODIC 6, and glucosepan 7 in foods has been established for the first time by
      liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization
      (ESI). In compounds 2 and 3 two lysine moieties, in 4-7 a lysine and an arginine
      side chain are joined by the crosslink. Unequivocal identification of 2-7 was
      achieved with independently synthesized reference material. The quantitative
      results for the investigated foodstuffs show MODIC 5 to be the most important
      Maillard crosslink. The concentrations of 5 and GODIC 4 are 5-10 fold higher than
      those of the corresponding imidazolium compounds 3 and 2, establishing 5 and 4 as
      the major food protein crosslinks derived from methylglyoxal and glyoxal,
      respectively. The maximum value of 151 mg MODIC 5/kg protein (equivalent to 0.42
      mmol/kg protein) was found in a butter biscuit sample which also shows the
      highest overall Maillard crosslink content with 0.71 mmol 47/kg protein. These
      first quantitative results suggest that compounds 4-7 can be jointly responsible
      for protein polymerization in the course of food processing.

PMID- 11455791
TI  - On the influence of non-enzymatic crosslinking of caseins on the gel strength of
      yoghurt.
AB  - After storage of UHT milk at 37 degrees C resp. 50 degrees C, yoghurt was
      prepared. For a storage temperature of 37 degrees C, breaking strength of the
      yoghurt samples increased from 2.7 to 5.8 N with increasing storage duration of
      the UHT milk. A plateau is reached after 17 days of storage. This increase in
      breaking strength correlates with a significant increase in non-reducible casein
      oligomerization from 14% for fresh UHT milk to 25% measured using size exclusion
      chromatography under reducing and denaturing conditions and calculated as sum of
      predominantly formed dimers and trimers at the total casein fraction. At a
      storage temperature of 50 degrees C, a less increase in breaking strength from
      2.7 to 4.6 N with a plateau after 17 days was observed while casein
      oligomerization increased to 63%. After acid hydrolysis, only lysinoalanine and
      histidinoalanine were detected in the caseinate samples via amino acid analysis.
      The quantified concentration of lysinoalanine and histidinoalanine could not
      explain the observed casein oligomerization. Thus, unknown crosslinked amino
      acids must have been formed during storage, inducing significant changes in the
      functional properties of milk proteins.

PMID- 11455792
TI  - Selective fortification of lysinoalanine, fructoselysine and N epsilon
      carboxymethyllysine in casein model systems.
AB  - In the present study, a promising strategy to study nutritional effects of
      selected chemical reaction products formed in heat treated protein containing
      foods is addressed. In due course, a selective fortification of different marker
      compounds for lysine damage in casein-sugar mixtures was performed to provide
      model systems being applicable to investigate biological effects of the cross
      link lysinoalanine (LAL), the MRPs fructoselysine (FL) and N epsilon
      carboxymethyllysine (CML) in a casein-linked preparation. The three different
      model proteins, casein-LAL, casein-FL and casein-CML were prepared by heating
      casein either in strong alkaline conditions at 105 degrees C for 1 h, in the
      presence of glucose at 65 degrees C for 68 h, or in the presence of glyoxylic
      acid at 37 degrees C for 19 h. Finally, the degree of lysine modification
      achieved was 39%, 75% and 55% for the casein-LAL, casein-FL and casein-CML,
      respectively. The calculation of lysine recovery and the respective analysis of
      each single modified casein (LAL-, FL- and CML-MP) for the selected fortified
      compound and each other compound vice versa proved that the individual procedure
      provides a specific fortification for LAL, FL and CML, respectively. The modified
      proteins are suitable as reference model proteins to be investigated for specific
      biological and toxicological effects of casein-linked LAL, FL and CML.

PMID- 11455793
TI  - New antimalarial treatment for KwaZulu-Natal.

PMID- 11455794
TI  - Capitation versus fee-for-service.

PMID- 11455795
TI  - Can KwaZulu-Natal hospitals cope with the HIV AIDS human tide?

PMID- 11455796
TI  - A pill for every ill: some different prescriptions.

PMID- 11455797
TI  - Access to essential medications for HIV/AIDS in South Africa.

PMID- 11455798
TI  - An audit of private sector neonatal admissions.

PMID- 11455799
TI  - An atypical carbohydrate-deficient glycoprotein (CDG) syndrome patient in South
      Africa.

PMID- 11455801
TI  - Palliative care.

PMID- 11455802
TI  - An outbreak of food poisoning among children attending an international sports
      event in Johannesburg--don't let it happen again!

PMID- 11455803
TI  - Ultrasound in obstetrics and gynaecology--quo vadis?

PMID- 11455804
TI  - Thrombo-embolic disease--prevalence of factor V Leiden in the Western Cape.

PMID- 11455805
TI  - A case of infective endocarditis caused by a viridans group streptococcus
      resistant to ceftriaxone.

PMID- 11455806
TI  - The South African National Non-Natural Mortality Surveillance System--rationale,
      pilot results and evaluation.
AB  - BACKGROUND: While individual mortuaries have recorded data for non-natural deaths
      in time-limited studies, there have been no systematic efforts to draw forensic
      medical services and state mortuaries into a nationwide fatal injury surveillance
      system. Beginning in June 1998, the National Non-Natural Mortality Surveillance
      System (NMSS) commenced pilot operation. OBJECTIVE: To evaluate the NMSS and
      illustrate its utility from sample findings. DESIGN: Data entered into the system
      by mortuary staff were checked against a random sample of cases for which
      separate forms were completed by an independent researcher. Process observations
      and follow-up with data users were used to assess the system's acceptability,
      timeliness and data usefulness. SETTING: Eighteen mortuaries in six provinces
      representing approximately 35,000 cases per year, or around 50% of all non
      natural deaths. PARTICIPANTS: The National Departments of Health; Safety and
      Security; and Arts, Culture, Science and Technology; national and provincial
      forensic medico-legal services; the South African Police Services; universities
      and science research councils. MAIN OUTCOME MEASURES: Surveillance system
      simplicity, flexibility, acceptability, sensitivity, positive predictive value,
      representativeness, timeliness, data usefulness and resources. RESULTS: The NMSS
      was established at 10 target sites. Lack of equipment, personnel resistance, and
      closure of some mortuaries prevented implementation in the remaining eight
      mortuaries. Sensitivity was internally assessed and ranged from 65% to 95% for
      manner of death. Positive predictive value was also internally measured, and
      ranged from 74% to 80% for manner of death and from 71% to 82% for mechanism of
      death. Timeliness was good, and basic reports covering most items were available
      6 weeks after a case had been examined. While staff found the system simple,
      acceptability depended on the individuals involved at different mortuaries, and
      the system was compromised to some extent by bureaucratic barriers. End users
      found the data to be of great value. NMSS set-up costs totalled approximately
      R26,000 per mortuary, and it is estimated that maintenance costs will be R8.00
      per case registered. CONCLUSIONS: With minimal resources, the NMSS uses existing
      investigative procedures to describe and report the epidemiology of fatal
      injuries. The pilot study demonstrates the feasibility of the system, and
      identifies the need to remove organisational constraints and individual barriers
      if it is to be sustained and expanded beyond the pilot sites.

PMID- 11455807
TI  - An outbreak of food poisoning among children attending an international sports
      event in Johannesburg.
AB  - OBJECTIVES: To describe an outbreak of food poisoning at a major international
      sports event in Johannesburg and to determine the likely cause and source of the
      outbreak. DESIGN: A descriptive, case-control study. SETTING: An international
      sports event in Johannesburg. METHODS: A questionnaire survey of involved
      children was used to conduct a case-control study. Microbiological and chemical
      analysis of the implicated food was undertaken. Site visits to the premises
      involved in food preparation were conducted. RESULTS: A total of 578 children
      were involved. Of the 361 children who returned questionnaires, 134 were affected
      by an acute-onset emetic-type illness, while 53 children developed diarrhoea.
      Consumption of fruit juice was associated with acute illness, while diarrhoea was
      associated with the consumption of maize-meal porridge (pap) and chicken stew.
      Microbiological analysis revealed high bacterial loads in samples of the fruit
      juice and the presence of Shigella flexneri in the maize-meal porridge. Visits to
      the suppliers of the implicated foods revealed several deficiencies in terms of
      food hygiene precautions. CONCLUSION: The likely vehicles and causes of this
      outbreak are elucidated. Guidelines for monitoring the supply and distribution of
      food to future similar events should be established. Furthermore, hospitals
      should have protocols in place to deal with such outbreaks in a manner that
      facilitates epidemiological investigation.

PMID- 11455808
TI  - Prevalence of emotional, physical and sexual abuse of women in three South
      African provinces.
AB  - INTRODUCTION: There is growing recognition in the ranks of the South African
      government that violence against women is a serious problem facing us all. Until
      now data on the epidemiology of violence against women in South Africa have been
      scanty. This report presents the findings of the first major community-based
      prevalence study. OBJECTIVES: To describe the prevalence of physical, sexual,
      financial, and emotional abuse of women. METHODS: A cross-sectional study
      conducted in the Eastern Cape (EC), Mpumalanga (MP) and the Northern Province
      (NP). The sample included one randomly selected woman aged 18-49 years living in
      each of 2,232 households. The sample was drawn using stratified, multistage,
      random methods, and 1,306 questionnaires were completed, giving a 90.3% response
      rate after adjusting for households without an eligible woman. RESULTS: The
      prevalences of ever having been physically abused by a current or ex-partner were
      26.8% (EC), 28.4% (MP) and 19.1% (NP). The prevalences of abuse in the last year
      were 10.9% (EC), 11.9% (MP) and 4.5% (NP). The prevalences of rape were 4.5%
      (EC), 7.2% (MP) and 4.8% (NP). Considerable emotional and financial abuse was
      also reported, e.g. the prevalences of a partner having boasted about or brought
      home girlfriends in the previous year were 5.0% (EC), 10.4% (MP) and 7.0% (NP):
      The prevalences of physical abuse during a pregnancy were 9.1% (EC), 6.7% (MP)
      and 4.7% (NP). The proportions of abused women who were injured in the year
      before the survey were 34.5% (EC), 48.0% (MP) and 60.0% (NP). CONCLUSIONS: This
      study is the first large-scale, community-based prevalence study to be undertaken
      in South Africa.

PMID- 11455809
TI  - Non-fatal suicidal behaviour in women--the role of spousal substance abuse and
      marital violence.
AB  - OBJECTIVE: To investigate the precipitants of non-fatal suicidal behaviour in
      women using a gender-based comparison. DESIGN: A retrospective analysis of case
      records. Data were analysed using chi-square tests of significance. SUBJECTS: One
      hundred men and 100 women admitted for non-fatal suicidal behaviour at a general
      hospital. OUTCOME MEASURES: Subjects' biographical details and self reports of
      precipitating factors such as marital conflict, spousal extramarital affairs,
      alcohol abuse and marital violence. RESULTS: Significantly more married women
      than men cited spousal extramarital affairs, spousal alcohol abuse and marital
      violence as precipitants of their self-destructive behaviours. CONCLUSION: The
      findings emphasise the role of spousal behaviour and resultant stress in
      precipitating non-fatal suicidal behaviour in women. Preventive efforts must
      focus on the psychological, social and economic empowerment of women.

PMID- 11455810
TI  - Side-effects of oral misoprostol in the third stage of labour--a randomised
      placebo-controlled trial.
AB  - BACKGROUND: Misoprostol, an inexpensive, stable, orally active prostaglandin
      analogue, has been suggested for use in the prevention of postpartum haemorrhage.
      Potential side-effects, however, need to be quantified. OBJECTIVE: To compare the
      rate of postpartum shivering and pyrexia following oral misoprostol 600
      micrograms and placebo. DESIGN: A double-blind placebo-controlled trial. Women in
      labour were randomly allocated to receive either misoprostol 600 micrograms
      orally or placebo after delivery. Conventional oxytocics were given immediately
      if blood loss was thought to be more than usual. Side-effects were recorded.
      Postpartum blood loss in the first hour was measured by collection in a special
      flat plastic bedpan. SETTING: The labour ward of an academic hospital in
      Johannesburg, with 7,000 deliveries per annum. MAIN OUTCOME MEASURES: Shivering
      and pyrexia. RESULTS: The groups were well matched. Misoprostol use was
      associated with more shivering (44% versus 11%, relative risk (RR) 4.03, 95%
      confidence interval (CI) 2.85-5.70), pyrexia > or = 37.8 degrees C (38% v. 6%, RR
      6.23, CI 3.89-9.97), 1-hour systolic blood pressure > or = 140 mmHg (33% v. 25%,
      RR 1.32, CI 1.03-1.70), and diastolic blood pressure > or = 90 mmHg (10.5% v.
      3.0%, RR 3.44, CI 1.67-7.11). There were no other significant differences. The
      study was not designed to be large enough to assess a difference in blood loss >
      or = 1,000 ml (9% v. 9.7%, RR 0.93, CI 0.56-1.53). Possible effects on blood loss
      may have been obscured by the lesser use of additional oxytocics in the
      misoprostol group (14% v. 18%, RR 0.78, CI 0.54-1.13). CONCLUSIONS: This study
      has shown the association of postpartum oral misoprostol 600 micrograms with
      shivering, pyrexia and hypertension. The increased blood pressure, as for the
      trend towards increased abdominal pain, may be secondary to the uterotonic effect
      of misoprostol. Large randomised trials are needed to assess the effectiveness of
      misoprostol in the prevention of postpartum haemorrhage, against which the
      disadvantages demonstrated here can be weighed.

PMID- 11455811
TI  - A review of in situ measurement of organic compound transformation in
      groundwater.
AB  - Laboratory assessments of the rate of degradation of organic compounds in
      groundwater have been criticized for producing unrepresentative results. The
      potential for organic compounds to be transformed in groundwater has been
      measured using in situ methods, which avoid problems of attempting to duplicate
      aquifer conditions in the laboratory. In situ assessments of transformation rates
      have been accomplished using transport studies and in situ microcosms (ISMs); a
      review of these methods is given here. In transport studies, organic solutes are
      injected into an aquifer and the concentrations are monitored as they are
      transported downgradient. The change in mass of a solute is determined by the
      area contained under the breakthrough curve (plot of concentration versus time).
      ISMs isolate a portion of the aquifer from advective flow and act as in situ
      batch reactors. Experiments using ISMs involve removing water from the ISM,
      amending it with the solutes of interest, re-injecting the amended water, and
      monitoring the solute concentrations with time. In both transport and ISM
      studies, the loss of organic solutes from solution does not allow a distinction
      to be made between sorptive, abiotic and biotic transformation losses. Biological
      activity can be chemically suppressed in ISMs and the results from those
      experiments used to indicate sorption and abiotic loss. Transformation products
      may be monitored to provide additional information on transformation mechanisms
      and rates.

PMID- 11455812
TI  - An appraisal of methods for measurement of pesticide transformation in the
      groundwater zone.
AB  - Laboratory and field studies show that pesticides may be transformed in the
      groundwater zone. Possible reaction mechanisms are chemical hydrolysis, catalytic
      reduction and aerobic or anaerobic microbial transformation. Transformation in
      the groundwater zone can be an important element in the advanced evaluation of
      the potential risk arising from a pesticide in the public drinking water supply.
      However, rate and pathway of transformation can show large differences, depending
      on the bio-geochemical conditions in the groundwater zone. Knowledge of the
      reaction mechanisms and the effect of aquifer conditions would allow vulnerable
      and low-vulnerable application areas for a pesticide to be delimited. An outline
      is given of possible approaches to quantifying these transformation processes and
      using the results in registration procedures, especially in the EU and its member
      states. Furthermore, areas where there is need for continued research and better
      understanding are highlighted.

PMID- 11455813
TI  - Degradation of herbicides in shallow Danish aquifers: an integrated laboratory
      and field study.
AB  - Degradation of pesticides in aquifers has been evaluated based on a number of co
      ordinated field and laboratory studies carried out in Danish aquifers. These
      studies included investigations of vertical and horizontal variability in
      degradation rates from the vadose zone to an aquifer, the effects of aerobic
      versus anaerobic conditions, and the importance of concentration on degradation
      kinetics for a selected range of herbicides. The studies were based on different
      experimental approaches ranging from simple batch experiments to column studies
      to field injection experiments and, where appropriate, results were compared.
      Some herbicides were degraded under aerobic conditions (some phenoxy acids, DNOC
      and glyphosate) and others under aerobic conditions (other phenoxy acids, DNOC;
      there was some indication of atrazine transformation). Certain pesticides were
      not degraded in any investigations (dichlobenil, the dichlobenil metabolite 2,6
      dichlorobenzamide (BAM), bentazone, isoproturon, metamitron and metsulfuron
      methyl). The spatial variability was substantial, since hardly any of the
      investigated pesticides were degraded in all comparable samples. This means that
      it is very difficult to claim that a given pesticide is readily degradable in
      aquifers. However, the experimental approaches used (with incubations lasting
      more than a year) may not be sensitive enough to verify the low degradation rates
      that may be significant as a result of the long retention time of groundwaters.

PMID- 11455814
TI  - Quantification of acetochlor degradation in the unsaturated zone using two novel
      in situ field techniques: comparisons with laboratory-generated data and
      implications for groundwater risk assessments.
AB  - Degradation of the herbicide acetochlor in the unsaturated zone was quantified
      using two unique in situ field techniques. The DT50 values generated at two
      different sites on surface soil and two subsoil depths using these techniques
      were compared with values generated under aerobic laboratory-incubation
      conditions (typically 20 degrees C, 40% maximum water holding capacity).
      Additionally, laboratory-degradation data were generated on surface and subsoils
      from four other sites. All subsoils were treated with acetochlor at 5% of the
      surface soil application rate. Acetochlor degradation in both field- and
      laboratory-incubated subsoils was rapid and often exceeded surface soil rates.
      Field and laboratory DT50 values from all sites ranged from 2 to 88 days in
      subsoil, compared with a range of 1 to 18 days in surface soils. The DT50 results
      from in situ field techniques were comparable with those generated from
      laboratory incubations in the same soils, confirming the validity of performing
      laboratory-based degradation studies to determine pesticide DT50 values in
      subsoils. Microbiological characterisation of selected soils revealed that
      subsoils had a viable and active population, although direct counts of bacteria
      were consistently lower in subsoil (10(8)-10(9) g-1 dry soil) compared with
      surface soils (10(10) g-1 dry soil). The leaching models used to perform
      groundwater risk assessments (e.g. PELMO, PESTLA, MACRO-DB, PRZM and the FOCUS EU
      leaching scenarios) have provision for inclusion of subsoil degradation rates.
      However, conservative default estimates are typically used, as no other
      alternative is available. Results presented here show that these default values
      may significantly underestimate true subsoil degradation contributions, and
      therefore not accurately predict pesticide concentrations in groundwater. The
      degradation data generated for acetochlor were applied to the mathematical model
      PELMO to demonstrate the importance of the inclusion of subsoil degradation data
      in groundwater risk assessment models and thereby in the registration of
      pesticides in Europe.

PMID- 11455815
TI  - Degradation of imazosulfuron in soil.
AB  - Imazosulfuron, 1-(2-chloroimidazo[1,2-alpha]pyridin-3-ylsulfonyl)-3- (4,6
      dimethoxypyrimidin-2-yl)urea, is a new post-emergence sulfonylurea herbicide
      applied once per growing season, highly active at low application levels, used to
      control most annual and perennial broad-leaf weeds and sedges in paddy rice (75
      95 g AI ha-1) and turf (500-1000 g AI ha-1), and characterised by low mammalian
      toxicity. The degradation of imazosulfuron in a sandy loam soil (10-15 cm depth)
      has been investigated under aerobic and anaerobic laboratory conditions to
      evaluate its likely environmental fate. Test soils were treated with
      imazosulfuron in acetonitrile to give a final concentration of 0.2 mg kg-1 (100 g
      ha-1). The treated soils were extracted with methylene chloride + acetonitrile +
      1 M ammonium hydroxide (4 + 15 + 1 by volume) and analysed by HPLC. Recoveries
      from spiked soils ranged from 80% to 95% (RSD 0.5-2.5%; n = 3) for imazosulfuron
      and its metabolites 2-chloroimidazo[1,2-alpha]pyridin-3-sulfonamide (IPSN), 1-(2
      chloroimidazo[1,2-alpha]pyridin-3-ylsulfonyl)-3-(4-hydroxy-6- methoxypyrimidin-2
      yl)urea (HMS) and 2-amino-4,6-dimethoxypyrimidine (ADPM). The limits of
      quantitation ranged from 0.001 mg kg-1 to 0.005 mg kg-1. Chemical cleavage of the
      sulfonylurea bond to give ADPM and IPSN was the main degradation pathway in
      aerobic conditions, whereas a remarkable production of HMS under anaerobic
      conditions suggested that degradation was due to micro-organisms which had the
      ability to demethylate imazosulfuron. In aerobic and anaerobic conditions,
      imazosulfuron disappeared from the soil with a half-life of approximately 70 (90%
      CL 62-75; r2 = 0.98) and 4 (90% CL 3.2-4.2; r2 = 0.97) days, respectively.

PMID- 11455816
TI  - Kinetics of chemical degradation of isoxaflutole: influence of the nature of
      aqueous buffers (alkanoic acid/sodium salt vs phosphate).
AB  - A kinetic study of the chemical degradation of isoxaflutole (5-cyclopropyl-1,2
      oxazol-4-yl alpha alpha alpha-trifluoro-2-mesyl-p-tolyl ketone) into its
      diketonitrile derivative (DKN), which is its active herbicide principle, in
      organic buffers at different pH values was carried out using a HPLC/UV detection
      method. The values of the pseudo-first-order rate constants Kobs for the reaction
      were calculated and compared with those previously obtained in inorganic buffers.
      In both cases, Kobs was found to be dependent on pH and temperature, but at pH
      5.2 the degradation of isoxaflutole in CH3COOH/CH3COONa buffers was considerably
      faster than in KH2PO4/Na2HPO4 buffers, indicating that the compound was sensitive
      to the nature of the reagents used to prepare buffered solutions. The influence
      of phosphate and acetate concentrations and the influence of the R-substituent in
      RCOOH/RCOONa buffers were investigated. For the HA/A- buffers studied, the values
      of Kobs were linearly dependent on HA and A- concentrations, which meant that the
      degradation of isoxaflutole was subject to general catalysis. The values of Kobs
      were also found to be dependent on the number and the position of the CH3 groups
      of the R-substituent. The known degradation product of DKN (a benzoic acid
      derivative) was not detected throughout this study.

PMID- 11455817
TI  - Photochemical transformation of acifluorfen under laboratory and natural
      conditions.
AB  - Acifluorfen was irradiated in pure water at various excitation wavelengths and pH
      values. Numerous photoproducts were obtained which were identified by [1H]NMR
      and/or HPLC-MS/MS. The main reaction pathways were photo-decarboxylation, photo
      cleavage of the ether bonding with formation of phenolic compounds, photo
      dechlorination and photo-Claisen type rearrangement. Decarboxylation was observed
      in acidic and neutral media whereas cleavage of the ether bonding dominated in
      basic media. The photo-Claisen type rearrangement only occurred on excitation at
      short wavelengths. The quantum yield of photolysis was significantly lower at 313
      nm (6.1 x 10(-5)) than at 254 nm (2.0 x 10(-3)). The photoreactivity of
      acifluorfen was then studied in conditions approaching environmental conditions.
      Acifluorfen was dissolved in pure water, in water containing humic substances or
      in a natural water, and exposed to solar light in June at Clermont-Ferrand
      (latitude 46 degrees N). In pure water, the half-life was estimated at 10 days
      and photo-decarboxylation accounted for 30% of the conversion. The presence of
      humic substances (10 mg litre-1) did not affect the rate of photo-transformation.
      However, the half-life of acifluorfen dissolved in the natural water was only 6.8
      days.

PMID- 11455818
TI  - Dynamics and mechanism of ultraviolet photolysis of atrazine on soil surface.
AB  - The photolysis of atrazine in the soil surface under UV light and the factors
      affecting this has been studied. A rate constant of 0.09-0.17 min-1, photolytic
      depth of 0.1-0.3 mm and half-life of 4-8 min were determined. The results show
      that soil granularity, pH, humidity, organic content, humic acid and surface
      active agents could affect the photolysis of atrazine in soil. GC-MS showed three
      photolytic products: 1-sec-butyl-4,4-diethyl-1-tetrazene, N2,N4-diethyl-6-methyl
      1,3,5-triazine-2,4-diamine and 6-chloro-N2-propyl-1,3,5-triazine-2,4-diamine. The
      mechanism of the photolytic process is discussed.

PMID- 11455819
TI  - Strangers in the house? Communication between mothers and their hearing impaired
      children who sign.
AB  - Many hearing impaired children rely on signing as a method of communication and
      are educated through this medium at school. While there is a paucity of
      information on the use of signing in the home, the impression in the literature
      is that these children are often unable to communicate through this medium in
      their homes. This has serious implications for family relationships as well as
      the personal well-being, educational success and social integration of the child.
      The present study explored the signing experience of 45 mothers of children in
      the junior primary phase at schools for the deaf in the Durban region of Kwa-Zulu
      Natal as a reflection of the use of signing within the home. A descriptive survey
      design, using two researcher administered questionnaires, was used to obtain
      information on the signing practice of mothers, exploring aspects related to the
      extent to which signing is used, the type of signing used and signing
      proficiency. The findings revealed mothers' signing skill to be inadequate in
      terms of their own assessment on rating scales and descriptions of their signing.
      They signed less frequently than their children did, using speech more often, and
      with the vast majority using simultaneous communication when they did sign.
      Signing ability was judged to be below that of their children, with sign
      vocabularies of between 0-50 words for 85% of the participants. It appears that
      sign learning by hearing parents of deaf children in this region needs to be
      actively promoted. The implications of these findings are discussed to address
      the communication needs of signing deaf children and their families within the
      South African context.

PMID- 11455820
TI  - Early identification of at-risk infants and toddlers: a transdisciplinary model
      of service delivery.
AB  - Traditional models of service delivery prevent speech-language therapists and
      audiologists from identifying and implementing early communication intervention
      (ECI) in South Africa. This study utilized the framework of the transdisciplinary
      team approach to develop a collaborative partnership between community nurses and
      speech-language therapists and audiologists. An interdisciplinary in-service
      training programme was implemented with 24 community nurses employed at family
      health clinics in Kwa-Zulu Natal; with the aim of enhancing their knowledge and
      attitudes toward the early identification and referral of at-risk children to
      speech-language therapists and audiologists. Three questionnaires were used to
      evaluate the nurses' knowledge and attitudes. Results indicated that the training
      programme significantly improved the nurses' knowledge regarding ECI but not
      their attitudes. Implications of these findings are discussed in terms of service
      delivery for ECI, and the education and training of early interventionists in the
      South African context.

PMID- 11455821
TI  - The current practices, training and concerns of a group of hospital-based speech
      therapists working in the area of dysphagia.
AB  - The aim of the study was to investigate the current practices, training, and
      concerns of a group of hospital-based speech therapists regarding the area of
      dysphagia practice. Questionnaires were posted to 75 speech therapists working in
      the major hospitals around Gauteng, Kwa-Zulu Natal and the Cape Province and
      responses were obtained from 50 therapists within the stipulated time. Closed
      ended questions were analysed quantitatively using descriptive statistics, while
      open-ended items were subjected to content analysis of themes articulated by
      respondents. Results indicated that the overwhelming majority of the respondents
      were involved in assessing and treating dysphagia patients. Specific problems
      faced by respondents included limited staff to share their workloads, large
      caseloads, restricted access to supervision/mentor systems and poor knowledge by
      other health personnel of their role in dysphagia. Almost half of the respondents
      also reported that they were involved in student training which included the area
      of dysphagia. Investigation of respondents' undergraduate and postgraduate
      training in dysphagia suggested that there were gaps in the theoretical content
      of these courses as well as a limited focus on practical training. Another
      finding was that respondents showed an awareness of the specific roles of the
      speech therapist in dysphagia intervention as well as the roles of the
      professionals constituting a multidisciplinary dysphagia team. Most of the
      respondents reported that they had access to dysphagia team members as well as to
      diet modification services. However, many of the respondents showed decreased
      knowledge of and awareness regarding accessibility of diagnostic procedures and
      suctioning methods used in dysphagia. The majority of the respondents rated their
      knowledge about specific theoretical areas as well as their counselling abilities
      to be better than their actual skills and confidence in assessing and treating
      dysphagia patients. Implications of the study included the need for clinicians,
      universities and professional organizations to work together to improve the
      existing situation.

PMID- 11455822
TI  - [The value of basic research as applied to cochlear implants].
AB  - This article discusses the value of basic research as applied to cochlear
      implants. The article is aimed at clinicians and audiologists who are working in
      the field of cochlear implants or who are interested in this field. The article
      also gives a more general introduction to modelling for researchers in the
      clinical environment. It provides an entry point to cochlear implant research and
      reviews the application of basic research to new developments in cochlear
      implants. It is shown what has been achieved so far and which problems still
      exist. The role of multidisciplinary research teams to solve these problems is
      discussed. Experimental research and modelling co-operate to solve problems and
      make new discoveries. The importance of modelling as a tool for basic research is
      emphasized.

PMID- 11455823
TI  - What do cochlear implants teach us about the encoding of frequency in the
      auditory system?
AB  - This article explores the coding of frequency information in the auditory system
      from the viewpoint of what has been learnt from cochlear implants. Cochlear
      implants may provide a window on central auditory nervous system function by
      creating the possibility to separate place and temporal information. An existing
      model of frequency discrimination in the acoustically stimulated auditory system
      is extended to include electrical stimulation. To be able to predict frequency
      difference limens for acoustic stimulation, an important assumption is that one
      spike per stimulus cycle is available, which may be provided by the existence of
      a volley principle. It is shown that to predict frequency difference limens for
      electrical stimulation of the auditory system, it must also be assumed that
      electrical stimulation causes desynchronization at a central auditory nervous
      system integration centre. With these assumptions, the model predicts the
      degradation in frequency discrimination that occurs for electrical stimulation.
      Finally, it is shown that cochlear implants have not yet proven conclusively that
      either rate-place coding or temporal coding is predominant in the auditory
      system.

PMID- 11455824
TI  - Use of the CID W22 as a South African English speech discrimination test.
AB  - South Africa currently lacks a pre-recorded South African English (SAE) specific
      speech discrimination test. In the absence of such a test, the SAE speaker
      recording (Tygerberg recording) of the American (USA) English (AE) CID W22
      wordlists--in combination with the original American CID W22 normative data--is
      the most widely used alternative. The reliability and validity of this method,
      however, has never been formally assessed. This study assessed the performance of
      15 normal hearing, female, first language SAE speakers on the first two full
      lists of Tygerberg CID W22 recording at 20, 30, 40, 50, 60 and 70 dBSPL, and
      compared their scores to the American CID W22 wordlist normative data. Overall,
      the South African subjects performed worse than the original American normative
      data at the lower presentation intensities (< 50 dBSPL). Use of the Tygerberg CID
      W22 recording--with the original American CID W22 normative data--for near
      threshold assessment of SAE speaking subjects was therefore concluded to be
      problematic. Use at suprathreshold intensities (> 40 dBSPL), however, was
      considered a viable option. These results reiterate the need for large scale,
      South African specific normative studies for the CID W22 wordlists if they are to
      continue their role as the dominant speech discrimination wordlists in South
      Africa.

PMID- 11455825
TI  - [An adequate use of PSA].

PMID- 11455826
TI  - [Prostatic intraepithelial neoplasm diagnosed with transrectal biopsy. Overall
      review].
AB  - OBJECTIVE: To review the incidence, clinical features and management guidelines
      for patients with isolated prostatic intraepithelial neoplasia (PIN) diagnosed
      through prostate transrectal biopsy. METHODS AND RESULTS: Search in Medline
      database for papers published between 1990 and 2000 based on the following key
      words: "prostatic intraepithelial neoplasia and needle biopsy". Nineteen papers
      fulfilling the search criteria were selected. CONCLUSIONS: The incidence of PIN
      in patients seen as part of an early diagnosis program is much lower than in
      patients attending standard Urology practices. PSA level and ultrasound changes
      are poor predictors of PIN presence in the biopsy. Prostate cancer incidence in
      successive biopsies ranges between 13.3% and 100%. None of the clinical variables
      used to diagnose prostate cancer (DRE, PSA and transrectal ultrasound) can
      predict accurately the existence of cancer associated to PIN, and only prostatic
      intraepithelial neoplasia grading is considered a good cancer predictor. There is
      no consensus with regard to diagnostic and therapeutic management in these
      patients.

PMID- 11455827
TI  - [Selective bladder sparing with transrectal resection of muscle-infiltrating
      tumors].
AB  - OBJECTIVE: To disclose te ability of TUR as monotherapy in muscle invasive
      bladder cancer. MATERIAL AND METHODS: 27 patients with muscle-invasive bladder
      cancer recruited throughout 1991-1999 were allocated into a protocol based on
      TUR. 30-45 days after the first TUR a second procedure was performed. The number
      of recurrences and progressions was registered. Progression-free survival and
      survival were analyzed using Kaplan-Meier estimates. RESULTS: Two patients were
      excluded due to persistence of muscle-invasive disease after the second
      resection. 8 subjects (32%) were lost in follow-up. 17 were eventually evaluable.
      12 patients (70.5%) had recurrences. Eventually, 4 more cystectomies were
      undertaken for invasive recurrences (4/17, 23.5%). During the study period, 3
      deaths were recorder (3/17, 17.6%). The actuarial probability of progression at
      93 months was estimated on 60%. CONCLUSIONS: 75% of patients retained their
      bladders. The proportion of patients lost in follow-up was very high. Patients
      must commit to a close surveillance.

PMID- 11455828
TI  - [PSA:alpha 1-antichymotrypsin ratio/total PSA in the diagnosis of prostatic
      cancer in the range of total PSA from 4 to 10 ng/ml].
AB  - OBJECTIVE: To evaluate the usefulness of the ratio PSA:alpha-1
      antichymotrypsin/total PSA (C/T) in the diagnosis of prostate cancer in the range
      of total PSA between 4 and 10 ng/mL. MATERIAL AND METHODS: By using home-made
      ELISAs we have determined plasmatic concentrations of total PSA and complex
      PSA:alpha-1-ACT in 300 patients with total PSA between 4-10 ng/mL. All samples
      were obtained before any manipulation that could interfere the PSA levels.
      RESULTS: By prostatic biopsy 85 patients (28.3%) were diagnosed of prostate
      cancer (CaP) and 215 (71.6%) of benign prostatic hyperplasia (BPH). The mean
      values of the complex PSA:alpha-1-ACT (4.2 ng/mL in the BPH patients vs 5.0 ng/mL
      in the CaP patients) and of the C/T ratio (0.70 vs 0.82, respectively) showed
      significant differences between both groups (p = < 0.0001). The total PSA did not
      show differences (6.1 ng/mL vs 6.0 ng/mL; p = 0.79). From all three parameter
      evaluated, the ratio C/T had the biggest area under the ROC (0.884) and
      statistically significant differences in comparison with total PSA (0.490; p = <
      0.001) and the complex PSA:alpha-1-ACT (0.696: p = < 0.001). Therefore, by using
      a ratio C/T > 0.62 to decide the performance of a biopsy, 27% of the patients
      with BPH could have avoided this procedure with a 100% sensitivity. Increasing
      the ratio to 0.68 the specificity is 47% and the sensitivity is 95.2%. Rectal
      examination did not have influence on the cut-off, sensitivity, specificity and
      area under the ROC of the ratio C/T. CONCLUSIONS: Our results confirm that the
      ratio C/T improve the diagnostic capacity of the total PSA between 4-10 ng/ml.
      Moreover, the rectal examination does not influence the selection of ratio C/T
      cut-off suggestives of CaP neither the diagnostic efficacy.

PMID- 11455829
TI  - [Incidental diagnosis of renal carcinoma. Does it imply a better prognosis?].
AB  - OBJECTIVE: We present 267 patients undergoing surgery for renal carcinoma,
      comparing the incidental tumour and symptomatic tumour with different parameters
      and evaluating the prognostic significance of the incidental diagnosis. MATERIAL
      AND METHODS: Of the 267 patients, 110 (41.2%) were diagnosed incidentally. The
      different variables analysed were: age, sex, tumour size, if unilateral or
      bilateral, histological type, stage, degree of cellular differentiation and
      survival. The mean follow-up period was of 43.32 mos in the symptomatic patients
      and 41.85 mos in the patients diagnosed incidentally. The data obtained was
      analysed with the SPSS statistic pack. RESULTS: No significant difference was
      detected between both groups in regards to age, sex, if unilateral or bilateral
      and histological type. Comparing tumour size, a statistic difference was observed
      with slices at 6 cm. When analysing the stage and degree of cellular
      differentiation, a significant difference is found with tumours diagnosed
      incidentally presenting better differentiation and a lower stage at the moment of
      diagnosis. Survival after 5 yrs was of 65.7% for symptomatic patients in
      comparison to 81.7% for the incidental group, which implies high statistical
      signification (log rank = 0.0018). CONCLUSIONS: In our series no significant
      differences were detected between incidental and symptomatic tumours when
      comparing age, sex, anatomic side and histological type. Significant differences
      were indeed detected in relation to size, degree of cellular differentiation,
      tumour stage and survival.

PMID- 11455830
TI  - [Prognostic value of DNA ploidy in prostatic cancer].
AB  - OBJECTIVE: To asses the prognostic value of deoxyribonucleic acid (DNA) ploidy in
      a group of patients with prostate cancer treated with adrogenic blockade.
      MATERIALS AND METHODS: A retrospective study on 136 patients with prostatic
      cancer having undergone androgenic blockade was carried out. The prognostic
      influence of age, T and M categories, Gleason score and flow cytometry-determined
      DNA ploidy from survival analyses. Univariate survival analysis was carried out
      following Kaplan-Meier's method, while for multivariate survival analysis Cox's
      proportional hazard model was used. RESULTS: The univariante analysis showed that
      T and M categories, Gleason score and DNA ploidy have prognostic value. The Cox's
      regression analysis identified DNA ploidy, metastasis and Gleason score as
      independent variables having prognostic potential. CONCLUSIONS: DNA ploidy has
      independent prognostic value in prostate cancer treated with androgenic blockade
      and improves the predictive potential of classical prognostic factors.

PMID- 11455831
TI  - [Spontaneous extraperitoneal bladder rupture. Report of a case].
AB  - The spontaneous extraperitoneal bladder rupture is an uncommon event and the
      diagnosis is very difficult. It is defined like the rupture of bladder wall in
      absence of traumatism or iatrogenic techniques. The extravasation usually is
      produced into the peritoneal cavity, because of the greater weakness of the
      vesical dome. The diagnosis is based on the retrograde cystography, being
      necessary the surgical treatment in the intraperitoneal rupture, while the
      extraperitoneal one, could be treated in a conservative way with a vesical
      catheter. Here we present a case of spontaneous extraperitoneal bladder rupture,
      with oliguria, abdominal pain and a right hypochondrius mass as clinic
      presentation. Due to this, the diagnosis was made by the TAC, in which it was
      appreciated a continuity solution in the anterior bladder wall, with a contrast
      extravasation through the anterior abdominal wall. The retrograde cystography
      confirmed the definitive diagnosis. The treatment followed was based on the
      keeping of the vesical catheter and antibiotherapy.

PMID- 11455832
TI  - [Thrombosis of the renal artery secondary to closed abdominal trauma].
AB  - We report a case of female 24 years old who had a blunt abdominal trauma. The
      immediate consequence was the radiological evidence of a left kidney abolition,
      secondary to a renal artery thrombosis. The treatment was conservative, and there
      was not a surgical procedure.

PMID- 11455833
TI  - [Testicular dislocation. Report of 2 new cases and review of the literature].
AB  - We report 2 new cases of testicular luxation. A review of current literature is
      made. Testis was located inguinal after scrotal trauma in both cases. Early close
      reduction was unsuccessfully. A delayed reduction was found in one case at the
      moment of surgery. A surgical replacement of the testis was carried out in the
      other patient. Follow-up control revealed a benign course in both. Testicular
      dislocation is a rare complication after scrotal trauma (only 152 cases
      reported). Physician have to be aware of this possibility following perineal
      trauma. Oftenly, a surgery reduction is required.

PMID- 11455834
TI  - [Total androgenic insensitivity syndrome. Presentation as giant inguinal mass].
AB  - The androgen insensitivity syndrome is the most frequent form of masculine
      psedohermafroditism. The affected patients present female phenotype without
      sexual ambiguity but with karyotype 46 XY. In this syndrome the frequency of
      malignizacion of the testicles increases progressively with the age, because of
      this, the importance of an earlier diagnosis. We present a case of later
      diagnosis late of the androgen insensitivity syndrome, that debut with a great
      inguinal mass.

PMID- 11455835
TI  - [Nephrogenic adenoma of the bladder: metaplasia or embryologic alteration?].
AB  - OBJECTIVES: To present a new case of nephrogenic adenoma of the bladder and to
      review the current concepts on the etiopathogenesis of this lesion. CLINICAL
      CASE: Seventy years old female with repetitive haematuria who was diagnosed as
      having a nephrogenic adenoma of the bladder which was extirpated by cold biopsy
      forceps. No tumoral relapse was detected after 16 months of follow up.
      DISCUSSION: In the light of the present knowledges, the origin of nephrogenic
      adenoma is a phenomenon of urothelial metaplasia due to a chronic irritative
      stimulus wich would lead a cellular proliferation with potentialities to
      originate mesonephric tissues and which starting point could be on not completely
      involutioned mesonephric cellular rests and/or on de-differentiated mature
      urothelial cells.

PMID- 11455836
TI  - [Signet ring-cell adenocarcinoma in colocystoplasty].
AB  - We report a case of signet ring-cell adenocarcinoma in augmentation
      colocystoplasty. We review the current literature about tumours developing in
      augmentation bladder.

PMID- 11455837
TI  - [Giant inguino-scrotal hernia of the bladder. Clinical case and review of the
      literature].
AB  - Bladder hernia is an uncommon condition with a frequency between 0.5 and 3%,
      reaching the 10% between patients older than 50 years. It's more predominant in
      males aged between 50 and 70. The diagnosis usually happens in the course of
      surgical repair of inguinal hernias, because the bladder hernia has no specific
      clinical findings. Management includes the resection or reduction of the bladder
      hernia, with de-obstruction of the lower urinary tract, if present, and repairmen
      of inguinal path. We report a new case and review the literature.

PMID- 11455838
TI  - [Continuing education grant in urology of the Galician Society of Urology: report
      on a visit to the Scottish Lithotriptor Centre in Edinburgh, United Kingdom].

PMID- 11455839
TI  - [In reference to the paper "Intracranial metastasis in cancer of the prostate].

PMID- 11455840
TI  - [Vandellia cirrhosa, poorly known urologic parasite].

PMID- 11455841
TI  - [Urinoma: unusual complication of recurrent rectal adenocarcinoma].

PMID- 11455842
TI  - Secondary prevention in patients several years after myocardial infarction:
      comparison of an outpatient and an inpatient rehabilitation programme.
AB  - OBJECTIVE: To compare the effectiveness of secondary preventive measures in
      patients after myocardial infarction participating in an outpatient
      rehabilitation programme at a university hospital with those of an inpatient
      programme in community hospitals. DESIGN: Cross-sectional study of patients
      several years after myocardial infarction. METHODS: Seven hundred patients who
      survived myocardial infarction in the period from 1 January 1989 to 31 December
      1995 were chosen from archives of the university hospital (350 patients) and from
      archives of two community hospitals (350 patients). The patients from the
      university hospital attended an outpatient rehabilitation programme, while the
      patients from the community hospitals attended an inpatient rehabilitation
      programme. The data were obtained by questionnaire, clinical examination and
      laboratory blood analyses. RESULTS: One hundred and eighty patients attending an
      outpatient and 140 patients attending an inpatient rehabilitation programme
      responded to the invitation. Among those who were smokers at the time of
      myocardial infarction, 91% of patients from the outpatient programme versus 77%
      of patients from the inpatient programme (P < 0.05) gave up smoking and were
      still non-smokers; 69% versus 48% (P < 0.05) had a lipid-modified diet; 21%
      versus 36% (P < 0.05) were obese (BMI > 30 kg/m2). Blood pressure > 140/90 mmHg
      was found in 21% versus 58% (P < 0.05); total cholesterol > 5.0 mmol/l in 67%
      versus 87% (P < 0.05); and fasting glucose > 5.6 mmol/l in 43% versus 63% (P <
      0.05) of patients from the outpatient and the inpatient programmes, respectively.
      Among prophylactic drug treatments higher usage of beta-blocking agents (56%
      versus 36%; P < 0.05) and lipolytic agents (43% versus 23%; P < 0.05) and no
      significant difference in usage of antiplatelet drugs (83% versus 75%) and
      angiotensin-converting enzyme inhibitors (30% versus 32%) was found in patients
      from the outpatient programme compared to patients from the inpatient programme.
      Only regular physical activity was performed better by patients from the
      inpatient programme than by patients from the outpatient programme (68% versus
      50%; P < 0.05). CONCLUSIONS: The outpatient rehabilitation programme of the
      university hospital resulted in better application of secondary prevention than
      the inpatient rehabilitation programme of community hospitals.

PMID- 11455843
TI  - Pharmaco-economic impact of HMG-CoA reductase inhibitors in type 2 diabetes.
AB  - Dyslipidemia is very common in diabetics and substantially increases the risk of
      fatal and non-fatal cardiovascular disease. Pharmacological therapy with 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') is
      effective for dyslipidemia, but the cost and efficacy of individual therapies
      vary. Therefore, the interest in cost-effective pharmacologic interventions for
      the prevention of cardiovascular disease events in diabetics has increased. In
      this article, the literature pertaining to the epidemiology, cost and efficacy of
      statins in preventing cardiovascular disease in patients with type 2 diabetes
      mellitus, in both the primary and secondary prevention settings, is reviewed.
      Cost-effectiveness studies of statins in the diabetic population are detailed,
      along with recommendations for further research.

PMID- 11455844
TI  - Coronary calcification and cardiac events after percutaneous intervention in
      dialysis patients.
AB  - BACKGROUND: Previous studies have described increased vascular calcification in
      renal dialysis patients. The clinical significance of this finding with respect
      to outcomes after percutaneous coronary intervention in this population is
      unknown. METHODS: We analysed a prospective interventional database at a single
      tertiary center and identified 41 dialysis patients who underwent coronary
      angioplasty. All studies were reviewed for the presence of coronary calcium in
      the target and reference vessels and compared with respect to baseline clinical
      factors and cardiovascular outcomes. RESULTS: The mean ages for those with and
      without coronary calcification were 63.6 +/- 11.0 and 67.3 +/- 11.0,
      respectively, P = 0.30. The groups were similar in years on dialysis, diabetes,
      hypertension, smoking, and measures of calcium and phosphate balance. The total
      cholesterol, LDL-C, HDL-C, and triglycerides were 162.5 +/- 42.3 and 202.0 +/-
      54.5, P = 0.02; 94.9 +/- 39.6 and 121.2 +/- 48.1, P = 0.18; 39.3 +/- 12.4 and
      47.3 +/- 12.2, P = 0.15; 157.4 +/- 100.4 and 181.3 +/- 187.4, P = 0.15, for those
      with and without calcification, respectively. The composite of target vessel
      revascularization, myocardial infarction, or death was 47.4% and 77.3% for those
      with and without calcification, respectively, P = 0.06. The Cox proportional
      hazards model, controlling for years on dialysis, showed a significant, event
      free survival in those with coronary calcium seen fluoroscopically, P = 0.05.
      CONCLUSIONS: In dialysis patients, coronary calcification identified in the
      target or reference vessels is associated with lower total cholesterol and
      favourable interventional outcomes.

PMID- 11455845
TI  - Is microalbuminuria an integrated risk marker for cardiovascular disease and
      insulin resistance in both men and women?
AB  - BACKGROUND: Microalbuminuria is associated with some cardiovascular risk factors.
      However, it is presently unclear whether microalbuminuria is associated with
      other cardiovascular risk factors and markers of insulin resistance in both men
      and women. DESIGN: The baseline parameters of the on-going prospective D.E.S.I.R.
      Study (Data from an Epidemiological Study on the Insulin Resistance syndrome)
      were analysed. METHODS: The subjects (n = 3878, age 30-64) had a medical and
      biological checkup including arterial pressure, ECG, lipids, haematocrit,
      leukocyte count, insulin and urinary albumin concentration. RESULTS: Arterial
      pressure was significantly higher in microalbuminuric than in normoalbuminuric
      men and women. The heart rate and the prevalence of smoking were higher in
      microalbuminuric than in normoalbuminuric men, but not in women. Total- and LDL
      cholesterol, triglycerides, apolipoprotein-B, leukocyte count, uric acid,
      haematocrit, haemoglobin and red cell volume were greater in microalbuminuric
      than in normoalbuminuric men. Total- and HDL-cholesterol were lower whereas
      triglycerides and uric acid were significantly greater in microalbuminuric than
      in normoalbuminuric women. The 9-year calculated absolute cardiovascular risk was
      higher in microalbuminuric than in normoalbuminuric men (4.18% vs. 2.79%,
      respectively, P < 0.0001) but was similar in women (0.75% vs. 0.69%,
      respectively, NS). Fasting blood glucose and insulin were higher in
      microalbuminuric than in normoalbuminuric men, but not in women. A multiple
      regression showed that microalbuminuria was associated with systolic arterial
      pressure, fasting glucose, leukocyte count and haematocrit in men, and with
      systolic arterial pressure and triglycerides in women. CONCLUSIONS:
      Microalbuminuria is associated with most cardiovascular risk factors and markers
      of insulin resistance in men, but no consistent association is observed in women.
      The determinants of microalbuminuria appear different in men and women,
      suggesting a different pathophysiology and perhaps significance of
      microalbuminuria in men and women.

PMID- 11455846
TI  - Early onset of androgenetic alopecia associated with early severe coronary heart
      disease: a population-based, case-control study.
AB  - CONTEXT: The relationship of ischaemic heart disease (IHD) with androgenic
      alopecia (AGA) has been demonstrated, but no differentiation between early and
      late onsets of alopecia with regard to the risk and severity of IHD has been
      made. OBJECTIVE: To test if the early onset of alopecia is a risk factor for
      early severe, coronary artery disease (CAD) requiring surgery and to test if the
      early onset of AGA differs in this respect from the late onset of AGA. DESIGN:
      Population-based case-control study. SETTING AND PARTICIPANTS: All the 85 male
      persons living on 31 December 1999 in a Finnish town with total population of
      7200, who had had a coronary revascularization procedure between March 1987 and
      January 1999, were drawn from the discharge register. For each case, an
      individually selected age-matched control person living in the same town was
      drawn from the official census register. MAIN OUTCOME MEASURE: Alopecia defined
      as grade 3 vertex or more on the alopecia classification scale of Hamilton,
      modified by Norwood South Med J, 68:1359-1365, 1975. RESULTS: The unadjusted odds
      ratio (OR) for coronary revascularization under the age of 60 years was 3.57 (95%
      confidence interval (CI) 1.19-10.72) in men with an early onset of AGA compared
      with men with normal hair status or late AGA. After multivariate adjustment for
      the traditional CAD risk factors, the corresponding OR was 3.18 (95% CI, 1.01
      10.03). The unadjusted OR for the coronary revascularization procedure at any age
      was 2.14 (95% CI, 1.08-4.23) in the subgroup of the men with early AGA compared
      to those with late AGA or normal hair status. After adjustment for traditional
      risk factors this OR was 1.84, being nearly significant (95% CI, 0.90-3.77).
      CONCLUSION: Our results support the hypothesis that the early onset of AGA is a
      risk factor for an early onset of severe coronary heart disease.

PMID- 11455847
TI  - Cardiac rehabilitation after coronary artery bypass surgery: 10-year results on
      mortality, morbidity and readmissions to hospital.
AB  - AIM: To evaluate the long-term secondary preventive effect of a comprehensive
      rehabilitation programme after coronary artery bypass grafting (CABG). METHODS:
      The study group included 49 consecutive patients who underwent bypass surgery and
      were then offered a rehabilitation programme consisting of education in risk
      factor control, a physical training programme and regular follow-up at a post
      CABG clinic. The control group (n = 98), consisting of two well-matched CABG
      patients for each study patient, was offered the usual care with no access to a
      cardiac rehabilitation programme. The two groups were followed for 10 years and
      the results regarding cardiovascular mortality, morbidity, total cardiac events
      and readmissions to hospital were compared. RESULTS: The total mortality (study
      group 8.2%, control group 20.4%) and cardiovascular mortality (8.2 versus 15.3%)
      after 10 years did not differ significantly between the groups. In the study
      group, nine patients (18.4%) had 10 cardiac events (four cardiovascular deaths,
      five non-fatal myocardial infarctions and one CABG) compared to 34 patients
      (34.7%, P < 0.05) suffering 46 (P < 0.01) cardiac events (15 cardiovascular
      deaths, 18 non-fatal myocardial infarctions, eight CABG, five coronary
      angioplasties) in the control group. The number of readmissions to hospital (2.1
      versus 3.5 per patient) and length of admissions (11 versus 26 days per patient)
      was significantly lower in the study group (P < 0.01). CONCLUSION: A
      comprehensive cardiac rehabilitation programme offered to patients after coronary
      artery bypass surgery will improve the long-term prognosis and reduce the need
      for hospital care.

PMID- 11455848
TI  - The association between deaths from myocardial infarction and household size in
      England and Wales.
AB  - BACKGROUND: Chronic infection with organisms such as Chlamydia pneumoniae is
      thought to cause coronary heart disease. We investigated whether myocardial
      infarction deaths are associated with large household size and overcrowding, as
      these are factors that may facilitate the transmission of infection. DESIGN:
      Ecological study of England and Wales. METHODS: Population data were obtained
      from the 1991 National Census and mortality data were obtained from the Office of
      National Statistics. For various categories of household size and overcrowding,
      we calculated mortality rates standardized for age, sex and deprivation. RESULTS:
      Standardized mortality rates for acute respiratory infections were associated
      with household size and overcrowding, while rates for myocardial infarction and
      gastric carcinoma, both putatively associated with chronic infection, were
      associated with household size. For combined deaths from causes other than
      myocardial infarction, there were small associations with household size and
      overcrowding. In the case of myocardial infarction, the association was generally
      strongest in the age group 45-54.9 years. For this age group, the standardized
      mortality rate ratio for the category of largest size household was 2.7 in the
      year 1991. CONCLUSIONS: There is an association between household size and
      mortality from myocardial infarction. Chronic infection is a possible cause.

PMID- 11455849
TI  - Blood lipid levels in a rural male population.
AB  - OBJECTIVES: Farmers have a low risk for cardiovascular disease, which may be
      related to a favourable blood lipid profile. In order to study the blood lipid
      levels and evaluate the effect of other cardiovascular risk factors on the blood
      lipid profile, this cross-sectional study was made. MATERIAL AND METHODS: A total
      of 1013 farmers and 769 non-farming rural men in nine different Swedish counties
      were examined, interviewed, and replied to questionnaires. The inter
      relationships between different risk factors were analysed using a multivariate
      linear regression model. RESULTS: The farmers had a significantly more favourable
      blood lipid profile than the non-farmers although the total cholesterol levels
      were almost the same for the two groups. In the total study population there were
      significant positive relationships between total cholesterol level and body mass
      index (BMI), diastolic blood pressure and smoking. The high-density lipoprotein
      (HDL) level was positively related to physical workload and alcohol consumption,
      and negatively related to BMI, waist/hip ratio and smoking. Triglyceride levels
      showed a positive relationship to BMI, waist/hip ratio and blood pressure.
      Differences between farmers and other rural males were seen, especially with
      respect to the effect of physical activity and psychosocial factors. Among the
      farmers, a negative correlation between the Karasek-Theorell authority over work
      index and total cholesterol, the low-density lipoprotein (LDL)/HDL ratio and
      triglyceride levels was observed. CONCLUSIONS: This study indicated that diet is
      of minor significance for the blood lipid profile, whereas factors such as
      physical activity, body weight and the waist/hip ratio, smoking, alcohol
      consumption, and perhaps psychosocial working conditions are major independent
      factors affecting the blood lipid profile most prominently among farmers, but
      also among non-farming rural men.

PMID- 11455850
TI  - The impact of emotions on coronary heart disease risk.
AB  - BACKGROUND: Coronary heart disease is now well recognized as a psychosomatic
      illness. Emotional disturbance increasingly appears to have an impact on both the
      development of coronary artery disease over time and the precipitation of acute
      coronary heart disease events. METHOD: This descriptive review is based on
      systematic literature reviews from 1980 to 2000 with an emphasis on predictive
      and prospective studies. RESULTS: The empirical evidence linking emotional
      disturbances such as anxiety, depression and anger to coronary heart disease is
      now robust. There is also increasing evidence for the underlying pathophysiology
      that may link emotions to coronary heart disease. CONCLUSIONS: Emotional
      disorders and coronary artery disease commonly coexist. Emotional disorders often
      follow events of coronary heart disease. Prospective studies, however, now show
      that emotional disturbance is also a significant risk factor for coronary artery
      disease and especially in those with pre-existing disease. It is important both
      to diagnose emotional disorders early in coronary heart disease patients and
      implement effective treatments with the likelihood of reducing subsequent
      morbidity and mortality.

PMID- 11455851
TI  - Combination therapies for systemic sclerosis.

PMID- 11455852
TI  - Therapy of Sjogren's syndrome.

PMID- 11455853
TI  - Spondylarthropathies: options for combination therapy.

PMID- 11455854
TI  - Combination therapy in rheumatoid arthritis.

PMID- 11455855
TI  - What will treatment of autoimmune diseases entail in 2010?

PMID- 11455856
TI  - Stem cell transplantation for autoimmune diseases.

PMID- 11455857
TI  - Combination treatment in autoimmune diseases. Methodology of combination trials.
AB  - Even with the limited number of antirheumatic agents available, theoretical
      considerations lead to an almost infinite number of combination strategies. This
      article outlines possible strategies based on the primary choice between
      maximization of efficacy or minimization of toxicity. Strategies are illustrated
      with examples from trial experience in the field of rheumatoid arthritis.

PMID- 11455859
TI  - Regulatory aspects of evaluating combination treatments in autoimmune diseases.

PMID- 11455860
TI  - New therapies in development for autoimmune diseases: their rationale for
      combination treatment.

PMID- 11455861
TI  - Combination therapy for autoimmune diseases: the rheumatoid arthritis model.

PMID- 11455862
TI  - Combination therapy: the risks of infection and tumor induction.
AB  - It is clear that the rate of infection is increased in most of the more serious
      forms of autoimmune disease and agents such as high-dose steroids and the
      alkylating agents increase this risk. Other agents such as MTX, CsA, LEF, AZA and
      the TNF antagonists do not appear to increase the risk of infection given either
      alone or in combination. Similarly, the risk of malignancy in certain types of
      autoimmune disease appears increased. However, other than the alkylating agents,
      none of the agents used appear to increase this risk. The more recently released
      agents such as CsA, LEF and the TNF antagonists need longer durations of follow
      up to substantiate this, however. It is clear that, unless they are absolutely
      necessary, one should avoid the alkylating agents used either alone or in
      combination to avoid problems with infection and malignancy. In addition, the use
      of steroids should be kept as low as possible to avoid infections. It is possible
      that the use of the more benign agents alone and in combination earlier in the
      disease course may help to reduce both infection and the incidence of malignancy
      in the long run.

PMID- 11455863
TI  - Combination treatment in autoimmune diseases: systemic lupus erythematosus.

PMID- 11455864
TI  - Combination therapy in autoimmune disease: vasculitis.

PMID- 11455865
TI  - [Heart rate variability in anesthesia].
AB  - Measurement of heart rate variability (HRV) in the perioperative period is not
      yet part of routine monitoring. Because of a lack of standardization, comparison
      of results of different investigations is difficult. Caution is needed in
      interpreting data of HRV measurements because of the complexity of autonomic
      control of the cardiovascular system. Moreover, confounding effects of multiple
      factors influencing HRV in the perioperative setting make interpretation of data
      difficult and limit this methodology, for example, as a depth-of-anaesthesia
      monitor. HRV reflects the response of the heart to a variety of influences. None
      of the parameters obtained, however, elucidates directly the mechanism or site of
      action of an anaesthetic drug. Knowledge of the pathophysiology underlying HRV is
      critical in order to understand the state of the autonomic nervous system and its
      relevance for patient management. Nevertheless, previous studies show that HRV
      can provide information about sympathetic and parasympathetic influences
      affecting the cardiovascular system in the perioperative period. Thus, HRV seems
      to be a useful tool for preoperative cardiovascular risk stratification. Of major
      concern in this context is the quality of the recording of the electrocardiogram
      when assessing HRV. Because of the ongoing progress in monitoring with regard to
      acquisition and computer-based analysis of HRV data, it seems at least possible
      to measure HRV routinely in the perioperative setting. However, the need for
      standardization requires large prospective and standardized trials. Depending on
      the results, the clinical relevance of HRV as a relatively simple and non
      invasive perioperative monitoring has to be re-evaluated.

PMID- 11455866
TI  - [Rocuronium or vecuronium for intubation for short operations in the preschool
      age? Effects on time in the operating room and postoperative phase].
AB  - This prospective randomized study compares the effects of rocuronium (R) and
      vecuronium (V) on the early postoperative period in infants. Forty-eight infants
      between the ages of three and six, scheduled for elective ENT procedures, were
      studied after prior approval of local ethics committee and informed parental
      consent. All children were premedicated with chlorprotixene and belladonna.
      Anaesthesia was induced with 5 mg/kg thiopentone and 1 vol.-% halothane.
      Subsequently, 0.4 mg/kg rocuronium or 0.075 mg/kg vecuronium were administered,
      respectively. Anaesthesia and post-operative care were conducted by independent
      anaesthetists, who were unaware of the drug used and of the relaxometric data
      obtained. All children were monitored in the recovery room by pulse oximetry
      until they reached a Steward Score of 6. Demographic data did not differ between
      the groups. No differences were recorded between the non-depolarizing relaxants
      regarding intubation time (R: 24.1 +/- 4.2 min, V: 25.8 +/- 6.8 min) and the time
      interval from end extubation to leaving the operating theatre (R: 2.3 +/- 0.8
      min, V: 2.6 +/- 1.2 min), respectively. Similarly, no differences in SaO2 were
      noted during the recovery period in the recovery room. Significant differences
      between the non-depolarizing relaxants were found in the TOF-ratios at extubation
      (R: 0.73 +/- 0.31 min, V: 0.48 +/- 0.34 min) and arrival in the recovery room (R:
      0.88 +/- 0.21 min, V: 0.69 +/- 0.26 min). 0.4 mg/kg Rocuronium and 0.075 mg/kg
      vecuronium can be used for intubation during short operations on pre-school
      children. Rocuronium may be the better alternative, due to its faster
      neuromuscular recovery properties.

PMID- 11455867
TI  - [Postoperative nausea and vomiting--still a problem?].
AB  - Based on a questionnaire of the General Hospital of Hamburg-Altona, we asked 738
      patients about postoperative complaints such as nausea, vomiting, pain in the
      operating field and feeling of coldness in order to record the quality of the
      results of operation and anaesthesia in 1997 and 1998. The incidence of nausea
      and vomiting amounted to only 29% on average. One of our earlier studies of
      postoperative vomiting from 1995-1997 and the results gained from a control group
      of non-treated patients in our ondansetron study from 1995, which was conducted
      using information drawn from the routinely-used anaesthesia protocol and was
      therefore limited to data from the immediate pre- and postoperative period up to
      discharge of the patients from the recovery ward, showed much higher frequencies
      of nausea and vomiting (44 and even 66% on average, respectively). We cannot
      definitely evaluate whether the reduction in the average rates of nausea and
      vomiting in our present study is due to the additional preoperative application
      of 150 mg vomex supp. and 1.0-2.5 mg dehydrobenzperidol and/or 20-30 mg
      metoclopramid given i.v. shortly before the end of anaesthesia or to more
      intensive observation of non-medicinal prophylactic possibilities. But when we
      look at the frequency of nausea and vomiting in special groups of our present
      study, we can still find unacceptably high rates of nausea and vomiting, for
      instance 40% after cholecystectomies and abruptios and even 50% after struma
      operations. This shows that a satisfactory solution to this problem has not yet
      been found--partly due, unfortunately, to financial restrictions. Nevertheless,
      for 15% of the patients postoperative nausea and vomiting were of only minor
      importance for general satisfaction with the treatment given them. This was
      probably due to good premedication of amnestic after-effects of narcosis.

PMID- 11455868
TI  - [Delirium due to urinary retention: confusing for both the patient and the
      doctor].
AB  - A delirium due to urinary retention confuses both patient and physician. Three
      patients presented with delirium and/or physical deterioration had a bladder
      retention. A man aged 82 had delirium and an acute renal failure due to a urinary
      retention with an enlarged prostate gland. A woman aged 81 had a delirium and a
      bladder retention due to an atonic bladder. A man aged 71 showed cognitive
      deterioration and a bladder retention due to a backbone-fracture and faecal
      impaction. In the elderly it is very important to include urinary retention in
      differential diagnosis because its presentation can be atypical.

PMID- 11455869
TI  - [Late-life depression and subcortical ischemic white matter lesions].
AB  - Late-life depression and cerebral ischemic white matter lesions. Interest in
      cerebrovascular disease as a risk factor for depression in the elderly has grown
      in the last few years. Some authors recently have proposed the concept of a
      'vascular depression'. In this paper, which presents a selective review of the
      literature, it is argued that 'vascular depression' is not a nosological entity.
      However, it has been shown that cerebral white matter lesions, identified using
      Magnetic Resonance Imaging (MRI) and thought to represent ischemic damage, are
      related to depression in the elderly. In particular, there is a correlation with
      late-onset depression. Moreover, these white matter lesions in depressed elderly
      adults are associated with cognitive impairment, and probably also with a
      relatively poor response to treatment.

PMID- 11455870
TI  - [Consensus on the concepts of cortical, subcortical and frontal dementia.
      Research by national and international dementia experts].
AB  - The level of agreement concerning the concepts cortical, subcortical and frontal
      dementia. The level of agreement between experts in the field of dementia
      concerning cortical, subcortical and frontal dementia was established. Nowadays
      these syndromes are implemented in clinical practice; the discussion about the
      validity and reliability of these concepts however has diminished. Forty-one
      national and international dementia experts of four disciplines completed a
      questionnaire, based on the cognitive section of the CAMDEXR. For each syndrome
      they marked whether the cognitive function mentioned was impaired or unimpaired
      in cortical, subcortical and frontal dementia. The level of agreement between
      experts was determined by use of a derivative of the kappa-coefficient. Cortical
      dementia was characterised by high levels of agreement between the experts. With
      an observed level of agreement of 0.76, experts reached the highest consensus
      about this syndrome. Less agreement was observed in the judgements of subcortical
      and frontal dementia, with observed levels of agreement of 0.64 and 0.67
      respectively. No differences were found in the assessments of national and
      international experts, as well as between the participating disciplines.
      Apparently, the application of these syndromes in clinical practice is difficult.
      Because of this confusion the practical meaning is limited, and one may wonder
      wether these concepts must still be used in clinical practice.

PMID- 11455871
TI  - [The role of observer for the reliability of Dutch version of the Discomfort
      Scale-Dementia of Alzheimer Type (DS-DAT)].
AB  - The role of the observer in the reliability of the Dutch Discomfort Scale
      Dementia of Alzheimer Type (DS-DAT). The Discomfort Scale of Dementia of the
      Alzheimer Type (DS-DAT) is an instrument to assess discomfort in severely
      demented patients. No data on the reliability of assessment using a Dutch
      translation were available. In this paper, we analyse the role of the observer in
      the reliability of rating. This is of importance for studies in which many
      physicians perform multiple assessments. Twenty-eight nursing home physicians in
      training rated the DS-DAT in five nursing home patients with dementia presented
      on videotape. This was repeated after five months. All the physicians were
      previously trained in the use of the instrument. The results were statistically
      analysed using random effects analysis of variance. The Intra-class Correlation
      Coefficient (ICC) was 0.74 for inter-observer reliability and 0.97 for intra
      observer reliability. Variance between subsequent assessments was small, but
      physicians appeared to differ somewhat among themselves in the way they rated the
      videotaped patients. A future complete reliability assessment of rating the DS
      DAT in clinical practice would involve patient variation as well, scoring
      patients in clinical practice.

PMID- 11455872
TI  - [Geriatrics--from a nursing home doctor to specialty].

PMID- 11455873
TI  - [Reproduction and development in flowering plants].
AB  - Why mark the centenary of the independent discovery of double fertilization by
      Sergius Nawashin (1898) and Leon Guignard (1899), when biology has progressed so
      much since the beginning of the XXth century? This discovery still constitutes
      one of the key references in plant biology: double fertilization is unique to
      flowering plants among all living organisms. This meeting is also the occasion to
      associate angiosperm fertilization with developmental biology because of the
      localization of this event in the flower. Very important and significant progress
      has been made in elucidating flower development during the last ten years. And
      today it is possible to understand the diversity of floral structure present in
      the angiosperms in the context of a underlying mechanism of flower development
      inherited from their common ancestor. This special issue also allows a survey of
      these two broad scientific fields, plant reproduction and plant development
      (flower and embryo). It might also attract new, talented young scientists.

PMID- 11455874
TI  - Goethe and the ABC model of flower development.
AB  - About 10 years ago, the ABC model for the genetic control of flower development
      was proposed. This model was initially based on the analysis of mutant flowers
      but has subsequently been confirmed by molecular analysis. This paper describes
      the 200-year history behind this model, from the late 18th century when Goethe
      arrived at his idea of plant metamorphosis, to the genetic studies on flower
      mutants carried out on Arabidopsis and Antirrhinum in the late 20th century.

PMID- 11455875
TI  - Molecular and evolutionary analysis of a plant Y chromosome.
AB  - Plants have evolved a great diversity of sex determination systems. Among these,
      the XY system, also found in mammals, is one of the most exciting since it gives
      the opportunity to compare the evolution of sex chromosomes in two different
      kingdoms. Whereas genetic and molecular mechanisms controlling sex determination
      in drosophila and mammals, have been well studied, very little is known about
      such processes in plants. White campion (Silene latifolia) is an example of plant
      with X and Y chromosomes. What is the origin of the X and Y chromosomes? How did
      they evolve from a pair of autosomes? In our laboratory, we have isolated the
      first active genes located on a plant Y chromosome. We are using them as markers
      to trace the origin and evolution of sex chromosomes in the Silene genus.

PMID- 11455876
TI  - Self-incompatibility in flowering plants: the Brassica model.
AB  - Self-incompatibility (SI) is a widespread mechanism in flowering plants that
      prevents self-fertilization. Self-pollen recognition relies on the products of
      genes located at the S (self-incompatibility) locus. Significant progress towards
      understanding molecular interactions allowing stigmatic cells to recognize and
      reject self-pollen in Brassica has been made during the past two years. Thus, the
      male and female determinants responsible of the self-incompatibility (SI)
      response have been identified. The structural features of these molecules
      strongly suggest that SI response is triggered by a ligand-receptor interaction.

PMID- 11455877
TI  - Male sterility in plants: occurrence, determinism, significance and use.
AB  - Most of higher plant species are hermaphroditic and male-sterility is often
      considered as an accident of development. In fact among the multiple possible
      causes of male-sterility, the most frequently met in nature is cytoplasmic male
      sterility (cms) which is a maternally inherited trait playing an active role in
      the evolution of gynodioecious species. Recent molecular studies have shown that
      this trait is determined by additional genes created in plant mitochondrial
      genomes due to their high recombinogenic activity. The physiological mechanisms
      by which the products of these genes interfere with the formation of male
      gametophytes are still the subject of intense research.

PMID- 11455878
TI  - Double fertilization in flowering plants: discovery, study methods and
      mechanisms.
AB  - The double fertilization of flowering plants was discovered a century ago. The
      cytology of the gametes is now well known. However the description of the
      fertilization steps is still poor and most of the cellular and molecular
      mechanisms involved are unknown. Recent research using in vitro fertilization
      demonstrated that the early steps of fertilization share some homology with those
      in animal species. In particular, gamete fusion is followed by a cytosolic
      calcium increase in the fertilized egg as well as a calcium influx. Further
      understanding of fertilization also comes from the analysis of mutants isolated
      in Arabidopsis thaliana. Important new ideas have already emerged from these
      studies such as the importance of the female gametophyte in embryo development,
      and an early silencing of the male genome during the first days following gamete
      fusion.

PMID- 11455879
TI  - Developmental and evolutionary hypotheses for the origin of double fertilization
      and endosperm.
AB  - The discovery of a second fertilization event that initiates endosperm in
      flowering plants, just over a century ago, stimulated intense interest in the
      evolutionary history and homology of endosperm, the genetically biparental embryo
      nourishing tissue that is found only in angiosperms. Two alternative hypotheses
      for the origin of double fertilization and endosperm have been invoked to explain
      the origin of the angiosperm reproductive syndrome from a typical non-flowering
      seed plant reproductive syndrome. Endosperm may have arisen from a developmental
      transformation of a supernumerary embryo derived from a rudimentary second
      fertilization event that first evolved in the ancestors of angiosperms (endosperm
      homologous with an embryo). Conversely, endosperm may represent the developmental
      transformation of the cellular phase of non-flowering seed plant female
      gametophyte ontogeny that was later sexualized by the addition of a second
      fertilization event in a strongly progenetic female gametophyte (endosperm
      homologous with a female gametophyte). For the first time, explicit developmental
      and evolutionary transitions for both of these hypotheses are examined and
      compared. In addition, current data that may be congruent with either of these
      hypotheses are discussed. It is clear that much remains to be accomplished if the
      evolutionary significance of the process of double fertilization and the
      formation of endosperm is to be fully understood.

PMID- 11455880
TI  - Future of early embryogenesis studies in Arabidopsis thaliana.
AB  - Embryogenesis is a long-standing field of interest for plant scientist as
      recorded in the 'notes' of the French Science Academy. This either with
      fundamental or applied points of view. Since the beginning of the century
      techniques and questions have co-evolved, from microscope and fate map to laser
      ablation and cell-cell signalling. So far in plant embryogenesis, a limited use
      has been made of the whole range of approaches generally available to study
      development. This is due to technical limitations when working with plant
      embryos. Novel mutant screens and techniques are now at hand and are expected to
      unravel further the nature of cell interactions underlying embryo development.
      This in turn will modify the focus of our questioning.

PMID- 11455881
TI  - [Lateral cervical tumor of neural etiology: cervical schwannoma].
AB  - Schwannoma are benign tumors of the nerve sheath arising from Schwann cells of
      cranial and spinal nerves. The most frequent sites are the peripheral nerves of
      the head and neck and the flexor surfaces of the upper extremities. Cervical
      schwannoma are rare, which makes them interesting to ENT-specialists. A new case
      of cervical schwannoma is reported, the literature is reviewed and the
      pathogenic, criteria and therapy are discussed.

PMID- 11455882
TI  - [Evaluation methods of the degree of regeneration after experimental nerve
      repair. Evaluation model for the facial nerve in rats].
AB  - The AA. after sever the facial nerve trunk of Wistar mice (so interrupting its
      path owing to the loss of about 4 mm of its anatomical continuity) repair the
      faulty portion with several grafts, and 4 months later consider the gained
      results achieved in each of the following parameters: functional, morphological,
      biochemical and electrophysiological and, finally, compare the own outcomes with
      bibliographic references of literature regarding this subject.

PMID- 11455883
TI  - [Practical considerations of surgical treatment of otosclerosis].
AB  - The ENT-specialist after determine the diagnosis, the deafness degree and the
      requirements of each otosclerotic individual must consider the therapeutic
      possibilities and the end results, also the complications, the indications and
      the contraindications. These considerations are fundamental under the forensic
      medicine viewpoint and a good medical practice and even in order to avoid
      failures provided preestablished prospectives and the outcomes fails to adhere to
      the proposed schedule. Surgical option is promising in cases of severe deafness
      when our aim is to improve the enlargement and recognition of environmental
      sounds when an acoustic prosthesis is not employed. In these cases possibly
      recruitment is present at the initial stages, which requires and adaptation
      period. Also must be analyzed the influence for surgery of environment factors
      and life-style (pressure changes, ambient noise, etc.), the existence of
      tinnitus, equilibrium disorders, hard of hearing features and the age. Results
      procured with surgery in unilateral otosclerosis are lesser compared with
      bilateral, which in association with the fact that in the majority od unilateral
      the degree of impairment (percent of binaural deficit) is minimal, compel us to
      be very cautions in counseling these patients.

PMID- 11455884
TI  - Saccadic eye movement and visual pathways function in diabetic patients.
AB  - We assessed saccadic eye movements (SEM) and the visual evoked potentials (VEP)
      with the aim to evaluate whether a correlation exist between SEM and visual
      pathways function, in insulin-dependent diabetes mellitus (IDDM) patients. In
      IDDM patients we observed significantly longer SEM latency, while SEM velocity
      and accuracy were similar to those of the controls; VEP showed a significant
      delay of the latencies and significant reduction of the amplitudes in IDDM
      patients no relationship between SEM and VEP parameters were found. In conclusion
      SEM latency delay suggest an impairment of the saccadic eye movement system,
      while impaired VEP may be ascribed to a dysfunction of the visual pathways. The
      lack of correlation between VEP impairment and SEM latency delay suggests that in
      our IDDM patients the delay of saccadic latency could be ascribed to a difuse
      neuronal problem exceeding the visual pathways disfunction.

PMID- 11455885
TI  - [Management of epistaxis in Rendu-Osler-Weber disease].
AB  - The Rendu-Osler-Weber disease is an hereditary hemorrhagic dysfunction with muco
      cutaneous telangiectasia of diverse localization, being able to internal organs
      and committing the life in some cases, not alone for the derived systemic
      complications, but for the quantity of the recurrent nosebleed that are the most
      frequent feature and sometimes restrictive that these patients present. We report
      two family groups with multidisciplinary diagnosis, and analyze them most
      important ENT aspects for this syndrome.

PMID- 11455886
TI  - [Idiopathic thrombosis of the internal jugular vein].
AB  - The internal jugular vein thrombosis is an infrequent vascular complication
      associated in the past to severe infections of the head and neck. We report a
      case with unknown etiology and make a review on the subject discussing on
      etiology, clinical features, diagnosis and treatment.

PMID- 11455887
TI  - [Malignant melanoma of the nasal cavity. Retrospective study. The analysis of p53
      and p16INK4 expression].
AB  - Five cases of malignant melanomata of the nasal cavities have been diagnosed and
      studied at ENT--and Anatomopathological Departments, between 1990 and 1997, the
      group ranging from 65 to 90 years, middle age 74.2. Paramount symptoms were
      epistaxis and lack of pain in all patients. Radical surgery was performed only in
      one case, followed by radiotherapy; the remainder were submitted to palliative
      treatment. We have reviewed the literature and also an immunohistochemical
      analysis about p53, p16INK4 and Rb oncogenes with the aim to establish its
      importance in these tumor's type. The whole group have showed high levels of p53
      and MIB-1 and 60 percent a loss of oncogen p16 expression.

PMID- 11455888
TI  - [Early diagnosis of nasopharyngeal carcinoma].
AB  - For making an early diagnosis of nasopharyngeal carcinoma it is fundamental to
      fulfill three requirements. First a high suspicion index based in the knowledge
      of symptoms and signs of the malady. Secondly it is necessary the routinely use
      in the consulting room of a nasopharyngoscope. An in third place is to make, in
      doubtful cases, an enlarged biopsy under endoscopic control and local anesthesia.

PMID- 11455889
TI  - Milk fever and subclinical hypocalcaemia--an evaluation of parameters on
      incidence risk, diagnosis, risk factors and biological effects as input for a
      decision support system for disease control.
AB  - The present review analyses the documentation on incidence, diagnosis, risk
      factors and effects of milk fever and subclinical hypocalcaemia. It is hereby
      evaluated whether the existing documentation seems sufficient for further
      modelling in a decision support system for selection of a control strategy.
      Several studies have been carried out revealing an incidence of milk fever most
      often in the level of 5-10%. Few studies indicate that the incidence of
      subclinical hypocalcaemia is several times higher than milk fever. The diagnosis
      based on clinical or laboratory methods or based on presence of risk factors is
      outlined. The clinical symptoms of milk fever are highly specific and the disease
      level may thus be determined from recording of treatments. Diagnosis of
      subclinical hypocalcaemia needs to include laboratory examinations or it may be
      determined by multiplying the incidence of milk fever by a certain factor. From
      the documentation on risk factors, it is very complex to predict the incidence
      from the exposure level of the risk factors. Due to uncertainty, sensitivity
      analyses over a wide range of values for each parameter are needed. The
      documentation of cow characteristics, nutrition, environment and management as
      risk factors are described. Among cow characteristics, parity or age, body
      condition and production level were found to be important. Risk factors
      associated with nutrition included most importantly dietary cation-anion
      difference and calcium level whereas the importance of general feeding related
      factors like type of feed stuff and feeding level were less clear. Environment
      and management included season, climate, housing, pasturing, exercise, length of
      dry period and prepartum milking. Several of the parameters on environment and
      management were confounded among each other and therefore firm conclusions on the
      importance were difficult. The documentation of the effect of milk fever includes
      the downer cows, reproductive disorders, occurrence of other diseases and the
      effect on milk production, body weight and culling. The reproductive disorders
      included most importantly dystocia, uterine prolapse, retained placenta, metritis
      and repeat breeding, and occurrence of other diseases included ketosis, displaced
      abomasum and mastitis. The documentation was substantial and often quantifiable
      within certain limits. Overall it is concluded that the present documentation on
      milk fever concerning incidence, diagnosis, risk factors and effects seems
      sufficient for a systematic inclusion in a decision support system. A model on
      milk fever should take into consideration the variation in biological data and
      individual herd characteristics. The inclusion of subclinical hypocalcaemia would
      be more uncertain and probably should await further documentation on
      possibilities of determining the herd level incidence and also the effect of this
      condition on production.

PMID- 11455890
TI  - Morphology of the leather defect light flecks and spots.
AB  - The skin histology and the scanning electron microscope morphology of the hide
      defect light flecks and spots after tanning were studied in 11 steers infested
      with biting lice (Damalinia bovis). Nine steers from herds free of lice were used
      as controls. Skin biopsies from 6 of the animals in the lice infested group
      showed mild to moderate hyperkeratosis and moderate perivascular to diffuse
      dermatitis with infiltration of mainly mononuclear cells and some eosinophilic
      granulocytes. The steers were slaughtered at an age of 18 to 23 months. Light
      flecks and spots occurred on all examined hides from the infested group after
      tanning. No examined hides from the control group demonstrated similar damage.
      Both light microscopic examination of sections of tanned hide with light flecks
      and spots and scanning electron microscopy of the same defects showed superficial
      grain loss and craters with a irregular fibre base encircled by smooth and intact
      grain. The association between louse infestation at an early age and damage of
      hides following slaughter 6 to 15 months later, suggested that louse infestations
      lead to a prolonged or lifelong weakening in the dermis. This weakening may cause
      superficial grain loss during the tanning process.

PMID- 11455891
TI  - Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite
      vaccination.
AB  - The present report describes the clinical, pathological, serological and
      virological findings in calves from 2 larger Danish beef herds experiencing
      outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine
      respiratory syncytial virus (BRSV) vaccine 2 months prior to the outbreak. The
      clinical signs comprised nasal discharge, pyrexia, cough and increased
      respiratory rates. A total of 28 calves died in the 2 herds. The laboratory
      investigations revealed that BRSV was involved and probably initiated both
      outbreaks. Furthermore, the serological results suggested that the vaccine
      induced only sparse levels of antibodies probably due to the presence of
      maternally derived antibodies at the time of vaccination. Necropsy findings in 5
      calves revealed changes typical for infectious pneumonia with involvement of
      BRSV. In conclusion, vaccination of calves against BRSV in 2 Danish beef herds
      failed to protect the calves against severe or even fatal BRSV mediated
      respiratory disease 2 months later.

PMID- 11455892
TI  - Cubicle refusal and rearing accommodation as possible mastitis risk factors in
      cubicle-housed dairy heifers.
AB  - Fifty-nine of the 65 dairy farms with cubicle sheds in the Norwegian county of
      Oppland in 1990 were included in a study of rearing accommodation, cubicle
      refusal and mastitis incidence. The farmers recorded the favoured resting
      location of the individual cows and heifers throughout the final week of
      pregnancy as well as during calving. The observations were matched with
      individual records of mastitis cases during the first 30 days after calving.
      Mastitis incidence in the heifers was analysed by logistic regression using
      rearing accommodation and cubicle refusal as independent variables, controlling
      for herd as a clustering factor. Cubicle refusal was found in 29% of the heifers,
      but in only 3% of older cows. The results of the analysis indicated a tendency
      for cubicle refusal to be associated with an increased mastitis incidence among
      the heifers (OR = 2.2, c.i.95%OR = 0.9-5.4, P = 0.08). Cubicle refusal accounted
      for 21% (0-32%) of the mastitis cases in the study population (PAF = 0.21).

PMID- 11455893
TI  - Management of calving in Norwegian cubicle-housed dairy herds.
AB  - Sixty of the 65 dairy farms with cubicle houses in the Norwegian county of
      Oppland were included in a field study of the management of calving in 1990. The
      farmers recorded the location of the cow when giving birth, farmer presence and
      whether assistance was given during calving, occurrence of suckling, and time
      after birth when cow and calf were separated. Such data were recorded for a total
      of 1125 calvings. About 10% occurred on pasture, while 78% of the remaining
      calvings took place in the cubicle-equipped section. Thirteen percent calved in a
      calving pen, the remaining cows being tethered at the time of calving. Thirty-two
      percent of the calvings took place in houses lacking a calving pen altogether.
      Farmers were present during 41% of the calvings. Suckling most frequently
      occurred after pasture calvings, and was least frequent after calvings within the
      cubicle-equipped section of the cowhouse. Injuries to the calf caused by
      trampling or contact with fittings etc. were rare, and no more common in
      association with calving in the cubicle-equipped section than with calving taking
      place with the cow isolated from the rest of the herd. All calves were removed
      from their dams within 24 h after birth.

PMID- 11455894
TI  - Changes in some blood micronutrients, leukocytes and neutrophil expression of
      adhesion molecules in periparturient dairy cows.
AB  - Dairy cows are highly susceptible to infectious diseases, like mastitis, during
      the period around calving. Although factors contributing to increased
      susceptibility to infection have not been fully elucidated, impaired neutrophil
      recruitment to the site of infection and changes in the concentrations of some
      micronutrients related with the function of the immune defence has been
      implicated. Most of the current information is based on studies outside the
      Nordic countries where the conditions for dairy cows are different. Therefore,
      the aim of the study was to evaluate changes in blood concentrations of the
      vitamins A and E, the minerals calcium (Ca), phosphorous (P), and magnesium (Mg),
      the electrolytes potassium (K) and sodium (Na) and the trace elements selenium
      (Se), copper (Cu) and zinc (Zn), as well as changes in total and differential
      white blood cell counts (WBC) and expression of the adhesion molecules CD62L and
      CD18 on blood neutrophils in Swedish dairy cows during the period around calving.
      Blood samples were taken from 10 cows one month before expected calving, at
      calving and one month after calving. The results were mainly in line with reports
      from other countries. The concentrations of vitamins A and E, and of Zn, Ca and P
      decreased significantly at calving, while Se, Cu, and Na increased. Leukocytosis
      was detected at calving, mainly explained by neutrophilia, but also by
      monocytosis. The numbers of lymphocytes tended to decrease at the same time. The
      mean fluorescent intensity (MFI) of CD62L and CD18 molecules on blood neutrophils
      remained constant over time. The proportion of CD62L+ neutrophils decreased
      significantly at calving. The animals were fed according to, or above, their
      requirements. Therefore, changes in blood levels of vitamins, minerals and trace
      elements were mainly in response to colostrum formation, changes in dry matter
      intake, and ruminal metabolism around calving. Decreased levels of vitamins A and
      E, and of Zn at calving might have negative implications for the functions of the
      immune defence. The lower proportion of CD62L+ neutrophils at calving may result
      in less migration of blood neutrophils into the tissues, and might contribute to
      the increased susceptibility to infections at this time.

PMID- 11455895
TI  - 15-ketodihydro-PGF2 alpha, progesterone and cortisol profiles in heifers after
      induction of parturition by injection of dexamethasone.
AB  - In order to study rapid changes in 15-ketodihydro-PGF2 alpha, cortisol and
      progesterone in the period preceding parturition in cattle, pre-term parturition
      was induced in 4 late pregnant heifers. Parturitions were induced by 2
      intramuscular injections of 20 mg dexamethasone with a 24-h interval. The first
      injection was made on days 254, 258, 264 and 265 in gestation, respectively.
      Twenty-four h before the first injection an intravenous polyurethane cannula was
      inserted. Blood samples were collected at least every hour until 12 h after
      parturition and during the second stage of labour at least 6 times per hour.
      Plasma was analysed for 15-ketodihydro-PGF2 alpha and progesterone by
      radioimmunoassays, and for cortisol by an ELISA. The average time from injection
      to parturition was 7.7 (6.6-8.9) days (mean (range)). Two of the heifers had
      retained foetal membranes (RFM). At the start of the experiment the levels of
      PGF2 alpha metabolite were low (< 300 pmol/L) and increased slowly to levels
      between 1000 and 2000 pmol/L at one day before parturition. During the last day,
      however, the levels increased rapidly and the highest levels (> 10,000 pmol/L)
      were reached at the time of delivery. No pulsatile release was seen. Immediately
      after foetal expulsion the PG-metabolite levels decreased rapidly in all animals.
      In the 2 animals with RFM, however, this decline ceased within a few h. The PG
      metabolite levels in these animals then started to increase and reached levels as
      high as during parturition. Luteolysis occurred between 1.6 and 0.4 days before
      parturition in all animals. The cortisol profile showed a distinct peak at the
      time of parturition in the RFM heifers. This peak was absent in the non-RFM
      heifers. This study shows that the PGF2 alpha release at prepartal luteolysis and
      parturition is not pulsatile in cattle and that cortisol profiles in heifers with
      retained foetal membranes might differ from the profiles in non-RFM heifers at
      the time of parturition.

PMID- 11455897
TI  - Failure to use cubicles and concentrate dispenser by heifers after transfer from
      rearing accommodation to milking herd.
AB  - Thirty-three dairy farms in the Norwegian counties of Ostfold and Akershus in
      which cubicle sheds had been in use for at least one year and with a herd size of
      less than 60 cows, were contacted and asked to participate in a study. The study
      focused on heifers' use of cubicles and concentrate dispenser just after being
      transferred from rearing accommodation to the milking herd. For each heifer, the
      farmer recorded cubicle use once nightly between 9 and 11 pm. The daily amount of
      concentrate released in the dispenser and the allotted daily ration were also
      recorded. The recording period was 15 consecutive days for cubicle use and 7 days
      for concentrate dispenser use. Cubicle refusal behaviour, i.e. lying outside the
      cubicles, was analysed by logistic regression using rearing accommodation of
      heifers, herd size, heifer age, and housing layout as independent variables, and
      herd as a clustering variable. On Day 2 after transfer, 34% of the heifers were
      showing cubicle refusal behaviour (N = 340). By Day 15 this percentage had
      dropped to 23. Cubicle refusal was lower throughout the whole period among
      heifers which used the cubicles on the 3 first days after transfer compared to
      those which did not. This tendency could also be detected several months later.
      The analysis showed cubicle refusal to be significantly associated with rearing
      accommodation (OR = 6.1, c.i.95%OR = 1.5-24.3, P = 0.01) and cubicle layout in
      the shed (OR = 0.2, c.i.95%OR = 0.0-0.7, P = 0.01). None of the tested variables
      were found to be significant for failure to use the concentrate dispenser, a
      behaviour which was less frequent than cubicle refusal. However, 8 percent of the
      heifers did not visit the dispenser at all throughout the 7 days of observation.

PMID- 11455896
TI  - Regulation by gonadal steroids of estrogen and progesterone receptors along the
      reproductive tract in female lambs.
AB  - The regulation of estrogen and progesterone receptor (ER, PR) expression by
      estradiol (E2) and progesterone (P4) in the oviduct, uterus and cervix of female
      lambs was studied. The animals received three intramuscular injections of E2, P4
      or vehicle with an interval of 24 h and they were slaugthered 24 h after the
      third injection. Determinations of ER and PR were performed by binding assays and
      mRNAs of ER alpha and PR by solution hybridization. High levels of ER and PR in
      both cervix and oviduct were found in the female lamb, differing from other
      mammalian species. No significant effects by either E2 or P4 treatment on ER and
      PR levels in the cervix and oviduct could be observed. E2 treatment increased the
      mRNA levels of ERa and PR more than 3-fold in the cervix, while P4 treatment
      increased the mRNA levels of ERa and PR in the uterus. The results show
      differential effects of gonadal steroids on sex steroid receptor expression along
      the reproductive tract in female lambs, suggesting that steroid target tissues
      can modulate responses to the same circulating levels of steroid hormones.

PMID- 11455898
TI  - Cubicle refusal in Norwegian dairy herds.
AB  - In order to survey the behaviour of choosing the alley area instead of a cubicle
      as a lying place (cubicle refusal), a questionnaire was sent to the 273 dairy
      farms in Norway known to keep cows in cubicle housing systems. Sixty-six percent
      of the farmers contacted were included in the study. The median herd size was 18
      cows (range 7-118). More than 85% of the herds had sheds providing one or more
      cubicles per cow. The mean herd occurrence of cubicle refusal was 6%, but showed
      great variation (range 0-55%). Regression analysis showed a significant
      association between rearing heifers in slatted floor pens and an increased
      cubicle refusal occurrence (p = 0.02, R2 = 0.05), while herd size, use of litter,
      or cubicle-to-animal ratio were not found to be associated with cubicle refusal.
      The practice of rearing heifers in slatted floor pens accounted for about one
      half of the observed cubicle refusal (etiologic fraction = 0.51).

PMID- 11455899
TI  - Antibacterial drugs prescribed for dogs and cats in Sweden and Norway 1990-1998.
AB  - The usage of veterinary antibacterial drugs in dogs and cats in Sweden and Norway
      for the period 1990-1998 was investigated by use of drug wholesalers' statistics.
      Additionally, usage of human antibacterial drugs in these species in Sweden was
      investigated by use of prescription data for the period 1996-1998. On average,
      more than 50% of the prescribed veterinary antibacterials in Sweden were beta
      lactam antibiotics. In Norway, about 75% of the preparations prescribed for dogs
      and cats contained sulfonamides and trimethoprim. Furthermore, the prescription
      data from Sweden showed a reduced usage of human antibacterials prescribed for
      dogs and cats since the beginning of the 1980s. Approximately 20% of the
      prescribed packages for dogs in the years 1996-1998 were human approved drugs.
      The corresponding figure for cats was 13%. The differences between the countries
      in the choice of antibacterial drugs can be explained by differences in the
      availability of approved preparations during the study period. The consumption of
      veterinary antibacterials in dogs and cats in Sweden during the period was in the
      range of 3% to 8% of the total use of veterinary antibacterials. The
      corresponding figures in Norway were in the range of 3% to 7%. It is of vital
      importance to study usage patterns of antibacterial drugs in dogs and cats in
      surveillance and control of bacterial resistance, but also in discussions of
      therapeutic appropriateness. Therefore, further research is needed in this area.

PMID- 11455900
TI  - Plants as de-worming agents of livestock in the Nordic countries: historical
      perspective, popular beliefs and prospects for the future.
AB  - Preparations derived from plants were the original therapeutic interventions used
      by man to control diseases (including parasites), both within humans and
      livestock. Development of herbal products depended upon local botanical flora
      with the result that different remedies tended to develop in different parts of
      the world. Nevertheless, in some instances, the same or related plants were used
      over wide geographic regions, which also was the result of communication and/or
      the importation of plant material of high repute. Thus, the Nordic countries have
      an ancient, rich and diverse history of plant derived anthelmintic medications
      for human and animal use. Although some of the more commonly used herbal de
      wormers were derived from imported plants, or their products, many are from
      endemic plants or those that thrive in the Scandinavian environment. With the
      advent of the modern chemotherapeutic era, and the discovery, development and
      marketing of a seemingly unlimited variety of highly efficacious, safe synthetic
      chemicals with very wide spectra of activities, herbal remedies virtually
      disappeared from the consciousness--at least in the Western world. This attitude
      is now rapidly changing. There is a widespread resurgence in natural product
      medication, driven by major threats posed by multi-resistant pest, or disease,
      organisms and the diminishing public perceptions that synthetic chemicals are the
      panacea to health and disease control. This review attempts to provide a
      comprehensive account of the depth of historical Nordic information available on
      herbal de-wormers, with emphasis on livestock and to provide some insights on
      potentially rewarding areas of "re-discovery" and scientific evaluation in this
      field.

PMID- 11455901
TI  - Impact of postovulatory food deprivation on the ova transport, hormonal profiles
      and metabolic changes in sows.
AB  - The effect of food deprivation on ova transport, hormonal profiles and metabolic
      changes was studied in 20 crossbred multiparous sows during their second oestrus
      after weaning. To determine the time of ovulation, transrectal ultrasonographic
      examination was performed. The sows were divided into 2 groups, one control group
      (C-group), which was fed according to Swedish standards, and one experimental
      group (E-group). The E-group sows were deprived of food from the first morning
      meal after ovulation until slaughter. Blood samples were collected every second
      hour from about 12 h before expected ovulation in the second oestrus after
      weaning until slaughter and were analysed for progesterone, prostaglandin F2
      alpha-metabolite, insulin, glucose, free fatty acids and triglycerides. All sows
      were slaughtered approximately 48 h after ovulation and the genital tract was
      recovered. The isthmic part of the oviduct was divided into 3 equally long
      segments and flushed separately with phosphate buffered saline (PBS). Uterine
      horns were also flushed with PBS. A significantly greater number of ova were
      found in the first and second part of the isthmus in the E-group (p = 0.05) while
      in the C-group most of the ova were found in the third part of the isthmus or the
      uterus (p = 0.01). The level of prostaglandin F2 alpha-metabolite was
      significantly higher in the E-group compared with the C-group. The concentration
      of progesterone increased in both groups after ovulation but there were no
      significant differences between the groups. The other blood parameters showed
      that the food-deprived sows were in a catabolic state. The 48 h period of fasting
      results, directly or indirectly in an delayed ova transport, which may be due to
      a delayed relaxation in the smooth circular muscle layer of the isthmus.

PMID- 11455902
TI  - Comparison of worm control strategies in grazing sheep in Denmark.
AB  - Control of nematode parasites with reduced reliance on the use of anthelmintics
      was studied in 16 ewes with suckling twin lambs on contaminated pasture in
      Denmark. Ewes and lambs were treated with albendazole at turn-out 3 May. Ewes
      were removed from the groups on 26 July, and lambs were slaughtered on 11
      October. The animals were allocated to 4 groups of 8 lambs and their 4 ewes.
      Group TS was treated with albendazole at weeks 3, 6 and 8 after turnout and set
      stocked; group TM was similarly treated but moved to clean pasture in conjunction
      with the last drenching; group US was untreated and set-stocked, and group UM was
      left untreated but moved to clean pasture week 8 after turn-out. Supplementary
      feed was offered in June and August due to scarcity of pasture. Strategic
      treatments of ewes and lambs weeks 3, 6 and 8 after turn-out, with or without a
      move to clean pasture, were highly effective in controlling nematode infections
      for most of the season. This was reflected in better weight gains and carcass
      characteristics in the treated compared to untreated lambs, resulting in an
      average increase in the value of the product by 36%. The effect of moving without
      treatment (UM) on faecal egg counts was limited but peak pasture infectivity was
      reduced to less than 10% compared to the set-stocked group and weight gains of
      lambs were significantly better despite poor feed availability in late season.
      The study showed that under set-stocked conditions repeated anthelmintic
      treatments of both ewes and lambs in early season may ensure sufficient nematode
      control whereas moving animals to clean pasture without dosing was less
      efficient. The latter may, however, still be a viable option in organic and other
      production systems where routine use of anthelmintics is banned, particularly if
      weaning and moving are combined or a second move is performed.

PMID- 11455903
TI  - Demographic data of a population of insured Swedish dogs measured in a
      questionnaire study.
AB  - Dogs, in the age range 1-3 years old, were randomly selected from the largest
      animal insurance database in Sweden for inclusion in the study. The study was
      performed in 1997, and a total of 680 dog owners were selected for the study. A
      total of 461 dog owners completed the survey, at an overall response rate of 68%.
      Data was compared to a recent gallup performed on a sample of all dogs in Sweden.
      The demographic statistics of the insured dog population were in many aspects
      similar to the total dog population of Sweden. Typical for both insured dogs and
      the total population of dogs were a low proportion of neutered dogs, that many
      dogs were bought at an early age, that many dogs were in contact with a "breeder"
      when sold, and a similar profile of health status. However, "dog breeders" seemed
      to have their dogs insured to a higher extent than the general dog owner. It was
      concluded that as the populations were alike in many respects, it is reasonable
      to use the insurance database for epidemiological studies on diet and exercise in
      Swedish dogs.

PMID- 11455904
TI  - Eradication of lice in cattle.
AB  - The purpose of this field study was to develop and evaluate eradication as a
      strategy to control lice in cattle. Thirty-three herds of cattle were selected
      and observed during a period of two and a half years. Before eradication, biting
      lice (Damalinia bovis) were present in 94% of the herds and 27% of the animals.
      Sucking lice (Linognathus vituli) were present in 42% of the herds and 5% of the
      animals. These levels were very similar to those reported from other countries in
      Northern Europe. The eradication strategy was successful in 28 of 33 herds, but
      lice were still present in 5 herds 3 to 6 months after treatment. Biting lice
      were present in all these 5 herds, sucking lice were present in 3 herds. During
      the next 12 months, nine of the 28 herds were reinfected with lice. Six herds
      were reinfected with just biting lice, 2 herds with just sucking lice and one
      herd was reinfected with both. There was no significant difference between the 2
      louse species regarding the risk of unsuccessful eradication or reinfection. The
      only significant risk factor for reinfection was either purchase of livestock or
      use of common pasture, combined with failure in pre-treatment of newly introduced
      animals.

PMID- 11455905
TI  - Variation in the level of grain defect light flecks and spots on cattle hides.
AB  - The occurrence of hide damage light flecks and spots was determined on tanned
      hides from 28 herds during a period of 8 to 12 months. Light flecks and spots are
      described as small areas of grain loss up to 3 mm in diameter that are seen on
      dyed crust cattle leather. Damage was found on 75.8% of all hides. The neck and
      shoulders were the anatomical region with the highest prevalence of damage. Sixty
      eight per cent of all hides had light flecks and spots in this region. The
      forelimbs and dewlap were the anatomical region with the second highest
      occurrence with a prevalence of 39.1%. This distribution corresponded to the
      known distribution of lice in cattle. No significant differences were observed in
      age, sex, prevalence of lice in the herd assessed in March or infestations with
      different lice species. The frequency of light flecks and spots varied
      significantly during the year. The frequency was highest in the late winter and
      early spring, decreased significantly during the summer and was lowest in the
      autumn. This variation supported the importance of lice in the development of
      light flecks and spots and suggested a relatively long healing period for the
      damages induced by lice.

PMID- 11455906
TI  - The effect of eradication of lice on the occurrence of the grain defect light
      flecks and spots on cattle hides.
AB  - The influence of an eradication programme for lice on the prevalence of light
      flecks and spots on cattle hides was studied in 33 dairy cattle herds during a
      period of two and a half years. Lice were eradicated from the main group of herds
      after 9 to 12 months and the quality of the hides before and after treatment was
      compared. Hides from slaughtered animals were collected during the study period,
      tanned and examined with special emphasis on the occurrence of the grain damage
      light flecks and spots. The prevalence of hides without light flecks and spots
      increased from 24.2% before treatment to 61.6% after treatment. The prevalence of
      hides free from the damage increased significantly in all examined anatomical
      regions. The improvement in hide quality was most marked in the shoulders and
      neck region which corresponded to the major predilection site of cattle lice. The
      prevalence of hides with light flecks and spots started to decrease in the first
      period (2-40 days) after eradication. The changes after treatment suggested that
      most healing process took place over a period of about 4 months. The eradication
      programme eliminated the seasonal variation in the prevalence of light flecks and
      spots which was present before treatment.

PMID- 11455907
TI  - [The release of forensic patients (63 StGB) and the problem of predicting
      dangerousness].
AB  - This article presents first results of a prospective prediction study with
      participation of twenty-three forensic institutions from seven states of FRG.
      Main objective of this study is the determination of valid criteria for
      predicting recidivism of mentally disordered offenders. This evaluation (n = 188)
      investigates which patients are presently released from forensic institutions. In
      comparison to previous studies the releases per annum have decreased
      significantly. In the last two years there has been an increase in release of
      schizophrenic patients and a decrease in release of patients with a personality
      disorder and sexual offenders. In addition it has been analyzed which criteria
      therapists use to predict dangerousness from a clinical point of view.

PMID- 11455908
TI  - [The importance of the type concept in psychiatry].
AB  - The significance of the typological approach in psychiatry, which has been partly
      forgotten and partly considered to be outdated at present, is discussed. It
      follows from considerations of terminology and the critique of knowledge that on
      the basis of its taxonomic function logically and unambiguously determined by
      Hempel and in particular by Oppenheim, type, in contrast to class, is capable of
      categorizing majorities with blurred dividing lines. It was in this function that
      the concept of type entered psychology through W. Stern as a means of
      systematically categorizing the multiplicity of psychological varieties in
      different groups of persons, whereby the polar definition of the type concept as
      developed by Krueger and Wellek in genetic holistic psychology proved to be
      taxonomically effective. Type gained significance in psychiatry as polarity, in
      particular in the framework of research into constitution and psychopathy. Anglo
      Saxon criticism of the concept of type and the evident differences between
      American DSM psychiatry and the German concept of type are examined. The current
      methods of typological research in psychiatry have been developed in the
      preceding thirty years mainly by Zerssen and his team using modern uni- and
      multivariate statistical methods and successfully applying them. As a result, it
      was possible to objectify in several studies in the meantime Tellenbach's typus
      melancholicus, the typus manicus (v. Zerssen), as well as the typus migraenicus
      (Peters) as premorbid personality types. In addition, a circular typology of
      personality variants is beginning to emerge ever more clearly in the latest
      studies on the basis of which it may be possible to identify individual
      personality disorders typologically.

PMID- 11455909
TI  - [Social rank and depression--an example of "evolutionary psychopathology"].
AB  - Affective disorders are pathological alterations of phylogenetically old
      emotional mechanisms the adaptive function of which is still a matter of debate.
      According to the social competition hypothesis, depressive syndromes involve
      activation of a mechanism serving subordination in competitive situations. This
      mechanism protects the individual from the damaging consequences of an escalating
      agonistic encounter. The paper critically discusses supporting evidence culled
      from biological, clinical and psychological findings. Animal models show
      phenomenological similarities between subordination and depression. In primates
      affiliative behavior and social bonding are closely linked to rank-related
      behaviors. Common biochemical and pharmacological features of subordination and
      depression include an activation of the stress axis, diminished serotonergic
      neurotransmission and modification by antidepressants. However, the
      discrimination between a specific subordination reaction and an unspecific stress
      response is often controversial. Many clinical and psychological aspects of
      depressive syndromes may be understood as an--exaggerated--submissive behavior,
      but have rarely been studied in that light. Typical endogenous depression and
      bipolar disorders challenge the social competition hypothesis. While the manic
      syndrome, due to its similarity to dominance behavior, supports the link between
      social competition and affective disorders, the cyclic alteration of mood cannot
      be sufficiently explained by the social competition hypothesis alone.

PMID- 11455910
TI  - [Clomethiazole as an adjuvant in the treatment of confusional psychosis].
AB  - We report on the successful treatment of two female patients with the clinical
      features of severe confusional psychosis. The clinical picture of these cases was
      characterized by lability of mood, disorientation, delusions, hallucinations,
      misidentification of persons, severe thought disorder and impaired memory. A 55
      year old female inpatient suffered from a psychotic episode with the clinical
      features of confusional psychosis. Medical history showed three proceeding
      confusional psychotic episodes. In the second case a 32-year old female inpatient
      suffered from a severe postpartum psychosis with the clinical features of
      confusional psychosis. In this case there was no clinical history of psychotic
      episodes. After nonresponsive treatment with neuroleptics and mood-stabilizers,
      both responded rapidly to additional medication with clomethiazole within a week,
      exhibiting a marked reduction in clinical signs and symptoms. A brief review
      about this delirium-like psychosis and current knowledge of therapeutic
      strategies is presented. We discuss clomethiazole as a possible potential adjunct
      in the treatment of confusional psychoses.

PMID- 11455911
TI  - [Testing and validation of the German version of the Stroke Impact Scale].
AB  - Suitable and psychometrically tested instruments to assess health-related quality
      of life in stroke patients are still lacking in German speaking countries. The
      current paper describes the translation and psychometric testing of the German
      version of the Stroke Impact Scale, which was developed as a self- and proxy-
      report measure in the United States to assess the consequences of a stroke. The
      instrument contains 64 Likert-scaled items and assesses eight dimensions of
      health-related quality of life ("strength", "memory and thinking", "emotion",
      "communication", "ADL/IADL", "mobility", "hand function", and "participation").
      The questionnaire was used in a cross-sectional study of 137 persons with stroke
      and was psychometrically tested. The results of this psychometric testing show a
      good acceptance on part of the interviewees. Convergent validity of the SIS
      dimensions was assessed with correlation of the SIS subscales and subscales of
      the short form SF-36 and Nottingham Health Profile and criteria-related validity
      was examined by comparison of mean scores across groups defined by Rankin scores.
      The reliability of the questionnaire was determined through internal consistency
      (Cronbach's). The German version of the SIS is a reliable and valid instrument to
      assess health-related quality of life, but more studies are needed to make
      statements about sensitivity of the instrument, psychometric quality of the proxy
      version and suitability of the questionnaire for specific stroke subgroups.

PMID- 11455912
TI  - [Morphology of the hypoplastic left heart syndrome from the surgical
      perspective].
AB  - Hypoplastic left heart syndrome (HLHS) is found in a wide spectrum of changes of
      the mitral valve, left ventricle and aorta. It represents a critical congenital
      heart disease with a small left ventricle and stenosis or atresia of the aortic
      and the mitral valve. The knowledge of a detailed anatomy of this lesion is
      necessary from the viewpoint of assessment of all possibilities of the surgical
      treatment, interventional cardiological procedures or foetal cardiac surgery.
      Sixty one hearts with HLHS from the collection of heart specimens with congenital
      heart malformations were reviewed. The existence of a wide spectrum of
      malformations of all heart structures was proved. In all the cases enlarged right
      atrium and right ventricle was found. In 23.0% of specimens foramen ovale was
      restrictive or closed. The left ventricle was small in all the hearts, extreme
      hypoplasia was observed in 26.2% in presence of a combination of the mitral and
      the aortic atresia. Most commonly, the combination of mitral stenosis with aortic
      atresia (36.1%) and combination of mitral and aortic stenosis (32.8%) were
      present. Mitral atresia with aortic stenosis was identified in 4.9% cases. The
      mitral valve was usually dysplastic with short and thick chordae and smaller
      annulus. In 39.3% of all hearts fibroelastosis of the left ventricular
      endocardium was present. In these cases moderate degree hypoplasia of the left
      ventricle in combination with mitral and aortic stenosis was often found (65.0%).
      All the aorta was hypoplastic starting from the aortic valve, across the
      ascendent part and aortic arch until the isthmus. Its diameter usually varied
      between 2 and 4 mm. Coarctation of the aorta was found in 16.4% hearts.
      Persistent left superior caval vein represented the most common associated heart
      lesion. From the surgical point of view, nearly in all reviewed hearts Norwood
      surgery, consisting in aortic reconstruction from aorta, main pulmonary artery
      and a patch from the pulmonary homograft could be performed. Reconstruction would
      be very difficult in presence of an extreme hypoplasia of the ascending aorta.
      Until present, possibilities to prevent the development of the left ventricular
      hypoplasia by a foetal surgical intervention or possibility of the surgical
      augmentation of the left ventricle by excision of a thick endocardium do not
      cross the horizons of theory.

PMID- 11455913
TI  - [Oncocytoma of the kidney--morphologic variation in 102 cases].
AB  - From the collection of 2500 cases of renal epithelial tumors in our files, 102
      renal oncocytomas were analyzed for size, multifocality and a morphologic
      spectrum of the growth pattern. The size of the tumors ranged from 1.5 to 13 cm
      in diameter, with a mean of 6.3 cm. Three cases were multifocal, four cases were
      combined with another primary renal tumor (1x angiomyolipoma, 1x conventional
      renal carcinoma, 2x papillary renal cell carcinoma). A central fibrosis or a scar
      was noted in 13 cases, and there was a gross area of hemorrhage in 11 cases. In 4
      cases extensive necroses were recognized. Histologically, an alveolar pattern was
      noted in 70 cases. A tubular pattern was revealed in 31 cases and an unusual
      tubopapillar ("glomeruloid") pattern was noted in one case. Foci of atypical
      nuclei were identified in 58 cases. In 4 oncocytomas broad areas of clearance of
      the oncocytes were found. Psammoma bodies were recognized in 9 tumors and foci of
      ossification were present in 4 cases. Intracellular and extracellular hyaline
      globules were noted in two cases. Renal oncocytoma has a variable morphologic
      spectrum, and its diagnosis should be based on an analysis of structural and
      cytologic features. Differential diagnosis of renal oncocytomas with various
      tumors of the kidney which contain granular cytoplasm is discussed. These tumors
      with granular cytoplasm include conventional renal cell carcinomas, chromophobe
      cell carcinomas, and rare examples of papillary renal carcinomas.

PMID- 11455914
TI  - [Morphometric parameters of nuclei in EBV-positive and EBV-negative Hodgkin's
      lymphoma].
AB  - Five morphometric parameters of nuclei of EBV-positive and EBV-negative Hodgkin's
      lymphoma cells were assessed for length, width, area, circumference, and
      circularity. For the measurement of the nuclei of the tumor cells (Hodgkin, Reed
      Sternberg cells) the system of image analysis "Lucie" was used. In comparison
      with EBV-positive Reed-Sternberg cells, the nuclei of the EBV-negative Reed
      Sternberg cells had significantly larger circumference, area and width. The
      nuclei of the Hodgkin cells in EBV-negative Hodgkin's lymphomas had significantly
      larger width and circularity. The authors assume that the altered morphometric
      parameters are related to a latent EBV infection.

PMID- 11455915
TI  - [Hemorrhagic necrosis of the esophagus].
AB  - A series of 25 necropsy patients aged 54-95 y. with hemorrhagic necrosis of the
      esophagus presented by black mucosa were studied. The discoloration was diffuse
      in most cases; less frequently there were black longitudinal streaks
      corresponding with mucosal folds. In 16 cases, the lesion affected the entire
      esophagus, in the remaining cases only the distal half to third of esophagus was
      affected. The changes ended abruptly at the cardia. Histologically, there was
      necrosis of the mucosa with focal involvement of muscularis mucosae. The necrotic
      tissue was usual densely infiltrated by leucocytes. The submucosa showed edema,
      fibrinorrhagy and slight hemorrhage. There were platelet thrombi in small mucosal
      and submucosal vessels. In only some cases, the infiltrate affected the entire
      muscularis propria. Gastrointestinal bleeding was noted in 8 cases. The
      esophageal lesion was preceded by circulation disorders, as shown in both the
      clinical course and in the autopsy findings. Local hypoperfusion, venous reflux,
      and gastroesophageal reflux appear as the principal pathogenetic factors.

PMID- 11455916
TI  - Benign ectopic prostatic glands in subvesical skeletal muscle. A lesion
      resembling carcinoma.
AB  - In physiological instances, the prostatic acini may be intermingled with striated
      muscle fibers in the apex and in the anterolateral subcapsular areas of the
      prostate. We report an unusual lesion composed of benign prostatic glands, which
      were scattered between skeletal muscle fibers beneath the bladder submucosa. A 55
      year-old man underwent four transurethral resections and radiation therapy for a
      urothelial carcinoma of the urinary bladder. Subsequently a cystectomy was
      performed. In the resection specimen, the prostate specific antigen-positive
      glands were found among the skeletal muscle bundles close to the bladder
      submucosa. They were seen as small groups of haphazardly scattered or isolated
      glands mimicking an infiltrative pattern of a prostatic adenocarcinoma. Prominent
      nucleoli in some glands further contributed to the worrisome appearance of the
      lesion. However, the high molecular weight cytokeratin 34 beta E12 exhibited
      basal cell layers of the glands, and the subsequent course of disease confirmed
      the benign nature of the lesion. The juxtaposition of the prostatic acini with
      the skeletal muscle out of the apex and the anterolateral subcapsular areas of
      the prostate should be included in the differential diagnosis of prostatic
      carcinoma in urinary bladder and prostate biopsies.

PMID- 11455917
TI  - [Congenital myopathy with type 2 fiber hypoplasia].
AB  - An atypical case of congenital myopathy characterised by a low frequency of
      hypoplastic type 2A fibres, type 2B fibre deficiency and type 1 fibre
      predominance is reported. Our patients are siblings, a 10 year old girl and a 7
      year old boy. Both children suffered from ophthalmoplegia and muscle weakness,
      and the boy also showed signs of psychomotoric retardation. A muscle biopsy from
      musculus trapezius has shown type 1 fibre predominance and hypoplastic type 2
      fibres.

PMID- 11455918
TI  - [Inflammatory fibroid polyps of the stomach (case report)].
AB  - Three cases of inflammatory fibroid polyps of the stomach are presented.
      Immunoreactivity for vimentin, actin, and for hystiocytic markers confirmed the
      myofibroblastic and hystiocytic origin of the lesions, as research has shown.

PMID- 11455919
TI  - [80 years since the founding of the autopsy facility at the Kosice State
      Hospital].

PMID- 11455920
TI  - [Effect of terginan on treatment of patients with inflammatory processes in the
      cervix uteri].
AB  - Expediency was studied of use of the drug terginan in a combined treatment of
      uterine neck pathologies in patients presenting with local inflammatory
      processes. The drug was found to be capable of dispelling an unspecific
      inflammatory process, normalizing the vaginal microbe landscape, promoting the
      postcryodestruction epithelization processes as evidenced by the analysis of the
      results obtained.

PMID- 11455921
TI  - [Immunomodulin efficacy in treatment of celiac disease in children].
AB  - Overall forty patients with celiac disease who ranged from 1 to 10 years old were
      kept under medical observation. Measured in the above patient population were the
      following parameters for cellular immunity: the content of T-, B- lymphocytes and
      of subpopulation of T-lymphocytes. In all patients, the content of T- and B
      lymphocytes was reduced. 18 children received immunomodulin as a corrective
      measure in injections and a supporting dose in tablets over two months. There was
      an improvement in clinical symptomatology of the condition that was particularly
      apparent in the long-term results in the presence of increased values for T
      lymphocytes in the group of patients having received immunomodulin against the
      background of basic therapy.

PMID- 11455922
TI  - [Epidemiologic characteristics of bronchopulmanory diseases in workers in the
      porcelain industry].
AB  - Morbidity patterns were studied in those working at the porcelain works, exposed
      to radiant heat, carbon monoxide, silicate dust, noise, xilol, toluene, plumbum.
      Diseases of the respiratory system, particularly acute respiratory viral
      infections (ARVI) were found to prevail in the worker's general morbidity. There
      is an increased respiratory case rate among those individuals working with
      organic solvents, with the incidence rate being related to the service duration.
      The incidence of ARVI, influenza comes to be at its greatest in workers with the
      10-year length of service whereas pneumonia morbidity is most common in those
      workers whose service duration is more then 10 years.

PMID- 11455923
TI  - [Blood plasma level of endothelin in miners of a deep coal mine].
AB  - In 60 miners working in a deep coal mine the blood plasma level of endoteline-1
      (E-1) was measured by the immunoenzyme technique immediately after working shift.
      Those in the mining where the working conditions are especially harsh were found
      to have the highest level of E-1 exceeding the control values. In studying the
      age-related content of E-1 in blood plasma of coal miners the highest levels of E
      1 were recordable in workers 20 to 30 years old, declining and differing in age
      groups 20-30 and 41-50 years old. The level of E-1 was at its greatest in those
      workers with minimum length of service in the underground conditions, declining
      with the service more than 10 years in duration.

PMID- 11455924
TI  - [Medical, social, economic, and legal grounds for compulsory medical insurance in
      Ukraine].
AB  - The article focuses on problems of bringing social compulsory medical insurance
      under regulation, reflected by the Bill, directed towards improvement of medical
      care provision for the population of Ukraine.

PMID- 11455925
TI  - [Logical and mathematic substantiation of selection of a model for health care
      system in a big city].
AB  - Based on the study and analysis of results of the health system activities it can
      be ascertained that the existing system of care of public health is not in a
      position to accomplish tasks it faces related to maintenance and promotion of
      health of the population. A logical-and-mathematical substantiation of an
      essentially new variant of the public health system is submitted. The results of
      the study made formed a basis for carrying a reform of the health system in the
      city of Chernigov.

PMID- 11455926
TI  - [Optimum ways of distribution of medical information among individuals with
      sexually transmitted infections].
AB  - The article is dedicated to the study of most rational ways of dissaminating
      medical information among persons suffering from those infections caught by
      sexual intercourse or genital contact. Optimum canals are determined of influence
      upon different age groups running a risk for this kind of pathology. The most
      optimum way of dissaminating information is television, newspapers, periodicals,
      mail.

PMID- 11455927
TI  - [Screening for kidney diseases in children].
AB  - Screening tests have come to be useful in present-day pediatrics. Implementation
      of the screening is aimed at improving the health status of populations, finding
      it out by death rates as well as by physical and emotional state of those
      patients having been early diagnosed. Overall 846 children with different
      urogenital disorders from children's institutions in the Starokievsky and
      Moskovsky districts of Kiev were examined with the aid of the above screening
      modality. The results obtained confirm the possibility of our diagnosing
      urogenitary disorders on the basis of presence of the whole complex of those
      signs that had been identified for carrying out a screening.

PMID- 11455928
TI  - [Role of E. O. Mukhin in establishing N. I. Pirogov as a physician and a
      scientist].
AB  - The article is dedicated to Ephrem Osipovich Mukhin (1766-1850), a native of
      Ukraine, professor of the Moscow University. The decisive role he had played in
      the moulding of N. I. Pirogov as a physician and scientist is revealed.

PMID- 11455929
TI  - [Changes in various neurophysiological indices in treatment of lumbosacral
      osteochondrosis by combined osteoperiostal electroacupuncture and laser
      puncture].
AB  - The conducted dynamic rheovasographic investigations in 67 patients with
      neurological manifestations of lumbosacral osteochondrosis as well as
      determination of skin temperature in 162 patients, and employment of stimulation
      electromyography in 40 patients showed the presence of definite positive shifts
      (P < 0.001) both in patients with lumboischialgia and in those with the radicular
      pain syndrome, which fact was evidenced by the clinical data suggesting to us the
      feasibility of use of osteoperiostal electropuncture combined with laseropuncture
      with infrared radiation.

PMID- 11455930
TI  - [Peloid application to the area of the adrenal glands projection in the
      rehabilitation therapy of patient with viral hepatitis A and B].
AB  - Submitted in the paper are data secured in investigations designed to study
      efficacies of peloid applications to the area of projection of the adrenal glands
      in patients with the history of viral hepatits A and B presenting with a high
      risk of chronization of the illness. The analysis of the therapy effect was
      performed on the basis of examination of 45 VH reconvalescents with making use of
      clinical, biochemical and immunological investigational techniques. The findings
      obtained suggest restoration during the above therapy of the functional state of
      the liver as well as immunomodulating effect of the method, moderation of
      autoimmunoaggression, and expediancy of its employment in the rehabilitative
      period of VH in those patients presenting with signs of disfunction of the
      immunity system, history of allergoses and presence of concomitant pathology.

PMID- 11455931
TI  - [Clinical and experimental study of spirulina efficacy in chronic diffuse liver
      diseases].
AB  - The results of examination of 60 patients presenting with chronic diffuse
      disorders of the liver and seventy experimental animals with toxic affection of
      the liver, having been administered spirulina treatments, suggest clinical-and
      laboratory effectiveness of this drug. The hepatoprotective properties of
      spirulina are referrable to its antiinflammatory, antioxidant, membrane
      stabilizing, and immunocorrecting actions. In this way the employment of
      spirulina is believed to be pathogenetically validated in chronic diffuse liver
      conditions, permitting stabilizing the process and preventing the transformation
      of chronic hepatitis into hepatocirrhosis.

PMID- 11455932
TI  - [Phytopreparation Diabetin in treatment of patients with insulin-independent
      diabetes mellitus].
AB  - The phytopreparation "Diabetin" has a sugar-reducing, anorexigenic effects,
      facilitates loss of flesh lowering the body mass, causes the manifestations of
      diabetic angio- and neuropathies to delay. It is recommended as treatment of a
      mild form of diabetes as monotherapy or in moderately severe course of the
      trouble it can be used in combination with other peroral sugar-lowering drug
      preparations.

PMID- 11455933
TI  - [Hepatoprotective effect of the sea buckthorn-and-pinks oil].
AB  - Our objective in this study was to reveal hepatoprotective properties of the sea
      buckthorn and sea-buckthorn-pink oils in the experiment in shinshilla rats
      exposed to tetrachloromethane. To assess the progression of hepatitis and
      recovery processes in hepatic cells we used the organ-specific enzyme
      sorbitoldegydrogenase (SDG). The results obtained showed that the sea-buckthorn
      and sea-buckthorn-pink oils promoted normalization of SDG level 5 and 8 days
      respectively earlier than in the control group, which fact is indicative of their
      apparent hepatoprotective properties.

PMID- 11455934
TI  - [Drug design in the 21st century (discussion)].

PMID- 11455935
TI  - Circulating neutrophil priming and systemic inflammation in limb ischaemia
      reperfusion injury.
AB  - BACKGROUND: Recruitment and activation of neutrophils is a key step in the
      development of local and systemic injury in lower limb ischaemia-reperfusion. We
      hypothesis that increased circulating neutrophil priming is responsible for
      systemic inflammation. METHODS: Anaesthetised ventilated swine (n = 6 per group)
      underwent mid-line laparotomy and were randomised to control group or bilateral
      external iliac artery occlusion for two hours followed by two and a half hours
      reperfusion (I/R group). Using luminol, respiratory burst activity was assayed
      with a BioOrbit Luminometer to detect whole blood chemiluminescence (CL) by
      stimulation with phorbol 1,2-myristate 1,3-acetate (PMA) in the absence or
      presence of tumour necrosis factor (TNF) respectively. PMN priming is expressed
      as the ratio of whole blood CL in the presence of TNF to that without. We
      measured plasma interleukin(IL)-6 and tumour necrosis factor alpha by bioassay as
      a measure of systemic inflammation. The alveolar-arterial (A-a) gradient was
      measured using the formula [(A-a)gradient = fraction inspired O2 x 710-(arterial
      pCO2/0.8)-arterial pO2], it is a measure of lung function, a large gradient being
      indicative of impaired oxygen transport and hence lung injury. RESULTS: Lower
      limb I/R caused significantly greater PMN priming, 0.83 +/- 0.14, compared to
      control group, 0.22 +/- 0.04, (p < 0.001). Plasma IL-6, a reliable indicator of
      systemic inflammation, was significantly increased in I/R group after two and a
      half hours of reperfusion, 1295.0 (833.9-2073.0) pg/L, compared to control, 382.9
      (367.4-568.3) pg/L, (p < 0.005). Plasma tumour necrosis factor alpha was
      significantly elevated after one hour of reperfusion in the I/R group, 86.8 (48.7
      106.6) pg/ml, compared to the control group, 32.7 (0.9-42.8) pg/ml, (p < 0.01).
      (A-a) gradient was significantly increased after IRI, 407.97 +/- 53.13, compared
      to the control, 183.19 +/- 45.75, (p < 0.005). Mean pulmonary artery pressure was
      significantly greater after IRI, 38.80 +/- 4.87 mmHg, compared to control, 27.86
      +/- 1.92 mmHg, (p < 0.005). Data represents mean +/- standard error mean or
      median (interquartile range), statistical comparisons using one-way Anova with
      Student's "t"-test and Kruskall-Wallis Anova with the Mann-Whitney U test.
      CONCLUSIONS: Priming of neutrophils increases their circulating respiratory burst
      activity and ability to induce tissue injury. Systemic PMN priming during hind
      limb ischaemia-reperfusion injury is associated with the systemic inflammatory
      response syndrome.

PMID- 11455936
TI  - Reviewers' role in improving manuscripts.

PMID- 11455937
TI  - [Continued lack of appreciation for the significance of the Bethesda system-
      Proceedings from cytology courses organized in Wroclaw].

PMID- 11455938
TI  - Conflict from within.

PMID- 11455939
TI  - Static and dynamic pressure-volume curves reflect different aspects of
      respiratory system mechanics in experimental acute respiratory distress syndrome.
AB  - INTRODUCTION: A lower inflection point, an upper inflection (or deflection)
      point, and respiratory system compliance can be estimated from an inspiratory
      static pressure-volume (SPV) curve of the respiratory system. Such data are often
      used to guide selection of positive end-expiratory pressure (PEEP)/tidal volume
      combinations. Dynamic pressure-volume (DPV) curves obtained during tidal
      ventilation are effortlessly displayed on modern mechanical ventilator monitors
      and bear a theoretical but unproven relationship to the more labor-intensive SPV
      curves. OBJECTIVE: Attempting to relate the SPV and DPV curves, we assessed both
      curves under a range of conditions in a canine oleic acid lung injury model.
      METHODS: Five mongrel dogs were anesthetized, paralyzed, and monitored to assure
      a stable preparation. Acute lung injury was induced by infusing oleic acid. SPV
      curves were constructed by the super-syringe method. DPV curves were constructed
      for a range of PEEP and inspiratory constant flow settings while ventilating at a
      frequency of 15 breaths/min and tidal volume of 350 mL. Functional residual
      capacity at PEEP = 0 cm H2O was measured by helium dilution. The change in lung
      volume by PEEP at 8, 16, and 24 cm H2O was measured by respiratory inductance
      plethysmography. RESULTS: The slope of the second portion of the DPV curve did
      not parallel the corresponding slope of the SPV curve. The mean lower inflection
      point of the SPV curve was 13.2 cm H2O, whereas the lower inflection point of the
      DPV curve was related to the prevailing flow and PEEP settings. The absolute lung
      volume during the DPV recordings exceeded (p < 0.05) that anticipated from the
      SPV curves by (values are mean +/- SEM) 267 +/- 86 mL, 425 +/- 129 mL, and 494 +/
      129 mL at end expiration for PEEP = 8, 16, and 24 cm H2O, respectively.
      CONCLUSIONS: The contours of the SPV curve are not reflected by those of the DPV
      curve in this model of acute lung injury. Therefore, this study indicates that
      DPV curve should not be used to guide the selection of PEEP/tidal volume
      combinations. Furthermore, an increase in end-expiratory lung volume occurs
      during tidal ventilation that is not reflected by the classical SPV curve,
      suggesting a stable component of lung volume recruitment attributable to tidal
      ventilation, independent of PEEP.

PMID- 11455940
TI  - [Examination of individuals soliciting and possessing permission for firearms-
      questions and considerations for medical practice].

PMID- 11455941
TI  - Primary angiosarcoma of the femur: a diagnostic dilemma with a rare bone tumour.
AB  - We describe a rare case of high-grade primary angiosarcoma of the proximal femur
      in a 66-year-old man that proved fatal secondary to pulmonary metastases. The
      difficulties experienced in histological and immunohistochemical diagnosis of
      these tumours, and the resultant need for a high index of suspicion by surgeons
      in general and orthopaedists dealing with bone tumours in particular, is
      emphasized, as is the need for multidisciplinary management.

PMID- 11455942
TI  - Two sacred cows of neonatal intensive care.

PMID- 11455943
TI  - Using a modified nasopharyngeal airway in Pierre Robin syndrome.

PMID- 11455944
TI  - Staff perception of pain on a neonatal intensive care unit.

PMID- 11455945
TI  - Use of the black area on the tubetip for rapid estimation of insertional depth of
      endotracheal tubes in neonates: a potential hazard.

PMID- 11455946
TI  - Respiratory distress syndrome and antenatal corticosteroid treatment in premature
      twins.

PMID- 11455947
TI  - So what happened to alosetron?

PMID- 11455948
TI  - Miracle laxative?

PMID- 11455949
TI  - Deleterious consequences of allogenic blood transfusion on postoperative
      infection: really a transfusion-related immunomodulation effect?

PMID- 11455950
TI  - Relationship between HLA alleles and cytomegalovirus infection after allogenic
      hematopoietic stem cell transplant.

PMID- 11455951
TI  - Molecular mechanism of brain injury and oedema.

PMID- 11455952
TI  - A Brief Review of the Previous International Brain Oedema Symposia.

PMID- 11455953
TI  - Ocular findings in distal arthrogryposis.

PMID- 11455954
TI  - Isolation and characterization of the human homeobox gene HOX D1.
AB  - Homeobox genes, first identified in Drosophila, encode transcription factors that
      regulate embryonic development along the anteroposterior axis of an organism.
      Vertebrate homeobox genes are described on the basis of their homology to the
      genes found within the Drosophila Antennapedia and Bithorax homeotic gene
      complexes. Mammals possess four paralogous homeobox (HOX) gene clusters, HOX A,
      HOX B, HOX C and HOX D, each located on different chromosomes, consisting of 9 to
      11 genes arranged in tandem. We report the characterization of the human HOX D1
      gene. This gene consists of two exons, encoding a 328 amino acid protein,
      separated by an intron of 354 bp. The human HOX D1 protein is one amino acid
      longer (328 amino acids) than the mouse protein (327 amino acids) and is 82%
      identical to the mouse HOX D1 homolog. The DNA binding homeodomain region of the
      human protein exhibits a 97% and 80% identity between mouse Hoxd1 and Drosophila
      labial homeodomains, respectively. The exon/intron and intron/exon splice
      junctions are conserved in position between human and mouse genes. Determination
      of the human HOX D1 gene structure permits the use of PCR based analysis of this
      gene for the assessment of mutations, for diseases that link to the HOXD cluster
      (such as Duanes Retraction Syndrome (DRS)), or polymorphisms associated with
      human variation. Molecular characterization of the HOXD1 gene may also permit
      analysis of the functional role of this gene in human neurogenisis.

PMID- 11455955
TI  - HAM: a new epitope-tag for in vivo protein labeling.
AB  - The ability to metabolically label proteins with 35S-methionine is critical for
      the analysis of protein synthesis and turnover. Despite the importance of this
      approach, however, efficient labeling of proteins in vivo is often limited by a
      low number of available methionine residues, or by deleterious side-effects
      associated with protein overexpression. To overcome these limitations, we have
      created a methionine-rich variant of the widely used HA tag, called HAM, for use
      with ectopically expressed proteins. Here we describe the development of a series
      of vectors, and corresponding antisera, for the expression and detection of HAM
      tagged proteins in mammalian cells. We show that the HAM tag dramatically
      improves the sensitivity of 35S-methionine labeling, and permits the analysis of
      Myc oncoprotein turnover even when HAM-tagged Myc is expressed at levels
      comparable to that of the endogenous protein. Because of the improved sensitivity
      provided by the HAM tag, the vectors and antisera described here should be useful
      for the analysis of protein synthesis and destruction at physiological levels of
      protein expression.

PMID- 11455956
TI  - Structure characterization of human RalGDS gene, and the identification of its
      novel variant.
AB  - RalGDS is a guanine nucleotide dissociation stimulator for Ral, which is a member
      of the Ras GTPase superfamily that regulates cellular proliferation,
      differentiation and transformation by mediating multiple signal transduction
      pathways. RalGDS can specifically promote the conversion from an inactive GDP
      bound state to an active GTP-bound state for Ral. The cDNA of human RalGDS has
      been cloned recently. In this paper, by comparison between the gene's genomic and
      cDNA seqence, we determined the structure of the gene, which showed that the
      reported human RalGDS transcribed from 18 exons. Furthermore, a novel variant of
      RalGDS that codes for a protein with a different N-terminus was cloned and
      identified. Northern hybridization revealed that the novel transcript was of 6.0
      kb in length while the transcript previously reported is of 4.0 kb. Both
      transcripts were ubiquitously expressed in human adult tissues examined, albeit
      with different amounts. In addition, this novel transcript was proved to be
      caused by employment of a new exon, designated as exon 1a, instead of the one,
      designated as exon 1b, in the reported cDNA. Thus, the RalGDS gene consists of at
      least 19 exons and spanned a 44 kb region. The length between exon 1a and exon 2
      was 33 kb, while the length between exon 1b and exon 2 was 8.8 kb.

PMID- 11455957
TI  - Identification of functional PDZ domain binding sites in several human proteins.
AB  - TIP-15 was previously identified as a cellular protein that can bind to the C
      terminal end of the HTLV-1 Tax protein via its two PDZ domains. The sequence of
      the N-terminal part of TIP-15 is identical to that of the synaptic protein PSD
      95. Both proteins are likely to be produced from the same gene by alternative
      splicing. Whereas expression of the PSD-95 mRNA was detected only with brain
      RNAs, that of TIP-15 was detected with RNAs from thymus, brain, skeletal muscle
      and Jurkat cells. The TIP-15 protein exhibits an apparent molecular weight of 40
      kD and is weakly expressed in T cell lines. A two-hybrid screen performed with
      TIP-15 as bait revealed the presence of a PDZ binding site (PDZ-BS) in the
      following proteins: Lysyl tRNA synthetase, 6-phosphogluconolactonase (6-GPL),
      Stress-activated protein kinase 3 (SAPK3), NET-1, Diacylglycerol kinase zeta,
      MTMR1, MCM7, and hSec8. The sequence at the C-terminal ends of these proteins
      matches the X-S/T-X-V-COOH consensus previously defined for PDZ-BSs, with the
      exception of 6-GPL and SAPK3 which include a leucine as the C-terminal residue.
      For Lysyl tRNA synthetase, NET1, MTMR1 and hSec8, binding to TIP-15 was confirmed
      by co-immunoprecipitation experiments performed with the extracts of transfected
      COS7 cells. These results show the existence of functional PDZ-BSs in these
      proteins, but future studies will be necessary to establish whether or not TIP-15
      represents a physiological partner. The significance of the presence of a PDZ-BS
      in these various proteins is discussed with respect to their function.

PMID- 11455958
TI  - Novel methylation at GpC dinucleotide in the fish Sparus aurata genome.
AB  - To date, vertebrate DNA has been found methylated at the 5' position of cytosine
      exclusively in dinucleotide CpG or CpNpG stretches. On the the other hand, we
      determined that cytosine was methylated unusually in dinucleotide GpC at 5'-GGCC
      3' sequences in the teleost Sparus aurata EcoRI satellite DNA family. This
      finding is the first example of methylated GpC sequences in the eukaryotic
      genomes. At this regard, we have examined the relative methylation levels at this
      site of the highly repetitive EcoRI satellite DNA family from Sparus aurata
      different tissues. The EcoRI repeat was remarkably more methylated in male germ
      cells but hypomethylated in female germ cells at the Hae III restriction site
      (GpC). The novel modification and the differential methylation pattern suggest
      that EcoRI satellite could have a structural and/or functional role at the
      centromeres of Sparus aurata.

PMID- 11455959
TI  - Effects of steroid hormones on age-related expression and modulation of the
      lysozyme gene of the oviduct of Japanese quail.
AB  - The expression of lysozyme gene in the oviduct of Japanese quail is age
      dependent. Here we show that the expression of the gene is altered by three
      steroid hormones: 17beta-estradiol (E), progesterone (P) and glucocorticoid
      (dexamethasone, G), and their combinations E+P, E+G and P+G. We also show that
      the levels/affinities of transacting factors that bind to specific cis-acting
      elements in the promoter region of the gene change with age and after steroid
      administration. These factors are sequence-specific, age and steroid-dependent.
      It is proposed that administration of appropriate doses of steroid hormones after
      adulthood may extend the reproductive function and egg laying period in birds.

PMID- 11455960
TI  - Cloning, tissue expression pattern and genomic organization of latexin, a human
      homologue of rat carboxypeptidase A inhibitor.
AB  - Latexin, a carboxypeptidase A inhibitor, is expressed in a cell type-specific
      manner in both central and peripheral nervous systems in the rat. It is used as a
      molecular marker for the regional specification of the neocortex. In this study,
      a cDNA was isolated from a human fetal brain cDNA library. The cDNA (LXN)
      contains an open reading frame encoding 222 amino acids. The comparison between
      the deduced amino acid sequences of LXN and latexins of rat and mouse revealed
      high sequence identity (84.2 and 84.7%, respectively). Northern blot analysis
      showed that LXN was expressed as a transcript of 1.3 kb in 15 out of 16 tissues
      examined, except in peripheral blood leukocyte. The expression levels were high
      in heart, prostate, ovary, kidney, pancreas, and colon, moderate or low in other
      tissues including brain. It is noteworthy that the tissue distribution of human
      LXN differs greatly to that of its homologue in the model animal, rat latexin. In
      addition, the LXN gene contains at least 6 exons and spans 5.9 kb according to
      the genomic sequence of the clone RP11-79M21 and the gap sequence cloned in this
      paper. LXN was assigned to 3q25-q26.2 according to the position of the marker
      SHGC-35682 found adjacent to LXN gene.

PMID- 11455961
TI  - An international survey of unrelated umbilical cord blood banking.
AB  - OBJECTIVES: To investigate operational and technical practices within the field
      of cord blood banking. MATERIALS AND METHODS: Cord blood banks world-wide were
      invited to participate in a survey of collection, processing and testing. The
      survey covered a 12-month period up to August 1998. RESULTS: Replies were
      received from 18 cord blood banks. Analysis of the survey responses demonstrated
      wide variations in many aspects of cord blood banking. CONCLUSION: There is a
      need for standardization to ensure adoption of best practice.

PMID- 11455962
TI  - Angiogenic effect of thymidine phosphorylase on macrophages in glioblastoma
      multiforme.
AB  - OBJECT: Thymidine phosphorylase (TP) and vascular endothelial growth factor
      (VEGF) are known angiogenic factors; however, there are few reports in which the
      relationship between these two factors is addressed. The authors compared
      expression patterns of TP and VEGF and investigated their role in the
      angiogenesis of glioblastoma multiforme (GBM). METHODS: Surgical specimens from
      41 cases of GBM were immunohistochemically stained for TP, VEGF, CD68 (a
      macrophage marker), and CD31 (an endothelial cell marker). Both TP labeling
      indices and VEGF immunoreactivity displayed significant correlations with
      vascular density. Although VEGF was diffusely distributed in the tumor, TP was
      strongly expressed around blood vessels and in vascular proliferation. Double
      labeling for TP and CD68 in 10 cases indicated that cells that reacted strongly
      positive for TP were almost always macrophages, and only small numbers of CD68
      negative cells weakly expressed TP. The TP messenger (m)RNA expression was
      investigated using reverse transcription-polymerase chain reaction in six GBMs.
      All six specimens expressed TP mRNA. In addition, TP mRNA was detected in two of
      three groups of cultured GBM cells derived from surgical specimens. Macrophages,
      the production of which was induced from two volunteers' peripheral blood
      monocytes by applying macrophage colony-stimulating factor, also expressed TP
      mRNA. The glioma cell lines U251MG and U87MG, which barely express TP mRNA under
      normal conditions, expressed TP mRNA in response to interferon-beta stimulation
      or while in an anoxic condition. CONCLUSIONS: Although it is feasible that GBM
      cells can express TP depending on their growing conditions, the majority of TP
      expressing cells present in GBMs appear to be infiltrating macrophages.
      Coexistence of VEGF and TP may indicate a synergistic upregulation for
      angiogenesis because VEGF exerts a chemotactic activity on macrophages that
      express TP.

PMID- 11455963
TI  - Protein-RNA interactions in the subunits of human nuclear RNase P.
AB  - A yeast three-hybrid system was employed to analyze interactions in vivo between
      H1 RNA, the RNA subunit of human nuclear RNase P, and eight of the protein
      subunits of the enzyme. The genetic analysis indicates that subunits Rpp21,
      Rpp29, Rpp30, and Rpp38 interact directly with H1 RNA. The results of direct UV
      crosslinking studies of the purified RNase P holoenzyme confirm the results of
      the three-hybrid assay.

PMID- 11455964
TI  - Prediction of a common fold for all four subunits of the yeast tRNA splicing
      endonuclease: implications for the evolution of the EndA/Sen   family.

PMID- 11455965
TI  - The new MCAT and medical student performance.
AB  - The "old" Medical College Admission Test (MCAT) has been replaced by the "new"
      MCAT. For many years the University of California, Irvine, has included the old
      MCAT in a prediction index as part of its admissions procedure. The use of the
      New MCAT has required this index to be recalculated. Since the predictive power
      of the new MCAT is unknown, it has been necessary to wait until the first class
      admitted completed its freshman year. This paper is an analysis of the new MCAT
      and its relationship to the criterion of class standing achieved in the school
      year ending in the spring of 1979.

PMID- 11455966
TI  - Hebbian learning reconsidered: representation of static and dynamic objects in
      associative neural nets.
AB  - According to Hebb's postulate for learning, information presented to a neural net
      during a learning session is stored in synaptic efficacies. Long-term
      potentiation occurs only if the postsynaptic neuron becomes active in a time
      window set up by the presynaptic one. We carefully interpret and mathematically
      implement the Hebb rule so as to handle both stationary and dynamic objects such
      as single patterns and cycles. Since the natural dynamics contains a rather broad
      distribution of delays, the key idea is to incorporate these delays in the
      learning session. As theory and numerical simulations show, the resulting
      procedure is surprisingly robust and faithful. It also turns out the pure Hebbian
      learning is by selection: the network produces synaptic representations that are
      selected according to their resonance with the input percepts.

PMID- 11455967
TI  - Inhibition of FLT3-mediated transformation by use of a tyrosine kinase inhibitor.
AB  - FLT3 is a member of the type III receptor tyrosine kinase (RTK) family. These
      receptors all contain an intrinsic tyrosine kinase domain that is critical to
      signaling. Aberrant expression of the FLT3 gene has been documented in both adult
      and childhood leukemias including AML, ALL and CML. In addition, 17-27% of
      pediatric and adult patients with AML have small internal tandem duplication
      mutations in FLT3. Patients expressing the mutant form of the receptor have been
      shown to have a decreased chance for cure. Our previous study, using a
      constitutively activated FLT3, demonstrated transformation of Ba/F3 cells and
      leukemic development in an animal model. Thus, there is accumulating evidence for
      a role for FLT3 in human leukemias. This has prompted us to search for inhibitors
      of FLT3 as a possible therapeutic approach in these patients. AG1296 is a
      compound of the tyrphostin class that is known to selectively inhibit the
      tyrosine kinase activity of the PDGF and KIT receptors. Since FLT3 is a close
      relative of KIT, we wanted to test the possible inhibitory activity of AG1296 on
      FLT3. In transfected Ba/F3 cells, AG1296 selectively and potently inhibited
      autophosphorylation of FL-stimulated wild-type and constitutively activated FLT3.
      Treatment by AG1296 abolished IL-3-independent proliferation of Ba/F3 cells
      expressing the constitutively activated FLT3 and thus, reversed the
      transformation mediated by activated FLT3. Inhibition of FLT3 activity by AG1296
      in cells transformed by activated FLT3 resulted in apoptotic cell death, with no
      deleterious effect on their parental counterparts. Addition of IL-3 rescued the
      growth of cells expressing activated FLT3 in the presence of AG1296. This
      demonstrates that the inhibition is specific to the FLT3 pathway in that it
      leaves the kinases of the IL-3 pathway and other kinases further downstream
      involved in proliferation intact. Several proteins phosphorylated by the
      activated FLT3 signaling pathway, including STAT 5A, STAT 5B and CBL, were no
      longer phosphorylated when these cells were treated with AG1296. The activity
      against FLT3 suggests a potential therapeutic application for AG1296 or similar
      drugs in the treatment of leukemias involving deregulated FLT3 tyrosine kinase
      activity and as a tool for studying the biology of FLT3.

PMID- 11455968
TI  - Suppression of apoptosis: role in cell growth and neoplasia.
AB  - A cell is a potentially dangerous thing. In unicellular organisms, cells divide
      and multiply in a manner that is chiefly determined by the availability of
      nutritional substrates. In a multicellular organism, each cell has a distinct
      growth potential that is designed to subsume a role in the function of the whole
      body. Departure from this path to one of uncontrolled cellular proliferation
      leads to cancer. For this reason, evolution has endowed cells with an elaborate
      set of systems that cause errant cells to self-destruct. This process of cell
      suicide is known as apoptosis or programmed cell death and it plays a crucial
      role in the growth of both normal and malignant cells. In this review, we
      describe the mechanisms whereby programmed cell death is induced and executed. In
      particular, we concentrate on how anti-apoptotic signals generated by cytokines
      promote cell survival and how these signal transduction pathways may be involved
      in the pathogenesis of neoplasia. Understanding how these processes contribute to
      tumorigenesis may suggest new therapeutic options.

PMID- 11455969
TI  - The kiss of death: promises and failures of death receptors and ligands in cancer
      therapy.
AB  - Death receptors and their ligands exert important regulatory functions in the
      maintenance of tissue homeostasis and the physiological regulation of programmed
      cell death. Currently, six different death receptors are known including tumor
      necrosis factor (TNF) receptor-1, CD95 (Fas/APO-1), TNF receptor-related
      apoptosis-mediating protein (TRAMP), TNF-related apoptosis-inducing ligand
      (TRAIL) receptor-1 and -2, and death receptor-6 (DR6). The signaling pathways by
      which these receptors induce apoptosis are similar and rely on oligomerization of
      the receptor by death ligand binding, recruitment of an adapter protein through
      homophilic interaction of cytoplasmic domains, and subsequent activation of an
      inducer caspase which initiates execution of the cell death programme. The
      ability of these receptors and their ligands to kill malignant cells was
      discovered early and helped to coin the term 'tumor necrosis factor' for the
      first identified death ligand. This review summarizes the current and rapidly
      expanding knowledge about the signaling pathways triggered by death
      receptor/ligand systems, their potency in experimental cancer therapy, and their
      therapeutic limitations, especially regarding their toxicity for non-malignant
      cells.

PMID- 11455970
TI  - Current recommendations for positive controls in RT-PCR assays.
AB  - The choice of adequate controls for reverse transcriptase (RT-) PCR analysis has
      been the focus of a debate pursued in Leukemia over the past 3 years. Twenty-six
      authors from 15 different centers contributed to the Debate, and the points
      presented have been carefully evaluated. This survey reviews the issues
      discussed, and presents current options for appropriate positive controls in RT
      PCR assays which are based on the views shared by the majority of participants in
      the Debate. It is understood, however, that the recommendations presented cannot
      be regarded as definitive guidelines. They reflect the present state of
      knowledge, and certainly need to be revisited.

PMID- 11455971
TI  - A comparison of early intensive methotrexate/mercaptopurine with early intensive
      alternating combination chemotherapy for high-risk B-precursor acute
      lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial.
AB  - A prospective, randomized multicenter study was performed to evaluate the
      relative efficacy of two different concepts for early intensive therapy in a
      randomized trial of children with B-precursor acute lymphoblastic leukemia (ALL)
      at high risk (HR) for relapse. Four hundred and ninety eligible children with HR
      ALL were randomized on the Pediatric Oncology Group (POG) 9006 phase III trial
      between 7 January 1991 and 12 January 1994. After prednisone (PDN), vincristine
      (VCR), asparaginase (ASP) and daunorubicin (DNR) induction, 470 patients received
      either 12 intensive parenteral treatments of intermediate dose (1 g/m2 each)
      methotrexate (MTX) and mercaptopurine (MP) over 24 weeks (regimen A) or 12
      intensive course of alternating myelosuppressive drug combinations given over 30
      weeks (regimen B). These drug combinations included MTX/MP, teniposide (VM
      26)/cytosine arabinoside (AC) and VCR/PDN/DNR/AC/ASP. Central nervous system
      (CNS) prophylaxis was age-adjusted triple intrathecal chemotherapy. Patients with
      CNS disease at diagnosis were treated with craniospinal irradiation after the
      intensive phase. Continuation was standard doses of MTX and MP for 2 years. This
      trial was closed early because of an apparent early difference favoring regimen
      B. Results show that 470 patients achieved remission (97%). Two hundred and
      thirty two were randomized to regimen A and 238 to regimen B. The estimated 4
      year event-free survival (EFS) for patients treated with regimen A is 61.6 %
      (s.e. = 3.3%) and with regimen B is 69.4% (s.e. = 3.1%), P = 0.091. Toxicities
      were more frequent on regimen B. In conclusion, for children with B-precursor ALL
      at high risk to relapse, early intensification with myelosuppressive combination
      chemotherapy was more toxic but produced no significant difference in EFS when
      compared to those treated with parenteral methotrexate and mercaptopurine.

PMID- 11455972
TI  - Improved prognostic significance of cytokine-induced proliferation in vitro in
      patients with de novo acute myeloid leukemia of intermediate risk: impact of
      internal tandem duplications in the Flt3 gene.
AB  - The heterogeneity of acute myeloid leukemia is reflected in many clinical,
      biological and genetic features that are used to predict the response to therapy.
      On the basis of chromosome aberrations patients can be stratified in groups
      reflecting either good or poor prognosis. However, the majority of patients fall
      in an 'intermediate risk' group. Internal tandem duplications in the
      hematopoietic growth factor receptor Flt3 have been shown to separate a subset of
      high risk patients from intermediate or low risk cases. In an attempt to further
      characterize the heterogeneity of prognosis among the cytogenetic intermediate
      risk group of AML, we investigated the overall survival, failure-free survival,
      initial therapy response and relapse rates of 103 patients with de novo AML in
      relation to autonomous proliferation and the proliferative response to a panel of
      10 cytokines in a short-term thymidine incorporation assay. To exclude
      perturbation of the responses by other (known) risk factors our final
      intermediate risk population was comprised of patients with intermediate risk
      cytogenetics, having an age of 60 years of younger and not showing tandem
      duplications in the Flt3 gene. Among this intermediate risk group, only the
      responses to M-CSF and IL-1alpha were found to be predictive for therapy outcome.
      Results obtained by a 7-day culture with these cytokines revealed two
      subpopulations characterized by a good and a poor prognosis, respectively. The
      complete remission rates in these subpopulations were similar, but the relapse
      rates, failure-free survival and overall survival differed. If further study
      extends and supports our data, it should be considered to include these patients
      in the poor risk arms of treatment protocols and offer them intensified treatment
      or bone marrow transplantation.

PMID- 11455973
TI  - Prognostic significance of p16INK4a immunocytochemistry in adult ALL with
      standard risk karyotype.
AB  - The p16INK4a gene is frequently inactivated in acute lymphoblastic leukemia
      (ALL), by homozygous deletion. However, p16INK4a protein expression also varies
      widely in ALL blasts. We investigated the p16INK4a protein expression by
      immunocytochemistry (ICC) analysis in 76 cases adult ALL. We observed a great
      variation of the percentage of ICC-positive leukemic cells between samples even
      in which FISH analysis did not find p16INK4a gene deletion. All patients carrying
      a p16INK4a gene homozygous deletion were also negative by ICC. ALL with negative
      p16INK4a ICC were more frequently of T lineage, but no significant differences
      for white blood cell count, presence of bulky disease, karyotype, hemoglobin
      level, complete remission rate, overall and event-free survival (EFS) were found.
      However overall survival and EFS were significantly lower in patients negative by
      ICC, when analysis was performed in ALL with standard risk karyotype. We also
      analyzed sequentially at diagnosis and relapse nine cases and observed that one
      case lost p16INK4a expression between diagnosis and relapse, but that on the
      contrary three other samples showed increased expression at relapse. These
      findings suggest that p16INK4a ICC and deletion analysis provide distinct
      information about ALL cells and that the simple ICC method may be of prognostic
      value in standard risk adult ALL.

PMID- 11455974
TI  - Monitoring minimal residual disease and predicting relapse in APL by quantitating
      PML-RARalpha transcripts with a sensitive competitive RT-PCR method.
AB  - Qualitative RT-PCR methods used for monitoring minimal residual disease (MRD) in
      APL patients fail to predict relapse in up to 25% of patients in remission. We
      report here the development and evaluation of a highly sensitive (10(-5) and 10(
      6) with one round and two rounds of PCR, respectively) competitive RT-PCR method
      to quantitate the PML-RARalpha fusion transcripts. PML-RARalpha transcript's
      levels were normalised to 10(5) copies of ABL transcript. Serial BM and PB
      samples from 16 patients with APL and t(15;17) were examined. Presentation
      samples from three patients (three BM, one PB) showed levels in the range of 0.7
      x 10(6)-3.5 x 10(6) and 1.2 x 10(5) molecules in BM and PB samples respectively.
      Serial quantitation of MRD in both BM and PB samples showed significantly lower
      levels of PML-RARalpha transcripts in remission, although the majority of samples
      remain positive for the PML-RARalpha transcripts even those in long-term
      remission (up to 94 months). Levels of PML-RARalpha in remission samples were up
      to 2 x 10(2) and up to 5.2 x 10(1) molecules in BM and PB respectively. BM and PB
      samples taken from two patients 2-4 months before relapse showed significantly
      higher levels of PML-RARalpha transcripts (1.2 x 10(4) molecules in BM; 3.5 x
      102, 1.2 x 10(2) and 1.2 x 10(3) in PB). The same samples, when tested with a
      standard qualitative RT-PCR for the amplification of PML-RARalpha (with a
      sensitivity of 10(-4)) produced negative results. This indicates that the
      qualitative methods would not have predicted relapse in these patients. Our data
      show that quantitating PML-RARalpha transcripts with a sensitive method may
      provide a superior approach for monitoring MRD in APL and identifying patients at
      high risk of relapse.

PMID- 11455975
TI  - Post-induction residual leukemia in childhood acute lymphoblastic leukemia
      quantified by PCR correlates with in vitro prednisolone resistance.
AB  - Most prognostic factors in childhood acute lymphoblastic leukemia (ALL) are
      informative for groups of patients, whereas new approaches are needed to predict
      the efficacy of chemotherapy for the individual patient. The residual leukemia
      following 4 weeks of induction therapy with prednisolone, vincristine,
      doxorubicin and i.t. methotrexate and the in vitro resistance to prednisolone,
      vincristine, and doxorubicin were measured in 30 boys and 12 girls with B (n =
      34) or T lineage (n = 8) ALL. The residual leukemia was quantified after 2 (MRD
      D15, n = 29) and 4 weeks (MRD-PI, n = 42) of induction therapy with a precise and
      reproducible clone-specific PCR technique. The median MRD-D15 and MRD-PI were
      0.50% (75% range 0.0088.1%) and 0.014% (75% range 0.001-2.0%), respectively, and
      these levels correlated significantly (n = 29, rs = 0.75, P < 0.001). Both the
      MRD-D15 and the MRD-PI were related to the age of the patient (MRD-D15: rs= 0.48,
      P= 0.009; MRD-PI: rs = 0.45, P = 0.003). Patients with T lineage ALL had higher
      MRD-PI than those with B lineage ALL (median MRD-PI: 0.5% vs 0.01%, P = 0.05).
      The median LC50 (concentration lethal to 50% of cells) for prednisolone was 2.3
      microg/ml (75% range 0.05-668). Both MRD-D15 and MRD-PI correlated significantly
      with the in vitro resistance to prednisolone (MRD-D15: rs = 0.41, P = 0.03; MRD
      PI: rs = 0.39, P = 0.01); but not to in vitro vincristine or doxorubicin
      resistance. The correlations between MRD and in vitro prednisolone resistance
      were even more pronounced when B cell precursor and T cell leukemia were analyzed
      separately (B cell precursor ALL: MRD-PI vs prednisolone LC50: n = 33, rs = 0.47,
      P = 0.006; T cell ALL: MRD-PI vs prednisolone resistance: n = 8, rs = 0.84, P =
      0.009). After a median follow-up of 5.0 years (75% range 3.2-6.9) eight patients
      have relapsed. All of the 21 patients with a MRD-PI < or =0.5% and a prednisolone
      LC50 < or =10 microg/ml have remained in remission whereas the 7 year event-free
      survival for the remaining 20 patients was 0.45 +/- 0.16 (P= 0.002) Prospective
      studies in childhood ALL are needed to clarify whether combined monitoring of in
      vitro drug resistance and residual leukemia early during chemotherapy could offer
      new ways to classify patients and stratify the intensity of therapy.

PMID- 11455976
TI  - Quantification of CBFbeta/MYH11 fusion transcript by real time RT-PCR in patients
      with INV(16) acute myeloid leukemia.
AB  - Amplification of the CBFbeta/MYH11 fusion transcript by a qualitative reverse
      transcription-polymerase chain reaction (RT-PCR) has been used to detect minimal
      residual disease (MRD) and assess the risk for disease relapse in inv(16)(p13q22)
      acute myeloid leukemia (AML). This strategy has, however, produced conflicting
      results and because of an uncertain predictive value, its use in the clinical
      setting cannot be recommended. The objective of the current study was to evaluate
      if quantification by Real Time RT-PCR could be useful to determine levels of
      CBFbeta/MYH11 fusion transcripts predictive of clinical outcome in
      inv(16)(p13q22) AML at diagnosis or during remission. Bone marrow (BM) samples
      from 16 patients with inv(16) AML enrolled on a German multicenter trial (AML
      HD93) were analyzed for levels of CBFbeta/MYH11 fusion transcripts by Real Time
      RT-PCR at diagnosis (n= 14), during remission (n= 10) and at relapse (n=6). The
      CBFbeta/MYH11 transcript copy number in each sample was normalized to copies of
      an internal control housekeeping transcript (ie 18S). The copy number measured at
      diagnosis or relapse were 3 to 4 log higher that those measured during remission,
      following completion of induction treatment. A high CBFbeta/MYH11 transcript copy
      number at diagnosis had a significant correlation with a high percentage of BM
      blasts (Spearman's coefficient = -0.66; P= 0.03), and a borderline correlation
      with a short complete remission (CR) duration (Spearman's coefficient = -0.51; P=
      0.07). No difference in levels of CBFbeta/MYH11 fusion transcripts measured
      during intensification therapy was found between patients destined to relapse and
      those who continued in CCR (P= 0.75). Following completion of the entire
      chemotherapy program, patients that during CR showed a CBFbeta/MYH11 fusion
      transcript copy number >10 had a significantly shorter CR duration (P= 0.002) and
      higher risk for disease relapse (P= 0.05) than patients with a CBFbeta/MYH11
      fusion transcript copy number <10. The results of the current study, therefore,
      suggest that it is possible to determine in remission samples a threshold of
      CBFbeta/MYH11 transcript copy number above which relapse occurs and below which
      continuous CR is likely.

PMID- 11455977
TI  - The association of the TEL-AML1 chromosomal translocation with the accumulation
      of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B
      progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.
AB  - Lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia
      (BpALL) with chromosomal hyperdiploidy and with translocations affecting
      chromosome 12p11-13, accumulate high and low levels of methotrexate
      polyglutamates (MTXPGs), respectively. Recently a cryptic translocation, t(12;21)
      (p13;q22), has been demonstrated by molecular and fluorescence in situ
      hybridization techniques in this disease. The chimeric TEL-AML1 transcript, which
      has been associated with this translocation, can be detected in up to 25% of
      children with BpALL. We detected the TEL-AML1 and/or the AML1-TEL transcript in
      30 (33%) of 91 patients studied. Levels of lymphoblast MTXPGs were lower in those
      with than in those without the TEL-AML1 translocation (P = 0.004). Hyperdiploidy
      was rare in lymphoblasts with the TEL-AML1 translocation (P = 0.047). Both ploidy
      (P= 0.0015) and TEL-AML1 status (P= 0.0043) were independently and significantly
      correlated with the log of the lymphoblast MTXPG level. However, the presence of
      TEL-AML1 or of hyperdiploidy accounted for only 22% of the variation of this
      value. Our results imply that each of 1.16 > or = DI and the presence of the TEL
      AML1 translocation confers a 50% decrease in lymphoblast MTXPG level. When
      planning reduction of therapy for either of the two excellent outcome categories
      of hyperdiploid or TEL-AML1 BpALL, one should consider the difference between
      these two subgroups in the ability of lymphoblasts to accumulate MTXPGs.

PMID- 11455978
TI  - Serum TNFalpha levels in patients with acute graft-versus-host disease after bone
      marrow transplantation.
AB  - Tumor necrosis factor alpha (TNFalpha) has been implicated in the pathogenesis of
      graft-versus-host disease (GVHD). In this study, serum levels of TNFalpha were
      assessed by ELISA in 243 sera samples from 40 patients who had undergone
      allogeneic bone marrow transplantation (BMT). Serum TNFalpha levels were measured
      before BMT and at different time points after BMT. The results were correlated
      with acute GVHD (aGVHD), infection and conditioning regimen. Serum TNFalpha
      levels were significantly higher in patients with grades II-IV aGVHD than in
      those with grade 0 or I aGVHD, but there was no clear correlation between serum
      TNFalpha and severity of aGVHD. Serum TNFalpha levels in infected patients were
      not statistically different from those in patients without infection. The
      conditioning regimen did not cause a significant rise in TNFalpha levels. These
      results indicate that TNFalpha may be useful for the diagnosis of aGVHD and for
      differentiating between aGVHD and other BMT-related complications, such as
      infection.

PMID- 11455979
TI  - NOD/SCID repopulating cells but not LTC-IC are enriched in human CD34+ cells
      expressing the CCR1 chemokine receptor.
AB  - Human haemopoietic stem and progenitor cells may be distinguished by the pattern
      of cell surface markers they display. The cells defined as 'stem' cells are
      heterogeneous and lack specific markers for their detection. However, they may be
      identified in in vitro assays such as the long-term culture initiating cell (LTC
      IC) and in transplant assays involving immunosuppressed NOD/SCID mice. It is
      still not clear to what extent, if any, these cell populations overlap. The
      chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) prolongs survival
      of LTC-IC in suspension cultures and we now show that in longterm bone marrow
      cultures (LTBMC) maintenance of haemopoiesis was significantly better from the
      CD34+ cells which possess MIP-1alpha receptors (P < 0.006). We examined one MIP
      1alpha receptor, CCR1, which is present on CD34+ cells from haemopoietic tissues.
      In LTBMC the production of GM-CFC from CD34+CCR1- cells was significantly higher
      (P < 0.02) than that from CD34+CCR1+ cultures and the incidence of LTC-IC was 3-
      to 6-fold higher in the CD34+CCR1- cell fraction. In contrast, the cells
      responsible for high levels of engraftment in NOD/SCID mice were contained in the
      CD34+CCR1+ cell fraction. The CD34+CCR1+ cells engrafted to high levels in
      NOD/SCID and generated large numbers of progenitor cells. Therefore, we conclude
      that LTC-IC and SRC may be distinguished on the basis of expression of the
      chemokine receptor CCR1.

PMID- 11455980
TI  - The promotion of plasmacytoma tumor growth by mesenchymal stroma is antagonized
      by basic fibroblast growth factor induced activin A.
AB  - The mesenchymal stroma has been shown to play a crucial role in the development
      of multiple myeloma, partly by secretion of interleukin (IL)-6, that serves as a
      growth factor for myeloma cells. However, it is still unclear which other stromal
      molecules are involved in the pathogenesis of this disease. We chose, as a model
      system, a mouse plasmacytoma cell line, which does not respond to IL-6. We found
      that the formation of mouse plasmacytoma tumors, in an in vivo skin
      transplantation model, is facilitated by co-injection of these tumor cells along
      with a mesenchymal stromal cell. The tumor promoting effect of the stroma was
      reproduced in an in vitro model; stromal cells induced the proliferation of
      plasmacytoma cells under serum-free conditions. This growth promotion could not
      be mimicked by a series of cytokines including IL-6 and insulin-like growth
      factor (IGF)-I implying a role for yet unidentified stromal factors. The in vivo
      formation of plasmacytoma tumors was reduced following administration of activin
      A, a cytokine member of the transforming growth factor (TGF)beta superfamily.
      Furthermore, the in vitro growth promoting effect of the stroma was abrogated by
      basic fibroblast growth factor (bFGF) which induced a higher stromal expression
      of activin A. Our results thus show that mesenchymal stroma expresses
      plasmacytoma growth stimulating activities that overcome the low constitutive
      level of the plasmacytoma inhibitor, activin A. The expression of activin A is
      upregulated by bFGF rendering the stroma suppressive for plasmacytoma growth. The
      balance between the expression of these regulators may contribute to mesenchymal
      stroma activity and influence the progression of multiple myeloma.

PMID- 11455981
TI  - Apoptosis/differentiation-inducing effects of vitamin K2 on HL-60 cells:
      dichotomous nature of vitamin K2 in leukemia cells.
AB  - We originally reported that vitamin K2 (VK2) analogs, including menaquinone 4
      (MK4) but not vitamin K1, effectively induce apoptosis in various types of
      primary cultured leukemia cells and leukemia cell lines in vitro. It has also
      been reported by others that VK2 showed the differentiation-inducing activity in
      leukemia cell lines. To investigate the discrepancy between apoptosis- and
      differentiation-inductions of leukemia cells by VK2 treatment, we used bcl-2 gene
      transfected HL-60 cells (HL-60-bcl-2) which resulted in five-fold over-expression
      of BCL-2 protein, and then compared the effects of MK4 to the control HL-60-neo
      cells. Seventy-two hours of exposure to various concentrations of MK4 resulted in
      growth inhibition of these cells in a dose-dependent manner (0.1-50 microM),
      however, HL-60-bcl-2 was less sensitive against MK4. MK4 potently induced
      apoptosis of HL-60-neo cells along with the depolarization of mitochondrial
      membrane potential and caspase-3 activation. Notably, HL-60-bcl-2 was almost
      completely resistant to apoptosis induction in response to MK4, although cell
      growth inhibition was still observed. In spite of the abrogation of apoptosis
      induction, about 90% of HL-60-bcl-2 cells were arrested in the G0/G1 phase within
      48 h of exposure to 10 microM of MK4 accompanied by up-modulation of p27KIP1
      expression. Concomitantly, HL-60-bcl-2 cells underwent monocytic differentiation.
      These data suggest that VK2 also shows the differentiation inducing effects on
      leukemia cells which are resistant against VK2-inducing apoptosis. The
      dichotomous nature of VK2 against leukemia cells appears to have clinical
      benefits for the treatment of patients with leukemias and myelodysplastic
      syndromes.

PMID- 11455982
TI  - Final analysis of the ECOG I-COPA trial (E6484) in patients with non-Hodgkin's
      lymphoma treated with interferon alfa (IFN-alpha2a) plus an anthracycline-based
      induction regimen.
AB  - The Eastern Cooperative Oncology Group (ECOG) performed a prospectively
      randomized study (E6484) evaluating the use of interferon alfa 2a (IFN-alpha2a)
      in patients with aggressive low-grade or with intermediate-grade non-Hodgkin's
      lymphoma (NHL) accruing close to 300 patients between 1985 and 1988. Patients
      were eligible for study if they had bulky or symptomatic low-grade lymphoma or
      defined intermediate-grade subtypes. Of 291 patients enrolled, 249 were eligible
      for analysis. All patients were randomized to receive a four-drug cytotoxic
      chemotherapy regimen including cyclophosphamide, doxorubicin, vincristine and
      prednisone in 4-week cycles with or without IFN-alpha2a in addition (COPA vs I
      COPA). Treatment was given for up to 8-10 months. This report, at a time when the
      median follow-up among survivors has reached 12 years, updates the analysis of
      time to treatment failure (TTF), duration of disease-free survival (DFS), and
      overall survival. Patients randomized to receive IFN-alpha2a had a prolonged TTF
      (P= 0.008; median 2.4 vs 1.6 years). DFS for those patients who had complete
      responses was also longer if IFN-alpha2a had been given (P = 0.035; median 2.7 vs
      1.8 years). There was a clinically but not a statistically significant
      prolongation of overall survival by IFN-alpha2a (P= 0.107; median 7.8 vs 5.7
      years). There were fewer deaths over time due to lymphoma in patients receiving
      IFN-alpha2a (67 vs 80 deaths). A subset analysis, based on disease histology (low
      grade, follicular, intermediate-grade), revealed a significant prolongation of
      TTF in patients receiving IFN-alpha2a with either low-grade (P = 0.002; median
      2.4 vs 1.6 years) or follicular (P= 0.01; median 2.5 vs 1.7 years) NHL but not
      intermediate grade (P = 0.622; median 2.3 vs 1.6 years) NHL. This analysis,
      performed approximately 12 years after closure of the study to accrual, supports
      the addition of interferon alfa to an induction cytotoxic chemotherapy regimen
      including cyclophosphamide and doxorubicin in the treatment of follicular NHL.

PMID- 11455983
TI  - Early locoregional high-dose radiotherapy is associated with long-term disease
      control in localized primary angiocentric lymphoma of the nose and nasopharynx.
AB  - Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL)
      which generally carries a poor prognosis when treated with conventional NHL
      chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal
      NK/T cell lymphomas treated at our institution over a 29 year period. Median age
      was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70
      Gy) before 1980 and combination chemotherapy after 1980. Six patients were
      treated with first-line radiotherapy and they achieved complete remission (CR).
      Two subsequently received combination chemotherapy. Five of those patients
      remained in complete remission, after 97+ to 277+ months. Twelve patients were
      treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven
      cases, and COP in five cases. Only three of them achieved CR, five had partial
      response and four had progressive disease. Five of the seven patients treated
      with CHOP did not achieve complete remission. The nine patients who failed to
      achieve CR with chemotherapy subsequently received salvage radiotherapy but only
      two of them obtained CR. Finally, two patients were treated with alternated
      chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+
      months. Median survival was not reached in patients who received front-line
      radiotherapy, and was 35 months in patients who received front-line chemotherapy.
      These findings confirm that chemotherapy gives a low complete remission rate in
      localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to
      give favorable results, whereas its results are poorer when administered after
      resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy,
      or alternated chemotherapy-radiotherapy regimens give better clinical results
      than radiotherapy alone will have to be evaluated prospectively in this type of
      NHL.

PMID- 11455984
TI  - Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that
      myeloma IgM and IgA expressing subclones can originate from the IgG expressing
      tumour.
AB  - Isotype-switch variants can easily be detected in a significant proportion of
      multiple myeloma (MM) patients. The biological significance of these isotype
      switch variants remains obscure. Therefore, we studied the appearance of these
      isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG
      isotype. With a MM-specific PCR assay we could detect isotype-switch variants in
      the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again
      the close resemblance of this mouse model to the human MM. These isotype-switch
      variants were not found in an in vitro stroma-independent variant of the 5T33MM
      line. However, when this 5T33MMvitro line was injected into young syngeneic mice,
      isotype-switch variants appeared thereafter in the isolated tumour cells. These
      isotype-switch variants could only originate from the MM-IgG expressing cell
      since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch
      variants. The appearance of IgA cells can be explained by down-stream switching
      of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching
      to the sister chromatid as the Cmu region is deleted from the CIS-chromosome.
      This study demonstrates that isotype-switch variants originate from the major
      tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch
      precursor MM cell. The appearance of isotype-switch variants should be considered
      as a rare but normal event now becoming visible due to the high number of clonal
      cells present in MM.

PMID- 11455985
TI  - Further characterization of complex chromosomal rearrangements in myeloid
      malignancies: spectral karyotyping adds precision in defining abnormalities
      associated with poor prognosis.

PMID- 11455986
TI  - Abnormalities of the p16INK4a gene in childhood B-precursor acute lymphoblastic
      leukemia without nonrandom translocations: analysis of seven matched pairs of
      primary leukemia and corresponding cell line.

PMID- 11455987
TI  - Mutation study of the BCL10 gene in lymphoma with both RNA and DNA.

PMID- 11455988
TI  - The presence of somatic mutations in immunoglobulin genes of B cell acute
      lymphoblastic leukemia (ALL-L3) supports assignment as Burkitt's leukemia
      lymphoma rather than B-lineage ALL.

PMID- 11455989
TI  - The growth of highly proliferative acute lymphoblastic leukemia may be
      independent of stroma and/or angiogenesis.

PMID- 11455990
TI  - Challenges in advancing women's health in the 21st century: perspectives from the
      Office of Research on Women's Health.

PMID- 11455991
TI  - Postterm delivery among African Americans, Mexican Americans and Whites in
      Chicago.
AB  - OBJECTIVES: The purpose of the present study was to examine the effect of
      individual-level and community-level risk factors on the postterm delivery rates
      of infants born to African-American, Mexican-American, and non-Latino White
      mothers; and to compare postterm delivery rates between these ethnic groups.
      DESIGN: This is a population-based study. METHODS: We performed stratified and
      multivariate logistic regression analyses on a linked dataset of 1992-1995
      Illinois vital records, 1990 United States Census income data, and 1995 Chicago
      Department of Public Health information. Communities with one or more high-risk
      characteristics (low median family income or high rates of unemployment, homicide
      or lead poisoning) were classified as impoverished. RESULTS: In Chicago, African
      Americans (N = 85,978) had a postterm rate of 4.3/1,000 and Mexican Americans (N
      = 47,266) had a postterm rate of 3.6/1,000, compared to 2.3/1,000 for non-Latino
      Whites (N = 48,601); relative risk (ninety-five percent confidence interval) =
      1.9 (1.5-2.3) and 1.6 (1.2-2.0), respectively. Maternal age, education, marital
      status, parity, and prenatal care usage were associated with ethnic group
      specific postterm delivery rates. In a multivariate logistic regression model for
      non-impoverished mothers, the adjusted odds ratios of postterm delivery for
      African Americans and Mexican Americans were 1.0 (0.5-3.2) and 1.0 (0.6-1.7),
      respectively. CONCLUSIONS: We conclude that African Americans and Mexican
      Americans have greater postterm delivery rates than do Whites; however, commonly
      cited individual and community-level risk factors account for most of the
      disparity.

PMID- 11455992
TI  - Recent mammography use among African-American women.
AB  - OBJECTIVE: The incidence of breast cancer in Black women is lower, but their
      mortality rate is higher, compared to White women. Lower rates of mammography use
      among Black women in the past may have resulted in later diagnosis of breast
      cancer, leading to shorter survival periods and higher mortality rates. We
      assessed recent mammography use in a large national study, the Black Women's
      Health Study. DESIGN: In 1995, 27,632 US Black women aged 40-69 years completed
      mailed questionnaires, which included questions on mammography use. RESULTS:
      Seventy-three percent of women aged 40-49, and 82% of those aged 50-69, reported
      having had a mammogram within the previous three years. Use was greater among
      women with higher levels of education, and among those who had cystic breast
      disease or a mother or sister with breast cancer. CONCLUSIONS: The high rate of
      recent mammography use among participants in the Black Women's Health Study
      agrees with national data. If breast cancer mortality rates in Black women
      continue to exceed those in White women, despite the lower incidence among Black
      women, reasons other than differential mammography use must be sought.

PMID- 11455993
TI  - Preeclampsia associated with chronic hypertension among African-American and
      White women.
AB  - OBJECTIVE: To examine the racial differences in preeclampsia/eclampsia
      (preeclampsia) associated with chronic hypertension among African-American and
      White women. METHODS: Using hospital discharge summary records from the National
      Hospital Discharge Survey from 1988 to 1996, we conducted a case-control study to
      assess the risk of preeclampsia among women with chronic hypertension in two
      separate identical models: one for African-American and another for White women.
      Cases were pregnant women who developed preeclampsia. Controls were women without
      preeclampsia. The main exposure was chronic hypertension. Logistic regression was
      used to derive odds ratios (OR) and 95% confidence intervals (CI) and to assess
      interaction between hypertension and preeclampsia. Population attributable risk
      percent associated between chronic hypertension and preeclampsia was calculated
      for each ethnic group. RESULTS: Preeclampsia was more than eleven times likely
      among women with chronic hypertension compared to normotensive women for both
      African-American (OR = 12.4, 95% CI = 10.2-15.2) and White women (OR = 11.3, 95%
      CI = 9.7-13.2). Among African-American women, we found an interaction between
      chronic hypertension and region on preeclampsia. The effect of region magnified
      the risk of preeclampsia associated with chronic hypertension in general for
      African-American women, but the effect was lower for the Southern region (OR =
      8.9, 95% CI = 6.4-12.3). We also found that the point estimate of population
      attributable risk percent of preeclampsia attributable to chronic hypertension
      was significantly higher for African-American women (10.3, 95% CI = 8.6-12.5)
      compared to White women (5.3, 95% CI = 4.7-6.4). CONCLUSION: The more than eleven
      fold higher risk of preeclampsia among both African-American and White women with
      chronic hypertension compared to normotensive women underscores the potential
      risk of chronic hypertension for adverse pregnancy outcomes. Furthermore, the two
      fold higher population attributable risk percent of preeclampsia among African
      American compared to White women quantifies the burden of preeclampsia
      attributable to chronic hypertension, and indicates a greater opportunity for
      prevention.

PMID- 11455994
TI  - Minimal model analyses of beta cell secretion, insulin sensitivity and glucose
      effectiveness in glucose tolerant, non-diabetic first-degree relatives of
      Ghanaian patients with type 2 diabetes and healthy control subjects.
AB  - OBJECTIVE: We have examined the importance of positive family history of type 2
      diabetes on serum glucose, insulin sensitivity, and beta cell secretion in native
      West Africans (Ghanaians) who reside in their native country. RESEARCH AND
      METHODS: We evaluated the beta cell secretion, insulin secretion, insulin
      sensitivity (Si), and glucose effectiveness (Sg) in 42 healthy non-diabetic first
      degree relatives of Ghanaian patients with type 2 diabetes (26 females and 16
      males) and in 22 healthy control subjects without a family history of type 2
      diabetes (12 females and 10 males) living in Accra, Ghana, West Africa. A
      standard oral glucose tolerance test (OGTT) and a frequently sampled intravenous
      glucose tolerance (FSIGT) test were performed in each subject. Si and Sg were
      measured using Bergman's minimal model method. RESULTS: During oral glucose
      challenge, fasting and postprandial serum glucose levels were not significantly
      different between the relatives and healthy controls. Mean serum insulin and c
      peptide responses after oral glucose tolerance test at t = 60, 90 and 120 minutes
      (P<.05) were significantly greater in the relatives than in the healthy controls.
      During the FSIGT, the mean serum glucose responses did not differ. Mean total and
      acute first and second phases of serum insulin and c-peptide responses were
      greater in the relatives than in the healthy controls. We found that the Si
      tended to be lower in the relatives than in the controls, but the mean difference
      did not vary significantly between the two groups. In addition, the glucose
      effectiveness at basal insulin level (Sg) was not significantly different in the
      relatives and healthy controls. CONCLUSIONS: The present study demonstrates that
      hyperinsulinemia and a tendency to lower insulin sensitivity (insulin
      resistance), but not altered glucose effectiveness, are found in healthy non
      diabetic, first-degree relatives of Ghanaian patients with type 2 diabetes as
      compared to healthy subjects living in their native country. We conclude that
      genetic factors could play a significant role in the development of type 2
      diabetes in indigenous Ghanaians residing in their native country.

PMID- 11455995
TI  - The effect of enalapril on advanced diabetic nephropathy in African-American
      females.
AB  - This paper examines the effect of enalapril in African-American (AA) females with
      advanced type 2 diabetic nephropathy (DN)--the leading cause of end stage renal
      disease (ESRD) in this group. AA females followed in our university nephrology
      clinic with type 2 DN and a serum creatinine level (Cr) > or = 2.5 mg/dl were
      eligible. Historical controls who never received an ACE inhibitor were selected
      (matched for age and Cr) from a database of patients reaching ESRD between 1993
      and 1998, with a primary diagnosis of DN. Patients enrolled (N = 6) were started
      on enalapril at 5 mg per day with the dose titrated upward to a blood pressure
      (BP) goal of 140/90 mm Hg. The enalapril group tended to be older than controls
      (58.8 vs 51.5 years of age, P = ns) and had had their diabetes longer (18.5 vs
      13.2 years of age, P = ns). At baseline, there were no significant differences in
      blood pressure, blood, urea, nitrogen (BUN), Cr, or BMI between groups. One of
      the 6 treated with enalapril had the agent stopped due to hyperkalemia. Five of 6
      in the enalapril group reached ESRD, but there was no significant difference
      between the groups in the time it took to reach this stage (69.5 +/- 13.8 weeks
      vs 92.0 +/- 21.4 weeks, enalapril group vs control group, P = ns). In the
      enalapril patient who did not reach ESRD, the Cr level increased from 2.9 to 3.8
      mg/dl in approximately 3 years. From this small study, we conclude that, although
      enalapril is tolerated in AA females with advanced DN, the agent had no
      significant effect on renal survival.

PMID- 11455996
TI  - Physical activity and blood pressure responsiveness to the cold pressor test in
      normotensive young adult African-American males.
AB  - The aim of our study was to examine whether there is an association between blood
      pressure reactivity to the cold pressor test in African Americans who engaged in
      different levels of physical activity. We examined the systolic pressure,
      diastolic pressure, mean arterial blood pressure, heart rate, cardiac index,
      total peripheral resistance, and forearm blood flow during a two-minute cold
      pressor test in 15 aerobic, physically active and 15 physically inactive,
      normotensive young adult African-American males. Peak oxygen consumption varied
      as a function of physical activity, and was significantly higher in the
      physically active than in the physically inactive subjects (54.5 +/- 1.5 vs 36.8
      +/- 0.7 ml kg(-1) min(-1)) (P<.05). During the cold pressor test, consisting of
      immersing the foot in ice water, the change in cardiovascular responses were
      similar between the physically active and the physically inactive groups. These
      results suggest that regular physical activity may not contribute to an
      attenuated blood pressure response to behavioral stress of the cold pressor test
      in normotensive young adult African-American males.

PMID- 11455997
TI  - Achieving a healthy lifestyle among United States adults: a long way to go.
AB  - OBJECTIVE: The United States population has been advised to engage in various
      healthy lifestyle factors known to be associated with reduced morbidity and
      mortality from various chronic conditions. These include not smoking, adequate
      fruit and vegetable intake, adequate physical activity, and normal body weight.
      Little is known about the prevalence of United States adults who engage in all
      four of these behaviors, however. DESIGN: Cross-sectional analysis. SETTING: The
      third National Health and Nutrition Examination Survey (1988-1994). PARTICIPANTS:
      16,176 participants aged > or = 21 years. MAIN OUTCOME MEASURES: Percentage of
      participants engaging in four healthy lifestyle factors. RESULTS: Overall, 6.8%
      of the US population engaged in all four healthy lifestyle factors. Women were
      more likely than men (P = .001), and Whites and participants of "other race or
      ethnicity" were more likely than African Americans and Mexican Americans to
      engage in all four healthy lifestyle factors. A significant positive educational
      gradient was also evident (P for linear trend <.001). The highest percentages of
      participants engaging in all four lifestyle factors occurred among men (15.8%)
      and women (18.4%) of "other" race who had at least 13 years of education. The
      lowest percentages were observed for White men (1.1%) and African-American women
      (0.9%) with little education. CONCLUSIONS: The small proportion of US adults
      engaging in four healthy lifestyle factors demonstrates the enormity of the task
      that awaits the public health community in persuading Americans to adopt a
      multidimensional healthy lifestyle.

PMID- 11455998
TI  - Blood pressure levels in Xavante adults from the Pimentel Barbosa Indian
      Reservation, Mato Grosso, Brazil.
AB  - OBJECTIVE: To study blood pressure (BP) levels in the Xavante Indians of Central
      Brazil. METHODS: 93 subjects > or = 15 years old were included. Systolic (SBP)
      and diastolic (DBP) blood pressure readings were taken to the nearest mm Hg at
      Korotkoff phases 1 and 5 using a mercury sphygmomanometer. Height and weight
      measurements were taken, as well as general information on demographic, dietary,
      and social factors, including use of tobacco and alcohol. RESULTS: 5.3% of the
      adult men and 7.7% of the adult women (> or = 18 years old) were classified as
      hypertensive (SBP > or = 140 mm Hg and/or DBP > or = 90 mm Hg). No patients were
      classified as stage 3 hypertensive (SBP > or = 180 mm Hg or DBP > or = 110 mm
      Hg). Men had higher mean body weight and height than women. There was no major
      difference in mean BMI (body mass index) for men and women. SBP showed a positive
      and statistically significant correlation with age in both men (P = .056) and
      women (P = .040). Among men, DBP showed a negative correlation with height (P =
      .032). Among women, weight and BMI showed a positive correlation with DBP (P =
      .013 and P = .005, respectively). Diastolic pressure did not show statistically
      significant correlation with age for either sex (P>.05). CONCLUSION: The
      prevalence of hypertension has increased among the Xavante over the years, which
      is probably related to behavioral, social, and economic alterations deriving from
      increased interaction with Brazilian national society.

PMID- 11455999
TI  - Behavioral and demographic correlates of diabetes, hypertension and overweight
      among the Catawba Indian Nation.
AB  - OBJECTIVE: In 1998, the Catawba Diabetes and Health Survey (CDHS) was conducted
      among adult members of the Catawba Indian Nation living in the Carolinas to
      determine the prevalence of diabetes and other health conditions, and to assess
      the population's health-related behaviors. DESIGN: A population-based sample of
      adult members of the Catawba Indian Nation (N = 633) were surveyed by telephone
      or in person regarding health status and health-related behaviors. Logistic
      regression was used to determine demographic and behavioral correlates of
      diabetes, hypertension, and overweight among the Catawba. RESULTS: Age-adjusted
      prevalence rates of self-reported diabetes, hypertension and overweight were
      12.3%, 29.1%, and 63.8%, respectively. Older age was related to diabetes,
      hypertension, and overweight (P<.0001 each), and heavier weight status was
      related to diabetes (P = .026) and hypertension (P<.0001). Nearly 40% of the
      Catawba are physically inactive (29.5% men, 46.5% women). Physical inactivity was
      related to diabetes and hypertension among men only, and related to overweight
      among women only (P<.05 each). Current smoking was inversely related to
      overweight among men and women (P = .002). Dietary behavior was not associated
      with the health outcomes. CONCLUSION: Given the high rates of overweight and
      physical inactivity, reducing the rates of both may be very important for the
      health of the Catawba, considering their association with diabetes and
      hypertension.

PMID- 11456000
TI  - Development and reliability of a Telephone-Administered Perceived Racism Scale
      (TPRS): a tool for epidemiological use.
AB  - The conceptualization of perceived racism as a chronic stressor is relatively new
      to epidemiology. The Telephone-Administered Perceived Racism Scale (TPRS)
      captures the complexity of racism within five scales: Experience of Racism (by
      Blacks as a group and by the respondent), Emotional Responses, Behavioral
      Responses, Concern for Child(ren), and Past Experiences of Racism. The TPRS was
      developed for employed Black women. Exploratory factor analyses and tests of
      internal consistency were completed with 476 Black women, aged 36-53. Factor
      analyses on their responses to racism yielded five factors: passive emotions,
      active emotions, passive behaviors, internal active behaviors, and external
      active behaviors. Alpha reliability values ranged from 0.75 to 0.80 for the
      active and passive emotions subscales, from 0.59 to 0.69 for the passive
      behaviors subscale, and greater than 0.76 for both active behaviors subscales.
      Alpha reliabilities were 0.82, 0.90, 0.88, and 0.82 for Past Experiences, Concern
      for Child(ren), Experience of Racism--Personal, and Experience of Racism--Group,
      respectively. Another 30 Black women were queried for test-retest reliability,
      with values ranging from 0.61 to 0.82. The TPRS was found to be reliable and
      should serve as a useful epidemiological tool in the examination of the effects
      of perceived racism on Black women's health.

PMID- 11456001
TI  - Prevalence of self-reported illnesses in elderly Hispanic and non-Hispanic Whites
      in New Mexico.
AB  - OBJECTIVE: To report on the prevalences of self-reported illnesses from the New
      Mexico Elder Health Survey. DESIGN: Randomized community-based cross-sectional
      survey of elderly (> or = 65 years of age) Hispanics and non-Hispanic Whites.
      METHOD: Analysis of data from the 883 participants in the New Mexico Elder Health
      Survey. RESULTS: Complete data on 848 subjects were available for this analysis:
      Hispanic males, 212; Hispanic females, 189; non-Hispanic White males, 236; non
      Hispanic White females, 211. The mean age was 74 years (age range 65-98).
      Hispanics had fewer years of school and lower income. Hispanics reported a
      significantly (P<.05) higher prevalence of type 2 diabetes; leg ulcers/pressure
      sores; and Parkinson's Disease. Non-Hispanic Whites reported a significantly
      (P<.05) higher prevalence of asthma; circulatory problems; stomach (not ulcers),
      intestinal or gallbladder disease; urinary tract disorders (other than kidney
      disease); and cancer. Prevalence odds ratios and confidence intervals were
      calculated. Hispanic males reported a higher prevalence of type 2 diabetes (OR
      1.88, CI 1.10-3.26, P = .02), and lower prevalences of asthma (OR 0.43, CI 0.18
      0.93, P = .04); urinary tract disorders, other than kidney disease (OR 0.59, CI
      0.38-0.91, P = .01); and cancer (OR 0.31, CI 0.13-0.68, P = .005). Hispanic
      females reported a higher prevalence of diabetes (OR 3.01, CI 1.48-6.50, P =
      .003), and a lower prevalence of glaucoma (OR 0.48, CI 0.22-1.00, P = .05). These
      differences remained significant after adjustment for age, education, income, and
      language. CONCLUSION: There are significant differences in the prevalences of
      self-reported illnesses between Hispanic and non-Hispanic White elderly.

PMID- 11456002
TI  - Trends in births to parents of two different races in the United States: 1971
      1995.
AB  - PURPOSE: In 1997, the Office of Management and Budget (OMB) introduced revised
      standards for classification of federal data on race. The new standards include
      the option to report more than one race. Reasons for the new standards include a
      change over time in childbearing patterns by race. OBJECTIVE: To better
      understand how the new standards could impact different racial groups, we
      examined trends in interracial births in the United States from 1971-1995.
      DESIGN: Birth certificate data were used to analyze over 36,000,000 US births
      from 1971-1995. Race of mother and race of father were divided into four
      categories (Black, White, American Indian, and Asian or Pacific-Islander), and
      four Asian or Pacific-Islander subcategories (Chinese, Japanese, Hawaiian,
      Filipino). The national percent of interracial births was calculated by race of
      parents for five-year intervals. RESULTS: The percent of interracial births in
      the United States more than tripled from the 1971-1975 period to the 1991-1995
      period, but remained relatively small overall (3.9% in 1991-95). The percent of
      interracial births increased most dramatically among Black (from 0.8% to 4.0%)
      and White (0.8% to 2.6%) mothers, but these births were much more common among
      American Indian and Asian or Pacific-Islander (47% and 22% in 1991-1995,
      respectively) mothers. Nearly half (45%) of all interracial births occurred to
      White-Black parents, followed by White-Asian or Pacific-Islander parents (33%).
      CONCLUSION: Future statistical reporting of demographic and health
      characteristics by race of American Indian and Asian or Pacific-Islander
      populations could be impacted the most by the new OMB standards. For Whites and
      Blacks, the impact of multiracial reporting will be smaller, but is likely to
      increase.

PMID- 11456003
TI  - Efficacy of racism-specific coping styles as predictors of cardiovascular
      functioning.
AB  - OBJECTIVE: This study examined the relationship between racism-specific coping
      strategies and cardiovascular responses to an ethnically relevant speaking task.
      METHODS: Fifty-seven African-American females participated in a speaking task
      during which they discussed their experiences with inter-ethnic group racism.
      Blood pressure and heart rate responses were measured during a pre-speech,
      speech, and recovery period. Racism-specific coping strategies were assessed with
      both the Perceived Racism Scale (PRS) and the Ways of Coping Scale-Revised (WCS
      R). RESULTS: Multivariate regression analyses indicated that racism-specific
      coping strategies assessed via the PRS and WCS-R predicted blood pressure and
      heart rate changes. Passive coping strategies were generally associated with
      greater changes in systolic blood pressure, diastolic blood pressure, and heart
      rate during the pre-speech and speech periods, and with incomplete diastolic
      blood pressure recovery and heart rate recovery. Unexpectedly, the use of more
      active roping strategies was also associated with greater changes in diastolic
      blood pressure, and with incomplete heart rate recovery. CONCLUSION: This study
      provides preliminary empirical evidence that racism-specific coping styles may
      contribute to blood pressure and heart rate variability in African-American
      females.

PMID- 11456004
TI  - Community-based tobacco control program: the Mamre study, a demonstration
      project.
AB  - OBJECTIVES: To assess the feasibility of a 5-year community-based tobacco control
      program in the community of Mamre in South Africa, while measuring the smoking
      and quitting rates at the beginning and end of this demonstration project.
      METHODS: A tobacco intervention program was developed at low cost in
      collaboration with the community, and involved a wide range of activities
      targeting people of all ages, especially those at risk for cardiovascular
      disease. Community members were trained to deliver smoking cessation programs and
      specific advice to smokers. Cross-sectional surveys were conducted in 1989 in a
      random sample of 1238 people, aged 15 years and older, prior to the 5-year
      demonstration project, and again in 1996 among 974 people at the end of the
      project. Demographic data and smoking and quitting patterns were collected by
      interviewer-administered questionnaires. Trained field workers used standardized
      procedures for recording blood pressure, height, and weight. RESULTS: The
      community participated with enthusiasm in the activities surrounding smoking
      cessation and the annual World No Smoking Day. The smoking rate decreased
      significantly between the two surveys (OR 1996/1989 = 0.82; 95% CI of 0.69-0.99),
      and the quitting rate increased significantly during the 5-year intervention
      period compared to the 5 years prior to the baseline survey (OR 1996/1989 = 0.74;
      95% CI of 0.57-0.98). Men who participated in the program but continued to use
      tobacco in 1996 smoked more cigarettes than those who smoked in 1989. People who
      quit during the intervention period tended to be older, hypertensive, and obese;
      they consumed no alcohol, and noticed the health warnings posted in the community
      if they were older and had 10 or more years of education. CONCLUSIONS: A low-cost
      community-based tobacco control program was successfully implemented in the Mamre
      community. The program was received enthusiastically, built tobacco cessation
      skills, and significantly reduced the community's smoking rate compared to that
      before the demonstration project.

PMID- 11456005
TI  - Rates of change in measures of body size vary by ethnicity and gender.
AB  - Obesity, a major risk factor for a variety of diseases, is more common in Blacks
      than in Whites. In the current study, a cohort of young Blacks and Whites was
      followed longitudinally to determine rates of change in body mass index (BMI) and
      subscapular and triceps skinfold thickness from the ages of 5 to 25 years. A
      significant difference in the rate of change of BMI (P<.0001) between Blacks and
      Whites was observed with Blacks gaining at a faster rate. The rate of increase of
      subscapular (P<.0001) and triceps fat (P<.0001) was significantly higher in the
      girls than in the boys. We also examined for differences by household income and
      maternal education level. Children from poorer families had more fat (P<.01 for
      all three outcomes), whereas education level was not related to the amount of
      body fat. Differences in the prevalence of obesity between Blacks and Whites and
      between males and females that manifest during adulthood appear to begin in
      childhood. The results re-emphasize the important need for early intervention in
      weight control measures.

PMID- 11456006
TI  - Cocaine use and hypertension are major risk factors for intracerebral hemorrhage
      in young African Americans.
AB  - OBJECTIVE: To determine the risk factors for intracerebral hemorrhage (ICH) in
      African Americans aged 18 to 45 years. African Americans are at a higher risk for
      ICH than Whites, particularly in the younger age groups. However, few data are
      available regarding the factors that contribute to the high risk of ICH among
      younger African Americans. DESIGN: A case-control study. SETTINGS: A university
      affiliated public hospital. PARTICIPANTS: One hundred and twenty-two African
      American patients admitted with non-traumatic ICH to Grady Memorial Hospital
      (Atlanta, Ga.) and 366 age- and sex matched African-American controls selected
      from a nationally representative sample of the civilian, non-institutionalized US
      population. MAIN OUTCOME MEASURE: Association between ICH and various demographic
      and clinical factors determined by stepwise logistic regression. RESULTS: Cocaine
      use (OR 6.1, 95% CI 3.3-11.8), hypertension (OR 5.2, 95% CI 3.2-8.7) and alcohol
      use (OR 1.9, 95% CI 1.1-3.3) were independently associated with increased risk
      for ICH. CONCLUSIONS: Cocaine use, hypertension and alcohol use contributed to
      the high risk of ICH observed in younger African Americans. Primary preventive
      strategies are required to reduce the high frequency of modifiable risk factors
      predisposing younger African Americans to ICH.

PMID- 11456007
TI  - Guinea worm (Dracunculus medinensis) eradication: a pilot study conducted at the
      Ohaukwu Local Government Areas, Ebonyi State, Nigeria, West Africa.
AB  - The incidence and the prevalence of Guinea worm disease, a major cause of
      disability and a frequent cause of serious permanent deformity, were both
      drastically reduced in Ohaukwu Local Government Communities, with the provision
      (through bore holes) of a safer form of drinking water. Since 1986, the Carter
      Center program has been working to eradicate Guinea worm. The bore holes were dug
      through the Wasatan Project, a Japanese-funded grant awarded to the Enugu State
      Ministry of Health to help provide safer drinking water in the local communities.
      Bore holes were dug in several communities in Ohaukwu Local Government Areas
      between January 1991 and June 1991. The number of Guinea worm cases in the
      selected communities was ascertained and recorded by health workers. There was
      more than a 90% reduction in the number of Guinea worm (Dracunculus medinensis)
      cases after one year. Data collection began in June 1991, shortly after the
      completion of bore holes in the selected communities. By December 1998, when one
      of the villages was spot checked for Guinea worm infection, no active case was
      found. There is a need for post evaluation of all the villages studied to
      determine the current prevalence of Guinea worm disease.

PMID- 11456008
TI  - Racial differences in low-density lipoprotein particle size in families at high
      risk for premature coronary heart disease.
AB  - OBJECTIVE: Although small, dense low-density lipoprotein (LDL) has been
      implicated in atherogenesis and coronary heart disease (CHD) events, little is
      known about possible racial differences in LDL particle size. This study was
      designed to examine racial differences in the prevalence of small, dense LDL
      among 159 African-American and 477 White siblings of persons with premature (<60
      years of age) CHD. METHODS AND RESULTS: This study examined fasting levels of
      total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol,
      apolipoprotein B (ApoB), apolipoprotein A-1, and triglycerides, as well as
      factors known to be associated with small, dense LDL, including age, sex,
      obesity, hypertension, and diabetes. Relative LDL particle size was defined by
      the LDL cholesterol to ApoB ratio. Direct measurement of LDL particle size was
      obtained by proton NMR spectroscopy in a subset of 64 siblings. Despite similar
      levels of total and LDL cholesterol, White siblings were more likely to have low
      LDL cholesterol to ApoB ratios, indicative of atherogenic small, dense LDL,
      compared with African-American siblings. Multiple logistic regression analysis
      predicting the presence of LDL cholesterol/ApoB < or = 1.0 demonstrated that race
      (P = .009), triglyceride level (P = .0001), and diabetes (P = .02) were
      independent predictors, controlling for age and all other variables. Direct
      measurement of LDL particle size by NMR spectroscopy supported these findings.
      CONCLUSION: These findings provide the first known evidence that White
      individuals from a population at high risk for premature CHD have a greater
      probability of having a preponderance of small, dense LDL particles than do
      African Americans, independent of triglyceride levels, and despite comparable
      levels of total and LDL cholesterol.

PMID- 11456009
TI  - Interactions between ocular surface fluid and cornea related to contact lenses.
AB  - PURPOSE: To improve the quantification of damage to the ocular surface,
      metabolite levels, electrolyte concentrations, and enzyme activities were assayed
      in corneal epithelium, stroma and tears. METHODS: In rabbits, rinsing or contact
      lenses were used to induce microtrauma. For more severe trauma, experimental
      injuries were induced with 1 N NaOH. Human accidents included epithelial lesions
      and mild chemical burns. Enzymatic test systems and electron dispersive X-ray
      analyses (EDXA) were employed. Corneal hydration was assessed by wet and dry
      weights. Interleukins were analysed with ELISA. RESULTS: In contrast to normal
      eyes, in ocular surface trauma the interaction between tear fluid and cornea
      played an important part. After wearing contact lenses or rinsing, glucose and
      lactate levels in the cornea and in tears increased, and ATP and glycogen in the
      cornea decreased. After epithelial lesions, N-acetylglucose aminidase (NAcGA,
      E.C.3.2.1.50) was released into the tears. Epithelial defects alone and--much
      more--rinsing the denuded stromal surface produced an increase of lactate and
      glucose in tears and a dramatic fall in Na, Cl, and S levels in the stroma.
      Rinsing with phosphate induced corneal calcification. IL-1 and IL-6 were
      increased in human corneal buttons from patients with trauma and inflammation.
      CONCLUSIONS: Biochemical analyses may be useful to quantify trauma to the ocular
      surface.

PMID- 11456010
TI  - Corneal topographical study of the effect of lacrimal punctum occlusion on
      corneal surface regularity in dry eye patients.
AB  - PURPOSE: To compare topographic indices of surface regularity in dry eye patients
      and in normal subjects (controls) and to investigate the short-term effect of
      lacrimal punctal plugs on these indices in dry eye patients. METHODS: The surface
      regularity index (SRI) and surface asymmetry index (SAI) of the TMS-2 corneal
      topographic modelling system were used to evaluate corneal surface regularity in
      20 eyes of 10 dry eye patients before and after the insertion of Herrick silicon
      lacrimal plugs (Lacrimedics, Rialto, CA, USA) and in 24 eyes of 12 normal
      subjects as controls. RESULTS: SRI and SAI were significantly lower in controls
      than dry eye patients (p=0.00). Median SRI was 1.72 in dry eye patients before
      punctal occlusion and 0.525 in the control group. Median SAI was 1.305 in dry eye
      patients and 0.240 in controls. After lacrimal punctal occlusion, Schirmer test
      results and fluorescein breakup time increased in nine patients and remained the
      same in one patient. After occlusion, the SRI decreased in 9 eyes, and increased
      in 11 (p=0.970); SAI decreased in 13 eyes and increased in 7 (p=0.135).
      CONCLUSIONS: No significant change in topographic indices of corneal surface
      irregularity could be detected in severe dry eye patients with lacrimal punctal
      plugs in the short-term follow-up.

PMID- 11456011
TI  - Comparison of lodoxamide 0.1% ophthalmic solution and levocabastine 0.05%
      ophthalmic suspension in vernal keratoconjunctivitis.
AB  - PURPOSE: To compare the clinical efficacy and safety of lodoxamide 0.1%
      ophthalmic solution with levocabastine 0.05% ophthalmic suspension, each given
      four times daily (QID) for three months to patients with vernal
      keratoconjunctivitis (VKC). METHODS: The study was conducted multinationally
      according to a triple-masked parallel design in 95 VKC patients, with assessments
      at baseline then monthly during the three months of treatment. The primary
      efficacy variables were a Physician's Clinical Judgement Scale and a Patient's
      Overall Judgement Scale of improvements from baseline. Signs and symptoms of VKC
      were also assessed. RESULTS: Both primary efficacy variables showed significantly
      greater overall improvement of VKC from baseline with lodoxamide than
      levocabastine. The superiority of lodoxamide was demonstrated by the Physician's
      Clinical Judgement Scale at months 2 and 3, with a trend, at month 1, and by the
      Patient's Overall Judgement Scale at months 1, 2 and 3. All signs and symptoms of
      VKC improved significantly from baseline at all time points, regardless of
      treatment (p<0.001). However, relative to levocabastine, conjunctival discharge,
      photophobia and lacrimation were significantly reduced by lodoxamide at months 1,
      2 and 3, itching at months 2 and 3, and bulbar conjunctiva at month 3. The
      temporal improvement of superior tarsal papillae did not differ significantly
      between treatments. Both were well tolerated. CONCLUSIONS: Lodoxamide 0.1% and
      levocabastine 0.05% eye drops, instilled four times daily for three months, were
      effective, safe and well tolerated by patients with VKC, but lodoxamide was
      significantly superior to levocabastine.

PMID- 11456012
TI  - Comparative efficacy of beta-irradiation and mitomycin-C in primary and recurrent
      pterygium.
AB  - PURPOSE: To determine the efficacy and safety of mitomycin-C as adjunctive
      treatment and to compare this drug with beta irradiation with strontium-90 after
      surgical excision of primary and recurrent pterygia. MATERIALS AND METHODS: The
      study group consisted of 193 patients with primary and recurrent pterygia who
      underwent surgical excision with the bare sclera technique. They were divided
      into two groups according to the type of adjunctive treatment. In group I, 130
      patients (141 eyes, 67.8%) were treated with beta irradiation with Sr-90 doses of
      1000-7000 cGy. In group II 63 patients (67 eyes, 32.2%) received topical
      mitomycin-C at a concentration of 0.02% four times daily for one week
      postoperatively. Recurrence rates, complications and efficacy of these treatments
      were compared with the chi-square of Fisher's exact test. RESULTS: The recurrence
      rates were 6.4% in group I after a mean postoperative follow-up of 89 months and
      17.9% in group II after a mean follow-up of 14.9 months. Recurrence, rates and
      complications were higher in group II and the difference was significant (p<0.05,
      p<0.001). Life-table analysis showed a success rate of 93.6% for Sr-90 and 81.9%
      for the mitomycin-C, the difference being significant (p<0.005). CONCLUSIONS:
      Beta irradiation with Sr-90 after surgical excision was more effective than
      topical mitomycin-C in patients with primary and recurrent pterygium in terms of
      recurrence rates, and safer in terms of complications.

PMID- 11456013
TI  - Older age as risk factor for deviation from emmetropia in pseudophakia.
AB  - PURPOSE: To find risk factors for deviation from emmetropia after cataract
      surgery in clinical practice. METHODS: We evaluated the refractive outcome in 106
      patients who had underone phacoemulsification and in-the-bag IOL placement 115 +/
      10 days after surgery. Postoperative optical correction and refractive error
      (diopters of spherical equivalent--ED) were related to age and sex, pre-operative
      axial length and keratometric diopter power, and operative incision technique.
      RESULTS: Emmetropia was achieved in 15% of cases; 65% of eyes needed a myopic
      correction, averaging = 0.46 +/- 0.91 ED. The refractive error was 0.74 +/- 0.61
      ED (< or = 1 ED in 77% of cases, < or = 2 ED in 97%). Both optical correction and
      refractive error were correlated to older age at the time of surgery (p=0.002 and
      p=0.001, respectively). Astigmatism appeared greater in clear-cornea incision
      than in limbar incision cases (p=0.05). CONCLUSIONS: The higher refractive error
      in patients aged over 73 years suggests that age may be a risk factor for
      deviation from emmetropia after cataract surgery.

PMID- 11456014
TI  - Nerve fiber layer assessment with scanning laser polarimetry in glaucoma patients
      and glaucoma suspects.
AB  - PURPOSE: To investigate whether scanning laser polarimeter can differentiate
      glaucoma and suspected glaucoma patients from normals. METHODS: Polarimetric
      measurements were obtained using the nerve fiber analyzer (NFA)-I from 80 eyes of
      patients with glaucoma with mostly moderate glaucomatous optic nerve damage (37
      eyes with primary open angle glaucoma, 21 with normal tension glaucoma, 17 with
      pseudoexfoliative glaucoma, 3 with angle closure glaucoma, and 2 with juvenile
      glaucoma), 53 eyes of patients suspected of glaucoma based on disc appearance,
      and from age-matched healthy volunteers as control groups. Ratios
      (superior/nasal, inferior/nasal, superior/inferior) were used for assessing nerve
      fiber layer (NFL) thickness. Student's t-test and linear regression analysis were
      used for statistical analysis. RESULTS: Both the glaucoma patients and glaucoma
      suspects had significantly lower NFL ratios (mean S/N 2.34 +/- 0.47, I/N 2.46 +/-
      0.52, S/I 0.94 +/- 0.18) than the control groups (respectively 2.88 +/- 0.48,
      2.88 +/- 0.48, 1.00 +/- 0.13) (p<0.05). There was an ample overlap between the
      patient groups and the normals. The superior and inferior NFL ratios in glaucoma
      patients gradually decreased as the mean defect in visual field increased (linear
      regression analysis, p<0.05). CONCLUSIONS: The NFL of glaucomatous eyes and eyes
      suspected of glaucoma based on disc appearance was significantly less thick than
      normals. NFA-I detects pathological abnormalities in some patients with
      glaucomatous optic nerve damage and normal visual fields as measured by
      conventional achromatic computerized perimetry. NFA-I, however, is unable to
      distinguish these patients from normals, at least using these parameters, because
      of the considerable overlap.

PMID- 11456015
TI  - A quantitative in vivo study of retinal thickness before and after laser
      treatment for macular edema due to retinal vein occlusion.
AB  - PURPOSE: To evaluate quantitatively the effect of grid laser photocoagulation in
      macular edema due to central and branch retinal vein occlusion, using the retinal
      thickness analyzer. METHODS: Five patients with cystoid and non-cystoid macular
      edema were studied before and after argon grid laser treatment. All were examined
      clinically, with fluorescein angiography, and measurement of retinal thickness.
      Macular thickness was correlated to visual acuity measured on the ETDRS chart.
      RESULTS: Laser-slit images obtained with the retinal thickness analyzer in
      patients with macular edema disclosed discrete intraretinal changes after
      photocoagulation. Biomicroscopy and fluorescein angiography were insensitive to
      these small changes in the retinal thickness. No patient had any change in visual
      acuity after three months, but the retinal thickness was greater at this
      interval. The retinal thickening may be explained by a postoperative inflammatory
      response or by altered retinal blood flow or, in two of the eyes, by the effect
      of combined peripheral photocoagulation. CONCLUSIONS: The retinal thickness
      analyzer offers a refined tool for the diagnosis of subclinical changes of
      macular edema in retinal vein occlusion and is therefore also useful for
      assessing the effects of treatment.

PMID- 11456016
TI  - Color Doppler imaging of untreated and irradiated choroidal melanomas.
AB  - PURPOSE: We examined untreated and irradiated choroidal melanomas with color
      Doppler imaging (CDI), a noninvasive method providing quantitative measures of
      blood flow, to determine if the tumor vessel damage associated with irradiation
      can be detected using this technology. METHODS: CDI was performed on 122
      untreated and 76 previously irradiated tumors using a Q2000 color Doppler
      ultrasound unit. Spectral analysis was performed on all detectable vascular
      regions within the tumor to obtain estimates of the peak systolic and end
      diastolic flow velocities and resistive index ((syst-diast)/syst). RESULTS:
      Vessels were detected in 93% of the untreated tumors and in 63% of the treated
      tumors (p<0.001, X2), and the median number of vascular regions found was higher
      among untreated tumors (3 vs 1, p=0.001, Wilcoxon Rank Sum). The effect of
      treatment status on the detection of tumor vessels was significant (p=0.039),
      controlling for age, sex, largest tumor pretreatment diameter, and tumor height
      at CDI in a logistic regression model. Mean resistive index was lower in the
      untreated tumors (0.53 vs 0.58, p=0.0050), controlling for tumor height and other
      covariates in an analysis of variance. CONCLUSIONS: On examination with CDI,
      irradiated tumors had fewer detectable vascular regions and greater resistance to
      flow than untreated tumors, a pattern consistent with known radiation effects.

PMID- 11456017
TI  - Subretinal fluid ferning test in rhegmatogenous retinal detachment.
AB  - PURPOSE: The ferning test involves a process of crystallization achieved simply
      by removing water and is feasible for all ocular fluids. The ferning test of
      subretinal fluid (SRF) from patients with rhegmatogenous retinal detachment (RRD)
      reveals three different patterns: type 1 showing thin crystals, type 2 with
      larger crystals and type 3 with small, curvilinear structures with no tree-like
      appearance. The present study was designed to determine whether the SRF ferning
      test is correlated with the clinical features and the surgical outcome of RRD.
      METHODS: A series of 65 consecutive patients with RRD at the first onset were
      considered. Particular attention was paid to duration, extension, and surgical
      outcome of RRD. SRF samples were collected during scleral buckling surgery. The
      fluid was dropped onto the slide of a light microscope, left to dry, and examined
      under the microscope. RESULTS: There was a significant difference between SRF
      ferning types 1 and 2 as regards, duration and extension (both p < 0.001). There
      was also a significant difference between SRF ferning types 2 and 3 as regards
      duration (p<0.001), extension (p<0.001), and surgical outcome (p<0.05).
      CONCLUSIONS: The ferning test of SRF is quick and simple and can be regarded as a
      useful tool for obtaining information about clinical features, such as duration
      or extension of first, onset in uncomplicated cases of RRD especially for
      purposes of forensic medicine.

PMID- 11456018
TI  - Methicillin resistance of bacteria isolated from vitreous fluid from patients
      undergoing vitrectomy.
AB  - PURPOSE: The aim of this study was to compare the resistance patterns of bacteria
      in vitreous fluid from patients undergoing vitrectomy for diagnostic reasons,
      with bacteria of other nosocomial infections. METHODS: Vitreous fluid samples
      (n=144) were obtained from 133 patients undergoing vitrectomy for
      endophthalmitis, and 11 for uveitis as suspected endophthalmitis. They were Gram
      stained and cultured. Antibiotic susceptibility tests were run on all isolates.
      RESULTS: Gram stains were positive in 45/144 cases (31%), among which 38/45 (84%)
      were confirmed by a positive culture. Cultures were positive in 74/144 patients
      (51%) with mainly coagulase-negative staphylococci (n = 44) and Staphylococcus
      aureus (n = 13). In 133 patients endophthalmitis occurred after lens implantation
      (80 cases) and in 53 cases there was another origin (e.g. corneal
      transplantation, endogenous). In 26/80 post-lens implantation infections, culture
      remained negative; 32 infections occurred with coagulase-negative staphylococci,
      10 with Staphylococcus aureus, 9 with streptococci and 3 with gram-negative
      bacteria. For endophthalmitis, ophthalmologists in our institution give an
      intraocular injection of vanccmycin and ceftazidim after vitrectomy. Among the 44
      isolates of coagulase-negative staphylococci, 12 (27%) were resistant to
      methicillin. This is in contrast to other hospital-related coagulase-negative
      staphylococcus infections in general, and the resistance rate is 75% in our
      hospital. Only 2/13 Staphylococcus aureus isolates were methicillin-resistant.
      CONCLUSIONS: We conclude that isolates of coagulase-negative staphylococci from
      vitreous fluid are less resistant to methicillin than those isolated in other
      nosocomial infections.

PMID- 11456019
TI  - Recurrences of retinal detachment after vitreoretinal surgery, and surgical
      approach.
AB  - PURPOSE: To investigate the causes and management of recurrences of complicated
      retinal detachment after vitreoretinal surgery. METHODS: Vitreoretinal surgery
      was performed in 61 patients with complicated retinal detachment who were
      followed up for 4-24 (mean 7) months. Liquid perfluorocarbon (PFC) was used in
      all 61, silicone oil in 40 and perfluoropropane (C3F8) in 18 patients. RESULTS:
      Retinal attachment was achieved in 58 patients (95%) during the first operation.
      Due to the recurrence of detachment 17 patients (29%) had to be operated for a
      second, 7 (12%) a third and 4 (7%) a fourth time. Anterior and posterior
      proliferative vitreoretinopathy, missed tear, retinal incarceration, subretinal
      membrane and perisilicone proliferation were the factors causing redetachment.
      CONCLUSIONS: The best anatomical and functional results are obtained by
      dissection of the anterior membranes. In order to properly remove the retinal
      periphery the crystalline or intraocular lens should be removed. Comparison of
      our results with others indicates that anatomical success depends, to a certain
      extent, on doing only one, radical operation on the pathology that leads to
      recurrence.

PMID- 11456020
TI  - Palbebral anthrax.
AB  - PURPOSE: Anthrax is a rare infection transmitted to humans from animals or animal
      products. In cutaneous anthrax it may produce lesions of the eyelids which can
      lead to cicatricial ectropion. METHODS: We examined three women and five men with
      anthrax of the eyelids. Intravenous penicillin G was used alone as therapy.
      RESULTS: All patients presented with a localized itchy erythematous papule of the
      eyelid. A necrotising ulcer formed in each case, resulting in black eschar. The
      lesions resolved, with only mild cicatrization of the eyelid in all the patients.
      CONCLUSIONS: Anthrax is primarily an infectious disease of domestic animals but
      it is also seen in humans. Eyelids are rarely affected but cutaneous anthrax
      should be considered in any patient with a painless ulcer or black eschar who has
      a history of exposure to animals.

PMID- 11456021
TI  - Susac syndrome: a vasospastic disorder?
AB  - PURPOSE: The Susac syndrome is a microangiopathy that leads to visual symptoms,
      hearing loss and neurological symptoms. CASE REPORT: We report on a young woman
      suffering from this syndrome who also presented the following signs and symptoms
      typical of a vasospastic syndrome; 1) a history of cold hands, low blood pressure
      and migraine; 2) a typical alteration of conjunctival vessels; 3) prolonged flow
      arrest time after cooling in nailfold capillaromicroscopy; 4) increased
      resistivity in the orbital vessels measured by color Doppler imaging; and 5) an
      increased plasma level of endothelin-1. CONCLUSIONS: We postulate that the Susac
      syndrome is a manifestation of the vasospastic syndrome.

PMID- 11456022
TI  - Necrotising fasciitis of the orbit: early recognition and treatment a key to
      success.
AB  - PURPOSE: To report a case of necrotising fasciitis which was managed successfully
      with timely intervention. CASE REPORT: A 77-year-old lady diagnosed as having
      narcotizing fasciitis of the orbit based on the clinical picture and microbiology
      report is presented. Early recognition of the condition followed by timely
      surgical intervention in the form of surgical debridement and subsequent
      exenteration led to a favorable prognosis. DISCUSSION: Necrotising fasciitis is a
      fulminant synergistic infection. It spreads along facial planes causing necrosis
      of the overlying skin. Management of this condition includes both medical
      treatment and surgical debridement. Early intervention is of vital importance to
      save the patient's life as septicemia often leads to death within 24-96 hours.
      CONCLUSIONS: Early recognition and treatment are the key to successful management
      of cases with necrotising fasciitis of the orbit.

PMID- 11456023
TI  - Multilayer amniotic membrane transplantation in severe ocular graft versus host
      disease.
AB  - PURPOSE: To clarify the usefulness of multilayer amniotic membrane
      transplantation in an unusual case of calcareous corneal degeneration in a
      patient with graft-versus-host disease. METHODS: A 20-year-old Caucasian woman
      had bilateral calcareous corneal degeneration of one year of evolution, secondary
      to graft-versus-host disease. Treatment for both eyes with topical steroids and
      antibiotic ointment was not successful. Right eye had a spontaneous corneal
      perforation, and a three-layer circle amniotic membrane graft was applied to the
      whole cornea. RESULTS: During a follow-up period of 20 months we observed
      stability of the corneal epithelium and stroma. The amniotic membrane-covered
      area showed rapid epithelization, reduced inflammation and suppressed fibrosis
      formation. CONCLUSIONS: Multilayer amniotic membrane transplantation may be
      considered an alterantive for reconstructing the ocular surface in a patient with
      severe dry eyes and calcareous corneal degeneration, even with little
      perforation.

PMID- 11456024
TI  - Aerosol keratopathy: a revised MacLean classification.
AB  - Case report. Chemical keratopathy has been linked to many household aerosols. We
      present a dramatic case of aerosol keratopathy. The finding of an unexplained
      epithelial or superficial stromal keratopathy must alert the physician to inquire
      about the use of household aerosols near the patient's face. We also propose a
      revised classification system based on the work of MacLean.

PMID- 11456025
TI  - Delayed-onset postoperative endophthalmitis caused by Hafnia alvei.
AB  - PURPOSE: To identify Hafnia alvei as an etiological factor of delayed-onset
      endophthalmitis. CASE REPORT: A 68-year-old woman had uneventful cataract
      extraction by phacoemulsification with foldable posterior chamber intraocular
      lens implantation under topical anesthesia in the left eye. Four weeks later, the
      patient presented anterior uveitis treated by topical corticosteroids. Seven
      weeks later a posterior uveitis with retinal vasculitis appeared. The patient was
      treated by systemic and intravitreal corticosteroids without result. Due to the
      poor course pars plana vitrectomy was done, and a vitreous sample was taken.
      Microbiologic examination disclosed Hafnia alvei, gram-negative bacteria rarely
      isolated from human specimens. CONCLUSIONS: Hafnia alvei should be considered in
      the etiology of delayed-onset endophthalmitis.

PMID- 11456026
TI  - Sympathetic ophthalmia after complicated cataract surgery and intraocular lens
      implantation.
AB  - PURPOSE: To report a case of sympathetic ophthalmia (SO) associated with cataract
      surgery and intraocular lens (IOL) implantation. METHODS: Case report. RESULTS: A
      50-year-old man developed SO two months after complicated cataract surgery and
      IOL implantation. Adequate and prompt use of immunosuppressive medications and
      removal of the IOL by pars plana vitrectomy techniques resulted in control of the
      uveitis with significant visual improvement. CONCLUSIONS: Sympathetic ophthalmia
      should be included as one of the devastating complications of IOL insertion. A
      high index of suspicion must be maintained whenever inflammation occurs in the
      fellow eye of an eye that has undergone intraocular surgery.

PMID- 11456027
TI  - Central retinal vein occlusion and sudden deafness: a possible common
      pathogenesis.
AB  - CASE REPORT: A 31-year-old woman complained of blurred vision in the right eye
      due to a well-perfused central retinal vein occlusion (CRVO) and two months
      later, of sudden deafness (SD) in her right ear. Her visual acuity and hearing
      recovered almost completely within a few months. Medical evaluation disclosed the
      combination of slight coagulation abnormalities (moderate decrease in protein S,
      slightly elevated lipoprotein (a)), and elevated fibrinogen, with plasma
      hyperviscosity. DISCUSSION: The occurrence of CRVO then SD suggests that the same
      underlying conditions can be considered as risk factors for both diseases and
      shows up some similarities in the pathogenesis of these acute impairments of
      microvascular blood flow in the retina and the cochlea.

PMID- 11456028
TI  - Progressive outer retinal necrosis syndrome: successful treatment with a new
      combination of antiviral drugs.
AB  - PURPOSE: To describe a case of progressive outer retinal necrosis syndrome,
      successfully treated with a new combination of antiviral drugs. METHODS: The
      patient was treated with a combined therapy of antiviral drugs that includes:
      intravenous acyclovir 10 mg/kg, three intravitreal injections of foscarnet (1200
      microg) and a ganciclovir implant in the right eye. RESULTS: The progressive
      outer retinal necrosis appeared to response dramatically with the combination of
      antiviral agents used over a period of 2 weeks with a final visual acuity of
      20/80 at 3 months of follow up. CONCLUSIONS: Intravitreal foscarnet combined with
      i.v. acyclovir and ganciclovir implant may represent an effective alternative
      treatment for PORN.

PMID- 11456029
TI  - Optic nerve lesion following neuroborreliosis: a case report.
AB  - PURPOSE: Neuroborreliosis may cause various neuro-ophthalmological complications.
      We describe a case with a bilateral optic neuropathy. CASE REPORT: A 58-year-old
      female developed facial paresis six weeks after an insect bite. One week later
      she developed bilateral optic disc swelling with haemorrhages and nerve fibre
      bundle defects in the lower visual field of the left eye. In CSF and serum,
      raised IgM and IgG titres to Borrelia burgdorferi were found. Systemic antibiotic
      treatment led to improvement of the vision and facial paresis, but not all visual
      field defects resolved, probably due to ischemic lesions of the optic disc.
      DISCUSSION/CONCLUSIONS: In optic nerve lesions due to neuroborreliosis it is
      difficult to distinguish between inflammatory and ischemic lesions. This patient
      demonstrated features of an ischemic optic nerve lesion.

PMID- 11456030
TI  - Exudative retinal detachment in hemiretinal vein occlusion.

PMID- 11456031
TI  - Private health: has it a future?

PMID- 11456032
TI  - Adverse drug events as a cause of hospital admission in the elderly.
AB  - BACKGROUND: Previous studies of adverse drug events (ADE) as a cause of hospital
      admission in the elderly have often been limited in their ability to assess fully
      the impact and potential for prevention because they either did not include all
      categories of ADE and/or did not assess severity and preventability. AIMS: To
      assess the frequency, severity and preventability of ADE causing emergency
      medical admissions in the elderly. METHODS: Cross-sectional survey of 219
      patients aged 75 years and over who were consecutive unplanned admissions to
      acute medical units of the Royal Hobart Hospital in an 8-week period during
      August and September 1998. RESULTS: Seventy-three of 240 (30.4%) admissions may
      have been a result of ADE. Patients admitted because of ADE were taking more
      drugs than those admitted for other reasons. Most ADE were adverse drug reactions
      to a single (46%) or multiple drugs (25%). Non-compliance, omission or cessation
      of indicated treatment accounted collectively for 26% of admissions. Of all ADE
      admissions 53.4% were considered definitely preventable. The commonest causative
      drugs were cardiovascular drugs (48.4%), and the commonest manifestations were
      falls and postural hypotension (24.1%), heart failure (16.9%) and delirium
      (14.5%). ADE categories in which a high proportion of admissions was both severe
      and definitely preventable were non-compliance and omission of indicated
      treatment. CONCLUSIONS: Adverse drug events are a common preventable cause of
      unplanned medical admissions in the elderly. Non-compliance and omission of
      indicated treatment are causes of ADE-related admissions that are both
      preventable and frequently associated with severe ADE.

PMID- 11456033
TI  - Myasthenia gravis with thymoma is more common in the Maori and Pacific Island
      populations in New Zealand.
AB  - BACKGROUND: The association of myasthenia gravis (MG) with thymoma is well
      recognized. Our clinical impression has been that MG associated with thymoma may
      be more common in patients of Polynesian descent than in other races. AIM: To
      determine the influence of ethnicity on the association of MG with thymoma in our
      population. METHOD: Review of all cases of thymectomy performed at Greenlane
      Hospital in Auckland for the 20-year period from June 1978 to June 1998. RESULTS:
      There were 103 thymectomies performed in the study period. Fifty-five thymomas
      were identified, 15 in subjects of Maori or Pacific Island ethnicity and 40 in
      subjects of other races, predominantly Caucasian. Ten of 15 Maori or Pacific
      Island subjects with thymoma had MG (67%), compared with 15 of 40 subjects of
      other races (37.5%, P = 0.05). The mean age of Maori or Pacific Island subjects
      with thymoma and MG was 42.5 years, compared with 56.3 years in subjects from
      other races (P = 0.06). All five Maori and Pacific Island subjects with invasive
      thymoma had MG, whereas only four of 15 subjects (27%) from other races with
      invasive tumours had MG (P < 0.01). The overall incidence of thymoma and the
      proportion of thymomas that were invasive did not differ between the ethnic
      groups. CONCLUSIONS: Myasthenia gravis with thymoma occurs more frequently among
      Maori or Pacific Island people than in other racial groups in our population.
      This is due to an increase in the proportion of cases with thymoma who have MG in
      this group, while the overall frequency of cases of thymoma is similar between
      groups. MG with thymoma in the Maori or Pacific Island populations also presents
      at a younger age and is more often associated with tumour invasion.

PMID- 11456034
TI  - Plasma amino-terminal pro-brain natriuretic peptide levels in subjects presenting
      to the Emergency Department with suspected acute coronary syndrome: possible role
      in selecting patients for follow up?
AB  - BACKGROUND: Plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) level
      is a sensitive and specific indicator of cardiac dysfunction. AIM: To determine
      whether plasma NT-proBNP level is elevated at the time of presentation with acute
      coronary syndrome (ACS) and whether it may assist in the diagnosis of heart
      failure and myocardial ischaemia in the Emergency Department. METHODS: Plasma NT
      proBNP levels were measured prospectively in 201 unselected presentations to the
      Emergency Department with suspected ACS where cardiac injury markers were
      requested by clinicians as part of routine assessment. NT-proBNP levels were
      correlated with clinical, electrocardiogram (ECG), biochemical and radiological
      findings. RESULTS: Elevated NT-proBNP level detected heart failure with high
      sensitivity (95-96%). Among patients without heart failure, NT-proBNP levels were
      increased more frequently in patients with previously diagnosed ischaemic heart
      disease. Elevated NT-proBNP level predicted cardiomegaly and a cardiac cause of
      presentation. However, the NT-proBNP level was not associated with ECG or
      biochemical markers of myocardial ischaemia, and only one-third of patients with
      ACS showed an increase of 40% or more in NT-proBNP level at repeat measurement of
      cardiac injury markers 5 h after presentation. CONCLUSIONS: Although elevated NT
      proBNP level detected heart failure with high sensitivity, NT-proBNP level did
      not assist in the diagnosis of acute myocardial ischaemia. These findings
      indicate that the major determinant of elevated NT-proBNP level on presentation
      with suspected ACS was underlying cardiac dysfunction rather than acute
      myocardial ischaemia. This suggests that NT-proBNP measurement in patients with a
      suspected cardiac reason for presentation to the Emergency Department may
      identify a previously unrecognized group of patients without acute ischaemia who
      may nevertheless benefit from further investigation of cardiac function.

PMID- 11456035
TI  - Scleroderma in South Australia: epidemiological observations of possible
      pathogenic significance.
AB  - BACKGROUND: Scleroderma is an autoimmune disorder of unknown cause. Previous
      epidemiological studies have suggested some regional clustering and associations
      with occupations involving exposure to silica dusts and hydrocarbons. AIMS: To
      determine: (i) prevalence and incidence of scleroderma in South Australia (SA), a
      state with a stable population living in well-defined urban, rural and industrial
      regions, (ii) hospital separation rates, (iii) cumulative survival rates, (iv)
      gender and disease subclassification, (v) geographical residency and occupations,
      (vi) familial associations and (vii) age at onset versus age-specific incidence
      rate. METHODS: Creation of the South Australian Scleroderma Register (SASR) to
      identify demographics and clinical and serological features of all scleroderma
      patients resident in SA. RESULTS: Scleroderma occurs in South Australia with a
      point prevalence of 23 per 10(5) and an incidence of approximately 1/15th of
      this. However, this prevalence is high compared with other regional world
      studies. Scleroderma is predominantly a female disease, with most patients having
      the limited form of scleroderma characterized by the presence of the
      anticentromere antibody and a mean survival of 27.6 years. In contrast, diffuse
      scleroderma is a less benign disease occurring at an early age of onset and has a
      mean survival of 9.6 years. Scleroderma occurs throughout SA without regional
      localization. Weak associations are seen in males, but not females, with
      occupations involving possible environmental exposure to silica or hydrocarbons.
      Scleroderma rarely occurs in families. CONCLUSION: No strong genetic or
      environmental influences were found to account for the relatively common
      occurrence of scleroderma in SA. The age at onset versus age-specific incidence
      curve suggests that scleroderma can be considered as a stochastic illness
      involving a number of random events occurring in a predisposed population. These
      random events may involve mutations of pivotal somatic genes.

PMID- 11456036
TI  - Factors influencing the uptake of technologies to minimize perioperative
      allogeneic blood transfusion: an interview study of national and institutional
      stakeholders.
AB  - BACKGROUND: Alternatives to allogeneic blood transfusion exist and are being used
      to varying extents in Australian hospitals. Evidence on effectiveness and cost
      effectiveness is generally inconclusive and provides a suboptimal basis for
      policy development. AIM: To describe the influences on uptake of transfusion
      technologies as perceived by national and institutional stakeholders. METHODS:
      Qualitative interview study. Interview transcripts were coded and analysed
      independently by at least two researchers. Participants had opportunity to
      comment on their transcript and the manuscript. RESULTS: A total of 71 interviews
      were conducted with representatives of the media, specialist medical societies,
      consumer special interest groups, the Australian Red Cross Blood Service (ARCBS),
      government, private health insurers, technology manufacturers, prominent
      clinicians in the area and a sample of clinicians drawn from hospitals with
      variable use of blood-saving technologies. Technical advances and acceptance of
      lower transfusion triggers were identified as the main influences on the decrease
      in use of allogeneic blood transfusion in the past decade. Participants indicated
      that patients were most aware and supportive of autologous predonation.
      Participants noted that 'enthusiasts' were involved in educating about the need
      for alternatives, negotiating resourcing and maintaining the use of a technology.
      Funding mechanisms were seen as main barriers to use of alternatives. A
      discrepancy was noted in the rigour of evaluation and regulation of
      pharmaceuticals and devices/procedures. CONCLUSIONS: Uptake of blood transfusion
      technologies by institutions was dependent mostly on funding arrangements and the
      presence of an 'enthusiast'. Critical review of the evidence for effectiveness or
      cost-effectiveness of these technologies was rarely mentioned. Opportunities
      exist for evidence-based medicine principles to play a greater role in policy
      decisions in this area.

PMID- 11456037
TI  - Haemochromatosis: iron still matters.
AB  - Our ability to detect those predisposed to haemochromatosis is greatly enhanced
      by testing for HFE mutations. Ironically, this diagnostic advance has led to some
      confusion regarding the criteria for diagnosis of haemochromatosis, with
      overreliance on genetic testing instead of investigations for iron overload.
      Because many people who are homozygous for the C282Y mutation, or compound
      heterozygous for the C282Y and H63D mutations, either do not express or only
      partially express the disease, it is essential to confirm a diagnosis of
      haemochromatosis on the basis of increased body iron stores. Liver biopsy remains
      the best method of confirming this and has an important role in the patient with
      either borderline iron overload or advanced disease. Persistent elevation of
      serum ferritin concentration in the absence of overt liver damage, inflammation
      or neoplasia, and estimation of mobilized body iron by repeated phlebotomy, are
      reasonable alternatives to liver biopsy. Although the precise definition of iron
      overload is debated, a diagnosis of haemochromatosis cannot be made without
      demonstrating increased body iron stores.

PMID- 11456038
TI  - Australian Medical Council: a view from the inside.
AB  - Although it has an important role in maintaining medical standards, little is
      known about the work of the Australian Medical Council (AMC) by members of the
      medical profession. A non-statutory standards authority, the AMC accredits
      medical schools in Australia and New Zealand, examines overseas-trained doctors
      for registration purposes and advises Medical Boards and Health Ministers on
      registration issues. The AMC, in consultation with Specialist Medical Colleges
      and others, is currently working on a number of initiatives to ensure standards
      of medical training and practice, including procedures to recognize new
      specialties and to accredit externally specialist education and training courses.

PMID- 11456039
TI  - Checking the scoreboard: the impact of cancer genetics on clinical practice.
AB  - Improvements in cancer care have historically been predicated on significant
      scientific and technological advances, such as antisepsis in surgery, and the
      discovery of the therapeutic benefits of radiation and chemotherapeutic drugs.
      The past 30 years have seen an exponential increase in our knowledge of the
      biology and genetics of cancer, built on a massive and sustained research effort
      worldwide. Yet over the same period, significant changes in cancer outcomes have
      occurred largely as a result of public health measures and through incremental
      advances in existing technologies. The present paper examines the extent to which
      the new knowledge of cancer genetics has impacted on current patient care. It
      considers some of the issues that may have served to lessen this impact, as well
      as some of the reasons for this apparent imbalance between action and outcome.

PMID- 11456040
TI  - Influence of haemochromatosis gene mutations on treatment outcomes in patients
      with hepatitis C.

PMID- 11456041
TI  - Safe and effective use of chromatographically purified intravenous immunoglobulin
      despite profound anti-IgA sensitization.

PMID- 11456042
TI  - Catamenial haemoptysis as a result of endometrial embolism.

PMID- 11456043
TI  - Introduction of Dr. William C. Wood.

PMID- 11456044
TI  - Challenges facing clinical research.

PMID- 11456045
TI  - LaSalle D. Leffall, Jr., MD, FACS: the first Heritage Award winner, Society of
      Surgical Oncology.

PMID- 11456046
TI  - More is less: systemic treatment for local control in soft tissue sarcoma.

PMID- 11456047
TI  - A pilot study of preoperative chemoradiation for gastric cancer.

PMID- 11456048
TI  - Survival after induction chemotherapy and surgical resection for high-grade soft
      tissue sarcoma. Is radiation necessary?
AB  - BACKGROUND: Induction chemotherapy can produce dramatic necrosis in sarcomas
      raising the question of whether or not radiation is necessary. This study reviews
      the clinical outcome of a subset of patients with high-grade extremity soft
      tissue sarcomas (STS) who were treated with induction chemotherapy and surgical
      resection but without radiation. METHODS: Nonmetastatic, large, high-grade STS of
      the pelvis and extremities were treated with intra-arterial cisplatin,
      adriamycin, and, after 1995, ifosfamide. After induction, oncologic resection and
      histologic evaluation were performed. Good responders with good surgical margins
      were not treated with radiation. RESULTS: Thirty-three patients, with a median
      follow-up of 5 years, were included. Limb salvage rate was 94%. Median tumor
      necrosis was 95%. Four patients developed metastatic disease with three
      subsequent deaths. Two local recurrences occurred; both patients were salvaged
      with reresection and adjuvant external beam radiotherapy, although one died of
      metastatic disease 10 years later. Relapse-free and overall survival is 80% and
      88% at 5 and 10 years by Kaplan-Meier analysis. CONCLUSIONS: Intensive induction
      chemotherapy can be extremely effective for high-grade STS, permitting limb
      sparing surgery in lieu of amputation. Radiation may not be necessary if a good
      response to induction chemotherapy and negative wide margins are achieved. All
      patients with large, deep, high-grade STS of the extremities should be considered
      candidates for induction chemotherapy.

PMID- 11456049
TI  - Small bowel sarcoma: analysis of survival from the National Cancer Data Base.
AB  - BACKGROUND: Small bowel sarcomas (SBS) are rare, accounting for 10% of small
      bowel cancers. As a result, few studies of SBS have had enough patients to
      accurately define their natural history and to determine the factors that have an
      impact on patient survival. The objective of this study was to examine patient
      and tumor factors in SBS and to determine prognostic factors for disease-specific
      survival (DSS) using the National Cancer Data Base. METHODS: Data from the
      National Cancer Data Base for patients diagnosed with primary SBS between 1985
      and 1995 were analyzed. The chi2 statistic was used to determine significant
      differences between groups of patient, tumor, and treatment factors. DSS was
      calculated for patients diagnosed between 1985 and 1990. Significant differences
      in survival were determined using the Wilcoxon statistic for univariate analyses
      and by Cox regression in multivariate analyses. RESULTS: Of 14,253 small bowel
      tumors diagnosed between 1985 and 1995, sarcomas represented 10.1%. Overall, 5
      year DSS was 38.9%, with a median survival of 34.1 months (n = 590). By
      univariate analysis, patient age, sex, tumor size, tumor grade, histologic type,
      general summary stage, nodal status, and whether cancer-directed surgery was
      performed were significantly correlated with DSS. In multivariate analysis, tumor
      size <5 cm, leiomyosarcoma histology, and localized disease were found to be
      significant favorable prognostic factors for DSS. CONCLUSIONS: SBS are rare
      tumors that are challenging in terms of their histopathologic classification,
      grading, and staging. Patients with SBS were treated predominantly by surgery,
      with a minority receiving adjuvant therapy. Tumor size, histologic type, and
      general summary stage were independent prognostic factors for 5-year DSS in
      patients with SBS, which is improved relative to 5-year DSS seen in patients with
      small bowel adenocarcinoma.

PMID- 11456050
TI  - Amputation for recurrent soft tissue sarcoma of the extremity: indications and
      outcome.
AB  - BACKGROUND: Limb salvage after primary site failure of extremity soft tissue
      sarcoma is a challenging problem. Amputation may be the most effective treatment
      option in selected patients with local recurrence. We compared the outcome of
      patients treated with amputation versus limb-sparing surgery (LSS) for locally
      recurrent extremity sarcoma. METHODS: From 1982 to 2000, 1178 patients with
      localized primary extremity sarcoma underwent LSS. Of these, 204 (17%) developed
      local recurrence. Eighteen (9%) required major amputation and the remainder
      underwent LSS, of which 34 were selected for matched-pair analysis according to
      established prognostic variables. Rates of recurrence or death were estimated by
      the Kaplan-Meier method. Following adjustment for prognostic variables, a Mantel
      Haenszel test was used to compare the outcome between the two treatment groups.
      RESULTS: Patients in each group were well matched. All patients had high-grade
      tumors deep to the fascia. Median time to local recurrence was similar for both
      groups. Median follow-up was 95 months. Amputation was associated with a
      significant improvement in local control of disease (94% vs. 74%; P = .04). We
      observed no difference in disease-free (P = .48), disease-specific (P = .74), or
      overall survival (P = .93) between the two groups. Median postrecurrence survival
      was 20 months and 5-year OS was 36% for the entire study group. CONCLUSIONS: Limb
      sparing treatment achieves local control in the majority of recurrent extremity
      sarcomas for which amputation is infrequently indicated. Amputation improves
      local disease control but not survival under these circumstances.

PMID- 11456051
TI  - A pilot study of preoperative chemoradiotherapy for resectable gastric cancer.
AB  - BACKGROUND: The goals of this study were to assess the feasibility and toxicity
      of a regimen of preoperative chemoradiotherapy, surgery, and intraoperative
      radiotherapy in the treatment of patients with potentially resectable gastric
      cancer. A secondary objective was to assess pathologic response to
      chemoradiotherapy in the treated tumors. METHODS: Twenty-four patients were
      entered in the protocol. Treatment regimen consisted of 45 Gy of external beam
      radiotherapy with concurrent 5-FU given as a continuous infusion at a dose of 300
      mg/m2. Patients were restaged 4-6 weeks after chemoradiotherapy and then
      underwent surgical resection and intraoperative radiotherapy to a dose of 10 Gy.
      RESULTS: Twenty-three patients (96%) completed chemoradiotherapy in accordance
      with the study protocol. Nineteen (83%) of 23 patients who completed
      chemoradiotherapy underwent surgical resection with D2 lymphadenectomy. Four
      patients (17%) had progressive disease and were not resected. The morbidity and
      mortality rates were 32% and 5%, respectively. Of the resected patients, two
      (11%) had complete pathologic responses while 12 (63%) had pathologic evidence of
      significant treatment effect. CONCLUSIONS: Preoperative chemoradiotherapy for
      gastric cancer can be delivered safely and is well tolerated. The rate of
      surgical complications is consistent with that of other recently reported
      prospective trials of gastrectomy alone. Preoperative chemoradiotherapy resulted
      in significant pathologic responses in the majority of treated tumors, and
      complete pathologic responses were achieved in some patients.

PMID- 11456052
TI  - Evaluation of metastatic potential of gastric tumors by staining for
      proliferating cell nuclear antigen and chromosome 17 numerical aberrations.
AB  - BACKGROUND: Aberrations in chromosome 17 are important in carcinogenesis. We
      recently reported that numerical aberrations in chromosome 17 were associated
      with tumor progression in gastric cancer. The aim of this study was to determine
      the biological characteristics of gastric tumor cells with chromosome 17
      numerical aberrations. METHODS: Gastric tumor sections (n = 105) and metastatic
      lymph nodes (n = 16) were stained simultaneously for PCNA (proliferating cell
      nuclear antigen) and chromosome 17 centromere. Cancers were classified as
      follows: Group 1: PCNA(+) and numerical chromosomal aberration(+); Group 2: PCNA(
      ) and numerical chromosomal aberration(+); Group 3: PCNA(+) and numerical
      chromosomal aberration(-); and Group 4: PCNA(-) and numerical chromosomal
      aberration(-). RESULTS: The frequency of Group 1 cells correlated with lymphatic
      invasion (P < .0001), lymph node metastasis (P < .0001), and venous invasion (P <
      .01). The frequency of these cells in gastric lesions was lower than in
      metastatic lymph nodes (P < .01). Logistic regression analysis identified the
      depth of invasion followed by the frequency of Group 1 cells were two of the most
      significant independent factors that could predict lymph node metastasis and
      lymphatic invasion. CONCLUSIONS: The frequency of gastric tumor cells positive
      for PCNA and chromosome 17 numerical aberrations may be an indicator of the
      metastatic potential of gastric cancers.

PMID- 11456053
TI  - Bcl-2 is a useful prognostic marker in Dukes' B colon cancer.
AB  - BACKGROUND: Currently, the use of adjuvant therapy specifically in Dukes' B colon
      cancers is controversial, emphasizing the importance of identifying prognostic
      markers to select patients for such therapy. Bcl-2 plays an important role in
      apoptosis regulation of solid tumors, such as colon and breast cancer, and is
      normally expressed in the base of the colonic crypts. The purpose of this study
      is to determine whether or not bcl-2 expression can be used to predict survival
      in Dukes' B colon cancer patients. METHODS: Charts of 76 patients operated on at
      the Royal Victoria Hospital from 1986 to 1992 were reviewed. Bcl-2 staining was
      done with the avidin-biotin-peroxidase complex method using commercially
      available monoclonal bcl-2 antibodies. Two pathologists graded the intensity of
      bcl-2 staining on a scale of 0-3 and estimated the percentage of tumor cells
      staining positively (T-percent). Univariate and multiple regression of factors on
      overall survival (OS) and disease-free survival (DFS) was done with a Cox
      proportional hazards model and Kaplan-Meier survival curves. RESULTS: The mean
      age was 71.2 years, with 41 female and 35 male patients. Mean tumor size was 5.4
      cm with tumor grades of 19 well, 52 moderate, and 5 poorly differentiated. Tumors
      expressing bcl-2 had a similar DFS (P = .14) but a significantly improved OS (P =
      .04) compared with the bcl-2 negative tumors. The risk ratio for DFS was 0.49
      (95% CI, 0.19-1.26) and for OS was 0.35 (95% CI, 0.13-0.94). CONCLUSIONS: These
      data indicate that enhanced bcl-2 expression, specifically in Dukes' B colon
      carcinomas, is associated with improved survival. Thus, patients whose tumors do
      not express bcl-2 should be considered for adjuvant therapy.

PMID- 11456054
TI  - The definition of a sentinel node.

PMID- 11456055
TI  - Quality of life influenced by primary surgical treatment for stage I-III breast
      cancer-long-term follow-up of a matched-pair analysis.
AB  - BACKGROUND: Breast-conserving therapy has been demonstrated to be just as safe
      and a less disruptive experience compared with mastectomy for surgically
      manageable breast cancer. There is, however, no agreement in the literature about
      the impact of these procedures on several important aspects of quality of life
      (QOL). The purpose of the present study is to compare the long-term impact of
      these two surgical approaches on QOL in patients with identical tumor stages and
      to suggest possible shortcomings of the standard QOL questionnaires. METHOD:
      Between August 1999 and May 2000, QOL questionnaires were answered by 152 pair
      matched patients at the I. Frauenklinik, Ludwig-Maximilians University Munich, as
      part of routine follow-up examinations. The pairs of patients, each consisting of
      one patient after mastectomy and one after breast conservation, were selected
      according to the highest degree of equivalence in tumor stage. All patients had
      been initially treated for stage I-III breast cancer without evidence of distant
      metastases. The QOL was evaluated by using the QLQ-C30 questionnaire version 2.0
      of the EORTC Study Group on Quality of Life. We formulated seven additional
      questions about the patients' satisfaction with the primary surgical treatment
      modality as viewed from their current perspective. The QOL questionnaires were
      answered after a median interval of 46 months following primary treatment.
      RESULTS: Tumor stage, prognostic factors, and adjuvant systemic treatment were
      well balanced between the two groups. No differences between the two groups were
      observed in terms of all QOL items measured by the QLQ-C30. Our additional
      questions, however, revealed that patients in the mastectomy group were less
      satisfied with the cosmetic result of their primary operation (P < .0001), were
      more likely to feel basic changes in their appearance (P < .0001), and were more
      likely to be emotionally stressed by these facts (P < .0001). From their
      perspective at the time of completing the questionnaires, 11 patients in the
      mastectomy group (15%) would decide differently about the surgical treatment
      modality, compared with only 3 patients (4%) in the breast conservation group (P
      = .025). CONCLUSION: While the primary surgical treatment modality seems to have
      no long-term impact on general QOL, certain body-image-related problems may be
      caused by mastectomy. Standard measuring instruments for QOL may fail to detect
      differences in satisfaction and adaptation with the primary surgical treatment
      modality.

PMID- 11456056
TI  - MRI phenotype is associated with response to doxorubicin and cyclophosphamide
      neoadjuvant chemotherapy in stage III breast cancer.
AB  - BACKGROUND: The preferred management for women with stage II or locally advanced
      breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to
      chemotherapy has been shown to be an excellent predictor of outcome. Surrogates
      that can predict pathologic response and outcome will fuel future changes in
      management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC
      have distinct tumor patterns. We investigated whether or not these patterns
      predict response to therapy. METHODS: Thirty-three women who received neoadjuvant
      doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI
      scans before and after therapy were evaluated for this study. Response to therapy
      was measured by change in the longest diameter on the MRI. RESULTS: Five distinct
      imaging patterns were identified: circumscribed mass, nodular tissue infiltration
      diffuse tissue infiltration, patchy enhancement, and septal spread. The
      likelihood of a partial or complete response as measured by change in longest
      diameter was 77%, 37.5%, 20%, and 25%, respectively. CONCLUSIONS: MRI affords
      three-dimensional characterization of tumors and has revealed distinct patterns
      of tumor presentation that predict response. A multisite trial is being planned
      to combine imaging and genetic information in an effort to better understand and
      predict response and, ultimately, to tailor therapy and direct the use of novel
      agents.

PMID- 11456057
TI  - Sodium polyacrylate potentiates the anti-adhesion effect of a cellulose-derived
      polymer.
AB  - Available methods for postoperative adhesion prevention are insufficient. A
      previous study demonstrated that LM-200, a bioadhesive cellulose derivative was
      effective in reducing adhesions. Increasing the viscosity of a polymer solution
      enhances the tissue separating properties. Theoretically, a combination of sodium
      polyacrylate (PA) and LM-200 would give more viscous solutions than LM-200 alone,
      and thus be more efficacious. Therefore the efficacy of various combinations of
      LM-200 and PA was investigated. A lesion was created in the peritoneum of mice.
      The solutions to be tested, or saline, were given intraperitoneally. One week
      post-operatively, adhesion formation was quantified and expressed as a percentage
      of the original lesion covered with adhesions. PA (0.01 and 0.03 wt%) given
      separately did not differ in adhesion reducing effect from LM-200 (p = 0.3710 and
      0.3481) but PA (0.1 wt%) resulted in significantly less adhesion formation (p =
      0.0004). The effect of LM-200 increased significantly when adding PA (0.01 wt%)
      (p = 0.0007) or PA (0.03 wt%) (p < 0.0001). When adding PA (0.1 wt%) the effect
      was even more pronounced (p < 0.0001). The combination of a bioadhesive cellulose
      derivative and the polymer PA, was effective in reducing postoperative adhesion
      formation and a dose-dependent increase in efficacy was obtained compared to
      using the two components separately.

PMID- 11456058
TI  - Wear of HIPed and non-HIPed alumina-alumina hip joints under standard and severe
      simulator testing conditions.
AB  - Wear and the biological response to wear debris of artificial joints remain major
      concerns in total hip arthroplasty (THA). The long-term effects of UHMWPE wear
      debris are well documented and these have led to interest in alternate bearing
      materials for THA. Alumina ceramic-ceramic hip joints have been successfully used
      for more than 30 years with low wear and little incidence of osteolysis. The most
      common wear pattern observed on retrieved components is an elliptical wear
      'stripe' on the heads and a corresponding worn area on the cup with an
      approximated wear rate of 1-5 mm3 pa. More severe wear has also occasionally
      occurred, usually in association with an abnormal clinical history. Modern
      alumina-alumina THAs use an improved HIPed (hot isostatically pressed) alumina
      ceramic-bearing material which may be more resistant to severe wear. Previous in
      vitro simulator studies have not replicated in vivo wear rates or mechanisms. The
      aim of this study was to compare previous generation non-HIPed alumina and modern
      HIPed alumina in a hip joint simulator under 'normal' and 'harsh' testing
      conditions. HIPed alumina was found to have a lower wear rate than non-HIPed
      alumina, although the difference was not statistically significant at the 95%
      confidence level. Testing in Gelofusine and water lubricants did not elevate the
      wear rates of either material. Elevated swing phase load testing also had no
      significant effect on the wear rates of either material. Testing in the absence
      of any lubricant produced very severe wear of the non-HIPed material in one
      specimen only.

PMID- 11456059
TI  - Anodic oxide films containing Ca and P of titanium biomaterial.
AB  - Anodic oxidation and oxide films of titanium in the new electrolyte of calcium
      glycerophosphate (Ca-GP) and calcium acetate (CA) were investigated by
      galvanostatic mode, SEM, XRD and EPMA. The anodic oxide film displayed porosity,
      intermediate roughness, and high crystallinity. Also, the oxide film is enriched
      with Ca and P and high in thickness without microcracks. According to the surface
      properties of the oxide film, the optimum condition was that the concentration of
      the electrolyte was 0.02 M Ca-GP and 0.15 M CA, and current density and final
      voltage were 70 A/m2 and ca. 350 V. The oxide film formed in the condition is
      0.98 microm (Ra) rough, 5-7 microm thick, adhesive to the underlying substrate,
      and near 1.67 Ca/P ratio in the oxide film.

PMID- 11456060
TI  - Bone bonding behavior of the hydroxyapatite containing glass-titanium composite
      prepared by the Cullet method.
AB  - Bioactive composites composed of hydroxyapatite containing glass (HA-G) as a
      coating and titanium (Ti) or titanium alloy implants as a substrate were prepared
      by the Cullet method. This method results in the HA-G coating layer on the
      substrate with a compositional gradient in HA concentration. The results of in
      vitro and in vivo experiments investigating the characteristics of the composite
      materials are reported and discussed in this article. In vitro evaluations
      confirmed that the Cullet method was suitable for the preparation of the
      functionally gradient composite implants with higher reliable quality. In vivo
      experiments permitted evaluation of bonding strength of these composite implants
      to living bone tissue. Mechanical pull-out tests indicated that the implants
      bonded to living bone at least as firmly as those by the conventional method, and
      that the adhesion between the HA-G coating layer and metal substrate was well
      integrated and strongly maintained in vivo. SEM observations with EDX and a
      histological study of the interface between the HA-G-Ti composite implants and
      bone tissue revealed not only that the implants bonded to bone directly without
      any intervening tissue but that bone ingrowth into the HA-G layer occurred. The
      HA-G-Ti composite implants demonstrate both biocompatible and osteoconductive
      characteristics, and may be expected to obtain good and lasting results when
      applied clinically.

PMID- 11456061
TI  - Examination of in vivo influences on bioluminescent microbial assessment of
      corrosion product toxicity.
AB  - The composition of ionically dissolved and precipitated corrosion products from
      both free corrosion of ASTM F75 Co-Cr-Mo and galvanostatic polarization of Co-Cr
      Mo and F138 316L stainless steel was determined using differential pulse
      polarography and inductively coupled plasma atomic emission spectroscopy. A
      bacterial bioluminescence assay, Microtox, was used to assess the toxicity of the
      solid and dissolved corrosion products produced by galvanostatic polarization and
      the individual ions within them. The role of in vivo salinity, temperature, and
      protein content as modulators of corrosion product toxicity assessment was
      investigated empirically and mechanistically. Co-Cr-Mo products were found to be
      more toxic than those of 316L, and the most toxic ions were Cr6+, Ni2+, and Co2+.
      Ringer's solution potentiated the toxicity of the more toxic metal ions and
      reduced the toxicity of the less toxic ions. Using theoretical analysis in
      conjunction with experimental measurements, the ions in both alloys were found to
      interact in an antagonistic fashion. The presence of albumin was found to
      decrease metal toxicity, presumably by chelation.

PMID- 11456062
TI  - Novel microparticulate system made of poly(methylidene malonate 2.1.2).
AB  - Formulation of PMM 2.1.2 microparticles entrapping ovalbumin as a model protein
      was achieved by using a double emulsion solvent evaporation method. Parameters
      such as the nature of the solvent, polymer concentration and polymer molecular
      weight were investigated. Preparation process led to the formation of spherical
      and smooth particles with a mean diameter of 5 microm, and an encapsulation
      efficiency and protein loading level of up to 16 and 2.9% w/w, respectively.
      After an initial burst of approximately 10%, the protein was released at a rate
      of less than 1% per day. This slow release kinetics of encapsulated ovalbumin in
      phosphate buffer indicates that most of the protein was encapsulated within the
      polymer matrix. Degradation of PMM 2.1.2 microparticles in the presence of
      esterases indicated that side chain hydrolysis of the polymer was the rate
      determining step in bioerosion; cleavage of the ester side chain, which was
      further hydrolyzed to glycolic acid and ethanol, led to an acrylic acid and
      subsequent solubilization of the polymer. However, slow polymer backbone
      solubilization after degradation was observed.

PMID- 11456063
TI  - Synthesis and characterization of non-leaching biocidal polyurethanes.
AB  - The biocidal activities of a series of quaternized polyurethanes were examined
      against Staphylococcus aureus and Escherichia coli. The percentage of dead cells
      on a surface was found to depend on the alkyl halide used for quaternization, the
      concentration of quaternized moieties in the polyurethane, the gram-type of the
      microorganism, and the contact time of the organism with the surface. N,N-bis(2
      hydroxyethyl)isonicotinamide (BIN) was incorporated as the chain extender in a
      series of poly(tetramethylene oxide)-based polyurethane block copolymers. Three
      families of materials were synthesized that contained increasing hard segment
      fractions and therefore increasing concentrations of BIN. The pyridine ring in
      BIN was quaternized with a variety of alkyl halides to form cationic
      polyurethanes that possessed biocidal activity. The effect of quaternization on
      material properties was examined with tensile testing, water absorption analysis,
      and contact angle measurements. The antibacterial action of the polymers was
      investigated with zone of inhibition experiments and fluorescence microscopy,
      which was established as a reliable technique to determine the viability of
      organisms attached to a polymer surface.

PMID- 11456064
TI  - Structural characterization of phosphorylated chitosan and their applications as
      effective additives of calcium phosphate cements.
AB  - Chitosan was phosphorylated by P2O5 in methanesulfonic acid and the product as
      water-soluble phosphorylated chitosan (P-chitosans) was then characterized by
      phosphorus elemental analysis, IR and 31P-NMR spectroscopy. Two calcium phosphate
      cement (CPC) systems, i.e. (1) monocalcium phosphate monohydrate (MCPM) and
      calcium oxide (CaO) in 1 M phosphate buffer (pH = 7.4) and (2) dicalcium
      phosphate dihydrate (DCPD) and calcium hydroxide [Ca(OH)2] in 1 M Na2HPO4
      solution, were chosen to improve their mechanical properties by the addition of
      water-soluble P-chitosans with various values for molecular weight, degree of
      deacetylation (DD) and degree of substitution (DS). The results show that the
      compressive strength (CS) and Young's modulus of both CPC formulations after
      setting were obviously increased and setting time was slightly prolonged by
      adding water-soluble P-chitosan to the liquid phases. When a suitable amount of P
      chitosan was used, two improved CPC formulations were obtained with much better
      mechanical properties while the setting times were not longer than 15 min. The
      enhancement of compressive strength was due to high Ca2+-binding ability of
      phosphorylated chitosan, which could tightly bind the newly formed hydroxyapatite
      (HA) particles together by polymeric chains. It was noted that excessive addition
      of P-chitosan would lead to slow setting or no setting at all. The hardened CPC
      samples containing P-chitosan were characterized via X-ray diffraction spectra
      and scanning electron microscopy. Their leaching experiment was also carried out.
      The results indicated that P-chitosan-forced calcium phosphate cements have some
      good characteristics for clinical applications.

PMID- 11456065
TI  - Degradation and fracture of Ni-Ti superelastic wire in an oral cavity.
AB  - Superelastic Ni-Ti wire is widely used in orthodontic clinics, but delayed
      fracture in the oral cavity has been observed. Because hydrogen embrittlement is
      known to cause damage to Ti alloy systems, orthodontic wires were charged with
      hydrogen using an electro-chemical system in saline. Tensile tests were carried
      out, and fracture surfaces were observed after hydrogen charging. The strength of
      the Co-Cr alloy and stainless steel used in orthodontic treatment, was not
      affected by the hydrogen charging. However, Ni-Ti wire showed significant
      decreases in strength. The critical stress of martensite transformation was
      increased with increasing hydrogen charging, and the alloy was embrittled. The
      fractured surface of the alloys with severe hydrogen charging exhibited dimple
      patterns similar to those in the alloys from patients. In view of the galvanic
      current in the mouth, the fracture of the Ni-Ti alloys might be attributed to the
      degradation of the mechanical properties due to hydrogen absorption.

PMID- 11456066
TI  - Substrate affects the initial attachment and subsequent behavior of human
      osteoblastic cells (Saos-2).
AB  - Interaction between implant materials and bone cells contributes to the clinical
      success of dental implants. The object of this study was to investigate the
      initial attachment and subsequent behavior of human osteoblastic cells (Saos-2)
      to pure titanium (Ti), hydroxyapatite (HA), and glass. We, therefore, performed a
      time-course study for examining the area, attachment rate, distribution of focal
      adhesion kinase (FAK) vinculin, and actin, and the motility of Saos-2 cells on
      the materials. On Ti, cell area increased gradually, whereas on HA, cells spread
      quickly, but quitted spreading at 12 h after cell seeding. The number of cells on
      HA was greater than on the other materials. On Ti, the numbers of FAK- and
      vinculin-positive focal adhesions increased continuously. On HA, although the
      number of FAK-positive focal adhesions also increased continuously, the number of
      vinculin-positive focal adhesions decreased. Furthermore, actin staining showed
      that the cells on HA poorly formed stress fibers with weak polarity, whereas the
      cell on Ti possessed well-defined polarized stress fibers. On HA, cells started
      extension earlier than on Ti, motility was inactive, and the cells settled on the
      materials. These results suggest that the earlier settling of osteoblasts on HA
      might result in earlier osteogenesis on HA than other materials.

PMID- 11456067
TI  - Comparison of corrosion behaviour in presence of oral bacteria.
AB  - The aim of this study was to compare the resistance of the corrosion of dental
      alloys in a solution containing oral bacteria named Actinomyces viscosus
      (ATCC19246). In this paper, we explain the choice of this precise species of
      bacteria, then specify its culture in artificial saliva and the experimental
      precautions needed to avoid the pollution by other bacteria. The electrochemical
      behaviour of two dental alloys (Ni-Cr alloy and gold-based alloy) was
      investigated by electrochemical means in sterile Fusayama artificial saliva (AS),
      AS enriched with sterile yeast extract (YE) and YE modified by introducing
      bacteria (AV). Open-circuit potentials, potentiodynamic curves, polarization
      resistance and impedance spectroscopy are the electrochemical procedures selected
      for this work. It has thus been shown that the open-circuit potential of the non
      precious alloy is always lower than that of the gold precious alloy, and the
      colonization of metal surface by bacteria caused a drop in open circuit
      potential. The electrochemical impedance spectroscopy results have shown that the
      electrolyte resistance decreased between the AS, YE and AV milieu, in the
      presence of bacteria a slight decrease in polarization resistance was observed
      with the precious alloy and an increase with the non-precious alloy. The drop in
      the electrolyte resistance cannot explain the change in polarization resistance.
      The influence of Actinomyces viscosus might be essentially due to the consumption
      of oxygen at the metal/electrolyte interface of the specimen. For the non
      precious alloy, the absence of oxygen (instigator of corrosion) led to an
      increase in polarization resistance whereas the slight decrease for the precious
      alloys might be justified by the organic and inorganic metabolites released by
      bacteria in to the electrolyte. The scanning electron micrography after
      electrochemical analysis, confirmed the absence of contaminants. These
      preliminary results demonstrate the unquestionable influence of this bacteria on
      the corrosion behaviour of the alloys studied, however, further studies are
      necessary.

PMID- 11456068
TI  - Relation between cell density and the secretion of von Willebrand factor and
      prostacyclin by human umbilical vein endothelial cells.
AB  - In this study, the relation between the density of human umbilical vein
      endothelial cells (HUVECs) cultured on TCPS and (crosslinked) collagen, and the
      secretion of von Willebrand factor (vWF) and prostacyclin (PGI2) was determined.
      Collagen was crosslinked using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide
      (EDC) in combination with N-hydroxy-succinimide (NHS), resulting in a matrix
      containing 14 free primary amino groups per 1000 amino acid residues after
      crosslinking (E/N14C). HUVECs were seeded on E/N14C, non-crosslinked collagen (N
      Coll) and fibronectin-coated TCPS at densities ranging from 2500 to 50,000
      cells/cm2. After 1 day of culture, both basal and A23187-stimulated secretion of
      vWF (expressed per 1,000,000 cells) was considerably increased at low cell
      densities (i.e. below 5000 cells/cm2) on all substrates. Secretion of PGI2
      gradually increased with decreasing cell densities below 10,000 cells/cm2. After
      10 days of proliferation, cell numbers on all substrates exceeded 50,000
      cells/cm2, irrespective of the seeding density. Concomitantly, the initial higher
      secretion of PGI2 and vWF at the lowest seeding densities was decreased after
      longer times of culture, to values comparable to those obtained for higher
      seeding densities.

PMID- 11456069
TI  - Binding and release of basic fibroblast growth factor from heparinized collagen
      matrices.
AB  - Endothelial cell seeding is a promising method to improve the performance of
      small-diameter vascular grafts. Growth of endothelial cells seeded on the luminal
      surface of synthetic vascular grafts, coated with a matrix suitable for cell
      seeding (e.g. collagen), can be accelerated by local, sustained release of basic
      fibroblast growth factor (bFGF). In this study two potential matrices for in vivo
      endothelial cell seeding were studied with respect to bFGF binding and release:
      collagen crosslinked using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC)
      and N-hydroxysuccinimide (NHS), as well as heparinized EDC/NHS-crosslinked
      collagen. bFGF binding was determined after incubation of circular samples (10 mm
      diameter) with 0.25 ml bFGF solution for 90 min. Immobilization of increasing
      amounts of heparin, also using EDC and NHS, to crosslinked collagen containing 14
      free primary amino groups per 1000 amino acid residues (E/N14C) resulted in
      binding of increasing amounts of bFGF. A plateau in bFGF binding was observed for
      heparinized E/N14C containing approximately 2.0-3.0 wt% of immobilized heparin
      which was obtained using a molar ratio of EDC to heparin-carboxylic acid groups
      of 0.4 during heparin immobilization (E/N14C-H(0.4)). At concentrations up to 840
      ng bFGF/ml, 10% of the added bFGF bound to E/N14C, while binding of bFGF to
      E/N14C-H(0.4) amounted to 22%. Both E/N14C and E/N14C-H(0.4) pre-loaded with bFGF
      showed sustained bFGF release. A burst release of 30% in endothelial cell culture
      medium (CM) was observed for E/N14C during the first 6 h, compared to 2% release
      from E/N14C-H(0.4). After 28 days, the bFGF release from E/N14C and E/N14C-H(0.4)
      in CM amounted to 100 and 65%, respectively. Combined results of binding and
      release of bFGF indicate that compared to E/N14C, E/N14C-H(0.4) is the substrate
      of choice for bFGF pre-loading and subsequent endothelial cell seeding.

PMID- 11456070
TI  - Static and dynamic in vitro study of a sol-gel glass bioactivity.
AB  - A comparative study of in vitro bioactivity of a sol-gel glass with composition
      55% SiO2-41%CaO-4%P2O5 has been carried out by soaking it in a simulated body
      fluid (SBF) with and without exchange of this solution. When SBF is kept constant
      (static assay) the solution composition changes, increasing the Ca2+
      concentration and pH as a function of soaking time while these parameters remain
      nearly constant and very close to human conditions in dynamic conditions. Glass
      surface is studied by FTIR, XRD and SEM in order to compare the behaviour in the
      two procedures, revealing that in both cases an apatite-like layer is formed on
      the glass surface, although there are differences in rate and morphology in this
      formation. In addition, a study of porosity was carried out by Hg intrusion
      pointing out the pore distribution and changes in porosity with time for both
      procedures. A similar behaviour in mesopore region was detected, while macropores
      remain nearly constant in static conditions, decreasing from 0.48 to 0.12 microm
      in just 3 h of soaking in dynamic assay.

PMID- 11456071
TI  - Protein adsorption and monocyte activation on germanium nanopyramids.
AB  - Germanium can form defect-free pyramidal islands on Si(1 0 0)-2 x 1 with a height
      of 15 nm and a width of 60 nm. Using chemical vapor deposition we have prepared
      substrates with different nanopyramid densities to study the impact on contact
      angles, protein adsorption and cell behavior. The advancing contact angle of a
      water droplet of millimeter size significantly raises with nanopyramid density.
      The dynamic contact angle measurements reveal that the substrate surface is
      highly hydrophilic. On such a surface the adsorption of hydrophilic proteins,
      i.e. albumin and globulin, is drastically increased by the presence of
      nanopyramids. More important, however, the globulin is inactive after adsorption
      on nanopyramid edges. This observation is supported by the cytokine release of IL
      1beta and TNF-alpha of monocyte-like cell line U937. Consequently, the presence
      of nanopyramidal structures gives rise to less inflammatory reactions.

PMID- 11456072
TI  - Evaluation of a treatment-appropriate cognitive intervention for challenging
      alcohol outcome expectancies.
AB  - The current study evaluated an alcohol expectancy challenge (EC) that did not
      require alcohol administration and could therefore be implemented in a treatment
      setting. Participants in the treatment group directly challenged alcohol
      expectancies endorsed on an expectancy questionnaire. A total of 62 male and
      female undergraduates completed the study (32 control participants, 30 EC
      participants). Self-report questionnaires were collected pre- and post
      intervention, and alcohol logs were kept during the study. The EC resulted in
      significant reductions in alcohol expectancies across multiple expectancy
      dimensions. Although the analysis for alcohol consumption was not significant,
      there was a trend toward better outcomes for male participants in the EC
      condition. In contrast to study hypotheses, women in the EC condition increased
      their alcohol consumption from pre to post-test to a greater degree than did
      control participants.

PMID- 11456073
TI  - Behavioral and cognitive-behavioral treatments for alcoholism: research
      opportunities.
AB  - This status report on behavioral and cognitive-behavioral treatments (CBT) for
      alcoholism is based on an article commissioned by the National Institute on
      Alcohol Abuse and Alcoholism (NIAAA) for a review of its treatment research
      priorities. A number of gaps in knowledge and consequent research opportunities
      were identified. Additional work on cue exposure is needed to identify the most
      potent cues for drinking, and strategies for reducing the impact of drinking
      cues. Regarding contingency management, there is need for further studies with
      alcoholics, investigation of reinforcement schedules, and exploration of
      maintenance factors. With respect to the community reinforcement approach (CRA),
      research should identify its most effective elements and ways to sustain gains
      following treatment. The mediating role assigned to coping skills in the
      cognitive-behavioral model needs to be substantiated, and the effectiveness of
      various coping skills components must be determined. Further studies of relapse
      prevention (RP) are needed to improve the system for classifying relapse
      episodes, and to identify the most effective interventions for each type of
      episode. Studies of behavioral marital therapy should include identifying active
      ingredients, and testing hypothesized mediators of change. Patient-treatment
      matching strategies may help to identify clients likely to benefit from these
      strategies. Finally, given the overlap among these approaches, it is likely that
      research along the lines suggested will impact several of them and lead to a
      consolidation of their most effective elements into a common treatment package.

PMID- 11456074
TI  - The relationship between thought suppression and smoking cessation.
AB  - Intrusive thoughts (e.g., anxiety, depression, substance use) are among the most
      salient symptoms of clinical problems. Therefore, methods of thought suppression
      have received considerable attention. However, some studies have found that
      attempts to suppress thoughts precipitate an increase in thoughts. In the case of
      substance abuse, such thoughts could serve as cues for further use. This study
      examined the association between thought suppression and quitting smoking in a
      sample of current and ex-smokers. Using the White Bear Suppression Inventory
      (WBSI), scores were obtained for participants' level of thought suppression.
      Based on the idea that a greater tendency to suppress thoughts would make
      quitting smoking more difficult, it was hypothesized that unsuccessful quitters
      would have higher WBSI scores than smokers who had successfully quit. It was
      found that mean scores on the WBSI were significantly higher (P<.05) for smokers
      than ex-smokers. These findings suggest that a tendency toward thought
      suppression may increase the likelihood that attempts to quit smoking will be
      unsuccessful.

PMID- 11456075
TI  - Predictors of smoking cessation from adolescence into young adulthood.
AB  - Although smoking cigarettes is hazardous to health and cessation has positive
      health benefits, few smokers are able to successfully quit. The purpose of this
      study was to examine the predictors of smoking cessation in a nonclinical sample
      of 134 male and 190 female, young adult, regular (daily) smokers within a social
      learning and maturing-out framework. Four waves of prospective, longitudinal data
      from a community sample followed from adolescence into young adulthood were
      analyzed. Logistic regression analyses were used to test the effects of
      differential associations, definitions, differential reinforcement, and changes
      in adult role status on smoking cessation in young adulthood. Becoming married to
      a nonsmoker and decreases in the proportion of friends who smoked were
      significant predictors of cessation. Current smokers and stoppers did not differ
      significantly in terms of prior intensity of cigarette use or alcohol
      abuse/dependence. They also did not differ in terms of psychological
      characteristics, including depression and prior coping use of cigarettes. Social
      networks were more important than social roles for predicting cessation in young
      adulthood. Thus, smoking cessation programs should focus on social learning
      processes.

PMID- 11456076
TI  - Smoking acquisition among adolescents and young Latinas: the role of
      socioenvironmental and personal factors.
AB  - This paper examined the effects of socioenvironmental and personal factors on two
      stages of the smoking continuum--onset of smoking and regular smoking--among a
      sample of 1411 Latina clients, ages 14-24, at two federally funded family
      planning clinics. The socioenvironmental factors included cultural indicators,
      smoking behavior of family and peers, and norms. The personal factors were risk
      taking behaviors and intention to smoke in the future. Results showed that the
      indicators associated with experimentation were different than those linked with
      regular smoking. Socioenvironmental factors associated with the transition from
      never having smoked to trying cigarettes included acculturation, as measured by
      language and familialism, and peer smoking behavior. Among the personal factors,
      risk-taking behavior (past use of drugs, alcohol, and general risk attitude) and
      smoking intentions were correlates of experimentation. The transition from
      experimenter to regular smoker was associated with peer smoking behavior (P< .05)
      in the socioenvironmental domain and drug use and intention to smoke in the
      future among the personal factors (both P values <.001). Age, years of education,
      marital status, norms, and parental smoking did not independently predict either
      of the smoking outcomes. Intention to smoke was the strongest predictor of
      experimentation (OR = 8.3, Cl 5.87-11.60) and regular smoking (OR= 19.9, CI 12.31
      29.21) and could help identify those most likely to benefit from smoking
      prevention and cessation interventions.

PMID- 11456077
TI  - Stage of change, decisional balance, and temptations for smoking: measurement and
      validation in a large, school-based population of adolescents.
AB  - Developing interventions for reducing adolescent smoking rates based on the
      Transtheoretical Model (TTM) requires the development of quality measures of the
      key constructs of the model. The goal of this investigation was to evaluate the
      psychometric properties of measures of Stage of Change, Decisional Balance and
      Situational Temptation for both smokers and nonsmokers and to test if the
      predicted relationships between these constructs were confirmed in a large
      (N=2808) sample of adolescents. A correlated three factor model (Social Pros,
      Coping Pros and Cons) provided an excellent fit to the 12-item Decisional Balance
      inventory for both smokers (CFI=0.957) and nonsmokers (CFI=0.963). A hierarchical
      four factor model (negative affect, positive social, habit strength and weight
      control) provided an excellent fit to the eight-item Situational Temptations
      inventory for smokers (CFI=0.969). A hierarchical five-factor model (same four as
      smokers plus Curiosity) provided an excellent fit to the 10-item Situational
      Temptations inventory for nonsmokers (CFI=0.943). The relationships between both
      the Decisional Balance and temptation scales and the Stages of Change were
      verified for both smokers and nonsmokers. The measures for adolescents are
      similar to but not the same as the measures of these constructs for adults.

PMID- 11456078
TI  - Temptation, restriction, and alcohol consumption among American and German
      college students.
AB  - To assess relationships between alcohol consumption and two dimensions of
      drinking restraint (temptation and restriction), American and German college
      students were given the Khavari Alcohol Test (KAT) and the Temptation and
      Restraint Inventory (TRI). As hypothesized, drinking temptation was a positive
      predictor of students' alcohol consumption in both countries, but there was no
      main effect for drinking restriction. Also as hypothesized, American students who
      were high on drinking temptation drank greater (not smaller) quantities of
      alcohol if they were also high on drinking restriction. Conversely, German
      students who were high on drinking temptation drank more alcohol if they were
      also low on drinking restriction. The results point to cross-cultural
      similarities and differences in relationships between drinking temptation and
      restriction and actual alcohol consumption.

PMID- 11456079
TI  - Evaluating a population-based recruitment approach and a stage-based expert
      system intervention for smoking cessation.
AB  - A stage-matched expert system intervention was evaluated on 4144 smokers in a two
      arm randomized control trial with four follow-ups over 24 months. Smokers were
      recruited by random digit-dial calls, and 80.0% of the eligible smokers were
      enrolled. Individualized and interactive expert system computer reports were sent
      at 0, 3, and 6 months. The reports provided feedback on 15 variables relevant for
      progressing through the stages. The primary outcomes were point prevalence and
      prolonged abstinence rates. At 24 months, the expert system resulted in 25.6%
      point prevalence and 12% prolonged abstinence, which were 30% and 56% greater
      than the control condition. Abstinence rates at each 6-month follow-up were
      significantly greater in the Expert System (ES) condition than in the comparison
      condition with the absolute difference increasing at each follow-up. A proactive
      home-based stage-matched expert system smoking cessation program can produce both
      high participation rates and relatively high abstinence rates.

PMID- 11456080
TI  - Substance Dependence Severity Scale: reliability and validity for ICD-10
      substance use disorders.
AB  - The Substance Dependence Severity Scale (SDSS) is a semistructured interview that
      assesses the severity of the DSM-IV diagnoses of dependence and abuse and the ICD
      10 diagnoses of substance dependence and harmful use across a wide range of
      substances. Previous research has demonstrated that the SDSS' DSM-IV dependence
      scales are reliable and valid indicators of diagnostic severity. However, the ICD
      10 scales have not been psychometrically tested. This study investigated the test
      retest reliability, internal consistency, diagnostic concordance, and concurrent
      validity of the SDSS' ICD-10 dependence and harmful use scales in 180 (112 male
      and 68 female) treated substance users. Test-retest reliabilities for the ICD-10
      dependence scales ranged from good to excellent for alcohol, cocaine, heroin, and
      cannabis. Test-retest reliabilities for the SDSS' ICD-10 harmful use scales were
      in the good range for alcohol, cocaine, and heroin and the poor to fair range for
      cannabis. Internal consistency, diagnostic concordance, and concurrent validity
      results were comparable to the test-retest findings. These results support the
      use of the SDSS for assessing the severity of the ICD-10 dependence and harmful
      use diagnoses.

PMID- 11456081
TI  - Concordance between verbal report and urine screen of recent marijuana use in
      adolescents.
AB  - This study compared the concordance of self-report for recent marijuana use with
      results obtained from urine drug screen. The sample consisted of adolescent sons
      of fathers with DSM-III-R lifetime substance use disorder (SUD) [high average
      risk (HAR); N= 75] and sons of fathers with no Axis 1 psychiatric or SUD [low
      average risk (LAR); N= 125]. To avoid recall bias, and to ensure that the
      timeframe for accurate detection was restricted to promote accuracy, urine drug
      screen results were compared to self-reported marijuana use during the prior 48 h
      using an interview format. The HAR group of adolescents reported a higher rate of
      recent cannabis use and also had a higher rate of cannabis detection as measured
      in urine. The two groups did not differ with respect to either over or under
      reporting marijuana use. Overall, of 19 participants who obtained positive urine
      cannabis results, six (31.5%) verbally denied that they used marijuana within the
      previous 2 days. Among the 181 participants who obtained a negative urine drug
      screen, 20 subjects (11.5%) inaccurately asserted that they had used marijuana
      within the prior 2 days. In total, 13% of the participants (26/200) inaccurately
      reported recent cannabis use. These results underscore the need for caution in
      interpreting the results of self-report methods documenting the prevalence of
      drug use among youth.

PMID- 11456082
TI  - Purification and characterization of ginsenoside-beta-glucosidase from ginseng.
AB  - The ginsenoside-beta-glucosidase that hydrolyzes the beta-(1-->2)-glucoside of
      the ginsenoside Rg3 sugar moiety to ginsenoside Rh2 was isolated from the ginseng
      root, and the enzyme was purified and characterized. The enzyme was purified to
      one spot in SDS polyacrylamide gel electrophoresis, and its molecular weight was
      about 59 kDa. The optimum temperature of the ginsenoside-beta-glucosidase was 60
      degrees C, and the optimum pH was 5.0. Ca2+ ion had positive effect on
      ginsenoside-beta-glucosidase, while Cu2+ had negative effect on it. The
      ginsenoside-beta-glucosidase may be a special beta-glucosidase that is different
      from the original exocellulase such as beta-glucosidase (EC 3.2.1.21).

PMID- 11456083
TI  - 4-(Benzoylindolizinyl)butyric acids; novel nonsteroidal inhibitors of steroid
      5alpha-reductase. III.
AB  - A novel series of indolizinebutyric acids with various benzoyl substituents was
      synthesized to develop nonsteroidal inhibitors of steroid 5alpha-reductase, and
      the structure-activity relationships in this series were studied. We previously
      reported the structure-activity relationships in a series of indolebutyric acids
      as well as the discovery of the novel nonsteroidal 5alpha-reductase inhibitor,
      FK143. We have now made other modifications to this compound to improve in vivo
      inhibitory activity. By altering the heterocyclic nucleus and changing the
      benzoyl substituent we have succeeded in identifying the strongly active
      compound, FK687, (S)-4-[1-[4-[[1-(4-isobutylphenyl)butyl]oxy]benzoyl]indolizin-3
      yl]butyric acid, which displays strong in vitro inhibitory activity against the
      human enzyme and in vivo inhibitory activity against the castrated young rat
      model. This compound should be a useful agent for the treatment of benign
      prostatic hyperplasia.

PMID- 11456084
TI  - New hemisynthetic manoyl oxide derivatives with antimicrobial activity.
AB  - The synthesis and antimicrobial activity of ten labdane-type diterpenes derived
      from ent-3-beta-hydroxy-13-epi-manoyl oxide (ribenol) is reported. The
      chloroethyl carbamidic ester 9 showed the strongest antimicrobial activity
      against all the tested gram (+), gram (-) bacteria and pathogenic fungi.
      Moreover, the glycoside 11 exhibited an interesting activity against the three
      tested fungi.

PMID- 11456085
TI  - The inclusion compound of a new ionizable derivative of beta-cyclodextrin with
      ferrocenium drug.
AB  - A new beta-cyclodextrin (beta-CD) derivative, mono[6-deoxy-6-(2-butenedinitrile
      2,3-dimercapto sodium salt)]-beta-CD (6-mnt-beta-CD), and its inclusion compound
      with a ferrocenium drug, have been prepared and characterized by IR, UV, 13C-NMR
      spectroscopy, and mass spectrometry, elemental analysis, thermogravimetry, and
      cyclic voltammetry (CV). The interplay between the side-arm anion of beta-CD and
      the ferrocenium (guest) in the inclusion compound 6-mnt-beta-CD-/Fc+ has been
      investigated by 13C-NMR, UV, IR, and thermogravimetric methods. Charge transfer
      from the anion to the cation in 6-mnt-beta-CD-/Fc+ was then experimentally
      identified. The interaction between the guest and the host with side-arm in 6-mnt
      beta-CD-/Fc+ resulted in smaller positive potential shifts compared to that in
      the inclusion compound [beta-CD/Fc+]BF4-.

PMID- 11456086
TI  - Studies on new platelet aggregation inhibitors 1. Synthesis of 7-nitro-3,4
      dihydroquinoline-2(1H)-one derivatives.
AB  - A series of 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-ones were
      prepared and tested for platelet aggregation inhibitory effect, cardiotonic
      activity and chronotropic activity. These compounds appeared to show selective
      inhibitory activity against platelet aggregation. Among them, 6-(4
      ethoxycarbonylpiperidino)-7-nitro-3,4-dihydroquinoline-2(1H)-one (22f) showed the
      most potent inhibitory activity and high selectivity. A divergent synthetic route
      to 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives
      has also been investigated.

PMID- 11456087
TI  - Structure-activity relationships of N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N'
      (3,4-dimethylphenyl)piperazine and analogues as inhibitors of acyl-CoA:
      cholesterol O-acyltransferase.
AB  - A novel series of acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors were
      synthesized from a lead compound, 1-(4-hydroxy-3-methoxyphenyl)-7-phenylhept-1-en
      3-one (1, Yakuchinone B) through a modification of three regions (A, B, C) in the
      molecule. In this study, the compounds prepared were tested for in vitro
      inhibitory activity on microsomal ACAT from the liver of rats and for in vivo
      hypocholesterolemic activity in rats given a high cholesterol diet. N-(3,5
      Dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine (45), which
      belongs to the amide compounds, has finally been discovered. Compound 45
      inhibited rat hepatic ACAT in a more striking manner than CI-976, an amide
      compound ACAT inhibitor, and it exhibited a high level of hypocholesterolemic
      activity in vivo. Since 45 strongly inhibited both microsomal ACAT prepared from
      HepG2 (a cell line derived from human hepatocarcinoma) and Caco2 (a cell line
      derived from human colon adenocarcinoma), there is speculation that 45 might have
      the ability to inhibit ACAT in both the human intestine and liver independent of
      the difference in the distribution of ACAT isozymes. On the other hand, 45 did
      not induce adrenotoxicity in subacute toxicity studies in rats. These results
      suggest that it has promise for development as a new therapeutic agent for
      hypercholesterolemia and atherosclerosis.

PMID- 11456088
TI  - Water-soluble constituents of ajowan.
AB  - From the water-soluble portion of the methanol extract of the fruit of Carum
      ajowan (ajowan), which has been used as a spice and medicine, 25 compounds,
      including five new monoterpenoid glucosides, a new monoterpenoid, two new
      aromatic compound glucosides, and two new glucides, were obtained. Their
      structures were clarified by spectral investigation.

PMID- 11456089
TI  - Medicinal foodstuffs. XXIV. Chemical constituents of the processed leaves of
      Apocynum venetum L.: absolute stereostructures of apocynosides I and II.
AB  - Two new ionone glucosides, named apocynosides I and II, were isolated from the
      roasted leaves of Apocynum venetum L. together with nine known compounds. The
      absolute stereostructures of apocynosides I and II were determined by chemical
      and physicochemical evidence, which included the application of a modified
      Mosher's method and the circular dichroism helicity rule.

PMID- 11456090
TI  - The reaction of (4R,5R)- and (4S,5S)-4,5-epoxy-2(E)-hexenoates and secondary
      amines.
AB  - A reaction of methyl (4R,5R)-4,5-epoxy-2(E)-hexenoate 1 with N-benzylmethylamine
      gave a diastereomerically pure methyl (4R,5R)-4,5-epoxy-(3S)-N-benzylmethylamino
      hexanoate 6 and methyl (4S,5R)-4-N-benzyl-methylamino-5-hydroxy-2(E)-hexenoate 7.
      The former was chemoenzymatically converted to (-)-osmundalactone 11, which is an
      aglycone of osmundalin. On the other hand, the directly conjugated addition of
      dimethylamine to methyl (4S,5S)-4,5-epoxy-2(E)-hexenoate 1 followed by treatment
      with MeOH at 40 degrees C exclusively provided methyl (4R,5S)-4-dimethylamino-5
      hydroxy-2(E)-hexenoate 16, which was converted into L-(-)-forosamine 18.

PMID- 11456091
TI  - New rearranged clerodane diterpenes from Tinospora baenzigeri.
AB  - Baenzigeroside B, a new rearranged clerodane diterpene glucoside, was isolated
      from the stems of Tinospora baenzigeri. The aglycone of baenzigeroside B,
      baenzigeride B (isolated as its acetate), was found together with baenzigeride A,
      baenzigerosides A and B in the leaves of the same plant. Baenzigeride B and
      baenzigeroside B are the first examples of a new class of rearranged clerodane
      diterpenes. The possible biogenesis of the compounds is discussed.

PMID- 11456092
TI  - Stilbenoids in lianas of Gnetum parvifolium.
AB  - Five new stilbene dimers were isolated from the lianas of Gnetum parvifolium in
      addition to known stilbenoids. The structures of the compounds were established
      on the basis of spectroscopic evidence, including long-range coupling and nuclear
      Overhauser effect experiments, in NMR spectrum. Among the isolates, 2b
      hydroxyampelopsin F showed potent inhibitory activity in the Maillard reaction.

PMID- 11456093
TI  - Medicinal flowers. III. Marigold. (1): hypoglycemic, gastric emptying inhibitory,
      and gastroprotective principles and new oleanane-type triterpene oligoglycosides,
      calendasaponins A, B, C, and D, from Egyptian Calendula officinalis.
AB  - The methanolic extract and its 1-butanol-soluble fraction from the flowers of
      Calendula officinalis were found to show a hypoglycemic effect, inhibitory
      activity of gastric emptying, and gastroprotective effect. From the 1-butanol
      soluble fraction, four new triterpene oligoglycosides, calendasaponins A, B, C,
      and D, were isolated, together with eight known saponins, seven known flavonol
      glycosides, and a known sesquiterpene glucoside. Their structures were elucidated
      on the basis of chemical and physicochemical evidence. The principal saponin
      constituents, glycosides A, B, C, D, and F, exhibited potent inhibitory effects
      on an increase in serum glucose levels in glucose-loaded rats, gastric emptying
      in mice, and ethanol- and indomethacin-induced gastric lesions in rats. Some
      structure-activity relationships are discussed.

PMID- 11456094
TI  - Halofantrine-phospholipid interactions: monolayer studies.
AB  - The antimalarial agent halofantrine penetrates dipalmitolylphosphatidylcholine
      (DPPC) monolayers resulting in an increase in surface pressure and an expansion
      in area occupied by the lipid components of the monolayer. This phenomenon is
      observed at concentrations (0.05-0.2 microm) of halofantrine that have no surface
      activity. Penetration increases with drug concentration and is greatest at low
      initial surface pressures of the monolayer. A critical surface pressure of the
      DPPC monolayer has been determined from constant area and constant pressure
      conditions. The magnitude of these values support the hypothesis that
      halofantrine readily penetrates the DPPC monolayers. The presence of cholesterol
      in the DPPC monolayer hampers penetration and a lower critical surface pressure
      is obtained under such conditions. Even then, a slower rate of penetration is
      observed only in monolayers maintained at high initial surface pressures (10, 15
      mN/m), corresponding to the liquid condensed phase of the monolayer, and not at
      low surface pressures (2.5, 5.0 mN/m). These results help to give a better
      understanding of the dynamics of the halofantrine-phospholipid interaction as
      well as the pharmacodynamic character of the drug.

PMID- 11456095
TI  - Chemical constituents of Prangos tschiniganica; structure elucidation and
      absolute configuration of coumarin and furanocoumarin derivatives with anti-HIV
      activity.
AB  - The methanol extract of the dried aerial parts of Prangos tschimganica gave three
      new coumarin derivatives and 30 known coumarin derivatives. Their structures were
      established on the basis of chemical and spectroscopic evidence. Absolute
      configuration of the isolated compounds were determined by using a modified
      Mosher's method. Some of the isolated compounds showed anti-HIV activity.

PMID- 11456096
TI  - Novel syntheses of murrayaquinone A and furostifoline through 4-oxygenated
      carbazoles by allene-mediated electrocyclic reactions starting from 2
      chloroindole-3-carbaldehyde.
AB  - The formal total synthesis of murrayaquinone A (1) and the total synthesis of
      furostifoline (5) were completed by the construction of 4-oxygenated 3
      methylcarbazoles 7 based on a new type of electrocyclic reaction through 2
      alkenyl-3-allenylindole intermediates 8 derived from the 2-alkenyl-3
      propargylindoles 9, starting from 2-chloroindole-3-carbaldehyde (11). The N,O
      bisbenzyloxymethyl group of 16c and 22 underwent a Birch reduction followed by
      treatment with Triton B to produce the known 4-hydroxy-3-methylcarbazole (7a) and
      4-hydroxy-3-methylfuro[3,2-a]carbazole (7b) as precursors of murrayaquinone A (1)
      and furostifoline (5), respectively. The trifluoromethanesulfonyloxy-3
      methylfuro[3,2-alcarbazole (24), prepared from 7b, was subjected to reductive
      cleavage to provide furostifoline (5).

PMID- 11456097
TI  - Caffeoyl, coumaroyl, galloyl, and hexahydroxydiphenoyl glucoses from Balanophora
      japonica.
AB  - Eighteen new and sixteen known acyl glucoses having caffeoyl, coumaroyl, galloyl,
      and hexahydroxydiphenoyl groups were isolated from a medicinal parasitic plant,
      Balanophora japonica. Their structures were determined by spectroscopic and
      chemical methods. Caffeoyl ellagitannins, which have been rarely found in nature,
      were major phenolic constituents of this plant, and this is the first report of
      the isolation of ellagitannins from Balanophoraceae.

PMID- 11456098
TI  - Diels-Alder cycloadditions of 2(1H)-quinolones having an electron-withdrawing
      group at the 3-position acting as dienophiles with dienes.
AB  - Diels-Alder cycloadditions of 2(1H)-quinolones having an electron-withdrawing
      group at the 3-position with alkyl- and silyloxy-1,3-butadienes (2a,b) were
      carried out to give phenanthridones richly functionalized regio- or
      stereoselectively under conditions of atmospheric and high pressure. Furthermore,
      regioselectivity and chemoselectivity of 3-substituted 2(1H)-quinolones to 2a, b
      were examined using MO calculation.

PMID- 11456099
TI  - Diels-Alder reaction of 1,3-butadiene derivatives with 1-methyl-2(1H)-quinolones
      having an electron-withdrawing group at the 4-position.
AB  - Diels-Alder reactions of 1-methyl-2(1H)-quinolones having an electron-withdrawing
      group at the 4-position with isoprene, butadiene sulfone, and cyclohexadiene were
      performed to yield functionalized phenanthridones stereoselectively at
      atmospheric and at high pressure. Regioselectivity and stereochemistry of a
      methoxycarbonyl group were studied using the semi-empirical and ab initio MO
      methods, respectively.

PMID- 11456100
TI  - Separation of sympathomimetic amines of abuse and related compounds by micellar
      electrokinetic chromatography.
AB  - Separation of twelve sympathomimetic amines and related compounds by micellar
      electrokinetic chromatography (MEKC) with UV absorbance detection is described.
      These amines were well separated within 25 min using 50 mM sodium tetraborate
      solution containing 15 mM sodium dodecylsulfate (SDS) of pH 9.3 as a running
      solution and detected at 210 nm. MEKC was performed with an applied voltage of 13
      kV at 25 degrees C using a fused-silica capillary (50 cm x 75 mm i.d.) with
      effective length of 37.5 cm. The detection limits of these compounds were in the
      range from 4 to 97 fmol/injection at a signal-to-noise ratio (S/N) of 3. The
      reproducibility of the method expressed as relative standard deviation (RSD) for
      within-day (n=6) and between-day (n=5) assays was less than 4.8 and 8.8%,
      respectively. The proposed method could be applied to the determination of an
      anorectic drug, phentermine, in Chinese tea with a detection limit of 99 microg/g
      (105 fmol/injection, S/N=3).

PMID- 11456101
TI  - Synthesis and fungicidal activities of silicon-containing derivatives of 2-aryl-3
      (1H-1,2,4-triazol-1-yl)propanenitriles.
AB  - A new series of silicon-containing derivatives of 2-aryl-3-(1H-1,2,4-triazol-1
      yl)propanenitriles were synthesized and evaluated for fungicidal activities
      against rice sheath blight and powdery mildew on cucumber. These derivatives
      exhibited higher efficacy than reference fungicides.

PMID- 11456102
TI  - Two new monoterpene peroxide glycosides from Aster scaber.
AB  - The aerial part of Aster scaber Thunb. (Asteraceae) yielded two new monoterpene
      peroxide glycosides, (3S)-3-O-(3',4'-diangeloyl-beta-D-glucopyranosyloxy)-7
      hydroperoxy-3,7-dimethylocta-1,5-diene (1) and (3S)-3-O-(3',4'-diangeloyl-beta-D
      glucopyranosyloxy)-6-hydroperoxy-3,7-dimethylocta-1,7-diene (2), and five known
      compounds, alpha-spinasterol (3), germacra-4(15),5,10(14)-triene-1-beta-ol (4), 7
      methoxy-4(15)-oppositen-1-beta-ol (5), 6alpha-methoxy-4(15)-eudesmane-1beta-ol
      (6) and alpha-spinasterol 3-O-beta-D-glucopyranoside (7). The structures were
      established by chemical and spectroscopic methods.

PMID- 11456103
TI  - Inhibitory effects on HIV-1 protease of tri-p-coumaroylspermidine from Artemisia
      caruifolia and related amides.
AB  - From a methanol extract of Artemisia caruifolia, which showed a moderate
      inhibitory activity on HIV-1 protease in a preliminary screening, N1,N5,N10-tri-p
      coumaroylspermidine and three dicaffeoylquinic acids were isolated. The former
      compound was found to appreciably inhibit HIV-1 protease. Of related amides which
      were chemically synthesized, N1,N5,N10,N14-tetra-p-coumaroylspermine and
      N1,N4,N7,N10,N13-penta-p-coumaroylte-traethylenepentamine inhibited HIV-1
      protease more potently than N1,N5,N10-tri-p-coumaroylspermidine.

PMID- 11456104
TI  - New paeonilactone-A adducts formed by anaerobic incubation of paeoniflorin with
      Lactobacillus brevis in the presence of arylthiols.
AB  - During the course of preparing anticonvulsant paeonimetabolin-I adducts, new
      paeonilactone-A adducts: 9-phenylthiopaeonilactone-A, 9-(o
      tolylthio)paeonilactone-A, 9-(m-tolylthio)paeonilactone-A, 9-(p-tolylthio)
      paeonilactone-A and 9-(2-naphthylthio)paeonilactone-A, were obtained along with
      expected paeonimetabolin-I adducts by anaerobic incubation of paeoniflorin from
      peony roots with Lactobacillus brevis in the presence of the aromatic thiols,
      phenylthiol, o-tolylthiol, m-tolylthiol, p-tolylthiol and 2-naphthylthiol. The
      structures of these compounds were determined by spectroscopic methods including
      two dimensional (2D) NMR.

PMID- 11456105
TI  - Glochiflavanosides A-D: flavanol glucosides from the leaves of Glochidion
      zeylanicum (Gaertn) A. Juss.
AB  - From the leaves of Glochidion zeylanicum collected in Okinawa, four flavanol
      glucosides, named as glochiflavanosides A-D were isolated along with known
      flavone C-glucosides, vitexin and isoorientin. Their structures were elucidated
      by spectroscopic analyses.

PMID- 11456106
TI  - New chroman derivatives from the Japanese liverworts Metacalypogeia cordifolia
      and Cephalozia otaruensis.
AB  - The diethyl ether extract of the Japanese liverwort Metacalypogeia cordifolia
      yielded five new chroman type derivatives in addition to known sesquiterpenoids.
      One of the new chroman derivatives was also isolated from the ether extract of
      another liverwort, Cephalozia otaruensis. Their structures were established by
      extensive two dimensional (2D) NMR techniques and chemical evidence. They were
      shown to be 2,2-dimethyl-7-(3-methyl-2-butenyl)-chroman derivatives. This was the
      first example of the isolation of the chroman-type compounds, although various
      types of aromatic compounds have been isolated from liverworts.

PMID- 11456107
TI  - Diastereomeric diterpenes from Coleus blumei.
AB  - The chloroform extract of the air-dried leaves of Coleus blumei afforded a
      mixture of diastereomers of a new abietane type diterpene whose structures were
      elucidated by extensive one and two dimensional (ID, 2D) NMR and mass
      spectrometry. Acetylation of the mixture afforded a single compound.
      Antimicrobial tests on the diterpene indicate that it is active against Bacillus
      subtilis, Pseudomonas aeruginosa and Candida albicans.

PMID- 11456108
TI  - A novel quinoline alkaloid possessing a 7-benzyl group from the centipede,
      Scolopendra subspinipes.
AB  - The novel quinoline alkaloid scolopendrine was isolated from the centipede,
      Scolopendra subspinipes mutilans L. Koch. The structure was determined to be 2
      hydroxy-7-[(4-hydroxy-3-methoxyphenyl)methyl]-3-methoxy-8-quinolyl sulfate on the
      basis of high-resolution electron-spray ionization mass spectroscopy and two
      dimensional NMR spectral data. Unlike quinoline alkaloids so far reported,
      scolopendrine is unique in having a 7-benzyl moiety in the quinoline ring.

PMID- 11456109
TI  - Possible physiological roles of proteolytic products of actin in neutrophils of
      patients with Behcet's disease.
AB  - A truncated actin with an N-terminus of Met-44 is known to be selectively
      increased in neutrophils of patients with Behcet's disease and to be generated
      proteolytically by PMN-elastase (Yamashita S. et al., Biol. Pharm. Bull., 23, 519
      522 (2000); Biol. Pharm. Bull., 24, 119-122 (2001)). In this study, the functions
      of the N-terminal peptide consisting of Asp-2 to Val-43 of beta-actin (42-merP)
      and the truncated actin with an N-terminus of Met-44 were examined. We first
      confirmed that the 42-merP existed in the patient plasma. The motility of human
      peripheral blood neutrophils and neutrophilic granulocytes differentiated from HL
      60 cells was suppressed by the 42-merP. Furthermore, when neutrophil-like cells
      from HL-60 cells were preincubated with 10 nm 42-merP, migration of the cells
      induced by chemotactic factors such as fMLP and IL-8 was suppressed. The release
      of PMN-elastase, which is a neutrophil granular enzyme that is responsible for
      the production of the 42-merP and truncated actin, was suppressed by pretreating
      the neutrophils with 42-merP before fMLP-stimulation. The truncated actin was
      unable to polymerize in 0.1 M KCl, suggesting that the increase of truncated
      actin damages the reconstitution capacity of actin in neutrophils of the
      patients. These results suggest that the increase of 42-merP and truncated actin
      in patients with Behcet's disease changes functions of neutrophils

PMID- 11456110
TI  - Simultaneous determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in
      human plasma by liquid chromatography-tandem mass spectrometry employing
      derivatization with a Cookson-type reagent.
AB  - A rapid and highly sensitive LC-MS-MS method for simultaneous determination of 25
      hydroxyvitamin D2 125(OH)D21 and 25-hydroxyvitamin D3 125(OH)D3] in human plasma
      has been developed using derivatization with a Cookson-type reagent, 4-12-(6,7
      dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyll-1,2,4-triazoline-3,5-dione
      (DMEQTAD). The derivatization with DMEQTAD significantly improved the ionization
      efficiencies of 25(OH)D2 and 25(OH)D3 with detection limits of 20 and 12.5 fmol
      (8 and 5 pg) per injection, respectively. The method employed two steps of
      solvent extraction but did not require chromatographic purifications for sample
      pretreatment. The determination was carried out by mass chromatography of the
      protonated molecular ions formed by atmospheric pressure chemical ionization
      operating in the positive-ion mode after the derivatization, and 25
      hydroxyvitamin D4 was used as an internal standard. The intra-assay coefficients
      of variation were below 4.02 and 3.24% for 25(OH)D2 and 25(OH)D3, respectively,
      and the analytical recoveries of both compounds were quantitative. Assay
      linearity was obtained in the range of 0.05-1 ng per tube and the determination
      limit was 3 ng/ml for a 20 microl plasma aliquot, for each compound. The
      developed method was applied to plasma samples obtained from volunteers, two of
      whom had received vitamin D2 supplementation, and gave satisfactory results.

PMID- 11456111
TI  - Proteasomes are involved in the constitutive degradation of growth hormone
      receptors.
AB  - In the mouse Ba/F3-hGHR cell line, which stably expresses human growth hormone
      receptors (hGHRs), the hGHRs were rapidly degraded in the absence of the ligand.
      Human growth hormone-binding protein (hGH-BP), a soluble form of hGHR, was
      released from Ba/F3-hGHR cells, but the hGH-BP release was less than 1% of total
      hGHRs in the cells. Therefore, the hGH-BP release does not markedly contribute to
      hGHR degradation in Ba/F3-hGHR cells. The constitutive degradation of hGHRs was
      inhibited by the proteasome inhibitors MG-132 and clasto-lactacystin beta
      lactone, or the vacuolar H+-ATPase inhibitor, bafilomycin A1. hGH-enhanced
      degradation of hGHRs was also inhibited by MG-132. Moreover, MG-132 inhibited the
      internalization of hGHRs as assessed by 125I-hGH binding to the cell surfaces.
      Ubiquitinated hGHRs were detected in the cell lysate and increased by hGH
      treatment. Furthermore, MG-132 accumulated the ubiquitinated hGHRs induced by
      hGH. However, the ratio of ubiquitinated hGHRs to unubiquitinated hGHRs was very
      small, even with treatment involving both hGH and MG-132. In the hGH-untreated
      cells, the ubiquitinated hGHRs were weakly detected. However, the ubiquitination
      of hGHR was not enhanced by MG-132 as a result of immunoblotting. Thus, the
      ubiquitination of hGHR is unlikely to be involved, at least in the constitutive
      degradation. Taken together, both the proteasome pathway and endosome/lysosome
      pathway are involved in the constitutive degradation of hGHRs. Our results also
      suggest that ubiquitination of the hGHR itself is unlikely to be the trigger of
      the proteasome-dependent degradation.

PMID- 11456112
TI  - Mechanism of protection by S-(1,2-dicarboxyethyl)glutathione triester against
      acetaminophen-induced hepatotoxicity in rat hepatocytes.
AB  - Treatment with the triester of S-(1,2-dicarboxyethyl)glutathione (DCE-GS)
      prevented the hepatotoxicity induced by acetaminophen via elevation of the
      glutathione (GSH) level in rat hepatocytes. This elevation of the GSH level in
      rat hepatocytes by DCE-GS triester was dose- and time-dependent (2.1-fold in 24 h
      with 0.5 mm). DCE-GS triester increased the GSH level much more effectively than
      GSH, DCE-GS, and DCE-GS monoester and diester. Furthermore, the activity of y
      glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in GSH
      biosynthesis, was also increased by DCE-GS triester treatment (1.4-fold in 24 h
      with 1.0 mm). In contrast, with a rat liver homogenate, DCE-GS increased the y
      GCS activity, whereas DCE-GS triester had no effect on this activity. These
      results suggested that DCE-GS triester, which is transported into hepatocytes
      much more effectively than DCE-GS and other DCE-GS esters due to its greater
      lipophilicity, was hydrolyzed to DCE-GS, and then the DCE-GS produced increased
      the GSH level via activation of gamma-GCS in rat hepatocytes.

PMID- 11456113
TI  - Effects of selenium deficiency on expression of selenoproteins in bovine arterial
      endothelial cells.
AB  - Damage to the vascular endothelium by reactive oxygen species causes many
      cardiovascular diseases including atherosclerosis. Such damage can be prevented
      by selenium (Se), which is thought to exert its actions mainly through the
      expression of selenoproteins. Se deficiency increased the susceptibility to tert
      butylhydroperoxide (t-BuOOH) and enhanced lipid peroxidation in bovine arterial
      endothelial cells (BAEC). We investigated the effects of Se deficiency on the
      expression of the selenoproteins in BAEC. 75Se metabolic labeling analysis and RT
      PCR analysis revealed that BAEC expressed two glutathione peroxidase (GPx)
      isozymes, cytosolic GPx (cGPx) and phospholipid hydroperoxide GPx (PHGPx), three
      thioredoxin reductase (TrxR) isozymes, TrxR1, TrxR2 and TrxR3, and selenoprotein
      P (SelP). Se deficiency reduced both enzyme activity and mRNA level of cGPx, but
      did not affect those of PHGPx. SelP mRNA level was also reduced by Se deficiency,
      although the extent of reduction was much smaller than that of cGPx mRNA. We
      further found that TrxR activity was also decreased by Se deficiency but none of
      the mRNA levels of TrxR isozymes were reduced. These results indicate that
      vascular endothelial cells express several selenoproteins including cGPx, PHGPx,
      TrxR isozymes and SelP which might play important roles in the defense system
      against oxidative stresses and that the expressions of these selenoproteins are
      differently regulated by Se status.

PMID- 11456114
TI  - Amino acid sequence and characterization of a rice bran ribonuclease.
AB  - A base-nonspecific and acid ribonuclease (RNase Os) belonging to the RNase T2
      family was purified from rice bran to a homogeneous state by SDS-PAGE. The
      primary structure of RNase Os was determined by protein chemistry and molecular
      cloning. The RNase Os was a simple protein and consisted of 205 amino acid
      residues. Its molecular weight was 22578 and its amino acid sequence showed that
      it was most similar to barley RNase among the known RNase T2 family enzymes
      having 157 amino acid residues identical with barley RNase. However, its N
      terminus was blocked by a gamma-pyroglutamyl residue. The optimal pH of RNase Os
      was around 5.5. The base preference at the B1 and B2 site of RNase Os was
      estimated from the rates of hydrolysis of 16 dinucleoside phosphates, to be
      guanine as the case of RNase LE from tomato. RNase Os was successfully expressed
      from yeast cells using the E. coli yeast expression vector pYE-RNAP.

PMID- 11456115
TI  - Relationship between the neuroprotective effect of Na+/H+ exchanger inhibitor SM
      20220 and the timing of its administration in a transient middle cerebral artery
      occlusion model of rats.
AB  - The aim of this study was to determine the relationship between the
      neuroprotective effect of SM-20220 (N(aminoiminomethyl)-1-methyl-1H-indole-2
      carboxamide methanesulfonate) and the timing of its administration in an
      experimental stroke model. Two hours of occlusion followed by 22 h of perfusion
      of the left middle cerebral artery (MCA) was performed by inserting a nylon
      thread into the MCA to occlude it, and pulling the thread to initiate
      reperfusion. Intravenous infusion of SM-20220 for 1 h reduced the infarct volume
      at doses of 0.2-0.8 mg/kg in a dose-dependent manner without causing changes in
      the systemic arterial blood pressure or blood gases, when SM-20220 administration
      was started 1 h after the onset of occlusion. Administration of SM-20220 at a
      dose of 0.4 mg/kg also reduced the edema formation induced by ischemia. In
      contrast, SM-20220 failed to reduce the infarction, even at 1.6 mg/kg, when
      administration was started 2 h after the onset of occlusion. Thus, the
      therapeutic time window of SM-20220 for this transient MCA occlusion model is 1
      h. Daily administration of SM-20220 (0.4 mg/kg) for the 7 d following 1.5 h of
      middle cerebral artery occlusion reduced the infarct volume with statistical
      significance (p<0.05), showing that SM-20220 did not merely delay but prevented
      ischemic damage.

PMID- 11456116
TI  - Social isolation stress impairs the resistance of mice to experimental liver
      metastasis of murine colon 26-L5 carcinoma cells.
AB  - Our previous study has demonstrated that the exposure of male BALB/c mice to
      social isolation stress caused a suppressed immune response and enhanced liver
      metastasis of colon 26-L5 carcinoma cells. To more precisely understand the
      influence of psychosocial factors on the metastatic process, here we have
      investigated the effect of social isolation stress on the vulnerability of the
      host to develop liver metastasis of colon 26-L5 cells, including the time span
      and incidence of metastatic formation, survival time and chemotherapy response.
      Isolation stress decreased the time period required for the metastasis formation
      relative to that in controls. On day 7 after the tumor injection, the 75%
      incidence of tumor metastasis in the stressed mice was 5 times the 15% incidence
      in the unstressed mice. When exposed to the challenge of lower cell numbers
      (0.025, 0.05, 0.1 x 10(4)/mouse) of colon 26-L5 cells, mice subjected to
      isolation stress developed an elevated incidence of metastasis (33.3, 66.6, and
      100%, respectively) as compared with the controls (0, 33.3 and 50%,
      respectively). The survival time following the tumor inoculation was also shorter
      in the stressed mice (21.83 +/- 1.59d) than in the control mice (24.08 +/- 1.68
      d). Furthermore, the response of liver metastasis to chemotherapy consisting of 2
      mg/kg cisplatin (CDDP) was worse in the stressed mice than that in unstressed
      mice. These findings suggested that social isolation stress could significantly
      impair the resistance of mice to the development of metastasis.

PMID- 11456117
TI  - Antioxidant activity of Fraxetin: in vivo and ex vivo parameters in normal
      situation versus induced stress.
AB  - The aim of this paper was to study the influence of Fraxetin (7,8-dihydroxy-6
      methoxv coumarin) treatment in a Drosophila melanogaster experimental model,
      analyzing several parameters in normal situations and instances of induced
      oxidative stress. Fraxetin treatment was introduced at different ages.
      Antigravity capacity and survival parameters were evaluated as in vivo assays,
      and levels of oxidative status, glutathione and lipid peroxidation, as ex vivo
      assays. The stress situation was induced by negative geotaxis, so physical
      exercise enhanced its basal metabolism, generating free radicals, which are
      probably implicated in the molecular damage related to the aging process. In our
      study, all treatment groups demonstrated a beneficial effect on the evaluated
      parameters. So, in vivo Fraxetin protects fruit flies against oxidative stress
      and improves the survival parameters. Moreover, Fraxetin prevents oxidative
      stress by an important increase in antioxidant reserves of GSH, and peroxidative
      damage is preserved by Fraxetin treatments.

PMID- 11456118
TI  - 4-Acetyl-12,13-epoxyl-9-trichothecene-3,15-diol isolated from the fruiting bodies
      of Isariajaponica Yasuda induces apoptosis of human leukemia cells (HL-60).
AB  - The fruiting bodies of Isaria fungi have been traditionally used in Korea to
      treat cancer. An apoptosis-inducing compound, 4-acetyl-12,13-epoxyl-9
      trichothecene-3,15-diol, was isolated from the methanol extract of fruiting
      bodies of Isaria japonica Yasuda by bioassay-guided fractionation. The apoptosis
      of the human leukemia cells (HL-60) by the compound was accessed by propidium
      iodide-staining flow cytometric analysis, and apoptosis-inducing activity at IC50
      concentration (10 nmol/l) was further confirmed by a nuclear morphological
      change, a ladder pattern of internucleosomal DNA fragmentation, and an activation
      of caspase-3.

PMID- 11456119
TI  - Pharmacokinetics of epinastine and a possible mechanism for double peaks in oral
      plasma concentration profiles.
AB  - The pharmacokinetics of epinastine (EPN), an anti-allergic agent, was
      investigated in rats. The plasma concentration-time profile of EPN after
      intravenous (i.v.) administration was triexponential. After oral administration
      of EPN (7.5 and 20 mg/kg), the drug was rapidly absorbed, and Cmax was reached 2
      h after dosing. A minor secondary peak was observed in EPN plasma concentration
      time profiles at both doses. The bioavailability of EPN after oral dosing was 41
      and 40%. The kinetic parameters (T 1/2, AUC and MRT) for unlabeled EPN were much
      smaller than those for 14C-EPN, which has already been reported. The total
      biliary excretion of EPN at a 7.5 mg/kg dose was 15.5% of the dose, but the
      percentage of conjugates in bile was extremely low and about 11% of the total
      biliary excretion. The increase in the plasma concentration in bile duct-linked
      rats after oral administration of EPN (20 mg/kg) was not observed, indicating
      that a secondary increase in drug concentration based on enterohepatic
      circulation was ruled out. When the gastrointestinal (GI)-transit of phenol red
      (PR) after oral administration of EPN (20 mg/kg) was estimated, the GI-transit of
      PR was significantly delayed, and at 3-4 h after dosing half of the PR dose
      reached the jejunum. The remaining EPN in the small intestine after oral
      administration (7.5 mg/kg) reached peak levels 2 h after dosing, but then partly
      increased again at 4 h. As a result, it was clarified that the double peaks
      observed after oral doses are mainly due to the delayed absorption of a part of
      EPN, based on the reduction in gastric motility caused by the drug.

PMID- 11456120
TI  - Passive targeting of doxorubicin with polymer coated liposomes in tumor bearing
      rats.
AB  - The purpose of this study was to reveal the effectiveness of the polymer coated
      liposomes as a carrier of the anticancer drug doxorubicin in intravenous
      administration. The size controlled doxorubicin-loaded liposomes (egg
      phosphatidylcholine : cholesterol = 1:1 in molar ratio) were coated with
      hydrophilic polymers (polyvinyl alcohol; PVA and hydroxypropylmethylcellulose;
      HPMC) having a hydrophobic moiety in the molecules (PVA-R, HPMC-R). The existence
      of a thick polymer layer on the surface of the polymer coated liposomes was
      confirmed by measuring the change in particle size and the amount of polymer on
      the liposomal surface. The polymer coating effects on the tumor accumulation of
      the drug encapsulated in the liposomes were evaluated in Walker rat carcinoma 256
      cell bearing rats. The doxorubicin-loaded liposomes coated with PVA-R and HPMC-R
      showed higher drug accumulation into the tumor site by prolonging the systemic
      circulation in tumor-bearing rats. The targeting efficiency of the polymer coated
      liposomes calculated with the total and tumorous clearance of the drug was ca. 5
      times larger than that of non-coated liposomes. We ascertained that polymers
      having a hydrophobic moiety in the molecule such as PVA-R and HPMC-R are suitable
      materials for modifying the surfaces of the doxorubicin-loaded liposome to
      improve its targeting properties.

PMID- 11456121
TI  - Stereoselectivity and species difference in plasma protein binding of KE-298 and
      its metabolites.
AB  - In vitro protein binding of KE-298 and its plasma metabolites, deacetyl-KE-298 (M
      1) and S-methyl-KE-298 (M-2), was high in rat (>97%), dog (>89%) and human plasma
      (>99%), respectively. Human serum albumin (>93%) was the main protein involved in
      the binding to plasma proteins, while the binding to human serum globulins was
      low (16-33%). The binding of KE-298 and its metabolites in all species of plasma
      was stereoselective. The (+)-(S)-enantiomers of these compounds bound rat, dog
      and human plasma proteins to a greater extent than did the (-)-(R)-enantiomers,
      except that the case of KE-298 was opposite in rat plasma. The stereoselective
      plasma levels of these compounds in rats, dogs, or humans would likely be due to
      stereoselective differences in binding to plasma albumin. The protein binding of
      M-1 in adjuvant-induced arthritis rat plasma was >97%, and the stereoselectivity
      was similar to the case of normal rat plasma. KE-298 and its metabolites
      remarkably displaced [14C]warfarin, which bound on albumin in a solution of
      diluted rat serum albumin. Similarly, there was a displacement of [14C]warfarin
      in solutions of dog and human serum albumin, and concomitantly the displacement
      of [14C]diazepam. [3H]Digitoxin was not displaced by any of the enantiomers in
      each albumin solution. No stereoselectivity was found in displacement by
      enantiomers of the three compounds. These results suggest that stereoselective
      protein binding can be attributed to quantitative differences in binding to
      albumin rather than to the different binding sites.

PMID- 11456122
TI  - Stereoselective pharmacokinetics and pharmacodynamics of verapamil and
      norverapamil in rabbits.
AB  - We have estimated the pharmacokinetic and pharmacodynamic interactions of
      verapamil (VP) enantiomers and also the interaction between VP and its
      metabolite, norverapamil (NVP). ECGs of conscious rabbits were studied to
      determine the pharmacokinetics of VP enantiomers and racemic NVP in relation to
      their prolongation effect on PR intervals, which were used as an index of VP's
      antiarrhythmic effect. Plasma free fractions of VP enantiomers showed constant
      values at concentrations ranging from 0.022 to 1.10 microm. There were no
      interactions between enantiomers or between VP and NVP. The pharmacological
      effect of the S-enantiomer (S-VP), which was determined by linear regression
      analysis, showed it was about 20 times more potent than that of the R-enantiomer
      (R-VP). The effect of racemic VP was the simple sum of those elicited by both
      enantiomers. These relationships were not significantly different between
      intravenous infusion and bolus injection. Simultaneous intravenous infusion of
      NVP had no influence on the PR intervals. In conclusion, we demonstrated that the
      relationship between plasma unbound concentration of VP enantiomers and their
      pharmacological effect was the simple sum of two enantiomers.

PMID- 11456123
TI  - Th1/Th2-Balancing immunomodulating activity of gel-forming (1-->3)-beta-glucans
      from fungi.
AB  - The immunomodulating effects of various gel-forming (1-->3)-beta-glucans,
      grifolan (GRN), SSG, sonifilan (SPG) and alkaline-treated SPG (SPG-OH), on
      balancing helper T cell activity were examined in a murine model. Plasma from
      mice that were injected with GRN or SPG-OH and trinitrophenyl ovalbumin (TNP-OVA)
      contained TNP-specific antibodies of both IgG1 and IgG2a isotypes. Administration
      of SSG and TNP-OVA significantly augmented the synthesis of IgG2a antibodies,
      while the synthesis of IgG1 was reduced. However, SPG did not enhance the
      antibody response. In the culture supernatants of splenocytes obtained from GRN-
      or SPG-OH-administered mice, high levels of IgGI and low levels of IgG2a and IFN
      gamma were detected. In contrast, high levels of IgG2a and IFN gamma and low
      levels of IgGI were detected in the case of administration of SSG. Furthermore,
      it was shown by intracellular cytokine staining that the proportion of IFN
      gamma+CD4+ double-positive cells among the CD4+ cells from mice administered SSG
      was most strongly increased by addition of PMA and A23187. On the other hand, the
      expression of IL-12 p40 mRNA was more markedly elevated in splenocytes after
      combined administration of TNP-OVA plus SSG than after administration of TNP-OVA
      alone. The highest IFN gamma production was observed when adherent cells of mice
      administered TNP-OVA and SSG were cultured with TNP-primed lymphocytes. This
      effect of administration of SSG on IFN-y production was completely inhibited by
      addition of anti-IL-12 mAb. In conclusion, our study showed that beta-glucans
      have various effects on the Th1 or Th2-dependent antibody subclasses, in
      particular, SSG induces the development of Th1 cells via the IL-12 pathway.

PMID- 11456124
TI  - Antitumor beta glucan from the cultured fruit body of Agaricus blazei.
AB  - Agaricus blazei is a medically important mushroom widely eaten and prescribed in
      Japan. Polysaccharide fractions were prepared from cultured A. blazei by repeated
      extraction with hot water (AgHWE), cold NaOH (AgCA), and then hot NaOH (AgHA). By
      chemical, enzymic, and NMR analyses, the primary structures of AgHWE, AgCA, and
      AgHA were mainly composed of 1,6-beta-glucan. Among these fractions, the NaOH
      extracts showed antitumor activity against the solid form of Sarcoma 180 in ICR
      mice. To demonstrate the active component in these fractions, several chemical
      and enzymic treatments were applied. These fractions were found to be i) neutral
      beta-glucan passing DEAE-Sephadex A-25, ii) resistant to periodate oxidation
      (I/B) and subsequent partial acid hydrolysis (I/B/H), iii) resistant to a 1,3
      beta-glucanase, zymolyase, before I/B, but sensitive after I/B/H. In addition,
      after I/B/H treatment of the neutral fraction of AgCAE, a signal around 86 ppm
      attributable to 1,3-beta glucosidic linkage was detectable in the 13C-NMR
      spectrum. These facts strongly suggest that a highly branched 1,3-beta-glucan
      segment forms the active center of the antitumor activity.

PMID- 11456125
TI  - Recovery of purification-associated reduction in antigen-induced histamine
      release from rat peritoneal mast cells.
AB  - Immunoglobulin E (IgE)-dependent histamine release from purified rat peritoneal
      mast cells (PMC) is very low in comparison to that from a non-purified
      preparation (PEC). The reduced histamine release from PMC is recovered or
      potentiated by reconstitution with separated non-mast cells (NMC). In the present
      study, further characterization was undertaken to elucidate the mechanisms
      involved. Sensitized mast cells were recovered from peritoneal cavities of rats,
      and purified by density gradient centrifugation with Percoll. Effects of NMC
      reconstitution, membrane fraction of NMC, NMC incubation supernatant, adhesion
      molecules and extracellular matrix proteins on IgE-dependent histamine release
      from PMC were examined. IgE-dependent histamine release was significantly
      potentiated by NMC reconstitution to PMC. The potentiation was dependent on the
      concentration of NMC reconstituted and reached a plateau after 30 min incubation.
      Increasing concentration of PMC did not affect the histamine release. Membrane
      fraction prepared from NMC also potentiated PMC histamine release in a dose
      dependent manner. The potentiation reached a plateau in 5 min. Furthermore,
      incubation supernatant of NMC potentiated PMC histamine release. Antibodies
      against intercellular adhesion molecule (ICAM)-1, lymphocyte function-associated
      antigen (LFA)-1, very late activation antigen (VLA)-1, VLA-4 and VLA-6, and
      fibronectin did not affect the potentiation of PMC histamine release by NMC
      reconstitution. Fibronectin, laminin and collagen failed to potentiate PMC
      histamine release. These results indicate that the membrane component(s) of NMC
      in the rat peritoneal cavity seems to modulate IgE-dependent histamine release
      from peritoneal mast cells of rats, and that the active molecule(s) may be
      released from NMC. Adhesion molecules such as ICAM-1, LFA-1 and VLA are not
      involved.

PMID- 11456126
TI  - A 10-kda fragment of fibronectin type III domain is a neutrophil chemoattractant
      purified from conditioned medium of rat granulation tissue.
AB  - A neutrophil chemoattractant has been purified from the conditioned medium of
      granulation tissue obtained from carrageenan-induced inflammation in rats. The
      purified chemoattractant was a basic protein with a molecular mass of 10 kDa on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under
      reducing and non-reducing conditions. NH2-terminal amino acid sequence of the
      purified 10-kDa protein was identical with the sequence of rat fibronectin
      starting from the residue Thr585, indicating that the purified 10-kDa
      chemoattractant is a fragment derived from the NH2-terminal type III domain of
      rat fibronectin.

PMID- 11456127
TI  - Inhibitory effects of ethaverine, a homologue of papaverine, on monoamine oxidase
      activity in mouse brain.
AB  - The effects of benzylisoquinoline compounds such as ethaverine, laudanosine, and
      tetrahydropapaverine on monoamine oxidase (MAO, EC 1.4.3.4) activity in mouse
      brain were investigated. Ethaverine showed an inhibition of MAO activity in a
      concentration-dependent manner (57.6% inhibition at 40 microm). Papaverine also
      inhibited MAO activity (38.1% inhibition at 40 microM). However, laudanosine and
      tetrahydropapaverine did not inhibit MAO activity. The IC50 value of ethaverine
      for MAO was 25.5 microm. Ethaverine non-competitively inhibited MAO activity with
      a substrate kynuramine. The Ki value for ethaverine was 11.9 microM. In addition,
      ethaverine proved to preferentially inhibit type B MAO activity in a
      concentration-dependent manner, with an IC50 value of 32.8 microm. These results
      suggest that ethaverine partially contributes to the regulation of catecholamine
      content.

PMID- 11456128
TI  - Rikkunshi-to raises levels of somatostatin and gastrin in human plasma.
AB  - Rikkunshi-to, a traditional Chinese (Kampo) medicine, has been used to treat
      chronic hypofunctions of the gastrointestinal tract. The effects of Rikkunshi-to
      on the plasma levels of gut-regulated peptide (somatostatin, motilin, gastrin,
      and vasoactive intestinal peptide (VIP)) levels were studied in healthy subjects.
      A single oral administration of Rikkunshi-to caused significant increases in
      plasma somatostatin and gastrin levels at 60 to 240 min compared with a placebo
      group. On the other hand, this medicine showed no effects on motilin and VIP
      levels. In conclusion, these results might indicate that the pharmacological
      action of Rikkunshi-to is closely related to changes in somatostatin- and gastrin
      immunoreactive substance levels.

PMID- 11456129
TI  - Ca2+-Dependent caspase activation by gallic acid derivatives.
AB  - Gallic acid (GA) derivatives, 3,4-methylenedioxyphenyl 3,4,5-trihydroxybenzoate
      (GD-1) and S-(3,4-methylenedioxyphenyl)3,4,5-trihydroxythiobenzoate (GD-3), were
      previously reported to induce apoptosis in tumor cells with IC50s of 14.5 microm
      and 3.9 microm, respectively. To elucidate the mechanism by which these gallic
      acid derivatives (GDs) induce apoptosis, we studied whether GD-1 and GD-3 can
      activate caspases. When promyelocytic leukemia HL-60RG cells were treated with GD
      1 and GD-3, poly(ADP-ribose)polymerase (PARP), a substrate of caspase-3, was
      cleaved into 85 kDa of degradative product with increasing incubation time. GA
      also activated PARP cleavage, which was inhibited by catalase, N-acetyl-L
      cysteine (NAC), and intracellular Ca2+ chelator 1,2-bis(2-aminophenoxyethane)
      N,N,N,N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM), in addition
      to a caspase inhibitor, Z-VAD-FMK. Its inhibitory pattern was identical with that
      of hypoxanthine/xanthine oxidase. On the other hand, GD-1- and GD3-induced PARP
      cleavage was not suppressed by catalase or NAC, but by BAPTA-AM. This suggested
      that the GD-elicited signaling pathway is different from GA's. Taken together,
      GDs activated caspase-3 following intracellular Ca2+ elevation independent of
      reactive oxygen species. Thus, it became evident that the signaling pathway
      leading to apoptosis was regulated by GDs in a different manner from GA.

PMID- 11456130
TI  - Antidepressant effects of apocynum venetum leaves in a forced swimming test.
AB  - An extract of the leaves of Apocynum venetum L. (Apocynaceae) markedly shortened
      the immobility time of male rats in a forced swimming test (FST) in a dose range
      of 30-125 mg/kg, indicating a possible antidepressant activity. This effect was
      comparable to that of the tricyclic antidepressant imipramine (20 mg/kg). Neither
      imipramine (20 mg/kg) nor the Apocynum extract in various doses (30, 60, 125
      mg/kg) produced any overt behavioural change or motor dysfunction in the open
      field test. This result confirms the assumption that the antidepressant effect of
      an Apocynum extract in the FST is specific. Further, it can be speculated that
      this effect might be related to hyperoside and isoquercitrin which are major
      flavonoids in the extract.

PMID- 11456131
TI  - Kinetics of intramolecular acyl migration of 1beta-O-acyl glucuronides of (R)-
      and (S)-2-phenylpropionic acids.
AB  - The stereoselective acyl migration of diastereomeric 1beta-O-acyl glucuronides of
      (R)- and (S)-2-phenylpropionic acid [(R)-1PG and (S)-IPG, respectively] in
      phosphate buffer (pH 7.4) at 310K was investigated using HPLC. The disappearance
      of (R)-1PG was faster than that of (S)-1PG according to pseudo first-order
      kinetics. A kinetic model describing the degradation reactions was constructed.
      The rate constant for acyl migration from the 1beta-O-isomer to the 2-O-acyl
      isomer (k12) was about one order magnitude larger than that for hydrolysis from
      1beta-O-acyl isomer to aglycone (k10). The k12 of (R)-IPG (0.377 +/- 0.005 h(-1))
      was about two times larger than that of (S)-IPG (0.184 +/- 0.003 h(-1)). The
      results indicated that the stereoselectivity in the degradation of 1PG was
      apparently governed by the acyl migration from 1-isomer to 2-isomer. The kinetic
      parameters for acyl migration from 1-isomer to 2-isomer were estimated from
      temperature-dependent experiments using the transition state theory. The value of
      the free energy of activation at 310 K for (R)-1PG (99.67 kJ/mol) was smaller
      than that of (S)-IPG (101.60kJ/mol), suggesting that (R)-IPG showed
      thermodynamically higher reactivity in acyl migration than (S)-1PG.

PMID- 11456132
TI  - Extremely high drug-reductase activity based on aldehyde oxidase in monkey liver.
AB  - Drug-reducing ability of monkey liver cytosol was examined in this study. Monkey
      liver cytosol exhibited significant reductase activities toward zonisamide,
      sulindac and imipramine N-oxide in the presence of 2-hydroxypyrimidine or
      benzaldehyde, an electron donor to aldehyde oxidase. These activities were
      abolished by inhibitors of aldehyde oxidase, such as menadione. These reductase
      activities in monkeys were extremely high compared to those in other animals. The
      zonisamide reductase activity of monkey liver cytosol was about 40-fold higher
      than that of the liver microsomes. It appears that the high levels of aldehyde
      oxidase exists in monkey liver, and zonisamide, sulindac and imipramine N-oxide
      are mainly reduced by this enzyme, not by cytochrome P450.

PMID- 11456133
TI  - Thymidine phosphorylase inhibitors with a homophthalimide skeleton.
AB  - Several N-phenylhomophthalimide derivatives were prepared and their inhibitory
      activity on thymidine phosphorylase/ platelet-derived endothelial cell growth
      factor (TP/PD-ECGF) was assessed. Among them, 2-(2,6-diethylphenyl)-7-nitro
      1,2,3,4-tetrahydroisoquinoline-1,3-dione (9) was found to be a more potent
      inhibitor than the classical inhibitor, 5-nitrouracil (1). Lineweaver-Burk plot
      analysis indicated that 9 shows mixed-type competitive inhibition of TP/PD-ECGF,
      while 1 is a competitive inhibitor.

PMID- 11456134
TI  - Fatal atypical mycobacterial infection in a cardiac transplant recipient.
AB  - A 37-year-old female underwent heart transplantation for giant cell myocarditis.
      The patient died within three-and-a-half months of cardiac transplantation.
      Postmortem specimens from the heart and lung showed multiple necrotizing
      granulomas with numerous acid-fast bacilli. Polymerase chain reaction done on
      both the postmortem samples confirmed the presence of atypical mycobacterial
      infection. This fatal case of atypical mycobacteriosis in a cardiac transplant
      patient is reported for its rarity.

PMID- 11456135
TI  - Identification and stabilization of vulnerable atherosclerotic plaques: the role
      of coronary thermography and external heat delivery.

PMID- 11456136
TI  - Aortic dissection into the interatrial septum.

PMID- 11456137
TI  - Can we eradicate rheumatic fever in the 21st century?
AB  - In the latter half of the 20th century, the clinical importance of variation in
      the virulence of strains of GAS has been clearly demonstrated. Although still
      obscure, the pathogenesis of ARF requires immunologically significant infection
      of the throat by virulent GAS strains. These strains contain large hyaluronate
      capsules and large M-protein molecules. The latter contain epitopes cross
      reactive with host tissues, and also contain superantigenic toxic moieties. In
      areas where ARF has become rare, GAS pharyngitis continues to be common but is
      caused predominantly by GAS strains of relatively low virulence. These, however,
      may colonize the throat avidly and stubbornly. Molecularly distinct pyoderma
      strains may cause acute glomerulonephritis, but they are not rheumatogenic even
      though they may secondarily infect the throat. In developing countries with a
      very high incidence of rheumatic heart disease, identification of the prevalent
      rheumatogenic GAS strains and development of a multivalent vaccine against them
      is currently an interesting strategy. Pending vaccine development, intense
      primary and secondary penicillin prophylaxis should continue to be sharply
      focused on populations with the highest prevalence of RHD as such measures may
      often succeed in driving away the most virulent rheumatogenic clones of GAS from
      their midst.

PMID- 11456138
TI  - Rheumatic fever and rheumatic heart disease in India at the turn of the century.

PMID- 11456139
TI  - Cardiology at the crossroads: challenges for India and lessons from the West.

PMID- 11456140
TI  - Absence of association between serum homocysteine levels and coronary artery
      disease in south Indian males.
AB  - BACKGROUND: Asian Indians are reported to have a very high prevalence of
      premature coronary artery disease. However, traditional risk factors do not
      explain this excess of coronary artery disease. Elevated levels of homocysteine
      are reported to be associated with coronary artery disease among Europeans. This
      study looked at the association of serum homocysteine levels with coronary artery
      disease in South Indians. METHODS AND RESULTS: Four groups of patients were
      studied: Group 1 consisted of healthy nondiabetic subjects without coronary
      artery disease (n=18): Group 2 consisted of nondiabetic subjects with coronary
      artery disease (n=21); Group 3 consisted of type 2 diabetic patients without
      coronary artery disease (n=18) and Group 4 consisted of type 2 diabetic patients
      with coronary artery disease (n=20). The mean homocysteine value was 12.4+/-3.4
      micromol/L in Group 1; 12.6+/-4.6 micromol/L in Group 2; 10.1+/-4.4 micromol/L in
      Group 3; and 10.4+/-3.9 micromol/ L in Group 4. There was no significant
      difference in the homocysteine levels between the groups studied. The prevalence
      of hyperhomocysteinemia, defined as a level of 17.1 micromol/L (the 95th
      percentile for serum homocysteine in the control group) was not significantly
      different among the groups. CONCLUSIONS: Elevated serum homocysteine levels are
      not associated with coronary artery disease in South Indian male subjects with or
      without diabetes. However, the results must be interpreted with caution because
      of the small numbers studied.

PMID- 11456141
TI  - Does inhaled nitric oxide improve survival in operated congenital disease with
      severe pulmonary hypertension?
AB  - BACKGROUND: The present study aimed to assess the impact of inhaled nitric oxide
      on survival following correction of congenital heart defects with residual
      pulmonary arterial hypertension. METHODS AND RESULTS: Inhaled nitric oxide was
      utilized for the management of residual pulmonary hypertension in 24 children
      following surgical correction of their underlying heart defects. Their ages
      ranged from 15 days to 14 months (median 5 months). Pulmonary artery hypertension
      was diagnosed either by direct pulmonary artery pressure monitoring or by
      echocardiography. Inhaled nitric oxide was used electively in 22 patients when
      the ratio of the mean pulmonary arterial pressure and mean systemic arterial
      pressure exceeded 0.5. In the remaining 2 patients, nitric oxide was used only to
      manage a pulmonary hypertensive crisis. Inhaled nitric oxide was also used a
      second time in 2 patients who developed delayed pulmonary hypertensive crisis.
      Twenty-two patients showed an initial response to therapy and the pulmonary
      artery pressures dropped significantly. Of the patients on direct pulmonary
      artery pressure monitoring, a pulmonary artery to systemic artery pressure ratio
      below 0.3 on prolonged therapy was associated with a survival ratio of 4/6
      (including 1 neurological death and one reoperation); that between 0.3 and 0.5
      with a survival ratio of 3/4. Three out of four patients with sustained
      echocardiographic and clinical response also survived and were discharged from
      the hospital. All the patients who showed a lack of response to (n=2), tolerance
      to (n=1), or dependence on (n=6) the use of inhaled nitric oxide died. In
      addition, all 5 patients who had a pulmonary hypertensive crisis died, 3 in spite
      of successful resuscitation with nitric oxide. Thus, excluding one neurological
      death and one re-operation, only 9 (41%) out of 22 patients survived.
      CONCLUSIONS: Though inhaled nitric oxide is effective in lowering pulmonary
      pressure, it does not appear to improve the survival rate following repair of
      congenital heart disease in those with associated severe pulmonary hypertension.
      A randomized trial between the use and non-use of inhaled nitric oxide is
      warranted to determine its exact role in influencing survival in patients with
      residual pulmonary hypertension following surgical repair.

PMID- 11456142
TI  - Plasma lipoprotein(a) levels in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary artery hypertension is a common sequelae of a variety of
      cardiac and lung diseases. Pathogenesis of primary and secondary pulmonary artery
      hypertension is still debatable. METHODS AND RESULTS: We studied the serum
      lipoprotein(a) levels in patients with primary (n=27) and secondary (n=19)
      pulmonary artery hypertension (Eisenmenger syndrome). The results were compared
      with age and sex matched controls (n=46). We also studied the frequency of high
      levels of lipoprotein(a) (> 30 mg/dl) in pulmonary artery hypertension. Mean
      lipoprotein(a) levels were significantly higher in the pulmonary artery
      hypertension group compared to age- and sex-matched controls (31.60+/-15.49 mg/dl
      v. 14.66+/-14.7; p=0.0001). All patients were classified into two groups on the
      basis of their lipoprotein(a) levels (<30 mg/dl and >30 mg/dl). There was a
      higher frequency of lipoprotein(a) >30 mg/dl in patients of pulmonary artery
      hypertension v. controls (52% v. 24%; p= <0.001). Younger age, higher functional
      class, more severe congestive heart failure, shorter duration of symptoms. and
      more cases of hemoptysis were observed in the group with lipoprotein(a) >30
      mg/dl. CONCLUSIONS: High lipoprotein(a) may be a marker and be associated with a
      more adverse prognosis in severe pulmonary artery hypertension. Larger
      prospective studies are needed to establish lipoprotein(a) as a risk factor for
      the development of pulmonary artery hypertension.

PMID- 11456143
TI  - Plasma plasminogen activator inhibitor-1 activity in normoglycemic
      hypertriglyceridemic north Asian Indian subjects: a preliminary case-control
      study.
AB  - BACKGROUND: Recent evidence suggests that increased activity of plasma
      plasminogen activator inhibitor-1, an important component of the insulin
      resistance syndrome, plays a crucial role in the pathogenesis of atherosclerosis.
      METHODS AND RESULTS: In this case-control study, relationships between plasma
      plasminogen activator inhibitor-1 activity, serum triglyceride levels and
      hyperinsulinemia were explored in 40 non-diabetic patients with primary
      hypertriglyceridemia (Group 1) and 40 non-diabetic normotriglyceridemic controls
      (Group 2) matched for potential confounders like smoking and physical activity.
      Mean values of fasting serum insulin levels were increased in Group 1 (p>0.05).
      Hyperinsulinemia was observed in 14 (17.5%) individuals in Group 1 and 11 (13.8%)
      individuals in Group 2. Mean plasma plasminogen activator inhibitor-I activity in
      Group 1 (9.8+/-8.4 IU) was higher than in Group 2 (7.0+/-7.7 IU), though the
      difference was not significant (p>0.05). However, when only subjects with
      elevated levels of plasma plasminogen activator inhibitor-1 activity were taken
      into account, mean values were significantly higher in Group 1 (p<0.05). The
      plasma plasminogen activator inhibitor-1 activity was higher in subjects with
      body mass index >25 in both the groups, significantly so in males (p=0.05).
      Hyperinsulinemic subjects with a body mass index >25 and raised serum
      triglyceride levels had higher mean values of plasma plasminogen activator
      inhibitor-1 activity (18.42+/-11.15 IU) than subjects with similar
      characteristics and normal triglyceride levels (14.22+/-8.20 IU, p<0.05).
      CONCLUSIONS: Though in the current study a trend for hyperinsulinemia and high
      plasma plasminogen activator inhibitor-1 activity was observed in
      hypertriglyceridemic subjects, a larger study is needed to achieve significant
      differences and correlations. Obese male subjects, irrespective of their lipid
      profile, are at risk for thrombotic events in view of their significantly higher
      plasma plasminogen activator inhibitor-1 values. Procoagulant tendency is further
      enhanced if hypertriglyceridemia and hyperinsulinemia are added on to obesity.

PMID- 11456144
TI  - Operative outcome and intermediate term follow-up of neonatal Blalock-Taussig
      shunts.
AB  - BACKGROUND: The neonatal age group is considered to be one of the important risk
      factors for perioperative morbidity and mortality as well as poor long-term
      patency following Blalock-Taussig shunts. METHODS AND RESULTS: Out of a total of
      190 patients who underwent Blalock-Taussig shunts in our institute between July
      1998 and July 2000, 20 patients were aged less than 30 days and this neonatal
      cohort was studied retrospectively. The mean age was 18+/-11 days (range: 3-30
      days). The mean weight of the babies was 3.1+/-0.7 kg, the smallest weighed 2.1
      kg. The cardiac anatomy was tetralogy of Fallot with pulmonary atresia in 6,
      pulmonary atresia with intact ventricular septum in 3, tricuspid atresia in 5 and
      complex single ventricle physiology in the rest. All patients were deeply
      cyanotic and preoperative prostaglandin E1 was needed in 10 patients to ensure
      ductal patency and maintain oxygen saturations prior to the shunt operation. The
      mean hilar right and left pulmonary artery sizes were 3.99+/-0.44 mm and 3.69+/
      0.79 mm, respectively. Three patients (15%) had significant stenosis at the site
      of duct insertion. The shunts were accomplished with 3.5 mm
      polytetrafluoroethylene grafts in 7 patients (35%) and 4 mm in the rest. The mean
      duration of mechanical ventilation was 2.0+/-2.83 days, one patient who developed
      bronchopneumonia needed prolonged ventilation for 14 days. The mean intensive
      care unit stay was 4.79+/-2.66 days. The mean hospital stay was 11.7+/-6.4 days.
      Five patients who developed sepsis stayed beyond 14 days. There were 3 deaths
      (immediate post-operative shock and possibly shunt malfunction in 1,
      bronchopneumonia in 1 and late shunt thrombosis at 3 months in 1). Two patients
      had late shunt block, one of those mentioned above and the other at 3 months
      secondary to infective endarteritis of the right pulmonary artery. All these
      infants received 4 mm grafts. All the 3.5 mm grafts were patent at follow-up.
      Seventeen patients were alive and well at follow-up (mean: 9 months, range: 3-21
      months) with a mean resting systemic oxygen saturation of 77% (66%-95%).
      CONCLUSIONS: The overall shunt patency rate after neonatal Blalock-Taussig shunt
      is about 80% on intermediate term follow-up. A smaller graft size (3.5 mm) does
      not appear to be an incremental risk factor for shunt blockade and operative
      mortality.

PMID- 11456145
TI  - Left ventricular pacing through coronary sinus tributaries: initial experience.
AB  - BACKGROUND: Left ventricular pacing is increasingly being used as a part of
      biventricular pacing in congestive heart failure but data on safety, feasibility,
      reliability and lead maturation are sparse. METHODS AND RESULTS: Seventeen
      patients (13 males and 4 females) with persistent symptomatic degenerative
      complete heart block underwent temporary left ventricular pacing by a left
      subclavian puncture through the coronary sinus to its tributaries using a
      unipolar permanent pacing lead connected to an external pulse generator. The left
      ventricular pacing was done for two weeks. Permanent right ventricular apical
      pacing was also done at the same time through a right cephalic vein cut-down or
      subclavian puncture and the pacing rate was kept below that of the initial left
      ventricular pacing rate. Pacing parameters of the left and right ventricles were
      assessed at the time of implantation and at two weeks. Out of 17 patients, left
      ventricular pacing was successful in 11 (67.7%) patients. The time taken for the
      total procedure was 56+/-18.1 min. Lead displacement was noted in one patient
      without loss of pacing. At the time of implant and after two weeks, left
      ventricular pacing threshold, impedance, R wave height and slew rate were not
      different as compared to right ventricular pacing. Holter recording for 24 hours
      revealed regular left ventricular pacing at the end of two weeks in all patients.
      CONCLUSIONS: The present study shows that left ventricular pacing through
      coronary sinus tributaries is feasible and reliable. Acute and subacute
      maturation of left ventricular pacing are similar to right ventricular apical
      pacing.

PMID- 11456146
TI  - Efficacy and safety of carvedilol in infants with dilated cardiomyopathy: a
      preliminary report.
AB  - BACKGROUND: Carvedilol has proven to be beneficial in a majority of adult
      patients with congestive heart failure. Although the experience from adult
      patients may be extrapolated to older children, symptomatic infants remain a
      subset for whom dosage, safety and efficacy need to be established. The purpose
      of this study was to assess whether treatment with carvedilol is efficacious and
      safe for infants with dilated cardiomyopathy who do not show satisfactory
      clinical improvement despite treatment with conventional medications. METHODS AND
      RESULTS: Eight infants with dilated cardiomyopathy (ejection fraction <30%) who
      were symptomatic despite tailored treatment with decongestive medications, were
      enrolled in the study. Echocardiographic findings and heart failure symptom
      scores were analyzed before and after starting carvedilol. Patients were
      hospitalized and monitored for side-effects during up-titration of carvedilol. At
      a follow-up of 4.5+/-2.2 months, patients receiving carvedilol showed a
      significant improvement in the left ventricular ejection fraction (38.5+/-11% v.
      24.4+/-5%), and heart failure symptom score (p<0.05). No adverse events related
      to carvedilol administration occurred. There were no deaths. CONCLUSIONS:
      Carvedilol is well tolerated in infants with dilated cardiomyopathy and there is
      significant improvement in their functional status. Optimal timing of starting
      therapy, dosage and long-term effects need to be investigated with multi
      institutional trials.

PMID- 11456147
TI  - Percutaneous transluminal coronary angioplasty with stenting of anomalous right
      coronary artery originating from left sinus of Valsalva using the Voda guiding
      catheter: a report of two cases.
AB  - Coronary arteries of anomalous origin are uncommon and some forms seem to be
      predisposed to atherosclerosis. We report two cases of successful stent
      implantation in an anomalous right coronary artery originating from the left
      sinus of Valsalva using the Voda guiding catheter.

PMID- 11456148
TI  - Mechanical ventilation in the prone position: a strategy for acute respiratory
      failure after cardiac surgery.
AB  - Ventilation in the prone position, initially introduced in respiratory therapy to
      improve the drainage of secretions, has been used in intensive care to improve
      oxygenation. We report a case of an obese male patient who underwent elective
      coronary artery bypass grafting and had low PaO2 in the postoperative period. The
      PaO2 improved whenever the patient was ventilated in the prone position. On each
      occasion, oxygenation improved without any change in the hemodynamic parameters.
      The PaO2 increased from 57.8 to 249.7 mmHg on the first occasion, from 48.7 to
      194.6 mmHg on the second and 62.5 to 199.7 mmHg on the third at an FIO2 of 1.0.
      The shunt fraction (Qva/Qt) decreased from 43.6% to 7.2% on the first occasion
      and from 46.7% to 12.5% on the second. Ventilation in the prone position can be
      an effective method for improving oxygenation in patients suffering from
      postoperative acute respiratory failure who are not responding to other
      ventilatory strategies.

PMID- 11456149
TI  - "Concertina" effect during angioplasty of tortuous right and left coronary
      arteries and importance of using over-the-wire system: a case report.
AB  - A case wherein "Concertina" effect appeared during angioplasty of both right and
      left coronary arteries is described. Also, the advantages of using an over-the
      wire system in such cases are stressed especially when extreme tortuosity and
      total occlusion are present together.

PMID- 11456150
TI  - Hemangioma of the pericardium: a case report.
AB  - A 52-year-old male presented with dyspnoea on exertion. He was found to have a
      clinically normal cardiac status and a mass lesion in the anterior mediastinum,
      probably arising from the pericardium near the right atrium, as shown by both
      echocardiography and a computerized tomographic scan of the chest. He was
      successfully operated. The histopathology of the mass revealed it to be a
      hemangioma of the pericardium. This is one of the rare tumors of the pericardium
      and only a few cases have been reported in the literature.

PMID- 11456151
TI  - Batista procedure as a bridge to cardiac transplantation.
AB  - A 37-year-old male patient with dilated cardiomyopathy and end-stage heart
      failure underwent Batista procedure. After 6 months, he underwent orthotopic
      heart transplantation. Though he did not survive the procedure, we conclude that
      Batista procedure may serve as a cost-effective biological bridge to cardiac
      transplantation.

PMID- 11456152
TI  - Aortic valve balloon dilatation in a newborn for critical aortic stenosis
      diagnosed during fetal life.
AB  - A young primigravida was diagnosed to have a fetus with critical aortic stenosis
      at 30 weeks' gestation. A decision to follow-up the fetus till term was taken as
      there was no evidence of congestive heart failure. Post-natal retrograde aortic
      valve balloon dilatation was performed 36 hours after birth. There was marked
      improvement in left ventricular function and the baby is doing well at 1-year
      follow-up. The need for accurate assessment of intracardiac anatomy during fetal
      life in critical aortic stenosis and its impact on therapeutic interventions is
      highlighted.

PMID- 11456153
TI  - Coronary sinus diverticulum with a concealed posteroseptal accessory pathway: a
      red herring?
AB  - A 21-year-old male presented with episodes of paroxysmal tachycardia mediated via
      a concealed posteroseptal accessory pathway. He was also found to have a
      diverticulum of the coronary sinus. However, successful radiofrequency ablation
      was achieved only endocardially under the mitral annulus and not within the
      diverticulum.

PMID- 11456154
TI  - Degradation of natural polyphenols by methanogenic consortia enriched from
      digested municipal sludge.
AB  - Using digested municipal sludge as the inoculum and either rutin, quercetin or
      hesperidin as the sole external carbon source. methanogenic consortia were
      enriched which converted various flavonoids at initial concentration of 0.5 3.0mM
      during stationary incubation at 37 degrees C in serum bottles with specific rates
      ranging from 0.025 to 0.073 micromol min(-1) (mg protein)(-1). In the culture
      fluid, several hydroxyaromatic metabolites as well as VFA (acetate, propionate, n
      butyrate) were detected and biogas was formed in the headspace of the test
      bottles. Most of these metabolites were identified. Based on their sequential
      appearance/disappearance in the test cultures it was concluded that following
      initial hydrolysis of the glycosidic bond by cellular enzymes, ring C of the
      flavane skeleton was hydrolytically cleaved yielding an A- and B-ring fission
      product. In case of the flavonol quercetin, phloroglucinol (A-ring) and 3,4
      dihydroxyphenylacetate (B-ring) were identified as the fission products whereas
      the flavanone hesperetin was cleaved with formation of phloroglucinol (A-ring)
      and 3,4-dihydroxyphenylpropionate (B-ring). In pre-adapted subcultures amended
      with either hesperidin or hesperetin, all of the formed hydroxyaromatic
      metabolites disappeared within 100 h of incubation whereas in the culture medium
      of rutin and quercetin degrading consortia m-cresol (3-methylphenol) was formed
      as the ultimate hydroxyaromatic metabolite being detectable in considerable
      amounts even after prolonged incubation.

PMID- 11456155
TI  - Cofermentation of rutin and hesperidin during two-stage anaerobic pre-treatment
      of high-loaded brewery wastewater.
AB  - In a lab-scale two-stage digester (consisting of an acidification and a methane
      reactor) operated continuously with high-loaded brewers wastewater (psiCOD 9.000
      mg1(-1)) as the primary substrate, the cofermentation of two commonly found
      flavonoids (rutin and hesperidin) was studied. At overall hydraulic retention
      times of 48-50 h and organic loading rates in the methane reactor ranging from 8
      to 10 g COD 1R(-1) d(-1) the addition of up to (0.71 g 1R(-1) d(-1) of either
      rutin or hesperidin did not cause adverse effects on the reactor performance, in
      terms of VFA pattern, COD removal efficiency, and specific biogas production. The
      added flavonoid glycosides were rapidly converted in the acidification reactor
      yielding several hydroxyaromatic metabolites. With hesperidin as the cosubstrate,
      all of the formed metabolites were completely removed during passage through the
      methane reactor whereas in case of rutin, substantial amounts of m-cresol and 4
      hydroxyphenylacetate were built up in the medium and remained in the effluent of
      the methane reactor.

PMID- 11456156
TI  - The variation on the mutagenicity of CNP during anaerobic biodegradation.
AB  - The mutagenicity of water, including herbicide CNP, and its time-variation during
      anaerobic biodegradation were studied through Ames assay using strains with or
      without. S9 mix: TA98, TA 100, YG1021, YG1024, YG1026, and YG1029. The bacteria,
      for the anaerobic biodegradation, was obtained from a paddy field, and
      preincubated for a month. The CNP was decomposed in an anaerobic culture
      inoculated with the bacteria, and finally yielded CNP-amino as one of the CNP
      metabolites. About 16% of the initial CNP was transformed into CNP-amino by the
      14th day. The mutagenicities to TA98. YG1024, and YG1029 strains with S9 mix
      increased with cultivating time, the latter two showed the strongest sensitivity
      to CNP-amino. The contribution of CNP to the mutagenicity decreased as the
      chemical decomposed, while the contribution of CNP-amino increased. However, the
      increased mutagenicity was not limited to the contribution of CNP-amino. but also
      to the contribution of other metabolites. The contributions of other CNP
      metabolites were 67% of total mutagenicity to the TA98 strain and 30% to the
      YG1029 strain. These unknown mutagenic metabolites were the indirect frameshift
      mutagens which did not have nitro- and amino-substituents, and the indirect base
      pair mutagens which might possibly have some amino-substituents.

PMID- 11456157
TI  - Naphthenic acids and surrogate naphthenic acids in methanogenic microcosms.
AB  - Naphthenic acids (NAs) are a complex mixture of naturally occurring acyclic and
      cyclic aliphatic carboxylic acids in petroleum. In the Athabasca oil sands. NAs
      have been identified as the largest component of dissolved organic matter in the
      tailings waters from oils sands extraction processes. They are the major
      contributor to the acute toxicity of the fine tailings wastewaters at the oil
      sands extraction plants in northeastern Alberta, Canada. In this study, three
      sources of NAs were studied, including commercially available NAs, those
      extracted from oil sands process-affected waters, and individual naphthenic-like
      surrogate compounds. Analysis by gas chromatography-mass spectrometry
      demonstrated differences between the commercial and extracted NAs. The NAs
      derived from the process-affected waters showed a short-term inhibition of
      methanogenesis from H2 or acetate, but with time the populations resumed methane
      production. It has been postulated that microbial metabolism of the carboxylated
      side chains of NAs would lead to methane production. The two NA mixtures failed
      to stimulate methanogenesis in microcosms that contained either oil sands fine
      tailings or domestic sewage sludge. However, in microcosms with sewage sludge,
      methanogenesis was stimulated by some surrogate NAs including 3
      cyclohexylpropanoic acid at 400-800 mg/L, 5-cyclohexylpentanoic acid at 200 mg/L
      or 6-phenylhexanoic acid at 200 and 400 mg/L. When added at 200 mg/L to
      methanogenic microcosms containing fine tailings, 3-cyclohexylpropanoic and 4
      cyclohexylbutanoic acids produced methane yields that suggested mineralization of
      the side chain and the ring.

PMID- 11456158
TI  - Characterization of raw water for the ozone application measuring ozone
      consumption rate.
AB  - This study was conducted to illustrate an ideal method for characterizing natural
      waters for ozonation processes in drinking water treatment plants. A specific
      instrument designed with the flow injection analysis (FIA) technique enabled us
      to measure accurately the ozone decomposition rate, which was found to consist of
      two stages: the instantaneous ozone consumption stage and the slower ozone decay
      stage. The ozone consumption rate was measured at the initial and secondary
      stages by determining certain parameters called the instantaneous ozone demand
      (ID) and the pseudo first-order decay rate constant (k(c)). Using the OH*-probe,
      the yield of OH* per consumed ozone was also measured to determine its potential
      to produce OH* for the oxidation of micropollutants during the ozonation process.
      The ozone consumption of the ID values was significant in most natural waters,
      and substantial amounts of OH* were found to generate during the instantaneous
      ozone consumption stage. This study also investigated the effects of
      particulates, ozone doses, and sequential ozone injection on ozone decomposition
      kinetics and OH* formation yield.

PMID- 11456159
TI  - Effect of acid and surfactant treatment on activated sludge dewatering and
      settling.
AB  - The effect of pretreating activated sludge with sulfuric acid and surfactant on
      its exocellular polymer(ECP), dewaterability and settleability was investigated.
      It was observed that the centrifugal dewatering efficiency was increased with the
      decrease of sludge pH value, and which was further improved if the surfactant was
      simultaneously applied. However, to the filtration dewatering, the water content
      reached the minimum in the case of pH 2.5, and the additional use of surfactant
      was also favorable. The water content of sludge dewatered with filtration reached
      73.99% when a pH 2.5 and a 0.1 g surfactant were employed, which was reduced by
      around 2% as compared with surfactant unused. Experimental results indicated that
      the sludge sedimentation rate was significantly accelerated under pH 2.5
      condition, and which was increased once more by the utilization of surfactant.
      Further studies revealed that treating activated sludge with sulfuric acid at pH
      2.5 or combined with surfactant was an effective method to remove the polymers
      from sludge surface and induced the decrease of ECP, which resulted in the
      improvement of dewaterability and settleability. This study suggested the
      potentiality of improving activated sludge mechanical dewaterability by the use
      of sulfuric acid to control its pH at 2.5 or together with a surfactant.

PMID- 11456160
TI  - Changes of activity inducing chromosomal aberrations and transformations of
      chlorinated humic acid.
AB  - The change of the toxicity of chlorinated water after chlorine injection was
      examined. For the measurement of toxicity, chromosomal aberration test and
      transforming test were carried out as indexes to initiating activity and to
      promoting activity in the carcinogenesis process, respectively. Activity inducing
      chromosomal aberrations of chlorinated humic acid gradually decreased with time
      after chlorination. In contrast, activity inducing transformations measured by
      the two-stage assay gradually increased. Thus, the toxicity that decreases or
      increases is present in chlorinated water. Furthermore, activity inducing
      transformations measured by the non-two-stage assay gradually decreased. This
      direction of change was reverse to that of activity inducing transformations by
      the two-stage assay and consistent with that of activity inducing chromosomal
      aberrations. It is speculated that the main reason of decreasing activity
      inducing transformations by the non-two-stage assay is because initiating
      activity detected as activity inducing chromosomal aberrations in chlorinated
      water decreases drastically. Directions of changes of total organic halogen and
      carbonyl group were qualitatively consistent with that of activity inducing
      chromosomal aberrations. Directions of changes of chloroform and dichloroacetic
      acid were qualitatively consistent with that of activity inducing transformations
      by the two-stage assay. Findings of this study suggest that further research is
      necessary to compare carcinogenicity of tap water near water purification plant
      and distant tap water.

PMID- 11456161
TI  - Cadmium uptake by floating macrophytes.
AB  - Cd uptake capacity of a group of floating macrophytes (Salvinia herzogii, Pistia
      stratiotes, Hydromistia stolonifera and Eichhornia crassipes) was determined in
      outdoors experiments during the lowest temperature period of the year. Although
      all studied species were highly efficient in the Cd uptake, Pistia stratiotes was
      selected for further research because of its superior performance and its higher
      average relative growth rate. Cadmium% removal by Pistia stratiotes was greater
      in the first 24 h of the experiments (63, 65, 72 and 74% of the added Cd for 1,
      2, 4 and 6 mg Cd 1(-1), respectively). After 31 days of growth, Pistia statiotes
      efficiently removed Cd at the studied concentrations. The macrophyte was able to
      keep its capacity for Cd removal even though some toxicity symptoms appeared at 4
      and 6 mg Cd 1(-1). The greater the initial concentration, the greater Cd
      bioaccumulation rates. The increase of Cd concentration in plant tissues occurred
      especially in roots and was linearly related to the quantity of Cd added. Cd
      sorption by roots is faster than translocation to the plant aerial part and it
      occurs mainly during the first 24h.

PMID- 11456162
TI  - Cadmium adsorption by sediment in a turbulence tank.
AB  - The mechanism sediment motion that affects cadmium (Cd) adsorption on sediment
      particles was studied in a turbulence tank in the presence (and absence) of bed
      mud. The experimental results were verified by a mathematical model for heavy
      metal transport-transformation developed for the turbulence tank. The
      mathematical model includes the equations of water flow, sediment motion, heavy
      metal transport-transformation, heavy-metal reaction kinematics and equations for
      prescribing the initial conditions and boundary conditions for the experiment.
      The model conforms the transport-transformation of heavy-metal pollutants in
      surface waters to following the law of convective-diffusive of common tracers and
      the characteristics of fate and transport of sediment motion. Variations of
      dissolved Cd concentrations and suspended particulate Cd concentrations with time
      and in the water column were measured and computed. The experimental measurements
      correspond with the computed results. Both the experimental measurements and
      computed results show that it takes about 6 h to reach equilibrium condition for
      cadmium adsorption by sediment particles. This is different from the result
      obtained from experiments conducted in continuously stirred tank reactors (or
      batch reactors) in which adsorption equilibrium can be achieved in about 20 min.
      Determination of the model parameters for sediment adsorption-desorption of
      metals in the tank is discussed. The experimental and computed results obtained
      in this study are useful to solve practical engineering problems in surface
      waters.

PMID- 11456163
TI  - Environmental risk assessment of acrylamide and methylolacrylamide from a
      grouting agent used in the tunnel construction of Romeriksporten, Norway.
AB  - Increased focus on the possible evironmental risk associated with large-scale use
      of grouting agents has revealed that leakage of chemicals from grouting
      activities may cause harm to the environment. Chemical grouting agents are used
      to reduce water leakages in e.g. tunnel constructions. The present study focuses
      on monitoring results and environmental risk caused by releases of non
      polymerised monomers during use of the acrylamide-based grouting agent Rhoca-Gil
      (Siprogel). Drainage water from the tunnel Romeriksporten was monitored with
      respect to acrylamide and methylolacrylamide, as leakage of these substances was
      observed earlier in connection with similar constructions where Rhoca-Gil was
      used. Concentrations of acrylamide and methylolacrylamide in the draining water
      showed that these substances leaked out both in connection with the injection of
      Rhoca-Gil and in connection with after-injection using other grouting agents. Gel
      formation studies with Rhoca-Gil showed that a low degree of polymerisation (and
      hence, large leakages of monomers) can be expected if the product is diluted with
      water. Results from investigation of the environmental fate of methylolacrylamide
      showed that this substance is chemically transformed at the high-pH conditions of
      the tunnel. Ecotoxicological testing of the substances and an environmental
      effects assessment for the receiving water (River Alna and the Oslofjord) showed
      that the discharge of acrylamide and methylolacrylamide may have caused effects
      on the aquatic life in the river and in a limited area of the fjord.

PMID- 11456164
TI  - The occurrence of hepatitis A and astroviruses in selected river and dam waters
      in South Africa.
AB  - Over a period of one year (June 1997-May 1998) samples of surface waters, used
      for domestic and recreational purposes, were collected weekly from the same sites
      on the Klip River and Vaal Dam, Gauteng, South Africa. Sensitive and specific
      reverse transcriptase-polymerase chain reaction-oligonucleotide probe assays were
      used to detect HAV and HAstV RNA in concentrates of the water and infectious
      virus in cell cultures infected with the water concentrates. HAV was detected in
      18 (35.3%) of the river and 19 (37.3%) of the dam water samples, often in
      association with the RNA from other enteric viruses. HAstV was detected less
      frequently and was present in 11 (21.6%) of the river and 3 (5.9%) of the dam
      water samples. A seasonal pattern was noted for HAV but not for HAstV. Cell
      culture amplification in a variety of carefully selected cell culture systems
      enhanced the detection of both viruses. Infectious viruses were detected in dam
      water samples where microbiological indicators of faecal pollution were absent or
      within acceptable limits. The presence of these viruses in the dam and river
      water could pose a potential health risk for people using these waters for
      domestic or recreational purposes.

PMID- 11456165
TI  - The storage of acetate under anoxic conditions.
AB  - Till now the role of storage in activated sludge processes under transient
      conditions has been deeply investigated under anaerobic (EBPR processes) or
      aerobic (bulking control) environments. Little attention has been given to the
      role of storage in processes including anoxic environments. Hence, the aim of the
      present work was to investigate the anoxic storage along with other substrate
      removal mechanisms under transient conditions. Several mixed culture were ad hoc
      selected under anoxic environment and periodic feeding (acetate as carbon source)
      at different organic load rate (OLR) and feed length; then their transient
      response to substrate spike was investigated by batch tests under both anoxic and
      aerobic conditions. The relative role of different mechanisms in the substrate
      removal was established on the basis of COD balance assuming that the acetate COD
      removed from the liquid phase could be oxidised for energy needs or recovered
      into solids as poly-3-hydroxybutyric acid (PHB) (storage), other internal
      precursors or intermediates (accumulation) and active biomass (growth, as
      estimated by ammonium uptake). In all tested conditions, growth response was very
      little while PHB storage was prevailing. In some operating conditions, indirect
      evidence of accumulation (in forms still to be identified) was also found. The
      transient response was not affected by the presence of free amino acids, at least
      for the unacclimated mixed culture under observation. Transient response under
      aerobic condition was quite similar to the anoxic one.

PMID- 11456166
TI  - Cationic polymer and clay or metal oxide combinations for natural organic matter
      removal.
AB  - The effect of adding suspended matter in the form of clay or metal oxide when a
      cationic polymer was employed as the primary coagulant was found to be
      beneficial. The solids provide both an adsorbent for natural organic matter (NOM)
      and a nucleating species for precipitating the NOM-polymer complex. Metal oxides
      in conjunction with a cationic polymer were more promising than clay, with
      effectiveness in the order Fe2O3 > Fe3O4 > Al2O3 > MnO2. Magnesium oxide at a
      much lower dose was nearly as effective as ferric oxide, but of course raised the
      pH level significantly. A simpler and more convenient way of having reactive
      solids present was to add alum to form flocs; for one of the waters studied the
      alum dose could be reduced by 67% by adding 1 mg/L of polymer, to give equal or
      better performance than alum alone at the optimum dose.

PMID- 11456167
TI  - Determination of nutrients limiting biofilm formation and the subsequent impact
      on disinfectant decay.
AB  - Understanding the contribution of both organic and inorganic nutrients to biofilm
      development and the subsequent impact of developed biofilms on disinfectant decay
      are important requirements for distribution system management strategies.
      Nutrient limitation may be one way to control biofilm development without
      increasing disinfectant dosing. Little is known, however, of the nutrient
      requirements of biofilms in distribution systems. Indeed, the effects on biofilm
      development due to the addition of nutrients to distribution systems and what
      impact biofilm development may have on disinfectant decay is still poorly
      understood. This study used annular reactors to determine the nutrients limiting
      for biofilm development in drinking water from two different Sydney sources and
      the subsequent effects of biofilm development on disinfectant decay. It was found
      that biofilm development in Sydney water was limited by organic carbon and that
      biofilm development promoted chloramine decay. Moreover, biofilm development
      occurred in the presence of chloramine. The ability of biofilms to respond to
      increases in disinfectant concentrations was dependent on the biomass of the
      biofilms. In a comparative study using chlorinated drinking water containing very
      low levels of organic carbon, biofilm development was not detected. Removal of
      organic carbon resulted in greater persistence of chlorine, which led to greater
      biofilm control. It was also shown that biofilms could contribute cells to the
      aqueous phase. The results of the study indicate that treatment and system
      management strategies should incorporate organic carbon removal to limit biofilm
      development through a combination of retarding bacterial growth and enhancing
      disinfectant persistence.

PMID- 11456168
TI  - Water quality before and after deep tunnel operation in Milwaukee, Wisconsin.
AB  - The mitigative effects of the deep tunnel for temporary storage of storm water
      and sewage, on the water quality of the Milwaukee, Menomonee, and Kinnickinnic
      Rivers are investigated. The analysis is based on data from the Milwaukee
      Metropolitan Sewerage District's overflow and surface-water quality monitoring
      program. Statistical analysis of water quality parameters (BOD, phosphorus,
      suspended solid, fecal coliform counts, zinc, and chloride) in the three rivers
      indicates that Menomonee River benefits the most from the deep tunnel. Fecal
      coliform counts inside the CSO area, and to a certain extent BOD and zinc levels,
      exhibit the most significant decline after 1994 when the tunnel came on line.
      These conclusions are based on t-test comparisons of regional averages
      incorporating spatial and temporal correlations from 1991 to 1993 and 1994 to
      1997. The results from t-tests are complemented and confirmed with results from
      Mann-Kendall tests for trend. Suspended solids and chloride do not decrease after
      1994.

PMID- 11456169
TI  - Simultaneous storage and degradation of PHB and glycogen in activated sludge
      cultures.
AB  - Bacteria in activated sludge are subjected to periods of substrate availability
      and absence of external substrates. The response of bacteria to such dynamic
      conditions was studied in a 2 L sequencing batch reactor (SBR) by subjecting a
      mixed microbial population to successive periods of external substrate
      availability (feast period) and no external substrate availability (famine
      period). In previous studies, acetate or glucose was used as single substrate
      leading to the storage of polyhydroxybutyrate or glycogen, respectively. In this
      study, a mixture of acetate and glucose was used. It appeared that both
      substrates were consumed simultaneously. The relative contribution of growth and
      storage processes was in these experiments similar as in the systems fed with a
      single substrate only. The ratio of substrate uptake over substrate storage was
      0.6 Cmol/Cmol for both substrates. The uptake rate of acetate was not influenced
      by the simultaneous uptake of glucose. The degradation kinetics and rates of the
      storage compounds were the same as for the systems in which only one compound was
      stored in the activated sludge. The global performance of the culture grown on
      mixed substrates could therefore be described as the sum of the conversions
      observed in cultures fed with the individual substrates.

PMID- 11456170
TI  - Nutrient addition to enhance biological treatment of greywater.
AB  - This study compares the chemical oxygen demand (COD) removal and respiration
      rates of a microbial population treating real and synthetic greywaters dosed with
      nutrient supplements. The nutrient composition of the real and synthetic
      greywaters was analysed and the dosing regime for nitrogen, phosphorus and a
      range of trace metals planned accordingly. The doses consisted of eight single
      additives (macronutrients and trace metals) to the control greywater and six
      trace metal additions to C: N : P balanced greywater. The COD removal for the
      control real and synthetic greywater in lab-scale activated sludge systems (0.038
      and 0.286 kg COD kg MLSS(-1) d(-1), respectively) confirmed nutrient limitation
      and the poor degree of greywater treatment. Nutrient dosing increased the COD
      removal rate and oxygen uptake rate in many cases. The greatest stimulation of
      microbial activity was observed with zinc additions to C: N: P balanced real
      greywater (1.291 kg COD kg MLSS(-1) d(-1) over 30 times the control). Inhibitory
      effects to various extents were rare and limited mainly to the additions of
      metals to synthetic greywater. The dominance of chemicals effects was observed on
      addition of some micronutrients; notably iron and aluminium, metals on which many
      coagulants for use in biotreatment of other wastewaters are based. The data
      indicate that the impact of understanding microbial processes and the nutrients
      required for wastewater treatment can only serve to optimise process efficiency
      for the proposed treatment of greywater.

PMID- 11456171
TI  - Metabolic modelling of full-scale biological nitrogen and phosphorus removing
      wwtp's.
AB  - This paper evaluates the experiences with modelling full-scale biological
      phosphorus and nitrogen removing wastewater treatment plants. For the simulation,
      we used a metabolic phosphorus model integrated in ASM2d, further referred to as
      TUDP-model. It was found that the metabolic model for bio-P removal can be
      applied for modelling full-scale wwtp's, without extensive parameter adjustments.
      A stepwise modelling approach was proposed. Only three specific parameters were
      calibrated. Two parameters, the inert fraction in the influent and the actual
      anoxic sludge fraction will need calibration for all systems. Parameter
      sensitivity analyses showed that the sensitivity of operational data, often
      considered as known input data, is high. The model kinetics were found less
      sensitive. This will in general be the case for all low-loaded wwtp's recorded in
      their pseudo-steady state. Based on mass balance calculations, operational data
      and measurements were evaluated. Since all terms on a phosphorus balance can be
      measured, errors in operational data (e.g. SRT and flow rates) become very
      apparent in P-removal models (ASM2d, TUDP). We suggest using the P-balance in
      general for wwtp modelling, as a check on data consistency. This study showed
      that considering operational data per definition as known input data is not
      justified. Therefore, operational data should be evaluated, or considered in
      model calibration over the use of kinetic and stoichiometric parameters.

PMID- 11456172
TI  - Role of anions on heavy metal sorption of a cellulose modified with poly(glycidyl
      methacrylate) and polyethyleneimine.
AB  - The influence of anions on the equilibrium and kinetic uptake of heavy metals
      from an aqueous solution by a novel nitrogen-type chelating adsorbent was
      evaluated. Equilibrium experiments revealed that stoichiometric amounts of metals
      and anions are adsorbed by the resin. Kinetic studies showed that during the
      initial stage of adsorption, the anions are adsorbed by the adsorbent prior to
      the metal ions. This occurred almost simultaneously with an increase in solution
      pH. At equilibrium, the pH returned towards its initial value. The concentration
      of anion also fluctuated during the entire equilibration process. Following these
      observations, mechanisms governing the role of anions on enhancing capacity and
      rate of metal uptake of this type of chelating adsorbent type were established.

PMID- 11456173
TI  - In situ analysis of Nitrosomonas spp. in wastewater treatment wetland biofilms.
AB  - The presence of the ammonia-oxidising group Nitrosomonas in developing biofilms
      from a subsurface flow dairy effluent treatment wetland was investigated using in
      situ hybridisation and a crude semi-quantitative PCR. Fluorescently labelled
      oligonucleotide probes, specific for the Nitrosomonas europaea and Nitrosomonas
      eutropha species, showed that nitrifying bacteria were present from the onset of
      biofilm development but that over a five month period the proportions remained
      low (averaging less than 1% of the total bacterial population). The greatest
      presence of these nitrifiers was found in the second trench of the subsurface
      flow wetland. Nitrosomonas were also found to be susceptible to environmental
      change; adverse environmental conditions, such as low temperatures, coincided
      with negligible Nitrosomonas presence throughout the wetland. However, during one
      period of elevated ammonium concentrations Nitrosomonas presence rapidly
      increased as high as 7% of the total bacterial population. Investigations of
      relative occurrence of effluent bacterial population of Nitrosomonas europaea and
      the biofilm populations showed that Nitrosomonas presence in the effluent
      coincided with significant presence in adjacent biofilms. This suggests seeding
      between both sessile and planktonic populations of this species. Nitrosomonas
      occurred as single cells in biofilms throughout the study and were never observed
      as dense clusters.

PMID- 11456174
TI  - The regeneration of field-spent granular-activated carbons.
AB  - The thermal regeneration of field-spent granular-activated carbons (GAC) is being
      increasingly adopted as a cost-effective alternative to disposal. The success of
      this practice requires the adjustment of process conditions to maximise the
      recovery of the original carbon characteristics while minimising carbon loss.
      This paper describes an investigation into the regeneration of several field
      spent GAC representative of those typically generated by the drinking water
      treatment industry. The carbons were initially investigated for their ash
      contents and inorganic compositions in order to determine the accumulation of
      metallic species that affect the regeneration process. Regeneration was conducted
      in steam at 800 degrees C over reaction times between 0 and 60 min in order to
      achieve different degrees of carbon gasification. Weight losses were determined
      for each condition and the resulting carbons characterised for their apparent
      density, porosity, surface area and aqueous adsorption characteristics. Results
      showed that spent carbons recovered most of their adsorption characteristics when
      heated to 800 degrees C under inert conditions. Steam gasification in the range
      of 5-10 wt% burn-off had some positive effects on the characteristics of the
      spent carbons which were in most cases counteracted by a reduction in the carbon
      yield. Steam gasification in excess of 15 wt% burn-off caused a rapid increase in
      the carbon mesoporosity but a significant deterioration in the carbon
      microporosity, BET surface area and adsorption capacity for organic species of
      small molecular size.

PMID- 11456175
TI  - Study of dissolved silicon and nitrate dynamics in a freshwater stream.
AB  - Dissolved reactive silicon and nitrate were measured at weekly intervals over a 3
      year period (1991-94) on a 1.2km reach of a gauged Dorset Mill Stream. In
      addition, dissolved nitrite was measured over a 8 month period from the spring to
      late autumn in 1992. Two intensive studies with sampling at 2h intervals were
      also completed in low and high riverflow conditions. The results were analysed
      using a mass-balance approach with the loss and gains in nutrients dissolved in
      the water expressed in terms of areal rates. Losses of both nutrients occurred
      during periods of low streamflow in spring and summer. Losses of silicon are
      attributed to growth of epilithic diatoms whereas nitrate losses are consistent
      with a number of processes including the growth of aquatic plants, the
      development of epilithic biofilms and nitrogen transformations, such as
      denitrification, in bed-sediments. Stream water gained dissolved nitrite during
      its passage through the section. Silicon losses from the stream amounted to
      between 52 and 63 mmol m(-2) d(-1) (expressed per area of bed-sediment) for the
      spring periods in 1992-94. Nitrate losses were more variable with overall rates
      between 24 and 89 mmol m(-2) d(-1) for the summer periods in 1991-93.

PMID- 11456176
TI  - A biochemical hypothesis explaining the response of enhanced biological
      phosphorus removal biomass to organic substrates.
AB  - Anaerobic/aerobic batch experiments were conducted with a variety of volatile
      fatty (VFAs) and amino acids on two sequencing batch reactor populations
      displaying enhanced biological phosphorus removal. The batch experiments were
      consistent between the two systems and with the past literature: acetic and
      isovaleric acid were the most efficient substrates, and propionic acid was the
      least efficient of the 2-5 carbon VFAs (lack of acclimation was ruled out). A
      survey of the engineering and biochemical literature revealed that both acetic
      and isovaleric acid resulted in a negative reaction redox balance (i.e. it
      requires reducing equivalents such as NADH2) during their biotransformation to
      polyhydroxyalkanoates (PHAs). In addition, the survey indicated that acetic and
      isovaleric acid resulted in 3HB rather than 3HV or 3H2MV formation. Two possible
      hypotheses were put forward for evaluation: (1) it was hypothesized that a
      negative intracellular redox balance might result in higher PHA content since PHA
      biosynthesis could be sustained under anaerobic conditions (no NADH2 build up),
      and/or (2) it was hypothesized that 3HB resulted in greater P-uptake than other
      PHA forms such as 3HV.

PMID- 11456177
TI  - Sequential erosion/deposition experiments--demonstrating the effects of
      depositional history on sediment erosion.
AB  - Experiments on the erosion of a bed of kaolinite were carried out in a rotating
      circular flume. Each experiment was carried out using the stratified bed which
      resulted from the previous experiment. Changes in suspended sediment
      concentrations during the experiments were explained by the history of the
      deposition. The sequence of experiments showed how the rate of erosion and the
      amount eroded reflected the structure of the bed and that of the individual flocs
      which created it. Results suggest that modelling of sediment/contaminant
      transport needs to account for the manner in which deposition took place.

PMID- 11456178
TI  - Application of the 15N technique to determine the contributions of nitrification
      and denitrification to the flux of nitrous oxide from aerated pig slurry.
AB  - In order to elucidate and quantify nitrogen transformations occurring during
      aerobic treatment of pig slurry, two laboratory experiments were carried out with
      contrasting levels of aeration, high level (experiment 1) and low level
      (experiment 2) of aeration. During these experiments, after reaching steady-state
      conditions, a single pulse of NO3(-)-15N tracer was added directly to the
      reactor. When nitrification conditions were prevailing (experiment 1), no
      transformation of added NO3(-)-15N occurred (98.7% 15N-recovery as nitrates in
      the liquid slurry). Moreover, the unlabelled nitrous oxide (N2O) measured (7.4%
      of the total nitrogen content of the raw slurry) strongly demonstrated that the
      source of N2O emitted was nitrification. During simultaneous nitrification and
      denitrification conditions (experiment 2), the added NO3(-)-15N was found in
      gaseous nitrogen forms (N2O-15N: 27%; N2-15N: 18%) and in the liquid (TN-15N:
      54%). From this result, it was evident that N2O was mainly emitted by
      denitrification process. Using the decrease of the isotopic excess of the NO3(-)
      15N we calculated that 92% of NO2(-)-N was directly denitrified (as gaseous
      forms) without any previous oxidation to nitrate.

PMID- 11456179
TI  - Evaluation and optimization of a reusable hollow fiber ultrafilter as a first
      step in concentrating Cryptosporidium parvum oocysts from water.
AB  - Experiments with a small-scale hollow fiber ultrafiltration system (50,000 MWCO)
      was used to characterize the filtration process and identify conditions that
      optimize the recovery of Cryptosporidium parvum oocysts from 2 L samples of
      water. Seeded experiments were conducted using deionized water as well as four
      environmental water sources (tap, ground, Arkansas river, and Rio Grande river; 0
      30.9NTU). Optimal and consistent recovery of spiked oocysts was observed (68
      81%), when the membrane was sanitized with a 10% sodium dodecyl sulfate (SDS)
      solution and then blocked with 5% fetal bovine serum (FBS).

PMID- 11456180
TI  - Use of similarity measures for quality control of benthic diatom samples.
AB  - A method for evaluating the similarity of replicate benthic diatom samples based
      on the Bray-Curtis similarity measure is described. This technique may be useful
      as part of quality control procedures where objective performance measures are
      required. Levels of similarity > 60% typically indicate good agreement between
      the primary analyst and auditor. However, an evaluation of 57 comparisons
      indicated that achievable levels of similarity were dependent upon the species
      diversity of the sample, with samples with high species diversity typically
      having lower levels of similarity than samples with low species diversity. Whilst
      a threshold value of 60% is adequate for most samples, a stiffer threshold of 70%
      should be applied to samples with very low levels of diversity.

PMID- 11456181
TI  - Effect of pH on the reduction of nitrite in water by metallic iron.
AB  - Chemical reduction is an alternative technique to remove nitrogen oxides from
      contaminated groundwater and closed-surface water body. Metallic iron was
      employed as a reductant for the reduction of nitrite in water in this study. The
      effect of pH on the rate and products of nitrite reduction was investigated with
      a fixed dosage of metallic iron powder (12 mol-Fe/mol-N, size of the powder: 80
      mesh). The reduction of nitrite by metallic iron was a pseudo-zero-order reaction
      under the experimental conditions. The reduction rate of nitrite was increased
      with decreasing the pH of reaction solution, and the pseudo-zero-order reaction
      rate constants were 180, 130, 60, 15, 10, and 1 mM/h at pH = 2, 3, 4, 5, 6, and
      7, respectively. The reduction products of nitrite were nitrogen gas and
      ammonium. The yields of nitrogen gas from nitrite reduction were 0.63, 0.74,
      0.81, 0.87, 0.92, and 0.98 as molar ratios of nitrogen atom at pH =2, 3, 4, 5, 6,
      and 7, respectively. Neutral condition enhanced the formation of nitrogen gas
      from nitrite reduction.

PMID- 11456182
TI  - Effect of nitrate exposure history on the oxygen/nitrate diauxic growth of
      Pseudomonas denitrificans.
AB  - Pseudomonas denitrificans pre-cultured (revived from agar plates) under varying
      conditions (nitrate absent or present; dissolved oxygen absent or present) was
      subsequently grown aerobically with or without nitrate present, and finally
      exposed to anoxic conditions (i.e., aeration stopped and dissolved oxygen
      stripped from solution). The occurrence and length of diauxic lags following
      transition from aerobic to anoxic conditions were affected strongly by the
      nitrate and oxygen exposure history of the biomass.

PMID- 11456183
TI  - Evaluation of dioxin contamination in sewage sludge discharges on coastal
      sediments from Catalonia, Spain.
AB  - The fate of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)
      in sewage sludges after discharge into the sea was investigated. Sediment samples
      were analysed at a sewage sludge disposal site as well as in the surrounding
      areas. Moreover, eight sediment samples from two rivers in Catalonia and three
      sediment samples from Catalonian Coast were analysed to determine the background
      levels of contamination. Total international toxicity equivalent (I-TEQ) values
      for these sediments ranged from 0.42 to 8.01 pg g, with a mean value of 4.15 pg/g
      and a median value of 3.69 pg/g. However, the I-TEQ values of sludge-treated
      areas were higher: 57.04 pg/g at the dumping site, and within a range of 13.42
      47.76 pg/g near this site. Thus, European sediment quality objectives were
      exceeded. The higher concentrations coincided with changes in the ratio between
      PCDD and PCDF levels, suggesting the influence of the sewage sludge on coastal
      sediments.

PMID- 11456184
TI  - Optimizing detection of heat-injured Listeria monocytogenes in pasteurized milk.
AB  - Optimal conditions for the detection of heat-injured cells of Listeria
      monocytogenes in modified Pennsylvania State University (mPSU) broth were
      determined using a response surface design generated by a computer program,
      EChip. Different combinations of incubation temperatures and lithium, magnesium,
      and D-serine concentrations were evaluated to determine the optimum conditions
      for the detection of heat-injured L. monocytogenes in filter-sterilized whole
      milk inoculated with selected problematic background microflora. A concentration
      of 212 mM lithium chloride completely inhibited the growth of Enterococcus
      faecium while permitting recovery and detection of L. monocytogenes. A
      concentration of 15.8 mM MgSO4 was found to be optimum for the recovery and
      detection of L. monocytogenes. A concentration of 140.2 mM D-serine was found to
      completely inhibit the germination of Bacillus subtilis var. globii spores but
      not recovery and detection of L. monocytogenes. Under optimum concentrations of
      LiCl, MgSO4, and D-serine and in the absence of background microflora, the effect
      of incubation temperature on percentage detection was described by a second-order
      polynomial model, and 28 degrees C was determined to be optimal. In the presence
      of background microflora, the effect of incubation temperature on percentage
      detection of heat-injured cells was described by a third-order polynomial model,
      and 30 degrees C was found to be optimal. Optimizing the levels of highly
      specific and selective agents, nutrients, and incubation temperature in one
      recovery enrichment system dramatically increased the Listeria/background
      microflora ratio. This resulting medium, optimized PSU (oPSU) broth, greatly
      improved the detection of heat-injured and nonheat-injured L. monocytogenes by
      both conventional and molecular methods (Oxoid's Listeria Rapid Test, Gen-Probe's
      Accuprobe Listeria monocytogenes Culture Identification Test, and Qualicon's BAX
      for screening Listeria monocytogenes).

PMID- 11456185
TI  - Influence of food matrix on inactivation of Bacillus cereus by combinations of
      nisin, pulsed electric field treatment, and carvacrol.
AB  - Carvacrol was used as a third preservative factor to enhance further the synergy
      between nisin and pulsed electric field (PEF) treatment against vegetative cells
      of Bacillus cereus. When applied simultaneously with nisin (0.04 microg/ml),
      carvacrol (0.5 mM) enhanced the synergy found between nisin and PEF treatment
      (16.7 kV/cm, 30 pulses) in potassium-N-2-hydroxyethylpiperazine-N-ethanesulfonic
      acid (HEPES) buffer. The influence of food ingredients on bactericidal activity
      was tested using skimmed milk that was diluted to 20% with sterile demineralized
      water. The efficacy of PEF treatment was not affected by the presence of
      proteins, and results found in HEPES buffer correlated well with results in milk
      (20%). Nisin showed less activity against B. cereus in milk. Carvacrol was not
      able to enhance the synergy between nisin and PEF treatment in milk, unless used
      in high concentrations (1.2 mM). This concentration in itself did not influence
      the viable count. Carvacrol did act synergistically with PEF treatment in milk,
      however not in HEPES buffer. This synergy was not influenced by proteins in milk,
      as 5% milk still allows synergy between carvacrol and PEF treatment to the same
      extent as 20% milk.

PMID- 11456186
TI  - Antimicrobial activity of essential oils from plants against selected pathogenic
      and saprophytic microorganisms.
AB  - The beneficial health effects of extracts from many types of plants that are used
      as seasoning agents in foods and beverages have been claimed for centuries. The
      purpose of this study was to examine the effectiveness of selected herb and spice
      essential oils for control of growth and survival of microorganisms. Inhibition
      of growth was tested by the paper disc agar diffusion method. Antibiotic
      susceptibility discs were used as control. Minimum lethal concentration (MLC) was
      determined by the tube dilution method. Essential oils from anise, angelica,
      basil, carrot, celery, cardamom, coriander, dill weed, fennel, oregano, parsley,
      and rosemary were evaluated. Inhibition ranged from complete with oregano to no
      inhibition with carrot oil for each of the test strains that included: Listeria
      monocytogenes, Staphylococcus aureus, Escherichia coli O:157:H7, Yersinia
      enterocolitica, Pseudomonas aeruginosa, Lactobacillus plantarum, Aspergillus
      niger, Geotrichum, and Rhodotorula. Oregano essential oil showed the greatest
      inhibition (zone, > or = 70 to 80 mm) (MLC, approximately 8 ppm). Coriander and
      basil were also highly inhibitory (MLC, approximately 25 to 50 ppm) to E. coli
      O:157:H7 and to the other bacteria and fungi tested. Anise oil was not
      particularly inhibitory to bacteria (inhibition zone, approximately 25 mm);
      however, anise oil was highly inhibitory to molds. Because some of the herbal and
      spice essential oils are highly inhibitory to selected pathogenic and spoilage
      microorganisms, they may provide alternatives and supplements to conventional
      antimicrobial additives in foods.

PMID- 11456187
TI  - Fungitoxic activity of 12 essential oils against four postharvest citrus
      pathogens: chemical analysis of thymus capitatus oil and its effect in
      subatmospheric pressure conditions.
AB  - The fungitoxic activity against Penicillium digitatum, Penicillium italicum,
      Botrytis cinerea, and Alternaria citri of 12 essential oils (EOs) distilled from
      medicinal plants is reported. The results of the in vitro trials show strong
      fungitoxic activity of Thymus capitatus (L.) Hofmgg EOs, which inhibited the
      growth of the four fungi at a concentration of 250 ppm (vol/vol). The other 11
      essences reduced the development of the fungi from 95 to 9% at 250 ppm (vol/vol).
      The fungitoxic activity of T. capitatus EOs (75, 150, and 250 ppm) on healthy
      orange fruits, inoculated with P. digitatum (10(8) conidia ml(-1)) by spraying
      and placed in 10-liter desiccators, was weak at atmospheric pressure (3 to 10%
      inhibition at all three concentrations), while in vacuum conditions (0.5 bar),
      conidial mortality on the exocarp was high (90 to 97% at all three
      concentrations). These data proved not to be statistically different from
      treatments with thiabendazole-TBZ (2,000 ppm). Scanning electron microscope
      observations showed that T. capitatus EO vapors altered the morphology of P.
      digitatum hyphae and conidia. The gas-chromatographic analyses of thyme EO
      indicated that carvacrol was present at 81 to 83%, p-cymene at 4.5 to 5%, gamma
      terpinene at 2.6 to 3.3%, caryophyllene at 1.5 to 1.6%, beta-myrcene at 1.6%, and
      linalool at 1.1 to 1.2%. Carvacrol proved to be the most important fungitoxic
      compound among the thyme EO constituents, but, unlike thyme EO, it caused
      alterations to the fruit at the concentration of 75 ppm.

PMID- 11456188
TI  - Nannocystis exedens: a potential biocompetitive agent against Aspergillus flavus
      and Aspergillus parasiticus.
AB  - This study examined the potential for controlling toxigenic Aspergillus flavus
      and Aspergillus parasiticus by biological means using a myxobacterium commonly
      found in soil. The ability of Nannocystis exedens to antagonize A. flavus ATCC
      16875, A. flavus ATCC 26946, and A. parasiticus NRRL 3145 was discovered.
      Cultures of aflatoxigenic fungi were grown on 0.3% Trypticase peptone yeast
      extract agar for 14 days at 28 degrees C. When N. exedens was grown in close
      proximity with an aflatoxigenic mold, zones of inhibition (10 to 20 mm) developed
      between the bacterium and mold colony. A flattening of the mold colony on the
      sides nearest N. exedens and general stunting of growth of the mold colony were
      also observed. When N. exedens was added to the center of the cross-streak of a
      mold colony, lysis of the colony by the bacterium was observed after 24 h.
      Microscopic observations revealed that N. exedens grew on spores, germinating
      spores, hyphae, and sclerotia of the molds. These results indicate that N.
      exedens may be a potential biocontrol agent against A. flavus and A. parasiticus.

PMID- 11456189
TI  - Source and identification of histamine-producing bacteria from fresh and
      temperature-abused albacore.
AB  - Histamine-producing bacteria were isolated from fresh and temperature-abused
      albacore using two different isolation procedures. Typically, the bacterial
      isolates on Niven's or modified Niven's medium produced negligible or low levels
      of histamine (<300 ppm) in histamine enumeration broth. The most frequently found
      species using this approach was Hafnia alvei. By prescreening on selective media
      (eosin methylene blue [EMB] agar for enteric bacteria; deMan Rogosa Sharpe agar
      for lactic acid bacteria: KF streptococcus agar for streptococci; pseudomonas
      isolation [PI] agar for pseudomonads; and staphylococcus medium 110 agar for
      staphylococci) prior to plating on histidine decarboxylase differential media,
      detection rate of true histamine formers increased. Prolific histamine producers
      capable of forming >1,000 ppm histamine in culture broth were isolated when PI
      and EMB agars were used for prescreening. Among the selective media tested, EMB
      agar was most effective in selecting high histamine producers, as demonstrated by
      the highest rate of true positives based on histamine analysis. Histamine
      producing isolates were mostly enteric bacteria, including Morganella morganii,
      H. alvei, Klebsiella spp., Citrobacter freundii, Enterobacter spp., and Serratia
      spp. M. morganii isolated on PI agar from temperature-abused albacore muscle was
      found to be the highest histamine former. This species was not isolated from
      fresh albacore. while other enteric bacteria were frequently detected on the
      gills. However, only a few species isolated from both fresh and temperature
      abused muscles were identified as high histamine formers.

PMID- 11456190
TI  - Formation of biogenic amines in bulk-stored chilled hake (Merluccius merluccius
      L.) packed under atmospheres.
AB  - The production of biogenic amines in the lots of whole hake stored bulk under a
      controlled or modified atmosphere for 12 days with the gas mixture 40% CO2:40%
      O2:20% N2 and after packing in trays under a modified atmosphere in the same
      mixture of gases or with air was studied. Results indicated a close relation
      between the development of trimethylamine nitrogen (TMA-N) and the sensory
      parameters gill appearance and odor but not with the general appearance of the
      skin and eyes. These results were related to changes observed in the
      concentration of gases (CO2 and O2) during storage containers and trays. The lot
      of bulk-stored whole hake in controlled atmospheres for 12 days with the gas
      mixture 40% CO2:40% O2:20% N2 and then packed in trays with the same atmosphere
      exhibited TMA-N levels below the 12.5 mg/100 g limit designated by the
      legislation in force (Directive 91/143/EU) on day 31 of storage when the sensory
      parameters general appearance and skin and gill color were not rejected.
      Histamine and tyramine levels were less than 1 mg/kg, putrescine levels were
      approximately 7 mg/kg, and cadaverine and agmatine levels were 33.91 and 20.33
      mg/100 g, respectively.

PMID- 11456191
TI  - Development and assessment of an intelligent shelf life decision system for
      quality optimization of the food chill chain.
AB  - The principles of application of a Shelf Life Decision System (SLDS) for the
      optimization of the distribution of chilled fresh and minimally processed food
      products are developed. The SLDS integrates predictive kinetic models of food
      spoilage, data on initial quality from rapid techniques, and the capacity to
      continuously monitor temperature history of the food product with Time
      Temperature Integrators (TTIs) into an effective chill chain management tool that
      leads to an improved narrow distribution of quality at consumption time,
      effectively reducing the probability of products consumed past shelf life end.
      The applicability and effectiveness of the SLDS is demonstrated and evaluated
      based on actual food spoilage and TTI kinetics and chill chain data employing the
      Monte Carlo simulation method.

PMID- 11456192
TI  - Total mercury levels in muscle tissue of swordfish (Xiphias gladius) and bluefin
      tuna (Thunnus thynnus) from the Mediterranean Sea (Italy).
AB  - This study was carried out to determine the current levels of total mercury in
      the muscle tissue of swordfish (Xiphias gladius) and bluefin tuna (Thunnus
      thynnus) caught in the Mediterranean Sea with the purpose of ascertaining whether
      the concentrations exceeded the maximum level fixed by the European Commission
      Decision. In addition, specimens of each species were divided into different
      ranges of weight to investigate the influence of size on mercury accumulation in
      order to provide data upon which commercial fishing strategies and marketing of
      swordfish and bluefin tuna may be based. Higher mean levels of total mercury were
      found in bluefin tuna (1.02 microg g(-1) wet wt) than in swordfish (0.49 microg
      g(-1) wet wt). In 4.3% of swordfish and in 44.3% of bluefin tuna analyzed, total
      mercury concentrations exceeded the maximum level fixed by the European
      Commission Decision (Hg = 1 microg g(-1) wet wt). Besides, for bluefin tuna the
      total mercury level variability observed, due to size, suggests that there should
      be greater regulatory control by the authorities.

PMID- 11456193
TI  - Fatty acid modifications and cholesterol oxidation in pork loin during frying at
      different temperatures.
AB  - The effect of frying with sunflower oil for 4 min at different temperatures (160,
      170, and 180 degrees C) on fatty acids and cholesterol of pork loin meat was
      studied. Total fat content increased from 5.6% in fresh loin to 7.3, 7.8, and
      12.1% at 160, 170, and 180 degrees C, respectively. Interactions with culinary
      fat gave rise to a significant increase in unsaturated acids/saturated acids and
      polyunsaturated acids/saturated acids ratios, which could be considered an
      advantage from a nutritional point of view. Less than 1 ppm (microg/g of sample)
      of cholesterol oxidation products was detected in fresh loin, whereas fried loin
      pork contained between 8.58 and 10.89 ppm. 7-Ketocholesterol (5.99 to 8.47 ppm in
      fried samples) and 7beta-hydroxycholesterol (1.43 to 2.55 ppm in fried samples)
      were the main cholesterol oxidation products. Cholestanetriol was not detected in
      any sample, and small quantities of 25-hydroxycholesterol and 5,6alpha
      epoxycholesterol were found in the fried sample.

PMID- 11456194
TI  - Evaluation of thin agar layer method for recovery of acid-injured foodborne
      pathogens.
AB  - The thin agar layer (TAL) method of Kang and Fung was used to enumerate acid
      injured foodborne pathogens. This method involves overlaying 14 ml of
      nonselective medium (tryptic soy agar [TSA]) onto a prepoured and solidified
      pathogen-specific, selective medium in a petri dish. After surface plating,
      injured cells resuscitated and grew on TSA during the first few hours of
      incubation; then, the selective agents from the selective medium diffused to the
      top layer, interacted with the recovered microorganisms, and started to produce
      typical reactions. Foodborne pathogens were exposed to 2% acetic acid for 1, 2,
      or 4 min, and the recovery rate with the TAL method was compared with the rate of
      TSA and pathogen-specific, selective media. No significant difference occurred
      between TSA and TAL (P > 0.05) for enumeration of acid-injured Escherichia coli
      O157:H7, Salmonella Typhimurium, Staphylococcus aureus, and Yersinia
      enterocolitica, and both recovered significantly higher numbers than the
      selective medium for each respective pathogen (P < 0.05). For recovery of acid
      injured Listeria monocytogenes, no difference (P > 0.05) occurred among TSA, TAL,
      and selective media. However, fewer cells were recovered in the selective media.
      The TAL method is a one-step, convenient procedure for recovery of acid-injured
      cells.

PMID- 11456195
TI  - Determination of fumonisin B1 and B2 in corn and corn-based products in Turkey by
      high-performance liquid chromatography.
AB  - The purpose of this study was to investigate fumonisin B1 (FB1)- and B2 (FB2)
      contaminated corn and corn-based products consumed especially by the Turkish
      population. FB1 and FB2 were detected using high-performance liquid
      chromatography with fluorescence detection. The total number of commercially
      available corn and corn-based product samples analyzed in this research was 82.
      The recoveries were found to be 94.4 +/- 4.62% and 86.5 +/- 4.86% for cornmeal
      spiked with known amounts of FB1 and FB2 (1 ppm), respectively. The minimum
      detectable amount for the o-phthaldialdehyde derivatives of FB1 and FB2 were 1 ng
      and 5 ng, respectively. Detected levels of FB1 were between 0.25 ppm and 2.66 ppm
      in 25.6% of the samples, and detected level of FB2 in a single cornmeal sample
      was 0.55 ppm.

PMID- 11456196
TI  - Occurrence of Burkholderia cepacia in foods and waters: clinical implications for
      patients with cystic fibrosis.
AB  - Two hundred forty-eight retail "ready-to-eat" foodstuffs in eight food categories
      and 134 waters categorized into nine types were analyzed for the presence of the
      Burkholderia cepacia complex of organisms. Of these, 14 of 26 (53.8%) samples of
      raw unpasteurized bovine milk were positive for this organism. Consumption of raw
      unpasteurized milk may therefore act as a potential source of infection with this
      organism, which is of particular concern for patients with cystic fibrosis, where
      colonization and infection with this organism can lead to a fatal necrotizing
      pneumonia and premature death. In addition to the associated risk of infection
      from fecal pathogens, patients with cystic fibrosis should therefore avoid the
      consumption of raw unpasteurized milk to minimize the risk of becoming infected
      with this organism.

PMID- 11456197
TI  - Standardization of a method to determine the efficacy of sanitizers in
      inactivating human pathogenic microorganisms on raw fruits and vegetables.
AB  - The efficacy of sanitizers in killing human pathogenic microorganisms on a wide
      range of whole and fresh-cut fruits and vegetables has been studied extensively.
      Numerous challenge studies to determine the effects of storage conditions on
      survival and growth of pathogens on raw produce have also been reported. Results
      of these studies are often difficult to assess because of the lack of sufficient
      reporting of methods or, comparatively, because of variations in procedures for
      preparing and applying inocula to produce, conditions for treatment and storage,
      and procedures for enumerating pathogens. There is a need for a standard method
      to accurately determine the presence and populations of pathogenic microorganisms
      on produce. The adoption of standard, well-characterized reference strains would
      benefit a comparative assessment of a basic method among laboratories. A single
      protocol will not be suitable for all fruits and vegetables. Modifications of a
      basic method will be necessary to achieve maximum recovery of pathogens on
      various types of produce subjected to different sanitizer or storage treatments.
      This article discusses parameters that must be considered in the course of
      developing a basic standard method against which these modifications could be
      made.

PMID- 11456198
TI  - Effect of phage on survival of Salmonella enteritidis during manufacture and
      storage of cheddar cheese made from raw and pasteurized milk.
AB  - The ability of Salmonella Enteritidis to survive in the presence of phage, SJ2,
      during manufacture, ripening, and storage of Cheddar cheese produced from raw and
      pasteurized milk was investigated. Raw milk and pasteurized milk were inoculated
      to contain 10(4) CFU/ml of a luminescent strain of Salmonella Enteritidis (lux)
      and 10(8) PFU/ml SJ2 phage. The milks were processed into Cheddar cheese
      following standard procedures. Cheese samples were examined for Salmonella
      Enteritidis (lux), lactic acid bacteria, molds and yeasts, coliforms, and total
      counts, while moisture, fat, salt, and pH values were also measured. Salmonella
      Enteritidis (lux) was enumerated in duplicate samples by surface plating on
      MacConkey novobiocin agar. Bioluminescent colonies of Salmonella Enteritidis were
      identified in the NightOwl molecular imager. Samples were taken over a period of
      99 days. Counts of Salmonella Enteritidis (lux) decreased by 1 to 2 log cycles in
      raw and pasteurized milk cheeses made from milk containing phage. In cheeses made
      from milks to which phage was not added, there was an increase in Salmonella
      counts of about 1 log cycle. Lower counts of Salmonella Enteritidis (lux) were
      observed after 24 h in pasteurized milk cheese containing phage compared to
      Salmonella counts in raw milk cheese with phage. Salmonella Enteritidis (lux)
      survived in raw milk and pasteurized milk cheese without phage, reaching a final
      concentration of 10(3) CFU/g after 99 days of storage at 8 degrees C. Salmonella
      did not survive in pasteurized milk cheese after 89 days in the presence of
      phage. However, Salmonella counts of approximately 50 CFU/g were observed in raw
      milk cheese containing phage even after 99 days of storage. In conclusion, this
      study demonstrates that the addition of phage may be a useful adjunct to reduce
      the ability of Salmonella to survive in Cheddar cheese made from both raw and
      pasteurized milk.

PMID- 11456199
TI  - Thermal inactivation kinetics of Salmonella spp. within intact eggs heated using
      humidity-controlled air.
AB  - The heat resistance of six strains of Salmonella (including Enteritidis,
      Heidelberg, and Typhimurium) in liquid whole egg and shell eggs was determined.
      Decimal reduction times (D-values) of each of the six strains were determined in
      liquid whole egg heated at 56.7 degrees C within glass capillary tubes immersed
      in a water bath. D-values ranged from 3.05 to 4.09 min, and significant
      differences were observed between the strains tested (alpha = 0.05). In addition,
      approximately 7 log10 CFU/g of a six-strain cocktail was inoculated into the
      geometric center of raw shell eggs and the eggs heated at 57.2 degrees C using
      convection currents of humidity-controlled air. D-values of the pooled
      salmonellae ranged from 5.49 to 6.12 min within the center of intact shell eggs.
      A heating period of 70 min or more resulted in no surviving salmonellae being
      detected (i.e., an 8.7-log reduction per egg).

PMID- 11456200
TI  - The effect of lairage on Salmonella isolation from market swine.
AB  - The objective of this paper was to evaluate the effect of lairage (holding >12 h
      during transport to slaughter) in clean facilities on Salmonella isolation from
      market swine. We tested 30 market-bound pigs (about 240 lb [110 kg]) on each of
      10 occasions from an Iowa farrow-to-finish operation with about 600 sows. All
      pigs were slaughtered, and samples were collected at a large Midwest abattoir. On
      the farm, fecal samples were collected for culture of Salmonella. Pigs were
      alternately assigned to a lairage treatment (holding in a clean, disinfected
      facility at the National Animal Disease Center) group or a control group
      (remaining on the farm). After about 18 h, both groups were transported (about
      137 km) to a large Midwest abattoir, commingled, and slaughtered. After
      slaughter, samples were collected for culture of Salmonella (feces from the
      distal colon, ileocecal lymph nodes, cecal contents, ventral thoracic lymph
      nodes, subiliac lymph nodes, and carcass swabs). Diaphragm sections were
      collected for serum ELISA. Salmonella enterica Derby was the only serotype
      isolated from farm fecal samples (3.4%, 10 of 290). Multiple serotypes (n = 17)
      were isolated from 71.8% (196 of 273) of the pigs when abattoir-collected samples
      were cultured: cecal contents (21.2%. 58 of 273), distal colon contents (52%, 142
      of 273), and ileocecal lymph nodes (43.6%, 119 of 273). There were lower
      Salmonella isolation rates from the lairaged pigs (P < 0.05). The predominant
      serotype isolated at the abattoir varied by week of the study. This study
      suggests that pigs became internally contaminated with Salmonella after leaving
      the farm, possibly while in the abattoir holding pens, and that 18 h lairage, in
      clean facilities, does not increase shedding.

PMID- 11456201
TI  - Survival and infectivity of Salmonella choleraesuis in swine feces.
AB  - Many serotypes of Salmonella survive well in the environment. Conversely, it is
      believed that Salmonella Choleraesuis, the host-adapted serotype of swine, does
      not survive well outside the host. We examined the survival capability of
      Salmonella Choleraesuis in swine feces. Six pigs were infected with Salmonella
      Choleraesuis and feces were collected and pooled on days 2, 4, 7, and 10
      postinoculation (PI). Feces were stored in a wet and a dry form, and survival was
      measured over 13 months. Salmonella Choleraesuis was recovered from wet feces
      through 3 months of storage. In a desiccated (dry) form, Salmonella Choleraesuis
      was recovered from at least 13 months. Salmonella Choleraesuis shed from swine
      prior to 4 days PI did not survive as well as that shed 4 days PI or later. We
      also examined the infectivity of Salmonella Choleraesuis resident in dry feces.
      Six- or 13-week-old pigs were inoculated with dry feces that had been stored
      either 2 months or 4 months, respectively. Pigs were inoculated either
      intranasally or by mixing dry feces with the swine ration. Although clinical
      signs were mild, Salmonella Choleraesuis was widely disseminated among the
      tissues of all the pigs inoculated. This study demonstrates that Salmonella
      Choleraesuis remains viable and infective in the environment. Therefore,
      contaminated fecal matter can serve as a reservoir for Salmonella Choleraesuis as
      well as other Salmonella spp. Control measures must consider this environmental
      reservoir as a source of new infections.

PMID- 11456202
TI  - Fate of Escherichia coli O157:H7, Salmonella typhimurium DT 104, and Listeria
      monocytogenes in fresh meat decontamination fluids at 4 and 10 degrees C.
AB  - Bacterial pathogens may colonize meat plants and increase food safety risks
      following survival, stress hardening, or proliferation in meat decontamination
      fluids (washings). The objective of this study was to evaluate the ability of
      Escherichia coli O157:H7, Salmonella Typhimurium DT 104, and Listeria
      monocytogenes to survive or grow in spray-washing fluids from fresh beef top
      rounds sprayed with water (10 or 85 degrees C) or acid solutions (2% lactic or
      acetic acid, 55 degrees C) during storage of the washings at 4 or 10 degrees C in
      air to simulate plant conditions. Inoculated Salmonella Typhimurium DT 104 (5.4
      +/- 0.1 log CFU/ml) died off in lactate (pH 2.4 +/- 0.1) and acetate (pH 3.1 +/-
      0.2) washings by 2 days at either storage temperature. In contrast, inoculated E.
      coli O157:H7 (5.2 +/- 0.1 log CFU/ml) and L. monocytogenes (5.4 +/- 0.1 log
      CFU/ml) survived in lactate washings for at least 2 days and in acetate washings
      for at least 7 and 4 days, respectively; their survival was better in acidic
      washings stored at 4 degrees C than at 10 degrees C. All inoculated pathogens
      survived in nonacid (pH > 6.0) washings, but their fate was different. E. coli
      O157:H7 did not grow at either temperature in water washings, whereas Salmonella
      Typhimurium DT 104 failed to multiply at 4 degrees C but increased by
      approximately 2 logs at 10 degrees C. L. monocytogenes multiplied (0.6 to 1.3
      logs) at both temperatures in water washings. These results indicated that
      bacterial pathogens may survive for several days in acidic, and proliferate in
      water, washings of meat, serving as potential cross-contamination sources, if
      pathogen niches are established in the plant. The responses of surviving
      pathogens in meat decontamination waste fluids to acid or other stresses need to
      be addressed to better evaluate potential food safety risks.

PMID- 11456203
TI  - Survival of Escherichia coli O157:H7, Salmonella typhimurium and Listeria
      monocytogenes in and on vacuum packaged Lebanon bologna stored at 3.6 and 13.0
      degrees C.
AB  - Escherichia coli O157:H7, Salmonella Typhimurium, or Listeria monocytogenes was
      spread onto the surface of Lebanon bologna luncheon slices using sterile glass
      rods. The inoculated slices were stacked and vacuum packaged. The packages were
      stored at 3.6 or 13 degrees C. The foodborne pathogens. E. coli O157:H7,
      Salmonella Typhimurium, or L. monocytogenes were reduced in Lebanon bologna
      during storage at 3.6 or 13 degrees C. The higher storage temperature (13.0
      degrees C) resulted in significantly faster destruction of E. coli O157:H7 and L.
      monocytogenes, compared to storage at refrigeration temperature (3.6 degrees C)
      (P < 0.005). E. coli O157:H7 was the most resistant to destruction among the
      three foodborne pathogens. A linear destruction of E. coli O157:H7 occurred only
      after an initial lag period. Storage temperature did not have a significant
      effect on the rate of destruction of Salmonella Typhimurium. Foodborne pathogens
      inoculated prior to fermentation did not show any enhanced survival compared to
      control cells (inoculated after fermentation) during storage of the Lebanon
      bologna at 3.6 degrees C.

PMID- 11456204
TI  - Reduction in levels of Escherichia coli O157:H7 in apple cider by pulsed electric
      fields.
AB  - Many studies have demonstrated that high voltage pulsed electric field (PEF)
      treatment has lethal effects on microorganisms including Escherichia coli
      O157:H7; however, the survival of this pathogen through the PEF treatment is not
      fully understood. Fresh apple cider samples inoculated with E. coli O157:H7
      strain EC920026 were treated with 10, 20, and 30 instant charge reversal pulses
      at electric field strengths of 60, 70, and 80 kV/cm, at 20, 30, and 42 degrees C.
      To accurately evaluate the lethality of apple cider processing steps, counts were
      determined on tryptic soy agar (TSA) and sorbitol MacConkey agar (SMA) to
      estimate the number of injured and uninjured E. coli O157:H7 cells after PEF
      treatment. Cell death increased significantly with increased temperatures and
      electric field strengths. A maximum of 5.35-log10 CFU/ml (P < 0.05) reduction in
      cell population was achieved in samples treated with 30 pulses and 80 kV/cm at 42
      degrees C. Cell injury measured by the difference between TSA and SMA counts was
      found to be insignificant (P > 0.05). Under extreme conditions, a 5.91-log10
      CFU/ml reduction in cell population was accomplished when treating samples with
      10 pulses and 90 kV/cm at 42 degrees C. PEF treatment, when combined with the
      addition of cinnamon or nisin, triggered cell death, resulting in a reduction in
      E. coli O157:H7 count of 6 to 8 log10 CFU/ml. Overall, the combination of PEF and
      heat treatment was demonstrated to be an effective pasteurization technique by
      sufficiently reducing the number of viable E. coli O157:H7 cells in fresh apple
      cider to meet U.S. Federal Drug Administration recommendations.

PMID- 11456205
TI  - Acid stress, starvation, and cold stress affect poststress behavior of
      Escherichia coli O157:H7 and nonpathogenic Escherichia coli.
AB  - The effects of acid shock, acid adaptation, starvation, and cold stress of
      Escherichia coli O157:H7 (ATCC 43895), an rpoS mutant (FRIK 816-3), and
      nonpathogenic E. coli (ATCC 25922) on poststress heat resistance and freeze-thaw
      resistance were investigated. Following stress, heat tolerance at 56 degrees C
      and freeze-thaw resistance at -20 to 21 degrees C were determined. Heat and
      freeze-thaw resistance of E. coli O157:H7 and nonpathogenic E. coli was enhanced
      after acid adaptation and starvation. Following cold stress, heat resistance of
      E. coli O157:H7 and nonpathogenic E. coli was decreased, while freeze-thaw
      resistance was increased. Heat and freeze-thaw resistance of the rpoS mutant was
      enhanced only after acid adaptation. Increased or decreased tolerance of acid
      adapted, starved, or cold-stressed E. coli O157:H7 cells to heat or freeze-thaw
      processes should be considered when processing minimally processed or extended
      shelf-life foods.

PMID- 11456206
TI  - Sensitivity of acid-adapted and acid-shocked Shigella flexneri to reduced pH
      achieved with acetic, lactic, and propionic acids.
AB  - Survival and growth characteristics of unadapted, acid-adapted, and acid-shocked
      Shigella flexneri 2a cells in acidified (pH 3.5 to 5.5) tryptic soy broth with
      0.25% glucose (TSB) and tryptic soy agar (TSA) were determined. S. flexneri was
      grown at 37 degrees C for 18 h in tryptic soy broth without glucose (TSBNG)
      (unadapted) and TSBNG supplemented with 1% glucose (TSBG) (acid-adapted). Cells
      grown in TSBNG were acid shocked by adjusting 16-h cultures to pH 5.05 +/- 0.05
      with lactic acid. Cells were then inoculated into TSB acidified with acetic,
      lactic, or propionic acids to pH 5.5, 4.5, or 3.5 and incubated at 37 degrees C
      for 6 h. The order of lethality at a given pH was lactic acid < acetic acid <
      propionic acid. Significantly (P < or = 0.05) higher numbers of acid-adapted
      cells, compared to acid-shocked and unadapted cells, were recovered from TSB
      acidified (pH 3.5) with lactic or acetic acids. None of the cells survived a 30
      min exposure in TSB acidified with propionic acid to pH 3.5. When the three cell
      types were plated on TSA acidified with lactic, acetic, or propionic acids at pH
      < or = 4.5, < or = 5.5, and < or = 5.5, respectively, visible colonies were not
      detected. Viable unadapted, acid-adapted, and acid-shocked cells were, however,
      recovered from TSA acidified with all three acids at pH > or = 4.5. Acid-adapted
      and, to a lesser extent, acid-shocked cells survived at lower pH than did
      unadapted cells, indicating that prior exposure to mild acidic environment
      results in increased acid resistance. Survival of S. flexneri at a given pH was
      influenced by the type of acidulant used, a response characteristic exhibited by
      other gram-negative enteric pathogens.

PMID- 11456207
TI  - Comparison of methods for recovery and enumeration of Campylobacter from freshly
      processed broilers.
AB  - Most traditional Campylobacter detection and enumeration procedures are difficult
      and time consuming. Estimations of Campylobacter populations by the most probable
      number (MPN) method are especially laborious. The objective of this collaborative
      study, performed in duplicate in Agricultural Research Service and Food Safety
      Inspection Service laboratories, was to compare two MPN procedures (utilizing
      different selective enrichment broths and plating media) to the direct plating
      technique for enumeration of Campylobacter from freshly processed (postchill,
      postdrip) broiler chicken carcasses. Results obtained from the direct plating of
      carcass rinse samples on Campy-cefex agar were not significantly different (P >
      0.05) from an MPN procedure employing Hunt's Campylobacter selective enrichment
      broth followed by recovery on modified Campylobacter charcoal differential agar.
      However, both of these procedures provided significantly (P < 0.05) better
      recovery than a second MPN procedure using Rosef's selective enrichment broth
      followed by plating on Mueller-Hinton blood agar with antibiotics. The direct
      plating method offers a more simple, less expensive, more rapid alternative to
      traditional MPN procedures for estimating Campylobacter populations associated
      with freshly processed broiler carcasses.

PMID- 11456208
TI  - Development and validation of growth model for Yersinia enterocolitica in cooked
      chicken meats packaged under various atmosphere packaging and stored at different
      temperatures.
AB  - Mathematical models that can predict the growth of Yersinia enterocolitica in
      chicken meats were evaluated in this study. The growth curves for Y.
      enterocolitica in chicken meats variously packaged (air, vacuum, and modified
      atmosphere packaging [MAP]) and stored at various temperatures (4, 10, 16, 22,
      28, and 34 degrees C) were constructed. The Gompertz model was applied to fit
      each of the experimental curves for the conditions mentioned above. The
      variations in the parameters, including lag time (lambda) and specific growth
      rate (mu), at various temperatures were then described by the following models:
      the variations in lag time were described by the Adair and Smith models and the
      variations in the specific growth rate were described by the Ratkowsky and
      Zwietering models. The various models were then compared using graphical and
      mathematical analyses such as mean square error (MSE), regression coefficient
      (r2), bias factor, and accuracy factor. The results indicate that the mean r
      values in the Gompertz model for chicken meats packaged in air, vacuum, and MAP
      were 0.99, 0.99, and 0.95, respectively. The lag time modeled with the Adair and
      Smith functions exhibited a greater variance and demonstrated larger errors. The
      MSEs were 0.0015 and 0.0017 for Ratkowsky and Zwietering models, respectively.
      The r2 values in the Ratkowsky and Zwietering models were both 0.99. The bias
      factor was 1.017 for the Ratkowsky model and 1.096 for the Zwietering model. The
      accuracy factor of the Zwietering model was 1.174, which was lower than that in
      the Ratkowsky model (1.275), indicating that the former model was more accurate
      than the latter in predicting the specific growth rate of Y. enterocolitica in
      chicken meats.

PMID- 11456209
TI  - Prevalence of Listeria monocytogenes in broilers at the abattoir, processing
      plant, and retail level.
AB  - The environment and products from two broiler abattoirs and processing plants and
      raw broiler pieces at the retail level were sampled for Listeria monocytogenes in
      order to evaluate the contamination level of the broiler carcasses and products.
      Sampling started in the slaughtering process and finished with raw broiler meat
      or ready-to-eat cooked product. Sampling sites positive for L. monocytogenes at
      the broiler abattoir were the air chiller, the skin-removing machine, and the
      conveyor belt leading to the packaging area. The L monocytogenes contamination
      rate varied from 1 to 19% between the two plants studied. Furthermore, 62% (38 of
      61) of the raw broiler pieces, bought from retail stores, were positive for L.
      monocytogenes. Altogether, 136 L. monocytogenes isolates were obtained for
      serotyping and pulsed-field gel electrophoresis (PFGE) characterization performed
      with two rare-cutting enzymes (ApaI and AscI). Altogether three serotypes (1/2a,
      1/2c, and 4b) and 14 different PFGE types were obtained using information
      provided from both ApaI and AscI patterns for discrimination basis. The two
      broiler abattoirs studied did not share the same PFGE types. However, the same
      PFGE types found in the raw broiler pieces at the retail level were also found in
      the broiler abattoirs where the broilers had been slaughtered.

PMID- 11456210
TI  - Developing guidance for budget impact analysis.
AB  - The role of economic evaluation in the efficient allocation of healthcare
      resources has been widely debated. Whilst economic evidence is undoubtedly useful
      to purchasers, it does not address the issue of affordability which is an
      increasing concern. Healthcare purchasers are concerned not just with maximising
      efficiency but also with the more simplistic goal of remaining within their
      annual budgets. These two objectives are not necessarily consistent. This paper
      examines the issue of affordability, the relationship between affordability and
      efficiency and builds the case for why there is a growing need for budget impact
      models to complement economic evaluation. Guidance currently available for such
      models is also examined and it is concluded that this guidance is currently
      insufficient. Some of these insufficiencies are addressed and some thoughts on
      what constitutes best practice in budget impact modelling are suggested. These
      suggestions include consideration of transparency, clarity of perspective,
      reliability of data sources, the relationship between intermediate and final end
      points and rates of adoption of new therapies. They also include the impact of
      intervention by population subgroups or indications, reporting of results,
      probability of re-deploying resources, the time horizon, exploring uncertainty
      and sensitivity analysis, and decision-maker access to the model. Due to the
      nature of budget impact models, the paper does not deliver stringent
      methodological guidance on modelling. The intention was to provide some
      suggestions of best practice in addition to some foundations upon which future
      research can build.

PMID- 11456211
TI  - An economic overview of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and
      morbidity. Relatively few pharmacoeconomic studies have been conducted on this
      disease. This article reviews available information about the utilisation of
      healthcare resources and cost of care, and the cost or cost effectiveness of
      therapeutic interventions reported for this disease. Burden-of-illness data
      indicate that hospital care, medications and oxygen therapy were the major cost
      drivers in these studies. Mean annual Medicare expenditures in the US were
      $US11,841 (2000 values) for patients with COPD compared with $US4,901 for all
      covered patients. Utilisation was skewed; the most expensive 10% of the Medicare
      beneficiaries accounted for nearly 50% of total expenditures for this disease.
      Costs are associated with health status, age, physician specialty, geographic
      location and type of insurance coverage. Six types of interventions were assessed
      in the literature--pharmacotherapy, oxygen therapy, home care, surgery, exercise
      and rehabilitation and health education. The studies used different analytic
      strategies (e.g. cost-minimisation and cost-effectiveness analyses) and even
      within the realm of cost-effectiveness analyses, no uniformity existed as to how
      outcome was measured. Patient severity was not always delineated, and the length
      of the follow-up period, while quite short, varied. Only 11 of the 34 evaluations
      were based on randomised controlled trials. Cost-minimisation studies generally
      found no significant difference in the cost of antimicrobial treatment for first
      line, second-line and third-line agents. Studies of bronchodilators indicated
      that ipratropium bromide alone or in combination with salbutamol (albuterol) was
      the preferred medication. The major area for achieving cost savings is by
      reducing hospital utilisation. As the annual rate of hospitalisation is
      relatively low, large patient samples will be required to demonstrate an economic
      advantage for a new therapy. The major challenges will be financing such a study,
      and selecting an outcome measure that satisfies both clinical and economic
      conventions.

PMID- 11456212
TI  - Quality of life in irritable bowel syndrome.
AB  - Quality-of-life (QOL) assessment is becoming increasingly important in the
      evaluation of the impact of disease and the effect of therapy. This is
      particularly so forirritable bowel syndrome (IBS) where there is often a tendency
      for a chronic clinical course, but with no associated mortality. Instruments used
      to study quality of life may be generic or disease specific, and care needs to be
      taken to ensure that the instrument used has been adequately validated for the
      purpose intended. Several disease-specific instruments [Irritable Bowel Syndrome
      Quality of Life (IBS-QOL, IBSQOL) and Functional Digestive Disorders Quality of
      Life (FDDQL)], in addition to generic measures, are now available for use in IBS.
      Quality of life in patients with IBS is surprisingly poor, particularly in the
      population seeking healthcare, where it can be compared with conditions which
      carry a high mortality, such as ischaemic heart disease, heart failure and
      diabetes mellitus. Pain severity appears to be an important factor in determining
      quality of life in IBS, although bowel disturbance and psychological difficulties
      are also likely to be important. There is limited data on the effect of treatment
      of IBS on quality of life. Improvement has been reported with dietry
      modification, drug treatments and hypnotherapy. It is likely that, in the future,
      QOL measures will become increasingly used as secondary end-points in therapeutic
      trials in IBS.

PMID- 11456213
TI  - An epidemiological approach to assess the economic burden of NSAID-induced
      gastrointestinal events in The Netherlands.
AB  - OBJECTIVE: To use the population attributable risk (PAR) to estimate the
      treatment costs resulting from nonsteroidal anti-inflammatory drug (NSAID)
      induced gastrointestinal (GI) morbidity. DESIGN: Two case-control studies with
      the following outcomes: (i) the start of therapy with gastroprotective agents
      (GPAs) and (ii) hospitalisations for GI events. SETTING: Community-dwelling
      inhabitants of defined areas in The Netherlands covering the period 1989 to 1998.
      All analyses were performed from the perspective of a third-party payer. METHODS:
      Risk and exposure data were obtained from the Dutch PHARMO system, a population
      based register of drug-dispensing records and hospital records. The PAR was
      estimated based on stratum-specific prevalence estimates of NSAID use and the
      corresponding odds ratios (ORs) obtained from the case-control studies. Cost data
      were obtained from Dutch national hospital discharge records and tariffs. Annual
      treatment costs of NSAID-induced GI events were calculated based on the PAR in
      the sample population and extrapolated to the total population using national
      demographic data. RESULTS: The adjusted ORs for starting GPA use and
      hospitalisation for GI events were 6.6 [95% confidence interval (CI): 5.5 to 7.8]
      and 5.0 (95% CI: 4.0 to 6.2), respectively, in NSAID users compared with
      controls. Variation of OR with age among NSAID users suggested that prevention of
      GI events is most efficient among the elderly. The total annual cost (1998
      values) of GPA use and hospitalisations for GI events attributable to the use of
      NSAIDs was 59 million euro (EUR) [95% CI: EUR38.5 million to EUR98 million]. More
      than 65% of these NSAID-induced costs, EUR38 million, can be attributed to long
      term users of NSAIDs, representing only 9.3% of all users of NSAIDs. CONCLUSIONS:
      The PAR can be used to estimate the costs of drug-induced morbidity and changes
      in costs resulting from substitutions with other drugs. For each EUR1.00 spent on
      NSAIDs, an additional EUR0.68 (excluding costs for prophylactic treatment) can be
      added for the treatment of GI adverse events.

PMID- 11456214
TI  - International validation of the CLAU-S quality-of-life questionnaire for use in
      patients with intermittent claudication.
AB  - BACKGROUND: Intermittent claudication (IC) occurs in patients with peripheral
      occlusive arterial disease and results in leg pain after walking a certain
      distance - the claudication distance. Until recently, no specific questionnaire
      has been available to measure quality of life in patients with IC. OBJECTIVES: To
      validate the Claudication Scale (CLAU-S) questionnaire in patients in France, the
      UK, Germany and Belgium. METHODS: Patients completed the CLAU-S questionnaire and
      provided demographic and clinical data. Pooled data were examined for
      psychometric and structural validity and test-retest reliability. Structural
      equation modelling (SEM) was used to confirm that the questionnaire was measuring
      the causal relationships involved in IC in each of the language groups studied.
      RESULTS: Cross-sectional and factor analysis confirmed the validity of the
      questionnaire in the pooled patient population. Item convergent and discriminant
      coefficients and internal consistency reliability coefficients met or exceeded
      standard criteria. Principal component analysis confirmed the factorial
      structure. The underlying causal relationships in IC were identified using SEM
      and were consistent in all language groups studied. CONCLUSIONS: The CLAU-S
      questionnaire has undergone validation in English, French, German and Flemish and
      has a very satisfactory validity in these languages.

PMID- 11456215
TI  - Torasemide: a pharmacoeconomic review of its use in chronic heart failure.
AB  - Torasemide is a loop diuretic used for the treatment of hypertension and for
      oedema in chronic heart failure (CHF), renal failure and cirrhosis. The efficacy
      of torasemide in reducing salt and water retention in CHF has been established in
      double-blind comparative studies against furosemide. Torasemide has been shown to
      be at least as effective as furosemide in terms of total volume of urine excreted
      and also has a longer duration of action. The efficacy of torasemide (in terms of
      improved CHF symptoms and reduced pulmonary congestion, oedema and bodyweight)
      has been shown in randomised controlled trials and confirmed in large
      postmarketing studies. In addition, data from postmarketing studies have shown
      that patients receiving torasemide had significantly reduced hospital admission
      rates compared with patients receiving furosemide. Pharmacoeconomic assessments
      of torasemide have focused on its effect in reducing hospitalisation.
      Hospitalisation costs due to CHF decreased by 86% during the 11.2-month period of
      torasemide treatment, compared with the 6-month period prior to treatment, in a
      US retrospective study assessing medical and pharmacy claims data. Overall,
      average monthly costs for patients decreased by 56.6% after 5.1 months (from
      $US1,897.28 to $US823.70 per patient per month; PPPM), and by 76% after 11.2
      months (from $US1,944.76 to $US470.76 PPPM) of torasemide treatment. In the
      furosemide group, average monthly costs for patients increased moderately from
      $US227.28 to $US261.18 PPPM after 12 months. Direct comparison of the torasemide
      and furosemide study groups was not possible because the group receiving
      torasemide had much higher healthcare resource use at baseline. Compared with
      furosemide, torasemide was associated with reduced rates of hospital admissions
      for CHF and/or cardiovascular causes in 3 studies, a retrospective analysis
      conducted in Germany, a prospective US study of patients enrolled from hospital
      admissions and a decision-analysis model. As a result, the direct costs of
      treatment for CHF or cardiovascular diseases for patients treated with torasemide
      were less than those with furosemide. However, in the US study, there was no
      statistically significant difference in hospital admissions for all causes and/or
      in overall direct medical costs, although the study was not powered to show this.
      In another US study of managed care patients with New York Heart Association
      (NYHA) class II or III CHF, no difference in clinical or economic outcomes was
      observed between patients taking torasemide or furosemide; despite the higher
      acquisition costs for torasemide, total costs were similar for both groups.
      Torasemide was found to be more cost effective than furosemide in terms of cost
      per patient with improved functional (NYHA) class of CHF severity in a
      retrospective German analysis, although this measure is not ideal. This study
      also evaluated indirect costs (for loss of productivity of employed patients) and
      resultssuggest torasemide has a favourable effect in reducing days off work
      compared with furosemide, although the population of employed patients in the
      study was very small. Torasemide has been shown to improve some measures of
      quality of life in 2 studies. It was associated with higher quality-of-life
      scores than furosemide in a 6-month study, but the differences were only
      significant at month 4. In another study, torasemide significantly improved
      fatigue, but full study details are yet to be published. CONCLUSIONS: Despite the
      higher acquisition cost of torasemide over furosemide, pharmacoeconomic analyses
      have shown that torasemide is likely to reduce overall treatment costs of CHF by
      reducing hospital admissions and readmissions. Torasemide has generally shown
      clinical and economic advantages over furosemide, although more long term data
      are needed to confirm these results and to further investigate effects on quality
      of life. There are limitations to the currently available pharmacoeconomic data,
      but present data support the use of torasemide as a first-line option for
      diuretic therapy in patients with CHF presenting with oedema and especially in
      those patients not achieving relief of symptoms with furosemide.

PMID- 11456216
TI  - Cyclosporin A induces the opening of a potassium-selective channel in higher
      plant mitochondria.
AB  - The immunosuppressive drug, cyclosporin A (CsA), induces the generation of a
      transmembrane electrical potential difference (deltapsi) in deenergized plant
      mitochondria incubated in sucrose-based media. Build up of deltapsi is prevented
      by external monovalent cations in the order K+ > Rb+ = Li+ > Na+, or by the
      protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which also
      collapses the deltapsi generated by CsA. Entry of K+ into mitochondria can be
      monitored as swelling by incubating the organelles in a medium containing KCl to
      maintain constant osmolarity. This swelling is inhibited by ATP and stimulated by
      CsA or valinomycin. In addition, in mitochondria energized by succinate, KCl
      causes a dissipation of deltapsi, with sigmoidal kinetics, which is favored by
      CsA. Therefore, plant mitochondria appear to possess a K+ selective, voltage
      dependent channel, which is opened by CsA, regulated by the redox state, and
      inhibited by nucleotides. The hypothetical roles of this new K+ATP channel are
      discussed in relation to its potential involvement in mitochondrial volume
      regulation, thermogenesis, apoptosis, and/or prevention of reactive oxygen
      species formation in plants.

PMID- 11456217
TI  - Under conditions of insufficient permeability of VDAC1, external NADH may use the
      TOM complex channel to cross the outer membrane of Saccharomyces cerevisiae
      mitochondria.
AB  - Thus far, only three channel-forming activities have been identified in the outer
      membrane of the yeast Saccharomyces cerevisiae mitochondria. Two of them, namely
      the TOM complex channel (translocase of the outer membrane) and the PSC (peptide
      sensitive channel) participate in protein translocation and are probably
      identical, whereas a channel-forming protein called VDAC (voltage-dependent anion
      channel) serves as the major pathway for metabolites. The VDAC is present in two
      isoforms (VDAC1 and VDAC2) of which only VDAC1 has been shown to display channel
      forming activity. Moreover, the permeability of VDAC1 has been reported to be
      limited in uncoupled mitochondria of S. cerevisiae. The presented data indicate
      that in S. cerevisiae-uncoupled mitochondria, external NADH, applied at higher
      concentrations (above 50 nmoles per 0.1 mg of mitochondrial protein), may use the
      TOM complex channel, besides VDAC1, to cross the outer membrane. Thus, the
      permeability of VDAC1 could be a limiting step in transport of external NADH
      across the outer membrane and might be supplemented by the TOM complex channel.

PMID- 11456218
TI  - Dietary fat type and regular exercise affect mitochondrial composition and
      function depending on specific tissue in the rat.
AB  - Physical exercise and fatty acids have been studied in relation to mitochondrial
      composition and function in rat liver, heart, and skeletal muscle. Male rats were
      divided into two groups according to dietary fat type (virgin olive and sunflower
      oils). One-half of the animals from each group were subjected to a submaximal
      exercise for 8 weeks; the other half acted as sedentary controls. Coenzyme Q,
      cytochromes b, c + c1, a + a3 concentrations, and the activity of cytochrome c
      oxidase were determined. Regular exercise increased (P < 0.05) the concentration
      of the above-mentioned elements and the activity of the cytochrome c oxidase by
      roughly 50% in liver and skeletal muscle. In contrast, physical exercise
      decreased (P < 0.05) cytochrome c oxidase activity in the heart (in
      micromol/min/g, from 8.4+/-0.1 to 4.9+/-0.1 in virgin olive oil group and from
      9.7+/-0.1 to 6.7+/-0.2 in sunflower oil animals). Dietary fat type raised the
      levels of coenzyme Q, cytochromes, and cytochrome c oxidase activity in skeletal
      muscle (P < 0.05) among the rats fed sunflower oil. In conclusion, dietary fat
      type, regular exercise, and the specific tissue modulate composition and function
      of rat mitochondria.

PMID- 11456219
TI  - Bioenergetic responses of Synechocystis 6803 fatty acid desaturase mutants at low
      temperatures.
AB  - Fatty acid composition of the membrane lipids in the mesophilic cyanobacterium
      Synechocystis sp. PCC 6803 was altered in earlier work by targeted mutagenesis of
      genes for fatty acid desaturases. In this work, cells of several mutant strains,
      depleted in the unsaturated fatty acids in membrane lipids, were grown at 34
      degrees C. Spheroplasts (permeabilized cells) were prepared by lysozyme digestion
      of the cell wall followed by gentle osmotic shock. The bioenergetic parameters
      ATP formation, electron transport, and H+ uptake were measured at various
      temperatures. All three bioenergetic parameters for spheroplasts from wild-type
      cells (which had abundant polyunsaturated fatty acids) were active down to the
      lowest temperatures used (1 degrees - 2 degrees C). In two strains, which lacked
      the capacity to desaturate fatty acids at the A 12 position and at the A 12 and
      A6 positions (designated as desA- and desA-/desD-, respectively), the
      spheroplasts lost the capacity to form ATP (measured as phenazine methosulfate
      cyclic phosphorylation) at about 5 degrees C but retained electron transport
      (water oxidation-dependent ferricyanide reduction) and H+ uptake linked to
      phenazine methosulfate cyclic electron transport. It appears that the absence of
      the unsaturation of fatty acids in the A 12 and A6 positions blocks the ability
      of the photosynthetic membranes to couple a bioenergetically competent proton
      motive force to the ATP formation mechanism at temperatures below 5 degrees C. It
      remains to be determined whether the loss of ATP formation in the mutant strains
      is the failure of available protons to properly flow into the CF0CF1-ATP synthase
      or a failure in the CF1 part of the complex in coupling the dissipative H+ flow
      to the enzyme mechanism of the synthase.

PMID- 11456220
TI  - Neutral magnesium-dependent sphingomyelinase from liver plasma membrane:
      purification and inhibition by ubiquinol.
AB  - Plasma membranes isolated from pig liver contained almost no acid
      sphingomyelinase but significant neutral magnesium-dependent sphingomyelinase
      that was activated by phosphatidylserine. We report here the purification to
      apparent homogeneity of neutral sphingomyelinase of about 87 kDa from liver
      plasma membranes. The purified enzyme strictly required magnesium and had a
      neutral optimal pH. In contrast with neutral sphingomyelinase purified from other
      sources (such as brain), the enzyme purified from from liver plasma membrane was
      not inhibited by GSH and, strikingly, it was not activated by phosphatidylserine.
      Liver sphingomyelinase was inhibited by several lipophilic antioxidants in a dose
      dependent way. Ubiquinol-10 was more effective than alpha-tocopherol, alpha
      tocopherylquinone, alpha-tocopherylquinone, and ubiquinone-10, and inhibition was
      noncompetitive. Differential inhibition of neutral sphingomyelinase by
      antioxidants did not correlate with different levels of protection against lipid
      peroxidation. The purified sphingomyelinase was not inhibited significantly by
      ubiquinone-10 and ubiquinol- 10, but ubiquinol-0 and ubiquinone-0 inhibited by 30
      and 60% respectively. Our results demonstrate a direct inhibitory effect of
      ubiquinol on the plasma membrane n-SMase and support the participation of this
      molecule in the regulation of ceramide-mediated signaling.

PMID- 11456221
TI  - Purification and characterization of the membrane-bound complex of an ABC
      transporter, the histidine permease.
AB  - The bacterial histidine permease, an ABC transporter, from Salmonella typhimurium
      is composed of a membrane-bound complex, HisQMP2, comprising two hydrophobic
      subunits (HisQ and HisM), two copies of an ATP-hydrolyzing subunit, HisP, and a
      soluble receptor, HisJ. We describe the purification and characterization of
      HisQMP2 using a 6-histidines extension at the carboxy terminus of HisP
      [HisQMP2(his6)]. The purification is rapid and effective, giving a seven-fold
      purification with a yield of 85 and 98% purity. Two procedures are described
      differing in the detergent used (decanoylsucrose and octylglucoside,
      respectively) and in the presence of phospholipid. HisQMP2(his6) has ATPase and
      transport activities upon reconstitution into proteoliposomes (PLS).
      HisQMP2(his6) has a low level ATPase activity (intrinsic activity), which is
      stimulated to a different extent by the receptor--liganded and unliganded. Its pH
      optimum is 7.8-8.0, it requires a cation for activity and it displays
      cooperativity for ATP. The effect of various ATP analogs was analyzed.
      Determination of the molecular size of HisQMP2(his6) indicates that it is a
      monomer. The permeability properties of two kinds of reconstituted PLS
      preparations are described.

PMID- 11456222
TI  - Comparison of different cations (Mn2+, Mg2+, Ca2+) on the hydrolytic activity of
      chloroplast ATPase.
AB  - The influences of Mn2+, Mg2+, and Ca2+ on the enzymic activity of chloroplast
      ATPase have been compared, using an HPLC method for the separation of ADP. The
      dissociation constants of the divalent ion-ATP complexes have been determined by
      a spectrophotometric method, with the dye antipyrylazo III, and enzymic constants
      (dissociation constant of the ion-enzyme complexes, Michaelis constants, maximum
      rates) have been calculated. The comparison between the rates obtained,
      respectively, with Mn2+ and Ca2+ alone with that given by the mixture of these
      two ions, allows us to conclude that, as for Mg2+, Mn2+ is also an activator of
      chloroplast ATPase and that metal-free ATP is the true substrate.

PMID- 11456223
TI  - The carboxin-binding site on Paracoccus denitrificans succinate:quinone reductase
      identified by mutations.
AB  - Succinate:quinone reductase catalyzes electron transfer from succinate to quinone
      in aerobic respiration. Carboxin is a specific inhibitor of this enzyme from
      several different organisms. We have isolated mutant strains of the bacterium
      Paracoccus denitrificans that are resistant to carboxin due to mutations in the
      succinate:quinone reductase. The mutations identify two amino acid residues,
      His228 in SdhB and Asp89 in SdhD, that most likely constitute part of a carboxin
      binding site. This site is in the same region of the enzyme as the proposed
      active site for ubiquinone reduction. From the combined mutant data and
      structural information derived from Escherichia coli and Wolinella succinogenes
      quinol:fumarate reductase, we suggest that carboxin acts by blocking binding of
      ubiquinone to the active site. The block would be either by direct exclusion of
      ubiquinone from the active site or by occlusion of a pore that leads to the
      active site.

PMID- 11456224
TI  - The heterogeneity in risk factors of lung cancer and the difference of histologic
      distribution between genders in Taiwan.
AB  - OBJECTIVE: The difference in histologic patterns of lung cancer between men and
      women in Taiwan may be associated with the heterogeneity in causal factors of
      lung cancer between the sexes. A sex- and age-matched case-control study was
      designed to investigate such a relationship. METHODS: Cases consisted of 236 male
      and 291 female incident cases with newly diagnosed and histologically confirmed
      primary carcinoma of the lung, and were compared to one or two individually
      matched controls. RESULTS: Cigarette smoking, occupations, and previous
      tuberculosis history were found to independently correlate with an elevated risk
      of squamous/small cell carcinoma and adenocarcinoma for male patients. However,
      there was little difference in the effect of these risk factors except smoking.
      The use of fume extractors in the kitchen, and the habit of waiting to fry after
      the fumes were emitted, separately explained the majority of the attributable
      fraction of female squamous/small cell carcinoma (28.2%) and adenocarcinoma
      (47.7%). With the exception of a kitchen with fume extractors and a clinical
      history of tuberculosis, the environmental causal factors of lung cancer were
      heterogeneous between these two histologic cell groups. CONCLUSIONS: Our results
      suggested that the causal factors of lung cancer might be specific for the type
      of tumor concerned. The gender-specific risk factors of lung cancer could partly
      explain the difference in cell-type distribution between men and women.

PMID- 11456225
TI  - Pet ownership and childhood acute leukemia (USA and Canada).
AB  - OBJECTIVES: For more than three decades there has been speculation regarding a
      possible role of zoonotic diseases in the development of human leukemia. This
      study investigated the potential relationship between exposure to pets and the
      development of childhood leukemia. METHODS: Data from 2359 cases of acute
      leukemia from two large case-control studies were analyzed. Cases were
      individually matched to population controls on telephone exchange, age, and race.
      Conditional logistic regression was used to estimate odds ratios (OR) associated
      with pet ownership. RESULTS: Overall, there was no association between pet
      ownership (either "any pet", dog, or cat) and childhood acute leukemia (OR(any
      pet:) = 1.01, 95% CI 0.89-1.2). Additionally, no relationship was found between
      exposure to an ill pet and childhood leukemia. CONCLUSION: The results of this
      analysis suggest that pet ownership (healthy or sick) is unrelated to an
      increased risk of childhood leukemia.

PMID- 11456226
TI  - Evaluating the impact of population changes in diet, physical activity, and
      weight status on population risk for colon cancer (United States).
AB  - OBJECTIVE: To estimate the effects of observed population-level changes in risk
      factors on population risk and incidence of disease. METHODS: Trends in a set of
      risk factors for colon cancer (vegetable intake, red meat intake, alcohol
      consumption, physical activity levels, and weight status) were modeled for the US
      adult population over the years 1975-1995 and combined with relative risk
      estimates from epidemiologic studies and a probability distribution for the
      induction period to estimate the percentage change in incidence rates from 1985
      to 1995 due to the five risk factors. A sensitivity analysis was performed to
      account for imprecision related to estimates of trends in behavior and
      epidemiologic risk. RESULTS: Increased vegetable intake and decreased intakes of
      red meat and alcohol reduced risk, while reduced physical activity and increased
      body mass index increased risk for colon cancer. When all five factors were
      considered together, change in the average population relative risk was small and
      the risk factors accounted for little of the recently observed decline in
      incidence. CONCLUSIONS: Although these factors have the potential to greatly
      affect risk of colon cancer and incidence rates, little of that potential was
      realized since adverse trends neutralized what progress had been made in the
      areas of vegetables, red meat, and alcohol consumption.

PMID- 11456227
TI  - Elevated serum homocysteine levels and increased risk of invasive cervical cancer
      in US women.
AB  - OBJECTIVES: To explore the relationship between serum homocysteine, a sensitive
      biomarker for folate inadequacy and problems in one-carbon metabolism, and
      invasive cervical cancer. METHODS: A large case-control study was conducted in
      five US areas with up to two community controls, obtained by random-digit
      dialing, individually matched to each case. Cervical cancer risk factors were
      assessed through at-home interview. Blood was drawn at least 6 months after
      completion of cancer treatment from 51% and 68% of interviewed cases and
      controls. Serum homocysteine was measured by high-performance liquid
      chromatography, and exposure to human papillomavirus (HPV) type 16, the most
      prevalent oncogenic type, was assessed using an enzyme-linked immunosorbent
      assay. Cases with advanced cancer and/or receiving chemotherapy were excluded,
      leaving 183 cases and 540 controls. RESULTS: Invasive cervical cancer risk was
      substantially elevated for women in the upper three homocysteine quartiles (>
      6.31 micromol/L); multivariate-adjusted odds ratios ranged from 2.4 to 3.2 (all
      95% CIs excluded 1.0). A trend was apparent and significant (p = 0.01). When
      cases were compared with HPV-16 seropositive controls only, odds ratios were
      comparable. CONCLUSIONS: Serum homocysteine was strongly and significantly
      predictive of invasive cervical cancer risk. This association could reflect
      folate, B12 and/or B6 inadequacy, or genetic polymorphisms affecting one-carbon
      metabolism.

PMID- 11456228
TI  - Smoking and hematolymphopoietic malignancies.
AB  - OBJECTIVE: Tobacco use is the most prominent cause of respiratory cancers. Little
      is known, however, about the influence of smoking on hematolymphopoietic
      malignancies. To evaluate this relation, a population-based case-control study
      was carried out in 12 areas of Italy. METHODS: Detailed interviews on tobacco
      smoking habits were administered to 1450 non-Hodgkin's lymphoma (NHL), 365
      Hodgkin's disease (HD), 270 multiple myeloma (MM), and 649 leukemia (LEU)
      patients occurring from 1990 to 1993, and 1779 population controls. RESULTS: We
      found a slightly increased risk for NHL in smokers (odds ratio 1.2, 95%
      confidence interval 1.0-1.4 for ever smokers), but a consistent positive
      association was shown only for follicular NHL. In this subtype, a significant
      excess risk was observed for ever versus never smokers, after adjustment for
      gender, age, geographic residence, education, and respondent (OR = 1.8, 95%, CI
      1.3-2.7), with a positive exposure-response gradient for smoking duration (p <
      0.01). The risk for follicular NHL was significantly elevated only among women,
      with ever smokers showing OR = 2.3 (CI 1.4-3.8), while for men we found OR = 1.3
      (CI 0.69-2.3). No major differences were shown according to age. Female subjects
      also showed significant positive exposure-response trends for duration.
      CONCLUSION: Cigarette smoking could be a risk factor for follicular NHL among
      women. For HD, MM, or LEU, no clear association was observed.

PMID- 11456229
TI  - Prospective study of antibody to human papilloma virus type 16 and risk of
      cervical, endometrial, and ovarian cancers (United States).
AB  - OBJECTIVE: Human papilloma virus (HPV) is frequently detectable in cancers of the
      cervix, vagina, and vulva, but its role in endometrial and ovarian cancers is
      less certain. This analysis aimed to examine the association of presence of HPV
      type 16 (HPV-16) antibodies with subsequent risk of cervical, endometrial, and
      ovarian cancers. METHODS: In a prospective study enrolling over 15,000 pregnant
      women, pre-cancer sera from women who developed cervical (n = 83), endometrial (n
      = 34), and ovarian (n = 35) cancers were compared with sera from 172 control
      women frequency-matched by age group and race. RESULTS: HPV-16 seropositivity (OR
      = 2.0, 95% CI 1.0-3.4) was associated with cervical cancer, with the association
      more prominent for cancers occurring within 10 years of serum sampling (OR = 2.3,
      95% CI 1.0-5.3) than cancers occurring later (OR = 1.6, 95% CI 0.75-3.6).
      Overall, the associations between HPV-16 seropositivity and endometrial (OR =
      1.6, 95% CI 0.64-3.8) and ovarian cancers (OR = 1.1, 95% CI 0.43-2.8) were not
      significant, although the odds ratios for those cancers occurring within 20 years
      after serum sampling were similar to that for cervical cancer (OR = 2.2 for
      both). CONCLUSIONS: Our results confirm that HPV-16 infection precedes the
      development of cervical cancer. Predictability of HPV-16 seropositivity for risk
      of other female cancers warrants further investigation.

PMID- 11456230
TI  - Height and breast cancer risk: results from the Black Women's Health Study
      (United States).
AB  - OBJECTIVES: Numerous studies, but not all, have yielded positive associations
      between adult height and risk of breast cancer. There are few data on black
      women. We evaluated adult height in relation to breast cancer in data from the
      Black Women's Health Study, a prospective cohort study of 64,530 African-American
      women aged 18-69 years at baseline in 1995. METHODS: A total of 910 cases of
      breast cancer were analyzed: 700 prevalent cases reported at baseline and 210
      incident cases that occurred during the first 2 years of follow-up. A comparison
      group of controls frequency-matched on 5-year category of birth year was chosen
      from among participants who had not developed breast cancer. Odds ratios (OR)
      were calculated for various categories of adult height compared to a reference
      category of height less than or equal to 61 inches (155 cm), with control for
      current age, age at menarche, and years of education. RESULTS: Increased height
      was associated with an increased risk of breast cancer overall (p trend = 0.001);
      the OR for the highest category of height, > 69 inches (175 cm), was 1.6 (95%
      confidence interval 1.1-2.3). The association was stronger among premenopausal
      women and women who had less than 16 years of education. Results were similar for
      prevalent and incident cases. CONCLUSION: The present findings indicate that
      height is associated with breast cancer risk in African-American women.

PMID- 11456231
TI  - Association of family history and other risk factors with breast cancer risk
      among Japanese premenopausal and postmenopausal women.
AB  - OBJECTIVES: To determine the impact of family history (FH) on anthropometric and
      reproductive risk factors for breast cancer, a case-referent study was conducted
      using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer
      Center (HERPACC), Japan. METHODS: In total, 1584 breast cancer cases were
      included and 15,331 women, confirmed as free of cancer, were recruited as the
      referents. Odds ratios and 95% confidence intervals were determined by logistic
      regression analysis. Separate analyses were performed for premenopausal and
      postmenopausal women. RESULTS: Height, weight, and current body mass index (BMI)
      were positively associated with postmenopausal breast cancer regardless of FH,
      while these anthropometric factors did not alter risk in premenopausal women. The
      impacts of height and weight on postmenopausal breast cancer were more pronounced
      among FH women. There was little association with reproductive risk factors for
      premenopausal or postmenopausal breast cancer in FH cases, in clear contrast to
      the non-FH cases. CONCLUSIONS: These findings suggest some differences in risk
      impact of common etiologic factors between familial breast cancer and sporadic
      cases that may give pointers to further analysis of host-specific factors. They
      imply that avoidance of obesity after menopause may reduce the risk of breast
      cancer, regardless of FH.

PMID- 11456232
TI  - Variants of the VDR gene and risk of colon cancer (United States).
AB  - OBJECTIVES: Genetic factors involved in regulating cell growth, such as the
      vitamin D receptor (VDR) gene, may contribute to the etiology of colon cancer.
      METHODS: Using data from a population-based case-control study of colon cancer
      and from a family-based study of cases with colon cancer and population-based
      controls, we evaluated the association between four variants of the VDR gene and
      risk of colon cancer. RESULTS: The polyA (short), BsmI (BB), and TaqI (tt)
      variants of the VDR gene were in linkage disequilibrium in this mostly Caucasian
      population. These variants were associated with reduced risk of colon cancer (OR
      0.5, 95% CI 0.3-0.9). The FokI variant was not associated with colon cancer risk.
      Although estimates of association were imprecise, there were suggestions that
      associations were slightly stronger for women than men, for people diagnosed at a
      younger age, and for those with proximal tumors. Consistent associations were
      observed from sporadic cases of colon cancer from a population-based study as
      well as from colon cancer cases from a family-based study. There were no
      interactions observed by family history. CONCLUSIONS: These data suggest that
      molecular variants of the VDR gene may be related to the development of colon
      cancer. To further define the impact of the VDR gene on cancer etiology, studies
      to evaluate the association of these variants with diet and lifestyle factors are
      needed.

PMID- 11456233
TI  - Occupational exposure to diesel engine emissions and risk of cancer in Swedish
      men and women.
AB  - OBJECTIVE: To investigate the risk of cancer among workers exposed to diesel
      emissions in a large record-linkage study from Sweden. METHODS: The Swedish
      Cancer Environment Register III contains nationwide data on cancer incidence
      during 1971-1989, by occupation and industry of employment as reported in the
      1960 and 1970 censuses. After excluding farmers, we classified job and industry
      titles according to estimated probability and intensity of exposure to diesel
      emissions. Exposed men in the 1960 census contributed over 7,400,000 person
      years, and exposed women contributed over 240,000. We compared them to the
      remainder of the employed population, using indirect standardization and
      multivariate Poisson regression analysis. RESULTS: Men exposed in the 1960 census
      experienced an increased risk of lung cancer: the relative risks (RRs) were 0.95
      (95% confidence interval [CI] 0.9-1.0), 1.1 (1.1-1.2) and 1.3 (1.3-1.4) for low,
      medium, and high intensity of exposure. Corresponding results for probability of
      exposure were 1.1 (1.0-1.1), 0.9 (0.86-0.94) and 1.2 (1.1-1.2). The risk was
      higher for squamous cell carcinoma of the lung than for other histological types.
      Results in women were not suggestive of an effect (RR in the category of medium
      or high intensity of exposure 1.1, 95% CI 0.6-1.8). A small but significant
      increase in risk of cancers of the stomach (SIR 1.06), pancreas (SIR 1.05),
      larynx (SIR 1.09), and the kidney (SIR 1.06) was present among men exposed to
      diesel emissions, without a clear trend according to either probability or
      intensity of exposure. The SIR among women was non-significantly increased for
      stomach, pancreatic, and laryngeal cancers, but not for kidney cancer.
      Furthermore, a significantly increased risk of oral/pharyngeal (SIR 1.64) and
      cervical (SIR 1.48) cancers was present among women, with a suggestion of a dose
      response relationship. There was no increased risk of bladder cancer in either
      gender. CONCLUSIONS: The results of this study provide evidence of a positive
      exposure-response relationship between exposure to diesel emissions and lung
      cancer risk among men. The positive results for other neoplasms, such as stomach,
      pancreatic, oral/pharyngeal, and cervical cancers, cannot be attributed to diesel
      exposure, but they deserve attention in future investigations.

PMID- 11456235
TI  - Tobacco litigation: a mid-course review.

PMID- 11456234
TI  - A pooled analysis of case-control studies of thyroid cancer. VI. Fish and
      shellfish consumption.
AB  - OBJECTIVE: To better understand the role of fish and shellfish on thyroid cancer
      risk, we systematically re-analyzed the original data from 13 case-control
      studies conducted in the US, Japan, China, and Europe. METHODS: A total of 2497
      cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were
      considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were
      estimated for each study by logistic regression models, conditioned on age and
      sex, and adjusted for history of goiter, thyroid nodules or adenomas, and
      radiation. Combined ORs were computed as the weighted average of the estimates
      from each study. RESULTS: The ORs for the highest level of total fish consumption
      (three or more times per week) as compared to the lowest one (less than once per
      week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromso, and Vaud.
      Conversely, the ORs for the studies in Los Angeles. Shanghai, southeastern
      Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The
      pattern of risk for salt water fish and shellfish was not substantially different
      from that of total fish. Fish was not associated with thyroid cancer risk in all
      studies combined (OR = 0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI
      0.71-1.1 for high total fish consumption), but there was a suggestion of a
      protective effect in endemic goiter areas (OR = 0.65, 95% CI 0.48-0.88).
      CONCLUSION: This combined analysis indicates that relatively elevated fish
      consumption does not appreciably increase thyroid cancer risk, and may have a
      favorable influence in areas where iodine deficiency is, or was, common.

PMID- 11456236
TI  - Are grades helpful as a recruiting tool?

PMID- 11456237
TI  - General medicine as an independent specialty and holistically oriented scientific
      discipline.

PMID- 11456238
TI  - Value of a family medicine preceptorship/clerkship to students, preceptors, and
      communities: observations from a 25-year-old program.

PMID- 11456239
TI  - Ask the animals, and they will teach you.

PMID- 11456240
TI  - Poetry, mindfulness, and medicine.

PMID- 11456241
TI  - Obtaining prescribed CME credit at STFM national meetings: observations and
      suggestions. Society of Teachers of Family Medicine.

PMID- 11456242
TI  - Comparison of a family practice teaching service and a hospitalist model: costs,
      charges, length of stay, and mortality.
AB  - BACKGROUND AND OBJECTIVES: One third of our nation's health care costs are
      incurred in the hospital. This study compares the inpatient outcomes between a
      family practice teaching service (FPTS) and a hospitalist group in the same
      suburban community hospital. METHODS: All patients discharged by the hospitalist
      group or the FPTS between April 1998 and June 1999 were included for study if
      they had one of the 10 most frequent principal diagnoses on discharge. The
      outcomes compared between the groups were length of stay, mortality, total
      charges, laboratory charges, radiology charges, and direct costs. Student's t
      test, chi-square, and analysis of variance were used to compare the outcomes,
      after adjusting data for severity of illness. RESULTS: Mean severity of illness
      for the FPTS patients was 2.42 and for the hospitalist patients was 2.26, with
      higher scores indicating greater severity of illness. After adjusting for
      severity of illness, there were no differences between the two groups of
      physicians for total charges, laboratory charges, radiology charges, direct
      costs, length of stay, or mortality rates. CONCLUSIONS: This study failed to
      demonstrate a statistically significant difference in the use of hospital
      resources between a family practice residency teaching service and a hospitalist
      team. Given the outcomes measured in this community teaching hospital, the
      residency teaching service appears to be a financially competitive model for
      delivery of inpatient care.

PMID- 11456243
TI  - Use of a template to improve documentation and coding.
AB  - BACKGROUND AND OBJECTIVES: Accurate assignment of evaluation and management (E&M)
      codes is a challenge for physicians. Having guidelines close at hand during
      patient visits might improve appropriateness and accuracy of E&M coding. We
      developed a template based on a clinical prediction rule for group A beta
      hemolytic streptococcal (GABHS) pharyngitis to improve documentation and coding
      decisions. METHODS: Fifty office visits for sore throat were documented using
      templates and were compared with 50 sore throat visits that were documented using
      progress notes. We counted history and physical examination items and compared
      the level of service charged to the level of service supported by the note.
      RESULTS: Significantly more history of present illness and physical examination
      items were recorded on templates. Decisions related to treatment for patients
      with a low probability of GABHS were also improved by the templates. Templates
      had no effect on billing and coding errors. CONCLUSIONS: The template resulted in
      more-thorough documentation but had no effect on coding and billing errors
      relative to progress notes.

PMID- 11456244
TI  - Time and money: effects of no-shows at a family practice residency clinic.
AB  - BACKGROUND: When patients fail to appear for scheduled appointments, the flow of
      patient care is interrupted, and clinic productivity declines. This study
      investigated the impact of failed appointments on a clinic by measuring time and
      money lost after taking into account same-day treatment patients (walk-ins).
      METHODS: Schedule information was retrieved for 4,055 visits over 20 business
      days. Data were collected on appointment status (show, no-show, cancel, walk-in),
      time allocated for the appointment, charges for visit, date and time of the
      visit, and other appointment information. RESULTS: No-shows and cancellations
      represented 31.1% of scheduled appointments and 32.2% of scheduled time. Rates of
      failed appointments varied by type of provider, patient demographics, and patient
      status (new versus established). Walk-in patients replaced 61.0% of failed
      appointments but only 42.4% of the time blocked for those appointments. Walk-in
      visits generated 89.5% of the charges associated with scheduled visits. Over the
      course of a year, total revenue shortfalls could range from 3% to 14% of total
      clinic income. CONCLUSIONS: Failed appointments pose financial as well as
      administrative problems for residency practices. Proactive reminder systems are
      needed to promote patient attendance.

PMID- 11456245
TI  - Speaking and interruptions during primary care office visits.
AB  - BACKGROUND: Patients and physicians value effective communication and consider it
      an essential part of the medical encounter. This study examined physician-patient
      communication patterns, and interruptions in communication, during patient visits
      with family practice and internal medicine residents. METHODS: Observational data
      obtained from 60 routine primary care office visits included the time that
      resident physicians and patients spoke and the number and types of interruptions.
      A total of 22 family practice and internal medicine residents participated, 9
      from family practice and 13 from internal medicine. RESULTS: Patients spoke,
      uninterrupted, an average of 12 seconds after the resident entered the room. One
      fourth of the time, residents interrupted patients before they finished speaking.
      Residents averaged interrupting patients twice during a visit. The time with
      patients averaged 11 minutes, with the patient speaking for about 4 minutes.
      Computer use during the office visit accounted for more interruptions than
      beepers. Verbal interruptions, a knock on the door, beeper interruptions, and
      computer use all interfered with communication, and increased frequency of
      interruptions are associated with less favorable patient perceptions of the
      office visit. Female residents interrupted their patients less often than did
      male physicians. All residents interrupted female patients more often than male
      patients. Early and increased interruptions were associated with patients'
      perception that they should have talked more. Third-year residents interrupted
      patients less frequently than did first-year residents. CONCLUSIONS: Numerous
      interruptions occurred during office visits. Gender was associated with the
      pattern of interruptions. Physicians frequently interrupted patients before the
      patients were finished speaking. Computer use also interrupted physician-patient
      communication.

PMID- 11456246
TI  - Improving clinic efficiency of a family medicine teaching clinic.
AB  - BACKGROUND: Teaching clinics are the heart of training programs in family
      practice. It is in these training clinics where residents develop their
      ambulatory practice habits. Yet, little is known about the efficiency of these
      teaching clinics. METHODS: We conducted a time-and-motion study of patient flow
      in a residency teaching clinic. RESULTS: During each half-day session, 7.8 +/-
      1.9 providers were scheduled in clinic, and 55.5 +/- 12.9 patients were seen.
      First-year residents saw 3.55 patients per half-day session, second-year
      residents saw 4.75 patients, third-year residents saw 8.0 patients, faculty saw
      8.22 patients, and urgent care saw 8.35 patients. The number of patients
      scheduled was highly correlated with the number of providers in clinic. Of the
      patients scheduled, 25% failed to keep their appointment, and 31% arrived late.
      Neither rates of no-show patients nor rates of late patients varied by level of
      provider. The mean time patients spend in the clinic was 80.5 +/- 30 minutes,
      with 17 +/- 10 minutes spent registering, 18 +/- 17 minutes spent being roomed,
      and 19 +/- 16 minutes spent waiting for the provider. The physician spent 27 +/-
      16 minutes with the patient, including both face-to-face time and precepting
      time. Patients who arrived on time waited significantly longer than those who
      arrived late. Waiting time did not vary significantly by level of physician. The
      time patients spent with their doctor did vary significantly by level of
      physician; first-year residents spent more time with their patients than upper
      level residents or faculty. CONCLUSIONS: Significant variation exists in the
      patient flow through the clinic. Patient volumes are significantly correlated to
      the number of providers in clinic. Long waiting times are due in part to long
      processing times and in part to long waits in the exam room. Concerted
      multidimensional efforts are needed to smooth out patient flow and improve clinic
      efficiency.

PMID- 11456247
TI  - Non-penetrating deep sclerectomy and collagen implant surgery in glaucoma
      patients with advanced field loss.
AB  - PURPOSE: The aim of the study was to determine the medium term intraocular
      pressure (IOP) lowering effects and the potential complications of non
      penetrating deep sclerectomy and collagen implant (DSCI) surgery in glaucoma
      patients. PATIENTS AND METHODS: 54 eyes of 52 patients with medically
      uncontrolled open angle glaucoma with advanced field loss underwent DSCI under
      topical anaesthesia. Follow-up period was 24 months. RESULTS: The mean
      preoperative IOP was 24.7 +/- 6.2 mmHg and decreased to 15.1 +/- 4.0 mmHg at 24
      months (p = 0.0068). During the follow- up period, 36 of 54 eyes (66%) received
      no topical antiglaucomatous medications. In 18 eyes, monotherapy with topical
      beta blockers (Betaxolol HCl) was added to the regimen. At last visit, only two
      patients (3.8%) had IOP greater than 18 mmHg. We did not detect any additional
      optic disc changes, visual field or visual acuity defects postoperatively.
      Detailed slit-lamp examination revealed no anterior segment complications
      regarding the probable complications of trabeculectomy. None of the patients
      developed surgery related cataract. As a complication, we diagnosed one case of
      self-limited, shallow choroidal detachment. CONCLUSION: DSCI appears to provide
      considerable medium term IOP decrease with few postoperative complications
      without deteriorating visual acuity. Owing to our medium term results, we believe
      that DSCI could be a valuable alternative to trabeculectomy especially in cases
      of advanced medically uncontrolled open angle glaucoma.

PMID- 11456248
TI  - Bilateral angle closure glaucoma following general anesthesia.
AB  - Although unilateral angle closure glaucoma is quite common, simultaneous
      bilateral acute angle closure is very rare and is usually induced by an external
      cause. General anesthesia is a triggering factor for acute angle closure
      glaucoma. We report two cases of simultaneous bilateral angle closure glaucoma
      following non-ocular surgery under general anesthesia. One patient had
      cholecystectomy, the other craniotomy for tumor resection. In the postoperative
      period following general anesthesia, any patient at risk for angle closure
      glaucoma should be followed closely; patients with periorbital pain and visual
      symptoms should be examined for angle closure glaucoma attack in both eyes.

PMID- 11456249
TI  - Acute corneal decompensation after silicone oil removal.
AB  - PURPOSE: To assess acute corneal decompensation after silicone oil removal in
      some aphakic eyes with clear corneas whose anterior chambers were completely
      filled with silicone oil for a considerable period of time. METHODS: Eight eyes
      of 8 patients who underwent vitrectomy and intraocular silicone oil injection
      were studied. All the eyes were aphakic and anterior chambers were completely
      filled with silicone oil. In all eyes, corneas were clear and no corneal finding
      indicating keratopathy was detected by slit-lamp microscopy before silicone oil
      removal. The mean silicone oil removal time was 4 months (range 2-7 months). A
      specular microscope was used for the evaluation of corneal endothelial changes
      and corneal pachometry was performed to observe corneal changes before and after
      the silicone oil removal in 5 eyes besides slit-lamp microscopy. The follow up
      period after silicone oil removal was 2-12 months (mean 6 months). RESULTS: In
      all eyes severe corneal stromal edema and clouding was detected in the first day
      following silicone oil removal. Increased corneal thickness was seen in all eyes.
      Decreased (at or below critical levels) corneal cell density was detected by
      specular microscopy before and after silicone oil removal. No significant
      improvement was observed during the follow up period. CONCLUSION: Eyes whose
      anterior chambers completely filled with silicone oil could be evaluated as clear
      corneas by slit lamp microscopy despite severe endothelial damage. We recommend
      that eyes with silicone oil in the anterior chambers should be monitored by a
      combination of slit-lamp microscopic examination and specular microscopy to
      determine the relative corneal endothelial tolerance to the silicone oil and
      endothelial damage. Early removal of the silicone oil can be considered when the
      retinal adhesion allows.

PMID- 11456250
TI  - Immunocytochemical features of lens after cataract tissue--signalling molecules
      (growth factors, cytokines, other signalling molecules), cytoskeleton proteins,
      cellular and extracellular matrix proteins.
AB  - We examined the immunocytochemical features of after cataract tissue and
      cataractous lens epithelium prior to cataract surgery and at the time of surgery.
      METHODS: This study included 23 cases. Antibodies against the following antigens
      were used: epidermal growth factor (EGF), EGF receptor (EGF-R), fibroblast growth
      factor (FGF), FGF receptor (FGF-R), transforming growth factor (TGF)-beta, TGF
      beta receptor II (TGF-beta -RII), insulin-like growth factor (IGF)II, platelet
      derived growth factor (PDGF)-AB, interleukin (IL)-6, IL-1 receptor II, tumor
      necrosis factor (TNF)-alpha, tissue plasminogen activator (TPA), prostaglandin
      (PG) E2, plasminogen activator inhibitor (PAI)-1, alpha smooth muscle actin
      (alpha-SMA), keratin, vimentin, myosin, fibronectin, laminin, types I, II, III,
      IV, V and VI collagen (Col), and lens epithelial cells (LECs). RESULTS: The
      following substances were present in posterior and anterior capsular fibrosis of
      after cataract: EGF, EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, PDGF-AB,
      IL-6, IL-1RII, TNF-alpha, PGE2, PAI-1, alpha-SMA, keratin, fibronectin, laminin,
      Type I col, Type II to VI col and LECs. Elschnig's pearls of after cataract
      expressed FGF-R, TNF-alpha, laminin and LECs. Soemmering's ring of after cataract
      tissue expressed EGF, FGF, FGF-R, IL-1RII, TPA, PAl-1, keratin and LECs. The
      following substances were present in cataractous lens epithelium prior to
      cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-beta-RII, IL-1-RII, TNF-alpha, PAI
      1, keratin, laminin and LECs. The following substances were present in the lens
      epithelium of anterior capsules collected at the time of cataract surgery: EGF,
      EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, IL-6, IL-1-RII, TNF-alpha,
      PGE2, keratin, fibronectin, laminin, Type IV Col and LECs. CONCLUSIONS: These
      results prove that many kinds of signalling molecules and proteins exist in the
      process of after cataract formation.

PMID- 11456251
TI  - Management of traumatic retinal detachment with vitreon in children.
AB  - PURPOSE: To report the use of perfluoroperhydrophenanthrene (vitreon) for
      traumatic retinal detachment in children. METHODS: Vitreon was used as an
      intraoperative adjunct in 34 children with complicated retinal detachment
      secondary to penetrating and perforating trauma. The characteristics of the
      injuries, the final visual acuities, the postoperative complications and the rate
      of anatomic success were evaluated in a retrospective study. RESULTS: Patients
      were followed-up an average of 20 months. Eighteen retinas (53%) were reattached,
      and the postoperative visual acuity was counting fingers or better in 9 cases
      (26%), and only 4 eyes saw better than 10/200 at last follow-up. Hypotony
      developed in 7 (21%) of 34 eyes. CONCLUSION: Management of traumatic retinal
      detachment in children is difficult. Vitreon, as other perfluorocarbons, may be
      an effective intraoperative tool for vitreoretinal surgery in pediatric eyes that
      suffer trauma.

PMID- 11456252
TI  - Influence of betaxolol and timolol on the venous tone in glaucoma patients.
AB  - The aim of this study was the assessment of physiological venous reflexes in 40
      glaucoma patients treated with topically applied timolol maleate 0.50% and
      betaxolol HCL 0.50%. They were divided into two groups of twenty each; one group
      being given timolol and the other betaxolol. The assessment of the venous tone
      was performed by testing venous reflexes. We found no statistically significant
      difference between timolol and betaxolol; however, when the influence of
      circulating catecholamines and the other vasoactive substances was excluded by
      suprasphygmatic insufflation of a pediatric cuff, a significant difference was
      found in the Valsalva's maneuver (125.5 +/- 8.1 vs 85.0 +/- 34.3 venoconstrictive
      units VCUs, p = 0.03). The IOP was significantly decreased in both treatment
      group, although the pressure reduction effect was more pronounced in the timolol
      group. Our study suggests that timolol and betaxolol have a slightly different
      mode of action on the venous side of circulation under topical medications. It is
      possible that the use of betaxolol topically may reduce a systemic
      venoconstriction.

PMID- 11456253
TI  - Genetic thrombophilia in patients with retinal vascular occlusion.
AB  - BACKGROUND: This study was carried out to determine the prevalence of genetic
      thrombophilia in patients with retinal vascular occlusion. METHODS: We
      investigated 116 consecutive patients with central retinal vein occlusion (CRVO,
      n = 48), branch retinal vein occlusion (BRVO, n = 33), central retinal artery
      occlusion (CRAO, n = 21), branch retinal artery occlusion (BRAO, n = 14). All
      patients underwent comprehensive tests for coagulation disorders including
      determinations of protein C, protein S, lupus anticoagulants, prothrombin gene
      mutation (G20210A), resistance to activated protein C (APCR), and were screened
      for vascular disease risk factors. APC resistance was confirmed by a PCR method
      to detect the factor V R506Q mutation. A PCR method was also used to detect the
      G20210A mutation. For comparative purposes, we screened 209 consecutive patients
      with deep vein thrombosis (DVT) and 581 patients with coronary heart disease
      (control group) for APC resistance. RESULTS: 13 (27%) of 48 patients with CRVO
      had the factor V R506Q mutation. The factor V R506Q mutation was detected in six
      (18%) of 33 patients with BRVO, but in only one patient with CRAO and in two
      patients with BRAO. Other thrombophilic defects were not detected. The APCR
      prevalence within the CRVO group was significantly increased when compared to the
      control group (8%). There was no significant difference in the factor V R506Q
      mutation prevalence between the CRVO group and the DVT group (19%). CONCLUSION:
      The factor V R506Q mutation is the most common cause of genetic thrombophilia in
      patients with CRVO and has a similar prevalence as in DVT patients.

PMID- 11456254
TI  - Bilateral penetrating keratoplasty--indications, results and review of
      literature.
AB  - PURPOSE: To analyze the indications, functional results, and rates of graft
      rejection and failure after bilateral penetrating keratoplasty (PK) in a major
      eye care hospital and research center in India. METHODS: Retrospective review of
      the case records of 38 patients who underwent bilateral PK and had at least 6
      months follow-up after corneal transplantation in the second eye. RESULTS: The
      mean age of the 38 patients (20 M, 18 F) was 35 +/- 25 years (range, 0.5 to 79
      years). Mean follow-up was 49 +/- 23 months (range, 13.4 to 116.4 months) after
      surgery in the first eye and 31 +/- 22 months (range, 6.6 to 103.6 months) after
      surgery in the second eye. The average time interval between surgery in the first
      and second eye was 18 +/- 10 months (range, 0 to 38 months). The commonest
      indications for surgery were corneal dystrophies (50%), aphakic bullous
      keratopathy (21%), and keratoconus (11%). Postoperatively, secondary glaucoma
      occurred in 2 first and 3 second eyes. Best-corrected visual acuity at last
      follow-up was > 6/12 in 34% of first eyes and 50% of second eyes, and was < 6/60
      in 26% and 18% of first and second eyes respectively. Allograft rejection
      occurred in 4 of the first eyes and 3 of the second eyes. The two-year graft
      survival rate in first eyes was 70% and in second eyes was 83%. Worse outcomes
      were noted in grafts performed for secondary endothelial failure. Earlier graft
      failure occurred in first eyes (54 +/- 5 months) compared to second eyes (79 +/-
      10 months) (Logrank Test p = 0.2311). CONCLUSIONS: Bilateral penetrating
      keratoplasty has reasonable success in selected patients. Corneal transplantation
      in the second eye does not seem to increase the risk of graft rejection in either
      eye.

PMID- 11456255
TI  - Cerebellar astrocytoma presenting with acute esotropia in a 5 year-old girl. Case
      report.
AB  - We encountered a 5-year-old girl with acute onset of alternating, comitant
      esotropia in the absence of diplopia and other neurologic findings. She did not
      have any refractive error and seen bilateral papilledemas in fundus examination,
      magnetic resonance imaging (MRI) of the head was performed. A large cerebellar
      astrocytoma and moderate hydrocephalus was identified and successfully resected.
      The onset of comitant esotropia in a child can be the first sign of a cerebellar
      tumor without any other neurologic signs and symptoms.

PMID- 11456256
TI  - Determination of dopamine D1 receptors in the human uveo scleral tissue by light
      microscope autoradiography.
AB  - The aim of this paper is to clarify the distribution of Dopamine D1 (DA D1)
      receptors in the uveo-scleral tissue of human eyes with or without elevated
      intraocular pressure (IOP) and to study the relationships between DA D1 receptors
      and uveo-scleral tissue. Samples of human uveo-scleral tissue were taken from
      seven men undergoing eye surgery for a traumatic lesion of the anterior segment
      of the eye, without involvement of the iris-corneal angle and /or from eye
      donors. The subjects (in whom one eye bulb had been surgically enucleated) had
      been previously enrolled in our medical protocols because they suffered for
      increased IOP, while the eye donors (of both eye bulbs) had a normal IOP. Frozen
      sections from the uveo-scleral tissue were submitted to biochemical
      characterization and to morphological autoradiographic techniques for detection
      of DA-D1 receptors. [3H]-SCH-23390 was used as a ligand of Dopamine D1 receptors.
      [3H]-SCH 23390 was bound by sections of the human uveo-scleral tissue. The
      pharmacological profile of the binding was consistent with the labeling of D1
      receptors. Light microscope analysis was used for localization of D1 receptors
      and revealed an accumulation of the radioligand in the human uveo-scleral tissue.
      In eyes with normal IOP there is a high reaction. The Bmax of radioligand
      decreases in the eyes with increased IOP. The possibility that dopaminergic
      receptors play a role in the controlling uveo-scleral tissue functions is
      suggested.

PMID- 11456257
TI  - Roles and mechanisms of action of pituitary adenylate cyclase-activating
      polypeptide (PACAP) in growth hormone and prolactin secretion.
AB  - It appears that PACAP has a direct action on somatotrophs to release GH. The
      intracellular signal transduction mechanisms for PACAP might be similar to but
      partly distinct from those for GRH. PACAP might play a role in GH secretion
      induced by serotoninergic mechanisms but not in ultradian rhythm of GH secretion
      in the rat. PACAP can stimulate PRL release from the pituitary in rats possibly
      through indirect paracrine effect. In addition, PACAP might participate in
      regulation of PRL secretion via hypothalamic VIP.

PMID- 11456258
TI  - Final height and growth hormone secretion after bone marrow transplantation in
      children.
AB  - Growth hormone (GH) deficiency has been regarded as a principal determinant for
      growth failure following bone marrow transplantation (BMT). We herein analyzed
      final height and GH secretion in the patients who received BMT during childhood.
      The study on final height in 30 patients (23 males; 19 with malignant disease)
      who underwent BMT before or at the onset of puberty showed the following
      findings: (1) Final height SD score (SDS) significantly decreased compared to
      pretreatment height SDS. (2) Patients who underwent BMT before the age of 10
      years showed significantly greater reduction in height SDS compared to those who
      received after the age of 10 years. (3) The type of disease or a difference in
      preconditioning regimen did not influence the outcome of growth. (4) No patient
      showed GH deficiency. The study on GH secretion included 71 patients who had been
      followed for more than 5 years and who underwent insulin tolerance test more than
      twice following BMT. Thirteen patients experienced poor GH response at least
      once. Two of these patients had poor GH response repeatedly. In conclusion,
      children who undergo BMT at younger age have a higher risk of growth failure, and
      GH deficiency is not a major contributing factor for growth impairment following
      BMT.

PMID- 11456259
TI  - Induction of autoimmune hypothyroidism and subsequent hyperthyroidism by TSH
      receptor antibodies following subacute thyroiditis: a case report.
AB  - A 45 year-old man had a typical episode of subacute thyroiditis with tender
      goiter, depressed radioiodine uptake (RAIU) and elevated erythrocyte
      sedimentation rate. The titer of TSH binding inhibitor immunoglobulin (TBII),
      which had been 8.6% at initial presentation, rose to 14.9% in 2 weeks. TBII
      consisted of high titers (94%) of TSH stimulation-blocking antibodies (TBAb) and
      negative thyroid stimulating antibodies (TSAb). About 2 months after the first
      visit, TBII titers had risen to 48.9% and were persistently elevated for 5 months
      with high TBAb activity. The patient developed hypothyroidism with a maximum
      serum TSH level of 54.5 microU/ml. TBII and TBAb titers then gradually decreased,
      and the patient spontaneously recovered from hypothyroidism. Eighteen months
      after the episode of subacute thyroiditis, he became hyperthyroid with elevated
      TSAb and negative TBAb values. Doppler ultrasonography showed increased blood
      flow in the thyroid, and RAIU at 24 h was 53%. He was treated with antithyroid
      drugs, and soon became euthyroid. This case indicates that subacute thyroiditis
      can induce thyroid autoimmunity, and that the character of TSH receptor
      antibodies (TSHRAb) in these patients can change thereby modifying their thyroid
      function.

PMID- 11456260
TI  - Analysis of the KAL1 gene in 19 Japanese patients with Kallmann syndrome.
AB  - Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism
      and anosmia. The KAL1 gene is responsible for the X-linked form of Kallmann
      syndrome. We analyzed the KAL1 gene in 19 Japanese patients with Kallmann
      syndrome, including 3 patients reported previously, using PCR-direct sequencing
      method. All of 19 patients were sporadic, except for 2 monozygotic twins. In this
      study, there were 3 kinds of mutations in the KAL1 gene. One of them was a novel
      mutation consisting of a G to A substitution in the acceptor site at the junction
      of intron 6/exon 7. None of the mutations have been reported in countries other
      than Japan. In male sporadic patients with Kallmann syndrome, the incidence of
      mutations in Japanese patients (14%: 2 of 14 cases) was slightly higher than that
      in patients in USA (8%). Also, we found 2 polymorphisms, which were always found
      together in 6 patients. The severity of hypogonadism was not related to the
      presence of mutations. Unilateral renal aplasia and mirror movement, which are
      frequently found in patients with the KAL1 gene mutation, were not related to the
      sites of mutations.

PMID- 11456261
TI  - Clinical differences between benign and malignant pheochromocytomas.
AB  - Most pheochromocytomas can be cured by resection. In view of the unfavourable
      prognosis for surgical therapy in cases of late tumour detection and malignant
      tumours, the aim of the present study is to differentiate between typical signs
      and symptoms of malignant versus benign pheochromocytomas. We investigated the
      records of 133 patients retrospectively (1967-1998). In cases of benign tumours
      (104 of 133, mean age 42+/-15.8 years) tumour size was 5.9+/-3.4 cm, and history
      was 47.4+/-75.4 months. 7.7% of the tumours were extraadrenal, and 77% had
      paroxysmal manifestations. The other 29 patients (mean age: 39.2+/-21.9 years)
      had malignant lesions (tumour size: 9.4+/-5.9 cm (p=0.0022); history: 7.4+/-5.6
      months (p=0.0137); extraadrenal: 24.1% (p=0.0219); paroxysmal: 37.9% (p=0.0012)).
      Symptoms of patients with benign tumours were hypertension (80%), headaches
      (42.3%), sweating (30.8%), tachycardia (26%) and pallor (24%) (Malignant:
      Hypertension 46%, p=0.0873; headaches 11%, p=0.0008; sweating 11%, p=0.0196;
      tachycardia 14%, p=0.1961 and pallor 0%, p=0.0010). Abdominal pain and dorsalgia
      occurred more frequently in malignant pheochromocytomas (26% versus 7%,
      p=0.0014). Unusually short histories and extraadrenal localization appear to be
      suspicious for malignancy. The "typical" clinical signs and symptoms occur more
      frequently in patients with benign tumours and can therefore be regarded as
      typical signs of benign pheochromocytomas.

PMID- 11456262
TI  - Evidence for the presence of keratinocyte growth factor (KGF) in human ovarian
      follicles.
AB  - The presence of keratinocyte growth factor (KGF) in human follicular fluid (FF)
      was investigated in a total of 145 FFs obtained during oocyte retrieval for in
      vitro fertilization (IVF) from 29 patients with no apparent endocrine disorders.
      The concentrations of KGF, estradiol, progesterone, testosterone and human
      chorionic gonadotropin (hCG) in FF were measured by enzyme-linked immunosorbent
      assay. FF samples contained relatively higher amounts of KGF (2194+/-87 pg/ml),
      whereas its concentrations in serum were below assay limit (<31.2 pg/ml).
      Concentrations of KGF in FF were positively correlated with both progesterone
      (r=0.311, p<0.0005) and testosterone (r=0.230, p<0.01) concentrations in FF.
      However, KGF concentrations were not significantly correlated with estradiol and
      hCG concentrations. KGF in FF was detected as a broad band (26-29 kD) by
      immunoblotting, the size being reduced by 7kD after N-glycosidase treatment. In
      an in vitro experiment, KGF suppressed the basal and hCG-stimulated progesterone
      production by cultured human luteinized granulosa cells. summary, we demonstrated
      the presence of KGF in human ovarian follicles, suggesting its possible role as a
      local factor in regulating human ovarian functions.

PMID- 11456263
TI  - Analysis of cortisol secretion in hormonally inactive adrenocortical
      incidentalomas: study of in vitro steroid secretion and immunohistochemical
      localization of steroidogenic enzymes.
AB  - Adrenal incidentalomas have recently increased in incidence, and thus it has
      become important to establish clinical management of these patients. It is also
      important to evaluate whether these tumors are different from preclinical or
      overt Cushing's syndrome in their steroidogenesis. In this study, we therefore
      examined steroidogenesis of hormonally inactive adrenal incidentalomas via short
      term culture of tumor specimens, in addition to an immunohistochemical study of
      steroidogenic enzymes. Five patients (two men and three women) diagnosed with
      adrenocortical incidentaloma without any clinical signs of adrenocortical
      hormonal excess except for hypertension and disturbed glucose tolerance, were
      recruited for this study. Hormonal findings, including circadian rhythms for
      cortisol and ACTH secretion, the response of ACTH to CRH infusion and results of
      dexamethasone suppression test were all within normal limits in these patients.
      Immunoreactivity for all steroidogenic enzymes involved in cortisol production
      was detected in tumor cells in all cases examined. Results of in vitro
      steroidogenesis analysis using short-term culture revealed that levels of
      cortisol secretion varied among the cases. There were no differences in the
      immunolocalization of steroidogenic enzymes and/or the levels of cortisol
      secretion between these hormonally inactive tumors and preclinical and/or overt
      Cushing's syndrome. Dehydroepiandrosterone-sulfotransferase (DHEA-ST)
      immunoreactivity in nonneoplastic regions was suppressed in one case in which the
      tumor secreted cortisol similar to preclinical and/or overt Cushing's syndrome.
      These results demonstrate that the levels of in vitro steroid production and/or
      the immunolocalization of steroidogenic enzymes in hormonally inactive
      adrenocortical tumors vary markedly and are not overtly different from those of
      preclinical and/or overt Cushing's syndrome.

PMID- 11456264
TI  - A case of pulmonary metastatic thyroid cancer complicated with Graves' disease.
AB  - We report a case of pulmonary metastatic thyroid carcinoma complicated with
      Graves' disease. A 56-year-old Japanese woman was referred to the Niigata Cancer
      Center Hospital for isotope therapy for pulmonary metastatic thyroid carcinoma.
      In 1993, she received a left-hemithyroidectomy. In 1999, the remnant thyroid was
      resected for isotope therapy of metastatic lesions in the lungs. Although she had
      been receiving suppressive therapy with levothyroxine, her general condition was
      good, and TRAb was positive before the operation. After a total thyroidectomy,
      the patient became thyrotoxic. For functioning metastatic lesions, the patient
      was treated with 5550 MBq of 131I and methimazole. Thyroid function was
      normalized after the therapy but TRAb and TSAb levels remained high.

PMID- 11456265
TI  - Morning granulocytopenia in a case of Graves' disease.
AB  - A 65-year-old woman with Graves' disease presented marked diurnal changes in
      white blood cell (WBC) and granulocyte counts. Granulocyte count was low and
      sometimes decreased to 0.2-0.3 x 10(9)/l in the early morning and increased in
      the afternoon irrespective of her thyroid status. She did not develop sore throat
      or fever during the investigation period. The present study indicates that these
      unusual diurnal changes in WBC and granulocyte counts should be considered in the
      differential diagnosis of agranulocytosis in Graves' disease patients treated
      with an antithyroid drug.

PMID- 11456266
TI  - Detection of antipituitary antibodies in patients with autoimmune thyroid
      disease.
AB  - The aim of the present study was to investigate the prevalence of antipituitary
      antibodies (APA) in patients with autoimmune thyroid disease as determined by
      Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Results by
      Western blot analysis showed positivity for APA in serum of 22.4% of patients
      with Graves' disease (n=143, p<0.05) and 18.5% of patients with Hashimoto's
      thyroiditis (n=54, p<0.05), which were significantly higher than 6.2% in healthy
      controls (n=97). Similar results were obtained with ELISA. The titers of APA
      measured by ELISA (APA/ELISA) remained unchanged before and after therapy with
      antithyroid drug for Graves' disease, while thyrotropin-binding inhibitor
      immunoglobulins (TBII) decreased significantly. Similarly, no changes in APA by
      Western blot analysis were observed after therapy. In patients with Graves'
      disease, APA were not associated with thyroid status. There was no difference in
      APA between patients with positive and negative thyroid autoantibodies. A
      significant but weak positive correlation between APA/ELISA and anti-human GH
      measured by ELISA (anti-hGH/ELISA) was observed in patients with Graves' disease
      (r=0.601 p<0.001) and Hashimoto's thyroiditis (r=0.428 p<0.005). These findings
      have demonstrated the existence of APA detected by Western blot analysis and
      ELISA in some cases of autoimmune thyroid disease. The present results suggest
      that hGH and other antigens may be involved in APA in patients with Graves'
      disease and Hashimoto's thyroiditis.

PMID- 11456267
TI  - Effects of heat exposure on adrenergic modulation of insulin and glucagon
      secretion in sheep.
AB  - The effects of heat exposure on the adrenergic modulation of pancreatic secretion
      were investigated. Five ewes fed at maintenance level (ME base) were housed in
      thermoneutral (TN; 20 degrees C) and hot (30 degrees C) environments. Heat
      exposure caused an increase in respiration rate and a slightly higher rectal
      temperature, and decreases in basal insulin and glucose concentrations. Infusions
      of saline plus epinephrine caused increases in glucagon and glucose
      concentrations, and no significant change in insulin secretion. Phentolamine (an
      adrenergic alpha-antagonist) plus epinephrine augmented insulin secretion;
      however, this insulin secretory response was inhibited by heat exposure.
      Propranolol (a beta-antagonist) plus epinephrine produced a slight decrease in
      insulin secretion in the TN environment, whereas no effect was observed during
      heat exposure. While glucagon secretion through alpha-adrenergic stimulation was
      not affected by heat exposure, homeostatic signals controlling insulin release
      seemed to be affected during heat exposure. We thus hypothesised that insulin
      concentration is decreased in sheep fed at maintenance level in hot environments,
      and that this response is mediated in part by a modulation of beta-adrenergic
      function.

PMID- 11456268
TI  - Somatic gene alteration of AIB1 gene in patients with breast cancer.
AB  - AIB1 (amplified in breast cancer 1) is a coactivator which stimulates the
      transcriptional activity of the liganded-estrogen receptor (ER). It has been
      reported that AIBI gene is amplified and overexpressed in some breast cancer cell
      lines. AIB1 contains a stretch of homopolymeric glutamines (poly-Q). We reported
      that the poly-Q shows polymorphism, which provides an opportunity to study
      somatic gene alteration such as loss of heterozygosity (LOH). In the present
      study, we aimed to investigate the frequency of somatic gene alteration in
      Japanese patients with breast cancer. Amplification of AIB1 gene was detected
      only in 1 (2.6%) of 39 breast cancer tissues by DNA dot blot analysis. On the
      other hand, LOH was found in 2 (8%) breast cancer tissues out of 25 patients
      showing heterozygosity in peripheral blood mononuclear cells (PBMC). Taken
      together, both LOH and amplification of AIB1 gene were identified in breast
      cancer patients, raising the possibility that AIB1 have oncogenic as well as
      antioncogenic potential for the pathogenesis of breast cancer.

PMID- 11456269
TI  - Detection and identification of subcutaneous adipose tissue protein related to
      obesity in New Zealand obese mouse.
AB  - New Zealand obese (NZO) mouse, a genetic model of obesity, shows hyperphagia,
      hyperinsulinemia and leptin resistance. We analyzed subcutaneous adipose tissue
      proteins in NZO mice with a two-dimensional gel electrophoresis technique
      followed by protein sequence analysis. NZO mice showed hyperinsulinemia and
      hyperleptinemia. Abdominal subcutaneous adipose tissue was inspected in NZO and
      C57BL/6J lean mice. Two-dimensional gel electrophoresis detected 4 spots which
      were obviously reduced in NZO mice. Those spots were p26, p19, p18 and p15.
      Internal sequences of the p26 and p15 protein were homologous with those of
      carbonic anhydrase III, p19 was cytochrome b5, p18 was superoxide dismutase.
      Serum arachidonic acid level in NZO mice was lower by 80% of C57BL/6J mice. The
      present study demonstrated the reduction of several enzymes related to lipid
      metabolism in NZO mice. These data raises the hypothesis that the supposed
      changes of membrane fluidity caused by altered membrane lipid content may involve
      central leptin resistance of this model of obesity.

PMID- 11456270
TI  - Ultrasonographic features of parathyroid carcinoma.
AB  - Although several authors have reported single cases illustrative of some
      ultrasonographic characteristic of parathyroid carcinoma, the value of
      ultrasonography for diagnosing this entity remains to be determined. The purpose
      of our study was to investigate the ultrasonographic features of parathyroid
      carcinoma in a large number of cases. We assessed the shape, contour,
      echogenicity, and depth-width (DW) ratio of 16 parathyroid carcinomas and 61
      parathyroid adenomas. Ultrasonography showed that parathyroid carcinomas tend to
      be large, inhomogeneous, hypoechoic masses with lobulated contours. In contrast,
      parathyroid adenomas were small, homogeneous, hypoechoic masses with smooth
      borders. The mean (range) DW ratios for parathyroid carcinomas were 1.21 (0.91
      2.5) and 0.64 (0.33-1.47) for adenomas; the difference was statistically
      significant (p<0.0001). The DW ratio was > or =1 in 15 (94%) of the 16 cases of
      carcinoma, whereas only 3 (5%) of the 61 adenomas had a similar ratio.
      Ultrasonographic examination is useful not only for preoperative localization but
      also for differentiating parathyroid carcinoma from adenoma. Parathyroid tumors
      with irregular margins, inhomogeneous echogenicity, and a DW ratio > or =1 are
      likely to be malignant.

PMID- 11456271
TI  - PTHrP and PTH/PTHrP receptor expressions in human endometrium.
AB  - We investigated menstrual cycle-dependent changes in the expression of PTHrP and
      PTH/PTHrP receptor in the human endometrium by immunohistochemistry, and
      competitive reverse transcription and polymerase chain reaction (RT-PCR). Human
      endometrial tissues were obtained from patients who underwent gynecological
      surgery due to cervical cancer (carcinoma in situ) or ovarian cancer. The mean
      age of the 20 patients was 36.5 (range 31-44) years. For analysis of mRNA
      expression, specimens from proliferative (mid, n=5; late, n=5) and secretory
      (early, n=4; mid, n=4) phases were used. Immunohistochemical expression of PTHrP
      and PTH/PTHrP receptor was observed in the cytoplasm of both epithelial and
      stromal cells. Stronger staining of PTHrP was found in glandular epithelial cells
      than in stromal cells. The staining during the proliferative phase was stronger
      than that in the secretory phase and the difference was particularly remarkable
      when comparing samples from the same patient. PTH/PTHrP receptor was also present
      in both epithelial and stromal cells of the endometrium. However, no difference
      was observed in receptor expression between the proliferative and secretory
      phases. Competitive RT-PCR revealed that the expression of PTHrP mRNA was higher
      during the proliferative phase than in the secretory phase, although no
      difference was observed in PTH/PTHrP receptor mRNA expression. The data suggest
      that endometrial proliferation may be mediated by a local PTHrP autocrine and/or
      paracrine mechanism.

PMID- 11456272
TI  - Malignant hyperthermia in a patient with Graves' disease during subtotal
      thyroidectomy.
AB  - We report the case of a 31-year-old man with Graves' disease who manifested
      malignant hyperthermia during subtotal thyroidectomy. His past medical history
      and family history were unremarkable. Before surgery, his condition was well
      controlled with propylthiouracil, beta-adrenergic blocker and iodine. During the
      operation, anesthesia was induced by intravenous injection of vecuronium and
      thiopental, followed by suxamethonium for endotracheal intubation. Anesthesia was
      maintained with nitrous oxide and sevoflurane. One hour after induction of
      anesthesia, his end tidal carbon dioxide concentration (ET(CO2)) increased from
      40 to 50 mmHg, heart rate increased from 90 to 100 beats per min and body
      temperature began to rise at a rate of 0.3 degrees C per 15 min. Suspecting
      thyroid storm, propranolol 0.4 mg and methylprednisolone 1,500 mg were
      administered, which, however, had little effect. Despite the lack of muscular
      rigidity, the diagnosis of malignant hyperthermia was made based on respiratory
      acidosis. Sevoflurane was discontinued and dantrolene was given by intravenous
      bolus. Soon after the treatment, ET(CO2), heart rate and body temperature started
      to fall to normal levels. His laboratory findings showed abnormally elevated
      serum creatine phosphokinase and myoglobin but normal thyroid hormone levels.
      Since dantrolene is efficacious in thyrotoxic crisis and malignant hyperthermia,
      an immediate intravenous administration of dantrolene should be considered when a
      hypermetabolic state occurs during anesthesia in surgical treatment for a patient
      with Graves' disease.

PMID- 11456273
TI  - Chronic hypernatremia derived from hypothalamic dysfunction: impaired secretion
      of arginine vasopressin and enhanced renal water handling.
AB  - We analyzed the disorder of water metabolism in a 32 year-old female with chronic
      hypernatremia. She had meningitis at 4 years, and ventriculo-peritoneal shunt
      operation at 13 years because of normal pressure hydrocephalus. At 14 years
      hypernatremia of 166 mmol/l was initially found and thereafter hypernatremia
      ranging from 150 to 166 mmol/l has been persisted for the last 18 years. Physical
      and laboratory findings did not show dehydration. Urine volume was 750-1700 ml
      per day and urinary osmolality (Uosm) 446-984 mmol/kg, suggesting no urinary
      concentrating defect. Plasma arginine vasopressin (AVP) levels ranged from 0.4 to
      1.2 pmol/l despite hyperosmolality of 298 through 343 mmol/kg under ad libitum
      water drinking. There was no correlation between plasma osmolality (Posm) and
      plasma AVP levels, but Uosm had a positive correlation with Posm (r=0.545, P <
      0.05). Hypertonic saline (500 NaCl) infusion after a water load increased Uosm
      from 377 to 679 mmol/kg, and plasma AVP from 0.2 to 1.3 pmol/l. There was a
      positive correlation between Posm and plasma AVP levels in the hypertonic saline
      test (r=0.612, P<0.05). In contrast, an acute water load (20 ml/kg BW) verified
      the presence of impaired water excretion, as the percent excretion of the water
      load was only 8.5% and the minimal Uosm was as high as 710 mmol/kg. Urinary
      excretion of aquaporin-2 remained low in concert with plasma AVP levels. No
      abnormality in pituitary-adrenocortical function was found. These results
      indicate that marked hypernatremia is derived from partial central diabetes
      insipidus and elevated threshold of thirst, and that enhanced renal water
      handling may contribute to maintenance of body water in the present subject.

PMID- 11456274
TI  - Sequence analysis of candidate genes for common susceptibility to type 1 and type
      2 diabetes in mice.
AB  - Although type 1 and type 2 diabetes are regarded as clinically distinct diseases,
      several lines of evidence have suggested common genetic factors between the two
      types of diabetes. The non-obese diabetic (NOD) mouse, an animal model of type 1
      diabetes, and the Nagoya-Shibata-Yasuda (NSY) mouse, a model of type 2 diabetes,
      are derived from the same outbred colony, Jcl:HCR, suggesting a shared
      susceptibility between the two types of diabetes in mice. Genetic as well as
      functional studies have supported the possibility that Tcf2, which encodes the
      transcription factor, hepatocyte nuclear factor 1beta (HNF-1beta), is a candidate
      gene for the common susceptibility between NSY and NOD mice. Txn, encoding
      thioredoxin which is a redox (reduction/oxidation)-active protein, is also a
      positional and functional candidate for a common susceptibility gene. To
      investigate whether either of these two genes is a common susceptibility gene,
      the coding nucleotide sequences of these two genes were compared among the NSY,
      NOD and control C3H strains. The coding sequence of Tcf2 of the NOD mouse was
      identical to that of the C3H mouse, but was different from that of the NSY mouse.
      The coding sequence of Txn was identical in the three strains. These data suggest
      that neither of the two genes is a common susceptiblity gene between type 1 and
      type 2 diabetes in mice.

PMID- 11456275
TI  - TNF-alpha inhibits 3T3-L1 adipocyte differentiation without downregulating the
      expression of C/EBPbeta and delta.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been reported to inhibit adipocyte
      differentiation in which multiple transcription factors including CCAAT enhancer
      binding proteins (C/EBPs) and peroxisome proliferator-activated receptor (PPAR)
      gamma play an important role. Induction of C/EBPalpha and PPARgamma, which
      regulate the expression of many adipocyte-related genes, is dependent on the
      expression of C/EBPbeta and C/EBPdelta at the early phase of adipocyte
      differentiation. To elucidate the mechanism by which TNF-alpha inhibits adipocyte
      differentiation, we examined the effect of TNF-alpha on the expression of these
      transcription factors in mouse 3T3-L1 preadipocytes. TNF-alpha did not abrogate
      the induction of C/EBPbeta and C/EBPdelta in response to differentiation stimuli.
      In fully differentiated adipocytes, TNF-alpha rapidly induced C/EBPbeta and
      C/EBPdelta, whereas it downregulated the expression of C/EBPalpha and PPARgamma.
      Our results suggest that TNF-alpha inhibits adipocyte differentiation
      independently of the downregulation of C/EBPbeta and C/EBPdelta.

PMID- 11456276
TI  - Coexistence of Graves' disease and struma ovarii: case report and literature
      review.
AB  - We report a rare case of Graves' disease associated with struma ovarii. A 26-year
      old Japanese woman had preexisting Graves' disease and was positive for TSH
      receptor antibody. She had been on antithyroid medication at presentation. She
      noted a mass in the lower left abdomen, which was diagnosed as a left struma
      ovarii by radiological work-up including computed tomography, magnetic resonance
      imaging and scintigraphy. The surgically excised teratomatous tumor, containing
      cystic spaces with thyroid tissue, was histologically proved to be struma ovarii.
      Since thyroid function tests and TSH receptor antibody did not change after
      surgery, her hyperthyroidism was considered to be due to Graves' disease. Our
      case was diagnosed as struma ovarii before surgery using various imaging studies.

PMID- 11456277
TI  - A patient with type 1 diabetes mellitus and cerebellar ataxia associated with
      high titer of circulating anti-glutamic acid decarboxylase antibodies.
AB  - A 66-year-old Japanese woman presenting with recent onset of type 1 diabetes
      mellitus and cerebellar ataxia was admitted to our hospital. Physical examination
      on admission revealed coordinate disturbance due to cerebellar ataxia, and the
      laboratory examination showed marked hyperglycemia with ketosis and impaired
      insulin secretion. Anti-glutamic acid decarboxylase (GAD) antibodies in high
      titer were detected in patient's serum. Immunoblotting showed the patient's serum
      reacted with a 65 kDa protein in tissue extracts from rat pancreas and
      cerebellum, and immunohistochemical study produced positive immunostaining in the
      pancreatic islets of Langerhans, the axons of Purkinje cells and the nerve
      terminals in the granular layers of cerebellum of the rat. This is the first case
      presenting with concomitant type 1 diabetes and cerebellar ataxi associated with
      high titers of circulating anti-GAD antibodies which may play a critical role in
      the development of the diseases.

PMID- 11456278
TI  - Chlamydia pneumonia seropositivity correlates with serum fibrinogen and
      lipoprotein a levels: any role in atherosclerosis?
AB  - The aim of the study is to determine the impact of Chlamydial seropositivity on
      atherosclerosis in a group of patient requiring coronary and/or carotid
      revascularization. A population of 30 diabetic patients (group 3) and 26
      nondiabetic patients (group 2) with angiographically documented coronary and/or
      carotid artery disease were enrolled for the study. Volunteers from the relatives
      of hospital staff with no known disease (n=29; group 1) were included as the
      control group. Serum samples from the participants were assayed for
      cardiovascular risk factors including total serum cholesterol, triglyceride and
      lipoprotein levels, fibrinogen, Hb A1c levels and IgG titers for Chlamydia
      pneumonia (C. pneumonia). Chlamydial seropositivity was analysed further to
      determine a possible impact on atherogenesis. Serum LDL cholesterol levels
      revealed statistically significant difference between groups 1 and 2 (p=0.001).
      There was no difference between groups 2 and 3 regarding LDL cholesterol levels.
      There was no significant difference among the groups with respect to C. pneumonia
      seropositivity and the other atherosclerotic risk factors. Chlamydial
      seropositivity was found to be more frequent in males than in females (p=0.008).
      In the C. pneumonia seropositive group, serum fibrinogen and lipoprotein a levels
      were found to be significantly higher than the seronegative group (p=0.0001 and
      p=0.001, respectively). Other atherogenic risk factors were similar in the
      seropositive and negative groups. The causal role of Chlamydial infections in
      atherosclerotic plaque formation might be due to their influence on the serum
      fibrinogen and lipoprotein a levels.

PMID- 11456279
TI  - Leptin inhibits steroid biosynthesis by human granulosa-lutein cells.
AB  - Absence of leptin secretion compromises reproductive function and fertility in
      the ob/ob mouse which, when given leptin, shows a rise in serum LH levels and
      becomes fertile. Recently, the long and active isoform of the leptin receptor was
      detected in the ovary, indicating that leptin may also show direct gonad-related
      activity. To examine this, we studied the effect of graded doses of human leptin
      on estradiol (E2) and progesterone (P4) concentrations in the culture media of
      human granulosa-lutein cells obtained from follicular fluid of women undergoing
      in vitro fertilization. We also evaluated the mRNA expression of steroidogenic
      acute regulatory protein (StAR), aromatase, and cytochrome P450 17alpha (CYP17)
      in these cells at baseline and after exposure to leptin. Estradiol levels were
      significantly decreased in the media 24 hours after incubation of the cells with
      increasing hLeptin concentrations (10(-11) - 10(-7) mol/l). The maximal 30%
      decrease in E2 production was caused by the 10(-9) mol/l hLeptin concentration;
      however, P4 levels in the media were not influenced by leptin. Exposure of
      granulosa-lutein cells to 10(-9) mol/l hLeptin did not produce any measurable
      changes on StAR, aromatase, or CYP17 mRNA expression. When hLeptin (10(-9) mol/l)
      was co-incubated with increasing concentrations of hCG (1.25 - 10 mlU/ml), IGF-II
      (15-60 ng/ml) or 1-6 desaminated IGF-II (deslGF-II; 15-60 ng/ml), it did not
      modify the elevation of E2 concentrations caused by each of the different
      stimuli. We conclude that leptin suppresses E2 secretion by human granulosa
      lutein cells but does not impair the stimulatory effects of hCG and IGFs on these
      cells. Leptin may play a minor, but direct regulatory role on unstimulated human
      ovarian steroidogenesis by interfering with either the translational or post
      translational steps of the baseline CYP17 and/or aromatase synthesis and/or the
      activation of the enzymes.

PMID- 11456280
TI  - Regulation of hepatic glucose metabolism by translocation of glucokinase between
      the nucleus and the cytoplasm in hepatocytes.
AB  - We studied the role of glucokinase translocation between the nucleus and the
      cytoplasm in hepatocytes. In cultured hepatocytes, both the translocation of
      glucokinase from the nucleus to the cytoplasm and the rate of glucose
      phosphorylation were increased when cells were incubated with high concentrations
      of glucose. The addition of low concentrations of fructose, which is known to
      stimulate glucose phosphorylation, stimulated both glucokinase translocation and
      glucose phosphorylation. There was a good correlation between the increase in
      cytoplasmic glucokinase induced by fructose and that in the glucose
      phosphorylation rate induced by fructose. Furthermore, we observed a linear
      relationship between cytoplasmic glucokinase activity and rate of glucose
      phosphorylation over various glucose concentrations in the absence or presence of
      fructose. These results indicate that glucose phosphorylation in hepatocytes
      depended on glucokinase in the cytoplasmic compartment--that is, the increase in
      the rate of glucose phosphorylation was due to the increase in translocation of
      glucokinase out of the nucleus. Also, oral administration of glucose, fructose,
      or glucose plus fructose to 24-h fasted rats induced translocation of glucokinase
      in the liver. All of these results indicate that hepatic glucose metabolism is
      regulated by the translocation of glucokinase.

PMID- 11456281
TI  - Effect of serotonin depletion by p-chlorophenylalanine on serum prolactin levels
      in estrogen-treated ovariectomized rats: insights concerning the serotoninergic,
      dopaminergic and opioid systems.
AB  - The stimulatory effect of serotonin on prolactin secretion is well documented,
      and the administration of an inhibitor of serotonin synthesis (p
      chlorophenylalanine - pCPA) has the expected inhibitory action on prolactin
      release in most experimental situations. However, there is evidence that in
      certain physiological or experimental conditions, activation of the
      serotoninergic system can also determine inhibition of prolactin secretion. The
      aim of the present study was to investigate the ability of estrogen to modify the
      effect of pCPA on prolactin secretion and to evaluate the participation of opioid
      and/or dopaminergic systems in regulating pCPA-induced prolactin secretion in
      estradiol-treated rats. We observed that pCPA administration (200 mg/kg/day,
      s.c., 2 days) to ovariectomized (OVX) female rats treated with estradiol benzoate
      (300 microg/week for 2 weeks, or 50 microg/week for 4 weeks, s.c.) causes a
      significant increase in serum prolactin, whereas no effect is observed in intact
      rats or in OVX rats without treatment. Bromocriptine administration completely
      reversed prolactin values previously increased by estradiol and by pCPA [OVX rats
      + estradiol = 86.50 ng/ml (68.90-175.02), OVX + estradiol + pCPA = 211.30 ng/ml
      (142.03-311.00), OVX + estradiol + pCPA + bromocriptine = 29.35 ng/ml (23.01 -
      48.74), p<0.05. Naloxone administration partially reduced estrogen-induced high
      prolactin concentrations, but did not affect prolactin secretion stimulation
      determined by pCPA. Overall, the data from this report confirm the involvement of
      the dopaminergic system and, to a lesser degree, of endogenous opioids in
      prolactin secretion stimulation determined by estradiol. Furthermore, our results
      suggest that the stimulatory action of pCPA on prolactin secretion in estradiol
      treated OVX rats is mediated by serotonin, which may also act indirectly on
      dopamine neurons.

PMID- 11456282
TI  - Mitochondrial respiration and triiodothyronine concentration in liver from
      postpubertal and adult rats.
AB  - The purpose of this study was to investigate the decline in rat liver
      mitochondria respiration found in adult rats compared to younger ones, and to
      find a link between this respiratory impairment and a tissue hypothyroidism
      state. To this end, hepatic concentration and serum levels of triiodothyronine
      were measured in postpubertal rats (60 days old) and adult rats (180 days old).
      In addition, in these rats we measured oxidative phosphorylation in homogenate
      together with coupled and uncoupled respiration in isolated mitochondria using
      succinate or durohydroquinone as substrate. We found that mitochondria from adult
      rats consumed less oxygen compared to younger rats due to lower electron
      transport chain and phosphorylating system activity. In addition, we found that
      in state 4 condition, mitochondria from adult rats consumed less oxygen than
      mitochondria from young rats. Finally, we found a decrease in liver
      triiodothyronine concentration in adult rats. In conclusion, the results of this
      study show that hepatic mitochondria in adult rats have a decreased ATP synthesis
      capacity and proton permeability, both consistent with the tissue hypothyroidism
      found in the liver of adult rats.

PMID- 11456283
TI  - Luteal phase of the menstrual cycle in young healthy women is associated with
      decline in interleukin 2 levels.
AB  - The aim of this study was to look at the possible changes in the blood levels of
      Interleukin 2 (IL2) during the sexual cycle in generally healthy, young,
      regularly menstruating women. The concentrations of progesterone and 17beta
      estradiol were measured using radioimmunological assay. The bioactivity of
      interleukin 2 was measured using a biological test on the IL2-sensitive CTLL cell
      line. The percentage of lymphocytes with intracellular IL2 was determined by flow
      cytometry. Eighteen healthy volunteers (19-29 years old) were examined on days 5,
      8, 14, 18 and 25 of the same cycle. All women were characterised by a regular
      menstrual cycle as per physiological levels of 17beta-es-tradiol and
      progesterone. The luteal phase of the cycle was characterised by both a decrease
      of IL2 blood levels and a decrease in the percentage of intracellular 1L2
      containing lymphocytes stimulated in vitro. The IL2 level fluctuations observed
      during the menstrual cycle may be one factor causing pre-menstrual infections
      observed in young women. On the other hand, the decrease of IL2 may be seen as a
      start of the immune suppression necessary for an embryo's nidation.

PMID- 11456284
TI  - Clinical, biochemical and molecular genetic data in five children with Gitelman's
      syndrome.
AB  - Gitelman's variant of Bartter's syndrome, inherited hypokalemic alkalosis, is
      caused by mutation in the thiazide-sensitive NaCl co-transporter (NCCT). The main
      clinical symptoms are: muscular weakness, carpopedal spasm, constipation and
      short stature. The diagnosis was suspected in five children according to clinical
      criteria. All patients exhibited carpopedal spasm during febrile illness, three
      patients had short stature. Biochemical features were: metabolic alkalosis,
      hypokalemia, hypomagnesemia, low IGF-I levels, hyperkaliuria, hypernatriuria,
      hypocalciuria and normoprostaglandinuria. Three patients had elevated plasma
      renin activity and hyperaldosteronism. Mutational analysis of the NCCT gene
      confirmed the diagnosis in all five patients. Different forms of therapy,
      potassium and magnesium substitution, spironolactone and indomethacin failed to
      fully correct hypokalemia and hypomagnesemia, but markedly improved growth
      velocity and normalized IGF-I levels in the three patients with short stature.
      During therapy, clinical symptoms disappeared. We conclude that Gitelman's
      syndrome is a disorder with a variable symptom profile, but can be suspected on
      clinical signs already in early childhood. The early diagnosis is essential in
      preventing complications.

PMID- 11456285
TI  - Effect of glycine on insulin secretion and action in healthy first-degree
      relatives of type 2 diabetes mellitus patients.
AB  - The aim of this study was to identify the effect of glycine on insulin secretion
      and action in healthy first-degree relatives of Type 2 diabetes mellitus
      patients. A randomized, double-blind, placebo-controlled clinical trial was
      performed in 12 healthy, non-obese volunteers who were first-degree relatives of
      Type 2 diabetes mellitus patients. Six volunteers received a morning dose of
      glycine 5 g orally and the other six received placebo. At baseline without drugs
      and after pharmacological intervention, a metabolic profile and, to assess
      insulin secretion and action, a hyperglycemic-hyperinsulinemic clamp study were
      performed. There were no significant differences in baseline metabolic profile,
      insulin secretion or action between groups. Changes from baseline of early (p <
      0.05), late (p < 0.05), and total insulin (p < 0.02) responses were higher in the
      glycine group than in controls. There were no significant differences in the
      changes from baseline of insulin action between groups. In conclusion, a morning
      dose of glycine 5 g orally increased early, late and total insulin responses
      without changes in insulin action in healthy first-degree relatives of Type 2
      diabetes mellitus patients.

PMID- 11456286
TI  - Gliclazide mainly affects insulin secretion in second phase of type 2 diabetes
      mellitus.
AB  - We studied the effect of the acute administration of gliclazide at 160 mg on
      insulin release during hyperglycaemic clamps in 12 type 2 diabetes patients, age
      50 +/- 9.0 years, diabetes duration 5.5 +/- 4.8 years, fasting blood glucose 9.6
      +/- 2.1 mmol/L (means +/- SD). After a 210 min of hyperinsulinaemic euglycaemic
      clamp (blood glucose 4.6 +/- 0.14mmol/L), gliclazide or placebo (randomised,
      double-blind, cross-over) was administered; 60 minutes later, a hyperglycaemic
      clamp (4hr) at 8mmol/L was started. Plasma C-peptide levels increased
      significantly after the administration of gliclazide (increment 0.17 +/- 0.15 vs.
      0.04 +/- 0.07 nmol/L, p = 0.024) before the clamp. After the start of the
      hyperglycaemic clamp, the areas under the curve (AUC) for insulin and C-peptide
      did not differ from 0-10 min (first phase) with gliclazide. However, second-phase
      insulin release (30-240 min) was markedly enhanced by gliclazide. AUC plasma
      insulin (30 to 240 min) was statistically significantly higher after gliclazide
      (12.3 +/- 13.9 vs. -0.56 +/- 9.4 nmol/L x 210 min, p = 0.022); similarly, AUC
      plasma C-peptide (30 to 240 min) was also higher: 128 +/- 62 vs. 63 +/- 50 nmol/L
      x 210 min, p = 0.002). In conclusion, in long-standing type 2 diabetes the acute
      administration of gliclazide significantly enhances second phase insulin release
      at a moderately elevated blood glucose level. In contrast to previous findings in
      mildly diabetic subjects, these 12 type 2 diabetes patients who had an
      inconsiderable first phase insulin release on the placebo day, only showed an
      insignificant increase in first phase with gliclazide.

PMID- 11456287
TI  - Effects of troglitazone and voluntary running on insulin resistance induced high
      fat diet in the rat.
AB  - It is well known that troglitazone and voluntary running have the capacity to
      improve insulin resistance. The purpose of this study was to evaluate the
      combination effect of troglitazone and voluntary running on insulin action.
      Female rats aged 7 weeks were divided into high-fat diet (HF), high-fat diet +
      troglitazone (0.3% in diet; Tg), high-fat diet + voluntary running (for 3 wks;
      Tr), high-fat diet + troglitazone + voluntary running (Tg-Tr), and control (C)
      groups. A sequential euglycemic clamp experiment with two different insulin
      infusion rates of 3.0 (L-clamp) and 30.0 mU/kg BW/min (H-clamp) was performed on
      these rats after an overnight fast. Blood glucose concentrations were kept at
      fasting levels by periodic adjustment of the intravenous glucose infusion rate
      during the clamp experiment. Glucose infusion rates (GIRs) calculated from 60 to
      90, 150 to 180 min were regarded as an index of whole body insulin action. After
      the clamp experiment, we determined the amount of glycogen content in the
      gastrocnemius muscle. Fat feeding markedly reduced GIRs in both L- and H- clamp
      experiments compared with C. Troglitazone treatment did not improve high-fat
      induced insulin resistance. In both L- and H-clamp experiments, GIRs were
      increased by voluntary running compared with HF, and reached the same levels as
      in C. GIRs of Tg-Tr were not greater than those of Tr. Glycogen content in
      gastrocnemius muscle showed the same trend as the results for GIRs. Therefore,
      the combination effect of troglitazone and voluntary running on insulin action
      was not found, but the effect of voluntary running was shown in fat-induced
      insulin resistance.

PMID- 11456288
TI  - Glycemic control reverses increases in urinary excretions of immunoglobulin G and
      ceruloplasmin in type 2 diabetic patients with normoalbuminuria.
AB  - To examine whether urinary excretions of plasma proteins with molecular radii of
      45-55 A and different isoelectric points such as IgG (pI = 7.4) and ceruloplasmin
      (pI = 4.4) increase selectively in normoalbuminuric type 2 diabetic patients,
      urinary albumin excretion rate (AER), renal clearances of IgG, ceruloplasmin and
      alpha2-macroglobulin, and creatinine clearance (Ccr) were studied in timed
      overnight urine samples of 36 diabetic outpatients and 16 control subjects.
      Furthermore, to examine effect of glycemic control on these urinary protein
      excretions, the same analysis was performed before and after glycemic control in
      17 diabetic inpatients admitted for glycemic control. Renal clearances of IgG and
      ceruloplasmin were significantly higher in diabetic outpatients than in the
      control group, whereas AER and renal clearance of alpha2-macroglobulin did not
      differ. Glycemic control caused significant decreases in renal clearances of IgG
      and ceruloplasmin, accompanied with tendency for Ccr to decrease (p = 0.055). The
      present results, together with our previous finding of selectively increased
      urinary excretions of 45-55 A sized plasma proteins in parallel with enhanced
      glomerular filtration rate after acute protein loading, led us to conclude that
      enhanced intraglomerular hydraulic pressure may cause increases in clearances of
      IgG and ceruloplasmin, and that this change can be reversed by strict glycemic
      control in normoalbuminuric diabetic patients.

PMID- 11456289
TI  - Inhibition of insulin release by urotensin II--a study on the perfused rat
      pancreas.

PMID- 11456290
TI  - Laboratory method for high-solids countercurrent fermentations.
AB  - Equipment and procedures were developed to study the conversion of
      lignocellulosic biomass to carboxylic acids using high-solids countercurrent
      fermentations. Countercurrent fermentations of cattle manure yielded a rapid
      fermentation (maximum 2.98 g of total acid/[L x d]) with high acid concentrations
      (maximum of 32.5 g of total acid/L), but the acid yield tended to be low (maximum
      of 0.24 g of total acid/g of volatile solids). Countercurrent fermentations of a
      mixture of 80% municipal solid waste/20% sewage sludge fermented more slowly
      (maximum of 1.98 g of total acid/[L x d]) with a lower acid concentration
      (maximum of 26.5 g of total acids/L), but higher acid yields were achieved
      (maximum of 0.34 g of total acid/g of volatile solids).

PMID- 11456291
TI  - Single-Step purification and immobilization of penicillin acylase using
      hydrophobic ligands.
AB  - Five different hydrophobic ligands immobilized on 4% (4XL) and 6% (6XL)
      crosslinked agarose were used to study the single-step purification of penicillin
      acylase from cell lysate. The 4XL gels showed relatively higher specific activity
      and recovery than the 6XL gels. In single-step purification, highly active enzyme
      (42 U/mg) was obtained using moderately hydrophobic ligand (octyl). The crude
      enzyme immobilized on octyl gel by adsorption showed significant operational
      stability over a period of 30 d at room temperature. Reactor studies demonstrated
      the feasibility of hydrophobic ligands as a medium for immobilization.

PMID- 11456292
TI  - Fiber fractions from processing of barley in production and conservation of a
      biologic control agent.
AB  - Carriers are frequently used to overcome problems associated with microbial
      survival in soil after inoculation. Moreover, the use of carriers can prolong the
      shelf lives and lessen dusting of both biofungicides and biologic fertilizers.
      This study investigated the suitability of barley-based fiber fractions as growth
      media and immobilization matrices in the cultivation of a Streptomyces
      griseoviridis biologic control agent, as well as for the conservation of obtained
      biomass in dehydrated hydrogel capsules. The second main ingredient in all the
      examined carrier matrices was alginate. The aim was to find a hydrogel
      formulation suited for a production process in which all individual steps,
      including cultivation of the organism; downstream processing; and formulation,
      storage, and application of the product (i.e., biologic control agent), are
      carried out in the hydrogel matrix. Of the tested fractions, brewer's spent grain
      was the best choice, when considering the price vs the nutrient contents as well
      as the storage time and ease of processing of the crude and the finished
      products. It seems that cereal fibers can be replenished with cereal fractions
      less rich in fiber but having a higher content of utilizable nutrients and,
      hence, better suited for the production of biomass. A high content of water
      insoluble fiber favorably influenced the appearance as well as the applicability
      of the products.

PMID- 11456293
TI  - Modeling of saccharide utilization in primary beer fermentation with yeasts
      immobilized in calcium alginate.
AB  - Immobilized beer fermentation was studied using an industrial bottom-fermenting
      yeast strain Saccharomyces cerevisiae. The yeast cells were immobilized in 2.5%
      calcium alginate gel and used for brewing in a five-vessel cascade reactor. The
      fermentation was performed at 15 degrees C at various flow rates. A nonstructured
      mathematical model was developed to simulate the performance of continuous
      primary fermentation of lager beer. The model was based on the following
      variables: maltose, maltotriose, glucose, fructose, ethanol, and cell
      concentration. Experimental values of these variables were determined in samples
      taken at regular intervals. For experimental data fitting a nonlinear regression
      was used. Substrate consumption was characterized by specific substrate
      consumption rate and saturation constant. The values of these two parameters were
      optimized for all four substrates. Inhibition effects of substrates and product
      were analyzed using various inhibition patterns. Only the inhibition effect of
      maltose on maltose consumption was clearly identified. A good-fitting
      relationship for maltose inhibition was found, and inhibition constants were
      calculated.

PMID- 11456294
TI  - Application of factorial design to the study of xylitol production from
      eucalyptus hemicellulosic hydrolysate.
AB  - This study deals with the bioconversion of xylose into xylitol by Candida
      guilliermondii FTI 20037 using eucalyptus hemicellulosic hydrolysate obtained by
      acid hydrolysis. The influence of various parameters (ammonium sulfate, rice
      bran, pH, and xylose concentration) on the production of xylitol was evaluated.
      The experiments were based on multivariate statistical concepts, with the
      application of factorial design techniques to identify the most important
      variables in the process. The levels of these variables were quantified by the
      response surface methodology, which permitted the establishment of a significant
      mathematical model with a coefficient determination of R2 = 0.92. The best
      results (xylitol = 10.0 g/L, yield factor = 0.2 g/g, and productivity = 0.1 g/[L
      x h]) were attained with hydrolysate containing ammonium sulfate (1.1 g/L), rice
      bran (5.0 g/L), and xylose (initial concentration of 60.0 g/L), after 72 h of
      fermentation. The pH of fermentation was adjusted to 8.0 and the inoculum level
      utilized was 3 g/L.

PMID- 11456295
TI  - Production of poly(3-hydroxybutyrateco-3-hydroxyvalerate) from cottonseed oil and
      valeric acid in batch culture of Raistonia sp. strain JC-64.
AB  - A Ralstonia sp. strain JC-64 that is capable of accumulating poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) (P[3HB-co-3HV]) from cottonseed oil and
      valeric acid was isolated. By using a high limiting-nitrogen (HLN) mineral medium
      as the medium for the second stage of the fermentation process and by adding the
      two carbon sources at different times, a range of copolymers with 12-62 mol% of
      3HV were produced from a series of HLN mineral mediums containing different
      compositions of cottonseed oil and valeric acid by Ralstonia sp. JC-64. The
      melting temperature (Tm) of polyhydroxybutyrate from cottonseed oil was 174
      degrees C and that of P(3HB-co-3HV) with the highest 3HV-mol fraction (62%) was
      81 degrees C.

PMID- 11456296
TI  - Application of near-infrared spectra on temperature-controlled protein
      crystallization: a simulation study.
AB  - Large, high-quality protein crystals are required for the structural
      determination of proteins via X-ray diffraction. In this article, we propose a
      technique to facilitate the production of such crystals and validate its
      feasibility through simulations. An analytical method for protein aqueous
      solution based on a Fourier transform infrared (FTIR) spectroscopy is combined
      with a temperature control strategy to manipulate the extent of supersaturation
      during crystal growth, thus impacting crystal quality. The technique requires
      minimal knowledge about the growth kinetics a priori. The simulations show that,
      under ideal conditions, the design can be as effective as predesigned temperature
      programs for crystallization based on known growth kinetics. Two kinds of errors
      might be encountered with this design. Error in the estimated number of seed
      crystals can result in a growth rate deviating from the desired one.
      Nevertheless, the deviation is usually tolerable and system instability is
      unlikely to occur. Based on the standard error of our FTIR method, errors in
      concentration measurement are simulated. Measurement error can result in system
      instability and impair the control algorithm. Such errors may be compensated by
      limiting the temperature change taken by the control action, or by improving the
      measurement precision through the use of regressed concentrations. Through
      simulations, it is shown that the proposed design is practical and represents a
      significant improvement over the commonly used isothermal crystallization
      technique.

PMID- 11456297
TI  - Proteolysis of mesophilic and thermophilic alpha-amylases: a comparative study.
AB  - A comparative study was performed on limited and extensive proteolysis of
      mesophilic (from Bacillus amyloliquefaciens [BAA]) and thermophilic (from
      Bacillus licheniformis [BLA]) alpha-amylases using trypsin. As expected, the
      thermophilic enzyme showed greater resistance to digestion by the protease. While
      the catalytic potential of BLA was enhanced on proteolysis, that of BAA was
      diminished owing to this process. Combined with greater catalytic activity, a
      lower thermal stability was observed for BLA on proteolytic treatment. For both
      enzymes, the extent of proteolytic cleavage was reduced in the presence of
      various stabilizing agents. The digestion patterns are explained in terms of
      available information in the literature on the structure of these proteins,
      especially in relation to segmental mobility.

PMID- 11456298
TI  - Progressive mitochondrial disease resulting from a novel missense mutation in the
      mitochondrial DNA ND3 gene.
AB  - We describe a 42-year-old man who presented with a progressive history of
      epilepsy, stroke-like episodes, bilateral optic atrophy, and cognitive decline.
      Investigation of his muscle biopsy revealed a specific defect in complex I
      activity. Subsequent analysis of the mitochondrial genome identified a novel
      heteroplasmic T10191C mutation in the ND3 gene. The mutation was present at lower
      levels in blood from the patient and unaffected maternal relatives and is the
      first pathogenic mitochondrial DNA mutation in the ND3 gene to be described.

PMID- 11456299
TI  - Late-onset metachromatic leukodystrophy clinically presenting as isolated
      peripheral neuropathy: compound heterozygosity for the IVS2+1G-->A mutation and a
      newly identified missense mutation (Thr408Ile) in a Spanish family.
AB  - We report the case of a 50-year-old woman and her 32-year-old daughter, both of
      whom are affected with adult-onset metachromatic leukodystrophy (MLD) clinically
      presenting as peripheral neuropathy. Arylsulfatase A (ARSA) activities were
      markedly reduced, and electrophysiology showed a severe demyelinating neuropathy
      with features of chronic acquired demyelinating polyneuropathy. Molecular genetic
      studies of the family revealed that the proband and her affected daughter are
      compound heterozygotes for the common IVS2+ 1G-->A mutation and a newly
      identified missense mutation, Thr408Ile. This case indicates that adult
      metachromatic leukodystrophy should be considered in adult patients with
      demyelinating peripheral neuropathy of unknown etiology.

PMID- 11456300
TI  - Dichloroacetate exerts therapeutic effects in transgenic mouse models of
      Huntington's disease.
AB  - Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity
      and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q transgenic
      mouse models of Huntington's disease (HD), DCA significantly increased survival,
      improved motor function, delayed loss of body weight, attenuated the development
      of striatal neuron atrophy, and prevented diabetes. The percentage of PDHC in the
      active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA
      ameliorated the deficit. These results provide further evidence for a role of
      energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic
      benefits in HD.

PMID- 11456301
TI  - Familial frontotemporal dementia and parkinsonism with a novel mutation at an
      intron 10+11-splice site in the tau gene.
AB  - We report a case of familial frontotemporal dementia and parkinsonism
      characterized by early onset with mental retardation. The patient died at the age
      of 54; neuronal loss was severe in the frontal and temporal cortices, globus
      pallidus, substantia nigra, red nucleus and dentate nucleus. Anti-tau-positive
      fibrillary changes were observed in neurons and glia in these regions. Although
      the patient had 2 novel point mutations of the tau gene, P301P (CCG to CCA) and
      an intron 10+11-splice site (T to C), exon trapping analysis indicated that the
      latter was pathogenic.

PMID- 11456302
TI  - Recommended diagnostic criteria for multiple sclerosis: guidelines from the
      International Panel on the diagnosis of multiple sclerosis.
AB  - The International Panel on MS Diagnosis presents revised diagnostic criteria for
      multiple sclerosis (MS). The focus remains on the objective demonstration of
      dissemination of lesions in both time and space. Magnetic resonance imaging is
      integrated with dinical and other paraclinical diagnostic methods. The revised
      criteria facilitate the diagnosis of MS in patients with a variety of
      presentations, including "monosymptomatic" disease suggestive of MS, disease with
      a typical relapsing-remitting course, and disease with insidious progression,
      without clear attacks and remissions. Previously used terms such as "clinically
      definite" and "probable MS" are no longer recommended. The outcome of a
      diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but
      for whom diagnostic evaluation is equivocal), or "not MS."

PMID- 11456303
TI  - Increased hair polyamine levels in patients with Alzheimer's disease.

PMID- 11456304
TI  - Hiccups start, seizures cease.

PMID- 11456305
TI  - Small fibers involvement in Friedreich's ataxia.
AB  - Although the involvement of large myelinated sensory fibers in Friedreich's
      ataxia (FA) is well documented, an impairment of unmyelinated fibers has not been
      described. We demonstrate an involvement of cutaneous unmyelinated sensory and
      autonomic nerve fibers in FA patients. We performed a morphological and
      functional study of cutaneous nerve fibers in 14 FA patients and in a population
      of control subjects. We used immunohistochemical techniques and confocal
      microscopy applied to punch skin biopsies from thigh, distal leg, and fingertip,
      and compared the density of epidermal nerve fibers (ENFs) with the results of
      mechanical pain sensation and thermal and tactile thresholds performed on hand
      dorsum, thigh, distal leg, and foot dorsum. We observed in our patients a
      statistically significant loss of ENFs, a reduced innervation of sweat glands,
      arrector pilorum muscles and arterioles, and an impairment of thermal and tactile
      thresholds and mechanical pain detection.

PMID- 11456306
TI  - Sodium channel inactivation in an animal model of acute quadriplegic myopathy.
AB  - We previously demonstrated that muscle fibers become unable to fire action
      potentials in both patients and an animal model of acute quadriplegic myopathy
      (AQM). In the animal model, skeletal muscle is denervated in rats treated with
      high-dose corticosteroids (steroid-denervated; SD), and muscle fibers become
      inexcitable despite resting potentials and membrane resistances similar to those
      of control denervated fibers that remain excitable. We show here that
      unexcitability of SD fibers is due to increased inactivation of sodium channels
      at the resting potential of affected fibers. A hyperpolarizing shift in the
      voltage dependence of inactivation in combination with the depolarization of the
      resting potential induced by denervation results in inexcitability. Our findings
      suggest that paralysis in the animal model of AQM is the result of an abnormality
      in the voltage dependence of sodium channel inactivation.

PMID- 11456307
TI  - Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease
      patients' relatives with a decreased sense of smell.
AB  - By the time a clinical diagnosis of Parkinson's disease (PD) is made, a
      significant loss of dopaminergic neurons has already occurred. Identifying
      patients in the period between the presumed onset of dopaminergic cell loss and
      the appearance of clinical parkinsonism may be of major importance in the
      development of effective neuroprotective treatment strategies. In an effort to
      develop a feasible strategy to detect preclinical PD, a combination of olfactory
      processing tasks, including odor detection, odor identification, and odor
      discrimination was used to select groups of hyposmic and normosmic individuals
      from a total of 250 relatives (parents, siblings, or children) of subjects with
      PD. Single photon emission computed tomography (SPECT) with [123I]beta-CIT as a
      dopamine transporter ligand was used to assess nigrostriatal dopaminergic
      function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal
      reduction in striatal dopamine transporter binding was found in 4 out of 25
      hyposmic relatives of PD patients, two of whom subsequently developed clinical
      parkinsonism, and in none of the 23 normosmic relatives. These observations
      demonstrate that subclinical reductions in dopamine transporter binding can be
      detected in asymptomatic relatives of sporadic PD patients by means of [123I]beta
      CIT and SPECT. The results further indicate that olfactory deficits may precede
      clinical motor signs in PD.

PMID- 11456308
TI  - Diagnosis of X-linked myotubular myopathy by detection of myotubularin.
AB  - Mutations in the MTM1 gene cause X-linked recessive myotubular myopathy (XLMTM;
      MIM310400). Myotubularin, the implicated protein, is a phosphoinositide
      phosphatase that belongs to a large protein family conserved through evolution
      that also includes the antiphosphatase Sbfl and the protein hMTMR2 mutated in
      Charcot-Marie-Tooth type 4B. Myotubularin is detectable in a variety of cell
      lines by immunoprecipitation followed by Western blotting. We screened 29
      independant patients with XLMTM phenotype and four with centronuclear myopathy.
      87% (21/24) of patients with known MTM1 mutations showed abnormal myotubularin
      levels, including some with missense mutations. Moreover, myotubularin was also
      undetectable in a patient for whom no mutation could be identified by SSCP
      screening. The centronuclear cases investigated have a normal level of protein,
      suggesting that the centronuclear form is not the result of a decrease in
      myotubularin level. Thus, immunoprecipitation of myotubularin from cultured cells
      represents a rapid and helpful method for classifying those cases where no
      mutation was found. On the other hand, the amount of expression may be of
      diagnostic value for disease course in patients with a mutation.

PMID- 11456309
TI  - PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar
      to those of human CMT1A.
AB  - Charcot-Marie-Tooth 1A (CMT1A) neuropathy is caused by duplication of the
      peripheral myelin protein 22 (PMP22) gene, leading to protein overexpression.
      Although this protein has a role in regulating Schwann cell growth and peripheral
      myelin compaction, how altered concentrations of PMP22 impair myelination is
      unknown. We established dorsal root ganglia (DRG) cultures from a transgenic rat
      overexpressing PMP22 (PMP22tg) to study the behavior of PMP22tg Schwann cells in
      early stages of development and myelination. We used reverse transcriptase
      polymerase chain reaction and light and electron microscopy to study PMP22
      expression and myelin formation. Myelin ultrastructure was evaluated in sural
      nerves from CMT1A patients to compare experimental and human findings. PMP22tg
      DRG cultures contained a greater number of internodes devoid of myelin, in the
      absence of remyelination, and increased periodicity of myelin lamellae compared
      with normal cultures. Widening of myelin lamellae was also observed in CMT1A
      biopsy specimens. Our results suggest that both functions of PMP22, in regulating
      Schwann cell differentiation and contributing to peripheral myelin compaction,
      are affected by its overexpression. The presence of similar myelin abnormalities
      in PMP22tg cultures and human nerves emphasizes the importance of developing in
      vitro models of hereditary neuropathies to study their underlying
      pathomechanisms.

PMID- 11456310
TI  - Prospective study of caffeine consumption and risk of Parkinson's disease in men
      and women.
AB  - Results of case-control studies and of a prospective investigation in men suggest
      that consumption of coffee could protect against the risk of Parkinson's disease,
      but the active constituent is not clear. To address the hypothesis that caffeine
      is protective against Parkinson's disease, we examined the relationship of coffee
      and caffeine consumption to the risk of this disease among participants in two
      ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses'
      Health Study (NHS). The study population comprised 47,351 men and 88,565 women
      who were free of Parkinson's disease, stroke, or cancer at baseline. A
      comprehensive life style and dietary questionnaire was completed by the
      participants at baseline and updated every two to four years. During the follow
      up (10 years in men, 16 years in women), we documented a total of 288 incident
      cases of Parkinson's disease. Among men, after adjustment for age and smoking,
      the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23-0.78; p for trend
      < 0.001) for men in the top one-fifth of caffeine intake compared to those in the
      bottom one-fifth. An inverse association was also observed with consumption of
      coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend <
      0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women,
      the relationship between caffeine or coffee intake and risk of Parkinson's
      disease was U-shaped, with the lowest risk observed at moderate intakes (1-3 cups
      of coffee/day, or the third quintile of caffeine consumption). These results
      support a possible protective effect of moderate doses of caffeine on risk of
      Parkinson's disease.

PMID- 11456311
TI  - Neuroimmunophilins: novel neuroprotective and neuroregenerative targets.
AB  - Cyclosporin A (CsA) and FK506 (tacrolimus) are immunosuppresants that are widely
      used in organ transplantation. CsA is an 11-member cyclic peptide, whereas FK506
      is a macrolide antibiotic. Recently, these powerful and useful compounds have
      become of great interest to neuroscientists for their unique neuroprotective and
      neuroregenerative effects. These drugs and nonimmunosuppressive analogs protect
      neurons from the effects of glutamate excitotoxicity, focal ischemia, and 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell
      death. They also stimulate functional recovery of neurons in a variety of
      neurologic injury paradigms. These drugs exert their effects via immunophilins,
      the protein receptors for these agents. The immunophilin ligands show particular
      promise as a novel class of neuroprotective and neuroregenerative agents that
      have the potential to treat a variety of neurologic disorders.

PMID- 11456312
TI  - Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in
      myasthenia gravis.
AB  - Antibodies to muscle acetylcholine receptors, to other muscle antigens, and to
      some cytokines are found in the majority of patients with thymic tumors
      (thymomas) and myasthenia gravis (MG). The role of the tumor in initiating
      autoimmunity, however, is unclear; in particular, it is not known whether the
      thymoma exports mature and long-lived T cells, which could provide help for
      antibody production in the periphery. Here, we quantified recently exported
      thymic T cells using the approach of measuring episomal DNA fragments [T-cell
      receptor excision circles (TRECs)], generated by T-cell receptor gene
      rearrangement. Compared to values in healthy individuals (n = 10) or in patients
      with late-onset MG (n = 8), TREC levels were significantly raised in both the
      CD4+ and CD8+ peripheral blood compartments of patients with thymoma and MG (n =
      14, p = 0.002 and p = 0.0004 compared to healthy controls) but only in the CD8+
      compartment of the three patients with thymoma without MG (p = 0.4 and p = 0.01
      for CD4+ and CD8+). TREC levels decreased following thymectomy to values similar
      to controls but were substantially raised in patients who had developed tumor
      recurrence (n = 6, p = 0.04 and p = 0.02 for CD4+ and CD8+); this was associated
      with increased antibodies to interferon-alpha and interleukin-12 in the one case
      studied serially. Collectively, these results support the hypothesis that the
      neoplastic thymoma tissue itself can generate and export mature, long-lived T
      cells and that these T cells reflect the thymic pathology and are likely to be
      related to the associated autoimmune diseases. The results also provide a new
      approach for early diagnosis of thymoma recurrence.

PMID- 11456313
TI  - Potassium channel antibodies in two patients with reversible limbic encephalitis.
AB  - Limbic encephalitis (LE) is often associated with lung, thymic, or testicular
      tumours and antibodies to Hu, CV2, or Ma2 (Ta) antigens. In these cases, it
      generally has a poor prognosis. Here we describe two patients with symptoms of
      LE, negative for typical paraneoplastic antibodies, in whom antibodies to voltage
      gated potassium channels (VGKC) were detected retrospectively in serial serum
      samples. Patient 1 had a thymoma recurrence, but in patient 2 no tumour has been
      detected in the years following presentation. Plasma exchange was effective in
      reducing VGKC antibody levels, with substantial improvement in mental symptoms in
      patient 1. In patient 2, the VGKC antibodies fell spontaneously over two years,
      with almost complete recovery of mental function. Although neither patient had
      obvious neuromyotonia at presentation, both showed excessive secretions. We
      suggest that patients with limbic symptoms and excessive secretions should be
      tested for VGKC antibodies, and, if they are present, prompt and effective
      immunosuppressive treatment should be considered.

PMID- 11456314
TI  - Brain magnetic resonance imaging in 23 patients with mucopolysaccharidoses and
      the effect of bone marrow transplantation.
AB  - A longitudinal study of cranial magnetic resonance imaging (MRI) was carried out
      in 23 patients with mucopolysaccharidoses (MPS); 1 each of types IH, VI, and VII;
      2 of type IS; 10 of type II; and 4 each of types IIIB and IVA. Six types of
      distinct abnormalities were 1) cribriform changes or spotty changes in the corpus
      callosum, basal ganglia, and white matter; 2) high-intensity signal in the white
      matter on T2-weighted image; 3) ventriculomegaly; 4) diffuse cerebral cortical
      atrophy; 5) spinal cord compression; and 6) megacisterna magna. The cribriform
      changes that corresponded to dilated perivascular spaces were found in the
      patients with MPS IS, II, and VI. The patchy and diffuse intensity changes were
      found in the patient with MPS II and IIIB, respectively. MPS IH and the severe
      type of MPS II showed marked ventriculomegaly. Marked cerebral atrophy was
      observed in all MPS IIIB patients and in the severe type of MPS II patients.
      Spinal cord compression was a feature usually observed in MPS IH, IVA, VI, and
      VII. Megacisterna magna was frequent in the patients with MPS II (6/10). In two
      of five patients, the therapeutic effect of bone marrow transplantation (BMT) was
      remarkable. Both the cribriform changes and the intensity change of the white
      matter in a MPS VI patient disappeared eight years after the BMT. Slight
      improvement of cribriform change was noted in one patient with MPS II three years
      after the BMT. MRS was not sufficient to estimate the accumulation of
      glycosaminoglycans but was useful for evaluating neuronal damages.

PMID- 11456315
TI  - Microarray analysis of hippocampal gene expression in global cerebral ischemia.
AB  - The brain's response to ischemia, which helps determine clinical outcome after
      stroke, is regulated partly by competing genetic programs that respectively
      promote cell survival and delayed cell death. Many genes involved in this
      response have been identified individually or systematically, providing insights
      into the molecular basis of ischemic injury and potential targets for therapy.
      The development of microarray systems for gene expression profiling permits
      screening of large numbers of genes for possible involvement in biological or
      pathological processes. Therefore, we used an oligodeoxynucleotide-based
      microarray consisting of 374 human genes, most implicated previously in apoptosis
      or related events, to detect alterations in gene expression in the hippocampus of
      rats subjected to 15 minutes of global cerebral ischemia followed by up to 72
      hours of reperfusion. We found 1.7-fold or greater increases in the expression of
      57 genes and 1.7-fold or greater decreases in the expression of 34 genes at 4,
      24, or 72 hours after ischemia. The number of induced genes increased from 4 to
      72 hours, whereas the number of repressed genes decreased. The induced genes
      included genes involved in protein synthesis, genes mutated in hereditary human
      diseases, proapoptotic genes, antiapoptotic genes, injury-response genes,
      receptors, ion channels, and enzymes. We detected transcriptional induction of
      several genes implicated previously in cerebral ischemia, including ALG2, APP,
      CASP3, CLU, ERCC3, GADD34, GADD153, IGFBP2, TIAR, VEGF, and VIM, as well as other
      genes not so implicated. We also found coinduction of several groups of related
      genes that might represent functional modules within the ischemic neuronal
      transcriptome, including VEGF and its receptor, NRP1; the IGF1 receptor and the
      IGF1-binding protein IGFBP2; Rb, the Rb-binding protein E2F1, and the E2F-related
      transcription factor, TFDP1; the CACNB3 and CACNB4 beta-subunits of the voltage
      gated calcium channel; and caspase-3 and its substrates, ACINUS, FEM1, and GSN.
      To test the hypothesis that genes identified through this approach might have
      roles in the pathophysiology of cerebral ischemia, we measured expression of the
      products of two induced genes not heretofore implicated in cerebral ischemia
      GRB2, an adapter protein involved in growth-factor signaling pathways, and SMN1,
      which participates in RNA processing and is deleted in most cases of spinal
      muscular atrophy. Western analysis showed enhanced expression of both proteins in
      hippocampus at 24 to 72 hours after ischemia, and SMN1 was localized by
      immunohistochemistry to hippocampal neurons. These results suggest that
      microarray analysis of gene expression may be useful for elucidating novel
      molecular mediators of cell death and survival in the ischemic brain.

PMID- 11456316
TI  - Recent advances in our knowledge of the Myxozoa.
AB  - In the last few years two factors have helped to significantly advance our
      understanding of the Myxozoa. First, the phenomenal increase in fin fish
      aquaculture in the 1990s has lead to the increased importance of these parasites;
      in turn this has lead to intensified research efforts, which have increased
      knowledge of the development, diagnosis. and pathogenesis of myxozoans. The
      hallmark discovery in the 1980s that the life cycle of Myxobolus cerebralis
      requires development of an actinosporean stage in the oligochaete. Tubifex
      tubifex, led to the elucidation of the life cycles of several other myxozoans.
      Also, the life cycle and taxonomy of the enigmatic PKX myxozoan has been
      resolved: it is the alternate stage of the unusual myxozoan, Tetracapsula
      bryosalmonae, from bryozoans. The 18S rDNA gene of many species has been
      sequenced, and here we add 22 new sequences to the data set. Phylogenetic
      analyses using all these sequences indicate that: 1) the Myxozoa are closely
      related to Cnidaria (also supported by morphological data); 2) marine taxa at the
      genus level branch separately from genera that usually infect freshwater fishes;
      3) taxa cluster more by development and tissue location than by spore morphology;
      4) the tetracapsulids branched off early in myxozoan evolution, perhaps reflected
      by their having bryozoan, rather than annelid hosts; 5) the morphology of
      actinosporeans offers little information for determining their myxosporean
      counterparts (assuming that they exist); and 6) the marine actinosporeans from
      Australia appear to form a clade within the platysporinid myxosporeans. Ribosomal
      DNA sequences have also enabled development of diagnostic tests for myxozoans.
      PCR and in situ hybridisation tests based on rDNA sequences have been developed
      for Myxobolus cerebralis, Ceratomyxa shasta, Kudoa spp., and Tetracapsula
      bryosalmonae (PKX). Lectin-based and antibody tests have also been developed for
      certain myxozoans, such as PKX and C. shasta. We also review important diseases
      caused by myxozoans, which are emerging or re-emerging. Epizootics of whirling
      disease in wild rainbow trout (Oncorhynchus mykiss) have recently been reported
      throughout the Rocky Mountain states of the USA. With a dramatic increase in
      aquaculture of fishes using marine netpens, several marine myxozoans have been
      recognized or elevated in status as pathological agents. Kudoa thyrsites
      infections have caused severe post-harvest myoliquefaction in pen-reared Atlantic
      salmon (Salmo salar), and Ceratomyxa spp., Sphaerospora spp., and Myxidium leei
      cause disease in pen-reared sea bass (Dicentrarchus labrax) and sea bream species
      (family Sparidae) in Mediterranean countries.

PMID- 11456317
TI  - Purification of GVBD-inducing protein from the ciliate Tetrahymena thermophila.
AB  - Germinal-vesicle-breakdown (GVBD) was induced if a 132,000-g supernatant of
      Tetrahymena thermophila homogenates was injected into Xenopus oocytes. Using this
      induction of GVBD as a bioassay system, a GVBD-inducing substance was purified
      from the Tetrahymena by ultra-filtration, liquid chromatography, and
      electroelution from a band on native-PAGE gel. Proteins eluted from the single
      band on the native-PAGE gel induced GVBD in the absence of oocyte protein
      synthesis. This band resolved into two bands on SDS-PAGE: 60 and 112 kDa. The 60
      kDa protein was the active fraction inducing GVBD. Immunoprecipitation of the 60
      kDa protein prevented the GVBD-inducing activity, supporting the conclusion that
      the 60 kDa protein is the GVBD-inducing substance. An immunoblot with anti-60 kDa
      monoclonal antibody and PSTAIR antibody showed that p13suc1-beads could remove
      cdc2 homologues from T. thermophila supernatant but could not remove the GVBD
      inducing activity. The 60-kDa protein appeared at the same time as micronuclear
      division and disappeared at the beginning of the macronuclear division during
      synchronous cell division. The cyclic appearance of the 60-kDa protein in the T.
      thermophila cell cycle suggests that this protein has a cell cycle function.

PMID- 11456318
TI  - Confusing selective feeding with differential digestion in bacterivorous
      nanoflagellates.
AB  - Food selectivity and the mechanisms of food selection were analyzed by video
      microscopy for three species (Spumella, Ochromonas, Cafeteria) of interception
      feeding heterotrophic nanoflagellates. The fate of individual prey particles,
      either live bacteria and/or inert particles, was recorded during the different
      stages of the particle-flagellate-interaction, which included capture, ingestion,
      digestion, and egestion. The experiments revealed species-specific differences
      and new insights into the underlying mechanisms of particle selection by
      bacterivorous flagellates. When beads and bacteria were offered simultaneously,
      both particles were ingested unselectively at similar rates. However, the
      chrysomonads Spumella and Ochromonas egested the inert beads after a vacuole
      passage time of only 2-3 min, which resulted in an increasing proportion of
      bacteria in the food vacuoles. Vacuole passage time for starved flagellates was
      significantly longer compared to that of exponential-phase flagellates for
      Spumella and Ochromonas. The bicosoecid Cafeteria stored all ingested particles,
      beads as well as bacteria, in food vacuoles for more then 30 min. Therefore
      "selective digestion" is one main mechanism responsible for differential
      processing of prey particles. This selection mechanism may explain some
      discrepancies of former experiments using inert particles as bacterial surrogates
      for measuring bacterivory.

PMID- 11456319
TI  - Sequence diversity and linkage disequilibrium within the merozoite surface
      protein-1 (Msp-1) locus of Plasmodium falciparum: a longitudinal study in Brazil.
AB  - The merozoite surface protein-1 (MSP-1) is a major vaccine candidate for the
      asexual blood stage of malaria. We examined both the extent of sequence diversity
      in block 17, the 3' end of Msp-1 gene coding for a 19-kDa polypeptide (MSP-1(19))
      putatively involved in red blood cell binding, and the patterns of linkage
      disequilibrium between polymorphic sites throughout the Msp-1 locus. The parasite
      population sample consisted of Plasmodium falciparum isolates collected between
      1985 and 1998 in Rondjnia, an area of hypoendemic malaria transmission in the
      southwestern Brazilian Amazon. Results were summarized as follows. (1) Seven
      block-17 sequence variants or haplotypes were found among 130 isolates, including
      two new haplotypes (novel combinations of previously reported amino acid
      replacements), here named Brazil-1 (E-TSR-F) and Brazil-2 (Q-TSR-F). (2) As
      previously shown for other Msp-1 polymorphisms, frequencies of block-17
      haplotypes displayed significant temporal variation. (3) Extensive linkage
      disequilibrium was demonstrated between neighboring dimorphic sites within block
      17, as well as between polymorphisms at the 5' and 3' ends of Msp-1 (map distance
      range: 3.83-4.99 kb). (4) The overall patterns of linkage disequilibrium within
      Msp-1 remained stable over a period of nearly one decade, and examples of
      possible 'epidemic' expansion of parasites carrying particular Msp-1 alleles were
      found in the 1980s and 1990s. These results are discussed in relation to the
      population biology of P. falciparum and the development of malaria vaccines based
      on MSP-1.

PMID- 11456320
TI  - Light microscopic observations of infraciliature and morphogenesis in six species
      of rumen Ostracodinium ciliates.
AB  - Infraciliature and morphogenesis of six rumen ciliates, Ostracodinium mammosum,
      O. munham, O. dilobum, O. rugoloricatum, O. iwawoi, and O. tiete are described
      from pyridinated silver carbonate-impregnated specimens. These six Ostracodinium
      have a similar polybrachykinety arrangement, distinct from that of other
      ophryoscolecid ciliates and intermediate between those of O. gracile and 0.
      damaliscus. Buccal infraciliature is composed of three polybrachykineties, a
      kinety loop, and paralabial kineties. Small dorso-adoral polybrachykinety,
      slender vestibular polybrachykinety, and kinety loop are characteristic. Dorsal
      infraciliature consists of the dorsal polybrachykinety that extends laterally
      along the dorsal side of the body. Morphogenesis is different from that of O.
      gracile, because the right end of ventral primordium extends dorsally to grow
      into a right primordium without separation.

PMID- 11456321
TI  - Molecular evidence for the existence of two species of Marteilia in Europe.
AB  - Marteilia refringens is one of the most significant pathogens of bivalve
      molluscs. Previous sequencing of the small subunit ribosomal RNA gene of M.
      refringens isolates derived from the infected mussels (Mytilus edulis and Mytilus
      galloprovinciallis) and the oyster (Ostrea edulis) in Europe did not reveal
      genetic polymorphisms despite indications from epizootiological data that
      distinct types may exist. We investigated the existence of polymorphisms in the
      internal transcribed spacer region of the ribosomal RNA genes. The sequences of
      this region proved to be clearly dimorphic among Marteilia from five sampling
      sites. The distribution of the two genetic types, named "O" and "M", appeared to
      be linked to the host species, oysters and mussels, respectively. We therefore
      support the recognition of two species of Marteilia in Europe and propose that
      the "O" type corresponds to M. refringens and the "M" type to M. maurini.

PMID- 11456322
TI  - The rumen ciliate fauna of domestic sheep (Ovis ammon aires) from the Turkish
      Republic of Northern Cyprus.
AB  - Concentration and composition of ciliate protozoa in the families
      Ophryoscolecidae and Isotrichidae were determined in rumen contents of domestic
      sheep (Ovis ammon aries) from Cyprus. A total of five genera of Ophryoscolecidae
      were identified, Metadinium, Enoploplastron, Polyplastron, Epidinium, and
      Ophrvoscolex, which included six species: Metadinium affine, Enoploplastron
      triloricatum, Polyplastron multivesiculatum, Epidinium ecaudatum, Epidinium
      graini, and Ophryoscolex purkynjei. Eight separate forms of Epidinium were
      identified (E. ecaudatum f. ecaudatum, E. e. f. caudatum, E. e. f. bicaudatum, E.
      e. f. tricaudatum, E. e. f. quadricaudatum, E. graini f. graini, E. g. f.
      caudatricoronatum, and E. g. f. caudaquadricoroniatum), along with five forms of
      Ophryoscolex purkynjei (O. p. f. purkynjei, O. p. f. bifidobicinctus, O. p. f.
      bifidoquadricinctus, O. p. f. bicoronatus, O. p. f. tricoronatus, and O. p. f.
      quadricoronatus). Three species of Isotrichidae were observed, Isotricha
      intestinalis, I. prostoma, and Dasytricha ruminantium. This study reports new
      host records for three forms of Epidinium graini and Ophryoscolex purkynjei f.
      bifidobicinctus. The rumen fauna in the family Ophryoscolecidae from Cypriote
      domestic sheep appear to have limited diversity compared to those from Turkish
      and Far Eastern (Chinese/Japanese) sheep, while they are more diverse than those
      found in Western European (Scottish) and North American (Canadian/Alaskan) sheep.

PMID- 11456323
TI  - In vivo and in vitro development of the protist Helicosporidium sp.
AB  - We describe the discovery and developmental features of a Helicosporidium sp.
      isolated from the black fly Simulium jonesi. Morphologically, the helicosporidia
      are characterized by a distinct cyst stage that encloses three ovoid cells and a
      single elongate filamentous cell. Bioassays have demonstrated that the cysts of
      this isolate infect various insect species, including the lepidopterans,
      Helicoverpa zea, Galleria mellonella, and Manduca sexta, and the dipterans, Musca
      domestica, Aedes taeniorhynchus, Anopheles albimanus, and An. quadrimaculatus.
      The cysts attach to the insect peritrophic matrix prior to dehiscence, which
      releases the filamentous cell and the three ovoid cells. The ovoid cells are
      short-lived in the insect gut with infection mediated by the penetration of the
      filamentous cell into the host. Furthermore, these filamentous cells are covered
      with projections that anchor them to the midgut lining. Unlike most
      entomopathogenic protozoa, this Helicosporidium sp. can be propagated in simple
      nutritional media under defined in vitro conditions, providing a system to
      conduct detailed analysis of the developmental biology of this poorly known
      taxon. The morphology and development of the in vitro produced cells are similar
      to that reported for the achorophyllic algae belonging to the genus Prototheca.

PMID- 11456324
TI  - Genetic diversity in the microsporidian Encephalitozoon hellem demonstrated by
      pulsed-field gel electrophoresis.
AB  - Encephalitozoon hellem is a microsporidian species responsible for opportunistic
      infections in AIDS patients. Use of a novel chitinase-based method allowed
      unsheared chromosomal DNA to be recovered from eleven E. hellem isolates derived
      from three geographic regions. All isolates were typed by 18S rDNA sequencing,
      which showed that they belonged to intemal transcribed spacer type 1. After
      ethidium bromide staining, pulsed-field gel electrophoresis (PFGE) analysis
      discriminated two new karyotypes comprising 7 and 8 chromosomal bands
      respectively, ranging in size from 205- to 272-kb pairs. Genomic size was
      estimated to be 2.39 Mb. Our data indicate PFGE is useful for typing E. hellem
      and confirms genetic diversity among E. hellem genotypes.

PMID- 11456325
TI  - Seasonal variability in abundance and diversity of soil gymnamoebae along a short
      transect in southeastern USA.
AB  - The abundance and diversity of gymnamoebae in three subsoils varying in
      compaction and water retention along a 1.2 m transect were documented as the
      local climatic conditions changed from late summer 1999 through mid-summer 2000.
      The mean density of gymnamoebae for the loose soil (1,655/g) was greater than
      either the most compact (1,468/g) or moderately compact soil (851/g). Minimum
      densities occurred in middle and late summer for all soils while significant (F =
      38.803, < or = 0.0002) density peaks at 3.212/g occurred in early summer in the
      most compact soil, 2.928/g in the least compact, and 2,209/g in the moderately
      compact soil. Limax non-eruptive gymnamoebae (mt 2) correlated (r = 0.49, p < or
      = 0.016) with moisture while eruptive limax gymnamoebae ( 3) correlated with
      temperature (r = 0.07, p < or = 0.024), moisture (r = 0.58, p < or = 0.001) and
      precipitation (r = 0.46, p < or = 0.029). Flattened or discoid amoebae (mt 4)
      dominated throughout most of the survey, and the two limax groups showed inverse
      relationships. Chi-square analyses showed significant differences in the numbers
      of limax eruptive gymnamoebae compared to all other morphotypes on all but one
      sampling period.

PMID- 11456326
TI  - On core jakobids and excavate taxa: the ultrastructure of Jakoba incarcerata.
AB  - The cellular organisation of the 'excavate' flagellate Jakoba incarcerata
      Bernard, Simpson and Patterson 2000 is described. Cells have one nucleus and
      dictyosome. The putative mitochondria lack cristae. Two flagella (anterior and
      posterior) insert anterior to the feeding groove. The posterior flagellum bears a
      dorsal vane. An 'anterior' microtubular root arises against the anterior basal
      body. Two main microtubular roots, left and right, and a singlet 'root' arise
      around the posterior basal body and support the groove. Non-microtubular fibres
      termed 'A', 'B', 'I', and 'composite' associate with the right root. A
      multilaminar 'C' fibre associates with the left root. The cytoskeleton of J.
      incarcerata indicates a common ancestry with other excavate taxa (i.e.
      diplomonads, retortamonads, heteroloboseids, 'core jakobids', Malawimonas,
      Carpediemonas, and Trimastix). Overall, J. incarcerata is most similar to (other)
      core jakobids, namely Jakoba libera, Reclinomonas, and Histiona. We regard J.
      incarcerata as a core jakobid and identify the group by the synapomorphy 'vanes
      restricted to dorsal side of the posterior flagellum'. The anterior root and
      position of the B fibre (and presence of dense inclusions in the cartwheels and a
      conscpicuous singlet root-associated fibre) in J. incarcerata are novel for core
      jakobids and argue for close relationships with Trimastix and/or Heterolobosea.
      The C fibre is similar in substructure to the costal fibre of parabasalids and it
      is possible that the structures are homologous.

PMID- 11456327
TI  - Archaebacterial relationships of the phosphoenolpyruvate carboxykinase gene
      reveal mosaicism of Giardia intestinalis core metabolism.
AB  - A gene encoding a putative GTP-specific phosphoenolpyruvate carboxykinase has
      been cloned and sequenced from the type I amitochondriate protist Giardia
      intestinalis. The deduced amino acid sequence is related most closely to homologs
      from hyperthermophilic archaebacteria and only more distantly to homologs from
      Eubacteria and Metazoa. Most enzymes of Giardia core metabolism, however, are
      related more closely to eubacterial and metazoan homologs. An archaebacterial
      relationship has been noted previously for the unusual acetyl-CoA synthetase (ADP
      forming) of this organism. The results suggest that phosphoenolpyruvate
      carboxykinase and acetyl-CoA synthetase have been acquired from different sources
      than most enzymes of Giardia core metabolism.

PMID- 11456328
TI  - Phylogenetic position of the trichomonad parasite of turkeys, Histomonas
      meleagridis (Smith) Tyzzer, inferred from small subunit rRNA sequence.
AB  - The phylogenetic position of the trichomonad, Histomonas meleagridis was
      determined by analysis of small subunit rRNAs. Molecular trees including all
      identified parabasalid sequences available in data bases were inferred by
      distance, parsimony, and likelihood methods. All reveal a close relationship
      between H. meleagridis, and Dientamoeba fragilis. Moreover, small subunit rRNAs
      of both amoeboid species have a reduced G + C content and increased chain length
      relative to other parabasalids. Finally, the rRNA genes from H. meleagridis and
      D. fragilis share a recent common ancestor with Tritrichomonasfoetus, which
      exhibits a more developed cytoskeleton. This indicates that Histomonas and
      Dientamoeba secondarily lost most of the typical trichomonad cytoskeletal
      structures and hence, do not represent primitive morphologies. A global phylogeny
      of parabasalids revealed significant discrepancies with morphology-based
      classifications, such as the polyphyly of most of the parabasalid families and
      classes included in our study.

PMID- 11456329
TI  - Two fatal cases of adenovirus-related illness in previously healthy young adults-
      Illinois, 2000.
AB  - Adenoviruses are common pathogens that often are associated with respiratory and
      gastrointestinal illness and/or conjunctivitis in young persons. Adenovirus
      serotypes 4 and 7 have caused outbreaks of self-limited febrile respiratory
      illness in young adults in basic military training. During the 1950s and 1960s,
      up to 10% of recruits were infected with adenovirus, and these pathogens were
      responsible for approximately 90% of pneumonia hospitalizations. Beginning in
      1971, all military recruits received oral, live, enteric-coated vaccines that
      were licensed by the Food and Drug Administration as safe and effective in
      preventing illness from adenovirus serotypes 4 and 7. In 1996, the sole
      manufacturer ceased production of adenoviral vaccines and, as supplies dwindled
      during the next few years, outbreaks of adenoviral respiratory illness reemerged
      in military settings. Since 1999, approximately 10%-12% of all recruits have
      become ill with adenovirus infection in basic training, similar to the prevaccine
      era. This report describes the first two deaths probably associated with
      adenovirus infection identified in military recruits since the vaccines became
      unavailable. The military has requested proposals for a new adenovirus vaccine
      manufacturer; however, these deaths suggest that efforts by policymakers and
      pharmaceutical companies to reestablish adenoviral vaccine production should be
      intensified.

PMID- 11456330
TI  - Health-related quality of life--Los Angeles County, California, 1999.
AB  - The overall goals of the national health objectives for 2010 are to increase the
      quality and years of healthy life and eliminate health disparities in the U.S.
      population. To assess progress in achieving these goals, the Behavioral Risk
      Factor Surveillance System (BRFSS) includes a core set of four health-related
      quality of life (HRQOL) questions that have been used since 1993 to track adults'
      perceptions of their physical and mental health and level of function. Data on
      HRQOL have been reported nationwide and by state but typically not at the county
      or community level. This report summarizes findings of the 1999-2000 Los Angeles
      County Health Survey (LACHS) on HRQOL in the county's adult population and
      describes variations in HRQOL across population groups in the county. The
      findings have been published in a county health report and are being used by
      public health officials to highlight the significant disparities in HRQOL across
      demographic and socioeconomic populations in Los Angeles County and to guide
      program planning and resource allocation decisions.

PMID- 11456331
TI  - Outbreak of listeriosis associated with homemade Mexican-style cheese--North
      Carolina, October 2000-January 2001.
AB  - On November 13, 2000, health-care providers at a hospital in Winston-Salem, North
      Carolina, contacted the local health department about three cases of listeriosis
      within a 2-week period in recent Mexican immigrants. The North Carolina General
      Communicable Disease Control Branch, in collaboration with the Forsyth County
      Health Department, the North Carolina Departments of Agriculture and Consumer
      Services (NCDA&CS) and Environment and Natural Resources, the Food and Drug
      Administration (FDA), and CDC investigated this outbreak of Listeria
      monocytogenes infections. This report summarizes the results of the
      investigation, which implicated noncommercial, homemade, Mexican-style fresh soft
      cheese produced from contaminated raw milk sold by a local dairy farm as the
      causative agent. Culturally appropriate education efforts are important to reduce
      the risk for L. monocytogenes transmission through Mexican-style fresh soft
      cheese.

PMID- 11456332
TI  - Delta activity as an early indicator for soman-induced brain damage: a review.
AB  - The organophosphorus (OP) compound soman is known to produce long-lasting
      epileptic seizure activity and associated brain damage. The present paper reviews
      the findings of five recent studies that tentatively established correlations
      between the development of soman-induced neuropathology and some subtle changes
      in the electrocortigraphic (ECoG) power spectrum. It is important to note that
      the reported experiments have been performed independently by three different
      teams (France, The Netherlands, USA) in various animal models (rat, guinea-pig,
      cynomolgus monkey) through different protocols of intoxication, pharmacological
      environments, and methods for ECoG spectral analysis. Despite these disparities,
      the five studies show that a suistained shift of ECoG power toward the lowest
      frequency range, i.e. the delta band, occurs within the first hours of soman
      induced seizures. This early ECoG spectral change is concurrent with the first
      neuropathological changes in brain and is almost constantly followed, days or
      weeks later, by at least minimal neuropathology. Moreover the relative
      contribution of delta activity to the ECoG power spectrum still remains
      abnormally high for 1-3 days after seizure onset, i.e. within the phase of damage
      maturation. On the other hand, somnan-induced neuropathology was not observed in
      non-seizuring animals in which the delta activity was not increased above the pre
      soman baseline. Similarly, no brain damage was ever shown in seizuring subjects
      in which the initial delta change eventually normalized after the curative
      administration of efficient anticonvulsant drugs such as the non-competitive
      antagonists of the NMDA receptor. These results, in agreement with previously
      published observations, strongly suggest that an increase of the relative power
      in the delta band might be a real-time marker of the ongoing development of soman
      induced, seizure-related cerebral lesions and a reliable predictor for the final
      neuronal losses to come. Therefore, the monitoring of delta activity during the
      24-72 h period that follows soman exposure may potentially be a useful tool to
      follow "on-line" the progression of brain damage and to control the
      neuroprotective activity of'a medication. Moreover since the method is non
      invasive in man and since the above-presented results have been partly found in
      primates, the applicability of spectral analysis as a prognostic means in human
      OP poisoning ought to be seriously considered.

PMID- 11456333
TI  - Methylmercury neurotoxicity in cultures of human neurons, astrocytes,
      neuroblastoma cells.
AB  - Neurotoxic effects of methylmercury, were investigated in vitro in primary
      cultures of human neurons and astrocytes isolatedfrom human fetal brain and in
      the human neuroblastoma cell line SH-SY5Y. The protection provided by agents with
      antioxidant properties was tested in these cultures to examine the oxidative
      stress mechanism of methylmercury poisoning. After 24 h of exposure to
      methylmercury, LC50 values were 6.5, 8.1 and 6.9 microM for human neurons,
      astrocytes and neuroblastoma cells, respectively, and the degree of cell damage
      increased at longer exposure times. Depletion of the cellular pool of reduced
      glutathione (GSH) by treatment with buthionine sulfoximine potentiated
      methylmercury cytotoxicity in all three cell types; neuroblastoma cells were the
      most sensitive. Addition of GSH extracellularly blocked methylmercury
      neurotoxicity in all cell types. The major beneficial effect of GSH could be
      attributed to its capacity to form conjugates with methylmercury, which reduces
      the availability of these organometallic molecules to the cells and facilitates
      their efflux. Cysteine protected astrocytes and neuroblastoma cells from
      methylmercury neurotoxicity, while selenite, Vitamin E and catalase produced some
      minor protective effects in three cell types, particularly in neurons. The
      present study showed that the human neural cells tested had differential
      responses to methylmercury: astrocytes were resistant to methylmercury
      neurotoxicity and neurons were more most responsive to protection afforded by
      antioxidants among the three cell types.

PMID- 11456334
TI  - Interaction of tetramethrin and deltamethrin at the single sodium channel in rat
      hippocampal neurons.
AB  - Type I and type II pyrethroids are known to modulate the sodium channel to cause
      persistent openings during depolarization and upon repolarization. Although there
      are some similarities between the two types of pyrethroids in their actions on
      sodium channels, the pattern of modification of sodium currents is different
      between the two types of pyrethroids. In the present study, interactions of the
      type I pyrethroid tetramethrin and the type II pyrethroid deltamethrin at rat
      hippocampal neuron sodium channels were investigated using the inside-out single
      channel patch clamp technique. Deltamethrin-modified sodium channels opened much
      longer than tetramethrin-modified sodium channels. When 10 microM tetramethrin
      was applied to membrane patches that had been exposed to 10 microM deltamethrin,
      deltamethrin-modified prolonged single sodium currents disappeared and were
      replaced by shorter openings which were characteristic of tetramethrin-modified
      channel openings. These single-channel data are compatible with previous whole
      cell competition study between type I and type II pyrethroids. These results are
      interpreted as being due to the displacement of the type II pyrethroid molecule
      by the type I pyrethroid molecule from the same binding site or to the allosteric
      interaction of the two pyrethroid molecules at separate sodium channel sites.

PMID- 11456335
TI  - Metabolism, toxicokinetics and hemoglobin adduct formation in rats following
      subacute and subchronic acrylamide dosing.
AB  - Long-term, low-dose (subchronic) oral acrylamide (ACR) exposure produces
      peripheral nerve axon degeneration, whereas irreversible axon injury is not a
      component of short-term, higher dose (subacute) i.p. intoxication [Toxicol Appl
      Pharmacol 1998;151:211]. It is possible that this differential axonopathic
      expression is a product of exposure-dependent differences in ACR
      biotransformation and/or tissue distribution. Therefore, we determined the
      toxicokinetics and metabolism of ACR following subchronic oral (2.8 mM in
      drinking water for 34 days) or subacute i.p. (50 mg/kg per day for 11 days)
      administration to rats. Both dosing regimens produced moderate levels of
      behavioral neurotoxicity and, for each, ACR was rapidly absorbed from the site of
      administration and evenly distributed to tissues. Peak ACR plasma concentrations
      and tissue levels were directly related to corresponding daily dosing rates (20
      or 50 mg/kg per day). During subchronic oral dosing a larger proportion (30%) of
      plasma ACR was converted to the epoxide metabolite glycidamide (GLY) than was
      observed following subacute i.p. intoxication (8%). This subchronic effect was
      not specifically related to changes in enzyme activities involved in GLY
      formation (cytochrome P450 2E1) ormetabolism (epoxide hydrolases). Both ACR and
      GLY formed hemoglobin adducts during subacute and subchronic dosing, the absolute
      quantity of which did not change as a function of neurotoxicant exposure.
      Compared to subacute i.p. exposure, the subchronic schedule produced
      approximately 30% less ACR adducts but two-fold more GLY adducts. GLY has been
      considered to be an active ACR metabolite and might mediate axon degeneration
      during subchronic ACR administration. However, corresponding peak GLY plasma
      concentrations were relatively low and previous studies have shown that GLY is
      only a weak neurotoxicant. Our study did not reveal other toxicokinetic
      idiosyncrasies that might be a basis for subchronic induction of irreversible
      axon damage. Consequently the mechanism of axon degeneration does not appear to
      involve route- or rate-dependent differences in metabolism or disposition.

PMID- 11456336
TI  - Soman-induced interleukin-1 beta mRNA and protein in rat brain.
AB  - Exposure to high doses of the toxic organophosphate compound soman, also known as
      a chemical warfare agent, causes a progression of toxic symptoms including hyper
      secretions, convulsions, respiratory depression, and finally death. In previous
      studies, we have demonstrated pronounced effects following soman intoxication in
      dopaminergic, GABAergic, and cholinergic systems in rat brain. The aim of this
      study was to investigate the effects on the pro-inflammatory cytokine interleukin
      1beta (IL-1beta), indicated as mRNA and protein production, at different time
      intervals following soman intoxication. The peak levels of mRNA was observed 30
      min following soman exposure, while a significant increase in the protein was
      observed at 6 h. Immunohistochemistry analysis revealed the presence of IL-1beta
      protein in astrocytes and endothelial cells. In addition to the previously
      observed effects of soman, there is an induction of IL-1beta in the brain. This
      effect, which is highly correlated to convulsions, implicates IL-1beta as a
      possible mediator for long-term brain damage observed after soman intoxication.

PMID- 11456337
TI  - 2-Halopropionic acid-induced cerebellar granule cell necrosis in the rat: in vivo
      and in vitro studies.
AB  - Daily oral administration of 2.3 mmol/kg L-2-chloropropionic acid (L-2-CPA), DL-2
      bromopropionic acid (2-BPA) or DL-2-iodopropionic acid (2-/PA) but not DL-2
      fluoropropionic acid (2-FPA) produced cerebellar granule cell necrosis in the
      rat. Twenty four hours after three doses of L-2-CPA or two doses of 2-BPA,
      animals showed clinical signs of motor incoordination and reduced hindlimb
      function which was associated with marked cerebellar oedema and cerebellar
      granule cell necrosis. Biochemical analyses showed a marked increase in
      cerebellar water and Na+ content, and a reduction in cerebellar glutamate and
      aspartate. 2-IPA at this dose was toxic, the animals not surviving a second dose,
      histopathology showed hepatic and renal necrosis with mild cerebellar granule
      cell necrosis. 2-FPA was not neurotoxic after four daily doses. A marked decrease
      in hepatic and cerebellar non-protein sulphydryl (NP-SH) content was observed 4 h
      after a single dose of 2.3 mmol/kg L-2-CPA, 2-BPA and 2-IPA but not 2-FPA. Daily
      doses of 2-BPA for 3 days produced a sustained 50% depletion in cerebellar NP-SH.
      In vitro, L-2-CPA, 2-BPA and 2-IPA produced glutathione (GSH) depletion in the
      presence of rat liver cytosol, while 2-FPA did not. Depletion of GSH in the
      presence of cerebellar cytosol was only observed with 2-IPA. Studies using
      primary cultures of rat cerebellar granule cells, showed that all analogues
      produced a concentration dependent loss of cell viability. Mean EC50 values for 2
      FPA, L-2-CPA, 2-BPA and 2-IPA toxicity were 1.7, >10, 0.5 and 0.3 mM,
      respectively, for 24 h continuous exposure. MK-801 and Vitamin E afforded
      protection against L-2-CPA-induced cytotoxicity but not against the other
      analogues. In summary, in addition to L-2-CPA, both 2-BPA and 2-IPA produce
      cerebellar granule cell necrosis in the rat. Depletion of GSH in the cerebellum
      may be contributory factor in the cascade of events leading to neurotoxicity.

PMID- 11456338
TI  - Neurotoxicological effects associated with short-term exposure of Sprague-Dawley
      rats to hydrogen sulfide.
AB  - Although hydrogen sulfide (H2S) is a known neurotoxic hazard, only a limited
      number of experimental animal studies have examined its neurochemical or
      behavioral effects. Our aim was to determine if short-term inhalation exposure of
      rats to H2S would result in altered brain catecholamnine levels or impaired
      learning and memory. Three groups of adult male CD rats were tested; two groups
      were exposed by nose-only inhalation (0, 30, 80, 200, or 400 ppm H2S) and one
      group was exposed by whole-body inhalation (0, 10, 30, or 80 ppm H2S) for 3 h per
      day forfive consecutive days. The first group (n = 10 rats per concentration) was
      tested immediately following each daily nose-only H2S exposure for spatial
      learning with a Morris water maze. Core body temperatures were also monitored in
      these animals during and after the last H2S exposure. The second group of rats (n
      = 10 rats per concentration) was tested for spontaneous motor activity
      immediately following the fifth exposure. These rats were then euthanized and
      striatal, hippocampal, and hindbrain catecholamnine levels determined. A third
      group of rats (n = 5-7 rats per concentration) was pretrained on a multiple fixed
      interval (FI) schedule and exposed whole-body. Daily performance on the FI
      schedule was compared for the week pre-exposure, for the exposure week
      immediately following daily exposures, and for the week postexposure. We observed
      significant reductions in motor activity, water maze performance, and body
      temperature following exposure only to high concentrations (> or = 80 ppm) of
      H2S. Exposure to H2S did not affect regional brain catecholamine concentrations
      or performance on the FI schedule. Additional studies using other measures of
      behavior and longer-term exposure to H2S may be required to more definitively
      address conditions under which H2S exposure results in behavioral toxicity.

PMID- 11456339
TI  - Non invasive quantification of manganese deposits in the rat brain by local
      measurement of NMR proton T1 relaxation times.
AB  - Up to now, there is no reliable non invasive biomarker for the concentration of
      manganese (Mn) in the brain after intoxication to this metal. The aim of the
      present experimental study was to determine the predictive value of the localized
      measurement of the proton NMR relaxation time T1 as a quantitative estimation of
      the concentration of Mn in brain. The relationship of the proton relaxation rates
      (1/T1) was established in rat brain homogenates as a function of the Mn, iron,
      and copper concentration. Subsequently, an experimental model of Mn neurotoxicity
      was used: rats were stereotactically injected with increasing amounts of Mn2+ (as
      MnCl2) in the ventricles. After 3 weeks, local measurements of T1 were carried
      out in live rats. They were then sacrificed in order to sample the striatum, the
      cortex, and the cerebellum from the brain and to perform a quantitative
      determination of the concentration of Mn in these tissues by atomic absorption
      spectrometry (AAS). The results indicate excellent correlation coefficients
      between relaxation rates and tissue Mn concentrations (r= 0.84, 0.77 and 0.92 for
      the striatum, the cortex and the cerebellum, respectively). This methodology
      offers a unique toolfor monitoring the degree of Mn concentration in different
      areas of the brain in animal models of Mn intoxication. It will be useful for
      evaluating the efficacy of treatments aimed at decreasing the metal in the brain.
      The method could be potentially useful for being transposed in the clinical
      situation for monitoring Mn-exposed workers.

PMID- 11456340
TI  - Neurophysiologic effects of chemical agent hydrolysis products on cortical
      neurons in vitro.
AB  - The neurophysiologic effects of chemical agent hydrolysis products were examined
      on cultured cortical neurons using multielectrode array (MEA) recording and the
      whole-cell patch clamp technique. Measurement of neuronal network extracellular
      potentials showed that the primary hydrolysis product of soman, pinacolyl
      methylphosphonic acid (PMPA), inhibited network mean burst and spike rates with
      an EC50 of approximately 2 mM. In contrast, the degradation product of sarin,
      isopropyl methylphosphonic acid (IMPA), and the final common hydrolysis product
      of both soman and sarin, methylphosphonic acid (MPA), failed to affect neuronal
      network behavior at concentrations reaching 5 mM. Closer examination of the
      effects of PMPA (2 mM) on discriminated extracellular units revealed that mean
      spike amplitude was slightly diminished to 95 +/- 1% (mean +/- S.E.M., n = 6, P <
      0.01) of control. Whole-cell patch clamp records under current clamp mode also
      showed a PMPA-induced depression of the firing rate of spontaneous action
      potentials (APs) to 36 +/- 6% (n = 5, P < 0.001) of control. In addition, a minor
      depression with exposure to PMPA was observed in spontaneous and evoked AP
      amplitude to 93 +/- 3% (n = 5, P < 0.05) of control with no change in either the
      baseline membrane potential or input resistance. Preliminary voltage clamp
      recordings indicated a reduction in the occurrence of spontaneous inward currents
      with application of PMPA. These findings suggest that PMPA, unlike MPA or IMPA,
      may more readily interfere with one or more aspects of excitatory synaptic
      transmission. Furthermore, the data demonstrate that the combination of
      extracellular microelectrode array and patch clamp recording techniques
      facilitates analysis of compounds with neuropharmacologic effects.

PMID- 11456341
TI  - Blood levels of toxic and essential metals in motor neuron disease.
AB  - Toxic and essential metals have been implicated in the pathogenesis of sporadic
      motor neuron disease (SMND), but attempts to measure blood levels of these metals
      have led to contradictory results. We, therefore, measured blood levels of
      various metals using paired SMND/controls. In 20 subjects with SMND (15 males,
      five females, mean age 56.8 years) and 20 partner controls (15 females, five
      males, mean age 55.0 years) cadmium, lead, mercury, copper, zinc and selenium
      levels were measured in blood, plasma and red cells with inductively coupled
      plasma mass spectrometry and manganese levels with atomic absorption
      spectrophotometry. Results were analysed using non-parametric tests. Hypo-osmotic
      red blood cellfragility was estimated in six SMND/control pairs to see if
      hemolysis could account for increased metal levels. The plasma cadmium level was
      significantly raised in SMND cases (P = 0.005), but with considerable overlap
      between SMND and controls. No other metal levels were significantly different,
      though plasma lead in SMND had a tendency to be higher than controls. No
      difference in red cell fragility was found between groups. In conclusion, plasma
      levels of cadmium were raised in this SMND group, but the biological significance
      of this is uncertain. The measurement of metals in the blood of SMND cases seems
      unwarrranted for routine diagnostic testing.

PMID- 11456342
TI  - Caries in populations--a theoretical, causal approach.
AB  - The focus of this paper is caries in populations. Caries is assessed as a
      phenomenon and as it occurs in populations. It is observed that in recent
      literature the notion of causation of caries is restricted to the biological
      process on the tooth surface. This may be sufficient to explain caries as a
      phenomenon, but it is argued that a biological causation is insufficient in order
      to understand caries and its variation in populations. The understanding of the
      determinants of a population's oral health has been seriously impeded by the
      absence of a theoretical framework. A framework would be useful to the extent
      that it would bridge relevant categories for portraying complex causal patterns
      of caries in populations. An approach to a framework has therefore been outlined,
      and the idea of such a framework has been confronted with three critical
      comments. The framework is as yet pragmatic, incomplete, uncertain and
      fragmented. Yet, even such an approach may invite greater precision in
      epidemiological concepts about causes of caries than presently prevails. The
      framework directs attention to health effects of collective phenomena that cannot
      be reduced to individual attributes. The image proposed in this paper is intended
      to spur discussion about important aspects of the epidemiology of caries in
      populations.

PMID- 11456343
TI  - Age-period-cohort analysis of dentist use in Spain from 1987 to 1997. An analysis
      based on the Spanish National Health Interview Surveys.
AB  - The aim was to determine whether the effects of age, period (from 1987 to 1997),
      or cohort (birth-cohort) are the most plausible explanations for the variation in
      dentist utilisation over time in Spain. On the basis of three sequential Spanish
      National Health Surveys, the trend in the percentage of people visiting the
      dentist within the previous 3 months was analysed by means of a standard cohort
      table and by the CLAYTON & SCHIFFLERS method. The percent of people visiting the
      dentist grew from 13.6% in 1987, to 17.2% in 1997. Visual examination of the
      cohort table, together with the fit of the age-cohort model, indicates that
      cohort succession may be the best explanation for the increase. The younger the
      cohort, the higher the dental visit rate; this relationship was strongest for
      people born after 1977. The model also indicates that the rates of dental
      visiting tend to increase up to middle age, and then tend to decrease with age.

PMID- 11456344
TI  - Oral status indicators DMFT and FS-T: reflections on index selection.
AB  - Oral status in a population has traditionally been described by the DMFT index
      (decayed, filled, and missing teeth). There seems to be contradicting and
      confusing evidence in the literature with regard to the usefulness of different
      indices. Limitations of the DMFT are recognised, and attempts have been made to
      develop other indices. Two indices, DMFT and FS-T (filled and sound teeth) have
      been selected for analysis in the present paper. The purpose of this paper is to
      examine the relationship between DMFT and FS-T in different populations, and to
      show consequences of choice of index exemplified in analytical analysis. Data
      stem from the Trondelag-83 and -94 studies that were follow-up studies of the
      Norwegian portion of the 1973 International Collaborative Study. Sunflower
      scatter plots and regression analyses were used to describe the variation in DMFT
      and FS-T in different populations. DMFT was more suitable for describing
      variation in populations with low levels of disease than FS-T, while FS-T was
      more suitable for describing variation in populations with high levels of
      disease. It may be concluded that both DMFT and FS-T should be presented when
      describing oral status in a population. However, choice of index depends first of
      all on the purpose of the investigation. If there are theoretical reasons to
      prefer one index instead of the other, the superiority of the alternative index
      in terms of variation must be disregarded.

PMID- 11456345
TI  - Controlled study of EMG activity of the jaw closers and openers during
      mastication in patients with myasthenia gravis.
AB  - Mastication was evaluated in patients with bulbar myasthenia gravis and compared
      with that of patients with ocular myasthenia gravis, patients in remission who
      previously suffered from bulbar symptoms, and healthy controls. Bulbar myasthenia
      gravis may impair mastication due to weakness of the masticatory muscles. The aim
      of the study was to objectively evaluate the influence of myasthenia gravis on
      mastication. The subjects chewed a piece of breakfast cake and chewed 1 min on a
      piece of chewing gum. Surface EMG of the masseter muscle, temporalis muscle and
      jaw opener muscles was recorded. Statistical analysis revealed that bulbar
      patients produced significantly less EMG activity in the closing phase of a
      chewing cycle in both experiments. The EMG of the masseter muscle expressed as
      percentage of the maximum EMG during maximal clenching showed significantly
      higher values in the bulbar group than in the other groups. This was not found
      for the temporalis muscle. It was suggested that bulbar patients use a strategy
      of limited effort to produce a bolus that can be swallowed. The ocular patients
      and the patients in remission showed no subclinical impairments in muscle
      function during chewing.

PMID- 11456346
TI  - Psychological distress in chronic craniomandibular and cervical spinal pain
      patients.
AB  - Recent studies to chronic pain have shown that the number of painful body areas
      is related to the level of psychological distress. Therefore, the first aim of
      this study was to analyse differences in level of psychological distress between
      craniomandibular pain patients with or without cervical spinal pain. In this
      analysis, the number of painful body areas below the cervical spine was also
      taken into account. The second aim was to determine psychological differences
      between subgroups of craniomandibular pain patients. In this study, 103 out of
      250 persons with or without craniomandibular pain were included in the final
      analyses. Patients who suffered from both craniomandibular and cervical spinal
      pain showed higher levels of psychological distress, as measured with the Symptom
      Checklist 90 (SCL-90) than patients with local craniomandibular pain and persons
      without pain. Further, a positive relationship was found between the number of
      painful body areas below the cervical spine, as measured on a body drawing, and
      the SCL-90 scores. No psychological differences were found between myogenous and
      arthrogenous craniomandibular pain patients. In conclusion, chronic
      craniomandibular pain patients with a coexistent cervical spinal pain showed more
      psychological distress compared to patients with only a local craniomandibular
      pain and asymptomatic persons.

PMID- 11456347
TI  - Psychophysiological reactions in dental phobic patients during video stimulation.
AB  - Electromyography (EMG) reflecting forehead muscle tension, heart rate (HR) and
      skin conductance (SC) were continuously recorded in dental phobic subjects (n =
      126) and controls (n = 25) during exposure of dental and neutral video scenes in
      order to explore the relationship between dental fear and psychophysiological
      responses. This relationship is far from well established, and the present
      investigation was performed to contribute to the understanding of the
      psychophysiology of dental fear. Dental phobics had a mean anxiety level of 17.3
      as measured by Corah's Dental Anxiety Scale (DAS) and refused conventional dental
      treatment. Control subjects reported regular dental treatment and a DAS score
      below population average (DAS < 8). Psychophysiological data was reduced to level
      (mean) and reactivity (means of intraindividual variations). Results showed that
      physiologic reactions to fear-relevant conditions measured by HR and EMG
      reflected degree of dental fear, and that neutral conditions, when presented for
      the second and third time, induced lower psychophysiologic reactions in phobics
      than in controls. Recordings of SC indicated that dental phobics may differ from
      individuals suffering from other types of specific phobia by showing weakened
      autonomic responsiveness to threat.

PMID- 11456348
TI  - A comparative study on the use of Bio-Oss and enamel matrix derivative (Emdogain)
      in the treatment of periodontal bone defects.
AB  - The aim of the study was to evaluate the clinical and radiographic outcome
      following two different techniques of periodontal bone defects treatment. The
      study included 24 generally healthy subjects with advanced periodontitis. The
      patients were divided into two equal groups, according to the method applied. In
      the first group, a bovine-derived hydroxyapatite xenograft (Bio-Oss) combined
      with a resorbable collagen membrane (Bio-Gide) was used. The other group was
      treated with enamel matrix derivative (Emdogain). Clinical and radiographic
      examinations were performed prior to and 1 yr after surgery. The following
      parameters were evaluated: plaque index, gingival index, probing pocket depth,
      clinical attachment level, gingival recession, radiographic defect depth, and
      defect width. All clinical and radiographic parameters (except plaque index and
      gingival recession) were significantly reduced after treatment in both groups. No
      differences were revealed between the two groups of patients in examined
      parameters after treatment. The results demonstrated that the treatment of
      periodontal bone defects with both techniques leads to similar and significant
      improvements in clinical and radiographic parameters.

PMID- 11456349
TI  - Effect of fluoride on glucose incorporation and metabolism in biofilm cells of
      Streptococcus mutans.
AB  - The aim of this study was two-fold: firstly, to study the effect of high fluoride
      concentrations on carbohydrate metabolism in Streptococcus mutans present in
      biofilms on hydroxyapatite; and, secondly, to evaluate the effect of fluoride
      bound hydroxyapatite on lactic acid formation in growing biofilms of Strep.
      mutans. Biofilms of a clinical strain of Strep. mutans on saliva-coated
      hydroxyapatite beads were incubated with sodium fluoride over a wide range of
      concentrations. At high fluoride concentrations (>10 mM) the incorporation of
      [14C]-labeled glucose decreased by 80-85%, at both pH 7.0 and 5.6. At lower
      fluoride concentrations, the effect of fluoride on the incorporation of labeled
      glucose was pH-dependent in both biofilm cells and in planktonic cells. At pH
      7.0, fluoride at concentrations < 10 mM had little or no effect. Pretreatment of
      hydroxyapatite discs with fluoride varnish (Fluor Protector) or fluoride
      solutions caused a statistically significant reduction of lactic acid formation
      in associated, growing biofilms of Strep. mutans. Fluoride varnish and 0.2% (47.6
      mM) sodium fluoride solution exhibited a statistically significant inhibitory
      effect on lactate production.

PMID- 11456350
TI  - Enhanced cyclooxygenase-2 mRNA expression in human gingival fibroblasts induced
      by cell contact with human lymphocytes.
AB  - Prostaglandins, especially prostaglandin E2 (PGE2), play a crucial role in the
      pathogenesis of periodontal disease. We have previously reported that
      inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor alpha
      (TNFalpha) increase the production of PGE2 in human gingival fibroblasts. In this
      study, we investigated the effect of cell-to-cell interactions between gingival
      fibroblasts and lymphocytes on PGE2 production by using co-culture technique.
      Cell-to-cell contact between gingival fibroblasts and lymphocytes synergistically
      enhanced the production of PGE2 in co-cultures. In contrast to lymphocytes, the
      cyclooxygenase-2 (COX-2) mRNA expression in gingival fibroblasts was strongly
      enhanced following cell contact between gingival fibroblasts and lymphocytes. The
      level of COX-1 mRNA expression, however, was not affected either in gingival
      fibroblasts or in lymphocytes by the interactions between fibroblasts and
      lymphocytes. The study demonstrates that cell contact between gingival
      fibroblasts and lymphocytes strongly stimulates PGE2 production partly due to
      enhanced COX-2 mRNA expression in gingival fibroblasts. The cell-to-cell contact
      between gingival fibroblasts and lymphocytes should be considered as an important
      regulatory aspect for the enhancement of PGE2 in periodontal disease.

PMID- 11456351
TI  - Effect of experimental diabetes on mandible growth in rats.
AB  - The aim of the present work was to assess the effects of experimental diabetes on
      mandible growth in rats. Experimental diabetes was induced in rats, aged 26 d, by
      a single dose of 100 mg/kg b.w. of Streptozotocin (STZ). Thirty-one d post STZ or
      vehicle injection, the animals were killed. Mandibles were resected to determine
      Mandibular Skeletal Units dimensions (MSU) and overall mandible growth.
      Statistical analysis of results revealed, for STZ treated animals as compared to
      the control group: 1) a decrease in b.w.; 2) an increase in food intake; 3) an
      increase in glucemia (200%); 4) normal hemoglobin, creatinine and plasma urea
      values; 5) a reduction in growth of symphyseal (9%), coronoid (16%), and alveolar
      (13%) heights, condyloid (11%), angular (8%), and base (3%) lengths, and
      condyloid width (8%). Mandibular length (4%), height (8%) and length of base (6%)
      were significantly lower in diabetic animals as compared to the control group. No
      significant differences in length of symphyseal process, alveolar length and
      height of base were found between groups. Rats on a restricted diet, resulting in
      a decreased b.w., and the control group exhibited similar mandibular dimensions.
      These data show that STZ-induced diabetes reduces mandibular growth, resulting in
      some deformity of the structure.

PMID- 11456352
TI  - Inositol hexasulphate, a casein kinase inhibitor, alters the distribution of
      dentin matrix protein 1 in cultured embryonic mouse tooth germs.
AB  - Immunohistochemical studies using a polyclonal antibody, raised against the
      recombinant form of dentin matrix protein 1 (DMP1), show that DMP1 was detected
      mainly in odontoblasts in cultured mouse embryonic tooth germs. However, in
      restricted areas, DMP1 staining was also observed in secretory ameloblasts, in
      the stratum intermedium and stellate reticulum, but only when the odontoblasts
      located in front of them were unstained. When the embryonic tooth germs were
      cultured in the presence of inositol hexasulfate, a casein kinase I and II
      inhibitor, staining of odontoblasts was weak or nil, whereas, in contrast,
      ameloblasts and enamel organ were strongly immunolabelled, suggesting an enhanced
      translocation of DMP1 after secretion to the secretory ameloblasts and/or stratum
      intermedium and stellate reticulum. Moreover, DMP1--was shown to be a good
      substrate for gelatinase A (MMP-2), but not to gelatinase B (MMP- 9). We
      hypothesized that DMP1--or the sub-fractions cleaved by the MMP--could behave as
      diffusible signaling molecule (s) rather than as a true dentin extracellular
      matrix component.

PMID- 11456353
TI  - Adhesive bonding of titanium nitride-plated stainless steel for magnetic
      attachments.
AB  - The purpose of this study was to evaluate adhesive bonding of resin to titanium
      nitride ion-plated stainless steel in order for magnetic attachments to survive
      in the oral environment. Two primers, Cesead II Opaque Primer (CPII) and Metal
      Primer II (MPII), and one bonding agent, Super-Bond C&B (SB), were used. The
      surfaces of stainless steel disks were ground and then plated with titanium
      nitride. After the primer and SB resin were applied, a self-curing resin was
      bonded to the metal surfaces. Shear bond strengths were determined after 24 h of
      water storage and after 2,000 thermocycles. Titanium nitride ion-plated stainless
      steel showed bond strength comparable to the non-plated material. After
      thermocycling, all specimens of the group no primer/no SB were debonded. The bond
      strengths of groups CPII/no SB, MPII/no SB and no primer/SB were significantly
      lower bond strengths than groups CPII/SB and MPII/SB. An appropriate combination
      of primer and bonding agent should be selected when bonding a magnetic attachment
      to the denture base.

PMID- 11456354
TI  - Molecular subtyping of Shigella flexneri 3a isolates by plasmid profile analysis
      and pulsed-field gel electrophoresis.
AB  - Twenty-two clinical isolates of Shigella flexneri 3a that were obtained from
      stool specimens from seven outbreaks of infection in northern Taiwan were
      subtyped and compared using plasmid profile analysis and pulsed-field gel
      electrophoresis (PFGE). Among 32 isolates, three distinct patterns were found by
      plasmid profile analysis and six by PFGE, with three different restriction
      enzymes, XbaI, SfiI, or NotI. Seven PFGE patterns were observed in a comparative
      analysis using a combination of these three enzymes. Isolates collected from the
      same outbreaks had the same PFGE combination patterns and were distinguishable
      from those obtained during other outbreaks. These findings suggest that PFGE may
      be the most powerful method of genotyping S. flexneri 3a in epidemiological
      studies.

PMID- 11456355
TI  - Serum interleukin-6 and tumor necrosis factor-alpha concentrations in children
      with mycoplasma pneumonia.
AB  - A prospective study was performed to assess the relationship among interleukin-6,
      tumor necrosis factor-alpha, C-reactive protein serum concentrations, and the
      severity of mycoplasma pneumonia in 49 children. Mycoplasma pneumonia was
      diagnosed by chest film and anti-Mycoplasma pneumoniae IgM antibody test. Serum
      concentrations of interleukin-6 and tumor necrosis factor-alpha were measured by
      using enzyme-linked immunosorbent assays. Interleukin-6 serum levels in
      mycoplasma pneumonia patients with fever for more than 3 days (41.98 +/- 67.46
      [SD] pg/mL) were significantly higher than those in patients with fever < or = 3
      days (10.01 +/- 11.74 pg/mL, p < 0.05). Interleukin-6 serum levels in those
      patients whose chest films revealed patchy consolidations or pleural effusion
      (58.11 +/- 92.19 pg/mL) were significantly higher than those in patients whose
      chest films revealed peribronchial interstitial infiltration (15.94 +/- 20.81
      pg/mL, p < 0.05). The mean levels of serum tumor necrosis factor-alpha were not
      statistically significant in the different duration of fever and chest film
      findings. These results suggest that interleukin-6 serum concentration, rather
      than tumor necrosis factor-alpha, may be a potential indicator of the severity
      and outcome of mycoplasma pneumonia.

PMID- 11456356
TI  - Clostridium bacteremia: emphasis on the poor prognosis in cirrhotic patients.
AB  - Bacteremic episodes caused by anaerobes are unusual and the clinical importance
      of Clostridium bacteremia remains unclear. This retrospective case study examined
      the risk factors among a group of patients who developed Clostridium bacteremia.
      Medical records from 73 episodes of clostridial bacteremia in 73 patients treated
      in a medical center during an 11-year period were reviewed. Of all episodes, 96%
      were community-acquired. Twelve percent of patients had polymicrobial bacteremia,
      with Escherichia coli being the most common accompanying bacterium. Diabetes
      mellitus (26%) and liver cirrhosis (25%) were the most common underlying
      diseases. The most common etiological organisms were Clostridium perfringens
      (77%), Clostridium bifermentans (9%), and Clostridium septicum (4%). Only one
      patient with C. septicum bacteremia had a histocytotoxic infection, which was a
      fatal gas gangrene. Univariate analysis of data from patients with monomicrobial
      Clostridium bacteremia revealed that younger age (age < 65 years), underlying
      liver cirrhosis, and presence of septic shock at initial presentation were
      associated with fatality; but only the latter two variables were independently
      associated with fatality in multivariate logistic regression analysis.
      Appropriate antimicrobial therapy for monomicrobial Clostridium bacteremia did
      not significantly affect clinical outcomes, which might suggest that Clostridium
      species in the bloodstream can be regarded as merely contaminants or transient
      bacteremia. This suggestion was not supported by the finding that seven of 13
      cirrhotic patients with monomicrobial Clostridium bacteremia died of sepsis, of
      whom six had not receive appropriate antimicrobial therapy. Therefore, the
      clinical importance of Clostridium bacteremia should be interpreted with caution
      because of its high risk of mortality in susceptible hosts, particularly
      cirrhotic patients, who do not receive appropriate therapy timely.

PMID- 11456357
TI  - Infective endocarditis with neurologic complications: 10-year experience.
AB  - The impact of neurologic complications on clinical outcomes in infective
      endocarditis was assessed. Medical records of patients with infective
      endocarditis from January 1, 1987 through September 30,1998 were analyzed.
      Patients were divided into two groups: one with neurological complications and
      the other without. The outcomes of the two groups were compared using Fisher's
      exact test. Fifty-eight patients fulfilled the definite Duke criteria. There were
      46 men and 12 women, ranging from 3 to 71 years of age with a mean of 40.6 years.
      Pathogens of infective endocarditis were documented by blood culture in 55
      (94.8%) of 58 patients as follows: 52 with gram-positive cocci, two with gram
      negative bacilli, and one with fungus. All 58 patients had initially received
      antimicrobial agents. Eight (13.8%) of the 58 patients had received surgical
      valvular replacement because of medical treatment failure. Overall, 16 (27.6%) of
      58 patients died. Neurologic complications were either the chief complaint or one
      of the major presenting symptoms in 16 (27.6%) of the 58 patients. Patients with
      neurologic complications had a higher mortality rate (50% vs 20.9%, p = 0.025)
      than those without neurologic complications. The adjusted risk ratio for
      neurologic complications for a fatal event was 3.51 (95% CI = 1.1-11.18, p =
      0.03). Neurologic complications pose a significant problem in infective
      endocarditis. To reduce mortality, we recommend that more attention be paid to
      the treatment and prevention of the neurologic complications of infective
      endocarditis.

PMID- 11456358
TI  - Clinical characteristics of emphysematous pyelonephritis.
AB  - A total of 21 patients (20 women and one man) with emphysematous pyelonephritis
      (EPN), treated in the Kaohsiung Veterans General Hospital during the period from
      1991 through 1999 were included in this study. All of the patients were diabetic.
      The most common symptoms or signs were fever/chills (80%) and costovertebral
      angle knocking pain (71%). Diagnosis was confirmed by the presence of gas in the
      parenchyma or paranephric space on plain X-ray of the abdomen or computed
      tomography. The left kidney (11 cases, 52%) was more frequently affected than the
      right one (nine cases, 43%), and both kidneys were involved in one case.
      Obstruction of the corresponding renoureteral unit was found in 19% of the
      patients, and renal or ureteral stone was found in 23% of the patients. One third
      of the patients had type I EPN, and two-thirds had type II EPN. Escherichia coli
      was the most commonly isolated organism, accounting for 61%, 76%, and 47% of
      isolates from blood, urine, and aspirated pus culture respectively. Prompt
      control of blood sugar was begun and intravenous antibiotics were given. Drainage
      was performed in 71% of the patients, and two persons required nephrectomy
      because of poor control of the infection or complications. Overall survival was
      72%. Emphysematous pyelonephritis is a rare, life-threatening, suppurative
      infection of the renal parenchyma and perirenaL tissues. For successful
      management of EPN, appropriate medical treatment should be initiated, and
      immediate nephrectomy or drainage should not be delayed.

PMID- 11456359
TI  - Efficacy of cefepime versus ceftazidime in the treatment of adult pneumonia.
AB  - Effective empiric treatment of pneumonia requires antibiotic coverage against
      gram-negative and gram-positive pathogens, including drug-resistant isolates.
      This study evaluated the efficacy of cefepime treatment in 20 patients with
      community-acquired pneumonia (CAP) and 21 patients with hospital-acquired
      pneumonia (HAP), and ceftazidime treatment in 20 patients with HAP. The mean age
      of patients was over 70 years. More than half of the patients had multiple lobe
      involvement. There was no significant difference in the severity of illness
      according to the acute physiology, age, chronic health evaluation (APACHE) III
      score between the HAP-cefepime and HAP-ceftazidime group. The most common
      bacteria isolated from sputum of patients with CAP were Streptococcus pneumoniae
      (n = 7), Klebsiella pneumoniae (n = 4), and Pseudomonas aeruginosa (n = 2). In
      patients with HAP, P. aeruginosa (n = 13), Acinetobacter baumannii (n = 11),
      Serratia marcescens (n = 6), K. pneumoniae (n = 5), Stenotrophomonas maltophilia
      (n = 5), Enterobacter cloacae (n = 3), Citrobacter spp. (n = 2), and Escherichia
      coli (n = 2) were isolated. The cure rates were 95%, 76%, and 60% in the CAP
      cefepime group, the HAP-cefepime group, and the HAP-ceftazidime group,
      respectively. The increased rates of antimicrobial resistance commonly found
      among isolates causing CAP and HAP indicate that extended-spectrum antimicrobial
      agents, such as cefepime, would be more appropriate therapeutic agents.

PMID- 11456360
TI  - Comparative study of the efficacy and safety of valaciclovir versus acyclovir in
      the treatment of herpes zoster.
AB  - Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae
      family, has well-documented efficacy and tolerability in the treatment of herpes
      zoster. Its limited oral bioavailability and short half-life, however,
      necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could
      be rapidly converted to acyclovir after oral administration, resulting in a three
      to five-fold increase in acyclovir bioavailability compared with oral acyclovir
      in humans. Valaciclovir allows less frequent dosing and maintains the safety
      profiles of the parent drug. During the period from October 1996 through May
      1998, a randomized, prospective study was performed in the Kaohsiung Veterans
      General Hospital to compare the safety and efficacy of valaciclovir with
      acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients
      presenting with herpes zoster within 72 h after the onset of rash were enrolled
      and randomized to receive one of the following treatments: 1000 mg valaciclovir
      three times daily for 7 days or acyclovir 800 mg five times daily for 7 days.
      Patients were followed up for 29 days beginning with the start of therapy. A
      total of 57 patients were enrolled and randomized to receive valaciclovir (n =
      32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in
      the acyclovir group did not complete the study. The intent-to-treat analysis (57
      patients) showed that valaciclovir significantly accelerated the resolution of
      herpes zoster-associated pain compared with acyclovir; on day 29, the
      valaciclovir group was 23% superior to the acyclovir group. There was no
      clinically significant difference in the nature, frequency or severity of adverse
      events between these two groups, although one and three adverse events were
      reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude
      that in the management of herpes zoster, valaciclovir accelerates the resolution
      of pain and offers a simpler dosing, and maintains the favorable safety profile
      of acyclovir.

PMID- 11456361
TI  - Acute lupus pneumonitis mimicking pulmonary tuberculosis: a case report.
AB  - We report a case of systemic lupus erythematosus in a 15-year-old girl with
      initial presentation as acute lupus pneumonitis. A fulminant course with
      pancytopenia and respiratory distress were developed 3 weeks after symptom onset.
      Chest radiographs revealed an interstitial pattern with miliary nodules over
      bilateral lower lung fields that mimics miliary tuberculosis. The patient was
      treated with intravenous immunoglobulin and antituberculosis drugs because the
      infection-associated hemophagocytic syndrome and pulmonary tuberculosis could not
      be excluded from the clinical course. The response to antituberculosis treatment,
      however, was poor and her respiratory condition deteriorated rapidly to impending
      respiratory failure 1 week after admission. Systemic lupus erythematosus with
      acute lupus pneumonitis was then diagnosed based on the fulminant clinical course
      and accordant laboratory results. Corticosteroid (methylprednisolone) and
      cytotoxic agent (cyclophosphamide) pulse therapies were applied twice and once,
      respectively. She recovered gradually after receiving the immunotherapy.

PMID- 11456362
TI  - Epstein-Barr virus-associated hemophagocytic syndrome masquerading as lymphoma: a
      case report.
AB  - Virus-associated hemophagocytic syndrome (VAHS) is a non-neoplastic, generalized
      histiocytic proliferation with prominent hemophagocytosis associated with a
      systemic viral infection. Although Epstein-Barr virus (EBV) is one candidate
      virus for this association, thorough serologic and molecular biologic studies to
      determine the presence of the viral infection have been lacking in many reports.
      Whereas elevated liver function tests are common findings in patients with VAHS,
      exudative ascites and abdominal lymphadenopathy are rare. We describe a case of
      EBV-AHS masquerading as lymphoma in which treatment with intravenous
      immunoglobulins was associated with complete clinical remission at 2 years and 6
      months after the onset. Regardless of the exact mechanism responsible for ascites
      formation in VAHS, this case adds support to the possible involvement of EBV in
      patients with abdominal lymphadenopathy and ascites.

PMID- 11456363
TI  - Steroid allergy: report of two cases.
AB  - Corticosteroid preparations have anti-inflammatory and immunosuppressive
      properties and are widely used in the treatment of asthma and allergic disorders.
      Steroids themselves, however, can induce hypersensitivity reactions. The number
      of reports on contact allergy or anaphylactic reactions is increasing. Steroid
      hypersensitivity should be considered in any patient whose dermatitis becomes
      worse with topical steroid therapy, or in patients who develop systemic allergic
      reactions after the use of systemic steroids. The diagnosis can be confirmed by
      skin testing, in vitro evidence of specific IgE, oral or parenteral challenge, or
      an allergic patch test. The latter may be positive within 20 min, which indicates
      immediate contact urticaria, or at 72 to 96 h, which indicates delayed contact
      hypersensitivity. In this article we report two cases of steroid allergy. Case 1
      was a 5-year-old asthmatic boy with an anaphylactic reaction to steroids and
      aspirin. Case 2 was a 2-year-old boy with atopic dermatitis and steroid contact
      urticaria. Both cases 1 and 2 showed positive results to triamcinolone,
      dexamethasone, hydrocortisone, and methylprednisolone in the immediate skin
      allergy test. Case 2 had immediate contact urticaria to hydrocortisone and
      clobetasone butyrate. Case 1 had a positive systemic allergic reaction to
      cortisone acetate, prednisolone, and dexamethasone on the oral steroid challenge
      test, and also had aspirin induced angioedema and urticaria 10 min after
      challenge with 50 mg aspirin.

PMID- 11456364
TI  - Mechanisms of antifungal agent resistance.
AB  - During the past decade, yeast infections have had an important role in nosocomial
      infections due to alterations in the immune status of patients. Coincidentally
      with the increased usage of antifungal agents, the number of reports of drug
      resistance has increased, which highlights the need for understanding the
      molecular mechanisms of antifungal agent resistance. This review describes the
      mechanisms of action of antifungal agents, cellular factors contributing to drug
      resistance, the known molecular mechanisms of drug resistance, and proposed but
      unproved molecular mechanisms of drug resistance. This review also proposes
      possible strategies for preventing drug resistance.

PMID- 11456365
TI  - Human papillomavirus type 18 in colorectal cancer.
AB  - Human papillomaviruses (HPVs) have been recognized as the etiological agent of
      warts, and they may also be associated with many cancers. HPV-18 is very common
      both in genital papillomas and in large bowel cancer. The relation between HPV-18
      infection and natural course of colorectal cancer has not been fully defined. In
      this study, normal mucosa and colorectal cancer tissue were evaluated for the
      presence of HPV gene to determine whether or not HPV was involved in the
      development of colon neoplasm. The DNA extracted from colon tissue was screened
      for HPV by polymerase chain reaction (PCR) to amplify the viral gene fragment.
      These PCR products were digested with restriction enzyme, and Southern blotting
      was then performed to confirm the existence of HPV-18. The nucleotide sequence
      related to HPV-18 DNA was detected in 53% (10/19) of the normal mucosa specimens
      and in 84% (16/19) of the colorectal cancer specimens. The correlation between
      cancer samples and positive rate of HPV-PCR was statistically significant by chi
      square test (p < 0.01). These data indicate that HPV-18 can infect the normal
      mucosa of the colon, and that this infection may be a risk factor for the
      development of colorectal cancer. The presence of HPV-18 DNA in patients with
      colorectal cancer suggests that the pathogenesis of colorectal cancer includes
      viral involvement.

PMID- 11456366
TI  - Effectiveness of a positive expiratory pressure device in conjunction with beta2
      agonist nebulization therapy for bronchial asthma.
AB  - Patients with asthma often show increased airway hyperreactivity and mucus
      hypersecretion. Although beta2-agonist therapy is one of the most common and
      effective ways used to relieve airway obstruction, the use of a positive
      expiratory pressure device (PEPD) is also effective in mucus clearance. However,
      no previously reported study has examined the effectiveness of these two
      therapies used in combination. This study assessed the effectiveness of a PEPD on
      beta2-agonist nebulization therapy by measuring the pulmonary function before and
      after nebulization therapy in 54 asthmatic patients. The results show that the
      use of PEPD after beta2-agonist nebulization therapy improved pulmonary function
      compared with the use of beta2-agonist nebulization therapy alone, as shown by
      the increases in forced midexpiratory flow and forced vital capacity (FVC).
      Patients with forced expiratory volume in 1 sec (FEV1) below 85% FVC obtained a
      significant improvement in FEV1 and FVC after using PEPD. When PEPD was used
      before beta2-agonist nebulization therapy, there were no obvious direct
      bronchodilative effects. The use of PEPD after beta2-agonist therapy, however,
      significantly enhanced the bronchodilative effect of beta2-agonist therapy in
      patients with an FEV1 below 85% FVC. The additional effect of PEPD use in
      improving pulmonary function after beta2-agonist nebulization therapy might be a
      result of an enhancement in mucus clearance.

PMID- 11456367
TI  - The use of antibiotics critical to human medicine in food-producing animals in
      Taiwan.
AB  - There are increasing public health concerns about antibiotics used in food
      producing animals that may contribute to the development of resistance in human
      pathogens. Such resistance may be critical to human medicine when resistance
      develops to drugs that treat certain pathogens of which there is no good
      alternative therapy. We surveyed 10 farms, eight feed mills, and one animal drug
      distributor in Taiwan to determine the major antibiotics used in food-producing
      animals, and the extent of use of five drugs that may select for resistance to
      antibiotics that are critical for human medicine. The five animal drugs, and the
      resistance of human drug/class they may select for, included avoparcin
      (vancomycin/glycopeptides), avilomycin (ziracin/envirninomycins), enrofloxacin
      (ciprofloxacin/fluoroquinolones), virginiamycin (quinupristin and dalfopristin
      combination/streptogramins), and kanamycin (gentamicin/aminoglycosides).
      Tetracyclines were the class of antibiotic that was most widely used in the
      greatest amounts. Over the past 12 months, the number of farms, chicken feed
      mills, and pig feed mills, that have respectively reported the use of avoparcin
      was 1 (10%), 5 (63%), 0; avilomycin 0, 0, 3 (50%); enrofloxacin 4 (40%), 1 (13%),
      3 (50%); virginiamycin 2 (20%), 5 (63%), 0; and kanamycin 3 (30%), 1 (13%), 1
      (17%). We conclude that although the most commonly used antibiotics (ie
      tetracyclines) have little effect on human medicine, there is a widespread use of
      antibiotics that may select for critical forms of resistance in human pathogens
      in food-producing animals.

PMID- 11456368
TI  - Radionuclide therapy for painful bone metastases. An Italian multicentre
      observational study. Writing Committee of an Ad Hoc Study Group.
AB  - BACKGROUND: It has been affirmed that observational studies give analogous
      results to randomised controlled ones. METHODS: A multicentre observational trial
      was conducted between 1996-1998 in order to evaluate the efficacy of palliative
      radionuclide therapy for bone metastases in a large number of patients. An
      evaluation was made on 510 patients with prostate cancer and painful bone
      metastases, treated with a single iv. dose of 89Sr-chloride (527 treatments) or
      186Re-HEDP (83 treatments), in 29 Italian Nuclear Medicine Departments. Eighty
      one patients received up to five injections, totalling 100 retreatments. Patients
      were followed up for a period of 3 months-2 years. Results were expressed at four
      levels of response: excellent, good, mild, and nil. RESULTS: Responses were
      excellent in 26.4%, good in 33.3%, mild in 21.3% and nil in 19% of all
      treatments, while good and excellent responses were obtained in 48% of
      retreatments. No statistically significant correlations were found between
      response and age of patients, skeletal extension of tumour, pretherapeutic PSA
      levels, evidence of non-bony metastases, previous chemotherapy and/or external
      beam radiotherapy; osteolytic lesions responded worse than osteoblastic or mixed
      ones. Hematological toxicity (mild to moderate), mainly affecting platelets, was
      observed in 25.5% of all treatments and in 38.9% of retreatments. No clear
      differences were found between the two radiopharmaceuticals employed.
      CONCLUSIONS: Bearing in mind that observational studies can provide just as
      accurate results as randomised controlled trials, this study confirms the main
      findings of various limited monocentre trials.

PMID- 11456369
TI  - Perfusion and functional abnormalities outside the septal region in patients with
      left bundle branch block assessed with gated SPECT.
AB  - BACKGROUND: The presence of a left bundle branch block (LBBB) pattern on the
      electrocardiogram may frequently lead to perfusion defects in the septum not
      necessarily due to ischemic heart disease, but probably due to abnormal septal
      wall motion. The introduction of gated single photon emission computed tomography
      (SPECT) allows the evaluation of myocardial perfusion and function in one study.
      Accordingly, we analysed perfusion and function and the relation between
      perfusion and regional function in the septal region in patients with a LBBB
      without evidence of a previously sustained myocardial infarction. METHODS: We
      selected 37 patients with a LBBB without a history of a previous myocardial
      infarction, which was confirmed by echocardiography and/or coronary angiography.
      All patients underwent technetium-99m tetrofosmin gated SPECT myocardial imaging.
      Twelve control patients with a low likelihood of coronary artery disease and a
      normal technetium-99m tetrofosmin gated SPECT myocardial perfusion scintigram
      were selected as a reference population. The left ventricle (LV) was divided into
      18 segments, which were scored for perfusion and function (wall motion and wall
      thickening) on a 4-point scale. RESULTS: The average LV end-diastolic volume was
      higher and the average LV ejection fraction was lower in patients with LBBB as
      compared to controls (142+/-90 vs. 81+/-18 ml, and 48+/-19 vs 62+/-7%, p=0.03 and
      p=0.02, respectively). Not only in the septum, but also in the other segments,
      reduced myocardial perfusion and abnormal wall motion/wall thickening was
      observed in the patients with LBBB (p<0.0001 vs controls). Patients with LBBB
      showed no correlation between perfusion and function in the septum, and between
      perfusion in septum and global LV function (r=0.21, p=0.2; r=0.10, p=0.6,
      respectively). Conversely, a good correlation was found between perfusion and
      function, either regional or global, in the remote segments (both r=0.79,
      p<0.0001). CONCLUSIONS: We conclude that patients with LBBB without a previous
      myocardial infarction show cardiomyopathic changes with perfusion and wall motion
      abnormalities, involving the entire left ventricle. The severity of diminished
      septal perfusion is not directly associated with the severity of septal wall
      motion abnormalities or global LV function. However, in the myocardial segments
      remote from the septum, reduced perfusion is closely associated with functional
      abnormalities.

PMID- 11456370
TI  - Evaluation of the 2nd generation radio-receptional assay for anti-TSH receptor
      antibodies (TRAb) in autoimmune thyroid diseases. Comparison with 1st generation
      and anti-thyroperoxidase antibodies (AbTPO).
AB  - BACKGROUND: The detection of autoantibodies to the TSH-receptor (TRAb) by radio
      receptor assays (RRA) is widely requested in clinical practice for the diagnostic
      workup of Graves' disease and its differentiation from diffuse thyroid autonomy.
      Additionally, TRAb measurement can be useful during antithyroid drug treatment of
      Graves' disease to evaluate the risk of relapse after therapy discontinuation.
      Nevertheless, some patients affected by Graves' disease are TRAb-negative when
      1st generation assay is used. METHODS: In this study we evaluated the diagnostic
      performance of a newly developed 2nd generation TRAb assay (TRAK human DYNOtest,
      BRAHMS Diagnostica GmbH, Berlin, Germany) in 74 untreated patients affected by
      Graves' disease, 53 untreated patients affected by Hashimoto's thyroiditis and 88
      patients affected by euthyroid nodular goiter. We also compared the new TRAb
      assay with the 1st generation test (TRAK Assay, BRAHMS Diagnostica GmbH, Berlin,
      Germany) and anti-thyroperoxidase assay (AbTPO DYNOtest, BRAHMS Diagnostica GmbH,
      Berlin). RESULTS: The 2nd generation TRAb assay showed the better diagnostic
      sensitivity in Graves' disease (97%) with respect to the 1st generation assay
      (85%) and AbTPO assay (64%). The AbTPO assay was positive in 50 of 53 (94%)
      patients affected by autoimmune thyroiditis. The 1st and 2nd generation TRAb
      assays were positive in 4 (7%) and 7 (13%) of 53 patients affected by autoimmune
      thyroiditis, respectively. No patients affected by nodular goiter showed positive
      1st and 2nd generation TRAb assay while AbTPO levels were positive in 8 of 88
      patients (specificity 91%). CONCLUSIONS: In conclusion, the 2nd generation TRAb
      assay is clearly more sensitive than the 1st generation test and should be used
      in clinical practice to minimize the incidence of TRAb-negative Graves' disease.
      Long term prospective studies are needed to evaluate the prognostic role of 2nd
      generation TRAb assay in Graves' disease. The assay of AbTPO is the best marker
      for autoimmune thyroiditis but is clearly less sensitive than 1st and 2nd
      generation TRAb assays in Graves' disease. Consequently, AbTPO assay should not
      be performed in Graves' disease neither alone or in association with TRAb.

PMID- 11456371
TI  - Radiopharmaceuticals for bone lesions. Imaging and therapy in clinical practice.
AB  - Bone scintigraphy continues to be one of the most commonly performed procedures
      in nuclear medicine. The radionuclide bone scan remains an excellent modality to
      detect metastatic disease in patients suffering from primary malignancies. This
      article reviews a number of aspects of bone scintigraphy such as bone physiology,
      radiopharmaceuticals and uptake mechanisms. As 99mTc labelled bis(di)phosphonates
      are the most frequently used this article is centred around these imaging agents.
      In addition to diagnostic bone scintigraphy the use of various bone seeking
      agents has been extended to the palliative treatment of bone metastases. In this
      context the radiobiological characteristics of various radionuclides as 89Sr,
      32p, 153Sm, 186Re and 117Sn is elucidated. In addition, the clinical efficacy for
      pain killing of these radionuclides is elucidated on the basis of the radiation
      properties of these agents. It is concluded that 89Sr and 186Re are presently the
      radionuclides of choice. The latter agent has a slight advantage as its imaging
      photons enable individual dosimetry, resulting in an optimosed application
      scheme.

PMID- 11456372
TI  - Physiopathological basis of bone turnover.
AB  - Bone remodeling involves the continuous removal of bone (bone resorption)
      followed by synthesis of new bone matrix and subsequent mineralization (bone
      formation). The principal cells that mediate the boneforming processes of the
      skeleton are osteoblast cells. They are responsible for the production of the
      matrix constituents and the differentiation of osteoblasts from stromal cell
      precursors is stimulated by several hormonal and non-hormonal molecules. On the
      other hand, the osteoclasts are giant multinucleated cells responsible of bone
      resorption. They are formed in the bone marrow and mature cells are stimulated by
      PTH and locally acting agents such as transforming growth factor alpha
      (TGFalpha), tumor necrosis factor (TNF) interleukin 1 (IL-1) and interleukin 6
      (IL-6). The first events during bone remodeling is osteoclast activation,
      followed by osteoclast formation, polarization constitution of the ruffled
      border, resorption and ultimately apoptosis. Osteoclast apoptosis is followed by
      a series of sequential changes in cells in the osteoblast lineage, including
      osteoblast chemotaxis, proliferation and differentiation, which in turn is
      followed by formation of mineralized bone and cessation of osteoblast activity.
      The final phase of the formation process is cessation of osteoblast activity. The
      resorption lacunae are usually repaired either completely or almost completely.
      Understanding the sequence of cellular events may be important to better know the
      mechanisms responsible for bone loss that occurs in age and in several
      pathological conditions.

PMID- 11456373
TI  - Bone scintigraphy and the added value of SPECT (single photon emission
      tomography) in detecting skeletal lesions.
AB  - Skeletal metastases are one of the major clinical problems for the oncologist.
      Over the last several decades bone scintigraphy has been used extensively in
      detecting bone involvement since it can provide information about disease
      location, prognosis and the effectiveness of treatment. Bone scan offers the
      advantage of total body examination, and images bone lesions earlier than other
      techniques. In this paper the main clinical problems related to the most common
      applications of bone scan in breast, prostate, lung cancer and other tumours are
      discussed. The experience carried out at the National Cancer Institute of Milan
      by using bone SPECT to detect single bone metastases is reported. One hundred and
      eighteen patients with bone metastases (from different tumour types: breast,
      lung, prostate, lymphomas, etc.) were studied by planar scintigraphy, SPECT and
      other radiological modalities (CT, MRI or X-rays). The overall performances of
      bone SPECT were sensitivity: 90.5% (19/21), specificity 92.8% (90/97), positive
      predictive value 73% (19/26), negative predictive value 97.8% (90/92), accuracy
      92.4% (109/118). Considering breast cancer, the most frequent pathology in our
      series, and the lumbar spinal tract, the most common skeletal segment involved,
      the figures of merit of SPECT were: sensitivity 100% (4/4), specificity 95.3%
      (41/43), positive predictive value 66.7% (4/6), negative predictive value 100%
      (41/41), accuracy 95.7% (45/47). In conclusion bone SPECT showed very good
      performances, in particular improving the predictive value of planar scan in the
      diagnosis of vertebral metastases.

PMID- 11456374
TI  - Radio-guided surgical biopsy for the diagnosis of suspected osseous metastases.
AB  - Radioisotope bone scanning is frequently employed in staging malignancies.
      However, false positive results are common, and biopsy is usually required. In
      the absence of plain radiographic abnormalities or local symptoms, localization
      of the area of abnormal tracer activity at the time of open rib or sternum biopsy
      may be difficult. It often requires resection of a large portion of one or more
      ribs or other bones to assure that the target area was biopsied, and still the
      area in question is commonly missed. In this setting, the newly-developed, small
      gamma probe is now used as a tool to allow precise intraoperative localization of
      increased tracer activity in the target bone. The use of gamma counting is an
      easy, highly accurate aid (100% sensitivity) to localize areas of abnormal
      radioisotope uptake in suspected asymptomatic osseous metastases, usually for
      open biopsy of a rib. The use of this technique obviates the need to obtain
      intraoperative localizing radiographs to confirm accurate rib identification,
      thereby substantially decreasing operative time.

PMID- 11456375
TI  - Detection of bone metastases in cancer patients by 18F-fluoride and 18F
      fluorodeoxyglucose positron emission tomography.
AB  - The use of positron emission tomography (PET) in clinical oncology continues to
      increase and although there is now a large literature on the use of PET with
      various tracers in a wide variety of cancers, there has previously been
      relatively little use specifically in the evaluation of skeletal metastases.
      However, a number of reports on PET in this area of oncology are now becoming
      available. The potential advantages of PET over conventional nuclear medicine
      techniques, including improved spatial resolution, absolute quantitation and the
      acquisition of tomographic studies as a routine, are also of potential benefit in
      this area. The bone agent, 18F-fluoride and the tumour agent 18F
      fluorodeoxyglucose, have been used to evaluate both benign and malignant skeletal
      disorders qualitatively and quantitatively and the current knowledge with respect
      to the skeleton in cancer patients is summarised in this article.

PMID- 11456376
TI  - Radiological imaging for the diagnosis of bone metastases.
AB  - Primary neoplasms of the skeleton are rare, but metastatic involvement is,
      unfortunately, a common occurrence. This is particularly true for certain primary
      tumors. Skeletal metastases are clinically significant because of associated
      symptoms, complications such as pathological fracture and their profound
      significance for staging, treatment and prognosis. Detection of bone metastases
      is, thus, an important part of treatment planning. The frequency with which
      metastases are detected varies considerably with the type of primary tumor and
      with the methodology utilized for detection. Four main modalities are utilized
      clinically: plain film radiography, CT scan, nuclear imaging and magnetic
      resonance imaging. In this discussion, we will review literature on the radiology
      of skeletal metastases with respect to lesion detection, assessment of response
      to treatment and possible therapeutic implications. The bulk of the discussion
      will focus on MRI and nuclear studies since most of the recent advances have been
      made in these areas.

PMID- 11456377
TI  - Pathogenesis and pharmacological treatment of bone pain in skeletal metastases.
AB  - Sixty-five percent of patients with advanced cancer present bone metastases and
      most of them present a rather slow clinical course characterized by pain,
      mobility deficiencies and skeletal complications such as fractures and spinal
      cord compression. Metastatic involvement of the bone is one of the most frequent
      causes of pain in cancer patients and represents one of the first signs of
      widespread neoplastic disease. The pain may originate directly from the bone,
      from nerve root compression or from muscle spasms in the area of the lesions. The
      mechanism of metastatic bone pain is mainly somatic (nociceptive) even though, in
      some cases, neuropathic and visceral stimulations may overlap. The conventional
      symptomatic treatment of metastatic bone pain requires the use of
      multidisciplinary therapies such as radiotherapy in association with systemic
      treatment (hormonotherapy, chemotherapy, radioisotopes) with the support of
      analgesic therapy. Recently, studies have indicated the use of bisphosphonates in
      the treatment of pain and in the prevention of skeletal complications in patients
      with metastatic bone disease. In some patients pharmacological treatment,
      radiotherapy, radioisotopes administered alone or in association are not able to
      manage pain adequately. The role of neuroinvasive techniques in treating
      metastatic bone pain is debated. The clinical conditions of the patient, his life
      expectancy and quality of life must guide the physician in the choice of the best
      possible therapy.

PMID- 11456378
TI  - Clinical utility of biochemical marker of bone remodelling in patients with bone
      metastases of solid tumors.
AB  - Bone turnover is characterized both by the formation of new bone by the
      osteoblasts and the resorption of old tissue by the osteoclast. This process
      takes place only on the surface of bone and can be described in terms of spatio
      temporal events that are the bone metabolic unit and the bone remodelling cycle.
      The former consists of a discrete group of cells (osteoblasts and osteoclasts)
      involved in a particular remodelling event while the latter represents the
      succession of resorption and formation. In a typical remodelling cycle,
      resorption takes 7-10 days, whereas formation requires 2-3 months. Remodelling is
      regulated either by local or systemic factors, including electrical and
      mechanical forces, hormones (e.g. parathyroid hormone, sexual steroids,
      calcitriol, cortisol, thyroid hormones, calcitonin), growth factors and
      cytokines. Recently different circulating biochemical markers have been proposed
      for the investigation of bone turnover. In addition to classical parameters such
      as serum alkaline phosphatase and urinary calcium and hydroxyproline, new markers
      have gained clinical attention because of their accuracy in assessing the dynamic
      changes in bone remodelling (bone alkaline phosphatase, osteocalcin, propeptides
      PICP and PINP, tartrate-resistant acid phosphatase, deoxypyridinoline,
      pyridinoline, telopeptide CTx and NTx). The aim of this review is to present the
      recent advances in this field and the clinical application of markers of bone
      turnover in patients with bone metastases from solid tumors. Also the cellular
      and molecular bases of bone remodelling are reported with details.

PMID- 11456379
TI  - Bone pain palliation with strontium-89 in cancer patients with bone metastases.
AB  - Strontium-89 is a pure beta-emitting radioisotope, a chemical analogue of
      calcium, and it is therefore avidly concentrated by areas of high osteoblastic
      activity. Selective uptake and prolonged retention at sites of increased bone
      mineral turnover provide precise bone lesions targeting. 89Sr chloride
      (commercialised as Metastron) is typically administered in a single 150 MBq
      parenteral dose. Its radioactive emission poses very little radioprotection
      concerns. Overall, studies show pain relief in up to 80% of patients, of which 10
      to 40% became effectively pain free. The mean duration of palliation was 3-4
      months. The mechanism of pain relief is controversial ; it is probably, but not
      only, related to the absorbed dose in the tumour and bone. There is no clear dose
      response relationship. The only reported toxicity is temporary myelosuppression.
      WBC and platelets should be monitored at least on a weekly basis until they
      return to baseline. It seems that only patients with a reasonably good general
      condition stand to benefit from this treatment. In conclusion, systemic
      radionuclide therapy using 89Sr represents a feasible, safe, effective, well
      tolerated and cost-effective palliative treatment in patients with refractory
      bone pain.

PMID- 11456380
TI  - 186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone
      metastases.
AB  - Pain palliation with bone-seeking radiopharmaceuticals is an effective treatment
      modality in patients with advanced metastatic bone cancer. Several studies have
      shown encouraging clinical results of palliative therapy using 186Re-HEDP, with
      an overall reported response rate of +/-71% for painful osseous metastasized
      prostate and breast cancer patients. 186Re-HEDP is a very potential isotope with
      numerous advantageous characteristics for this purpose. Myelosuppressive toxicity
      is limited and reversible, which makes repetitive treatment safe. However,
      individual studies are difficult to compare, and are hampered by the numerous and
      different methods used to assess clinical response. Standardized clinical
      response assessment using the objective multi-dimensional pain evaluation model
      should therefore be implemented.

PMID- 11456381
TI  - Systemic metabolic radiotherapy with samarium-153 EDTMP for the treatment of
      painful bone metastasis.
AB  - Various radioisotopes conjugated to pyrophosphate analogues have been developed
      for systemic metabolic radiotherapy. Samarium-153-EDTMP is a 1:1 complex of
      radioactive Samarium-153 and a Tetraphosphonate [ethylenediamine-tetramethylene
      phosphonic acid (EDTMP)]. Samarium Sm-153-EDTMP has a high affinity for skeletal
      tissue and concentrates by chemiabsorption in areas of enhanced metabolic
      activity, where it associates with the hydroxyapatite crystal. Samarium-153
      Lexidronam [Quadramet (R)] has been approved for routine use by the FDA. This
      agent offers several advantages over other agents used for palliating bone pain.
      Due to its half-life of 46 hours and its beta emissions, a high dose rate can be
      delivered to regions adjacent to enhanced osteoblastic activity over a short
      period of time with little residual long term activity being left in the bone
      marrow. This paper summarizes both animal studies and clinical studies performed
      with this agent. Special emphasis will be given to the pivotal Phase-III clinical
      studies and subsequent studies performed since its approval by the FDA. Special
      considerations regarding appropriate selection of patients, preparation, follow
      up of patients and adjustments to the usual recommended dose [1 mCi/kg (35
      Mbq/kg)] will be discussed. Current and future treatment options utilizing Sm-153
      EDTMP with other pharmaceuticals appear promising and will substantially extend
      its use into new areas. In addition, because it also emits a 103 keV gamma ray
      which makes it suitable for imaging and assessment of biodistribution, dosimetric
      applications are possible in the future.

PMID- 11456382
TI  - Asthma, disease management, and research: attempting to unravel a Gordian knot.

PMID- 11456383
TI  - A review of cough in children.
AB  - Cough is a very common symptom of respiratory disease and reason for parents to
      seek medical attention. The article presents broad clinical guidelines on the
      approach to childhood cough and discusses current controversies of the management
      of cough in children.

PMID- 11456384
TI  - The role of n-6 polyunsaturated fat in stable asthmatics.
AB  - We investigated in a clinical setting whether increased intake of linoleic acid
      alters respiratory function in 26 mild asthmatics. Subjects completed a 16-week
      dietary intervention comprising 8 weeks eating an enriched n-6 polyunsaturated
      fat diet (9.2% energy from linoleic acid) and consuming either a high
      monounsaturated or saturated fat diet in a random cross-over resign for 8 weeks.
      Neither FEV1 nor PC20 values changed significantly after increased linoleic acid
      consumption when compared with the other diets. Increased consumption of linoleic
      acid caused a 20% rise (p < or = 0.01) in plasma linoleic acid, a 38% decrease (p
      < or = 0.01) in plasma eicosapentaenoic acid, but no change in arachidonic acid.
      There were no changes in symptom scores or bronchodilator use.

PMID- 11456385
TI  - Two-year results from the asthma self-management program: long-term impact on
      health care services, costs, functional status, and productivity.
AB  - Participants in a variety of health plans, clinics and employer groups were
      invited to participate in the Asthma Self-Management Program (ASMP), an education
      program designed to improve self-management skills and daily functioning in
      individuals with asthma. The ASMP is an 8-week classroom program that provides
      information on the respiratory system, trigger avoidance, use of monitoring
      techniques and asthma medications. After program completion, graduates were
      contacted at scheduled intervals to reinforce performance of behaviors that are
      important to asthma self-management and to collect outcomes data. This paper
      reports the results of 2 years of follow-up with these individuals.

PMID- 11456386
TI  - Effects of suplatast tosilate on airway inflammation and airway
      hyperresponsiveness.
AB  - Suplatast tosilate (IPD) is a Th2 cytokine inhibitor that lowers the titer of the
      IgE antibody through specific inhibition of the production of IL (interleukin)-4
      and IL-5 by T cells and inhibits tissue infiltration by eosinophils. In this
      clinical trial, suplatast tosilate (300 mg/day) was administered orally for 4
      weeks to 25 patients (13 patients with atopic asthma, 12 patients with nonatopic
      asthma) whose bronchial asthma was staged in step 1 or step 2 according to the
      Guidelines for Prevention and Management of Bronchial Asthma, 1998. Before and
      after administration, the parameters of airway inflammation, that is, peripheral
      blood eosinophils count, serum level of eosinophil cationic protein (ECP), ECP
      level in induced sputum, airway hyperresponsiveness (Dmin), and morning peak
      expiratory flow (PEF), were measured. The peripheral blood eosinophil count,
      serum level of ECP, and ECP level in induced sputum decreased significantly. Of
      these parameters, the ECP level in induced sputum was the most sensitive.
      Furthermore, suplatast tosilate significantly inhibited Dmin. These results were
      especially significant in patients with atopic asthma. Suplatast tosilate was
      considered to have inhibited airway eosinophilic inflammation through decreases
      in peripheral blood eosinophils counts and in ECP levels in induced sputum, which
      resulted in inhibition of airway hyperresponsiveness.

PMID- 11456387
TI  - An evaluation of Open Airways for Schools: using college students as instructors.
AB  - Fifteen years ago, Open Airways for Schools (OAS) was found to be an effective
      asthma education program for elementary school children when taught by
      professionals. To determine whether OAS is effective when taught by college
      students and whether it could withstand potential cohort effects, 54 inner-city
      fourth and fifth graders were taught OAS. Paired t-tests revealed that OAS
      improved asthma knowledge, self-efficacy, self-management skills, social support,
      and perception of well-being (p < 0.05). Fifteen years later OAS continues to
      improve children's self-management skills. Facilitators with little prior
      experience who received brief training in asthma knowledge and group leadership
      skills can effectively teach OAS.

PMID- 11456388
TI  - A self-management program for adult asthma. III. Maintenance and relapse of
      skills.
AB  - Patient self-management programs have become an integral part of asthma
      treatment. The goal of such programs is to strengthen the partnership between
      patients and health care providers in controlling the condition. The present
      study analyzed how well patients maintained or relapsed in performing asthma self
      management skills over time and across settings. It was conducted by contacting
      patients who had been involved in a successful self-management program an average
      of 6 years after their participation or an average of 7 years after they
      completed training. Seventy percent of the patients agreed to participate and
      complete, either by themselves or over the telephone, a structured interview
      regarding their experiences in performing asthma self-management. On the basis of
      their responses, 53 participants were categorized into two groups: continuers or
      relapsers, according to previously developed and published criteria for relapse.
      Characteristics that distinguished the two groups were described. As anticipated,
      those classified as continuers reportedly exhibited broader repertoires of self
      management skills across an array of settings. They credited their performance
      with maintaining control over their asthma. However, two unexpected findings
      emerged in the study: First, all patients continued to use self-management skills
      to one degree or another 7 years after they had acquired these skills. Even
      patients who were categorized as relapsers regularly performed some self
      management skills, often involving self-monitoring of their breathing. Second,
      half of the patients in the relapse group reported that their asthma was in
      remission and that they were asymptomatic. The self-management skills they
      reportedly used were performed to monitor and prevent a return of asthma.

PMID- 11456389
TI  - Monitoring of peak expiratory flow rates in cork workers' occupational asthma.
AB  - Suberosis is an occupational lung disorder of cork industry workers usually
      presenting as an extrinsic allergic alveolitis, but airway involvement in some
      cases makes the diagnostic approach complex. We assessed peak expiratory flow
      rates (PEF) in 17 cork workers with asthma symptoms that worsened at work,
      comparing three methods of PEF graph analysis. Complete agreement (three
      observers) was found in 12 of 17 cases (70.6%) with the visual inspection of mean
      daily values and in 11 of 17 cases (64.7%) with the minimum, maximum, and mean
      daily values (without any consensus in two cases). According to the mean PEF
      graph, there were eight positive readings (47%), five negative readings (29%),
      and four dubious readings (24%); with the other graphic analysis, two of the
      dubious cases were reclassified as negative. When we analyzed daily variability
      >20%, we found only three positive results, one of which was in absolute
      disagreement with the visual analysis. Our results suggest that it is possible to
      demonstrate occupational asthma in cork work exposure. The visual inspection of
      PEF monitoring shows a greater number of positive results than the index of daily
      variability; however, the latter may help to sort out dubious cases.

PMID- 11456390
TI  - Health care utilization and cost in children with asthma and selected
      comorbidities.
AB  - Children with asthma use significantly more health services than other children,
      yet the majority of their health care costs are for nonasthma services. The
      objective of this study was to measure the impact of asthma and specific upper
      respiratory comorbidities on the use and cost of health care by children. A
      population-based historical cohort study from January 1, 1992 to December 31,
      1992 was conducted. Multiple visits for otitis media, sinusitis, and allergic
      rhinitis were considered comorbidities. The outcome measures were nonurgent
      outpatient care, pharmacy fills, urgent care visits, and hospital care along with
      the associated total costs. Children between ages 1 and 17 years were studied (n
      = 71,818). Children with asthma were more likely than children without asthma to
      have a comorbidity (26% vs. 9%). Children with multiple visits for otitis media,
      sinusitis, and allergic rhinitis were 1.8, 4, and 12 times more likely,
      respectively, to have a diagnosis of asthma in the same year. Children with
      asthma had a 47% probability of being in the highest total cost quintile compared
      to a 29% likelihood once adjusted for comorbidities. Visits for otitis media,
      sinusitis, and particularly allergic rhinitis appear to be overrepresented in
      children with asthma and contribute to their high utilization rate. Once a high
      risk cohort is identified, the needs of those children can be addressed through
      targeted, organized systems of care that may include guidelines or other disease
      management strategies.

PMID- 11456391
TI  - TGF-betas synthesized by RPE cells have autocrine activity on mesenchymal
      transformation and cell proliferation.
AB  - The present study investigated the effects of transforming growth factor (TGF)
      beta on retinal pigment epithelial (RPE) transformation in a simplified model and
      also whether or not TGF-beta exhibits similar proliferation effects on
      transformed RPE cells that it has on primary RPE cells. Furthermore, we examined
      the cell proliferation effects of RPE-conditioned medium (CM). A vertical wound
      measuring 2 mm in diameter was made on primary RPE monolayers. The expression of
      alpha-smooth muscle actin (SMA) by the cells located at the wound edges was
      observed using a confocal microscope under immunofluorescent staining. Cell
      proliferation was measured by incorporating 3H-thymidine into DNA. The presence
      of alpha-SMA was observed in the cells within the wound after treatment with TGF
      beta2, while negative expression was observed in control cells. TGF-betas
      inhibited the proliferation of the primary cultures of RPE cells in a dose
      dependent manner, but the spindle-shaped late-passaged RPE cells were not
      inhibited by these growth factors. The medium conditioned by RPE cells stimulated
      the proliferation of subconjunctival fibroblasts and inhibited the proliferation
      of primary RPE cells, in a manner similar to TGF-beta. These findings demonstrate
      that TGF-beta-stimulated RPE cells may evoke proliferative vitreoretinopathy
      through mesenchymal transformation and cell proliferation.

PMID- 11456392
TI  - Primary humoral immune responses to formalin inactivated hemorrhagic fever with
      renal syndrome vaccine (Hantavax): consideration of active immunization in South
      Korea.
AB  - The efficacy of a formalin-inactivated hemorrhagic fever with renal syndrome
      (HFRS) vaccine and the effectiveness of a related vaccination program have not
      been previously evaluated. We measured the primary immune responses to Hantavax
      by plaque reduction neutralizing antibody test (PRNT), hemagglutination
      inhibition test (HAI), ELISA and high density particle agglutination test (HDPA)
      in order to confirm a possible biological efficacy through independent
      substantiation of experimental results and to compare the results with previous
      studies. Following two doses of primary vaccination, the seroconversion rate of
      PRNT and HAI antibody was 33.3% (10/30) [95% C.I. 17.3-52.5%] and 26.7% (8/30)
      [95% C.I. 12.3-45.9%], respectively. The correlation between PRNT and HAI
      antibody showed a statistical significance (r=0.58, p<0.01). The seroconversion
      rate of HDPA and ELISA were both 76.7% (23/30) [95% C.I. 57.7-90.1%], which
      correlated well with each other (r=0.58, p<0.01). In our study, Hantavax elicited
      low neutralizing antibody responses, at least in the volunteers samples that we
      tested. The vaccination program, including the vaccine itself, that has been
      adopted by the national immunization program to protect against HFRS in Korea
      should be re-evaluated and re-formulated to produce a higher protective immune
      response rate.

PMID- 11456393
TI  - Granzyme B and TIA-1 expression in chronic and acute on chronic renal allograft
      rejection.
AB  - Although active inflammation may be deleterious and indicate immunologic
      activation in chronically rejected grafts, the underlying mechanism of tissue
      destruction has been little studied. Twenty-four cases of chronic rejection (CR)
      with or without acute rejection (AR) were stained with antibodies against CD3,
      CD8, CD68, granzyme B and TIA-1, and the number of positive cells were counted.
      Eleven cases of AR served as controls. The number of CD3 and CD8 positive cells
      increased in the acute on CR group compared to the CR group. About a half of CD3
      positive T cells were CD8 positive in both groups, however, the proportion of TIA
      1 or granzyme B positive cells was higher in the acute on CR group. The numbers
      of CD3, CD68, granzyme B and TIA-1 positive cells were higher in the AR group
      than the acute on CR group, however, no significant difference was found between
      the two groups. Serum creatinine level and proteinuria at the time of biopsy and
      the percentages of late onset AR and graft failure rate were higher in the acute
      on CR group than the CR group. Summarizing, these results suggest that
      infiltration of activated T cells containing cytotoxic granules plays a role in
      graft destruction in acute on CR.

PMID- 11456394
TI  - Preparation of collagen modified hyaluronan microparticles as antibiotics
      carrier.
AB  - Hyaluronan (HA), a natural glycoaminoglycan featuring an extracellular matrix,
      has been suggested as an effective biocompatible material. In this study, the
      effectiveness of HA microparticles as a carrier system for antibiotics was
      evaluated, and their physicochemical characteristics were determined.
      Microparticles were fabricated by the gelation of sulfadiazine (SD) loaded HA
      solution with calcium chloride through either a granulation (GR-microparticles)
      or encapsulation (EN-microparticles) process, and atelocollagen was incorporated
      into the microparticles as an additive in order to improve their physical
      properties. The characteristics of the microparticles were examined by scanning
      electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling
      test. In vitro release experiments were performed for 7 days and the released
      amount of SD was determined using high-performance liquid chromatography (HPLC).
      Microscopic observations revealed that the collagen incorporated HA particles had
      a more compact surface than the HA particles. DSC analysis determined a loss of
      SD crystallinity in the particles. Calcium chloride retarded the swelling of
      particles, whereas the loaded drug contents did not affect this property. Both GR
      and EN-microparticles sustained SD release with initial bursting effect. SD
      release from EN-microparticles was faster than from GR-microparticles. In
      addition, the release rate was dependent on the SD content in the microparticles.
      These results suggest that collagen modified HA microparticles have a potential
      as a release rate controlling material for crystalline drugs such as SD.

PMID- 11456395
TI  - Evaluation of gestational age based on ultrasound fetal growth measurements.
AB  - Monitoring fetal growth and assessing its predictors have important place in
      antenatal care management. Accurate prediction of gestational age (GA) and birth
      weight (BW) is clinically important. Standard growth curve chosen should be
      evaluated to see if it satisfies the criteria for a valid assesment. In this
      paper, for the purpose of contributing to develop national standards and to
      evaluate Hadlock's standard data pertaining to 1411 fetuses were examined. Of
      1411 normally growing fetuses, one measurement for AC, BPD and FL was taken by
      ultrasound. GA was assessed via menstrual history which is also confirmed by
      ultrasonography. Several variables, AC, BPD, FL, FL/AC, BPD/FL and dependent
      variables (GA & BW) were modelled mathematically. Percentile values, correlation
      coefficients were calculated and well functioning regression equations were
      produced for the fetal growth evaluation. Simple correlation model re-confirmed
      that AC, BPD and FL were well predictors of GA. Via modelling by multivariate
      regression analysis (adj. R2=937), GA=4.945 (95% CI: 4.661- 5.654) + .606 AC +
      .105 BPD + .286 FL can be estimated. It couldn't be possible establishing an
      appropriate equation for prediction of BW with current data. Our study is
      intended to draw an attention on requirement of national standards although
      Hadlock's standard growth curve may evaluate fetal development accurately.
      Forming comprehensive cohort group is under our consideration. The equation we
      developed (shown in the results), might be a working contribution.

PMID- 11456396
TI  - Calcification comparison of polymers for vascular graft.
AB  - Polytetrafluoroethylene (PTFE), polyurethane (PU) and silicone are widely known
      biocompatible polymers which are commonly used for vascular grafts. However, in
      vitro and in vivo calcifications of these polymers have been found to seriously
      compromise their quality as biomaterials. In consideration of this problem, the
      present study compared the calcification rate and extent of PTFE, PU and
      silicone. Using the in vitro flow-type method, PTFE, PU and silicone films were
      tested for 1, 4, 7, 10, 14 and 21 days. After 21 days of in vitro calcification
      test, the calcium levels on PTFE, PU and silicone were 35.89 +/- 5.01 microg/cm2,
      23.73 +/- 0.68 microg/cm2 and 19.86 +/- 5.28 microg/cm2, respectively. The higher
      observed calcium level for PTFE may be due to the effect of the rough surface of
      PTFE in accumulating calcium ions on the polymer surface. From the 7th day of
      test, the [Ca]/[P] molar ratio started to decrease over time, and PTFE showed a
      faster calcification process. This decreasing [Ca]/[P] molar ratio demonstrated
      the typical calcification mechanism consisting of phosphorus ion accumulation
      following calcium ion accumulation. This study concluded that PU and silicone are
      less calcified than PTFE film, a finding in good agreement with previously
      published studies.

PMID- 11456397
TI  - The nerve-dependency of Merkel cell proliferation in cultured human fetal
      glabrous skin.
AB  - Merkel cells are thought to function as slowly adapting mechanoreceptors and are
      known as targets for sensory nerves. However, the nerve-dependency of Merkel
      cells remains controversial. In this respect, some investigators have found
      interregional differences between hairy and glabrous skin and others have shown
      intraregional differences within denervated rat touch domes. Differences between
      species have also been reported. This study was performed to determine whether
      Merkel cells proliferate in vitro in the absence of the systemic factors, blood
      vessels and the intact nerves in human skin. Suspension organ culture was
      performed using fetal digits to investigate their in vitro proliferation. Merkel
      cells and cutaneous nerves were identified using antibodies to cytokeratin 20 and
      protein gene product 9.5 (PGP 9.5), respectively. Fetal digits of 56-82 day
      gestational age were cultured in serum free medium in a high O2 (45%)
      environment. Tissues were harvested before starting culture (D0) and 1, 4, 7, 14,
      28 d after culture. Merkel cells were observed in the volar pads and dorsal nail
      matrices at D0. After 28 d of suspension organ culture, digits looked healthy
      structurally and the number of Merkel cells had increased. However, PGP 9.5
      immunoreactive nerves were markedly diminished after 1 day of culture and almost
      disappeared after 4 days. Merkel cell proliferation in vitro suggested that
      Merkel cell development is probably nerve-independent in human fetal glabrous
      skin.

PMID- 11456398
TI  - Comparison between posterolateral fusion with pedicle screw fixation and anterior
      interbody fusion with pedicle screw fixation in adult spondylolytic
      spondylolisthesis.
AB  - There have been many reports regarding various operative methods for
      spondylolytic spondylolisthesis. However, there have been no reports regarding
      the comparison between posterolateral fusion (PLF) with pedicle screw fixation
      (PSF) and anterior lumbar interbody fusion (ALIF) with PSF. The purpose of the
      current study was to compare the clinical outcomes of PLF with PSF and ALIF with
      PSF, and to help in the selection of treatment options. Fifty-six patients with
      spondylolytic spondylolisthesis who underwent PLF with PSF (group 1, 35 patients)
      or who underwent ALIF with PSF (group 2, 21 patients) were studied. Minimum
      follow-up was 2 years. Demographic variables and disease state were similar for
      the two groups. We studied operating time, amount of blood loss, duration of
      hospital stay, clinical outcomes, complications, time at which fusion was
      complete, fusion rate, and radiological measurements. There were no significant
      differences between the two groups in terms of the amount of blood loss, duration
      of hospital stay, back pain, radiating pain, fusion rate, or complication rate.
      However, in group 2, the operation time and the time at which fusion became
      complete was longer, and in group 1 there was significant radiological reduction
      loss. In conclusion, PLF with PSF was just as effective as ALIF with PSF in terms
      of clinical outcomes, but ALIF with PSF was superior to PLF with PSF in terms of
      the prevention of reduction loss. Anterior support would be helpful for
      preventing reduction loss in cases of spondylolytic spondylolisthesis of the
      lumbar spine.

PMID- 11456399
TI  - Prevalence of antibodies to PPD and lipoarabinomannan of Mycobacterium
      tuberculosis among patients with an indication of fine needle aspiration biopsy.
AB  - Recent increase in the incidence of lung cancer often makes it difficult to
      differentiate between lung cancer and tuberculosis (TB), due to their radiologic
      similarities. Fine needle aspiration biopsy (FNAB) has been widely employed for
      the diagnosis of lung cancer and TB, but the diagnostic accuracy of TB is not
      high enough. As a rapid screening test for tuberculosis, we evaluated serological
      tests using Mycobacterium tuberculosis PPD and lipoarabinomannan (LAM) antigens.
      A total of 95 patients with indication of FNAB cytology from initial CT findings
      were enrolled. 25 patients had TB, 76 thoracic malignancy, and six (7.9%) of the
      lung cancer patients also had TB, indicating much higher prevalence of TB in
      thoracic tumor patients. Antibodies to PPD were elevated in 18 (72.0%) of 25 TB
      patients and in 22 (31.4%) of 70 patients with thoracic malignancy. In contrast,
      only 3 (4.7%) of 64 healthy controls aged 40 or above were seropositive to PPD
      antigen. The prevalence of anti-PPD antibodies in thoracic tumor patients was
      therefore significantly greater than that amongst the healthy controls (p<0.001,
      chi-square test). However, no significant difference in the prevalence of anti
      LAM antibodies was found between study subjects and controls. This study
      demonstrates that thoracic tumor patients have significantly elevated antibodies
      to PPD; therefore, high anti-PPD seroreactivity in thoracic tumor patients should
      be cautiously interpreted. A longitudinal investigation on seropositive thoracic
      tumor patients is required to determine the role of the serological test for TB
      in lung cancer patients.

PMID- 11456400
TI  - Hypoxia delays the intracellular Ca2+ clearance by Na+-Ca2+ exchanger in human
      adult cardiac myocytes.
AB  - Transient myocardial ischemia during cardiac surgery causes a loss of energy
      sources, contractile depression, and accumulation of metabolites and H+ ion
      resulting in intracellular acidosis. The reperfusion following ischemic
      cardioplegia recovers intracellular pH, activates Na+-H+ exchange and Na+-Ca2+
      exchange transports and consequently produces Ca2+ overload, which yields cell
      death. Among the various Ca2+ entry pathways, the Na+-Ca2+ exchanger is known to
      play one of the major roles during the ischemia/reperfusion of cardioplegia.
      Consequently, information on the changes in intracellular Ca2+ activities of
      human cardiac myocytes via the Na+-Ca2+ exchanger is imperative despite previous
      measurements of Ca2+ current of human single myocytes. In this study, human
      single myocytes were isolated from the cardiac tissues obtained during open-heart
      surgery and intracellular Ca2+ activity was measured with cellular imaging
      techniques employing fluorescent dyes. We report that the Na+-Ca2+ exchanger of
      adult cardiac myocytes is more susceptible to hypoxic insult than that of young
      patients.

PMID- 11456401
TI  - Interaction of TGF-beta1 and rhBMP-2 on human bone marrow stromal cells cultured
      in collagen gel matrix.
AB  - Transforming growth factor-beta1 (TGF-beta1) and bone morphogenetic protein-2
      (BMP-2) are abundant proteins in the bone matrix. However, their interaction in
      controlling osteoblast differentiation is not clearly understood. In this study,
      HBMSCs were cultured in collagen gel matrix with different condition of exogenous
      rhBMP-2 and TGF-beta1 in order to determine the interaction of BMP-2 and TGF
      beta1 on human bone marrow stromal cells (HBMSCs) differentiation. The cultured
      cells were analyzed for cell proliferation, alkaline phophatase (ALP) activity
      and mineralization staining with Von-Kossa. The cells treated with TGF-beta1
      exhibited a higher rate of cell growth than those without. However, the cells
      cultured in collagen gel matrix showed a lower rate of cell growth than the cells
      cultured in a monolayer. To investigate the effects of both cytokines on
      osteoblast differentiation, the cells were treated with 0, 1, 5, 10 ng/ml of TGF
      beta1 for 2 days. This was followed by culturing with 0, 1, 5, and 10 ng/ml of
      TGF-beta1 and 100 ng/ml of rhBMP-2 together for 3 days with the alkaline
      phosphatase (ALP) activity measured. The cells treated with 1 ng/ml of TGF-beta1
      responded efficiently to rhBMP-2 and expressed ALP activity with a level
      equivalent to that exhibited by cells that were not treated with TGF-beta1. The
      cells treated with 5 and 10 ng/ml of TGF-beta1 showed a dramatic decrease in ALP
      activity. The cells treated with 10 ng/ml of TGF-beta1 followed by rhBMP-2 alone
      exhibited an intermediate ALP activity. The cells treated with 100 ng/ml of rhBMP
      2 demonstrated Von-Kossa positive solid deposits after 3 weeks, while there were
      few Von-Kossa positive solid deposits when the cells treated with 10 ng/ml of TGF
      beta1. These results show that TGF-beta1 inhibits the effects of rhBMP-2 on the
      osteoblast differentiation of HBMSCs in a dose dependant manner. Furthermore, the
      effects of TGF-beta1 on HBMSCs are reversible. This suggest that TGF-beta1 and
      rhBMP-2 are coordinately controlled during the osteoblast differentiation of
      HMBSCs.

PMID- 11456402
TI  - A case with balanced chromosome rearrangement involving chromosomes 9, 14, and 13
      in a woman with recurrent abortion.
AB  - A phenotypically normal couple was referred for cytogenetic evaluation due to
      three consecutive first-trimester spontaneous abortions. Chromosomal analysis
      from peripheral blood was performed according to standard cytogenetic methods
      using G-banding technique. The husband's karyotype was normal. The wife's
      karyotype showed a balanced complex chromosome rearrangement (CCR) involving
      chromosomes 9, 14, and 13. There were three breakpoints: 9p21.2, 14q21, and
      13q12.2. The karyotype was designated as 46, XX, t (9;14;13)(p21.2;q21;q12.2).
      Fluorescence in situ hybridization (FISH) analysis with chromosome-specific
      libraries of chromosomes 9, 14, and 13 was performed to confirm this rare
      chromosome rearrangement. The result of FISH coincided with that obtained by
      standard cytogenetic techniques.

PMID- 11456403
TI  - Acquired pendular nystagmus with voluntary inhibition.
AB  - This report documents a case of voluntary inhibition of acquired pendular
      nystagmus after head trauma. A 30-year-old male developed oscillopsia and
      decreased visual acuity, as well as findings of acquired pendular nystagmus with
      voluntary inhibition after head trauma. The EOG finding was horizontal 18-20 Hz
      bilateral symmetrical pendular nystagmus in all directions of gaze at near and
      distant fixation. Nystagmus did not change with 14 Prism Diopter base-out prisms
      on both eyes, but it was possible to abolish it intentionally. Baclofen and
      Clonazepam had no effect in improving the patient's symptoms and EOG finding.

PMID- 11456404
TI  - A case of hemorrhagic gallbladder paraganglioma causing acute cholecystitis.
AB  - Gallbladder paraganglioma is a very rare tumor and so far only a few cases have
      been reported. Most of these were asymptomatic and were found incidentally during
      operation. Recently, we experienced a gallbladder paraganglioma that gave rise to
      hemorrhage, which in turn caused acute cholecystitis. Our case involved a 45 year
      old female patient complaining of an intermittent right upper abdominal pain.
      After a preoperative evaluation, cholecystectomy and lymphadenectomy were
      performed under the impression of gallbladder cancer with acute cholecystitis.
      Postoperative pathologic examination revealed a hemorrhagic gallbladder
      paraganglioma accompanied by acute cholecystitis. Immunohistochemical staining of
      the chief cells for neuron specific enolase, chromogranin and synaptophysin were
      positive. Sustentacular cells also stained positively for S100 protein.

PMID- 11456405
TI  - Acute eosinophilic pneumonia associated with amitriptyline in a hemodialysis
      patient.
AB  - Drugs are well known causes of eosinophilic lung disease. In many patients, drug
      induced eosinophilic lung disease presents with transient eosinophilic
      infiltrates that disappear after discontinuation of the drug. Some patients,
      however, experience a fulminant, acute eosinophilia-like disease. Recently, we
      experienced a case of amitriptyline-associated acute eosinophilic pneumonia with
      respiratory failure in a diabetic hemodialysis patient. Eight days after
      treatment with amitriptyline, sudden fever, chill, dry cough and dyspnea
      developed. Subsequently, multiple patch consolidations appeared on the chest
      radiographs. Bronchoalveolar lavage (BAL), established a diagnosis of acute
      eosinophilic pneumonia. After immediate discontinuation of amitriptyline, a rapid
      clinical and radiological improvement was observed. The present case indicates
      that the possibility of acute eosinophilic pneumonia should be fully considered
      in dialysis patients developing unexplained respiratory symptoms while on
      amitriptyline therapy.

PMID- 11456406
TI  - Extraovarian granulosa cell tumor.
AB  - A 54-year-old woman was admitted to our hospital complaining of postcoital
      bleeding. Sonography of the abdomen showed a 8.2 x 8.9 cm-sized solid
      heterogeneous mass occupying the cul-de-sac, which appeared to be in no way
      connected with the ovary. On exploratory laparotomy, the tumor mass protruded
      from the posterolateral retroperitoneum of the pelvic cavity and severely
      replaced the uterus and adnexa with the outer surface being grossly intact. It
      grossly measured 10 cm in maximal diameter. The histologic features closely
      resembled those of ovarian granulosa cell tumor. The primary extraovarian
      granulosa cell tumor is extremely rare such that in the English literature only 7
      cases have been reported to date. Of those granulosa cell tumors are especially
      rare and only two cases have been reported to arise from retroperitoneum. We
      herein present a case of retroperitoneal granulosa cell tumor with special regard
      to differential diagnosis from other solid tumors with similar histology.

PMID- 11456407
TI  - A novel silent substitution (C8516T) in exon 9 of the human PROC gene.
AB  - Protein C is a vitamin K dependent serine protease zymogen, which has a
      regulatory influence over the coagulation cascade via the inhibition of factors
      Va and VIIIa. Hereditary protein C deficiency is associated with an increased
      risk of thromboembolic disease. A multitude of families displaying protein C
      (PROC) gene defects have been reported, and a number of DNA sequence
      polymorphisms are known to occur in the PROC gene. We have identified a
      previously undescribed silent substitution (C8516T) by direct DNA sequencing in a
      Korean patient with thrombosis and protein C deficiency. In addition, a rare T
      allelic frequency (0.016) was determined in 123 patients with acquired or
      hereditary protein C deficiency.

PMID- 11456408
TI  - Neural retina of chick embryo in organ culture: effects of blockade of growth
      factors by suramin.
AB  - The neural retina is a highly organized organ whose final histoarchitecture
      depends on the presence of diverse growth factors and on their interactions with
      extracellular matrix components. However, the role of growth factors on retinal
      development is not fully understood. Suramin has been shown to produce diverse
      cellular effects via the simultaneous block of the action of several growth
      factors. We have therefore studied the effects of suramin on organotypic culture
      of chick embryo neural retina in order to gain further insights into the
      participation of growth factors in neural retinal development. Neural retina was
      incubated for 24 h with suramin at 50-200 microM and then processed to determine
      cell proliferation, nuclear morphology, and actin distribution. Suramin provoked
      extensive morphological changes revealed by a decrease in BrdU incorporation,
      alterations in cellular organization, and disruption of the outer limiting
      membrane, with the emergence of cellular elements through it. All of these
      effects were dose-dependent and markedly attenuated by the simultaneous presence
      of suramin and fibroblast growth factor 2 (FGF-2) in the culture medium. These
      findings indicate that suramin induces pleiotropic effects on the
      histoarchitecture of the chicken neural retina in organ culture and suggest that
      FGF-2 is one of the biological modulators involved in the maintenance of the
      structural organization of the chicken neural retina.

PMID- 11456409
TI  - The expression of Quox 1, a homeodomain-containing protein, in sympathetic
      ganglion cells is regulated in vitro by growth factors.
AB  - Quox 1, a quail homeobox gene, is the first vertebrate Antp-type homeobox gene to
      be described that is expressed in the forebrain. We have already shown that the
      Quox 1 protein is specifically expressed in post-mitotic sensory neurons. A
      subpopulation of sympathetic ganglion cells was also found to be labelled by anti
      Quox 1 in vitro, but it is not clear whether this protein is expressed in
      sympathetic ganglion cells in vivo and, if so, the conditions which regulate its
      expression in vitro. In the present study, we used immunocytochemistry to find
      out whether Quox 1 expression in sympathetic ganglion cells in vitro is regulated
      by environmental signals. We found that several peptide growth factors can
      regulate Quox 1 expression in cultured sympathetic ganglion cells, and that they
      do so at physiological concentration and in a variety of ways. Basic fibroblast
      growth factor (FGF-2) induces Quox 1 protein expression, whereas insulin and
      human insulin-like growth factor-I (IGF-I) down-regulate Quox 1 expression.

PMID- 11456410
TI  - Phenotypic modulation of parietal epithelial cells of Bowman's capsule in
      culture.
AB  - The origin of cobblestone-like polygonal cells (the most numerous in renal
      glomerular cell culture) remains controversial; they could be either
      dedifferentiated podocytes or parietal epithelial cells (PECs) of Bowman's
      capsule. Poor cellular outgrowth from glomeruli devoid of Bowman's capsule
      (decapsulated glomeruli) hinders podocytes being obtained without contamination
      of PECs in culture. Since podocytes are easily damaged during the isolation of
      glomeruli by the conventional sieving method, we devised a gentle isolation
      method without forced sieving, resulting in substantial numbers of arborized
      cells growing out from decapsulated glomeruli. The cells were distinctly
      different from cobblestone-like polygonal cells in their irregular and often
      arborized shape and extended long cytoplasmic processes that often crossed over
      adjacent cells. The arborized cells from decapsulated glomeruli showed intense
      staining for a podocyte-specific marker, podocalyxin, but no staining for markers
      specific to PECs (pan cadherin), mesangial cells (Thy-1) or endothelial cells
      (von Willebrand factor, RECA-1), indicating their podocyte origin. Polygonal
      cells growing out from encapsulated glomeruli were negative for podocalyxin and
      positive for pan cadherin at the peripheral cell-cell contact. Thus, the cell
      population from decapsulated glomeruli is distinctly different from that from
      encapsulated glomeruli, supporting the idea that polygonal cells originate from
      PECs, although immunocytochemical markers specific to podocytes in vivo such as
      WT1, synaptopodin, HSP27 and P-31 antigen were expressed significantly in the
      polygonal cells. Occasionally, large irregular-shaped cells appeared at the
      periphery of the outgrowths from encapsulated glomeruli. They were similar in
      shape to the arborized cells from decapsulated glomeruli but were identical in
      antigenic properties to cobblestone-like polygonal cells and thus may be named
      "pseudo-arborized cells". We conclude that PECs in culture modulate their
      phenotype to resemble podocytes.

PMID- 11456411
TI  - Establishment and characterization of tartrate-resistant acid phosphatase and
      alkaline phosphatase double positive cell lines.
AB  - Morphologically macrophage-like cells were cloned from hamster bone marrow cells
      by coculturing bone marrow cells with hamster chondrocytes. One of the clones
      (CCP-2) was characterized in the present study. CCP-2 cells were positive in an
      osteoclast marker enzyme, tartrate-resistant acid phosphatase (TRAP), alkaline
      phosphatase (ALP) and non-specific esterase (NSE). We showed CCP-2 cells degraded
      cartilage matrix and hydroxyapatite coated on Osteologic disks. A gelatinase
      secreted from CCP-2 cells was observed and purified from serum-free conditioned
      medium of the cells. N-terminal amino acid sequencing of the purified enzyme
      revealed it was matrix metalloproteinase-9. However, CCP-2 cells failed to
      express calcitonin receptors, a mature osteoclast marker, even after coculture
      with osteoblast ST2 cells in the presence of 1alpha, 25-dihydroxyvitamin D3
      [1alpha, 25-(OH)2D3]. The cells showed high affinity to types X and I but not to
      type II collagen. In addition, histochemical studies have shown the presence of
      tartrate-resistant acid phosphatase and alkaline phosphatase double positive
      cells at the secondary ossification site of the hamster humerus. From these
      observations, we concluded that CCP-2 cells are similar to osteoclast but not the
      same. CCP-2 cells are therefore important tools for investigating
      chondroclastogenesis/osteoclastogenesis and endochondral ossification.

PMID- 11456412
TI  - Effects of SCO-spondin thrombospondin type 1 repeats (TSR) in comparison to
      Reissner's fiber material on the differentiation of the B104 neuroblastoma cell
      line.
AB  - SCO-spondin is a newly identified protein that is strongly expressed in the
      subcommissural organ (SCO), an ependymal differentiation of the brain. When
      released into the cerebrospinal fluid at the entrance to the Sylvian aqueduct,
      the glycoproteins condense and form a thread-like structure, Reissner's fiber
      (RF). To analyze the role of SCO-spondin on neuronal development, we studied the
      effects induced by an oligopeptide derived from a thrombospondin type 1 repeat
      (TSR) of SCO-spondin on neuroblastoma B104 cells and compared them with the
      effects of soluble RF material containing complete SCO-spondin proteins. In low
      density cell culture, the TSR peptide first induced a notable flattening of cells
      accompanied by increased neurite outgrowth. Grouping of these differentiated B104
      cells, which later formed dense aggregates, was then observed with increasing
      time in culture. Soluble RF material induced similar morphological changes and
      neurite-promoting effects on B104 cells, although the cells remained evenly
      distributed throughout the culture time and no aggregates were visible. In high
      density cell culture, both TSR peptide and RF material induced prominent neurite
      outgrowth and subsequent rapid cell aggregation. Whereas soluble RF material
      inhibited cell proliferation, no respective effect was observed in the presence
      of the TSR peptide. A direct interaction of TSR peptide and soluble RF material
      with a B104 cell binding site was revealed by increased B104 cell metabolic
      activity by flow cytometry.

PMID- 11456413
TI  - Retroviral transduction of alveolar bone cells with a temperature-sensitive SV40
      large T antigen.
AB  - We have transduced adult human alveolar bone (AB) cells with a gene construct
      encoding a temperature-sensitive mutation of the SV40 large T antigen (tsT). Such
      cells divided rapidly, for more than 50 passages thus far, at a permissive low
      temperature (34.5 degrees C), comparable to the non-transduced parental cells at
      37 degrees C. However, the tsT-transduced AB cells failed to grow at a non
      permissive high temperature (39 degrees C) at which the T antigen is inactivated.
      Nevertheless, the cells formed mineralised nodules in vitro at both the low and
      high temperatures. Flow cytometry analysis showed that the transduced cells
      cultured at 34.5 degrees C, like the parental cells at 37 degrees C, were smaller
      and less granular than the transduced cells incubated at 39 degrees C. Moreover,
      the transduced cells grown at 34.5 degrees C were also found to express bone
      sialoprotein, osteopontin and type I collagen at levels similar to those of the
      parental cells at 37 degrees C, although osteonectin and fibronectin were down
      regulated. When the transduced cells were incubated at 39 degrees C, the
      expression of all antigens was up-regulated, particularly osteonectin. Thus, we
      have obtained long-term cultures of tsT-transduced AB cells whose growth is
      temperature-dependent and which express certain features characteristic of bone
      derived cells.

PMID- 11456414
TI  - Intrauterine oxytocin system. Compartmental distribution of oxytocin and oxytocin
      receptors in rat endometrial epithelium.
AB  - At term, uterine epithelial cells express oxytocin (OT) as well as the OT
      receptor (OTR). Like other epithelial cells, uterine epithelial cells are
      polarized and sort secretory and membrane components to the apical or the
      basolateral cell surface. We have studied the subcellular localization of OT-like
      immunoreactivity (OT-IR) and OTR-IR in rat uterine epithelium by immuno-gold
      labelling of ultrathin frozen sections. Our observations indicate that OT and OTR
      are both distributed preferentially to the apical surface of rat uterine
      epithelial cells. OT-IR showed a 6-fold apical versus basolateral preference and
      was localized in apical secretory vesicles, suggesting that uterine OT is
      released by apical exocytosis. OTR-IR was localized to the apical surface with a
      9-fold apical versus basolateral preference and was found specifically in
      association with apical microvilli. The present findings represent the first
      example of a G protein-coupled receptor that is preferentially localized on the
      microvillar compartment and support the concept of an autocrine uterine OT system
      at the apical side of the uterine epithelium.

PMID- 11456415
TI  - Evidence that a copper-metallothionein complex is responsible for fluorescence in
      acid-secreting cells of the Drosophila stomach.
AB  - Copper cells were originally identified in Drosophila midgut epithelium by their
      striking orange fluorescence in copper-fed larvae. Here, we examined copper cell
      fluorescence in light of the previous observations that (1) a similar fluorescent
      signal in yeast is produced by a complex between copper and metallothionein, and
      (2) metallothionein is expressed constitutively in the copper cell region and
      inducibly in other regions of the Drosophila midgut. Pulse-feeding experiments
      with 1 mM CuCl2 revealed that fluorescence appeared rapidly in copper cells (<5
      min) and slowly in other cells of the midgut (days), suggesting a constitutive
      cofactor in the former and an inducible cofactor in the latter. Fluorescence was
      also detected in Drosophila S2 tissue culture cells after induction of
      metallothionein synthesis by addition of CuCl2 to the growth medium. Thus,
      fluorescence coincided spatially and temporally with the expression of
      metallothionein. Fluorescence was also linked to the acid-secreting activity of
      copper cells. Fluorescence was not observed when acid secretion was inhibited by
      a mutation in the alpha spectrin gene and acidification was blocked in copper-fed
      wild-type larvae. However, acidification was restored after a 1-day chase period
      in which the fluorescent signal became sequestered within a vesicular
      compartment. We therefore conclude that copper cell fluorescence is most probably
      attributable to a cytoplasmic copper-metallothionein complex, suggesting an
      unanticipated role for metallothionein in acid-secreting cells.

PMID- 11456416
TI  - Cysteine proprotease colocalizes with vitellogenin in compound granules of the
      cockroach fat body.
AB  - A cysteine proprotease has been identified in developing embryos of the cockroach
      Blattella germanica and found to be a maternally encoded gene product that is
      transferred endocytically to the oocyte. The present study aims at establishing
      how this maternally derived proprotease is synthesized, packaged, and secreted
      during vitellogenesis. To this end, proprotease was localized
      immunocytochemically in the fat body of postmating females and its localization
      compared with that of vitellogenin over the same developmental periods. Fat
      bodies in cockroaches are comprised of two different cell types: trophocytes and
      bacteriocytes. Data show that proprotease and vitellogenin come to colocalize in
      compound granules of the fat body trophocytes. While synthesis of vitellogenin
      can be traced back to granules resulting from the coalescence of Golgi-derived
      vesicles in the trophocyte cytoplasm, proprotease appears to be localized
      predominantly on the cytolysosomes of both trophocytes and bacteriocytes. When
      probed with an anti-proprotease antiserum, bacteria are also positively labeled,
      regardless of whether they are segregated inside the cytolysosomes or free in the
      bacteriocyte cytoplasm. Since vitellogenin and proprotease colocalize within the
      same cell organelle, it is assumed that Golgi-derived vesicles, which contain
      vitellogenin, may fuse with cytolysosomes bearing proprotease to yield compound
      secretory granules. To account for the present observations, the origin and role
      of proprotease are discussed in relation to the turnover of bacteria in the fat
      body and to the requirements of endosymbiosis.

PMID- 11456417
TI  - Stem cells in a basal bilaterian. S-phase and mitotic cells in Convolutriloba
      longifissura (Acoela, Platyhelminthes).
AB  - In Platyhelminthes, totipotent stem cells (neoblasts) are supposed to be the only
      dividing cells. They are responsible for the renewal of all cell types during
      development, growth, and regeneration, a unique situation in the animal kingdom.
      In order to further characterize these cells, we have applied two
      immunocytochemical markers to detect neoblasts in different stages of the cell
      cycle in the acoel flatworm Convolutriloba longifissura: (1) the thymidine analog
      5'-bromo-2'-deoxyuridine (BrdU) to identify cells in S-phase, and (2) an antibody
      to phosphorylated histone H3 to locate mitosis. BrdU pulse-chase experiments were
      carried out to follow differentiation of neoblasts. We demonstrate the
      differentation into four labeled, differentiated cell types. S-phase cells and
      mitotic cells showed a homogenous distribution pattern throughout the body of C.
      longifissura. Two different types of S-phase cells could be distinguished
      immunocytochemically by their pattern of incorporated BrdU in the nuclei.
      Transmission electron microscopy was used to study ultrastructural characters of
      neoblasts and revealed two different stages in maturation of neoblasts, each with
      a characteristic organization of heterochromatin. The stem-cell pool of C.
      longifissura is an important prerequisite for the extraordinary mode of asexual
      reproduction and the high capacity of regeneration. A comparison of the stem-cell
      pool in Acoela and higher platyhelminth species can provide evidence for the
      phylogenetic relationships of these taxa.

PMID- 11456418
TI  - Localization of cGMP immunoreactivity and of soluble guanylyl cyclase in antennal
      sensilla of the hawkmoth Manduca sexta.
AB  - The intracellular messenger cGMP (cyclic guanosine monophosphate) has been
      suggested to play a role in olfactory transduction in both invertebrates and
      vertebrates, but its cellular location within the olfactory system has remained
      elusive. We used cGMP immunocytochemistry to determine which antennal cells of
      the hawkmoth Manduca sexta are cGMP immunoreactive in the absence of pheromone.
      We then tested which antennal cells increase cGMP levels in response to nitric
      oxide (NO) and to long pheromonal stimuli, which the male encounters close to a
      calling female moth. In addition, we used in situ hybridization to determine
      which antennal cells express NO-sensitive soluble guanylyl cyclase. In response
      to long pheromonal stimuli with NO donors present, cGMP concentrations change in
      at least a subpopulation of pheromone-sensitive olfactory receptor neurons. These
      changes in cGMP concentrations in pheromone-dependent olfactory receptor neurons
      cannot be mimicked by the addition of NO donors in the absence of pheromone. NO
      stimulates sensilla chaetica type I and II, but not pheromone-sensitive trichoid
      sensilla, to high levels of cGMP accumulation as detected by immunocytochemistry.
      In situ hybridizations show that sensilla chaetica, but not sensilla trichodea,
      express detectable levels of mRNA coding for soluble guanylyl cyclase. These
      results suggest that intracellular rises in cGMP concentrations play a role in
      information processing in a subpopulation of pheromone-sensitive sensilla in
      Manduca sexta antennae, mediated by an NO-sensitive mechanism, but not an NO
      dependent soluble guanylyl cyclase.

PMID- 11456419
TI  - Gustatory organs of Drosophila melanogaster: fine structure and expression of the
      putative odorant-binding protein PBPRP2.
AB  - In Drosophila, as in most insects, gustation is mediated by sensory hairs located
      on the external and internal parts of the proboscis and on the legs and wings. We
      describe in detail the organization and ultrastructure of the gustatory sensilla
      on the labellum and legs and the distribution of PBPRP2, a putative odorant
      binding protein, in the gustatory organs of Drosophila. The labellum carries two
      kinds of sensilla: taste bristles and taste pegs. The former have the typical
      morphology of gustatory sensilla and can be further subdivided into three
      morphological subtypes, each with a stereotyped distribution and innervation.
      Taste pegs have a unique morphology and are innervated by two receptor cells: one
      mechanoreceptor and the other a putative chemoreceptor cell. PBPRP2 is abundantly
      expressed in all adult gustatory organs on labellum, legs, and wings and in the
      internal taste organs on the proboscis. In contrast to olfactory organs, where
      PBPRP2 is expressed in the epidermis, this protein is absent from the epidermis
      of labial palps and legs. In the taste bristles of the labellum and legs, PBPRP2
      is localized in the crescent-shaped lumen of the sensilla, and not in the lumen
      where the dendrites of the gustatory neurons are found, making a function in
      stimulus transport unlikely in these sensilla. In contrast, PBPRP2 in peg
      sensilla is expressed in the inner sensillum-lymph cavity and is in contact with
      the dendrites. Thus, PBPRP2 could be involved as a carrier for hydrophobic
      ligands, e.g., bitter tastants, in these sensilla.

PMID- 11456420
TI  - Morphology and distribution of setae on the antennules of the Caribbean spiny
      lobster Panulirus argus reveal new types of bimodal chemo-mechanosensilla.
AB  - This study describes the morphology and distribution of setae on the lateral and
      medial flagella of the antennules of the spiny lobster Panulirus argus in an
      effort to identify antennular chemoreceptors in addition to the well-studied
      aesthetasc chemosensilla. Setae were examined using light and electron
      microscopy, and their distribution on flagellar annuli was analyzed. We
      identified ten setal types based on external morphology: hooded, plumose, short
      setuled, long simple, medium simple, short simple, aesthetasc, guard, companion,
      and asymmetric setae, with the last four types being unique to the "tuft" located
      on the distal half of the lateral flagellum. The three setal types whose
      ultrastructure was examined--hooded, long simple, and medium simple setae--had
      characteristics of bimodal (chemo-mechanoreceptive) sensilla. The antennules have
      four distinct annular types based on their setal complement, as shown by cluster
      analysis. This basic distribution of non-tuft setal types is similar for both
      lateral and medial flagella. Annuli in the tuft region have tuft setal types
      superimposed on a basic organization of non-tuft setal types. These results show
      that the antennules possess a diverse set of setae, that these setae have a
      highly ordered arrangement on the antennules, that at least four (and probably
      many more) of these setal types are chemosensilla, and suggest that most
      antennular chemosensilla are bimodally sensitive.

PMID- 11456421
TI  - Rhogocytes (pore cells) as the site of hemocyanin biosynthesis in the marine
      gastropod Haliotis tuberculata.
AB  - Rhogocytes (pore cells) are specific molluscan cell types that are scattered
      throughout the connective tissues of diverse body parts. We have identified
      rhogocytes in large numbers in tissue taken from mantle, foot and midgut gland of
      the abalone Haliotis tuberculata (Vetigastropoda). Within cisternae of the
      endoplasmic reticulum, particles are visible that resemble, in shape and size,
      hemocyanin molecules, the respiratory protein of many molluscs.
      Immunohistochemical experiments using hemocyanin-specific antibodies demonstrated
      that these cells contain hemocyanin. In situ hybridization with a cDNA probe
      specific for Haliotis hemocyanin showed that hemocyanin-specific mRNA is present
      in rhogocytes, which confirmed that they are the site of hemocyanin biosynthesis
      in this gastropod. A possible path of hemocyanin release into the hemolymph is
      discussed. Also in the vetigastropod Megathura crenulata, many rhogocytes could
      be detected. However, they lacked hemocyanin molecules which, together with
      published data, indicates a seasonal expression of hemocyanin in this animal.

PMID- 11456422
TI  - An integration of feminist and self-psychological approaches to bulimia nervosa.
AB  - Theoretical frameworks have guided approaches to treatment for the eating
      disorders. While unitary models were characteristic of earlier eras, more recent
      formulations have attempted to improve understanding by integrating various
      schools of thought (1). Several of these have placed cultural factors in the
      context of individual and familial predispositions. A weakness of these models
      has been the relative lack of understanding of the means by which these cultural
      values create mechanisms for expression of these disorders in specific women. In
      this manuscript I will explore the theoretical framework which places eating
      disorders in the context of socialization and culture, and integrate this with
      our current understanding of the individual psychopathological factors that
      enhance a woman's susceptibility to eating disorders. This exploration of
      specific mechanisms has implications for the development of efficacious models of
      treatment.

PMID- 11456423
TI  - Validating the Eating Disorder Inventory-2 (EDI-2) in Sweden.
AB  - OBJECTIVE: To validate the Eating Disorder Inventory-2 (EDI-2) on a Swedish
      population by investigating differences between 1) young women with eating
      disorder symptoms (patients and non-patients), and normal controls and 2)
      patients with different eating disorder diagnoses, regarding symptom load and
      psychological characteristics. Another objective was to update EDI as a screening
      instrument METHOD: Patients (n=194) with DSM-IV confirmed eating disorder
      diagnoses (anorexia nervosa AN; bulimia nervosa BN; eating disorder not otherwise
      specified, EDNOS) were compared vvith each other and with randomly selected and
      matched controls consisting of young women with self-reported eating disorder
      symptoms (n=51) and women without such symptoms (n=188). RESULTS: In general,
      women vvith eating disorderproblems, whether or not they were patients, scored
      significantly higher on both symptoms and personality characteristics compared to
      normal controls. Patients with DSM verified eating disorders did not differ from
      women with self-reported eating disorders symptoms on body dissatisfaction,
      perfectionism and impulsiveness. Women with self-reported symptoms did not differ
      from women without symptoms on interpersonal distrust and maturity fears. Amongst
      the patient groups, BN patients scored highest, and AN patients lowest, on self
      reported pathology. Most of the EDI-2 scales and all the three indexes had
      acceptable specificity and sensitivity. CONCLUSION: EDI-2 discriminates well
      between women with eating disorder symptoms and normal controls, but responses
      from patients with AN should be interpreted with care. The EDI-2 indexes are
      especially recommended for screening purposes.

PMID- 11456424
TI  - Eating disorders and sexual abuse.
AB  - This review examines the current debate on the role that sexual and physical
      abuse may play in predisposing to eating disorders in women. Despite some
      discordant opinions, clinicians agree that the experience of abuse in early
      childhood may be important for understanding the complex genesis of the eating
      disorders of some women. Three groups of studies are presented: those in which no
      connections emerge between sexual abuse and eating disorders, those in which a
      strong link is present and those in which the results refer to a multifactorial
      interpretative model. Some of the main symptoms, such as reactualization of the
      trauma, dissociation, personality disorders, pathological relationship with food,
      distortion of body image, suicide attempts and self-inflicted punishment that
      victims of abuse and eating disordered subjects share are examined.

PMID- 11456425
TI  - The stepped-care approach in anorexia nervosa and bulimia nervosa: progress and
      problems.
AB  - The stepped-care approach is based on the assumption that treatment should be
      less intensive and hence less expensive and intrusive at the start. Current data
      suggest that cognitive behaviour therapy (CBT) should be the preferred first
      treatment for bulimia nervosa (BN) patients. By comparison with the numerous
      trials supporting its efficacy, in fact, the evidence sustaining similar
      therapies, e.g. interpersonal psychotherapy (IPT) or pharmacological therapy, is
      weaker. There are now sufficient data to justify the use of less intensive and
      shorter treatment (i.e. psychoeducational groups and self-help) in less serious
      cases. If CBT fails, IPT, pharmacological treatment, alternative psychotherapies,
      modified CBT, day-hospital and inpatient treatments are available, though it is
      not clear which is the most efficacious second step. The lower level of stepped
      care models seems inapplicable in anorexia nervosa (AN). Current data do not
      suggest first-choice therapies. Management of this disorder is very expensive and
      requires a very high level of professional treatment and the highest level of the
      service hierarchy (intensive outpatient treatment, day-hospital, or inpatient
      treatment). One of the major obstacles to the employment of the stepped-care
      approach in eating disorders is that few therapists are trained in CBT and IPT.
      Academic structures and the scientific societies of eating disorders should
      promote training and dissemination of these effective forms of treatment.

PMID- 11456426
TI  - Eating concerns in East Asian immigrants: relationships between acculturation,
      self-construal, ethnic identity, gender, psychological functioning and eating
      concerns.
AB  - OBJECTIVE: Eating concerns in East Asian immigrants were assessed and their
      association with acculturation status, self-construal, ethnic identity, gender
      and psychological functioning was examined. METHOD: One-hundred and fifty non
      clinical East Asian immigrants (75 males, 75 females) were administered a battery
      of psychometrically established measures with satisfactory reliability and
      validity. RESULTS: Females were more prone to eating concerns and these were
      positively related to symptoms of psychological distress. Acculturation, self
      construal, ethnic identity and psychological functioning were not related to
      desire to be thinner, feeling guilt after eating, fear of being overweight nor
      preoccupation with the thought of having fat on one's body. Collective self
      esteem and symptoms of psychological distress were positively related to feeling
      discomfort after eating sweets, while interdependent self-construal and
      assimilation were negatively related. DISCUSSION: Culturally relevant variables,
      namely acculturation, self-construal and ethnic identity, were related to only
      certain facets of eating concerns. The findings suggest the importance of
      assessing discrete, psychologically-relevant facets of culture rather than more
      global constructs such as westernization when examining eating concerns in
      immigrant populations.

PMID- 11456427
TI  - Information from your family doctor. What should I know about seizures and
      epilepsy?

PMID- 11456428
TI  - Adolescent idiopathic scoliosis: review and current concepts.
AB  - Adolescent idiopathic scoliosis is present in 2 to 4 percent of children between
      10 and 16 years of age. It is defined as a lateral curvature of the spine greater
      than 10 degrees accompanied by vertebral rotation. It is thought to be a
      multigene dominant condition with variable phenotypic expression. Scoliosis can
      be identified by the Adam's forward bend test during physical examination. Severe
      pain, a left thoracic curve or an abnormal neurologic examination are red flags
      that point to a secondary cause for spinal deformity. Specialty consultation and
      magnetic resonance imaging are needed if red flags are present. Of adolescents
      diagnosed with scoliosis, only 10 percent have curves that progress and require
      medical intervention. The main risk factors for curve progression are a large
      curve magnitude, skeletal immaturity and female gender. The likelihood of curve
      progression can be estimated by measuring the curve magnitude using the Cobb
      method on radiographs and by assessing skeletal growth potential using Tanner
      staging and Risser grading.

PMID- 11456429
TI  - Medications in the breast-feeding mother.
AB  - Prescribing medications for a breast-feeding mother requires weighing the
      benefits of medication use for the mother against the risk of not breast-feeding
      the infant or the potential risk of exposing the infant to medications. A drug
      that is safe for use during pregnancy may not be safe for the nursing infant. The
      transfer of medications into breast milk depends on a concentration gradient that
      allows passive diffusion of nonionized, non-protein-bound drugs. The infant's
      medication exposure can be limited by prescribing medications to the breast
      feeding mother that are poorly absorbed orally, by avoiding breast-feeding during
      times of peak maternal serum drug concentration and by prescribing topical
      therapy when possible. Mothers of premature or otherwise compromised infants may
      require altered dosing to avoid drug accumulation and toxicity in these infants.
      The most accurate and up-to-date sources of information, including Internet
      resources and telephone consultations, should be used.

PMID- 11456430
TI  - Should we prescribe antibiotics for acute bronchitis?
AB  - OBJECTIVES: People with acute bronchitis may show little evidence of bacterial
      infection. If effective, antibiotics could shorten the course of the disease.
      However, if they are not effective, the risk of antibiotic resistance may be
      increased. The objective of this review was to assess the effects of antibiotic
      treatment in patients with a clinical diagnosis of acute bronchitis. SEARCH
      STRATEGY: The authors searched MEDLINE, Embase, reference lists of articles,
      personal collections up to 1996 and Sci-search from 1989 to 1996. SELECTION
      CRITERIA: Randomized trials comparing any antibiotic therapy with placebo in
      acute bronchitis. DATA COLLECTION AND ANALYSIS: At least two reviewers extracted
      data and assessed trial quality. PRIMARY RESULTS: The results of eight trials
      involving 750 patients from eight years of age to 65 and older and including
      smokers and nonsmokers were included. The quality of the trials was variable. A
      variety of outcome measures was assessed. In many cases, only outcomes that
      showed a statistically significant difference between groups were reported.
      Overall, patients taking antibiotics had slightly better outcomes than those
      taking placebo. They were less likely to report feeling unwell at a follow-up
      visit (odds ratio, 0.42; 95 percent confidence interval [CI] 0.22 to 0.82), to
      show no improvement on physician assessment (odds ratio, 0.43; CI, 0.23 to 0.79)
      or to have abnormal lung findings (odds ratio, 0.33; CI, 0.13 to 0.86), and had a
      more rapid return to work or usual activities (weighted mean difference, 0.7 days
      earlier; CI, 0.2 to 1.3). Antibiotic-treated patients reported significantly more
      adverse effects (odds ratio, 1.64; CI, 1.05 to 2.57), such as nausea, vomiting,
      headache, skin rash or vaginitis. REVIEWERS' CONCLUSIONS: Antibiotics appear to
      have a modest beneficial effect in the treatment of acute bronchitis, with a
      correspondingly small risk of adverse effects. The benefits of antibiotics may be
      overestimated in this analysis because of the tendency of published reports to
      include complete data only on outcomes found to be statistically significant.

PMID- 11456431
TI  - Photo quiz. New-onset digital clubbing.

PMID- 11456432
TI  - ACOG issues guidelines on fetal macrosomia. American College of Obstetricians and
      Gynecologists.

PMID- 11456433
TI  - Prevention of HIV infection in adolescents.

PMID- 11456434
TI  - Women in medicine.

PMID- 11456435
TI  - Referrals from scoliosis screenings.

PMID- 11456436
TI  - Management of MVP with antibiotic prophylaxis.

PMID- 11456437
TI  - Common anorectal conditions: Part II. Lesions.
AB  - Patients with a wide variety of anorectal lesions present to family physicians.
      Most can be successfully managed in the office setting. A high index of suspicion
      for cancer should be maintained and all patients should be questioned about
      relevant family history or other indications for cancer screening. Patients with
      condylomata acuminata must be examined for human papillomavirus infection
      elsewhere after treatment of the presenting lesions. Their sexual partners should
      also be counseled and screened. Both surgical and nonsurgical treatments are
      available for the pain of anal fissure. Infection in the anorectal area may
      present as different types of abscesses, cryptitis, fistulae or perineal sepsis.
      Fistulae may result from localized infection or indicate inflammatory bowel
      disease. Protrusion of tissue through the anus may be due to hemorrhoids, mucosal
      prolapse, polyps or other lesions.

PMID- 11456438
TI  - Advances in the treatment of epilepsy.
AB  - Significant advances have been made in the diagnosis and treatment of epilepsy
      over the past decade. With the advent of electroencephalographic video
      monitoring, physicians are now able to reliably differentiate epilepsy from other
      conditions that can mimic it, such as pseudoseizures. In addition, neuroimaging
      has changed the way treatment for difficult epilepsy is approached. As a result,
      the classification systems that have been in use since the early 1980s are
      currently being revised. A broader range of treatment options for epilepsy is now
      available. Many new antiepileptic drugs have become available in recent years,
      including felbamate, gabapentin, lamotrigine, topiramate, tiagabine,
      levetiracetam, oxcarbazepine and zonisamide. These medications offer options for
      patients with epilepsy whose seizures cannot be controlled using the classic
      agents. Several classic antiepileptic drugs have been modified and reformulated.
      The ketogenic diet has resurfaced as a treatment option in certain types of
      epilepsy. The vagus nerve stimulator, approved in 1997, represents a completely
      new treatment modality for patients with seizures not controlled by medications.
      Epilepsy surgery is now a well-documented and effective treatment for some
      patients with intractable epilepsy.

PMID- 11456440
TI  - Developmental clustering of ion channels at and near the node of Ranvier.
AB  - Voltage-gated Na(+) and K(+) channels are localized to distinct subcellular
      domains in mammalian myelinated nerve fibers. Specifically, Na(+) channels are
      clustered in high densities at nodes of Ranvier, while K(+) channels are found in
      juxtaparanodal zones just beyond regions of axoglial contact where sequential
      layers of the myelin sheath terminate. Specific targeting, clustering, and
      maintenance of these channels in their respective domains are essential to
      achieve high conduction velocities of action potential propagation. The cellular,
      molecular, and developmental mechanisms that exist to achieve this neuronal
      specialization are discussed and reviewed. Current evidence points to a prominent
      role in channel clustering played by myelinating glial cells, and sites of
      axoglial contact in particular.

PMID- 11456441
TI  - Transdifferentiation of the ventral retinal pigmented epithelium to neural retina
      in the growth arrest specific gene 1 mutant.
AB  - During eye development, retinal pigmented epithelium (RPE) and neural retina (NR)
      arise from a common origin, the optic vesicle. One of the early distinctions of
      RPE from NR is the reduced mitotic activity of the RPE. Growth arrest specific
      gene 1 (Gas1) has been documented to inhibit cell cycle progression in vitro (G.
      Del Sal et al., 1992, Cell 70, 595--607). We show here that the expression
      pattern of Gas1 in the eye supports its negative role in RPE proliferation. To
      test this hypothesis, we generated a mouse carrying a targeted mutation in the
      Gas1 locus. Gas1 mutant mice have microphthalmia. Histological examination
      revealed that the remnant mutant eyes are ingressed from the surface with minimal
      RPE and lens, and disorganized eyelid, cornea, and NR. Analysis of the Gas1
      mutant indicates that there is overproliferation of the outer layer of optic cup
      (E10.5) immediately after the initial specification of the RPE. This defect is
      specific to the ventral region of the RPE. Using molecular markers for RPE (Mi
      and Tyrp2) and NR (Math5), we demonstrate that there is a gradual loss of Mi and
      Tyrp2 expression and an appearance of Math5 expression in the mutant ventral RPE
      region, indicating that this domain becomes respecified to NR. This "ectopic" NR
      develops as a mirror image of the normal NR and is entirely of ventral identity.
      Our data not only support Gas1's function in regulating cell proliferation, but
      also uncover an unexpected regional-specific cell fate change associated with
      dysregulated growth. Furthermore, we provide evidence that the dorsal and ventral
      RPEs are maintained by distinct genetic components.

PMID- 11456442
TI  - Growth arrest specific gene 1 is a positive growth regulator for the cerebellum.
AB  - Postnatal cerebellum development involves the generation of granule cells and
      Bergmann glias (BGs). The granule cell precursors are located in the external
      germinal layer (EGL) and the BG precursors are located in the Purkinje layer
      (PL). BGs extend their glial fibers into the EGL and facilitate granule cells'
      inward migration to their final location. Growth arrest specific gene 1 (Gas1)
      has been implicated in inhibiting cell-cycle progression in cell culture studies
      (G. Del Sal et al., 1992, Cell 70, 595--607). However, its growth regulatory
      function in the CNS has not been described. To investigate its role in cerebellar
      growth, we analyzed the Gas1 mutant mice. At birth, wild-type and mutant mice
      have cerebella of similar size; however, mature mutant cerebella are less than
      half the size of wild-type cerebella. Molecular and cellular examinations
      indicate that Gas1 mutant cerebella have a reduced number of granule cells and BG
      fibers. We provide direct evidence that Gas1 is required for normal levels of
      proliferation in the EGL and the PL, but not for their differentiation.
      Furthermore, we show that Gas1 is specifically and coordinately expressed in both
      the EGL and the BGs postnatally. These results support Gas1 as a common genetic
      component in coordinating EGL cell and BG cell proliferation, a link which has
      not been previously appreciated.

PMID- 11456443
TI  - Evidence for a mesodermal embryonic regulator of the sea urchin CyIIa gene.
AB  - The CyIIa gene of the sea urchin embryo is a model for study of cis-regulation
      downstream of cell-type specification, as CyIIa transcription follows the
      specification and initial differentiation of the embryonic domains in which it is
      expressed. These are the skeletogenic and secondary mesenchyme and gut. We
      carried out a detailed structural and functional analysis of a cis-regulatory
      region of this gene, extending 780 bp upstream and 125 bp downstream of the
      transcription start site, that had been shown earlier to reproduce faithfully the
      complex and dynamic CyIIa pattern of expression. This analysis revealed that the
      overall pattern of expression of the CyIIa gene appears to be governed mainly by
      two independent sets of DNA elements, which are target sites for specific
      proteins present in blastula-stage nuclear extract. One type of element, which
      controls a dynamic program of expression in both skeletogenic and secondary
      mesenchyme cells, contains the consensus-binding site for a member of the ets
      transcription factor family. The other, which is responsible for the terminal or
      permanent phase of CyIIa expression in the gut, shares homologies with the late
      module of the endoderm-specific Endo16 gene (endo16 Module B). Oligonucleotides
      containing replicas of these two target sites fused upstream of a sea urchin
      basal promoter are sufficient to confer accurate mesenchyme and late gut
      expression of an injected GFP construct. The finding of a single protein target
      site that recapitulates CyIIa expression in both primary and secondary mesenchyme
      cells suggests the existence of a pan-mesodermal gene expression program in the
      sea urchin embryo.

PMID- 11456444
TI  - Microarray-based analysis of early development in Xenopus laevis.
AB  - In order to examine transcriptional regulation globally, during early vertebrate
      embryonic development, we have prepared Xenopus laevis cDNA microarrays. These
      prototype embryonic arrays contain 864 sequenced gastrula cDNA. In order to
      analyze and store array data, a microarray analysis pipeline was developed and
      integrated with sequence analysis and annotation tools. In three independent
      experimental settings, we demonstrate the power of these global approaches and
      provide optimized protocols for their application to molecular embryology. In the
      first set, by comparing maternal versus zygotic transcription, we document groups
      of genes that are temporally regulated. This analytical approach resulted in the
      discovery of novel temporally regulated genes. In the second, we examine changes
      in gene expression spatially during development by comparing dorsal and ventral
      mesoderm dissected from early gastrula embryos. We have discovered novel genes
      with spatial enrichment from these experiments. Finally, we use the prototype
      microarray to examine transcriptional responses from embryonic explants treated
      with activin. We selected genes (two of which are novel) regulated by activin for
      further characterization. All results obtained by the arrays were independently
      tested by RT-PCR or by in situ hybridization to provide a direct assessment of
      the accuracy and reproducibility of these approaches in the context of molecular
      embryology.

PMID- 11456445
TI  - Dynamic domains of gene expression in the early avian forebrain.
AB  - The expression domains of genes implicated in forebrain patterning often share
      borders at specific anteroposterior positions. This observation lies at the heart
      of the prosomeric model, which proposes that such shared borders coincide with
      proposed compartment boundaries and that specific combinations of genes expressed
      within each compartment are responsible for its patterning. Thus, genes such as
      Emx1, Emx2, Pax6, and qin (Bf1) are seen as being responsible for specifying
      different regions in the forebrain (diencephalon and telencephalon). However, the
      early expression of these genes, before the appearance of putative compartment
      boundaries, has not been characterized. In order to determine whether they have
      stable expression domains before this stage, we have compared mRNA expression of
      each of the above genes, relative both to one another and to morphological
      landmarks, in closely staged chick embryos. We find that, between HH stage 8 and
      HH stage 13, each of the genes has a dynamic spatial and temporal expression
      pattern. To test for autonomy of gene expression in the prosencephalon, we
      grafted tissue from this region to more caudal positions in the neural tube and
      analyzed for expression of Emx1, Emx2, qin, or Pax6. We find that gene expression
      is autonomous in prosencephalic tissue from as early as HH stage 8. In the case
      of Emx1, our data suggest that, from as early stage 8, presumptive telencephalic
      tissue also is committed to express this gene. We propose that early patterning
      along the anteroposterior axis of the presumptive telencephalon occurs across a
      field that is subdivided by different combinations of genes, with some
      overlapping areas, but without either sharp boundaries or stable interfaces
      between expression domains.

PMID- 11456446
TI  - Conservation of Hox/ParaHox-related genes in the early development of a
      cnidarian.
AB  - To clarify the relationship between axial patterning in cnidarians and
      bilaterians, we have investigated the embryonic development of the hydrozoan
      Podocoryne carnea. The expression of Hox-like homeobox genes was analyzed by RT
      PCR and in situ hybridization. Cnox1-Pc, an anterior Hox gene, is a maternal
      message. It is present throughout larval development, first weakly in all
      blastomeres and later restricted mostly to the anterior pole of the planula. Gsx,
      an anterior ParaHox gene, is first seen in the anterior endoderm but also extends
      into posterior regions. Cnox4-Pc, an orphan Hox-like gene, is expressed in the
      egg as a ring-shaped cloud around the germinal vesicle. After fertilization, the
      message remains in most animal blastomeres. When the embryo elongates in late
      blastula, staining is restricted to a few cells at the posterior pole where
      gastrulation will start. However, once gastrulation starts, the Cnox4-Pc signal
      disappears and is absent in later stages of larval development. Phylogenetic
      analysis shows that not all cnidarian Hox-like genes have recognizable
      orthologues in bilaterian groups. However, the expression analysis of Cnox1-Pc
      and Gsx correlates to some extent with the expression pattern of cognate genes of
      bilaterians, confirming the conservation of genes involved in organizing animal
      body plans and their putative common ancestral origin.

PMID- 11456447
TI  - Crossing the floor plate triggers sharp turning of commissural axons.
AB  - During development of the vertebrate CNS, commissural axons initially grow
      circumferentially toward the ventral midline floor plate. After crossing the
      floor plate, they abruptly change their trajectory from the circumferential to
      the longitudinal axis. Although recent studies have unraveled the mechanisms that
      control navigation of these axons along the circumferential axis, those that
      result in the transition from circumferential to longitudinal trajectory remain
      unknown. Here, we examined whether an interaction with the floor plate is a
      prerequisite for the initiation of trajectory transition of commissural axons,
      using in vitro preparations of the rat metencephalon. We found that commissural
      axons in the metencephalon, once having crossed the floor plate, turned sharply
      to grow longitudinally. In contrast, axons extending in floor plate-deleted
      preparations, continued to grow circumferentially, ignoring the hypothetical
      turning point. These results suggest that a prior interaction of commissural
      axons with floor plate cells is a key step for these axons to activate a
      navigation program required for their change in axonal trajectory from the
      circumferential to the longitudinal axis.

PMID- 11456448
TI  - Mesoderm formation in Eleutherodactylus coqui: body patterning in a frog with a
      large egg.
AB  - The direct developing frog, Eleutherodactylus coqui, develops from a large egg
      (diameter 3.5 mm). To investigate the effect of egg size on germ-layer formation,
      we studied mesoderm formation in E. coqui and compared it to that of Xenopus
      laevis (diameter 1.3 mm). First, we identified the position of prospective
      mesoderm in the 16-cell E. coqui embryo by cell-lineage tracing. Although the
      animal blastomeres are small, they form most of the blastocoel roof and make
      extensive contributions to some mesodermal tissues. Second, we performed
      recombinant analysis with X. laevis animal caps to define the distribution of
      mesoderm-inducing activity. Mesoderm-inducing activity in E. coqui was restricted
      around the marginal zone with strong activity in the superficial cells. Neither
      the vegetal pole nor the blastocoel floor had activity, although these same
      regions from X. laevis induced mesoderm. Third, we cloned Ecbra, a homologue of
      Xbra, an early mesoderm marker in X. laevis. Ecbra was expressed in the marginal
      ring close to the surface, similar to X. laevis, but E. coqui had weaker
      expression on the dorsal side. Our results suggest that mesoderm formation is
      shifted more animally and superficially in E. coqui compared to X. laevis.

PMID- 11456449
TI  - Nodal regulates trophoblast differentiation and placental development.
AB  - Nodal has been thought to be an embryo-specific factor that regulates
      development, but nodal is also expressed in the mouse placenta beginning at
      midgestation, specifically in the spongiotrophoblasts. In an insertional null
      nodal mutant, not only is embryonic development disrupted, but mouse placental
      development is also grossly altered with the loss of the diploid
      spongiotrophoblasts and labyrinth and an expansion of the polyploid giant cell
      layer. A hypomorphic mutation in nodal results in an expansion of the giant cell
      and spongiotrophoblast layers, and a decrease in labyrinthine development.
      Expression of nodal in trophoblast cell cultures is sufficient to inhibit
      trophoblast giant cell differentiation, demonstrating that nodal can act directly
      on trophoblasts. The mechanism of nodal action includes the inhibition of junB
      gene transcription. These results suggest that nodal may be involved in
      redirecting trophoblast fate towards the midgestational expansion of the
      labyrinth region while maintaining the thin layer of trophoblast giant cells and
      the underlying layer of spongiotrophoblasts that form the boundary between the
      maternal and extraembryonic compartments.

PMID- 11456450
TI  - Hedgehog signalling is required for maintenance of myf5 and myoD expression and
      timely terminal differentiation in zebrafish adaxial myogenesis.
AB  - Hedgehog proteins have been implicated in the control of myogenesis in the medial
      vertebrate somite. In the mouse, normal epaxial expression of the myogenic
      transcription factor gene myf5 is dependent on Sonic hedgehog. Here we examine in
      zebrafish the interaction between Hedgehog signals, the expression of myoD family
      genes, including the newly cloned zebrafish myf5, and slow myogenesis. We show
      that Sonic hedgehog is necessary for normal expression of both myf5 and myoD in
      adaxial slow muscle precursors, but not in lateral paraxial mesoderm. Expression
      of both genes is initiated normally in rostral presomitic mesoderm in sonic you
      mutants, which lack all Sonic hedgehog. Similar initiation continues during
      tailbud outgrowth when the cells forming caudal somites are generated. However,
      adaxial cells in sonic you embryos are delayed in terminal differentiation and
      caudal adaxial cells fail to maintain myogenic regulatory factor expression.
      Despite these defects, other signals are able to maintain, or reinitiate, some
      slow muscle development in sonic you mutants. In the cyclops mutant, the absence
      of floorplate-derived Tiggywinkle hedgehog and Sonic hedgehog has no discernible
      effect on slow adaxial myogenesis. Similarly, the absence of notochord-derived
      Sonic hedgehog and Echidna hedgehog in mutants lacking notochord delays, but does
      not prevent, adaxial slow muscle development. In contrast, removal of both Sonic
      hedgehog and a floorplate signal, probably Tiggywinkle hedgehog, from the
      embryonic midline in cyclops;sonic you double mutants essentially abolishes slow
      myogenesis. We conclude that several midline signals, likely to be various
      Hedgehogs, collaborate to maintain adaxial slow myogenesis in the zebrafish
      embryo. Moreover, the data demonstrate that, in the absence of this required
      Hedgehog signalling, expression of myf5 and myoD is insufficient to commit cells
      to adaxial myogenesis.

PMID- 11456451
TI  - In vivo imaging indicates muscle fiber dedifferentiation is a major contributor
      to the regenerating tail blastema.
AB  - During tail regeneration in urodele amphibians such as axolotls, all of the
      tissue types, including muscle, dermis, spinal cord, and cartilage, are
      regenerated. It is not known how this diversity of cell types is reformed with
      such precision. In particular, the number and variety of mature cell types in the
      remaining stump that contribute to the blastema is unclear. Using Nomarski
      imaging, we followed the process of regeneration in the larval axolotl tail.
      Combining this with in vivo fluorescent labeling of single muscle fibers, we show
      that mature muscle dedifferentiates. Muscle dedifferentiation occurs by the
      synchronous fragmentation of the multinucleate muscle fiber into mononucleate
      cells followed by rapid cell proliferation and the extension of cell processes.
      We further show that direct clipping of the muscle fiber and severe tissue damage
      around the fiber are both required to initiate dedifferentiation. Our
      observations also make it possible to estimate for the first time how many of the
      blastema cells arise specifically from muscle dedifferentiation. Calculations
      based on our data suggest that up to 29% of nondermal-derived cells in the
      blastema come from dedifferentiation of mature muscle fibers. Overall, these
      results show that endogenous multinucleate muscle fibers can dedifferentiate into
      mononucleate cells and contribute significantly to the blastema.

PMID- 11456452
TI  - The zinc finger protein DIE-1 is required for late events during epithelial cell
      rearrangement in C. elegans.
AB  - The mechanism by which epithelial cells undergo directed rearrangement is central
      to morphogenesis, yet the regulation of these movements remains poorly
      understood. We have investigated epithelial cell rearrangement (intercalation) in
      the dorsal hypodermis, or embryonic epidermis, of the C. elegans embryo by
      analyzing the die-1(w34) mutant, which fails to undergo normal intercalation.
      Dorsal hypodermal cells of die-1(w34) homozygous embryos initiate but fail to
      complete the process of intercalation. Multiphoton microscopy reveals that
      intercalating cells extend monopolar, basolateral protrusions in their direction
      of migration; posterior dorsal hypodermal cells in die-1(w34) mutants appear to
      extend protrusions normally, but fail to translocate their cell bodies to
      complete rearrangement. Despite abnormal intercalation, the subsequent
      morphogenetic movements that enclose the embryo with epithelial cells and the
      process of dorsal cell fusion still occur. However, elongation of the embryo into
      a wormlike shape is disrupted in die-1(w34) embryos, suggesting that
      intercalation may be necessary for subsequent elongation of the embryo. Actin
      filaments are not properly organized within the dorsal hypodermis of die-1(w34)
      embryos, consistent with intercalation's being a necessary prerequisite for
      elongation. The die-1 gene encodes a C2H2 zinc finger protein containing four
      fingers, which likely acts as a transcriptional regulator. DIE-1 is present in
      the nuclei of hypodermal, muscle, gut, and pharyngeal cells; its distribution
      suggests that DIE-1 acts in each of these tissues to regulate morphogenetic
      movements. die-1(w34) mutants display morphogenetic defects in the pharynx, gut,
      and muscle quadrants, in addition to the defects in the dorsal hypodermis,
      consistent with the DIE-1 expression pattern. Mosaic analysis indicates that DIE
      1 is autonomously required in the posterior dorsal hypodermis for intercalation.
      Our analysis documents for the first time the dynamics of protrusive activity
      during epithelial cell rearrangement. Moreover, our analysis of die-1 shows that
      the events of epithelial cell rearrangement are under transcriptional control,
      and that early and later phases of epithelial cell rearrangement are genetically
      distinguishable.

PMID- 11456453
TI  - Overexpression of Smad2 reveals its concerted action with Smad4 in regulating TGF
      beta-mediated epidermal homeostasis.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily are
      critical regulators for epithelial growth and can alter the differentiation of
      keratinocytes. Transduction of TGF-beta signaling depends on the phosphorylation
      and activation of Smad proteins by heteromeric complexes of ligand-specific type
      I and II receptors. To understand the function of TGF-beta and activin-specific
      Smad, we generated transgenic mice that overexpress Smad2 in epidermis under the
      control of keratin 14 promoter. Overexpression of Smad2 increases endogenous
      Smad4 and TGF-beta 1 expression while heterozygous loss of Smad2 reduces their
      expression levels, suggesting a concerted action of Smad2 and -4 in regulating
      TGF-beta signaling during skin development. These transgenic mice have delayed
      hair growth, underdeveloped ears, and shorter tails. In their skin, there is
      severe thickening of the epidermis with disorganized epidermal architecture,
      indistinguishable basement membrane, and dermal fibrosis. These abnormal
      phenotypes are due to increased proliferation of the basal epidermal cells and
      abnormalities in the program of keratinocyte differentiation. The ectodermally
      derived enamel structure is also abnormal. Collectively, our study presents the
      first in vivo evidence that, by providing an auto-feedback in TGF-beta signaling,
      Smad2 plays a pivotal role in regulating TGF-beta-mediated epidermal homeostasis.

PMID- 11456454
TI  - The spatial and temporal expression of Ch-en, the engrailed gene in the
      polychaete Chaetopterus, does not support a role in body axis segmentation.
AB  - We are interested in understanding whether the annelids and arthropods shared a
      common segmented ancestor and have approached this question by characterizing the
      expression pattern of the segment polarity gene engrailed (en) in a basal
      annelid, the polychaete Chaetopterus. We have isolated an en gene, Ch-en, from a
      Chaetopterus cDNA library. Genomic Southern blotting suggests that this is the
      only en class gene in this animal. The predicted protein sequence of the 1.2-kb
      cDNA clone contains all five domains characteristic of en proteins in other taxa,
      including the en class homeobox. Whole-mount in situ hybridization reveals that
      Ch-en is expressed throughout larval life in a complex spatial and temporal
      pattern. The Ch-en transcript is initially detected in a small number of neurons
      associated with the apical organ and in the posterior portion of the
      prototrochophore. At later stages, Ch-en is expressed in distinct patterns in the
      three segmented body regions (A, B, and C) of Chaetopterus. In all segments, Ch
      en is expressed in a small set of segmentally iterated cells in the CNS. In the A
      region, Ch-en is also expressed in a small group of mesodermal cells at the base
      of the chaetal sacs. In the B region, Ch-en is initially expressed broadly in the
      mesoderm that then resolves into one band/segment coincident with morphological
      segmentation. The mesodermal expression in the B region is located in the
      anterior region of each segment, as defined by the position of ganglia in the
      ventral nerve cord, and is involved in the morphogenesis of segment-specific
      feeding structures late in larval life. We observe banded mesodermal and
      ectodermal staining in an anterior-posterior sequence in the C region. We do not
      observe a segment polarity pattern of expression of Ch-en in the ectoderm, as is
      observed in arthropods.

PMID- 11456455
TI  - Calmodulin antagonists inhibit T-type Ca(2+) currents in mouse spermatogenic
      cells and the zona pellucida-induced sperm acrosome reaction.
AB  - The sperm acrosome reaction (AR) is a regulated exocytotic process required for
      gamete fusion. It depends on an increase in [Ca(2+)](i) mediated by Ca(2+)
      channels. Although calmodulin (CaM) has been reported to regulate several events
      during the AR, it is not known whether it modulates sperm Ca(2+) channels. In the
      present study we analyzed the effects of CaM antagonists W7 and trifluoroperazine
      on voltage-dependent T-type Ca(2+) currents in mouse spermatogenic cells and on
      the zona pellucida-induced AR in sperm. We found that these CaM antagonists
      decreased T-currents in a concentration-dependent manner with IC(50) values of
      approximately 10 and approximately 12 microM, respectively. W7 altered the
      channels' voltage dependence of activation and slowed both activation and
      inactivation kinetics. It also induced inactivation at voltages at which T
      channels are not activated, suggesting a promotion of inactivation from the
      closed state. Consistent with this, W7 inhibited the ZP-induced [Ca(2+)](i)
      transients in capacitated sperm. Likewise, W7 and TFP inhibited the AR with an
      IC(50) of approximately 10 microM. In contrast, inhibitors of CaM-dependent
      kinase II and protein kinase A, as well as a CaM-activated phosphatase, had no
      effect either on T-currents in spermatogenic cells or on the sperm AR. Together
      these results suggest a functional interaction between CaM and the sperm T-type
      Ca(2+) channel. They are also consistent with the involvement of T-channels in
      the AR.

PMID- 11456456
TI  - A sustained increase in intracellular Ca(2+) is required for the acrosome
      reaction in sea urchin sperm.
AB  - The acrosome reaction (AR), necessary for fertilization in many species, requires
      an increase in intracellular Ca(2+) ([Ca(2+)](i)). In sea urchin sperm, the AR is
      triggered by an egg-jelly factor: the associated [Ca(2+)](i) elevation lasts
      minutes and involves two Ca(2+) permeable channels. Both the opening of the
      second channel and the onset of the AR occur approximately 5 s after treatment
      with egg factor, suggesting that these events are linked. In agreement, removal
      of Ca(2+) from sea water or addition of Ca(2+) channel blockers at the time when
      opening of the second channel is first detected inhibits AR and causes a "rapid"
      (t(1/2) = 3--15 s) decrease in [Ca(2+)](i) and partial inhibition of the
      intracellular pH change associated with the AR. Simultaneous addition of NH(4)Cl
      and either EGTA, Co(2+), or Ni(2+) 5 s after egg factor prevents the partial
      inhibition of the evoked pH(i) change observed but does not reverse AR
      inhibition. Therefore, the sustained increase in [Ca(2+)](i) caused by the second
      Ca(2+) channel is needed for the sperm AR. Experiments with agents that induce
      capacitative Ca(2+) uptake (thapsigargin and cyclopiazonic acid) suggest that the
      second channel opened during the AR could be a store-operated Ca(2+) channel.

PMID- 11456457
TI  - Regulation of the mRNAs encoding proteins of the BMP signaling pathway during the
      maternal stages of Xenopus development.
AB  - Activation of the Xenopus bone morphogenetic protein (BMP) pathway is coincident
      with the onset of zygotic transcription but requires maternal signaling proteins.
      The mechanisms controlling the translation of mRNAs that encode proteins of the
      BMP pathway were investigated by using polysome association as an assay for
      translational activity. Our results indicate that five different mRNAs encoding
      proteins of the BMP pathway were translationally regulated during Xenopus
      development. These mRNAs were either not associated or inefficiently associated
      with polysomes in oocytes, and each was recruited to polysomes at a different
      developmental stage. The Smad1 and ALK-2 mRNAs were recruited to polysomes during
      oocyte maturation, whereas the BMP-7 and XSTK9 mRNAs were recruited during the
      early stages of embryogenesis. The ALK-3 mRNA was not efficiently associated with
      polysomes during any maternal stage of development and was efficiently recruited
      to polysomes only after the onset of zygotic transcription. In general, for all
      stages except oocytes, polysome recruitment was associated with the presence of a
      3' poly(A) tail. However, there was not an obvious correlation between the
      absolute length of poly(A) and the efficiency of polysome recruitment, indicating
      that the relationship between poly(A) tail length and translation during early
      frog embryogenesis is complex. We further focused on the BMP-7 mRNA and
      demonstrated that sequence elements within the 3'UTR were necessary for
      recruitment of the BMP-7 mRNA to polysomes and sufficient to direct the addition
      of poly(A) and activate translation of a reporter during embryogenesis.
      Interestingly, the BMP-7 mRNA lacks the previously defined eCPE sequences
      proposed to direct poly(A) addition and translational activation during
      embryogenesis. The implications of our findings for translational regulation of
      maternal mRNAs during embryogenesis and for the activation of the BMP pathway are
      discussed.

PMID- 11456458
TI  - Calcium-mediated inactivation of the MAP kinase pathway in sea urchin eggs at
      fertilization.
AB  - We have evaluated the regulation of a 43-kDa MAP kinase in sea urchin eggs. Both
      MAP kinase and MEK (MAP kinase kinase) are phosphorylated and active in
      unfertilized eggs while both are dephosphorylated and inactivated after
      fertilization, although with distinct kinetics. Reactivation of MEK or the 43-kDa
      MAP kinase prior to or during the first cell division was not detected. Confocal
      immunolocalization microscopy revealed that phosphorylated (active) MAP kinase is
      present primarily in the nucleus of the unfertilized egg, with some of the
      phosphorylated form in the cytoplasm as well. Incubation of unfertilized eggs in
      the MEK inhibitor U0126 (0.5 microM) resulted in the inactivation of MEK and MAP
      kinase within 30 min. Incubation in low concentrations of U0126 (sufficient to
      inactivate MEK and MAP kinase) after fertilization had no effect on progression
      through the embryonic cell cycle. Microinjection of active mammalian MAP kinase
      phosphatase (MKP-3) resulted in inactivation of MAP kinase in unfertilized eggs,
      as did addition of MKP-3 to lysates of unfertilized eggs. Incubation of
      unfertilized eggs in the Ca(2+) ionophore A23187 led to inactivation of MEK and
      MAP kinase with the same kinetics as observed with sperm-induced egg activation.
      This suggests that calcium may be deactivating MEK and/or activating a MAP kinase
      directed phosphatase. A cell-free system was used to evaluate the activation of
      phosphatase separately from MEK inactivation. Unfertilized egg lysates were
      treated with U0126 to inactivate MEK and then Ca(2+) was added. This resulted in
      increased MAP kinase phosphatase activity. Therefore, MAP kinase inactivation at
      fertilization in sea urchin eggs likely is the result of a combination of MEK
      inactivation and phosphatase activation that are directly or indirectly
      responsive to Ca(2+).

PMID- 11456460
TI  - Epichloe festucae and related mutualistic symbionts of grasses.
AB  - Epichloe and Neotyphodium species (Ascomycota) are mutualistic symbionts
      (endophytes) of temperate grasses, to which they impart numerous and profound
      fitness benefits. Epichloe festucae, a common symbiont of Festuca, Lolium,and
      Koeleria spp., is a model for endophyte research that is amenable to Mendelian
      and molecular genetic analysis. Characteristics of E. festucae include: (i)
      production of the anti-insect alkaloids peramine and lolines, (ii) production of
      the anti-vertebrate alkaloids lolitrem B and ergovaline, (iii) efficient vertical
      transmission via host seeds, (iv) a mildly pathogenic state associated with the
      E. festucae sexual cycle, and (v) a clear role in enhancing survival of host
      plants. Genetic analysis of alkaloid production has recently begun. Also,
      physiological and ultrastructural studies suggest that signals communicated
      between E. festucae and host plants ensure an exquisitely balanced interaction to
      the mutual benefit of both partners. Several mutualistic Neotyphodium species are
      hybrids between E. festucae and other endophyte species.

PMID- 11456461
TI  - Intron mobility results in rearrangement in mitochondrial DNAs of heterokaryon
      incompatible Aspergillus japonicus strains after protoplast fusion.
AB  - Mitochondrial transmission was carried out under selective conditions between
      incompatible Aspergillus japonicus strains always using an oligomycin-resistant
      mitochondrial donor and selecting for recipient nuclei and oligomycin-resistant
      mitochondria. All attempted intraspecific mitochondrial transmissions were
      successful, but the transmission between closely related A. japonicus and A.
      aculeatus failed. Under selection pressure, resistant progeny harbor the
      mitochondrial DNA (mtDNA) of the donor strain, which may remain unchanged or may
      be modified by the introns of the recipient mitochondrial genome. Detailed
      analysis of a certain strain harboring rearranged mtDNA suggests that the mtDNA
      profiles of recombinant-like progeny are strongly influenced by the
      characteristics and mobility of introns of both parental mtDNAs. Both intron loss
      and intron acquisition play a role in the rearrangement of mtDNA. In certain
      parental combinations, a particular intron was lost very frequently.

PMID- 11456462
TI  - Botrytis cinerea endopolygalacturonase genes are differentially expressed in
      various plant tissues.
AB  - Botrytis cinerea, the causal agent of blight, rot, and gray mold on many plant
      species, secretes various endopolygalacturonases during all stages of infection.
      The expression pattern of the encoding genes (Bcpg 1-6) was studied on four
      hosts: tomato, broad bean, apple, and courgette (also known as zucchini). All
      gene family members are differentially expressed, depending on the stage of
      infection and the host. Bcpg1 is expressed in all tissues tested although
      differences in transcript levels occur. Bcpg2 expression is detected early in the
      infection of three of four plant tissues tested. Bcpg3 and Bcpg5 are expressed in
      apple fruit tissue, although probably as a result of different regulatory
      mechanisms. The expression patterns of Bcpg4 and 6 are in agreement with their
      inducibility by monogalacturonic acid. The pattern of Bcpg gene expression
      indicates that B. cinerea is equipped with a flexible enzymatic pectate
      degradation machinery. The studies pinpoint new targets for gene disruption
      studies.

PMID- 11456463
TI  - Monoclonal antibodies incorporated into Neotyphodium coenophialum fungal
      cultures: inhibition of fungal growth and stability of antibodies.
AB  - Three monoclonal antibodies (mAbs) produced against proteins from the tall fescue
      (Festuca arundinacea Schreb.) fungal endophyte Neotyphodium coenophialum
      hybridize exclusively to a fungal protein under denaturing conditions. The
      protein is approximately 88 kDa in size. These mAbs were individually
      incorporated into liquid medium to determine their effects on fungal growth in
      culture. Neotyphodium-specific mAbs inhibited fungal growth for the duration of
      the study. Fungal cultures grown in the presence of Neotyphodium-naive mAbs or in
      the absence of all mAbs grew unimpeded. Bright-field microscopy and
      immunohistochemical studies of cultures containing Neotyphodium-specific mAbs
      revealed a change in mycelia morphology with clumps exhibiting a gelatinous
      matrix containing sparse hyphae, while cultures receiving Neotyphodium-naive mAbs
      in medium demonstrated unrestricted growth with overlapping and branched hyphae.
      In liquid culture devoid of fungal isolates, mAbs were stable and detected
      throughout the experiment, but were below threshold detection levels within 15
      min following inclusion in liquid cultures containing Neotyphodium spp.,
      indicating rapid binding to fungal mycelia. Monoclonal antibodies may provide a
      new method to help control plant pathogenic fungi where chemical or genetic means
      are not feasible.

PMID- 11456464
TI  - Functional expression and cellular localization of a green fluorescent protein
      tagged proline transporter in Aspergillus nidulans.
AB  - The PrnB protein is a highly specific proline transporter that belongs to an
      amino acid transporter family conserved in both prokaryotes and eukaryotes. In
      this work, we detected and analyzed the cellular localization of PrnB in vivo by
      means of green fluorescent protein (GFP) fusions. Several prnB-gfp gene fusions,
      driven by prnB native promoter sequences, were constructed and targeted to the
      genomic locus of a prnB null mutant. Chimeric proteins containing GFP fused to
      the C terminus of PrnB through a linker of two, four, or eight amino acids, with
      low potential to form secondary structure elements, were shown to be functional
      in vivo. A two-linker fusion results in partial complementation at both 25 and 37
      degrees C. A four-linker fusion affords almost full complementation at 25 degrees
      C but partial complementation at 37 degrees C, whereas the eight-linker fusion
      results in partial complementation at both temperatures but in no GFP
      fluorescence. These results show that the number of linker amino acids is
      critical for the correct expression and/or translocation of PrnB-GFP fused
      proteins to the plasma membrane and for the fluorescence of the GFP. The
      expression of the four-linker PrnB-GFP transporter was detected and analyzed in
      vivo by both conventional fluorescence and confocal laser microscopy. This
      chimeric protein is localized in the plasma membrane, secondarily in large
      vacuoles found in the swollen conidial end of the germlings, and in other small
      intracellular structures observed as fluorescent granules. A strong correlation
      between known patterns of PrnB expression and intensity of PrnB-GFP fluorescence
      was observed. This work also demonstrates that the GFP fusion technology is a
      unique tool with which to study the expression and cellular localization of low
      abundance transmembrane transporters expressed from their native promoters.

PMID- 11456465
TI  - Identification of the gene at the pmg locus, encoding system II, the general
      amino acid transporter in Neurospora crassa.
AB  - Mutations at the pmg locus in Neurospora crassa cause a deficiency in a transport
      system for a broad range of amino acids. We have isolated a gene that encodes a
      protein with a high degree of sequence similarity to the GAP1 general amino acid
      permease in Saccharomyces cerevisiae. Our data indicate that this is the gene at
      the pmg locus. It encodes a 572-residue protein with a molecular mass of 62,649
      Da. The predicted secondary structure has 12 membrane-spanning regions, a feature
      characteristic of a superfamily of permease proteins. Inactivation of the gene
      yielded a mutant strain with the same phenotype as the pmg- strain, and a cosmid
      containing a functional copy of the gene rescued the pmg- strain. Although the
      pmg- strain has previously been assayed in a genetic background that contains
      mutations in genes for two other amino acid transport systems, we have found
      conditions in which the pmg- strain has an identifiable phenotype in an otherwise
      wild-type genetic background.

PMID- 11456466
TI  - Regions of microsynteny in Magnaporthe grisea and Neurospora crassa.
AB  - A bacterial artificial chromosome (BAC) clone containing 110,467 bp of genomic
      DNA from Magnaporthe grisea was sequenced, annotated, and compared to the genomes
      of Neurospora crassa, Candida albicans, and Saccharomyces cerevisiae. Twenty-six
      open reading frames (ORFs), involved in multiple biochemical pathways, were
      identified in the BAC sequence. A region of 53 kb, containing 18 of the 26 ORFs,
      was found to be syntenic to a portion of the N. crassa genome. Subregions of
      complete colinearity as well as interrupted colinearity were present. No synteny
      was evident with either C. albicans or S. cerevisiae. The identification of
      syntenic regions containing highly conserved genes across two genera that have
      been evolutionarily separated for approximately 200 million years elicits many
      biological questions as to the function and identity of these genes.

PMID- 11456467
TI  - Chemokines and their receptors in the central nervous system.
AB  - Chemokines are a family of proteins associated with the trafficking of leukocytes
      in physiological immune surveillance and inflammatory cell recruitment in host
      defence. They are classified into four classes based on the positions of key
      cystiene residues: C, CC, CXC, and CX3C. Chemokines act through both specific and
      shared receptors that all belong to the superfamily of G-protein-coupled
      receptors. Besides their well-established role in the immune system, several
      recent reports have demonstrated that these proteins also play a role in the
      central nervous system (CNS). In the CNS, chemokines are constitutively expressed
      by microglial cells, astrocytes, and neurons, and their expression can be
      increased after induction with inflammatory mediators. Constitutive expression of
      chemokines and chemokine receptors has been observed in both developing and adult
      brains, and the role played by these proteins in the normal brain is the object
      of intense study by many research groups. Chemokines are involved in brain
      development and in the maintenance of normal brain homeostasis; these proteins
      play a role in the migration, differentiation, and proliferation of glial and
      neuronal cells. The chemokine stromal cell-derived factor 1 and its receptor,
      CXCR4, are essential for life during development, and this ligand-receptor pair
      has been shown to have a fundamental role in neuron migration during cerebellar
      formation. Chemokine and chemokine receptor expression can be increased by
      inflammatory mediators, and this has in turn been associated with several acute
      and chronic inflammatory conditions. In the CNS, chemokines play an essential
      role in neuroinflammation as mediators of leukocyte infiltration. Their
      overexpression has been implicated in different neurological disorders, such as
      multiple sclerosis, trauma, stroke, Alzheimer's disease, tumor progression, and
      acquired immunodeficiency syndrome-associated dementia. An emerging area of
      interest for chemokine action is represented by the communication between the
      neuroendocrine and the immune system. Chemokines have hormone-like actions,
      specifically regulating the key host physiopathological responses of fever and
      appetite. It is now evident that chemokines and their receptors represent a
      plurifunctional family of proteins whose actions on the CNS are not restricted to
      neuroinflammation. These molecules constitute crucial regulators of cellular
      communication in physiological and developmental processes.

PMID- 11456468
TI  - DHEA and its transformation into androgens and estrogens in peripheral target
      tissues: intracrinology.
AB  - A new understanding of the endocrinology of menopause is that women, at
      menopause, are not only lacking estrogens resulting from cessation of ovarian
      activity but have also been progressively deprived for a few years of androgens
      and some estrogens originating from adrenal DHEA and androstenedione (4-dione).
      In fact, serum DHEA decreases by about 60% between the maximal levels seen at 30
      years of age to the age of menopause. This decreased secretion of DHEA and DHEA-S
      by the adrenals is responsible for a parallel decrease in androgen and estrogen
      formation in peripheral tissues by the steroidogenic enzymes specifically
      expressed in each cell type in individual target tissues. This new field of
      endocrinology, called intracrinology, describes the local synthesis of androgens
      and estrogens made locally in each cell of each peripheral tissue from the
      adrenal precursors DHEA and 4-dione. These androgens and estrogens exert their
      action in the same cells where their synthesis takes place and they are released
      from these target cells only after being inactivated. To further understand the
      effect of DHEA in women, DHEA has been administered in postmenopausal women for
      12 months. Such treatment resulted in increased bone formation and higher bone
      mineral density accompanied by elevated levels of osteocalcin, a marker of bone
      formation. Vaginal maturation was stimulated, while no effect was observed on the
      endometrium. Preclinical studies, on the other hand, have shown that, due to its
      predominant conversion into androgens, DHEA prevents the development and inhibits
      the growth of dimethylbenz(a)anthracene-induced mammary carcinoma in the rat, a
      model of breast cancer. DHEA also inhibits the growth of human breast cancer ZR
      75-1 xenografts in nude mice. The inhibitory effect of DHEA on breast cancer is
      due to an androgenic effect of testosterone and dihydrotestosterone made locally
      from DHEA. When used as replacement therapy, DHEA is free of the potential risk
      of breast and uterine cancer, while it stimulates bone formation and vaginal
      maturation and decreases insulin resistance. The combination of DHEA with a
      fourth generation SERM, such as EM-652 (SCH 57068), a compound having pure and
      potent antiestrogenic activity in the mammary gland and endometrium, could
      provide major benefits for women at menopause (inhibition of bone loss and serum
      cholesterol levels) with the associated major advantages of preventing breast and
      uterine cancer. A widely used application of intracrinology is the treatment of
      prostate cancer where the testicles are blocked by an LHRH agonist while the
      androgens made locally in the prostate from DHEA are blocked by a pure
      antiandrogen. Such treatment, called combined androgen blockade, has led to the
      first demonstration of a prolongation of life in prostate cancer.

PMID- 11456469
TI  - Growth hormone therapy in adults.
AB  - The importance of growth hormone (GH) deficiency in adults became evident 10 to
      15 years ago, when the first clinical studies on GH replacement therapy in adults
      were published. Since then, a number of studies have been reported showing that
      GH replacement therapy can improve this condition. Adult GH deficiency (GHD) is
      now recognized as a specific clinical syndrome and the first reports of long-term
      use of GH (up to 10 years) are now being published. The aim of this paper was to
      review the accumulated data on the various clinical aspects of adult GHD.

PMID- 11456470
TI  - The synthetic potential of phthalimide SET photochemistry.
AB  - The authors' studies in the area of phthalimide photochemistry are discussed in
      the context of the development of new methods for N-heterocycle synthesis.
      Emphasis is given to reactions which are initiated by both intermolecular and
      intramolecular SET from silicon-containing electron donors to excited states of
      phthalimides and related maleimides and conjugated imides. The photoaddition and
      photocyclization processes which ensue follow mechanistic pathways, in which
      efficient desilylation of initially formed radical cation occurs to generate
      radical pair and biradical intermediates that serve as precursors of the
      products. Several examples that demonstrate the preparative potential of these
      reactions are presented. These are taken from the authors' investigations of (1)
      phthalimido-alkylsilane photocyclization reactions, (2) azomethine ylide-forming
      excited-state processes of N-(trimethylsilylmethyl)phthalimide, and (3)
      photoaddition and photocyclization reactions of phthalimide alpha-silyl ether,
      thioether, amine, and amide systems.

PMID- 11456471
TI  - Reactions of electron-deficient alkynes and allenes under phosphine catalysis.
AB  - The development of some new synthetic reactions derived from nucleophilic
      addition of phosphines to electron-deficient carbon-carbon triple bonds is
      described. These reactions show that the phosphine plays the role of a
      nucleophile as well as an excellent leaving group. The central problem is to
      generate a 1,3-dipole from alkynoates or allenoates (2,3-butadienoates) by
      interaction with various phosphines. This study illuminates the unusual phenomena
      and shows how this understanding allows control of the reaction.

PMID- 11456472
TI  - Studies of polar stratospheric cloud formation.
AB  - Stratospheric ozone depletion was first reported in 1985. Early on, researchers
      identified polar stratospheric clouds (PSCs) as being important in chemistry
      related to ozone depletion. PSCs exist as crystalline water-ice particles (type
      II), and as crystalline (type Ia) or liquid (type Ib) particles stable above the
      water-ice frost point. Uncertainty remains concerning the composition and
      formation mechanism of the most common PSC, type Ia. Here, we consider likely
      formation mechanisms for type Ia PSCs.

PMID- 11456473
TI  - Photoisomerization by hula-twist: a fundamental supramolecular photochemical
      reaction.
AB  - The volume-conserving hula-twist cis/trans isomerization process has been
      incorporated in a general scheme for photoisomerization of polyenes, applicable
      to small organic molecules as well as to protein-bound polyene chromophores. The
      main theme is that in solution the conventional one-bond-flip mechanism
      dominates, while in frozen media (or under other forms of supramolecular
      constraint) the hula-twist mechanism takes over. Literature examples of
      photoisomerization obtained under confined conditions have been critically
      reviewed, the applicability of HT has been examined, and new systems
      unambiguously testing this volume-conserving process are proposed.

PMID- 11456474
TI  - Designer magnets containing cyanides and nitriles.
AB  - Magnets synthesized from molecules have contributed to the renaissance in the
      study of magnetic materials. Three-dimensional network solids exhibiting magnetic
      ordering have been made from several first-row metal ions and bridging
      unsaturated cyanide, tricyanomethanide, and/or dicyanamide ligands. These
      materials possess several different structural motifs, and the shorter the
      bridge, the stronger the interaction (i.e., -Ctriple bondN- > -Ntriple bondC-N-
      >> Ntriple bondC-N-Ctriple bondN- = Ntriple bondC-C-Ctriple bondN-). Cyanide
      additionally has the ability to discriminate between C- and N-bonding to form
      ordered heterobimetallic magnets, and the strong coupling can lead to ferro- or
      ferrimagnetic ordering substantially above room temperature. Tricoordination of
      tricyanomethanide results in spin-frustrated systems, which possess
      interpenetrating rutile-like networks. In contrast, single rutile-like frameworks
      are formed by mu(3)-bonded dicyanamide, which leads to ferromagnetics and weak
      ferromagnetics.

PMID- 11456475
TI  - The role of synchrotron-based studies in the elucidation and design of active
      sites in titanium-silica epoxidation catalysts.
AB  - X-ray absorption fine structure (XAFS) measurements unambiguously establish the
      structure of the active centers in high-performance Ti-SiO2 epoxidation
      catalysts. Subtleties in structural changes in proceeding from the dispersed
      titanocene dichloride precursor to the anchored Ti(IV) centers are charted, in
      situ, by both near-edge (XANES) and extended-edge (EXAFS) measurements. The
      active centers are tripodally attached titanol groups: (Si-O)3-TiOH. These permit
      facile expansion of the coordination shell (also monitored by in situ XAFS
      studies) during catalysis, and thereby lead to the formulation of a plausible
      mechanism of epoxidation of alkenes that is consonant with recent DFT
      computations. Previously proposed mechanisms, based on a three-coordinated
      titanyl group (as well as possible five- or six-coordinated active sites), are
      discounted. Comparable XAFS studies of soluble catalytically active four
      coordinated Ti(IV)-containing molecular entities establish that the heterogeneous
      Ti-SiO2 catalyst has "single-site" active centers. Equipped with such
      information, minute changes in hydrophobicity and local composition (e.g.,
      replacement of one Si by a Ge) can be wrought so as to boost the performance of
      the catalyst. The merits of using combined in situ X-ray absorption spectroscopic
      and X-ray diffractometric measurements are also highlighted.

PMID- 11456476
TI  - Structural elucidation of microporous and mesoporous catalysts and molecular
      sieves by high-resolution electron microscopy.
AB  - Twenty years ago, one of us embarked (Bursill, L. A.; Lodge, E. A.; Thomas, J. M.
      Zeolitic structures as revealed by high-resolution electron microscopy. Nature
      1980, 286, 111-113) on the study of zeolites (renowned for their electron-beam
      sensitivity) by high-resolution transmission electron microscopy (HRTEM). In the
      ensuing years, high-resolution imaging aided by optical diffractometry has
      yielded details of the open framework structures of a number of new
      aluminosilicate and aluminophosphate molecular sieves and catalysts. The nature
      of intergrowth and recurrently twinned structures, as well as new types of
      structural imperfection in hitherto uncharacterized materials, has also been
      elucidated. With continued improvements in instrumental development, encompassing
      higher accelerating voltages, better objective lenses and vacua, computational
      advances, and the arrival of slow-scan CCD detectors, electron crystallographic
      methods and HRTEM imaging now enable the ab initio three-dimensional structures
      of micro- and mesoporous solids, with their occluded structure-directing organic
      species, to be determined. High-resolution scanning transmission electron
      microscopy using subnanometric probes provides supplementary structural and
      ultramicro analytical information and electron spectroscopic imaging (at the
      attogram level). In its high-angle annular dark-field mode, it is capable of
      locating and determining the composition of individual nanoparticle catalysts
      (consisting of just a few atoms) supported on porous hosts.

PMID- 11456477
TI  - Exploration of fundamental and synthetic aspects of the intramolecular 4 + 3
      cycloaddition reaction.
AB  - In this Account, a summary of our work in the exploration and development of
      intramolecular 4 + 3 cycloaddition reactions between dienes and allylic cations
      is presented. Alkoxyallylic sulfones are useful precursors for the generation of
      allylic cations which are good dienophiles. Such substrates allowed a number of
      important pieces of data concerning the cycloaddition to be obtained. The
      evolution of the work has involved pursuing other methods for allylic cation
      generation, an investigation of stereochemical variables and applications,
      including the total syntheses of aphanamol I, widdrol, and (+)-dactylol.

PMID- 11456478
TI  - Why is it so difficult to simulate entropies, free energies, and their
      differences?
AB  - The classical 19th century thermodynamic inequalities of Clausius and Helmholtz
      are applied to the calculation of entropy and free energy changes by computer
      simulation. The irreversibility of finite-time thermodynamic paths is exploited
      to obtain upper and lower bounds on these quantities. Schrodinger's microscopic
      interpretation of heat and work provides the basis for a literal implementation
      of the key historical concepts on the computer using the Monte Carlo algorithm of
      Metropolis. Coupling schemes, paths, and reference states are variationally
      optimized to improve the convergence of the simulated properties, and a newly
      introduced variational flexibility, metric scaling, is overviewed. Reasons for
      expecting limiting power laws for the convergence are outlined.

PMID- 11456479
TI  - Participation of critical residues from the extreme C-terminal end of the human
      androgen receptor in the ligand binding function.
AB  - A short C-terminal end is present at the end of the human androgen receptor (hAR)
      similar to that of other steroid receptors. It is located directly after helix 12
      of the ligand binding domain and has never been described as being part of the
      hydrophobic binding pocket. Although some fragmentary data have indicated the
      involvement of this region in ligand binding, its precise function still remains
      unclear. To gain deeper insight into the role of the hAR extreme C-terminal end,
      an extensive mutational analysis was carried out by using site-directed
      mutagenesis and alanine scanning over the 13-residue C-terminal end region. Both
      ligand binding and transcriptional activity were tested with each mutant. Our
      study demonstrates the participation of almost all of the amino acids in this
      region for the ligand binding function and consequently for the transcriptional
      activity. A conformational study by limited proteolysis was performed with the
      mutants that most affected the affinity of the receptor. It was remarkable that
      the mutants with a low binding affinity adopted an inactive conformation and were
      either less or not able to undergo a following conformational change to provide
      the active form of the receptor. Our results demonstrate the importance of
      hydrophobicity for the function of the C-terminal end with residues located at
      very precise positions. Especially, both hydrophobicity and aromaticity on
      position 916 are critical for providing the correct ligand binding conformation
      of the receptor. Furthermore, this study highlights essential criteria regarding
      the C-terminal amino acids which could be applied to other steroid receptors.

PMID- 11456480
TI  - A ParE-ParC fusion protein is a functional topoisomerase.
AB  - Type II topoisomerases are responsible for DNA unlinking during DNA replication
      and chromosome segregation. Although eukaryotic enzymes are homodimers and
      prokaryotic enzymes are heterotetramers, both prokaryotic and eukaryotic type II
      topoisomerases belong to a single protein family. The amino- and carboxyl
      terminal domains of eukaryotic enzymes are homologous to the ATP-binding and
      catalytic subunits of prokaryotic enzymes, respectively. Topoisomerase IV, a
      prokaryotic type II topoisomerase, consists of the ATP-binding subunit, ParE, and
      the catalytic subunit, ParC. We have joined the coding regions of parE and parC
      in frame and constructed a fusion protein of the two subunits of topoisomerase
      IV. This fusion protein, ParEC, can catalyze both decatenation and relaxation
      reactions. The ParEC protein is also capable of decatenating replicating daughter
      DNA molecules during oriC DNA replication in vitro. Furthermore, the fusion gene,
      parEC, complements the temperature-sensitive growth of both parC and parE
      strains, indicating that the ParEC protein can substitute for topoisomerase IV in
      vivo. These results demonstrate that a fusion protein of the two subunits of
      topoisomerase IV is a functional topoisomerase. Thus, a heterotetrameric type II
      topoisomerase can be converted into a homodimeric type II topoisomerase by gene
      fusion.

PMID- 11456481
TI  - Stabilization factors affecting duplex formation of peptide nucleic acid with
      DNA.
AB  - Peptide nucleic acid (PNA) is an oligonucleotide analogue in which the sugar
      phosphate backbone is replaced by an N-(2-aminoethyl)glycine unit to which the
      nucleobases are attached. We investigated the thermodynamic behavior of PNA/DNA
      hybrid duplexes with identical nearest neighbors but with different sequences and
      chain lengths (5, 6, 7, 8, 10, 12, and 16 mers) to reveal whether the nearest
      neighbor model is valid for the PNA/DNA duplex stability. CD spectra of 6, 7, and
      8 mer PNA/DNA duplexes showed similar signal, while 10, 12, and 16 mer duplexes
      did not. The average difference in Delta G degrees (37) for short PNA/DNA
      duplexes with identical nearest-neighbor pairs was only 3.5%, whereas that of
      longer duplexes (10, 12, and 16 mers) was 16.4%. Therefore, the nearest-neighbor
      model seems to be useful at least for the short PNA/DNA duplexes. Thermodynamics
      of PNA/DNA duplexes containing 1--3 bulge residues were also studied. While the
      stability of the 12 mer DNA/DNA duplex decreased as the number of bulge bases
      increases, the number of bulge bases in PNA/DNA unchanged the duplex stability.
      Thus, the influence of bulge insertion in the PNA/DNA duplexes is different from
      that of a DNA/DNA duplex. This might be due to the different base geometry in a
      helix which may potentially make hydrogen bonds in a base pair and stacking
      interaction unfavorable compared with DNA/DNA duplexes.

PMID- 11456482
TI  - Interaction between cytochrome c2 and the photosynthetic reaction center from
      Rhodobacter sphaeroides: effects of charge-modifying mutations on binding and
      electron transfer.
AB  - The electrostatic interactions governing binding and electron transfer from
      cytochrome c(2) (cyt c(2)) to the reaction center (RC) from the photosynthetic
      bacteria Rhodobacter sphaeroides were studied by using site-directed mutagenesis
      to change the charges of residues on the RC surface. Charge-reversing mutations
      (acid --> Lys) decreased the binding affinity for cyt c(2). Dissociation
      constants, K(D) (0.3--250 microM), were largest for mutations of Asp M184 and
      nearby acid residues, identifying the main region for electrostatic interaction
      with cyt c(2). The second-order rate constants, k(2) (1--17 x 10(8) M(-1) s(-1)),
      increased with increasing binding affinity (log k(2) vs log 1/K(D) had a slope of
      approximately 0.4), indicating a transition state structurally related to the
      final complex. In contrast, first-order electron transfer rates, k(e), for the
      bound cyt did not change significantly (<3-fold), indicating that electron
      tunneling pathways were unchanged by mutation. Charge-neutralizing mutations
      (acid --> amide) showed changes in binding free energies of approximately 1/2 the
      free energy changes due to the corresponding charge-reversing mutations,
      suggesting that the charges in the docked complex remain well solvated. Charge
      enhancing mutations (amide --> acid) produced free energy changes of the same
      magnitude (but opposite sign) as changes due to the charge-neutralizing mutations
      in the same region, indicating a diffuse electrostatic potential due to cyt c(2).
      A two-domain model is proposed, consisting of an electrostatic docking domain
      with charged surfaces separated by a water layer and a hydrophobic tunneling
      domain with atomic contacts that provide an efficient pathway for electron
      transfer.

PMID- 11456483
TI  - Platination of the (T2G4)4 telomeric sequence: a structural and cross-linking
      study.
AB  - The telomeric sequence (T(2)G(4))(4) was platinated in aqueous solutions
      containing 50 mM LiClO(4), NaClO(4), or KClO(4). The identification of the
      guanines which reacted with [Pt(NH(3))(3)(H(2)O)](2+) revealed that the same type
      of folding exists in the presence of the three cations and that the latter
      determine the relative stabilities of the G-quadruplex structures in the order
      K(+) > Na(+) >> Li(+). The tri-ammine complex yielded ca. 40--90% of adducts,
      mono- and poly-platinated, bound to 4 guanines out of the 16 guanines in the
      sequence, in the decreasing amounts G9 > G15 >> G3 > G21. The formation of these
      adducts was interpreted with a G-quadruplex structure obtained by restrained
      molecular dynamics (rMD) simulations which confirms the schematic model proposed
      by Williamson et al. [(1989) Cell 59, 871--880]. The bifunctional complexes cis-
      and trans-[Pt(NH(3))(2)(H(2)O)(2)](2+) also first reacted with G9 and G15 and
      gave cross-linked adducts between two guanines, which did not exceed 5% each of
      the products formed. Both the cis and trans isomers formed a G3-G15 platinum
      chelate, and the second also formed bis-chelates at both ends of the G-quadruplex
      structure: G3-G15/G9-G21 and G3-G15/G9-G24. The rMD simulations showed that the
      cross-linking reactions by the trans complex can occur without disturbing the
      stacking of the three G-quartets.

PMID- 11456484
TI  - Solution structure of the dimeric cytoplasmic domain of syndecan-4.
AB  - The syndecans, transmembrane proteoglycans which are involved in the organization
      of cytoskeleton and/or actin microfilaments, have important roles as cell surface
      receptors during cell-cell and/or cell-matrix interactions. Since previous
      studies indicate that the function of the syndecan-4 cytoplasmic domain is
      dependent on its oligomeric status, the conformation of the syndecan-4
      cytoplasmic domain itself is important in the understanding of its biological
      roles. Gel filtration results show that the syndecan-4 cytoplasmic domain (4L)
      itself forms a dimer stabilized by ionic interactions between peptides at
      physiological pH. Commensurately, the NMR structures demonstrate that syndecan-4L
      is a compact intertwined dimer with a symmetric clamp shape in the central
      variable V region with a root-mean-square deviation between backbone atom
      coordinates of 0.95 A for residues Leu(186)-Ala(195). The molecular surface of
      the 4L dimer is highly positively charged. In addition, no intersubunit NOEs in
      membrane proximal amino acid resides (C1 region) have been observed,
      demonstrating that the C1 region is mostly unstructured in the syndecan-4L dimer.
      Interestingly, two parallel strands of 4L form a cavity in the center of the
      dimeric twist similar to our previously reported 4V structure. The overall
      topology of the central variable region within the 4L structure is very similar
      to that of 4V complexed with the phosphatidylinositol 4,5-bisphosphate; however,
      the intersubunit interaction mode is affected by the presence of C1 and C2
      regions. Therefore, we propose that although the 4V region in the full
      cytoplasmic domain has a tendency for strong peptide--peptide interaction, it may
      not be enough to overcome the repulsion of the C1 regions of syndecan-4L.

PMID- 11456485
TI  - Phosphorylation of RNA polymerase II CTD fragments results in tight binding to
      the WW domain from the yeast prolyl isomerase Ess1.
AB  - The yeast prolyl isomerase, Ess1, has recently been shown to interact via its WW
      domain with the hyperphosphorylated form of the RNA polymerase II C-terminal
      domain (CTD). We have investigated folding of the Ess1 WW domain and its binding
      to peptides representing the CTD by circular dichroism and fluorescence. Ess1 WW
      folds and unfolds reversibly, but in the absence of ligand is only marginally
      stable with a melting temperature of 19 degrees C. The WW domain is stabilized by
      the addition of anionic ligands, namely, chloride, inorganic phosphate,
      phosphoserine, and phosphorylated CTD peptides. Dissociation constants were
      measured to be 70--100 microM for CTD peptides phosphorylated at one serine, and
      16--21 microM for peptides with two or more phosphorylated serines. Weaker or no
      affinity was observed for nonphosphorylated CTD peptides. There is surprisingly
      little difference in the affinity for peptides phosphorylated at Ser 2 or Ser 5
      of the consensus repeat, or for peptides with different patterns of multiple
      phosphorylation. The binding of Ess1 to phosphorylated CTD peptides is consistent
      with a model wherein the WW domain positions Ess1 to catalyze isomerization of
      the many pSer--Pro peptide bonds in the phosphorylated CTD. We suggest that
      cis/trans isomerization of prolyl peptide bonds plays a crucial role in CTD
      function during eukaryotic transcription.

PMID- 11456486
TI  - Structure-function analysis of a phage display-derived peptide that binds to
      insulin-like growth factor binding protein 1.
AB  - Highly structured, peptide antagonists of the interaction between insulin-like
      growth factor 1 (IGF-I) and IGF binding protein 1 (IGFBP-1) have recently been
      discovered by phage display of naive peptide libraries [Lowman, H. B., et al.
      (1998) Biochemistry 37, 8870--8878]. We now report a detailed analysis of the
      features of this turn-helix peptide motif that are necessary for IGFBP-1 binding
      and structural integrity. Further rounds of phage randomization indicate the
      importance of residues contributing to a hydrophobic patch on one face of the
      helix. Alanine-scanning substitutions confirm that the hydrophobic residues are
      necessary for binding. However, structural analysis by NMR spectroscopy indicates
      that some of these analogues are less well folded. Structured, high-affinity
      analogues that lack the disulfide bond were prepared by introducing a covalent
      constraint between side chains at positions i and i + 7 or i + 8 within the
      helix. Analogues based on this scaffold demonstrate that a helical conformation
      is present in the bound state, and that hydrophobic side chains in this helix,
      and residues immediately preceding it, interact with IGFBP-1. By comparison of
      alanine scanning data for IGF-I and the turn-helix peptide, we propose a model
      for common surface features of these molecules that recognize IGFBP-1.

PMID- 11456487
TI  - Apolipoprotein E inhibits the depolymerization of beta 2-microglobulin-related
      amyloid fibrils at a neutral pH.
AB  - beta 2-Microglobulin-related (A beta 2M) amyloidosis is a common and serious
      complication in patients on long-term hemodialysis, and beta 2-microglobulin
      (beta 2-m) is a major structural component of A beta 2M amyloid fibrils.
      Fluorescence spectroscopic analysis with thioflavin T and electron microscopic
      study revealed that A beta 2M amyloid fibrils readily depolymerize into monomeric
      beta 2-m at a neutral to basic pH. Circular dichroism analysis revealed that soon
      after the initiation of the depolymerization reaction at pH 7.5, the
      characteristic spectrum of beta 2-m in A beta 2M amyloid fibrils changes to
      resemble that of monomeric beta 2-m at pH 7.5. Apolipoprotein E (apoE), a
      representative amyloid-associated protein, formed a stable complex with A beta 2M
      amyloid fibrils and inhibited the depolymerization of A beta 2M amyloid fibrils
      dose-dependently in a range of 0--10 microM. These results showed that apoE could
      enhance the deposition of amyloid fibrils in vivo, possibly by binding directly
      to the surface of the fibrils and stabilizing the conformation of beta 2-m in the
      fibrils.

PMID- 11456488
TI  - Anticoagulant activities of a monoclonal antibody that binds to exosite II of
      thrombin.
AB  - A monoclonal IgG isolated from a patient with multiple myeloma has been shown to
      bind to exosite II of thrombin, prolong both the thrombin time and the activated
      partial thromboplastin time (aPTT) when added to normal plasma, and alter the
      kinetics of hydrolysis of synthetic peptide substrates. Although the IgG does not
      affect cleavage of fibrinogen by thrombin, it increases the rate of inhibition of
      thrombin by purified antithrombin approximately 3-fold. Experiments with plasma
      immunodepleted of antithrombin or heparin cofactor II confirm that prolongation
      of the thrombin time requires antithrombin. By contrast, prolongation of the aPTT
      requires neither antithrombin nor heparin cofactor II. The IgG delays clotting of
      plasma initiated by purified factor IXa but has much less of an effect on
      clotting initiated by factor Xa. In a purified system, the IgG decreases the rate
      of activation of factor VIII by thrombin. These studies indicate that binding of
      a monoclonal IgG to exosite II prolongs the thrombin time indirectly by
      accelerating the thrombin-antithrombin reaction and may prolong the aPTT by
      interfering with activation of factor VIII, thereby diminishing the catalytic
      activity of the factor IXa/VIIIa complex.

PMID- 11456489
TI  - The staphylococcal leukocidin bicomponent toxin forms large ionic channels.
AB  - The genes encoding the F and S components of a leukocidin, LukF (HlgB) and LukS
      (HlgC), a pore-forming binary toxin, were amplified from the Smith 5R strain of
      Staphylococcus aureus both with and without sequences encoding 3'-hexahistidine
      tags. The His-tagged components were expressed in Escherichia coli and purified
      under nondenaturing conditions. In addition, the two unmodified proteins and the
      His-tagged versions were produced in an E. coli cell-free in vitro transcription
      and translation system. An SDS-stable oligomer of approximately 200 kDa appeared
      when both components were cotranslated in the presence of rabbit erythrocyte
      membranes. Hemolytic activity of the combined components against rabbit
      erythrocytes was measured for both in vitro- and in vivo-produced polypeptides,
      yielding similar HC(50) values of approximately 0.14 microg/mL. The pore-forming
      properties of the recombinant leukocidin were also investigated with planar lipid
      bilayers of diphytanoylphosphatidylcholine. Although leukocidins and
      staphylococcal alpha-hemolysin share partial sequence identity and related folds,
      LukF and LukS produce a pore with a unitary conductance of 2.5 nS [1 M KCl and 5
      mM HEPES (pH 7.4)], which is more than 3 times greater than that of alpha
      hemolysin measured under the same conditions. Therefore, if the leukocidin pore
      were a cylinder, its diameter would be almost twice that of alpha-hemolysin. In
      addition, the leukocidin pore is weakly cation selective and exhibits gating at
      low positive potentials, while alpha-hemolysin is weakly anion selective and
      gates only at high potentials. Taken together, these data suggest that the
      structure of the oligomeric pore formed by the leukocidin examined here has
      diverged significantly from that of alpha-hemolysin.

PMID- 11456490
TI  - Inactivation of C30A trimethylamine dehydrogenase by N-cyclopropyl-alpha
      methylbenzylamine, 1-phenylcyclopropylamine, and phenylhydrazine.
AB  - Trimethylamine dehydrogenase (TMADH) from the bacterium Methylophilus
      methylotrophus (sp. W(3)A(1)) and its C30A mutant were inactivated with three
      known inactivators of monoamine oxidase, namely, phenylhydrazine, N-cyclopropyl
      alpha-methylbenzylamine, and 1-phenylcyclopropylamine. All three compounds
      irreversibly inactivated both the wild-type and C30A mutant enzymes, although
      phenylhydrazine was 10 times more potent than N-cyclopropyl-alpha
      methylbenzylamine, which was much more potent than 1-phenylcyclopropylamine. The
      change in the UV--visible absorption spectra upon modification indicated that the
      flavin was modified. In the case of the C30A mutant, the absence of a covalent
      attachment of the flavin to the polypeptide has permitted LC-electrospray mass
      spectrometry of the reaction product to be undertaken, demonstrating new mass
      peaks corresponding to various chemically modified forms of the flavin cofactor.
      In the case of N-cyclopropyl-alpha-methylbenzylamine, masses corresponding to
      hydroxy-FMN and hydroxyriboflavin were detected. 1-Phenylcyclopropylamine
      inactivation of the C30A mutant produced three modified flavins, as evidenced by
      the electrospray mass spectrum: hydroxy-FMN, FMN plus C(6)H(5)COCH(2)CH(2), and
      hydroxy-FMN plus C(6)H(5)COCH(2)CH(2). Phenylhydrazine inactivation of the C30A
      mutant gave at least seven different modified flavins: hydroxyriboflavin, hydroxy
      FMN, two apparently isomeric compounds corresponding to hydroxy-FMN plus one
      phenyl group, two apparently isomeric compounds corresponding to FMN plus one
      phenyl group, and FMN plus two phenyl groups. Covalent flavin adduct formation
      appears to be the only modification because dialysis of the inactive enzyme
      followed by reconstitution with FMN restores the enzyme activity to that of a
      noninactivated control.

PMID- 11456491
TI  - Elongation factor Ts can act as a steric chaperone by increasing the solubility
      of nucleotide binding-impaired elongation factor-Tu.
AB  - Several elongation factor (EF) Tu mutants (T25A, H22Y/T25S, D80N, D138N) that
      have impaired nucleotide binding show decreased solubility on overexpression in
      the E. coli cell, an indication that they do not fold correctly. Moreover, EF
      Tu[T25A] and EF-Tu[D80N] were shown to inhibit cell growth on expression, an
      effect attributed to their sequestration of EF-Ts [Krab, I. M., and Parmeggiani,
      A. (1999) J. Biol. Chem. 274, 11132--11138; Krab, I. M., and Parmeggiani, A.
      (1999) Biochemistry 38, 13035--13041]. We present here results showing that the
      co-overexpression of EF-Ts at a 1:1 ratio dramatically improves the solubility of
      mutant EF-Tu, although in the case of EF-Tu[D138N]--which cannot at all bind the
      nucleotides available in the cell--this is a slow process. Moreover, with co
      overexpression of EF-Ts, the mentioned growth inhibition is relieved. We conclude
      that for the formation of a correct EF-Tu structure the nucleotide plays an
      important role as a "folding nucleus", and also that in its absence EF-Ts can act
      as a folding template or steric chaperone for the correct folding of EF-Tu.

PMID- 11456492
TI  - Effect of mutation of proline 93 on redox unfolding/folding of bovine pancreatic
      ribonuclease A.
AB  - Both the reductive unfolding and oxidative regeneration of a P93A mutant and wild
      type RNase A have been studied at 15 degrees C and pH 8.0. The rate of reduction
      of the 40--95 disulfide bond is accelerated about 120-fold by the P93A mutation,
      while the reduction of the 65--72 disulfide bond is not accelerated by this
      mutation (within the experimental error). Moreover, the reduction of native P93A
      to des[40--95] is about 10 times faster than the further reduction of the same
      des[40--95] species. These results demonstrate that the reduction of the mutant
      proceeds through a local unfolding event and provides strong support for our
      model in which the reduction of wild-type RNase A to the des species proceeds
      through two independent local conformational unfolding events. The oxidative
      regeneration rate of the P93A mutant is comparable to that of wild-type RNase A,
      suggesting that a cis 92--93 peptide group that is present in native wild-type
      RNase A and in native des[40--95], is not obligatory for the formation of the
      third (final) native disulfide bond of des[40--95] by reshuffling from an
      unstructured 3S precursor. Thus, the trans to cis isomerization of the Tyr92
      Pro93 peptide group during the regeneration of wild-type RNase A may occur after
      the formation of the third native disulfide bond.

PMID- 11456493
TI  - Intramolecular electron transfer from c heme to d1 heme in bacterial cytochrome
      cd1 nitrite reductase occurs over the same distances at very different rates
      depending on the source of the enzyme.
AB  - Intramolecular electron transfer over 12 A from heme c to heme d(1) was
      investigated in cytochrome cd(1) nitrite reductase from Pseudomonas aeruginosa,
      following reduction of the c heme by pulse radiolysis. The rate constant for the
      transfer is relatively slow, k = 3 s(-1). The present observations contrast with
      a corresponding rate of electron transfer, 1.4 x 10(3) s(-1), measured for
      cytochrome cd(1) from Paracoccus pantotrophus, though the relative positions of
      the two heme groups are the same in both enzymes. The rate of intramolecular
      electron transfer within the enzyme from P. aeruginosa was accelerated 10(4)-fold
      (1.4 x 10(4) s(-1)) by the binding of cyanide to the d(1) heme. A coordination
      change at the d(1) heme upon its reduction is suggested to be a major factor in
      determining the slow rate of electron transfer in the P. aeruginosa enzyme in the
      absence of cyanide.

PMID- 11456494
TI  - Site-directed mutation of the highly conserved region near the Q-loop of the
      cytochrome bd quinol oxidase from Escherichia coli specifically perturbs heme
      b595.
AB  - Cytochrome bd is one of the two quinol oxidases in the respiratory chain of
      Escherichia coli. The enzyme contains three heme prosthetic groups. The dioxygen
      binding site is heme d, which is thought to be part of the heme-heme binuclear
      center along with heme b(595), which is a high-spin heme whose function is not
      known. Protein sequence alignments [Osborne, J. P., and Gennis, R. B. (1999)
      Biochim. Biophys Acta 1410, 32--50] of cytochrome bd quinol oxidase sequences
      from different microorganisms have revealed a highly conserved sequence
      (GWXXXEXGRQPW; bold letters indicate strictly conserved residues) predicted to be
      on the periplasmic side of the membrane between transmembrane helices 8 and 9 in
      subunit I. The functional importance of this region is investigated in the
      current work by site-directed mutagenesis. Several mutations in this region
      (W441A, E445A/Q, R448A, Q449A, and W451A) resulted in a catalytically inactive
      enzyme with abnormal UV--vis spectra. E445A was selected for detailed analysis
      because of the absence of the absorption bands from heme b(595). Detailed
      spectroscopic and chemical analyses, indeed, show that one of the three heme
      prosthetic groups in the enzyme, heme b(595), is specifically perturbed and
      mostly missing from this mutant. Surprisingly, heme d, while known to interact
      with heme b(595), appears relatively unperturbed, whereas the low-spin heme
      b(558) shows some modification. This is the first report of a mutation that
      specifically affects the binding site of heme b(595).

PMID- 11456495
TI  - Human RAD52 protein has extreme thermal stability.
AB  - The human RAD52 protein plays an important role in the earliest stages of
      chromosomal double-strand break repair via the homologous recombination pathway.
      Individual subunits of RAD52 associate into seven-membered rings. These rings can
      form higher order complexes. RAD52 binds to DNA breaks, and recent studies
      suggest that the higher order self-association of the rings promotes DNA end
      joining. Monomers of the RAD52(1--192) deletion mutant also associate into ring
      structures but do not form higher order complexes. The thermal stability of wild
      type and mutant RAD52 was studied by differential scanning calorimetry. Three
      thermal transitions (labeled A, B, and C) were observed with melting temperatures
      of 38.8, 73.1, and 115.2 degrees C. The RAD52(1--192) mutant had only two thermal
      transitions at 47.6 and 100.9 degrees C (labeled B and C). Transitions were
      labeled such that transition C corresponds to complete unfolding of the protein.
      The effect of temperature and protein concentration on RAD52 self-association was
      analyzed by dynamic light scattering. From these data a four-state hypothetical
      model was developed to explain the thermal denaturation profile of wild-type
      RAD52. The three thermal transitions in this model were assigned as follows.
      Transition A was attributed to the disruption of higher order assemblies of RAD52
      rings, transition B to the disruption of rings to individual subunits, and
      transition C to complete unfolding. The ring-shaped quaternary structure of RAD52
      and the formation of higher ordered complexes of rings appear to contribute to
      the extreme stability of RAD52. Higher ordered complexes of rings are stable at
      physiological temperatures in vitro.

PMID- 11456496
TI  - Profile of changes in lipid bilayer structure caused by beta-amyloid peptide.
AB  - beta-Amyloid peptide (A beta) is the primary constituent of senile plaques, a
      defining feature of Alzheimer's disease. Aggregated A beta is toxic to neurons,
      but the mechanism of toxicity is uncertain. One hypothesis is that interactions
      between A beta aggregates and cell membranes mediate A beta toxicity. Previously,
      we described a positive correlation between the A beta aggregation state and
      surface hydrophobicity, and the ability of the peptide to decrease fluidity in
      the center of the membrane bilayer [Kremer, J. J., et al. (2000) Biochemistry 39,
      10309--10318]. In this work, we report that A beta aggregates increased the
      steady-state anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) embedded in the
      hydrophobic center of the membrane in phospholipids with anionic, cationic, and
      zwitterionic headgroups, suggesting that specific charge--charge interactions are
      not required for A beta--membrane interactions. A beta did not affect the
      fluorescence lifetime of DPH, indicating that the increase in anisotropy is due
      to increased ordering of the phospholipid acyl chains rather than changes in
      water penetration into the bilayer interior. A beta aggregates affected membrane
      fluidity above, but not below, the lipid phase-transition temperature and did not
      alter the temperature or enthalpy of the phospholipid phase transition. A beta
      induced little to no change in membrane structure or water penetration near the
      bilayer surface. Overall, these results suggest that exposed hydrophobic patches
      on the A beta aggregates interact with the hydrophobic core of the lipid bilayer,
      leading to a reduction in membrane fluidity. Decreases in membrane fluidity could
      hamper functioning of cell surface receptors and ion channel proteins; such
      decreases have been associated with cellular toxicity.

PMID- 11456497
TI  - Oligomerization of NHERF-1 and NHERF-2 PDZ domains: differential regulation by
      association with receptor carboxyl-termini and by phosphorylation.
AB  - PDZ domains bind to the carboxyl-termini of target proteins, and some PDZ domains
      are capable of oligomerization to facilitate the formation of intracellular
      signaling complexes. The Na(+)/H(+) exchanger regulatory factor (NHERF-1; also
      called "EBP50") and its relative NHERF-2 (also called "E3KARP", "SIP-1", and "TKA
      1") both have two PDZ domains. We report here that the PDZ domains of NHERF-1 and
      NHERF-2 bind specifically to each other but not to other PDZ domains. Purified
      NHERF-2 PDZ domains associate with each other robustly in the absence of any
      associated proteins, but purified NHERF-1 PDZ domains associate with each other
      only weakly when examined alone. The oligomerization of the NHERF-1 PDZ domains
      is greatly facilitated when they are bound with carboxyl-terminal ligands, such
      as the carboxyl-termini of the beta(2)-adrenergic receptor or the platelet
      derived growth factor receptor. Oligomerization of full-length NHERF-1 is also
      enhanced by mutation of serine 289 to aspartate (S289D), which mimics the
      phosphorylated form of NHERF-1. Co-immunoprecipitation experiments with
      differentially tagged versions of the NHERF proteins reveal that NHERF-1 and
      NHERF-2 form homo- and hetero-oligomers in a cellular context. A point-mutated
      version of NHERF-1 (S289A), which cannot be phosphorylated on serine 289,
      exhibits a reduced capacity for co-immunoprecipitation from cells. These studies
      reveal that both NHERF-1 and NHERF-2 can oligomerize, which may facilitate NHERF
      mediated formation of cellular signaling complexes. These studies furthermore
      reveal that oligomerization of NHERF-1, but not NHERF-2, is highly regulated by
      association with other proteins and by phosphorylation.

PMID- 11456498
TI  - High-affinity binding of a FYVE domain to phosphatidylinositol 3-phosphate
      requires intact phospholipid but not FYVE domain oligomerization.
AB  - FYVE domains are small zinc-finger-like domains found in many proteins that are
      involved in regulating membrane traffic and have been shown to bind specifically
      to phosphatidylinositol 3-phosphate (PtdIns-3-P). FYVE domains are thought to
      recruit PtdIns-3-P effectors to endosomal locations in vivo, where these
      effectors participate in controlling endosomal maturation and vacuolar protein
      sorting. We have compared the characteristics of PtdIns-3-P binding by the FYVE
      domain from Hrs-1 (the hepatocyte growth factor-regulated tyrosine kinase
      substrate) with those of specific phosphoinositide binding by Pleckstrin homology
      (PH) domains. Like certain PH domains (such as that from phospholipase C
      delta(1)), the Hrs-1 FYVE domain specifically recognizes a single
      phosphoinositide. However, while phosphoinositide binding by highly specific PH
      domains is driven almost exclusively by interactions with the lipid headgroup,
      this is not true for the Hrs-1 FYVE domain. The phospholipase C-delta(1) PH
      domain shows a 10-fold preference for binding isolated headgroup over its
      preferred lipid (phosphatidylinositol 4,5-bisphosphate) in a membrane, while the
      Hrs-1 FYVE domain greatly prefers (more than 50-fold) intact lipid in a bilayer
      over the isolated headgroup (inositol 1,3-bisphosphate). By contrast with reports
      for certain PH domains, we find that this preference for membrane binding over
      interaction with soluble lipid headgroups does not require FYVE domain
      oligomerization.

PMID- 11456499
TI  - 19F NMR of trifluoroacetyl-labeled cysteine mutants of myoglobin: structural
      probes of nitric oxide bound to the H93G cavity mutant.
AB  - Nitric oxide (NO) binds to the myoglobin (Mb) cavity mutant, H93G, forming either
      a 5- or 6-coordinate Fe--NO heme complex. The H93G mutation replaces the proximal
      histidine of Mb with glycine, allowing exogenous ligands to occupy the proximal
      binding site. In the absence of the covalently attached proximal ligand, NO could
      bind to H93G from the proximal side of the heme rather than the typical diatomic
      binding pocket on the distal side when the 5-coordinate complex forms. The
      question of whether NO binds on the distal or proximal side was addressed by
      (19)F NMR. Site-directed mutagenesis was used to introduce unique cysteine
      residues at the protein surface on either the distal (S58C) or proximal (L149C)
      side, approximately equidistant from and perpendicular to the heme plane of both
      wild-type and H93G Mb. The cysteine thiols were alkylated with 3-bromo-1,1,1
      trifluoroacetone to attach a trifluoroacetyl group at the mutation site. (19)F
      NMR spectra of 5-coordinate, NO bound S58C/H93G and L149C/H93G double mutants
      depict peaks with line widths of 100 and 23 Hz, respectively. As fluorine peaks
      broaden with increasing proximity to paramagnetic centers, such as 5-coordinate
      Fe--NO, the (19)F NMR data are consistent with NO binding in the distal heme
      pocket of H93G, even in the absence of a sixth axial ligand. Additionally, (19)F
      NMR spectra are reported for deoxy, oxy, CO, met CN, and met H(2)O forms of the
      labeled cysteine mutants. These results demonstrate that the fluorine probes are
      sensitive to subtle conformational changes in the protein structure due to
      ligation and oxidation state changes of the heme iron in Mb.

PMID- 11456500
TI  - Active site characteristics of CYP4B1 probed with aromatic ligands.
AB  - The active site topography of rabbit CYP4B1 has been studied relative to CYP2B1
      and CYP102 using a variety of aromatic probe substrates. Oxidation of the
      prochiral substrate cumene by CYP4B1, but not CYP2B1 or CYP102, resulted in the
      formation of the thermodynamically disfavored omega-hydroxy metabolite, 2-phenyl
      1-propanol, with product stereoselectivity for the (S)-enantiomer. Reaction of
      CYP4B1, CYP2B1, and CYP102 with phenyldiazene produced spectroscopically
      observable sigma-complexes for each enzyme. Subsequent oxidation of the CYP2B1
      and CYP102 complexes followed by LC/ESI--MS analysis yielded heme pyrrole
      migration patterns similar to those in previous literature reports. Upon
      identical treatment, no migration products were detected for CYP4B1.
      Intramolecular deuterium isotope effects for the benzylic hydroxylation of o
      xylene-alpha-(2)H(3), p-xylene-alpha-(2)H(3), 2-(2)H(3),6-dimethylnaphthalene,
      and 4-(2)H(3),4'-dimethylbiphenyl were determined for CYP4B1 and CYP2B1 to
      further map their active site dimensions. These probes permit assessment of the
      ease of equilibration, within P450 active sites, of oxidizable methyl groups
      located between 3 and 10 A apart [Iyer et al. (1997) Biochemistry 36, 7136-
      7143]. Isotope effects for the CYP4B1-mediated benzylic hydroxylation of o- and p
      xylenes were fully expressed (k(H)/k(D) = 9.7 and 6.8, respectively), whereas
      deuterium isotope effects for the naphthyl and biphenyl derivatives were both
      substantially masked (k(H)/k(D) approximately equal to 1). In contrast,
      significant suppression of the deuterium isotope effects for CYP2B1 occurred only
      with the biphenyl substrate. Therefore, rapid equilibration between two methyl
      groups more than 6 A apart is impeded within the active site of CYP4B1, whereas
      for CYP2B1, equilibration is facile for methyl groups distanced by more than 8 A.
      Collectively, all data are consistent with the conclusion that the active site of
      CYP4B1 is considerably restricted relative to CYP2B1.

PMID- 11456503
TI  - Metal ion inhibition of nonenzymatic pyridoxal phosphate catalyzed
      decarboxylation and transamination.
AB  - Nonenzymatic pyridoxal phosphate (PLP) catalyzed decarboxylations and
      transaminations have been revisited experimentally. Metal ions are known to
      catalyze a variety of PLP-dependent reactions in solution, including
      transamination. It is demonstrated here that the rate accelerations previously
      observed are due solely to enhancement of Schiff base formation under
      subsaturating conditions. A variety of metal ions were tested for their effects
      on the reactivity of the 2-methyl-2-aminomalonate Schiff bases. All were found to
      have either no effect or a small inhibitory one. The effects of Al(3+) were
      studied in detail with the Schiff bases of 2-methyl-2-aminomalonate, 2
      aminoisobutyrate, alanine, and ethylamine. The decarboxylation of 2-methyl-2
      aminomalonate is unaffected by metalation with Al(3+), while the decarboxylation
      of 2-aminoisobutyrate is inhibited 125-fold. The transamination reaction of
      ethylamine is 75-fold slower than that of alanine. Ethylamine transamination is
      inhibited 4-fold by Al(3+) metalation, while alanine transamination is inhibited
      only 1.3-fold. Metal ion inhibition of Schiff base reactivity suggests a simple
      explanation for the lack of known PLP dependent enzymes that make direct
      mechanistic use of metal ions. A comparison of enzyme catalyzed, PLP catalyzed,
      and uncatalyzed reactions shows that PLP dependent decarboxylases are among the
      best known biological rate enhancers: decarboxylation occurs 10(18)-fold faster
      on the enzyme surface than it does free in solution. PLP itself provides the
      lion's share of the catalytic efficiency of the holoenzyme: at pH 8, free PLP
      catalyzes 2-aminoisobutyrate decarboxylation by approximately 10(10)-fold, with
      the enzyme contributing an additional approximately 10(8)-fold.

PMID- 11456504
TI  - Lithium diisopropylamide: oligomer structures at low ligand concentrations.
AB  - One- and two-dimensional (6)Li and (15)N NMR spectroscopic studies of lithium
      diisopropylamide (LDA) solvated by substoichiometric concentrations of oxetane,
      THF, Et(2)O, and diisopropylamine are described. Partially solvated dimers and
      trimers are identified. Possible benefits of carrying out organolithium chemistry
      at low ligand concentrations are discussed.

PMID- 11456505
TI  - Nonstoichiometric La(2 - x)GeO(5 - delta) monoclinic oxide as a new fast oxide
      ion conductor.
AB  - Oxide ion conductivity in La(2)GeO(5)-based oxide was investigated and it was
      found that La-deficient La(2)GeO(5) exhibits oxide ion conductivity over a wide
      range of oxygen partial pressure. The crystal structure of La(2)GeO(5) was
      estimated to be monoclinic with P2(1)/c space group. Conductivity increased with
      increasing the amount of La deficiency and the maximum value was attained at x =
      0.39 in La(2 - x)GeO(5 - delta). The oxide ion transport number in La(2)GeO(5)
      based oxide was estimated to be unity by the electromotive force measurement in
      H(2)-O(2) and N(2)-O(2) gas concentration cells. At a temperature higher than
      1000 K, the oxide ion conductivity of La(1.61)GeO(5 - delta) was almost the same
      as that of La(0.9)Sr(0.1)Ga(0.8)Mg(0.2)O(3 - delta) or Ce(0.85)Gd(0.15)O(2 -
      delta), which are well-known fast oxide ion conductors. On the other hand, a
      change in the activation energy for oxide ion conductivity was observed at 973 K,
      and at intermediate temperature, the oxide ion conductivity of La(1.61)GeO(5 -
      delta) became much smaller than that of these well-known fast oxide ion
      conductors. The change in the activation energy of the oxide ion conductivity
      seems to be caused by a change in the local oxygen vacancy structure. However,
      doping a small amount of Sr for La in La(2)GeO(5) was effective to stabilize the
      high-temperature crystal structure to low temperature. Consequently, doping a
      small amount of Sr increases the oxide ion conductivity of La(2)GeO(5)-based
      oxide at low temperature.

PMID- 11456506
TI  - Catalysis of the methanolysis of activated amides by divalent and trivalent metal
      ions. The effect of Zn(2+), Co(2+), and La(3+) on the methanolysis of
      acetylimidazole and its (NH(3))(5)Co(III) complex.
AB  - The metal ions Zn(2+), Co(2+), and La(3+) strongly catalyze the methanolysis of
      the activated amides acetylimidazole (1) and its ligand-exchange-inert Co(III)
      complex, (NH(3))(5)Co(III)-AcIm (2). Studies of the kinetics of methanolysis are
      performed with pH measurement and control, and the metal ions are soluble in the
      medium throughout the pH regions where ionization of the M(x+)(CH(3)OH)(y)
      occurs. Zn(2+) and Co(2+) act as Lewis acids toward 1, catalyzing attack of
      external methoxide on a 1:M(2+) complex at values only 100-fold lower than the
      diffusion limit, the k(OR) values being 5.6 x 10(7) M(-1) s(-1) and 2.5 x 10(7)
      M(-1) s(-1), while that for CH(3)O(-) attack on 2 is 4.69 x 10(7) M(-1) s(-1).
      Since neither Zn(2+) nor Co(2+) promotes the methanolysis of 2, these metals
      appear to be acting through transient binding to the distal N of 1, which
      activates the C=O of the complex to external CH(3)O(-) attack. La(3+) catalyzes
      the methanolysis of both 1 and 2, which occurs by a mechanism that is
      fundamentally different from that exhibited by Zn(2+) and Co(2+) in that the
      active species appears to be a bis-methoxy-bridged dimer (La(3+))(2)(CH(3)O(
      ))(2)(CH(3)OH)(x)() that interacts directly with the C=O unit of the substrate.

PMID- 11456507
TI  - An ionic liquid form of DNA: redox-active molten salts of nucleic acids.
AB  - Ionic liquids are described that contain duplex DNA as the anion and polyether
      decorated transition metal complexes based on M(MePEG-bpy)(3)(2+) as the cation
      (M = Fe, Co; MePEG-bpy = 4,4'-(CH(3)(OCH(2)CH(2))(7)OCO)(2)-2,2'-bipyridine).
      When the undiluted liquid DNA-or molten salt-is interrogated electrochemically by
      a microelectrode, the molten salts exhibit cyclic voltammograms due to the
      physical diffusion (D(PHYS)) of the polyether-transition metal complex. When M =
      Co(II), the cyclic voltammogram of the melt shows an oxidative wave due to the
      Co(III/II) couple at E(1/2) = 0.40 V (versus Ag/AgCl) and a D(PHYS) of 6 x 10(
      12) cm(2)/s, which is significantly lower than that for Co(MePEG
      bpy)(3)(ClO(4))(2) (D(PHYS) = 2.6 x 10(-10) cm(2)/s) due to greater viscosity
      provoked by the DNA polymer. When a 1:1 mixture is made of the Co(MePEG
      bpy)(3).DNA and Fe(MePEG-bpy)(3)(ClO(4))(2) melts, two redox waves are observed.
      The first is due to the Co(III/II) couple, and the second is a catalytic wave due
      to oxidation of guanine in DNA by electrogenerated Fe(III) in the undiluted melt.
      Independent experiments show that the Fe(III) form of the complex selectively
      oxidizes guanine in duplex DNA. These DNA molten salts constitute a new class of
      materials whose properties can be controlled by nucleic acid sequence and that
      can be interrogated in undiluted form on microelectrode arrays.

PMID- 11456508
TI  - Synthesis, structures, and reactivity of weakly coordinating anions with
      delocalized borate structure: the assessment of anion effects in metallocene
      polymerization catalysts.
AB  - The formation of adducts of tris(pentafluorophenyl)borane with strongly
      coordinating anions such as CN(-) and [M(CN)(4)](2)(-) (M = Ni, Pd) is a
      synthetically facile route to the bulky, very weakly coordinating anions
      [CN[B(C(6)F(5))(3)](2)](-) and [M[CNB(C(6)F(5))(3)](4)](2-) which are isolated as
      stable NHMe(2)Ph(+) and CPh(3)(+) salts. The crystal structures of
      [CPh(3)][CN[B(C(6)F(5))(3)](2)] (1), [CPh(3)][ClB(C(6)F(5))(3)] (2),
      [NHMe(2)Ph](2)[Ni[CNB(C(6)F(5))(3)](4)].2Me(2)CO (4b.2Me(2)CO),
      [CPh(3)](2)[Ni[CNB(C(6)F(5))(3)](4)].2CH(2)Cl(2) (4c.2CH(2)Cl(2)), and
      [CPh(3)](2)[Pd[CNB(C(6)F(5))(3)](4)].2CH(2)Cl(2) (5c.2CH(2)Cl(2)) are reported.
      The CN stretching frequencies in 4 and 5 are shifted by approximately 110 cm(-1)
      to higher wavenumbers compared to the parent tetracyano complexes in aqueous
      solution, although the M-C and C-N distances show no significant change on
      B(C(6)F(5))(3) coordination. Zirconocene dimethyl complexes L(2)ZrMe(2) [L(2) =
      Cp(2), SBI = rac-Me(2)Si(Ind)(2)] react with 1, 4c or 5c in benzene solution at
      20 degrees C to give the salts of binuclear methyl-bridged cations,
      [(L(2)ZrMe)(2)(mu-Me)][CN[B(C(6)F(5))(3)](2)] and [(L(2)ZrMe)(2)(mu
      Me)](2)[M[CNB(C(6)F(5))(3)](4)]. The reactivity of these species in solution was
      studied in comparison with the known [[(SBI)ZrMe](2)(mu-Me)][B(C(6)F(5))(4)].
      While the latter reacts with excess [CPh(3)][B(C(6)F(5))(4)] in benzene to give
      the mononuclear ion pair [(SBI)ZrMe(+).B(C(6)F(5))(4)(-)] in a pseudo-first-order
      reaction, k = 3 x 10(-4) s(-1), [(L(2)ZrMe)(2)(mu-Me)][CN[B(C(6)F(5))(3)](2)]
      reacts to give a mixture of L(2)ZrMe(mu-Me)B(C(6)F(5))(3) and L(2)ZrMe(mu
      NC)B(C(6)F(5))(3). Recrystallization of [Cp' '(2)Zr(mu
      Me)(2)AlMe(2)][CN[B(C(6)F(5))(3)](2)] affords Cp' '(2)ZrMe(mu-NC)B(C(6)F(5))(3)
      6, the X-ray structure of which is reported. The stability of [(L(2)ZrMe)(2)(mu
      Me)](+)X(-) decreases in the order X = [B(C(6)F(5))(4)] >
      [M[CNB(C(6)F(5))(3)](4)] > [CN[B(C(6)F(5))(3)](2)] and increases strongly with
      the steric bulk of L(2) = Cp(2) << SBI. Activation of (SBI)ZrMe(2) by 1 in the
      presence of AlBu(i)(3) gives extremely active ethene polymerization catalysts.
      Polymerization studies at 1-7 bar monomer pressure suggest that these, and by
      implication most other highly active ethene polymerization catalysts, are
      strongly mass-transport limited. By contrast, monitoring propene polymerization
      activities with the systems (SBI)ZrMe(2)/1/AlBu(i)(3) and CGCTiMe(2)/1/AlBu(i)(3)
      at 20 degrees C as a function of catalyst concentration demonstrates that in
      these cases mass-transport limitation is absent up to [metal] approximately 2 x
      10(-5) mol L(-1). Propene polymerization activities decrease in the order
      [CN[B(C(6)F(5))(3)](2)](-) > [B(C(6)F(5))(4)](-) > [M[CNB(C(6)F(5))(3)](4)](2-)
      >> [MeB(C(6)F(5))(3)](-), with differences in activation barriers relative to
      [CN[B(C(6)F(5))(3)](2)](-) of DeltaDeltaG = 1.1 (B(C(6)F(5))(4)(-)), 4.1
      (Ni[CNB(C(6)F(5))(3)](4)(2-)) and 10.7-12.8 kJ mol(-)(1) (MeB(C(6)F(5))(3)(-)).
      The data suggest that even in the case of very bulky anions with delocalized
      negative charge the displacement of the anion by the monomer must be involved in
      the rate-limiting step.

PMID- 11456509
TI  - Spectroscopy and reactivity of Kekule hydrocarbons with very small singlet
      triplet gaps.
AB  - Two Kekule hydrocarbons, 2,2-dimethyl-2H-benzo[cd]fluoranthene (1) and its
      benzannellated analogue 2,2-dimethyl-2H-dibenzo[cd,k]fluoranthene (2), were
      generated photochemically from two different photoprecursors each and
      investigated spectroscopically in cryogenic matrices by UV-vis, fluorescence, and
      EPR and in solution using ns flash photolysis and chemical trapping experiments.
      Hydrocarbon 1 is a ground-state singlet species, whereas compound 2 has a triplet
      ground state, the first such neutral Kekule hydrocarbon. This difference, which
      is supported by density functional calculations, has profound influence on the
      spectroscopy and reactivity of the two compounds. Using the results of the
      spectroscopic measurements, trapping experiments, and density functional
      calculations, the singlet-triplet gap for 1 is estimated to be 2.3-2.8 kcal mol(
      1), with the singlet the ground state, and 0.8-1.3 kcal mol(-1) for 2, in favor
      of the triplet.

PMID- 11456510
TI  - Hydrazino peptides as foldamers: an extension of the beta-peptide concept.
AB  - Replacing the C(beta) atoms in the beta-amino acid constituents of beta-peptides
      by nitrogen atoms leads to hydrazino peptides. A systematic conformation analysis
      of blocked hydrazino peptide oligomers of the general type I at the HF/6-31G,
      MP2/6-31G, and DFT/B3LYP/6-31G levels of ab initio MO theory and on the basis of
      molecular mechanics reveals a wide variety of secondary structures, as for
      instance various helices and sheet- and turnlike conformers. Some of them are
      closely related to secondary structure types found in beta-peptides; others
      represent novel types. Thus, a very stable, novel helix with 14-membered hydrogen
      bonded pseudocycles, which occupies a conformation space different from that of
      helices with 14-membered rings found among the most stable conformers in beta
      peptides, is indicated. The most important secondary structure elements are
      characterized by interactions between peptidic NH and CO groups. The additional
      hydrazino N(alpha)H group takes part in special structuring effects but is of
      lesser importance for secondary structure formation. The influence of
      environmental effects on the existence and stability of the various structure
      types is discussed. Due to the wide variety of structural possibilities,
      hydrazino peptides might be a useful tool for peptide and protein design.

PMID- 11456511
TI  - Reversible Diels-Alder addition to fullerenes: a study of equilibria using (3)He
      NMR spectroscopy.
AB  - 3He NMR spectroscopy has been used to study the equilibria of Diels-Alder
      additions of 9,10-dimethyl anthracene (DMA) to (3)He@C(60) and (3)He@C(70).
      Spectra of a series of equilibrium mixtures showed peaks for the isomeric
      adducts. One monoadduct, six bis-adducts, eleven tris-adducts, and ten tetrakis
      adducts of DMA to C(60) were seen. One monoadduct and three bis-adducts of C(70)
      were detected. Equilibrium constants were found for these reactions and values
      for DeltaG, DeltaH, and DeltaS were obtained.

PMID- 11456512
TI  - Charge hopping in DNA.
AB  - The efficiency of charge migration through stacked Watson-Crick base pairs is
      analyzed for coherent hole motion interrupted by localization on guanine (G)
      bases. Our analysis rests on recent experiments, which demonstrate the
      competition of hole hopping transitions between nearest neighbor G bases and a
      chemical reaction of the cation G(+) with water. In addition, it has been assumed
      that the presence of units with several adjacent stacked G bases on the same
      strand leads to the additional vibronic relaxation process (G(+)G...G) -->
      (GG...G)(+). The latter may also compete with the hole transfer from (G(+)G...G)
      to a single G site, depending on the relative positions of energy levels for G(+)
      and (G(+)G...G). A hopping model is proposed to take the competition of these
      three rate steps into account. It is shown that the model includes two important
      limits. One corresponds to the situation where the charge relaxation inside a
      multiple guanine unit is faster than hopping. In this case hopping is terminated
      by several adjacent G bases located on the same strand, as has been observed for
      the GGG triple. In the opposite, slow relaxation limit the GG...G unit allows a
      hole to migrate further in accord with experiments on strand cleavage exploiting
      GG pairs. We demonstrate that for base pair sequences with only the GGG triple,
      the fast relaxation limit of our model yields practically the same sequence- and
      distance dependencies as measurements, without invoking adjustable parameters.
      For sequences with a certain number of repeating adenine:thymine pairs between
      neighboring G bases, our analysis predicts that the hole transfer efficiency
      varies in inverse proportion to the sequence length for short sequences, with
      change to slow exponential decay for longer sequences. Calculations performed
      within the slow relaxation limit enable us to specify parameters that provide a
      reasonable fit of our numerical results to the hole migration efficiency deduced
      from experiments with sequences containing GG pairs. The relation of the results
      obtained to other theoretical and experimental studies of charge transfer in DNA
      is discussed. We propose experiments to gain a deeper insight into complicated
      kinetics of charge-transfer hopping in DNA.

PMID- 11456513
TI  - Hydrogen-bonding interactions in the active sites of cytochrome P450cam and its
      site-directed mutants.
AB  - Resonance Raman spectroscopy is applied to the cyanide adducts of cytochrome
      P450cam and its T252A and D251N site-directed mutants, both in their substrate
      free and camphor-bound forms, to probe active-site heme structure and, in
      particular, interactions of the FeCN fragment with potential active-site H-bond
      donors. In contrast to the ferrous CO and ferric NO adducts, which form only
      essentially linear (slightly distorted) FeXY fragments, the spectra of the ferric
      CN(-) adducts provide clear evidence the for the existence of an additional,
      rather highly bent, conformer; that is, the cyanide complexes form both linear
      and bent conformers in both the substrate-free and substrate-bound forms.
      Formation of this bent conformer is most reasonably attributed to the presence of
      off-axis H-bond donors, which induce distortion on the FeCN fragment but not the
      FeCO and FeNO fragments, which are poorer H-bond acceptors. For all three
      proteins, the substrate-free form exhibits a complex spectral pattern which
      arises because one of the modes associated with the FeCN fragment is coupled with
      two heme macrocycle deformation modes. Significantly, no evidence for such
      coupling is observed in the spectra of the camphor-bound forms. While various
      unknown factors may possibly give rise to selective activation of such coupling
      in the substrate-free derivative, given the known facts about the active-site
      architecture of this enzyme, a plausible explanation is that the bent conformer
      is oriented toward the water-filled substrate-binding site in the substrate-free
      form, but oppositely, toward the proposed proton delivery shuttle, in the
      substrate-bound form. Sensitivity of the FeCN modes to H(2)O/D(2)O exchange in
      the two camphor-bound mutants, which is apparently absent for the camphor-bound
      native protein, is most reasonably attributed to the known presence of extra
      water in the active sites of these mutants.

PMID- 11456514
TI  - High-pressure NMR study of cis-1,n-disubstituted[n]paracyclophanes. Effect of
      increased pressure on the hindered internal rotation.
AB  - The effect of hydrostatic pressure on the rate of internal rotation of title
      compounds has been examined by the DNMR method. Quartz pressure-resisting NMR
      cells were used to realize the high-pressure experiments up to 390 (line shape
      measurements) and 450 MPa (chemical shift measurements). Application of
      hydrostatic pressure was found to accelerate the rotation of the benzene ring,
      while pressure-induced low-frequency chemical shifts of bridge methylene protons
      indicated that there is a considerable shrinkage of the methylene bridge
      structure upon pressurization.

PMID- 11456515
TI  - Mechanistic studies on the reversible binding of nitric oxide to metmyoglobin.
AB  - The ferriheme protein metmyoglobin (metMb) in buffer solution at physiological pH
      7.4 reversibly binds the biomessenger molecule nitric oxide to yield the nitrosyl
      adduct (metMb(NO)). The kinetics of the association and dissociation processes
      were investigated by both laser flash photolysis and stopped-flow kinetics
      techniques at ambient and high pressure, in three laboratories using several
      different sources of metMb. The activation parameters DeltaH, DeltaS, and DeltaV
      were calculated from the kinetic effects of varying temperature and hydrostatic
      pressure. For the "on" reaction of metMb plus NO, reasonable agreement was found
      between the various techniques with DeltaH(on), DeltaS(on), and DeltaV(on)
      determined to have the respective values approximately 65 kJ mol(-1),
      approximately 60 J mol(-1) K(-1), and approximately 20 cm(3) mol(-1). The large
      and positive DeltaS and DeltaV values are consistent with the operation of a
      limiting dissociative ligand substitution mechanism whereby dissociation of the
      H(2)O occupying the sixth distal coordination site of metMb must precede
      formation of the Fe-NO bond. While the activation enthalpies of the "off"
      reaction displayed reasonable agreement between the various techniques (ranging
      from 68 to 83 kJ mol(-1)), poorer agreement was found for the DeltaS(off) values.
      For this reason, the kinetics for the "off" reaction were determined more
      directly via NO trapping experiments, which gave the respective activation
      parameters DeltaH(off) = 76 kJ mol(-1), DeltaS(off) = approximately 41 J mol(-1)
      K(-1), and DeltaV(off) = 20 cm(3) mol(-1)), again consistent with a limiting
      dissociative mechanism. These results are discussed in reference to other
      investigations of the reactions of NO with both model systems and
      metalloproteins.

PMID- 11456516
TI  - pi-topology and spin alignment utilizing the excited molecular field: observation
      of the excited high-spin quartet (S = 3/2) and quintet (S = 2) states on purely
      organic pi-conjugated spin systems.
AB  - As a model system for the photoinduced/photoswitched spin alignment in a purely
      organic pi-conjugated spin system, 9-[4-(4,4,5,5-tetramethyl-1-yloxyimidazolin-2
      yl)phenyl]anthracene (1a), 9-[3-(4,4,5,5-tetramethyl-1-yloxyimidazolin-2
      yl)phenyl]anthracene (1b), 9,10-bis[4-(4,4,5,5-tetramethyl-1-yloxyimidazolin-2
      yl)phenyl]anthracene (2a), and 9,10-bis[3-(4,4,5,5-tetramethyl-1-yloxyimidazolin
      2-yl)phenyl]anthracene (2b) were designed and synthesized. In these spin systems,
      9-phenylanthracene and 9,10-diphenylanthracene were chosen as photo spin couplers
      and iminonitroxide was chosen as a dangling stable radical. Time-resolved
      electron spin resonance (TRESR) spectra of the first excited states with resolved
      fine-structure splittings were observed for 1a and 2a in an EPA or a 2-MTHF rigid
      glass matrix. Using the spectral simulation based on the eigenfield method, the
      observed TRESR spectra for 1a and 2a were unambiguously assigned as an excited
      quartet (S = 3/2) spin state (Q) and an excited quintet (S = 2) spin state (Qu),
      respectively. The g value and fine-structure splitting for the quartet state of
      1a were determined to be g(Q) = 2.0043, D(Q) = 0.0235 cm(-1), and E(Q) = 0.0 cm(
      1). The relative populations (polarization) of each M(S)() sublevel in Q were
      determined to be P(+1/2') = P(-1/2') = 0.5 and P(+3/2') = P(-3/2') = 0.0 with an
      increasing order of energy in zero magnetic field. The spin Hamiltonian
      parameters for Qu are g = 2.0043, D = 0.0130 cm(-1), and E = 0.0 cm(-1), and the
      relative populations in Qu were determined to be P(0') = 0.30, P(-1') = P(+1') =
      0.35 and P(-2') = P(+2') = 0.0. These are the first observations of a
      photoexcited quartet and a quintet high-spin state in pi-conjugated triplet
      radical pair systems. In contrast high-spin excited states were not observed for
      1b and 2b, the pi-topological isomers of 1a and 2a, showing the role of pi
      topology in the spin alignment of the excited states. Since a weak
      antiferromagnetic exchange interaction was observed in the ground state of 2a,
      the clear detection of the excited quintet high-spin state shows that the
      effective exchange coupling between the two dangling radicals through the
      diphenylanthracene spin coupler has been changed from antiferromagnetic to
      ferromagnetic upon photoexcitation. Thus, a photoinduced spin alignment utilizing
      the excited triplet molecular field was realized for the first time in the purely
      organic pi-conjugated spin system. Furthermore, the mechanism for the generation
      of dynamic electron spin polarization was investigated for the observed quartet
      and quintet states, and a plausible mechanism of the enhanced selective
      intersystem crossing was proposed. Ab initio molecular orbital calculations based
      on density functional theory were carried out to determine the electronic
      structures of the excited high-spin states and to understand the mechanism of the
      spin alignment utilizing the excited molecular field. The role of the spin
      delocalization and the spin polarization mechanisms were revealed on the
      photoexcited state.

PMID- 11456517
TI  - A novel antiferromagnetic organic superconductor kappa-(BETS)(2)FeBr(4) [where
      BETS = bis(ethylenedithio)tetraselenafulvalene].
AB  - The electrical and magnetic properties of kappa-(BETS)(2)FeBr(4) salt [where BETS
      = bis(ethylenedithio)tetraselenafulvalene] showed that this system is the first
      antiferromagnetic organic metal at ambient pressure (T(N) = 2.5 K). The
      characteristic field dependence of the magnetization at 2.0 K indicates a clear
      metamagnetic behavior. The small resistivity drop observed at T(N) clearly shows
      the existence of the interaction between pi metal electrons and localized
      magnetic moments of Fe(3+) ions. In addition, this system underwent a
      superconducting transition at 1.1 K. That is, kappa-(BETS)(2)FeBr(4) is the first
      antiferromagnetic organic metal exhibiting a superconducting transition below
      Neel temperature. The magnetic field dependence of the superconducting critical
      temperature indicated that the superconductivity in this system is strongly
      anisotropic also in the conduction plane because of the existence of the
      metamagnetically induced internal field based on the antiferromagnetic ordering
      of the Fe(3+) 3d spins in contrast to the cases of the other conventional organic
      superconductors. Furthermore, the specific heat measurement exhibited a lambda
      type large peak of zero-field specific heat corresponding to the three
      dimensional antiferromagnetic ordering of high-spin Fe(3+) ions. The lack of
      distinct anomaly in the C(p) vs T curve at T(c) suggests the coexistence of the
      superconductivity and the antiferromagnetic order below T(c).

PMID- 11456518
TI  - Complex-induced proximity effects: the effect of varying directing-group
      orientation on carbamate-directed lithiation reactions.
AB  - A series of selected bicyclic carbamates in which the range of accessible angles
      and distances between the carbonyl group and the proton removed in an alpha
      lithiation reaction are structurally defined have been investigated.
      Oxazolidinones 7-10 undergo stereoselective lithiation-substitution reactions to
      provide cis-18-27 and cis-31-35 as the major diastereomers. Two series of
      competition experiments show that the conformationally restricted carbamates 7,
      10, 11, and 15 undergo lithiation via complexes more efficiently than Boc amines
      4-6. These results along with semiempirical calculations suggest that a small
      dihedral angle and a calculated distance of 2.78 A between the carbamate carbonyl
      oxygen and the proton to be removed are favorable for a carbamate-directed
      lithiation. A series of tin-lithium exchange experiments on cis- and trans-18 and
      (S)-39 indicate that the configurational stability of a carbamate-stabilized
      organolithium species may be enhanced by restrictive geometry.

PMID- 11456519
TI  - A crossed molecular beam study of the O(1D) + C(3)H(8) reaction: multiple
      reaction pathways.
AB  - The O((1)D) + C(3)H(8) reaction has been reinvestigated using the universal
      crossed molecular beam method. Three reaction channels, CH(3) + C(2)H(4)OH,
      C(2)H(5) + CH(2)OH, and OH + C(3)H(7), have been observed. All three channels are
      significant in the title reaction with the C(2)H(5) formation process to be the
      most important, while the CH(3) formation and the OH formation channels are about
      equal. Product kinetic energy distributions and angular distributions have been
      determined for the three reaction channels observed. The oxygen-containing
      radicals in the CH(3) and C(2)H(5) formation pathways show forward-backward
      symmetric angular distribution relative to the O atom beam, while the OH product
      shows a clearly forward angular distribution. These results indicate that the OH
      formation channel seems to exhibit different dynamics from the CH(3) and C(2)H(5)
      channels.

PMID- 11456520
TI  - Organometallic cobalt(II) and nickel(II) complexes supported by thioether
      ligation: unexpected nickel alkylation by the borato ligand phenyltris((tert
      butylthio)methyl)borate.

PMID- 11456521
TI  - Novel cylindrical, conical, and macrocyclic peptides from the
      cyclooligomerization of functionalized thiazole amino acids.

PMID- 11456522
TI  - Photoactive three-dimensional monolayers: porphyrin-alkanethiolate-stabilized
      gold clusters.

PMID- 11456523
TI  - Ru-catalyzed oxidative coupling of arenes with olefins using O(2).

PMID- 11456524
TI  - Rapid and controlled polymerization of lactide by structurally characterized
      ferric alkoxides.

PMID- 11456525
TI  - Formal total synthesis of mycoticin A.

PMID- 11456526
TI  - A parallel beta-sheet model system that folds in water.

PMID- 11456527
TI  - The stereospecificity of secondary alcohol dehydrogenase from Thermoanaerobacter
      ethanolicus is partially determined by active site water.

PMID- 11456528
TI  - Dimers of diaminosilylenes: doubly bonded or bridged? The dimers of (i
      Pr(2)N)(2)Si:.

PMID- 11456529
TI  - Enzymatic N-dealkylation of an N-cyclopropylamine: an unusual fate for the
      cyclopropyl group.

PMID- 11456530
TI  - The total synthesis of (+/-)-rishirilide B.

PMID- 11456531
TI  - Planar-chiral pyridine N-oxides, a new family of asymmetric catalysts: exploiting
      an eta(5)-C(5)Ar(5) ligand to achieve high enantioselectivity.

PMID- 11456532
TI  - Palladium-catalyzed formation of aceanthrylenes: a simple method for peri
      cyclopentenelation of aromatic compounds.

PMID- 11456533
TI  - Construction of glyco-clusters by self-organization of site-specifically
      glycosylated oligonucleotides and their cooperative amplification of lectin
      recognition.

PMID- 11456534
TI  - Coupling of substrate recognition and catalysis by a human base-excision DNA
      repair protein.

PMID- 11456535
TI  - Reaction microarrays: a method for rapidly determining the enantiomeric excess of
      thousands of samples.

PMID- 11456540
TI  - Aromatic ring-flipping in supercooled water: implications for NMR-based
      structural biology of proteins.
AB  - We have characterized, for the first time, motional modes of a protein dissolved
      in supercooled water: the flipping kinetics of phenylalanyl and tyrosinyl rings
      of the 6 kDa protein BPTI have been investigated by NMR at temperatures between 
      3 and -16.5 degrees C. At T = -15 degrees C, the ring-flipping rate constants of
      Tyr 23, Tyr 35, and Phe 45 are smaller than 2 s(-1), i.e., flip-broadening of
      aromatic NMR lines is reduced beyond detection and averaging of NOEs through ring
      flipping is abolished. This allows neat detection of distinct NOE sets for the
      individual aromatic (1)H spins. In contrast, the rings of Phe 4, Tyr 10, Tyr 21,
      Phe 22, and Phe 33 are flipping rapidly on the chemical shift time scale with
      rate constants being in the range from approximately 10(2) to 10(5) s(-1) even at
      T = -15 degrees C. Line width measurements in 2D [(1)H,(1)H]-NOESY showed that
      flipping of the Phe 4 and Phe 33 rings is, however, slowed to an extent that the
      onset of associated line broadening in the fast exchange limit is registered. The
      reduced ring-flipping rate constant of Phe 45 in supercooled water allowed very
      precise determination of Eyring activation enthalpy and entropy from cross
      relaxation suppressed 2D [(1)H,(1)H]-exchange spectroscopy. This yielded DeltaH =
      14 +/- 0.5 kcal.mol(-1) and DeltaS = -4 +/- 1 cal.mol(-1).K(-1), i.e., values
      close to those previously derived by Wagner and Wuthrich for the temperature
      range from 4 to 72 degrees C (DeltaH = 16 +/- 1 kcal.mol(-1) and DeltaS = 6 +/- 2
      cal.mol(-1).K(-1)). The preservation of the so far uniquely low value for DeltaS
      indicates that the distribution of internal motional modes associated with the
      ring flip of Phe 45 is hardly affected by lowering T well below 0 degrees C.
      Hence, if a globular protein does not cold denature, aromatic flipping rates, and
      thus likely also the rates of other conformational and/or chemical exchange
      processes occurring in supercooled water, can be expected to be well estimated
      from activation parameters obtained at ambient T. This is of keen interest to
      predict the impact of supercooling for future studies of biological
      macromolecules, and shows that our approach enables one to conduct NMR-based
      structural biology at below 0 degrees C in an unperturbed aqueous environment. A
      search of the BioMagResBank indicated that the overwhelming majority of the Phe
      and Tyr rings (>95%) are flipping rapidly on the chemical shift time scale at
      ambient T, while our data for BPTI and activation parameters available for ring
      flipping in Iso-2-cytochrome c reveal that in these smaller proteins a total of
      six out of seventeen rings ( approximately 35%) are "frozen in" at T = -15
      degrees C. This suggests that a large fraction of Tyr and Phe rings in globular
      proteins that are flipping rapidly on the chemical shift time scale at ambient T
      can be effectively slowed in supercooled water. The present investigation
      demonstrates that supercooling of protein solutions appears to be an effective
      means to (i) harvest potential benefits of stalled ring-flipping for refining NMR
      solution structures, (ii) recruit additional aromatic rings for investigating
      protein dynamics, and (iii) use multiple slowly flipping rings to probe cold
      denaturation. The implications for NMR-based structural biology in supercooled
      water are addressed.

PMID- 11456541
TI  - A synthetic library of cell-permeable molecules.
AB  - Small molecules that induce or stabilize the association of macromolecules have
      proven to be useful effectors of a wide variety of biological processes. To date,
      all examples of such chemical inducers of dimerization have involved known
      ligands to well-characterized proteins. The generality of this approach could be
      broadened by enabling the discovery of heterodimerizers that target known
      macromolecules having no established ligand, or heterodimerizers that produce a
      novel biologic response in screens having no predetermined macromolecular target.
      Toward this end, we report the construction of a diversified library of synthetic
      heterodimerizers consisting of an invariant ligand that targets the FK506-binding
      protein (AP1867) attached to 320 substituted tetrahydrooxazepines (THOXs). The
      THOX components were generated by a combination of liquid- and solid-phase
      procedures employing sequential Mitsonobu displacements to join two structurally
      diversified olefin-containing monomers, followed by ruthenium-mediated olefin
      metathesis to effect closure of the seven-membered ring. The 320 resin-bound THOX
      ligands were coupled in parallel to AP1867, and the products were released from
      the resin to yield candidate heterodimerizers in sufficient yield and purity to
      be used directly in biologic testing. A representative panel of 25 candidate
      heterodimerizers were tested for their ability to pass through the membrane of
      human fibrosarcoma cells, and all were found to possess activity in this tissue
      culture system. These studies pave the way for further studies aimed at using
      small-molecule inducers of heterodimerization to effect novel biological
      responses in intact cells.

PMID- 11456543
TI  - Rapid colorimetric detection of antibody-epitope recognition at a biomimetic
      membrane interface.
AB  - Biomolecular recognition of antigens and epitopes by antibodies is a fundamental
      event in the initiation of immune response and plays a central role in a variety
      of biochemical processes. Peptide binding requires, in many cases, presentation
      of the peptides at interfaces, such as protein surfaces, cellular membranes, and
      synthetic polymer surfaces. We describe a novel molecular system in which
      interactions between antibodies and peptide epitopes displayed at a biomimetic
      membrane interface can be detected through induction of visible, rapid color
      transitions. The colorimetric assembly consists of a phospholipid/polydiacetylene
      matrix anchoring a hydrophobic peptide displaying the epitope at its N-terminus.
      The colorimetric transitions observed in the assembly, corresponding to
      perturbation of the polydiacetylene framework, are induced only upon recognition
      of the displayed epitope by its specific antibody present in the aqueous
      solution. Significantly, the color changes occur after a single mixing step,
      without further chemical reactions or enzymatic processing. The new molecular
      system could be utilized for studying antigen-antibody interactions and peptide
      protein recognition, epitope mapping, and rapid screening of biological and
      chemical libraries.

PMID- 11456544
TI  - Characterization of the O(2)-evolving reaction catalyzed by
      [(terpy)(H2O)Mn(III)(O)2Mn(IV)(OH2)(terpy)](NO3)3 (terpy = 2,2':6,2"
      terpyridine).
AB  - The complex [(terpy)(H(2)O)Mn(III)(O)(2)Mn(IV)(OH(2))(terpy)](NO(3))(3) (terpy =
      2,2':6,2' '-terpyridine) (1)catalyzes O(2) evolution from either KHSO(5)
      (potassium oxone) or NaOCl. The reactions follow Michaelis-Menten kinetics where
      V(max) = 2420 +/- 490 mol O(2) (mol 1)(-1) hr(-1) and K(M) = 53 +/- 5 mM for
      oxone ([1] = 7.5 microM), and V(max) = 6.5 +/- 0.3 mol O(2) (mol 1)(-1) hr(-1)
      and K(M) = 39 +/- 4 mM for hypochlorite ([1] = 70 microM), with first-order
      kinetics observed in 1 for both oxidants. A mechanism is proposed having a
      preequilibrium between 1 and HSO(5-) or OCl(-), supported by the isolation and
      structural characterization of [(terpy)(SO(4))Mn(IV)(O)(2)Mn(IV)(O(4)S)(terpy)]
      (2). Isotope-labeling studies using H(2)(18)O and KHS(16)O(5) show that O(2)
      evolution proceeds via an intermediate that can exchange with water, where Raman
      spectroscopy has been used to confirm that the active oxygen of HSO(5-) is
      nonexchanging (t(1/2) >> 1 h). The amount of label incorporated into O(2) is
      dependent on the relative concentrations of oxone and 1.
      (32)O(2):(34)O(2):(36)O(2) is 91.9 +/- 0.3:7.6 +/- 0.3:0.51 +/- 0.48, when [HSO(5
      )] = 50 mM (0.5 mM 1), and 49 +/- 21:39 +/- 15:12 +/- 6 when [HSO(5-)] = 15 mM
      (0.75 mM 1). The rate-limiting step of O(2) evolution is proposed to be formation
      of a formally Mn(V)=O moiety which could then competitively react with either
      oxone or water/hydroxide to produce O(2). These results show that 1 serves as a
      functional model for photosynthetic water oxidation.

PMID- 11456545
TI  - Hydration of the calcium ion. An EXAFS, large-angle x-ray scattering, and
      molecular dynamics simulation study.
AB  - The structure of the hydrated calcium(II) ion in aqueous solution has been
      studied by means of extended X-ray absorption fine structure spectroscopy
      (EXAFS), large-angle X-ray scattering (LAXS), and molecular dynamics (MD)
      methods. The EXAFS data displayed a broad and asymmetric distribution of the Ca-O
      bond distances with the centroid at 2.46(2) A. LAXS studies on four aqueous
      calcium halide solutions (1.5-2 mol dm(-)(3)) gave a mean Ca-O bond distance of
      2.46(1) A. This is consistent with a hydration number of 8 determined from
      correlations between mean distances and coordination numbers from crystal
      structures. The LAXS studies showed a second coordination sphere with a mean
      Ca.O(II) distance of 4.58(5) A, and for the hydrated halide ions the distances
      Cl.O 3.25(1) A, Br.O 3.36(1) A, and I.O 3.61(1) A were obtained. Molecular
      dynamics simulations of CaCl(2)(aq) were performed using three different Ca(2+)
      OH(2) pair potentials. The potential from the GROMOS program gave results in
      agreement with experiments, i.e., a coordination number of 8 and an average Ca-O
      distance of 2.46 A, and was used for further comparisons. Theoretical EXAFS
      oscillations were computed for individual MD snapshots and showed very large
      variations, though the simulated average spectrum from 2000 snapshots gave
      satisfactory agreement with the experimental EXAFS spectra. The effect of thermal
      motions of the coordinated atoms is inherent in the MD simulation method. Thermal
      disorder parameters evaluated from simulated spatial atom distribution functions
      of the oxygen atoms coordinated to the calcium ion were in close agreement with
      those from the current LAXS and EXAFS analyses. The combined results are
      consistent with a root-mean-square displacement from the mean Ca-O distance of
      0.09(2) A in aqueous solution at 300 K.

PMID- 11456546
TI  - S K-edge X-ray absorption studies of tetranuclear iron-sulfur clusters: mu
      sulfide bonding and its contribution to electron delocalization.
AB  - X-ray absorption spectroscopy (XAS) at the sulfur ( approximately 2470 eV) and
      chlorine ( approximately 2822 eV) K-edges has been applied to a series of 4Fe-4S
      model complexes. These are compared to 2Fe-2S model complexes to obtain insight
      into the localized ground state in the mixed-valence dimer versus the delocalized
      ground state in the mixed-valence tetramer. The preedges of hypothetical
      delocalized mixed-valence dimers [Fe(2)S(2)](+) are estimated using trends from
      experimental data and density functional calculations, for comparison to the
      delocalized mixed-valence tetramer [Fe(4)S(4)](2+). The differences between these
      two mixed-valence sites are due to the change of the sulfide-bridging mode from
      micro(2) to micro(3). The terminal chloride and thiolate ligands are used as
      spectator ligands for the electron density of the iron center. From the intensity
      of the preedge, the covalency of the terminal ligands is found to increase in the
      tetramer as compared to the dimer. This is associated with a higher effective
      nuclear charge on the iron in the tetramer (derived from the energies of the
      preedge). The micro(3)-bridging sulfide in the tetramer has a reduced covalency
      per bond (39%) as compared to the micro(2)-bridging sulfide in the dimer (51%). A
      simple perturbation model is used to derive a quadratic dependence of the
      superexchange coupling constant J on the covalency of the metal ions with the
      bridging ligands. This relationship is used to estimate the superexchange
      contribution in the tetramer (J = -156 cm(-)(1)) as compared to the mixed-valence
      dimer (J = -360 cm(-)(1)). These results, combined with estimates for the double
      exchange and the vibronic coupling contributions of the dimer sub-site of the
      tetramer, lead to a delocalized S(t) = (9)/(2) spin ground state for the mixed
      valence dimer in the tetramer. Thus, the decrease in the covalency, hence the
      superexchange pathway associated with changing the bridging mode of the sulfides
      from micro(2) to micro(3) on going from the dimer to the tetramer, significantly
      contributes to the delocalization of the excess electron over the dimer sub-site
      in the tetramer.

PMID- 11456548
TI  - Why is there an "inert" metal center in the active site of nitrile hydratase?
      Reactivity and ligand dissociation from a five-coordinate Co(III) nitrile
      hydratase model.
AB  - To determine how a substitutionally inert metal can play a catalytic role in the
      metalloenzyme nitrile hydratase (NHase), a reactive five-coordinate Co(III)
      thiolate complex ([Co(III)(S(2)(Me2)N(3)(Pr,Pr))](PF(6)) (1)) that resembles the
      active site of cobalt containing nitrile hydratase (Co NHase) was prepared. This
      was screened for reactivity, by using low-temperature electronic absorption
      spectroscopy, toward a number of biologically relevant "substrates". It was
      determined 1 will react with azide, thiocyanate, and ammonia, but is unreactive
      toward nitriles, NO, and butyrate. Substrate-bound 1 has similar spectroscopic
      and structural properties as [Co(III)(ADIT(2))](PF(6)) (2). Complex 2 is a six
      coordinate Co(III) complex containing cis-thiolates and imine nitrogens, and has
      properties similar to the cobalt center of Co NHase. Substrate binding to 1 is
      reversible and temperature-dependent, allowing for the determination of the
      thermodynamic parameters of azide and thiocyanate binding and the rates of ligand
      dissociation. Azide and thiocyanate bind trans to a thiolate, and with similar
      entropies and enthalpies (thiocyanate: DeltaH = -7.5 +/- 1.1 kcal/mol, DeltaS = 
      17.2 +/- 3.2 eu; azide: DeltaH = -6.5 +/- 1.0 kcal/mol, DeltaS = -12.6 +/- 2.4
      eu). The rates of azide and thiocyanate displacement from the metal center are
      also comparable to one another (k(d) = (7.22 +/- 0.04) x 10(-)(1) s(-)(1) for
      thiocyanate and k(d) = (2.14 +/- 0.50) x 10(-)(2) s(-)(1) for azide), and are
      considerably faster than one would expect for a low-spin d(6) six-coordinate
      Co(III) complex. These rates are comparable to those of an analogous Fe(III)
      complex, demonstrating that Co(III) and Fe(III) react at comparable rates when in
      this ligand environment. This study therefore indicates that ligand displacement
      from a low-spin Co(III) center in a ligand environment that resembles NHase is
      not prohibitively slow so as to disallow catalytic action in nonredox active
      cobalt metalloenzymes.

PMID- 11456551
TI  - Conformational analysis of a flexible oligosaccharide using residual dipolar
      couplings.
AB  - We present a new approach to the analysis of the conformational and the motional
      properties of an oligosaccharide, methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha
      D-mannopyranoside. The approach relies on an order matrix analysis of residual
      dipolar couplings in the solution state. By combining a number of different types
      of couplings, (1)D(CH), (2)D(CH), and D(HH), an order matrix is solved for each
      ring of the trimannoside. The resulting order parameters indicate the internal
      motion at the alpha (1,3) linkage to be limited, while significant motion is
      suggested at the alpha (1,6) linkage. Two structures for the trimannoside were
      determined by aligning the order tensor principal axes obtained from two
      different orienting media, bicelles and phage. The very similar conformations at
      the alpha (1,3) linkage of these two structures confirm that the internal motion
      at the alpha (1,3) linkage is small and the conformation is a good representation
      of a single preferred structure. The different conformations at the alpha (1,6)
      linkage suggest that the motional amplitudes are large and the conformations must
      be viewed as virtual conformers. Compared with traditional NMR methods, data
      acquisition is easy and data analysis is straightforward.

PMID- 11456553
TI  - Self-assembled columns of stacked lipid bilayers mediated by metal ion
      recognition.

PMID- 11456557
TI  - Aplydactone, a new sesquiterpenoid with an unprecedented carbon skeleton from the
      sea hare Aplysia dactylomela, and its cargill-like rearrangement.

PMID- 11456558
TI  - Synthesis of crotonyl-oxyCoA: a mechanistic probe of the reaction catalyzed by
      enoyl-CoA hydratase.

PMID- 11456559
TI  - An efficient new route to plasmenyl-type lipids: synthesis and cytotoxicity of a
      plasmenylcholine analogue of the antitumor ether lipid ET-18-OMe.

PMID- 11456561
TI  - Engineering a ligand binding pocket into a four-helix bundle protein cytochrome
      b(562).

PMID- 11456562
TI  - A new type of helix pattern in polyalanine peptide.

PMID- 11456563
TI  - Structure/energy correlation of bowl depth and inversion barrier in corannulene
      derivatives: combined experimental and quantum mechanical analysis.
AB  - Synthesis of a series of corannulene derivatives with varying bowl depths has
      allowed for a study correlating the structure (bowl depth) and the energy of bowl
      inversion. Substituents placed in the peri positions are repulsive and flatten
      the bowl, thus causing a decrease in the bowl inversion barrier. Conversely,
      annelation across the peri positions causes a deepening of the bowl, thus an
      increase in the bowl inversion barrier. Barriers between 8.7 and 17.3 kcal/mol
      have been measured, and their structures have been calculated using a variety of
      ab initio methods. The energy profile of an individual corannulene derivative is
      assumed to fit a mixed quartic/quadratic function from which an empirical
      correlation of bowl depth and inversion barrier that follows a quartic function
      is derived. Structure/energy correlations of this type speak broadly of the
      nature of enzymatic and catalytic activation of substrates.

PMID- 11456564
TI  - Synthesis of peptides and proteins without cysteine residues by native chemical
      ligation combined with desulfurization.
AB  - The highly chemoselective reaction between unprotected peptides bearing an N
      terminal Cys residue and a C-terminal thioester enables the total and semi
      synthesis of complex polypeptides. Here we extend the utility of this native
      chemical ligation approach to non-cysteine containing peptides. Since alanine is
      a common amino acid in proteins, ligation at this residue would be of great
      utility. To achieve this goal, a specific alanine residue in the parent protein
      is replaced with cysteine to facilitate synthesis by native chemical ligation.
      Following ligation, selective desulfurization of the resulting unprotected
      polypeptide product with H(2)/metal reagents converts the cysteine residue to
      alanine. This approach, which provides a general method to prepare alanyl
      proteins from their cysteinyl forms, can be used to chemically synthesize a
      variety of polypeptides, as demonstrated by the total chemical syntheses of the
      cyclic antibiotic microcin J25, the 56-amino acid streptococcal protein G B1
      domain, and a variant of the 110-amino acid ribonuclease, barnase.

PMID- 11456565
TI  - Predominant 1,2-insertion of styrene in the Pd-catalyzed alternating
      copolymerization with carbon monoxide.
AB  - The regioselectivity of styrene insertion to an acyl-Pd bond was studied by NMR
      in (i) a stoichiomeric reaction and (ii) a copolymerization with CO. In the
      stoichiometric reaction of styrene with [(CH(3)CO)Pd(CH(3)CN)[(R,S)
      BINAPHOS]].[B[3,5-(CF(3))(2)C(6)H(3)](4)], both 1,2- and 2,1-products were given.
      To mimic the real polymerization conditions, a polyketone-substituted complex
      [[CH(3)(CH(2)CHCH(3)CO)(n)]Pd[(R,S)-BINAPHOS]].[B(3,5-(CF(3))(2)C(6)H(3))(4)] (n
      approximately 14) was prepared. When this polymer-attached Pd species was treated
      with styrene, the 1,2-insertion product was the only detectable species. Thus,
      exclusive 1,2-insertion is demonstrated to be responsible for the styrene-CO
      copolymerization, in sharp contrast to the predominant 2,1-insertion with
      conventional nitrogen ligands. Chain-end analysis revealed that beta-hydride
      elimination took place from the 2,1-complex but not from the 1,2-complex. Thus,
      once 2,1-insertion occurs, rapid beta-hydride elimination proceeds to terminate
      the polymerization, as is common to the other phosphorus-ligand systems. The
      resulting Pd-H species re-initiates the copolymerization, as was proven by MALDI
      TOF mass analysis of the product copolymers.

PMID- 11456566
TI  - Kinetic resolution using enantioimpure catalysts: mechanistic considerations of
      complex rate laws.
AB  - Kinetic resolutions in which the reactions exhibit complex rate laws are
      discussed. When enantioimpure catalysts are employed, a conversion-dependent
      selectivity factor k(rel) may in some cases be observed due to "kinetic
      partitioning" of catalysts within a reaction network. Both asymmetric
      amplifications and depletions may be observed, and the effects are separate from
      and may in some cases be superimposed on-the classic nonlinear effect due to
      catalyst interactions as those predicted by Kagan's ML(n) models. Consideration
      of the conversion dependence of the selectivity factor using enantioimpure
      catalysts reveals significant detail about the reaction mechanism for the
      enantiopure case and may offer insights for practical application of kinetic
      resolution. Examples from the literature are analyzed in the context of kinetic
      partitioning.

PMID- 11456567
TI  - Isolation and structure elucidation of Chlorofusin, a novel p53-MDM2 antagonist
      from a Fusarium sp.
AB  - Wild-type p53 plays a crucial role in the prevention of cancer. Since dysfunction
      of p53 can be caused by increased levels of the protein MDM2, small molecules
      which antagonize the interaction between these two proteins have potential in
      cancer therapy. The discovery and structure determination of a fungal metabolite,
      chlorofusin, which antagonizes the p53/MDM2 interaction are reported.

PMID- 11456568
TI  - Total syntheses of thiocoraline and BE-22179 and assessment of their DNA binding
      and biological properties.
AB  - Full details of the total syntheses of thiocoraline (1) and BE-22179 (2), C(2)
      symmetric bicyclic octadepsipeptides possessing two pendant 3-hydroxyquinoline
      chromophores, are described in which their relative and absolute stereochemistry
      were established. Key elements of the approach include the late-stage
      introduction of the chromophore, symmetrical tetrapeptide coupling,
      macrocyclization of the 26-membered octadepsipeptide conducted at the single
      secondary amide site following disulfide formation, and a convergent assemblage
      of the tetradepsipeptide with introduction of the labile thiol ester linkage in
      the final coupling reaction under near racemization free conditions. By virtue of
      the late-stage introduction of the chromophore and despite the challenges this
      imposes on the synthesis, this approach provides ready access to a range of key
      chromophore analogues. Thiocoraline and BE-22179 were shown to bind to DNA by
      high-affinity bisintercalation analogous to echinomycin, but with little or no
      perceptible sequence selectivity. Both 1 and 2 were found to exhibit exceptional
      cytotoxic activity (IC(50) = 200 and 400 pM, respectively, L1210 cell line)
      comparable to echinomycin and one analogue, which bears the luzopeptin
      chromophore, was also found to be a potent cytotoxic agent.

PMID- 11456569
TI  - Synthesis of ketonylplatinum(III) dinuclear complexes: observation of the
      competitive radical vs electrophilic displacement in Pt(III)-promoted C-H bond
      activation of ketones.
AB  - New ketonylplatinum(III) dinuclear complexes
      [Pt(2)((CH(3))(3)CCONH)(2)(NH(3))(4)(CH(2)COPh)](NO(3))(3) (4),
      [Pt(2)((CH(3))(3)CCONH)(2)(NH(3))(4)(CH(CH(3))COC(2)H(5))](NO(3))(3) (5), and
      [Pt(2)((CH(3))(3)CCONH)(2)(NH(3))(4)(CH(2)COCH(2)COCH(3))](NO(3))(3) (6) were
      prepared by treatment of platinum blue complex
      [Pt(4)(NH(3))(8)((CH(3))(3)CCONH)(4)](NO(3))(5) (2) with acetophenone, 3
      pentanone, and acetylacetone, respectively, in the presence of concentrated
      HNO(3). The structures of complexes 4 and 6 have been confirmed by X-ray
      diffraction analysis, which revealed that the C-H bonds of the methyl groups in
      acetophenone and acetylacetone have been cleaved and Pt(III)-C bonds are formed.
      Formation of diketonylplatinum(III) complex 6 provides a novel example of the C-H
      bond activation not at the central alpha-C-H but at the terminal methyl of
      acetylacetone. Reaction with butanone having unsymmetrical alpha-H atoms led to
      two types of ketonylplatinum(III) complexes
      [Pt(2)((CH(3))(3)CCONH)(2)(NH(3))(4)(CH(CH(3))COCH(3))](NO(3))(3) (7a) and
      [Pt(2)((CH(3))(3)CCONH)(2)(NH(3))(4)(CH(2)COCH(2)CH(3))](NO(3))(3) (7b) at a
      molar ratio of 1.7 to 1 corresponding to the C-H bond activation of methylene and
      methyl groups, respectively. Use of 3-methyl-2-butanone instead of butanone gave
      complex [Pt(2)((CH(3))(3)CCONH)(2)(NH(3))(4)(CH(2)COCH(CH(3))(2))](NO(3))(3) (8)
      as a sole product via C-H bond activation in the alpha-methyl group. The
      reactivity of the ketonylplatinum(III) dinuclear complexes toward nucleophiles,
      such as H(2)O and HNEt(2), was examined. The alpha-hydroxyl- and alpha-amino
      substituted ketones were generated in the reactions of
      [Pt(2)((CH(3))(3)CCONH)(2)(NH(3))(4)(CH(2)COCH(3))](NO(3))(3) (1), 5, and a
      mixture of 7a and 7b with water and amine, which indicates that the carbon atom
      in the ketonyl group bound to the Pt(III) atom can receive a nucleophilic attack.
      The high electrophilicity of the ketonylplatinum(III) complexes can be accounted
      for by the high electron-withdrawing ability of the platinum(III) atom. A
      competition between the radical and electrophilic displacement pathways was
      observed directly in the C-H bond activation reaction with butanone giving
      complexes 7a and 7b. Addition of a radical trapping agent suppressed the radical
      pathway and gave complex 7b as the predominant product. On the contrary, 7a was
      formed as the main product when the reaction solution was irradiated by mercury
      lamp light. These results together with other mechanistic studies demonstrate
      that complex 7a was produced via a radical process, whereas complex 7b is
      produced via electrophilic displacement of a proton by the Pt(III) atom. The
      competitive processes were further observed in the reactions of platinum blue
      complex 2 with a mixture of acetone and 3-pentanone in the presence of HNO(3).
      The relative molar ratio of acetonyl complex 1 to pentanoyl complex 5 was 3 to 1
      under room light, whereas formation of complex 5 was almost suppressed when the
      reaction was carried out in the dark with the addition of a radical trapping
      agent.

PMID- 11456570
TI  - Characterization of the copper-sulfur chromophores in nitrous oxide reductase by
      resonance raman spectroscopy: evidence for sulfur coordination in the catalytic
      cluster.
AB  - Nitrous oxide reductase (N(2)OR) from Pseudomonas stutzeri, a dimeric enzyme with
      a canonical metal ion content of at least six Cu ions per subunit, contains two
      types of multinuclear copper sites: Cu(A) and Cu(Z). An electron-transfer role
      for the dinuclear Cu(A) site is indicated based on its similarity to the Cu(A)
      site in cytochrome c oxidase (CcO), a dicysteinate-bridged, mixed-valence
      cluster. The Cu(Z) site is the catalytic site, which had long been thought to
      have novel spectroscopic properties. However, the low-energy electronic
      transitions and resonance Raman features attributable to Cu(Z) have been
      difficult to reconcile with a lack of conserved cysteine residues in standard
      alignments of N(2)OR sequences, other than those associated with the Cu(A) site.
      Recent evidence indicates that nitrous oxide reductase contains acid-labile
      sulfide and that this sulfide is a constituent of the Cu(Z) site (Rasmussen, T.;
      Berks, B. C.; Sanders-Loehr, J.; Dooley, D. M.; Zumft, W. G.; Thomson, A. J.
      Biochemistry 2000, 39, 12753-12756). We have used resonance Raman (RR)
      spectroscopy to selectively probe the Cu(A) and Cu(Z) sites of N(2)OR in three
      oxidation states (oxidized, semireduced, and reduced) as well as Cu(A)-only and
      Cu(Z)-only variants. The Cu(A) (mixed-valence, also designated as A(mv)) RR
      spectrum exhibits 10 vibrational modes between 220 and 410 cm(-1), with >1-cm(-1)
      (34)S isotope shifts that sum to -16.6 cm(-1). Many of these modes are also
      sensitive to (65)Cu and (15)N(His) and, thus, can be assigned to coupling of the
      Cu-S stretch, nu(Cu-S), with cysteine and histidine vibrations of the
      Cu(2)Cys(2)His(2) core. The RR spectrum of the Cu(Z) site (Z(ox)) reveals a novel
      Cu-sulfur chromophore with four S isotope-sensitive modes at 293, 347, 352, and
      408 cm(-1), with a total (34)S shift of -19.9 cm(-)(1). The magnitude of the S
      isotope shifts and wide spread of perturbed frequencies are similar to those
      observed in Cu(A) and therefore suggest a sulfur-bridged cluster in Z(ox). The
      Z(ox) site has its nu(Cu-S)-containing modes at higher energy and exhibits less
      mixing with ligand deformations, compared to Cu(A). Reduction by dithionite
      produces a mixed-valence Cu(Z) site (Z(mv)) with six S isotope-sensitive RR modes
      between 282 and 382 cm(-1) and a total (34)S-shift of -16.9 cm(-1). The
      observation of a nearly identical RR spectrum in the C622D variant of N(2)OR,
      which lacks one of the conserved Cu(A) Cys residues, establishes that Cu-S
      vibrations observed in this variant arise from the Z(mv) site. Furthermore, none
      of the features assigned to Cu(Z) are detected in a second variant that contains
      only Cu(A). Therefore the resonance Raman spectra reported here provide
      compelling evidence for a unique Cu-S cluster in the catalytic site of nitrous
      oxide reductase.

PMID- 11456571
TI  - Superelectrophilic tetrakis(carbonyl)palladium(II)- and -platinum(II)
      undecafluorodiantimonate(V), [Pd(CO)4][Sb(2)F(11)]2 and [Pt(CO)4][Sb(2)F(11)]2:
      syntheses, physical and spectroscopic properties, their crystal, molecular, and
      extended structures, and density functional calculations: an experimental,
      computational, and comparative study .
AB  - The salts [M(CO)(4)][Sb(2)F(11)](2), M = Pd, Pt, are prepared by reductive
      carbonylation of Pd[Pd(SO(3)F)(6)], Pt(SO(3)F)(4) or PtF(6) in liquid SbF(5), or
      HF-SbF(5). The resulting moisture-sensitive, colorless solids are thermally
      stable up to 140 degrees C (M = Pd) or 200 degrees C (M = Pt). Their thermal
      decompositions are studied by differential scanning calorimetry (DSC). Single
      crystals of both salts are suitable for an X-ray diffraction study at 180 K. Both
      isostructural salts crystallize in the monoclinic space group P2(1)/c (No. 14).
      The unit cell volume of [Pt(CO)(4)][Sb(2)F(11)](2) is smaller than that of
      [Pd(CO)(4)][Sb(2)F(11)](2) by about 0.4%. The cations [M(CO)(4)](2+), M = Pd, Pt,
      are square planar with only very slight angular and out-of-plane deviations from
      D(4)(h)() symmetry. The interatomic distances and bond angles for both cations
      are essentially identical. The [Sb(2)F(11)](-) anions in
      [M(CO)(4)][Sb(2)F(11)](2,) M = Pd, Pt, are not symmetry-related, and both pairs
      differ in their Sb-F-Sb bridge angles and their dihedral angles. There are in
      each salt four to five secondary interionic C- -F contacts per CO group. Of
      these, two contacts per CO group are significantly shorter than the sum of the
      van der Waals radii by 0.58 - 0.37 A. In addition, structural, and spectroscopic
      details of recently synthesized [Rh(CO)(4)][Al(2)Cl(7)] are reported. The cations
      [Rh(CO)(4)](+) and [M(CO)(4)](2+), M = Pd, Pt, are characterized by IR and Raman
      spectroscopy. Of the 16 vibrational modes (13 observable, 3 inactive) 10 (Pd, Pt)
      or 9 (Rh), respectively, are found experimentally. The vibrational assignments
      are supported by DFT calculations, which provide in addition to band positions
      also intensities of IR bands and Raman signals as well as internal force
      constants for the cations. (13)C NMR measurements complete the characterization
      of the square planar metal carbonyl cations. The extensive characterization of
      [M(CO)(4)][Sb(2)F(11)](2), M = Pd, Pt, reported here, allows a comparison to
      linear and octahedral [M(CO)(n)()][Sb(2)F(11)](2) salts [M = Hg (n = 2); Fe, Ru,
      Os (n = 6)] and their derivatives, which permit a deeper understanding of M-CO
      bonding in the solid state for superelectrophilic cations with [Sb(2)F(11)](-) or
      [SbF(6)](-) as anions.

PMID- 11456572
TI  - C-D(0) (D(0) = pi-donor, F) Cleavage in H(2)C=CH(D(0)) by (Cp(2)ZrHCl)(n):
      mechanism, agostic fluorines, and a carbene of Zr(IV).
AB  - Consistent with the C-O cleavage behavior of vinyl ethers, vinyl fluoride reacts
      with Cp(2)ZrHCl to give Cp(2)ZrFCl and C(2)H(4) as primary products. DFT (B3PW91)
      calculations show this reaction to be highly exoenergetic (-55 kcal/mol), and
      reveal a sigma-bond metathesis mechanism to be unfavorable compared to a Zr-H
      addition across the C=C bond, with regiochemistry placing F on C(beta) of the
      resulting fluoroethyl ligand. beta-F elimination (onto Zr) then completes the
      reaction. There is no eta(2)-olefin intermediate on the reaction path. DFT
      calculations seeking the energy and structure of the two carbenes
      Cp(2)ZrHCl[CF(CH(3))] and Cp(2)ZrFCl[CH(CH(3))] are also described.

PMID- 11456573
TI  - Thermal activation of hydrocarbon C-H bonds by tungsten alkylidene complexes.
AB  - Thermal activation of CpW(NO)(CH(2)CMe(3))(2) (1) in neat hydrocarbon solutions
      transiently generates the neopentylidene complex, CpW(NO)(=CHCMe(3)) (A), which
      subsequently activates solvent C-H bonds. For example, the thermolysis of 1 in
      tetramethylsilane and perdeuteriotetramethylsilane results in the clean formation
      of CpW(NO)(CH(2)CMe(3))(CH(2)SiMe(3)) (2) and
      CpW(NO)(CHDCMe(3))[CD(2)Si(CD(3))(3)] (2-d(12)), respectively, in virtually
      quantitative yields. The neopentylidene intermediate A can be trapped by PMe(3)
      to obtain CpW(NO)(=CHCMe(3))(PMe(3)) in two isomeric forms (4a-b), and in
      benzene, 1 cleanly forms the phenyl complex CpW(NO)(CH(2)CMe(3))(C(6)H(5)) (5).
      Kinetic and mechanistic studies indicate that the C-H activation chemistry
      derived from 1 proceeds through two distinct steps, namely, (1) rate-determining
      intramolecular alpha-H elimination of neopentane from 1 to form A and (2) 1,2-cis
      addition of a substrate C-H bond across the W=C linkage in A. The thermolysis of
      1 in cyclohexane in the presence of PMe(3) yields 4a-b as well as the olefin
      complex CpW(NO)(eta(2)-cyclohexene)(PMe(3)) (6). In contrast, methylcyclohexane
      and ethylcyclohexane afford principally the allyl hydride complexes
      CpW(NO)(eta(3)-C(7)H(11))(H) (7a-b) and CpW(NO)(eta(3)-C(8)H(13))(H) (8a-b),
      respectively, under identical experimental conditions. The thermolysis of 1 in
      toluene affords a surprisingly complex mixture of six products. The two major
      products are the neopentyl aryl complexes, CpW(NO)(CH(2)CMe(3))(C(6)H(4)-3-Me)
      (9a) and CpW(NO)(CH(2)CMe(3))(C(6)H(4)-4-Me) (9b), in approximately 47 and 33%
      yields. Of the other four products, one is the aryl isomer of 9a-b, namely,
      CpW(NO)(CH(2)CMe(3))(C(6)H(4)-2-Me) (9c) ( approximately 1%). The remaining three
      products all arise from the incorporation of two molecules of toluene; namely,
      CpW(NO)(CH(2)C(6)H(5))(C(6)H(4)-3-Me) (11a; approximately 12%),
      CpW(NO)(CH(2)C(6)H(5))(C(6)H(4)-4-Me) (11b; approximately 6%), and
      CpW(NO)(CH(2)C(6)H(5))(2) (10; approximately 1%). It has been demonstrated that
      the formation of complexes 10 and 11a-b involves the transient formation of
      CpW(NO)(CH(2)CMe(3))(CH(2)C(6)H(5)) (12), the product of toluene activation at
      the methyl position, which reductively eliminates neopentane to generate the C-H
      activating benzylidene complex CpW(NO)(=CHC(6)H(5)) (B). Consistently, the
      thermolysis of independently prepared 12 in benzene and benzene-d(6) affords
      CpW(NO)(CH(2)C(6)H(5))(C(6)H(5)) (13) and CpW(NO)(CHDC(6)H(5))(C(6)D(5)) (13
      d(6)), respectively, in addition to free neopentane. Intermediate B can also be
      trapped by PMe(3) to obtain the adducts CpW(NO)(=CHC(6)H(5))(PMe(3)) (14a-b) in
      two rotameric forms. From their reactions with toluene, it can be deduced that
      both alkylidene intermediates A and B exhibit a preference for activating the
      stronger aryl sp(2) C-H bonds. The C-H activating ability of B also encompasses
      aliphatic substrates as well as it reacts with tetramethylsilane and cyclohexanes
      in a manner similar to that summarized above for A. All new complexes have been
      characterized by conventional spectroscopic methods, and the solid-state
      molecular structures of 4a, 6, 7a, 8a, and 14a have been established by X-ray
      diffraction methods.

PMID- 11456574
TI  - A minimal peptide scaffold for beta-turn display: optimizing a strand position in
      disulfide-cyclized beta-hairpins.
AB  - Phage display of peptide libraries has become a powerful tool for the evolution
      of novel ligands that bind virtually any protein target. However, the rules
      governing conformational preferences in natural peptides are poorly understood,
      and consequently, structure-activity relationships in these molecules can be
      difficult to define. In an effort to simplify this process, we have investigated
      the structural stability of 10-residue, disulfide-constrained beta-hairpins and
      assessed their suitability as scaffolds for beta-turn display. Using disulfide
      formation as a probe, relative free energies of folding were measured for 19
      peptides that differ at a one strand position. A tryptophan substitution promotes
      folding to a remarkable degree. NMR analysis confirms that the measured energies
      correlate well with the degree of beta-hairpin structure in the disulfide
      cyclized peptides. Reexamination of a subset of the strand substitutions in
      peptides with different turn sequences reveals linear free energy relationships,
      indicating that turns and strand-strand interactions make independent, additive
      contributions to hairpin stability. Significantly, the tryptophan strand
      substitution is highly stabilizing with all turns tested, and peptides that
      display model turns or the less stable C'-C' ' turn of CD4 on this tryptophan
      "stem" are highly structured beta-hairpins in water. Thus, we have developed a
      small, structured beta-turn scaffold, containing only natural L-amino acids, that
      may be used to display peptide libraries of limited conformational diversity on
      phage.

PMID- 11456575
TI  - Field- and phage-induced dipolar couplings in a homodimeric DNA quadruplex:
      relative orientation of G.(C-A) triad and G-tetrad motifs and direct
      determination of C2 symmetry axis orientation.
AB  - We present a new NMR procedure for determining the three-dimensional fold of C2
      symmetric nucleic acid homodimers that relies on long-range orientational
      constraints derived from the measurement of two independent sets of residual
      dipolar couplings under two alignment conditions. The application is demonstrated
      on an (15)N/(13)C-enriched deoxyoligonucleotide sequence, d(G-G-G-T-T-C-A-G-G),
      shown previously to dimerize into a quadruplex in solution and form a pair of
      G.(C-A) triads and G-G-G-G tetrads (G-tetrad) motifs. One-bond (1)H-(15)N
      ((1)D(NH)) and (1)H-(13)C ((1)D(CH)) residual dipolar couplings have been
      measured between nuclei in the bases of these motifs using bacteriophage as an
      ordering medium, and under direct magnetic field alignment (800 MHz). By
      combining the two dipolar data sets in an order matrix analysis, the orientation
      of the G.(C-A) triad relative to the G-tetrad within a contiguous monomeric unit
      can directly be determined, even in the presence of interstrand/intrastrand NOE
      ambiguity. We further demonstrate that the orientation of the C2-axis of
      molecular symmetry in the homodimer relative to the G.(C-A) triad and G-tetrad
      motifs can unambiguously be determined using the two sets of independent dipolar
      coupling measurements. The three-dimensional fold of the homodimer determined
      using this procedure is very regular and in excellent agreement with a previously
      determined high-resolution NOE-based NMR structure, where interstrand/intrastrand
      NOEs were treated as ambiguous and where noncrystallographic symmetry constraints
      were implicitly imposed during the structure calculation.

PMID- 11456576
TI  - Long live vinylidene! A new view of the H(2)C=C: --> HC triple bond CH
      rearrangement from ab initio molecular dynamics.
AB  - We present complete active space self-consistent field (CASSCF) ab initio
      molecular dynamics (AIMD) simulations of the preparation of the metastable
      species vinylidene, and its subsequent, highly exothermic isomerization to
      acetylene, via electron removal from vinylidene anion (D(2)C=C(-) --> D(2)C=C: -
      > DC triple bond CD). After equilibrating vinylidene anion-d(2) at either 600 +/-
      300 K (slightly below the isomerization barrier) or 1440 K +/- 720 K (just above
      the isomerization barrier), we remove an electron to form a vibrationally excited
      singlet vinylidene-d(2) and follow its dynamical evolution for 1.0 ps.
      Remarkably, we find that none of the vinylidenes equilibrated at 600 K and only
      20% of the vinylidenes equilibrated at 1440 K isomerized, suggesting average
      lifetimes >1 ps for vibrationally excited vinylidene-d(2). Since the anion and
      neutral vinylidene are structurally similar, and yet extremely different
      geometrically from the isomerization transition state (TS), neutral vinylidene is
      not formed near the TS so that it must live until it has sufficient instantaneous
      kinetic energy in the correct vibrational mode(s). The origin of the delay is
      explained via both orbital rearrangement and intramolecular vibrational energy
      redistribution (IVR) effects. Unique signatures of the isomerization dynamics are
      revealed in the anharmonic vibrational frequencies extracted from the AIMD, which
      should be observable by ultrafast vibrational spectroscopy and in fact are
      consistent with currently available experimental spectra. Most interestingly, of
      those trajectories that did isomerize, every one of them violated conventional
      transition-state theory by recrossing back to vinylidene multiple times, against
      conventional notions that expect highly exothermic reactions to be irreversible.
      The dynamical motion responsible for the multiple barrier recrossings involves
      strong mode-coupling between the vinylidene CD(2) rock and a local acetylene DCC
      bend mode that has been recently observed experimentally. The multiple barrier
      recrossings can be used, via a generalized definition of lifetime, to reconcile
      extremely disparate experimental estimates of vinylidene's lifetime (differing by
      at least 6 orders of magnitude). Last, a caveat: These results are constrained by
      the approximations inherent in the simulation (classical nuclear motion, neglect
      of rotation-vibration coupling, and restriction to C(s) symmetry); refinement of
      these predictions may be necessary when more exact simulations someday become
      feasible.

PMID- 11456577
TI  - [(13)C,(13)C]- and [(13)C,(1)H]-TROSY in a triple resonance experiment for ribose
      base and intrabase correlations in nucleic acids.
AB  - A novel TROSY (transverse relaxation-optimized spectroscopy) element is
      introduced that exploits cross-correlation effects between (13)C-(13)C dipole
      dipole (DD) coupling and (13)C chemical shift anisotropy (CSA) of aromatic ring
      carbons. Although these (13)C-(13)C effects are smaller than the previously
      described [(13)C,(1)H]-TROSY effects for aromatic (13)C-(1)H moieties, their
      constructive use resulted in further transverse relaxation-optimization by up to
      15% for the resonances in a 17 kDa protein-DNA complex. As a practical
      application, two- and three-dimensional versions of the HCN triple resonance
      experiment for obtaining ribose-base and intrabase correlations in the
      nucleotides of DNA and RNA (Sklenar, V.; Peterson, R. D.; Rejante, M. R.; Feigon,
      J. J. Biomol. NMR 1993, 3, 721-727) have been implemented with [(13)C,(1)H]- and
      [(13)C,(13)C]-TROSY elements to reduce the rate of transverse relaxation during
      the polarization transfers between ribose (13)C1' and base (15)N1/9 spins, and
      between (13)C6/8 and N1/9 within the bases. The resulting TROSY-HCN experiment is
      user-friendly, with a straightforward, robust experimental setup. Compared to the
      best previous implementations of the HCN experiment, 2-fold and 5-fold
      sensitivity enhancements have been achieved for ribose-base and intrabase
      connectivities, respectively, for (13)C,(15)N-labeled nucleotides in structures
      with molecular weights of 10 and 17 kDa. TROSY-HCN experiments should be
      applicable also with significantly larger molecular weights. By using modified
      TROSY-HCN schemes, the origins of the sensitivity gains have been analyzed.

PMID- 11456578
TI  - Ferroelectric valence transition and phase diagram of a series of charge-transfer
      complexes of 4,4'-dimethyltetrathiafulvalene and tetrahalo-p-benzoquinones.
AB  - Variation of the ferroelectric phase transition has been investigated for a
      series of isomorphous donor (D)-acceptor (A) charge-transfer complexes composed
      of 4,4'-dimethyltetrathiafulvalene (DMTTF) and tetrahalo-p-benzoquinones by
      measurements of dielectric susceptibility, X-ray diffraction, and infrared
      molecular vibrational spectra. The neutral-ionic phase transition of DMTTF-p
      chloranil at 65 K accompanies a dielectric peak anomaly associated with the DA
      stack dimerization. Successive halogen replacement by bromine in the component
      tetrahalo-p-benzoquinone molecule expands the lattice along the DA stack of the
      DMTTF complex, and reduces the critical temperature steeply toward zero
      temperature in an analogous way to the critical behavior of quantum
      ferroelectrics. The 2,6-dibromo-substituted compound showing the behavior of the
      quantum paraelectricity is located in the immediate vicinity of the quantum
      critical point of this phase diagram as signified also by enhancement of the
      ionicity, the dielectric susceptibility, and the dynamical dimeric distortion at
      the lowest temperature.

PMID- 11456579
TI  - The ultraviolet photochemistry of phenylacetylene and the enthalpy of formation
      of 1,3,5-hexatriyne.
AB  - The ultraviolet photochemistry of phenylacetylene was studied in a molecular beam
      at 193 nm. The only primary photofragments observed were HCCH (acetylene) and
      C(6)H(4). Some of the C(6)H(4) molecules were found to decompose to 1,3,5
      hexatriyne and molecular hydrogen. An enthalpy of formation of DeltaH(f) < or =
      160 +/- 4 kcal mol(-1) was determined for 1,3,5-hexatriyne from the energetic
      threshold for this process. This experimentally determined value agrees well with
      our ab initio calculations performed at the G2 level of theory. Angular
      distribution measurements for the HCCH + C(6)H(4) channel yielded an isotropic
      distribution and were attributed to a long-lived intermediate and ground-state
      dissociation. An exhaustive search yielded no evidence for the phenyl + ethynyl
      or the atomic hydrogen elimination channels even though these were observed in
      the pyrolytic studies of phenylacetylene [Hofmann, J.; Zimmermann, G.; Guthier,
      K.; Hebgen, P.; Homann, K. H. Liebigs Ann. 1995, 631, 1995. Guthier, K.; Hebgen,
      P.; Hofmann, K. H.; Zimmermann, G. Liebigs Ann. 1995, 637, 1995].

PMID- 11456580
TI  - Molecular dynamics study on hydrophobic effects in aqueous urea solutions.
AB  - Hydrophobic effects in aqueous urea were analyzed by molecular dynamics
      simulations. The contribution of solvents to the potential of mean force between
      two methane molecules was calculated by using molecular dynamics simulations and
      was compared with the solubility data of hydrocarbons in aqueous urea. Both the
      simulation results and the solubility data indicated that urea stabilizes methane
      methane association. The stabilization was due to increasing the solvation free
      energies of small hydrocarbons such as methane by addition of urea. The solvation
      free energies of larger hydrocarbons, on the other hand, are decreased by
      addition of urea. This effect of the solute size on hydrophobic free energies in
      aqueous urea was also analyzed by using molecular dynamics simulations by means
      of division of the solvation process into two parts: the cavity formation and the
      introduction of the solute-solvent attractive interactions. In the cavity
      formation, urea increased hydrophobic free energies, and in the introduction of
      the solute-solvent attractive interactions, urea decreased hydrophobic free
      energies. The influence of urea on hydrophobic free energies was determined by
      the balance of effects of the two parts of the solvation process.

PMID- 11456581
TI  - Intracluster anionic oligomerization of acrylic ester molecules initiated by
      electron transfer from an alkali metal atom.
AB  - Stabilities and intracluster reactions have been investigated by photoionization
      mass spectrometry for clusters composed of an alkali metal atom (M; Na and K) and
      acrylic ester molecules, CH(2)=CHCO(2)R, such as methyl acrylate (MA; R = CH(3))
      and ethyl acrylate (EA; R = C(2)H(5)). The following two features are commonly
      observed in the photoionization mass spectra of M(CH(2)=CHCO(2)R)(n): (1) The ion
      with n = 3 is clearly observed as a magic number. (2) Fragmented cluster ions
      with the loss of ROH, [M(CH(2)=CHCO(2)R)(n) - ROH] are detected only for n = 3.
      These features are both explained by an intracluster oligomerization reaction
      initiated by electron transfer from the metal atoms. The magic number trimer is
      concluded to have the stable structure of cyclohexane derivatives as a result of
      oligomerization. The fragmentation reaction is explained by Dieckmann cyclization
      after anionic oligomerization to produce another isomer of the trimer. The
      intracluster electron transfer is also supported by theoretical calculation for
      Na(MA) based on density functional theory.

PMID- 11456582
TI  - Mesoporous titanium phosphate molecular sieves with ion-exchange capacity.
AB  - Novel open framework molecular sieves, titanium(IV) phosphates named, i.e., TCM-7
      and -8 (Toyota Composite Materials, numbers 7 and 8), with new mesoporous
      cationic framework topologies obtained by using both cationic and anionic
      surfactants are reported. The (31)P MAS NMR, UV-visible absorption, and XANES
      data suggest the tetrahedral state of P and Ti, and stabilization of the
      tetrahedral state of Ti in TCM-7/8 is due to the incorporation of phosphorus (at
      Ti/P = 1:1) vis-a-vis the most stable octahedral state of Ti in the pure
      mesoporous TiO(2). Mesoporous TCM-7 and -8 show anion exchange capacity due to
      the framework phosphonium cation and cation exchange capacity due to defective P
      OH groups. The high catalytic activity in the liquid-phase partial oxidation of
      cyclohexene with a dilute H(2)O(2) oxidant supports the tetrahedral coordination
      of Ti in these materials.

PMID- 11456583
TI  - [2+3] Cycloaddition of ethylene to transition metal oxo compounds. analysis of
      density functional results by marcus theory.
AB  - Density functional results on the [2+3] cycloaddition of ethylene to various
      transition metal complexes MO(3)(q) and LMO(3)(q) (q = -1, 0, 1) with M = Mo, W,
      Mn, Tc, Re, and Os and various ligands L = Cp, CH(3), Cl, and O show that the
      corresponding activation barriers DeltaE(double dagger) depend in quadratic
      fashion on the reaction energies DeltaE(0) as predicted by Marcus theory. A
      thermoneutral reaction is characterized by the intrinsic reaction barrier
      DeltaE(0) of 25.1 kcal/mol. Both ethylene [2+3] cycloaddition to an oxo complex
      and the corresponding homolytic M-O bond dissociation are controlled by the
      reducibility of the transition metal center. Indeed, from the easily calculated M
      O bond dissociation energy of the oxo complex one can predict the reaction energy
      DeltaE(0) and hence, by Marcus theory, the corresponding activation barrier
      DeltaE. This allows a systematic representation of more than 25 barriers of [2+3]
      cycloaddition reactions that range from 5 to 70 kcal/mol.

PMID- 11456584
TI  - Time-resolved EPR, fluorescence, and transient absorption studies on
      phthalocyaninatosilicon covalently linked to one or two TEMPO radicals.
AB  - The photophysical properties of tetra-tert-butylphthalocyaninatosilicon (SiPc)
      covalently linked to one or two 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
      radicals (R1, R2) have been studied by fluorescence, transient absorption, and
      time-resolved electron paramagnetic resonance (TREPR) spectroscopies. It is found
      that the fluorescence quantum yields and lifetimes of R1 and R2 decrease compared
      with those of (dihydroxy)SiPc ((dihydroxy)SiPc = 6.8 ns, R1 = 4.7 ns and 42 ps,
      and R2 = 4.7 ns and <30 ps). Transient absorption measurements indicate that the
      lifetime of the excited triplet SiPc is markedly dependent on the number of
      linking TEMPO radicals ((dihydroxy)SiPc = 500 micros, R1 = 7.6 micros, and R2 =
      3.7 micros). These short lifetimes of R1 and R2 in the excited states are
      explained as a result of the interaction with TEMPO changing the ISC between the
      singlet and triplet states to spin-allowed transitions. Quantitative TREPR
      investigations have been carried out for the radical-quartet pair mechanism of R1
      and the photoinduced population transfer of R2. It is determined that the rise
      and decay times of these electron spin polarizations denote the spin-lattice
      relaxation time of the ground state and the lifetime of the excited multiplet
      state, respectively. This study contributes not only to an elucidation of radical
      chromophore interactions but also to a novel approach for controlling magnetic
      properties by photoexcitation.

PMID- 11456585
TI  - A QM/MM study of the racemization of vinylglycolate catalyzed by mandelate
      racemase enzyme.
AB  - The experimentally postulated mechanism for the interconversion between (S)
      vinylglycolate and (R)-vinylglycolate catalyzed by mandelate racemase enzyme
      consists of a two-step quite symmetric process through a dianionic enolic
      intermediate that is formed after the abstraction of the alpha-proton of
      vinylglycolate by a basic enzymatic residue and is then reprotonated by another
      residue. The challenging problem behind this reaction is how the enzyme manages
      to stabilize such an intermediate, that is, how it lowers enough the high pK(a)
      of the alpha-proton for the reaction to take place. The QM/MM simulations
      performed in this paper indicate that catalysis is based on the stabilization of
      the negative charge developed on the substrate along the reaction. We have
      identified three different reaction mechanisms starting from different quasi
      degenerate structures of the substrate-enzyme complex. In two of them the
      stabilizing role is done by means of a catalytic proton transfer that avoids the
      formation of a dianionic intermediate, and they involve six steps instead of the
      two experimentally proposed. On the contrary, the third mechanism passes through
      a dianionic species stabilized by the concerted approach of a protonated
      enzymatic residue during the proton abstraction. The potential energy barriers
      theoretically found along these mechanisms are qualitatively in good agreement
      with the experimental free energy barriers determined for racemization of
      vinylglycolate and mandelate. The theoretical study of the effect of the mutation
      of Glu317 by Gln317 in the kinetics of the reaction reveals the important role in
      the catalysis of the hydrogen bond formed by Glu317 in the native enzyme, as only
      one of the mechanisms, the slower one, is able to produce the racemization in the
      active site of the mutant. However, we have found that this hydrogen bond is not
      an LBHB within our model.

PMID- 11456586
TI  - Potential energy surface crossings and the mechanistic spectrum for
      intramolecular electron transfer in organic radical cations.
AB  - The structure of the potential energy surface for the intramolecular electron
      transfer (IET) of four different model radical cations has been determined by
      using reaction path mapping and conical intersection optimization at the ab
      initio CASSCF level of theory. We show that, remarkably, the calculated paths
      reside in regions of the ground-state energy surface whose structure can be
      understood in terms of the position and properties of a surface crossing between
      the ground and the first excited state of the reactant. Thus, in the
      norbornadiene radical cation and in an analogue compound formed by two
      cyclopentene units linked by a norbornyl bridge, IET proceeds along direct
      overlap and super-exchange concerted paths, respectively, that are located far
      from a sloped conical intersection point and in a region where the excited-state
      and ground-state surfaces are well separated. A second potential energy surface
      structure has been documented for 1,2-diamino ethane radical cation and features
      two parallel concerted (direct) and stepwise (chemical) paths. In this case a
      peaked conical intersection is located between the two paths. Finally, a third
      type of energy surface is documented for the bismethyleneadamantane radical
      cation and occurs when there is, effectively, a seam of intersection points (not
      a conical intersection) which separates the reactant and product regions. Since
      the reaction path cannot avoid the intersection, IET can only occur
      nonadiabatically. These IET paths indicate that quite different IET mechanisms
      may operate in radical cations, revealing an unexpectedly enriched and flexible
      mechanistic spectrum. We show that the origin of each path can be analyzed and
      understood in terms of the one-dimensional Marcus-Hush model.

PMID- 11456588
TI  - Spontaneous formation of a diamond-crown structure of Re(8) polyselenide and a
      cage structure of Re(3) polytelluride.

PMID- 11456587
TI  - Chromatographic purification of soluble single-walled carbon nanotubes (s-SWNTS).

PMID- 11456589
TI  - Enthalpy/entropy compensation as a competition between dynamics and bonding: the
      relevance to melting of crystals and biological aggregates.

PMID- 11456590
TI  - Evidence for associative methane loss following protonation of
      (diimine)Pt(II)(Ch(3))(2): three-coordinate 14-electron cations l(2)Pt(Ch(3))(+)
      are not necessarily intermediates in C-H activation at cationic Pt complexes.

PMID- 11456591
TI  - Hydrothermal processing of high-quality multiwall nanotubes from amorphous
      carbon.

PMID- 11456592
TI  - A Helical metal-metal bonded chain via the Pt-->Ag dative bond.

PMID- 11456593
TI  - "Double activation" of constrained geometry and ansa-metallocene group 4 metal
      dialkyls: synthesis, structure, and olefin polymerization study of mono- and
      dicationic aluminate complexes.

PMID- 11456594
TI  - Soybean lipoxygenase-mediated oxygenation of monounsaturated fatty acids to
      enones.

PMID- 11456596
TI  - The C-C bond activation and skeletal rearrangement of cycloalkanone imine by
      Rh(I) catalysts.

PMID- 11456595
TI  - New insights into the mechanism of ruthenium-catalyzed olefin metathesis
      reactions.

PMID- 11456597
TI  - Multiphoton gated photochromic reaction in a diarylethene derivative.

PMID- 11456598
TI  - Modular peptide-based phosphine ligands in asymmetric catalysis: efficient and
      enantioselective Cu-catalyzed conjugate additions to five-, six-, and seven
      membered cyclic enones.

PMID- 11456599
TI  - Presence of the heme-oxo intermediate in oxygenation of carbon monoxide by
      cytochrome c oxidase revealed by resonance Raman spectroscopy.

PMID- 11456600
TI  - Facile allylative dearomatization catalyzed by palladium.

PMID- 11456601
TI  - Unusual diboration of allenes catalyzed by palladium complexes and organic
      iodides: a new efficient route to biboronic compounds.

PMID- 11456602
TI  - Metal sphere photonic crystals by nanomolding.

PMID- 11456603
TI  - Total synthesis of (+)-amphidinolide K.

PMID- 11456604
TI  - Real-Time grazing incidence X-ray diffraction studies of polymerizing N
      octadecyltrimethoxysilane Langmuir monolayers at the air/water interface.

PMID- 11456605
TI  - Effect of laser fluence on laser desorption mass spectra of organothiol self
      assembled monolayers on gold.

PMID- 11456606
TI  - A self-assembly approach to the formation of asymmetric dimers from monodispersed
      spherical colloids.

PMID- 11456607
TI  - Fine-tuning the ring-size of metallacyclophanes: a rational approach to molecular
      pentagons.

PMID- 11456608
TI  - Medium-dependent self-assembly of an amphiphilic peptide: direct observation of
      peptide phase domains at the air-water interface.

PMID- 11456609
TI  - Conformational stability of collagen relies on a stereoelectronic effect.

PMID- 11456610
TI  - Calix[4]arenes comprised of aniline units.

PMID- 11456611
TI  - 2-Benzamidoethyl group--a novel type of phosphate protecting group for
      oligonucleotide synthesis.
AB  - A number of 5'-O-(4,4'-dimethoxytrityl)thymidine N,N-diisopropylamino
      phosphoramidites protected at P(III) with derivatives of 2-benzamidoethanol were
      synthesized and incorporated into synthetic oligonucleotides. Depending on
      substitution patterns at the alkyl chain, amido group, and phenyl ring, the time
      required for removal of these protecting groups using concentrated ammonium
      hydroxide varied from 48 h at 55 degrees C to 25 min at 25 degrees C. Of the 11
      groups studied, 2-[N-isopropyl-N- (4-methoxybenzoyl)amino]ethyl- (H) and omega
      (thionobenzoylamino)alkyl protections (I and K) were most easily removed.
      Derivatives of the 2-[N-methyl-N-benzoylamino]ethyl group (E-G) demonstrated
      moderate stability, but those of the 2-(N-benzoylamino)ethyl group (A-C) were the
      most stable. For the most reactive group, H, a phosphitylating reagent,
      bisamidite 60, was synthesized and used in the preparation of four
      deoxynucleoside phosphoramidites 28 and 65-67, plus the 2'-O-(2-methoxyethyl)-5
      methyluridine phosphoramidite 68. All of these novel building blocks were
      successfully tested in the preparation of natural, 20-mer oligonucleotides and
      their phosphorothioate analogues. With the model phosphotriester 37, the
      mechanism of deprotection was studied and revealed, in the case of group H, a pH
      independent formation of the 2-oxazolinium cation 47. Under aqueous conditions,
      47 gave 54, which in turn was converted in the presence of ammonia to a number of
      identified products. It is important to note that none of the products formed was
      reactive toward the oligonucleotide backbone or nucleic bases. Thus, a general
      strategy for protection of internucleosidic phosphodiester groups is described,
      which may also find application in synthetic organic chemistry of phosphorus(III)
      and (V).

PMID- 11456612
TI  - Mechanistic imperatives for aldose-ketose isomerization in water: specific,
      general base- and metal ion-catalyzed isomerization of glyceraldehyde with proton
      and hydride transfer.
AB  - The deuterium enrichment of dihydroxyacetone obtained from the aldose-ketose
      isomerization of D,L-glyceraldehyde in D(2)O at 25 degrees C was determined by
      (1)H NMR spectroscopy from the integrated areas of the signals for the alpha
      CH(2) and alpha-CHD groups of the product. One mole equivalent of deuterium is
      incorporated into the product when the isomerization is carried out in 150 mM
      pyrophosphate buffer at pD 8.4, but only 0.6 mol equiv of deuterium is
      incorporated into the product of isomerization in the presence of 0.01 M
      deuterioxide ion, so that 40% of the latter isomerization reaction proceeds by
      the intramolecular transfer of hydride ion. Several pathways were identified for
      catalysis of the isomerization of glyceraldehyde to give dihydroxyacetone. The
      isomerization with hydride transfer is strongly catalyzed by added Zn(2+).
      Deprotonation of glyceraldehyde is rate-determining for isomerization with proton
      transfer, and this proton-transfer reaction is catalyzed by Bronsted bases.
      Proton transfer also occurs by a termolecular pathway with catalysis by the
      combined action of Bronsted bases and Zn(2+). These results show that there is no
      large advantage to the spontaneous isomerization of glyceraldehyde in alkaline
      solution with either proton or hydride transfer, and that effective catalytic
      pathways exist to stabilize the transition states for both of these reactions in
      water. The existence of separate enzymes that catalyze the isomerization of
      sugars with hydride transfer and the isomerization of sugar phosphates with
      proton transfer is proposed to be a consequence of the lack of any large
      advantage to reaction by either of these pathways for the corresponding
      nonenzymatic isomerization in water.

PMID- 11456613
TI  - Free-probe fluorescence of light-up probes.
AB  - The fluorescence enhancement of light-up probes (thiazole orange (TO) conjugated
      peptide nucleic acids (PNAs)) upon hybridization to target nucleic acid depends
      on the probe sequence, mainly due to large variations in free-probe fluorescence.
      Here we study three probes where the fluorescence in free state varies more than
      50-fold. We find that this variation is due to a fraction that has TO
      intramolecularly "back-bound" to the PNA bases. The intramolecular affinity
      constant for this unimolecular interaction was determined by temperature
      titrations using absorption spectroscopy, and the fluorescence quantum yields of
      the probes in back-bound conformation were calculated. The molar ratio of probes
      in back-bound conformation was 0.70-0.96 at 30 degrees C and 0.40-0.73 at 60
      degrees C, and the fluorescence quantum yield in back-bound conformation varied
      between 0.0020 and 0.077 at 30 degrees C, and 0.00065-0.029 at 60 degrees C.
      These data show that the variation in free-probe fluorescence depends mainly on
      the fluorescence quantum yield of the probe in back-bound conformation and to a
      much lesser extent on the tendency of the probe to adopt the back-bound
      conformation. With increasing temperature the free-probe fluorescence decreases
      owing to both reduced degree of back-binding and a decrease of the fluorescence
      quantum yield in back-bound conformation.

PMID- 11456614
TI  - Application of self-organizing maps in conformational analysis of lipids.
AB  - The characteristics of lipid assemblies are important for the functions of
      biological membranes. This has led to an increasing utilization of molecular
      dynamics simulations for the elucidation of the structural features of
      biomembranes. We have applied the self-organizing map (SOM) to the analysis of
      the complex conformational data from a 1-ns molecular dynamics simulation of PLPC
      phospholipids in a membrane assembly. Mapping of 1.44 million molecular
      conformations to a two-dimensional array of neurons revealed, without human
      intervention, the main conformational features in hours. Both the whole molecule
      and the characteristics of the unsaturated fatty acid chains were analyzed. All
      major structural features were easily distinguished, such as the orientational
      variability of the headgroup, the mainly trans state dihedral angles of the sn-1
      chain, and both straight and bent conformations of the unsaturated sn-2 chain.
      Furthermore, presentation of the trajectory of an individual lipid molecule on
      the map provides information on conformational dynamics. The present results
      suggest that the SOM method provides a powerful tool for routinely gaining rapid
      insight to the main molecular conformations as well as to the conformational
      dynamics of any simulated molecular assembly without the requirement of a priori
      knowledge.

PMID- 11456615
TI  - Mobility of the active site bound paraoxon and sarin in zinc-phosphotriesterase
      by molecular dynamics simulation and quantum chemical calculation.
AB  - The kinetic data published on phosphotriesterase (PTE), with various complexed
      metals, clearly indicates that the P=O and P=S bonds of phosphotriester and
      thiophosphotriester substrates, respectively, are strongly polarized by one or
      both of the active site complexed metal ions. However, this observation is not
      consistent with the three-dimensional X-ray crystal structure of zinc-substituted
      PTE with active site bound substrate analogue diethyl 4-methylbenzylphosphonate.
      In this structure, the distance between the phosphoryl oxygen and the nearest
      zinc is 3.4 A, a distance too large to afford strong polarization. In the present
      paper, the geometry and mobility of various PTE active site-substrate complexes
      are examined by performing both molecular dynamics (MD) simulations and quantum
      mechanical calculations. Two known substrates are considered, paraoxon and sarin,
      although their turnover rates vary about 100-fold. The results indicate that PTE
      forms a complex with either substrate in which the phosphoryl oxygen becomes
      strongly coordinated with the less buried zinc atom. It is shown that the
      geometry of the active site is changed when the protein is immersed in a water
      bath and relaxed by MD. The most substantial conformational change is the opening
      of the gateway in a pocket where the location of the leaving group is expected.
      The opening is observed for the pure enzyme as well as for the enzyme/substrate
      complexes and it ranges from 11 to 18 A. It is also shown that the pockets, in
      which the substrate substituents are localized, exhibit different flexibility and
      interact with the substrate with coordinated conformational adjustments.

PMID- 11456616
TI  - Crystal structures of the soluble methane monooxygenase hydroxylase from
      Methylococcus capsulatus (Bath) demonstrating geometrical variability at the
      dinuclear iron active site.
AB  - The oxidation of methane to methanol is performed at carboxylate-bridged
      dinuclear iron centers in the soluble methane monooxygenase hydroxylase (MMOH).
      Previous structural studies of MMOH, and the related R2 subunit of ribonucleotide
      reductase, have demonstrated the occurrence of carboxylate shifts involving
      glutamate residues that ligate the catalytic iron atoms. These shifts are thought
      to have important mechanistic implications. Recent kinetic and theoretical
      studies have also emphasized the importance of hydrogen bonding and pH effects at
      the active site. We report here crystal structures of MMOH from Methylococcus
      capsulatus (Bath) in the diiron(II), diiron(III), and mixed-valent Fe(II)Fe(III)
      oxidation states, and at pH values of 6.2, 7.0, and 8.5. These structures were
      investigated in an effort to delineate the range of possible motions at the MMOH
      active site and to identify hydrogen-bonding interactions that may be important
      in understanding catalysis by the enzyme. Our results present the first view of
      the diiron center in the mixed-valent state, and they indicate an increased
      lability for ferrous ions in the enzyme. Alternate conformations of Asn214 near
      the active site according to redox state and a distortion in one of the alpha
      helices adjacent to the metal center in the diiron(II) state have also been
      identified. These changes alter the surface of the protein in the vicinity of the
      catalytic core and may have implications for small-molecule accessibility to the
      active site and for protein component interactions in the methane monooxygenase
      system. Collectively, these results help to explain previous spectroscopic
      observations and provide new insight into catalysis by the enzyme.

PMID- 11456617
TI  - Glutathione peroxidase-like antioxidant activity of diaryl diselenides: a
      mechanistic study.
AB  - The synthesis, structure, and thiol peroxidase-like antioxidant activities of
      several diaryl diselenides having intramolecularly coordinating amino groups are
      described. The diselenides derived from enantiomerically pure R-(+)- and S-(-)
      N,N-dimethyl(1-ferrocenylethyl)amine show excellent peroxidase activity. To
      investigate the mechanistic role of various organoselenium intermediates, a
      detailed in situ characterization of the intermediates has been carried out by
      (77)Se NMR spectroscopy. While most of the diselenides exert their peroxidase
      activity via selenol, selenenic acid, and selenenyl sulfide intermediates, the
      differences in the relative activities of the diselenides are due to the varying
      degree of intramolecular Se.N interaction. The diselenides having strong Se.N
      interactions are found to be inactive due to the ability of their selenenyl
      sulfide derivatives to enhance the reverse GPx cycle (RSeSR + H(2)O(2) = RSeOH).
      In these cases, the nucleophilic attack of thiol takes place preferentially at
      selenium rather than sulfur and this reduces the formation of selenol by
      terminating the forward reaction. On the other hand, the diselenides having weak
      Se.N interactions are found to be more active due to the fast reaction of the
      selenenyl sulfide derivatives with thiol to produce diphenyl disulfide and the
      expected selenol (RSeSR + PhSH = PhSSPh + RSeH). The unsubstituted diaryl
      diselenides are found to be less active due to the slow reactions of these
      diselenides with thiol and hydrogen peroxide and also due to the instability of
      the intermediates. The catalytic cycles of 18 and 19 strongly resemble the
      mechanism by which the natural enzyme, glutathione peroxidase, catalyzes the
      reduction of hydroperoxides.

PMID- 11456618
TI  - Pd-catalyzed inter- and intramolecular carbene transfer from group 6 metal
      carbene complexes.
AB  - The use of group 6 metal-carbene complexes in inter- and intramolecular carbene
      transfer reactions has been studied. Thus,
      pentacarbonyl[(aryl)(methoxy)carbene]chromium(0) and tungsten complexes, 10,
      efficiently dimerize at room temperature in the presence of diverse Pd(0) and
      Pd(II)/Et(3)N catalysts. The effect of additives (PPh(3), AsPh(3), or SbPh(3)) on
      the nature and the isomeric ratio of the reaction products is negligible. The
      nature of the reaction products is more catalyst-dependent for metal carbenes 12
      bearing alkyl groups attached to the carbene carbon. In these cases, either
      carbene ligand dimerization or beta-hydrogen elimination reactions are observed,
      depending on the catalyst. The carbene ligand dimerization reaction can be used
      to prepare conjugated polyenes, including those having metal moieties at both
      ends of the polyene system, as well as enediyne derivatives. The intramolecular
      carbene ligand dimerization of chromium bis-carbene complexes 28 and 30 allows
      the preparation of mono- and bicyclic derivatives, with ring sizes from six to
      nine members. For bis-carbene derivatives the beta-hydrogen elimination reaction
      is inhibited, provided that both metal centers are tethered by an o-xylylene
      group. Other alkyl complexes 32 form new mononuclear carbene complexes 37 or
      decompose to complex reaction mixtures. The results obtained in these reactions
      may be explained by transmetalation from Cr(0) to Pd(0) and the intermediacy of
      Pd-carbene complexes. Aminocarbene-chromium(0) complexes 15, need harsher
      reaction conditions to transfer the carbene ligand, and this transfer occurs only
      in the presence of deactivated olefins. The corresponding insertion/hydrolysis
      products 48 resulted in these cases. A catalytic cycle involving transmetalation
      from a chromacyclobutane to a palladacyclobutane is proposed to explain these
      results.

PMID- 11456619
TI  - New molybdenum catalysts for alkyl olefin epoxidation. Their implications for the
      mechanism of oxygen atom transfer.
AB  - We report here the design, synthesis, and characterization of new (dioxo)Mo(VI)
      epoxidation catalysts based on monoanionic tridentate ligands. Two important
      features distinguish these catalysts from those previously reported. First, their
      coordination environment remains well-defined during the epoxidation reaction.
      Second, the ligand design does not permit simultaneous coordination of olefin and
      alkyl hydroperoxide. Based on the study of these new catalysts, we conclude that
      direct oxygen atom transfer from coordinated alkyl peroxide to olefin remains the
      simplest mechanism consistent with the available data. We discuss literature
      discrepancies in this regard.

PMID- 11456620
TI  - Stereochemical elucidation and total synthesis of dihydropacidamycin D, a
      semisynthetic pacidamycin.
AB  - Hydrogenation of the C(4') exocyclic olefin of the pacidamycins has been shown to
      produce a series of semisynthetic compounds, the dihydropacidamycins, with
      antimicrobial activity similar to that of the natural products. Elucidation of
      stereochemistry in the pacidamycins has been completed through a campaign of
      natural product degradation experiments in combination with the total synthesis
      of the lowest-molecular weight dihydropacidamycin, dihydropacidamycin D. The
      stereochemical identities of the tryptophan and two alanine residues contained in
      pacidamycin D have been shown to be of the natural (S) configuration, and the
      unique 3-methylamino-2-aminobutyric acid contained in this series of antibiotics
      has been shown to be of the (2S,3S) configuration. Finally, the stereochemistry
      obtained by hydrogenation of the C(4')-C(5') exocyclic olefin has been shown to
      be (R) at the C(4') nucleoside site.

PMID- 11456621
TI  - Gemini surfactants with a disaccharide spacer.
AB  - A gemini surfactant is an amphiphile possessing (in sequence) the following:
      hydrocarbon tail/polar group/spacer/polar group/hydrocarbon tail. Widespread
      interest in geminis has emerged recently from both industrial and academic
      laboratories. In the present contribution, two related families of geminis have
      been synthesized, both with trehalose, a disaccharide, as a polar spacer. One
      family, Series-A, is nonionic and has amide groups separating the long chains
      from the trehalose spacer. The other family, Series-B, has quaternary ammonium
      ions connecting the long chains to the trehalose spacer. It was found that Series
      A geminis are water insoluble despite the two amides and multiple hydroxyls. When
      hydrated or extruded, these geminis form microscopically visible vesicular and
      tubular structures above their transition temperatures (which were determined
      calorimetrically). Insoluble monomolecular films, constructed from these geminis,
      have interfacial areas that are dominated by the sugar spacer although
      intermolecular chain/chain interactions seem to stabilize the films. Thus, the
      behavior of Series-A geminis in many ways parallels that of phospholipids and
      simple double-chain surfactants. It is as if the trehalose is less of a spacer
      than a large but conventional headgroup. In contrast, cationic Series-B geminis
      are water soluble and form micelles with critical micelle concentrations an order
      of magnitude lower than that of corresponding conventional surfactants. Molecular
      modeling using the Amber force field explains the difference in properties
      between the two families of geminis. Series-A are tubular in shape and thus
      prefer bilayer packing as do other amphiphiles in which the headgroups are
      similar in width to the sum of the tail diameters. Series-B geminis are conical
      shaped and pack more readily into spherical micelles. This work entails
      synthesis, tensiometry, conductance, microscopy, surface balance studies,
      calorimetry, light scattering, and molecular modeling. In colloid chemistry, a
      balanced perspective cannot be achieved by one methodology alone but only through
      the pursuit of consilience among multiple approaches.

PMID- 11456622
TI  - Polyoxometalate HIV-1 protease inhibitors. A new mode of protease inhibition.
AB  - Nb-containing polyoxometalates (POMs) of the Wells-Dawson class inhibit HIV-1
      protease (HIV-1P) by a new mode based on kinetics, binding, and molecular
      modeling studies. Reaction of alpha(1)-K(9)Li[P(2)W(17)O(61)] or alpha(2)
      K(10)[P(2)W(17)O(61)] with aqueous H(2)O(2) solutions of K(7)H[Nb(6)O(19)]
      followed by treatment with HCl and KCl and then crystallization affords the
      complexes alpha(1)-K(7)[P(2)W(17)(NbO(2))O(61)] (alpha(1)()1) and alpha(2)
      K(7)[P(2)W(17)(NbO(2))O(61)] (alpha(2)()1) in 63 and 86% isolated yields,
      respectively. Thermolysis of the crude peroxoniobium compounds (72-96 h in
      refluxing H(2)O) prior to treatment with KCl converts the peroxoniobium compounds
      to the corresponding polyoxometalates (POMs), alpha(1)-K(7)[P(2)W(17)NbO(62)]
      (alpha(1)()2) and alpha(2)-K(7)[P(2)W(17)NbO(62)] (alpha(2)()2), in moderate
      yields (66 and 52%, respectively). The identity and high purity of all four
      compounds were confirmed by (31)P NMR and (183)W NMR. The acid-induced
      dimerization of the oxo complexes differentiates sterically between the cap
      (alpha(2)) site and the belt (alpha(1)) site in the Wells-Dawson structure
      (alpha(2)()2 dimerizes in high yield; alpha(1)()2 does not). All four POMs
      exhibit high activity in cell culture against HIV-1 (EC(50) values of 0.17-0.83
      microM), are minimally toxic (IC(50) values of 50 to >100 microM), and
      selectively inhibit purified HIV-1 protease (HIV-1P) (IC(50) values for
      alpha(1)()1, alpha(2)()1, alpha(1)()2, and alpha(2)()2 of 2.0, 1.2, 1.5, and 1.8
      microM, respectively). Thus, theoretical, binding, and kinetics studies of the
      POM/HIV-1P interaction(s) were conducted. Parameters for [P(2)W(17)NbO(62)](7)(-)
      were determined for the Kollman all-atom (KAA) force field in Sybyl 6.2. Charges
      for the POM were obtained from natural population analysis (NPA) at the
      HF/LANL2DZ level of theory. AutoDock 2.2 was used to explore possible binding
      locations for the POM with HIV-1P. These computational studies strongly suggest
      that the POMs function not by binding to the active site of HIV-1P, the mode of
      inhibition of all other HIV-1P protease inhibitors, but by binding to a cationic
      pocket on the "hinge" region of the flaps covering the active site (2 POMs and
      cationic pockets per active homodimer of HIV-1P). The kinetics and binding
      studies, conducted after the molecular modeling, are both in remarkable agreement
      with the modeling results: 2 POMs bind per HIV-1P homodimer with high affinities
      (K(i) = 1.1 +/- 0.5 and 4.1 +/- 1.8 nM in 0.1 and 1.0 M NaCl, respectively) and
      inhibition is noncompetitive (k(cat) but not K(m) is affected by the POM
      concentration).

PMID- 11456623
TI  - Solution structures and dynamic properties of chelated d(0) metal olefin
      complexes [eta(5): eta(1)-C(5)R(4)SiMe(2)N(t)Bu]Ti(OCMe(2)CH(2)CH(2)CH=CH(2))(+)
      (R = H, Me): Models for the [eta(5): eta(1)
      C(5)R(4)SiMe(2)N(t)Bu]Ti(R')(olefin)(+) intermediates in "constrained geometry"
      catalysts.
AB  - To model the Ti-olefin interaction in the putative [eta(5): eta(1)
      C(5)R(4)SiMe(2)N(t)Bu]Ti(R')(olefin)(+) intermediates in "constrained geometry"
      Ti-catalyzed olefin polymerization, chelated alkoxide olefin complexes [eta(5):
      eta(1)-C(5)R(4)SiMe(2)N(t)Bu]Ti(OCMe(2)CH(2)CH(2)CH=CH(2))(+) have been
      investigated. The reaction of [eta(5): eta(1)-C(5)R(4)SiMe(2)N(t)Bu]TiMe(2)
      (1a,b; R = H, Me) with HOCMe(2)CH(2)CH(2)CH=CH(2) yields mixtures of [eta(5)
      C(5)R(4)SiMe(2)NH(t)Bu]TiMe(2)(OCMe(2)CH(2)CH(2)CH=CH(2)) (2a,b) and [eta(5):
      eta(1)-C(5)R(4)SiMe(2)N(t)Bu]TiMe(OCMe(2)CH(2)CH(2)CH=CH(2)) (3a,b). The reaction
      of 2a/3a and 2b/3b mixtures with B(C(6)F(5))(3) yields the chelated olefin
      complexes [[eta(5): eta(1)
      C(5)R(4)SiMe(2)N(t)Bu]Ti(OCMe(2)CH(2)CH(2)CH=CH(2))][MeB(C(6)F(5))(3)] (4a,b; 71
      and 89% NMR yield). The reaction of 2b/3b with [Ph(3)C][B(C(6)F(5))(4)] yields
      [[eta(5): eta(1)
      C(5)Me(4)SiMe(2)N(t)Bu]Ti(OCMe(2)CH(2)CH(2)CH=CH(2))][B(C(6)F(5))(4)] (5b, 88%
      NMR yield). NMR studies establish that 4a,b and 5b exist as mixtures of
      diastereomers (isomer ratios: 4a/4a', 62/38; 4b/4b', 75/25; 5b/5b', 75/25), which
      differ in the enantioface of the olefin that is coordinated. NMR data for these
      d(0) metal olefin complexes show that the olefin coordinates to Ti in an
      unsymmetrical fashion primarily through C(term) such that the C=C pi bond is
      polarized with positive charge buildup on C(int). Dynamic NMR studies show that
      4b/4b' undergoes olefin face exchange by a dissociative mechanism which is
      accompanied by fast inversion of configuration at Ti ("O-shift") in the olefin
      dissociated intermediate. The activation parameters for the conversion of 4b to
      4b' (i.e., 4b/4b' face exchange) are: DeltaH = 17.2(8) kcal/mol; DeltaS = 8(1)
      eu. 4a/4a' also undergoes olefin face exchange but with a lower barrier (DeltaH =
      12.2(9) kcal/mol; DeltaS = -2(3) eu), for the conversion of 4a to 4a'.

PMID- 11456624
TI  - Manipulation of the director in bicellar mesophases by sample spinning: a new
      tool for NMR spectroscopy.
AB  - It is shown that bicellar nematic liquid-crystalline phases can be oriented with
      the director (the normal to the bicellar plane) at an arbitrary angle to the
      applied magnetic field by sample rotation around one axis (variable-angle sample
      spinning) or around two axes successively (switched-angle spinning). This
      promises to open novel possibilities for NMR studies of bicelles and proteins
      incorporated into bicelles or dissolved in a solution containing bicelles,
      including the correlation of several orientations in a two-dimensional NMR
      experiment.

PMID- 11456625
TI  - Orientation of amide-nitrogen-15 chemical shift tensors in peptides: a quantum
      chemical study.
AB  - Knowledge of the orientation of the nitrogen-15 chemical shift anisotropy (CSA)
      tensor is critical for a variety of experiments that provide information on
      protein structure and dynamics in the solid and solution states. Unfortunately,
      the methods available for determining the orientation of the CSA tensor
      experimentally have inherent limitations. Rotation studies of a single crystal
      provide complete information but are tedious and limited in applicability. Solid
      state NMR studies on powder samples can be applied to a greater range of samples
      but suffer from ambiguities in the results obtained. Density functional gauge
      including-atomic-orbitals (GIAO) calculations of the orientations of (15)N CSA
      tensors in peptides are presented here as an independent source of confirmation
      for these studies. A comparison of the calculated (15)N CSA orientations with the
      available experimental values from single-crystal and powder studies shows
      excellent agreement after a partial, constrained optimization of some of the
      crystal structures used in the calculation. The results from this study suggest
      that the orientation as well as the magnitudes of (15)N CSA tensors may vary from
      molecule to molecule. The calculated alpha(N) angle varies from 0 degrees to 24
      degrees with the majority in the 10 degrees to 20 degrees range and the beta(N)
      angle varies from 17 degrees to 24 degrees in good agreement with most of the
      solid-state NMR experimental results. Hydrogen bonding is shown to have
      negligible effect on the orientation of (15)N CSA tensor in accordance with
      recent theoretical predictions. Furthermore, it is demonstrated that the
      orientation of the (15)N CSA can be calculated accurately with much smaller basis
      sets than is needed to calculate the chemical shift, suggesting that the routine
      application of ab initio calculations to the determination of (15)N CSA tensor
      orientations in large biomolecules might be possible.

PMID- 11456626
TI  - Influence of hydroxyl substitution on benzyne properties. quantum chemical
      characterization of the didehydrophenols.
AB  - Geometries and singlet-triplet splittings for the 10 geometrical isomers of
      didehydrophenol are characterized at a variety of levels of electronic structure
      theory. The influence of the hydroxyl group is primarily to increase/decrease the
      weight of zwitterionic singlet mesomers that place positive/negative charge
      adjacent to oxygen in valence bond descriptions of the arynes. For some of the
      meta isomers, this interaction stabilizes distortion in the direction of a
      bicyclic geometry. The net effect, relative to the unsubstituted benzynes, is to
      increase the singlet-triplet splittings in 2,3-, 2,6-, and 3,5-didehydrophenol
      and to decrease that splitting in 2,4- and 2,5-didehydrophenol (3,4
      didehydrophenol is essentially unaffected). As shown for other arynes, the
      singlet-triplet splittings can also be accurately estimated by correlation with
      proton hyperfine coupling constants in antecedent monoradicals, these values
      being accessible from very economical calculations.

PMID- 11456627
TI  - Trapping-mediated dissociative chemisorption of cycloalkanes on Ru(001) and
      Ir(111): influence of ring strain and molecular geometry on the activation of C-C
      and C-H bonds.
AB  - We have measured the initial probabilities of dissociative chemisorption of
      perhydrido and perdeutero cycloalkane isotopomers on the hexagonally close-packed
      Ru(001) and Ir(111) single-crystalline surfaces for surface temperatures between
      250 and 1100 K. Kinetic parameters (activation barrier and preexponential factor)
      describing the initial, rate-limiting C-H or C-C bond cleavage reactions were
      quantified for each cycloalkane isotopomer on each surface. Determination of the
      dominant initial reaction mechanism as either initial C-C or C-H bond cleavage
      was judged by the presence or absence of a kinetic isotope effect between the
      activation barriers for each cycloalkane isotopomer pair, and also by comparison
      with other relevant alkane activation barriers. On the Ir(111) surface, the
      dissociative chemisorption of cyclobutane, cyclopentane, and cyclohexane occurs
      via two different reaction pathways: initial C-C bond cleavage dominates on
      Ir(111) at high temperature (T > approximately 600 K), while at low temperature
      (T < approximately 400 K), initial C-H bond cleavage dominates. On the Ru(001)
      surface, dissociative chemisorption of cyclopentane occurs via initial C-C bond
      cleavage over the entire temperature range studied, whereas dissociative
      chemisorption of both cyclohexane and cyclooctane occurs via initial C-H bond
      cleavage. Comparison of the cycloalkane C-C bond activation barriers measured
      here with those reported previously in the literature qualitatively suggests that
      the difference in ring-strain energies between the initial state and the
      transition state for ring-opening C-C bond cleavage effectively lowers or raises
      the activation barrier for dissociative chemisorption via C-C bond cleavage,
      depending on whether the transition state is less or more strained than the
      initial state. Moreover, steric arguments and metal-carbon bond strength
      arguments have been evoked to explain the observed trend of decreasing C-H bond
      activation barrier with decreasing cycloalkane ring size.

PMID- 11456628
TI  - Probing aerogels by multiple quantum filtered (131)Xe NMR spectroscopy.
AB  - At the interface between solid surfaces and cavities filled with gaseous or
      liquid xenon, the nuclear magnetization of (131)Xe (S = (3)/(2)) is subject to
      quadrupolar interactions which may lead to higher rank single-quantum coherences
      that can be described by tensor elements T(2,)(+/-)(1) and T(3,)(+/-)(1). This
      can be demonstrated by multiple-quantum filtered (MQF) NMR experiments. In
      gaseous xenon on Pyrex surfaces, the primary source of such coherences was shown
      to be coherent evolution induced by a nonvanishing average quadrupolar coupling.
      In this contribution, MQF NMR is applied to aerogels filled with liquid xenon to
      demonstrate the potential of this technique for material sciences. Xenon in the
      liquid phase provides a sufficient spin density to obtain reasonable signal-to
      noise ratios. Coherent evolution and relaxation both contribute to the creation
      of higher rank coherences depending on the presence or absence of water molecules
      on the surface. These two processes can be distinguished experimentally and
      provide complementary information about the surface of the host material.

PMID- 11456629
TI  - Polyfluorenes with polyphenylene dendron side chains: toward non-aggregating,
      light-emitting polymers.
AB  - A polyfluorene 12 has been prepared in which bulky polyphenylene dendrimer
      substituents suppress formation of long wavelength emitting aggregates, thus
      giving a polymer with pure blue emission. Absorption- and emission spectra and
      molecular modeling confirm that the bulky dendrimer side chains do not cause
      extra torsion between the fluorene units. New polyfluorenes with 9,9-diaryl
      substituents have been prepared to determine the minimum size of substituent
      necessary for aggregation suppression. An LED using 12 has been demonstrated to
      produce blue emission with onset voltages below 4 V.

PMID- 11456630
TI  - Polarity of layer-by-layer deposited polyelectrolyte films as determined by
      pyrene fluorescence.
AB  - The polarity of polyelectrolyte (PE) multilayer films is investigated with pyrene
      as a polarity-sensitive probe. Multilayer films of poly(styrene sulfonate) (PSS)
      and various polycations were prepared by the layer-by-layer self-assembly
      technique. Pyrene (PY) molecules were inserted into the films by exposing the
      multilayers to pyrene solutions. By this method a homogeneous distribution of
      pyrene molecules at low concentration within the film was obtained. The ratio of
      the fluorescence intensities of the first (I) to the third (III) vibronic band
      (Py-value) of the pyrene emission spectrum is employed here to determine the
      polarity of the PE films. PSS and poly(allylamine hydrochloride) (PAH) multilayer
      films yielded a pyrene value close to the solvent polarity of acetone, while
      multilayers of PSS and poly(diallyldimethylammonium chloride) (PDADMAC) displayed
      a value higher than the one corresponding to water. The pyrene values of the
      polyelectrolyte films were independent from the solvent employed for probe
      dissolving. Although no direct relationship between solvent polarity and
      dielectric constant (epsilon) is available, an estimate of the static dielectric
      constant of the films can be provided by comparing the Py-values of the films
      with those of various solvents. Changes in the humidity conditions of the film
      environment in a closed cell did not affect the film polarity. However, a drastic
      and irreversible reduction of polarity could be induced by actively drying the
      samples by a nitrogen flow.

PMID- 11456631
TI  - Electronic spectroscopy and photoisomerization of trans-urocanic acid in a
      supersonic jet.
AB  - trans-Urocanic acid (trans-UA), a component of the epidermal layer of skin,
      exhibits wavelength-dependent photochemistry. The quantum efficiency of
      isomerization to cis-UA is greatest when the molecule is excited on the long
      wavelength tail of its absorption profile in solution (300-320 nm). However,
      exciting the molecule where it absorbs UV light most efficiently (260-285 nm)
      causes almost no isomerization. We have used fluorescence excitation and
      dispersed emission methods in a supersonic jet to investigate the electronic
      states involved in this complex and interesting photochemistry. Three distinct
      regions are present in the excitation spectrum. Region I, which is below the
      isomerization barrier, contains sharp, well-resolved peaks that upon excitation
      emit from the S(1) state of trans-UA. Region II exhibits peaks that increase in
      broadness and decrease in intensity with increasing excitation energy. Upon
      excitation these peaks produce dual emission from the S(1) states of both trans-
      and cis-UA. The trans to cis isomerization barrier is estimated to be 1400 cm(
      1). Region III exhibits excitation to the S(2) electronic state and has a broad
      structure that spans 3000 cm(-1) and occurs 4000 cm(-1) above S(1). S(2)
      excitation results in essentially no trans to cis isomerization.

PMID- 11456632
TI  - Measurement of slow (micros-ms) time scale dynamics in protein side chains by
      (15)N relaxation dispersion NMR spectroscopy: application to Asn and Gln residues
      in a cavity mutant of T4 lysozyme.
AB  - A new NMR experiment is presented for the measurement of micros-ms time scale
      dynamics of Asn and Gln side chains in proteins. Exchange contributions to the
      (15)N line widths of side chain residues are determined via a relaxation
      dispersion experiment in which the effective nitrogen transverse relaxation rate
      is measured as a function of the number of refocusing pulses in constant-time,
      variable spacing CPMG intervals. The evolution of magnetization from scalar
      couplings and dipole-dipole cross-correlations, which has limited studies of
      exchange in multi-spin systems in the past, does not affect the extraction of
      accurate exchange parameters from relaxation profiles of NH(2) groups obtained in
      the present experiment. The utility of the method is demonstrated with an
      application to a Leu --> Ala cavity mutant of T4 lysozyme, L99A. It is shown that
      many of the side chain amide groups of Asn and Gln residues in the C-terminal
      domain of the protein are affected by a chemical exchange process which may be
      important in facilitating the rapid binding of hydrophobic ligands to the cavity.

PMID- 11456633
TI  - Mechanism-based inhibition of an essential bacterial adenine DNA
      methyltransferase: rationally designed antibiotics.

PMID- 11456634
TI  - Chemical shielding tensors for a silicon-carbon double bond.

PMID- 11456635
TI  - Dynamic assembly of coordination boxes from (en)Pd(II) unit and a rectangular
      panel-like ligand: NMR, CSI-MS, and X-ray studies.

PMID- 11456636
TI  - Intermolecular C-H insertions and cyclization reactions involving a stable
      germylene.

PMID- 11456637
TI  - Enantioselective synthesis of arylamines through Zr-catalyzed addition of
      dialkylzincs to imines. Reaction development by screening of parallel libraries.

PMID- 11456638
TI  - Highly efficient and thermally stable nonlinear optical dendrimer for
      electrooptics.

PMID- 11456639
TI  - Micellization of hydrocarbon surfactants in supercritical carbon dioxide.

PMID- 11456640
TI  - On the reversible nature of the olefin cross metathesis reaction.

PMID- 11456642
TI  - A new strategy to achieve perfectly planar carbon tetracoordination.

PMID- 11456641
TI  - 67Zn solid-state NMR spectroscopy of the minimal dna binding domain of human
      nucleotide excision repair protein XPA.

PMID- 11456643
TI  - Stereochemistry of the thermal retro-Diels-Alder reactions of cis,exo-5,6-d(2)
      bicyclo[2.2.1]hept-2-ene, cis-4,5-d2-cyclohexene, and cis,exo-5,6-d2
      bicyclo[2.2.2]oct-2-ene.

PMID- 11456644
TI  - A new structural motif for the design of potent glucosidase inhibitors.

PMID- 11456645
TI  - Catalytic Shilov chemistry: platinum chloride-catalyzed oxidation of terminal
      methyl groups by dioxygen.

PMID- 11456646
TI  - Discovery and characterization of a discretely folded homotrimeric betabetaalpha
      peptide.

PMID- 11456647
TI  - Highly diastereoselective and enantioselective carbon-carbon bond formations in
      conjugate additions of lithiated N-Boc allylamines to nitroalkenes:
      enantioselective synthesis of 3,4- and 3,4,5-substituted piperidines including (
      )-paroxetine.

PMID- 11456648
TI  - Simulation of an S(N)1 reaction in supercritical water.

PMID- 11456649
TI  - One-step, chemisorbed immobilization of highly stable, polydiacetylenic
      phospholipid vesicles onto gold films.

PMID- 11456650
TI  - Sensitivity-enhanced NMR of biological solids: dynamic nuclear polarization of
      Y21M fd bacteriophage and purple membrane.

PMID- 11456651
TI  - Thermodynamic stabilization mechanism of block copolymer vesicles.

PMID- 11456652
TI  - Rapid validation of the overall structure of an internal domain-swapped mutant of
      the anti-HIV protein cyanovirin-N using residual dipolar couplings.

PMID- 11456654
TI  - Remarkable synthesis of 2-(Z)-6-(E)-4H-[1,4]-thiazepin-5-ones by zwitteronic
      rhodium-catalyzed chemo- and regioselective cyclohyrocarbonylative ring expansion
      of acetylenic thiazoles.
AB  - Cyclohydrocarbonylative ring expansion of acetylenic thiazoles in the presence of
      CO, H(2), and catalytic quantities of the zwitterionic rhodium complex (eta(6)
      C(6)H(5)BPh(3))(-)Rh(+)(1,5-COD) and triphenyl phosphite affords thiazepinones in
      61 to 90% yields. This novel transformation of a 5- to a 7-membered heterocycle
      is readily applied to acetylenic thiazoles containing hydro, alkyl, alkyl halide,
      vinyl, and benzo substitutents in positions 4 and 5 of the thiazole ring in
      addition to alkyl-, ether-, ester-, vinyl-, and aryl-substituted alkynes at
      position 2.

PMID- 11456655
TI  - Synthesis of functional Ras lipoproteins and fluorescent derivatives.
AB  - For the study of biological signal transduction, access to correctly lipidated
      proteins is of utmost importance. Furthermore, access to bioconjugates that
      embody the correct structure of the protein but that may additionally carry
      different lipid groups or labels (i.e., fluorescent tags) by which the protein
      can be traced in biological systems, could provide invaluable reagents. We report
      here of the development of techniques for the synthesis of a series of modified
      Ras proteins. These modified Ras proteins carry a number of different, natural
      and non-natural lipid residues, and the process was extended to also provide
      access to a number of fluorescently labeled derivatives. The maleimide group
      provided the key to link chemically synthesized lipopeptide molecules in a
      specific and efficient manner to a truncated form of the H-Ras protein.
      Furthermore, a preliminary study on the biological activity of the natural Ras
      protein derivative (containing the normal farnesyl and palmitoyl lipid residues)
      has shown full biological activity. This result highlights the usefulness of
      these compounds as invaluable tools for the study of Ras signal transduction
      processes and the plasma membrane localization of the Ras proteins.

PMID- 11456656
TI  - DFT study of H--H activation by Cp(2) LnH d(0) complexes.
AB  - The energy required to activate the H--H bond in the entire series of Cp(2)LnH
      complexes has been calculated by DFT (B3PW91) methods. The activation energies
      have been calculated to vary from 0.5 to 8.0 kcal x mol(-1), indicating an
      overall facile reaction. The electronegativity of the lanthanide in its most
      stable oxidation state is suggested to be a leading factor for interpreting the
      trends in activation energy. The geometry of the transition state is best viewed
      as an almost linear H(3)(-) ligand with short H--H distances and strong M--H
      interaction, through the wingtip H centers, with Ln. The exchange reaction is
      thus established to be a sigma bond metathesis reaction.

PMID- 11456657
TI  - 2.1 and 1.8 A average C(alpha) RMSD structure predictions on two small proteins,
      HP-36 and s15.
AB  - On two different small proteins, the 36-mer villin headpiece domain (HP-36) and
      the 65-mer structured region of ribosomal protein (S15), several model
      predictions from the ab initio approach Rosetta were subjected to molecular
      dynamics simulations for refinement. After clustering the resulting trajectories
      into conformational families, the average molecular mechanics--Poisson
      Boltzmann/surface area (MM-PBSA) free energies and alpha carbon (C(alpha)) RMSDs
      were then calculated for each family. Those conformational families with the
      lowest average free energies also contained the best C(alpha) RMSD structures
      (1.4 A for S15 and HP-36 core) and the lowest average C(alpha) RMSDs (1.8 A for
      S15, 2.1 A for HP-36 core). For comparison, control simulations starting with the
      two experimental structures were very stable, each consisting of a single
      conformational family, with an average C(alpha) RMSD of 1.3 A for S15 and 1.2 A
      for HP-36 core (1.9 A over all residues). In addition, the average free energies'
      ranks (Spearman rank, r(s)) correlate well with the average C(alpha) RMSDs (r(s)
      = 0.77 for HP-36, r(s) = 0.83 for S15). Molecular dynamics simulations combined
      with the MM--PBSA free energy function provide a potentially powerful tool for
      the protein structure prediction community in allowing for both high-resolution
      structural refinement and accurate ranking of model predictions. With all of the
      information that genomics is now providing, this methodology may allow for
      advances in going from sequence to structure.

PMID- 11456658
TI  - Reactivity of zinc finger cores: analysis of protein packing and electrostatic
      screening.
AB  - The chemical stability of 207 zinc fingers, derived from 92 experimental protein
      structures, is evaluated according to the protein packing and electrostatic
      screening of their zinc cores. These properties are used as measures of the
      protein protection of zinc cores, to predictively rank relative zinc finger
      reactivities and assess differences in function. On average, there is a
      substantial and concomitant increase in the screening of increasingly anionic
      core motifs, suggesting zinc fingers have evolved in a manner that promotes
      shielding of their potentially reactive core thiolates. In contrast, enzymatic
      zinc cores are functionally differentiated by negative electrostatic screening.
      Zinc finger cores are predominantly screened by networks of backbone:core NH-S
      hydrogen bonds that electronically stabilize core thiolates and enhance backbone
      packing. Stabilizing protein:core interactions can be mapped to conserved
      residues, including [Arg,Lys]:core salt-bridges in some protein families. Labile
      zinc fingers are identified by poorly screened cores, possibly indicating redox
      or metallothionein (MT) regulated function. Consistent with experiment, the cores
      of the C-terminal finger of the human immunodeficiency virus type 1 (HIV-1)
      nucleocapsid protein p7 (NCp7) and Escherichia coli Ada protein (Ada) "finger"
      are identified as reactive. The C-terminal zinc fingers of nuclear receptors are
      predicted to be the most labile in this study, particularly the human estrogen
      receptor (hER), which contains a triad of reactive thiolates. We propose that hER
      DNA binding is redox and MT regulated through the C-terminal finger and that weak
      electrophilic agents may inhibit hER-mediated transcription, implicated in breast
      cancer progression.

PMID- 11456659
TI  - C--N bond formation on addition of aryl carbanions to the electrophilic nitrido
      ligand in TpOs(N)Cl(2).
AB  - The osmium(VI) nitrido complex TpOs(N)Cl(2) (1) has been prepared from
      K[Os(N)O(3)] and KTp in aqueous ethanolic HCl. It reacts rapidly with PhMgCl and
      related reagents with transfer of a phenyl group to the nitrido ligand. This
      forms Os(IV) metalla-analido complexes, which are readily protonated to give the
      analido complex TpOs(NHPh)Cl(2) (4). The nitrido-phenyl derivatives TpOs(N)PhCl
      and TpOs(N)Ph(2) react more slowly with PhMgCl and are not competent
      intermediates for the reaction of 1 with PhMgCl. Reactions of 1 with alkyl- and
      arylboranes similarly result in transfer of one organic group to nitrogen,
      leading to isolable borylamido complexes such as TpOs[N(Ph)(BPh(2))]Cl(2) (11).
      This is an unprecedented insertion of a nitrido ligand into a boron--carbon bond.
      Hydrolysis of 11 gives 4. Mechanistic studies suggest that both the Grignard and
      borane reactions proceed by initial weak coordination of Mg or B to the nitrido
      ligand, followed by migration of the carbanion to nitrogen. The hydrocarbyl group
      does not go to osmium and then move to nitrogen--there is no change in the atoms
      bound to the osmium during the reactions. It is suggested that there may be a
      general preference for nucleophiles to add directly to the metal--ligand multiple
      bond rather than binding to the metal first and migrating. Ab initio calculations
      show that the unusual reactivity of 1 results from its accessible LUMO and LUMO +
      1, which are the Os = N pi* orbitals. The bonding in 1 and its reactivity with
      organoboranes are reminiscent of CO.

PMID- 11456660
TI  - Immobilized metal complexes in porous organic hosts: development of a material
      for the selective and reversible binding of nitric oxide.
AB  - Delivery of NO to specific targets is important in fundamental studies and
      therapeutic applications. Various methods have been reported for delivery of NO
      in vivo and in vitro; however, there are few examples of systems that reversibly
      bind NO. Reported herein is the development of a new polymer (P-1[Co(II)]) that
      reversibly binds NO. P-1[Co(II)] has a significantly higher affinity for NO
      compared to O(2), CO(2), and CO. The polymer is synthesized by template
      copolymerization methods and consists of a porous methacrylate network,
      containing immobilized four-coordinate Co(II) sites. Binding of NO causes an
      immediate color change, indicating coordination of NO to the site-isolated Co(II)
      centers. The formation of P-1[Co(NO)] has been confirmed by EPR, electronic
      absorbance, and X-ray absorption spectroscopies. Electronic and X-ray absorbance
      results for P-1[Co(II)] and P-1[Co(NO)] show that the coordination geometry of
      the immobilized cobalt complexes are similar to those of their monomeric
      analogues and that NO binds directly to the cobalt centers. EPR spectra show that
      the binding of NO to P-1[Co(II)] is reversible in the solid state; the axial EPR
      signal associated with the four-coordinate Co(II) sites in P-1[Co(II)] is
      quenched upon NO binding. At room temperature and atmospheric pressure, 40%
      conversion of P-1[Co(NO)] to P-1[Co(II)] is achieved in 14 days; under vacuum at
      120 degrees C this conversion is complete in approximately 1 h. The binding of NO
      to P-1[Co(II)] is also observed when the polymer is suspended in liquids,
      including water.

PMID- 11456661
TI  - Direct observation of nucleus structure and nucleation pathways in apoferritin
      crystallization.
AB  - Using atomic force microscopy (AFM) in situ during the crystallization of the
      protein apoferritin from its solution, we imaged the arrangement of the molecules
      in near-critical clusters, larger or smaller than the crystal nucleus, that are
      representative of the nucleus structure. At supersaturations Delta mu/k(B)T of
      1.1 -- 1.6 -- 2.3, the nuclei contain about 50 -- 20 -- 10 molecules. The
      molecular arrangement within the nuclei is similar to that in the crystal bulk.
      Contrary to the general belief, the observed nuclei are not compact molecular
      clusters, but are planar arrays of several rods of 4--7 molecules set in one or
      two monomolecular layers. Similarly unexpected nuclei structures might be common,
      especially for anisotropic molecules. Hence, the nucleus structure should be
      considered as a variable by advanced theoretical treatments.

PMID- 11456662
TI  - Hydrogen transfer to carbonyls and imines from a hydroxycyclopentadienyl
      ruthenium hydride: evidence for concerted hydride and proton transfer.
AB  - Reaction of ([2,5-Ph(2)-3,4-Tol(2)(eta(5)-C(4)CO)](2)H)Ru(2)(CO)(4)(mu-H) (6)
      with H(2) formed [2,5-Ph(2)-3,4-Tol(2)(eta(5)-C(4)COH)Ru(CO)(2)H] (8), the active
      species in catalytic carbonyl reductions developed by Shvo. Kinetic studies of
      the reduction of PhCHO by 8 in THF at -10 degrees C showed second-order kinetics
      with Delta H(double dagger) = 12.0 kcal mol(-1) and Delta S(double dagger) = -28
      eu. The rate of reduction was not accelerated by CF(3)CO(2)H, and was not
      inhibited by CO. Selective deuteration of the RuH and OH positions in 8 gave
      individual kinetic isotope effects k(RuH)/k(RuD) = 1.5 +/- 0.2 and k(OH)/k(OD) =
      2.2 +/- 0.1 for PhCHO reduction at 0 degrees C. Simultaneous deuteration of both
      positions in 8 gave a combined kinetic isotope effect of k(OHRuH)/k(ODRuD) = 3.6
      +/- 0.3. [2,5-Ph(2)-3,4-Tol(2)(eta(5)-C(4)COSiEt(3))Ru(CO)(2)H] (12) and
      NEt(4)(+)[2,5-Ph(2)-3,4-Tol(2)(eta(4)-C(4)CO)Ru(CO)(2)H](-) (13) were unreactive
      toward PhCHO under conditions where facile PhCHO reduction by 8 occurred. PhCOMe
      was reduced by 8 30 times slower than PhCHO; MeN=CHPh was reduced by 8 26 times
      faster than PhCHO. Cyclohexene was reduced to cyclohexane by 8 at 80 degrees C
      only in the presence of H(2.) Concerted transfer of a proton from OH and hydride
      from Ru of 8 to carbonyls and imines is proposed.

PMID- 11456663
TI  - Two modes of linear layer-by-layer growth of nanoparticle--polylectrolyte
      multilayers and different interactions in the layer-by-layer deposition.
AB  - The structure of the multilayer assemblies of yttrium iron garnet nanoparticles
      (YIG) with polyelectrolytes was investigated with the emphasis on the control of
      the particle density in the adsorption layers. It was found that the growth of
      YIG films prepared by the layer-by-layer assembly can occur via two deposition
      modes: (1) sequential adsorption of densely packed adsorption layers (normal
      growth mode) and (2) in-plane growth of isolated particle domains (lateral
      expansion mode). Importantly, the dependence of the optical density on the number
      of deposition cycles remains linear in both cases. Microscopy results indicate
      that the origin of the lateral growth is in the interplay of particle/particle
      and particle/polyelectrolyte interactions rather than in a substrate effect. The
      lateral expansion mode is a general attribute of the layer-by-layer deposition
      and can be observed for various aqueous colloids. For the preparation of
      sophisticated multifunctional assemblies on nanoparticles, the film growth via
      domain expansion should be avoided, and therefore, one must be able to control
      the growth pattern. The switch from lateral to normal growth mode can be effected
      by grafting charged organic groups to YIG nanoparticles. Hydrophobic interactions
      between the hydrocarbon groups of the modified YIG and polyelectrolyte
      significantly increase the attractive component of the particle/polyelectrolyte
      and particle/particle interactions. The films from modified YIG display densely
      packed nanoparticle layers with a greatly reduced number of defects.

PMID- 11456664
TI  - Control of magnetic ordering by Jahn--Teller distortions in Nd(2)GaMnO(6) and
      La(2)GaMnO(6).
AB  - The substitution of Ga(3+) into the Jahn--Teller distorted, antiferromagnetic
      perovskites LaMnO(3) and NdMnO(3) strongly affects both the crystal structures
      and resulting magnetic ordering. In both compounds the Ga(3+) and Mn(3+) cations
      are disordered over the six coordinate sites. La(2)GaMnO(6) is a ferromagnetic
      insulator (T(c) = 70 K); a moment per Mn cation of 2.08(5) mu(B) has been
      determined by neutron powder diffraction at 5 K. Bond length and displacement
      parameter data suggest Jahn--Teller distortions which are both coherent and
      incoherent with the Pnma space group symmetry of the perovskite structure (a =
      5.51122(4) A, b = 7.80515(6) A, c = 5.52947(4) A) at room temperature. The
      coherent distortion is strongly suppressed in comparison with the parent LaMnO(3)
      phase, but the displacement ellipsoids suggest that incoherent distortions are
      significant and arise from local Jahn--Teller distortions. The preparation of the
      new phase Nd(2)GaMnO(6) has been found to depend on sample cooling rates, with
      detailed characterization necessary to ensure phase separation has been avoided.
      This compound also adopts the GdFeO(3)-type orthorhombically distorted perovskite
      structure (space group Pnma, a = 5.64876(1) A, b = 7.65212(2) A, c = 5.41943(1) A
      at room temperature). However, the B site substitution has a totally different
      effect on the Jahn--Teller distortion at the Mn(3+) centers. This phase exhibits
      a Q(2) mode Jahn--Teller distortion similar to that observed in LaMnO(3),
      although reduced in magnitude as a result of the introduction of Ga(3+) onto the
      B site. There is no evidence of a dynamic Jahn-Teller distortion. At 5 K a
      ferromagnetically ordered Nd(3+) moment of 1.06(6) mu(B) is aligned along the y
      axis and a moment of 2.8(1) mu(B) per Mn(3+) is ordered in the xy plane making an
      angle of 29(2) degrees with the y-axis. The Mn(3+) moments couple
      ferromagnetically in the xz plane. However, along the y-axis the moments couple
      ferromagnetically while the x components are coupled antiferromagnetically. This
      results in a canted antiferromagnetic arrangement in which the dominant exchange
      is ferromagnetic. Nd(2)GaMnO(6) is paramagnetic above 40(5) K, with a
      paramagnetic moment and Weiss constant of 6.70(2) mu(B) and 45.9(4) K,
      respectively. An ordered moment of 6.08(3) mu(B) per Nd(2)GaMnO(6) formula unit
      was measured by magnetometry at 5 K in an applied magnetic field of 5 T.

PMID- 11456665
TI  - A double-functionalized cyclen with carbamoyl and dansyl groups (cyclen =
      1,4,7,10-tetraazacyclododecane): a selective fluorescent probe for Y(3+) and
      La(3+).
AB  - A cyclen (=1,4,7,10-tetraazacyclododecane) doubly functionalized with three
      carbamoylmethyl groups and one dansylaminoethyl (dansyl = 2-(5-(dimethylamino)-1
      naphthalenesulfonyl) group (L(2) = 1-(2-(5-(dimethylamino)-1
      naphthalenesulfonylamido)ethyl)-4,7,10-tris(carbamoylmethyl)-cyclen) was
      synthesized and characterized. Potentiometrtic pH titration and UV
      spectrophotometric titration of L(2) served to determine deprotonation of the
      pendant dansylamide (L(2) --> H(-1)L(2)) with a pK(a) value of 10.6, while the
      fluorometric titration disclosed a pK(a) value of 8.8 +/- 0.2, which was assigned
      to the dansyl deprotonation in the excited state. The 1:1 M(3+)-H(-1)L(2)
      complexation constants (log K(app) = 6.0 for Y(3+) and 5.2 for La(3+), where
      K(app)(M-H(-1)L(2)) = [M(3+)-H(-1)L(2)]/[M(3+)](free)[L(2)](free) (M(-1)) at pH
      7.4) were determined by potentiometric pH titration and UV and fluorescence
      spectrophotometric titrations (excitation at 335 nm and emission at 520 nm) in
      aqueous solution (with I = 0.1 (NaNO(3))) and 25 degrees C. The X-ray structure
      analysis of the Y(3+)-H(-1)L complex showed nine-coordinated Y(3+) with four
      nitrogens of cyclen, three carbamoyl oxygens, and the deprotonated nitrogen and a
      sulfonyl oxygen of the dansylamide. The crystal data are as follow: formula
      C(28)H(49)N(11)O(13.5)SY (Y(3+)-H(-1)L(2) x 2(NO(3)(-)) x 2.5H(2)O), M(r) =
      876.73, monoclinic, space group P2(1)/n (No. 14), a = 18.912(3) A, b = 17.042(3)
      A, c = 24.318(4) A, beta = 95.99(1) degrees, V = 7794(2) A(3), Z = 8, R1 = 0.099.
      Upon M(3+)-H(-1)L(2) complexation, the dansyl fluorescence greatly increased (8.6
      and 3.8 times for Y(3+) and La(3+), respectively) in aqueous solution at pH 7.4.
      Other lanthanide ions also yielded Ln(3+)-H(-1)L(2) complexes with similar K(app)
      values, although all the dansyl fluorescences were weakly quenched. On the other
      hand, zinc(II) formed only a 1:1 Zn(2+)-L(2) complex at neutral pH with
      negligible fluorescence change. The X-ray crystal structure of the Zn(2+)-L(2)
      complex confirmed the pendant dansylamide being noncoordinating. The crystal data
      are as follow: formula C(28)H(51)N(11)O(14)SZn (Zn(2+)-L(2) x 2(NO(3)(-)) x
      3H(2)O), M(r) = 863.22, monoclinic, space group C2/n (No. 15), a = 35.361(1) A, b
      = 13.7298(5) A, c = 18.5998(6) A, beta = 119.073(2) degrees, V = 7892.3(5) A(3),
      Z = 8, R1 = 0.084. Other divalent metal ions did not interact with L(2) at all
      (e.g., Mg(2+) and Ca(2+)) or interacted with L(2) with the dansyl fluorescence
      quenched (e.g., Cu(2+)).

PMID- 11456666
TI  - Synthesis and characterization of alkanethiolate-coordinated iron porphyrins and
      their dioxygen adducts as models for the active center of cytochrome p450: direct
      evidence for hydrogen bonding to bound dioxygen.
AB  - Two kinds of novel cytochrome P450 models, which have alkanethiolate axial
      ligands and hydroxyl groups inside molecular cavities, were designed and
      synthesized as functional O(2) binding systems. A superstructured porphyrin,
      designated as "twin-coronet" porphyrin, was used as the common framework of the
      model complexes. This porphyrin bears four binaphthalene bridges on the both
      sides and forms two pockets surrounded by the bulky aromatic rings. Thiobenzyloxy
      and thioglycolate moieties, which contain an alkanethiolate group exhibiting
      various electron-donating abilities and degrees of bulkiness, were covalently
      linked to twin-coronet porphyrin to yield thiolate-coordinated hemes, TCP-TB and
      TCP-TG (twin-coronet porphyrin with thiobenzyloxy and thioglycolate groups),
      respectively. Both ferric complexes exhibited high stability during usual
      experimental manipulation under air and were characterized by MS, UV/vis, ESR
      spectroscopies, and CV. The ESR spectra exhibited low-spin signals (TCP-TB: g =
      2.334, 2.210, 1.959; TCP-TG: g = 2.313, 2.209, 1.966). The cyclic voltammogram of
      TCP-TB in CH(3)CN gave a quasi-reversible wave which corresponds to the
      Fe(III)/Fe(II) redox couple: E(p)()(/2) = -1.35 V (vs Fc/Fc(+)). On the other
      hand, TCP-TG showed a fine reversible wave: E(1/2) (Fe(III)/Fe(II)) = -1.12 V.
      The stable dioxygen adducts were formed in the reaction of the ferric complexes
      with KO(2) under an oxygen atmosphere and characterized by UV/vis and resonance
      Raman (RR) spectroscopies. In the RR spectra, the nu(O--O) bands of the dioxygen
      adducts were observed at 1138 cm(-1) (TCP-TB) and 1137 cm(-1) (TCP-TG). The
      hypothesis that hydrogen bonding between the bound oxygen and the hydroxyl groups
      of the binaphthyl moieties could increase their stability was verified by RR
      spectroscopy. When all hydroxyl groups were deuterated, only the frequencies of
      the nu(O--O) bands were upshifted by 2 cm(-1) without any perturbation in the
      porphyrin skeleton. This work shows the first direct evidence for a hydrogen bond
      to dioxygen in an oxy form of a thiolate-coordinated heme model system. These
      results are discussed in context of the process of dioxygen binding and
      activation in cytochrome P450.

PMID- 11456667
TI  - O atom transfer from nitric oxide catalyzed by Fe(TPP).
AB  - The reaction of NO-Fe(TPP) with low pressures of NO gas proceeds through three
      distinct transformations, the first of which we suggest is the formation of an N-
      N-coupled, (NO)(2) adduct intermediate. The subsequent formation of
      NO(NO(2))Fe(TPP), which under these conditions readily loses NO, suggests that it
      is formed by addition of free NO(2) to the starting nitrosyl. A mechanism is
      proposed which implies that the addition of a competitive O atom acceptor would
      lead to catalytic production of N(2)O. In agreement with the proposed mechanism,
      the formation of N(2)O is decoupled from the formation of the nitrite by using
      PPh(3) as the competitive acceptor. The mechanism of O atom transfer was examined
      by cross-labeling experiments, which show that both O atoms in the intermediate
      are equivalent, even under catalytic conditions. The formation of an intermediate
      was confirmed by IR spectroscopy of the heterogeneous reaction of an NO-Fe(TPP)
      film with gaseous NO, in which transient, isotope-sensitive nu(NO) bands are seen
      prior to NO(NO(2))Fe(TPP) formation. Mixed (14)N/(15)N label experiments
      demonstrate coupling between the two bound nitrosyls in the transient species.

PMID- 11456668
TI  - Layered rare-earth gallium antimonides REGaSb(2) (RE = La--Nd, Sm).
AB  - The ternary rare-earth gallium antimonides, REGaSb(2) (RE = La--Nd, Sm), have
      been synthesized through reaction of the elements. The structures of SmGaSb(2)
      (orthorhombic, space group D(5)(2)-C222(1), Z = 4, a = 4.3087(5) A, b = 22.093(4)
      A, c = 4.3319(4) A) and NdGaSb(2) (tetragonal, space group D(19)(4h)-I4(1)/amd, Z
      = 8, a = 4.3486(3) A, c = 44.579(8) A) have been determined by single-crystal X
      ray diffraction. The SmGaSb(2)-type structure is adopted for RE = La and Sm,
      whereas the NdGaSb(2)-type structure is adopted for RE = Ce--Nd. The layered
      SmGaSb(2) and NdGaSb(2) structures are stacking variants of each other. In both
      structures, two-dimensional layers of composition (2)(infinity)[GaSb] are
      separated from square nets of Sb atoms [Sb] by RE atoms. Alternatively, the
      structures may be considered as resulting from the insertion of zigzag Ga chains
      between (2)(infinity)[RE Sb(2)] slabs. In SmGaSb(2), all of the Ga chains are
      parallel and the (2)(infinity)[SmSb(2)] layers are stacked in a ZrSi(2)-type
      arrangement. In NdGaSb(2), the Ga chains alternate in direction, resulting in a
      doubling of the long axis relative to SmGaSb(2), and the (2)(infinity)[NdSb(2)]
      layers are stacked in a Zr(3)Al(4)Si(5)-type arrangement. Extended Huckel band
      structure calculations are used to explain the bonding in the [GaSb(2)](3-)
      substructure.

PMID- 11456669
TI  - Photoinduced electron transfer in hydrogen bonded donor--acceptor systems. Free
      energy and distance dependence studies and an analysis of the role of diffusion.
AB  - The free energy dependence of electron transfer in a few small-molecule donor-
      acceptor systems having hydrogen-bonding appendages was studied to evaluate the
      role of diffusion in masking the inverted region in bimolecular PET reactions. A
      small fraction of the probe molecules associate and this led to the simultaneous
      observation of unimolecular and diffusion-mediated quenching of the probe
      fluorescence. Free energy dependence studies showed that the unimolecular
      electron transfer obeys Marcus behavior and the diffusion-mediated electron
      transfer obeys Rehm--Weller behavior. The absence of an inverted region in
      bimolecular PET reactions is thus attributed to diffusion. The results of the
      free energy dependence studies suggest that distance dependence of electron
      transfer plays a role in masking the inverted region. To ascertain this aspect we
      have carried out a study of the distance dependence of electron transfer in the
      hydrogen-bonded donor--acceptor systems. For a system in the normal region an
      exponential rate decrease was observed. For a system in the inverted region it
      was observed that the rate depends very feebly on distance. Thus distance
      dependence studies did not confirm the prediction of enhanced rates at larger
      distances in the inverted region.

PMID- 11456670
TI  - CO oxidation on Pd(100) and Pd(111): a comparative study of reaction pathways and
      reactivity at low and medium coverages.
AB  - We have performed density functional theory calculations with the generalized
      gradient approximation to investigate CO oxidation on a close-packed transition
      metal surface, Pd(111), and a more open surface, Pd(100), aiming to shed light on
      surface structure effects on reaction pathways and reactivity, an important issue
      in catalysis. Reaction pathways on both surfaces at two different coverages have
      been studied. It is found that the reaction pathways on both surfaces possess
      crucial common features despite the fact that they have different surface
      symmetries. Having determined reaction barriers in these systems, we find that
      the reaction on Pd(111) is strongly coverage dependent. Surface coverages,
      however, have little effect on the reaction on Pd(100). Calculations also reveal
      that the low coverage reactions are structure sensitive while the medium coverage
      reactions are not. Detailed discussions on these results are given.

PMID- 11456671
TI  - Predicting the activity of phenolic antioxidants: theoretical method, analysis of
      substituent effects, and application to major families of antioxidants.
AB  - A procedure based on density functional theory is used for the calculation of the
      gas-phase bond dissociation enthalpy (BDE) and ionization potential for molecules
      belonging to the class of phenolic antioxidants. We show that use of locally
      dense basis sets (LDBS) vs full basis sets gives very similar results for
      monosubstituted phenols, and that the LDBS procedure gives good agreement with
      the change in experimental BDE values for highly substituted phenols in benzene
      solvent. Procedures for estimating the O--H BDE based on group additivity rules
      are given and tested. Several interesting classes of phenolic antioxidants are
      studied with these methods, including commercial antioxidants used as food
      additives, compounds related to Vitamin E, flavonoids in tea, aminophenols,
      stilbenes related to resveratrol, and sterically hindered phenols. On the basis
      of these results we are able to interpret relative rates for the reaction of
      antioxidants with free radicals, including a comparison of both H-atom-transfer
      and single-electron-transfer mechanisms, and conclude that in most cases H-atom
      transfer will be dominant.

PMID- 11456672
TI  - N-terminal derivatization and fragmentation of neutral peptides via ion--molecule
      reactions with acylium ions: toward gas-phase Edman degradation?
AB  - The gas-phase ion-molecule reactions of neutral alanylglycine have been examined
      with various mass-selected acylium ions RCO(+) (R= CH(3), CD(3), C(6)H(5),
      C(6)F(5) and (CH(3))( 2)N), as well as the transacylation reagent O
      benzoylbenzophenone in a Fourier transform ion cyclotron resonance mass
      spectrometer. Reactions of the gaseous dipeptide with acylium ions trapped in the
      ICR cell result in the formation of energized [M + RCO](+) adduct ions that
      fragment to yield N-terminal b-type and C-terminal y-type product ions, including
      a modified b(1) ion which is typically not observed in the fragmentation of
      protonated peptides. Judicious choice of the acylium ion employed allows some
      control over the product ion types that are observed (i.e., b versus y ions). The
      product ion distributions from these ion--molecule reactions are similar to those
      obtained by collision-activated dissociation in a triple quadrupole mass
      spectrometer of the authentic N-acylated alanylglycine derivatives. These data
      indicate that derivatization of the peptide in the gas-phase occurs at the N
      terminal amine. Ab initio molecular orbital calculations, performed to estimate
      the thermochemistry of the steps associated with adduct formation as well as
      product ion formation, indicate that (i) the initially formed adduct is energized
      and hence likely to rapidly undergo fragmentation, and (ii) the likelihood for
      the formation of modified b(1) ions in preference to y(1) ions is dependent on
      the R substituent of the acylium ion. The reaction of the tetrapeptide valine-
      alanine--alanine--phenylalanine with the benzoyl cation was also found to yield a
      number of product ions, including a modified b(1) ion. This result suggests that
      the new experimental approach described here may provide a tool to address one of
      the major limitations associated with traditional mass spectrometric peptide
      sequencing approaches, that is, determination of the identity and order of the
      two N-terminal amino acids. Analogies are made between the reactions observed
      here and the derivatization and N-terminal cleavage reactions employed in the
      condensed-phase Edman degradation method.

PMID- 11456673
TI  - Orbital phase control of the preferential branching of chain molecules.
AB  - The orbital phase theory was applied to the stabilities of the branched isomers
      (1) of E(4)H(10) (E = C, Si, Ge, Sn) relative to the normal ones (2). The orbital
      phase prediction was confirmed by ab initio molecular orbital (MO) and density
      functional theory (DFT) calculations as well as by some experimental results.
      Further applications to the relative stabilities of other alkane and alkene
      isomers lead to the preference of the branched to the normal isomers, the
      neopentane-type to isobutane-type branching, the terminal to inner methyl
      branching, and the methyl to ethyl inner substitution in the longer alkanes, as
      well as the preference of isobutene to 2-butene moieties. The preferential
      stabilization of the branched isomers was shown to be general and controlled by
      the orbital phase.

PMID- 11456674
TI  - Photopolymerization of liquid carbon disulfide produces nanoscale polythiene
      films.
AB  - Broad band solar or 300--400 nm irradiation (Hg--Xe arc source) of liquid-phase
      carbon disulfide produces a new carbon--sulfur polymer with the approximate (n =
      1.04--1.05) stoichiometry (CS(n))(x). The polymer, from here on called (CS)(x),
      forms as a approximately 200 nm thick transparent golden membrane as measured by
      SEM and AFM techniques. IR spectra for this polymer show some similarities with
      those obtained for the gas-phase photopolymerized (CS(2))(x) and the high
      pressure-phase polymer of CS(2), called Bridgman's Black. The observed FT-IR
      absorptions of (CS)(x) include prominent features at 1431 (s, br), 1298 (m), 1250
      (ms), and 1070 cm(-1) (m). In contrast to previous proposals for (CS(2))(x),
      (13)C labeling and model compound studies of alpha-(C(3)S(5))R(2) and beta
      (C(3)S(5))R(2) (R = methyl or benzoyl) suggest that the absorption at 1431 cm(-1)
      and those at 1298 and 1250 cm(-1) are indicative of carbon--carbon double bonds
      and carbon--carbon single bonds, respectively. The molecular structure of alpha
      (C(3)S(5))(C(O)C(6)H(5))(2), determined at -84 degrees C, belongs to space group
      P1, with a = 7.486(5) A, b = 13.335(11) A, c = 17.830(13) A, alpha = 105.60(6)
      degrees, beta = 95.32(6) degrees, gamma = 90.46(6) degrees, Z = 4, V = 1706(2)
      A(3), R = 0.0785, and R(w) = 0.2323. With use of electron and chemical ionization
      mass spectrometry, C(4)S(6) and C(6)S(7) were identified as the dominant soluble
      molecular side-products derived from a putative ethylenedithione (S==C==C==S)
      precursor. Atomic force microscopy (AFM) provided surface topology information
      for the thin film (CS)(x) and revealed features that suggested the bulk material
      is formed from small polymer spheres 20--50 nm in size. Both (CS(2))(x) and
      (CS)(x) are extensively cross-linked through disulfide linkages and both
      materials show strong EPR resonances (g > 2.006) indicative of sulfur-centered
      radicals from incomplete cross-linking. A polymerization mechanism based on the
      intermediacy of S(2)C=CS(2) is proposed.

PMID- 11456675
TI  - Sites of hydroxyl radical reaction with amino acids identified by (2)H NMR
      detection of induced (1)H/(2)H exchange.
AB  - Hydroxyl radical reacts with the aliphatic C-H bonds of amino acids by H atom
      abstraction. Under anaerobic conditions inclusion of a (2)H atom donor results in
      (1)H/(2)H exchange into these C-H bonds [Goshe et al. Biochemistry 2000, 39, 1761
      -1770]. The site of (1)H/(2)H exchange can be detected and quantified by (2)H
      NMR. Integration of the (2)H NMR resonances within a single spectrum permits the
      relative rate of H atom abstraction from each position to be determined. Analysis
      of the aliphatic amino acid spectra indicates that the methine and methylene
      positions were more reactive than the methyl positions. The (2)H NMR spectra of
      isoleucine and leucine show that H-atom abstraction distal to the alpha-carbon
      occurs preferentially. Significant (1)H/(2)H exchange was observed into the delta
      positions of proline and arginine and into the epsilon-methylene of lysine,
      indicating that a positive charge on a geminal N does not inhibit the (1)H/(2)H
      exchange. Comparisons of (2)H NMR integrations between amino acid spectra
      indicated that (1)H/(2)H exchange occurred in the following descending order: L >
      I > V > R > K > Y > P > H > F >M> T > A > [C, S, D, N, E, Q, G, W]. The extent of
      (1)H/(2)H exchange into methionine, N-glycyl-methionine, and methionine sulfoxide
      suggests that a prominent solvent exchange pathway involving hydroxyl radical
      mediated oxidation of methionine exists to account for the large (2)H
      incorporation into the gamma-methylene of methionine sulfoxide that is absent for
      N-glycyl-methionine. Analysis of the (1)H NMR spectra of the reactions with
      phenylalanine and tyrosine indicated that hydroxyl radical addition to the phenyl
      ring under the anaerobic reductive reaction conditions did not result in either
      exchange or hydroxylation.

PMID- 11456676
TI  - Two-photon photosensitized production of singlet oxygen.
AB  - Singlet molecular oxygen (a(1)Delta(g)) has been produced and optically detected
      upon two-photon nonlinear excitation of a sensitizer with a focused laser beam.
      The experiments were performed using toluene solutions with either a substituted
      difuranonaphthalene or a substituted distyryl benzene as the sensitizer. The data
      indicate that the two-photon absorption cross sections of the
      difuranonaphthalenes are comparatively large and depend significantly on the
      functional groups attached to the chromophore. The time-resolved 1270 nm
      phosphorescence signals used to characterize the production of singlet oxygen are
      limited in much the same way as signals from other two-photon spectroscopic
      studies (e.g., weak signals that can be masked by scattered radiation).
      Nevertheless, the two-photon singlet oxygen signals also reflect the unique
      advantages of this nonlinear optical technique (e.g., depth penetration in the
      sample afforded by irradiation in a spectral region void of the more dominant one
      photon linear transitions and spatial resolution afforded by irradiation with a
      focused laser beam).

PMID- 11456677
TI  - Protein structural motif recognition via NMR residual dipolar couplings.
AB  - NMR residual dipolar couplings have great potential to provide rapid structural
      information for proteins in the solution state. This information even at low
      resolution may be used to advantage in proteomics projects that seek to annotate
      large numbers of gene products for entire genomes. In this paper, we describe a
      novel approach to the structural interpretation of dipolar couplings which is
      based on structural motif pattern recognition, where a predefined gapless
      structural template for a motif is used to search a set of residual dipolar
      couplings for good matches. We demonstrate the applicability of the method using
      synthetic and experimental data. We also provide an analysis of the statistical
      power of the method and the effects of order tensor frame orientation, motif
      size, and structural complexity on motif detection. Finally, we discuss remaining
      problems that must be overcome before the method can be used routinely to
      identify protein homologies.

PMID- 11456678
TI  - Atom economy: aldol-type products by vanadium-catalyzed additions of propargyl
      alcohols and aldehydes.

PMID- 11456679
TI  - Reductive elimination of aryl halides from palladium(II).

PMID- 11456680
TI  - Regioselective rhodium-catalyzed allylic linchpin cross-coupling reactions:
      diastereospecific construction of anti-1,3-carbon stereogenic centers and C(2)
      symmetrical fragments.

PMID- 11456681
TI  - Proton-coupled electron transfer in duplex DNA: driving force dependence and
      isotope effects on electrocatalytic oxidation of guanine.

PMID- 11456682
TI  - New approach to multiply deuterated isoprenoids using triply engineered
      Escherichia coli and its potential as a tool for mechanistic enzymology.

PMID- 11456683
TI  - Macroscopic shear alignment of bulk transparent mesostructured silica.

PMID- 11456684
TI  - Ketone isosteres of 2-N-acetamidosugars as substrates for metabolic cell surface
      engineering.

PMID- 11456685
TI  - Beyond the hydrophobic effect: attractions involving heteroaromatic rings in
      aqueous solution.

PMID- 11456686
TI  - Template synthesis of asymmetrically mesostructured platinum networks.

PMID- 11456687
TI  - Controlled placement of luminescent molecules and polymers in mesostructured sol-
      gel thin films.

PMID- 11456688
TI  - Electronic structure of the pentacene single crystal: relation to transport
      properties.

PMID- 11456689
TI  - Measuring the size and charge of proteins using protein charge ladders, capillary
      electrophoresis, and electrokinetic models of colloids.

PMID- 11456690
TI  - Asymmetric hydrogenation and catalyst recycling using ionic liquid and
      supercritical carbon dioxide.

PMID- 11456691
TI  - Novel multiaction of Zr catalyst: one-pot synthesis of beta-cyanohydrins from
      olefins.

PMID- 11456692
TI  - A double-walled hexagonal supermolecule assembled by guest binding.

PMID- 11456693
TI  - Fluorescent chemosensors based on conformational restriction of a biaryl
      fluorophore.

PMID- 11456694
TI  - Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus.

PMID- 11456695
TI  - Preferential heterodimer formation via undercompensated electrostatic
      interactions.

PMID- 11456697
TI  - Stability and structure of RNA duplexes containing isoguanosine and isocytidine.
AB  - Isoguanosine (iG) and isocytidine (iC) differ from guanosine (G) and cytidine
      (C), respectively, in that the amino and carbonyl groups are transposed. The
      thermodynamic properties of a set of iG, iC containing RNA duplexes have been
      measured by UV optical melting. It is found that iG-iC replacements usually
      stabilize duplexes, and the stabilization per iG-iC pair is sequence-dependent.
      The sequence dependence can be fit to a nearest-neighbor model in which the
      stabilities of iG--iC pairs depend on the adjacent iG--iC or G--C pairs. For 5'
      CG-3'/3'-GC-5' and 5'-GG-3'/3'-CC-5' nearest neighbors, the free energy
      differences upon iG-iC replacement are smaller than 0.2 kcal/mol at 37 degrees C,
      regardless of the number of replacements. For 5'-GC-3'/3'-CG-5', however, each iG
      -iC replacement adds 0.6 kcal/mol stabilizing free energy at 37 degrees C.
      Stacking propensities of iG and iC as unpaired nucleotides at the end of a duplex
      are similar to those of G and C. An NMR structure is reported for r(CiGCGiCG)(2)
      and found to belong to the A-form family. The structure has substantial
      deviations from standard A-form but is similar to published NMR and/or crystal
      structures for r(CGCGCG)(2) and 2'-O-methyl (CGCGCG)(2). These results provide
      benchmarks for theoretical calculations aimed at understanding the fundamental
      physical basis for the thermodynamic stabilities of nucleic acid duplexes.

PMID- 11456698
TI  - Inhibition of cell adhesion to fibronectin by oligopeptide-substituted
      polynorbornenes.
AB  - Polynorbornenes substituted with two different peptide sequences from the RGD
      containing integrin cell-binding domain of fibronectin are potent inhibitors of
      human foreskin fibroblast cell adhesion to fibronectin-coated surfaces. Ring
      opening metathesis polymerization (ROMP) using Ru==CHPh(Cl)(2)(PCy(3))(DHIMes)
      (1) as an initiator produced polymers substituted with GRGDS and PHSRN peptide
      sequences. The inhibitory activity was quantified for these polymers and compared
      to the free peptides and GRGES-containing controls. A homopolymer substituted
      with GRGDS peptides was significantly more active than the free GRGDS peptide
      (IC(50) of 0.18 +/- 0.03 and 1.33 +/- 0.20 mM respectively), and the copolymer
      containing both GRGDS and PHSRN is the most potent inhibitor (IC(50) of 0.04 +/-
      0.01 mM). These results demonstrate that significant enhancements of observed
      biological activity can be obtained from polymeric materials containing more than
      one type of multivalent ligand and that ROMP is a useful method to synthesize
      such well-defined copolymers.

PMID- 11456699
TI  - Identification of a novel class of small-molecule antiangiogenic agents through
      the screening of combinatorial libraries which function by inhibiting the binding
      and localization of proteinase MMP2 to integrin alpha(V)beta(3).
AB  - The process of new blood vessel growth from existing vasculature, known as
      angiogenesis, is critical to several pathological conditions, most notably
      cancer. Both MMP2, which degrades the extracellular matrix (ECM), and integrin
      alpha(V)beta(3), which contributes to endothelial cell attachment to the ECM, are
      critically involved in this process. Recent findings have shown that MMP2 is
      localized in an active form on the surface of invasive endothelial cells based on
      its ability to directly bind integrin alpha(V)beta(3), suggesting that disrupting
      this protein--protein interaction may represent a new target for the development
      of angiogenesis inhibitors. The screening of small molecule libraries led to the
      identification of compounds which disrupt the MMP2--alpha(V)beta(3) interaction
      in an in vitro binding assay. A prototypical inhibitor was further found to
      prevent the degradation of the protein matrix without directly inhibiting MMP2
      activity or disrupting the binding of alpha(V)beta(3) to its classical ECM
      ligand, vitronectin. The synthesis and screening of analogues and substructures
      of this lead compound allowed the identification of requisite structural features
      for inhibition of MMP2 binding to alpha(V)beta(3). This led to the synthesis of a
      more water-soluble derivative which maintains the in vitro biological properties
      and has potent antiangiogenic and antitumor activity in vivo, validating the
      target as one useful for therapeutic intervention.

PMID- 11456703
TI  - Kinetic analysis of the stepwise formation of a long-range DNA interstrand cross
      link by a dinuclear platinum antitumor complex: evidence for aquated
      intermediates and formation of both kinetically and thermodynamically controlled
      conformers.
AB  - Reported here is a detailed study of the kinetics and mechanism of formation of a
      1,4 GG interstrand cross-link by [(trans-PtCl(NH(3))(2))(2)(mu
      NH(2)(CH(2))(n)NH(2))](2+) (1,1/t,t (n = 6), 1), the prototype of a novel class
      of platinum antitumor complexes. The reaction of the self-complementary 12-mer
      duplex 5'-[d(ATATGTACATAT)(2)] with (15)N-1 has been studied at 298 K, pH 5.4, by
      [(1)H,(15)N] HSQC 2D NMR spectroscopy. Initial electrostatic interactions with
      the duplex are observed for 1 and the monoaqua monochloro species (2). Aquation
      of 1 to yield 2 occurs with a pseudo-first-order rate constant of (4.15 +/- 0.04)
      x 10(-5) s(-1). 2 then undergoes monofunctional binding to the guanine N7 of the
      duplex to form 3 (G/Cl) with a rate constant of 0.47 +/- 0.06 M(-(1) s(-1). There
      is an electrostatic interaction between the unbound [PtN(3)Cl] group of 3 and the
      duplex, which is consistent with H-bonding interactions observed in the molecular
      model of the monofunctional (G/Cl) adduct. Closure of 3 to form the 1,4 GG
      interstrand cross-link (5) most likely proceeds via the aquated (G/H(2)O)
      intermediate (4) (pseudo-first-order rate constant = (3.62 +/- 0.04) x 10(-5) s(
      1)) followed by closure of 4 to form 5 (rate constant = (2.7 +/- 1.5) x 10(-3) s(
      1)). When closure is treated as direct from 3 (G/Cl) the rate constant is (3.39
      +/- 0.04) x 10(-5) s(-1). Closure is ca. 10-55-fold faster than that found for
      1,2 GG intrastrand cross-link formation by the diaqua form of cisplatin. Changes
      in the (1)H and (15)N shifts of the interstrand cross-link 5 indicate that the
      initially formed conformer (5(i)) converts irreversibly into other product
      conformer(s) 5(f). The NMR data for 5(i) are consistent with a molecular model of
      the 1,4 GG interstrand cross-link on B-form DNA, which shows that the NH(2)
      protons have no contacts except with solvent. The NMR data for 5(f) show several
      distinct NH(2) environments indicative of interactions between the NH(2) protons
      and the DNA. HPLC characterization of the final product showed only one major
      product peak that was confirmed by ESI-FTICR mass spectroscopy to be a cross
      linked adduct of (15)N-1 and the duplex. The potential significance of these
      findings to the antitumor activity of dinuclear platinum complexes is discussed.

PMID- 11456704
TI  - Conformational equilibrium isotope effects in glucose by (13)C NMR spectroscopy
      and computational studies.
AB  - Anomeric equilibrium isotope effects for dissolved sugars are required preludes
      to understanding isotope effects for these molecules bound to enzymes. This paper
      presents a full molecule study of the alpha- and beta-anomeric forms of D
      glucopyranose in water using deuterium conformational equilibrium isotope effects
      (CEIE). Using 1D (13)C NMR, we have found deuterium isotope effects of 1.043 +/-
      0.004, 1.027 +/- 0.005, 1.027 +/- 0.004, 1.001 +/- 0.003, 1.036 +/- 0.004, and
      0.998 +/- 0.004 on the equilibrium constant, (H/D)K(beta/alpha), in [1-(2)H]-, [2
      (2)H]-, [3-(2)H]-, [4-(2)H]-, [5-(2)H]-, and [6,6'-(2)H(2)]-labeled sugars,
      respectively. A computational study of the anomeric equilibrium in glucose using
      semiempirical and ab initio methods yields values that correlate well with
      experiment. Natural bond orbital (NBO) analysis of glucose and dihedral
      rotational equilibrium isotope effects in 2-propanol strongly imply a
      hyperconjugative mechanism for the isotope effects at H1 and H2. We conclude that
      the isotope effect at H1 is due to n(p) --> sigma* hyperconjugative transfer from
      O5 to the axial C1--H1 bond in beta-glucose, while this transfer makes no
      contribution to the isotope effect at H5. The isotope effect at H2 is due to
      rotational restriction of OH2 at 160 degrees in the alpha form and 60 degrees in
      the beta-sugar, with concomitant differences in n --> sigma* hyperconjugative
      transfer from O2 to CH2. The isotope effects on H3 and H5 result primarily from
      syn-diaxial steric repulsion between these and the axial anomeric hydroxyl oxygen
      in alpha-glucose. Therefore, intramolecular effects play an important role in
      isotopic perturbation of the anomeric equilibrium. The possible role of
      intermolecular effects is discussed in the context of recent molecular dynamics
      studies on aqueous glucose.

PMID- 11456705
TI  - The peroxidase activity of a hemin--DNA oligonucleotide complex: free radical
      damage to specific guanine bases of the DNA.
AB  - A specific DNA oligonucleotide--hemin complex (PS2.M--hemin complex) that
      exhibits DNA-enhanced peroxidative activity was studied by EPR and UV--visible
      spectroscopy and by chemical probing analysis. EPR data obtained from low
      temperature experiments on the PS2.M--hemin complex showed both a low-field g
      approximately 6 and a high-field g approximately 2 signal. These EPR signals are
      typical of high-spin ferric heme with axial symmetry as judged by the EPR
      spectrum of six-coordinate heme iron in acidic Fe(III)-myoglobin. This similarity
      is consistent with the presence of two axial ligands to the heme iron within the
      PS2.M--hemin complex, one of which is a water molecule. Optical analyses of the
      acid-base transition for the hemin complex yielded a pK(a) value for the water
      ligand of 8.70 +/- 0.03 (mean +/- SD). Low-temperature EPR analysis coupled with
      parallel spin-trapping investigations following the reaction of the PS2.M--hemin
      complex and hydrogen peroxide (H(2)O(2)) indicated the formation of a carbon
      centered radical, most likely on the PS2.M oligonucleotide. Chemical probing
      analysis identified specific guanine bases within the PS2.M sequence that
      underwent oxidative damage upon reaction with H(2)O(2). These and other
      experimental findings support the hypothesis that the interaction of specific
      guanines of PS2.M with the bound hemin cofactor might contribute to the superior
      peroxidative activity of the PS2.M--hemin complex.

PMID- 11456709
TI  - Total synthesis and structural elucidation of khafrefungin.
AB  - Total synthesis and structural elucidation of khafrefungin, a novel antifungal
      agent isolated from the fermentation culture MF6020, have been achieved. Unlike
      other inhibitors that inhibit the corresponding enzyme in fungi and mammals to
      the same extent, khafrefungin does not impair sphingolipid synthesis of mammals.
      The basic strategy for the structural elucidation is to prepare all stereoisomers
      of the structurally simplified khafrefungin mimics 1 and 2 that were designed for
      the elucidation of C10,11,12 and C2',3',4' relative stereochemistry,
      respectively. The comparison of their spectra with those of natural khafrefungin
      would result in the identification of eight possible stereoisomers, and the
      analytical details of these eight stereoisomers have led to the complete
      stereochemical assignment. On the basis of the structural elucidation, the total
      synthesis of khafrefungin has been accomplished by using tin(II)-catalyzed
      asymmetric aldol reactions as key steps.

PMID- 11456714
TI  - Hydroxylation of camphor by reduced oxy-cytochrome P450cam: mechanistic
      implications of EPR and ENDOR studies of catalytic intermediates in native and
      mutant enzymes.
AB  - We have employed gamma-irradiation at cryogenic temperatures (77 K and also
      approximately 6 K) of the ternary complexes of camphor, dioxygen, and ferro
      cytochrome P450cam to inject the "second" electron of the catalytic process. We
      have used EPR and ENDOR spectroscopies to characterize the primary product of
      reduction as well as subsequent states created by annealing reduced oxyP450, both
      the WT enzyme and the D251N and T252A mutants, at progressively higher
      temperatures. (i) The primary product upon reduction of oxyP450 4 is the end-on,
      "H-bonded peroxo" intermediate 5A. (ii) This converts even at cryogenic
      temperatures to the hydroperoxo-ferriheme species, 5B, in a step that is
      sensitive to these mutations. Yields of 5B are as high as 40%. (iii) In WT and
      D251N P450s, brief annealing in a narrow temperature range around 200 K causes 5B
      to convert to a product state, 7A, in which the product 5-exo-hydroxycamphor is
      coordinated to the ferriheme in a nonequilibrium configuration. Chemical and EPR
      quantitations indicate the reaction pathway involving 5B yields 5-exo
      hydroxycamphor quantitatively. Analogous (but less extensive) results are seen
      for the alternate substrate, adamantane. (iv) Although the T252A mutation does
      not interfere with the formation of 5B, the cryoreduced oxyT252A does not yield
      product, which suggests that 5B is a key intermediate at or near the branch-point
      that leads either to product formation or to nonproductive "uncoupling" and
      H(2)O(2) production. The D251N mutation appears to perturb multiple stages in the
      catalytic cycle. (v) There is no spectroscopic evidence for the buildup of a high
      valence oxyferryl/porphyrin pi-cation radical intermediate, 6. However, ENDOR
      spectroscopy of 7A in H(2)O and D(2)O buffers shows that 7A contains
      hydroxycamphor, rather than water, bound to Fe(3+), and that the proton removed
      from the C(5) carbon of substrate during hydroxylation is trapped as the hydroxyl
      proton. This demonstrates that hydroxylation of substrates by P450cam in fact
      occurs by the formation and reaction of 6. (vi) Annealing at > or = 220 K
      converts the initial product state 7A to the equilibrium product state 7, with
      the transition occurring via a second nonequilibrium product state, 7B, in the
      D251N mutant; in states 7B and 7 the hydroxycamphor hydroxyl proton no longer is
      trapped. (vii) The present results are discussed in the context of other efforts
      to detect intermediates in the P450 catalytic cycle.

PMID- 11456715
TI  - Structural and dynamic analysis of residual dipolar coupling data for proteins.
AB  - The measurement of residual dipolar couplings in weakly aligned proteins can
      potentially provide unique information on their structure and dynamics in the
      solution state. The challenge is to extract the information of interest from the
      measurements, which normally reflect a convolution of the structural and dynamic
      properties. We discuss here a formalism which allows a first order separation of
      their effects, and thus, a simultaneous extraction of structural and motional
      parameters from residual dipolar coupling data. We introduce some terminology,
      namely a generalized degree of order, which is necessary for a meaningful
      discussion of the effects of motion on residual dipolar coupling measurements. We
      also illustrate this new methodology using an extensive set of residual dipolar
      coupling measurements made on (15)N,(13)C-labeled human ubiquitin solvated in a
      dilute bicelle solution. Our results support a solution structure of ubiquitin
      which on average agrees well with the X-ray structure (Vijay-Kumar, et al., J.
      Mol. Biol. 1987, 194, 531--544) for the protein core. However, the data are also
      consistent with a dynamic model of ubiquitin, exhibiting variable amplitudes, and
      anisotropy, of internal motions. This work suggests the possibility of primary
      use of residual dipolar couplings in characterizing both structure and
      anisotropic internal motions of proteins in the solution state.

PMID- 11456724
TI  - Large anhydrous polyalanine ions: evidence for extended helices and onset of a
      more compact state.
AB  - Ion mobility measurements and molecular modeling calculations have been used to
      examine the conformations of large multiply charged polyalanine peptides. Two
      series of [Ala(n)+3H](3+) conformations which do not interconvert during the 10
      to 30 ms experimental timescales are observed: a family of elongated structures
      for n = 18 to 39 and a series of more compact conformations for n = 24 to 41. The
      more compact state becomes the dominant conformer type for n > 32. Molecular
      modeling studies and comparisons of calculated collision cross sections with
      experiment indicate that the elongated ions have extended helical conformations.
      We suggest that the more compact state corresponds to a new conformer type: a
      folded hinged helix-coil state in which helical and coil regions have similar
      physical dimensions. The competition between extended and compact states is
      rationalized by considering differences in charge stabilization and entropy.

PMID- 11456731
TI  - Matrix-assisted biomimetic assembly of ferritin core analogues in organosilica
      sol--gels.

PMID- 11456732
TI  - "Hangman" porphyrins for the assembly of a model heme water channel.

PMID- 11456734
TI  - A novel europium(III)-based MRI contrast agent.

PMID- 11456736
TI  - A subtype-selective thyromimetic designed to bind a mutant thyroid hormone
      receptor implicated in resistance to thyroid hormone.

PMID- 11456737
TI  - Design, synthesis, and evaluation of the transition- state inhibitors of
      coelenterazine bioluminescence: probing the chiral environment of active site.

PMID- 11456738
TI  - An inhibitor of the interaction of thyroid hormone receptor beta and
      glucocorticoid interacting protein 1.

PMID- 11456739
TI  - Site-specific incorporation of nitroxide spin-labels into internal sites of the
      TAR RNA; structure-dependent dynamics of RNA by EPR spectroscopy.

PMID- 11456741
TI  - Catalytic, asymmetric alpha-halogenation.

PMID- 11456742
TI  - Asymmetric total synthesis of (-)-isolaurallene.

PMID- 11456744
TI  - Phospholipid bicelles with positive anisotropy of the magnetic susceptibility.

PMID- 11456746
TI  - Determination of protein backbone structure using only residual dipolar
      couplings.

PMID- 11456747
TI  - Theoretical modeling of putative Ni(III)--F(430) intermediates of methylcoenzyme
      M reductase.

PMID- 11456752
TI  - Highly stereoselective reagents for beta-keto ester reductions by genetic
      engineering of baker's yeast.
AB  - While whole cells of baker's yeast (Saccharomyces cerevisiae) are a convenient
      biocatalytic reducing agent for a wide variety of carbonyl compounds, mixtures of
      stereoisomeric alcohols are often observed since the organism contains a large
      number of reductase enzymes with overlapping substrate specificities but
      differing stereoselectivities. We sought to improve the performance of baker's
      yeast for beta-keto ester reductions by using recombinant DNA techniques to alter
      the levels of three enzymes known to play important roles in these reactions
      (fatty acid synthase, Fasp; aldo-keto reductase, Ypr1p; alpha-acetoxy ketone
      reductase, Gre2p). A complete set of "first-generation" yeast strains that either
      lack or overexpress each of these three enzymes was created and tested for
      improvements in stereoselective reductions of a series of beta-keto esters. On
      the basis of these results, multiply modified ("second-generation") strains were
      created that combined gene knockout and overexpression in single strains. In some
      cases, these additional modifications further improved the stereoselectivities of
      beta-keto ester reductions, thereby making several beta-hydroxy ester building
      blocks readily available by reactions that can be performed by nonspecialists.
      This work also revealed that additional yeast proteins participate in reducing
      beta-keto esters, and further progress using this strategy will require either
      additional genetic manipulations or the expression of yeast reductases in hosts
      that lack enzymes with overlapping substrate specificity.

PMID- 11456753
TI  - Bridging the gap between proteins and nucleic acids: a metal-independent RNAseA
      mimic with two protein-like functionalities.
AB  - Two synthetically modified nucleoside triphosphate analogues (adenosine modified
      with an imidazole and uridine modified with a cationic amine) are enzymatically
      polymerized in tandem along a degenerate DNA library for the combinatorial
      selection of an RNAse A mimic. The selected activity is consistent with both
      electrostatic and general acid/base catalysis at physiological pH in the absence
      of divalent metal cations. The simultaneous use of two modified nucleotides to
      enrich the catalytic repertoire of DNA-based catalysts has never before been
      demonstrated and evidence of general acid/base catalysis at pH 7.4 for a DNAzyme
      has never been previously observed in the absence of a divalent metal cation or
      added cofactor. This work illustrates how the incorporation of protein-like
      functionalities in nucleic acids can bridge the gap between proteins and
      oligonucleotides underscoring the potential for using nucleic acid scaffolds in
      the development of new materials and improved catalysts for use in chemistry and
      medicine.

PMID- 11456754
TI  - Correlation of relative rates of PdCl(2) oxidation of functionalized acyclic
      alkenes versus alkene ionization potentials, HOMOs, and LUMOs.
AB  - Investigations of the title reaction, carried out by plotting logs of the
      relative reaction rates vs IPs, vs HOMOs, and vs LUMOs, reveal multiple nearly
      parallel lines of correlation with small negative slopes in each. Overall, the
      natural grouping into monosubstituted and disubstituted alkenes gives better
      correlations than that obtained by using all alkenes. Comparison with analogous
      plots for other reactions indicates that the mechanism for this reaction has
      similarities to that for hydroboration, the major difference being that the lines
      in the plots for hydroboration have positive slopes, indicating an electrophilic
      rate-determining step involving the pi electrons, while those for the title
      reaction have small negative slopes, indicating a nucleophilic rate-determining
      step. Of the two reaction mechanisms proposed for the title reaction, only one
      has a nucleophilic attack at the complexed alkene as the rate-determining step,
      and therefore, this work supports that reaction mechanism.

PMID- 11456755
TI  - The bicyclo[2.2.2]octyl carbene system as a probe for migratory aptitudes of
      hydrogen to carbenic centers.
AB  - A series of tosylhydrazone derivatives of exo-6-substituted bicylo[2.2.2]octan-2
      ones have been prepared. Thermal decomposition of the sodium salts of these
      tosylhydrazones gives carbene-derived products from 1,3-migration of either the
      C6 hydrogen (perturbed) or the C7 hydrogen (unperturbed), along with smaller
      amounts of alkenes derived from 1,2-hydrogen migration. The exo-6-substituent
      strongly activates 1,3-hydrogen migration in the case of SiMe(3) and weakly
      activates it in the case of CH(3) substitution. Thiomethoxy and carbomethoxy are
      weakly deactivating, while cyano and methoxy groups are strongly deactivating.
      B3LYP/6-31G* calculations on these substituted carbenes and transition states are
      in qualitative agreement with the ease of 1,3-hydrogen migration of perturbed vs
      unperturbed hydrogen. These experimental results and computational studies
      suggest carbene stabilization due to the exo-6-silyl group. They also suggest a
      reactant-like transition state for 1,3-hydrogen migration in which the inductive
      effect influences ease of migration. In the case of the exo-6-methoxy group, the
      inductive effect overwhelms any potential resonance-stabilizing effects.

PMID- 11456756
TI  - Proton-transfer reactions between nitroalkanes and hydroxide ion under non-steady
      state conditions. Apparent and real kinetic isotope effects.
AB  - The kinetics of the proton-transfer reactions between 1-nitro-1-(4
      nitrophenyl)ethane (NNPE(H(D))) and hydroxide ion in water/acetonitrile (50/50
      vol %) were studied at temperatures ranging from 289 to 319 K. The equilibrium
      constants for the reactions are large under these conditions, ensuring that the
      back reaction is not significant. The extent of reaction/time profiles during the
      first half-lives are compared with theoretical data for the simple single-step
      mechanism and a 2-step mechanism involving initial donor/acceptor complex
      formation followed by unimolecular proton transfer and dissociation of ions. In
      all cases, the profiles for the reactions of both NNPE(H) and NNPE(D) deviate
      significantly from those expected for the simple single-step mechanism. Excellent
      fits of experimental data with theoretical data for the complex mechanism, in the
      pre-steady-state time period, were observed in all cases. At all base
      concentrations (0.5 to 5.0 mM) and at all temperatures the apparent kinetic
      isotope effects (KIE(app)) were observed to increase with increasing extent of
      reaction. Resolution of the kinetics into microscopic rate constants at 298 K
      resulted in a real kinetic isotope effect (KIE(real)) for the proton-transfer
      step equal to 22. Significant proton tunneling was further indicated by the
      temperature dependence of the rate constants for proton and deuteron transfers:
      KIE(real) ranging from 17 to 26, E(a)(D) -- E(a)(H) equal 2.8 kcal/mol, and
      A(D)/A(H) equal to 4.95.

PMID- 11456757
TI  - Chemoselective elaboration of O-linked glycopeptide mimetics by alkylation of 3
      thioGalNAc.
AB  - A critical branch point in mucin-type oligosaccharides is the beta 1-->3
      glycosidic linkage to the core alpha-N-acetylgalactosamine (GalNAc) residue. We
      report here a strategy for the synthesis of O-linked glycopeptide analogues that
      replaces this linkage with a thioether amenable to construction by chemoselective
      ligation. The key building block was a 2-azido-3-thiogalactose-Thr analogue that
      was incorporated into a peptide by fluorenylmethoxycarbonyl (Fmoc)-based solid
      phase peptide synthesis. Higher order oligosaccharides were readily generated by
      alkylation of the corresponding 3-thioGalNAc with N-bromoacetamido sugars. The
      rapid assembly of "core 1"and "core 3" O-linked glycopeptide mimetics was
      accomplished in this fashion.

PMID- 11456758
TI  - Crystallographic and FTIR spectroscopic evidence of changes in Fe coordination
      upon reduction of the active site of the Fe-only hydrogenase from Desulfovibrio
      desulfuricans.
AB  - Fe-only hydrogenases, as well as their NiFe counterparts, display unusual
      intrinsic high-frequency IR bands that have been assigned to CO and CN(-)
      ligation to iron in their active sites. FTIR experiments performed on the Fe-only
      hydrogenase from Desulfovibrio desulfuricans indicate that upon reduction of the
      active oxidized form, there is a major shift of one of these bands that is
      provoked, most likely, by the change of a CO ligand from a bridging position to a
      terminal one. Indeed, the crystal structure of the reduced active site of this
      enzyme shows that the previously bridging CO is now terminally bound to the iron
      ion that most likely corresponds to the primary hydrogen binding site (Fe2). The
      CO binding change may result from changes in the coordination sphere of Fe2 or
      its reduction. Superposition of this reduced active site with the equivalent
      region of a NiFe hydrogenase shows a remarkable coincidence between the
      coordination of Fe2 and that of the Fe ion in the NiFe cluster. Both
      stereochemical and mechanistic considerations suggest that the small organic
      molecule found at the Fe-only hydrogenase active site and previously modeled as
      1,3-propanedithiolate may, in fact, be di-(thiomethyl)-amine.

PMID- 11456759
TI  - Reaction of [P(2)N(2)]Ta==CH(2)(Me) with ethylene: synthesis of
      [P(2)N(2)]Ta(C(2)H(4))Et, a neutral species with a beta-agostic ethyl group in
      equilibrium with an alpha-agostic ethyl group ([P(2)N(2)] =
      PhP(CH(2)SiMe(2)CH(2))(2)PPh).
AB  - The photolysis of [P(2)N(2)]TaMe(3) ([P(2)N(2)] =
      PhP(CH(2)SiMe(2)NSiMe(2)CH(2))(2)PPh) produces [P(2)N(2)]Ta=CH(2)(Me) as the
      major product. The thermally unstable methylidene complex decomposes in solution
      in the absence of trapping agents to unidentified products. However, in the
      presence of ethylene [P(2)N(2)]Ta=CH(2)(Me) is slowly converted to
      [P(2)N(2)]Ta(C(2)H(4))Et, with [P(2)N(2)]Ta(C(2)H(4))Me observed as a minor
      product. A mechanistic study suggests that the formation of
      [P(2)N(2)]Ta(C(2)H(4))Et results from the trapping of [P(2)N(2)]TaEt, formed by
      the migratory insertion of the methylene moiety into the tantalum-methyl bond.
      The minor product, [P(2)N(2)]Ta(C(2)H(4))Me, forms from the decomposition of a
      tantalacyclobutane resulting from the addition of ethylene to
      [P(2)N(2)]Ta=CH(2)(Me) and is accompanied by the production of an equivalent of
      propylene. Pure [P(2)N(2)]Ta(C(2)H(4))Et can be synthesized by hydrogenation of
      [P(2)N(2)]TaMe(3) in the presence of PMe(3), followed by the reaction of ethylene
      with the resulting trihydride. Crystallographic and NMR data indicate the
      presence of a beta-agostic interaction between the ethyl group and tantalum
      center in [P(2)N(2)]Ta(C(2)H(4))Et. Partially deuterated analogues of
      [P(2)N(2)]Ta(C(2)H(4))Et show a large isotopic perturbation of resonance for both
      the beta-protons and the alpha-protons of the ethyl group, indicative of an
      equilibrium between a beta-agostic and an alpha-agostic interaction for the ethyl
      group in solution. An EXSY spectrum demonstrates that an additional fluxional
      process occurs that exchanges all of the (1)H environments of the ethyl and
      ethylene ligands. The mechanism of this exchange is believed to involve the
      direct transfer of the beta-agostic hydrogen atom from the ethyl group to the
      ethylene ligand, via the so-called beta-hydrogen transfer process.

PMID- 11456760
TI  - Engineering of efficient panchromatic sensitizers for nanocrystalline TiO(2)
      based solar cells.
AB  - A new series of panchromatic ruthenium(II) sensitizers derived from carboxylated
      terpyridyl complexes of tris-thiocyanato Ru(II) have been developed. Black dye
      containing different degrees of protonation
      [(C(2)H(5))(3)NH][Ru(H(3)tcterpy)(NCS)(3)] 1,
      [(C(4)H(9))(4)N](2)[Ru(H(2)tcterpy)(NCS)(3)] 2,
      [(C(4)H(9))(4)N](3)[Ru(Htcterpy)(NCS)(3)] 3, and
      [(C(4)H(9))(4)N](4)[Ru(tcterpy)(NCS)(3)] 4 (tcterpy = 4,4',4' '-tricarboxy
      2,2':6',2' '-terpyridine) have been synthesized and fully characterized by UV
      vis, emission, IR, Raman, NMR, cyclic voltammetry, and X-ray diffraction studies.
      The crystal structure of complex 2 confirms the presence of a Ru(II)N6 central
      core derived from the terpyridine ligand and three N-bonded thiocyanates.
      Intermolecular H-bonding between carboxylates on neighboring terpyridines gives
      rise to 2-D H-bonded arrays. The absorption and emission maxima of the black dye
      show a bathochromic shift with decreasing pH and exhibit pH-dependent excited
      state lifetimes. The red-shift of the emission maxima is due to better pi
      acceptor properties of the acid form that lowers the energy of the CT excited
      state. The low-energy metal-to-ligand charge-transfer absorption band showed
      marked solvatochromism due to the presence of thiocyanate ligands. The
      Ru(II)/(III) oxidation potential of the black dye and the ligand-based reduction
      potential shifted cathodically with decreasing number of protons and showed more
      reversible character. The adsorption of complex 3 from methoxyacetonitrile
      solution onto transparent TiO(2) films was interpreted by a Langmuir isotherm
      yielding an adsorption equilibrium constant, K(ads), of (1.0 +/- 0.3) x 10(5) M(
      1). The amount of dye adsorbed at monolayer saturation was (n(alpha) = 6.9 +/-
      0.3) x 10(-)(8) mol/mg of TiO(2), which is around 30% less than that of the cis
      di(thiocyanato)bis(2,2'-bipyridyl-4,4'-dicarboxylate)ruthenium(II) complex. The
      black dye, when anchored to nanocrystalline TiO(2) films achieves very efficient
      sensitization over the whole visible range extending into the near-IR region up
      to 920 nm, yielding over 80% incident photon-to-current efficiencies (IPCE).
      Solar cells containing the black dye were subjected to analysis by a photovoltaic
      calibration laboratory (NREL, U.S.A.) to determine their solar-to-electric
      conversion efficiency under standard AM 1.5 sunlight. A short circuit
      photocurrent density obtained was 20.5 mA/cm(2), and the open circuit voltage was
      0.72 V corresponding to an overall conversion efficiency of 10.4%.

PMID- 11456761
TI  - A homogeneous catalyst for selective O(2) oxidation at ambient temperature.
      diversity-based discovery and mechanistic investigation of thioether oxidation by
      the Au(III)Cl(2)NO(3)(thioether)/O(2) system.
AB  - A library of inorganic complexes with reversible redox chemistry and/or the
      ability to catalyze homogeneous oxidations by peroxides, including but not
      limited to combinations of polyoxometalate anions and redox-active cations, was
      constructed. Evaluation of library members for the ability to catalyze aerobic
      sulfoxidation (O(2) oxidation of the thioether, 2-chloroethyl ethyl sulfide,
      CEES) led to the discovery that a combination of HAuCl(4) and AgNO(3) forms a
      catalyst that is orders of magnitude faster than the previously most reactive
      such catalysts (Ru(II) and Ce(IV) complexes) and one effective at ambient
      temperature and 1 atm air or O(2). If no O(2) but high concentrations of
      thioether are present, the catalyst is inactivated by an irreversible formation
      of colloidal Au(0). However, this inactivation is minimal in the presence of
      O(2). The stoichiometry is R(2)S + (1)/(2)O(2) --> R(2)S(O), a 100% atom
      efficient oxygenation, and not oxidative dehydrogenation. However, isotope
      labeling studies with H(2)(18)O indicate that H(2)O and not O(2) or H(2)O(2) is
      the source of oxygen in the sulfoxide product; H(2)O is consumed and subsequently
      regenerated in the mechanism. The rate law evaluated for every species present in
      solution, including the products, and other kinetics data, indicate that the
      dominant active catalyst is Au(III)Cl(2)NO(3)(thioether) (1); the rate-limiting
      step involves oxidation of the substrate thioether (CEES) by Au(III); reoxidation
      of the resulting Au(I) to Au(III) by O(2) is a fast subsequent step. The rate of
      sulfoxidation as Cl is replaced by Br, the solvent kinetic isotope effect
      (k(H)(2)(O)/k(D)(2)(O) = 1.0), and multiparameter fitting of the kinetic data
      establish that the mechanism of the rate-limiting step involves a bimolecular
      attack of CEES on a Au(III)-bound halide and it does not involve H(2)O. The
      reaction is mildly inhibited by H(2)O and the CEESO product because these
      molecules compete with those needed for turnover (Cl(-), NO(3)(-)) as ligands for
      the active Au(III). Kinetic studies using DMSO as a model for CEESO enabled
      inhibition by CEESO to be assessed.

PMID- 11456762
TI  - Reactions of VX, GB, GD, and HD with nanosize Al(2)O(3). Formation of
      aluminophosphonates.
AB  - Room-temperature reactions of VX, GB, GD, and HD with nanosize Al(2)O(3) (AP
      Al(2)O(3)) have been characterized by (31)P, (13)C, and (27)Al MAS NMR. Nerve
      agents VX, GB, and GD hydrolyze to yield surface-bound complexes of their
      corresponding nontoxic phosphonates. At sufficiently high loadings, discreet
      aluminophosphonate complexes, Al[OP(O)(CH(3))OR](3), are generated which are
      identical to synthesized model compounds. Thus the reaction with phosphonic acids
      is not just surface-limited, but can continue to the core of alumina particles.
      HD mainly hydrolyzes at lower loadings to yield thiodiglycol (TG, 71%) and a
      minor amount of the CH-TG sulfonium ion (12%), although some elimination of HCl
      is also observed (17%). The reactive capacity for HD is evidently exceeded at
      high loadings, where complete conversion to TG is hindered. However, addition of
      excess water results in the quantitative hydrolysis of sorbed HD to CH-TG. On AP
      Al(2)O(3) dried to remove physisorbed water, (13)C CP-MAS NMR detects a surface
      alkoxide consistent with that of TG.

PMID- 11456763
TI  - Composition dependence of the nucleation energy of iron antimonides from
      modulated elemental reactants.
AB  - Modulated elemental reactants containing iron and antimony were found to react at
      low temperature (T < 200 degrees C) forming either FeSb(2) or FeSb(3) depending
      on both the layer thicknesses and the overall composition of the initial
      reactant. For films containing 75% antimony and 25% iron, the metastable compound
      FeSb(3) was observed to nucleate and grow if the layer thickness was below
      approximately 35 A. Above this critical thickness for the modulation, annealing
      led to the formation of FeSb(2). This, combined with low-angle diffraction data,
      suggests that the initial interdiffusion between iron and antimony layers in an
      elementally modulated reactant results in the formation of an amorphous reaction
      intermediate if the layering thickness is less than 35 A. For modulated reactants
      with composition between 70 and 90 atomic % antimony and below this critical
      layer thickness, the metastable compound FeSb(3) formed. In more iron-rich
      modulated reactants FeSb(2) nucleates. The nucleation temperature and the
      nucleation energy of FeSb(3) were found to be a function of the composition of
      the amorphous intermediate, while those of FeSb(2) were found to be relatively
      independent of composition.

PMID- 11456764
TI  - Synthesis of ordered and disordered silicas with uniform pores on the border
      between micropore and mesopore regions using short double-chain surfactants.
AB  - Silica molecular sieves with uniform pores on the borderline between micropore
      (diameter <2 nm) and mesopore (from 2 to 50 nm) ranges were synthesized by a
      novel method using judiciously chosen mixtures of short double-chain
      alkylammonium surfactants. These silicas were characterized using X-ray
      diffraction (XRD), thermogravimetry, and nitrogen and argon adsorption. The
      calcined materials exhibited either 2-dimensional (2-D) hexagonal or disordered
      structures with XRD interplanar spacing from 2.51 to 2.93 nm, including the value
      of as small as 2.69 nm for highly ordered 2-D hexagonal silica. The dependence of
      the pore size and surfactant content on the surfactant chain length provided
      strong evidence for supramolecular templating being operative in the formation of
      small-pore silicas, even for the surfactant chain length of six carbon atoms.
      Both hexagonally ordered and disordered calcined samples were shown to exhibit
      narrow pore size distributions with maxima in the range from 1.96 to 2.61 nm
      (reliably evaluated on the basis of the unit-cell dimension and pore volume for 2
      D hexagonal materials, and calculated using a properly calibrated procedure),
      tailored by the surfactant chain length. The samples exhibited primary pore
      volumes from 0.28 to 0.54 cm(3) g(-1) and specific surface areas from 730 to 930
      m(2) g(-1). Because of their small yet uniform pore size and large specific
      surface area, the silicas reported herein promise to be useful in applications in
      adsorption and catalysis. Adsorption studies of these materials provided a unique
      new insight into the pore-filling mechanism for small-pore materials. Moreover,
      the approach proposed herein is expected to facilitate the synthesis of not only
      small-pore silicas but also materials with other framework compositions, thus
      largely contributing to bridging the gap in attainable pore sizes between
      micropore and mesopore ranges.

PMID- 11456765
TI  - Hydrogenolysis of cyclohexane over Ir/SiO(2) catalyst: a mechanistic study of
      carbon--carbon bond cleavage on metallic surfaces.
AB  - The hydrogenolysis of cyclohexane catalyzed by supported Ir/SiO(2) has been
      studied to get mechanistic information on the elementary steps of C--C bond
      cleavage for cyclic saturated hydrocarbons. The reaction was studied under
      conditions in which no dehydrogenation to benzene occurs. When a mixture of
      cyclohexane and H(2) flows over a Ir/SiO(2) catalyst at 200 degrees C and for a
      H(2)/cyclohexane ratio superior to 40, methane, ethane, propane, n-butane, n
      pentane, and n-hexane are identified to be primary products. The hydrogenolysis
      of ethane and n-hexane has also been studied to clarify several mechanistic
      questions. To account for the primary products in the above reactions, a
      mechanism is proposed in which the key step of the carbon--carbon bond cleavage
      occurs via concerted electronic transfer in dimetallacyclopentane intermediate.
      The comparison of product distributions in the hydrogenolysis of cyclohexane and
      that observed for n-hexane led to conclusions about the relative ease of carbon-
      carbon bond cleavage with respect to surface alkyl isomerization.

PMID- 11456766
TI  - Understanding the mechanism of B(12)-dependent diol dehydratase: a synergistic
      retro-push--pull proposal.
AB  - Ab initio molecular orbital theory is used to investigate the coenzyme B(12)
      dependent reactions catalyzed by diol dehydratase. The key step in such reactions
      is believed to be a 1,2-hydroxyl migration, which occurs within free-radical
      intermediates. The barrier for this migration, if unassisted, is calculated to be
      too high to be consistent with the observed reaction rate. However, we find that
      "pushing" the migrating hydroxyl, through interaction with a suitable acid, is
      able to provide significant catalysis. This is denoted retro-push catalysis, the
      retro prefix signifying that the motion of the migrating group is in the
      direction opposite to the electron motion. Similarly, the "pulling" of the
      migrating group, through interaction of the spectator hydroxyl with an
      appropriate base, is found to substantially reduce the rearrangement barrier.
      Importantly, the combination of these two effects results in a barrier reduction
      that is notably greater than additive. This synergistic interplay of the push and
      the pull provides an attractive means of catalysis. Our proposed retro-push--pull
      mechanism leads to results that are consistent with isotope-labeling experiments,
      with experimental rate data, and with the crystal structure of the enzyme.

PMID- 11456767
TI  - A mechanistic study of reactions of stable disilenes with haloalkanes.
AB  - Mechanisms of the reactions of three tetrakis(trialkylsilyl)disilenes and a
      tetraaryldisilene with various haloalkanes such as carbon tetrachloride,
      chloroform, dichloromethane, which gave the corresponding 1-alkyl-2
      chlorodisilanes and/or 1,2-dichlorodisilanes, were investigated in detail. As
      evidenced by an ESR observation of an intermediate radical, these reactions were
      quite unusual, forming neutral radical pairs from two closed shell molecules at
      the first step; no similar reactions have been observed between alkenes and
      haloalkanes. Low oxidation potentials of these disilenes, large negative
      activation entropies, and solvent effects for the rates are in good accord with
      the direct halogen abstraction of disilenes from haloalkanes instead of single
      electron transfer at the rate-determining first step. The structure--reactivity
      relationship of the reactions and the Hammond postulate suggest that the
      transition state structures for the first step are similar to those for the
      halogen abstraction by silyl radicals, but more product-like.

PMID- 11456768
TI  - Energy analysis of metal-ligand bonding in transition metal complexes with
      terminal group-13 diyl ligands (CO)(4)Fe-ER, Fe(EMe)(5) and Ni(EMe)(4) (E = B-Tl;
      R = Cp, N(SiH(3))(2), Ph, Me) reveals significant pi bonding in homoleptical
      molecules.
AB  - The metal-ligand bonds of the title compounds have been investigated with the
      help of an energy partitioning analysis at the DFT level. It was found that the
      attractive orbital interactions between Fe and ER in (CO)(4)Fe-ER arise mainly
      from Fe <-- ER sigma donation. Only the boron diyl complexes (CO)(4)Fe-BR have
      significant contributions by Fe --> ER pi back-donation, but the Fe <-- BR sigma
      donation remains the dominant orbital interaction term. The relative
      contributions of Fe-ER sigma donation and pi back-donation are only slightly
      altered when R changes from a good pi donor to a poor pi donor. Electrostatic
      forces between the metal fragment and the diyl ligand are always attractive, and
      they are very strong. They arise from the attraction between the local negative
      charge concentration at the overall positively charged donor atom E of the Lewis
      base ER and the positive charge of the iron nucleus. Electrostatic interactions
      and covalent interactions in (CO)(4)Fe-ER complexes have a similar strength when
      E is Al--Tl and when R is a good pi donor substituent. The Fe-BR bonds of the
      boron carbonyldiyl complexes have a significantly higher ionic character than the
      heavier group-13 analogues. Weak pi donor substituents R enhance the ionic
      character of the (CO)(4)Fe-ER bond. The metal-ligand bonds in the homoleptic
      complexes Fe(EMe)(5) and Ni(EMe)(4) have a higher ionic character than in
      (CO)(4)Fe-ER. The contribution of the TM --> ER pi back-donation to the Delta
      E(orb) term becomes clearly higher and contributes significantly to the total
      orbital interactions in the homoleptic complexes where no other pi acceptor
      ligands are present. The ligand BMe is nearly as strong a pi acceptor in
      Fe(BMe)(5) as CO is in Fe(CO)(5).

PMID- 11456769
TI  - In situ X-ray diffraction and solid-state NMR study of the fluorination of gamma
      Al(2)O(3) with HCF(2)Cl.
AB  - In situ X-ray diffraction (XRD) and NMR methods were used to follow the
      structural changes that occur during the dismutation reaction of
      hydrochlorofluorocarbon-22 (CHClF(2)) over gamma-alumina. Use of a flow cell
      allowed diffraction patterns to be recorded, while the reaction products were
      simultaneously monitored downstream of the catalyst bed, by gas chromatography.
      No visible structural changes of gamma-Al(2)O(3) were observed at 300 degrees C,
      the temperature at which this material becomes active for catalysis. A new phase
      began to form at 360 degrees C, which by 500 degrees C completely dominated the
      XRD powder pattern. (19)F/(27)Al cross-polarization (CP) experiments of gamma
      Al(2)O(3) activated at 300 degrees C showed that AlF(3) had already begun to form
      at this temperature. By 400 degrees C, resonances from a phase that resembles
      alpha-AlF(3) dominate both the (19)F and (27)Al NMR spectra of the used catalyst.
      In situ XRD experiments of the catalytically inactive alpha-AlF(3) phase were
      performed to investigate the structural changes of this material, associated with
      the extent of tilting of the AlF(6) octahedra in this ReO(3)-related structure,
      as a function of temperature. Structural refinements of this sample, and the
      catalytically active phase that grows over gamma-Al(2)O(3), demonstrate that the
      catalyst is structurally similar to the rhombohedral form of alpha-AlF(3).
      Differences between the two phases are ascribed to defects in the catalyst, which
      limit the flexibility of the structure; these may also be responsible for the
      differences in the catalytic behavior of the two materials.

PMID- 11456770
TI  - Density functional studies on the Pauson--Khand reaction.
AB  - The Pauson--Khand reaction represents a one-step Co(2)(CO)(8)-catalyzed synthesis
      of cyclopentenone through [2 + 2 + 1] assembly of one molecule each of alkene,
      alkyne, and carbon monoxide. Density functional studies (B3LYP/631LAN) on the
      reaction pathway of the Pauson--Khand (PK) reaction reported here for the first
      time provides valuable information on the structures and energetics of various
      intermediates and transition states. The PK reaction consists of olefin
      insertion, CO insertion, and reductive elimination steps. The olefin insertion
      step was found to be an irreversible step that determines the stereo- and
      regiochemistry of the overall reaction. The following steps are low activation
      energy processes and reversible. The bond-forming events occur only on one of the
      two metal atoms, while the second metal atom not only acts as an anchor that
      fixes the metal cluster to the organic substrate but also exerts electronic
      influences on the reaction at the first atom.

PMID- 11456771
TI  - A hybrid potential reaction path and free energy study of the chorismate mutase
      reaction.
AB  - We present a combination of two techniques--QM/MM statistical simulation methods
      and QM/MM internal energy minimizations--to get a deeper insight into the
      reaction catalyzed by the enzyme chorismate mutase. Structures, internal energies
      and free energies, taken from the paths of the reaction in solution and in the
      enzyme have been analyzed in order to estimate the relative importance of the
      reorganization and preorganization effects. The results we obtain for this
      reaction are in good agreement with experiment and show that chorismate mutase
      achieves its catalytic efficiency in two ways; first, it preferentially binds the
      active conformer of the substrate and, second, it reduces the free energy of
      activation for the reaction relative to that in solution by providing an
      environment which stabilizes the transition state.

PMID- 11456772
TI  - Investigation of the polymorphs of dimethyl-3,6-dichloro-2,5
      dihydroxyterephthalate by (13)C solid-state NMR spectroscopy.
AB  - Two of the three conformational polymorphs of dimethyl-3,6-dichloro-2,5
      dihydroxyterephthalate are studied by solid-state NMR techniques. The structural
      differences between the polymorphs have previously been studied by X-ray. In
      these two polymorphs named white and yellow due to their color, the major
      structural difference is the torsional angle between the ester group and the
      aromatic ring. The yellow form has a dihedral angle of 4 degrees between the
      plane of the aromatic ring and the plane of the ester group, while the white form
      has two different molecules per unit cell with dihedral angles of 70 degrees and
      85 degrees. This change greatly affects the conjugation in the pi-electronic
      system. In addition, there are differences in the hydrogen-bonding patterns, with
      the white form having intermolecular hydrogen bonds and the yellow form having
      intramolecular hydrogen bonds. In this work, the carbon isotropic chemical shift
      values and the chlorine electric field gradient (EFG) tensor information are
      extracted from the (13)C MAS spectra, and the principal values of the chemical
      shift tensors of the carbons are obtained from 2D FIREMAT experiments. Quantum
      chemical calculations of the chemical shift tensor data as well as the EFG tensor
      are performed at the HF and DFT levels of theory on individual molecules and on
      stacks of three molecules to account for the important intermolecular
      interactions in the white form. The differences between the spectral data on the
      two polymorphs are discussed in terms of the known electronic and structural
      differences.

PMID- 11456773
TI  - Substituent effects on the oxidation and reduction potentials of phenylthiyl
      radicals in acetonitrile.
AB  - Oxidation (E(1/2)(ox)) and reduction potentials (E(1/2)(red)) of a series of para
      substituted phenylthiyl radicals XC(6)H(4)S* generated from the pertinent
      disulfides or thiophenols have been measured by means of photomodulated
      voltammetry in acetonitrile. The values of E(1/2)(ox) are of particular interest
      as they give access to the hitherto unknown thermochemistry of short-lived
      phenylsulfenium cations in solution. Both E(1/2)(OX) and E(1/2)(red) decrease as
      the electron-donating power of the substituent raises, resulting in linear
      correlations with the Hammett substituent coefficient sigma(+) with slopes rho(+)
      of 4.7 and 6.4, respectively. The finding of a larger substituent effect on than
      is a consequence of a corresponding development in the electron affinities and
      ionization potentials of XC(6)H(4)S* as revealed by quantum-chemical
      calculations. Solvation energies extracted for XC(6)H(4)S(+) and XC(6)H(4)S(-)
      from thermochemical cycles show the expected substituent dependency; i.e., the
      absolute values of the solvation energies decrease as the charge becomes more
      delocalized in the ions. Acetonitrile is better in solvating XC(6)H(4)S(+) than
      XC(6)H(4)S(-) for most substituents, even if there is a substantial
      delocalization of the charge in the series of phenylsulfenium cations. The
      substituent effect on is smaller in aqueous solution than acetonitrile, which is
      attributed to the ability of water to stabilize in particular localized anions
      through hydrogen bonding.

PMID- 11456774
TI  - Structural studies of an oligodeoxynucleotide containing a trimethylene
      interstrand cross-link in a 5'-(CpG) motif: model of a malondialdehyde cross
      link.
AB  - Malondialdehyde (MDA), a known mutagen and suspected carcinogen, is a product of
      lipid peroxidation and byproduct of eicosanoid biosynthesis. MDA can react with
      DNA to generate potentially mutagenic adducts on adenine, cytosine, and
      particularly guanine. In addition, repair-dependent frame shift mutations in a
      GCGCGC region of Salmonella typhimurium hisD3052 have been attributed to
      formation of interstrand cross-links (Mukai, F. H. and Goldstein, B. D. Science
      1976, 191, 868--869). The cross-linked species is unstable and has never been
      characterized but has been postulated to be a bis-imino linkage between N(2)
      positions of guanines. An analogous linkage has now been investigated as a stable
      surrogate using the self-complementary oligodeoxynucleotide sequence 5'
      d(AGGCG*CCT)(2,) in which G* represents guanines linked via a trimethylene chain
      between N(2) positions. The solution structure, obtained by NMR spectroscopy and
      molecular dynamics using a simulated annealing protocol, revealed the cross-link
      only minimally distorts duplex structure in the region of the cross-link. The
      tether is accommodated by partially unwinding the duplex at the lesion site to
      produce a bulge and tipping the guanine residues; the two guanines and the tether
      attain a nearly planar conformation. This distortion did not result in
      significant bending of the DNA, a result which was confirmed by gel
      electrophoresis studies of multimers of a 21-mer duplex containing the cross
      link.

PMID- 11456775
TI  - Split--pool synthesis of 1,3-dioxanes leading to arrayed stock solutions of
      single compounds sufficient for multiple phenotypic and protein-binding assays.
AB  - Diversity-oriented organic synthesis offers the promise of advancing chemical
      genetics, where small molecules are used to explore biology. While the split-
      pool synthetic method is theoretically the most effective approach for the
      production of large collections of small molecules, it has not been widely
      adopted due to numerous technical and analytical hurdles. We have developed a
      split--pool synthesis leading to an array of stock solutions of single 1,3
      dioxanes. The quantities of compounds are sufficient for hundreds of phenotypic
      and protein-binding assays. The average concentration of these stock solutions
      derived from a single synthesis bead was determined to be 5.4 mM in 5 microL of
      DMSO. A mass spectrometric strategy to identify the structure of molecules from a
      split--pool synthesis was shown to be highly accurate. Individual members of the
      1,3-dioxane library have activity in a variety of phenotypic and protein-binding
      assays. The procedure developed in this study allows many assays to be performed
      with compounds derived from individual synthesis beads. The synthetic compounds
      identified in these assays should serve as useful probes of cellular and
      organismal processes.

PMID- 11456776
TI  - Supramolecular polar thin films built by surfactant liquid crystals: polarization
      tunable multilayer self-assemblies with in-plane ferroelectric ordering of ion
      based dipoles.
AB  - Polar order in the phosphonium liquid crystal thin films, which are composed of
      two-dimensional ion-pair-based domains separated by the insulating hydrocarbon
      layers, was probed by second harmonic generation (SHG) analysis. Despite the
      ordinary amphiphilic self-assemblies containing no pi-electron moieties, the
      solid-state thin films retaining a smectic layer structure showed clearly an SHG
      activity, while the disordered films without the layer structure were not active
      at all for the SHG. It was found that the multilayer structure plays a crucial
      role for the SHG from the phosphonium thin films and the ionic layers act as an
      SHG-active site. The most significant characteristic of this system is to possess
      an ability to control SHG intensity electrically. The efficiency of the SHG
      process in the thin-film assemblies was enhanced by applying an external electric
      field parallel to the layer plane. Furthermore, through evaluation of thermal
      stability of the sample films, it was revealed that the SHG signals were detected
      only in the solid-state temperature range and the disappearance of the SHG occurs
      earlier than the solid-to-liquid crystalline phase transition. These results
      demonstrated that the origin of polar order in the phosphonium thin films is due
      to in-plane noncentrosymmetric arrangement (ferroelectric ordering) of ion pairs
      as an electric dipole, that is, dipole symmetry in an ionic layer.

PMID- 11456777
TI  - Quantum mechanical designs toward planar delocalized cyclooctatetraene: a new
      target for synthesis.
AB  - Ab initio and hybrid density functional quantum mechanical computation are
      applied to the structure and energetics of a series of annelated
      cyclooctatetraenes. Tetrakis-cyclobuteno, perfluorocyclobuteno or
      bicyclo[2.1.1]hexeno annelations result in planar structures with distinct exo
      and endo valence tautomers of the double bonded cycle. The contribution of each
      basic annelation to the exo/endo relative energy is estimated. An additivity
      scheme for approximating the energy of a mixed system is developed and compared
      to the quantum mechanical prediction. Bis bicyclic annelation to the a and d
      positions creates "valence tautomeric frustration" and strongly perturbs the
      molecular structure. This phenomenon leads to a general design for a planar
      cyclooctatetraenes where the "delocalized" diradicaloid state is the minimum
      energy form. These compounds are seen as excellent targets for chemical
      synthesis.

PMID- 11456778
TI  - Reactivities of inositol and ribonucleoside phosphodiesters toward P--O bond
      cleavage.

PMID- 11456779
TI  - A novel type of carbon--carbon double bond cleavage of 1,1-disubstituted alkenes
      on a triruthenium polyhydrido cluster.

PMID- 11456780
TI  - Supramolecular holoenzymes: activity modulation of endonuclease by the use of
      synthetic bilayer membranes as regulatory cofactors.

PMID- 11456781
TI  - Enthalpy--entropy compensation in a photocycle: the K-to-L transition in sensory
      rhodopsin II from Natronobacterium pharaonis.

PMID- 11456782
TI  - Efficient synthesis of benzene and planar cyclooctatetraene fully annelated with
      bicyclo[2.1.1]hex-2-ene.

PMID- 11456783
TI  - Residual dipolar (1)H-(1)H couplings of methyl groups in weakly aligned proteins.

PMID- 11456784
TI  - Metal ion-directed cooperative triple helix formation of glutamic acid-
      oligonucleotide conjugate.

PMID- 11456785
TI  - High-temperature protein mass mapping using a thermophilic protease.

PMID- 11456786
TI  - A DNA polymerase with specificity for five base pairs.

PMID- 11456787
TI  - Stoichiometric, catalytic, and enantioface-selective hydrogenation of C==N bonds
      by an ionic mechanism.

PMID- 11456788
TI  - Xenon difluoride exchanges fluoride under mild conditions: a simple preparation
      of [(18)F]xenon difluoride for PET and mechanistic studies.

PMID- 11456789
TI  - Metal chelators inhibit S-nitrosation of Cys beta 93 in oxyhemoglobin.

PMID- 11456790
TI  - Photoregulation of fluorescence in a porphyrinic dithienylethene photochrome.

PMID- 11456791
TI  - Acetyl coenzyme A synthesis from unnatural methylated corrinoids: requirement for
      "base-off" coordination at cobalt.

PMID- 11456792
TI  - N,N'-dimethylpiperazinium-2,3-dithione triiodide,[Me(2)Pipdt]I(3), as a powerful
      new oxidation agent toward metallic platinum. Synthesis and X-ray structures of
      the reagent and the product [Pt(Me(2)Pipdt)(2)](I(3))(2).

PMID- 11456793
TI  - Electrophoretic characterization of dynamic biochemical microenvironments.

PMID- 11456794
TI  - Chain length-dependent affinity of helical foldamers for a rodlike guest.

PMID- 11456795
TI  - X-ray crystal structure of alcohol products bound at the active site of soluble
      methane monooxygenase hydroxylase.

PMID- 11456796
TI  - A de novo designed peptide ligase: a mechanistic investigation.
AB  - A 33-residue de novo designed peptide ligase is reported which catalyzes the
      template-directed condensation of suitably activated short peptides with
      catalytic efficiencies in excess of 10(5) ([k(cat)/K(m)]/k(uncat)). The ligase
      peptide, derived from natural and designed alpha-helical coiled-coil proteins,
      presents a surface for substrate assembly via formation of a hydrophobic core at
      the peptide interface. Charged residues flanking the core provide additional
      binding specificity through electrostatic complementarity. Addition of the
      template to an equimolar fragment solution results in up to 4100-fold increases
      in initial reaction rates. Dramatic decreases in efficiency upon mutation of
      charged residues or increase in ionic strength establishes the importance of
      electrostatic recognition to ligase efficiency. Although most of the increase in
      reaction efficiency is due to entropic gain from binding of substrates in close
      proximity, mechanistic studies with altered substrates demonstrate that the
      system is highly sensitive to precise ordering at the point of ligation. Taken
      together these results represent the first example of a peptide catalyst with
      designed substrate binding sites which can significantly accelerate a bimolecular
      reaction and support the general viability of alpha-helical protein assemblies in
      artificial enzyme design.

PMID- 11456797
TI  - New manzamine alkaloids with potent activity against infectious diseases.
AB  - The isolation of the new enantiomers of 8-hydroxymanzamine A (1), manzamine F
      (2), along with the unprecedented manzamine dimer, neo-kauluamine from an
      undescribed genus of Indo-Pacific sponge (family Petrosiidae, order
      Haplosclerida) is reported. The relative stereochemistry of neo-kauluamine was
      established through detailed analysis of NOE-correlations combined with molecular
      modeling. The significance of the manzamines as in vivo antimalarial agents with
      superior activity to the clinically used drugs artemisinin and chloroquine is
      discussed along with the activity in vitro against the AIDS-opportunistic
      infectious diseases tuberculosis and toxoplasmosis. Reexamination of the sponges
      identified as Prianos, and Pachypellina, in earlier publications has confirmed
      that these are members of the same genus as the sponge described here, but differ
      at the species level.

PMID- 11456798
TI  - Synthesis of N,N'-bis(acrylamido)acetic acid-based T-antigen glycodendrimers and
      their mouse monoclonal IgG antibody binding properties.
AB  - Novel glycodendrimers based on N,N'-bis(acrylamido)acetic acid core with
      valencies between two and six were synthesized. The breast cancer-associated T
      antigen carbohydrate marker, (beta-Gal-(1-3)-alpha-GalNAc-OR), was then
      conjugated by (i) 1,4-conjugate addition of thiolated T-antigen to the N
      acrylamido dendritic cores and by (ii) amide bond formation between an acid
      derivative of the T-antigen and the polyamino dendrimers. The protein-binding
      ability of these new glycodendrimers was fully demonstrated by turbidimetric
      analysis and by enzyme-linked immunosorbent assay (ELISA) using peanut lectin
      from Arachis hypogaea and a mouse monoclonal antibody (MAb) FAA-J11 (IgG3). When
      tested as inhibitors of binding between MAb and a polymeric form of the T-antigen
      (T-antigen-co-polyacrylamide) used as a coating antigen, di- (17), tetra- (20),
      hexa- (21), and tetravalent (22) dendrimers showed IC(50) values of 174, 19, 48,
      and 18 nM, respectively. Two tetramers showed 120- to approximately 128-fold
      increased inhibitory properties over the monovalent antigen 6 used as a standard
      (IC(50) 2.3 mM). Heterobifunctional glycodendrimer bearing a biotin probe was
      also prepared for cancer cell labeling.

PMID- 11456799
TI  - Diastereoselective tandem 6-exo carbolithiation intramolecular ring opening in (
      )-8-aminomenthol-derived perhydrobenzoxazines. A new synthesis of enantiopure 4
      substituted tetrahydro isoquinolines and 2-azabenzonorbornanes.
AB  - Aryllithiums prepared by bromine-lithium interchange in chiral 2-(o-bromophenyl)
      substituted perhydro-1,3-benzoxazines participate in the intramolecular 6-exo
      carbolithiation reaction with unactivated double bonds attached to the nitrogen
      substituent of the heterocycle. When the reaction time is extended or no TMEDA is
      used, the cyclized lithium intermediates react intramolecularly with the N,O
      acetal system leading to 2-azabenzonorbornane derivatives. The reactions are
      highly stereoselective and constitute a high-yielding synthesis of enantiopure 4
      substituted tetrahydroisoquinolines or 7-substituted 2-azabenzonorbornanes.

PMID- 11456800
TI  - Stereospecificity of acetylene reduction catalyzed by nitrogenase.
AB  - In addition to catalyzing the reduction of dinitrogen to ammonia, the
      metalloenzyme nitrogenase catalyzes the reduction of a number of alternative
      substrates, including acetylene (C(2)H(2)) to ethylene (C(2)H(4)) and, in certain
      cases, to ethane (C(2)H(6)). The stereochemistry of proton addition for C(2)D(2)
      reduction to C(2)D(2)H(2) catalyzed by the Mo-dependent nitrogenase has been used
      to probe substrate binding and proton addition mechanisms. In the present work,
      the C(2)D(2) reduction stereospecificity of altered MoFe proteins having amino
      acid substitutions within the active site FeMo-cofactor environment was examined
      by Fourier transform infrared (FTIR) spectroscopy. Altered MoFe proteins examined
      included those having the alpha-subunit 96(Arg) residue substituted by Gln, Leu,
      or Ala, the alpha-subunit 69(Gly) residue substituted by Ser, and the alpha
      subunit 195(His) residue substituted by Asn. The stereochemistry of proton
      addition to C(2)D(2) does not correlate with the measured K(m) values for
      C(2)H(2) reduction, or with the ability of the enzyme to reduce C(2)H(2) by four
      electrons to yield C(2)H(6). Instead, the electron flux through nitrogenase was
      observed to significantly influence the ratio of cis- to trans-1,2-C(2)H(2)D(2)
      formed. Finally, the product distribution observed for reduction of C(2)H(2) in
      D(2)O is not consistent with an earlier proposed enzyme-bound intermediate. An
      alternative model that accounts for the stereochemistry of C(2)H(2) reduction by
      nitrogenase based on a branched reaction pathway and an enzyme-bound eta(2)-vinyl
      intermediate is proposed.

PMID- 11456801
TI  - Oligonucleotide-directed assembly of materials: defined oligomers.
AB  - A nano-architectural system that has high variability while maintaining component
      specificity is described. Tetraphenylcyclobutadiene(cyclopentadienyl)cobalt
      complexes and phenyleneethynylene trimers were synthesized and subsequently
      modified with oligonucleotides utilizing standard phosphoramidite chemistry. The
      resulting oligonucleotide modified organics (OMOs) were characterized by UV-vis
      spectroscopy, fluorescence spectroscopy, and phosphate analysis. Hybridization of
      these OMOs resulted in a series of self-assembled oligomeric hybrids of varying
      length and topology. These hybrids were characterized by melting temperature,
      polyacrylamide gel electrophoresis, and fluorescence spectroscopy. This model
      system demonstrates the power of DNA to self-assemble modules of interest
      independent of the module itself.

PMID- 11456802
TI  - Disappearing and reappearing polymorphs. The benzocaine:picric acid system.
AB  - The low-melting polymorphic modification of the 1:1 complex of benzocaine (BC)
      and picric acid (PA) had earlier been reported to be an example of a
      "disappearing polymorph". The BC:PA system has been reinvestigated by
      thermomicroscopy, calorimetry, solid-state NMR, and X-ray crystallography. The
      phase diagram has been derived, and robust procedures for the crystallization of
      the two 1:1 complexes, a hydrate of the 1:1 complex, and a 2:1 complex have been
      devised. The structures of all four phases have been determined and compared
      using graph set analysis to characterize the hydrogen-bonding patterns. It is
      shown that the thorough microscopic investigation of the thermal behavior,
      combined with calorimetric methods, can lead to the development of strategies to
      crystallize metastable polymorphic forms which may be difficult to obtain once
      their stable congeners have been obtained.

PMID- 11456803
TI  - Halogenation of cubane under phase-transfer conditions: single and double C-H
      bond substitution with conservation of the cage structure.
AB  - The first highly selective C-H chlorination, bromination, and iodination of
      cubane (1) utilizing polyhalomethanes as halogen sources under phase-transfer
      (PT) conditions is described. Isomeric dihalocubanes with all possible
      combinations of chlorine, bromine, and iodine in ortho, meta, and para positions
      were also prepared by this method; m-dihalo products form preferentially. Ab
      initio and density functional theory (DFT) computations were used to rationalize
      the pronounced differences in the reactions of 1 with halogen (Hal(*)) vs carbon
      centered trihalomethyl (Hal(3)C(*)) radicals (Hal = Cl, Br). For Hal(3)C radicals
      the C-H abstraction pathway is less unfavorable (DeltaG(double dagger)(298) =
      21.6 kcal/mol for Cl(3)C(*) and 19.4 kcal/mol for Br(3)C(*) at B3LYP/6
      311+G//B3LYP/6-31G) than the fragmentation of the cubane skeleton via S(H)2
      attack on one of the carbon atoms of 1 (DeltaG(double dagger)(298) = 33.8 and
      35.1 kcal/mol, respectively). In stark contrast, the reaction of 1 with halogen
      atoms preferentially follows the fragmentation pathway (DeltaG(double
      dagger)(298) = 2.1 and 7.5 kcal/mol) and C-H abstraction is more unfavorable
      (DeltaG(double dagger)(298) = 4.6 and 12.0 kcal/mol). Our computational results
      nicely agree with the behavior of 1 under PT halogenation conditions (where
      Hal(3)C(*) is involved in the activation step) and under free-radical
      photohalogenation with Hal(2) (Della, E. W., et al. J. Am. Chem. Soc. 1992, 114,
      10730). The incorporation of a second halogen atom preferentially in the meta
      position of halocubanes demonstrates the control of the regioselectivity by
      molecular orbital symmetry.

PMID- 11456804
TI  - Kinetic studies of Heck coupling reactions using palladacycle catalysts:
      experimental and kinetic modeling of the role of dimer species.
AB  - Experimental kinetic studies of the coupling of p-bromobenzaldehyde (1) with
      butyl acrylate (2) using the dimeric palladacycles complex (4) with chelating
      nitrogen ligands were carried out together with kinetic modeling using a reaction
      rate expression based on the mechanism shown in Scheme 2. The oxidative addition
      product of 1 was found to be the resting state within the catalytic cycle. The
      formation of dimeric Pd species external to the catalytic cycle helped to
      rationalize a non-first-order rate dependence on catalyst concentration.
      Theoretical modeling showed how the relative concentrations of the different
      intermediate species within the catalystic cycle can influence the observed rate
      dependence on Pd concentration. It was shown how conventional kinetic studies may
      give reaction orders in substrates which differ from those which would be
      observed under practical synthetic conditions. Comparison between phosphine- and
      nonphosphine-based palladacycles suggests that they follow the same reaction
      mechanism. The role of water in accelerating the initial formation of the active
      catalyst species is noted.

PMID- 11456805
TI  - Remarkable control of radical cyclization processes of cyclic enyne: total
      syntheses of (+/-)-methyl gummiferolate, (+/-)-methyl 7beta-hydroxykaurenoate,
      and (+/-)-methyl 7-oxokaurenoate and formal synthesis of (+/-)-gibberellin a(12)
      from a common synthetic precursor.
AB  - Total syntheses of (+/-)-methyl gummiferolate (13b), (+/-)-methyl 7beta
      hydroxykaurenoate (14b), and (+/-)-methyl 7-oxokaurenoate (14d) and a formal
      synthesis of (+/-)-gibberellin A(12) (15) have been accomplished through the
      common synthetic precursor, (3aR,7aR)-3,3-dimethyl-7a-(2-propynyl)-3a,4,7,7a
      tetrahydroisobenzofuranone (16). The homoallyl-homoallyl radical rearrangement
      reaction of the monocyclic enyne 25, derived from 16 in two steps, afforded the
      bicyclo[2.2.2]octane compound 26, which was converted to (+/-)-methyl
      gummiferolate (13b). In contrast, the radical cyclization of the bicyclic enyne
      16 gave the tricyclic lactone 19, leading to (+/-)-methyl 7beta-hydroxykaurenoate
      (14b) and (+/-)-methyl 7-oxokaurenoate (14d). Transformation of 14d into lactone
      20 was carried out in a single step under bromination conditions. This
      constitutes a formal total synthesis of gibberellin A(12) (15).

PMID- 11456806
TI  - First and second generation total synthesis of the teicoplanin aglycon.
AB  - Full details of studies leading to the total synthesis of the teicoplanin aglycon
      are provided. Key elements of the first generation approach (26 steps from
      constituent amino acids, 1% overall) include the coupling of an EFG tripeptide
      precursor to the common vancomycin/teicoplanin ABCD ring system and sequential DE
      macrocyclization of the 16-membered ring with formation of the diaryl ether via a
      phenoxide nucleophilic aromatic substitution of an o-fluoronitroaromatic (80%,
      3:1 atropisomer diastereoselection) followed by 14-membered FG ring closure by
      macrolactamization (66%). Subsequent studies have provided a second generation
      total synthesis which is shorter, more convergent, and highly diastereoselective
      (22 steps, 2% overall). This was accomplished by altering the order of ring
      closures such that FG macrolactamization (95%) preceded coupling of the EFG
      tripeptide to the ABCD ring system and subsequent DE ring closure. Notably, DE
      macrocyclization via diaryl ether formation on substrate 57, the key intermediate
      in the latter approach incorporating the intact FG ring system, occurred with
      exceptional diastereoselection for formation of the natural atropisomer (>10:1,
      76%) without problematic C(2)(3) epimerization provided the basicity of the
      reaction is minimized.

PMID- 11456807
TI  - Enantioselective total synthesis of eunicenone A.
AB  - An enantioselective, stereocontrolled total synthesis of eunicenone A (1) is
      described starting from geranylgeranylacetylene (9) in 14 steps via intermediates
      10-20. The most critical construction in the synthesis is the highly effective
      Diels-Alder combination of the achiral components 2-bromoacrolein and diene 13 in
      the presence of the chiral Lewis acid catalyst 14 to form 15 (85% yield, 97% ee,
      >98:2 endo-exo ratio). The synthesis utilizes a novel reagent (12) for
      introduction of silicon, which serves to activate and direct the diene 13 for
      Diels-Alder reaction and to provide for eventual oxygen functionality of
      homoallylic alcohol 17 under mild conditions. Other noteworthy steps include the
      position selective and diastereoselective epoxidation 17 --> 18, the
      methoxycarbonylation with allylic transposition 19 --> 20, and the alpha,beta
      enone unmasking 20 --> 1.

PMID- 11456808
TI  - Total synthesis and determination of the absolute configuration of frondosin B.
AB  - Two concise syntheses of (+/-)-frondosin B (1), an interleukin-8 receptor
      antagonist, have been achieved from commercially available 5
      methoxysalicylaldehyde. The seven-membered ring in ketone 33, the common
      intermediate for both syntheses, was built by a classical Friedel-Crafts
      reaction. The key step of the first route was facile cationic cyclization of the
      vinylogous benzofuran to the trisubstituted olefin (30 --> 16 + 38) to construct
      a six-membered carbocycle. Although this route demonstrated the efficacy of the
      stepwise approach to the frondosin ring-system, it also resulted in olefinic
      isomers that were easily isomerized in acidic conditions. In the second route, we
      utilized a Diels-Alder reaction between sterically demanding diene 42 and
      nitroethylene to fix the double bond in its required position in the resultant
      dimethylcyclohexane ring. A third total synthesis was devised for the purpose of
      determining the absolute configuration of frondosin B. It reached diene 42, this
      time in the enantiomerically defined form. From this point, naturally configured
      frondosin B was obtained in the enantiomerically enriched form. These studies
      establish the absolute configuration of the secondary methyl center in frondosin
      B to be R.

PMID- 11456809
TI  - Pursuit of optimal carbohydrate-based anticancer vaccines: preparation of a
      multiantigenic unimolecular glycopeptide containing the Tn, MBr1, and Lewis(y)
      antigens.
AB  - A novel preparation of nonnatural glycoamino acids starting from n-pentenyl
      glycosides is described. The approach involves a Horner-Emmons olefination with a
      suitably protected glycine-derived phosphonate, followed by catalytic asymmetric
      hydrogenation, which proceeds with excellent diastereomeric selectivity. The
      synthetic methodology was useful for the preparation of glycoamino acids
      containing the Tn antigen, the MBr1 antigen (Globo-H), the Le(y) antigen, and
      lactose. These glycoamino acids can also serve as units for peptide synthesis.
      The synthesis of polyvalent glycopeptides containing three different antitumor
      antigens is described (28 and 29), and these have been prepared for conjugation
      to carrier protein in order to access the immunogenicity for tumor immunotherapy
      applications.

PMID- 11456810
TI  - Double-strand hydrolysis of plasmid DNA by dicerium complexes at 37 degrees C.
AB  - Significant effort has been made to develop synthetic metal complexes that
      hydrolyze DNA. Here we report a new dicerium complex, Ce(2)(HXTA) (HXTA = 5
      methyl-2-hydroxy-1,3-xylene-alpha,alpha-diamine-N,N,N',N'-tetraacetic acid),
      which can hydrolyze DNA at pH 8 and 37 degrees C. This complex hydrolyzes DNA
      restriction fragments to give products with high regioselectivity, affording >90%
      5'-OPO(3) and 3'-OH ends, like the products of DNA hydrolyzing enzymes.
      Ce(2)(HXTA) also hydrolyzes Litmus 29 plasmid DNA to afford both nicked and
      linear DNA. Analysis of the relative amounts of supercoiled, nicked, and linear
      DNA present show that there is one double-strand cleavage per ten single-strand
      cleavages, indicating that the linear DNA formed cannot be the result of two
      random single-strand cleavage events. The kinetics of nicked and linear DNA
      formation are comparable, both being associated with apparent first-order rate
      constants of approximately 1 x 10(-)(4) s(-)(1) for complex concentrations of 10(
      )(5)-10(-)(4) M. These observations suggest that similar factors affect the
      hydrolysis of the first and second DNA strands and that cleaving the
      phosphodiester bond is likely the rate determining step in both cases. This is
      the first detailed study of a metal complex shown to mimic DNA hydrolases in
      their capability to effect double-strand DNA hydrolysis regioselectively at the
      3'-O-P bond.

PMID- 11456811
TI  - 1H pulsed ENDOR and ESEEM evidence that the bis-imidazole complexes of iron(III)
      tetraphenylchlorin and tetraphenylporphyrin have the same order of g values, and
      the same electronic ground state.
AB  - The electronic structures of the bis-imidazole complexes of iron(III)
      tetraphenylporphyrin ([(TPP)Fe(ImH)(2)](+)) and iron(III) tetraphenylchlorin
      ([(TPC)Fe(ImH)(2)](+)) in frozen glassy solutions have been studied by the pulsed
      electron nuclear double resonance (ENDOR) technique of Mims and by electron spin
      echo envelope modulation (ESEEM) spectroscopy. ESEEM spectra have been used to
      determine the orientation of the imidazole ligand planes with respect to the g
      tensor axes. In the ENDOR spectra, the manifestations of the implicit TRIPLE
      effect described and explained earlier by Doan et al. (J. Am. Chem. Soc. 1996,
      118, 7014) were seen. In this work, the explicit expressions describing this
      effect were derived for the first time and used to successfully simulate the
      proton ENDOR spectra at the low- (LF) and high-field (HF) edges of the EPR
      spectrum. Using pulsed ENDOR, we have been able to determine the spin density
      distributions in the pi-systems of both tetrapyrroles and show that
      [(TPC)Fe(ImH)(2)](+) has the electronic orbital ground state
      (d(xy)())(2)(d(xz)(),d(yz)())(3), the same as that known for
      [(TPP)Fe(ImH)(2)](+), and the largest principal g value corresponds to the g
      tensor axis 3, which is normal to the heme plane. For the TPP complex, the g
      tensor axis 1, corresponding to the smallest principal g value, was found to be
      at an angle phi(1) of 30-35 degrees from the N-Fe-N axis, with the ligand planes
      rotated by the angle of 20-25 degrees in the opposite direction. For the TPC
      complex, phi(1) was found to be about 25 degrees from the direction N(I)-Fe
      N(III), where N(I) corresponds to the nitrogen of the saturated pyrrole ring. The
      ligand planes in this complex were found to be oriented at an angle of about 10
      degrees in the opposite direction.

PMID- 11456812
TI  - Catalysis and inhibition of ligand substitution in palladium(II) square-planar
      complexes: effects of DNA.
AB  - The kinetics of substitution, by thiourea, of ethylenediamine (en) or N,N'
      dimethylethylenediamine (Me(2)en) coordinated to palladium(II) in the complexes
      [Pd(4,4'-R(2)bpy)(en)](PF(6))(2) (bpy = 2,2'-bipyridine; R = H or Me),
      [Pd(en)(2)](PF(6))(2) and [Pd(Me(2)en)(2)](PF(6))(2) have been studied at 25
      degrees C, pH 7 and various ionic strength values, in the presence of calf thymus
      DNA. The rate of the reaction in water depends on ionic strength, pH, and
      nucleophile concentration; at fixed pH and ionic strength the k(obsd) values are
      correlated to the square of the thiourea concentration. This rate law is not
      altered by the presence of DNA, but the rate of reaction is influenced, depending
      on the nature of ancillary ligand, L-L, bound to palladium. DNA inhibits the
      substitution process when L-L is bpy or 4,4'-Me(2)bpy and catalyzes the same
      reaction when L-L is en or Me(2)en. These opposite kinetic effects can be related
      to the noncovalent interactions of the various complexes with the DNA double
      helix. Inhibition of the reactivity of the complexes [Pd(4,4'-R(2)bpy)(en)](2+)
      is due to protection of the reaction center from nucleophile attack by DNA.
      Acceleration of the reaction when L-L is en or Me(2)en is related to the
      dependence of the rate of reaction on pH. If, due to the higher activity of water
      under the electric field of phosphate groups, hydronium ion concentration on DNA
      surface is higher than in the bulk solution, the enzyme-like dependence of the
      rate of reaction on [DNA] is due to progressive accumulation of the complexes
      around the double helix. Regardless of the complexes' nature, the rate constant
      values obtained in DNA at pH 7 correspond to values determined in water at pH 5.
      This pH value on the DNA surface, lower by about two units with respect to the
      bulk solution, is in good agreement with theoretical predictions. Acceleration of
      ethylenediamine substitution has been observed for all of the complexes studied
      in the presence of sodium polyvinylsulfonate.

PMID- 11456813
TI  - Bis(dithiolene)molybdenum analogues relevant to the DMSO reductase enzyme family:
      synthesis, structures, and oxygen atom transfer reactions and kinetics.
AB  - A series of dithiolene complexes of the general type
      [Mo(IV)(QR')(S(2)C(2)Me(2))(2)](1)(-) has been prepared and structurally
      characterized as possible structural and reactivity analogues of reduced sites of
      the enzymes DMSOR and TMAOR (QR' = PhO(-), 2-AdO(-), Pr(i)()O(-)), dissimilatory
      nitrate reductase (QR' = 2-AdS(-)), and formate dehydrogenase (QR' = 2-AdSe(-)).
      The complexes are square pyramidal with the molybdenum atom positioned 0.74-0.80
      A above the S(4) mean plane toward axial ligand QR'. In part on the basis of a
      recent clarification of the active site of oxidized Rhodobacter sphaeroides DMSOR
      (Li, H.-K.; Temple, C.; Rajagopalan, K. V.; Schindelin, H. J. Am. Chem. Soc.
      2000, 122, 7673), we have adopted the minimal reaction paradigm Mo(IV) + XO right
      arrow over left arrow Mo(VI)O + X involving desoxo Mo(IV), monooxo Mo(VI), and
      substrate/product XO/X for direct oxygen atom transfer of DMSOR and TMAOR
      enzymes. The [Mo(OR')(S(2)C(2)Me(2))(2)](1)(-) species carry dithiolene and
      anionic oxygen ligands intended to simulate cofactor ligand and serinate binding
      in DMSOR and TMAOR catalytic sites. In systems with N-oxide and S-oxide
      substrates, the observed overall reaction sequence is
      [Mo(IV)(OR')(S(2)C(2)Me(2))(2)](1)(-) + XO -->
      [Mo(VI)O(OR')(S(2)C(2)Me(2))(2)](1)(-) --> [Mo(V)O(S(2)C(2)Me(2))(2)](1)(-).
      Direct oxo transfer in the first step has been proven by isotope labeling. The
      reactivity of [Mo(OPh)(S(2)C(2)Me(2))(2)](1)(-) (1) has been the most extensively
      studied. In second-order reactions, 1 reduces DMSO and (CH(2))(4)SO (k(2)
      approximately 10(-)(6), 10(-)(4) M(-)(1) s(-)(1); DeltaS(double dagger) = -36, 
      39 eu) and Me(3)NO (k(2) = 200 M(-)(1) s(-)(1); DeltaS(double dagger) = -21 eu)
      in acetonitrile at 298 K. Activation entropies indicate an associative transition
      state, which from relative rates and substrate properties is inferred to be
      concerted with X-O bond weakening and Mo-O bond making. The Mo(VI)O product in
      the first step, such as [Mo(VI)O(OR')(S(2)C(2)Me(2))(2)](1)(-), is an
      intermediate in the overall reaction sequence, inasmuch as it is too unstable to
      isolate and decays by an internal redox process to a Mo(V)O product, liberating
      an equimolar quantity of phenol. This research affords the first analogue
      reaction systems of biological N-oxide and S-oxide substrates that are based on
      desoxo Mo(IV) complexes with biologically relevant coordination. Oxo-transfer
      reactions in analogue systems are substantially slower than enzyme systems based
      on a k(cat)/K(M) criterion. An interpretation of this behavior requires more
      information on the rate-limiting step(s) in enzyme catalytic cycles. (2-Ad = 2
      adamantyl, DMSOR = dimethyl sulfoxide reductase, TMAOR = trimethylamine N-oxide
      reductase)

PMID- 11456814
TI  - Oxo transfer reactions mediated by bis(dithiolene)tungsten analogues of the
      active sites of molybdoenzymes in the DMSO reductase family: comparative
      reactivity of tungsten and molybdenum.
AB  - The discovery of tungsten enzymes and molybdenum/tungsten isoenzymes, in which
      the mononuclear catalytic sites contain a metal chelated by one or two pterin
      dithiolene cofactor ligands, has lent new significance to tungsten-dithiolene
      chemistry. Reaction of [W(CO)(2)(S(2)C(2)Me(2))(2)] with RO(-) affords a series
      of square pyramidal desoxo complexes [W(IV)(OR')(S(2)C(2)Me(2))(2)](1)(-),
      including R' = Ph (1) and Pr(i)() (3). Reaction of 1 and 3 with Me(3)NO gives the
      cis-octahedral complexes [W(VI)O(OR')(S(2)C(2)Me(2))(2)](1)(-), including R' = Ph
      (6) and Pr(i)() (8). These W(IV,VI) complexes are considered unconstrained
      versions of protein-bound sites of DMSOR and TMAOR (DMSOR = dimethylsulfoxide
      reductase, TMAOR = trimethylamine N-oxide reductase) members of the title enzyme
      family. The structure of 6 and the catalytic center of one DMSO reductase
      isoenzyme have similar overall stereochemistry and comparable bond lengths. The
      minimal oxo transfer reaction paradigm thought to apply to enzymes, W(IV) + XO -
      > W(VI)O + X, has been investigated. Direct oxo transfer was demonstrated by
      isotope transfer from Ph(2)Se(18)O. Complex 1 reacts cleanly and completely with
      various substrates XO to afford 6 and product X in second-order reactions with
      associative transition states. The substrate reactivity order with 1 is Me(3)NO >
      Ph(3)AsO > pyO (pyridine N-oxide) > R(2)SO >> Ph(3)PO. For reaction of 3 with
      Me(3)NO, k(2) = 0.93 M(-)(1) s(-)(1), and for 1 with Me(2)SO, k(2) = 3.9 x 10(
      )(5) M(-)(1) s(-)(1); other rate constants and activation parameters are
      reported. These results demonstrate that bis(dithiolene)W(IV) complexes are
      competent to reduce both N-oxides and S-oxides; DMSORs reduce both substrate
      types, but TMAORs are reported to reduce only N-oxides. Comparison of k(cat)/K(M)
      data for isoenzymes and k(2) values for isostructural analogue complexes reveals
      that catalytic and stoichiometric oxo transfer, respectively, from substrate to
      metal is faster with tungsten and from metal to substrate is faster with
      molybdenum. These results constitute a kinetic metal effect in direct oxo
      transfer reactions for analogue complexes and for isoenzymes provided the
      catalytic sites are isostructural. The nature of the transition state in oxo
      transfer reactions of analogues is tentatively considered. This research presents
      the first kinetics study of substrate reduction via oxo transfer mediated by
      bis(dithiolene)tungsten complexes.

PMID- 11456815
TI  - Coordination of Lewis acid to eta(2)-enonepalladium(0) leading to continuous
      structure variation from eta(2)-olefin type to eta(3)-allyl type.
AB  - The reaction of alpha,beta-unsaturated carbonyl compounds, a palladium(0)
      complex, and Lewis acids led to the formation of a new class of complexes showing
      a wide variety of structures with eta(2)-type and eta(3)-type coordination of the
      carbonyl compounds. The reaction of Pd(PhCH=CHCOCH(3))(PPh(3))(2) with
      BF(3).OEt(2) or B(C(6)F(5))(3) quantitatively gave palladium complexes 1a,b
      having BX(3)-coordinated eta(2)-enonepalladium structure, as revealed by X-ray
      structure analysis of the B(C(6)F(5))(3) adduct 1b. On the other hand, the
      reaction of Pd(PhCH=CHCHO)(PPh(3))(2) with BF(3).OEt(2) or B(C(6)F(5))(3) gave
      distorted zwitterionic eta(3)-allylpalladium complexes 3a,b, where the Pd
      carbonyl carbon distance in 3a (2.413(4) A) is much shorter than that (2.96(1) A)
      in 1b. The values of the P-P coupling constant and (13)C chemical shift for
      carbonyl carbon are useful criteria for predicting how the eta(3)-coordination
      mode contributes to the structure of the enone-palladium-Lewis acid system.
      Molecular orbital calculations on the series of model complexes suggest that
      orbital overlap in the highest occupied molecular orbital between the palladium
      and carbonyl carbon is enlarged by coordination of the Lewis acid to the carbonyl
      group. Palladium-catalyzed conjugate addition of R-M (R-M = AlMe(3), AlEt(3),
      ZnEt(2)) and its plausible reaction path are also reported.

PMID- 11456816
TI  - A laser flash photolysis and quantum chemical study of the fluorinated
      derivatives of singlet phenylnitrene.
AB  - Laser flash photolysis (LFP, Nd:YAG laser, 35 ps, 266 nm, 10 mJ or KrF excimer
      laser, 10 ns, 249 nm, 50 mJ) of 2-fluoro, 4-fluoro, 3,5-difluoro, 2,6-difluoro,
      and 2,3,4,5,6-pentafluorophenyl azides produces the corresponding singlet
      nitrenes. The singlet nitrenes were detected by transient absorption
      spectroscopy, and their spectra are characterized by sharp absorption bands with
      maxima in the range of 300-365 nm. The kinetics of their decay were analyzed as a
      function of temperature to yield observed decay rate constants, k(OBS). The
      observed rate constant in inert solvents is the sum of k(R) + k(ISC) where k(R)
      is the absolute rate constant of rearrangement of singlet nitrene to an azirine
      and k(ISC) is the absolute rate constant of nitrene intersystem crossing (ISC).
      Values of k(R) and k(ISC) were deduced after assuming that k(ISC) is independent
      of temperature. Barriers to cyclization of 4-fluoro-, 3,5-difluoro-, 2-fluoro-,
      2,6-difluoro-, and 2,3,4,5,6-pentafluorophenylnitrene in inert solvents are 5.3
      +/- 0.3, 5.5 +/- 0.3, 6.7 +/- 0.3, 8.0 +/- 1.5, and 8.8 +/- 0.4 kcal/mol,
      respectively. The barrier to cyclization of parent singlet phenylnitrene is 5.6
      +/- 0.3 kcal/mol. All of these values are in good quantitative agreement with
      CASPT2 calculations of the relative barrier heights for the conversion of fluoro
      substituted singlet aryl nitrenes to benzazirines (Karney, W. L. and Borden, W.
      T. J. Am. Chem. Soc. 1997, 119, 3347). A single ortho-fluorine substituent exerts
      a small but significant bystander effect on remote cyclization that is not steric
      in origin. The influence of two ortho-fluorine substituents on the cyclization is
      pronounced. In the case of the singlet 2-fluorophenylnitrene system, evidence is
      presented that the benzazirine is an intermediate and that the corresponding
      singlet nitrene and benzazirine interconvert. Ab initio calculations at different
      levels of theory on a series of benzazirines, their isomeric ketenimines, and the
      transition states converting the benzazirines to ketenimines were performed. The
      computational results are in good qualitative and quantitative agreement with the
      experimental findings.

PMID- 11456817
TI  - Solvent and temperature effects on the chiral aggregation of
      poly(alkylarylsilane)s bearing remote chiral groups.
AB  - Novel switchable chiroptical characteristics of poly(alkylarylsilane)
      microaggregates, controllable by the choice of good/poor solvent ratio (solvent
      polarity), solvent addition order, and sample temperature are described. The
      formation of stable chiral aggregates depends critically on the polysilane
      structure and stereochemistry. Poly[n-hexyl-(p-(S)-2-methylbutoxyphenyl)silane]
      (1), optically inactive in molecularly dispersed THF solution due to the
      existence of dynamically equivalent amounts of right (P)- and left (M)-handed
      screw sense helical main chain domains, shows a marked bisignate CD signal due to
      the formation of chiral aggregates in good/poor cosolvent systems. The sign and
      magnitude of the CD signals are dependent on solvent polarity, solvent addition
      order, and thermal effects. The less sterically hindered poly[methyl-(p-(S)-2
      methylbutoxyphenyl)silane] (2) exhibits a weak, bisignate, nonswitchable CD
      signal in only the toluene/acetonitrile system, and no CD signals are evident in
      pure toluene or THF due to masking of the helicity. In contrast, although the
      even less sterically hindered, less polar poly[methyl-(m-(S)-2
      methylbutoxyphenyl)silane] (3) does show optical activity in pure THF or toluene
      (negative CD signal at 310 nm), the CD signal disappears on formation of
      aggregates in good/poor cosolvent systems.

PMID- 11456818
TI  - Quantum chemical investigation of mechanisms of silane oxidation.
AB  - Several mechanisms for the peroxide oxidation of organosilanes to alcohols are
      compared by quantum chemical calculations, including solvation with the PCM
      method. Without doubt, the reaction proceeds via anionic, pentacoordinate
      silicate species, but a profound difference is found between in vacuo and
      solvated reaction profiles, as expected. In the solvents investigated (CH(2)Cl(2)
      and MeOH), the most favorable mechanism is addition of peroxide anion to a
      fluorosilane (starting material or formed in situ), followed by a concerted
      migration and dissociation of hydroxide anion. In the gas phase, and possibly in
      very nonpolar solvents, concerted addition-migration of H(2)O(2) to a
      pentacoordinate fluorosilicate is also plausible.

PMID- 11456819
TI  - The infrared spectrum of the matrix-isolated phenyl radical.
AB  - We have measured the infrared absorption spectrum of C(6)H(5), /X (2)A(1), in an
      Ar matrix at 10 K. The experimental frequencies (cm(-)(1)) and polarizations
      follow. a(1) modes: 3086, 3072, 3037, 1581, 1441, 1154, 1027, 997, 976, 605; b(1)
      modes: 972, 874, 706, 657, 416; b(2) modes: 3071, 3060, 1624, 1432, 1321, 1283,
      1159, 1063, and 587. Three different methods have been used for the production of
      the phenyl radicals. Infrared absorption spectra of five deuterated isotopomers,
      C(6)D(5), p-C(6)H(4)D, p-C(6)HD(4), o-C(6)H(4)D, and m-C(6)H(4)D, were recorded
      to compare experimental frequency shifts with calculated (UB3LYP/cc-pVDZ)
      harmonic frequency shifts. The use of CO(2) or NO as internal standards enabled
      the experimental determination of absolute infrared intensities. The linear
      dichroism was measured with photooriented samples to establish experimental
      polarizations of each vibrational band. True gas-phase vibrational frequencies
      were estimated by considering the gas-to-matrix shifts and matrix inhomogeneous
      line broadening. The phenyl radical matrix frequencies listed above are within +/
      1% of the gas-phase vibrational frequencies. The C(6)H(5) frequencies from this
      paper supersede our earlier values reported in J. Am. Chem. Soc. 1996, 118, 7400
      7401. See also: http://ellison.colorado.edu/phenyl.

PMID- 11456820
TI  - Oligomer-oligomer versus oligomer-monomer C(2)-C(2)' coupling reactions in
      polypyrrole growth.
AB  - The C(2)-C(2)' coupling reactions of oligopyrrole radical-cations of increasing
      length generated by electrochemical oxidation have been modeled by transition
      state calculations. The modeling approach takes into account solvent effects and
      (i) shows that the coupling distance in the transition state decreases with
      oligomer length, (ii) demonstrates that dimerization rates in the gas phase
      decrease with oligomer length but increase in water, (iii) suggests that in a
      less solvating medium the dimerization rates could be equivalent, (iv) indicates
      that in all solvents quaterpyrrole and sexipyrrole formation is faster through a
      coupling reaction between oligomer and monomer radical-cations than two oligomer
      radical-cations, and (v) suggests that for the formation of a long oligopyrrole
      from oligopyrrole-pyrrole reactions the mechanism might involve the coupling of
      the oligopyrrole dication with a non-oxidized pyrrole unit instead of the
      coupling of two radical-cations or that of the oligopyrrole dication with a
      pyrrole radical-cation.

PMID- 11456821
TI  - Infrared spectrum of the hyponitrite dianion, N(2)O(2)2-, isolated and insulated
      from stabilizing metal cations in solid argon.
AB  - Ultraviolet irradiation of a rigid 7 K argon matrix containing alkali or alkaline
      earth metal atoms and NO(2) isolated from each other by one or two layers of
      argon forms N(2)O(2)2-dianions insulated from two M(+) cations by argon atoms,
      and visible photolysis reverses this electron-transfer process likely involving
      the N(2)O(2)(-) anion intermediate. The isolated N(2)O(2)2- dianion is identified
      from isotopic substitution and isotopic mixtures, which show that the new 1028.5
      cm(-1) metal independent absorption involves two equivalent NO subunits. DFT
      calculations predict a strong 1078.1 cm(-1) fundamental for the Li(NO)(2)Li
      molecule and isotopic frequency ratios in excellent agreement with the observed
      values, which provides a model for the matrix dianion system. The spectrum of
      solid Na(2)N(2)O(2) exhibits a 1030 cm(-1) infrared band, which strongly supports
      the present N(2)O(2)2- dianion assignment. The electrostatic stabilization of
      N(2)O(2)2-, which is probably unstable in the gas phase, is made possible by
      metal cations separated by one or two insulating layers of argon in the rigid 7 K
      matrix.

PMID- 11456822
TI  - An NMR and ab initio quantum chemical study of acid-base equilibria for
      conformationally constrained acidic alpha-amino acids in aqueous solution.
AB  - The protonation states of a series of piperidinedicarboxylic acids (PDAs), which
      are conformationally constrained acidic alpha-amino acids, have been studied by
      (13)C NMR titration in water. The resulting data have been correlated with
      theoretical results obtained by HF/6-31+G calculations using the polarizable
      continuum model (PCM) for the description of water. The PDAs are highly ionizable
      and contain one or two possible internal hydrogen bonds. In the present study, we
      show that the PCM model is able to reproduce the relative stabilities of the
      different protonation states of the PDAs. Furthermore, our results show that
      prediction of relative pK(a) values for two different types of ionizable
      functional groups covering a pK(a) range from 1.6 to 12.1 is possible with a high
      degree of accuracy.

PMID- 11456823
TI  - Variational principles for describing chemical reactions. Reactivity indices
      based on the external potential.
AB  - In a recent paper [J. Am. Chem. Soc. 2000, 122, 2010], the authors explored
      variational principles that help one understand chemical reactivity on the basis
      of the changes in electron density associated with a chemical reaction. Here,
      similar methods are used to explore the effect changing the external potential
      has on chemical reactivity. Four new indices are defined: (1) a potential energy
      surface that results from the second-order truncation of the Taylor series in the
      external potential about some reference, Upsilon(R(1),R(2),.,R(M)()); (2) the
      stabilization energy for the equilibrium nuclear geometry (relative to some
      reference), Xi; (3) the flexibility, or "lability", of the molecule at
      equilibrium, Lambda; and (4) the proton hardness, Pi, which performs a role in
      the theory of Bronsted-Lowry acids and bases that is similar to the role of the
      chemical hardness in the theory of Lewis acids and bases. Applications considered
      include the orientation of a molecule in an external electric field, molecular
      association reactions, and reactions between Bronsted-Lowry acids and bases.

PMID- 11456824
TI  - On the importance of prereactive complexes in molecule-radical reactions:
      hydrogen abstraction from aldehydes by OH.
AB  - In this work, the OH + formaldehyde and OH + acetaldehyde reactions have been
      characterized using accurate ab initio methods with large basis sets. The results
      clearly indicate that the reaction occurs by hydrogen abstraction, and that the
      OH addition channel is unfavorable. Close to zero (for formaldehyde) and negative
      (for acetaldehyde) activation energy values are obtained, which are in excellent
      agreement with the experimentally observed values. The reaction rate constants,
      calculated using the classical transition-state theory as applied to a complex
      mechanism involving the formation of a prereactive complex, reproduce very well
      the reported experimental results. Consideration of the prereactive complex is
      shown to be essential for the determination of the height of the energy barrier
      and thus for the correct calculation of the tunneling factor.

PMID- 11456825
TI  - Reductive dechlorination of hexachloroethane in the environment: mechanistic
      studies via computational electrochemistry.
AB  - Ab initio and density functional levels of electronic structure theory are
      applied to characterize alternative mechanisms for the reductive dechlorination
      of hexachloroethane (HCA) to perchloroethylene (PCE). Aqueous solvation effects
      are included using the SM5.42R continuum solvation model. After correction for a
      small systematic error in the electron affinity of the chlorine atom, theoretical
      predictions are accurate to within 23 mV for four aqueous reduction potentials
      relevant to HCA. A single pathway that proceeds via two successive single
      electron transfer/barrierless chloride elimination steps, is predicted to be the
      dominant mechanism for reductive dechlorination. An alternative pathway predicted
      to be accessible involves trichloromethylchlorocarbene as a reactive
      intermediate. Bimolecular reactions of the carbene with other species at
      millimolar or higher concentrations are predicted to potentially be competitive
      with its unimolecular rearrangement to form PCE.

PMID- 11456826
TI  - Segmental dynamics of interfacial poly(methyl acrylate)-d(3) in composites by
      deuterium NMR spectroscopy.
AB  - The interface in composite materials containing an ultrathin layer of poly(methyl
      acrylate)-d(3) (PMA-d(3)) on silica was studied using deuterium NMR. PMA-d(3) was
      deposited from solution at saturation coverage from toluene onto silica. The
      samples were dried and composite samples made by hot pressing the PMA-d(3)/silica
      samples with hydrogenated polystyrene (PS) and high (HMW) and low (LMW) molecular
      weight hydrogenated poly(methyl acrylate) (PMA) as the overlayer. The interfacial
      layers of PMA-d(3) were studied at the air-polymer-silica and polymer-polymer
      silica interfaces using deuterium solid-state quadrupole-echo NMR and the results
      compared to those for the bulk polymer. It was found that for samples at the air
      polymer-silica interface, some of the polymer segments in the surface sample had
      segmental mobility higher than that of the corresponding bulk PMA-d(3) sample at
      the same temperature. When overcoated with unlabeled polymer, the interfacial
      polymer at the polymer-polymer-silica interface showed reduced mobility due to
      the presence of the overlayer. The adsorbed PMA-d(3), in the composite samples,
      decreased in mobility in the order of LMW-PMA > HMW-PMA > PS. The PS sample
      caused the greatest reduction in the PMA-d(3) interfacial mobility. The order was
      consistent with the segmental mobilities of the polymers used for the overlayers.
      The lower the mobility of the polymer used for the overlayer, the more restricted
      were the polymer segments in the adsorbed PMA-d(3) layer.

PMID- 11456827
TI  - Solvent effects on the thioamide rotational barrier: an experimental and
      theoretical study.
AB  - The solvent effect on the C-N rotational barriers of N,N-dimethylthioformamide
      (DMTF) and N,N-dimethylthioacetamide (DMTA) has been investigated using ab initio
      theory and NMR spectroscopy. Selective inversion recovery NMR experiments were
      used to measure rotational barriers in a series of solvents. These data are
      compared to ab initio results at the G2(MP2) theoretical level. The latter are
      corrected for large amplitude vibrational motions to give differences in free
      energy. The calculated gas phase barriers are in very good agreement with the
      experimental values. Solvation effects were calculated using reaction field
      theory. This approach has been found to give barriers that are in good agreement
      with experiment for many aprotic, nonaromatic solvents that do not engage in
      specific interactions with the solute molecules. The calculated solution-phase
      barriers for the thioamides using the above solvents are also in good agreement
      with the observed barriers. The solvent effect on the thioamide rotational
      barrier is larger than that for the amides because the thioamides have a larger
      ground-state dipole moment, and there is a larger change in dipole moment with
      increasing solvent polarity. The transition-state dipole moments for the amides
      and thioamides are relatively similar. The origin of the C-N rotational barrier
      and its relation to the concept of amide "resonance" is examined.

PMID- 11456828
TI  - Hydrogen-bond mediated catalysis: the aminolysis of 6-chloropyrimidine as
      catalyzed by derivatives of uracil.
AB  - The aminolysis of 6-chloropyrimidine and 2-amino-6-chloropyrimidine has been
      examined by using density functional theory. Relative to the aminolysis of 6
      chloropyrimidine, the addition of an electron-donating NH(2) group to C(2)
      increases the barrier to aminolysis, indicating that the third hydrogen bond does
      not play a catalytic role but introduces additional rigidity into the system.
      However, the computations suggest that there is an interesting correlation
      between the barrier to aminolysis and the proton affinity of the species that
      interacts with the incoming NH(3). To extend the range of proton affinities, the
      aminolysis of 6-chloropyrimidine was examined by using fluoro, imine, and
      thioketo derivatives of the uracil-derived bases. The proton affinity of the
      moiety that hydrogen bonds with NH(3) is decreased by fluoro substitution, and
      thus the aminolysis barriers are increased. Similarly, imine substitution
      enhances the PA of the moiety, which is reflected in a decrease in the aminolysis
      barriers. The same correlation exists for the thioketo-derived bases, whose PAs
      are intermediate between the fluoro and imine derivatives. Thus, the aminolysis
      of 6-chloropryimidine and 2-amino-6-chloropyrimidine demonstrates the importance
      of a well-chosen proton acceptor and the catalytic possibilities associated with
      the formation of multiple hydrogen bonds.

PMID- 11456829
TI  - How far do electrons move? A semiempirical investigation of thermal electron
      transfer distances in cationic bis(hydrazine) and bis(hydrazyl) mixed-valence
      compounds.
AB  - A computational approach for estimating thermal electron-transfer reaction
      distances in symmetrical mixed-valence compounds is described and applied to a
      series of bis(hydrazine) and bis(hydrazyl) radical cations and derivatives, some
      of which have been investigated experimentally by Nelsen and co-workers. Ground
      state semiempirical charge distributions are obtained by using optimized reactant
      geometries. Advantage is then taken of the approximate C(2) symmetry, or the
      approximate mirror symmetry, of each of the targeted compounds, and the inherent
      degeneracy of the corresponding electron-transfer reactions, such that the change
      in dipole moment (Delta-mu) upon charge transfer can be estimated from an
      appropriately distance-weighted sum of charge differences between approximately
      symmetry-equivalent atoms found on the donor and acceptor sides of the molecule.
      Delta-mu can then be related directly to the effective one-electron-transfer
      distance. We find that calculated adiabatic electron-transfer distances can
      differ appreciably from the geometric donor-site/acceptor-site separation
      distances. Furthermore, for a fixed geometric separation distance, the effective
      electron-transfer distance can vary considerably, depending on chemical
      substituent composition and/or isomeric configuration. Further advantage is taken
      of the approximate donor-site/acceptor-site symmetry, in the context of a Newton
      Cave type analysis, to establish the relative importance of electronic
      delocalization effects versus self-polarization and inductive effects in
      diminishing or enhancing effective one-electron-transfer distances.

PMID- 11456830
TI  - Carbon nanotubes as superior sorbent for dioxin removal.

PMID- 11456832
TI  - A highly active well-defined rhenium heterogeneous catalyst for olefin metathesis
      prepared via surface organometallic chemistry.

PMID- 11456831
TI  - Thiol-independent DNA alkylation by leinamycin.

PMID- 11456833
TI  - The energetic contribution of a bifurcated hydrogen bond to the binding of DAPI
      to dA-dT rich sequences of DNA.

PMID- 11456834
TI  - (131)Xe, a new NMR probe of void space in solids.

PMID- 11456835
TI  - NMR study of monomer-dimer equilibrium of barstar in solution.

PMID- 11456836
TI  - Catalytic asymmetric C-H activation of silyl enol ethers as an equivalent of an
      asymmetric Michael reaction.

PMID- 11456837
TI  - Synthetic peptide receptors: molecularly imprinted polymers for the recognition
      of peptides using peptide-metal interactions.

PMID- 11456838
TI  - A novel Cu-assisted cycloisomerization of alkynyl imines: efficient synthesis of
      pyrroles and pyrrole-containing heterocycles.

PMID- 11456839
TI  - Toward creation of a universal NMR database for stereochemical assignment:
      complete structure of the desertomycin/oasomycin class of natural products.

PMID- 11456840
TI  - Enhanced triple helix stability of collagen peptides with 4R-aminoprolyl (Amp)
      residues: relative roles of electrostatic and hydrogen bonding effects.

PMID- 11456841
TI  - Sugar nucleotide regeneration beads (superbeads): a versatile tool for the
      practical synthesis of oligosaccharides.

PMID- 11456843
TI  - H-H distances in elongated transition metal dihydrogen complexes: effects of
      temperature and isotopic substitution.

PMID- 11456842
TI  - Configuration-dependent heat capacity of pairwise hydrophobic interactions.

PMID- 11456844
TI  - Formation of unsymmetrical polyoxotungstates via transfer of polyoxometalate
      building blocks. NMR evidence supports the kinetic stability of the
      pentatungstate anion, [W(5)O(18)]6-, in aqueous solution.

PMID- 11456845
TI  - Palladium-catalyzed asymmetric synthesis of axially chiral allenes: a synergistic
      effect of dibenzalacetone on high enantioselectivity.

PMID- 11456846
TI  - Stereoselective generation of E- and Z-disubstituted amide enolates. Reductive
      enolate formation from bicyclic thioglycolate lactams.

PMID- 11456847
TI  - Unexpected entropy-driven ring-opening polymerization in a reversible
      supramolecular system.

PMID- 11456848
TI  - Application of Baldwin's rules for the preparation of stable, beta-leaving group
      bearing organolithium compounds.

PMID- 11456849
TI  - Total synthesis of (+/-)-epoxysorbicillinol.

PMID- 11456850
TI  - Synthesis of novel expanded calixphyrins: anion binding properties of a
      calix[6]phyrin with a deep cavity.

PMID- 11456852
TI  - Chemical cross-linking, surface compressional modulus, and viscosity of n
      octadecyltrimethoxy silane monolayers.

PMID- 11456851
TI  - Growth of ionic crystals in carbon nanotubes.

PMID- 11456853
TI  - Electrochemical AFM "dip-pen" nanolithography.

PMID- 11456854
TI  - Conformational restriction of flexible ligands guided by the transferred noe
      experiment: potent macrocyclic inhibitors of farnesyltransferase.

PMID- 11456855
TI  - Carbon monoxide binding by de novo heme proteins derived from designed
      combinatorial libraries.
AB  - Carbon monoxide binding was studied in a collection of de novo heme proteins
      derived from combinatorial libraries of sequences designed to fold into 4-helix
      bundles. The design of the de novo sequences was based on the previously reported
      "binary code" strategy, in which the patterning of polar and nonpolar amino acids
      is specified explicitly, but the exact identities of the side chains are varied
      extensively.(1) The combinatorial mixture of amino acids included histidine and
      methionine, which ligate heme iron in natural proteins. However, no attempt was
      made to explicitly design a heme binding site. Nonetheless, as reported
      previously, approximately half of the binary code proteins bind heme.(2) This
      collection of novel heme proteins provides a unique opportunity for an unbiased
      assessment of the functional potentialities of heme proteins that have not been
      prejudiced either by explicit design or by evolutionary selection. To assess the
      capabilities of the de novo heme proteins to bind diatomic ligands, we measured
      the affinity for CO, the kinetics of CO binding and release, and the resonance
      Raman spectra of the CO complexes for eight de novo heme proteins from two
      combinatorial libraries. The CO binding affinities for all eight proteins were
      similar to that of myoglobin, with dissociation constants (K(d)) in the low
      nanomolar range. The CO association kinetics (k(on)) revealed that the heme
      environment in all eight of the de novo proteins is partially buried, and the
      resonance Raman studies indicated that the local environment around the bound CO
      is devoid of hydrogen-bonding groups. Overall, the CO binding properties of the
      de novo heme proteins span a narrow range of values near the center of the range
      observed for diverse families of natural heme proteins. The measured properties
      of the de novo heme proteins can be considered as a "default" range for CO
      binding in alpha-helical proteins that have neither been designed to bind heme or
      CO, nor subjected to genetic selections for heme or CO binding.

PMID- 11456856
TI  - Tuning the strain and polymerizability of organometallic rings: the synthesis,
      structure, and ring-opening polymerization behavior of [2]ferrocenophanes with C
      SI, C-P, and C-S bridges.
AB  - A series of novel [2]ferrocenophanes with unsymmetrical C-E bridges has been
      prepared in which the covalent radius of the second-row element, E, and hence the
      ring strain present is varied. Species [Fe(eta-C(5)Me(4))(eta
      C(5)H(4))CH(2)ER(x)] (7, ER(x) = SiMe(2); 8a, ER(x) = PPh; 8b, ER(x) = PMes; 9,
      ER(x) = S) were synthesized via reaction of the PMDETA (N,N,N',N' ',N' '
      pentamethyldiethylenetriamine) adduct of [(eta-C(5)H(4)Li)Fe(eta
      C(5)Me(4))CH(2)Li] with Cl(2)ER(x) (E = Si or P) or S(SO(2)Ph)(2). Studies of 7-9
      by single-crystal X-ray diffraction confirmed the presence of ring-tilted
      structures: for 7, alpha (angle between the planes of the Cp rings) = 11.8(1)
      degrees; for 8a, alpha(average) = 14.9(3) degrees; for 8b, alpha(average) =
      18.2(2) degrees; and for 9, alpha = 18.5(1) degrees. The least tilted compound,
      7, was found to be resistant to thermal, anionic, and transition metal catalyzed
      ROP. In contrast, the significantly more tilted compounds 8a, 8b, and 9 were all
      found to polymerize thermally with small negative values of DeltaH(ROP) of ca. 10
      20 kJ.mol(-1) determined by DSC. Whereas thermal ROP of 8a yielded the soluble
      high molecular weight polycarbophosphaferrocene [(eta-C(5)Me(4))Fe(eta
      C(5)H(4))CH(2)PPh](n) (11), species 9 formed the insoluble polycarbothiaferrocene
      [(eta-C(5)Me(4))Fe(eta-C(5)H(4))CH(2)S](n) (14). Attempted anionic ROP of 8a and
      9 with (n)BuLi was unsuccessful and treatment of 8a with CF(3)SO(3)Me resulted in
      the formation of the novel phosphonium salt [(eta-C(5)Me(4))Fe(eta
      C(5)H(4))CH(2)PMePh][CF(3)SO(3)] (13), which was found to be resistant to thermal
      ROP as a result of its less strained structure (for 13, alpha = 11.4(7) degrees
      ). Treatment of 9 with CF(3)SO(3)Me or BF(3).Et(2)O resulted in the first example
      of cationic ROP for a transition metal-containing heterocycle to yield
      polycarbothiaferrocene 14. In the presence of excess 2,6-di-tert-butylpyridine as
      a selective proton trap, ROP of 9 was only observed with CF(3)SO(3)Me, and not
      BF(3).Et(2)O, which indicated that Me(+) and H(+) are the probable cationic
      initiators, respectively. Thermal copolymerization of 9 with trimethylene sulfide
      resulted in the isolation of the soluble, high molecular weight, random copolymer
      [(eta-C(5)Me(4))Fe(eta-C(5)H(4))CH(2)S](n)[(CH(2))(3)S](m), 15.

PMID- 11456857
TI  - The importance of model studies in computational organic synthesis.
AB  - We explore a model, the "synthesis engine", for synthesis of arbitrarily complex
      organic structures in the context of library construction of Grignard cycle
      compounds. We use the simplest possible governing logic and show that random
      synthesis produces an extremely uneven distribution of products over several
      target structure types. We show that the question of "synthetic power" may be
      addressed computationally in this model system.

PMID- 11456858
TI  - Electronic control of the Bergman cyclization: the remarkable role of vinyl
      substitution.
AB  - We report an ab initio study of the effect of vinyl substitution on the
      cycloaromatization of 3-ene-1,5-diynes (the Bergman cyclization). The majority of
      the calculations were conducted by using the BLYP version of Density Functional
      Theory, and higher level Brueckner orbital calculations were used for a few key
      compounds. In all, 46 enediynes, 44 cyclization transition states, 39 singlet p
      benzynes, and 28 related triplet p-benzynes were studied, including simple vinyl
      substituted and annulated examples. The data indicate that strongly electron
      withdrawing groups increase the cyclization barrier, while sigma-donating groups
      decrease it; pi conjugation, especially donation, has little effect. Most
      annulations, including those involving heteroaromatic rings, lower the barrier
      slightly (6 MR) or raise it slightly (5 MR). Larger effects are seen for smaller
      rings or charged rings. Some previously observed apparent rate inhibitions are
      seen to be due to reversibility or forward reactivity of the intermediate p
      benzynes, which are thereby inhibited from the H abstraction step that completes
      cycloaromatization. H abstraction reactivity, as judged from the p-benzyne
      singlet-triplet energy gap and from isodesmic equations, is also examined.
      Unexpected behavior is predicted for some heteroaromatic systems. Finally, we
      anticipate how these results may be applied to the design of prodrug candidates
      for subsequent biological application.

PMID- 11456859
TI  - Target analogue imprinted polymers with affinity for folic acid and related
      compounds.
AB  - Two approaches to synthesize molecularly imprinted polymers with affinity for
      folic acid and other substituted pteridines have been compared. In the first
      approach, the folic acid analogue methotrexate was used as template and
      functional monomers capable of generating selective binding sites were searched
      in a miniaturized screening system based on binding assessment in the batch mode.
      Highest selectivity was seen using 2-vinylpyridine as functional monomer, which
      was confirmed in the chromatographic mode for a batch synthesized on a gram
      scale. However, the retentivity and selectivity of this phase were insufficient
      for anticipated applications. In a second approach, using methacrylic acid as the
      functional monomer, organic soluble inhibitors for the enzyme dihydrofolate
      reductase were used to develop sites complementary toward the pteridine
      substructure. This resulted in materials showing enhanced selectivity for
      substituted pteridines when evaluated by HPLC. Thus, methotrexate and leucovorine
      were selectively retained in mobile phases of either low or high aqueous content,
      thus showing the typical bimodal retention behavior of previously reported MIPs.
      In organic mobile-phase systems, the inhibitor used as template had an influence
      on the retentivity and selectivity of the MIP. The polymer imprinted with
      trimethoprim retained all folic acid analogues strongly and showed the highest
      selectivity among the MIPs in an organic mobile-phase system. This was supported
      by Scatchard analysis resulting in biphasic plots and a quantitative yield of
      high-energy binding sites. All templates were shown to associate strongly with
      MAA in CDCl(3), the strength of association correlating roughly with the template
      basicity and the selectivity observed in chromatography. Nonparallel complexation
      induced shifts indicated formation of 1:2 template monomer complexes at
      concentrations corresponding to those of the prepolymerization solutions.

PMID- 11456860
TI  - Unraveling structure-reactivity relationships in SNV reactions: kinetics of the
      reactions of methoxybenzylidenemalononitrile, 2-(methylthiobenzylidene)-1,3
      indandione, 2-(benzylthiobenzylidene)-1,3-indandione, and methyl beta-methylthio
      alpha-nitrocinnamate with OH- and thiolate ions in aqueous DMSO.
AB  - The kinetics of the title reactions were determined in 50% DMSO-50% water (v/v)
      at 20 degrees C; n-BuS-, HOCH2CH2S-, and MeO2CCH2S- were used as thiolate ions.
      The reactions with the thiolate ions gave rise to two separate kinetic processes.
      The first refers to rapid, reversible attachment of RS- to the substrate leading
      to a tetrahedral intermediate (k1RS), k(-1)RS, the second to the conversion of
      the intermediate to products (k2RS). In most cases all of the rate constants
      (k1RS, k(-1)RS and k2RS could be determined. In combination with results from
      previous studies, a detailed discussion regarding the effects of activating
      substituents and leaving groups on rate and equilibrium constants as well as on
      intrinsic rate constants is presented. The reaction with OH- only allowed a
      determination of k1OH for nucleophilic attack on the substrate; in this case the
      tetrahedral intermediate remains at steady-state levels under all conditions.

PMID- 11456861
TI  - Effects of metal ions on physicochemical properties and redox reactivity of
      phenolates and phenoxyl radicals: mechanistic insight into hydrogen atom
      abstraction by phenoxyl radical-metal complexes.
AB  - Phenolate and phenoxyl radical complexes of a series of alkaline earth metal ions
      as well as monovalent cations such as Na+ and K+ have been prepared by using 2,4
      di-tert-butyl-6-(1,4,7,10-tetraoxa-13-aza-cyclopentadec-13-ylmethyl)phenol (L1H)
      and 2,4-di-tert-butyl-6-(1,4,7,10,13-pentaoxa-16-aza-cyclooctadec-16
      ylmethyl)phenol (L2H) to examine the effects of the cations on the structure,
      physicochemical properties and redox reactivity of the phenolate and phenoxyl
      radical complexes. Crystal structures of the Mg2+- and Ca2+-complexes of L1- as
      well as the Ca2+- and Sr2+-complexes of L2- were determined by X-ray
      crystallographic analysis, showing that the crown ether rings in the Ca2+
      complexes are significantly distorted from planarity, whereas those in the Mg2+-
      and Sr2+-complexes are fairly flat. The spectral features (UV-vis) as well as the
      redox potentials of the phenolate complexes are also influenced by the metal
      ions, depending on the Lewis acidity of the metal ions. The phenoxyl radical
      complexes are successfully generated in situ by the oxidation of the phenolate
      complexes with (NH4)(2)[Ce4+(NO3)6] (CAN). They exhibited strong absorption bands
      around 400 nm together with a broad one around 600-900 nm, the latter of which is
      also affected by the metal ions. The phenoxyl radical-metal complexes are
      characterized by resonance Raman, ESI-MS, and ESR spectra, and the metal ion
      effects on those spectroscopic features are also discussed. Stability and
      reactivity of the phenoxyl radical-metal complexes are significantly different,
      depending on the type of metal ions. The disproportionation of the phenoxyl
      radicals is significantly retarded by the electronic repulsion between the metal
      cation and a generated organic cation (Ln+), leading to stabilization of the
      radicals. On the other hand, divalent cations decelerate the rate of hydrogen
      atom abstraction from 10-methyl-9,10-dihydroacridine (AcrH2) and its 9
      substituted derivatives (AcrHR) by the phenoxyl radicals. On the basis of primary
      kinetic deuterium isotope effects and energetic consideration of the electron
      transfer step from AcrH2 to the phenoxyl radical-metal complexes, we propose that
      the hydrogen atom abstraction by the phenoxyl radical-alkaline earth metal
      complexes proceeds via electron transfer followed by proton transfer.

PMID- 11456862
TI  - alpha-Ketocarbonyl peptides: a general approach to reactive resin-bound
      intermediates in the synthesis of peptide isosteres for protease inhibitor
      screening on solid support.
AB  - alpha-Ketocarbonyl peptides were generated from peptide precursors on solid
      support via a metal-ion-catalyzed transamination. The reaction proceeded to
      completion within 2 h with glyoxylate as electrophile and copper(II) ions as
      catalyst in an aqueous acetate buffer at pH 5.5-6.0. The variety of naturally
      occurring alpha-amino acid substrates gave rise to a diverse set of
      differentially functionalized ketones. The highly reactive terminal ketocarbonyls
      were prone to aldol-type dimerization and could be transferred into stable
      moieties by oxime formation, reduction to the alcohol, or reductive amination,
      respectively. The alpha-ketocarbonyl peptides were efficient in nucleophilic
      addition of C-nucleophiles such as phosphono-ylides and allylsilanes.

PMID- 11456863
TI  - Dodecahydroxy-closo-dodecaborate(2-).
AB  - The cesium salt of the icosahedral borane anion dodecahydroxy-closo
      dodecaborate(2-), Cs(2)[closo-B(12)(OH)(12)], Cs(2)1, was prepared by heating
      cesium dodecahydro-closo-dodecaborate(2-), Cs(2)[closo-B(12)H(12)], Cs(2)2, with
      30% hydrogen peroxide. The other alkali metal salts A(2)1 (A = Li, Na, K, Rb)
      precipitated upon addition of ACl to warm aqueous solutions of Cs(2)1. The
      ammonium salt, [NH(4)](2)1, and the (mu-nitrido)bis(triphenylphosphonium) salt,
      [PPN](2)1, were obtained similarly. The [H(3)O](2)1 salt precipitated upon
      acidification of aqueous solutions of Cs(2)1 with hydrochloric acid. The
      solubility of these salts in water was determined by measuring the boron content
      of saturated aqueous solutions of A(2)1 (A = Li, Na, K, Rb, Cs), [H(3)O](2)1, and
      [NH(4)](2)1 using ICP-AES. Although these salts are derived from a dianion with
      twelve pendant hydroxyl groups, the alkali metal salts surprisingly displayed low
      water solubilities. Water solubility decreases with a decrease in the radius of
      A(+), except for the lithium salt, which is slightly more soluble than the
      potassium salt. The [H(3)O](2)1 and the [NH(4)](2)1 salts provide rare examples
      of water-insoluble hydronium and ammonium salts. The low water solubility of the
      A(2)1 salts is attributed to the dianion's pendant hydroxyl groups, which appear
      to function as cross-linking ligands. Four alkali metal salts, A(2)1 (A = Na, K,
      Rb, Cs), were characterized in the solid state by single-crystal X-ray
      crystallography. These data revealed intricate networks in which several anions
      are complexed through their hydroxyl groups to each alkali metal cation. In
      addition, the anions are engaged in hydrogen bonding with each other and, if
      present, with water of hydration. This cross-linking results in the precipitation
      of aggregated salts. Cation coordination numbers decrease with cation radius.
      Thus, cesium and rubidium are ten-coordinate, whereas potassium is seven
      coordinate and sodium is six-coordinate. The geometry of anion 1(2)(-) is
      independent of cation identity; the B-B and B-O bond lengths of the various A(2)1
      salts (A = Na, K, Rb, Cs) are identical.

PMID- 11456864
TI  - De novo design and characterization of copper centers in synthetic four-helix
      bundle proteins.
AB  - The design and chemical synthesis of de novo metalloproteins on cellulose
      membranes with the structure of an antiparallel four-helix bundle is described.
      All possible combinations of three different sets of amphiphilic helices were
      assembled on cyclic peptide templates which were bound by a cleavable linker to
      the cellulose. In the hydrophobic interior, the four-helix bundle proteins carry
      a cysteine and several histidines at various positions for copper ligation. This
      approach was used successfully to synthesize, for the first time, copper proteins
      based on a four-helix bundle. UV-vis spectra monitored on the solid support
      showed ligation of copper(II) by about one-third out of the 96 synthesized
      proteins and tetrahedral complexes of cobalt(II) by most of these proteins. Three
      of the most stable copper-binding proteins were synthesized in solution and their
      structural properties analyzed by spectroscopic methods. Circular dichroism, one
      dimensional NMR, and size-exclusion chromatography indicate a folding into a
      compact state containing a high degree of secondary structure with a reasonably
      ordered hydrophobic core. They displayed UV-vis absorption, resonance Raman, and
      EPR spectra intermediate between those of type 1 and type 2 copper centers. The
      present approach provides a sound basis for further optimizing the copper binding
      and its functional properties by using combinatorial protein chemistry guided by
      rational principles.

PMID- 11456865
TI  - Continuous crystalline carbonate apatite thin films. A biomimetic approach.
AB  - In contrast to extensive studies on hydroxyapatite thin films, very little has
      been reported on the thin films of carbonated apatite (dahllite). In this report,
      we describe the synthesis and characterization of a highly crystalline dahllite
      thin film assembled via a biomimetic pathway. A free-standing continuous
      precursor film of carbonated calcium phosphate in an amorphous phase was first
      prepared by a solution-inhibited templating method (template-inhibition) at an
      air-water interface. A stearic acid surface monolayer acted as the template,
      while a carbonate-phosphate solution composed a binary inhibition system. The
      precursor film formed at the air/water interface was heated at 900 degrees C and
      transformed into a dense crystalline film that retained the overall shape of the
      precursor. The crystalline phase was characterized by XRD and IR to be a single
      phase carbonate apatite, with carbonate substitutions in both type A (OH-) and
      type B (PO4(3-)) lattice positions.

PMID- 11456866
TI  - Ti location in the MFI framework of Ti-Silicalite-1: a neutron powder diffraction
      study.
AB  - The first direct evidence that Ti atoms are not equally distributed in the 12
      crystallographically independent T sites of the MFI framework is presented on the
      basis of neutron diffraction data collected at the HRPD instrument of the ISIS
      pulsed neutron source. We found strong evidence indicating that T6, T7, and T11
      are the most populated sites and weak evidence that Ti may be hosted in T10. Ti
      occupancy can be excluded for sites T1, T2, T4, T5, T9, and T12. The occupancy of
      the remaining sites is doubtful. Since defective silicalite has been shown to
      exhibit the same preferential sites (T6, T7, T11, and T10) for Si vacancies, it
      may be suggested that the incorporation mechanism of the Ti atoms in the MFI
      framework occurs via the insertion of titanium in the defective sites. This
      hypothesis implies that titanium has a mineralizing effect on the MFI framework,
      and it is supported by independent spectroscopic data on both TS-1 and defective
      silicalite. The results are discussed in comparison with the known substitution
      mechanisms in the T-sites of MFI-type structures.

PMID- 11456867
TI  - Electronic structure of bis(o-iminobenzosemiquinonato)metal complexes (Cu, Ni,
      Pd). The art of establishing physical oxidation states in transition-metal
      complexes containing radical ligands.
AB  - The ligand 2-anilino-4,6-di-tert-butylphenol and its 2-(3,5-dichloroanilino)-4,6
      di-tert-butylphenol analogue react in CH(3)CN or CH(3)OH solutions with divalent
      transition metal ions in the presence of air and triethylamine. Depending on the
      metal:ligand ratio (1:1, 1:2, or 1:3) and the presence (or absence) of the cyclic
      amine 1,4-dimethyl-1,4,7-triazacyclononane (dmtacn), the following complexes have
      been isolated as crystalline solids: [Co(III)(L(ISQ))(3)] (1);
      [Cu(II)(dmtacn)(L(ISQ))]PF(6) (2); [Cu(II)(L(ISQ))(2)] (3); [Ni(II)(L(ISQ))(2)]
      (4a); [Ni(II)((Cl)L(ISQ))(2)] (4b); [Pd(II)(L(ISQ))(2)] (5). (L(ISQ))(-)
      represents the monoanionic o-iminobenzosemiquinonate radical (S(rad) = (1)/(2)).
      Compounds 1-5 have been characterized by single-crystal X-ray crystallography at
      100(2) K. For all complexes it is unambiguously established that the O,N
      coordinated o-iminobenzosemiquinonato(1-) ligand is present. Complexes 3, 4b, and
      5 are square planar molecules which possess an S(t) = (1)/(2), 0, and 0 ground
      state, respectively, as was established by (1)H NMR and EPR spectroscopies and
      variable-temperature magnetic susceptibility measurements. Complex 2 possesses an
      S(t) = 1 ground state which is attained via strong intramolecular ferromagnetic
      coupling (J = +195 cm(-1)) between the d(x)2-(y)2 magnetic orbital of the Cu(II)
      ion and the pi-orbital of the ligand radical. Complex 1 contains three mutually
      orthogonal (L(ISQ))(-*) ligands and has an S(t) = (3)/(2) ground state. It is
      shown that the electronic structure of 4a and 5 is adequately described as
      singlet diradical containing a divalent, diamagnetic d(8) configurated central
      metal ion and two strongly antiferromagnetically coupled (L(ISQ))(-) radical
      ligands. It is concluded that the same electronic structure prevails in the
      classic bis(o-diiminobenzosemiquinonato)- and bis(o-benzosemiquinonato)metal
      complexes of Ni(II), Pd(II), and Pt(II). The electrochemistry of all complexes
      has been investigated in detail. For 3, 4a, and 5 a series of reversible one
      electron-transfer waves leads to the formation of the anions and cations
      [M(L)(2)](2-),(1-),(1+),(2+) which have been characterized
      spectroelectrochemically. All redox processes are shown to be ligand-based.

PMID- 11456868
TI  - The chemical nature of surface point defects on MoO3(010): adsorption of hydrogen
      and methyl.
AB  - We report density functional theory calculations using the Adaptive Coordinate
      Real-space Electronic Structure (ACRES) method of the terminal oxygen vacancy on
      the (010) surface of MoO3, within a (2 x 2) ordered array of vacancies on the
      surface. Analysis of the electronic structure of this surface shows that there
      are unoccupied dangling d(xz) and d(z)2 orbitals perpendicular to the surface
      that are created by the removal of terminal oxygen. The Mo-oxygen bonds
      surrounding the vacancy contract; however, the overall morphology of the surface
      is not drastically distorted. The vacancies alter the chemical character of the
      surface, as shown by studies of hydrogen and methyl binding. On both the
      "perfect" and vacancy surfaces, hydrogen was most strongly adsorbed over the
      terminal oxygen and most weakly bound over the symmetric bridging oxygen.
      Hydrogen is bound over the Mo atom, with a slightly smaller binding energy than
      hydrogen over the asymmetric bridging oxygen. The most favorable binding site for
      methyl on the vacancy surface is over the Mo atom exposed by removal of a
      terminal oxygen, whereas methyl bound to terminal oxygen is most stable on the
      perfect surface. There is no local minimum for adsorption over the symmetric
      bridging oxygen; instead, a methyl placed over this site moves toward the
      terminal oxygen vacancy. Analysis of the bonding shows that methyl is bound more
      strongly than hydrogen over the Mo atom because the C 2p orbital has better
      overlap with the Mo d(z)2 orbital than the hydrogen 1s. In addition, the steric
      repulsion observed for methyl over the perfect MoO3(010) surface is more easily
      relieved with the presence of the terminal oxygen vacancy.

PMID- 11456869
TI  - Magnetic susceptibility tensor and heme contact shifts determinations in the
      Rhodobacter capsulatus ferricytochrome c': NMR and magnetic susceptibility
      studies.
AB  - The 1H and 15N resonances of the carbon monoxide complex of ferrocytochrome c' of
      Rhodobacter capsulatus, a ferrous diamagnetic heme protein, have been extensively
      assigned by TOCSY-HSQC, NOESY-HSQC, and HSQC-NOESY-HSQC 3D heteronuclear
      experiments performed on a 7 mM sample labeled with 15N. Based on short-range and
      medium-range NOEs and H(N) exchange rates, the secondary structure consists of
      four helices: helix 1 (3-29), helix 2 (33-48), helix 3 (78-101), and helix 4 (103
      125). The 15N, 1HN, and 1H(alpha) chemical shifts of the CO complex form are
      compared to those of the previously assigned oxidized (or ferric) state. From the
      chemical shift differences between these redox states, the orientation and the
      anisotropy of the paramagnetic susceptibility tensor have been determined using
      the crystallographic coordinates of the ferric state. The chi-tensor is axial,
      and the orientation of the z-axis is approximately perpendicular to the heme
      plane. The paramagnetic chemical shifts of the protons of the heme ligand have
      been determined and decomposed into the Fermi shift and dipolar shift
      contributions. Magnetic susceptibility studies in frozen solutions have been
      performed. Fits of the susceptibility data using the model of Maltempo (Maltempo,
      M. M. J. Chem. Phys. 1974, 61, 2540-2547) are consistent with a rather low
      contribution of the S = 3/2 spin state over the range of temperatures and confirm
      the value of the axial anisotropy. Values in the range 10.4-12.5 cm(-1) have been
      inferred for the axial zero-field splitting parameter (D). Analysis of the
      contact shift and the susceptibility data suggests that cytochrome c' of Rb.
      capsulatus exhibits a predominant high-spin character of the iron in the oxidized
      state at room temperature.

PMID- 11456870
TI  - Application of ab initio molecular dynamics for a priori elucidation of the
      mechanism in unimolecular decomposition: the case of 5-nitro-2,4-dihydro-3H-1,2,4
      triazol-3-one (NTO).
AB  - We have tested a new and general approach for the theoretical study of
      unimolecular decomposition. By combining the power of the ab initio molecular
      dynamics (MD) and ab initio molecular orbital (MO) methods, our approach requires
      no prior experimental knowledge or intuitive assumptions about the decomposition.
      Instead, the reaction channels are first sampled theoretically by simulating a
      molecule at high temperature in a number of trajectories, using the density
      functional theory (DFT) based ab initio MD method with a planewave basis set and
      pseudopotentials. Each type of these channels is then further examined by well
      established ab initio MO method to locate the energy barrier and transition
      structure and to verify the ab initio MD results. The power of such an approach
      is demonstrated in a case study for the complicated unimolecular thermal
      decomposition of NTO (5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one), with several
      interesting new features uncovered. The C-NO2 homolysis is indeed the dominant
      channel at high temperature, while the departing NO2 could capture a H atom from
      the NTO ring to form HONO, by either a concerted bond breaking mechanism or by a
      bimolecular reaction between the NO2 group and the triazol ring. At lower
      temperature, the dissociation channels initiated by hydrogen migrations should be
      activated first. The channel with hydrogen migration followed by ring opening and
      then by HONO loss has an energy barrier of 38.0 kcal/mol at the rate-determining
      step, being the lowest among all the investigated dissociation paths and much
      lower than previously thought. The energy barrier for nitro-nitrite rearrangement
      is lower than that for the C-NO2 homolysis but makes only a minor contribution
      due to the entropy factor. And the NTO ring could rupture in the two C-N bonds
      connected to the carbonyl carbon, and the energy barriers for such processes are
      only 2-4 kcal/mol higher than that for the C-NO2 homolysis.

PMID- 11456871
TI  - Hindered inversion of chiral ion-dipole pairs.
AB  - O-Protonated S-(-)-1-phenyl-1-methoxyethane (IS) has been generated in the gas
      phase by CH3(2)Cl+ methylation of S-(-)-1-phenylethanol (1S). Detailed
      information on the reorganization dynamics of the intimate ion-dipole pair (IIS),
      arising from IS by C-O bond dissociation, is inferred from the kinetic study of
      the intramolecular inversion of configuration of IS vs its dissociation to alpha
      methylbenzyl cation (III) and CH(3)OH. The behavior of IIS in the gas phase is
      compared to that observed in aqueous solutions, where the loss of optical
      activity of IS is prevented by exchange of the leaving CH3OH with the solvent
      shell. Hindered inversion of IS in solution is attributed to the operation of
      attractive interactions between the moving CH3OH moiety and the solvent cage
      which inhibit internal return in the intimate ion-dipole pair IIS. Similar
      interactions do not operate in the solvolysis of 18O-labeled 1S in aqueous acids,
      whose loss of optical activity efficiently competes with exchange of the leaving
      H2(18)O with the solvent shell.

PMID- 11456872
TI  - Triplet organometallic reactivity under ambient conditions: an ultrafast UV
      pump/IR probe study.
AB  - The reactivity of triplet 16-electron organometallic species has been studied in
      room-temperature solution using femtosecond UV pump IR probe spectroscopy.
      Specifically, the Si-H bond-activation reaction of photogenerated triplet
      Fe(CO)(4) and triplet CpCo(CO) with triethylsilane has been characterized and
      compared to the known singlet species CpRh(CO). The intermediates observed were
      studied using density functional theory (DFT) as well as ab initio quantum
      chemical calculations. The triplet organometallics have a greater overall
      reactivity than singlet species due to a change in the Si-H activation mechanism,
      which is due to the fact that triplet intermediates coordinate weakly at best
      with the ethyl groups of triethylsilane. Consequently, the triplet species do not
      become trapped in alkyl-solvated intermediate states. The experimental results
      are compared to the theoretical calculations, which qualitatively reproduce the
      trends in the data.

PMID- 11456873
TI  - Energy distribution and redistribution and chemical reactivity. The generalized
      delta overlap-density method for ground state and electron transfer reactions: a
      new quantitative counterpart of electron-pushing.
AB  - A new approach to prediction of organic reactions and understanding of the
      electron flow involved in the reaction mechanisms is presented. The method
      developed permits comparison of electronic structures of species different in
      multiplicity, charge, and geometry based on use of spin- and charge-independent
      entities-"overlap corrected density matrices". The method utilizes the basis
      orbitals of one molecule A (e.g. reactant) in the computation of a second
      molecule, B, derived from the first by an approach to product. This then provides
      two Overlap-Density Matrices with a common set of basis (e.g. hybrid) orbitals.
      Subtraction of Overlap-Density Matrix B from Matrix A affords the Delta Overlap
      Density Matrix. Each element of the Delta Overlap-Density matrix gives the change
      in electron population of a bond or of a single hybrid orbital. Molecule B may
      differ from A by the addition or loss of an electron, by stretching of a bond, by
      electronic excitation, or by some other perturbation. The Delta Overlap-Density
      matrices afford a detailed description of the reaction process and provide
      predictions of overall reactions including such subtleties as regiochemistry.

PMID- 11456874
TI  - Chemical nucleation for CVD diamond growth.
AB  - A new nucleation method to form diamond by chemically pretreating silicon (111)
      surfaces is reported. The nucleation consists of binding covalently 2,2
      divinyladamantane molecules on the silicon substrate. Then low-pressure diamond
      growth was performed for 2 h via microwave plasma CVD in a tubular deposition
      system. The resulting diamond layers presented a good cristallinity and the Raman
      spectra showed a single very sharp peak at 1331 cm(-1), indicating high-quality
      diamonds.

PMID- 11456875
TI  - Reactivity of site-isolated metal clusters: propylidyne on gamma-Al2O3-supported
      Ir4.
AB  - To contrast the reactivity of supported metal clusters with that of extended
      metal surfaces, we investigated the reactions of tetrairidium clusters supported
      on porous gamma-Al2O3 (Ir4/gamma-Al2O3) with propene and with H2. Infrared, 13C
      NMR, and extended X-ray absorption fine-structure spectroscopy were used to
      characterize the ligands formed on the clusters. Propene adsorption onto
      Ir4/gamma-Al2O3 at 298 K gave stable, cluster-bound mu3-propylidyne. Propene
      adsorbed onto Ir4/gamma-Al2O3 at 138 K reacted at approximately 219 K to form a
      stable, highly dehydrogenated, cluster-bound hydrocarbon species approximated as
      CxHy (such as, for example, C3H2 or C2H). H2 reacted with Ir4/gamma-Al2O3 at 298
      K, forming ligands (likely hydrides), which prevented subsequent reaction of the
      clusters with propene to form propylidyne. Propylidyne on Ir4 was stable in
      helium or H2 as the sample was heated to 523 K, whereupon it reacted with oxygen
      of the support to give CO. Propylidyne on Ir4 did not undergo isotopic exchange
      in the presence of D2 at 298 K. In contrast, the literature shows that
      propylidyne chemisorbed on extended metal surfaces is hydrogenated in the
      presence of H2 (or D2) and exchanges hydrogen with gaseous D2 at room
      temperature; in the absence of H2, it decomposes thermally to give hydrocarbon
      fragments at temperatures much less than 523 K. The striking difference in
      reactivities of propylidyne on clusters and propylidyne on extended metal
      surfaces implies the requirement of ensembles of more than the three metal
      surface atoms bonded to propylidyne in the surface reactions. The results
      highlight the unique reactivity of small site-isolated metal clusters.

PMID- 11456876
TI  - Triosephosphate isomerase: a theoretical comparison of alternative pathways.
AB  - Three mechanisms proposed for the triosephosphate isomerase (TIM) catalyzed
      reactions were studied with the QM/MM approach using B3LYP/6-31+G(d,p) as the QM
      method. The two pathways that involve an enediol species were found to give
      similar values for the barriers and the calculated rates are in satisfactory
      agreement with experiment. By contrast, the mechanism that involves
      intramolecular proton transfer in the enediolate was found to be energetically
      unfavorable due to electrostatic interactions with His 95, a conserved residue in
      TIM from different organisms. A perturbation analysis was used to determine the
      residues that make the major contribution to catalysis.

PMID- 11456877
TI  - Polymorphism in 2,4,6-trinitrotoluene crystallized from solution.
AB  - An examination has been made of the role of solvent type in the definition of the
      polymorphic nature of 2,4,6-trinitrotoluene precipitated from solution. A
      combination of calorimetric and structural techniques including in situ
      crystallization studies using synchrotron radiation has shown that the variations
      in polymorphic form following precipitation from solution do not arise
      specifically from any stereospecific guidance that the nature of the solvent
      might impose on the structural form. Rather the differences are linked to the
      variations in solubility and hence supersaturation which might build up prior to
      nucleation and growth and to the isolation of the metastable orthorhombic phase
      from the solvent. The final conclusion is that the changes fit well with
      Ostwald's Law of Stages with the orthorhombic form always precipitating initially
      followed by its conversion to the stable monoclinic form. The previously observed
      tendency for some solvents to yield one or the other form then becomes
      attributable to kinetics in solution rather than structural control. It can be
      associated with the solubility of the material in the solvent used and the role
      of this factor in a solvent-mediated phase transformation. On this basis rules
      can be formulated for the isolation of the metastable forms of this and similarly
      related polymorphic systems.

PMID- 11456878
TI  - Soluble electroluminescent poly(phenylene vinylene)s with balanced electron- and
      hole injections.
AB  - We report a new route for the design of efficient soluble electroluminescent PPV
      based copolymers bearing electron-deficient oxadiazole (OXD) moieties on side
      chains. The introduction of OXD through a long alkylene spacer with PPV backbone
      provides a molecular dispersion of OXD in the film; both the side chain OXD and
      the main chain PPV do retain their own electron-transport and emissive
      properties, respectively. The use of phenylene vinylene derivatives with
      asymmetric and branched substituents and a long spacer provides solubility for
      ease of device fabrication as well as amorphous structure to allow a well-mixing
      of OXD groups with the main chains. By properly adjusting the OXD content through
      copolymerization, we can tailor the chemical structure of electroluminescent
      material to give a balance of hole- and electron injections for various metal
      cathodes, such that the quantum efficiency is significantly improved and the turn
      on voltage is reduced for the devices with aluminum and calcium. For the device
      with calcium fabricated in open air, a maximum brightness of 15000 cd/m(2) at 15
      V/100 nm and a maximum luminance efficiency of 2.27 cd/A can be obtained,
      respectively, about 30 times brighter and 9.4 times more efficient than those
      with the corresponding homopolymer, poly[2-methoxy-5-(2'-ethylhexyloxy)-p
      phenylenevinylene] (MEH-PPV). The use of physical blends to simulate the
      copolymers provides no significant improvement, since phase-separation structures
      appear, causing an inefficient utilization of OXD and sometimes voltage-dependent
      emission spectra. The present route permits a fabrication of single layer PLED
      with high brightness, high efficiency, and low turn-on voltage.

PMID- 11456879
TI  - Effects of substituting a OH group by a F atom in D-glucose. Ab initio and DFT
      analysis.
AB  - High-level ab initio and DFT methods up to MP2/6-311++G//B3LYP/6-31G and B3LYP/6
      311++G//B3LYP/6-31G levels have been used to assess the relative energies of 17
      different structures of D-glucose and 13 different structures of 4-deoxy-4-fluoro
      D-glucose. The structures were confirmed to correspond to minima on the potential
      energy surface at the RHF/6-31G level. Solvation Model 5.4/AM1 was used to
      calculate the effects of aqueous solution. The substitution of a OH group by a F
      atom does not much change the shape and electrostatic potential around
      corresponding conformers, but in the gas phase it destabilizes the cooperative
      network of intramolecular hydrogen bonds. This destabilization mostly affects
      structures with a chain of intramolecular hydrogen bonds oriented
      counterclockwise, as fluorine is unable to donate a hydrogen bond and therefore
      causes a gap in the chain. In contrast, for clockwise-oriented networks of
      hydrogen bonds, the fluorine can act as an acceptor at the end of a chain of
      cooperative hydrogen bonds. A slightly higher energy of anomeric and exo-anomeric
      stabilization is another effect of substituting the fourth hydroxyl group by a
      fluorine atom in D-glucose, observed both in the gas phase and in aqueous
      solution. For this reason, the alpha anomers contribute more to the equilibrium
      population of structures of 4-deoxy-4-fluoro-D-glucose than D-glucose. In aqueous
      solution, both D-glucose and its 4-deoxy-4-fluoro analogue are present as a
      mixture of mainly three corresponding structures. This indicates that 4-deoxy-4
      fluoro-D-glucose is a good substitute for D-glucose in terms of its biochemical
      and biological activity. Moreover, this suggests that, for molecules with limited
      conformational freedom, the substitution of a OH group by a F atom is very likely
      to lead to a potential new drug. In contrast, it had already been shown that, for
      conformationally labile aliphatic compounds, replacement of a hydroxyl by a
      fluorine increases conformational diversity, so the fluorine-containing aliphatic
      molecules were not likely to be an example of a successful drug design. On the
      other hand, this work shows that, among molecules with limited conformational
      freedom, such as cyclic compounds, one is very likely to find targets for a
      successful rational drug design.

PMID- 11456880
TI  - Electron-rich bonding and the importance of s,p mixing as one moves across a
      period: a lesson from the LiSn system.
AB  - The electronic structure of an unusual LiSn phase (computed using band structure
      calculations in the framework of the extended Huckel tight binding theory) is the
      starting point for a general analysis of the variation of electron-rich
      multicenter bonding across a period. The LiSn crystal structure of Muller and
      Schafer in question contains 2D slabs of Sn atoms arranged as microscopic stairs
      and intercalated by Li atoms. Discrepancies between an electron count derived
      from a recent extension of the Zintl-Klemm rules to electron-rich systems (5(2/3)
      electrons) and the experimental one (5 electrons for the Sn sublattice) and other
      failures of chemical "common sense" emerge in the analysis. The key for
      interpretation of a series of puzzling results was found in the comparative
      analysis of the Sn net with other main group element hypervalent slabs.
      Increasing s,p-mixing as one moves from the right to the left side of the same
      row of the periodic table is responsible for these effects. The result is that a
      lower electron count is found in the Sn slabs relative to the one expected from
      the extended Zintl-Klemm theory. The effect should also occur in discrete
      molecules. We also showed that the Li atoms have a role in the determination of
      the final structure, not only because of their small size but also through the
      degree of the electron transfer to the Sn sublattice.

PMID- 11456881
TI  - Nucleophilic substitution at the imidoyl carbon atom: intermediate mechanistic
      and reactivity behavior between carbonyl and vinyl carbon substitution.
AB  - Gas-phase nucleophilic substitution reactions at the imidoyl carbon have been
      investigated using chloride exchanges, Cl- + RY=CHCl right harpoon over left
      harpoon RY=CHCl + Cl- with Y = N and R = F, H or CH3, at the MP2, B3LYP and G2(+)
      levels using the MP2/6-311+G geometries. The results are compared with those for
      the vinyl (Y = CH) and carbonyl (Y = O) carbon substitution. The mechanism and
      reactivity of substitution at the imidoyl carbon are intermediate between those
      of carbonyl (SNpi) and vinyl carbon (SNsigma) substitution, which is directly
      related to the electronegativity of Y, CH < N < O. The prediction of competitive
      SNsigma with SNpi path for the imidoyl chloride is consistent with the S(N)1-like
      mechanism proposed for reactions in solution. The important factors in favor of
      an in-plane concerted SN2 (SNsigma) over an out-of-plane pi-attack (SNpi) path
      are (i) lower proximate sigma-sigma* charge-transfer energies (DeltaECT), (ii)
      stronger electrostatic stabilization (DeltaENCT), and (iii) larger lobe size on
      C(alpha) for the sigma*- than pi*-LUMO despite the higher sigma* than pi* level.
      The electron correlation energy effects at the MP2 level are overestimated for
      the relatively delocalized structure (S(N)pi TS) but are underestimated for the
      localized structure (SNsigma TS) so that the MP2 energies lead to a wrong
      prediction of preferred reaction path for the vinyl chloride. The DFT at the
      B3LYP level predicts correct reaction pathways but overestimates the electron
      correlation effects.

PMID- 11456882
TI  - Deconvolution and assignment of different optical transitions of the blue copper
      protein azurin from optically detected electron paramagnetic resonance
      spectroscopy.
AB  - Magnetic circular dichroism is a powerful spectroscopic tool for the assignment
      of optical resonance lines. An extension of this technique, microwave-modulated
      circular dichroism, provides additional details, in particular information about
      the orientation of optical transition moments. It arises from magnetization
      precessing around the static magnetic field, excited by a microwave field, in
      close analogy to electron paramagnetic resonance (EPR). In this paper we
      investigate the visible and near-infrared spectrum of the blue copper protein
      Pseudomonas aeruginosa azurin. Using a nonoriented sample (frozen solution), we
      apply this technique to measure the variation of the optical anisotropy with the
      wavelength. A comparison with the optical anisotropies of the possible ligand
      field and charge-transfer transitions allows us to identify individual resonance
      lines in the strongly overlapping spectrum and assign them to specific electronic
      transitions. The technique is readily applicable to other proteins with
      transition metal centers.

PMID- 11456883
TI  - The intrinsic stability of the noble gas-coordinated transition-metal complex
      ions.
AB  - Density-functional-theory and high-level ab initio calculations have been
      performed on the [AuXe4]2+ ion and some other hypothetical xenon-, krypton-, and
      argon-coordinated transition-metal complex cations in the gas phase. Geometry
      optimization at the QCISD(T) level using a (6s7p4d2f1g) basis set for Au and a
      (4s4p2d1f) set for Xe predicted Au-Xe bond lengths in good agreement with the
      AuXe4(2+)(Sb2F11-)2 crystal structure. The ligand-binding energies of the
      [AuXe4]2+, [AuXe4]3+, and [PtXe4]2+ ions were predicted to be 229, 565, and 233
      kcal/mol, respectively, at the CCSD(T) level. It is found that higher-level
      correlation effects are important to obtain accurate geometry parameters. The
      calculated results also indicated that various trivalent, tetravalent, and
      hexavalent transition-metal complexes of xenon or krypton might also be
      intrinsically stable.

PMID- 11456884
TI  - Ab initio study of the atmospheric oxidation of CS2.
AB  - The reactions of OH with CS2, OCS, and 3SO and of 3O2 with CS2, SCSOH, and HOSO
      have been studied by optimizing minima and transition states with B3LYP/6-31+G(d)
      and carrying out higher-level ab initio calculations on fixed geometries. The
      combined calculations provide valuable insight into the mechanism for the
      atmospheric oxidation of CS2. The initial step is the formation of the SCSOH
      complex (1) which readily adds molecular oxygen to form the SC(OO)SOH complex
      (8). A key step is the oxygen atom transfer to the sulfur bearing the hydroxyl
      group which leads directly to OCS plus HOSO. The HOSO + 3O2 reaction has a near
      zero calculated activation barrier so generation of O2H + SO2 should proceed
      readily in the atmosphere.

PMID- 11456885
TI  - Size-dependent optical spectroscopy of a homologous series of CdSe cluster
      molecules.
AB  - The optical properties and electronic structure of a homologous series of CdSe
      cluster molecules covering a size range between 0.7 and 2 nm are investigated.
      CdSe cluster molecules with 4, 8 10, 17, and 32 Cd atoms, capped by selenophenol
      ligands, were crystallized from solution and their structures determined by
      single-crystal X-ray diffraction. The cluster molecules are composed of a
      combination of adamanthane and barylene-like cages, the building blocks of the
      zinc blende and the wurtzite structures of the bulk CdSe. The onset of the room
      temperature absorption and low-temperature photoluminescence excitation spectra
      exhibit a systematic blue shift with reduced cluster size manifesting the quantum
      confinement effect down to the molecular limit of the bulk semiconductor. Blue
      green emission, shifted substantially to lower energy from the absorption onset,
      is observed only at low temperature and its position is nearly independent of
      cluster size. The wavelength dependence of both photoluminescence and
      photoluminescence excitation was measured. The emission is assigned to forbidden
      transitions involving the cluster-molecule surface-capping ligands. This
      assignment is supported by the emission decay which exhibits distributed kinetics
      with microsecond time scale. The temperature dependence of the emission intensity
      is quantitatively explained by multiphonon-induced nonradiative relaxation
      mediated by low-frequency vibrations of the selenophenol capping ligands. Upon
      irradiation, the emission of all cluster molecules is quenched. Warming up and
      recooling leads to recovery of the emission (partial or complete) for all but the
      cluster molecule with 10 Cd atoms. This temporary darkening is assigned to the
      photoinduced charging of the cluster-molecule surface ligands, resembling the
      reversible on-off blinking of the emission observed for larger CdSe nanocrystals.

PMID- 11456886
TI  - Allylic alcohol epoxidation by methyltrioxorhenium: a density functional study on
      the mechanism and the role of hydrogen bonding.
AB  - By locating all relevant transition structures with a hybrid density functional
      method, we explored the three most reasonable mechanisms for H2O2 epoxidation of
      propenol catalyzed by methyltrioxorhenium (MTO), namely: (i) coordination of
      propenol as lone pair donor to rhenium mono- and bis-peroxo complexes followed by
      intramolecular epoxidation, (ii) formation of a metal alcoholate, derived from
      addition of propenol to the Re complex with the formation of a metal-OR bond,
      followed by intramolecular epoxidation, (iii) intermolecular oxygen transfer
      assisted by hydrogen bonding where the rhenium complex acts as hydrogen bond
      acceptor and HOR as hydrogen bond donor. The computational results demonstrate
      that the last route is highly favored over the other two and, in particular, they
      provide the first unambiguous and compelling evidence that alcoholate-metal
      complexes, mechanism (ii), do not appreciably contribute to product formation. In
      keeping with experimental findings, theoretical data predict that the monoperoxo
      Re complex should be considerably less reactive than its bis(peroxo) counterpart
      and suggest that the hydrated form of the latter complex should be the actual
      active epoxidant species. All transition structures exhibit a distorted spiro
      like structure, while the most stable ones feature hydrogen bonding to the
      attacking peroxo fragment with the olefinic OH group either in an "outside"
      (OC1C2C3 approximately 128 degrees ) or "inside" (OC1C2C3 approximately 14
      degrees ) conformation. Previous qualitative models for transition structures of
      Re-catalyzed epoxidation of allylic alcohols are discussed in the light of our
      computational data.

PMID- 11456887
TI  - Electron-transfer-induced tautomerization in methylindanones: electronic control
      of the tunneling rate for enolization.
AB  - The radical cations generated from 4-methyl- and 4,7-dimethylindanone, as well as
      their deuterated isotopomers, isolated in Argon matrices, were found to undergo
      enolization to the corresponding enol radical cations at rates that differ by
      orders of magnitude. It is shown by quantum chemical calculations that the effect
      of the remote methyl group in the 4-position is of purely electronic nature in
      that it stabilizes the unreactive pi-radical relative to the reactive sigma
      radical state of the 7-methylindanone radical cation. The observed kinetic
      behavior of the two compounds can be reproduced satisfactorily on the basis of
      calculated height and width of the thermal barrier for enolization, using the
      Bell model for quantum mechanical tunneling. High-level calculations on the
      methylacrolein radical cation show that barriers for enolization in radical
      cations are overestimated by B3LYP/6-31G.

PMID- 11456888
TI  - Transient UV Raman spectroscopy finds no crossing barrier between the peptide
      alpha-helix and fully random coil conformation.
AB  - Transient UV resonance Raman measurements excited within the amide pi --> pi
      transitions of a 21 unit alpha-helical peptide has for the first time determined
      a lower bound for the unfolding rate of the last alpha-helical turn to form a
      fully random coil peptide. A 3 ns T-jump is generated with 1.9 microm laser
      pulses, which are absorbed by water. Subsequent 3 ns 204 nm UV pulses excite the
      amide Raman spectra at delay times between 3 ns and 1 ms, to monitor the peptide
      conformational evolution. We find approximately 180 ns relaxation times which
      result in a rate constant of >5 x 10(6) s(-1) for unfolding of the last alpha
      helical turn. Our data are inconsistent with slow alpha-helix nuclei melting.

PMID- 11456889
TI  - The beta-peptide hairpin in solution: conformational study of a beta-hexapeptide
      in methanol by NMR spectroscopy and MD simulation.
AB  - The structural and thermodynamic properties of a 6-residue beta-peptide that was
      designed to form a hairpin conformation have been studied by NMR spectroscopy and
      MD simulation in methanol solution. The predicted hairpin would be characterized
      by a 10-membered hydrogen-bonded turn involving residues 3 and 4, and two
      extended antiparallel strands. The interproton distances and backbone torsional
      dihedral angles derived from the NMR experiments at room temperature are in
      general terms compatible with the hairpin conformation. Two trajectories of
      system configurations from 100-ns molecular-dynamics simulations of the peptide
      in solution at 298 and 340 K have been analyzed. In both simulations reversible
      folding to the hairpin conformation is observed. Interestingly, there is a
      significant conformational overlap between the unfolded state of the peptide at
      each of the temperatures. As already observed in previous studies of peptide
      folding, the unfolded state is composed of a (relatively) small number of
      predominant conformers and in this case lacks any type of secondary-structure
      element. The trajectories provide an excellent ground for the interpretation of
      the NMR-derived data in terms of ensemble averages and distributions as opposed
      to single-conformation interpretations. From this perspective, a relative
      population of the hairpin conformation of 20% to 30% would suffice to explain the
      NMR-derived data. Surprisingly, however, the ensemble of structures from the
      simulation at 340 K reproduces more accurately the NMR-derived data than the
      ensemble from the simulation at 298 K, a question that needs further
      investigation.

PMID- 11456890
TI  - The first solution structure of a paramagnetic copper(II) protein: the case of
      oxidized plastocyanin from the cyanobacterium Synechocystis PCC6803.
AB  - The NMR solution structure of oxidized plastocyanin from the cyanobacterium
      Synechocystis PCC6803 is here reported. The protein contains paramagnetic
      copper(II), whose electronic relaxation times are quite unfavorable for NMR
      solution studies. The structure has been solved on the basis of 1041 meaningful
      NOESY cross-peaks, 18 1D NOEs, 26 T(1) values, 96 dihedral angle constraints, and
      18 H-bonds. The detection of broad hyperfine-shifted signals and their full
      assignment allowed the identification of the copper(II) ligands and the
      determination of the Cu-S-C-H dihedral angle for the coordinated cysteine. The
      global root-mean-square deviation from the mean structure for the solution
      structure family is 0.72 +/- 0.14 and 1.16 +/- 0.17 A for backbone and heavy
      atoms, respectively. The structure is overall quite satisfactory and represents a
      breakthrough, in that it includes paramagnetic copper proteins among the
      metalloproteins for which solution structures can be afforded. The comparison
      with the available X-ray structure of a triple mutant is also performed.

PMID- 11456891
TI  - Microstructure determination of AOT + phenol organogels utilizing small-angle X
      ray scattering and atomic force microscopy.
AB  - Dry reverse micelles of the anionic twin-tailed surfactant bis(2-ethylhexyl)
      sulfosuccinate (AOT) dissolved in nonpolar solvents spontaneously form an
      organogel when p-chlorophenol is added in a 1:1 AOT:phenol molar ratio. The
      solvents used were benzene, toluene, m-xylene, 2,2,4-trimethylpentane
      (isooctane), decane, dodecane, tetradecane, hexadecane, and 2,6,10,14
      tetramethylpentadecane (TMPD). The proposed microstructure of the gel is based on
      strands of stacked phenols linked to AOT through hydrogen bonding. Small-angle X
      ray scattering (SAXS) spectra of the organogels suggest a characteristic length
      scale for these phenol-AOT strands that is independent of concentration but
      dependent on the chemical nature of the nonpolar solvent used. Correlation
      lengths determined from the SAXS spectra indicate that the strands self-assemble
      into fibers. Direct visualization of the gel in its native state is accomplished
      by using tapping mode atomic force microscopy (AFM). It is shown that these
      organogels consist of fiber bundle assemblies. The SAXS and AFM data reinforce
      the theory of a molecular architecture consisting of three length scales
      AOT/phenolic strands (ca. 2 nm in diameter) that self-assemble into fibers (ca.
      10 nm in diameter), which then aggregate into fiber bundles (ca. 20-100 nm in
      diameter) and form the organogel.

PMID- 11456892
TI  - Formation of alkanethiol monolayer on Ge(111).
AB  - Alkanethiols, CH3(CH2)(n-1)SH, are shown to react readily with HF-treated Ge(111)
      surface at room temperature to form a high-quality monolayer. The resulting films
      are characterized by using contact angle analysis (CAA), atomic force microscopy
      (AFM), X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (SE),
      and high-resolution electron energy loss spectroscopy (HREELS). The octanethiol
      and octadecanethiol films on Ge(111) both exhibit 101 degrees and 40 degrees
      water and hexadecane contact angles, respectively. These values indicate that the
      thiol surface coverage is relatively high, and that the films possess a high
      degree of orientational ordering. The angle-resolved XPS analysis supports that
      thiols are bound to the Ge surface by Ge-S bonds at the monolayer/Ge interface.
      The film thickness values obtained by XPS and SE agree well with the earlier
      reported values on alkyl monolayers on Ge(111) prepared by Grignard reaction. On
      the basis of HREEL spectra taken after thermal annealing steps, the monolayers
      are found to be thermally stable up to 450 K. The thermal stability provides
      further evidence that thiols are covalently bonded to Ge(111).

PMID- 11456893
TI  - Direct observation of protein vibrations by selective incorporation of
      spectroscopically observable carbon-deuterium bonds in cytochrome c.

PMID- 11456894
TI  - Parallel kinetic resolution under catalytic conditions: a three-phase system
      allows selective reagent activation using two catalysts.

PMID- 11456895
TI  - Ab initio study of the carbon-to-carbon identity proton transfer from ketene to
      its anion in the gas phase.

PMID- 11456896
TI  - Phototriggered Ru(II)-dimethylsulfoxide linkage isomerization in crystals and
      films.

PMID- 11456897
TI  - A highly fluorescent DNA base analogue that forms Watson-Crick base pairs with
      guanine.

PMID- 11456898
TI  - Lanthanide tags for time-resolved luminescence microscopy displaying improved
      stability and optical properties.

PMID- 11456899
TI  - Organic-inorganic composites comprised of ordered stacks of amphiphilic molecular
      disks.

PMID- 11456900
TI  - Ultrafast molecular logic gate based on optical switching between two long-lived
      radical ion pair states.

PMID- 11456901
TI  - Rhodium(I)-catalyzed homologation of aromatic aldehydes with
      trimethylsilyldiazomethane.

PMID- 11456902
TI  - Remote intermolecular "heavy-atom effect": spin-orbit coupling across the wall of
      a hemicarcerand.

PMID- 11456903
TI  - High-resolution macromolecular NMR spectroscopy inside living cells.

PMID- 11456904
TI  - Design of a new cascade reaction for the construction of complex acyclic
      architecture: the tandem acyl-claisen rearrangement.

PMID- 11456905
TI  - Formation of tetrahydrofuran from homoallylic alcohol via a tandem sequence: 2
      oxonia.

PMID- 11456906
TI  - Unusual temperature-dependent diastereoselectivity in the [2 + 2]
      photocycloaddition (Paterno-Buchi reaction) of benzophenone to cis- and trans
      cyclooctene through conformational control.

PMID- 11456907
TI  - Determination of the molecular electrical properties of self-assembled monolayers
      of compounds of interest in molecular electronics.

PMID- 11456908
TI  - Selective anion binding by a macrocycle with convergent hydrogen bonding
      functionality.

PMID- 11456909
TI  - Cysteine thiolate coordination in the ferrous CO complex of an engineered
      cytochrome b562.

PMID- 11456910
TI  - Cationic hyperbranched poly(amino ester): a novel class of DNA condensing
      molecule with cationic surface, biodegradable three-dimensional structure, and
      tertiary amine groups in the interior.

PMID- 11456911
TI  - Left or right, it is a matter of one methylene unit.

PMID- 11456912
TI  - Characterization of new six-membered transition states of the amino-alcohol
      promoted addition of dialkyl zinc to aldehydes.

PMID- 11456913
TI  - Direct catalytic asymmetric aldol reaction: synthesis of either syn- or anti
      alpha,beta-dihydroxy ketones.

PMID- 11456914
TI  - Recognition of nine base pairs in the minor groove of DNA by a tripyrrole peptide
      Hoechst conjugate.
AB  - A tripyrrole peptide-Hoechst conjugate (FPH-1) has been designed which recognizes
      nine dA/dT base pair A/T rich dsDNA sequences at subnanomolar concentrations and
      complexes its targets at near diffusion controlled rates to form a fluorescent
      product. Spectrofluorometric titrations show the stoichiometry of the complex to
      be (FPH-1)(2):dsDNA. Spectrofluorometric titrations were also employed to
      determine the product of the equilibrium constant for complexation (K(1)K(2)) of
      dsDNA by two FPH-1 molecules for 35 different oligomeric duplexes. Single base
      pair mismatches in the FPH-1 binding site were found to cause significant
      decreases in K(1)K(2) of 18- to 2300-fold. Thermal denaturation experiments
      provided similar results. Arguments are presented which favor the structure of
      the (FPH-1)(2):dsDNA minor groove complex to involve the two FPH-1 molecules in a
      slightly staggered, side-by-side, and antiparallel arrangement such that the bis
      benzimidazole moiety of one FPH-1 molecule lies adjacent to the tripyrrole moiety
      of the second FPH-1 molecule.

PMID- 11456915
TI  - Oxidation-active flavin models: oxidation of alpha-hydroxy acids by benzo
      dipteridine bearing metal-binding site in the presence of divalent metal ion and
      base in organic solvents.
AB  - The oxidizing ability of benzo-dipteridine bearing a bipyridin-6-ylmethyl moiety
      (4) was found to be increased with Zn(2+) by approximately 10(3)-fold for sulfite
      addition in MeOH and approximately 10(2)-fold for oxidation of an NADH model in
      MeCN. It was found for the first time that 4 is able to oxidize alpha-hydroxy
      acids to alpha-keto acids in the presence of a divalent metal ion such as Zn(2+),
      Co(2+), and Ni(2+) and an amine base in MeCN or t-BuOH, whereas benzo-dipteridine
      having a bipyridin-5-ylmethyl moiety (3) is unable to oxidize them under the same
      conditions. The oxidation reaction was kinetically investigated including the
      kinetic isotope effect for deuterated mandelic acids (k(H)/k(D) = 2.1-3.7) and
      the Hammett plots for substituted mandelic acids (V-shaped plots). In the
      reaction of alpha-substituted alpha-hydroxy acids such as alpha-methyl mandelic
      and benzylic acids with 4, novel oxidative decarboxylation was found to take
      place, giving acetophenone and benzophenone, respectively. The oxidation
      mechanism for mandelic acid was proposed to proceed via a ternary complex of
      4.Zn(2+).PhCH(OH)CO(2)(-), in which alpha-oxyanion of mandelate attacks C(4a)
      position of 4 to form an adduct followed by 1,2-elimination to afford benzoyl
      formate and 2e-reduced 4. The roles of the metal ion were proposed as follows;
      (i) activation of 4, (ii) substrate-binding site, and (iii) activation of the
      bound alpha-hydroxy acid by lowering pK(a)'s of alpha-OH and alpha-CH. This is a
      first example that a flavin model oxidizes alpha-hydroxy acids in the presence of
      a metal ion.

PMID- 11456916
TI  - Tandem ligation of unprotected peptides through thiaprolyl and cysteinyl bonds in
      water.
AB  - Tandem ligation for the synthesis and modification of proteins entails forming
      two or more regiospecific amide bonds of multiple free peptide segments without a
      protecting-group scheme. We here describe a semi-orthogonal strategy for ligating
      three unprotected peptide segments, two of which contain N-terminal (NT)
      cysteine, to form in tandem two amide bonds, an Xaa-SPro (thiaproline), and then
      an Xaa-Cys. This strategy exploits the strong preference of an NT-cysteinyl
      peptide under acidic conditions to undergo selectively an SPro-imine ligation
      rather than a Cys-thioester ligation. Operationally, it was performed in the N -
      > C direction, first by an imine ligation at pH < 3 to afford an Xaa-thiazolidine
      ester bond between a peptide containing a carboxyl terminal (CT)-glycoaldehyde
      ester and a second peptide containing both an NT-Cys and a CT-thioester. The
      newly created O-ester-linked segment with a CT-thioester was then ligated to
      another NT-cysteinyl peptide through thioester ligation at pH > 7 to form an Xaa
      Cys bond. Concurrently, this basic condition also catalyzed the O,N-acyl
      migration of an Xaa-thiazolidine ester to the Xaa-SPro bond at the first ligation
      site to complete the tandem three-segment ligation. Both ligation reactions were
      performed in aqueous buffered solvents. The effectiveness of this three-segment
      ligation strategy was tested in six peptides ranging from 19 to 70 amino acids,
      including thiaproline --> proline analogues of somatostatins and two CC
      chemokines. The thiaproline replacements in these peptides and proteins did not
      result in altered biological activity. By eliminating the protecting-group scheme
      and coupling reagents, tandem ligation of multiple free peptide segments in
      aqueous solutions enhances the scope of protein synthesis and may provide a
      useful approach for combinatorial segment synthesis.

PMID- 11456917
TI  - Precursor-directed biosynthesis of 16-membered macrolides by the erythromycin
      polyketide synthase.
AB  - Streptomyces coelicolor CH999/pJRJ2 harbors a plasmid encoding DEBS(KS1 degrees
      ), a mutant form of 6-deoxyerythronolide B synthase that is blocked in the
      formation of 6-deoxyerythronolide B (1, 6-dEB) due to a mutation in the active
      site of the ketosynthase (KS1) domain that normally catalyzes the first
      polyketide chain elongation step of 6-dEB biosynthesis. Administration of
      (2E,4S,5R)-2,4-dimethyl-5-hydroxy-2-heptenoic acid, N-acetylcysteamine thioester
      (6) an unsaturated triketide analogue of the natural triketide chain elongation
      intermediate to cultures of S. coelicolor CH999/pJRJ2 results in formation of a
      16-membered macrolactone, which is isolated in the hemiketal form 33. The
      formation of the octaketide 33 indicates that the triketide substrate has been
      processed by DEBS module 2 as if it were a diketide analogue. The substrate
      specificity of this novel reaction has been explored by the incubation of three
      additional analogues of the unsaturated triketide 6, compounds 18, 31, and 32,
      with S. coelicolor CH999/pJRJ2, resulting in the formation of the corresponding
      macrolactones 34, 35, and 36. By contrast, the unsaturated triketide 10, lacking
      a methyl group at C-2, did not give rise to any detectable macrolactone product
      when incubated with S. coelicolor CH999/pJRJ2.

PMID- 11456918
TI  - Terthienyl and poly-terthienyl ligands as redox-switchable hemilabile ligands for
      oxidation-state-dependent molecular uptake and release.
AB  - Mononuclear, dinuclear, and polymeric Ru(II) complexes formed from
      terthienylalkylphosphino redox-switchable hemilabile ligands demonstrate that
      this class of ligand provides electrochemical control over the electronic
      properties, coordination environments, and reactivities of bound transition
      metals. Specifically, [CpRuCO(kappa(2)-3'-(2-diphenylphosphinoethyl)-5,5' '
      dimethyl-2,2':5',2' '-terthiophene)][B(C(6)H(3)-3,5-(CF(3))(2))(4)] (4a) exhibits
      a 3 orders of magnitude increase in binding affinity for acetonitrile upon
      terthienyl-based oxidation. FT-IR spectroelectrochemical experiments on 4a
      indicate that terthienyl-based oxidation removes electron density from the metal
      center, equivalent to approximately 11-17% of the electronic change that occurs
      upon direct oxidation of Ru(II) to Ru(III) in analogous complexes. The
      spectroelectrochemical responses of 4a were compared to those of dimeric and
      polymeric analogues of 4a. The spectroelectrochemistry of the dimer is consistent
      with two sequential, one-electron ligand-based oxidations, compared to only one
      in 4a. In contrast, the polymer exhibits spectroelectrochemical behavior similar
      to that of 4a. The polymer spectroelectrochemistry shows changes in the metal
      center electronic properties between two different states, reflective of two
      discrete oxidation states of the polymeric ligand backbone. We propose that the
      polymer backbone does not allow one to vary the electronic properties of the
      metal center through a continuous range of oxidation states due to charge
      localization within the metalated films. In an effort to explore the molecular
      uptake and release properties of 4a and its polymer analogue as a function of
      ligand oxidation state, the oxidation-state-dependent coordination chemistries of
      4a and 4a(+)() with a variety of substrates were examined.

PMID- 11456919
TI  - Electrostatics of cell membrane recognition: structure and activity of neutral
      and cationic rigid push-pull rods in isoelectric, anionic, and polarized lipid
      bilayer membranes.
AB  - Design, synthesis, and structural and functional studies of rigid-rod ionophores
      of different axial electrostatic asymmetry are reported. The employed design
      strategy emphasized presence of (a) a rigid scaffold to minimize the
      conformational complexity, (b) a unimolecular ion-conducting pathway to minimize
      the suprastructural complexity and monitor the function, (c) an extended
      fluorophore to monitor structure, (d) variable axial rod dipole, and (e) variable
      terminal charges to create axial asymmetry. Studies in isoelectric, anionic, and
      polarized bilayer membranes confirmed a general increase in activity of uncharged
      rigid push-pull rods in polarized bilayers. The similarly increased activity of
      cationic rigid push-pull rods with an electrostatic asymmetry comparable to that
      of alpha-helical bee toxin melittin (positive charge near negative axial dipole
      terminus) is shown by fluorescence-depth quenching experiments to originate from
      the stabilization of transmembrane rod orientation by the membrane potential. The
      reduced activity of rigid push-pull rods having an electrostatic asymmetry
      comparable to that in alpha-helical natural antibiotics (a positive charge near
      the positive axial dipole terminus) is shown by structural studies to originate
      from rod "ejection" by membrane potentials comparable to that found in mammalian
      plasma membranes. This structural evidence for cell membrane recognition by
      asymmetric rods is unprecedented and of possible practical importance with regard
      to antibiotic resistance.

PMID- 11456920
TI  - An application of electronic asymmetry to highly enantioselective catalytic Diels
      Alder reactions.
AB  - The compounds (RRu)-[CyRuCl(S)-BINPO]SbF6 and [CyRuCl(S)-TolBINPO]SbF6 (Cy = eta6
      cymene), were synthesized from (CyRuCl2)(2) and the appropriate non-C2-symmetric
      bisphosphine monoxide ligands (S)-BINPO and (S)-TolBINPO (BINPO = 2,2'
      bis(diphenylphosphino)-1,1'-binaphthyl) in the presence of NaSbF6. When these
      complexes were mixed with AgSbF6 the resulting Lewis acids catalyzed the Diels
      Alder cycloaddition of cyclopentadiene and methacrolein. The product (2S)
      methylbicyclo[2.2.1]hept-5-ene-2-carboxaldehyde was obtained with excellent
      diastereoselectivity (up to 99%) and enantioselectivity (up to 99%) in several
      cases. When the complexes containing the analogous C2-symmetric bisphosphine
      ligands (S)-BINAP and (S)-TolBINAP were employed as catalysts, the Diels-Alder
      cycloadducts were obtained with much lower enantioselectivity (19 to 50%) for the
      opposite antipode. Although some of the effect may arise from chelate ring size
      change, much of the enhanced stereoselectivity of (RRu)-[CyRuCl(S)-BINPO]SbF6 and
      [CyRuCl(S)-TolBINPO]SbF6 can be attributed to the electronic asymmetry at the
      stereogenic Ru center.

PMID- 11456921
TI  - Rational design of fluorescein-based fluorescence probes. Mechanism-based design
      of a maximum fluorescence probe for singlet oxygen.
AB  - Fluorescein is one of the best available fluorophores for biological
      applications, but the factors that control its fluorescence properties are not
      fully established. Thus, we initiated a study aimed at providing a strategy for
      rational design of functional fluorescence probes bearing fluorescein structure.
      We have synthesized various kinds of fluorescein derivatives and examined the
      relationship between their fluorescence properties and the highest occupied
      molecular orbital (HOMO) levels of their benzoic acid moieties obtained by
      semiempirical PM3 calculations. It was concluded that the fluorescence properties
      of fluorescein derivatives are controlled by a photoinduced electron transfer
      (PET) process from the benzoic acid moiety to the xanthene ring and that the
      threshold of fluorescence OFF/ON switching lies around -8.9 eV for the HOMO level
      of the benzoic acid moiety. This information provides the basis for a practical
      strategy for rational design of functional fluorescence probes to detect certain
      biomolecules. We used this approach to design and synthesize 9-[2-(3-carboxy-9,10
      dimethyl)anthryl]-6-hydroxy-3H-xanthen-3-one (DMAX) as a singlet oxygen probe and
      confirmed that it is the most sensitive probe currently known for (1)O(2). This
      novel fluorescence probe has a 9,10-dimethylanthracene moiety as an extremely
      fast chemical trap of (1)O(2). As was expected from PM3 calculations, DMAX
      scarcely fluoresces, while DMAX endoperoxide (DMAX-EP) is strongly fluorescent.
      Further, DMAX reacts with (1)O(2) more rapidly, and its sensitivity is 53-fold
      higher than that of 9-[2-(3-carboxy-9,10-diphenyl)anthryl]-6-hydroxy-3H-xanthen-3
      ones (DPAXs), which are a series of fluorescence probes for singlet oxygen that
      we recently developed. DMAX should be useful as a fluorescence probe for
      detecting (1)O(2) in a variety of biological systems.

PMID- 11456922
TI  - Synthesis and characterization of regiorandom and regioregular poly(3
      octylfuran).
AB  - Poly(3-octylfuran) has been synthesized with three regioregularities: P3OF-95,
      P3OF-75, and P3OF-50, where the number signifies the percentage HT content. The
      95% HT material is highly crystalline with a structure similar to that of HT
      poly(3-octylthiophene), P3OT. The lamellar spacing is 22.1 A and the pi-stacking
      distance is 3.81 A. UV-vis spectroscopy reveals that P3OF-95 is aggregated in
      CHCl(3) solution, and solid films of P3OF-95, but not P3OF-75 or -50, show
      Davydov and exciton band splitting due to the interactions of the pi-systems in
      the stacked morphology. An estimate of the Davydov splitting is 0.15 eV (1200 cm(
      1)). P3OF is reversibly oxidized at 0.32 V vs ferrocene/ferrocenium, but
      increasing the potential to 1.15 V leads to irreversible oxidation. Films of P3OF
      may be p-doped with iodine vapor. Doped P3OF-95 and -75 films have electrical
      conductivities of 10(-2) and 10(-7) S/cm, respectively. The UV-vis-NIR spectra of
      the iodine-doped films are interpreted in terms of molecular-like transitions
      involving the LUMO, HOMO, HOMO-1, and transitions across a Peierls distortion
      induced gap in the intermolecular conduction band that is formed by the overlap
      of the pi-systems of the stacked partially oxidized chains. The conduction band
      gap estimated for P3OF-95 is 0.34 eV, and that for P3OF-75 is 0.9 eV. The P3OF
      samples are thermally stable in N(2) atmosphere to between 275 degrees C (P3OF
      50) and 380 degrees C (P3OF-95), but suffer thermal oxidation above 150 degrees C
      or light-induced oxidation at room temperature.

PMID- 11456923
TI  - Molecular dynamics and thermodynamics of protein-RNA interactions: mutation of a
      conserved aromatic residue modifies stacking interactions and structural
      adaptation in the U1A-stem loop 2 RNA complex.
AB  - Molecular dynamics (MD) simulations and free energy component analysis have been
      performed to evaluate the molecular origins of the 5.5 kcal/mol destabilization
      of the complex formed between the N-terminal RNP domain of U1A and stem loop 2 of
      U1 snRNA upon mutation of a conserved aromatic residue, Phe56, to Ala. MD
      simulations, including counterions and water, have been carried out on the wild
      type and Phe56Ala peptide-stem loop 2 RNA complexes, the free wild type and
      Phe56Ala peptides, and the free stem loop 2 RNA. The MD structure of the Phe56Ala
      stem loop 2 complex is similar to that of the wild type complex except the
      stacking interaction between Phe56 and A6 of stem loop 2 is absent and loop 3 of
      the peptide is more dynamic. However, the MD simulations predict large changes in
      the structure and dynamics of helix C and increased dynamic range of loop 3 for
      the free Phe56Ala peptide compared to the wild type peptide. Since helix C and
      loop 3 are highly variable regions of RNP domains, this indicates that a
      significant contribution to the reduced affinity of the Phe56Ala peptide for RNA
      results from cooperation between highly conserved and highly variable regions of
      the RNP domain of U1A. Surprisingly, these structural effects, which are
      manifested as cooperative free energy changes, occur in the free peptide, rather
      than in the complex, and are revealed only by study of both the initial and final
      states of the complexation process. Free energy component analysis correctly
      accounts for the destabilization of the Phe56Ala-stem loop 2 complex, and
      indicates that approximately 80% of the destabilization is due to the loss of the
      stacking interaction and approximately 20% is due to differences in U1A
      adaptation.

PMID- 11456924
TI  - Structural characterization of complexes between iminodiacetate blocked on
      styrene-divinylbenzene matrix (Chelex 100 resin) and Fe(III), Cr(III), and Zn(II)
      in solid phase by energy-dispersive X-ray diffraction.
AB  - Local structure of Fe(III), Cr(III), and Zn(II) cations has been determined on
      the amorphous sample by means of the difference method used for liquid systems.
      We recorded energy-dispersive X-ray diffraction spectra of a chelating resin
      (Chelex 100), containing paired iminodiacetate ions coupled to a styrene
      divinylbenzene support, in several ionic forms. Coordination geometry of Fe(III),
      Cr(III), and Zn(II) metal cations with Chelex 100 resin ligand sites, and
      conformation of the ligand groups have been determined.

PMID- 11456925
TI  - Development of multianalyte sensor arrays composed of chemically derivatized
      polymeric microspheres localized in micromachined cavities.
AB  - The development of a chip-based sensor array composed of individually addressable
      polystyrene-poly(ethylene glycol) and agarose microspheres has been demonstrated.
      The microspheres are selectively arranged in micromachined cavities localized on
      silicon wafers. These cavities are created with an anisotropic etch and serve as
      miniaturized reaction vessels and analysis chambers. A single drop of fluid
      provides sufficient analysis media to complete approximately 100 assays in these
      microetch pits. The cavities possess pyramidal pit shapes with trans-wafer
      openings that allows for both fluid flow through the microreactors/analysis
      chambers and optical access to the chemically sensitive microspheres.
      Identification and quantitation of analytes occurs via colorimetric and
      fluorescence changes to receptor and indicator molecules that are covalently
      attached to termination sites on the polymeric microspheres. Spectral data are
      extracted from the array efficiently using a charge-coupled device allowing for
      the near-real-time digital analysis of complex fluids. The power and utility of
      this new microbead array detection methodology is demonstrated here for the
      analysis of complex fluids containing a variety of important classes of analytes
      including acids, bases, metal cations, metabolic cofactors, and antibody
      reagents.

PMID- 11456926
TI  - Catalytic effects of dioxygen on intramolecular electron transfer in radical ion
      pairs of zinc porphyrin-linked fullerenes.
AB  - Dioxygen accelerates back electron transfer (BET) processes between a fullerene
      radical anion (C60) and a radical cation of zinc porphyrin (ZnP) in
      photolytically generated ZnP.+-C60.- and ZnP.+-H2P-C60.- radical ion pairs. The
      rate constant of BET increases linearly with increasing oxygen concentration
      without, however, forming reactive oxygen species, such as singlet oxygen or
      superoxide anion. When ferrocene (Fc) is used as a terminal electron donor moiety
      instead of ZnP (i.e., Fc-ZnP-C60), no catalytic effects of dioxygen were,
      however, observed for the BET in Fc+-ZnP-C60.-, that is, from C60.- to the
      ferricenium ion. In the case of ZnP-containing C60 systems, the partial
      coordination of O2 to ZnP.+ facilitates an intermolecular electron transfer (ET)
      from C60.- to O2. This rate-determining ET step is followed by a rapid
      intramolecular ET from O2.- to ZnP.+ in the corresponding O2.--ZnP.+ complex and
      hereby regenerating O2. In summary, O2 acts as a novel catalyst in accelerating
      the BET of the C60.--ZnP.+ radical ion pairs.

PMID- 11456927
TI  - Studies of reductive elimination reactions to form carbon-oxygen bonds from
      Pt(IV) complexes.
AB  - The platinum(IV) complexes fac-L(2)PtMe(3)(OR) (L(2) =
      bis(diphenylphosphino)ethane, o-bis(diphenylphosphino)benzene, R = carboxyl,
      aryl; L = PMe(3), R = aryl) undergo reductive elimination reactions to form
      carbon-oxygen bonds and/or carbon-carbon bonds. The carbon-oxygen reductive
      elimination reaction produces either methyl esters or methyl aryl ethers
      (anisoles) and L(2)PtMe(2), while the carbon-carbon reductive elimination
      reaction affords ethane and L(2)PtMe(OR). Choice of reaction conditions allows
      the selection of either type of coupling over the other. A detailed mechanistic
      study of the reductive elimination reactions supports dissociation of the OR(-)
      ligand as the initial step for the C-O bond formation reaction. This is followed
      by a nucleophilic attack of OR(-) upon a methyl group bound to the Pt(IV) cation
      to produce the products MeOR and L(2)PtMe(2). C-C reductive elimination proceeds
      from L(2)PtMe(3)(OR) by initial L (L = PMe(3)) or OR(-) (L(2) = dppe, dppbz)
      dissociation, followed by C-C coupling from the resulting five-coordinate
      intermediate. Our studies demonstrate that both C-C and C-O reductive elimination
      reactions from Pt(IV) are more facile in polar solvents, in the presence of Lewis
      acids, and for OR(-) groups that contain electron withdrawing substituents.

PMID- 11456928
TI  - Reaction of SC+(1D,3D) with H2O, NH3, and CH4: a density functional study.
AB  - Density Functional Theory has been used to explore quantitative details of the
      potential energy hypersurface for the insertion reaction of scandium ion into the
      O-H, N-H, and C-H bond of water, ammonia, and methane molecules leading to H2
      elimination. Both singlet and triplet state channels have been considered. On the
      basis of the obtained results, it is possible to conclude that for the molecules
      considered the reaction is a spin-forbidden process. Indeed, it starts in the
      triplet ground state and ends in the singlet state, the change of the spin state
      probably occurring immediately after the formation of the electrostatic complex
      intermediate.

PMID- 11456929
TI  - Structure assignment in the solid state by the coupling of quantum chemical
      calculations with NMR experiments: a columnar hexabenzocoronene derivative.
AB  - We present a quantum chemical ab initio study which demonstrates a new combined
      experimental and theoretical approach, whereby a comparison of calculated and
      experimental (1)H NMR chemical shifts allows the elucidation of structural
      arrangements in solid-state molecular ensembles, taking advantage of the marked
      sensitivity of the (1)H chemical shift to intermolecular interactions. Recently,
      Brown et al. have shown that, under fast magic-angle spinning (MAS) at 35 kHz,
      the resolution in a (1)H NMR spectrum of the solid phase of an alkyl-substituted
      hexabenzocoronene (HBC) derivative is sufficient to observe the hitherto
      unexpected resolution of three distinct aromatic resonances ( J. Am. Chem. Soc.
      1999, 121, 6712). Exploiting the additional information about proton proximities
      provided by (1)H double-quantum (DQ) MAS NMR spectroscopy, it was shown that the
      results are qualitatively consistent with the aromatic cores packing in a manner
      similar to that in unsubstituted HBC. Using the HBC-C(12) molecule as an example,
      we show here that the new combined experimental and theoretical approach allows
      the observed (1)H chemical shifts to be related in a quantitative manner to the
      intermolecular structure. In the quantum chemical calculations, a series of model
      systems of stacked HBC oligomers are used. On account of the marked dependence of
      the (1)H chemical shift to ring currents arising from nearby aromatic rings, the
      calculated (1)H chemical shifts are found to be very sensitive to the stacking
      arrangement of the HBC molecules. Moreover, the ring current effect is found to
      be particularly long range, with a considerable influence of the second neighbor,
      at a distance of 700 pm, being observed.

PMID- 11456930
TI  - Modulating charge separation and charge recombination dynamics in porphyrin
      fullerene linked dyads and triads: Marcus-normal versus inverted region.
AB  - Photoinduced charge separation (CS) and charge recombination (CR) processes have
      been examined in various porphyrin-fullerene linked systems (i.e., dyads and
      triads) by means of time-resolved transient absorption spectroscopy and
      fluorescence lifetime measurements. The investigated compounds comprise a
      homologous series of rigidly linked, linear donor-acceptor arrays with different
      donor-acceptor separations and diversified donor strength: freebase porphyrin-C60
      dyad (H2P-C60), zincporphyrin-C60 dyad (ZnP-C60), ferrocene-zincporphyrin-C60
      triad (Fc-ZnP-C60), ferrocene-freebase porphyrin-C60 triad (Fc-H2P-C60), and
      zincporphyrin-freebase porphyrin-C60 triad (ZnP-H2P-C60). Most importantly, the
      lowest lying charge-separated state of all the investigated systems, namely, that
      of ferrocenium ion (Fc+) and the C60 radical anion (C60.-) pair in the Fc-ZnP-C60
      triad, has been generated with the highest quantum yields (close to unity) and
      reveals a lifetime as long as 16 micros. Determination of CS and CR rate
      constants, together with the one-electron redox potentials of the donor and
      acceptor moieties in different solvents, has allowed us to examine the driving
      force dependence (-DeltaG0ET) of the electron-transfer rate constants (kET).
      Hereby, the semilogarithmic plots (i.e., log kET versus -DeltaG0ET) lead to the
      evaluation of the reorganization energy (lambda) and the electronic coupling
      matrix element (V) in light of the Marcus theory of electron-transfer reactions:
      lambda = 0.66 eV and V = 3.9 cm(-1) for ZnP-C60 dyad and lambda = 1.09 eV and V =
      0.019 cm(-1) for Fc-ZnP-C60, Fc-H2P-C60, and ZnP-H2P-C60 triads. Interestingly,
      the Marcus plot in Fc-ZnP-C60, Fc-H2P-C60, and ZnP-H2P-C60 has provided clear
      evidence for intramolecular CR located in both the normal and inverted regions of
      the Marcus parabola. The coefficient for the distance dependence of V (damping
      factor: betaCR = 0.58 A(-1) is deduced which depends primarily on the nature of
      the bridging molecule.

PMID- 11456931
TI  - Dimesitylketone O-oxide: spectroscopic characterization, conformation, and
      reaction modes: OH formation and OH capture.
AB  - Dimesitylketone O-oxide 1b was synthesized by photolysis of dimesityldiazomethane
      dissolved in an oxygen saturated CCl3F solution at 140 K. Conformation and
      geometry of 1b were determined by comparing measured NMR chemical shifts with the
      corresponding chemical shifts calculated at the DFT-IGLO level of theory where it
      had to be considered that the molecule exists in two enantiomeric forms. Measured
      and calculated 1H chemical shifts agree within 0.1 ppm while the calculated 13C
      shift of the COO carbon (210.6 ppm) differs by only 0.4 ppm from the measured
      shift of 211.0 ppm. The two mesityl rings are perpendicular to each other and
      enclose angles of 40 and 57 degrees with the COO plane. The preferred
      rearrangement process of 1b is an H migration from one of the ortho-methyl groups
      to the terminal O atom of the COO unit. The calculated activation enthalpy of
      this process is 12.7 kcal/mol (B3LYP/cc-pVTZ). In contrast, the activation
      enthalpy for isomerization to dioxirane is 5 kcal/mol higher. In CCl3F, the
      activation barrier for the thermal decay was determined to be 13.8 +/- 0.2
      kcal/mol and in acetonitrile 13.1 +/- 0.4 kcal/mol. H migration initiates
      cleavage of the OO bond and the production of an OH and a benzyl radical.
      Recombination of the latter in the solvent cage leads to the formation of 2
      methylhydroxy-pentamethylbenzophenone, while escape of the OH radical from the
      solvent cage yields a ketone. These results confirm the possibility of OH
      production from carbonyl oxides in the solution phase.

PMID- 11456932
TI  - p-Phenylenecarbenonitrene and its halogen derivatives: how does resonance
      interaction between a nitrene and a carbene center affect the overall electronic
      configuration?
AB  - A series of para-conjugatively coupled phenylenecarbenonitrenes [(4
      nitrenophenyl)methylene (3a), (4-nitrenophenyl)fluoromethylene (3b), (4
      nitrenophenyl)chloromethylene (3c), and (4-nitrenophenyl)bromomethylene (3d)]
      were generated in argon matrix at low temperature (10 or 13 K) and characterized
      by IR and UV/vis spectroscopy. Density functional theory (B3LYP/6-31G(d)) and ab
      initio (MCSCF, CASPT2) methods were used to study the ground- and some low-lying
      excited states of 3a-d. The experimental and computational data suggest that 3a-d
      have singlet ground states (S0) and can be thought of as quinonoidal biradicals.
      In all cases, the lowest triplet (T1) and quintet (Q1) states lie about 2 kcal
      mol(-1) and 28-29 kcal mol(-1), respectively, higher in energy than S0. On the
      other hand the substituent is found to have a significant effect on the relative
      energy of the second excited triplet (T2) state. This state tends to become
      relatively more stable as the ability of the substituent to enforce a closed
      shell configuration at the carbene subunit increases. Interestingly, the energy
      difference between the T2 and S0 states in 3a-d is found to depend linearly on
      the S-T gap of the corresponding phenylcarbenes 7a-d. This relationship is
      helpful in predicting when a substituted p-phenylenecarbenonitrene may have a
      triplet ground state instead of a singlet one.

PMID- 11456933
TI  - EPR spectroscopy of MRI-related Gd(III) complexes: simultaneous analysis of
      multiple frequency and temperature spectra, including static and transient
      crystal field effects.
AB  - For the first time, a very general theoretical method is proposed to interpret
      the full electron paramagnetic resonance (EPR) spectra at multiple temperatures
      and frequencies in the important case of S-state metal ions complexed in liquid
      solution. This method is illustrated by a careful analysis of the measured
      spectra of two Gd3+ (S = 7/2) complexes. It is shown that the electronic
      relaxation mechanisms at the origin of the EPR line shape arise from the combined
      effects of the modulation of the static crystal field by the random Brownian
      rotation of the complex and of the transient zero-field splitting. A detailed
      study of the static crystal field mechanism shows that, contrarily to the usual
      global models involving only second-order terms, the fourth and sixth order terms
      can play a non-negligible role. The obtained parameters are well interpreted in
      the framework of the physics of the various underlying relaxation processes. A
      better understanding of these mechanisms is highly valuable since they partly
      control the efficiency of paramagnetic metal ions in contrast agents for medical
      magnetic resonance imaging (MRI).

PMID- 11456934
TI  - Transient resonance Raman and density functional theory investigation of the 2
      fluorenylnitrenium ion.
AB  - We report a transient resonance Raman spectrum for the 2-fluorenylnitrenium ion
      obtained after photolysis of 2-azidofluorene. The 10 experimental Raman band
      frequencies of the transient spectrum show very good agreement with the computed
      frequencies from BPW91/cc-PVDZ density functional theory calculations for the 2
      fluorenylnitrenium ion. Our results confirm the assignment of the approximately
      460 nm transient absorption band formed after photolysis of 2-azidofluorene in
      water/acetonitrile or water solution to the singlet ground electronic state 2
      fluorenylnitrenium ion. Our study indicates the 2-fluorenylnitrenium has a large
      degree of iminocyclohexadienyl cation character with significant delocalization
      of the charge over both phenyl rings of the fluorene moiety. We compare our
      results for the 2-fluoreneylnitrenium ion to those previously reported for
      several other arylnitrenium ions.

PMID- 11456935
TI  - UDFT and MCSCF descriptions of the photochemical Bergman cyclization of
      enediynes.
AB  - Several singlet and triplet potential energy surfaces (PES) for the Bergman
      cyclization of cis-1,5-hexadiyne-3-ene (1a) have been computed by UDFT, CI,
      CASCI, CASSCF, and CASMP2 methods. It is found that the first six excited states
      of 1a can be qualitatively described as linear combinations of the configurations
      of weakly interacting ethylene and acetylene units. Although the symmetry
      relaxation from C2nu to C2 makes cyclization of the 13B state Woodward-Hoffmann
      allowed, it also increases the probability of competing cis-trans isomerization.
      Hydrogen atom abstraction is another plausible pathway because the terminal
      alkyne carbons possess a large radical character. In view of the competing
      processes, we conclude that the Bergman cyclization along the 13B path is
      unlikely despite its exothermicity (Delta = -42 kcal/mol). Calculations on cyclic
      analogues of 1a lead to similar conclusions. A less exothermic, but more
      plausible pathway for photochemical cyclization lies on the 2(1)A PES (Delta = 
      18 kcal/mol). Compared to the 1(1)A(1) and 1(3)B states, the 2(1)A state has less
      in-plane electron repulsion which may facilitate cyclization. The resulting p
      benzyne intermediate has an unusual electronic structure combining singlet
      carbene and open-shell diradical features. Deactivation of the 2(1)A state of 1a
      is a competing pathway.

PMID- 11456936
TI  - 35 GHz ENDOR characterization of the "very rapid" signal of xanthine oxidase
      reacted with 2-hydroxy-6-methylpurine (13C8): evidence against direct Mo-C8
      interaction.
AB  - Xanthine oxidase is a molybdenum-containing enzyme that catalyzes the
      hydroxylation of xanthine and a wide variety of other aromatic heterocycles. In
      the course of the reaction with xanthine and substrates such as 2-hydroxy-6
      methylpurine (HMP), the enzyme gives rise to a Mo(V) EPR signal, denoted "very
      rapid", that arises from an authentic catalytic intermediate. The two alternative
      catalytic mechanisms proposed for this enzyme differ critically in whether the
      distance between Mo and C8 of the purine nucleus in this intermediate is short
      enough to admit a direct bonding interaction. To examine this distance, we have
      performed 13C ENDOR measurements of the "very rapid" EPR signal generated by
      xanthine oxidase during reaction with 13C8-HMP. The resulting (13)C8 hyperfine
      tensor, A = [10.2(1), 7.0(1), 6.5(1)] MHz, is discussed in the framework of a
      detailed consideration of factors involved in extracting metrical parameters from
      an anisotropic hyperfine interaction composed of contributions from multiple
      sources, in particular, the effect of the local contributions from spin density
      on (13)C8. The analysis presented here gives a Mo...C distance whose value is
      expected to be ca. 2.7-2.9 A in the "very rapid" intermediates formed with both
      xanthine and HMP, consistent with plausible bond lengths for a Mo-O-C8 fragment
      where C8 is a trigonal-planar aromatic carbon. The difference from earlier
      conclusions is explained. The data thus do not support the existence of a direct
      Mo-C bond in the signal-giving species. This conclusion supports a mechanism that
      does not involve such an interaction and which begins with base-assisted
      nucleophilic attack of the Mo(VI)-OH group on the C-8 of substrate, with
      concomitant hydride transfer to the Mo=S group to give Mo(IV)-SH; the EPR-active
      "very rapid" species then forms by one-electron oxidation and deprotonation to
      yield the EPR-detectable Mo(V)OS(OR) species. We further discuss the complexities
      and limitations of the semiempirical method used to arrive at these conclusions.

PMID- 11456937
TI  - Reaction of cis- and trans-2-Butene-1,4-dial with 2'-deoxycytidine to form stable
      oxadiazabicyclooctaimine adducts.

PMID- 11456938
TI  - UV resonance Raman detection of a ligand vibration on ferric nitrosyl heme
      proteins.

PMID- 11456939
TI  - The origin of 1,4-asymmetric induction in the additions of chiral alcohols to
      ketenes.

PMID- 11456940
TI  - Maximum communication between coupled oxidations of dimetal units.

PMID- 11456941
TI  - Phosphite dehydrogenase: an unusual phosphoryl transfer reaction.

PMID- 11456942
TI  - Mechanism of nitric oxide synthase. Evidence that direct hydrogen atom
      abstraction from the O-H bond of NG-hydroxyarginine is not relevant to the
      mechanism.

PMID- 11456943
TI  - Screening of homogeneous catalysts by fluorescence resonance energy transfer.
      Identification of catalysts for room-temperature Heck reactions.

PMID- 11456944
TI  - Theoretical determination of the Co-C bond energy dissociation in cobalamins.

PMID- 11456945
TI  - Flash photolytic generation and study of the enol of 2-hydroxy-2-cyano-N
      methylacetamide in aqueous solution, leading to an empirically-based estimate of
      the keto-enol equilibrium constant for the parent unsubstituted acetamide in that
      medium.

PMID- 11456946
TI  - Efficient diastereoselective syntheses of chiral macrocycles via zirconocene
      coupling. Synthetic control of size and geometry.

PMID- 11456947
TI  - Annulation of alkenyl-substituted heterocycles via rhodium-catalyzed
      intramolecular C-H activated coupling reactions.

PMID- 11456948
TI  - Highly active oligomeric (salen)co catalysts for asymmetric epoxide ring-opening
      reactions.

PMID- 11456949
TI  - Effect of an internal anthranilamide turn unit on the structure and
      conformational stability of helically biased intramolecularly hydrogen-bonded
      dendrons.

PMID- 11456951
TI  - DFT study of the [2+2] cycloreversion of uracil dimer anion radical: waters
      matter.

PMID- 11456950
TI  - Validation of protein structure from preparations of encapsulated proteins
      dissolved in low viscosity fluids.

PMID- 11456952
TI  - Catalytic asymmetric solid-phase cyclopropanation.

PMID- 11456953
TI  - The importance of acyl chain placement on phospholipid mixing in the
      physiologically relevant fluid phase.

PMID- 11456954
TI  - A self-assembled metallomacrocyclic ionophore with high affinity and selectivity
      for Li+ and Na+.

PMID- 11456955
TI  - Murrastifoline-F: first total synthesis, atropo-enantiomer resolution, and
      stereoanalysis of an axially chiral N,C-coupled biaryl alkaloid.
AB  - The first total synthesis of the Murraya alkaloid murrastifoline-F (3), an
      unsymmetric, N,C-bonded heterobiarylic biscarbazole, is described. Starting from
      the likewise naturally occurring-but here synthetically prepared-"monomer"
      murrayafoline-A (6), lead tetraacetate-mediated oxidative non-phenolic biaryl
      coupling gives 3 as the main regioisomer. The existence of this natural product
      as a pair of stable atropo-enantiomers was demonstrated analytically through LC
      CD investigations. Preparatively, the racemate resolution succeeded by O
      demethylation, derivatization with Mosher's reagent, and chromatographic
      separation of the resulting diastereomers. The absolute configurations of the
      atropisomers were assigned by CD spectroscopy in combination with quantum
      chemical CD calculations at the stage of the alkaloid 3 and by ROESY experiments
      of the diastereomeric Mosher derivatives. In the root extract of the curry leaf
      plant Murraya koenigii (Rutaceae), murrastifoline-F (3) was found to exist as a
      56:44 mixture in favor of the M-enantiomer, by LC-CD coupling.

PMID- 11456956
TI  - The mechanism of base-promoted HF elimination from 4-fluoro-4-(4'
      nitrophenyl)butan-2-one: a multiple isotope effect study including the leaving
      group (18)F/(19)F KIE.
AB  - Leaving-group fluorine as well as the primary and secondary deuterium kinetic
      isotope effects (KIEs) have been determined for the base-promoted elimination of
      hydrogen fluoride from 4-fluoro-4-(4'-nitrophenyl)butan-2-one in aqueous
      solution. The elimination was studied for formate, acetate, and imidazole as the
      catalyzing base. The fluorine KIEs were determined using the accelerator-produced
      short-lived radionuclide (18)F in combination with natural (19)F. The (19)F
      substrate was labeled with (14)C in a remote position to enable radioactivity
      measurement of both isotopic substrates. The elimination reaction exhibits large
      primary deuterium KIEs: 3.2, 3.7, and 7.5 for formate, acetate, and imidazole,
      respectively, thus excluding the E1 mechanism. The corresponding C(4)-secondary
      deuterium KIEs are 1.038, 1.050 and 1.014 and the leaving group fluorine KIEs are
      1.0037, 1.0047 and 1.0013, respectively. The size of the fluorine KIEs
      corresponds to 5-15% of the estimated maximum of 1.03 for complete C-F bond
      breakage. No H/D exchange is observed during the reaction. The size and trends of
      the KIEs for the different bases are consistent with an E1cB-like E2 or an
      E1cB(ip) mechanism.

PMID- 11456957
TI  - The first general method for palladium-catalyzed Negishi cross-coupling of aryl
      and vinyl chlorides: use of commercially available Pd(P(t-Bu)(3))(2) as a
      catalyst.
AB  - With a single protocol, commercially available Pd(P(t-Bu)(3))(2) can effect the
      Negishi cross-coupling of a wide range of aryl and vinyl chlorides with aryl- and
      alkylzinc reagents. The process tolerates nitro groups, and it efficiently
      generates sterically hindered biaryls. In addition, a high turnover number
      (>3000) can be achieved.

PMID- 11456958
TI  - Catalytic asymmetric epoxidation of enones using La-BINOL-triphenylarsine oxide
      complex: structural determination of the asymmetric catalyst.
AB  - The catalytic asymmetric epoxidation of enones using the La-BINOL-Ph(3)As=O
      complex generated from La(O-i-Pr)(3), BINOL, and Ph(3)As=O in a ratio of 1:1:1 is
      described herein. Using 1-5 mol % of the asymmetric catalyst, a variety of
      enones, including a dienone and a cis-enone, were found to be epoxidized in a
      reasonable reaction time, providing the corresponding epoxy ketones in up to 99%
      yield and with more than 99% ee. The possible structure of the actual asymmetric
      catalyst has been clarified by various methods, including X-ray crystal structure
      analysis. This is the first X-ray analysis of an alkali-metal free lanthanoid
      BINOL complex. Although La(binaphthoxide)(2)(Ph(3)As=O)(2) (7) was observed as
      the major complex in the complexes' solution, generated from La(O-i-Pr)(3),
      BINOL, and Ph(3)As=O in a ratio of 1:1:1, the possible active species turned out
      to be the La-BINOL-Ph(3)As=O complex in a ratio of 1:1:1. A probable reaction
      mechanism of the catalytic asymmetric epoxidation of enones is also proposed,
      suggesting that preferential formation of a heterochiral complex is the reason
      for asymmetric amplification. Moreover, the interesting role of La(O-i-Pr)(3) for
      accelerating the epoxidations while maintaining high ee's is discussed.

PMID- 11456959
TI  - Biosynthesis of the validamycins: identification of intermediates in the
      biosynthesis of validamycin A by Streptomyces hygroscopicus var. limoneus.
AB  - To study the biosynthesis of the pseudotrisaccharide antibiotic, validamycin A
      (1), a number of potential precursors of the antibiotic were synthesized in (2)H
      , (3)H-, or (13)C-labeled form and fed to cultures of Streptomyces hygroscopicus
      var. limoneus. The resulting validamycin A from each of these feeding experiments
      was isolated, purified and analyzed by liquid scintillation counting, (2)H- or
      (13)C NMR or selective ion monitoring mass spectrometry (SIM-MS) techniques. The
      results demonstrate that 2-epi-5-epi-valiolone (9) is specifically incorporated
      into 1 and labels both cyclitol moieties. This suggests that 9 is the initial
      cyclization product generated from an open-chain C(7) precursor, D-sedoheptulose
      7-phosphate (5), by a DHQ synthase-like cyclization mechanism. A more proximate
      precursor of 1 is valienone (11), which is also incorporated into both cyclitol
      moieties. The conversion of 9 into 11 involves first epimerization to 5-epi
      valiolone (10), which is efficiently incorporated into 1, followed by
      dehydration, although a low level of incorporation of 2-epi-valienone (15) is
      also observed. Reduction of 11 affords validone (12), which is also incorporated
      specifically into 1, but labels only the reduced cyclitol moiety. The mode of
      introduction of the nitrogen atom linking the two pseudosaccharide moieties is
      not clear yet. 7-Tritiated valiolamine (8), valienamine (2), and validamine (3)
      were all not incorporated into 1, although each of these amines has been isolated
      from the fermentation, with 3 being most prevalent. Demonstration of in vivo
      formation of [7-(3)H]validamine ([7-(3)H]-3) from [7-(3)H]-12 suggests that 3 may
      be a pathway intermediate and that the nonincorporation of [7-(3)H]-3 into 1 is
      due to a lack of cellular uptake. We thus propose that 3, formed by amination of
      12, and 11 condense to form a Schiff base, which is reduced to the
      pseudodisaccharide unit, validoxylamine A (13). Transfer of a D-glucose unit to
      the 4'-position of 13 then completes the biosynthesis of 1. Other possibilities
      for the mechanism of formation of the nitrogen bridge between the two
      pseudosaccharide units are also discussed.

PMID- 11456960
TI  - Aib-rich peptides containing lactam-bridged side chains as models of the 3(10)
      helix.
AB  - Aib-rich side chain lactam-bridged oligomers with n =1, 2, 3, were designed and
      synthesized as putative models of the 3(10)-helix. These peptides were
      conformationally characterized in aqueous solution containing SDS micelles by CD,
      NMR, and computer simulations. The lactam bridge between the side chains of L-Glu
      and L-Lys in (i) and (i+3) positions was introduced in order to enhance the
      conformational preference toward the right-handed 3(10)-helix. The NMR results
      clearly indicate that there is an increase of 3(10)-helix formation upon chain
      elongation. In the dimer and trimer (n = 2 and n = 3, respectively, in the
      structure reported above) the observed NOE connectivities are compatible with the
      3(10)-helical arrangement, confirmed by the temperature coefficients of the amide
      proton resonances which suggest the presence of a hydrogen-bonded structure. The
      phi and psi dihedral angles of the structures obtained by molecular dynamics
      calculations are also compatible with the 3(10)-helix. Identification of the
      hydrogen-bond pattern indicate that C=O(i)- - -HN(i+3) hydrogen bonds, typical of
      the 3(10)-helical conformation, are highly probable in all low-energy structures.
      The CD spectra of these Aib-rich lactam-bridged oligopeptides, obtained in the
      same solvent system used for NMR experiments, provide important insight into the
      spectroscopic characteristics of the 3(10)-helix.

PMID- 11456961
TI  - Rational design and assembly of M(2)M'(3)L(6) supramolecular clusters with C(3h)
      symmetry by exploiting incommensurate symmetry numbers.
AB  - A rational approach to heterometallic cluster formation is described that uses
      incommensurate symmetry requirements at two different metals to control the
      stoichiometry of the assembly. Critical to this strategy is the proper design and
      synthesis of hybrid ligands with coordination sites selective toward each metal.
      The phosphino-catechol ligand 4-(diphenylphosphino)benzene-1,2-diol (H(2)L)
      possesses both hard catecholate and soft phosphine donor sites and serves such a
      role, using soft (C(2)-symmetric) and hard (C(3)-symmetric) metal centers. The
      ML(3) catecholate complexes (M = Fe(III), Ga(III), Ti(IV), Sn(IV)) have been
      prepared and characterized as C(3)-symmetry precursors for the stepwise assembly
      (aufbau) of heterometallic clusters. While the single-crystal X-ray structure of
      the Cs(2)[TiL(3)] salt shows a C(1) mer-configuration in the solid -state, room
      temperature solution NMR data of this and related complexes are consistent with
      either exclusive formation of the C(3)-fac-isomer with all PPh(2) donor sites syn
      to each other or facile fac/mer isomerization. Coordination of these [ML(3)](2)(
      ) (M = Ti(IV), Sn(IV)) metallaligands via their soft P donor sites to C(2)
      symmetric PdBr(2) units gives exclusively pentametallic [M(2)Pd(3)Br(6)L(6)](4)(
      ) (M = Ti, Sn) clusters. These clusters have been fully characterized by spectral
      and X-ray structural data as C(3h) mesocates with Cs(+) or protonated 1,4
      diazabicyclo[2.2.2]octane (DABCO.H(+)) cations incorporated into deep molecular
      clefts. Exclusive formation of this type of supramolecular species is sensitive
      to the nature of the counterions. Alkali cations such as K(+), Rb(+), and Cs(+)
      give high-yield formation of the respective clusters while NEt(3)H(+) and
      NMe(4)(+) yield none of the desired products. Extension of the aufbau assembly to
      produce related [M(2)Pd(3)Cl(6)L(6)](4)(-), [M(2)Pd(3)I(6)L(6)](4)(-), and
      [M(2)Cr(3)(CO)(12)L(6)](4)(-) (M = Ti, Sn) clusters has also been realized. In
      addition to this aufbau approach, self-assembly of several of these
      [M(2)Pd(3)Br(6)L(6)](4)(-) clusters from all eleven components (two M(IV), three
      PdBr(2), six H(2)L) was also accomplished under appropriate reaction conditions.

PMID- 11456962
TI  - Relationship of solution and protein-bound structures of DNA duplexes with the
      major intrastrand cross-link lesions formed on cisplatin binding to DNA.
AB  - DNA bases in the three-base-pair (3bp) region of duplexes with the two major
      lesions of cisplatin (cis-PtCl(2)(NH(3))(2)) with DNA, namely d(XGG) and d(XAG) (
      = N7-platinated base), differ in their relative positions by as much as
      approximately 3.5 A in structures in the literature. Such large differences
      impede drug design and assessments of the effects of protein binding on DNA
      structure. One recent and several past structures based on NMR-restrained
      molecular dynamics (RMD) differ significantly from the reported X-ray structure
      of an HMG-bound XGG 16-mer DNA duplex (Ohndorf, U.-M.; Rould, M. A.; He, Q.;
      Pabo, C. O.; Lippard, S. J. Nature 1999, 399, 708). This 16-mer structure has
      several significant novel and unique features (e.g., a bp step with large
      positive shift and slide). Hypothesizing that novel structural features in the
      XGG or XAG region of duplexes elude discovery by NMR methods (especially because
      of the flexible nature of the 3bp region), we studied an oligomer with only G.C
      bp's in the XGGY site by NMR methods for the first time. This 9-mer gave a 5'-G
      N1H signal with a normal shift and intensity and showed clear NOE cross-peaks to
      C NHb and NHe. We assigned for the first time (13)C NMR signals of a duplex with
      a GG lesion. These data, by adding NMR-based criteria to those inherent in NOESY
      and COSY data, have more specifically defined the structural features that should
      be present in an acceptable model. In particular, our data indicated that the
      sugar of the X residue has an N pucker and that the GG cross-link should have a
      structure similar to the original X-ray structure of cis-Pt(NH(3))(2)(d(pGpG))
      (Sherman S. E.; Gibson, D.; Wang, A. H.-J.; Lippard, S. J. J. Am. Chem. Soc.
      1988, 110, 7368). With these restrictions added to NOE restraints, an acceptable
      model was obtained only when we started our modeling with the 16-mer structural
      features. The new X-ray/NMR-based model accounted for the NOESY data better than
      NOE-based models, was very similar in structure to the 16-mer, and differed from
      solely NOE-based models. We conclude that all XGG and XAG (X = C or T) duplexes
      undoubtedly have structures similar to those of the 16-mer and our model. Thus,
      protein binding does not change greatly the structure of the 3bp region. The
      structure of this region can now be used in understanding structure-activity
      relationships needed in the design of new carrier ligands for improving Pt
      anticancer drug activity.

PMID- 11456963
TI  - Mossbauer characterization of the iron-sulfur clusters in Desulfovibrio vulgaris
      hydrogenase.
AB  - The periplasmic hydrogenase of Desulfovibrio vulgaris (Hildenbourough) is an all
      Fe-containing hydrogenase. It contains two ferredoxin type [4Fe-4S] clusters,
      termed the F clusters, and a catalytic H cluster. Recent X-ray crystallographic
      studies on two Fe hydrogenases revealed that the H cluster is composed of two sub
      clusters, a [4Fe-4S] cluster ([4Fe-4S](H)) and a binuclear Fe cluster ([2Fe](H)),
      bridged by a cysteine sulfur. The aerobically purified D. vulgaris hydrogenase is
      stable in air. It is inactive and requires reductive activation. Upon reduction,
      the enzyme becomes sensitive to O(2), indicating that the reductive activation
      process is irreversible. Previous EPR investigations showed that upon reoxidation
      (under argon) the H cluster exhibits a rhombic EPR signal that is not seen in the
      as-purified enzyme, suggesting a conformational change in association with the
      reductive activation. For the purpose of gaining more information on the
      electronic properties of this unique H cluster and to understand further the
      reductive activation process, variable-temperature and variable-field Mossbauer
      spectroscopy has been used to characterize the Fe-S clusters in D. vulgaris
      hydrogenase poised at different redox states generated during a reductive
      titration, and in the CO-reacted enzyme. The data were successfully decomposed
      into spectral components corresponding to the F and H clusters, and
      characteristic parameters describing the electronic and magnetic properties of
      the F and H clusters were obtained. Consistent with the X-ray crystallographic
      results, the spectra of the H cluster can be understood as originating from an
      exchange coupled [4Fe-4S]-[2Fe] system. In particular, detailed analysis of the
      data reveals that the reductive activation begins with reduction of the [4Fe
      4S](H) cluster from the 2+ to the 1+ state, followed by transfer of the reducing
      equivalent from the [4Fe-4S](H) subcluster to the binuclear [2Fe](H) subcluster.
      The results also reveal that binding of exogenous CO to the H cluster affects
      significantly the exchange coupling between the [4Fe-4S](H) and the [2Fe](H)
      subclusters. Implication of such a CO binding effect is discussed.

PMID- 11456964
TI  - Syntheses and structural and electrochemical characterizations of
      vanadatricarbadecaboranyl analogues of vanadocene and the structural
      characterization of the [Li(CH(3)CN)2+](6-CH(3)-nido-5,6,9-C(3)B(7)H(9-)
      tricarbadecaboranyl anion.
AB  - A single-crystal X-ray determination of the [Li(CH(3)CN)(2)(+)](6-CH(3)-nido
      5,6,9-C(3)B(7)H(9)(-)) salt has shown that the 6-CH(3)-nido-5,6,9-C(3)B(7)H(9)(-)
      tricarbadecaboranyl anion has a nido-cage geometry based on an octadecahedron
      missing the unique six-coordinate vertex. The resulting six-membered open face is
      puckered, with two of the cage carbons (C6 and C9) occupying the low-coordinate
      cage positions above the plane of the four remaining atoms (C5, B7, B8, and B10).
      The Li(+) ion is centered over the open face and is solvated by two acetonitrile
      molecules. The reactions of the 6-CH(3)-nido-5,6,9-C(3)B(7)H(9)(-) anion with
      various vanadium halide salts, including VCl(4), VCl(3), and VBr(2), each
      resulted in the isolation of the same five paramagnetic products (2-6) of
      composition V(CH(3)-C(3)B(7)H(9))(2). X-ray crystallographic determinations of 2
      5 showed that the complexes consist of two octadecahedral VC(3)B(7) fragments
      sharing a common vanadium vertex and established their structures as commo-V-(1-V
      4'-CH(3)-2',3',4'-C(3)B(7)H(9))(1-V-2-CH(3)-2,3,4-C(3)B(7)H(9)) (2), commo-V-(1-V
      5'-CH(3)-2',3',5'-C(3)B(7)H(9))(1-V-4-CH(3)-2,3,4-C(3)B(7)H(9)) (3), commo-V-(1-V
      5'-CH(3)-2',3',5'-C(3)B(7)H(9))(1-V-2-CH(3)-2,3,4-C(3)B(7)H(9)) (4), and commo-V
      (1-V-2-CH(3)-2,3,4-C(3)B(7)H(9))(2) (5). These complexes can be considered as
      tricarbadecaboranyl analogues of vanadocene, (eta(5)-C(5)H(5))(2)V. However,
      unlike vanadocene, these complexes are air- and moisture-stable and have only one
      unpaired electron. The five complexes differ with respect to one another in that
      they either (1) contain different enantiomeric forms of the CH(3)-C(3)B(7)H(9)
      cages, (2) have a different twist orientation of the two cages, or (3) have the
      methyl group of the CH(3)-C(3)B(7)H(9) cage located in either the 2 or 4 position
      of the cage. Subsequent attempts to oxidize the compounds with reagents such as
      Br(2) and Ag(+) were unsuccessful, illustrating the ability of the
      tricarbadecaboranyl anion to stabilize metals in low oxidation states. Consistent
      with this, both the electrochemical oxidation and the reduction of 2 were much
      more positive than those of the same oxidation state changes in vanadocene. The
      one-electron reduction of 2 is a remarkable 2.9 V positive of that of Cp(2)V.

PMID- 11456965
TI  - Catalytic growth and characterization of gallium nitride nanowires.
AB  - The preparation of high-purity and -quality gallium nitride nanowires is
      accomplished by a catalytic growth using gallium and ammonium. A series of
      catalysts and different reaction parameters were applied to systematically
      optimize and control the vapor-liquid-solid (VLS) growth of the nanowires. The
      resulting nanowires show predominantly wurtzite phase; they were up to several
      micrometers in length, typically with diameters of 10-50 nm. A minimum nanowire
      diameter of 6 nm has been achieved. Temperature dependence of photoluminescence
      spectra of the nanowires revealed that the emission mainly comes from wurtzite
      GaN with little contribution from the cubic phase. Moreover, the thermal
      quenching of photoluminescence was much reduced in the GaN nanowires. The Raman
      spectra showed five first-order phonon modes. The frequencies of these peaks were
      close to those of the bulk GaN, but the modes were significantly broadened, which
      is indicative of the phonon confinement effects associated with the nanoscale
      dimensions of the system. Additional Raman modes, not observed in the bulk GaN,
      were found in the nanowires. The field emission study showing notable emission
      current with low turn-on field suggests potential of the GaN nanowires in field
      emission applications. This work opens a wide route toward detailed studies of
      the fundamental properties and potential applications of semiconductor nanowires.

PMID- 11456966
TI  - A theoretical study of the alkylation reaction of toluene with methanol catalyzed
      by acidic mordenite.
AB  - A theoretical study of the alkylation reaction of toluene with methanol catalyzed
      by the acidic Mordenite (Si/Al = 23) is reported. Cluster DFT as well as
      periodical structure DFT calculations have been performed. Full reaction energy
      diagrams of the elementary reaction steps that lead to the formation of the three
      xylene isomers are given. The use of periodical structure calculations allows one
      to account for zeolite framework electrostatic contributions and steric
      constraints that take place in zeolitic catalysts. Especially the steric
      constraint energy contribution has a significant effect on the energies and bond
      formation paths. The activation energy barrier of p-xylene formation is found to
      be approximately 20 kJ/mol lower than the corresponding values for the formation
      of its isomers. Computed host-guest binding energies according to the DFT method
      need a correction due to the absence of the dispersive interaction with the
      zeolite wall. Apparent activation energies obtained with this correction are in
      good agreement with experimental data.

PMID- 11456967
TI  - ATOP dyes. optimization of a multifunctional merocyanine chromophore for high
      refractive index modulation in photorefractive materials.
AB  - This paper reports synthesis, characterization and structural optimization of
      amino-thienyl-dioxocyano-pyridine (ATOP) chromophores toward a multifunctional
      amorphous material with unprecedented photorefractive performance. The structural
      (dynamic NMR, XRD) and electronic (UV/vis, electrooptical absorption, Kerr effect
      measurements) characterization of the ATOP chromophore revealed a cyanine-type pi
      conjugated system with an intense and narrow absorption band (epsilon(max) = 140
      000 L mol(-)(1) cm(-)(1)), high polarizability anisotropy (deltaalpha(0) = 55 x
      10(-)(40) C V(-)(1) m(2)), and a large dipole moment (13 D). This combination of
      molecular electronic properties is a prerequisite for strong electrooptical
      response in photorefractive materials with low glass-transition temperature
      (T(g)). Other important materials-related properties such as compatibility with
      the photoconducting poly(N-vinylcarbazole) (PVK) host matrix, low melting point,
      low T(g), and film-forming capabilities were optimized by variation of four
      different alkyl substituents attached to the ATOP core. A morphologically stable
      PVK-based composite containing 40 wt % of ATOP-3 showed an excellent
      photorefractive response characterized by a refractive index modulation of Deltan
      approximately 0.007 and a gain coefficient of Gamma approximately 180 cm(-)(1) at
      a moderate electrical field strength of E = 35 V microm(-)(1). Even larger
      effects were observed with thin amorphous films consisting of the pure glass
      forming dye ATOP-4 (T(g) = 16 degrees C) and 1 wt % of the photosensitizer 2,4,7
      trinitro-9-fluorenylidene-malononitrile (TNFM). This material showed complete
      internal diffraction at a field strength of only E = 10 V microm(-)(1) and Deltan
      reached 0.01 at only E = 22 V microm(-)(1) without addition of any specific
      photoconductor.

PMID- 11456968
TI  - Electron delocalization and magnetic state of doubly-reduced polyoxometalates.
AB  - Different mechanisms of spin pairing in doubly reduced polyoxometalates are
      studied on the basis of quantum-chemical DFT calculations. Using the nitrosyl
      derivative of decamolybdate [Mo(10)O(25)(OMe)(6)(NO)](-) (I) as an example, we
      elucidate an important role of the delocalization of "blue electrons". The charge
      distributions and spin states are studied for the series of isomers of I
      differing by positions of methyl groups (modeled by hydrogens). Three different
      states are calculated for each isomer: spin triplet, spin-restricted singlet, and
      a broken symmetry state. If the quasihomogeneous distribution of the "blue
      electrons" density is weakly perturbed by protonation, the delocalization
      mechanism is responsible for the spin pairing. It is evidenced by the singlet
      ground state given by a spin-restricted solution. If the perturbation of charge
      distribution is strong enough and the "blue electrons" density is localized at
      several metal centers, the exchange mechanism becomes active. A lowest energy
      broken symmetry state indicates the antiferromagnetic nature of the singlet
      ground state. The modulation of magnetic interactions in reduced polyoxoanions by
      external perturbations provides new possibilities for design of molecular
      magnetic materials.

PMID- 11456969
TI  - A model for enzyme-substrate interaction in alanine racemase.
AB  - We report on a theoretical model for the complex of the enzyme alanine racemase
      with its natural substrate (L-alanine) and cofactor (pyridoxal 5'-phosphate).
      Electrostatic potentials were calculated and ionization states were predicted for
      all of the ionizable groups in alanine racemase. Some rather unusual charge
      states were predicted for certain residues. Tyr265' has an unusually low
      predicted pK(a) of 7.9 and at pH 7.0 has a predicted average charge of -0.37,
      meaning that 37% of the Tyr265' residues in an ensemble of enzyme molecules are
      in the phenolate form. At pH 8-9, the majority of Tyr265' side groups will be in
      the phenolate form. This lends support to the experimental evidence that Tyr265'
      is the catalytic base involved in the conversion of L-alanine to D-alanine.
      Residues Lys39 and Lys129 have predicted average charges of +0.91 and +0.14,
      respectively, at pH 7.0. Lys39 is believed to be the catalytic base for the
      conversion of D-alanine to L-alanine, and the present results show that, at least
      some of the time, it is in the unprotonated amine form and thus able to act as a
      base. Cys311', which is located very close to the active site, has an unusually
      low predicted pK(a) of 5.8 and at pH 7.0 has a predicted average charge of -0.72.
      The very low predicted charge for Lys129 is consistent with experimental evidence
      that it is carbamylated, since an unprotonated amine group is available to act as
      a Lewis base and form the carbamate with CO(2). Repeating the pK(a) calculations
      on the enzyme with Lys129 in carbamylated form predicts trends similar to those
      of the uncarbamylated enzyme. It appears that the enzyme has the ability to
      stabilize negative charge in the region of the active site. Implications for
      selective inhibitor design are discussed.

PMID- 11456970
TI  - First computational evidence for a catalytic bridging hydroxide ion in a
      phosphodiesterase active site.
AB  - Phosphodiesterases are clinical targets for a variety of biological disorders,
      because this superfamily of enzymes regulates the intracellular concentration of
      cyclic nucleotides that serve as the second messengers playing a critical role in
      a variety of physiological processes. Understanding the structure and mechanism
      of a phosphodiesterase will provide a solid basis for rational design of the more
      efficient therapeutics. Although a three-dimensional X-ray crystal structure of
      the catalytic domain of human phosphodiesterase 4B2B was recently reported, it is
      uncertain whether a critical bridging ligand in the active site is a water
      molecule or a hydroxide ion. The identity of this bridging ligand is
      theoretically determined by performing first-principles quantum chemical
      calculations on models of the active site. All the results obtained indicate that
      this critical bridging ligand in the active site of the reported X-ray crystal
      structure is a hydroxide ion, rather than a water molecule, expected to serve as
      the nucleophile to initialize the catalytic degradation of the intracellular
      second messengers.

PMID- 11456971
TI  - Geometry of simple molecules: nonbonded interactions, not bonding orbitals, and
      primarily determine observed geometries.
AB  - The forces responsible for the observed geometries of the YX(3) (Y = N or P; X =
      H, F, or Cl) molecules were studied through ab initio computations at the HF
      SCF/6-31G level. The calculated molecular orbitals were grouped as contributing
      primarily to (a) the covalent bonds, (b) the terminal atom nonbonding electrons
      (for X = F or Cl), and (c) the central atom nonbonding electrons. This grouping
      was accomplished through 3-D plotting and an atomic population analysis of the
      molecular orbitals. The molecules were then moved through a X-Y-X angular range
      from 90 degrees to 119 degrees, in four or five degree increments. Single-point
      calculations were done at each increment, so as to quantify the energy changes in
      the molecular orbital groups as a function of geometry. These calculations show
      that the nonbonding electrons are much more sensitive to geometry change than are
      the bonding orbitals, particularly in the trihalide compounds. The molecular
      orbitals representing the nonbonding electrons on the terminal atoms (both
      valence and core electrons) contribute to the spreading forces, as they favor a
      wider X-Y-X angle. The contracting forces, which favor a smaller X-Y-X angle,
      consist of the orbitals comprising the nonbonding electrons on the central atom
      (again, both valence and core electrons). The observed geometry is seen as the
      balance point between these two sets of forces. A simple interaction-distance
      model of spreading and contracting forces supports this hypothesis. Highly linear
      trends are obtained for both the nitrogen trihalides (R(2) = 0.981) and
      phosphorus trihalides (R(2) = 0.992) when the opposing forces are plotted against
      each other. These results suggest that a revision of the popular conceptual
      models (hybridization and VSEPR) of molecular geometry might be appropriate.

PMID- 11456972
TI  - Entropy control of the cross-reaction between carbon-centered and nitroxide
      radicals.
AB  - Absolute rate constants for the cross-coupling reaction of several carbon
      centered radicals with various nitroxides and their temperature dependence have
      been determined in liquids by kinetic absorption spectroscopy. The rate constants
      range from <2 x 10(5) M(-)(1) s(-)(1) to 2.3 x 10(9) M(-)(1) s(-)(1) and depend
      strongly on the structure of the nitroxide and the carbon-centered radical.
      Grossly, they decrease with increasing rate constant of the cleavage of the
      corresponding alkoxyamine. In many cases, the temperature dependence shows a non
      Arrhenius behavior. A model assuming a short-lived intermediate that is hindered
      to form the coupling product by an unfavorable activation entropy leads to a
      satisfactory analytic description. However, the behavior is more likely due to a
      barrierless single-step reaction with a low exothermicity where the free energy
      of activation is dominated by a large negative entropy term.

PMID- 11456973
TI  - Measurement of (13)C(alpha)-(13)C(beta) dipolar couplings in (15)N,(13)C,(2)H
      labeled proteins: application to domain orientation in maltose binding protein.
AB  - TROSY-based HN(CO)CA 2D and 3D pulse schemes are presented for measurement of
      (13)C(alpha)-(13)C(beta) dipolar couplings in high molecular weight
      (15)N,(13)C,(2)H-labeled proteins. In one approach, (13)C(alpha)-(13)C(beta)
      dipolar couplings are obtained directly from the time modulation of cross-peak
      intensities in a set of 2D (15)N-(1)HN correlated spectra recorded in both the
      presence and absence of aligning media. In a second approach 3D data sets are
      recorded with (13)C(alpha)-(13)C(beta) couplings encoded in a frequency
      dimension. The utility of the experiments is demonstrated with an application to
      an (15)N,(13)C,(2)H-labeled sample of the ligand free form of maltose binding
      protein. A comparison of experimental dipolar couplings with those predicted from
      the X-ray structure of the apo form of this two-domain protein establishes that
      the relative orientation of the domains in solution and in the crystal state are
      very similar. This is in contrast to the situation for maltose binding protein in
      complex with beta-cyclodextrin where the solution structure can be generated from
      the crystal state via a 11 degrees domain closure.

PMID- 11456974
TI  - Effect of fluorination: gas-phase structures of N,N-dimethylvinylamine and
      perfluoro-N,N-dimethylvinylamine.
AB  - The gas-phase structures of N,N-dimethylvinylamine, (CH(3))(2)NC(H)=CH(2) (1),
      and perfluoro-N,N-dimethylvinylamine, (CF(3))(2)NC(F)=CF(2) (2), were determined
      by gas electron diffraction and quantum chemical methods (B3LYP and MP2 with 6
      31G basis sets). The configuration around nitrogen is slightly pyramidal in both
      compounds, with the sum of the nitrogen bond angles 351.2(12) degrees and
      354.8(6) degrees in 1 and 2, respectively. In the parent compound 1, the
      (CH(3))(2)N group lies nearly in the plane of the vinyl group, and the nitrogen
      lone pair (lp) is almost perpendicular to this plane (Phi(C=C-N-lp) = 98(6)
      degrees). In the perfluorinated species 2, however, the (CF(3))(2)N group is
      oriented perpendicular to the vinyl plane, and the lone pair is parallel to the
      C=C bond (Phi(C=C-N-lp) = 2(5) degrees). A natural bond orbital analysis provides
      a qualitative explanation for this conformational change upon fluorination. The
      sterically unfavorable in-plane orientation of the dimethylamino group in 1 is
      stabilized by conjugation between the nitrogen lone pair and the C=C pi-bond. The
      anomeric effect between the lone pair and the C(alpha)-F sigma-bond in addition
      to steric effects favors the perpendicular orientation of the (CF(3))(2)N group
      in 2. Both quantum chemical methods reproduce the experimental structures
      satisfactorily.

PMID- 11456975
TI  - The elusive benzocyclobutenylidene: a combined computational and experimental
      attempt.
AB  - Ab initio and density functional theory calculations predict that
      benzocyclobutenylidene (1) has a singlet ground state in contrast to the parent
      phenylcarbene and many other simply substituted arylcarbenes. Calculations also
      predict that 1 should lie in a relatively deep potential well, while its triplet
      state is 14.5 kcal mol(-)(1) higher in energy. However, attempts to observe 1
      directly by photolysis of two different nitrogenous precursors were not
      successful. Irradiation of diazobenzocyclobutene (7) (lambda > 534 nm or lambda >
      300 nm) or azibenzocyclobutene (10) (lambda > 328 nm) in Ar matrixes at 10 K
      leads to the formation of the strained cycloalkyne 7-methylenecyclohepta-3,5-dien
      1-yne (3). (13)C-Labeled 3 was also prepared in a similar manner. There is very
      good agreement between experimental IR spectra and computationally derived
      harmonic vibrational frequencies for 3 and [(13)C]-3 and excellent agreement
      between observed and calculated isotopic shifts. Prolonged short-wavelength
      irradiation converts 3 into benzocyclobutadiene (5). Phenylacetylene (6) and
      benzocyclobutadiene dimer (11) were identified as products arising from flash
      vacuum pyrolysis of diazirine 10 at 500 degrees C.

PMID- 11456976
TI  - Electron self-exchange in the solid-state: cocrystals of hydroquinone and
      bipyridyl triazole.
AB  - Solid-state voltammetry, spectroscopy, and microscopy studies have been used to
      probe the proton and electron conductivity within a self-assembled cocrystal,
      HQBpt. This crystallographically defined material contains 3,5-bis(pyridin-2-yl)
      1,2,4-triazole, HBpt, dimers that are pi-stacked and hydrogen bonded to 1,4
      hydroquinone, H(2)Q, in a herringbone arrangement. When deposited onto platinum
      microelectrodes, the cocrystal exhibits a well-defined voltammetric response
      corresponding to oxidation of H(2)Q to the quinone, Q, across a wide range of
      voltammetric time scales, electrolyte compositions, and pH values. Scanning
      electron microscopy reveals that redox cycling in aqueous perchlorate solutions
      in which the pH is systematically varied from 1 to 7 triggers
      electrocrystallization and the extensive formation of rodlike crystals. Fast scan
      rate voltammetry reveals that the homogeneous charge transport diffusion
      coefficient, D(app), is independent of the perchlorate concentration for 0.1 <
      [ClO(4)(-)] < 1.0 M (pH 6.6) at 3.14 +/- 0.11 x 10(-)(9) cm(2) s(-)(1). Moreover,
      D(app) is independent of the perchloric acid concentration for concentrations
      greater than approximately 2.0 M, maintaining a value of 4.81 +/- 0.07 x 10(-)(8)
      cm(2) s(-)(1). The observation that D(app) is independent of the supporting
      electrolyte suggests that the rate-determining step for homogeneous charge
      transport is not the availability of charge-compensating counterions or protons,
      but the dynamics of electron self-exchange between H(2)Q and Q. We have used the
      Dahms-Ruff formalism to determine electron self-exchange rate constants which are
      2.84 +/- 0.22 x 10(9) and 9.69 +/- 0.73 x 10(10) M(-)(1) s(-)(1) for pH values
      greater than approximately 2.0 and less than -0.3, respectively. Significantly,
      these values are more than 2 orders of magnitude larger that those found for
      benzoquinone self-exchange reactions in aqueous solution. These results indicate
      that hydrogen bonds play an important role in supporting rapid electron transfer.
      The increase in D(app) between pH 1.0 and -0.3 is associated with protonation of
      the HBpt moieties, which triggers a reversible change in the material's
      structure.

PMID- 11456977
TI  - Deprotonation of phosphonic acids with M2+ cations for the design of neutral
      isostructural organic-inorganic hybrids.

PMID- 11456979
TI  - Solid-phase catalysis: a biomimetic approach toward ligands on dendritic arms to
      explore recyclable hydroformylation reactions.

PMID- 11456978
TI  - Investigation of the total synthesis of N1999-A2: implication of stereochemistry.

PMID- 11456980
TI  - Alkali metal loaded zeolite LiA: evidence for highly symmetrical Rb(-) and K(-).

PMID- 11456982
TI  - Cross-coupling reaction of oxo-pi-allylnickel complex generated from 1,3-diene
      under an atmosphere of carbon dioxide.

PMID- 11456981
TI  - The pK(a)'s of 2'-hydroxyl group in nucleosides and nucleotides.

PMID- 11456983
TI  - An atom-economical three-carbon chain extension of alkynes to form E-enol
      silanes.

PMID- 11456984
TI  - Palladium-catalyzed thioesterification of alkynes with O-methyl S-phenyl
      thiocarbonate.

PMID- 11456985
TI  - Polymers recognizing biomolecules based on a combination of molecular imprinting
      and proximity scintillation: a new sensor concept.

PMID- 11456986
TI  - NO affinities of s-nitrosothiols: a direct experimental and computational
      investigation of RS-NO bond dissociation energies.

PMID- 11456987
TI  - Synthesis and characterization of polyether-ester dendrimers from glycerol and
      lactic acid.

PMID- 11456988
TI  - A new asymmetric Wacker-type cyclization and tandem cyclization promoted by
      Pd(II)-spiro bis(isoxazoline) catalyst.

PMID- 11456989
TI  - Development of a novel method to study the rate-determining step during protein
      regeneration: application to the oxidative folding of RNase A at low temperature
      reveals BPTI-like kinetic traps.

PMID- 11456990
TI  - Enantioselective Claisen rearrangements: development of a first generation
      asymmetric acyl-Claisen reaction.

PMID- 11456992
TI  - A (2)H-labeling scheme for active-site counts in metallocene-catalyzed alkene
      polymerization.

PMID- 11456991
TI  - Magnetically aligned phospholipid bilayers at the parallel and perpendicular
      orientations for X-band spin-label EPR studies.

PMID- 11456993
TI  - The yield of strand breaks resulting from direct-type effects in crystalline DNA
      X-irradiated at 4 K and room temperature.

PMID- 11456994
TI  - Catalytic asymmetric allylic alkylation in water with a recyclable amphiphilic
      resin-supported P,N-chelating palladium complex.

PMID- 11456995
TI  - Sensitivity enhancement in solid-state (13)C NMR of synthetic polymers and
      biopolymers by (1)H NMR detection with high-speed magic angle spinning.

PMID- 11456996
TI  - Imidotitanium complexes as hydroamination catalysts: substantially enhanced
      reactivity from an unexpected cyclopentadienide/amide ligand exchange.

PMID- 11456997
TI  - Direct observation of Bronsted acidic sites in dehydrated zeolite H-ZSM5 using
      DFS-enhanced (27)Al MQMAS NMR spectroscopy.

PMID- 11456998
TI  - Hyperpolarized xenon-mediated cross-polarization to material surfaces observed at
      room temperature and above.

PMID- 11456999
TI  - Concerted evolution of structure and function in a miniature protein.

PMID- 11457000
TI  - Steric control of oxygenation regiochemistry in soybean lipoxygenase-1.

PMID- 11457001
TI  - A cheap, catalytic, scalable, and environmentally benign method for alkene
      epoxidations.

PMID- 11457003
TI  - Synthesis and reactivity of polydisulfonimides.
AB  - The first synthesis of alkyl disulfonimide oligomers is presented. In the process
      of synthesizing these oligomers, previously unreported reactivity of the N
      substituted disulfonimide functional group was discovered. Under basic
      conditions, unexpected lengthening of the oligomers occurs through a
      "transdisulfonimidation" reaction, whereby new disulfonimides are synthesized
      from existing ones by reaction with sulfonamide anion. This process appears to
      proceed via formation of a sulfene intermediate. Support for the E1cB(Rev)
      mechanism includes isotope scrambling, substituent effects, and sulfene trapping.

PMID- 11457005
TI  - Peptoid oligomers with alpha-chiral, aromatic side chains: effects of chain
      length on secondary structure.
AB  - Oligomeric N-substituted glycines or "peptoids" with alpha-chiral, aromatic side
      chains can adopt stable helices in organic or aqueous solution, despite their
      lack of backbone chirality and their inability to form intrachain hydrogen bonds.
      Helical ordering appears to be stabilized by avoidance of steric clash as well as
      by electrostatic repulsion between backbone carbonyls and pi clouds of aromatic
      rings in the side chains. Interestingly, these peptoid helices exhibit intense
      circular dichroism (CD) spectra that closely resemble those of peptide alpha
      helices. Here, we have utilized CD to systematically study the effects of
      oligomer length, concentration, and temperature on the chiral secondary structure
      of organosoluble peptoid homooligomers ranging from 3 to 20 (R)-N-(1
      phenylethyl)glycine (Nrpe) monomers in length. We find that a striking evolution
      in CD spectral features occurs for Nrpe oligomers between 4 and 12 residues in
      length, which we attribute to a chain length-dependent population of alternate
      structured conformers having cis versus trans amide bonds. No significant changes
      are observed in CD spectra of oligomers between 13 and 20 monomers in length,
      suggesting a minimal chain length of about 13 residues for the formation of
      stable poly(Nrpe) helices. Moreover, no dependence of circular dichroism on
      concentration is observed for an Nrpe hexamer, providing evidence that these
      helices remain monomeric in solution. In light of these new data, we discuss
      chain length-related factors that stabilize organosoluble peptoid helices of this
      class, which are important for the design of helical, biomimetic peptoids sharing
      this structural motif.

PMID- 11457007
TI  - Sequence-dependent correction of random coil NMR chemical shifts.
AB  - Random coil chemical shifts are commonly used to detect secondary structure
      elements in proteins in chemical shift index calculations. While this technique
      is very reliable for folded proteins, application to unfolded proteins reveals
      significant deviations from measured random coil shifts for certain nuclei. While
      some of these deviations can be ascribed to residual structure in the unfolded
      protein, others are clearly caused by local sequence effects. In particular, the
      amide nitrogen, amide proton, and carbonyl carbon chemical shifts are highly
      sensitive to the local amino acid sequence. We present a detailed, quantitative
      analysis of the effect of the 20 naturally occurring amino acids on the random
      coil shifts of (15)N(H), (1)H(N), and (13)CO resonances of neighboring residues,
      utilizing complete resonance assignments for a set of five-residue peptides Ac-G
      G-X-G-G-NH(2). The work includes a validation of the concepts used to derive
      sequence-dependent correction factors for random coil chemical shifts, and a
      comprehensive tabulation of sequence-dependent correction factors that can be
      applied for amino acids up to two residues from a given position. This new set of
      correction factors will have important applications to folded proteins as well as
      to short, unstructured peptides and unfolded proteins.

PMID- 11457008
TI  - Supramolecular chirogenesis in zinc porphyrins: mechanism, role of guest
      structure, and application for the absolute configuration determination.
AB  - The achiral syn folded (face-to-face conformation) host molecule of the ethane
      bridged bis(zinc porphyrin) transforms into the corresponding chiral extended
      anti bis-ligated species in the presence of enantiopure amine guests. The
      mechanism of the supramolecular chirogenesis is based upon the screw formation in
      bis(zinc porphyrin), arising from steric interactions between the largest
      substituent at the ligand's asymmetric carbon and peripheral alkyl groups of the
      neighboring porphyrin ring pointing toward the covalent bridge. The screw
      direction is determined by the guest's (amines) absolute configuration resulting
      in a positive chirality induced by (S)-enantiomers due to formation of the right
      handed screw, and a negative chirality produced by the left-handed screw of (R)
      enantiomers. The screw magnitude is strongly dependent upon the structure of the
      chiral guests. The amines with bulkier substituents result in stronger CD signals
      and larger (1)H NMR resonance splittings of enantiotopic protons. This system
      possesses a high degree of chiroptical activity, which allows the differentiation
      of one of the smallest homologous elements of organic chemistry, that is, the
      methyl and ethyl groups attached to the asymmetric carbon, and additionally,
      which senses a remote chiral center at a position beta to the amine binding
      group.

PMID- 11457010
TI  - Correlations of structure and electronic properties from EPR spectroscopy of
      hydroxylamine oxidoreductase.
AB  - Hydroxylamine oxidoreductase (HAO) from the autotrophic nitrifying bacterium
      Nitrosomonas europaea catalyzes the oxidation of NH(2)OH to HNO(2). The enzyme
      contains eight hemes per subunit which participate in catalytic function and
      electron transport. The structure of the enzyme shows a unique spatial
      arrangement of the eight hemes, subsets of which are now observed in four other
      proteins. The spatial arrangement displays three types of diheme pairing motifs.
      At least four of the eight hemes are electronically coupled in two
      distinguishable pairs and one of these pairs is at the active site of the enzyme.
      Here, the use of quantitative simulation of the EPR signals allows determination
      of exchange couplings, and assignments of signals and reduction potentials to
      hemes of the crystal structure. The absence of any obvious heme-to-heme bonding
      pathway in the crystal structure suggests that the observed exchange interactions
      are derived from direct electronic overlap of porphyrin orbitals. This provides
      evidence for heme pairs which function as biological two-electron redox centers
      in electron-transfer processes.

PMID- 11457011
TI  - Proton migration and tautomerism in protonated triglycine.
AB  - Proton migration in protonated glycylglycylglycine (GGG) has been investigated by
      using density functional theory at the B3LYP/6-31++G(d,p) level of theory. On the
      protonated GGG energy hypersurface 19 critical points have been characterized, 11
      as minima and 8 as first-order saddle points. Transition state structures for
      interconversion between eight of these minima are reported, starting from a
      structure in which there is protonation at the amino nitrogen of the N-terminal
      glycyl residue following the migration of the proton until there is fragmentation
      into protonated 2-aminomethyl-5-oxazolone (the b(2) ion) and glycine. Individual
      free energy barriers are small, ranging from 4.3 to 18.1 kcal mol(-)(1). The most
      favorable site of protonation on GGG is the carbonyl oxygen of the N-terminal
      residue. This isomer is stabilized by a hydrogen bond of the type O-H.N with the
      N-terminal nitrogen atom, resulting in a compact five-membered ring. Another
      oxygen-protonated isomer with hydrogen bonding of the type O-H.O, resulting in a
      seven-membered ring, is only 0.1 kcal mol(-)(1) higher in free energy.
      Protonation on the N-terminal nitrogen atom produces an isomer that is about 1
      kcal mol(-)(1) higher in free energy than isomers resulting from protonation on
      the carbonyl oxygen of the N-terminal residue. The calculated energy barrier to
      generate the b(2) ion from protonated GGG is 32.5 kcal mol(-)(1) via TS(6-->7).
      The calculated basicity and proton affinity of GGG from our results are 216.3 and
      223.8 kcal mol(-)(1), respectively. These values are 3-4 kcal mol(-)(1) lower
      than those from previous calculations and are in excellent agreement with
      recently revised experimental values.

PMID- 11457012
TI  - Raman spectroscopic and electrochemical characterization of myoglobin thin film:
      implication of the role of histidine 64 for fast heterogeneous electron transfer.
AB  - Myoglobin (Mb) thin films formed on various substrates have been characterized by
      using Raman spectroscopy, reflectance absorbance FT-IR, UV-vis absorption
      spectroscopy, and electrochemical methods. Raman spectra were obtained upon
      excitation within the Soret band as well as alpha-beta bands. The spin state
      marker bands observed from the Mb film in the 1550-1630 cm(-)(1) region
      (excitation at 514.5 nm) are approximately 20 cm(-)(1) higher than those of
      aqueous metMb having the high spin state. The 1210 cm(-)(1) band (methine bridge
      C-H vibration) also shifts to 1240 cm(-)(1) upon the formation of the film. These
      results indicate that the heme iron of myoglobin in the film is the ferric low
      spin state, and the iron atom is pulled to the heme plane. A comparison of the
      Raman spectra of the Mb film with that of an Mb-imidazole derivative leads to the
      conclusion that the distal histidine is responsible for the change in the
      spectral characteristics. The escape of water from the sixth position upon the
      formation of the Mb film may result in a conformational change at the heme distal
      pocket: the histidine residue at the E7 helical position (H64) moves toward the
      central iron and is coordinated with it through the N on the imidazole ring.
      These structural features facilitate the fast electron transfer between the thin
      protein film and the electrode. Distal histidine may serve as an electron
      transfer pathway as it does in cytochrome c.

PMID- 11457013
TI  - Simulated and NMR-derived backbone dynamics of a protein with significant
      flexibility: a comparison of spectral densities for the betaARK1 PH domain.
AB  - A 7.6 ns molecular dynamics trajectory of the betaARK1 PH domain in explicit
      water with appropriate ions was calculated at 300 K. Spectral densities at omega
      = 0, omega(N), and 0.87omega(H) and the model-free parameters were evaluated from
      the experimental as well as the simulated data, taking the anisotropic overall
      motion of the protein into account. Experimental and simulated spectral densities
      are in reasonable general agreement for NH bond vectors, where the corresponding
      motions have converged within the simulation time. A sufficient sampling of the
      motions for NH bonds within flexible parts of the protein requires a longer
      simulation time. The simulated spectral densities J(0) and J(omega(N)) are, on
      average, 4.5% and 16% lower than the experimental data; the corresponding numbers
      for the core residues are about 6%; the high-frequency spectral densities
      J(0.87omega(H)) are lower by, on average, 16% (21% for the core). The simulated
      order parameters, S(2), are also lower, although the overall disagreement between
      the simulation and experiment is less pronounced: 1% for all residues and 6% for
      the core. The observed systematic decrease of simulated spectral density and the
      order parameters compared to the experimental data can be partially attributed to
      the ultrafast librational motion of the NH bonds with respect to their peptide
      plane, which was analyzed in detail. This systematic difference is most
      pronounced for J(0.87omega(H)), which appears to be most sensitive to the slow,
      subnanosecond time scale of internal motion, whereas J(0) and J(omega(N)) are
      dominated by the overall rotational tumbling of the protein. Similar
      discrepancies are observed between the experimentally measured (15)N relaxation
      parameters (R(1), R(2), NOE) and their values calculated from the simulated
      spectral densities. The analysis of spectral densities provides additional
      information regarding the comparison of the simulated and experimental data, not
      available from the model-free analysis.

PMID- 11457014
TI  - Multi-state epoxidation of ethene by cytochrome P450: a quantum chemical study.
AB  - The epoxidation of ethene by a model for Compound I of cytochrome P450, studied
      by the use of density functional B3LYP calculations, involves two-state
      reactivity (TSR) with multiple electromer species, hence "multi-state
      epoxidation". The reaction is found to proceed in stepwise and effectively
      concerted manners. Several reactive states are involved; the reactant is an
      (oxo)iron(IV) porphyrin cation radical complex with two closely lying spin states
      (quartet and doublet), both of which react with ethene to form intermediate
      complexes with a covalent C-O bond and a carbon-centered radical (radical
      intermediates). The radical intermediates exist in two electromers that differ in
      the oxidation state of iron; Por(+)(*)Fe(III)OCH(2)CH(2)(*) and
      PorFe(IV)OCH(2)CH(2)(*) (Por = porphyrin). These radical intermediates exist in
      both the doublet- and quartet spin states. The quartet spin intermediates have
      substantial barriers for transformation to the quartet spin PorFe(III)-epoxide
      complex (2.3 kcal mol(-)(1) for PorFe(IV)OCH(2)CH(2)(*) and 7.2 kcal mol(-)(1)
      for Por(+)(*)Fe(III)OCH(2)CH(2)(*)). In contrast, the doublet spin radicals
      collapse to the corresponding PorFe(III)-epoxide complex with virtually no
      barriers. Consequently, the lifetimes of the radical intermediates are much
      longer on the quartet- than on the doublet spin surface. The loss of isomeric
      identity in the epoxide and rearrangements to other products arise therefore
      mostly, if not only, from the quartet process, while the doublet state
      epoxidation is effectively concerted (Scheme 7). Experimental trends are
      discussed in the light of the computed mechanistic scheme, and a comparison is
      made with closely related mechanistic schemes deduced from experiment.

PMID- 11457015
TI  - Sensitivity of tyrosyl radical g-values to changes in protein structure: a high
      field EPR study of mutants of ribonucleotide reductase.
AB  - The local electrostatic environment plays a critical role in determining the
      physicochemical properties of reactive radicals in proteins. High-field electron
      paramagnetic resonance (HF-EPR) spectroscopy has been used to determine the
      sensitivity of the tyrosyl radical g-values to local electrostatic environment.
      Site-specific mutants of ribonucleotide reductase from Escherichia coli were used
      to study the effect of introducing a charge group on the HF-EPR spectrum of the
      stable tyrosyl (Y122) radical. The changes affected by the mutations were small,
      but measurable. Mutation of isoleucine-74 to an arginine (I74R) or lysine (I74K)
      induced disorder in the hyperfine interactions. Similar effects were observed for
      the mutation of valine-136 to an arginine (V136R) or asparagine (V136N). For five
      or six mutants studied, the g(x)() component of the g-tensor was distributed. For
      the isoleucine-74 to lysine (I74K) and leucine-77 to phenylalanine (L77F)
      mutants, a shift of 1 x 10(-)(4) in g(x)() value was also detected. For the I74K
      mutant, it is shown that the shift is consistent with the introduction of a
      charged residue, but cannot be distinguished from changes in the electrostatic
      effect of the nearby diiron center. For the L77F mutant, the shift is induced by
      the diiron center. Using existing tyrosyl radical g-tensor measurements, we have
      developed a simple effective charge model that allows us to rationalize the
      effect of the local electrostatic environments in a number of proteins.

PMID- 11457016
TI  - A structural mode-coupling approach to 15N NMR relaxation in proteins.
AB  - The two-body Slowly Relaxing Local Structure (SRLS) model was applied to (15)N
      NMR spin relaxation in proteins and compared with the commonly used original and
      extended model-free (MF) approaches. In MF, the dynamic modes are assumed to be
      decoupled, local ordering at the N-H sites is represented by generalized order
      parameters, and internal motions are described by effective correlation times.
      SRLS accounts for dynamical coupling between the global diffusion of the protein
      and the internal motion of the N-H bond vector. The local ordering associated
      with the coupling potential and the internal N-H diffusion are tensors with
      orientations that may be tilted relative to the global diffusion and magnetic
      frames. SRLS generates spectral density functions that differ from the MF
      formulas. The MF spectral densities can be regarded as limiting cases of the SRLS
      spectral density. SRLS-based model-fitting and model-selection schemes similar to
      the currently used MF-based ones were devised, and a correspondence between
      analogous SRLS and model-free parameters was established. It was found that
      experimental NMR data are sensitive to the presence of mixed modes. Our results
      showed that MF can significantly overestimate order parameters and underestimate
      local motion correlation times in proteins. The extent of these digressions in
      the derived microdynamic parameters is estimated in the various parameter ranges,
      and correlated with the time scale separation between local and global motions.
      The SRLS-based analysis was tested extensively on (15)N relaxation data from
      several isotropically tumbling proteins. The results of SRLS-based fitting are
      illustrated with RNase H from E. coli, a protein extensively studied previously
      with MF.

PMID- 11457017
TI  - How curcumin works preferentially with water soluble antioxidants.
AB  - In this study we investigated physicochemical characteristics of the curcumin
      radical by pulse radiolysis and laser flash photolysis. Two methylated curcumin
      derivatives, methylcurcumin and trimethylcurcumin, were synthesized to explore
      the role of phenol hydroxy and beta-diketone moieties in the free radical
      chemistry of curcumin. Our results show that the initially generated beta-oxo
      alkyl transforms rapidly, probably via an intramolecular H-atom shift, into the
      phenoxyl-type curcumin radical. This phenoxyl does not react with oxygen, k <
      10(5) M(-1) s(-1), and can be repaired by any water-soluble antioxidant with
      appropriate redox potential, E(6) < 0.83 V, for example, with vitamin C, k = (6
      +/- 1) x 10(6) M(-1) s(-1). A molecular mechanism of cancer chemoprevention by
      curcumin is proposed, with special emphasis on the synergism with water-soluble
      antioxidants.

PMID- 11457018
TI  - Bridge-dependent electron transfer in porphyrin-based donor-bridge-acceptor
      systems.
AB  - Photoinduced electron transfer in donor-bridge-acceptor systems with zinc
      porphyrin (or its pyridine complex) as the donor and gold(III) porphyrin as the
      acceptor has been studied. The porphyrin moieties were covalently linked with
      geometrically similar bridging chromophores which vary only in electronic
      structure. Three of the bridges are fully conjugated pi-systems and in a fourth,
      the conjugation is broken. For systems with this bridge, the quenching rate of
      the singlet excited state of the donor was independent of solvent and
      corresponded to the rate of singlet energy transfer expected for a Forster
      mechanism. In contrast, systems with a pi-conjugated bridging chromophore show a
      solvent-dependent quenching rate that suggests electron transfer in the Marcus
      normal region. This is supported by picosecond transient absorption measurements,
      which showed formation of the zinc porphyrin radical cation only in systems with
      pi-conjugated bridging chromophores. On the basis of the Marcus and Rehm-Weller
      equations, an electronic coupling of 5-20 cm(-)(1) between the donor and acceptor
      is estimated for these systems. The largest coupling is found for the systems
      with the smallest energy gap between the donor and bridge singlet excited states.
      This is in good agreement with the coupling calculated with quantum mechanical
      methods, as is the prediction of an almost zero coupling in the systems with a
      nonconjugated bridging chromophore.

PMID- 11457020
TI  - Alkali metal cation-pi interactions observed by using a lariat ether model
      system.
AB  - The Na(+) or K(+) cation-pi interaction has been experimentally probed by using
      synthetic receptors that comprise diaza-18-crown-6 lariat ethers having ethylene
      sidearms attached to aromatic pi-donors. The side chains are 2-(3-indolyl)ethyl
      (7), 2-(3-(1-methyl)indolyl)ethyl (8), 2-(3-(5-methoxy)indolyl)ethyl (9), 2-(4
      hydroxyphenyl)ethyl (10), 2-phenylethyl (11), 2-pentafluorophenylethyl (12), and
      2-(1-naphthyl)ethyl (13). Solid-state structures are reported for six examples of
      alkali metal complexes in which the cation is pi-coordinated by phenyl, phenol,
      or indole. Indole-containing crown, 7, adopts a similar conformation when bound
      by NaI, KI, KSCN, or KPF(6). In each case, the macroring and both arenes
      coordinate the cation; the counteranion is excluded from the solvation sphere.
      NMR measurements in acetone-d(6) solution confirm the observed solid-state
      conformations of unbound 7 and 7.NaI. In 7.Na(+) and 7.K(+), the pyrrolo, rather
      than benzo, subunit of indole is the pi-donor for the alkali metal cation. Cation
      pi complexes were also observed for 10.KI and11.KI. In these cases, the
      orientation of the cation on the aromatic ring is in accord with the binding site
      predicted by computational studies. In contrast to the phenyl case (11) the
      pentafluorophenyl group of 12 failed to coordinate K(+). Solid-state structures
      are also reported for 7.NaPF(6), 10.NaI, 11.NaI, 13.KI, 13.KPF(6), and 9.NaI, in
      which cation-pi complexation is not observed. Steric and electrostatic
      considerations in the pi-complexation of alkali metal cations by these lariat
      ethers are thought to account for the observed complexation behavior or lack
      thereof.

PMID- 11457021
TI  - Insight into the complex and dynamic process of activation of matrix
      metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) are important hydrolytic enzymes with profound
      physiological and pathological functions in living organisms. MMPs are produced
      in their inactive zymogenic forms, which are subsequently proteolytically
      activated in an elaborate set of events. The propeptide in the zymogen blocks the
      active site, with a cysteine side-chain thiolate from this propeptide achieving
      coordination with the catalytically important zinc ion in the active site.
      Molecular dynamics simulations, ab initio calculations, and wet chemistry
      experiments presented herein argue for the critical importance of a protonation
      event at the coordinated thiolate as a prerequisite for the departure of the
      propeptide from the active site. Furthermore, a catalytically important glutamate
      is shown to coordinate transiently to the active-site zinc ion to "mask" the
      positive potential of the zinc ion and lower the energy barrier for dissociation
      of the protonated cysteine side chain from the zinc ion. In addition, a subtle
      conformational change by the propeptide is needed in the course of zymogen
      activation. These elaborate processes take place in concert in the activation
      process of MMPs, and the insight into these processes presented herein sheds
      light on a highly regulated physiological process with profound consequences for
      eukaryotic organisms.

PMID- 11457022
TI  - Signatures of beta-peptide unfolding in two-dimensional vibrational echo
      spectroscopy: a simulation study.
AB  - An ensemble of exciton Hamiltonians for the amide-I band of the folded and
      unfolded states of a helical beta-heptapeptide is generated using a molecular
      dynamics (MD) simulation. The correlated fluctuations of its parameters and their
      signatures in two-dimensional (2D) vibrational echo spectroscopy are computed.
      This technique uses infrared pulse sequences to provide ultrafast snapshots of
      molecular structural fluctuations, in analogy with multidimensional NMR. The
      present study demonstrates that, by combining a method of calculating the
      vibrational Hamiltonian from MD snapshots and the nonlinear exciton equations
      (NEE), it may be possible to simulate realistic multidimensional IR spectra of
      chemically and biologically interesting systems.

PMID- 11457024
TI  - Spin robustness of a new hybrid inorganic-organic high-spin molecule.

PMID- 11457025
TI  - Synthesis and properties of boranocarbonate: a convenient in situ CO source for
      the aqueous preparation of [(99m)Tc(OH(2))3(CO)3]+.

PMID- 11457030
TI  - Photolysis of thymine oxetanes produces triplet excited carbonyl compounds with
      high efficiency.

PMID- 11457032
TI  - Spin label enhanced NMR screening.

PMID- 11457033
TI  - Design and characterization of a heterodimeric coiled coil that forms exclusively
      with an antiparallel relative helix orientation.

PMID- 11457034
TI  - 1,6-anhydro-beta-l-hexopyranoses as potent synthons in the synthesis of the
      disaccharide units of bleomycin A(2) and heparin.

PMID- 11457035
TI  - Better substrates for bacterial transglycosylases.

PMID- 11457037
TI  - Sample concentration and separation for nanoliter-volume NMR spectroscopy using
      capillary isotachophoresis.

PMID- 11457038
TI  - The 2-deoxyribonolactone lesion produced in DNA by neocarzinostatin and other
      damaging agents forms cross-links with the base-excision repair enzyme
      endonuclease III.

PMID- 11457039
TI  - The importance of solute-solvent van der Waals interactions with interior atoms
      of biopolymers.

PMID- 11457042
TI  - Dinuclear Zn(2+) complexes of synthetic heptapeptides as artificial nucleases.

PMID- 11457043
TI  - Cisplatin-protein adducts are efficiently removed by glutathione but not by 5'
      guanosine monophosphate.

PMID- 11457044
TI  - Fluorescence anisotropy as a measure of chiral recognition.

PMID- 11457046
TI  - Differential plasmon spectroscopy as a tool for monitoring molecular binding to
      ultrathin gold films.

PMID- 11457047
TI  - Alignment of the HTLV-I Rex peptide bound to its target RNA aptamer from magnetic
      field-induced residual dipolar couplings and intermolecular hydrogen bonds.

PMID- 11457048
TI  - Properties of photogenerated tryptophan and tyrosyl radicals in structurally
      characterized proteins containing rhenium(I) tricarbonyl diimines.

PMID- 11457049
TI  - Selective oxidation at carbon adjacent to aromatic systems with IBX.

PMID- 11457052
TI  - Novel reactivity of ruthenium alkylidenes in protic solvents: degenerate
      alkylidene proton exchange.
AB  - A novel organometallic transformation is reported in which the alkylidene protons
      of water-soluble ruthenium alkylidenes 1 and 2 undergo nondestructive, degenerate
      exchange with solvent-derived deuterons in perdeuterated protic solvents such as
      D(2)O and CD(3)OD. Deuterated alkylidene complex (1-D) was isolated from a
      solution of alkylidene 1 in D(2)O, and the new alkylidene was fully characterized
      by (1)H, (2)H, (13)C, and (31)P NMR spectroscopy and fast-atom bombardment mass
      spectroscopy (FAB-MS). The rate of alkylidene proton exchange for this
      transformation was found to correlate with the bulk dielectric constant of the
      solvent or solvent mixtures employed. The data support a mechanism for proton
      exchange involving the dissociation of a chloride ion from the ruthenium metal
      center. The rate of alkylidene H/D exchange for alkylidene 2 was faster than the
      rate of exchange for alkylidene 1, demonstrating that relative rates of exchange
      are influenced by the electron densities at the metal centers of these complexes.
      Several additional ruthenium alkylidenes were found to undergo analogous
      alkylidene H/D exchange reactions, including parent alkylidene
      (Cy(3)P)(2)Cl(2)Ru=CHPh (3) in CD(2)Cl(2)/CD(3)OD mixtures. These data suggest
      that this novel reactivity may be general for an entire class of ruthenium
      alkylidenes provided that protic species are available in solution and that the
      dielectric constant of the reaction medium is sufficiently high to ionize the
      halide ligands.

PMID- 11457053
TI  - Stille couplings catalytic in tin: the "Sn-O" approach.
AB  - A one-pot tandem Pd-catalyzed hydrostannylation/Stille coupling protocol for the
      stereoselective generation of vinyltins and their subsequent union, employing
      only catalytic amounts of tin, is described. By recycling the organotin halide
      Stille byproduct back to organotin hydride, a hydrostannylation/cross-coupling
      sequence can be carried out with catalytic amounts of tin. Such a process is most
      effective with Me(3)SnCl serving as the tin source. This protocol allows a 94%
      reduction of the tin requirement, while maintaining good yields (up to 90%) for a
      variety of Stille products. Furthermore, since one cycle requires the tin to
      undergo at least four transformations, each moiety of trialkyltin is experiencing
      a minimum of 60 reactions over the course of the hydrostannylation/Stille
      sequence.

PMID- 11457054
TI  - Modulating artificial membrane morphology: pH-induced chromatic transition and
      nanostructural transformation of a bolaamphiphilic conjugated polymer from blue
      helical ribbons to red nanofibers.
AB  - Design and characterization of helical ribbon assemblies of a bolaamphiphilic
      conjugated polymer and their color-coded transformation into nanofibers are
      described. An L-glutamic acid modified bolaamphiphilic diacetylene lipid was
      synthesized and self-assembled into right-handed helical ribbons with micron
      scale length and nano scale thickness under mild conditions. The ribbon
      structures were further stabilized by polymerizing well-aligned diacetylene units
      to form bisfunctional polydiacetylenes (PDAs). Transitions from flat sheets to
      helical ribbons and tubes were observed by transmission electron microscopy. The
      helical ribbons appear to originate from the rupture of flat sheets along domain
      edges and the peeling off between stacked lipid layers. These results point to
      the applicability of chiral packing theory in bolaamphiphilic supramolecular
      assemblies. Contact mode atomic force microscopy observations revealed that high
      order existed in the surface packing arrangement. Hexagonal and pseudorectangular
      packings were observed in flat and twisted regions of the ribbons, respectively,
      suggesting a correlation between microscopic morphologies and nanoscopic packing
      arrangements. The tricarboxylate functionalities of the bolaamphiphilic lipid
      provide a handle for the manipulation of the bisfunctional PDAs' morphology.
      Increasing solution pH caused the fraying of helical ribbons into nanofibers
      accompanied by a sharp blue-to-red chromatic transition. A dramatic change in
      circular dichroism spectra was observed during this process, suggesting the loss
      of chirality in packing. A model is proposed to account for the pH-induced
      morphological change and chromatic transition. The color-coded transition between
      two distinct microstructures would be useful in the design of sensors and other
      "smart" nanomaterials requiring defined molecular templates.

PMID- 11457055
TI  - Enantioselective total synthesis of a potent antitumor antibiotic, fredericamycin
      A.
AB  - The asymmetric total synthesis of both enantiomers of the potent antitumor
      antibiotic fredericamycin A (1) is detailed based on the protocol for the
      construction of its peri-hydroxy polyaromatic skeleton bearing the chirality at
      the spiro carbon via a strong base-induced cycloaddition of suitably substituted
      homophthalic anhydrides (AB-ring unit) with an optically active CDEF-ring unit.
      Particular attention has been given to the novel synthesis of the optically
      active spiro carbon center by a stereospecific rearrangement of optically active
      benzofuzed-trans-epoxy acylates leading to spirocyclopentane-1,1'-indane systems.
      This method is quite useful for the construction of an optically active spiro
      compound and was applied to the synthesis of the optically pure CDEF-ring unit of
      1. Cycloaddition of the optically pure CDEF-ring unit to AB-ring units prepared
      via benzyne afforded two natural and unnatural-type hexacyclic compounds, which
      were converted to natural and unnatural enantiomers of synthetic 1, and the
      absolute configuration of natural 1 was determined as S.

PMID- 11457056
TI  - Carbon-carbon bond formation by electrophilic addition at the central carbon of
      the mu-eta(3)-allenyl/propargyl ligand on the Pd-Pd bond.
AB  - The mu-eta(3)-allenyl/propargyldipalladium complexes were synthesized by the
      reaction of the corresponding eta(1)-allenyl- or eta(1)-propargylpalladium
      complexes with Pd(2)(dba)(3). The X-ray diffraction analysis indicates that the
      dinuclear complex has a unique structure, in which two palladium, three carbon,
      two phosphorus, and one halogen atoms are in the same plane. These dinuclear
      complexes react with electrophiles, such as HCl or AcCl, at the central carbon of
      the mu-eta(3)-allenyl/propargyl ligand to give the mu-eta(3)
      vinylcarbenedipalladium complexes. Intramolecular reaction proceeded smoothly to
      give cyclization products quantitatively. Addition of a catalytic amount of a
      palladium(0) complex dramatically accelerated the carbon-carbon bond formation.
      The MO calculations on the mu-eta(3)-allenyl/propargyl complexes indicated that
      the reaction proceeds via orbital control.

PMID- 11457057
TI  - Polymerization of lactide with zinc and magnesium beta-diiminate complexes:
      stereocontrol and mechanism.
AB  - A series of zinc(II) and magnesium(II) alkoxides based upon a beta-diiminate
      ligand framework has been prepared. [(BDI-1)ZnO(i)Pr](2) [(BDI-1) = 2-((2,6
      diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene] exhibited
      the highest activity and stereoselectivity of the zinc complexes studied for the
      polymerization of rac- and meso-lactide to poly(lactic acid) (PLA). [(BDI
      1)ZnO(i)()Pr](2) polymerized (S,S)-lactide to isotactic PLA without epimerization
      of the monomer, rac-lactide to heterotactic PLA (P(r) = 0.94 at 0 degrees C), and
      meso-lactide to syndiotactic PLA (P(r) = 0.76 at 0 degrees C). The
      polymerizations are living, as evidenced by the narrow polydispersities of the
      isolated polymers in addition to the linear nature of number average molecular
      weight versus conversion plots and monomer-to-catalyst ratios. The substituents
      on the beta-diiminate ligand exert a significant influence upon the course of the
      polymerizations, affecting both the degree of stereoselectivity and the rate of
      polymerization. Kinetic studies with [(BDI-1)ZnO(i)Pr](2) indicate that the
      polymerizations are first order with respect to monomer (rac-lactide) and 1.56
      order in catalyst. Polymerization experiments with [(BDI-1)MgO(i)Pr](2) revealed
      that this complex is extremely fast for the polymerization of rac-lactide,
      polymerizing 500 equiv in 96% yield in less than 5 min at 20 degrees C.

PMID- 11457058
TI  - The first stereoselective total synthesis of quinine.
AB  - The first entirely stereoselective total synthesis of (-)-quinine is reported.

PMID- 11457059
TI  - Total synthesis of tropoloisoquinolines: imerubrine, isoimerubrine, and
      grandirubrine.
AB  - A unified, ready access to the tropoloisoquinoline alkaloids imerubrine (1),
      grandirubrine (2), and isoimerubrine (3) is delineated and features sequential
      application of the intramolecular Diels-Alder reaction of an acetylene-tethered
      oxazole and the [4 + 3] cycloaddition of an oxyallyl. A regioselective synthesis
      of 1 was achieved by stereo- and regioselective oxidation of an 8
      oxabicyclo[3.2.1]oct-6-en-3-one cycloadduct by means of the Moriarty method. Such
      a post-cycloaddition functionalization complements the synthetic utility of an
      alpha-alkoxy-substituted oxyallyl so as to broaden the scope of the oxyallyl [4 +
      3] cycloaddition reaction.

PMID- 11457060
TI  - A synthetic analogue of the active site of Fe-containing nitrile hydratase with
      carboxamido N and thiolato S as donors: synthesis, structure, and reactivities.
AB  - As part of our work on models of the iron(III) site of Fe-containing nitrile
      hydratase, a designed ligand PyPSH(4) with two carboxamide and two thiolate donor
      groups has been synthesized. Reaction of (Et(4)N)[FeCl(4)] with the deprotonated
      form of the ligand in DMF affords the mononuclear iron(III) complex
      (Et(4)N)[Fe(III)(PyPS)] (1) in high yield. The iron(III) center is in a trigonal
      bipyramidal geometry with two deprotonated carboxamido nitrogens, one pyridine
      nitrogen, and two thiolato sulfurs as donors. Complex 1 is stable in water and
      binds a variety of Lewis bases at the sixth site at low temperature to afford
      green solutions with a band around 700 nm. The iron(III) centers in these six
      coordinate species are low-spin and exhibit EPR spectra much like the enzyme. The
      pK(a) of the water molecule in [Fe(III)(PyPS)(H(2)O)](-) is 6.3 +/- 0.4. The
      iron(III) site in 1 with ligated carboxamido nitrogens and thiolato sulfurs does
      not show any affinity toward nitriles. It thus appears that at physiological pH,
      a metal-bound hydroxide promotes hydration of nitriles nested in close proximity
      of the iron center in the enzyme. Redox measurements demonstrate that the
      carboxamido nitrogens prefer Fe(III) to Fe(II) centers. This fact explains the
      absence of any redox behavior at the iron site in nitrile hydratase. Upon
      exposure to limited amount of dioxygen, 1 is converted to the bis-sulfinic
      species. The structure of the more stable O-bonded sulfinato complex
      (Et(4)N)[Fe(III)(PyP[SO(2)](2))] (2) has been determined. Six-coordinated low
      spin cyanide adducts of the S-bonded and the O-bonded sulfinato complexes,
      namely, Na(2)[Fe(III)(PyP[SO(2)](2))(CN)] (4) and
      (Et(4)N)(2)[Fe(III)(PyP[SO(2)](2))(CN)] (5), afford green solutions in water and
      other solvents. The iron(II) complex (Et(4)N)(2)[Fe(II)(PyPS)] (3) has also been
      isolated and structurally characterized.

PMID- 11457061
TI  - Alteration of the aurophilic interactions in trimeric gold(I) compounds through
      charge transfer. Behavior of solvoluminescent Au(3)(MeN=COMe)(3) in the presence
      of electron acceptors.
AB  - The ability of the triangular gold(I) complex, Au(3)(MeN=COMe)(3), which as a
      solid displays the novel property of solvoluminescence (see: Vickery, J. C.;
      Olmstead, M. M.; Fung, E. Y.; Balch, A. L. Angew.Chem., Int. Ed. Engl. 1997, 36,
      1179) to function as an electron donor has been demonstrated through
      spectroscopic studies and isolation of crystalline adducts with organic acceptor
      molecules. Four such adducts with nitro-9-fluorenones have been isolated and
      subject to single-crystal X-ray diffraction study. These are deep yellow
      [Au(3)(MeN=COMe)(3)].[2,4,7-trinitro-9-fluorenone], red
      [Au(3)(MeN=COMe)(3)].[2,4,5,7-tetranitro-9-fluorenone], red
      [Au(3)(MeN=COEt)(3)](2).[2,7-dinitro-9-fluorenone], and red
      [Au(3)(MeN=COEt)(3)](2).[2,4,7-trinitro-9-fluorenone]. The solid-state structures
      of [Au(3)(MeN=COMe)(3)].[2,4,7-trinitro-9-fluorenone] and
      [Au(3)(MeN=COMe)(3)].[2,4,5,7-tetranitro-9-fluorenone] consist of columns in
      which the planar gold(I) trimers and the nearly planar nitro-9-fluorenones are
      interleaved with the gold trimers making face-to-face contact with the
      nitroaromatic portion of the electron acceptor. Thus the organic acceptors
      disrupt the aurophilic interactions present in crystalline [Au(3)(MeN=COMe)(3)]
      itself. However, in [Au(3)(MeN=COEt)(3)](2).[2,7-dinitro-9-fluorenone] and
      [Au(3)(MeN=COEt)(3)](2).[2,4,7-trinitro-9-fluorenone], aurophilic interactions
      are found which produce dimers, [Au(3)(MeN=COEt)(3)](2), with nearly trigonal
      prismatic Au(6) cores. These dimers are interleaved with the nitro-9-fluorenone
      molecules to again form extended columns in which the components make face-to
      face contact. Despite the fact that the gold atoms in [Au(3)(MeN=COMe)(3)] and
      [Au(3)(MeN=COEt)(3)] are in exposed sites and only two-coordinate, there is no
      evidence of additional coordination of the nitro-9-fluorenones with gold centers
      in the crystalline adducts.

PMID- 11457062
TI  - Coordination sphere flexibility of active-site models for Fe-only hydrogenase:
      studies in intra- and intermolecular diatomic ligand exchange.
AB  - A series of dinuclear complexes, (mu-SRS)Fe(2)(CO)(6) (R = -CH(2)CH(2)-, 
      CH(2)CH(2)CH(2)-, -CH(2)-C(6)H(4)-CH(2)-; edt, pdt, and o-xyldt, respectively)
      has been examined for specific characteristics that might relate to structural
      similarity with the active site of Fe-only hydrogenases. Variable-temperature
      proton NMR studies display the fluxionality of the iron-dithiocyclohexane unit in
      (mu-pdt)Fe(2)(CO)(6) while in the (mu-o-xyldt)Fe(2)(CO)(6) compound, the bridge
      is fixed. Temperature-dependent (13)C NMR spectral studies establish
      intramolecular CO site exchange localized on discrete Fe(CO)(3) units in all
      complexes, which is influenced by steric effects of the mu-SRS unit. Kinetic
      studies of intermolecular CO/CN(-) ligand-exchange reactions establish
      associative or I(a) mechanisms in sequential steps to form the dicyano dianion,
      (mu-SRS)[Fe(CO)(2)(CN)](2)(=) with 100% selectivity. Theoretical calculations
      (DFT) of transition states in the intramolecular site-exchange processes lead to
      a rationale for the interesting cooperativity in the CN(-)/CO intermolecular
      ligand-exchange process. The hinge motion of the three light atom S-to-S bridge
      is related to a possible heterolytic H(2) activation/production process in the
      enzyme.

PMID- 11457063
TI  - Reactions of halofluorocarbons with group 6 complexes M(C(5)H(5))(2)L (M = Mo, W;
      L = C(2)H(4), CO). Fluoroalkylation at molybdenum and tungsten, and at
      cyclopentadienyl or ethylene ligands.
AB  - The molybdenum(II) and tungsten(II) complexes [MCp(2)L] (Cp = eta(5)
      cyclopentadienyl; L = C(2)H(4), CO) react with perfluoroalkyl iodides to give a
      variety of products. The Mo(II) complex [MoCp(2)(C(2)H(4))] reacts with perfluoro
      n-butyl iodide or perfluorobenzyl iodide with loss of ethylene to give the first
      examples of fluoroalkyl complexes of Mo(IV), MoCp(2)(CF(2)CF(2)CF(2)CF(3))I (8)
      and MoCp(2)(CF(2)C(6)F(5))I (9), one of which (8) has been crystallographically
      characterized. In contrast, the CO analogue [MoCp(2)(CO)] reacts with
      perfluorobenzyl iodide without loss of CO to give the crystallographically
      characterized salt, [MoCp(2)(CF(2)C(6)F(5))(CO)](+)I(-) (10), and the W(II)
      ethylene precursor [WCp(2)(C(2)H(4))] reacts with perfluorobenzyl iodide without
      loss of ethylene to afford the salt [WCp(2)(CF(2)C(6)F(5))(C(2)H(4))](+)I(-)
      (11). These observations demonstrate that the metal-carbon bond is formed first.
      In further contrast the tungsten precursor [WCp(2)(C(2)H(4))] reacts with
      perfluoro-n-butyl iodide, perfluoro-iso-propyl iodide, and pentafluorophenyl
      iodide to give fluoroalkyl- and fluorophenyl-substituted cyclopentadienyl
      complexes WCp(eta(5)-C(5)H(4)R(F))(H)I (12, R(F) = CF(2)CF(2)CF(2)CF(3); 15, R(F)
      = CF(CF(3))(2); 16, R(F) = C(6)F(5)); the Mo analogue MoCp(eta(5)
      C(5)H(4)R(F))(H)I (14, R(F) = CF(CF(3))(2)) is obtained in similar fashion. The
      tungsten(IV) hydrido compounds react with iodoform to afford the corresponding
      diiodides WCp(eta(5)-C(5)H(4)R(F))I(2) (13, R(F) = CF(2)CF(2)CF(2)CF(3); 18, R(F)
      = CF(CF(3))(2); 19, R(F) = C(6)F(5)), two of which (13 and 19) have been
      crystallographically characterized. The carbonyl precursors [MCp(2)(CO)] each
      react with perfluoro-iso-propyl iodide without loss of CO, to afford the exo
      fluoroalkylated cyclopentadiene M(II) complexes MCp(eta(4)-C(5)H(5)R(F))(CO)I
      (21, M = Mo; 22, M = W); the exo-stereochemistry for the fluoroalkyl group is
      confirmed by an X-ray structural study of 22. The ethylene analogues
      [MCp(2)(C(2)H(4))] react with perfluoro-tert-butyl iodide to yield the products
      MCp(2)[(CH(2)CH(2)C(CF(3))(3)]I (25, M = Mo; 26, M = W) resulting from
      fluoroalkylation at the ethylene ligand. Attempts to provide positive evidence
      for fluoroalkyl radicals as intermediates in reactions of primary and benzylic
      substrates were unsuccessful, but trapping experiments with CH(3)OD (to give
      R(F)D, not R(F)H) indicate that fluoroalkyl anions are the intermediates
      responsible for ring and ethylene fluoroalkylation in the reactions of secondary
      and tertiary fluoroalkyl substrates.

PMID- 11457064
TI  - On the regiospecificity of vanadium bromoperoxidase.
AB  - Vanadium haloperoxidase enzymes catalyze the oxidation of halide ions by hydrogen
      peroxide, producing an oxidized intermediate, which can halogenate an organic
      substrate or react with a second equivalent of hydrogen peroxide to produce
      dioxygen. Haloperoxidases are thought to be involved in the biogenesis of
      halogenated natural products isolated from marine organisms, including indoles
      and terpenes, of which many are selectively oxidized or halogenated. Little has
      been shown concerning the ability of the marine haloperoxidases to catalyze
      regioselective reactions. Here we report the regiospecific bromoperoxidative
      oxidation of 1,3-di-tert-butylindole by V-BrPO from the marine algae Ascophyllum
      nodosum and Corallina officinalis. Both enzymes catalyze the regiospecific
      oxidation of 1,3-di-tert-butylindole in a reaction requiring both H(2)O(2) and
      Br(-) as substrates, but which produce the unbrominated 1,3-di-tert-butyl-2
      indolinone product exclusively, in near quantitative yield (i.e. one H(2)O(2)
      consumed per product). By contrast, reactions with the controlled addition of
      aqueous bromine solution (HOBr = Br(2) = Br(3)(-)) produce three monobromo and
      one dibromo-2-indolinone products, all of which differ from the V-BrPO-catalyzed
      product. Further, reactivities of 1,3-di-tert-butyl-2-indolinone with both
      aqueous bromine and V-BrPO differ significantly and shed light onto the possible
      nature of the oxidizing intermediate. This is the first example of a
      regiospecific bromination by a vanadium haloperoxidase and further extends their
      usefulness as catalysts.

PMID- 11457065
TI  - Structural dynamics and cation interactions of DNA quadruplex molecules
      containing mixed guanine/cytosine quartets revealed by large-scale MD
      simulations.
AB  - Large-scale molecular dynamics (MD) simulations have been utilized to study G-DNA
      quadruplex molecules containing mixed GCGC and all-guanine GGGG quartet layers.
      Incorporation of mixed GCGC quartets into G-DNA stems substantially enhances
      their sequence variability. The mixed quadruplexes form rigid assemblies that
      require integral monovalent cations for their stabilization. The interaction of
      cations with the all-guanine quartets is the leading contribution for the
      stability of the four-stranded assemblies, while the mixed quartets are rather
      tolerated within the structure. The simulations predict that two cations are
      preferred to stabilize a four-layer quadruplex stem composed of two GCGC and two
      all-guanine quartets. The distribution of cations in the structure is influenced
      by the position of the GCGC quartets within the quadruplex, the presence and
      arrangement of thymidine loops connecting the guanine/cytosine stretches forming
      the stems, and the cation type present (Na(+) or K(+)). The simulations identify
      multiple nanosecond-scale stable arrangements of the thymidine loops present in
      the molecules investigated. In these thymidine loops, several structured pockets
      are identified capable of temporarily coordinating cations. However, no stable
      association of cations to a loop has been observed. The simulations reveal
      several paths through the thymidine loop regions that can be followed by the
      cations when exchanging between the central ion channel in the quadruplex stem
      and the surrounding solvent. We have carried out 20 independent simulations while
      the length of simulations reaches a total of 90 ns, rendering this study one of
      the most extensive MD investigations carried out on nucleic acids so far. The
      trajectories provide a largely converged characterization of the structural
      dynamics of these four-stranded G-DNA molecules.

PMID- 11457066
TI  - N6(2+) and N4(2+) dications and their n(12) and n(10) azido derivatives: DFT/GIAO
      MP2 theoretical studies.
AB  - The structures and energies of N(6)(2+) and N(4)(2+) were calculated by using the
      density functional theory method at the B3LYP/cc-aug-pVTZ level. The C(2)(h)()
      symmetric form 1 and D(infinity)(h) form 5 were found to be the stable minima for
      N(6)(2+) and N(4)(2+), respectively. Dissociation of 1 into 5 and N(2) was
      computed to be endothermic by 25.1 kcal/mol. (15)N NMR chemical shifts and
      vibrational frequencies of 1 and 5 were also calculated. Interactions of 1 and 5
      with azide ions were also probed representing N(12) and N(10).

PMID- 11457067
TI  - Structure and conformational behavior of biopolymers by density functional
      calculations employing periodic boundary conditions. I. The case of polyglycine,
      polyalanine, and poly-alpha-aminoisobutyric acid in vacuo.
AB  - Fully quantum mechanical calculations exploiting periodic boundary conditions
      (PBC) have been applied to the study of four different regular structures (alpha-
      and 3(10)-helix, fully extended and repeated gamma-turns) of the infinite
      polypeptides of glycine, alanine, and alpha-aminoisobutyric acid (Aib) in vacuo.
      alpha-Helix is predicted to be the most stable conformer for polyalanine and
      polyglycine, being stabilized over the 3(10)-helix mainly by more favorable
      dipole-dipole interactions. Contrary to previous suggestions, steric effects and
      hydrogen-bond strengths are comparable for both helix structures. 3(10)-Helix is
      preferred for poly-Aib, since in this case alpha-helix is strongly distorted due
      to unfavorable intrachain repulsions. Extended structures and repeated gamma
      turns are much less stable than helix structures for all of the polypeptides
      examined, mainly due to the absence of favorable long-range interactions. The
      optimized geometries are in good agreement with the available experimental data
      and reveal a remarkable dependence on the nature of the residue forming the
      polypeptides; at the same time the electronic and structural parameters of each
      residue strongly depend on the secondary structure of the polypeptides.

PMID- 11457068
TI  - Olefinic vs. aromatic pi-H interaction: a theoretical investigation of the nature
      of interaction of first-row hydrides with ethene and benzene.
AB  - The nature and origin of the pi-H interaction in both the ethene (olefinic) and
      benzene (aromatic) complexes of the first-row hydrides (BH(3), CH(4), NH(3),
      H(2)O, and HF) has been investigated by carrying out high level ab initio
      calculations. The results indicate that the strength of the pi-H interaction is
      enhanced as one progresses from CH(4) to HF. Unlike conventional H-bonds, this
      enhancement cannot be simply explained by the increase in electrostatic
      interactions or the electronegativity of the atom bound to the pi H-bonded
      proton. The contributions of each of the attractive (electrostatic, inductive,
      dispersive) and repulsive exchange components of the total binding energy are
      important. Thus, the inductive energy is highly correlated to the olefinic pi-H
      interaction as we progress from CH(3) to HF. On the other hand, both
      electrostatic and inductive energies are important in the description of the
      aromatic pi-H interaction. In either case, the contribution of dispersion
      energies is vital to obtain an accurate estimate of the binding energy. We also
      elaborate on the correlation of various interaction energy components with
      changes in geometries and vibrational frequencies. The red-shift of the nu(Y-H)
      mode is highly correlated to the inductive interaction. The dramatic increase in
      the exchange repulsion energies of these pi complexes as we progress from CH(4)
      to HF can be correlated to the blue-shift of the highly IR active out-of-plane
      bending mode of the pi system.

PMID- 11457069
TI  - Dissecting the photocycle of the bacteriorhodopsin E204Q mutant from kinetic
      multichannel difference spectra. Extension of the method of singular value
      decomposition with self-modeling to five components.
AB  - Kinetic multichannel difference spectroscopy in the visible spectral range of the
      Glu204 --> Gln(E204Q) site-directed mutant of bacteriorhodopsin revealed five
      spectrally distinct metastable intermediates, as for the wild type. Due to the
      perturbation of the extracellular proton release cluster, the late O intermediate
      accumulates in much higher amounts in this mutant, and the photocycle is not
      complicated by the pH-dependent branching observed in the wild type protein. This
      mutant is therefore more amenable than the wild type to the determination of the
      intermediate spectra with the method of singular value decomposition with self
      modeling, developed recently for three components (Zimanyi et al. Proc. Natl.
      Acad. Sci. U.S.A. 1999, 96, 4408-4413, 4414-4419). The method provides the most
      reliable spectra so far, defining the time evolution of the intermediates
      essential to the determination of the reaction scheme that describes the
      photocycle. The analysis confirms published results on this mutant by and large,
      but revises the locations of the L intermediates in the photocycle. In addition,
      it allows identification of the pH-dependent transitions of the photocycle, and
      offers an alternative mechanism for the pH dependence of the yield and kinetics
      of the late O intermediate.

PMID- 11457070
TI  - Solvent effects on heavy atom nuclear spin-spin coupling constants: a theoretical
      study of Hg-C and Pt-P couplings.
AB  - The computation of indirect nuclear spin-spin coupling constants, based on the
      relativistic two-component zeroth order regular approximate Hamiltonian, has been
      recently implemented by us into the Amsterdam Density Functional program.
      Applications of the code for the calculation of one-bond metal-ligand couplings
      of coordinatively unsaturated compounds containing (195)Pt and (199)Hg, including
      spin-orbit coupling or coordination effects by solvent molecules, show that
      relativistic density functional calculations are able to reproduce the
      experimental findings with good accuracy for the systems under investigation.
      Spin-orbit effects are rather small for these cases, while coordination of the
      heavy atoms by solvent molecules has a great impact on the calculated couplings.
      Experimental trends for different solvents are reproduced. An orbital-based
      analysis of the solvent effect is presented. The scalar relativistic increase of
      the coupling constants is of the same order of magnitude as the
      nonrelativistically obtained values, making a relativistic treatment essential
      for obtaining quantitatively correct results. Solvent effects can be of similar
      importance.

PMID- 11457071
TI  - A theoretical examination of the acid-catalyzed and noncatalyzed ring-opening
      reaction of an oxirane by nucleophilic addition of acetate. Implications to
      epoxide hydrolases.
AB  - Ab initio and density functional calculations have been performed to gain a
      better understanding of the epoxide ring-opening reaction catalyzed by epoxide
      hydrolase. The S(N)2 reaction of acetate with 1S,2S-trans-2-methylstyrene oxide
      to provide the corresponding diol acetate ester was studied with and without
      general-acid catalysis. MP2 and DFT (B3LYP) calculations predict, for the
      noncatalyzed reaction, a central barrier of approximately 20-21 kcal/mol
      separating the reactants from products depending on which carbon center in the
      epoxide is undergoing attack. From these gas-phase reactions the immediate
      alkoxide products are not energetically far below their associated transition
      states such that the reaction is predicted to be endothermic. Inclusion of
      aqueous solvation effects via a polarizable continuum model predicts the
      activation barrier to increase by almost 10 kcal/mol due to the solvation of the
      acetate ion nucleophile. The activation barrier for the epoxide ring-opening
      reaction is reduced to approximately 10 kcal/mol when phenol, as the general-acid
      catalyst, is included in the gas-phase calculations. This is due to the immediate
      product being the neutral ester rather than the corresponding alkoxide. The
      transition state in the general-acid-catalyzed reaction is earlier than that for
      the noncatalyzed reaction and the reaction is highly exothermic. Molecular
      mechanics calculations of 1S,2S-trans-2-methylstyrene oxide in the active site of
      murine epoxide hydrolase show two possible binding conformations. Both conformers
      have the epoxide oxygen forming hydrogen bonds with the acidic hydrogens of the
      catalytic tyrosines (Tyr381 and Tyr465). These two conformations likely lead to
      different products since the nucleophile (Asp333-CO(2)(-)) is positioned to react
      with either carbon center in the epoxide.

PMID- 11457072
TI  - Assessment of the existence of hyper-long axial Co(II)-N bonds in cobinamide
      B(12) models by using electron paramagnetic resonance spectroscopy.
AB  - Protein control of cobalt-axial nitrogen ligand bond length has been proposed to
      modulate the reactivity of vitamin B(12) coenzyme during the catalytic cycle of
      B(12)-dependent enzymes. In particular, hyper-long Co-N bonds may favor homolytic
      cleavage of the trans-cobalt-carbon bond in the coenzyme. X-ray crystallographic
      studies point to hyper-long bonds in two B(12) holoenzymes; however, mixed redox
      and ligand states in the crystals thwart clear conclusions. Since EPR theory
      predicts an increase in Co(II) hyperfine splitting as donation from the axial N
      donor ligand decreases, EPR spectroscopy could clarify the X-ray results.
      However, the theory is apparently undermined by the similar splitting reported
      for the 2-picoline (2-pic) and pyridine (py) adducts of Co(II) cobinamide
      (Co(II)Cbi(+)), adducts thought to have long and normal Co-N axial bond lengths,
      respectively. Cobinamides, with the B(12) 5,6-dimethylbenzimidazole loop removed,
      are excellent B(12) models. We studied Co(II)Cbi(+) adducts of unhindered 4
      substituted pyridines (4-X-py's) in ethylene glycol to separate orbital size
      effects from Co-N axial distance effects on these splittings. The linear increase
      in splitting with the decrease in 4-X-py basicity found is consistent with the
      theoretically predicted increase in unpaired electron spin density as axial N
      lone pair donation to Co(II) decreases. No adduct (and hence no hyper-long Co(II)
      N axial bond) was formed even by 8 M 2-pic, if the 2-pic was purified by a novel
      Co(III)-affinity distillation procedure designed to remove trace nitrogenous
      ligand impurities present in 2-pic distilled in the regular manner. Adducts
      formed by impurities in 2-pic and other hindered pyridines misled previous
      investigators into attributing results to adducts with long Co-N bonds. We find
      that many 2-substituted py's known to form adducts with simple synthetic Co
      models do not bind Co(II)Cbi(+). Thus, the equatorial corrin ring sterically
      impedes binding, making Co(II)Cbi(+) a highly selective binding agent for
      unhindered sp(2) N-donor ligands. Our results resolve the apparent conflict
      between EPR experiment and theory. The reported Co(II) hyperfine splitting of the
      enzyme-bound cofactor in five B(12) enzymes is similar to that of the relevant
      free cofactor. The most reasonable interpretation of this similarity is that the
      Co-N axial bond of the bound cofactor is not hyper-long in any of the five cases.

PMID- 11457073
TI  - Asymmetric Aldol reaction via a dinuclear zinc catalyst: alpha-hydroxyketones as
      donors.

PMID- 11457074
TI  - A new strategy for the stereoselective introduction of steroid side chain via
      alpha-alkoxy vinyl cuprates: total synthesis of a highly potent antitumor natural
      product OSW-1.

PMID- 11457075
TI  - Construction of persistent phenoxyl radical with intramolecular hydrogen bonding.

PMID- 11457076
TI  - Novel templating synthesis of necklace-shaped mono- and bimetallic nanowires in
      hybrid organic-inorganic mesoporous material.

PMID- 11457077
TI  - 2,2'-Bipyridine ligandoside: a novel building block for modifying DNA with intra
      duplex metal complexes.

PMID- 11457078
TI  - Magnetic excitations of CsMn(SO4)2.12d(2)O, measured by inelastic neutron
      scattering.

PMID- 11457079
TI  - Glycosyl sulfonylcarbamates: new glycosyl donors with tunable reactivity.

PMID- 11457080
TI  - Reaction of a coordinated cysteinato ligand with singlet oxygen: photooxidation
      of (cysteinato-N,S)bis(ethylenediamine)cobalt(III).

PMID- 11457081
TI  - Potentiometric sensors based on the inductive effect on the pK(a) of
      poly(aniline): a nonenzymatic glucose sensor.

PMID- 11457082
TI  - Cloning and heterologous expression of the macrotetrolide biosynthetic gene
      cluster revealed a novel polyketide synthase that lacks an acyl carrier protein.

PMID- 11457083
TI  - 5-Carbaphosphatranes: the first main group atrane bearing a 1-5 covalent bond.

PMID- 11457084
TI  - Clathrate III of group 14 exists after all.

PMID- 11457085
TI  - Studies on the biosynthesis of paraherquamide: concerning the mechanism of the
      oxidative cyclization of L-isoleucine to beta-methylproline.

PMID- 11457086
TI  - Ruthenium-catalyzed propargylic alkylation of propargylic alcohols with ketones:
      straightforward synthesis of gamma-keto acetylenes.

PMID- 11457087
TI  - Residual dipolar coupling TOCSY for direct through space correlations of base
      protons and phosphorus nuclei in RNA.

PMID- 11457088
TI  - Cation-pi interactions in sodiated phenylalanine complexes: is phenylalanine in
      the charge-solvated or zwitterionic form?

PMID- 11457089
TI  - myo-Inositol 1,4,5,6-tetrakisphosphate and myo-inositol 3,4,5,6
      tetrakisphosphate, two second messengers that may act as pH-dependent molecular
      switches.

PMID- 11457090
TI  - Lanthanum coordination networks based on unusual five-connected topologies.

PMID- 11457093
TI  - Product studies and laser flash photolysis on alkyl radicals containing two
      different beta-leaving groups are consonant with the formation of an olefin
      cation radical.
AB  - 1-Bromo-2-methoxy-1-phenylpropan-2-yl (3) and 2-methoxy-1-phenyl-1
      diphenylphosphatopropan-2-yl (4) were generated under continual photolysis from
      the respective PTOC precursors in a mixture of acetonitrile and methanol. The
      radicals undergo heterolytic fragmentation of the substituent in the beta
      position to generate the olefin cation radical (5). Z-2-Methoxy-1-phenylpropene
      (15) is the major product formed in the presence of 1,4-cyclohexadiene, and is
      believed to result from hydrogen atom transfer to the oxygen of the olefin cation
      radical, followed by deprotonation. Laser flash photolysis experiments indicate
      that reaction between 5 and 1,4-cyclohexadiene occurs with a rate constant of
      approximately 6 x 10(5) M(-1) s(-1). 2,2-Dimethoxy-1-phenylpropane (18) is
      observed as a minor product. Laser flash photolysis experiments place an upper
      limit on methanol trapping of 5 at k <1 x 10(3) M(-1) s(-1) and do not provide
      any evidence for the formation of reactive intermediates other than 5. The use of
      two PTOC precursors containing different leaving groups to generate a common
      olefin cation radical enables one to utilize product analysis to probe for the
      intermediacy of other reactive intermediates. The ratio of 15:18 is dependent
      upon hydrogen atom donor concentration, but is independent of the PTOC precursor.
      These observations are consistent with the proposal that both products result
      from trapping of 5 that is formed via heterolysis of 3 and 4.

PMID- 11457094
TI  - Enantioselective DNA threading dynamics by phenazine-linked.
AB  - The interactions between the stereoisomers of the chiral bis-intercalator [mu
      C4(cpdppz)(2)-(phen)(4)Ru(2)](4+) and DNA reveal interesting dynamic
      discrimination properties. The two enantiomers Delta-Delta and Lambda-Lambda both
      form very strong complexes with calf thymus DNA with similar thermodynamic
      affinities. By contrast, they display considerable variations in their binding
      kinetics. The Delta-Delta enantiomer has higher affinity for calf thymus DNA than
      for [poly(dA-dT)](2), and the association kinetics of the dimer to DNA, as well
      as to polynucleotides, requires a multiexponential fitting function. The
      dissociation reaction, on the other hand, could be described by a single
      exponential for [poly(dA-dT)](2), whereas two exponentials were required for
      mixed-sequence DNA. To understand the key mechanistic steps of the reaction, the
      kinetics was studied at varied salt concentration for different choices of DNA
      and chirality of the threading complex. The enantiomers were found to have
      markedly different dissociation rates, the Lambda-Lambda enantiomer dissociating
      about an order of magnitude faster than the Delta-Delta enantiomer. Also, the
      salt dependence of the dissociation rate constants differed between the
      enantiomers, being stronger for the Lambda-Lambda enantiomer than for the Delta
      Delta enantiomer. Since the dissociation reaction requires unthreading of bulky
      parts of the bis-intercalator through the DNA helix, a considerable
      conformational change of the DNA must be involved, possibly defining the rate
      limiting step.

PMID- 11457095
TI  - Photochemically removable silyl protecting groups.
AB  - Several o-phenol-containing alkoxyvinylsilanes were prepared and their
      photochemistry was investigated. These materials were prepared via
      hydrosilylation of the corresponding o-acetoxy arylacetylenes. Two major classes
      of photochemical processes were identified in these reactants: trans-->cis
      isomerization, leading to an intramolecular nucleophilic substitution process at
      silicon, and 1,5-silyl shift, leading to an unsymmetrical dialkoxysilane. The
      major outcome of this work is a novel class of photochemically removable
      protecting groups. Two alkyl substitutions on silicon, the dimethyl and
      diisopropyl, were examined. The latter is more stable and is preferred for
      protecting groups that must tolerate multiple steps or reagents. Protection of
      alcohols is generally performed starting with the arylethynyl acetate, which can
      be subjected to hydrosilylation, alcohol substitution, and acetate deprotection
      without isolation of intermediates. Two groups were studied in detail, the phenol
      and 2-naphthol vinyl silane derivatives. A variety of primary and secondary
      alcohols were protected with these reagents. These groups can be deprotected
      cleanly and in high yield by irradiation from 250 to 350 nm.

PMID- 11457096
TI  - Synthesis of poly(styrene sulfonate) brushes.
AB  - Dense poly(styrene sulfonate sodium salt) brushes were prepared on silicone
      wafers using a two-step procedure: polystyrene (PS) chains, terminated by a
      reactive trichlorosilane group, were first covalently grafted, and then the PS
      brush was converted to a poly(styrene sulfonate) brush by a soft sulfonation
      reaction. Ellipsometry and infrared spectroscopy in ATR were used to characterize
      the samples and to optimize the procedure: in particular, the sulfonation was
      shown to be homogeneous along the chain backbone and the neutralization complete.
      In some cases, the polymer layer revealed to be quite fragile: the chains were
      pulled out of the brush. A consolidation treatment which consisted in grafting
      oligomers inbetween the long PS chains significantly increased the robustness of
      the layer. This might be relevant for industrial applications.

PMID- 11457097
TI  - Hydrogen-bond-mediated photoinduced electron-transfer: novel dimethylaniline
      anthracene ensembles formed via Watson-Crick base-pairing.
AB  - The synthesis of a new, noncovalent anthracene-dimethylaniline dyad (ensemble I)
      held together via guanosine-cytidine Watson-Crick base-pairing interactions is
      reported. Upon excitation at 420 nm, photoinduced electron-transfer from the
      dimethylaniline donor to the singlet excited state of the anthracene acceptor
      occurs, as inferred from a combination of time-resolved fluorescence quenching
      and transient absorption measurements. In toluene at room temperature, the rate
      constants for photoinduced intraensemble electron-transfer and subsequent back
      electron-transfer (charge recombination) are k(CS) = (3.5 +/- 0.03) x 10(10) s(
      1) and k(CR) = (1.42 +/- 0.03) x 10(9) s(-1), respectively.

PMID- 11457098
TI  - How does the critical point change during a chemical reaction in supercritical
      fluids? A study of the hydroformylation of propene in supercritical CO(2).
AB  - An understanding of homogeneous catalysis in supercritical fluids requires a
      knowledge of the phase behavior and the variation in critical point as the
      reaction proceeds. In this paper, the critical temperatures, T(c) and pressures,
      P(c), have been measured for a considerable number of mixtures representing the
      various stages of the hydroformylation reaction of propene in supercritical CO(2)
      and different reactant concentrations. Critical point data have also been
      measured for all of the binary mixtures of the components (CO(2), H(2), CO,
      propene, n- and isobutyraldehyde) which are not available from the literature or
      can be deduced from published data. We use the stoichiometry of the reacting
      system to simplify greatly the phase behavior problem by defining a path through
      the otherwise multidimensional "phase space". Satisfactory modeling of the data
      (0.3% in T(c) and 3.0% in P(c)) has been achieved using the Peng-Robinson
      equation of state and ignoring all binary interactions which do not involve
      CO(2). The model is used to explore the strategies needed to avoid phase
      separation in continuous and batch reactions. At a given temperature, a batch
      reactor may need to be run under much higher pressures than a flow reactor if
      single-phase conditions are to be preserved throughout the course of the
      reaction. Most of the critical point data were measured acoustically, but a
      selection of points were validated using more traditional view-cell procedures.

PMID- 11457099
TI  - Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part I.
      Asymmetric addition of malonate nucleophiles.
AB  - Asymmetric alkylations of allylic geminal dicarboxylates with dialkyl malonates
      have been investigated. The requisite allylic geminal dicarboxylates are prepared
      in good yields and high isomeric purities by two catalytic methods, ferric
      chloride-catalyzed addition of acid anhydrides to alpha,beta-unsaturated
      aldehydes and palladium-catalyzed isomerization and addition reactions of
      propargylic acetates. The complex of palladium(0) and the chiral ligand derived
      from the diamide of trans-1,2-diaminocyclohexane and 2-diphenylphosphinobenzoic
      acid most efficiently catalyzed the asymmetric process to provide allylic
      carboxylate esters with high ee. By systematic optimization studies, factors
      affecting the enantioselectivity of the reaction have been probed. In general,
      higher ee's have been achieved with those conditions which facilitate kinetic
      capture of the incipient pi-allylpalladium intermediate. These conditions also
      proved effective for achieving high regioselectivities. The minor regioisomeric
      product was formed when reactive substrates or achiral ligands were employed for
      the reaction, and could be minimized through the use of the chiral ligand. Under
      the established conditions, the alkylation of various gem-dicarboxylates afforded
      monoalkylated products in high yields with greater than 90% ee. The process
      constitutes the equivalent of an addition of a stabilized nucleophile to a
      carbonyl group with high asymmetric induction.

PMID- 11457100
TI  - Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part II.
      Scope and applications.
AB  - An enantioselective synthesis of allylic esters has been achieved by a novel
      asymmetric alkylation of allylic gem-dicarboxylates. The catalyst derived from
      palladium(0) and R,R-1,2-di(2'-diphenylphosphinobenzamido)cyclohexene efficiently
      induced the alkylation process with a variety of nucleophiles to provide allylic
      esters as products in good yield. High regio- and enantioselectivities were
      observed in the alkylation with most nucleophiles derived from malonate, whereas
      a modest level of ee's was obtained in the reactions with less reactive
      nucleophiles such as bis(phenylsulfonyl)ethane. In the latter case, a slow
      addition procedure proved effective, leading to significantly improved ee's. The
      utility of the alkylation products was demonstrated by several synthetically
      useful transformations including allylic isomerizations, allylic alkylations, and
      Claisen rearrangements. Using these reactions, the chirality of the initial
      allylic carbon-oxygen bond could be transferred to new carbon-oxygen, carbon
      carbon, or carbon-nitrogen bonds in a predictable fashion with high
      stereochemical fidelity. The conversion of gem-diesters to chiral esters by the
      substitution reaction is the equivalent of an asymmetric carbonyl addition by
      stabilized nucleophiles. In conjunction with the subsequent reactions that occur
      with high stereospecificity, allylic gem-dicarboxylates serve as synthons for a
      double allylic transformation.

PMID- 11457101
TI  - Synthetic and theoretical studies on group-transfer imidoylation of
      organotellurium compounds. remarkable reactivity of isonitriles in comparison
      with carbon monoxide in radical-mediated reactions.
AB  - Imidoylation of organotellurium compounds with isonitriles has been investigated
      in conjunction with the radical-mediated C1 homologation reaction by using CO and
      isonitriles. Carbon-centered radicals generated photochemically or thermally from
      organotellurium compounds react with isonitriles in a group-transfer manner to
      give the corresponding imidoylated products. Organotellurium compounds have been
      found to serve as effective precursors of a wide variety of stabilized radicals,
      namely benzyl, alpha-alkoxy, alpha-amino, and acyl radicals, which take part in
      the imidoylation with high efficiency. The reactions are compatible with various
      functional groups, and can be carried out in various solvents including
      environmentally benign water. The reactivity of isonitriles has been compared
      with that of CO through competition experiments, and the results indicate that
      isonitriles are superior to CO as radical acceptors in reactions with stabilized
      radicals. The origin of the differences has been addressed in theoretical studies
      with density functional theory calculations using the B3LYP hybrid functional.
      The calculations suggest that both carbonylation and imidoylation proceed with
      low activation energies, and that there are virtually no differences in the
      kinetic sense. Instead, it indicates that thermodynamic effects, namely
      differences in the stability of the acyl and the imidoyl radicals, control the
      overall course of the reactions.

PMID- 11457102
TI  - Thermolysis of free-radical initiators: tert-butylazocumene and its 1,3- and 1,4
      bisazo and 1,3,5-trisazo analogues.
AB  - Four tert-butylazocumenes (4-7) were prepared from the corresponding
      cyanobenzenes, and their nitrogen evolution kinetics and products were analyzed.
      In combination with TEMPO, the simplest compound, tert-butylazocumene (4), shows
      promise as a "one-radical" initiator of styrene polymerization. The ABNO-trapped
      cumyl radical 29 is a particularly stable trialkylhydroxylamine, whose
      thermolysis half-life is 2.1 h at 150 degrees C. Taking advantage of this
      stability, we trapped the cumyl radical centers from 7 to afford tris adduct 32a.
      While the behavior of the meta bisazoalkane 6 can be mostly predicted from that
      of 4, the para isomer 5 exhibits both unusual products and kinetics, attributed
      to the formation of quinodimethane 33 via azo-containing radical 34. In fact,
      flash vacuum pyrolysis of 5 allowed observation of the (1)H and (13)C NMR spectra
      of 33, whose persistence even at ambient temperature showed that this
      quinodimethane is far more stable than the parent 36. Finally, evidence is
      presented that 7 is an initiator of star polymerization.

PMID- 11457103
TI  - Parallel synthesis of a vitamin D(3) library in the solid-phase.
AB  - A highly efficient synthesis of the vitamin D(3) system on solid support is
      described. Two synthetic strategies for the solid-phase synthesis of vitamin D(3)
      were developed. One is for 11-hydroxy analogues, and the other is for most other
      synthetic analogues. In the latter strategy, the sulfonate-linked CD-ring 58 was
      initially immobilized on PS-DES resin to give solid-supported CD-ring 63 (Scheme
      10). Similarly, solid-supported CD-ring 63 was prepared by attachment of the CD
      ring 10 to the chlorosulfonate resin 64. The vitamin D(3) system was synthesized
      by Horner-Wadsworth-Emmons reaction of the A-ring phosphine oxide to a solid
      supported CD-ring, followed by simultaneous introduction of the side chain and
      cleavage from resin with a Cu(I)-catalyzed Grignard reagent. Parallel synthesis
      of the vitamin D(3) analogues was accomplished by a split and pool methodology
      utilizing radio frequency encoded combinatorial chemistry, and a manual parallel
      synthesizer for side chain diversification and deprotection. Additionally, we
      demonstrated the synthesis of various A-rings in a similar protocol for efficient
      preparation of building blocks.

PMID- 11457104
TI  - Theoretical study of electron, proton, and proton-coupled electron transfer in
      iron bi-imidazoline complexes.
AB  - A comparative theoretical investigation of single electron transfer (ET), single
      proton transfer (PT), and proton-coupled electron transfer (PCET) reactions in
      iron bi-imidazoline complexes is presented. These calculations are motivated by
      experimental studies showing that the rates of ET and PCET are similar and are
      both slower than the rate of PT for these systems (Roth, J. P.; Lovel, S.; Mayer,
      J. M. J. Am. Chem. Soc. 2000, 122, 5486). The theoretical calculations are based
      on a multistate continuum theory, in which the solute is described by a
      multistate valence bond model, the transferring hydrogen nucleus is treated
      quantum mechanically, and the solvent is represented as a dielectric continuum.
      For electronically nonadiabatic electron transfer, the rate expressions for ET
      and PCET depend on the inner-sphere (solute) and outer-sphere (solvent)
      reorganization energies and on the electronic coupling, which is averaged over
      the reactant and product proton vibrational wave functions for PCET. The small
      overlap of the proton vibrational wave functions localized on opposite sides of
      the proton transfer interface decreases the coupling for PCET relative to ET. The
      theory accurately reproduces the experimentally measured rates and deuterium
      kinetic isotope effects for ET and PCET. The calculations indicate that the
      similarity of the rates for ET and PCET is due mainly to the compensation of the
      smaller outer-sphere solvent reorganization energy for PCET by the larger
      coupling for ET. The moderate kinetic isotope effect for PCET arises from the
      relatively short proton transfer distance. The PT reaction is found to be
      dominated by solute reorganization (with very small solvent reorganization
      energy) and to be electronically adiabatic, leading to a fundamentally different
      mechanism that accounts for the faster rate.

PMID- 11457105
TI  - Modeling the active sites in metalloenzymes. 3. Density functional calculations
      on models for [Fe]-hydrogenase: structures and vibrational frequencies of the
      observed redox forms and the reaction mechanism at the Diiron Active Center.
AB  - Optimized structures for the redox species of the diiron active site in [Fe]
      hydrogenase as observed by FTIR and for species in the catalytic cycle for the
      reversible H(2) oxidation have been determined by density-functional calculations
      on the active site model, [(L)(CO)(CN)Fe(mu-PDT)(mu-CO)Fe(CO)(CN)(L')](q)(L =
      H(2)O, CO, H(2), H(-); PDT = SCH(2)CH(2)CH(2)S, L' = CH(3)S(-), CH(3)SH; q = 0, 1
      , 2-, 3-). Analytical DFT frequencies on model complexes (mu-PDT)Fe(2)(CO)(6) and
      [(mu-PDT)Fe(2)(CO)(4)(CN)(2)](2)(-) are used to calibrate the calculated CN(-)
      and CO frequencies against the measured FTIR bands in these model compounds. By
      comparing the predicted CN(-) and CO frequencies from DFT frequency calculations
      on the active site model with the observed bands of D. vulgaris [Fe]-hydrogenase
      under various conditions, the oxidation states and structures for the diiron
      active site are proposed. The fully oxidized, EPR-silent form is an Fe(II)-Fe(II)
      species. Coordination of H(2)O to the empty site in the enzyme's diiron active
      center results in an oxidized inactive form (H(2)O)Fe(II)-Fe(II). The
      calculations show that reduction of this inactive form releases the H(2)O to
      provide an open coordination site for H(2). The partially oxidized active state,
      which has an S = (1)/(2) EPR signal, is an Fe(I)-Fe(II) species. Fe(I)-Fe(I)
      species with and without bridging CO account for the fully reduced, EPR-silent
      state. For this fully reduced state, the species without the bridging CO is
      slightly more stable than the structure with the bridging CO. The correlation
      coefficient between the predicted CN(-) and CO frequencies for the proposed model
      species and the measured CN(-) and CO frequencies in the enzyme is 0.964. The
      proposed species are also consistent with the EPR, ENDOR, and Mossbauer
      spectroscopies for the enzyme states. Our results preclude the presence of
      Fe(III)-Fe(II) or Fe(III)-Fe(III) states among those observed by FTIR. A proposed
      reaction mechanism (catalytic cycle) based on the DFT calculations shows that
      heterolytic cleavage of H(2) can occur from (eta(2)-H(2))Fe(II)-Fe(II) via a
      proton transfer to "spectator" ligands. Proton transfer to a CN(-) ligand is
      thermodynamically favored but kinetically unfavorable over proton transfer to the
      bridging S of the PDT. Proton migration from a metal hydride to a base (S, CN, or
      basic protein site) results in a two-electron reduction at the metals and
      explains in part the active site's dimetal requirement and ligand framework which
      supports low-oxidation-state metals. The calculations also suggest that species
      with a protonated Fe-Fe bond could be involved if the protein could accommodate
      such species.

PMID- 11457106
TI  - Highly luminescent silicon nanocrystals with discrete optical transitions.
AB  - A new synthetic method was developed to produce robust, highly crystalline,
      organic-monolayer passivated silicon (Si) nanocrystals in a supercritical fluid.
      By thermally degrading the Si precursor, diphenylsilane, in the presence of
      octanol at 500 degrees C and 345 bar, relatively size-monodisperse sterically
      stabilized Si nanocrystals ranging from 15 to 40 A in diameter could be obtained
      in significant quantities. Octanol binds to the Si nanocrystal surface through an
      alkoxide linkage and provides steric stabilization through the hydrocarbon chain.
      The absorbance and photoluminescence excitation (PLE) spectra of the nanocrystals
      exhibit a significant blue shift in optical properties from the bulk band gap
      energy of 1.2 eV due to quantum confinement effects. The stable Si clusters show
      efficient blue (15 A) or green (25-40 A) band-edge photoemission with
      luminescence quantum yields up to 23% at room temperature, and electronic
      structure characteristic of a predominantly indirect transition, despite the
      extremely small particle size. The smallest nanocrystals, 15 A in diameter,
      exhibit discrete optical transitions, characteristic of quantum confinement
      effects for crystalline nanocrystals with a narrow size distribution.

PMID- 11457107
TI  - Electronic and magnetic properties of alpha-Keggin anions: A DFT study of
      [XM12O40](n-), (M = W, Mo; X = Al(III), Si(IV), P(V), Fe(III), Co(II), Co(III))
      and [SiM11VO40](m- (M = Mo and W).
AB  - Calculations based on density functional theory (DFT) have been carried out to
      investigate the electronic and magnetic properties of the alpha-Keggin anions
      mentioned in the title. The atomic populations and the distribution of the
      electron density computed for the studied clusters support the hypothesis that an
      oxidized Keggin anion is an XO(4)(n-) clathrate inside a neutral M(12)O(36) cage.
      The energy gap between the band of occupied orbitals, formally delocalized over
      the oxo ligands, and the unoccupied d-metal orbitals, delocalized over the
      addenda, has been found to be independent of the central ion. However,
      substitution of a W or a Mo by V modifies the relative energy of the LUMO and
      then induces important changes in the redox properties of the cluster. In
      agreement with the most recent X-ray determination of [Co(III)W(12)O(40)](5-) and
      with the simplicity of the (183)W NMR and (17)O NMR spectra observed for this
      anion the calculations suggest that [Co(III)W(12)O(40)](5-) has a slightly
      distorted T(d ) geometry. For the parent cluster [CoW(12)O(40)](6-) the
      quadruplet corresponding to the anion encapsulating a Co(II) was found to be
      approximately 1 eV more stable than the species formed by a Co(III) and 1 e
      delocalized over the sphere of tungstens. The one-electron reduction of
      [Co(II)W(12)O(40)](6-) and [Fe(III)W(12)O(40)](5-) leads to the formation of the
      1 e blue species [Co(II)W(12)O(40)](7-) and [Fe(III)W(12)O(40)](6-). The blue
      iron cluster is considerably antiferromagnetic, and in full agreement with this
      behavior the low-spin state computed via a Broken Symmetry approach is 196 cm(-1)
      lower than the high-spin solution. In contrast, the cobalt blue anion has a low
      ferromagnetic coupling with an S-T energy gap of +20 cm(-1). This blue species is
      more stable than the alternative reduction product [Co(I)W(12)O(40)](7-) by more
      than 0.7 eV.

PMID- 11457108
TI  - Molecular dynamics simulations of the mononuclear zinc-beta-lactamase from
      Bacillus cereus.
AB  - Herein, we report molecular dynamics simulations of the mononuclear form of the
      Bacillus cereuszinc-beta-lactamase. We studied two different configurations which
      differ in the presence of a zinc-bound hydroxide or a zinc-bound water and in the
      protonation state of the essential His210 residue. Contacts of the catalytically
      important residues (Asp90, His210, Cys168, etc.) with the zinc center are
      characterized by the MD analyses. The nature of the Zn-OH(2) --> His210 proton
      transfer pathway connecting the two configurations was studied by means of QM
      calculations on cluster models while the relative stability of the two
      configurations was estimated from QM/MM calculations in the enzyme. From these
      results, a theoretical model for the kinetically active form of the B. cereus
      metalloenzyme is proposed. Some mechanistic implications and the influence of
      mutating the Cys168 residue are also discussed.

PMID- 11457109
TI  - Crystalline films of interdigitated structures formed via amidinium-carboxylate
      interactions at the air-water interface.
AB  - Electrostatic interactions between amidinium and carboxylates were used for the
      construction of interdigitated architectures at the air-solution interface.
      Spreading the water-insoluble amphiphile p-pentadecylbenzoic acid (A) on an
      aqueous solution of p-methylbenzamidinium (B) ions results in an intercalation of
      the water-soluble base between the acidic headgroups of the water-insoluble
      amphiphile to form an amorphousA-B-A-B monolayer according to grazing incidence X
      ray diffraction (GIXD) and X-ray reflectivity measurements. Upon compression the
      monolayer transforms into a crystalline film composed of three bilayers with
      interdigitated hydrocarbon chains, and a top layer whose chains are disordered.
      Water-insoluble p-heptadecylbenzamidinium spread on an aqueous solution of
      benzoic acid displays a surface pressure-area isotherm similar to that obtained
      from the above system. A mechanism that accounts for the formation of these films
      is presented. Deposition of p-heptadecylbenzamidinium and p-pentadecylbenzoic
      acid amphiphiles in a 1:1 ratio on pure water led to the formation of a
      crystalline monolayer phase but which is partially disordered. Over an aqueous
      solution containing a 1:1 mixture of benzamidinium and benzoic acid no measurable
      binding of these solute molecules to the polar headgroups of the 1:1 mixed
      monolayer could be detected by X-ray reflectivity or GIXD.

PMID- 11457110
TI  - The secondary structure of a membrane-modifying peptide in a supramolecular
      assembly studied by PELDOR and CW-ESR spectroscopies.
AB  - The new technique of pulsed electron-electron double resonance in electron spin
      echo (PELDOR) in combination with the CW-ESR method has been used to investigate
      the secondary structure of a double spin-labeled peptide (the [TOAC-1,8]-analogue
      of the peptaibol antibiotic trichogin GA IV) that is hidden into a tetrameric
      supramolecular assembly of unlabeled peptide molecules. The magnetic dipole
      dipole relaxation of spin labels has been experimentally studied in glassy
      solutions of the double-labeled peptide frozen to 77 K in a mixture of chloroform
      toluene with an excess of unlabeled peptide. The PELDOR signal oscillations have
      been observed at high degrees of dilution with unlabeled peptide. The
      intramolecular distance between the spin labels of the peptide molecule in the
      aggregate has been determined from the oscillation frequency to be 15.7 A which
      is close to the value of (approximately equal to) 14 A calculated for a 3(10)
      helical structure. Estimation of the fraction of this ordered secondary structure
      shows that about 19% of the peptide molecules in aggregates are folded in the
      3(10)-helical conformation. The present experimental results are consistent with
      our molecular model presented in J. Am. Chem. Soc. 2000, 122, 3843-3848, wherein
      four amphiphilic 3(10)-helical peptide molecules form a vesicular system with the
      polar amino acid side chains pointing to the interior, and the apolar side
      chains, to the exterior of the cluster. The experimental data were compared with
      the results obtained with other techniques.

PMID- 11457111
TI  - The electronic structure of the flavin cofactor in DNA photolyase.
AB  - Density functional theory is used to calculate the electronic structure of the
      neutral flavin radical, FADH(*), formed in the light-induced electron-transfer
      reaction of DNA repair in cis,syn-cyclobutane pyrimidine dimer photolyases. Using
      the hybrid B3LYP functional together with the double-zeta basis set EPR-II, (1)H,
      (13)C, (15)N, and (17)O isotropic and anisotropic hyperfine couplings are
      calculated and explained by reference to the electron densities of the highest
      occupied molecular orbital and of the unpaired spin distribution on the radical.
      Comparison of calculated and experimental hyperfine couplings obtained from EPR
      and ENDOR/TRIPLE resonance leads to a refined structure for the FAD cofactor in
      Escherichia coli DNA photolyase. Hydrogen bonding at N3H, O4, and N5H results in
      significant changes in the unpaired spin density distribution and hyperfine
      coupling constants. The calculated electronic structure of FADH(*) provides
      evidence for a superexchange-mediated electron transfer between the cyclobutane
      pyrimidine dimer lesion and the 7,8-dimethyl isoalloxazine moiety of the flavin
      cofactor via the adenine moiety.

PMID- 11457112
TI  - Electronic structure and properties of transition metal-benzene complexes.
AB  - A comprehensive theoretical study of the geometries, energetics, and electronic
      structure of neutral and charged 3d transition metal atoms (M) interacting with
      benzene molecules (Bz) is carried out using density functional theory and
      generalized gradient approximation for the exchange-correlation potential. The
      variation of the metal-benzene distances, dissociation energies, ionization
      potentials, electron affinities, and spin multiplicities across the 3d series in
      MBz complexes differs qualitatively from those in M(Bz)(2). For example, the
      stability of Cr(Bz)(2) is enhanced over that of CrBz by almost a factor of 30. On
      the other hand, the magnetic moment of Cr(Bz)(2) is completely quenched although
      CrBz has the highest magnetic moment, namely 6 mu(B), in the 3d metal-benzene
      series. In multidecker complexes involving V(2)(Bz)(3) and Fe(2)(Bz)(3), the
      metal atoms are found to couple antiferromagnetically. In addition, their
      dissociation energies and ionization potentials are reduced from those in
      corresponding M(Bz)(2) complexes. All of these results agree well with available
      experimental data and demonstrate the important role the organic support can play
      on the properties of metal atoms/clusters.

PMID- 11457113
TI  - Phase-transfer catalyst-induced changes in the absorption and fluorescence
      behavior of some electron donor-acceptor molecules.
AB  - The quaternary ammonium salts find extensive use in a variety of chemical
      applications as surfactants and phase-transfer catalysts. Even though the
      interaction of the surfactants with various systems has been studied rather
      extensively, very little information is available on how the phase-transfer
      catalysts (PTC) interact with the dipolar systems in nonpolar media and
      how/whether these solubilizing agents affect the properties of the dissolved
      molecules. In this paper, the interaction of several tetraalkylammonium salts,
      commonly used as PTC, with a number of electron donor-acceptor (EDA) systems has
      been studied by absorption and fluorescence spectroscopy. The phase-transfer
      catalysts have been found to affect both the absorption and fluorescence
      properties of the EDA systems. The spectral changes of the EDA molecules induced
      by the tetraalkylammonium salts suggest the formation of an 1:1 complex between
      the two in nonpolar media. An electrostatic interaction between the phase
      transfer catalysts (which exist as ion pairs in nonpolar media) and the dipolar
      molecules is shown to be the driving force for the formation of the complex. The
      dependence of the formation constant of the complex on the polarity of the media
      suggests a charge-transfer nature of the complex. It is shown that the anionic
      component of the salts serves as a source of electron to the positive end of the
      dipolar molecule, while the tetraalkylammonium cation, besides helping
      solubilization of its anionic counterpart in the nonpolar media, serves
      neutralizing the negative charge at the acceptor end of the EDA molecule. In
      effect, a cooperative influence of the cationic and anionic components of the PTC
      enhances the charge separation within the dipolar fluorophores. On the basis of
      the PTC-induced changes in the photophysical behavior of the EDA molecules, a
      possible structure for the 1:1 complex has been proposed. It has been concluded
      that a phase-transfer catalyst should not be treated as an innocuous substance
      that merely helps transfer of a polar substance from a polar to a nonpolar
      environment. Instead, it is demonstrated that the association of a PTC with a
      dipolar species can significantly change various properties of the latter.

PMID- 11457114
TI  - A nano-scale barrel and cube: transition metal-mediated self-assembly of CpCoCb
      derived ligand scaffolds.

PMID- 11457115
TI  - Characterization of surface organometallic complexes using high resolution 2D
      solid-state NMR spectroscopy. Application to the full characterization of a
      silica supported metal carbyne: (triple bond)SiO-Mo((triple bond)C-Bu-t)(CH(2)-Bu
      t)(2).

PMID- 11457116
TI  - Multiple hydrogen/lithium interconversions at the same benzene nucleus: two at
      the most.

PMID- 11457117
TI  - The role of the leaving group in the dissociation of radical anions of 9
      (aryloxymethyl)anthracenes.

PMID- 11457118
TI  - A Ti(2)Ru(2)Pd(2) oxo-sulfido cluster synthesized by linking two rationally
      preorganized TiRuPdS(2) heterotrimetallic units with an oxo ligand: its reaction
      with an alkyne.

PMID- 11457120
TI  - Highly enantioselective hetero-Diels-Alder reactions catalyzed by a C(2)
      symmetric bis(sulfoximine) copper(II) complex.

PMID- 11457119
TI  - A capable bridging ligand for Fe-only hydrogenase: density functional
      calculations of a low-energy route for heterolytic cleavage and formation of
      dihydrogen.

PMID- 11457121
TI  - Oxidation of isoniazid by manganese and Mycobacterium tuberculosis catalase
      peroxidase yields a new mechanism of activation.

PMID- 11457122
TI  - Validity of using the radius of gyration as a restraint in NMR protein structure
      determination.

PMID- 11457123
TI  - Activation of the C-H bond of methane by intermediate Q of methane monooxygenase:
      a theoretical study.

PMID- 11457124
TI  - Noncovalent sidewall functionalization of single-walled carbon nanotubes for
      protein immobilization.

PMID- 11457125
TI  - Novel class of morphinans with acrylonitrile incorporated substructures as key
      intermediates for non-oxygen-bridged opioid ligands.

PMID- 11457126
TI  - Electron transfer initiated cyclizations: cyclic acetal synthesis through carbon
      carbon sigma-bond activation.

PMID- 11457127
TI  - Protein side-chain rotamers from dipolar couplings in a liquid crystalline phase.

PMID- 11457128
TI  - Synthesis and size control of gold nanoparticles stabilized by
      poly(methylphenylphosphazene).

PMID- 11457130
TI  - Generation of highly enantioselective catalysts from the pseudoenatiomeric
      assembly of BINOL, F(8)BINOL, and Ti(OiPr)(4).

PMID- 11457129
TI  - Tag-reporter strategy for facile oligosaccharide synthesis on polymer support.

PMID- 11457131
TI  - Oxidation of TTF derivatives using (diacetoxyiodo)benzene: a general chemical
      route toward cation radicals, dications, and nonstoichiometric salts.

PMID- 11457132
TI  - Helical rosette nanotubes: design, self-assembly, and characterization.

PMID- 11457134
TI  - Complexation of unsaturated carbon-carbon bonds in pi-conjugated polymers with
      transition metals.
AB  - The present paper explores the possibility of preparing pi-conjugated
      organometallic polymer hybrid systems based on a poly(p-phenylene ethynylene)
      (PPE) derivative, in which the ethynylene moieties of the polymer are coordinated
      to platinum(II) centers. The use of the "bifunctional" [Pt-(mu
      Cl)Cl(PhCH=CH(2))](2) (2) allows, under appropriate conditions, the formation of
      three-dimensionally cross-linked, conjugated PPE-platinum(II) networks. The
      synthesis of [Pt-(mu-Cl)Cl(PhC(triple bond)CPh)](2), as a model compound, and a
      series of model reactions of 2 with diphenylacetylene (3) have enabled an NMR
      study which has revealed a number of equilibria, and suggests a mixed Pt-styrene
      acetylene complex as a key structure. As expected, the coordination of Pt
      markedly influences the photophysical characteristics of the PPE. The
      photoluminescence is efficiently quenched, and the absorption maximum in the
      visible regime experiences a hypsochromic shift upon complexation with 2.

PMID- 11457135
TI  - Perchlorophenalenyl radical.
AB  - We report the preparation and solid-state characterization of the
      perchlorophenalenyl radical (1). The radical is initially obtained as a yellow
      green solid by reduction of the perchlorophenalenium salt (12(+)). This solid
      sublimes in a sealed tube to give black shiny hexagonal crystals of the
      perchlorophenalenyl radical (1). The structure consists of 1-dimensional stacks
      of the monomeric radical. The peri-chlorine atoms force the phenalenyl system to
      be strongly nonplanar leading to a large separation between adjacent molecules
      within the stacks (3.78 A), and the molecules adopt two distinct stacking motifs
      (quasisuperimposed and rotated by 60 degrees with respect to neighbors). Because
      of the packing frustration in the lattice and the large intermolecular spacing,
      the solid shows Curie paramagnetism in the temperature range 100-400 K, before
      antiferromagnetic coupling sets in at low temperatures. Due to the narrow
      bandwidth that results from the isolation of the individual molecules, the solid
      is a Mott-Hubbard insulator, with a room-temperature conductivity of rho(RT) =
      10(-10) S/cm.

PMID- 11457136
TI  - A self-assembled homooxacalix[3]arene-based dimeric capsule constructed by a
      Pd(II)-pyridine interaction which shows a novel chiral twisting motion in
      response to guest inclusion.
AB  - A capsule-like molecule was constructed by dimerization of pyridine-containing
      homooxacalix[3]aryl esters utilizing a Pd(II)-pyridine interaction when Li(+)
      ions were bound to the ionophoric lower rims. (1)H NMR spectral studies showed
      that the self-assembled molecular capsule 3b.(Li(+))(2) has a highly symmetrical
      D(3)(h)-structure. It was also found that this self-assembled molecular system
      can form capsular structures in the presence of Na(+) or ammonium (RNH(3)(+))
      ions. Very interestingly, these molecular capsules are twisted into triply
      bridged helical structures, and chiral RNH(3)(+) guests included in the cavity
      induce a change in the (P) versus (M) ratio, resulting in high chiral induction (
      approximately 70%). These results indicate that the self-assembled molecular
      capsule 3b has a novel chiral factor in which the (P) versus (M) equilibrium is
      readily controllable by the inclusion of chiral guest molecules.

PMID- 11457137
TI  - Highly regioselective anaerobic photocyclization of 3-styrylpyridines.
AB  - The photochemical behavior of the cis isomers of the three isomeric
      styrylpyridines and two (aminostyryl)pyridines has been investigated under
      aerobic and anaerobic conditions. Both 3-styrylpyridine and its 3'-amino
      derivative undergo highly regioselective formation of 2-azaphenanthrene products
      under anaerobic conditions. In the presence of oxygen, mixtures of 4- and 2
      azaphenanthrene products are obtained. The formation of 2-azaphenanthrenes in the
      absence of oxygen is attributed to conversion of the 4a,4b-dihydroazaphenanthrene
      primary photoproduct to a 1,4-dihydropyridine intermediate by means of a formal
      1,7-hydrogen shift. This intermediate is moderately stable in the absence of
      oxygen and has been characterized by comparison of its (1)H NMR and electronic
      absorption spectra with calculated spectra. This intermediate is converted to the
      2-azaphenanthrene in both the absence and presence of oxygen. The
      regioselectivity of photocyclization of 3-substituted stilbenes and related
      diarylethylenes is suggested to depend on the relative rate constants for ring
      opening and sigmatropic rearrangements of the dihydrophenanthrene intermediates
      as well as their rates of reaction with oxygen or other oxidants.

PMID- 11457138
TI  - Oligomerization of uniquely folded mini-protein motifs: development of a
      homotrimeric betabetaalpha peptide.
AB  - The discovery of a discretely folded homotrimeric betabetaalpha motif (BBAT1) was
      recently reported (J. Am. Chem. Soc. 2001, 123, 1002-1003). Herein the design,
      synthesis, and analysis of a small library of peptides which led to the isolation
      of BBAT1 is described. betabetaalpha peptides based on the monomeric sequence of
      BBA5 (Folding Des. 1998, 120, 95-103) were synthesized to include the anthranilic
      acid/nitrotyrosine fluorescence quenching pair to rapidly detect interpeptide
      association. In the first generation of peptides synthesized, truncations in the
      loop region connecting the beta-hairpin to the alpha-helix revealed that a two
      residue deletion in the loop promoted an interpeptide association as detected by
      fluorescence quenching. An additional library of 22 loop-truncated betabetaalpha
      peptides was subsequently synthesized to include a variety of sequence mutations
      in an effort to enhance the observed peptide-peptide binding. From the
      fluorescence quenching screen, peptide B2 was found to possess the strongest
      fluorescence-quenching response, indicative of a strong peptide-peptide
      association. Due the poor solubility of peptide B2, the S-methylated cysteine at
      position 9 in the loop was substituted with a glycine to generate peptide BBAT1
      which possessed greatly improved water solubility and formed discrete trimers.
      The successful design of this oligomeric betabetaalpha structure will likely aid
      the design of more complex alpha-beta superstructures and further our
      understanding of the factors controlling protein-protein interactions at alpha
      beta protein interfaces.

PMID- 11457139
TI  - The potent anti-HIV protein cyanovirin-N contains two novel carbohydrate binding
      sites that selectively bind to Man(8) D1D3 and Man(9) with nanomolar affinity:
      implications for binding to the HIV envelope protein gp120.
AB  - Cyanovirin-N (CVN) is a monomeric 11 kDa cyanobacterial protein that potently
      inactivates diverse strains of human immunodeficiency virus (HIV) at the level of
      cell fusion by virtue of high affinity interactions with the surface envelope
      glycoprotein gp120. Several lines of evidence have suggested that CVN-gp120
      interactions are in part mediated by N-linked complex carbohydrates present on
      gp120, but experimental evidence has been lacking. To this end we screened a
      comprehensive panel of carbohydrates which represent structurally the N-linked
      carbohydrates found on gp120 for their ability to inhibit the fusion-blocking
      activity of CVN in a quantitative HIV-1 envelope-mediated cell fusion assay. Our
      results show that CVN specifically recognizes with nanomolar affinity
      Man(9)GlcNAc(2) and the D1D3 isomer of Man(8)GlcNAc(2). Nonlinear least squares
      best fitting of titration data generated using the cell fusion assay show that
      CVN binds to gp120 with an equilibrium association constant (K(a)) of 2.4 (+/-
      0.1) x 10(7) M(-1) and an apparent stoichiometry of 2 equiv of CVN per gp120,
      Man(8)GlcNAc(2) D1D3 acts as a divalent ligand (2 CVN:1 Man(8)) with a K(a) of
      5.4 (+/- 0.5) x 10(7) M(-1), and Man(9)GlcNAc(2) functions as a trivalent ligand
      (3 CVN:1 Man(9)) with a K(a) of 1.3 (+/- 0.3) x 10(8) M(-1). Isothermal titration
      calorimetry experiments of CVN binding to Man(9)GlcNAc(2) at micromolar
      concentrations confirmed the nanomolar affinity (K(a) = 1.5 (+/- 0.9) x 10(8) M(
      1)), and the fitted data indicated a stoichiometry equal to approximately one (1
      Man(9):1 CVN). The 1:1 stoichiometry at micromolar concentrations suggested that
      CVN has not only a high affinity binding site-relevant to the studies at nM
      concentrations-but a lower affinity site as well that facilitates cross-linking
      of CVN-oligomannose at micromolar concentrations or higher. The specificity of
      CVN for Man(8) D1D3 and Man(9) over the D1D2 isomer of Man(8) indicated that the
      minimum structure required for high affinity binding comprises Manalpha1 -->
      2Manalpha. By following the (1)H-(15)N correlation spectrum of (15)N-labeled CVN
      upon titration with this disaccharide, we unambiguously demonstrate that CVN
      recognizes and binds to the disaccharide Manalpha1 --> 2Manalpha via two distinct
      binding sites of differing affinities located on opposite ends of the protein.
      The high affinity site has a K(a) of 7.2 (+/- 4) x 10(6) M(-1) and the low
      affinity site a K(a) of 6.8 (+/- 4) x 10(5) M(-1) as determined by isothermal
      titration calorimetry. Mapped surfaces of the carbohydrate binding sites are
      presented, and implications for binding to gp120 are discussed.

PMID- 11457140
TI  - Improving the accuracy of NMR structures of DNA by means of a database potential
      of mean force describing base-base positional interactions.
AB  - NMR structure determination of nucleic acids presents an intrinsically difficult
      problem since the density of short interproton distance contacts is relatively
      low and limited to adjacent base pairs. Although residual dipolar couplings
      provide orientational information that is clearly helpful, they do not provide
      translational information of either a short-range (with the exception of proton
      proton dipolar couplings) or long-range nature. As a consequence, the description
      of the nonbonded contacts has a major impact on the structures of nucleic acids
      generated from NMR data. In this paper, we describe the derivation of a potential
      of mean force derived from all high-resolution (2 A or better) DNA crystal
      structures available in the Nucleic Acid Database (NDB) as of May 2000 that
      provides a statistical description, in simple geometric terms, of the relative
      positions of pairs of neighboring bases (both intra- and interstrand) in
      Cartesian space. The purpose of this pseudopotential, which we term a DELPHIC
      base-base positioning potential, is to bias sampling during simulated annealing
      refinement to physically reasonable regions of conformational space within the
      range of possibilities that are consistent with the experimental NMR restraints.
      We illustrate the application of the DELPHIC base-base positioning potential to
      the structure refinement of a DNA dodecamer, d(CGCGAATTCGCG)(2), for which NOE
      and dipolar coupling data have been measured in solution and for which crystal
      structures have been determined. We demonstrate by cross-validation against
      independent NMR observables (that is, both residual dipolar couplings and NOE
      derived intereproton distance restraints) that the DELPHIC base-base positioning
      potential results in a significant increase in accuracy and obviates artifactual
      distortions in the structures arising from the limitations of conventional
      descriptions of the nonbonded contacts in terms of either Lennard-Jones van der
      Waals and electrostatic potentials or a simple van der Waals repulsion potential.
      We also demonstrate, using experimental NMR data for a complex of the male sex
      determining factor SRY with a duplex DNA 14mer, which includes a region of highly
      unusual and distorted DNA, that the DELPHIC base-base positioning potential does
      not in any way hinder unusual interactions and conformations from being
      satisfactorily sampled and reproduced. We expect that the methodology described
      in this paper for DNA can be equally applied to RNA, as well as side chain-side
      chain interactions in proteins and protein-protein complexes, and side chain
      nucleic acid interactions in protein-nucleic acid complexes. Further, this
      approach should be useful not only for NMR structure determination but also for
      refinement of low-resolution (3-3.5 A) X-ray data.

PMID- 11457141
TI  - Pseudopolymorphism in tetradeca-2,6-O-methyl-beta-cyclodextrin: the crystal
      structures for two new hydrates-conformational variability in the alkylated beta
      cyclodextrin molecule.
AB  - Tetradeca-2,6-O-methyl-beta-cyclodextrin, per-2,6-OMe-beta-CD, is an unusual beta
      cyclodextrin, beta-CD, derivative because it has a negative thermal solubility
      coefficient in aqueous solution. This report describes two new crystal structures
      for hydrates of per-2,6-OMe-beta-CD crystallized at different temperatures: per
      2,6-OMe-beta-CD.1.08H(2)O crystallized at 50 degrees C and per-2,6-OMe-beta
      CD.14.7H(2)O crystallized at 4 degrees C. The crystal structure for per-2,6-OMe
      beta-CD.1.08H(2)O reveals conformational flexibility in the methylated beta-CD
      molecule; two adjacent glucose residues are disordered as a result of their
      adopting different tilts with respect to the O(4) plane characterizing the
      molecule. When one conformation is present there is a water molecule in the
      lattice (0.5 population parameter); said water is displaced by the methyl of a
      methoxy substituent when the other conformer is present.

PMID- 11457142
TI  - New fluorogenic probes for oxygen and carbene transfer: a sensitive assay for
      single bead-supported catalysts.
AB  - A high-throughput screening assay for atom transfer catalysis has been developed.
      This assay is based on two probes, developed herein, which generate highly
      fluorescent products upon carbene or oxygen atom transfer. The emission
      wavelength of probes 1 and 5 shift significantly (up to 90 nm) upon epoxidation,
      allowing detection of product at 3% conversion. Probe 7 is not fluorescent, while
      fluorescence emission by carbene insertion/rearrangement product 8 allows
      detection at less than 1% conversion. Such sensitivity allows for examination of
      single-bead reactions in a high throughput array format (1536 wells per plate),
      and provides a broad detection window ranging from single to high turnover
      numbers. Thousands of metal complexes are evaluated in a single screening
      experiment. Preliminary screening of a diverse ligand library with probe 7 in the
      presence of Rh(II) uncovered new catalysts capable of cyclopropanation and C-H
      insertion.

PMID- 11457143
TI  - On the negligible impact of ruffling on the electronic spectra of porphine,
      tetramethylporphyrin, and perfluoroalkylporphyrins.
AB  - In the first part of this paper, the syntheses, structural characterization,
      molecular modeling, and electronic spectra for planar and nonplanar
      perfluoroalkylated porphyrins, (R(f))(4)P's, are reported. These studies
      demonstrate that the intrinsic substituent effect of the perfluoroalkyl group on
      the long-wavelength electronic spectrum of porphyrins is substantial, and similar
      (in magnitude) to that of a phenyl ring. Moreover, it is shown that out-of-plane
      distortion of (R(f))(4)P's has a negligible impact on their electronic spectra.
      These data bolster the findings of our earlier work and demonstrate that
      nonplanarity of (R(f))(4)P's does not result in a red-shift in their optical
      spectra. In the second part of this paper, time-dependent density functional
      spectral calculations (B3LYP/6-311G/TD) for porphine, 5,10,15,20
      tetrakis(trifluoromethyl)porphyrin, and 5,10,15,20-tetramethylporphyrin in a
      variety of ruffled conformations are reported. The results of these studies
      indicate that (1) substantial ruffling of porphyrins has a negligible effect upon
      their electronic spectra, (2) similarly small effects upon electronic spectra are
      predicted if electron-withdrawing or electron-releasing groups decorate the
      porphyrin periphery, (3) for sterically encumbered porphyrins, ruffling can
      actually result in hypsochromic shifts in various absorption bands, and (4) the
      bulk of the red-shift commonly thought to be due to nonplanar distortion actually
      arises from other substituent effects. These results pose serious challenges to
      previous theoretical and empirical studies that have sought to find a cause-and
      effect relationship between nonplanarity and electronic spectra in porphyrins.

PMID- 11457144
TI  - Supramolecular chemistry: molecular recognition and self-assembly using rigid
      spacer-chelators bearing cofacial terpyridyl palladium(II) complexes separated by
      7 A.
AB  - Partially and fully aromatic molecular spacers bearing two symmetrically bound
      terpyridyl chelators have been prepared. These spacer-chelators were constructed
      to dispose the two terpyridyl ligands and their complexes with square planar
      metals cofacially with a separation of about 7 A between the two metals.
      Dipalladium(II) complexes of these spacer-chelators were prepared and
      characterized. These palladium complexes readily form large molecular rectangles
      with a linear linker such as 4,4'-dipyridyl. The dichlorodipalladium complex of
      the partially reduced spacer-chelator is capable of incarcerating planar aromatic
      and coordination compounds as guests. A crystal structure showing the
      incorporation of 9-methylanthracene has been determined. A 9-methylanthracene
      lies completely within the approximately 7 A space provided by the cleft formed
      by the two cofacially disposed chloro-palladium-terpyridyl units. The crystal
      structure shows additional pi-stacking interactions between a second 9
      methylanthracene and neighboring receptors.

PMID- 11457145
TI  - Analysis of slow interdomain motion of macromolecules using NMR relaxation data.
AB  - The interpretation of NMR relaxation data for macromolecules possessing slow
      interdomain motions is considered. It is shown how the "extended model-free
      approach" can be used to analyze (15)N backbone relaxation data acquired at three
      different field strengths for Xenopus Ca(2+)-ligated calmodulin. This protein is
      comprised of two domains connected by two rigid helices joined by a flexible
      segment. It is possible to uniquely determine all "extended model-free"
      parameters without any a priori assumptions regarding their magnitudes by
      simultaneously least-squares fitting the relaxation data measured at two
      different magnetic fields. It is found that the two connecting helices (and
      consequently the domains) undergo slow motions relative to the conformation in
      which the two helices are parallel. The time scales and amplitudes of these
      "wobbling" motions are characterized by effective correlation times and squared
      order parameters of approximately 3 ns and 0.7, respectively. These values are
      consistent with independent estimates indicating that this procedure provides a
      useful first-order description of complex internal motions in macromolecules
      despite neglecting the coupling of overall and interdomain motions.

PMID- 11457146
TI  - New mode of coordination for the dinitrogen ligand: formation, bonding, and
      reactivity of a tantalum complex with a bridging N(2) unit that is both side-on
      and end-on.
AB  - The reaction of a mixture of 1 equiv of PhPH(2) and 2 equiv of PhNHSiMe(2)CH(2)Cl
      with 4 equiv of Bu(n)Li followed by the addition of THF generates the lithiated
      ligand precursor [NPN]Li(2).(THF)(2) (where [NPN] = PhP(CH(2)SiMe(2)NPh)(2)). The
      reaction of [NPN]Li(2).(THF)(2) with TaMe(3)Cl(2) produces [NPN]TaMe(3), which
      reacts under H(2) to yield the diamagnetic dinuclear Ta(IV) tetrahydride
      ([NPN]Ta)(2)(mu-H)(4). This hydride reacts with N(2) with the loss of H(2) to
      produce ([NPN]Ta(mu-H))(2)(mu-eta(1):eta(2)-N(2)), which was characterized both
      in solution and in the solid state, and contains strongly activated N(2) bound in
      the unprecedented side-on end-on dinuclear bonding mode. A density functional
      theory calculation on the model complex [(H(3)P)(H(2)N)(2)Ta(mu-H)](2)(mu
      eta(1):eta(2)-N(2)) provides insight into the molecular orbital interactions
      involved in the side-on end-on bonding mode of dinitrogen. The reaction of
      ([NPN]Ta(mu-H))(2)(mu-eta(1):eta(2)-N(2)) with propene generates the end-on bound
      dinitrogen complex ([NPN]Ta(CH(2)CH(2)CH(3)))(2)(mu-eta(1):eta(1)-N(2)), and the
      reaction of [NPN]Li(2).(THF)(2) with NbCl(3)(DME) generates the end-on bound
      dinitrogen complex ([NPN]NbCl)(2)(mu-eta(1):eta(1)-N(2)). These two end-on bound
      dinitrogen complexes provide evidence that the bridging hydride ligands are
      responsible for the unusual bonding mode of dinitrogen in ([NPN]Ta(mu-H))(2)(mu
      eta(1):eta(2)-N(2)). The dinitrogen moiety in the side-on end-on mode is amenable
      to functionalization; the reaction of ([NPN]Ta(mu-H))(2)(mu-eta(1):eta(2)-N(2))
      with PhCH(2)Br results in C-N bond formation to yield [NPN]Ta(mu-eta(1):eta(2)
      N(2)CH(2)Ph)(mu-H)(2)TaBr[NPN]. Nitrogen-15 NMR spectral data are provided for
      all the tantalum-dinitrogen complexes and derivatives described.

PMID- 11457147
TI  - New insight on the origin of the unusual acidity of Meldrum's acid from ab initio
      and combined QM/MM simulation study.
AB  - Ab initio molecular orbital and combined QM/MM Monte Carlo simulations have been
      carried out to investigate the origin of the unusually high acidity of Meldrum's
      acid. Traditionally, the high acidity of Meldrum's acid relative to that of
      methyl malonate has been attributed to an additive effect due to the presence of
      two E esters in the dilactone system. However, the present study reveals that
      there is significant nonadditive effect that also makes major contributions. This
      results from preferential stabilization of the enolate anion over that of
      Meldrum's acid due to anomeric stereoelectronic interactions. To investigate
      solvent effects on the acidity in aqueous solution, the relative acidities of Z
      and E conformers of methyl acetate have been determined in combined ab initio
      QM/MM simulations. There is significant solvent effect on the conformational
      equilibria for both the neutral ester and its enolate anion in water, leading to
      stabilization of the E stereoisomer. However, the computed solvent effect of 4.4
      kcal/mol in favor of the E isomer of methyl acetate is largely offset by the
      favorable solvation of 3.4 kcal/mol for the E conformer of the enolate anion.
      This leads to an enhanced acidity of 3.4 kcal/mol for the (E)-methyl acetate in
      water over the Z conformer. In Meldrum's acid, it is the preferential
      stabilization of the enolate anion due to anomeric effects coupled with the
      intrinsically higher acidity of the E conformation of ester that is responsible
      for its high acidity.

PMID- 11457148
TI  - The reaction of protonated dimethyl ether with dimethyl ether: temperature and
      isotope effects on the methyl cation transfer reaction forming trimethyloxonium
      cation and methanol.
AB  - Fourier transform ion cyclotron resonance mass spectrometry has been used to
      study the temperature and deuterium isotope effects on the methyl cation transfer
      reaction between protonated dimethyl ether and dimethyl ether to produce
      trimethyloxonium cation and methanol. From the temperature dependence of this
      bimolecular reaction it was possible to obtain thermodynamic information
      concerning the energy barrier for methyl cation transfer for the first time. From
      the slope of an Arrhenius plot, a value for DeltaH(++) of -1.1 +/- 1.2 kJ mol(-1)
      was obtained, while from the intercept a value for DeltaS(++) of -116 +/- 15 J K(
      1) mol(-1) was derived. This yields a DeltaG(++)(298) value of 33.7 +/- 2.1 kJ
      mol(-1). All thermodynamic values were in good agreement with ab initio
      calculations. Rate constant ratios for the unimolecular dissociation forming
      trimethyloxonium cation and the dissociation re-forming reactants were extracted
      from the apparent bimolecular rate constant. Attempts at modeling the temperature
      dependence and isotope effects of the unimolecular dissociation forming
      trimethyloxonium cation were also made.

PMID- 11457149
TI  - An analysis of the interactions between the Sem-5 SH3 domain and its ligands
      using molecular dynamics, free energy calculations, and sequence analysis.
AB  - The Src-homology-3 (SH3) domain of the Caenorhabditis elegans protein Sem-5 binds
      proline-rich sequences. It is reported that the SH3 domains broadly accept amide
      N-substituted residues instead of only recognizing prolines on the basis of side
      chain shape or rigidity. We have studied the interactions between Sem-5 and its
      ligands using molecular dynamics (MD), free energy calculations, and sequence
      analysis. Relative binding free energies, estimated by a method called MM/PBSA,
      between different substitutions at sites -1, 0, and +2 of the peptide are
      consistent with the experimental data. A new method to calculate atomic partial
      charges, AM1-BCC method, is also used in the binding free energy calculations for
      different N-substitutions at site -1. The results are very similar to those
      obtained from widely used RESP charges in the AMBER force field. AM1-BCC charges
      can be calculated more rapidly for any organic molecule than can the RESP
      charges. Therefore, their use can enable a broader and more efficient application
      of the MM/PBSA method in drug design. Examination of each component of the free
      energy leads to the construction of van der Waals interaction energy profiles for
      each ligand as well as for wild-type and mutant Sem-5 proteins. The profiles and
      free energy calculations indicate that the van der Waals interactions between the
      ligands and the receptor determine whether an N- or a Calpha-substituted residue
      is favored at each site. A VC value (defined as a product of the conservation
      percentage of each residue and its van der Waals interaction energy with the
      ligand) is used to identify several residues on the receptor that are critical
      for specificity and binding affinity. This VC value may have a potential use in
      identifying crucial residues for any ligand-protein or protein-protein system.
      Mutations at two of those crucial residues, N190 and N206, are examined. One
      mutation, N190I, is predicted to reduce the selectivity of the N-substituted
      residue at site -1 of the ligand and is shown to bind similarly with N- and
      Calpha-substituted residues at that site.

PMID- 11457150
TI  - A theoretical study of the primary oxo transfer reaction of a dioxo
      molybdenum(VI) compound with imine thiolate chelating ligands: a molybdenum
      oxotransferase analogue.
AB  - The reaction mechanism of an analogue system of the molybdenum oxotransferases
      was investigated at the density functional (B3P86) level of theory. Kinetic
      measurements by Schultz and Holm suggest that the reaction MoO(2)(t-BuL-NS)(2) +
      X --> MoO(t-BuL-NS)(2) + OX (t-BuL-NS = bis(4-tert-butylphenyl)-2
      pyridylmethanethiolate(1-)) occurs through an associative transition state. Our
      results on the model reaction, MoO(2)(SCH(2)CHNH)(2) + P(CH(3))(3) -->
      MoO(SCH(2)CHNH)(2) + OP(CH(3))(3), support this hypothesis, and indicate that
      this reaction proceeds through a two-step mechanism via an associative
      intermediate. The DeltaH(++) for the first, and rate-determining, step was
      predicted to be 9.4 kcal/mol, and DeltaH(++) for the second step (release of the
      OP(CH(3))(3) product) was predicted to be 3.3 kcal/mol. These results are in good
      agreement with the experimental system, for which the rate determining DeltaH(++)
      = 9.6(6) kcal/mol. Shultz and Holm's experimental model undergoes a significant
      ligand rearrangement in the oxo transfer reaction: the reactant, MoO(2)(t-BuL
      NS)(2), has a trans-S arrangement of the ligands, while the product, MoO(t-BuL
      NS)(2), has a trans-N arrangement. To investigate the driving force behind the
      ligand rearrangement, four model compounds, that systematically removed the
      unsaturation at the N and the chelate character of the ligands, were modeled at
      the B3P86 level of theory. For all models of the dioxo species, the trans-N
      isomer was higher in energy than the trans-S isomer. The analysis of these
      results indicated that a trans influence accounts for approximately 16% of the
      energy difference, the unsaturation at the nitrogens accounts for approximately
      26%, and the ring strain from the chelator accounts for approximately 58% of the
      energy difference between the two isomers (trans-N and trans-S). For all models
      of the monooxo species, only the trans-N species was a stable geometry.
      Therefore, for the reverse oxo transfer reaction, ligand rearrangement must occur
      after or during the attack of the OX substrate.

PMID- 11457151
TI  - Relocalization in floppy free radicals: the OCNO and OCCHO isoelectronic series.
AB  - A survey of the XCNY and XCCHY radicals with X and Y = CH(2), NH, and O has been
      carried out by ab initio QCISD/6-311G(d,p) calculations to assess the impact of
      low-lying excited electronic states on the molecular dynamics. Multiple canonical
      structures may be drawn for each of these structural formulas, with the principal
      competition for most stable configuration between a (2)A' form with four
      electrons in a" orbitals and a (2)A" form with five a" electrons. Other low-lying
      configurations may include a 5a" state with nominally pentavalent nitrogen and a
      6a" state. Optimized geometries and harmonic frequencies were evaluated for the
      lowest-energy minima on the potential energy surfaces. Localized unpaired
      electron density causes the 4a" state to be the most stable for (NH)CCHO and
      OCCHY, whereas allylic resonance stabilization favors the 5a" state for all other
      radicals in the set. For five of the 18 molecules studied, secondary minima
      (excluding conformers) are found within 30 kJ mol(-)(1) of the most stable state
      at the QCISD/6-311G(d,p) level, suggesting that photolysis or pyrolysis of parent
      compounds may result in multiple isomers of the resulting reactive intermediates.
      Predicted equilibrium geometries, approximate thermochemical quantities for
      dissociation of the central bond, and selected spectroscopic parameters are
      presented for all 18 structural formulas. Convergence tests were also performed
      for the glyoxallyl radical (OCCHO) to resolve discrepancies between single- and
      multireference post-SCF results. These tests find that extension of the MCSCF
      methods to include sigma bonding orbitals or virtual-orbital CI brings MCSCF
      relative energies into agreement with results from standard single-reference CI
      and CC methods. Relative configurational energies evaluated at Hartree-Fock
      levels routinely differ from post-SCF values by 30 kJ mol(-1) or more.

PMID- 11457152
TI  - A DFT study of the interresidue dependencies of scalar J-coupling and magnetic
      shielding in the hydrogen-bonding regions of a DNA triplex.
AB  - Scalar coupling constants and magnetic shieldings in the imino hydrogen-bonding
      region of Hoogsteen-Watson-Crick T.A-T and C(+).G-C triplets have been calculated
      as a function of the distance between proton donor and acceptor nitrogen atoms.
      The Fermi contact contributions to (h2)J((15)N-H...(15)N), (1)J((15)N-(1)H), and
      (h1)J((1)H...(15)N) were computed using density functional theory/finite
      perturbation theory (DFT/FPT) methods for the full base triplets at the
      unrestricted B3PW91/6-311G level. Chemical shifts delta((1)H) and delta((15)N)
      were obtained at the same level using the gauge including atomic orbital (GIAO)
      method for magnetic shielding. All three scalar couplings and all three chemical
      shifts are strongly interrelated and exhibit monotonic changes with base pair
      separation. These correlations are in conformity with experimental data for a 32
      nucleotide DNA triplex. The results suggest that both chemical shifts and
      coupling constants can be used to gain information on H-bond donor-acceptor
      distances in nucleic acids. In addition to the DFT/FPT calculations, a simple
      three-orbital model of the N-H...H bond and a sum-over-states analysis is
      presented. This model reproduces the basic features of the H-bond coupling
      effect. In accordance with this model and the DFT calculations, a positive sign
      for the (h2)J(NN) coupling is determined from an E.COSY experiment.

PMID- 11457153
TI  - Electron affinities of the DNA and RNA bases.
AB  - Adiabatic electron affinities (AEAs) for the DNA and RNA bases are predicted by
      using a range of density functionals with a double-zeta plus polarization plus
      diffuse (DZP++) basis set in an effort to bracket the true EAs. Although the AEAs
      exhibit moderate fluctuations with respect to the choice of functional,
      systematic trends show that the covalent uracil (U) and thymine (T) anions are
      bound by 0.05-0.25 eV while the adenine (A) anion is clearly unbound. The
      computed AEAs for cytosine (C) and guanine (G) oscillate between small positive
      and negative values for the three most reliable functional combinations (BP86,
      B3LYP, and BLYP), and it remains unclear if either covalent anion is bound. AEAs
      with B3LYP/TZ2P++ single points are 0.19 (U), 0.16 (T), 0.07 (G), -0.02 (C), and 
      0.17 eV (A). Favorable comparisons are made to experimental estimates
      extrapolated from photoelectron spectra data for the complexes of the nucleobases
      with water. However, experimental values scaled from liquid-phase reduction
      potentials are shown to overestimate the AEAs by as much as 1.5 eV. Because the
      uracil and thymine covalent EAs are in energy ranges near those of their dipole
      bound counterparts, preparation and precise experimental measurement of the
      thermodynamically stable covalent anions may prove challenging.

PMID- 11457154
TI  - Kinetic and density functional studies on alkyl-carbene elimination from Pd(II)
      heterocylic carbene complexes: a new type of reductive elimination with clear
      implications for catalysis.
AB  - A number of new methyl-Pd(II) complexes of heterocyclic carbenes of the form
      [PdMe(tmiy)L(2)]BF(4) have been prepared, and their reaction behavior has been
      studied (tmiy = 1,3,4,5-tetramethylimidazolin-2-ylidene, L = cyclooctadiene (8),
      methyldiphenylphosphine (9), triphenyl phosphite (10), triphenylphosphine (11)).
      In common with other hydrocarbyl-M carbene complexes (M = Pd, Ni) the complexes
      are predisposed to a facile decomposition process. A detailed mechanism for the
      process and of the decomposition pathway followed is presented herein. All
      complexes decompose with first-order kinetics to yield 1,2,3,4,5
      pentamethylimidazolium tetrafluoroborate and Pd(0) species. The kinetic
      investigations combined with density functional studies show that the complexes
      decompose via a mechanism of concerted reductive elimination of the methyl group
      and carbene. The reaction represents a new type of reductive elimination from
      transition metals and also represents a low-energy pathway to catalyst
      deactivation for catalysts based on heterocyclic carbenes. The theoretical
      studies indicate extensive involvement of the p(pi) orbital on the carbene carbon
      in the transition structure. Methods of stabilizing catalysts based on
      heterocyclic carbene complexes are suggested, and the possibility of involvement
      of carbene species during catalysis in ionic liquids is discussed.

PMID- 11457155
TI  - Dimeric phenalenyl-based neutral radical molecular conductors.
AB  - We report the preparation, crystallization, and solid-state characterization of
      ethyl (3)- and butyl (4)-substituted spiro-biphenalenyl radicals. Both of these
      compounds are found to be conducting face-to-face pi-dimers in the solid state
      but with different room-temperature magnetic ground states. At room temperature,
      4 exists as a diamagnetic pi-dimer (interplanar separation of approximately 3.1
      A), whereas 3 is a paramagnetic pi-dimer (interplanar separation of approximately
      3.3 A), and both compounds show phase transitions between the paramagnetic and
      diamagnetic forms. Electrical resistivity measurements of single crystals of 3
      and 4 show that the transition from the high-temperature paramagnetic pi-dimer
      form to the low-temperature diamagnetic pi-dimer structure is accompanied by an
      increase in conductivity by about 2 orders of magnitude. This behavior is
      unprecedented and is very difficult to reconcile with the usual understanding of
      a Peierls dimerization, which inevitably leads to an insulating ground state. We
      tentatively assign the enhancement in the conductivity to a decrease in the on
      site Coulombic correlation energy (U), as the dimers form a super-molecule with
      twice the amount of conjugation.

PMID- 11457156
TI  - Probing molecular conformations with electron momentum spectroscopy: the case of
      n-butane.
AB  - High-resolution (e,2e) measurements of the valence electronic structure and
      momentum-space electron density distributions of n-butane have been exhaustively
      reanalyzed in order to cope with the presence of two stable structures in the gas
      phase, namely the all-staggered and gauche conformers. The measurements are
      compared to a series of Boltzmann-weighted simulations based on the momentum
      space form of Kohn-Sham (B3LYP) orbital densities, and to ionization spectra
      obtained from high-level [ADC(3)] one-particle Green's Function calculations.
      Indubitable improvements in the quality of the simulated (e,2e) ionization
      spectra and electron momentum profiles are seen when the contributions of the
      gauche form of n-butane are included. Both the one-electron binding energies and
      momentum distributions consistently image the distortions and topological changes
      that molecular orbitals undergo due to torsion of the carbon backbone, and
      thereby exhibit variations which can be traced experimentally. With regard to the
      intimate relation of (e,2e) cross sections with orbital densities, electron
      momentum spectroscopy can therefore be viewed as a very powerful, but up to now
      largely unexploited, conformational probe. The study also emphasizes the
      influence of thermal agitation in photoionization experiments of all kind.

PMID- 11457157
TI  - Proton-coupled electron transfer of cytochrome c.
AB  - Cytochrome c (Cyt-c) was electrostatically bound to self-assembled monolayers
      (SAM) on an Ag electrode, which are formed by omega-carboxyl alkanethiols of
      different chain lengths (C(x)). The dynamics of the electron-transfer (ET)
      reaction of the adsorbed heme protein, initiated by a rapid potential jump to the
      redox potential, was monitored by time-resolved surface enhanced resonance Raman
      (SERR) spectroscopy. Under conditions of the present experiments, only the
      reduced and oxidized forms of the native protein state contribute to the SERR
      spectra. Thus, the data obtained from the spectra were described by a one-step
      relaxation process yielding the rate constants of the ET between the adsorbed Cyt
      c and the electrode for a driving force of zero electronvolts. For C(16)- and
      C(11)-SAMs, the respective rate constants of 0.073 and 43 s(-1) correspond to an
      exponential distance dependence of the ET (beta = 1.28 A(-1)), very similar to
      that observed for long-range intramolecular ET of redox proteins. Upon further
      decreasing the chain length, the rate constant only slightly increases to 134 s(
      1) at C(6)- and remains essentially unchanged at C(3)- and C(2)-SAMs. The onset
      of the nonexponential distance dependence is paralleled by a kinetic H/D effect
      that increases from 1.2 at C(6)- to 4.0 at C(2)-coatings, indicating a coupling
      of the redox reaction with proton-transfer (PT) steps. These PT processes are
      attributed to the rearrangement of the hydrogen-bonding network of the protein
      associated with the transition between the oxidized and reduced state of Cyt-c.
      Since this unusual kinetic behavior has not been observed for electron
      transferring proteins in solution, it is concluded that at the Ag/SAM interface
      the energy barrier for the PT processes of the adsorbed Cyt-c is raised by the
      electric field. This effect increases upon reducing the distance to the
      electrode, until nuclear tunneling becomes the rate-limiting step of the redox
      process. The electric field dependence of the proton-coupled ET may represent a
      possible mechanism for controlling biological redox reactions via changes of the
      transmembrane potential.

PMID- 11457158
TI  - CASSCF and CASPT2 calculations on the cleavage and ring inversion of
      bicyclo[2.2.0]hexane find that these reactions involve formation of a common
      twist-boat diradical intermediate.
AB  - (6/6)CASSCF and CASPT2/6-31G calculations have been performed to understand the
      experimental finding of Goldstein and Benzon (J. Am. Chem. Soc. 1972, 94, 5119)
      that exo-bicyclo[2.2.0]hexane-d(4) (1b) undergoes ring inversion to form endo
      bicyclo[2.2.0]hexane-d(4) (4b) faster than it undergoes cleavage to form
      cis,trans-1,5-hexadiene-d(4) (3b). Goldstein and Benzon also found that the
      latter reaction, which must occur via a chairlike transition structure (TS), is
      much faster than cleavage of 1b to trans,trans-1,5-hexadiene-d(4) (2b) via a
      boatlike TS. Our calculations reveal that all three of these reactions involve
      ring opening of 1, through a boat diradical TS (BDTS), to form a twist-boat
      diradical intermediate (TBDI). TBDI can reclose to 4 via a stereoisomeric boat
      diradical TS (BDTS'), or TBDI can cleave, either via a half-chair diradical TS
      (HCDTS) to form 3 or via a boat TS (BTS) to form 2. The calculated values of
      DeltaH(++) = 34.6 kcal/mol, DeltaS(++) = -1.6 eu, and DeltaH(++) = 35.2 kcal/mol,
      DeltaS(++) = 2.0 eu for ring inversion of 1 to 4 and cleavage of 1 to 3,
      respectively, are in excellent agreement with the values measured by Goldstein
      and Benzon. The higher value of DeltaH(++) = 37.6 kcal/mol, computed for cleavage
      of TBDI to 2, is consistent with the experimental finding that very little 2b is
      formed when 1b is pyrolyzed. The relationships between BDTS, HCDTS, and BTS and
      the chair and boat Cope rearrangement TSs (CCTS and BCTS) are discussed.

PMID- 11457160
TI  - Facile reductive elimination of ethane from strained dimethylpalladium(II)
      complexes.

PMID- 11457159
TI  - Scanning tunneling microscopy, orbital-mediated tunneling spectroscopy, and
      ultraviolet photoelectron spectroscopy of metal(II) tetraphenylporphyrins
      deposited from vapor.
AB  - Thin films of vapor-deposited Ni(II) and Co(II) complexes of tetraphenylporphyrin
      (NiTPP and CoTPP) were studied supported on gold and embedded in Al-Al(2)O(3)
      MTPP-Pb tunnel diodes, where M = Ni or Co. Thin films deposited onto
      polycrystalline gold were analyzed by ultraviolet photoelectron spectroscopy
      (UPS) using He I radiation. Scanning tunneling microscopy (STM) and orbital
      mediated tunneling spectroscopy (STM-OMTS) were performed on submonolayer films
      of CoTPP and NiTPP supported on Au(111). Inelastic electron tunneling
      spectroscopy (IETS) and OMTS were measured in conventional tunnel diode
      structures. The highest occupied pi molecular orbital of the porphyrin ring was
      seen in both STM-OMTS and UPS at about 6.4 eV below the vacuum level. The lowest
      unoccupied pi molecular orbital of the porphyrin ring was observed by STM-OMTS
      and by IETS-OMTS to be located near 3.4 eV below the vacuum level. The OMTS
      spectra of CoTPP had a band near 5.2 eV (below the vacuum level) that was
      attributed to transient oxidation of the central Co(II) ion. That is, it is due
      to electron OMT via the half-filled d(z)(2) orbital present in Co(II) of CoTPP.
      The NiTPP OMTS spectra show no such band, consistent with the known difficulty of
      oxidation of the Ni(II) ion. The STM-based OMTS allowed these two porphyrin
      complexes to be easily distinguished. The present work is the first report of the
      observation of STM-OMTS, tunnel junction OMTS, and UPS of the same compounds.
      Scanning tunneling microscope-based orbital-mediated tunneling provides more
      information than UPS or tunnel junction-based OMTS and does so with molecular
      scale resolution.

PMID- 11457161
TI  - An efficient and convenient reaction protocol to organoimido derivatives of
      polyoxometalates.

PMID- 11457162
TI  - Peroxynitrite isomerization catalyzed by his64 myoglobin mutants.

PMID- 11457163
TI  - Fine tuning of the interaction between the copper(I) and disulfide bond.
      Formation of a bis(mu-thiolato)dicopper(II) complex by reductive cleavage of the
      disulfide bond with copper(I).

PMID- 11457164
TI  - Oxidation of self-assembled monolayers by UV light with a wavelength of 254 nm.

PMID- 11457165
TI  - Stabilization of ozone-like [Bi3](3-) in the heteroatomic closo-clusters
      [Bi3Cr2(CO)6]3- and [Bi3Mo2(CO)6](3-).

PMID- 11457166
TI  - One-pot formation of substituted cyclopentadienyl and indenyltricarbonyl rhenium
      complexes through in situ generation of cyclopentadienyl- and
      indenyltributylstannanes.

PMID- 11457167
TI  - Secondary bonding-directed self-assembly of amino acid derived benziodazoles:
      synthesis and structure of novel hypervalent iodine macrocycles.

PMID- 11457168
TI  - Stereochemical control and reactivity of Pd complexes with meso and racemic
      ligands in the isotactic alternating propene-carbon monoxide copolymerization.

PMID- 11457169
TI  - Correlations among (1)J(NC)' and (h3)J(NC)' coupling constants in the hydrogen
      bonding network of human ubiquitin.

PMID- 11457170
TI  - Selective alpha-stannylated addition of di-n-butyliodotin hydride Ate complex to
      simple aliphatic alkynes.

PMID- 11457171
TI  - Hydroxylated quantum dots as luminescent probes for in situ hybridization.

PMID- 11457172
TI  - Self-assembly of dendron rodcoil molecules into nanoribbons.

PMID- 11457173
TI  - Long-range cooperativity in molecular recognition of RNA by oligodeoxynucleotides
      with multiple C5-(1-propynyl) pyrimidines.
AB  - A heptamer composed of C5-(1-propynyl) pyrimidines (Y(p)'s) is a potent and
      specific antisense agent against the mRNA of SV40 large T antigen (Wagner, R. W.;
      Matteucci, M. D.; Grant, D.; Huang, T.; Froehler, B. C. Nat. Biotechnol. 1996,
      14, 840-844). To characterize the role of the propynyl groups in molecular
      recognition, thermodynamic increments associated with substitutions in DNA:RNA
      duplexes, such as 5'-dCCUCCUU-3':3'-rGAGGAGGAAAU-5', have been measured by UV
      melting experiments. For nucleotides tested, an unpaired dangling end stabilizes
      unmodified and propynylated duplexes similarly, except that addition of a 5'
      unpaired rA is 1.4 kcal/mol more stabilizing on the propynylated, PODN:RNA,
      duplex than on the DNA:RNA duplex. Free energy increments for addition of single
      propynyl groups range from 0 to -4.0 kcal/mol, depending on the final number and
      locations of substitutions. A preliminary model for predicting the stabilities of
      Y(p)-containing hybrid duplexes is presented. Eliminating one amino group, and
      therefore a hydrogen bond, by substituting inosine (I) for guanosine (G), to give
      5'-dC(p)C(p)U(p)C(p)C(p)U(p)U(p)-3':3'-rGAGIAGGAAAU-5', destabilizes the duplex
      by 3.9 kcal/mol, compared to 1.7 kcal/mol for the same change within the
      unpropynylated duplex. This 2.2 kcal/mol difference is eliminated by removing a
      single propynyl group three base pairs away. CD spectra suggest that single
      propynyl deletions within the PODN:RNA duplex have position-dependent effects on
      helix geometry. The results suggest long-range cooperativity between propynyl
      groups and provide insights for rationally programming oligonucleotides with
      enhanced binding and specificity. This can be exploited in developing
      technologies that are dependent upon nucleic acid-based molecular recognition.

PMID- 11457174
TI  - Asymmetric inter- and intramolecular cyclopropanation of alkenes catalyzed by
      chiral ruthenium porphyrins. Synthesis and crystal structure of a chiral
      metalloporphyrin carbene complex.
AB  - Extensive investigations of asymmetric intermolecular cyclopropanation of
      terminal alkenes with diazoacetates catalyzed by ruthenium porphyrin
      [Ru(P*)(CO)(EtOH)] (1, H2P = 5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8
      octahydro-1,4:5,8-dimethanoanthracene-9-yl]porphyrin) and the application of
      catalyst 1 to asymmetric intramolecular cyclopropanation of allylic or
      homoallylic diazoacetates are described. The intermolecular cyclopropanation of
      styrene and its derivatives with ethyl diazoacetate afforded the corresponding
      cyclopropyl esters in up to 98% ee with high trans/cis ratios of up to 36 and
      extremely high catalyst turnovers of up to 1.1 x 10(4). Examination of the
      effects of temperature, diazoacetate, solvent, and substituent in the
      intermolecular cyclopropanation reveals that (i) both enantioselectivity and
      trans selectivity increase with decreasing temperature, (ii) sterically
      encumbered diazoacetates N2CHCO2R, such as R = Bu(t), and donor solvents, such as
      diethyl ether and tetrahydrofuran, are beneficial to the trans selectivity, and
      (iii) electron-donating para substituents on styrene accelerate the
      cyclopropanations, with the log(k(X)/k(H)) vs sigma(+) plot for para-substituted
      styrenes p-X-C6H4CH=CH2 (X = MeO, Me, Cl, CF3) exhibiting good linearity with a
      small negative rho(+) value of -0.44 +/- 0.09. In the case of intramolecular
      cyclopropanation, complex 1 promoted the decomposition of a series of allylic
      diazoacetates to form the cyclopropyl lactones in up to 85% ee, contributing the
      first efficient metalloporphyrin catalyst for an asymmetric intramolecular
      cyclopropanation. Both the inter- and intramolecular cyclopropanations were
      proposed to proceed via a reactive chiral ruthenium carbene intermediate. The
      enantioselectivities in these processes were rationalized on the basis of the X
      ray crystal structures of closely related stable chiral carbene complexes
      [Ru(P*)(CPh2)] (2) and [Ru(P*)(C(Ph)CO2CH2CH=CH2)] (3) obtained from reactions of
      complex 1 with N2CPh2 and N2C(Ph)CO2CH2CH=CH2, respectively.

PMID- 11457175
TI  - Evidence of secondary structure by high-resolution magic angle spinning NMR
      spectroscopy of a bioactive peptide bound to different solid supports.
AB  - The structure of the 19-amino acid peptide epitope, corresponding to the 141-159
      sequence of capsid viral protein VP1 of foot-and-mouth disease virus (FMDV),
      bound to three different resins, namely, polystyrene-MBHA, PEGA, and POEPOP, has
      been determined by high-resolution magic angle spinning (HRMAS) NMR spectroscopy.
      A combination of homonuclear and heteronuclear bidimensional experiments was used
      for the complete peptide resonance assignment and the qualitative
      characterization of the peptide folding. The influence of the chemicophysical
      nature of the different polymers on the secondary structure of the covalently
      attached FMDV peptide was studied in detail. In the case of polystyrene-MBHA and
      polyacrylamide-PEGA resins, the analysis of the 2D spectra was hampered by
      missing signals and extensive overlaps, and only a propensity toward a peptide
      secondary structure could be derived from the assigned NOE correlations. When the
      FMDV peptide was linked to the polyoxyethylene-based POEPOP resin, it was found
      to adopt in dimethylformamide a helical conformation encompassing the C-terminal
      domain from residues 152 to 159. This conformation is very close to that of the
      free peptide previously analyzed in 2,2,2-trifluoroethanol. Our study clearly
      demonstrates that a regular helical structure can be adopted by a resin-bound
      bioactive peptide. Moreover, a change in the folding was observed when the same
      peptide-POEPOP conjugate was swollen in aqueous solution, displaying the same
      conformational features as the free peptide in water. The possibility of studying
      solid-supported ordered secondary structures by the HRMAS NMR technique in a wide
      range of solvents can be extended either to other biologically relevant peptides
      and proteins or to new synthetic oligomers.

PMID- 11457176
TI  - Formation of silazirconacyclopentenes from zirconium-silene complex and alkynes
      and their reactivities.
AB  - During the course of our study on the formation of a complex having a zirconium
      silicon bond, we found that zirconium-silene complex 7 was formed from Cp2ZrCl2
      and Me2PhSiLi. In the presence of alkyne, diarylalkyne reacted with silene
      coordinated with zirconium to give silazirconacyclopentene 8. On the other hand,
      dialkylalkyne inserted into a zirconium-silene complex gave
      silazirconacyclopentene 9. Hydrolysis of 8 or 9 afforded vinylsilane 13 or
      allylsilane 16. Transmetalation of zirconacycle 8 into copper in the presence of
      allyl halide gave a bis-allylated compound in high yield, indicating that
      alkylation occurred on the alkyne carbon and the methyl group of silicon. From
      bis-allylated compounds, eight-membered ring compounds having silicon were
      obtained in high yield using olefin metathesis.

PMID- 11457177
TI  - Mechanism and stereochemistry of diphosphate formation from dioxaphosphorinanes:
      a critical reassessment.
AB  - The mechanism of diphosphate formation from (R)-2-chloro-2-oxo-5,5-dimethyl-4-(R)
      phenyl-1,3,2-dioxaphosphorinane (5a) and 2-hydroxy-2-oxo-5,5-dimethyl-4-(R)
      phenyl-1,3,2-dioxaphosphorinane (6) has been investigated. The products formed
      are the ax-ax diphosphate 7a and the ax-eq diphosphate 7b, with no evidence in
      the 31P NMR spectrum for pentacoordinate chlorooxyanionic phosphoranes 9. The
      structure of 7bhas been established unambiguously by NMR spectroscopy, mass
      spectrometry, and elemental analysis, and the structures of 5a and 7a have been
      confirmed by X-ray crystallography. The mechanism of the crucial diphosphate
      forming reaction has been probed using 18O-labeling studies. The 18O-labeling
      patterns are consistent with the unsymmetric ax-eq diphosphate 7b arising from
      selective nucleophilic attack of the axial oxygen of 6 on the chloride 5a with
      inversion of configuration at phosphorus. The symmetric ax-ax diphosphate 7a can
      be formed directly, as a result of selective nucleophilic attack of the axial
      oxygen of 6 on the chloride 5a with retention of configuration, but the majority
      arises indirectly by isomerization of the ax-eq diphosphate 7b. The isomerization
      apparently involves intermolecular exchange, with nucleophilic attack of the
      phosphate anion 6 on the equatorially substituted phosphorus atom of 7b with
      inversion of configuration at phosphorus.

PMID- 11457178
TI  - Atom-efficient metal-catalyzed cross-coupling reaction of indium organometallics
      with organic electrophiles.
AB  - The novel metal-catalyzed cross-coupling reaction of indium organometallics with
      organic electrophiles is described. Triorganoindium compounds (R(3)In) containing
      alkyl, vinyl, aryl, and alkynyl groups are efficiently prepared from the
      corresponding lithium or magnesium organometallics by reaction with indium
      trichloride. The cross-coupling reaction of R(3)In with aryl halides and
      pseudohalides (iodide 2, bromide 5, and triflate 4), vinyl triflates, benzyl
      bromides, and acid chlorides proceeds under palladium catalysis in excellent
      yields and with high chemoselectivity. Indium organometallics also react with
      aryl chlorides as under nickel catalysis. In the cross-coupling reaction the
      triorganoindium compounds transfer, in a clear example of atom economy, all three
      of the organic groups attached to the metal, as shown by the necessity of using
      only 34 mol % of indium. The feasibility of using R(3)In in reactions with
      different electrophiles, along with the high yields and chemoselectivities
      obtained, reveals indium organometallics to be useful alternatives to other
      organometallics in cross-coupling reactions.

PMID- 11457179
TI  - Total synthesis of fostriecin (CI-920).
AB  - The first total synthesis of the potent antitumor agent fostriecin (CI-920) is
      described, confirming the relative and absolute stereochemistry assignments.
      Fostriecin is a unique phosphate monoester which exhibits weak topoisomerase II
      inhibition (IC(50) = 40 microM) and more potent and selective protein phosphatase
      2A and 4 (PP2A and PP4) inhibition (IC(50) = 40-3 nM and 1.5 nM), resulting in
      mitotic entry checkpoint inhibition. Phase I clinical trials with fostriecin,
      which were the first to explore the potential of this novel mechanism of action,
      were halted even before therapeutic concentrations were reached or dose-limiting
      toxicity established due to problems of drug stability observed during storage of
      naturally derived material. The synthesis of fostriecin detailed herein is the
      first stage of efforts that may serve to address these limitations to the
      clinical examination of this or related promising new antitumor agents.

PMID- 11457180
TI  - Structure, properties, and bonding of ZrTe (MnP type), a low-symmetry, high
      temperature modification of ZrTe (WC type).
AB  - ZrTe (MnP) was synthesized by high-temperature methods at 1570 K in Ta ampules.
      The structure of the telluride was determined by means of single-crystal X-ray
      diffraction to be orthorhombic, Pnma (No. 62), Z = 4, Pearson Symbol oP8, a =
      739.15(15) pm, b = 377.23(8) pm, c = 694.34(14) pm. The orthorhombic MnP type
      structure is a distorted variant of the NiAs type structure with pronounced metal
      metal zigzag chains. Zigzag chains are typical for phases with a d(2) metal atom
      electron configuration. According to extended Huckel calculations, the
      homonuclear interactions in the zigzag chains make up for 2/3 of the Zr-Zr
      interactions in ZrTe (MnP) and contribute decisively to the stability of the
      structure. The emergence of the distorted MnP type structure instead of the high
      symmetry NiAs type ZrTe at high temperatures can be understood as the result of
      an optimization of homonuclear Zr-Zr interactions arising from states close to
      the Fermi level. The hexagonal WC type ZrTe transforms above 1438 +/- 5 K into
      ZrTe (MnP) (DeltaH = 8.3 +/- 1.0 kJ mol(-1)). The phase transition is reversible,
      although at room-temperature the reverse reaction is kinetically inhibited.
      Zr5Te4 and Zr5Te6 are the phases next to ZrTe. ZrTe (MnP) exhibits temperature
      independent paramagnetic properties (chi(mol) = 0.14 x 10(-3) cm(3) mol(-1)), as
      typical for a metallic conductor. Resistivity measurements on ZrTe (MnP) imply
      metallic behavior.

PMID- 11457181
TI  - New organic superconductors beta-(BDA-TTP)2X [BDA-TTP + 2,5-bis(1,3-dithian
      2ylidene)-1,3,4,6-tetrathiapentalene; X(-) = SbF6(-), AsF6(-), and PF6(-)].
AB  - The synthesis, electrochemical properties, and molecular structure of a new pi
      electron donor, 2,5-bis(1,3-dithian-2-ylidene)-1,3,4,6-tetrathiapentalene (BDA
      TTP), is described. In contrast to the hitherto-known tetrachalcogenafulvalene pi
      donors providing organic superconductors, this donor contains only the bis-fused
      1,3-dithiole-2-ylidene unit as a pi-electron system, yet produces a series of
      ambient-pressure superconductors beta-(BDA-TTP)2X [X = SbF6 (magnetic T(c) = 6.9
      K, resistive T(c) = 7.5 K), AsF6 (magnetic T(c) = 5.9 K, resistive T(c) = 5.8 K),
      and PF6 (magnetic T(c) = 5.9 K)], which are isostructural. The values of the
      intermolecular overlap integrals calculated on the donor layers of these
      superconductors suggest a two-dimensional (2D) electronic structure with loose
      donor packing. Tight-binding band calculations also indicate that these
      superconductors have the 2D band dispersion relations and closed Fermi surfaces.

PMID- 11457182
TI  - Magnetic susceptibility tensor anisotropies for a lanthanide ion series in a
      fixed protein matrix.
AB  - The full series of lanthanide ions (except the radioactive promethium and the S
      state gadolinium) has been incorporated into the C-terminal calcium binding site
      of the dicalcium protein calbindin D(9k). A fairly constant coordination
      environment is maintained throughout the series. At variance with several
      lanthanide complexes with small chelating ligands investigated in the past, the
      large protein moiety provides a large number of NMR signals whose hyperfine
      shifts can be exclusively ascribed to pseudocontact shifts (PCS). The chemical
      shifts of 1H and 15N backbone and side chain amide NH groups were accurately
      measured through HSQC experiments. 1097 PCS were estimated from these by
      subtracting the diamagnetic contributions measured on HSQC spectra of either the
      4f(0) lanthanum(III) or the 4f(14) lutetium(III) derivatives and used to define a
      quality factor for the structure. The differences in diamagnetic chemical shifts
      between the two diamagnetic blanks were relatively small, although some were not
      negligible especially for the nuclei closest to the metal center. These
      differences were used as a tolerance for the PCS. The magnetic susceptibility
      tensor anisotropies for each paramagnetic lanthanide ion were obtained as the
      result of the solution structure determination performed by using the NOEs of the
      cerium(III) derivative and the PCS of all lanthanides simultaneously. This set of
      reliable magnetic data permits an experimental assessment of Bleaney's theory
      relative to the magnetic properties for an extended series of lanthanide
      complexes in solution. All of the obtained tensors show some rhombicity, as could
      be expected from the lack of symmetry of the protein environment. The directions
      of the largest magnetic susceptibility component for Ce, Pr, Nd, Sm, Tb, Dy, and
      Ho and of the smallest magnetic susceptibility component for Eu, Er, Tm, and Yb
      were found to be all within 15 degrees from their average (within 20 degrees for
      Sm), confirming the essential similarity of the coordination environment for all
      lanthanides. Bleaney's theory is in excellent qualitative agreement with the
      observed pattern of axial anisotropies. Its quantitative agreement is
      substantially better than that suggested by previous analyses performed on more
      limited sets of PCS data for small lanthanide complexes, the so-called crystal
      field parameter varying only within +/-30% from one lanthanide to another. These
      variations are even smaller (+/-15%) if a reasonable T(-3) correction is taken
      into consideration. A knowledge of magnetic susceptibility anisotropy properties
      of lanthanides is essential in determining the self-orienting properties of
      lanthanide complexes in solution when immersed in magnetic fields.

PMID- 11457183
TI  - The electron as a protecting group. 3. Generation of acenaphthyne radical anion
      and the determination of the heat of formation of a strained cycloalkyne.
AB  - Acenaphthyne dicarboxylate (12) was transferred into the gas phase from solution
      via electrospray ionization and subsequently was sequentially fragmented in a
      Fourier transform mass spectrometer to afford acenaphthyne radical anion (9).
      Structural confirmation of 9 was achieved by converting it to acenaphthenone
      enolate (13) and demonstrating that this species is identical to the ion produced
      upon deprotonation of acenaphthenone (5). The reactivity of 9 was explored, and
      since an electron can serve as a protecting group, we were able to measure the
      heat of hydrogenation (98 +/- 4 kcal mol(-1)) and the heat of formation (160 +/-
      4 kcal mol(-1)) of acenaphthyne (1) via the application of a thermodynamic cycle.
      Its strain energy (68 kcal mol(-1)) and acenaphthylene's (10H) first and second C
      H bond dissociation energies (117 +/- 4 and 84 +/- 2 kcal mol(-1)) also were
      obtained. Ab initio and density functional theory calculations were carried out
      on the species of interest to explore their geometries and energetics. Our
      results were interpreted in comparison to cyclopentyne, and its predicted heat of
      formation (98 kcal mol(-1)) and strain energy (59 kcal mol(-1)) are reported.

PMID- 11457184
TI  - Isodiiodomethane is the methylene transfer agent in cyclopropanation reactions
      with olefins using ultraviolet photolysis of diiodomethane in solutions: a
      density functional theory investigation of the reactions of isodiiodomethane,
      iodomethyl radical, and iodomethyl cation with ethylene.
AB  - We examine the chemical reactions of the isodiiodomethane (CH2I-I), .CH2I and
      CH2I(+) species with ethylene using density functional theory computations. The
      CH2I-I species readily reacts with ethylene to give the cyclopropane product and
      an I2 product via a one-step reaction with a barrier height of approximately 2.9
      kcal/mol. However, the.CH2I and CH2I(+) species have much more difficult pathways
      (with larger potential barriers) to react with ethylene via a two-step reaction
      mechanism. Comparison of experimental results to our present calculation results
      indicates that the CH2I-I photoproduct species is most likely the methylene
      transfer agent for the cyclopropanation reaction of olefins via ultraviolet
      photoexcitation of diiodomethane.

PMID- 11457185
TI  - Femtosecond infrared study of the dynamics of solvation and solvent caging.
AB  - The ultrafast reaction dynamics following 295-nm photodissociation of Re2CO10
      were studied experimentally with 300-fs time resolution in the reactive, strongly
      coordinating CCl4 solution and in the inert, weakly coordinating hexane solution.
      Density-functional theoretical (DFT) and ab initio calculations were used to
      further characterize the transient intermediates seen in the experiments. It was
      found that the quantum yield of the Re-Re bond dissociation is governed by
      geminate recombination on two time scales in CCl4, approximately 50 and
      approximately 500 ps. The recombination dynamics are discussed in terms of
      solvent caging in which the geminate Re(CO)5 pair has a low probability to escape
      the first solvent shell in the first few picoseconds after femtosecond
      photolysis. The other photofragmentation channel resulted in the equatorially
      solvated dirhenium nonacarbonyl eq-Re2(CO)9(solvent). Theoretical calculations
      indicated that a structural reorganization energy cost on the order of 6-7
      kcal/mol might be required for the unsolvated nonacarbonyl to coordinate to a
      solvent molecule. These results suggest that for Re(CO)5 the solvent can be
      treated as a viscous continuum, whereas for the Re2(CO)9 the solvent is best
      described in molecular terms.

PMID- 11457186
TI  - Structure of the P700(+ )A1(-) radical pair intermediate in photosystem I by high
      time resolution multifrequency electron paramagnetic resonance: analysis of
      quantum beat oscillations.
AB  - The geometry of the secondary radical pair P700(+)A1(-), in photosystem I (PSI)
      from the deuterated and 15N-substituted cyanobacterium Synechococcus lividus, has
      been determined by high time resolution electron paramagnetic resonance (EPR),
      performed at three different microwave frequencies. Structural information is
      extracted from light-induced quantum beats observed in the transverse
      magnetization of P700(+)A1(-) at early times after laser excitation. A computer
      analysis of the two-dimensional Q-band experiment provides the orientation of the
      various magnetic tensors of with respect to a magnetic reference frame. The
      orientation of the cofactors of the primary donor in the g-tensor system of is
      then evaluated by analyzing time-dependent X-band EPR spectra, extracted from a
      two-dimensional data set. Finally, the cofactor arrangement of P700(+)A1(-) in
      the photosynthetic membrane is deduced from angular-dependent W-band spectra,
      observed for a magnetically aligned sample. Thus, the orientation of the g-tensor
      of P700(+) with respect to a chlorophyll based reference system could be
      determined. The angle between the g1(z) axis and the chlorophyll plane normal is
      found to be 29 +/- 7 degrees, while the g1(y) axis lies in the chlorophyll plane.
      In addition, a complete structural model for the reduced quinone acceptor, A1(-),
      is evaluated. In this model, the quinone plane of is found to be inclined by 68
      +/- 7 degrees relative to the membrane plane, while the P700(+)-A1(-) axis makes
      an angle of 35 +/- 6 degrees with the membrane normal. All of these values refer
      to the charge separated state, observed at low temperatures, where forward
      electron transfer to the iron-sulfur centers is partially blocked. Preliminary
      room temperature studies of P700(+)A1(-), employing X-band quantum beat
      oscillations, indicate a different orientation of A1(-) in its binding pocket. A
      comparison with crystallographic data provides information on the electron
      transfer pathway in PSI. It appears that quantum beats represent excellent
      structural probes for the short-lived intermediates in the primary energy
      conversion steps of photosynthesis.

PMID- 11457187
TI  - Comparisons in the behavior of stable copper(II), silver(II), and gold(II)
      complexes in the gas phase: are there implications for condensed-phase chemistry?
AB  - Experiments conducted in the gas phase have led to the formation of a series of
      stable gold(II) complexes with nitrogen- and oxygen-containing ligands. Such
      complexes are very rare in condensed-phase chemistry. However, there is also a
      significant group of potential ligands, for example, H2O and NH3, for which
      stable complexes could not be formed. There are strong similarities between these
      observations and earlier results presented for silver(II), but both metal ions
      behave markedly different from copper(II). As a group the majority of successful
      gold(II) ligands are characterized by being good sigma donor-pi acceptor
      molecules; however, it is also possible to understand the ability of individual
      ligands to stabilize the metal ion in terms of a simple electrostatic model.
      Application of the latter reveals a semiquantitative trend between the physical
      properties of a ligand, e.g. ionization energy, dipole moment, and
      polarizability, and the ligand's ability to stabilize either Cu(II), Ag(II), or
      Au(II). The model successfully accounts for the preference of Cu(II) for aqueous
      chemistry, in comparison to the complete absence of such behavior on the part of
      Ag(II) and Au(II). Ligands from recent examples of stable condensed-phase
      gold(II) complexes appear to meet at least one of the criteria identified from
      the model.

PMID- 11457188
TI  - Reactions of the alkoxy radicals formed following OH-addition to alpha-pinene and
      beta-pinene. C-C bond scission reactions.
AB  - The atmospheric degradation pathways of the atmospherically important terpenes
      alpha-pinene and beta-pinene are studied using density functional theory. We
      employ the correlation functional of Lee, Yang, and Parr and the three-parameter
      HF exchange functional of Becke (B3LYP) together with the 6-31G(d) basis set. The
      C-C bond scission reactions of the beta-hydroxyalkoxy radicals that are formed
      after OH addition to alpha-pinene and beta-pinene are investigated. Both of the
      alkoxy radicals formed from the alpha-pinene-OH adduct possess a single favored C
      C scission pathway with an extremely low barrier (approximately 3 kcal/mol)
      leading to the formation of pinonaldehyde. Neither of these pathways produces
      formaldehyde, and preliminary computational results offer some support for
      suggestions that 1,5 or 1,6 H-shift (isomerization) reactions of alkoxy radicals
      contribute to formaldehyde production. In the case of the alkoxy radical formed
      following OH addition to the methylene group of beta-pinene, there exists two C-C
      scission reactions with nearly identical barrier heights (approximately 7.5
      kcal/mol); one leads to known products (nopinone and formaldehyde) but the
      ultimate products of the competing reaction are unknown. The single C-C scission
      pathway of the other alkoxy radical from beta-pinene possesses a very low
      (approximately 4 kcal/mol) barrier. The kinetically favored C-C scission
      reactions of all four alkoxy radicals appear to be far faster than expected rates
      of reaction with O2. The rearrangement of the alpha-pinene-OH adduct, a key step
      in the proposed mechanism of formation of acetone from alpha-pinene, is
      determined to possess a barrier of 11.6 kcal/mol. This value is consistent with
      another computational result and is broadly consistent with the modest acetone
      yields observed in product yield studies.

PMID- 11457189
TI  - Catalytic water formation on platinum: a first-principles study.
AB  - The study of catalytic behavior begins with one seemingly simple process, namely
      the hydrogenation of O to H2O on platinum. Despite the apparent simplicity its
      mechanism has been much debated. We have used density functional theory with
      gradient corrections to examine microscopic reaction pathways for several
      elementary steps implicated in this fundamental catalytic process. We find that
      H2O formation from chemisorbed O and H atoms is a highly activated process. The
      largest barrier along this route, with a value of approximately 1 eV, is the
      addition of the first H to O to produce OH. Once formed, however, OH groups are
      easily hydrogenated to H2O with a barrier of approximately 0.2 eV.
      Disproportionation reactions with 1:1 and 2:1 stoichiometries of H2O and O have
      been examined as alternative routes for OH formation. Both stoichiometries of
      reaction produce OH groups with barriers that are much lower than that associated
      with the O + H reaction. H2O, therefore, acts as an autocatalyst in the overall
      H2O formation process. Disproportionation with a 2:1 stoichiometry is
      thermodynamically and kinetically favored over disproportionation with a 1:1
      stoichiometry. This highlights an additional (promotional) role of the second H2O
      molecule in this process. In support of our previous suggestion that the key
      intermediate in the low-temperature H2O formation reaction is a mixed OH and H2O
      overlayer we find that there is a very large barrier for the dissociation of the
      second H2O molecule in the 2:1 disproportionation process. We suggest that the
      proposed intermediate is then hydrogenated to H2O through a very facile proton
      transfer mechanism.

PMID- 11457190
TI  - Solution 1H NMR of the molecular and electronic structure of the heme cavity and
      substrate binding pocket of high-spin ferric horseradish peroxidase: effect of
      His42Ala mutation.
AB  - Solution 1H NMR has been used to assign a major portion of the heme environment
      and the substrate-binding pocket of resting state horseradish peroxidase, HRP,
      despite the high-spin iron(III) paramagnetism, and a quantitative interpretive
      basis of the hyperfine shifts is established. The effective assignment protocol
      included 2D NMR over a wide range of temperatures to locate residues shifted by
      paramagnetism, relaxation analysis, and use of dipolar shifts predicted from the
      crystal structure by an axial paramagnetic susceptibility tensor normal to the
      heme. The most effective use of the dipolar shifts, however, is in the form of
      their temperature gradients, rather than by their direct estimation as the
      difference of observed and diamagnetic shifts. The extensive assignments allowed
      the quantitative determination of the axial magnetic anisotropy, Deltachi(ax) = 
      2.50 x 10(-8) m(3)/mol, oriented essentially normal to the heme. The value of
      Deltachi(ax) together with the confirmed T(-2) dependence allow an estimate of
      the zero-field splitting constant D = 15.3 cm(-1), which is consistent with
      pentacoordination of HRP. The solution structure was generally indistinguishable
      from that in the crystal (Gajhede, M.; Schuller, D. J.; Henriksen, A.; Smith, A.
      T.; Poulos, T. L. Nature Structural Biology 1997, 4, 1032-1038) except for Phe68
      of the substrate-binding pocket, which was found turned into the pocket as found
      in the crystal only upon substrate binding (Henriksen, A.; Schuller, D. J.; Meno,
      K.; Welinder, K. G.; Smith, A. T.; Gajhede, M. Biochemistry 1998, 37, 8054-8060).
      The reorientation of several rings in the aromatic cluster adjacent to the
      proximal His170 is found to be slow on the NMR time scale, confirming a dense,
      closely packed, and dynamically stable proximal side up to 55 degrees C. Similar
      assignments on the H42A-HRP mutant reveal conserved orientations for the majority
      of residues, and only a very small decrease in Deltachi(ax) or D, which dictates
      that five-coordination is retained in the mutant. The two residues adjacent to
      residue 42, Ile53 and Leu138, reorient slightly in the mutant H42A protein. It is
      concluded that effective and very informative 1H NMR studies of the effect of
      either substrate binding or mutation can be carried out on resting state heme
      peroxidases.

PMID- 11457191
TI  - Cooperative enhancement of water binding to crownophane by multiple hydrogen
      bonds: analysis by high level ab initio calculations.
AB  - The intermolecular interaction energy of the model system of the water
      crownophane complex was analyzed. The water molecule has four hydrogen bonds,
      with the two hydrogen-donating phenolic hydroxy groups and two hydrogen-accepting
      oxygen atoms of the poly-oxyethylene chain of the crownophane in the complex. The
      MP2/6-311G(2d,2p) level calculations of the model system of the complex (hydrogen
      donating unit + hydrogen accepting unit + water) indicate that the binding energy
      of the water is 21.85 kcal/mol and that the hydrogen bond cooperativity increases
      the binding energy as much as 3.67 kcal/mol. The calculated interaction energies
      depend on the basis set, while the basis set dependence of the cooperative
      increment is negligible. Most of the cooperative increment is covered by the HF
      level calculation, which suggests that the major source of the hydrogen bond
      cooperativity in this system has its origin in induction. The BLYP/6-311G** and
      PW91/6-311G** level interaction energies of the model system are close to the
      MP2/6-311G** interaction energies, which suggests that the DFT calculations with
      these functionals are useful methods to evaluated the interactions of hydrogen
      bonded systems.

PMID- 11457192
TI  - Steps to demarcate the effects of chromophore aggregation and planarization in
      poly(phenyleneethynylene)s. 1. Rotationally interrupted conjugation in the
      excited states of 1,4-bis(phenylethynyl)benzene.
AB  - A series of photophysical measurements and semiempirical calculations were
      carried out with 1,4-bis(phenylethynyl)benzene in search of evidence on the
      effects of phenyl group rotation and chromophore aggregation of oligo- and
      poly(phenyleneethynylene)s. It is suggested that planarization gives rise to
      relatively modest shifts of ca. 20-30 nm, which preserve the vibronic structure
      of the monomer and retain a high emission quantum yield. In contrast, it is
      proposed that aggregation gives rise to larger shifts and loss of vibronic
      structure.

PMID- 11457193
TI  - Solution 1H NMR characterization of axial interactions of the proximal and distal
      His in the cyanomet complexes of the isolated chains and the 65 kDa intact
      tetramer of human hemoglobin A.
AB  - Solution 1H NMR has been used to investigate the axial bonding of the proximal
      His and the hydrogen-bonding of the distal His to the bound ligand in the
      isolated chains as well as the subunits of intact, tetrameric, cyanomet human
      hemoglobin A. The complete proximal His, including all ring protons necessary to
      monitor bonding in each subunit, could be definitively assigned by 1D/2D methods
      despite the large size (approximately 65 kDa) and severe relaxation (to T(1)
      approximately 3 ms, line width approximately 1.5 kHz) of two of the protons. The
      complete distal His E7 ring was assigned in the alpha-chain and alpha-subunit of
      HbA, and the dipolar shifts and relaxation were analyzed to reveal a disposition
      intermediate between the positions adopted in HbCO and HbO2 that is optimal for
      forming a hydrogen bond with bound cyanide. The lability of the alpha-subunit His
      E7 NepsilonH is found to be similar to that in sperm whale cyanomet myoglobin.
      The orientation of the distal His E7 in the beta-subunit is found to be
      consistent with that seen in either HbCO or HbO2. While the His E7 labile
      NepsilonH proton signal could not be detected in either the beta-chain or
      subunit, it is concluded that this more likely reflects increased lability over
      that of the alpha-subunit, and not the absence of a hydrogen bond to the bound
      ligand. Analysis of the heme mean methyl hyperfine shift, which has been shown to
      be very sensitive to the presence of distal hydrogen bonds to bound cyanide
      (Nguyen, B. D.; Xia, Z.; Cutruzzola, F.; Travaglini Allocatelli, C.; Brancaccio,
      A.; Brunori, M.; La Mar, G. N. J. Biol. Chem. 2000, 275, 742-751), directly
      supports the presence of a distal His E7 hydrogen bond to cyanide in the beta
      chain and beta-subunit which is weaker than the same hydrogen bond in the alpha
      subunit. The potential for the proximal His hyperfine shifts in serving as
      indicators of axial strain in the allosteric transition of HbA is discussed.

PMID- 11457194
TI  - An investigation of the hydrogen-bonding structure in bilirubin by 1H double
      quantum magic-angle spinning solid-state NMR spectroscopy.
AB  - The complex hydrogen-bonding arrangement in the biologically important molecule
      bilirubin IXalpha is probed by using 1H double-quantum (DQ) magic-angle spinning
      (MAS) NMR spectroscopy. Employing fast MAS (30 kHz) and a high magnetic field
      (16.4 T), three low-field resonances corresponding to the different hydrogen
      bonding protons are resolved in a 1H MAS NMR spectrum of bilirubin. These
      resonances are assigned on the basis of the proton-proton proximities identified
      from a two-dimensional rotor-synchronized 1H DQ MAS NMR spectrum. An analysis of
      1H DQ MAS spinning-sideband patterns for the NH protons in bilirubin allows the
      quantitative determination of proton-proton distances and the geometry. The
      validity of this procedure is proven by simulated spectra for a model three-spin
      system, which show that the shortest distance can be determined to a very high
      degree of accuracy. The distance between the lactam and pyrrole NH protons in
      bilirubin is determined to be 0.186 +/- 0.002 nm (corresponding to a dominant
      dipolar coupling constant of 18.5 +/- 0.5 kHz). The analysis also yields a
      distance between the lactam NH and carboxylic acid OH protons of 0.230 +/- 0.008
      nm (corresponding to a perturbing dipolar coupling constant of 9.9 +/- 1.0 kHz)
      and an H-H-H angle of 122 +/- 4 degrees. Finally, a comparison of 1H DQ MAS
      spinning-sideband patterns for bilirubin and its dimethyl ester reveals a
      significantly longer distance between the two NH protons in the latter case.

PMID- 11457195
TI  - Dynamics of structure and energy of horse carboxymyoglobin after
      photodissociation of carbon monoxide.
AB  - The energetics and structural volume changes after photodissociation of
      carboxymyoglobin are quantitatively investigated by laser-induced transient
      grating (TG) and photoacoustic calorimetric techniques. Various origins of the TG
      signal are distinguished: the phase grating signals due to temperature change,
      due to absorption spectrum change, and due to volume change. We found a new
      kinetics of approximately 700 ns (at room temperature), which was not observed by
      the flash photolysis technique. This kinetics should be attributed to the
      intermediate between the geminate pair and the fully dissociated state. The
      enthalpy of an intermediate species is determined to be 61 +/- 10 kJ/mol, which
      is smaller than the expected Fe-CO bond energy. The volume of MbCO slightly
      contracts (5 +/- 3 cm(3)/mol) during this process. CO is fully released from the
      protein by an exponential kinetics from 25 to -2 degrees C. During this escaping
      process, the volume expands by 14.7 +/- 2 cm(3)/mol at room temperature and 14 +/
      10 kJ/mol is released, which should represent the protein relaxation and the
      solvation of the CO (the enthalpy of this final state is 47 +/- 10 kJ/mol). A
      potential barrier between the intermediate and the fully dissociated state is
      DeltaH(*) = 41.3 kJ/mol and DeltaS(*) = 13.6 J mol(-1) K(-1). The TG experiment
      under a high wavenumber reveals that the volume expansion depends on the
      temperature from 25 to -2 degrees C. The volume changes and the energies of the
      intermediate species are discussed.

PMID- 11457196
TI  - Monitoring the conformational fluctuations of DNA hairpins using single-pair
      fluorescence resonance energy transfer.
AB  - We present single-pair fluorescence resonance energy transfer (spFRET)
      observations of individual opening and closing events of surface-immobilized DNA
      hairpins. Two glass-surface immobilization strategies employing the biotin
      streptavidin interaction and a third covalent immobilization strategy involving
      formation of a disulfide bond to a thiol-derivatized glass surface are described
      and evaluated. Results from image and time-trace data from surface-immobilized
      molecules are compared with those from freely diffusing molecules, which are
      unperturbed by surface interactions. Using a simple two-state model to analyze
      the open and closed time distributions for immobilized hairpins, we calculate the
      lifetimes of the two states. For hairpins with a loop size of 40 adenosines and a
      stem size of either seven or nine bases, the respective closed-state lifetimes
      are 45 +/- 2.4 and 103 +/- 6.0 ms, while the respective open-state lifetimes are
      133 +/- 5.5 and 142 +/- 22 ms. These results show that the open state of the
      hairpin is favored over the closed state of the hairpin under these conditions,
      consistent with previous diffusion fluorescence correlation spectroscopy (FCS)
      experiments on poly(A)-loop hairpins. The measured open-state lifetime is about
      30 times longer than the calculated 3 ms open-state lifetime for both hairpins
      based on a closing rate scaling factor derived from a previous FCS study for
      hairpins in diffusion with 12-30 thymidines in their loops. As predicted, the
      closed-state lifetime is dependent on the stem length and is independent of the
      loop characteristics. Our findings indicate that current models should consider
      sequence dependence in calculating ssDNA thermostability. The surface
      immobilization chemistries and other experimental techniques described here
      should prove useful for studies of single-molecule populations and dynamics.

PMID- 11457197
TI  - Highly phosphorescent bis-cyclometalated iridium complexes: synthesis,
      photophysical characterization, and use in organic light emitting diodes.
AB  - The synthesis and photophysical study of a family of cyclometalated iridium(III)
      complexes are reported. The iridium complexes have two cyclometalated (C(**)N)
      ligands and a single monoanionic, bidentate ancillary ligand (LX), i.e.,
      C(**)N2Ir(LX). The C(**)N ligands can be any of a wide variety of organometallic
      ligands. The LX ligands used for this study were all beta-diketonates, with the
      major emphasis placed on acetylacetonate (acac) complexes. The majority of the
      C(**)N2Ir(acac) complexes phosphoresce with high quantum efficiencies (solution
      quantum yields, 0.1-0.6), and microsecond lifetimes (e.g., 1-14 micros). The
      strongly allowed phosphorescence in these complexes is the result of significant
      spin-orbit coupling of the Ir center. The lowest energy (emissive) excited state
      in these C(**)N2Ir(acac) complexes is a mixture of (3)MLCT and (3)(pi-pi) states.
      By choosing the appropriate C(**)N ligand, C(**)N2Ir(acac) complexes can be
      prepared which emit in any color from green to red. Simple, systematic changes in
      the C(**)N ligands, which lead to bathochromic shifts of the free ligands, lead
      to similar bathochromic shifts in the Ir complexes of the same ligands,
      consistent with "C(**)N2Ir"-centered emission. Three of the C(**)N2Ir(acac)
      complexes were used as dopants for organic light emitting diodes (OLEDs). The
      three Ir complexes, i.e., bis(2-phenylpyridinato-N,C2')iridium(acetylacetonate)
      [ppy2Ir(acac)], bis(2-phenyl benzothiozolato-N,C2')iridium(acetylacetonate)
      [bt2Ir(acac)], and bis(2-(2'-benzothienyl)pyridinato
      N,C3')iridium(acetylacetonate) [btp2Ir(acac)], were doped into the emissive
      region of multilayer, vapor-deposited OLEDs. The ppy2Ir(acac)-, bt2Ir(acac)-, and
      btp2Ir(acac)-based OLEDs give green, yellow, and red electroluminescence,
      respectively, with very similar current-voltage characteristics. The OLEDs give
      high external quantum efficiencies, ranging from 6 to 12.3%, with the
      ppy2Ir(acac) giving the highest efficiency (12.3%, 38 lm/W, >50 Cd/A). The
      btp2Ir(acac)-based device gives saturated red emission with a quantum efficiency
      of 6.5% and a luminance efficiency of 2.2 lm/W. These C(**)N2Ir(acac)-doped OLEDs
      show some of the highest efficiencies reported for organic light emitting diodes.
      The high efficiencies result from efficient trapping and radiative relaxation of
      the singlet and triplet excitons formed in the electroluminescent process.

PMID- 11457198
TI  - A unifying electron-counting rule for macropolyhedral boranes, metallaboranes,
      and metallocenes.
AB  - A generally applicable electron-counting rule-the mno rule-that integrates
      macropolyhedral boranes, metallaboranes, and metallocenes and any combination
      thereof is presented. According to this rule, m + n + o number of electron pairs
      are necessary for a macropolyhedral system to be stable. Here, m is the number of
      polyhedra, n is the number of vertices, and o is the number of single-vertex
      sharing condensations. For nido and arachno arrangements, one and two additional
      pairs of electrons are required. Wade's n + 1 rule is a special case of the mno
      rule, where m = 1 and o = 0. B20H16, for example has m = 2 and n = 20, leading to
      22 electron pairs. Ferrocene, with two nido polyhedral fragments, has m = 2, n =
      11, and o = 1, making the total 2 + 11 + 1 + 2 = 16. The generality of the mno
      rule is demonstrated by applying it to a variety of known macropolyhedral boranes
      and heteroboranes. We also enumerate the various pathways for condensation by
      taking icosahedral B12 as the model. The origin of the mno rule is explored by
      using fragment molecular orbitals. This clearly shows that the number of skeletal
      bonding molecular orbitals of two polyhedral fragments remains unaltered during
      exohedral interactions. This is true even when a single vertex is shared,
      provided the common vertex is large enough to avoid nonbonding interactions of
      adjacent vertices on either side. But the presence of more than one common vertex
      results in the sharing of surface orbitals thereby, reducing the electronic
      requirements.

PMID- 11457199
TI  - Polyhedral boranes and elemental boron: direct structural relations and diverse
      electronic requirements.
AB  - Details of the electronic and structural connections between macropolyhedral
      boranes and elemental boron are reported. The nature of electron deficiency in
      the beta-rhombohedral polymorph of boron is analyzed by using a molecular
      fragments approach with boranes as model systems. The B57H36 molecule constructed
      from such an approach has three more electrons than mandated by the electron
      counting rules (Balakrishnarajan, M. M.; Jemmis, E. D. J. Am. Chem. Soc. 2000,
      122, 456. Jemmis, E. D.; Balakrishnarajan, M. M.; Pancharatna, P. D. J. Am Chem.
      Soc. 2001, 123, 4313-4323.) devised for macropolyhedral boranes. This is also
      confirmed by electronic structure calculations at the extended Huckel and B3LYP/6
      31G levels. The aromaticity of this B57H36(3+) molecule is on par with the most
      stable B12H12(2-) itself, as revealed by nuclear independent chemical shift
      calculations. The B57 skeleton can be made electron precise by adopting a nido
      arrangement by eliminating an atom from the closo skeleton, so that three valence
      electrons will be removed. The exact site of elimination, governed by
      thermodynamic factors, necessitates the removal of a boron atom from any of the
      six symmetrically equivalent B[13] sites in the unit cell. This leads to partial
      occupancies, which causes disorder in packing, as revealed by X-ray structure
      studies. The rest of the boron atoms are distributed in icosahedral B12
      fragments, whose two-electron deficiency is satisfied by the capping of extra
      atoms, distributed statistically in the interstitial sites. These results show
      that the three-dimensional network of the idealized beta-rhombohedral unit cell
      is not stable, unlike the electron-precise carbon polymorphs such as diamond and
      graphite. Thus, disorder in the form of partial occupancies, interstitial atoms,
      alien atoms, etc., is necessary for electron sufficiency and hence for the
      stability of this polymorphic form. Through these ingenious steps, all components
      of the unit cell attain electron sufficiency, which explains the high
      thermodynamic stability of the polymorph. The connection established between
      boranes and elemental boron in terms of their structure and distribution of
      electrons has important implications in understanding the structure of boron-rich
      solids and new strategies to utilize their diverse and technologically important
      properties.

PMID- 11457200
TI  - The almost bottleable triplet carbene: 2,6-dibromo-4-tert-butyl-2',6'
      bis(trifluoromethyl)-4'-isopropyldiphenylcarbene.
AB  - Computations on 2,6-dibromo-4-tert-butyl-2',6'-bis(trifluoromethyl)-4'
      isopropyldiphenylcarbene (1) using ab initio and density functional theory
      methods underscore the unusual stability of the triplet over the singlet state.
      At the B3LYP/6-311G(d,p) level, the triplet state had a slightly bent central C-C
      C bond angle of 167 degrees, whereas this angle in the singlet was 134 degrees.
      The B3LYP singlet-triplet splitting (12.2 kcal/mol) was larger than that of the
      parent molecule (5.8 kcal/mol), diphenylcarbene (2), which also has a triplet
      ground state. The energy of a suitable isodesmic reaction showed the triplet and
      singlet states of (1) to be destabilized, by 6.3 and 12.5 kcal/mol, respectively,
      due to the combined effects of the CF3, Br, and alkyl substituents. The linear
      coplanar form of (3)(1), which might facilitate dimerization or electrophilic
      attack at the more exposed diradical center, was prohibitively (35.9 kcal/mol)
      higher in energy. Our results confirm Tomioka's conclusion that the triplet
      diarylcarbene, ortho-substituted with bulky CF3 and Br substituents, is
      persistent due to steric protection of the diradical center. Dimerization and
      other possible reaction pathways are inhibited, not only by the bulky ortho
      substituents but also by the para alkyl groups. The increase in stability of the
      triplet ((3)(1)) state relative to the singlet ((1)(1)) state does not influence
      the reactivity directly.

PMID- 11457201
TI  - Nitrogen abstraction from nitriles by osmium(IV) complexes.

PMID- 11457202
TI  - 13C detected scalar nitrogen-nitrogen couplings across the intramolecular
      symmetric NHN hydrogen bond of proton sponge.

PMID- 11457203
TI  - Electrochemically induced C-Br and C-I bond activation by the Pd3(dppm)3CO(2+)
      cluster, and characterization of the reactive Pd3(dppm)3CO(+) intermediate: the
      first confidently identified paramagnetic Pd cluster.

PMID- 11457204
TI  - Long-distance electron transfer across molecule-nanocrystalline semiconductor
      interfaces.

PMID- 11457205
TI  - Sol-gel synthesis of free-standing ferroelectric lead zirconate titanate
      nanoparticles.

PMID- 11457206
TI  - The coordination geometry of Np(VII) in alkaline solution.

PMID- 11457207
TI  - Cooperativity in amide hydrogen bonding chains: implications for protein-folding
      models.

PMID- 11457208
TI  - Enzymatic synthesis of carbon-fluorine bonds.

PMID- 11457209
TI  - Oxidative additions of E-E bonds (E = chalcogen) to group 10 metals: "tunable"
      cleavage of Se-Se bonds by Pt(0) complexes.

PMID- 11457210
TI  - Creation of an enantioselective hydrolase by engineered substrate-assisted
      catalysis.

PMID- 11457211
TI  - Solid-phase synthesis and asymmetric reactions of polymer-supported highly
      enantioenriched allylsilanes.

PMID- 11457212
TI  - Tandem enantioselective conjugate addition: electrophile trapping reactions.
      Application in the formation of syn or anti aldols.

PMID- 11457213
TI  - Langmuir-Blodgett nanorod assembly.

PMID- 11457214
TI  - A tethered disaccharide trapped as its anti conformer calibrates the Karplus
      relationship for 3J(C,H) coupling constants.

PMID- 11457215
TI  - Enol ether radical cation reaction kinetics. Laser flash photolysis calibration
      of radical cation clocks.

PMID- 11457216
TI  - Palladium-catalyzed hydroamination of 1,3-dienes: a colorimetric assay and
      enantioselective additions.

PMID- 11457217
TI  - Porous metal-organic polyhedra: 25 A cuboctahedron constructed from 12 Cu2(CO2)4
      paddle-wheel building blocks.

PMID- 11457218
TI  - New strategies in organic catalysis: the first enantioselective organocatalytic
      Friedel-Crafts alkylation.

PMID- 11457220
TI  - A photoactivatable prenylated cysteine designed to study isoprenoid recognition.
AB  - Protein prenylation, involving the alkylation of a specific C-terminal cysteine
      with a C(15) or C(20) isoprenoid unit, is an essential posttranslational
      modification required by most GTP-binding proteins for normal biological
      activity. Despite the ubiquitous nature of this modification and numerous efforts
      aimed at inhibiting prenylating enzymes for therapeutic purposes, the function of
      prenylation remains unclear. To explore the role the isoprenoid plays in
      mediating protein-protein recognition, we have synthesized a photoactivatable,
      isoprenoid-containing cysteine analogue (2) designed to act as a mimic of the C
      terminus of prenylated proteins. Photolysis experiments with 2 and RhoGDI (GDI),
      a protein which interacts with prenylated Rho proteins, suggest that the GDI is
      in direct contact with the isoprenoid moiety. These results, obtained using
      purified GDI as well as Escherichia coli (E. coli) crude extract containing GDI,
      suggest that this analogue will be an effective and versatile tool for the
      investigation of putative isoprenoid binding sites in a variety of systems.
      Incorporation of this analogue into peptides or proteins should allow for even
      more specific interactions between the photoactivatable isoprenoid and any number
      of isoprenoid binding proteins.

PMID- 11457221
TI  - Dihydroceramide delta(4) desaturase initiates substrate oxidation at C-4.
AB  - The intermolecular primary deuterium isotope effects on the individual C-H bond
      cleavage steps involved in dihydroceramide Delta(4) desaturation have been
      determined for the first time by incubating rat liver microsomes with 1:1
      mixtures of nonlabeled substrate and the appropriate regiospecifically
      dideuterated analogue. Analysis of the enzymatic products via gas chromatography
      coupled to mass spectrometry showed that the introduction of the (E) double bond
      between C-4 and C-5 occurs in two discrete steps: cleavage of the C4-H bond was
      found to be very sensitive to isotopic substitution (k(H)/k(D) = 8.0 +/- 0.8),
      while a negligible isotope effect (k(H)/k(D) = 1.02 +/- 0.07) was observed for
      the C5-H bond-breaking step. According to a mechanistic model that we have
      previously proposed, these results suggest that initial oxidation for this
      desaturation reaction occurs at C-4. This finding correlates nicely with the
      observation that 4-hydroxylated products are produced from a similar substrate by
      a closely related oxidative enzyme in yeast.

PMID- 11457222
TI  - Controlled expansion of a molecular cavity in a steroid host compound.
AB  - Expansion of a molecular cavity is described by using elongation of the side
      chain of a bile acid host compound. Bishomocholic acid (2), which has a side
      chain that is longer by two methylene unit than cholic acid (1), includes many
      organic substances at 1:1 host:guest ratios. X-ray crystallographic studies
      revealed that 2 has two types of open host frameworks: a bilayer type and a
      crossing type. Both of them are isostructural to those of 1, indicating that they
      are robust against the elongation of the side chain. In the former type, the
      increment of the width of the host channel corresponds to that of the length of
      the molecular structures. Larger aromatic guest components such as 1
      methylnaphthalene and 1-tetralone, are included in 2, but not in 1.

PMID- 11457223
TI  - A coiled coil with a fluorous core.
AB  - The design, synthesis, and structural characterization of a highly fluorinated
      peptide system based on the coiled coil region of the yeast transcription factor
      GCN4 is described. All four leucine residues (a position) and three valine
      residues (d position) were replaced by the unnatural amino acids 5,5,5
      trifluoroleucine and 4,4,4-trifluorovaline, respectively. The peptide is highly
      alpha-helical at low micromolar concentrations as judged by circular dichroism
      spectra, sediments as a dimeric species in the 5-30 microM concentration range,
      and exhibits a dimer melting temperature that is 15 degrees C higher than a
      control peptide with a hydrocarbon core. Furthermore, the apparent free energy of
      unfolding as calculated from guanidinium hydrochloride denaturation experiments
      is larger by approximately 1.0 kcal/mol for the fluorinated peptide than its
      hydrocarbon counterpart. We conclude that additional stability is derived from
      sequestering the more hydrophobic trifluoromethyl groups from aqueous solvent.
      These studies introduce a new paradigm in the design of molecular self-assembling
      systems, one based on orthogonal solubility properties of liquid phases.

PMID- 11457224
TI  - Direct observation of radical intermediates in protein-dependent DNA charge
      transport.
AB  - Charge migration through the DNA base stack has been probed both
      spectroscopically, to observe the formation of radical intermediates, and
      biochemically, to assess irreversible oxidative DNA damage. Charge transport and
      radical trapping were examined in DNA assemblies in the presence of a site
      specifically bound methyltransferase HhaI mutant and an intercalating ruthenium
      photooxidant using the flash-quench technique. The methyltransferase mutant,
      which can flip out a base and insert a tryptophan side chain within the DNA
      cavity, is found to activate long-range hole transfer through the base pair
      stack. Protein-dependent DNA charge transport is observed over 50 A with guanine
      radicals formed >10(6) s(-1); hole transport through DNA over this distance is
      not rate-limiting. Given the time scale and distance regime, such protein
      dependent DNA charge transport chemistry requires consideration physiologically.

PMID- 11457225
TI  - Self-assembly and gelation of oxidized glutathione in organic solvents.
AB  - The oxidized disulfide form of the ubiquitous tripeptide glutathione (gamma-glu
      cys-gly) (GSSG) is shown to produce transparent, thermoreversible gels in aqueous
      solutions of dimethyl sulfoxide, dimethylformamide, and methanol, at GSSG
      concentrations as low as 1.5 mM. The gels bind Congo Red and exhibit dramatic
      green birefringence when observed between crossed polarizers, characteristic of
      amyloid structures. By transmission electron microscopy, the gels appear to
      consist of a network of fibrous structures about 75 nm in diameter. Several
      structurally related peptides, including the glutathione isomer glu-cys-gly and
      the aspartyl analogue of glutathione (beta-asp-cys-gly), failed to produce gels
      under similar conditions. These results suggest that the interactions which
      produce gelation are highly specific and that the unusual peptide geometry
      introduced by gamma-glu-cys linkage is critical to the gelation behavior. (1)H
      NMR indicates solvent-dependent perturbation of the gamma-glutamyl alpha- and
      beta-protons and circular dichroism reveals a shift in the geometry of the
      disulfide bond under conditions producing gelation. We propose that in
      appropriate organic solvents, GSSG self-assembles into an extended network of
      beta-sheetlike structures capable of immobilizing bulk solvent. While obviously
      speculative, it is interesting to consider possible physiological consequences of
      glutathione self-recognition in such processes as abnormal protein aggregation
      and the thiol-disulfide exchange which is believed to participate in protein
      folding.

PMID- 11457226
TI  - First synthesis of phenylazomethine dendrimer ligands and structural studies.
AB  - Novel dendritic polyphenylazomethines (DPAs), which consist of a pi-conjugated
      backbone, were synthesized up to the fourth generation by the convergent method
      via dehydration of aromatic ketones with aromatic amines in the presence of
      titanium(IV) tetrachloride. The obtained dendrimers, DPA G1-4 (designated as GX,
      where X is the generation number), show high thermostability (Td(10%) 521 degrees
      C in DPA G4) and high solubility for the common solvents such as chloroform, THF,
      and DMSO unlike the conventional linear polyphenylazomethines, which have very
      low solubilities. The DPA G4 molecule was confirmed to have a spherelike
      structure by GPC measurement and a molecular model based on the crystal structure
      of DPA G2. Crystal data for DPA G2: monoclinic space group P2(1)/a, a = 25.352(4)
      A, b = 8.577(2) A, c = 16.151(2) A, beta = 106.25(1) degrees, V = 3371.6(10)
      A(3), Z = 2, D(calc) = 1.168 g/cm(3), mu(Cu Kalpha) = 0.536 cm(-1), final R =
      0.089, and R(w) = 0.287. The molecular modeling reveals that a DPA G4 molecule
      has a spherelike structure, in which the height, width, and depth are 2.3, 2.9,
      and 2.5 nm, respectively. The TEM and AFM pictures show the DPA G4 molecules to
      have a spherelike structure (the diameter: 2.3 nm) and are regularly assembled on
      a plate by casting. The occupied area of one DPA G4 molecule in a monolayer on
      water was estimated by pi-A measurements to be 3.8-4.2 nm(2) (the calculated
      diameter 2.2-2.3 nm, which agreed with the TEM result). NMR studies (1H NMR at
      130 degrees C and T(1) measurements) supported a conformational rigidity of DPA
      G4 in solution.

PMID- 11457227
TI  - The generality of architectural isomerism in designer inclusion frameworks.
AB  - We describe herein new structural isomers of a lamellar host system based on
      organodisulfonate "pillars" that connect opposing hydrogen-bonded sheets,
      consisting of topologically complementary guanidinium (G) ions and sulfonate (S)
      groups, to generate inclusion cavities between the sheets. These new isomers
      zigzag brick, double brick, V-brick, and crisscross bilayer-expand significantly
      on our earlier report of architectural isomerism displayed by the discrete
      bilayer and simple brick forms. We demonstrate here that the discrete bilayer
      simple brick isomerism, which was limited to several host-guest combinations
      based on the G(2)(4,4'-biphenyldisulfonate) host and one pair of compounds based
      on the G(2)(2,6-naphthalenedisulfonate), can be generalized to other
      organodisulfonate pillars. Furthermore, in many cases the selectivity toward the
      different framework isomers reflects a rather systematic templating role of the
      guest molecules and host-guest recognition during assembly of the lattice. We
      also describe a convenient approach to identifying and classifying the
      innumerable possible host architectures based upon the pillar projection
      topologies for the GS sheets and the intersheet connectivities. The discovery of
      these new architectures reveals a structural versatility for this class of
      materials that exceeds initial expectations and observations. Each topology
      produces different connectivities between the sheets in the third dimension that
      endows each framework isomer with uniquely shaped and sized inclusion cavities,
      enabling this host system to conform readily to different guests. The unlimited
      number of architectures available, combined with the inherent conformational
      softness and structural tunability of these host lattices, suggests a near
      universality for the GS system with respect to guest inclusion.

PMID- 11457228
TI  - Inclusion compounds of tetrakis(4-nitrophenyl)methane: C-H...O networks,
      pseudopolymorphism, and structural transformations.
AB  - Tetrakis(4-nitrophenyl)methane is a new host material with considerable
      structural adaptability over a range of solvents. The crystal structures of 14 of
      these solvates have been determined and classified into three groups. The
      diamondoid group, wherein the host molecules form a 2-fold interpenetrated
      diamondoid network structure, is unprecedented in that network connections are
      made exclusively with weak C-H...O and pi...pi interactions. This group consists
      of the solvates of THF, dioxane, nitrobenzene, 4-bromoanisole, anisole,
      phenetole, p-xylene, and chlorobenzene. The rhombohedral group, which is
      characterized by specific host.guest interactions of the C-H...O and
      halogen...O2N type, consists of the solvates of CHCl3 and CHBr3 and somewhat
      surprisingly DMF, which shows an unusual 3-fold disorder mimicking in part the
      shape and size of the haloform molecules though not their orientation. The third
      group comprises solvent-rich solvates of the host with mesitylene, collidine, and
      o-xylene with quite different crystal structures. The THF solvate was found to
      lose solvent over limited temperature ranges transforming reversibly from the
      diamondoid structure to the rhombohedral structure. A mechanism for this process
      is outlined. Material from which solvent has been removed by heating was also
      found to resolvate upon soaking in appropriate solvents. In summary, the title
      compound forms a host network that is partially robust and in part flexible. It
      is possible that this fluxional nature of the host network derives from the
      weakness of the connecting interactions.

PMID- 11457229
TI  - Is there stereoelectronic control in hydrolysis of cyclic guanidinium ions?
AB  - To assess stereoelectronic effects in the cleavage of tetrahedral intermediates,
      a series of five-, six-, and seven-membered cyclic guanidinium salts was
      synthesized. If stereoelectronic control by antiperiplanar lone pairs is
      operative, these are expected to hydrolyze with endocyclic C-N cleavage to
      acyclic ureas. However, hydrolysis in basic media produces mixtures of cyclic and
      acyclic products, as determined by 1H NMR analysis. The results show that in the
      six-membered ring antiperiplanar lone pairs provide a weak acceleration of the
      breakdown of the tetrahedral intermediate, but in five- and seven-membered rings
      there is no evidence for such acceleration, which instead can be provided by syn
      lone pairs.

PMID- 11457230
TI  - Stereoelectronic control in addition of nucleophiles to an amidinium ion.
AB  - Nucleophilic addition to 1,3-dimethyl-5-phenyl-1,4,5,6-tetrahydropyrimidinium ion
      provides a quantitative measure of stereoelectronic control. This amidinium ion
      presents the nucleophile with two distinct paths for attack. Axial attack is
      favored by interaction between the orbital of the developing bond and
      antiperiplanar lone pairs on the nitrogens. Reaction of the amidinium salt with
      diverse nucleophiles (D(-), H3C(-), n-Bu(-), PhCH2(-), allyl(-), Ph(-), C5F6(-),
      CH2=CH(-), HC triple bond C(-), PhC triple bond C(-), CN(-)) produces mixtures of
      cis and trans stereoisomers. Both kinetic and thermodynamic product distributions
      were measured by 1H NMR, before and after acid-catalyzed equilibration. The
      values provide insight into the roles of steric and stereoelectronic forces at
      the transition state and in products. Stereoelectronic effects on reactivity are
      found to be weak (ca. 1 kcal/mol).

PMID- 11457231
TI  - Cis-trans isomerization of polyunsaturated fatty acid residues in phospholipids
      catalyzed by thiyl radicals.
AB  - Phospholipids containing trans-unsaturated fatty acid residues are the major
      products of the thiyl radical attack on L-alpha-phosphatidylcholine from soybean
      lecithin in homogeneous solution or in liposomes (LUVET). Thiyl radicals act as
      the catalyst for the cis-trans isomerization, and the number of catalytic cycles
      depends on the reaction conditions. The presence of approximately 0.2 mM oxygen
      does not influence the reaction outcome but accelerates the efficiency of cis
      trans isomerization in homogeneous solution. Under these conditions, the PUFA
      peroxidation is found to be unimportant. A detailed study of the isomerization of
      methyl linoleate including product studies indicates the formation of a small
      amount of conjugated dienes that act as inhibitors. Indeed, all-trans-retinol
      substantially retarded the isomerization process.

PMID- 11457232
TI  - Total syntheses and biological investigations of tamandarins A and B and
      tamandarin A analogs.
AB  - Tamandarins A (1) and B (2), two natural products similar in structure to
      didemnin B (3), were recently isolated from a Brazilian marine ascidian of the
      family Didemnidae. The cytotoxicity of 1 was reported to be somewhat more potent
      in vitro than that of 3 against various human cancer cell lines. The present
      account describes the first total syntheses of 1 and 2, and the syntheses of
      tamandarin A side chain analogues. The cytotoxicity data for these compounds show
      that the side chain modifications exhibit a parallel effect for both didemnins
      and tamandarins. This observation supports tamandarins' role as didemnins' mimic.

PMID- 11457233
TI  - Enantiospecific synthesis of the proposed structure of the antitubercular marine
      diterpenoid pseudopteroxazole: revision of stereochemistry.
AB  - An enantiospecific synthesis of structure 1, previously assigned to the
      antitubercular marine natural product pseudopteroxazole, has been accomplished as
      outlined in Scheme 1. Coupling of diene acid 3 and amino phenol 4 produced the
      amide 5, which was subjected to a novel oxidative intramolecular Diels-Alder
      reaction to generate the tricyclic lactam 6a stereoselectively. This product was
      transformed via intermediates 7-11 into the diene 13. Cationic cyclization of 13
      afforded two diastereomeric tricyclic amphilectanes which were separated and
      transformed by parallel four-step sequences into 1 and 2, respectively. Neither 1
      nor 2 were identical with pseudopteroxazole, indicating a need for revision of
      the structure, probably to 16.

PMID- 11457234
TI  - Enantioselective and diastereoselective Mukaiyama-Michael reactions catalyzed by
      bis(oxazoline) copper(II) complexes.
AB  - The scope of highly enantioselective and diastereoselective Michael additions of
      enolsilanes to unsaturated imide derivatives has been developed with use of
      [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these
      additions are useful synthons that contain termini capable of differentiation
      under mild conditions. Michael acceptor pi-facial selectivity is consistent with
      two-point binding of the imide substrate and can be viewed as an extension of
      substrate enantioselection in the corresponding Diels-Alder reactions. A model
      analogous to the one employed to describe the hetero Diels-Alder reaction is
      proposed to account for the observed relation between enolsilane geometry and
      product absolute diastereocontrol. Insights into modes of catalyst inactivation
      are given, including spectroscopic evidence for inhibition of the catalyst by a
      dihydropyran intermediate that evolves during the course of the reaction. A
      procedure is disclosed in which an alcohol additive is used to hydrolyze the
      inhibiting dihydropyran and afford the desilylated Michael adduct in
      significantly shortened reaction time.

PMID- 11457235
TI  - Teubrevin G and teubrevin H: the first total syntheses of rearranged neo
      clerodanes including solutions to the problems of chirality merger and furan ring
      assembly.
AB  - Total syntheses of teubrevins G (2) and H (3) are described. The reported
      strategy relies on a highly regioselective cycloaddition-fragmentation approach
      to the construction of a 2,3,4-trisubstituted furan and features efficient ring
      closing metathesis chemistry made possible through the application of a 1,3
      dimesityl-4,5-dihydroimidazol-2-ylideneruthenium precatalyst. The key building
      blocks 39 and 48 were constructed by asymmetric processes and coupled under
      conditions where good remote asymmetric induction was realized. The
      diastereoselection observed in this alkylation reaction appears to be intimately
      associated with the conformational properties of the beta-keto ester enolate.
      While the readily separated major diastereomer was transformed via a short route
      to 2, the minor component served as the precursor to 3. The efficiency of the
      synthesis was thereby well served.

PMID- 11457236
TI  - Phase separation in AlxGa1-xAs nanowhiskers grown by the solution-liquid-solid
      mechanism.
AB  - Low-temperature growth of AlxGa1-xAs by the solution-liquid-solid mechanism
      affords nanowhiskers having two specific overall compositions: x = 0.1 and 0.8.
      Intermediate compositions (0.1 < x < 0.8) are inaccessible by the method
      employed. Examination of the nanowhiskers by transmission electron microscopy,
      photoluminescence spectroscopy, electron energy loss spectroscopy, and annealing
      studies indicates that they possess compositionally modulated nanostructures. The
      observed compositional modulation consists of alternating comparatively Al-rich
      and Ga-rich AlxGa1-xAs domains with dimensions of 3-20 nm. The spontaneous phase
      separation, which occurs during growth, appears to be kinetically driven, and the
      resulting phase-separated nanostructures appear to be, therefore, metastable
      rather than stable. Spontaneous phase separation in AlxGa1-xAs, which strongly
      influences its photoemission behavior, is not well understood theoretically.

PMID- 11457237
TI  - Synthesis, structure, and bonding of open-shell Sr3In5: an unusual electron
      deficiency in an indium network, beyond the Zintl boundary.
AB  - The new title compound has been synthesized and characterized by physical
      property measurements and electronic structure calculations. The results ratify
      the highly uncommon deficiency of one electron that has been long speculated for
      its Ca3Ga5-type structure on the basis of the simple Zintl electron counting
      formalism. In the Sr3In5 structure (Cmcm), 4- and 2-bonded indium atoms in a 4:1
      ratio form a three-dimensional classical network that encapsulates strontium
      atoms in its narrow channels. The electrical conductivity of the compound shows
      typical metallic behavior. The detailed electronic structure analysis suggests
      that the electron hole is mainly localized on a nonbonding p-orbital on the 2
      bonded indium atoms, and that these orbitals, stacked in a sigma-type way along
      avector (4.97 A), interact only weakly with each other to form highly one
      dimensional bands.

PMID- 11457238
TI  - Molecularly ordered inorganic frameworks in layered silicate surfactant
      mesophases.
AB  - Self-assembled lamellar silica-surfactant mesophase composites have been prepared
      with crystal-like ordering in the silica frameworks using a variety of cationic
      surfactant species under hydrothermal conditions. These materials represent the
      first mesoscopically ordered composites that have been directly synthesized with
      structure-directing surfactants yielding highly ordered inorganic frameworks. One
      dimensional solid-state 29Si NMR spectra, X-ray diffraction patterns, and
      infrared spectra show the progression of molecular organization in the self
      assembled mesophases from structures with initially amorphous silica networks
      into sheets with very high degrees of molecular order. The silicate sheets appear
      to be two-dimensional crystals, whose structures and rates of formation depend
      strongly on the charge density of the cationic surfactant headgroups. Two
      dimensional solid-state heteronuclear and homonuclear NMR measurements show the
      molecular proximities of the silica framework sites to the structure-directing
      surfactant molecules and establish local Si-O-Si bonding connectivities in these
      materials.

PMID- 11457239
TI  - Stability of Zn(II) cations in chabazite studied by periodical density functional
      theory.
AB  - The location of the Zn(2+) cation in Zn-exchanged chabazite has been studied by
      the periodical density functional method. Chabazite was chosen as a zeolite
      model, because it contains three different types of rings commonly found in the
      zeolite structures: four-, six-, and eight-membered rings. Two aluminum atoms
      have been employed to substitute the silicon atoms in the same D6R unit cell of
      the zeolite framework. This leads to different arrangements for the Bronsted site
      pair and the Zn(II) cation. The two Bronsted sites are found to be more stable
      when placed in the small ring (4T ring) than in the other rings. This suggests
      that the most reactive Bronsted sites are located in the large rings. Two
      Bronsted sites are most stable when the O(H)-Al-O-Si-O(H)-Al sequence is followed
      in the same ring instead of being located in two different rings. This resembles
      the aluminum distribution in the small four-membered ring and agrees with bond
      order conservation rules. The cation stability is markedly influenced by the
      distortions of the framework. Other factors that also contribute to the
      stabilization are the aluminum content near the cation and the stability of the
      original Bronsted sites. The Zn(2+) cation is more stable in the large rings than
      in the small ones, the six-membered one being the most stable configuration. In
      the small rings, the cation is, therefore, more reactive. Two different probe
      molecules have been used to study the interaction with the Zn(II) cation: water
      and methane. These probe molecules can extract the active center from its
      original position. For the water molecule, this effect is large and leads to a
      high framework relaxation. The value of the binding energy of this molecule to
      the active sites is influenced by these framework relaxations as well as by the
      cationic position environment. For weakly interacting methane, these effects are
      significantly less.

PMID- 11457240
TI  - Covalent modification of iron surfaces by electrochemical reduction of
      aryldiazonium salts.
AB  - Electrochemical reduction of aryldiazonium salts (in acetonitrile or acidic
      aqueous medium) on an iron or mild steel surface permits the strong bonding
      (which resists an ultrasonic cleaning) of aryl groups on these surfaces.
      Attachment of aryl groups was demonstrated by the combined used of
      electrochemistry, infrared spectroscopy and polarization modulation infrared
      reflection spectroscopy (PMIRRAS), Rutherford backscattering, X-ray photoelectron
      spectroscopy, and capacity measurements. The substituents of aryl groups, which
      can be widely varied, include NO2, I, COOH, and long alkyl chains. It is shown
      that the attachment of the aryl groups is to an iron and not to an oxygen atom
      and that the bond is covalent.

PMID- 11457241
TI  - Chlorine kinetic isotope effects on the haloalkane dehalogenase reaction.
AB  - We have found chlorine kinetic isotope effects on the dehalogenation catalyzed by
      haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 to be 1.0045 +/-
      0.0004 for 1,2-dichloroethane and 1.0066 +/- 0.0004 for 1-chlorobutane. The
      latter isotope effect approaches the intrinsic chlorine kinetic isotope effect
      for the dehalogenation step. The intrinsic isotope effect has been modeled using
      semiempirical and DFT theory levels using the ONIOM QM/QM scheme. Our results
      indicate that the dehalogenation step is reversible; the overall irreversibility
      of the enzyme-catalyzed reaction is brought about by a step following the
      dehalogenation.

PMID- 11457242
TI  - Probing slow time scale dynamics at methyl-containing side chains in proteins by
      relaxation dispersion NMR measurements: application to methionine residues in a
      cavity mutant of T4 lysozyme.
AB  - A relaxation dispersion-based NMR experiment is presented for the measurement and
      quantitation of micros-ms dynamic processes at methyl side-chain positions in
      proteins. The experiment measures the exchange contribution to the 13C line
      widths of methyl groups using a constant-time CPMG scheme. The effects of cross
      correlated spin relaxation between dipole-dipole and dipole-CSA interactions as
      well as the effects of scalar coupling responsible for mixing of magnetization
      modes during the course of the experiment have been investigated in detail both
      theoretically and through simulations. It is shown that the complex relaxation
      properties of the methyl spin system do not complicate extraction of accurate
      exchange parameters as long as care is taken to ensure that appropriate
      magnetization modes are interchanged in the middle of the constant-time CPMG
      period. An application involving the measurement of relaxation dispersion
      profiles of methionine residues in a Leu99Ala substitution of T4 lysozyme is
      presented. All of the methionine residues are sensitive to an exchange event with
      a rate on the order of 1200 s(-1) at 20 degrees C that may be linked to a process
      in which hydrophobic ligands are able to rapidly bind to the cavity that is
      present in this mutant.

PMID- 11457243
TI  - A comprehensive analysis of multifield 15N relaxation parameters in proteins:
      determination of 15N chemical shift anisotropies.
AB  - This study deals with the exploitation of the three classical 15N relaxation
      parameters (the longitudinal relaxation rate, R1, the transverse relaxation rate,
      R2, and the 1H-15N cross-relaxation rate, sigmaNH) measured at several magnetic
      fields in uniformly 15N-labeled proteins. Spectral densities involved in R1, R2
      and sigmaNH are analyzed according to the functional form A + B/(1 + omega(2)
      taus(2)), where taus is the correlation time associated with slow motions sensed
      by the NH vector at the level of the residue to which it belongs. The coefficient
      B provides a realistic view of the backbone dynamics, whereas A is associated
      with fast local motions. According to the "model free approach", B can be
      identified with 2tausS(2) where S is the generalized order parameter. The
      correlation time taus is determined from the field dependency of the relaxation
      parameters while A and B are determined through linear equations. This simple
      data processing is needed for obtaining realistic error bars based on a
      statistical approach. This proved to be the key point for validating an extended
      analysis aiming at the determination of nitrogen chemical shift anisotropy. The
      protein C12A-p8(MTCP1) has been chosen as a model for this study. It will be
      shown that all data (obtained at five magnetic field strengths corresponding to
      proton resonance of 400, 500, 600, 700, and 800 MHz) are very consistently fitted
      provided that a specific effective correlation time associated with slow motions
      is defined for each residue. This is assessed by small deviations between
      experimental and recalculated values, which, in all cases, remain within
      experimental uncertainty. This strategy makes needless elaborate approaches based
      on the combination of several slow motions or their possible anisotropy. Within
      the core of the protein taus fluctuates in a relatively narrow range (with a mean
      value of 6.15 ns and a root-mean-square deviation of 0.36 ns) while it is
      considerably reduced at the protein extremities (down to approximately 3 ns). To
      a certain extent, these fluctuations are correlated with the protein structure. A
      is not obtained with sufficient accuracy to be valuably discussed. Conversely,
      order parameters derived from B exhibit a significant correlation with the
      protein structure. Finally, the multi-field analysis of the evolution of
      longitudinal and transverse relaxation rates has been refined by allowing the 15N
      chemical shift anisotropy (csa) to vary residue by residue. Within uncertainties
      (derived here on a statistical basis) an almost constant value is obtained. This
      strongly indicates an absence of correlation between the experimental value of
      this parameter obtained for a given residue in the protein, the nature of this
      residue, and the possible involvement of this residue in a structured area of the
      protein.

PMID- 11457244
TI  - Elucidation of structure and location of V(IV) ions in heteropolyacid catalysts
      H4PVMo11O40 as studied by hyperfine sublevel correlation spectroscopy and pulsed
      electron nuclear double resonance at W- and X-band frequencies.
AB  - Electron spin resonance, pulsed electron nuclear double resonance (ENDOR)
      spectroscopy at W- and X-band frequencies, and hyperfine sublevel correlation
      (HYSCORE) spectroscopy have been employed to determine the location of the V(IV)
      ions in H4PVMo11O40 heteropolyacid catalysts. In these materials the
      heteropolyanions have the well-known structure of the Keggin molecule.
      Interactions of the unpaired electrons of the paramagnetic vanadyl ions (VO(2+))
      with all relevant nuclei 1H, 31P, and 51V) could be resolved. The complete
      analysis of the hyperfine coupling tensor for the phosphorus nucleus in the
      fourth coordination sphere of the V(IV) ion allowed for the first time a detailed
      structural analysis of the paramagnetic ions in heteropolyacids in hydrated and
      dehydrated catalysts. The 31P and 1H ENDOR results show that V(IV) ions are
      incorporated as vanadyl pentaaqua complexes [VO(H2O)5](2+) in the void space
      between the heteropolyanions in the hydrated heteropolyacid. For the dehydrated
      H4PVMo11O40 materials the distance between the V(IV) ion and the central
      phosphorus atom of the Keggin molecule could be determined with high accuracy on
      the basis of orientation-selective 31P ENDOR experiments and HYSCORE
      spectroscopy. The results give a first direct experimental evidence that the
      paramagnetic vanadium species are not incorporated at molybdenum sites into the
      Keggin structure of H4PVMo11O40 and also do not act as bridges between two Keggin
      units after calcination of the catalyst. The vanadyl species are found to be
      directly attached to the Keggin molecules. The VO(2+) ions are coordinated to
      four or three outer oxygen atoms from one PVMo11 heteropolyanion in a trigonal
      pyramidal or slightly distorted square-pyramidal coordination geometry,
      respectively.

PMID- 11457245
TI  - Molecular adsorption onto metallic quantum wires.
AB  - We have studied the adsorption of mercaptopropionic acid, 2,2'-bipyridine, and
      dopamine onto electrochemically fabricated Cu nanowires. The nanowires are
      atomically thin with conductance quantized near integer multiples of 2e(2)/h.
      Upon molecular adsorption, the quantized conductance decreases to a fractional
      value, due to the scattering of the conduction electrons by the adsorbates. The
      decrease is as high as 50% for the thinnest nanowires whose conductance is at the
      lowest quantum step, and smaller for thicker nanowires with conductance at higher
      quantum steps. The adsorbate-induced conductance changes depend on the binding
      strengths of the molecules to the nanowires, which are in the order of
      mercaptopropionic acid, 2,2'-bipyridine, and dopamine, from strongest to weakest.
      The sensitive dependence of the quantized conductance on molecular adsorption may
      be used for molecular detection.

PMID- 11457246
TI  - Reactions of 1,3-cyclohexadiene with singlet oxygen. A theoretical study.
AB  - A thorough study of the reaction of singlet oxygen with 1,3-cyclohexadiene has
      been made at the B3LYP/6-31G(d) and CASPT2(12e,10o) levels. The initial addition
      reaction follows a stepwise diradical pathway to form cyclohexadiene endoperoxide
      with an activation barrier of 6.5 kcal/mol (standard level = CASPT2(12e,10o)/6
      31G(d); geometries and zero-point corrections at B3LYP/6-31G(d)), which is
      consistent with an experimental value of 5.5 kcal/mol. However, as the enthalpy
      of the transition structure for the second step is lower than the diradical
      intermediate, the reaction might also be viewed as a nonsynchronous concerted
      reaction. In fact, the concertedness of the reaction is temperature dependent
      since entropy differences create a free energy barrier for the second step of 1.8
      kcal/mol at 298 K. There are two ene reactions; one is a concerted mechanism
      (DeltaH(double dagger) = 8.8 kcal/mol) to 1-hydroperoxy-2,5-cyclohexadiene (5),
      while the other, which forms 1-hydroperoxy-2,4-cyclohexadiene (18), passes
      through the same diradical intermediate (9) as found on the pathway to
      endoperoxide. The major pathway from the endoperoxide is O-O bond cleavage (22.0
      kcal/mol barrier) to form a 1,4-diradical (25), which is 13.9 kcal/mol less
      stable than the endoperoxide. From the diradical, two low-energy pathways exist,
      one to epoxyketone (29) and the other to the diepoxide (27), where both products
      are known to be formed experimentally with a product ratio sensitive to the
      nature of substitutents. A significantly higher activation barrier leads to C-C
      bond cleavage and direct formation of maleic aldehyde plus ethylene.

PMID- 11457247
TI  - beta-Borylallylsilanes as a new tool for convenient synthesis of alkenylboranes.

PMID- 11457248
TI  - Ag(P4)2(+): the first homoleptic metal-phosphorus cation.

PMID- 11457249
TI  - The first doubly borylated enolate as an intermediate of the double aldol
      reaction.

PMID- 11457250
TI  - Intramolecular Diels-Alder reactions employing hydroxamate tethers: the first
      examples and promising prospects.

PMID- 11457251
TI  - Regio- and diastereoselective tandem rhodium-catalyzed allylic alkylation/Pauson
      Khand annulation reactions.

PMID- 11457252
TI  - Oxidative N-dealkylation of a carboxylate-bridged diiron(II) precursor complex by
      reaction with O2 affords the elusive [Fe2(mu-OH)2(mu-O2CR)](3+) core of soluble
      methane monooxygenase hydroxylase.

PMID- 11457253
TI  - Tautomerization dynamics of a model base pair in DNA.

PMID- 11457254
TI  - Release of nitric oxide from S-nitrosohemoglobin. Electron transfer as a response
      to deoxygenation.

PMID- 11457255
TI  - Polymerization of a phosphonium diene amphiphile in the regular hexagonal phase
      with retention of mesostructure.

PMID- 11457257
TI  - Observation of unusual kinetics in Heck reactions of aryl halides: the role of
      non-steady-state catalyst concentration.

PMID- 11457256
TI  - Protein purification and function assignment of the epoxidase catalyzing the
      formation of fosfomycin.

PMID- 11457258
TI  - Terminal amido and imido complexes of three-coordinate nickel.

PMID- 11457259
TI  - 5-Pyrimidinols: novel chain-breaking antioxidants more effective than phenols.

PMID- 11457261
TI  - Novel [2+2+2]annulation of 1,6-diynes mediated by methallylchromate or
      methallylmagnesium chloride under CrCl3 catalysis.

PMID- 11457260
TI  - Two-dimensional, shell-cross-linked nanoparticle arrays.

PMID- 11457262
TI  - Interconversion of monohydride intermediates in Rh(I)-catalyzed asymmetric
      hydrogenation of dimethyl 1-benzoyloxyethenephosphonate.

PMID- 11457263
TI  - SEA-TROSY (solvent exposed amides with TROSY): a method to resolve the problem of
      spectral overlap in very large proteins.

PMID- 11457264
TI  - Model hemoprotein reduction potentials: the effects of histidine-to-iron
      coordination equilibrium.

PMID- 11457265
TI  - Spectroscopic evidence for nitric oxide binding with cob(II)alamin.

PMID- 11457266
TI  - Kinetic resolution of an organozinc reagent: in situ formation of an
      enantioenriched allenylzinc species.

PMID- 11457267
TI  - Palladium-catalyzed arylation of ethyl cyanoacetate. Fluorescence resonance
      energy transfer as a tool for reaction discovery.

PMID- 11457268
TI  - Tetradecafluorosexithiophene: the first perfluorinated oligothiophene.

PMID- 11457269
TI  - Modeling of N(d) and N(Col) phase transitions in discotic side chain polymers by
      the extended McMillan theory.

PMID- 11457270
TI  - Supramolecular honeycomb by self-assembly of molecular rods in rod-coil molecule.

PMID- 11457271
TI  - [Ga2(DETA)(PO4)2]-2H2O (DETA = diethylenetriamine): a novel porous gallium
      phosphate containing 24-ring channels.

PMID- 11457272
TI  - Signal processing at the molecular level.

PMID- 11457273
TI  - Hybridization between oxy-peptide nucleic acids and DNAs: dependence of hybrid
      stabilities on the chain-lengths, types of base pairs, and the chain directions.
AB  - Oxy-peptide nucleic acids (OPNAs) of [-NH-CH(CH2-CH2-Base)-CH2-O-CH2-CO-]-type
      main chain with four different types of nucleobases (Base = A, G, C, and U) or
      with an abasic side group (X) were synthesized. Melting curves of the 1:1 hybrids
      of o(A(n))-d(Tn)) pairs with n = 6, 9, 12, and 15 showed very sharp transitions
      at high Tm values, particularly for long chains, indicating that nearly optimum
      matching is attained in the structure of the o(A(n))-d(Tn) hybrids. Effect of
      different types of base pairs on the hybrid stabilities was examined for the
      o(A4NA4)-d(T4N'T4) 1:1 mixtures where N is A, G, C, U, or X and N' is A, G, C, or
      T. In all series of the hybrids the complementary pairs showed the highest Tm
      values. The Tm values of the complementary pairs were about 35 degrees C when
      purine bases were inserted as the N group in the OPNA, but they were 20-23
      degrees C when pyrimidine bases were inserted. The melting curves of the hybrids
      with a single mismatch were similar to those with a single X-N' pair, suggesting
      that the mismatch base pairs have been ignored in the hybrids. All complementary
      OPNA-DNA hybrids showed higher Tm values and sharper transitions than the
      corresponding DNA-DNA hybrids. The OPNA-DNA hybrids favor a parallel direction
      i.e., the N-terminal of OPNA is directed to the 5'-terminal of DNA.

PMID- 11457274
TI  - Cavitand-porphyrins.
AB  - The synthesis and characterization of new nanoscale container molecules 7 and 8
      are described. They are covalent hybrids of deepened, self-folding cavitands and
      metalloporphyrins. In receptor 7, the Zn-porphyrin wall is directly built onto
      the cavitand skeleton. Host 8 features a large unimolecular cavity containing two
      cavitands attached with the Zn-porphyrin wall. Its dimensions, approximately 10 x
      25 A, place it among the largest synthetic hosts prepared to date. A series of
      adamantyl- and pyridyl-containing guests 14-20 of various lengths were prepared
      and used to determine the hosts' binding abilities in solution using UV/vis and
      (1)H NMR spectroscopy. Intramolecular hydrogen bonds at the upper rims of the
      cavitands resist the unfolding of the inner cavities and thereby increase the
      energetic barrier to guest exchange. The exchange is slow on the NMR time scale
      (at < or =300 K), and kinetically stable complexes result. When the cavities and
      metalloporphyrins participate simultaneously in the binding event, very high
      affinities for guests are found (-DeltaG295 up to 10 kcal x mol(-1) in toluene),
      to which the porphyrin fragments contribute significantly (-DeltaG295 up to 6
      kcal x mol(-1)). The pairwise selection of two different guests by molecular
      container 8 is reported, and the termolecular complex formed raises the
      possibility of metal-catalyzed bimolecular reactions in these containers.

PMID- 11457275
TI  - Structure and conformation of DAB dendrimers in solution via multidimensional NMR
      techniques.
AB  - NOESY-HSQC 3D-NMR and NOESY 2D-NMR techniques have been used on a 750 MHz
      spectrometer to study the chain conformations of different generation DAB
      dendrimers (poly[propylene imine] dendrimers) in chloroform and benzene
      solutions. The high-field multidimensional NMR techniques provided the chemical
      shift dispersion needed to resolve all of the unique resonances in the
      dendrimers. By studying the NOE interactions among dendritic chain protons,
      information about through space interactions between protons on different parts
      of the dendrimer chain is obtained, which is directly related to the conformation
      of the dendrimer. These experiments also give further proof of the chemical shift
      assignments obtained from the HMQC-TOCSY 2D and 3D NMR experiments. The
      concentration effects on chemical shifts have also been observed, revealing
      information about the interactions between solvent and different parts of
      dendrimer molecules. These studies clearly show for DAB dendrimers, that folded
      chain conformations can occur in nonpolar solvents such as benzene and extended
      chain conformations are predominant in polar solvents such as chloroform.

PMID- 11457276
TI  - Computational analysis of the autocatalytic posttranslational cyclization
      observed in histidine ammonia-lyase. A comparison with green fluorescent protein.
AB  - Density functional calculations using hybrid functionals (B3LYP) have been
      performed to study the mechanism of the autocatalytic posttranslational
      cyclization observed in histidine ammonia-lyase. Two mechanisms were analyzed,
      the commonly accepted mechanism in which cyclization precedes dehydrogenation
      (reduced mechanism) and a mechanism in which dehydrogenation precedes cyclization
      (oxidized mechanism). The reduced pathway is not supported by the calculations,
      while the alternative oxidized mechanism where a dehydration occurs prior to the
      formation of the ring yields reasonable energetics for the system. Database
      searches showed that the oxidative mechanism in which the formation of the
      dehydro amino acids in residue i + 1 precedes the cyclization is also
      structurally advantageous as it results in shorter distances between the carbonyl
      carbon of residue i and the amide nitrogen of residue i + 2 and, therefore,
      preorganizes the protein for cyclization. Conformational searches showed that
      these distances were also unusually short and exhibited very little variation in
      the Delta-Ala143 HAL tetramer, indicating that like GFP the tetrameric form of
      HAL is rigidly preorganized for cyclization. The monomeric form of HAL is less
      preorganized than the tetrameric form of HAL. Dehydro amino acids aid in the
      preorganization, but the main driving force in the rigid tight turn formation is
      the influence of the surrounding protein.

PMID- 11457277
TI  - Evaluation of the catalytic mechanism of AICAR transformylase by pH-dependent
      kinetics, mutagenesis, and quantum chemical calculations.
AB  - The catalytic mechanism of 5-aminoimidazole-4-carboxamide ribonucleotide
      transformylase (AICAR Tfase) is evaluated with pH dependent kinetics, site
      directed mutagenesis, and quantum chemical calculations. The chemistry step,
      represented by the burst rates, was not pH-dependent, which is consistent with
      our proposed mechanism that the 4-carboxamide of AICAR assists proton shuttling.
      Quantum chemical calculations on a model system of 5-amino-4-carboxamide
      imidazole (AICA) and formamide using the B3LYP/6-31G level of theory confirmed
      that the 4-carboxamide participated in the proton-shuttling mechanism. The result
      also indicated that the amide-assisted mechanism is concerted such that the
      proton transfers from the 5-amino group to the formamide are simultaneous with
      nucleophilic attack by the 5-amino group. Because the process does not lead to a
      kinetically stable intermediate, the intramolecular proton transfer from the 5
      amino group through the 4-carboxamide to the formamide proceeds in the same
      transition state. Interestingly, the calculations predicted that protonation of
      the N3 of the imidazole of AICA would reduce the energy barrier significantly.
      However, the pK(a) of the imidazole of AICAR was determined to be 3.23 +/- 0.01
      by NMR titration, and AICAR is likely to bind to the enzyme with its imidazole in
      the free base form. An alternative pathway was suggested by modeling Lys266 to
      have a hydrogen-bonding interaction with the N3 of the imidazole of AICAR. Lys266
      has been implicated in catalysis based on mutagenesis studies and the recent X
      ray structure of AICAR Tfase. The quantum chemical calculations on a model system
      that contains AICA complexed with CH3NH3+ as a mimic of the Lys residue confirmed
      that such an interaction lowered the activation energy of the reaction and
      likewise implicated the 4-carboxamide. To experimentally verify this hypothesis,
      we prepared the K266R mutant and found that its kcat is reduced by 150-fold from
      that of the wild type without changes in substrate and cofactor Km values. The
      kcat-pH profile indicated virtually no pH-dependence in the pH range 6-10.5. The
      results suggest that the ammonium moiety of Lys or Arg is important in catalysis,
      most likely acting as a general acid catalyst with a pK(a) value greater than
      10.5. The H267A mutant was also prepared since His267 has been found in the
      active site and implicated in catalysis. The mutant enzyme showed no detectable
      activity while retaining its binding affinity for substrate, indicating that it
      plays a critical role in catalysis. We propose that His267 interacts with Lys266
      to aid in the precise positioning of the general acid catalyst to the N3 of the
      imidazole of AICAR.

PMID- 11457278
TI  - Kinetic mechanism of acetyl-CoA synthase: steady-state synthesis at variable
      Co/Co2 pressures.
AB  - Steady-state initial rates of acetyl-CoA synthesis (upsilon/[E(tot)]) catalyzed
      by acetyl-CoA synthase from Clostridium thermoaceticum (ACS) were determined at
      various partial pressures of CO and CO2. When [CO] was varied from 0 to 100
      microM in a balance of Ar, rates increased sharply from 0.3 to 100 min(-1). At
      [CO] > 100 microM, rates declined sharply and eventually stabilized at 10 min(-1)
      at 980 microM CO. Equivalent experiments carried out in CO2 revealed similar
      inhibitory behavior and residual activity under saturating [CO]. Plots of
      upsilon/[E(tot)] vs [CO2] at different fixed inhibitory [CO] revealed that
      Vmax/[E(tot)] (kcat) decreased with increasing [CO]. Plots of upsilon/[E(tot)] vs
      [CO2] at different fixed noninhibitory [CO] showed that Vmax/[E(tot)] was
      insensitive to changes in [CO]. Of eleven candidate mechanisms, the simplest one
      that fit the data best had the following key features: (a) either CO or CO2 (at a
      designated reductant level and pH) activate the enzyme (E' + CO right arrow over
      left arrow E, E' + CO2/2e-/2H+ right arrow over left arrow E); (b) CO and CO2 are
      both substrates that compete for the same enzyme form (E + CO right arrow over
      left arrow ECO, E + CO2/2e-/2H+ right arrow over left arrow ECO, and ECO --> E +
      P); (c) between 3 and 5 molecules of CO bind cooperatively to an enzyme form
      different from that to which CO2 and substrate CO bind (nCO + ECO right arrow
      over left arrow (CO)nECO), and this inhibits catalysis; and (d) the residual
      activity arises from either the (CO)nECO state or a heterogeneous form of the
      enzyme. Implications of these results, focusing on the roles of CO and CO2 in
      catalysis, are discussed.

PMID- 11457279
TI  - Nonplanar aromatic compounds. 5. A atrategy for the synthesis of cis-10b,10c
      dimethyl-10b,10c-dihydropyrenes. First crystal structure of a cis-10b,10c
      dimethyl-10b,10c-dihydropyrene.
AB  - Through the use of a potentially removable tether, a heavily substituted 10b,10c
      dimethyl-10b,10c-dihydropyrene (DMDHP), 20, was synthesized exclusively as the
      cis-isomer. It exists as the major component (20:1) in an equilibrium with its
      valence isomer syn-[2.2]metacyclophanediene 19. An X-ray crystal structure
      determination of 20, a cis-(2,7)-10b,10c-dihydropyrenophane, provided the first
      experimental measurements of the cis-DMDHP skeleton. The observed bond
      alternation in the [14]annulene was found to be larger than that of the
      corresponding trans-DMDHP framework. Prior MMPI calculations, on which previous
      discussion of the structure of the cis-DMDHP system had been based, are in very
      good agreement with the experimental results. Our own DFT calculations predict a
      more symmetric and more bond equalized structure than was observed in 20.

PMID- 11457280
TI  - Tautomeric equilibrium between penta- and hexacoordinate silicon chelates. A
      chloride bridge between two pentacoordinate silicons.
AB  - The reaction of O-trimethylsilyl-1,1-dimethyl-2-trifluoroacetylhydrazine (1a)
      with chloromethyl(methyl)dichlorosilane affords an unexpected equilibrium
      mixture, 10a right arrow over left arrow 11a, between a neutral hexacoordinate
      silicon chelate with a covalent chloro ligand (10a) and an ionic pentacoordinate
      silicon complex (11a). The equilibrium reaction consists formally of a migration
      of the covalent chloro ligand from silicon to an adjacent ammonium nitrogen, as a
      chloride anion, and thus constitutes a novel type of tautomeric reaction.
      Crystallographic and NMR data provide evidence for the reaction. Temperature,
      solvent, substituent, and counterion effects on the tautomeric equilibrium are
      discussed: when the temperature of the mixture is raised, the equilibrium ratio
      10a/11a increases. Formation of the mixture in toluene, a nonionizing solvent,
      shifts the equilibrium completely toward the neutral 10a. When the initial
      hydrazide has a phenyl (11c) or a hydrogen (11b) group as substituent, rather
      than CF3, the equilibrium is shifted to the ionic side. Replacement of the
      chloride counterion by triflate, using trimethylsilyl triflate, shifts the
      10a/11a mixture to the ionic side. Low-temperature NMR monitoring of the stepwise
      formation of 10/11 was carried out and provided insight into the reaction
      mechanism. In an attempt to grow crystals of 11c, the pentacoordinate tautomer
      analogue, an unprecedented chloride-bridged disiloxane complex, with two
      pentacoordinate silicons sharing a common axial chloro ligand, crystallized and
      was characterized and described.

PMID- 11457281
TI  - A novel approach for the formation of carbon-nitrogen bonds: azidation of alkyl
      radicals with sulfonyl azides.
AB  - Two preparatively attractive methods for the azidation of alkyl radicals are
      described. Secondary and tertiary alkyl iodides and dithiocarbonates are easily
      converted into the corresponding azides, either by reaction with ethanesulfonyl
      azide in the presence of dilauroyl peroxide, or by treatment with benzenesulfonyl
      azide and hexabutylditin in the presence of a radical initiator. Interestingly,
      intramolecular tandem radical cyclization-azidation processes can be performed in
      high yields.

PMID- 11457282
TI  - Insertion of H2C=CHX (X = F, Cl, Br, O(i)Pr) into (tBu3SiO)3TaH2 and beta-X
      Elimination from (tBu3SiO)3HTaCH2CH2X (X = OR): relevance to Ziegler-Natta
      copolymerizations.
AB  - The insertion of H2C=CHX (X = OR; R = Me, Et, nPr, (i)Pr, CH=CH2, Ph) into
      (tBu3SiO)3TaH2 (1) afforded (tBu3SiO)3HTaCH2CH2X (2-CH2CH2X), which beta-X
      eliminated to give ethylene and (tBu3SiO)3HTaX (3-X). beta-X-elimination rates
      were inversely proportional to the size of R. An X-ray crystallographic study of
      (tBu3SiO)3HTaCH2CH2O(t)Bu (2-CH2CH2O(t)Bu) revealed a distorted trigonal
      bipyramidal structure with an equatorial plane containing the hydride and a 
      CH2CH2O(t)Bu ligand with a staggered disposition. erythro- and threo
      (tBu3SiO)3HTaCHDCHDOEt (2-CHDCHDOEt) are staggered in solution, according to (1)H
      NMR spectroscopic studies, and eliminated cis- and trans-HDC=CHD, respectively,
      helping verify the four-centered transition state for beta-OEt-elimination. When
      X = F, Cl, or Br, 2-CH2CH2X was not observed en route to 3-X, signifying that
      olefin insertion was rate-determining. Insertion rates suggested that substantial
      positive charge on the substituted carbon was incurred. The reactivity of other
      H2C=CHX with 1, and a discussion of the observations and their ramifications on
      the incorporation of functionalized monomers in Ziegler-Natta copolymerizations,
      are presented.

PMID- 11457283
TI  - Solitaire and gemini metallocene porphyrazines.
AB  - We report the synthesis and physical characterization of a series of peripherally
      functionalized porphyrazines (pzs) of the forms H2[pz(A;B3)] and trans
      H2[pz(A2);B2], where A is a dithiolene chelate of molybdocene or vanadocene and B
      is a solublizing group. The precursor pz's 8 and 9, of the form H2[pz(A;B3)],
      where A = (4-(butyloxycarbonyl)-S-benzyl)2 and B = di-tert-butylphenyl (8) or di
      n-propyl (9), have been prepared, deprotected, and peripherally metalated with
      molybdocene and vanadocene to form 1(Mo(IV)) and 1(V(IV)), prepared from 8, and
      2(Mo(IV)) from 9, respectively. Likewise, the protected trans-H2[pz(A2);B2)],
      where A = (S-benzyl)2 and B = 3,6-butyloxybenzene (12) or A = (S-benzyl)2 and B =
      (tert-butylphenyl)2 (13), have been prepared and peripherally metalated with
      molybdocene and vanadocene to give the trans dinuclear complexes,
      3(Mo(IV),Mo(IV)), 3(V(IV),V(IV)) (from 12), and 4(V(IV),V(IV)) (from 13). A
      crystal structure of the trans vanadocene pz 4(V(IV),V(IV)) is presented; the
      distance between the two vanadium atoms is 14.5 A. The molybdocene-appended pz's
      are highly redox active and exhibit cyclic voltammograms that are more than just
      the sum of the metallocene and the parent pz's. Chemical oxidation with FcPF6
      gives the Mo(V) species 1(Mo(V)), 2(Mo(V)), 3(Mo(V),Mo(IV)), and 3(Mo(V),Mo(V)).
      Their EPR spectra are indicative of extensive delocalization from the Mo(V) into
      the dithiolato-pz. The EPR spectrum of the mononuclear paramagnetic vanadocene
      pz, 1(V(IV)), shows an expected 8-line pattern for an S = 2 system with hyperfine
      coupling to a single 51V (I = 7/2) nucleus, but the dinuclear vanadocene pz's,
      3(V(IV),V(IV)) and 4(V(IV),V(IV)), exhibit a striking 15-line pattern of the same
      breadth from the S = 1 state formed by exchange coupling between the S = 2
      vanadium centers of a dinuclear complex. Thus, the porphyrazine macrocycle is
      capable of mediating magnetic exchange interactions between metal ions bound to
      the periphery, separated by 14.5 A.

PMID- 11457284
TI  - Supramolecular origins of product selectivity for methanol-to-olefin catalysis on
      HSAPO-34.
AB  - Ethylene selectivity in methanol-to-olefin (MTO) catalysis is related to the
      number of methyl groups on benzene rings trapped in the nanocages of the
      preferred catalyst HSAPO-34. By correlating the time evolutions of the catalysts'
      13C NMR spectra and the volatile product distribution following abrupt cessation
      of methanol flow, we discovered that (in the absence of other adsorbates) propene
      is favored by methylbenzenes with four to six methyl groups but ethylene is
      predominant from those with two or three methyl groups. We substantially
      increased ethylene selectivity by operating at lower methanol partial pressures
      or higher temperatures, either of which reduces the steady-state average methyl
      substitution. As a step toward a kinetic analysis of the MTO reaction on HSAPO
      34, we treated each nanocage with a methylbenzene molecule as a supramolecule
      capable of unimolecular dissociation into ethylene or propene and a less highly
      substituted methylbenzene. Addition of a water molecule to a nanocage containing
      a methylbenzene produces a distinct supramolecule with unique properties. Indeed,
      co-feeding water with methanol significantly increased the average number of
      methyl groups per ring at steady state relative to identical conditions without
      additional water, and also increased ethylene selectivity, apparently through
      transition state shape selectivity.

PMID- 11457285
TI  - Cu(x)UTe3: stabilization of UTe3 in the ZrSe3 structure type via copper
      insertion. The artifact of Te-Te chains and evidence for distortions due to long
      range modulations.
AB  - The ternary phase, Cu(x)UTe3 (x = 0.25 and 0.33), was synthesized from a 3/1/4
      mixture of Cu/U/Te that was heated to 800 degrees C for 6 days and cooled at a
      rate of -4 degrees C x h(-1). It adopts the monoclinic space group P2(1)/m with a
      = 6.0838(12) A, b = 4.2140(8) A, c = 10.361(2) A, beta = 98.83(3) degrees, and V
      = 262.47(9) A3 (for x approximately 0.25). The structure is built from UTe3
      layers of ZrSe3-type that are connected in the [001] direction by Cu atoms. The
      Cu atoms stabilize alpha-UTe3 by inserting between the layers. Cu(x)UTe3 can be
      prepared rationally via a soft chemistry route by reaction of Cu with alpha-UTe3.
      The structural analysis suggests the presence of straight chains of Te atoms (
      approximately 3.0 A apart) along the a-axis but this is an artifact as shown by
      electron diffraction studies of Cu(x)UTe3 that indicate the existence of a
      supercell along the a-axis. Pair distribution function analysis (PDF) was used to
      show that the Te-Te chains contain Te-Te dimers at 2.74 A. Charge transport
      measurements suggest a narrow gap semiconductor but they also indicate anomalous
      behavior as a function of temperature with a n-type to p-type transition at
      approximately 40 K.

PMID- 11457286
TI  - Chiral Ansa metallocenes with Cp ring-fused to thiophenes and pyrroles:
      syntheses, crystal structures, and isotactic polypropylene catalysts.
AB  - Syntheses, crystal structures, and polymerization data for new isospecific
      metallocenes (heterocenes) having cyclopentenyl ligands b-fused to substituted
      thiophenes (Tp) and pyrroles (Pyr) are reported. The C2- and C1-symmetric
      heterocenes are dimethylsilyl bridged, have methyl groups adjacent to the
      bridgehead carbon atoms, and have aryl substituents protruding in the front. rac
      Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2/MAO (MAO = methyl alumoxanes) is the most
      active metallocene catalyst for polypropylene reported to date. rac-Me2Si(2,5-Me2
      3-Ph-6-Cp[b]Tp)2ZrCl2 and rac-Me2Si(2,5-Me2-1-Ph-4-Cp[b]Pyr)2ZrCl2 have the same
      structure, and the former is 6 times more active, produces half the total
      enantiofacial errors, and is 3.5 times less regiospecific in propylene
      polymerizations at the same conditions. rac-Me2Si(2-Me-4-Ph-1-Ind)2ZrCl2/MAO is
      3.5 times lower in activity than rac-Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2
      catalyst, and while the former is the more stereospecific and the less
      regiospecific, the sum of these two enantioface errors is the same for both
      species. Fine-tuning the heterocene sterics by changing selected hydrogen atoms
      on the ligands to methyl groups influenced their catalyst activities,
      stereospecificites, regiospecificites, and isotactic polypropylene (IPP) Mw.
      Thus, both substituting a hydrogen atom adjacent to the phenyl ring with a methyl
      group on an azapentalenyl ligand system and replacing one and then two hydrogens
      on the phenyl ring with methyls on thiopentalenyl ligands provided increased
      polymer Tm and Mw with increasing ligand bulk. Polymer molecular weights are
      sensitive to and inversely proportional to MAO concentration, and the catalyst
      activities increase when hydrogen is added for molecular weight control. The
      polymer Tm values with the thiopentalenyls as TIBAL/[Ph3C][B(C6F5)4] systems were
      higher than with MAO as catalyst activator. A racemic C1, pseudo-meso complex
      with a hybrid dimethylsilyl-bridged 2-Me-4-Ph-1-Ind/2,5-Me2-4-Ph-1-Cp[b]Pyr
      ligand produced the first sample of IPP with all the steric pentad intensities
      fitting the enantiomorphic site control model. Speculative mechanistic
      considerations are offered regarding electronic effects of the heteroatoms and
      steric effects of the ligand structures, the preferred phenyl torsion angles, and
      anion effects.

PMID- 11457287
TI  - Building blocks for molecule-based magnets: a theoretical study of triplet
      singlet gaps in the dianion of rhodizonic acid 1,4-dimethide and its derivatives.
AB  - Reduction of 1,4-dimethylenecyclohexane-2,3,5,6-tetrone forms the title dianion
      1(2-), which may also be formulated as the 1,4-dimethide of deprotonated
      rhodizonic acid. Substituted versions of this species, designed as a charged
      electronic analogue of dimethylenecyclobutadiene, are proposed as building blocks
      for assembly of molecule-based magnets. A possible mode of self-organization of
      their metal salts into 2-D structures with intermolecular ferromagnetic coupling
      is outlined. Full pi space CAS(14,12)/6-31+G//CAS(14,12)/ 6-31G calculations were
      performed to probe the ground spin state (singlet vs triplet) of 1(2-) as a
      function of substituent variations. This study has found that a triplet ground
      state preference as high as 4.5 kcal/mol may be achieved for the symmetrically
      coordinated dianion.

PMID- 11457288
TI  - 2-Deoxy-beta-D-erythro-pentofuranose: hydroxymethyl group conformation and
      substituent effects on molecular structure, ring geometry, and NMR spin-spin
      coupling constants from quantum chemical calculations.
AB  - The effect of hydroxymethyl conformation (gg, gt, and tg rotamers about the C4-C5
      bond) on the conformational energies and structural parameters (bond lengths,
      bond angles, bond torsions) of the 10 envelope forms of the biologically relevant
      aldopentofuranose, 2-deoxy-beta-D-erythro-pentofuranose (2-deoxy-D-ribofuranose)
      2, has been investigated by ab initio molecular orbital calculations at the HF/6
      31G level of theory. C4-C5 bond rotation induces significant changes in the
      conformational energy profile of 2 (2gt and 2tg exhibit one global energy
      minimum, whereas 2gg exhibits two nearly equivalent energy minima), and
      structural changes, especially those in bond lengths, are consistent with
      predictions based on previously reported vicinal, 1,3- and 1,4-oxygen lone pair
      effects. HF/6-31G-optimized envelope geometries of 2gg were re-optimized using
      density functional theory (DFT, B3LYP/6-31G), and the resulting structures were
      used in DFT calculations of NMR spin-spin coupling constants involving 13C (i.e.,
      J(CH) and J(CC) over one, two, and three bonds) in 2gg according to methods
      described previously. The computed J-couplings were compared to those reported
      previously in 2gt to assess the effect of C4-C5 bond rotation on scalar couplings
      within the furanose ring and hydroxymethyl side chain. The results confirm prior
      predictions of correlations between 2J(CH), 3J(CH), 2J(CC) and 3J(CC), and ring
      conformation, and verify the usefulness of a concerted application of these
      couplings (both their magnitudes and signs) in assigning preferred ring and C4-C5
      bond conformations in aldopentofuranosyl rings. The new calculated J-couplings in
      2gg have particular relevance to related J-couplings in DNA (and RNA indirectly),
      where the gg rotamer, rather than the gt rotamer, is observed in most native
      structures. The effects of two additional structural perturbations on 2 were also
      studied, namely, deoxygenation at C5 (yielding 2,5-dideoxy-beta-D-erythro
      pentofuranose 4) and methyl glycosidation at O1 (yielding methyl 2-deoxy-beta-D
      erythro-pentofuranoside 5) at the HF/6-31G level. The conformational energy
      profile of 4 resembles that found for 2gt, not 2gg, indicating that 4 is an
      inappropriate structural mimic of the furanose ring in DNA. Glycosidation failed
      to induce differential stabilization of ring conformations containing an axial C1
      O1 bond (anomeric effect), contrary to experimental data. The latter discrepancy
      indicates that either the magnitude of this differential stabilization depends on
      ring configuration or that solvent effects, which are neglected in these
      calculations, play a role in promoting this stabilization.

PMID- 11457289
TI  - Comparison of aqueous molecular dynamics with NMR relaxation and residual dipolar
      couplings favors internal motion in a mannose oligosaccharide.
AB  - An investigation has been performed to assess how aqueous dynamical simulations
      of flexible molecules can be compared against NMR data. The methodology compares
      state-of-the-art NMR data (residual dipolar coupling, NOESY, and (13)C
      relaxation) to molecular dynamics simulations in water over several nanoseconds.
      In contrast to many previous applications of residual dipolar coupling in
      structure investigations of biomolecules, the approach described here uses
      molecular dynamics simulations to provide a dynamic representation of the
      molecule. A mannose pentasaccharide, alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)
      alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->2)-D-Manp, was chosen as the model
      compound for this study. The presence of alpha-linked mannan is common to many
      glycopeptides, and therefore an understanding of the structure and the dynamics
      of this molecule is of both chemical and biological importance. This paper sets
      out to address the following questions. (1) Are the single structures which have
      been used to interpret residual dipolar couplings a useful representation of this
      molecule? (2) If dynamic flexibility is included in a representation of the
      molecule, can relaxation and residual dipolar coupling data then be
      simultaneously satisfied? (3) Do aqueous molecular dynamics simulations provide a
      reasonable representation of the dynamics present in the molecule and its
      interaction with water? In summary, two aqueous molecular dynamics simulations,
      each of 20 ns, were computed. They were started from two distant conformations
      and both converged to one flexible ensemble. The measured residual dipolar
      couplings were in agreement with predictions made by averaging the whole ensemble
      and from a specific single structure selected from the ensemble. However, the
      inclusion of internal motion was necessary to rationalize the relaxation data.
      Therefore, it is proposed that although residual dipolar couplings can be
      interpreted as a single-structure, this may not be a correct interpretation of
      molecular conformation in light of other experimental data. Second, the
      methodology described here shows that the ensembles from aqueous molecular
      dynamics can be effectively tested against experimental data sets. In the
      simulation, significant conformational motion was observed at each of the
      linkages, and no evidence for intramolecular hydrogen bonds at either alpha(1-
      >2) or alpha(1-->3) linkages was found. This is in contrast to simulations of
      other linkages, such as beta(1-->4), which are often predicted to maintain
      intramolecular hydrogen bonds and are coincidentally predicted to have less
      conformational freedom in solution.

PMID- 11457290
TI  - Ultrahigh field MAS NMR dipolar correlation spectroscopy of the histidine
      residues in light-harvesting complex II from photosynthetic bacteria reveals
      partial internal charge transfer in the B850/His complex.
AB  - Low-temperature 15N and 13C CP/MAS (cross-polarization/magic angle spinning) NMR
      has been used to analyze BChl-histidine interactions and the electronic structure
      of histidine residues in the light-harvesting complex II (LH2) of
      Rhodopseudomonas acidophila. The histidines were selectively labeled at both or
      one of the two nitrogen sites of the imidazole ring. The resonances of histidine
      nitrogens that are interacting with B850 BChl a have been assigned. Specific 15N
      labeling confirmed that it is the tau-nitrogen of histidines which is ligated to
      Mg2+ of B850 BChl molecules (beta-His30, alpha-His31). The pi-nitrogens of these
      Mg2+-bound histidines were found to be protonated and may be involved in hydrogen
      bond interactions. Comparison of the 2-D MAS NMR homonuclear (13C-13C) dipolar
      correlation spectrum of [13C6,15N3]-histidines in the LH2 complex with model
      systems in the solid state reveals two different classes of electronic structures
      from the histidines in the LH2. In terms of the 13C isotropic shifts, one
      corresponds to the neutral form of histidine and the other resembles a positively
      charged histidine species. 15N-13C double-CP/MAS NMR data provide evidence that
      the electronic structure of the histidines in the neutral BChl a/His complexes
      resembles the positive charge character form. While the Mg...15N isotropic shift
      confirms a partial positive charge transfer, its anisotropy is essentially of the
      lone pair type. This provides evidence that the hybridization structure
      corresponding to the neutral form of the imidazole is capable of "buffering" a
      significant amount of positive charge.

PMID- 11457291
TI  - Cross-correlated chemical shift modulation: a signature of slow internal motions
      in proteins.
AB  - A novel NMR experiment allows one to characterize slow motion in macromolecules.
      The method exploits the fact that motions, such as rotation about dihedral
      angles, induce correlated fluctuations of the isotropic chemical shifts of the
      nuclei in the vicinity. The relaxation of two-spin coherences involving C(alpha)
      and Cbeta nuclei in proteins provides information about correlated fluctuations
      of the isotropic chemical shifts of C(alpha) and Cbeta. The difference between
      the relaxation rates of double- and zero-quantum coherences and is shown to be
      affected by cross-correlated chemical shift modulation. In ubiquitin, evidence
      for slow motion is found in loops or near the ends of beta-strands and alpha
      helices.

PMID- 11457292
TI  - Elastic bounded diffusion and electron propagation: dynamics of the wiring of a
      self-assembly of immunoglobulins bearing terminally attached ferrocene
      poly(ethylene glycol) chains according to a spatially controlled organization.
AB  - Molecular monolayers of immunoglobulins bearing terminally attached ferrocene
      poly(ethylene glycol) chains (IgG-PEG-Fc) were self-assembled at an electrode
      surface in a step-by-step manner involving antigen-antibody recognition
      reactions. The total number N of assembled IgG-PEG-Fc monolayers and the number
      of spacers n(i) separating two successive IgG-PEG-Fc monolayers were controlled
      and varied. Electron transport through the protein assembly involves the dynamics
      of the terminally attached PEG chains and isotopic electron exchange between
      ferrocene heads belonging to successive IgG-PEG-Fc monolayers. The model of
      elastic bounded diffusion enabled us to analyze quantitatively the dependence of
      the rate of electron transport on N, n(i), and the rate constant (k(e)) of
      isotopic electron exchange. Wiring of a molecular monolayer of redox enzyme is
      also quantitatively characterized.

PMID- 11457293
TI  - Zero-point vibrational effects on proton shieldings: functional-group
      contributions from ab initio calculations.
AB  - We investigate the effects of zero-point vibrational motion on the nuclear
      magnetic shielding constants of a large number of organic molecules. The
      vibrational corrections include anharmonic contributions from the potential
      energy surface and harmonic contributions from the curvature of the property
      surface. Particular attention is paid to vibrational corrections to hydrogen
      shielding constants where we show that vibrational corrections may be
      substantial, ranging from about +0.50 to -0.70 ppm, and thus demonstrating that
      ignoring these effects may give errors in the chemical shifts by more than 1 ppm
      in certain extreme cases. These effects can therefore not be neglected when
      comparing calculated results with experiment, not even for the chemical shifts.
      However, we also demonstrate that the vibrational corrections to the hydrogen
      shieldings are to a large extent transferable from one molecule to another. We
      have tabulated functional vibrational corrections to the hydrogen shieldings,
      based on results for more than 35 molecules. Unfortunately, no similar
      transferability has been observed for the vibrational corrections to shielding
      constants of other nuclei such as carbon, nitrogen, or oxygen.

PMID- 11457294
TI  - Total synthesis of (+)-phorboxazole A.

PMID- 11457295
TI  - Biosynthesis of the 2H-azepine alkaloid chalciporone.

PMID- 11457296
TI  - Strongly luminescent three-coordinate gold(I) polymers: 1D chain-link fence and
      2D chickenwire structures.

PMID- 11457297
TI  - New metal disulfide nanotubes.

PMID- 11457298
TI  - Isolation and X-ray crystal structure of an unusual biscarbene metal complex and
      its reactivity toward cyclopropanation and allylic C-H insertion of
      unfunctionalized alkenes.

PMID- 11457299
TI  - Basis for the right-handed helical sense of double-stranded DNA: formation of the
      right-handed helix by L-oligonucleotides fixed in low-anti glycosyl conformation.

PMID- 11457300
TI  - Transfer and amplification of chiral molecular information to polysilylene
      aggregates.

PMID- 11457301
TI  - The ruthenium-catalyzed reductive decarboxylation of esters: catalytic reactions
      involving the cleavage of acyl-oxygen bonds of esters.

PMID- 11457302
TI  - Enantioselective total synthesis of shahamin K.

PMID- 11457303
TI  - Decomposition of S-nitrosothiols: unimolecular versus autocatalytic mechanism.

PMID- 11457304
TI  - Efficient photocurrent generation in novel self-assembled multilayers comprised
      of [60]fullerene-cationic homooxacalix[3]arene inclusion complex and anionic
      porphyrin polymer.

PMID- 11457305
TI  - Ti(II)-mediated tandem inter- and intramolecular coupling reaction of unsaturated
      hydrocarbons: one-pot preparation of cyclopentanes and cyclohexanes from readily
      available acyclic starting materials.

PMID- 11457306
TI  - Protein effects on the electronic structure of the [Fe4S4]2+ cluster in
      ferredoxin and HiPIP.

PMID- 11457307
TI  - Synthesis of phosphonamide and thiophosphonamide dipeptides.

PMID- 11457308
TI  - Tryptophan absolute stereochemistry in viral coat proteins from raman optical
      activity.

PMID- 11457309
TI  - Design and synthesis of a novel DNA-DNA interstrand adenine-guanine cross-linking
      agent.

PMID- 11457310
TI  - 20 A Cd4In16S35(14-) supertetrahedral T4 clusters as building units in decorated
      cristobalite frameworks.

PMID- 11457313
TI  - A novel consecutive chain transfer reaction to p-methylstyrene and hydrogen
      during metallocene-mediated olefin polymerization.
AB  - This paper describes the first example of consecutive chain transfer reaction,
      first to p-methylstyrene (or styrene) and then to hydrogen, during metallocene
      catalyzed propylene polymerization by rac-Me(2)Si[2-Me-4-Ph(Ind)](2)ZrCl(2)/MAO
      complex. The PP molecular weight is inversely proportional to the molar ratio of
      [p-methylstyrene]/[propylene] and [styrene]/[propylene] with the chain transfer
      constants of k(tr)/k(p) = 1/6.36 and 1/7.5, respectively. Although hydrogen does
      not influence the polymer molecular weight, it greatly affects the catalyst
      activity. Each PP chain formed contains a terminal p-methylstyrene (or styrene)
      unit. The terminal p-MS unit can be metalated to form a stable polymeric anion
      for living anionic polymerization to prepare new PP diblock copolymers, such as
      PP-b-PS, which are very difficult to prepare by other methods. The overall
      process resembles a transformation reaction from metallocene to living anionic
      polymerization.

PMID- 11457314
TI  - Roles of the proximal heme thiolate ligand in cytochrome p450(cam).
AB  - To examine the roles of the proximal thiolate iron ligand, the C357H mutant of
      P450(cam) (CYP101) was characterized by resonance Raman, UV, circular dichroism,
      and activity measurements. The C357H mutant must be reconstituted with hemin for
      activity to be observed. The reconstituted enzyme is a mixture of high and low
      spin species. Low temperature (10 degrees C), low enzyme concentration (1
      microM), high camphor concentration (1 mM), and 5--50 mM buffer concentrations
      increase the high to low spin ratio, but under no conditions examined was the
      protein more than 60% high spin. The C357H mutant has a poorer K(m) for camphor
      (23 vs 2 microM) and a poorer K(d) for putidaredoxin (50 vs 20 microM) than wild
      type P450(cam). The mutant also exhibits a greatly decreased camphor oxidation
      rate, elevated uncoupling rate, and much greater peroxidase activity. Electron
      transfer from putidaredoxin to the mutant is much slower than to the wild-type
      even though redox potential measurements show that the electron transfer remains
      thermodynamically favored. These experiments confirm that the thiolate ligand
      facilitates the O--O bond cleavage by P450 enzymes and also demonstrate that this
      ligand satisfies important roles in protein folding, substrate binding, and
      electron transfer.

PMID- 11457315
TI  - Stepwise and concerted pathways in photoinduced and thermal electron
      transfer/bond-breaking reactions. experimental illustration of similarities and
      contrasts.
AB  - The electrochemical (cyclic voltammetry) and photoinduced (fluorescence
      quenching, quantum yields) reductive cleavages of four compounds, 4-cyano-alpha
      trifluorotoluene (1), dimethylphenyl sulfonium (2), 4-cyanobenzylmethylphenyl
      sulfonium (3), and 4-cyanobenzyl chloride (4), are investigated and compared in
      terms of concerted vs stepwise mechanisms. Bearing in mind that an increase of
      the thermodynamic driving force shifts the mechanism from concerted to stepwise
      and that the driving force is larger under photochemical than under
      electrochemical conditions, 1 and 2 are typical examples where a stepwise
      mechanism is followed with compatible kinetic characteristics under both regimes.
      4 undergoes a concerted electrochemical reductive cleavage, and the same
      mechanism is followed in the photoinduced reaction with consistent kinetic
      characteristics. The case of 3 is of particular interest, since a trend of
      passing from a concerted to a stepwise mechanism when going from the
      electrochemical to the photochemical conditions indeed appears upon analysis of
      the experimental results. The change of mechanism is, however, not complete
      since, in the photoinduced reaction, there is a balanced competition between the
      two pathways. In the same families of compounds, the unsubstituted
      benzylmethylphenyl sulfonium cations shows such a borderline behavior during the
      electrochemical reaction. In the photoinduced reaction, it is the 4-cyano
      derivative which behaves in a borderline manner, in line with the fact that it
      gives rise more readily to a concerted mechanism than the unsubstituted compound.

PMID- 11457316
TI  - NMR solution structure of an oligonucleotide hairpin with a 2'F-ANA/RNA stem:
      implications for RNase H specificity toward DNA/RNA hybrid duplexes.
AB  - The first structure of a 2'-deoxy-2'-fluoro-D-arabinose nucleic acid (2'F
      ANA)/RNA duplex is presented. We report the structural characterization by NMR
      spectroscopy of a small hybrid hairpin, r(GGAC)d(TTCG)2'F-a(GTCC), containing a
      2'F-ANA/RNA stem and a four-residue DNA loop. Complete (1)H, (13)C, (19)F, and
      (31)P resonance assignments, scalar coupling constants, and NOE constraints were
      obtained from homonuclear and heteronuclear 2D spectra. In the chimeric duplex,
      the RNA strand adopts a classic A-form structure having C3' endo sugar puckers.
      The 2'F-ANA strand is neither A-form nor B-form and contains O4' endo sugar
      puckers. This contrasts strongly with the dynamic sugar conformations previously
      observed in the DNA strands of DNA/RNA hybrid duplexes. Structural parameters for
      the duplex, such as minor groove width, x-displacement, and inclination, were
      intermediate between those of A-form and B-form duplexes and similar to those of
      DNA/RNA duplexes. These results rationalize the enhanced stability of 2'F-ANA/RNA
      duplexes and their ability to elicit RNase H activity. The results are relevant
      for the design of new antisense drugs based on sugar-modified nucleic acids.

PMID- 11457317
TI  - Reactivity of (eta(6)-arene)tricarbonylchromium complexes toward additions of
      anions, cations, and radicals.
AB  - A computational and experimental study of additions of electrophiles,
      nucleophiles, and radicals to tricarbonylchromium-complexed arenes is reported.
      Competition between addition to a complexed arene and addition to a noncomplexed
      arene was tested using 1,1-dideuterio-1-iodo-2-((phenyl)tricarbonylchromium)-2
      phenylethane. Reactions under anionic and cationic conditions give exclusive
      formation of 1,1-dideuterio-1-((phenyl)tricarbonylchromium)-2-phenylethane
      arising from addition to the complexed arene. Radical conditions (SmI(2)) afford
      two isomeric products, reflecting a 2:1 preference for radical addition to the
      noncomplexed arene. In contrast, intermolecular radical addition competition
      experiments employing ketyl radical addition to benzene and
      (benzene)tricarbonylchromium show that addition to the complexed aromatic ring is
      faster than attack on the noncomplexed species by a factor of at least 100,000.
      Density functional theory calculations using the B3LYP method, employing a
      LANL2DZ basis set for geometry optimizations and a DZVP2+ basis set for energy
      calculations, for all three reactive intermediates showed that
      tricarbonylchromium stabilizes all three types of intermediates. The
      computational results for anionic addition agree well with established chemistry
      and provide structural and energetic details as reference points for comparison
      with the other reactive intermediates. Intermolecular radical addition leads to
      exclusive reaction on the complexed arene ring as predicted by the computations.
      The intramolecular radical reaction involves initial addition to the complexed
      arene ring followed by an equilibrium leading to the observed product
      distribution due to a high-energy barrier for homolytic cleavage of an exo bond
      in the intermediate cyclohexadienyl radical complex. Mechanisms are explored for
      electrophilic addition to complexed arenes. The calculations strongly favor a
      pathway in which the cation initially adds to the metal center rather than to the
      arene ring.

PMID- 11457318
TI  - Kinetics and mechanism of the (-)-sparteine-mediated deprotonation of (E)-N-Boc-N
      (p-methoxyphenyl)-3-cyclohexylallylamine.
AB  - The (-)-sparteine-mediated asymmetric lithiation-substitution of (E)-N-Boc-N-(p
      methoxyphenyl)-3-cyclohexylallylamine ((E)-5) to afford gamma-substituted
      enantiomerically enriched products 6 is reported. The solution structure for the
      lithiated intermediate 8.1 in these reactions was determined by heteronuclear NMR
      to be a configurationally stable, alpha-lithio, eta(1)-coordinated monomer. This
      intermediate is proposed to exist as two rotamers that are rapidly equilibrating
      on the NMR time scale; competitive electrophilic substitution of each
      conformation results in the formation of Z or E products. Kinetic measurements of
      the lithiation by in situ infrared spectroscopy provide pseudo-first-order rate
      constants for reactions with a variety of concentrations of amine, (-)-sparteine,
      and n-BuLi. The reaction is first order in amine and zero order in 1:1 base-
      ligand complex. When the concentration of n-BuLi is varied independently of (-)
      sparteine concentration, the reaction rate exhibits an inverse dependence on n
      BuLi concentration. The deuterium isotope effect for the reaction was determined
      to be 86 at -75 degrees C, a result consistent with C--H bond breaking in the
      rate-determining step and indicative of tunneling. A reaction pathway involving a
      prelithiation complex is supported by kinetic simulations.

PMID- 11457319
TI  - Aptamer-based folding fluorescent sensor for cocaine.
AB  - We adapted in two steps a deoxyribonucleotide-based aptamer to signal the
      recognition of cocaine: an instability was engineered in one stem of a three-way
      junction that forms the cocaine-binding pocket and the resulting short stem was
      end labeled with a fluorophore and a quencher. In the absence of cocaine, two
      stems are open, but in its presence they close and the three-way junction forms.
      This major structural change brings fluorophore and quencher together thereby
      signaling the presence and concentration of ligand. The sensor is selective for
      cocaine over its metabolites, can operate in serum, and is useful for the
      screening of cocaine hydrolases.

PMID- 11457320
TI  - DFT study of the effect of sigma-ligands on the structure of ester enolates in
      THF, as models of the active center in the anionic polymerization of methyl
      methacrylate.
AB  - A Density Functional Theory (DFT) study was carried out on structures of the
      lithium ester enolate of methyl isobutyrate (MIB-Li) in THF solution, in the
      presence of TMEDA, dimethoxyethane (DME), crown ether 12-crown-4, and cryptand
      2,1,1, as electron donor ligands (sigma-ligands). Both specific solvation with
      THF and/or ligand molecules and nonspecific solvation by the solvent continuum
      were taken into account. The possibility of ligand-separated ion pair formation
      was analyzed for each of the ligands, including THF alone. In most cases
      peripherally solvated dimers are the most stable species. Only in the presence of
      cryptand-2,1,1 was a ligand-separated triple ion pair, (MIB-Li-MIB)(
      )(THF)(2),Li(2,1,1)(1)(+), shown to be comparable in stability to the THF
      solvated dimer, (MIB-Li)(2)(THF)(4). These results are in agreement with
      experimental NMR data on the structure of MIB-Li in the presence of DME, 12-crown
      4, and cryptand-2,1,1. An upfield shift of the (13)C NMR signal of the alpha
      carbon of MIB-Li observed in the presence of cryptand-2,1,1, originally
      attributed to a ligand-separated monomer, MIB(-),Li(2,1,1)(+), was well
      reproduced by Hartree--Fock calculated NMR shifts for the predicted ligand
      separated triple ion pair.

PMID- 11457321
TI  - Dioxygen binding to deoxyhemocyanin: electronic structure and mechanism of the
      spin-forbidden two-electron reduction of o(2).
AB  - Spectroscopically calibrated DFT is used to investigate the reaction coordinate
      of O(2) binding to Hemocyanin (Hc). A reaction path is calculated in which O(2)
      approaches the binuclear copper site with increasing metal-ligand overlap, which
      switches the coordination mode from end-on eta(1)-eta(1), to mu-eta(1):eta(2),
      then to butterfly, and finally to the planar [Cu(2)(mu-eta(2):eta(2)O(2))]
      structure. Analysis of the electronic structures during O(2) binding reveals that
      simultaneous two-electron transfer (ET) takes place. At early stages of O(2)
      binding the energy difference between the triplet and the singlet state is
      reduced by charge transfer (CT), which delocalizes the unpaired electrons and
      thus lowers the exchange stabilization onto the separated copper centers. The
      electron spins on the copper(II) ions are initially ferromagnetically coupled due
      to close to orthogonal magnetic orbital pathways through the dioxygen bridging
      ligand, and a change in the structure of the Cu(2)O(2) core turns on the
      superexchange coupling between the coppers. This favors the singlet state over
      the triplet state enabling intersystem crossing. Comparison with mononuclear
      model complexes indicates that the protein matrix holds the two copper(I) centers
      in close proximity, which enthalpically and entropically favors O(2) binding due
      to destabilization of the reduced binuclear site. This also allows regulation of
      the enthalpy by the change of the Cu--Cu distance in deoxyHc, which provides an
      explanation for the O(2) binding cooperativity in Hc. These results are compared
      to our earlier studies of Hemerythrin (Hr) and a common theme emerges where the
      spin forbiddeness of O(2) binding is overcome through delocalization of unpaired
      electrons onto the metal centers and the superexchange coupling of the metal
      centers via a ligand bridge.

PMID- 11457322
TI  - Charge-transfer forces in the self-assembly of heteromolecular reactive solids:
      successful design of unique (single-crystal-to-single-crystal) Diels--Alder
      cycloadditions.
AB  - Electron donor/acceptor (EDA) interactions are found to be a versatile
      methodology for the engineering of reactive heteromolecular crystals. In this
      way, a series of the charge-transfer pi-complexes between bis(alkylimino)-1,4
      dithiin acceptors and anthracene donors are shown to form heteromolecular (1:1)
      crystalline solids that spontaneously undergo stereoselective [2 + 4] Diels-
      Alder cycloadditions. The flexible nature of the 1,4-dithiin moiety allows this
      homogeneous topochemical transformation to proceed with minimal distortion of the
      crystal lattice. As a result, a unique (single) crystal phase of the Diels--Alder
      adduct can be produced anti-thermodynamically with a molecular arrangement very
      different from that in solvent-grown crystals. Such a topochemical reaction
      between bis(methylimino)-1,4-dithiin and anthracene proceeds thermally and
      homogeneously up to very high conversions without disintegration of the single
      crystal. This ideal case of the mono-phase topochemical conversion can be
      continuously monitored structurally (X-ray crystallography) and kinetically (NMR
      spectroscopy) throughout the entire range of the crystalline transformation. The
      resultant "artificial" crystal of the Diels--Alder adduct is surprisingly stable
      despite its different symmetry and packing mode compared to the naturally grown
      (thermodynamic) crystal.

PMID- 11457323
TI  - Photoacoustic calorimetry and quantum yields of Mo(CO)(6) ligand exchange in
      linear alkanes: determination of volume of reaction, energetics, and kinetics of
      nucleophile displacement of alkane from Mo(CO)(5)(alkane).
AB  - Photoacoustic calorimetry (PAC) and actinometry studies were used to determine
      the enthalpies and volumes of reaction for the production of a transient
      intermediate, Mo(CO)(5)-alkane, and for its subsequent reaction with
      tetrahydrofuran (THF). Both the enthalpy and the volume of reaction contribute to
      the photoacoustic signal and have been resolved by changing the solvent thermal
      expansion properties with a series of linear alkanes. The enthalpies for
      substitution of CO on Mo(CO)(6) by an alkane and of coordinated alkane on
      Mo(CO)(5)(alkane) by THF are 30 and -14 kcal/mol, respectively. Likewise, the
      volumes of reaction are 18 and -1 mL/mol. From available data for the Mo--CO bond
      energy, these results allow the calculation of the Mo-alkane and Mo-THF bond
      energies (11 and 25 kcal/mol, respectively). The Mo-alkane result is 7 kcal/mol
      less than that from our previous PAC study, which ignored the volume of reaction,
      and is in better agreement with the results of kinetic studies. The large
      absolute difference in the reaction volumes for each step is partially attributed
      to a void volume created during the formation of the Mo--THF bond. In general,
      the volume of reaction cannot be neglected in the calculation of enthalpies of
      ligand substitution from PAC studies. The quantum yields for photosubstitution of
      Mo(CO)(6), in contrast to Cr(CO)(6), were found to be insensitive to the chain
      length of the alkane solvent.

PMID- 11457324
TI  - Substituent-dictated partitioning of intermediates on the sulfide singlet oxygen
      reaction surface. A new mechanism for oxidative C--S bond cleavage in alpha
      hydroperoxy sulfides.
AB  - The reactions of singlet oxygen with 17 sulfides bearing either anion or radical
      stabilizing substituents are reported. The abilities of substituents to modify
      product compositions in both the oxidative cleavage and sulfide oxidation
      pathways are analyzed in terms of partitioning of the hydroperoxy sulfonium ylide
      intermediate. Evidence is presented that suggests that the hydroperoxy sulfonium
      ylide exists in both diradical and zwitterionic forms. In addition, both inter-
      and intramolecular pathways for decomposition of alpha-hydroperoxy sulfides are
      suggested to rationalize the substituent-dependent formation of oxidative C--S
      bond cleavage products.

PMID- 11457325
TI  - Selective lithium ion binding involving inositol-based
      tris(spirotetrahydrofuranyl) ionophores: formation of a rodlike supramolecular
      ionic polymer from a homoditopic dimer.
AB  - The stereoselective replacement of all three hydroxyl groups in myo-inositol
      orthoformate by spirotetrahydrofuran rings in that manner which projects the C--O
      bonds in the molecular interior has been examined. The heterocyclic components
      were introduced sequentially, a protocol that demonstrated the utility of
      precomplexation to LiClO(4) as a stereocontrol tactic. The capability of 3 to
      coordinate to alkali metal ions was quantified. The conformationally restricted
      nature of this ligand conveys high selectivity for binding to lithium ion. Beyond
      that, the ionophore prefers to form 2:1 complexes with Li(+) and exhibits little
      tendency for 1:1 stoichiometry. These properties are shared by the "dimer" 36, in
      which two building blocks of type 3 have been conjoined by a 1,3-butadiyne tether
      positioned at the ortho ester terminus. This bifacial ligand reacts with one
      equivalent of LiClO(4) or LiBF(4) to form rodlike ionic polymers. Alternative
      recourse to lithium picrate results in production of the doubly capped
      homoditopic complex 41. Various other aspects of the chemistry peculiar to these
      systems are discussed.

PMID- 11457326
TI  - Luminescent mu-ethynediyl and mu-butadiynediyl binuclear gold(I) complexes:
      observation of (3)(pi pi*) emissions from bridging C(n)(2-) units.
AB  - The synthesis and X-ray structural and spectroscopic characterization for LAuC
      triple bond CAuL x 4CHCl(3) and LAuC triple bond C--C triple bond CAuL x
      2CH(2)Cl(2) (1 x 4CHCl(3) and 2 x 2CH(2)Cl(2), respectively; L = PCy(3),
      tricyclohexylphosphine) are reported. The bridging C(n)(2-) units are
      structurally characterized as acetylene or diacetylene units, with C triple bond
      C distances of 1.19(1) and 1.199(8) A for 1 x 4CHCl(3) and 2 x 2CH(2)Cl(2),
      respectively. An important consequence of bonding to Au(I) for the C(n)(2-)
      moieties is that the lowest-energy electronic excited states, which are
      essentially acetylenic (3)(pi pi*) in nature, acquire sufficient allowedness via
      Au spin-orbit coupling to appear prominently in both electronic absorption and
      emission spectra. The origin lines for both complexes are well-defined and are
      observed at 331 and 413 nm for 1 and 2, respectively. Sharp vibronic progressions
      corresponding to v(C triple bond C) are observed in both emission and absorption
      spectra. The acetylenic (3)(pi pi) excited state of 2 has a long lifetime (tau(0)
      = 10.8 mus) in dichloromethane at room temperature and is a powerful reductant (E
      degrees [Au(2)(+)/Au(2)] < or = -1.85 V vs SSCE).

PMID- 11457327
TI  - Reactions of an amphoteric terminal tungsten methylidyne complex.
AB  - Treatment of [Tp'(CO)(2)W triple bond C--PPh(3)][PF(6)] (Tp' = hydridotris(3,5
      dimethylpyrazolylborate)) with Na[HBEt(3)] in THF forms the methylidyne complex
      Tp'(CO)(2)W triple bond C--H via formyl and carbene intermediates Tp'(CO)(C(O)H)W
      triple bond C- PPh(3) and Tp'(CO)(2)W=C(PPh(3))(H), respectively. Spectroscopic
      features reported for Tp'(CO)(2)W triple bond C--H include the W triple bond C
      stretch (observed by both IR and Raman spectroscopy) and the (183)W NMR signal
      (detected by a (1)H, (183)W 2D HMQC experiment). Protonation of the Tp'(CO)(2)W
      triple bond C--H methylidyne complex with HBF(4).Et(2)O yields the cationic alpha
      agostic methylidene complex [Tp'(CO)(2)W=CH(2)][BF(4)]. The methylidyne complex
      Tp'(CO)(2)W triple bond C-H can be deprotonated with alkyllithium reagents to
      provide the anionic terminal carbide Tp'(CO)(2)W triple bond C--Li; a downfield
      resonance at 556 ppm in the (13)C NMR spectrum has been assigned to the carbide
      carbon. The terminal carbide Tp'(CO)(2)W triple bond C-Li adds electrophiles at
      the carbide carbon to generate Tp'(CO)(2)W triple bond C--R (R = CH(3), SiMe(3),
      I, C(OH)Ph(2), CH(OH)Ph, and C(O)Ph) Fischer carbynes. A pK(a) of 28.7 was
      determined for Tp'(CO)(2)W triple bond C--H in THF by titrating the terminal
      carbide Tp'(CO)(2)W triple bond C--Li with 2-benzylpyridine and monitoring its
      conversion to Tp'(CO)(2)W triple bond C--H with in situ IR spectroscopy. Addition
      of excess Na[HBEt(3)] to neutral Tp'(CO)(2)W triple bond C--H generates the
      anionic methylidene complex [Na][Tp'(CO)(2)W=CH(2)]. The synthetic methodology
      for generating an anionic methylidene complex by hydride addition to neutral
      Tp'(CO)(2)W triple bond C--H contrasts with routes that utilize alpha-hydrogen
      abstraction or hydride removal from neutral methyl precursors to generate
      methylidene complexes. Addition of PhSSPh to the anionic methylidene complex in
      solution generates the saturated tungsten product Tp'(CO)(2)W(eta(2)-CH(2)SPh) by
      net addition of the SPh(+) moiety.

PMID- 11457328
TI  - Atomic carbon as a terminal ligand: studies of a carbidomolybdenum anion
      featuring solid-state (13)C NMR data and proton-transfer self-exchange kinetics.
AB  - Anion [CMo(N[R]Ar)(3)](-) (R = C(CD(3))(2)CH(3) or (t)Bu, Ar = 3,5-C(6)H(3)Me(2))
      containing one-coordinate carbon as a terminal substituent and related molecules
      have been studied by single-crystal X-ray crystallography, solution and solid
      state (13)C NMR spectroscopy, and density functional theory (DFT) calculations.
      Chemical reactivity patterns for [CMo(N[R]Ar)(3)](-) have been investigated,
      including the kinetics of proton-transfer self-exchange involving
      HCMo(N[R]Ar)(3), the carbidomolybdenum anion's conjugate acid. While the Mo
      triple bond C bond lengths in [K(benzo-15-crown-5)(2)][CMo(N[R]Ar)(3)] and the
      parent methylidyne, HCMo(N[R]Ar)(3), are statistically identical, the carbide
      chemical shift of delta 501 ppm is much larger than the delta 282 ppm shift for
      the methylidyne. Solid-state (13)C NMR studies show the carbide to have a much
      larger chemical shift anisotropy (CSA, 806 ppm) and smaller (95)Mo--(13)C
      coupling constant (60 Hz) than the methylidyne (CSA = 447 ppm, (1)J(MoC) = 130
      Hz). DFT calculations on model compounds indicate also that there is an
      increasing MoC overlap population on going from the methylidyne to the terminal
      carbide. The pK(a) of methylidyne HCMo(N[R]Ar)(3) is approximately 30 in THF
      solution. Methylidyne HCMo(N[R]Ar)(3) and carbide [CMo(N[R]Ar)(3)](-) undergo
      extremely rapid proton-transfer self-exchange reactions in THF, with k = 7 x
      10(6) M(-1) s(-1). Besides being a strong reducing agent, carbide
      [CMo(N[R]Ar)(3)](-) reacts as a nucleophile with elemental chalcogens to form
      carbon-chalcogen bonds and likewise reacts with PCl(3) to furnish a carbon
      phosphorus bond.

PMID- 11457329
TI  - Mesoporous aluminosilicates with ordered hexagonal structure, strong acidity, and
      extraordinary hydrothermal stability at high temperatures.
AB  - Highly ordered hexagonal mesoporous aluminosilicates (MAS-5) with uniform pore
      sizes have been successfully synthesized from assembly of preformed
      aluminosilcate precursors with cetyltrimethylammonium bromide (CTAB) surfactant.
      The aluminosilicate precursors were obtained by heating, at 100--140 degrees C
      for 2--10 h, aluminasilica gels at the Al(2)O(3)/SiO(2)/TEAOH/H(2)O molar ratios
      of 1.0/7.0--350/10.0--33.0/500--2000. Mesoporous MAS-5 shows extraordinary
      stability both in boiling water (over 300 h) and in steam (800 degrees C for 2
      h). Temperature-programmed desorption of ammonia shows that the acidic strength
      of MAS-5 is much higher than that of MCM-41 and is comparable to that of
      microporous Beta zeolite. In catalytic cracking of 1,3,5-triisopropylbenzene and
      alkylation of isobutane with butene, MAS-5 exhibits greater catalytic activity
      and selectivity, as compared with MCM-41 and HZSM-5. The MAS-5 samples were
      characterized with infrared, UV--Raman, and NMR spectroscopy and numerous other
      techniques. The results suggest that MAS-5 consists of both mesopores and
      micropores and that the pore walls of MAS-5 contain primary and secondary
      structural building units, similar to those of microporous zeolites. Such unique
      structural features might be responsible for the observed strong acidity and high
      thermal stability of the mesoporous aluminosilicates with well-ordered hexagonal
      symmetry.

PMID- 11457330
TI  - Resonance Raman studies of the iron(II)--alpha-keto acid chromophore in model and
      enzyme complexes.
AB  - The bidentate coordination of an alpha-keto acid to an iron(II) center via the
      keto group and the carboxylate gives rise to metal-to-ligand charge-transfer
      transitions between 400 and 600 nm in model complexes and in alpha-ketoglutarate
      dependent dioxygenases. Excitation into these absorption bands of the
      Fe(II)TauD(alpha-KG) complex (TauD = taurine/alpha-ketoglutarate dioxygenase,
      alpha-KG = alpha-ketoglutarate) elicits two resonance Raman features at 460 and
      1686 cm(-1), both of which are sensitive to (18)O labeling. Corresponding studies
      of model complexes, the six-coordinate [Fe(II)(6-Me(3)-TPA)(alpha-keto acid)](+)
      and the five-coordinate [Fe(II)(Tp(Ph2))(alpha-keto acid)] (6-Me(3)-TPA = tris[(6
      methyl-2-pyridyl)methyl]amine, Tp(Ph2) = hydrotris(3,5-diphenylpyrazol-1
      yl)borate), lead to the assignment of these two features to the Fe(II)(alpha-keto
      acid) chelate mode and the nu(C==O) of the keto carbonyl group, respectively.
      Furthermore, the chelate mode is sensitive to the coordination number of the
      metal center; binding of a sixth ligand to the five-coordinate
      [Fe(II)(Tp(Ph2))(benzoylformate)] elicits a 9--20 cm(-1) downshift. Thus, the 10
      cm(-1) upshift of the chelate mode observed for Fe(II)TauD(alpha-KG) upon the
      addition of the substrate, taurine, is associated with the conversion of the six
      coordinate metal center to a five-coordinate center, as observed for the iron
      center of clavaminate synthase from X-ray crystallography (Zhang, Z.; et al. Nat.
      Struct. Biol. 2000, 7, 127-133) and MCD studies (Zhou, J.; et al. J. Am. Chem.
      Soc. 1998, 120, 13539--13540). These studies provide useful insights into the
      initial steps of the oxygen activation mechanism of alpha-ketoglutarate-dependent
      dioxygenases.

PMID- 11457331
TI  - Extradiol oxidative cleavage of catechols by ferrous and ferric complexes of
      1,4,7-triazacyclononane: insight into the mechanism of the extradiol catechol
      dioxygenases.
AB  - The major oxygenation product of catechol by dioxygen in the presence of FeCl(2)
      or FeCl(3), 1,4,7-triazacyclononane (TACN), and pyridine in methanol is the
      extradiol cleavage product 2-hydroxymuconic semi-aldehyde methyl ester (Lin, G.;
      Reid, G.; Bugg, T. D. H. J. Chem. Soc. Chem. Commun. 2000, 1119--1120). Under
      these conditions, extradiol cleavage of a range of 3- and 4-substituted catechols
      with electron-donating substituents is observed. The reaction shows a preference
      in selectivity and rate for iron(II) rather than iron(III) for the extradiol
      cleavage, which parallels the selectivity of the extradiol dioxygenase family.
      The reaction also shows a high selectivity for the macrocyclic ligand, TACN, over
      a range of other nitrogen- and oxygen-containing macrocycles. Reaction of
      anaerobically prepared iron-TACN complexes with dioxygen gave the same product as
      monitored by UV/vis spectroscopy. KO(2) is able to oxidize catechols with both
      electron-donating and electron-withdrawing substituents, implying a different
      mechanism for extradiol cleavage. Saturation kinetics were observed for
      catechols, which fit the Michaelis--Menten equation to give k(cat)(app) = 4.8 x
      10(-3) s(-1) for 3-(2',3'-dihydroxyphenyl)propionic acid. The reaction was also
      found to proceed using monosodium catecholate in the absence of pyridine, but
      with different product ratios, giving insight into the acid/base chemistry of
      extradiol cleavage. In particular, extradiol cleavage in the presence of iron(II)
      shows a requirement for a proton donor, implying a role for an acidic group in
      the extradiol dioxygenase active site.

PMID- 11457332
TI  - The ferrocene--lithium cation complex in the gas phase.
AB  - The stable isomers of the ferrocene--lithium cation gas-phase ion complex have
      been studied with the hybrid density functional theory. The method of calculation
      chosen has been tested checking its performance for the more studied protonated
      ferrocene species. Our calculations demonstrate that the procedure used is
      reliable. We have found two isomers of the ferrocene--lithium cation complex
      separated by a barrier of 25.6 kcal/mol. The most stable isomer of this complex
      has Li(+) on-top of one of the cyclopentadienyls, while in the least stable
      isomer Li(+) binds the central iron metal. The latter isomer has been
      characterized as a planetary system in the sense that Li(+) has one thermally
      accessible planar orbit around the central ferrocene moiety. Our calculations
      lead to a value of ferrocene's gas-phase lithium cation basicity of 37.4 kcal/mol
      for the on-top complex and 29.4 kcal/mol for the metal-bound complex.

PMID- 11457333
TI  - Complex of B-DNA with polyamides freezes DNA backbone flexibility.
AB  - The development of sequence-specific minor groove binding ligands is a modern and
      rapidly growing field of research because of their extraordinary importance as
      transcription-controlling drugs. We performed three molecular dynamics
      simulations in order to clarify the influence of minor groove binding of two
      ImHpPyPy-beta-Dp polyamides to the d(CCAGTACTGG)(2) decamer in the B-form. This
      decamer contains the recognition sequence for the trp repressor (5'-GTACT-3'),
      and it was investigated recently by X-ray crystallography. On one hand we are
      able to reproduce X-ray-determined DNA--drug contacts, and on the other hand we
      provide new contact information which is important for the development of
      potential ligands. The new insights show how the beta-tail of the polyamide
      ligands contributes to binding. Our simulations also indicate that complexation
      freezes the DNA backbone in a specific B(I) or B(II) substate conformation and
      thus optimizes nonbonded contacts. The existence of this distinct B(I)/B(II)
      substate pattern also allows the formation of water-mediated contacts. Thus, we
      suggest the B(I) <==> B(II) substate behavior to be an important part of the
      indirect readout of DNA.

PMID- 11457335
TI  - A hydrogen storage mechanism in single-walled carbon nanotubes.
AB  - We have carried out systematic calculations for hydrogen-adsorption and -storage
      mechanism in carbon nanotubes at zero temperature. Hydrogen atoms first adsorb on
      the tube wall in an arch-type and zigzag-type up to a coverage of theta = 1.0 and
      are stored in the capillary as a form of H(2) molecule at higher coverages.
      Hydrogen atoms can be stored dominantly through the tube wall by breaking the C-
      C midbond, while preserving the wall stability of a nanotube after complete
      hydrogen insertion, rather than by the capillarity effect through the ends of
      nanotubes. In the hydrogen-extraction processes, H(2) molecule in the capillary
      of nanotubes first dissociates and adsorbs onto the inner wall and is further
      extracted to the outer wall by the flip-out mechanism. Our calculations describe
      suitably an electrochemical storage process of hydrogen, which is applicable for
      the secondary hydrogen battery.

PMID- 11457334
TI  - Multifrequency high-field EPR study of the tryptophanyl and tyrosyl radical
      intermediates in wild-type and the W191G mutant of cytochrome c peroxidase.
AB  - Multifrequency (95, 190, and 285 GHz) high-field electron paramagnetic resonance
      (EPR) spectroscopy has been used to characterize radical intermediates in wild
      type and Trp191Gly mutant cytochrome c peroxidase (CcP). The high-field EPR
      spectra of the exchange-coupled oxoferryl--trytophanyl radical pair that
      constitutes the CcP compound I intermediate [(Fe(IV)=O) Trp*(+)] were analyzed
      using a spin Hamiltonian that incorporated a general anisotropic spin-spin
      interaction term. Perturbation expressions of this Hamiltonian were derived, and
      their limitations under high-field conditions are discussed. Using numerical
      solutions of the completely anisotropic Hamiltonian, its was possible to simulate
      accurately the experimental data from 9 to 285 GHz using a single set of spin
      parameters. The results are also consistent with previous 9 GHz single-crystal
      studies. The inherent superior resolution of high-field EPR spectroscopy
      permitted the unequivocal detection of a transient tyrosyl radical that was
      formed 60 s after the addition of 1 equiv of hydrogen peroxide to the wild-type
      CcP at 0 degrees C and disappeared after 1 h. High-field EPR was also used to
      characterize the radical intermediate that was generated by hydrogen peroxide
      addition to the W191G CcP mutant. The g- values of this radical (g(x)= 2.00660,
      g(y) = 2.00425, and g(z)= 2.00208), as well as the wild-type transient tyrosyl
      radical, are essentially identical to those obtained from the high-field EPR
      spectra of the tyrosyl radical generated by gamma-irradiation of crystals of
      tyrosine hydrochloride (g(x)= 2.00658, g(y) = 2.00404, and g(z) = 2.00208). The
      low g(x)-value indicated that all three of the tyrosyl radicals were in
      electropositive environments. The broadening of the g(x) portion of the HF-EPR
      spectrum further indicated that the electrostatic environment was distributed. On
      the basis of these observations, possible sites for the tyrosyl radical(s) are
      discussed.

PMID- 11457336
TI  - Rearrangements involving the phenonium ion: a theoretical investigation.
AB  - Rearrangements involving the phenonium ion were investigated by means of a
      B3LYP/6-311G(d,p) study in which the effect of solvent has been incorporated by
      using a PCM solvation model. A rationalization of the whole set of experimental
      facts reported both in the gas phase and in solution was possible thanks to the
      characterization of protonated benzocyclobutene as a minimum energy structure
      and, particularly, to the important preferential stabilization in solution of the
      TS for the isomerization of the phenonium ion to the alpha-methylbenzyl ion,
      which reduces the Gibbs energy barrier of 26.6 kcal/mol for this process in the
      gas phase to a more accessible one of 18.7 kcal/mol in solution.

PMID- 11457337
TI  - Statics and dynamics of ethane molecules in AlPO(4)-5: a molecular dynamics
      simulation study.
AB  - From an experimental perspective, there has been disagreement among researchers
      on whether ethane would display single-file or normal diffusive behavior in the
      channels of AlPO(4)-5. Pulsed field gradient nuclear magnetic resonance
      measurements implied single-file diffusion, while quasielastic neutron scattering
      showed normal diffusion. In this paper we present the results of extensive
      classical molecular dynamics simulations of the diffusion of ethane molecules
      adsorbed in AlPO(4)-5. Our aim is to provide microscopic details of the static
      and dynamic properties of the adsorbed molecules in order to verify whether the
      conditions for the single-file regime can be achieved in a nondefective AlPO(4)-5
      crystal structure.

PMID- 11457338
TI  - Electron transport through thin organic films in metal--insulator--metal
      junctions based on self-assembled monolayers.
AB  - This paper describes an experimentally simple system for measuring rates of
      electron transport across organic thin films having a range of molecular
      structures. The system uses a metal--insulator--metal junction based on self
      assembled monolayers (SAMs); it is particularly easy to assemble. The junction
      consists of a SAM supported on a silver film (Ag-SAM(1)) in contact with a second
      SAM supported on the surface of a drop of mercury (Hg-SAM(2))--that is, a Ag
      SAM(1)SAM(2)-Hg junction. SAM(1) and SAM(2) can be derived from the same or
      different thiols. The current that flowed across junctions with SAMs of aliphatic
      thiols or aromatic thiols on Ag and a SAM of hexadecane thiol on Hg depended both
      on the molecular structure and on the thickness of the SAM on Ag: the current
      density at a bias of 0.5 V ranged from 2 x 10(-10) A/cm(2) for HS(CH(2))(15)CH(3)
      on Ag to 1 x 10(-6) A/cm(2) for HS(CH(2))(7)CH(3) on Ag, and from 3 x 10(-6)
      A/cm(2) for HS(Ph)(3)H (Ph = 1,4-C(6)H(4)) on Ag to 7 x 10(-4) A/cm(2) for HSPhH
      on Ag. The current density increased roughly linearly with the area of contact
      between SAM(1) and SAM(2), and it was not different between Ag films that were
      100 or 200 nm thick. The current--voltage curves were symmetrical around V = 0.
      The current density decreased with increasing distance between the electrodes
      according to the relation I = I(0)e(-beta d(Ag,Hg)), where d(Ag,Hg) is the
      distance between the electrodes, and beta is the structure-dependent attenuation
      factor for the molecules making up SAM(1). At an applied potential of 0.5 V, beta
      was 0.87 +/- 0.1 A(-1) for alkanethiols, 0.61 +/- 0.1 A(-1) for oligophenylene
      thiols, and 0.67 +/- 0.1 A(-1) for benzylic derivatives of oligophenylene thiols.
      The values of beta did not depend significantly on applied potential over the
      range of 0.1 to 1 V. These junctions provide a test bed with which to screen the
      intrinsic electrical properties of SAMs made up of molecules with different
      structures; information obtained using these junctions will be useful in
      correlating molecular structure and rates of electron transport.

PMID- 11457339
TI  - The prediction, morphology, and mechanical properties of the polymorphs of
      paracetamol.
AB  - The analgesic drug paracetamol (acetaminophen) has two reported metastable
      polymorphs, one with better tableting properties than the stable form, and
      another which remains uncharacterized. We have therefore performed a systematic
      crystal structure prediction search for minima in the lattice energy of
      crystalline paracetamol. The stable monoclinic form is found as the global
      lattice-energy minimum, but there are at least a dozen energetically feasible
      structures found, including the well-characterized metastable orthorhombic phase.
      Hence, we require additional criteria to reduce the number of hypothetical
      crystal structures that can be considered as potential polymorphs. For this
      purpose the elastic properties and vapor growth morphology of the known and
      predicted structures have been estimated using second-derivative analysis and the
      attachment-energy model. These inexpensive calculations give reasonable agreement
      with the available experimental data for the known polymorphs. Some of the
      hypothetical structures are predicted to have a low growth rate and plate-like
      morphology, and so are unlikely to be observed. Another is only marginally
      mechanically stable. Thus, this first consideration of such properties in a
      crystal-structure prediction study appears to reduce the number of predicted
      polymorphs while leaving a few candidates for the uncharacterized form.

PMID- 11457340
TI  - Catalyst-based control of [2,3]- and [3,3]-rearrangement in alpha-diazoketone
      derived propargyloxy enols.

PMID- 11457341
TI  - (14)N MAS NMR spectroscopy: the nitrate ion.

PMID- 11457342
TI  - Benzene C-H activation at a charge neutral zwitterionic platinum(II) complex.

PMID- 11457343
TI  - Derivatives of methyl 5-methyl-4-oxo-1,2,4,5,8,8a- hexahydrocyclopropa[c]
      pyrrolo[3,2-e]indole-7-carboxylate: a case of inverse electronic effects on the
      reactivity of CC-1065 derivatives.

PMID- 11457344
TI  - beta-Destabilizing effect of silicon in regioselective hydroxymethylation of beta
      silylcycloalkanone enol acetates by electrochemical method.

PMID- 11457345
TI  - Metallophilicity: the dimerization of bis[(triphenylphosphine)gold(I)]chloronium
      cations.

PMID- 11457346
TI  - A prototype of transition-metal-catalyzed carbothiolation of alkynes.

PMID- 11457347
TI  - Zirconium-mediated synthesis of a new class of 1,4-bis(diphenylphosphino)-1,3
      butadiene-bridged diphosphine, NUPHOS: highly efficient catalysts for palladium
      mediated cross couplings.

PMID- 11457348
TI  - Diastereoselective cobalt-catalyzed aldol and Michael cycloreductions.

PMID- 11457349
TI  - Synthesis and evaluation of bishydroquinone derivatives of (-)-saframycin A:
      identification of a versatile molecular template imparting potent
      antiproliferative activity.

PMID- 11457350
TI  - Noeuromycin, a glycosyl cation mimic that strongly inhibits glycosidases.

PMID- 11457351
TI  - In vivo NMR at 800 MHz to monitor alkaloid metabolism in plant cell cultures
      without tracer labeling.

PMID- 11457352
TI  - Catalytic dehydrogenative coupling of secondary silanes using Wilkinson's
      catalyst.

PMID- 11457353
TI  - Three-component aldimine addition--cyclopropanation. an efficient new methodology
      for amino cyclopropane synthesis.

PMID- 11457354
TI  - Is the linkage region of sphingolipids responsible for lipid raft formation?

PMID- 11457355
TI  - Alternative reactivity of an alpha-ketoglutarate-dependent iron(II) oxygenase:
      enzyme self-hydroxylation.

PMID- 11457356
TI  - Stereochemistry of the core structure of the mycolactones.

PMID- 11457357
TI  - Synthesis of enantioenriched axially chiral anilides from atropisomerically
      enriched tartarate ortho-anilides.

PMID- 11457358
TI  - Enantioselectivity in the reactions of chiral alpha-(N-carbamoyl)alkylcuprates.

PMID- 11457359
TI  - A new catalyst for highly syndiospecific living olefin polymerization:
      homopolymers and block copolymers from ethylene and propylene.

PMID- 11457360
TI  - Time-resolved step-scan fourier transform infrared spectroscopy of alkyl
      phenylglyoxylates.

PMID- 11457361
TI  - N-confused expanded porphyrin: first example of a modified sapphyrin with an
      inverted N-confused pyrrole ring.

PMID- 11457362
TI  - Selenocysteine in native chemical ligation and expressed protein ligation.

PMID- 11457364
TI  - Iterative approach to polycyclic ethers based on stereoselective oxonium ylide
      [2,3]-shifts.

PMID- 11457363
TI  - Myoglobin catalyzes its own nitration.

PMID- 11457365
TI  - Fabrication of novel mesocellular carbon foams with uniform ultralarge mesopores.

PMID- 11457366
TI  - First phenylenevinylene based organogels: self-assembled nanostructures via
      cooperative hydrogen bonding and pi-stacking.

PMID- 11457367
TI  - Controlled synthesis of multi-armed CdS nanorod architectures using
      monosurfactant system.

PMID- 11457368
TI  - New approach to bicyclo [5.3.0] ring systems.

PMID- 11457369
TI  - Cloning and functional expression of cDNA encoding aphidicolan-16 beta-ol
      synthase: a key enzyme responsible for formation of an unusual diterpene skeleton
      in biosynthesis of aphidicolin.

PMID- 11457370
TI  - Infrared and EPR spectroscopic observation of novel open-shell species: the
      fluoroiminomethyl radical (FC*==NH) in solid argon.

PMID- 11457371
TI  - Sequence-specific DNA interstrand cross-linking by imidazole--pyrrole CPI
      conjugate.

PMID- 11457372
TI  - Derivatives of 8-hydroxy-2-methylquinoline are powerful prototypes for zinc
      sensors in biological systems.

PMID- 11457373
TI  - De novo design of a monomeric helical beta-peptide stabilized by electrostatic
      interactions.

PMID- 11457374
TI  - Two-color labeling of oligonucleotide arrays via size-selective scattering of
      nanoparticle probes.

PMID- 11457377
TI  - Metallobleomycin-mediated cleavage of DNA not involving a threading-intercalation
      mechanism.
AB  - The DNA cleavage properties of metallobleomycins conjugated to three solid
      supports were investigated using plasmid DNA, relaxed covalently closed circular
      DNA, and linear duplex DNA as substrates. Cleavage of pBR322 and pSP64 plasmid
      DNAs by Fe(II).BLM A(5)-CPG-C(2) was observed with efficiencies not dissimilar to
      that obtained using free Fe(II).BLM A(5). Similar results were observed following
      Fe(II).BLM A(5)-CPG-C(2)-mediated cleavage of a relaxed plasmid, a substrate that
      lacks ends or negative supercoiling capable of facilitating strand separation.
      BLMs covalently tethered to solid supports, including Fe(II).BLM A(5)-Sepharose
      4B, Fe(II).BLM A(5)-CPG-C(6), and Fe(II).BLM A(5)-CPG-C(2), cleaved a 5'-(32)P
      end labeled linear DNA duplex with a sequence selectivity identical to that of
      free Fe(II).BLM A(5); cleavage predominated at 5'-G(82)T(83)-3' and 5'-G(84)T(85)
      3'. To verify that these results could also be obtained using other
      metallobleomycins, supercoiled plasmid DNA and a linear DNA duplex were employed
      as substrates for Co(III).BLM A(5)-CPG-C(2). Free green Co(III).BLM A(5) was only
      about 2-fold more efficient than green Co(III).BLM A(5)-CPG-C(2) in effecting DNA
      cleavage. A similar result was obtained using Cu(II).BLM A(5)-CPG-C(2) +
      dithiothreitol. In addition, the conjugated Co.BLM A(5) and Cu.BLM A(5) cleaved
      the linear duplex DNA with a sequence selectivity identical to that of the
      respective free metalloBLMs. Interestingly, when supercoiled plasmid DNA was used
      as a substrate, conjugated Fe.BLM A(5) and Co.BLM A(5) were both found to produce
      Form III DNA in addition to Form II DNA. The formation of Form III DNA by
      conjugated Fe.BLM A(5) was assessed quantitatively. When corrected for
      differences in the intrinsic efficiencies of DNA cleavage by conjugated vs free
      BLMs, conjugated Fe.BLM A(5) was found to produce Form III DNA to about the same
      extent as the respective free Fe.BLM A(5), arguing that this conjugated BLM can
      also effect double-strand cleavage of DNA. Although previous evidence supporting
      DNA intercalation by some metallobleomycins is convincing, the present evidence
      indicates that threading intercalation is not a requirement for DNA cleavage by
      Fe(II).BLM A(5), Co(III).BLM A(5), or Cu(I).BLM A(5).

PMID- 11457378
TI  - A triply templated artificial beta-sheet.
AB  - This paper describes the design, synthesis, and structural evaluation of a
      compound (4) comprising three molecular templates and a peptide strand that
      mimics a three-stranded protein beta-sheet. Two of the templates mimic the
      hydrogen-bonding functionality of peptide beta-strands and serve as the top and
      bottom strands by embracing the peptide strand, which is located in the middle of
      the sheet. The remaining template holds the three strands next to each other. The
      synthesis of artificial beta-sheet 4 begins with the bottom template and involves
      the sequential addition of the middle and top strands. (1)H NMR chemical shift
      and NOE studies establish that this compound folds to adopt a hydrogen-bonded
      beta-sheetlike structure in CDCl(3) solution. Chemical shift studies indicate
      that triply stranded artificial beta-sheet 4 is more tightly folded than its
      smaller doubly stranded homologue, artificial beta-sheet 1.

PMID- 11457379
TI  - Oxygen-dependent DNA damage amplification involving 5,6-dihydrothymidin-5-yl in a
      structurally minimal system.
AB  - 5,6-Dihydrothymidin-5-yl (1) was independently generated in a dinucleotide from a
      phenyl selenide precursor (4). Under free radical chain propagation conditions,
      the products resulting from hydrogen atom donation and radical-pair reaction are
      the major observed products in the absence of O(2). The stereoselectivity of the
      trapping process is dependent on the structure of the hydrogen atom donor. No
      evidence for internucleotidyl hydrogen atom abstraction by 1 was detected. The
      tandem lesion (17) resulting from hydrogen atom abstraction from the C1' position
      of the adjacent 2'-deoxyuridine by the peroxyl radical derived from 1 (3) is
      observed under aerobic conditions. The structure of this product is confirmed by
      independent synthesis and its transformation into a second independently
      synthesized product (24). Internucleotidyl hydrogen atom abstraction is effected
      selectively by the 5S-diastereomer of the peroxyl radical. The formation of
      dinucleotide 17 provides further support for the novel O(2)-dependent DNA damage
      amplification mechanism involving 1 reported previously (Greenberg, M. M.; et al.
      J. Am. Chem. Soc. 1997, 119, 1828).

PMID- 11457380
TI  - Conrotatory photochemical ring opening of alkylcyclobutenes in solution. A test
      of the hot ground-state mechanism.
AB  - Quantum yields for photochemical ring opening of six alkylcyclobutenes have been
      measured in hexane solution using 228-nm excitation, which selectively populates
      the lowest pi,R(3s) excited singlet states of these molecules and has been shown
      previously to lead to ring opening with clean conrotatory stereochemistry. The
      compounds studied in this work-1,2-dimethylcyclobutene (1), cis- and trans
      1,2,3,4-tetramethylcyclobutene (cis- and trans-5), hexamethylcyclobutene (8), and
      cis- and trans-tricyclo[6.4.0.0(2,7)]dodec-1(2)-ene (cis- and trans-9)-were
      selected so as to span a broad range in molecular weight and as broad a range as
      possible in Arrhenius parameters for thermal (ground-state) ring opening. RRKM
      calculations have been carried out to provide estimates of the rate constants for
      ground-state ring opening of each of the compounds over a range of thermal
      energies from 20 000 to 49 000 cm(-1). These have been used to estimate upper
      limits for the quantum yields of ring opening via a hot ground-state mechanism,
      assuming a value of k(deact) = 10(11) s(-1) for the rate constant for collisional
      deactivation by the solvent, that internal conversion to the ground state from
      the lowest Rydberg state occurs with close to unit efficiency, and that ergodic
      behavior is followed. The calculated quantum yields are significantly lower than
      the experimental values in all cases but one (1). This suggests that the Rydberg
      derived ring opening of alkylcyclobutenes is a true excited-state process and
      rules out the hot ground-state mechanism for the reaction.

PMID- 11457381
TI  - Electronic transduction of DNA sensing processes on surfaces: amplification of
      DNA detection and analysis of single-base mismatches by tagged liposomes.
AB  - Tagged, negatively charged, liposomes are used to amplify DNA sensing processes.
      The analyses of the target DNA are transduced electrochemically by using Faradaic
      impedance spectroscopy, or by microgravimetric measurements with Au-quartz
      crystals. By one method, a probe oligonucleotide (1) is assembled on Au
      electrodes or Au-quartz crystals. The formation of the double-stranded assembly
      with the analyte DNA (2) is amplified by the association of the 3-oligonucleotide
      functionalized liposomes to the sensing interface. The target DNA is analyzed by
      this method with a sensitivity limit that corresponds to 1 x 10(-12) M. A second
      method to amplify the sensing of the analyte involves the interaction of the 1
      functionalized electrode or Au-quartz crystal with the target DNA sample (2) that
      is pretreated with the biotinylated oligonucleotide (4). The formation of the
      three-component double-stranded assembly between 1/2/4 is amplified by the
      association of avidin and biotin-labeled liposomes to the sensing interfaces. By
      the secondary association of avidin and biotin-tagged liposomes, a dendritic-type
      amplification of the analysis of the DNA is accomplished. The analyte DNA (2) is
      sensed by this method with a sensitivity limit corresponding to 1 x 10(-13) M.
      The biotin-tagged liposomes are also used to probe and amplify single-base
      mismatches in an analyte DNA. The 6-oligonucleotide-functionalized Au-electrode
      or Au-quartz crystal was used to differentiate the single-base mismatch (G) in
      the mutant (5) from the normal A-containing gene (5a). Polymerase-induced
      coupling of the biotinylated-C-base to the double-stranded assembly generated
      between 6 and 5 followed by the association of avidin and biotin-tagged liposomes
      is used to probe the single base mismatch. The functionalized liposomes provide a
      particulate building unit for the dendritic amplification of DNA sensing.

PMID- 11457382
TI  - Incorporating beta-turns and a turn mimetic out of context in loop 1 of the WW
      domain affords cooperatively folded beta-sheets.
AB  - To probe the conformational requirements of loop 1 in the Pin1 WW domain, the
      residues at the i + 2 and i + 3 positions of a beta-turn within this loop were
      replaced by dPro-Gly and Asn-Gly, which are known to prefer the conformations
      required at the i + 1 and i + 2 positions of type II' and type I' beta-turns.
      Conformational specificity or lack thereof was further examined by incorporating
      into the i + 2 and i + 3 positions a non-alpha-amino acid-based beta-turn mimetic
      (4-(2'-aminoethyl)-6-dibenzofuran propionic acid residue, 1), which was designed
      to replace the i + 1 and i + 2 positions of beta-turns. All these Pin WW variants
      are monomeric and folded as discerned by analytical ultracentrifugation, NMR, and
      CD. They exhibit cooperative two-state transitions and display thermodynamic
      stability within 0.5 kcal/mol of the wild-type WW domain, demonstrating that the
      acquisition of native structure and stability does not require a specific
      sequence and, by extension, conformation within loop 1. However, it could be that
      these loop 1 mutations alter the kinetics of antiparallel beta-sheet folding,
      which will be addressed by subsequent kinetic studies.

PMID- 11457383
TI  - Chiral softballs: synthesis and molecular recognition properties.
AB  - Studies on the different congeners of the softball were undertaken to explore
      structural variants for enantioselective encapsulation. Two different spacer
      elements in the monomeric subunit render the dimeric softball chiral although the
      monomer itself is achiral. The dimers represent capsules with dissymmetric
      cavities with volumes ranging from 190 to 390 A(3). The cavities are distorted
      spheres, and asymmetric guests, such as naturally occurring terpenes, generally
      prefer one enantiomer of the capsule to its mirror image. The selectivities are
      moderate (up to 4:1). The complexation studies show that the host capsules are
      flexible enough to arrange themselves comfortably around a guest but still
      maintain enough rigidity to be influenced by the occupancy of a chiral guest. The
      enantiomeric capsules can interconvert (racemize) by dissociation and
      recombination of their subunits.

PMID- 11457384
TI  - Use of MM-PBSA in reproducing the binding free energies to HIV-1 RT of TIBO
      derivatives and predicting the binding mode to HIV-1 RT of efavirenz by docking
      and MM-PBSA.
AB  - In this work, a new ansatz is presented that combines molecular dynamics
      simulations with MM-PBSA (Molecular Mechanics Poisson-Boltzmann/surface area) to
      rank the binding affinities of 12 TIBO-like HIV-1 RT inhibitors. Encouraging
      results have been obtained not only for the relative binding free energies, but
      also for the absolute ones, which have a root-mean-square deviation of 1.0
      kcal/mol (the maximum error is 1.89 kcal/mol). Since the root-mean-square error
      is rather small, this approach can be reliably applied in ranking the ligands
      from the databases for this important target. Encouraged by the results, we
      decided to apply MM-PBSA combined with molecular docking to determine the binding
      mode of efavirenz SUSTIVA(TM) another promising HIV-1 RT inhibitor for which no
      ligand-protein crystal structure had been published at the time of this work. To
      proceed, we define the following ansatz: Five hundred picosecond molecular
      dynamics simulations were first performed for the five binding modes suggested by
      DOCK 4.0, and then MM-PBSA was carried out for the collected snapshots. MM-PBSA
      successfully identified the correct binding mode, which has a binding free energy
      about 7 kcal/mol more favorable than the second best mode. Moreover, the
      calculated binding free energy (-13.2 kcal/mol) is in reasonable agreement with
      experiment (-11.6 kcal/mol). In addition, this procedure was also quite
      successful in modeling the complex and the structure of the last snapshot was
      quite close to that of the measured 2,3 A resolution crystal (structure the root
      mean-square deviation of the 54 C(alpha) around the binding site and the
      inhibitor is 1.1 A). We want to point out that this result was achieved without
      prior knowledge of the structure of the efavirenz/RT complex. Therefore,
      molecular docking combined with MD simulations followed by MM-PBSA analysis is an
      attractive approach for modeling protein complexes a priori.

PMID- 11457385
TI  - Self-assembly of beta-sheets into nanostructures by poly(alanine) segments
      incorporated in multiblock copolymers inspired by spider silk.
AB  - Selective replacement of the amorphous peptide domain of a spider silk with
      poly(ethylene glycol) gave N. clavipes silk-inspired polymers having similar
      solid-state structures and very good mechanical properties. The tendency of
      poly(alanine) having appropriate chain length to form beta-sheets and the
      facility with which the beta-sheets self-assemble have been retained in the
      polymers. Solid-state (13)C NMR, solid-state FTIR, X-ray diffraction, and AFM
      studies showed that the polymers formed predominantly antiparallel beta-sheets
      that self-assembled into discrete nanostructures. The longer the peptide segment
      was, the greater was the tendency to self-assemble into antiparallel beta-sheet
      aggregates. AFM revealed that the morphology of the polymers was a microphase
      separated architecture that contained irregularly shaped 100-200 nm poly(alanine)
      nanodomains interspersed within the PEG phase. The results suggest that the
      poly(alanine) domain influences the solid-state properties of spider silk through
      beta-sheet self-assembly into temporary cross-links. The results further
      demonstrate that by selectively replacing certain segments of a naturally
      occurring biopolymer with a judiciously selected nonnative segment while, at the
      same time, retaining other segments known to be critical for the essential
      properties of the native biopolymer, a synthetic polymer with similar properties
      and function can be obtained.

PMID- 11457386
TI  - Co-conformational variability of cyclodextrin complexes studied by induced
      circular dichroism of azoalkanes.
AB  - The solution structures of the beta-cyclodextrin complexes between 2,3
      diazabicyclo[2.2.2]oct-2-ene (1) and its 1-isopropyl-4-methyl derivative 2 have
      been investigated by means of induced circular dichroism (ICD) and MM3-92 force
      field calculations, which considered the effect of solvation within a continuum
      approximation. Of primary interest was the so-called co-conformation of the host
      guest complex, i.e., the relative orientation of the guest within the host. A
      pool of low-energy complex structures, which were located by means of a Monte
      Carlo simulated annealing routine, was generated to evaluate the dynamic co
      conformational variability of the complexes. The ICD effects were calculated for
      the computed low-energy structures by applying a semiempirical method. The
      experimental and theoretical ICD as well as the calculated low-energy complex
      geometries suggest solution co-conformations in which the parent compound 1
      adapts a lateral arrangement with the ethano bridge of the guest penetrating
      deepest into the cavity and the azo group aligning parallel to the plane of the
      upper rim. In contrast, the alkyl derivative 2 prefers a frontal co-conformation
      with the isopropyl group penetrating deepest into the cavity and the azo group
      aligning perpendicular to the plane of the upper rim. The validity of the
      predictions of the Harata rule regarding the sign and the intensity of the ICD
      signals for the n(-)pi, n(+)pi, and pipi transition of the azo chromophore in
      dependence on the complex co-conformation are discussed. With respect to the co
      conformational variability of the complexes of the two azoalkanes, it was
      observed that the nearly spherical guest 1 forms a geometrically better defined
      complex than the sterically biased, alkyl-substituted derivative 2. This
      dichotomy is attributed to the largely different modes of binding for azoalkanes
      1 and 2. It is concluded that the goodness-of-fit in a host-guest complex cannot
      be directly related to the "tightness-of-fit".

PMID- 11457387
TI  - Insights into long-range structural effects on the stereochemistry of aldol
      condensations: a practical total synthesis of desoxyepothilone F.
AB  - A processable total synthesis of a potent antitumor agent, desoxyepothilone F
      (dEpoF, 21-hydroxy-12,13-desoxyepothilone B, 21-hydroxyepothilone D), has been
      accomplished. The route is highly convergent. The new technology has also been
      applied to a total synthesis of 12,13-desoxyepothilone (dEpoB). The crucial point
      of departure from previous syntheses of dEpoB and dEpoF involves presentation of
      the C1-C11 sector for Suzuki coupling with C3 in reduced form. Hitherto, the
      required S stereochemistry at C3 had been implemented via reduction of a keto
      function after Suzuki coupling. Whereas that chemistry worked quite well in a
      synthesis of dEpoB, it was not transferable to a high-yielding synthesis of
      dEpoF. The reduction of the keto group at C3 via a Noyori protocol after Suzuki
      coupling had proved to be very difficult. In our current approach, two
      consecutive aldol reactions are used to fashion the acyl sector. In the first
      aldol condensation, C6 becomes attached to C7. Following protection at C7, a two
      carbon acetate equivalent is used to join C2 and C3 with very high asymmetric
      induction at C3. Only after this center has been implemented is the Suzuki
      reaction conducted. This major advance allowed us to synthesize dEpoF in a
      straightforward fashion. These findings found ready application in the total
      synthesis of dEpoB. Another part of the study involved analysis of the factors
      associated with aldol condensations joining C6 to C7. In the work described
      herein, the consequences of the status of C3 in promoting the C6-C7 aldol
      coupling are probed in detail. Dramatic stereochemical long-range effects
      uncovered during the study are described, and a working model to explain these
      effects has emerged.

PMID- 11457388
TI  - Amino acid catalyzed direct asymmetric aldol reactions: a bioorganic approach to
      catalytic asymmetric carbon-carbon bond-forming reactions.
AB  - Direct asymmetric catalytic aldol reactions have been successfully performed
      using aldehydes and unmodified ketones together with commercially available
      chiral cyclic secondary amines as catalysts. Structure-based catalyst screening
      identified L-proline and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) as the
      most powerful amino acid catalysts for the reaction of both acyclic and cyclic
      ketones as aldol donors with aromatic and aliphatic aldehydes to afford the
      corresponding aldol products with high regio-, diastereo-, and
      enantioselectivities. Reactions employing hydroxyacetone as an aldol donor
      provide anti-1,2-diols as the major product with ee values up to >99%. The
      reactions are assumed to proceed via a metal-free Zimmerman-Traxler-type
      transition state and involve an enamine intermediate. The observed
      stereochemistry of the products is in accordance with the proposed transition
      state. Further supporting evidence is provided by the lack of nonlinear effects.
      The reactions tolerate a small amount of water (<4 vol %), do not require inert
      reaction conditions and preformed enolate equivalents, and can be conveniently
      performed at room temperature in various solvents. In addition, reaction
      conditions that facilitate catalyst recovery as well as immobilization are
      described. Finally, mechanistically related addition reactions such as ketone
      additions to imines (Mannich-type reactions) and to nitro-olefins and alpha,beta
      unsaturated diesters (Michael-type reactions) have also been developed.

PMID- 11457389
TI  - Asymmetric hydrogenation of enamides with Rh-BisP and Rh-miniPHOS catalysts.
      scope, limitations, and mechanism.
AB  - The asymmetric hydrogenation of aryl- and alkyl-substituted enamides catalyzed by
      Rh-BisP complex affords optically active amides with very high ee values. The Rh
      MiniPHOS catalyst gives somewhat less satisfactory results. Hydrogenation of the
      aryl-substituted enamides with (S,S)-BisP-Rh catalyst gives R-amides, whereas the
      t-Bu- and 1-adamantyl-substituted enamides give S-products with 99% ee. Reaction
      of [Rh(BisP)(CD(3)OD)(2)]BF(4) (11) with CH(2)=C(C(6)H(5))NHCOCH(3) (5) gives two
      diastereomers of the catalyst-substrate complex (12a,b), which interconvert
      reversibly by both intra- and intermolecular pathways as shown by EXSY data. Only
      one isomer in equilibrium with solvate complex 11 was detected for each of the
      catalyst-substrate complexes 17 and 18 obtained from CH(2)=C(t-Bu)NHCOCH(3) (6)
      or CH(2)=C(1-adamantyl)NHCOCH(3) (7). Hydrogenation of these equilibrium mixtures
      at -100 degrees C gave monohydride intermediates 19 and 20, respectively. In
      these monohydrides the Rh atom is bound to the beta-carbon. A new effect of the
      significant decrease of ee was found for the asymmetric hydrogenation of
      CH(2)=C(C(6)H(4)OCH(3)-o)NHCOCH(3) (21), when H(2) was substituted for HD or
      D(2).

PMID- 11457390
TI  - Probing the donor-acceptor proximity on the physicochemical properties of
      porphyrin-fullerene dyads: "tail-on" and "tail-off" binding approach.
AB  - A new approach of probing proximity effects in porphyrin-fullerene dyads by using
      an axial ligand coordination controlled "tail-on" and "tail-off" binding
      mechanism is reported. In the newly synthesized porphyrin-fullerene dyads for
      this purpose, the donor-acceptor proximity is controlled either by temperature
      variation or by an axial ligand replacement method. In o-dichlorobenzene, 0.1 M
      (TBA)ClO(4), the synthesized zincporphyrin-fullerene dyads exhibit seven one
      electron reversible redox reactions within the accessible potential window of the
      solvent and the measured electrochemical redox potentials and UV-visible
      absorption spectra reveal little or no ground-state interactions between the
      C(60) spheroid and porphyrin pi-system. The proximity effects on the photoinduced
      charge separation and charge recombination are probed by both steady-state and
      time-resolved fluorescence techniques. It is observed that in the "tail-off" form
      the charge-separation efficiency changes to some extent in comparison with the
      results obtained for the "tail-on" form, suggesting the presence of some through
      space interactions between the singlet excited zinc porphyrin and the C(60)
      moiety in the "tail-off" form. The charge separation rates and efficiencies are
      evaluated from the fluorescence lifetime studies. The charge separation via the
      singlet excited states of zinc porphyrin in the studied dyads is also confirmed
      by the quick rise-decay of the anion radical of the C(60) moiety within 20 ns.
      Furthermore, a long-lived ion pair with lifetime of about 1000 ns is also
      observed in the investigated zinc porphyrin-C(60) dyads.

PMID- 11457391
TI  - Solid-state NMR detection, characterization, and quantification of the multiple
      aluminum environments in US-Y catalysts by (27)Al MAS and MQMAS experiments at
      very high field.
AB  - The detection of all of the aluminum present in steamed zeolite H-Y catalysts by
      (27)Al MAS NMR at 14.4 T (600 MHz for (1)H) and 18.8T (800 MHz for (1)H) is
      reported. Further, it is shown that it is possible by (27)Al MAS and MQMAS NMR
      measurements to clearly identify four separate aluminum environments which are
      characteristic of these materials and to unambiguously assign their
      coordinations. Average chemical shift and quadrupolar coupling parameters are
      used to accurately simulate the (27)Al MAS NMR spectra at 9.4 T (400 MHz for
      (1)H), 14.4 T (600 MHz for (1)H) and 18.8 T (800 MHz for (1)H) in terms of these
      four aluminum environments. In addition, these average chemical shift and
      quadrupolar coupling parameters are used to calculate peak positions in the
      (27)Al MQMAS isotropic dimension that are in good agreement with the experimental
      data acquired at 9.4 and 18.8 T.

PMID- 11457392
TI  - Role of alkali metal cation size in the energy and rate of electron transfer to
      solvent-separated 1:1 [(M+)(acceptor)] (M+ = Li+, Na+, K+) ion pairs.
AB  - The effect of cation size on the rate and energy of electron transfer to
      [(M(+))(acceptor)] ion pairs is addressed by assigning key physicochemical
      properties (reactivity, relative energy, structure, and size) to an isoelectronic
      series of well-defined M(+)-acceptor pairs, M(+) = Li(+), Na(+), K(+). A 1e(-)
      acceptor anion, alpha-SiV(V)W(11)O(40)(5-) (1, a polyoxometalate of the Keggin
      structural class), was used in the 2e(-) oxidation of an organic electron donor,
      3,3',5,5'-tetra-tert-butylbiphenyl-4,4'-diol (BPH(2)), to 3,3',5,5'-tetra-tert
      butyldiphenoquinone (DPQ) in acetate-buffered 2:3 (v/v) H(2)O/t-BuOH at 60
      degrees C (2 equiv of 1 are reduced by 1e(-) each to 1(red), alpha
      SiV(IV)W(11)O(40)(6-)). Before an attempt was made to address the role of cation
      size, the mechanism and conditions necessary for kinetically well behaved
      electron transfer from BPH(2) to 1 were rigorously established by using GC-MS,
      (1)H, (7)Li, and (51)V NMR, and UV-vis spectroscopy. At constant [Li(+)] and
      [H(+)], the reaction rate is first order in [BPH(2)] and in [1] and zeroth order
      in [1(red)] and in [acetate] (base) and is independent of ionic strength, mu. The
      dependence of the reaction rate on [H(+)] is a function of the constant, K(a)1,
      for acid dissociation of BPH(2) to BPH(-) and H(+). Temperature dependence data
      provided activation parameters of DeltaH = 8.5 +/- 1.4 kcal mol(-1) and DeltaS = 
      39 +/- 5 cal mol(-1) K(-1). No evidence of preassociation between BPH(2) and 1
      was observed by combined (1)H and (51)V NMR studies, while pH (pD)-dependent
      deuterium kinetic isotope data indicated that the O-H bond in BPH(2) remains
      intact during rate-limiting electron transfer from BPH(2) and 1. The formation of
      1:1 ion pairs [(M(+))(SiVW(11)O(40)(5-))](4-) (M(+)1, M(+) = Li(+), Na(+), K(+))
      was demonstrated, and the thermodynamic constants, K(M)(1), and rate constants,
      k(M)(1), associated with the formation and reactivity of each M(+)1 ion pair with
      BPH(2) were calculated by simultaneous nonlinear fitting of kinetic data
      (obtained by using all three cations) to an equation describing the rectangular
      hyperbolic functional dependence of k(obs) values on [M(+)]. Constants,
      K(M)(1)red, associated with the formation of 1:1 ion pairs between M(+) and
      1(red) were obtained by using K(M)(1) values (from k(obs) data) to simultaneously
      fit reduction potential (E(1/2)) values (from cyclic voltammetry) of solutions of
      1 containing varying concentrations of all three cations to a Nernstian equation
      describing the dependence of E(1/2) values on the ratio of thermodynamic
      constants K(M)(1) and K(M)(1)red. Formation constants, K(M)(1), and K(M)(1)red,
      and rate constants, k(M)(1), all increase with the size of M(+) in the order
      K(Li)(1) = 21 < K(Na)(1) = 54 < K(K)(1) = 65 M(-1), K(Li)(1)red = 130 <
      K(Na)(1)red = 570 < K(K)(1)red = 2000 M(-1), and k(Li)(1) = 0.065 < k(Na)(1) =
      0.137 < k(K)(1) = 0.225 M(-1) s(-1). Changes in the chemical shifts of (7)Li NMR
      signals as functions of [Li(5)1] and [Li(6)1(red)] were used to establish that
      the complexes M(+)1 and M(+)1(red) exist as solvent-separated ion pairs. Finally,
      correlation between cation size and the rate and energy of electron transfer was
      established by consideration of K(M)(1), k(M)(1), and K(M)(1)red values along
      with the relative sizes of the three M(+)1 pairs (effective hydrodynamic radii,
      r(eff), obtained by single-potential step chronoamperometry). As M(+) increases
      in size, association constants, K(M)(1), become larger as smaller, more intimate
      solvent-separated ion pairs, M(+)1, possessing larger electron affinities (q/r),
      and associated with larger k(M)(1)() values, are formed. Moreover, as M(+)1 pairs
      are reduced to M(+)1(red) during electron transfer in the activated complexes,
      [BPH(2), M(+)1], contributions of ion pairing energy (proportional to -RT
      ln(K(M)(1)red/K(M)(1)) to the standard free energy change associated with
      electron transfer, DeltaG degrees (et), increase with cation size: -RT
      ln(K(M)(1)red/K(M)(1)) (in kcal mol(-1)) = -1.2 for Li(+), -1.5 for Na(+), and 
      2.3 for K(+).

PMID- 11457393
TI  - Surface control of oxidation by an adsorbed Ru(IV)-oxo complex.
AB  - When adsorbed to optically transparent, thin films of TiO(2) nanoparticles on
      glass, the aqua complex [Ru(II)(tpy)(bpy(PO(3)H(2))(2))(OH(2))](2+)
      (bpy(PO(3)H(2))(2) is 2,2'-bipyridyl-4,4'-diphosphonic acid; tpy is 2,2':6',2' '
      terpyridine) is oxidized by Ce(IV)(NH(4))(2)(NO(3))(6) in 0.1 M HClO(4) to its
      Ru(IV)=O(2+) form as shown by UV-visible measurements and analysis of oxidative
      equivalents by oxidation of hydroquinone to quinone. Kinetic studies on the
      oxidations of cyclohexene, benzyl alcohol, phenol, and trans-stilbene by surface
      bound Ru(IV)=O(2+) by UV-visible monitoring reveal direct evidence for initial 2
      electron steps to give Ru(II) intermediates in all four cases. These steps are
      masked in solution where Ru(IV) --> Ru(II) reduction is followed by rapid
      reactions between Ru(II) intermediates and Ru(IV)=O(2+) to give Ru(III).
      Reactions between Ru(II) and Ru(IV)=O(2+) on the surface are inhibited by binding
      to the surface, which restricts translational mobility. Rate constants on the
      surface and in solution are comparable, pointing to comparable reactivities. The
      surface experiments give unprecedented insight into oxidation mechanism with
      important implications for achieving product selectivity in synthesis by limiting
      oxidation to two electrons.

PMID- 11457394
TI  - A theoretical study on the origin of cooperativity in the formation of 3(10)- and
      alpha-helices.
AB  - By using a simple repeating unit method, we have conducted a theoretical study
      which delineates the preferences for beta-strand, 2(7)-ribbon, 3(10)-helix, and
      alpha-helix formation for a series of polyglycine models up to 14 amino acid
      residues (Ac-(Gly)(n), n = 0, 1, 2,., 14). Interactions among residues, which
      result in cooperativity, are clearly indicated by variations in calculated
      energies of the residues. Whereas no cooperativity is found in the formation of
      beta-strands and 2(7)-ribbons, there is a significant cooperativity in the
      formation of 3(10)- and alpha-helices, especially for the latter. In the case of
      alpha-helices, the 14th residue is more stable than the 3rd by about 3 kcal/mol.
      A good correlation between calculated residue energy and residue dipole moment
      was uncovered, indicating the importance of long-range electrostatic interactions
      to the cooperativity. The results of our calculations are compared with those of
      the AMBER and PM3 methods, and indicate that both methods, AMBER and PM3, need
      further development in the cooperative view of electrostatic interactions. The
      result should be of importance in providing insight into protein folding and
      formation of helical structures in a variety of polymeric compounds. This also
      suggests a strategy for the development of more consistent molecular mechanics
      force fields.

PMID- 11457395
TI  - A theoretical investigation of the remarkable nuclear spin-spin coupling pattern
      in [(NC)(5)Pt-Tl(CN)](-).
AB  - We address the problem of the interpretation of heavy nucleus spin-spin couplings
      for systems being studied in solution. Solvation can create counterintuitive
      features concerning the spin-spin couplings, which are enhanced by relativistic
      effects due to the presence of heavy nuclei. This should therefore be taken into
      consideration for the discussion of spectra obtained from solution. Evidence for
      such solvent effects is provided by a relativistic density functional study of
      [(NC)(5)Pt-Tl(CN)](-) (I). It is demonstrated that the remarkable experimentally
      observed spin-spin coupling pattern, e.g., (2)J(Tl-C) >> (1)J(Tl-C) and J(Pt-Tl)
      approximately 57 kHz, is semiquantitatively reproduced by our calculations if
      both relativistic effects and solvation are taken into account. Solvent effects
      are very substantial and shift the Pt-Tl coupling by more than 100%, e.g.
      Relativistic increase of s-orbital density at the heavy nuclei, charge donation
      by the solvent, and the specific features of the multicenter C-Pt-Tl-C bond are
      responsible for the observed coupling pattern.

PMID- 11457396
TI  - Pulsed EPR/ENDOR characterization of perturbations of the Cu(A) center ground
      state by axial methionine ligand mutations.
AB  - The effect of axial ligand mutation on the Cu(A) site in the recombinant water
      soluble fragment of subunit II of Thermus thermophilus cytochrome c oxidase ba(3)
      has been investigated. The weak methionine ligand was replaced by glutamate and
      glutamine which are stronger ligands. Two constructs, M160T0 and M160T9, that
      differ in the length of the peptide were prepared. M160T0 is the original soluble
      fragment construct of cytochrome ba(3) that encodes 135 amino acids of subunit
      II, omitting the transmembrane helix that anchors the domain in the membrane. In
      M160T9 nine C-terminal amino acids are missing, including one histidine. The
      latter has been used to reduce the amount of a secondary T2 copper which is most
      probably coordinated to a surface histidine in M160T0. The changes in the spin
      density in the Cu(A) site, as manifested by the hyperfine couplings of the weakly
      and strongly coupled nitrogens, and of the cysteine beta-protons, were followed
      using a combination of advanced EPR techniques. X-band ( approximately 9 GHz)
      electron-spin-echo envelope modulation (ESEEM) and two-dimensional (2D) hyperfine
      sublevel correlation (HYSCORE) spectroscopy were employed to measure the weakly
      coupled (14)N nuclei, and X- and W-band (95 GHz) pulsed electron-nuclear double
      resonance (ENDOR) spectroscopy for probing the strongly coupled (14)N nuclei and
      the beta-protons. The high field measurements were extremely useful as they
      allowed us to resolve the T2 and Cu(A) signals in the g( perpendicular) region
      and gave (1)H ENDOR spectra free of overlapping (14)N signals. The effects of the
      M160Q and M160E mutations were: (i) increase in A( parallel)((63,65)Cu), (ii)
      larger hyperfine coupling of the weakly coupled backbone nitrogen of C153, (iii)
      reduction in the isotropic hyperfine interaction, a(iso), of some of the beta
      protons making them more similar, (iv) the a(iso) value of one of the remote
      nitrogens of the histidine residues is decreased, thus distinguishing the two
      histidines, and finally, (v) the symmetry of the g-tensor remained axial. These
      effects were associated with an increase in the Cu-Cu distance and subtle changes
      in the geometry of the Cu(2)S(2) core which are consistent with the electronic
      structural model of Gamelin et al. (Gamelin, D. R.; Randall, D. W.; Hay, M. T.;
      Houser, R. P.; Mulder, T. C.; Canters, G. W.; de Vries, S.; Tolman, W. B.; Lu,
      Y.; Solomon, E. I. J. Am. Chem. Soc. 1998, 120, 5246-5263).

PMID- 11457397
TI  - Symmetry breaking in the relaxed S(1) excited state of bianthryl derivatives in
      weakly polar solvents.
AB  - The flash-photolysis time-resolved microwave conductivity technique (FP-TRMC) has
      been used to investigate the nature of the relaxed S(1) state of 9,9'-bianthryl
      (AA), 10-cyano-9,9'-bianthryl (CAA), and 10,10'-dicyano-9,9'-bianthryl (CAAC).
      Changes in both the real, Deltaepsilon' (dielectric constant), and imaginary,
      Deltaepsilon' ' (dielectric loss), components of the complex permittivity have
      been measured. The dielectric loss transients conclusively demonstrate the
      dipolar nature of S(1) for all three compounds in the pseudopolar solvents
      benzene and 1,4-dioxane, and even in the nonpolar solvents n-hexane and
      cyclohexane. The required symmetry breaking is considered to result from density
      and structural fluctuations in the solvent environment. The dipole relaxation
      times for AA (CAAC) are ca. 2 ps for the alkanes and 7.9 (5.3) and 14 (14) ps for
      benzene and dioxane, respectively. The time scale of dipole relaxation for the
      symmetrical compounds is much shorter than that for rotational diffusion and is
      attributed to intramolecular, flip-flop dipole reversal via a neutral excitonic
      state. The dipole moment of the transient dipolar state is estimated to be ca. 8
      D, that is much lower than the value of ca. 20 D determined from the
      solvatochromic shifts in the fluorescence in intermediate to highly polar
      solvents which corresponds to close to complete charge separation. For the
      asymmetric compound, CAA, a dipole moment close to 20 D is found in all solvents,
      including n-hexane. Dipole relaxation in this case occurs on a time scale of
      several hundred picoseconds and is controlled mainly by diffusional rotation of
      the molecules. The mechanism and kinetics of formation of the dipolar excited
      states are discussed in the light of these results.

PMID- 11457398
TI  - High dissolution and strong light emission of carbon nanotubes in aromatic amine
      solvents.

PMID- 11457399
TI  - Chain end-groups reveal two states for palladium-based polyketone catalyst
      species.

PMID- 11457400
TI  - alpha-Iminocarboxamidato-nickel(II) ethylene polymerization catalysts.

PMID- 11457401
TI  - Sensitizing DNA to secondary electron damage: resonant formation of oxidative
      radicals from 5-halouracils.

PMID- 11457402
TI  - Observation of the predicted negative Faraday A MCD term in a cyclobutadiene
      dianion.

PMID- 11457403
TI  - Rhodium-catalyzed coupling reactions of arylboronic acids to olefins in aqueous
      media.

PMID- 11457404
TI  - Critical difference in chiral recognition of N-Cbz-D/L-aspartic and -glutamic
      acids by mono- and bis(trimethylammonio)-beta-cyclodextrins.

PMID- 11457405
TI  - Lomaiviticins A and B, potent antitumor antibiotics from Micromonospora
      lomaivitiensis.

PMID- 11457406
TI  - Plasma-fluorination synthesis of high surface area aluminum trifluoride from a
      zeolite precursor.

PMID- 11457407
TI  - A new class of chiral lewis acid catalysts for highly enantioselective hetero
      Diels-Alder reactions: exceptionally high turnover numbers from dirhodium(II)
      carboxamidates.

PMID- 11457408
TI  - Multiple membranes from "true" polyelectrolyte multilayers.

PMID- 11457409
TI  - The first zeolite with three-dimensional intersecting straight-channel system of
      12-membered rings.

PMID- 11457410
TI  - A new general method for the preparation of metal carbene complexes.

PMID- 11457411
TI  - Cobalt-catalyzed tandem radical cyclization and cross-coupling reaction: its
      application to benzyl-substituted heterocycles.

PMID- 11457412
TI  - The structural and functional equivalence of aurophilic and hydrogen bonding:
      evidence for the first examples of rotator phases induced by aurophilic bonding.

PMID- 11457413
TI  - Substrate dependence of nonlinear effects: mechanistic probe and practical
      applications.

PMID- 11457414
TI  - Nativelike enzyme properties are important for optimum activity in neat organic
      solvents.

PMID- 11457415
TI  - Toward proteomimetics: terphenyl derivatives as structural and functional mimics
      of extended regions of an alpha-helix.

PMID- 11457417
TI  - Effect of lithium on phosphoinositide metabolism in human brain: a proton
      decoupled (31)P magnetic resonance spectroscopy study.
AB  - BACKGROUND: The objective of our study was to evaluate whether lithium increases
      brain phosphomonoester (PME) levels in human subjects. METHODS: Proton decoupled
      (31)P magnetic resonance spectra were obtained from eight healthy volunteers
      before and after the administration of lithium carbonate, 450 mg b.i.d., for 7
      and 14 days. RESULTS: Pairwise comparisons of the mole percent PME revealed a
      significant increase from baseline at day 7 and day 14 of lithium administration.
      CONCLUSIONS: An increase in PME concentration with 7 and 14 days of lithium
      administration in the human brain in vivo was observed. Because the inositol-1
      monophosphate contributes to the PME peak, this result suggests that some of the
      initial actions of lithium may occur through a reduction of myo-inositol, which
      in turn may initiate a cascade of secondary changes at different levels of signal
      transduction process and gene expression in brain, effects that are ultimately
      responsible for the therapeutic benefits of lithium.

PMID- 11457418
TI  - No evidence for in vivo regulation of midbrain serotonin transporter availability
      by serotonin transporter promoter gene polymorphism.
AB  - BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5
      HTTLPR) has been shown to influence the quantity of serotonin transporter
      expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated
      with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long
      allele (l). We performed a single photon emission computed tomography (SPECT)
      study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane
      ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects
      genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer
      injection, regions of interest anatomically corresponding to the thalamus
      hypothalamus and mesencephalon-pons areas were compared to the binding in the
      cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results
      expressed as target activity minus cerebellum activity/cerebellum activity). DNA
      from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard
      polymerase chain reaction methods. RESULTS: Specific binding ratios in the
      thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n =
      3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in
      subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons
      were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s;
      n = 4). None of these differences was statistically significant. CONCLUSIONS: Our
      data provide no evidence for in vivo functional regulation of 5-HTT availability
      by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy
      subjects.

PMID- 11457419
TI  - Is the beneficial antidepressant effect of coadministration of pindolol really
      due to somatodendritic autoreceptor antagonism?
AB  - BACKGROUND: We investigated the combination of selective serotonin reuptake
      inhibitors (SSRIs) with the beta-adrenoceptor/serotonin 1A (5-HT(1A)) antagonist
      pindolol, based on the concept that 5-HT(1A) receptor blockade would eliminate
      the need for desensitization of presynaptic 5-HT(1A) receptors and therefore
      hasten the onset of action and improve the efficacy of SSRIs. However, since
      pindolol plasma levels after 2.5 mg three times a day are about 60 nmol/L, and
      the K(i) for the 5-HT(1A) receptor is 30 nmol/L, it is questionable whether
      pindolol levels in the brain would be sufficient to antagonize 5-HT(1A)
      receptors. Using microdialysis in the guinea pig, we correlated brain and plasma
      levels of pindolol with its capability of augmenting paroxetine-induced increases
      in brain 5-HT levels. In addition, central beta-receptor antagonism of pindolol
      was studied by investigating blockade of beta-agonist-induced increases in brain
      cyclic adenosine monophosphate (cAMP) formation. METHODS: Using microdialysis and
      jugular vein catheterization, we studied the ability of systemically administered
      pindolol to antagonize central 5-HT(1A) and beta-adrenoceptors, while
      simultaneously monitoring pindolol plasma and brain concentrations. RESULTS:
      Augmentation of paroxetine-induced increases in extracellular 5-HT levels in the
      ventral hippocampus was only observed at steady state plasma levels exceeding
      7000 nmol/L (concurrent brain levels 600 nmol/L). In contrast, antagonism of beta
      agonist-induced increases of brain cAMP levels was already observed at pindolol
      plasma levels of 70 nmol/L (concurrent brain levels < 3 nmol/L). CONCLUSIONS: At
      plasma levels that are observed in patients after 2.5 mg three times a day (
      approximately 60 nmol/L), pindolol produces only a partial blockade of
      presynaptic 5-HT(1A) autoreceptors and does not augment the SSRI-induced 5-HT
      increase in the guinea pig brain. It is therefore very unlikely that the
      favorable effects of combining pindolol with SSRIs, as reported in a number of
      clinical studies, are due to 5-HT(1A) antagonism. Since pindolol completely
      blocks central beta-adrenoreceptors at clinically relevant plasma levels, it is
      possible that beta-adrenoceptor antagonism is involved in mediating pindolol's
      beneficial effects.

PMID- 11457420
TI  - Acute mood and thyroid stimulating hormone effects of transcranial magnetic
      stimulation in major depression.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has recently been
      demonstrated to have antidepressant effects. Some work suggests that rTMS over
      prefrontal cortex administered to healthy individuals produces acute elevations
      of mood and serum thyroid-stimulating hormone (TSH). We sought to determine
      whether single rTMS sessions would produce acute mood and serum TSH elevations in
      subjects with major depressions. METHODS: Under double-blind conditions et al 14
      medication-free subjects with major depression received individual sessions of
      either active or sham rTMS. rTMS was administered over the left prefrontal cortex
      at 10 Hz et al 100% of motor threshold, 20 trains over 10 min. Immediately before
      and after rTMS sessions, subjects' mood was rated with the Profile of Mood States
      (POMS) and the 6-Item Hamilton Depression Scale, and blood was drawn for later
      analysis of TSH. Subjects and raters were blind to treatment assignment. RESULTS:
      The group receiving active stimulation manifested significantly greater
      improvement on the POMS subscale of Depression (p < or = .0055) and a trend
      toward greater improvement on the modified Hamilton Rating (.05 < p < or =.1). No
      hypomania was induced. The change in TSH from pre- to post-rTMS was significantly
      different between active and sham sessions. CONCLUSIONS: This blinded, placebo
      controlled trial documents that individual rTMS sessions can acutely elevate mood
      and stimulate TSH release in patients experiencing major depressive episodes.

PMID- 11457421
TI  - Increased vagal tone during winter in subsyndromal seasonal affective disorder.
AB  - BACKGROUND: Seasonal affective disorder (SAD) is characterized by recurrent
      winter depression with summer remissions and/or hypomania. Further symptoms
      include hypersomnia, increased appetite, weight gain, fatigue, and social
      withdrawal, which may indicate autonomic changes during winter. METHODS:
      Measurements of respiratory sinus arrhythmia, heart rate (HR), and skin
      conductance level (SCL) were taken from 32 participants in subsyndromal SAD and
      control groups (eight male and eight female subjects in each group) in autumn and
      winter to determine any change in autonomic function. Measures were taken at
      baseline and during two stressor tasks. Single determinations of blood pressure,
      sublingual temperature, depression, aerobic fitness, and body mass index were
      also measured at each session. Replication in a second data collection period
      over subsequent winter and spring periods was conducted with an additional 32
      participants to extend the findings and to counterbalance order effects in
      testing. Data were combined to produce "winter" and "nonwinter" test periods and
      statistically corrected for testing order. RESULTS: Respiratory sinus arrhythmia
      differences indicated that SAD subjects have increased vagal tone in winter. Both
      groups show a decrease for HR and increases for SCL and diastolic blood pressure
      in winter. CONCLUSIONS: Seasonal affective disorder may show similarities with
      hibernation, and the results may indicate mechanisms different from those of
      nonseasonal depression.

PMID- 11457422
TI  - Cognitive disturbance in outpatient depressed younger adults: evidence of modest
      impairment.
AB  - BACKGROUND: Investigations of cognitive disturbances among patients with mood
      disorders have yielded inconsistent results. Although marked neuropsychologic
      deficits have been reported in elderly patients and in midlife patients with
      severe depression, the severity of cognitive impairments in medically healthy
      younger ambulatory adults with depression has not been well characterized.
      METHODS: A comprehensive battery of standard neuropsychologic tests and
      experimental computerized measures of cognitive functioning were administered to
      unmedicated ambulatory younger adults with mild to moderate nonbipolar depression
      and to a group of age- and gender-equated healthy subjects. RESULTS: Patients
      demonstrated a notable absence of widespread cognitive impairment. Deficits in
      executive functions were observed on the Wisconsin Card Sort Test but not on
      several other tests. Despite the absence of significant impairment on tests of
      attention, memory, and motor performance in the total sample, symptom severity
      and age of illness onset were correlated with poorer performance on some tests of
      cognitive functioning even after correction for age. CONCLUSIONS: These findings,
      derived from a large sample of unmedicated depressed outpatients, indicate that
      major depressive disorder in healthy younger ambulatory adults does not cause
      appreciable impairments in cognitive functioning in the absence of clinical and
      course-of-illness features.

PMID- 11457423
TI  - Attention shifts and anticipatory mechanisms in hyperactive children: an ERP
      study using the Posner paradigm.
AB  - BACKGROUND: The aim of this study was to assess attentional, decisional, and
      motor processing stages during the performance of an attention shifting paradigm,
      both in normal children and children with attention-deficit/hyperactivity
      disorder (ADHD). METHODS: We recorded event-related potentials (ERPs) and
      performance measures during a variant of the Posner paradigm in 13 control
      subjects and 24 ADHD children. Subjects responded with a spatially concordant
      motor response to left or right visual targets, which could be either preceded by
      a spatial cue ("valid" = same side; "invalid" = opposite side) or presented
      uncued. RESULTS: Patients made significantly more errors than control subjects,
      with predominance of the anticipatory type. As compared to control subjects, ADHD
      children had faster reaction times, as well as a shortened interval between the
      N2 and P3 ERPs and the motor response. Patients also showed a decreased
      attentional priming effect on early sensory responses (P1). Finally, the slow
      negativity (contingent negative variation/readiness potential) that preceded the
      target in the "no cue" condition was absent in ADHD patients. CONCLUSIONS: The
      combined analysis of electrophysiological and behavioral data suggest a
      characteristic mode of response of ADHD in attention shifting tasks,
      characterized by "motor impulsivity" with release of motor responses before
      stimulus processing is adequately completed, as well as a lack of strategic
      planning/anticipatory mechanisms in the absence of warning stimulus. These
      deficits may be partly attributed to dysmaturation of executive frontal
      functions. In addition, a minor deficit in early attentional priming was also
      observed in ERPs, with no apparent behavioral counterparts.

PMID- 11457424
TI  - Transcranial magnetic stimulation in therapy studies: examination of the
      reliability of "standard" coil positioning by neuronavigation.
AB  - Transcranial magnetic stimulation is investigated as a new tool in the therapy of
      depression and other psychiatric disorders. In almost all studies, the
      dorsolateral prefrontal cortex (DLPFC) has been selected as the target site for
      stimulation. Usually this region was determined by identifying the patient's
      motor cortex, and from there the coil was placed 5 cm rostrally. The aim of our
      study was to test the reliability of this standard procedure. A neuronavigational
      system was used to relate the final coil position after applying the standard
      procedure to the individual cortical anatomy. In 7 of 22 subjects, the Brodman
      area 9 of the DLPFC was targeted correctly in this manner. In 15 subjects, the
      center of the coil was found to be located more dorsally (e.g., above the
      premotor cortex). The current method for locating the DLPFC is not precise
      anatomically and may be improved by navigating procedures taking individual
      anatomy into account.

PMID- 11457425
TI  - Suicide, impulsive aggression, and HTR1B genotype.
AB  - BACKGROUND: Suicidality and impulsive aggression are partially heritable, and
      postmortem brain studies suggest that abnormalities in serotonin 1B may be
      associated with suicide. Studies of serotonin 1B "knockout" mice show an increase
      in aggressive behavior relative to wild-type mice. METHODS: We assessed the
      relationship between genotype at the HTR1B locus and both suicide history and
      impulsive aggression in personality disorders. RESULTS: The "G" allele of a
      polymorphic gene at the HTR1B locus was associated with a history of suicide
      attempts in white patients with personality disorders [chi(2)(1) = 9.3, p =.01, n
      = 90]. No relationship was found between HTR1B genotype and self-reported
      impulsive aggression. CONCLUSIONS: This preliminary finding suggests that allelic
      variability at the HTR1B locus may be associated with the susceptibility to
      suicide attempts in patients with personality disorders.

PMID- 11457426
TI  - Differential roles of cyclooxygenase isoforms after kainic acid-induced
      prostaglandin E(2) production and neurodegeneration in cortical and hippocampal
      cell cultures.
AB  - Prostaglandins, which are cyclooxygenase (COX) products, are pathologically up
      regulated, and have been proven to be closely associated with neuronal death. In
      this study, we investigated a role of COX isoforms (COX-1 and COX-2) in kainic
      acid-induced neuronal death in cultured murine cortical or hippocampal neurons.
      In primary cortical neurons, both indomethacin (COX-1/-2 nonselective inhibitor)
      and aspirin (COX-1 preferential inhibitor) reduced basal and kainic acid-induced
      PGE(2) production significantly and prevented neuronal cell death after kainic
      acid treatment. In contrast, NS398 (COX-2 selective inhibitor) had no effect on
      kainic acid-induced neuronal cell death. In hippocampal neurons, however, COX-2
      inhibitors prevented both kainic acid-induced neuronal death and PGE(2)
      production. COX-2 expression was remarkably up-regulated by kainic acid in
      hippocampal neurons; whereas in cortical neurons, COX-2 expression was
      comparatively less significant. Astrocytes were unresponsive to kainic acid in
      terms of PGE(2) production and cell death. In conclusion, we suggest that the
      release of PGE(2) induced by kainic acid occurred through COX-1 activity rather
      than COX-2 in cortical neurons. The inhibition of PGE(2) release by COX-1
      inhibitors prevented kainic acid-induced cortical neuronal death, while in the
      hippocampal neurons, COX-2 inhibitors prevented kainic acid-induced PGE(2)
      release and hippocampal neuronal death.

PMID- 11457427
TI  - Nitric oxide synthase in the hypothalamic paraventricular nucleus of the female
      rat; organization of spinal projections and coexistence with oxytocin or
      vasopressin.
AB  - We investigated the distributions and interrelations of neuronal nitric oxide
      (NO) synthase- (nNOS), oxytocin- (OT), and 8-arginine vasopressin- (AVP)
      immunoreactive (IR) neurons in the paraventricular nucleus (PVN), and the
      occurrence and distribution of nNOS spinally projecting neurons in the PVN of the
      female rat. Using double labelling immunohistochemistry, we mapped the
      distribution of nNOS-, OT- and AVP-immunoreactive (IR) neuronal cell bodies in
      the different parts of the PVN. About 80% of nNOS-IR cell bodies were
      magnocellular. About 30% of the nNOS-IR cell bodies were OT-IR, colocalization
      being most frequent in the rostral parts. In comparison, only approximately 3% of
      all nNOS-IR cell bodies were AVP-IR, evenly distributed throughout the PVN. True
      Blue (TB), administered unilaterally into the spinal cord, disclosed that most
      spinally projecting cell bodies in the PVN were localized in caudal parts.
      Combined TB tracing and nNOS immunohistochemistry showed that approximately 30%
      of spinally projecting neurons in the PVN were nNOS-IR, and that approximately
      40% of these were magnocellular. Ipsilateral nNOS spinal projections were about
      eight times more frequent than the contralateral nNOS projections. The study
      describes the detailed neuroanatomical organization of nNOS neurons coexpressing
      OT or AVP, and of nNOS spinally projecting neurons within defined parts of the
      PVN. In contrast to the paraventriculo-spinal system in general, we show that the
      nNOS paraventriculo-spinal pathway to a large extent originates in magnocellular
      cell bodies. The results suggest that NO is an important messenger in the
      paraventriculo-spinal pathway that may in part act in concert with OT.

PMID- 11457428
TI  - Reinnervation of a denervated skeletal muscle by spinal axons regenerating
      through a collagen channel directly implanted into the rat spinal cord.
AB  - In the present study, the continuity between the central nervous system (CNS) and
      the peripheral nervous system (PNS) was restored by mean of a collagen channel in
      order to reinnervate a skeletal muscle. Three groups of animals were considered.
      In the first group, one end of the collagen channel was implanted in the cervical
      spinal cord of adult rats. The other end was connected to a 30-mm autologous
      peripheral nerve graft (PNG) implanted into the denervated biceps brachii muscle.
      The gap between the spinal cord and the proximal nerve stump varied from 3 to 7
      mm. In the second group of animals, the distal end of the PNG graft was ligatured
      in order to compare the survival of the growing axons in the presence and in the
      absence of a muscular target. In the third group of animals, the extraspinal
      stump of the collagen channel was ligatured. Our study demonstrates that spinal
      neurons and dorsal root ganglion (DRG) neurons can grow long axons through the
      collagen channel over a 7-mm gap and reinnervate a denervated skeletal muscle.
      The results also indicate that the presence of a PNG at the extraspinal stump of
      the collagen channel is essential for axonal regrowth and that the muscle target
      contributes to the long-term maintenance of the regenerating axons. These data
      might be interesting for clinical application when the continuity between the CNS
      and PNS is interrupted such as in root avulsion.

PMID- 11457429
TI  - Induced mitochondrial failure in the feline brain: implications for understanding
      acute post-traumatic metabolic events.
AB  - OBJECTIVE: Recently, evidence has become available implicating mitochondrial
      failure as a crucial factor in the pathogenesis of acute brain damage following
      severe traumatic brain injury (TBI). However, it remains unclear how
      mitochondrial dysfunction affects cerebral metabolism. Therefore the aim of the
      study was to evaluate the impact of 'isolated' mitochondrial failure on local
      cerebral metabolism. METHODS: Cerebral mitochondrial metabolism was blocked by
      local microdialysis perfusion with cyanide in seven cats. Local brain tissue
      oxygen tension (p(tiO(2))), carbon dioxide tension (p(tiCO(2))) and pH, as well
      as extracellular cerebral fluid, glucose, lactate, pyruvate and glutamate were
      monitored, using a Neurotrend sensor and microdialysis, respectively. Tissue
      oxygen consumption was measured in a microrespirometric system, and
      ultrastructural changes evaluated via electron microscopy. RESULTS: Brain tissue
      oxygen tension increased from a baseline of 31+/-9 mmHg to 84+/-30 mmHg after 60
      min of cyanide perfusion (P<0.05), concomitant a decrease in oxygen consumption
      from 14.45+/-3.91 microl/h/mg to 10.83+/-1.74 microl/h/mg (P<0.05). Brain tissue
      pH was decreased after 60 min of cyanide perfusion (6.83+/-0.16) compared to
      baseline (7.07+/-0.39) (P<0.05), whereas p(tiCO(2)) did not show significant
      changes. Lactate massively increased from a baseline of 599+/-270 micromol/l to
      2609+/-1188 micromol/l immediately after cyanide perfusion (P<0.05). The
      lactate:glucose ratio increased from 0.79+/-0.15 before cyanide perfusion to
      6.40+/-1.44 at 40 min after cyanide perfusion (P<0.05), while no significant
      changes in the lactate:pyruvate ratio could be observed. Glutamate increased from
      a baseline of 11.6+/-7.2 micromol/l to 61.4+/-44.7 micromol/l after cyanide
      perfusion (P<0.05). CONCLUSION: The results of this study show that 'isolated'
      cerebral mitochondrial failure initiates changes in cerebral substrates and
      biochemistry, which are very similar to most of the changes seen after severe
      human head injury, except for the early fall in p(tiO(2)), further indicating a
      crucial involvement of mitochondrial impairment in the development of brain
      damage after TBI.

PMID- 11457430
TI  - Neuroprotective effects of an adenoviral vector expressing the glucose
      transporter: a detailed description of the mediating cellular events.
AB  - Considerable knowledge exists concerning the events mediating neuron death
      following a necrotic insult; prompted by this, there have now been successful
      attempts to use gene therapy approaches to protect neurons from such necrotic
      injury. In many such studies, however, it is not clear what sequence of cellular
      events connects the overexpression of the transgene with the enhanced survival.
      We do so, exploring the effects of overexpressing the Glut-1 glucose transporter
      with an adenoviral vector in hippocampal cultures challenged with the excitotoxin
      kainic acid (KA). Such overexpression enhanced glucose transport, attenuated the
      decline in ATP concentrations, decreased the release of excitatory amino acid
      neurotransmitters, and decreased the total free cytosolic calcium load.
      Commensurate with these salutary effects, neuronal survival was enhanced with
      this gene therapy intervention. Thus, the neuroprotective effects of this
      particular gene therapy occurs within the known framework of the mechanisms of
      necrotic neuronal injury.

PMID- 11457431
TI  - Intrinsic excitability changes in vestibular nucleus neurons after unilateral
      deafferentation.
AB  - Two synergistic plastic mechanisms have recently been identified in rat medial
      vestibular nucleus (MVN) neurons during 'vestibular compensation', the behavioral
      recovery that follows damage to the vestibular receptors or nerve of one inner
      ear. Ipsi-lesional MVN neurons develop a significant increase in their intrinsic
      excitability, and a marked decrease in the functional efficacy of GABA(A) and
      GABA(B) receptors, within 4 h of unilateral vestibular deafferentation. These
      mechanisms presumably counteract the disfacilitation and excessive commissural
      inhibition of the ipsi-lesional cells after deafferentation, and thus promote the
      recovery of resting activity. In this study, we investigated the intrinsic
      membrane properties and spike firing characteristics of rostral ipsi-lesional MVN
      neurons in slices from animals that underwent vestibular compensation for either
      24-72 h or 7-10 days. Significant changes were observed in the spontaneous in
      vitro discharge rate, resting membrane potentials and voltage-activated membrane
      conductances of type B cells, but not type A cells. There was a significant
      increase in the number of type B(LTS) cells compared to normal. These findings
      indicate that during vestibular compensation marked changes occur in ion channel
      expression and function selectively in type B MVN neurons. These changes are
      appropriate to increase the responsiveness of type B cells both to their own
      intrinsic pacemaker-like membrane conductances and excitatory synaptic inputs.
      Together with the downregulation of inhibitory receptor efficacy, this increased
      intrinsic excitability may be sufficient to restore the resting discharge of the
      deafferented neurons in vivo. These results therefore provide further evidence
      for synaptic and neuronal plasticity in ipsi-lesional MVN neurons during
      vestibular compensation.

PMID- 11457432
TI  - CB1 receptor mediated analgesia from the Nucleus Reticularis Gigantocellularis
      pars alpha is activated in an animal model of neuropathic pain.
AB  - Cannabinoids are known to suppress responses to noxious stimulation in animals
      and man. Recent research has suggested a role for endogenous cannabinoids in the
      descending inhibition of dorsal horn cells via a supraspinal site of action. We
      have recently demonstrated [J. Physiol. 506(2) (1998) 459] that the nucleus
      reticularis gigantocellularis pars alpha (GiA) is a major source of such
      descending modulation, and importantly, that this system is activated in response
      to noxious stimulation. We have therefore investigated the role of CB1 receptor
      activation in mediating the antinociceptive effects of activation of GiA in
      models of acute and chronic pain. Microinjections (0.5 microl 60% DMSO) of either
      WIN 55,212-2 (5 microg, selective CB1 agonist), SR141716A (50 microg, competitive
      CB1 antagonist), both compounds together, or vehicle alone into GiA were
      performed prior to these tests in a randomised, blind manner. In control animals,
      WIN 55,212-2 markedly increased withdrawal latencies in the tail flick test and
      reduced responses to subcutaneous formalin. These effects were blocked by co
      administration of SR141716A. These data suggest that activation of cannabinoid
      CB1 receptor subtypes in GiA leads to behavioural analgesia. In animals with
      partial sciatic nerve ligation, microinjection of drugs and injection of formalin
      were performed contralaterally to the site of ligation. Partial sciatic nerve
      ligation significantly reduced behavioural responses to contralaterally applied
      formalin. Microinjection of SR141716A to GiA reversed this inhibition of
      responses to formalin in animals with partial sciatic nerve ligation. These data
      provide evidence that endogenous CB1 receptor ligands are involved in GiA
      mediated antinociception, and that this system is important for the modulation of
      nociceptive transmission in an animal model of chronic neuropathic pain.

PMID- 11457433
TI  - Neuronal network analysis based on arrival times of active-sleep specific
      inhibitory postsynaptic potentials in spinal cord motoneurons of the cat.
AB  - The neuronal network responsible for motoneuron inhibition and loss of muscle
      tone during active (REM) sleep can be activated by the injection of the
      cholinergic agonist carbachol into a circumscribed region of the brainstem
      reticular formation. In the present report, we studied the arrival times of
      inhibitory postsynaptic potentials (IPSPs) observed in intracellular recordings
      from cat spinal cord motoneurons. These recordings were obtained during episodes
      of motor inhibition induced by carbachol or during motor inhibition associated
      with naturally occurring active sleep. When the observed IPSP arrival times were
      analyzed as a superposition of renewal processes occurring in a pool of pre-motor
      inhibitory interneurons, it was possible to estimate the following parameters:
      (1) the number of independent sources of the IPSPs; (2) the rate at which each
      source was bombarded with excitatory postsynaptic potentials (EPSPs); and (3) the
      number of EPSPs required to bring each source to threshold. From the data based
      upon the preceding parameters and the unusually large amplitudes of the active
      sleep-specific IPSPs, we suggest that each source is a cluster of synchronously
      discharging pre-motor inhibitory interneurons. The analysis of IPSP arrival times
      as a superposition of renewal processes, therefore, provides quantitative
      information regarding neuronal activity that is as far as two synapses upstream
      from the site of the recording electrode. Consequently, we suggest that a study
      of the temporal evolution of these parameters could provide a basis for dynamic
      analyses of this neuronal network and, in the future, for other neuronal networks
      as well.

PMID- 11457434
TI  - Conditioned fear stimuli reinstate cocaine-induced conditioned place preference.
AB  - These studies examined the ability of a conditioned stimulus previously paired
      with footshock to reinstate cocaine-induced conditioned place preference. Male
      rats were given either odor or tone in a paired (PRD group) or explicitly
      unpaired (random, RND group) manner with footshock. All rats were subsequently
      trained in a cocaine conditioned place preference (CPP) task. Cocaine CPP was
      demonstrated in all groups. After CPP extinction, presentation of the conditioned
      fear stimulus produced a greater degree of reinstatement in PRD rats compared to
      the RND group. This was true whether the conditioned stimulus was odor or tone,
      but when odor was used as the conditioned stimulus, the RND group also partially
      reinstated cocaine CPP. In rats trained with tone as the conditioned stimulus,
      presentation of the tone during the test for reinstatement produced robust
      reinstatement of cocaine CPP only in the PRD, but not RND, group. In contrast, a
      subsequent priming injection with cocaine reinstated cocaine CPP equally in both
      RND and PRD groups. These studies indicate for the first time that conditioned
      fear stimuli induce reinstatement of cocaine CPP, and suggest that stimuli
      associated with prior stress may produce relapse in humans.

PMID- 11457435
TI  - Multiple ligand interaction of alpha-synuclein produced various forms of protein
      aggregates in the presence of Abeta25-35, copper, and eosin.
AB  - Various protein aggregates of alpha-synuclein developed by way of the common
      protein self-oligomerization in the presence of Abeta25-35, copper, and eosin
      were examined. All the aggregates exhibited congo red birefringence although the
      actual amounts of the aggregates were varied as determined by thioflavin T
      binding fluorescence. When their morphologies were analyzed in relation to in
      vitro cytotoxicity, the smallest granular aggregates obtained with copper
      exhibited the highest cytotoxicity, while the fibrous structures by eosin did not
      affect the cell.

PMID- 11457436
TI  - The role of glutamate and vasopressin in the excitation of RVL neurones by
      paraventricular neurones.
AB  - Neurones in the paraventricular nucleus of the hypothalamus project to rostral
      ventrolateral medullary spinally projecting vasomotor neurones. We studied the
      excitatory action and the role of glutamate and vasopressin in this pathway in
      anaesthetised rats. A five barrel micropipette assembly was used for
      extracellular recording of neuronal activity and for microiontophoresis of drugs
      into the vicinity of identified medullary vasomotor neurones. Iontophoresis of L
      glutamate or vasopressin into the vicinity of a vasomotor neurone increased
      activity, effects which were blocked by simultaneous iontophoretic application of
      a glutamate receptor antagonist, or a vasopressin V(1a) antagonist respectively.
      Paraventricular neurones were activated either by microinjecting D,L-homocysteic
      acid or by disinhibition by microinjecting bicuculline. The excitatory effects on
      vasomotor neurones, of paraventricular nucleus stimulation at some sites were
      prevented by simultaneous microiontophoretic application of kynurenic acid or at
      other sites by application of V(1a) antagonist. Neither antagonist altered the
      ongoing activity of the vasomotor neurones. Therefore, glutamate or vasopressin
      may act as excitatory neurotransmitters at synapses of paraventricular neurones
      on rostral ventrolateral medullary vasomotor neurones.

PMID- 11457439
TI  - Structural and thermal characterization of dioctadecyldimethylammonium bromide
      dispersions by spin labels.
AB  - Dioctadecyldimethylammonium bromide (DODAB) dispersions obtained by simply mixing
      the amphiphile in water, and by bath-sonication, were investigated by electron
      spin resonance (ESR) of stearic acids and their methyl ester derivatives, labeled
      at the 5th and 16th carbons of the acyl chain. The ESR spectra indicate that the
      non-sonicated dispersions are formed mainly by one population of DODAB vesicles,
      either in the gel (T<T(m)) or in the liquid-crystalline (T>T(m)) state. Around
      T(m) there is a co-existence of the two phases, with a thermal hysteresis of
      about 3.2 degrees C. In sonicated DODAB dispersions, spin labels indicate two
      different environments even for temperatures far below T(m): one similar to that
      obtained with non-sonicated samples, a gel phase, and another one in the liquid
      crystalline state. The fluid phase domain present below T(m) could correspond to
      either the periphery of bilayer fragments, reported to be present in sonicated
      DODAB dispersions, or to high curvature vesicles.

PMID- 11457440
TI  - Lipolytic activity of porcine pancreas lipase on fatty acid esters of
      dialkylglycerols: a structural basis for the design of new substrates for the
      assay of pancreatic lipases activity.
AB  - For the design of new synthetic substrates for the assay of pancreatic lipases
      activity, acyl dialkylglycerols of variable chain length were prepared.
      Titrimetric assay of these substrates showed the highest lipolytic activity of
      porcine pancreas lipase (pPL) with butanoyl dibutylglycerol. The activity is
      lower but comparable to that shown by pPL towards the classical substrate
      tributyrin. The 4-nitrophenylcarbonate of 1,2-di-O-butylglycerol, has been
      prepared and proposed as synthetic substrate for a new spectrophotometric assay
      of pancreatic lipases.

PMID- 11457441
TI  - The total syntheses of D-erythro-sphingosine, N-palmitoylsphingosine (ceramide),
      and glucosylceramide (cerebroside) via an azidosphingosine analog.
AB  - The total synthesis of D-erythro-sphingosine (9) was performed by a chirospecific
      method starting from D-galactose via an azidosphingosine intermediate to give
      highly homogeneous (>99.9% C18:1) sphingosine base (9) which contained no
      observable olefin isomerization by product and was demonstrated to be optically
      pure by a novel method utilizing Mosher's acid. Ceramide (10) was prepared from
      this sphingosine (9) with highly homogeneous (99.8% C16:0) palmitic acid by two
      methods. The cerebroside glucosylceramide (23) was the next sphingolipid in this
      series to be synthesized in a highly homogeneous form. These three sphingolipids
      are currently being used for biophysical studies of the structures of their
      hydrated bio-molecular assemblies.

PMID- 11457442
TI  - The physical properties of glycosyl diacylglycerols. Calorimetric, X-ray
      diffraction and Fourier transform spectroscopic studies of a homologous series of
      1,2-di-O-acyl-3-O-(beta-D-galactopyranosyl)-sn-glycerols.
AB  - We have synthesized a homologous series of saturated 1,2-di-O-n-acyl-3-O-(beta-D
      galactopyranosyl)-sn-glycerols with odd- and even-numbered hydrocarbon chains
      ranging in length from 10 to 20 carbon atoms, and have investigated their
      physical properties using differential scanning calorimetry (DSC), X-ray
      diffraction (XRD) and Fourier-transform infrared (FTIR) spectroscopy. The DSC
      results show a complex pattern of phase behaviour, which in a typical preheated
      sample consists of a lower temperature, moderately energetic lamellar
      gel/lamellar liquid-crystalline (L(beta)/L(alpha)) phase transition and a higher
      temperature, weakly energetic lamellar/nonlamellar phase transition. On annealing
      at a suitable temperature below the L(beta)/L(alpha) phase transition, the
      L(beta) phase converts to a lamellar crystalline (L(c1)) phase which may undergo
      a highly energetic L(c1)/L(alpha) or L(c1)/inverted hexagonal (H(II)) phase
      transition at very high temperatures on subsequent heating or convert to a second
      L(c2) phase in certain long chain compounds on storage at or below 4 degrees C.
      The transition temperatures and phase assignments for these galactolipids are
      supported by our XRD and FTIR spectroscopic measurements. The phase transition
      temperatures of all of these events are higher than those of the comparable phase
      transitions exhibited by the corresponding diacyl alpha- and beta-D-glucosyl
      glycerols. In contrast, the L(beta)/L(alpha) and lamellar/nonlamellar phase
      transition temperatures of the beta-D-galactosyl glycerols are lower than those
      of the corresponding diacyl phosphatidylethanolamines (PEs) and these glycolipids
      form inverted cubic phases at temperatures between the lamellar and H(II) phase
      regions. Our FTIR measurements indicate that in the L(beta) phase, the
      hydrocarbon chains form a hexagonally packed structure in which the headgroup and
      interfacial region are undergoing rapid motion, whereas the L(c) phase consists
      of a more highly ordered, hydrogen-bonded phase, in which the chains are packed
      in an orthorhombic subcell similar to that reported for the diacyl-beta-D
      glucosyl-sn-glycerols. A comparison of the DSC data presented here with our
      earlier studies of other diacyl glycolipids shows that the rate of conversion
      from the L(beta) to the L(c) phase in the beta-D-galactosyl glycerols is slightly
      faster than that seen in the alpha-D-glucosyl glycerols and much faster than that
      seen in the corresponding beta-D-glucosyl glycerols. The similarities between the
      FTIR spectra and the first-order spacings for the lamellar phases in both the
      beta-D-glucosyl and galactosyl glycerols suggest that the headgroup orientations
      may be similar in both beta-anomers in all of their lamellar phases. Thus, the
      differences in their L(beta)/L(c) conversion kinetics and the
      lamellar/nonlamellar phase properties of these lipids probably arise from subtly
      different hydration and H-bonding interactions in the headgroup and interfacial
      regions of these phases. In the latter case, such differences would be expected
      to alter the ability of the polar headgroup to counterbalance the volume of the
      hydrocarbon chains. This perspective is discussed in the context of the mechanism
      for the L(alpha)/H(II) phase transition which we recently proposed, based on our
      X-ray diffraction measurements of a series of PEs.

PMID- 11457443
TI  - Membrane interactions of a new class of anticancer agents derived from
      arylchloroethylurea: a FTIR spectroscopic study.
AB  - We have investigated the interaction between a new class of antineoplastic agents
      derived from arylchloroethylurea (CEU) and different lipids such as
      dimyristoylphosphatidylcholine (DMPC) in the absence and presence of 30 mol% of
      cholesterol, dimyristoylphosphatidylglycerol (DMPG) and a mixture made of 1
      palmitoyl-2-oleylphosphatidylcholine (POPC) and DMPC by Fourier transform
      infrared (FTIR) spectroscopy. The results indicate that the drugs incorporate in
      the bilayer and cause a decrease of the phase transition temperature and an
      increase of the conformational disorder of the lipid acyl chains. These effects
      are dependent on the nature (degree of branching, length of the alkyl chain and
      presence of a sulfur atom), as well as on the position of the R substituent and
      are related to the cytotoxicity of the drugs. More specifically, the more
      cytotoxic drugs, such as 4-sec-butyl CEU, are those having a bulky branched
      substituent and those for which the disordering effect on the lipid bilayer is
      the greatest. On the other hand, the disordering effect is small for the long
      chain CEUs, such as 4-n-hexadecyl CEU, which have been shown to have weak
      cytotoxic activity.

PMID- 11457444
TI  - Packing characteristics of a model system mimicking cytoplasmic bacterial
      membranes.
AB  - The phase diagram of fully hydrated mixtures of
      dipalmitoylphosphatidylethanolamine and -phosphatidylglycerol was constructed and
      the coexistence lines of the solidus and liquidus curve calculated based on
      regular solution theory using two nonideality parameters for each of the phase to
      account for nonideal and nonsymmetric mixing. Both lipids show nonideal
      miscibility in the liquid-crystalline phase, while a region of immiscibility
      exists in the lamellar-gel phase between the mole fraction x(DPPE)=0.05-0.4. Two
      lines of three-phase coexistence around 35 and 40 degrees C reflects the presence
      of lipid domains predominantly composed of phosphatidylglycerol as well as of the
      mixed lipid system. This is reflected in the positive nonideality parameters of
      the gel phase obtained from the simulation of the phase diagram. Moreover,
      segregation of pure phosphatidylethanolamine domains was detected in mixtures
      x(DPPE)>0.9, which formed multilamellar liposomes, while unilamellarity was
      observed for the mixed lipid systems owing to the presence of the negatively
      charged phosphatidylglycerol. The packing constraints of these phospholipids,
      major components of cytoplasmic bacterial membranes, may be of importance in the
      interaction with various solutes like antimicrobial peptides, and were explained
      based on the nature of the headgroups and the molecular geometry of the
      phospholipids.

PMID- 11457446
TI  - YidC/Oxa1p/Alb3: evolutionarily conserved mediators of membrane protein assembly.
AB  - This review focuses on a novel, evolutionarily conserved mediator of membrane
      protein assembly in bacteria, mitochondria and chloroplasts. This factor is
      designated YidC in Escherichia coli, and is localized in the inner membrane. YidC
      is homologous to Oxa1p in the mitochondrial inner membrane and Alb3 in the
      chloroplast thylakoid membrane, but does not seem to have a homologue in the
      endoplasmic reticulum membrane. It has been suggested that YidC operates both as
      a separate unit and in connection with the SecYEG-translocon depending on the
      substrate membrane protein that is integrated into the membrane. Mitochondria do
      not possess a SecYEG-like complex and Oxa1p is thought to form, or to contribute
      to the formation of, a novel translocon in the mitochondrial inner membrane. Alb3
      in the chloroplast thylakoid membrane is, just like YidC and Oxa1p, involved in
      membrane protein assembly, but only few details are known.

PMID- 11457447
TI  - Protein translocation machineries of peroxisomes.
AB  - Targeting of peroxisomal matrix and membrane proteins is performed by distinct
      transport machineries and requires the concerted action of at least 23 peroxins.
      Cargo recognition takes place in the cytosol and the multiple binding sites for
      peroxisomal signal sequence receptors at the peroxisomal membrane reflect the
      existence of an import cascade where the cargo-loaded receptors successively
      interact with different components of the import machinery. These interactions
      are likely to trigger conformational changes of the proteins within the import
      cascade which are required for the consecutive steps of peroxisomal protein
      import: docking, translocation, cargo release and receptor recycling.

PMID- 11457448
TI  - Evolutionary relationship of Rickettsiae and mitochondria.
AB  - Phylogenetic data support an origin of mitochondria from the alpha
      proteobacterial order Rickettsiales. This high-rank taxon comprises exceptionally
      obligate intracellular endosymbionts of eukaryotic cells, and includes family
      Rickettsiaceae and a group of microorganisms termed Rickettsia-like endosymbionts
      (RLEs). Most detailed phylogenetic analyses of small subunit rRNA and chaperonin
      60 sequences consistently show the RLEs to have emerged before Rickettsiaceae and
      mitochondria sister clades. These data suggest that the origin of mitochondria
      and Rickettsiae has been preceded by the long-term mutualistic relationship of an
      intracellular bacterium with a pro-eukaryote, in which an invader has lost many
      dispensable genes, yet evolved carrier proteins to exchange respiration-derived
      ATP for host metabolites as envisaged in classic endosymbiont theory.

PMID- 11457449
TI  - Synthetic peptides as inactivators of multimeric enzymes: inhibition of
      Plasmodium falciparum triosephosphate isomerase by interface peptides.
AB  - Synthetic peptides corresponding to two distinct segments of the subunit
      interface of the homodimeric enzyme triosephosphate isomerase (residues 9-18,
      ANWKCNGTLE, peptide I; residues 68-79, KFGNGSYTGEVS, peptide II) from Plasmodium
      falciparum (PfTIM) have been investigated for their ability to act as inhibitors
      by interfering with the quaternary structure of the enzyme. An analog of peptide
      II containing cysteine at the site corresponding to position 74 and tyrosine at
      position 69 in the protein sequence KYGNGSCTGEVS (peptide III) was also
      investigated. A substantial fall in enzyme activity was observed following
      incubation of the enzyme with peptide II, whereas peptide I did not show any
      appreciable inhibition. The inhibitory effect was more pronounced on two mutants
      of PfTIM (Y74C and Y74G), both of which have reduced stability compared to the
      wild-type protein due to an interface cavity. The IC50 value determined for
      peptide II is in the range of 0.6-0.8 microM. This study suggests that interface
      peptides of oligomeric enzymes can be used to inhibit dimeric enzymes by
      disrupting their native multimeric states and may provide lead structures for
      potential inhibitor design.

PMID- 11457450
TI  - 15-Deoxy-delta12,14-PGJ2, but not troglitazone, modulates IL-1beta effects in
      human chondrocytes by inhibiting NF-kappaB and AP-1 activation pathways.
AB  - The activation of peroxisome proliferator-activated receptor gamma (PPARgamma)
      has been shown to inhibit the production and the effects of proinflammatory
      cytokines. Since interleukin-1beta (IL-1beta) directly mediates cartilage
      degradation in osteoarthritis, we investigated the capability of PPARgamma
      ligands to modulate IL-1beta effects on human chondrocytes. RT-PCR and Western
      blot analysis revealed that PPARgamma expression was decreased by IL-1beta. 15
      deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), in contrast to troglitazone, was
      highly potent to counteract IL-1beta-induced cyclooxygenase-2 and inductible
      nitric oxide synthase expression, NO production and the decrease in proteoglycan
      synthesis. Western blot and gel-shift analyses demonstrated that 15d-PGJ2
      inhibited NF-kappaB activation, while troglitazone was ineffective. Although 15d
      PGJ2 attenuated activator protein-1 binding on the DNA, it potentiated c-jun
      migration in the nucleus. The absence or the low effect of troglitazone suggests
      that 15d-PGJ2 action in human chondrocytes is mainly PPARgamma-independent.

PMID- 11457451
TI  - A new class of scorpion toxin binding sites related to an A-type K+ channel:
      pharmacological characterization and localization in rat brain.
AB  - A new scorpion toxin (3751.8 Da) was isolated from the Buthus martensi venom,
      sequenced and chemically synthesized (sBmTX3). The A-type current of striatum
      neurons in culture completely disappeared when 1 microM sBmTX3 was applied (Kd=54
      nM), whereas the sustained K+ current was unaffected. 125I-sBmTX3 specifically
      bound to rat brain synaptosomes (maximum binding=14 fmol x mg(-1) of protein,
      Kd=0.21 nM). A panel of toxins yet described as specific ligands for K+ channels
      were unable to compete with 125I-sBmTX3. A high density of 125I-sBmTX3 binding
      sites was found in the striatum, hippocampus, superior colliculus, and cerebellum
      in the adult rat brain.

PMID- 11457452
TI  - Furin and membrane type-1 metalloproteinase mRNA levels and activation of
      metalloproteinase-2 are associated with arterial remodeling.
AB  - Matrix metalloproteinase (MMP) activation is an essential feature of pathological
      and physiological arterial enlargement or shrinkage. Recently, furin-activated
      membrane type-1 MMP (MT1-MMP) was identified as the in vivo activator of MMP2 in
      mice. Although arterial enlargement and shrinkage are important in several
      pathological processes, this proprotein convertase-MT1-MMP axis has not been
      described during arterial remodeling. In rabbit femoral and carotid arteries, we
      report an increase in furin and MT1-MMP mRNA levels before and at the onset of
      arterial remodeling followed by an increase in activated MMP2. This reveals the
      presence of the proprotein convertase-MT1-MMP axis in flow-induced arterial
      remodeling and identifies furin as a possible target for local intervention in
      pathological arterial remodeling.

PMID- 11457453
TI  - Ceruloplasmin as low-density lipoprotein oxidase: activation by ascorbate and
      dehydroascorbate.
AB  - The ability of ceruloplasmin (Cp) to oxidize low-density lipoproteins (LDL) in
      the presence of water-soluble antioxidants was investigated and a reaction
      mechanism proposed. Ascorbate strongly enhanced LDL oxidation, but only after its
      rapid consumption. Dehydroascorbate enhanced Cp-mediated LDL oxidation even more
      strongly. Lipid-soluble antioxidants and water-soluble peroxides did not show
      noticeable activation. However, loading of LDL with lipid hydroperoxides
      increased the initial oxidation rate. We conclude that Cp mediates a localized
      redox cycle, where reduction of Cp-Cu2+ is effected by water-soluble reductants
      and reoxidation by liposoluble hydroperoxides.

PMID- 11457454
TI  - Expression of ARF6 mutants in neuroendocrine cells suggests a role for ARF6 in
      synaptic vesicle biogenesis.
AB  - ARF6 regulates membrane trafficking between the plasma membrane and endosomes. We
      investigated the role of ARF6 in synaptic vesicle biogenesis as this process
      occurs both at the plasma membrane and at endosomes. We used a synaptic vesicle
      marker protein, p-selectin-horseradish peroxidase (HRP), to follow the effects of
      ARF6 expression on synaptic vesicle biogenesis in PC12 neuroendocrine cells.
      Expression of a constitutively active ARF6 mutant increased, while expression of
      a nucleotide-free ARF6 mutant decreased, p-selectin-HRP levels in the synaptic
      vesicle peak. These results provide the first direct evidence for a role for ARF6
      in synaptic vesicle biogenesis.

PMID- 11457455
TI  - Sequence analyses and comparative modeling of fly and worm fibroblast growth
      factor receptors indicate that the determinants for FGF and heparin binding are
      retained in evolution.
AB  - The presence of a large number of fibroblast growth factors (FGFs) and multiple
      splice forms of their receptors (FGFRs) in higher vertebrates makes the three
      dimensional (3D) analysis of FGF interactions with their receptors a formidable
      task. The situation differs in Caenorhabditis elegans (worm) and Drosophila
      melanogaster (fruit fly), where only one or two FGF and FGFR sequences have been
      identified. Structural studies of the FGF-FGFR complexes in such primitive
      organisms should reveal the basic features of the ligand-receptor interactions as
      they first emerged through evolution. We have analysed the sequences of worm and
      fly FGFs and FGFRs and used the recently determined crystal structure of the
      human FGF1-FGFR2-heparin ternary complex [Pellegrini, L., Burke, D.F., von Delft,
      F., Mulloy, B. and Blundell, T.L. (2000) Nature 407, 1029-34] to construct 3D
      models of the homologous complexes. In spite of a low sequence similarity with
      their human counterparts, key structural features required for ligand-receptor
      and protein-heparin binding in humans are conserved in the fly and worm FGF-FGFR
      heparin complexes. Analyses of the models show that tertiary interactions that
      are not conserved in sequence are maintained through novel interactions or
      complementary mutations in the fly and worm sequences. The overall charge
      distributions observed in the human FGF-FGFR-heparin complex are retained in the
      fly and worm models. The arginine residue at position 253 in the linker region
      between the Ig-like domains D2 and D3 in the wild type fly and worm sequences is
      particularly striking, as the Pro253Arg mutation in humans is responsible for
      Apert syndrome. This change may enhance the affinity of receptors for their FGF
      molecules as observed in Apert mutants.

PMID- 11457456
TI  - Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti
      topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60
      cells.
AB  - Salvicine is a novel diterpenoid quinone derivative possessing strong antitumor
      activities and was demonstrated to stabilize the DNA topoisomerase II (Topo II)
      cleavage complex in vitro and in vivo. In the present work we investigated the
      possible mechanism through which disturbance of Topo II by salvicine led to cell
      death. We found that salvicine induced DNA strand breaks in human promyelocytic
      leukemia HL-60 cells and DNA damage correlated with cell growth inhibition. DNA
      damage induced by brief exposure to salvicine could be partially reversed, but
      early DNA breaks triggered the process of apoptosis. Preferential damage in the
      P2 promoter region of the oncogene c-myc was detected, whereas no obvious DNA
      damage was found in the 3' region of the same gene. Furthermore, the expression
      of some protooncogenes such as c-myc, c-fos and c-jun was examined, showing that
      salvicine produced a reduction in the transcription rate of c-myc in a dose
      dependent manner and a marked induction of c-fos and c-jun expression was
      observed. It appears possible that DNA damage within such genomic regions is an
      early event, which could lead to growth inhibition mediated by alterations of the
      expression of selected proliferation regulatory genes, such as c-myc, c-fos and c
      jun, and ultimately cell death.

PMID- 11457457
TI  - Chloroplast TatC plays a direct role in thylakoid (Delta)pH-dependent protein
      transport.
AB  - The thylakoid (Delta)pH-dependent pathway transports folded proteins. Identified
      components include Hcf106 and Tha4. Orthologs of these proteins plus a membrane
      protein called TatC are essential for the homologous bacterial Tat system. Here
      we report identification of a chloroplast TatC (cpTatC). cpTatC is an integral
      thylakoid membrane protein as determined by in vitro chloroplast import and
      immunoblotting. Antibody to cpTatC specifically inhibited the thylakoid (Delta)pH
      dependent pathway in vitro. cpTatC is present in about the same quantity as
      estimated translocation sites, whereas Hcf106 and Tha4 are present in 5-8-fold
      excess. These results are relevant to mechanistic models for this system.

PMID- 11457458
TI  - Activation of Raf-1 is defective in annexin 6 overexpressing Chinese hamster
      ovary cells.
AB  - Annexin 6 is a Ca2+-dependent phospholipid-binding protein involved in membrane
      trafficking. In this study we demonstrate the association of Raf-1 with
      recombinant rat annexin 6. Raf-annexin 6 interaction was shown to be independent
      of cell activation by epidermal growth factor (EGF) or phorbol esters (12-O
      tetradecanoyl-phorbol-13-acetate (TPA)). A stable Chinese hamster ovary (CHO)
      anx6 cell line overexpressing annexin 6 was established to examine the function
      of annexin 6. In these cells, no increase of Ras-GTP levels, induced by EGF or
      TPA, was detected. In addition, the activity of Raf was completely inhibited,
      whereas the mitogen-activated protein kinase-P was unaffected.

PMID- 11457459
TI  - Increased expression of mitochondrial transcription factor A and nuclear
      respiratory factor-1 in skeletal muscle from aged human subjects.
AB  - The expression of two factors involved in the nuclear-mitochondrial crosstalk,
      namely the mitochondrial transcription factor A (TFAM) and the nuclear
      respiratory factor-1 (NRF-1), was studied in human skeletal muscle biopsies of
      young and aged subjects. Aged subjects presented a 2.6-fold and an 11-fold
      increase of the levels of TFAM protein and TFAM mRNA, respectively. The increased
      expression of TFAM was associated to the doubling of NRF-1 DNA-binding affinity
      and to a 6-fold increase of NRF-1 mRNA level. The upregulation of TFAM and NRF-1,
      in aged skeletal muscle, appears involved in the pathway leading to the age
      related increase of mitochondrial DNA content.

PMID- 11457460
TI  - Apaf-1 localization is modulated indirectly by Bcl-2 expression.
AB  - Apoptotic protease activating factor-1 (Apaf-1) is an adaptor molecule essential
      for caspase-9 activation. Subcellular analysis of Apaf-1 in NIH-3T3 fibroblasts
      and the immature murine B cell lymphoma WEHI-231 indicates that Apaf-1 is
      localized in the Golgi apparatus and cytoplasm. Bcl-2 overexpression in WEHI-231
      cells disrupts Apaf-1 localization in Golgi, causing a perinuclear Apaf-1
      redistribution. Bcl-2 overexpression in NIH-3T3 fibroblasts however does not
      cause similar Apaf-1 redistribution, suggesting that cell type factors are
      involved in the redistribution process. The ability of Bcl-2 to modify Apaf-1
      subcellular localization is not explained by direct interaction between Apaf-1
      and Bcl-2. These data may help to clarify the anti-apoptotic Bcl-2 function.

PMID- 11457461
TI  - Genistein, a soy isoflavone, is a potent alpha-glucosidase inhibitor.
AB  - Genistein is an isoflavone that is known to be contained in soybean. It was
      proved that genistein plays a pivotal role in homeostasis in the human body. In
      the course of screening for useful alpha-glucosidase inhibitors, we isolated and
      identified genistein as a candidate for alpha-glucosidase inhibitor from
      fermentation broths of a Streptomyces sp. Genistein was shown to be a reversible,
      slow-binding, non-competitive inhibitor of yeast alpha-glucosidase with a K(i)
      value of 5.7x10(-8) M when the enzyme mixture was pretreated with genistein.
      These results show a possibility that genistein could be a useful tool for
      metabolic disorders.

PMID- 11457462
TI  - Influence of the conformational flexibility on the kinetics and dimerisation
      process of two Candida rugosa lipase isoenzymes.
AB  - We have investigated the interfacial activation process of two isoenzymes from
      Candida rugosa (Lip1 and Lip3) using triacetin as substrate. Kinetics were
      coupled to inhibition experiments in order to analyse the transition between the
      open and closed conformers. This process was slow, particularly for Lip1, in the
      absence of an interface provided by the substrate or a detergent. Dimers of Lip3
      were also purified and their catalytic action was closer to that of a typical
      esterase. In spite of the high sequence homology between Lip1 and Lip3, small
      changes enhance hydrophobicity in the binding pocket of Lip3 and increase the
      flexibility of its flap. We postulated that these factors account for the higher
      tendency of Lip3 to dimerise fixing its open conformation.

PMID- 11457463
TI  - Visualizing detergent resistant domains in model membranes with atomic force
      microscopy.
AB  - Evidence is accumulating that in cell membranes microdomains exist, also referred
      to as rafts or detergent resistant membranes. In this study, atomic force
      microscopy is used to study supported lipid bilayers, consisting of a fluid
      phosphatidylcholine, sphingomyelin and cholesterol. Domains were visualized of
      which the morphology and size depended on the cholesterol concentration. The
      presence of cholesterol was found to induce bilayer coupling. At 30 mol%
      cholesterol, a change in percolation phase was observed, and at 50 mol%, when
      both fluid lipids and solid lipids are saturated with cholesterol, phase
      separation was still observed. In addition, we were able to directly visualize
      the resistance of domains against non-ionic detergent.

PMID- 11457465
TI  - Antiplatelet and anticoagulant effects of "HN-11 500," a selective thromboxane
      receptor antagonist.
AB  - The antiplatelet and anticoagulant effect of a thromboxane receptor (TX receptor)
      antagonist developed by Nycomed (Linz) has been studied in a placebo-controlled
      double-blind phase I study. Sixteen healthy male volunteers received different
      single oral doses of "HN-11 500" (C(14)H(15)NO(5)S(2); 1, 10, 100, 200, and 400
      mg). Eight volunteers received placebo. The washout period between each dosage
      applied was at least 12 days. Platelet aggregation induced by the thromboxane
      mimetic "U 46 619" (C(21)H(34)0(4)) and platelet adhesion to siliconized glass
      were significantly and dose-dependently inhibited. The effect lasted between 3
      and 4 h (10 mg) and 8 h (400 mg), respectively, and correlated well with the
      pharmacokinetic data. Platelet aggregation seems to be more sensitive to monitor
      the effects of HN-11 500 on platelet function than platelet adhesion. Plasma
      levels of 300 ng/ml HN-11 500 probably leads to >90% inhibition of platelet
      aggregation. The template bleeding time slightly increased but did not exceed the
      normal range. Furthermore, there was a wide variation of results. There were no
      significant changes in platelet counts, platelet-induced thrombin generation time
      (PITT), and blood coagulation parameters. All doses of HN-11 500 were well
      tolerated. HN-11 500 is a potent TX receptor antagonist (TXRA), which inhibits
      either platelet aggregation or platelet adhesion, which has not yet been
      described. In clinical routine, TXRAs have to demonstrate the effectiveness in
      large clinical trials for different clinical indications and to compete with
      single or combined administrations of cyclooxygenase (COX) inhibitors,
      thienovridines, thromboxane synthase inhibitors, and GIIb/IIIa inhibitors.

PMID- 11457466
TI  - Interaction of fibrinolysis and prothrombotic risk factors in neonates, infants
      and children with and without thromboembolism and underlying cardiac disease. a
      prospective study.
AB  - To evaluate the role of plasminogen activator inhibitor-1 (PAI-1) and tissue-type
      plasminogen activator (t-PA) in children with an estimated risk of vascular
      occlusion reported to range from 7% to 16%, we conducted a prospective study in
      infants and children with underlying cardiac disease. One hundred and twenty-five
      children (neonate - 16 years) were investigated. In 9 infants out of the 125
      children vascular occlusion occurred, closely related to cardiac catheterisation
      and arterial or venous lines during major cardiac surgery. Six of the nine
      neonates and infants with (n=6) and without (n=3) prothrombotic risk factors
      showed evidence of a basically impaired fibrinolytic system. Five of the nine
      infants showed increased PAI-1 clearly correlated to the 4G/4G genotype of the
      plasminogen activator-1 promoter polymorphism along with elevated t-PA
      concentration before the first diagnostic cardiac catheterisation was performed.
      One infant presented with increased t-PA concentration only. Five of the six
      children with reduced fibrinolytic capacity had further prothrombotic risk
      factors. CONCLUSION: Data of this study indicate that neonates and infants with
      underlying cardiac disease and basically increased PAI-1 due to the 4G/4G variant
      of the PAI-1 promoter polymorphism along with elevated t-PA levels in combination
      with further prothrombotic risk factors are at high risk of developing early
      thromboembolism during cardiac catheterisation.

PMID- 11457467
TI  - PAI-I 4G/5G polymorphism and sudden cardiac death in patients with coronary
      artery disease.
AB  - The 4G/5G polymorphism of the plasminogen activator inhibitor type I (PAI-I) gene
      is involved in coronary artery disease (CAD), with the highest risk in 4G/4G
      homozygotes. The role of PAI-I polymorphism in patients suffering from CAD and
      history of sudden cardiac death (SCD) has not been addressed yet. We studied the
      frequency distribution of the PAI-I gene to test the hypothesis that the 4G/4G
      genotype favors myocardial ischemia and, even in the absence of acute infarction,
      promotes SCD in patients with CAD. METHODS: The PAI-I 4G/5G genotypes and PAI-I
      antigen plasma levels were determined in 97 patients with CAD and a history of
      SCD treated with an implantable cardioverter defibrillator (ICD) (defibrillator
      group) comparing to 113 patients with CAD but no history of SCD (control group).
      RESULTS: The defibrillator group consisted of significantly more 4G/4G
      homozygotes and higher PAI-I levels than the control group (44% vs. 24%, 173+/-41
      vs. 144+/-49 ng/ml; P<.01). The carriers of 4G allele had a significantly higher
      risk for SCD (odds ratio (OR) 1.9) with the highest risk in the 4G/4G genotype
      (OR 3.6, P<.01). CONCLUSION: These results suggest that the PAI-I 4G/4G genotype
      is associated with SCD in patients suffering from CAD.

PMID- 11457468
TI  - Mutations in the genes regulating methylene tetrahydrofolate reductase (MTHFR C-
      >T677) and cystathione beta-synthase (CBS G-->A919, CBS T-->c833) are not
      associated with myocardial infarction in African Americans.
AB  - Moderate hyperhomocysteinemia is a putative risk factor for cardiovascular
      disease. Molecular studies have demonstrated increased plasma homocysteine levels
      in the presence of DNA mutations in either the methylenetetrahydrofolate
      reductase (MTHFR) enzyme found in the remethylation pathway or the enzyme
      cystathione beta-synthase (CBS) of the transsulfuration pathway. To determine
      whether the mutation C-->T677 in the MTHFR gene or the T-->C833/844ins68 and G-
      >A919 mutations in the CBS gene are associated with myocardial infarction (MI) in
      African Americans, DNA was analyzed from samples obtained from a case-control
      study conducted at a large, inner-city hospital. One-hundred ten African American
      subjects with a diagnosis of MI and 185 race- and age-matched controls were
      recruited. Our results demonstrated that 15% of the MI cases were heterozygous
      for the C-->T677 (MTHFR) mutation, while 1.8% were homozygous. When compared to
      the controls in which 15% were heterozygous and 2.1% were homozygous, no
      significant association with MI was observed. In addition, 34% of the cases were
      heterozygous for the T-->C833 (CBS) mutation while 6% were homozygous. This is
      compared to 32% and 5% of the controls having the heterozygous and homozygous
      genotype, respectively. No significant association was observed for the T-->C833
      (CBS) mutation among the cases and controls. Although this mutation has no
      significant association with MI, the prevalence of the heterozygous state was
      higher than what has been reported for whites (12%). No mutations for G-->A919
      (CBS) were detected in the cases or controls. The racial differences of the CBS T
      ->C833 polymorphism suggest that further investigation into the other areas of
      the CBS gene is needed.

PMID- 11457469
TI  - Apo A-I binding to platelets detected by flow cytometry.
AB  - Lipoprotein-platelet interactions are very important in atherosclerosis and
      thrombosis. Several studies have been carried out on specific binding of various
      lipoproteins to platelets. But there is considerable disagreement about the
      details of these binding sites. Although low-density lipoprotein (LDL) receptors
      of several cells have been studied extensively, there is little datum about high
      density lipoprotein (HDL) receptors. Apolipoprotein (apo) A-I may play a major
      role in the determination of the specificity of HDL receptors. In this study,
      binding of apo A-I to platelets was investigated by using a flow cytometric
      method. Citrated blood samples were obtained from five healthy and seven
      hypercholesterolemic subjects. Apo A-I antibody was incubated with the citrated
      whole blood before and after activation with ADP or thrombin receptor agonist
      peptide (TRAP). Then fluorescein isothiocyanate (FITC)-labeled secondary
      antibodies were added and analyzed on a Becton-Dickinson FACSort flow cytometer.
      In the hypercholesterolemic group, apo A-I binding to platelets was found to be
      significantly decreased after activation with TRAP (P<.05), but not after
      activation with ADP. In the control group, after platelet activation with ADP or
      TRAP, the apo A-I MFI values were not found to be significantly different from
      the values of resting platelets (P>.05). In this study, we demonstrated that apo
      A-I can bind to platelets, and this supports the hypothesis that apo A-I may play
      a major role in HDL binding to platelets.

PMID- 11457470
TI  - Variability in platelet responses to collagen--comparison between whole blood
      perfusions, traditional platelet function tests and PFA-100.
AB  - The purpose of this study was to determine if the results obtained in platelet
      function tests and whole blood perfusions are associated with those in platelet
      function analyser (PFA)-100. We used collagen type I monomers and fibrils to
      analyse the distinct roles of glycoprotein (GP) Ia/IIa and other collagen
      receptors in flowing blood under a high shear rate (1600/s) and in aggregation
      studies. Also, anticoagulation [citrate vs. D-phenylalanyl-1-prolyl-1 arginine
      chloromethyl ketone (PPACK)] was varied to enhance the functions of GP Ia/IIa,
      since it has been shown that the cation-poor environment of citrated blood
      impairs GP Ia/IIa-dependent platelet recruitment. Large interindividual
      variability (45-fold) was detected in deposition of platelets in whole blood
      perfusions over collagen monomers, whereas this variation was only fourfold in
      fibrils. In PFA, this variation was reduced to 2.5-fold. However, platelet
      deposition on monomers is associated with epinephrine-enhanced PFA (r=-.49,
      P<.03), whereas platelet deposition on fibrils is correlated with adenosine
      diphosphate (ADP)-enhanced PFA (r=-.47, P<.05), suggesting a distinct synergism
      between epinephrine and monomers (GP Ia/IIa) as well as ADP with fibrils (other
      collagen receptors). Donors with 807 C/C polymorphism of GP Ia (n=14) had longer
      lag phase in aggregation experiments compared with C/T (n=7) both by monomers and
      fibrils (P<.04), but these polymorphisms with their mild impact on GP Ia/IIa
      activity did not markedly differ in other tests. In conclusion, the results
      obtained in perfusion studies and PFA experiments correlated, but PFA fails to
      reveal the large-scale variability related to collagen-induced platelet
      responses.

PMID- 11457471
TI  - Increased expression and localization of a serine protease inhibitor, protease
      nexin-1 (PN-1), in the ovary and uterus during implantation in rat.
AB  - Protease nexin-1 (PN-1) is a serine protease inhibitor (serpin) that inactivates
      several proteases, including thrombin, urokinase, plasminogen activators (PA),
      and plasmin. It also plays a role in regulating proteolytic activity generated by
      PA system. PN-1 is known to be involved in tissue remodeling, cellular
      invasiveness, matrix degradation, and tumor growth. However, the role of PN-1 in
      female reproductive tracts, such as the uterus, ovary, and oviduct, during
      pregnancy is not known. The present study was designed to investigate the changes
      of PN-1 mRNA level and localization in the tracts during implantation and early
      pregnancy by using reverse transcription (RT)-polymerase chain reaction (PCR) and
      in situ hybridization. We found that PN-1 mRNA levels were coordinately regulated
      during early pregnancy in a stage- and tissue-specific manner, such that an
      increased expression of PN-1 gene appeared at the time of the implantation period
      in the uterus and ovary. Both the uterus and ovary synthesized PN-1 mRNA and
      their maximal PN-1 expression occurred on Day 6.5 postcoitum (p.c.). On 13.5 days
      of pregnancy, PN-1 level was low in the uterus and ovary. On the other hand, PN-1
      mRNA in the oviduct did not show after 6.5 days of pregnancy. It appears that PN
      1 mRNA in the uterus and ovary was highly regulated during early pregnancy, which
      might have an important role in implantation of rat blastocysts. PN-1 was
      localized in endometrial stromal cells of the uterus and in granulosa cells of
      the unstimulated primary follicles in the ovary during periimplantation period.
      Also, PN-1 mRNA expression was higher at implantation period than that at
      nonimplantation period of pregnancy. In conclusion, PN-1 is expressed in female
      reproductive tracts and highly regulated during implantation and early pregnancy.

PMID- 11457472
TI  - Activation of caspase-3/caspase-3-like activity in rat cardiomyocytes by an RGD
      peptide, but not the GPIIb/IIIa antagonist lotrafiban.

PMID- 11457473
TI  - The generation of superoxide anion in blood platelets in response to different
      forms of Proteus mirabilis lipopolysaccharide: effects of staurosporin,
      wortmannin, and indomethacin.
AB  - Lipopolysaccharide (LPS), the major component of the outer membrane of Gram
      negative bacteria may activate blood platelets. The aim of our study was to
      evaluate the effects of different forms of Proteus mirabilis LPS and isolated
      lipid A and polysaccharide part on the production of superoxide radicals in blood
      platelets and to estimate the role staurosporin, wortmannin and indomethacin on
      this process. We compared the generation of superoxide radicals in platelets
      treated with LPS after preincubation with inhibitors of the signal transduction
      pathways, namely staurosporin (inhibitor of protein kinase C), wortmannin
      (inhibitor of phosphoinositide 3-kinase), and indomethacin (inhibitor of
      cycloxygenase). Our results demonstrate that all LPS molecules and their
      fragments caused a stimulation of O2- generation in platelets (P<.5). LPSS1959
      had the strongest stimulatory effect. Straurosporin and wortmannin, but not
      indomethacin inhibited O2- production in LPS-stimulated platelets. Staurosporin
      (8 nM) and wortmannin (50 nM) caused about 50% inhibition of thrombin-induced O2-
      generation in platelets, while indomethacin (10 microM) had only a slight
      inhibitory effect on this process. Our results provide support that in LPS- and
      thrombin-activated platelets, at least part of O2- generation in platelets, while
      indomethacin (10 microM) had only a slight inhibitory effect on this process. Our
      results provide support that in LPS- and thrombin-activated platelets, at least
      part of O2- is generated due to the activation of the enzymes (protein kinase C
      and phosphoinositide 3-kinase) involved in signal transduction pathway.
      Cycloxygenase seems to be not involved in this process.

PMID- 11457474
TI  - Endogenous release of tissue factor pathway inhibitor by topical application of
      an ointment containing mucopolysaccharide polysulfate to nonhuman primates.
AB  - Several studies have shown that tissue factor pathway inhibitor (TFPI) is
      released after the intravenous and subcutaneous administration of heparin and
      heparin-related drugs. Mucopolysaccharide polysulfate (MPS) is a preparation of
      glycosaminoglycans (GAGS) derived from mammalian cartilage, which has several
      structural and functional properties similar to heparin. Previous reports have
      shown that MPS is capable of releasing TFPI after intravenous administration.
      Therefore, this investigation was performed to determine the ability of topically
      administered MPS to release TFPI in a nonhuman primate model. A group of four
      monkeys were administered 3% MPS ointment in a dosage of 0.5 g/kg corresponding
      to 15 mg MPS/kg; another four monkeys were administered placebo ointment at a
      dosage of 0.5 g/kg once a day for 5 days in a period of 10 days. No effect of MPS
      was observed on the coagulation assays activated partial thromboplastin time
      (APTT), thrombin time (TT) and Heptest or on the platelet count. However, both
      the total and free TFPI levels were significantly and progressively elevated over
      the 10-day period in comparison to the placebo control group (P<.05). It is
      proposed that the ability of the topically administered MPS to increase the free
      and total TFPI levels may be one of the modes of action that contributes to the
      anticoagulant and anti-inflammatory actions of this agent.

PMID- 11457475
TI  - Opsonization of yeast cells with equine iC3b, C3b, and IgG.
AB  - The main opsonins in serum are antibodies and complement factor C3. The
      opsonization mechanisms including complement activation and deposition are
      important in studies of phagocytosis and of mechanisms of microbial immune
      evasion. The objective of the present study was to monitor the deposition of
      complement C3 and IgG from equine serum on yeast cells (Saccharomyces cerevisiae)
      using a flow cytometric immunoassay. Correlations were made between the opsonic
      coating and phagocytic capacity using equine blood neutrophils. In addition, the
      bound C3 fragments were characterized by SDS-PAGE and Western blot analyses.
      Opsonic coating of yeast with equine C3 and IgG occurred rapidly with detectable
      levels with as little as 0.75% serum. C3 deposition was a result of complement
      activation and no passive adsorption was observed. When complement was
      inactivated, the fluorescence indicating IgG deposition increased 3-6-fold,
      indicating spatial competition between C3 and IgG at binding. Opsonization with
      1.5% serum led to suboptimal equine neutrophil phagocytosis of yeast cells which
      was dependent on complement activation by the classical pathway. With > or =6.25%
      serum, IgG contributed to opsonization and phagocytosis. With 50% serum and more,
      C3 was deposited also by the alternative pathway. Phagocytosis rates became
      optimal with 3% serum, and did not increase further with higher serum
      concentrations. The main form of C3 on the yeast cells was iC3b and the rest was
      C3b without any detectable breakdown products (C3c or C3dg). The equine
      complement components are similar in size to the human equivalents. It may be
      concluded that opsonization of yeast particles leading to phagocytosis, occurs at
      very low serum concentrations (1.5%) and that it is dependent on activation of
      the classical complement pathway at this low opsonic level. This is an important
      finding for efficient host defense, e.g. extravascular phagocytosis at infection
      sites.

PMID- 11457476
TI  - Inflammation-induced changes in serum modulate chicken macrophage function.
AB  - Inflammation-induced changes in serum protein profiles and the effects of such
      serum on a chicken macrophage cell line HD11 were studied to find whether the
      changes in serum affect cellular immunity. Four-week-old male broiler chickens
      were injected subcutaneously with either olive oil or 50% croton oil mixed in
      olive oil to induce inflammation. The birds were bled at 48h after injection, and
      serum protein profiles were compared using sodium dodecyl sulfate polyacrylamide
      gel electrophoresis (SDS-PAGE) and densitometric evaluation. At 48h post
      injection the serum from croton oil-injected birds showed distinct changes in
      protein profiles characterized by a selective increase or decrease in levels of
      several serum proteins. The protein bands which showed increases had relative
      molecular weights (Mr) corresponding to 65kilo Daltons (kD), 42kD, and two or
      more proteins with Mr> or =200kD. The levels of serum albumin (49kD), and a 56kD
      protein were reduced in croton oil-injected birds. The modulating effects of such
      serum on HD11 cells were studied using bacterial lipopolysaccharide (LPS) or
      phorbol myristate acetate (PMA) induced functional activation of these cells. The
      LPS-induced interleukin-6 (IL-6) production by HD11 cells was not affected by the
      presence of either olive oil-treated control or croton oil-treated inflammatory
      serum but nitrite production was enhanced by the inflammatory serum. Similarly,
      inflammatory serum also enhanced PMA-induced respiratory burst measured using
      dichlorofluorescein diacetate (DCF-DA) oxidation mediated by reactive oxygen
      intermediates. These results suggest that inflammatory serum can modulate
      macrophage function by influencing the production of reactive oxygen and nitrogen
      species which could affect their phagocytic and bactericidal activities.

PMID- 11457477
TI  - The binding of soybean agglutinin (SBA) to the intestinal epithelium of Atlantic
      salmon, Salmo salar and rainbow trout, Oncorhynchus mykiss, fed high levels of
      soybean meal.
AB  - A lectin present in soya, soybean agglutinin (SBA), was identified in
      electrophoretic profiles and immunoblots of dehulled solvent-extracted soybean
      meal (DSSM), full-fat soybean meal (FFSM) and of aqueous extracts of feeds
      incorporating them in their formulation. A quantitative estimation was made of
      the proportion of SBA comprising the total protein in FFSM and a trial diet was
      prepared containing an amount of pure SBA similar to that in diets incorporating
      high levels of the whole soya product. Fish fed with this diet exhibited similar
      pathological disruption of the intestinal tract to that observed in fish given a
      diet with a high level of DSSM (60% of the diet). Furthermore, immuno
      histochemistry revealed the binding of the SBA to the enterocytes lining the
      intestinal villi both of fish fed a diet incorporating pure SBA and those fed a
      diet containing a high-level of soya (60%). Our results suggest that SBA binds in
      vivo to the intestinal epithelium of fish and has a contributory role in
      pathological changes associated with fish feeds containing high levels of soybean
      proteins.

PMID- 11457478
TI  - Production and characterization of monoclonal antibodies detecting chicken
      interleukin-2 and the development of an antigen capture enzyme-linked
      immunosorbent assay.
AB  - Eleven monoclonal antibodies (mAbs) which are specific for chicken interleukin-2
      (chIL-2) were produced and characterized by enzyme-linked immunosorbent assay
      (ELISA), Western blotting and neutralizing assays. These mAbs were used to
      develop a mAb-based antigen capture ELISA specific for chicken IL-2 detection.
      Anti-IL-2 mAbs bound specifically to E. coli-derived rchIL-2 in ELISA and
      identified a 16kDa IL-2 polypeptide band in Western blot. Several mAbs were shown
      to neutralize the biological activities of both rchIL-2 and native chicken IL-2
      as measured by concanavalin A (ConA)-induced lymphocyte proliferation assay, IL-2
      bioassay, and natural killer cell assay. Among the neutralizing mAbs, the mAb
      chIL-2/11 was most potent in neutralizing IL-2 activity. To develop a sensitive
      ELISA for the detection of chicken IL-2, an antigen capture ELISA was developed
      using the mAb chIL-2/16 as the antigen capture antibody and rabbit anti-IL-2
      peptide antibody as the detection antibody. Using the mAb-based antigen capture
      ELISA, significant correlation between the level of IL-2 detected in bioassays
      and in ELISA was observed. These results showed that the mAb-based antigen
      capture ELISA is less time-consuming and more reliable compared to a conventional
      IL-2 bioassay for chicken IL-2. These neutralizing mAbs will facilitate basic
      immunobiological studies of the role of IL-2 in normal and disease states in
      chickens.

PMID- 11457479
TI  - Cloning and characterization of cDNAs encoding four different canine
      immunoglobulin gamma chains.
AB  - cDNAs encoding four different canine immunoglobulin G (caIgG) gamma chains were
      identified in this study. One of these IgG gamma chain cDNAs, (caIgG-A),
      represents 92.5% of the IgG gamma chain cDNAs in a dog spleen cell cDNA library;
      a second partial IgG gamma chain cDNA (caIgG-B) was also identified in the
      library. The other two IgG gamma chain cDNAs (caIgG-C and caIgG-D) were RT-PCR
      amplified from canine lymphoma samples. Comparison of the four different canine
      IgG gamma chain cDNAs showed homologies from 83.6 to 89.2% and from 73.1 to 81.8%
      at nucleotide and amino acid sequence levels, respectively. Despite the high
      similarity in CH1, CH2 and CH3 domains among the different caIgG gamma chains,
      the hinge regions were distinct, sharing only 19.0-35.2% homology at the amino
      acid level. No multiple duplication of the hinge region, as reported for human
      IgG1 and IgG3, was detected in any of the canine IgG gamma chains. The numbers of
      cysteines in the putative hinge regions were found to be 3, 2, 7 and 3 for the
      four canine IgG heavy gamma chains (A, B, C and D), respectively. Specific
      primers were designed based on caIgG gamma chain hinge region DNA sequences and
      were used in RT-PCR for measuring different caIgG gamma chain mRNA levels in
      canine PBMC samples.

PMID- 11457480
TI  - Subclinical paratuberculosis in goats following experimental infection. An
      immunological and microbiological study.
AB  - An experimental oral infection of goats with a caprine isolate of Mycobacterium
      a. subsp. paratuberculosis was used to investigate immunological and
      bacteriological events during the subclinical phase of infection. Seven goats at
      5-8 weeks of age were given a bacterial suspension in milk-replacement three
      times weekly for 9 weeks. Six animals were kept as controls. Cellular recall
      responses against M. a. paratuberculosis were analysed by means of a lymphocyte
      proliferation test, an IFN-gamma assay and an IL-2 receptor assay. All inoculated
      animals had detectable CMI responses from 9 weeks post-inoculation and through
      the 2 years of study, although the responses were highest during the first year.
      Antibodies against M. a. paratuberculosis could be detected from weeks 15-20 in
      four of the seven animals, and one additional animal became antibody positive at
      week 35, while two inoculated animals did not produce significant antibody titres
      during the experiment. At about 1-year post-inoculation, two animals became
      faecal shedders, while two others started to excrete bacteria into faeces about 2
      years post-inoculation. The appearance of M. a. paratuberculosis in faeces was
      not associated with a decline in cellular responses as far as could be assessed
      using the current methods for measuring CMI. Pathological lesions due to M. a.
      paratuberculosis infection and presence of bacteria were recorded in the
      intestine and/or mesenteric lymph nodes of five animals while lymph node changes
      suggestive of paratuberculosis were observed in one animal. Only the two animals
      with no signs of an active infection at necropsy showed a considerable decline in
      the cellular parameters during the last year of the study, particularly in the
      IFN-gamma assay. The two animals with the highest levels of M. a.
      paratuberculosis responsive CD8+ lymphocytes in the circulation about 1-year post
      inoculation had no detectable lesions in the distal ileum and colon at necropsy,
      while high numbers of gammadelta T-cells responsive to M. a. paratuberculosis in
      the circulation were associated with disseminated lesions in the distal ileum and
      colon.

PMID- 11457481
TI  - Determination of the oxidative burst chemiluminescent response of avian and
      murine-derived macrophages versus corresponding cell lines in relation to
      stimulation with Salmonella serotypes.
AB  - In contrast to mammalian systems, avian species lack a resident or harvestable
      macrophage population in the abdominal exudate. Peritoneal macrophages in the
      chicken can be elicited if an inflammatory agent such as sephadex is injected.
      This study examines the kinetics of different macrophage populations, derived by
      different methods of isolation and from different hosts, with respect to the
      elicited oxidative burst upon infection with host-adapted Salmonella serotypes.
      The nature of the oxidative burst elicited by murine and avian-derived and cell
      line macrophages was determined after stimulation with phorbol myristate (PMA),
      zymosan A, and Salmonella serotypes. Both murine and chicken peritoneal
      macrophages, chicken blood monocytes and corresponding cell lines, J774A.1 and HD
      11, were unable to produce a detectable chemiluminescent (CL) response after
      interaction with Salmonella using the luminescent probe luminol. However, both
      PMA and zymosan A induced a CL response in all cell types, with PMA eliciting a
      higher and earlier peak response (pkH) than zymosan A. Lucigenin-enhanced CL in
      both murine and chicken macrophages was achieved with PMA, zymosan A and
      Salmonella serotypes. In this case, zymosan A induced higher responses than PMA.
      In the peritoneal macrophages of both hosts, there were no significant
      differences in the oxidative burst induced by the different Salmonella serotypes.
      However, the J774A.1 (murine) cells demonstrated significant differences, with S.
      enterica serotype Choleraesuis (S. choleraesuis and S. gallinarum producing the
      highest response. In the HD-11 (chicken) cells, S. choleraesuis and S. dublin
      elicited the higher CL. With both cell lines, S. abortusovis failed to induce an
      appreciable CL response. In these experiments it was demonstrated that oxidative
      burst was not detectable in monocytes/macrophage populations using luminol, which
      suggests a link to the lack of a myeloperoxidase system in these cells. Lucigenin
      enhanced CL appeared independent from the myeloperoxidase system, indicating
      production of another oxidative species compared with luminol. No discernable
      effect of host specificity with regard to Salmonella serotype and respective host
      was seen in host-derived or cell line macrophages, and cell line macrophages
      displayed altered functional characteristics with regard to oxidative burst in
      comparison with their primary counterparts.

PMID- 11457482
TI  - Localization of cyclooxygenase isozymes in cardiovascular tissues of dogs treated
      with naproxen.
AB  - Prostaglandins have diverse roles in the cardiovascular system mediating both
      physiologic and inflammatory responses. Two cyclooxygenase isoforms,
      cyclooxygenase-1 and cyclooxygenase-2, catalyze prostaglandin production. In many
      tissues and cell types studied, cyclooxygenase-1 is constitutively active whereas
      cyclooxygenase-2 expression is primarily responsible for prostaglandin production
      during inflammation. However, little information exists concerning which isoform
      is responsible for prostaglandin-mediated effects in the heart. We examined
      cyclooxygenase-1 and cyclooxygenase-2 expression in heart and vascular tissue of
      dogs using isoform-specific antibodies. In addition, tissues from dogs treated
      with naproxen (5-10mg/kg/day), an inhibitor of prostaglandin production were also
      examined. Cyclooxygenase-1 expression was evident in endothelial cells of the
      microvasculature of the heart, aorta and renal artery. Cyclooxygenase-1
      expression was also found in fibrocytes of the tricuspid valve and in the chordae
      tendinae. Animals treated with naproxen exhibited a similar pattern and intensity
      of cyclooxygenase-1 staining. No cyclooxygenase-2 expression was evident in
      cardiac tissue. However, minimal cyclooxygenase-2 immunoreactivity was present in
      the vascular endothelial cells of small myocardial blood vessels located in
      several regions of the heart as well as in endothelial cells of the aorta. These
      data may expand our understanding of the effects of non-steroidal anti
      inflammatory drugs on cardiac function.

PMID- 11457483
TI  - p65 Homodimer activity in distal airway cells determines lung dysfunction in
      equine heaves.
AB  - Nuclear factor-kappaB (NF-kappaB) activity, which is a key regulator of
      inflammatory gene expression, is increased in bronchial epithelial cells from
      horses suffering from heaves (a hypersensitivity-associated inflammatory
      condition of the lung). To determine whether this increased activity extends to
      distal airways and to other pulmonary cells, cells recovered by broncho-alveolar
      lavage (BAL) in healthy and heaves-affected horses were assessed for NF-kappaB
      activity. NF-kappaB activity was much higher in BAL cells from heaves-affected
      horses, especially during crisis (disease exacerbation), than in cells from
      healthy horses. Moreover, the level of NF-kappaB activity found in BAL cells was
      positively correlated to total lung resistance and to the proportion of
      neutrophils present in BAL fluid. Finally, prototypical p65-p50 NF-kappaB
      heterodimers were absent from BAL cells, which mostly contained p65 homodimers.
      These results (1) show that increased NF-kappaB activity is a general feature of
      heaves lung; (2) demonstrate the importance of p65 homodimers in neutrophilic
      inflammation; and (3) suggest that the use of specific NF-kappaB inhibitors could
      improve lung function in heaves-affected horses.

PMID- 11457484
TI  - Eye-drop DNA can induce IgA in the tears and bile of chickens.
AB  - DNA vaccines protect chickens against lethal virus infections but whether they
      induce local antibody which is associated with preventing viral entry, is
      unknown. We were able to show how avian DNA vaccines can induce local IgA. 65
      microg plasmid DNA encoding the reporter protein beta-galactosidase induced
      antigen-specific IgA in the tears of 6/10 birds, IgA in the bile of 4/10 birds
      and IgG in the serum of 2/10 birds. Giving the DNA by the intramuscular route, as
      is more usual, induced lacrimal IgA in 2/8 birds, biliary IgA in no birds and
      serum IgG in 4/8 birds. Eye-drop DNA therefore favoured local IgA whereas
      intramuscular DNA favoured serum IgG. Further to this preliminary work eye-drop
      DNA should be improved by adjuvants and cytokines as a way of inducing protective
      IgA at the mucosal surfaces of the alimentary and respiratory tracts.

PMID- 11457485
TI  - Development and characterization of monoclonal antibodies against canine trypsin.
AB  - Canine cationic trypsin was purified by salting-out, gel filtration and affinity
      chromatography. Purity was confirmed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). The molecular weight was ca. 28kDa by SDS-PAGE.
      Thirty hybridomas were obtained which produced mAb to canine cationic trypsin by
      the cell fusion technique. Twenty-two of these recognized cationic trypsin only,
      while eight hybridomas recognized both cationic and anionic trypsin. Several of
      the anti-canine cationic trypsin mAb were purified by salting-out and DEAE ion
      change chromatography using ascites fluid of immunized BALB/c mice. The mAb
      proved to have very high specificity to canine cationic trypsin as shown by
      immunoblotting and it may be possible to use them to develop clinical assays.

PMID- 11457486
TI  - Homologues of natural killer cell receptors NKG2-D and NKR-P1 expressed in
      cattle.
AB  - Partial transcripts of the homologues in cattle, of the genes encoding the NKR-P1
      and NKG2-D natural killer cell lectin-like receptor families, were cloned by
      reverse transcriptase-PCR from bovine spleen. Three different cDNAs were
      partially sequenced for the NKG2-D homologue, and two for the NKR-P1 homologue.
      Identity to human nucleotide sequences was of 90 and 75%, respectively, and all
      structural residues of C-type lectin carbohydrate recognition domains were
      conserved. The identification of two of its members allows to hypothesise the
      existence of a bovine NK gene complex, prospectively located on chromosome 5.

PMID- 11457487
TI  - Electroconvulsive shock exposure prevents neuronal apoptosis after kainic acid
      evoked status epilepticus.
AB  - In the aftermath of prolonged continuous seizure activity (status epilepticus,
      SE), neuronal cell death occurs in the brain regions through which the seizure
      propagates. The vulnerability to adrenalectomy-induced apoptotic neuronal death
      was recently reported to be reduced by prior exposure to repeated daily
      noninjurious electroconvulsive shock (ECS). The present studies identified
      apoptosis and apoptosis-associated gene products in the neurodegenerative
      response to experimentally controlled periods (1 or 2 h) of SE in the rat, and
      determined whether exposure to ECS can interrupt these apoptotic responses
      mechanisms. Internucleosomal DNA fragmentation and the presence of apoptotic-like
      neurons (as assessed by in situ double labeling technique) was detected in
      hippocampus and rhinal cortex at 24 h after SE. Under these conditions, levels of
      both mRNA and protein encoded by the 'death promoting' bcl-XS gene were increased
      in the same brain areas. Pretreatment of animals for 7 days with low intensity
      (minimal) ECS conferred resistance to SE-evoked neurodegeneration, as assessed
      histopathologically by silver staining. Associated with this neuroprotective
      action was a reduction in the incidence of apoptosis-like neuronal morphology and
      DNA fragmentation, and a prevention of the increase in Bcl-XS protein and mRNA in
      hippocampus and rhinal cortex. These data suggest that pre-exposure to
      controlled, brief noninjurious seizures decreases vulnerability to programmed
      neuronal cell death, that this neuroprotective action occurs upstream from Bcl
      XS, and that increases in bcl-XS gene expression may serve as a sensitive
      indicator of neurodegeneration following SE.

PMID- 11457488
TI  - Estrogen receptor beta (ERbeta) mRNA and protein in serotonin neurons of
      macaques.
AB  - This study used double in situ hybridization (ISH) to examine the colocalization
      of estrogen receptor beta (ERbeta) mRNA in serotonin neurons of rhesus macaques
      (Macaca mulatta). In addition, immunocytochemistry (ICC) was used to examine the
      expression and regulation of ERbeta protein in raphe neurons of the macaque
      midbrain. For double ISH, monkey specific riboprobes for ERbeta incorporating
      radiolabeled-UTP and a riboprobe for the human serotonin reuptake transporter
      (SERT) incorporating digoxigenin were applied to midbrain sections from spayed
      rhesus macaques. ERbeta mRNA hybridization signal was expressed in most cells
      containing SERT mRNA in the dorsal and median raphe and pons. There were also non
      SERT neurons expressing ERbeta mRNA. In addition, ERbeta protein was detected
      with an affinity purified polyclonal antibody generated against a synthetic
      peptide corresponding to the D domain of human ERbeta conjugated to bovine serum
      albumin (provided by Dr. Philippa Saunders, MRC, Edinburgh). Midbrain sections
      containing the dorsal raphe from spayed rhesus macaques with and without hormone
      replacement therapy were processed for ERbeta immunostaining. ERbeta protein was
      detected at a similar intensity and in a similar number of cells in the dorsal
      raphe neurons in all treatment groups. Thus, the expression of ERbeta protein in
      the dorsal raphe was consistent with the expression of ERbeta mRNA. In
      conclusion, ERbeta mRNA is expressed by serotonin neurons and it is translated to
      protein. ERbeta protein, like ERbeta mRNA, is detected at similar levels in the
      presence or absence of ovarian hormones.

PMID- 11457489
TI  - Molecular analysis of estrogen induction of preproenkephalin gene expression and
      its modulation by thyroid hormones.
AB  - Estrogen receptors (ER) and thyroid hormone receptors (TR) are ligand-dependent
      nuclear transcription factors. Estrogen-induced preproenkephalin (PPE) gene
      expression in the hypothalamus is directly related to estrogen-induced lordosis
      behavior in the rat. In the present study, we showed that the PPE mRNA level in
      the ventromedial hypothalamus of female rats was significantly decreased by
      ovariectomy. This decrease was reversed by estrogen replacement in a dose- and
      time-dependent manner. Using transient transfection and electrophoretic mobility
      shift assays (EMSA), functional estrogen response elements (ERE) were identified
      between -437 and -145 base pairs (bp) of the rat PPE gene promoter region. Two
      ERE-like elements are present between -405 and -364 of the rat PPE gene promoter,
      which bind ERalpha as demonstrated by EMSA. Estrogen produced a dose-dependent
      increase in CAT activity in cotransfection assays with ERalpha expression vector
      and a 437PPE-CAT reporter construct containing 437 bp of the rat PPE gene
      promoter and the CAT reporter gene. This estrogen-induced PPE promoter activity
      was inhibited by liganded-TR in transient cotransfection assays. Analysis of DNA
      protein interactions by EMSA revealed that both ERalpha and TR (alpha1 and beta1)
      could bind to the EREs in the rat PPE gene promoter. Furthermore, estrogen
      induction of PPE mRNA in the ventromedial hypothalamus of the ovariectomized
      female rat was significantly attenuated by concomitant administration of
      triiodothyronine. These results suggest that estrogen regulation of the
      hypothalamic PPE gene expression is mediated through an estrogen-receptor complex
      directly interacting with the functional EREs in its promoter region; and that
      this estrogen effect can be modified by thyroid hormones.

PMID- 11457490
TI  - Characterization of apoptosis-genes associated with NMDA mediated cell death in
      the adult rat retina.
AB  - Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing
      signal (CaMKII-alphaB) is altered in retinal neurons exposed to N-methyl-D
      aspartate (NMDA). AIP (myristoylated autocamtide-2-related inhibitory peptide), a
      specific inhibitor of CaMKII provides neuroprotection against NMDA-mediated
      neurotoxicity. In this study, gene-arrays were used to investigate which
      apoptosis-associated genes are altered after exposure to NMDA. The data indicate
      an increased expression (2-7-fold) of five such genes encoding proteins that
      could be involved in NMDA induced cell death. The up-regulated genes are: FasL;
      GADD45; GADD153; Nur77 and TNF-R1. Treatment with AIP blocked their altered
      expression. The results suggest that multiples genes are involved in NMDA-induced
      excitotoxicity and that AIP, a specific inhibitor for CaMKII, regulates the
      expression of these apoptosis-associated genes in the retina.

PMID- 11457491
TI  - A nuclear location for Ca2+-activated adenylyl cyclases I and III in neurones.
AB  - Calcium/calmodulin-sensitive adenylyl cyclases are increasingly recognised as
      important factors in memory formation and synaptic plasticity. We have examined
      the distributions of adenylyl cyclases types I, III, and VIII within rat primary
      sensory neurons. Immunofluorescence revealed distinct staining for adenylyl
      cyclases type I and III, but not adenylyl cyclase type VIII, within the cell
      nucleus. Western blots suggest that a processed form of adenylyl cyclase type III
      may be found within primary neurons and PC12 cells as a 70-kDa protein. We
      propose that the observed nuclear adenylyl cyclases are soluble forms of the
      cyclases.

PMID- 11457492
TI  - Upregulation of the immediate early gene arc in the brains of rats exposed to
      environmental enrichment: implications for molecular plasticity.
AB  - Exposure to an enriched environment, a procedure that induces plasticity in the
      cerebral cortex, is associated with pronounced morphological changes, including
      higher density of dendritic spines, enlargement of synaptic boutons, and other
      putative correlates of altered neurotransmission. Recently, it has been
      demonstrated that animals reared in an enriched environment setting for 3 weeks
      have less neuronal damage as a result of seizures and have decreased rates of
      spontaneous apoptosis. Even though clear morphological modifications are observed
      in the cerebral cortex of animals exposed to heightened environmental complexity,
      the molecular mechanisms that underlie such modifications are yet to be
      described. In the present work, we investigated the expression of the immediate
      early gene arc in the cortex of animals exposed to an enriched environment.
      Animals were exposed daily, for 1 h, to an enriched environment, for a total
      period of 3 weeks. Brains were processed for in-situ hybridization against arc
      mRNA. We found a marked upregulation of arc mRNA in the cerebral cortex of
      animals exposed to the enriched environment, when compared to undisturbed
      controls, an effect that was most pronounced in cortical layers III and V.
      Animals in an additional control group that were handled for 5 min daily,
      displayed intermediate levels of arc mRNA. Furthermore, arc expression was
      upregulated in the CA1, CA2 and CA3 hippocampal subfields and in the striatum,
      but to a lesser extent in the dentate gyrus of animals exposed to an enriched
      environment, as compared to the two control groups. Our results support the
      association between the upregulation of the immediate early gene arc and
      plasticity-associated anatomical changes in the cerebral cortex of the adult
      mammal.

PMID- 11457493
TI  - Differential responses of human neuroblastoma and glioblastoma to apoptosis.
AB  - Staurosporine, a protein kinase and etoposide, a topoisomerase II inhibitor, are
      known to enhance apoptosis. The differential effects of these agents on T98G
      glioblastoma and SK-N-SH neuroblastoma, cell lines both derived from human
      tumors, have not been determined. We assessed cellular viability, DNA
      fragmentation and laddering, chromatin condensation, and Poly(ADP-ribose)
      polymerase (PARP) cleavage induced by these agents at a series of concentrations
      and times. In addition, to gain an understanding of the mechanism by which these
      agents work, we measured Protein Kinase C (PKC) activity. Staurosporine induced
      significant alterations in all apoptotic parameters tested in both cell lines.
      Etoposide induced apoptotic alterations similar to those caused by staurosporine
      in neuroblastoma but produced no detectable apoptotic changes in glioblastoma
      cells. Etoposide induced membrane but not cytosolic PKC activity in neuroblastoma
      but had no effect on PKC activity in glioblastoma. Our results show that the
      induction of apoptosis is cell type dependent. PKC activity appears to be crucial
      in the initiation of apoptosis.

PMID- 11457494
TI  - Identification of a neurorestrictive suppressor element (NRSE) in the human mu
      opioid receptor gene.
AB  - Analysis of the DNA sequence of the human mu-opioid receptor gene (MOR) revealed
      that a region overlapping the start codon was substantially homologous to a DNA
      element named the neurorestrictive suppressor element (NRSE) or restrictive
      element 1 (RE-1). Transient transfection experiments in the L929 and HEK non
      neural cell lines showed that expression of a MOR promoter/reporter gene
      construct was suppressed in non-neural cell lines by inclusion of this MOR NRSE.
      Expression from a thymidine kinase promoter was also suppressed when the MOR NRSE
      was inserted upstream or downstream of the reporter gene. The MOR NRSE did not
      suppress expression of the reporter gene in neural derived cell lines, IMR-32 and
      Neuro 2a. The transcription factor REST which binds NRSE thereby enacting the
      suppression of transcription, was encoded in a plasmid and co-transfected into
      the IMR-32 cells. The REST co-transfected neuronal derived (IMR-32) cells became
      sensitive to the MOR NRSE mediated suppression of reporter gene expression.
      Electrophoretic mobility shift experiments revealed that oligonucleotides
      containing the MOR NRSE were bound by a factor from nuclear extracts of non
      neural cell lines, HeLa and Jurkat. This binding was specifically competed by
      oligonucleotides containing NRSE sequences previously shown to suppress
      transcription through REST. Thus an NRSE element overlapping the human MOR start
      codon suppresses gene expression in non-neural cell lines and may help direct
      neural tissue specific expression of MOR.

PMID- 11457495
TI  - The 5'-untranslated region of the mouse glial cell line-derived neurotrophic
      factor gene regulates expression at both the transcriptional and translational
      levels.
AB  - We previously cloned mouse glial cell line-derived neurotrophic factor (GDNF)
      cDNA and genomic DNA and found that the mouse gene contains a 1086-bp 5'
      untranslated region (5'-UTR). We investigated the contributions of the 5'-UTR to
      promoter activity and found one positive regulatory region and two negative
      regulatory regions in the 5'-UTR. In the present study, using gel retardation
      assays and mutation analyses, two novel cis-elements that interact with nuclear
      extracts from mouse astrocytes were identified. The first cis-element
      (nucleotides (nt) +70 to +81) enhances promoter activity, whereas the second cis
      element (nt +239 to +247) attenuates promoter activity in a position- and
      orientation-dependent manner. Suppression of gene expression by a third region
      (nt +509 to +580) occurs at the translational level. The ATG sequence (nt +547 to
      +549) has the potential to initiate translation and to attenuate the efficiency
      of translation for the GDNF precursor coding region. Furthermore, we identified
      an alternative promoter in the 5'-UTR that is driven by an Sp1 element,
      circumventing the translational suppression. Taken together, the 5'-UTR of mouse
      GDNF contains two novel cis-elements, a short upstream open reading frame and an
      alternative promoter that influences gene expression at both the transcriptional
      and translational levels.

PMID- 11457496
TI  - Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers
      apoptosis in neuronal cells.
AB  - Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the
      processes of peripheral tissue remodeling and fibrinolysis through the regulation
      of plasminogen activation. We found that cultured human astrocytes efficiently
      released PAI-1, and that both mRNA expression and protein release of PAI-1 were
      suppressed by pretreatment of the cells with daunorubicin. To examine the role of
      PAI-1 in the nervous system, neuronally differentiated PC-12 cells (PC-12
      neurons) were maintained in a PAI-1-deficient culture medium derived from
      daunorubicin-pretreated astrocytes. The deficiency of PAI-1 in the medium caused
      a significant reduction in Bcl-2 and Bcl-XL mRNAs and an increase in Bcl-XS and
      Bax mRNAs in PC-12 neurons at 3 h. The changes in balance between mRNA
      expressions of the anti- and pro-apoptotic Bcl-2 family proteins caused caspase-3
      activation following the release of cytochrome c from mitochondria. Apoptotic
      morphological change and DNA fragmentation were also observed in the neuronal
      cells at 24 h. Addition of exogenous PAI-1 protein to the inhibitor-deficient
      medium blocked the apoptotic changes in PC-12 neurons. However, addition of PAI-1
      antibodies to control medium caused similar apoptotic changes in PC-12 neurons.
      During the apoptotic processes, plasminogen activator (PA) activity in the PAI-1
      deficient medium was as low as the control level. The present data suggest that
      PAI-1 has physiological functions other than its role as PA inhibitor for the
      survival of neurons.

PMID- 11457497
TI  - Melatonin receptor RNA is expressed in photoreceptors and displays a diurnal
      rhythm in Xenopus retina.
AB  - Melatonin is an output signal of an endogenous circadian clock of retinal
      photoreceptors, with highest levels occurring at night. Melatonin synthesized in
      the retina appears to act as a paracrine signal by binding to specific receptors
      in the eye. We have previously demonstrated that RNA encoding the Mel(1b) and
      Mel(1c) melatonin receptor subtypes is expressed in the Xenopus laevis retina.
      The goal of this study was to determine the distribution of the Mel(1b) and
      Mel(1c) receptor subtype RNA expression in the retina, and to determine if the
      level of expression of these receptors exhibits a diurnal rhythm. Sections of
      frog neural retina were analyzed by in situ hybridization with 35S-labeled
      Xenopus Mel(1c) and Mel(1b) riboprobes. Hybridization was present in cells of the
      inner nuclear layer and the ganglion cell layer. Moreover, there was
      hybridization in the photoreceptors, which has not been previously reported. To
      test the hypothesis that retinal melatonin receptor mRNA undergoes a diurnal
      rhythm of expression, total RNA was isolated from frog neural retinas obtained at
      3-h intervals during a 24-h period. The total RNA was used in real-time PCR
      assays to quantify the differences in Mel(1b) and Mel(1c) receptor mRNA
      expression at various circadian times. Both the Mel(1b) and Mel(1c) receptor RNA
      demonstrated a diurnal rhythm of expression, with peak levels occurring late in
      the light period, and lowest levels late in the dark period. These results
      support the hypothesis that RNA encoding melatonin receptors undergo a diurnal
      rhythm of expression. To further investigate the possible expression of the
      Mel(1a) receptor subtype in Xenopus retina, we generated Mel(1a) PCR products in
      genomic DNA, and in reverse-transcribed neural retina and retinal pigment
      epithelium (RPE) RNA. The identity of the PCR product was confirmed by
      sequencing. Therefore, all three known Xenopus melatonin receptor subtypes appear
      to be expressed in the neural retina and RPE.

PMID- 11457498
TI  - DNA fragmentation in ischemic core and penumbra in focal cerebral ischemia in
      rats.
AB  - Although apoptotic cell death has been suggested to be involved in ischemic
      injury of the brain, the precise mechanisms of ischemic neuronal cell death are
      unknown. Here, we examined the biochemical feature of apoptosis (i.e. DNA
      fragmentation) in male spontaneously hypertensive rats (5-7 months old) subjected
      to photothrombotic distal middle cerebral artery (MCA) occlusion. After MCA
      occlusion, the brain was cut in a cryostat to produce a standard coronal block
      and samples were dissected from the regions corresponding to the ischemic core,
      penumbra and contralateral control areas. Changes in cerebral blood flow (CBF)
      were monitored at 1 mm posterior and 2-4 mm lateral to the bregma by means of a
      laser-Doppler flowmetry. After MCA occlusion, CBF was decreased to 72+/-18 (+/
      S.D.), 50+/-14, and 35+/-11% of the control values at 2, 3, and 4 mm from the
      midline, respectively. DNA fragmentation characteristics of apoptosis were
      examined in these samples by conventional and pulse-field gel electrophoresis. On
      the conventional gel electrophoresis, nucleosomal DNA fragmentation was detected
      in the penumbral zone at 6 h after MCA occlusion. Large DNA fragments of 50 and
      20 kbp were detected in the penumbral zone and also in the ischemic core region
      at 3 h after distal MCA occlusion. The large DNA fragments seen on the pulse
      field gel elecrophoresis were further degraded to small DNA fragments at 6 h
      after MCA occlusion in the penumbral zone but not in the core regions. The
      evolving DNA fragmentation was observed between 3 and 6 h after the onset of
      brain ischemia in the penumbra, suggesting that apoptosis may contribute to the
      development of ischemic infarction.

PMID- 11457499
TI  - Hypothalamic and amygdaloid corticotropin-releasing hormone (CRH) and CRH
      receptor-1 mRNA expression in the stress-hyporesponsive late pregnant and early
      lactating rat.
AB  - This study investigated the expression of corticotropin releasing hormone (CRH)
      and its receptor CRHR-1, and arginine vasopressin (AVP) mRNAs during the stress
      hyporesponsive periods of late pregnancy and lactation (day-3) and in virgin
      stress-responsive females. In situ hybridization histochemistry showed that basal
      CRH mRNA in the paraventricular nucleus (PVN) decreased in pregnant and increased
      in lactating rats (compared with virgin controls), whereas it increased after
      restraint stress only in virgin rats. Basal PVN CRHR-1 mRNA increased markedly in
      all groups but reached lower levels in pregnant rats. Basal AVP mRNA in the
      parvocellular PVN was higher in lactating rats, and in contrast to CRH mRNA, it
      increased after stress in all groups. In medial preoptic area (MPOA) CRH mRNA
      levels were higher in lactating females compared with virgin and pregnant rats,
      and unexpectedly they decreased markedly after stress only in virgin rats. CRH
      mRNA levels in the central and medial nuclei of the amygdala were higher in
      lactating rats than in virgin or pregnant ones, and stress had no effect in
      either group. These data suggest that these stress hyporesponsive periods: (1) do
      not depend on basal CRH mRNA expression in the PVN; (2) appear to have intact
      stress-activated afferent pathways to the PVN, as shown by preservation of CRHR-1
      and AVP responses to stress, but the information may be differently processed;
      (3) are associated with an alteration in a CRH mediated pathway from the MPOA.

PMID- 11457500
TI  - Fas-induced apoptosis of glioma cells is associated with down-regulation of the
      hSCO1 protein, a subunit of complex IV.
AB  - ApoI/Fas belongs to the tumor necrosis factor receptor (TNFR) superfamily and
      mediates cell death in various cell types. Earlier studies from this laboratory
      have shown that Fas-mediated cell death of glioma cells occur, in part, through
      the production of reactive oxygen species (ROS). To further dissect the molecular
      mechanisms that are involved in Fas-induced cell death, we compared gene
      expression between Fas-treated and saline-treated human neuroglioma H4 cells by
      using the technique of mRNA differential display. This approach led to the
      identification of hSCO1, a component of the inner mitochondrial membrane, which
      is required for the correct assembly, and catalytic function of cytochrome-c
      oxidase, as a Fas down-regulated gene. The decrease in hSCO1 mRNA expression was
      time-dependent, becoming most prominent after 4 h of Fas-treatment. Morphological
      changes observed by confocal microscopy revealed that after 4 h of Fas-treatment,
      the cells undergo membrane blebbing and early formation of apoptotic bodies.
      These observations are discussed in terms of their support for an important role
      of mitochondrial events in Fas-induced apoptosis.

PMID- 11457501
TI  - Glycoprotein synthesis at the synapse: fractionation of polypeptides synthesized
      within isolated dendritic fragments by concanavalin A affinity chromatography.
AB  - The synthesis of glycosylated proteins at postsynaptic sites was evaluated by
      combining metabolic labeling of isolated pinched-off dendritic fragments
      (synaptodendrosomes) with glycoprotein isolation by Con A affinity
      chromatography. Three major labeled proteins were detected (apparent molecular
      weights of 128, 42 and 19 kDa) along with seven minor polypeptides. Treatment of
      the glycoprotein fraction with N-glycosidase F led to shift in the apparent
      molecular weight of the bands. Also, label incorporation into glycoprotein
      species was blocked by tunicamycin. Thus, the three prominent polypeptides and
      most of the minor components of this fraction corresponded to bona fide N
      glycoproteins. Incubation of synaptodendrosomes with cycloheximide also inhibited
      label incorporation into the isolated glycoproteins, indicating that the labeling
      resulted from local de novo synthesis. Subcellular fractionation revealed that
      the labeled glycoproteins were present in soluble and particulate fractions,
      mainly microsomes and synaptic membranes, and one of the species (42 kDa)
      appeared in the incubation medium, indicating secretion. In addition, these
      glycoproteins were dissimilarly distributed in several brain regions, and were
      expressed differentially during development, reaching their highest level of
      synthesis during the period of synaptogenesis. These results provide evidence for
      local dendritic synthesis of particular glycoprotein components of the synapse.

PMID- 11457502
TI  - Protein synthesis at the synapse: developmental changes, subcellular localization
      and regional distribution of polypeptides synthesized in isolated dendritic
      fragments.
AB  - This study evaluated local protein synthesis in subcellular fractions of pinched
      off dendrites (synaptodendrosomes) from different brain regions and at different
      developmental ages. Synaptodendrosomes were labeled with [35S]methionine and
      newly synthesized proteins were characterized by SDS-PAGE and phosphorimaging.
      The same set of approximately 30 cycloheximide-sensitive labeled bands was
      observed in synaptodendrosomes isolated from different brain regions, although
      the relative enrichment of some individual bands varied. Labeling of several
      major proteins was developmentally regulated, revealing three different patterns
      of variation. Subcellular fraction studies revealed that at least 10 labeled
      bands were enriched in synaptic junctions.

PMID- 11457503
TI  - Effect of prolonged hypoxia on Na+ channel mRNA subtypes in the developing rat
      cortex.
AB  - Voltage-gated Na+ channels are regulated in response to oxygen deprivation in the
      mammalian cortex. Past investigations have demonstrated that Na+ channel protein
      expression is up-regulated in the immature brain exposed to prolonged hypoxia.
      Since it is unknown as to which Na+ channel subtype(s) is involved in this
      regulation, we used RT-PCR to assess the effect of hypoxia on Na+ channel I, II
      and III alpha-subunit mRNA expression in the developing rat cortex. Na+ channel
      II mRNA tended to increase during early development, whereas Na+ channel I and
      III did not change or slightly decreased with age. Hypoxic exposure for 1-day had
      no effect on Na+ channel expression, while 5-day hypoxia significantly increased
      Na+ channel III density, with a slight increase in Na+ channel I and no
      appreciable change in Na+ channel II. These results suggest that Na+ channel
      subtype expression in the developing cortex is differentially regulated in
      response to prolonged hypoxic exposure.

PMID- 11457504
TI  - Perforant pathway kindling transiently induces the mRNA expression of GABA-B
      receptor subtypes R1A and R2 in the adult rat hippocampus.
AB  - We examined the gene expression responses of GABA-B R1A, R1B and R2 receptor
      subtypes in the hippocampus of perforant pathway-kindled rats at 24 h and 28 days
      after 15 consecutive daily stimulations. We found R1A expression, but not R1B
      expression, to be significantly induced in the dentate gyrus at 24 h. No change
      in the expression of R1A or R1B was observed at 28 days. R2 expression was
      induced throughout the hippocampus at 24 h, but also returned to control levels
      by 28 days. Thus, our results show that kindling induces a transient increase in
      GABA-B receptor mRNA in the hippocampus.

PMID- 11457505
TI  - Mollusk-derived growth factor: cloning and developmental expression in the
      central nervous system and reproductive tract of Aplysia.
AB  - We have isolated and characterized an atrial gland cDNA that corrects the
      previously reported sequence for Aplysia atrial gland granule-specific antigen
      (AGSA), a glycoprotein of unknown function. We designated the protein mollusk
      derived growth factor (MDGF) to distinguish the revised sequence from AGSA and to
      emphasize its similarity to an insect-derived growth factor (IDGF). We describe
      MDGF mRNA expression that suggests a possible role during embryonic development
      and CNS injury repair.

PMID- 11457506
TI  - Radiation hybrid mapping of 11 alpha and beta nicotinic acetylcholine receptor
      genes in Rattus norvegicus.
AB  - Acetylcholine is the main neurotransmitter of the vestibular efferents and a wide
      variety of muscarinic and nicotinic acetylcholine receptors are expressed in the
      vestibular periphery. To date, 11 nicotinic subunits (alpha and beta) have been
      reported in mammals. Previously, our group [Brain Res. 778 (1997) 409] reported
      that these nicotinic acetylcholine receptor alpha and beta subunits were
      differentially expressed in the vestibular periphery of the rat. To begin an
      understanding of the molecular genetics of these vestibular efferents, this study
      examined the chromosomal locations of these nicotinic acetylcholine receptor
      genes in the rat (Rattus norvegicus). Using radiation hybrid mapping and a rat
      radiation hybrid map server (www.rgd.mcw.edu/RHMAP SERVER/), we determined the
      chromosomal position for each of these genes. The alpha2-7, alpha9, alpha10, and
      beta2-4 nicotinic subunits mapped to the following chromosomes: alpha2, chr. 15;
      alpha3, chr. 8; alpha4, chr. 3; alpha5, chr. 8; alpha6, chr. 16; alpha7, chr. 1;
      alpha9, chr. 14; alpha10, chr. 7; beta2, chr. 2; beta3, chr. 16; and beta4, chr.
      8. With the location for each of these nicotinic subunits known, it is now
      possible to develop consomic and/or congenic strains of rats that can be used to
      study the functional genomics of each of these subunits.

PMID- 11457507
TI  - Methamphetamine-induced alteration in striatal p53 and bcl-2 expressions in mice.
AB  - Methamphetamine (METH)-induced alterations in the expression of p53 and bcl-2
      protein were studied in the striatum of wild type, neuronal nitric oxide synthase
      knockout (nNOS -/-) and copper zinc superoxide dismutase overexpressed (SOD-Tg)
      mice. METH treatment up-regulated p53 and down-regulated bcl-2 expression in the
      striatum of wild type mice. No significant alterations were observed in the
      expression of these proteins in the nNOS -/- or SOD-Tg mice. These data suggest
      that METH might cause its neurotoxic effects via the production of free radicals
      and secondary perturbations in the expression of genes known to be involved in
      apoptosis and cell death machinery.

PMID- 11457508
TI  - Downregulation of free ubiquitin: a novel mechanism of p53 stabilization and
      neuronal cell death.
AB  - Neuronal death through activation of the p53 stress response pathway has been
      implicated in the pathogenesis of neurodegenerative disorders. The mechanisms
      regulating p53 accumulation and function in neurons are poorly understood. Recent
      evidence has demonstrated that Mdm2 is a major inhibitor of p53 that binds to and
      targets p53 for ubiquitin-mediated degradation. Here we demonstrate increased
      expression and co-localization of p53 and Mdm2 in the nuclei of degenerating
      neurons following treatment with either the excitotoxin, kainic acid, or the
      topoisomerase I inhibitor, camptothecin. Co-immunoprecipitation studies showed
      that p53-Mdm2 complexes were present in neuronal lysates. Dual immunofluorescence
      microscopy demonstrated that these complexes accumulated in neurons with a
      striking decrease in free ubiquitin levels. Exogenous ubiquitin restored p53
      degradation to extracts from injured neurons confirming that Mdm2 function was
      intact. Finally, antisense-mediated downregulation of ubiquitin in cultured
      hippocampal neurons resulted in p53 and Mdm2 accumulation as well as apoptotic
      death. These results point to a novel mechanism to stabilize p53 and promote
      neuronal cell death in the central nervous system.

PMID- 11457509
TI  - Differential expression of the cationic amino acid transporter 2(B) in the adult
      rat brain.
AB  - L-Arginine is a substrate for the synthesis of proteins, nitric oxide (NO),
      creatine, urea, proline, glutamate, polyamines and agmatine. In the central
      nervous system (CNS), arginine is extracted from the blood and exchanged by cells
      through carriers called cationic amino acid transporters (CAT) and belonging to
      the so-called system y+. In order to better understand the arginine transport in
      the CNS, we studied in detail the regional distribution of the cells expressing
      the CAT2(B) transcript in the adult rat brain by non-radioisotopic in situ
      hybridization. We show that CAT2(B) is expressed in neurons and oligodendrocytes
      throughout the brain, but is not detected in astrocytes. The pattern of
      localization of CAT2(B) in the normal adult rat brain fits closely that of CRT1,
      a specific creatine transporter. Our study demonstrates that the in vivo
      expression of CAT2(B) differs from that reported in vitro, implying that local
      cellular interactions should be taken into account in studies of gene regulation
      of the CAT2(B) gene. Our work suggests that CAT2(B) may play a role in case of
      increased NO production as well as arginine or creatine deficiency in the brain.

PMID- 11457510
TI  - The modification of NMDA receptors by visual experience in the rat retina is age
      dependent.
AB  - Extensive studies have shown that the activation of N-methyl-D-aspartate
      receptors (NMDARs) and the subsequent rise in the levels of postsynaptic calcium
      are critical events in the initiation of synaptic plasticity. Modification of the
      amount, or of the subunit composition of NMDARs, alters receptor function thereby
      affecting the development and/or efficacy of synaptic transmission. In the
      present study, a Western blot analysis was employed to investigate the effects of
      visual experience and age on the differential expression of NMDARs in the rat
      retina. A crude synaptic membrane fraction (SPM) was prepared and assayed with
      antibodies specific for either the NR1, NR2A or NR2B subunits. Relative to
      control animals raised in a diurnal light-dark cycle, a period of 1 week of dark
      rearing caused an increase in the relative amount of NR1, a decrease in the level
      of NR2A, and no change in the level of NR2B subunit expression in postnatal day
      12 rats. At 2 months of age, 1 week of dark-rearing had less effect, and at 6
      months of age there was no difference between dark-reared and control animals.
      The effect of light exposure on dark-reared animals was tested for the 2-month
      old animals. Light exposure for long periods (days), but not short periods (h),
      could reverse the dark-rearing effects. These data provide evidence for a
      developmentally regulated plasticity of NMDAR subunits in the retina.

PMID- 11457511
TI  - An introduction to neuronal cholecystokinin.
AB  - This issue of Peptides was inspired by a gathering of CCK researchers at the
      first Neuronal Cholecsytokinin Gordon Conference. The papers in this issue
      reflect the diversity of CCK research and demonstrate how the field has matured.
      Reviews describe the regulation of CCK gene expression and CCK release, the
      nature of the hormone binding site of the CCK A receptor, interaction of CCK,
      dopamine and GABA, the role of CCK in thermoregulation, sexual behavior and
      satiety in rodents and humans. The research articles document features of
      cardiovascular regulation, reduced cocaine sensitization and decreased satiety in
      rats that lack the CCK A receptor. Pro CCK processing in neuroblastoma cells and
      the elevation of CCK levels in CSF in a model of chronic pain are detailed in
      other articles. Three articles using different behavioral paradigms in rat and
      sheep examine CCK in learning and memory. Two articles that examine CCK in
      different behaviors that have a dopaminergic component are included. Other
      articles describe the interaction between a 5HT(3) antagonist and CCK-induced
      satiety and c-fos activation and document secretion of oxytocin and vasopressin
      in female patients and controls in response to CCK 4 administration. There is
      good reason to believe that the future is bright for research on CCK. With the
      organization of national and international meetings, CCK researchers have a forum
      for communication. Opportunities for cooperation and collaboration have never
      been better. The easy integration of academic basic and clinical science with
      industrial science bodes very well for the advancement of our understanding of
      the multiple roles that CCK plays in the brain and for the future development of
      CCK-based therapies.

PMID- 11457512
TI  - Cholecystokinin gene transcription: promoter elements, transcription factors and
      signaling pathways.
AB  - Cholecystokinin (CCK) is a neuropeptide expressed in the small intestine and in
      the central and peripheral nervous system. CCK gene expression is both spatially
      and temporally regulated. In neurons CCK production is increased by growth
      factors, cyclic adenosine 3', 5'-monophosphate (cAMP), dopamine, estrogen, and
      injury situations, while intestinal CCK expression is mainly regulated by food
      intake. The function of the proximal CCK promoter has been examined by
      transfection of human CCK-CAT reporter constructs in cultured cells, DNase I
      footprinting and gel shift assays. These studies have led to the identification
      of regulatory elements and transcription factors important for basal and
      stimulated gene expression and depicted the signaling pathways involved in growth
      factor and cAMP induced CCK transcription. The review outlines the current
      knowledge of the regulation of CCK transcription and describes the role of
      putative transcription factors in tissue-specific CCK gene expression.

PMID- 11457513
TI  - Regulation of cholecystokinin release from central nerve terminals.
AB  - The high abundance of the cholecystokinin octapeptide in various brain regions is
      expressed by involvement of this neuropeptide in diverse brain functions. This
      peptide is mostly, if not always, co-localized with classic transmitters in
      central nerve terminals. Since the functions of the coexisting transmitters are
      often different, differential regulation of their release is obvious. This
      differentiation is realized by differences in presynaptic localization, release
      dynamics, and calcium regulation. In addition, CCK release is locally modulated
      by receptors, kinases and phosphatases. The regulatory mechanisms of CCK release
      are placed into physiological perspective.

PMID- 11457514
TI  - Characterization of the type A cholecystokinin receptor hormone-binding domain:
      use of contrasting and complementary methodologies.
AB  - Insights into the molecular basis of binding of the peptide hormone,
      cholecystokinin, to its G protein-coupled receptor is of substantial interest and
      may contribute to the successful production and refinement of receptor-active
      drugs. A number of methodological approaches provide complementary data to
      contribute to these insights. These include receptor mutagenesis, ligand
      structure-activity data, conformational analysis of ligand and receptor
      fragments, and photoaffinity labeling. In this work, we compare and contrast each
      of these methods and provide our current view of the cumulative impact of the
      current data on molecular conformational models of the agonist-occupied type A
      cholecystokinin receptor. These support the key roles played by extracellular
      loop and tail regions of this receptor for binding its natural peptide ligand.

PMID- 11457515
TI  - Cholecystokinin/dopamine/GABA interactions in the nucleus accumbens: biochemical
      and functional correlates.
AB  - The present article reviews our recent biochemical and microdialysis studies
      showing the evidence for an antagonistic CCK(B)/D(2) receptor interaction in the
      regulation of dopaminergic transmission in the nucleus accumbens and GABAergic
      transmission in the ipsilateral ventral pallidum. Since the nucleus accumbens
      plays a crucial role in regulating the output from the limbic system and
      consequently motivation, it may be speculated that a dysregulation of this
      receptor interaction may have consequences in a wide range of central nervous
      system disorders.

PMID- 11457516
TI  - Estrogen and endogenous opioids regulate CCK in reproductive circuits.
AB  - This review focuses on the interaction of estrogen with the cholecystokinin (CCK)
      and endogenous opioid peptide systems in the medial preoptic nucleus, and how
      these interactions result in alterations of a stereotypic female reproductive
      behavior--lordosis. The medial preoptic nucleus is an integral part of a circuit
      controlling lordosis that extends from the limbic system through the
      hypothalamus. Estrogen alters the integration of sensory information in the
      circuit that results in the display of sexually receptive behavior. Estrogen
      determines the activity of CCK and endogenous opioid peptide systems through
      regulation of expression, release and interaction with specific receptors.
      Studies of each system individually have indicated that they are pivotal to the
      expression of lordosis. Recent studies demonstrate an estrogen-dependent
      interaction between endogenous opioid and CCK systems that control reproductive
      behavior.

PMID- 11457517
TI  - Cholecystokinin and thermoregulation--a minireview.
AB  - Thermoregulatory effects of cholecystokinin (CCK) peptides are reviewed with
      special emphasis on two types of responses, that is hypothermia or hyperthermia.
      In rodents exposed to cold a dose-dependent hypothermia has been observed on
      peripheral injection of CCK probably acting on CCKA receptors. Central
      microinjection of CCK in rats induced a thermogenic response that could be
      attenuated by CCKB receptor antagonists, but some authors observed a hypothermia.
      It is suggested that neuronal CCK may have a specific role in the development of
      hyperthermia, and endogenous CCK-ergic mechanisms could contribute to the
      mediation of fever. Possible connections between thermoregulatory and other
      autonomic functional changes induced by CCK are discussed.

PMID- 11457518
TI  - Estradiol, CCK and satiation.
AB  - Estradiol has long been known to inhibit feeding in animals, but the mechanism(s)
      mediating its effects have not been clear. Demonstrations that estradiol's
      feeding effects are expressed as decreases in meal size coupled with the emerging
      consensus that cholecystokinin (CCK) released from the small intestines during
      meals is a physiological negative-feedback signal controlling meal size (i.e.
      satiation) suggested a new approach to the problem of the mechanisms of
      estradiol's inhibitory effect on feeding. Progress on this approach is reviewed
      here. Experimental manipulations of exogenous and endogenous CCK and estradiol
      have produced converging evidence that estradiol cyclically increases the
      activity of the CCK satiation-signaling pathway so that meal size and food intake
      decrease during the ovulatory or estrus phase of the ovarian cycle. This is a
      striking example of the modulation of the operation of a control of meal size by
      the physiological context in which the meal occurs. Estradiol also produces a
      tonic decrease in meal size, but this apparently does not involve the CCK
      satiation-signaling pathway. Where and how estradiol acts to increase the potency
      of the CCK satiating-signaling pathway are not known. Several possible sites are
      suggested by the observations that estradiol treatment increases feeding- and CCK
      induced expression of c-Fos in ovariectomized animals in brain areas including
      the nucleus tractus solitarius, paraventricular nucleus of the hypothalamus, and
      central nucleus of the amygdala. Tests with null mutation mice indicate that
      estrogen receptor-alpha is necessary for estradiol's feeding effects. Finally,
      the possibilities that estradiol exerts important influences on normal or
      disordered eating in women are discussed. It is concluded that estradiol exerts a
      biologically significant action on CCK satiation in animals. Further research to
      determine whether this action of estradiol has a role in the pathogenesis,
      course, or treatment of disordered eating in women is indicated.

PMID- 11457519
TI  - The effect of cholecystokinin in controlling appetite and food intake in humans.
AB  - The present review of the satiating effect of cholecystokinin in humans has
      revealed that cholecystokinin is a physiological satiety factor in humans. The
      results demonstrate the efficacy of the satiating actions of exogenous and
      endogenous CCK in humans. The therapeutic potential of CCK analogues cannot be
      estimated until further studies are performed that demonstrate the efficacy of
      CCK analogues for decreasing body weight, and the safety of CCK when administered
      repetitively for prolonged periods.

PMID- 11457520
TI  - Neuronal cell lines expressing PC5, but not PC1 or PC2, process Pro-CCK into
      glycine-extended CCK 12 and 22.
AB  - Endocrine tumor cells in culture and in vitro cleavage assays have shown that PC1
      and PC2 are capable of processing pro-CCK into smaller, intermediate and final,
      bioactive forms. Similar studies have shown that PC5 has the ability to process a
      number of propeptides. Here, we use GT1-7 (mouse hypothalamic) and SK-N-MC and SK
      N-SH (human neuroblastoma) tumor cell lines to study the ability of PC5 to
      process pro-CCK. RT-PCR and Western blot analysis showed that the cells express
      PC5 mRNA and protein, but not PC1 or PC2. They were engineered to stably
      overexpress CCK and cell media was analyzed for pro-CCK expression and cleavage
      of the prohormone. Radioimmunoassays showed that pro-CCK was expressed, but no
      amidated CCK was detected. Lack of production of amidated CCK may be due to the
      lack of the appropriate carboxypeptidase and amidating enzymes. Production of
      glycine-extended CCK processing products was evaluated by treatment of media with
      carboxypeptidase B followed by analysis with a CCK Gly RIA. Glycine-extended
      forms of the peptide were found in the media. The predominant forms co-eluted
      with CCK 12 Gly and CCK 22 Gly on gel filtration chromatography. The results
      demonstrate that these cell lines which express PC5 and not PC1 or PC2 have the
      ability to process pro-CCK into intermediate, glycine-extended forms more closely
      resembling pro-CCK products in intestine than in brain.

PMID- 11457521
TI  - Cholecystokinin-8 (CCK-8) has no effect on heart rate in rats lacking CCK-A
      receptors.
AB  - Heart rate responses to i.v. administration of cholecystokinin-8 (CCK-8) were
      investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-A
      receptors and control Long-Evans Tokushima Otsuka (LETO) rats. The heart rate
      decreased after i.v. administration of 3 nmol.kg(-)(1) of CCK-8 in LETO rats, but
      not in OLETF rats. Bradycardia in the LETO rats disappeared after treatment with
      MK-329, but not after treatment with L-365,260. The expression of CCK-A receptor
      precursor mRNA was found exclusively in the atrium in LETO rats. These results
      suggest that CCK-8 decreases heart rate via CCK-A receptors located in the atrium
      of the rats.

PMID- 11457522
TI  - OLETF (Otsuka Long-Evans Tokushima Fatty) rats that lack the CCK 1 (A) receptor
      develop less behavioral sensitization to repeated cocaine treatment than wild
      type LETO (Long Evans Tokushima Otsuka) rats.
AB  - OLETF (Otsuka Long-Evans Tokushima Fatty) lacking the CCK 1 (A) receptor have
      similar spontaneous activity and locomotor response (horizontal and vertical
      activity) in response to a single injection of cocaine as the wild type LETO
      (Long Evans Tokushima Otsuka) rats. In contrast, the OLETF rats display more
      stereotypy in response to the first dose of cocaine than the LETO rats. Tested at
      7 and 14 days after a one week daily treatment with cocaine, the LETO rats
      display robust behavioral sensitization to cocaine while the OLETF rats did not.
      These results support the hypothesis that endogenous CCK released by cocaine
      treatment and acting at CCK 1 receptors is required for the development and/or
      expression of this behavior.

PMID- 11457523
TI  - Cholecystokinin modulation of apomorphine- or amphetamine-induced stereotypy in
      rats: opposite effects.
AB  - Stereotyped behavior can be induced by the dopamine agonist apomorphine or by the
      releasing agent amphetamine. Cholecystokinin influence on dopamine-mediated
      behaviors has been extensively studied but a real controversy remains. Our
      purpose was to further characterize the dopamine-cholecystokinin interaction in
      apomorphine- and amphetamine-induced stereotyped behavior using sulphated
      cholecystokinin octapeptide (CCK8) and cholecystokinin tetrapeptide (CCK4)
      treatments. The results showed that CCK8 decreases apomorphine-induced
      stereotyped behavior and CCK4 has no effect. CCK4 and CCK8 increased the
      amphetamine-induced stereotyped behavior; CCK4 was more effective. The results
      confirm the opposite modulation of apomorphine or amphetamine-induced stereotyped
      behavior by CCK. These data suggest that this modulation is mediated by both CCK
      receptors on apomorphine-induced and only by CCK(2) receptors on amphetamine
      induced stereotyped behavior.

PMID- 11457524
TI  - Stimulation of either cholecystokinin receptor subtype reduces while antagonists
      potentiate or sensitize a morphine-induced excitatory response.
AB  - Cholecystokinin peptides (CCK) have been shown to antagonize many opioid-mediated
      effects. The present study was undertaken to determine whether peripheral
      injections of cholecystokinin sulphated octapeptide (CCK8), cholecystokinin
      tetrapeptide (CCK4), the CCK(1) (lorglumide) and the CCK(2) (PD-135,158 and LY
      225910) receptor antagonists can influence a classic morphine excitatory effect,
      i.e. the display of Straub tail reaction in mice (STR). A total of 570 female
      Balb/C mice were tested. Experiment 1 was undertaken to determine whether i.p.
      injections of CCK8 or CCK4 can influence STR. Each animal was treated with i.p.
      injections of saline or CCK8 (10 and 20 nmol/kg) or CCK4 (20 and 40 nmol/kg).
      After 30 min all animals received an i.p. injection of morphine hydrochloride
      (10.0 mg/kg). The highest doses of both CCK8 (35% STR) and CCK4 (40% STR)
      significantly reduced STR as compared to saline (85% STR) treated mice (Fisher
      test; P < 0.01). In experiment 2 each animal was treated with ip injections of
      saline or 1.0 mg/kg lorglumide or PD-135,158 fifteen minutes before an injection
      of morphine at doses ranging from 1.0 to 50.0 mg/kg. In experiment 3 animals were
      treated with injections of saline, 0.1 or 10.0 mg/kg lorglumide or LY-225910
      before an injection of a fixed MC dose (2.0 mg/kg). Both lorglumide and PD
      135,158 induced a significant shift to the left in the morphine dose-response
      curves as well as a significant decrease in ED50 of the STR. ED50 for lorglumide
      was significantly lower than ED50 for PD-135,158. Both doses of lorglumide and
      the highest dose of LY-225910 significantly increased the percent of animals
      displaying STR. Experiment 4 was undertaken to determine whether repeated
      peripheral injections of morphine or the morphine-potentiating agents CCK(1)
      (lorglumide) and the CCK(2) (LY-225910) receptor antagonists can induce morphine
      sensitization. Each animal was treated with 5 daily i.p. injections of saline
      (control group), 1.5 mg/Kg morphine hydrochloride (group morphine), and 1.0 mg/Kg
      lorglumide (group LOR) or LY-225910 (group LY). One, two, three and four weeks
      after the last treatment day, all animals were challenged with one i.p. injection
      of morphine (1.5 mg/Kg). The morphine, LOR groups and group LY showed a
      significant increase in percentage of animals displaying STR. These data
      demonstrate that the blockade of endogenous CCK actions leads to morphine
      sensitization probably through both CCK receptors. The present data are
      consistent with the antagonistic effects of CCK and opioids in the control of
      morphine-induced STR. In addition, these results suggest that both CCK receptors
      are involved in the modulatory effects of CCK on this morphine effect.

PMID- 11457525
TI  - Increased level of cholecystokinin in cerebrospinal fluid is associated with
      chronic pain-like behavior in spinally injured rats.
AB  - Cholecystokinin (CCK) is a physiological antagonist of opioid-mediated
      antinociception and may be involved in some chronic pain states where opioids
      have reduced effect. We have previously shown in a rat model of central
      neuropathic pain after spinal cord injury that blockade of CCK-B receptors lead
      to marked pain relief. In the present study, we showed that spinally injured rats
      exhibiting chronic pain-like behaviors (aversive reaction to innocuous mechanical
      and cold stimulation) had significantly elevated level of CCK-like
      immunoreactivity in cerebrospinal fluid compared to normal rats or spinally
      injured rats which did not exhibit pain-like behaviors. The increased level of
      circulating CCK in the cerebrospinal fluid may thus contribute to the maintenance
      of chronic pain in these rats by reducing the endogenous inhibitory tone provided
      by opioid peptides and may be involved in the phenomenon of opioid insensitivity.

PMID- 11457526
TI  - CCK and development of mother preference in sheep: a neonatal time course study.
AB  - We investigated the effects of a CCK-A receptor antagonist on the development of
      mother preference. Lambs received 2-NAP either at birth or 6, or 12 h later.
      Controls were given saline. When tested at 24 h of age, lambs receiving 2-NAP at
      birth or 6 h later did not display mother preference unlike controls and lambs
      which were given 2-NAP at 12 h. The effect of the antagonist persisted at 48 h of
      age in lambs treated at birth. This suggests that endogenous CCK participates in
      the development of mother preference only in the first few hours following birth.

PMID- 11457527
TI  - Examining the role of cholecystokinin in appetitive learning in the infant rat.
AB  - The role of Cholecystokinin (CCK), a gut hormone and neuropeptide, in early
      learning was examined. Pairing a novel odor (presented away from the nest) with
      exogenously administered CCK (0.25 & 0.5 microg/kg IP) has been shown to produce
      a conditioned-odor preference in infant rats (Weller, A.; Blass, E.M. Behav.
      Neurosci. 104:199-206; 1990). This suggests that CCK can act as a positive
      unconditioned stimulus (UCS). In the present study the possibility that CCK
      mediates learning was examined in 12-day-old rats, using rewards that represent
      aspects of the dam and the nest. In Experiments 1 and 2, pups received the
      selective CCK1 receptor antagonist devazepide (600 microg/kg), the selective CCK2
      receptor antagonist L365,260 (600 microg/kg), or vehicle. In a series of training
      trials, choosing a particular floor texture was rewarded by 20 sec. on a rug
      texture (experiment 1) or with maternal (feces) odor (experiment 2). In
      experiment 3, after administering devazepide (0, 600, or 1000 microg/kg) a novel
      odor was paired once with reunion of the pup with its dam. The dependent measure
      in all studies was the pup's relative preference toward the (tactile or
      olfactory) conditioned stimulus (CS), determined in preference tests. Conditioned
      preferences were evident in all experiments. The CCK receptor antagonists did not
      increase conditioned preference levels. L365, 260 (experiment 2) and devazepide
      (experiment 1) clearly blocked the appearance of the conditioned effect in one of
      the experiments. In addition, devazepide treatment eliminated the conditioned
      effect in the two other experiments, by increasing preference levels in the
      control groups. In summary, the results suggest that endogenous CCK mediates some
      aspects of the infant's acquisition of new associations. The role of the two
      receptor-subtypes appears to be different, depending on the context and the
      nature of the rewarding stimulus.

PMID- 11457528
TI  - Repeated treatment with cholecystokinin octapeptide improves maze performance in
      aged Fischer 344 rats.
AB  - Previous studies have shown that sulfated cholecystokinin octapeptide (CCK-8S)
      can improve learning in adult rodents when administered systemically or into the
      central nucleus of amygdala. Here we analyzed the effect of repeated
      intraperitoneal (i.p.) injection of CCK-8S on the performance of 26-month-old
      Fischer 344 rats in different versions of the Morris water maze and in a rota-rod
      test of motor coordination. Old rats were injected daily with different doses of
      CCK-8S (0.32 to 8.0 microg/kg; IP) 10 min before the behavioral tests. Control
      groups included vehicle-injected old and adult (3-month-old) F 344 rats. To
      control for a possible development of tolerance to the behavioral effects of
      repeated CCK-8S administration, groups of aged rats were included which were
      subjected to an acute rather than a repeated CCK injection schedule. The repeated
      administration of CCK-8S did not influence the performance of the old rats in the
      hidden-platform version of the maze. In addition, the acute treatment with CCK-8S
      failed to modify navigation performance in this task, suggesting that drug
      tolerance may not account for the lack of behavioral effects seen after repeated
      CCK-8S injection. During the "probe trial", the percentage of animals per group,
      which swam exactly across the former platform site, was markedly increased in
      aged rats treated repeatedly with 1.6 microg/kg CCK-8S. This might be indicative
      of improved retention of the prior platform location and/or a higher resistance
      of the learned escape response to extinction. The specificity of the effect of
      CCK-8S on processes related to spatial learning and memory is supported by the
      lack of effect on motor performance.

PMID- 11457529
TI  - Ondansetron attenuates CCK induced satiety and c-fos labeling in the dorsal
      medulla.
AB  - Serotonin 5-HT(3) antagonists have been suggested for treatment of several
      disorders involving altered gastrointestinal (GI) function. CCK also has well
      documented GI actions on both food intake and vago-vagal reflexes. To evaluate
      potential interactions, the effect of a 5-HT(3) antagonist, ondansetron, on
      exogenous CCK induced satiety and c-fos activation was determined. Ondansetron
      reduced both actions of CCK by approximately 50%. The reduction in c-fos was
      localized to a specific subregion of the dorsal medulla, suggesting that a
      distinct subpopulation of CCK receptive fibers are modulated by 5-HT(3) ligands.
      Treatments using 5-HT(3) antagonists also may affect endogenous CCK functions.

PMID- 11457530
TI  - Attenuated satiation response to intestinal nutrients in rats that do not express
      CCK-A receptors.
AB  - Pharmacological experiments suggest that satiation associated with intestinal
      infusion of several nutrients is mediated by CCK-A receptors. Otsuka Long-Evans
      Tokushima Fatty, (OLETF), rats do not express CCK-A receptors and are insensitive
      to the satiation-producing effects of exogenous CCK. To further evaluate the role
      of CCK-A receptors in satiation by intestinal nutrient infusion, we examined
      intake of solid (pelleted rat chow) or liquid (12.5% glucose) food intake,
      following intestinal infusions of fats (oleic acid or fat emulsion), sugars
      (maltotriose or glucose), or peptone in OLETF rats and Long Evans Tokushima
      Otsuka control rats (LETO). Intestinal infusion of glucose or maltotriose reduced
      solid food intake more in LETO than in OLETF rats from 30 min through 4 h post
      infusion. Reduction of solid food intake by intestinal infusions of fat or
      peptone did not differ between OLETF and LETO rats during the first 30 min post
      infusion, but reduction of intake by these infusates was attenuated in OLETF rats
      over the ensuing 4h post infusion. Intestinal infusion of glucose, oleate, fat
      emulsion and peptone reduced 30-min intake of 12.5% glucose more in LETO than
      OLETF rats. Furthermore, pretreatment with the CCK-A receptor antagonist,
      devazepide, attenuated intestinal nutrient-induced reduction of food intake only
      in LETO, but not OLETF rats. Our results confirm pharmacological results,
      indicating that CCK-A receptors participate in satiation by nutrients that
      elevate plasma CCK concentrations, as well as by nutrients that do not stimulate
      secretion of endocrine CCK. In addition, our results indicate: 1) that OLETF rats
      have deficits in the satiation response to a variety of intestinal nutrient
      infusions; 2) that the temporal pattern for CCK-A receptor participation in
      satiation by intestinal nutrients is different during ingestion of liquid and
      solid foods and 3) that intestinal nutrients provide some satiation signals that
      are CCK-A receptor mediated and some that are not.

PMID- 11457531
TI  - Arginine-vasopressin and oxytocin response to cholecystokinin-tetrapeptide.
AB  - This study examined the effects of i.v. administration of cholecystokinin
      tetrapeptide (CCK-4) on plasma release of arginine vasopressin (AVP) and oxytocin
      (OT) in women with premenstrual dysphoric disorder (PMDD) and control women,
      during both the follicular phase and the luteal phase of their menstrual cycle.
      Plasma AVP and OT concentrations increased following CCK-4 administration. AVP
      and OT response to CCK-4 was similar for PMDD and control women and unaffected by
      menstrual cycle phase. AVP and OT may play a role in the hypothalamo-pituitary
      adrenal (HPA) axis activity associated with the panic response induced by CCK-4.

PMID- 11457532
TI  - Recombinant BCG vaccines.

PMID- 11457533
TI  - A Brucella ovis antigenic complex bearing poly-epsilon-caprolactone
      microparticles confer protection against experimental brucellosis in mice.
AB  - A hot saline antigenic extract (HS) from Brucella ovis was encapsulated in poly
      epsilon-caprolactone microparticles (PEC), and tested as a vaccine against B.
      ovis and B. abortus infections in mice. Subcutaneous but not oral administration
      in BALB/c mice of the HS-PEC induced high amounts of IFN-gamma and IL-2 but low
      quantities of IL-4 suggesting a combined Th1/Th2 cellular immune response. The
      vaccine administered either subcutaneously or orally protected mice against B.
      ovis infection. Such protection was similar to that provided by the reference
      living attenuated B. melitensis Rev. 1 vaccine. By contrast, only the
      subcutaneous vaccination with HS-PEC was as effective as Rev. 1 in conferring
      protection against B. abortus infection. The use of free HS or empty PEC
      microparticles did not produce any protective effect.

PMID- 11457534
TI  - Efficient induction of antigen-specific, T helper type 1-mediated immune
      responses by intramuscular injection with ovalbumin/interleukin-18 fusion DNA.
AB  - The balance of two types of T helper (Th) cells, Th1 and Th2 subsets, is
      important with respect to susceptibility or resistance to particular infections,
      or to autoimmune diseases and allergic diseases. To effectively induce Th1 immune
      responses in an antigen-specific manner, we constructed a mammalian expression
      plasmid (pOVA/IL-18) carrying a fusion gene in which the ovalbumin (OVA; a model
      antigen) cDNA was covalently linked to mature interleukin-18 (IL-18) cDNA.
      Intramuscular injection of C57BL/6 mice with the pOVA/IL-18 DNA efficiently
      increased the production of both OVA-specific IFN-gamma and anti-OVA IgG2a
      isotype, compared with the injection with the pOVA DNA. In addition, the pOVA/IL
      18 was more efficient than a simple mixture of pOVA and pIL-18 in inducing
      antigen-specific, Th1 immune responses and in inhibiting OVA-specific, IL-4
      production. These studies indicate that vaccination with the OVA/IL-18 fusion DNA
      efficiently induces Th1 immune response in an antigen-specific manner.

PMID- 11457535
TI  - The human IgG3 hinge mediates the formation of antigen dimers that enhance
      humoral immune responses to DNA immunisation.
AB  - A series of plasmid DNA constructs containing the 45W antigen gene from Taenia
      ovis were used to investigate the impact of antigen dimerisation on the humoral
      immune response to genetic immunisation. Genes encoding dimeric 45W were
      generated via fusion to the hinge region of human IgG3 (hIg). This region was
      selected because it is compact and contains 11 inter-chain disulphide-bridges.
      The DNA encoding the IgG3 hinge contains four exons, with the last three exons
      being repeats and possibly superfluous. Plasmids containing the 45W gene linked
      to exons 1-2, 1-3 or 1-4 of the hIgG3 hinge, were compared to a control plasmid
      containing a form of the 45W gene which encodes secreted, monomeric 45W protein.
      Western blot analysis was used to investigate the formation of the fusion
      proteins in transfected Cos-7 cells. The full-length fusion construct expressed
      predominantly dimeric forms of the fusion-protein, while truncation of the hinge
      region decreased the abundance of dimeric fusion-protein and increased the
      proportion monomeric fusion antigen. In immunised BALB/c mice, 45W-specific
      antibody titres were increased 3 to 4-fold via fusion to the full-length hinge
      region, whereas the truncated constructs were similar to the control. IgG
      subclass analysis indicated that all mice generated predominantly IgG1, IgG2a and
      IgG2b antibodies. Therefore, these results suggest that the efficient formation
      of dimeric antigen, via fusion to the full-length hinge of human IgG3, can
      increase the immunogenicity of expressed antigens without altering the form of
      the immune response elicited by DNA immunisation.

PMID- 11457536
TI  - Induction of a cytotoxic T-cell response to HIV-1 proteins with short synthetic
      peptides and human compatible adjuvants.
AB  - The goal of this study was the induction of a strong CTL response against
      multiple CTL epitopes present in HIV proteins using short synthetic peptides.
      Four HLA-A2.1 restricted peptides (RT 476-484, p17 77-85, gp41 814-823, RT 956
      964) that showed stable binding to the HLA-A2.1 molecule in an in vitro binding
      assay were able to elicit a strong specific immune response in HLA-A2.1
      transgenic mice when injected with IFA or Montanide. The use of biodegradable
      microspheres (MS) as adjuvant was also successfully tested for all peptides. When
      the peptides were injected as a mixture the response was weaker as compared to
      individual injections of the peptides indicating the occurrence of
      immunodominance (ID). We are currently investigating whether ID can be overcome
      by a combined injection of peptide loaded MS with different release patterns.
      Taken together, it seems feasible to induce a specific CTL response in HLA-A2.1
      transgenic mice against several HIV proteins using short synthetic peptides and
      human compatible adjuvants.

PMID- 11457537
TI  - Cost analysis of two strategies for hepatitis A vaccination of hospital health
      care personnel in an intermediate endemicity area.
AB  - The aim of the study was to carry out a cost analysis to allow the comparison of
      the cost of two vaccination strategies against Hepatitis A in health-care
      personnel. A total of 423 health-care workers were recruited at one General
      Hospital of Madrid, Spain. Blood specimens were obtained for anti-HAV antibody
      determination. The prevalence of anti-HAV antibody was 40% (95% CI: 35-45) and it
      was directly correlated with age. Cost analysis determined that the critical
      value of prevalence for vaccination with HAV vaccine was 23%. In hospital health
      care workers < or =30 years in age, vaccination with HAV vaccine (without
      screening) would be the less costly strategy. In those >30 years in age, it would
      be less costly to screen for anti-HAV antibody first and vaccinate those who are
      antibody-negative.

PMID- 11457538
TI  - Identification of vaccine candidate antigens from a genomic analysis of
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a key periodontal pathogen which has been implicated
      in the etiology of chronic adult periodontitis. Our aim was to develop a protein
      based vaccine for the prevention and or treatment of this disease. We used a
      whole genome sequencing approach to identify potential vaccine candidates. From a
      genomic sequence, we selected 120 genes using a series of bioinformatics methods.
      The selected genes were cloned for expression in Escherichia coli and screened
      with P. gingivalis antisera before purification and testing in an animal model.
      Two of these recombinant proteins (PG32 and PG33) demonstrated significant
      protection in the animal model, while a number were reactive with various
      antisera. This process allows the rapid identification of vaccine candidates from
      genomic data.

PMID- 11457539
TI  - A novel bipolar mode of attachment to aluminium-containing adjuvants by BBG2Na, a
      recombinant subunit hRSV vaccine.
AB  - Human respiratory syncytial virus (hRSV) is a major pathogen responsible for
      bronchiolitis and severe pulmonary disease in very young children,
      immunodeficient patients and the elderly. BBG2Na, a recombinant chimeric protein
      produced in Escherichia coli, is a promising subunit vaccine candidate against
      this respiratory pathogen, composed of G2Na, the central domain of RSV G
      glycoprotein, and BB, an albumin binding domain of streptococcal protein G.
      BBG2Na has a basic isoelectric point (pI 9.3) and as expected, is strongly
      adsorbed by aluminium phosphate (AP). Surprisingly, BBG2Na is also strongly
      adsorbed by aluminium hydroxide (AH), which normally binds molecules with acidic
      isoelectric points. This behaviour was unexpected according to the well
      established adsorption model of Hem and co-workers. Our observations may be
      explained by the bipolar two-domain structure of the BBG2Na chimera which is not
      reflected by the global basic isoelectric point of the whole protein: the BB
      domain has an acidic isoelectric point (pI 5.5) and the G2Na domain a highly
      basic one (pI 10.0). Importantly, formulation in either aluminium salt resulted
      in equally high immunogenicity and protective efficacy against RSV in mice. From
      a physicochemical point of view, this unique property of BBG2Na makes it
      eminently suitable for combination to either paediatric or elderly multivalent AH
      or AP-containing vaccines already in the market or in development.

PMID- 11457540
TI  - Potentiation by a novel alkaloid glycoside adjuvant of a protective cytotoxic T
      cell immune response specific for a preerythrocytic malaria vaccine candidate
      antigen.
AB  - We have recently demonstrated that the novel glycoalkaloid tomatine, derived from
      leaves of the wild tomato Lycopersicon pimpinellifolium, can act as a powerful
      adjuvant for the elicitation of antigen-specific CD8+ T cell responses. Here, we
      have extended our previous investigation with the model antigen ovalbumin to an
      established malaria infection system in mice and evaluated the cellular immune
      response to a major preerythrocytic stage malaria vaccine candidate antigen when
      administered with tomatine. The defined MHC H-2kd class I-binding 9-mer peptide
      (amino acids 252-260) from Plasmodium berghei circumsporozoite (CS) protein was
      prepared with tomatine to form a molecular aggregate formulation and this used to
      immunise BALB/c (H-2kd) mice. Antigen-specific IFN-gamma secretion and cytotoxic
      T lymphocyte activity in vitro were both significantly enhanced compared to
      responses detected from similarly stimulated splenocytes from naive and tomatine
      saline-immunised control mice. Moreover, when challenged with P. berghei
      sporozoites, mice immunised with the CS 9-mer-tomatine preparation had a
      significantly delayed onset of erythrocytic infection compared to controls. The
      data presented validate the use of tomatine to potentiate a cellular immune
      response to antigenic stimulus by testing in an important biologically relevant
      system. Specifically, the processing of the P. berghei CS 9-mer as an exogenous
      antigen and its presentation via MHC class I molecules to CD8+ T cells led to an
      immune response that is an in vitro correlate of protection against
      preerythrocytic malaria. This was confirmed by the protective capacity of the 9
      mer-tomatine combination upon in vivo immunisation. These findings merit further
      work to optimise the use of tomatine as an adjuvant in malaria vaccine
      development.

PMID- 11457541
TI  - Decline in immunity to polio among young adults.
AB  - A serologic survey was conducted on a population-based representative sample of
      521 18-year-old soldiers recruited to the Israel Defence Forces in 1997. The
      prevalence of neutralizing antibodies and geometric mean titers (GMTs) against
      the three types of poliovirus (Mahoney, MEF and Saukett strains) were found to be
      98.7% (GMT--169.95), 99.6% (GMT--297.14) and 96.4% (GMT - 59.48), respectively.
      These GMTs are markedly lower than those recorded 4 years after booster
      vaccination carried out during a 1988 polio outbreak, and suggest a decline in
      immunity against polio among young adults. These findings support the policy of
      routine revaccination of children and adolescents in countries at risk of
      imported polioviruses and of revaccination of adults traveling to areas to which
      polio is endemic.

PMID- 11457542
TI  - Nasal immunisation with Salmonella typhimurium producing rotavirus VP2 and VP6
      antigens stimulates specific antibody response in serum and milk but fails to
      protect offspring.
AB  - Rotavirus specifically infects the small intestine of young infants resulting in
      severe diarrhoea. Mucosal antibody responses are required to cure the infection,
      and mucosal administration of rotavirus-like particles induces protective
      immunity without requiring a mucosal adjuvant such as cholera toxin. In addition,
      the rotavirus protein VP6 has been defined as a protective antigen in an adult
      mouse rotavirus infection model. Salmonella typhimurium is an epithelium-invasive
      bacterium that induces specific immune responses in mucosal tissues against
      itself and carried antigens. In this work, we investigated the capacity of a live
      recombinant S. typhimurium vaccine to stimulate antibody responses against
      rotavirus. We constructed an attenuated S. typhimurium strain simultaneously
      producing VP6 and VP2 rotavirus proteins in the cytoplasm. In contrast to
      expression in eukaryotic cells, VP6 and VP2 did not form virus-like particles in
      our bacterial system. After nasal administration of female mice, the live
      recombinant Salmonella were able to elicit an antibody response specific to both
      VP2 and VP6 in serum and milk. However, these antibodies failed to passively
      protect the offspring against rotavirus-induced diarrhoea.

PMID- 11457543
TI  - Vaccination against bubonic and pneumonic plague.
AB  - Yersinia pestis is the etiological agent of bubonic and pneumonic plague,
      diseases which have caused over 200 milllion human deaths in the past. Plague
      still occurs throughout the world today, though for reasons that are not fully
      understood pandemics of disease do not develop from these outbreaks. Antibiotic
      treatment of bubonic plague is usually effective, but pneumonic plague is
      difficult to treat and even with antibiotic therapy death often results. A killed
      whole cell plague vaccine has been used in the past, but recent studies in
      animals have shown that this vaccine offers poor protection against pneumonic
      disease. A live attenuated vaccine is also available. Whilst this vaccine is
      effective, it retains some virulence and in most countries it is not considered
      to be suitable for use in humans. We review here work to develop improved sub
      unit and live attenuated vaccines against plague. A sub-unit vaccine based on the
      F1- and V-antigens is highly effective against both bubonic and pneumonic plague,
      when tested in animal models of disease. This vaccine has been used to explore
      the utility of different intranasal and oral delivery systems, based on the
      microencapsulation or Salmonella delivery of sub-units.

PMID- 11457544
TI  - Encapsulation in biodegradable microparticles enhances serum antibody response to
      parenterally-delivered beta-amyloid in mice.
AB  - Poly(lactide-co-glycolide) (PLG) microspheres were tested as a parenteral
      delivery system for human beta-amyloid (1-42) (Abeta), a potential
      immunotherapeutic undergoing assessment in Phase 1 studies for Alzheimer's
      disease (AD). Abeta was successfully encapsulated in PLG microspheres of average
      sizes of 3 or 15 microm diameter. Swiss Webster (SW) mice were injected by the
      sub-cutaneous (s.c.) or intra-peritoneal (i.p.) routes with 3-33 microg Abeta.
      Abeta-PLG microparticles (3 microm) induced dose-dependent antibody responses,
      which were maximal at 33 microg Abeta, while Abeta in phosphate-buffered saline
      (PBS) produced weak antibody responses at the same doses by both routes.
      Significantly increased antibody responses were seen for both small and large
      particle formulations given by the i.p. route in comparison to the s.c route. It
      was previously reported that passive immunisation with Abeta-specific antibodies
      cleared amyloid plaques in a mouse model of AD (Bard F, Cannon C, Barbour R, et
      al. Peripherally administered antibodies against amyloid beta-peptide enter the
      nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature
      Med 2000;6:916-19), an indication that induction of serum antibody is a
      prerequisite for efficacy.

PMID- 11457545
TI  - Modulation of the serological response to meningococcal polysaccharides by
      cytokines.
AB  - Meningococcal A and C but not B capsular polysaccharides stimulated a low level
      primary antibody response, predominantly IgM, and no secondary response in 21-day
      old CBA/A mice. However, in 56-day-old mice a higher proportion of IgG antibody
      and a secondary response were produced. When the polysaccharides were injected in
      conjunction with rDNA derived human interleukin 2 (IL-2) the IgG antibody
      responses were increased in both age groups and memory cells were primed in the
      younger mice. IL-2 increased significantly the IgG antibody response to
      conjugates of A and C polysaccharides with diphtheria mutant protein but exerted
      a minimal effect on the IgG response to B polysaccharide complexed with aluminium
      hydroxide and outer membrane proteins. The stimulatory effect of IL-2 on the
      antibody responses to the polysaccharide antigens was not mediated by T-cells as
      similar results were obtained in athymic (nu/nu) and thymocompetent (nu/+) mice.
      However, the response to the A and C oligosaccharide conjugates was T-cell
      dependent and occurred only in the heterozygotes. In this case the adjuvant
      effect of IL-2 was seen only in the response to the C polysaccharide conjugate
      and was transferable with T-lymphocytes from primed animals.

PMID- 11457546
TI  - Cost-effectiveness of influenza vaccination in high-risk children in Argentina.
AB  - OBJECTIVES: our study aimed to evaluate the cost-effectiveness of influenza
      vaccination in high-risk children in Argentina. METHODS: a decision analysis
      model was performed, using data from published and unpublished sources, to
      compare two strategies--to vaccinate or not to vaccinate. We simulated the
      expected consequences of vaccination on direct medical costs, related to disease
      management and indirect costs, related to lost parental working days
      (absenteeism). RESULTS: Using base-case assumptions vaccination of high-risk
      children aged 6 months to 15 years old, in Argentina (estimated cohort of
      1184748) would prevent 207331 cases of influenza, resulting in a reduction of
      58052 days of hospitalization and 207331 outpatient visits. Vaccination would
      lead to net savings of US$ 11894870 per vaccinated cohort (US$ 10.04 per
      vaccinated child). CONCLUSION: our economic analysis shows that in Argentina,
      routine vaccination of high-risk children against influenza would be cost saving
      for society.

PMID- 11457547
TI  - Detection of anthrax vaccine virulence factors by polymerase chain reaction.
AB  - In Italy, an attenuated Bacillus anthracis strain, named 'Carbosap', is used for
      immunization against ovine and bovine anthrax. Analysis on 'Carbosap', Sterne
      vaccine strain F34 and Pasteur vaccine strain SS104, were performed using primers
      specific for the sequences, encoding the toxic factors, located on plasmids pXO1
      and pXO2 and primers specific for the chromosome. The results obtained from
      polymerase chain reaction (PCR) assay revealed the presence of both plasmids pXO1
      and pXO2 in 'Carbosap' strain. This study showed that the 'Carbosap' vaccine
      strain has a different plasmid pattern in comparison to Pasteur vaccine strain
      SS104 and Sterne vaccine strain F34.

PMID- 11457548
TI  - Therapeutic efficacy of hepatitis B surface antigen-antibodies-recombinant DNA
      composite in HBsAg transgenic mice.
AB  - Therapeutic efficacy of HBsAg-anti-HBs-recombinant DNA harboring hepatitis B
      virus (HBV) S gene complex was compared with three other therapeutic vaccine
      candidates (recombinant HBsAg, HBsAg complexed to anti-HBs antibodies and naked
      plasmid DNA encoding the HBV S gene). After four injections at 3-week intervals,
      the most pronounced decrease of serum HBsAg, the highest titer of anti-HBs
      response, the highest level of interferon-gamma produced by splenocytes and
      potent cytotoxicity T cell response were observed in the HBsAg-anti HBs-sDNA
      immunized group. Reduced expression of HBsAg in hepatocytes was also shown. The
      therapeutic mechanism of HBsAg-anti-HBs-DNA was speculated as modulation of HBsAg
      presentation via both endogenous and exogenous pathways.

PMID- 11457549
TI  - Cytokine adjuvancy of BVDV DNA vaccine enhances both humoral and cellular immune
      responses in mice.
AB  - The effect of cytokine adjuvancy on a bovine viral diarrhoea virus (BVDV) DNA
      vaccine expressing the major glycoprotein E2 was investigated in mice. Murine
      interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) were chosen for their potential ability to enhance the humoral and cellular
      immune responses involved in protection against BVDV. Both cytokines, co
      administered as separate plasmid constructs, had a marked effect on ELISA and
      neutralising antibody titres, improving the spectrum of neutralisation induced by
      the E2 DNA vaccine, as demonstrated in heterologous neutralisation assays. The
      predominance of IgG2a isotypes, in sera from all DNA injected groups, indicated a
      Th1 biased immune response. Antigen specific proliferation of murine splenocytes
      from immunised mice was enhanced by cytokine co-administration, with the highest
      stimulation indexes observed in the group co-injected with the GM-CSF construct.
      These results obtained in the mouse (Balb/c; H2-kd) animal model demonstrate the
      value of the two cytokines as adjuvants for the E2 DNA vaccine. The need for an
      adjuvant in this system was emphasised by the MHC restriction observed when
      C57BL/6 mice (H2-kb) were immunised with the E2 DNA construct. Antibody levels
      were dramatically lower in this mouse strain.

PMID- 11457550
TI  - Lipophilic quaternary ammonium salt acts as a mucosal adjuvant when co
      administered by the nasal route with vaccine antigens.
AB  - Nasal administration of vaccines is an attractive approach which offers several
      significant advantages over traditional intramuscular vaccine delivery. These
      advantages include easier administration and induction of immune responses in the
      mucosal secretions of the body. In this study we describe a new potent nasal
      adjuvant, dimethyldioctadecylammonium bromide (DDA), that induces both mucosal
      and systemic immune responses when co-administered with diphtheria toxoid (DT),
      tetanus toxoid (TT) and BBG2Na antigens. In particular, we show that the nasal
      delivery of recombinant fragment (BBG2Na) of the G protein of respiratory
      syncytial virus (RSV) mixed with DDA induces both local and systemic anti-RSV
      immune responses and protects against viral challenge. Furthermore, we provide
      evidence that the DDA+BBG2Na vaccine does not induce lung immunopathology upon
      subsequent RSV challenge.

PMID- 11457551
TI  - Response to HBV vaccine in relation to vaccine dose and anti-HCV positivity: a
      New South Wales correctional facilities' study.
AB  - Currently, about two-thirds of inmates in NSW correctional facilities have a
      history of injection drug use, and about half have serological evidence of
      exposure to hepatitis C virus. The introduction of an accelerated hepatitis B
      vaccination program (0-1-2 months) in 1998, using a 20 microg/dose vaccine was
      necessitated by the need to vaccinate eligible inmates in this high-risk
      environment characterised by rapid client mobility. Since 1999, both 10 and 20
      microg doses of vaccine were introduced. We found that sero-response rates were
      not significantly influenced by HCV antibody status, but were significantly lower
      in cohorts of inmates vaccinated with the 10 microg dose of vaccine.

PMID- 11457552
TI  - Protection of chickens from lethal avian influenza A virus infection by live
      virus vaccination with infectious laryngotracheitis virus recombinants expressing
      the hemagglutinin (H5) gene.
AB  - The H5 hemagglutinin (HA) gene of a highly pathogenic avian influenza virus (AIV)
      isolate (A/chicken/Italy/8/98) was cloned and sequenced, and inserted at the non
      essential UL50 (dUTPase) gene locus of a virulent strain of infectious
      laryngotracheitis virus (ILTV). Northern and Western blot analyses of the
      obtained ILTV recombinants demonstrated stable expression of the HA gene under
      control of the human cytomegalovirus immediate-early gene promoter. In vitro
      replication of the HA-expressing ILTV mutants was not affected, and infection of
      chickens revealed a reduced but still considerable virulence, similar to that of
      a UL50 gene deletion mutant without foreign gene insertion. The immunized animals
      produced specific antibodies against ILTV and AIV HA, and were protected against
      challenge infections with either virulent ILTV, or two different highly
      pathogenic AIV strains (A/chicken/Italy/8/98, A/chicken/Scotland/59). After
      challenge, no ILTV could be reisolated from protected animals, and shedding of
      AIV was considerably reduced. Thus, although attenuation remains to be improved,
      genetically engineered ILTV live-virus vaccines might be used as vectors to
      protect chickens also against other pathogens.

PMID- 11457553
TI  - Reactogenicity of DTPa-HBV/Hib vaccine administered as a single injection vs DTPa
      HBV and Hib vaccines administered simultaneously at separate sites, to infants at
      2, 4 and 6 months of age.
AB  - An open, randomised, multicentre trial was performed to assess the reactogenicity
      and safety profile of the administration of a candidate Haemophilus influenzae
      type b (Hib) conjugate vaccine with a quadrivalent diphtheria-tetanus-acellular
      pertussis-hepatitis B (DTPa-HBV) vaccine as a single injection (Group 1) versus
      the simultaneous administration of the latter vaccine (DTPa-HBV) and an available
      Hib conjugate vaccine (Group 2) in opposite thighs, as a primary vaccination
      course to healthy infants at 2, 4 and 6 months of age. Eight hundred and eighty
      five infants (9.3+/-1.4 weeks old) were randomly allocated to Group 1 (n=665) and
      Group 2 (n=221). Oral polio vaccine was given concomitantly to all subjects.
      Blood samples (pre-vaccination and 1 month after the third dose) were obtained
      from a subset of infants (Group 1, 73; Group 2, 22) for serological
      determinations. Local and general symptoms were recorded by parents on diary
      cards. 2614 diary cards (Group 1, 1966; Group 2, 648) were collected. There were
      no statistically significant differences in the incidence of local and general
      symptoms between groups. Pain such that the infant cried when limb was moved was
      reported in 0.6 and 0.2% in groups 1 and 2, respectively. Redness and swelling
      (>20 mm in diameter) were recorded between 2.1 and 3% in both groups. Fussiness
      preventing normal activities was the most frequently reported general symptom in
      both groups (1.6 and 1.9% in groups 1 and 2, respectively). Fever (rectal
      temperature >39.5 degrees C) was reported in 0.4% (Group 1) and 0.3% (Group 2).
      All subjects included in the immunogenicity analysis had seroprotective or
      seropositive titres to the diphtheria, tetanus, hepatitis B and pertussis
      components of the vaccines. About 99 and 100% of infants had anti-PRP titres > or
      =0.15 mcg/ml in groups 1 and 2, respectively. This study indicates that DTPa-HBV
      vaccine given in a single injection with a candidate Hib conjugate vaccine has a
      similar reactogenicity profile to that of two commercially available vaccines
      (DTPa-HBV, Hib) given in two simultaneous injections to infants 2, 4 and 6 months
      of age.

PMID- 11457554
TI  - Modulation of the antibody response to the HIV envelope subunit by co
      administration of infectious or heat-inactivated canarypoxvirus (ALVAC)
      preparations.
AB  - Poxviruses are large DNA viruses capable of infecting a broad range of animal
      species. Infection is generally accompanied by an inflammatory response in the
      host, the extent of which varies considerably with the specific poxvirus and host
      species. Regarding ALVAC, a poxvirus derived from the canarypox vaccine strain,
      Kanapox, and which represents a promising immunization vehicle in humans, nothing
      is known about its inflammatory capacity. The present study was aimed at
      documenting this issue in rodents, including mice and guinea pigs. It was then
      attempted to evaluate how such properties could influence the immunogenicity of
      an antigen concomitantly administered with ALVAC preparations using the HIV
      envelope subunit, rgp160, as the model immunogen. The results revealed that
      ALVAC, either infectious or heat-inactivated, induced in both animal species an
      early inflammatory response, as evidenced by a rapid migration of neutrophils to
      the site of inoculation. In parallel, the canarypoxvirus was shown to strongly
      adjuvant the co-administered immunogen, resulting in a marked increase in Env
      specific IgG, IgG1 and particularly IgG2(a) serum titers. Of further interest,
      the heat-inactivated preparation of ALVAC retained this immunostimulatory
      activity. Whether or not a link between the inflammatory and immunomodulatory
      properties of ALVAC exists remains to be established, but such features are
      clearly interesting with respect to the potential use of ALVAC as an immunization
      vehicle.

PMID- 11457555
TI  - A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16
      (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity.
AB  - Vaccination with oncogene-derived DNA for anti-cancer treatment carries a risk of
      de-novo tumor induction triggered by the persisting recombinant DNA. We
      hypothesized that an oncoprotein whose primary sequence has been rearranged
      ('shuffled') to maintain all possible T cell epitopes still induces cytotoxic T
      cells against the authentic protein but is devoid of transforming properties. As
      a model antigen, we used the E7 oncoprotein of the human papillomavirus (HPV)
      type 16, the major cause of cervical cancer. We have generated an artificial E7
      molecule in which four domains were rearranged and, in order to maintain all
      possible T cell epitopes, certain sequences were duplicated. Upon transfection of
      this shuffled E7 gene (E7SH) into RMA cells, presentation of an E7 Db-restricted
      T cell epitope was shown by an E7-specific CTL line in vitro. Immunization of
      C57BL/6 mice with E7SH DNA induced E7-specific CTL and also conveyed protection
      against E7-positive syngeneic tumor cells. No transforming activity of E7SH DNA
      in NIH3T3 cells was detected, as determined by focus formation, induction of S
      phase under conditions of serum deprivation and degradation of endogenous pRB.
      Our results suggest that DNA shuffling may become a promising concept for DNA
      based anti-cancer vaccines.

PMID- 11457556
TI  - cDNA cloning, characterization and vaccine effect analysis of Haemaphysalis
      longicornis tick saliva proteins.
AB  - Immunological control of ticks is currently the only sustainable and practical
      alternative method to the current use of acaricides which has serious
      limitations. The success of this method is dependent upon identification and
      cloning of potential tick vaccine antigens. We used a combination of immuno
      screening of an adult tick cDNA library as well as the 3 and 5 rapid
      amplification of cDNA ends to clone two cDNAs, encoding tick saliva proteins from
      Haemaphysalis longicornis. The two cDNAs herein named HL 34 and 35 are 1000 bp
      each and encode polypeptides with 292 and 321 amino acid residues respectively.
      Northern blotting analysis of total RNA from ticks at different feeding stages
      revealed that expression of both HL 34 and HL35 mRNAs is induced during the slow
      feeding phase. We speculate that the functions of both genes are closely
      associated with blood feeding. Expression analysis by RT-PCR showed that both
      genes are expressed in other tick organs in addition to salivary glands.
      Recombinant HL 34 was successfully expressed in Escherichia coli and its
      suitability as a tick vaccine antigen was analyzed in rabbits. We propose that
      rHL34 could be a useful component of a cocktail tick vaccine.

PMID- 11457557
TI  - Protective CTL response is induced in the absence of CD4+ T cells and IFN-gamma
      by gene gun DNA vaccination with a minigene encoding a CTL epitope of Listeria
      monocytogenes.
AB  - Our work was undertaken to learn the mechanism of induction of protective
      cytotoxic T lymphocytes (CTL) by gene gun DNA vaccination with p91m encoding an H
      2Kd-restricted T cell epitope of listeriolysin O (LLO). Vaccination with p91m
      induced vigorous antigen-specific CD8+ CTL that produce IFN-gamma and was able to
      confer partial protection against listerial challenge. However, the p91m-induced
      protective immunity was revealed to be independent of the IFN-gamma and CD4+ T
      cell help. The CTL induction is also suggested to require neither adjuvant
      activity of the plasmid used nor IFN-gamma. The data may be feasible for the
      design of CTL inducing vaccines in various immunodeficiencies.

PMID- 11457558
TI  - Clinical and virological evaluation of the efficacy of an inactivated EHV1 and
      EHV4 whole virus vaccine (Duvaxyn EHV1,4). Vaccination/challenge experiments in
      foals and pregnant mares.
AB  - Pregnant mares and young foals were vaccinated with Duvaxyn EHV1,4, an
      inactivated and adjuvanted vaccine containing both the EHV-1 and 4 antigens. SN
      and CF antibody titres were induced two weeks after first vaccination. Antibody
      levels were boosted after second vaccination, however they never reached the
      levels induced after virus challenge. Young foals were challenged with virulent
      EHV-1 and EHV-4 field viruses. Pregnant mares were challenged with the highly
      abortigenic EHV-1 strain Ab4. Vaccinated animals showed a clear reduction in
      clinical signs and virus excretion compared to unvaccinated control animals. Log
      transformed antibody levels could be correlated to duration of virus excretion.
      The incidence of EHV-1 induced abortions was drastically reduced in vaccinated
      mares. Therefore, although vaccinated animals are not fully protected against
      disease, Duvaxyn EHV1,4 clearly reduces clinical symptoms, the duration of virus
      shedding and the quantity of virus shed. It can be concluded that vaccination of
      foals and pregnant mares with Duvaxyn EHV1,4 significantly reduces the risk of
      abortions and outbreaks of respiratory disease caused by circulating field
      viruses.

PMID- 11457559
TI  - The application of biodegradable collagen minipellets as vaccine delivery
      vehicles in mice and sheep.
AB  - Collagen minipellets are injectable delivery vehicles that release antigen and
      adjuvant over several days in a first-order release profile. In vaccination
      experiments in mice, secondary antibody responses induced by minipellets
      formulated with avidin and IL-1beta as adjuvant were equivalent to those induced
      by a conventional immunization with avidin in alum. When no adjuvant was used,
      anti-avidin responses induced by minipellets were 10-20-fold higher than those
      induced by injection of avidin in saline. In sheep, conventional vaccination with
      avidin in alum induced antibody responses initially exceeding that induced by
      minipellets formulated with avidin and IL-1beta, while following a secondary
      vaccination, the minipellet antibody response was equal to or greater than the
      alum-adjuvanted control groups. Increasing levels of IL-1beta adjuvant resulted
      in enhanced persistence of the antibody response. When clostridial vaccine
      antigens were incorporated into the minipellets, total antibody responses induced
      in sheep were equivalent to those induced by vaccination with the clostridial
      antigens in alum. Neutralizing antibody titres exceeded those induced by
      conventional vaccination. No adverse site reactions were observed at the implant
      site, with immunohistological study showing that the cellular infiltrate was
      dominated by a transient influx of neutrophils. This is a typical response to
      delivery of bioactive IL-1beta. The minipellets were completely degraded within
      35 days of implantation.

PMID- 11457560
TI  - A phase I clinical trial of a multi-epitope polypeptide TAB9 combined with
      Montanide ISA 720 adjuvant in non-HIV-1 infected human volunteers.
AB  - A phase I clinical trial was performed to examine the safety and immunogenicity
      of a multi-epitope polypeptide comprising the central 15 amino acids of the V3
      loop from six HIV-1 isolates. This protein called TAB9 was emulsified in
      Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0,
      0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males. Three immunisations
      were given at months 0, 1 and 6 in a randomised, double blind, placebo controlled
      clinical trial. The placebo was generally well tolerated. However, severe local
      reactions were observed in TAB9 vaccinated subjects after the second and third
      inoculations. Seven out of eight volunteers from the lower dose group showed
      moderate or severe local inflammation, while four out of eight subjects from the
      higher dose group developed granulomas and sterile abscesses. In general, the
      reactogenicity depended on the number of inoculations given and the dose of TAB9.
      Both doses were immunogenic, all immunised volunteers seroconverted and
      antibodies were broadly reactive against the V3 peptides included in the protein.
      All vaccine's sera reacted against gp120 in Western blot and 50% of them also
      neutralised at least one out of five laboratory isolates tested. No differences
      between doses were found. Anti TAB9 lymphoproliferative responses were observed,
      being more intense in the high dose group. Due to the strong local reactions that
      were found in this study, a change in the formulation will be required for
      further trials with this vaccine candidate in humans.

PMID- 11457561
TI  - Insulin-like growth factor I induced survival of axotomized olfactory neurons in
      the chick.
AB  - Insulin-like growth factor 1 (IGF1) receptor is expressed in avian olfactory
      neurons and IGF1 in the bulb. To explore the function of IGF1 in olfactory system
      in the chick, we infused IGF1 at the lesion site 0 and 12 h after olfactory
      axotomy. The animals were killed 1-3 days later. TdT mediated dUTP nick end
      labeling method and bromodeoxyuridine incorporation allowed the evaluation of
      programmed cell death and mitotic activity respectively in the olfactory
      epithelia of IGF1 treated or untreated lesioned animals and controls. IGF1
      treatment suppressed the apoptotic wave, stimulated mitosis which peaked within
      24 h (instead of 48 h), to return promptly to normal, and transiently maintained
      the number of calmodulin related kinase II expressing neurons at normal levels.
      It reveals a long lasting effect of IGF1 on the survival of lesioned olfactory
      neurons and transient effects on maintenance of differentiation and mitosis
      stimulation.

PMID- 11457562
TI  - Lipopolysaccharide stimulates norepinephrine efflux from the rat hypothalamus in
      vitro: blockade by soluble IL-1 receptor.
AB  - Lipopolysaccharide (LPS) has been shown to produce a number of central and
      neuroendocrine effects. While all mechanisms are not clear, it is believed that
      central catecholamines could be involved in this process. This study was done to
      investigate the direct effects of LPS on norepinephrine (NE) efflux from the
      medial basal hypothalamus in adult male rats using a combination of an in vitro
      incubation system and high performance liquid chromatography with electrochemical
      detection. Basal NE efflux was determined by incubating the hypothalami with
      Krebs Ringers Henseleit (KRH) alone for 60 min. Then, the hypothalami were
      incubated with KRH alone (control) or KRH containing 100 ng or 200 ng of LPS, 15
      microg of soluble IL-1 receptor (sIL-1R) or a combination of 200 ng LPS and 5 or
      15 microg of sIL-1R. In the third incubation period, the hypothalami were
      incubated with KRH alone to check for the residual effects of LPS if any. In the
      fourth incubation period, the hypothalami were incubated with high K+KRH to check
      for tissue viability. Incubation with LPS stimulated NE efflux in a dose
      dependent manner. Incubation of hypothalami with 200 ng of LPS and 15 microg of
      sIL-1R completely blocked LPS-induced increase in NE efflux. These results
      indicate that LPS could act directly on the hypothalamus to stimulate the efflux
      of NE and this effect is probably mediated through IL-1.

PMID- 11457563
TI  - Altered Glut4 mRNA levels in specific brain areas of hyperglycemic
      hyperinsulinemic rats.
AB  - The insulin sensitive glucose transporter Glut4 is expressed in neurons of the
      brain among which those of hypothalamic nuclei. It has been proposed that this
      transporter might be involved in the hypothalamic glucose-insulin sensing
      mechanism and thus in the nervous regulation of metabolism. In order to get
      further insights into its putative role, Glut4 expression was analyzed by
      quantitative competitive reverse transcription-polymerase chain reaction, in
      hypothalamic nuclei of hyperglycemic-hyperinsulinemic (HG-HI) rats, a model
      characterized by alteration of the autonomic nervous system activity. Glut4 mRNA
      content was decreased in the lateral hypothalamic area (33%) and arcuate nucleus
      (27%) but significantly only in the former. It was unchanged in other structures.
      These results are in favor of an alteration of Glut4 expression by short-term
      hyperglycemia and hyperinsulinemia that, in turn, could affect autonomic nervous
      system activity.

PMID- 11457564
TI  - 'In vivo perfusion Turnbull's reaction' for Fe(II) histochemistry in non
      anoxic/non-ischemic and anoxic/ischemic cat brains.
AB  - We developed a simple but ingenious histochemical method, 'in vivo perfusion
      Turnbull's reaction', for the visualization of non-heme Fe(II) of the brain; in
      situ release of Fe(2+) ions was coupled with formation of insoluble reaction
      product (Turnbull's blue) by in vivo perfusion of acid ferricyanide through the
      abdominal (non-anoxic/non-ischemic brain) or ascending (anoxic/ischemic brain)
      aorta in the deeply anesthetized adult cats. Frozen sections of the brain were
      treated according to the method of Nyguen-Legros et al. [12] to intensify
      Turnbull's reaction. The method revealed that cytoplasmic Fe(III) was reduced to
      Fe(II) in oligodendroglias in anoxic/ischemic (for 20 min) brains, and that
      Fe(II) was concentrated in the neuronal and glial cell nuclei regardless of the
      presence or absence of blood supply impairment.

PMID- 11457565
TI  - Strand scission in DNA induced by 5-hydroxytryptamine (serotonin) in the presence
      of copper ions.
AB  - It has been proposed that considerable DNA damage may be caused by endogenous
      metabolites produced during the body's normal metabolic processes. Several
      metabolites including L-3,4-dihydroxyphenylalanine and dopamine have been
      previously shown to lead to oxidative DNA breakage in the presence of copper
      ions. 5-hydroxytryptamine or serotonin is an important neurotransmitter in brain
      and spinal cord and is involved in the control of sleep and consciousness,
      aggression and mood. In this paper we show that serotonin is also capable of
      causing strand cleavage in DNA in the presence of Cu(II) through an oxidative
      mechanism. Serotonin reduces Cu(II) to Cu(I) which is accompanied by the
      generation of hydroxyl radical. Spectroscopic data indicate that serotonin is
      able to bind to DNA and copper ions. Relative DNA cleavage efficiency and copper
      binding ability of serotonin and structurally related molecules tryptophan and
      melatonin indicates that the phenolic group in serotonin is required for strand
      cleavage activity.

PMID- 11457566
TI  - Protective effect of tamoxifen on 1-methyl-4-phenylpyridine-induced hydroxyl
      radical generation in the rat striatum.
AB  - We examined whether tamoxifen could suppress 1-methyl-4-phenylpyridine (MPP(+))
      induced hydroxyl radical generation in the extracellular fluid of rat striatum,
      using in vivo microdialysis system. MPP(+) (5 mM) enhanced generation of hydroxyl
      radicals with concomitant increased efflux of dopamine. Tamoxifen (1--100 microM)
      dose-dependently suppressed the hydroxyl radical formation induced by MPP(+).
      Tamoxifen (100 microM) significantly attenuated dopamine efflux induced by
      MPP(+). The result in the present study is the first demonstration showing the
      protective effect of tamoxifen on hydroxyl radical generation induced by MPP(+)
      by suppressing dopamine efflux.

PMID- 11457567
TI  - Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and
      improves neurologic function in rats following middle cerebral artery occlusion.
AB  - Insulin-like growth factor-I (IGF-I) has been proposed as a treatment for stroke.
      However, it does not efficiently cross the blood-brain barrier (BBB).
      Intracerebroventricular injection of IGF-I has been shown to offer protection
      against cerebral ischemic damage in rats although this invasive method of
      administration may not be practical in humans. Non-invasive intranasal (IN)
      delivery of IGF-I to the brain is a promising alternative. We have assessed the
      therapeutic effect of IN IGF-I in rats following middle cerebral artery occlusion
      (MCAO). Treatment was initiated 10 min after the onset of MCAO and then again 24
      and 48 h later. Intranasal dosing of 75 microg IGF-1 (225 microg total IGF-I over
      48 h) significantly reduced corrected infarct volumes by 60% vs. control (P<0.01)
      and hemispheric swelling by 45.6% vs. control (P<0.05). Neurologic function,
      assessed by the postural reflex, flexor response and adhesive tape tests, was
      also improved by IN IGF-I as compared to control. Our study indicates IN delivery
      of IGF-1 holds significant promise as a non-invasive and efficacious method of
      bypassing the BBB for the treatment of stroke.

PMID- 11457568
TI  - A novel method for convenient assessment of arthritic pain in voluntarily walking
      rats.
AB  - Quantification of arthritic pain can be very useful in elucidating the mechanisms
      of arthritis and in assessing the effect of anti-arthritic medication or
      treatment. Here we report a novel method that allows convenient measurements of
      the severity of arthritic pain in voluntarily walking rats. We constructed a
      device to measure the weight load on each leg while the animal was walking
      through a path, the bottom of which was equipped with strain gauge weight
      sensors. Using this device, we measured the weight load on the right hind leg
      before and after induction of arthritis by carrageenan injection into the knee
      joint cavity of this leg. The carrageenan injection resulted in a significant
      reduction of weight load on the affected leg; the load decreased to the minimum
      level at 4 h after the injection and gradually returned to the pre-injection
      level by the fifth day. Intraperitoneal administration of morphine at 5.5 h after
      carrageenan injection could reverse the weight load change. These results suggest
      that our new device is an effective tool for convenient measurements of arthritic
      pain in dynamic conditions like walking.

PMID- 11457569
TI  - Changes in serotonin, dopamine and noradrenaline levels in striatum and nucleus
      accumbens after repeated administration of the abused drug MDMA in rats.
AB  - The selective neurotoxic action of the abused drug 3,4
      methylenedioxymethamphetamine (MDMA) on the serotonergic axons ascending from the
      dorsal raphe nucleus (DRN) is well known. The present study examined the long
      term effects of subchronic MDMA treatment on rat brain tissue contents of
      catecholaminergic neurotransmitters. Two and four weeks after cessation of
      repeated MDMA treatment (ten consecutive days, 20 mg/kg/day), the tissue
      neurotransmitter concentrations were measured by means of electrochemical
      detected HPLC in several forebrain areas and DRN. We found reduced serotonin
      levels in the whole forebrain at both instants of time. In nucleus accumbens
      (NAC), the noradrenaline levels were also decreased, whereas dopamine levels were
      increased 4 weeks after treatment. It is concluded that MDMA causes changes of
      monoamine transmitter levels outlasting cessation of drug intake for at least 4
      weeks. Decreased noradrenaline and/or serotonin may subsequently cause the
      augmentation of dopamine in NAC, a structure crucially involved in motivation
      circuits. With exception of transmitter alterations in the NAC, the post drug
      effects are opposite to the acute effects of MDMA and may underlie the
      psychiatric changes after MDMA intake in humans.

PMID- 11457570
TI  - Can vision compensate for a lower limbs muscular fatigue for controlling posture
      in humans?
AB  - The purpose of the present experiment was to investigate the effect of vision on
      postural control following a lower limbs muscular fatigue. Ten adult males were
      asked to maintain a single leg upright posture as immobile as possible in two
      conditions of no-fatigue and fatigue of the calf muscles. This muscles fatigue
      was achieved by standing on the toes until exhaustion. Within a trial, vision was
      suppressed or reinserted by eyes closure or opening. Center of foot pressure
      displacements were recorded using a force platform. Results showed that the
      availability of vision allowed the subjects to immediately cope with the
      destabilizing effect induced by muscular fatigue.

PMID- 11457571
TI  - Spatio-temporal source imaging reveals subcomponents of the human auditory
      mismatch negativity in the cingulum and right inferior temporal gyrus.
AB  - We investigated the generators of the mismatch negativity by means of spatio
      temporal source imaging on the basis of 64-channel electroencephalography data in
      order to study the time course and localization of proposed frontal sources.
      Results indicate that there are additional generators located both within the
      anterior cingulate gyrus and in the right inferior temporal gyrus, clearly
      separated from the supratemporal generators in space and time course. The
      cingulate generator is activated later than the temporal ones, which supports the
      hypothesis of a frontally located mechanism of involuntary switching of attention
      triggered by the temporal change detection system. Evidence for an additional
      right inferior temporal generator supports the hypothesis of right hemispheric
      dominance in early sound discrimination.

PMID- 11457572
TI  - Messenger RNA of steroid 21-hydroxylase (CYP21) is expressed in the human
      hippocampus.
AB  - 21-hydroxylase converts progesterone to 11-deoxycorticosterone and 17
      hydroxyprogesterone to 11-deoxycortisol, the substrates which are required for
      the production of the main adrenal steroids, corticosterone, aldosterone, and
      cortisol. As 21-hydroxylase activity has been detected in rodent and fetal human
      brain, we studied whether and to what extent 21-hydroxylase mRNA is expressed in
      hippocampal tissue specimens from patients undergoing epilepsy surgery (n=42). 21
      hydroxylase mRNA was detected in the hippocampus with an expression 10 000 times
      lower than in adrenal gland tissue. There was no significant difference in
      expression levels between women (9.5+/-2.7 arbitrary units (aU); mean+/-SEM) and
      men (8.0+/-2.2 aU); however, mRNA concentrations in the hippocampus of children
      (n=4, 1.8+/-0.5 aU) were considerably lower than in adults (n=38, 8.6+/-1.7 aU).
      The expression of 21-hydroxylase mRNA in the hippocampus suggests that this human
      brain area has the enzymatic capability to convert progesterone to 11
      deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol.

PMID- 11457573
TI  - Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an
      adrenocorticotropic hormone analog.
AB  - The proliferation, differentiation and survival of neuronal and glial cells are
      affected by a number of neurotrophic factors, such as nerve growth factor (NGF),
      brain-derived neurotrophic factor (BDNF) and others. In a previous study, we
      observed the effects of 'Semax' (Met-Glu-His-Phe-Pro-Gly-Pro), the
      physiologically active analogue of adrenocorticotropic hormone(4--10), on
      neuronal cell survival in vitro. We hypothesized that these effects may be
      mediated by the regulation of expression of some neurotrophic factors. To test
      this hypothesis we analyzed NGF and BDNF gene expression in glial cells obtained
      from the basal forebrain of newborn rats, following in vitro treatment with
      'Semax'. We observed changes in mRNA levels for both the NGF and BDNF genes. The
      greatest increase in expression was found after 30 min of 'Semax' administration.
      At this time, BDNF mRNA level was increased eight-fold in comparison with
      control, and NGF mRNA level was increased five-fold.

PMID- 11457574
TI  - Dorsolateral prefrontal cortex activation during automatic auditory duration
      mismatch processing in humans: a positron emission tomography study.
AB  - This study aimed to identify the neural networks underlying automatic and active
      auditory deviant detection in six healthy subjects using positron emission
      tomography. Eight alternating blocks of standard and standard plus duration
      deviant tones were presented while subjects performed a visual discrimination
      task. In an additional four blocks, the subjects then performed an auditory
      discrimination task on the deviant tones. Actively attending the deviant tones
      increased regional cerebral blood flow (rCBF) in the superior temporal and
      inferior frontal gyrus as well as in the superior and medio-frontal gyrus. When
      performing the visual task and presented with deviant tones, significant increase
      of rCBF was detected in the caudate nucleus, cerebellum, posterior cingulate,
      inferior frontal and pre-central gyrus thus indicating automatic extra-pyramidal
      processing of auditory duration deviants.

PMID- 11457575
TI  - Early emergence of temporal co-ordination of lower limb segments elevation angles
      in human locomotion.
AB  - We analysed the co-ordination of the elevation angles of the thigh (alpha(t)),
      shank (alpha(s)) and foot (alpha(f)) during walking in 19 adults and 21 children
      (aged 11--144 months), including the very first unsupported steps in four. Cross
      correlation functions (CCF) maturation of pairs of elevation angles was
      quantified by a global error parameter (Et((CCF))) reflecting the difference
      between particular CCF value of toddlers and mean adult value (Ea((CCF))). During
      the very first step, Et((CCF)) could be five times higher than Ea((CCF)). With
      walking experience, Et((CCF)) for both alpha(t)-alpha(s) and alpha(s)-alpha(f)
      pairs evolved following a biexponential profile, with a fast time constant below
      6 months. Adult-like CCF parameters were reached earlier for alpha(s)-alpha(f)
      than alpha(t)-alpha(s), indicating disto-proximal maturation of the temporal co
      ordination of the lower limb segments in human locomotion.

PMID- 11457576
TI  - Does body stability depend on postural chain mobility or stability area?
AB  - The purpose of this study was to examine whether postural stability depends only
      on the support base perimeter, that is the stability area, when body balance is
      perturbed by respiration. To this end, seven normal subjects were asked to
      breathe quietly, breathe deeply and to hold their breath (apnoea). They were
      asked to maintain a standing posture (Sta), and two sitting postures differing by
      the ischio femoral contact with the seat (Sit100 and Sit30). In other words,
      these three postures differed not only by the stability area, but also by pelvis
      mobility. The thoracic perimeter, displacement of the centre of pressure (CP) and
      iliac crest acceleration (Ah), taken as an index of pelvis mobility, of seven
      normal subjects were recorded. The results showed that the sway path (SP) was
      longer in seated subjects than in standing ones, and in Sit100 than in Sit30. The
      distance between the CP extreme positions (Delta Xp) varied in the opposite
      direction to SP. Iliac crests and thoracic displacements were shown to be in
      phase in Sit condition, and did not display any particular pattern in Sta. It was
      concluded that postural steadiness depends on the postural chain mobility in
      addition to stability area. As pelvis and lumbar column mobility are related, it
      is proposed that both contribute to postural chain mobility, owing to respiratory
      perturbation being compensated.

PMID- 11457577
TI  - Visceral antinociception produced by bee venom stimulation of the Zhongwan
      acupuncture point in mice: role of alpha(2) adrenoceptors.
AB  - The goal of the present study was to determine whether bee venom (BV) injection
      into the Zhongwan acupoint (CV12), compared to injection into a non-acupoint,
      produced antinociception in an acetic acid-induced visceral pain model. This was
      accomplished by injecting BV subcutaneously into the Zhongwan acupoint or into a
      non-acupoint 30 min before intraperitoneal injection of acetic acid in ICR mice.
      BV injection into the acupoint produced a dose dependent suppression of acetic
      acid-induced abdominal stretches and of acetic acid-induced Fos expression in the
      spinal cord and the nucleus tractus solitarii. In contrast BV injection into the
      non-acupoint only produced antinociception at the highest dose of BV tested.
      Naloxone pretreatment did not alter the antinociceptive effect of BV acupoint
      injection on the abdominal stretch reflex. On the other hand, pretreatment with
      the alpha 2-adrenoceptor antagonist, yohimbine completely blocked the
      antinociceptive effect of BV acupoint injection. These results imply that BV
      acupoint stimulation can produce visceral antinociception that is associated with
      activation of alpha 2-adrenoceptors, but not with naloxone-sensitive opioid
      receptors.

PMID- 11457578
TI  - Postnatal development of choline acetyltransferase activity in the rat
      laterodorsal tegmental nucleus.
AB  - Cholinergic neurons in the laterodorsal tegmental nucleus (LDT) have important
      roles in the regulation of sleep or waking in adult animals. In neonatal animals,
      sleep is largely occupied by paradoxical sleep. To investigate the relation
      between the cholinergic neurons in the LDT and the development of neonatal sleep,
      we dissected the LDT of rat by micropunch method at postnatal day 1--45 and
      measured the activity of choline acetyltransferase (ChAT). Either specific or
      total activity of ChAT was weak in the first week, increased strikingly in the
      second week and then moderately thereafter. The time course of the increase in
      ChAT activity correlates well to that of the decrease in the amount of
      paradoxical sleep or body twitches after birth.

PMID- 11457579
TI  - Conditioned place preference induced by the cannabinoid agonist CP 55,940:
      interaction with the opioid system.
AB  - Cannabinoids appear atypical as drugs of abuse since controversial data exist
      concerning the ability to lower the thresholds for electrical self-stimulation
      (Stark and Dews, 1980; Gardner et al., 1988; Gardner, 1992) and to support self
      administration (Martellotta et al., 1998; Tanda et al., 2000) or conditioned
      place preference in animals (Lepore et al., 1995; Parker and Gillies, 1995;
      McGregor et al., 1996; Sanudo-Pena et al., 1997; Chaperon et al., 1998; Hutcheson
      et al., 1998; Mallet and Beninger, 1998; Cheer et al., 2000; Valjent and
      Maldonado, 2000). Opioids and cannabinoids share some pharmacological properties
      (Manzanares et al., 1999). The most interactions were found in antinociception
      (Welch and Stevens, 1992; Smith et al., 1994) and, to a lesser extent, in drug
      reinforcement (Chen et al., 1990; Vela et al., 1995; Tanda et al., 1997). In the
      present study we asked whether: (1) a potent synthetic cannabinoid receptor
      agonist, [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptil)-phenyl]-trans-4-(3-hydroxy
      propyl) cyclohexanol] (CP 55,940) (from 10 to 40 microg/kg), which binds to the
      brain cannabinoid receptors with high affinity (Herkenham et al., 1991), would
      induce conditioned place preference, in comparison with heroin (from 0.1 to 5
      mg/kg); (2) what type of receptor was involved; (3) what kind of interaction
      there was between the two drugs, when given in combination, on reward. CP 55,940
      elicited a conditioned place preference only at a dose of 20 microg/kg similar in
      intensity to that of heroin (2 mg/kg). The reinforcing properties of the
      cannabinoid agonist were fully antagonised by pretreatment with the brain
      cannabinoid receptor-1 (CB(1)) antagonist, [N-piperidino-5-(4-chlorophenyl) 1
      (2,4-dichloro-phenyl)-4-methyl pyrazole-3-carboxamide hydrochloride] (SR 141716A)
      and naloxone. The combination of CP 55,940 and heroin, at the reinforcing doses,
      led to a reward which did not show any additive effect. Taken together these
      findings are important for understanding how the cannabinoids produce reward and
      the interconnection of the opioid and cannabinoid system in the motivation.

PMID- 11457580
TI  - Differential emotional experience induces elevated spine densities on basal
      dendrites of pyramidal neurons in the anterior cingulate cortex of Octodon degus.
AB  - It appears likely that, in analogy to the synaptic development of sensory and
      motor cortices, which critically depends on sensory or motor stimulation
      (Rosenzweig and Bennett, 1996), the synaptic development of limbic cortical
      regions are modulated by early postnatal cognitive and emotional experiences. The
      very first postnatal experience, which takes place in a confined and stable
      familial environment, is the interaction of the newborn individual with the
      parents and siblings (Gray, 1958). The aim of this quantitative morphological
      study was to analyze the impact of different degrees of juvenile emotional
      experience on the synaptic development in a limbic cortical area, the dorsal
      anterior cingulate cortex, a region which is involved in the perception and
      regulation of emotions. We study the precocious trumpet-tailed rat (Octodon
      degus) as the animal model, because, like human babies, this species is born with
      functional visual and acoustic systems and the pups are therefore capable of
      detecting even subtle environmental changes immediately after birth (Reynolds and
      Wright, 1979; Poeggel and Braun, 1996; Braun et al., 2000; Ovtscharoff and Braun,
      2001). The results demonstrate that already a subtle disturbance of the familial
      environment such as handling induced significantly elevated spine densities on
      the basal dendrites of layer III cortical pyramidal neurons. More severe
      disturbances of the emotional environment, such as periodic parental deprivation
      with or without subsequent chronic social isolation, resulted in an elevation of
      spine densities of similar magnitude as seen after handling and in addition,
      altered spine densities confined to specific dendritic segments were observed in
      these groups. These observations unveil the remarkable sensitivity of the dorsal
      anterior cingulate cortex towards environmental influences and behavioral
      experiences during phases of postnatal development. The behavioral consequences
      of these experience-induced synaptic changes still need to be analyzed further to
      assess if they are beneficial or detrimental to the animals cognitive and
      emotional capacities in later life.

PMID- 11457581
TI  - The differential expression patterns of messenger RNAs encoding K-Cl
      cotransporters (KCC1,2) and Na-K-2Cl cotransporter (NKCC1) in the rat nervous
      system.
AB  - Cation-chloride cotransporters have been considered to play pivotal roles in
      controlling intracellular and extracellular ionic environments of neurons and
      hence controlling neuronal function. We investigated the total distributions of K
      Cl cotransporter 1 (KCC1), KCC2 (KCC2), and Na-K-2Cl cotransporter 1 (NKCC1)
      messenger RNAs in the adult rat nervous system using in situ hybridization
      histochemistry. KCC2 messenger RNA was abundantly expressed in most neurons
      throughout the nervous system. However, we could not detect KCC2 messenger RNA
      expression in the dorsal root ganglion and mesencephalic trigeminal nucleus,
      where primary sensory neurons show depolarizing responses to GABA, suggesting
      that the absence of KCC2 is necessary for this phenomenon. Furthermore, KCC2
      messenger RNA was also not detected in the dorsolateral part of the
      paraventricular nucleus, dorsomedial part of the suprachiasmatic nucleus, and
      ventromedial part of the supraoptic nucleus where vasopressin neurons exist, and
      in the reticular thalamic nucleus. As vasopressin neurons in the suprachiasmatic
      nucleus and neurons in the reticular thalamic nucleus produce their intrinsic
      rhythmicity, the lack of KCC2 messenger RNA expression in these regions might be
      involved in the genesis of rhythmicity through the control of intracellular
      chloride concentration. The expression levels of KCC1 and NKCC1 messenger RNAs
      were relatively low, however, positive neurons were observed in several regions,
      including the olfactory bulb, hippocampus, and in the granular layer of the
      cerebellum. In addition, positive signals were seen in the non-neuronal cells,
      such as choroid plexus epithelial cells, glial cells, and ependymal cells,
      suggesting that KCC1 and NKCC1 messenger RNAs were widely expressed in both
      neuronal and non-neuronal cells in the nervous system. These results clearly
      indicate a wide area- and cell-specific variation of cation chloride
      cotransporters, emphasizing the central role of anionic homeostasis in neuronal
      function and communication.

PMID- 11457582
TI  - Relationship between metabolic dysfunctions, gene responses and delayed cell
      death after mild focal cerebral ischemia in mice.
AB  - The evolution of brain injury was examined in mice subjected to focal cerebral
      ischemia as induced by 30 min of intraluminar thread occlusion of the middle
      cerebral artery, followed by 3 h to 3 days of reperfusion. Metabolic dysfunctions
      were studied by 3H-leucine autoradiography for the measurement of cerebral
      protein synthesis and by regional ATP bioluminescent imaging. Metabolic changes
      were compared with responses of the genes c-fos, c-jun, heat-shock protein gene
      (hsp)72, p53-activated gene (pag)608 and caspase-3, which were investigated by in
      situ hybridization histochemistry and immunocytochemistry, and correlated with
      the degree of DNA fragmentation, as assessed by the terminal TdT-mediated dUTP
      biotin nick end labeling method. Intraluminar thread occlusion led to a
      reproducible reduction of cerebral laser Doppler flow to 20-30% of control.
      Thread withdrawal was followed by a short-lasting post-ischemic hyperperfusion to
      approximately 120%. In non-ischemic control animals, fractional protein synthesis
      values of 0.81+/-0.26 and 0.94+/-0.23 were obtained. Thread occlusion resulted in
      a suppression of protein synthesis throughout the territory of the middle
      cerebral artery after 3 h of reperfusion (0.04+/-0.08 in caudate-putamen and
      0.14+/-0.19 in somatosensory cortex, P<0.05). Protein synthesis partly recovered
      in the cortex after 24 h and 3 days (0.71+/-0.40 and 0.63+/-0.26, respectively),
      but remained suppressed in the caudate-putamen (0.14+/-0.22 and 0.28+/-0.28).
      Regional ATP levels did not show any major disturbances at the reperfusion times
      examined. Thread occlusion resulted in a transient increase of c-fos mRNA levels
      in ischemic and non-ischemic parts of the cortex and caudate-putamen at 3 h after
      ischemia, which suggests that spreading depressions were elicited in the tissue.
      At the same time, c-jun and hsp72 mRNAs were elevated only in ischemic brain
      areas showing inhibition of protein synthesis. C-fos and c-jun responses
      completely disappeared within 24 h of reperfusion. Hsp72 mRNA levels remained
      elevated in the cortex after 24 h, but decreased to basal values in the caudate
      putamen. Twenty-four hours after reperfusion, pag608 and caspase-3 mRNA levels
      increased in the caudate-putamen, where protein synthesis rates were still
      reduced, and remained elevated even after 3 days. However, pag608 and caspase-3
      mRNA levels did not increase in the cortex, where protein synthesis recovered.
      After 24 h and 3 days, functionally active p20 fragment of caspase-3 was detected
      in the caudate-putamen, closely associated with the appearance of DNA fragmented
      cells. Neither activated caspase-3 nor DNA fragmentation were noticed in the
      cortex.In summary, the suppression of protein synthesis is reversible in the
      ischemia-resistant cortex following 30 min of thread occlusion in mice, but
      persists in the vulnerable caudate-putamen. In the caudate-putamen, apoptotic
      programs are induced, closely in parallel with the manifestation of delayed cell
      death. Thus, the recovery of protein synthesis may be a major factor influencing
      tissue survival after transient focal ischemia.

PMID- 11457583
TI  - Nisoxetine infusion into the olfactory bulb enhances the capacity for male rats
      to identify conspecifics.
AB  - In the present report, the norepinephrine uptake inhibitor nisoxetine as well as
      a cocktail of nisoxetine and the alpha-adrenergic receptor antagonist
      phentolamine were infused unilaterally into the olfactory bulb during
      microdialysis to assess their effects upon the capacity of male rats to identify
      conspecifics. A social discrimination test was conducted while simultaneously
      measuring olfactory bulb norepinephrine output in the dialysate before, during,
      and after behavioral testing. Nisoxetine significantly increased norepinephrine
      levels in the olfactory bulb compared with the Ringer's solution control group.
      Following such increases in olfactory bulb norepinephrine, identification
      responses were enhanced compared with that observed in the Ringer's control. In
      the presence of phentolamine, nisoxetine elevated olfactory bulb norepinephrine
      to levels similar to that obtained in the nisoxetine alone group, however,
      investigatory responses directed to the conspecifics indicated an absence of
      identification capacity similar to that observed in the Ringer's control group.
      These results reveal a direct link between norepinephrine transmission in the
      olfactory bulb and enhanced identification via its activation of postsynaptic
      alpha-adrenergic receptors. These results also show that inhibition of
      norepinephrine uptake may represent an important mechanism involved with the
      enhancement of social identification and suggest a possible novel effect for the
      antidepressant nisoxetine.

PMID- 11457584
TI  - Neither perirhinal/entorhinal nor hippocampal lesions impair short-term auditory
      recognition memory in dogs.
AB  - Visual, tactile, and olfactory recognition memory in animals is mediated in part
      by the perirhinal/entorhinal (or rhinal) cortices and, possibly, the hippocampus.
      To examine the role of these structures in auditory memory, we performed rhinal,
      hippocampal, and combined lesions in groups of dogs trained in auditory delayed
      matching-to-sample with trial-unique sounds. The sample sound was presented
      through a central speaker and, after a delay, the sample sound and a different
      sound were played alternately through speakers placed on either side of the
      animal; the animal was rewarded for responding to the side emitting the sample
      sound. None of the lesion groups showed significant impairment in comparison
      either to their own preoperative performance or to the performance of intact
      control dogs. This was the case both for relearning the delayed matching rule at
      a delay of 1.5 s and for task performance at variable delays ranging from 10 to
      90 s. From these findings we suggest that the tissue critical for auditory
      recognition memory is located outside both the perirhinal/entorhinal cortices and
      the hippocampus.

PMID- 11457585
TI  - The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical
      characterization of hippocampal cell populations and pilocarpine-induced changes.
AB  - At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine
      administration to the tropical rodent Proechimys guyannensis (casiragua) elicited
      an acute seizure that did not develop in long-lasting status epilepticus and was
      not followed by spontaneous seizures up to 30 days, when the hippocampus was
      investigated in treated and control animals. Nissl staining revealed in
      Proechimys a highly developed hippocampus, with thick hippocampal commissures and
      continuity of the rostral dentate gyri at the midline. Immunohistochemistry was
      used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid
      decarboxylase, and nitric oxide synthase expression. The latter was also
      investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric
      evaluation with image analysis were performed. Differences, such as low calbindin
      immunoreactivity confined to some pyramidal cells, were found in the normal
      Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated
      casiraguas, stereological cell counts in Nissl-stained sections did not reveal
      significant neuronal loss in hippocampal subfields, where the examined markers
      exhibited instead striking changes. Calbindin was induced in pyramidal and
      granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide
      synthase-containing interneurons and their staining intensity were significantly
      increased. Glutamic acid decarboxylase(67)-immunoreactive interneurons increased
      markedly in the hilus and decreased in the CA1 pyramidal layer. The number and
      staining intensity of calretinin-immunoreactive pyramidal cells and interneurons
      were significantly reduced. These findings provide the first description of the
      Proechimys hippocampus and reveal marked long-term variations in protein
      expression after an epileptic insult, which could reflect adaptive changes in
      functional hippocampal circuits implicated in resistance to limbic epilepsy.

PMID- 11457586
TI  - Drastic neuronal loss in vivo by beta-amyloid racemized at Ser(26) residue:
      conversion of non-toxic [D-Ser(26)]beta-amyloid 1-40 to toxic and proteinase
      resistant fragments.
AB  - It is unclear how and when insoluble beta-amyloid in senile plaques exerts
      degenerative effects on distant hippocampal neurons in Alzheimer's disease.
      Racemization of Ser and Asp residues of insoluble beta-amyloid is a typical age
      dependent process. In this study, we investigated the fibril formation activity
      and cytotoxic activity of beta-amyloid 1-40 racemized at the Asp or Ser residue.
      In contrast to beta-amyloid 1-40 and its derivative substituted with the D-Asp(1,
      7 or 23) or D-Ser(8) residue, [D-Ser(26)]beta-amyloid 1-40 was non-toxic to PC12
      cells, and did not exhibit significant fibril formation activity making it
      soluble. However, [D-Ser(26)]beta-amyloid 1-40, but not beta-amyloid 1-40, was
      converted in vitro to a potent neurotoxic and truncated peptide, [D-Ser(26)]beta
      amyloid 25-35 or [D-Ser(26)]beta-amyloid 25-40, by chymotrypsin-like enzymes and
      aminopeptidase M. Soluble [D-Ser(26)]beta-amyloid 1-40 was injected into rat
      hippocampus with a non-toxic dose of ibotenic acid, an excitatory amino acid.
      Nissl staining and microtubule-associated protein-2 immunostaining revealed that
      [D-Ser(26)]beta-amyloid 1-40, as well as [D-Ser(26)]beta-amyloid 25-35, produced
      a drastic degeneration of the CA1 neurons with ibotenic acid although [D
      Ser(26)]beta-amyloid 1-40 alone or ibotenic acid alone did not exert neuronal
      damage. This suggests the in vivo conversion of non-toxic [D-Ser(26)]beta-amyloid
      1-40 to the toxic and truncated peptides which enhance the susceptibility of
      neurons to the excitatory amino acid.These results and the presence of [D
      Ser(26)]beta-amyloid 25-35-like antigens in Alzheimer's disease brains suggest
      that soluble [D-Ser(26)]beta-amyloid 1-40, possibly formed during the aging
      process, is released from senile plaques, and converted by brain proteinases to
      truncated [D-Ser(26)]beta-amyloid 25-35(40)-like peptides, which degenerate
      hippocampal neurons by enhancing the susceptibility to excitatory amino acids in
      Alzheimer's disease brains. These findings may provide the basis for a new
      therapeutic approach to prevent the neurodegeneration in Alzheimer's disease.

PMID- 11457587
TI  - Electrotonic profile and passive propagation of synaptic potentials in three
      subpopulations of hippocampal CA1 interneurons.
AB  - To elucidate the role of dendritic morphology in signal transfer, the passive
      propagation of somatic and dendritic potentials was compared in multi-compartment
      models of three interneuron subpopulations in the CA1 region. Nine calbindin-, 15
      calretinin- and 10 parvalbumin-containing cells were modelled incorporating the
      detailed geometry, the currents of the action potentials in the soma, and the
      AMPA, N-methyl-D-aspartate and GABA-B receptor-mediated postsynaptic currents in
      the dendrites. The cable properties show characteristic differences among the
      subpopulations. The morphotonic length of calbindin and calretinin cell dendrites
      is larger than of parvalbumin cells. Thus parvalbumin cells are more compact than
      calbindin or calretinin cells unless the ratio of their axial and membrane
      resistivities exceeds the ratios of the other two cell types by more than 33%. In
      calbindin cells, the distal parts of the extremely long dendrites that invade the
      alveus are virtually isolated from the soma for passively propagating signals.
      The synaptic potentials evoked at a given morphotonic distance from the soma show
      larger differences locally on the dendrites than on the soma in all
      subpopulations. Both the somatic and dendritic amplitude ratios are the smallest
      in PV cells. In calbindin cells the somatic amplitude of synaptic potentials
      evoked at the same morphotonic distance from the soma is similar regardless of
      the number of branchpoints along their path. In calretinin and parvalbumin cells,
      from dendrites with long primary segments synaptic potentials reach the soma with
      larger amplitude than from dendrites that are branching close to the soma. The
      dendrites with the larger impact on somatic membrane potential are usually the
      dendrites that enter the stratum lacunosum-moleculare. These results indicate
      that dendritic morphology plays a role in changing the effectiveness of synaptic
      potentials evoked at different dendritic locations, and in this way is likely to
      be an important factor in determining the integrative properties of the different
      neuron populations.

PMID- 11457588
TI  - The interaction of visual and proprioceptive inputs in pointing to actual and
      remembered targets in Parkinson's disease.
AB  - We previously reported that Parkinson's disease patients could point with their
      eyes closed as accurately as normal subjects to targets in three-dimensional
      space that were initially presented with full vision. We have now further
      restricted visual information in order to more closely examine the individual and
      combined influences of visual information, proprioceptive feedback, and spatial
      working memory on the accuracy of Parkinson's disease patients. All trials were
      performed in the dark. A robot arm presented a target illuminated by a light
      emitting diode at one of five randomly selected points composing a pyramidal
      array. Subjects attempted to "touch" the target location with their right finger
      in one smooth movement in three conditions: dark, no illumination of arm or
      target during movement; movement was to the remembered target location after the
      robot arm retracted; finger, a light-emitting diode on the pointing fingertip was
      visible during the movement but the target was extinguished; again, movement was
      to the remembered target location; and target, the target light-emitting diode
      remained in place and visible throughout the trial but there was no vision of the
      arm. In the finger condition, there is no need to use visual-proprioceptive
      integration, since the continuously visualized fingertip position can be compared
      to the remembered location of the visual target. In the target condition, the
      subject must integrate the current visible target with arm proprioception, while
      in the dark condition, the subject must integrate current proprioception from the
      arm with the remembered visual target. Parkinson's disease patients were
      significantly less accurate than controls in both the dark and target conditions,
      but as accurate as controls in the finger condition. Parkinson's disease
      patients, therefore, were selectively impaired in those conditions (target and
      dark) which required integration of visual and proprioceptive information in
      order to achieve accurate movements. In contrast, the patients' normal accuracy
      in the finger condition indicates that they had no substantial deficits in their
      relevant spatial working memory. Final arm configurations were significantly
      different in the two subject groups in all three conditions, even in the finger
      condition where mean movement endpoints were not significantly different.
      Variability of the movement endpoints was uniformly increased in Parkinson's
      disease patients across all three conditions. The current study supports an
      important role for the basal ganglia in the integration of proprioceptive signals
      with concurrent or remembered visual information that is needed to guide
      movements. This role can explain much of the patients' dependence on visual
      information for accuracy in targeted movements. It also underlines what may be an
      essential contribution of the basal ganglia to movement, the integration of
      afferent information that is initially processed through multiple, discrete
      modality-specific pathways, but which must be combined into a unified and
      continuously updated spatial model for effective, accurate movement.

PMID- 11457589
TI  - Expression and function of glycine receptors in striatal cholinergic interneurons
      from rat and mouse.
AB  - Although glycine receptors are widely expressed in the forebrain their function
      is obscure. We studied their activation by two possible endogenous ligands,
      glycine and taurine, and demonstrate a different expression pattern of glycine
      receptors in neostriatal cholinergic interneurons from two rodent species. Single
      cell-reverse transcription-polymerase chain reaction analysis of glycine receptor
      subunit expression was combined with whole-cell recordings from acutely isolated
      cholinergic interneurons. All cells expressed the alpha2-glycine receptor
      subunit, the majority (72%) in mice but none in young and aged rats expressed the
      alpha3-subunit. The beta-subunit expression was associated with both a higher
      efficacy and a higher potency of the partial agonist taurine. Cells expressing
      the alpha3-subunit displayed a slower desensitization of taurine responses than
      of glycine responses, in contrast to cells expressing the alpha2-, beta-subunits
      where desensitization time constants were similar. Glycine responses were reduced
      by preapplication of taurine; this effect was more pronounced in cells lacking
      the alpha3-subunit. We demonstrate interspecies differences and heterogeneity in
      expression and function of glycine receptors within the same neuronal population
      in the neostriatum.

PMID- 11457590
TI  - Distinct muscarinic receptors enhance spontaneous GABA release and inhibit
      electrically evoked GABAergic synaptic transmission in the chick lateral
      spiriform nucleus.
AB  - The effects of muscarinic agonists on GABAergic synaptic transmission were
      examined using whole-cell patch-clamp recording in chick brain slices containing
      the lateral spiriform nucleus. Bath application of muscarine (10 microM) both
      increased the frequency of spontaneous GABAergic postsynaptic currents and
      reduced the amplitude of evoked GABAergic polysynaptic postsynaptic currents
      elicited by focal afferent fiber electrical stimulation. Both of these muscarinic
      actions were reversible and dose-dependent. Two M(1) antagonists, telenzepine and
      pirenzipine, and to a lesser extent the M(2) antagonist methoctramine, protected
      against muscarine's inhibition of the evoked polysynaptic currents. Other M(2)
      antagonists (tripitramine and gallamine) as well as the M(3) antagonist 4-DAMP
      mustard (4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride) and an
      M(4) antagonist (tropicamide) provided little or no protection against muscarine
      in this assay. In contrast, 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine
      hydrochloride, tropicamide and telenzepine, but not pirenzepine, methoctramine,
      tripitramine and gallamine, blocked muscarine's enhancement of spontaneous
      GABAergic currents. McN-A-343 [(4-hydroxy-2-butynyl)-1-trimethylammonium-m
      chlorocarbanilate chloride] and CDD-0097 (5-propargyloxycarbonyl-1,4,5,6
      tetrahydropyrimidine hydrochloride), two M(1) agonists, mimicked muscarine's
      inhibition of the evoked polysynaptic GABAergic currents but did not mimic
      muscarine's enhancement of spontaneous GABAergic currents. Both actions of
      muscarine persisted when slices were pretreated with pertussis toxin or N
      ethylmaleimide, which inactivate G-proteins coupled to M(2) and M(4) receptors
      while leaving G-proteins coupled to M(1), M(3) and M(5) receptors intact.
      Muscarine had no significant effect on the amplitude of the direct postsynaptic
      current elicited by exogenous GABA in the presence of tetrodotoxin. The results
      demonstrate that distinct muscarinic receptors oppositely modulate GABAergic
      transmission in the lateral spiriform nucleus. The receptor mediating the
      inhibition of evoked GABAergic polysynaptic currents is pharmacologically similar
      to an M(1) receptor, while the enhancement of spontaneous GABAergic currents
      appears to be mediated by an M(3) receptor.

PMID- 11457591
TI  - Monoaminergic innervation of the macaque extended amygdala.
AB  - The extended amygdala is a group of structures including the central and medial
      amygdaloid nuclei, bed nucleus of the stria terminalis, and sublenticular
      substantia innominata. This group of structures is thought to be important in a
      variety of psychiatric disorders, many of which are linked in one way or another
      to monoamines and their transporters. However, not much is known about the
      distribution of these molecules in the primate extended amygdala. Thus, we mapped
      the distribution of fibers immunoreactive for tyrosine hydroxylase, dopamine beta
      hydroxylase, serotonin, dopamine transporter, and serotonin transporter in the
      brains of macaque monkeys. Tyrosine hydroxylase-, serotonin-, and serotonin
      transporter-immunoreactive fibers were found in highest concentrations in the
      lateral division of the central nucleus and lateral dorsal part of the bed
      nucleus of the stria terminalis. Dopamine beta-hydroxylase-immunoreactive fibers
      were found in the highest concentration in the lateral ventral bed nucleus of the
      stria terminalis. Dopamine transporter-immunoreactive fibers were found in the
      highest concentrations in the lateral juxtacapsular and lateral dorsal capsular
      subnuclei of the bed nucleus and lateral capsular subnucleus of the central
      amygdaloid nucleus, though in much lower amounts than was present in the
      striatum. These results suggest prominent roles for these transmitters,
      particularly in the lateral dorsal bed nucleus and lateral part of the central
      nucleus. The relative absence of dopamine transporter in the extended amygdala
      suggests that this transmitter acts more through volume transmission while
      serotonin, which is generally accompanied by proportionate amounts of
      transporter, may act more like a classical neurotransmitter. In addition, the
      finding of heavy concentrations of dopamine- and serotonin-immunoreactive fibers
      in the lateral central nucleus and lateral dorsal bed nucleus lends further
      support to the idea of these areas as parallels in some respects to the striatum.

PMID- 11457592
TI  - "When a rat smells a cat": the distribution of Fos immunoreactivity in rat brain
      following exposure to a predatory odor.
AB  - Wistar rats were exposed to a fabric collar that had been worn by a domestic cat.
      Exposure took place in an open rectangular arena containing a small wooden "hide
      box". Rats exposed to cat odor spent more than 87% of their time in the hide box
      during a single 20-min exposure session, whereas rats exposed to a control odor
      (an unworn collar) spent less than 20% of their time hiding. One hour following
      this session, rats were killed and Fos immunoreactivity was compared between cat
      odor-exposed rats, control odor-exposed rats and an additional group that had
      remained in their home cages. Cat odor-exposed rats showed greater Fos expression
      than controls in many brain regions, particularly in the medial amygdala, medial
      hypothalamus and periaqueductal gray. Significant findings included strong and
      selective induction of Fos in the posteroventral medial amygdaloid nucleus, the
      premamillary nucleus (dorsal part), ventromedial hypothalamic nucleus
      (dorsomedial part), dorsomedial hypothalamic nucleus, periaqueductal gray
      (dorsomedial, dorsolateral and ventrolateral parts) and the cuneiform nucleus.
      Robust Fos expression in the ventromedial hypothalamus, premamillary nucleus and
      periaqueductal gray confirms previous suggestions of a role for these areas in
      predator-induced defensive behavior. Fos immunoreactivity in the medial, but not
      central or basolateral amygdala is a novel finding and draws attention to this
      subregion as a possible interface between olfactory input and emotional output.

PMID- 11457593
TI  - Sex differences in the brain of goldfish: gonadotropin-releasing hormone and
      vasotocinergic neurons.
AB  - The differences between male and female behaviors are reflected in sexual
      dimorphism of brain structures and are found throughout the nervous system in a
      variety of vertebrates. The present study examined neurons immunolabeled for
      gonadotropin-releasing hormone and arginine vasotocin in the brain of the
      goldfish Carassius auratus to determine if these neurons are sexually dimorphic.
      There was no sex difference or influence of sex steroids on the neuronal volume
      and optical density of staining of arginine vasotocin neurons. Similarly,
      gonadotropin-releasing hormone neurons of the terminal nerve and midbrain
      tegmentum did not differ between sexually mature males, females and maturing
      females replaced with sex steroids with respect to distribution, numbers, optical
      density of staining, or gross morphology. In maturing females, testosterone
      specifically recruited additional preoptic gonadotropin-releasing hormone neurons
      to equal those in sexually mature individuals. Since estrogen had no effect, the
      influence of testosterone on gonadotropin-releasing hormone neuronal numbers
      appears to be independent of aromatization. Specifically, the preoptic
      gonadotropin-releasing hormone neuronal size was significantly larger in sexually
      mature males than females. 11-Ketotestosterone-replacement to ovariectomized
      maturing females induced male-typical secondary characters and male-type
      courtship behavior but did not masculinize the preoptic gonadotropin-releasing
      hormone neuronal size. Our results show that the sexually dimorphic preoptic
      gonadotropin-releasing hormone neuronal size is determined by factors (genetic)
      other than gonadal steroids. Further, we propose the hypothesis that phenotypic
      and behavioral sex differences need not be accompanied by structural differences
      in gonadotropin-releasing hormone and arginine vasotocin in the brain.

PMID- 11457594
TI  - Hypothalamic leptin resistance is associated with impaired leptin signal
      transduction in aged obese rats.
AB  - Leptin contributes to the regulation of both food intake and energy expenditure.
      We previously demonstrated that the F344xBN rat, a rodent model for late-onset
      obesity, is leptin-resistant and that leptin signal transduction following
      peripheral administration of leptin is impaired in these aged, overweight rats.
      To determine if leptin signal transduction is impaired in response to central
      administration of leptin and whether reduced hypothalamic leptin receptors may be
      contributing to the impaired signal transduction, we examined the in vivo dose
      response leptin-induced STAT3 activation (phosphorylation and binding activity to
      the SIE M67 oligonucleotide) in response to i.c.v. administration of leptin along
      with the level of hypothalamic leptin receptor protein in young and older, late
      onset obese rats. The leptin-induced maximum phosphorylation of STAT3 was 41%
      greater in young compared with older obese rats, but the dose required for half
      maximal phosphorylation of STAT3 was similar in both the young (41 ng) and old
      obese (47 ng) rats. There were no changes in total STAT3 protein with leptin or
      age, and leptin did not increase phosphorylation of STAT1. Leptin increased
      phosphorylation of STAT3 transcription factor binding eight-fold in the young but
      only four-fold in the aged-obese rats, and leptin receptor protein was 50%
      greater in the young compared with aged rats. These data indicate that aged
      overweight rats demonstrate reduced signal transduction in response to centrally
      administered leptin that may be the result of the diminished leptin receptor
      protein observed in the aged-obese rats. The diminished leptin receptors and
      impaired leptin signal transduction may explain the diminished physiological
      responses observed following leptin administration in older rats. This impaired
      leptin signal transduction may be due either to the elevated obesity with age or
      to age itself, or to both.

PMID- 11457595
TI  - Altered content and modulation of soluble guanylate cyclase in the cerebellum of
      rats with portacaval anastomosis.
AB  - It is shown that the glutamate-NO-cGMP pathway is impaired in cerebellum of rats
      with portacaval anastomosis in vivo as assessed by in vivo brain microdialysis in
      freely moving rats. NMDA-induced increase in extracellular cGMP in the cerebellum
      was significantly reduced (by 27%) in rats with portacaval anastomosis.
      Activation of soluble guanylate cyclase by the NO-generating agent S-nitroso-N
      acetyl-penicillamine and by the NO-independent activator YC-1 was also
      significantly reduced (by 35-40%), indicating that portacaval anastomosis leads
      to remarkable alterations in the modulation of guanylate cyclase in cerebellum.
      Moreover, the content of soluble guanylate cyclase was increased ca. two-fold in
      the cerebellum of rats with portacaval anastomosis. Activation of soluble
      guanylate cyclase by NO was higher in lymphocytes isolated from rats with
      portacaval anastomosis (3.3-fold) than in lymphocytes from control rats (2.1
      fold). The results reported show that the content and modulation of soluble
      guanylate cyclase are altered in brain of rats with hepatic failure, resulting in
      altered function of the glutamate-NO-cGMP pathway in the rat in vivo. This may
      lead to alterations in cerebral processes such as intercellular communication,
      circadian rhythms, including the sleep-waking cycle, long-term potentiation, and
      some forms of learning and memory.

PMID- 11457596
TI  - Postnatal differentiation of unipolar brush cells and mossy fiber-unipolar brush
      cell synapses in rat cerebellum.
AB  - The unipolar brush cells are excitatory, cerebellar granular layer interneurons
      that receive mossy fiber input on their dendritic brushes in the form of a giant
      glutamatergic synapse. We investigated the postnatal development of the brush of
      the unipolar brush cell in lobules IX and X by light microscopy and defined the
      maturation of mossy fiber-unipolar brush cell synapses and mossy fiber-granule
      cell synapses by electron microscopy using calretinin immunocytochemistry to
      identify unipolar brush cells. During the first postnatal week, unipolar brush
      cells possessed one or two short, branched dendrites. The brush differentiated
      primarily during the successive 21 postnatal (P) days, during which it underwent
      progressive maturation. This developmental process was subdivided into stages 1
      4, which were descriptively termed protodendritic unipolar brush cell (P2-12),
      filopodial brush (P12-16), intermediate brush (P16-21), and dendriolar brush (P21
      28) stages. Electron microscopic measurements of individual mossy fiber-unipolar
      brush cell and mossy fiber-granule cell synaptic junctions were made at P12, 16,
      21, and 28. While the average length of mossy fiber-unipolar brush cell synapses
      increased during development, that of mossy fiber-granule cell synapses
      decreased. Comparisons of the lengths of mossy fiber-unipolar brush cell and
      mossy fiber-granule cell synapses demonstrated that mossy fiber-unipolar brush
      cell synapses were longer on average than mossy fiber-granule cell synapses for
      all ages. Frequency distribution histograms also showed that the percentage of
      mossy fiber-unipolar brush cell synapses longer than 0.5 microm was lower in the
      pooled P12-P16 groups than in the pooled P21-P28 groups (8 versus 20%). In
      contrast, mossy fiber-granule cell synapses longer than 0.5 microm were a small
      minority at P12, 16, and 21, and occurred rarely at P28. The present study
      indicates that mossy fiber-unipolar brush cell synapses increase in length with
      the differentiation of the brush dendrioles, while that of mossy fiber-granule
      cell synapses decrease with differentiation of the granule cell dendritic claws.
      The finding that mossy fiber-unipolar brush cell synapses were generally longer
      than mossy fiber-granule cell synapses may indicate that the properties of the
      postsynaptic targets play a major role in shaping synaptic appositions within
      cerebellar glomeruli.

PMID- 11457597
TI  - Differentiation of presumed serotonergic dorsal raphe neurons in relation to
      behavior and wake-sleep states.
AB  - Using extracellular single unit recording, either alone or in combination with
      microdialysis application of drugs, we examined the characteristics of presumed
      serotonergic dorsal raphe neurons during wake-sleep states in the freely moving
      cat. Recordings were made from a total of 272 neurons in the dorsal raphe
      nucleus. Of these, 240 (88%) were classified as serotonergic on the basis of
      their typical long-duration action potential, slow discharge activity, and
      reduced spontaneous discharge rate during paradoxical sleep compared to during
      slow-wave sleep. An inhibitory response to serotonergic agonists and a slow
      conduction velocity were seen in all neurons of this type tested or identified by
      stimulation of the main ascending serotonergic pathway. These presumed
      serotonergic dorsal raphe neurons could be subdivided into two typical previously
      identified groups (types I-A and I-B) and four atypical new groups (types I-C, II
      A, II-B, and II-C) according to differences in firing patterns during wake-sleep
      states. The typical neurons were evenly distributed in the dorsal raphe nucleus
      and their activity was related to the level of behavioral arousal, since they
      discharged regularly at a high rate during waking and at progressively slower
      rates during slow-wave sleep, and ceased firing either during slow-wave sleep
      with ponto-geniculo-occipital waves and paradoxical sleep (type I-A) or only
      during paradoxical sleep (type I-B). In contrast, the atypical subgroups were
      unevenly distributed in the dorsal raphe nucleus and exhibited firing patterns
      distinct from those of the typical neurons, such as sustained tonic activity
      during paradoxical sleep (types I-C and II-C) or showing their highest rate of
      tonic discharge during slow-wave sleep, with suppression of discharge during both
      waking and paradoxical sleep (type II-B). From these data we suggest that
      presumed serotonergic dorsal raphe neurons play different roles in behavioral
      state control and that there is functional topographic organization in the dorsal
      raphe nucleus.

PMID- 11457598
TI  - Activation of protein kinase C increases acetylcholine release from frog motor
      nerves by a direct action on L-type Ca(2+) channels and apparently not by
      depolarisation of the terminal.
AB  - The effects of the dihydropyridine Ca(2+) channel antagonist nimodipine and the
      protein kinase C inhibitors staurosporine and calphostin C on the changes in the
      electrophysiological indices of quantal acetylcholine release induced by a 4-beta
      phorbol ester were studied at the frog neuromuscular junction. 4-beta-Phorbol 12
      myristate 13-acetate (200 nM) caused an increase in the frequency of miniature
      endplate potentials and miniature endplate currents and in the quantal content of
      endplate potentials and endplate currents. These effects were not replicated by 4
      alpha-phorbol 12,13-didecanoate (200 nM). Nimodipine (1 microM) itself had no
      effect on the frequency of miniature endplate potentials and miniature endplate
      currents and it had no effect on the quantal content. Nimodipine inhibited by 83
      98% the increase in these parameters induced by 4-beta-phorbol 12-myristate 13
      acetate. The increase in the frequency of miniature endplate potentials and
      currents caused by KCl (12 mM) matched the increase caused by 20 min exposure to
      4-beta-phorbol 12-myristate 13-acetate. Nimodipine did not reduce the increase in
      frequency caused by KCl. Unlike 4-beta-phorbol 12-myristate 13-acetate, KCl (12
      mM) prevented neuromuscular transmission. The effects of prior exposure of
      muscles to staurosporine (5 microM) on 4-beta-phorbol 12-myristate 13-acetate
      induced increases in quantal acetylcholine release were inconsistent. In some
      pretreated fibres, 4-beta-phorbol 12-myristate 13-acetate caused increases in
      miniature endplate potential frequency and quantal content which were as great as
      the largest values encountered in fibres that had not been pretreated. In others,
      4-beta-phorbol 12-myristate 13-acetate did not have a marked effect; the
      frequency of the spontaneous potentials and the quantal content of endplate
      potentials recorded in the presence of 4-beta-phorbol 12-myristate 13-acetate
      were sometimes less than their respective control values. Pretreatment with
      calphostin C (500 nM) was more consistent; it prevented by 93-100% the 4-beta
      phorbol 12-myristate 13-acetate-induced increases in the frequency of miniature
      endplate potentials and quantal content.Overall, from these results we suggest
      that activation of protein kinase C increases quantal acetylcholine release by
      opening quiescent L-type Ca(2+) channels in motor nerve terminals at resting
      potential and apparently not by depolarisation.

PMID- 11457599
TI  - Nitric oxide modulates evoked catecholamine release from canine adrenal medulla.
AB  - Nitric oxide has various actions, acting in a neurotransmitter-like role and also
      as a paracrine messenger between vascular endothelial and smooth muscle cells.
      This study was done to determine whether endogenous nitric oxide has a role in
      modulating evoked catecholamine release from the canine adrenal medulla. Isolated
      adrenal glands were perfused with Krebs-Ringer solution as a control, or with
      Krebs-Ringer solution containing either N(G)-monomethyl-L-arginine (L-NMMA; 3x10(
      4) M) to non-selectively inhibit nitric oxide synthase or 7-nitroindazole (10(-4)
      M), a relatively selective inhibitor of neuronal nitric oxide synthase.
      Catecholamine release was evoked using the nicotinic cholinergic agonist 1,1
      dimethyl-4-phenylpiperazinium iodine. From the collected perfusate epinephrine,
      norepinephrine, and dopamine were measured by high performance liquid
      chromatography. Previous studies have shown that in the presence of L-NMMA, basal
      releases of epinephrine, norepinephrine and dopamine are increased. 7
      Nitroindazole had no effect on basal catecholamine release, suggesting that
      nitric oxide from an endothelial source was responsible for the inhibition of
      basal catecholamine release from the adrenal medulla. Epinephrine and
      norepinephrine releases were augmented when either of the nitric oxide synthase
      inhibitors was added during submaximal nicotinic stimulation, indicating that
      endogenous nitric oxide inhibited release of epinephrine and norepinephrine. Both
      neuronal and endothelial nitric oxide synthases appeared to be responsible for
      this inhibition. In summary, these studies suggest that nitric oxide, from both
      neuronal and endothelial sources, modulates evoked catecholamine release from
      canine adrenal medulla, while nitric oxide from an endothelial source is most
      likely responsible for modulation of catecholamine release under basal
      conditions.

PMID- 11457600
TI  - Acute actions of tumor necrosis factor-alpha on intracellular Ca(2+) and K(+)
      currents in human microglia.
AB  - The effects of acute application of the pro-inflammatory cytokine tumor necrosis
      factor-alpha (TNFalpha) on levels of intracellular Ca(2+) ([Ca(2+)]i) and on
      whole-cell outward and inward K(+) currents were studied in cultured human
      microglia. TNFalpha elicited a linear increase in [Ca(2+)]i to a plateau level in
      microglia bathed in either standard physiological saline solution or Ca(2+)-free
      physiological saline solution. The rate of increase of [Ca(2+)]i or the level of
      [Ca(2+)]i attained was not significantly altered in the absence of external
      Ca(2+) indicating that Ca(2+) influx did not contribute appreciably to the
      cytokine-induced rise in [Ca(2+)]i. This point was directly confirmed using
      Mn(2+) quenching where no change in signal fluorescence was observed with
      TNFalpha treatment of microglia in Ca(2+)-free physiological saline solution. The
      rate of increase of [Ca(2+)]i induced by TNFalpha in Ca(2+)-free physiological
      saline solution was not altered by prior application of ATP to deplete inositol
      triphosphate stores indicating that these stores did not contribute to the
      cytokine response. In whole-cell patch clamp recordings, the acute treatment of
      human microglia with TNFalpha led to the expression of an outward K(+) current in
      one-third (14 of 41) of cells. This current was activated at potentials positive
      to -30 mV, showed rapid kinetics of activation with no evident inactivation and
      had an I-V relation exhibiting outward rectification. Analysis of tail currents
      showed reversal of the outward K(+) current near -70 mV and tetraethylammonium
      (10 mM) inhibited the outward K(+) current to 24% of control level. Acute
      application of TNFalpha had no effect to alter inward rectifier currents
      generated from voltage ramps. The signaling pathways involving TNFalpha
      modulation of [Ca(2+)]i and K(+) channels in human microglia may contribute to
      functional and pathological actions of the cytokine in the brain.

PMID- 11457602
TI  - A brief history of forensic entomology.
AB  - Apart from an early case report from China (13th century) and later artistic
      contributions, the first observations on insects and other arthropods as forensic
      indicators were documented in Germany and France during mass exhumations in the
      late 1880s by Reinhard and Hofmann, whom we propose recognizing as co-founders of
      the discipline. After the French publication of Megnin's popular book on the
      applied aspects of forensic entomology, the concept quickly spread to Canada and
      the US. At the time, researchers recognized that the lack of systematic
      observations of forensically important insects stood in the way of their use as
      indicators of postmortem interval. General advances in insect taxonomy, and
      ecology helped close this gap over the following decades. Many early case reports
      dealt with alleged child homicides, including the suspected use of sulphuric
      acid. In this context, it was shown that ants, cockroaches, and freshwater
      arthropods could produce postmortem artifacts suggestive of child abuse. After
      the World Wars, few forensic entomology cases entered the scientific literature.
      From the 1960s to the 1980s, Leclecq and Nuorteva were primarily responsible for
      maintaining the method in Central Europe, with a focus on case work. Since then,
      basic research in the US, Russia and Canada has opened the way to the routine use
      of entomology in forensic investigations. The following article gives a brief
      overview of historic developments in the field. A major focus is on the work done
      between 1850 and 1950. Since sources from that time remain difficult to track
      down, the article also includes a historic bibliographical overview on forensic
      entomology of that era.

PMID- 11457603
TI  - Use of beetles in forensic entomology.
AB  - Beetles (Coleoptera) have been recognised as providing significant entomological
      evidence in the medico-legal field, particularly with reference to dry human
      skeletal remains in the later stages of decomposition. The Dermestidae (skin
      beetles) and Cleridae (bone beetles) have been found as the most common types
      infesting exposed human remains and providing evidence in estimating the minimum
      postmortem interval (PMI).

PMID- 11457604
TI  - Factors affecting decomposition and Diptera colonization.
AB  - Understanding the process of corpse decomposition is basic to establishing the
      postmortem interval (PMI) in any death investigation even using insect evidence.
      The sequence of postmortem changes in soft tissues usually gives an idea of how
      long an individual has been dead. However, modification of the decomposition
      process can considerably alter the estimate of the time of death. A body after
      death is sometimes subject to depredation by various types of animals among which
      insects can have a predominant role in the breakdown of the corpse thus,
      accelerating the decomposition rate. The interference of the insect community in
      the decomposition process has been investigated by several experimental studies
      using animal models and very few contributions directly on cadavers. Several of
      the most frequent factors affecting PMI estimates such as temperature, burial
      depth and access of the body to insects are fully reviewed. On account of their
      activity and world wide distribution, Diptera are the insects of greatest
      forensic interest. The knowledge of factors inhibiting or favouring colonization
      and Diptera development is a necessary pre-requisite for estimating the PMI using
      entomological data.

PMID- 11457605
TI  - Postmortem interval (PMI) determined by study sarcophagous biocenoses: three
      cases from the province of Venice (Italy).
AB  - This paper presents and discusses three cases of cadavers found, unburied, in the
      province of Venice, Northern Italy. In each case, all insect species playing some
      role in carrion decay processes, both sarcophagous and their predators, found on
      or in the bodies, were collected and determined. In one case, many larvae of the
      black soldier fly, Hermetia illucens L. (Diptera: Stratiomyidae) were found and
      are reported, for the first time in Italy, as necrophagous. Experimental breeding
      of some fly species was also carried out in controlled temperature and humidity
      conditions. In particular, it was of interest to know how the Neotropical black
      soldier fly modified its life-cycle to adapt to a temperate climate. It was thus
      possible to establish the rate of larval growth and timing of pupation,
      emergence, oviposition and hatching in various external conditions. The
      postmortem interval (PMI) established by identifying the life-cycle stages of
      dipterofauna were later confirmed in all cases through police investigations and
      the results of forensic analyses.

PMID- 11457606
TI  - Effect of temperature on Lucilia sericata (Diptera: Calliphoridae) development
      with special reference to the isomegalen- and isomorphen-diagram.
AB  - Developmental behavior of eggs, larva and pupa of the blowfly species Lucilia
      sericata (Meigen) were studied under 10 different temperature regimes. Data from
      these studies were used to construct the isomegalen-diagram. In this diagram,
      time from hatching to peakfeeding is plotted against temperature, each line
      representing identical larval length at various temperatures. If the temperature
      is roughly constant, as is the case with corpses found indoors, the age of the
      maggot can be read off instantly from its length, provided that the maggot has
      not entered the migratory phase. Where temperature is variable, an age range can
      be estimated between the points where the measured larval length cuts the graph
      at the maximum and minimum temperatures recorded. Equally, the isomorphen-diagram
      representing all morphological stages from oviposition to eclosion should be
      used, if maggots in the migratory phase or pupae or puparia are recovered from
      the scene. The isomegalen- and the isomorphen-diagrams could facilitate a quick
      and more precise estimate of the postmortem interval even for the inexperienced
      investigator. In addition, our results vary from those of other investigators,
      suggesting a different thermal behavior of the holarctic blowfly L. sericata in
      various zoogeographic regions.

PMID- 11457607
TI  - Preliminary observations on the effects of hydrocortisone and sodium methohexital
      on development of Sarcophaga (Curranea) tibialis Macquart (Diptera:
      Sarcophagidae), and implications for estimating post mortem interval.
AB  - Larvae of Sarcophaga (Curranea) tibialis (S. tibialis) were reared at constant
      temperature on chicken liver treated with a steroid or a barbiturate at
      concentrations that would be lethal, half-lethal and twice-lethal doses for
      humans. Trends to greater mortality at higher drug concentrations were not
      statistically significant. Larvae exposed to either drug took significantly
      longer to reach pupation compared to those in the control, while larvae exposed
      to sodium methohexital passed through pupation significantly faster than those in
      the control. No systematic relationship was found between drug concentration and
      development time of larvae or pupae. The total developmental period from hatching
      to eclosion did not differ between treatments, implying that estimates of post
      mortem intervals- (PMI) based on the emergence of adult flies will not be
      affected by the involvement of these drugs in a case. On the other hand,
      anomalous pupation spans may indicate the presence of barbiturates. These
      findings are compared with patterns found in another fly fed other contaminants.

PMID- 11457608
TI  - Entomotoxicology.
AB  - Entomotoxicology is a relatively new branch of forensic entomology. The potential
      use of insects for detecting drugs and other toxins in decomposing tissues has
      been widely demonstrated. In death investigations, Diptera and other arthropods
      can be reliable alternate specimens for toxicological analyses in the absence of
      tissues and fluids normally taken for such purposes. Entomotoxicology also
      investigates the effects caused by drugs and toxins on arthropod development in
      order to assist the forensic postmortem interval estimates. However, several
      remarks on the limitations of entomotoxicology have been highlighted recently. In
      this paper, the implications for the practice of this forensic procedure are
      fully reviewed.

PMID- 11457609
TI  - Forensic entomology: application, education and research in Western Australia.
AB  - Forensic entomology as a science and a tool for investigation has had slow
      beginnings in Australia. A number of small animal decomposition trials have been
      recorded in the literature but mostly from an ecological rather than a forensic
      entomology perspective. In the last 20 years, a number of more forensically
      orientated field trials on small pigs and some fly developmental trials in the
      laboratory have been conducted but lack any replication. The following article
      was presented at an international seminar to detail the current research in
      forensic entomology, the applications of forensic entomology in scene of crime
      (SOC) and homicide investigations and the education of police and judiciary in
      the discipline of forensic entomology in Western Australia over the last 10
      years.

PMID- 11457610
TI  - A preliminary study of forensic entomology in Medellin, Colombia.
AB  - This is the first report of an ongoing study of insect succession on carrion
      carried out in Medellin, Colombia, using pigs (Sus scrofa) as a model to
      determine the insect sequence over 207 days. During this period, 2314 insects
      belonging to the following orders and families were collected: Diptera:
      Calliphoridae, Muscidae, Piophilidae, Sarcophagidae, Syrphidae, Otitidae;
      Hymenoptera: Apidae, Formicidae, Halictidae, Mutilidae, Vespidae; Coleoptera:
      Staphylinidae, Histeridae, Carabidae, Scarabaeidae, Silphidae, Dermestidae,
      Cleridae, Nitidulidae; Dermaptera: Forficulidae; Hemyptera: Gelastocoridae,
      Coreidae; Lepidoptera: Hesperiidae. Five decomposition stages were observed
      (fresh, bloated, active decay, advanced decay, and dry remains) and four insect
      ecological categories (necrophagous, predators, omnivorous, and incidental).
      During the fresh stage, the first insects that appeared were flies of the
      families Sarcophagidae and Muscidae and specimens of Formicidae (Hymenoptera).
      During the bloated period, species of Calliphoridae (Diptera) were predominant
      and the first to oviposit. During the third and fourth stages (active decay and
      advanced decay), the most abundant families were Calliphoridae and Muscidae,
      although Staphilinidae (Coleoptera) also stood out. During the last stage (dry
      remains), the dominant family was Formicidae (Hymenoptera) followed by
      Dermestidae (Coleoptera) with a large number of immature insects.

PMID- 11457611
TI  - The utility of mitochondrial DNA sequences for the identification of forensically
      important blowflies (Diptera: Calliphoridae) in southeastern Australia.
AB  - The applicability of mitochondrial DNA (mtDNA) sequencing was investigated for
      the identification of the following forensically important species of blowflies
      from southeastern Australia: Calliphora albifrontalis, C. augur, C. dubia, C.
      hilli hilli, C. maritima, C. stygia, C. vicina, Chrysomya rufifacies, Ch. varipes
      and Onesia tibialis. All breed in carrion except O. tibialis, which is an
      earthworm parasitoid. Emphasis was placed on Calliphora species because they
      predominate among the carrion-breeding blowfly fauna of southern Australia and
      their immatures are difficult to identify morphologically. A partial sequence of
      the mitochondrial COII gene was determined for all species and for COI for C.
      albifrontalis, C. augur, C. dubia and C. stygia only. Five other species of
      blowflies, Chrysomya albiceps, Ch. rufifacies, Protophormia terraenovae, Lucilia
      illustris and L. sericata, for which sequence data were already available, were
      also included. Analysis of the COI and COII sequences revealed abundant
      phylogenetically informative nucleotide substitutions that could identify blowfly
      species to species group. In contrast, because of the low level of sequence
      divergence of sister species, the data could not distinguish among taxa from the
      same species group, i.e. the species within the C. augur and C. stygia groups.
      The molecular data support the existing species group separation of the taxa
      within Calliphora. Because of the speed and accuracy of current nucleotide
      sequencing technology and the abundant apomorphic substitutions available from
      mtDNA sequences, this approach, with the analysis of additional taxa and genes,
      is likely to enable the reliable identification of carrion-breeding blowflies in
      Australia.

PMID- 11457612
TI  - Activity of the forensic entomology department of the French Gendarmerie.
AB  - The criminal research Institute of the French Gendarmerie deals with several
      disciplines which are part of forensic science. Forensic entomology is one of the
      last laboratories created in Rosny-Sous-Bois. As with all other departments of
      the Institute, its main mission is carrying out its expertise on behalf of
      justice. Another important mission is to educate on one hand the "scene of crime"
      officers in order to increase the quality of the specimens collected and on the
      other hand to magistrates to make forensic entomology better known. At last, a
      research program is available to follow scientific development and to improve
      services to justice.

PMID- 11457613
TI  - Stability of prostate specific antigen (PSA), and subsequent Y-STR typing, of
      Lucilia (Phaenicia) sericata (Meigen) (Diptera: Calliphoridae) maggots reared
      from a simulated postmortem sexual assault.
AB  - Rape-homicide represents one of the most heinous crimes, but which are also the
      hardest to solve due to the high occurrence of stranger-to-stranger interaction.
      This is the first case of obtaining P30 and Y-STR typing from a simulated
      postmortem sexual assault. 2, 3.5 and 6 microl of liquid semen was added to a
      liver substrate and Lucilia (Phaenicia) sericata (Meigen) eggs added. The larvae
      fed upon the semen coated substrate and were removed for testing after 48 and
      145h after initial liquid semen deposition. P30 was recorded from whole
      postfeeding larvae after 145h, with correct Y-STR profiles obtained from the crop
      of actively feeding second instar larvae after 48h of initial semen deposition.
      The ability to obtain P30 and Y-STR profiles from larvae infesting a cadaver,
      with the suspicion of sexual assault having occurred prior to death, provides a
      new avenue to aid in the solving of such crimes.

PMID- 11457614
TI  - Dead larvae of Cynomya mortuorum (L.) (Diptera, Calliphoridae) as indicators of
      the post-mortem interval--a case history from Norway.
AB  - A case history where the presence of dead third instar larvae of Cynomya
      mortuorum (L.) provided information regarding the post-mortem interval is
      reported. Some (15-20) dead larvae were located in the mouth of the deceased, and
      data on the seasonal distribution of this species placed the time of death some 7
      months prior to the discovery in May 1996, i.e. to October 1995. In this case,
      the entomological data matched the information later provided by the police.

PMID- 11457615
TI  - The development of the black blow fly, Phormia regina (Meigen).
AB  - The black blow fly, Phormia regina (Meigen) is a primary species commonly
      utilized to indicate a postmortem interval, or more appropriately a "time since
      colonization". Due to the importance of this species as a secondary myiasis
      producer in livestock operations, and more recently as a time since death
      indicator in the field of forensic entomology, a considerable amount of data on
      its growth and development has been generated. However, the developmental time as
      reported by these studies varies greatly, and current more detailed data is
      needed for use in medicocriminal entomology. Hourly developmental data is
      presented under constant temperatures of 10, 15, 20, 25, 30, 35 and 40 degrees C,
      and cyclic temperatures of 10-15, 15-25, 25-35 and 35-45 degrees C. This study is
      in agreement with the results reported by Kamal [Comparative study of thirteen
      species of sarcosaprophagous Calliphoridae and Sarcophagidae (Diptera). I.
      Bionomics, Ann. Entomol. Soc. Am. 51 (1958) 261] and Melvin [Incubation period of
      eggs of certain musciod flies at different constant temperatures, Ann. Entomol.
      Soc. Am. 27 (1934) 406] only at temperatures of 25 degrees C and below. Bishopp
      [Flies which cause myiasis in man and animals: some aspects of the problem, J.
      Econ. Entomol. 8 (1915) 317] reported a shorter developmental duration for larval
      stages than what was produced with our laboratory rearings.

PMID- 11457616
TI  - Medicolegal relevance of cadaver entomofauna for the determination of the time of
      death.

PMID- 11457617
TI  - DNA-based identification of forensically important Chrysomyinae (Diptera:
      Calliphoridae).
AB  - Identifying an insect specimen is an important first step in a forensic
      entomological analysis. However, diagnostic morphological criteria are lacking
      for many species and life stages. We demonstrate a method for using mitochondrial
      DNA sequence data and phylogenetic analysis to identify any specimen of the blow
      fly subfamily Chrysomyinae likely to be collected from a human corpse within
      Canada or the USA. The reliability of the method was illustrated by analyzing
      specimens designed to mimic the information likely to be obtained from highly
      degraded specimens as well as specimens collected from widely separated
      geographic locations. Our sequence database may be suitable for another country
      provided the investigator knows the local fly fauna well enough to narrow the
      choice of chrysomyine species to those used in this study.

PMID- 11457618
TI  - Genetic relationships between blowflies (Calliphoridae) of forensic importance.
AB  - Phylogenetic relationships among blowfly (Calliphoridae) species of forensic
      importance are explored using DNA sequence data from the large sub-unit (lsu,
      28S) ribosomal RNA (rRNA) gene, the study includes representatives of a range of
      calliphorid species commonly encountered in forensic analysis in Britain and
      Europe. The data presented provide a basis to define molecular markers, including
      the identification of highly informative intra-sequence regions, which may be of
      use in the identification of larvae for forensic entomology. Phylogenetic
      analysis of the sequences also provides new insights into the different
      evolutionary patterns apparent within the family Calliphoridae which,
      additionally, can provide a measure of the degree of genetic variation likely to
      be encountered within taxonomic groups of differing forensic utility.

PMID- 11457619
TI  - Further observations on the nocturnal oviposition behaviour of blow flies
      (Diptera: Calliphoridae).
AB  - Calculating the age of immature stages of blow flies showing the longest period
      of association with a dead body often gives a fairly accurate estimate of the
      post-mortem interval (PMI). Determination of the exact time of oviposition by
      these flies had generally been made in the light of the conventional belief that
      blow flies are neither active nor do they lay eggs during night. This method of
      estimating the time of oviposition was modified when Greenberg [J. Med. Entomol.
      27 (1990) 807] reported nocturnal oviposition by three calliphorid species that
      are occasionally used as forensic indicators. However, a technical problem with
      his experiment, having long term consequences, was placement of the bait on the
      ground among bushes. This could have made it possible for the flies already
      resting near the bait to climb over the piece of meat and lay eggs. Though
      Greenberg's experiment proves beyond any doubt that blow flies do lay eggs at
      night as well as by day, active attraction of these flies at night towards the
      oviposition medium had yet to be proved and the present experiment has been
      designed for this purpose.

PMID- 11457620
TI  - Morphine extraction in necrophagous insects remains for determining ante-mortem
      opiate intoxication.
AB  - To study the potential use of insects remains as toxicological indicators, we
      measured morphine in desiccated entomological materials using a radioimmunoassay
      method (Coat-A-Count Serum Morphine, Dade Behring, France) following enzymatic
      hydrolysis.First, enzymatic cuticle extraction of morphine (pronase digestion
      preceded by a 2h incubation with a dithiothreitol solution) was performed on
      various substrates (Calliphoridae puparial cases and desiccated adults, and
      desiccated pupae of Dermestidae) which were then tested to identify possible
      interferences with the radioimmunoassay procedure. This same procedure was
      performed on puparial cases and desiccated adults of Lucilia sericata (Diptera,
      Calliphoridae) previously reared on minced meat containing various morphine
      concentrations. Morphine was detected only in cuticle powder from insects reared
      on meats containing 100 and 1000mg/kg. Higher concentrations were measured in
      puparial cases. Rearings on psoas from eight heroin overdose victims confirmed
      previous experimental results. Remains of necrophagous insects, particularly
      puparial cases, are often preserved for a long time, and consequently can serve
      as late alternative specimens for toxicological analysis when suitable tissues
      are not available.

PMID- 11457621
TI  - The forensic entomologist in the context of the forensic pathologist's role.
AB  - An adequate death investigation requires the combined efforts and cooperation of
      experts in different disciplines: crime scene technicians, death investigators,
      forensic pathologists, anthropologists, entomologists, other medical and non
      medical professionals. These front-line experts play a crucial role in every
      death investigation process. The forensic pathologist normally has the legal
      authority to take charge of the dead body at a death scene and his primary
      functions are the exterior and interior examination of the cadaver by analyzing
      the extent of antemortem injuries and the postmortem changes and the recovery of
      physical evidence. He is responsible for determining how, when and why of any
      death which is the result of violence, suspicious or unexplained circumstances or
      a death which is sudden or unattended, defending and explaining the reasons for
      making these diagnoses in a courtroom. The forensic entomologist can provide
      invaluable aid in death cases where human remains are colonized by insects and in
      the overall investigation. His principal role is to identify the arthropods
      associated with such cases and to analyze entomological data for interpreting
      insect evidence. He is responsible for determining the period of insect activity
      according to all the variables affecting insect invasion of remains and their
      development. The major goal of medico-criminal entomology is to contribute to the
      determination of the time, cause, manner and place of the investigated death
      (especially on badly decomposed corpses or skeletonized human remains) with the
      support of all the elements which can be inferred from the study of insects found
      on the cadaver or nearby. The application of techniques devised recently in
      forensic entomology can allow experts in the field to collect strong
      entomological evidence and provide useful information not only in a death
      investigation including movement or storage of the remains following death, time
      of dismemberment, postmortem artifacts on the body but also at the scene, and
      even more in child neglect, sexual molestation and identification of suspects. As
      the role of the forensic entomologist at the death scene, at the autopsy and in
      the laboratory is defined and well known, this paper focuses on the difficulties
      that could arise if forensic pathologists and entomologists are uncertain about
      the procedures that they have to follow, do not realize the value of objective
      findings or fail to evaluate them. Although every forensic case presents a
      slightly different set of circumstances and has to be tackled individually, the
      forensic pathologist should work with the forensic entomologist from the visual
      observations of the cadaver on the scene, through the collection of arthropods
      and temperature data at the death scene and at the autopsy, up to the final
      report with the interpretation of entomological and other biological evidence.

PMID- 11457622
TI  - Determination of drug levels and the effect of diazepam on the growth of
      necrophagous flies of forensic importance in southeastern Brazil.
AB  - Larvae of Chrysomya albiceps (Wiedemann) and Chrysomya putoria (Wiedemann)
      (Diptera: Calliphoridae) were reared on tissues from rabbits administered twice
      the lethal dosage of diazepam in order to study the effects of this drug on the
      development of these two species. The rabbits were given 50mg of diazepam via ear
      vein infusion. From 18 to 54h, larvae feeding on tissues containing the drug
      developed more rapidly than larvae from the control colony for both fly species.
      The time required for pupariation and adult emergence was significantly greater
      for colony fed on tissues from diazepam dosed rabbits than for the control ones.
      These differences are significant for they are large enough to alter the estimate
      of postmortem interval based on fly development. The presence of diazepam could
      be detected through gas chromatography-mass spectrometer (GC-MS) in all rabbit
      samples and in almost all diptera samples in this experiment.

PMID- 11457623
TI  - Insects of forensic significance in Argentina.
AB  - Records from forensic expertises and trappings with beef baits conducted in
      Buenos Aires, Argentina (34 degrees 36'S), show that the dominating species are
      widespread ones (Calliphora vicina and Phaenicia sericata), with different
      behaviour in each large latitudinal zone. It is suggested that the range of the
      yearly photoperiod variation has an influence in the behaviour of the blowflies,
      making up for differences in the succession patterns. The Calliphorid blowflies
      Cochliomyia macellaria and Chysomya albiceps were found on indoors corpses; the
      latter also on outdoors corpses when blood was shed, and in that case as primary.
      Three species of beetles of the genus Dermestes, which had been associated with
      mummified remains, appeared 10-30 days after death. The Silphid beetle
      Hyponecrodes sp. cf. erythrura was found on outdoor copses in rural environments.
      The Nitidulid beetle Carpophilus hemipterus was found in association with the
      cheese skipper Piophila sp. (Diptera: Piophilidae) in medullar cavities of bones
      after ca. 30 days; to this association is often added the Clerid Necrobia
      rufipes. Lepidoptera Tineidae appear on the head of mummified indoors corpses.
      North of parallel 32 degrees S, the Muscid grave-fly Ophyra sp. was found
      breeding on a corpse outdoors in summer. A division by latitude and climate is
      proposed for Argentina, and an extended system is proposed for the world.

PMID- 11457624
TI  - Child neglect and forensic entomology.
AB  - Close co-operation between forensic scientists, medico-legal doctors, and police
      forces made it possible to estimate not only the post-mortem interval but also
      the time since a child was neglected. On the skin surface under the diaper (anal
      genital area), third instar larvae of the false stable fly Muscina stabulans
      FALLEN, and the lesser house fly Fannia canicularis L. were found. F. canicularis
      adults are attracted to both feces and urine. From the face, larvae of the
      bluebottle fly Calliphora vomitoria L. were collected. C. vomitoria maggots are
      typical early inhabitants of corpses. From the developmental times of the flies,
      it was estimated that the anal-genital area of the child had not been cleaned for
      about 14 days (7-21 day range), and that death occurred only 6-8 days prior to
      discovery of the body. This is the first report where an examination of the
      maggot fauna on a person illustrated neglect that had occurred prior to death.

PMID- 11457625
TI  - Technical note.

PMID- 11457626
TI  - Handwashing and respiratory illness among young adults in military training.
AB  - OBJECTIVES: In response to increasing concerns about respiratory illness in
      military recruits, a simple handwashing program was developed and evaluated at a
      large Navy training center. METHODS: Clinical records from 1996 through 1998 were
      reviewed to determine weekly rates of respiratory illness before and after
      program implementation (1,089,800 person-weeks reviewed). A supplemental survey
      was given to a sample of recruits to assess self-reported respiratory illness and
      compliance with the handwashing program. RESULTS: A 45% reduction in total
      outpatient visits for respiratory illness was observed after implementation of
      the handwashing program. No change was noted in hospitalization rates for
      respiratory illness, which remained low during the observation period. Survey
      data supported clinical observations, as frequent handwashers self-reported fewer
      respiratory illness episodes when compared to infrequent handwashers. Surveys
      also revealed challenges with handwashing compliance. CONCLUSIONS: Implementation
      of a handwashing program in this population of healthy young adults was
      associated with a marked reduction in outpatient visits for respiratory illness.
      Despite its success, maintenance of the handwashing program has been challenging
      in the time-constrained setting of military training.

PMID- 11457627
TI  - Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive
      people.
AB  - BACKGROUND: As many as one in three HIV-positive people continue unprotected
      sexual practices after learning that they are HIV infected. This article reports
      the outcomes of a theory-based intervention to reduce risk of HIV transmission
      for people living with HIV infection. METHODS: Men (n=233) and women (n=99)
      living with HIV-AIDS were randomly assigned to receive either (1) a five-session
      group intervention focused on strategies for practicing safer sexual behavior, or
      (2) a five-session, contact-matched, health-maintenance support group (standard
      of-care comparison). Participants were followed for 6 months post-intervention.
      RESULTS: The intervention to reduce risk of HIV transmission resulted in
      significantly less unprotected intercourse and greater condom use at follow-up.
      Transmission-risk behaviors with non-HIV-positive sexual partners and estimated
      HIV transmission rates over a 1-year horizon were also significantly lower for
      the behavioral risk-reduction intervention group. CONCLUSIONS: This study is
      among the first to demonstrate successful HIV-transmission risk reduction
      resulting from a behavioral intervention tailored for HIV-positive men and women.

PMID- 11457628
TI  - Predictive validity of a screen for partner violence against women.
AB  - BACKGROUND: While public health leaders recommend screening for partner violence,
      the predictive value of this practice is unknown. The purpose of this study was
      to test the ability of a brief three-question violence screen to predict violence
      against women in the ensuing months. METHODS: We conducted a prospective cohort
      study of adult women participating in the Colorado Behavioral Risk Factor
      Surveillance System (BRFSS), a population-based, random-digit-dialing telephone
      survey. During 8 monthly cohorts, 695 women participated in the BRFSS; 409 women
      participated in follow-up telephone interviews approximately 4 months later.
      Violent events during the follow-up period, measured using a modified 28-item
      Conflict Tactics Scale, were compared between women who initially screened
      positive and those who screened negative. RESULTS: Among BRFSS respondents, 8.4%
      (95% confidence interval [CI]=6.3%-10.5%) had an initial positive screen. During
      the follow-up period, women who screened positive were 46.5 times (5.4-405) more
      likely to experience severe physical violence, 11.7 times (5.0- 27.3) more likely
      to experience physical violence, 3.6 (2.4-5.2) times more likely to experience
      verbal aggression, and 2.5 times (1.2-5.1) more likely to experience sexual
      coercion. In a multivariate model, separation from one's spouse and a positive
      screen were significant independent predictors of physical violence. CONCLUSIONS:
      A brief violence screen identifies a subset of women at high risk for verbal,
      physical, and sexual partner abuse over the following 4 months. Women with a
      positive screen who are separated from their spouse are at highest risk.

PMID- 11457629
TI  - Effects of the CATCH physical education intervention: teacher type and lesson
      location.
AB  - BACKGROUND: Substantial differences exist in how and where physical education
      (PE) is conducted in elementary schools throughout the United States. Few
      effectiveness studies of large-scale interventions to improve PE have been
      reported. DESIGN: Multicenter randomized trial. SETTING/ PARTICIPANTS: The Child
      and Adolescent Trial for Cardiovascular Health (CATCH) was implemented in PE
      classes in 96 schools (56 intervention, 40 control) in four study centers:
      California, Louisiana, Minnesota, and Texas. INTERVENTION: The 2.5-year PE
      intervention consisted of professional development sessions, curricula, and
      follow-up consultations. MAIN OUTCOME MEASURES: Intervention effects on student
      physical activity and lesson context in PE were examined by teacher type (PE
      specialists and classroom teachers) and lesson location (indoors and outdoors).
      RESULTS: Differential effects by teacher type and lesson location were evidenced
      for both physical activity and lesson context. Observations of 2016 lessons
      showed that intervention schools provided more moderate-to-vigorous physical
      activity (p=0.002) and vigorous physical activity (p=0.02) than controls.
      Classroom teachers improved physical activity relatively more than PE
      specialists, but PE specialists still provided longer lessons and more physical
      activity. Classroom teachers increased lesson length (p=0.02) and time for
      physical fitness (p=0.03). CONCLUSIONS: The intervention improved PE of both
      specialists' and classroom teachers' lessons. States and districts should ensure
      that the most qualified staff teaches PE. Interventions need to be tailored to
      meet local needs and conditions, including teacher type and location of lessons.

PMID- 11457630
TI  - Measuring enjoyment of physical activity in adolescent girls.
AB  - BACKGROUND: Enjoyment has been implicated as a determinant of physical activity
      among youth, but advances in understanding its importance have been limited by
      the use of measures that were not adequately validated. The present study
      examined: (1) the factorial validity of the Physical Activity Enjoyment Scale
      (PACES), and (2) the construct validity of PACES scores. METHODS: Adolescent
      girls (N=1797), who were randomly assigned to calibration (n=899) and cross
      validation (n=898) samples, completed the PACES and measures of factors
      influencing enjoyment of physical education, physical activity, and sport
      involvement. The factorial validity of the PACES and the measure of factors
      influencing enjoyment of physical education was tested using exploratory and
      confirmatory factor analysis. The hypothesized relationships among the measures
      were tested using structural equation modeling. RESULTS: Unidimensional models
      fit the PACES and the measure of factors influencing enjoyment of physical
      education in the calibration and cross-validation samples. The hypothesized
      relationships between the PACES and the measures of factors influencing enjoyment
      of physical education, physical activity, and sport involvement were supported in
      the entire sample, were similar in African-American and Caucasian girls, and were
      independent of physical fitness. CONCLUSIONS: Evidence of factorial validity and
      convergent evidence for construct validity indicate that the PACES is a valid
      measure of physical activity enjoyment among adolescent girls, suitable for use
      as a mediator variable in interventions designed to increase physical activity.

PMID- 11457631
TI  - Firearm storage practices of officers in a law enforcement agency in the South.
AB  - BACKGROUND: Law enforcement officers play an important role in promoting firearm
      safety. This study examined their firearm-related attitudes and practices.
      METHODS: We conducted an anonymous, self-administered survey of law enforcement
      officers in an agency in the South concerning firearm ownership, storage
      practices, and opinions. RESULTS: The 207 respondents (response rate=71%) were
      primarily white (60%) and male (89%). The proportions of respondents with (55%)
      and without (45%) children were similar. Eighty percent of the officers had
      firearms in addition to the one they were issued for work. Most stored firearms
      unlocked (59%) and loaded (68%); almost half (44%) reported storing firearms both
      unlocked and loaded. Eighty-five percent indicated that they felt an added need
      to protect themselves and family because of their job. Those who reported having
      firearms for self-protection were less likely than those who had firearms for
      recreation to store firearms securely. As compared to those without children, law
      enforcement officers with children were more likely to store firearms safely, and
      were especially likely to store firearms locked up (chi(2)=12.72, p<0.0001).
      Respondents favored background checks, mandatory safety training, and enforcement
      of storage laws. Three quarters approved of government safety regulations for
      handguns. CONCLUSIONS: Despite the law enforcement officers' prominent role in
      firearm safety promotion and support for initiatives that limit unauthorized
      access, our study found that many do not practice safe storage. Apparently, many
      officers keep their firearms stored unlocked and loaded for the purpose of
      protecting themselves and their families. Addressing concerns about personal
      safety is a necessary step in promoting safe storage to law enforcement officers.

PMID- 11457632
TI  - Quality of diabetes care among low-income patients in North Carolina.
AB  - BACKGROUND: Diabetes is a leading cause of death and disability,
      disproportionately affecting most ethnic minority groups, people of low
      socioeconomic status, the elderly, and people in rural areas. Despite the
      availability of evidence-based clinical recommendations, barriers exist in the
      delivery of appropriate diabetes care. The purpose of this study is to examine
      the level of diabetes care among low-income populations in North Carolina.
      METHODS: Baseline medical record abstractions were performed (N=429) on diabetic
      patients at 11 agencies serving low-income populations (community health centers,
      free clinics, primary care clinics, and public health clinics) across the state
      participating in a quality-of-diabetes-care initiative. Data were collected for
      four process (measurement of glycosylated hemoglobin and lipids, dilated eye
      examination, nephropathy assessment) and two outcome (glycemic and lipid control)
      measures based on the Diabetes Quality Improvement Project (DQIP) and the Health
      Plan Employer Data and Information Set (HEDIS), and three additional indicators
      (blood pressure measurement and control, and lower limb assessment). Compliance
      rates to individual measures were calculated overall and by demographic and
      health characteristics. RESULTS: Diabetes care compliance rates ranged from 77.9%
      for blood pressure testing to 3.3% for complete foot examinations. Differences in
      care were observed by age, insulin use, and prevalent disease. CONCLUSIONS: This
      study indicates low compliance with diabetes care guidelines in underserved North
      Carolinians, and inconsistency of care according to some demographic and health
      characteristics. These results stress the need for quality improvement
      initiatives that enhance the level of care received by patients with diabetes,
      particularly those most vulnerable to diabetes and its complications.

PMID- 11457633
TI  - Colorectal cancer-screening tests and associated health behaviors.
AB  - BACKGROUND: Studies have shown that screening reduces colorectal cancer
      mortality. We analyzed national survey data to determine rates of use of fecal
      occult blood testing (FOBT) and sigmoidoscopy, and to determine if these rates
      differ by demographic factors and other health behaviors. METHODS: A total of
      52,754 respondents aged >or=50 years were questioned in the 1997 Behavioral Risk
      Factor Surveillance System (BRFSS) survey (a random-digit-dialing telephone
      survey of the non-institutionalized U.S. population) about their use of FOBT and
      sigmoidoscopy. RESULTS: The age-adjusted proportion of respondents who reported
      having had a colorectal cancer screening test during the recommended time
      interval (past year for FOBT and past 5 years for sigmoidoscopy) was 19.8% for
      FOBT, 30.5% for sigmoidoscopy, and 41.1% for either FOBT or sigmoidoscopy. Rates
      of use of colorectal cancer screening tests were higher for those who had other
      screening tests (mammography, Papanicolaou smear, and cholesterol check). There
      were also differences in rates of use of colorectal cancer screening tests
      according to other health behaviors (smoking, seat belt use, fruit and vegetable
      intake, and physical activity) and several demographic factors. However, none of
      the subgroups that we examined reported a rate of FOBT use above 29% within the
      past year or a rate of sigmoidoscopy use above 41% within the past 5 years.
      CONCLUSIONS: While rates of use of FOBT and sigmoidoscopy were higher among
      people who practiced other healthy behaviors, rates of use were still quite low
      in all subgroups. There is a need for increased awareness of the importance of
      colorectal cancer screening.

PMID- 11457634
TI  - Acceptability of the Checkpoints Parent-Teen Driving Agreement: pilot test.
AB  - BACKGROUND: Parent-teen driving agreements are potentially important tools to
      facilitate parental management of teen driving and reduce adolescent driving
      risk. The Checkpoints Parent-Teen Driving Agreement (Checkpoints P-TDA) was
      designed so that parents could initially impose strict limitations on teen
      driving in high-risk driving conditions (e.g., at night and with teen passengers)
      and gradually increase driving privileges over time as teens demonstrate
      responsible driving behavior. METHODS: To assess the acceptability of the format
      and content of the Checkpoints P-TDA, it was pilot tested with a convenience
      sample of 47 families recruited as their teens tested for a driver's license at
      five private driving schools in Connecticut. Family members were interviewed at
      the driving schools about potential limits on teen driving, asked to use the
      driving agreement, and re-interviewed within 3 months about acceptability of the
      driving agreement and initial driving limits placed on teens. RESULTS: Most
      families (38 of 47) used and liked the agreement. In addition, most parents
      placed the recommended strict initial limits on teen driving related to driving
      unsupervised at night, with teen passengers, and on high-speed roads. Moreover,
      parents reported placing more strict limits on their teens' driving than they
      originally intended. CONCLUSIONS: The results showed promise for the
      acceptability of the Checkpoints P-TDA, which will be tested statewide.

PMID- 11457635
TI  - Smoking among lesbians, gays, and bisexuals: a review of the literature.
AB  - OBJECTIVES: To collect estimates of smoking prevalence among lesbian, gay, and
      bisexual people from the published literature and to compare with general
      population estimates. METHODS: Databases were searched for all studies published
      in English on tobacco use among lesbians, gays, and bisexuals. From 1987 through
      2000, twelve studies were identified (four youth, eight adult): seven were based
      on convenience samples; one on a population-based probability sample; one
      involved random sampling within selected census tracts; one was based on a large
      multicenter clinical trial; and two were representative school-based samples.
      Study findings were compared to national survey data from the corresponding time
      period. RESULTS: Estimated smoking rates for lesbians, gays, and bisexuals ranged
      from 38% to 59% among youth and from 11% to 50% among adults. National smoking
      rates during comparable periods ranged from 28% to 35% for adolescents and were
      approximately 28% for adults. CONCLUSIONS: While information in the published
      literature is limited, it appears that smoking rates are higher among adolescent
      and adult lesbians, gays, and bisexuals than in the general population. Steps
      should be taken to ensure representation of lesbians, gays, and bisexuals in
      tobacco-use surveillance and to collect data in order to understand the apparent
      high smoking rates in these groups. Attempts should be made to target prevention
      and cessation interventions to lesbians, gays, and bisexuals.

PMID- 11457636
TI  - Returning to the past: respiratory illness, vaccines, and handwashing.

PMID- 11457637
TI  - Growth inhibition of primary keratinocytes following transduction with a novel
      TGFbeta-1 containing retrovirus.
AB  - Growth and migration of keratinocytes are known to be affected by the addition of
      exogenous cytokines, such as TGFbeta-1, to culture media. We have developed a
      retroviral vector, LNTbeta-1, that confers constitutive expression of human
      TGFbeta-1 to transduced cells. Keratinocytes were exposed to retroviral particles
      generated in serum-free media, and infected cells were selected for with
      Geneticin. Transduced keratinocytes remained in culture as single cells instead
      of a normally grouped growth pattern. While these transduced keratinocytes
      survived in culture for several weeks, they did not proliferate and seemed
      arrested in their growth. Keratinocytes transduced with retrovirus not containing
      the TGFbeta-1 gene appeared normal in their growth pattern. These findings
      indicate that high-level endogenous expression of TGFbeta-1 in keratinocytes can
      at least inhibit, and possibly arrest, growth.

PMID- 11457638
TI  - Topical application of cyclosporin A induces rapid-remodeling of damaged anagen
      hair follicles produced in cyclophosphamide administered mice.
AB  - Adult C3H mice which had either anagen IV or anagen VI hair follicles were given
      the anti-tumor drug cyclophosphamide, and cyclosporin A or minoxidil were
      topically applied to the mice daily from the 4th day after cyclophosphamide
      administration. In the mice that had anagen IV-hair follicles, 0.5% cyclosporin A
      induced very thick and long hairs after 21 days of cyclophosphamide
      administration, while vehicle and 1% minoxidil induced sparsely visible, short
      hairs. In the mice which received cyclosporin A, the injured hair follicles
      seemed to remodel themselves into intact anagen hair follicles and restart the
      production of hairs, instead of shifting to telogen. In the mice that had anagen
      VI-hair follicles at the time of cyclophosphamide administration, complete
      alopecia occurred within the first 7 days in all groups. After 14 days of
      cyclophosphamide administration, hair regrowth was observed in both the 0.5%
      cyclosporin A-group and the 1% minoxidil- group with the predominant effect over
      the vehicle. This study shows that anagen hair follicles respond to
      cyclophosphamide in different ways depending on their stages (IV and VI), and
      that the damaged anagen IV hair follicles have the potential of remodeling
      themselves, which is promoted by topical cyclosporin A administration.

PMID- 11457639
TI  - Molecular epidemiology of Arthroderma benhamiae, an emerging pathogen of
      dermatophytoses in Japan, by polymorphisms of the non-transcribed spacer region
      of the ribosomal DNA.
AB  - In Japan, several isolates of Arthroderma benhamiae, a teleomorphic member of
      Trichophyton mentagrophytes complex, which were not found by earlier mating
      studies, have recently been recovered from human and animal dermatophytoses. In
      the present study, intraspecies polymorphism of A. benhamiae isolated in Japan
      was investigated using restriction fragment length polymorphisms (RFLP) of the
      non-transcribed spacer (NTS) region of the ribosomal DNA (rDNA), a method
      introduced to detect intraspecies polymorphisms of other dermatophyte species,
      such as T. rubrum. Based on their restriction profiles, there were five DNA types
      out of eight strains of A. benhamiae isolated in Japan. None of the five DNA
      types were found among the registered tester strains of A. benhamiae. Therefore,
      several different strains of A. benhamiae may have been brought into Japan
      separately.

PMID- 11457640
TI  - Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell
      carcinoma syndrome.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder
      characterized by developmental and skeletal anomalies, palmo-plantar pits,
      odontogenic keratocysts, ectopic calcification, and occurrence of various types
      of tumors including basal cell carcinoma. Recent evidence has indicated that the
      human homologue of a Drosophila segment polarity gene, PTCH, is a NBCCS
      susceptibility gene. In the study presented here, we detected two novel mutations
      of the PTCH gene, I805X/2395delC and Y93X/C297A, in two unrelated Japanese
      patients. Early protection of the skin from the sunlight is important to the
      prevention of BCC development in NBCCS patients. Genetic analysis of the PTCH
      gene is essential for the early, definitive diagnosis of NBCCS, especially before
      the expression of clinical manifestations is complete.

PMID- 11457641
TI  - Erythrocyte membrane fluidity changes in psoriasis: an EPR study.
AB  - The aim of the study was to find the cause of membrane fluidity decrease in
      psoriasis, observed by other authors, in different types of cells and its
      clinical consequences. To this end, we have examined the influence of different
      clinical and biochemical factors on erythrocyte membrane fluidity changes in
      psoriatic patients. Membrane fluidity was studied by the electron paramagnetic
      resonance spin-labeling method. The data revealed that the decrease of membrane
      fluidity corresponded with exacerbation of skin lesions. The results clearly
      indicate that the increased lipid peroxidation may be the essential mechanism of
      membrane fluidity decrease in psoriasis.

PMID- 11457644
TI  - Microchip electrophoretic separation systems for biomedical and pharmaceutical
      analysis.
AB  - The application of microchip capillary electrophoresis (CE) systems to biomedical
      and pharmaceutical analysis is described and reviewed. Fabrication,
      instrumentation, and operation of the systems are discussed. An overview of
      applications is presented, covering four main areas: DNA sequencing, genetic
      analysis, immunoassays, and protein and peptide analysis. These systems have the
      potential to dramatically change the way that biochemical analyses are performed.

PMID- 11457645
TI  - Model prodrugs designed for the intestinal peptide transporter. A synthetic
      approach for coupling of hydroxy-containing compounds to dipeptides.
AB  - The human peptide transporter, hPepT1, situated in the small intestine, may be
      exploited to increase absorption of drugs or model drugs by attaching them to a
      dipeptide, which is recognised by hPepT1. A synthetic protocol for this kind of
      model prodrugs was developed, in which model drugs containing a hydroxy group
      were attached to enzymatically stable dipeptides by hydrolysable ester linkages.
      Furthermore, a number of benzyl alcohols with various substituents in the 4
      position of the phenyl ring were coupled to D-Asp-Ala and D-Glu-Ala. Ideally, a
      prodrug should be stable in the upper small intestine and be converted to the
      parent drug during or after transport into the blood circulation. Therefore, we
      investigated the influence of the electronegativity of the substituent in the 4
      position of the phenyl ring on stability in aqueous solution at pH 6.0 and 7.4,
      corresponding to pH in jejunum and blood, respectively. In addition, the
      influence of the electronegativity of the substituent on stability upon storage
      was examined. Model prodrugs containing electron donating substituents in the 4
      position of the phenyl ring decomposed upon storage, while model prodrugs
      containing no substituents or electron withdrawing substituents in the 4-position
      were stable. In aqueous solution (pH 6.0 and 7.4), electron withdrawing
      substituents in the 4-position decreased the half-life of the model prodrug.
      These data provide important information on stability of this kind of model
      prodrugs upon storage and under aqueous conditions. The results may be applied in
      the rational design of oligopeptide ester prodrugs to obtain prodrugs, which are
      stable upon storage and have an optimal release profile of the drug.

PMID- 11457646
TI  - The role of P-glycoprotein in limiting intestinal regional absorption of digoxin
      in rats.
AB  - The objective of this work was to study the role of regional intestinal efflux
      activity of P-glycoprotein (Pgp) in situ in anesthetized rats in limiting the
      absorption of digoxin. A 10-cm portion of duodenum or jejunum, or 5-cm of colon
      was perfused single-pass with saline containing [(3)H]digoxin while the
      appearance of radioactivity in the blood was measured. Verapamil in the perfusate
      was used as a modulator of Pgp in the intestinal mucosa. Net water absorption,
      mucosal integrity, and intestinal motility of the isolated segment were
      monitored, as well as heart rate and blood pressure. Excretion of i.v.
      administered unlabelled digoxin, 1 mg/kg, into the intestine while perfusing the
      duodenum-proximal jejunum region, was studied for comparison. At a perfusate
      concentration of 1 mM, verapamil caused a dramatic increase in [(3)H]digoxin
      absorption rate from duodenum and jejunum, while the effect in colon was
      insignificant. At concentrations of 0.1, 1, and 2.5 mM in the duodenal perfusate,
      verapamil increased the absorption rate of [(3)H]digoxin in a dose-dependent
      manner. The lowest concentration almost doubled the rate without having any
      significant effects on the cardiovascular system, intestinal motility, or net
      absorption of water. The excretion rate of unlabelled digoxin from the blood into
      the gut lumen was found to be halved in the presence of 0.5 mM verapamil in the
      perfusate. Absorption rate of [(3)H]digoxin in the rat is likely limited by Pgp
      mediated efflux. The data indicate that Pgp plays an important role for digoxin
      efflux in the small intestine only.

PMID- 11457647
TI  - SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P
      glycoprotein-mediated multidrug resistance.
AB  - P-glycoprotein (P-gp) is the plasma membrane transport pump responsible for
      efflux of chemotherapeutic agents from cells and is one of the systems that
      secures multidrug resistance (MDR) of neoplastic cells. In the present study,
      drug sensitive L1210 and multidrug resistant L1210/VCR (characterized by
      overexpression of P-gp) mouse leukemic cell lines were used as an experimental
      model. We have found that SB203580, a specific inhibitor of p38-MAPK pathway,
      significantly reduced the degree of the vincristine resistance in L1210/VCR
      cells. This phenomenon was accompanied by a decrease in the LC(50) value of
      vincristine from 3.203+/-0.521 to 0.557+/-0.082 microM. The LC(50) value of
      sensitive cells for vincristine was about 0.011 microM. The effect of SB203580 on
      L1210/VCR cells was associated with significantly increased intracellular
      accumulation of [3H]-vincristine in the concentration dependent manner. Prolonged
      exposure of resistant cells to 30 microM SB203580 did neither significantly
      influence the gene expression of P-gp, nor change the protein levels of p38-MAPK.
      Western blot analysis revealed that the MDR phenotype in L1210/VCR cells was
      associated with increased level and activity of cytosolic p38-MAPK. In resistant
      cells, the enhanced phosphorylation of both, p38-MAPK and ATF-2 (endogenous
      substrate for p38-MAPK) was found as well. In conclusion we could remark that
      SB203580, an inhibitor of p38 kinase pathway, reversed the MDR resistance of
      L1210/VCR cells. MDR phenotype of these cells is connected with increased levels
      and activities of p38-MAPK. These findings point to the possible involvement of
      the p38-MAPK pathway in the modulation of P-gp mediated multidrug resistance in
      the L1210/VCR mouse leukemic cell line. However, the mechanisms of SB203580
      action should be further investigated.

PMID- 11457648
TI  - Lectin-functionalized liposomes for pulmonary drug delivery: effect of
      nebulization on stability and bioadhesion.
AB  - The generation of respirable aerosols of a functionalized colloidal carrier has
      been investigated in this study. Lectin-functionalized liposomes, which proved to
      show improved cell association (using A549 cell line and primary human alveolar
      cells) even in the presence of a commercial lung surfactant preparation, have
      been developed. The stability of non-functionalized liposomes during nebulization
      using a jet nebulizer (Pari II provocation nebulizer, operated using an air flow
      of 30 l/min) was firstly investigated, and the experimental and formulation
      conditions were optimized and applied for the preparation of lectin
      functionalized liposomes. The incorporation of cholesterol enhanced the stability
      of the liposomes during nebulization (from 15-20% leakage of a hydrophilic marker
      to 8% upon cholesterol incorporation) and upon incubation with lung surfactant
      preparation. Nebulization of the functionalized liposomes did not significantly
      influence their physical stability. Their enhanced cell binding capability
      (compared to non-functionalized liposomes) was also maintained. A drop in cell
      association compared to fresh functionalized liposomes was detected after
      nebulization, nevertheless, the binding was still significantly higher than that
      of the non-functionalized liposomes. The deposition of the liposomal preparation
      in lung periphery, proved by the deposition of the liposomal preparation on the
      lower stages of an ASTRA type cascade impinger and a mean median aerodynamic
      diameter (MMAD) of 2.85 microm, makes it a potential candidate as a macromolecule
      drug carrier for local and/or systemic administration.

PMID- 11457649
TI  - Minimal in vivo activation of CYP2C9-mediated flurbiprofen metabolism by dapsone.
AB  - Dapsone has been shown to activate flurbiprofen 4'-hydroxylation by expressed
      CYP2C9 enzyme and in human liver microsomes. It has been suggested that this
      observation is due to substrate cooperativity on enzyme activity; however, the in
      vivo relevance of this observation is unknown. Thus, the purpose of this study
      was to evaluate whether dapsone can act cooperatively with flurbiprofen to
      activate the in vivo metabolism of flurbiprofen to 4'-hydroxyflurbiprofen. Twelve
      healthy subjects received single-dose flurbiprofen 50 mg on three occasions:
      alone (visit A); 2 h after a single dapsone 100-mg dose (visit B); and 2 h after
      the seventh daily dose of dapsone 100 mg (visit C). Concentrations of
      flurbiprofen and 4'-hydroxy flurbiprofen in plasma and urine and dapsone and N
      acetyldapsone in plasma were determined by HPLC. Flurbiprofen pharmacokinetic
      parameters for the three visits were estimated by non-compartmental methods and
      compared in the absence and presence of dapsone. Flurbiprofen apparent oral
      clearance was increased by approximately 11% (P < 0.02) after dapsone 100 mg for
      7 days. Dapsone plasma concentrations averaged 5 +/- 2 microM after a single dose
      and 11 +/- 4 microM after seven daily 100 mg doses. These dapsone plasma
      concentrations were within the range of concentrations producing activation of
      flurbiprofen metabolism by CYP2C9 in vitro. These results are consistent with the
      hypothesis that dapsone does influence flurbiprofen metabolism in vivo in a
      cooperative way to enhance metabolism. However, the magnitude of effect is
      substantially less than observed in vitro.

PMID- 11457650
TI  - Local anaesthetic block copolymer system undergoing phase transition on dilution
      with water.
AB  - The possibility of formulating a local anaesthetic system displaying in situ
      gelation on dilution with water, as well as its dependence on concentration of
      active ingredients and pH was investigated. For this purpose Lutrol F68, water, a
      eutectic mixture of lidocaine and prilocaine and Akoline MCM were mixed in
      different ratios and investigated using crossed polarisers, small-angle X-ray
      diffraction, rheology, conductivity and NMR self-diffusion measurements. In
      particular, an isotropic phase of low viscosity turning into a high viscous
      hexagonal phase upon dilution with water was found. The increase in viscosity is
      only weakly dependent on temperature in the temperature range of 20-37 degrees C.
      The rheology and in vitro drug release of these systems were studied and the
      elastic modulus was found to be fairly independent of concentration of active
      ingredients and pH in the investigated region. The in vitro release of lidocaine
      and prilocaine was found to increase with increasing concentration of the active
      ingredients and with decreasing pH, the latter as a consequence of the pH
      dependent ionisation of these substances. The behaviour of the system is
      promising from a pharmaceutical point of view, since the isotropic low-viscous
      phase can be injected into, e.g. a periodontal pocket where the presence of
      saliva will cause a temporal transition into a rigid hexagonal phase thus making
      the formulation stay at the application site. At even higher water content,
      either as a result of longer application time or rinsing with water, the
      hexagonal phase is effectively dissolved through transformation to a water-rich
      micellar phase.

PMID- 11457651
TI  - Topically applied liposome encapsulated superoxide dismutase reduces postburn
      wound size and edema formation.
AB  - The overproduction of biochemical mediators, and activation of leukocytes and
      endothelial cells, generated in thermally injured tissue, gives rise to both
      local and distant effects. The formation of short-lived, highly reactive
      metabolites, such as oxygen free radicals, increases with increasing tissue
      ischemia, and causes further cell damage. Human recombinant Cu/Zn-superoxide
      dismutase (rh-Cu/Zn-SOD), an enzyme which captures these radicals, may have a
      beneficial effect on the postburn inflammation processes. In this study, the
      influence of rh-Cu/Zn-SOD application to thermally injured tissue of rabbit
      backskin was examined. Three different delivery strategies were compared, pure or
      liposomally encapsulated enzyme, or intralesionally injected rh-Cu/Zn-SOD. For
      control, one animal group was treated with plain gel and another group was kept
      untreated. At 24 h following trauma a statistically significant difference in
      lesion sizes between the enzyme treated and control groups was observed. After 72
      h tissue swelling had diminished significantly more in the rh-Cu/Zn-SOD treated
      groups as compared to the control animals. The best results were achieved by
      spreading liposomes encapsulating the enzyme onto the wounds. Our results suggest
      that local treatment of burn wounds with enzymatic radical scavengers such as rh
      Cu/Zn-SOD has a beneficial effect on the extent of the postburn damage.

PMID- 11457652
TI  - Nasal bioavailability of peptide T in rabbits: absorption enhancement by sodium
      glycocholate and glycofurol.
AB  - The aim of the present study was to investigate the absolute nasal
      bioavailability of Peptide T from aqueous formulations containing sodium
      glycocholate, an absorption enhancer with known effect on epithelial tight
      junctions, and/or glycofurol in a crossover study in rabbits. Additionally, the
      reversibility of the absorption enhancing effect of sodium glycocholate was
      studied by applying enhancer and peptide T with different time intervals and
      calculating Area Under the Curve of the peptide in plasma. It was shown that the
      bioavailability of Peptide T was significantly enhanced when glycofurol or sodium
      glycocholate was added to a nasal formulation. The nasal bioavailability of
      Peptide T in water (control formulation), 5% glycofurol, 5% glycofurol+1% sodium
      glycocholate and 1% sodium glycocholate was 5.9, 22, 29 and 59%, respectively. As
      indicated by the differences in t(max), C(max) and time-concentration profiles
      different patterns of Peptide T absorption were seen from the vehicles containing
      glycofurol and sodium glycocholate. In the reversibility study, the enhancing
      effect of sodium glycocholate on nasal absorption of Peptide T was found to be
      reversible within 4 h. It was concluded, that nasal absorption of Peptide T in
      rabbits was effectively enhanced by co-administration of sodium glycocholate,
      which also provided very fast absorption rates as well as a relatively short
      lasting effect of the absorption enhancing effect. Co-administration of
      glycofurol leads to enhanced and prolonged absorption of the peptide. Combining
      the two enhancers did not lead to increased peptide T absorption compared to 5%
      glycofurol alone.

PMID- 11457653
TI  - Levels of dopamine in blood and brain following nasal administration to rats.
AB  - The aim of this study was to investigate the levels of [(3)H]dopamine in blood,
      the cerebrospinal fluid (CSF) and brain tissue samples in rats and to find out
      whether the drug is transferred along the olfactory pathway to the central
      nervous system following nasal administration. [(3)H]Dopamine (50 microCi) was
      given to male Sprague-Dawley rats either intravenously or nasally to the right
      nostril. For the absorption study, blood samples were withdrawn from the carotid
      artery. The CSF samples were taken by cisternal puncture and then brain tissue
      samples were excised. The presence of unchanged dopamine in the samples was
      ascertained using thin layer chromatography (TLC). The radioactivity in the
      samples was measured using liquid scintillation. The greatest amount of the total
      radioactivity absorbed from the nasal mucosa into the systemic circulation was
      observed at the first sampling point 15 min after administration. The
      bioavailability of the total radioactivity was 68+/-30%. The uptake of
      [(3)H]dopamine in the brain was significantly higher 30 min after nasal
      administration than after intravenous administration (P<0.01). TLC data showed
      that approximately 59%, 14% and 68% of the radioactivity in the olfactory bulb,
      CSF and olfactory mucosa, respectively, coeluted with dopamine. In conclusion,
      these results show that unchanged dopamine is transferred into the olfactory bulb
      via the olfactory pathway in rats.

PMID- 11457654
TI  - Active efflux of the 5-HT(1A) receptor agonist flesinoxan via P-glycoprotein at
      the blood-brain barrier.
AB  - The role of P-glycoprotein on the efflux of the 5-HT(1A) receptor agonist
      flesinoxan across the blood-brain barrier in vivo and in vitro was investigated.
      In vitro, the transport ratios (representing polarized transport) of flesinoxan
      (10 microg/ml) were 4.2 in the MDR1-transfected LLC-PK1 cell line, which could be
      inhibited by the Pgp modulators SDZ-PSC 833 and LY 335979 and 1.1 in the wild
      type LLC-PK1 cell line after 4 h. Flesinoxan concentrations lower than 33
      microg/ml were actively transported by Pgp, while at higher concentrations Pgp
      became saturated and transport in the MDR1-transfected cell line was comparable
      with the wild-type cell line. In the in vitro BBB co-culture model the transport
      ratio was 2.0 and was decreased to 1.0 in the presence of Pgp modulators. In
      vivo, the accumulation of flesinoxan in the brain at 3 h was much higher in the
      mdr1a(-/-) mice compared to mdr1a(+/+) mice (ratio 12.6 and 27.0 at dose levels
      of 3 mg/kg and 10 mg/kg respectively). In conclusion, both in vivo as well as in
      vitro results have demonstrated that Pgp is a limiting factor for the transport
      of the 5-HT(1A) receptor agonist flesinoxan into the CNS. This should be
      considered when its application in therapy is combined with other Pgp substrates.

PMID- 11457655
TI  - Sensitivity of an empirical affinity scoring function to changes in receptor
      ligand complex conformations.
AB  - A combination of empirical scoring and conformational sampling for ligand binding
      affinity prediction is examined. The behaviour of a scoring function with respect
      to the sensitivity to conformational changes is investigated using ensembles of
      structures generated by molecular dynamics simulation. The correlation between
      the calculated score and the coordinate deviation from the experimental structure
      is clear for the complex of arabinose with arabinose-binding protein, which is
      dominated by hydrogen bond interactions, while the score calculated for the
      hydrophobic complex between retinol and retinol binding protein is rather
      insensitive to ligand conformational changes. For typical ensembles of structures
      generated by molecular dynamics at 300 K, the variation of the calculated score
      is considerably smaller than that of the underlying molecular mechanics
      interaction energies.

PMID- 11457656
TI  - Molecular mechanisms of glucocorticoid action in rheumatic autoimmune diseases.

PMID- 11457657
TI  - Involvement of cyclic AMP response element binding protein (CREB) and estrogen
      receptor phosphorylation in the synergistic activation of the estrogen receptor
      by estradiol and protein kinase activators.
AB  - Estrogen receptor (ER) and cAMP signaling pathways interact in a number of
      estrogen target tissues including mammary and uterine tissues. One aspect of this
      interaction is that estradiol and protein kinase A (PKA) activators can cooperate
      synergistically to activate ER-mediated transcription of both endogenous genes
      and reporter genes containing only estrogen response elements. The purpose of
      this study was to investigate the molecular mechanism of this interaction between
      signaling pathways. Site-directed mutagenesis of the potential PKA
      phosphorylation sites in the ER indicated that phosphorylation of these sites was
      not necessary for the observed transcriptional synergy. In transient transfection
      assays in two different cell lines using reporter constructs containing either
      cAMP response elements, estrogen response elements or both types of elements,
      with the addition or absence of cAMP response element binding protein (CREB)
      expression plasmid, we observed that only one of these cell lines exhibited
      estrogen/PKA transcriptional synergy. Experiments demonstrated that CREB itself
      was involved in the transcriptional synergy, and that transfection of CREB
      restored transcriptional synergy in the cell line in which it was lacking. A
      functional interaction between ER and CREB was also demonstrated using a
      mammalian cell protein interaction assay; a dominant negative mutant of CREB did
      not exhibit this interaction. Therefore, these data indicate that CREB protein is
      required for the transcriptional synergy between cAMP and estrogen signaling
      pathways. Furthermore, CREB cooperated with the ER on genes that did not contain
      cAMP response elements, but contained only estrogen response elements. We propose
      that activated CREB is recruited to estrogen responsive genes by an ER-
      coactivator complex containing proteins such as CREB binding protein (CBP) and
      that the interaction of CREB with ER may assist in stabilizing its interaction
      with CBP and in promoting estrogen-ER and PKA transcriptional synergy.

PMID- 11457658
TI  - A non-calcemic analog of 1 alpha,25 dihydroxy vitamin D(3) (JKF) upregulates the
      induction of creatine kinase B by 17 beta estradiol in osteoblast-like ROS 17/2.8
      cells and in rat diaphysis.
AB  - We have reported that multiple treatments with so-called 'non-hypercalcemic'
      analogs of 1 alpha,25(OH)(2) vitamin D(3) (1,25(OH)(2)D(3)) stimulate the
      specific activity of creatine kinase BB (CK) in ROS 17/2.8 osteoblast-like cells,
      and that pretreatment with these analogs upregulates responsiveness and
      sensitivity to 17 beta estradiol (E(2)) for the induction of CK. However, since
      the analogs showed toxicity in vivo, we have now studied the action of a
      demonstrably non-calcemic hybrid analog of vitamin D in ROS 17/2.8 cells, and
      prepubertal rats. The analog JKF was designed to separate its calcemic activity
      from other biological activities by combining a calcemic-lowering 1-hydroxymethyl
      group with a potentiating C, D-ring side chain modification including 24
      difluoronation. Treatment with 1 pM JKF alone significantly stimulated CK
      specific activity at 4 h by 30+/-10%. However after three daily pretreatments,
      JKF upregulated the extent of induction by 30 nM E(2) by 33% at 1 pM and by 97%
      at 1 nM; the E(2) dose needed for a significant stimulation of CK activity was
      lowered to 30 pM. The action of the SERMS tamoxifen, tamoxifen methiodide and
      raloxifene, at 3 microM, was also upregulated by three daily pretreatments with 1
      nM JKF; unexpectedly, this pretreatment prevented the inhibition of E(2)
      stimulation by the SERMS. Upregulation of E(2) action by 1 nM JKF was inhibited
      by 1 nM ZK159222, an inhibitor of the nuclear action of 1,25(OH)(2)D(3). In vivo,
      three daily injections of 0.05 ng/g body weight of JKF augmented the response of
      prepubertal female rat diaphysis and epiphysis to E(2). Therefore, demonstrably
      non-calcemic analogs of 1,25(OH)(2)D(3) may have potential for use in combination
      with estrogens or SERMS in the prevention and/or treatment of metabolic bone
      diseases such as postmenopausal osteoporosis.

PMID- 11457659
TI  - Synergistic anti-proliferative effects of vitamin D derivatives and 9-cis
      retinoic acid in SH-SY5Y human neuroblastoma cells.
AB  - This study examines the effect of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)],
      24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)], two vitamin D analogues (KH 1060
      and EB 1089, which are 20-epi-22-oxa and 22,24-diene-analogues, respectively), 9
      cis retinoic acid and all-trans retinoic acid on proliferation of SH-SY5Y human
      neuroblastoma cells, after treatment for 7 days. Cell number did not change when
      the cells were incubated with 1, 10 or 100 nM 1,25(OH)(2)D(3) or its derivatives,
      but significantly decreased in the presence of the two retinoids (0.001--10
      microM final concentration). A synergistic inhibition was observed, when SH-SY5Y
      cells were treated combining 0.1 microM 9-cis retinoic acid and 10 nM
      1,25(OH)(2)D(3) or 10 nM KH 1060, and 1 microM 9-cis retinoic acid and 10 nM
      1,25(OH)(2)D(3) or 10 nM EB 1089. Acetylcholinesterase activity showed a
      significant increase, in comparison with controls, after treatment of the cells
      for 7 days with 0.1 or 1 microM 9-cis retinoic acid, alone or combined with 10 nM
      1,25(OH)(2)D(3) or 10 nM KH 1060 or 10 nM EB 1089. This increase was synergistic,
      combining 1 microM 9-cis retinoic acid and 10 nM 1,25(OH)(2)D(3) or EB 1089. The
      levels of the c-myc encoded protein remarkably decreased after treatment of SH
      SY5Y cells for 1, 3, 7 days with 0.1 and 1 microM 9-cis retinoic acid, alone or
      combined with 10 nM 1,25(OH)(2)D(3) or 10 nM KH 1060 or 10 nM EB 1089. In
      particular, the association of 1 microM 9-cis retinoic acid and 10 nM
      1,25(OH)(2)D(3) or 10 nM EB 1089 resulted in a synergistic c-myc inhibition, in
      comparison with that obtained in the presence of the retinoid alone. These
      findings may have therapeutic implications in human neuroblastoma.

PMID- 11457660
TI  - Comparative biosynthetic pathway of androstenol and androgens.
AB  - It has been shown recently that androstenol and androstanol could modulate gene
      expression through the nuclear orphan receptors CAR (constitutive androstane
      receptor) and PXR (pregnane X receptor). Although, in the pig, androstenol is
      produced in high amounts and is active as a pheromone, its role in the human is
      ill defined. Androstenol possesses a structure similar to that of androgens, with
      the exception that it does not possess an oxygen at position 17 that is crucial
      for androgenic and estrogenic activity. It has been shown that human and boar
      testis homogenates could produce androstenol, but details of the biosynthetic
      pathway had not yet been elucidated. It has also been shown recently that
      androstenol could modulate the activity of CAR and PXR and the expression of some
      cytochrome P450 drug-metabolizing enzymes. We wanted to determine the precise
      biosynthetic pathway of androstenol and other closely related steroids. Using
      transformed human embryonic kidney (HEK-293) cells that stably express 3 beta
      hydroxysteroid dehydrogenase, 5 alpha-reductase and 3 alpha-hydroxysteroid
      dehydrogenase, we have shown that these enzymes are able to efficiently transform
      the precursor 5,16-androstadien-3 beta-ol into androstenol. We thus provided
      evidence that androstenol, the ligand for CAR and PXR, is produced by the
      biosynthetic pathway of sex steroids.

PMID- 11457661
TI  - Common phytochemicals are ecdysteroid agonists and antagonists: a possible
      evolutionary link between vertebrate and invertebrate steroid hormones.
AB  - Many plant compounds are able to modulate growth and reproduction of herbivores
      by directly interacting with steroid hormone systems. In insects, several classes
      of phytochemicals, including the phytoestrogens, interfere with molting and
      reproduction. We investigated whether the anti-ecdysone activity may be due to
      interaction with the ecdysone receptor (EcR) using a reporter-gene assay and a
      cell differentiation assay of an ecdysone-responsive cell line, Cl.8+. We tested
      rutin (delays molt in insects); four flavones: luteolin and quercetin
      (metabolites of rutin), and apigenin and chrysin; and three non-flavones,
      coumestrol and genistein (both estrogenic) and tomatine (alters molt in insects).
      None of the phytochemicals tested were ecdysone agonists in the reporter-gene
      assay, but the flavones were able to significantly inhibit EcR-dependent gene
      transcription. In the Cl.8+ cells, quercetin and coumestrol were mixed
      agonists/antagonists, while genistein, tomatine and apigenin showed a synergistic
      effect with ecdysteroid in the reduction of cell growth. We suggest that the
      rutin effects on molting in insects are most likely due to the metabolites,
      luteolin or quercetin, while tomatine acts via a non-EcR pathway. Flavones not
      only interact with EcR and estrogen receptor (ER), but also signal nitrogen
      fixing bacteria to form root nodules. The NodD protein which regulates this
      symbiosis has two ligand-binding domains similar to human ERalpha. The
      evolutionary significance of these findings are discussed.

PMID- 11457662
TI  - Isolation and characterization of the monkey UDP-glucuronosyltransferase cDNA
      clone monUGT1A01 active on bilirubin and estrogens.
AB  - Although enzymes that catalyze the formation of steroids are well known, less
      information is available about the enzymes involved in the metabolism of these
      hormones. Steroid glucuronidation, by UDP-glucuronosyltransferase enzymes, is one
      mechanism by which steroid hormones can be metabolized and eliminated from a
      tissue. Previous results suggest that the monkey represents the most appropriate
      animal model for studying the physiologic relevance of steroid glucuronidating
      enzymes. The monkey UGT1A01 cDNA clone was isolated by RT-PCR amplification of
      the liver RNA. The cDNA contains an open reading frame of 1599 bp encoding a
      protein of 533 residues. The primary structure of monkey UGT1A01 is 95% identical
      to human UGT1A1. To compare monkey and human UGT1A1 enzymes, both cDNA clones
      were transfected into HK293 cells and stable cell lines expressing each UGT1A1
      protein were established. Western blot analysis of the monUGT1A01-HK293 and
      hUGT1A1-HK293 cell lines using a anti-UGT1A polyclonal antibody (RC-71) revealed
      expression of exogenous 55 kDa UGT1 proteins. The transferase activities of
      monkey and human UGT1A1 proteins were tested with over 60 compounds and were
      demonstrated to be active on the same compounds. For endogenous compounds only
      bilirubin and C18 steroids were glucuronidated by these enzymes. Using microsome
      preparation (from HK293 cell expressing monkey UGT1A01), the apparent K(m) values
      were 13, 5 and 6 microM for the conjugation of estradiol, 2-hydroxyestradiol and
      2-hydroxyestrone, respectively, and were very similar to the values obtained with
      human UGT1A1. Specific RT-PCR analysis demonstrated the expression of monkey and
      human UGT1A1 transcripts in several tissues including liver, kidney, intestine,
      prostate, testis and ovary suggesting a contribution of this isoenzyme to
      estrogen metabolism in the cynomolgus monkey as in human.

PMID- 11457663
TI  - Evidence for the involvement of nitric oxide in the control of steroid secretion
      by the frog adrenal gland.
AB  - Nitric oxide (NO) has been found to modulate the response of rat, bovine and
      human adrenocortical cells to corticotropic factors. The aim of the present study
      was to investigate the possible involvement of NO in the control of
      corticosteroid secretion in the frog Rana ridibunda. Histochemical studies using
      the NADPH-diaphorase reaction and immunohistochemical labeling with antibodies
      against NO synthase (NOS) revealed that NOS is exclusively expressed in
      chromaffin cells. The NO donor sodium nitroprusside (SNP) and the NO synthase
      inhibitor Nw-nitro-L-arginine (L-NO(2)Arg) did not modify the spontaneous
      production of corticosterone and aldosterone by perifused adrenal slices.
      Similarly, L-NO(2)Arg had no effect on the secretory responses induced by ACTH,
      angiotensin II (AII) and endothelin-1 (ET-1). In contrast, SNP significantly
      inhibited the stimulatory effects of ACTH, AII and ET-1 on corticosterone and
      aldosterone secretion. These data provide the first evidence for a modulatory
      role of NO on adrenocortical cell activity in amphibians.

PMID- 11457664
TI  - Expression and characterization of the human 3 beta-hydroxysteroid
      sulfotransferases (SULT2B1a and SULT2B1b).
AB  - The human hydroxysteroid sulfotransferase, dehydroepiandrosterone
      sulfotransferase (DHEA-ST), is highly expressed in liver and adrenal cortex and
      displays reactivity towards a broad range of hydroxysteroids including 3 beta
      hydroxysteroids, 3 alpha-hydroxysteroids, estrogens with a 3-phenolic moiety, and
      17-hydroxyl group of androgens. In contrast, characterization of the newly
      described human hydroxysteroid sulfotransferase SULT2B1 isoforms shows that these
      enzymes are selective for the sulfation of 3 beta-hydroxysteroids, such as
      pregnenolone, epiandrosterone, DHEA, and androstenediol. There was no activity
      detected towards testosterone, dexamethasone, beta-estradiol, androsterone, or p
      nitrophenol. The SULT2B1 gene encodes two isoforms, SULT2B1a and SULT2B1b, which
      are generated by alternate splicing of the first exon; therefore the SULT2B1
      isoforms differ at their N-terminals. Northern Blot analysis detected a SULT2B1
      message in RNA isolated from the human prostate and placenta. No SULT2B1 message
      was observed in RNA isolated from human liver, colon, lung, kidney, brain, or
      testis tissue. Purified SULT2B1a was used to generate a specific rabbit
      polyclonal anti-SULT2B1 antibody. The anti-SULT2B1 antibody did not react with
      expressed human EST, P-PST-1, M-PST, DHEA-ST, or ST1B2, during immunoblot
      analysis. The substrate specificity of the expressed SULT2B1 isoforms suggests
      that these enzymes are capable of regulating the activity of adrenal androgens in
      human tissues via their inactivation by sulfation.

PMID- 11457665
TI  - In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer.
AB  - Ospemifene (FC-1271a) is a novel selective estrogen receptor modulator under
      development for osteoporosis prevention. In the present paper, we examine both
      the in vitro and in vivo effects of FC-1271a in breast cancer models. In vitro,
      the growth inhibitory effects of FC-1271a and its main metabolite are
      investigated in MCF-7 and MDA-MB-231 human breast cancer cells at doses ranging
      from 0.1 to 10 microM. Modulation of pS2 expression, an indicator of estrogen
      activity, was also examined in all experiments using reverse transcription
      polymerase chain reaction. In vivo, the effects of treatment with 10, 25, 50, or
      100 mg/kg FC-1271a on MCF-7 and MDA-MB-231 human tumor xenografts in athymic,
      ovariectomized mice were determined. For MCF-7 cells, FC-1271a and its main
      metabolite, toremifene VI (TOR VI) displayed anti-estrogenic effects in vitro as
      shown through growth inhibition and decreased expression of pS2. Treatment with
      FC-1271a in vivo inhibited MCF-7 tumor growth, compared with control (P< or
      =0.05). FC-1271a and TOR VI did not inhibit the growth of MDA-MB-231 cells in
      vitro, and no clear effects of FC-1271a treatment were seen on MDA-MB-231 tumor
      growth in vivo. In conclusion, FC-1271a appears to exert anti-estrogenic effects
      dependent on estrogen receptor positivity in vitro and in vivo on the growth of
      MCF-7 cells.

PMID- 11457666
TI  - ICI 182,780 acts as a partial agonist and antagonist of estradiol effects in
      specific cells of the sheep uterus.
AB  - We assessed the ability of ICI 182,780 (ICI) to block the estradiol (E2)
      responses of genes within the sheep uterus. Ovariectomized ewes in the 'ICI+E2'
      treatment group received a uterine infusion with 10(-7) M ICI for 14 h, an
      injection of 50 microg E2 6 h after the infusion started, and were
      hysterectomized 18 h postinjection. Other groups received only ICI or E2, or
      neither treatment ('Con'). Both E2 and ICI increased the wet weight of dissected
      endometrium: averaging 10.0+/-1.2 g for ICI+E2, ICI, and E2 groups compared to
      6.8+/-0.6 g for Con. Slot blot analyses of endometrial RNA showed that estrogen
      receptor-alpha (ER), progesterone receptor (PR), glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH), cyclophilin, actin and c-fos mRNAs responded to E2
      treatment: the first five increased an average of 60% while the last decreased
      38%. In situ hybridization identified more subtle ICI effects: agonistic up
      regulation of GAPDH mRNA in superficial endometrial cells, and antagonistic down
      regulation of ER and PR mRNAs in the inner layer of the myometrium. Thus, we
      conclude that the agonist versus antagonist effects of ICI relative to those of
      E2 are a function of the gene examined as well as the specific cell within the
      uterus.

PMID- 11457667
TI  - Fasting plasma glucose diagnostic criterion, proposed by the American Diabetes
      Association, has low sensitivity for diagnoses of diabetes in Mexican population.
AB  - To determine the best cutoff value of fasting plasma glucose (FPG) for diagnosis
      of diabetes, using the 2-h postglucose load (2-h PG) as the gold standard, in
      Mexican population and compare it to the 7.0 mmol/l limit proposed by the
      American Diabetes Association (ADA). 712 apparently healthy Mexican individuals
      were included in a cross-sectional randomized population survey. Sensitivity of
      FPG criterion for diagnoses of type 2 diabetes was calculated from a fourfold
      table. Glycemia value 2-h PG of >or=11.1 mmol/l was the "gold standard"
      diagnostic test. The optimal FPG value for diagnoses of diabetes was established
      on a receiver operating characteristic (ROC) scatter plot. On the basis of the
      "gold standard" diagnostic test, diagnosis of type 2 diabetes was established in
      65 (9.12%) subjects, whereas the ADA FPG diagnostic criterion only identified 39
      (5.47%) subjects; that is a sensitivity of 60% (CI(95%) 47.1-72.0). The ROC
      scatter plot showed the best cutoff value of FPG for diagnoses of diabetes that
      corresponds to 6.1 mmol/l, which has the highest sensitivity (0.985). FPG
      diagnostic criterion proposed by the ADA Expert Committee for diagnosis of type 2
      diabetes has low sensitivity in Mexican population. For epidemiological purposes,
      estimates of diabetes prevalence in Mexico based on a FPG value of >or=6.1 mmol/l
      will improve the success of the screening.

PMID- 11457668
TI  - Cardiovascular structure and function in baboons with Type 1 diabetes -- a
      transvenous ultrasound study.
AB  - Diabetes mellitus is an important risk factor for both macrovascular and cardiac
      disease in humans. The availability of a novel intravenous ultrasound probe
      allows detailed interrogation of a large proportion of the vasculature, as well
      as the heart, during the same examination. Six male baboons (Papio hamadryas)
      with Type 1 diabetes and known microangiopathy, and six control animals were
      studied. Vascular structure in the major large arteries and cardiac function were
      studied using transvenous ultrasound introduced via the right femoral vein and
      positioned under fluoroscopy. All arteries were examined for atherosclerotic
      plaque and for presence of increased intima-media thickness (IMT). Left
      ventricular function was assessed at rest and following infusions of dobutamine
      (positive inotrope) and esmolol (negative inotrope). The procedure was performed
      safely and successfully in all cases. No atherosclerotic plaque was seen in
      either diabetic or normal baboons. There was no difference in the aortic IMT
      (0.38+/-0.04 vs. 0.37+/-0.05 mm, normal vs. diabetic, P=NS) or in doppler flow in
      the renal or iliac arteries between diabetic and normal baboons. Left ventricular
      wall thickness and systolic tissue velocity were similar in the two groups at
      rest (6.9+/-2.5 vs. 6.2+/-1.4 cm/s, normal vs. diabetic, P=NS), after dobutamine
      (15.5+/-2.2 vs. 12.7+/-3.9 cm/s, normal vs. diabetic, P=NS), and after esmolol
      (4.3+/-1.0 vs. 5.6+/-1.0 cm/s, normal vs. diabetic, P=NS). In a high primate
      model of diabetes with microangiopathy, the presence of hyperglycemia for 7 years
      per se does not produce abnormalities of macrovascular or cardiac structure.

PMID- 11457669
TI  - Association of adiposity assessed by means of near-infrared interactance with the
      beta-cell function, insulin resistance and leptin concentrations in non-obese
      subjects. Exploratory study.
AB  - The objective was to identify the association of adiposity with the beta-cell
      function, insulin resistance and leptin concentrations in non-obese subjects.
      Twenty-eight healthy, non-obese volunteers were recruited, 14 male and 14 female.
      Body mass index (BMI) and waist hip ratio (WHR) were calculated. Blood pressure
      was measured. Adiposity was estimated by means of near-infrared (NIR)
      interactance method predicting the percentage of body fat (% BF). All subjects
      were divided into adipose and non-adipose individuals. Serum glucose, insulin and
      leptin levels were measured. Formulas of the homeostasis model analysis were used
      to assess the insulin resistance and the beta-cell function. Clinical
      characteristics and laboratory profile were similar between both groups. There
      were no significant differences between both groups in beta-cell function,
      insulin resistance and leptin concentrations. There was a positive significant
      correlation of % BF with BMI in women (r= .82, P< .001) and in men (r= .85, P<
      .001). Adiposity was not associated with the beta-cell function, insulin
      resistance and leptin concentrations in non-obese subjects, and only percent body
      fat was positive correlated with BMI.

PMID- 11457670
TI  - Polymorphisms in the RAGE gene influence susceptibility to diabetes-associated
      microvascular dermatoses in NIDDM.
AB  - To examine genetic polymorphism in the complete sequence of the Receptor of
      Advanced Glycation End products (RAGE) gene and its possible associations with
      diabetes-associated microvascular dermatoses (DAMD). Further, to analyze the
      distribution of individual genotype combinations on the particular polymorphic
      loci in the RAGE gene. A part of the RAGE gene spanning a region from -4 to 3334
      bp was analyzed on a set of 45 subjects with non-insulin dependent diabetes
      mellitus (NIDDM) and parallel DAMD by means of PCR with subsequent heteroduplex
      and single-strand conformation polymorphism (SSCP) analyses. Allele frequencies
      and genotype combinations of novel common polymorphisms were determined in an
      associations study comprising four groups of subjects (n=390). Fourteen novel
      polymorphisms (R77C, V89V, 718G/T, 1704G/T, 1727A1728ins, H305Q, S307C, 2117A/G,
      2184A/G, 2245G/A, 2249A/G, 2741G/A, and 3089ACdel) and one described previously
      (G82S) were identified. Significant association with microvascular dermatoses
      (MD) irrespective of NIDDM were found for exon mutation 82S (P= .004, after a
      correction for the number of comparisons P(corr) < .05) and marginally
      significant for intron variant 1704T (P= .032, P(corr)> .05). Calculated odds
      ratios for 82S and 1704T were 4.73 (95% CI, 1.51 to 14.77) and 1.73 (95% CI, 0.93
      to 3.22), respectively. Certain individual genotype combinations of G82S,
      1704G/T, and 2184A/G were significantly associated with the presence of MD (P=
      .00647) both in diabetic and non-diabetic study populations. The two novel
      polymorphisms (1704G/T and 2184A/G) together with the G82S were shown to
      influence the susceptibility to MD independent of diabetes itself.

PMID- 11457671
TI  - High glucose levels enhance TGF-beta1-thrombospondin-1 pathway in cultured human
      mesangial cells via mechanisms dependent on glucose-induced PKC activation.
AB  - We have previously demonstrated that thrombospondin-1 (TSP-1) promotes activation
      of latent TGF-beta1 in cultured human mesangial cells (MCs) [Nephron 79 (1998)
      38.]. This study was performed to clarify the relationship between protein kinase
      C (PKC) activity and activation of TGF-beta1 and TSP-1 production in cultured
      human MCs exposed to high glucose levels. MCs grown in 33 mmol/l glucose
      demonstrated a significant (P< .01) increase in activation of TGF-beta1 compared
      with those in 5 mmol/l glucose, which were evaluated by both an ELISA and a
      bioassay. High glucose-induced increase in active TGF-beta1 was completely
      inhibited by coincubation with 5 micromol/l GFX, a PKC inhibitor, and was
      mimicked by the addition of 0.1 micromol/l phorbol 12,13-dibutyrate (PDBu). On
      the other hand, increased TSP-1 production from MCs stimulated by 0.1 nmol/l
      recombinant TGF-beta1 and 0.1 micromol/l PDBu were significantly (P< .01) reduced
      by the addition of 10 nmol/l latency-associated peptide (LAP), a specific
      inhibitor of TGF-beta1 activity. The amount of TSP-1 secreted from MCs increased
      by a high ambient glucose. The glucose-induced increase in TSP-1 production was
      markedly attenuated by the treatment with GFX and LAP, while those agents did not
      affect TSP-1 production in low-glucose concentrations. Taken together, our
      results suggest that glucose-induced activation of TGF-beta1 is dependent on PKC
      activity, leading to a sequential increase in TSP-1 synthesis in cultured human
      MCs. Thus, we propose that high glucose conditions induce an increase in PKC-TGF
      beta1 activity-TSP-1 pathway, and that glucose-induced increase in TSP-1 may
      synergistically facilitate TGF-beta1 activation in an autocrine manner in MCs.

PMID- 11457672
TI  - Diabetes causes an early reduction in autonomic ganglion blood flow in rats.
AB  - Impaired blood flow to peripheral nerve trunks makes a major contribution to the
      neuropathic complications of diabetes mellitus. Comparatively little attention
      has been paid to perfusion abnormalities for the cell bodies of origin of the
      autonomic and sensory nerves, although they are severely affected in diabetic
      neuropathy. The aim was to examine the time course of changes in superior
      cervical ganglion (SCG) perfusion in streptozotocin-induced diabetic rats.
      Ganglion blood flow, measured by hydrogen clearance microelectrode polarography,
      was approximately 70 ml min(-1) 100 g(-1). One week of diabetes caused a 46%
      perfusion deficit, which was maintained (54%) over 24 weeks. Thus, an early,
      profound, and long-lived reduction in ganglion perfusion may deleteriously affect
      neural cell body function and could contribute to autonomic neuropathy.

PMID- 11457673
TI  - Pathophysiology of oxidative stress in diabetes mellitus.
AB  - Oxidative stress is believed to play an important role, albeit not fully
      recognized, in the development of vascular complications in diabetes mellitus
      (DM) particularly type 2. In the majority of studies, attention was focused on
      lipid oxidation, specifically on that of low-density lipoproteins (LDLs). More
      recent investigations have revealed that it is not only the lipid but also the
      apolipoprotein moiety of LDL that becomes oxidatively modified resulting in the
      formation of insoluble aggregates. Consequently, it has been documented that LDL
      aggregation was due to the hydroxyl radical-induced dityrosine crosslinking
      between apo B monomers. In DM patients with atherosclerotic complications,
      intravascular fibrous deposits were shown to contain, in addition to oxidized
      LDL, a fibrin-like material (FLM). This material is immunologically identical to
      fibrin that is normally formed as a result of intravascular activation of the
      blood coagulation cascade. Although DM patients with vascular disease display
      increased concentration of plasma fibrinogen (Fbg), the precursor of fibrin, no
      markers of full blown activation of blood coagulation could be found.

PMID- 11457675
TI  - Introduction: cardiovascular syncope in infants and children.

PMID- 11457674
TI  - Treating dyslipidaemia in non-insulin-dependent diabetes mellitus -- a special
      reference to statins.
AB  - Patients with non-insulin-dependent diabetes (NIDDM) have an increased incidence
      of ischaemic heart disease (IHD) when compared with nondiabetic subjects. In
      addition, they have a worse prognosis after their first myocardial infarction
      (MI). According to the recent USA recommendations, the threshold for initiation
      of dietary intervention in diabetic subjects is an LDL greater than 2.6 mmol/l,
      with the goal to achieve levels less than 2.6 mmol/l (100 mg/dl). This is also
      the threshold for initiation and treatment goal for pharmacological intervention
      in diabetic subjects, unless they are completely free of IHD, peripheral vascular
      disease or cerebrovascular disease and have no other IHD risk factors. In the
      latter circumstances, the threshold for treatment is an LDL greater than 3.38
      mmol/l (130 mg/dl), with the goal to achieve levels less than 3.38 mmol/l. The
      HMG-CoA reductase inhibitors (statins) can improve the lipid profile effectively
      and safely in NIDDM. Results from post hoc analyses of diabetic subgroups in the
      large intervention trials suggest that some statins significantly reduce the risk
      for IHD-related mortality/morbidity. However, because these results are derived
      from secondary prevention trials, we cannot be sure if these benefits apply to
      all diabetic subjects or only to those who already have IHD. Nevertheless, it
      seems logical to assume that this benefit also applies to NIDDM patients who do
      not have IHD because they share a similar vascular risk as nondiabetic subjects
      who have IHD. Intervention trials using statins and fibrates, alone or in
      combination, in NIDDM are under way. In a few years these trials will provide
      definitive end-point-based evidence in this high-risk group of patients.

PMID- 11457676
TI  - Evaluation and treatment of syncope in infants.
AB  - Syncope in the infant and newborn occurs as a loss of consciousness due to a
      variety of etiologies. Because syncope at this age may be a harbinger of sudden
      infant death, the symptom provokes anxiety and challenges clinicians to identify
      those babies with an increased risk for life threatening events. Recently
      introduced diagnostic tests and advances in molecular biology offer promising
      potential, but the population at risk remains unknown. Controversy surrounds:
      many potential risk factors; the value of home monitoring; and appropriate
      preventive and therapeutic strategies. This article reviews the differential
      diagnosis of syncope in children less than 18 months of age, with particular
      attention to those diagnoses and problems specific to the evaluation and
      treatment in this age group. Recommendations are presented for an efficient
      evaluation, which must include a careful history, complete physical examination
      and thorough investigation of the family history and home environment. In
      addition, specific diagnostic tests and a practical approach to treatment are
      suggested.

PMID- 11457677
TI  - Evaluation of syncope in adult congenital heart disease.
AB  - Approximately one million adults in the United States have congenital heart
      disease. The practitioner who sees one of these patients presenting with syncope
      must have a thorough understanding of: the underlying disease process; the
      associated congenital heart abnormalities; the type of surgery performed; the
      potential surgical residua; and the natural and unnatural history of this type of
      heart disease. Several types of congenital heart disease including: atrial septal
      defects; ventricular septal defects; left-sided obstructive lesions; Ebstein
      Anomaly; tetralogy of Fallot; and transposition of the great arteries are
      reviewed.

PMID- 11457678
TI  - Evaluation of the athlete who 'goes to ground'
AB  - The athlete represents the healthiest segment of our society. Yet, there are
      still reports of sudden death occurring while on the athletic field. Any athlete
      who 'goes to ground' temporarily (syncope) warrants an immediate investigation.
      The differential diagnosis of syncope is wide-ranging. However, if a cardiac
      cause is the underlying etiology of an athlete with syncope, and that athlete
      participates and has another syncopal episode the likelihood of resuscitation may
      be quite low. This article reviews the most common causes of sudden death in
      athletes (hypertrophic cardiomyopathy, anomalous coronary arteries,
      arrhythmogenic right ventricular cardiomyopathy, myocarditis, and dilated
      cardiomyopathy). Important attention will be centered on the pathophysiology of
      each abnormality and how it contributes to symptoms of syncope and sudden death.
      Also, the ideal evaluation of each will be reviewed. Recommendations regarding
      eligibility for competition in sports with each underlying abnormality will be
      reviewed. In addition, this article will review the evaluation of children and
      young adults who wish to participate in athletics.

PMID- 11457679
TI  - Evaluation and treatment of pediatric patients with congenital or acquired long
      QT interval syndromes.
AB  - The long QT syndrome should be considered when evaluating patients with syncope.
      Prolongation of the QT interval and abnormalities of T wave morphology due to
      abnormal ventricular repolarization characterize the syndrome. In the past
      decade, molecular genetics has revealed that abnormal repolarization is the
      result of gene mutations encoding integral ion channels that generate the cardiac
      action potential. Eight subgroups of long QT syndrome associated with five genes
      have been described to date. The explosion in research in this area has led to a
      greater understanding of the clinical expression of autosomal dominant (Romano
      Ward syndrome), autosomal recessive (Jervell and Lange-Nielsen syndrome) and
      acquired forms of the disease. This has also led to investigation in the area of
      genotype-specific therapy. The purpose of this review is to outline the strides
      made in the field of molecular genetics and update the reader on the recent
      advances in diagnosis and treatment of the long QT syndrome.

PMID- 11457680
TI  - Evaluation and treatment of other arrhythmic causes of syncope in children and
      adolescents with an apparently normal heart: Wolff-Parkinson-White syndrome and
      right ventricular cardiomyopathy.
AB  - Syncope could be a symptom of tachyarrhythmias related to the Wolff-Parkinson
      White syndrome, or the consequence of the ventricular tachycardias seen in
      patients with Arrhythmogenic Right Ventricular Cardiomyopathy. Syncope should be
      considered the consequence of atrial fibrillation or flutter, with rapid
      conduction over the accessory atrioventricular connection in Wolff-Parkinson
      White syndrome, and these patients are at risk of presenting with ventricular
      fibrillation and sudden death. Radiofrequency ablation of the anomalous,
      accessory connection, which can be performed with high success and low
      complication rates, should be the first line of treatment for symptomatic
      children and adolescents with Wolff-Parkinson-White. Arrhythmogenic Right
      Ventricular Cardiomyopathy is a rare disorder of the cardiac muscle affecting
      predominantly, although not exclusively, the right ventricle. Clinical
      presentation varies from asymptomatic cases to patients with severe symptoms
      related to life-threatening arrhythmias, right ventricular failure, or congestive
      heart failure with involvement of both ventricles. The clinical diagnosis is
      difficult. A set of major and minor criteria has been proposed to help to
      identify patients with this disease. Without an identified cause, the treatment
      of patients with Arrhythmogenic Right Ventricular Cardiomyopathy is symptomatic.
      Medical management of the associated congestive heart failure, pharmacologic
      treatment of the arrhythmias, radiofrequency ablation and implantable
      cardioverter-defibrillator therapy should all be considered.

PMID- 11457681
TI  - Evaluation and treatment of pediatric patients with neurocardiogenic syncope.
AB  - Neurocardiogenic syncope is the most common form of syncope in children. The most
      widely accepted mechanism of its etiology is a vigorous contraction of the heart
      due to relative hypovolemia leading to stimulation of C-fibers and sympathetic
      withdrawal. Episodes usually occur with an upright position and are preceded by a
      typical prodrome. A classic history is paramount to the diagnosis. Tilt testing
      aids in the diagnosis in certain cases. The cornerstone of therapy is maintaining
      adequate hydration and avoiding situations that may lead to harm with syncopal
      events. Beta blockers, fludrocortisone, alpha adrenergic agents and disopyramide
      are commonly used to prevent syncope. Seratonin reuptake inhibitors, pacing with
      rate drop algorithms and tilt training are relatively new in the armamentarium of
      therapy.

PMID- 11457682
TI  - Pediatric neurologist as consultant in evaluation of syncope in infants and
      children: when to refer.
AB  - The features and incidence of syncope in pediatric patients are different from
      those in adults. While serious medical problems may underlie the problem in
      children and adolescents, they tend to be less frequent, both in absolute numbers
      and in percentages of involved patients. This article introduces a less rigid
      classification compared to more classical classifications. It is the author's
      hope that this classification system may help define the individual in need of
      further, more detailed neurological evaluation and possible consultation. The
      importance of the history and examination in this evaluation will be emphasized.

PMID- 11457683
TI  - Costs and utility of tests in the evaluation of the pediatric patients with
      syncope.
AB  - New diagnostic tests have markedly improved the ability to establish a cause of
      syncope in pediatric patients, but at a substantial cost. The goal of syncope
      evaluation should be to diagnose treatable causes and identify patients at high
      risk for sudden death. The diagnostic utility of commonly used tests is reviewed.
      Although there are limited data on the application of specific diagnostic tests
      in the child with syncope, most tests have a low yield in unselected patients. A
      more directed approach to testing, based on the results of history, physical
      examination and the electrocardiogram is likely to result in significant cost
      reduction while still identifying patients with life threatening disorders.
      Validation of such an approach awaits prospective evaluation.

PMID- 11457684
TI  - Anatomy and pathophysiology of facial aging.
AB  - The major forces responsible for facial aging include gravity, soft tissue
      maturation, skeletal remodeling, muscular facial activity, and solar changes.
      This article discusses the anatomy and pathophysiology of facial aging by
      defining the affects of the aging process on the skeletal structure, skin, and
      musculature. How these changes affect the upper, mid, and lower thirds of the
      aging face is then examined.

PMID- 11457685
TI  - Topical and systemic therapies for the aging face.
AB  - Many cosmeseuticals and drugs are available to treat and augment therapy for the
      aging face. Patients frequently have misconceptions about the use of these
      agents, and it is important that today's cosmetic surgeon know how to maximize
      the benefits while minimizing side effects. The role of retinoids, antioxidants,
      hydroxy acids, bleaching agents, moisturizers, and sunscreens are reviewed as
      they relate to skin rejuvenation.

PMID- 11457686
TI  - Botulinum toxin (botox) chemodenervation for facial rejuvenation.
AB  - A positive attitude toward life at any age is now seen to be consistent with
      inclusion in all societal activities. A mere increase in years is no longer
      enough reason for "ageism." Botulinum Toxin (Botox) aesthetic treatments, because
      of their outstanding effectiveness and safety, can continue to play a positive
      role in the rebuttal of "ageism."

PMID- 11457687
TI  - Collagen substances.
AB  - Soft tissue enhancement has become increasingly important as more patients seek
      aesthetic improvement without major surgical procedures. Injectable Zyderm bovine
      collagen has come to be regarded as the "gold standard" of injectable or
      implantable fillers, against which all other fillers are measured. This article
      describes the techniques of injection for bovine collagen and discusses the
      indications, allergenicity, and adverse responses. Other types of available
      collagen substances are also discussed.

PMID- 11457688
TI  - Synthetic soft tissue substitutes: 2001.
AB  - The human face ages in a predictable fashion. Well-described changes in the lip
      and perioral region include progressive deepening of the nasolabial folds and
      atrophy of the lips. Conventional face lifting and endoscopic and resurfacing
      techniques do not adequately address many of these changes. As such, soft tissue
      filler materials are often used. This article outlines the history of soft tissue
      augmentation and discusses the risks and benefits of current synthetic materials.

PMID- 11457689
TI  - Fat transfer to the face: technique and new concepts.
AB  - The minimally invasive technique of using autologous fat transplantation has
      become a standard procedure in facial rejuvenation. It is simple, in-expensive,
      permanent, and effective. This article describes the technique and new concepts
      of fat transfer to the face.

PMID- 11457690
TI  - Chemical peels.
AB  - For many decades, chemical peeling has played an important role in facial
      rejuvenation. These procedures are safe and effective in the management of
      photoaging, scarring, pigmentary dyschromias, and in the destruction of
      superficial skin lesions. Chemical peels are classified into superficial, medium,
      and deep according to their level of injury to the skin. It is the responsibility
      of the surgeon to assist the patient in choosing the resurfacing procedure that
      will most effectively satisfy his or her goals while maintaining a high margin of
      safety. With the current availability of various microdermabrasion and laser
      systems for facial rejuvenation, chemical peeling continues to be an integral
      part of a facial rejuvenation program because of its popularity with patients and
      minimal costs to the physician.

PMID- 11457691
TI  - Microdermabrasion.
AB  - Particle-beam resurfacing is a tool that is useful in the management of epidermal
      abnormalities of the skin, including fine lines and wrinkles, actinic damage,
      clogged pores, comedonal acne, and mild acne scarring. For the procedure to be
      economically viable for the physician, it should be incorporated into a skin
      treatment program that can be managed safely and effectively by an appropriately
      trained nurse, aesthetician, or physician's assistant. This technique should be
      used to treat only the epidermis, because aluminum hydroxide crystals can be
      deposited into the dermis if the stratum basale is violated.

PMID- 11457692
TI  - Dermabrasion.
AB  - Dermabrasion is a time-tested and cost-effective resurfacing technique for scars,
      wrinkles, and photodamage with a track record of moderate efficacy and well-known
      safety profile. The risk of bloodborne pathogens to the operator is far greater
      with dermabrasion than other resurfacing techniques. The learning curve is
      significantly longer with dermabrasion than laser resurfacing or chemical peels.
      In expert hands, dermabrasion can achieve results comparable with laser
      resurfacing. When performed by an infrequent user of the procedure, however, the
      results achieved can be expected to be far less predictable than laser
      resurfacing.

PMID- 11457693
TI  - CO2 laser resurfacing of the face and neck.
AB  - Laser resurfacing with the short-pulsed, high-energy CO2 laser has been used to
      treat photodamaged skin and acne scars. Efficacy and safety have been
      demonstrated with this technique since 1992. Newer treatment methods, including
      sequential or combination treatment with the Er:YAG laser have led to increased
      efficacy with a decrease in adverse sequelae. This article details the author's
      experience with CO2 laser resurfacing and promotes the use of sequential
      CO2/Er:YAG laser resurfacing.

PMID- 11457694
TI  - Skin resurfacing with the erbium:YAG laser.
AB  - The Er:YAG laser provides superficial ablation and is generally used for more
      superficial rejuvenation. Three newer systems provide for thermal-coagulative and
      ablative properties. These systems are considered as intermediate resurfacing
      lasers, providing faster healing and results that are typically in between those
      of the CO2 and standard Er:YAG lasers. The use of traditional and combination
      Er:YAG lasers is reviewed along with preoperative and postoperative
      considerations.

PMID- 11457695
TI  - Nonablative laser resurfacing.
AB  - The CoolTouch (Roseville, CA) laser combines Nd:YAG 1320 nm wavelength beam and
      thermal sensing cryogenic spray. A review and presentation of data on the
      efficacy and safety of this laser are covered in this article. Clinical results
      showed that the laser is effective with few complications if thermal control is
      achieved.

PMID- 11457696
TI  - Radiofrequency resurfacing: technique and clinical review.
AB  - Radiofrequency resurfacing has recently emerged as a new modality for treating
      facial wrinkles. This approach uses a novel method of energy-mediated, "cool"
      cellular disintegration that is distinct from the tissue effects associated with
      heat-based lasers. Early clinical findings have shown that radio-frequency
      resurfacing results in significant improvement in wrinkles and overall cosmetic
      appearance. The technique is also assocaited with rapid healing, minimal pain,
      and a low incidence of adverse events. If initial clinical experience is
      confirmed in broader use, radiofrequency resurfacing could help expand the number
      of resurfacing procedures performed and could extend treatment to new and perhaps
      younger patients.

PMID- 11457697
TI  - Laser skin resurfacing.
AB  - Laser skin resurfacing has become an important component of rejuvenation surgery.
      The two wavelengths in common use are: pulsed carbon dioxide and erbium:yttrium
      aluminum garnet. The principles and techniques of using these lasers for
      resurfacing and the practice of combining these wavelengths in sequence are
      described.

PMID- 11457698
TI  - Bipolar radiofrequency resurfacing.
AB  - Bipolar radiofrequency resurfacing is a new technology for the treatment of
      facial skin changes, including photoaging, rhytids, scars, and selected facial
      lesions. It is efficacious in the treatment of these problems and offers a
      quicker recovery than that of carbon dioxide laser resurfacing.

PMID- 11457699
TI  - Nonablative laser skin tightening.
AB  - This article introduces the reader to the concept of nonablative laser skin
      tightening with the Cool Touch (Cool Touch Corp., Roseville, CA) laser, a
      minimally invasive office based procedure. This novel laser system uses dynamic
      cooling to protect the epidermis while producing a wound healing response in the
      dermis. Subtle yet positive results have been observed with this laser with
      minimal down time for patients. The development of this technology and its
      clinical applications and investigations are discussed.

PMID- 11457700
TI  - Modified phenol chemical face peels: recognizing the role of application
      technique.
AB  - The use of phenol to achieve chemexfoliation of facial tissue, following the
      standard Baker-Gordon formula or modifications of that formula, can produce a
      range of results depending on a variety of factors. This article-based on 16 new
      cases of modified phenol peels, three human biopsy studies, and one triple-blind
      study-examines the relative roles of phenol concentration, croton oil
      concentration, and application technique in the production of the chemical peel
      result. Results of this data suggest that the application technique is more
      important than the concentration of phenol or croton oil and underscore the
      importance of standardizing the application process.

PMID- 11457701
TI  - Microdermabrasion.
AB  - Microdermabrasion is a new skin resurfacing modality rapidly gaining popularity
      among the aesthetic surgery patient population. It produces a superficial wound
      to the skin, comparable with alpha hydroxy acid treatment clinically and
      histologically. Advantages include fast results, no anesthetic requirement,
      safety, and rapid recovery time. Equipment costs and training requirements are
      modest. Microdermabrasion will likely earn an important place in the skin
      resurfacing armamentarium.

PMID- 11457702
TI  - Skin care in my practice: the "spectrum concept".
AB  - The spectrum system of skin rejuvenation has proven to be a universal method
      adaptable to virtually every skin type without exception. It is a simple, logical
      approach that is easily understood by the patient, the staff, and the physician.
      It is remarkably inexpensive, user friendly, and achieves consistently successful
      results. It is an invaluable key to the comprehensive treatment of not only the
      rejuvenative patient, but it is beneficial to patients of all age groups and
      results in a beneficial long-term doctor-patient relationship and continued
      patient satisfaction.

PMID- 11457703
TI  - Current practices in the use of botulinum toxin A in the management of facial
      lines and wrinkles.
AB  - Botulinum toxin A (BTX-A) is a potent neurotoxin produced by the bacterium
      Clostridium botulinum. There are eight antigenically distinct serotypes, and they
      share a similar structure--a light chain with an associated molecule of zinc and
      a heavy chain linked by a disulfide bond. Each serotype has a separate site of
      action within the nerve ending. Only serotype A (Botox, Allergan, Irvine, CA) is
      available for clinical use in the United States.

PMID- 11457704
TI  - Survey of future injectables.
AB  - There has been an explosion in the technology of injectable filler materials for
      soft tissue augmentation of the face in the past decade. As a result, this is an
      exciting field and has provided surgeons who treat the aging face with newer,
      minimally invasive tools and techniques to augment the soft tissues of the face.
      In general, there are four classes of materials available for soft-tissue
      augmentation: synthetic, xenogeneic, homogeneic, and autogeneic. Moreover, within
      each class, these materials can be further divided, according to their longevity,
      into permanent materials, materials that last an undefined prolonged time, and
      temporary fillers. These products allow the surgeon and the patient to make
      choices that will give the best cosmetic results.

PMID- 11457705
TI  - Acellular human dermis for facial soft tissue augmentation.
AB  - The search for safe, permanent, and natural-appearing materials for soft tissue
      augmentation is ongoing. This article discusses two autologous dermal
      preparations available in injectable forms that do not cause cyst formation and
      its associated problems.

PMID- 11457706
TI  - Current practices in endoscopic brow and temporal lifting.
AB  - This article describes new innovations in the endoscopic treatment of the ptotic
      brow and temple. Extensive release of upper midface ligamentous structures and
      wide undermining of the orbicularis oculi are maneuvers that have been added to
      the standard brow lift procedure. Suspension sutures have improved brow tail and
      cheek fat elevation. Radiofrequency instrumentation and fibrin glue have allowed
      the minimization of tissue trauma during depressor muscle lysis and brow and
      temple fixation. Brow lowering techniques also have been developed to reverse the
      effects of aggressive endoscopic and coronal brow lifting.

PMID- 11457707
TI  - Endoscopic techniques for rejuvenation of the midface.
AB  - This article intends to give insight into the modern procedures available to
      facial plastic surgeons to accomplish aesthetic improvement of the midface.
      Emphasis is placed on repositioning of the malar pad and SOOF pad, which the
      author believes provides the greatest benefit to the patient.

PMID- 11457708
TI  - Endoscopic management of facial fractures.
AB  - Endoscopic management of facial fractures has lagged behind endoscopic surgery in
      other areas of the body but is rapidly gaining credibility. With the subsequent
      development of improved instrumentation for fracture reduction and stabilization,
      it is foreseeable that wide-incision exposures of the facial skeleton will be
      reserved for only the most complicated cases.

PMID- 11457709
TI  - Minimally invasive approaches to mandibular fractures.
AB  - Excellence in mandibular fracture repair requires anatomic restoration of the
      displaced bone segments, maintenance of the reduction until bone union has been
      confirmed, and minimization of surgical stigmata. Repairs should ideally be cost
      effective, reproducible, adaptable, and expeditiously executed. Fractures of two
      subregions of the mandible, the condylar neck and the symphysis, can benefit from
      minimally invasive surgical techniques. The use of these techniques in the
      mandible is reviewed.

PMID- 11457711
TI  - The organic anion transporter family: from physiology to ontogeny and the clinic.
AB  - The organic anion transporter (OAT) family handles a wide variety of clinically
      important compounds (antibiotics, nonsteriodal anti-inflammatory drugs, etc.) and
      toxins. However, little is known about their appearance during development
      despite documented differences in the handling of anionic drugs among neonates,
      children, and adults. A similar spatiotemporal pattern of mRNA expression of the
      OATs (OAT1-4) during kidney development suggests that OAT genes may be useful in
      understanding the mechanisms of proximal tubule maturation. Moreover, OAT
      expression in unexpected extrarenal sites (e.g., spinal cord, bone, skin) has
      also been detected during development, possibly indicating a role for these
      transporters in the formation or preservation of extrarenal tissues. The cloning
      of these transporters also paves the way for computer-based modeling of drug
      transporter interactions at the molecular level, potentially aiding in the design
      and assessment of new drugs. Additionally, increased understanding of single
      nucleotide polymorphisms in OATs and other transporters may eventually allow the
      use of a patient's expression profile and polymorphisms to individualize drug
      therapy.

PMID- 11457712
TI  - Effect of dietary K intake on apical small-conductance K channel in CCD: role of
      protein tyrosine kinase.
AB  - We have used Western blot to examine the expression of cSrc protein tyrosine
      kinase (PTK) and protein tyrosine phosphatase (PTP)-1D in the renal cortex, and
      the patch-clamp technique to determine the role of PTK in mediating the effect of
      dietary K intake on the small-conductance K (SK) channel in the cortical
      collecting duct (CCD). When rats were on a K-deficient (KD) diet for 1, 3, 5, and
      7 days, the expression of cSrc increased by 40, 90, 140, and 135%, respectively.
      In contrast, the expression of cSrc in the renal cortex from rats on a high-K
      (HK) diet for 1, 2, and 3 days decreased by 40, 60, and 75%, respectively.
      However, the protein level of PTP-1D was not significantly changed by dietary K
      intake. The addition of 1 microM herbimycin A increased NP(o), a product of
      channel number (N) and open probability (P(o)) in the CCD from rats on a normal
      diet or on a KD diet. The increase in NP(o) was 0.30 (normal), 0.45 (1-day KD),
      0.65 (3-day KD), 1.55 (5-day KD), and 1.85 (7-day KD), respectively. Treatment of
      the CCD with herbimycin A from rats on a KD diet increased NP(o) per patch from
      the control value (0.7) to 1.4 (1-day KD), 1.6 (3-day KD), 2.6 (5-day KD), and
      3.5 (7-day KD), respectively. In contrast, HK intake for as short as 1 day
      abolished the effect of herbimycin A. Furthermore, the expression of ROMK
      channels in the renal cortex was the same between rats on a KD diet or on a HK
      diet. Moreover, treatment with herbimycin A did not further increase NP(o) in the
      CCDs from rats on a HK diet. We conclude that dietary K intake plays a key role
      in regulating the activity of the SK channels and that PTK is involved in
      mediating the effect of the K intake on channel activity in the CCD.

PMID- 11457713
TI  - Cell surface expression and turnover of the alpha-subunit of the epithelial
      sodium channel.
AB  - The renal epithelial cell line A6, derived from Xenopus laevis, expresses
      epithelial Na(+) channels (ENaCs) and serves as a model system to study hormonal
      regulation and turnover of ENaCs. Our previous studies suggest that the alpha
      subunit of Xenopus ENaC (alpha-xENaC) is detectable as 150- and 180-kDa
      polypeptides, putative immature and mature alpha-subunit heterodimers. The 150-
      and 180-kDa alpha-xENaC were present in distinct fractions after sedimentation of
      A6 cell lysate through a sucrose density gradient. Two anti-alpha-xENaC
      antibodies directed against distinct domains demonstrated that only 180-kDa alpha
      xENaC was expressed at the apical cell surface. The half-life of cell surface
      expressed alpha-xENaC was 24-30 h, suggesting that once ENaC matures and is
      expressed at the plasma membrane, its turnover is similar to that reported for
      mature cystic fibrosis transmembrane conductance regulator. No significant
      changes in apical surface expression of alpha-xENaC were observed after treatment
      of A6 cells with aldosterone for 24 h, despite a 5.3-fold increase in short
      circuit current. This lack of change in surface expression is consistent with
      previous observations in A6 cells and suggests that aldosterone regulates ENaC
      gating and increases channel open probability.

PMID- 11457714
TI  - A numerical model of acid-base transport in rat distal tubule.
AB  - The purpose of this study is to develop a numerical model that simulates acid
      base transport in rat distal tubule. We have previously reported a model that
      deals with transport of Na(+), K(+), Cl(-), and water in this nephron segment
      (Chang H and Fujita T. Am J Physiol Renal Physiol 276: F931-F951, 1999). In this
      study, we extend our previous model by incorporating buffer systems, new cell
      types, and new transport mechanisms. Specifically, the model incorporates
      bicarbonate, ammonium, and phosphate buffer systems; has cell types corresponding
      to intercalated cells; and includes the Na/H exchanger, H-ATPase, and anion
      exchanger. Incorporation of buffer systems has required the following
      modifications of model equations: new model equations are introduced to represent
      chemical equilibria of buffer partners [e.g., pH = pK(a) + log(10)
      (NH(3)/NH(4))], and the formulation of mass conservation is extended to take into
      account interconversion of buffer partners. Furthermore, finite rates of
      H(2)CO(3)-CO(2) interconversion (i.e., H(2)CO(3) &rlharr; CO(2) + H(2)O) are
      taken into account in modeling the bicarbonate buffer system. Owing to this
      treatment, the model can simulate the development of disequilibrium pH in the
      distal tubular fluid. For each new transporter, a state diagram has been
      constructed to simulate its transport kinetics. With appropriate assignment of
      maximal transport rates for individual transporters, the model predictions are in
      agreement with free-flow micropuncture experiments in terms of HCO reabsorption
      rate in the normal state as well as under the high bicarbonate load. Although the
      model cannot simulate all of the microperfusion experiments, especially those
      that showed a flow-dependent increase in HCO reabsorption, the model is
      consistent with those microperfusion experiments that showed HCO reabsorption
      rates similar to those in the free-flow micropuncture experiments. We conclude
      that it is possible to develop a numerical model of the rat distal tubule that
      simulates acid-base transport, as well as basic solute and water transport, on
      the basis of tubular geometry, physical principles, and transporter kinetics.
      Such a model would provide a useful means of integrating detailed kinetic
      properties of transporters and predicting macroscopic transport characteristics
      of this nephron segment under physiological and pathophysiological settings.

PMID- 11457715
TI  - Regulation of ANP clearance receptors by EGF in mesangial cells from NOD mice.
AB  - Mesangial cells from nonobese diabetic (NOD) mice (D-NOD) that develop diabetes
      at 2-4 mo express an increased density of atrial natriuretic peptide (ANP)
      clearance receptors [natriuretic peptide C receptor (NPR-C)] and produce less GMP
      in response to ANP than their nondiabetic counterparts (ND-NOD). Our purpose was
      to investigate how both phenotypic characteristics were regulated. Epidermal
      growth factor (EGF) and heparin-binding (HB)-EGF, but not platelet-derived growth
      factor or insulin-like growth factor I, inhibited (125)I-ANP binding to ND-NOD
      and D-NOD mesangial cells, particularly in the latter. NPR-C density decreased
      with no change in the apparent dissociation constant, and there was also a
      decrease in NPR-C mRNA expression. The EGF effect depended on activation of its
      receptor tyrosine kinase but not on that of protein kinase C, mitogen-activated
      protein kinases, or phosphoinositide-3 kinase. Activation of activator protein-1
      (AP-1) was necessary, as shown by the inhibitory effect of curcumin and the
      results of the gel-shift assay. The cGMP response to physiological concentrations
      of ANP was greater in EGF-treated D-NOD cells. These studies suggest that EGF
      potentiates the ANP glomerular effects in diabetes by inhibition of its
      degradation by mesangial NPR-C via a mechanism involving AP-1.

PMID- 11457716
TI  - Transport of NH(3)/NH in oocytes expressing aquaporin-1.
AB  - The aim of this study was to determine whether expressing aquaporin (AQP)-1 could
      affect transport of NH(3). Using ion-selective microelectrodes, the experiments
      were conducted on frog oocytes (cells characterized by low NH(3) permeability)
      expressing AQP1. In H(2)O-injected oocytes, exposure to NH(3)/NH (20 mM, pH 7.5)
      caused a sustained cell acidification and no initial increase in pH(i) (as
      expected from NH(3) influx), and the cell depolarized to near 0 mV. The absence
      of Na(+), the presence of Ba(2+), or raising bath pH (pH(B)) did not inhibit the
      magnitude of the pH(i) decrease or result in an initial increase in pH(i) when
      NH(3)/NH was added. However, after the cell was acidified (because of NH(3)/NH),
      raising pH(B) to 8.0 caused a slow increase in pH(i) but had no effect on
      membrane potential. The changes in pH(i) with raising pH(B) did not occur in the
      absence of NH(3)/NH. In AQP1 oocytes, exposure to NH(3)/NH usually resulted in
      little or no change in pH(i), and in the absence of Na(+) there was a small
      increase in pH(i) (the cell still depolarized to near 0 mV). However, after
      exposure to NH(3)/NH, raising pH(B) to 8.0 caused pH(i) to increase more than two
      times faster than in control oocytes. This increase in pH(i) is likely the result
      of increased NH(3) entry and not the result of NH transport. These results
      indicate that 1) the oocyte membrane, although highly permeable to NH, has a
      significant NH(3) permeability and 2) NH(3) permeability is enhanced by AQP1.

PMID- 11457717
TI  - Norepinephrine-induced calcium signaling pathways in afferent arterioles of
      genetically hypertensive rats.
AB  - This study provides new information about the relative importance of calcium
      mobilization and entry in the renal vascular response to adrenoceptor activation
      in afferent arterioles isolated from 7- to 8-wk-old Wistar-Kyoto (WKY) and
      spontaneously hypertensive rats (SHR). Intracellular free calcium concentration
      ([Ca(2+)](i)) was measured in microdissected arterioles utilizing ratiometric
      photometry of fura 2 fluorescence. There was no significant strain difference in
      baseline [Ca(2+)](i). Norepinephrine (NE; 10(-6) and 10(-7) M) elicited
      immediate, sustained increases in [Ca(2+)](i). The general temporal pattern of
      response to 10(-6) M NE consisted of an initial peak and a maintained plateau
      phase. The response to NE was partially blocked by nifedipine (10(-6) M) or 8
      (N,N-diethylamino) octyl-3,4,5-trimetoxybenzoate (TMB-8; 10(-5) M). A calcium
      free external solution abolished the sustained [Ca(2+)](i) plateau response to
      NE, with less influence on the peak response. In the absence of calcium entry,
      TMB-8 (10(-5) M) completely blocked the calcium response to NE in WKY but not
      SHR, suggesting strain differences in mobilization. A higher concentration of TMB
      8 (10(-4) M), however, blocked all discernible mobilization in both strains. We
      conclude that there are differences in Ca(2+) handling in renal resistance
      vessels between young WKY and SHR with respect to mobilization stimulated by
      alpha-adrenoceptors. Afferent arterioles of young SHR appear to have a larger
      inositol-1,4,5-trisphosphate-sensitive pool or release from a site less
      accessible to TMB-8.

PMID- 11457718
TI  - Independent organic cation transport activity of Na(+)-L-carnitine cotransport
      system in LLC-PK(1) cells.
AB  - We investigated expression of the Na(+)-L-carnitine cotransport system and its
      role in transport of tetraethylammonium in a kidney epithelial cell line, LLC
      PK(1). L-Carnitine uptake in the LLC-PK(1) cells was markedly stimulated in the
      presence of Na(+). The uptake was saturable, with Michaelis constant and maximal
      uptake velocity values of 7.8 microM and 153.7 pmol x mg protein(-1) x 15 min(
      1), respectively. Cationic drugs such as tetraethylammonium, cimetidine, and
      quinidine inhibited L-carnitine uptake. The basolateral-to-apical transport of
      [(14)C]tetraethylammonium was enhanced markedly in the presence of an H(+)
      gradient on the apical side at a pH of 5.9. Under the conditions in which Na(+)/L
      carnitine cotransport activity was saturable by the addition of 100 microM L
      carnitine to the apical-side medium, the basolateral-to-apical transcellular
      transport of [(14)C]tetraethylammonium was unaffected. These results suggested
      that the Na(+)-L-carnitine cotransporter is expressed in the apical membranes of
      LLC-PK(1) cells, and is not responsible for efflux of tetraethylammonium from the
      cells. Transport of tetraethylammonium appeared to be mediated predominantly by
      an H(+)/organic cation antiporter in the apical membranes.

PMID- 11457719
TI  - K(+)-induced HSP-72 expression is mediated via rapid Ca(2+) influx in renal
      epithelial cells.
AB  - Pathophysiological stimuli, including hypoxia, lead to K(+) efflux from the
      intracellular lumen to the extracellular space, thereby increasing local tissue
      K(+) concentrations and depolarizing resident cells. In this study, we
      investigated the effects of increased extracellular K(+) concentrations
      ([K(+)](e)) on heat shock protein (HSP) expression in the porcine proximal tubule
      epithelial cell line LLC-PK(1). We analyzed HSP-25, HSP-72, HSC-73, and HSP-90
      protein expression by Western blot analyses and HSP-72 promoter activity by
      luciferase reporter gene assays using the proximal 1,440 bp of the HSP-72
      promoter. Elevating [K(+)](e) from 20 to 50 mM increased HSP-72 protein
      expression and promoter activity but did not affect HSP-25, HSC-73, or HSP-90
      levels. Addition of identical concentrations of sodium chloride did not increase
      HSP-72 expression to a similar amount. The Ca(2+) channel blocker diltiazem and
      the Ca(2+)-specific chelator EGTA-AM abolished high [K(+)](e)-induced HSP-72
      expression by 69.7 and 75.2%, respectively, indicating that the transcriptional
      induction of HSP-72 involves Ca(2+) influx. As measured by confocal microscopy
      using the Ca(2+) dye fluo 3-AM, we also observed a rapid increase of
      intracellular Ca(2+) concentration as early as 30 s after placing LLC-PK(1) cells
      in high [K(+)](e). We further analyzed whether Ca(2+) influx was necessary for
      induction of HSP-72 expression by high [K(+)](e) using Ca(2+)-free medium. Here,
      induction of HSP-72 in response to high [K(+)](e) was completely abolished. Our
      data thus demonstrate activation of a protective cellular response to ionic
      stress, e.g., elevated K(+) concentrations, by specifically increasing protein
      levels of HSP-72.

PMID- 11457720
TI  - Essential role of NHE3 in facilitating formate-dependent NaCl absorption in the
      proximal tubule.
AB  - The absorption of NaCl in the proximal tubule is markedly stimulated by formate.
      This stimulation of NaCl transport is consistent with a cell model involving Cl(
      )-formate exchange in parallel with pH-coupled formate recycling due to nonionic
      diffusion of formic acid or H(+)-formate cotransport. The formate recycling
      process requires H(+) secretion. Although Na(+)-H(+) exchanger isoform NHE3
      accounts for the largest component of H(+) secretion in the proximal tubule, 40
      50% of the rates of HCO absorption or cellular H(+) extrusion persist in NHE3
      null mice. The purpose of the present investigation is to use NHE3 null mice to
      directly test the role of apical membrane NHE3 in mediating NaCl absorption
      stimulated by formate. We demonstrate that formate stimulates NaCl absorption in
      the mouse proximal tubule microperfused in vivo, but the component of NaCl
      absorption stimulated by formate is absent in NHE3 null mice. In contrast,
      stimulation of NaCl absorption by oxalate is preserved in NHE3 null mice,
      indicating that oxalate-stimulated NaCl absorption is independent of Na(+)-H(+)
      exchange. The virtually complete dependence of formate-induced NaCl absorption on
      NHE3 activity raises the possibility that NHE3 and the formate transporters are
      functionally coupled in the brush border membrane.

PMID- 11457721
TI  - Inducible nitric oxide synthase and glomerular hemodynamics in rats with liver
      cirrhosis.
AB  - This study was designed to test the hypothesis that glomerular de novo expression
      of inducible nitric oxide synthase (iNOS) contributes to renal hemodynamic
      abnormalities in liver cirrhosis developed 3 wk after common bile duct ligature
      (CBDL). De novo expression of iNOS mRNA was detected by RT-PCR in RNA extracts
      from isolated CBDL rat glomeruli whereas no iNOS mRNA was found in control rat
      glomerular RNA. Immunohistochemical staining for iNOS was negative in control
      animals whereas, in CBDL rats, positive iNOS staining was detected in an
      apparently mesangial pattern in all glomeruli. Western blots of protein extracts
      from isolated glomeruli of CBDL rats, but not control animals, showed a prominent
      iNOS band of 130 kDa. Mean arterial pressure (MAP), renal plasma flow (RPF; p
      aminohippurate clearance), and glomerular filtration rate (GFR; inulin clearance)
      were unaltered in CBDL rats, but the application of 4 mg/kg L-N(6)-(1
      iminoethyl)lysine, a specific inhibitor of iNOS, reduced GFR and RPF
      significantly in CBDL rats, whereas control animals were not affected. Similar
      results were obtained with lipopolysaccharide (LPS)-pretreated animals, which
      were studied as a positive control for iNOS expression and as a model for recent
      iNOS induction. We conclude that de novo expression of iNOS occurs in glomeruli
      of rats with liver cirrhosis and that nitric oxide, generated by iNOS,
      contributes to the maintenance of glomerular filtration in the early state of
      this disease.

PMID- 11457722
TI  - Angiotensin II AT(2) receptors inhibit growth responses in proximal tubule cells.
AB  - Angiotensin II (ANG II) subtype 2 (AT(2)) receptors are expressed in the adult
      kidney, but the effects of AT(2) receptor activation are unclear. The proximal
      tubule cell line LLC-PK(1) was transfected with a plasmid containing cDNA for the
      rat AT(2) receptor. In transfected cells, specific binding of (125)I-labeled ANG
      II was detected (dissociation constant = 0.81 nM), with inhibition by the AT(2)
      antagonist PD-123319, and no effect of the AT(1) antagonist losartan. ANG II (10(
      7) M) significantly inhibited mitogen-activated protein kinase (MAPK) activity in
      transfected cells, associated with decreased phosphorylation of the extracellular
      signal-related kinases ERK1 and ERK2. ANG II stimulated phosphotyrosine
      phosphatase activity within 5 min, an effect blocked by PD-123319 and the
      phosphatase inhibitor vanadate. In transfected cells, ANG II inhibited epidermal
      growth factor-stimulated [(3)H]thymidine incorporation, an effect reversed by
      vanadate. In contrast, vanadate did not block ANG II-stimulated apoptosis of
      transfected cells. In summary, AT(2) receptors in proximal tubule cells inhibit
      MAPK activity and stimulate phosphotyrosine phosphatase. AT(2) receptor-induced
      inhibition of mitogenesis is mediated by phosphatase activation, whereas effects
      on apoptosis are insensitive to phosphatase inhibition. The data suggest that
      AT(2) receptors inhibit cell growth via distinct signaling pathways in the
      proximal tubule.

PMID- 11457723
TI  - Upregulated expression of human membrane type-5 matrix metalloproteinase in
      kidneys from diabetic patients.
AB  - Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade
      the extracellular matrix (ECM). The membrane-type matrix metalloproteinases (MT
      MMPs) are a new family of MMPs that differ from other MMPs in that they have a
      transmembrane domain that anchors them to the cell surface. MT-MMPs have been
      shown to function as receptors and activators for other MMPs and to localize
      extracellular matrix proteolysis at the pericellular region. Here we report on
      mRNA and protein expression of the fifth human MT-MMP (MT5-MMP), a 64-kDa protein
      that is capable of converting pro-MMP-2 to its active form, in human kidney as
      well as its upregulation in diabetes. We also demonstrate upregulation of the
      active form of MMP-2 in kidney samples from patients with diabetes. Through
      immunohistochemistry, MT5-MMP expression was localized to the epithelial cells of
      the proximal and distal tubules, the collecting duct, and the loop of Henle.
      Furthermore, the tubular epithelial cells that expressed MT5-MMP were associated
      with tubular atrophy. Because renal tubular atrophy is a significant factor in
      the pathogenesis of diabetic nephropathy and renal failure and the molecular
      mechanisms regulating this process remain unknown, it is hypothesized that the
      elevated expression of MT5-MMP contributes to the activation of pro-MMP-2, which
      participates in the remodeling of the proximal and distal tubules as well as in
      the collecting duct. These results provide the first evidence of the expression
      of a MT-MMP in diabetes and suggest a novel role for MT5-MMP in the pathogenesis
      of renal tubular atrophy and end-stage renal disease.

PMID- 11457724
TI  - Immunohistochemical localization of colonic H-K-ATPase to the apical membrane of
      connecting tubule cells.
AB  - Previous studies indicate that the colonic H-K-ATPase mRNA is expressed as the
      distal nephron. However, the exact intrarenal localization of the colonic H-K
      ATPase protein is still unclear. The goal of the present study was to determine
      the cellular and subcellular localization of the colonic H-K-ATPase protein in
      the rabbit kidney. We used three monoclonal antibodies (MAbs) directed against
      different epitopes of the rabbit colonic H-K-ATPase alpha-subunit (HKalpha(2)) to
      localize HKalpha(2) protein by immunofluorescence labeling of kidney sections and
      laser-scanning confocal microscopy. The specificity of the MAbs was confirmed by
      reaction with a single ~100-kDa band on Western blots of distal colon. Specific
      immunohistochemical reaction with the apical membrane of surface epithelial cells
      was observed with all three MAbs on distal colon sections. In rabbit kidney,
      immunofluorescence was detected only on the apical membrane of connecting tubule
      cells. Immunofluorescence was not detected in the cortical-, outer-, and inner
      medullary collecting ducts. Furthermore, costaining with principal- and
      intercalated cell-specific MAbs and a MAb against the thick ascending limb
      suggests that these cell types express HKalpha(2) protein at levels that are
      below the detection limit with this method. We conclude that in the rabbit
      kidney, under normal dietary conditions, the HKalpha(2) protein is expressed in
      the apical membrane of connecting tubule cells.

PMID- 11457725
TI  - Specific association of nitric oxide synthase-2 with Rac isoforms in activated
      murine macrophages.
AB  - Nitric oxide synthase-2 (NOS2) is responsible for high-output nitric oxide
      production important in renal inflammation and injury. Using a yeast two-hybrid
      assay, we identified Rac2, a Rho GTPase member, as a NOS2-interacting protein.
      NOS2 and Rac2 proteins coimmunoprecipitated from activated RAW 264.7 macrophages.
      The two proteins colocalized in an intracellular compartment of these cells.
      Glutathione-S-transferase (GST) pull-down assays revealed that both Rac1 and Rac2
      associated with GST-NOS2 and that the NOS2 oxygenase domain was necessary and
      sufficient for the interaction. [(35)S]methionine-labeled NOS2 interacted
      directly with GST-Rac2 in the absence of GTP, calmodulin, or NOS2 substrates or
      cofactors. Stable overexpression of Rac2 in RAW 264.7 cells augmented LPS-induced
      nitrite generation (~60%) and NOS2 activity (~45%) without measurably affecting
      NOS2 protein abundance and led to a redistribution of NOS2 to a high-speed Triton
      X-100-insoluble fraction. We conclude that Rac1 and Rac2 physically interact with
      NOS2 in activated macrophages and that the interaction with Rac2 correlates with
      a posttranslational stimulation of NOS2 activity and likely its spatial
      redistribution within the cell.

PMID- 11457726
TI  - Role of megalin in renal handling of aminoglycosides.
AB  - The role of megalin in tissue distribution of aminoglycosides was examined in
      normal rats and maleate-treated rats that shed megalin from the renal brush
      border membrane. In normal rats, amikacin administered intravenously accumulated
      most abundantly in the renal cortex, followed by the renal medulla. No amikacin
      was detected in other tissues. Tissue distributions of amikacin were well
      correlated with megalin levels in each tissue. Bolus administration of gentamicin
      increased urinary excretion of megalin ligands (vitamin D binding protein and
      calcium), suggesting the competition between gentamicin and these megalin ligands
      in renal tubules. Ligand blotting showed that binding of (45)Ca(2+) to megalin
      was inhibited by aminoglycosides. Both megalin levels and amikacin accumulation
      in renal cortex were decreased by maleate injection. Then, amikacin accumulation
      recovered proportionate to megalin levels. These findings suggest that megalin is
      involved in the renal cortical accumulation of aminoglycosides in vivo. In
      addition, the interaction between aminoglycosides and calcium in the kidney may
      be due to the competition among these compounds to bind to megalin.

PMID- 11457727
TI  - Embryonic origin and lineage of juxtaglomerular cells.
AB  - To define the embryonic origin and lineage of the juxtaglomerular (JG) cell,
      transplantation of embryonic kidneys between genetically marked and wild-type
      mice; labeling studies for renin, smooth muscle, and endothelial cells at
      different developmental stages; and single cell RT-PCR for renin and other cell
      identity markers in prevascular kidneys were performed. From embryonic kidney day
      12 to day 15 (E12 to E15), renin cells did not yet express smooth muscle or
      endothelial markers. At E16 renin cells acquired smooth muscle but not
      endothelial markers, indicating that these cells are not related to the
      endothelial lineage, and that the smooth muscle phenotype is a later event in the
      differentiation of the JG cell. Prevascular genetically labeled E12 mouse kidneys
      transplanted into the anterior chamber of the eye or under the kidney capsule of
      adult mice demonstrated that renin cell progenitors originating within the
      metanephric blastema differentiated in situ to JG cells. We conclude that JG
      cells originate from the metanephric mesenchyme rather than from an extrarenal
      source. We propose that renin cells are less differentiated than (and have the
      capability to give rise to) smooth muscle cells of the renal arterioles.

PMID- 11457728
TI  - Immunohistochemical localization of H-K-ATPase alpha(2c)-subunit in rabbit
      kidney.
AB  - The rabbit kidney possesses mRNA for the H-K-ATPase alpha(1)-subunit (HKalpha(1))
      and two splice variants of the H-K-ATPase alpha(2)-subunit (HKalpha(2)). The
      purpose of this study was to determine the specific distribution of one of these,
      the H-K-ATPase alpha(2c)-subunit isoform (HKalpha(2c)), in rabbit kidney by
      immunohistochemistry. Chicken polyclonal antibodies against a peptide based on
      the NH(2) terminus of HKalpha(2c) were used to detect HKalpha(2c)
      immunoreactivity in tissue sections. Immunohistochemical localization of
      HKalpha(2c) revealed intense apical immunoreactivity in a subpopulation of cells
      in the connecting segment, cortical collecting duct, and outer medullary
      collecting duct in both the outer and inner stripe. An additional population of
      cells exhibited a thin apical band of immunolabel. Immunohistochemical
      colocalization of HKalpha(2c) with carbonic anhydrase II, the Cl(-)/HCO exchanger
      AE1, and HKalpha(1) indicated that both type A and type B intercalated cells
      possessed intense apical HKalpha(2c) immunoreactivity, whereas principal cells
      and connecting segment cells had only a thin apical band of HKalpha(2c). Labeled
      cells were evident through the middle third of the inner medullary collecting
      duct in the majority of animals. Immunolabel was also present in papillary
      surface epithelial cells, cells in the cortical thick ascending limb of Henle's
      loop (cTAL), and the macula densa. Thus in the rabbit kidney, apical HKalpha(2c)
      is present and may contribute to acid secretion or potassium uptake throughout
      the connecting segment and collecting duct in both type A and type B intercalated
      cells, principal cells, and connecting segment cells, as well as in cells in
      papillary surface epithelium, cTAL, and macula densa.

PMID- 11457729
TI  - Increased CO(2) stimulates K/Rb reabsorption mediated by H-K-ATPase in CCD of
      potassium-restricted rabbit.
AB  - Apical H-K-ATPase in the cortical collecting duct (CCD) plays an important role
      in urinary acidification and K reabsorption. Our previous studies demonstrated
      that an H-K-ATPase mediates, in part, Rb reabsorption in rabbit CCD (Zhou X and
      Wingo CS. Am J Physiol Renal Fluid Electrolyte Physiol 263: F1134-F1141, 1992).
      The purpose of these experiments was to examine using in vitro microperfused CCD
      from K-restricted rabbits 1) whether an acute increase in PCO(2) and, presumably,
      intracellular acidosis stimulate K absorptive flux; and 2) whether this
      stimulation was dependent on the presence of a functional H-K-ATPase. Rb
      reabsorption was significantly increased after exposure to 10% CO(2) in CCD, and
      this effect was persistent for the entire 10% CO(2) period, whereas 10 microM SCH
      28080 in the perfusate totally abolished the stimulation of Rb reabsorption by
      10% CO(2). After stimulation of Rb reabsorption by 10% CO(2), subsequent addition
      of 0.1 mM methazolamide, an inhibitor of carbonic anhydrase, failed to affect Rb
      reabsorption. However, simultaneous exposure to 10% CO(2) and methazolamide
      prevented the stimulation of Rb reabsorption. Treatment with the intracellular
      calcium chelator MAPTAM (0.5 microM) inhibited the stimulation of Rb reabsorption
      by 10% CO(2). Similar inhibition was also observed in the presence of either a
      calmodulin inhibitor, W-7 (0.5 microM), or colchicine (0.5 mM), an inhibitor of
      tubulin polymerization. In time control studies, the perfusion time did not
      significantly affect Rb reabsorption. We conclude the following: 1) stimulation
      of Rb reabsorption on exposure to 10% CO(2) is dependent on the presence of a
      functional H-K-ATPase and appears to be regulated in part by the insertion of
      this enzyme into the apical plasma membrane by exocytosis; 2) insertion of H-K
      ATPase requires changes in intracellular pH and needs a basal level of
      intracellular calcium concentration; and 3) H-K-ATPase insertion occurs by a
      microtubule-dependent process.

PMID- 11457730
TI  - Ezrin binding domain-deficient NHERF attenuates cAMP-mediated inhibition of
      Na(+)/H(+) exchange in OK cells.
AB  - Na(+)/H(+) exchanger regulatory factor (NHERF), an essential protein cofactor in
      cAMP-mediated inhibition of Na(+)/H(+) exchange transporter 3 (NHE3), facilitates
      the formation of a signal complex of proteins that includes NHE3, NHERF, and
      ezrin. This model for NHE3 regulation was developed in fibroblasts and its
      applicability to epithelial cells remains to be established. Opossum kidney (OK)
      cells were transfected with either empty vector (control), full-length mouse (m)
      NHERF(1-355), or a truncated mNHERF(1-325) that lacked ezrin binding and had been
      demonstrated in fibroblasts to bind NHE3 but not mediate its cAMP-associated
      inhibition. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) at 10(-4) M
      inhibited Na(+)/H(+) exchange activity in control and OK cells expressing wild
      type mNHERF(1-355) by >60% but by <10% in cells expressing mNHERF(1-325). NHE3
      coimmunoprecipitated with mNHERF(1-325), but cAMP phosphorylation of NHE3 was
      impaired in cells expressing mNHERF(1-325). The inhibitory effect of
      hyperosmolality on NHE3 activity and the uptake of 3-O-methyl-D-glucose was the
      same in all three cell lines. Cell surface expression of NHE3 was not changed by
      cAMP in any of the cells lines. These data indicate that disruption of the NHERF
      ezrin signal complex attenuates the inhibitory effect of cAMP on NHE3 activity in
      OK cells and provides evidence supporting the proposed model of protein kinase A
      regulation of NHE3 in epithelial cells.

PMID- 11457731
TI  - p53 family update: p73 and p63 develop their own identities.

PMID- 11457732
TI  - Expression of Ca(2+)/calmodulin-dependent protein kinase IV (caMKIV) messenger
      RNA during murine embryogenesis.
AB  - Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is a monomeric,
      multifunctional serine/threonine protein kinase that is expressed in subanatomic
      regions of the central and peripheral nervous system, T lymphocytes, and male
      germ cells. It is frequently localized to the nucleus, where it serves as a
      mediator of Ca(2+)-dependent gene expression. Although CaMKIV expression in the
      adult rat central nervous system and thymus has been described, little is known
      about the embryonic expression of murine CaMKIV. Here we report a thorough
      embryonic expression study of CaMKIV mRNA from embryonic day 9.5 through
      postnatal day 1. Expression patterns during embryonic development are
      significantly different from those of adults, suggesting specific roles for
      CaMKIV during development. Regions of high CaMKIV mRNA expression include thymic
      and bone cartilage primordia as well as specific cranial nerve ganglia
      (trigeminal, vestibulocochlear, and glossopharyngeal), thalamus, and dorsal root
      ganglia. This pattern of expression is chronologically consistent with periods of
      extensive cellular differentiation, proliferation, or neuronal survival selection
      and shows a predilection for neural crest-derived cells. These trends, along with
      recent studies in the CaMKIV null mouse, suggest that CaMKIV may play an
      important physiological role in cellular differentiation during embryogenesis.

PMID- 11457733
TI  - Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible
      factor 1.
AB  - The phosphatidylinositol 3-kinase (PI3K) signaling pathway has inherent oncogenic
      potential. It is up-regulated in diverse human cancers by either a gain of
      function in PI3K itself or in its downstream target Akt or by a loss of function
      in the negative regulator PTEN. However, the complete consequences of this up
      regulation are not known. Here we show that insulin and epidermal growth factor
      or an inactivating mutation in the tumor suppressor PTEN specifically increase
      the protein levels of hypoxia-inducible factor (HIF) 1alpha but not of HIF-1beta
      in human cancer cell lines. This specific elevation of HIF-1alpha protein
      expression requires PI3K signaling. In the prostate carcinoma-derived cell lines
      PC-3 and DU145, insulin- and epidermal growth factor-induced expression of HIF
      1alpha was inhibited by the PI3K-specific inhibitors LY294002 and wortmannin in a
      dose-dependent manner. HIF-1beta expression was not affected by these inhibitors.
      Introduction of wild-type PTEN into the PTEN-negative PC-3 cell line specifically
      inhibited the expression of HIF-1alpha but not that of HIF-1beta. In contrast to
      the HIF-1alpha protein, the level of HIF-1alpha mRNA was not significantly
      affected by PI3K signaling. Vascular endothelial growth factor reporter gene
      activity was induced by insulin in PC-3 cells and was inhibited by the PI3K
      inhibitor LY294002 and by the coexpression of a HIF-1 dominant negative
      construct. Vascular endothelial growth factor reporter gene activity was also
      inhibited by expression of a dominant negative PI3K construct and by the tumor
      suppressor PTEN.

PMID- 11457734
TI  - PTEN/MMAC1 overexpression decreases insulin-like growth factor-I-mediated
      protection from apoptosis in neuroblastoma cells.
AB  - Insulin-like growth factor I (IGF-I) protects cells from apoptosis primarily
      through the action of phosphatidylinositol-3 kinase and the downstream
      serine/threonine kinase Akt. The PTEN gene product, a protein which
      dephosphorylates phosphatidylinositol lipids, prevents activation of Akt and
      regulates several cellular functions, including cell cycle progression, cell
      migration, and survival from apoptosis. In this study, PTEN overexpression
      decreases IGF-I-induced Akt activity, enhances serum withdrawal-induced
      apoptosis, and decreases IGF-I protection and cell growth in SHEP cells. The PTEN
      lipid phosphatase mutant G129E fails to inhibit IGF-I-stimulated Akt activity and
      protection from apoptosis. The C124S mutation, which abolishes both lipid and
      protein phosphatase activity, fails to inhibit Akt activity and IGF-I protection
      against hyperosmotic-induced apoptosis but still inhibits growth and IGF-I
      protection against serum withdrawal-induced apoptosis. These data suggest a role
      for PTEN in modulating the effect of IGF-I on Akt activity, neuroblastoma cell
      growth, and protection against apoptotic stimuli.

PMID- 11457735
TI  - Src family tyrosine kinases participate in insulin-like growth factor I mitogenic
      signaling in 3T3-L1 cells.
AB  - Insulin-like growth factor-I (IGF-I) stimulates proliferation and differentiation
      of many cell types, including preadipocytes. We have previously shown that IGF-I
      stimulates proliferation of 3T3-L1 preadipocytes through activation of the
      extracellular regulated kinase (ERK)-1 and -2 mitogen-activated protein kinase
      (MAPK) pathway, and that IGF-I-stimulated MAPK is predominantly downstream of
      Shc, not IRS-1 phosphorylation. The Src family of nonreceptor tyrosine kinases
      has been shown to mediate the mitogenic effects of other growth factors that also
      activate Shc and the ERK-1 and -2 MAPKs. Although Src family kinases (SFK) have
      been implicated in IGF-I action, no specific role for SFKs in IGF-I regulation of
      mitogenesis has been previously demonstrated. We studied the role of SFKs in IGF
      I mitogenic signaling in 3T3-L1 preadipocytes. The SFK-selective inhibitor PP1
      completely inhibited both IGF-I-stimulated DNA synthesis and MAPK activation in
      proliferating 3T3-L1 cells. PP1 inhibited IGF-I phosphorylation of Shc but not of
      IRS-1. In addition, IGF-I activation of MAPK was inhibited in proliferating cells
      transiently transfected with a dominant-negative c-Src. Finally, the kinetics of
      SFK and MAPK activation by IGF-I suggest that SFKs may act upstream of MAPK. IGF
      I activation of SFK members c-Src and Fyn occurred within 1 min of treatment, and
      activity was back to baseline by 10 min. Our previous studies found that IGF-I
      activation of MAPK peaked at 5 min and was also back to baseline by 10 min. Our
      results are the first to demonstrate that SFKs mediate IGF-I mitogenic signaling
      in 3T3-L1 cells and add to the growing body of evidence that SFKs play a crucial
      role in IGF-I action.

PMID- 11457737
TI  - Bush administration and the Democratic senate wrestle with health care.

PMID- 11457738
TI  - AT(2), judgment day: which angiotensin receptor is the culprit in cardiac
      hypertrophy?

PMID- 11457739
TI  - Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a
      longitudinal study by high-resolution, noninvasive magnetic resonance imaging.
AB  - BACKGROUND: This study was designed to investigate the effects of lipid-lowering
      by simvastatin on human atherosclerotic lesions. METHODS AND RESULTS: Eighteen
      asymptomatic hypercholesterolemic patients with documented aortic and/or carotid
      atherosclerotic plaques were selected for the study. A total of 35 aortic and 25
      carotid artery plaques were detected. Serial black-blood MRI of the aorta and
      carotid artery of the patients was performed at baseline and 6 and 12 months
      after lipid-lowering therapy with simvastatin. The effects of the treatment on
      atherosclerotic lesions were measured as changes in lumen area, vessel wall
      thickness, and vessel wall area, a surrogate of atherosclerotic burden.
      Simvastatin induced a significant (P<0.01) reduction in total and LDL cholesterol
      levels at 6 weeks that was maintained thereafter. At 6 months, no changes in
      lumen area, vessel wall thickness, or vessel wall area were observed. However, at
      12 months, significant reductions in vessel wall thickness and vessel wall area,
      without changes in lumen area, were observed in both aortic and carotid arteries
      (P<0.001). CONCLUSIONS: This in vivo human study demonstrates that effective and
      maintained lipid-lowering therapy by simvastatin is associated with a significant
      regression of atherosclerotic lesions. Our observation suggests that statins
      induce vascular remodeling, as manifested by reduced atherosclerotic burden
      without changes in the lumen.

PMID- 11457740
TI  - Apoptosis of endothelial cells precedes myocyte cell apoptosis in
      ischemia/reperfusion injury.
AB  - BACKGROUND: Apoptosis contributes to cell loss after ischemia/reperfusion injury
      in the heart. This study describes the time course and level of apoptosis in
      different cell types in the intact heart during ischemia/reperfusion injury.
      METHODS AND RESULTS: Isolated Langendorff-perfused rat hearts were subjected to
      perfusion alone (control) or to 35 minutes of regional ischemia, either alone or
      followed by 5, 60, or 120 minutes of reperfusion. Sections were stained by
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and
      propidium iodide and with anti-von Willebrand factor, anti-desmin, or anti-active
      caspase 3 antibodies; they were then visualized by confocal microscopy. Sections
      were also examined by electron microscopy. No TUNEL-positive cells were seen in
      control hearts or hearts exposed to ischemia alone. Early in reperfusion, TUNEL
      staining was colocalized with endothelial cells from small coronary vessels.
      Endothelial apoptosis peaked at 1 hour of reperfusion and, at this time, there
      was clear perivascular localization of apoptotic cardiac myocytes, whose number
      was inversely proportional to their distance from a positive vessel. After 2
      hours of reperfusion, apoptotic cardiac myocytes assumed a more homogeneous
      distribution. Active caspase 3 labeling was seen independent of DNA fragmentation
      during ischemia alone, but it colocalized with TUNEL staining over the 3 time
      points of reperfusion. Immunocytochemical findings were confirmed by electron
      microscopy and Western blotting. CONCLUSIONS: In the very early stages of
      reperfusion, apoptosis is first seen in the endothelial cells from small coronary
      vessels. The radial spread of apoptosis to surrounding cardiac myocytes suggests
      that reperfusion induces the release of soluble pro-apoptotic mediators from
      endothelial cells that promote myocyte apoptosis.

PMID- 11457741
TI  - Use of human immunodeficiency virus-1 protease inhibitors is associated with
      atherogenic lipoprotein changes and endothelial dysfunction.
AB  - BACKGROUND: Human immunodeficiency virus protease inhibitors (HIV PIs) are
      associated with hyperlipidemia, hyperglycemia, and obesity; however, it is not
      known whether they increase risk of atherosclerotic vascular disease. The
      purposes of this study were to characterize the lipoprotein abnormalities
      associated with use of HIV PIs in individuals with HIV infection and to determine
      the pathophysiological significance of these changes by assessing their effect on
      endothelial dysfunction. METHODS AND RESULTS: This was a cross-sectional study of
      37 adults with HIV-1 infection who were receiving antiretroviral therapy. Twenty
      two were taking HIV PIs (group 1); 15 were not (group 2). Lipids and lipoproteins
      were measured by enzymatic techniques and nuclear magnetic resonance
      spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery
      was measured by high-resolution ultrasound. Subjects in both groups were similar
      in regard to age, time since diagnosis of HIV infection, and CD4 cell count.
      Group 1 subjects had higher total cholesterol (5.68 versus 4.42 mmol/L, P=0.007)
      and triglyceride (4.43 versus 1.98 mmol/L, P=0.009) levels, characterized by
      elevated levels of IDL and VLDL. Subjects in group 1 had impaired FMD (2.6+/
      4.6%), indicative of significant endothelial dysfunction. Group 2 subjects had
      normal FMD (8.1+/-6.7%, P=0.005). In group 1, chylomicron, VLDL, IDL, and HDL
      cholesterol levels predicted FMD. CONCLUSIONS: Use of HIV PIs is associated with
      atherogenic lipoprotein changes and endothelial dysfunction. Because these
      metabolic and vascular changes predispose to atherosclerosis, monitoring and
      treatment of dyslipidemia in patients taking these medications is warranted.

PMID- 11457742
TI  - Simple bedside additive tool for prediction of in-hospital mortality after
      percutaneous coronary interventions.
AB  - BACKGROUND: Risk-adjustment models for percutaneous coronary intervention (PCI)
      mortality have been recently reported, but application in bedside prediction of
      prognosis for individual patients remains untested. METHODS AND RESULTS: Between
      July 1, 1997 and September 30, 1999, 10 796 consecutive procedures were performed
      in a consortium of 8 hospitals. Predictors of in-hospital mortality were
      identified by use of multivariate logistic regression analysis. The final model
      was validated by use of the bootstrap technique. Additional validation was
      performed on an independent data set of 5863 consecutive procedures performed
      between October 1, 1999, and August 30, 2000. An additive risk-prediction score
      was developed by rounding coefficients of the logistic regression model to the
      closest half-integer, and a visual bedside tool for the prediction of individual
      patient prognosis was developed. In this patient population, the in-hospital
      mortality rate was 1.6%. Multivariate regression analysis identified acute
      myocardial infarction, cardiogenic shock, history of cardiac arrest, renal
      insufficiency, low ejection fraction, peripheral vascular disease, lesion
      characteristics, female sex, and advanced age as independent predictors of death.
      The model had excellent discrimination (area under the receiver operating
      characteristic curve, 0.90) and was accurate for prediction of mortality among
      different subgroups. Near-perfect correlation existed between calculated scores
      and observed mortality, with higher scores associated with higher mortality.
      CONCLUSIONS: Accurate predictions of individual patient risk of mortality
      associated with PCI can be achieved with a simple bedside tool. These predictions
      could be used during discussions of prognosis before and after PCI.

PMID- 11457743
TI  - Stroke in relation to cardiac procedures in patients with non-ST-elevation acute
      coronary syndrome: a study involving >18 000 patients.
AB  - BACKGROUND: There are few published data on risk factors for stroke in patients
      with non-ST-elevation acute coronary syndrome (ACS). We investigated prognostic
      factors for stroke in 2 large cohorts of patients from the Organization to Assess
      Strategies for Ischemic Syndromes (OASIS) registry (8010) and the OASIS-2 trial
      (10 141). METHODS AND RESULTS: A total of 18 151 patients with non-ST-elevation
      ACS were enrolled in the OASIS program. Data from these 2 studies were pooled (a
      test for heterogeneity was nonsignificant, P=0.34). Overall, 238 patients (1.3%)
      had a stroke over a 6-month follow-up. Those who experienced stroke had a 4-fold
      increase in 6-month mortality (27.0% versus 6.3%, P<0.001). A Cox multivariate
      regression analysis identified CABG surgery as the most important predictor of
      stroke (hazard ratio [HR], 4.6), followed by history of stroke (HR, 2.3),
      diabetes mellitus (HR, 1.7), older age (HR, 1.6 per 10-year increase), higher
      heart rate (HR, 1.1 per 10-bpm increase), and on-site catheterization facility
      (HR, 1.4). There was no significant excess in stroke in patients undergoing
      percutaneous coronary intervention (P=0.21). Patients who underwent early CABG
      surgery were at a substantially increased risk compared with those who had later
      CABG (3.3% versus 1.6%; HR, 2.1; P=0.003) or who had no surgery (3.3% versus
      1.1%; HR, 3.95; P=0.0001). CONCLUSIONS: In this large cohort of patients with
      ACS, stroke was an uncommon but serious event associated with high mortality. The
      performance of early CABG surgery was a powerful independent predictor of stroke.

PMID- 11457744
TI  - Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3)
      and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated
      cardiomyopathy: implications for cardiotropic viral infections.
AB  - BACKGROUND: The coxsackievirus and adenovirus receptor (CAR) was identified as a
      common cellular receptor for both viruses, but its biological and pathogenic
      relevance is uncertain. Knowledge of CAR localization in the human cardiovascular
      system is limited but important with respect to CAR-dependent viral infections
      and gene transfer using CAR-dependent viral vectors. METHODS AND RESULTS:
      Explanted failing hearts from 13 patients (8 with dilated cardiomyopathy [DCM]
      and 5 with other heart diseases [non-DCM]) and normal donor hearts (n=7) were
      investigated for the expression levels and subcellular localization of CAR and
      the adenovirus coreceptors alpha(v)beta(3) and alpha(v)beta(5) integrins. CAR
      immunoreactivity was very low in normal and non-DCM hearts, whereas strong CAR
      signals occurred at the intercalated discs and sarcolemma in 5 of the 8 DCM
      hearts (62.5%); these strong signals colocalized with both integrins. In all
      hearts, CAR was detectable in subendothelial layers of the vessel wall, but not
      on the luminal endothelial surface, and on interstitial cells. Human CAR (hCAR)
      expressed in rat cardiomyocytes was targeted to cell-cell contacts, which
      resembled CAR localization in DCM hearts and resulted in 15-fold increased
      adenovirus uptake. CONCLUSIONS: Low hCAR abundance may render normal human
      myocardium resistant to CAR-dependent viruses, whereas re-expression of hCAR,
      such as that observed in DCM, may be a key determinant of cardiac susceptibility
      to viral infections. Asymmetric expression of hCAR in the vessel wall may be an
      important determinant of adenovirus tropism in humans. hCAR subcellular
      localization in human myocardium and hCAR targeting to cell-cell contacts in
      cardiomyocyte cultures suggest that hCAR may play a role in cell-cell contact
      formation.

PMID- 11457745
TI  - Effects of candesartan on cough and bronchial hyperresponsiveness in mildly to
      moderately hypertensive patients with symptomatic asthma.
AB  - BACKGROUND: Candesartan, an AT(1) receptor antagonist, has been reported to have
      no association with persistent cough in subjects with hypertension, but there has
      been no study on the safety of its administration to hypertensive patients with
      symptomatic asthma. The aim of this study was to compare the adverse effects of
      candesartan and calcium antagonists on cough, pulmonary function, and bronchial
      hyperresponsiveness in these patients. METHODS AND RESULTS: Sixty mildly to
      moderately hypertensive patients with bronchial asthma received either
      candesartan (n=30) or the calcium antagonists nifedipine or manidipine (n=30) for
      6 months. The candesartan group included 5 subjects with a history of ACE
      inhibitor-induced cough. There were no differences between the 2 groups in
      patient characteristics, ACE gene polymorphism, pulmonary function, or bronchial
      hyperresponsiveness to methacholine. Control of hypertension was the primary end
      point; new cough detected by self-administrated questionnaire and an increase in
      cough frequency by visual analog scale were the second end point. No patient
      complained of persistent cough. Neither mean visual analog scale score nor
      pulmonary functions changed during this study. Bronchial hyperresponsiveness had
      a tendency to improve in the candesartan group, but there was no difference
      between the 2 groups. CONCLUSIONS: Incidence, frequency, and severity of
      persistent cough, pulmonary functions, and bronchial hyperresponsiveness did not
      change in either the candesartan or calcium antagonist group. It is suggested
      that candesartan is as effective and safe as calcium antagonists in the treatment
      of hypertension associated with symptomatic asthma.

PMID- 11457746
TI  - Usefulness of serum carboxy-terminal propeptide of procollagen type I in
      assessment of the cardioreparative ability of antihypertensive treatment in
      hypertensive patients.
AB  - BACKGROUND: We investigated whether serum concentration of carboxy-terminal
      propeptide of procollagen type I (PIP), a marker of collagen type I synthesis,
      can be used to assess the ability of antihypertensive treatment to regress
      myocardial fibrosis in hypertensive patients. METHODS AND RESULTS: The study was
      performed in 37 patients with essential hypertension and hypertensive heart
      disease. After randomization, 21 patients were assigned to losartan and 16
      patients to amlodipine treatment. At baseline and after 12 months, right septal
      endomyocardial biopsies were performed to quantify collagen volume fraction (CVF)
      on picrosirius red-stained sections with an automated image-analysis system.
      Serum PIP was measured by specific radioimmunoassay. Nineteen patients in the
      losartan group and 11 in the amlodipine group finished the study. Time-course
      changes in blood pressure during treatment were similar in the 2 groups of
      patients. In losartan-treated patients, CVF decreased from 5.65+/-2.03% to 3.96+/
      1.46% (P<0.01) and PIP from 127+/-30 to 99+/-26 microgram/L (P<0.01). Neither CVF
      or PIP changed significantly in amlodipine-treated patients. CVF was directly
      correlated with PIP (r=0.44, P<0.001) in all hypertensives before and after
      treatment. CONCLUSIONS: These findings suggest that the ability of
      antihypertensive treatment to regress fibrosis in hypertensives with biopsy
      proven myocardial fibrosis is independent of its antihypertensive efficacy. Our
      data also suggest that blockade of the angiotensin II type 1 receptor is
      associated with inhibition of collagen type I synthesis and regression of
      myocardial fibrosis in hypertensives. Thus, determination of serum PIP may be
      useful to assess the cardioreparative properties of antihypertensive treatment in
      hypertensives.

PMID- 11457747
TI  - Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in
      patients with reduced left ventricular function: a Danish investigations of
      arrhythmia and mortality on dofetilide (diamond) substudy.
AB  - BACKGROUND: In patients with left ventricular dysfunction, atrial fibrillation
      and flutter (AF and AFl, respectively) are common arrhythmias associated with
      increased morbidity and mortality. The present study investigated the potential
      of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and
      maintain sinus rhythm, which might reduce mortality and hospitalizations. METHODS
      AND RESULTS: In the Danish Investigations of Arrhythmia and Mortality ON
      Dofetilide (DIAMOND) studies, 506 patients were in AF-AFl at baseline. Over the
      course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%)
      placebo-treated patients. In these patients, the probability of maintaining sinus
      rhythm for 1 year was 79% with dofetilide versus 42% with placebo (P<0.001).
      Dofetilide had no effect on all-cause mortality, but restoration and maintenance
      of sinus rhythm was associated with significant reduction in mortality (risk
      ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P<0.0001). In addition, dofetilide
      therapy was associated with a significantly lower risk ratio versus placebo for
      either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P</=0.005) or congestive heart
      failure (RR, 0.69; 95% CI, 0.51 to 0.93; P</=0.02) rehospitalization.
      CONCLUSIONS: Dofetilide is safe and increases the probability of obtaining and
      maintaining sinus rhythm in patients with structural heart disease. The present
      study suggests that restoration of sinus rhythm is associated with improved
      survival.

PMID- 11457748
TI  - Simultaneous noncontact mapping of left atrium in patients with paroxysmal atrial
      fibrillation.
AB  - BACKGROUND: Catheter ablation of pulmonary vein ectopic foci is a potentially
      curative treatment strategy for patients with atrial fibrillation. However,
      identification of arrhythmogenic pulmonary veins with conventional mapping is
      difficult, especially in patients with rare focal activity, multiple active foci,
      or extrapulmonary foci. The present study was designed to investigate use of
      simultaneous noncontact mapping in this setting. METHODS AND RESULTS: In 17
      consecutive patients with paroxysmal atrial fibrillation, a catheter-mounted
      noncontact multielectrode array positioned in the left atrium was used to
      reconstruct 3300 electrograms simultaneously from a single beat. Isopotential
      maps were generated during sinus rhythm and focal activity. After ectopic foci
      were identified, radiofrequency catheter ablation was performed in patients with
      1 or 2 foci. However, in patients who had multiple foci, intraoperative ablation
      of atrial fibrillation was advised. A total of 28 ectopic foci (25 pulmonary vein
      foci and 3 extrapulmonary vein foci) were identified by use of isopotential maps
      generated from a single beat of focal activity. Radiofrequency catheter ablation
      guided by noncontact mapping was attempted in 12 patients with 1 or 2 ectopic
      foci. Successful ablation of atrial fibrillation was achieved in 9 of 12 patients
      (75%). CONCLUSIONS: Noncontact mapping allows rapid and precise identification of
      arrhythmogenic pulmonary veins in addition to extrapulmonary vein foci. Thus, the
      present study shows that the technology may be used not only to guide
      radiofrequency catheter ablation, but also as a diagnostic tool to develop
      individual treatment strategies.

PMID- 11457749
TI  - Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature
      of patients with abdominal aneurysms.
AB  - BACKGROUND: Patients with abdominal aortic aneurysms (AAAs) exhibit arterial
      dilation and altered matrix composition throughout the vasculature. Matrix
      metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and
      overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a primary
      etiological event in aneurysm genesis. The aim of this study was to investigate
      MMP-2 production in vascular tissue remote from the abdominal aorta. METHODS AND
      RESULTS: Inferior mesenteric vein (IMV) was harvested from patients undergoing
      aneurysm repair (n=21) or colectomy for diverticular disease (n=13, control).
      Matrix composition of the vessels was determined by stereological techniques.
      MMPs were extracted from tissue homogenates and quantified by gelatin zymography
      and ELISA. MMP-2, membrane type-1 MMP (MT1-MMP), and tissue inhibitor of
      metalloproteinases type 2 (TIMP-2) expression were determined by Northern
      analysis. SMCs were isolated from IMV, and the production and expression of MMP-2
      and TIMP-2 in the SMC lines were quantified. Tissue homogenates and isolated
      inferior mesenteric SMCs from patients with aneurysms demonstrated significantly
      elevated MMP-2 levels, with no difference in TIMP-2 or MT1-MMP. These differences
      were a result of increased MMP-2 expression. Histological examination revealed
      fragmentation of elastin fibers within venous tissue obtained from patients with
      AAA and a significant depletion of the elastin within the media. In situ
      zymography localized elastolysis to medial SMCs. CONCLUSIONS: Patients with AAA
      have elevated MMP-2 levels in the vasculature remote from the aorta. This finding
      is due to increased MMP-2 expression from SMCs, a characteristic maintained in
      tissue culture. These data support both the systemic nature of aneurysmal disease
      and a primary role of MMP-2 in aneurysm formation.

PMID- 11457750
TI  - Reliability of multicenter pediatric echocardiographic measurements of left
      ventricular structure and function: the prospective P(2)C(2) HIV study.
AB  - BACKGROUND: To assess the reliability of pediatric echocardiographic
      measurements, we compared local measurements with those made at a central
      facility. METHODS AND RESULTS: The comparison was based on the first
      echocardiographic recording obtained on 735 children of HIV-infected mothers at
      10 clinical sites focusing on measurements of left ventricular (LV) dimension,
      wall thicknesses, and fractional shortening. The recordings were measured locally
      and then remeasured at a central facility. The highest agreement expressed as an
      intraclass correlation coefficient (ICC=0.97) was noted for LV dimension, with
      much lower agreement for posterior wall thickness (ICC=0.65), fractional
      shortening (ICC=0.64), and septal wall thickness (ICC=0.50). The mean dimension
      was 0.03 cm smaller in central measurements (95% prediction interval [PI], -0.32
      to 0.25 cm) for which 95% PI reflects the magnitude of differences between local
      and central measurements. Mean posterior wall thickness was 0.02 cm larger in
      central measurements (95% PI, -0.18 to 0.22 cm). Mean fractional shortening was
      1% smaller in central measurements. However, the 95% PI was -10% to 8%,
      indicating that a fractional shortening of 32% measured centrally could be
      anywhere between 22% and 40% when measured locally. Central measurements of mean
      septal thickness were approximately 0.1 cm thicker than local ones (95% PI, -0.18
      to 0.34 cm). Centrally measured wall thickness was more closely related to
      mortality and possibly was more valid than local measurements. CONCLUSIONS:
      Although LV dimension was reliably measured, local measurements of LV wall
      thickness and fractional shortening differed from central measurements.

PMID- 11457751
TI  - Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves
      cardiac function in a transgenic rabbit model of human hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease characterized by
      cardiac hypertrophy, myocyte disarray, interstitial fibrosis, and left
      ventricular (LV) dysfunction. We have proposed that hypertrophy and fibrosis, the
      major determinants of mortality and morbidity, are potentially reversible. We
      tested this hypothesis in beta-myosin heavy chain-Q(403) transgenic rabbits.
      METHODS AND RESULTS: We randomized 24 beta-myosin heavy chain-Q(403) rabbits to
      treatment with either a placebo or simvastatin (5 mg. kg(-1). d(-1)) for 12 weeks
      and included 12 nontransgenic controls. We performed 2D and Doppler
      echocardiography and tissue Doppler imaging before and after treatment.
      Demographic data were similar among the groups. Baseline mean LV mass and
      interventricular septal thickness in nontransgenic, placebo, and simvastatin
      groups were 3.9+/-0.7, 6.2+/-2.0, and 7.5+/-2.1 g (P<0.001) and 2.2+/-0.2, 3.1+/
      0.5, and 3.3+/-0.5 mm (P=0.002), respectively. Simvastatin reduced LV mass by
      37%, interventricular septal thickness by 21%, and posterior wall thickness by
      13%. Doppler indices of LV filling pressure were improved. Collagen volume
      fraction was reduced by 44% (P<0.001). Disarray was unchanged. Levels of
      activated extracellular signal-regulated kinase (ERK) 1/2 were increased in the
      placebo group and were less than normal in the simvastatin group. Levels of
      activated and total p38, Jun N-terminal kinase, p70S6 kinase, Ras, Rac, and RhoA
      and the membrane association of Ras, RhoA, and Rac1 were unchanged. CONCLUSIONS:
      Simvastatin induced the regression of hypertrophy and fibrosis, improved cardiac
      function, and reduced ERK1/2 activity in the beta-myosin heavy chain-Q(403)
      rabbits. These findings highlight the need for clinical trials to determine the
      effects of simvastatin on cardiac hypertrophy, fibrosis, and dysfunction in
      humans with hypertrophic cardiomyopathy and heart failure.

PMID- 11457752
TI  - JAK/STAT signaling is associated with cardiac dysfunction during ischemia and
      reperfusion.
AB  - BACKGROUND: Activation of the heart renin-angiotensin system (RAS) under
      pathophysiological conditions has been correlated with the development of
      ischemic injury. The binding of angiotensin II to its receptors triggers
      induction of several, perhaps multifunctional, intracellular signaling pathways,
      notable among them the Janus kinase/signal transducer and activator of
      transcription (JAK/STAT) pathway. In this study, we investigated whether the
      JAK/STAT signaling is involved in the ischemia/reperfusion injury in adult rat
      myocardium. METHODS AND RESULTS: We report here that 2 components of the JAK/STAT
      signaling pathway, namely STAT 5A and STAT 6, are selectively activated in the
      rat heart subjected to ischemia/reperfusion. The activated STATs bind to a
      conserved nucleotide sequence (St domain) in the promoter of the angiotensinogen
      (ANG) gene and consequently upregulate the level of ANG mRNA. Treatment of the
      hearts with losartan (4.5 micromol/L), an AT(1) blocker, or with tyrphostin AG490
      (5 micromol/L), an inhibitor of JAK 2 phosphorylation, results in loss of the
      STAT/ANG promoter binding activity and an upregulated level of ANG mRNA. Hearts
      treated with the JAK 2 inhibitor tyrphostin AG490 showed a reduction in
      myocardial infarct size and in number of cardiomyocytes undergoing apoptosis. The
      treated hearts also showed a recovery in functional hemodynamics of the
      myocardium. CONCLUSIONS: These findings suggest that activation of the JAK/STAT
      signaling pathway is a significant contributing factor to the pathogenesis of
      myocardial ischemia and that interference in activation of the pathway
      potentiates recovery in cardiac function.

PMID- 11457753
TI  - Akt activation preserves cardiac function and prevents injury after transient
      cardiac ischemia in vivo.
AB  - BACKGROUND: The serine-threonine kinase Akt is activated by several ligand
      receptor systems previously shown to be cardioprotective. Akt activation reduces
      cardiomyocyte apoptosis in models of transient ischemia. Its role in cardiac
      dysfunction or infarction, however, remains unclear. METHODS AND RESULTS: We
      examined the effects of a constitutively active Akt mutant (myr-Akt) in a rat
      model of cardiac ischemia-reperfusion injury. In vivo gene transfer of myr-Akt
      reduced infarct size by 64% and the number of apoptotic cells by 84% (P<0.005 for
      each). Ischemia-reperfusion injury decreased regional cardiac wall thickening as
      well as the maximal rate of left ventricular pressure rise and fall (+dP/dt and 
      dP/dt). Akt activation restored regional wall thickening and +dP/dt and -dP/dt to
      levels seen in sham-operated rats. To better understand this benefit, we examined
      the effects of myr-Akt on hypoxic cardiomyocyte dysfunction in vitro. myr-Akt
      prevented hypoxia-induced abnormalities in cardiomyocyte calcium transients and
      shortening. Akt activation also enhanced sarcolemmal expression of Glut-4 in vivo
      and increased glucose uptake in vitro to the level seen with insulin treatment.
      CONCLUSIONS: Akt activation exerts a powerful cardioprotective effect after
      transient ischemia that probably reflects its ability to both inhibit
      cardiomyocyte death and improve function of surviving cardiomyocytes. Akt may
      represent an important nodal target for therapy in ischemic and other heart
      disease.

PMID- 11457754
TI  - Transmural distribution of three-dimensional systolic strains in stunned
      myocardium.
AB  - BACKGROUND: Regional function in stunned myocardium is usually thought to be more
      depressed in the endocardium than the epicardium. This has been attributed to the
      greater loss of blood flow at the endocardium during ischemia. METHODS AND
      RESULTS: We measured transmural distributions of 3D systolic strains relative to
      local myofiber axes in open-chest anesthetized dogs before 15 minutes of left
      anterior descending coronary artery occlusion and during 2 hours of reperfusion.
      During ischemia, regional myocardial blood flow was reduced 84% at the
      endocardium and 32% at the epicardium (P<0.005, n=7), but changes in end-systolic
      fiber length from baseline were transmurally uniform. Relative to baseline,
      radial segments in stunned tissue were significantly thinner at the endocardium
      than the epicardium at end systole (24+/-5% versus 16+/-3%; P<0.05, n=8),
      consistent with previous reports. Unlike radial and cross-fiber segments,
      however, the increase of end-systolic fiber lengths in stunned myocardium had no
      significant transmural gradient (23+/-8% epicardium versus 21+/-4% endocardium).
      We also observed significant 3D diastolic dysfunction in the ischemic-reperfused
      region transmurally. CONCLUSIONS: Myocardial ischemia/reperfusion in the dog
      results in a significant transmural gradient of dysfunction between epicardial
      and endocardial layers in radial and cross-fiber segments, but not for fiber
      segments, despite a gradient in blood flow reduction during ischemia. Perhaps
      systolic fiber dysfunction rather than the degree of perfusion deficit during the
      preceding ischemic period may be the main determinant of myocardial dysfunction
      during reperfusion.

PMID- 11457755
TI  - Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial
      nitric oxide synthase.
AB  - BACKGROUND: Insulin resistance and arterial hypertension are related, but the
      underlying mechanism is unknown. Endothelial nitric oxide synthase (eNOS) is
      expressed in skeletal muscle, where it may govern metabolic processes, and in the
      vascular endothelium, where it regulates arterial pressure. METHODS AND RESULTS:
      To study the role of eNOS in the control of the metabolic action of insulin, we
      assessed insulin sensitivity in conscious mice with disruption of the gene
      encoding for eNOS. eNOS(-/-) mice were hypertensive and had fasting
      hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose
      uptake than control mice. Insulin resistance in eNOS(-/-) mice was related
      specifically to impaired NO synthesis, because in equally hypertensive 1-kidney/1
      clip mice (a model of renovascular hypertension), insulin-stimulated glucose
      uptake was normal. CONCLUSIONS: These results indicate that eNOS is important for
      the control not only of arterial pressure but also of glucose and lipid
      homeostasis. A single gene defect, eNOS deficiency, may represent the link
      between metabolic and cardiovascular disease.

PMID- 11457756
TI  - Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and
      cardiac fibrosis in chronic angiotensin II-induced hypertension.
AB  - BACKGROUND: The roles of angiotensin II (Ang II) in the regulation of heart
      function under normal and pathological conditions have been well documented.
      Although 2 types of Ang II receptor (AT(1) and AT(2)) are found in various
      proportions, most studies have focused on AT(1)-coupled events. In the present
      study, we examined the hypothesis that signaling by AT(2) is important to the
      development of left ventricular hypertrophy and cardiac fibrosis by Ang II
      infusion in mice lacking the AT(2) gene (Agtr2-/Y). METHODS AND RESULTS: Male
      Agtr2-/Y and age-matched wild-type (WT) mice were treated long-term with Ang II,
      infused at a rate of 4.2 ng. kg(-1). min(-1) for 3 weeks. Ang II elevated
      systolic blood pressure to comparable levels in Agtr2-/Y and WT mice. WT mice
      developed prominent concentric cardiac hypertrophy, prominent fibrosis, and
      impaired diastolic relaxation after Ang II infusion. In contrast, there was no
      cardiac hypertrophy in Agtr2-/Y mice. Agtr2-/Y mice, however, did not show signs
      of heart failure or impairment of ventricular relaxation and only negligible
      fibrosis after Ang II infusion. The absence of fibrosis may be a clue to the
      absence of impairment in ventricular relaxation and account for the normal left
      ventricular systolic and diastolic performances in Agtr2-/Y mice. CONCLUSIONS:
      Chronic loss of AT(2) by gene targeting abolished left ventricular hypertrophy
      and cardiac fibrosis in mice with Ang II-induced hypertension.

PMID- 11457757
TI  - Combined assessment of myocardial perfusion and regional left ventricular
      function by analysis of contrast-enhanced power modulation images.
AB  - BACKGROUND: Echocardiographic contrast media have been used to assess myocardial
      perfusion and to enhance endocardial definition for improved assessment of left
      ventricular (LV) function. These methodologies, however, have been qualitative or
      have required extensive offline image analysis. Power modulation is a recently
      developed imaging technique that provides selective enhancement of microbubble
      generated reflections. Our goal was to test the feasibility of using power
      modulation for combined quantitative assessment of myocardial perfusion and
      regional LV function in an animal model of acute ischemia. METHODS AND RESULTS:
      Coronary balloon occlusions were performed in 18 anesthetized pigs. Transthoracic
      power modulation images (Agilent 5500) were obtained during continuous
      intravenous infusion of the contrast agent Definity (DuPont) at baseline and
      during brief coronary occlusion and reperfusion and were analyzed with custom
      software. At each phase, myocardial perfusion was assessed by calculation, in 6
      myocardial regions of interest, of mean pixel intensity and the rate of contrast
      replenishment after high-power ultrasound impulses. LV function was assessed by
      calculation of regional fractional area change from semiautomatically detected
      endocardial borders. All ischemic episodes caused detectable and reversible
      changes in perfusion and function. Perfusion defects, validated with fluorescent
      microspheres, were visualized in real time and confirmed by a significant
      decrease in pixel intensity in the left anterior descending coronary artery
      territory after balloon inflation and reduced rate of contrast replenishment.
      Fractional area change decreased significantly in ischemic segments and was
      restored with reperfusion. CONCLUSIONS: Power modulation allows simultaneous
      online assessment of myocardial perfusion and regional LV wall motion, which may
      improve the echocardiographic diagnosis of myocardial ischemia.

PMID- 11457758
TI  - Vascular endothelial growth factor-B-deficient mice display an atrial conduction
      defect.
AB  - BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are
      essential regulators of vasculogenesis and angiogenesis in both embryos and
      adults. One of the factors with a still unknown physiological function is VEGF-B,
      which is expressed in many tissues, including the heart. METHODS AND RESULTS:
      Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/
      ) animals, no gross abnormalities were observed in organs that normally show high
      expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart
      function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction
      abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast
      growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-)
      mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult
      animals but is not required for proper development of the cardiovascular system
      either during development or for angiogenesis in adults.

PMID- 11457759
TI  - Current concepts of the pathogenesis of the acute coronary syndromes.

PMID- 11457760
TI  - Noninvasive postoperative angiography for internal mammary artery grafts.

PMID- 11457761
TI  - Aneurysm of the abdominal aorta.

PMID- 11457762
TI  - Cardiovascular news. Totally contained AbioCor artificial heart implanted July 3,
      2001.

PMID- 11457763
TI  - Invited editorial on "Myogenic satellite cells: physiology to molecular biology".

PMID- 11457764
TI  - Myogenic satellite cells: physiology to molecular biology.
AB  - Adult skeletal muscle has a remarkable ability to regenerate following myotrauma.
      Because adult myofibers are terminally differentiated, the regeneration of
      skeletal muscle is largely dependent on a small population of resident cells
      termed satellite cells. Although this population of cells was identified 40 years
      ago, little is known regarding the molecular phenotype or regulation of the
      satellite cell. The use of cell culture techniques and transgenic animal models
      has improved our understanding of this unique cell population; however, the
      capacity and potential of these cells remain ill-defined. This review will
      highlight the origin and unique markers of the satellite cell population, the
      regulation by growth factors, and the response to physiological and pathological
      stimuli. We conclude by highlighting the potential therapeutic uses of satellite
      cells and identifying future research goals for the study of satellite cell
      biology.

PMID- 11457765
TI  - Adenosine A(1) receptors mediate plasma exudation from the oral mucosa.
AB  - The purpose of this study was to pharmacologically characterize the adenosine
      receptor subtype(s) that mediates adenosine-induced increases in macromolecular
      efflux from the intact hamster cheek pouch. Using intravital microscopy, we found
      that 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (PACPX), a selective
      adenosine receptor-1 antagonist, but not 3,7-dimethyl-1-propargylxanthine (DMPX),
      a selective adenosine receptor-2 antagonist, significantly attenuated adenosine
      induced leaky site formation and increased clearance of fluorescein
      isothiocyanate-labeled dextran (molecular mass, 70 kDa) from the intact hamster
      cheek pouch (P < 0.05). Both compounds had no significant effects on bradykinin
      induced responses. Nanomolar concentrations of R(-)-N(6)-(2-phenylisopropyl)
      adenosine [R(-)-PIA], a selective adenosine A(1) agonist, evoked significant,
      concentration-dependent increases in macromolecular efflux. This response was
      significantly attenuated by PACPX but not by DMPX. In contrast, CGS-21680, a
      selective adenosine A(2) agonist, increased macromolecular efflux but only at
      micromolar concentrations. This response was significantly attenuated by DMPX but
      not by PACPX. Suffusion of nitroglycerin had no significant effects on R(-)-PIA-
      and CGS-21680-induced responses. In addition, suffusion of N(G)-nitro-L-arginine
      methyl ester, a nitric oxide synthase inhibitor, had no significant effects on
      adenosine-induced responses. Indomethacin had no significant effects on adenosine
      , R(-)-PIA-, and CGS-21680-induced increases in macromolecular efflux.
      Collectively, these data indicate that adenosine increases macromolecular efflux
      from the intact hamster cheek pouch by stimulating high-affinity adenosine A(1)
      receptors in a specific, nitric oxide- and prostaglandin-independent fashion.

PMID- 11457766
TI  - Cardiovascular responses to three simple, provocative tests of autonomic activity
      in sleeping infants.
AB  - Whereas defective cardiovascular autonomic control has been implicated in the
      sudden infant death syndrome, relatively little is known about the normal
      development of autonomic control, due to the inability to measure blood pressure
      in infants noninvasively. We studied 12 normal infants [age: 13 +/- 2 (SD) wk]
      using a noninvasive method of continuous blood pressure recording and examined
      the cardiovascular responses to 45 degrees head-up tilting, a modified cold face
      test, and a loud noise. In head-up tilting, in both slow-wave sleep and rapid eye
      movement sleep, all infants displayed a rapid biphasic heart rate response (mean
      increase of 16% and mean decrease of 21%) and blood pressure response (mean
      increase of 16% and mean decrease of 16%), with a return to pretest values within
      20 s. Both ice and noise caused a less pronounced biphasic response. In
      conclusion, at 3 mo, infants show the adult pattern of response to postural
      challenge. The short latency of the response suggests that neural inputs, apart
      from baroreceptors, are involved in the initial phase of the response.

PMID- 11457767
TI  - Selective muscle hypertrophy, changes in EMG and force, and serum hormones during
      strength training in older women.
AB  - Effects of strength training (ST) for 21 wk were examined in 10 older women (64
      +/- 3 yr). Electromyogram, maximal isometric force, one-repetition maximum
      strength, and rate of force development of the leg extensors, muscle cross
      sectional area (CSA) of the quadriceps femoris (QF) and of vastus lateralis (VL),
      medialis (VM), intermedius (VI) and rectus femoris (RF) throughout the lengths of
      3/12--12/15 (Lf) of the femur, muscle fiber proportion and areas of types I, IIa,
      and IIb of the VL were evaluated. Serum hormone concentrations of testosterone,
      growth hormone (GH), cortisol, and IGF-I were analyzed for the resting,
      preexercise, and postexercise conditions. After the 21-wk ST, maximal force
      increased by 37% (P < 0.001) and 1-RM by 29% (P < 0.001), accompanied by an
      increase (P < 0.01) in rate of force development. The integrated electromyograms
      of the vastus muscles increased (P < 0.05). The CSA of the total QF increased (P
      < 0.05) throughout the length of the femur by 5--9%. The increases were
      significant (P < 0.05) at 7/15--12/15 Lf for VL and at 3/15--8/15 Lf for VM, at
      5/15--9/15 for VI and at 9/15 (P < 0.05) for RF. The fiber areas of type I (P <
      0.05), IIa (P < 0.001), and IIb (P < 0.001) increased by 22--36%. No changes
      occurred during ST in serum basal concentrations of the hormones examined, but
      the level of testosterone correlated with the changes in the CSA of the QF (r =
      0.64, P < 0.05). An acute increase of GH (P < 0.05), remaining elevated up to 30
      min (P < 0.05) postloading, was observed only at posttraining. Both neural
      adaptations and the capacity of skeletal muscle to undergo training-induced
      hypertrophy even in older women explain the strength gains. The increases in the
      CSA of the QF occurred throughout its length but differed selectively between the
      individual muscles. The serum concentrations of hormones remained unaltered, but
      a low level of testosterone may be a limiting factor in training-induced muscle
      hypertrophy. The magnitude and time duration of the acute GH response may be
      important physiological indicators of anabolic adaptations during strength
      training even in older women.

PMID- 11457768
TI  - Neck muscle vibration disrupts steering of locomotion.
AB  - Neck muscle vibration was applied to human subjects to assess the influences of
      neck abnormal proprioceptive input on the organization and execution of gait.
      Subjects walked blindfolded to a previously seen target, located straight ahead
      at ~4 m. Vibration was applied on the right side of the neck, both during and
      before walking. The variables measured were length, duration, and velocity of
      trajectory; relative and absolute frontal errors at target; and width of walking
      support base. Vibration applied during locomotion produced an undershoot of
      target and deviation of gait trajectory toward the side opposite to vibration.
      Vibration applied before locomotion produced no effect on length of trajectory
      but slowing of velocity and nonsystematic deviation. When vibration frequency was
      increased, the amplitude of the nonsystematic deviation increased. Vibration
      applied during or before stance trials had minor effects on body sway. Vibration
      before stance had no effect on the position of mean center of foot pressure,
      whereas vibration during stance displaced it to the side opposite to the vibrated
      muscle. We suggest that vibration during locomotion reduces length and velocity
      of trajectory because of a direct action on the locomotor centers and produces
      trajectory deviation related to its effect on stance. Vibration before locomotion
      causes a major, nonsystematic deviation from the planned trajectory, possibly
      connected to a disorientation of the internal references.

PMID- 11457769
TI  - Mechanical stretch promotes alveolar epithelial type II cell differentiation.
AB  - Functional maturation of pulmonary alveolar epithelial cells is crucial for
      extrauterine survival. Mechanical distension and mesenchymal-epithelial
      interactions play important roles in this process. We hypothesized that
      mechanical stretch simulating fetal breathing movements is an important regulator
      of pulmonary epithelial cell differentiation. Using a Flexercell Strain Unit, we
      analyzed effects of stretch on primary cultures of type II cells and cocultures
      of epithelial and mesenchymal cells isolated from fetal rat lungs during late
      development. Cyclic stretch of isolated type II cells increased surfactant
      protein (SP) C mRNA expression by 150 +/- 30% over controls (P < 0.02) on
      gestational day 18 and by 130 +/- 30% on day 19 (P < 0.03). Stretch of cocultures
      with fibroblasts increased SP-C expression on days 18 and 19 by 170 +/- 40 and
      270 +/- 40%, respectively, compared with unstretched cocultures. On day 19,
      stretch of isolated type II cells increased SP-B mRNA expression by 50% (P <
      0.003). Unlike SP-C, addition of fibroblasts did not produce significant
      additional effects on SP-B mRNA levels. Under these conditions, we observed only
      modest increases in cellular immunoreactive SP-B, but secreted saturated
      phosphatidylcholine rose by 40% (P < 0.002). These results indicate that cyclic
      stretch promotes developmentally timed differentiation of fetal type II cells, as
      a direct effect on epithelial cell function and via mesenchymal-epithelial
      interactions. Expression of the SP-C gene appears to be highly responsive to
      mechanical stimulation.

PMID- 11457770
TI  - Dopamine-1 receptor stimulation attenuates the vasoconstrictive response to gut
      ischemia.
AB  - The effects of fenoldopam, a dopamine-1 (DA-1) receptor agonist, were studied in
      two groups of anesthetized dogs before and after induction of splanchnic ischemia
      by way of hemorrhage. During the first portion of the experiment, both groups
      received fenoldopam (1.5 microg x kg(-1) x min(-1)) for 45 min followed by a 45
      min washout. During the second portion, hemorrhage (10 ml/kg) was induced,
      followed by no intervention in group I (controls) and restarting of the
      fenoldopam infusion in group II. Prehemorrhage, fenoldopam increased composite
      portal blood flow by 33% (P < 0.01). After hemorrhage-induced splanchnic
      ischemia, fenoldopam restored portal vein blood flow to near baseline, maintained
      the splanchnic fraction of cardiac output, and attenuated the rise in gut mucosal
      PCO(2). DA-1 receptor stimulation increased portal blood flow and redistributed
      blood flow away from the serosal layer in favor of the mucosa during basal
      conditions and after hemorrhage, suggesting a more concentrated distribution of
      splanchnic DA-1 receptors within the mucosal layer vasculature. Fenoldopam
      maintained splanchnic blood flow during hypoperfusion and attenuated the
      splanchnic vasoconstrictive response to hemorrhage.

PMID- 11457771
TI  - Hypoxic metabolic response of the golden-mantled ground squirrel.
AB  - We examined the magnitude of the hypoxic metabolic response in golden-mantled
      ground squirrels to determine whether the shift in thermoregulatory set point
      (T(set)) and subsequent fall in body temperature (T(b)) and metabolic rate
      observed in small mammals were greater in a species that routinely experiences
      hypoxic burrows and hibernates. We measured the effects of changing ambient
      temperature (T(a); 6--29 degrees C) on metabolism (O(2) consumption and CO(2)
      production), T(b), ventilation, and heart rate in normoxia and hypoxia (7% O(2)).
      The magnitude of the hypoxia-induced falls in T(b) and metabolism of the
      squirrels was larger than that of other rodents. Metabolic rate was not simply
      suppressed but was regulated to assist the initial fall in T(b) and then acted to
      slow this fall and stabilize T(b) at a new, lower level. When T(a) was reduced
      during 7% O(2), animals were able to maintain or elevate their metabolic rates,
      suggesting that O(2) was not limiting. The slope of the relationship between
      temperature-corrected O(2) consumption and T(a) extrapolated to a T(set) in
      hypoxia equals the actual T(b). The data suggest that T(set) was proportionately
      related to T(a) in hypoxia and that there was a shift from increasing ventilation
      to increasing O(2) extraction as the primary strategy employed to meet increasing
      metabolic demands under hypoxia. The animals were neither hypothermic nor
      hypometabolic, as T(b) and metabolic rate appeared to be tightly regulated at new
      but lower levels as a result of a coordinated hypoxic metabolic response.

PMID- 11457772
TI  - Contribution of CD54 to human eosinophil and neutrophil superoxide production.
AB  - We have reported that CD54 on eosinophils is involved in eosinophil
      degranulation. However, the role of CD54 in eosinophil and neutrophil superoxide
      production is still uncertain. We assessed the effect of CD54 on eosinophils and
      neutrophils in recombinant granulocyte-macrophage colony-stimulating factor (rGM
      CSF)- or phorbol myristate acetate (PMA)-induced superoxide production through
      CD18. Anti-CD54 monoclonal antibody attenuated leukocyte aggregation and
      superoxide production of rGM-CSF- or PMA-stimulated neutrophils and PMA
      stimulated eosinophils. Anti-CD18 monoclonal antibody or theophylline attenuated
      superoxide production of eosinophils and neutrophils stimulated by either
      stimuli. Flow cytometric analysis demonstrated CD54 expression on freshly
      isolated neutrophils but not on freshly isolated eosinophils. CD54 newly
      expressed on eosinophils reached its peak expression 30 min after PMA
      stimulation. The increase in CD18 and CD54 expression on neutrophils caused by
      rGM-CSF stimulation was partially inhibited by theophylline. These data
      demonstrated that CD54 and CD18 interaction of eosinophils or neutrophils is
      involved in superoxide production and that the inhibition of superoxide
      production by theophylline may be at least partly due to the inhibition of CD54
      and CD18.

PMID- 11457773
TI  - Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic
      blockade reduces insulin sensitivity.
AB  - After short-term exposure to high altitude (HA), men appear to be less sensitive
      to insulin than at sea level (SL). We hypothesized that the same would be true in
      women, that reduced insulin sensitivity would be directly related to the rise in
      plasma epinephrine concentrations at altitude, and that the addition of alpha
      adrenergic blockade would potentiate the reduction. To test the hypotheses, 12
      women consumed a high-carbohydrate meal at SL and after 16 h at simulated 4,300-m
      elevation (HA). Subjects were studied twice at each elevation: once with prazosin
      (Prz), an alpha(1)-adrenergic antagonist, and once with placebo (Pla).
      Mathematical models were used to assess insulin resistance based on fasting
      [homeostasis model assessment of insulin resistance (HOMA-IR)] and postprandial
      [composite model insulin sensitivity index (C-ISI)] glucose and insulin
      concentrations. Relative to SL-Pla (HOMA-IR: 1.86 +/- 0.35), insulin resistance
      was greater in HA-Pla (3.00 +/- 0.45; P < 0.05), SL-Prz (3.46 +/- 0.51; P <
      0.01), and HA-Prz (2.82 +/- 0.43; P < 0.05). Insulin sensitivity was reduced in
      HA-Pla (C-ISI: 4.41 +/- 1.03; P < 0.01), SL-Prz (5.73 +/- 1.01; P < 0.05), and HA
      Prz (4.18 +/- 0.99; P < 0.01) relative to SL-Pla (8.02 +/- 0.92). Plasma
      epinephrine was significantly elevated in HA-Pla (0.57 +/- 0.08 ng/ml; P < 0.01),
      SL-Prz (0.42 +/- 0.07; P < 0.05), and HA-Prz (0.82 +/- 0.07; P < 0.01) relative
      to SL-Pla (0.28 +/- 0.04), but correlations with HOMA-IR, HOMA-beta-cell
      function, and C-ISI were weak. In women, short-term exposure to simulated HA
      reduced insulin sensitivity compared with SL. The change does not appear to be
      directly mediated by a concurrent rise in plasma epinephrine concentrations.

PMID- 11457774
TI  - Intracellular PO(2) decreases with increasing stimulation frequency in
      contracting single Xenopus muscle fibers.
AB  - There is currently some controversy regarding the manner in which skeletal muscle
      intracellular PO(2) changes with work intensity. Therefore, this study
      investigated the relationship between intracellular PO(2) and stimulation
      frequency in intact, isolated, single skeletal muscle fibers. Single, living
      muscle fibers (n = 7) were microdissected from the lumbrical muscles of Xenopus
      and injected with the oxygen-sensitive probe palladium-meso-tetra(4
      carboxyphenyl)porphine (0.5 mM). Fibers were mounted with platinum clips to a
      force transducer in a chamber, which was continuously perfused with Ringer
      solution (pH = 7.0) at a PO(2) of approximately 30 Torr. Fibers were then
      stimulated sequentially for 3 min, followed by a 3-min rest, at each of five
      contraction frequencies (0.15, 0.2, 0.25, 0.33, and 0.5 Hz), in a random order,
      using tetanic contractions. Resting intracellular PO(2) averaged 31.2 +/- 0.9
      Torr. During steady-state stimulation, intracellular PO(2) declined to 21.2 +/-
      2.3, 17.1 +/- 2.4, 15.3 +/- 1.9, 9.8 +/- 2.0, and 5.8 +/- 1.4 Torr for 0.15, 0.2,
      0.25, 0.33, and 0.5-Hz stimulation, respectively. Significant fatigue, as defined
      by a decrease in force to <50% of the initial force, occurred only at the highest
      (0.5 Hz) stimulation frequency in five of the cells and at 0.33 Hz in the other
      two. Regression analysis demonstrated that there was a significant (P < 0.0001, r
      = 0.82) negative correlation between intracellular PO(2) and contraction
      frequency in these isolated, single cells. The linear decrease in intracellular
      PO(2) with stimulation frequency, and thus energy demand, suggests that a fall in
      intracellular PO(2) correlates with increased oxygen uptake in these single
      contracting cells.

PMID- 11457775
TI  - Effects of hypergravity and anti-G suit pressure on intraregional ventilation
      distribution during VC breaths.
AB  - The effects of increased gravity in the head-to-foot direction (+G(z)) and
      pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar
      ventilation inhomogeneity were explored in 10 healthy male subjects. They
      performed vital capacity (VC) single-breath washin/washouts of SF(6) and He in
      +1, +2, or +3 G(z) in a human centrifuge, with an AGS pressurized to 0, 6, or 12
      kPa. The phase III slopes for SF(6) and He over 25-75% of the expired VC were
      used as markers of total ventilation inhomogeneity, and the (SF(6) -- He) slopes
      were used as indicators of intraregional intra-acinar inhomogeneity. SF(6) and He
      phase III slopes increased proportionally with increasing gravity, but the (SF(6)
      -- He) slopes remained unchanged. AGS pressurization did not change SF(6) or He
      slopes significantly but resulted in increased (SF(6) -- He) slope differences at
      12 kPa. In conclusion, hypergravity increases overall but not intraregional intra
      acinar inhomogeneity during VC breaths. AGS pressurization provokes increased
      intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the
      consequences of basilar pulmonary vessel engorgement in combination with
      compression of the basilar lung regions.

PMID- 11457776
TI  - Cardiac atrophy after bed rest and spaceflight.
AB  - Cardiac muscle adapts well to changes in loading conditions. For example, left
      ventricular (LV) hypertrophy may be induced physiologically (via exercise
      training) or pathologically (via hypertension or valvular heart disease). If
      hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV
      work. However, whether physical inactivity in nonathletic populations causes
      adaptive changes in LV mass or even frank atrophy is not clear. We exposed
      previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest.
      LV and right ventricular (RV) mass and end-diastolic volume were measured using
      cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five
      healthy men were also studied before and after at least 6 wk of routine daily
      activities as controls. In addition, four astronauts were exposed to the complete
      elimination of hydrostatic gradients during a spaceflight of 10 days. During bed
      rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional
      atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was
      no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1
      g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of
      bed rest associated with the decrease in LV mass, suggesting a physiological
      remodeling with respect to altered load. LV end-diastolic volume decreased by 14
      +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter.
      After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and
      RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass
      decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during
      prolonged (6 wk) horizontal bed rest and may also occur after short-term
      spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation
      to reduced myocardial load and work in real or simulated microgravity and
      demonstrates the plasticity of cardiac muscle under different loading conditions.

PMID- 11457777
TI  - Exogenous carbohydrate oxidation from drinks ingested during prolonged exercise
      in a cold environment in humans.
AB  - Six healthy male volunteers performed four rides to exhaustion on a cycle
      ergometer at approximately 80% of maximal oxygen consumption. Subjects ingested a
      bolus volume of fluid (7.14 ml/kg) immediately before exercise and additional
      fluid volumes (1.43 ml/kg) every 10 min during exercise. The fluids ingested were
      either a flavored water control or glucose-electrolyte beverages with glucose
      concentrations of 2, 6, or 12%. The beverages were labeled with [U-(13)C]glucose
      (99.2%: 0.05 g/l). Exercise capacity was not different (P = 0.13) between trials;
      median (range) exercise time was 83.52 (79.85--89.68), 103.19 (78.82--108.22),
      100.37 (80.60--124.07), and 94.76 (76.78--114.25) min in the 0, 2, 6, and 12%
      trials, respectively. The oxidation of exogenous glucose in each 15-min period
      was significantly lower in the 2% trial (P = 0.02) than in the 6 and 12% trials
      where oxidation rates were between 0.5 and 0.7 g/min. No difference in endogenous
      glucose oxidation was observed between trials (P = 0.71). These findings indicate
      that the oxidation of exogenous glucose during exercise of this intensity and
      duration in a cold environment is similar to that observed in warmer conditions.
      Thus a low oxidation of exogenous substrate is unlikely to be a factor limiting
      the effectiveness of carbohydrate-electrolyte drink ingestion on exercise
      capacity in a cold environment.

PMID- 11457778
TI  - Severity of contraction-induced injury is affected by velocity only during
      stretches of large strain.
AB  - Our purpose was to investigate the effect of velocity of stretch on contraction
      induced injury to whole skeletal muscles. Single stretches provide an effective
      method for studying factors that initiate contraction-induced injury. We tested
      the null hypothesis that the severity of injury is not dependent on the velocity
      of the stretch. From the plateau of maximum isometric contractions, extensor
      digitorum longus muscles of mice were administered single stretches in situ of 30
      -50% strain relative to muscle fiber length (L(f)) at rates of 1--16 L(f)/s. The
      magnitude of injury was represented by the isometric force deficit 1--10 min
      after the stretch. Although the null hypothesis was not supported because the
      force deficit was affected by velocity (r(2) = 0.09), the effect was relatively
      weak and was not significant except at the largest strain. Velocity had no effect
      on peak or average force or work input, factors established to have significant
      relationships with the force deficit. Velocity may play a minor role in
      contraction-induced injury, but its importance is negligible relative to that of
      strain.

PMID- 11457779
TI  - An inexpensive meter to measure differences in electrical resistance in the rat
      vagina during the ovarian cycle.
AB  - The inherent electrical resistance of the rat vaginal wall rises markedly near
      the beginning of estrus and then falls again to low levels for the remainder of
      the ovarian cycle. Accordingly, special instruments have been developed to
      measure such resistances (within seconds) on simply inserting a small probe
      fitted with a pair of recording electrodes into the vagina (i.e., the MK-10A
      impedance checker and the EC40 estrus cycle monitor). As described herein, these
      two instruments are far more convenient for monitoring individual cycles than
      more laborious methods in which vaginal smears are inspected for changes in
      numbers of cornified (C), nucleated (N), and leukocytic (L) cells. However, they
      are also expensive and their use has essentially remained uncited in the
      literature. Thus we sought to determine whether a simple, inexpensive electrical
      meter (with resistance-measuring capacity), as commonly used by professional
      electricians, would serve the same purpose. We chose a standard multifunctional
      meter (model 22-178, RadioShack) and attached leads to it fabricated from the
      internal wiring of a shielded audio cable (model 42-2387A, RadioShack), one male
      terminal of which was used as a vaginal probe. In rats from which vagina smears
      revealed cell numbers in the order of C > N > L (typical of early estrus)
      electrical resistances were high, 488 +/- 130 k Omega (18 rats). In rats from
      which vagina smears revealed all other possible cell distributions, electrical
      resistances (combined) were much lower (P < 0.05), 124 +/- 23 k Omega (32 rats).
      Thus readily accessible, inexpensive electrical meters may be useful in assessing
      the status of estrus in female rats, either to improve reproductive efficiencies
      and/or for other purposes involving experiments in which such information is
      desirable.

PMID- 11457780
TI  - Effect of contraction frequency on leg blood flow during knee extension exercise
      in humans.
AB  - Previous studies in isolated muscle preparations have shown that muscle blood
      flow becomes compromised at higher contraction frequencies. The purpose of this
      study was to examine the effect of increases in contraction frequency and muscle
      tension on mean blood flow (MBF) during voluntary exercise in humans. Nine male
      subjects [23.6 +/- 3.7 (SD) yr] performed incremental knee extension exercise to
      exhaustion in the supine position at three contraction frequencies [40, 60, and
      80 contractions/min (cpm)]. Mean blood velocity of the femoral artery was
      determined beat by beat using Doppler ultrasound. MBF was calculated by using the
      diameter of the femoral artery determined at rest using echo Doppler ultrasound.
      The work rate (WR) achieved at exhaustion was decreased (P < 0.05) as contraction
      frequency increased (40 cpm, 16.2 +/- 1.4 W; 60 cpm, 14.8 +/- 1.4 W; 80 cpm, 13.2
      +/- 1.3 W). MBF was similar across the contraction frequencies at rest and during
      the first WR stage but was higher (P < 0.05) at 40 than 80 cpm at exercise
      intensities >5 W. MBF was similar among contraction frequencies at exhaustion. In
      humans performing knee extension exercise in the supine position, muscle
      contraction frequency and/or muscle tension development may appreciably affect
      both the MBF and the amplitude of the contraction-to-contraction oscillations in
      muscle blood flow.

PMID- 11457781
TI  - Acute exercise effect on postabsorptive serum leptin.
AB  - We postulated that high circulating cortisol levels during intense exercise would
      lead to increased serum leptin concentrations. Young, lean men ate a small meal
      and then exercised on a cycle ergometer for 41 min or rested on a control day.
      Serum leptin concentration was 10% greater during exercise than in the control
      condition (P < 0.05). Directly after exercise, serum leptin dropped to
      approximately 10% less than the control level (P < 0.05) but had recovered to the
      nonexercised level after approximately 2 h of recovery. Rapid exercise effects on
      circulating leptin were related to changes in hemoconcentration rather than
      changes in leptin mass. When serum leptin was normalized to serum protein, leptin
      increased by 10% in the exercise condition compared with control by the end of
      recovery (P < 0.05). Although exercise increased serum cortisol concentration
      threefold, there was no relation between differences in cortisol and exercise vs.
      control differences in normalized leptin. The increased leptin mass after
      exercise may have been related to greater plasma glucose concentration during
      recovery after exercise compared with the control condition.

PMID- 11457782
TI  - Reduced lipoprotein lipase activity in postural skeletal muscle during aging.
AB  - Lipoprotein lipase (LPL) is a key enzyme for fatty acid and lipoprotein
      metabolism in muscle. However, the effect of aging on LPL regulation in skeletal
      muscle is unknown. We report the effect of aging on LPL regulation in the soleus
      (red oxidative postural) muscle and the tibialis anterior (white glycolytic non
      weight-bearing) muscle in 4- and 24-mo-old Fischer 344 rats and 18- and 31-mo-old
      Fischer 344 x Brown-Norway F1 (F-344 x BN F1) rats. Total and heparin-releasable
      LPL (HR-LPL) activities were decreased 38% (P < 0.01) and 52% (P < 0.05),
      respectively, in the soleus muscle of the older Fischer 344 rats. There was a 32%
      reduction (P < 0.05) of total LPL protein mass in the soleus muscle with aging.
      The results were confirmed in another strain. A decrease of total LPL activity (
      50%, P < 0.05) was also found in the soleus muscle between 18- and 31-mo-old F
      344 x BN F1 rats. LPL mRNA concentration in the soleus muscle was not different
      between ages. Total LPL protein mass was reduced by 46% (P < 0.05) in the soleus
      muscle of the 31-mo-old F-344 x BN F1 rats. In the tibialis anterior muscle,
      neither LPL activity nor mRNA concentration was affected by age in either strain.
      In conclusion, LPL regulation in a non-weight-bearing muscle was not affected by
      aging. However, there was a pronounced reduction in LPL activity and LPL protein
      mass in postural muscle with aging.

PMID- 11457783
TI  - Insight into skeletal muscle mechanotransduction: MAPK activation is
      quantitatively related to tension.
AB  - The mechanism by which mechanical forces acting through skeletal muscle cells
      generate intracellular signaling, known as mechanotransduction, and the details
      of how gene expression and cell size are regulated by this signaling are poorly
      understood. Mitogen-activated protein kinases (MAPKs) are known to be involved in
      mechanically induced signaling in various cell types, including skeletal muscle
      where MAPK activation has been reported in response to contraction and passive
      stretch. Therefore, the investigation of MAPK activation in response to
      mechanical stress in skeletal muscle may yield important information about the
      mechanotransduction process. With the use of a rat plantaris in situ preparation,
      a wide range of peak tensions was generated through passive stretch and
      concentric, isometric, and eccentric contractile protocols, and the resulting
      phosphorylation of c-Jun NH(2)-terminal kinase (JNK), extracellular regulated
      kinase (ERK), and p38 MAPKs was assessed. Isoforms of JNK and ERK MAPKs were
      found to be phosphorylated in a tension-dependent manner, such that eccentric >
      isometric > concentric > passive stretch. Peak tension was found to be a better
      predictor of MAPK phosphorylation than time-tension integral or rate of tension
      development. Differences in maximal response amplitude and sensitivity between
      JNK and ERK MAPKs suggest different roles for these two kinase families in
      mechanically induced signaling. A strong linear relationship between p54 JNK
      phosphorylation and peak tension over a 15-fold range in tension (r(2) = 0.89, n
      = 32) was observed, supporting the fact that contraction-type differences can be
      explained in terms of tension and demonstrating that MAPK activation is a
      quantitative reflection of the magnitude of mechanical stress applied to muscle.
      Thus the measurement of MAPK activation, as an assay of skeletal muscle
      mechanotransduction, may help elucidate mechanically induced hypertrophy.

PMID- 11457784
TI  - Inhibition of nitric oxide synthesis attenuates thermally induced asthma.
AB  - To determine whether the inhibition of nitric oxide (NO) synthesis attenuates
      thermally induced obstruction, we had 10 asthmatic volunteers perform isocapnic
      hyperventilation with frigid air after inhaling 1 mg of N(G)-monomethyl-L
      arginine (L-NMMA) or isotonic saline in a blinded fashion. The challenges were
      identical in all respects, and there were no differences in baseline lung
      function [1-s forced expiratory volume (FEV(1)); saline 2.8 +/- 0.3 liters, L
      NMMA 2.9 +/- 0.3 liters; P = 0.41] or prechallenge fractional concentration of
      nitric oxide in the exhaled air (FENO) [saline 23 +/- 6 parts/billion (ppb), L
      NMMA 18 +/- 4 ppb; P = 0.51]. Neither treatment had any impact on the FEV(1),
      pulse, or blood pressure. After L-NMMA, FENO fell significantly (P < 0.0001), the
      stimulus-response curves shifted to the right, and the minute ventilation
      required to reduce the FEV(1) 20% rose 53.5% over control (P = 0.02). The results
      of this study demonstrate that NO generated from the airways of asthmatic
      individuals may play an important role in the pathogenesis of thermally induced
      asthma.

PMID- 11457785
TI  - Ventilatory long-term facilitation in unanesthetized rats.
AB  - We tested the hypothesis that unanesthetized rats exhibit ventilatory long-term
      facilitation (LTF) after intermittent, but not continuous, hypoxia. Minute
      ventilation (VE) and carbon dioxide production (VCO(2)) were measured in
      unanesthetized, unrestrained male Sprague-Dawley rats via barometric
      plethysmography before, during, and after exposure to continuous or intermittent
      hypoxia. Hypoxia was either isocapnic [inspired O(2) fraction (FI(O(2))) = 0.08-
      0.09 and inspired CO(2) fraction (FI(CO(2))) = 0.04] or poikilocapnic (FI(O(2)) =
      0.11 and FI(CO(2)) = 0.00). Sixty minutes after intermittent hypoxia, VE or
      VE/VCO(2) was significantly greater than baseline in both isocapnic and
      poikilocapnic conditions. In contrast, 60 min after continuous hypoxia, VE and
      VE/VCO(2) were not significantly different from baseline values. These data
      demonstrate ventilatory LTF after intermittent hypoxia in unanesthetized rats.
      Ventilatory LTF appeared similar in its magnitude (after accounting for CO(2)
      feedback), time course, and dependence on intermittent hypoxia to phrenic LTF
      previously observed in anesthetized, vagotomized, paralyzed rats.

PMID- 11457786
TI  - Multiple firing of single muscle vasoconstrictor neurons during cardiac
      dysrhythmias in human heart failure.
AB  - Single vasoconstrictor nerve fibers in humans normally fire only once but have
      the capacity to fire as many as eight times, per cardiac interval. Our laboratory
      recently demonstrated that the mean firing frequency of individual
      vasoconstrictor fibers is more than doubled in the sympathoexcitation associated
      with congestive heart failure (Macefield VG, Rundqvist B, Sverrisdottir YB,
      Wallin BG, and Elam M. Circulation 100: 1708--1713, 1999). However, the
      propensity to fire only once per cardiac interval was retained. In the present
      retrospective study, we tested the hypothesis that vasoconstrictor fibers fire
      more than once per cardiac interval in response to transient sympathoexcitatory
      stimuli, providing one mechanism for further increase of an already augmented
      sympathetic discharge. Six patients with congestive heart failure (New York Heart
      Association functional class II--IV; left ventricular ejection range 13--37%,
      average 22%) were studied at rest and during premature ectopic heartbeats.
      Analyzed for a total of 60 premature beats, the average firing probability of 10
      vasoconstrictor fibers increased from 61 to 80% in the prolonged cardiac interval
      (i.e., reduced diastolic pressure) after premature beats. The incidence of
      multiple within-burst firing increased markedly, with two spikes being more
      common than one. Our results illustrate two different mechanisms (increases in
      firing probability and multiple within-burst firing), and indirectly indicate a
      third mechanism (recruitment of previously silent fibers), for acute
      sympathoexcitatory responses.

PMID- 11457787
TI  - Ozone absorption in the human nose during unidirectional airflow.
AB  - This study addresses the effect of gas flow rate and ozone (O(3)) concentration
      on the uptake of this air pollutant in the nose. A nasal exposure system was
      developed in which a constant flow of humidified air (V) containing a constant
      concentration of O(3) (C(inlet)) entered one nostril and then exited the other
      nostril while a subject closed the velopharyngeal aperture. Experiments were
      conducted on 10 healthy nonsmokers for whom O(3) concentration was measured at
      the inlet nostril and the outlet nostril to determine the fraction of inhaled
      O(3) that was absorbed into the nasal mucosa (Lambda(nose)). Lambda(nose)
      decreased from 0.80 +/- 0.02 to 0.33 +/- 0.02 (SE) when V was increased from 3 to
      15 l/min and C(inlet) was fixed at 0.4 ppm. Analysis of these data with a
      mathematical model indicated that O(3) uptake was limited by diffusion reaction
      through mucus, rather than by convective diffusion through the respired gas. A
      small decrease in Lambda(nose) from 0.36 +/- 0.02 to 0.32 +/- 0.01 was also
      observed when C(inlet) was increased from 0.1 to 0.4 ppm at a fixed V of 15
      l/min. This may have been due to nonlinear reaction kinetics between O(3) and
      reactive substrates in mucus or an active response by a physiological process
      such as mucus secretion or transepithelial water influx.

PMID- 11457788
TI  - Validation of equilibration and chromium reduction methods for deuterium
      measurements of fluid volumes.
AB  - Determinations of fluid volumes are of importance for correct treatment of
      patients subjected to shock and trauma. Gas isotope ratio mass spectrometry
      (GIRMS) is an advanced method for analysis of stable isotopes. These can be used
      as tracers for measurement of various fluid volumes. In the current in vitro
      study, deuterium was used to determine different volumes of water simulating a
      range of body fluid volumes from neonates to adults. A high-precision scale gave
      control weights (i.e., volumes), and two methods, equilibration (EQ) and chromium
      reduction (CR), were compared by use of a GIRMS. The coefficient of variation was
      <1% when using both EQ (0.45%) and CR (0.79%). The variability was greater at
      small volumes, and, when regression equations for the relation between measured
      and calculated volumes were used as formulas, the deviation was 0.4% using EQ and
      2.8% using CR at the volume of 1,000 ml. At larger volumes, the deviation when
      using CR approached 1%. These variations are better than previously published
      data using other methods. It was concluded that GIRMS is a suitable technique for
      fluid volume determinations in neonates as well as in adult patients, using
      deuterium as a tracer. EQ and CR methods were both regarded to give acceptable
      variabilities in this in vitro study. GIRMS may in the future increasingly be
      used clinically for accurate measurements of body fluid volumes.

PMID- 11457789
TI  - Hysteresivity of the lung and tissue strip in the normal rat: effects of
      heterogeneities.
AB  - We measured lung impedance in rats in closed chest (CC), open chest (OC), and
      isolated lungs (IL) at four transpulmonary pressures with a optimal ventilator
      waveform. Data were analyzed with an homogeneous linear or an inhomogeneous
      linear model. Both models include tissue damping and elastance and airway
      inertance. The homogeneous linear model includes airway resistance (Raw), whereas
      the inhomogeneous linear model has a continuous distribution of Raw characterized
      by the mean Raw and the standard deviation of Raw (SDR). Lung mechanics were
      compared with tissue strip mechanics at frequencies and operating stresses
      comparable to those during lung impedance measurements. The hysteresivity (eta)
      was calculated as tissue damping/elastance. We found that 1) airway and tissue
      parameters were different in the IL than in the CC and OC conditions; 2) SDR was
      lowest in the IL; and 3) eta in IL at low transpulmonary pressure was similar to
      eta in the tissue strip. We conclude that eta is primarily determined by lung
      connective tissue, and its elevated estimates from impedance data in the CC and
      OC conditions are a consequence of compartment-like heterogeneity being greater
      in CC and OC conditions than in the IL.

PMID- 11457790
TI  - Extracellular glutathione inhibits oxygen-induced permeability changes in
      alveolar epithelial monolayers.
AB  - Exposure to high fractional inspired oxygen for 24 h increases permeability of
      the alveolar epithelium, contributing to the clinical manifestations of oxygen
      toxicity. Utilizing a model of the alveolar epithelium in which isolated rat type
      II cells form polarized monolayers on polycarbonate filters [transepithelial
      resistance (R(t)) > 1 k Omega x cm(2) by day 4], we evaluated the ability of
      reduced glutathione (GSH) to ameliorate these changes. On day 4, apical fluid was
      replaced with culture medium containing 1) no additives, 2) GSH (500 microM), or
      3) GSH (500 microM) + glutathione reductase (0.5 U/ml) + nicotinamide adenine
      dinucleotide phosphate (250 microM). Monolayers were exposed (for 24 h) to room
      air (control) or 95% O(2), each containing 5% CO(2). After 24 h of hyperoxia,
      R(t) for condition 1 decreased by 45% compared with control (P < 0.001). In
      conditions 2 and 3, R(t) did not decrease significantly (P = not significant).
      Hyperoxia-induced decreases in active ion transport were observed for conditions
      1 and 2 (P < 0.05), but not for condition 3 (P = not significant). These findings
      indicate that extracellular GSH may protect the alveolar epithelium against
      hyperoxia-induced injury. Addition of glutathione reductase and nicotinamide
      adenine dinucleotide phosphate may further augment these protective effects of
      GSH.

PMID- 11457791
TI  - Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and
      potassium channels.
AB  - The anorexic agent fenfluramine considerably increases the risk of primary
      pulmonary hypertension. The mechanism of this effect is unknown. The appetite
      reducing action of fenfluramine is mediated by its interaction with the
      metabolism of serotonin [5-hydroxytryptamine (5-HT)] in the brain. We tested the
      hypothesis that the pulmonary vasoconstrictive action of fenfluramine is at least
      in part mediated by 5-HT receptor activation. In addition, we sought to determine
      whether pharmacological reduction of voltage-gated potassium (K(V)) channel
      activity would potentiate the pulmonary vascular reactivity to fenfluramine.
      Using isolated rat lungs perfused with Krebs-albumin solution, we compared the
      inhibitory effect of ritanserin, an antagonist of 5-HT(2) receptors, on
      fenfluramine- and 5-HT-induced vasoconstriction. Both 5-HT (10(-5) mol/l) and
      fenfluramine (5 x 10(-4) mol/l) caused significant increases in perfusion
      pressure. Ritanserin at a dose (10(-7) mol/l) sufficient to inhibit >80% of the
      response to 5-HT reduced the response to fenfluramine by approximately 50%. A
      higher ritanserin dose (10(-5) mol/l) completely abolished the responses to 5-HT
      but had no more inhibitory effect on the responses to fenfluramine. A
      pharmacological blockade of K(V) channels by 4-aminopyridine (3 x 10(-3) mol/l)
      markedly potentiated the pulmonary vasoconstrictor response to fenfluramine but
      was without effect on the reactivity to 5-HT. These data indicate that the
      pulmonary vasoconstrictor response to fenfluramine is partly mediated by 5-HT
      receptors. Furthermore, the pulmonary vasoconstrictor potency of fenfluramine is
      elevated when the K(V)-channel activity is low. This finding suggests that
      preexisting K(V)-channel insufficiency may predispose some patients to the
      development of pulmonary hypertension during fenfluramine treatment.

PMID- 11457792
TI  - Human breath isoprene and its relation to blood cholesterol levels: new
      measurements and modeling.
AB  - Numerous publications have described measurements of breath isoprene in humans,
      and there has been a hope that breath isoprene analyses could be a noninvasive
      diagnostic tool to assess blood cholesterol levels or cholesterol synthesis rate.
      However, significant analytic problems in breath isoprene analysis and
      variability in isoprene levels with age, exercise, diet, etc., have limited the
      usefulness of these measurements. Here, we have applied proton transfer reaction
      mass spectrometry to this problem, allowing on-line detection of breath isoprene.
      We show that breath isoprene concentration increases within a few seconds after
      exercise is started as a result of a rapid increase in heart rate and then
      reaches a lower steady state when breath rate stabilizes. Additional experiments
      demonstrated that increases in heart rate associated with standing after
      reclining or sleeping are associated with increased breath isoprene
      concentrations. An isoprene gas-exchange model was developed and shows excellent
      fit to breath isoprene levels measured during exercise. In a preliminary
      experiment, we demonstrated that atorvastatin therapy leads to a decrease in
      serum cholesterol and low-density-lipoprotein levels and a parallel decrease in
      breath isoprene levels. This work suggests that there is constant endogenous
      production of isoprene during the day and night and reaffirms the possibility
      that breath isoprene can be a noninvasive marker of cholesterologenesis if care
      is taken to measure breath isoprene under standard conditions at constant heart
      rate.

PMID- 11457793
TI  - TGF-beta(1) and prepro-ANP mRNAs are differentially regulated in exercise-induced
      cardiac hypertrophy.
AB  - The induction of transforming growth factor (TGF)-beta and prepro-atrial
      natriuretic peptide (ANP) mRNAs represent hallmark features of pathological
      cardiac hypertrophy. The present study examined whether this pattern of mRNA
      expression was conserved in a physiological model of cardiac hypertrophy. To
      address this thesis, female Sprague-Dawley rats were individually housed and
      permitted to run freely. Voluntary exercise for 3 and 6 wk resulted in
      biventricular hypertrophy and increased cytochrome c oxidase activity in the
      triceps muscle. In the hypertrophied left ventricle, the steady-state mRNA level
      of the cardiac fetal gene prepro-ANP and the extracellular matrix proteins
      preprocollagen-alpha(1) and fibronectin were similar in exercise-trained and
      sedentary rats. By contrast, an increased expression of TGF-beta(1) mRNA was
      observed, whereas TGF-beta(3) mRNA level was unchanged in the hypertrophied left
      ventricle of exercise-trained compared with sedentary rats. These data highlight
      a heterogeneity in the regulation of TGF-beta isoforms, and the increased
      expression of ventricular TGF-beta(1) mRNA in physiological cardiac hypertrophy
      may contribute to myocardial remodeling.

PMID- 11457794
TI  - Multiple rostral medullary nuclei can influence breathing in awake goats.
AB  - The purpose of this study was to determine the effect on breathing of neuronal
      dysfunction in the retrotrapezoid (RTN), facial (FN), gigantocellularis
      reticularis (RGN), or vestibular (VN) nuclei of adult awake goats. Microtubules
      were chronically implanted to induce neuronal dysfunction by microinjection of an
      excitatory amino acid (EAA) receptor antagonist or a neurotoxin. The EAA receptor
      antagonist had minimal effect on eupneic breathing, but 8--10 days after
      injection of the neurotoxin, 7 of 10 goats hypoventilated (arterial PCO(2)
      increased 3.2 +/- 0.7 Torr). Overall there were no significant (P > 0.10) effects
      of the EAA receptor antagonist on CO(2) sensitivity. However, for all nuclei, >
      or =66% of the antagonist injections altered CO(2) sensitivity by more than the
      normal 12.7 +/- 1.6% day-to-day variation. These changes were not uniform,
      inasmuch as the antagonist increased (RTN, n = 2; FN, n = 7; RGN, n = 6; VN, n =
      1) or decreased (RTN, n = 2; RGN, n = 3; VN, n = 2) CO(2) sensitivity. Ten days
      after injection of the neurotoxin into the FN (n = 3) or RGN (n = 5), CO(2)
      sensitivity was also reduced. Neuronal dysfunction also did not have a uniform
      effect on the exercise arterial PCO(2) response, and there was no correlation
      between effects on CO(2) sensitivity and the exercise hyperpnea. We conclude that
      there is a heterogeneous population of neurons in these rostral medullary nuclei
      (or adjacent tissue) that can affect breathing in the awake state, possibly
      through chemoreception or chemoreceptor-related mechanisms.

PMID- 11457795
TI  - Simulated microgravity upregulates an endothelial vasoconstrictor prostaglandin.
AB  - Endothelial nitric oxide contributes to the vascular hyporesponsiveness to
      norepinephrine (NE) observed in carotid arteries from rats exposed to simulated
      microgravity. The goal of the present study was to determine whether a
      cyclooxygenase product of arachidonic acid also influences vascular
      responsiveness in this setting. Microgravity was simulated in rats by hindlimb
      unweighting (HU). After 20 days of HU, carotid arteries were isolated from
      control and HU-treated rats, and vascular rings were mounted in tissue baths for
      the measurement of isometric contraction. Two cyclooxygenase inhibitors,
      indomethacin and ibuprofen, and the selective thromboxane A(2) prostanoid
      receptor antagonist, SQ-29548, had no effect on the contraction to NE in control
      vessels but markedly reduced contraction to NE in HU vessels. When the
      endothelium was removed, indomethacin no longer had any effect on the NE-induced
      contraction in HU vessels. In endothelium-intact vessels in the presence of
      indomethacin, the addition of the nitric oxide synthase inhibitor, N(G)-L-nitro
      arginine methyl ester, to the medium bathing HU vessels increased the contraction
      to NE to the level of that of the control vessels. These results indicate that HU
      treatment induced two endothelial changes in carotid artery that opposed each
      other. Nitric oxide activity was increased and was responsible for the vascular
      hyporesponsiveness to NE. The activity of a vasoconstrictor prostaglandin was
      also increased, and attenuated the vasodilating effect of nitric oxide.

PMID- 11457796
TI  - Liquid transport properties of porcine tracheal epithelium.
AB  - Because of its possible importance to the etiology of cystic fibrosis lung
      disease, the ion and water transport properties of tracheal epithelium were
      studied. Net liquid flux (J(V)) across porcine tracheal epithelium was measured
      in vitro using blue dextran as a volume probe. Luminal instillation of isosmotic
      sucrose solution (280 mM) induced a small net secretion of liquid (7.0 +/- 1.7 nl
      x cm(-2) x s(-1)), whereas luminal hyposmotic sucrose solutions (220 or 100 mM)
      induced substantial and significant (P < 0.05) liquid absorption (34.5 +/- 12 and
      38.1 +/- 7.3 nl x cm(-2) x s(-1), respectively). When the luminal solution was
      normal (isosmotic) Krebs buffer, liquid was absorbed at 10.2 +/- 1.1 nl x cm(-2)
      x s(-1). Absorptive J(V) was abolished by 100 microM amiloride in the luminal
      solution and significantly reduced when the luminal solution was Na(+)-free Krebs
      solution. Absorptive J(V) was not significantly affected by 300 microM 5-nitro-2
      (3-phenylpropylamino)benzoate or 100 microM diphenylamine-2-carboxylic acid, both
      cystic fibrosis transmembrane conductance regulator protein (CFTR) inhibitors, in
      the instillate but was significantly reduced by 60% when the luminal solution was
      Cl(-)-free Krebs solution. We conclude that water freely permeates porcine
      tracheal epithelium and that absorption of liquid is normally driven by active
      transcellular Na(+) transport and does not require the CFTR.

PMID- 11457797
TI  - Respiratory mechanics and lung histology in normal rats anesthetized with
      sevoflurane.
AB  - Respiratory system, lung, and chest wall mechanical properties were subdivided
      into their resistive, elastic, and viscoelastic/inhomogeneous components in
      normal rats, to define the sites of action of sevoflurane. In addition, we aimed
      to determine the extent to which pretreatment with atropine modified these
      parameters. Twenty-four rats were divided into four groups of six animals each:
      in the P group, rats were sedated (diazepam) and anesthetized with pentobarbital
      sodium; in the S group, sevoflurane was administered; in the AP and AS groups,
      atropine was injected 20 min before sedation/anesthesia with pentobarbital and
      sevoflurane, respectively. Sevoflurane increased lung viscoelastic/inhomogeneous
      pressures and static elastance compared with rats belonging to the P group. In AS
      rats, lung static elastance increased in relation to the AP group. In conclusion,
      sevoflurane anesthesia acted not at the airway level but at the lung periphery,
      stiffening lung tissues and increasing mechanical inhomogeneities. These findings
      were supported by the histological demonstration of increased areas of alveolar
      collapse and hyperinflation. The pretreatment with atropine reduced central and
      peripheral airway secretion, thus lessening lung inhomogeneities.

PMID- 11457798
TI  - Mechanical ventilation of isolated septic rat lungs: effects on surfactant and
      inflammatory cytokines.
AB  - The effects of mechanical ventilation (MV) on the surfactant system and cytokine
      secretion were studied in isolated septic rat lungs. At 23 h after sham surgery
      or induction of sepsis by cecal ligation and perforation (CLP), lungs were
      excised and randomized to one of three groups: 1) a nonventilated group, 2) a
      group subjected to 1 h of noninjurious MV (tidal volume = 10 ml/kg, positive end
      expiratory pressure = 3 cmH(2)O), or 3) a group subjected to 1 h of injurious MV
      (tidal volume = 20 ml/kg, positive end-expiratory pressure = 0 cmH(2)O).
      Nonventilated sham and CLP lungs had similar compliance, normal lung morphology,
      surfactant, and cytokine concentrations. Injurious ventilation decreased
      compliance, altered surfactant, increased cytokines, and induced morphological
      changes compared with nonventilation in sham and CLP lungs. In these lungs, the
      surfactant system was similar in sham and CLP lungs; however, tumor necrosis
      factor-alpha and interleukin-6 levels were significantly higher in CLP lungs. We
      conclude that injurious ventilation altered surfactant independent of sepsis and
      that the CLP lungs were predisposed to the secretion of larger amounts of
      cytokines because of ventilation.

PMID- 11457799
TI  - Activation of the arousal response can impair performance on a simple motor task.
AB  - The purpose of this study was to determine the effect of arousal in men and women
      on the moment-to-moment performance of a simple motor task. We examined the
      control of a precision task in the presence and absence of imposed stressors.
      Twenty-nine subjects (14 men, 15 women; 18--44 yr) were randomly assigned to
      either a control group or one of two stressor groups, Mental Math or Electric
      Shock. Subjects presented with Math and Shock stressors, which lasted 10 min,
      experienced significant increases in cognitive and physiological arousal compared
      with baseline and control subjects. Heart rate, systolic blood pressure, and
      electrodermal activity were elevated 5--80% with presentation of the stressors,
      whereas diastolic blood pressure and salivary cortisol were unchanged. The
      greater levels of cognitive and physiological arousal were associated with
      reductions in steadiness of a pinch grip for the Shock subjects (approximately
      130% reduction from baseline) but not for the subjects in the Math group, who
      experienced heightened arousal but no change in steadiness (10% reduction from
      baseline). Although women exhibited more of a reduction in steadiness than men,
      the effect was largely unrelated to the magnitude of the change in arousal.

PMID- 11457800
TI  - Effect of glutamine and protein supplementation on exercise-induced decreases in
      salivary IgA.
AB  - Postexercise immune impairment has been linked to exercise-induced decrease in
      plasma glutamine concentration. This study examined the possibility of abolishing
      the exercise-induced decrease in salivary IgA through glutamine supplementation
      during and after intense exercise. Eleven athletes performed cycle ergometer
      exercise for 2 h at 75% of maximal oxygen uptake on 3 separate days. Glutamine (a
      total of 17.5 g), protein (a total of 68.5 g/6.2 g protein-bound glutamine), and
      placebo supplements were given during and up to 2 h after exercise. Unstimulated,
      timed saliva samples were obtained before exercise and 20 min, 140 min, 4 h, and
      22 h postexercise. The exercise protocol induced a decrease in salivary IgA (IgA
      concentration, IgA output, and IgA relative to total protein). The plasma
      concentration of glutamine was decreased by 15% 2 h postexercise in the placebo
      group, whereas this decline was abolished by both glutamine and protein
      supplements. None of the supplements, however, was able to abolish the decline in
      salivary IgA. This study does not support that postexercise decrease in salivary
      IgA is related to plasma glutamine concentrations.

PMID- 11457801
TI  - Addition of protein and amino acids to carbohydrates does not enhance
      postexercise muscle glycogen synthesis.
AB  - Ingestion of a protein-amino acid mixture (Pro; wheat protein hydrolysate,
      leucine, and phenylalanine) in combination with carbohydrate (CHO; 0.8 g x kg(-1)
      x h(-1)) has been shown to increase muscle glycogen synthesis after exercise
      compared with the same amount of CHO without Pro. The aim of this study was to
      investigate whether coingestion of Pro also increases muscle glycogen synthesis
      when 1.2 g CHO. kg(-1). h(-1) is ingested. Eight male cyclists performed two
      experimental trials separated by 1 wk. After glycogen-depleting exercise,
      subjects received either CHO (1.2 g x kg(-1) x h(-1)) or CHO+Pro (1.2 g CHO x kg(
      1) x h(-1) + 0.4 g Pro x kg(-1) x h(-1)) during a 3-h recovery period. Muscle
      biopsies were obtained immediately, 1 h, and 3 h after exercise. Blood samples
      were collected immediately after the exercise bout and every 30 min thereafter.
      Plasma insulin was significantly higher in the CHO+Pro trial compared with the
      CHO trial (P < 0.05). No difference was found in plasma glucose or in rate of
      muscle glycogen synthesis between the CHO and the CHO+Pro trials. Although
      coingestion of a protein amino acid mixture in combination with a large CHO
      intake (1.2 g x kg(-1) x h(-1)) increases insulin levels, this does not result in
      increased muscle glycogen synthesis.

PMID- 11457802
TI  - Effects of exhaustive endurance exercise on pulmonary gas exchange and airway
      function in women.
AB  - Seventeen fit women ran to exhaustion (14 +/- 4 min) at a constant speed and
      grade, reaching 95 +/- 3% of maximal O(2) consumption. Pre- and postexercise lung
      function, including airway resistance [total respiratory resistance (Rrs)] across
      a range of oscillation frequencies, was measured, and, on a separate day, airway
      reactivity was assessed via methacholine challenge. Arterial O(2) saturation
      decreased from 97.6 +/- 0.5% at rest to 95.1 +/- 1.9% at 1 min and to 92.5 +/-
      2.6% at exhaustion. Alveolar-arterial O(2) difference (A-aDO(2)) widened to 27 +/
      7 Torr after 1 min and was maintained at this level until exhaustion. Arterial
      PO(2) (Pa(O(2))) fell to 80 +/- 8 Torr at 1 min and then increased to 86 +/- 9
      Torr at exhaustion. This increase in Pa(O(2)) over the exercise duration occurred
      due to a hyperventilation-induced increase in alveolar PO(2) in the presence of a
      constant A-aDO(2). Arterial O(2) saturation fell with time because of increasing
      temperature (+2.6 +/- 0.5 degrees C) and progressive metabolic acidosis (arterial
      pH: 7.39 +/- 0.04 at 1 min to 7.26 +/- 0.07 at exhaustion). Plasma histamine
      increased throughout exercise but was inversely correlated with the fall in
      Pa(O(2)) at end exercise. Neither pre- nor postexercise Rrs, frequency dependence
      of Rrs, nor diffusing capacity for CO correlated with the exercise A-aDO(2) or
      Pa(O(2)). Although several subjects had a positive or borderline
      hyperresponsiveness to methacholine, this reactivity did not correlate with
      exercise-induced changes in Rrs or exercise-induced arterial hypoxemia. In
      conclusion, regardless of the degree of exercise-induced arterial hypoxemia at
      the onset of high-intensity exercise, prolonging exercise to exhaustion had no
      further deleterious effects on A-aDO(2), and the degree of gas exchange
      impairment was not related to individual differences in small or large airway
      function or reactivity.

PMID- 11457803
TI  - Mechanical output impedance of the lung determined from cardiogenic oscillations.
AB  - The beating heart naturally oscillates the lung because of the close
      juxtaposition between these organs producing cardiogenic oscillations in flow
      that can be measured at the mouth when the glottis is open. Correspondingly, if
      the mouth is occluded, the same phenomenon produces cardiogenic pressure
      oscillations that can be measured just distal to the site of occlusion. The
      Fourier-domain ratio of these oscillations in pressure and flow constitutes what
      we call cardiogenic respiratory impedance (Zc). We calculated Zc between about
      1.5 and 10 Hz in relaxed normal subjects at functional residual capacity with
      open glottis. Zc was insensitive to heart rate changes induced by exercise and
      had an imaginary part close to zero at all frequencies investigated. Its real
      part was similar to or smaller than resistance determined by the forced
      oscillation technique. We speculate that Zc measures the flow resistance of the
      central and upper airways of the lung. Zc may be useful as a means of obtaining
      information about lung mechanics without the need for an external source of flow
      perturbations.

PMID- 11457804
TI  - Exercise induces gastric ischemia in healthy volunteers: a tonometry study.
AB  - Heavy physical exercise may cause gastrointestinal signs and symptoms, and,
      although splanchnic blood flow may decrease through redistribution by more than
      50%, it is unclear whether these signs and symptoms relate to gastrointestinal
      ischemia. In 10 healthy volunteers, we studied the effect of exercise on gastric
      mucosal perfusion adequacy using air tonometry. Two relatively short (10 min)
      exercise stages were conducted on a cycle ergometer, aiming for 80 and 100% of
      maximum heart rate, respectively. The intragastric-arterial PCO(2) gradient
      (Delta PCO(2)) was elevated by 1.1 +/- 1.0 kPa over baseline values (-0.1 +/- 0.3
      kPa) only after maximal exercise (P < 0.001). Delta PCO(2) positively correlated
      with the arterial lactate level taken as an index of exercise intensity
      (Spearman's rank test: r = 0.76, P < 0.0001). By bilinear regression analysis, a
      lactate level of 12 mmol/l, above which a sharp rise in the Delta PCO(2)
      occurred, was calculated. We conclude that, in healthy volunteers with normal
      splanchnic vasculature, gastric ischemia may develop during maximal exercise as
      judged from intragastric PCO(2) tonometry.

PMID- 11457805
TI  - Sequential hyperglycemic-euglycemic clamp to assess beta-cell and peripheral
      tissue: studies in female athletes.
AB  - Insulin secretion and rate of utilization (R(d)) of glucose were tested during a
      newly developed sequential clamp in 42 highly trained female athletes (A; 18-69
      yr old) and 14 sedentary control women (C; 18--50 yr old; body mass index <25
      kg/m(2)). The A women were categorized into four age groups: 18--29, 30--39, 40-
      49, and 50--69 yr old. The C women were also grouped by age (18--29 and 40--50 yr
      old). During the three-step clamp (hyperglycemia, return to euglycemia, and
      hyperinsulinemia), glucose turnover was assessed with [3-(3)H]glucose. Among the
      A, the youngest group had the largest first- and second-phase insulin response,
      which was significantly different from the oldest A (P < 0.05). Among the two C
      groups, first-phase response of both groups and second-phase response of the
      older group was higher than respective age-matched A (P < 0.05). During the
      hyperglycemic period, glucose R(d) was similar among A groups and between A and
      C. Despite similar levels of insulin between groups during the hyperinsulinemic
      period (approximately 400 pmol/l), A utilized 36% more glucose than C (P <
      0.001). Glucose R(d) was not different across the age groups of A. This newly
      developed sequential clamp procedure allows assessment of both beta-cell
      sensitivity to glucose and peripheral tissue sensitivity to insulin in a single
      session. We have shown that physical activity improves beta-cell efficiency
      across the age span in women and ameliorates the effect of age on the decline of
      peripheral tissue sensitivity to insulin.

PMID- 11457806
TI  - Frequency characteristics of lung tissue strip during passive stretch and induced
      pneumoconstriction.
AB  - To investigate the frequency-dependent changes of lung tissue mechanics during
      pneumoconstriction, we studied guinea pig subpleural lung strips submitted to a
      multisinusoidal deformation composed of five equal-amplitude discrete frequencies
      ranging between 0.2 and 3.1 Hz. Strips were submitted to graded step stretch
      changes (SS) and to graded histamine stimulation (HS) in organ bath. Elastance,
      resistance, and hysteresivity were calculated at each frequency. The model
      accounting for the relationship between the complex Young's modulus and the
      angular frequency showed that the constant-phase hypothesis was satisfied in SS
      condition. However, HS modified all parameters in the model, and the constant
      phase hypothesis could be rejected for HS of 10(-5) and 10(-3) M. The
      hysteresivity time course changed with angular frequency, but differently in the
      HS and SS conditions. Our results agree with a serial disposition of the
      connective matrix and contractile system in lung tissue. We conclude that
      pneumoconstriction induced significant structural changes at the level of the
      connective matrix.

PMID- 11457807
TI  - Effect of L-NAME on oxygen uptake kinetics during heavy-intensity exercise in the
      horse.
AB  - There is evidence that oxidative enzyme inertia plays a major role in
      limiting/setting the O(2) uptake (VO(2)) response at the transition to higher
      metabolic rates and also that nitric oxide (NO) competitively inhibits VO(2)
      within the electron transport chain. To investigate whether NO is important in
      setting the dynamic response of VO(2) at the onset of high-intensity (heavy
      domain) running in horses, five geldings were run on a treadmill across speed
      transitions from 3 m/s to speeds corresponding to 80% of peak VO(2) with and
      without nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor (20
      mg/kg; order randomized). L-NAME did not alter (both P > 0.05) baseline (3 m/s,
      15.4 +/- 0.3 and 16.2 +/- 0.5 l/min for control and L-NAME, respectively) or end
      exercise VO(2) (56.9 +/- 5.1 and 55.2 +/- 5.8 l/min for control and L-NAME,
      respectively). However, in the L-NAME trial, the primary on-kinetic response was
      significantly (P < 0.05) faster (i.e., reduced time constant, 27.0 +/- 2.7 and
      18.7 +/- 3.0 s for control and L-NAME, respectively), despite no change in the
      gain of VO(2) (P > 0.05). The faster on-kinetic response was confirmed
      independent of modeling by reduced time to 50, 63, and 75% of overall VO(2)
      response (all P < 0.05). In addition, onset of the VO(2) slow component occurred
      earlier (124.6 +/- 11.2 and 65.0 +/- 6.6 s for control and L-NAME, respectively),
      and the magnitude of the O(2) deficit was attenuated (both P < 0.05) in the L
      NAME compared with the control trial. Acceleration of the VO(2) kinetics by L
      NAME suggests that NO inhibition of mitochondrial VO(2) may contribute, in part,
      to the intrinsic metabolic inertia evidenced at the transition to higher
      metabolic rates in the horse.

PMID- 11457808
TI  - Modulation of laryngeal and respiratory pump muscle activities with upper airway
      pressure and flow.
AB  - The hypothesis that upper airway (UA) pressure and flow modulate respiratory
      muscle activity in a respiratory phase-specific fashion was assessed in
      anesthetized, tracheotomized, spontaneously breathing piglets. We generated
      negative pressure and inspiratory flow in phase with tracheal inspiration or
      positive pressure and expiratory flow in phase with tracheal expiration in the
      isolated UA. Stimulation of UA negative pressure receptors with body temperature
      air resulted in a 10--15% enhancement of phasic moving-time-averaged posterior
      cricoarytenoid electromyographic (EMG) activity above tonic levels obtained
      without pressure and flow in the UA (baseline). Stimulation of UA positive
      pressure receptors increased phasic moving-time-averaged thyroarytenoid EMG
      activity above tonic levels by 45% from baseline. The same enhancement of
      posterior cricoarytenoid or thyroarytenoid EMG activity was observed with the
      addition of flow receptor stimulation with room temperature air. Tidal volume and
      diaphragmatic and abdominal muscle activity were unaffected by UA flow and/or
      pressure, whereas respiratory timing was minimally affected. We conclude that
      laryngeal afferents, mainly from pressure receptors, are important in modulating
      the respiratory activity of laryngeal muscles.

PMID- 11457809
TI  - Laryngeal muscle response to phasic and tonic upper airway pressure and flow.
AB  - The hypothesis that respiratory modulation due to upper airway (UA) pressure and
      flow is dependent on stimulus modality and respiratory phase-specific activation
      was assessed in anesthetized, tracheotomized, spontaneously breathing piglets.
      Negative pressure and flow applied to the isolated UA at room or body temperature
      during inspiration only enhanced posterior cricoarytenoid muscle activity from
      that present without UA pressure and flow (baseline) by 15--20%. Time shifting
      the onset of UA flow relative to tracheal flow decreased this enhancement. The
      same enhancement was observed with oscillatory or constant airflow. UA positive
      pressure and flow at room or body temperature applied during expiration only
      enhanced thyroarytenoid muscle activity from baseline by 50--160%. The same
      enhancement was observed with oscillatory or constant airflow at body
      temperature. Constant positive pressure and flow enhanced thyroarytenoid muscle
      activity more than oscillatory pressure and flow at room temperature. We conclude
      that the respiratory modulation of UA afferents is processed in a phase-specific
      fashion and is dependent on stimulus modality (tonic vs. phasic).

PMID- 11457810
TI  - Mechanical stimulation induces pp125(FAK) and pp60(src) activity in an in vivo
      model of trabecular bone formation.
AB  - Utilizing an in vivo model of trabecular bone formation, we demonstrated the
      temporal and spatial activation of pp125(FAK) in response to specific mechanical
      load stimuli. Bone chambers equipped with hydraulic actuators were aseptically
      inserted into each proximal tibial metaphysis of adult, male dogs under general
      anesthesia. The load stimulus consisted of a trapezoidal waveform, with a maximum
      compressive load of 17.8 N, loading rate of 89 N/s, at 1 Hz frequency. One
      chamber was loaded for 2 (120 cycles), 15 (900 cycles), or 30 min (1,800 cycles),
      whereas the contralateral chamber served as unloaded control. Bone chambers were
      biopsied at postload time points of 0, 15, and 45 min. Load-induced activation of
      FAK was rapid, and the duration of activation was dependent on the number of
      applied load cycles. Mechanical stimulation increased the association of FAK with
      Src and the time course of complex formation paralleled the temporal activation
      of FAK. Evaluation of cryosections revealed prominent FAK immunoreactivity among
      marrow fibroblasts and stromal cells.

PMID- 11457811
TI  - Chronic airway infection leads to angiogenesis in the pulmonary circulation.
AB  - In both pulmonary and systemic hypertension, the walls of the arteriolar vessels
      are thickened and the lumen size is reduced, leading to increased total vascular
      resistance. It has been reported previously that chronic airway infection and
      inflammation lead to increased wall thickness in the pulmonary vasculature,
      without the development of pulmonary hypertension. The aim of the present study
      was to examine quantitatively the remodeling of intra-acinar blood vessels in
      chronically infected rat lungs. Adult rats were anesthetized and inoculated
      intratracheally with Pseudomonas aeruginosa (n = 10) incorporated into agar beads
      to induce chronic airway infection. Control groups included rats inoculated with
      sterile agar beads (n = 8) and rats that were not inoculated (n = 6). Chronic
      infection caused vascular wall thickening without reduction in mean lumen radius.
      Furthermore, chronic infection led to increased total length of intra-acinar
      vessels and increased numbers of branch points, demonstrating that angiogenesis
      had occurred. Preservation of lumen size and formation of new parallel pathways
      in the vasculature of chronically infected lungs account for the maintenance of
      normal PVR despite vessel wall remodeling.

PMID- 11457812
TI  - Improved analysis of brachial artery ultrasound using a novel edge-detection
      software system.
AB  - Brachial artery ultrasound is commonly employed for noninvasive assessment of
      endothelial function. However, analysis is observer dependent and susceptible to
      errors. We describe studies on a computerized edge-detection and wall-tracking
      software program to allow more accurate and reproducible measurement. In study 1,
      three purpose-built Perspex phantom arteries, 3.00, 4.00, and 6.00 mm in
      diameter, were measured with the software. There was a mean bias of 11 microm (P
      < 0.001 at each level) between known and measured values; the mean resolving
      power of the software was estimated as 8.3 microm. In study 2, the mean
      intraobserver coefficient of variation of repeated measures of flow-mediated
      dilation (FMD) using the software (6.7%) was significantly lower than that for
      traditional manual measurements using the intima-lumen interfaces (24.8%, P <
      0.05) and intima-media interfaces (32.5%, P < 0.05). In study 3, 24 healthy
      volunteers underwent repeat testing twice within 1 wk; the coefficients of
      variation for between-visit reproducibility of FMD and response to glyceryl
      trinitrate using the software were 14.7 and 17.6%, respectively. Assuming 80%
      power and an alpha of 0.05, eight subjects with matched controls would be
      required, in a parallel designed study, to detect an absolute 2.5% change in FMD.
      In summary, we have developed a semiautomated computerized vascular ultrasound
      analysis system that will improve the power of clinical intervention studies to
      detect small changes in arterial diameter.

PMID- 11457813
TI  - Historical perspective on airway smooth muscle: the saga of a frustrated cell.
AB  - Despite the lack of a clearly defined physiological function, airway smooth
      muscle receives substantial attention because of its involvement in the
      pathogenesis of asthma. Recent investigations have turned to the ways in which
      the muscle is influenced by its dynamic microenvironment. Ordinarily, airway
      smooth muscle presents little problem, even when maximally activated, because
      unending mechanical perturbations provided by spontaneous tidal breathing put
      airway smooth muscle in a perpetual state of "limbo," keeping its contractile
      machinery off balance and unable to achieve its force-generating potential. The
      dynamic microenvironment affects airway smooth muscle in at least two ways: by
      acute changes associated with disruption of myosin binding and by chronic changes
      associated with plastic restructuring of contractile and cytoskeletal filament
      organization. Plastic restructuring can occur when dynamic length changes occur
      between sequential contractile events or within a single contractile event.
      Impairment of these normal responses of airway smooth muscle to its dynamic
      environment may be implicated in airway hyperresponsiveness in asthma.

PMID- 11457814
TI  - Invited review: cross-bridge regulation by thin filament-associated proteins.
AB  - This minireview will cover current concepts on the identity and mechanistic
      function of smooth muscle actin binding proteins that may regulate actin-myosin
      interactions. The potential roles of tropomyosin, caldesmon, calponin, and SM22
      will be discussed. The review, for purposes of brevity, will be nonexhaustive but
      will give an overview of available information on the in vitro biochemistry and
      potential in vivo function of these proteins. Preterm labor is discussed as a
      possible example of where thin filament regulation may be relevant. Considerable
      controversy surrounds the putative physiological significance of these proteins,
      and emphasis will be placed on the need for more experimental work to determine
      the degree to which tissue- and species-specific effects have clouded the
      interpretation of functional data.

PMID- 11457815
TI  - Invited review: focal adhesion and small heat shock proteins in the regulation of
      actin remodeling and contractility in smooth muscle.
AB  - Smooth muscle cells are able to adapt rapidly to chemical and mechanical signals
      impinging on the cell surface. It has been suggested that dynamic changes in the
      actin cytoskeleton contribute to the processes of contractile activation and
      mechanical adaptation in smooth muscle. In this review, evidence for functionally
      important changes in actin polymerization during smooth muscle contraction is
      summarized. The functions and regulation of proteins associated with "focal
      adhesion complexes" (membrane-associated dense plaques) in differentiated smooth
      muscle, including integrins, focal adhesion kinase (FAK), c-Src, paxillin, and
      the 27-kDa small heat shock protein (HSP27) are described. Integrins in smooth
      muscles are key elements of mechanotransduction pathways that communicate with
      and are regulated by focal adhesion proteins that include FAK, c-Src, and
      paxillin as well as proteins known to mediate cytoskeletal remodeling. Evidence
      that functions of FAK and c-Src protein kinases are closely intertwined is
      discussed as well as evidence that focal adhesion proteins mediate key signal
      transduction events that regulate actin remodeling and contraction. HSP27 is
      reviewed as a potentially significant effector protein that may regulate actin
      dynamics and cross-bridge function in response to activation of p21-activated
      kinase and the p38 mitogen-activated protein kinase signaling pathway by
      signaling pathways linked to integrin proteins. These signaling pathways are only
      part of a large number of yet to be defined pathways that mediate acute adaptive
      responses of the cytoskeleton in smooth muscle to environmental stimuli.

PMID- 11457816
TI  - Invited review: arteriolar smooth muscle mechanotransduction: Ca(2+) signaling
      pathways underlying myogenic reactivity.
AB  - The smooth muscle of arterioles responds to an increase in intraluminal pressure
      with vasoconstriction and with vasodilation when pressure is decreased. Such
      myogenic vasoconstriction provides a level of basal tone that enables arterioles
      to appropriately adjust diameter in response to neurohumoral stimuli. Key in this
      process of mechanotransduction is the role of changes in intracellular Ca(2+).
      However, it is becoming clear that considerable complexity exists in the
      spatiotemporal characteristics of the Ca(2+) signal and that changes in
      intracellular Ca(2+) may play roles other than direct effects on the contractile
      process via activation of myosin light-chain phosphorylation. The involvement of
      Ca(2+) may extend to modulation of ion channels and release of Ca(2+) from the
      sarcoplasmic reticulum, alterations in Ca(2+) sensitivity, and coupling between
      cells within the vessel wall. The purpose of this brief review is to summarize
      the current literature relating to Ca(2+) and the arteriolar myogenic response.
      Consideration is given to coupling of Ca(2+) changes to the mechanical stimuli,
      sources of Ca(2+), involvement of ion channels, and spatiotemporal aspects of
      intracellular Ca(2+) signaling.

PMID- 11457817
TI  - Commentary on selected contributions.

PMID- 11457818
TI  - Selected contribution: time course and heterogeneity of contractile responses in
      cultured human airway smooth muscle cells.
AB  - We measured the time course and heterogeneity of responses to contractile and
      relaxing agonists in individual human airway smooth muscle (HASM) cells in
      culture. To this end, we developed a microrheometer based on magnetic twisting
      cytometry adapted with a novel optical detection system. Ferromagnetic beads (4.5
      microm) coated with Arg-Gly-Asp peptide were bound to integrins on the cell
      surface. The beads were twisted in a sinusoidally varying magnetic field at 0.75
      Hz. Oscillatory bead displacements were recorded using a phase-synchronized video
      camera. The storage modulus (cell stiffness; G'), loss modulus (friction; G"),
      and hysteresivity (eta; ratio of G" to G') could be determined with a time
      resolution of 1.3 s. Within 5 s after addition of histamine (100 microM), G'
      increased by 2.2-fold, G" increased by 3.0-fold, and eta increased transiently
      from 0.27 to 0.34. By 20 s, eta decreased to 0.25, whereas G' and G" remained
      above baseline. Comparable results were obtained with bradykinin (1 microM).
      These changes in G', G", and eta measured in cells were similar to but smaller
      than those reported for intact muscle strips. When we ablated baseline tone by
      adding the relaxing agonist dibutyryl cAMP (1 mM), G' decreased within 5 min by
      3.3-fold. With relaxing and contracting agonists, G' could be manipulated through
      a contractile range of 7.3-fold. Cell populations exhibited a log-normal
      distribution of baseline stiffness (geometric SD = 2.8) and a heterogeneous
      response to both contractile and relaxing agonists, partly attributable to
      variability of baseline tone between cells. The total contractile range of the
      cells (from maximally relaxed to maximally stimulated), however, was independent
      of baseline stiffness. We conclude that HASM cells in culture exhibit a clear,
      although heterogeneous, response to contractile and relaxing agonists and express
      the essential mechanical features characteristic of the contractile response
      observed at the tissue level.

PMID- 11457819
TI  - Selected contribution: tryptase-induced PAR-2-mediated Ca(2+) signaling in human
      airway smooth muscle cells.
AB  - Tryptase, the major mast cell product, is considered to play an important role in
      airway inflammation and hyperresponsiveness. Tryptase produces different,
      sometimes opposite, effects on airway responsiveness (bronchoprotection and/or
      airway contraction). This study was designed to examine the effect of human lung
      tryptase and activation of protease-activated receptor (PAR)-2 by synthetic
      activated peptide (AP) SLIGKV-NH(2) on Ca(2+) signaling in human airway smooth
      muscle (HASM) cells. Immunocytochemistry revealed that PAR-2 was expressed by
      HASM cells. Tryptase (7.5--30 mU/ml) induced a concentration-dependent transient
      relative rise in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) that reached 207
      +/- 32 nM (n = 10) measured by indo 1 spectrofluorometry. The protease inhibitors
      leupeptin or benzamidine (100 microM) abolished tryptase-induced [Ca(2+)](i)
      increase. Activation of PAR-2 by AP (1-100 microM) also induced a concentration
      dependent transient rise in [Ca(2+)](i), whereas the reverse peptide produced no
      effect. There was a homologous desensitization of the [Ca(2+)](i) response on
      repeated stimulation with tryptase or AP. U-73122, a specific phospholipase C
      (PLC) antagonist, xestospongin, an inositol trisphosphate (IP(3))-receptor
      antagonist, or thapsigargin, a sarcoplamic Ca(2+)-ATPase inhibitor, abolished
      tryptase-induced [Ca(2+)](i) response, whereas Ca(2+) removal, in the additional
      presence of EGTA, had no effect. Calphostin C, a protein kinase C inhibitor,
      increased PAR-2 [Ca(2+)](i) response. Our results indicate that tryptase
      activates a [Ca(2+)](i) response, which appears as PAR-2 mediated in HASM cells.
      Signal transduction implicates the intracellular Ca(2+) store via PLC activation
      and thus via the IP(3) pathway. This study provides evidence that tryptase, which
      is increasingly recognized as an important mediator in airway inflammation and
      hyperresponsiveness, is also a potent direct agonist at the site of airway smooth
      muscle.

PMID- 11457820
TI  - Selected contribution: effects of ischemia-reperfusion on vascular contractility
      and alpha(1)-adrenergic-receptor signaling in the rat tail artery.
AB  - To determine the effects of ischemia-reperfusion (I/R) on alpha(1)-adrenergic
      receptor (alpha(1)-AR) functions, alpha(1)-AR-mediated contraction, inositol
      phosphate (IP) accumulation, and alpha(1)-AR-G protein coupling were examined in
      the tail arteries of anesthetized rats after 60 min of ischemia and 60 min of
      reperfusion. The contractile response to norepinephrine (NE) was significantly
      increased after I/R, whereas the contractile response to KCl remained unchanged.
      This was accompanied by a 69% increase in NE-stimulated IP accumulation.
      Furthermore, receptor-stimulated coupling of alpha(1a)-AR to G alpha(q/11)
      proteins was increased, whereas the coupling of alpha(1b)-AR or alpha(1d)-AR to
      their G proteins was not altered by I/R. These changes in vascular alpha(1)-AR
      function occurred without concurrent alteration in expression levels of membrane
      alpha(1)-AR subtypes or in the associated G proteins. These data demonstrate that
      I/R increases alpha(1a)-AR-G(q/11) protein coupling and alpha(1)-AR-stimulated IP
      accumulation in the tail artery. The alterations in alpha(1)-AR signaling are
      associated with and may underlie the enhanced contractile response of the tail
      artery to adrenergic stimulation after I/R.

PMID- 11457821
TI  - Cadherin engagement regulates Rho family GTPases.
AB  - The formation of cell-cell adherens junctions is a cadherin-mediated process
      associated with reorganization of the actin cytoskeleton. Because Rho family
      GTPases regulate actin dynamics, we investigated whether cadherin-mediated
      adhesion regulates the activity of RhoA, Rac1, and Cdc42. Confluent epithelial
      cells were found to have elevated Rac1 and Cdc42 activity but decreased RhoA
      activity when compared with low density cultures. Using a calcium switch method
      to manipulate junction assembly, we found that induction of cell-cell junctions
      increased Rac1 activity, and this was inhibited by E-cadherin function-blocking
      antibodies. Using the same calcium switch procedure, we found little effect on
      RhoA activity during the first hour of junction assembly. However, over several
      hours, RhoA activity significantly decreased. To determine whether these effects
      are mediated directly through cadherins or indirectly through engagement of other
      surface proteins downstream from junction assembly, we used a model system in
      which cadherin engagement is induced without cell-cell contact. For these
      experiments, Chinese hamster ovary cells expressing C-cadherin were plated on the
      extracellular domain of C-cadherin immobilized on tissue culture plates. Whereas
      direct cadherin engagement did not stimulate Cdc42 activity, it strongly
      inhibited RhoA activity but increased Rac1 activity. Deletion of the C-cadherin
      cytoplasmic domain abolished these effects.

PMID- 11457822
TI  - The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse.
AB  - Heparan sulfate (HS) is a co-receptor for a number of growth factors, morphogens,
      and adhesion proteins. HS biosynthetic modifications may determine the strength
      and outcome of HS-ligand interactions. We previously described the phenotype of
      mice with a gene-trap mutation in Hs2st, encoding the key HS 2-O-sulfotransferase
      enzyme in HS polymer modification. In contrast to the early developmental failure
      of embryos lacking HS, the onset of abnormalities in the Hs2st(-/-) mice occurs
      only after midgestation, the most dramatic being the complete failure of kidney
      development. Uronate 2-O-sulfates were not detected in the mutant HS, indicating
      a complete loss of function of Hs2st. However, the domain structure of the mutant
      HS is conserved, and compensatory increases in N- and 6-O-sulfation maintain the
      overall charge density. The apparent affinities of the mutant HS for hepatocyte
      growth factor/scatter factor and fibronectin were unchanged but were reduced for
      fibroblast growth factor-1 and -2. Surprisingly, the Hs2st(-/-) cells were able
      to mount an apparently normal signaling response to fibroblast growth factor-1
      and -2 as well as to hepatocyte growth factor/scatter factor.

PMID- 11457823
TI  - A new type of thermoalkalophilic hydrolase of Paucimonas lemoignei with high
      specificity for amorphous polyesters of short chain-length hydroxyalkanoic acids.
AB  - A novel type of hydrolase was purified from culture fluid of Paucimonas (formerly
      Pseudomonas) lemoignei. Biochemical characterization revealed an unusual
      substrate specificity of the purified enzyme for amorphous poly((R)-3
      hydroxyalkanoates) (PHA) such as native granules of natural poly((R)-3
      hydroxybutyrate) (PHB) or poly((R)-3-hydroxyvalerate) (PHV), artificial cholate
      coated granules of natural PHB or PHV, atactic poly((R,S)-3-hydroxybutyrate), and
      oligomers of (R)-3-hydroxybutyrate (3HB) with six or more 3HB units. The enzyme
      has the unique property to recognize the physical state of the polymeric
      substrate by discrimination between amorphous PHA (good substrate) and denatured,
      partially crystalline PHA (no substrate). The pentamers of 3HB or 3HV were
      identified as the main products of enzymatic hydrolysis of native PHB or PHV,
      respectively. No activity was found with any denatured PHA, oligomers of (R)-3HB
      with five or less 3HB units, poly(6-hydroxyhexanoate), substrates of lipases such
      as tributyrin or triolein, substrates for amidases/nitrilases, DNA, RNA, casein,
      N-alpha-benzoyl-l-arginine-4-nitranilide, or starch. The purified enzyme (M(r)
      36,209) was remarkably stable and active at high temperature (60 degrees C), high
      pH (up to 12.0), low ionic strength (distilled water), and in solvents (e.g. n
      propyl alcohol). The depolymerase contained no essential SH groups or essential
      disulfide bridges and was insensitive to high concentrations of ionic (SDS) and
      nonionic (Triton and Tween) detergents. Characterization of the cloned structural
      gene (phaZ7) and the DNA-deduced amino acid sequence revealed no homologies to
      any PHB depolymerase or any other sequence of data banks except for a short
      sequence related to the active site serine of serine hydrolases. A classification
      of the enzyme into a new family (family 9) of carboxyesterases (Arpigny, J. L.,
      and Jaeger, K.-E. (1999) Biochem. J. 343, 177-183) is suggested.

PMID- 11457824
TI  - SeqA protein aggregation is necessary for SeqA function.
AB  - The binding of SeqA protein to hemimethylated GATC sequences is important in the
      negative modulation of chromosomal initiation at oriC, and in the formation of
      SeqA foci necessary for Escherichia coli chromosome segregation. Using gel
      filtration chromotography and glycerol gradient sedimentation, we demonstrate
      that SeqA exists as a homotetramer. SeqA tetramers are able to aggregate or
      multimerize in a reversible, concentration-dependent manner. Using a bacterial
      two-hybrid system, we demonstrate that the N-terminal region of SeqA,
      especifically the 9th amino acid residue, glutamic acid, is required for
      functional SeqA-SeqA interaction. Although the SeqA(E9K) mutant protein,
      containing lysine rather than glutamic acid at the 9th amino acid residue, exists
      as a tetramer, the mutant protein binds to hemimethylated DNA with altered
      binding patterns as compared with wild-type SeqA. Aggregates of SeqA(E9K) are
      defective in hemimethylated DNA binding. Here we demonstrate that proper
      interaction between SeqA tetramers is required for both hemimethylated DNA
      binding and formation of active aggregates. SeqA tetramers and aggregates might
      be involved in the formation of SeqA foci required for the segregation of
      chromosomal DNA as well as the regulation of chromosomal initiation.

PMID- 11457825
TI  - mu-Opioid receptor-mediated ERK activation involves calmodulin-dependent
      epidermal growth factor receptor transactivation.
AB  - Phosphorylation of the MAPK isoform ERK by G protein-coupled receptors involves
      multiple signaling pathways. One of these pathways entails growth factor receptor
      transactivation followed by ERK activation. This study demonstrates that a
      similar signaling pathway is used by the mu-opioid receptor (MOR) expressed in
      HEK293 cells and involves calmodulin (CaM). Stimulation of MOR resulted in both
      epidermal growth factor receptor (EGFR) and ERK phosphorylation. Data obtained
      with inhibitors of EGFR Tyr kinase and membrane metalloproteases support an
      intermediate role of EGFR activation, involving release of endogenous membrane
      bound epidermal growth factor. Previous studies had demonstrated a role for CaM
      in opioid signaling based on direct CaM binding to MOR. To test whether CaM
      contributes to EGFR transactivation and ERK phosphorylation by MOR, we compared
      wild-type MOR with mutant K273A MOR, which binds CaM poorly, but couples normally
      to G proteins. Stimulation of K273A MOR with [D-Ala(2),MePhe(4),Gly
      ol(5)]enkephalin (10-100 nm) resulted in significantly reduced ERK
      phosphorylation. Furthermore, wild-type MOR stimulated EGFR Tyr phosphorylation 3
      fold more than K273A MOR, indicating that direct CaM-MOR interaction plays a key
      role in the transactivation process. Inhibitors of CaM and protein kinase C also
      attenuated [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin-induced EGFR transactivation
      in wild-type (but not mutant) MOR-expressing cells. This novel pathway of EGFR
      transactivation may be shared by other G protein-coupled receptors shown to
      interact with CaM.

PMID- 11457826
TI  - Interleukin-1beta induces chronic activation and de novo synthesis of neutral
      ceramidase in renal mesangial cells.
AB  - The lipid signaling molecule ceramide is formed by the action of acid and neutral
      sphingomyelinases and degraded by acid and neutral ceramidases. Short-term
      stimulation of mesangial cells with the pro-inflammatory cytokine interleukin
      1beta (IL-1beta) leads to a rapid and transient increase in neutral
      sphingomyelinase activity (Kaszkin, M., Huwiler, A., Scholz, K., van den Bosch,
      H., and Pfeilschifter, J. (1998) FEBS Lett. 440, 163-166). In this study, we
      report on a second delayed peak of activation occurring after hours of IL-1beta
      treatment. This second phase of activation was first detectable after 2 h of
      treatment and steadily increased over the next 2 h, reaching maximal values after
      4 h. In parallel, a pronounced increase in neutral ceramidase activity was
      observed, accounting for a constant or even decreased level of ceramide after
      long-term IL-1beta treatment, despite continuous sphingomyelinase activation. The
      increase in neutral ceramidase activity was due to expressional up-regulation, as
      detected by an increase in mRNA levels and enhanced de novo protein synthesis.
      The increase in neutral ceramidase protein levels and activity could be blocked
      dose- dependently by the p38 MAPK inhibitor SB 202190, whereas the classical MAPK
      pathway inhibitor U0126 and the protein kinase C inhibitor Ro 318220 were
      ineffective. Moreover, cotreatment of cells for 24 h with IL-1beta and SB 202190
      led to an increase in ceramide formation. Interestingly, IL-1beta-stimulated
      neutral ceramidase activation was not reduced in mesangial cells isolated from
      mice deficient in MAPK-activated protein kinase-2, which is a downstream
      substrate of p38 MAPK, thus suggesting that the p38 MAPK-mediated induction of
      neutral ceramidase occurs independently of the MAPK-activated protein kinase-2
      pathway. In summary, our results suggest a biphasic regulation of sphingomyelin
      hydrolysis in cytokine-treated mesangial cells with delayed de novo synthesis of
      neutral ceramidase counteracting sphingomyelinase activity and apoptosis. Neutral
      ceramidase may thus represent a novel cytoprotective enzyme for mesangial cells
      exposed to inflammatory stress conditions.

PMID- 11457827
TI  - Saccharomyces cerevisiae protein Pci8p and human protein eIF3e/Int-6 interact
      with the eIF3 core complex by binding to cognate eIF3b subunits.
AB  - Mammalian, plant, and Schizosaccharomyces pombe eukaryotic initiation factor-3
      (eIF3) contains a protein homologous to the product of int-6 (eIF3e), a frequent
      integration site of mouse mammary tumor viruses. By contrast, Saccharomyces
      cerevisiae does not encode a protein closely related to eIF3e/Int-6. Here, we
      characterize a novel S. cerevisiae protein (Pci8p, Yil071cp) that contains a PCI
      (proteasome-COP9 signalosome-eIF3) domain conserved in eIF3e/Int-6. We show that
      both Pci8p and human eIF3e/Int-6 expressed in budding yeast interact with the
      yeast eIF3 complex in vivo and in vitro by binding to a discrete segment of its
      eIF3b subunit Prt1p and that human eIF3e/Int-6 interacts with the human eIF3b
      segment homologous to the Pci8p-binding site of yeast Prt1p. These results refine
      our understanding of subunit interactions in the eIF3 complex and suggest
      structural similarity between human eIF3e/Int-6 and yeast Pci8p. However,
      deletion of PCI8 had no discernible effect on cell growth or translation
      initiation as judged by polysome analysis, suggesting that Pci8p is not required
      for the essential function of eIF3 in translation initiation. Motivated by the
      involvement of Int-6 in transcriptional control, we investigated the effects of
      deleting PCI8 on the total mRNA expression profile by oligonucleotide microarray
      analysis and found reduced mRNA levels for a subset of heat shock proteins in the
      pci8Delta mutant. We discuss possible dual functions of Pci8p and Int-6 in
      transcriptional and translational control.

PMID- 11457828
TI  - TATA-binding protein-associated factors enhance the recruitment of RNA polymerase
      II by transcriptional activators.
AB  - Transcription factor (TF) IID, comprised of the TATA-binding protein (TBP) and
      TBP-associated factors (TAFs), is a general transcription factor required for RNA
      polymerase II (pol II) transcription on most eukaryotic genes. Recent findings
      that TAFs may not be globally required for activator-dependent transcription in
      vivo and in vitro and that both TAF-dependent and TAF-independent promoters are
      found in yeast suggest that transcriptional activation can occur through at least
      two different pathways, depending on the presence or absence of TAFs. Using order
      of-addition and template challenge assays performed in a human cell-free
      transcription system reconstituted with recombinant general transcription factors
      (TFIIB, TBP, TFIIE, TFIIF), a recombinant general cofactor (PC4), and highly
      purified epitope-tagged multiprotein complexes (TFIID, TFIIH, pol II), we
      demonstrate that when TBP is used as the TATA-binding factor transcriptional
      activators such as Gal4-VP16 and human papillomavirus E2 mainly function by
      facilitating pol II entry to the promoter region. In contrast, when TFIID is used
      as the TATA-binding factor, promoter recognition by TFIID appears to be the rate
      limiting step facilitated by transcriptional activators during preinitiation
      complex assembly. Using protein-protein pull-down and far-Western analyses, we
      further show that the presence of TAFs in TFIID facilitates the recruitment of
      pol II by transcriptional activators, thereby switching the rate-limiting step
      from pol II entry to promoter recognition. Our findings thus provide distinct
      molecular mechanisms for TAF-independent and TAF-dependent activation.

PMID- 11457829
TI  - The hepatitis B virus X protein induces HIV-1 replication and transcription in
      synergy with T-cell activation signals: functional roles of NF-kappaB/NF-AT and
      SP1-binding sites in the HIV-1 long terminal repeat promoter.
AB  - Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus type-1
      (HIV-1) is relatively common. However, the impact of this co-infection on the
      clinical outcome of HIV infection has not been elucidated. We herein demonstrate
      that the HBV X protein (HBx) superinduces ongoing HIV-1 replication and HIV-1
      long terminal repeat (LTR) transcription by synergizing with Tat protein and with
      T-cell activation signals. Although HBx cooperated with mitogenic stimuli in the
      induction of reporter plasmids harboring the HIV-1 kappaB enhancer, in both a NF
      kappaB-dependent manner and a NF-AT-dependent manner, deletion of this element
      from the LTR did not affect the HBx-mediated up-regulation in the presence of Tat
      and/or mitogens. In contrast, mutation of the proximal LTR Sp1-binding sites
      abolished the HBx-mediated synergistic activation, but only when it was
      accompanied by deletion of the kappaB enhancer. When HBx was targeted to the
      nucleus, its ability to synergize with cellular activation stimuli was
      maintained. Furthermore, mutations of HBx affecting its interaction with the
      basal transcription machinery abrogated the synergistic activation by HBx,
      suggesting that this protein exerts its function by acting as a nuclear co
      activator. These results indicate that HBx could contribute to a faster
      progression to AIDS in HBV-HIV co-infected individuals.

PMID- 11457830
TI  - Modular design of Gbeta as the basis for reversible specificity in effector
      stimulation.
AB  - The G protein Gbetagamma subunit complex stimulates effectors by direct
      interactions utilizing extensive Gbeta regions over the surface of its propeller
      structure that faces the Galpha subunit. Our previous experiments have shown the
      resolved functions of signal transfer and general binding for Gbeta regions
      involved in stimulation of the effector phospholipase C-beta2, PLC-beta2, within
      the region Gbeta-(86-135), which comprises three beta strands arranged in a
      structurally contiguous fashion (Buck, E., Li, J., Chen, Y., Weng, G., Sacarlata,
      S., and Iyengar, R. (1999) Science 283, 1332-1335). This raises an important
      question as to why mutagenesis studies indicate that an extensive set of sites
      all over the Gbeta propeller structure and outside the 86-135 region are involved
      in Gbeta regulation of PLC-beta2. Using peptides to define functions of these
      Gbeta regions, we find that Gbeta signaling to PLC-beta2 relies on a collection
      of modular signal transfer and general binding units, each with lower apparent
      affinity relative to Gbetagamma-PLC interactions. Gbeta-(42-54) functions as a
      signal transfer region, Gbeta-(228-249) and Gbeta-(321-340) function in general
      binding, and Gbeta-(64-84) and Gbeta-(300-313) seem to play a structural role
      rather than a direct contact with the effector. A substitution within the Gbeta
      (42-54) signal transfer region that increases the K(act) of this peptide for PLC
      beta2 is accompanied by an increase in the observed maximal extent of signal
      transfer. We conclude that the lower K(act) for individual signal transfer
      regions may result in a decrease in the maximal effect of signal transfer. The
      spatial resolution of the signal transfer and general binding regions over a wide
      surface of Gbeta allow geometrical constraints to achieve specificity even with
      relatively low affinity interactions.

PMID- 11457831
TI  - Function of the Rho family GTPases in Ras-stimulated Raf activation.
AB  - Ras plays an essential role in activation of Raf kinase which is directly
      responsible for activation of the MEK-ERK kinase pathway. A direct protein
      protein interaction between Ras and the N-terminal regulatory domain of Raf is
      critical for Raf activation. However, association with Ras is not sufficient to
      activate Raf in vitro, indicating that Ras must activate some other biochemical
      events leading to activation of Raf. We have observed that RasV12Y32F and
      RasV12T35S mutants fail to activate Raf, yet retain the ability to interact with
      Raf. In this report, we showed that RasV12Y32F and RasV12T35S can cooperate with
      members of the Rho family GTPases to activate Raf while alone the Rho family
      GTPase is not effective in Raf activation. A dominant negative mutant of Rac or
      RhoA can block Raf activation by Ras. The effect of Rac or Cdc42 can be
      substituted by the Pak kinase, which is a direct downstream target of Rac/Cdc42.
      Furthermore, expression of a kinase inactive mutant of Pak or the N-terminal
      inhibitory domain of Pak1 can block the effect of Rac or Cdc42. In contrast, Pak
      appears to play no direct role in relaying the signal from RhoA to Raf,
      indicating that RhoA utilizes a different mechanism than Rac/Cdc42. Membrane
      associated but not cytoplasmic Raf can be activated by Rac or RhoA. Our data
      support a model by which the Rho family small GTPases play an important role to
      mediate the activation of Raf by Ras. Ras, at least, has two distinct functions
      in Raf activation, recruitment of Raf to the plasma membrane by direct binding
      and stimulation of Raf activating kinases via the Rho family GTPases.

PMID- 11457832
TI  - The GATA transcription factors GLN3 and GAT1 link TOR to salt stress in
      Saccharomyces cerevisiae.
AB  - One of the most recent functions assigned to the TOR signaling pathway in yeast
      is the coordination of the transcription of genes involved in nutrient
      utilization. Here we show that transcription of ENA1, a gene encoding a lithium
      and sodium ion transporter essential for salt tolerance in yeast, is controlled
      by the TOR signaling pathway. First, ENA1 expression is strongly induced under
      TOR-inactivating conditions. Second, the absence of the TOR-controlled GATA
      transcription factors GLN3 and GAT1 results in reduced basal and salt-induced
      expression of ENA1. Third, a gln3 gat1 mutant displays a pronounced sensitivity
      to high concentrations of lithium and sodium. Fourth, TOR1, similar to ENA1, is
      required for growth under saline stress conditions. In summary, our results
      suggest that TOR plays a role in the general response to saline stress by
      regulating the transcription of ENA1 via GLN3 and GAT1.

PMID- 11457833
TI  - Nonsense mutations in cspA cause ribosome trapping leading to complete growth
      inhibition and cell death at low temperature in Escherichia coli.
AB  - CspA, the major cold shock protein of Escherichia coli, is dramatically induced
      immediately after cold shock. CspA production is transient and reduces to a low
      basal level when cells become adapted. Here we show that expression from
      multicopy plasmids of mutant cspA mRNAs bearing nonsense mutations in the coding
      region caused sustained high levels of the mutant mRNAs at low temperature,
      resulting in complete inhibition of cell growth ultimately leading to cell death.
      We demonstrate that the observed growth inhibition was caused by largely
      exclusive occupation of cellular ribosomes by the mutant cspA mRNAs. Such
      sequestration of ribosomes even occurs without a single peptide bond formation,
      implying that the robust translatability of the cspA mRNA is determined at the
      step of initiation. Further analysis demonstrated that the downstream box of the
      cspA mRNA was dispensable for the effect, whereas the upstream box of the mRNA
      was essential. Our system may offer a novel means to study sequence or structural
      elements involved in the translation of the cspA mRNA and may also be utilized to
      regulate bacterial growth at low temperature.

PMID- 11457834
TI  - Activation of mitogen-activated protein kinase by membrane-targeted Raf chimeras
      is independent of raft localization.
AB  - Binding of proteins to the plasma membrane can be achieved with various membrane
      targeting motifs, including combinations of fatty acids, isoprenoids, and basic
      domains. In this study, we investigate whether attachment of different membrane
      targeting motifs influences the signaling capacity of membrane-bound signal
      transduction proteins by directing the proteins to different membrane
      microdomains. We used c-Raf-1 as a model for a signaling protein that is
      activated when membrane-bound. Three different membrane targeting motifs from K
      Ras, Fyn, and Src proteins were fused to the N or C terminus of Raf-1. The
      ability of the modified Rafs to initiate MAPK signaling was then investigated.
      All three modified Raf-1 constructs activated MAPK to nearly equivalent levels.
      The extent of localization of the Raf-1 constructs to membrane microdomains known
      as rafts did not correlate with the level of MAPK activation. Moreover, treatment
      of cells with the raft disrupting drug methyl-beta-cyclodextrin (MbetaCD) caused
      activation of MAPK to levels equivalent to those achieved with membrane-targeted
      Raf constructs. The use of pharmacological agents as well as dominant negative
      mutants revealed that MAPK activation by MbetaCD proceeds via a phosphoinositide
      3-kinase-dependent mechanism that is Ras/Raf-independent. We conclude that
      cholesterol depletion from the plasma membrane by MbetaCD constitutes an
      alternative pathway for activating MAPK.

PMID- 11457835
TI  - Insulin-responsive nuclear proteins facilitate Sp1 interactions with the insulin
      like growth factor-I gene.
AB  - The diabetes-induced decrease in insulin-like growth factor-I transcription
      appears to be mediated by footprint region V in exon 1. Since region V contains
      both an Sp1 site and an AT-rich element that recognizes an insulin-responsive
      binding protein (IRBP), we tested the hypothesis that Sp1 interactions are
      facilitated by an IRBP. Binding of nuclear extracts to region V probes was
      reduced by mutational or chemical interference with the AT-rich element. Blocking
      the AT site also reduced interactions of Sp1 with region V in vitro and blunted
      transactivation of region V reporter constructs by Sp1 in vivo. Sp1 binding was
      enhanced by small quantities of hepatic nuclear extracts, but enhancement was
      reduced by the AT mutation and abolished by a 5-base pair insertion between the
      AT-rich and GC-rich sites, and transactivation by Sp1 in vivo was diminished by
      inserting bases between the AT-rich and GC-rich elements. However, treating cells
      with insulin increased the ability of nuclear extracts to enhance Sp1 binding.
      These findings indicate that the presence of the AT-rich element is essential for
      the actions of Sp1 in vitro and in vivo, and the combination of both spacing
      requirements and insulin responsiveness suggests that IRBP may interact directly
      with Sp1.

PMID- 11457836
TI  - Single nucleotide polymorphisms in the human mu opioid receptor gene alter basal
      G protein coupling and calmodulin binding.
AB  - The mu opioid receptor (MOR) plays a central role in mediating acute and chronic
      effects of narcotic drugs. Three rare single nucleotide polymorphisms in the hMOR
      gene have been identified that cause amino acid substitutions in the third
      intracellular (i3) loop of MOR (R260H, R265H, and S268P). Genotyping 252
      individuals of the Coriell collection identified one allele encoding the R265H
      MOR variant and a new variant encoding D274N-MOR. Variants R260H-, R265H-, and
      S268P-MOR were constructed and transfected into HEK293 cells. Morphine stimulated
      G protein coupling of the three receptor variants to a maximal level approaching
      that of wild type MOR. In contrast, spontaneous, agonist-independent (basal) MOR
      signaling, proposed to play a role in opioid tolerance and dependence, was
      significantly reduced for R260H- and R265H-MOR. Moreover, domains within the i3
      loop of MOR have been shown to interact with both G proteins and calmodulin
      (CaM). CaM binding was deficient for variants R265H- and S268P-MOR, suggesting
      that domains for G protein coupling and CaM binding overlap partially. Morphine
      pretreatment significantly enhanced basal G protein coupling of wild type MOR,
      which is thought to result from release of CaM. In contrast basal G protein
      coupling activity of the three variants was unaffected by morphine pretreatment
      consistent with diminished CaM regulation, low basal activity, or both. In
      conclusion, each of the three single nucleotide polymorphisms mapping to the i3
      loop of MOR caused substantial changes in basal G protein coupling, CaM binding,
      or both. Carriers of the mutant alleles might display altered responses to
      narcotic analgesics.

PMID- 11457837
TI  - Inhibition of DNA cross-linking by mitomycin C by peroxidase-mediated oxidation
      of mitomycin C hydroquinone.
AB  - Mitomycin C requires reductive activation to cross-link DNA and express
      anticancer activity. Reduction of mitomycin C (40 microm) by sodium borohydride
      (200 microm) in 20 mm Tris-HCl, 1 mm EDTA at 37 degrees C, pH 7.4, gives a 50-60%
      yield of the reactive intermediate mitomycin C hydroquinone. The hydroquinone
      decays with first order kinetics or pseudo first order kinetics with a t(12) of
      approximately 15 s under these conditions. The cross-linking of T7 DNA in this
      system followed matching kinetics, with the conversion of mitomycin C
      hydroquinone to leuco-aziridinomitosene appearing to be the rate-determining
      step. Several peroxidases were found to oxidize mitomycin C hydroquinone to
      mitomycin C and to block DNA cross-linking to various degrees. Concentrations of
      the various peroxidases that largely blocked DNA cross-linking, regenerated 10
      70% mitomycin C from the reduced material. Thus, significant quantities of
      products other than mitomycin C were produced by the peroxidase-mediated
      oxidation of mitomycin C hydroquinone or products derived therefrom. Variations
      in the sensitivity of cells to mitomycin C have been attributed to differing
      levels of activating enzymes, export pumps, and DNA repair. Mitomycin C
      hydroquinone-oxidizing enzymes give rise to a new mechanism by which oxic/hypoxic
      toxicity differentials and resistance can occur.

PMID- 11457838
TI  - Protein kinase A regulates expression of p27(kip1) and cyclin D3 to suppress
      proliferation of leukemic T cell lines.
AB  - Peripheral homeostasis and tolerance requires the suppression or removal of
      excessive or harmful T lymphocytes. This can occur either by apoptosis through
      active antigen-induced death or cytokine withdrawal. Alternatively, T cell
      activation can be suppressed by agents that activate the cAMP-dependent protein
      kinase (PKA) signaling pathway, such as prostaglandin E2. Stimulation of PKA
      inhibits lymphocyte proliferation and immune effector functions. Here we have
      investigated the mechanism by which activation of PKA induces inhibition of
      proliferation in human leukemic T cell lines. Using a variety of agents that
      stimulate PKA, we can arrest Jurkat and H9 leukemic T cells in the G(1) phase of
      the cell cycle, whereas cell viability is hardly affected. This G(1) arrest is
      associated with an inhibition of cyclin D/Cdk and cyclin E/Cdk kinase activity.
      Interestingly, expression of cyclin D3 is rapidly reduced by PKA activation,
      whereas expression of the Cdk inhibitor p27(kip1) is induced. Ectopic expression
      of cyclin D3 can override the growth suppression induced by PKA activation to
      some extent, indicating that growth inhibition of leukemic T cells by PKA
      activation is partially dependent on down-regulation of cyclin D3 expression.
      Taken together our data suggest that immunosuppression by protein kinase A
      involves regulation of both cyclin D3 and p27(kip1) expression.

PMID- 11457839
TI  - Interaction of Maf transcription factors with Pax-6 results in synergistic
      activation of the glucagon promoter.
AB  - In the endocrine pancreas, alpha-cell-specific expression of the glucagon gene is
      mediated by DNA-binding proteins that interact with the G1 proximal promoter
      element. Among these proteins, the paired domain transcription factor Pax-6 has
      been shown to bind to G1 and to transactivate glucagon gene expression. Close to
      the Pax-6-binding site, we observed the presence of a binding site for a basic
      leucine zipper transcription factor of the Maf family. In the present study, we
      demonstrate the presence of Maf family members in the endocrine pancreas that
      bind to G1 and transactivate glucagon promoter expression. In transient
      transfection experiments, we found that the transactivating effect on the
      glucagon promoter was greatly enhanced by the simultaneous expression of Maf
      transcription factors and Pax-6. This enhancement on glucagon transactivation
      could be correlated with the ability of these proteins to interact together but
      does not require binding of Maf proteins to the G1 element. Furthermore, we found
      that Maf enhanced the Pax-6 DNA binding capacity. Our data indicate that Maf
      transcription factors may contribute to glucagon gene expression in the pancreas.

PMID- 11457840
TI  - Modulation of myosin function by isoform-specific properties of Saccharomyces
      cerevisiae and muscle tropomyosins.
AB  - Tropomyosin is an extended coiled-coil protein that influences actin function by
      binding longitudinally along thin filaments. The present work compares cardiac
      tropomyosin and the two tropomyosins from Saccharomyces cerevisiae, TPM1 and
      TPM2, that are much shorter than vertebrate tropomyosins. Unlike cardiac
      tropomyosin, the phase of the coiled-coil-forming heptad repeat of TPM2 is
      discontinuous; it is interrupted by a 4-residue deletion. TPM1 has two such
      deletions, which flank the 38-residue partial gene duplication that causes TPM1
      to span five actins instead of the four of TPM2. Each of the three tropomyosin
      isoforms modulates actin-myosin interactions, with isoform-specific effects on
      cooperativity and strength of myosin binding. These different properties can be
      explained by a model that combines opposite effects, steric hindrance between
      myosin and tropomyosin when the latter is bound to a subset of its sites on
      actin, and also indirect, favorable interactions between tropomyosin and myosin,
      mediated by mutually promoted changes in actin. Both of these effects are
      influenced by which tropomyosin isoform is present. Finally, the tropomyosins
      have isoform-specific effects on in vitro sliding speed and on the myosin
      concentration dependence of this movement, suggesting that non-muscle tropomyosin
      isoforms exist, at least in part, to modulate myosin function.

PMID- 11457841
TI  - Identification and pharmacological correction of a membrane trafficking defect
      associated with a mutation in the sulfonylurea receptor causing familial
      hyperinsulinism.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a genetic disorder
      characterized by excess secretion of insulin and hypoglycemia. In most patients,
      the disease is caused by mutations in sulfonylurea receptor-1 (SUR1), which, in
      association with Kir6.2, constitutes the functional ATP-sensitive potassium
      (K(ATP)) channel of the pancreatic beta-cell. Previous studies reported that
      coexpression of the PHHI mutant R1394H-SUR1 with Kir6.2 in COS cells produces no
      functional channels. To investigate if the loss of function could be due to
      impaired trafficking of mutant channels to the cell membrane, we have
      cotransfected wild-type and mutant SUR1 subunits with Kir6.2 into HEK293 cells
      and examined their cellular localization by immunofluorescent staining. Our
      results show that unlike the wild-type subunits, which showed fluorescence at the
      cell surface, the mutant subunits displayed fluorescence in punctate structures.
      Co-immunostaining with antibodies against organelle-specific marker proteins
      identified these structures as the trans-Golgi network. Limited localization in
      clathrin-positive, but transferrin receptor-negative vesicles was also observed.
      The post-endoplasmic reticulum localization suggests that the mutation does not
      impair the folding and assembly of the channels so as to cause its retention by
      the endoplasmic reticulum. Diazoxide, a K(ATP) channel opener drug that is used
      in the treatment of PHHI, restored the surface expression in a manner that could
      be prevented by the channel blocker glibenclamide. When expressed in Xenopus
      oocytes, R1394H-SUR1 formed functional channels with Kir6.2, indicating that the
      primary consequence of the mutation is impairment of trafficking rather than
      function. Thus, our data uncover a novel mechanism underlying the therapeutic
      action of diazoxide in the treatment of PHHI, i.e. its ability to recruit
      channels to the membrane. Furthermore, this is the first report to describe a
      trafficking disorder effecting retention of mutant proteins in the trans-Golgi
      network.

PMID- 11457842
TI  - Motor function and regulation of myosin X.
AB  - Myosin X is a member of the diverse myosin superfamily that is ubiquitously
      expressed in various mammalian tissues. Although its association with actin in
      cells has been shown, little is known about its biochemical and mechanoenzymatic
      function at the molecular level. We expressed bovine myosin X containing the
      entire head, neck, and coiled-coil domain and purified bovine myosin X in Sf9
      cells. The Mg(2+)-ATPase activity of myosin X was significantly activated by
      actin with low K(ATP). The actin-activated ATPase activity was reduced at Ca(2+)
      concentrations above pCa 5 in which 1 mol of calmodulin light chain dissociates
      from the heavy chain. Myosin X translocates F-actin filaments with the velocity
      of 0.3 microm/s with the direction toward the barbed end. The actin translocating
      activity was inhibited at concentrations of Ca(2+) at pCa 6 in which no
      calmodulin dissociation takes place, suggesting that the calmodulin dissociation
      is not required for the inhibition of the motility. Unlike class V myosin, which
      shows a high affinity for F-actin in the presence of ATP, the K(actin) of the
      myosin X ATPase was much higher than that of myosin V. Consistently nearly all
      actin dissociated from myosin X in the presence of ATP. ADP did not significantly
      inhibit the actin-activated ATPase activity of myosin X, suggesting that the ADP
      release step is not rate-limiting. These results suggest that myosin X is a
      nonprocessive motor. Consistently myosin X failed to support the actin
      translocation at low density in an in vitro motility assay where myosin V, a
      processive motor, supports the actin filament movement.

PMID- 11457843
TI  - The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of
      the orphan G protein-coupled receptor GPR54.
AB  - Natural peptides displaying agonist activity on the orphan G protein-coupled
      receptor GPR54 were isolated from human placenta. These 54-, 14,- and 13-amino
      acid peptides, with a common RF-amide C terminus, derive from the product of KiSS
      1, a metastasis suppressor gene for melanoma cells, and were therefore designated
      kisspeptins. They bound with low nanomolar affinities to rat and human GPR54
      expressed in Chinese hamster ovary K1 cells and stimulated PIP(2) hydrolysis,
      Ca(2+) mobilization, arachidonic acid release, ERK1/2 and p38 MAP kinase
      phosphorylation, and stress fiber formation but inhibited cell proliferation.
      Human GPR54 was highly expressed in placenta, pituitary, pancreas, and spinal
      cord, suggesting a role in the regulation of endocrine function. Stimulation of
      oxytocin secretion after kisspeptin administration to rats confirmed this
      hypothesis.

PMID- 11457844
TI  - Induction of angiogenesis by expression of soluble type II transforming growth
      factor-beta receptor in mouse hepatoma.
AB  - The biological effect of transforming growth factor-beta (TGF-beta) is cell type
      specific and complex. The precise role of TGF-beta is not clear in vivo. To
      elucidate the regulation mechanism of endogenous TGF-beta on hepatoma
      progression, we modified the MH129F mouse hepatoma cell with a retroviral vector
      encoding the extracellular region of type II TGF-beta receptor (TRII). Soluble
      TRII (TRIIs) blocked TGF-beta binding to TRII on the membrane of hepatoma cells.
      Growth of MH129F cells was inhibited by TGF-beta1 treatment; however, soluble
      TRII-overexpressing cells (MH129F/TRIIs) did not show any change in proliferation
      after TGF-beta1 treatment. MH129F/TRIIs cells also increased vascular endothelial
      growth factor (VEGF) expression, endothelial cell migration, and tube formation.
      Implantation of MH129F/TRIIs cells into C3H/He mice showed the significantly
      enhanced tumor formation. According to Western blot and protein kinase C assay,
      the expression of VEGF, KDR/flk-1 receptor, and endothelial nitric-oxide synthase
      was enhanced, and the phosphorylation activity of protein kinase C was increased
      up to 3.7-fold in MH129F/TRIIs tumors. Finally, a PECAM-1-stained intratumoral
      vessel was shown to be 4.2-fold higher in the MH129F/TRIIs tumor. These results
      indicate that VEGF expression is up-regulated by a blockade of endogenous TGF
      beta signaling in TGF-beta-sensitive hepatoma cells and then stimulates
      angiogenesis and tumorigenicity. Therefore, we suggest that endogenous TGF-beta
      is a major regulator of the VEGF/flk-1-mediated angiogenesis pathway in hepatoma
      progression.

PMID- 11457845
TI  - A catalytic loop within Pseudomonas aeruginosa exotoxin A modulates its
      transferase activity.
AB  - Mutagenesis techniques were used to replace two loop regions within the catalytic
      domain of Pseudomonas aeruginosa exotoxin A (ETA) with functionally silent
      polyglycine loops. The loop mutant proteins, designated polyglycine Loops N and
      C, were both less active than the wild-type enzyme. However, the polyglycine Loop
      C mutant protein, replaced with the Gly(483)-Gly(490) loop, showed a much greater
      loss of enzymatic activity than the polyglycine Loop N protein. The former mutant
      enzyme exhibited an 18,000-fold decrease in catalytic turnover number (k(cat)),
      with only a marginal effect on the K(m) value for NAD(+) and the eukaryotic
      elongation factor-2 binding constant. Furthermore, alanine-scanning mutagenesis
      of this active-site loop region revealed the specific pattern of a critical
      region for enzymatic activity. Binding and kinetic data suggest that this loop
      modulates the transferase activity between ETA and eukaryotic elongation factor-2
      and may be responsible for stabilization of the transition state for the
      reaction. Sequence alignment and molecular modeling also identified a similar
      loop within diphtheria toxin, a functionally and structurally related class A-B
      toxin. Based on these results and the similarities between ETA and diphtheria
      toxin, we propose that this catalytic subregion represents the first report of a
      diphthamide-specific ribosyltransferase structural motif. We expect these
      findings to further the development of pharmaceuticals designed to prevent ETA
      toxicity by disrupting the stabilization of the transition state during the ADP
      ribose transfer event.

PMID- 11457846
TI  - High glucose stimulates early response gene c-Myc expression in rat pancreatic
      beta cells.
AB  - Glucose-induced insulin secretion from hyperglycemic 90% pancreatectomized rats
      is markedly impaired, possibly because of loss of beta cell differentiation.
      Association of these changes with beta cell hypertrophy, increased mRNA levels of
      the transcription factor c-Myc, and their complete normalization by phlorizin
      treatment suggested a link between chronic hyperglycemia, increased c-Myc
      expression, and altered beta cell function. In this study, we tested the effect
      of hyperglycemia on rat pancreatic islet c-Myc expression both in vivo and in
      vitro. Elevation of plasma glucose for 1-4 days (glucose infusion/clamp) was
      followed by parallel increases in islet mRNA levels (relative to TATA-binding
      protein) of c-Myc and two of its target genes, ornithine decarboxylase and
      lactate dehydrogenase A. Similar changes were observed in vitro upon stimulation
      of cultured islets or purified beta cells with 20 and 30 mmol.liter(-1) glucose
      for 18 h. These effects of high glucose were reproduced by high potassium-induced
      depolarization or dibutyryl-cAMP and were inhibited by agents decreasing
      cytosolic Ca(2+) or cAMP concentrations. In conclusion, the expression of the
      early response gene c-Myc in rat pancreatic beta cells is stimulated by high
      glucose in a Ca(2+)-dependent manner and by cAMP. c-Myc could therefore
      participate to the regulation of beta cell growth, apoptosis, and differentiation
      under physiological or pathophysiological conditions.

PMID- 11457847
TI  - Cholesterol esterification by host and parasite is essential for optimal
      proliferation of Toxoplasma gondii.
AB  - Upon host cell invasion the apicomplexan parasite Toxoplasma gondii resides in a
      specialized compartment termed the parasitophorous vacuole that is derived from
      the host cell membrane but modified by the parasite. Despite the segregation of
      the parasitophorous vacuole from the host endocytic network, the intravacuolar
      parasite has been shown to acquire cholesterol from the host cell. In order to
      characterize further the role of sterol metabolism in T. gondii biology, we
      focused our studies on the activity of acyl-CoA:cholesterol acyltransferase
      (ACAT), a key enzyme for maintaining the intracellular homeostasis of cholesterol
      through the formation of cholesterol esters. In this study, we demonstrate that
      ACAT and cholesterol esters play a crucial role in the optimal replication of T.
      gondii. Moreover, we identified ACAT activity in T. gondii that can be modulated
      by pharmacological ACAT inhibitors with a consequent detrimental effect on
      parasite replication.

PMID- 11457848
TI  - Free fatty acids activate a vigorous Ca(2+):2H(+) antiport activity in yeast
      mitochondria.
AB  - The accumulation and retention of Ca(2+) by yeast mitochondria (Saccharomyces
      cerevisiae) mediated by ionophore ETH 129 occurs with a variable efficiency in
      different preparations. Ineffective Ca(2+) transport and a depressed membrane
      potential occur in parallel, are exacerbated in parallel by exogenous free fatty
      acids, and are corrected in parallel by the addition of bovine serum albumin.
      Bovine serum albumin is not required to develop a high membrane potential when
      either Ca(2+) or ETH 129 are absent, and when both are present membrane potential
      is restored by the addition of EGTA in a concentration-dependent manner.
      Respiration and swelling data indicate that the permeability transition pore does
      not open in yeast mitochondria that are treated with Ca(2+) and ETH 129, whereas
      fatty acid concentration studies and the inaction of carboxyatractyloside
      indicate that fatty acid-derived uncoupling does not underlie the other
      observations. It is concluded that yeast mitochondria contain a previously
      unrecognized Ca(2+):2H(+) antiporter that is highly active in the presence of
      free fatty acids and leads to a futile cycle of Ca(2+) accumulation and release
      when exogenous Ca(2+) and ETH 129 are available. It is also shown that isolated
      yeast mitochondria degrade their phospholipids at a relatively rapid rate. The
      activity responsible is also previously unrecognized. It is Ca(2+)-independent,
      little affected by the presence or absence of a respiratory substrate, and leads
      to the hydrolysis of ester linkages at both the sn-1 and sn-2 positions of the
      glycerophospholipids. The products of this activity, through their actions on the
      antiporter, explain the variable behavior of yeast mitochondria treated with
      Ca(2+) plus ETH 129.

PMID- 11457849
TI  - Mechanosensitive transcription factors involved in endothelin B receptor
      expression.
AB  - Growing evidence suggests an involvement of the endothelin B receptor (ET(B)-R)
      in blood pressure-dependent arterial remodeling. To study the molecular
      mechanisms leading to deformation-induced ET(B)-R expression, we have cultured
      rat aortic smooth muscle cells on flexible elastomers and, when grown to 70%
      confluence, periodically stretched them for 6 h (15% elongation, 0.5 Hz). The
      cells responded with an increase both in ET(B)-R mRNA (12-fold compared with
      control) and protein (4-fold). According to nuclear run-on analysis this increase
      in ET(B)-R expression occurred at the level of transcription. Among various
      kinase pathways, Rho kinase (ROCK) and p38 mitogen-activated protein kinase (p38
      MAPK) mediated part of the deformation-induced increase in ET(B)-R expression, as
      judged by the inhibitory effect of Y27632 (1 microm, 38% inhibition) and SB202190
      (10 microm, 44% inhibition), respectively. Gel shift assaying of the three
      transcription factors principally activated by these kinases revealed a transient
      deformation-induced activation of activator protein-1 (AP-1) and CCAAT/enhancer
      binding protein (C/EBP), but not activating transcription factor, that was
      sensitive to both Y27632 and SB212190. The potential role of AP-1 and C/EBP in
      deformation-induced ET(B)-R expression was verified both by using decoy
      oligodeoxynucleotides mimicking the DNA-binding sites of these transcription
      factors and a nuclear run-on-based assay employing specific antibodies directed
      against AP-1 and C/EBP. Both techniques unequivocally demonstrated that
      activation of these transcription factors, namely that of C/EBP beta, contribute
      to the increase of ET(B)-R gene expression in response to cyclic stretch.

PMID- 11457850
TI  - NMR spectroscopic analysis of the first two steps of the pentose-phosphate
      pathway elucidates the role of 6-phosphogluconolactonase.
AB  - The pentose-phosphate pathway provides reductive power and nucleotide precursors
      to the cell through oxidative and nonoxidative branches, respectively. 6
      Phosphogluconolactonase is the second enzyme of the oxidative branch and
      catalyzes the hydrolysis of 6-phosphogluconolactones, the products of glucose 6
      phosphate oxidation by glucose-6-phosphate dehydrogenase. The role of 6
      phosphogluconolactonase was still questionable, because 6-phosphogluconolactones
      were believed to undergo rapid spontaneous hydrolysis. In this work, nuclear
      magnetic resonance spectroscopy was used to characterize the chemical scheme and
      kinetic features of the oxidative branch. We show that 6-phosphogluconolactones
      have in fact a nonnegligible lifetime and are highly electrophilic compounds. The
      delta form (1-5) of the lactone is the only product of glucose 6-phosphate
      oxidation. Subsequently, it leads to the gamma form (1-4) by intramolecular
      rearrangement. However, only the delta form undergoes spontaneous hydrolysis, the
      gamma form being a "dead end" of this branch. The delta form is the only
      substrate for 6-phosphogluconolactonase. Therefore, 6-phosphogluconolactonase
      activity accelerates hydrolysis of the delta form, thus preventing its conversion
      into the gamma form. Furthermore, 6-phosphogluconolactonase guards against the
      accumulation of delta-6-phosphogluconolactone, which may be toxic through its
      reaction with endogenous cellular nucleophiles. Finally, the difference between
      activity of human, Trypanosoma brucei, and Plasmodium falciparum 6
      phosphogluconolactonases is reported and discussed.

PMID- 11457851
TI  - Zn2+ and H+ are coactivators of acid-sensing ion channels.
AB  - Acid-sensing ion channels (ASICs) are cationic channels activated by
      extracellular protons. They are expressed in sensory neurons, where they are
      thought to be involved in pain perception associated with tissue acidosis. They
      are also expressed in brain. A number of brain regions, like the hippocampus,
      contain large amounts of chelatable vesicular Zn(2+). This paper shows that
      Zn(2+) potentiates the acid activation of homomeric and heteromeric ASIC2a
      containing channels (i.e. ASIC2a, ASIC1a+2a, ASIC2a+3), but not of homomeric
      ASIC1a and ASIC3. The EC(50) for Zn(2+) potentiation is 120 and 111 microm for
      the ASIC2a and ASIC1a+2a current, respectively. Zn(2+) shifts the pH dependence
      of activation of the ASIC1a+2a current from a pH(0.5) of 5.5 to 6.0. Systematic
      mutagenesis of the 10 extracellular histidines of ASIC2a leads to the
      identification of two residues (His-162 and His-339) that are essential for the
      Zn(2+) potentiating effect. Mutation of another histidine residue, His-72,
      abolishes the pH sensitivity of ASIC2a. This residue, which is located just after
      the first transmembrane domain, seems to be an essential component of the
      extracellular pH sensor of ASIC2a.

PMID- 11457852
TI  - The three-dimensional structure of the C-terminal DNA-binding domain of human
      Ku70.
AB  - The proteins Ku70 (69.8 kDa) and Ku80 (82.7 kDa) form a heterodimeric complex
      that is an essential component of the nonhomologous end joining DNA double-strand
      break repair pathway in mammalian cells. Interaction of Ku with DNA is central
      for the functions of Ku. Ku70, which is mainly responsible for the DNA binding
      activity of the Ku heterodimer, contains two DNA-binding domains. We have solved
      the solution structure of the Ku80-independent DNA-binding domain of Ku70
      encompassing residues 536-609 using nuclear magnetic resonance spectroscopy.
      Residues 536-560 are highly flexible and have a random structure but form
      specific interactions with DNA. Residues 561-609 of Ku70 form a well defined
      structure with 3 alpha-helices and also interact with DNA. The three-dimensional
      structure indicates that all conserved hydrophobic residues are in the
      hydrophobic core and therefore may be important for structural integrity. Most of
      the conserved positively charged residues are likely to be critical for DNA
      recognition. The C-terminal DNA-binding domain of Ku70 contains a helix-extended
      strand-helix motif, which occurs in other nucleic acid-binding proteins and may
      represent a common nucleic acid binding motif.

PMID- 11457853
TI  - The unique proline of the Prochlorothrix hollandica plastocyanin hydrophobic
      patch impairs electron transfer to photosystem I.
AB  - A number of surface residues of plastocyanin from Prochlorothrix hollandica have
      been modified by site-directed mutagenesis. Changes have been made in amino acids
      located in the amino-terminal hydrophobic patch of the copper protein, which
      presents a variant structure as compared with other plastocyanins. The single
      mutants Y12G, Y12F, Y12W, P14L, and double mutant Y12G/P14L have been produced.
      Their reactivity toward photosystem I has been analyzed by laser flash absorption
      spectroscopy. Plots of the observed rate constant with all mutants versus
      plastocyanin concentration show a saturation profile similar to that with wild
      type plastocyanin, thus suggesting the formation of a plastocyanin-photosystem I
      transient complex. The mutations do not induce relevant changes in the
      equilibrium constant for complex formation but induce significant variations in
      the electron transfer rate constant, mainly with the two mutants at proline 14.
      Additionally, molecular dynamics calculations indicate that mutations at position
      14 yield small changes in the geometry of the copper center. The comparative
      kinetic analysis of the reactivity of plastocyanin mutants toward photosystem I
      from different organisms (plants and cyanobacteria) reveals that reversion of the
      unique proline of Prochlorothrix plastocyanin to the conserved leucine of all
      other plastocyanins at this position enhances the reactivity of the
      Prochlorothrix protein.

PMID- 11457854
TI  - Dependence of pituitary hormone secretion on the pattern of spontaneous voltage
      gated calcium influx. Cell type-specific action potential secretion coupling.
AB  - In excitable cells, voltage-gated calcium influx provides an effective mechanism
      for the activation of exocytosis. In this study, we demonstrate that although rat
      anterior pituitary lactotrophs, somatotrophs, and gonadotrophs exhibited
      spontaneous and extracellular calcium-dependent electrical activity, voltage
      gated calcium influx triggered secretion only in lactotrophs and somatotrophs.
      The lack of action potential-driven secretion in gonadotrophs was not due to the
      proportion of spontaneously firing cells or spike frequency. Gonadotrophs
      exhibited calcium signals during prolonged depolarization comparable with signals
      observed in somatotrophs and lactotrophs. The secretory vesicles in all three
      cell types also had a similar sensitivity to voltage-gated calcium influx.
      However, the pattern of action potential calcium influx differed among three cell
      types. Spontaneous activity in gonadotrophs was characterized by high amplitude,
      sharp spikes that had a limited capacity to promote calcium influx, whereas
      lactotrophs and somatotrophs fired plateau-bursting action potentials that
      generated high amplitude calcium signals. Furthermore, a shift in the pattern of
      firing from sharp spikes to plateau-like spikes in gonadotrophs triggered
      luteinizing hormone secretion. These results indicate that the cell type-specific
      action potential secretion coupling in pituitary cells is determined by the
      capacity of their plasma membrane oscillator to generate threshold calcium
      signals.

PMID- 11457855
TI  - Caveolin-1 null mice are viable but show evidence of hyperproliferative and
      vascular abnormalities.
AB  - Caveolin-1 is the principal structural protein of caveolae membranes in
      fibroblasts and endothelia. Recently, we have shown that the human CAV-1 gene is
      localized to a suspected tumor suppressor locus, and mutations in Cav-1 have been
      implicated in human cancer. Here, we created a caveolin-1 null (CAV-1 -/-) mouse
      model, using standard homologous recombination techniques, to assess the role of
      caveolin-1 in caveolae biogenesis, endocytosis, cell proliferation, and
      endothelial nitric-oxide synthase (eNOS) signaling. Surprisingly, Cav-1 null mice
      are viable. We show that these mice lack caveolin-1 protein expression and
      plasmalemmal caveolae. In addition, analysis of cultured fibroblasts from Cav-1
      null embryos reveals the following: (i) a loss of caveolin-2 protein expression;
      (ii) defects in the endocytosis of a known caveolar ligand, i.e. fluorescein
      isothiocyanate-albumin; and (iii) a hyperproliferative phenotype. Importantly,
      these phenotypic changes are reversed by recombinant expression of the caveolin-1
      cDNA. Furthermore, examination of the lung parenchyma (an endothelial-rich
      tissue) shows hypercellularity with thickened alveolar septa and an increase in
      the number of vascular endothelial growth factor receptor (Flk-1)-positive
      endothelial cells. As predicted, endothelial cells from Cav-1 null mice lack
      caveolae membranes. Finally, we examined eNOS signaling by measuring the
      physiological response of aortic rings to various stimuli. Our results indicate
      that eNOS activity is up-regulated in Cav-1 null animals, and this activity can
      be blunted by using a specific NOS inhibitor, nitro-l-arginine methyl ester.
      These findings are in accordance with previous in vitro studies showing that
      caveolin-1 is an endogenous inhibitor of eNOS. Thus, caveolin-1 expression is
      required to stabilize the caveolin-2 protein product, to mediate the caveolar
      endocytosis of specific ligands, to negatively regulate the proliferation of
      certain cell types, and to provide tonic inhibition of eNOS activity in
      endothelial cells.

PMID- 11457856
TI  - Estrogen receptor (ER)-alpha, but not ER-beta, mediates regulation of the insulin
      like growth factor I gene by antiestrogens.
AB  - The importance of insulin-like growth factor I (IGF-I) on maintenance of skeletal
      integrity has been widely recognized. Although osteoblasts secrete some IGF-I,
      the liver is the primary endocrine source for IGF-I. We have studied the
      regulation of the human IGF-I promoter in the hepatocyte cell line Hep3B, and we
      have shown that the IGF-I promoter, when co-transfected in Hep3B cells together
      with an estrogen receptor (ER)-alpha expression vector, was transcriptionally
      regulated by raloxifene or raloxifene-like molecules but not by 17beta-estradiol
      and 4(OH)-tamoxifen. The induction mediated by raloxifene is antagonized by
      17beta-estradiol and mediated selectively by ER-alpha, but not by ER-beta.
      Transfer of IGF-I promoter sequences from -733 to -65 or from -375 to -65 to a
      minimal Fos promoter resulted in a comparable responsiveness to raloxifene. This
      region contains two CAAT/enhancer-binding protein sites and an activator protein
      1 site, both of which have been shown to be involved in estrogen receptor
      mediated transactivation. When the CAAT/enhancer-binding protein sites were
      mutated in a construct bearing the sequence from -375 to -65 in front of the
      minimal Fos promoter, raloxifene induction was reduced, whereas mutation of the
      other elements did not affect induction. In addition, using chimeric proteins, we
      delineated the domains of ER-alpha that confer to ER-alpha transactivation
      abilities on the IGF-I promoter that are not exhibited by ER-beta. These data
      shed new light on the mechanism of action of antiestrogens and might help
      explain, at least in part, the bone-protective effects observed for some
      antiestrogens in ovariectomized animals.

PMID- 11457857
TI  - Oxyluciferin, a luminescence product of firefly luciferase, is enzymatically
      regenerated into luciferin.
AB  - The activity regenerating luciferin from the luminescent product oxyluciferin was
      found in the protein fraction of a lantern extract from Photinus pyralis. The
      protein, luciferin-regenerating enzyme (LRE), was purified to homogeneity by
      ammonium sulfate precipitation followed by successive column chromatography on
      Ultrogel AcA34, S-Sepharose FF, Q-Sepharose FF, TSKgel super Q 5pw and TSKgel
      G3000 SW(XL). This enzyme was a single polypeptide with a molecular mass of 38
      kDa. LRE converted oxyluciferin to 2-cyano-6-hydroxybenzothiazole and
      thioglycolic acid. In the presence of d-cysteine, 2-cyano-6-hydroxybenzothiazole
      was turned over into luciferin. The same activities were detected in the extracts
      from two Japanese fireflies, Luciola cruciata and Luciola lateralis. We have
      cloned a cDNA encoding LRE from poly(A)+ RNA of the lantern of P. pyralis using
      reverse transcription-polymerase chain reaction, 5'-RACE (rapid amplification of
      cDNA ends) and 3'-RACE. The primary structure of LRE from P. pyralis deduced from
      the nucleotide sequence was shown to consist of 308 amino acids with a molecular
      weight of 33,619. The cDNA was successfully expressed under the control of the
      tac promoter in Escherichia coli.

PMID- 11457858
TI  - Function of YidC for the insertion of M13 procoat protein in Escherichia coli:
      translocation of mutants that show differences in their membrane potential
      dependence and Sec requirement.
AB  - The membrane insertion of the Sec-independent M13 Procoat protein in bacteria
      requires the membrane electrochemical potential and the integral membrane protein
      YidC. We show here that YidC is involved in the translocation but not in the
      targeting of the Procoat protein, because we found the protein was partitioned
      into the membrane in the absence of YidC. YidC can function also to promote
      membrane insertion of Procoat mutants that insert independently of the membrane
      potential, proving that the effect of YidC depletion is not due to a dissipation
      of the membrane potential. We also found that YidC is absolutely required for Sec
      dependent translocation of a long periplasmic loop of a mutant Procoat in which
      the periplasmic region has been extended from 20 to 194 residues. Furthermore,
      when Sec-dependent membrane proteins with large periplasmic domains were
      overproduced under YidC-limited conditions, we found that the exported proteins
      pro-OmpA and pre-peptidoglycan-associated lipoprotein accumulated in the
      cytoplasm. This suggests for Sec-dependent proteins that YidC functions at a late
      stage in membrane insertion, after the Sec translocase interacts with the
      translocating membrane protein. These studies are consistent with the
      understanding that YidC cooperates with the Sec translocase for membrane
      translocation and that YidC is required for clearing the protein-conducting
      channel.

PMID- 11457859
TI  - Differential binding of an SRF/NK-2/MEF2 transcription factor complex in normal
      versus neoplastic smooth muscle tissues.
AB  - The malignant potential of smooth muscle tumors correlates strongly with the
      disappearance of gamma-smooth muscle isoactin, a lineage-specific marker of
      smooth muscle development. In this paper, we identify a 36-base pair regulatory
      motif containing an AT-rich domain, CArG box, and a non-canonical NK-2
      homeodomain-binding site that has the capacity to regulate smooth muscle-specific
      gene expression in cultured intestinal smooth muscle cells. Serum-response factor
      associates with an NK-2 transcription factor via protein-protein interactions and
      binds to the core CArG box element. Our studies suggest that the NK-2
      transcription factor that associates with serum-response factor during smooth
      muscle differentiation is Nkx2-3. Myocyte-specific enhancer factor 2 binding to
      this regulatory complex was also observed but limited to uterine smooth muscle
      tissues. Smooth muscle neoplasms displayed altered transcription factor binding
      when compared with normal myometrium. Differential nuclear accessibility of serum
      response factor protein during smooth muscle differentiation and neoplastic
      transformation was also observed. Thus, we have identified a unique regulatory
      complex whose differential binding properties and nuclear accessibility are
      associated with modulating gamma-smooth muscle isoactin-specific gene expression
      in both normal and neoplastic tissues.

PMID- 11457860
TI  - Insulin-like growth factor receptor levels are regulated by cell density and by
      long term estrogen deprivation in MCF7 human breast cancer cells.
AB  - This work describes a reciprocal relationship between cell density and levels of
      insulin-like growth factor receptors (IGFR) in MCF7 human breast cancer cells,
      which adds a new dimension to the mechanism of cross-talk between estrogen and
      insulin-like growth factors in the regulation of breast cancer cell growth. The
      reduced binding of both (125)I-IGF1 and alphaIR3 anti-IGFR antibody to whole
      cells showed that IGFR are lost from the surface of MCF7 cells as cell density
      increases, and this occurred irrespective of the presence or absence of
      estradiol. Western immunoblotting further confirmed loss of type I IGFR from MCF7
      cells with increasing cell density. Long term estrogen deprivation was found to
      increase the levels of IGFR at all cell densities, such that after 96 weeks of
      estrogen deprivation, IGFR levels had become similar at the highest cell density
      in the absence of estradiol to the IGFR levels at the lowest cell density in the
      estrogen-maintained cells, and the levels of IGFR could be increased still
      further by estradiol. This overexpression of IGFR in the estrogen-deprived cells
      correlated with a reversal of response to exogenously added ligand, in that
      concentrations of insulin, IGFI, and IGFII that had stimulated growth of the
      estrogen-maintained cells became growth inhibitory to the estrogen-deprived
      cells. Blockade of the IGFIR with the alphaIR3 anti-IGFR antibody could partially
      inhibit the growth of the estrogen-deprived cells, suggesting that up-regulation
      of IGFR in these cells may contribute to the mechanism of adaptation to growth in
      steroid-deprived conditions which results in progression to estrogen independence
      of cell growth.

PMID- 11457861
TI  - Galpha i2 enhances in vivo activation of and insulin signaling to GLUT4.
AB  - Heterotrimeric G-proteins, including Galpha(i2), have been implicated in
      modulating glucose disposal and insulin signaling. This cross-talk between G
      protein-coupled and tyrosine kinase-coupled signaling pathways is a focal point
      for the study of integration of cell signaling. Herein we study the role of
      Galpha(i2) in modulating glucose transport, focusing upon linkages to insulin
      signaling. Utilizing mice harboring a transgene that directs the expression of a
      constitutively activated, GTPase-deficient mutant of Galpha(i2) (Q205L) in
      adipose tissue, skeletal muscle, and liver, we demonstrate that Galpha(i2)
      regulates the translocation of the insulin-sensitive GLUT4 glucose transporter in
      skeletal muscle and adipose tissue. The expression of Q205L Galpha(i2) increased
      glucose transport and translocation of GLUT4 to the plasma membrane in vivo in
      the absence of insulin stimulation. Adipocytes from the Q205L Galpha(i2) mice
      displayed enhanced insulin-stimulated glucose transport and GLUT4 translocation
      to the plasma membrane to levels nearly twice that of those from littermate
      controls. Phosphatidylinositol 3-kinase and Akt activities were constitutively
      activated in tissues expressing the Q205L Galpha(i2). Studies of adipocytes from
      wild-type mice displayed short term activation of phosphatidylinositol 3-kinase,
      Akt, and GLUT4 translocation in response to activation of Galpha(i2) by
      lysophosphatidic acid, a response sensitive to pertussis toxin. These data
      provide an explanation for the marked glucose tolerance of the Q205L Galpha(i2)
      mice and demonstrate a linkage between Galpha(i2) and GLUT4 translocation.

PMID- 11457862
TI  - Genomic structure and insulin-mediated repression of the aquaporin adipose
      (AQPap), adipose-specific glycerol channel.
AB  - Aquaporin adipose (AQPap) is a putative glycerol channel in adipocytes (Kishida,
      K., Kuriyama, H., Funahashi, T., Shimomura, I., Kihara, S., Ouchi, N., Nishida,
      M., Nishizawa, H., Matsuda, M., Takahashi, M., Hotta, K., Nakamura, T.,
      Yamashita, S., Tochino, Y., and Matsuzawa, Y. (2000) J. Biol. Chem. 275, 20896
      20902). In the current study, we examined the genomic structure of the mouse
      AQPap gene and its regulation by insulin. The mouse AQPap gene spanned 12
      kilobase pairs in chromosome 4 and consisted of 8 exons and 7 introns. The first
      two exons, designated exon 1 and exon 1', are alternatively spliced to common
      exon 2, and thus the AQPap gene possessed two potential promoters. The exon 1
      derived transcript is dominant in both adipose tissues and adipocytes on the
      basis of RNase protection assay and promoter analysis. The mRNA increased after
      fasting and decreased with refeeding. Insulin deficiency generated by
      streptozotocin enhanced the mRNA in adipose tissue. Insulin down-regulated AQPap
      mRNA in 3T3-L1 adipocytes. The AQPap promoter contained heptanucleotide
      sequences, TGTTTTT at -443/-437, similar to the insulin-response element
      identified previously in the promoters of insulin-repressed genes. Deletion and
      single base pair substitution analysis of the promoter revealed that these
      sequences were required for insulin-mediated repression of AQPap gene
      transcription. The phosphatidylinositol 3-kinase pathway was involved in this
      inhibition. We conclude that insulin represses the transcription of AQPap gene
      via insulin response element in its promoter. Sustained up-regulation of AQPap
      mRNA in adipose tissue in the insulin-resistant condition may disturb glucose
      homeostasis by increasing plasma glycerol.

PMID- 11457863
TI  - Helix proximity in OxlT, the oalate:formate antiporter of oxalobacter formigenes.
      Cross-linking between TM2 and TM11.
AB  - Experiments were designed to evaluate the proximity of transmembrane helices two
      (TM2) and eleven (TM11) in the tertiary structure of OxlT, the oxalate:formate
      exchange transporter of Oxalobacter formigenes. A tandem duplication of the
      Factor Xa protease cleavage site (IEGRIEGR) was inserted into the central
      cytoplasmic loop of an OxlT cysteine-less derivative in which an endogenous
      cleavage site had been eliminated by mutagenesis (R248Q). Using this host, double
      cysteine derivatives were constructed so as to pair one of seventeen positions in
      TM2 with one of four positions in TM11. Following treatment of membrane vesicles
      with Cu(II)(1,10-phenanthroline)(3), molecular iodine, or N,N'-o
      phenylenedimaleimide, samples were exposed to Factor Xa, and disulfide bond
      formation was assessed after SDS-polyacrylamide gel electrophoresis by staining
      with antibody directed against the OxlT C terminus. In the absence of disulfide
      bond formation, exposure to Factor Xa revealed the expected C-terminal 22-kDa
      fragment, a result unaffected by the presence of reductant. By contrast, after
      disulfide formation, OxlT mobility remained at 35 kDa, and appearance of the 22
      kDa fragment required addition of 200 mm dithiothreitol prior to electrophoresis.
      The four TM11 positions chosen for cysteine substitution lie on a helical face
      known to interact with substrate. Similarly, TM2 positions supporting disulfide
      trapping were also confined to a single helical face. We conclude that TM2 and
      TM11 are in close juxtaposition to one another in the tertiary structure of OxlT.

PMID- 11457864
TI  - Resolution of the human sex hormone-binding globulin dimer interface and evidence
      for two steroid-binding sites per homodimer.
AB  - Human sex hormone-binding globulin (SHBG) transports sex steroids in the blood.
      It functions as a homodimer, but there is little information about the topography
      of its dimerization domain, and its steroid binding stoichiometry is
      controversial. The prevailing assumption is that each homodimeric SHBG molecule
      contains a single steroid-binding site at the dimer interface. However,
      crystallographic analysis of the amino-terminal laminin G-like domain of human
      SHBG has shown that the dimerization and steroid-binding sites are distinct and
      that both monomers within a homodimeric complex are capable of binding steroid.
      To validate our crystallographic model of the SHBG homodimer, we have used site
      directed mutagenesis to create SHBG variants in which single amino acid
      substitutions (V89E and L122E) were introduced to produce steric clashes at
      critical positions within the proposed dimerization domain. The resulting
      dimerization-deficient SHBG variants contain a steroid-binding site with an
      affinity and specificity indistinguishable from wild-type SHBG. Moreover, when
      equalized in terms of their monomeric subunit content, dimerization-deficient and
      wild-type SHBGs have essentially identical steroid binding capacities. These data
      indicate that both subunits of the SHBG homodimer bind steroid and that
      measurements of the molar concentration of SHBG homodimer in serum samples have
      been overestimated by 2-fold.

PMID- 11457865
TI  - Identification of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in human
      DNA polymerase lambda: a possible role in base excision repair.
AB  - Base excision repair (BER) is a major repair pathway in eukaryotic cells
      responsible for repair of lesions that give rise to abasic (AP) sites in DNA.
      Pivotal to this process is the 5'-deoxyribose-5-phosphate lyase (dRP lyase)
      activity of DNA polymerase beta (Pol beta). DNA polymerase lambda (Pol lambda) is
      a recently identified eukaryotic DNA polymerase that is homologous to Pol beta.
      We show here that human Pol lambda exhibits dRP lyase, but not AP lyase, activity
      in vitro and that this activity is consistent with a beta-elimination mechanism.
      Accordingly, a single amino acid substitution (K310A) eliminated more than 90% of
      the wild-type dRP lyase activity, thus suggesting that Lys(310) of Pol lambda is
      the main nucleophile involved in the reaction. The dRP lyase activity of Pol
      lambda, in coordination with its polymerization activity, efficiently repaired
      uracil-containing DNA in an in vitro reconstituted BER reaction. These results
      suggest that Pol lambda may participate in "single-nucleotide" base excision
      repair in mammalian cells.

PMID- 11457866
TI  - Heparan sulfate proteoglycans: intricate molecules with intriguing functions.

PMID- 11457867
TI  - Molecular diversity of heparan sulfate.

PMID- 11457868
TI  - Heparan sulfate: lessons from knockout mice.

PMID- 11457869
TI  - The potential of signal transduction inhibitors for the treatment of arthritis:
      Is it all just JNK?

PMID- 11457870
TI  - New functions for the NHERF family of proteins.

PMID- 11457871
TI  - Cholangiocytes and primary biliary cirrhosis: prediction and predication.

PMID- 11457872
TI  - Progressive atrioventricular conduction defects and heart failure in mice
      expressing a mutant Csx/Nkx2.5 homeoprotein.
AB  - A DNA nonbinding mutant of the NK2 class homeoprotein Nkx2.5 dominantly inhibits
      cardiogenesis in Xenopus embryos, causing a small heart to develop or blocking
      heart formation entirely. Recently, ten heterozygous CSX/NKX2.5 homeoprotein
      mutations were identified in patients with congenital atrioventricular (AV)
      conduction defects. All four missense mutations identified in the human
      homeodomain led to markedly reduced DNA binding. To examine the effect of a DNA
      binding-impaired mutant of mouse Csx/Nkx2.5 in the embryonic heart, we generated
      transgenic mice expressing one such allele, I183P, under the beta-myosin heavy
      chain promoter. Unexpectedly, transgenic mice were born apparently normal, but
      the accumulation of Csx/Nkx2.5(I183P) mutant protein in the embryo, neonate, and
      adult myocardium resulted in progressive and profound cardiac conduction defects
      and heart failure. P-R prolongation observed at 2 weeks of age rapidly progressed
      into complete AV block as early as 4 weeks of age. Expression of connexins 40 and
      43 was dramatically decreased in the transgenic heart, which may contribute to
      the conduction defects in the transgenic mice. This transgenic mouse model may be
      useful in the study of the pathogenesis of cardiac dysfunction associated with
      CSX/NKX2.5 mutations in humans.

PMID- 11457873
TI  - Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF
      kappaB activation and alleviates myocardial ischemia/reperfusion injury.
AB  - Acute myocardial infarction (AMI) remains the leading cause of death in developed
      countries. Although reperfusion of coronary arteries reduces mortality, it is
      associated with tissue injury. Endothelial P-selectin-mediated infiltration of
      neutrophils plays a key role in reperfusion injury. However, the mechanism of the
      P-selectin induction is not known. Here we show that infarct size after
      ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A
      (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases
      in neutrophil infiltration in coronary endothelial P-selectin expression.
      Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P
      selectin induction in wild-type mice. In cultured endothelial cells, activation
      of GC-A augmented H2O2-induced P-selectin expression. Furthermore,
      ischemia/reperfusion-induced activation of NF-kappaB, a transcription factor that
      is known to promote P-selectin expression, is suppressed in GC-A-deficient mice.
      These results suggest that inhibition of GC-A alleviates ischemia/reperfusion
      injury through suppression of NF-kappaB-mediated P-selectin induction. This
      novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the
      basis for applying GC-A blockade in the clinical treatment of reperfusion injury.

PMID- 11457874
TI  - The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone
      escape phenomenon.
AB  - The kidneys "escape" from the Na-retaining effects of aldosterone when
      circulating levels of aldosterone are inappropriately elevated in the setting of
      normal or expanded extracellular fluid volume, e.g., in primary aldosteronism.
      Using a targeted proteomics approach, we screened renal protein extracts with
      rabbit polyclonal antibodies directed to each of the major Na transporters
      expressed along the nephron to determine whether escape from aldosterone-mediated
      Na retention is associated with decreased abundance of one or more of renal Na
      transporters. The analysis revealed that the renal abundance of the thiazide
      sensitive Na-Cl cotransporter (NCC) was profoundly and selectively decreased.
      None of the other apical solute-coupled Na transporters displayed decreases in
      abundance, nor were the total abundances of the three ENaC subunits significantly
      altered. Immunocytochemistry showed a strong decrease in NCC labeling in distal
      convoluted tubules of aldosterone-escape rats with no change in the cellular
      distribution of NCC. Ribonuclease protection assays (RPAs) revealed that the
      decrease in NCC protein abundance was not associated with altered NCC mRNA
      abundance. Thus, the thiazide-sensitive Na-Cl cotransporter of the distal
      convoluted tubule appears to be the chief molecular target for regulatory
      processes responsible for mineralocorticoid escape, decreasing in abundance via a
      posttranscriptional mechanism.

PMID- 11457875
TI  - Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary
      cirrhosis autoantigen, during apoptosis.
AB  - The close association between autoantibodies against pyruvate dehydrogenase-E2
      (PDC-E2), a ubiquitous mitochondrial protein, and primary biliary cirrhosis (PBC)
      is unexplained. Many autoantigens are selectively modified during apoptosis,
      which has focused attention on apoptotic cells as a potential source of "neo
      antigens" responsible for activating autoreactive lymphocytes. Since increased
      apoptosis of bile duct epithelial cells (cholangiocytes) is evident in patients
      with PBC, we evaluated the effect of apoptosis on PDC-E2. Autoantibody
      recognition of PDC-E2 by immunofluorescence persisted in apoptotic cholangiocytes
      and appeared unchanged by immunoblot analysis. PDC-E2 was neither cleaved by
      caspases nor concentrated into surface blebs in apoptotic cells. In other cell
      types, autoantibody recognition of PDC-E2, as assessed by immunofluorescence, was
      abrogated after apoptosis, although expression levels of PDC-E2 appeared
      unchanged when examined by immunoblot analysis. Both overexpression of Bcl-2 and
      depletion of glutathione before inducing apoptosis prevented this loss of
      autoantibody recognition, suggesting that glutathiolation, rather than
      degradation or loss, of PDC-E2 was responsible for the loss of immunofluorescence
      signal. We postulate that apoptotic cholangiocytes, unlike other apoptotic cell
      types, are a potential source of immunogenic PDC-E2 in patients with PBC.

PMID- 11457876
TI  - A family with complement factor D deficiency.
AB  - A complement factor D deficiency was found in a young woman who had experienced a
      serious Neisseria meningitidis infection, in a deceased family member with a
      history of meningitis, and in three relatives without a history of serious
      infections. The patient and these three relatives showed a normal activity of the
      classical complement pathway, but a very low activity of the alternative
      complement pathway and a very low capacity to opsonize Escherichia coli and N.
      meningitidis (isolated from the patient) for phagocytosis by normal human
      neutrophils. The alternative pathway-dependent hemolytic activity and the
      opsonizing capacity of these sera were restored by addition of purified factor D.
      The family had a high degree of consanguinity, and several other family members
      exhibited decreased levels of factor D. The gene encoding factor D was found to
      contain a point mutation that changed the TCG codon for serine 42 into a TAG stop
      codon. This mutation was found in both alleles of the five completely factor D
      deficient family members and in one allele of 21 other members of the same family
      who had decreased or low-normal factor D levels in their serum. The gene sequence
      of the signal peptide of human factor D was also identified. Our report is the
      first, to our knowledge, to document a Factor D gene mutation. The mode of
      inheritance of factor D deficiency is autosomal recessive, in accordance with the
      localization of the Factor D gene on chromosome 19. Increased susceptibility for
      infections in individuals with a partial factor D deficiency is unlikely.

PMID- 11457877
TI  - Iloprost suppresses connective tissue growth factor production in fibroblasts and
      in the skin of scleroderma patients.
AB  - Patients with scleroderma receiving Iloprost as a treatment for severe Raynaud's
      phenomenon report a reduction in skin tightness, suggesting that this drug
      inhibits skin fibrosis. Connective tissue growth factor (CTGF), a recently
      described profibrotic cytokine, acts downstream and in concert with TGF-beta to
      stimulate the fibrotic process and is involved in the fibrosis seen in
      scleroderma. Here we show that Iloprost, acting by elevation of cAMP, blocks the
      induction of CTGF and the increase in collagen synthesis in fibroblasts exposed
      to TGF-beta. The potency of Iloprost with respect to suppression of CTGF far
      exceeds that of other prostanoid receptor agonists, suggesting that its effect is
      mediated by the prostacyclin receptor IP. By sampling dermal interstitial fluid
      using a suction blister device, we show that CTGF levels are greatly elevated in
      the dermis of scleroderma patients compared with healthy controls and that
      Iloprost infusion causes a marked decrease in dermal CTGF levels. These studies
      suggest that Iloprost could be reducing the level of a key profibrotic cytokine
      in scleroderma patients and that endogenous production of eicosanoids may limit
      the fibrotic response to TGF-beta.

PMID- 11457878
TI  - Lymphocytes are important in early atherosclerosis.
AB  - Lymphocytes represent a potentially important proinflammatory cell that localizes
      to atherosclerotic lesions. To determine whether they contribute to lesion
      development, atherosclerosis-prone (LDLR(-/-)) mice were crossed with lymphocyte
      deficient (RAG1(-/-)) mice to generate double knockout progeny. After 8 weeks on
      a Western-type diet (WTD), lesion development was reduced by 54% in double
      knockout mice, as compared with matched LDLR(-/-) controls. However, these
      significant differences in lesion area gradually subsided as the WTD was
      continued for 12 and 16 weeks. Consistent with this observation, histological
      studies determined that lesion initiation and early progression were delayed in
      RAG1/LDL-R double knockout mice. Differences in lesion area did not correlate
      with any significant alterations in plasma lipid levels. These studies suggest
      that lymphocytes play an important role early in atherogenesis.

PMID- 11457879
TI  - Development and prevention of advanced diabetic nephropathy in RAGE
      overexpressing mice.
AB  - Vascular complications arising from multiple environmental and genetic factors
      are responsible for many of the disabilities and short life expectancy associated
      with diabetes mellitus. Here we provide the first direct in vivo evidence that
      interactions between advanced glycation end products (AGEs; nonenzymatically
      glycosylated protein derivatives formed during prolonged hyperglycemic exposure)
      and their receptor, RAGE, lead to diabetic vascular derangement. We created
      transgenic mice that overexpress human RAGE in vascular cells and crossbred them
      with another transgenic line that develops insulin-dependent diabetes shortly
      after birth. The resultant double transgenic mice exhibited increased hemoglobin
      A(1c) and serum AGE levels, as did the diabetic controls. The double transgenic
      mice demonstrated enlargement of the kidney, glomerular hypertrophy, increased
      albuminuria, mesangial expansion, advanced glomerulosclerosis, and increased
      serum creatinine compared with diabetic littermates lacking the RAGE transgene.
      To our knowledge, the development of this double transgenic mouse provides the
      first animal model that exhibits the renal changes seen in humans. Furthermore,
      the phenotypes of advanced diabetic nephropathy were prevented by administering
      an AGE inhibitor, (+/-)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5
      ylacetanilide (OPB-9195), thus establishing the AGE-RAGE system as a promising
      target for overcoming this aspect of diabetic pathogenesis.

PMID- 11457880
TI  - Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell
      hybridoma.
AB  - The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is
      blocked by pertussis toxin, suggesting the involvement of a chemokine. To study
      whether this chemokine is SDF-1, we employed a strategy proposed previously for
      gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for
      HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell
      surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell
      hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and
      prevents the latter protein from reaching the surface. These cells failed to
      migrate toward SDF-1 or to invade fibroblast monolayers, although they could
      still migrate toward thymus and activation-regulated chemokine (TARC) and invade
      TARC-treated monolayers. Furthermore, the ability of the transfected cells to
      disseminate to multiple organs upon intravenous injection into mice was
      abolished. This dissemination reflects the in vivo migration patterns of
      activated and memory T cells into nonhematopoietic tissues, which is thus likely
      to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may
      affect this migration with consequences for T cell function. Our results also
      suggest a decisive role for CXCR4 in the dissemination of hematopoietic
      malignancies expressing this receptor.

PMID- 11457881
TI  - Effects of inhaled nitric oxide on regional blood flow are consistent with
      intravascular nitric oxide delivery.
AB  - Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating
      thiol-containing plasma molecules, or by conversion to nitrite, all reactions
      potentially preserving its bioactivity in blood. Here we examined the
      contribution of blood-transported NO to regional vascular tone in humans before
      and during NO inhalation. While breathing room air and then room air with NO at
      80 parts per million, forearm blood flow was measured in 16 subjects at rest and
      after blockade of forearm NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA)
      followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and
      increased resistance by 50%, an effect that was blocked by NO inhalation. With NO
      inhalation, resistance was significantly lower during L-NMMA infusion, both at
      rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S
      nitrosothiols did not change with NO inhalation. Arterial nitrite levels
      increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold
      to the micromolar range, and both measures were consistently higher in the
      arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar
      range, with no significant artery-to-vein gradients. These results indicate that
      inhaled NO during blockade of regional NO synthesis can supply intravascular NO
      to maintain normal vascular function. This effect may have application for the
      treatment of diseases characterized by endothelial dysfunction.

PMID- 11457882
TI  - Loss of glomerular foot processes is associated with uncoupling of podocalyxin
      from the actin cytoskeleton.
AB  - Podocalyxin (PC), the major sialoprotein of glomerular epithelial cells (GECs),
      helps maintain the characteristic architecture of the foot processes and the
      patency of the filtration slits. PC associates with actin via ezrin, a member of
      the ERM family of cytoskeletal linker proteins. Here we show that PC is linked to
      ezrin and the actin cytoskeleton via Na(+)/H(+)-exchanger regulatory factor 2
      (NHERF2), a scaffold protein containing two PDZ (PSD-95/Dlg/ZO-1) domains and an
      ERM-binding region. The cytoplasmic tail of PC contains a C-terminal PDZ-binding
      motif (DTHL) that binds to the second PDZ domain of NHERF2 in yeast two-hybrid
      and in vitro pull-down assays. By immunocytochemistry NHERF2 colocalizes with PC
      and ezrin along the apical domain of the GEC plasma membrane. NHERF2 and ezrin
      form a multimeric complex with PC, as they coimmunoprecipitate with PC. The
      PC/NHERF2/ezrin complex interacts with the actin cytoskeleton, and this
      interaction is disrupted in GECs from puromycin aminonucleoside-, protamine
      sulfate-, or sialidase-treated rats, which show a dramatic loss of foot
      processes, comparable to that seen in the nephrotic syndrome. Thus NHERF2 appears
      to function as a scaffold protein linking PC to ezrin and the actin cytoskeleton.
      PC/NHERF2/ezrin/actin interactions are disrupted in pathologic conditions
      associated with changes in GEC foot processes, indicating their importance for
      maintaining the unique organization of this epithelium.

PMID- 11457883
TI  - ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary
      cholesterol excretion in transgenic mice.
AB  - The discovery of the ABCA1 lipid transporter has generated interest in modulating
      human plasma HDL levels and atherogenic risk by enhancing ABCA1 gene expression.
      To determine if increased ABCA1 expression modulates HDL metabolism in vivo, we
      generated transgenic mice that overexpress human ABCA1 (hABCA1-Tg). Hepatic and
      macrophage expression of hABCA1 enhanced macrophage cholesterol efflux to apoA-I;
      increased plasma cholesterol, cholesteryl esters (CEs), free cholesterol,
      phospholipids, HDL cholesterol, and apoA-I and apoB levels; and led to the
      accumulation of apoE-rich HDL1. ABCA1 transgene expression delayed 125I-apoA-I
      catabolism in both liver and kidney, leading to increased plasma apoA-I levels,
      but had no effect on apoB secretion after infusion of Triton WR1339. Although the
      plasma clearance of HDL-CE was not significantly altered in hABCA1-Tg mice, the
      net hepatic delivery of exogenous 3H-CEt-HDL, which is dependent on the HDL pool
      size, was increased 1.5-fold. In addition, the cholesterol and phospholipid
      concentrations in hABCA1-Tg bile were increased 1.8-fold. These studies show that
      steady-state overexpression of ABCA1 in vivo (a) raises plasma apoB levels
      without altering apoB secretion and (b) raises plasma HDL-C and apoA-I levels,
      facilitating hepatic reverse cholesterol transport and biliary cholesterol
      excretion. Similar metabolic changes may modify atherogenic risk in humans.

PMID- 11457884
TI  - A virus-induced molecular mimicry model of multiple sclerosis.
AB  - Molecular mimicry is the process by which virus infection activates T cells that
      are cross-reactive with self antigens. Infection of SJL/J mice with the
      neurotropic picornavirus Theiler's murine encephalomyelitis virus (TMEV) leads to
      a progressive CD4(+) T cell-mediated demyelinating disease similar to multiple
      sclerosis. To study the potential of virus-induced molecular mimicry to initiate
      autoimmune demyelination, a nonpathogenic TMEV variant was engineered to encode a
      30-mer peptide encompassing the immunodominant encephalitogenic myelin
      proteolipid protein (PLP139-151) epitope. Infection with the PLP139-151-encoding
      TMEV led within 10-14 days to a rapid-onset paralytic demyelinating disease
      characterized by PLP139-151-specific CD4(+) Th1 responses; insertion of a non
      self ovalbumin sequence led to restoration of the normal late-onset disease.
      Early-onset disease was also observed in mice infected with a TMEV encoding
      PLP139-151 with an amino acid substitution at the secondary T cell receptor (TCR)
      contact residue (H147A), but not in mice infected with TMEV encoding a PLP139-151
      substitution at the primary TCR contact (W144A). Most significantly, mice
      infected with TMEV encoding a Haemophilus influenzae mimic peptide, sharing only
      6 of 13 amino acids with PLP139-151, displayed rapid-onset disease and developed
      cross-reactive PLP139-151-specific CD4(+) Th1 responses. To our knowledge, this
      is the first study showing that a naturally infectious virus encoding a myelin
      epitope mimic can directly initiate organ-specific T cell-mediated autoimmunity.

PMID- 11457885
TI  - Development of diabetes mellitus in aging transgenic mice following suppression
      of pancreatic homeoprotein IDX-1.
AB  - Monogenic forms of diabetes can result from mutations in genes encoding
      transcription factors. Mutations in the homeodomain transcription factor IDX-1, a
      critical regulator of pancreas development and insulin gene transcription, confer
      a strong predisposition to the development of diabetes mellitus in humans. To
      investigate the role of IDX-1 expression in the pathogenesis of diabetes, we
      developed a model for the inducible impairment of IDX-1 expression in pancreatic
      beta cells in vivo by engineering an antisense ribozyme specific for mouse IDX-1
      mRNA under control of the reverse tetracycline transactivator (rtTA). Doxycycline
      induced impairment of IDX-1 expression reduced activation of the Insulin promoter
      but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate
      IDX-1 transcription to maintain IDX-1 levels within a narrow range. In transgenic
      mice that express both rtTA and the antisense ribozyme construct, impaired IDX-1
      expression elevated glycated hemoglobin levels, diminished glucose tolerance, and
      decreased insulin/glucose ratios. Metabolic phenotypes induced by IDX-1
      deficiency were observed predominantly in male mice over 18 months of age,
      suggesting that cellular mechanisms to protect IDX-1 levels in pancreatic beta
      cells decline with aging. We propose that even in the absence of Idx-1 gene
      mutations, pathophysiological processes that decrease IDX-1 levels are likely to
      impair glucose tolerance. Therapeutic strategies to attain normal glucose
      homeostasis by restoring normal IDX-1 levels may be of particular importance for
      older individuals with diabetes mellitus.

PMID- 11457886
TI  - Constitutively activated Akt-1 is vital for the survival of human monocyte
      differentiated macrophages. Role of Mcl-1, independent of nuclear factor (NF)
      kappaB, Bad, or caspase activation.
AB  - Recent data from mice deficient for phosphatase and tensin homologue deleted from
      chromosome 10 or src homology 2 domain-containing 5' inositol phosphatase,
      phosphatases that negatively regulate the phosphatidylinositol 3-kinase (PI3K)
      pathway, revealed an increased number of macrophages in these animals, suggesting
      an essential role for the PI3K pathway for macro-phage survival. Here, we focused
      on the role of the PI3K-regulated serine/threonine kinase Akt-1 in modulating
      macrophage survival. Akt-1 was constitutively activated in human macrophages and
      addition of the PI3K inhibitor, LY294002, suppressed the activation of Akt-1 and
      induced cell death. Furthermore, suppression of Akt-1 by inhibition of PI3K or a
      dominant negative (DN) Akt-1 resulted in loss of mitochondrial transmembrane
      potential, activation of caspases-9 and -3, and DNA fragmentation. The effects of
      PI3K inhibition were reversed by the ectopic expression of constitutively
      activated Akt-1 or Bcl-x(L). Inhibition of PI3K/Akt-1 pathway either by LY294002
      or DN Akt-1 had no effect on the constitutive or inducible activation of nuclear
      factor (NF)-kappaB in human macrophages. However, after inhibition of the
      PI3K/Akt-1 pathway, a marked decrease in the expression of the antiapoptotic
      molecule Mcl-1, but not other Bcl-2 family members was observed, and Mcl-1
      rescued macrophages from LY294002-induced cell death. Further, inhibition of Mcl
      1 by antisense oligonucleotides, also resulted in macrophage apoptosis. Thus, our
      findings demonstrate that the constitutive activation of Akt-1 regulates
      macrophage survival through Mcl-1, which is independent of caspases, NF-kappaB,
      or Bad.

PMID- 11457887
TI  - Mapping precursor movement through the postnatal thymus reveals specific
      microenvironments supporting defined stages of early lymphoid development.
AB  - Cellular differentiation is a complex process involving integrated signals for
      lineage specification, proliferation, endowment of functional capacity, and
      survival or cell death. During embryogenesis, spatially discrete environments
      regulating these processes are established during the growth of tissue mass, a
      process that also results in temporal separation of developmental events. In
      tissues that undergo steady-state postnatal differentiation, another means for
      inducing spatial and temporal separation of developmental cues must be
      established. Here we show that in the postnatal thymus, this is achieved by
      inducing blood-borne precursors to enter the organ in a narrow region of the
      perimedullary cortex, followed by outward migration across the cortex before
      accumulation in the subcapsular zone. Notably, blood precursors do not
      transmigrate the cortex in an undifferentiated state, but rather undergo
      progressive developmental changes during this process, such that defined
      precursor stages appear in distinct cortical regions. Identification of these
      cortical regions, together with existing knowledge regarding the genetic
      potential of the corresponding lymphoid precursors, sets operational boundaries
      for stromal environments that are likely to induce these differentiative events.
      We conclude that active cell migration between morphologically similar but
      functionally distinct stromal regions is an integral component regulating
      differentiation and homeostasis in the steady-state thymus.

PMID- 11457888
TI  - Knock-in mutation of the distal four tyrosines of linker for activation of T
      cells blocks murine T cell development.
AB  - The integral membrane adapter protein linker for activation of T cells (LAT)
      performs a critical function in T cell antigen receptor (TCR) signal transduction
      by coupling the TCR to downstream signaling pathways. After TCR engagement, LAT
      is tyrosine phosphorylated by ZAP-70 creating docking sites for multiple src
      homology 2-containing effector proteins. In the Jurkat T cell line, the distal
      four tyrosines of LAT bind PLCgamma-1, Grb2, and Gads. Mutation of these four
      tyrosine residues to phenylalanine (4YF) blocked TCR-mediated calcium
      mobilization, Erk activation, and nuclear factor (NF)-AT activation. In this
      study, we examined whether these four tyrosine residues were essential for T cell
      development by generating LAT "knock-in" mutant mice that express the 4YF mutant
      protein under the control of endogenous LAT regulatory sequences. Significantly,
      the phenotype of 4YF knock-in mice was identical to LAT(-/)- (null) mice;
      thymocyte development was arrested at the immature CD4(-)CD8(-) stage and no
      mature T cells were present. Knock-in mice expressing wild-type LAT protein,
      generated by a similar strategy, displayed a normal T cell developmental profile.
      These results demonstrate that the distal four tyrosine residues of LAT are
      essential for preTCR signaling and T cell development in vivo.

PMID- 11457889
TI  - Regulation of interleukin (IL)-18 receptor alpha chain expression on CD4(+) T
      cells during T helper (Th)1/Th2 differentiation. Critical downregulatory role of
      IL-4.
AB  - Interleukin (IL)-18 has been well characterized as a costimulatory factor for the
      induction of IL-12-mediated interferon (IFN)-gamma production by T helper (Th)1
      cells, but also can induce IL-4 production and thus facilitate the
      differentiation of Th2 cells. To determine the mechanisms by which IL-18 might
      regulate these diametrically distinct immune responses, we have analyzed the role
      of cytokines in the regulation of IL-18 receptor alpha chain (IL-18Ralpha)
      expression. The majority of peripheral CD4(+) T cells constitutively expressed
      the IL-18Ralpha. Upon antigen stimulation in the presence of IL-12, marked
      enhancement of IL-18Ralpha expression was observed. IL-12-mediated upregulation
      of IL-18Ralpha required IFN-gamma. Activated CD4(+) T cells that expressed low
      levels of IL-18Ralpha could produce IFN-gamma when stimulated with the
      combination of IL-12 and IL-18, while CD4(+) cells which expressed high levels of
      IL-18Ralpha could respond to IL-18 alone. In contrast, T cell stimulation in the
      presence of IL-4 resulted in a downregulation of IL-18Ralpha expression. Both IL
      4(-/)- and signal transducer and activator of transcription (Stat)6(-/)- T cells
      expressed higher levels of IL-18Ralpha after TCR stimulation. Furthermore,
      activated T cells from Stat6(-/)- mice produced more IFN-gamma in response to IL
      18 than wild-type controls. Thus, positive/negative regulation of the IL-18Ralpha
      by the major inductive cytokines (IL-12 and IL-4) determines the capacity of IL
      18 to polarize an immune response.

PMID- 11457890
TI  - Fas ligand triggers pulmonary silicosis.
AB  - We investigated the role of Fas ligand in murine silicosis. Wild-type mice
      instilled with silica developed severe pulmonary inflammation, with local
      production of tumor necrosis factor (TNF)-alpha, and interstitial neutrophil and
      macrophage infiltration in the lungs. Strikingly, Fas ligand-deficient
      generalized lymphoproliferative disease mutant (gld) mice did not develop
      silicosis. The gld mice had markedly reduced neutrophil extravasation into
      bronchoalveolar space, and did not show increased TNF-alpha production, nor
      pulmonary inflammation. Bone marrow chimeras and local adoptive transfer
      demonstrated that wild-type, but not Fas ligand-deficient lung macrophages
      recruit neutrophils and initiate silicosis. Silica induced Fas ligand expression
      in lung macrophages in vitro and in vivo, and promoted Fas ligand-dependent
      macrophage apoptosis. Administration of neutralizing anti-Fas ligand antibody in
      vivo blocked induction of silicosis. Thus, Fas ligand plays a central role in
      induction of pulmonary silicosis.

PMID- 11457891
TI  - Interferon gamma stabilizes the T helper cell type 1 phenotype.
AB  - T helper cell (Th)1-primed CD4 T cells from wild-type donors make little
      interleukin (IL)-4 when restimulated under Th2 conditions. However, such
      restimulation of Th1-primed cells from interferon (IFN)-gamma(2/-) or IFN-gamma
      receptor (IFN-gammaR)(-/-) mice resulted in substantial production of IL-4 and
      other Th2 cytokines. Adding IFN-gamma to the priming culture markedly diminished
      the capacity of Th1-primed IFN-gamma(2/-) cells to express IL-4. Even IFN-gamma
      producing cells from IFN-gammaR(-/-) mice could acquire IL-4-producing capacity.
      Thus, IFN-gamma is not required for the development of IFN-gamma-producing
      capacity, but it plays a critical role in suppressing the IL-4-producing
      potential of Th1 cells.

PMID- 11457892
TI  - Swift development of protective effector functions in naive CD8(+) T cells
      against malaria liver stages.
AB  - We generated T cell receptor transgenic mice specific for the liver stages of the
      rodent malaria parasite Plasmodium yoelii and studied the early events in the
      development of in vivo effector functions in antigen-specific CD8(+) T cells.
      Differently to activated/memory cells, naive CD8(+) T cells are not capable of
      exerting antiparasitic activity unless previously primed by parasite
      immunization. While naive cells need to differentiate before achieving effector
      status, the time required for this process is very short. Indeed, interferon
      (IFN)-gamma and perforin mRNA are detectable 24 h after immunization and IFN
      gamma secretion and cytotoxic activity are detected ex vivo 24 and 48 h after
      immunization, respectively. In contrast, the proliferation of CD8(+) T cells
      begins after 24 h and an increase in the total number of antigen-specific cells
      is detected only after 48 h. Remarkably, a strong CD8(+) T cell-mediated
      inhibition of parasite development is observed in mice challenged with viable
      parasites only 24 h after immunization with attenuated parasites. These results
      indicate that differentiation of naive CD8(+) T cells does not begin only after
      extensive cell division, rather this process precedes or occurs simultaneously
      with proliferation.

PMID- 11457893
TI  - Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible
      genes with essential, pathogen-specific roles in resistance to infection.
AB  - The cytokine interferon (IFN)-gamma regulates immune clearance of parasitic,
      bacterial, and viral infections; however, the underlying mechanisms are poorly
      understood. Recently, a family of IFN-gamma-induced genes has been identified
      that encode 48-kD GTP-binding proteins that localize to the endoplasmic reticulum
      of cells. The prototype of this family, IGTP, has been shown to be required for
      host defense against acute infections with the protozoan parasite Toxoplasma
      gondii, but not for normal clearance of the bacterium Listeria monocytogenes and
      murine cytomegalovirus (MCMV). To determine whether other members of the gene
      family also play important roles in immune defense, we generated mice that lacked
      expression of the genes LRG-47 and IRG-47, and examined their responses to
      representative pathogens. After infection with T. gondii, LRG-47-deficient mice
      succumbed uniformly and rapidly during the acute phase of the infection; in
      contrast, IRG-47-deficient mice displayed only partially decreased resistance
      that was not manifested until the chronic phase. After infection with L.
      monocytogenes, LRG-47-deficient mice exhibited a profound loss of resistance,
      whereas IRG-47-deficient mice exhibited completely normal resistance. In
      addition, both strains displayed normal clearance of MCMV. Thus, LRG-47 and IRG
      47 have vital, but distinct roles in immune defense against protozoan and
      bacterial infections.

PMID- 11457894
TI  - Defective gp130-mediated signal transducer and activator of transcription (STAT)
      signaling results in degenerative joint disease, gastrointestinal ulceration, and
      failure of uterine implantation.
AB  - The receptor subunit gp130 transduces multiple cell type-specific activities of
      the leukemia inhibitory factor (LIF)/interleukin (IL)-6 family of cytokines
      through the signal transducer and activator of transcription (STAT) and src
      homology 2 domain-bearing protein tyrosine phosphatase (SHP)-2/ras/Erk pathways.
      To define STAT-dependent physiological responses, we generated mice with a COOH
      terminal gp130(DeltaSTAT) "knock-in" mutation which deleted all STAT-binding
      sites. gp130(DeltaSTAT) mice phenocopyed mice deficient for IL-6 (impaired
      humoral and mucosal immune and hepatic acute phase responses) and LIF (failure of
      blastocyst implantation). However, unlike mice with null mutations in any of the
      components in the gp130 signaling pathway, gp130(DeltaSTAT) mice also displayed
      gastrointestinal ulceration and a severe joint disease with features of chronic
      synovitis, cartilaginous metaplasia, and degradation of the articular cartilage.
      Mitogenic hyperresponsiveness of synovial cells to the LIF/IL-6 family of cyto
      kines was caused by sustained gp130-mediated SHP-2/ras/Erk activation due to
      impaired STAT-mediated induction of suppressor of cytokine signaling (SOCS)
      proteins which normally limits gp130 signaling. Therefore, the joint pathology in
      gp130(DeltaSTAT) mice is likely to arise from the disturbance of the otherwise
      balanced activation of the SHP-2/ras/Erk and STAT signaling cascades emanating
      from gp130.

PMID- 11457895
TI  - Importance of primary capture and L-selectin-dependent secondary capture in
      leukocyte accumulation in inflammation and atherosclerosis in vivo.
AB  - In the multistep process of leukocyte extravasation, the mechanisms by which
      leukocytes establish the initial contact with the endothelium are unclear. In
      parallel, there is a controversy regarding the role for L-selectin in leukocyte
      recruitment. Here, using intravital microscopy in the mouse, we investigated
      leukocyte capture from the free flow directly to the endothelium (primary
      capture), and capture mediated through interactions with rolling leukocytes
      (secondary capture) in venules, in cytokine-stimulated arterial vessels, and on
      atherosclerotic lesions in the aorta. Capture was more prominent in arterial
      vessels compared with venules. In venules, the incidence of capture increased
      with increasing vessel diameter and wall shear rate. Secondary capture required a
      minimum rolling leukocyte flux and contributed by approximately 20-50% of total
      capture in all studied vessel types. In arteries, secondary capture induced
      formation of clusters and strings of rolling leukocytes. Function inhibition of L
      selectin blocked secondary capture and thereby decreased the flux of rolling
      leukocytes in arterial vessels and in large (>45 microm in diameter), but not
      small (<45 microm), venules. These findings demonstrate the importance of
      leukocyte capture from the free flow in vivo. The different impact of blockage of
      secondary capture in venules of distinct diameter range, rolling flux, and wall
      shear rate provides explanations for the controversy regarding the role of L
      selectin in various situations of leukocyte recruitment. What is more, secondary
      capture occurs on atherosclerotic lesions, a fact that provides the first
      evidence for roles of L-selectin in leukocyte accumulation in atherogenesis.

PMID- 11457896
TI  - The use of lymphocyte function-associated antigen (LFA)-1-deficient mice to
      determine the role of LFA-1, Mac-1, and alpha4 integrin in the inflammatory
      response of neutrophils.
AB  - After injury or infection, neutrophils rapidly migrate from the circulation into
      tissues by means of an orderly progression of adhesion receptor engagements.
      Neutrophils have been previously considered to use selectins exclusively to roll
      on vessels before an adhesion step mediated by the beta2 integrins, lymphocyte
      function-associated antigen (LFA)-1, and Mac-1. Here we use LFA-1(-/-) mice,
      function blocking monoclonal antibodies, and intravital microscopy to investigate
      the roles of LFA-1, Mac-1, and alpha4 integrins in neutrophil recruitment in
      vivo. For the first time, we show that LFA-1 makes a contribution to neutrophil
      rolling by stabilizing the transient attachment or tethering phase of rolling. In
      contrast, Mac-1 does not appear to be important for either rolling or firm
      adhesion, but instead contributes to emigration from the vessel. Blocking Mac-1
      in the presence of LFA-1 significantly reduces emigration, suggesting cooperation
      between these two integrins. Low levels of alpha4beta1 integrin can be detected
      on neutrophils from LFA-1(+/+) and (-/-) mice. These cells make use of
      alpha4beta1 during the rolling phase, particularly in the absence of LFA-1. Thus
      LFA-1 and alpha4beta1, together with the selectins, are involved in the rolling
      phase of neutrophil recruitment, and, in turn, affect the later stages of the
      transmigration event.

PMID- 11457897
TI  - Increased severity of local and systemic anaphylactic reactions in gp49B1
      deficient mice.
AB  - gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits
      FcstraightepsilonRI-induced mast cell activation when the two receptors are
      coligated with antibodies in vitro. The critical question of in vivo function of
      gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a
      significantly increased sensitivity to IgE-dependent passive cutaneous
      anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in
      situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a
      lower threshold for antigen challenge in active cutaneous anaphylaxis, in which
      the antigen-specific antibody levels were comparable in gp49B1-deficient and
      sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly
      greater and faster death rate in active systemic anaphylaxis. These results
      indicate that gp49B1 innately dampens adaptive immediate hypersensitivity
      responses by suppressing mast cell activation in vivo. In addition, this study
      provides a new concept and target for regulation of allergic disease
      susceptibility and severity.

PMID- 11457898
TI  - Sink regulation of photosynthesis.
AB  - The concept that photosynthetic flux is influenced by the accumulation of photo
      assimilate persisted for 100 years before receiving any strong experimental
      support. Precise analysis of the mechanisms of photosynthetic responses to sink
      activity required the development of a battery of appropriate molecular
      techniques and has benefited from contemporary interest in the effects of
      elevated CO2 on photosynthesis. Photosynthesis is one of the most highly
      integrated and regulated metabolic processes to maximize the use of available
      light, to minimize the damaging effects of excess light and to optimize the use
      of limiting carbon and nitrogen resources. Hypotheses of feedback regulation must
      take account of this integration. In the short term, departure from homeostasis
      can lead to redox signals, which cause rapid changes in the transcription of
      genes encoding photosystems I and II. End-product synthesis can exert short-term
      metabolic feedback control through Pi recycling. Beyond this, carbohydrate
      accumulation in leaves when there is an imbalance between source and sink at the
      whole plant level can lead to decreased expression of photosynthetic genes and
      accelerated leaf senescence. In a high CO2 world this may become a more prevalent
      feature of photosynthetic regulation. However, sink regulation of photosynthesis
      is highly dependent on the physiology of the rest of the plant. This
      physiological state regulates photosynthesis through signal transduction pathways
      that co-ordinate the plant carbon : nitrogen balance, which match photosynthetic
      capacity to growth and storage capacity and underpin and can override the direct
      short-term controls of photosynthesis by light and CO2. Photosynthate supply and
      phytohormones, particularly cytokinins, interact with nitrogen supply to control
      the expression of photosynthesis genes, the development of leaves and the whole
      plant nitrogen distribution, which provides the dominant basis for sink
      regulation of photosynthesis.

PMID- 11457899
TI  - Water deficit inhibits cell division and expression of transcripts involved in
      cell proliferation and endoreduplication in maize endosperm.
AB  - Water deficit at the early post-pollination stage in cereal grains decreases
      endosperm cell division and, in turn, decreases the capacity for storage material
      accumulation. Post-mitotic replication of nuclear DNA (endoreduplication) may
      also play a role in stress effects. To gain a better understanding of the extent
      to which cell proliferation and endoreduplication are affected by water deficit,
      nuclear numbers and size were examined in endosperms of maize (Zea mays L.) by
      flow cytometry and the transcript levels of genes which have recognized roles in
      the cell cycle were quantified. Water deficit from 5-13 d after pollination (DAP)
      decreased the rate of endosperm cell division by 90% and inhibited [3H]-thymidine
      incorporation into DNA from 9-13 DAP. The proportion of nuclei engaging in
      endoreduplication and nuclear DNA content increased steadily from 9-13 DAP in
      controls, but water deficit initially increased the proportion of
      endoreduplicating nuclei at 9 DAP, then halted further entry into
      endoreduplication and S-phase cycling from 9-13 DAP. Transcript levels of alpha
      tubulin, and the S-phase gene products histone H3 and PCNA were not affected by
      water deficit until 13 DAP, whereas those of ZmCdc2, a cyclin dependent kinase
      (CDK) with regulatory roles in mitosis, were inhibited substantially from 9-13
      DAP. Cell proliferation and associated processes were inhibited at initial stages
      of the stress episode, whereas endoreduplication and associated S-phase processes
      were not inhibited until the stress was more advanced. It was concluded that
      endosperm mitosis has greater sensitivity than endoreduplication to water
      deficit.

PMID- 11457900
TI  - Brefeldin A affects adhesion of zoospores of the green alga Enteromorpha.
AB  - Primary adhesion of zoospores of the green macroalga Enteromorpha to substrata
      involves a massive release of adhesive glycoproteins from Golgi-derived, membrane
      bounded vesicles in the anterior region of the spore, followed by rapid curing.
      This process is sensitive to low concentrations (5-10 microg x ml(-1)) of the
      secretion-inhibiting antibiotic, brefeldin A (BFA). The proportion of cells that
      settled in BFA was reduced by approximately 50%, but the effect was fully
      reversed by washing in seawater to remove the BFA. Ultrastructural observations
      showed that BFA caused the breakdown of Golgi stacks in the majority of cells
      examined. When settled cells were subjected to shear stress, a greater proportion
      of those settled in the presence of BFA were detached, compared with controls,
      indicating reduced adhesion strength in the presence of the antibiotic. The most
      likely reason for this is that strong adhesion to substrata either requires the
      synthesis of extra adhesive materials beyond those present in the swimming spore,
      or the secretion of an additional component required for adhesive curing. The
      novel use of atomic force microscopy in force modulation mode demonstrated that
      the adhesive secreted by most spores in the presence of BFA did not undergo the
      rapid curing process typical of control spores. However, some variation between
      zoospores was observed, with some cells showing no ultrastructural changes and
      normal adhesive curing. These results are discussed in relation to variations
      observed in the propensity and competence of spores to settle, which may be
      reflected in differential requirements for de novo synthesis and secretion of
      materials needed for full adhesion.

PMID- 11457901
TI  - Arabidopsis thaliana ecotype Cvi shows an increased tolerance to photo-oxidative
      stress and contains a new chloroplastic copper/zinc superoxide dismutase
      isoenzyme.
AB  - A new chloroplastic Cu/Zn-superoxide dismutase (SOD) isoenzyme was identified in
      Arabidopsis thaliana ecotype Cvi. Genetic analyses indicated that the new
      isoenzyme was encoded by a Cvi-specific allele of Csd2 that was named Csd2-2.
      Paraquat treatments of A. thaliana ecotypes Ler and Cvi resulted in higher levels
      of chloroplastic Cu/Zn-SOD activity in Cvi, suggesting that the Cvi isoenzyme has
      a higher stability and/or turnover rate than the Ler variant under photo
      oxidative conditions. In addition, Cvi showed a higher tolerance to paraquat
      treatments. Hybrid plant populations expressing Csd2-2 also exhibited an
      increased tolerance, suggesting that the Cvi isoenzyme is one of the factors that
      contribute to a better fitness in photo-oxidative stress conditions.

PMID- 11457902
TI  - The expression of tgas118, encoding a defensin in Lycopersicon esculentum, is
      regulated by gibberellin.
AB  - A flower specific cDNA, tgas118, has been isolated after differential screening
      of a gib-1 anther cDNA library of Lycopersicon esculentum. The corresponding mRNA
      was present in all tissues analysed. Northern blot analysis revealed that in wild
      type tomato the gene was predominantly expressed throughout flower development,
      while in the gibberellin (GA)-deficient mutant of tomato (gib-1) the abundance
      declined. Treatment of the mutant with GA resulted in an accumulation of the
      tgas118 mRNA within hours in leaf and bud tissues. In the leaf, GA1, GA3 and GA9
      were effective in enhancing the expression while GA4 was not. In addition to GA,
      wounding and dehydration also increased the accumulation of tgas118 mRNA in leaf
      tissue. In situ hybridization showed that application of 50 ng GA3 bud(-1)
      induced a similar spatial expression of the tgas118 mRNA in gib-1 buds 24 h post
      treatment to that found in wild-type flower buds. The deduced TGAS118 protein
      displays up to 77% similarity with defensins and as its expression is up
      regulated by stimuli such as wounding it is proposed that it may play a role in
      protection against pathogens.

PMID- 11457903
TI  - Expression of six expansin genes in relation to extension activity in developing
      strawberry fruit.
AB  - Expansins are proteins which have been demonstrated to induce cell wall extension
      in vitro. The identification and characterization of six expansin cDNAs from
      strawberry fruit, termed FaExp3 to FaExp7, as well as the previously identified
      FaExp2 is reported here. Analysis of expansin mRNAs during fruit development and
      in leaves, roots and stolons revealed a unique pattern of expression for each
      cDNA. FaExp3 mRNA was present at much lower levels than the other expansin mRNAs
      and was expressed in small green fruit and in ripe fruit. FaExp4 mRNA was present
      throughout fruit development, but was more strongly expressed during ripening.
      FaExp5 was the only clone to show fruit specific expression which was up
      regulated at the onset of ripening. FaExp6 and FaExp7 mRNAs were present at low
      levels in the fruit with highest expression in stolon tissue. During fruit
      development FaExp6 had the highest expression at the white, turning and orange
      stages whereas expression of FaExp7 was highest in white fruit. The expression
      profiles of FaExp2 and FaExp5 in developing fruit were similar except that FaExp2
      was induced at an earlier stage. Analysis of expansin protein by Western blotting
      using an antibody raised against CsExp1 from cucumber hypocotyls identified two
      bands of 29 and 31 kDa from developing fruit. Protein extracts from developing
      fruit were assayed for extension activity. Considerable rates of extension were
      observed with extracts from ripening fruit, but no extension was observed with
      protein from unripe green fruit. These results demonstrate the presence of at
      least six expansin genes in strawberry fruit and that during ripening the fruit
      acquires the ability to cause extension in vitro, characteristic of expansin
      action.

PMID- 11457904
TI  - Both light-dependent protochlorophyllide oxidoreductase A and protochlorophyllide
      oxidoreductase B are down-regulated in the slender mutant of barley.
AB  - The gibberellin-insensitive overgrowth mutant of barley, slender, exhibits
      altered expression of a number of nuclear genes in comparison with the wild type.
      There is a particularly marked reduction in slender seedlings of transcript
      encoding protochlorophyllide oxidoreductase (POR), the enzyme which catalyses the
      penultimate and only light-requiring step in chlorophyll biosynthesis. The
      expression of the two barley genes encoding light-dependent POR, PORA and PORB
      was investigated. Expression of both genes was found to be reduced in slender
      seedlings relative to the wild type, in both etiolated and light-grown leaf
      tissue; this was most marked in the zone of rapid cell extension. Western blot
      analysis showed that POR protein was also less abundant in etiolated and in light
      grown slender than in the equivalent wild-type leaf tissue, although the effect
      was less pronounced than at the transcript level. Protochlorophyllide content in
      etiolated slender seedlings was reduced in comparison with wild-type seedlings,
      though chlorophyll content in light-grown leaf blades was unaffected. The
      reduction in POR expression in slender barley may reflect a novel response to the
      constitutive activation of gibberellin signalling in this mutant. Despite the
      consequences of the mutation for POR gene expression, slender seedlings develop
      apparently normal chloroplasts in the light, and etioplasts with well-defined
      prolamellar bodies when grown in continuous darkness. This suggests that the POR
      content of wild-type barley seedlings is well in excess of the minimum required
      for normal plastid development.

PMID- 11457905
TI  - Genotype-dependent proteolytic response of spring wheat to water deficiency.
AB  - Changes in proteolytic activities in response to water deficiency have been
      investigated in ten genotypes of spring wheat (Triticum aestivum L.) differing in
      response to water deficit stress and ability to acclimate. To determine
      subcellular localization and the type of proteases, mesophyll protoplasts
      isolated from wheat leaves were purified. Proteolytic activities were assayed
      using azocasein in the case of vacuolar proteinases at pH 5.0 and 125I-lysozyme
      in the case of extravacuolar ATP-dependent proteinases at pH 8.2. ATP-dependent
      proteolytic activity was found to be confined to the extravacuolar fraction while
      the azocaseinolytic activity to vacuoles. Dehydration increased vacuolar
      azocaseinolytic activity at both stages of plant development (shooting and
      heading), but the increase was significantly lower in more tolerant genotypes.
      The extravacuolar energy-dependent 125I-lysozyme degradation was low at the
      shooting stage but it was higher in the genotypes with a greater critical water
      saturation deficit. At the heading phase in the non-acclimated flag leaves ATP
      dependent 125I-lysozyme degradation decreased in a genotype-dependent manner, but
      was enhanced upon acclimation to the same extent irrespective to the genotype
      ability to acquire dehydration tolerance during acclimation. The results
      presented indicate that both pathways of protein degradation are interlinked upon
      dehydration and are genotype dependent.

PMID- 11457906
TI  - Diffusion pathway for oxygen into highly thermogenic florets of the arum lily
      Philodendron selloum.
AB  - Thermogenic inflorescences of some arum lilies have the highest rates of
      respiration known among plants. Peak rates of oxygen consumption in the sterile
      male florets of Philodendron selloum Koch exceed 0.3 micromol x s(-1) x g(-1)
      when the inflorescence warms to 38 degrees C. This study describes the morphology
      of the oxygen diffusion pathway between the atmosphere and the parenchymal cells
      of the florets. Dimensions of the florets, stomata, interstitial gas network, and
      cells provide data for diffusion models of the PO2 profiles at each level of the
      'oxygen cascade'. The lowest calculated PO2 of 4.7 kPa (35 mmHg) at the axis of
      the thickest part of the floret indicates that maximum respiration does not reach
      the point of diffusion-limitation, confirming earlier physiological measurements
      of the dependence of oxygen consumption rate on environmental PO2. Adequate
      aeration of all cells is achieved by appropriate floret size, despite a stomatal
      density less than 5%, and interstitial gas fraction less than 2%, of values
      commonly found in leaves.

PMID- 11457907
TI  - Remobilization of cadmium in maturing shoots of near isogenic lines of durum
      wheat that differ in grain cadmium accumulation.
AB  - Cadmium accumulation in grain of durum wheat (Triticum turgidum L. var. durum)
      represents a concern to consumers. In an effort to understand the regulation of
      Cd accumulation in maturing grain, the remobilization of 109Cd applied to stem
      and flag leaves was examined in two near-isogenic lines that differ in grain Cd
      accumulation. Absorbed 109Cd was primarily retained in the labelling flap (50-54%
      and 65-80% for stem and flag leaves, respectively). Cadmium exported from the
      stem flap initially (3 d) accumulated in the stem in a declining gradient towards
      the head. Subsequent remobilization of Cd deposited in the stem was associated
      with Cd accumulation in the grain. Cadmium exported from the flag leaf flap was
      primarily directed to the grain. Little (<1%) Cd accumulated in the glumes or
      rachis, and transport of Cd to shoot tissues below the flag leaf node was low
      (<1%). On average, 9% and 17% of absorbed 109Cd accumulated in the grain 14 d
      after labelling the stem and flag leaf, respectively. Irrespective of labelling
      position, the low Cd-accumulating isoline averaged 1.5-2-fold lower Cd
      accumulation per grain and Cd concentration in the grain than the high Cd
      accumulating isoline. Cadmium accumulation in the grain was inversely correlated
      with Cd retention in the stem (stem labelled) and labelling flap (flag leaf
      labelled) for both isolines. Cadmium translocation to the grain was not inhibited
      by Zn when both were applied simultaneously (50 pM 109Cd; 0.5 microM 65Zn) to the
      flag leaf. These results show that elevated remobilization of Cd from the leaves
      and stem to the maturing grain may be partially responsible for the high
      accumulation of Cd in durum wheat grain.

PMID- 11457908
TI  - Growth-induced water potentials originate from wall yielding during growth.
AB  - Multicellular plants display growth-induced water potentials that generate
      tensions on water in the apoplast and move water into the growing cells. The
      potentials are sometimes assumed to arise from wall yielding, keeping the turgor
      pressure below what otherwise would occur. There has been no direct test of this
      theory, and therefore whole plants or growing regions of stems (hypocotyls) of
      dark-grown soybean (Glycine max L. Merr.) seedlings were sealed in a pressure
      chamber, and wall yielding was decreased by applying external pressure. In whole
      plants, external pressure had little effect because the plants and water supply
      were uniformly exposed to the pressure. If pressure was applied to the stem while
      the roots were outside in water, stem elongation was markedly inhibited because
      the pressure raised the water potential of the growing region and decreased water
      entry, reducing wall yielding. Further increasing the pressure prevented water
      entry completely and measured the tensions in the apoplast in the same growing
      regions. Tensions were about 0.19 MPa at low external pressure, but diminished as
      wall yielding was inhibited. At external pressures of about 0.63 MPa, wall
      yielding was abolished and tensions approached zero. There was a linear relation
      between wall yielding and tension, supporting the theory that wall yielding
      lowers the turgor thus causing most of the growth-induced water potential.

PMID- 11457909
TI  - Iron deficiency-associated changes in the composition of the leaf apoplastic
      fluid from field-grown pear (Pyrus communis L.) trees.
AB  - Experiments have been carried out with field-grown pear trees to investigate the
      effect of iron chlorosis on the composition of the leaf apoplast. Iron deficiency
      was associated with an increase in the leaf apoplastic pH from the control values
      of 5.5-5.9 to 6.5-6.6, as judged from direct pH measurements in apoplastic fluid
      obtained by centrifugation and fluorescence of leaves incubated with 5-CF. The
      major organic acids found in leaf apoplastic fluid of iron-deficient and iron
      sufficient pear leaves were malate, citrate and ascorbate. The total
      concentration of organic acids was 2.9 mM in the controls and increased to 5.5 mM
      in Fe-deficient leaves. The total apoplastic concentration of inorganic cations
      (Ca, K and Mg) increased with Fe deficiency from 15 to 20 mM. The total
      apoplastic concentration of inorganic anions (Cl-, NO3-, SO4(2-) and HPO4(2-))
      did not change with Fe deficiency. Iron concentrations decreased from 4 to 1.6
      microM with Fe deficiency. The major Fe species predicted to exist in the
      apoplast was [FeCitOH](-1) in both Fe-sufficient and deficient leaves. Organic
      acids in whole leaf homogenates increased from 20 to 40 nmol x m(-2) with Fe
      deficiency. The accumulation of organic anions in the Fe-deficient leaves does
      not appear to be associated to an increased C fixation in leaves, but rather it
      seems to be a consequence of C transport via xylem.

PMID- 11457910
TI  - Dormancy, ABA content and sensitivity of a barley mutant to ABA application
      during seed development and after ripening.
AB  - Assessment of dormancy inception, maintenance and release was studied for
      artificially dried immature seeds harvested throughout seed development in the
      barley cv. Triumph and its mutant line TL43. Each was grown in Spain and Scotland
      under low and high dormancy inducing conditions, respectively. Both TL43 and
      Triumph followed a similar pattern of release from dormancy across the seasons,
      although seeds of TL43 were able to germinate at an earlier seed development
      stage. Abscisic acid (ABA) content was also studied in immature grains throughout
      the seed development period. Total amount of ABA in seeds of Triumph and TL43 was
      higher in plants grown in Scotland than in Spain. However, no clear genotypic
      differences in ABA pattern in the course of grain development could be detected
      whilst significant genotypic differences were observed for germination percentage
      (GP). Endogenous ABA content alone throughout grain development did not explain
      genetic differences in GP within environments. Environmental and genetic
      differences in dormancy were also observed on mature seeds throughout the after
      ripening period. The initial germination (GP(0)) played a key role in the
      sensitivity to ABA of post-harvest mature seeds. For the same after-ripening
      stage, TL43 was more insensitive to exogenous ABA than Triumph. However, ABA
      responses in seeds of the two genotypes with similar GP(0) at different after
      ripening stages were comparable. Therefore, differences in exogenous ABA
      sensitivity of post-harvest mature grain of these two genotypes seemed to be
      determined by, or coincident with, the initial germination percentage.

PMID- 11457911
TI  - Evidence for down-regulation of ethanolic fermentation and K+ effluxes in the
      coleoptile of rice seedlings during prolonged anoxia.
AB  - Ethanolic fermentation, the predominant catabolic pathway in anoxia-tolerant rice
      coleoptiles, was manipulated in excised and 'aged' tissues via glucose feeding.
      Coleoptiles with exogenous glucose survived 60 h of anoxia, as evidenced by
      vigorous rates of K+ and phosphate net uptake and growth of roots and shoots when
      re-aerated. In contrast, coleoptiles without exogenous glucose showed net losses
      of K+ and phosphates starting 12 h after anoxia was imposed and these did not
      recover fully when re-aerated after 60 h of anoxia. Ethanol production (micromol
      x g(-1) FW x h(-1)) declined from about 7.5 during the first 12 h of anoxia to 5
      or 2.2 after 48-60 h, in coleoptiles with or without exogenous glucose,
      respectively. Carbohydrate concentrations changed only slightly in anoxic
      coleoptiles with exogenous glucose due to net glucose uptake at 2.6 micromol x g(
      1) FW x h(-1). Ethanolic fermentation, and therefore ATP production, may have
      been down-regulated after an initial period of acclimation to anoxia in
      coleoptiles with exogenous glucose. Maintenance requirements for energy were
      assessed to be 3.4-7.6-fold lower in these anoxic coleoptiles than published
      estimates for non-growing aerated leaf tissues. A modest part of the required
      economy in energy consumption would have been derived from diminished ion
      transport; anoxia reduced K+ and phosphate net uptake by 70-90% in these
      coleoptiles. K+ efflux was 10-fold lower in anoxic than in aerated coleoptiles
      with exogenous glucose. Using the unidirectional efflux equation, the membrane
      permeability to K+ was estimated to be 17-fold lower in anoxic than in aerated
      coleoptiles, presumably due to predominantly closed K+ channels.

PMID- 11457912
TI  - Sulphur nutrition affects delivery and metabolism of S in developing endosperms
      of wheat.
AB  - Experiments were conducted to investigate the effect of S nutrition and
      availability on the forms of S and N in the endosperm cavity and endosperm of
      wheat, and on the capacity of the endosperm to utilize those compounds for the
      synthesis of proteins. Plants were grown in solution culture with 2 mM N and
      either 200 microM S (high-S) or 50 microM S (low-S) and all nutrients were
      withdrawn at various times from booting until 8 d post-anthesis. Sulphate was the
      major form of soluble S in the endosperm cavity and endosperm of high-S plants
      during the time of rapid grain development. By contrast, glutathione (GSH) was
      the major form of soluble S in the endosperm cavity and in the endosperm in low-S
      plants. Crude extracts of endosperm tissue from both high-S and low-S plants
      supported (i) the hydrolysis of GSH to gamma-glutamyl cysteine and glycine, and
      of gamma-glutamyl cysteine to glutamate and cysteine, and (ii) sulphate-dependent
      PPi-ATP exchange and the sulphydration of O-acetylserine catalysed by ATP
      sulphurylase and cysteine synthase, respectively. High-S nutrition enhanced the
      in vitro rates of ATP sulphurylase and cysteine synthase.

PMID- 11457913
TI  - Hydraulic vulnerability, vessel refilling, and seasonal courses of stem water
      potential of Sorbus aucuparia L. and Sambucus nigra L.
AB  - Differences in the seasonal variation in stem water potential between the two
      shrub species Sorbus aucuparia and Sambucus nigra were related with their
      vulnerability to xylem cavitation. It was also demonstrated indirectly that the
      two species differ in the extent to which they reverse cavitation. Seasonal
      variation in stem water potential was investigated during three growing seasons
      with in situ stem psychrometers. Sorbus experienced wide water potential
      variations and reached a minimum of -4.2 MPa during drought. Under the same
      microclimatic conditions, Sambucus experienced consistent stem water potentials
      with a minimum of -1.7 MPa. The relationship between percentage loss in hydraulic
      conductivity (PLC) and water potential (hydraulic vulnerability curve) of the two
      species differed in shape: a flat curve with nearly total loss of conductivity at
      -6 MPa was found for SORBUS: Sambucus showed a steep vulnerability curve with 90%
      loss conductivity at -2.2 MPa. Thus, Sambucus is extremely vulnerable to
      cavitation, but Sorbus is an almost invulnerable species. This different
      cavitation resistance adjusted the ranges of field stem water potential that the
      species experienced. Finally, seasonal courses of naturally occurring (native)
      embolism were compared with calculated PLC courses. This comparison indicates
      that Sorbus did not refill embolized xylem vessels whereas Sambucus reversed
      embolism. It was concluded that species which are highly vulnerable to cavitation
      and drought-induced embolism need refilling of embolized vessels as well as
      isohydric water potential patterns as two strategies of survival.

PMID- 11457914
TI  - Specific flavonoids induced nod gene expression and pre-activated nod genes of
      Rhizobium leguminosarum increased pea (Pisum sativum L.) and lentil (Lens
      culinaris L.) nodulation in controlled growth chamber environments.
AB  - The gram-negative soil bacteria Rhizobium spp. infect and establish a nitrogen
      fixing symbiosis with legume crops which involves the mutual exchange of
      diffusable signal molecules. In this study, Rhizobium leguminosarum containing a
      nod-lacZ gene fusion was used to screen the most effective plant-to-bacteria
      signal molecules for pea and lentil and the induction conditions. Out of a number
      of signal compounds including apigenin, daidzein, genistein, hesperetin,
      kaempferol, luteolin, naringenin, and rutin, hesperetin and naringenin were found
      to be the most effective plant-to-bacteria signal molecules. The induction of nod
      genes was temperature-dependent, where nod gene induction was decreased with
      dropping incubation temperature. The combination of hesperetin at 7 microM and
      naringenin at 3 microM resulted in better induction of nod gene activities
      compared to either hesperetin or naringenin alone. Nodulation and plant dry
      matter accumulation of pea and lentil plants receiving preinduced R.
      leguminosarum were higher than those of plants receiving uninduced R.
      leguminosarum cells in controlled environment growth chamber conditions.
      Preinduced Rhizobium with hesperetin at a concentration of 10 microM increased
      nodule number on average by 60.5% and dry matter accumulation by 14% in field pea
      at 17 degrees C, while it was 32% and 9% at 24 degrees C, respectively.
      Similarly, averaged over two rhizobial strains, a 59% and 6% increase in nodule
      number and biomass production at 17 degrees C, and a 39% and 27% at 24 degrees C,
      were obtained from lentil inoculated with hesperetin-induced R. leguminosarum,
      respectively.

PMID- 11457915
TI  - Accumulation of plastid lipid-associated proteins (fibrillin/CDSP34) upon
      oxidative stress, ageing and biotic stress in Solanaceae and in response to
      drought in other species.
AB  - Plastid lipid-associated proteins, also termed fibrillin/CDSP34 proteins, are
      known to accumulate in fibrillar-type chromoplasts such as those of ripening
      pepper fruit, and in leaf chloroplasts from Solanaceae plants under abiotic
      stress conditions. It is shown here that treatments generating active oxygen
      species (high light combined with low temperature, gamma irradiation or methyl
      viologen treatment) result in potato CDSP34 gene induction and protein
      accumulation in leaves. Using transgenic tomato plants containing the pepper
      fibrillin promoter, a significant increase in promoter activity in leaves
      subjected to biotic stress, namely bacterial infections, was observed. In WT, a
      higher level of the endogenous fibrillin/CDSP34 protein is also observed after
      infection by E. chrysanthemi strain 3739. In addition to stress-related
      induction, a progressive increase in the fibrillin promoter activity is noticed
      during ageing in various tomato photosynthetic tissues and this increase
      correlates with a higher abundance of the endogenous protein in WT leaves. It is
      proposed that a mechanism related to oxidative events plays an essential role in
      the regulation of fibrillin/CDSP34 genes during stress and also during
      development. Using a biolistic transient expression assay, the pepper fibrillin
      promoter is found to be active in various dicot species, but not in monocots.
      Further, substantially increased levels of fibrillin/ CDSP34 proteins are shown
      in various dicotyledonous and monocotyledonous plants in response to water
      deficit.

PMID- 11457916
TI  - Possible explanation of the disparity between the in vitro and in vivo
      measurements of Rubisco activity: a study in loblolly pine grown in elevated
      pCO2.
AB  - Rubisco activity can be measured using gas exchange (in vivo) or using in vitro
      methods. Commonly in vitro methods yield activities that are less than those
      obtained in vivo. Rubisco activity was measured both in vivo and in vitro using a
      spectrophotometric technique in mature Pinus taeda L. (loblolly pine) trees grown
      using free-air CO2 enrichment in elevated (56 Pa) and current (36 Pa) pCO2. In
      addition, for studies where both in vivo and in vitro values of Rubisco activity
      were reported net CO2 uptake rate (A) was modelled based on the in vivo and in
      vitro values of Rubisco activity reported in the literature. Both the modelling
      exercise and the experimental data showed that the in vitro values of Rubisco
      activity were insufficient to account for the observed values of A. A
      trichloroacetic acid (TCA) precipitation of the protein from samples taken in
      parallel with those used for activity analysis was co-electrophoresed with the
      extract used for determining in vitro Rubisco activity. There was significantly
      more Rubisco present in the TCA precipitated samples, suggesting that the
      underestimation of Rubisco activity in vitro was attributable to an insufficient
      extraction of Rubisco protein prior to activity analysis. Correction of in vitro
      values to account for the under-represented Rubisco yielded mechanistically valid
      values for Rubisco activity. However, despite the low absolute values for Rubisco
      activity determined in vitro, the trends reported with CO2 treatment concurred
      with, and were of equal magnitude to, those observed in Rubisco activity measured
      in vivo.

PMID- 11457917
TI  - Acclimation of plants to light gradients in leaf canopies: evidence for a
      possible role for cytokinins transported in the transpiration stream.
AB  - The mechanism of response of plants to vertical light intensity gradients in leaf
      canopies was investigated. Since shaded leaves transpire less than leaves in high
      light, it was hypothesized that cytokinins (CKs) carried by mass transport in the
      transpiration stream would be distributed over the leaf area of partially shaded
      plants parallel to the gradient in light intensity. It was also hypothesized that
      this causes the distribution of leaf growth, leaf N and photosynthetic capacity,
      and possibly chloroplast acclimation as observed in plants growing in leaf
      canopies. In a field experiment, the distribution of Ca, N and CKs in a bean leaf
      canopy of a dense and an open stand supported the concept of a role for CKs in
      the response of N allocation to the light gradient when a decreasing sensitivity
      for CKs with increasing leaf age is assumed. Both shading of one leaf of the pair
      of primary bean leaves and independent reduction of its transpiration rate in a
      growth cabinet experiment caused lower dry mass, N and Ca per unit leaf area in
      comparison to the opposite not treated leaf. Shading caused a parallel reduction
      in CK concentration, which supports the hypothesis, but independent reduction of
      transpiration rate failed to do the same. Application of benzylaminopurine (BA)
      counteracted the reduction caused by shade of leaf N, photosynthetic capacity and
      leaf area growth. The experiments show an important role for the transpiration
      stream in the response of plants to light gradients. Evidence is presented here
      that CKs carried in the transpiration stream may be important mediators for the
      acclimation of plants to leaf canopy density.

PMID- 11457918
TI  - An efficient method for extraction of RNA from rice leaves at different ages
      using benzyl chloride.
AB  - With a conventional method of RNA extraction using an acid guanidinium
      thiocyanate-water-saturated phenol-chloroform mixture, extraction efficiency of
      extractable RNA to total RNA (extractable RNA+ residual RNA) in rice leaves at
      various ages was 54-69%. With a new method, an improvement of the above, using
      benzyl chloride instead of water-saturated phenol together with further
      maceration with a small amount of quartz sand, the efficiency was increased to 81
      95%. When RNA fractions obtained with the improved method were subjected to
      agarose gel electrophoresis, intact bands of 25 S and 17 S rRNAs were detected.
      With a DNA probe for rice rbcS, only a single band was observed on the blotted
      membrane. These results indicate that the improved extraction method of RNA with
      benzyl chloride is useful for quantitative and qualitative analysis of RNA in
      plant tissues such as stiff leaves of rice.

PMID- 11457919
TI  - Mutagenesis and heterologous expression in yeast of a plant Delta6-fatty acid
      desaturase.
AB  - Membrane-bound microsomal fatty acid desaturases are known to have three
      conserved histidine boxes, comprising a total of up to eight histidine residues.
      Recently, a number of deviations from this consensus have been reported, with the
      substitution of a glutamine for the first histidine residue of the third
      histidine box being present in the so called 'front end' desaturases. These
      enzymes are also characterized by the presence of a cytochrome b5 domain at the
      protein N-terminus. Site-directed mutagenesis has been used to probe the
      functional importance of a number of amino acid residues which comprise the third
      histidine box of a 'front end' desaturase, the borage Delta6-fatty acid
      desaturase. This showed that the variant glutamine in the third histidine box is
      essential for enzyme activity and that histidine is not able to substitute for
      this residue.

PMID- 11457920
TI  - The Arabidopsis AtEm1 promoter is active in Brassica napus L. and is temporally
      and spatially regulated.
AB  - The promoter of the Arabidopsis thaliana L. AtEm1 gene encoding a late
      embryogenesis abundant protein was fused to the beta-glucuronidase reporter gene
      and introduced into Brassica napus. The promoter is highly active in the vascular
      tissues of embryo and pollen grains and also active in petals, sepals, caulinar
      leaves, and carpels.

PMID- 11457921
TI  - Antigen retrieval techniques: current perspectives.
AB  - Development of the antigen retrieval (AR) technique, a simple method of boiling
      archival paraffin-embedded tissue sections in water to enhance the signal of
      immunohistochemistry (IHC), was the fruit of pioneering efforts guided by the
      philosophy of rendering IHC applicable to routine formalin-fixed, paraffin
      embedded tissues for wide application of IHC in research and clinical pathology.
      On the basis of thousands of articles and many reviews, a book has recently been
      published that summarizes basic principles for practice and further development
      of the AR technique. Major topics with respect to several critical issues, such
      as the definition, application, technical principles, and further studies of the
      AR technique, are highlighted in this article. In particular, a further
      application of the heat-induced retrieval approach for sufficient extraction of
      nucleic acids in addition to proteins, and standardization of routine IHC based
      on the AR technique in terms of a test battery approach, are also addressed.
      Furthermore, understanding the mechanism of the AR technique may shed light on
      facilitating the development of molecular morphology.

PMID- 11457922
TI  - DNA fiber mapping techniques for the assembly of high-resolution physical maps.
AB  - High-resolution physical maps are indispensable for directed sequencing projects
      or the finishing stages of shotgun sequencing projects. These maps are also
      critical for the positional cloning of disease genes and genetic elements that
      regulate gene expression. Typically, physical maps are based on ordered sets of
      large insert DNA clones from cosmid, P1/PAC/BAC, or yeast artificial chromosome
      (YAC) libraries. Recent technical developments provide detailed information about
      overlaps or gaps between clones and precisely locate the position of sequence
      tagged sites or expressed sequences, and thus support efforts to determine the
      complete sequence of the human genome and model organisms. Assembly of physical
      maps is greatly facilitated by hybridization of non-isotopically labeled DNA
      probes onto DNA molecules that were released from interphase cell nuclei or
      recombinant DNA clones, stretched to some extent and then immobilized on a solid
      support. The bound DNA, collectively called "DNA fibers," may consist of single
      DNA molecules in some experiments or bundles of chromatin fibers in others. Once
      released from the interphase nuclei, the DNA fibers become more accessible to
      probes and detection reagents. Hybridization efficiency is therefore increased,
      allowing the detection of DNA targets as small as a few hundred base pairs. This
      review summarizes different approaches to DNA fiber mapping and discusses the
      detection sensitivity and mapping accuracy as well as recent achievements in
      mapping expressed sequence tags and DNA replication sites.

PMID- 11457923
TI  - Immuno-EM localization of GFP-tagged yolk proteins in C. elegans using microwave
      fixation.
AB  - Because of the presence of a low-permeability cuticle covering the animal,
      fixation of C. elegans tissue for immunoelectron microscopy has proved very
      difficult. Here we applied a microwave fixation protocol to improve penetration
      of fixatives before postembedding immunogold labeling. Using this technique, we
      were able to successfully localize several components of yolk (YP170) trafficking
      in both wild-type and transgenic strains expressing a vitellogenin::green
      fluorescent protein fusion (YP170::GFP). Green fluorescent protein (GFP) and its
      variants are commonly used as markers to localize proteins in transgenic C.
      elegans using fluorescence microscopy. We have developed a robust method to
      localize GFP at the EM level. This procedure is applicable to the
      characterization of transgenic strains in which GFP is used to mark particular
      proteins or cell types and will undoubtedly be very useful for high-resolution
      analysis of marked structures.

PMID- 11457924
TI  - Isolation of mature spinal motor neurons and single-cell analysis using the comet
      assay of early low-level DNA damage induced in vitro and in vivo.
AB  - We developed an isolation technique for motor neurons from adult rat spinal cord.
      Spinal cord enlargements were discretely microdissected into ventral horn tissue
      columns that were trypsin-digested and subjected to differential low-speed
      centrifugation to fractionate ventral horn cell types. A fraction enriched in
      alpha-motor neurons was isolated. Motor neuron enrichment was verified by
      immunofluorescence for choline acetyltransferase and prelabeling axon projections
      to skeletal muscle. Adult motor neurons were isolated from naive rats and were
      exposed to oxidative agents or were isolated from rats with sciatic nerve lesions
      (avulsions). We tested the hypothesis, using single-cell gel electrophoresis
      (comet assay), that hydrogen peroxide, nitric oxide, and peroxynitrite exposure
      in vitro and axotomy in vivo induce DNA damage in adult motor neurons early
      during their degeneration. This study contributes three important developments in
      the study of motor neurons. It demonstrates that mature spinal motor neurons can
      be isolated and used for in vitro models of motor neuron degeneration. It shows
      that adult motor neurons can be isolated from in vivo models of motor neuron
      degeneration and evaluated on a single-cell basis. This study also demonstrates
      that the comet assay is a feasible method for measuring DNA damage in individual
      motor neurons. Using these methods, we conclude that motor neurons undergoing
      oxidative stress from reactive oxygen species and axotomy accumulate DNA damage
      early in their degeneration.

PMID- 11457925
TI  - SLC26A2 (diastrophic dysplasia sulfate transporter) is expressed in developing
      and mature cartilage but also in other tissues and cell types.
AB  - Mutated alleles of the SLC26A2 (diastrophic dysplasia sulfate transporter or
      DTDST) gene cause each of the four recessive chondrodysplasias, i.e., diastrophic
      dysplasia (DTD), multiple epiphyseal dysplasia (MED), atelosteogenesis Type II
      (AO2), and achondrogenesis Type IB (ACG1B). SLC26A2 acts as an Na(+)-independent
      sulfate/chloride antiporter and belongs to the SLC26 anion transporter gene
      family, currently consisting of six homologous human members. Although Northern
      analysis has indicated some expression in all tissues studied, the only tissue
      known to be affected by SLC26A2 mutations is cartilage. Abundant SLC26A2
      expression has previously been detected in normal human colon by in situ
      hybridization. We have used in situ hybridization and immunohistochemistry to
      examine multiple normal tissues for the expression of human SLC26A2. As expected,
      a strong signal for SLC26A2 mRNA and protein immunostaining were detected in
      developing fetal hyaline cartilage, while bronchial cartilage showed mRNA
      expression in adult tissues. SLC26A2 expression could also be detected in eccrine
      sweat glands, in bronchial glands, and in placental villi. In addition,
      immunoreactivity for the SLC26A2 protein was observed in exocrine pancreas. Our
      results suggest a more limited expression pattern for SLC26A2 than that found by
      Northern analysis. However, SLC26A2 expression is also detected in tissues not
      affected in chondrodysplasias caused by SLC26A2 mutations.

PMID- 11457926
TI  - Immunohistochemistry of omega class glutathione S-transferase in human tissues.
AB  - Omega class glutathione transferase (GSTO) has been recently described in a
      number of mammalian species. We used immunohistochemistry to determine the
      cellular and tissue distribution of GSTO1-1 in humans. Expression of GSTO1-1 was
      abundant in a wide range of normal tissues, particularly liver, macrophages,
      glial cells, and endocrine cells. We also found nuclear staining in several types
      of cells, including glial cells, myoepithelial cells of the breast,
      neuroendocrine cells of colon, fetal myocytes, hepatocytes, biliary epithelium,
      ductal epithelium of the pancreas, Hoffbauer cells of the placenta, and
      follicular and C-cells of the thyroid. These observations and the known activity
      of GSTO1-1 suggest biological functions that are not shared with other GSTs.

PMID- 11457927
TI  - The role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle
      regeneration. Studies in TNF-alpha(-/-) and TNF-alpha(-/-)/LT-alpha(-/-) mice.
AB  - The role of tumor necrosis factor-alpha (TNF-alpha), an important mediator of the
      inflammatory response after injury, was investigated in regenerating skeletal
      muscle. The pattern of expression of TNF-alpha during muscle regeneration was
      examined by immunohistochemistry in tissue sections of crush-injured or
      transplanted muscle autografts and in primary cultures of adult skeletal muscle.
      TNF-alpha was highly expressed in injured myofibers, inflammatory cells,
      endothelial cells, fibroblasts, and mast cells. Myoblasts and myotubes also
      expressed TNF-alpha in primary muscle cultures and tissue sections. The essential
      role of TNF-alpha and its homologue lymphotoxin-alpha (LT-alpha) during muscle
      regeneration was assessed by basic histology in TNF-alpha(-/-) and TNF-alpha(-/
      )/LT-alpha(-/-) mice. No difference was apparent in the onset or pattern of
      muscle regeneration (i.e., inflammatory response, activation and fusion of
      myoblasts) between the two strains of null mice or between nulls and normal
      control mice. However, both strains of null mice appeared more prone to bystander
      damage of host muscle and regeneration distant from the site of
      injury/transplantation. Although expression of TNF-alpha may play an important
      role in muscle regeneration, the studies in the null mice show that redundancy
      within the cytokine system (or some other response) can effectively compensate
      for the absence of TNF-alpha in vivo.

PMID- 11457928
TI  - Extensive DNA fragmentation in oxyphilic cell lesions of the thyroid.
AB  - The in situ end-labeling (ISEL) method demonstrates DNA fragmentation, commonly
      regarded as a marker of apoptosis. We investigated by the ISEL procedure a series
      of 52 thyroid lesions, including 24 lesions of mitochondrion-rich oxyphilic
      cells, both benign and malignant, and 28 non-oxyphilic control tumors. A high
      percentage of nuclear ISEL staining (approximating to 100% in most cases) was
      observed in the vast majority of oxyphilic cells from both adenomas and
      carcinomas, in the absence of morphological apoptotic changes and with no
      immunocytochemical evidence of caspase activation. This pattern of DNA
      fragmentation was not observed in non-oxyphilic lesions and was confirmed in
      total extracted DNA. Moreover, a peculiar cytoplasmic staining was also observed
      in oxyphilic cells from both benign and malignant lesions, probably related to
      abnormal fragmentation of mitochondrial DNA. Similar staining patterns were
      detected in oxyphilic cell tumors of other organs (parathyroids, salivary glands,
      and kidneys). These findings are consistent with an extensive DNA fragmentation
      peculiar to oxyphilic cells, which is not directly related to apoptosis and whose
      origin and biological significance are presently unknown.

PMID- 11457929
TI  - Immunolocalization of NA(+),K(+)-ATPase in the branchial cavity during the early
      development of the European lobster Homarus gammarus (Crustacea, Decapoda).
AB  - We examined the ontogeny of the osmoregulatory sites of the branchial cavity in
      embryonic and early postembryonic stages of the European lobster Homarus gammarus
      through transmission electron microscopy, immunofluorescence microscopy, and
      immunogold electron microscopy using a monoclonal antibody IgGalpha(5) raised
      against the avian alpha-subunit of the Na(+),K(+)-ATPase. In mid-late embryos,
      Na(+),K(+)-ATPase was located along the pleurites and within the epipodite buds.
      In late embryos just before hatching, the enzyme was confined to the epipodite
      epithelia. After hatching, slight differentiations of ionocytes occured in the
      epipodites of larval stages. Na(+),K(+)-ATPase was also located in the ionocytes
      of the epipodites of larvae exposed to seawater (35.%o) and to dilute seawater
      (22.1 %o). After metamorphosis, the inner-side branchiostegite epithelium
      appeared as an additional site of enzyme location in postlarvae held in dilute
      seawater. Within the ionocytes, Na(+),K(+)-ATPase was mostly located along the
      basolateral infoldings. These observations are discussed in relation to the
      physiological shift from osmoconforming larvae to slightly hyper-regulating (in
      dilute seawater) postmetamorphic stages. The acquisition of the ability to hyper
      osmoregulate probably originates from the differentiation, on the epipodites and
      mainly along the branchiostegites, of ionocytes that are the site of ion pumping
      as evidenced by the location of Na(+),K(+)-ATPase.

PMID- 11457930
TI  - Quantitative cytochemical analysis of glucose-6-phosphate dehydrogenase activity
      in living isolated hepatocytes of European flounder for rapid analysis of
      xenobiotic effects.
AB  - There is a great need for rapid but reliable assays to determine quantitatively
      effects of xenobiotics on biological systems in environmental research.
      Hepatocytes of European flounder are sensitive to low-dose toxic stress. Glucose
      6-phosphate dehydrogenase (G6PDH) is the major source of NADPH in cells and is
      therefore of major importance for NADPH-dependent xenobiotic biotransformation
      and defense against toxic injury. These facts prompted us to develop a sensitive
      cytochemical method to detect G6PDH activity in living isolated flounder
      hepatocytes using the tetrazolium salt method. The intact plasma membrane did not
      appear to be a barrier for substrate, co-enzyme, and dye molecules because the
      intracellular enzyme reaction started immediately when incubation medium was
      added and could be monitored in real time per individual cell using image
      analysis. The reaction was effectively stopped for end point measurements by
      using 4% formaldehyde in 0.1 M phosphate buffer (pH 5.3). The final reaction
      product, formazan, was stable in hepatocytes for at least 12 days at 4C. This is
      the first time that a chromogenic histochemical assay is applied to living cells.
      This approach provides an easy tool for large-scale screening of xenobiotic
      metabolism and cellular stress defense.

PMID- 11457931
TI  - Evidence for three fast myosin heavy chain isoforms in type II skeletal muscle
      fibers in the adult llama (Lama glama).
AB  - Skeletal muscle fiber types classified on the basis of their content of different
      myosin heavy chain (MHC) isoforms were analyzed in samples from hindlimb muscles
      of adult sedentary llamas (Lama glama) by correlating immunohistochemistry with
      specific anti-MHC monoclonal antibodies, myofibrillar ATPase (mATPase)
      histochemistry, and quantitative histochemistry of fiber metabolic and size
      properties. The immunohistochemical technique allowed the separation of four pure
      (i.e., expressing a unique MHC isoform) muscle fiber types: one slow-twitch (Type
      I) and three fast-twitch (Type II) phenotypes. The same four major fiber types
      could be objectively discriminated with two serial sections stained for mATPase
      after acid (pH 4.5) and alkaline (pH 10.5) preincubations. The three fast-twitch
      fiber types were tentatively designated as IIA, IIX, and IIB on the basis of the
      homologies of their immunoreactivities, acid denaturation of their mATPase
      activity, size, and metabolic properties expressed at the cellular level with the
      corresponding isoforms of rat and horse muscles. Acid stability of their mATPase
      activity increased in the rank order IIA>IIX>IIB. The same was true for size and
      glycolytic capacity, whereas oxidative capacity decreased in the same rank order
      IIA>IIX>IIB. In addition to these four pure fibers (I, IIA, IIX, and IIB), four
      other fiber types with hybrid phenotypes containing two (I+IIA, IIAX, and IIXB)
      or three (IIAXB) MHCs were immunohistochemically delineated. These frequent
      phenotypes (40% of the semitendinosus muscle fiber composition) had overlapped
      mATPase staining intensities with their corresponding pure fiber types, so they
      could not be delineated by mATPase histochemistry. Expression of the three fast
      adult MHC isoforms was spatially regulated around islets of Type I fibers, with
      concentric circles of fibers expressing MHC-IIA, then MHC-IIX, and peripherally
      MHC-IIB. This study demonstrates that three adult fast Type II MHC isoproteins
      are expressed in skeletal muscle fibers of the llama. The general assumption that
      the very fast MHC-IIB isoform is expressed only in small mammals can be rejected.

PMID- 11457932
TI  - Carbonic anhydrase II associated with plasma membrane in a human pancreatic duct
      cell line (CAPAN-1).
AB  - The subcellular distribution of carbonic anhydrase II, either throughout the
      cytosol or in the cytoplasm close to the apical plasma membrane or vesicular
      compartments, suggests that this enzyme may have different roles in the
      regulation of pH in intra- or extracellular compartments. To throw more light on
      the role of pancreatic carbonic anhydrase II, we examined its expression and
      subcellular distribution in Capan-1 cells. Immunocytochemical analysis by light,
      confocal, and electron microscopy, as well as immunoblotting of cell homogenates
      or purified plasma membranes, was performed. A carbonic anhydrase II of 29 kD
      associated by weak bonds to the inner leaflet of apical plasma membranes of
      polarized cells was detected. This enzyme was co-localized with markers of Golgi
      compartments. Moreover, the defect of its targeting to apical plasma membranes in
      cells treated with brefeldin A was indicative of its transport by the Golgi
      apparatus. We show here that a carbonic anhydrase II is associated with the inner
      leaflet of apical plasma membranes and with the cytosolic side of the
      endomembranes of human cancerous pancreatic duct cells (Capan-1). These
      observations point to a role for this enzyme in the regulation of intra- and
      extracellular pH.

PMID- 11457933
TI  - Mast cell mediation of muscle and pulmonary injury following hindlimb ischemia
      reperfusion.
AB  - We have observed extensive mast cell degranulation in the reperfused hindlimb
      muscle of the mouse, accompanied by pathological changes within the muscle. As
      quantitated by the tissue:blood (125)I permeability ratio, both the hindlimbs and
      lungs exhibited a significant increment in permeability during hindlimb
      reperfusion. In lungs of the same mice, mast cell-derived chymase mMCP-1 coats
      alveolar macrophages, an event noted by us in acid-induced direct lung injury.
      Mast cells in the lung contain mMCP-1, whereas those in the muscle do not.
      Neither extensive muscle injury nor an increased pulmonary permeability index
      occurs in the mast cell-deficient W/W(v) mice. We conclude that the mast cell is
      a key mediator in both local ischemia-reperfusion injury (I-R) of muscle and
      consequent remote lung injury.

PMID- 11457934
TI  - Monitoring signal transduction in cancer: cDNA microarray for semiquantitative
      analysis.
AB  - This study targeted the development of a novel microarray tool to allow rapid
      determination of the expression levels of 58 different tyrosine kinase (tk) genes
      in small tumor samples. The goals were to define a reference probe for multi
      sample comparison and to investigate the variability and reproducibility of the
      image acquisition and RT-PCR procedures. The small number of tk genes on our
      arrays enabled us to define a reference probe by artificially mixing all genes on
      the arrays. Such a probe provided contrast reference for comparative
      hybridization of control and sample DNA and enabled cross-comparison of more than
      two samples against one another. Comparison of signals generated from multiple
      scanning eliminated the concern of photo bleaching and scanner intrinsic noise.
      Tests performed with breast, thyroid, and prostate cancer samples yielded
      distinctive patterns and suggest the feasibility of our approach. Repeated
      experiments indicated reproducibility of such arrays. Up- or downregulated genes
      identified by this rapid screening are now being investigated with techniques
      such as in situ hybridization.

PMID- 11457935
TI  - Proliferation and apoptosis measurements by color image analysis based on
      differential absorption.
AB  - Cell proliferation and apoptosis indices are important indicators for the
      prognosis and treatment of a variety of cancers. A method is described using
      differential absorption color image analysis to measure proliferation and
      apoptosis in tumor sections using BrdU (5' bromodeoxyuridine) incorporation and
      immunohistochemistry and terminal deoxytransferase nick end-labeling (TUNEL).
      Nuclei were labeled with streptavidin-peroxidase-diaminobenzidine (DAB) secondary
      detection. The differential absorption method uses a computer-controlled
      microscope equipped with a tunable filter and digital camera to take advantage of
      the spectral differences of stained objects of interest. Images collected at
      defined wavelengths are divided and scaled to form ratio images in which the
      hematoxylin- or DAB-stained nuclei have intensity ranges far above those of
      surrounding structures. Using brightness thresholding followed by selection based
      on nuclear size and shape parameters, binary images were formed of the
      BrdU/apoptotic-positive tumor and all the tumor nuclei for subsequent counting
      and calculations of proliferation and apoptotic indices.

PMID- 11457936
TI  - The role of mast cell tryptase in neoangiogenesis of premalignant and malignant
      lesions of the uterine cervix.
AB  - Recently, mast cell tryptase has been identified as another potent proangiogenic
      factor in tumors, along with fibroblast and vascular endothelial growth factors.
      Its role has been studied in a number of cancers, including carcinoma of the
      uterine cervix, with discordant results. Our aim was to study the expression of
      tryptase and bFGF in mast cells (MCs) during development of neoangiogenesis in
      premalignant and malignant lesions of the cervix. Biopsy specimens from 21
      patients without cancer and from 63 patients with dysplasias and squamous cell
      carcinomas were used. They were stained with Alcian blue-safranin O (ABSO) and
      immunostained with specific antibodies against factor VIII, CD105, tryptase, and
      bFGF. Tryptase-positive mast cells increased with tumor progression and were
      close to newly formed blood vessels. Vascularization showed a linear increase
      from dysplasia to invasive cancer. We suggest that MC tryptase may upregulate
      neoangiogenesis in carcinogenesis of the uterine cervix.

PMID- 11457937
TI  - New molecular approaches to tissue analysis.
AB  - The completion of the Human Genome Project will produce new opportunities for
      analysis of genes and their products in human tissue. The emergence of new
      technologies will enable investigators to directly examine human tissues for gene
      deletion, transposition, and amplification. In addition, we will be able to
      assess the complete gene expression of a tissue by examining the mRNA species
      using microarray chips. The emerging technologies of laser capture
      microdissection and RNA amplification enables these procedures to be carried out
      on groups of a few hundred cells, which will facilitate the examination of
      heterogeneous lesions. Finally, the application of tissue arrays and the
      capability of obtaining protein sequences in samples of only a few femtomoles of
      protein using desorption mass spectroscopy will revolutionize the analysis of
      protein expression.

PMID- 11457938
TI  - Distribution of map2 in hippocampus and cerebellum of young and old rats by
      quantitative immunohistochemistry.
AB  - The microtubule-associated protein MAP2 is a cytoskeletal protein that plays a
      regulatory role in neuronal plasticity and in maintaining the morphology of
      differentiated neurons. MAP2 distribution was assessed in hippocampus and
      cerebellum of young and old rats by quantitative immunohistochemistry. In old vs
      young rats, densitometric analysis showed a significant decrease of MAP2
      immunoreactivity in the hippocampus CA1 field (-93%), whereas no difference was
      found in cerebellar MAP2 distribution. These preliminary data suggest that in
      areas of the brain involved in memory acquisition and consolidation, MAP2
      dependent neuroplasticity and structural integrity are significantly decreased in
      aging.

PMID- 11457941
TI  - Government research program administrator. a nontraditional career for a phd
      plant biologist.

PMID- 11457942
TI  - Silencing on the spot. Induction and suppression of RNA silencing in the
      Agrobacterium-mediated transient expression system.
AB  - The Agrobacterium-mediated transient expression assay in intact tissues has
      emerged as a rapid and useful method to analyze genes and gene products in
      plants. In many cases, high levels of active protein can be produced without the
      need to produce transgenic plants. In this study, a series of tools were
      developed to enable strong or weak induction of RNA silencing and to suppress RNA
      silencing in the absence of stable transgenes. Transient delivery of a gene
      directing production of a double-stranded green fluorescent protein (GFP)
      transcript rapidly induced RNA silencing of a codelivered GFP reporter gene,
      effectively preventing accumulation of GFP protein and mRNA. RNA silencing
      triggered by the strong dsGFP inducer was partially inhibited by the tobacco etch
      virus silencing suppressor, P1/HC-Pro. In the absence of the strong double
      stranded GFP inducer, the functional GFP gene served as a weak RNA silencing
      inducer in the transient assay, severely limiting accumulation of the GFP mRNA
      over time. The weak silencing induced by the GFP gene was suppressed by P1/HC
      Pro. These results indicate RNA silencing can be triggered by a variety of
      inducers and analyzed entirely using transient gene delivery systems. They also
      indicate that RNA silencing may be a significant limitation to expression of
      genes in the Agrobacterium-mediated transient assay but that this limitation can
      be overcome by using RNA silencing suppressors.

PMID- 11457943
TI  - A large family of genes that share homology with CLAVATA3.

PMID- 11457944
TI  - Genomic computing. Explanatory analysis of plant expression profiling data using
      machine learning.

PMID- 11457945
TI  - United kingdoms.

PMID- 11457946
TI  - Cellular and subcellular localization of S-adenosyl-L-methionine:benzoic acid
      carboxyl methyltransferase, the enzyme responsible for biosynthesis of the
      volatile ester methylbenzoate in snapdragon flowers.
AB  - The benzenoid ester, methylbenzoate is one of the most abundant scent compounds
      detected in the majority of snapdragon (Antirrhinum majus) varieties. It is
      produced in upper and lower lobes of petals by enzymatic methylation of benzoic
      acid in the reaction catalyzed by S-adenosyl-L-methionine:benzoic acid carboxyl
      methyltransferase (BAMT). To identify the location of methylbenzoate
      biosynthesis, we conducted an extensive immunolocalization study by light and
      electron microscopy at cellular and subcellular levels using antibodies against
      BAMT protein. BAMT was immunolocalized predominantly in the conical cells of the
      inner epidermal layer and, to a much lesser extent, in the cells of the outer
      epidermis of snapdragon flower petal lobes. It was also located in the inner
      epidermis of the corolla tube with little BAMT protein detected in the outer
      epidermis and in the yellow hairs within the tube on the bee's way to the nectar.
      These results strongly suggest that scent biosynthetic genes are expressed almost
      exclusively in the epidermal cells of floral organs. Immunogold labeling studies
      reveal that BAMT is a cytosolic enzyme, suggesting cytosolic location of
      methylbenzoate biosynthesis. The concentration of scent production on flower
      surfaces that face the pollinators during landing may increase pollination
      efficiency and also help to minimize the biosynthetic cost of advertising for
      pollinators.

PMID- 11457947
TI  - Production of dwarf lettuce by overexpressing a pumpkin gibberellin 20-oxidase
      gene.
AB  - We investigated the effect of overexpressing a pumpkin gibberellin (GA) 20
      oxidase gene encoding an enzyme that forms predominantly biologically inactive
      products on GA biosynthesis and plant morphology in transgenic lettuce (Lactuca
      sativa cv Vanguard) plants. Lettuce was transformed with the pumpkin GA 20
      oxidase gene downstream of a strong constitutive promoter cassette (El2-35S
      Omega). The transgenic plants in which the pumpkin gene was detected by
      polymerase chain reaction were dwarfed in the T(2) generation, whereas
      transformants with a normal growth phenotype did not contain the transgene. The
      result of Southern-blot analysis showed that the transgene was integrated as a
      single copy; the plants segregated three dwarfs to one normal in the T(2)
      generation, indicating that the transgene was stable and dominant. The endogenous
      levels of GA(1) and GA(4) were reduced in the dwarfs, whereas large amounts of
      GA(17) and GA(25), which are inactive products of the pumpkin GA 20-oxidase,
      accumulated in these lines. These results indicate that a functional pumpkin GA
      20-oxidase is expressed in the transgenic lettuce, resulting in a diversion of
      the normal pathway of GA biosynthesis to inactive products. Furthermore, this
      technique may be useful for controlling plant stature in other agricultural and
      horticultural species.

PMID- 11457948
TI  - Cysteine synthase overexpression in tobacco confers tolerance to sulfur
      containing environmental pollutants.
AB  - Cysteine (Cys) synthase [O-acetyl-L-Ser(thiol)-lyase, EC 4.2.99.8; CSase] is
      responsible for the final step in biosynthesis of Cys. Transgenic tobacco
      (Nicotiana tabacum; F(1)) plants with enhanced CSase activities in the cytosol
      and in the chloroplasts were generated by cross-fertilization of two
      transformants expressing cytosolic CSase or chloroplastic CSase. The F(1)
      transgenic plants were highly tolerant to toxic sulfur dioxide and sulfite. Upon
      fumigation with 0.1 microL L(-1) sulfur dioxide, the Cys and glutathione contents
      in leaves of F(1) plants were increased significantly, but not in leaves of non
      transformed control plants. Furthermore, the leaves of F(1) plants exhibited the
      increased resistance to paraquat, a herbicide generating active oxygen species.

PMID- 11457949
TI  - The experimental herbicide CGA 325'615 inhibits synthesis of crystalline
      cellulose and causes accumulation of non-crystalline beta-1,4-glucan associated
      with CesA protein.
AB  - Developing cotton (Gossypium hirsutum) fibers, cultured in vitro with their
      associated ovules, were used to compare the effects of two herbicides that
      inhibit cellulose synthesis: 2,6-dichlorobenzonitrile (DCB) and an experimental
      thiatriazine-based herbicide, CGA 325'615. CGA 325'615 in nanomolar
      concentrations or DCB in micromolar concentrations causes inhibition of synthesis
      of crystalline cellulose. Unlike DCB, CGA 325'615 also causes concomitant
      accumulation of non-crystalline beta-1,4-glucan that can be at least partially
      solubilized from fiber walls with ammonium oxalate. The unusual solubility of
      this accumulated glucan may be explained by its strong association with protein.
      Treatment of the glucan fraction with protease changes its size distribution and
      leads to precipitation of the glucan. Treatment of the glucan fraction with
      cellulase digests the glucan and also releases protein that has been
      characterized as GhCesA-1 and GhCesA-2--proteins that are believed to represent
      the catalytic subunit of cellulose synthase. The fact that cellulase treatment is
      required to release this protein indicates an extremely tight association of the
      glucan with the CesA proteins. In addition, CGA 325'615, but not DCB, also causes
      accumulation of CesA protein and a membrane-associated cellulase in the membrane
      fraction of fibers. In addition to the effects of CGA 325'615 on levels of both
      of these proteins, the level of both also shows coordinate regulation during
      fiber development, further suggesting they are both important for cellulose
      synthesis. The accumulation of non-crystalline glucan caused by CGA 325'615
      mimics the phenotype of the cellulose-deficient rsw1 mutant of Arabidopsis that
      also accumulates an apparently similar glucan (T. Arioli, L. Peng, A.S. Betzner,
      J. Burn, W. Wittke, W. Herth, C. Camilleri, H. Hofte, J. Plazinski, R. Birch et
      al. [1998] Science 279: 717).

PMID- 11457950
TI  - Ozone quenching properties of isoprene and its antioxidant role in leaves.
AB  - Isoprene is formed in and emitted by plants and the reason for this apparent
      carbon waste is still unclear. It has been proposed that isoprene stabilizes cell
      and particularly chloroplast thylakoid membranes. We tested if membrane
      stabilization or isoprene reactivity with ozone induces protection against acute
      ozone exposures. The reduction of visible, physiological, anatomical, and
      ultrastructural (chloroplast) damage shows that clones of plants sensitive to
      ozone and unable to emit isoprene become resistant to acute and short exposure to
      ozone if they are fumigated with exogenous isoprene, and that isoprene-emitting
      plants that are sensitive to ozone do not suffer damage when exposed to ozone.
      Isoprene-induced ozone resistance is associated with the maintenance of
      photochemical efficiency and with a low energy dissipation, as indicated by
      fluorescence quenching. This suggests that isoprene effectively stabilizes
      thylakoid membranes. However, when isoprene reacts with ozone within the leaves
      or in a humid atmosphere, it quenches the ozone concentration to levels that are
      less or non-toxic for plants. Thus, protection from ozone in plants fumigated
      with isoprene may be due to a direct ozone quenching rather than to an induced
      resistance at membrane level. Irrespective of the mechanism, isoprene is one of
      the most effective antioxidants in plants.

PMID- 11457951
TI  - Increased cysteine biosynthesis capacity of transgenic tobacco overexpressing an
      O-acetylserine(thiol) lyase modifies plant responses to oxidative stress.
AB  - O-Acetylserine(thiol) lyase (OASTL), a key enzyme of plant sulfur metabolism,
      catalyzes the formation of Cys from sulfide and O-acetylserine. The biosynthesis
      of Cys is regarded as the exclusive function of sulfur reduction in plants, and a
      key limiting step in the production of glutathione (GSH), a thiol implicated in
      various cellular functions, including sulfur transport, gene expression,
      scavenging of reactive oxygen species (ROS), and resistance to biotic and abiotic
      stresses. To examine whether an increased capacity for cysteine (Cys)
      biosynthesis alters cellular responses to such stresses, we studied the
      differential changes in thiol levels and ROS scavenging of transgenic tobacco
      (Nicotiana tabacum) plants expressing the wheat (Triticum aestivum) OASTL gene,
      cys1, to SO(2) and to the ROS generator, methyl viologen. Intracellular Cys and
      GSH contents were generally higher in cys1 transgenics than in controls under
      normal growth conditions, but became especially elevated in transgenic plants
      after SO(2) exposure. An examination of differences in the ROS scavenging system
      of the transgenic plants also demonstrated the specific accumulation of Cu/Zn
      superoxide dismutase transcripts, known to be induced by Cys or GSH, and elevated
      cellular superoxide dismutase activities. The transgenic plants accordingly
      showed dramatic reductions in the extent of both foliar and photooxidative damage
      in response to acute SO(2), as well as reduced levels of chlorosis and membrane
      damage following methyl viologen treatment. Overall, our results imply that OASTL
      plays a pivotal role in the synthesis of Cys and GSH that are required for
      regulation of plant responses to oxidative stress.

PMID- 11457952
TI  - Phenol-oxidizing peroxidases contribute to the protection of plants from
      ultraviolet radiation stress.
AB  - We have studied the mechanism of UV protection in two duckweed species
      (Lemnaceae) by exploiting the UV sensitivity of photosystem II as an in situ
      sensor for radiation stress. A UV-tolerant Spirodela punctata G.F.W. Meyer
      ecotype had significantly higher indole-3-acetic acid (IAA) levels than a UV
      sensitive ecotype. Parallel work on Lemna gibba mutants suggested that UV
      tolerance is linked to IAA degradation rather than to levels of free or
      conjugated IAA. This linkage is consistent with a role for class III phenolic
      peroxidases, which have been implicated both in the degradation of IAA and the
      cross-linking of various UV-absorbing phenolics. Biochemical analysis revealed
      increased activity of a specific peroxidase isozyme in both UV-tolerant duckweed
      lines. The hypothesis that peroxidases play a role in UV protection was tested in
      a direct manner using genetically modified tobacco (Nicotiana sylvestris). It was
      found that increased activity of the anionic peroxidase correlated with increased
      tolerance to UV radiation as well as decreased levels of free auxin. We conclude
      that phenol-oxidizing peroxidases concurrently contribute to UV protection as
      well as the control of leaf and plant architecture.

PMID- 11457953
TI  - Evidence for a role of salicylic acid in the oxidative damage generated by NaCl
      and osmotic stress in Arabidopsis seedlings.
AB  - Previous studies have shown that salicylic acid (SA) is an essential component of
      the plant resistance to pathogens. We now show that SA plays a role in the plant
      response to adverse environmental conditions, such as salt and osmotic stresses.
      We have studied the responses of wild-type Arabidopsis and an SA-deficient
      transgenic line expressing a salicylate hydroxylase (NahG) gene to different
      abiotic stress conditions. Wild-type plants germinated under moderate light
      conditions in media supplemented with 100 mM NaCl or 270 mM mannitol showed
      extensive necrosis in the shoot. In contrast, NahG plants germinated under the
      same conditions remained green and developed true leaves. The lack of necrosis
      observed in NahG seedlings under the same conditions suggests that SA potentiates
      the generation of reactive oxygen species in photosynthetic tissues during salt
      and osmotic stresses. This hypothesis is supported by the following observations.
      First, the herbicide methyl viologen, a generator of superoxide radical during
      photosynthesis, produced a necrotic phenotype only in wild-type plants. Second,
      the presence of reactive oxygen-scavenging compounds in the germination media
      reversed the wild-type necrotic phenotype seen under salt and osmotic stress.
      Third, a greater increase in the oxidized state of the glutathione pool under
      NaCl stress was observed in wild-type seedlings compared with NahG seedlings.
      Fourth, greater oxidative damage occurred in wild-type seedlings compared with
      NahG seedlings under NaCl stress as measured by lipid peroxidation. Our data
      support a model for SA potentiating the stress response of the germinating
      Arabidopsis seedling.

PMID- 11457954
TI  - The delayed terminal flower phenotype is caused by a conditional mutation in the
      CENTRORADIALIS gene of snapdragon.
AB  - The snapdragon (Antirrhinum majus) centroradialis mutant (cen) is characterized
      by the development of a terminal flower, thereby replacing the normally open
      inflorescence by a closed inflorescence. In contrast to its Arabidopsis
      counterpart, terminal flower1, the cen-null mutant displays an almost constant
      number of lateral flowers below the terminal flower. Some partial revertants of
      an X-radiation-induced cen mutant showed a delayed formation of the terminal
      flower, resulting in a variable number of lateral flowers. The number of lateral
      flowers formed was shown to be environmentally controlled, with the fewer flowers
      formed under the stronger flower-inducing conditions. Plants displaying this
      "Delayed terminal flower" phenotype were found to be heterozygous for a mutant
      allele carrying a transposon in the coding region and an allele from which the
      transposon excised, leaving behind a 3-bp duplication as footprint. As a
      consequence, an iso-leucine is inserted between Asp148 and Gly149 in the
      CENTRORADIALIS protein. It is proposed that this mutation results in a low level
      of functional CEN activity, generating a phenotype that is more similar to the
      Arabidopsis Terminal flower phenotype.

PMID- 11457955
TI  - Enhanced accumulation of BiP in transgenic plants confers tolerance to water
      stress.
AB  - The binding protein (BiP) is an important component of endoplasmic reticulum
      stress response of cells. Despite extensive studies in cultured cells, a
      protective function of BiP against stress has not yet been demonstrated in whole
      multicellular organisms. Here, we have obtained transgenic tobacco (Nicotiana
      tabacum L. cv Havana) plants constitutively expressing elevated levels of BiP or
      its antisense cDNA to analyze the protective role of this endoplasmic reticulum
      lumenal stress protein at the whole plant level. Elevated levels of BiP in
      transgenic sense lines conferred tolerance to the glycosylation inhibitor
      tunicamycin during germination and tolerance to water deficit during plant
      growth. Under progressive drought, the leaf BiP levels correlated with the
      maintenance of the shoot turgidity and water content. The protective effect of
      BiP overexpression against water stress was disrupted by expression of an
      antisense BiP cDNA construct. Although overexpression of BiP prevented cellular
      dehydration, the stomatal conductance and transpiration rate in droughted sense
      leaves were higher than in control and antisense leaves. The rate of
      photosynthesis under water deficit might have caused a degree of greater osmotic
      adjustment in sense leaves because it remained unaffected during water
      deprivation, which was in marked contrast with the severe drought-induced
      decrease in the CO(2) assimilation in control and antisense leaves. In antisense
      plants, the water stress stimulation of the antioxidative defenses was higher
      than in control plants, whereas in droughted sense leaves an induction of
      superoxide dismutase activity was not observed. These results suggest that
      overexpression of BiP in plants may prevent endogenous oxidative stress.

PMID- 11457956
TI  - Role of auxin-induced reactive oxygen species in root gravitropism.
AB  - We report our studies on root gravitropism indicating that reactive oxygen
      species (ROS) may function as a downstream component in auxin-mediated signal
      transduction. A transient increase in the intracellular concentration of ROS in
      the convex endodermis resulted from either gravistimulation or unilateral
      application of auxin to vertical roots. Root bending was also brought about by
      unilateral application of ROS to vertical roots pretreated with the auxin
      transport inhibitor N-1-naphthylphthalamic acid. Furthermore, the scavenging of
      ROS by antioxidants (N-acetylcysteine, ascorbic acid, and Trolox) inhibited root
      gravitropism. These results indicate that the generation of ROS plays a role in
      root gravitropism.

PMID- 11457957
TI  - The wheat cDNA LCT1 generates hypersensitivity to sodium in a salt-sensitive
      yeast strain.
AB  - Salinity affects large areas of agricultural land, and all major crop species are
      intolerant to high levels of sodium ions. The principal route for Na(+) uptake
      into plant cells remains to be identified. Non-selective ion channels and high
      affinity potassium transporters have emerged as potential pathways for Na(+)
      entry. A third candidate for Na(+) transport into plant cells is a low-affinity
      cation transporter represented by the wheat protein LCT1, which is known to be
      permeable for a wide range of cations when expressed in yeast (Saccharomyces
      cerevisiae). To investigate the role of LCT1 in salt tolerance we have used the
      yeast strain G19, which is disrupted in the genes encoding Na(+) export pumps and
      as a result displays salt sensitivity comparable with wheat. After transformation
      with LCT1, G19 cells became hypersensitive to NaCl. We show that LCT1 expression
      results in a strong decrease of intracellular K(+)/Na(+) ratio in G19 cells due
      to the combined effect of enhanced Na(+) accumulation and loss of intracellular
      K(+). Na(+) uptake through LCT1 was inhibited by K(+) and Ca(2+) at high
      concentrations and the addition of these ions rescued growth of LCT1-transformed
      G19 on saline medium. LCT1 was also shown to mediate the uptake of Li(+) and
      Cs(+). Expression of two mutant LCT1 cDNAs with N-terminal truncations resulted
      in decreased Ca(2+) uptake and increased Na(+) tolerance compared with expression
      of the full-length LCT1. Our findings strongly suggest that LCT1 represents a
      molecular link between Ca(2+) and Na(+) uptake into plant cells.

PMID- 11457958
TI  - Differential expression of members of the annexin multigene family in
      Arabidopsis.
AB  - Although in most plant species no more than two annexin genes have been reported
      to date, seven annexin homologs have been identified in Arabidopsis, Annexin
      Arabidopsis 1-7 (AnnAt1--AnnAt7). This establishes that annexins can be a
      diverse, multigene protein family in a single plant species. Here we compare and
      analyze these seven annexin gene sequences and present the in situ RNA
      localization patterns of two of these genes, AnnAt1 and AnnAt2, during different
      stages of Arabidopsis development. Sequence analysis of AnnAt1--AnnAt7 reveals
      that they contain the characteristic four structural repeats including the more
      highly conserved 17-amino acid endonexin fold region found in vertebrate
      annexins. Alignment comparisons show that there are differences within the repeat
      regions that may have functional importance. To assess the relative level of
      expression in various tissues, reverse transcription-PCR was carried out using
      gene-specific primers for each of the Arabidopsis annexin genes. In addition,
      northern blot analysis using gene-specific probes indicates differences in AnnAt1
      and AnnAt2 expression levels in different tissues. AnnAt1 is expressed in all
      tissues examined and is most abundant in stems, whereas AnnAt2 is expressed
      mainly in root tissue and to a lesser extent in stems and flowers. In situ RNA
      localization demonstrates that these two annexin genes display developmentally
      regulated tissue-specific and cell-specific expression patterns. These patterns
      are both distinct and overlapping. The developmental expression patterns for both
      annexins provide further support for the hypothesis that annexins are involved in
      the Golgi-mediated secretion of polysaccharides.

PMID- 11457959
TI  - Analysis of flowering time control in Arabidopsis by comparison of double and
      triple mutants.
AB  - Three genetic pathways promote flowering of Arabidopsis under long photoperiods.
      These pathways are represented by the genes CO, FCA, and GA1, which act in the
      long-day, autonomous, and gibberellin pathways, respectively. To test whether
      these are the only pathways that promote flowering under long photoperiods, the
      co-2 fca-1 ga1-3 triple mutant was constructed. These plants never flowered under
      long- or short-day conditions, indicating that the three pathways impaired by
      these mutations are absolutely required for flowering under these conditions. The
      triple mutant background represents a "vegetative ground state" enabling the
      roles of single pathways to be described in the corresponding double mutants. The
      phenotypes of plants carrying all eight combinations of wild-type and mutant
      alleles at the three loci were compared under long- and short-day conditions.
      This analysis demonstrated that under long photoperiods the long-day pathway
      promoted flowering most effectively, whereas under short photoperiods the
      gibberellin pathway had the strongest effect. The autonomous pathway had a weak
      effect when acting alone under either photoperiod but appeared to play an
      important role in facilitating the promotion of flowering by the other two
      pathways. The vegetative phenotype of the triple mutant could be overcome by
      vernalization, suggesting that a fourth pathway promoted flowering under these
      conditions. These observations are discussed in light of current models
      describing the regulation of flowering time in Arabidopsis.

PMID- 11457960
TI  - The Ca(2+) status of the endoplasmic reticulum is altered by induction of
      calreticulin expression in transgenic plants.
AB  - To investigate the endoplasmic reticulum (ER) Ca(2+) stores in plant cells, we
      generated tobacco (Nicotiana tabacum; NT1) suspension cells and Arabidopsis
      plants with altered levels of calreticulin (CRT), an ER-localized Ca(2+)-binding
      protein. NT1 cells and Arabidopsis plants were transformed with a maize (Zea
      mays) CRT gene in both sense and antisense orientations under the control of an
      Arabidopsis heat shock promoter. ER-enriched membrane fractions from NT1 cells
      were used to examine how altered expression of CRT affects Ca(2+) uptake and
      release. We found that a 2.5-fold increase in CRT led to a 2-fold increase in ATP
      dependent (45)Ca(2+) accumulation in the ER-enriched fraction compared with heat
      shocked wild-type controls. Furthermore, after treatment with the Ca(2+)
      ionophore ionomycin, ER microsomes from NT1 cells overproducing CRT showed a 2
      fold increase in the amount of (45)Ca(2+) released, and a 2- to 3-fold increase
      in the amount of (45)Ca(2+) retained compared with wild type. These data indicate
      that altering the production of CRT affects the ER Ca(2+) pool. In addition, CRT
      transgenic Arabidopsis plants were used to determine if altered CRT levels had
      any physiological effects. We found that the level of CRT in heat shock-induced
      CRT transgenic plants correlated positively with the retention of chlorophyll
      when the plants were transferred from Ca(2+)-containing medium to Ca(2+)-depleted
      medium. Together these data are consistent with the hypothesis that increasing
      CRT in the ER increases the ER Ca(2+) stores and thereby enhances the survival of
      plants grown in low Ca(2+) medium.

PMID- 11457961
TI  - An Arabidopsis mutant tolerant to lethal ultraviolet-B levels shows
      constitutively elevated accumulation of flavonoids and other phenolics.
AB  - The isolation and characterization of mutants hypersensitive to ultraviolet (UV)
      radiation has been a powerful tool to learn about the mechanisms that protect
      plants against UV-induced damage. To increase our understanding of the various
      mechanisms of defense against UVB radiation, we searched for mutations that would
      increase the level of tolerance of Arabidopsis plants to UV radiation. We
      describe a single gene dominant mutation (uvt1) that leads to a remarkable
      tolerance to UVB radiation conditions that would kill wild-type plants. Pigment
      analyses show a constitutive increase in accumulation of UV-absorbing compounds
      in uvt1 that increases the capacity of the leaves to block UVB radiation and
      therefore is likely to be responsible for the elevated resistance of this mutant
      to UVB radiation. These increases in absorption in the UV region are due, at
      least in part, to increases in flavonoid and sinapate accumulation. Expression of
      chalcone synthase (CHS) mRNA was shown to be constitutively elevated in uvt1
      plants, suggesting that the increases in absorption may be a consequence of
      changes in gene expression. Expression of CHS in uvt1 was shown to be still
      inducible by UV, indicating that the uvt1 lesion may not affect the UV-mediated
      regulation of CHS gene expression. Our data support an important role for UV
      screens in the overall protection of plants to UVB radiation. The uvt1 mutant
      could prove to be an important tool to elucidate further the exact role of UV
      absorbing pigments in UV protection as well as the relative contribution of other
      mechanisms to the overall tolerance of plants to UV radiation.

PMID- 11457962
TI  - Expression and chloroplast targeting of cholesterol oxidase in transgenic tobacco
      plants.
AB  - Cholesterol oxidase represents a novel type of insecticidal protein with potent
      activity against the cotton boll weevil (Anthonomus grandis grandis Boheman). We
      transformed tobacco (Nicotiana tabacum) plants with the cholesterol oxidase choM
      gene and expressed cytosolic and chloroplast-targeted versions of the ChoM
      protein. Transgenic leaf tissues expressing cholesterol oxidase exerted
      insecticidal activity against boll weevil larvae. Our results indicate that
      cholesterol oxidase can metabolize phytosterols in vivo when produced
      cytosolically or when targeted to chloroplasts. The transgenic plants exhibiting
      cytosolic expression accumulated low levels of saturated sterols known as
      stanols, and displayed severe developmental aberrations. In contrast, the
      transgenic plants expressing chloroplast-targeted cholesterol oxidase maintained
      a greater accumulation of stanols, and appeared phenotypically and
      developmentally normal. These results are discussed within the context of plant
      sterol distribution and metabolism.

PMID- 11457963
TI  - An insight into cell elasticity and load-bearing ability. Measurement and theory.
AB  - We have studied the elasticity and load bearing ability of plant tissue at the
      cellular level, using onion (Allium cepa) epidermal cells. The Young's modulus
      and Poisson's ratio of the cells were obtained by loading a tensile force on
      onion epidermal peels of different turgor pressures, and measuring the elongation
      and the lateral contraction of the peels. The Young's moduli and the Poisson's
      ratios ranged from 3.5 to 8.0 MPa and 0.18 to 0.30, respectively. To determine
      the effects of cell elasticity and turgor pressure on the cell's ability to bear
      load, we loaded a small glass ball onto a cell and measured the projected contact
      area between the ball and the cell. Unlike previous studies, we considered the
      cell as a whole entity, and utilized the Boussinesq's solution to derive the
      relevant equations that related the elastic parameters and cell deformation. For
      cells with a turgor pressure > or = 0.34 MPa, the predicted contact area agreed
      well with the measured area. The equations could also predict cell turgor
      pressure with a deviation from the measured value of 0.01 MPa. This study gives
      strong support to ball tonometry, a new method of measuring cell turgor pressure.

PMID- 11457964
TI  - NAD malic enzyme and the control of carbohydrate metabolism in potato tubers.
AB  - Potato (Solanum tuberosum) plants were transformed with a cDNA encoding the 59-kD
      subunit of the potato tuber NAD-dependent malic enzyme (NADME) in the antisense
      orientation. Measurements of the maximum catalytic activity of NADME in tubers
      revealed a range of reductions in the activity of this enzyme down to 40% of wild
      type activity. There were no detrimental effects on plant growth or tuber yield.
      Biochemical analyses of developing tubers indicated that a reduction in NADME
      activity had no detectable effects on flux through the tricarboxylic acid cycle.
      However, there was an effect on glycolytic metabolism with significant increases
      in the concentration of 3-phosphoglycerate and phosphoenolpyruvate. These results
      suggest that alterations in the levels of intermediates toward the end of the
      glycolytic pathway may allow respiratory flux to continue at wild-type rates
      despite the reduction in NADME. There was also a statistically significant
      negative correlation between NADME activity and tuber starch content, with tubers
      containing reduced NADME having an increased starch content. The effect on
      plastid metabolism may result from the observed glycolytic perturbations.

PMID- 11457965
TI  - Inhibition of proteasome activity strongly affects kiwifruit pollen germination.
      Involvement of the ubiquitin/proteasome pathway as a major regulator.
AB  - The 26S proteasome is a multicatalytic complex that acts as primary protease of
      the ubiquitin-mediated proteolytic pathway in eukaryotes. We provide here the
      first evidence that the proteasome plays a key role in regulating pollen tube
      growth. Immunoblotting experiments revealed the presence of high levels of free
      ubiquitin and ubiquitin conjugates in rehydrated and germinating pollen of
      kiwifruit [Actinidia deliciosa var. deliciosa (A. Chev) C. F. Liang et A. R.
      Ferguson]. Proteasome activity, assayed fluorometrically, accompanied the
      progression of germination. Specific inhibitors of proteasome function such as
      benzyloxycarbonyl-leucinyl-leucinyl-leucinal (MG-132), clasto-lactacystin beta
      lactone, and epoxomicin significantly decreased tube growth or altered tube
      morphology. High-molecular mass, ubiquitinated proteins accumulated in MG-132-
      and beta-lactone-treated pollen, indicating that proteasome function was
      effectively impaired. The inhibitors were also able to decrease in vitro
      proteasome activity in pollen extracts. Because MG-132 can inhibit calpains, as
      well as the proteasome, trans-epoxy succinyl-L-leucylamido-(4-guanidino) butane
      (E-64), an inhibitor of cysteine proteases, was investigated. Some reduction in
      tube growth rate was observed, but only at 80 microM E-64, and no abnormal tubes
      were produced. Furthermore, no inhibition of tube growth was observed when
      another inhibitor of cysteine proteases, leupeptin, or inhibitors of serine and
      aspartic proteases (phenylmethylsulfonyl fluoride and pepstatin) were used. Our
      results indicate that protein turnover during tube organization and elongation in
      kiwifruit pollen is important, and our results also implicate the ubiquitin/26S
      proteasome as the major proteolytic pathway involved.

PMID- 11457966
TI  - Binding site for chitin oligosaccharides in the soybean plasma membrane.
AB  - Affinity cross-linking of the plasma membrane fraction to an (125)I-labeled
      chitin oligosaccharide led to the identification and characterization of an 85
      kD, chitin binding protein in plasma membrane-enriched fractions from both
      suspension-cultured soybean cells and root tissue. Inhibition analysis indicated
      a binding preference for larger (i.e. degrees of polymerization = 8) N-acetylated
      chitin molecules with a 50% inhibition of initial activity value of approximately
      50 nM. N-Acetyl-glucosamine and chitobiose showed no inhibitory effects at
      concentrations as high as 250 microM. It is noteworthy that the major lipo-chitin
      oligosaccharide Nod signal produced by Bradyrhizobium japonicum was also shown to
      be a competitive inhibitor of ligand binding. However, the binding site appeared
      to recognize the chitin portion of the Nod signal, and it is unlikely that this
      binding activity represents a specific Nod signal receptor. Chitooligosaccharide
      specificity for induction of medium alkalinization and the generation of reactive
      oxygen in suspension-cultured cells paralleled the binding activity. Taken
      together, the presence of the chitin binding protein in the plasma membrane
      fraction and the specificity and induction of a biological response upon ligand
      binding suggest a role for the protein as an initial response mechanism for
      chitin perception in soybean (Glycine max).

PMID- 11457967
TI  - Altered expression of SPINDLY affects gibberellin response and plant development.
AB  - Gibberellins (GAs) are plant hormones with diverse roles in plant growth and
      development. SPINDLY (SPY) is one of several genes identified in Arabidopsis that
      are involved in GA response and it is thought to encode an O-GlcNAc transferase.
      Genetic analysis suggests that SPY negatively regulates GA response. To test the
      hypothesis that SPY acts specifically as a negatively acting component of GA
      signal transduction, spy mutants and plants containing a 35S:SPY construct have
      been examined. A detailed investigation of the spy mutant phenotype suggests that
      SPY may play a role in plant development beyond its role in GA signaling.
      Consistent with this suggestion, the analysis of spy er plants suggests that the
      ERECTA (ER) gene, which has not been implicated as having a role in GA signaling,
      appears to enhance the non-GA spy mutant phenotypes. Arabidopsis plants
      containing a 35S:SPY construct possess reduced GA response at seed germination,
      but also possess phenotypes consistent with increased GA response, although not
      identical to spy mutants, during later vegetative and reproductive development.
      Based on these results, the hypothesis that SPY is specific for GA signaling is
      rejected. Instead, it is proposed that SPY is a negative regulator of GA response
      that has additional roles in plant development.

PMID- 11457968
TI  - Defoliation induces fructan 1-exohydrolase II in Witloof chicory roots. Cloning
      and purification of two isoforms, fructan 1-exohydrolase IIa and fructan 1
      exohydrolase IIb. Mass fingerprint of the fructan 1-exohydrolase II enzymes.
AB  - The cloning of two highly homologous chicory (Cichorium intybus var. foliosum cv
      Flash) fructan 1-exohydrolase cDNAs (1-FEH IIa and 1-FEH IIb) is described. Both
      isoenzymes could be purified from forced chicory roots as well as from the
      etiolated "Belgian endive" leaves where the 1-FEH IIa isoform is present in
      higher concentrations. Full-length cDNAs were obtained by a combination of
      reverse transcriptase-polymerase chain reaction (PCR), PCR and 5'- and 3'-rapid
      amplification of cDNA ends using primers based on N-terminal and conserved amino
      acid sequences. 1-FEH IIa and 1-FEH IIb cDNA-derived amino acid sequences are
      most homologous to a new group of plant glycosyl hydrolases harboring cell wall
      type enzymes with acid isoelectric points. Unlike the observed expression
      profiles of chicory 1-FEH I, northern analysis revealed that 1-FEH II is
      expressed when young chicory plants are defoliated, suggesting that this enzyme
      can be induced at any developmental stage when large energy supplies are
      necessary (regrowth after defoliation).

PMID- 11457969
TI  - Nitric oxide induces stomatal closure and enhances the adaptive plant responses
      against drought stress.
AB  - Nitric oxide (NO) is a very active molecule involved in many and diverse
      biological pathways where it has proved to be protective against damages provoked
      by oxidative stress conditions. In this work, we studied the effect of two NO
      donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine SNP
      treated on the response of wheat (Triticum aestivum) to water stress conditions.
      After 2 and 3 h of drought, detached wheat leaves pretreated with 150 microM SNP
      retained up to 15% more water than those pretreated with water or NO(2)(-)/NO(3)(
      ). The effect of SNP treatment on water retention was also found in wheat
      seedlings after 7 d of drought. These results were consistent with a 20% decrease
      in the transpiration rate of SNP-treated detached wheat leaves for the same
      analyzed time. In parallel experiments, NO was also able to induce a 35%, 30%,
      and 65% of stomatal closure in three different species, Tradescantia sp.
      (monocotyledonous) and two dicotyledonous, Salpichroa organifolia and fava bean
      (Vicia faba), respectively. In SNP-treated leaves of Tradescantia sp., the
      stomatal closure was correlated with a 10% increase on RWC. Ion leakage, a cell
      injury index, was 25% lower in SNP-treated wheat leaves compared with control
      ones after the recovery period. Carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide), a specific NO scavenger, reverted SNP
      action by restoring the transpiration rate, stomatal aperture, and the ion
      leakage to the level found in untreated leaves. Northern-blot analysis showed
      that SNP-treated wheat leaves display a 2-fold accumulation of a group three late
      embryogenesis abundant transcript with respect to control leaves both after 2 and
      4 h of drought periods. All together, these results suggest that the exogenous
      application of NO donors might confer an increased tolerance to severe drought
      stress conditions in plants.

PMID- 11457970
TI  - Mutational analysis of branching in pea. Evidence that Rms1 and Rms5 regulate the
      same novel signal.
AB  - The fifth increased branching ramosus (rms) mutant, rms5, from pea (Pisum
      sativum), is described here for phenotype and grafting responses with four other
      rms mutants. Xylem sap zeatin riboside concentration and shoot auxin levels in
      rms5 plants have also been compared with rms1 and wild type (WT). Rms1 and Rms5
      appear to act closely at the biochemical or cellular level to control branching,
      because branching was inhibited in reciprocal epicotyl grafts between rms5 or
      rms1 and WT plants, but not inhibited in reciprocal grafts between rms5 and rms1
      seedlings. The weakly transgressive or slightly additive phenotype of the rms1
      rms5 double mutant provides further evidence for this interaction. Like rms1,
      rms5 rootstocks have reduced xylem sap cytokinin concentrations, and rms5 shoots
      do not appear deficient in indole-3-acetic acid or 4-chloroindole-3-acetic acid.
      Rms1 and Rms5 are similar in their interaction with other Rms genes. Reciprocal
      grafting studies with rms1, rms2, and rms5, together with the fact that root
      xylem sap cytokinin concentrations are reduced in rms1 and rms5 and elevated in
      rms2 plants, indicates that Rms1 and Rms5 may control a different pathway than
      that controlled by Rms2. Our studies indicate that Rms1 and Rms5 may regulate a
      novel graft-transmissible signal involved in the control of branching.

PMID- 11457971
TI  - Cell cycle regulation of cyclin-dependent kinases in tobacco cultivar Bright
      Yellow-2 cells.
AB  - Plants possess two major classes of cyclin-dependent kinases (CDK) with cyclin
      binding motifs PSTAIRE (CDK-a) and PPTA/TLRE (CDK-b). Tobacco (Nicotiana tabacum
      L. cv Bright Yellow-2) cells are the most highly synchronizable plant culture,
      but no detailed analysis of CDK activities has been reported in this system. Here
      we describe isolation of new PPTALRE CDKs (Nicta;CdkB1) from Bright Yellow-2
      cells and present detailed analysis of the mRNA, protein and kinase activity
      levels of CdkB1, and the PSTAIRE CDKA during the growth and cell cycles. CdkA and
      CdkB1 transcripts are more abundant in exponential than in stationary phase
      cells, but the two genes show strikingly different regulation during the cell
      cycle. CdkA mRNA and protein accumulate during G1 in cells re-entering the cell
      cycle, and immunoprecipitated histone H1 kinase activity increases at the G1/S
      boundary. Aphidicolin synchronized cells show the highest CDKA-associated histone
      H1 kinase activity during S-G2 phases, although CdkA mRNA and protein levels are
      not significantly regulated. In contrast, CdkB1 transcripts are present at very
      low levels until S phase and CDKB1 protein and kinase activity is almost
      undetectable in G1. CdkB1 mRNA accumulates through S until M phase and its
      associated kinase activity peaks at the G2/M boundary, confirming that
      transcription of PPTALRE CDKs is cell cycle regulated. We suggest that CDKA
      kinase activity likely plays roles at the G1/S phase boundary, during S phase,
      and at the G2/M phase transition, and that CDKB1 kinase activity is present only
      at G2/M.

PMID- 11457972
TI  - Cytokinin overproducing ove mutants of Physcomitrella patens show increased
      riboside to base conversion.
AB  - Ove mutants in the moss Physcomitrella patens can arise from different recessive
      mutations. These mutants display a much larger number of buds than the wild type
      (wt) due to a dramatic overproduction of cytokinins (Cks), which are released
      into the culture medium (T.L. Wang, R. Horgan, D.J. Cove [1981] Plant Physiol 68:
      735-738). The amounts of isopentenyladenine (iP) and isopentenyladenosine
      ([9R]iP) produced by chloronema of different ove mutants were measured. Levels of
      the major Ck iP in the culture medium of the mutants oveA78, oveA201, oveC200,
      and oveB300 (cultured at 21 degrees C) were 4-fold (oveA78) to 22-fold (oveB300)
      higher than for the wt. A new temperature-sensitive ove strain oveST25, which
      exhibits a strong ove phenotype at 25 degrees C, was also studied. It produced
      about 260 times more iP than the thiamine auxotrophic wt from which it was
      derived. To contribute to the physiological understanding of Ck overproduction,
      in vivo labeling experiments with (3)H-[9R]iP were performed. In all ove mutants
      analyzed, the rate of (3)H-[9R]iP conversion to (3)H-iP was higher as compared
      with the wt. In oveST25, the 3-fold increased riboside to base conversion was
      temperature inducible and correlated with the iP production. Analysis of Ck
      catabolism revealed no major differences between ove mutants and wt, thus
      indicating that ove mutants are unlikely to be degradation mutants. The data
      suggest that in ove mutants the increased riboside to base conversion is part of
      a generally up-regulated Ck biosynthetic pathway and may play an important role
      for the enhanced release of iP into the medium.

PMID- 11457973
TI  - Ethylene induces antifreeze activity in winter rye leaves.
AB  - Antifreeze activity is induced by cold temperatures in winter rye (Secale
      cereale) leaves. The activity arises from six antifreeze proteins that accumulate
      in the apoplast of winter rye leaves during cold acclimation. The individual
      antifreeze proteins are similar to pathogenesis-related proteins, including
      glucanases, chitinases, and thaumatin-like proteins. The objective of this study
      was to study the regulation of antifreeze activity in response to ethylene and
      salicyclic acid, which are known regulators of pathogenesis-related proteins
      induced by pathogens. Nonacclimated plants treated with salicylic acid
      accumulated apoplastic proteins with no antifreeze activity. In contrast, when
      nonacclimated plants were exposed to ethylene, both antifreeze activity and the
      concentration of apoplastic protein increased in rye leaves. Immunoblotting
      revealed that six of the seven accumulated apoplastic proteins consisted of two
      glucanases, two chitinases, and two thaumatin-like proteins. The ethylene
      releasing agent ethephon and the ethylene precursor 1-aminocyclopropane-1
      carboxylate also induced high levels of antifreeze activity at 20 degrees C, and
      this effect could be blocked by the ethylene inhibitor AgNO(3). When intact rye
      plants were exposed to 5 degrees C, endogenous ethylene production and antifreeze
      activity were detected within 12 and 48 h of exposure to cold, respectively. Rye
      plants exposed to drought produced both ethylene and antifreeze activity within
      24 h. We conclude that ethylene is involved in regulating antifreeze activity in
      winter rye in response to cold and drought.

PMID- 11457974
TI  - beta-Alanine betaine synthesis in the Plumbaginaceae. Purification and
      characterization of a trifunctional, S-adenosyl-L-methionine-dependent N
      methyltransferase from Limonium latifolium leaves.
AB  - beta-Alanine (beta-Ala) betaine is an osmoprotective compound accumulated by most
      members of the highly stress-tolerant family Plumbaginaceae. Its potential role
      in plant tolerance to salinity and hypoxia makes its synthetic pathway an
      interesting target for metabolic engineering. In the Plumbaginaceae, beta-Ala
      betaine is synthesized by S-adenosyl-L-methionine-dependent N-methylation of beta
      Ala via N-methyl beta-Ala and N,N-dimethyl beta-Ala. It was not known how many N
      methyltransferases (NMTases) participate in the three N-methylations of beta-Ala.
      An NMTase was purified about 1,890-fold, from Limonium latifolium leaves, using a
      protocol consisting of polyethylene glycol precipitation, heat treatment, anion
      exchange chromatography, gel filtration, native polyacrylamide gel
      electrophoresis, and two substrate affinity chromatography steps. The purified
      NMTase was trifunctional, methylating beta-Ala, N-methyl beta-Ala, and N,N
      dimethyl beta-Ala. Gel filtration and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analyses indicated that the native NMTase is a dimer of 43-kD
      subunits. The NMTase had an apparent K(m) of 45 microM S-adenosyl-l-methionine
      and substrate inhibition was observed above 200 microM. The apparent K(m) values
      for the methyl acceptor substrates were 5.3, 5.7, and 5.9 mM for beta-Ala, N
      methyl beta-Ala, and N,N-dimethyl beta-Ala, respectively. The NMTase had an
      isoelectric point of 5.15 and was reversibly inhibited by the thiol reagent p
      hydroxymercuribenzoic acid.

PMID- 11457975
TI  - Ectopic expression of the tetratricopeptide repeat domain of SPINDLY causes
      defects in gibberellin response.
AB  - The SPINDLY (SPY) protein of Arabidopsis is a negative regulator of gibberellin
      (GA) response. The SPY protein has 10 copies of the tetratricopeptide repeat
      (TPR) at the N terminus. TPR motifs function as protein-protein interaction
      domains. Several spy alleles are affected only in the TPR region suggesting that
      protein-protein interactions mediated by this domain are important for proper GA
      signaling. We have used a reverse genetics approach to further investigate the
      role of the TPR domain. The TPR domain of SPY was overexpressed in wild-type,
      gai, and spy plants. Expression of the TPR domain alone is not sufficient to
      rescue spy mutants. Expression of the TPR domain in a wild-type background
      produces phenotypes similar to those caused by loss-of-function spy mutants
      including resistance to GA biosynthesis inhibitors, short hypocotyl length, and
      early flowering. The dwarfing of the floral shoot internodes caused by the gai
      mutation was suppressed by expression of the TRP domain. Expression of the TPR
      domain had no effect on the abundance of endogenous SPY mRNA. The TPR domain was
      found to interact with SPY both in vitro and in yeast two-hybrid assays. These
      data indicate that the TPR domain of SPY can participate in protein-protein
      interactions and that these interactions are important for the proper functioning
      of SPY.

PMID- 11457976
TI  - Fatty acid synthesis in pea root plastids is inhibited by the action of long
      chain acyl- coenzyme as on metabolite transporters.
AB  - The uptake in vitro of glucose (Glc)-6-phosphate (Glc-6-P) into plastids from the
      roots of 10- to 14-d-old pea (Pisum sativum L. cv Puget) plants was inhibited by
      oleoyl-coenzyme A (CoA) concentrations in the low micromolar range (1--2 microM).
      The IC(50) (the concentration of inhibitor that reduces enzyme activity by 50%)
      for the inhibition of Glc-6-P uptake was approximately 750 nM; inhibition was
      reversed by recombinant rapeseed (Brassica napus) acyl-CoA binding protein. In
      the presence of ATP (3 mM) and CoASH (coenzyme A; 0.3 mM), Glc-6-P uptake was
      inhibited by 60%, due to long-chain acyl-CoA synthesis, presumably from
      endogenous sources of fatty acids present in the preparations. Addition of oleoyl
      CoA (1 microM) decreased carbon flux from Glc-6-P into the synthesis of starch
      and through the oxidative pentose phosphate (OPP) pathway by up to 73% and 40%,
      respectively. The incorporation of carbon from Glc-6-P into fatty acids was not
      detected under any conditions. Oleoyl-CoA inhibited the incorporation of acetate
      into fatty acids by 67%, a decrease similar to that when ATP was excluded from
      incubations. The oleoyl-CoA-dependent inhibition of fatty acid synthesis was
      attributable to a direct inhibition of the adenine nucleotide translocator by
      oleoyl-CoA, which indirectly reduced fatty acid synthesis by ATP deprivation. The
      Glc-6-P-dependent stimulation of acetate incorporation into fatty acids was
      reversed by the addition of oleoyl-CoA.

PMID- 11457977
TI  - Mitochondrial adaptations to NaCl. Complex I is protected by anti-oxidants and
      small heat shock proteins, whereas complex II is protected by proline and
      betaine.
AB  - High soil sodium (Na) is a common stress in natural and agricultural systems.
      Roots are usually the first tissues exposed to Na stress and Na stress-related
      impairment of mitochondrial function is likely to be particularly important in
      roots. However, neither the effects of NaCl on mitochondrial function, nor its
      protection by several potential adaptive mechanisms, have been well studied. This
      study investigated the effects of NaCl stress on maize (Zea mays) mitochondrial
      electron transport and its relative protection by osmoprotectants (proline,
      betaine, and sucrose), antioxidants (ascorbate, glutathione, and alpha
      tocopherol), antioxidant enzymes (catalase and Cu/Zn-superoxide dismutase), and
      mitochondrial small heat shock proteins (sHsps). We demonstrate that Complex I
      electron transport is protected by antioxidants and sHsps, but not
      osmoprotectants, whereas Complex II is protected only by low concentrations of
      proline and betaine. These results indicate that NaCl stress damaged Complex I
      via oxidative stress and suggests that sHsps may protect Complex I as
      antioxidants, but NaCl damaged Complex II directly. This is the first study to
      demonstrate that NaCl stress differentially affects Complex I and II in plants
      and that protection of Complex I and II during NaCl stress is achieved by
      different mechanisms.

PMID- 11457978
TI  - Homo-phytochelatins are synthesized in response to cadmium in azuki beans.
AB  - In a recent report, it was claimed that azuki beans (Vigna angularis) do not
      synthesize phytochelatins (PCs) upon exposure to cadmium, although glutathione
      (GSH), the substrate for PC synthesis, is present in this plant. This legume
      species thus would be the first exception in the plant kingdom that would fail to
      complex heavy metals by PCs. Here, we report that not GSH, but only
      homoglutathione can be detected in this plant and that homo-phytochelatins are
      formed when azuki beans are challenged with heavy metals such as cadmium. We also
      show that the 5,5'-dithiobis(2-nitrobenzoic acid)-oxidized GSH reductase
      recycling assay, used for GSH quantification in the recent study of heavy metal
      tolerance in azuki beans, reacts both with GSH and homoglutathione and therefore
      cannot be used when biological samples should be analyzed exclusively for GSH.

PMID- 11457979
TI  - Superoxide production by plant homologues of the gp91(phox) NADPH oxidase.
      Modulation of activity by calcium and by tobacco mosaic virus infection.
AB  - Genes encoding homologs of the gp91(phox) subunit of the plasma membrane NADPH
      oxidase complex have been identified in plants and are hypothesized to be a
      source of reactive oxygen species during defense responses. However, the direct
      involvement of the gene products in superoxide (O(2)(-)) production has yet to be
      shown. A novel activity gel assay based on protein fractionation in native or
      sodium dodecyl sulfate (SDS)-denaturing polyacrylamide gels was developed. In
      native polyacrylamide gel electrophoresis, one or two major O(2)(-)-producing
      formazan bands were detected in tomato (Lycopersicum esculentum Mill. cv
      Moneymaker) and tobacco (Nicotiana tabacum var. Samsun, NN) plasma membranes,
      respectively. Denaturing fractionation of tomato and tobacco plasma membrane in
      SDS-polyacrylamide gel electrophoresis, followed by regeneration of the in-gel
      activity, revealed NADPH-dependent O(2)(-)-producing formazan bands of 106-, 103
      , and 80- to 75-kD molecular masses. The SDS and native activity bands were
      dependent on NADPH and completely inhibited by diphenylene iodonium or CuZn-
      O(2)(-) dismutase, indicating that the formazan precipitates were due to
      reduction by O(2)(-) radicals catalyzed by an NADPH-dependent flavin containing
      enzyme. The source of the plasma membrane activity bands was confirmed by their
      cross-reaction with antibody prepared from the C terminus of the tomato
      gp91(phox) homolog. Membrane extracts as well as the in-gel NADPH oxidase
      activities were stimulated in the presence of Ca(2+). In addition, the relative
      activity of the gp91(phox) homolog was enhanced in the plasma membrane of tobacco
      mosaic virus-infected leaves. Thus, in contrast to the mammalian gp91(phox), the
      plant homolog can produce O(2)(-) in the absence of additional cytosolic
      components and is stimulated directly by Ca(2+).

PMID- 11457980
TI  - Light-induced growth promotion by SPA1 counteracts phytochrome-mediated growth
      inhibition during de-etiolation.
AB  - Previous evidence has suggested that SPA1 is a signal transduction component that
      appears to require phytochrome A for function in seedling photomorphogenesis.
      Using digital image analysis, we examined the time course of growth inhibition
      induced by red light in spa1 mutants to test the interpretation that SPA1
      functions early in a phyA-specific signaling pathway. By comparing wild-type and
      mutant responses, we found that SPA1 caused an increase in hypocotyl growth rate
      after approximately 2 h of continuous red light, whereas the onset of phyA
      mediated inhibition was detected within several minutes. Thus, SPA1-dependent
      growth promotion began after phyA started to inhibit growth. The action of SPA1
      persisted for approximately 2 d of red light, a period well beyond the time when
      the phyA photoreceptor and its influence on growth have both decayed to
      undetectable levels. Also, SPA1 promoted growth for many hours in the complete
      absence of a light stimulus when red-light-grown seedlings were shifted to
      darkness. We propose that SPA1 functions in a light-induced mechanism that
      promotes growth and thereby counteracts growth inhibition mediated by phyA and
      phyB. Our finding that spa1 seedlings do not display growth promotion in response
      to end-of-day pulses of far-red light, even in a phyA-null background, supports
      this interpretation. Combined, these results lead us to the view that the rate of
      hypocotyl elongation in light is determined by at least two independent, opposing
      processes; an inhibition of growth by the phytochromes and a promotion of growth
      by light-activated SPA1.

PMID- 11457981
TI  - Class I beta-1,3-glucanase and chitinase are expressed in the micropylar
      endosperm of tomato seeds prior to radicle emergence.
AB  - beta-1,3-Glucanase (EC 3.2.1.39) and chitinase (EC 3.2.1.14) mRNAs, proteins, and
      enzyme activities were expressed specifically in the micropylar tissues of
      imbibed tomato (Lycopersicon esculentum Mill.) seeds prior to radicle emergence.
      RNA hybridization and immunoblotting demonstrated that both enzymes were class I
      basic isoforms. beta-1,3-Glucanase was expressed exclusively in the endosperm cap
      tissue, whereas chitinase localized to both endosperm cap and radicle tip
      tissues. beta-1,3-Glucanase and chitinase appeared in the micropylar tissues of
      gibberellin-deficient gib-1 tomato seeds only when supplied with gibberellin.
      Accumulation of beta-1,3-glucanase mRNA, protein and enzyme activity was reduced
      by 100 microM abscisic acid, which delayed or prevented radicle emergence but not
      endosperm cap weakening. In contrast, expression of chitinase mRNA, protein, and
      enzyme activity was not affected by abscisic acid. Neither of these enzymes
      significantly hydrolyzed isolated tomato endosperm cap cell walls. Although both
      beta-1,3-glucanase and chitinase were expressed in tomato endosperm cap tissue
      prior to radicle emergence, we found no evidence that they were directly involved
      in cell wall modification or tissue weakening. Possible functions of these
      hydrolases during tomato seed germination are discussed.

PMID- 11457982
TI  - Influence of growth conditions and developmental stage on N-glycan heterogeneity
      of transgenic immunoglobulin G and endogenous proteins in tobacco leaves.
AB  - Plants are regarded as a promising system for the production of heterologous
      proteins. However, little is known about the influence of plant development and
      growth conditions on N-linked glycosylation. To investigate this, transgenic
      tobacco (Nicotiana tabacum cv Samsun NN) plants expressing a mouse immunoglobulin
      G antibody (MGR48) were grown in climate rooms under four different climate
      conditions, i.e. at 15 degrees C and 25 degrees C and at either low or high light
      conditions. N-glycans on plantibodies and soluble endogenous proteins were
      analyzed with matrix-assisted laser desorption ionization-time of flight (MALDI
      TOF) mass spectrometry (MS). Antibodies isolated from young leaves have a
      relatively high amount of high- mannose glycans compared with antibodies from
      older leaves, which contain more terminal N-acetylglucosamine. Senescence was
      shown to affect the glycosylation profile of endogenous proteins. The relative
      amount of N-glycans without terminal N-acetylglucosamine increased with leaf age.
      Major differences were observed between glycan structures on endogenous proteins
      versus those on antibodies, probably to be attributed to their subcellular
      localization. The relatively high percentage of antibody N-glycan lacking both
      xylose and fucose is interesting.

PMID- 11457983
TI  - Role of nitric oxide synthase in the light-induced development of sporangiophores
      in Phycomyces blakesleeanus.
AB  - Blue light controls the development of sporangiophores in the zygomycete
      Phycomyces blakesleeanus Burgeff. Light represses the production of
      microsporangiophores and enhances the development of macrosporangiophores.
      Inhibition of the biosynthesis of tetrahydrobiopterin, a cofactor of NO synthase,
      inhibits this photomorphogenesis. Light induces production of citrulline from
      arginine in the mycelium and in sporangiophores. The citrulline-forming activity
      is dependent on NADPH, independent of calcium, and inhibited by NO synthase
      inhibitors. It is reduced in tetrahydrobiopterin-depleted mycelium. Light induces
      emission of NO from the developing fungus in the same order of magnitude as
      citrulline formation from arginine. The NO donor sodium nitroprusside can replace
      the light effect on sporangiophore development, and inhibitors of NO synthase
      repress it. We suggest that a fungal NO synthase is involved in sporangiophore
      development and propose its participation in light signaling.

PMID- 11457984
TI  - Sequence and analysis of the tomato JOINTLESS locus.
AB  - A 119-kb bacterial artificial chromosome from the JOINTLESS locus on the tomato
      (Lycopersicon esculentum) chromosome 11 contained 15 putative genes. Repetitive
      sequences in this region include one copia-like LTR retrotransposon, 13 simple
      sequence repeats, three copies of a novel type III foldback transposon, and four
      putative short DNA repeats. Database searches showed that the foldback transposon
      and the short DNA repeats seemed to be associated preferably with genes. The
      predicted tomato genes were compared with the complete Arabidopsis genome. Eleven
      out of 15 tomato open reading frames were found to be colinear with segments on
      five Arabidopsis bacterial artificial chromosome/P1-derived artificial chromosome
      clones. The synteny patterns, however, did not reveal duplicated segments in
      Arabidopsis, where over half of the genome is duplicated. Our analysis indicated
      that the microsynteny between the tomato and Arabidopsis genomes was still
      conserved at a very small scale but was complicated by the large number of gene
      families in the Arabidopsis genome.

PMID- 11457985
TI  - An overview of the determinants of CCR5 and CXCR4 co-receptor function.

PMID- 11457986
TI  - Distribution of ecotropic retrovirus receptor protein in rat brains detected by
      immunohistochemistry.
AB  - Friend murine leukaemia virus (FrMLV) FrC6 clone A8 causes spongiform
      degeneration in the central nervous system (CNS) of newborn but not 3-week-old
      rats. To assess whether expression of the ecotropic MLV receptor (CAT-1) in the
      CNS correlates with the pathogenicity of the A8 virus, we generated an anti-CAT-1
      antibody raised against a synthetic peptide that corresponds to the carboxyl
      terminal amino acid sequence of CAT-1. In the CNS of newborn and 3 to 4-week-old
      rats, a strong immunoreactivity against the antibody was detected in most of the
      endothelial cells. However, almost no expression of CAT-1 was detected in the CNS
      of 21-week-old rats. In newborn rats, many parenchymal cells in the brain as well
      as the vascular wall expressed CAT-1 antigen. These findings suggest that
      retrovirus receptor-bearing glial cells contribute to the neuropathogenesis of
      MLV, including clone A8, which induces spongiosis in rats only when inoculated
      into newborns.

PMID- 11457987
TI  - Gender-related differences in susceptibility, early virus dissemination and
      immunosuppression in mice infected with Friend murine leukaemia virus variant FIS
      2.
AB  - An emerging amount of data indicates a correlation between gender-related factors
      and regulation of virus infection and supports what is known in clinical circles,
      that these topics are of great importance in many infectious diseases. In the
      present study we found that young adult NMRI male mice are more susceptible to
      infection by a variant of Friend murine leukaemia virus, FIS-2, than are female
      mice. We observed that the level of virus in serum, bone marrow and spleen was
      initially higher in male mice. Male mice were also more susceptible to FIS-2
      induced immunosuppression. These results indicate a more efficient virus
      replication and dissemination in male mice. Studies with recombinant viruses
      between FIS-2 and the prototype Friend murine leukaemia virus revealed that FIS-2
      LTR is one major factor contributing to the observed gender differences. A
      possible sex hormone influence on FIS-2 transcription due to the presence of a
      glucocorticoid response element in FIS-2 LTR is discussed.

PMID- 11457988
TI  - Identification of a novel type C porcine endogenous retrovirus: evidence that
      copy number of endogenous retroviruses increases during host inbreeding.
AB  - Different classes of porcine endogenous retroviruses (PERVs), which have the
      potential to infect humans during xenotransplantation, have been isolated from
      the pig genome. Because vertebrate genomes may contain numerous endogenous
      retrovirus sequences, the pig genome was examined for additional endogenous
      retroviruses, resulting in the isolation of a novel, complete endogenous
      retrovirus genome, designated PERV-E. The gag, pol and env genes of PERV-E are
      closely related to those of human endogenous retrovirus (HERV) 4-1, which belongs
      to the HERV-E family. Results of studies to determine the presence and copy
      number of PERVs demonstrated that PERV-E and PERV-A/B-like proviruses were
      present in all genomes tested, but that PERV-C was not found in two of the
      species examined, including wild boar. Multiple copies of PERVs could be found in
      each pig genome. Among all of the pig genomes tested, the wild boar genome had
      the lowest copy number of all PERVs, suggesting that the number of integrations
      of complete endogenous retroviruses is increased by inbreeding.

PMID- 11457989
TI  - The haemagglutinin protein is an important determinant of measles virus tropism
      for dendritic cells in vitro.
AB  - Recombinant measles viruses (MV) in which the authentic glycoprotein genes
      encoding the fusion and the haemagglutinin (H) proteins of the Edmonston (ED)
      vaccine strains were swapped singly or doubly for the corresponding genes of a
      lymphotropic MV wild-type virus (strain WTF) were used previously to investigate
      MV tropism in cell lines in tissue culture. When these recombinants and their
      parental strains, the molecular ED-based clone (ED-tag) and WTF, were used to
      infect cotton rats, only viruses expressing the MV WTF H protein replicated in
      secondary lymphatic tissues and caused significant immunosuppression. In vitro,
      viruses containing the ED H protein revealed a tropism for human peripheral blood
      lymphocytes as documented by enhanced binding and virus production, whereas those
      containing the WTF H protein replicated well in monocyte-derived dendritic cells
      (Mo-DC). This did not correlate with more efficient binding of these viruses to
      DC, but with an enhancement of uptake, virus spread, accumulation of viral
      antigens and virus production. Thus, replacement of the ED H protein with WTF H
      protein was sufficient to confer the DC tropism of WTF to ED-tag in vitro. This
      study suggests that the MV H protein plays an important role in determining cell
      tropism to immune cells and this may play an important role in the induction of
      immunosuppression in vivo.

PMID- 11457990
TI  - Interaction between molecules of hantavirus nucleocapsid protein.
AB  - Intermolecular interactions of Tula hantavirus N (nucleocapsid) protein were
      detected in the yeast two-hybrid system, prompting further attempts to study this
      phenomenon. Using chemical cross-linking and immunoblotting it was shown that the
      N protein from purified virus and from infected cell lysates as well as
      recombinant protein produced in a baculovirus expression system are capable of
      forming dimers, trimers and multimers, thus confirming the capacity of the
      protein molecules to interact with each other. An ELISA format was developed in
      which molecules of the recombinant N protein were shown to associate non
      covalently, via electrostatic interactions. Divalent cations (Ca(2+), Mn(2+),
      Mg(2+), Ba(2+)) enhanced the process 3- to 8-fold suggesting that adequate
      folding of the N protein is crucial for the association. Based on these data a
      model for hantavirus nucleocapsid assembly is proposed, in which N molecules
      first trimerize around the viral RNA molecule, and then the trimers gradually
      assemble forming longer multimers.

PMID- 11457991
TI  - Comparisons among the larger genome segments of six nodaviruses and their encoded
      RNA replicases.
AB  - The Nodaviridae are a family of isometric RNA viruses that infect insects and
      fish. Their genomes, which are among the smallest known for animal viruses,
      consist of two co-encapsidated positive-sense RNA segments: RNA1 encodes the
      viral contribution to the RNA-dependent RNA polymerase (RdRp) which replicates
      the viral genome, whereas RNA2 encodes the capsid protein precursor. In this
      study, the RNA1 sequences of two insect nodaviruses - Nodamura virus (the
      prototype of the genus) and Boolarra virus - are reported as well as detailed
      comparisons of their encoded RdRps with those of three other nodaviruses of
      insects and one of fish. Although the 5' and 3' untranslated regions did not
      reveal common features of RNA sequence or secondary structure, these divergent
      viruses showed similar genome organizations and encoded RdRps that had from 26 to
      99% amino acid sequence identity. All six RdRp amino acid sequences contained
      canonical RNA polymerase motifs in their C-terminal halves and conserved elements
      of predicted secondary structure throughout. A search for structural homologues
      in the protein structure database identified the poliovirus RdRp, 3D(pol), as the
      best template for homology modelling of the RNA polymerase domain of Pariacoto
      virus and allowed the construction of a congruent three-dimensional model. These
      results extend our understanding of the relationships among the RNA1 segments of
      nodaviruses and the predicted structures of their encoded RdRps.

PMID- 11457992
TI  - Phylogenetic relationships of flaviviruses correlate with their epidemiology,
      disease association and biogeography.
AB  - Phylogenetic analysis of the Flavivirus genus, using either partial sequences of
      the non-structural 5 gene or the structural envelope gene, revealed an extensive
      series of clades defined by their epidemiology and disease associations. These
      phylogenies identified mosquito-borne, tick-borne and no-known-vector (NKV) virus
      clades, which could be further subdivided into clades defined by their principal
      vertebrate host. The mosquito-borne flaviviruses revealed two distinct
      epidemiological groups: (i) the neurotropic viruses, often associated with
      encephalitic disease in humans or livestock, correlated with the Culex species
      vector and bird reservoirs and (ii) the non-neurotropic viruses, associated with
      haemorrhagic disease in humans, correlated with the Aedes species vector and
      primate hosts. Thus, the tree topology describing the virus-host association may
      reflect differences in the feeding behaviour between Aedes and Culex mosquitoes.
      The tick-borne viruses also formed two distinct groups: one group associated with
      seabirds and the other, the tick-borne encephalitis complex viruses, associated
      primarily with rodents. The NKV flaviviruses formed three distinct groups: one
      group, which was closely related to the mosquito-borne viruses, associated with
      bats; a second group, which was more genetically distant, also associated with
      bats; and a third group associated with rodents. Each epidemiological group
      within the phylogenies revealed distinct geographical clusters in either the Old
      World or the New World, which for mosquito-borne viruses may reflect an Old World
      origin. The correlation between epidemiology, disease correlation and
      biogeography begins to define the complex evolutionary relationships between the
      virus, vector, vertebrate host and ecological niche.

PMID- 11457993
TI  - Functional analysis of hepatitis C virus E2 glycoproteins and virus-like
      particles reveals structural dissimilarities between different forms of E2.
AB  - Structure-function analysis of the hepatitis C virus (HCV) envelope
      glycoproteins, E1 and E2, has been difficult due to the unavailability of HCV
      virions. Truncated soluble forms of E2 have been used as models to study virus
      interaction with the putative HCV receptor CD81, but they may not fully mimic E2
      structures on the virion. Here, we compared the CD81-binding characteristics of
      truncated E2 (E2(660)) and full-length (FL) E1E2 complex expressed in mammalian
      cells, and of HCV virus-like particles (VLPs) generated in insect cells. All
      three glycoprotein forms interacted with human CD81 in an in vitro binding assay,
      allowing us to test a panel of well-characterized anti-E2 monoclonal antibodies
      (MAbs) for their ability to inhibit the glycoprotein-CD81 interaction. MAbs
      specific for E2 amino acid (aa) regions 396-407, 412-423 and 528-535 blocked
      binding to CD81 of all antigens tested. However, MAbs specific for regions 432
      443, 436-443 and 436-447 inhibited the interaction of VLPs, but not of E2(660) or
      the FL E1E2 complex with CD81, indicating the existence of structural differences
      amongst the E2 forms. These findings underscore the need to carefully select an
      appropriate ligand for structure-function analysis.

PMID- 11457994
TI  - Mapping of a dengue virus neutralizing epitope critical for the infectivity of
      all serotypes: insight into the neutralization mechanism.
AB  - Dengue virus infections are a growing public health concern and strategies to
      control the spread of the virus are urgently needed. The murine monoclonal
      antibody 4E11 might be of interest, since it neutralizes dengue viruses of all
      serotypes by binding to the 296-400 segment of the major dengue virus envelope
      glycoprotein (DE). When phage-displayed peptide libraries were screened by
      affinity for 4E11, phage clone C1 was selected with a 50% frequency. C1 shared
      three of nine residues with DE(306-314) and showed significant reactivity to 4E11
      in ELISA. C1-induced antibodies cross-reacted with DE(296-400) in mice,
      suggesting that it was a structural equivalent of the native epitope of 4E11 on
      DE. Accordingly, 4E11 bound to the DE(306-314) synthetic peptide and this
      reaction was inhibited by DE(296-400). Moreover, DE(306-314) could block dengue
      virus infection of target cells in an in vitro assay. A three-dimensional model
      of DE revealed that the three amino acids shared by DE(296-400) and C1 were
      exposed to the solvent and suggested that most of the amino acids comprising the
      4E11 epitope were located in the DE(306-314) region. Since 4E11 blocked the
      binding of DE(296-400) to heparin, which is a highly sulfated heparan sulfate
      (HSHS) molecule, 4E11 may act by neutralizing the interaction of DE(306-314) with
      target cell-displayed HSHS. Our data suggest that the DE(306-314) segment is
      critical for the infectivity of all dengue virus serotypes and that molecules
      that block the binding of DE(306-314) to HSHS may be antiviral reagents of
      therapeutic interest.

PMID- 11457995
TI  - Establishment of persistent infection with non-cytopathic bovine viral diarrhoea
      virus in cattle is associated with a failure to induce type I interferon.
AB  - The establishment of persistent infections with non-cytopathic bovine virus
      diarrhoea virus (ncpBVDV) is crucial for the maintenance of BVDV in cattle
      populations. Also, super-infection of persistently infected individuals with
      antigenically homologous cytopathic BVDV (cpBVDV) results in fatal mucosal
      disease. Persistent infection with ncpBVDV is established by infection of the
      foetus during the first trimester of pregnancy. It has been shown previously that
      foetal infection with cpBVDV does not result in persistent infection. Infection
      of cells in vitro has demonstrated that cpBVDV induces type I interferon (IFN),
      whereas ncpBVDV fails to induce IFN. In this study we demonstrate that foetal
      challenge with cpBVDV results in IFN production, whereas ncpBVDV does not. These
      findings strongly suggest that the ability of ncpBVDV to inhibit the induction of
      type I IFN has evolved to enable the virus to establish persistent infection in
      the early foetus.

PMID- 11457996
TI  - Human antibodies isolated from plasma by affinity chromatography increase the
      coxsackievirus B4-induced synthesis of interferon-alpha by human peripheral blood
      mononuclear cells in vitro.
AB  - Coxsackievirus B4 (CVB4) can be found in circulating blood of patients; however,
      the interaction of CVB4 with peripheral blood mononuclear cells (PBMCs) is poorly
      understood. CVB4 induced low levels of IFN-alpha synthesis in PBMCs from healthy
      donors. In contrast, preincubation of infectious CVB4 with plasma from these
      donors containing anti-CVB4 antibodies strongly enhanced the synthesis of IFN
      alpha. IgG obtained from plasma by chromatography formed immune complexes with
      CVB4 and increased significantly the CVB4-induced production of IFN-alpha by
      PBMCs. These antibodies did not have a neutralizing effect on CVB4 infection of
      Hep-2 cells. The role of CVB and adenovirus receptor (CAR), FcgammaRII and
      FcgammaRIII in the increased synthesis of IFN-alpha induced by CVB4 preincubated
      with IgG was shown by inhibition with specific antibodies. The major interferon
      alpha-producing cells in response to CVB4-IgG complexes were CD14(+) cells and
      monocyte-enriched PBMCs. With the latter, detection of IFN-alpha by
      immunostaining was positive whereas in monocyte-depleted PBMCs it was not. This
      study shows that CVB4-induced synthesis of IFN-alpha by PBMCs can be enhanced by
      an antibody-dependent mechanism through interactions between the virus, non
      neutralizing antivirus antibodies, FcgammaRII and III and CAR.

PMID- 11457997
TI  - Screening enteroviruses for beta-cell tropism using foetal porcine beta-cells.
AB  - Primary adult human insulin-producing beta-cells are susceptible to infection by
      prototype strains of coxsackieviruses (CV) and infection may result in impaired
      beta-cell function and/or cell death, as shown for coxsackie B virus (CVB) types
      4 and 5, or have no apparent immediate adverse effects, as shown for CVA-9.
      Because of the limited availability of human pancreatic beta-cells, the aim of
      this study was to find out if foetal porcine pancreatic islets could be used as a
      substitute in enterovirus (EV) screening. These cells resemble human beta-cells
      in several biological properties. CVB infection resulted in a rapid progressive
      decline of insulin content and reponsiveness to insulin release. The amount of
      virus inoculum sufficient for this destruction was small, corresponding to only
      55 infectious units per pancreas. In contrast to CVBs, CVA-9 replicated poorly,
      and sometimes not at all, in foetal porcine beta-cells. The first signs of
      functional impairment and cell destruction, if present at all, were seen only
      after 1-3 weeks of incubation. Furthermore, CVA-16, several strains of
      echoviruses and human parechovirus type 1 were unable to replicate in foetal
      porcine pancreatic beta-cells. Based on these results, foetal porcine islets are
      somewhat more sensitive to CVB infection than adult human islets, whereas many
      other human EV strains do not infect porcine beta-cells. Therefore, foetal
      porcine beta-cells cannot be used for systematic screening of human EV strains
      and isolates for beta-cell tropism, but they might provide a useful model for
      detailed studies on the interaction of CVBs with beta-cells.

PMID- 11457998
TI  - Role of conserved residues in the activity of adenovirus preterminal protein.
AB  - Preterminal protein (pTP) is a component of the preinitiation complex which forms
      at the adenovirus origin of DNA replication and acts as the protein primer during
      DNA synthesis. In order to determine the role of various regions of the molecule
      a series of 18 mutations was introduced into conserved motifs of pTP which were
      predicted to be surface exposed, and the mutants expressed in insect cells using
      a baculovirus expression system. Their ability to initiate DNA replication was
      assessed and the effect the mutations have on the individual interactions which
      contribute to the formation of the pre-initiation complex was determined. Classes
      of mutants could be identified which were unable to bind DNA or interact with the
      adenovirus DNA polymerase, but one class of mutants retained these activities and
      yet failed to initiate DNA replication. These mutants therefore identify regions
      of pTP required for different aspects of adenovirus DNA replication.

PMID- 11457999
TI  - Inhibition of transcription-regulating properties of nonstructural protein 1
      (NS1) of parvovirus minute virus of mice by a dominant-negative mutant form of
      NS1.
AB  - Nonstructural protein 1 (NS1) of minute virus of mice is involved in viral DNA
      replication, transcriptional regulation and cytotoxic action in the host cell.
      Viral DNA replication is dependent on the ability of NS1 to form homo-oligomers.
      To investigate whether oligomerization is required for NS1 transcriptional
      activities, a functionally impaired mutant derivative of NS1 that was able to
      interact with the wild-type (wt) protein and inhibit its activity in a dominant
      negative manner was designed. This mutant provided evidence that transactivation
      of the parvoviral P38 promoter and transinhibition of a heterologous promoter by
      NS1 were both affected by the co-expression of the wt and the dominant-negative
      mutant form of NS1. These results indicate that additional functions of NS1,
      involved in promoter regulation, require oligomer formation.

PMID- 11458000
TI  - Cys(9), Cys(104) and Cys(207) of simian virus 40 Vp1 are essential for infectious
      virion formation in CV-1 cells.
AB  - Structural studies have implicated Cys(9), Cys(104) and Cys(207) of simian virus
      40 (SV40) Vp1 in disulfide bond formation. Recently, we have shown the three
      cysteines to be essential for disulfide linkage of Vp1 complexes in vitro. Here,
      the role of the three cysteines was explored during the course of SV40 infection.
      Single-, double- and triple-mutant Vp1 at Cys(9), Cys(104) and Cys(207) continued
      to localize to the nuclei of transfected CV-1 cells and to bind DNA, but showed a
      range of abilities to form plaques. Only mutants containing the Cys(9)-->Ser
      change showed defects in plaque formation. Single mutants at Cys(9) formed small
      plaques; mutants at Cys(9). Cys(104), Cys(9). Cys(207) and Cys(9). Cys(104).
      Cys(207) formed no plaques. All three isolated revertants contained back
      mutations at the Vp1 Cys(9) codon. These results further confirm the involvement
      of the three Vp1 cysteines in protein-protein interactions during virus assembly.
      Cys(9) is critical for production of wild-type infectious virions, whereas
      Cys(104) and Cys(207) play secondary roles.

PMID- 11458001
TI  - Mutational analysis of the major heparan sulfate-binding domain of herpes simplex
      virus type 1 glycoprotein C.
AB  - Heparan sulfate (HS) has been identified as a receptor molecule for numerous
      microbial pathogens, including herpes simplex virus type 1 (HSV-1). To further
      define the major HS-binding domain of the HSV-1 attachment protein, i.e.
      glycoprotein C (gC), virus mutants carrying alterations of either two
      neighbouring basic amino acid residues or a single hydrophobic amino acid residue
      within the N-terminal domain of the protein (residues 26-227) were constructed.
      In addition, a mutant lacking the Asn148 glycosylation site was included in the
      study. Binding of purified mutated gC proteins to isolated HS chains showed that
      viruses with mutations at residues Arg(129,130), Ile142, Arg(143,145),
      Arg(145,147), Arg(151,155) and Arg(155,160) had significantly impaired HS
      binding, in contrast to the other mutations, including Asn148. Impairment of the
      HS-binding activity of gC by these mutations had profound consequences for virus
      attachment and infection of cells in which amounts of HS exposed on the cell
      surface had been reduced. It is suggested that basic and hydrophobic residues
      localized at the Cys127-Cys144 loop of HSV-1 gC constitute a major HS-binding
      domain, with the most active amino acids situated near the C-terminal region of
      the two cysteines.

PMID- 11458002
TI  - Mitogen stimulation favours replication of equine herpesvirus-1 in equine blood
      mononuclear cells by inducing cell proliferation and formation of close
      intercellular contacts.
AB  - In the present study, equine herpesvirus-1 (EHV-1)-infected cells were identified
      in ionomycin/phorbol dibutyrate (IONO/PDB)-stimulated peripheral blood
      mononuclear cells (PBMC) and the mechanism by which stimulation increases the
      percentage of infected cells was examined. In the population of viral antigen
      positive PBMC, 38.4+/-4.5% were CD5(+) T-lymphocytes (18.1+/-3.2% CD4(+) 13.6+/
      1.8% CD8(+)), 18.1+/-5.4% were B-lymphocytes, 8.5+/-3.9% were monocytes and 35%
      remained unidentified. The role of the cell cycle in the increased susceptibility
      to EHV-1 upon stimulation was examined by stimulating PBMC for 0, 12, 24 or 36 h
      prior to inoculation. A high correlation was found between the increase of cells
      in the S- (r=0.974) and G(2)/M-phase (r=0.927) at the moment of inoculation and
      the increase of infected cells at 12 h post-inoculation (p.i.). This suggests
      that a specific stage of the S-phase or S- and G(2)/M-phase facilitates virus
      replication. At 24 h p.i. lower correlations were found, suggesting that other
      effects are involved. From 12 h after addition of IONO/PDB, formation of clusters
      of PBMC became manifest. We examined whether close intercellular contacts in
      these clusters facilitated cell-to-cell transmission of EHV-1. Between 8 and 17 h
      p.i., the percentage of clusters containing adjacent infected cells increased
      from 1.6 to 13.4% and the maximal number of adjacent infected cells increased
      from two to four. Confocal microscopy visualized close intercellular contacts
      between adjacent infected cells. It can be concluded that mitogen stimulation
      favours EHV-1 infection of PBMC (i) by initiating specific cell cycle events and
      (ii) by inducing formation of clusters, thereby facilitating transmission of
      virus between cells.

PMID- 11458003
TI  - Multimeric humanized varicella-zoster virus antibody fragments to gH neutralize
      virus while monomeric fragments do not.
AB  - Murine monoclonal antibody 206 (MAb mu206) binds to gH, the varicella-zoster
      virus (VZV) fusogen, neutralizing the virus in vitro in the absence of complement
      and inhibiting cell-to-cell spread and egress of VZV in cultured cells. We have
      humanized this antibody to generate MAb hu206 by complementarity determining
      region grafting. MAb hu206 retained binding and in vitro neutralizing activity,
      as well as cross-reactivity with ten different VZV strains. Single-chain antibody
      fragments (scAb) derived from MAb hu206 were produced in Escherichia coli. These
      scAb retained the binding properties of the whole antibody. However, monomeric
      scAb exhibited markedly reduced neutralizing activity compared to the bivalent
      parental MAb hu206. Shortening the peptide linker joining the V(H) to the
      V(kappa) domain from 14 to 5 or even 0 residues encouraged multimerization and
      increased neutralizing efficacy. The fact that Fab fragments enzymatically
      generated from whole MAb hu206 lost their neutralizing potency lent support to
      the proposal that valency is important for VZV neutralization at this epitope.

PMID- 11458004
TI  - Human herpesvirus-8 (Kaposi's sarcoma-associated herpesvirus) ORF50 interacts
      synergistically with the tat gene product in transactivating the human
      immunodeficiency virus type 1 LTR.
AB  - Human herpesvirus-8 (HHV-8) is a lymphotropic virus associated with several AIDS
      related neoplasms. Two ORFs play a critical role in the regulation of virus
      replication: ORF50, encoding an immediate-early transcriptional activator, and
      ORF57, encoding a post-transcriptional regulator. We analysed their effects on
      the activation of the human immunodeficiency virus type 1 (HIV-1) LTR. ORF50
      interacted synergically with tat, inducing a 10-fold enhancement of HIV-1 LTR
      transactivation. This effect occurred both in BCBL-1 cells, latently infected
      with HHV-8, and in HL3T1 cells, an epithelial cell line non-permissive to HHV-8
      infection. Also, ORF57 enhanced tat-induced transactivation of HIV-1 LTR, but
      only in BCBL-1 cells, suggesting that its action was likely mediated by the
      induction of other viral functions. Finally, when both ORFs were expressed, the
      enhancement of transactivation induced by ORF50 was partially inhibited. The
      findings suggest that ORF57 can modulate ORF50 activity and that ORF50 may render
      biologically active small amounts of tat.

PMID- 11458005
TI  - Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and
      morbidity.
AB  - The immune system uses both virus-specific T cells and B cells to control the
      acute and latent phases of respiratory infection with the murine gammaherpesvirus
      68 (gammaHV-68). We sought to further define the important effector mechanisms
      for CD8(+) T cells. First, depletion of the CD4(+) T cells resulted in a failure
      of most animals to drive the virus into latency, although lytic virus in the lung
      was reduced by approximately 1000-fold from its peak. Second, the absence of
      either perforin or Fas alone had no impact on the ability to reduce titres of
      lytic virus in the lung. Further neutralization of IFN-gamma in CD4-depleted
      P(+/+), P(-/-) or Fas(-/-) mice had no effect. To define the requirements for Fas
      or perforin more clearly, two sets of chimeric mice were constructed differing in
      perforin expression by the T cells, and Fas on infected epithelial cells or
      lymphocytes. Animals with P(-/-) T cells and a Fas(-/-) lung failed to limit the
      shedding of infectious virus, regardless of whether CD4 T cells were present. In
      addition, we noted that having P(-/-) T cells in irradiated Fas(+/+) hosts caused
      a lethal disease that was not apparent in the non-chimeric (unirradiated) P(-/-)
      (Fas(+/+)) mice. In another set of chimeric mice, P(-/-) T cells were able to
      limit persistent infection of B cells that expressed Fas, but not B cells that
      were Fas-deficient. These studies demonstrate that some degree of cytotoxicity
      via either perforin or Fas is essential for CD8(+) T cells to control this DNA
      virus.

PMID- 11458006
TI  - Ultrastructural localization and epitope mapping of the methyltransferase-like
      and helicase-like proteins of Beet yellows virus.
AB  - Monoclonal antibodies (MAbs) specific to the methyltransferase (MT) and helicase
      (HEL) domains of the closterovirus Beet yellows virus (BYV) were used for
      immunogold labelling of ultrathin sections of virus-infected Tetragonia expansa
      plants. MAbs 4A2 and 4A5 from the MT panel, and 1C4 from the HEL panel,
      specifically labelled distinct closterovirus-induced membranous structures, the
      'BYV-type vesicles', thus suggesting that the closterovirus MT-like and HEL-like
      proteins co-localize in these structures. Probing of the MT and HEL MAbs with
      synthetic octapeptides spanning the sequences of the recombinant MT and HEL
      fragments that had been used as immunogens showed that 4A5 and 4A2 recognized a
      single epitope, SRLLENET (aa 686-692 in the BYV 1a protein), and 1C4 reacted with
      the DDPF epitope (aa 2493-2496). These epitopes apparently reside on the exposed
      parts of the membrane-associated molecules of the closterovirus MT-like and HEL
      like proteins. Two other epitopes determined for the MT MAbs that were
      nonreactive in the immunogold labelling, namely TMVTPGEL (aa 750-757; MAbs 3C5,
      4B4 and 4C5) and SREQLVEA (aa 806-813; MAb 2A4), are possibly buried in the MT
      domain fold or shielded by membranes or other proteins involved in the viral
      replicative complex.

PMID- 11458007
TI  - Studies on the role of the minor capsid protein in transport of Beet western
      yellows virus through Myzus persicae.
AB  - Beet western yellows virus (BWYV), family Luteoviridae, is an icosahedral plant
      virus which is strictly transmitted by aphids in a persistent and circulative
      manner. Virions cross two cellular barriers in the aphid by receptor-based
      mechanisms involving endocytosis and exocytosis. Particles are first transported
      across intestinal cells into the haemolymph and then across accessory salivary
      gland cells for delivery to the plant via saliva. We identified the midgut part
      of the digestive tract as the site of intestinal passage by BWYV virions. To
      analyse the role in transmission of the minor capsid component, the readthrough
      (RT) protein, the fate of a BWYV RT-deficient non-transmissible mutant was
      followed by transmission electron microscopy in the vector Myzus persicae. This
      mutant was observed in the gut lumen but was never found inside midgut cells.
      However, virion aggregates were detected in the basal lamina of midgut cells when
      BWYV antiserum was microinjected into the haemolymph. The presence of virions in
      the haemolymph was confirmed by a sensitive molecular technique for detecting
      viral RNA. Thus, transport of the mutant virions through intestinal cells
      occurred but at a low frequency. Even when microinjected into the haemolymph, the
      RT protein mutant was never detected near or in the accessory salivary gland
      cells. We conclude that the RT protein is not strictly required for the transport
      of virus particles through midgut cells, but is necessary for the maintenance of
      virions in the haemolymph and their passage through accessory salivary gland
      cells.

PMID- 11458008
TI  - Complete nucleotide sequence and genome organization of Grapevine fleck virus.
AB  - The complete nucleotide sequence of Grapevine fleck virus (GFkV) genomic RNA was
      determined. The genome is 7564 nt in size, excluding the 3'-terminal poly(A)
      tail, is characterized by an extremely high cytosine content (ca. 50%), and
      contains four putative open reading frames and untranslated regions of 291 and 35
      nt at the 5' and 3' ends, respectively. ORF 1 potentially encodes a 215.4 kDa
      polypeptide (p215), which has the conserved motifs of replication-associated
      proteins of positive-strand RNA viruses. ORF 2 encodes a 24.3 kDa polypeptide
      (p24) identified as the coat protein. ORFs 3 and 4 are located at the extreme 3'
      end of the viral genome and encode proline-rich proteins of 31.4 kDa (p31) and
      15.9 kDa (p16), respectively, of unknown function. Phylogenetic analysis of the
      viral replicase and coat protein genes showed that GFkV is related to members of
      the Tymovirus and Marafivirus genera. Two subgenomic RNAs were present in the
      GFkV preparations as ascertained by molecular hybridization. The genome
      organization of GFkV resembles to some extent that of tymoviruses and
      marafiviruses. However, differences in the biological and epidemiological
      behaviour, cytopathology and molecular properties (i.e. size of genomic RNA and
      coat protein, and number of ORFs) support the notion that GFkV is a separate
      virus belonging in a new genus.

PMID- 11458010
TI  - Introduction.

PMID- 11458009
TI  - Cellular prion protein status in sheep: tissue-specific biochemical signatures.
AB  - Expression of the cellular prion protein PrP(C) is sine qua none for the
      development of transmissible spongiform encephalopathy and thus for the
      accumulation of the illness-associated conformer PrP(Sc). Therefore, the tissue
      distribution of PrP(C) at the protein level in both quantitative and qualitative
      terms was investigated. PrP(C) was quantified using a two-site enzyme
      immunometric assay which was calibrated with purified ovine recombinant prion
      protein (rPrP). The most PrP(C)-rich tissue was the brain, followed by the lungs,
      skeletal muscle, heart, uterus, thymus and tongue, which contained between 20-
      and 50-fold less PrP(C) than the brain. The PrP(C) content of these tissues seems
      to be comparable between sheep. Other organs, however, showed different, but low,
      levels of the protein depending on the animal examined. This was also the case
      for tissues from the gastrointestinal tract. The tissue containing the lowest
      concentration of PrP(C) was shown to be the liver, where PrP(C) was found to be
      between 564- and 16000-fold less abundant than in the brain. PrP(C) was
      concentrated from crude cellular extracts by immunoprecipitation using several
      monoclonal and polyclonal anti-ovine PrP antibodies. Interestingly, it was
      observed that the isoform profile of PrP(C) was tissue-specific. The most
      atypical electrophoretic profile of PrP(C) was found in the skeletal muscle,
      where two polypeptides of 32 and 35 kDa were detected.

PMID- 11458012
TI  - Expanding applications to peripheral interventions.

PMID- 11458011
TI  - Low-molecular-weight heparins.

PMID- 11458013
TI  - Facilitated PCI: rationale and design of the FINESSE trial.

PMID- 11458014
TI  - Combination therapy with reduced-dose fibrinolytic and platelet GP IIb/IIIa
      receptor inhibitors: SPEEDing into GUSTO V.

PMID- 11458015
TI  - Fibrinolytic monotherapy for acute myocardial infarction.

PMID- 11458017
TI  - Preoperative oral carbohydrate nutrition: an update.
AB  - Insulin resistance is a central feature of the metabolic response after elective
      surgery as well as other trauma, and has been shown to be a predictor of the
      length of stay after surgery. Carbohydrate treatment instead of overnight fasting
      before surgery has been shown to reduce postoperative insulin resistance and to
      reduce hospital stay approximately 20% after elective surgery. For potential use
      as a clinical routine before surgery, a carbohydrate-rich drink was developed.
      Gastric emptying of a 50 g oral carbohydrate load using this drink is complete
      within 90 min after intake. Oral carbohydrate loading before surgery has
      confirmed previous data, using glucose and insulin infusions, that postoperative
      insulin resistance is reduced compared with overnight fasted patients before
      surgery, and this is associated with improved well-being before and after
      surgery.

PMID- 11458018
TI  - Non-invasive studies of glycogen metabolism in human skeletal muscle using
      nuclear magnetic resonance spectroscopy.
AB  - Nuclear magnetic resonance spectroscopy provides non-invasive and real-time
      assessment of the metabolic fluxes in skeletal muscle during exercise, recovery
      from exercise and stimulation by insulin. Carbon-13 nuclear magnetic resonance
      spectroscopy has proved that reduced glycogen synthesis is a consistent feature
      of insulin-resistant type 2 diabetic patients, their offspring, and obesity. Low
      intracellular glucose and glucose-6-phosphate concentrations indicate that
      decreased glucose transport is mainly responsible for common insulin resistance.
      An elevation of plasma free fatty acids causes similar alterations of muscle
      glucose metabolism, and could play a central role in the development of impaired
      muscle glucose transport associated with insulin resistance.

PMID- 11458019
TI  - New data and concepts on glutamine and glucose metabolism in the gut.
AB  - Both glutamine and glucose are highly utilized by the small intestine in various
      animal species. They are, however, very partially oxidized, the major known fate
      of glucose being lactate and alanine, and that of glutamine being citrulline or
      proline. At variance with the current view that only the liver and kidney are
      gluconeogenic organs, because both are the only tissues to express the glucose-6
      phosphatase gene, this gene is also expressed in the small intestine in rats and
      humans, and is strongly induced in insulinopenic states, such as fasting and
      diabetes. Under the latter conditions, the small intestine contributes 20-25% of
      whole-body endogenous glucose production. The main small intestine gluconeogenic
      substrate is glutamine and, to a lesser extent, glycerol. Accounting for these
      fluxes, the phosphoenolpyruvate carboxykinase gene is strongly induced in
      insulinopenia and, although up to now it had been considered absent from this
      tissue, the glycerokinase gene is expressed in the small intestine. The
      production of glucose by the small intestine may be acutely blunted upon insulin
      infusion. These new data also emphasize the central role of alanine
      aminotransferase in the coupling of glutamine and glucose metabolisms in the
      small intestine.

PMID- 11458020
TI  - New data and new concepts on the role of the liver in glucose homeostasis.
AB  - The liver plays a central role in the control of glucose production. It is also
      involved in the regulation of insulin secretion and sensitivity through neural
      pathways. This review will address recent developments in the mechanisms by which
      hepatic metabolism affects glucose homeostasis in health and disease. Oral
      glucose feeding elicits several systemic and hepatic alterations of intermediary
      metabolism through the activation of neural pathways. How this may affect glucose
      metabolism will be briefly discussed, and alterations of glucose homeostasis in
      liver disease will be briefly described. There is evidence that a portion of
      intrahepatic glucose can be converted into lipids in the process of de-novo
      lipogenesis. How this may be involved in the control of glycaemia and lipid
      concentrations will be reviewed. Finally, molecular mechanisms by which the
      alteration of liver metabolism may affect systemic glucose homeostasis will be
      outlined.

PMID- 11458021
TI  - Inter-relationships between renal metabolism (both in physiology and renal
      dysfunction) and the liver.
AB  - Recently, evaluation of organ-specific glucose release showed that renal glucose
      release is of the same order of magnitude as splanchnic glucose release during
      the postabsorptive period. Moreover, renal glucose release appeared to be more
      sensitive to hormone action than did hepatic glucose release, and appeared to
      have a pre-eminent role during the adaptation to various physiological and
      pathological conditions. The kidney is now recognized as playing a key role in
      interorgan glucose metabolism, and particularly in the Cori cycle and glutamine
      glucose cycle. During chronic renal failure the suppression of renal glucose
      release, together with impaired hormone action, decreased glycogen storage and
      abnormal liver gluconeogenesis, are responsible for an increased risk for
      hypoglycaemia.

PMID- 11458022
TI  - Glucose and the ischemic brain: a sour grape or a sweet treat?
AB  - The lactic acidosis hypothesis of cerebral ischemia has relied on a single
      finding to support its main postulate: pre-ischemic hyperglycemia-aggravated
      ischemic brain damage. Although this finding is by no means the proof that the
      lactic acidosis hypothesis desperately needs, the premise of the hypothesis has
      been employed in hospitals around the world. A better understanding of some of
      the processes involved in elevating blood glucose levels pre-ischemia and their
      influence on the ischemic brain is now available. This understanding offers a
      unique opportunity to re-examine old dogmas and propose new ideas, in the form of
      an alternative hypothesis to explain 'the glucose paradox of cerebral ischemia'.

PMID- 11458023
TI  - Nutritional status and the elderly: the challenge ahead.

PMID- 11458024
TI  - Ageing and muscle: the effects of malnutrition, re-nutrition, and physical
      exercise.
AB  - Because of the metabolic changes caused by ageing, malnutrition is accompanied by
      a preferential loss of fat-free mass in the elderly, and it exaggerates the
      physiological loss of body cell mass, muscle mass and muscle function observed in
      the aged. Exercise training has positive anabolic effects even in the frail
      elderly, and may improve the effect of re-nutrition in malnourished elderly
      patients.

PMID- 11458025
TI  - Weightlessness as an accelerated model of nutritional disturbances.
AB  - Food intake and eating patterns, body functions and composition are significantly
      altered by short-duration space flight. Prolonged missions lasting weeks or
      months further aggravate these changes, and are responsible for acute or chronic
      physical impairments at return to ground conditions. Current projects of missions
      to Mars, resulting in 2 years of microgravity conditions, stress the critical
      need for the development of optimal nutritional programs and physical
      countermeasures to prevent body mass and function alterations. This review
      outlines ground models of microgravity simulation, summarizes the major effects
      of weightlessness on body composition, protein metabolism, hormonal pattern, and
      muscle function, and addresses contradictory findings related to the oxidative
      stress secondary to space flight. Potential countermeasures, such as nutrient
      intake and physical conditioning, as well as areas of interest for future
      research both in ground and space medicine, are discussed.

PMID- 11458026
TI  - Energy and fluid metabolism in microgravity.
AB  - Astronauts lose body mass when exploring space. The mechanism was considered to
      be an upward fluid shift inducing diuresis and natriuresis (the Henry-Gauer
      mechanism) during the first few days in microgravity. However, recent space
      missions have shown that neither diuresis nor natriuresis occurs in space
      missions. In contrast, a sodium-retaining status was shown, which led to positive
      metabolic sodium balances without fluid retention. Energy intake was consistently
      reduced whereas energy needs were unchanged, resulting in a negative energy
      balance of 20%. The reasons for this are many, although proper studies on
      appetite regulation have not been carried out. Despite numerous countermeasures,
      bone mass is lost in microgravity situations. These are body composition changes
      that need to be challenged before humans can be sent to space for extra-long
      missions.

PMID- 11458027
TI  - Management of catabolism in metabolically stressed patients: a literature survey
      about growth hormone application.
AB  - In the effort to improve the long-term outcome in critically ill patients, the
      utilization of anabolic agents, such as human recombinant growth hormone, has
      been proposed in order to reduce catabolism and improve nutritional status. A
      recent multicentre study regarding the use of human recombinant growth hormone in
      intensive care unit patients showed an unexpected increase in the mortality rate
      in human recombinant growth hormone-treated patients. This finding is in contrast
      with previous literature data reporting either no differences or an even lower
      mortality rate with the administration of human recombinant growth hormone. This
      review evaluates the possible reasons for this dramatic difference in outcomes
      between the multicentre study and the existing literature. Articles dealing with
      human recombinant growth hormone administration either in intensive care unit
      patients (n=26) or in postoperative patients (n=16) have been reviewed. Our
      analysis suggests that the low caloric intake given to patients enrolled in the
      multicentre study might have been inadequate to compensate for the
      hypermetabolism of these patients, and could not support the prolonged and
      delayed administration of high doses of human recombinant growth hormone. Whether
      the beneficial metabolic effects of human recombinant growth hormone translate
      into better clinical outcomes deserves further investigation. In addition, the
      careful selection of patients to be treated, and close monitoring of both the
      adequacy of caloric support and modality of human recombinant growth hormone
      administration would favour the safety of human recombinant growth hormone
      utilization in critical care settings.

PMID- 11458029
TI  - Genetic manipulation of the renin-angiotensin system.
AB  - The renin-angiotensin system is widely known for its importance in control of
      blood pressure, electrolyte homeostasis and volume regulation. Recently, renin
      angiotensin system function was studied using homologous recombination in
      embryonic stem cells to manipulate the mouse genome. Angiotensinogen, angiotensin
      converting enzyme and angiotensin II receptors were each eliminated in separate
      lines of mice. These null animals share similar phenotypes, such as a lowering of
      blood pressure, abnormal renal development, malfunction of the kidney and,
      unexpectedly, a decrease in hematocrit. In addition, angiotensin-converting
      enzyme null male mice sire far smaller litters than male wild-type mice. This
      suggests an unexplored role for angiotensin-converting enzyme in conception.
      Future studies with these and other genetically engineered mice lines will reveal
      novel physiological effects of angiotensin II.

PMID- 11458030
TI  - Genetic forms of human hypertension.
AB  - Our basic understanding of sodium mechanisms provides unique insights into
      epithelial transport processes, and unusual clinical syndromes can arise from
      mutations of these ion transporters. These genetic disorders affect sodium
      balance, with both sodium-retaining and sodium-wasting conditions being the
      consequence. A major focus of such studies has been the epithelial sodium
      channel, which can be activated by mutations in the channel subunits or
      mineralocorticoid receptor, and changes in the response to or production of
      mineralocorticoids. As a result, there are now clearly defined Mendelian
      syndromes in which epithelial sodium channel activity is 'dysregulated', with the
      subsequent development of systemic hypertension with suppressed plasma renin
      activity that can be attributed to a primary renal mechanism. Applying these
      insights to the far more common disorder of low renin hypertension may shed new
      light on the underlying pathophysiology of this common form of human
      hypertension, and more clearly define the interactions of dietary constituents
      such as sodium and potassium in the regulation of blood pressure.

PMID- 11458031
TI  - Hypertension trials: 1990 to 2000.
AB  - A large number of randomized controlled trials have been published over the past
      decade. The earlier ones established the benefits of low-dose diuretic-based
      therapy. The more recent ones have documented the equal overall effectiveness of
      therapy based on an angiotensin-converting enzyme inhibitor or a calcium
      antagonist. The comparative data do not clearly define a single superior drug for
      most hypertensive patients, so the initial choice should be individualized, on
      the basis of the concomitant conditions. For the rapidly increasing population of
      diabetic hypertensive patients, similar conclusions are obvious, with the caveat
      that an angiotensin-converting enzyme inhibitor should usually be the initial
      choice, with diuretics and calcium antagonists usually needed to accomplish
      adequate control. There are no concerns about the use of calcium antagonists in
      diabetic patients.

PMID- 11458032
TI  - Selective aspects of the insulin resistance syndrome.
AB  - There is increasing recognition of new features in the insulin resistance
      syndrome and its association with new disease states or treatment modalities.
      Recent additions to the list of features in the insulin resistance syndrome
      include elevated non-esterified fatty acids, abnormalities in visceral fat
      metabolism, elevated uric acid, elevated hematocrit, endothelial dysfunction,
      abnormalities in glucocorticoids, and differences in the phenotypic expression of
      the syndrome between men and women. A critical factor that may be inherent in the
      syndrome is the distribution and metabolism of visceral fat. This finding is also
      accompanied by the recognition of the role of non-esterified fatty acids as a
      cause of many of the risk factors in the insulin resistance syndrome. Elevated
      non-esterified fatty acids contribute to hypertension, glucose intolerance and
      increased arteriosclerosis. Elevated cortisol levels and disrupted metabolism, as
      well as abnormalities in the hypothalamic-pituitary-adrenal axis are seen in the
      insulin resistance syndrome. In women, adipose cells express fewer glucocorticoid
      receptors and less of the enzyme that metabolizes cortisol, 11beta-hydroxysteroid
      dehydrogenase. Several inflammatory factors such as tumor necrosis factor-alpha
      may be an etiologic link in the risk found in the insulin resistance syndrome.
      Certain cases of the syndrome appear to be related to specific drug therapies
      (steroids, immunosuppressive agents and antiretroviral agents), as seen in
      transplant patients and HIV-infected individuals.

PMID- 11458033
TI  - Evolving strategies for renoprotection: diabetic nephropathy.
AB  - A cumulative incidence of diabetic nephropathy of 25-40% has been documented
      after duration of diabetes of at least 25 years in both type 1 and type 2
      diabetic patients. Diabetic nephropathy has become the leading cause (25-44%) of
      end-stage renal failure in Europe, the United States and Japan. Until the early
      1980s, no renoprotective treatment was available for use in diabetic nephropathy.
      Death occurred on average 5-7 years after the onset of persistent proteinuria. It
      should be recalled that development of treatment modalities occurred in reverse
      order: in the early 1980s, antihypertensive treatment of diabetic nephropathy was
      introduced, and in the early 1990s, primary and secondary prevention with
      improved glycaemic control and angiotensin-converting enzyme inhibition. The two
      main treatment strategies for primary prevention of diabetic nephropathy are
      improved glycaemic control and blood pressure lowering, particularly using drugs
      such as angiotensin-converting enzyme inhibitors. Megatrials and meta-analyses
      have clearly demonstrated the beneficial effect of both the above-mentioned
      treatment modalities. Secondary prevention, that is, treatment modalities applied
      to diabetic patients with high risk of development of diabetic nephropathy (e.g.
      those with microalbuminuria) has been documented, applying angiotensin-converting
      enzyme inhibitors in both type 1 and type 2 diabetic patients. Furthermore,
      improved metabolic control reduces the risk of progression. In special cases
      (such as pancreas transplantation) even reversal of diabetic glomerular lesions
      has been documented. Antihypertensive treatment of patients with overt
      nephropathy induces a reduction in albuminuria, a reduction in the rate of
      decline of glomerular filtration rate, delays development of end-stage renal
      failure and improves survival. Many potential treatment modalities in preventing
      and treating diabetic nephropathy are presently being evaluated.

PMID- 11458034
TI  - Evolving strategies for renoprotection: non-diabetic chronic renal disease.
AB  - Experimental and clinical studies over the past two decades have identified
      several interventions for slowing the progression of chronic renal disease
      towards end-stage renal failure. In this paper we review the experimental and
      clinical evidence in support of dietary protein restriction, angiotensin
      converting enzyme inhibitor therapy, control of systemic hypertension, reduction
      of proteinuria, treatment of hyperlipidemia and smoking cessation. We also
      consider potential future renoprotective therapies. Finally we propose a
      comprehensive strategy for achieving maximal renoprotection with available
      interventions and monitoring.

PMID- 11458035
TI  - Polycystic kidney disease: from the bedside to the gene and back.
AB  - Collated in this highly personal commentary are the most important research
      findings of the past 10 years that deal primarily with the renal manifestations
      of inherited polycystic kidney diseases. Progress in understanding these complex
      disorders has followed two major concurrent and convergent lines of
      investigation: genes and genetic mechanisms, and pathogenesis and progression.
      The field has moved from descriptive pathobiology to the elucidation of molecular
      mechanisms consequent to genetic and epigenetic events. Doubtless, the favorite
      works of some who have labored diligently in this field have not been fully
      exalted, and for this I apologize. Were I the editor, this entire celebratory
      volume would be used to extol the thrilling growth of knowledge during the tenure
      of this polycystic kidney disease watcher.

PMID- 11458036
TI  - Molecular basis of glomerular permselectivity.
AB  - Recent discoveries in kidney research have given new insights into the molecular
      make-up of the glomerular filter and mechanisms of permselectivity. The
      identification of mutations in the genes for glomerular basement membrane type IV
      collagen has thus demonstrated the central role of the glomerular basement
      membrane as the structural skeleton of the glomerular capillary. Regional
      deterioration of this framework not only leads to proteinuria, but also to
      significant leakage of red blood cells into the urinary space. Tracer studies and
      the characterization of other glomerular basement membrane components, such as
      proteoglycans, have also emphasized the role of the glomerular basement membrane
      in the permselectivity process. However, more recent studies on nephrin, a key
      component of the slit diaphragm, as well as the podocyte and slit diaphragm
      associated intracellular proteins, CD2-associated protein, podocin and alpha
      actinin-4, have emphasized the role of the slit diaphragm as a central size
      selective filtration barrier. These data have provided a completely new
      understanding of the mechanisms of proteinuria, both in inherited and acquired
      diseases. In this review, we present the recent progress made in the
      characterization of proteins that are important for glomerular permselectivity.

PMID- 11458037
TI  - The pathological interpretation and significance of prostate needle biopsy
      findings: implications and current controversies.
AB  - PURPOSE: The widespread use of prostate specific antigen testing and digital
      rectal examination has lead to the increasing application of prostate needle
      biopsy. A larger proportion of men undergoing biopsy have small foci of cancer,
      which coupled with the overall increase in needle biopsy has led to a surge in
      the number of equivocal biopsy specimens interpreted. MATERIALS AND METHODS: We
      reviewed the literature with an overview of the topic of prostate needle biopsy
      pathology results with an emphasis on current controversies. RESULTS: The
      diagnosis rendered on prostate needle biopsy pay be placed into 4 major
      categories, including 1) benign, 2) prostatic intraepithelial neoplasia, 3)
      atypical and suspicious for cancer, and 4) prostate cancer. Prostatic
      intraepithelial neoplasia or a diagnosis of atypical and suspicious for cancer
      mandates re-biopsy in a search for occult prostate cancer. Biopsy findings,
      including the location of positive cores, may help to guide re-biopsy strategies.
      Prostate cancer on needle biopsy may be evaluated by numerous techniques of
      quantifying tumor extent, Gleason score and perineural invasion. These modalities
      may help clinicians to assess the risk of extraprostatic disease and progression
      likelihood, and help men with prostate cancer choose among therapeutic options.
      CONCLUSIONS: The pathology reports returned on needle biopsy specimens may
      provide a wealth of information beyond the simple presence or absence of prostate
      cancer that may aid clinicians in patient treatment and counseling.

PMID- 11458038
TI  - Fixed and dynamic urethral compression for the treatment of post-prostatectomy
      urinary incontinence: is history repeating itself?
AB  - PURPOSE: We reviewed the evolution of appliances and devices used for treating
      post-prostatectomy urinary incontinence. MATERIALS AND METHODS: We used the
      MEDLINE to search the literature from 1966 to March 2000 and then manually
      searched bibliographies to identify studies that our initial search may have
      missed. RESULTS: The evolution of treatment for post-prostatectomy urinary
      incontinence may be traced back to the 18th century. Two main schools of thoughts
      simultaneously evolved. The first fixed urethral compression devices were
      constructed to enable urethral obstruction by fixed resistance. This outlet
      resistance allows voiding after intra-abdominal and intravesical pressure is
      elevated but it is sufficient to prevent leakage between urinations. The other
      school of thought preferred creation of dynamic urethral compression in which
      outlet resistance is not fixed but may be decreased when voiding is desired or
      elevated between urinations. Therapeutic fixed and dynamic urethral compression
      interventions may be further divided into external or internal compressive
      devices or procedures. External fixed compression devices may be traced back to
      antiquity. A penile clamp, similar to the later Cunningham clamp, and a truss
      designed to compress the urethra by external perineal compression were presented
      in the Heister textbook of surgery, Institutiones Chirurgicae, as early as 1750.
      Dynamic compressive devices applied externally were developed much later, such as
      the first artificial urinary sphincter, described by Foley, in 1947 and the
      Vincent apparatus, described in 1960. The modern era of fixed urethral
      compression began in 1961 with Berry. Acrylic prostheses impregnated with bismuth
      to allow radiographic visualization were produced in various shapes and sizes,
      and used to compress the urethra against the urogenital diaphragm. In 1968 the
      University of California-Los Angeles group under the direction of Kaufman began
      to use cavernous crural crossover to compress the bulbous urethra (Kaufman I).
      Later 2 other modifications were described, including approximation of the crura
      in the midline using a polytetrafluoroethylene mesh tape (Kaufman II) and an
      implantable silicone gel prosthesis (Kaufman III). With the advent of the
      artificial urinary sphincter pioneered by Scott in 1973 interest in passive
      urethral compression disappeared in favor of the implantation of an inflatable
      circumferential prosthetic sphincter. Recently there has been a trend back to
      passive urethral compression. Synthetic bolsters have been described that
      passively compress the bulbar urethra to achieve urinary incontinence after
      radical prostatectomy. CONCLUSIONS: Much creativity has been dedicated to solve
      the complex and challenging problem of post-prostatectomy urinary incontinence.
      Devices used for treating this condition may be grouped according to the
      mechanism of action and how they are applied. Passive urethral compression, long
      abandoned in favor of dynamic implantable sphincters, has reemerged. Further
      research in this field may determine which school of thought may provide the best
      solution for treating post-prostatectomy urinary incontinence.

PMID- 11458039
TI  - Era specific biochemical recurrence-free survival following radical prostatectomy
      for clinically localized prostate cancer.
AB  - PURPOSE: We retrospectively reviewed a large series of men with clinically
      localized prostate cancer who underwent surgery to define the extent of stage
      migration and its influence on biochemical recurrence in 3 different eras of
      prostate cancer management. MATERIALS AND METHODS: A total of 2,370 men were
      treated with radical prostatectomy from 1982 to 1998. We analyzed the freedom
      from biochemical (prostate specific antigen) progression after radical
      prostatectomy. We compared the distribution of pathological stage by the year of
      surgery. We then compared the biochemical recurrence-free survival rate according
      to the different eras that reflect a change in prostate cancer management.
      RESULTS: There was a significant downward stage migration of prostate cancer and
      an increasing proportion of men who presented with organ confined disease in
      recent years. The actuarial biochemical recurrence-free rate was significantly
      different for patients who underwent surgery between 1982 and 1988, compared with
      those between 1989 and 1998 (p <0.001). These changes may have reflected the
      benefits of early detection with prostate specific antigen and digital rectal
      examination, better preoperative selection of patients for surgery as well as the
      effect of lead time. CONCLUSIONS: Widespread early detection programs for
      prostate cancer resulted in downward stage migration in men presenting with
      prostate cancer at our institution during the last 18 years. Also, we have
      demonstrated a biochemical recurrence-free survival advantage, probably secondary
      to an improved therapeutic outcome as well as lead time bias, in men who
      underwent surgery between 1989 and 1998, compared with those between 1982 and
      1988. When trying to compare the efficacy of different treatment modalities for
      prostate cancer, the era in which patients underwent therapy is an important
      factor to be considered.

PMID- 11458040
TI  - The bioavailability of oxalate from Oca (Oxalis tuberosa).
AB  - PURPOSE: It is believed that soluble oxalate has higher bioavailability than
      insoluble oxalate. Oca (Oxalis tuberosa) is moderately high in oxalate and
      contains oxalate in soluble form only. We estimated the bioavailability of
      oxalate in oca based on the urinary excretion of oxalate after oxalate loading
      with oca to estimate the bioavailability of oxalate in oca. We also clarified
      whether bioavailability differs in various oxalate loads from the same food
      source and studied the effect of an additional calcium source on the
      bioavailability of oxalate from oca. MATERIALS AND METHODS: Four men and 4 women
      ingested 50, 100 and 150 gm. oca as well as 100 gm. oca with 100 gm. sour cream.
      Oxalate was measured in a 6-hour urine sample from each volunteer. RESULTS: The
      mean bioavailability of oxalate from oca plus or minus standard deviation was
      1.44% +/- 1.31% during the 6-hour period after intake. There was no significant
      difference in oxalate bioavailability among oxalate intake levels in this study,
      although oca consumption with sour cream significantly decreased the uptake of
      oxalate (p <0.01). The variation in bioavailability among individuals was high in
      our study. CONCLUSIONS: The bioavailability of oxalate in oca appears to be
      similar to that in spinach. However, bioavailability varies among individuals and
      depends on other constituents of a combined meal.

PMID- 11458041
TI  - Differences in urine volume and supersaturation in 2 physician networks.
AB  - PURPOSE: We determined whether a network of practices devoted to a broad range of
      urological care would achieve a decrease in metabolic stone risk comparable to
      that achieved by a network of similar practices that emphasized kidney stone
      management as a distinct specialized interest, provided that each was given
      equivalent access to high level urine testing and software support. MATERIALS AND
      METHODS: Pretreatment and treatment 24-hour urine samples were obtained from
      patients in a large network of practices related by the shared use of lithotripsy
      facilities and instruments (group 2) and a contrasting network of practices that
      emphasize stone treatment over other concerns (group 1). All known urine risk
      factors, including supersaturation, were measured and calculated. RESULTS:
      Treatment supersaturation values in group 2 exceeded those in group 1. The reason
      was unpredicted and unexplained but highly consistent lower urine volume in group
      2 patients that was present before and persisted during treatment. Group 2
      physicians mostly achieved changes in urine volume and stone risk factors
      equivalent to those of group 1 physicians but began with higher supersaturation
      due to lower urine volume. CONCLUSIONS: A network of physicians not specialized
      for stone care may achieve a decreased risk equivalent to that of more
      specialized physicians. Initial patient characteristics may vary significantly in
      the groups for reasons that are unknown to date, greatly affecting treatment
      outcome.

PMID- 11458042
TI  - The case for laparoscopic adrenalectomy.
AB  - PURPOSE: The current status of laparoscopic adrenal surgery was assessed.
      MATERIALS AND METHODS: A current MEDLINE search revealed 308 articles pertaining
      to laparoscopic surgery of the adrenal gland. Based on this literature review
      laparoscopic surgical anatomy, current indications and contraindications, and
      laparoscopic techniques were identified. The role of laparoscopic surgery for
      various adrenal disorders, including aldosteroma, pheochromocytoma, Cushing's
      syndrome, incidentaloma and adrenal cancer, were evaluated. Studies specifically
      comparing open versus laparoscopic adrenalectomy and the financial implications
      of laparoscopy were evaluated. Furthermore, newer advances in the minimally
      invasive management of surgical adrenal disease were identified. RESULTS:
      Available data from multiple institutions imply that laparoscopic adrenal surgery
      is safe and efficacious for aldosteroma, pheochromocytoma, Cushing's disease and
      incidentaloma. Compared to open surgery laparoscopy provides equally effective
      treatment, while minimizing patient morbidity. Laparoscopic adrenalectomy is
      financially superior to open adrenalectomy. For adrenal cancer open surgery
      currently remains the treatment of choice. CONCLUSIONS: In the majority of
      patients with surgical adrenal disease except those with adrenal cancer
      laparoscopy may now be considered an established treatment modality.

PMID- 11458043
TI  - Comparison of 3 surgical approaches to laparoscopic adrenalectomy: a
      nonrandomized, background matched analysis.
AB  - PURPOSE: To clarify the characteristics of surgical approaches to laparoscopic
      adrenalectomy we performed background matched analysis of clinical outcomes of
      the 3 approaches. MATERIALS AND METHODS: From February 1992 to July 2000 we
      performed 118 laparoscopic adrenalectomies in 115 patients with adrenal tumors.
      For these operations we used the anterior transperitoneal approach in 46
      patients, the lateral transperitoneal approach in 32 and the lateral
      retroperitoneal approach in 40. RESULTS: To exclude the learning curve effect we
      eliminated our initial 20 patients treated with the anterior transperitoneal
      approach. To allow background matching of the 3 groups we also excluded 14
      patients with tumors more than 5 cm., 6 who underwent conversion to open surgery
      and 1 patient who required 5 days of bed rest for retroperitoneal hematoma caused
      by bleeding from a trocar port. The final analysis included 16, 25 and 36 cases
      managed via the anterior transperitoneal, lateral transperitoneal and lateral
      retroperitoneal approach, respectively. Average operative time was significantly
      shorter for the lateral transperitoneal approach. Postoperative recovery was not
      significantly different in the lateral transperitoneal and lateral
      retroperitoneal groups. Postoperative complications included mild paralytic ileus
      in 2 patients and shoulder tip pain, probably peritoneal irritation due to carbon
      dioxide insufflation and bowel preparation, in 4 in the transperitoneal groups.
      Our results imply that the easiest procedure is the lateral transperitoneal
      approach but the lateral retroperitoneal approach is slightly less invasive.
      CONCLUSIONS: Although it is important to remember that this study was not a
      prospective randomized trial and, thus, had from certain biases, we believe that
      if a tumor is more than 5 cm. and/or the surgeon is not yet skilled in
      laparoscopic adrenalectomy, the lateral transperitoneal approach is the most
      suitable method. If the surgeon has performed at least 20 operations, the adrenal
      tumor is unilateral and the lesion is less than 5 cm., the lateral
      retroperitoneal approach seems to be more suitable because of its minimally
      invasive nature. The lateral retroperitoneal approach is also preferred in
      patients with a history of upper abdominal surgery. With improvements in
      technique and new instruments the time required for the lateral retroperitoneal
      approach has been significantly decreased.

PMID- 11458044
TI  - Hand assisted laparoscopic donor nephrectomy: a comparison with the open
      approach.
AB  - PURPOSE: Hand assisted laparoscopy combines aspects of open and laparoscopic
      surgery. A hand in the abdomen may facilitate laparoscopic live donor
      nephrectomy, allowing more urologists to participate. We report and compare our
      initial series of hand assisted laparoscopy donor nephrectomy with nephrectomy
      performed by standard open methods. MATERIALS AND METHODS: In the last 18 months
      60 patients at 2 institutions underwent hand assisted laparoscopy donor
      nephrectomy. This cohort was compared to a contemporary group of 31 patients who
      underwent open donor nephrectomy via a flank incision at our 2 institutions.
      Demographic and outcome data were compared retrospectively in a nonrandomized
      fashion in the 2 groups. RESULTS: Demographic data on patient age, male-to-female
      ratio and body mass index were similar in the 2 groups. Operative time,
      transfusion rate, time to oral intake and complications were also similar.
      However, estimated blood loss, change in hematocrit preoperatively to
      postoperatively, hospitalization, parenteral and oral narcotic requirement, and
      donor convalescence were significantly less in the hand assisted laparoscopy
      versus open groups. In terms of allograft function, nadir creatinine, time to
      nadir creatinine, creatinine clearance at 6, 12, and 18 months, delayed graft
      function, episodes of acute rejection and ureteral stricture were similar in the
      groups. CONCLUSIONS: Hand assisted laparoscopy is safe, efficacious and
      reproducible for living related donor nephrectomy. Compared with the open
      technique hand assisted laparoscopy provides the donor with significantly
      decreased postoperative morbidity, while enabling excellent allograft function.
      Further randomized prospective studies are warranted.

PMID- 11458045
TI  - Long-term followup after laparoscopic nephropexy for symptomatic nephroptosis.
AB  - PURPOSE: Symptomatic nephroptosis is a rare disease requiring surgical therapy
      only in select cases. Laparoscopic nephropexy has been reported as minimally
      invasive treatment for symptomatic patients. We evaluated our long-term outcome
      after laparoscopic fixation of the kidney with an alloplastic mesh graft.
      MATERIALS AND METHODS: Since 1992, 30 patients have undergone laparoscopic
      transperitoneal nephropexy for symptomatic nephroptosis. All patients were
      preoperatively investigated by excretory urography (IVP) and split renal scan in
      the supine and upright positions. For fixing the kidney to the abdominal wall a
      polyglactin and polypropylene mesh graft was used in 6 and 24 cases,
      respectively. A total of 17 patients with a minimum followup of 5 years
      participated in an assessment of long-term outcome. Clinical examination, IVP and
      split renal function testing were performed with patients lying and standing.
      Patients were further questioned about postoperative satisfaction and whether
      they would undergo the procedure again. RESULTS: Of 17 patients 10 completed all
      investigations, 3 were contacted by telephone and 4 were lost to followup. Median
      followup was 5.9 years. Improvement in symptoms was reported in all cases with
      complete relief in 11 and intermittent flank pain requiring no medication in 2.
      There were no postoperative urinary tract infections or hematuria observed with
      improved hypertension requiring no postoperative medication in 1 case.
      Postoperatively IVP showed no recurrence in 8 of 10 patients but there was 5 cm.
      or greater recurrent ptosis in 2. Recurrence developed after using the
      polyglactin and polypropylene mesh grafts. Comparing preoperative and
      postoperative (123)iodine renal scans revealed significant improvement in renal
      function in 9 cases (p <0.05). There was no postoperative difference in split
      renal function and only 1 patient did not improve. No complications were noted
      except 1 symptomatic recurrence 3 months after the initial operation that
      required open surgical fixation. A total of 11 patients were completely satisfied
      with the long-term outcome and 2 were moderately satisfied. Of the patients 12
      would undergo the procedure again, including 2 with persistent slight flank pain.
      One patient was inconsistent in regard to whether she would undergo the procedure
      again. CONCLUSIONS: Symptomatic nephroptosis is a bothersome disease requiring
      therapy only after thorough evaluation, including IVP and split renal scan with
      patients supine and upright. The good clinical outcome and highly satisfactory
      cosmetic result support laparoscopic nephropexy as the treatment of choice. Short
      term and long-term results prove the efficacy of renal fixation with alloplastic
      mesh graft as minimally invasive therapy with a high success rate.

PMID- 11458046
TI  - Stage pT1 conventional (clear cell) renal cell carcinmoa: pathological features
      associated with cancer specific survival.
AB  - PURPOSE: The features predictive of aggressive behavior in stage pT1 conventional
      (clear cell) renal cell carcinoma are not completely known. We evaluated
      pathological features in a large series of stage pT1 conventional renal cell
      carcinoma cases and examined the association of these features with cancer
      specific survival. MATERIALS AND METHODS: Patients with solitary stage pT1
      conventional renal cell carcinoma who underwent radical nephrectomy between 1970
      and 1997 were eligible for study. For each of the 46 patients who died of renal
      cell carcinoma we selected a stratified random sample of at least 3 year matched
      controls who were still alive or dead of other causes. The study included 277
      patients. We evaluated patient age at nephrectomy, sex, tumor size, Fuhrman
      grade, necrosis and sarcomatoid component. Univariate and multivariate Cox
      proportional hazards models were fit to assess the features associated with
      cancer specific survival. RESULTS: Multivariate modeling revealed that tumor
      size, Fuhrman grade and necrosis were jointly significantly associated with
      cancer specific survival. Of the 4.5, 5 and 6 cm. tumor size cutoffs examined on
      univariate analysis a cutoff of 5 cm. or greater was most predictive of cancer
      specific survival. CONCLUSIONS: In stage pT1 conventional renal cell carcinoma
      Fuhrman grade, tumor necrosis and tumor size together were jointly significantly
      associated with cancer specific survival. Specifically of the tumor size cutoffs
      analyzed the 5 cm. cutoff was most predictive of cancer specific survival.

PMID- 11458047
TI  - Clinical significance of denuded urothelium in bladder biopsy.
AB  - PURPOSE: Although to our knowledge the significance of denuded urothelium in
      bladder biopsies has not been studied previously, it is thought to be a problem
      because benign urothelial cells are cohesive and not expected to shed into the
      urine. We correlated the pertinent clinical features of patients with denuded
      bladder biopsies and/or specific pathological features of denuded bladder biopsy
      specimens with patient outcome in regard to bladder lesions to help predict the
      subsequent likelihood of diagnosing bladder carcinoma in a patient with a
      nondiagnostic denuded biopsy. MATERIALS AND METHODS: We studied 51 denuded
      bladder biopsies from 44 patients in which the average extent of epithelial
      denudation was 90%. RESULTS: Of the 27 male (69%) and 17 female (31%) patients 22
      to 86 years old (mean age 62) 34% had no history of bladder neoplasms. In
      remainder there were flat carcinoma in situ with or without other tumors (26%),
      high (20%) and low (14%) grade papillary tumors without carcinoma in situ and
      miscellaneous conditions (6%). Overall 31% of patients were diagnosed with
      carcinoma in situ within 24 months (median 5.5) after the denuded specimen was
      obtained. Parameters that did not correlate with the subsequent diagnosis of
      carcinoma in situ included cystoscopic impression, history of intravesical
      chemotherapy, sex, age, tissue inflammation, percent of tissue fragments with any
      denudation, number of denuded tissue fragments and percent of overall denuded
      epithelium. A history of carcinoma in situ before denuded biopsy predicted a
      diagnosis of carcinoma in situ within 24 months after denuded biopsy in 54% of
      patients in contrast to 19% of those without a history of carcinoma in situ (p =
      0.03). Factoring in a history of other bladder tumor types in various
      combinations did not predict carcinoma in situ after denuded biopsy. The other
      predictive factor was cold cup biopsy. Carcinoma in situ developed within 24
      months in 45% of patients in whom the denuded specimen was obtained by cold cup
      biopsy in contrast to none who underwent hot wire loop biopsy (p = 0.007). Cold
      cup biopsy and a history of carcinoma in situ were independently predictive.
      Carcinoma in situ developed within 24 months in 75% of patients with a history of
      that condition and a subsequent cold cup biopsy showing denuded epithelium.
      However, only 29% of those who underwent cold cup biopsy and had no history of
      carcinoma in situ were diagnosed with carcinoma in situ. CONCLUSIONS: In bladder
      biopsies obtained by a hot wire loop denudation most likely results from thermal
      injury when there is a low risk of subsequent carcinoma in situ. When the denuded
      biopsy sample was obtained by cold cup biopsy, particularly when associated with
      a history of carcinoma in situ, most cases represent neoplastic cell denudation
      and a high risk for subsequent carcinoma in situ.

PMID- 11458048
TI  - Chemosensitization of bladder carcinoma cells by bcl-xL antisense
      oligonucleotides.
AB  - PURPOSE: We investigated antisense inhibition of anti-apoptotic bcl-xL and bcl-2
      proteins to increase chemosensitization in the T24 and 5637 bladder carcinoma
      cell lines. MATERIALS AND METHODS: A T24 bladder carcinoma cell line stably over
      expressing bcl-xL protein was constructed. Apoptosis by cytotoxic agents was
      estimated by cell cycle analysis and Annexin V binding. To eliminate bcl-xL
      expression T24 and 5637 cells were treated with C5-propynylated and 2'-O
      methylribo-oligonucleotides. Levels of protein and messenger RNA were measured by
      Western and Northern blot analysis. Cell viability after combined treatment with
      oligonucleotides and various cytotoxic agents was measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and evaluated
      statistically by Student's 2-sample t test. RESULTS: Forced over expression of
      bcl-xL protein desensitized the T24 bladder carcinoma cell line to cytotoxic
      agents. C5-propynylated and 2'-O-methylribo-oligonucleotides down-regulated bcl
      xL protein expression in the T24 and 5637 cell lines, and increased their
      sensitivity to cytotoxic agents. The efficiency of antisense down-regulation of
      bcl-xL protein expression depended on the type of delivery agent. CONCLUSIONS:
      Antisense down-regulation of bcl-xL protein sensitizes bladder carcinoma cells to
      cytotoxic agents. However, it is possible that cellular chemosensitization
      results from a combination of effects, including nonsequence specificity,
      irrelevant cleavage and effects of the carriers combined with the specific
      antisense effects.

PMID- 11458049
TI  - Comparative evaluation of the diagnostic performance of the BTA stat test, NMP22
      and urinary bladder cancer antigen for primary and recurrent bladder tumors.
AB  - PURPOSE: We compared overall sensitivity and specificity of the urinary bladder
      cancer antigen enzyme-linked immunosorbent assay (UBC, IDL Biotech, Sollentuna,
      Sweden), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and
      NMP22 test kit (Matritech, Newton, Massachusetts), and the differential
      sensitivity regarding the histological pattern of tumors. MATERIALS AND METHODS:
      A total of 213 patients with clinical and/or imaging signs of bladder cancer
      provided a single voided urine sample for the bladder cancer antigen, BTA stat
      test and NMP22 before cystoscopy. Of these patients 95 were monitored for
      superficial bladder cancer, while the remaining 118 had no history of bladder
      cancer. All detected bladder tumors or suspicious lesions were resected
      transurethrally. A group of 21 age and sex matched healthy volunteers were also
      evaluated with the same tests. RESULTS: Bladder cancer was confirmed
      histologically in 118 patients, of whom primary and recurrent tumors were in 68
      and 50, respectively. The optimal cutoffs calculated with receiver operating
      characteristics curves were 8 units per ml. for NMP22 and 12 microg./l. for
      bladder cancer antigen. Overall sensitivity and specificity were 72.9% and 64.6%
      for the BTA stat test, 63.5% and 75.0% for NMP22, and 80.5% and 80.2%,
      respectively, for bladder cancer antigen. Bladder cancer antigen proved
      significantly more sensitive than NMP22 for detecting bladder cancer (p = 0.001)
      but not more than the BTA stat test, while the specificity of it was
      significantly higher than that of the BTA stat test (p = 0.009). Bladder cancer
      antigen had a sensitivity of 80.7% for stage Ta tumors, which was significantly
      higher than NMP22 (52.6%, p = 0.001) and the BTA stat test (57.9%, p = 0.01). In
      grade I tumors the sensitivity of bladder cancer antigen (70%) did not differ
      significantly than that of the BTA stat test (50%) and NMP22 (50%, p = 0.14).
      Bladder cancer antigen had the least false-positive results in patients with a
      history of bladder cancer and negative cystoscopy, and those with urological
      disease other than bladder cancer. CONCLUSIONS: Our data indicate that bladder
      cancer antigen may be a more potent diagnostic marker for bladder cancer than
      NMP22 and the BTA stat test based on the higher sensitivity for detecting low
      stage and low grade tumors, and the higher specificity. The contribution of these
      tests for detection of bladder cancer should still be considered adjunctive to
      cystoscopy.

PMID- 11458050
TI  - Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus
      Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary
      carcinoma of the bladder: a European Organization for Research and Treatment of
      Cancer genito-urinary group randomized phase III trial.
AB  - PURPOSE: After transurethral resection, we compared the efficacy and side effects
      of weekly intravesical instillations of epirubicin, bacillus Calmette-Guerin
      (BCG), and BCG plus isoniazid during a 6-week interval followed by 3 weekly
      maintenance instillations at months 3, 6, 12, 18, 24, 30 and 36 in patients with
      intermediate and high risk Ta, T1 bladder cancer. MATERIALS AND METHODS: A total
      of 957 patients were randomized at 44 institutions in a phase III multicenter
      trial. RESULTS: The time to first recurrence was significantly longer in patients
      treated with BCG and BCG plus isoniazid compared to epirubicin (p = 0.0001) but
      there was no difference between the 2 BCG regimens (p = 0.27). Progression to
      muscle invasive cancer was rare (5%) and did not differ significantly among the 3
      arms (p = 0.12). Drug induced cystitis was observed in 31% of the patients
      treated with epirubicin, 42% BCG and 45% BCG plus isoniazid. Systemic side
      effects, such as fever and malaise, were not observed in patients treated with
      epirubicin, but were noted in 31% BCG and 36% BCG plus isoniazid. CONCLUSIONS:
      Intravesical BCG with or without isoniazid provokes more side effects than
      epirubicin. Prophylactic isoniazid does not reduce the side effects of BCG, while
      BCG with or without isoniazid prolongs the time to first recurrence compared to
      epirubicin. Further followup is required before long-term conclusions can be made
      for progression-to-muscle invasive disease and survival.

PMID- 11458051
TI  - Functional p53 mutation as a molecular determinant of paclitaxel and gemcitabine
      susceptibility in human bladder cancer.
AB  - PURPOSE: Paclitaxel and gemcitabine are promising new agents for treatment of
      human bladder cancer. We determine how the presence or absence of p53 function
      impacts the cytotoxic effects of these chemotherapeutic agents in human bladder
      cancer. MATERIALS AND METHODS: The J82 human bladder cancer (TCC) cell line was
      transfected with a temperature sensitive p53 (tsp53) mutant that functions as
      mutated p53 at 37C but functions as wild-type (normal) p53 at 32C. Susceptibility
      of these inducible p53 TCC cells to paclitaxel and gemcitabine induced
      cytotoxicity was evaluated and kill significance determined between sub-lethal
      and lethal doses. RESULTS: Significant paclitaxel dose dependent cytotoxicity was
      observed in J82 TCC cells lacking normal p53 and tsp53 transfected cells at 37C,
      which was the mutant p53 temperature in transfectants between maximal and minimal
      kill concentrations for either (p <0.001). Likewise, significant cytotoxicity was
      observed in parental J82 TCC at 32C (p <0.001), while restoration of p53 function
      in tsp53 transfected cells on shift to 32C abrogated significant dose dependent
      cytotoxicity. Gemcitabine caused significant cell death in the cell lines
      incubated at either temperature and, thus, was equally effective regardless of
      cellular p53 function (p <0.001, respectively). CONCLUSIONS: Paclitaxel requires
      functionally mutated p53 to induce cell death in human bladder cells, indicating
      that it may be more effective against TCC with p53 mutations than against TCC,
      which lacks p53 abnormalities, while gemcitabine is effective regardless of p53
      function. These findings provide a rationale for selecting chemotherapy based on
      the p53 status of individual bladder cancers.

PMID- 11458052
TI  - Bladder tumor markers, intravesical therapy and systemic chemotherapy.

PMID- 11458053
TI  - Clinical under staging of high risk nonmuscle invasive urothelial carcinoma
      treated with radical cystectomy.
AB  - PURPOSE: The role of radical cystectomy in patients with nonmuscle invasive
      urothelial carcinoma of the bladder remains controversial. The risk of
      overtreatment must be balanced against the potential benefit of aggressive
      therapy. We reviewed our results in these patients with a particular emphasis on
      clinical under staging. MATERIALS AND METHODS: We reviewed the records of 214
      consecutive patients who underwent radical cystectomy for urothelial carcinoma
      between April 1995 and August 1999, focusing on those with nonmuscle invasive,
      stages T1 or less disease. We assessed clinical and pathological data as well as
      outcomes based on pathological disease extent. RESULTS: A total of 78 patients
      (36%) underwent radical cystectomy for clinical stages T1 or less disease.
      Indications included disease refractory to intravesical therapy in 29 cases
      (37%), pathological findings reflective of high grade stage T1 or multifocal
      disease in 26 (33%), radiographic suspicion of invasive disease in 15 (20%) and
      severe symptoms in 8 (10%). Cancer was clinically under staged with stages pT2 or
      greater disease in 31 patients (40%) according to final pathology results. Under
      staging was most pronounced in the 10 patients (67%) with suspicious radiography
      and in the 18 (64%) with absent muscle in the biopsy specimen. Of the 78 patients
      with pathological stages pT1 disease or less 98% had no evidence of disease
      compared to 65% with stages pT2 or greater disease (p <0.01). CONCLUSIONS:
      Despite the intent to perform early cystectomy a significant percent of patients
      harbored occult muscle invasive and/or metastatic disease. In clinical and
      pathological, superficial stages T1 or less cases disease-free survival was
      excellent. Due to these results, the selection of high risk superficial
      transitional cell carcinoma cases for continued bladder sparing treatment should
      include uninvolved muscle on biopsy and absent radiographic suspicion of
      invasion.

PMID- 11458054
TI  - Long-term treatment related complications of brachytherapy for early prostate
      cancer: a survey of patients previously treated.
AB  - PURPOSE: We determined long-term symptoms in patients after brachytherapy
      (radioactive seed implantation) for early (nonmetastatic) prostate cancer.
      MATERIALS AND METHODS: We performed a cross-sectional survey of 105 (80% of those
      contacted) men treated at least 2 years 9 months (median 5.2 years) previously
      with brachytherapy alone (72 patients) or brachytherapy plus external beam
      radiation therapy (33) at a pioneering referral center for ultrasound guided
      brachytherapy. RESULTS: Median patient age was 70 years at treatment and 75 years
      when surveyed. Bowel symptoms were uncommon (range 4% to 9%) unless patient had
      also received external beam radiation therapy. Urinary incontinence occurred in
      45% of men, although leakage of more than a few drops, daily leakage and wearing
      absorptive pads occurred in 11%, 11% and 16%, respectively. Men who underwent
      documented transurethral prostatic resection were much more likely to report
      incontinence (83% versus 39%, p = 0.005) and those who underwent implantation
      less than 5 years earlier were less likely (33% versus 53%, respectively, p =
      0.04). Complete impotence was common (50%) but impaired erections were more so
      (73%). Patients who received combined radiation treatment had more frequent
      erectile dysfunction. CONCLUSIONS: Long-term bowel symptoms are infrequent after
      brachytherapy alone. Urinary incontinence is common, although usually only a few
      drops and not daily. Erectile dysfunction, prevalent in populations of older men,
      was found in most men. However, because our study design precluded documenting
      baseline symptoms before treatment and subsequent clinical interventions, the
      contribution of factors other than brachytherapy is unclear. The morbidity of
      patients receiving more recent brachytherapy may be less.

PMID- 11458055
TI  - Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy
      before radical prostatectomy: biochemical and pathological effects.
AB  - PURPOSE: A prospective phase 3 trial was initiated to determine whether 8
      compared with 3-month neoadjuvant hormonal therapy reduces prostate specific
      antigen (PSA) recurrence rates after radical prostatectomy. Our interim analysis
      includes secondary end points of differences in biochemistry, pathology and
      adverse events between the 2 groups. MATERIALS AND METHODS: Men with clinically
      confined prostate cancer were randomized to receive 7.5 mg. leuprolide
      intramuscularly monthly and 250 mg. flutamide orally 3 times daily for 3 or 8
      months before radical prostatectomy. Our study was powered to detect a 35%
      decrease in PSA recurrence, assuming a 30% recurrence rate in the 3-month arm
      after 3 years. RESULTS: A total of 547 men were randomized between August 1995
      and April 1998. Men in the 8 and 3-month groups were equally stratified for T
      stage (29% T1c, 70% T2), Gleason grade (68% less than 4, 32% 4 or greater) and
      pretreatment PSA (63% less than 10, 27% 10 to 20 and 10% greater than 20
      microg./l.). Mean pretreatment PSA was slightly higher in the 8-month compared
      with the 3-month group (11.64 versus 9.95 microg./l., respectively, p = 0.0539).
      A total of 44 men withdrew from study before surgery and, therefore, were
      nonevaluable. Preoperative PSA nadir was less than 0.1 microg./l. in 43.3% versus
      75.1% (p <0.0001), and 0.3 microg./l. or greater in 21% versus 9.2% after 3
      versus 8 months, respectively (p <0.0006). Mean serum PSA decreased 98% to 0.12
      microg./l. after 3 months, with a further 57% to 0.052 microg./l. from 3 to 8
      months. Transrectal ultrasound determined that prostatic volume decreased 37%
      from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy (p =
      0.0001) and a further 13% to 22.2 cc after 8 months (p = 0.03). Mean hemoglobin
      decreased 15% (148.2 to 125.4 gm./dl.) after 3-month neoadjuvant hormonal therapy
      but stabilized thereafter. Radical prostatectomy was completed in 500 men, while
      surgery was aborted intraoperatively in 3. Positive margin rates were
      significantly lower in the 8 than 3-month group (12% versus 23%, respectively, p
      = 0.0106). There were no fatal adverse events and no differences between the 2
      groups in the severity or causality (p = 0.287, 0.0564) of adverse events, or
      incidence of increased liver enzymes or diarrhea (p = 0.691, 0.288,
      respectively). However, men in the 8-month group noticed a higher number of newly
      reported adverse events (4.5 versus 2.9, p <0.0001) and higher incidence of hot
      flushes than the 3-month group (87% versus 72%, respectively, p <0.0001).
      CONCLUSIONS: Ongoing biochemical and pathological regression of prostate tumors
      occurs between 3 and 8 months of neoadjuvant hormonal therapy, suggesting that
      the optimal duration of neoadjuvant hormonal therapy is longer than 3 months.
      Longer followup is needed to determine whether longer therapy alters PSA
      recurrence rates.

PMID- 11458056
TI  - A structured debate: immediate versus deferred androgen suppression in prostate
      cancer-evidence for deferred treatment.
AB  - PURPOSE: We present a structured debate supporting the premise that immediate
      hormonal intervention has not been conclusively shown to provide a survival
      advantage in the management of advanced prostate cancer. MATERIALS AND METHODS:
      The literature emphasizing randomized trials was reviewed. Recommendations are
      based solely on a demonstrated advantage in survival. RESULTS: In patients with
      stage Tx Nx Mo or MI disease who did not receive other primary therapy there is
      no demonstrated survival advantage to immediate hormonal therapy. In men with
      positive lymph nodes who underwent radical prostatectomy a relatively small study
      showed a survival advantage in favor of immediate hormonal treatment compared to
      deferred treatment. This study did not reach the projected accrual of 240
      patients and results have not been supported by other trials. In men with stages
      T2-4 Nx Mx disease who underwent primary treatment with radiotherapy a survival
      advantage for early hormonal therapy is primarily limited to high risk subgroups.
      In patients with biochemical relapse following primary treatment there are no
      trials. CONCLUSIONS: Because hormonal therapy is associated with the development
      of irreversible resistance in virtually all patients, it does not cure, there is
      usually a long interval from first prostate specific antigen elevation to the
      development of metastatic disease, and hormonal therapy has profound side effects
      and is expensive, delayed treatment is recommended in men with biochemical
      relapse following surgery or radiotherapy. Patients should be strongly encouraged
      to enter clinical trials to answer this question.

PMID- 11458057
TI  - Prospective evaluation of hot flashes during treatment with parenteral estrogen
      or complete androgen ablation for metastatic carcinoma of the prostate.
AB  - PURPOSE: We evaluated the incidence and frequency of, and distress due to hot
      flashes after castration therapy with polyestradiol phosphate and complete
      androgen ablation. MATERIALS AND METHODS: A total of 915 men with metastatic
      prostate carcinoma enrolled in the Scandinavian Prostatic Cancer Group-5 trial
      study were randomized to intramuscular injections of 240 mg. Polyestradiol
      phosphate every 2 weeks for 8 weeks followed by monthly subcutaneous injections
      or complete androgen ablation, that is bilateral orchiectomy or 3.75 mg. of the
      gonadotropin-releasing hormone analog triptorelin monthly combined with 250 mg.
      of the antiandrogen flutamide 3 times daily. The incidence and frequency of, and
      distress due to hot flashes were recorded at regular intervals using a
      questionnaire. RESULTS: Of the 915 men 901 were evaluated at a median followup of
      18.5 months. The incidence of hot flashes was 30.1% and 74.3% in the
      polyestradiol phosphate and complete androgen ablation groups, respectively (p
      <0.001). In the polyestradiol phosphate group the frequency of and distress due
      to hot flashes were significantly lower than in the androgen ablation group.
      There was complete relief from hot flashes in 50% of the men on polyestradiol
      phosphate during followup compared with none on androgen ablation. The incidence
      of hot flashes did not differ in men with and without tumor progression.
      CONCLUSIONS: Endocrine treatment with polyestradiol phosphate induced fewer and
      less distressing hot flashes than complete androgen ablation. Flashes also
      disappeared to a greater extent during polyestradiol phosphate than during
      androgen ablation. The data in this study enable us to provide thorough
      individual information to patients on the risk and grade of expected distress and
      duration of hot flashes during polyestradiol phosphate or complete androgen
      ablation treatment.

PMID- 11458058
TI  - Adult prostate sarcoma: the M. D. Anderson Cancer Center Experience.
AB  - PURPOSE: Sarcoma of prostate origin is rare. Historically, long-term survival
      rates for adult patients with prostate sarcoma are poor. We analyzed the
      experience of 1 institution with prostate sarcoma during the last 3 decades.
      MATERIALS AND METHODS: The records of 21 patients with prostate sarcoma were
      reviewed to identify symptoms at presentation, diagnostic procedures, presence
      and development of metastases, staging evaluation, histological subtype, grade
      and size of the primary tumor, and treatment sequence, including surgery, and
      preoperative and postoperative therapies. Several clinicopathological variables
      were assessed for prognostic importance. RESULTS: Most patients presented with
      urinary obstruction. The diagnosis of prostate sarcoma was usually established
      with ultrasound guided biopsy or transurethral resection. Histological subtypes
      were leiomyosarcoma in 12, rhabdomyosarcoma in 4, malignant fibrous histiocytoma
      in 1 and unclassified sarcoma in 4 patients. At last followup, 8 patients had no
      evidence of disease after a median of 81.5 months (range 10 to 197). The
      remaining 13 patients died of sarcoma (median survival 18 months, range 3 to 94).
      The 1, 3 and 5-year actuarial survival rates for all 21 patients were 81%, 43%
      and 38%, respectively. Factors predictive of long-term survival were negative
      surgical margins (p = 0.0005) and absence of metastatic disease at presentation
      (p = 0.0004). Tumor size and grade, and the histological subtype of prostate
      sarcoma had no significant influence on actuarial survival. CONCLUSIONS: The long
      term disease specific survival rate for adults with prostate sarcoma is poor.
      Early diagnosis and complete surgical resection offer patients the best chance
      for cure.

PMID- 11458059
TI  - Surgeon experience with penile fracture.
AB  - PURPOSE: The experience of a single surgeon with a series of 34 penile fractures,
      including 29 corrected surgically and 5 managed conservatively, at 3 large inner
      city medical centers in an 11-year period is presented. Standard diagnostic and
      therapeutic modalities are described that have evolved with time. MATERIALS AND
      METHODS: Between 1989 and 1999, 34 patients 18 to 38 years old (mean age 27 at
      presentation) were evaluated after blunt trauma to the erect penis. The interval
      from injury to presentation was between 6 and 72 hours. Of these patients 32 and
      2 had been injured during sexual intercourse and masturbation, respectively.
      Surgery in 29 cases involved a degloving incision, and intraoperative evaluation
      of the corpora and urethra by radiography or saline injection. Five patients were
      treated conservatively for presumed penile fracture after they refused diagnostic
      confirmation and/or surgery. RESULTS: Injury involved unilateral and bilateral
      corporeal rupture in 25 and 3 cases, respectively, and urethral injury in 5.
      Urinalysis in 6 patients demonstrated microscopic hematuria with 5 to 10 red
      blood cells, although there were several false-negative urethrograms and
      cavernosograms. At followup 33 of the 34 patients available reported erection
      adequate for intercourse without erectile or voiding dysfunction, while 2
      reported mild to moderate curvature. CONCLUSIONS: A degloving procedure with a
      urethral catheter in place provides the best exposure and orientation. In
      addition, saline injection may demonstrate additional corporeal body and/or
      urethral pathology as well as assess the integrity of repair. Although surgical
      repair was not associated with serious sequelae, a small subgroup of patients
      with presumed penile fracture also had no sequelae.

PMID- 11458060
TI  - Oral intake of poppy seed: a reliable and simple method for diagnosing vesico
      enteric fistula.
AB  - PURPOSE: In up to 50% of patients with vesico-enteric fistula conventional
      diagnostic methods fail. We report a simple and low cost diagnostic method that
      involves the oral intake of poppy seed. MATERIALS AND METHODS: From 1994 to 1999,
      17 patients in whom vesico-enteric fistula was suspected underwent the poppy seed
      test. We administered 250 gm. poppy seed orally in the evening and the urinary
      excretion of poppy seed was evaluated during the next 2 days. RESULTS: Of the 17
      patients 11 excreted the black seeds in the urine for 2 days after oral intake of
      the seeds. The diagnosis was supported by conventional diagnostic methods in 9 of
      the 11 cases, while in the remaining 2 the poppy seed test was the only
      preoperative diagnostic procedure that proved the existence of a fistula. The
      diagnosis was confirmed by surgical exploration in all 11 patients. In the
      remaining 6 patients with a nonspecific complaint vesico-enteric fistula was
      excluded by conventional diagnostic techniques and by the success of nonoperative
      therapy. CONCLUSIONS: The oral intake of poppy seed is a simple and ready
      available method for diagnosing vesico-enteric fistula. It may support the
      surgeon decision when conventional diagnostic tools fail.

PMID- 11458061
TI  - Orthotopic bladder substitution after radical cystectomy: 5 years of experience
      with a novel personal modification of the ileal s pouch.
AB  - PURPOSE: We report a 5-year experience with 52 patients who underwent radical
      cystoprostatectomy for bladder cancer and orthotopic bladder substitution using a
      novel personal modification of the S pouch. MATERIALS AND METHODS: From September
      1995 to December 1999, 52 men 36 to 72 years old (mean age 63) underwent bladder
      substitution with an S pouch. They were followed until September 2000. The pouch
      was constructed with a 36 cm. segment of ileum with the whole length used for the
      reservoir. The ureters were directly anastomosed with one above the other in the
      mid segment of the pouch without any antireflux procedure. Complications were
      documented and classified as early or up to 3 months postoperatively and late,
      and further subdivided by the relationship to neobladder construction. Continence
      and voiding pattern were evaluated by personal interview and neobladder function
      was urodynamically assessed. Mean followup in our patients was 30 months.
      RESULTS: The most common of the 5 early and 9 late neobladder related
      complications were persistent urine leakage and reflux, respectively. There was
      no reflux greater than grade III in the 4 patients with reflux (5 refluxing
      ureters) and no functional disorders. We observed 12 early and 5 late
      complications unrelated to the neobladder. Open reoperation was required in 5
      cases. Good or satisfactory daytime and nighttime continence was reported by 95%
      and 88% of our patients, respectively. By year 1 postoperatively 91% of our
      patients voided at an interval of 3 to 5 hours during the day. Mean maximum
      neobladder capacity was 672 ml. and mean post-void residual was 30 ml. by year 3
      postoperatively. Two patients required self-catheterization once daily and mild
      hyperchloremia without acidosis developed in 2. CONCLUSIONS: The advantages of
      our modified S pouch are technical simplicity, substantially shorter operative
      time and decreased bowel length required. It is associated with an acceptable
      complication rate and functional parameters with subsequent patient satisfaction
      and good quality of life.

PMID- 11458062
TI  - Complications of ureteroscopy: analysis of predictive factors.
AB  - PURPOSE: Although overall and major complication rates of 10% to 20% and 0% to
      6%, respectively, have been observed in large series of ureteroscopy, to our
      knowledge no systemic analysis to determine factors predictive of these
      complications has been reported. MATERIALS AND METHODS: We retrospectively
      reviewed all ureteroscopies performed at our institution for calculous disease
      from January 1997 through September 1999. A total of 322 procedures were
      performed by 5 attending surgeons. Intraoperative and immediate postoperative
      complications were identified. Bivariate and multivariate analysis was performed
      to identify associated factors with ureteral perforation and postoperative
      complications as the dependent variables. RESULTS: Bivariate analysis showed a
      significant association of ureteral perforation with increased operative time (p
      = 0.0001). In addition, we noted a significant association of postoperative
      complications with stones in the kidney (p = 0.0004), operative time (p = 0.05)
      and decreased surgeon experience (p = 0.0035) as well as a trend toward
      significance for the type of ureteroscope used (p = 0.0609). In multivariate
      logistic regression models ureteral perforation remained highly associated with
      operative time (p = 0.0005) when controlling for the other factors. Similarly
      decreased surgeon experience and a stone in the kidney were predictive of
      postoperative complications when controlling for the other factors (p = 0.004).
      CONCLUSIONS: Longer duration of the ureteroscopic procedure is strongly
      associated with ureteral perforation. The likelihood of immediate postoperative
      complications is greater when renal calculi are treated and less when the surgeon
      is more experienced.

PMID- 11458063
TI  - Chronic sacral neuromodulation in patients with lower urinary tract symptoms:
      results from a national register.
AB  - PURPOSE: The Italian Register was created in February 1997 to collect the
      national results of sacral neuromodulation. All Italian centers at which sacral
      neuromodulation is performed were invited to participate in our study. We present
      the results from retrospective and prospective registers. MATERIALS AND METHODS:
      A total of 196 patients underwent permanent implantation of sacral
      neuromodulation and were enrolled in the Italian register. There were 18 males
      and 75 females in the retrospective, and 28 males and 75 females in the
      prospective studies. Student's t test was used to compare paired values, and the
      Wilcoxon rank sum and nonparametric tests were used when necessary. RESULTS: Mean
      incontinent episodes daily plus or minus standard deviation for patients with
      detrusor instability went from 5.4 +/- 3.9 to 1.1 +/- 1.6 (median 5 and 0,
      respectively) at 12-month followup (p <0.001). For idiopathic retention average
      residual volume decreased from 277 to 108 cc (median 287 and 80, respectively),
      and 50% of patients stopped catheterization and another 13% catheterized once
      daily at 1-year after implantation. With neurogenic voiding disturbances, the
      results fluctuated with time from a minimum of 33% to a maximum 66% of patients
      who did not catheterize at 6-month followup and 12 months after implantation,
      respectively. At 12-month followup, 50% of patients with hyperreflexia had less
      than 1 incontinent episode daily. The problem was completely solved in 66% of
      patients in the retention group. Of patients in the urge incontinent population
      39% were completely dry and 23% had less than 1 incontinent episode daily.
      CONCLUSIONS: Sacral neuromodulation is effective therapy for treating lower
      urinary tract symptoms resistant to less invasive therapy.

PMID- 11458064
TI  - Chronic sacral neuromodulation.

PMID- 11458065
TI  - Long-term continence and patient satisfaction after artificial sphincter
      implantation for urinary incontinence after prostatectomy.
AB  - PURPOSE: We assess long-term continence and patient satisfaction after
      implantation of the AMS Sphincter 800 (American Medical Systems, Minnetonka,
      Minnesota) in men who were incontinent after total and subtotal prostatectomy.
      MATERIALS AND METHODS: Patients who had an artificial urinary sphincter implanted
      for urinary incontinence after prostatectomy and a minimum of 20 months of
      followup were identified from a patient database. The medical records of these
      209 patients were reviewed, and a questionnaire was mailed. Telephone contact was
      attempted with patients who did not respond to the questionnaire. Of the 209
      patients 11 (5%) had undergone device removal, 34 (16%) were deceased and an
      additional 51 (24%) could not be contacted for followup. Our study group
      consisted of the 113 patients with artificial urinary sphincters who could be
      contacted for followup. Mean followup was 73 months (range 20 to 170). RESULTS:
      There were 4 (4%) patients who were dry and continent and 68 (60%) were
      incontinent using 0 to 1 pad daily. An additional 35 (31%) patients required 2 to
      3 pads daily and 5 (4%) used more than 3 daily. There were 14 (12%) patients who
      had undergone surgical revision of the device. Of the 113 patients 31 (28%) were
      very satisfied, 50 (45%) satisfied, 20 (18%) neutral, 7 (6%) dissatisfied and 4
      (4%) very dissatisfied. One patient was not using his device to control
      continence. CONCLUSIONS: Artificial urinary sphincter implantation offers men who
      are incontinent after prostatectomy a reasonable chance for obtaining long-term
      satisfactory urinary control, although complete continence is unusual.

PMID- 11458066
TI  - Detrusor instability in men: correlation of lower urinary tract symptoms with
      urodynamic findings.
AB  - PURPOSE: We evaluated the correlation of lower urinary tract symptoms suggestive
      of detrusor instability with urodynamic findings in men. MATERIALS AND METHODS:
      Enrolled in our prospective study were 160 consecutive neurologically intact men
      referred for urodynamic evaluation of persistent lower urinary tract symptoms.
      All patients had storage symptoms suggestive of detrusor instability. Patients
      were further clinically categorized according to the chief complaint of urge
      incontinence, frequency and urgency, nocturia or difficult voiding. The clinical
      and urodynamic diagnosis in all patients as well as specific urodynamic
      characteristics of those with detrusor instability were analyzed according to the
      these 4 clinical categories. RESULTS: Mean patient age was 61 +/- 15 years. The
      chief complaint was urge incontinence in 28 cases (17%), frequency and urgency in
      57 (36%), nocturia in 30 (19%) and difficult voiding in 45 (28%). Detrusor
      instability was diagnosed in 68 cases (43%). A higher incidence of detrusor
      instability was associated with urge incontinence than with the other clinical
      categories (75% versus 36%, p <0.01). Of the patients 109 (68%) had bladder
      outlet obstruction, including 50 (46%) with concomitant detrusor instability. The
      prevalence of bladder outlet obstruction was similar in all patients regardless
      of the chief complaint. All other urodynamic diagnoses were also similar in the 4
      clinical categories. The mean bladder volume at which involuntary detrusor
      contractions occurred were lower in patients with urge incontinence and frequency
      and urgency than in those with nocturia and difficult voiding (277.1 +/- 149.4
      and 267.7 +/- 221.7 versus 346.7 +/- 204.6 and 306.2 +/- 192.1 ml., respectively,
      not statistically significant, p = 0.07). CONCLUSIONS: Detrusor instability and
      bladder outlet obstruction are common in men with lower urinary tract symptoms.
      The symptom of urge incontinence strongly correlated with detrusor instability.
      Other lower urinary tract symptoms did not correlate well with any urodynamic
      findings. Therefore, we believe that an accurate urodynamic diagnosis may enable
      focused and more efficient management of lower urinary tract symptoms in men.

PMID- 11458067
TI  - The tension-free vaginal tape procedure in women with previous failed stress
      incontinence surgery.
AB  - PURPOSE: The tension-free vaginal tape procedure is an increasingly popular
      choice for treating female urinary stress incontinence. This ongoing,
      prospective, open label study presents the results of tension-free vaginal tape
      surgery at 1 year in women who have previously undergone unsuccessful stress
      incontinence surgery. MATERIALS AND METHODS: A total of 67 women with previous
      failed surgery for stress urinary incontinence underwent the tension-free vaginal
      tape procedure. Treatment outcome was categorized as cure, significant
      improvement or failure based on cystometry findings and urinary pad loss results
      at 3 months of followup, and on subjective questioning at 3 months and 1 year of
      followup. RESULTS: At 12 months 54 women (81%) were cured, 4 (6%) were
      significantly improved and 9 (13%) were no better. No serious morbidity was noted
      after the procedure. CONCLUSIONS: The tension-free vaginal tape procedure
      provides the prospect of a success rate similar to that of a conventional sling
      procedure in patients with previous failed surgery. It has a low rate of
      operative complications and postoperative morbidity.

PMID- 11458068
TI  - Nonbladder related symptoms in patients with interstitial cystitis.
AB  - PURPOSE: Clinical experience and epidemiological studies suggest that patients
      with interstitial cystitis have multiple nonbladder related symptoms. However, to
      our knowledge this finding has not been tested with a validated questionnaire and
      matched controls. With the University of Wisconsin scale, we compare the scores
      for patients with interstitial cystitis to those for control subjects. This
      validated questionnaire includes 7 bladder and 18 reference symptoms not related
      to the bladder. MATERIALS AND METHODS: A total of 35 female patients with
      interstitial cystitis and 35 age matched female controls completed the University
      of Wisconsin questionnaire. RESULTS: For the 7 bladder symptoms the difference
      between interstitial cystitis and control groups was extremely significant (p =
      0.0001). Patients with interstitial cystitis had higher scores than controls for
      2 reference symptoms, including other pelvic discomfort, backache, dizziness,
      chest pain, aches in joints, abdominal cramps, nausea, heart pounding and
      headache (p <0.01). However, they did not have higher scores for blind spots
      and/or blurred vision, numbness and/or tingling in fingers or toes, swollen
      ankles, feeling of suffocation, sore throat, cough, flu, nasal congestion and
      ringing in ears. The majority of patients with interstitial cystitis had a 0
      score for all but 2 of the reference symptoms. CONCLUSIONS: Patients with
      interstitial cystitis had increased scores for 9 reference symptoms but did not
      indiscriminately report high scores for generalized complaints. This result
      suggests that in some cases of interstitial cystitis the pathophysiology may
      affect other organ systems besides the bladder. Alternatively, some of these
      symptoms may result from changes in sleep pattern or other factors associated
      with interstitial cystitis.

PMID- 11458069
TI  - Prevalence and bothersomeness of lower urinary tract symptoms in benign prostatic
      hyperplasia and their impact on well-being.
AB  - PURPOSE: We established the prevalence and bothersomeness of symptoms and their
      impact on well-being in a large group of strictly selected men with lower urinary
      tract symptoms suggestive of benign prostatic hyperplasia (BPH). MATERIALS AND
      METHODS: Included in our study were 475 consecutive men who met the criteria of
      the International Consensus Committee on BPH and voided more than 150 ml. during
      uroflowmetry. International Prostate Symptom Scores and quality of life score
      were determined. We included the 7 bothersomeness questions of the Symptom
      Problem Index and the 4 of the BPH Impact Index of the American Urological
      Association Measurement Committee. These questions refer to the degree of
      bothersomeness caused by urinary problems and how they affect various health
      domains. RESULTS: The symptoms with the highest prevalence based on mean scores
      were weak urinary stream, frequency and urgency. Urgency, nocturia and hesitancy
      were the most bothersome symptoms. Patients were only discouraged from performing
      normal daily activity when the symptom index exceeded 20. Incomplete emptying and
      frequency bothersomeness correlated strongly, and weak urinary stream and
      hesitancy bothersomeness correlated weakly with all health and quality of life
      domains. CONCLUSIONS: Weak urinary stream, frequency and urgency were the most
      prevalent symptoms, while urgency, nocturia and hesitancy were the most
      bothersome symptoms. In contrast to weak urinary stream and hesitancy, the
      bothersomeness of incomplete emptying and frequency was strongly associated with
      well-being.

PMID- 11458070
TI  - Prevalence and independent risk factors for erectile dysfunction in Spain:
      results of the Epidemiologia de la Disfuncion Erectil Masculina Study.
AB  - PURPOSE: We determined the prevalence of and risks factors for erectile
      dysfunction in Spain in a cross-sectional study. MATERIALS AND METHODS: A total
      of 2,476 noninstitutionalized Spanish men 25 to 70 years old were interviewed at
      home and answered a self-administered questionnaire of 71 items, including 2
      instruments to define erectile dysfunction, a simple self-assessment question to
      estimate erectile function and the International Index of Erectile Function. Data
      on disease, medication and toxic habits were also obtained. RESULTS: With an
      overall participation rate of 75% the prevalence of erectile dysfunction
      according to the simple question was 12.1%. According to the erectile function
      domain of the International Index of Erectile Function the overall prevalence was
      18.9%. Several independent risk factors were significantly associated with the
      probability of erectile dysfunction. Some differences arose according to the tool
      used to define the condition. However, there was a strong relationship of patient
      age with frequency or severity no matter which instrument was used to define
      erectile dysfunction. Diabetes (age adjusted odds ratio 4), high blood pressure
      (odds ratio 1.58), high cholesterol (1.63), peripheral vascular disorder (2.63),
      lung disease (3.11), prostate disease (2.93), cardiac problems (1.79), rheumatism
      (2.37) and allergy (3.08) were significantly associated with erectile
      dysfunction. Drug intake, which respondents called medication for nerves and
      sleeping pills, correlated strongly (odds ratio 2.78 and 4.27, respectively), as
      did tobacco use (2.5) and alcohol consumption (1.53). CONCLUSIONS: This study
      provides data on the prevalence of and risks factors for erectile dysfunction in
      Spain. The relationship of erectile dysfunction with certain risk factors, such
      as cardiovascular risk factors and drugs intake, are well known and our study
      corroborates these associations. Other associations with erectile dysfunction,
      such as prostate disease, allergy and rheumatism, support findings in previous
      reports, although to our knowledge the pathophysiological mechanisms remain
      unclear. Estimating the strength of the association of erectile dysfunction with
      distinct risk factors in terms of odds ratios enabled us to identify the factors
      to pursue when seeking to prevent erectile dysfunction. Furthermore, the
      relationship of tobacco with erectile dysfunction, which has been controversial
      in previous series, was well characterized in our study.

PMID- 11458071
TI  - Evaluation of male sexual function by the International Index of Erectile
      Function after deep dorsal vein arterialization of the penis.
AB  - PURPOSE: The objective of vascular surgery for erectile dysfunction is to provide
      long-term improvement of erectile function. We evaluated that claim after deep
      dorsal vein arterialization by a cross-sectional study of multifaceted male
      sexual function with the validated International Index of Erectile Function
      (IIEF). MATERIALS AND METHODS: We performed a mail survey of male sexual function
      after deep dorsal vein arterialization in 68 consecutive literate men who
      underwent surgery between 1984 and 1998 for severe erectile dysfunction. The IIEF
      questionnaire and a questionnaire on patient characteristics were answered in a
      self-administered and nominative manner. Scores of the responders pertaining to
      the 5 domains of male sexuality were compared with those of the control groups
      used for the psychometric validation of the IIEF. RESULTS: Of the patients 38
      (55.9%) with a mean age plus or minus standard deviation of 46.5 +/- 11.9 years
      responded. Mean followup was 61.2 +/- 34.7 months. Compared to controls with
      erectile dysfunction controls men who underwent deep dorsal vein penile
      arterialization had significantly higher scores for erectile function, sexual
      desire, orgasmic function, intercourse satisfaction and overall satisfaction.
      Conversely compared with normal controls these patients reported significantly
      lower erectile function, orgasmic function, intercourse satisfaction and overall
      satisfaction scores, whereas sexual desire scores were similar in the 2 groups.
      No correlations were noted of the 5 IIEF domains with the duration of followup
      after arterialization. When erectile function scores were graded, 25.0% and 28.1%
      of patients reported no and or mild dysfunction, respectively, while 15.6% still
      complained of severe erectile dysfunction. CONCLUSIONS: Long-term improvement in
      the various aspects of male sexual function was observed after deep dorsal vein
      penile arterialization in a significant proportion of patients.

PMID- 11458072
TI  - Outpatient radical prostatectomy: impact of standard perineal approach on patient
      outcome.
AB  - PURPOSE: As managed care becomes more prevalent, urologists must critically
      evaluate the economic aspect of and patient satisfaction with urological practice
      patterns. We have previously reported the advantages of radical perineal
      prostatectomy, which decreases hospitalization and morbidity, and provides a more
      rapid return to normal activity, translating into cost savings. We have since
      evaluated the satisfaction of patients who underwent outpatient radical
      prostatectomy with and without laparoscopic pelvic lymph node dissection.
      MATERIALS AND METHODS: We evaluated the charts of 250 consecutive patients who
      underwent outpatient radical perineal prostatectomy with less than 24 hours of
      hospitalization from 1992 to 1997. Complications, pain management, blood
      transfusion, and bowel and urinary dysfunction were assessed. Validated quality
      of life questionnaires were mailed to 200 patients several months postoperatively
      and a 62% response rate was achieved. RESULTS: Mean followup in the series was 30
      months. In the perioperative period there were rectal perforation in less than 2%
      of patients, anastomotic stricture in 3%, perineal fistula in 0.4% and blood
      transfusion in 11%. Some problems with bowel movements immediately after the
      procedure, such as diarrhea, constipation or soiled underwear, developed in 17%
      of patients, of whom up to 20% had had some bowel dysfunction before surgery. In
      the majority bowel problems resolved in an average of 7.3 weeks. Persistent new
      onset bowel trouble developed in 9 of the 124 patients (7%). The questionnaire
      demonstrated persistent significant urinary incontinence in 8 cases (7%). Nerve
      sparing was attempted in 54 patients, including 22 (41%) who achieve erection
      sufficient for vaginal penetration and are satisfied with sexual function. Of the
      patients 17% reported problems after hospital discharge that were mostly related
      to Foley catheter management. Overall 94.8% of patients were satisfied with
      treatment. Physical and social/family well-being appeared to be excellent
      according to the questionnaire. Only 12% of patients would have preferred longer
      hospitalization. The preferred method of pain control was nonsteroidal anti
      inflammatory drugs. CONCLUSIONS: Radical perineal prostatectomy is a low
      morbidity alternative for localized prostate cancer. Outpatient radical perineal
      prostatectomy may be performed with good patient satisfaction and safety. There
      appear to be few bowel problems after long-term followup.

PMID- 11458073
TI  - Life after radical prostatectomy: a longitudinal study.
AB  - PURPOSE: We investigate the longitudinal recovery of quality of life after
      radical prostatectomy in men with localized prostate cancer. MATERIALS AND
      METHODS: We assessed the self-reported health related quality of life in 247 men
      undergoing radical prostatectomy for prostate cancer. Patients were assessed at
      baseline before surgery and postoperatively every 3 months for 1 year and then
      every 6 months for up to 48 months (median 30). We measured general and prostate
      specific health related quality of life with the RAND 36-Item Health Survey 1.0
      SF-36 and University of California, Los Angeles Prostate Cancer Index. The Cox
      proportional hazards regression model was used to determine whether some patients
      were more likely than others to have a successful return to baseline functioning
      after treatment. RESULTS: In the SF-36 60% of patients reached baseline in all
      domains by 3 months. By 12 months, greater than 90% of patients reached baseline
      in all domains. Mean recovery time for these domains was about 4(1/2) months. The
      recovery of urinary function to baseline was 21% at 3, 56% at 12 and 63% at 30
      months, respectively. About 80% of patients recovered to baseline urinary bother.
      In the urinary domains patients who recovered did so at an average of 7 to 8
      months, and there was little additional recovery after 18 months. By 1 year
      postoperatively, approximately a third of patients reached baseline sexual
      function and about half recovered to baseline sexual bother. At 2 years
      postoperatively, sexual function and bother returned to baseline in 40% and 60%
      of patients, respectively. Mean recovery time was about 11 months for sexual
      function and about 9 months for sexual bother. There was little additional
      recovery in the sexual domains after 18 to 24 months. In the bowel domains more
      than two thirds of patients returned to baseline by 3 months, and greater than
      90% recovered by 12 months, with a mean recovery of 4.8 months. Unmarried men
      were more likely than those married to regain baseline sexual function (p = 0.03)
      and urinary function (p = 0.07). Patients who were 65 years and older were more
      likely than those younger to return to baseline sexual bother (p = 0.03). There
      were trends that showed patients with higher incomes as well as those who were
      white were more likely to recover baseline scores for urinary function and the
      physical component summary. Another trend suggested that men with a higher
      education were less likely to regain urinary function (p = 0.08). CONCLUSIONS:
      Most quality of life recovery occurs early after radical prostatectomy, except in
      several domains, including urinary and sexual, which continue to improve even
      beyond 2 years postoperatively. Patients should be encouraged that recovery may
      continue for months or years after surgery.

PMID- 11458074
TI  - Missed anterior crossing vessels during open retroperitoneal pyeloplasty:
      laparoscopic transperitoneal discovery and repair.
AB  - PURPOSE: Extrinsic ureteropelvic junction obstruction due to anterior crossing
      segmental renal vessels is present in more than 50% of patients in adulthood. In
      this situation the ureter must usually be dismembered and transposed anterior to
      the crossing vascular structures, where it is anastomosed to the renal pelvis.
      Via the open retroperitoneal approach there may be a limited view of the anterior
      surface of the ureteropelvic junction and, hence, anterior crossing vessels may
      possibly be missed. We describe 2 patients with ureteropelvic junction
      obstruction in whom anterior vessels were missed during open retroperitoneal
      repair. Laparoscopic transperitoneal secondary pyeloplasty with posterior
      displacement of the crossing renal vessel was performed in each case. MATERIALS
      AND METHODS: Two patients presented with symptomatic congenital ureteropelvic
      junction obstruction after failed endopyelotomy in 1 and failed open
      retroperitoneal procedures in both. Preoperatively spiral computerized tomography
      angiography with a ureteropelvic junction protocol revealed crossing vessels in
      the 2 cases. This finding was confirmed at transperitoneal laparoscopic
      pyeloplasty. The ureter and renal pelvis were transposed anterior to the crossing
      vessels and 2 rows of running sutures were placed to complete the anastomosis.
      RESULTS: The 2 laparoscopic procedures were completed successfully. The anterior
      crossing vessels were preserved in each case. Currently the patients are
      asymptomatic and furosemide washout renal scan was normal. CONCLUSIONS: Spiral CT
      angiography reliably delineates the renal vascular anatomy in patients with
      ureteropelvic junction obstruction. This study may be valuable before planned
      open retroperitoneal ureteropelvic junction obstruction repair. Laparoscopic
      pyeloplasty may successfully manage anterior crossing vessels associated with
      secondary ureteropelvic junction obstruction.

PMID- 11458075
TI  - Complete phalloplasty using the free radial forearm flap for correcting
      micropenis associated with vesical exstrophy.
AB  - PURPOSE: We present a new surgical technique for reconstructing the penis in a
      man with micropenis associated with vesical exstrophy. MATERIALS AND METHODS: A
      free radial forearm flap was used to create a penis of normal length and
      diameter. The flap was wrapped around the native micropenis. A penile prosthesis
      was then inserted in the flap to provide erection. RESULTS: The flap was well
      vascularized and no skin damage was observed 6 years after reconstruction. The
      patient achieved sexual intercourse on a regular basis. He is satisfied with the
      result. CONCLUSIONS: Free transfer of the radial forearm flap may be done in
      select men with micropenis associated with vesical exstrophy for penile
      reconstruction. An inflatable prosthesis may be inserted in the flap to provide
      erection. The results of this technique have remained stable in the long term.
      This method provides a new tool for phalloplasty in these difficult cases.

PMID- 11458076
TI  - Laparoscopic diagnosis and management of acute intra-abdominal testicular
      torsion.

PMID- 11458077
TI  - Solitary fibrous tumor of the kidney.

PMID- 11458078
TI  - Norepinephrine producing renal cell carcinoma.

PMID- 11458079
TI  - Urachal carcinoma associated with increased carbohydrate antigen 19-9 and
      carcinoembryonic antigen.

PMID- 11458080
TI  - Synovial sarcoma metastatic to the penis and prostate.

PMID- 11458081
TI  - Paratesticular spindle cell rhabdomyosarcoma in an adult.

PMID- 11458082
TI  - The natural progression of adenocarcinoma of the epididymis.

PMID- 11458083
TI  - Extragonadal germ cell tumor of the prostate.

PMID- 11458084
TI  - Response of hormone refractory prostate cancer to lycopene.

PMID- 11458085
TI  - Malignant mesothelioma of the pelvis.

PMID- 11458086
TI  - Retrovesical hematoma secondary to clean intermittent self-catheterization.

PMID- 11458087
TI  - Migration of a prosthetic acetabulum into the bladder.

PMID- 11458088
TI  - Penile incarceration with barbell retaining ring.

PMID- 11458089
TI  - Traumatic avulsion of the dorsal penile artery mimicking a penile fracture.

PMID- 11458090
TI  - The use of a rectus muscle flap in the repair of a prostato-rectal fistula.

PMID- 11458091
TI  - Retroperitoneal fibrosis: a rare complication of Pott's disease.

PMID- 11458092
TI  - Polyarteritis nodosa presenting as hematuria and a testicular mass.

PMID- 11458093
TI  - Emphysematous prostatic abscess after transurethral microwave thermotherapy.

PMID- 11458094
TI  - Urethral diverticulum following transurethral collagen injection.

PMID- 11458095
TI  - Effects of ejaculation by penile vibratory stimulation on bladder reflex activity
      in a spinal cord injured man.

PMID- 11458096
TI  - Successful treatment of recalcitrant priapism using intercorporeal injection of
      tissue plasminogen activator.

PMID- 11458097
TI  - Re: Laparoscopic retroperitoneal live donor right nephrectomy for purposes of
      allotransplantation and autotransplantation.

PMID- 11458098
TI  - Re: Lessons learned from laser tissue soldering and fibrin glue pyeloplasty in an
      in vivo porcine model.

PMID- 11458099
TI  - Re: Port site tumor recurrences of renal cell carcinoma after videolaparoscopic
      radical nephrectomy.

PMID- 11458100
TI  - Re: Outcome of patients with grossly node positive bladder cancer after pelvic
      lymph node dissection and radical cystectomy.

PMID- 11458101
TI  - Re: Malignant germ cell tumor of the contralateral testis after radiotherapy for
      testicular intraepithelial neoplasia.

PMID- 11458102
TI  - Re: Neoadjuvant hormonal ablative therapy before radical prostatectomy: a review.
      Is it indicated?

PMID- 11458103
TI  - Re: Medical versus surgical androgen suppression therapy for prostate cancer: a
      10-year longitudinal cost study.

PMID- 11458104
TI  - Re: Nonoperative treatment of patients with presumed penile fracture.

PMID- 11458105
TI  - Re: Effect of the depth and width of the urethral plate on tubularized incised
      plate urethroplasty.

PMID- 11458106
TI  - Re: standardized ultrasound method for assessing detrusor muscle thickness in
      children.

PMID- 11458107
TI  - Re: Factors predicting recovery of erections after radical prostatectomy.

PMID- 11458108
TI  - Small intestinal submucosa as a urethral coverage layer.
AB  - PURPOSE: Urethrocutaneous fistula is the most common complication of hypospadias
      surgery. Numerous techniques have been used to decrease the incidence of this
      complication and the use of biocompatible materials in surgery has expanded the
      options in difficult situations. We hypothesized that porcine small intestinal
      submucosa may be used as a coverage layer after urethral surgery. We evaluated
      the histological changes associated with small intestinal submucosa when used as
      a coverage layer over the urethra in a rabbit model. METHODS AND METHODS: We
      performed urethral surgery in 16 New Zealand White rabbits divided into 4 animals
      each in groups 1-sham operation with penile degloving only, 2-penile degloving
      and small intestinal submucosa patch placement, 3-urethrotomy without a patch and
      4-urethrotomy with a small intestinal submucosa patch. The graft edges were
      marked with permanent suture at surgery for later identification. All rabbits
      were maintained for 6 weeks before sacrifice. The urethra of each animal was then
      serially sectioned and examined histologically. RESULTS: Histological examination
      of animals with an small intestinal submucosa patch revealed a foreign body
      tissue reaction with an infiltrate of histiocytes, giant cells and lymphocytes in
      the area of graft placement. There was no histological evidence of remaining
      small intestinal submucosa patch in any sections. The urethral mucosa healed
      normally in all cases in which it was disrupted. There was no evidence of acute
      or chronic inflammation in any group 1 or 2 nonsmall intestinal submucosa animals
      and none in the animals with a small intestinal submucosa graft in areas other
      than the former graft site. There were also no urethrocutaneous fistulas in any
      of the 8 rabbits that underwent urethrotomy. CONCLUSIONS: Small intestine
      submucosa provides an adequate coverage layer in the rabbit penis after
      urethrotomy. Histologically the foreign material did not alter normal healing of
      the urethral mucosa, although it did appear to cause an infiltration of
      histiocytes, giant cells and lymphocytes. Small intestinal submucosa has
      previously been studied as a scaffold on which tissue may be remodeled or may
      regenerate. Our study shows that small intestinal submucosa did not interfere
      with normal tissue healing in this animal model. When used as a urethral coverage
      layer, it appears to provide extra tissue between the urethra and skin. Small
      intestinal submucosa may potentially decrease the incidence of urethrocutaneous
      fistula after urethral surgery.

PMID- 11458109
TI  - Construction of female urethra using buccal mucosa graft.
AB  - PURPOSE: We reviewed our experience with buccal mucosa grafts for reconstructing
      difficult female urethral problems. METHODS AND METHODS: Since 1994, we have used
      a buccal mucosa graft to reconstruct the urethra in 7 girls 3 to 13 years old.
      The underlying pathological condition was a fibrotic urethra after previous
      operations for cloacal exstrophy, cloacal malformation, iatrogenic urethral
      stricture, and multiple false passages in a previously reconstructed urethra of
      vaginal mucosa that made clean intermittent catheterization difficult. A full
      thickness buccal mucosa graft was tubularized in situ as the neourethra to the
      base of the clitoris. In patients with cloacal exstrophy and cloacal malformation
      the bladder neck and urethra were widely exposed transabdominally by splitting
      the pubic symphysis. The fibrotic mucosa was excised and the tubularized buccal
      mucosa graft was wrapped with periurethral tissues. Other patients underwent
      transvaginal surgery in the prone position and the graft was covered with a
      buttock flap. RESULTS: Patients were followed for 12 to 58 months (mean 34.7).
      Those with cloacal exstrophy and cloacal malformation had been completely
      incontinent before urethral reconstruction but all attained complete continence
      postoperatively. They and the girl who underwent urethral reconstruction for
      difficult catheterization performed clean intermittent catheterization easily.
      The patient with urethral stricture voided via the urethra without difficulty.
      CONCLUSIONS: In select female patients with difficult urethral reconstructive
      problems a tubularized free graft obtained from the buccal mucosa may be
      effectively used when local tissue is fibrotic and unsuitable for creating a
      supple new urethra.

PMID- 11458110
TI  - Transverse retubularized sigmoidovesicostomy continent urinary diversion to the
      umbilicus.
AB  - PURPOSE: The most widely used conduit when creating continent urinary diversion
      based on the Mitrofanoff principle has been appendicovesicostomy. However,
      appendix is not always available and it is increasingly used for the antegrade
      continence enema in situ appendix procedure. In 1993 the technique of transverse
      retubularization of the ileum to create a continent catheterizable conduit for an
      ileal reservoir was described and in 1997 this technique was studied in an animal
      model. Larger patients may need 2 ileal segments in series to bridge the distance
      between the umbilicus and bladder. To avoid using 2 segments we used transverse
      retubularized sigmoid colon to create a catheterizable sigmoidovesicostomy to the
      umbilicus. METHODS AND METHODS: In 5 children 6 to 19 years old (mean age 15)
      with neurogenic bladder secondary to spina bifida a transverse retubularized
      sigmoidovesicostomy to the umbilicus was performed. In all patients an antegrade
      continence enema procedure was done for refractory constipation and overflow
      fecal incontinence secondary to neurogenic bowel. Laparoscopy was performed to
      mobilize the appendix in patients who requested a low Pfannenstiel incision for
      better cosmesis. Additional procedures included the pubovaginal sling placement
      and sigmoid colocystoplasty. RESULTS: Mean length of the sigmoidovesicostomy,
      which was equal to the circumference of the sigmoid before retubularization, was
      13 cm. (range 10 to 15). This sigmoid conduit reached the umbilicus easily in all
      cases. All sigmoidovesicostomies were easily catheterized and all were continent.
      One patient with morbid obesity (body mass index 40.4) had a mucocutaneous
      anastomotic breakdown 3 months postoperatively. Minimum followup was 1 year (mean
      1.5). CONCLUSIONS: Transverse retubularized sigmoidovesicostomy is effective for
      creating a continent urinary diversion to the umbilicus in patients with
      neurogenic bladder secondary to spina bifida. Dilating the sigmoid colon from
      neurogenic bowel creates a long conduit based on the Yang-Monti principle and 2
      ileal segments with an anastomosis are not required. Additional benefits are that
      the sigmoid colon is readily accessible via a low Pfannenstiel incision and may
      also be used for augmentation in select cases.

PMID- 11458111
TI  - Reflux nephropathy in infancy: a comparison of infants presenting with and
      without urinary tract infection.
AB  - PURPOSE: We compared the incidence of renal scarring in infants with high grade
      vesicoureteral reflux in those presenting with and without urinary tract
      infection. METHODS AND METHODS: We reviewed the medical records of 81 male and 46
      female infants (194 renal refluxing units) with a mean age of 4 months who had
      grade IV or V primary vesicoureteral reflux and underwent an anti-reflux
      procedure between 1984 and 1997. Dimercapto-succinic acid (DMSA) scans and
      voiding cystourethrography were performed in all cases. Patients were followed
      for 2 to 16 years, including 90% for greater than 3 years. Renal ultrasound and
      DMSA scan were done at followup. RESULTS: A total of 97 patients (76%) (148
      refluxing renal units) presented clinically with urinary tract infection. The
      initial DMSA scan demonstrated renal scarring in 40 of the 106 grade IV (38%) and
      28 of the 42 grade V (67%) refluxing renal units. There was no scarring on
      followup in previously normal refluxing renal units. Of the patients 30 (24%) (46
      refluxing renal units) were diagnosed before a urinary tract infection developed,
      16 underwent screening due to vesicoureteral reflux in a sibling and in 10 reflux
      was initially suspected due to hydronephrosis on prenatal ultrasound. In the
      remaining 4 patients vesicoureteral reflux was suspected during abdominal
      ultrasound to investigate abdominal pain, jaundice, associated hypospadias and
      fetal alcohol syndrome, respectively. DMSA scan showed evidence of scarring in 6
      of 21 grade IV (29%) and 9 of 25 grade V (36%) refluxing renal units in this
      group. Followup revealed scarring in only 1 previously normal refluxing renal
      unit. CONCLUSIONS: The incidence of reflux nephropathy in primary grade V
      vesicoureteral reflux is lower in cases detected by screening and with treatment
      it remained lower than in cases of urinary tract infection that presented
      clinically. Early treatment of grade V vesicoureteral reflux made possible by
      screening may prevent renal damage.

PMID- 11458112
TI  - The decompensated detrusor V: molecular correlates of bladder function after
      reversal of experimental outlet obstruction.
AB  - PURPOSE: Calcium ion homeostasis has a significant role in smooth muscle
      function. Its regulation requires complex storage and release mechanisms via ion
      pumps and channels located within intracellular storage sites (sarcoplasmic
      reticulum) and at the plasma membrane. We have previously reported a dramatic
      loss of the 2 major sarcoplasmic reticulum proteins sarcoplasmic endoplasmic
      reticulum calcium magnesium adenosine triphosphatase (SERCA2) and the ryanodine
      sensitive ion channel, also called the ryanodine receptor, after outlet
      obstruction. In our current study we investigated the correlation of the
      expression of these 2 major sarcoplasmic reticulum components with bladder
      function recovery after the reversal of outlet obstruction. METHODS AND METHODS:
      Standard partial bladder outlet obstruction was created in adult New Zealand
      White rabbits. Voiding patterns were monitored 2 and 4 weeks postoperatively, and
      rabbits were selected for outlet obstruction reversal based on a voiding pattern
      consistent with a decompensated state, as indicated by a frequency of greater
      than 30 voids daily and an average voided volume of less than 4 cc. Bladder
      biopsy was done when outlet obstruction was reversed. Voiding performance was
      monitored postoperatively and the animals were sacrificed 2 weeks later. Voiding
      patterns and muscle strip studies enabled us to define 2 functional outcome
      categories after reversal, namely normal versus minimally improved. Microsomal
      membrane protein fractions were prepared from the same bladder tissues before and
      after reversal, and probed by Western blot analysis for SERCA2 and ryanodine
      receptor expression. RESULTS: Western blot analysis revealed a major loss of
      SERCA2 and ryanodine receptor expression at the time of reversal and biopsy. In
      65% of bladders obstruction reversal resulted in a normalized voiding pattern
      with a recovery of ryanodine receptor expression that was 15% to 65% of control
      values. In contrast, in the 35% of bladders with persistent voiding symptoms
      there was minimal recovery of ryanodine receptor expression. SERCA2 expression
      increased slightly in each group after reversal but did not differ in bladders
      with normalized versus improved function. CONCLUSIONS: Bladder decompensation is
      highly associated with a loss of sarcoplasmic reticulum function. Furthermore,
      the decompensated detrusor recovers function after obstruction reversal, which is
      associated with the recovery of these sarcoplasmic reticulum components.

PMID- 11458113
TI  - Rectus fascial sling for the treatment of neurogenic sphincteric incontinence in
      boys: is it safe and effective?
AB  - PURPOSE: While a fascial sling for treating children with intractable urinary
      incontinence is often successful in girls, its effectiveness in boys remains
      unclear. We determined the long-term efficacy of a rectus fascial sling in boys
      with neurogenic sphincteric incontinence and defined its urodynamic
      characteristics for achieving continence. METHODS AND METHODS: We reviewed the
      charts of all boys who underwent a rectus fascial sling procedure for neurogenic
      incontinence to determine urinary continence status at the most recent office
      visit or by telephone interview, the type and dose of anticholinergic and
      sympathomimetic medications, the frequency of intermittent clean intermittent
      catheterization, status of the upper urinary tract and comparative urodynamic
      findings preoperatively and postoperatively. RESULTS: We evaluated 7 boys 7 to 19
      years old, of whom 4 were postpubertal, who fulfilled study criteria and had a
      followup of 1 to 9 years. In 4 patients a continent stoma was created
      concurrently at surgery. Postoperatively all patients were dry during the first 3
      months after surgery. At the last followup 1 patient was completely dry, 3 had
      occasional nighttime wetting, 2 had occasional stress incontinence, and 1 had
      frequent daytime and nighttime wetting requiring subsequent bladder neck closure.
      Prepubertal and postpubertal males performed catheterization without difficulty
      and all required less frequent clean intermittent catheterization and medication
      postoperatively compared to preoperative status. None had hydronephrosis.
      Postoperatively urodynamic evaluation revealed normal bladder compliance,
      improved urethral resistance that did not decay with bladder filling and no
      uninhibited contractions. CONCLUSIONS: The rectus fascial sling is effective for
      increasing bladder outlet resistance and decreasing the degree of incontinence in
      prepubertal and postpubertal males with neurogenic sphincteric incontinence. It
      has no long-term deleterious effects on bladder function and does not impair the
      ability to catheterize postoperatively. A fascial sling is an effective
      alternative to bladder neck closure when creating a continent stoma.

PMID- 11458114
TI  - Telomerase in urological malignancy.
AB  - PURPOSE: Telomerase is a ribonucleoprotein enzyme that compensates for the
      progressive erosion of chromosomal ends, called telomeres. In most somatic cells
      telomerase expression is repressed and telomeres progressively shorten after each
      cell division, causing cell senescence. Conversely telomerase is active in most
      human cancers, maintaining the integrity of chromosome ends and representing an
      important step in cell immortalization and carcinogenesis. The large and
      increasing interest in telomerase was motivated by the demonstration that more
      than 90% of human cancers are telomerase positive, whereas most normal tissues or
      benign tumors contained low or undetectable telomerase activity. We addressed the
      most recent data on telomerase detection in urological malignancy. Approaches to
      telomerase inhibition as a future anti-cancer therapy are also discussed.
      MATERIALS AND METHODS: We comprehensively reviewed the most recent and
      significant publications in this field using current issues of specific journals
      and a MEDLINE search. RESULTS: Telomerase is often expressed in bladder (90%),
      prostate (80%) and renal (69%) carcinoma. A variable but significant percent of
      normal tissues from tumor adjacent zones or noncancer samples are positive for
      telomerase. The clinical role of telomerase is still questionable in renal
      cancer, while important insights into the diagnostic role of telomerase in
      bladder and prostate carcinoma are increasing. Telomerase detection in exfoliated
      cells collected with urine or bladder washings seems a promising tool for the
      diagnosis and management of bladder cancer. CONCLUSIONS: Larger perspective
      studies of larger groups of patients are required to discover an appropriate role
      for telomerase when assessing these tumors. The improvement of quantitative
      methods to evaluate the expression of telomerase is a cornerstone in the complete
      clarification of the clinical relevance of telomerase.

PMID- 11458115
TI  - Co-localization of androgen receptor with estrogen receptor beta in the lower
      urinary tract of the male rat.
AB  - PURPOSE: Androgens and estrogens influence voiding. In this study their target
      sites in the lower urinary tract of the male rat were identified. MATERIALS AND
      METHODS: Cryosections of the bladder body, bladder neck, prostatic urethra, mid
      proximal urethra and prostatic autonomic ganglia of adult male rats were
      immunostained with specific estrogen receptor alpha, estrogen receptor beta
      (ERbeta) or androgen receptor (AR) antibodies. The sections were then examined
      under conventional, fluorescence or confocal fluorescence microscopy. RESULTS: Co
      expression of AR and ERbeta in the urothelium, bladder smooth muscle cells,
      proximal urethra striated muscle cells and neurons in the autonomic ganglia of
      the prostatic plexus suggests that estrogen and androgen have direct effects in
      the lower urinary tract. CONCLUSIONS: The local interaction of AR and ERbeta in
      the hormonal control of voiding is an intriguing possibility.

PMID- 11458116
TI  - Regulation of keratinocyte growth factor receptor and androgen receptor in
      epithelial cells of the human prostate.
AB  - PURPOSE: Stromal-epithelial interactions of growth factors and the androgen
      receptor may have implications for the pathophysiology of benign and neoplastic
      transformation of the human adult prostate. We investigated a possible
      interaction of keratinocyte growth factor with its receptor as well as with the
      androgen receptor signaling pathway in human prostatic epithelial cells.
      MATERIALS AND METHODS: Human prostatic epithelial cells were obtained from
      explant primary culture, established in DU145 cell conditioned medium and
      maintained in keratinocyte serum-free medium with supplements. Epithelial cells
      were characterized by light and electron microscopy, and immunocytochemical study
      using epithelial and mesenchymal markers. Androgen receptor, keratinocyte growth
      factor receptor and keratinocyte growth factor messenger RNA expression was
      measured by polymerase chain reaction (PCR). The response to 0.01 to 10 nM.
      dihydrotestosterone, 10 microM. flutamide and 1 to 1,000 ng./ml. keratinocyte
      growth factor was tested by [3H] thymidine assay. The difference in keratinocyte
      growth factor receptor and androgen receptor gene expression after treatment with
      and without keratinocyte growth factor and flutamide were determined by
      quantitative multiplex PCR and quantitated using densitometry analysis. RESULTS:
      Immunocytochemical and electron microscopy characterization revealed typical
      epithelial differentiation. PCR showed keratinocyte growth factor receptor and
      androgen receptor expression in epithelial cultured cells but no keratinocyte
      growth factor expression. Epithelial cells showed a significant time and dose
      dependent stimulation of cell proliferation with keratinocyte growth factor and
      dihydrotestosterone (p <0.05). When combined with the anti-androgen flutamide the
      effect of 100 ng./ml. keratinocyte growth factor was significantly decreased (p
      <0.05). At 100 ng./ml. keratinocyte growth factor quantitative multiplex PCR
      revealed stimulated keratinocyte growth factor receptor and androgen receptor
      messenger RNA expression. CONCLUSIONS: These results show that keratinocyte
      growth factor up-regulates the keratinocyte growth factor and androgen receptors
      in the absence of androgen. Thus, the androgen signaling pathway may be activated
      by growth factors such as keratinocyte growth factor in an androgen deficient
      environment.

PMID- 11458117
TI  - Gastric patch pyeloplasty: development of an animal model to produce upper tract
      urinary acidification for treating struvite urinary calculi.
AB  - PURPOSE: Struvite calculi form in an alkaline environment created by urease
      producing uropathogens. We developed a viable upper tract urinary acidification
      model by performing gastric patch pyeloplasty in the rabbit. This model produces
      urinary acidification sufficient for the treatment and prevention of struvite
      renal calculi. We evaluated the physiological, metabolic and surgical outcomes.
      MATERIALS AND METHODS: gastric segment was harvested based on branches of the
      left gastro-epiploic artery. The flap was folded along the transverse axis and
      the adjacent edges were closed. The mouth of this reconfigured pouch provided
      optimal dimensions for anastomosis with the diminutive renal pelvis. Half of the
      rabbits were treated with internal stenting and H-2 blockade. Urinary pH was
      assessed by weekly cage collection and direct collection from the cannulated
      ureters. Urine culture was done, and serum gastrin and electrolytes were assessed
      at regular intervals. The rabbits were sacrificed at 3 to 26 weeks. Histological
      examination was routinely performed. RESULTS: A total of 15 rabbits were
      available for complete assessment. Sustained urinary acidification was produced
      in 7 animals (47%) with a mean pH decrease of 2.27. In another 2 rabbits (13%)
      the urine was initially acidic but subsequently became alkaline due to ureteral
      obstruction. Electrolytes and gastrin were unchanged in these rabbits and urine
      culture was positive in 2. Histological testing revealed nonspecific inflammatory
      changes of the renal pelvis. Anastomotic complications were the most common
      surgical complication and the most common cause of failed acidification. The
      cohort treated without stents and H-2 blockade was at significantly greater risk
      for anastomotic leakage. CONCLUSIONS: Gastric patch pyeloplasty may significantly
      increase urinary acidity in the rabbit model without altering the serum
      electrolyte balance or gastrin level. The procedure utilizes common techniques of
      reconstructive urology and may be possible with laparoscopy. Further study is
      required to assess the in vivo effect of this procedure for treating and
      preventing upper tract struvite calculi.

PMID- 11458118
TI  - Solid phase assay of urine cystine supersaturation in the presence of cystine
      binding drugs.
AB  - PURPOSE: We report a new kind of assay system for urine cystine supersaturation
      that is accurate in the presence of cystine binding thiol drugs. We measured the
      molar ratio of cystine dissolved per mole of drug. MATERIALS AND METHODS:
      Measured amounts of cystine crystals were incubated in buffer or urine for 48
      hours with stirring. The solid phase remaining was pelleted by centrifugation,
      extracted into a high pH buffer and measured. D-penicillamine, tiopronin and
      captopril were added to determine their effect on solid phase dissolution.
      RESULTS: Total cystine calculated from urine and solid measurements closely
      matched the amounts of cystine weighed in, meaning that the assay system
      successfully recovered the total cystine from the 2 phases. Each drug dissolved
      solid cystine in a specific and fixed proportion to its molar concentration in
      the range of 0.2 to 0.4 mM. dissolution per mM. of drug. Solution measurements
      were not a reliable gauge to the actual amounts of cystine dissolved.
      CONCLUSIONS: Changes in solid phase cystine accurately reflect buffer or urine
      supersaturation when thiol drugs are present. The solid phase assay is a
      technically straightforward and reliable way of assessing cystine movement into
      and out of urine that avoids complexity of measurement and distortions of assay
      systems by drugs. This assay enables one to assess the level of drug effect and
      the need for a change in dosing.

PMID- 11458119
TI  - Inhibition of telomerase is related to the life span and tumorigenicity of human
      prostate cancer cells.
AB  - PURPOSE: Telomerase, the enzyme that catalyzes the elongation of telomeres, is
      illegitimately activated in the majority of cancers, including that of the
      prostate, where it may greatly extend the life span of malignant cells. The
      inhibition of telomerase by molecular intervention has been shown to lead
      eventually to cell death in several tumor or in vitro immortalized cell lines and
      in 1 case prevent tumor growth in vivo. Therefore, we tested whether a similar
      strategy may be used to limit the tumorigenic potential of late stage prostate
      cancer cells. MATERIALS AND METHODS: PC-3, LNCaP and DU-145 human prostate cancer
      cells were infected with a retrovirus encoding a dominant-negative version of the
      catalytic subunit of telomerase (DN-hTERT). Subclones or polyclonal populations
      were assayed for DN-hTERT expression, telomerase activity, telomere length, cell
      life span and in most cases tumorigenicity in nude mice. RESULTS: DN-hTERT
      expression levels directly correlated with cell life span and tumorigenic growth.
      PC-3 cells expressing high levels of DN-hTERT died rapidly and failed to form
      tumors in nude mice, whereas cells expressing the lowest levels proliferated the
      longest and generated tumors that later spontaneously regressed. Similarly the
      inhibition of telomerase activity in LNCaP cells was greater than in DU-145 cells
      and correspondingly LNCaP cells had a shorter life span. CONCLUSIONS: DN-hTERT
      expression limits the life span and tumorigenic potential of human prostate
      cancer cells, although the onset of these effects appears to be dictated by the
      expression level of DN-hTERT. Therefore, telomerase represents an attractive
      target for potentially managing prostate cancer. Nevertheless, effective means of
      inhibiting the enzyme may be required for a therapeutically useful outcome.

PMID- 11458120
TI  - Disseminated cytokeratin positive tumor cells in the bone marrow of patients with
      prostate cancer: detection and prognostic value.
AB  - PURPOSE: Previous investigations have shown that cytokeratin 18 positive bone
      marrow cells in localized and lymphatically spread prostate cancer correlates
      with neither established prognostic factors nor with the biochemical and clinical
      course after radical prostatectomy. Since the well-known down-regulation of
      cytokeratin 18 in tumor cells may lead to false-negative results, we asked
      whether staining with a pan-cytokeratin antibody recognizing a common epitope of
      cytokeratins 8, 18 and 19 would result in different data. MATERIALS AND METHODS:
      Preoperative bone marrow aspirates of 82 patients with localized (N0) and
      lymphatically spread (N1) prostate cancer were examined using the monoclonal
      antibody cytokeratin 2 and the pan-cytokeratin antibody A 45-B/B3, called A 45.
      RESULTS: In contrast to findings with the cytokeratin 18 antibody, those with the
      pan-cytokeratin antibody correlated with the biochemical course. At a median
      followup of 1,477 days (4 years) patients with pan-cytokeratin positive cells in
      the preoperative bone marrow aspirate had biochemical progression significantly
      earlier than those with pan-cytokeratin negative results (mean time to prostate
      specific antigen relapse 886 versus 1,409 days, p < or =0.004). Compared with
      other parameters, such as prostate specific antigen, pathological stage and
      Gleason score, preoperative pan-cytokeratin findings proved to be an independent
      prognostic factor. CONCLUSIONS: Cytokeratin positive cells in the bone marrow
      also have prognostic relevance in prostate cancer. The comprehensive analysis of
      these cells, studies of the individual course of these findings and sufficiently
      long followup allow us to discuss whether and under what conditions metastasis
      may develop from 1 or several cytokeratin positive cells.

PMID- 11458121
TI  - Methylation of the E-cadherin gene promoter correlates with progression of
      prostate cancer.
AB  - PURPOSE: We studied the methylation status of E-cadherin gene promoter in
      prostate cancer and its relationship with E-cadherin inactivation in prostate
      cancer. MATERIALS AND METHODS: Seven human prostate cell lines and 35
      microdissected prostate cancer specimens were analyzed for E-cadherin promoter
      methylation using the bisulfite genome sequencing technique. E-cadherin messenger
      (m)RNA expression and protein expression were also studied in prostate cell lines
      by reverse transcriptase-polymerase chain reaction and in prostate cancer
      specimens by immunostaining, respectively. RESULTS: The overall methylation of E
      cadherin promoter was evident in 14 of 20 grades III to V (70%) and in 5 of 15
      grades I to II (33%) prostate cancer samples. It correlated with absent or
      reduced E-cadherin immunostaining. Methylation in low grade tumors was present
      mainly in the exon region, whereas in high grade tumors methylation was also
      present in the promoter region. Methylation was noted in 2 of 6 prostate cancer
      cell lines (33%) and correlated well with decreased E-cadherin mRNA in these cell
      lines. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored E
      cadherin mRNA levels in the E-cadherin negative prostate cancer cell lines TSUPr1
      and DuPro. CONCLUSIONS: Methylation of the E-cadherin gene is common in prostate
      cancer and the severity of E-cadherin methylation correlates with tumor
      progression. This study implies that the invasion and metastasis suppressor
      function of E-cadherin may often be compromised in human prostate cancer by
      epigenetic rather than by mutational events.

PMID- 11458122
TI  - Effects of sodium hyaluronate on epithelial healing of the vesical mucosa and
      vesical fibrosis in rabbits with acetic acid induced cystitis.
AB  - PURPOSE: To evaluate the effect of sodium hyaluronate on epithelial healing of
      the vesical mucosa and vesical fibrosis, and clarify the effect of the sodium
      hyaluronate solution concentration, we administered sodium hyaluronate in the
      bladder of rabbits with acetic acid induced cystitis. MATERIALS AND METHODS:
      Sodium hyaluronate at 3 concentrations (0.1%, 0.2% and 0.4%) was injected
      intravesically into rabbits with cystitis. Seven days after injection the effect
      of sodium hyaluronate was evaluated by bladder capacity measurement. Furthermore,
      the epithelial defective region of the mucosal membrane and bladder dry weight
      were determined and the condition of the epithelial membrane and extent of
      fibrosis were examined histologically. RESULTS: In all sodium hyaluronate treated
      groups a significant improvement in bladder capacity was observed compared to
      controls. In addition, a significant reduction was noted in the area of the
      epithelial defective region in the groups treated with 0.2% or 0.4% sodium
      hyaluronate and a significant decrease was noted in bladder dry weight in the
      group treated with 0.4% sodium hyaluronate. Histological examination revealed
      accelerated epithelial healing of the vesical mucosa and inhibited vesical
      fibrosis in the group treated with 0.4% sodium hyaluronate. CONCLUSIONS: Our
      findings suggest that sodium hyaluronate is effective for promoting epithelial
      healing of the vesical mucosa and inhibiting vesical fibrosis.

PMID- 11458123
TI  - Systemic and topical drug administration in the pig ureter: effect of
      phosphodiesterase inhibitors alpha1, beta and beta2-adrenergic receptor agonists
      and antagonists on the frequency and amplitude of ureteral contractions.
AB  - PURPOSE: We searched for compounds that are pharmacologically active on ureteral
      motility for treating ureteral colic to ease retrograde access into the ureter
      and improve the clearance of stones or stone particles from the ureter. The
      effects of the alpha1-adrenergic receptor agonist phenylephrine, the nonselective
      beta and beta2-adrenergic receptor agonists isoproterenol and fenoterol, and the
      phosphodiesterase inhibitors papaverine (nonspecific) and rolipram (type IV) on
      the frequency and amplitude of ureteral contractions when administered
      intravenously or topically were investigated in pigs. MATERIALS AND METHODS: A
      total of 52 pigs were anesthetized. A double lumen 6Fr catheter was inserted
      through each renal pelvis and into the ureter, allowing perfusion of saline or
      drug solution into the renal pelvis and the recording of contractions from the
      mid portion of the ureter. RESULTS: The alpha1 and beta-adrenergic receptors of
      the ureter are not tonically activated by endogenous epinephrine or
      norepinephrine. Phenylephrine administered intravenously at a dose of 0.01 to 3
      mg./kg. and topically at 0.1 to 3 mg./ml. per minute increased contraction
      frequency 10 and 4-fold, respectively, and contraction amplitude 2-fold each in a
      dose dependent manner. Arterial blood pressure increased markedly during
      intravenous administration of phenylephrine but was minimally affected during
      topical application. The phenylephrine effects were reversed by the antagonist
      prazosin. Isoproterenol administered intravenously at a dose of 0.01 to 10
      mg./kg. and topically at 0.1 to 200 microg./ml. per minute decreased contraction
      frequency to 13% and 31% of controls, respectively. Contraction amplitude was not
      affected by intravenous administration but decreased to 59% of controls when
      applied topically. These effects were also observed with a slight delay in the
      saline perfused contralateral ureter. The heart rate also increased, suggesting
      absorption of the drug by the urothelium. The isoproterenol effects were blocked
      by the antagonist propranolol. Fenoterol administered intravenously at a dose of
      0.1 to 30 microg./kg. and topically at 0.003 to 1 mg./ml. per minute decreased
      contraction frequency to 14% and 10% of controls, and contraction amplitude to
      84% and 65%, respectively. These effects on the drug perfused ureter were also
      observed on the contralateral saline perfused ureter but to a lesser extent. The
      fenoterol effects were blocked by the antagonist propranolol. Papaverine
      administered intravenously at a dose of 0.001 to 3 mg./kg. decreased contraction
      frequency to 33% of controls. Topically administered papaverine as well as
      intravenous and topically administered rolipram had no relevant effect on
      ureteral motility. CONCLUSIONS: Intravenous phenylephrine increases, and
      isoproterenol and fenoterol decrease the frequency and amplitude of ureteral
      contractions in the pig. The same effects are observed with the topical
      administration of phenylephrine, which causes a significant local but not
      systemic side effect. Topical administration of isoproterenol and fenoterol
      produced local as well as systemic effects, suggesting absorption by the
      urothelium. However, to our knowledge a drug that relaxes ureteral peristalsis in
      pigs without causing systemic side effects has not yet been identified.

PMID- 11458124
TI  - Aging effects on contractility of longitudinal and circular detrusor and trigone
      of rat bladder.
AB  - PURPOSE: Aging is associated with bladder dysfunction, including difficult
      voiding and urinary leakage. Voiding involves reduction in the bladder lumen in
      all dimensions brought about by contraction of the meshwork of longitudinal,
      circular and oblique layers of detrusor smooth muscles. Most in vitro
      physiological studies of the effects of aging on bladder function used the
      longitudinal detrusor. To understand the region specific effects of aging on
      bladder function the contractile responses of longitudinal and circular detrusor,
      and trigone segments of the bladder from young and old rats were monitored.
      MATERIALS AND METHODS: These studies were performed using male Fisher 344 rats 6
      months (young) and 27 months (old) old obtained through the National Institute on
      Aging. Each rat was anesthetized and the bladder was isolated. From each bladder
      a strip of longitudinal detrusor, circular detrusor and trigone was isolated and
      mounted in an in vitro multi-muscle chamber containing normal physiological
      solution at 37C. Isometric contractions of the 3 bladder strips were monitored
      after electrical field stimulation, 120 mM. potassium and 1 to 1,000 microM.
      bethanechol using a digital oscilloscope. RESULTS: In longitudinal detrusor from
      old rats there was no significant difference in the contractions evoked by
      electrical stimulation or high potassium but there was a significant reduction in
      contractions evoked by bethanechol compared with the responses of longitudinal
      detrusor from young rats. In circular detrusor from old rats there was a
      significant increase in contractions evoked by electrical stimulation and a
      slight increase in contractions produced by high potassium but no significant
      change in contractions evoked by bethanechol compared with the responses of
      circular detrusor from young rats. In trigone from old rats there was a
      significant decrease in contractions evoked by electrical stimulation, high
      potassium and bethanechol compared with young trigone. CONCLUSIONS: The reduction
      in contractions evoked by bethanechol suggests an age related reduction in
      muscarinic receptors in the longitudinal detrusor of aged rats. An increase in
      contractions evoked by electrical stimulation without a change in contractions
      evoked by bethanechol suggests a decrease in compliance caused by an increase in
      collagen in the circular detrusor of aged rats. A general decline in all
      contractile responses, including those evoked by high potassium, suggests reduced
      membrane depolarization in the trigone of aged rats. The effect of aging is
      specific to different regions and functional components of the bladder, probably
      due to changes in muscarinic receptors, collagen and depolarization.

PMID- 11458125
TI  - Reduction of bladder outlet resistance by selective stimulation of the ventral
      sacral root using high frequency blockade: a chronic study in spinal cord
      transected dogs.
AB  - PURPOSE: The use of electrical neural stimulation as treatment for neurogenic
      bladder is complicated by simultaneous contraction of the striated sphincter.
      This result is due to the composition of the ventral sacral roots, which contain
      somatic fibers innervating the external urethral sphincter and preganglionic
      parasympathetic fibers innervating the detrusor, among others. The somatic fibers
      have a larger caliber than the parasympathetic fibers and, as large diameter
      fibers, need a lower stimulus amplitude for activation than smaller fibers.
      Activation of the smaller fibers is always accompanied by activation of the
      larger fibers. We studied the effect of chronic application of selective combined
      low and high frequency current stimulation of the ventral sacral root on bladder
      evacuation and urethral resistance in chronically spinalized (spinal cord
      transected above the spinal micturition center) male dogs for daily bladder
      evacuation. MATERIALS AND METHODS: A total of 14 male mongrel dogs weighing 20 to
      25 kg. underwent transection of the spinal cord at the T10 vertebra. The S2
      ventral sacral root was wrapped with a bipolar electrode connected to a
      subcutaneous microstimulator. Daily bladder evacuation by neural stimulation with
      determination of the voided and residual urine volumes was done for 8 months. The
      animals were stimulated only with low frequency current during the 1-month spinal
      shock phase. Selective parameters of combined low frequency stimulation and high
      frequency blockade currents were subsequently applied for 6 months. For the last
      study month the animals were again stimulated by low frequency current alone.
      Bladder and urethral pressure as well as electromyography of the external
      urethral sphincter and pelvic floor muscles were evaluated monthly.
      Histopathological testing of the chronically stimulated nerve and external
      sphincter was performed. RESULTS: Of the 14 dogs 12 completed the followup study.
      During the shock phase with the application of low frequency only stimulation the
      animals voided 26% of mean functional bladder capacity with the early return of
      detrusor activity. Mean detrusor pressure plus or minus standard error of mean
      was 76.4 +/- 21.6 cm. water, while mean urethral pressure was 83.6 +/- 16.8 cm.
      water. During the application of selective combined low and high frequency
      stimulation 7 animals (58%) evacuated the bladder completely with post-void
      residual urine less than 10% of mean individual functional bladder capacity and 5
      (42%) had mean post-void residual urine less than 20% of mean individual bladder
      capacity. Mean detrusor pressure was 73.5 +/- 20 cm. water and mean urethral
      pressure was 44 +/- 7.3 cm. water. There was a 45.19% reduction in the mean
      electromyography activity of the external sphincter. Stimulation of the dogs for
      the last month by low frequency current resulted in the voiding of 33% of mean
      bladder capacity with an increase in mean urethral pressure and electromyography
      activity. CONCLUSIONS: These results of reducing external sphincter activity by
      the simultaneous application of high frequency current blockade of the somatic
      fibers and activation of the autonomic fibers of the bladder by low frequency
      stimulation are promising.

PMID- 11458126
TI  - Decreased trabecular smooth muscle and caveolin-1 expression in the penile tissue
      of aged rats.
AB  - PURPOSE: Because decreased trabecular smooth muscle content is reportedly
      associated with vasculogenic impotence in men, we performed a rodent study to
      investigate the effect of aging on trabecular smooth muscle content and caveolin
      1 protein expression in penile smooth muscle cells. MATERIALS AND METHODS: In 6
      young (age 3 months) and 6 old (age 24 months) rats erectile function was
      evaluated by cavernous nerve stimulation. At sacrifice penile tissue samples were
      collected for Western blot analysis, Masson's trichrome staining, caveolin-1
      immunostaining and electron microscopy. The percent of smooth muscle in the
      trabecular tissue was assessed by computer assisted image analysis. RESULTS: In
      the aged rats mean intracavernous pressure plus or minus standard deviation was
      decreased (70 +/- 8.8 versus 107 +/- 12.3 cm. water) and the latency period was
      increased (7.8 +/- 1.2 versus 4.5 +/- 0.5 seconds) significantly compared to
      values in the young rats (p <0.001). The mean ratio of trabecular smooth muscle
      to-connective tissue was also significantly altered in old versus young rats (27%
      +/- 2.9% versus 42.1% +/- 5.1%, p <0.001). Immunostaining for caveolin-1 was
      noted in each group in the sarcolemma of smooth muscle cells and endothelium of
      trabecular sinusoids but the staining pattern was less intense and the percent of
      smooth muscle positive for caveolin-1 was decreased in aged versus young rats
      (17.9% +/- 2.5% versus 27.5% +/- 3.6%, p <0.001). Moreover, young trabecular
      smooth muscle cells had more caveolae in the sarcolemma on electron microscopy
      and a higher expression of caveolin-1 protein on Western blot analysis. In
      contrast, higher endothelial nitric oxide synthase protein expression was noted
      in the penile tissue of old rats. CONCLUSIONS: In these aged rats the decreased
      ratio of trabecular smooth muscle-to-collagen and the reduced expression of
      caveolin-1 may contribute to erectile dysfunction.

PMID- 11458127
TI  - Antihypertensive drugs induce structural remodeling of the penile vasculature.
AB  - PURPOSE: There is a strong association between hypertension and erectile
      dysfunction. Studies of the treatment of hypertension have shown that some
      pharmacological agents are capable of inducing regression of the vascular
      structure during treatment. We determined whether penile vascular structure is as
      susceptible as other vascular beds to regression during antihypertensive drug
      treatment. MATERIALS AND METHODS: Adult spontaneously hypertensive rats were
      treated for 1 or 2 weeks with 30 mg./kg. enalapril daily, or for 2 weeks with 45
      mg./kg. hydralazine daily. Structurally based vascular resistance was determined
      in isolated penile and skeletal muscle vascular beds perfused with Tyrode
      dextran. A cumulative alpha1-adrenoceptor concentration constrictor response
      curve to 1 to 100 microg./ml. methoxamine was constructed and the maximum
      constrictor response (vasopressin, methoxamine and angiotensin II) indicating the
      tissue yield point (that is the average medial bulk of vascular smooth muscle)
      was determined. The hearts were excised and the ventricles were separated and
      weighed. RESULTS: Enalapril treatment progressively regressed cardiac and
      vascular structure during the 1 and 2-week treatment periods with a mean tissue
      yield point plus or minus standard deviation of -5.91% +/- 5.1% (p <0.05) and 
      12.1% +/- 6.0% (p <0.05), and a mean left ventricle mass of -11.8% +/- 2.2% (p
      <0.05) and -13.6% +/- 3.2% (p <0.05), respectively. Hydralazine treatment for 2
      weeks was less effective on vascular regression with a mean yield of -7.3% +/-
      2.9% (p <0.05) and it did not alter left ventricle hypertrophy compared with
      controls (3.7% +/- 5.0%). CONCLUSIONS: The data suggest that renin-angiotensin
      system inhibition may at least partially normalize penile vascular structure. The
      impact of these changes on erectile function must be determined.

PMID- 11458128
TI  - Characterization and localization of nitric oxide synthase isoforms in the BB/WOR
      diabetic rat.
AB  - PURPOSE: Erectile dysfunction is a common pathological development in individuals
      with diabetes mellitus. Nitric oxide synthase (NOS) is essential for regulation
      of normal penile erection and NOS protein activity has been shown to be altered
      with diabetes. Several different isoforms and subtypes of NOS exist. However,
      little is known about how the distribution and abundance of these isoforms are
      altered with diabetes. We characterized the distribution and abundance of NOS
      isoforms and explored how they are altered with diabetes and result in erectile
      failure. MATERIALS AND METHODS: In situ hybridization and quantitative reverse
      transcriptase-polymerase chain reaction were done to measure the abundance and
      distribution of NOS-Ia, NOS-Ib, NOS-Ic, NOS-II and NOS-III in control and
      diabetic (BB/WOR) rats. Protein was localized by immunohistochemical analysis and
      alterations in protein abundance with diabetes were examined by Western blot
      analysis. RESULTS: NOS-I, NOS-II and NOS-III were observed in the endothelium
      lining the cavernous spaces and in the epithelium of the urethra. NOS-I protein
      was also present in the nerves of control and diabetic penes. We observed an
      increase in NOS-II expression around the dorsal nerves of diabetic penes, a
      decrease in NOS-III expression in diabetic pelvic ganglia and a decrease in NOS
      Ib expression in the diabetic penis. NOS-I protein abundance was significantly
      decreased in diabetic pelvic ganglia. CONCLUSIONS: To our knowledge this is the
      first report of regional differences in the distribution of NOS-III in the
      urethra and altered NOS-Ib gene expression with diabetes.

PMID- 11458129
TI  - Mortality among seriously injured patients treated in remote rural trauma centers
      before and after implementation of a statewide trauma system.
AB  - BACKGROUND: Injury mortality in rural regions remains high with little evidence
      that trauma system implementation has benefited rural populations. OBJECTIVE: To
      evaluate risk-adjusted mortality in remote regions of Oregon before and after
      implementation of a statewide trauma system. RESEARCH DESIGN: A retrospective
      cohort study assessing injury mortality through 30 days after hospital discharge.
      SETTING: Nine rural Oregon hospitals serving counties with populations <18
      persons per square mile. SUBJECTS: Severely injured patients presenting to four
      level-3 and five level-4 trauma hospitals 3 years before and 3 years after trauma
      system implementation. MEASURES: Interhospital transfer, hospital death, and
      demise within 30 days following hospital discharge. RESULTS: A total of 940
      patients were analyzed. After trauma system implementation, patients presenting
      to level-4 hospitals were more likely transferred to level-2 facilities (P
      <0.001). Interhospital transfer times from level-3 hospitals lengthened
      significantly after system implementation (P <0.001). Overall mortality rates
      were higher in the postsystem period (8.3%) than the presystem period (6.7%), but
      not significantly. Controlling for covariates, no additional benefit to risk
      adjusted mortality was associated with trauma system implementation. Additional
      deaths, occurring after trauma system implementation, included head-injured
      patients transferred from rural hospitals to nonlevel-1 trauma center hospitals.
      CONCLUSIONS: Increased injury survival after Oregon trauma system implementation,
      demonstrated in urban and statewide analyses, was not confirmed in remote regions
      of the state. Efforts to improve trauma systems in rural areas should focus on
      the processes of care for head-injured patients transferred to higher designation
      trauma centers.

PMID- 11458130
TI  - Poison control centers and state-specific poisoning mortality rates.
AB  - OBJECTIVE: The purpose of this study was to compare poisoning mortality rates of
      states served by a poison control center certified by the American Association of
      Poison Control Centers (AAPCC) to those that are not served by a certified center
      because health policy has been based on certification status. METHODS: Poisoning
      mortality rates from 1993 to 1997 were obtained from a public use database of
      death certificates and were stratified by state and circumstance. Each state was
      classified as being fully served, partially served, or not served by an AAPCC
      certified center. States in one category of service for the entire 5 years were
      selected for analysis. RESULTS: During this 5-year period, 39 states exhibited a
      consistent category of poison control center services. The mortality rates per
      100,000 population during these 5 years were 5.93, 6.12, 6.01, 6.23, and 6.68
      respectively (P <0.05) for all 39 states. The mean 5-year mortality rate for
      states with certified poison control center services (7.08 +/- 2.59; n = 17) was
      higher (P <0.05) than those with noncertified service (5.17 +/- 1.46; n = 15) but
      not significantly different from those with partial certified service (6.25 +/-
      1.75; n = 7). CONCLUSION: Increased poisoning mortality rates were associated
      with AAPCC certification status and year. Poisoning mortality rates may not be an
      appropriate outcome measure of the impact of poison control centers, AAPCC
      certification notwithstanding, at this time. Basing poison control center-related
      policy on state-specific poisoning mortality rates can not be supported by these
      findings.

PMID- 11458131
TI  - Who uses flexible spending accounts: effects of employee characteristics and
      employer strategies.
AB  - BACKGROUND: Many large employers offer flexible spending accounts (FSAs) to
      shelter their employees' out-of-pocket medical expenses from taxes and thereby to
      encourage the purchase of health insurance policies with higher cost sharing.
      However, very little empirical research has examined the individual employee's
      decision to contribute to an FSA. OBJECTIVES: To estimate equations for the
      probability that single employees with no dependents and employees with family
      health insurance coverage will contribute to FSAs, and the amounts contributed by
      those with FSAs. RESEARCH DESIGN: An observational study of randomly-selected
      employees in 15 Minnesota firms matched with information on the strategies those
      firms use to promote FSAs. Measures of FSA participation were regressed on
      expected health care spending, employee socio-demographics, and employer
      strategies. SUBJECTS: 779 single employees with no dependents and 679 employees
      with family coverage. RESULTS: Education beyond high school increases the
      probability that both types of subjects will contribute to FSAs, with marginal
      effects ranging from 16 to 48 percent. The FSA contribution rate for families
      doubles when the family's marginal federal income tax rate increases from 15 to
      28 percent. Employer strategies to encourage participation are also effective in
      promoting FSAs. CONCLUSIONS: FSAs are used mainly by high-income and highly
      educated workers. We question whether this is an equitable use of the income tax
      code.

PMID- 11458132
TI  - Transforming self-rated health and the SF-36 scales to include death and improve
      interpretability.
AB  - BACKGROUND: Most measures of health-related quality of life are undefined for
      people who die. Longitudinal analyses are often limited to a healthier cohort
      (survivors) that cannot be identified prospectively, and that may have had little
      change in health. OBJECTIVE: To develop and evaluate methods to transform a
      single self-rated health item (excellent to poor; EVGGFP) and the physical
      component score of the SF-36 (PCS) to new variables that include a defensible
      value for death. METHODS: Using longitudinal data from two large studies of older
      adults, health variables were transformed to the probability of being healthy in
      the future, conditional on the current observed value; death then has the value
      of 0. For EVGGFP, the new transformations were compared with some that were
      published earlier, based on different data. For the PCS, how well three different
      transformations, based on different definitions of being healthy, discriminated
      among groups of patients, and detected change in time were assessed. RESULTS: The
      new transformation for EVGGFP was similar to that published previously. Coding
      the 5 categories as 95, 90, 80, 30, and 15, and coding dead as 0 is recommended.
      The three transformations of the PCS detected group differences and change at
      least as well as the standard PCS. CONCLUSION: These easily interpretable
      transformed variables permit keeping persons who die in the analyses. Using the
      transformed variables for longitudinal analyses of health when deaths occur,
      either for secondary or primary analysis, is recommended. This approach can be
      applied to other measures of health.

PMID- 11458133
TI  - Discussion of treatment options for early-stage breast cancer: effect of provider
      specialty on type of surgery and satisfaction.
AB  - OBJECTIVES: To describe the physicians with whom breast cancer patients discuss
      treatment options and assess whether discussing surgical options with a medical
      oncologist is associated with type of surgery and satisfaction. RESEARCH DESIGN:
      Medical record abstraction and survey. SUBJECTS: Women with early-stage breast
      cancer numbering 2,426 in two states-Massachusetts, where the rate of breast
      conserving surgery is high, and Minnesota, where it is lower. MEASURES: Receipt
      of breast-conserving surgery and satisfaction. RESULTS: Women in Massachusetts
      discussed breast cancer treatments with more physicians than women in Minnesota
      (mean 3.5 vs. 2.8; P <0.001) and more often discussed surgical options with a
      medical oncologist (52% vs. 28%; P <0.001). Using propensity score analyses, in
      Massachusetts, discussing surgical options with a medical oncologist was not
      related to type of surgery (adjusted difference in rate of breast-conserving
      surgery: 3.9%, 95% CI -3.6% to 11.5%) but was associated with greater
      satisfaction (adjusted difference: 8.1, 95% CI 2.0% to 14.2%). In Minnesota,
      discussing surgical options with a medical oncologist was associated with breast
      conserving surgery (adjusted difference: 12.6%, 95% CI 5.6% to 19.7%) with no
      difference in satisfaction (adjusted difference: -1.5%, 95% CI -6.8% to 3.8%).
      CONCLUSIONS: Outcomes associated with discussing surgical treatments with a
      medical oncologist vary with local care patterns. Where breast-conserving surgery
      is standard care, seeing a medical oncologist is not related to type of surgery,
      but is associated with greater satisfaction. Where it is not the standard, seeing
      a medical oncologist is associated with more breast-conserving surgery and
      equivalent satisfaction. These findings suggest that collaborative care may
      benefit women with respect to treatment selection or satisfaction.

PMID- 11458134
TI  - Evaluating diagnosis-based case-mix measures: how well do they apply to the VA
      population?
AB  - BACKGROUND: Diagnosis-based case-mix measures are increasingly used for provider
      profiling, resource allocation, and capitation rate setting. Measures developed
      in one setting may not adequately capture the disease burden in other settings.
      OBJECTIVES: To examine the feasibility of adapting two such measures, Adjusted
      Clinical Groups (ACGs) and Diagnostic Cost Groups (DCGs), to the Department of
      Veterans Affairs (VA) population. RESEARCH DESIGN: A 60% random sample of
      veterans who used health care services during FY 1997 was obtained from VA
      inpatient and outpatient administrative databases. A split-sample technique was
      used to obtain a 40% sample (n = 1,046,803) for development and a 20% sample (n =
      524,461) for validation. METHODS: Concurrent ACG and DCG risk adjustment models,
      using 1997 diagnoses and demographics to predict FY 1997 utilization (ambulatory
      provider encounters, and service days-the sum of a patient's inpatient and
      outpatient visit days), were fitted and cross-validated. RESULTS: Patients were
      classified into groupings that indicated a population with multiple psychiatric
      and medical diseases. Model R-squares explained between 6% and 32% of the
      variation in service utilization. Although reparameterized models did better in
      predicting utilization than models with external weights, none of the models was
      adequate in characterizing the entire population. For predicting service days,
      DCGs were superior to ACGs in most categories, whereas ACGs did better at
      discriminating among veterans who had the lowest utilization. CONCLUSIONS:
      Although "off-the-shelf" case-mix measures perform moderately well when applied
      to another setting, modifications may be required to accurately characterize a
      population's disease burden with respect to the resource needs of all patients.

PMID- 11458135
TI  - Resource utilization of patients with hypochondriacal health anxiety and
      somatization.
AB  - OBJECTIVES: To examine the resource utilization of patients with high levels of
      somatization and health-related anxiety. DESIGN: Consecutive patients on randomly
      chosen days completed a self-report questionnaire assessing somatization and
      health-related, hypochondriacal anxiety. Their medical care utilization in the
      year preceding and following completion of the questionnaire was obtained from an
      automated patient record. The utilization of patients above and below a
      predetermined threshold on the questionnaire was then compared. PATIENTS AND
      SETTING: Eight hundred seventy-six patients attending a primary care clinic in a
      large, urban, teaching hospital. OUTCOME MEASURES: Number of ambulatory physician
      visits (primary care and specialist), outpatient costs (total, physician
      services, and laboratory procedures), proportion of patients hospitalized, and
      proportion of patients receiving emergency care. RESULTS: Patients in the
      uppermost 14% of the clinic population on somatization and hypochondriacal health
      anxiety had appreciably and significantly higher utilization in the year
      preceding and the year following completion of the somatization questionnaire
      than did the rest of the patients in the clinic. After adjusting for group
      differences in sociodemographic characteristics and medical comorbidity,
      significant differences in utilization remained. In the year preceding the
      assessment of somatization, their adjusted total outpatient costs were $1,312
      (95% CI $1154, $1481) versus $954 (95% CI $868, $1057) for the remainder of the
      patients and the total number of physician visits was 9.21 (95% CI 7.94, 10.40)
      versus 6.33 (95% CI 5.87, 6.90). In the year following the assessment of
      somatization, those above the threshold had adjusted total outpatient costs of
      $1,395 (95% CI $1243, $1586) versus $1,145 (95% CI $1038, $1282), 9.8 total
      physician visits (95% CI 8.66, 11.07) versus 7.2 (95% CI 6.62, 7.77), and had a
      24% (95% CI 19%, 30%) versus 17% (95% CI 14%, 20%) chance of being hospitalized.
      CONCLUSIONS: Primary care patients who somatize and have high levels of health
      related anxiety have considerably higher medical care utilization than
      nonsomatizers in the year before and after being assessed. This differential
      persists after adjusting for differences in sociodemographic characteristics and
      medical morbidity.

PMID- 11458136
TI  - Does managed care enable more low income persons to identify a usual source of
      care? Implications for access to care.
AB  - BACKGROUND: By requiring or encouraging enrollees to obtain a usual source of
      care, managed care programs hope to improve access to care without incurring
      higher costs. OBJECTIVES: (1) To examine the effects of managed care on the
      likelihood of low-income persons having a usual source of care and a usual
      physician, and; (2) To examine the association between usual source of care and
      access. RESEARCH DESIGN: Cross-sectional survey of households conducted during
      1996 and 1997. SUBJECTS: A nationally representative sample of 14,271 low-income
      persons. MEASURES: Usual source of care, usual physician, managed care
      enrollment, managed care penetration. RESULTS: High managed care penetration in
      the community is associated with a lower likelihood of having a usual source of
      care for uninsured persons (54.8% vs. 62.2% in low penetration areas) as well as
      a lower likelihood of having a usual physician (60% vs. 72.8%). Managed care has
      only marginal effects on the likelihood of having a usual source of care for
      privately insured and Medicaid beneficiaries. Having a usual physician
      substantially reduces unmet medical needs for the insured but less so for the
      uninsured. CONCLUSIONS: Having a usual physician can be an effective tool in
      improving access to care for low-income populations, although it is most
      effective when combined with insurance coverage. However, the effectiveness of
      managed care in linking more low-income persons to a medical home is uncertain,
      and may have unintended consequences for uninsured persons.

PMID- 11458137
TI  - Comparison of the performance of two comorbidity measures, with and without
      information from prior hospitalizations.
AB  - OBJECTIVES: This study compares the performance of two comorbidity risk
      adjustment methods (the Deyo et al adaptation of the Charlson index and the
      Elixhauser et al method) in five groups of California hospital patients with
      common reasons for hospitalization, and assesses the contribution to model
      performance made by information drawn from prior hospital admissions. METHODS:
      California hospital discharge abstract data for the calendar years 1994 through
      1997 were used to create a longitudinal data set for patients in the five disease
      groups. Eleven logistic regression models were estimated to predict the risk of
      in-hospital death for patients in each group, with both comorbidity risk
      adjustment methods applied to patient information available from only the index
      hospitalization, and to information available from both the index and prior
      hospitalizations. RESULTS: For every comparison made, the level of statistical
      performance (area under the receiver operating characteristics curve)
      demonstrated by models using the Elixhauser et al method was superior to that of
      models using the Deyo et al adaptation method. Although most patients have
      information available from prior hospital admissions, this additional information
      yields only small improvements in the performance of models using either
      comorbidity risk adjustment method. CONCLUSIONS: Better discrimination is
      achieved with the Elixhauser et al method using only information from the index
      hospitalization than is achieved with the Deyo et al adaptation using information
      from all identified hospital admissions. Both comorbidity risk adjustment methods
      achieve their best performance when information from the index hospitalization
      and prior admissions is separated into independent indicators of comorbid
      illness.

PMID- 11458138
TI  - Multicomponent targeted intervention to prevent delirium in hospitalized older
      patients: what is the economic value?
AB  - INTRODUCTION: Delirium, or acute confusional state, is a common and serious
      occurrence among hospitalized older persons. Current estimates suggest that
      delirium complicates hospital stays for more than 2.3 million older persons each
      year, involving more than 17.5 million hospital days and accounting for more than
      $4 billion (1994 dollars) of Medicare expenditures. A 40% reduction was recently
      reported in the risk for delirium among hospitalized older persons receiving a
      multicomponent targeted risk factor intervention (MTI) strategy to prevent
      delirium, compared with subjects receiving usual hospital care.1 Before
      recommending that this preventive strategy be implemented in clinical practice,
      however, the cost implications must be thoroughly examined as well. METHODS: The
      present analysis performs net cost evaluations of the MTI for the prevention of
      delirium among hospitalized patients. Hospital charge and cost-to-charge ratio
      data are linked to a database of 852 subjects, who were treated with MTI or usual
      care. Multivariable regression methods were used to help isolate the impact of
      MTI on hospital costs. These results were then combined with our earlier work on
      the impact of the MTI on delirium prevention to assess the cost effectiveness of
      this intervention. RESULTS: The MTI significantly reduced nonintervention costs
      among subjects at intermediate risk for developing delirium, but not among
      subjects at high risk. When MTI intervention costs were included, MTI had no
      significant effect on overall health care costs in the intermediate risk cohort,
      but raised overall costs in the high risk group. CONCLUSIONS: Because the MTI
      prevented delirium in the intermediate risk group without raising costs, the
      conclusion reached is that it is a cost effective treatment option for patients
      at intermediate risk for developing delirium. In contrast, the results suggest
      that the MTI is not cost effective for subjects at high risk.

PMID- 11458139
TI  - Osteoinductive demineralized bone: what's the risk?

PMID- 11458140
TI  - Radiofrequency facet joint denervation in the treatment of low back pain: a
      placebo-controlled clinical trial to assess efficacy.
AB  - STUDY DESIGN: A prospective double-blind randomized controlled trial was
      performed. OBJECTIVE: To assess the efficacy of percutaneous radiofrequency
      articular facet denervation for low back pain. SUMMARY OF BACKGROUND DATA:
      Uncontrolled observational studies in patients with low back pain have reported
      some benefits from the use of facet joint radiofrequency denervation. Because the
      efficacy of percutaneous radiofrequency had not been clearly shown in previous
      studies, a randomized controlled trial was conducted to assess the efficacy of
      the technique for improving functional disabilities and reduce pain. METHODS: For
      this study, 70 patients with low back pain lasting of more than 3 months duration
      and a good response after intraarticular facet injections under fluoroscopy were
      assigned randomly to receive percutaneous radiofrequency articular facet
      denervation under fluoroscopic guidance or the same procedure without effective
      denervation (sham therapy). The primary outcomes were functional disabilities, as
      assessed by the Oswestry and Roland-Morris scales, and pain indicated on a visual
      analog scale. Secondary outcomes included spinal mobility and strength. RESULTS:
      At 4 weeks, the Roland-Morris score had improved by a mean of 8.4% in the
      neurotomy group and 2.2% in the placebo group, showing a treatment effect of 6.2%
      (P = 0.05). At 4 weeks, no significant treatment effect was reflected in the
      Oswestry score (0.6% change) or the visual analog pain score (4.2% change). At 12
      weeks, neither functional disability, as assessed by the Roland-Morris scale
      (2.6% change) and Oswestry scale (1.9% change), nor the pain level, as assessed
      by the visual analog scale (-7.6% change), showed any treatment effect.
      CONCLUSIONS: Although radiofrequency facet joint denervation may provide some
      short-term improvement in functional disability among patients with chronic low
      back pain, the efficacy of this treatment has not been established.

PMID- 11458142
TI  - Lessons from a trial of acupuncture and massage for low back pain: patient
      expectations and treatment effects.
AB  - STUDY DESIGN: A subanalysis of data derived from a randomized clinical trial was
      performed. OBJECTIVE: To evaluate the association of a patient's expectation for
      benefit from a specific treatment with improved functional outcome. SUMMARY OF
      BACKGROUND DATA: Psychosocial factors, ambiguous diagnoses, and lack of a clearly
      superior treatment have complicated the management of patients with chronic low
      back pain. The authors hypothesized that patient expectation for benefit from a
      specific treatment is associated with improved functional outcomes when that
      treatment is administered. METHODS: In a randomized trial, 135 patients with
      chronic low back pain who received acupuncture or massage were studied. Before
      randomization, study participants were asked to describe their expectations
      regarding the helpfulness of each treatment on a scale of 0 to 10. The primary
      outcome was level of function at 10 weeks as measured by the modified Roland
      Disability scale. RESULTS: After adjustment for baseline characteristics,
      improved function was observed for 86% of the participants with higher
      expectations for the treatment they received, as compared with 68% of those with
      lower expectations (P = 0.01). Furthermore, patients who expected greater benefit
      from massage than from acupuncture were more likely to experience better outcomes
      with massage than with acupuncture, and vice versa (P = 0.03). CONCLUSIONS: The
      results of this study suggest that patient expectations may influence clinical
      outcome independently of the treatment itself. In contrast, general optimism
      about treatment, divorced from a specific treatment, is not strongly associated
      with outcome. These results may have important implications for clinical trial
      design and recruitment, and may help to explain the apparent success of some
      conventional and alternative therapies in trials that do not control for patient
      expectations. The findings also may be important for therapy choices made in the
      clinical setting.

PMID- 11458144
TI  - An unexpected outcome during testing of commercially available demineralized bone
      graft materials: how safe are the nonallograft components?
AB  - STUDY DESIGN: Radiographic and histologic analyses of commercially available bone
      graft materials were performed. OBJECTIVE: To compare the osteoinductive efficacy
      of commercially available demineralized bone matrix material. SUMMARY OF
      BACKGROUND DATA: The relative in vivo bone formation and toxicology of the
      nonallograft components the make up various commercially available demineralized
      bone matrix products are not known. METHODS: An in vivo bone formation model was
      used in 30 athymic rats. Six different bone grafting materials were tested in
      subcutaneous and intermuscular locations. After 4 weeks, radiographic and
      histologic testing of bone formation was performed. RESULTS: Eight of nine rats
      implanted with Grafton demineralized bone matrix products died 1 to 4 days after
      implantation of the bone graft material. None of the remaining 10 animals
      implanted with the four other grafting materials died. The experiment was
      modified and completed with a lower dose of bone graft material. Pathologic
      analysis indicated that the cause of death was hemorrhagic necrosis of the
      kidneys, most likely caused by a toxic effect on the glomeruli and tubules. A
      possible causative factor may have been the glycerol in the graft material.
      CONCLUSIONS: Although the volume of Grafton product per kilogram of body weight
      used in this study was approximately eight times the maximum volume used in
      humans, the authors believe that this data must be reported because this product
      is used substantially in clinical settings. In addition, the osteoinductive
      performance and relative safety of the nonallograft components in all
      commercially available demineralized bone grafts are not known.

PMID- 11458146
TI  - Dose-dependent toxicity of a commercially available demineralized bone matrix
      material.
AB  - STUDY DESIGN: A relative risk assessment was performed to determine the safety of
      three commercially available Grafton demineralized bone matrix quantities used in
      athymic rats. OBJECTIVE: To evaluate the possible dose-dependent adverse effects
      of a commercially available demineralized bone matrix containing glycerol.
      SUMMARY OF BACKGROUND DATA: Commercially available Grafton demineralized bone
      matrix contains glycerol. The toxic effects of glycerol leading to acute renal
      failure have been documented. The toxicity of this glycerol-containing substance
      in higher doses has not been reported. METHODS: Three doses of Grafton putty were
      implanted in the upper hind limb muscles of athymic nude rats. The rats were
      observed for adverse effects and early death. Histologic studies were performed.
      RESULTS: All eight of the rats implanted with the highest dose of Grafton putty
      (0.008 mL/g) died, five of them within 12 hours of implantation and three in 48
      to 72 hours. One rat with the intermediate dose (0.004 mL/g) died within 12 hours
      of implantation. By 72 hours after implantation, three of the six rats (50%) with
      the intermediate dose had died. All six of the rats receiving the lowest dose
      (0.002cc/g) survived. The median lethal dose of Grafton putty in athymic rats was
      estimated to be 0.00469 mL/g body weight. Histologic analysis of the animals that
      received the high dose showed acute tubular necrosis, probably secondary to
      rhabdomyolysis. CONCLUSIONS: In athymic rats, large amounts of Grafton putty lead
      to death in a dose-dependent manner. Because the median lethal doses of Grafton
      putty (0.00469 mL/g) and glycerol (0.00442 mL/g) are comparable, a potential
      source of toxicity is the glycerol contained in the material. The results of this
      study suggest that high doses have the potential to cause acute renal failure.
      The authors suggest that clinical usage of Grafton putty in humans should be
      limited to no more than 2 mL/kg body weight of this material.

PMID- 11458147
TI  - Prediction of mechanical behaviors at interfaces between bone and two interbody
      cages of lumbar spine segments.
AB  - STUDY DESIGN: The effects of mechanical parameters at bone-implant interfaces of
      the lumbar spine segments were investigated under various combined loadings using
      the finite element method. OBJECTIVE: To investigate the mechanical behaviors at
      bone-cage interfaces of lumbar spine segments with two interbody cages (two
      thread inserts). SUMMARY OF BACKGROUND DATA: It is known that among many factors,
      relative micromotion at bone-implant interfaces can hinder bone growth into the
      surface pores of an implant. Loading conditions, mechanical properties of the
      materials, friction coefficients at the interfaces, and geometry of spinal
      segments would affect relative micromotion and spinal stability. In particular,
      relative micromotion is related closely to friction at bone-implant interfaces
      after arthroplasty. METHODS: A finite element model of human L3-L4 lumbar
      segments with two titanium interbody cages was constructed. This finite element
      model was used to investigate mechanical behavior at the bone-cage interface.
      Relative micromotion (slip distance on the contact surfaces), posterior axial
      displacement, and stress were predicted for changes of friction coefficients,
      loading conditions, and age-related material-geometric properties of the spinal
      segments. RESULTS: Relative micromotion (slip distance) at the interfaces was
      obvious at their edges under axial compression. The slip occurred primarily at
      the anterior edges under torsion with preload, whereas it occurred primarily at
      the edges of the left cage under lateral bending with preload. Relative
      micromotion at the interfaces increased significantly as the apparent density of
      cancellous bone or the friction coefficient of the interfaces decreased. A
      significant increase in slip distance at the anterior anulus occurred with an
      addition of torsion to the compressive preload. CONCLUSIONS: Relative micromotion
      is sensitive to the friction coefficient of the interfaces, the bone density, and
      the loading conditions. A reduction in age-related bone density is less likely to
      allow bone growth into surface pores of the cage. However, it is likely that the
      larger the disc area or pedicle diameter, the more stable the interbody fusion of
      the spinal segments.

PMID- 11458148
TI  - Subtotal corpectomy versus laminoplasty for multilevel cervical spondylotic
      myelopathy: a long-term follow-up study over 10 years.
AB  - STUDY DESIGN: A retrospective study was conducted. OBJECTIVE: To compare the long
      term outcomes of subtotal corpectomy and laminoplasty for multilevel cervical
      spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: No study has compared the
      long-term outcomes between subtotal corpectomy and laminoplasty for multilevel
      cervical spondylotic myelopathy. METHODS: In this study, 23 patients treated with
      subtotal corpectomy and 24 patients treated with laminoplasty were followed up
      for 10 to 14 years after surgery. Neurologic recovery, late deterioration, axial
      pain, radiographic results (degenerative changes at adjacent levels, alignment,
      and range of motion of the cervical spine), and surgical complications were
      compared between the two groups. RESULTS: No significant difference in neurologic
      recovery was found between the two groups 1 and 5 years after surgery, or at the
      latest follow-up assessment. Neurologic status deteriorated in one patient of the
      subtotal corpectomy group because of adjacent degeneration, and in one patient of
      the laminoplasty group because of hyperextension injury. Axial pain was observed
      in 15% of the corpectomy group and in 40% of the laminoplasty group (P < 0.05).
      In the corpectomy group, listhesis exceeding 2 mm developed at 38% of the upper
      adjacent levels, and osteophyte formation at 54% of the lower adjacent levels. In
      the laminoplasty group, kyphotic deformity developed in one patient (6%) after
      surgery. In the corpectomy group, the mean vertebral range of motion had
      decreased from 39.4 degrees to 19.2 degrees (49%) by the final follow-up
      assessment. In the laminoplasty group, the mean vertebral range of motion had
      decreased from 40.2 degrees to 11.6 degrees (29%) by the final follow-up
      assessment. Neurologic complications related to the surgery occurred in two
      patients (one myelopathy from bone graft dislodgement and one C5 root palsy from
      bone graft fracture) of the corpectomy group and four patients (C5 root palsy) of
      the laminoplasty group. All of these patients recovered over time. The corpectomy
      group needed longer operative time (P < 0.001) and tended to have more blood loss
      (P = 0.24). Six patients in the corpectomy group needed posterior interspinous
      wiring because of pseudarthrosis. CONCLUSIONS: Subtotal corpectomy and
      laminoplasty showed an identical effect from a surgical treatment for multilevel
      cervical spondylotic myelopathy. These neurologic recoveries usually last more
      than 10 years. In the subtotal corpectomy group, the disadvantages were longer
      surgical time, more blood loss, and pseudarthrosis. In the laminoplasty group,
      axial pain occurred frequently, and the range of motion was reduced severely.

PMID- 11458150
TI  - Childbearing, curve progression, and sexual function in women 22 years after
      treatment for adolescent idiopathic scoliosis: a case-control study.
AB  - STUDY DESIGN: A consecutive series of female patients with adolescent idiopathic
      scoliosis treated between 1968 and 1977, either with distraction and fusion using
      Harrington rods (n = 145) or with a brace (n = 122), were followed for at least
      20 years after completion of the treatment. OBJECTIVES: To determine the long
      term outcomes of childbearing and sexual life in women treated for adolescent
      idiopathic scoliosis, as compared with matched control subjects who did not have
      scoliosis. SUMMARY OF BACKGROUND DATA: The effect of pregnancy on curve
      progression is not established, and results are contradictory. Few reports exist
      on the social life (marriage, childbearing, and sexual function) of formerly
      treated individuals with scoliosis. METHODS: In this study, 136 surgically
      treated women (94%) and 111 brace-treated women (91%) completed the Scoliosis
      Research Society (SRS)/MODEM's questionnaire concerning childbearing and sexual
      life as a part of an unbiased personal follow-up examination. Of these, 129
      surgically treated and 105 brace-treated women also underwent a radiographic
      examination. The Cobb method was used to measure curve size in present and
      earlier examinations. An age-matched control group of 90 women was randomly
      selected and subjected to the same examinations. RESULTS: The mean age for all
      the groups was 40 years. Of the surgically treated and brace-treated women, 85%
      were or had been married, as compared with 82% of the control women. In the total
      cohort, 628 pregnancies had occurred. No significant mean difference existed
      between the groups in the number of children born (1.8 for the surgically
      treated, 1.9 for the brace-treated, and 2 for the control women) (P = 0.25). The
      patients in the brace-treated group had a significantly higher mean age at first
      pregnancy (28 years) than the control subjects (25.9 years) (P = 0.011), whereas
      the age for the surgically treated women (26.6 years) did not differ
      significantly from that for the brace-treated women. There were no significant
      differences between the groups in rates for low back pain (35% for the surgically
      treated, 43% for the brace-treated, and 28% for the control group) or for
      cesarean section (19% for the surgically treated, 14% for the brace-treated, and
      18% for the control group) during the first pregnancy. The rate of vacuum
      extractions was higher in the surgically treated group (16%) than in the control
      group (5%) (P = 0.036) or the brace-treated group(8%). Limitation of sexual
      function from the back was admitted by 33% of the surgically treated, 28% of the
      brace-treated, and 15% of the control women: surgically treated vs control
      subjects (P = 0.0042), brace-treated vs control subjects (P = 0.026), and brace
      treated vs surgically treated subjects (P = 0.57, a nonsignificant difference).
      These limitations were largely because of difficulties participating physically
      in activities or self-consciousness about appearance. Pain was a minor reason for
      limitation. There was no correlation between progression of the major or lumbar
      curve and number of pregnancies, or between curve progression and age at first
      pregnancy. CONCLUSIONS: Patients treated for adolescent idiopathic scoliosis
      appeared to function well with regard to marital status and number of children.
      The scoliotic curve did not seem to increase as a result of childbearing. Minor
      problems occurred during pregnancy and delivery. Some patients, however,
      experienced a slight negative effect in their sexual life.

PMID- 11458151
TI  - The in vivo dynamic response of the human spine to rapid lateral bend
      perturbation: effects of preload and step input magnitude.
AB  - STUDY DESIGN: A repeated measures design was used to determine the effects that
      combinations of two preloads and two added loads have on spine mechanics both
      before and during the response to the added load. OBJECTIVE: To investigate the
      effects of varying initial isometric and added step input load magnitudes on
      mechanical and electromyographic responses of the trunk during sudden loading
      that causes lateral bending moments. SUMMARY OF BACKGROUND DATA: Cocontractions
      of the antagonistic and agonistic muscles of the trunk are required for stability
      during loading of the spine. In several in vivo studies, it was observed that
      trunk muscle cocontraction serves a functional role before the application of
      unexpected or sudden loads. The response of agonistic and antagonistic trunk
      muscles to rapid lateral bend moments would provide further insight into the
      dynamic stability mechanisms of the spine. METHODS: In this study, 13 men
      maintained an upright standing posture while resisting the application of lateral
      bend moments produced by four different loading conditions comprising
      combinations of two preloads (5% or 15% of the maximum isometric lateral bend
      moment) and two added loads (20% or 30%). The preloading was used to develop
      different initial levels of trunk stiffness before the application of the added
      loads. The lateral bend moment and angular rotation of the trunk were measured,
      as well as the surface electromyogram amplitudes of the bilateral internal
      oblique, external oblique, rectus abdominus, lumbar erector spinae, and thoracic
      erector spinae muscles. Dependent measures were recorded during the steady state
      preload conditions, and peak values were recorded after the load was added.
      RESULTS: Higher added loads resulted in higher peak lateral bend rotations, and
      higher preloads resulted in lower rotations. The patterns of response were
      similar for the peak lateral bend moments and the electromyogram amplitudes from
      four of the five agonistic muscles. The thoracic erector spinae excepted, each of
      the other four muscles demonstrated larger responses in the agonistic muscles.
      However, all of the antagonistic muscles showed some increase in electromyogram
      activity in response to the added load. The thoracic erector spinae appeared to
      have the role of counteracting the flexor moments created by the abdominal
      muscles and the maintenance of spine stability. The agonistic external obliques
      and lumbar erector spinae had the largest responses to the added load. A
      comparison of the 35% loading conditions showed an increased response of the
      trunk to the 5% + 30% condition (with lower initial trunk stiffness), as compared
      with the 15% + 20% condition. CONCLUSIONS: The findings from this study show that
      higher levels of preactivation can serve to increase spine compression and trunk
      muscle stiffness, thereby attenuating the lateral displacements caused by rapid
      loading. Furthermore, antagonistic muscles were observed to respond rapidly to
      such perturbations with large increases in activation when preactivation and
      spine stability were low. The trunk muscles monitored all were larger,
      multisegmental muscles. The results from this study lend support to previous
      studies suggesting that the larger multisegmental muscles make a significant
      contribution to spinal stability.

PMID- 11458152
TI  - Intramuscular myoelectric activity and selective coactivation of trunk muscles
      during lateral flexion with and without load.
AB  - STUDY DESIGN: Myoelectric activity of trunk muscles was measured intramuscularly
      in six healthy subjects as they maintained static trunk postures at 0 degrees, 15
      degrees, and 30 degrees of lateral bending, unloaded or holding a 20-kg load in
      one hand alongside the body. OBJECTIVE: To determine the position and load
      dependency of the agonistic and antagonistic myoelectric responses of deep and
      superficial trunk lateral flexor muscles. SUMMARY OF BACKGROUND DATA: Loading of
      the trunk in lateral bending is associated with incidences of low back pain. The
      neuromotor control of muscles surrounding the spine may be decisive for its
      vulnerability. Earlier documentation of the activation pattern of trunk muscles,
      particularly those situated deeply, is incomplete. METHODS: Trunk angle was
      measured between S1-C7 and the vertical with a protractor. Electromyographic
      activity was recorded unilaterally from eight trunk muscles using intramuscular
      fine-wire electrodes inserted under the guidance of ultrasound. RESULTS: The
      electromyographic data showed that all muscles on the side contralateral to the
      load, except rectus abdominis, had their highest activity while loaded in the
      position most laterally flexed to the loaded side. The degree of bilateral
      coactivation was greater for the ventral than for the dorsal muscles.
      CONCLUSIONS: The myoelectric responses of most lumbar trunk muscles to static
      lateral flexion were dependent on trunk position and loading. The abdominal
      muscles demonstrated more coactivation than the other trunk muscles, and thus
      appeared to contribute more to trunk stabilization in laterally bent and loaded
      trunk positions.

PMID- 11458153
TI  - Natural history of posterior iliac crest bone graft donation for spinal surgery:
      a prospective analysis of morbidity.
AB  - STUDY DESIGN: A prospective study was conducted to examine bone graft donor site
      morbidity in 106 consecutive patients undergoing posterior spinal fusion.
      OBJECTIVES: To perform a prospective analysis of donor site morbidity, to
      document the incidence of major complications, and to collect information on the
      impact of autologous bone graft harvesting from the posterior iliac crest on the
      overall outcome of spinal surgery. SUMMARY OF BACKGROUND: Bone graft harvesting
      from the posterior iliac crest for spinal fusion is a source of significant
      morbidity. Previous retrospective case studies indicate that minor complications
      are common, but they do not define the natural history and complications of
      posterior iliac crest bone graft harvesting. METHODS: A standardized harvesting
      technique was used. At 3, 6, and 12 months after surgery, the patients completed
      a proforma questionnaire rating symptoms on a visual analog scale and underwent a
      postoperative examination by the surgeon. Finally, overall surgical outcome was
      assessed at 12 months. RESULTS: The major component of morbidity is donor site
      pain. Mean pain scores were 1.640 at 3 months, 1.812 at 6 months, and 1.207 at 12
      months. The pain at 12 months was significantly less than at 3 and 6 months (P =
      0.005), with a trend toward the highest scores at 6 months. A pain score of 0 was
      reported by 55% of the patients. Local sensory loss was found in 10% of the
      patients. Outcome assessment showed significant differences in morbidity for
      surgery performed at different spinal levels (P = 0.001), with lumbosacral
      surgery resulting in worse outcomes than either cervical (P < 0.05) or
      thoracolumbar (P < 0.05) surgery. Significantly higher visual analog scores were
      observed at 6 months in patients with poorer overall outcomes. CONCLUSIONS:
      According to this study, it is reasonable to reassure patients that a good result
      from spinal surgery will not be compromised by severe symptoms or major morbidity
      secondary to posterior iliac crest bone graft donation. Before surgery, patients
      may be advised concerning the risks of donor site pain, which improves
      significantly by 12 months, local tenderness, and uncommonly localized sensory
      loss.

PMID- 11458154
TI  - A new method for detecting pedicular wall perforation during pedicle screw
      insertion.
AB  - STUDY DESIGN: Sensitivity, specificity, and predictive value analyses of a method
      that can be used to detect pedicular wall perforation during pedicle screw
      insertion were assessed. OBJECTIVE: To determine the accuracy of observing the
      fatty material expelled during pedicle screw insertion for detecting pedicular
      wall perforations. SUMMARY OF BACKGROUND DATA: Although many methods for safe and
      accurate insertion of a pedicle screw are described, the rates of misplacement
      still are high, and complications may occur from improper placement of pedicle
      screws. Computer-assisted insertion techniques are reported to be very accurate,
      but these techniques are not yet commonly available. METHODS: In this study, 74
      pedicle screw insertions were observed for the material expelled after drilling
      for the pedicle screw. The outflows of blood and fatty particles were recorded
      separately. The position of the pedicle screws after surgery was verified by
      computed tomography. The specificity, sensitivity, positive and negative
      predictive values, and kappa statistics were assessed. RESULTS: Visible fatty
      particles were observed during 51 pedicle screw insertions. The histologic
      analysis showed that the fatty particles were coming from the bone marrow of the
      corpus. For the observation of fatty particles in detecting perforations along
      the pedicle screw pathway, the specificity was 98%, the sensitivity 73%, the
      positive predictive value 84%, the negative predictive value 95%, and the kappa
      statistic 0.74. CONCLUSIONS: The observation of fatty particles in the blood that
      comes out after drilling for the pedicle screw may indicate that there is no
      perforation along the pedicle screw pathway. The observation is easy to perform
      and does not require any special instruments. Therefore, it can be used alone or
      in combination with other methods to improve the accuracy of pedicle screw
      insertion.

PMID- 11458155
TI  - Osteoporotic spondylolisthesis: a case report.
AB  - STUDY DESIGN: A case of spondylolisthesis caused by osteoporosis is described.
      OBJECTIVES: To describe the different etiologies of spondylolisthesis, and to
      report a new cause of pathologic spondylolisthesis previously unreported in the
      literature. SUMMARY OF BACKGROUND DATA: The literature on the etiology of
      spondylolisthesis is reviewed. Pathologic spondylolisthesis has been described
      with structural abnormalities, such as Paget's disease and tumors, but not with
      osteoporosis. METHODS: A clinical and radiographic interpretation of the reported
      case is presented. RESULTS: De Novo development of a spondylolisthesis at L5-S1
      occurred by gradual elongation of the pars interarticularis over a period of 3
      years. CONCLUSION: The reported case adds to the literature on spondylolisthesis
      by describing another etiology for this conclusion. Osteoporotic
      spondylolisthesis may well be identified more frequently in the future given the
      high prevalence of osteoporosis in the elderly.

PMID- 11458156
TI  - Drop metastasis from sinonasal undifferentiated carcinoma: clinical implications.
AB  - STUDY DESIGN: The first reported case of multiple intradural, extramedullary
      spinal metastasis from sinonasal undifferentiated carcinoma is presented.
      OBJECTIVES: To elucidate the mechanisms by which metastatic disease invades the
      spinal axis, and to discuss the possibility of spinal drop metastasis from head
      and neck tumors that invade the dura. SUMMARY OF BACKGROUND DATA: Sinonasal
      undifferentiated carcinoma is a rare yet aggressive neoplasm of the upper airways
      and anterior skull base. This neoplasm is known to invade the cranial vault and
      brain locally. However, it has not previously been reported to seed the
      cerebrospinal fluid or result in drop metastasis. Such drop metastasis may result
      in significant neurologic deficit if not diagnosed and treated in a timely
      manner. METHODS: This report is based on a single patient treated by a
      multidisciplinary team from the departments of neurosurgery, otolaryngology, and
      radiation oncology at the University of Southern California School of Medicine.
      RESULTS: This patient initially underwent resection and local radiation therapy
      for sinonasal undifferentiated carcinoma of the anterior skull base. At the time
      of surgery, the tumor was noted to violate the dura and arachnoid along the
      subfrontal plane. At 11/2 years after the initial treatment, a bandlike
      distribution developed at T2 as well as paresthesias and numbness below that
      level. Imaging of the spine showed an intradural, extramedullary tumor at T2
      consistent with a schwannoma or meningioma. The patient underwent a laminectomy
      and tumor resection, which showed poorly differentiated sinonasal carcinoma.
      Local radiation therapy was administered, and the patient experienced complete
      recovery of neurologic function. Bilateral leg pain and weakness developed 14
      months later. Magnetic resonance imaging of the spine showed a new intradural,
      extramedullary lesion at T12, remote from the first lesion. This second
      metastasis was managed with surgical resection and adjuvant radiation therapy.
      CONCLUSIONS: This is the first reported case of a sinonasal carcinoma leading to
      intradural extramedullary metastasis. The primary tumor likely seeded the
      cerebrospinal fluid, thus resulting in drop metastasis. Patients with sinonasal
      undifferentiated carcinoma that invades the dura should be monitored closely for
      evidence of metastasis before symptoms develop.

PMID- 11458157
TI  - Vertebral osteomyelitis secondary to epidural catheter use: a case report.
AB  - STUDY DESIGN: A case of vertebral osteomyelitis secondary to epidural catheter
      use is reported. OBJECTIVE: To investigate the occurrence of vertebral
      osteomyelitis after the use of an epidural catheter. SUMMARY OF BACKGROUND DATA:
      Vertebral osteomyelitis is a rare but serious complication of epidural catheter
      use that apparently has not been reported previously in orthopedic literature.
      METHODS: A patient underwent abdominal surgery, and an epidural catheter was used
      for postoperative pain relief. He presented 3 months later with severe midlumbar
      pain. Magnetic resonance imaging and microbiologic examination of a specimen
      obtained at open biopsy were used in the investigation. RESULTS: Magnetic
      resonance imaging suggested vertebral osteomyelitis involving L1-L3. The patient
      underwent open debridement and posterior instrument stabilization. Biopsies taken
      from L3 pedicles yielded Pseudomonas aeruginosa, which had been recovered earlier
      from the epidural catheter tip. CONCLUSION: Vertebral osteomyelitis is a rare but
      serious complication of epidural catheter use.

PMID- 11458158
TI  - Intraspinal metallosis causing delayed neurologic symptoms after spinal
      instrumentation surgery.
AB  - STUDY DESIGN: Two cases of intraspinal metallosis causing delayed neurologic
      symptoms secondary to spinal instrumentation surgery are reported. OBJECTIVE: To
      present an unusual delayed neurologic complication after spinal instrumentation
      surgery. SUMMARY OF BACKGROUND DATA: Metal-related complications caused by
      orthopedic implants have long been a concern in the field of arthroplasty or
      internal fixation of fractures, but no such complications have been reported for
      spinal instrumentation. METHODS: Retrospective case report of two patients with
      degenerative scoliosis who presented with delayed neurologic symptoms months to
      years after uneventful, but without secondary degenerative changes or
      dislodgement of the implants. RESULTS: In both reported cases, a granulation
      tissue mass characterized by marked metallosis had been formed in the spinal
      canal adjacent to a loosened laminar hook. CONCLUSIONS: Intraspinal metallosis
      should be kept in mind as a rare cause of delayed neurologic symptoms after
      spinal instrumentation surgery. With the metal implants in place, myelography was
      the sole informative examination for diagnosis.

PMID- 11458160
TI  - Spinal-thoracic dumbbell meningioma: a case report.
AB  - STUDY DESIGN: Total excision of a large dumbbell cervicothoracic intra- and
      extraspinal meningioma that had grown into the posterior mediastinum is
      described. This excision involved a two-step neurosurgical-thoracosurgical
      procedure within a short interval. OBJECTIVES: To document that the described
      laminectomy and thoracotomy techniques are adequate, safe, and effective for the
      treatment of this intra- and extraspinal meningioma lesion. SUMMARY OF BACKGROUND
      DATA: The management of intra- and extraspinal dumbbell tumors is based on
      anecdotal reports of mostly neurinomas, and thus remains a controversial issue.
      Even large series of spinal meningiomas lack adequate information on how best to
      treat large cervicothoracic meningiomas. METHODS: The authors have modified
      standard techniques used for resection of spinal and mediastinal tumors,
      respectively, adapting them for a large, invasive dumbbell meningioma in a 72
      year-old lady. The patient initially underwent laminectomy and microsurgical
      excision of the intraspinal tumor portions encasing vascular structures. A week
      thereafter, a thoracotomy was performed, and the mediastinal tumor portions were
      removed completely. RESULTS: Restitution was remarkably good. The patient, who
      had been unable to walk on her own, regained some mobility. At this writing, she
      was able to walk considerable distances without support. There was no evidence of
      tumor recurrence during a follow-up interval of 3 years. CONCLUSIONS: The authors
      recommend a two-staged procedure for complete excision of a large spinal-thoracic
      meningioma. Even in elderly patients with major neurologic deficits, an
      impressive recovery can be achieved with such lesions.

PMID- 11458162
TI  - A new class of COX-2 inhibitors offer an alternative to NSAIDS in pain management
      after spinal surgery.

PMID- 11458165
TI  - Re: Four-year follow-up results of lumbar spine arthrodesis using Bagby and
      Kuslich lumbar fusion cage.

PMID- 11458166
TI  - Re: Four-year follow-up results of lumbar spine arthrodesis using Bagby and
      Kuslich lumbar fusion cage.

PMID- 11458168
TI  - In vivo changes in the neuroforaminal size at flexion-extension and axial
      rotation of the cervical spine in healthy persons examined using kinematic
      magnetic resonance imaging.
AB  - STUDY DESIGN: In vivo flexion-extension and axial rotation magnetic resonance
      imaging (MRI) studies of the cervical spine were performed inside a positioning
      device. OBJECTIVE: To determine the functional changes of neuroforaminal size
      that occur during flexion-extension and axial rotation of the cervical spine in
      healthy persons. SUMMARY OF BACKGROUND DATA: Kinematic MRI studies of the
      cervical spine were performed to obtain detailed information about the functional
      changes that occur in neuroforaminal size during flexion-extention and axial
      rotation. The results were compared with published data of in vitro functional
      flexion-extension and axial rotation studies of the cervical spine. METHODS:
      Inside a positioning device, the cervical spines of 30 healthy persons were
      examined in a whole-body magnetic resonance scanner from 40 degrees of flexion to
      30 degrees of extension at nine different angle positions. In addition, axial
      rotation was performed at neutral position (0 degrees ) and at 20 degrees and 40
      degrees of axial rotation to both sides. The images were analyzed with respect to
      the neuroforaminal size at each position using a reformatted 3D-FISP sequence.
      RESULTS: At flexion, widening of the neuroforaminal size of up to 31% (compared
      with neutral position, 0 degrees ) was observed. Conversely, at extension a
      decrease in the size of the neuroforamen of up to 20% was recognized. At 20
      degrees and 40 degrees of ipsilateral rotation of the head, a reduction in the
      neuroforaminal size of up to 15% and 23%, respectively, compared with the neutral
      position was noted. In contrast, a widening of the foraminal size was recognized
      on the contralateral side of 9% and 20% at 20 degrees and 40 degrees rotation.
      Statistically significant differences (p <== 0.05) were found in the
      neuroforaminal size between different degrees of flexion and extension and in
      addition for axial rotation compared to neutral position (0 degrees ).
      CONCLUSION: Compared with the results of previous biomechanical studies of human
      cadaver cervical spines, kinematic MRI provides additional noninvasive data
      concerning the physiological changes of the neuroforaminal size during flexion
      extension and axial rotation in healthy individuals.

PMID- 11458169
TI  - A correlation between magnetic resonance imaging and electrophysiological
      findings in cervical spondylotic myelopathy.
AB  - STUDY DESIGN: Correlation between compressed spinal cords on magnetic resonance
      imaging (MRI) and electrophysiological findings in cervical spondylotic
      myelopathy patients. OBJECTIVE: To clarify the correlation between spinal-cord
      evoked potentials and MRI measurements of compressed spinal cords in patients
      with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Compression of
      the spinal cord does not always cause clinical symptoms and it is difficult to
      infer the degree of dysfunction of the spinal cord from MRI findings. METHODS:
      Seventeen patients with cervical spondylotic myelopathy were examined with MRI
      and spinal-cord-evoked potentials before surgery. Using abnormality in spinal
      cord-evoked potentials as indicators of spinal cord morphology, spinal-cord
      transverse area and compression ratios (central and 1/4-lateral) were measured on
      T1-weighted axial imaging. The correlations between these dimensions and
      electrophysiological findings were investigated. RESULTS: The mean preoperative
      transverse area of the spinal cord was 47.13 mm2. The mean preoperative central
      compression ratio of the spinal cord was 34.4%. The mean preoperative 1/4-lateral
      compression ratio of the spinal cord was 27.5%. A correlation (Spearman r=0.65, P
      < 0.01) was observed between the 1/4-lateral compression ratio of the spinal cord
      and the amplitude ratio of spinal-cord-evoked potentials after electric
      stimulation of the brain (Br(E)-SCEPs). CONCLUSIONS: The preoperative 1/4-lateral
      compression ratio of the spinal cord was found to reflect the degree of
      dysfunction of the corticospinal tracts.

PMID- 11458170
TI  - Root and spinal cord compression from methylmethacrylate vertebroplasty.
AB  - STUDY DESIGN: Case report and literature review. OBJECTIVES: Clinicians use
      methylmethacrylate vertebroplasty to treat vertebral hemangiomas, metastases, and
      osteoporotic fractures. Cement may leak out of the vertebral body and compress
      the adjacent spinal cord and nerve roots. We review a case of nerve-root and cord
      compression from methylmethacrylate extrusion during vertebroplasty. SUMMARY OF
      BACKGROUND DATA: A 50-year-old female presented with disabling thoracic back
      pain. A metastasis to T1 was discovered, with collapse of the vertebral body but
      without cord compression. Methylmethacrylate vertebroplasty was performed. After
      injection, portable computed tomography (CT) showed a leakage of
      methylmethacrylate into the C8 and T1 foramina and spinal canal. Radiculopathy
      and myelopathy developed. Surgical decompression using the anterior approach was
      necessary. METHODS: Case report. RESULTS: Early surgical intervention
      decompressed the neural elements and relieved the neurological deficits.
      CONCLUSIONS: Neurologic complications of methylmethacrylate vertebroplasty
      necessitate active involvement of spine surgeons in patient evaluation and
      management.

PMID- 11458171
TI  - Contained rupture of the aneurysm of common iliac artery associated with pyogenic
      vertebral spondylitis.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To report and discuss a case of
      contained rupture of the aneurysm of common iliac artery associated with pyogenic
      vertebral spondylitis, so that investigators and practitioners may avoid the
      diagnostic and therapeutic pitfalls associated with pyogenic vertebral
      spondylitis and aortic disease. SUMMARY OF BACKGROUND DATA: Pyogenic vertebral
      spondylitis is a rare disorder that may have serious consequences, including
      death, if it is not diagnosed promptly and treated effectively. The association
      of pyogenic vertebral spondylitis with infection of the aorta is a rare but
      potentially fatal condition that requires prompt diagnosis and aggressive
      surgical and medical therapy. To our knowledge, this is the first report of a
      contained rupture of the aneurysm of common iliac artery case associated with
      pyogenic vertebral spondylitis resulting from an infection with Bacteroides
      fragilis,although Salmonellae infections are commonly associated with vertebral
      osteomyelitis and lesions of the contiguous aorta. METHODS: A 60-year-old man
      with chronic lower back pain began to experience a severe pain and had increased
      difficulty in walking. An MRI scan showed an increased signal in the L4-L5 disc
      space and an abscess extending into the spinal canal. The presumptive diagnosis
      was infective spondylitis. While performing a CT-guided needle biopsy, an
      unexpected contained rupture of the aneurysm of common iliac artery was
      discovered. RESULTS: A wide resection of all infected tissue, including the right
      common iliac artery and bony lesions, was performed in combination with
      antimicrobial therapy. A cryopreserved aortic allograft was used to reconstruct
      the artery, and an iliac strut graft was used to fill the debrided vertebral
      cavity. The patient's postoperative recovery was uneventful. CONCLUSION: The
      coexistence of pyogenic vertebral spondylitis and lesions of the aorta is rare,
      but may be lethal if not diagnosed promptly and treated effectively. Even if a
      patient's condition is stable and the hematocrit is normal, it is important to
      consider the possibility of a contained rupture of a mycotic abdominal aneurysm
      in all patients with vertebral osteomyelitis who have acute episodes of unusual
      severe back pain. CT is sometimes more beneficial than MRI in the identification
      and characterization of contained rupture of aneurysms.

PMID- 11458172
TI  - [Progressive disassembly of genes implicated in different forms of familial
      paraganglioma of the carotid glomus: is the mitochondria implicated in
      tumorgenesis?].

PMID- 11458173
TI  - [Identification of eight new mutations in the c-erbAB gene of patients with
      resistance to thyroid hormone].
AB  - Resistance to thyroid hormone (RTH) is a rare genetic disorder, usually
      associated with different mutations in the c-erbAB gene that encodes the beta
      type receptor of thyroid hormone (TRB). It is characterized by elevated serum
      thyroid hormone and inappropriate TSH secretion. The numerous mutations so far
      detected are clustered in three hot spot areas in the ligand binding domain of
      TRB. In the context of a national survey we have detected 16 different mutations
      in the c-erbAB gene, in 22 families presenting with RTH. Eight of these mutations
      had not been described previously. Two are located in an area not known to harbor
      naturally occurring mutations. This observation could lead to define a fourth
      cluster of mutations in the c-erbAB gene.

PMID- 11458174
TI  - Solitary adrenal gland metastasis of a follicular thyroid carcinoma presenting
      with hyperthyroidism.
AB  - Follicular thyroid carcinoma typically manifests under euthyroid conditions, and
      diagnostic scintigraphy usually identifies a cold nodule. Sometimes, such tumors
      can appear in the context of hyperthyroidism, which can be caused by a toxic
      multinodular goitre, a toxic adenoma, or even carcinoma. We report a case of
      follicular thyroid carcinoma discovered after surgical treatment of a toxic
      multinodular goiter, in which solitary adrenal gland metastasis was detected five
      years later. A (131)I whole body scan is the diagnostic method of choice for
      functioning thyroid metastasis.

PMID- 11458175
TI  - [Thyroid nodules: histological approach using microbiopsies obtained with a
      biopsy gun: preliminary study].
AB  - Surgery remains the safest treatment of thyroid nodules, even though the
      frequency of the cancer is low. Modern diagnostic techniques are aimed at
      reducing the number of useless surgical interventions. These techniques rely on
      diagnostic patterns; cytology plays a predominant role. Nevertheless, it is
      difficult do obtain a sample with enough cellular material for the cytology
      study. The pathologist must also have skilled experience to provide a reliable
      reading. Surgical biopsies are no longer performed due to the risk of severe
      complications. Microbiopsy techniques have been greatly improved and are now
      widely used for many organs. In this preliminary study, we performed 18
      microbiopsies of thyroid nodules measuring less than 1 cm in 18 patients using a
      20-gauge biopsy gun. We had one complication: a cervical hematoma after the third
      biopsy in the series that resolved rapidly. The pathology examination identified
      follicular adenoma in 14 cases, and Hashimoto thyroiditis in 1. Three small
      samples contained subnormal thyroid vesicles with suspicion of adenoma for one.
      All samples were diagnostic, more cellular and easier to read than cytology
      specimens. This study points to the usefulness of these microbiopsy techniques
      for histological analysis, particularly applicable to thyroid nodules, and the
      obvious benefit in biopsy and reading efficiency.

PMID- 11458176
TI  - [Thyrotoxicosis hepatitis: a case report].
AB  - Abnormal liver function in thyroid disorders may be secondary to thyrotoxicosis
      or to autoimmune injury to the liver. We report the case of a 36-year-old female
      who developed jaundice and pruritus with mild cholestasis and moderately elevated
      transaminase levels. The diagnosis of Graves' disease was made shortly
      thereafter. Laboratory findings were: alanine and aspartate aminotransferase 219
      (IU/I (N: 9-50) and 102 IU/I (N: 10-15) respectively, alkaline phosphatase 336
      IU/I (N: 40-135), bilirubin 24 micromol/I (N: 2-23), and gamma-glutamyl
      transpeptidase 232 IU/I (N: 9-43). Abdominal ultrasonography showed normal bile
      ducts; echocardiography ruled out heart failure; viral and autoimmune markers for
      hepatitis and cirrhosis were negative. Percutaneous liver biopsy showed moderate
      intrahepatic steatosis, anisokaryosis, lymphocyte infiltration in the portal
      areas, and Kupffer cell hyperplasia. Outcome was favorable after seven months of
      iodine therapy, confirming the diagnosis of thyrotoxicosis hepatitis.

PMID- 11458177
TI  - [Regulation of lipid metabolism by the orphan nuclear receptors].
AB  - Lipids (cholesterol and fatty acids) are essential nutriments and have a major
      impact on gene expression. Hence cholesterol intracellular concentration is
      precisely controlled by some complex mechanisms involving transcriptional
      regulations. The excess of cholesterol in cells is converted into oxysterols.
      These cholesterol metabolites are important signalisation molecules that modulate
      several transcription factors involved in cholesterol homeostasis. Schematically,
      regulation of cholesterol homeostasis is achieved by three different but
      complementary pathways: 1) endogeneous biosynthesis, which corresponds to the de
      novo synthesis of cholesterol and is controlled by sterol response element
      binding proteins (SREBPs); 2) the transport, intracellular absorption and
      esterification of the cholesterol; 3) the metabolic conversion into bile acids
      and steroid hormones. These three pathways are closely linked, however we will
      schematically detail the role of the orphan nuclear receptors on the modulation
      of these three levels of regulation. Phenotype analyses of knock-out or
      transgenic mice pointed out the respective role of the "enterohepatic" orphan
      nuclear receptors LXRalpha, LXRB, FXR, LRH-1, the nuclear receptor PPARalpha, and
      their heterodimeric partner RXR, as well as the peculiar receptor SHP. Complex
      feed-backs have thus been demonstrated. These transciptional regulations have
      several targets: the P450 cytochromes involved in the bile acid synthesis Cyp7a1
      and Cyp8b1; the intestinal bile acid binding protein IBABP; the cholesteryl ester
      transfert protein CETP and phospholipid transfert protein PLTP, both involved in
      the HDL catabolism; the ABC cholesterol transporters ABCG1/ABC8 and ABCAI/ABCI.
      At last it seems that polyunsaturated fatty acids could activate LXRalpha
      transcription through its activation by PPARalpha. In the near future, the
      identification and study of new target genes by transcriptomic or proteomic
      analyses will allow a better understanding of lipid homeostasis in physiological
      as well as pathophysiological conditions.

PMID- 11458180
TI  - [Autopsy].
AB  - The disappearance of autopsies is of concern in Neurology for three reasons: in
      some cases, such as degenerative diseases, the predictive value of clinical
      diagnosis is still poor; autopsy is, for Neurology, an important piece of the
      public health watch; the modern post-genomic research needs tissue samples that
      cannot be obtained by other means for ethical reasons. The main rules of autopsy
      in France, including the pitfalls of legislation, are recalled. The prerequisites
      for a renewing of autopsy, the modifications that are required, the procedure to
      explain its importance in the hospital, among neurologists, and in the society
      are considered.

PMID- 11458181
TI  - [Atherosclerotic aortic plaques and risk of embolic stroke].
AB  - There is mounting evidence to implicate complex atherosclerotic aortic plaques as
      a significant independent risk factor for embolic stroke. Ulcerated plaques at
      autopsy, plaques thicker than 4 to 5mm at transesophageal echocardiography and
      those with mobile components are more likely to be associated with stroke. Mobile
      thrombus in the lumen may be a source of cerebral emboli. Among patients with
      ischemic stroke, those with plaques thicker than 4mm in the aortic arch have the
      highest risk of recurrent stroke, myocardial infarction, other vascular event
      including vascular death. However, since no randomized trials have been conducted
      to evaluate the role of any antithrombotic therapies in patients with aortic
      atheroma, no recommendation can be made regarding the best treatment strategies.
      Antiplatelet agents, oral anticoagulant, thrombolytic therapy, and elective
      surgical endarterectomy or graft replacement are all reasonable options that have
      been proposed and that must be evaluated in term of benefit/risks ratio in
      specific randomized controlled trials. Meanwhile, antiplatelet agents and
      aggressive risk factor management appear to be the first line treatment. No
      recommendation can be made to use oral anticoagulation in these patients nor for
      a target INR. Concerns also exist on the possibility of anticoagulation driven
      cholesterol embolism in these patients.

PMID- 11458182
TI  - Genetic epidemiology of Creutzfeldt-Jakob disease in Europe.
AB  - The prion protein gene was studied in patients with definite or probable
      Creutzfeldt-Jakob disease (CJD) registered by national CJD units of 6 European
      countries. The role of genetic factors in CJD was also investigated by comparing
      the frequencies of a family history of dementia and Parkinson's disease in CJD
      cases and matched controls. Codon 129 genotype was examined in 337 CJD cases of
      whom 73.2 p. 100 were homozygous for methionine, 10.9 p. 100 were homozygous for
      valine and 15.7 p. 100 were heterozygous. The genotype frequencies were not
      statistically different across countries. Future differences, if any, would
      constitute a meaningful signal for the surveillance of CJD in Europe. A prion
      protein gene mutation was found in 14.5 p. 100 of CJD cases; only 40 p. 100 of
      them had a known family history of CJD. The case-control study showed that
      positive family histories of dementia and Parkinson's disease were both
      associated with CJD. Although recall bias is the most likely explanation for this
      finding, the hypothesis that neurodegenerative diseases might share unknown
      genetic risk factors can also be considered.

PMID- 11458183
TI  - [Localizing and prognosis value of 99Tcm-ECD spect in patients with refractory
      temporal lobe epilepsies].
AB  - Interictal and ictal 99Tcm ECD-SPECT were retrospectively studied in 46 patients
      with refractory temporal lobe epilepsy. Forty two of these patients underwent an
      anterior temporal lobectomy with amygdalo-hippocampectomy or a cortical
      resection. SPECT findings as indicator of localization for the epileptogenic zone
      (EZ) and surgical prognosis were validated by comparison with other
      investigations including video-EEG monitoring with surface electrodes in all the
      patients, intracranial electrodes in 18 patients and the results of post-surgery
      outcome. Reliability of SPECT for localizing the epileptogenic zone (EZ) was
      found for mesial temporal epilepsy (28 patients) and the presumed bilateral
      temporal epilepsies (7 patients). In these latter cases, ECD-SPECT findings may
      serve to replace invasive methods with use of intracranial electrodes. SPECTs
      were unreliable when EZ was undetermined whether mesial or lateral by other non
      invasive investigations. Unilateral mesial temporal hyperperfusion associated
      with hypoperfusion of contralateral mesial structures evidenced by ictal SPECTs
      appear to be preoperative criteria for a successful outcome after surgery.

PMID- 11458184
TI  - [Therapeutic efficacy during active phases of multiple sclerosis: gait analysis
      and comparison with the EDSS score].
AB  - Fifteen patients experiencing a flare-up of multiple sclerosis were given 1 g
      methylprednosolone per day for 5 days. The EDSS score and gait analysis using
      spatio-temporal variables were recorded for these patients on days 0, 5 and 45.
      Both methods evidenced significant improvement but the significance was observed
      between day 0 and day 5 for the EDSS and between day 5 and 45 for gait speed and
      between day 0 and 45 for step rate. Gait speed was correlated with the pyramidal
      scale but not with the other functional scales of the EDSS. These results suggest
      that EDSS and spatio-temporal gait analysis are different tools for the
      assessment of therapeutic effect. Gait analysis can provide a precise
      quantitative assessment of the locomotor handicap as a function of the proposed
      treatment.

PMID- 11458185
TI  - [Atypical CADASIL phenotypes and pathological findings in two new French
      families].
AB  - Atypical phenotypes of CADASIL and corresponding anatomical data in two cases are
      described in 6 members of 2 new French families. In the first family, 4 cases in
      the same kindred were probably affected, two of them with a predominant
      psychiatric presentation, two others with dementia and a pseudo-bulbar syndrome
      of progressive evolution. No history of migraine or ischemic event were
      documented in any. In the propositus, the diagnosis was documented by skin
      biopsy, Notch 3 gene mutation and autopsy after the patient had died when 67
      years old, 8 years after onset. Brain examination showed a widespread
      leukoencephalopathy with subcortical infarcts. Characteristic granular lesions of
      the small arteries of the brain and other organs were observed. In the second
      family, two cases are reported. One patient died when 63 years old after a
      subacute evolution mimicking intracranial hypertension. The anatomical diagnosis
      was retrospectively proven typical of CADASIL with Notch 3 immunostaining of
      arterial smooth muscle cells. The other case had a progressive evolution over 20
      years of limb paresthesia with a mild spasticity diagnosed as a progressive form
      of multiple sclerosis. It was followed by a pseudo-bulbar syndrome and a mild
      subcortical dementia without acute ischemic attack. The diagnosis was confirmed
      by skin biopsy and mutation of the Notch 3 gene. This report illustrates

PMID- 11458186
TI  - [Myelopathy - Sjogren's syndrome association: analysis of clinical and
      radiological findings and clinical course].
AB  - Myelopathies associated with Sjogren's syndrome has been rarely described
      especially concerning magnetic resonance imaging (MRI) and treatment aspects. The
      aim of this study was to determine the clinical, laboratory and radiological
      features of myelopathies occurring in Sjogren's syndrome. Eleven patients were
      studied, 7 with an acute myelopathy and 4 with a chronic form. Acute myelopathy
      were clinically severe with a feature of transverse myelitis necessitating
      immunosuppressive drugs. On the other hand, chronic forms were closely similar to
      progressive multiple sclerosis (MS), for clinical and laboratory data. In 7 cases
      optic neuritis was found associated with myelopathy and fulfilled the diagnostic
      criteria of Devic's syndrome in 4 cases. The diagnosis of myelopathy associated
      with Sjogren's syndrome may be difficult especially compared with MS, HTLV1 or
      HIV myelopathy and sarcoidosis, in the chronic form but also with other
      vasculitis, MS or viral infection in the acute forms. However, in this last form,
      magnetic resonance imaging and cerebrospinal fluid data should bring to the
      diagnosis of Sjogren syndrome and confirmed by appropriate tests. This diagnosis
      will have direct consequences for an early treatment by immunosuppressive drugs.

PMID- 11458187
TI  - [Recurrent encephalopathy after small bowel resection. Implication of D-lactate].
AB  - Recurrent episodes of confusion are most commonly due to transient brain
      dysfunction related to vascular, epileptic or metabolic abnormalities. We report
      here a 54-year-old patient who, in the months following an extensive surgery of
      the small intestine, developed several acute confusional episodes characterized
      by encephalopathic signs (such as behavioral changes, desorientation and
      somnolence), ataxia, nystagmus and dysarthria. A number of metabolic changes were
      demonstrated during the episodes, including metabolic acidosis with increased
      anion gap and an elevated blood level of D-lactate. Symptoms disappeared after
      treatment with antibiotics. D-lactate encephalopathy is a rare cause of recurrent
      confusion which could be suspected based on a characteristic association of
      clinical signs. Diagnosis is confirmed by appropriate dosages. We discussed the
      possible mechanisms leading to confusional episodes.

PMID- 11458188
TI  - [High-frequency synchronous bursts firing associated with asynchronous midbrain
      tremor].

PMID- 11458189
TI  - [Epileptic seizures, hemiplegia and hyperglycemia: late discovery of a localized
      cortical dysplasia].
AB  - A 56-year-old woman was hospitalized with a right hemiplegia and aphasia evoking
      a cerebral infarction. In fact the neurologic deficits were of post-ictal origin,
      secondary to a partial epilepsy which began a few weeks before, at the same time
      as a polyuria-polydipsia syndrome revealing diabetes mellitus. This case
      illustrates the possibility for a partial epilepsy to occur in relation with a
      nonketotic hyperglycemia. If in most of those cases there is no underlying
      cortical lesion, in some observations the hyperglycemia is associated with an
      infarction. In our case the MRI revealed another type of lesion: a cortical
      dysplasia in form of a unilateral micropolygyria with a perisylvian distribution
      centered around the insula. The discovery of a cortical dysplasia at such an age
      is very unusual.

PMID- 11458190
TI  - [Acute onset syringomyelia: two cases].
AB  - Two cases of acute presentation of cervical syringomyelia associated with Chiari
      malformation are reported. In the first case, dysphagia was the main symptom; the
      second patient had symptoms suggesting acute brain stem ischemia. The mechanism
      of this acute onset of the illness is discussed.

PMID- 11458191
TI  - [Bartonella henselae meningoencephalitis].

PMID- 11458192
TI  - [Medical treatment of trauma-induced coma].

PMID- 11458193
TI  - [Two confusion scales].

PMID- 11458194
TI  - [Guidelines of the consensus conference on multiple sclerosis].

PMID- 11458196
TI  - From the Art Director's Desk.

PMID- 11458195
TI  - Editorial.

PMID- 11458197
TI  - The pineal gland as a central regulator of cytokine network.
AB  - Even though cytokines may fundamentally act as local factors, the recent advances
      in the knowledge of neuroimmunomodulation (NIM) would suggest the existence of a
      central regulation of their secretion and activity. Several neuroactive
      substances have appeared to influence cytokine secretion, and on the other hand
      cytokines may modulate the neuroendocrine functions. However, at present only for
      the pineal gland, whose fundamental NIM role is well known, it is possible to
      recognize reciprocal influences between cytokine action and pineal endocrine
      activity, suggesting the existence of feedback mechanisms responsible for a
      central regulation of cytokine network. Melatonin (MLT), which is the most
      investigated pineal immunomodulating hormone, may stimulate IL-2 release by T
      helper-1 (TH-1) lymphocytes and that of IL-12 by dendritic cells (DC), whereas
      both IL-2 and IL-12 would inhibit MLT release. The physiological significance of
      IL-2-IL-12-MLT interactions would be the maintenance of an effective TH-1
      dependent cellular immunity, including the anticancer immune response. A third
      possible pineal-cytokine feedback mechanism involves tumor necrosis factor-alpha
      (TNF-alpha) secretion, with a stimulatory effect of TNF-alpha on MLT release and
      an inhibitory one of MLT on TNF-alpha production. This finding would explain the
      anti-cachectic property of MLT itself. A further knowledge of pineal-cytokine
      interactions, as well as of other endocrine-immune circuits, will allow a better
      definition of the physiopathology of human chronic immunoinflammatory diseases,
      whose clinical course has appeared to be influenced by psychoemotional factors.

PMID- 11458198
TI  - The role of metals in autoimmunity and the link to neuroendocrinology.
AB  - Current available literature indicates a risk for metal-induced autoimmunity in
      man. Metal pathology may be due to toxic or allergic mechanisms where both may
      play a role. The main factors decisive for disease induced by metals are exposure
      and genetics which determine the individual detoxifying capacity and sensitivity
      to metals. This paper reviews the possible mechanisms which may play a role in
      metal-induced autoimmunity with the emphasis on multiple sclerosis (MS),
      rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). We also
      discuss the role of inflammation-induced changes in the hypothalamus-pituitary
      adrenal (HPA) axis as a possible explanation of fatigue, depression and other
      psychosomatic symptoms observed in these diseases. The increased knowledge about
      individual sensitivity based on genotype and phenotype variability together with
      the use of biomarkers for the diagnosis of this individual susceptibility seems
      to be the key in elucidation of the operating mechanisms. Since metal-induced
      sensitization may be induced by chronic low-dose exposure, the conventional
      toxicological approach comparing concentrations of metals in brain autopsies,
      organ biopsies and body fluids in patients and controls may not provide answers
      regarding the metal-pathology connection. To address this issue, longitudinal
      studies of metal-sensitive patients are preferable to the traditional case
      control studies.

PMID- 11458199
TI  - Expression of NADPH-diaphorase (NOS) in rat hypothalamo-neurohypophysial system
      after ischemic and traumatic brain injury.
AB  - To investigate the sites of nitric oxide synthase (NOS) expression after brain
      injury, NADPH-d histochemistry was performed on the hypothalamo-neurohypophysial
      system (HNS) of adult rats several days after both ischemia and trauma. Electron
      microscopic examination revealed the sites of formazan end-product of the
      diaphorase reaction in some neurons, astrocytes, cells and vascular pericytes,
      and in all activated microglial/macrophagal cells in perivascular and
      juxtaneuronal regions of hypothalamus. In neurohypophysis, positive NADPH-d
      staining was present in cytosol of many pituicytes, endothelial cells, pericytes
      and corresponding axonal endings. NADPH-d activity was also present in
      perivascular macrophages or microglial cells of neurohypophysis. Finally, we
      suppose that NOS expression and the consequent productions of nitric oxide could
      be involved in pathophysiology of HNS injury by ischemia and trauma, where
      activations inducible isoform of NOS especially, may contribute to a variety of
      neurogenerative processes. The imbalance in regulation of nitric oxide could
      disturb the physiological function of this neuroendocrine system.

PMID- 11458200
TI  - Hypoxia induces oxytocin release in the rat.
AB  - These studies were undertaken to investigate the impact of hypoxia on the release
      of oxytocin (OXT) at the median eminence (ME) in adult male rats, and the
      possible glucocorticoid involvement in modulating this release. Hypoxia was
      achieved in a hypobaric chamber. The results were as follows: (a) Acute hypoxic
      stress induced a release of OXT in ME proportional to its intensity and duration.
      (b) Chronic hypoxia (5-25 days) had no statistically significant influence on the
      ME level of OXT. (c) After bilateral adrenalectomy (ADX), the levels of OXT in ME
      were decreased, and there were no further significant changes in these levels
      when the rats were exposed to hypoxia. (d) The decrease of OXT in ME of ADX rats
      was partly reversed by replacement with dexamethasone (DEX, i.p. 500 &mgr;g/rat).
      These results suggest that acute hypoxia produces an intensity- and duration
      dependent release of OXT and that such release may be modulated in part by
      hypoxia-activated high circulating glucocorticoids and their negative feedback on
      the release of corticotropin releasing hormone (CRH).

PMID- 11458201
TI  - Congress Report: International Congress of Neuroimmunomodulation, ISNIM-99.

PMID- 11458202
TI  - Interaction between central effects of ethanol and melatonin in mice.
AB  - Effects of melatonin on acute toxicity of ethanol and ethanol-induced
      hypothermia, ethanol and thiopental sleeping time and ethanol-induced
      hypermotility were investigated in mice. The melatonin (1 and 5 mg/kg) was
      injected i.p. in single or repeated doses (7 days). The experiments were
      performed during the light phase of the light/dark cycle. It has been shown that
      a single dose of melatonin shortened duration of ethanol sleep and decreased
      ethanol-induced hyperactivity in mice. Melatonin given to mice for 7 days did not
      influence ethanol-induced effects. Melatonin prolonged thiopental hypnotic
      effect. The results of central interaction of ethanol and melatonin may be of
      antagonistic or synergistic nature.

PMID- 11458203
TI  - Effects of neuropeptide Y (NPY), galanin and vasoactive intestinal peptide (VIP)
      on pituitary hormone release and on ovarian steroidogenesis.
AB  - Ovarian folliculogenesis is regulated by the gonadotrophins, but in recent years
      other peptides have been found to serve as local regulators of ovarian function.
      The aim of this study is to evaluate the effects of NPY, galanin and VIP on
      pituitary and gonadal hormone release. Effects of NPY, galanin and VIP on
      progesterone, estradiol production by cultured rat granulosa and effects of these
      peptides on pituitary hormone release by cultured pituitary cells were examined
      according to methods previously described. Maximal effects of NPY, galanin and
      VIP on pituitary hormone release and on gonadal steroids were observed after
      administration of 10 nM of these peptides during 60 mins incubation. VIP and NPY,
      but not galanin, stimulated PRL release from cultured pituitary cells. VIP
      increased also LH release whenever NPY and galanin did not change LH release from
      pituitary cells. Galanin, but not NPY and VIP, leads to an increase of GH
      production. VIP, NPY and galanin did not change TSH and FSH release. NPY, galanin
      and VIP markedly stimulated progesterone release from cultured granulosa cells.
      NPY, galanin and VIP did not change estradiol and testosterone release.
      Conclusions. Direct effects of NPY, galanin and VIP on pituitary hormone release
      may indicate their role in the mechanism of pituitary hormone release. A marked
      increase of progesterone from cultured granulosa cells after VIP, NPY and galanin
      suggests that these peptides may be involved in the local ovarian
      steroidogenesis.

PMID- 11458204
TI  - The age-related quantitative ultrastructural changes in pinealocytes of gerbils.
AB  - OBJECTIVES. Relatively few ultrastructural studies of the pineal gland of aging
      animals have been published. The pineal gland of the gerbil is especially
      interesting in respect to aging because of its progressive calcification with
      age, and this species has been considered as an excellent model for research on
      aging. Therefore, the aim of the present study was to examine the quantitative
      ultrastructure of pinealocytes of the gerbil in three different age groups.
      METHODS. Three groups of animals were included in the study: 1-month-old, 3-month
      old, and 14-month-old. Cross-sectional areas of the pinealocyte and its nucleus
      and relative volumes of the following cell organelles: mitochondria, lysosomes,
      Golgi apparatus, granular endoplasmic reticulum and calcareous concretions as
      well as the number of dense-core vesicles and "synaptic" ribbons were analyzed.
      RESULTS. No age-dependent changes were observed in the size of pinealocytes and
      their nuclei. The relative volume of mitochondria and the number of dense-core
      vesicles increased progressively with age, and that of lysosomes was lowest in
      the 1-month-old animals and increased at age of 3 and 14 months, whereas a
      decrease in the relative volume of granular endoplasmic reticulum was observed in
      3- and 14-month-old gerbils in comparison with 1-month-old animals. No difference
      was observed in relative volume of Golgi apparatus and in the number of
      "synaptic" ribbons. The most striking change was observed in the formation of
      calcareous concretion within the pineal with age. The pineal gland of 1-month-old
      gerbils was essentially devoid of these structures, their number and size in 3
      month-old animals were moderate, and increased dramatically in 14-month-old
      animals. CONCLUSION. The ultrastructural features of the gerbil pinealocyte in
      all examined age groups point to high metabolic activity of these cells.

PMID- 11458205
TI  - Concentration of neuropeptide Y, galanin, &bgr;-endorphin, vasoactive intestinal
      peptide and gonadotropin releasing hormone in the hypothalamus of gilts during
      the estrous cycle.
AB  - Numerous reports indicate that peptides isolated from the brain such as beta
      endorphin (beta-END), neuropeptide Y (NPY), galanin (GAL) or vasoactive
      intestinal peptide (VIP), modulate secretion of gonadotropins and prolactin. The
      objective of the present experiment was to determine concentrations of NPY, GAL,
      beta-END, VIP and GnRH in the preoptic area (POA), medial basal hypothalamus
      (MBH) and pituitary stalk-median eminence (SME) during the estrous cycle in the
      pig. Gilts were slaughtered on Days 5, 10, 15 and 20 of the estrous cycle. Blood
      samples for analyses of progesterone were taken before slaughter. Neuropeptide
      concentrations in brain tissues were determined using RIA. The highest
      concentrations of all determined peptides occurred in SME. GnRH concentration in
      MBH was lower (p<0.05) in POA and SME on Day 20 than on Day 5. NPY concentration
      in POA was 5-6 times greater (p<0.05) on Days 10 and 20 than on Day 5. Similarly,
      concentrations of VIP in POA were greater (p<0.05) on Day 10, Day 15 and Day 20
      than on Day 5. The concentration of GAL in POA was higher on Days 10 and 15
      (p<0.05) than on Days 5 and 20. The concentration of GAL in SME was lowest on Day
      5 and then significantly increased on Days 10, 15 and 20. In SME, concentration
      of beta-END increased 10 times on Days 15 and 20 when compared to Day 5 of the
      cycle. The correlation between concentration of GAL in the POA and MBH and
      progesterone concentration in the peripheral blood was positive, whereas this
      correlation associated with the SME was negative. These results indicate that
      considerable changes in various neuropeptide concentrations in different areas of
      the porcine hypothalamus are associated with stage of the estrous cycle and that
      GAL may be involved in control of the preovulatory LH surge in pigs.

PMID- 11458206
TI  - Human papillomavirus infection and survival in oral squamous cell cancer: a
      population-based study.
AB  - OBJECTIVE: To determine whether human papillomavirus (HPV) type 16 affects
      survival in oral squamous cell carcinoma. STUDY DESIGN: Two hundred fifty-four
      patients diagnosed with primary oral cancer were studied for survival in relation
      to tumor HPV type 16 status. Kaplan-Meier analysis and Cox proportional hazard
      models were used to assess survival and estimate hazard ratios adjusted for
      potential confounders. RESULTS: HPV type 16 DNA was detected in 15.1% of tumors.
      HPV 16 positive patients had significantly reduced all-cause mortality (hazard
      ratio [HR] estimates = 0.34, 95% CI = 0.14, 0.83) and disease-specific mortality
      (HR = 0.17, 95% CI = 0.04, 0.76) compared with HPV 16 negative patients after
      adjustment for age, stage, treatment, smoking, alcohol, education, and comorbid
      disease. CONCLUSIONS: The presence of HPV type 16 DNA is independently associated
      with a favorable prognosis in patients with oral squamous cell carcinoma.
      CLINICAL SIGNIFICANCE: Although HPV genotyping is currently not widely available,
      it may provide important prognostic information.

PMID- 11458207
TI  - Free flap reconstruction of the head and neck: analysis of 241 cases.
AB  - OBJECTIVE: We undertook this study of free flap reconstruction of the head and
      neck to stratify patients and procedures, to determine how donor site preference
      changed over time, to assess medical and surgical outcomes, and to identify
      variables associated with complications. METHODS: We analyzed computerized
      medical records from 236 patients who underwent a total of 241 reconstructions at
      a tertiary academic medical center in St. Louis between 1989 and 1998. We created
      a more detailed retrospective database of 141 of those patients by using 48
      perioperative variables and 7 adverse outcome measures. Multivariate statistical
      models were used to analyze associations between variables and outcomes. RESULTS:
      The fibula became the preferred donor site for mandibular reconstruction, and the
      radial forearm became the preferred donor site for pharyngoesophageal
      reconstruction. For the 241 procedures, the mortality rate was 2.1%, the median
      length of stay was 11 days, and the flap survival rate was 95%. Administration of
      more than 7 L of crystalloid during surgery and age over 55 were associated with
      major medical complications. Blood transfusion, prognostic comorbidity, and
      number of surgeons correlated with length of stay. Cigarette smoking and receipt
      of more than 7 L of crystalloid during surgery were associated with overall flap
      complications, and weight loss of more than 10% before surgery, more than one
      operating surgeon, and cigarette smoking were associated with major flap
      complications. CONCLUSIONS: Risk to patients and transferred tissue is low in
      free flap head and neck reconstruction. Age, smoking history, and weight loss
      should be considered during patient selection. Fluid balance should be considered
      during and after surgery. Division of labor for patient care should be carefully
      delineated among surgeons in a teaching setting.

PMID- 11458208
TI  - Progression difference between cancers of the larynx and hypopharynx is not due
      to tumor size and vascularization.
AB  - A recent survey of head and neck cancer indicated a sharp difference in survival
      between cancer of the hypopharynx and cancers formed in other head and neck
      sites. We have analyzed tumor size relative to clinical stage and vascularization
      as possible causes for such a difference in a series of 21 patients with cancer
      of the laryngopharynx (11 glottic and 10 hypopharyngeal). We found that the
      volume of the smallest cancers of the larynx at stage 2 is significantly larger
      than the volume of the cancers of the hypopharynx at stage 4 (P < 0.05). Next, we
      have determined by immunohistochemistry and morphometry the microvessel density,
      microvessel perimeter, and vascular endothelial growth factor (VEGF) expression
      of laryngo-hypopharyngeal cancers. Analysis of these data indicates that there is
      no difference in vascularization and VEGF expression between these two tumor
      types. These data strongly suggest that the invasive but not the angiogenic
      phenotype of hypopharyngeal cancer cells could be responsible for the more
      aggressive biologic behavior of this head and neck cancer subtype.

PMID- 11458209
TI  - Elective neck dissection versus observation in stage I squamous cell carcinomas
      of the tongue and floor of the mouth.
AB  - A retrospective study was undertaken of patients with T1N0M0 squamous cell
      carcinoma of the oral tongue and floor of the mouth who underwent surgical
      treatment between 1985 and 1995. Evaluation of two groups of patients (neck
      dissection versus observation) was made according to the management of the neck.
      Results were obtained regarding the presence of occult metastases, recurrence in
      the neck, treatment failure, results of salvage treatment, and disease-free
      survival. Forty-nine patients underwent surgical treatment: 25 resection of
      primary and 24 resection plus neck dissection. Overall incidence of regional
      metastases was 24.5%. Eight patients (16%) developed recurrence of the disease.
      Seven (14%) had regional recurrences (including 1 with distant metastases) and
      1(2%) had local recurrence. Twenty-four percent of patients from the resection of
      primary group developed neck recurrences in comparison with 4% of the resection
      plus neck dissection group (P = 0.05). Overall salvage rate was 37.5%. Second
      primary tumors developed in 16% of patients. Patients who underwent elective neck
      dissection had a 23% higher disease-free survival rate compared with those who
      underwent resection of the tumor alone (P = 0.03). The findings of this study
      stress the importance of control of the neck in early oral cancer. Elective neck
      dissection significantly improved regional control of the disease.

PMID- 11458210
TI  - Thyroid surgery: a comparison of outcomes between experts and surgeons in
      training.
AB  - OBJECTIVES: Our objective was to compare the results of thyroid surgery performed
      by residents in a large metropolitan public hospital (MPH) with those performed
      by faculty in a large private hospital (PH) setting. METHODS: All records of
      thyroid surgery performed by otolaryngologists for the period between 1986 and
      1998 were reviewed. Inclusion criteria were adequacy of data and follow-up.
      Ninety-two thyroid procedures performed by residents in an MPH were compared with
      181 thyroid operations in a PH setting performed by the faculty of these
      residents for differences in accuracy of diagnostic studies, operative
      parameters, and complication rates. RESULTS: The demographic distribution in both
      groups was similar. Presenting symptoms were twice as frequent in the MPH group
      (45% vs 22%). More total thyroidectomies were performed in the PH group (49% vs
      32%). Blood loss, operative time, and hospitalization days were similar in both
      groups. Preoperative fine needle aspiration and intraoperative frozen section
      results showed sensitivities and specificities that were comparable. No permanent
      vocal cord paralysis was observed in either group. Permanent hypocalcemia was
      more frequent in the PH group (8.8%:PH vs 5.1%:MPH). CONCLUSIONS: The results of
      thyroid surgery performed by residents in training in an Otolaryngology-Head &
      Neck Surgery program in an MPH, measured by rates of complications, length of
      hospitalization, and duration of surgery, are similar to those of faculty at a PH
      setting in groups of patients with very similar characteristics.

PMID- 11458211
TI  - Muscle fiber and satellite cell apoptosis in the aging human thyroarytenoid
      muscle: a stereological study with confocal laser scanning microscopy.
AB  - OBJECTIVE: This study determines the role of changes in numerical densities of
      apoptotic myonuclei and satellite cells in age-related remodeling of the
      thyroarytenoid muscle (TA). DESIGN: Changes in numerical densities of apoptotic
      myonuclei and satellite cells were estimated for the entire TA by using
      stereological techniques. RESULTS: There was an increase in N(V apoptotic
      myonucleus, fiber type) (P < 0.05) and in the percentage of apoptotic myonuclei
      (P < 0.05) in type 1 but not in type 2 muscle fibers. There was also an increase
      in N(V apoptotic satellite cell, fiber type) (P < 0.05) and in the percentage of
      apoptotic satellite cells (P < 0.05) in type 1 fibers but not in type 2 fibers.
      CONCLUSION: Apoptosis may contribute to age-related fiber loss and atrophy in the
      TA. SIGNIFICANCE: Therapeutic techniques based on decreasing the frequency of
      apoptosis may block age-related fiber loss and atrophy in the TA.

PMID- 11458212
TI  - Prospective analysis of sinus symptoms and correlation with paranasal computed
      tomography scan.
AB  - OBJECTIVES: We designed a prospective study to determine whether there is a
      correlation between the severity of sinus symptoms and the severity of computed
      tomography (CT) scan evidence of rhinosinusitis. METHODS: Acute and chronic
      rhinosinusitis patients rated their symptoms and had a CT scan of the sinuses
      taken the same day. A Likert severity scale and standardized CT scoring system
      were used. Data were analyzed by nonparametric methods with Kendall's rank
      correlation coefficient. RESULTS: The severity of 5 symptoms correlated with
      severity of disease on CT scan. Headache and facial pain or pressure had no
      correlation. CONCLUSION: The certainty of a clinical diagnosis of rhinosinusitis
      requiring treatment is enhanced in patients with high symptom severity scores for
      fatigue, sleep disturbance, nasal discharge, nasal blockage, or decreased sense
      of smell. Isolated headache and facial pain or pressure are less reliable
      predictors of CT scan findings supporting the diagnosis rhinosinusitis.

PMID- 11458213
TI  - Nasal irrigation for the alleviation of sinonasal symptoms.
AB  - OBJECTIVE: To determine the effect of nasal irrigation on sinonasal symptoms.
      STUDY DESIGN AND SETTING: A total of 150 adult subjects with chronic sinusitis
      symptoms were recruited from the community and assigned to 1 of 3 treatment
      groups: nasal irrigation with bulb syringe, nasal irrigation with nasal
      irrigation pot, or control treatment with reflexology massage. Groups 1 and 2
      performed daily hypertonic saline irrigation with 1 device for 2 weeks and then
      with the other device for 2 weeks. Group 3 performed reflexology massage daily
      for 2 weeks. Prospective data collected included pretreatment Medical Outcomes
      Study Short Form, pretreatment and posttreatment Rhinosinusitis Outcomes Measure,
      daily medication use, subjective treatment efficacy, and preference of irrigation
      method. RESULTS: There was a significant and equivalent improvement in
      Rhinosinusitis Outcomes Measure 31 score after 2 weeks of intervention in each
      treatment group; 35% of subjects reported decreased use of sinus medication.
      CONCLUSION: Daily nasal irrigation using either a bulb syringe, nasal irrigation
      pot, and daily reflexology massage were equally efficacious and resulted in
      improvement in the symptoms of chronic sinusitis in over 70% of subjects.
      Medication usage was decreased in approximately one third of participants
      regardless of intervention.

PMID- 11458214
TI  - Aggressive endoscopic resection of inverted papilloma: an update.
AB  - OBJECTIVE: Endoscopic resection has been proposed for sinonasal inverted
      papilloma (IP). Our objective was to determine the efficacy of aggressive
      endoscopic resection of IP. METHODS: Retrospective analysis was performed on
      patients undergoing endoscopic resection of IP at the University of Virginia
      between 1990 and 1996. Total ethmoidectomies, wide maxillary antrostomies,
      frontal recess explorations, sphenoidotomies, and turbinate resection were
      performed as required. Once all visible papilloma was removed, residual mucosa
      was removed by using a diamond burr to polish bone at the site of origin.
      RESULTS: Twenty-one patients were treated with endoscopic resection of IP. Only 1
      of 21 patients had an adjunctive external procedure (an osteoplastic flap without
      obliteration). Average follow-up was 41.9 months after initial aggressive
      endoscopic resection at the ureterovesical angle. Recurrences occurred in 19%
      (4/21) of patients. One of the 4 had two recurrences. Recurrences occurred in 16
      months or less, except for one noted at 35 months and another at 56 months.
      CONCLUSIONS: Aggressive endoscopic resection of IP by experienced rhinologists is
      an acceptable treatment.

PMID- 11458215
TI  - The effects of sensitization and hypersensitivity reaction on transepithelial
      antigen transport of rat nasal mucosa.
AB  - METHODS: The prevalence of airway allergy is very high. The ways that antigen
      passes across the airway tract epithelial barrier are not well understood. This
      study uses a model antigen, horseradish peroxidase (HRP), to sensitize and
      challenge the respiratory tract in the rat model. RESULTS: The results showed
      increases in HRP endosomes in nasal epithelial cells 5 minutes after HRP
      challenge in the sensitized rats compared with controls, which were further
      increased 30 minutes after HRP challenge, as well as with the paracellular region
      filled with HRP products. Meanwhile, mast cells were activated as shown by
      degranulation. Analysis of cell type showed that there were many more HRP
      endosomes in the nonciliated cells and there were many more nonciliated cells in
      the nasal mucosa of the sensitized rats. CONCLUSION: The results demonstrate that
      sensitization promotes airway mucosal epithelial cells' uptake and transport of
      specific antigen and that mast cells may play certain roles in this process.

PMID- 11458216
TI  - Clinical anatomy of the nasal process of the frontal bone (spina nasalis
      interna).
AB  - OBJECTIVES: During endonasal frontal sinusotomy with the sharp spoon, a solid
      piece of bone is frequently encountered anterior to the neo-ostium. This bone may
      be referred to as the nasal process of the frontal bone or internal nasal spine
      (spina nasalis interna). A prominent spina may render an extended sinusotomy
      difficult and may call for use of the drill. A series of anatomic measurements is
      presented to illustrate the 3-dimensional anatomy of the spina nasalis and the
      regional anatomy. METHODS: A maximum endonasal frontal sinusotomy (Draf type I-II
      procedure, nasofrontal approach type II) was performed on 36 anatomic specimens
      by means of a sharp spoon. The dimensions of the remaining nasal spine were
      measured subsequently together with the anterior-posterior diameter of the
      inferior frontal sinus, the thickness of the anterior frontal sinus wall, and the
      distance from the neo-ostium to the anterior ethmoidal artery. RESULTS: The
      individual microanatomy of the medial floor of the frontal sinus showed a wide
      range of variation. The average height of the individual spine was 10 mm, the
      maximum depth 6 mm. A correlation was found between the nasofrontal angle of the
      specimen and the anterior-posterior dimension of the spine: the more acute the
      angle, the thicker the spine. In three quarters of the cases, the neo-ostium was
      separated by just one anterior ethmoidal cell from the anterior ethmoidal artery.
      CONCLUSIONS: The presented investigations provide the surgeon with quantitative
      data on the individual anatomy of the nasal spine and offer additional
      information for selecting the appropriate surgical procedure in the individual
      patient.

PMID- 11458217
TI  - Conservative management of infections in cochlear implant recipients.
AB  - OBJECTIVE: The goal of this study was to evaluate a conservative management
      strategy of postoperative infection after cochlear implantation. METHODS: A
      retrospective review of the medical records of 108 cochlear implant patients
      operated on at the University of California, San Francisco between 1991 and 2000
      and 133 cochlear implant patients from the University of Iowa between 1997 and
      2000 showed 4 patients with evidence of postoperative infections. The clinical
      presentation, intervention, laboratory results, and outcome are analyzed in each
      case. RESULTS: Minimal surgical intervention with limited incision and drainage
      with prolonged postoperative antibiotics was effective in treating postoperative
      cochlear implant infections without the need for device removal. Implant function
      remained unaffected after surgery. CONCLUSION: Postoperative cochlear implant
      infections can be effectively controlled with limited surgical and prolonged
      medical management. Chronic implant infections may be explained by a primary
      immunodeficiency. With appropriate treatment leading to infection control, a
      conservative management strategy is advocated before consideration of device
      explantation.

PMID- 11458218
TI  - Chlorpromazine alters outer hair cell electromotility.
AB  - OBJECTIVE: Outer hair cells (OHCs) of the inner ear rapidly convert electrical
      gradients into mechanical force, enhancing cochlear sensitivity and frequency
      selectivity. We investigated the effect of chlorpromazine, an antipsychotic
      medication that alters membrane biomechanics, on OHC electromotility. STUDY
      DESIGN: Isolated guinea pig outer hair cells were perfused with chlorpromazine
      under whole-cell patch-pipette recording conditions. Electromotile responses were
      measured. RESULTS: A dramatic, reversible, dose-dependent depolarization of
      voltage at peak capacitance (V(pkCm)) was seen with chlorpromazine treatment. The
      gain of the electromotile response was maximal near V(pkCm) both before and after
      chlorpromazine application. Unlike the 3 other agents that alter electromotility
      (salicylate, lanthanides, membrane tension), chlorpromazine did not change peak
      capacitance (Cm(pk)), which varies directly with maximal electromotile gain.
      CONCLUSION: Chlorpromazine changes the membrane voltage at which OHCs exhibit
      maximal electromotile gain, without changing the magnitude of electromotile
      responses. SIGNIFICANCE: Chlorpromazine may diminish hearing thresholds or
      otoacoustic emissions in large doses.

PMID- 11458219
TI  - Management of facial paralysis resulting from temporal bone fractures: Our
      experience in 115 cases.
AB  - OBJECTIVE: The goal of this study was to review decision factors and overall
      results regarding surgical and nonsurgical management of post-traumatic facial
      nerve paralysis (FP). STUDY DESIGN: A retrospective study and literature review
      were performed. METHODS: Between 1984 and 1990, 115 cases of post-traumatic FP
      were handled. Patients were evaluated through clinical, audiologic, radiologic,
      and electromyogram assessment. Depending on examination results, patients were
      treated either medically or surgically through total facial nerve decompression.
      RESULTS: Forty-nine of the 50 medically treated patients experienced a normal or
      subnormal facial function recovery (grade I-II). Of the 65 (56.5%) surgically
      treated patients, 52 (80%) had immediate, 2 had delayed, and 11 (17%) had unknown
      delay-associated FP. The approaches chosen were middle fossa and transmastoid
      (75.3%), translabyrinthine (10.7%), or pure transmastoid according to facial
      nerve nonmotor branch evaluation, hearing, location of the fracture line, and the
      patient's general condition. Lesions were predominantly found in the geniculate
      ganglion area (66.2%). A nerve gap was found in only 13.8% of the cases. At 2
      years after surgery, 93.8% had a grade I to III recovery. None had grade V or VI.
      CONCLUSION: The rarity of severe nerve lesions encountered in surgically treated
      patients raises the question of better selection of candidates for surgery.
      Surgery is clearly indicated when FP is total, is of immediate onset, and is
      associated with a bad prognosis electromyogram pattern. In other settings,
      decisions are to be made based on high-resolution CT data and electromyogram
      results, thanks to a clinical survey and second electromyogram evaluation.

PMID- 11458220
TI  - Osseointegrated implants in children: experience from our first 100 patients.
AB  - This study was undertaken on 100 children aged 16 years or under intended for
      installation of osseointegrated implants. Of these, 76 had implants installed for
      bone-anchored hearing aids or prostheses. The main indication for implant
      installation was a bilateral ear malformation. Surgery was generally performed as
      a two-stage procedure with a healing time of 3 to 4 months in between. Available
      bone thickness was on average 2.5 mm, and lack of bone necessitated bone
      augmentation in 12 patients. Thirty-nine percent of implants were installed in
      contact with the dura, sigmoid sinus, or an air cell. Implant failures were 5.8%
      of 170 inserted fixtures. Adverse skin reactions appeared in 9.1% of patients
      over a 21-year follow-up period. Revision surgery was undertaken in 22% of
      patients because of appositional growth of the temporal bone. Of the 24 children
      considered but not found suitable for osseointegration surgery, plastic surgery
      was considered a better option, or growth of the temporal bone was awaited. It is
      concluded that the rate of implant failure is lower in children; the frequency of
      skin reactions is the same as in adults, but revision surgery is more common in
      young patients because of new bone formation. Our clinical experience supported
      by the data presented in this article suggests that the concept could be used
      with good functional and aesthetic results in children.

PMID- 11458221
TI  - Ear piercing for individuals with metal hypersensitivity.
AB  - OBJECTIVE: To describe and evaluate an ear piercing and earring retention method
      for individuals with metal hypersensitivity. SETTING: Private facial plastic
      surgery practice associated with a tertiary care medical center. METHODS: Thirty
      one patients with a history of hypersensitivity to metallic jewelry (62 ears)
      underwent earlobe piercing with an intravenous catheter. RESULTS: None of the
      patients experienced an infection or hypersensitivity reaction. All patients were
      able to wear nickel-free earrings for short periods without using the shortened
      catheter. CONCLUSION: Using the distal shaft of an intravenous catheter as an
      earring post sheath is a safe and effective technique that allows hypersensitive
      individuals to wear earrings in pierced ears on a limited basis.

PMID- 11458222
TI  - Metaplastic bone formation in nasal polyps with histologic presence of
      transforming growth factor beta-1 (TGFbeta-1) and bone morphogenetic proteins
      (BMPs).

PMID- 11458223
TI  - Chondrosarcoma of the nasal septum.

PMID- 11458224
TI  - Sphenoid sinusitis caused by Clostridium perfringens.
AB  - Anaerobic bacterial infections in chronic sinusitis are well described in
      literature. We present what is believed to be the first reported case of
      Clostridium perfringens presenting as the causative pathogen in paranasal
      sinusitis. This patient presented with severe headaches and, with CT and MRI
      findings of unilateral sphenoid sinus opacification, with bone demineralization
      and intrasinus calcification. This patient responded to endoscopic debridement
      and long-term antibiotics without sequelae.

PMID- 11458225
TI  - Disfiguring nasal metastasis from colorectal adenocarcinoma: a case report.

PMID- 11458226
TI  - Bronchogenic cyst of the oropharynx and hypopharynx in a neonate.

PMID- 11458227
TI  - Clear cell chondrosarcoma of the larynx.

PMID- 11458228
TI  - Angioleiomyoma of the auricle: a rare tumor.

PMID- 11458229
TI  - Acute mastoiditis with temporomandibular joint effusion.

PMID- 11458230
TI  - Immune-mediated sensorineural hearing loss in a patient with ankylosing
      spondylitis: a case report.

PMID- 11458231
TI  - Bilateral malformation of the internal auditory canal: Atresia and contralateral
      transverse megacrest.

PMID- 11458232
TI  - Using an endotracheal tube in difficult secondary tracheoesophageal puncture: a
      novel technique.

PMID- 11458233
TI  - Reactivated laryngeal coccidioidomycosis.

PMID- 11458234
TI  - Pleomorphic adenoma of the soft palate.

PMID- 11458235
TI  - Innovation or marketing ploy: How do we distinguish between the two?

PMID- 11458236
TI  - Periapical central giant cell granuloma.

PMID- 11458237
TI  - Nicorandil and oral ulceration.

PMID- 11458238
TI  - Paresthesia of the mental nerve.

PMID- 11458239
TI  - External root resorption of a primary molar: "incidental" histopathologic finding
      of clinical significance.

PMID- 11458240
TI  - Update on renal disease for the dental practitioner.

PMID- 11458241
TI  - Histologic evaluation of immediate versus delayed placement of implants after
      tooth extraction.
AB  - OBJECTIVE: Full osseointegration is necessary to achieve long-term success of
      dental implants. We aimed to find out the relative merits of immediate and
      delayed insertion of implants after dental extraction. STUDY DESIGN: We completed
      a histologic and histomorphometric examination of the tissue adjacent to delayed
      and immediate implants in 8 beagle dogs. In 4 dogs, implants were inserted
      immediately after the extraction of second premolars; in the remaining 4, the
      implants were inserted 6 months after the extraction. Fluorochrome bone markers
      were injected on 2 occasions before the dogs were killed 8 months after the
      implants had been inserted. Each implant and its surrounding tissue was examined
      macroscopically and microscopically. Both histologic dynamic and histologic
      static histomorphometry were used in this analysis. Statistical significance was
      tested by using the Student t test for paired and unpaired observations, the
      Dunnett t test, and Fisher's least significant difference method for multiple
      comparisons. RESULTS: The implants placed immediately had 76% of their surface
      covered with bone, whereas the implants placed after bony healing had 81% of
      their surface covered with bone. The fibrous tissue at the cervical end of the
      implant was more dense; the delayed implants also had a greater number of
      adhesive epithelial elements (hemidesmosomes). Use of dynamic and static
      histomorphometry revealed no significant differences between the 2 groups.
      CONCLUSION: We found new soft and hard tissue around dental implants 8 months
      after their insertion in both groups. Pseudoankylotic healing was seen in the
      osseous part. The lower level of osseointegration in the immediately placed
      implants was attributable to the early resorption of bone in the crestal part,
      resulting in a larger part of the implant being surrounded by soft tissue.

PMID- 11458242
TI  - Comparative radiologic study of bone density and cortical thickness of donor bone
      used in mandibular reconstruction.
AB  - OBJECTIVE: The aim of this study was to compare the total cancellous bone
      density, bone-implant interface density, and cortical thickness of 6 donor bone
      types commonly used in oral and maxillofacial reconstruction. METHODS: A total of
      120 bones from 20 Korean adults-including iliac bones, fibulas, cranial bones,
      scapulas, ribs, and clavicles-were selected. The implant recipient site was
      determined by the shape, contour, and anatomical limitations of the bones. The
      serial cross-sectional images of each bone were then acquired through computed
      tomography. Total cancellous bone density, bone-implant interface density around
      the imaginary implant fixture, and the cortical thickness along both sides of the
      imaginary fixture on each cross-sectional image were evaluated and compared.
      RESULTS: The cancellous bone density of each donor bone type had a statistically
      significant difference. The cranial bone showed the highest cancellous bone
      density, followed by the iliac bone, clavicle, scapula, rib, and fibula (P <.05).
      The bone-implant interface density of the cranial bone, clavicle, fibula, and
      scapula each belonged to the same Duncan's group, whereas the rib and iliac bone
      showed lower bone-implant interface density. In average cortical thickness, the
      scapula and fibula had a thicker cortex surrounding the imaginary implant than
      the other bones, and the rib had the thinnest cortex. CONCLUSION: Although more
      extensive testing is needed to explain the clinical implications of these
      results, the findings of this study may help clinicians choose the most
      appropriate donor bone.

PMID- 11458243
TI  - Principles of computer-assisted arthroscopy of the temporomandibular joint with
      optoelectronic tracking technology.
AB  - PURPOSE: This preliminary clinical study evaluated the applicability, accuracy,
      and benefits of computer-assisted arthroscopy of the temporomandibular joint
      (TMJ) with optoelectronic tracking technology. MATERIALS AND METHODS: A hybrid of
      reality and virtual reality is built as a composite-reality environment by
      extracting 3-dimensional anatomical structures through use of computed
      tomography, magnetic resonance imaging, radiography, and other types of imaging
      procedures commonly used in clinical praxis. These various independent sources of
      imaging data of a particular patient can be combined with and complemented by
      complex graphic simulations. Intraoperatively they are merged with online
      position data of surgical instruments inside the patient's TMJ. This hybrid model
      of detailed anatomical structures, guidelines, and real-time instrument positions
      allows the surgeon to accurately plan the arthroscopic intervention as well as to
      navigate effectively intraoperatively. RESULTS: In the first 10 cases of computer
      assisted TMJ arthroscopy, composite reality environment technology permitted the
      online visualization of TMJ structures, puncture sites, instrument positions, and
      virtual pathways in relation to anatomical landmarks with high spatial accuracy
      (minimum, 0.0 mm; maximum, 2.5 mm; mean, 1.4 mm; SD, 0.6 mm) and high temporal
      resolution (100 ms). Past, present, and possible future instrument positions can
      be displayed. The application of computer-assisted arthroscopy caused little
      immobility for either surgeon or patient. CONCLUSION: Even experienced surgeons
      profit from improved precision in the handling of the arthroscope; thus this
      technology was found to be particularly useful in degenerative temporomandibular
      disorders and for triangulation procedures.

PMID- 11458244
TI  - Syndromes with salivary dysfunction predispose to tooth wear: Case reports of
      congenital dysfunction of major salivary glands, Prader-Willi, congenital
      rubella, and Sjogren's syndromes.
AB  - Four cases-of congenital dysfunction of the major salivary glands as well as of
      Prader-Willi, congenital rubella, and Sjogren's syndromes-were identified in a
      series of 500 patients referred for excessive tooth wear. Although there was
      evidence of consumption of highly acidic drinks, some occlusal parafunction, and
      unacceptable toothbrushing habits, salivary dysfunction was the salient factor
      predisposing a patient to tooth wear in these syndromal cases. The 500 subjects
      have been characterized either as having medical conditions and medications that
      predispose them to xerostomia or lifestyles in which workplace- and sports
      related dehydration lead to reduced salivary flow. Normal salivation, by
      buffering capacity, clearance by swallowing, pellicle formation, and capacity for
      remineralization of demineralized enamel, protects the teeth from extrinsic and
      intrinsic acids that initiate dental erosion. Thus, the syndromes, unrelated in
      many respects, underline the importance of normal salivation in the protection of
      teeth against tooth wear by erosion, attrition, and abrasion.

PMID- 11458245
TI  - Sequelae and complications related to dental extractions in patients with
      hematologic malignancies and the impact on medical outcome.
AB  - OBJECTIVE: The purpose of this retrospective study was to evaluate sequelae and
      complications after dental extractions and to analyze their impact on medical
      treatment in patients with myelodysplastic syndrome, acute and chronic leukemia,
      and multiple myeloma during a 3-year period. STUDY DESIGN: The study population
      included 388 patients with hematologic malignancies. All medical and dental
      charts were reviewed in a retrospective fashion to identify patients who received
      dental extractions. Preexisting dental disease and intervention (extraction) were
      evaluated, and parameters such as days of hospitalization and survival rate were
      compared with those of the remainder population who did not receive dental
      extractions. RESULTS: Of the 388 patients, 69 underwent dental extractions and 9
      had sequelae and complications after the intervention. The resulting complication
      rate of 13% was reported. Although some patients did experience delay of
      chemotherapy or bone marrow transplant (BMT), or both, no significant difference
      was found in the number of days in the hospital for BMT and the survival rate for
      the patients with sequelae and complications (n = 9) and for the remainder
      population (n = 319) ( >.05). CONCLUSION: Dental extraction intervention provided
      in the prechemotherapy and pre-BMT time frame did not have a negative bearing on
      medical outcome.

PMID- 11458246
TI  - Prevalence of HIV-1 and oral lesions in pregnant women in rural Malawi.
AB  - OBJECTIVE: Whether oral lesions were associated with human immunodeficiency virus
      type 1 (HIV-1) status in a cohort of pregnant Malawian women was studied. STUDY
      DESIGN: Six hundred thirty-eight women participated in a randomized prospective
      study at 3 prenatal clinics in a rural area of southern Malawi. Oral
      examinations, followed by collection of oral fluid specimens with an HIV-1 oral
      specimen collection device, were performed. The specimens were tested for
      antibodies against HIV-1. RESULTS: Sixty-one oral lesions were found in 60
      participants. While traditional HIV-1 associated lesions were rare, benign
      migratory glossitis was unexpectedly common (6%). Oral hairy leukoplakia was
      significantly more common among women who were HIV-1 positive than among women
      who were HIV-1 negative. An HIV-1 prevalence rate of 21.8% was estimated among
      the women, with the highest rate of HIV-1 infection (34.1%) among women aged 25
      to 29 years. CONCLUSION: Stratifying lesions showed a small number of oral hairy
      leukoplakia to be markers for HIV-1. A high seroprevalence was found in this
      rural cohort, but there were unexpectedly few oral lesions. The relatively few
      oral lesions diagnosed may indicate a recent infection with HIV.

PMID- 11458247
TI  - A comparison of salivary calprotectin levels in subjects with and without oral
      candidiasis.
AB  - OBJECTIVES: The purpose of this study was to compare salivary calprotectin levels
      in subjects with oral candidiasis to the levels in healthy age- and sex-matched
      control subjects and to investigate the relationship of salivary calprotectin to
      intensity of oral candidal carriage and infection and to predisposing factors for
      candidiasis. STUDY DESIGN: Using enzyme-linked immunosorbent assay, we measured
      calprotectin in unstimulated whole saliva collected from 22 subjects with oral
      candidiasis and in saliva collected from 22 control subjects. Calprotectin levels
      in the 2 groups were compared by using the Wilcoxon signed rank test. The
      relationships between calprotectin levels and Candida counts were assessed by
      using the Spearman rank correlation test. The nonparametric 1-way analysis of
      variance test was used to study the relationship between calprotectin levels and
      presence of non-albicans Candida and individual predisposing factors for
      candidiasis. The Kruskal-Wallis test was used to evaluate the relationship
      between calprotectin and predisposing factors in subjects grouped by total number
      of predisposing factors identified. RESULTS: No relationship was found between
      calprotectin and individual or total number of predisposing factors. Higher
      calprotectin levels were found in subjects with candidiasis, and calprotectin
      concentration positively correlated with intensity of candidal infection.
      CONCLUSIONS: These findings suggest that calprotectin production, or release, or
      both, may be increased in subjects with candidiasis.

PMID- 11458248
TI  - Ductal papillomas of salivary gland origin: A report of 19 cases and a review of
      the literature.
AB  - The term ductal papilloma is used to identify a group of 3 rare benign papillary
      salivary gland tumors known as inverted ductal papilloma, sialadenoma
      papilliferum, and intraductal papilloma. They represent adenomas with unique
      papillary features and arise from the salivary gland duct system. We describe the
      clinical and microscopic features of 19 new cases of ductal papillomas and
      combine them with 116 cases previously published in the English-language medical
      literature. These 19 cases were composed of 13 inverted ductal papillomas, 3
      sialadenoma papilliferums, and 3 intraductal papillomas. Collectively, these 19
      ductal papillomas occurred most commonly in the sixth to eighth decade of life,
      with an average patient age of 54 years. Men predominated 1.37:1. The sialadenoma
      papilliferums presented as papillary lesions clinically with all 3 misinterpreted
      as squamous papillomas by the surgeons. The inverted ductal papillomas and
      intraductal papillomas appeared as submucosal nodules. The lip and the palate
      were the most common locations for inverted ductal papilloma and sialadenoma
      papilliferum, respectively. The sites for the 3 intraductal papillomas were the
      parotid papilla of the Stensen's duct, the upper lip, and the buccal mucosa. With
      light microscopy, inverted ductal papillomas appeared to arise from the excretory
      ducts near the mucosal surface, whereas intraductal papillomas appeared to arise
      from the excretory ducts at a deeper level. Sialadenoma papilliferum had a more
      complex histology, with a biphasic growth pattern of exophytic papillary and
      endophytic components. All 19 cases were treated by surgical excision. Follow-up
      information was available in only 2 cases, both inverted ductal papillomas.
      Neither case recurred during a 20-year period. Sialadenoma papilliferum, with a
      literature-derived recurrence rate of 10% to 15%, seems to assert a more
      significant biological behavior than inverted ductal papilloma and intraductal
      papilloma. Our findings justify the separation of these 3 entities based on
      clinical and histologic parameters. They are tumors of adulthood and, in
      addition, have in common their relationship to the excretory duct system, their
      anatomical distribution, and their general behavior.

PMID- 11458249
TI  - Ultrastructural aspects of connective tissue in hereditary gingival fibromatosis.
AB  - OBJECTIVE: The purpose of this study was to analyze the ultrastructure of
      gingival connective tissue from patients in one family affected by hereditary
      gingival fibromatosis (HGF). STUDY DESIGN: Electron microscopic examination was
      performed with gingival tissue from 10 patients from a Brazilian family with 132
      members. Fifty of 96 persons at risk for this disorder were affected, which is
      consistent with an autosomal dominant pattern of inheritance. RESULTS: The
      extracellular matrix showed flocculent material and collagen fibrils with
      structural abnormalities and variation in diameter. Increased numbers of oxytalan
      fibers were identified; however, elastic fibers were rare in the analyzed areas.
      CONCLUSIONS: The structural alterations found in HGF appear similar to those
      described in certain other heritable collagen disorders, suggesting that HGF
      should be included in the group of hereditary diseases in which connective tissue
      alterations have a distinct pattern, in contrast to reactive fibrotic gingival
      enlargements with no genetic component.

PMID- 11458250
TI  - Effect of interleukin-6 deficiency on the formation of periapical lesions after
      pulp exposure in mice.
AB  - OBJECTIVE: The multifunctional cytokine interleukin-6 (IL-6) has actions on
      multiple cell types, including promotion of the development of immune cells and
      osteoclasts. Periapical inflammation as the result of root canal infection is
      characterized by the accumulation of inflammatory cells and bone resorption. The
      effect of IL-6 on periapical lesion formation after pulpal infection is unknown.
      We sought to determine whether deletion of IL-6 affects periapical lesion
      formation after pulp exposure. METHODS: Molar pulps of homozygous IL-6 knock-out
      mice (IL-6(-/-), strain B6, 129-Il6tm1Koe ) and wild-type mice (IL-6(+/+)) were
      exposed, and the mice were killed at 1, 2, 3, 5, and 8 weeks after the exposure.
      Mouse jaws were decalcified and prepared for histologic examination of periapical
      lesions. RESULTS: The IL-6(-/-) mice developed larger periapical lesions more
      rapidly than did the IL-6(+/+) mice. CONCLUSIONS: IL-6 deletion promoted
      periapical lesion development.

PMID- 11458251
TI  - Clinical performance of 3 endodontic sealers.
AB  - OBJECTIVE: Calcium hydroxide is used in endodontics as an interappointment
      dressing. Its inclusion in salicylate resin or zinc oxide-eugenol-based sealers
      for filling root canals also may lead to a better treatment outcome. The purpose
      of the present study was to compare the clinical/radiographic treatment outcome
      of 3 sealers, 2 of which contain calcium hydroxide. STUDY DESIGN: Two hundred and
      four teeth underwent a standardized endodontic treatment regimen and were
      assigned to 1 of 3 groups at the time of root filling: group PS, teeth filled
      with gutta-percha and Procosol sealer; group CR, teeth filled with gutta-percha
      and CRCS sealer; and group SA, teeth filled with gutta-percha and Sealapex
      sealer. The results of the treatment were assessed yearly for up to 4 years by
      clinical and radiologic (periapical index scores) controls. The ridit statistic
      (r) was used to compare PAI scores among the groups. RESULTS: The overall
      treatment results were comparable with, but slightly poorer than, results
      previously obtained from patients seen at the Dental School at the University of
      Oslo. During the first year after filling, the mean ridit value decreased from
      .51 +/- .039 to .31 +/- .042 (Deltar = .20) in the SA group. Corresponding values
      went from .43 +/- .030 to .38 +/- .035 (Deltar = .05) in the PS group and from 37
      +/- .045 to .34 +/- .050 (Deltar = .03) in the CR group. At the 2-year
      examination, teeth in group SA had slightly better periapical conditions (r =.22
      +/-.045) than did teeth in group PA (r = .30 +/- .037) or in group CR (r = .30 +/
      052). The difference was statistically significant at P = .01. By years 3 and 4,
      no significant difference among the groups was detected. CONCLUSIONS: The overall
      influence of the sealer on treatment outcome was small. Root fillings with
      salicylate resin containing Ca(OH)2 may support more rapid healing of apical
      periodontitis or operative trauma, but the results after 3 and 4 years were as
      good for zinc oxide-eugenol-based sealers with or without Ca(OH)2.

PMID- 11458252
TI  - A comparative evaluation of the diagnostic efficacy of film and digital sensors
      for detection of simulated periapical lesions.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic efficacy of
      Ektaspeed Plus film (EPF), a charge-coupled device (CCD), and photostimulable
      phosphor (PSP)-based digital images for detection of simulated periapical
      lesions. STUDY DESIGN: Lesions were simulated in the periapical areas of 24 human
      mandibular sections invested in acrylic using burs of sizes #1, 2, 4, and 6 and
      imaged using EPF, CCD, and PSP sensors. Percent correct response scores,
      sensitivity, and specificity values were computed for all variables. Repeated
      measures analysis of variance and post hoc testing were performed to determine
      the effects of imaging modality, observer, and lesion sizes with respect to
      lesion detection. RESULTS: EPF displayed the highest sensitivity and specificity,
      followed by PSP and CCD images (P <.001). Percent correct score was the highest
      for 3 of 4 observers when EPF was used. Analysis of variance revealed
      significance (P <.001) with respect to all variables. Observers with experience
      in digital image-viewing performed better than those without such experience (P
      <.001). Intraobserver agreement was fair (kappa = 0.5). CONCLUSIONS: EPF
      outperformed CCD and PSP images when observers could manipulate image
      characteristics.

PMID- 11458253
TI  - Morphology of the mandibular fossa and inclination of the articular eminence in
      patients with internal derangement and in symptom-free volunteers.
AB  - OBJECTIVE: The purpose of this study was to evaluate temporomandibular joint
      morphology and to compare possible structural variations in the temporomandibular
      joint anatomy of symptomatic anterior disk displacement patients with possible
      structural variations in the temporomandibular joint anatomy of symptom-free
      volunteers. STUDY DESIGN: Fifty-six symptomatic patients and 25 symptom-free
      volunteers were included in this study. All subjects had bilateral high
      resolution magnetic resonance imaging scans performed in the sagittal (closed and
      open) positions. Disk positions were evaluated with these images, and the
      patients were accordingly classified into 4 diagnostic groups. The angulation
      between the Frankfort horizontal plane and the posterior slope of the articular
      eminence, as well as the width and depth of the glenoid fossa and the articular
      tuberculum, were automatically measured with the aid of a computer. RESULTS: The
      Mann-Whitney U test demonstrated significant differences in the angular and
      linear values obtained in disk displacement with reduction patients in comparison
      with the values obtained in patients with disk displacement without reduction and
      in symptom-free volunteers. CONCLUSION: It is proposed that a steeper posterior
      slope and higher tuberculum articulaire are predisposing factors for the
      development of disk displacement with reduction. Flattening of the eminence may
      progress in time, leading to the onset of disk displacement without reduction.

PMID- 11458254
TI  - Comparison between PAI and quantitative digital radiographic assessment of apical
      healing after endodontic treatment.
AB  - OBJECTIVE: The purpose of this study was to compare both subjective (Periapical
      Index, PAI) and objective (densitometric) radiographic evaluation of healing
      after endodontic treatment for apical periodontitis. STUDY DESIGN: Standardized
      radiographs of 103 teeth taken at baseline (immediately after endodontic
      treatment) and at 1, 4, 12, 26, and 52 weeks were evaluated. Consensus PAI scores
      obtained from 7 calibrated observers served as "true scores." Densitometric
      estimates of periapical status were obtained from digitized radiographs as the
      ratio of mean gray value of an area of radiolucency (AR) to an adjacent and
      similar-sized normal (N) area (AR/N). The selected regions of interest on
      baseline images were automatically superimposed on postoperative images. All
      estimates of change were measured with respect to baseline. The subtraction
      estimate was expressed as AR(S)-N(S). Linear regression was used to analyze
      longitudinal changes against baseline and to assess the relationship of PAI and
      AR/N and of change in PAI with respect to baseline and AR(S)-N(S). RESULTS: Five
      hundred fifty-six PAI scores were generated, with 547 AR/N values and 444
      subtraction estimates. PAI, AR/N, and AR(S)-N(S) demonstrated statistical
      significance for change (P < or = .05) starting at 12 weeks. PAI was
      significantly correlated with AR/N (P < .0001), as was CHPAI with AR(S)-N(S) (P <
      .024). CONCLUSION: The PAI and 2 densitometric estimates (AR/N and AR(S)-N(S))
      detected healing of apical periodontitis at 12 weeks after treatment. No
      difference could be observed among the methods.

PMID- 11458255
TI  - Radiographic evaluation of malignant fibrous histiocytoma affecting maxillary
      alveolar bone: a report of 2 cases.
AB  - OBJECTIVE: The purpose of this study was to evaluate the radiographic findings of
      malignant fibrous histiocytoma (MFH) and to discuss the contribution of these
      findings to a differentiation of MFH from other malignant tumors of the head and
      neck. STUDY DESIGN: Two cases of MFH of the maxillary sinus affecting the
      alveolar bone were evaluated radiographically and scintigraphically. RESULTS: We
      reported the following findings, which have only seldom been described: the
      presence of fairly well-demarcated bone destruction in the intraoral radiograph;
      the relatively smooth surface, uniform density, or no necrotic area of the tumor;
      in computed tomograph images showing the clear separation of the tumor from
      surrounding soft tissues; bone scintigraphs reflecting the periosteal reaction to
      tumor invasion; and lymphoscintigraphy of the metastatic lymph nodes. CONCLUSION:
      We evaluated the radiographic findings from 2 cases of MFH and describe findings
      that may aid in the differentiation of MFH. These radiographic features may help
      dentists differentiate MFH from other malignant tumors in the head and neck,
      although MFH is a rare disease and there are no radiographic findings that would
      indicate a specific diagnosis of MFH.

PMID- 11458257
TI  - Terminal hinge movement of the mandible. 1957.

PMID- 11458258
TI  - Immediate stabilization at stage II of zygomatic implants: rationale and
      technique.
AB  - The severely resorbed maxilla presents a challenge for the maxillofacial surgeon
      and the restorative dentist planning implant restorations. The Zygomatic implant,
      as introduced by Branemark, allows for the surgical placement of implants to
      restore resorbed maxillae without major grafting procedures. A minimum of 2
      implants in the anterior maxilla are used in conjunction with 1 implant in each
      zygoma to support a prosthesis. Fabricating a passive bar to connect the implants
      at phase II surgery may require 1 to 2 days. With the adhesive abutment cylinder
      luting technique, a rigid framework can be delivered within 1 hour of uncovering
      the implants. This approach saves considerable time over conventional techniques
      and allows for the restoration of severely resorbed maxillae in an efficient and
      routine manner. The technique also eliminates the necessity for a technician to
      be available on-site for the procedure.

PMID- 11458259
TI  - Operator-induced compressive axial forces during implant gold screw fastening.
AB  - STATEMENT OF PROBLEM: The gold screw of an implant is put under tension during
      fastening. An increase in operator-induced compressive axial force during
      fastening may diminish screw tension, lower the friction between the screw
      threads, and allow for increased tightening torque. PURPOSE: This study was
      undertaken to assess and compare the compressive axial forces and torques placed
      simultaneously on implant gold screws by persons with varying degrees of
      expertise. MATERIAL AND METHODS: A calibrated electric torque driver was used to
      fasten implant gold screws. Three groups of operators with various levels of
      implant experience (faculty [F; n = 4], prosthodontic residents [R; n = 4], and
      undergraduate dental students [S; n = 6]) were asked to repeatedly tighten and
      loosen a new gold abutment screw into a standard 3.75-mm diameter Branemark
      abutment. Compressive axial forces during torquing were assessed over the
      tightening time by means of a miniature load cell adapted to the electric torque
      driver. Each operator repeated the experiment 3 times after calibration. Within
      operator and between operator reliability were evaluated. RESULTS: Loosening
      compressive axial forces were always higher than tightening compressive axial
      forces, and peak torque was less on loosening than tightening. Faculty placed a
      smaller range of forces on the screws (mean = 3.29 N, SD +/- 1.45 N) than did the
      residents (mean = 2.74 N, SD +/- 1.96) or the students (mean = 3.01 N, SD +/-
      2.54). CONCLUSION: The clinical experience of operators seems to influence their
      application of compressive axial force during gold screw tightening. Less torque
      during unfastening of gold screws seems to be related to increased axial loading.

PMID- 11458260
TI  - Stress levels for well-fitting implant superstructures as a function of
      tightening force levels, tightening sequence, and different operators.
AB  - STATEMENT OF PROBLEM: Unfavorable stress distribution and occlusal overload have
      been reported to result in failures ranging from screw loosening to loss of
      osseointegration. PURPOSE: The purpose of this study was to assess the effect of
      different tightening forces and sequences, with different operators, on stresses
      generated on an accurately fitting implant superstructure on multiple working
      casts made with a splinted impression technique. MATERIAL AND METHODS: The
      effects of different tightening forces (10 and 20 Ncm) were assessed with the use
      of 30 stone casts made from a metal master model with a splinted impression
      technique. Stresses generated were recorded by 4 strain gauges attached to the
      superior surface of the master framework. A multiple analysis of variance with
      repeated measures was performed to test for significant differences among the
      groups. RESULTS: Tightening force values at 10 Ncm ranged from 150.43 to 256 Ncm.
      At 20 Ncm, microstrain values ranged from 149.43 to 284.37 Ncm. Microstrain
      values related to the sequence of tightening ranged from 150.8 to 308.43 Ncm
      (left to right) and 154.63 to 274.80 Ncm (right to left). For the different
      operators, microstrain values ranged from 100.13 to 206.07 Ncm. No statistically
      significant differences among the variables of tightening force, tightening
      sequence, and operators were found ( P >.05). The interaction between groups and
      strain gauges was also found to be nonsignificant (P >.05). CONCLUSION: The
      potential of variable tightening force and tightening sequence to generate
      unfavorable preload stresses can be minimized through use of the splinted
      impression technique, which ensures an accurately fitting superstructure.

PMID- 11458261
TI  - Implant abutment screw rotations and preloads for four different screw materials
      and surfaces.
AB  - STATEMENT OF PROBLEM: Chronic implant screw loosening remains a problem in
      restorative practices. Some implant manufacturers have introduced abutment screws
      with treated surfaces in an effort to increase preload and reduce potential
      loosening. Purpose. This study evaluated the materials and surfaces of 4
      commercially available abutment screws on preload generation. MATERIAL AND
      METHODS: Twenty of each of the following abutment screws-Gold-Tite (Gt), TorqTite
      (Tt), gold alloy (Ga), and titanium alloy (Ta)-were divided into 2 groups.
      Measurements were recorded for each abutment screw on a mounted 3.75 x 18 mm
      external hex implant with a titanium abutment. Rotational angle measurements were
      conducted on the 4 abutment screws at 20 and 32 Ncm. Removal torque values were
      recorded and used to indirectly generate preload values. Random implant block
      specimens were sectioned and qualitatively evaluated with an SEM. RESULTS: At 20
      and 32 Ncm, the largest rotational angles were recorded for the Tt groups: 21.2
      +/- 3.1 degrees and 38.1 +/- 8.7 degrees, respectively. The greatest preload
      values at 20 and 32 Ncm were calculated for the Gt groups: 596.8 +/- 101.2 N and
      1015.3 +/- 191.2 N, respectively. SEM analysis of the 4 implant block specimens
      revealed mating thread contacts located in the middle portion of the superior
      surface of the abutment screw thread. The greatest number of mating thread
      contacts were seen in the Gt implant block specimen (14 of 20 possible thread
      contacts). CONCLUSION: The Gt and Tt abutment screws with enhanced surfaces that
      help reduce the coefficient of friction produced greater rotational angles and
      preload values than the conventional gold alloy and titanium alloy screws.

PMID- 11458262
TI  - Annual review of selected dental literature: report of the committee on
      scientific investigation of the American Academy of Restorative Dentistry.

PMID- 11458263
TI  - An evidence-based assessment of occlusal adjustment as a treatment for
      temporomandibular disorders.
AB  - STATEMENT OF PROBLEM: Occlusal adjustment therapy has been advocated as a
      treatment modality for temporomandibular disorders. In contrast to this position,
      a panel at the 1996 National Institute of Health technology assessment conference
      on TMD indicated that no clinical trials demonstrate that occlusal adjustment is
      superior to noninvasive therapies. PURPOSE: This article summarizes the published
      experimental studies on occlusal adjustments and temporomandibular disorders.
      MATERIAL AND METHODS: Eleven research experiments involving 413 subjects with
      either bruxism (n = 59), temporomandibular disorders (n = 219), headaches and
      temporomandibular disorders (n = 91), or chronic cervical pain (n = 40) were
      selected for critical review from the English dental literature. RESULTS: Three
      experiments evaluated the relationship between occlusal adjustment and bruxism.
      Six experiments evaluated occlusal adjustment therapy as a treatment for patients
      with primary temporomandibular disorders. One experiment looked at occlusal
      adjustment effect on headache/temporomandibular disorder symptoms; another looked
      at its effect on chronic neck pain. Most of these experiments used a mock
      adjustment or a comparison treatment as the control condition in adults who had
      an existing nonacute general temporomandibular disorder. Overall, the data from
      these experiments did not demonstrate elevated therapeutic efficacy for occlusal
      adjustment over the control or the contrasting therapy. CONCLUSION: The
      experimental evidence reviewed was neither convincing nor powerful enough to
      support the performance of occlusal therapy as a general method for treating a
      nonacute temporomandibular disorder, bruxism, or headache.

PMID- 11458264
TI  - Occlusal plane discrepancies generated by transverse horizontal axis deviations.
AB  - STATEMENT OF PROBLEM: Any deviation from the patient's rotational axis of the
      mandible during closure and the arc of closure on an articulator has been
      reported to produce occlusal discrepancies. These discrepancies can affect
      diagnostic planning procedures and the occlusal relationships of restorations.
      PURPOSE: This study investigated the magnitude and types of occlusal errors
      produced by deviations between the patient's transverse horizontal axis and the
      axle on the articulator. MATERIAL AND METHODS: A simplified monoplane model was
      diagrammatically analyzed for deviations from the model's true transverse
      horizontal axis. Axis deviations of 5 mm were used in 8 different directions from
      the true transverse horizontal axis of the model. Changes in the orientation of
      the mandibular plane to the maxillary plane were illustrated diagrammatically.
      These changes were quantified by geometric and trigonometric assessments.
      RESULTS: All axis deviations produced mandibular plane orientation errors with
      angular plane malalignment to the maxillary plane on complete closure. These axis
      deviations also produced anterior-posterior shifting of the mandibular plane
      relative to the maxillary plane. CONCLUSION: Several different types of planar
      shifting and angular discrepancies were demonstrated from deviations away from
      the true transverse horizontal axis.

PMID- 11458265
TI  - The effect of thermal change on various dowel-and-core restorative materials.
AB  - STATEMENT OF PROBLEM: Severe thermal stresses caused by food-induced temperature
      changes may result in dowel-and-core failure. PURPOSE: This study investigated
      the influence of thermal stresses on various combinations of dowel-and-core
      materials of a restored endodontically treated incisor. MATERIAL AND METHODS: A 2
      dimensional finite element model was constructed in a labiolingual cross
      sectional view of a maxillary central incisor, a dowel, a core, and the
      supporting tissues to investigate thermal stress distribution. Four combinations
      of dowel-and-core materials were used: (1) gold/gold, (2) stainless steel/resin
      composite, (3) stainless steel/amalgam, and (4) carbon fiber-reinforced
      composite/resin composite. For thermal analysis, a cold irritant (0 degrees C)
      was applied on the outer surface of a metal-ceramic crown for 7 seconds. RESULTS:
      The metal dowel and core generated lower thermal stresses in the restorations and
      dentin than the nonmetallic dowel and cores. CONCLUSION: Stress level is closely
      related to the degree of thermal gradient. The nonmetallic dowel and cores
      generated greater thermal stresses than metal dowel and cores.

PMID- 11458266
TI  - Marginal adaptation of inlay-retained adhesive fixed partial dentures after
      mechanical and thermal stress: an in vitro study.
AB  - STATEMENT OF PROBLEM: There are no studies that analyze the long-term durability
      of minimally invasive fixed partial dentures (FPDs) by comparing different
      methods of adhesive bonding. PURPOSE: This in vitro study examined the influence
      of cavity design and operative technique on the marginal adaptation of resin
      bonded composite FPDs. MATERIAL AND METHODS: Slot-inlay tooth preparations with
      cavity margins located in enamel were prepared in 18 maxillary canines and 18
      maxillary first molars designated as abutments. The specimens were divided
      equally into 3 experimental groups. In all groups, butt joint tooth preparations
      were created in canines and molars. In group 2, canines were prepared
      additionally with a 1.5-mm wide palatal bevel in enamel. After pretests with
      modification spaces of 11 and 17 mm (length), 2 missing premolars were replaced
      by the ceromer Targis and reinforced with the glass-fiber material Vectris. The
      prostheses were inserted with Tetric Ceram with use of an ultrasonic-supported,
      high-viscosity technique. Restorations were selectively bonded to cavity finish
      lines in groups 1 and 2 ("selective bonding"). In group 3, restorations were
      bonded totally to the whole cavity surface ("total bonding"). The restorations
      were stressed in a computer-controlled masticator. Marginal quality was examined
      with an SEM at x 200. RESULTS: The percent area of optimal margins after
      thermomechanical loading between composite and enamel in each group was as
      follows: group 1, 86.2% +/- 12.3% for canines and 95.5% +/- 3.5% for molars;
      group 2, 95.3% +/- 2.1% for canines and 96.2% +/- 2.7% for molars; and group 3,
      95% +/- 0.9% for canines and 86.4% +/- 3.2% for molars. The marginal quality for
      molars inserted with total bonding was significantly lower (P< or =.05).
      CONCLUSION: Within the limitations of this study, the selective bonding technique
      for slot inlay-retained fixed partial dentures resulted in a negligible loss of
      marginal quality after extensive mechanical and thermal stress. The selective
      bonding technique is recommended for box-shaped cavity preparations.

PMID- 11458267
TI  - Comparison of castability and surface roughness of commercially pure titanium and
      cobalt-chromium denture frameworks.
AB  - STATEMENT OF PROBLEM: Titanium is a biocompatible material, but it is not widely
      used in clinical dentistry for conventional removable denture frameworks. Little
      research exists on its applicability. PURPOSE: This study compared the casting
      accuracy and roughness of titanium and cobalt-chromium denture frameworks.
      MATERIAL AND METHODS: Twenty Kennedy Class II, Division 1 removable partial
      denture frameworks were fabricated with commercially pure titanium (n = 10) and a
      cobalt-chromium alloy (n = 10). The casting accuracy of each framework was
      determined by visual, radiographic, and microscopic methods. The roughness of
      each polished framework surface was analyzed with atomic force microscopy.
      RESULTS: The clinical fit, porosities, and microporosities of both types of metal
      frameworks were qualitatively similar. The surface roughness of polished pure
      titanium and cobalt-chromium frameworks was 104.43 +/- 69.24 nm and 133.91 +/-
      40.92 nm, respectively. This difference was not statistically significant (P
      >.05). CONCLUSION: The clinical fit, porosity, and surface roughness of the
      titanium and cobalt-chromium frameworks fabricated for this study were
      comparable.

PMID- 11458268
TI  - A method of making casts for permanent, complete acrylic resin denture bases
      without blocking out undercuts.

PMID- 11458269
TI  - Use of a wire wheel lathe attachment in the dental laboratory.

PMID- 11458270
TI  - Angiogenesis-dependent diseases and angiogenesis therapy.
AB  - The discovery of the molecular mechanisms of physiological vasculogenesis and
      pathological angiogenesis helped to recognize two classes of diseases: one where
      the therapeutic angiogenesis can repair the tissue damages (arteriosclerosis,
      myocardial infarction, limb ischemia) and the other one where inhibition of
      pathological angiogenesis can cure the disease or delay its progression
      (retinopathies, benign and malignant angiogenic tumors, progression of malignant
      tumors). Although there are an exponentially growing number of new synthetic
      molecules characterized mainly by antiangiogenic properties, the discovery of a
      large battery of natural pro- and anti-angiogenic factors suggests that this may
      provide a more physiological approach to treat both class of angiogenesis
      dependent diseases in the near future.

PMID- 11458272
TI  - The hepatic glycogenoreticular system.
AB  - One of the major liver functions is the ability of hepatocytes to store glucose
      in the form of glycogen for various purposes. Beside glucose production and
      secretion, the synthesis of glucuronides and ascorbate has been reported to be
      dependent on the extent of the glycogen stores and on the rate of glycogenolysis
      in the liver. It is common that the final steps of these pathways are catalysed
      by intraluminally orientated enzymes of the endoplasmic reticulum, which are
      supported by transporters for the permeation of substrates and products. On the
      basis of the close morphological and functional proximity of glycogen, glycogen
      dependent pathways and the (smooth) endoplasmic reticulum we propose to use the
      term  glycogenoreticular system  for the description of this export-orientated
      hepatocyte-specific metabolic unit.

PMID- 11458271
TI  - Shared pathways: death receptors and cytotoxic drugs in cancer therapy.
AB  - Death ligands (TNF, FasL, TRAIL) and their respective death receptor signaling
      pathways can be used to induce tumor cells to undergo apoptosis. Chemotherapeutic
      drugs can induce apoptosis and the upregulation of death ligands or their
      receptors. Downstream events following cytotoxic stress-induced DNA damage and
      the signaling pathways that lead to the induction of apoptosis may be either
      dependent or independent of death receptor signaling. The involvement of the Fas
      signaling pathway in chemotherapy-induced apoptosis has been the most extensively
      studied, with the current emergence of information on the TRAIL signaling
      pathway. Fas-mediated and chemotherapy-induced apoptosis can converge at the
      level of the receptor, FasL, DISC formation, activation of the initiator caspase
      8, at the level of the mitochondria, or at the level of downstream effector
      caspase activation. Convergence is influenced by the specific form of DNA damage,
      the cellular environment, and the specific pathway(s) by which death receptor
      mediated or drug-mediated apoptosis are induced. This review discusses the
      different levels of interaction between signaling pathways in the different forms
      of cell death.

PMID- 11458273
TI  - Association of a alpha1 acidic glycoprotein and squamous cell carcinoma of the
      head and neck.
AB  - Serum from patients with different malignancies contain an abnormal concentration
      of a a1-acidic-glycoprotein (AAG) and also, increased levels of AAG are
      associated with the presence of tumor mass. In the present report, serum levels
      of AAG were measured by radial immunodiffusion in squamous cell carcinoma of the
      head and neck (SCCHN) patients taking into account disease status parameters such
      as tumor localization, stage and extension of disease. Immunohistochemical
      methods, SDS-PAGE and Western-blotting were employed to study the expression of
      AAG and a carbohydrate related antigen (sialyl Lewis x) in tumor tissues and
      derived fractions. AAG showed abnormal levels in 7/15 oral cavity tumor patients 
      sera, 2/5 oropharynx and 5/10 larynx tumors; increased AAG serum levels belonged
      to patients with disseminated disease. On the other hand, the presence of AAG and
      sialyl Lewis x were demonstrated in carcinoma cells and in derived fractions from
      tumor tissues belonging to patients with elevated AAG serum levels. In the
      present study, we have found elevated levels of AAG in serum samples from SCCHN
      patients; these neoplastic cells are capable to express AAG.

PMID- 11458274
TI  - Prognostic histological and immune markers of renal cell carcinoma.
AB  - Recent development on the fields of molecular genetics and immunology of human
      renal cell carcinoma (RCC) have resulted in more successful treatment of advanced
      and metastatic RCCs. Re-evaluation of the prognostic/predictive data aim the
      initial tumor staging of RCC patients to achieve better patient selection for
      immune and gene therapy. 125 RCC patients diagnosed according to the Heidelberg
      histological classification, graded, Robson staged, immune treated (Interferon-a
      a+ Vinblastine or Broncho-Waxom/Decaris) were followed-up clinically for 36
      months. Tumor immunity markers by immunohistochemistry of tumor infiltrating
      lymphocytes (TIL) were detected by immunoperoxidase methods using monoclonal
      antibodies. Tumoral immune complexes (TIC) were visualized by fluorescent
      polyclonal antibodies. Histologically oncocytomas defined a better (p<0.02) and
      sarcomatous RCCs a worse (p<0.01) follow-up prognosis. Basically, the metastatic
      status (related with the stage and grade) determined the clinical outcome
      (p<0.00002) of the RCC patients. Tumoral immune complexes (TIC) were weak
      positive, while tumor infiltrating lymphocytes (TIL) weak negative predictors of
      the succes of Broncho-Waxom/Decaris immune therapy. Molecular genetic based
      histological classification, grade, stage and metastatic status parameters
      together with some tumor immunity parameters (TIL, TIC) can predict the success
      of immunotherapy of RCC patients.

PMID- 11458275
TI  - DNA ploidy analyses in 218 consecutive Pakistani breast cancer patients: does it
      add anything?
AB  - An analysis was made to evaluate the significance of DNA ploidy in the biology
      and prognosis of breast carcinoma. This was done by estimating the correlation of
      DNA ploidy with other established prognostic markers of breast cancer, namely
      tumor size, tumor grade, lymph node metastasis and S-phase fraction. From 1995 up
      to year 2000 ploidy analysis was performed on 218 consecutive cases of
      infiltrating breast carcinoma by flow cytometry using formalin fixed paraffin
      embedded material. From the laboratory record, data regarding other pathological
      variables was retrieved. No correlation could be found between DNA ploidy and
      tumor grade, nor could there be found a correlation with tumor size. For lymph
      node metastasis there was a significant difference between the proportion of
      aneuploids and diploids having metastasis in more than 4 lymph nodes. However, no
      significant difference was found in axillary lymph node positive and negative
      groups when number of positive lymph nodes was not taken into account. The mean
      value of S-phase fraction for the aneuploids and the diploids was also
      insignificantly different. In conclusion DNA ploidy alone did not add much to
      predict tumor behaviour in terms of known pathologic variables.

PMID- 11458276
TI  - Expression of CD34 in gastric cancer and its correlation with histology, stage,
      proliferation activity, p53 expression and apoptotic index.
AB  - The formation of new blood vessels is essential for tumor growth and progression.
      Until today there are only few studies of the immunohistochemical assessment of
      angiogenesis in gastric cancer by the evaluation of the expression of CD34
      antigen. The aim of this study was to analyze the relationship between
      microvessel density (MVD) expressed as the mean count of CD34 immunostained
      vessels and clinicopathologic features of gastric tumors (the histological type
      according to the Lauren classification, tumor grade   G; presence of lymph node
      metastases   N; depth of tumor invasion; stage of disease (UICC-AJCC 1988 1992),
      p53 expression, tumor cell proliferative activity described as the Ki67 labelling
      index and apoptotic index of tumor cells   TUNEL method). We assessed formalin
      fixed, paraffin-embedded tissue samples obtained during potentially radical
      gastrectomy from 58 patients with primary gastric adenocarcinoma. The
      representative tissue blocks from each tumor were used for the
      immunohistochemical assay and examined by two pathologists independently. MVD was
      counted in five tumor areas of the most intensive neovascularization (x 200 field
      by light microscopy) and the mean counts were recorded. The mean MVD (CD34
      expression value+/-SD) in this study was 43,15+/-19,8 per x 200 field. The study
      demonstrated the statistically significant correlation between MVD and two main
      histological parameters: tumor grading (p < 0.001) and tumor histological type
      according to Lauren s classification (p<0.05). In well   and moderately  
      differentiated tumors (G1/2) MVD was significantly lower in comparison to the
      group of poorly differentiated cancer   G3 (mean value: 31,62 vs. 49,89). MVD was
      higher in diffuse type of gastric cancer comparing to intestinal type (50.05+/
      19,03 vs. 39.17+/-20,09). However, the authors failed to find a significant
      correlation between MVD and other investigated histopathological features in
      malignant gastric tumors. The close relationship between CD34 immunostaining,
      gastric cancer tumor vascularity and main histological parameters was shown in
      this study. It can be stated that analysis of expression of angiogenesis in
      gastric cancer may be helpful for better estimation of hematogenous recurrence
      and the selection of the group of patients for adjuvant antiangiogenic treatment.

PMID- 11458277
TI  - Hepatitis C virus infection in patients with essential mixed cryoglobulinemia,
      multiple myeloma and chronic lymphocytic leukemia.
AB  - Increased prevalence of HCV infection in some lymphoproliferative diseases has
      been recently reported. In the present study, the frequency of anti-HCV antibody
      (Ab) together with hepatitis B surface (HBs) antigen (Ag) and anti-HBs Ab were
      determined in 42, 45 and 23 patients with essential mixed cryoglobulinemia (EMC),
      multiple myeloma (MM) and B-cell chronic lymphocytic leukemia (B-CLL),
      respectively. Thirty hospitalized patients with chronic rheumatoid arthritis (RA)
      were also included as a control. Specific antibodies to HCV antigens were
      detected by enzyme linked immunosorbent assay (ELISA) and positive results were
      confirmed by a recombinant immunoblot assay (RIBA). Our results demonstrated anti
      HCV positivity in 69%, 11% and 4.3% of the EMC, MM and B-CLL samples tested,
      respectively. None of the RA patients were found to be anti-HCV positive. No
      significant differences were observed between the patients  groups regarding the
      frequency of HBs Ag and anti-HBs Ab. Considering the low incidence of HCV
      infection in the control group and the normal population, these results confirm
      and extend previous reports on the possible role of HCV infection in the etiology
      of EMC and further suggest involvement of this virus in a subset of MM.

PMID- 11458278
TI  - Heat shock protein 60 in corpora amylacea.
AB  - Heat shock protein 60 representation in the corpora amylacea of the brain was
      investigated in five different neurological diseases. In the cases with cerebral
      infarct, amyotrophic lateral sclerosis, multiple sclerosis, acute disseminated
      encephalomyelitis and primary tumors of the nervous system the corpora amylacea
      showed similar appearance with strong HSP-60 positivity in all investigated
      disorders at the predilection sites. In the inflammatory diseases, besides
      corpora amylacea, several cellular elements exhibited HSP-60 immunostaining too.
      In these cases, the widespread HSP-60 immunoreactivity associated with relative
      moderate corpora amylacea production as compared to other diseases. From this
      contradiction we concluded the corpora amylacea participate in the cellular
      stress reaction but stress protein synthesis certainly is not the primary event
      in corpora amylacea formation. In the development of the corpora amylacea the
      incipient process is most probably degenerative in nature, which later on is
      accompanied by stress protein synthesis and slow growing of these round
      structures designated for a protective role in the brain. However, the role of
      the stress protein synthesis in the corpora amylacea formation and growth was not
      unequivocally answered in this study. It is necessary to perform further
      comparative investigations of the stress protein representation and corpora
      amylacea formation in different diseases which may help in discovering useful
      pathogenetic data and the biological role of this degenerative structure.

PMID- 11458279
TI  - New data on the ultrastructure of the corpus amylaceum (polyglucosan body).
AB  - During the semiquantitative evaluation of the occurrence of the corpus amylaceum
      (CA) in a large quantity of autopsy and biopsy material (1,407 cases),
      electromicroscopical (EM) and scanning EM examinations were carried out on 8
      autopsied cases where CA was demonstrated. The EM examinations appeared to
      underline the astrocytic origin of the CA formation, which is initiated in the
      astrocytic fiber system by glycogen and other carbohydrate polymers. The
      biophysics of the development of the CA is indicative of the same mechanisms as
      for (mainly intracellular) inclusion bodies. The large amount of CA that develops
      at the predilection sites is a consequence of metabolic damage, a large quantity
      of cerebrospinal fluid and recurring disturbances in the barrier functions. The
      abundant CA may cause secondary blood-brain barrier disturbances. This working
      hypothesis demands further investigations and the continuation of research by
      modern immunocytochemical and ultrastructural methods recommended.

PMID- 11458280
TI  - Leiomyosarcoma of the female breast.
AB  - Leiomyosarcomas of the breast are rare tumors. Less than 15 such cases have been
      reported in the literature so far. In this paper authors describe a case of
      leiomyosarcoma of a female breast presenting as a firm lobulated mass, mimicking
      a phylloid tumor radiographically. By fine needle aspiration biopsy, on the
      smears discohesive malignant looking cells were conclusive to a poorly
      differentiated invasive ductal carcinoma of the breast. The mastectomy specimen
      contained a lobulated mass, microscopically showing a partly epithelioid spindle
      cell tumor, immunoreactive for vimentin, desmin, smooth muscle actin antibodies,
      and negative for epithelial markers, hormone and growth factor receptors.
      Axillary lymph nodes were free of tumor. A primary leiomyosarcoma of the breast
      was diagnosed.

PMID- 11458281
TI  - Diet and coronary heart disease: findings from the Nurses' Health Study and
      Health Professionals' Follow-up Study.
AB  - In the last decade, our understanding of the nutrients and foods most likely to
      promote cardiac health has improved substantially, owing in part to the data from
      several large and carefully conducted prospective cohort studies, including the
      Nurses' Health Study (NHS) and Health Professionals' Follow-up Study (HPFS).
      Using more refined dietary assessment tools and multiple measurements, the NHS
      and HPFS have provided a wealth of information not only on major types of fat and
      different classes of fatty acids, but also other aspects of diet, including
      antioxidants, folate, fiber, dietary glycemic load, and overall dietary patterns.
      These studies, along with metabolic, clinical and other epidemiological studies,
      have provided strong evidence for a major role of dietary modification in the
      prevention of coronary heart disease (CHD).

PMID- 11458282
TI  - Nutritional research within the Framingham Heart Study.
AB  - Fifty years of research at the Framingham Heart Study have made important
      contributions to the diagnosis and treatment of cardiovascular disease (CVD).
      Within the scope of this prospective population-based cohort study, research
      investigations from the Framingham Nutrition Studies have developed and advanced
      nutritional epidemiologic methods, many of which are highlighted here. Ongoing
      nutrition research explores relationship between diet, nutritional status, and
      the development of chronic diseases, including CVD. This paper summarizes key
      findings from decades of nutrition research within the Framingham Heart Study.
      Cross-sectional and longitudinal investigations are described, including recent
      research on dietary patterns and coronary heart disease risk among women.
      Implications for the development of national nutrition policy, population-based
      dietary guidance for chronic disease prevention, and nutrition-related health
      promotion campaigns for CVD risk reduction are discussed.

PMID- 11458283
TI  - Diet and cardiovascular diseases.
AB  - In spite of the decreasing trend in age-adjusted cardiovascular disease mortality
      in Western European countries, an increase in the cardiovascular morbidity is
      expected because of the ageing of the population. Consequently the health care
      cost for these diseases will increase. This article focuses on the role of diet
      in the occurrence of cardiovascular diseases. Total and HDL cholesterol are major
      determinants of coronary heart disease. Saturated and trans fatty acids have a
      total and LDL cholesterol elevating effect and unsaturated fatty acids a lowering
      effect. N-3 polyunsaturated fatty acids seem to have a protective effect on
      coronary heart disease occurrence independent of cholesterol. Dietary
      antioxidants could be of importance because they may prevent oxidation of the
      atherogenic cholesterol rich LDL lipoproteins. There is however no convincing
      evidence that either vitamin E, carotenoids or vitamin C protect against coronary
      heart disease. Observational research has shown that flavonols, polyphenols with
      strong antioxidant properties present in plant foods, may protect against
      coronary heart disease. Blood pressure is a major determinant of coronary heart
      disease and stroke. Historically salt is viewed as the most important dietary
      determinant of blood pressure. Recent research shows that also a low-fat diet
      rich in potassium, calcium and magnesium lowers blood pressure substantially.
      This suggests a multifactorial influence of different nutrients on blood
      pressure. It can be concluded that a diet low in saturated and trans fatty acids
      and rich in plant foods in combination with regular fish consumption is
      associated with a low risk of cardiovascular mortality.

PMID- 11458284
TI  - Nutrition and cardiovascular disease in Finland since the early 1970s: a success
      story.
AB  - This paper describes the Finnish experience on the population strategy to prevent
      cardiovascular disease with special reference to diet. Systematic work to lower
      the risk factors of cardiovascular disease started in the early 1970s with the
      North Karelia project and rapidly expanded to cover the whole country. The main
      aims were to change the type of fats used, to lower sodium intake and to increase
      vegetable and fruit consumption. Concurrently, a comprehensive monitoring system
      was developed including regular population surveys every five years. During the
      period 1972-1997 major changes took place in the diet as well as in blood
      pressure and serum cholesterol levels. At the same time, cardiovascular mortality
      decreased dramatically. The Finnish experience shows that dietary changes are
      possible but require a persistent and comprehensive intervention.

PMID- 11458285
TI  - Diet and atherosclerosis.
AB  - Everything in the diet can affect cholesterolemia and experimental
      atherosclerosis. Dietary cholesterol has relatively little effect on blood
      cholesterol. Saturated fat is a major factor in cholesterolemia. In rabbits,
      triglyceride structure affects atherosclerosis but not blood cholesterol. Protein
      and carbohydrate effects are secondary to those of fat. Soluble fiber lowers
      blood lipid levels. In the United States the mortality from heart disease (age
      adjusted cases per 100,000) has been falling since 1968. The "French Paradox" is
      attributed variably to red wine, exercise or other factors but no generally
      accepted explanation is available. One area of nutrition research that is almost
      untouched is that of interaction of nutrients which may explain some of the
      dichotomies. A new trend to study dietary patterns rather than specific dietary
      components may help to elucidate observed effects. For healthy people the most
      reasonable dietary advice is moderation, balance and variety.

PMID- 11458286
TI  - Influence of dietary fat type on arterial thrombosis tendency.
AB  - Cardiovascular disease has a multifactorial aetiology, as is illustrated by the
      existence of numerous risk indicators, many of which can be influenced by the
      dietary fat type. It should be recalled, however, that only after a cause-and
      effect relationship has been established between the disease and a given risk
      indicator (called a risk factor in that case), modifying this factor can be
      expected to affect disease morbidity and mortality. In this review, effects of
      dietary lipids on cardiovascular risk are considered, with special emphasis on
      modification of arterial thrombosis and platelet thrombotic processes,
      coagulation and fibrinolysis. Although epidemiological studies do not give
      entirely consistent results, replacement of dietary saturated by unsaturated
      fatty acids generally lowers cardiovascular morbidity and mortality. The few
      (secondary) prevention studies reported so far confirmed this for fish oil or
      fish oil concentrates, as well as for vegetable oils rich in oleic-, linoleic- or
      a-linolenic acids. Animal thrombosis models demonstrated that dietary unsaturated
      fatty acids reduce arterial thrombosis tendency as compared to saturated fatty
      acids. Using restenosis after percutaneous transluminal coronary angioplasty
      (PTCA) and occlusion of coronary artery bypass grafts (CABG) as human models of
      arterial thrombosis, fish oil treatment has been shown to have an anti-thrombotic
      effect, but results are inconsistent (PTCA) or need confirmation (CABG). Major
      thrombotic and anti-thrombotic conditions and processes include endothelial
      integrity, thrombotic functions of blood platelet, coagulation, and fibrinolysis.
      The dietary fat type can affect endothelial integrity, but results are
      inconsistent and often difficult to interpret in terms of arterial thrombosis
      tendency. The same can be concluded for platelet aggregation, especially because
      results of dietary interventions often depend on the aggregation measuring
      technique. Novel well-validated methods are required to solve this problem.
      Dietary fats can affect certain factors involved in blood coagulation and
      fibrinolysis. Thus, Factor VII activity is increased by the fat content of the
      diet. However, the dietary fat type seems of less importance. Studies addressing
      the effect of specific fatty acids on extrinsic clotting and thrombin formation
      in vivo did not produce consistent results. The same holds for the dietary fatty
      acid effects on promoters and inhibitors of the plasma fibrinolytic potential.
      Although trans unsaturated fatty acids may increase cardiovascular risk, this is
      probably not mediated by effects on arterial thrombosis.

PMID- 11458287
TI  - Diet and stroke.
AB  - In industrialized countries, stroke is the most frequent life-threatening
      neurological disorder. The mortality trend for stroke appears to be similar to
      that of coronary heart disease (CHD) in different countries. Thus the dietary
      changes that protect from CHD, may also protect from stroke. The purpose of the
      present paper is not to review exhaustively the associations between foodstuffs
      and stroke. It is rather to emphasize a few important relationships that may be
      conducive to efficient recommendations in Public Health. The intake of saturated
      fat, considered as the main environmental factor for CHD, does not appear to be
      also closely related to stroke. It has even been observed in the Framingham
      prospective study, that saturated fats were associated with a protective effect
      on stroke. The multivariate analysis of the ecological study reported in the
      present paper suggests that the villain for stroke could be the high intake of
      linoleic acid, the main polyunsaturated fatty acid prescribed through the world,
      to most of the CHD patients. Observation and intervention studies suggest that
      the fatty acid with the most efficient protective effect on stroke is alpha
      linolenic acid (ALA) as for CHD clinical manifestations. Also similarly to CHD,
      fruit, vegetables and folic acid, may have important protective effect on stroke.
      Finally, at very moderate intake, alcohol may be related to a similar lowering on
      the risk of stroke as on that of CHD. Nevertheless alcohol, at high intake for
      intoxication (binge drinking) has been associated with up to a 10 fold increased
      in the risk of stroke. Finally, the diet recommendations suggested by the present
      analysis are similar to those used in the Lyon Diet Heart Study and in Finland,
      in the last 20 years. In both of these intervention studies mortality from CHD,
      cancer and stroke have been markedly reduced by more than 50 %.

PMID- 11458288
TI  - Diet and sudden cardiac death.
AB  - The purpose of this paper is to review the evidence that dietary factors, namely
      the ingestion of the n-3 (or w-3) polyunsaturated fatty acids of fish oils can
      prevent fatal cardiac arrhythmias (so-called sudden cardiac death) in
      experimental animals, and probably in humans as well. The mechanism for this
      striking effect results from the ability of these fatty acids to directly
      stabilize electrically every contractile myocyte in the heart. This is
      accomplished by modulation by the free n-3 fatty acids of the ionic currents in
      heart cells; particularly the voltage-dependent sodium currents which initiate
      action potentials and the L-type calcium currents, which initiate release of
      sarcoplasmic reticulum stores of calcium into the cytosol of heart cells. The
      resultant rise in cytosolic calcium concentration initiates contraction of the
      heart cells and the beating rate of the heart. The gradually accumulating
      clinical evidence that these fish oil fatty acids are potent preventors of
      cardiac sudden death in humans will be reviewed. With some 250,000 deaths
      occurring within one hour of the onset of acute myocardial infarctions annually
      in the USA alone and millions more in the whole world, the potential large public
      health benefit from this understanding is evident.

PMID- 11458289
TI  - Alpha-linolenic acid and cardiovascular diseases.
AB  - The intake of saturated fat was postulated to be the main environmental factor
      for coronary heart disease. It was also postulated that the noxious effects of
      saturated fatty acids (FA) was primarily through the increase in serum
      cholesterol. Nevertheless intervention trials either in coronary patients or even
      in primary prevention did not observe significant reduction in cardiac mortality,
      especially sudden death, when the diet was markedly enriched in linoleic acid
      (LA), the most efficient FA to lower serum cholesterol. In intervention trials,
      It is only when the diet was enriched in n-3 FA, especially alphalinolenic acid
      (ALA) that cardiac death was reduced. Studies in animals as well as in vitro on
      myocytes in culture, have shown that ALA was preventing ventricular fibrillation,
      the chief mechanism of cardiac death. Furthermore, studies in rats have observed
      that among n-3 FA, ALA, the precursor of the n-3 family, may be more efficient to
      prevent ventricular fibrillation than eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA). In addition it was demonstrated that ALA was the main
      FA lowering platelet aggregation, an important step in thrombosis, i. e. non
      fatal myocardial infarction and stroke. Thus, without side effects, a higher
      intake of ALA (2g / day) with a ratio of 5/1 for LA/ALA, could possibly
      constitute a nutritional answer to the main cause of morbidity and mortality in
      industrialized countries.

PMID- 11458290
TI  - Trans fatty acids and cardiovascular risk.
AB  - Trans fatty acids are found in partially hydrogenated vegetable oil, in meats,
      and in dairy products. Their effect on blood cholesterol concentrations was
      examined decades ago, but recently there has been renewed interest in
      understanding how trans fatty acids affect blood lipids and lipoprotein
      cholesterol concentrations. Current advice to reduce cardiovascular disease (CVD)
      risk includes decreasing the consumption of saturated and total fat to help
      manage blood cholesterol concentrations. Saturated fat contributes significantly
      to total fat intake and markedly raises blood cholesterol concentrations. Trans
      fatty acids, which are consumed in much smaller quantities, have been shown to be
      modestly hypercholesterolemic in studies that have substituted hydrogenated
      vegetable oils for unhydrogenated oils. In contrast, when partially hydrogenated
      vegetable oils containing trans fatty acids are substituted for cholesterol
      raising saturated fats, blood cholesterol levels are reduced. Partially
      hydrogenated vegetable oils are used in place of saturated fat in many food
      products. These foods can help consumers lower their saturated fat intake to
      achieve dietary recommendations. The following review critically examines the
      role of hydrogenated fats in the food supply, the metabolism of trans fatty
      acids, and the scientific literature surrounding the effects of partially
      hydrogenated vegetable oils and trans fatty acids on blood cholesterol
      concentrations and cardiovascular disease risk.

PMID- 11458291
TI  - Interventional studies concerning the role of antioxidant vitamins in
      cardiovascular diseases: a review.
AB  - Cardiovascular diseases continue to constitute a major public health problem in
      all industrialized countries, where they are the main causes of premature
      mortality. There is a large body of evidence suggesting that free radical
      production directly or indirectly plays a major role in cellular processes
      implicated in atherosclerosis. Here we present mechanistic data and results of
      epidemiologic studies on the relationship between antioxidant vitamin intake or
      biochemical status and the risk of cardiovascular diseases. Most epidemiologic
      data obtained on this topic have been based on observational approaches, i.e.
      ecological studies, case-control or prospective studies. All these studies
      indicate that a high dietary intake or high blood concentrations of antioxidant
      vitamins are associated with a reduced risk of cardiovascular diseases. Although
      the results of these studies are convergent, they merely suggest a relationship
      at the population and individual level, but do not affirm a causality link. Only
      intervention studies (randomized trials), by specifically changing antioxidant
      vitamin intake, can provide conclusive answers. The apparent discrepancies
      between the results of recently published trials may be explained by the type of
      population (general or high-risk subjects), the differing doses of
      supplementation (nutritional levels or higher), the number of antioxidants tested
      (one, two or more) and the type of administration (alone or in balanced
      association). It thus appears that low risk of pathologies may be related to
      multiple nutrients consumed, at nutritional doses, and in combination. Optimal
      effects may be expected with a combination of nutrients at levels similar to
      those found in a healthy diet. A single antioxidant vitamin given at high doses
      in subjects with high risk of pathologies may not have substantial benefits and
      could even have negative consequences.

PMID- 11458292
TI  - Homocysteine, folic acid, B vitamins and cardiovascular risk.
AB  - Although there is considerable epidemiological evidence for a relationship
      between plasma homocysteine and cardiovascular disease, the role of homocysteine
      as a causal cardiovascular risk factor remains controversial. While results from
      high risk population based prospective studies generally support an association
      of elevated homocysteine levels with increased risk of cardiovascular disease,
      results from low risk population based prospective studies, however, tend to
      indicate a weaker association, or none at all. There is not yet any proof of a
      cardiovascular benefit mediated by folic acid plus B vitamins supplementation;
      nevertheless, some recent reports focusing on intermediate endpoints support the
      hypothesis of a benefit. Several interventional trials are underway and the
      answer of whether there is a cardiovascular benefit through folic acid plus B
      vitamins supplementation in different populations will be available in the years
      to come.

PMID- 11458293
TI  - Dietary protein and cardiovascular risk.
AB  - The relations between dietary protein and cardiovascular risk were first
      considered through their impact on blood cholesterol. Half a century after the
      first reports of an hypocholesterolemic effect of plant proteins, this subject is
      still a mater of debate, notably because of the difficulty in distinguishing
      between an independent effect of proteins and that of phytochemicals present in
      proteins preparations. In addition, many questions still have to be answered as
      to how the proteins may affect cholesterol metabolism. This review also describes
      the recent advances in new areas of research that have recently gained attention.
      Dietary proteins may affect cardiovascular risk through their effect on
      homocysteine, glutathione and nitric oxide. Although most of the data now
      available are still inconclusive, incoming results on these topics may prove
      important to appraise the role that the amount and/or the nature of dietary
      proteins play in the onset of cardiovascular disease.

PMID- 11458294
TI  - Non-cycloplegic screening for refractive errors in children with the hand-held
      autorefractor Retinomax: final results and comparison with non-cycloplegic
      photoscreening.
AB  - AIMS: To establish the results of refractive screening of preschool children with
      the hand-held autorefractor Retinomax under non-cycloplegic conditions, and to
      compare these results with those of photoscreening. METHODS: Among 1218 children
      undergoing non-cycloplegic refractive screening, 302 (25%) were also refracted
      under cycloplegia using the same refractor and were used as controls. Our
      criteria for a positive screening test were based on the spherical or cylinder
      values and were: myopia over 3D, astigmatism > or = 2D, spherical or cylindrical
      anisometropia > or = 1.5D, and hyperopia > or = 1.5D. Absolute myopia over 3D,
      absolute astigmatism > or = 2D, absolute anisometropia > or = 1.5D and absolute
      hyperopia > 3.5D were considered as true positives. The sensitivity, specificity,
      and positive and negative predictive values (PPV and NPV) were calculated within
      the group of controls for each refractive anomaly. On the basis of Bayes'
      theorem, these figures were then corrected to yield the true screening results
      that would be expected in a population without verification and selection bias.
      To determine the usefulness of this screening technique, the likelihood ratios
      for positive test results (+LR) were also calculated. The results of this
      screening in terms of sensitivity, specificity and predictive values were then
      compared with those of photoscreening. RESULTS: The basic results of screening
      with the hand-held autorefractor were as follows: -EHyperopia: sensitivity 46%,
      specificity 97%, PPV 55%, NPV 96%, +LR 15; -EAstigmatism: sensitivity 37%,
      specificity 99%, PPV 69%, NPV 96%, +LR 37; -EAnisometropia: sensitivity 66%,
      specificity 93%, PPV 19%, NPV 99%, +LR 9; -EMyopia: sensitivity 87%, specificity
      99%, PPV 33%, NPV 100%, +LR 87. The comparison with photoscreening revealed a
      similar performance when screening for hyperopia, but the hand-held autorefractor
      yielded much better figures when screening for astigmatism. In the case of myopia
      and anisometropia, the lack of consistent information concerning photoscreening
      invalidates any comparison. CONCLUSION: The hand-held autorefractor Retinomax
      appears to have potential as a screening device. Our experience with the non
      cycloplegic screening of preschool children for refractive anomalies indicates
      definite usefulness and reasonable accuracy of the Retinomax for detecting
      myopia, astigmatism and hyperopia. The weak point of this screening technique is
      the diagnosis of anisometropia, with only moderate utility and poor accuracy.

PMID- 11458295
TI  - Changes in refraction in anisomyopic patients.
AB  - PURPOSE: The purpose of this study was to investigate the evolution of refraction
      and visual function in patients with myopic anisometropia. DESIGN: A
      retrospective study on a selected population. METHODS: Forty-six anisomyopic
      patients underwent a complete ophthalmologic examination (cycloplegic refraction,
      visual acuity, ocular movement and fundus examination). RESULTS: The results show
      two different patterns of changes in refraction between the two eyes; in the same
      patient, the less myopic eye tends to get more myopic, while the more ametropic
      eye shows a more stable refraction. Furthermore, a recovery of binocular vision
      and amblyopia can be obtained by occlusion and full-time refractive correction.
      CONCLUSIONS: The evolution of refraction seems to be different in eyes with
      anisometropia and it is still to be understood whether it is fixation or reduced
      fixation that leads to a myopic shift.

PMID- 11458296
TI  - Botulinum toxin to the lateral rectus for the treatment of esotropia with
      paradoxical diplopia.
AB  - A retrospective review of six patients with paradoxical diplopia in the presence
      of esotropia was carried out. All patients were treated with botulinum toxin to
      the lateral rectus of the affected side. Five patients had no diplopia post toxin
      and the remaining patient had diplopia which could be ignored. The number of
      injections per patient ranged between 3 and 34. Three patients went on to have
      surgery to increase the angle of esotropia, with relief of diplopia. We conclude
      that botulinum toxin has a role in the treatment of esotropic patients with
      paradoxical diplopia.

PMID- 11458297
TI  - A comparative study of the effectiveness of disinsertion and anterior
      transposition of the inferior oblique in the treatment of unilateral superior
      oblique palsy.
AB  - PURPOSE: To compare the effectiveness of disinsertion of the inferior oblique
      muscle (DIO) with anterior transposition of the inferior oblique muscle (ATIO) in
      the treatment of vertical deviations resulting from superior oblique palsy.
      METHODS: In this prospective randomized study, 22 patients with unilateral
      superior oblique palsy were evaluated. Eleven patients underwent the DIO
      procedure (DIO group), and the other eleven underwent the ATIO procedure (ATIO
      group). Statistics were analyzed using the Wilcoxon and Mann-Whitney U tests.
      RESULTS: The mean preoperative primary-position hypertropia was 22.2 +/- 6.2
      prism diopters (Delta) in the DIO group and 23.1 +/- 6.6 Delta in the ATIO group;
      the mean preoperative hypertropia in adduction was 31.7 +/- 6.9 Delta in the DIO
      group and 31.8 +/- 8.1 Delta in the ATIO group. The mean follow-up was 18.8
      months (SD: 10.2, range: 6-40 months). The mean reduction of hypertropia in
      primary-position in the ATIO group (mean: 18.5 +/- 3.9 Delta) was found to be
      significantly greater than in the DIO group (mean: 13.3 +/- 1.9 Delta) (p =
      0.001). Even though the mean reduction of hypertropia in adduction in the ATIO
      group (mean: 27.7 +/- 9.6 Delta) was greater than in the DIO group (mean: 20.6 +/
      6.2 Delta), no statistically significant difference was found (p = 0.067). There
      was residual hypertropia in three (27.3%) patients who underwent the DIO
      procedure. No major postoperative complication was encountered in any of the
      patients. CONCLUSION: In vertical deviations resulting from superior oblique
      palsy, ATIO was found to be more effective than DIO in the reduction of primary
      position hypertropia.

PMID- 11458298
TI  - Strabismus surgery in congenital third nerve palsy.
AB  - BACKGROUND: Congenital third nerve palsy is a rare condition that usually
      presents with a large-angle incomitant strabismus and is often associated with
      ptosis and amblyopia. METHODS: We present the results of strabismus surgery in
      seven consecutive patients. RESULTS; All the palsies developed before the age of
      6 months and the age at surgery ranged from 3 to 24 years. The operations
      performed included horizontal recti resection/recession (7), supra-placement of
      the insertions (6), superior oblique weakening (4) and traction sutures (4). The
      preoperative and postoperative horizontal deviations consisted of seven
      exotropias and one esotropia due to a combined sixth and partial third nerve
      palsy. The preoperative vertical deviation consisted of 7 hypotropias and one
      hypertropia; postoperatively, 5 remained hypotropic and 2 were hypertropic. All
      patients underwent ptosis surgery. CONCLUSION: Patients with congenital third
      nerve palsy often achieve reasonable cosmesis with strabismus and ptosis surgery.

PMID- 11458299
TI  - Assortative mating in the affective disorders: a systematic review and meta
      analysis.
AB  - Assortative mating, or the tendency for individuals with similar phenotypes to
      mate more frequently than expected by chance, has been reported for a variety of
      complex traits, including many neuropsychiatric disorders. Although assortative
      mating has been reported in affective disorders, the studies done to date have
      been inconclusive. This study attempts to assess the degree of assortative mating
      in individuals with affective disorders using systematic review and meta-analytic
      techniques. Studies on assortative mating in affective disorders were identified
      by a computerized literature search and by bibliographic assessment of published
      studies and reviews. Studies were selected if they had a case-control design and
      if they reported rates of affective disorders in the spouses of probands and
      controls. Of the 17 studies reviewed, six were selected for meta-analysis. All
      studies were blinded. Details of study design, patient characteristics, and rates
      of affective disorders were assessed by two independent reviewers. Twelve of the
      17 studies assessed reported an increase in assortative mating. Results of the
      meta-analysis supported these findings, and indicated that assortative mating
      occurs in both bipolar disorder and major depression. Although most studies
      examined reported an increase in assortative mating among individuals with
      affective disorders, the degree of assortative mating reported varied widely.
      Meta-analysis with six controlled studies showed evidence for assortative mating,
      and suggested that the degree of assortative mating is higher for individuals
      with bipolar disorder than for those with major depression. These results support
      the previously reported findings, and may have important implications for genetic
      studies.

PMID- 11458300
TI  - Determinants of risk behavior for human immunodeficiency virus/acquired
      immunodeficiency syndrome in people with severe mental illness.
AB  - We examined the prevalence and correlates of human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome (AIDS) risk behaviors in a large sample
      of severely mentally ill (SMI) patients. Risk levels were correlated with
      demographic factors, diagnosis, symptom severity, trauma history, post-traumatic
      stress disorder (PTSD), substance use disorder (SUD), and sexual orientation. SMI
      clients from urban and rural settings (N = 275) were assessed regarding HIV/AIDS
      risk behaviors, and hypothesized risk factors. Patients exhibited substantial
      levels of risky behavior, particularly sexual risk. Correlates of increased risk
      included SUD, trauma, male homosexual orientation, younger age, and symptom
      severity. Structural equation modeling identified SUD and sexual orientation as
      the primary determinants of both drug and sexual risk behavior. We conclude that
      specific illness related variables appear to have less impact on risk behavior
      among people with SMI than previously hypothesized. Substance abuse prevention
      and treatment may be the most effective means of reducing HIV risk in this
      population.

PMID- 11458301
TI  - The adult antisocial syndrome with and without antecedent conduct disorder:
      comparisons from an adoption study.
AB  - DSM antisocial personality disorder (ASPD) requires a retrospective diagnosis of
      conduct disorder-historical behavior not present in everyone with adult ASPD
      criteria. Using adoption study data, we examined the impact of this requirement
      on biological and environmental risk associations. We also compared clinical
      correlates of adult antisocial behavior with and without prior conduct disorder.
      We defined three subgroups: DSM-III ASPD (n = 30), adult antisocials without
      conduct disorder (n = 25), and controls (n = 142). By design, the sample had a
      high incidence of biological parent ASPD, which was partially confounded with
      fetal alcohol exposure. We compared the associations of both of these putative
      risk factors with subgroup membership after controlling for gender and adverse
      adoptive environment. We also examined differences in two sociopathy scales and
      the incidence of co-occurring affective, alcohol, and other substance use
      disorders. Finally, we explored differences in individual antisocial symptoms.
      Having an antisocial biological parent was a specific risk factor for ASPD. In
      contrast, fetal alcohol exposure, male gender, and adverse environment were
      associated with the adult antisocial syndrome, regardless of conduct disorder
      history. The two antisocial groups were similar with respect to sociopathy
      scales, co-occurring diagnoses, and the incidence of most individual symptoms.
      However, several adult and conduct disorder symptoms had significant specific
      associations with biological or environmental background or their interaction.
      Phenotypic expression of the biological-possibly genetic-risk for ASPD appears to
      be manifest before adulthood. The influence of other risk factors may not depend
      on antecedent conduct disorder. Despite this, we could not detect clinically
      important differences between the two sociopathic groups. The conduct disorder
      requirement therefore may be more relevant to etiological than clinical
      understanding of adult antisocial behavior.

PMID- 11458302
TI  - Correlates of community violence exposure in hospitalized adolescents.
AB  - To examine psychological and behavioral correlates of community violence exposure
      in psychiatrically hospitalized adolescents, 89 inpatients were administered a
      battery of psychometrically well-established self-report instruments. Violence
      exposure was assessed using the Child's Exposure to Violence Checklist (CEVC).
      Half of the patients reported exposure to multiple incidents violence in their
      community (52%) and home (53%). Sixty-one percent were victims of physical
      assault, and 39% were victims of sexual assault. Patients who had witnessed
      community violence reported significantly more post-traumatic stress disorder
      (PTSD) symptoms, drug use, and violence potential than patients without a history
      of witnessing community violence. Patients exposed to community violence were
      also more likely to be the victim of childhood maltreatment, as well as a
      perpetrator of violence. In conclusion, traumatization via exposure to community
      violence may serve as one important determinant in the development of mixed
      internalizing and externalizing psychopathology in adolescent inpatients, thus
      necessitating accurate assessment and treatment planning.

PMID- 11458303
TI  - Comparison of obsessive-compulsive disorder patients with and without comorbid
      putative obsessive-compulsive spectrum disorders using a structured clinical
      interview.
AB  - Increasing attention has been paid to the possibility that a range of disorders,
      the putative obsessive-compulsive spectrum disorders (OCSDs), may share
      overlapping phenomenological and neurobiological features with obsessive
      compulsive disorder (OCD). The development of a structured clinician-administered
      interview for the putative OCSDs (SCID-OCSD) is described. This instrument was
      used to investigate differences between OCD patients with a comorbid putative
      OCSD and OCD patients without a comorbid putative OCSD. A sample of 85 adult
      patients (38 men and 47 women) presenting for treatment of OCD was interviewed
      with the SCID-OCSD. OCD patients without comorbid putative OCSDs (n = 36) were
      compared to patients with comorbid OCSDs (n = 49) in terms of demographic
      features, clinical characteristics, and associated comorbidity with other non
      OCSD DSM-IV axis I disorders. Of the OCD patients, 57.6% currently met criteria
      for at least one putative OCSD and 67.1% had a lifetime history of at least one
      comorbid OCSD. The OCSDs with the highest prevalence rates were compulsive self
      injury (22.4%), compulsive buying (10.6%), and intermittent explosive disorder
      (10.6%). There was a significantly larger proportion of women in the group with
      comorbid OCSDs. Although the two groups did not differ in terms of severity of
      OCD symptoms, the group with comorbid OCSDs had significantly more obsessions and
      compulsions. The two groups did not differ significantly in terms of associated
      psychopathology other than OCSDs. We conclude that the SCID-OCSD provides
      clinicians and researchers with an instrument for the diagnosis of putative
      OCSDs. Our findings suggest that putative OCSDs have a relatively high prevalence
      rate in OCD patients. In addition, OCD patients with comorbid OCSDs differ with
      regard to certain demographic and clinical features. Further research,
      particularly genetic and neuroimmunological work, may ultimately be useful in
      validating the obsessive-compulsive spectrum.

PMID- 11458304
TI  - Gender differences in a sample of schizophrenic outpatients.
AB  - Our objective was to study gender differences in schizophrenia, comparing
      clinical, social, and illness course characteristics. A sample of 239
      schizophrenic (DSM-IV criteria) outpatients were administered the following
      instruments: service use and demographic questionnaires, the Positive and
      Negative Symptom Scale (PANSS), the Disability Assessment Scale (DAS), and the
      Global Assessment of Functioning (GAF) scale. The female to male ratio was 1/2.
      Men had an earlier age at onset. Women were more likely to be married and to live
      independently, and there were more unemployed men. Social functioning was
      slightly better in women (lower DAS scoring). No differences were found in
      symptomatological variables (global or separate PANSS scales), nor in type of
      schizophrenia. Course of illness in the past year appeared to be similar, except
      for longer hospital stays in men. We conclude that schizophrenic women had a
      significantly better social functioning, despite the lack of remarkable
      symptomatic differences between genders.

PMID- 11458305
TI  - The convergence of neuropsychological testing and clinical ratings of cognitive
      impairment in patients with schizophrenia.
AB  - This study examined the relationship between clinical rating of cognitive
      symptoms and performance on neuropsychological tests in acute and chronic samples
      of patients with schizophrenia. Two separate studies examined patients who varied
      widely in their lifetime functional outcome, including 263 elderly poor-outcome
      inpatients and 20 acutely admitted patients. In the first study, six cognitive
      performance measures were collected, and in the second study, five different
      measures were collected. Correlations with different symptom models of cognitive
      and negative symptoms were examined. In both samples, cognitive symptoms were
      never more highly correlated with cognitive test performance than with negative
      symptoms. When cognitive and negative symptom ratings were combined, they never
      accounted for as much as half of the variance in performance on the cognitive
      tests in both samples. These data suggest that clinical assessment of symptoms is
      not a viable alternative to neuropsychological testing to obtain information
      about cognitive functioning in schizophrenia. These results may also be specific
      to the clinical rating scale used, the Positive and Negative Syndrome Scale
      (PANSS).

PMID- 11458306
TI  - Depression in patients with schizophrenia during an acute psychotic episode.
AB  - There is disagreement about whether depressive symptoms in schizophrenia are part
      of the basic disease process, or whether they represent adverse effects of
      treatment with antipsychotic medications. In a sample of initially antipsychotic
      drug-free acutely hospitalized patients with schizophrenia (N = 104), we measured
      change in depressive symptoms after 4 weeks of treatment. We also examined the
      relationship of changes in depressive symptoms to changes in positive and
      negative schizophrenic symptoms. Depressive symptoms improved after 4 weeks of
      antipsychotic medication treatment, and their improvement corresponded with
      improvement in both positive and negative schizophrenic symptoms. These results
      suggest that depressive symptoms in schizophrenia are related to the disease
      process itself, at least during acute exacerbations of schizophrenia. Depressive
      symptoms may be responsive to antipsychotic medications directly or as a
      secondary response to improvement in positive and negative symptoms.

PMID- 11458307
TI  - Children and adolescents with psychotic disorder not otherwise specified: a 2- to
      8-year follow-up study.
AB  - Although psychotic phenomena in children with disruptive behavior disorders are
      more common than expected, their prognostic significance is unknown. To examine
      the outcome of pediatric patients with atypical psychoses, a group of 26 patients
      with transient psychotic symptoms were evaluated with clinical and structured
      interviews at the time of initial contact (mean age, 11.6 +/- 2.7 years) and at
      follow-up 2 to 8 years later. Measures of functioning and psychopathology were
      also completed at their initial assessment. Risk factors associated with adult
      psychotic disorders (familial psychopathology, eyetracking dysfunction in
      patients and their relatives, obstetrical complications, and premorbid
      developmental course in the proband) had been obtained at study entry. On follow
      up examination (mean age, 15.7 +/- 3.4 years), 13 patients (50%) met diagnostic
      criteria for a major axis I disorder: three for schizoaffective disorder, four
      for bipolar disorder, and six for major depressive disorder. The remaining 13
      patients again received a diagnosis of psychotic disorder not otherwise specified
      (NOS), with most being in remission from their psychotic symptoms. Among this
      group who had not developed a mood or psychotic disorder, disruptive behavior
      disorders were exceedingly common at follow-up and were the focus of their
      treatment. Higher initial levels of psychopathology, lower cognitive abilities,
      and more developmental motor abnormalities were found in patients with a poor
      outcome. Obstetrical, educational, and family histories did not differ
      significantly between the groups. Through systematic diagnostic evaluation,
      children and adolescents with atypical psychotic disorders can be distinguished
      from those with schizophrenia, a difference with important treatment and
      prognostic implications. Further research is needed to delineate the course and
      outcome of childhood-onset atypical psychoses, but preliminary data indicate
      improvement in psychotic symptoms in the majority of patients and the development
      of chronic mood disorders in a substantial subgroup.

PMID- 11458308
TI  - The retrospective assessment of childhood attention deficit hyperactivity
      disorder in adults: reliability and validity of the Italian version of the Wender
      Utah Rating Scale.
AB  - To assess the reliability and validity of the Wender Utah Rating Scale (WURS),
      759 Italian undergraduate students were administered the Italian version of the
      WURS. In this sample, the WURS showed good internal consistency reliability
      (Cronbach alpha =.888). Both 1-week (r =.981, P <.001) and 2-month (r =.924, P
      <.001) retest reliabilities were satisfactory. The mother/subject agreement on
      the WURS total score was large: intraclass r =.883, P <.001. The principal
      component (PC) analysis showed the presence of three positively correlated first
      order PCs, and one second-order PC. This PC structure of the WURS was replicated
      in an independent sample of 300 consecutively admitted psychiatric inpatients and
      outpatients. Finally, in a sample of 132 secondary school students, the WURS
      showed a moderate correlation with the Conners Abbreviated Parent and Teacher
      Questionnaire (CAPTQ): r =.307, P <.001. In this sample, the WURS total score was
      negatively correlated with school performance (rho = -.460, P <.001) and conduct
      (rho = -.293, P <.005) indexes.

PMID- 11458309
TI  - Factor validity of the temperament and character inventory in patients with major
      depression.
AB  - Cloninger has proposed a seven-factor psychobiological model of personality and
      has developed the Temperament and Character Inventory (TCI) to measure four
      temperament dimensions and three character dimensions. This theory of personality
      may be of great importance in developing an integrated understanding of
      psychosocial and biological processes underlying the etiology and course of
      depression, and a large number of studies are being carried out using the TCI to
      determine the pathology of depression. The present study investigated the factor
      validity of the TCI in 156 mildly to moderately depressed patients with major
      depression. The results indicate that the TCI is an internally consistent and
      factor-analytically valid instrument in patients. Although there was some
      evidence that a state of depression strengthened correlation between harm
      avoidance and cooperativeness, the proposed factor structure of the TCI appeared,
      in general, robust against the state effect of depression, when the state was
      mild to moderate. These results suggested that the TCI has considerable promise
      as an instrument for characterizing the underlying personality structure of
      mildly to moderately depressed patients with major depression.

PMID- 11458312
TI  - Pregnant and homeless: the resiliency of the human spirit.

PMID- 11458313
TI  - Age-related vision loss in the older adult: the role of the nurse practitioner in
      prevention and early detection.
AB  - Vision loss is a common problem in older adults and may result in functional
      impairment and accidental injury. The four most common causes of vision loss in
      this age group are age-related macular degeneration, cataracts, glaucoma, and
      diabetic retinopathy. The nurse practitioner has an important role in the
      prevention and early detection of these conditions. This article reviews
      scientific evidence on risk factors and preventative interventions for the causes
      of age-related vision loss. It also describes the important role of the nurse
      practitioner in assessment of eye health, so that conditions that may be damaging
      to vision may be detected early and monitored in the primary care setting.

PMID- 11458314
TI  - Clinical breast examination: an illustrated educational review and update.
AB  - A nurse practitioner educator and a physician educator, experts in teaching
      clinical breast examination techniques, review the essential steps of the
      procedure and emphasize breast cancer detection. Photographs show each step of
      the procedure.

PMID- 11458315
TI  - Evaluation and management of the patient co-infected with human immunodeficiency
      virus and hepatitis C.
AB  - The emerging presence of hepatitis C viral (HCV) infection in the United States
      has been the focus of much attention among health care providers and the general
      population. Among patients infected with human immunodeficiency virus (HIV),
      there has been a dramatic increase in hepatitis C disease. During the 1980s and
      early 1990s, hepatitis C was viewed as a disease for which little could be done,
      both because of ineffective treatment and the severity and lack of adequate
      treatments for acquired immune deficiency syndrome (AIDS) itself. Treatment with
      interferon had poor effect on hepatitis C in the co-infected population,
      especially for those with advanced immunosuppression. The regimen was difficult
      to tolerate even with dose reductions. With the advent of highly active
      antiretroviral therapy (HAART) and effective treatment and prophylaxis for
      opportunistic infections, a substantial portion of HIV-infected patients are
      living long enough to have their health compromised by hepatic failure or
      hepatocellular carcinoma owing to hepatitis C, rather than by AIDS-related
      illness. New treatments are available for hepatitis C, with preliminary research
      yielding promising results. The role of these medications in managing HIV/HCV co
      infection is currently under study, with implications for many. Health care
      providers are increasingly faced with the challenges of caring for people
      infected with the hepatitis C virus, and the growing number of individuals co
      infected with hepatitis C and HIV. The purpose of this article is to provide an
      overview of hepatitis C, especially in the presence of HIV infection, and to
      detail the recognition and management of the care of this emerging population.

PMID- 11458316
TI  - Managing constipation in a pediatric patient: it is more than a simple problem.
AB  - The purpose of this article is to illustrate the complexities of care of a
      toddler with constipation. When a child presents to the primary care clinic,
      there is the child, the significant caregiver(s), and the family as the patients.
      Hence, what may appear on the surface as an easy to manage (and therefore quick)
      problem may not be so. In today's productivity cost-driven health care system,
      the primary care provider is challenged to provide comprehensive safe care.
      Rationale and evidence link the elements of the case to demonstrate that this is
      not such a simple problem.

PMID- 11458317
TI  - Perceived barriers to rural nurse practitioner practice.
AB  - Studies of barriers to nurse practitioner (NP) practice show similar results for
      more than 20 years. Comparisons of barriers to rural NP practice have not been
      performed. Descriptive data about perceived barriers to practice were collected
      from 292 NPs in one midwestern state (urban, 229; rural, 63; response rate, 60%).
      A primary barrier was a lack of understanding by the general public about the NP
      role, which respondents found was detrimental to practice success. Physicians
      also lacked knowledge about the NP role. Rural practice barriers also included
      lack of peer support, suggesting that isolation from other NPs detracted from
      practice success. Educating the public and health professionals about NP
      education, scope of practice, and roles continues to be necessary. Media
      campaigns can increase understanding of NP practice. Rural NPs can use electronic
      means to communicate with each other to decrease practice isolation. Removing
      barriers to practice remains an ongoing task to enhance rural nursing practice.

PMID- 11458318
TI  - Nurses' and physicians' views about euthanasia.
AB  - Nurses' and physicians' views about euthanasia were investigated using a
      questionnaire that was answered by 113 nurses and 83 physicians in the internal
      medicine and surgery inpatient services of Hacettepe University Adult Hospital,
      Ankara, Turkey. The data were evaluated with Chi-square statistical test and
      percentages. The study results showed that both nurses and physicians define
      euthanasia as "a person's right to die." Nurses responded that euthanasia may be
      appropriate with terminally ill elderly patients; however, physicians responded
      that it may be appropriate with patients at any age who are in the last stage of
      a terminal illness. Although both groups accepted euthanasia conditionally, they
      stressed that, in practice, the primary responsibility should be with patients
      and their relatives. When faced with a patient who wishes a painless death,
      nurses said that they feel helpless, anxious and guilty, and find themselves in a
      dilemma. However, physicians responded that they feel satisfied that they are
      doing the right thing in continuing the patient's medical therapy.

PMID- 11458319
TI  - Understanding managed care: practice implications for NPs.
AB  - Highly effective nurse practitioners in managed care settings may understand the
      basic concept of managed care without appreciating how the context of managed
      care impacts their practice. This article discusses the concept of managed care
      within the context of 4 managed care strategies. In developing this paper, our
      goals were first, to describe contracts, incentives, management, and medical
      necessity as managed care strategies and second, to discuss some of the ways
      these strategies can significantly impact nurse practitioner practice.
      Illustrative practice examples are used to suggest that those nurse practitioners
      who understand managed care, both as a theoretical concept and as a context for
      practice, may find that they are better able to develop innovative ways to meet
      the needs of their patients.

PMID- 11458320
TI  - An advanced practice international health initiative: the Ghana Health Mission.
AB  - Nursing faculty members are responsible for meeting service, teaching,
      scholarship, and developing international relations requirements for tenure and
      promotion in most universities. The profession of nursing requires that nursing
      faculty, especially nurse practitioner faculty, maintain clinical excellence and
      prepare culturally competent graduates. The question remains, how can we do it
      all? A unique, advanced practice, international health initiative in Ghana West
      Africa was developed to help provide health promotion to a community in need. It
      has evolved into a project that has facilitated the achievement of those
      aforementioned requirements of university faculty.

PMID- 11458323
TI  - Stem cells and cloning: The fuss, revisited.

PMID- 11458324
TI  - AAA award winners.

PMID- 11458325
TI  - A.J. Ladman AAA/Wiley Exemplary Service Award.

PMID- 11458326
TI  - Reevaluating digital vs. conventional photographic cameras for research.

PMID- 11458328
TI  - Adult stem cells and neurogenesis: historical roots and state of the art.
AB  - Over the last few years, an impressive number of papers have addressed the stem
      cell issue. However, as often occurs when a scientific subject undergoes a period
      of fast growth, some confusion is generated. To help reduce the existing
      uncertainty, this paper focuses on the concept of adult stem cells in relation to
      the classification of cell populations on the basis their proliferative behavior.
      Particular attention is dedicated to adult neural stem cells, an issue that has
      recently seen the most amazing advances. Finally, the concept of adult stem cells
      is differentiated from that of developmental stem cells in relation to the
      employment of stem cells for transplantation therapies.

PMID- 11458329
TI  - Basic and clinical neuroscience applications of embryonic stem cells.
AB  - There have been recent dramatic advances in our understanding of the molecular
      mechanisms governing the elaboration of mature tissue-specific cellular
      subpopulations from embryonic stem (ES) cells. These investigations have
      generated a range of new biological and potential therapeutic reagents to allow
      us to dissect specific stages of mammalian development that were previously
      experimentally inaccessible. Ultimately, we will be able to reconstitute seminal
      signaling pathways to promote regeneration of the nervous system. Totipotent ES
      cells possess an unlimited proliferative capacity that make them attractive
      candidates for use in a series of innovative transplantation paradigms.
      Elucidation of the molecular and physiologic properties of ES cells also has
      important implications for our understanding of the integrative cellular
      processes underlying neural induction, patterning of the neural tube, neural
      lineage restriction and commitment, neuronal differentiation, regional neuronal
      subtype specification, and the specific pathological consequences of alterations
      in discrete components of these fundamental neurodevelopmental pathways. In
      addition, recent experimental observations suggest that neurodegenerative disease
      pathology may involve alterations in a range of progressive neural inductive and
      neurodevelopmental events through novel biological mechanisms that result in
      sublethal impairments in cellular homeostasis within evolving regional neuronal
      precursor populations containing the mutant proteins, culminating in increased
      vulnerability of their differentiated neuronal progeny to late-onset apoptosis.
      Future discoveries in ES cell research will offer unique conceptual and
      therapeutic perspectives that representing an alternative to neural stem cell
      therapeutic strategies for ameliorating the pathologic consequences of a broad
      range of genetic and acquired insults to the developing, adult, and aging brain.
      Evolving regenerative strategies for both neurodevelopmental and
      neurodegenerative diseases will likely involve the targeting of vulnerable
      regional neural precursor populations during "presymptomatic" clinicopathological
      stages prior to the occurrence of irrevocable neural cell injury and cell death.

PMID- 11458330
TI  - Controlled and complete release of a model poorly water-soluble drug,
      prednisolone, from hydroxypropyl methylcellulose matrix tablets using (SBE)(7m)
      beta-cyclodextrin as a solubilizing agent.
AB  - Sustained-release formulations such as hydroxypropyl methylcellulose (HPMC)-based
      hydrophilic matrix tablets of poorly water-soluble drugs often result in
      incomplete release because of the poor solubility and dissolution rate of the
      drug in the hydrophilic matrix. Sulfobutylether-beta-cyclodextrins ((SBE)(7M)
      beta-CDs) have been known to improve the solubility of such drugs by forming
      inclusion complexes. The present paper deals with the modification of drug
      release from an HPMC-based matrix tablet of a sparingly water-soluble drug,
      prednisolone (PDL), using (SBE)(7M)-beta-CD as a solubilizing agent. Tablets were
      prepared by direct compression of a physically mixed PDL, (SBE)(7M)-beta-CD, and
      polymer. On exposure to water, an in situ PDL:(SBE)(7M)-beta-CD complex was
      formed in the gel layer, and enhanced drug release relative to a control
      formulation was observed (lactose used as the excipient instead of (SBE)(7M)-beta
      CD ). Other possible changes due to the incorporation of (SBE)(7M)-beta-CD in the
      formulation were also probed. Incorporation of (SBE)(7M)-beta-CD lead to a higher
      water uptake relative to the control (lactose) formulation. For a fixed total
      tablet weight, polymer type, and loading, the drug release rate appeared to
      depend on the molar ratio of (SBE)(7M)-beta-CD to PDL and not the absolute amount
      of (SBE)(7M)-beta-CD present in the matrix tablet. This work shows that
      incorporation of (SBE)(7M)-beta-CD into the matrix tablets could be considered in
      designing a sustained-release tablet of poorly water-soluble drugs.

PMID- 11458331
TI  - High-performance liquid chromatography determination of hydrastine and berberine
      in dietary supplements containing goldenseal.
AB  - Goldenseal (Hydrastis canadensis L., Ranunculaceae) is an ingredient of various
      dietary supplements intended for enhancing general body immunity. Many goldenseal
      products are currently available in the United States, either alone or in
      combination with echinacea. In most products, the content of the main active
      alkaloids of goldenseal, hydrastine and berberine, is not indicated on the label.
      A high-performance liquid chromatography (HPLC) method has been developed for the
      detection and quantification of hydrastine and berberine in a number of products
      obtained from the United States market. The method uses a Phenomenex Luna C(18)
      column, a mobile phase consisting of solvent A (100 mM sodium acetate/acetic
      acid, pH 4.0) and solvent B (acetonitrile/methanol; 90/10, v/v). Elution was run
      at a flow rate of 1.0 mL/min, with a linear gradient of 80- 40% A in B over 20
      min and ultraviolet detection at 290 nm. A wide range of content variation was
      observed for both alkaloids in the tested samples.

PMID- 11458332
TI  - The bulk crystallization of alpha-lactose monohydrate from aqueous solution.
AB  - The bulk crystallization of alpha-lactose monohydrate from aqueous solution by
      primary nucleation has been studied under controlled conditions of
      supersaturation, temperature, and pH. The induction times to nucleation were
      extremely long compared with those generally observed for other materials, even
      at the high supersaturations used in the experiment. As a result, it was
      necessary to stir the supersaturated solution vigorously to induce nucleation in
      a reasonable but still lengthy working time. Even then, nucleation only occurred
      to a limited extent, following which growth ceased for 8-10 h before resuming.
      After this period, growth recommenced but again slowed to a low rate after
      another 8 h. At this stage, the yield of product was low and in most cases the
      particles had achieved sizes close to the maximum noted. The yields increased
      with further crystallization time (22-72 h total from the recommencement of
      growth) to give, under high initial supersaturation conditions, amounts of
      product close to the theoretical value. For the most part, however, the particle
      size did not increase with this later increase in yield, showing only significant
      changes after the extremely long total crystallization times. It is proposed that
      these extreme properties result from the formation in solution by mutarotation of
      the anomer alpha-lactose, which inhibits nucleation as well as its previously
      observed influence on growth.

PMID- 11458333
TI  - Liquid chromatography/mass spectrometry (LC/MS) identification of photooxidative
      degradates of crystalline and amorphous MK-912.
AB  - How and why the chemical stability of amorphous solid is different from
      crystalline solid is an important problem. In this study, this problem is
      addressed by evaluation of the photodegradation of both crystalline and amorphous
      MK-912 (an alpha-2 adrenoceptor antagonist) according to the photostability tests
      of the ICH (International Conference on Harmonization) guidelines. Under the ICH
      conditions, the photodegradation rate of the amorphous MK-912 was approximately
      40 times faster than that of the crystalline MK-912. The photodegradation yielded
      isomeric, oxidative degradates. Three keto-degradates (molecular weight of 14 Da
      over MK-912) were observed for both forms. But, whereas five alcohol and one N
      oxide degradates (molecular weight of 16 Da over MK-912) were observed for the
      amorphous form, only one alcohol degradate was observed for the crystalline form.
      Liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS were applied to
      identify these low-level photodegradates. A thorough analysis of the MS/MS data
      of protonated MK-912 was the key to the identification, and the special MS/MS
      features of the degradates due to the structural modifications from degradations
      were also important. Following this strategy, the structures of all the
      photodegradates were proposed. The structural identification of the
      photodegradates of MK-912 shed light on the different photostabilities between
      the crystalline and amorphous MK-912.

PMID- 11458334
TI  - Dehydration, hydration behavior, and structural analysis of fenoprofen calcium.
AB  - Fenoprofen calcium (FC) is a nonsteroidal, anti-inflammatory, analgesic, and
      antipyretic agent. The dehydration behavior of FC dihydrate and the rehydration
      of the dried FC were investigated using differential scanning calorimetry (DSC),
      thermogravimetric analysis (TGA), and powder X-ray diffractometry (PXRD). The
      stoichiometry, the crystal packing arrangement, and water environments in FC
      dihydrate were determined using single-crystal X-ray diffraction (XRD) analysis.
      The Arrhenius plot (natural logarithm of the dehydration rate constant versus the
      reciprocal of absolute temperature) for FC dihydrate from isothermal TGA is not
      linear. The activation energy of dehydration was 309 kJ/mol in the 50-60 degrees
      C range and 123 kJ/mol in the 60-80 degrees C range. The difference in activation
      energy can be explained from the crystal structure data where one water molecule
      is sandwiched between repeating polar carboxylate groups and the other water is
      in a slightly less polar region of the crystal. Single-crystal XRD analysis also
      indicated each calcium ion is coordinated to six oxygens. Two coordinating
      oxygens are provided by two water molecules and the other four oxygens are
      provided by the carboxylate group of four separate fenoprofen anions. Each
      fenoprofen anion, which can provide two oxygens for coordination, is associated
      with two different calcium ions. Hot-stage PXRD suggested that only a loss of 1
      mole of water per mole of FC dihydrate (forming a monohydrate) was required to
      convert the material to a partially crystalline state. The monohydrate is not
      completely disordered as evidenced by a strong diffraction peak as well as some
      weaker peaks in the PXRD pattern. The rehydration of the anhydrous form of FC
      follows a solution-mediated transformation, prior to crystallizing as the
      dihydrate.

PMID- 11458335
TI  - The ice nucleation temperature determines the primary drying rate of
      lyophilization for samples frozen on a temperature-controlled shelf.
AB  - The objective of this study was to determine the influence of ice nucleation
      temperature on the primary drying rate during lyophilization for samples in vials
      that were frozen on a lyophilizer shelf. Aqueous solutions of 10% (w/v)
      hydroxyethyl starch were frozen in vials with externally mounted thermocouples
      and then partially lyophilized to determine the primary drying rate. Low- and
      high-particulate-containing samples, ice-nucleating additives silver iodide and
      Pseudomonas syringae, and other methods were used to obtain a wide range of
      nucleation temperatures. In cases where the supercooling exceeded 5 degrees C,
      freezing took place in the following three steps: (1) primary nucleation, (2)
      secondary nucleation encompassing the entire liquid volume, and (3) final
      solidification. The primary drying rate was dependent on the ice nucleation
      temperature, which is stochastic in nature but is affected by particulate content
      and the presence of ice nucleators. Sample cooling rates of 0.05 to 1 degrees
      C/min had no effect on nucleation temperatures and drying rate. We found that the
      ice nucleation temperature is the primary determinant of the primary drying rate.
      However, the nucleation temperature is not under direct control, and its
      stochastic nature and sensitivity to difficult-to-control parameters result in
      drying rate heterogeneity. Nucleation temperature heterogeneity may also result
      in variation in other morphology-related parameters such as surface area and
      secondary drying rate. Overall, these results document that factors such as
      particulate content and vial condition, which influence ice nucleation
      temperature, must be carefully controlled to avoid, for example, lot-to-lot
      variability during cGMP production. In addition, if these factors are not
      controlled and/or are inadvertently changed during process development and
      scaleup, a lyophilization cycle that was successful on the research scale may
      fail during large-scale production.

PMID- 11458336
TI  - Annealing to optimize the primary drying rate, reduce freezing-induced drying
      rate heterogeneity, and determine T(g)' in pharmaceutical lyophilization.
AB  - In a companion paper we show that the freezing of samples in vials by shelf-ramp
      freezing results in significant primary drying rate heterogeneity because of a
      dependence of the ice crystal size on the nucleation temperature during
      freezing.1 The purpose of this study was to test the hypothesis that post
      freezing annealing, in which the product is held at a predetermined temperature
      for a specified duration, can reduce freezing-induced heterogeneity in
      sublimation rates. In addition, we test the impact of annealing on primary drying
      rates. Finally, we use the kinetics of relaxations during annealing to provide a
      simple measurement of T(g)', the glass transition temperature of the maximally
      freeze-concentrated amorphous phase, under conditions and time scales most
      appropriate for industrial lyophilization cycles. Aqueous solutions of
      hydroxyethyl starch (HES), sucrose, and HES:sucrose were either frozen by
      placement on a shelf while the temperature was reduced ("shelf-ramp frozen") or
      by immersion into liquid nitrogen. Samples were then annealed for various
      durations over a range of temperatures and partially lyophilized to determine the
      primary drying rate. The morphology of fully dried liquid nitrogen-frozen samples
      was examined using scanning electron microscopy. Annealing reduced primary drying
      rate heterogeneity for shelf-ramp frozen samples, and resulted in up to 3.5-fold
      increases in the primary drying rate. These effects were due to increased ice
      crystal sizes, simplified amorphous structures, and larger and more numerous
      holes on the cake surface of annealed samples. Annealed HES samples dissolved
      slightly faster than their unannealed counterparts. Annealing below T(g)' did not
      result in increased drying rates. We present a simple new annealing
      lyophilization method of T(g)' determination that exploits this phenomenon. It
      can be carried out with a balance and a freeze-dryer, and has the additional
      advantage that a large number of candidate formulations can be evaluated
      simultaneously.

PMID- 11458337
TI  - Fourier transform Raman spectroscopic study of the interaction of water vapor
      with amorphous polymers.
AB  - Water associated with amorphous polymers is known to affect their chemical and
      physical properties. The purpose of this study was to investigate the nature of
      water-polymer interactions for some polymers of pharmaceutical interest. Using
      Raman spectroscopy, polymer-water hydrogen bond interactions were probed for two
      molecular weight grades of poly(vinylpyrrolidone), namely PVP K90 and PVP K12,
      and also for poly(vinylacetate) and poly(vinyl pyrrolidone-co-vinyl acetate).
      Water vapor absorption isotherms were obtained for the polymers, and the effect
      of the absorbed water on the glass transition temperature was determined. A
      knowledge of the water content and physical state of the polymer was used to aid
      interpretation of Raman spectral changes. The strength of the hydrogen bond
      formed with water was found to depend on the chemistry of the polymer, with the
      pyrrolidone group interacting more strongly than the acetate group. However,
      minor differences were also observed between the degree of interaction of water
      and polymer for PVP K12 and PVP K90 at some water contents. This result is
      attributed to differences in the structural relaxation changes accompanying
      plasticization by water for the two molecular weight grades. Using principal
      components analysis of the spectral data, it was also possible to differentiate
      between samples in the rubbery state and samples in the glassy state. In
      conclusion, water sorbed into polymers causes changes in the polymer Raman
      spectra not only because of hydrogen bonding, but also as a result of the
      plasticizing effect of water on polymer mobility.

PMID- 11458338
TI  - Formulation and characterization of amphotericin B-polyethylenimine-dextran
      sulfate nanoparticles.
AB  - A new aqueous nanoparticle system has been developed using complex coacervation
      employing the oppositely charged polymers polyethylenimine (PEI) and dextran
      sulfate (DS), with zinc sulfate as a stabilizing agent. Amphotericin B (AmB) was
      loaded into the nanoparticles as a model drug. The nanoparticles contained PEI
      and DS in the weight ratio of approximately 1:2. They possessed a zeta potential
      of approximately +30 mV and demonstrated a narrow size distribution in the range
      100-600 nm with a polydispersity index of 0.2. Electron microscopy revealed
      spherical nanocapsules with a smooth surface. Very favorable drug entrapment and
      recovery efficiencies of up to 85% were routinely observed. Processing
      parameters, such as the pH of the PEI solutions, ratio of the two polymers, as
      well as the concentrations of DS and zinc sulfate, all played a significant role
      in controlling particle size. Dissolution studies demonstrated a fast release
      that is dependent on the model drug solubility. The AmB-loaded nanoparticles
      displayed no toxicity in tissue culture in contrast to free drug and were almost
      as efficacious as free drug in killing Candida albicans. Advantages of this
      simple technique are (1) ease of manufacturing and mild preparation conditions,
      (2) employment of completely aqueous processing conditions, (3) use of
      biocompatible polymers that can be prepared aseptically, (4) ability to control
      their size, and (5) a high level of drug entrapment.

PMID- 11458339
TI  - Iontophoretic transport of oligonucleotides across human epidermal membrane: a
      study of the Nernst-Planck model.
AB  - The objective of this study was to investigate the transport behavior of a series
      of oligonucleotides with human epidermal membrane (HEM) and to examine the
      applicability of the modified NERNST-PLANCK model to transdermal iontophoresis of
      these macromolecules. Iontophoretic transport experiments were first carried out
      in a synthetic model membrane system (Nuclepore membranes) with a four-electrode
      potentiostat to examine the baseline modified NERNST-PLANCK model. The modified
      NERNST-PLANCK model derived from the Einstein relation and the Stokes-Einstein
      equation taken from previous work did not hold for the oligonucleotides. Results
      obtained in the Nuclepore studies were, however, consistent with predictions of
      the modified NERNST-PLANCK model using the experimentally determined
      electromobilities and diffusion coefficients. The electromobilities of the
      oligonucleotides (determined by capillary electrophoresis) were found to be more
      than a factor of two smaller than expected from the Einstein relation between
      electromobilities and diffusion coefficients (the latter determined in diffusion
      cell experiments). A correlation between these electromobilities and the
      theoretical electromobilities estimated by considering the effects of counterion
      binding and the effects of mobility reduction according to colloid theory was
      also observed. These results suggest that the modified NERNST-PLANCK model
      predictions are satisfactory only when the electromobilities and the effective
      molecular size of the oligonucleotides are known and are used directly to predict
      the iontophoretically enhanced transport. Results with the HEM experiments
      generally agreed with model predictions based on the experimental
      electromobilities. The oligonucleotide HEM flux data also suggest the existence
      of pores with effective pore radii greater than the effective radii estimated in
      previous studies with small molecular weight model permeants.

PMID- 11458340
TI  - Quantification of pore induction in human epidermal membrane during
      iontophoresis: the importance of background electrolyte selection.
AB  - It has been shown that significant pore induction (electroporation) occurs in
      human epidermal membrane (HEM) during iontophoresis even at moderate applied
      voltages (1-10 V). Recent efforts in our laboratory have been aimed at
      quantifying HEM electroporation by examining the proportionality between flux
      enhancement due to electroporation and electrical conductance changes during
      iontophoresis. The specific purpose of the present study was to test the
      hypothesis that by matching the background electrolyte ion sizes with the
      permeant ion sizes, the flux enhancement due to electroporation can be quantified
      by the change in HEM electrical conductance. In this study, radiolabeled
      tetraethylammonium (TEA(+)), methylammonium (MA(+)), and mannitol were the
      permeants. Potassium chloride (KCl), tetraethylammonium bromide (TEAB),
      tetraethylammonium pivalate (TEAP), and sodium fluoride (NaF) were the background
      electrolytes. Iontophoresis experiments were carried out over an applied voltage
      range of 1 to 3 V. The experimental flux enhancement results were compared with
      the theoretical predictions from the Nernst-Planck model after corrections were
      made: (a) for HEM pore induction during iontophoresis based on electrical
      conductance changes and (b) for electroosmosis employing mannitol as the neutral
      probe permeant. In experiments where the ion sizes of the background electrolyte
      and permeant were closely matched (e.g., TEA(+) as the permeant and TEAP as the
      background electrolyte), there was excellent agreement between experimental
      results and theoretical predictions of the modified Nernst-Planck model, with
      only modest data scatter. When the electrolyte and permeant sizes were quite
      different (e.g., TEA(+)/KCl and MA(+)/TEAP), the experimental flux data were
      inconsistent with model predictions and there were large variations in the
      experimental results. The results of the present study illustrate that permeant
      flux enhancement can be predicted by the modified Nernst-Planck model even during
      moderate voltage iontophoresis when electroporation is operative.

PMID- 11458341
TI  - A stable gas chromatography-mass spectrometry analysis system to characterize Ma
      Huang products found in health foods and supplements.
AB  - Herbal mixtures containing Ma Huang are of significant interest because of their
      popularity regardless of their potential health hazards. In spite of reports of
      health problems and even several deaths, these products are still frequently
      recommended for use. The complex nature of the commercial supplement mixtures has
      posed a problem in both their qualitative and quantitative analysis. A gas
      chromatographic procedure has been developed to evaluate authenticity of Ma Huang
      mixtures. Mass spectrometric identification of the six major alkaloid ephedrine
      components and application of chi-square evaluation of the chromatographic
      profile allows a determination to be made regarding the nature of the origin of
      the mixture. For comparison, a standard mixture was prepared that approximates a
      typical Ma Huang composition based on average amounts of each alkaloid component
      reported in the literature. The system is temperature stable and allows
      simultaneous analysis for caffeine and other components of the commercial
      supplements. Several samples of commercial herbal products were analyzed by the
      procedure, and their composition is evaluated and discussed.

PMID- 11458342
TI  - Polymorphism of racemic felodipine and the unusual series of solid solutions in
      the binary system of its enantiomers.
AB  - The aim of this study was to investigate the binary phase diagram and the
      polymorphism and pseudopolymorphism of racemic and enantiomeric felodipine,
      including their spectroscopic and thermodynamic properties. Different crystal
      forms were obtained by crystallization from solvents or from the annealed melt
      and investigated by thermal analysis (hot stage microscopy, differential scanning
      calorimetry, thermogravimetric analysis), spectroscopic methods (Fourier
      transform infrared-and Fourier transform-Raman spectroscopy), and X-ray powder
      diffractometry. The binary melting phase diagram was constructed based on
      thermoanalytical investigations of quantitative mixtures of (+)- and (+/-)
      felodipine. Two polymorphic forms of racemic felodipine, mod. I (mp,
      approximately 145 degrees C) and mod. II (mp, approximately 135 degrees C), as
      well as an acetone solvate (S(Ac )) were characterized. Melting equilibria of
      felodipine crystal forms decrease due to thermal decomposition. Enantiomeric
      felodipine was found to be dimorphic (En-mod. I: mp, approximately 144 degrees C;
      En-mod. II: mp, approximately 133 degrees C). Evaluation of the binary system of
      (+)- and (-)-felodipine results in the formation of a continuous series of mixed
      crystals between the thermodynamically stable and higher melting modifications,
      mod. I and En-mod. I. Their unusual curve course, termed as Roozeboom Type 2 b,
      passes through a maximum in the racemic mixture and is flanked by a minimum at
      20% and at 80% (+)-felodipine. From the thermodynamic parameters, racemic mod. I
      and II are monotropically related. In contrast to S(Ac), the thermodynamically
      unstable mod. II shows a considerable kinetic stability. Because its
      crystallization is badly reproducible, the use of mod. II is not advisable for
      processing. However, desolvation of S(Ac) leads to a profitable crystal shape of
      mod. I, representing a pseudoracemate by definition.

PMID- 11458343
TI  - Biased estimates of nonrenal clearance.
AB  - The goal of the investigation was to critically evaluate published values for
      oral nonrenal clearance and their postulated dependence on renal function with
      drugs administered orally to subjects with varying renal function. Derivation of
      the pertinent equations indicated that the values reported for oral nonrenal
      clearance tend to systematically overestimate both the true oral and intravenous
      nonrenal clearances of these drugs. Computations were performed to confirm these
      findings not only for subjects with normal renal function, but also for patients
      with renal impairment. The computations evaluated the relevance of
      bioavailability and renal clearance of a drug for the bias in the estimates of
      true oral or intravenous nonrenal clearance. The results of the computations
      showed that the estimates for true oral and intravenous nonrenal clearance
      derived from oral data exceed systematically the true values in subjects with
      normal or reduced renal function. Also, a renal function dependent decrease of
      the true oral or intravenous nonrenal clearance is falsely diagnosed if apparent
      oral nonrenal clearance values are used for the estimates. The magnitude of
      bioavailability and renal clearance impact the bias in the estimates derived from
      oral data. For drugs with predominant renal excretion and small bioavailability
      the bias is largest. For drugs with predominant nonrenal elimination and large
      bioavailability the bias is smallest.

PMID- 11458346
TI  - The Discovery of Polyacetylene Film: The Dawning of an Era of Conducting Polymers
      (Nobel Lecture) Copyright((c)) The Nobel Foundation 2001. We thank the Nobel
      Foundation, Stockholm, for permission to print this lecture. 
AB  - This lecture is not directly related to our discovery and development of
      conducting polymers to which the Nobel Prize in Chemistry 2000 was awarded.
      However, I would like to present my previous work that I had carried out just
      before we reached the discovery of chemical doping. I hope that this will be of
      use and deepen your understandings by learning what had happened before and how
      we reached the idea of chemical doping.

PMID- 11458347
TI  - "Synthetic Metals": A Novel Role for Organic Polymers (Nobel Lecture)
      Copyright((c)) The Nobel Foundation 2001. We thank the Nobel Foundation,
      Stockholm, for permission to print this lecture. 
AB  - Since the initial discovery in 1977, that polyacetylene (CH)(x), now commonly
      known as the prototype conducting polymer, could be p- or n-doped either
      chemically or electrochemically to the metallic state, the development of the
      field of conducting polymers has continued to accelerate at an unexpectedly rapid
      rate and a variety of other conducting polymers and their derivatives have been
      discovered. Other types of doping are also possible, such as "photo-doping" and
      "charge-injection doping" in which no counter dopant ion is involved. One
      exciting challenge is the development of low-cost disposable plastic/paper
      electronic devices. Conventional inorganic conductors, such as metals, and
      semiconductors, such as silicon, commonly require multiple etching and
      lithographic steps in fabricating them for use in electronic devices. The number
      of processing and etching steps involved limits the minimum price. On the other
      hand, conducting polymers combine many advantages of plastics, for example,
      flexibility and processing from solution, with the additional advantage of
      conductivity in the metallic or semiconducting regimes; however, the lack of
      simple methods to obtain inexpensive conductive polymer shapes/patterns limit
      many applications. Herein is described a novel, simple, and cheap method to
      prepare patterns of conducting polymers by a process which we term, "Line
      Patterning".

PMID- 11458348
TI  - Semiconducting and Metallic Polymers: The Fourth Generation of Polymeric
      Materials (Nobel Lecture) Copyright(c) The Nobel Foundation 2001. We thank the
      Nobel Foundation, Stockholm, for permission to print this lecture. 
AB  - When asked to explain the importance of the discovery of conducting polymers, I
      offer two basic answers: first they did not (could not?) exist, and second, that
      they offer a unique combination of properties not available from any other known
      materials. The first expresses an intellectual challenge; the second expresses a
      promise for utility in a wide variety of applications.

PMID- 11458349
TI  - The Reaction Mechanism of the Enzyme-Catalyzed Central Cleavage of beta-Carotene
      to Retinal This research was supported by F. Hoffmann-La Roche AG and the Swiss
      National Science Foundation. We are grateful to F. Hoffmann-La Roche AG for a
      generous gift of carotenoids and Dr. Claus Bornemann for preliminary experiments.

PMID- 11458350
TI  - Saddle-Shaped Six-Coordinate Iron(III) Porphyrin Complexes Showing a Novel Spin
      Crossover between S=1/2 and S=3/2 Spin States This work was supported by a Grant
      in Aid for Scientific Research on Priority Areas (A; no. 12020257 to M.N.) from
      the Ministry of Education, Culture, Sports, Science, and Technology, Japan. T.I.
      is grateful to the JSPS for a Research Fellowship for young scientists. We thank
      the Research Center for Molecular Materials, the Institute for Molecular Science
      (IMS), for support. The authors are grateful to Mr. Masahiro Sakai of the IMS for
      the assistance with the SQUID measurements. 

PMID- 11458351
TI  - Molecular Paneling by Coordination: An M(15)L(6) Hexahedral Molecular Capsule
      having Clefts for Reversible Guest Inclusion.

PMID- 11458352
TI  - A Chiral Metal Surface We would like to acknowledge fruitful discussions with
      Trolle Linderoth as well as the financial support from the Danish National
      Research Foundation through the Center for Atomic-scale Materials Physics (CAMP),
      from the VELUX Foundation, and from the EU networks "Manipulation of individual
      atoms and molecules" and "Bottom up Nanomachines". 

PMID- 11458353
TI  - Organophosphorus Dendrimers as New Gelators for Hydrogels.

PMID- 11458354
TI  - trans-

PMID- 11458355
TI  - Synthesis, Biological, and Immunological Properties of Cyclic Peptides from
      Plasmodium Falciparum Merozoite Surface Protein-1 This work was supported by a
      long-term fellowship of the Human Frontier Science Program Organization (HFSPO-LT
      25/97) and by a Research Grant from the Roche Research Foundation. 

PMID- 11458356
TI  - Zeosil Nanoslabs: Building Blocks in nPr(4)N(+)-Mediated Synthesis of MFI Zeolite
      C.E.A.K., J.A.M., and P.A.J. acknowledge the Belgian Government for sponsoring in
      the frame of IUAP-PAI program. J.A.M. and P.A.J. acknowledge FWO Vlaanderen for a
      research grant. 

PMID- 11458357
TI  - A Colorimetric ATP Sensor Based on 1,3,5-Triarylpent-2-en-1,5-diones This
      research was supported by the Ministerio de Ciencia y Tecnologia (proyecto PB98
      1430-C02-02, 1FD97-0508-C03-01, and AMB99-0504-C02-01). F.S. also thanks the
      Ministerio de Educacion y Cultura for a Doctoral Fellowship. 

PMID- 11458358
TI  - High-Pressure Synthesis of gamma-P(3)N(5) at 11 GPa and 1500 degrees C in a
      Multianvil Assembly: A Binary Phosphorus(V) Nitride with a Three-Dimensional
      Network Structure from PN(4) Tetrahedra and Tetragonal PN(5) Pyramids This work
      was supported by the Fonds der Chemischen Industrie and the Deutsche
      Forschungsgemeinschaft (Gottfried-Wilhelm-Leibniz-Programm). The authors thank
      Dr. D. Frost and Prof. Dr. D. C. Rubie, Bayerisches Geoinstitut, Universitat
      Bayreuth, as well as Dr. P. Ulmer, ETH Zurich, for help in adapting the
      multianvil-technique. Also many thanks to W. Wunschheim, Department Chemie, LMU
      Munchen for the development and programming of software for the high-pressure
      experiments. 

PMID- 11458359
TI  - Physically Cross-Linked Ultrathin Elastomeric Membranes This work was supported
      by the Max-Planck Gesellschaft, the Deutsche Forschungsgemeinschaft (project Go
      693/2), and the Kalhof-Rose Stiftung. The experiments were conducted at the Max
      Planck-Institut fur Kolloid- & Grenzflachenforschung, Berlin. We thank H. Mohwald
      (MPI-KGF), M. Antonietti (MPI-KGF), M. Moller (Universitat Ulm), and J. Rabe
      (Humboldt Universitat Berlin) for support and fruitful discussions. 

PMID- 11458360
TI  - A Cyclic Hexapeptide Containing L-Proline and 6-Aminopicolinic Acid Subunits
      Binds Anions in Water This work was sponsored by the Deutsche
      Forschungsgemeinschaft. S.K. thanks D. Kubik for her committed help with the
      synthetic work and Prof. G. Wulff for his support. 

PMID- 11458361
TI  - First O-H-N Hydrogen Bond with a Centered Proton Obtained by Thermally Induced
      Proton Migration Parts of this work were supported through EPSRC grant GR/L7102
      (to C.C.W.).

PMID- 11458362
TI  - Nitroglycal Concatenation: A Broadly Applicable and Efficient Approach to the
      Synthesis of Complex O-Glycans This work was supported by the Deutsche
      Forschungsgemeinschaft and the European Community (grant no. FAIR-CT 97-3142).
      G.A.W. gratefully acknowledges a RIKEN/Studienstiftung des Deutschen Volkes
      fellowship. We are grateful to Dr. A. Geyer for his help in the structural
      assignments by NMR experiments and to Dr. K.-H. Jung for his help in the
      preparation of the manuscript. 

PMID- 11458363
TI  - Barium Triphenylmethanide: An Examination of Anion Basicity This work was
      supported by the National Science Foundation (CHE-9702246). Purchase of the X-ray
      Diffractometer was made possible with grants from the NSF (CHE-95-27898), the W.
      M. Keck Foundation, and Syracuse University. 

PMID- 11458364
TI  - Dicyclopenta

PMID- 11458365
TI  - Nonorthogonal Dilithium-1,3-biborataallenes Containing Planar-Tetracoordinate
      Carbon Atoms This work was supported by Deutsche Forschungsgemeinschaft and the
      Fonds der Chemischen Industrie. 

PMID- 11458366
TI  - Synthesis and Structure of a Dimeric Alkyldibariumtriszincate with a Tetraanionic
      Triszincate Ligand and a Unique Central Ba(4)Zn(2)C(6) Moiety This research was
      supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
      Industrie. We are also grateful to Prof. Dr. P. Klufers and Dr. H. Piotrowski for
      their kind assistance. 

PMID- 11458367
TI  - Synthesis of a Nanoporous Polymer with Hexagonal Channels from Supramolecular
      Discotic Liquid Crystals We gratefully acknowledge the Korean Ministry of Science
      and Technology (Creative Research Initiative Program) for support of this work,
      and the Korean Ministry of Education (Brain Korea 21 program) for graduate
      studentships (H.-K.L. and Y.J.C). We also thank Dr. Y. S. Kang and Mr. J. H. Kim
      for gas permeability experiments and Prof. B. H. Sohn and Prof. P. K. Bharadwaj
      for helpful discussions. The X-ray diffraction measurements were performed at the
      Pohang Accelerator Laboratory (Beamline 3C2). 

PMID- 11458368
TI  - Enantioselective Incorporation of Azobenzenes into Oligodeoxyribonucleotide for
      Effective Photoregulation of Duplex Formation This work was partially supported
      by a Grant-in-Aid for Scientific Research from the Ministry of Education,
      Culture, Sports, Science and Technology, Japan (Molecular Synchronization for
      Design of New Materials System). The support by the Grant from "Research for the
      Future" Program of the Japan Society for the Promotion of Science (JSPS
      RFTF97I00301) is also acknowledged. 

PMID- 11458369
TI  - Cleavage of Tellurium-Carbon Bonds of Hexavalent Organotellurium Compounds by
      Potassium Graphite This work was supported by a Grant-in-Aid for Scientific
      Research (No. 11304044 and 12740352) from the Ministry of Education, Science,
      Sports, and Culture of the Japanese Government. The support of the Nishida
      Research Fund for Fundamental Organic Chemistry (to M. Minoura) is also
      acknowledged. 

PMID- 11458370
TI  - Highly Sensitive Novel Biosensor Based on an Immobilized lac Repressor This work
      was supported with grants given by the Swedish Engineering Research Council
      (TFR). Prof. Muller Hill and Dr. Andrew Barker are acknowledged for providing
      plasmids and the Escherichia coli BMH 8117 strain. 

PMID- 11458371
TI  - Noncovalent Assembly of

PMID- 11458372
TI  - Synthetic seco Forms of (-)-Diazonamide A We thank Prof. Michael Roth for advice
      and insight and Ms. Susan Jeong for invaluable experimental assistance. Funding
      was provided by the NIH (RO1-GM60591), the NSF (CAREER 9984282), the Howard
      Hughes Medical Institute (junior faculty support), and the Robert A. Welch
      Foundation. 

PMID- 11458373
TI  - Ring-Opening Polymerization of 1-Methylene-2-phenylcyclopropane Catalyzed by a Pd
      Complex To Afford Regioregulated Polymers This work was supported by a Grant-in
      Aid for Scientific Research from the Ministry of Education, Science, Sports, and
      Culture, Japan. 

PMID- 11458374
TI  - Nematic Dendrimers Based on Carbosilazane Cores We acknowledge the EU for funding
      in the framework of the TMR network "Molecular Design of Functional Liquid
      Crystals" and thank the members of the network for the many helpful discussions. 

PMID- 11458375
TI  - Spin-Labeled Dendrimers in EPR Imaging with Low Molecular Weight Nitroxides.

PMID- 11458376
TI  - Photochemical Carbonylation of Ethane under Supercritical Conditions This work is
      supported by the Research Corporation and the Director, Office of Science, Office
      of Basic Energy Sciences, Chemical Sciences Division of the US Department of
      Energy under contract DE-ACO6-76RLO 1830. 

PMID- 11458377
TI  - Rearrangement of a Tricyclic 2,5-Cyclohexadienone: Towards a General Synthetic
      Route to the Daphnanes and (+)-Resiniferatoxin We wish to gratefully acknowledge
      the support of Daiso Ltd., Japan (M.M.), and Meiji Seika Kaisha Ltd., Japan
      (S.S.). M.J. thanks Pharmacia-UpJohn for a graduate fellowship during his third
      year at Caltech. Financial support was provided by the Packard Foundation, the
      National Science Foundation (USA), the National Institutes of Health (USA), and
      by generous funds from Eli Lilly, Merck, Novartis, Pfizer, Pharmacia-Upjohn,
      Zeneca, the Eidgenossische Technische Hochschule (ETH), the Kontaktgruppe fur
      Forschungsfragen (KGF), and Hoffmann La Roche. 

PMID- 11458378
TI  - Activation, Tuning, and Immobilization of Homogeneous Catalysts in an Ionic
      Liquid/Compressed CO(2) Continuous-Flow System This work was supported by the Max
      Planck Society, the DFG (Gerhard-Hess-Award to W.L.), and the Fonds der
      Chemischen Industrie. The fruitful input of Dipl.-Chem. Heike Stemmer and Dr.
      Andreas Wegner (both Mulheim) during the early phase of the project is gratefully
      acknowledged. 

PMID- 11458380
TI  - Remote Communication between Charge Centers and Hydrogen-Bonding Sites:
      Possibility for a Signal Transducer? This work was supported by the National
      Science Council and Academia Sinica of Taiwan (ROC). The granting of computer
      time by the National Center for High-Performance Computing and the Computing
      Center of Academia Sinica is acknowledged. We also thank Ning Juan for her
      assistance in preparing the manuscript. 

PMID- 11458379
TI  - Polymetallic Cobalt and Manganese Cages with Phosphinate and Phosphonate Ligands
      This work was supported by the EPSRC (UK). 

PMID- 11458381
TI  - nido<-->closo Interconversion of Six-Vertex Metallacarboranes: Access to
      CoC(2)B(3) and CoC(2)B(4) Clusters with Nonadjacent Carbon Atoms Organotransition
      Metal Metallacarboranes, part 57. This work was supported in part by the National
      Science Foundation (grant CHE 9980708) and the Alexander von Humboldt Foundation
      (Feodor Lynen postdoctoral fellowship to H.-J. Schanz). Part 56: M. Bluhm, H.
      Pritzkow, W. Siebert, R. N. Grimes, Angew. Chem. 2000, 112, 4736; Angew. Chem.
      Int. Ed. 2000, 39, 4562. 

PMID- 11458382
TI  - Inherent Asymmetry of Constitutionally Equivalent Methyl Groups in the H/D
      Equilibration of n- and i-C(3)H(7)Fe(OH)(+) Complexes We thank the Volkswagen
      Stiftung, the Deutsche Forschungsgemeinschaft, and the Fonds der Chemischen
      Industrie for generous funding. 

PMID- 11458383
TI  - A Novel Hemiporphyrazine Comprising Three Isoindolediimine and Three Thiadiazole
      Units This work was supported partly by a Grant-in-Aid for Scientific Research
      (B) No. 11440192 and the Shorai Foundation for Science & Technology. 

PMID- 11458385
TI  - Combinatorial Chemistry in the Commercial Jungle.

PMID- 11458384
TI  - New Paradigms for Organic Catalysts: The First Organocatalytic Living
      Polymerization The authors would like to thank the NSF Center on Polymer
      Interfaces and Macromolecular Assemblies (CPIMA). T.G. expresses his thanks to
      the Swiss Academy of Engineering Sciences (SATW) and the Swiss National Science
      Foundation. 

PMID- 11458386
TI  - Sodium-calcium exchanger (NCX-1) and calcium modulation: NCX protein expression
      patterns and regulation of early heart development.
AB  - Ouabain-induced inhibition of early heart development indicated that Na/K-ATPase
      plays an important role in maintaining normal ionic balances during
      differentiation of cardiomyocytes (Linask and Gui [1995] Dev Dyn 203:93-105).
      Inhibition of the sodium pump is generally accepted to affect the activity of the
      Na(+)-Ca(++) exchanger (NCX) to increase intracellular [Ca(++)]. These previous
      findings suggested that Ca(++) signaling may be an important modulator during
      differentiation of cardiomyocytes. In order to identify a connection between
      heart development and NCX-mediated Ca(++) regulation, we determined the embryonic
      spatiotemporal protein expression pattern of NCX-1 during early developmental
      stages. In both chick and mouse embryos, NCX-1 (the cardiac NCX isoform) is
      asymmetrically expressed during gastrulation; in the right side of the Hensen's
      node in the chick, in the right lateral mesoderm in the mouse. At slightly later
      stages, NCX-1 is expressed in the heart fields at comparable stages of heart
      development, in the chick at stage 7 and in the mouse at embryonic day (ED) 7.5.
      By ED 8 in the mouse, the exchanger protein displays a rostrocaudal difference in
      cardiac expression and an outer curvature-inner curvature ventricular difference.
      By ED 9.5, cardiac expression has increased from that seen at ED8 and NCX-1 is
      distributed throughout the myocardium consistent with the possibility that it is
      important in regulating initial cardiac contractile function. Only a low level of
      expression is detected in inflow and outflow regions. To substantiate a role for
      the involvement of calcium-mediated signaling, using pharmacologic approaches,
      ionomycin (a Ca(++) ionophore) was shown to perturb cardiac cell differentiation
      in a manner similar to ouabain as assayed by cNkx2.5 and sarcomeric myosin heavy
      chain expression. In addition, we show that an inhibitor of NCX, KB-R7943, can
      similarly and adversely affect early cardiac development at stage 4/5 and arrests
      cardiac cell contractility in 12-somite embryos. Thus, based upon NCX-1 protein
      expression patterns in the embryo, experimental Ca(++) modulation, and inhibition
      of NCX activity by KB-R7943, these results suggest an early and central role for
      calcium-mediated signaling in cardiac cell differentiation and NCX's regulation
      of the initial heartbeats in the embryo.

PMID- 11458387
TI  - Multiple growth factors regulate coronary embryonic vasculogenesis.
AB  - Mechanisms regulating coronary vascularization are not well understood. To test
      hypotheses regarding the influence of key growth factors and their interactions,
      we studied vascular tube formation (vasculogenesis) in collagen gels onto which
      quail embryonic ventricles were placed and incubated in the presence of growth
      factors or inhibitors. Vasculogenesis in this model is dependent on tyrosine
      kinase receptors, since tube formation was totally blocked by genestein. Tube
      formation was attenuated when anti-bFGF or anti-VEGF neutralizing antibodies were
      added to the medium and nearly completely inhibited when the both were added. The
      attenuation associated with anti-VEGF was due primarily to a decrease in assembly
      of endothelial cells, while that associated with bFGF was primarily due to a
      reduction in endothelial cells. Soluble tie-2, the receptor for angiopoietins,
      also had an inhibitory effect and, when added with either anti-bFGF or anti-VEGF,
      markedly attenuated tube formation. At optimal doses, tube formation was enhanced
      6.5-fold by bFGF and 2.5-fold by VEGF over the controls. Each of these growth
      factors was dependent upon the other for optimal induction of tube formation,
      since neutralizing antibodies to one markedly reduced the potency of the other.
      VEGF potency was also markedly reduced when soluble tie-2 was added to the
      medium. Tube formation was virtually totally blocked by exogenous TGF-beta at
      doses > 1 ng/ml, while neutralizing TGF-beta antibodies enhanced tube formation 2
      fold in the 30 ng-30 microg range. These data provide the first documentation of
      multiple growth factor regulation of coronary tube formation.

PMID- 11458388
TI  - Two upstream enhancers collaborate to regulate the spatial patterning and timing
      of MyoD transcription during mouse development.
AB  - MyoD is a member of the basic-helix-loop-helix (bHLH) transcription factor
      family, which regulates muscle determination and differentiation in vertebrates.
      While it is now well established that the MyoD gene is regulated by Sonic
      hedgehog, Wnts, and other signals, it is not known how MyoD transcription is
      initiated and maintained in response to these signals. We have investigated the
      cis control of MyoD expression to identify and characterize the DNA targets that
      mediate MyoD transcription in embryos. By monitoring lacZ reporter gene
      expression in transgenic mice, we show that regulatory information contained in
      24 kb of human MyoD 5' flanking sequence is sufficient to accurately control MyoD
      expression in embryos. Previous studies have identified two muscle-specific
      regulatory regions upstream of MyoD, a 4-kb region centered at -20 kb (designated
      fragment 3) that contains a highly conserved 258-bp core enhancer sequence, and a
      more proximal enhancer at -5 kb, termed the distal regulatory region (DRR), that
      heretofore has been identified only in mice. Here, we identify DRR-related
      sequences in humans and show that DRR function is conserved in humans and mice.
      In addition, transcriptional activity of MyoD 5' flanking sequences in somites
      and limb buds is largely a composite of the individual specificities of the two
      enhancers. Deletion of fragment 3 resulted in dramatic but temporary expression
      defects in the hypaxial myotome and limb buds, suggesting that this regulatory
      region is essential for proper temporal and spatial patterning of MyoD
      expression. These data indicate that regulatory sequences in fragment 3 are
      important targets of embryonic signaling required for the initiation of MyoD
      expression.

PMID- 11458389
TI  - TGF-beta1 perturbs vascular development and inhibits epithelial differentiation
      in fetal lung in vivo.
AB  - Members of the transforming growth factor beta (TGF-beta) family of polypeptides
      have been implicated in morphogenesis and differentiation in numerous tissues,
      including the lung. In order to further define effects of TGF-beta signaling in
      lung morphogenesis, a constitutively active form of TGF-beta1 was expressed in
      respiratory epithelial cells of the fetal mouse lung in vivo. Expression of TGF
      beta1 arrested lung morphogenesis in the pseudoglandular stage of development,
      inhibiting synthesis of differentiation-dependent proteins, SP-B, SP-C, and CCSP,
      and maintaining embryonic patterns of staining for thyroid transcription factor-1
      (TTF-1) and hepatocyte nuclear factor-3beta (HNF-3beta). The pulmonary mesenchyme
      was thickened and vascular density was increased by TGF-beta1. TGF-beta1
      decreased expression of vascular endothelial growth factor-A (VEGF-A) mRNA and
      protein, and the abundance of Flk-1 mRNA in the lung mesenchyme. Distribution of
      platelet-endothelial cell adhesion molecule (PECAM)-1, a marker of pulmonary
      blood vessels, was altered, and ultrastructural studies demonstrated that TGF
      beta1 inhibited vascular development in the fetal lung. TGF-beta1 perturbed both
      epithelial cell differentiation and formation of the pulmonary vasculature,
      supporting the concept that precise control of signaling via the TGF-beta
      receptor pathway is critical for normal lung morphogenesis.

PMID- 11458390
TI  - Apoptosis and proliferation in the neonatal murine heart.
AB  - The spatial and temporal patterns of apoptosis and proliferation in timed fetal,
      neonatal, and adult murine hearts have been determined using an in situ end
      labeling technique for detecting fragmented DNA, and bromodeoxyuridine
      immunofluorescence as a marker for DNA synthesis. Also, cardiac expression of
      apoptosis-related proteins was assessed by immunofluorescence. Prominent
      apoptotic labeling was found in the right ventricular subendocardium and the
      basal septum in the area of the developing conduction system. In the right
      ventricle, apoptotic labeling surged late in the first day postpartum, then
      declined to levels similar to the left ventricle by postpartum day 8.5. Apoptotic
      labeling at the basal septum was greatest peripartum and gradually declined to
      levels seen in the rest of the heart by postpartum day 8.5. Cessation of
      proliferation did not occur simultaneously throughout the neonatal heart. Through
      postpartum day 4.5, incorporation of BrdU was greater in the left ventricle than
      in the right ventricle, particularly in the subendocardium. Bax and Fas,
      proapoptotic proteins, were detected homogeneously throughout both ventricles in
      the neonate, while Bcl-2, an antiapoptotic protein, was not detectable. These
      data suggest that postnatal cardiac remodeling results from changes in both
      apoptosis and proliferation. Furthermore, the temporal and spatial pattern of
      these processes, coincident with the hemodynamic changes associated with
      parturition, suggests that both processes may be regulated by mechanical factors.

PMID- 11458391
TI  - The perichondrium plays an important role in mediating the effects of TGF-beta1
      on endochondral bone formation.
AB  - Endochondral bone formation is complex and requires the coordination of signals
      from several factors and multiple cell types. Thus, chondrocyte differentiation
      is regulated by factors synthesized by both chondrocytes and cells in the
      perichondrium. Previously, we showed that expression of a dominant-negative form
      of the transforming growth factor beta (TGF-beta) type II receptor in
      perichondrium/periosteum resulted in increased hypertrophic differentiation in
      growth plate chondrocytes, suggesting a role for TGF-beta signaling to the
      perichondrium in limiting terminal differentiation in vivo. Using an organ
      culture model, we later demonstrated that TGF-beta1 inhibits chondrocyte
      proliferation and hypertrophic differentiation by two separate mechanisms.
      Inhibition of hypertrophic differentiation was shown to be dependent on
      Parathyroid hormone-related peptide (PTHrP) and expression of PTHrP mRNA was
      stimulated in the perichondrium after treatment with TGF-beta1. In this report,
      the hypothesis that the perichondrium is required for the effects of TGF-beta1 on
      growth and/or hypertrophic differentiation in mouse metatarsal organ cultures is
      tested. Treatment with TGF-beta1 inhibited expression of type X collagen mRNA in
      metatarsal cultures with the perichondrium intact. In contrast, hypertrophic
      differentiation as measured by expression of Type X collagen was not inhibited by
      TGF-beta1 in perichondrium-free cultures. TGF-beta1 added to intact cultures
      inhibited BrdU incorporation in chondrocytes and increased incorporation in the
      perichondrium; however, TGF-beta1 treatment stimulated chondrocyte proliferation
      in metatarsals from which the perichondrium had been enzymatically removed. These
      results suggest that the TGF-beta1-mediated regulation of both chondrocyte
      proliferation and hypertrophic differentiation is dependent upon the
      perichondrium. Thus, one or several factors from the perichondrium might mediate
      the way chondrocytes respond to TGF-beta1.

PMID- 11458392
TI  - Characterization and mutant analysis of the Drosophila sema 5c gene.
AB  - Class V semaphorins are transmembrane glycoproteins characterised by the presence
      of thrombospondin type I (Tsp) repeats linked to their extracellular semaphorin
      domain. Sema 5C is the only class V semaphorin found in Drosophila. Dsema 5C RNA
      is maternally provided and its embryonic expression is prominent in the mesoderm
      and muscle attachment sites. Here, we show that DSema 5C exists in two protein
      isoforms as a result of alternative splicing and that both protein and RNA have
      similar expression patterns. Using a combination of various molecular markers, we
      show that the DSema 5C protein becomes enriched in mesodermal cells that would
      normally give rise to fat body and visceral structures. In late embryos, DSema 5C
      is expressed in segment boundary cells that would constitute subsets of muscle
      attachment sites. Both RNA and protein are excluded from the somatic precursors
      and the mature muscles. The expression data suggest DSema 5C localised to the
      epidermal component of muscle attachment sites. Mutations in Dsema 5C were
      isolated from a P-element excision screen and by blotting analysis. The Dsema 5C
      mutants are homozygous viable and show no obvious embryonic phenotypes,
      suggesting that the maternal and zygotic components of Dsema 5C are not essential
      for fly development.

PMID- 11458393
TI  - Sequential expression of three receptor subtypes for extracellular ATP in
      developing rat skeletal muscle.
AB  - In this study, we investigated the expression of the P2X receptor subtypes (P2X(1
      7)) during the development of skeletal muscle and in relation to acetylcholine
      receptors in the rat embryo and pup. By using immunohistochemistry, we showed
      that three receptor subtypes, P2X(2), P2X(5), and P2X(6), were expressed in
      developing skeletal muscle. The timing and pattern of receptor expression seemed
      to be precisely regulated. P2X(2), P2X(5), and P2X(6) were expressed in a
      sequential manner, which was consistent for all regional muscles tested
      (intercostal, paravertebral, and lower limb): P2X(5) expression appeared first
      (E15-E18) followed by P2X(6) (E16-E18), and finally P2X(2) (E18-adult). At no
      developmental stage did we observe colocalization of P2X(2) and acetylcholine
      receptors. In the case of P2X(2) and P2X(6), immunoreactivity was found to be
      widespread, immunopositive cells being apparent throughout the muscle. However,
      staining for P2X(5), both at the beginning and end of expression, was restricted
      to regions of muscle close to the myotendinous junctions. Because the timing of
      receptor expression is closely related to key events in skeletal muscle
      development, notably the generation of secondary myotubes and the redistribution
      of acetylcholine receptors, it is possible that ATP-signaling by means of P2X
      receptors could be involved in these processes.

PMID- 11458394
TI  - Six3 promotes the formation of ectopic optic vesicle-like structures in mouse
      embryos.
AB  - A few years ago, three novel murine homeobox genes closely related to the
      Drosophila sine oculis (so) gene (Six1-3) were isolated and were all included in
      the Six/so gene family. Because of its early expression in the developing eye
      field, Six3 was initially thought to be the functional ortholog of the Drosophila
      so gene. This hypothesis was further supported by the demonstration that ectopic
      Six3 expression in medaka fish (Oryzias latipes) promotes the formation of
      ectopic lens and retina tissue. Here, we show that similar to Drosophila, where
      the eyeless/Pax6 gene regulates the eye-specific expression of so, Six3
      expression in the murine lens placodal ectoderm is also controlled by Pax6. We
      also show that ectopic Six3 expression promotes the formation of ectopic optic
      vesicle-like structures in the hindbrain-midbrain region of developing mouse
      embryos.

PMID- 11458395
TI  - Effects of retinoic acid upon eye field morphogenesis and differentiation.
AB  - This study describes a whole embryo and embryonic field analysis of retinoic
      acid's (RA) effects upon Xenopus laevis forebrain development and
      differentiation. By using in situ and immunohistochemical analysis of pax6, Xbf1,
      and tyrosine hydroxylase (TH), gene expression during eye field, telencephalon
      field, and retinal development was followed with and without RA treatment. These
      studies indicated that RA has strong effects upon embryonic eye and telencephalon
      field development with greater effects upon the ventral development of these
      organ fields. The specification and determination of separate eye primordia
      occurred at stage-16 when the prechordal plate reaches its most anterior aspect
      in Xenopus laevis. Differentiation of the dopaminergic cells within the retina
      was also affected in a distinct dorsoventral pattern by RA treatment, and cell
      type differentiation in the absence of distinct retinal laminae was also
      observed. It was concluded that early RA treatments affected organ field
      patterning by suppression of the upstream elements required for organ field
      development, and RA's effects upon cellular differentiation occur downstream to
      these organ determinants' expression within a distinct dorsoventral pattern.

PMID- 11458396
TI  - Neuropeptides in the amphibian brain: new insights.

PMID- 11458397
TI  - Vasotocin and mesotocin in the brains of amphibians: state of the art.
AB  - Immunohistochemical studies during the last decade have revealed elaborate
      systems of vasotocinergic (AVT) and mesotocinergic (MST) neuronal elements in the
      brain of a variety of amphibians including anurans, urodeles, and gymnophionans.
      Apart from a well-developed hypothalamo-hypophysial system, the antibodies
      demonstrated the existence of extrahypothalamic AVT- and MST-immunoreactive cell
      groups as well as extensive extrahypothalamic networks of immunoreactive fibers.
      The wide distribution of AVT- and MST-immunoreactive fibers throughout the brains
      of amphibians suggests that the two neuropeptidergic systems are involved not
      only in hypothalamo-hypophysial interactions, but also in a variety of other
      brain functions. Moreover, there is now evidence that sex-related differences
      occur in amphibians as previously shown for amniotes. It should be noted,
      however, that substantial variation occurs in the relative densities of AVT- and
      MST-immunoreactive fibers and number of cells between species, even within a
      single order of amphibians. Similar observations have been made in other classes
      of vertebrates and prompt us, therefore, to critically evaluate conclusions with
      respect to specific functions of AVT and MST in the central nervous system of
      vertebrates.

PMID- 11458398
TI  - Pituitary adenylate cyclase-activating polypeptide and its receptors in
      amphibians.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide of
      the secretin/glucagon/vasoactive intestinal polypeptide superfamily, has been
      initially characterized in mammals in 1989 and, only 2 years later, its
      counterpart has been isolated in amphibians. A number of studies conducted in the
      frog Rana ridibunda have demonstrated that PACAP is widely distributed in the
      central nervous system (particularly in the hypothalamus and the median eminence)
      and in peripheral organs including the adrenal gland. The cDNAs encoding the
      PACAP precursor and 3 types of PACAP receptors have been cloned in amphibians and
      their distribution has been determined by in situ hybridization histochemistry.
      Ontogenetic studies have revealed that PACAP is expressed early in the brain of
      tadpoles, soon after hatching. In the frog Rana ridibunda, PACAP exerts a large
      array of biological effects in the brain, pituitary, adrenal gland, and ovary,
      suggesting that, in amphibians as in mammals, PACAP may act as neurotrophic
      factor, a neurotransmitter and a neurohormone.

PMID- 11458399
TI  - FMRFamide in the amphibian brain: a comprehensive survey.
AB  - Mapping of FMRFamidergic neural circuitry in the amphibian brain has been done by
      immunohistochemical methods. Comparative evidence suggests that there are
      similarities and differences in the overall pattern of distribution of FMRFamide
      ir elements in the brain among the three amphibian orders and within each order.
      FMRFamide is expressed in neurons in some circumscribed areas of the brain. A
      part of these neurons is concentrated in classical neurosecretory areas of the
      hypothalamus in a bilaterally symmetrical fashion. Similar neurons occur
      occasionally in the midbrain, but are virtually absent from the hindbrain.
      Anurans are unique among amphibians to show FMRFamide neurons in the medial
      septum and diagonal band of Broca. A viviparous gymnophione is known to possess a
      small population of such neurons in the dorsal thalamus. Together, the FMRFamide
      neurons contribute to an extensive fiber network throughout the amphibian brain.
      Descriptive developmental studies suggest that the rostral forebrain-located
      FMRFamide neurons originate in the olfactory placode and then migrate into the
      brain along the route of the vomeronasal-olfactory-terminal nerve complex.
      Olfactory placodal ablation in an anuran and a urodele provide experimental
      support to this contention. Other FMRFamide neuronal cell groups, in the
      hypothalamus and dorsal thalamus, are supposed to arise from non-placodal
      precursors. The neuroanatomical distribution (projection of immunoreactive
      processes to areas of the fore-, mid-, and hindbrain as well as to cerebrospinal
      fluid, co-localization with other neuropeptides, and presence in the median
      eminence) has furnished morphological correlates of possible functions of
      FMRFamide in the amphibian CNS. While amphibian FMRFamide-like or structurally
      related peptides remain to be isolated and characterized, the sum of the
      distribution pattern of FMRFamide-like immunoreactivity suggests that it may act
      as a neurotransmitter or a neuromodulator, and also may have endocrine regulatory
      functions.

PMID- 11458400
TI  - Comparative analysis of adrenomedullin-like immunoreactivity in the hypothalamus
      of amphibians.
AB  - Adrenomedullin (AM) is a novel neuropeptide with special significance in the
      mammalian hypothalamo-hypophysial axis. By using an antiserum specific for human
      AM, we have studied the localization of AM-like immunoreactive (AMi) cell bodies
      and fibers in the hypothalamus and hypophysis of the amphibians Rana perezi
      (anuran), Pleurodeles waltl (urodele), and Dermophis mexicanus (gymnophionan).
      Distinct AMi cell groups were found for each species. In the anuran, six cell
      groups were localized in the preoptic and infundibular regions, whereas only
      three and one were found in the urodele and gymnophionan, respectively. A
      comparative analysis of AMi cells and cells expressing arginine vasotocin (AVT),
      neuropeptide Y (NPY), and tyrosine hydroxylase (TH) revealed strong differences
      between species. Thus, colocalization of AVT/AM is most likely to occur in the
      preoptic magnocellular nucleus of urodeles and it is reflected by the intense AM
      immunoreactivity in the neural lobe of the hypophysis. Colocalization of NPY/AM
      seems to be possible in the suprachiasmatic nucleus of anurans. In the
      gymnophionan, cells containing AVT and NPY are distinct from AMi cells. Only in
      anurans, the ventral aspect of the suprachiasmatic nucleus possesses a small
      population of AMi cells that express also TH immunoreactivity and most likely
      also express NPY. The results strongly suggest that AM in amphibians plays an
      important regulatory role in the hypothalamo-hypophysial system, as has been
      demonstrated in mammals. On the other hand, substantial differences have been
      found between species with respect to the degree of colocalization with other
      chemical substances.

PMID- 11458401
TI  - Dynamics and plasticity of peptidergic control centres in the retino-brain
      pituitary system of Xenopus laevis.
AB  - This review deals particularly with the recent literature on the structural and
      functional aspects of the retino-brain-pituitary system that controls the
      physiological process of background adaptation in the aquatic toad Xenopus
      laevis. Taking together the large amount of multidisciplinary data, a consistent
      picture emerges of a highly plastic system that efficiently responds to changes
      in the environmental light condition by releasing POMC-derived peptides, such as
      the peptide alpha-melanophore-stimulating hormone (alpha-MSH), into the
      circulation. This plasticity is exhibited by both the central nervous system and
      the pituitary pars intermedia, at the level of molecules, subcellular structures,
      synapses, and cells. Signal transduction in the pars intermedia of the pituitary
      gland of Xenopus laevis appears to be a complex event, involving various
      environmental factors (e.g., light and temperature) that act via distinct brain
      centres and neuronal messengers converging on the melanotrope cells. In the
      melanotropes, these messages are translated by specific receptors and second
      messenger systems, in particular via Ca(2+) oscillations, controlling main
      secretory events such as gene transcription, POMC-precursor translation and
      processing, posttranslational peptide modifications, and release of a bouquet of
      POMC-derived peptides. In conclusion, the Xenopus hypothalamo-hypophyseal system
      involved in background adaptation reveals how neuronal plasticity at the
      molecular, cellular and organismal levels, enable an organism to respond
      adequately to the continuously changing environmental factors demanding
      physiological adaptation.

PMID- 11458402
TI  - Common femoral artery anatomy is influenced by demographics and comorbidity:
      implications for cardiac and peripheral invasive studies.
AB  - We assessed the angiographic size of the common femoral artery (CFA) and the
      influence of demographics and comorbidites. In addition, the location of the CFA
      bifurcation and the site of femoral puncture were also assessed. Consecutive CFA
      angiograms (n = 200) were prospectively analyzed. CFA diameter was 6.9 +/- 1.4 mm
      and length 43.3 +/- 16.2 mm. By multivariate analysis, only diabetes (P < 0.001),
      female gender (P < 0.0005), and small body surface area (P < 0.01) predicted
      small vessel size. Vessel length correlated with patient height (P < 0.0005). CFA
      bifurcation occurred at or below the femoral head center in 98.5%. The femoral
      puncture was into a vessel other than the CFA in 13%, and 54% of punctures were
      in a less than ideal anatomical location. In conclusion, the CFA is a relatively
      small diameter vessel, particularly in diabetics and women. Puncture above the
      femoral head center and below the superior margin of the acetabulum accurately
      predicts an ideal puncture site. Thus, routine fluoroscopic guidance should be
      considered. Cathet Cardiovasc Intervent 2001;53:289-295.

PMID- 11458403
TI  - Impact of abciximab versus eptifibatide on length of hospital stay for PCI
      patients.
AB  - The purpose of this study is to compare the profile of percutaneous coronary
      intervention (PCI) patients who receive abciximab versus eptifibatide, as well as
      to compare the effect of abciximab versus eptifibatide on hospital length of
      stay. Retrospective data were obtained from HCIA's Clinical Pathways Database on
      5,446 coronary angioplasty patients who were administered either abciximab or
      eptifibatide. Estimation was conducted via a two-stage sample selection model. In
      the first stage, a probit regression was employed to determine which factors were
      associated with a higher probability of being administered abciximab versus
      eptifibatide. In the second stage, a negative binomial model was used to estimate
      the impact of a wide range of factors (selection of GPIIb/IIIa, patient
      demographics, insurance provider, health conditions, admission information, and
      hospital characteristics) on total hospital length of stay, as well as on
      postprocedural length of stay. After controlling for high-risk indications and
      other sources of selection bias, results indicate that receipt of abciximab was
      associated with a significantly shorter length of total hospital stay (0.83 fewer
      days; P < 0.001) than receipt of eptifibatide. Additionally, receipt of abciximab
      was found to be associated with a significantly shorter postprocedural hospital
      length of stay (0.48 fewer days; P = 0.002) compared to receipt of eptifibatide.
      Results of this study indicate that PCI patients who are administered abciximab
      versus eptifibatide have a significantly shorter length of hospital stay (both
      total and postprocedural). This finding is important since hospital length of
      stay reflects the occurrence of complications and has been found to be directly
      related to the resources consumed during in-patient management of patients.
      Cathet Cardiovasc Intervent 2001;53:296-303.

PMID- 11458404
TI  - Glycoprotein IIb/IIIa inhibitors: more different than alike?

PMID- 11458405
TI  - Percutaneous coronary interventions using a new 5 French guiding catheter:
      results of a prospective study.
AB  - The aim of this prospective study was to analyze the technical feasibility, the
      success rate, and the special complications of percutaneous coronary
      interventions (PCIs) using a newly released 5 Fr guiding catheter with an inner
      diameter of 0.058". The study was performed in 150 consecutive patients subjected
      to coronary angioplasty. In 89% of the patients, the intervention was started
      with a 5 Fr catheter (JR4 or JL4); in 16 patients a 6 or 7 Fr catheter was used
      because of unstable clinical conditions according to the decision of the
      interventional cardiologist. In 12 out of 134 patients, the guiding catheter had
      to be changed during the intervention from 5 Fr to a 6 or 7 Fr catheter due to
      poor backup support. In 112 out of 118 patients, the intervention was
      successfully performed using a 5 Fr catheter (95%); in 12 out of 16 patients,
      after changing the guiding catheter, the overall success rate was 93%. In
      patients with type A and B lesions who were initially treated using a 5 Fr
      catheter, the procedural success rate was 100% (81 out of 81), whereas in
      patients with type C lesions the procedural success rate was 83% (43 out of 53; P
      = 0.000053, Fisher's exact test). Furthermore, in patients with a diameter
      stenosis < 90%, the procedural success rate was 100% (57 out of 57), whereas in
      patients with a diameter stenosis of 90%-100%, the procedural success rate was
      87% (67 out of 77; P = 0.0050). Stent implantation was performed successfully in
      24 patients (18%) using the 5 Fr guiding catheter. This study confirms that PCI
      was technically feasible using a 5 Fr guiding catheter in the majority of
      consecutive patients with a success rate of 95%. There were significant
      differences in the success rate depending on the lesion type and the diameter
      stenosis. Complications were very rare and were not related to the guiding
      catheter. Limitations of the 5 Fr guiding catheters arose mainly from a poor
      backup support in long lesions and severe stenosis. Cathet Cardiovasc Intervent
      2001;53:308-312.

PMID- 11458406
TI  - Bigger might not always be better.

PMID- 11458407
TI  - Acute and long-term outcomes of stenting in coronary vessel > 3.0 mm, 3.0-2.5 mm,
      and < 2.5 mm.
AB  - We compared the acute and long-term outcomes of stentings in coronary vessels >
      3.0 mm, 3.0-2.5 mm, and < 2.5 mm. A total of 1,152 patients underwent coronary
      stenting was divided into three groups based on the reference vessel size. Group
      A consisted of 598 patients (667 lesions) with a reference vessel diameter > 3.0
      mm, group B 485 patients (544 lesions) with a reference vessel diameter of 3.0
      2.5 mm, and group C 114 patients (119 lesions) with a reference vessel diameter <
      2.5 mm. The procedural success, stent thrombosis, and in-hospital cardiac event
      rate were similar in the three groups. At 6-month angiographic follow-up, the
      lesion restenotic rate was significantly higher in the small-vessel group (14%,
      22%, and 26% in groups A, B, and C, respectively; P = 0.011). These differences
      appeared to result from a lesser acute gain and a lesser net gain in small-vessel
      group; the late luminal loss was similar in the three groups. During a follow-up
      duration of 28 +/- 3 months, group C patients had a significantly lower rate of
      event-free survival than the group A and B patients (71% vs. 85% and 82%; P =
      0.002). Stepwise regression analysis demonstrated that complex lesion (P = 0.032)
      and long lesion (P = 0.046) are independent predictors of restenosis in very
      small-vessel (< 2.5 mm) stenting. In conclusion, the acute results of stenting in
      small coronary arteries appear safe and feasible with a high procedural success
      rate and a low incidence of stent thrombosis. Stenting in patients with a small
      coronary artery appears to have a similar in-hospital cardiac event rate, but a
      higher angiographic restenosis rate and a lower event-free survival rate,
      compared to stenting in patients with a larger coronary artery. The predictors of
      restenosis in very-small-vessel stenting are complex lesions and long lesions.
      Cathet Cardiovasc Intervent 2001;53:314-322.

PMID- 11458408
TI  - Characterization of ultrasound-detected cerebral microemboli in patients
      undergoing cardiac catheterization using an in vitro middle cerebral artery
      model.
AB  - Cerebral embolization has been documented as one of the complications of
      diagnostic heart catheterization by transcranial Doppler (TCD). This study aimed
      to evaluate our hypothesis that the nature of embolic signals involved in
      different stages of catheter manipulation may be distinct. TCD-detected cerebral
      emboli occurring at different phases of cardiac catheterization were registered
      and differentiated by comparing their acoustic signatures with the Doppler
      signals generated from clinically frequently encountered embolic materials in an
      in vitro middle cerebral artery model. We found that there was a significant
      difference in embolic signal intensity and duration between different phases of
      cardiac catheterization. Our data suggest that different types of emboli may be
      involved in different phases of the catheterization. Cathet Cardiovasc Intervent
      2001;53:323-330.

PMID- 11458409
TI  - Significance of balloon imprint during coronary angioplasty.
AB  - Balloon imprint during angioplasty is often seen, but not at all inflations. We
      prospectively studied 235 consecutive patients undergoing 282 PTCAs during a 4
      month period, who were divided into two groups: those with balloon imprint during
      inflation (159 patients, 190 lesions; 67%) and those without (76 patients, 92
      lesions; 33%). Clinical and lesion characteristics and immediate outcome were
      compared. Patients undergoing urgent PTCA had less balloon imprint than those
      undergoing nonurgent PTCA (14.2% vs. 28.3%; P < 0.005). Although not reaching
      statistical significance, younger patients and diabetic patients tended toward
      less balloon imprint (P < 0.06). Patients with observed imprint had less visible
      thrombus at lesion site (31.1% vs. 42.4%; P < 0.05), and a tendency without
      statistical significance toward more dissections but less acute closure was
      observed (P < 0.07). In addition, more stents were implanted in the imprint group
      (79.5% vs. 66.3%; P < 0.02). Patients needing pressure > 6 atm to break the
      imprint had more eccentric lesions (68% vs. 27.1%; P < 0.000) and more
      dissections (13.9% vs. 5.1%; P < 0.03) than those needing lower pressure. Patient
      and lesion characteristics may determine the appearance of balloon imprint at
      PTCA, which in turn influences the procedure and its immediate outcome. Cathet
      Cardiovasc Intervent 2001;53:331-333.

PMID- 11458410
TI  - Three-year follow-up after rotational atherectomy for the treatment of diffuse in
      stent restenosis: predictors of major adverse cardiac events.
AB  - Restenosis remains the major limitation of coronary stent implantation,
      especially in diffuse forms of in-stent restenosis. In this study, rotablation
      (RA) with adjunct angioplasty of in-stent restenosis was performed in 84
      patients. Clinical follow-up and control angiography were obtained 6-month
      postprocedure. The rate of recurrent restenosis after rotablation for in-stent
      restenosis at 6-month angiographic follow-up was 45%, resulting in a rate of
      major adverse cardiac events of 35%. At 3-year follow-up, the cumulative event
      free survival rate was 57% for the entire population. The only predictor of MACE
      at 3-year clinical follow-up by multivariate logistic regression analysis was in
      stent lesion length. RA for the treatment of diffuse in-stent restenosis is
      thereby characterized by high procedural success rates and recurrent angiographic
      restenosis in 45% of patients with diffuse lesions. Major adverse cardiac events
      occur most likely within the first 6 months postprocedure. Three years after
      rotablation of in-stent restenosis, 43% of patients had experienced at least one
      major adverse cardiac event. Cathet Cardiovasc Intervent 2001;53:334-340.

PMID- 11458411
TI  - Use of fenoldopam to prevent radiocontrast nephropathy in high-risk patients.
AB  - We evaluated the ability of fenoldopam, a newly available renal vasodilator, to
      prevent radiocontrast nephropathy in high-risk patients undergoing interventional
      diagnostic and therapeutic angiographic procedures. We reviewed the results from
      46 consecutive procedures in patients with serum creatinine > or = 1.5 mg/dL if
      diabetic and > or = 1.7 mg/dL if nondiabetic. We compared our results to a
      previously published cohort of similarly at-risk patients. The incidence of
      radiocontrast nephropathy, defined as an increase in serum creatinine of > or =
      25% at 48 hr following the procedure, was 13% in the group treated with
      fenoldopam, compared to an expected 38%. The percentage change in serum
      creatinine at 48 hr was +16% vs. +118%, respectively, in the two groups. In this
      preliminary experience, the use of fenoldopam in high-risk patients appears to
      minimize the likelihood of radioncontrast nephropathy. Cathet Cardiovasc
      Intervent 2001;53:341-345.

PMID- 11458412
TI  - Use of ICHOR-platelet works to assess platelet function in patients treated with
      GP IIb/IIIa inhibitors.
AB  - Platelet glycoprotein GP IIb/IIIa inhibitors have been recently approved for use
      in treating patients with acute coronary syndromes and those undergoing PCI. The
      purpose of this study was to assess the feasibility of using a new device, the
      ICHOR platelet works, to detect platelet inhibition in patients undergoing PCI
      and treated with abciximab or tirofiban. The study was conducted at Baylor
      College of Medicine, Houston, Texas. Thirty patients undergoing PCI and treated
      with abciximab (n = 10) or tirofiban (n = 20) are included. Blood samples were
      obtained before, at 30 min, at 4 hr, and at 12 hr after starting the GP IIb/IIIa
      inhibitors and 2 hr after discontinuation. Baseline studies revealed > 95%
      platelet aggregability in all patients after exposure to ADP (20 microM). After
      starting tirofiban, 82%, 83%, and 82% of platelets were inhibited at 30 min, 4
      hr, and 12 hr. Platelet inhibition decreased to 43% 2 hr after discontinuation of
      tirofiban. Similarly, ICHOR platelet works detected 91%, 92%, and 85% platelet
      inhibition at 30 min, 4 hr, and 12 hr after starting abciximab, respectively.
      Platelet inhibition decreased to 73% 2 hr after discontinuation. The ICHOR
      platelet works is a promising, simple, and rapid bedside method that may have
      clinical utility in assessing platelet inhibition in patients treated with GP
      IIb/IIIa inhibitors. Cathet Cardiovasc Intervent 2001;53:346-351.

PMID- 11458413
TI  - Noninvasive detection of coronary lesions by multislice computed tomography:
      results of the New Age pilot trial.
AB  - The reliable noninvasive assessment of coronary artery disease would constitute
      an important step forward in clinical cardiology. The aim of the New Age pilot
      trial was to evaluate the diagnostic accuracy of multislice computed tomography
      (MSCT) in determining coronary lesions. As a gold standard for in vivo plaque
      detection, intracoronary ultrasound (ICUS) was used. Forty plaques were detected
      by ICUS in 15 target vessels (LAD, n = 8; RCA, n = 7) in patients assigned for
      ICUS-guided PTCA. Preinterventional MSCT was performed in all patients and the
      results were compared to ICUS with regard to lesion detection and quantification.
      According to ICUS results, the 40 plaques were divided into three groups: group
      I, mild lesions < 50% (n = 14; 44.36% +/- 5.77%); group II, intermediate lesions
      50%-75% (n = 12; 59.18% +/- 9.39%); and group III, severe lesions > 75% (n = 14;
      91.47% +/- 3.68%). All MSCT scans showed sufficient image quality for analysis.
      Thirty of 40 (75%) plaques were detected by MSCT in a first blinded session.
      After unblinding the ICUS results, the remaining 10 (25%) plaques could be
      identified. Lesion severity was classified correctly in 34 of 40 (85%) plaques.
      Plaque calcifications were diagnosed correctly in 16 of 19 (84.2%) plaques.
      Quantification of vessel size revealed a good correlation to the ICUS results
      (r(2) 0.68; P = 0.004). Noninvasive MSCT angiography showed good diagnostic
      accuracy with regard to lesion detection and quantification of vessel size. The
      overall good image quality, makes this new technology a promising modality, which
      might become an alternative diagnostic approach in patients with known or
      suspected coronary artery disease. Cathet Cardiovasc Intervent 2001;53:352-358.

PMID- 11458414
TI  - Angiographic analysis of immediate and long-term results of PTCR vs. PTCA in
      complex lesions (COBRA study).
AB  - We conducted a prospective, randomized trial to compare immediate and long-term
      effects of percutaneous transluminal coronary angioplasty (PTCA) and high
      frequency rotational atherectomy (PTCR) in patients with angiographically
      predefined complex coronary artery lesions (AHA type B2 and C). The relation of
      lesion characteristics to procedural results is reported in this angiographic
      analysis. Patients were randomly assigned to balloon angioplasty (n = 250
      patients) or rotational atherectomy (n = 252 patients). Quantitative coronary
      angiography could be performed in 447 patients to evaluate immediate results and
      in 293 patients with a 6-month angiographic follow-up. Procedural success was
      comparable in the PTCR and in the PTCA group (80% vs. 76%, P = 0.260). The need
      for stent implantation due to a residual stenosis >50% or a bail-out situation
      was significantly higher in the PTCA group (9.7% vs. 2.0%, P = 0.001). In both
      treatment groups, diameter stenosis was effectively reduced and MLD increased.
      The acute gain did not differ between the two groups. At 6-month control, the
      restenosis rate was comparable in the PTCR and in the PTCA group (37% vs. 35%, P
      = 0.658), whereas diameter stenosis was significantly more severe in the PTCR
      group than in the PTCA group (52% vs. 46%, P = 0.039) and, correspondingly, the
      MLD was significantly smaller in the PTCR group (1.29 mm vs. 1.44 mm, P = 0.031).
      Late loss was about the same in both groups, however, net gain and net gain index
      were significantly higher in the PTCA group (0.82 mm vs. 0.64 mm, P = 0.008; and
      31% vs. 24%, P = 0.009). Analysis of procedural results for various lesion
      characteristics revealed no significant difference between treatment groups. In
      this randomized trial, complex coronary artery lesions were treated with
      comparable results for angiographic and procedural success and the restenosis
      rate by both, PTCA and PTCR. Late loss, however, was significantly higher and net
      gain significantly smaller after PTCR. Stents, although infrequently used, had a
      relevant impact on immediate PTCA results but not on late results. Cathet
      Cardiovasc Intervent 2001;53:359-367.

PMID- 11458415
TI  - Timing and long-term benefit.

PMID- 11458416
TI  - The puncture technique: a new method for transcatheter closure of patent foramen
      ovale.

PMID- 11458417
TI  - Transcatheter closure of atrial septal defect using Amplatzer septal occluder in
      Chinese adults.
AB  - Amplatzer septal occluder (AGA Med. Co., USA) is a novel device for occlusion of
      atrial septal defect. We present our experience of transcatheter closure of
      atrial septal defects using Amplatzer septal occluder in 45 adult Chinese
      patients (age range 18-69 years). The size of atrial septal defect varied from 14
      28 (23 +/- 4) mm. Cardiac catheterization revealed a pulmonary-to-systemic shunt
      ratio ranging from 1.4-2.8 (mean 2.0 +/- 0.4). The procedure was successful in 44
      (98%) patients. Displacement of the device requiring surgical removal occurred in
      one (2%) patient and minor wound complication occurred in two (4%) patients.
      Total procedure time was 67 +/- 16 minutes and the fluoroscopy time was 25 +/- 8
      min. Immediate post-procedure and pre-discharge echocardiography revealed
      complete abolition of shunt in 42 (93%) and trivial residual shunt in 3 (7%)
      patients. The average follow-up period was 16 +/- 6 months (range 2 months to 3
      years) months. None of the patients had developed other major complication at
      follow-up. Cathet Cardiovasc Intervent 2001;52:373-377.

PMID- 11458418
TI  - Transcatheter closure of the atrial septum: it's been a long strange trip.

PMID- 11458419
TI  - Combined right transradial coronary angiography and selective carotid
      angiography: safety and feasibility in unselected patients.
AB  - We evaluated the safety and feasibility of ad hoc carotid angiography following
      the right transradial coronary angiography. Selective carotid angiography was
      performed subsequent to coronary angiography in 213 consecutive patients. A 5 Fr
      Simmons catheter was reformed in descending or ascending aorta, then, withdrawn
      and rotated to cannulate the left and right carotid artery. Both carotid
      angiography was performed selectively in 211 (99%) patients. In two patients with
      severely tortuous subclavian artery, selective cannulation of the left carotid
      artery failed. There was no thromboembolism or arterial dissection. After the
      learning phase of 50 patients, the time to reform the catheter in aorta and to
      cannulate the left and right carotid artery was 50 +/- 77, 66 +/- 68, and 58 +/-
      57 sec, respectively. Total procedural time was 195 +/- 145 sec. In conclusion,
      ad hoc carotid angiography can be performed reliably and safely following the
      right transradial coronary angiography. It might be useful for evaluation of an
      isolated or associated carotid artery stenosis. Cathet Cardiovasc Intervent
      2001;53:380-385.

PMID- 11458420
TI  - Morphological variations of secundum-type atrial septal defects: feasibility for
      percutaneous closure using Amplatzer septal occluders.
AB  - The aim of the study was to assess the morphology of secundum-type atrial septal
      defects (ASD) with a view to percutaneous closure using Amplatzer septal
      occluders (ASO). One hundred and ninety patients who underwent closure of
      isolated secundum-type ASD between September 1995 and January 2000 were included.
      The morphology of the defects was studied using transthoracic and transesophageal
      echocardiography. Patients with defects of suitable morphology and size underwent
      percutaneous closure using ASO. The remaining patients underwent surgical
      closure. Centrally placed defects were observed in 46 patients (24.2%).
      Morphological variations of secundum-type ASD were detected in 144 patients
      (75.8%). One hundred and fifty-one patients (79.5%) underwent percutaneous
      closure using ASO. Thirty-nine patients (20.5%) underwent surgical closure.
      Centrally placed defects, defects with deficient superior anterior rim, multiple
      defects, and perforated aneurysms of the interatrial septum are morphological
      variations of secundum-type ASD suitable for percutaneous closure using ASO.
      Cathet Cardiovasc Intervent 2001;53:386-391.

PMID- 11458421
TI  - Inferior vena cava occlusion catheter for pediatric patients with heart disease:
      for more detailed cardiovascular assessments.
AB  - Traditional evaluation of cardiac function is too often limited by reliance on
      measurements with complex interdependence between cardiac properties and loading
      factors. Analysis by ventricular pressure-volume (P-V), -area (P-A), or 
      dimension (P-D) relations during inferior vena caval (IVC) occlusion
      independently quantifies ventricular properties and loading conditions, providing
      detailed information about cardiovascular dynamics. However, there has been no
      appropriate size of balloon catheter that can effectively occlude IVC of
      pediatric patients, hindering the application of P-V (P-A, or P-D) analysis to
      children with heart disease despite its potential benefit. To address this
      problem, we have developed a new balloon catheter for IVC occlusion in children.
      The catheter effectively occluded IVC in 92 pediatric patients with varying forms
      of heart disease who underwent cardiac catheterization, yielding end-systolic
      pressure-area relations. Thus a newly developed balloon catheter would contribute
      to establishing more accurate and detailed cardiovascular assessments in children
      with heart disease. Cathet Cardiovasc Intervent 2001;53:392-396.

PMID- 11458422
TI  - IVC occlusion catheter: works well but will it be widely applied?

PMID- 11458423
TI  - Transcatheter closure of large persistent left superior vena cava causing
      cyanosis in two patients post-Fontan operation utilizing the Gianturco Grifka
      vascular occlusion device.
AB  - We report the successful transcatheter closure of a large persistent left
      superior vena cava draining into the pulmonary venous circulation causing
      cyanosis in two patients who had previously undergone the Fontan operation
      utilizing the Gianturco Grifka vascular occlusion device. Cathet Cardiovasc
      Intervent 2001;53:398-404.

PMID- 11458424
TI  - Amplatzing a 6 Fr Judkins right guiding catheter for increased success in complex
      right coronary artery anatomy.
AB  - Stent supported angioplasty is being performed in an increasing number of
      patients and, with advances in device technology, more morphologically complex
      lesions are being treated. In such a setting, it is extremely important to
      deliver the device to the target lesion. We describe a new technique that allows
      successful stent delivery in complex right coronary anatomy using the Judkins
      right guiding catheter. Cathet Cardiovasc Intervent 2001;53:405-409.

PMID- 11458425
TI  - Percutaneous ulnar artery approach for coronary angiography: a preliminary report
      in nine patients.
AB  - The radial artery approach is becoming more popular for diagnostic cardiac
      catheterization and interventional procedures because of its lower incidence of
      access site complications and decreased patient discomfort after the procedure.
      However, Allen's test reveals inadequate blood supply through the ulnar artery to
      the hand, and therefore the approach does not seem to be suitable in 10%-30% of
      patients. Here we demonstrated a new percutaneous ulnar artery approach for
      coronary angiography in nine patients. We succeeded in obtaining an entry site
      into the left ulnar artery in seven patients. The average time for cannulation
      and that for catheterization procedure were comparable with those of the radial
      approach previously reported from other laboratories. Complications such as
      bleeding, loss of an ulnar pulse, ulnar nerve injury, and the formation of an
      aneurysm or fistula were not observed in any patient. The ulnar approach may be
      another technique that decreases patient discomfort and risk, while preserving
      the radial artery as a potential coronary bypass graft for surgical myocardial
      revascularization. Cathet Cardiovasc Intervent 2001;53:410-414.

PMID- 11458426
TI  - Inadvertent stent extraction six months after implantation by an entrapped
      cutting balloon.
AB  - We report a case of extraction of a restenosed aorto-ostial stent by an entrapped
      cutting balloon that had inadvertently been passed through a protruding stent
      cell. Cathet Cardiovasc Intervent 2001;53:415-419.

PMID- 11458427
TI  - A comparison of four stent designs on arterial injury, cellular proliferation,
      neointima formation, and arterial dimensions in an experimental porcine model.
AB  - The stent-artery interactions of different stent designs have implications for
      their clinical effects. We studied four different stent designs to compare their
      effects on arterial injury, cellular proliferation, neointima formation, and
      arterial dimensions. Eighteen nonatherosclerotic miniswine underwent random
      placement of 52 coronary stents (3.0 mm), including self-expanding nitinol stents
      (no postdilation; Radius, n = 13) and balloon-expandable stents (8 atm x 45 sec;
      Palmaz-Schatz, n = 13; BX, n = 12; and Multilink, n = 14). Cellular proliferation
      was determined by S-phase labeling with BrdU at 7, 14, and 28 days.
      Proliferation, injury scores, and arterial morphometry were blindly evaluated.
      All four stent designs had similar injury scores, cellular proliferation indexes
      (neointimal and medial), and adventitial areas. Nitinol stents resulted in a
      twofold increase in neointimal area and thickness in 28-day vessels (P = 0.002).
      However, lumen area was similar for all stent designs because of an offsetting
      expansion in vessel area in nitinol stents (20% greater than balloon-expandable
      stents) occurring between 7 and 14 days after stent deployment (P = 0.03).
      Reduced neointimal cell density in nitinol stents (20% less than balloon
      expandable stents, P = 0.012) suggests that extracellular matrix expansion
      accounts for the larger neointima in nitinol stents. Self-expansion of nitinol
      stents within normal porcine arteries results in a similar degree of arterial
      injury compared to balloon-expandable stent designs. Progressive enlargement of
      nitinol stents between 7 and 14 days after deployment is associated with the
      development of a larger, matrix-rich neointima, with a preserved lumen area.
      Cathet Cardiovasc Intervent 2001;53:420-425. Published 2001 Wiley-Liss, Inc.

PMID- 11458428
TI  - "Metaling" with new stent designs.

PMID- 11458429
TI  - Intramyocardial delivery of FGF2 in combination with radio frequency
      transmyocardial revascularization.
AB  - Therapeutic angiogenesis and percutaneous transmyocardial revascularization (PMR)
      are potentially synergistic modalities to improve myocardial perfusion. To
      evaluate the efficiency of FGF2 delivery into an area that has been radio
      frequency (RF) ablated, we studied two catheter-based delivery methods, a direct
      injection system (Stiletto) and a combined RF ablation-delivery system (RF-PMR).
      Four groups (n = 3/group) of pigs received six transendocardial injections of
      (125)I-FGF2/fluorescent microspheres with either the Stiletto or the RF-PMR
      catheter. RF-PMR injections were preceded by a 0.6 sec RF ablation step. After
      either 1 or 24 hr, hearts and other tissues were harvested. Intramyocardial
      deposition sites were located with UV light and isolated. Specific activity per
      site was expressed as a percentage of total activity injected per site corrected
      for quenching. Injection site recovery was high for both catheter systems
      (average = 88%) and systemic uptake was low (< 6% in the liver). FGF2 retention
      was significantly higher with the Stiletto than the RF-PMR catheter (Stiletto 1
      hr 41% +/- 17%, 24 hr 26% +/- 10%, RF-PMR 1 hr 21% +/- 14%, 24 hr 13% +/- 8%; P <
      0.001), principally explained by the differences in catheter design. The Stiletto
      has a retractable needle and is optimized for intramyocardial delivery, whereas
      infusion from the RF-PMR device occurs at the endocardial surface and relies on
      channels created during RF ablation. Overall, FGF2 retention after
      transendocardial intramyocardial delivery by the Stiletto or the RF-PMR system is
      significantly higher than previously observed for intracoronary, intravenous and
      intrapericardial delivery. In conclusion, the combination of RF ablation and
      growth factor delivery using the RF-PMR system is feasible and efficient. Cathet
      Cardiovasc Intervent 2001;53:429-434.

PMID- 11458430
TI  - Intravascular radiation: let's not let a promising therapy go unfulfilled.

PMID- 11458431
TI  - Paracetamol and asthma.

PMID- 11458432
TI  - [XXIth Forum on Cancer. Paris, France, 6-8 June 2001. Abstracts].

PMID- 11458433
TI  - [The editor does not dismiss].

PMID- 11458434
TI  - [Non-invasive diagnosis of emphysema: defining the present position].

PMID- 11458435
TI  - [Non-invasive definition of dimensions of peripheral lung structures via aerosol
      morphometry: present knowledge and perspectives].

PMID- 11458436
TI  - [The impact of different definitions of hypoxemia on the relation between awake
      pulmonary pressure and hypoxemia during sleep in patients with COPD].
AB  - BACKGROUND: Sleep related hypoxemia (SRH) in chronic obstructive pulmonary
      disease (COPD) can be easily detected by pulse-oximetry and may contribute to the
      development of pulmonary hypertension (PH). Since several parameters for the
      quantification of SRH are in use, we investigated which of these parameters has
      the strongest relation to the awake pulmonary arterial pressure (PAP) and is able
      to distinguish between patients without and with PH. PATIENTS AND METHODS: 44
      COPD-patients (awake PaO2 > or = 60 mm Hg) were investigated. PAP at rest (PAP;
      pathological threshold > 20 mm Hg) and under physical exercise (PAPB; p.t. > 28
      mm Hg) were determined during daytime by Swan-Ganz-catheter. To quantify the
      degree of SRH the following parameters of nocturnal pulse-oximetry were used:
      mean nocturnal oxygen saturation (SaO2 m; p.t. < 90%), nadir SaO2 (SaO2 min; p.t.
      < 85%), and mean time of SaO2 < or = 90% in relation to total time of
      registration (t90; p.t. > 30%). Linear correlations and regressions as Chi 2
      respectively Fisher-test were used for statistical analysis (p < 0.05). RESULTS:
      Generally there was only a weak relation between PAP and SRH. The best linear
      correlation at rest respectively under physical exercise was found between PAP
      and SaO2 min (r = -0.529 resp. -0.541, p < 0.001). Using the above defined
      thresholds for PAP and SaO2 patients could be most precisely separated into those
      without and with PH using SaO2 min with a threshold for the pathological range of
      < 85% (p = 0.030 resp. 0.002). t90 with a threshold > 30%, however, had a much
      worse selectivity (p = 0.487 resp. 0.057). CONCLUSIONS: In COPD-patients with SRH
      the closest relation can be found between nadir SaO2 and PAP resp. PAPB.
      Furthermore nadir SaO2 (< 85%) could more precisely separate patients into those
      without and with pulmonary hypertension than t90. The overall weak relation
      between nocturnal oxygenation and pulmonary hypertension shows, however, that
      other factors such as daytime PaO2, hypercapnia or emphysema are involved in the
      development of pulmonary hypertension in COPD.

PMID- 11458437
TI  - [Obstructive sleep apnea and cardiovascular diseases--hypothesis on the
      pathophysiological interlinks].

PMID- 11458438
TI  - [Primary pulmonary manifestation of extramedullary acute myelocytic leukemia].
AB  - We report on a 49 year old female with primary extra-medullary manifestation of a
      acute myeloid leukemia in the lungs without leukemic signs. The disease was
      diagnosed by detection of leukemic blast cells in bronchoalveolar lavage.
      Chemotherapy with the TAD-VP-scheme resulted in partial remission. The patient
      died in systemic early relapse. To our knowledge this is the first description of
      primary isolated extra-medullary manifestation of a acute myeloid leukemia in the
      lungs.

PMID- 11458439
TI  - [Efficacy of demand oxygen delivery systems in patients with chronic obstructive
      lung disease].
AB  - To maintain mobility in patients with chronic hypoxemia who are under long-term
      oxygen therapy, portable oxygen systems are available. They have the disadvantage
      of a short range. To prolong the range and to reduce the cost of oxygen
      treatment, demand oxygen delivery systems (DODS) are used. Aim of the study was
      to compare three DODS (DOC-2000 [D], TransTracheal Inc.; Oxytron [O], Weinmann;
      Pulsair [P], DeVilbiss, Sunrise Medical) with continuous oxygen delivery. 17
      patients (age 67.82 +/- 9.46 years; FEV1 1.23 +/- 0.69 l; PaO2 48.8 +/- 6.7 mm
      Hg) were studied. The continuous flow oxygen (CONT) and the DODS were applied to
      the patients for 30 minutes each in random sequence with an airflow of 2 l/min.
      After 15 and 30 minutes arterial blood gas analysis was done. Oxygen saturation
      was recorded continuously by pulseoximetry. After 15 minutes no significant
      differences in PaO2 were found between CONT and DODS. After 30 minutes no
      significant difference in PaO2 was found in CONT as compared to P. Significant
      lower PaO2 values were found for O and D as compared to CONT (p < 0.01). With P
      the range of a portable oxygen source was increased by 161.5 percent, with O by
      172 percent, with D the range was increased by only 17.2 percent. Prolongation of
      range of a portable oxygen source can be achieved by means of DODS without a
      decrease of PaO2 and thus without loss of quality of the oxygen treatment.
      However, there are differences in efficacy between the DODS.

PMID- 11458440
TI  - [Acetylsalicylic acid and bioptic methods in pneumology].

PMID- 11458441
TI  - [Are pulmonary Candida infections a reality?].

PMID- 11458442
TI  - Biodisposition of FITC-labeled aloemannan in mice.
AB  - Biodisposition of FITC-labeled aloemannan (F-AM) with the homogenate from some
      organs in mice was demonstrated. F-AM was metabolized only by the mucosa from the
      large intestine into smaller molecules that were effectively absorbed in mice.
      The homogenate from the other tissues did not affect the metabolism of F-AM. The
      degraded product (1) of F-AM after incubation with 10% feces homogenate for 24 h
      was chromatographed on a highly porous polymer and a Sephadex LH-20 column to
      provide an FITC-degraded fraction (2), which was shown to have a molecular weight
      of 800 D on Sephadex G-25 gel permeation. Metabolite 2 was examined by
      physicochemical methods and shown to be a mixture of FITC-hexose and -2 hexose on
      FAB-MS. An FITC-degraded fraction (3) with a molecular weight of 3 KD was
      obtained by 6-h incubation with 10% feces homogenate on Sephadex G-25 column
      chromatography and was shown to be a mixture of FITC-9 and 12 x hexose on TOF-MS.

PMID- 11458443
TI  - In vitro anti-HIV activity of sulfated cell-wall polysaccharides from gametic,
      carposporic and tetrasporic stages of the Mediterranean red alga Asparagopsis
      armata.
AB  - The gametic, carposporic and tetrasporic reproductive stages from the
      Mediterranean red alga Asparagopsis armata contain peculiar sulfated galactans
      with galactose:3,6-anhydrogalactose:sulfates molar ratio of 1:0.01:1.23,
      1:0.04:0.47 and 1:0.01:1.13, respectively. These water-soluble polysaccharides
      were studied for their in vitro activity against the human immunodeficiency virus
      (HIV-1). Gametic and tetrasporic galactans inhibit HIV replication at 10 and 8
      micrograms/ml, respectively, as measured by HIV-induced syncitium formation as
      well as reverse transcriptase activity in cell-free culture supernatant. The
      carposporic polysaccharide is ineffective, even at 100 micrograms/ml. The maximal
      antiviral effect involves the presence of the polysaccharides after or during
      infection but not before infection. This time of action suggests an inhibition of
      an early step of HIV infection.

PMID- 11458444
TI  - Interaction of various Piper methysticum cultivars with CNS receptors in vitro.
AB  - Methanolic leaf and root extracts of the Hawaiian kava (Piper methysticum Forst.)
      cultivars, Mahakea, Nene, Purple Moi and PNG, were tested on binding affinities
      to CNS receptors including GABAA (GABA and benzodiazepine binding site), dopamine
      D2, opioid (mu and delta), serotonin (5-HT6 and 5-HT7) and histamine (H1 and H2).
      HPLC analysis was carried out in order to determine the amount of the main
      kavalactones kavain, 7,8-dihydrokavain, methysticin, 7,8-dihydromethysticin,
      yangonin and 5,6-demethoxyyangonin. The most potent binding inhibition was
      observed for leaf extracts to GABAA receptors (GABA binding site) with IC50
      values of approximately 3 micrograms/ml, whereas root extracts were less active
      with IC50 values ranging from 5 micrograms/ml (Nene) to 87 micrograms/ml
      (Mahakea). Since the leaf extracts generally contained lower amounts of the
      kavalactones than the root extracts, there might exist additional substances
      responsible for these activities. Leaf extracts also inhibited binding to
      dopamine D2, opioid (mu and delta) and histamine (H1 and H2) receptors more
      potently than the corresponding root extracts with IC50 values ranging from 1 to
      100 micrograms/ml vs. > or = 100 micrograms/l, respectively. Significant
      differences in the potential of binding inhibition were also observed between
      cultivars. Binding to serotonin (5-HT6 and 5-HT7) and benzodiazepine receptors
      was only weakly inhibited by both root and leaf extracts of all four cultivars.
      In conclusion, our investigation indicates that the GABAA, dopamine D2, opioid
      (mu and delta) and histamine (H1 and H2) receptors might be involved in the
      pharmacological action of kava extracts. Since the cultivars contained similar
      amounts of kavalactones, while their pharmacological activities differed
      markedly, other constituents may play a role in the observed activities.
      Additionally, leaves generally exhibited more potent binding inhibition than
      roots, therefore leaf of P. methysticum might be an interesting subject for
      further pharmacological studies.

PMID- 11458445
TI  - Lignans from the rhizomes of Coptis japonica differentially act as anti
      inflammatory principles.
AB  - Coptis japonica Makino (Ranunculaceae) is known to possess several biological
      activities such as anti-inflammatory effects. In this study, five lignans,
      isolariciresinol (1), lariciresinol glycoside (2), pinoresinol (3), pinoresinol
      glycoside (4) and syringaresinol glycoside (5), isolated from the rhizomes of C.
      japonica were tested to evaluate their in vitro anti-inflammatory effects.
      Pinoresinol and isolariciresinol showed higher inhibitory effects on TNF-alpha
      production, whereas syringaresinol glycoside strongly suppressed lymphocyte
      proliferation. The results indicate that the lignans may differentially modulate
      inflammatory cell responses, suggesting that these compounds may participate in
      anti-inflammatory processes by C. japonica.

PMID- 11458446
TI  - Relaxing effects of Ligstrum purpurascens extract and purified acteoside in rat
      aortic rings.
AB  - The present study describes the effects of an extract obtained from the leaves of
      Ligstrum purpurascens and acteoside purified from the extract on the contractile
      response to various agonists in rat isolated aortic rings. L. purpurascens
      extract relaxed 9,11-dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha
      (U46619)-preconstricted rings in a concentration-dependent manner (IC50: 0.14 +/-
      0.01 mg/ml with endothelium and 0.16 +/- 0.01 mg/ml without endothelium). The
      extract also reduced contraction induced by 35 mM K+ or by 1 microM phorbol 12,13
      diacetate (PDA) in endothelium-intact rings. The extract (0.1-0.3 mg/ml) reduced
      the concentration-response to U46619 in normal Krebs solution or to CaCl2 in 35
      mM K(+)-containing solution. Acteoside accounts for 2.05% of total L.
      purpurascens extract in weight. Acteoside induced relaxation of rings
      preconstricted by U46619 (IC50: 0.22 +/- 0.01 mg/ml) but it caused an increase in
      35 mM K(+)-induced tone. Removal of endothelium enhanced the relaxing effect of
      acteoside. Besides, pretreatment with acteoside inhibited endothelium/nitric
      oxide-mediated relaxation induced by acetylcholine. These results indicate that
      acteoside is unlikely the major ingredient responsible for the vasodilator effect
      of L. purpurascens extract. The extract relaxed the preconstricted aortic rings
      probably through multiple mechanisms by acting on smooth muscle cells. The
      inhibitory effect on endothelial nitric oxide-mediated relaxation suggests that
      acteoside could also act on the endothelial cells to reduce nitric oxide release.

PMID- 11458447
TI  - Studies on the hepatocyte protective activity and the structure-activity
      relationships of quinic acid and caffeic acid derivatives from the flower buds of
      Lonicera bournei.
AB  - 13 quinic acid derivatives along with caffeic acid, methyl caffeate, myo
      inositol, bis[5-formylfurfuryl] ether and 6,7-dihydroxycoumarin were isolated
      from the ethanol extract of the flower buds of Lonicera bournei Hemsl., among
      which 8 compounds were firstly obtained from this genus. The effects of different
      solvent soluble fractions of the ethanol extract and the pure compounds on
      heptocyte death induced by D-galactosamine (D-GalN)/tumor necrosis factor alpha
      (TNF-alpha) were studied, and the structure-activity relationships were also
      discussed.

PMID- 11458448
TI  - Complexation of Ginkgo biloba extract with phosphatidylcholine improves
      cardioprotective activity and increases the plasma antioxidant capacity in the
      rat.
AB  - The aim of this work was to compare in the rat the cardioprotective efficacy and
      the total plasma antioxidant activity of a standardised Ginkgo biloba L. extract
      (GB) as such (300 mg/kg/day) or complexed with phosphatidylcholine (GB-PC; 1:2
      w/w), after a 5 days oral administration. At the end of the treatment, the total
      plasma antioxidant defence was determined by the TRAP and FRAP assays, and the
      hearts from all groups of animals subjected to moderate ischemia (flow reduction
      to 1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min). The recovery of
      left ventricular developed pressure (LVDP) at the end of reperfusion was 35-40%
      of the preischemic values in both control and vehicle rats, 50.2% in the GB group
      and 72.5% in the GB-PC pre-treated animals. Creatine kinase (CK) outflow in the
      perfusate from the hearts of GB and GB-PC treated animals were restrained to a
      different extent vs. controls (by 71% GB-PC; by 22% GB); the rate of prostacyclin
      (6-keto-PGF1 alpha) release was far greater in GB-PC than in GB hearts. In
      parallel, the GB extract significantly increased the total antioxidant plasma
      capacity (by 24.5% TRAP; 27.9% FRAP) only when complexed with phospholipids. This
      indicates an increased bioavailability of phenolic antioxidants when suitably
      embedded within a lipophilic carrier. The results of this study demonstrate that
      complexation of Ginkgo biloba with phospholipids induces in the rat, even after a
      short treatment a greater resistance of the heart to ischemia/reperfusion damage
      in respect to the native extract, due to an increased plasma antioxidant
      activity.

PMID- 11458449
TI  - Effects of baicalein isolated from Scutellaria baicalensis Radix on adhesion
      molecule expression induced by thrombin and thrombin receptor agonist peptide in
      cultured human umbilical vein endothelial cells.
AB  - We examined the effects of various flavonoids isolated from the roots of
      Scutellaria baicalensis Georgi on adhesion molecule expression induced by
      thrombin and thrombin receptor agonist peptide (SFLLRNPNDKYEPF, TRAP) in cultured
      human umbilical vein endothelial cells. Thrombin and thrombin receptor agonist
      peptide induced endothelial leukocyte adhesion molecule-1 (ELAM-1) expression.
      Intercellular adhesion molecule-1 (ICAM-1) expression was also induced by
      thrombin, but not by TRAP. Baicalein isolated from Scutellariae Radix inhibited
      ELAM-1 expression induced by thrombin and thrombin receptor agonist peptide dose
      dependently, with 50% inhibitory concentrations (IC50) of 5.53 +/- 1.68 microM
      and 2.44 +/- 1.08 microM, respectively. Furthermore, baicalein inhibited thrombin
      induced ICAM-1 expression with an IC50 of 9.67 +/- 1.28 microM. In addition,
      baicalein inhibited the expressions of ELAM-1 and ICAM-1 stimulated by protein
      kinase C (PKC) activator phorbol myristate acetate (PMA).

PMID- 11458450
TI  - New antioxidant and antimicrobial ellagic acid derivatives from Pteleopsis
      hylodendron.
AB  - Bioassay-guided isolation of two new compounds, 3,4-methylenedioxy-3'-O-methyl-4'
      O-glucoside ellagic acid (1) and the pteleoellagic acid derivative (2), from the
      stem bark of Pteleopsis hylodendron is reported along with 3,4-methylenedioxy-3'
      O-methyl ellagic acid (3), 3,3'-di-O-methyl ellagic acid (4) and 3,3',4'-tri-O
      methyl ellagic acid (5), which were obtained for the first time from this plant.
      The structures of these compounds were elucidated with the help of spectroscopic
      studies. Compounds 1 and 4 were found to have significant antioxidant activity,
      while compounds 1-4 showed antibacterial activity against different pathogenic
      bacteria.

PMID- 11458451
TI  - Antiplasmodial and antioxidant isofuranonaphthoquinones from the roots of Bulbine
      capitata.
AB  - The roots of B. capitata yielded the new compounds 5,8-dihydroxy-1
      tigloylmethylnaphtho[2,3-c]furan-4,9-dione, 1-acetoxymethyl-8-hydroxynaphtho[2,3
      c]furan-4,9-dione, and 1-acetoxymethyl-5,8-dihydroxynaphtho[2,3-c]furan-4,9
      dione, in addition to the known compounds chrysophanol, 10,10'-chrysophanol
      bianthrone, 8-hydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1
      methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1-hydroxymethylnaphtho[2,3
      c]furan-4,9-dione, and 8-hydroxy-5-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione,
      or 5-hydroxy-8-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione. The new as well as
      the known isofuranonaphthoquinones showed antioxidant and weak antiplasmodial
      activities.

PMID- 11458452
TI  - Alkaloids and flavonoids from peanut skins.
AB  - Separation of the water-soluble fraction of peanut skins led to the isolation of
      8 flavonoids and two novel indole alkaloids. Two new flavonoid glycosides have
      been identified as isorhamnetin 3-O-[2-O-beta-glucopyranosyl-6-O-alpha
      rhamnopyranosyl]- beta-glucopyranoside and 3',5,7-trihydroxyisoflavone-4'-methoxy
      3'-O-beta-glucopyranoside. Two alkaloids are 2-methoxyl-3-(3-indolyl)-propionic
      acid and 2-hydroxyl-3-[3-(1-N-methyl)-indolyl]-propionic acid. These isolated
      flavonoids were evaluated for their free radical scavenging activity and protein
      glycation inhibitory effects.

PMID- 11458453
TI  - HIV inhibitor from Thai bitter gourd.
AB  - Thai bitter gourd protein (MRK29) was isolated from Momordica charantia ripe
      fruit and seed. The purification was performed by ammonium sulfate fractionation
      and gel filtration chromatography. MRK29 possessed one isoelectric point of (pI)
      > or = 9, and the time of flight mass spectrum (TOFMS) indicated its molecular
      weight at 28.6 kD. The twenty amino acid sequence from the N-terminus was in the
      following order: 1Asp Val Asn Phe Arg Leu Ser Gly Ala 10Asp Pro Arg X Tyr Gly Met
      Phe Ile Glu 20Asp. MRK29 inhibited the HIV-1 reverse transcriptase with 50% IR at
      the concentration of 18 micrograms/ml. MRK29 was concentrated in the 30-60% salt
      precipitated fraction, at which the concentration of 0.175 microgram/ml exerted
      82% reduction of viral core protein p24 expression in HIV-infected cells. MRK29
      might have modulatory role on immune cells, because it increased 3-fold TNF
      activity.

PMID- 11458454
TI  - Sesquiterpenoids from Magnolia grandiflora.
AB  - Three new sesquiterpenoids were obtained from the leaves of Magnolia grandiflora
      L. Their structures were determined as 6 alpha,11-dihydroxy-12,13-diacetoxyelem
      1,3-diene, 4 alpha,6 alpha,10 alpha-trihydroxy-13-acetoxyguaia-11-ene, and 12,13
      diacetoxyguaia-4 alpha,6 alpha,10 alpha,11-tetraol on the basis of spectral
      evidence. In addition, the known sesquiterpenoid magnograndiolide was also
      obtained.

PMID- 11458455
TI  - Costunolide, a sesquiterpene from the stem bark of Magnolia sieboldii, inhibits
      the RAS-farnesyl-proteintransferase.
AB  - Costunolide, a germacrane sesquiterpene lactone isolated from the stem bark of
      Magnolia sieboldii demonstrated a significant inhibition upon the farnesylation
      process of human lamin-B by farnesyl-proteintransferase (FPTase), in a dose
      dependent manner in vitro (IC50 value was calculated as 20 microM). It was also
      found to exhibit an inhibition upon the proliferation of cultured human tumor
      cells, i.e., A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma),
      XF498 (central nerve system) and HCT-15 (colon), in vitro.

PMID- 11458456
TI  - Inhibitory effects of maesanin and analogs on arachidonic acid metabolizing
      enzymes.
AB  - The substituted 1,4-benzoquinone, maesanin (1), is a potent 5-lipoxygenase (5-LO)
      inhibitor present in the fruit of Maesa lanceolata Forssk. Thirteen natural,
      synthetic, semisynthetic, and microbially transformed analogs of 1 were tested
      for their in vitro inhibition of 5-lipoxygenase (5-LO) and cyclooxygenase-1 (COX
      1). Maesanin was the most active 5-LO inhibitor. All other analogs were inactive
      or less active than the natural products as 5-LO inhibitors. None of the tested
      compounds was strongly active in the COX-1 inhibition assay.

PMID- 11458457
TI  - Inhibition of prostaglandin E2 production by platycodin D isolated from the root
      of Platycodon grandiflorum.
AB  - Platycodin D, isolated from the root of Platycodon grandiflorum A. DC.
      (Campanulaceae) suppressed prostaglandin E2 production at 10 and 30 microM in rat
      peritoneal macrophages stimulated by the protein kinase C activator 12-O
      tetradecanoylphorbol 13-acetate (TPA). Platycodin D3 and oleanolic acid showed no
      effect at these concentrations. Western blot analysis revealed that the induction
      of COX-2 protein by TPA was inhibited by platycodin D in parallel with the
      inhibition of prostaglandin E2 production. Platycodin D showed no direct effect
      on COX-1 and COX-2 activities. TPA-induced release of [3H]arachidonic acid from
      pre-labeled macrophages was also not inhibited by platycodin D.

PMID- 11458458
TI  - Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse
      macrophages by hpyericin, an active component of Hypericum perforatum.
AB  - Hypericin, an active component of Hypericum perforatum, was evaluated for the
      regulation of interleukin-12 (IL-12) production in mouse macrophages. Hypericin
      significantly inhibited IL-12 production in lipopolysaccharide-activated
      macrophages in a dose-dependent manner (IC50 = 1.45 micrograms/ml). Furthermore,
      hypericin potently inhibited the activation of IL-12 gene promoter, suggesting
      that hypericin negatively regulated IL-12 production at the transcription level.
      These results may explain some known biological activities of hypericin including
      its anti-rheumatic effect.

PMID- 11458459
TI  - Antioxidant activity of leaves of Salvia species in enzyme-dependent and enzyme
      independent systems of lipid peroxidation and their phenolic constituents.
AB  - The protective effects of eleven Salvia species native to Europe against enzyme
      dependent and enzyme-independent lipid peroxidation were evaluated. The 50%
      aqueous methanolic extracts of the leaves of all tested plants were found to be
      more effective than the positive control alpha-tocopherol acid succinate. The
      extracts of S. candelabrum, S. ringens, S. tomentosa, S. nemorosa, and S.
      glutinosa displayed considerable concentration-dependent antioxidative effects
      that were comparable to those of the medicinal and aromatic plant S. officinalis.
      The concentrations of flavonoids, hydroxycinnamic acids and total phenolic
      compounds in each extract were quantified with the aim of clarifying the
      connection between activity and chemical composition.

PMID- 11458460
TI  - Na+,K(+)-ATPase inhibiting activity of cardiac glycosides from Erysimum
      cheiranthoides.
AB  - We previously reported the isolation of eleven new cardiac glycosides called
      cheiranthosides I-XI together with two known ones (olitoriside and erysimoside)
      from the seeds of Erysimum cheiranthoides L. The glycosides were evaluated for
      their inhibitory activity against Na+,K(+)-ATPase by comparing with typical
      cardiac glycosides. Two of them, cheiranthoside III and VIII, showed high
      inhibiting activity which was equivalent to that of digitoxin. Cheiranthoside XI
      containing a rhamnopyranosyl digitoxopyranosyl moiety and a carboxyl group showed
      the lowest activity which was similar to that of the inactive aglycone,
      strophanthidin. Some characteristics in the structure-activity relationship are
      also discussed.

PMID- 11458461
TI  - 1-O-galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl-beta-D-glucose, a new
      hepatoprotective constituent from Combretum quadrangulare.
AB  - A new gallic acid derivative, 1-O-galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl
      beta-D-glucose (1) has been isolated from an H2O-fraction of MeOH extract of
      Combretum quadrangulare seeds. Compound 1 exhibited potent hepatoprotective
      activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse
      hepatocytes with an IC50 of 3.3 microM.

PMID- 11458462
TI  - SC-1, an antimycotic spirostan saponin from Solanum chrysotrichum.
AB  - A new antimycotic steroidal saponin named SC-1 has been isolated from the leaves
      of Solanum chrysotrichum by bioassay-guided fractionation. The structure of SC-1
      was characterized as 3-O-[beta-quinovopyranosyl(1-->6)-beta-glucopyranosyl(1-->6)
      beta- glucopyranosyl]chlorogenin on the basis of spectral analyses and chemical
      evidence.

PMID- 11458463
TI  - Evidence for paclitaxel from three new endophytic fungi of Himalayan yew of
      Nepal.
AB  - Taxus wallichiana, collected from the Himalayan region of Nepal, yielded, among
      others, three different endophytic fungi including Sporormia minima,
      Trichothecium sp., and an unidentified dimorphic fungus. Each was shown to
      produce paclitaxel in a culture medium. Each of these fungi represents a new
      report as a paclitaxel producer. The production of paclitaxel was confirmed by an
      immunoassay that utilized monoclonal antibodies, TLC chromatography as well as
      high performance liquid chromatography combined with on-line mass spectrometry.

PMID- 11458464
TI  - Rapid micro-assay of camptothecin in Camptotheca acuminata.
AB  - A micro-assay has been developed to extract and rapidly quantify the anticancer
      alkaloid, camptothecin (CPT), from two leaf disks of Camptotheca acuminata
      Decaisne (Nyssaceae). This assay utilizes thin-layer chromatography in
      conjunction with fluorescence imaging to obtain reproducible measurements in the
      nanogram range. A large number of trees can be screened using this procedure to
      identify high producers of CPT in a relatively short period of time.

PMID- 11458465
TI  - Differentiation of Lycium barbarum from its related Lycium species using random
      amplified polymorphic DNA.
AB  - The RAPD (random amplified polymorphic DNA) technique was applied for the first
      time to distinguish Lycium barbarum from other closely related species of the
      same genus. In this study, eight samples were collected, including five species,
      two varieties and one cultivated variety. A total of fifty arbitrary primers were
      used in the RAPD analysis. Distinctive DNA fingerprints corresponding to
      different Lycium species were successfully obtained from ten primers. Similarity
      index (S.I.) analysis revealed that the values are higher between intraspecies
      than interspecies. These results confirmed that the RAPD technique can be
      employed for distinguishing closely related species of Lycium.

PMID- 11458466
TI  - Characters of nrDNA ITS region sequences of fruits of Alpinia galanga and their
      adulterants.
AB  - The fruits of Alpinia galanga (L.) Sw. are used as a traditional Chinese
      medicine; but the dry fruits of A. conchigera, A. suishaensis, A. maclurei and A.
      polyantha are also used as the medicine in local areas. Because dry fruits of
      these related plants are similar to those of Alpinia galanga (L.) Sw. in odor,
      morphological characters and chemical components, and even anatomical characters,
      it is difficult to identify the medicine. Nuclear ribosomal DNA internal
      transcribed spacer (ITS) regions of the five taxa were directly sequenced using
      an automated sequencer. Sequence analysis showed that the ITS 1 ranges from 177
      to 178 base pairs (bp), and the ITS 2 from 225 to 234 bp. The size of the 5.8S
      coding region is 164 bp for all species. Also, the pairwise sequence divergence
      is higher and some molecular markers were determined. According to these
      molecular markers, Alpinia galanga (L.) Sw. and the related species can easily be
      distinguished from each other. Therefore, evidence from nrDNA ITS sequence
      variation can identify the medicine at the DNA level.

PMID- 11458467
TI  - Molecular markers as a tool to verify sexual and apomictic off-spring of
      intraspecific crosses in Hypericum perforatum.
AB  - The aim of this project was to establish RAPD markers to determine the percentage
      of sexual off-spring of the facultative apomictic plant species H. perforatum. We
      did reciprocal crosses between four different accessions (A x B, B x A, C x D, D
      x C) by mechanical emasculation and hand pollination. Genomic DNA of the parents
      and the off-spring was isolated and PCR conditions were optimized in order to
      obtain reproducible bands with RAPD markers. Of the 260 screened RAPD primers 127
      revealed polymorphism between the parental lines of A and B, whereas 53 revealed
      no amplification products. Each progeny was tested for the presence of paternal
      bands with three primers. We found no sexual off-spring among the 22 progenies of
      A x B, the nine progenies of B x A and the ten progenies of D x C. However, we
      detected six sexual off-spring among the 45 progenies of C x D. We have proved
      that RAPD markers can be used to distinguish between sexual and apomictic off
      spring in H. perforatum and that sexual off-spring can be obtained from
      intraspecific crosses. The percentage of sexual progeny might depend on the
      genotype of the parental lines.

PMID- 11458468
TI  - Authentication of Chinese crude drug, Gecko, by allele-specific diagnostic PCR.
AB  - Based on the sequences of the mitochondrial 12S rRNA gene fragment of 17 samples
      from Gekkonidae, Salamandridae, Agamidae and Hynobiidae, respectively, a pair of
      allele-specific primers was designed for differentiating the Chinese medicinal
      material Gecko from its adulterants by PCR. The results of amplification with the
      primers indicate that amplicons from the templates of Gekko gecko were clearly
      revealed by agarose gel electrophoresis, whereas no evident amplicons were found
      from other species. The primers were employed to identify crude drug samples from
      different sources. Among a total of 9 samples, 3 were diagnosed as genuine Gecko.
      This result is consistent with morphological identification and DNA sequence
      analyses.

PMID- 11458469
TI  - Phenolic constituents of Ononis vaginalis roots.
AB  - The ether soluble fraction of the roots of Ononis vaginalis Vahl. Symb. afforded
      three new compounds: 3-hydroxy-4,9-dimethoxycoumestan, maginaldehyde [2-(4
      hydroxy-2-methoxyphenyl)-5,6-dimethoxy-3-benzofuran-carboxaldehyde] and 5,7,4'
      trihydroxy-4-styrylcoumarin. In addition, four known pterocarpans; 3,4,9
      trimethoxypterocarpan, maackiain, medicarpin and trifolirhizin were also
      isolated. The styrylcoumarin derivative showed significant antiviral activity
      against Herpes simplex type 1 and weak cytotoxicity.

PMID- 11458470
TI  - Defined contribution programs: how physicians and medical groups can prepare now
      for their impact.
AB  - Facing continued premium increases and escalating employee dissatisfaction,
      employers and other purchasers are implementing defined contribution programs for
      health care benefits. These programs depart from traditional health benefits by
      offering employees more flexibility and using Internet services to streamline
      administrative processes. This article gives an overview of these defined
      contribution programs and suggests steps medical practices can take to prepare
      for them. While these programs remain largely untested, they could present
      physicians with opportunities to improve financial performance and enhance
      patient satisfaction.

PMID- 11458471
TI  - Choosing the best Internet service provider for your medical group practice.
AB  - The process of choosing an Internet service provider for your medical practice
      involves a needs assessment, a close comparison of vendor capabilities and access
      technologies, and an evaluation of security protocols and costs.

PMID- 11458472
TI  - In the palm of your hand.
AB  - The explosive growth of handheld personal digital assistants (PDAs) in health
      care has been nothing short of amazing. What applications--business and clinical-
      do these devices have in medicine, and what is their potential? PDAs are simple
      and intuitive; their applications require minimal interaction time, so they have
      minimal impact on work flow: the investment is small; and the lightweight form is
      relatively nonintrusive during a patient encounter. The devices are being used to
      capture charges for medical services at the point of care. Encounter capture,
      online prescription writing and other applications will soon come on the scene.
      This article discusses current and possible future uses for PDAs in health care,
      interfaces with other technologies and security concerns.

PMID- 11458473
TI  - Kokomo family care: automating the clinical practice.
AB  - A 14-physician family practice automated its prescription process, telephone
      messaging and laboratory test reporting to streamline its operations and contain
      costs.

PMID- 11458474
TI  - Risks--listen and don't mislead.

PMID- 11458475
TI  - Outreach clinics in the new NHS: not yet the end of outpatients.

PMID- 11458476
TI  - Quality, general practice, and the NHS plan.

PMID- 11458477
TI  - A national evaluation of specialists' clinics in primary care settings.
AB  - BACKGROUND: Encouraged by the increased purchasing power of general practitioners
      (GPs), specialist-run clinics in general practice and community health care
      settings (known as specialist outreach clinics) have increased rapidly across
      England. The activities of local commissioning schemes within primary care groups
      are likely to accelerate this trend. AIM: To evaluate the costs, processes, and
      benefits of specialists' outreach clinics held in GPs' surgeries, compared with
      hospital outpatient clinics. DESIGN OF STUDY: A case-referent (comparative) study
      comparing the characteristics of outreach clinics (cases) with matched outpatient
      control clinics. SETTING: Thirty-eight outreach clinics, compared with 38 matched
      outpatient clinics as controls, covering 14 hospital trust areas across England.
      METHOD: Self-administered questionnaires were given to patients in both clinic
      settings. These covered processes, satisfaction, personal costs, and health
      status, with postal follow-up at six months to assess health outcomes. Self
      administered questionnaires were also given to the specialists and GPs whose
      clinics were included in the study (individual patient clinical sheet and an
      attitude questionnaire), practice managers, and trust accountants (process and
      costs questionnaire). Evaluation of the costs, processes, and benefits of
      specialist outreach clinics versus hospital outpatient clinics was carried out by
      comparing questionnaire responses. RESULTS: In comparison with outpatients,
      outreach clinic patients spent less time on the waiting lists for appointments to
      see the specialist, they had shorter waiting times in clinics, fewer follow-up
      appointments, and were more likely to be completely discharged after the sampled
      attendance. Outreach patients were more satisfied than outpatients with the range
      of clinic process items asked about. Most doctors felt that the outreach clinic
      was 'worthwhile'. While patients' personal costs were lower in outreach than in
      outpatients clinics, NHS costs were more expensive per patient in outreach. The
      benefits of outreach clinics on patients' health status at six months' follow-up
      were relatively small. CONCLUSIONS: Outreach clinics are a means of improving
      access to specialist services for patients, in addition to improving the
      efficiency and quality of health care. Most results were similar across
      specialties and areas. The benefits of the outreach service need to be weighed
      against their substantially higher NHS costs, in comparison with outpatients
      clinics. Outreach clinics are unlikely to be financially justifiable for NHS
      funding given that the impact on patients' health status was small.

PMID- 11458478
TI  - General practitioners' perceptions of the appropriateness and inappropriateness
      of out-of-hours calls.
AB  - BACKGROUND: The number of out-of-hours calls to general practitioners (GPs) has
      increased steadily during the past 20 years. The proportion of inappropriate
      calls are reportedly increasing but we know very little about how GPs judge a
      call to be appropriate or inappropriate. AIM: To determine the factors that
      influence GPs' perceptions of the appropriateness or inappropriateness of out-of
      hours calls. DESIGN OF STUDY: Postal questionnaire survey. SETTING: GP members of
      the Wessex Primary Care Research Network (WReN) and the Northern Primary Care
      Research Network (NoReN). METHOD: General Practitioners were asked to write down
      what they meant by an 'appropriate' and 'inappropriate' out-of-hours call. The
      free text was subjected to content analysis. RESULTS: Detailed responses were
      received from 146 (73%) GPs. General practitioners appear to have a well
      developed classification of the appropriateness of out-of-hours calls. Factors
      that make calls appropriate include not only the nature of patients' symptoms and
      illness but also non-medical factors such as patients' compliance and politeness.
      CONCLUSION: The inclusion by GPs of non-medical factors in their
      conceptualisation of the appropriateness of out-of-hours calls may contribute to
      patients' confusion about what is and is not appropriate and also to the apparent
      failure of patient education initiatives designed to decrease inappropriate
      demand.

PMID- 11458479
TI  - Patients' responses to risk information about the benefits of treating
      hypertension.
AB  - BACKGROUND: The medical profession is often presented with information on the
      value of treatment in terms of likely risk reduction. If this same information
      was presented to patients--so enabling them to give proper informed consent-
      would this affect their decision to be treated? AIM: To examine patients' choice
      about treatment in response to different forms of risk presentation. DESIGN OF
      STUDY: Postal questionnaire study. SETTING: The questionnaire was sent to 102
      hypertensive patients and 207 matched non-hypertensive patients aged between 35
      and 65 years in a UK general practice. METHODS: Patients were asked the
      likelihood, on a four-point scale, of their accepting treatment for a chronic
      condition (mild hypertension) on the basis of relative risk reduction, absolute
      risk reduction, number needed to treat, and personal probability of benefit.
      RESULTS: An 89% response rate was obtained. Of these, 92% would accept treatment
      using a relative risk reduction model, 75% would accept treatment using an
      absolute risk reduction model, 68% would accept treatment using a number needed
      to treat model, and 44% would accept treatment with a personal probability of
      benefit model. CONCLUSION: Many patients may prefer not to take treatment for
      mild hypertension if the risks were fully explained. However, given that the form
      of the explanation has a strong influence on the patient's decision, it is not
      clear how decision-making can be fully shared nor what should constitute informed
      consent to treatment in this situation.

PMID- 11458480
TI  - Managing patient demand: a qualitative study of appointment making in general
      practice.
AB  - BACKGROUND: Managing patients' requests for appointments is an important general
      practice activity. No previous research has systematically observed how patients
      and receptionists negotiate appointments. AIM: To observe appointment making and
      investigate patients' and professionals' experiences of appointment negotiations.
      DESIGN OF STUDY: A qualitative study using participant observation. SETTING:
      Three general practices on Tyneside; a single-handed practice, a practice
      comprising three doctors, and a seven-doctor practice. METHOD: Participant
      observation sessions, consisting of 35 activity recordings and 34 periods of
      observation and 38 patient and 15 professional interviews, were set up. Seven
      groups of patients were selected for interview. These included patients attending
      an 'open access' surgery, patients who complained about making an appointment,
      and patients who complimented the receptionists. RESULTS: Appointment making is a
      complex social process. Outcomes are dependent on the process of negotiation and
      factors, such as patients' expectations and appointment availability.
      Receptionists felt that patients in employment, patients allocated to the
      practice by the Health Authority, and patients who did not comply with practice
      appointment rules were most demanding. Appointment requests are legitimised by
      receptionists enforcing practice rules and requesting clinical information.
      Patients volunteer information to provide evidence that their complaint is
      appropriate and employ strategies, such as persistence, assertiveness, and
      threats, to try and persuade receptionists to grant appointments. CONCLUSION:
      Appointment making is a complex social process where outcomes are negotiated.
      Receptionists have an important role in managing patient demand. Practices should
      be explicit about how appointments are allocated, including publishing practice
      criteria.

PMID- 11458481
TI  - Rural general practitioners' experience of the provision of out-of-hours care: a
      qualitative study.
AB  - BACKGROUND: Published research into the provision and utilisation of out-of-hours
      services shows long-term trends towards decreasing personal commitment among
      general practitioners (GPs). However, the on-call commitments of rural GPs remain
      especially onerous. There has been little research relating to either rural out
      of-hours services or the implications of such services for the families of the
      providers. AIM: To explore and describe how rural GPs in Ireland perceive and
      experience out-of-hours care provision. DESIGN OF STUDY: A qualitative study was
      conducted with 10 rural GPs and their spouses in their homes or practices using
      one-to-one in-depth interviews. SETTING: Ten general practices in rural Ireland.
      METHOD: The interviews were guided by an interview schedule that was based on
      pertinent themes that had emerged from previous relevant literature. The
      interviews were audiotaped, transcribed, and analysed for themes and issues.
      RESULTS: Results indicated that rural GPs experience a wide variety of
      satisfactions from work related to the provision of out-of-hours care. However,
      the large proportion of time committed to out-of-hours care greatly infringes on
      their social and family life. The key stressors identified related to
      organisational system difficulties, especially with regard to locum cover, and
      unrealistic patient expectations. The stressors were mainly expressed as lack of
      time off, restrictions on family life, and interruptions. CONCLUSION: System
      difficulties, such as difficulty with obtaining locums and rota extension, need
      to be addressed at an organisational level. Patient expectations of the role of
      the rural GP have significant implications for practitioners and their families.

PMID- 11458482
TI  - Individualised multifactorial lifestyle intervention trial for high-risk
      cardiovascular patients in primary care.
AB  - BACKGROUND: The multiprofessional teams in Finnish health centres are well placed
      to carry out interventions aimed at the prevention of cardiovascular diseases.
      AIM: To evaluate the effectiveness of an individually tailored multifactorial
      lifestyle intervention in primary care for individuals at high risk for
      cardiovascular disease. DESIGN OF STUDY: A randomised controlled trial was
      conducted over 24 months with interim assessments at six and 12 months. SETTING:
      A health centre in Finland with a patient population of 11,000. METHOD: One
      hundred and fifty adults aged 18 to 65 years old with existing cardiovascular
      disease or multiple risk factors were randomised to active multiprofessional risk
      factor intervention or to standard care. The main outcome measure was a change in
      cardiovascular risk-factor score. Secondary outcomes were changes in blood
      pressure, weight, body-mass index, serum cholesterol, blood glucose, smoking
      cessation, and exercise habits. RESULTS: The cardiovascular risk score decreased
      by 28% in the intervention group (23% in the control group), body weight
      decreased by 3.7% (2%) and total cholesterol decreased by 10.8% (6.5%), while
      time engaged in exercise increased by 39% (43%). Differences were not
      significant. CONCLUSIONS: Cardiovascular risk levels of high-risk individuals
      decreased in both intervention and control groups. Primary care prevention should
      be targeted to high-risk persons. Long-term follow-up studies are needed.

PMID- 11458483
TI  - The impact of patient suicide on rural general practitioners.
AB  - This survey of 152 rural general practitioners (GPs) studied the impact of
      patient suicide on their professional and personal lives. The response rate was
      79%, with the average GP encountering a patient suicide every three years. The
      reactions of GPs to patient suicide were similar to those expressed by other
      health care workers. Factors that lessened the effects of patient suicide were
      identified and most GPs indicated their preference for a support system to be
      established to facilitate GPs in dealing with the aftermath of practice suicide.

PMID- 11458484
TI  - Outbreak of tuberculosis linked to a source case imprisoned during treatment.
      Should the courts tell GPs about prison sentences and should GPs tell prison
      doctors about medical diagnoses?

PMID- 11458485
TI  - New paradigms for quality in primary care.

PMID- 11458486
TI  - Carpal tunnel syndrome: modern diagnostic and management techniques.
AB  - Carpal tunnel syndrome is a common disorder characterised by the classical
      symptoms of numbness and paraesthesiae along the distribution of the median
      nerve. Thenar muscle weakness is a late manifestation of advanced disease.
      Tinel's and Phalen's signs are helpful in suggesting the diagnosis. The symptoms
      and signs arise from entrapment of the median nerve. Electrophysiological tests
      are helpful in confirming the diagnosis and magnetic resonance imaging may be
      used in the diagnosis of atypical cases. Ergonomic manoeuvers and steroid
      injections may alleviate symptoms in mild cases. Surgery is reserved for severe
      cases and those who do not respond to conservative therapy. Open carpal tunnel
      release is the classical surgery with usually excellent results. Endoscopic
      carpal tunnel release surgery was introduced to decrease the morbidity of open
      surgery. This latter technique also has its complications and is still being
      refined.

PMID- 11458487
TI  - Children and clinical trials.

PMID- 11458488
TI  - Identifying alcohol dependency.

PMID- 11458489
TI  - Cognitive behaviour therapy and chronic fatigue syndrome.

PMID- 11458490
TI  - Chronic fatigue in general practice.

PMID- 11458491
TI  - Rapid referral in the electrical cardioversion of atrial fibrillation.

PMID- 11458492
TI  - School students and the clinical arena.

PMID- 11458493
TI  - The general practitioner's expectations of a general physician/rheumatologist.

PMID- 11458494
TI  - What can general practice learn from complementary medicine?

PMID- 11458495
TI  - Female genital mutilation.

PMID- 11458496
TI  - Limited telomere shortening in hematopoietic stem cells after transplantation.
AB  - The number of cell divisions in hematopoietic stem cells (HSCs) following
      transplantation of bone marrow or mobilized peripheral blood into myelo-ablated
      recipients is unknown. This number is expected to depend primarily on the number
      of transplanted stem cells, assuming that stem cells do not differ in engraftment
      potential and other functional properties. In a previous study, we found that the
      telomere length in circulating granulocytes in normal individuals shows a
      biphasic decline with age, most likely reflecting age-related changes in the
      turnover of HSCs. In order to study HSCs' proliferation kinetics following stem
      cells transplantation, we analyzed the telomere length in donor-derived nucleated
      blood cells in four HLA-matched bone marrow transplant recipients relative to
      comparable cells from the sibling donors. In each case, the telomeres in
      granulocytes were shorter in the recipient than in the donor. This difference was
      established in the first year post transplantation and did not change after that.
      The telomere length in naive and memory T cells showed marked differences after
      transplantation, complicating the interpretation of telomere length data using
      unseparated nucleated blood cells. Interestingly, the telomere length in naive T
      cells that were first observed six months post transplantation was very similar
      in donor and recipient pairs. Our observations are compatible with a limited
      number of additional cell divisions in stem cell populations after bone marrow
      transplantations and support the idea that different populations of stem cells
      contribute to short-term myeloid and long-term lympho myeloid hematopoiesis.

PMID- 11458497
TI  - Role of the microenvironment of the embryonic aorta-gonad-mesonephros region in
      hematopoiesis.
AB  - Although various cytokines, growth factors, and chemokines are known to regulate
      hematopoiesis, expansion of hematopoietic stem cells (HSCs) in vitro with the use
      of such agents has proved problematic. Stromal cells are major components of the
      microenvironment that surrounds hematopoietic cells and are thought to play an
      important role in hematopoiesis in vivo. Co-culture of HSCs with stromal cells
      promotes hematopoiesis and self-renewal of HSCs. Definitive hematopoietic cells
      first appear during mammalian embryonic development in the aorta-gonad
      mesonephros (AGM) region, and it is therefore thought that the microenvironment
      of this region plays an important role in HSC ontogeny. We have adopted two
      approaches to studying the contribution of the AGM microenvironment to
      hematopoiesis. In the first approach, we have developed an in vitro culture
      system for mouse AGM explants. Hematopoiesis is enhanced in such cultures by the
      presence of the combination of stem cell factor (SCF), basic fibroblast growth
      factor, leukemia inhibitory factor, and oncostatin M (SFLO culture). However,
      transplantation assays revealed that HSCs capable of long-term reconstitution of
      the hematopoietic compartment of irradiated mice (LTR-HSCs) do not expand in AGM
      SFLO cultures; rather, these cultures appear to provide a favorable
      microenvironment for hematogenic angioblasts that are precursors of both
      endothelial and hematopoietic cells. In our second approach, we have established
      various stromal cell lines from the mouse AGM region. The AGM-S3 cell line
      supports human and mouse primitive hematopoietic cells as well as mouse LTR-HSCs.
      Maintenance of LTR-HSCs is mediated by a mechanism other than SCF signaling
      through its receptor (c-Kit). These two in vitro approaches should prove useful
      for further elucidation of the mechanisms that underlie hematopoiesis and HSC
      self-renewal.

PMID- 11458498
TI  - Chemokine regulation of hematopoiesis and the involvement of pertussis toxin
      sensitive G alpha i proteins.
AB  - Chemokines have been implicated in regulation of various aspects of
      hematopoiesis, including negative regulation of the proliferation of immature
      subsets of myeloid progenitor cells (MPCs), chemotaxis of MPCs, and survival
      enhancement of MPCs after delayed growth factor addition. Since chemokine
      receptors are seven-transmembrane-spanning G-protein-linked receptors and the
      chemotactic effect in vitro of the CXC chemokine SDF-1 is pertussis toxin (PT)
      sensitive, implying the involvement of G alpha i proteins as mediators of SDF-1
      induced chemotaxis, we evaluated the effects of PT on other chemokine actions
      influencing MPCs. While the in vitro survival-enhancing effects of SDF-1 on GM
      CSF and steel factor-dependent mouse bone marrow granulocyte macrophage
      progenitors (CFU-GM) were pertussis toxin-sensitive, the suppressive effects of
      the CC chemokine MIP-1 alpha and the CXC chemokine IL-8 on colony formation by GM
      CSF and steel factor-sensitive CFU-GM were insensitive to pertussis toxin. These
      results suggest that not all chemokine-mediated effects on MPCs are necessarily
      mediated through pertussis toxin-sensitive G alpha i proteins.

PMID- 11458499
TI  - Pathways in cytokine regulation of hematopoiesis.

PMID- 11458500
TI  - Hematopoietic growth factor mimetics.
AB  - Hematopoietic growth factors are glycoproteins of 15-70 kDa. Although much
      clinical success has been obtained using recombinant proteins produced in
      mammalian cell lines and in microbial fermentation processes, the full-length
      polypeptides necessarily are expensive to produce, require parenteral
      administration, and in some cases have provoked detrimental immune responses.
      With the availability of high throughput biological function and receptor binding
      assays it has become possible to screen millions, if not billions, of randomly
      produced organic compounds and relatively short peptides to identify lead
      compounds for the development of small molecular mimetics of hematopoietic growth
      factors. Herein the strategies used to screen libraries of small molecules and
      peptides and the successes in finding mimetics and antagonists for/to
      erythropoietin, granulocyte colony-stimulating factor, and thrombopoietin are
      reviewed. Finally, the structural study of mimetic-receptor complexes has
      provided us with many molecular details of growth factor-induced receptor
      activation and is likely to yield new insights into the molecular basis of
      hematopoietic signal transduction.

PMID- 11458501
TI  - CD34 expression by murine hematopoietic stem cells. Developmental changes and
      kinetic alterations.
AB  - For more than a decade it was believed that hematopoietic stem cells express
      CD34. However, this dogma was recently challenged by the observation that stem
      cells of normal adult mice are CD34-. In order to clarify the controversy, we
      carried out systematic examination of stem cells by using C57BL/6 mice that are
      congenic for Ly-5. As reported previously, stem cells in the normal adult mice
      were CD34-. However, stem cells stimulated in vivo by 5-fluorouracil injection or
      in vitro by a combination of interleukin-11 and steel factor were CD34+. The
      activated CD34+ stem cells reverted to CD34- when the recipients' marrow achieved
      steady state. The majority of G-CSF-mobilized stem cells also were CD34+ and
      reverted to CD34- under steady-state conditions. Most recently, we examined the
      developmental changes of stem cell CD34 expression. In order to gain information
      on the total population of stem cells we prepared CD34+ and CD34- populations of
      mononuclear cells without prior enrichment and studied their engrafting
      potentials. All stem cells from perinatal to 5-week-old mice were CD34+. In 7
      week-old mice CD34- stem cells began to emerge, and the majority of the stem
      cells were CD34- in the 10- and 20-week-old mice. An estimated 20% of the adult
      stem cells expressed CD34. These observations provide insight into the current
      controversy regarding CD34 expression by adult hematopoietic stem cells.

PMID- 11458502
TI  - A model for the detection of clonality in marked hematopoietic stem cells.
AB  - The semirandom location of retroviral integration in the target cell genome
      introduces a marker in the form of a fusion sequence composed of a genomic and a
      proviral part that is unique for each transduced cell and its clonal progeny.
      High-sensitivity detection of these fusion sequences would allow the tracking of
      clonal contributions of individual, marked hematopoietic progenitor, and stem
      cells in vivo. Clone detection by Southern blot has helped to analyze models of
      oligoclonal repopulation but is limited in sensitivity and specificity. Inverse
      PCR (Nolta et al., Proc. Natl. Acad. Sci. USA 93: 2414-2419) can demonstrate the
      clonal identity by sequencing but does not permit simultaneous detection of
      multiple clones. In an efficiently transduced rhesus macaque model (Tisdale et
      al., Blood 92: 2681-2687; Wu et al., Mol. Ther. 1: 285-293) Kim et al. (Blood 96:
      1-8) have identified more than 40 insertion sequences from marrow CFU by inverse
      PCR. However, no previous study has been able to directly analyze the number of
      clones active in vivo. Here we demonstrate that the application of a recently
      developed PCR technology allows the simultaneous visualization of multiple
      integration sites from small clonal contributions to hematopoietic cells. By
      combining solid-phase primer extension with ligation-mediated PCR, direct genomic
      sequencing of retroviral integration sites was obtained in murine bone marrow
      samples. Further development of this technology will allow analysis of the clonal
      composition of marked hematopoiesis in small and large animals as well as in
      human gene transfer.

PMID- 11458503
TI  - Observations of residual differentiation potential during lineage commitment.
AB  - We have recently described a subset of the multipotent progenitor pool that
      contains a common lymphoid progenitor. This subset of cells is lineage negative
      and expresses c-kit and Sca-1, but lacks expression of Thy 1.1 (Thyneg). Based on
      the observation that lethally irradiated mice transplanted with these cells die
      from anemia unless supported with competitor marrow, we hypothesized that these
      progenitors lacked erythroid potential. We analyzed the erythroid potential of
      these cells by transplanting them into mice allelic at the hemoglobin locus and
      compared their erythroid potential with the Thy-1.1low (Thylow) subset that
      contains hematopoietic stem cells. We also performed CFU-C assays in
      methylcellulose containing recombinant cytokines and determined erythroid
      contribution to colonies using in situ benzidine staining. Donor-derived
      hemoglobin was observed following transplant of Thyneg cells, even though 19 of
      20 of these animals died from anemia. In contrast, recipients of Thylow cells
      showed complete donor-derived engraftment 30 days following transplant. While
      approximately 60% of day 4 colonies derived from Thyneg cells expressed
      hemoglobin, by day 11 less than 5% were hemoglobinized. In contrast, greater than
      70% of the Thylow subset contained hemoglobinized cells at the end of the
      observation period. A similar transient appearance of myeloid progeny was also
      observed in colonies derived from c-kitlow Thyneg lymphoid progenitor cells. We
      conclude that these studies demonstrate commitment to the lymphoid lineage at the
      Thylow-to-Thyneg interface, and that the loss of erythroid and myeloid potential
      is gradual rather than abrupt. Hemoglobinized colonies may be undergoing
      apoptosis because of down-regulation of GATA-1 or because of a death signal from
      surrounding nonerythrocytic cells.

PMID- 11458504
TI  - Dendritic cell development from common myeloid progenitors.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells which both
      initiate adaptive immune responses and control tolerance to self-antigens. It has
      been suggested that these different effects on responder cells depend on subsets
      of DCs arising from either myeloid or lymphoid hematopoietic origins. In this
      model, CD8 alpha+ Mac-1- DCs are supposed to be of lymphoid while CD8 alpha- Mac
      1+ DCs are supposed to be of myeloid origin. Here we summarize our findings that
      both CD8 alpha+ and CD8 alpha- DCs can arise from clonogenic common myeloid
      progenitors (CMPs) in both thymus and spleen. Therefore CD8 alpha expression DCs
      does not indicate a lymphoid origin and differences among CD8 alpha+ and CD8
      alpha- DCs might rather reflect maturation status than ontogeny. On the basis of
      transplantation studies, it seems likely that most of the DCs in secondary
      lymphoid organs and a substantial fraction of thymic DCs are myeloid-derived.

PMID- 11458505
TI  - The monoclonal antibody W7C5 defines a novel surface antigen on hematopoietic
      stem cells.
AB  - We recently raised a monoclonal antibody, termed W7C5, against a surface antigen
      that is expressed at low levels on bone marrow and peripheral blood CD34+
      stem/progenitor cells but at high levels on fetal liver CD34+ cells. A reasonable
      staining intensity was achieved using magnetofluorescent liposome conjugates to
      analyze expression of W7C5 antigen on CD34+CD38- bone marrow (BM) cells. Flow
      cytometric analyses revealed that W7C5 detects about 50% of immature CD34+CD38-
      BM cells that coexpressed the differentiation antigens CD164, CD133, and CD172a
      (SIRP alpha). In addition, W7C5 also recognized a CD34- BM fraction. These cells
      were negative for CD117 and CD133, but expressed CD45 and moderate levels of
      CD164. Injection of selected CD34+W7C5+ and CD34-W7C5+ cells into 55-60-day-old
      fetal sheep resulted in an engraftment of both fractions. Partial amino acid
      sequence analysis of affinity-purified lysates of KU-812 cells revealed that W7C5
      detects a novel membrane protein. Together, W7C5 defines a novel molecule that is
      expressed on CD34+ as well as on CD34- stem cell subsets.

PMID- 11458506
TI  - Quantitative assessment of the stem cell self-renewal capacity.
AB  - Little is known about the manner in which hematopoietic stem cells (HSCs) self
      renew. To address this issue, we used a serum-free single-cell culture, followed
      by transplantation of cultured cells into lethally irradiated mice. CD34-negative
      or low, c-Kit-positive, Sca-1-positive, lineage marker-negative (CD34-KSL) cells
      are highly enriched for murine bone marrow HSCs. Successful long-term
      reconstitution with a single CD34-KSL cell enabled us to study in vitro self
      renewal of HSC at clonal level. Using this clonal cell transplantation system, we
      examined the effect of various cytokines on CD34-KSL cells. Among the cytokines
      examined, stem cell factor (SCF) and thrombopoietin (TPO) were minimum cytokines
      to induce cell division of CD34-KSL cells most efficiently. Similarly,
      multilineage repopulating activity was detected in the cells derived from a
      significant portion of single cells after culture in the presence of TPO and SCF.
      However, SCF + IL-3, SCF + IL-6, or SCF + IL-11 + FL appeared to be less
      effective for self-renewal of HSCs. The activity of HSCs as indicated by
      repopulation unit (RU) remaining after culture with SCF and TPO was not so
      different from that of freshly isolated HSCs. However, there was a substantial
      loss of HSC number in these cultured cells. Taken together, this study provides
      definitive proof that one HSC can generate at least one HSC in vitro.

PMID- 11458507
TI  - In vivo dynamics of human stem cell repopulation in NOD/SCID mice.
AB  - Primitive human hematopoietic cells can be assayed on the basis of their ability
      to repopulate immune-deficient NOD/SCID mice and have been termed SCID
      repopulating cells (SRCs). The in vivo biological fate of individual SRCs can be
      tracked by following the unique retroviral insertion site in the progency of
      transduced SRCs. Distinct human SRCs were identified that differ in the
      proliferative and self-renewal capacity indicating that the primitive cell
      compartment is functionally heterogeneous.

PMID- 11458508
TI  - Phenotype and function of hematopoietic stem cells.
AB  - Using an in vivo selection technique, we can isolate individual cells that can
      repopulate the hematopoietic system of a lethally irradiated murine recipient.
      These cells rapidly acquire a CD34 phenotype in the animal. Progenitors in our
      long-term chimeras are of donor type. We also have evidence that transplantation
      of limiting numbers (as low as a single cell) that have this long-term
      repopulating ability (LTRA) can self-renew. This is demonstrated by serial
      transplantation of marrow from engrafted recipients 11 months post transplant
      into new hosts for four additional months.

PMID- 11458509
TI  - Mucin-like molecules as modulators of the survival and proliferation of primitive
      hematopoietic cells.
AB  - Current data suggest that interplay between two classes of molecules contributes
      to the regulation of hematopoiesis: hematopoietic growth factors, which regulate
      the survival, proliferation, and development of primitive hematopoietic cells and
      cell adhesion molecules (CAMs), which are responsible for the localization of
      hematopoiesis to the bone marrow (BM) and for mediating physical association
      between developing hematopoietic cells and marrow stromal tissue. A range of cell
      surface molecules representing several CAM superfamilies including integrins,
      selectins, the immunoglobulin gene superfamily and an emerging family of mucin
      like molecules (the sialomucins) are involved in supporting cell-cell and cell
      extracellular matrix (ECM) interactions between primitive hematopoietic cells and
      the stromal cell-mediated hematopoietic microenvironment (HM) of the bone marrow.
      There is abundant evidence in non-hematopoietic tissues that CAMs are signalling
      molecules which participate in a range of signal transduction events important
      not only for regulating cell adhesion and motility, but also for cell growth and
      survival. Although the signalling functions of CAMs have not been studied
      extensively in primitive hematopoietic progenitors (HPCs), extrapolation from
      burgeoning data in other systems is consistent with the hypothesis that
      hematopoiesis within the BM is regulated by interaction between signals generated
      locally by CAMs and those elicited by cytokines. Evidence in support of this
      notion was initially provided by studies on normal HPCs demonstrating cross-talk
      between members of the integrin superfamily and cytokine receptors. In this
      article we review recent reports that mucin-like molecules are also signalling
      molecules on primitive hematopoietic cells and that the signals they deliver
      potently inhibit hematopoiesis.

PMID- 11458510
TI  - Stem cell plasticity in muscle and bone marrow.
AB  - Recent discoveries have demonstrated the extraordinary plasticity of tissue
      derived stem cells, raising fundamental questions about cell lineage
      relationships and suggesting the potential for novel cell-based therapies. We
      have examined this phenomenon in a potential reciprocal relationship between stem
      cells derived from the skeletal muscle and from the bone marrow. We have
      discovered that cells derived from the skeletal muscle of adult mice contain a
      remarkable capacity for hematopoietic differentiation. Cells prepared from muscle
      by enzymatic digestion and 5 day in vitro culture were harvested and introduced
      into each of six lethally irradiated recipients together with distinguishable
      whole bone marrow cells. Six and twelve weeks later, all recipients showed high
      level engraftment of muscle-derived cells representing all major adult blood
      lineages. The mean total contribution of muscle cell progeny to peripheral blood
      was 56%, indicating that the cultured muscle cells generated approximately 10- to
      14-fold more hematopoietic activity than whole bone marrow. Although the identity
      of the muscle-derived hematopoietic stem cells is still unknown, they may be
      identical to muscle satellite cells, some of which lack myogenic regulators and
      could respond to hematopoietic signals. We have also found that stem cells in the
      bone marrow can contribute to cardiac muscle repair and neovascularization after
      ischemic injury. We transplanted highly purified bone marrow stem cells into
      lethally irradiated mice that subsequently were rendered ischemic by coronary
      artery occlusion and reperfusion. The engrafted stem cells or their progeny
      differentiated into cardiomyocytes and endothelial cells and contributed to the
      formation of functional tissue.

PMID- 11458511
TI  - Transplanted adult bone marrow cells repair myocardial infarcts in mice.
AB  - Occlusion of the anterior descending left coronary artery leads to ischemia,
      infarction, and loss of function in the left ventricle. We have studied the
      repair of infarcted myocardium in mice using highly enriched stem/progenitor
      cells from adult bone marrow. The left coronary artery was ligated and 5 hours
      later Lin- c-kit+ bone marrow cells obtained from transgenic male mice expressing
      enhanced green fluorescent protein (EGFP) were injected into the healthy
      myocardium adjacent to the site of the infarct. After 9 days the damaged hearts
      were examined for regenerating myocardium. A band of new myocardium was observed
      in 12 surviving mice. The developing myocytes were small and resembled fetal and
      neonatal myocytes. They were positive for EGFP, Y chromosome, and several myocyte
      specific proteins including cardiac myosin, and the transcription factors GATA-4,
      MEF2, and Csx/Nkx2.5. The cells were also positive for connexin 43, a gap
      junction/intercalated disc component indicating the onset of intercellular
      communication. Myocyte proliferation was demonstrated by incorporation of BrdU
      into the DNA of dividing cells and by the presence of the cell cycle-associated
      protein K167 in their nuclei. Neo-vascularization was also observed in
      regenerating myocardium. Endothelial and smooth muscle cells in developing
      capillaries and small arterioles were EGFP-positive. These cells were positive
      for Factor VIII and alpha smooth muscle actin, respectively. No myocardial
      regeneration was observed in damaged hearts transplanted with Lin- c-kit- bone
      marrow cells, which lack bone marrow-regenerating activity. Functional competence
      of the repaired left ventricle was improved for several hemodynamic parameters.
      These in vivo findings demonstrate the capacity of highly enriched Lin- c-kit+
      adult bone marrow cells to acutely regenerate functional myocardium within an
      infarcted region.

PMID- 11458512
TI  - Characterization of multipotent adult progenitor cells, a subpopulation of
      mesenchymal stem cells.
AB  - Mesenchymal stem cells were isolated and a subpopulation of cells--multipotent
      adult progenitor cells--were identified that have the potential for multilineage
      differentiation. Their ability to engraft and differentiate in vivo is under
      investigation.

PMID- 11458513
TI  - The impact of ex vivo cytokine stimulation on engraftment of primitive
      hematopoietic cells in a non-human primate model.
AB  - The impairment of engraftment ability after ex vivo or in vivo stimulation of
      hematopoietic stem cells, potentially related to induction of active cell
      cycling, has recently been a topic of intense interest. Our group has used the
      non-human primate autologous transplantation model and genetic marking to
      investigate a number of questions in hematopoiesis with direct relevance to human
      clinical applications. The issue of a potential reversible engraftment defect
      would have many implications for gene therapy and allogeneic or autologous
      transplantation. Initial in vitro studies with rhesus CD34+ cells indicated that
      after 4 days of stimulatory culture in stem cell factor (SCF), megakaryocyte
      growth and development factor (MDGF), and flt3 ligand (FLT), transfer of the
      cells to SCF alone on retronectin (FN) support resulted in decreased active
      cycling and a halt to proliferation, without a loss of viability or induction of
      apoptosis. We then directly compared the engraftment potential of cytokine
      stimulated cells versus those transferred to SCF on FN alone before reinfusion,
      SCF/G-CSF mobilized CD34+ cells from three animals were split into two parts and
      transduced with either of two retroviral marking vectors for 4 days in the
      presence of SCF/FLT/MGDF on FN. One aliquot was cryopreserved, and the other was
      continued in culture without transduction for 2 days in the presence of SCF alone
      on FN. After total body irradiation, both aliquots were thawed and reinfused into
      each animal. In all animals, the level of marking from the fraction continued in
      culture for 2 days with SCF on FN was significantly higher than the level of
      marking from the aliquot transduced for 4 days without the 2-day period in SCF
      alone. This approach may allow more efficient engraftment of successfully
      transduced or ex vivo expanded cells by avoiding active cell cycling at the time
      of reinfusion.

PMID- 11458514
TI  - Development of a stable retrovirus vector capable of long-term expression of
      gamma-globin mRNA in mouse erythrocytes.
AB  - Gene therapy for patients with hemoglobin disorders such has been hampered by the
      inability of retrovirus vectors to transfer globin genes and the locus control
      region (LCR) into hematopoietic stem cells without rearrangement. In addition,
      the expression from intact globin gene vectors has been variable in red blood
      cells as a result of position effects and retrovirus silencing. We hypothesized
      that by substituting the globin gene promoter for the promoter of another gene
      expressed in red blood cells, we could generate stable retrovirus vectors that
      would express globin at sufficient levels to treat hemoglobinopathies. Transgenic
      mice containing the human ankyrin (Ank) gene promoter fused to the human gamma
      globin gene showed position-independent, copy number-dependent expression of a
      linked gamma-globin mRNA. We generated a "double-copy" Ank/A gamma-globin
      retrovirus vector that transferred two copies of the Ank/A gamma-globin gene into
      target cells. Stable gene transfer was observed in primary primary mouse
      progenitor cells and long-term repopulating hematopoietic stem cells. Expression
      of Ank/A gamma-globin mRNA in mature red blood cells was approximately 8% of the
      level of mouse alpha-globin mRNA. We conclude that this novel retrovirus vector
      may be valuable for treating a variety of hemoglobinopathies by gene therapy if
      the level of expression can be further increased.

PMID- 11458515
TI  - Transendothelial migration of hematopoietic progenitor cells. Role of chemotactic
      factors.
AB  - There is increasing evidence that hematopoietic stem cell mobilization and homing
      is regulated not only by adhesion molecules and cytokines, but also by
      chemotactic factors that support transendothelial migration across the bone
      marrow sinusoidal endothelium. Many receptors for chemotactic mediators belong to
      the family of G protein-coupled seven-transmembrane receptors (7-TMR). Signaling
      via G proteins, particularly Gi proteins, results in a chemotactic response of
      the cells towards a gradient of the corresponding ligand. Recent studies have
      provided evidence for expression of several 7-TMR on immature hematopoietic
      progenitor cells, which potentially mediate chemotactic effects: chemokine
      receptors (e.g., CXCR4, receptor for stromal cell-derived factor-1), receptors
      for lipid mediators (e.g., the cysteinyl leukotriene receptor cysLT1 and the
      peripheral cannabinoid receptor cb2), and receptors for neuroendocrine hormones
      (e.g., the somatostatin receptor sst2). From these studies it can be concluded
      that migration of hematopoietic progenitor and stem cells is controlled by a
      variety of chemotactic factors rather than by a single chemokine (e.g., SDF-1).
      Trafficking of immature hematopoietic cells may require combined and interactive
      regulatory functions of these mediators.

PMID- 11458516
TI  - RD114-pseudotyped oncoretroviral vectors. Biological and physical properties.
AB  - Limited functional expression of the viral envelope receptor is a recognized
      barrier to efficient oncoretroviral mediated gene transfer. To circumvent this
      barrier we evaluated a number of envelope proteins with respect to gene transfer
      efficiency into primitive human hematopoietic stem cell populations. We observed
      that oncoretroviral vectors pseudotyped with the envelope protein of feline
      endogenous virus (RD114) could efficiently transduce human repopulating cells
      capable of establishing multilineage hematopoiesis in immunodeficient mice after
      a single exposure to RD114-pseudotyped vector. Comparable rates of gene transfer
      with amphotropic and GALV-pseudotyped vectors have been reported, but only after
      multiple exposures to the viral supernatant. Oncoretroviral vectors pseudotyped
      with the RD114 or the amphotropic envelopes had similar stability in vitro,
      indicating that the increased efficiency in gene transfer is at the receptor
      level likely due to increased receptor expression or an increased receptor
      affinity for the RD114 envelope. We also found that RD114-pseudotype vectors can
      be efficiently concentrated, thereby removing any adverse effects of the
      conditioned media to the long-term repopulating potential of the target human
      hematopoietic stem cell. These studies demonstrate the potential of RD114
      pseudotyped vectors for clinical use.

PMID- 11458517
TI  - Lineage commitment and maturation induction in normal and leukemic preprogenitor
      cells.
AB  - Analysis of the critical cellular processes of self-generation, commitment, and
      maturation induction ideally requires the use of clonal cultures using cells with
      a capacity to undergo all three processes. Preprogenitor cells from normal mouse
      marrow are proving useful cells for such studies. Cells of a newly established
      cloned leukemic cell line, the GB2, are providing a useful analogous leukemic
      system because GB2 cells form stratified subpopulations of clonogenic cells able
      to be clonally analyzed in vitro in which self-renewal is demonstrable, but in
      which near-normal maturation can be induced by a wide range of hematopoietic
      regulators.

PMID- 11458518
TI  - Telomere length dynamics in normal individuals and in patients with hematopoietic
      stem cell-associated disorders.
AB  - The telomere length in nucleated peripheral blood (PB) cells indirectly reflects
      the mitotic history of their precursors: the hematopoietic stem cells (HSCs). The
      average length of telomeres in PB leukocytes can be measured using fluorescence
      in situ hybridization and flow cytometry (flow FISH). We previously used flow
      FISH to characterize the age-related turnover of HSCs in healthy individuals. In
      this review, we describe results of recent flow FISH studies in patients with
      selected hematopoietic stem cell-associated disorders: chronic myelogenous
      leukemia (CML) and several bone marrow failure syndromes. CML is characterized by
      a marked expansion of myeloid Philadelphia chromosome positive (Ph+) cells.
      Nevertheless, nonmalignant (Ph-) HSCs typically coexist in the bone marrow of CML
      patients. We analyzed the telomere length in > 150 peripheral blood leukocytes
      (PBLs) and bone marrow samples of patients with CML as well as samples of Ph- T
      lymphocytes. Compared to normal controls, the overall telomere fluorescence in
      PBLs of patients with CML was significantly reduced. However, no telomere
      shortening was observed in Ph- T-lymphocytes. Patients in late chronic phase (CP)
      had significantly shorter telomeres than those assessed earlier in CP. Our data
      suggest that progressive telomere shortening is correlated with disease
      progression in CML. Within the group of patients with bone marrow failure
      syndromes, we only found significantly shortened telomeres (compared to age
      adjusted controls) in granulocytes from patients with aplastic anemia (AA).
      Strikingly, the telomere length in granulocytes from AA patients who had
      recovered after immunosuppressive therapy (recAA) did not differ significantly
      from controls, whereas untreated patients and nonresponders with persistent
      severe pancytopenia (sAANR) showed marked and significant telomere shortening
      compared to healthy donors and patients with recAA. Furthermore, an inverse
      correlation between age-adjusted telomere length and peripheral blood counts was
      found in support of a model in which the degree of cytopenia and the amount of
      telomere shortening are correlated. These results support the concept of
      extensive proliferation of HSCs in subgroups of AA patients and suggest a
      potential use of telomere-length measurements as a prognostic tool in this group
      of disorders as well.

PMID- 11458519
TI  - Implications of mutations in hematopoietic growth factor receptor genes in
      congenital cytopenias.
AB  - Mutations in the genes of hematopoietic growth factor receptors as a cause of
      congenital cytopenia, such as congenital amegakaryocytic thrombocytopenia (CAMT)
      or severe congenital neutropenia (CN), are discussed. There are striking
      differences in the relevance of receptor mutations in these diseases. CAMT is a
      rare disease characterized by severe hypomegakaryocytic thrombocytopenia during
      the first years of life that develops into pancytopenia in later childhood. In
      patients with CAMT, we found inherited mutations in c-mpl, the gene coding for
      the thrombopoietin receptor, in 8 out of 8 cases. The type of mutation seems to
      correlate with the clinical course seen in the patients. Functional studies
      demonstrated defective thrombopoietin (TPO) reactivity in hematopoietic
      progenitor cells and platelets in CAMT patients. CN is a group of hematopoietic
      disorders characterized by profound, absolute neutropenia due to a maturation
      arrest of myeloid progenitor cells. About 10% of all patients develop secondary
      MDS/leukemia. The malignant progression is associated with acquired nonsense
      mutations within the G-CSF receptor gene that lead to the truncation of the
      carboxy-terminal cytoplasmic domain of the receptor protein involved in
      maturation of myeloid progenitor cells. This seems to be one important step in
      leukemogenesis in CN patients. CAMT is caused by inherited mutations in c-mpl,
      the gene for the thrombopoietin receptor, which lead to reduced or absent
      reactivity to TPO. In contrast, mutations in the G-CSF receptor in CN are
      acquired and are most probably connected with progression of the neutropenia into
      MDS/leukemia as a result of a loss of differentiation signaling.

PMID- 11458520
TI  - Stem cell transplantation across major genetic barriers.
AB  - Megadose haploidentical transplants, mismatched at three HLA loci, engraft
      rapidly and durably without induction of graft-versus-host disease (GVHD). In
      vitro studies suggest that veto cells, contained in the population of
      hematopoietic progenitors, facilitate this favorable outcome. Cytotoxic T cells,
      not reactive against the recipient but reactive against a third party, are potent
      veto cells and can synergize with the stem cells and facilitate allogeneic bone
      marrow engraftment without GVHD. Experiments with mice deficient in FasL and Fas,
      with transfer of FasL gene and with anti-CD8 antibody, suggest that the veto
      activity associated with cytotoxic T lymphocytes (CTLs) requires simultaneous
      expression of FasL and CD8.

PMID- 11458521
TI  - Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose
      cytotoxic therapy by the graft-versus-tumor effect.
AB  - Conventional allografting produces considerable regimen-related toxicities that
      generally limit this treatment to patients younger than 55 years and in otherwise
      good medical condition. T cell-mediated graft-versus-tumor (GVT) effects are
      known to play an important role in the elimination of malignant disease after
      allotransplants. A minimally myelosuppressive regimen that relies on
      immunosuppression for allogeneic engraftment was developed to reduce toxicities
      while optimizing GVT effects. Pre-transplant total-body irradiation (200 cGy)
      followed by post-transplant immunosuppression with cyclosporine (CSP) and
      mycophenolate mofetil (MMF) permitted human leukocyte antigen (HLA)-matched
      sibling donor hematopoietic cell engraftment in 82% of patients (n = 55) without
      prior high-dose therapy. The addition of fludarabine (90 mg/m2) facilitated
      engraftment in all 28 subsequent patients. Overall, fatal progression of
      underlying disease occurred in 20% of patients after transplant. Non-relapse
      mortality occurred in 11% of patients. Toxicities were low. Grade 2-4 acute graft
      versus-host disease (GVHD) associated with primary engraftment developed in 47%
      of patients, and was readily controlled in all but two patients. Donor lymphocyte
      infusions (DLI) were not very effective at converting a low degree of mixed
      donor/host chimerism to full donor chimerism; however, the addition of
      fludarabine reduced the need for DLI. With a median follow-up of 244 days, 68% of
      patients were alive, with 42% of patients in complete remission, including
      molecular remissions. Remissions occurred gradually over periods of weeks to a
      year. If long-term efficacy is demonstrated, such a strategy would expand
      treatment options for patients who would otherwise be excluded from conventional
      allografting.

PMID- 11458522
TI  - Immunological aspects of haploidentical stem cell transplantation in children.
AB  - Thirty-eight children with high-risk hematological malignancies underwent
      transplantation with megadoses of peripheral mobilized CD34+ cells from
      haploidentical parents (n = 24) or from matched unrelated donors (n = 14). The
      CD34+ cells were isolated to a purity of > 98% using magnetic-activated cell
      sorting. This high purity was associated with an almost complete depletion of T
      lymphocytes. No pharmacological prophylaxis for graft-versus-host disease (GvHD)
      was used, and significant primary GvHD was not seen. A final engraftment was seen
      in all patients. Sixteen patients are alive and disease-free with a median follow
      up of 24 months. The immunological reconstitution was faster in the patients
      transplanted with CD34+ stem cells from the haploidentical donors compared to the
      matched unrelated donors, and the transplantation of large numbers of
      haploidentical CD34+ stem cells seems to be superior to that of the matched
      unrelated donors. The phenotypical and functional analysis of the immune
      reconstitution provided some insights into the biology of transplantation of
      highly purified CD34+ cells. In this article, we summarize our current results
      with the transplantation of highly purified stem cells and discuss possible
      implications for further antileukemic post-transplant therapeutic strategies.

PMID- 11458523
TI  - Dendritic cell-based vaccines in patients with hematological malignancies.
AB  - The epithelial mucin MUC1 is overexpressed on many epithelial malignancies as
      well as on some B-cell lymphomas and multiple myelomas. In the present study, we
      described MUC1 expression also on primary AML blasts. To analyze the presentation
      of MUC1-derived HLA-A2 restricted peptides by primary AML blasts, we induced MUC1
      specific cytotoxic T-lymphocytes (CTLs) in vitro using peptide pulsed dendritic
      cells from HLA-A2+ healthy donors as antigen-presenting cells. These CTLs
      efficiently lysed primary AML blasts that constitutively expressed both MUC1 and
      HLA-A2. The specificity of the CTLs was confirmed in a cold target inhibition
      assay. Our data demonstrate that MUC1-derived peptides are tumor antigens in AML
      which could potentially be used for immunotherapeutic approaches.

PMID- 11458524
TI  - Mobilization of endothelial and hematopoietic stem and progenitor cells by
      adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin
      1.
AB  - The chemokine stroma-derived factor-1 (SDF-1) is produced within the bone marrow
      and mediates chemokinesis and chemotaxis on a variety of cell types that express
      the CXCR4 receptor. SDF-1-responsive cell types include monocytes and
      macrophages, B and T lymphocytes, platelets and megakaryocytes, and CD34+ cells,
      including both hematopoietic progenitors and stem cells. We have used intravenous
      injection of a replication-incompetent adenovector expressing the SDF-1 gene to
      elevate serum levels of SDF-1 in Balb/c and SCID mice. Within 3 to 5 days there
      was a marked leukocytosis, predominantly involving monocytes, and a three-fold
      increase in platelets. In addition, AdSDF-1 mobilized CFU-GM, CFU-s, and cells
      with long-term repopulating potential. We have identified a bone marrow-derived,
      circulating endothelial stem cell characterized by expression of the VEGFR2 (Flk
      1/KDR). This cell exhibits a chemotactic and chemokinetic response to SDF-1 and
      VEGF. We have elevated serum levels of VEGF165 using intravenous adenovector gene
      delivery and compared this to an adenovector expressing angiopoietin-1 alone or
      in combination with VEGF. VEGF elevation was associated with rapid mobilization
      of hematopoietic stem and progenitor cells and a population of Flk-1-positive
      endothelial progenitors. In contrast angiopoietin induced a delayed mobilization
      of endothelial and hematopoietic progenitors. The combination of VEGF and
      angiopoietin produced a more prolonged elevation of these progenitors in the
      circulation with increased proliferation of capillaries and expansion of
      sinusoidal spaces in the marrow.

PMID- 11458525
TI  - Increase in circulating SDF-1 after treatment with sulfated glycans. The role of
      SDF-1 in mobilization.
AB  - SDF-1 is a potent chemoattractant for mature white blood cells and hemopoietic
      stem/progenitor cells (HPCs). An important role for this chemokine in
      mobilization has been postulated, but in vivo studies directly addressing its
      effects are lacking. After one injection of fucan sulfate (FucS) or dextran
      sulfate, plasma levels of SDF-1 are greatly increased in mice or primates.
      Increases are dose-dependent and correlate with mobilization of HPCs. Elevated
      levels of circulating SDF-1 appear to be uniquely associated with this treatment,
      as it was not seen with cytokine or anti-integrin antibody treatments that induce
      mobilization. In vitro, these sulfated glycans specifically bind to SDF-1 and
      inhibit SDF-1/heparin binding, suggesting a mechanism of release from
      sequestration on heparan sulfate proteoglycans in vivo. Although other chemokines
      including IL8 and cytokines like G-CSF also increase, evidence in GCSFR-deficient
      mice suggests that at least these two factors are unlikely participants in FucS
      induced mobilization. Likewise, although the activity of the metallo-protease
      MMP9 increases after FucS treatment, experiments in MMP9-/- mice indicate its
      presence is dispensable for mobilization or SDF-1 release. However, effects of
      other proteases cannot be ruled out by these experiments. Finally, anti-SDF-1
      antibodies partially inhibit FucS-induced mobilization, supporting a causative
      relationship. Our data offer a unique insight into the mechanism of sulfated
      glycan-induced mobilization and suggest a novel way of disturbing SDF-1 gradients
      between bone marrow and peripheral blood.

PMID- 11458526
TI  - Stem cell engraftment strategies.
AB  - The donor stem cell phenotype and host microenvironment determine the outcome of
      a stem cell transplant. In a series of transplant studies in syngeneic male to
      female or congenic Ly5.1/Ly5.2 models in which hosts have received no or minimal
      irradiation (100 cGy), evidence overwhelmingly supports the concept that
      syngeneic engraftment is determined by stem cell competition. These approaches
      can be extended to H-2 mismatched allogeneic mouse combination when antigen pre
      exposure and CD40-CD40 ligand antibody blockage are employed. A human trial in
      patients with resistant neoplasia infusing pheresed blood with 10(8) CD3 cells/kg
      showed that tumor responses and complete chimerism occur with very low levels of
      CD34+ cells/kg and that the extent of previous treatment is a critical factor in
      determining chimerism. A major feature of transplants is the phenotype of the
      donor stem cell. This phenotype shows dramatic reversible plasticity involving
      differentiation, adhesion protein expression, and engraftment with cytokine
      induced cell-cycle transit. Homing is probably also plastic. Marked fluctuations
      in engraftment capacity are also seen at different points in marrow circadian
      rhythm.

PMID- 11458527
TI  - Characterization of human hematopoietic cells with short-lived in vivo
      repopulating activity.
AB  - Recent studies with purified hematopoietic stem cells in vitro support a model of
      stem cell self-renewal control that involves distinct mechanisms regulating
      permissiveness to and execution of lineage restriction. Such a model predicts the
      existence of phenotypically separable populations of hematopoietic cells that are
      pluripotent and either capable or incapable of extensive self-renewal. Such
      populations have been previously described in the mouse. We describe here the
      first evidence that such cells can now be identified in humans using different
      types of immunodeficient mice as hosts.

PMID- 11458528
TI  - Divisional history and pluripotency of human hematopoietic stem cells.
AB  - To maintain self-renewal and multilineage differentiation capacity, hematopoietic
      stem cell (HSC) proliferation requires both symmetric and asymmetric cell
      divisions. We have applied a time-lapse camera system and our single-cell culture
      to correlate early replication behavior with short- and long-term function. Using
      five-dimensional flow cytometry to purify subpopulations of fetal liver (FLV),
      fetal bone marrow (FBM), umbilical cord blood (UCB), adult bone marrow (ABM), and
      mobilized peripheral blood (MPB), we studied the relationship between colony
      efficiency (CE) growth pattern and ontogenic age. The highest CE was found among
      HSC candidates from FLV, FBM, and UCB and the lowest from ABM. Relating the
      divisional behavior with functional readouts, we demonstrated that although
      mitotic rate, colony efficiency, and percent of asymmetric divisions all
      decreased with ontogenic age, the fraction of cells undergoing asymmetric
      divisions was consistently at 45%. After 10 days of culture, 60.6 +/- 9.8% of the
      PKH bright cells gave rise to colonies (15.8 +/- 7.8% dispersed) compared to 15.9
      +/- 11.1% of the PKH dim cells (2.5 +/- 2.5% dispersed). In addition, the much
      more primitive Myeloid-Lymphoid Initiating Cells (ML-IC) are predominantly found
      in the PKH-bright population. Thus, primitive function of individual candidate
      HSCs closely related to their divisional behavior.

PMID- 11458529
TI  - Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull
      NOD/SCID mice. The role of SDF-1/CXCR4 interactions.
AB  - The mechanism of hematopoietic stem cell migration and repopulation is not fully
      understood. Murine fetuses that lack the chemokine stromal-derived factor one
      (SDF-1null) or its receptor CXCR4 (CXCR4null) have multiple defects that are
      lethal, including impaired bone marrow hematopoiesis. These results suggest a
      major role for SDF-1/CXCR4 interactions in murine stem cell homing from the fetal
      liver into the bone marrow and its repopulation during development. SDF-1 is
      highly conserved between different species. Human and murine SDF-1 are cross
      reactive and differ in one amino acid. Recently, we reported that SDF-1 and CXCR4
      are essential for homing and repopulation of immune-deficient NOD/SCID and
      B2mnull NOD/SCID mice by human stem cells. In addition, immature human CD34+
      cells and primitive CD34+/CD38-/low cells, which do not migrate toward a gradient
      of SDF-1 in vitro, and do not home and repopulate in vivo the murine bone marrow,
      can become functional repopulating cells by short-term 16-48 hr in vitro
      stimulation with cytokines such as SCF and IL-6 prior to transplantation. These
      cytokines increase surface CXCR4 expression, migration toward SDF-1, and in vivo
      homing and repopulation. We discuss the pleiotropic roles of SDF-1/CXCR4
      interactions in human stem cell migration, development, and repopulation in
      transplanted immune-deficient mice.

PMID- 11458530
TI  - Ex vivo expansion and engraftment potential of cord blood-derived CD34+ cells in
      NOD/SCID mice.
AB  - For more than 10 years umbilical cord blood (UCB) has been used as an alternative
      source of hematopoietic stem cells for allogeneic transplantation. Although the
      clinical results are encouraging, UCB is associated with delayed engraftment. To
      address these issues we have used the NOD/SCID mouse model to study the
      engraftment potential of cord blood cells in more detail, to assess the
      engraftment potential of expanded megakaryocytic progenitor cells, and to study
      the effect of co-transplantation of mesenchymal stem cells on engraftment.

PMID- 11458531
TI  - Regulation of hemangioblast development.
AB  - The in vitro differentiation of embryonic stem (ES) cells provides a powerful
      approach for studying the earliest events involved in the commitment of the
      hematopoietic and endothelial lineages. Using this model system, we have
      identified a precursor with the potential to generate both primitive and
      definitive hematopoietic cells as well as cells with endothelial characteristics.
      The developmental potential of this precursor suggests that it represents the in
      vitro equivalent of the hemangioblast, a common stem cell for both lineages. ES
      cells deficient for the transcription factor scl/tal-1 are unable to generate
      hemangioblasts, while those deficient for Runx1 generate reduced numbers of these
      precursors. These findings indicate that both genes play pivotal roles at the
      earliest stages of hematopoietic and endothelial development. In addition, they
      highlight the strength of this model system in studying the function of genes in
      embryonic development.

PMID- 11458532
TI  - Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and
      conditioning factors.
AB  - The development of addiction and vulnerability to relapse following withdrawal is
      proposed to be the result of neuroadaptive processes within the central nervous
      system that oppose the acute reinforcing actions of drugs of abuse. These changes
      lead to impairment in the mechanisms that mediate positive reinforcement and the
      emergence of affective changes such as anxiety, dysphoria, and depression during
      withdrawal. Considerable evidence exists implicating perturbations in DA and 5-HT
      transmission in the nucleus accumbens--neurochemical systems that are activated
      by cocaine and ethanol self-administration and deficient during withdrawal--as
      potential substrates for these affective changes. In addition, growing evidence
      suggests that enhanced CRF release in the central nucleus of the amygdala
      represents a mechanism underlying the anxiogenic and stress-like consequences of
      withdrawal that are common to all drugs of abuse. A growing body of evidence also
      implicates dysregulation of the non-neuroendocrine CRF stress system within the
      central nucleus of the amygdala as a common factor in the anxiogenic and aversive
      consequences of withdrawal from drugs of abuse. Moreover, a possible link may
      exist between long-lasting abnormalities in CRF function in the CeA and
      vulnerability to relapse during protracted abstinence. Another presumably
      critical element contributing to the chronic relapsing nature of drug addiction
      is the learned responses to drug-related stimuli. The long-lasting efficacy of
      drug- and alcohol-associated contextual stimuli in eliciting drug-seeking
      behavior in animal models of relapse resembles the endurance of conditioned cue
      reactivity and cue-induced cocaine craving in humans and confirms a significant
      role of learning factors in the long-lasting addictive potential of cocaine. With
      cocaine, D1-dependent neural mechanisms within the medial prefrontal cortex and
      basolateral amygdala may be important substrates for the motivating effects of
      drug-related environmental stimuli. With ethanol, available data suggest a role
      for opioid receptors in the mediation of conditioned drug-seeking behavior.
      Finally, conditioning factors (i.e., exposure to drug-associated stimuli) and
      stress can interact to augment vulnerability to relapse. This finding emphasizes
      that it will be important to consider the simultaneous effects of multiple
      environmental triggers for relapse in the development of treatment and medication
      strategies.

PMID- 11458533
TI  - Substance P modulates cocaine-evoked dopamine overflow in the striatum of the rat
      brain.
AB  - To study the role of the neuropeptide substance P in modulating some of the
      effects of cocaine in the striatum, we administered cocaine to rats and measured
      preprotachykinin-A (PPT-A) messenger RNA and substance P peptide in the
      nigrostriatal pathway. We also measured the effect of a neurokinin-1 (NK-1)
      receptor antagonist on striatal cocaine-evoked dopamine overflow by in vivo
      microdialysis in freely moving animals. Acute administration of cocaine to naive
      rats (15 mg/kg of body weight) increased preprotachykinin-A mRNA levels in the
      dorsal and ventral aspects of the caudate putamen 4 hours after the
      intraperitoneal injection of cocaine. Concomitantly, in a separate group of
      animals, substance P peptide levels were decreased in the ventral caudate putamen
      and substantia nigra (38% below controls). In a separate experiment, infusion
      through the microdialysis probe of the neurokinin-1 receptor antagonist L-733,060
      significantly decreased cocaine-evoked striatal dopamine overflow (approximately
      50% inhibition at 30 minutes after cocaine administration). Taken together, these
      results suggest a direct role for substance P in the modulation of some of the
      actions of cocaine in the striatum of the rat brain.

PMID- 11458534
TI  - Neurokinin-1 receptor antagonists block acute cocaine-induced horizontal
      locomotion.
AB  - Systemic exposure to neurokinin-1 receptor antagonists CP099994 or LY306740 prior
      to cocaine administration (10 mg/kg i.p.) blocks acute, cocaine-induced
      horizontal locomotion. CP099994 (30 mg/kg) was delivered i.p. 30 minutes before
      cocaine exposure, and LY306740 (5 mg/kg) was delivered continuously by osmotic
      minipump for 12-14 hours before cocaine administration. These results suggest
      that endogenous substance P acting via neurokinin-1 receptors is necessary for
      the expression of acute cocaine-induced hyperactivity.

PMID- 11458535
TI  - Endocrinological basis of sex differences in cocaine-induced behavioral
      responses.
AB  - Currently, 1.8 million Americans use cocaine, 30% of whom are females. Sex
      differences in the pattern of cocaine abuse may reside in neuroendocrinological
      modulations that affect the use of and/or dependence on cocaine. This review
      discusses sex differences in cocaine-induced behavioral and molecular alterations
      in the central nervous system, with emphasis on the role of endocrine responses
      in the neuronal modulations of this drug. Mechanisms and data supporting the role
      of the hypothalamic-gonadal axis in the modulation of cocaine-induced behavioral
      and molecular alterations are also provided.

PMID- 11458536
TI  - Gender differences in the behavioral responses to cocaine and amphetamine.
      Implications for mechanisms mediating gender differences in drug abuse.
AB  - When ovariectomized female rats receive estrogen, the response to the psychomotor
      stimulants amphetamine or cocaine is enhanced. Estrous cycle-dependent
      differences in amphetamine-stimulated behaviors and striatal dopamine release are
      also noted. Intact female rats exhibit a greater behavioral response to
      amphetamine on estrus than they do on other days of the cycle. Ovariectomy
      results in attenuation of amphetamine-induced behavior and the striatal dopamine
      response to amphetamine. Physiological doses of estrogen given to ovariectomized
      rats reinstate both of these responses to a level comparable to that in estrous
      females. Furthermore, a sex difference is noted, in that females tend to exhibit
      a greater behavioral response to the psychomotor stimulants, and estrogen
      enhances this sex difference. Repeated treatment with amphetamine or cocaine
      produces a progressive increase in behavioral responsiveness with subsequent drug
      administration, a process known as sensitization. In rodents, behavioral
      sensitization results in increases in both frequency and duration of psychomotor
      behaviors such as rotational behavior, stereotyped grooming, headbobs, and
      forelimb movements. Interestingly, females display greater sensitization of
      behaviors in response to psychomotor stimulants than do males. Previous research
      results are summarized, and new results are presented, demonstrating that
      estrogen selectively enhances components of behavior that exhibit sensitization
      in female rats. Results also indicate gender differences in sensitization
      independent of gonadal hormones, suggesting that the neural systems that undergo
      sensitization are sexually dimorphic.

PMID- 11458537
TI  - Sex, steroids, and stimulant sensitivity.
AB  - The current study investigated ovarian modulation of the locomotor response to
      cocaine in rats. Ovariectomy in females lowered the response to cocaine (10 mg/kg
      i.p.), whereas castration did not change that of males. The locomotor responses
      of prepubertal males and females to cocaine were similar. However, the
      postpubertal sex difference resulted from a fall in cocaine-stimulated locomotion
      in males rather than a rise in females. Neonatal testosterone treatment of female
      rat pups decreased the response to cocaine in adulthood. These findings suggest
      that both the activational and organizational effects of gonadal steroids
      contribute to the greater response of females to cocaine.

PMID- 11458538
TI  - Ovarian hormones modulate cocaine-induced locomotor and stereotypic activity.
AB  - Interactions between ovarian hormones and cocaine may underlie gender and estrous
      cycle differences in cocaine-induced behavioral and neurochemical alterations.
      The aim of this study was to further understand how ovarian hormones modulate
      cocaine-induced behavioral alterations. Ovariectomized rats received acute or
      chronic saline or cocaine (15 mg/kg i.p.) administration and were further
      subdivided into one of four hormone-treatment conditions: cholesterol (vehicle
      control), estrogen, progesterone, or estrogen + progesterone. Overall, acute and
      chronic cocaine administration increased all locomotor measurements (total
      locomotor, ambulatory, and rearing counts). Estrogen administration augmented
      cocaine-induced increases in ambulatory and rearing activity. After chronic
      cocaine administration, rats in the vehicle-control group developed behavioral
      tolerance (exhibited by a decrease in activity) in rearing and ambulatory
      activity. Estrogen replacement not only prevented the development of tolerance in
      ambulatory and rearing activities, but also enhanced total locomotor activity
      (sensitization) in response to chronic cocaine. Progesterone treatment did not
      alter the behavioral responses to acute or chronic cocaine administration.
      Estrogen + progesterone-treated animals had higher counts of locomotor activity
      in response to chronic cocaine than did vehicle-control or progesterone-treated
      rats. In stereotypic behaviors, the different hormonal treatments did not affect
      activity in cocaine- or saline-treated rats after acute or chronic drug
      administration. Plasma levels of cocaine did not change after different hormonal
      treatments. Interestingly, animals' coadministered chronic cocaine and estrogen
      had higher levels of corticosterone than did nonestrogen cocaine-treated rats.
      Thus, it is likely that alterations in HPA activation may underlie the observed
      behavioral differences. In summary, these data suggest that there are
      interactions between ovarian hormones and cocaine-induced behavioral alterations
      in female rats, and they extend previous results by showing that estrogen and
      progesterone affect the development of sensitization.

PMID- 11458539
TI  - Drug addictions. Molecular and cellular endpoints.
AB  - Addiction to alcohol, tobacco, and illicit drugs of abuse continues to be one of
      the most significant medical, social, and economic problems facing our society.
      Since the mid-1960s, addictions have been recognized as diseases. We have
      hypothesized that three domains of factors contribute to the development and
      persistence of addictions: inherited or genetic differences in individual
      physiology, alterations in physiology induced by drugs or alcohol, and
      environmental or developmental factors. Neurochemical alterations in the brain
      caused by addictive drugs have a cellular and molecular basis and, in the setting
      of repeated self-exposure, which can lead to addiction, these changes may be
      persistent or even permanent. Such altered molecular, cellular, and
      neurophysiological "set points" in the brain, in turn, contribute to alterations
      in behavior with implications for the specific addictive diseases.

PMID- 11458540
TI  - Modulation of the behavioral and neurochemical effects of psychostimulants by
      kappa-opioid receptor systems.
AB  - The repeated, intermittent use of cocaine and other drugs of abuse produces
      profound and often long-lasting alterations in behavior and brain chemistry. It
      has been suggested that these consequences of drug use play a critical role in
      drug craving and relapse to addiction. This article reviews the effects of
      psychostimulant administration on dopaminergic and excitatory amino acid
      neurotransmission in brain regions comprising the brain's motive circuit and
      provides evidence that the activation of endogenous kappa-opioid receptor systems
      in these regions opposes the behavioral and neurochemical consequences of
      repeated drug use. The role of this opioid system in mediating alterations in
      mood and affect that occur during abstinence from repeated psychostimulant use
      are also discussed.

PMID- 11458541
TI  - Regulation of opioid receptors by cocaine.
AB  - Cocaine is a widely abused psychostimulant. Its direct actions include inhibition
      of dopamine, serotonin, and norepinephrine reuptake into presynaptic nerve
      terminals, thereby potentiating the actions of these transmitters in the synapse.
      A variety of studies have demonstrated that cocaine can also have profound
      effects on the endogenous opioid system. Compelling evidence points to the
      importance of mu opioid receptors in human cocaine addiction and craving. Animal
      studies support these findings and demonstrate that chronic cocaine
      administration can result in alterations in opioid receptor expression and
      function as measured by changes in critical signal transduction pathways. This
      chapter reviews studies on the regulation of opioid receptors as the result of
      exposure to cocaine.

PMID- 11458542
TI  - Comparison of cocaine- and methamphetamine-evoked dopamine and glutamate overflow
      in somatodendritic and terminal field regions of the rat brain during acute,
      chronic, and early withdrawal conditions.
AB  - Methamphetamine and cocaine are among the most commonly abused psychostimulants.
      Repeated injections of psychostimulants produce behavioral sensitization or
      augmented locomotion in rats. Behavioral sensitization to methamphetamine and
      cocaine is long lasting and persists after cessation of drug treatment. Because
      dopamine and glutamate are major neurotransmitters of the neostriatum, we
      evaluated the profile of cocaine- or methamphetamine-evoked dopamine and
      glutamate overflow in the caudate putamen, nucleus accumbens, ventral tegmental
      area, and substantia nigra compacta of the rat brain. We also compared acute
      exposure to these drugs with chronic treatment and early withdrawal. Acute
      injection of methamphetamine (1 mg/kg of body weight) or cocaine (10 mg/kg)
      resulted in elevated levels of extracellular dopamine in all brain regions
      measured, although the magnitude of increase varied between brain regions.
      Overall, methamphetamine caused more dopamine to accumulate in the extracellular
      space than did cocaine when administered to animals during early withdrawal (7
      days of daily injections and challenge on day 11). For example, a challenge
      injection of methamphetamine produced a greater elevation of extracellular
      dopamine in the caudate putamen when compared to acute (naive) exposure. By
      contrast, a challenge injection of cocaine resulted in dopamine levels in the
      caudate putamen that were lower than those observed for acute exposure. In the
      ventral tegmental area and the substantia nigra compacta, a challenge injection
      of methamphetamine or cocaine resulted in extracellular dopamine levels that were
      lower than those for acute exposure. Thus, it appears that behavioral
      sensitization to cocaine can be sustained during early withdrawal in the absence
      of augmented drug-evoked dopamine overflow. Acute injection of methamphetamine or
      cocaine did not change extracellular levels of glutamate in the neostriatum.
      Cocaine challenge (early withdrawal) increased glutamate overflow in the caudate
      putamen and the nucleus accumbens. In contrast, methamphetamine challenge
      increased glutamate overflow in the caudate putamen, but it decreased glutamate
      in the nucleus accumbens. In the ventral tegmental area and the substantia nigra
      compacta, acute methamphetamine exposure decreased glutamate overflow, but acute
      cocaine exposure increased it. Although amphetamines and cocaine induce similar
      behavioral responses, the results presented here demonstrate that at the
      neurochemical level (neurotransmitter release) they sometimes evoke opposite
      effects depending on the brain region studied and the duration of drug treatment.
      Moreover, the sensitized augmentation of locomotor activity observed by us and
      others in response to a challenge injection of cocaine is not dependent on
      elevation of the extracellular concentration of dopamine in the neostriatum. We
      are currently investigating the hypothesis that cocaine activates peptidergic
      systems of the neostriatum and that these systems modulate the synaptic release
      of dopamine in response to psychostimulants.

PMID- 11458543
TI  - Home is where the heart monitor is. Emerging trends in medical device technology.

PMID- 11458544
TI  - Pregnancy and the drug dilemma.

PMID- 11458545
TI  - Shingles.

PMID- 11458546
TI  - Pet food. The lowdown on labels.

PMID- 11458547
TI  - Arizona man sentenced for selling nitrous oxide.

PMID- 11458548
TI  - Health technology is coming home (and how!).

PMID- 11458549
TI  - New drugs for glaucoma.

PMID- 11458552
TI  - Femara approved as first-line breast cancer therapy.

PMID- 11458553
TI  - New drug fights invasive fungal infection.

PMID- 11458554
TI  - Warning for pregnant women on HIV therapy.

PMID- 11458557
TI  - New schizophrenia drug.

PMID- 11458558
TI  - FDA approves watch-like device to monitor blood sugar levels.

PMID- 11458559
TI  - Serious liver injury. Leading reason for drug removals, restrictions.

PMID- 11458560
TI  - Public-private partnerships. Going into labour.
AB  - Public-private partnerships are one of the government's key policy tools. There
      is little conclusive evidence of the ability of partnerships to manage hospitals.
      The government should launch small pilot projects. Managers and the public need
      to be convinced of the viability and equity of public-private partnerships.

PMID- 11458561
TI  - NHS staffing. Way to go.
AB  - The NHS needs to fill vacancies; the need to regenerate communities should be
      addressed jointly with local groups and organisations. There is much that can be
      done now by the NHS and its partners. A strategic approach and sustainable
      funding are necessary to ensure permanent change.

PMID- 11458562
TI  - US healthcare. Mass production.

PMID- 11458563
TI  - Advice lines. Sweet success.

PMID- 11458564
TI  - Care trusts. The urge to merge.

PMID- 11458565
TI  - Joint appointments. The Janus experience.

PMID- 11458566
TI  - The scrutiny mutiny.

PMID- 11458567
TI  - Freedom of Information Act. Open book.

PMID- 11458568
TI  - Requirements for radiation oncology physics in Australia and New Zealand.
AB  - This Position Paper reviews the role, standards of practice, education, training
      and staffing requirements for radiation oncology physics. The role and standard
      of practice for an expert in radiation oncology physics, as defined by the
      ACPSEM, are consistent with the IAEA recommendations. International standards of
      safe practice recommend that this physics expert be authorised by a Regulatory
      Authority (in consultation with the professional organization). In order to
      accommodate the international and AHTAC recommendations or any requirements that
      may be set by a Regulatory Authority, the ACPSEM has defined the criteria for a
      physicist-in-training, a base level physicist, an advanced level physicist and an
      expert radiation oncology physicist. The ACPSEM shall compile separate registers
      for these different radiation oncology physicist categories. What constitutes a
      satisfactory means of establishing the number of physicists and support physics
      staff that is required in radiation oncology continues to be debated. The new
      ACPSEM workforce formula (Formula 2000) yields similar numbers to other
      international professional body recommendations. The ACPSEM recommends that
      Australian and New Zealand radiation oncology centres should aim to employ 223
      and 46 radiation oncology physics staff respectively. At least 75% of this
      workforce should be physicists (168 in Australia and 35 in New Zealand). An
      additional 41 registrar physicist positions (34 in Australia and 7 in New
      Zealand) should be specifically created for training purposes. These registrar
      positions cater for the present physicist shortfall, the future expansion of
      radiation oncology and the expected attrition of radiation oncology physicists in
      the workforce. Registrar physicists shall undertake suitable tertiary education
      in medical physics with an organised in-house training program. The rapid
      advances in the theory and methodology of the new technologies for radiation
      oncology also require a stringent approach to maintaining a satisfactory standard
      of practice in radiation oncology physics. Appropriate on-going education of
      radiation oncology physicists as well as the educating of registrar physicists is
      essential. Institutional management and the ACPSEM must both play a key role in
      providing a means for satisfactory staff tuition on the safe and expert use of
      existing and new radiotherapy equipment.

PMID- 11458569
TI  - Experimental determination of the diffusion coefficient in two-dimensions in
      ferrous sulphate gels using the finite element method.
AB  - A novel two-dimensional finite element method for modelling the diffusion which
      occurs in Fricke or ferrous sulphate type radiation dosimetry gels is presented.
      In most of the previous work, the diffusion coefficient has been estimated using
      simple one-dimensional models. This work presents a two-dimensional model which
      enables the diffusion coefficient to be determined in a much wider range of
      experimental situations. The model includes the provision for the determination
      of a drift parameter. To demonstrate the technique comparative diffusion
      measurements between ferrous sulphate radiation dosimetry gels, with and without
      xylenol orange chelating agent and carbohydrate additives have been undertaken.
      Diffusion coefficients of 9.7 +/- 0.4, 13.3 +/- 0.6 and 9.5 +/- 0.8 10(-3) cm2h-1
      were determined for ferrous sulphate radiation dosimetry gels with and without
      xylenol orange and with xylenol orange and sucrose additives respectively.

PMID- 11458570
TI  - Comparison study of different head model structures with
      homogeneous/inhomogeneous conductivity.
AB  - Most of the human head models used in dipole localisation research, which have
      been reported in the literature to date, assume a simplified cranial structure
      wherein the head is modelled as a set of distinct homogenous tissue compartments.
      The inherent inhomogeneity of the tissues has so far been ignored in these models
      due to the difficulties involved in obtaining the conductivity characteristics
      with sufficiently high enough spatial resolution throughout the head. A technique
      for developing an inhomogeneous head model based on the generation of pseudo
      conductivity values from the existing but sparse conductivity values is proposed
      in this paper. Comparative studies are conducted on different model structures
      and different mechanisms for generating the pseudo conductivities. An evaluation
      of the results of these studies as reported in this paper, shows that contrary to
      current simplifying assumptions, tissue inhomogeneity has a major influence on
      the computation of electrical potential distributions in the head.

PMID- 11458571
TI  - Temporal binding at gamma frequencies in the brain: paving the way to epilepsy?
AB  - Fast (beta-gamma band 20-100 Hz) rhythms of electrical activity of the brain have
      been suggested to play an important role in perception, cognition and
      consciousness providing temporal binding of neural activities and allowing the
      formation of mental representations. The recent advances in the concept of
      temporal binding and their relation to the theory of neural networks
      (connectionism) are reviewed here as well as some experimental results concerning
      the intensified gamma rhythms and epilepsy. The hippocampal-neocortical gamma
      rhythms are extremely intense and hypersynchronous at onset of the epileptiform
      discharges induced by systemic kainic acid in the rat. Those gamma rhythms are
      followed by a slow rhythm of epileptiform spikes/sharp waves or spike-wave
      complexes ('spike-wave' activity). During spike-wave activity, gamma
      synchronisation is significantly decreased. A novel unifying concept is proposed
      which relates the associative principle of neural networks to the mechanism of
      temporal binding at high frequencies. It suggests that for each memory stored in
      an associative network there is a corresponding quasi-stable state of synchronous
      oscillation at some frequency within the gamma band. It also suggests that
      excessive temporal binding ("over-binding") occurs at seizure onset when
      abnormally intensified and globally synchronous fast activity is often observed.
      "Over-binding" may cause the undesirable formation of false associations due to
      inadequate synaptic modifications. To prevent this process, spike-wave discharge
      develops as an extreme activation of the mechanism capable to desynchronise and
      eventually suppress fast activity and erase the spurious modes of activity
      associated with hypersynchronous gamma rhythms. Thus, spike-wave activity is
      suggested to be the "anti-binding" mechanism. This mechanism is also related to
      the spikes/sharp waves normally occurring in the brain mostly in sleep. It is
      qualitatively similar to the "unlearning" mechanism of Crick and Mitchison
      presumably associated with the PGO spikes of the REM sleep.

PMID- 11458572
TI  - A novel filter bank for biotelemetry.
AB  - In a multichannel biotelemetry system, signals taken from a patient are
      distributed along the available frequency range (bandwidth) of the system through
      frequency-division-multiplexing, and combined into a single composite signal.
      Biological signals that are limited to low frequencies (below 10 Hz) modulate the
      frequencies of respective sub-carriers. Other biological signals are carried in
      amplitude-modulated forms. It is recognized that recovering original signals from
      a composite signal at the receiver side is a technical challenge when a telemetry
      system with narrow bandwidth capacity is used, since such a system leaves little
      frequency spacing between information channels. A filter bank is therefore
      utilized for recovering biological signals that are transmitted. The filter bank
      contains filter units comprising switched-capacitor filter integrated circuits.
      The filters have two distinct and opposing outputs (band-stop (notch) and band
      pass). Since most biological signals are at low frequencies, and modulated
      signals occupy a narrow band around the carrier, notch filters can be used to
      efficiently stop signals in the narrow frequency range. Once the interim channels
      are removed, other channels become well separated from each other, and band-pass
      filters can select them. In the proposed system, efficient filtering of closely
      packed channels is achieved, with low interference, from neighboring channels.
      The filter bank is applied to a system that carries four biological signals and a
      battery status indicator signal. Experimental results reinforce theoretical
      predictions that the filter bank successfully de-multiplexes closely packed
      information channels with low crosstalk between them. It is concluded that the
      proposed filter bank allows utilization of cost-effective multichannel
      biotelemetry systems that are designed around commercial audio devices, and that
      it can be readily adapted to a broad range of physiological recording
      requirements.

PMID- 11458573
TI  - The challenge of converting theory into practice.

PMID- 11458575
TI  - Lectures, learning and the Internet.

PMID- 11458574
TI  - GP postgraduate dermatology training.

PMID- 11458576
TI  - Treating malaria may be too expensive.

PMID- 11458577
TI  - Undergraduate palliative medicine education detailed in university prospectuses
      and Websites.

PMID- 11458578
TI  - Screening for ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is the leading cause of death from gynaecological
      malignancy, with over 800 Australian women dying annually, primarily because of
      late presentation of disease. Although a screening test for this disease is
      attractive, currently none are available for use in the general population. Work
      is underway in relation to the benefit for women at 'higher risk'. OBJECTIVE: To
      provide clear guidelines for screening for ovarian cancer. DISCUSSION: No single
      test currently has the sensitivity or specificity to be used as a population
      screening test for this disease. Nonetheless, for patients at 'high risk' the use
      of Ca125 and transvaginal ultrasound may be of benefit. Results from three major
      international multicentre trials are awaited.

PMID- 11458579
TI  - Is a Pap smear enough?
AB  - BACKGROUND: Cervical cancer is the eighth commonest cancer seen in women in
      Australia. It is largely preceded by precancerous changes, which can be detected
      by exfollative cytology and then treated. Of all Pap smears taken in Australia,
      80-90% are performed within general practice. New technologies (rescreening by a
      computer monitored microscope, and fluid based cytology, as well as human
      papillomavirus DNA testing) are now available as additional tests to the
      conventional Pap smear. OBJECTIVE: To discuss the question of whether GPs should
      offer these additional tests to women having Pap smears. DISCUSSION: Adding the
      two new cytology tests on a routine basis to women being screened would increase
      the detection rate of high grade abnormalities from about 1% of all smears
      diagnosed to 1.05% at a cost of $30 million per annum in Victoria alone. While
      there may be some situations where offering these tests is warranted, the main
      aim of doctors in preventing cervical cancer should still be that of recruitment
      and good Pap smear technique.

PMID- 11458580
TI  - Bowel cancer. Positive expectations for improvements in outcomes.
AB  - BACKGROUND: Colorectal cancer continues to be a major cause of mortality and
      morbidity in people over 50 years of age in the Western world. Age standardised
      incidence and mortality rates are high in Australia and too many patients with
      colorectal cancers are first diagnosed with advanced stage disease. OBJECTIVE:
      The aim of this overview of colorectal cancer is to present the clinical
      epidemiology of colorectal cancer in Australia, review screening strategies and
      demonstrate the benefits of early diagnosis. DISCUSSION: While little change has
      been noted in the cure rate within Australia during the past two decades, there
      are now promising signs that more colorectal cancers are being detected in the
      early stage due to greater community awareness of the disease. The movement to
      establish an effective screening program for colorectal cancer will further add
      to the ability to detect colorectal cancers at the early stages. These
      developments, coupled with improvements in surgical technique and adjuvant
      therapy, will provide real scope to improve treatment, survival and quality of
      life outcomes.

PMID- 11458581
TI  - A view from the other side. A doctor's experience of having lymphoma.
AB  - BACKGROUND: Most doctors will at some point in their lives find themselves 'on
      the other side' in the role of patient. This may pose particular challenges both
      for the individual and for those involved in their treatment. OBJECTIVE: To
      document the personal experience of a doctor becoming a patient grappling with
      the potentially life threatening condition of non-Hodgkins lymphoma. DISCUSSION:
      Being a doctor with a life threatening condition brings all of the familiar
      personal emotional challenges and reactions of any other patient. However, this
      is further compounded by the complex and unfamiliar nature of the relationship
      between the doctor as a patient and their own treating health professionals.
      Developing sound, trusting, and mutually respectful professional relationships is
      essential to ensuring doctors receive the same high quality of care when they
      find themselves in the patient role.

PMID- 11458582
TI  - Urinary tract infections in children. Tips for a family physician.
AB  - BACKGROUND: Urinary tract infections in children are the second most common
      bacterial infection requiring medical attention. Despite this, precise definition
      and management of urinary tract infection in children can be quite evasive for
      the unwary family physician. OBJECTIVE: This article provides a few tips for the
      busy family practitioner to help manage this problem. DISCUSSION: Much debate
      still abounds in relation to this issue. However, untreated urinary tract
      infections in childhood can result in unacceptable morbidity in adulthood. Hence
      aggressive management of urinary tract infections in children and identifying
      children 'at risk' remains our top priority.

PMID- 11458583
TI  - Asthma and COPD. Inhalation therapy--clarity or confusion?
AB  - BACKGROUND: Inhalation therapy is the most effective drug administration route
      for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The
      range of available inhaler devices is wide and choosing the right one for your
      patient can be difficult. OBJECTIVE: This article reviews the available evidence
      on the pros and cons of various inhaler devices, in order to encourage a more
      tailored choice. DISCUSSION: Of the currently available devices, we believe the
      Autohaler is probably the most clinically effective and user friendly. Although
      nebulisers are also clinically effective, they are costly and less easily
      portable. For most situations, the acceptable alternative to a nebuliser is an
      aerosolised metered dose inhaler attached to a spacer. Regardless of inhaler
      device choice, your patient must be able to use the device easily, maintain it,
      and derive clinical benefit. The cornerstone of good asthma and COPD management
      is continual clinical reassessment, including inhaler technique.

PMID- 11458584
TI  - Regional nerve blocks. Part 2--the face and scalp.
AB  - This is the second article in our series on regional nerve blocks. This month the
      use of blocks for procedures on the scalp and face is discussed. The anatomy of
      these areas is reviewed and some tips to make these blocks easier are presented.

PMID- 11458585
TI  - Dislocated shoulder. The Mount Beauty analgesia-free method.
AB  - This technique reduces anterior shoulder dislocation without the need for any
      sedating or narcotic analgesics. It is very helpful in more remote situations and
      is ideal for recurrent dislocation. Fractures must be excluded.

PMID- 11458586
TI  - A case of pubic lice resistant to pyrethrins.
AB  - BACKGROUND: Effective therapeutic protocols for the treatment of pubic lice
      include application of approved insecticidal products to all body and scalp hair,
      retreatment at seven days, and use of mechanical removal of lice and eggs.
      OBJECTIVE: We report here infection with pubic lice in a 43 year old male in
      Australia which failed to be eradicated by adequate therapy with a pyrethrin and
      piperonyl butoxide product. DISCUSSION: Pubic lice collected from the case
      survived after exposure to the same product in vitro. The infestation was cured
      by use of 5% permethrin. This appears to be the first report of Pthirus pubis
      resistant to insecticides, in this case pyrethrins and their synergist, piperonyl
      butoxide.

PMID- 11458587
TI  - Herbal medicine in oncology.
AB  - Over the years cancer has been more complicated by 'wonder cures' than perhaps
      any other condition. Remedies such as laetril, shark cartilage, high dose
      vitamins and many alternative medical practices have been used with little
      evidence of improvement and sometimes worsened outcome. It is disconcerting that
      attempts to scientifically discredit these treatments sometimes result in the
      development of conspiracy theories. However, some plants do contain anticancer
      agents, the vinca alkaloids (derived from the Madagascar periwinkle) and
      paclitaxel (derived from the pacific yew tree) are examples of success stories.
      Extensive screening of tens of thousands of plants has unfortunately revealed
      only a handful of potential cancer cures. An evidence based approach to
      alternative treatment in malignancy is appropriate and this seventh article in
      this series reviews the evidence.

PMID- 11458588
TI  - Herb-drug interaction guide.
AB  - Herbal medicines now fall into the category of complementary medicines. With
      their increasing popularity, a new set of circumstances has arisen--the herb-drug
      interaction. In an effort to streamline the interaction information available,
      the author has designed two charts. The first lists the 21 most popular herbal
      medicines sold in Australia, sourced from the largest natural supplement
      manufacturer in Australia, Bullivant Natural Health Products. The second lists
      the 12 commonly prescribed prescription drug classes. This list was sourced from
      F H Faulding & Co Ltd, together with Australian Prescriber. Specific interaction
      information was collated from a variety of sources--medical and complementary
      medicine journals, pharmacy practice journals and respected phytotherapy texts.
      These tables are excerpts from these charts.

PMID- 11458589
TI  - Falls in the elderly.

PMID- 11458590
TI  - Raised white cell count in a sick adult.
AB  - A 57 year old man presents to the emergency department in acute pulmonary oedema.
      Examination reveals evidence of left heart failure, 1-2 cm cervical, axillary and
      inguinal lymph nodes and mild splenomegaly. A full blood examination is listed in
      Table 1.

PMID- 11458591
TI  - Japanese encephalitis.
AB  - A young couple come to see you for a pretravel consultation. They are planning to
      spend a month backpacking in Thailand over December and January. They have read
      about Japanese encephalitis in travel books and seek your advice on the need for
      vaccination against this disease.

PMID- 11458592
TI  - Is it time? The democratic reform of state medical boards.
AB  - BACKGROUND: In contrast to Britain, there has been very little debate about the
      constitution of medical boards in Australia. While the policy of the British
      Medical Association is that there should be an elected medical majority on the
      General Medical Council, state medical boards in Australia are mostly or entirely
      appointed. Appointments are often made by the Minister for Health of the relevant
      state or territory. OBJECTIVE: This article questions why medical representatives
      on medical boards in Australia are not elected to ensure they are representative
      of the profession. None of the medical boards in Australia have an absolute
      majority of elected members. Other than in the Australian Capital Territory
      (ACT), there are no elections whatsoever. In four of the states or territories
      all the members are either public servants or nominees of the Minister for
      Health. DISCUSSION: The lack of elections to medical boards, and the potential
      for ministerial influence on the appointment of board members, are causes for
      concern.

PMID- 11458593
TI  - The beginnings of life.

PMID- 11458594
TI  - Is it time to include the practice nurse in integrated primary health care?
AB  - BACKGROUND: The new '700 series' Medical Benefit Schedule (MBS) items for general
      practice introduce greatly increased potential for collaboration between general
      practitioners and other health professionals in patient care. AIM: To investigate
      the current perceptions of Australian GPs with respect to the desirability and
      impact of 'sharing care' with nurses and other health professionals. METHOD:
      Survey of a sample of GPs in Queensland and NSW participating in the Department
      of Veterans' Affairs Preventive Care Trial. RESULTS: Fifty-two percent of GPs
      surveyed worked in a practice where a nurse was employed. The main role of the
      practice nurse was to do electrocardiograms, apply dressings, and triage duties.
      Practice nurses played only a minor role in health promotion and education.
      Seventy percent of GPs identified 'cost' and 58% 'lack of a Medicare item' as the
      major disincentives to the employment of a practice nurse. Seventy percent of GPs
      were satisfied with the level of communication with community based health
      professionals outside the practice, with 'time' nominated as the greatest barrier
      to optimal contact. Eighty-two percent of GPs considered other health
      professionals had a role in conducting preventive home visits for the older
      population, with 70% of GPs identifying that these health professionals had the
      potential to identify additional health problems, previously unaddressed.
      CONCLUSION: Study findings demonstrate an acceptance by GPs of the nurses role
      and other health professionals in integrated patient care. Funding is seen as the
      major impediment to the greater utilisation of practice nurses in the general
      practice setting.

PMID- 11458595
TI  - The patient perspective survey. Can consultations for complex health problems be
      enhanced?
AB  - BACKGROUND: Patients with complex health problems pose particular difficulties
      due to the interaction between psychosocial factors and physical disease. The aim
      of this study is to investigate the usefulness of a paper based instrument (the
      Patient Perspective Survey, or PPS) to enhance general practitioner-patient
      communication and patients' self reported coping skills. METHODS: A previously
      validated questionnaire was modified and distributed to a self selected group of
      21 GPs. They recruited 77 patients with complex health problems and asked them to
      complete a PPS questionnaire. The patients then returned for an extended
      consultation to discuss the results of the questionnaire with the GP. Patients
      and GPs subsequently completed PPS evaluation forms. RESULTS: The PPS was useful
      for patients with chronic conditions with mixed physical and psychological
      components. It appeared to enhance the GP-patient relationship and gave patients
      a better understanding of their coping skills. DISCUSSION: Patients with complex
      health problems can use paper based questionnaires to improve the quality of
      communication between themselves and their GPs.

PMID- 11458596
TI  - General practice research and education.

PMID- 11458597
TI  - Understanding the context of general practice research.

PMID- 11458598
TI  - Census 2000 and health care's demographic boom.

PMID- 11458599
TI  - Despite strong growth data, Census 2000 is full of contradictions.

PMID- 11458600
TI  - [Penal, civil, administrative and disciplinary medical responsibility.
      Definitions and basic ideas].

PMID- 11458601
TI  - [Medical secrecy].

PMID- 11458602
TI  - [Low back pain. Diagnostic approach].

PMID- 11458603
TI  - [Hyperthyroidism. Etiology, physiopathology, diagnosis, evolution, treatment].

PMID- 11458604
TI  - [Menopause. Diagnosis, consequences, principles of treatment].

PMID- 11458605
TI  - [Dietary assessment for obese patients in current clinical practice: optional,
      recommended, or mandatory?].

PMID- 11458606
TI  - [At the dawn of medicine, a question: boy or girl?].

PMID- 11458607
TI  - [Physiology of intestinal absorption].
AB  - Hydrolysis of dietary constituents is necessary to allow nutrients absorption by
      the small intestinal enterocytes. The digestion process takes place in the
      intestinal lumen, in the brush border membrane, in the enterocyte, and is
      mediated by a large number of hydrolases secreted in the gastrointestinal tract
      or produced by the epithelial cells and localized in the brush border. Nutrients
      are essentially absorbed via a transcellular route across enterocyte cell
      membranes to enter bloodstream or lymphatic circulation. Transport of nutrients
      across apical or basolateral membranes occur by active or facilitated mechanisms
      involving specific transporters. Water, electrolytes and small molecules can be
      partly absorbed via paracellular pathway. Tight junction permeability is
      regulated by osmolarity of intercellular space, definite nutrient concentrations
      in lumen, and activity of brush border membrane transporters.

PMID- 11458608
TI  - [Clinical and biological syndrome of intestinal malabsorption: diagnostic tests].
AB  - Malabsorption has miscellaneous clinical and biological presentations. They may
      vary according to the site of the absorption abnormality (luminal, parietal,
      vascular transport), its type and severity. The problem of the physician is to
      become alerted to the possibility of malabsorption in patients who present with
      signs and symptoms which may be the concern of almost any specialist beside
      gastroenterologists. Patient history, type of signs and symptoms, physical
      examination and simple biochemical and haematological parameters may be of major
      interest in this regard and will help in the choice of the functional tests to
      perform. They will confirm the presumed malabsorption, precise its type and
      severity and may guide towards its aetiology, the precise diagnosis of which will
      usually require other investigations.

PMID- 11458609
TI  - [Adult celiac disease].
AB  - Celiac disease is much common than previously thought with a prevalence of 1/300,
      but most of cases are poorly symptomatic or silent. Fewer of half of patients
      report diarrhoea as a presenting symptom. In adults, the diagnosis should be
      considered, in case of isolated iron deficiency anaemia, neurological symptoms
      (ataxia, epilepsy), osteoporosis and arthralgia, infertility, dermatitis
      herpetiformis and abnormalities in liver tests. Characteristic histological
      features are total or subtotal villous atrophy associated with an increased
      number of intraepithelial lymphocytes. The most sensitive and specific
      circulating antibodies for the diagnosis are endomysial and transglutaminase IgA
      antibodies. The treatment of celiac disease requires a strict gluten free diet,
      but the observance to this diet is often difficult. In patients refractory to a
      strict gluten free diet, serious complications such as intestinal lymphoma or
      refractory sprue should be considered.

PMID- 11458610
TI  - [Chronic bacterial overgrowth in the small intestine].
AB  - The small intestinal bacterial overgrowth (SIBO) is defined by the presence in
      the proximal part of the intestine of a bacterial population and qualitatively
      abnormal. It is necessary to distinguish the "non-symptomatic" SIBO and the
      "symptomatic" SIBO responsible for a chronic diarrhoea and/or of a malabsorption
      syndrome. The main factor encouraging the intervening of a SIBO is the stasis of
      the intestinal juice. The gold standard test to confirm the diagnosis of SIBO is
      the jejunal bacteriological intubation, but it is about a trying and expensive
      method. It is currently supplanted by the respiratory test to hydrogen after
      ingestion of glucose that is simple, no invasive and little expensive. The
      treatment usually consists on the repeated administration of antibiotics and
      nutritional support.

PMID- 11458611
TI  - [Specific carbohydrate malabsorption].
AB  - Specific malabsorption of carbohydrate is related to the lack or decrease in
      enzymatic activity needed for its hydrolysis; seldom, it is related to the lack
      or overloading in transport mechanism of monosaccharide. Ingestion of unabsorbed
      carbohydrate may induce digestive symptoms due to its colonic fermentation
      (borborygmus, bloating, pain, and flatus) or its osmotic activity (diarrhoea). In
      a patient consuming at least a bowl of milk per day and suffering of functional
      digestive symptoms, intolerance to lactose must be ruled out because its
      treatment is easy and efficient, i.e. to put fermented dairy products in place of
      milk.

PMID- 11458612
TI  - [Maldigestion during chronic pancreatitis].
AB  - During chronic pancreatitis exocrine pancreatic insufficiency develops leading to
      a loss of pancreatic enzymes in the duodenum, especially pancreatic lipase. As a
      result, lipid maldigestion occurs (on a clinical standpoint it is more serious
      than proteic maldigestion) responsible for greasy diarrhoea with steatorrhoea and
      abdominal discomfort. Stearorrhoea is diagnosed thanks to a direct measurement of
      the total lipid content in the stool rather than indirect test. The pancreatic
      origin of the steatorrhoea is demonstrated in view of the clinical history of the
      disease, the normal duodenal biopsy specimen or by imaging or biological testing.
      Steatorrhoea is treated by pancreatic extract given as a form of enteric coated
      microcapsules (which are protected from proteolitic and acidic digestion)
      together with some dietary advises.

PMID- 11458613
TI  - [Intestinal failure].
AB  - Intestinal failure is defined as the reduction in the functioning gut mass below
      the minimal amount necessary for the absorption of nutrients and a normal
      nutritional status. The main cause of chronic intestinal failure in adults is
      short bowel syndrome secondary to mesenteric ischemia. In short bowel the remnant
      bowel length is inferior to 200 cm. The two other causes of intestinal failure
      are extensive small bowel mucosal diseases and chronic intestinal pseudo
      obstruction. The reference treatment of severe chronic intestinal failure is home
      parenteral nutrition. The main alternate for irreversible intestinal failure is
      small bowel transplantation, isolated or combined to liver transplantation.

PMID- 11458615
TI  - [Advice for students at the end of the training].

PMID- 11458614
TI  - [Intestinal malabsorption in the child].
AB  - Intestinal malabsorption in the child usually manifests by chronic diarrhoea and
      (or) deficiency of growth and weight gain. Given the wide diversity of causes,
      diagnosis is primarily based on history-taking and clinical examination, which
      subsequently directs investigations. Stool examination was long the reference to
      confirm malabsorption and to determine its mechanisms: impaired digestion
      (external pancreatic insufficiency), malabsorption (intolerance to cow's milk
      proteins or to gluten), fermentation (intolerance to primary or secondary
      sugars). Presently, however, the diagnosis is usually made on the basis of
      several simple examinations.

PMID- 11458616
TI  - [Mechanism and clinical expression of graft rejection and graft-versus-host
      disease].

PMID- 11458617
TI  - Preventive dental care for children and adolescents.
AB  - Preventive dental care for children and adolescents requires a good understanding
      of the dental caries process and the particular relationships that exist
      throughout childhood and young adulthood. Only when these relationships are
      understood can they be used to diagnose dental caries risk and apply appropriate
      preventive therapies and restorative care that is effective. The need to diagnose
      risk when applying preventive care is as important for individual patients as it
      is for population groups. At the individual level, the aim is to aid the
      development of a healthy functioning dentition for life. This applies in the
      population group level but the cost benefits also become important in justifying
      the funding to carry out preventive practices. Risk can be determined by general
      factors including the socioeconomic status, access to optimally fluoridated
      drinking water and age. Specific factors include the microbiology of the dental
      plaque, dietary practices, oral hygiene practices, individual fluoride use and
      previous dental caries history. Once the risk has been diagnosed and the related
      factors identified, the best preventive approach can be selected. This may
      include oral hygiene, dietary change, fluoride recommendations, restorative care
      using fluoride releasing materials or antibacterial mouthwashes. The dentist may
      play several roles in preventive dental care. The first is as the giver of advice
      and care for the individual child patient; the second is as an advocate to help
      the child get the care by getting the consent and support of the parents; and the
      third may be to lobby for the appropriate funding to obtain this care in publicly
      funded programs.

PMID- 11458618
TI  - Immunohistochemical studies of Na+/I- symporter in human thyroid tissues--a
      correlation with clinical thyroid scintigraphy.
AB  - BACKGROUND: Thyroid Na+/I- symporter (NIS) is thought to play an important role
      in iodide uptake in thyrocytes. We hypothesize that there is correlation between
      the expression of NIS protein in the normal and diseased thyroid tissues and
      their clinical thyroid scintigraphy. METHODS: Twenty-seven patients, aged from 21
      to 81, were studied from the surgical department of a tertiary referral center.
      Ten patients were with papillary carcinoma, 5 with follicular carcinoma, 5 with
      follicular adenoma, 5 with nodular goiter and 2 with Graves' disease. All the
      carcinoma patients underwent total thyroidectomy while others had lobectomy or
      subtotal thyroidectomy. The thyroid tissue sections prepared for study were
      stained with polyclonal hNIS antibody (SS Chiang, Ohio). RESULTS: Most of the
      nodular goiters were negatively stained except 2 samples that showed weak signal
      focally. All cases with follicular adenoma or follicular carcinoma were negative
      for NIS expression, while some with papillary carcinoma were stained positive at
      sporadic follicles with weak signal. The thyroid tissue of Graves' disease was
      stained positive for NIS expression. CONCLUSIONS: Thyroid tissues with
      hypofunctioning nodules displayed significantly reduced or undetectable level of
      NIS expression. It correlated well with pre-operative thyroid scans.

PMID- 11458619
TI  - The pressure waveform of coronary sinus in human hearts.
AB  - BACKGROUND: The pressure waveform of coronary sinus in human hearts has never
      been well described. Retrograde cardioplegia perfusion has become a popular
      method of myocardial protection in recent years, and identification of the
      pressure waveform of the coronary sinus might help intubate the coronary sinus in
      retrograde cardioplegia perfusion by differentiating it from that of the right
      atrium. The purpose of this study is to identify the pressure waveform of the
      coronary sinus. METHODS: We inserted a catheter into the coronary sinus under
      direct vision via a right atriotomy after completion of open heart operation in
      eight patients. The pressure waveforms of coronary sinus and central venous line,
      as well as the electrocardiogram (EKG), were recorded simultaneously after the
      patient was stable and weaned from the cardiopulmonary bypass. The recorded
      pressure waveforms of coronary sinus and central venous line were compared.
      RESULTS: The pressure waveform of coronary sinus was found to have three peaks,
      more prominent than those of the central venous line waveform. CONCLUSIONS: The
      pressure waveform of coronary sinus could be distinguished from that of the
      central venous line. The difference might help coronary sinus cannulation for
      retrograde cardioplegia perfusion.

PMID- 11458620
TI  - Sonographic features of breast abscesses with emphasis on "hypoechoic rim" sign.
AB  - BACKGROUND: There are only limited reports on the ultrasound (US) features of
      breast abscess. The purpose of this paper is to review the US features of breast
      abscess with emphasis on "hypoechoic rim" sign which is more commonly seen in
      chronic abscess. METHODS: In a period of 10 years, 20,998 patients were referred
      for breast US examinations. Medical records identified 204 patients in whom
      breast abscess was diagnosed. All patients were examined using high-resolution
      real-time US scanners. The initial ultrasound reports and hard copy images were
      all carefully reviewed. The grading of the echogenicity of the abscess was
      classified from grade 0 to grade 5. The contours of the lesions were described as
      smooth, macrolobulated, microlobulated, irregular, zigzag, spiculate or
      indistinct. The wall thickness was measured to document the presence of
      "hypoechoic rim" which denoted a wall thickness greater than 2 mm. The associated
      findings and other acoustic phenomena related to the lesion were recorded.
      RESULTS: One hundred and thirty-six patients (136/204) having specific aspiration
      and/or biopsy/histopathological results were included in the study. All of the
      136 patients showed abnormal US findings (100%). Most lesions showed grade 1 or
      grade 2 echogenicity (117, 86%). The contour of the abscess was usually smooth
      (42, 31%), macrolobulated (42, 31%), or irregular (22, 16%). A hypoechoic rim was
      noticed in 18 lesions (13%). Focal skin thickening was chiefly noticed in 91% of
      superficial abscesses (39/43) and 17% of intramammary abscesses (14/84). Diffuse
      skin thickening was exclusively evident in the breasts coexisting with mastitis.
      Hypoechoic interstitial streaks were not a common finding (7%), occurring in
      acute abscesses. The other findings included surrounding hypoechoic amorphous
      tissue (26%), posterior wall enhancement (71%), distal enhancement (60%) and
      lateral shadows (57%). CONCLUSIONS: US plays an important role in confirmation of
      the clinical diagnosis of breast abscess and aids significantly in the management
      of inflammatory breast diseases. Presence of the hypoechoic rim surrounding a
      fluid space or a central area of low-level echoes (i.e., grade 1 to grade 3) is
      indicative of a chronic abscess.

PMID- 11458621
TI  - Ventilator-associated pneumonia with circuit changes every 2 days versus every
      week.
AB  - BACKGROUND: Frequent ventilator circuit changes are expensive and sometimes
      unnecessary. Following the worldwide trend to lengthen the intervals for
      ventilator circuit change from 2 days to 1 week, this study aims to assure that
      low rate of ventilator-associated pneumonia (VAP) can be maintained with cost
      containment. METHODS: Ventilator circuits were routinely changed every 7 days in
      the study period for 2 years and every 2 days during the historical control
      period of another 2 years. Pediatric patients (age less than 15 years) were not
      included. Nosocomial pneumonia was diagnosed by the criteria of the Centers of
      Disease Control and Prevention (CDC) of the United States (US). VAP was
      identified by combining and comparing 2 databases from the Respiratory Therapy
      Department and the Infection Control Unit of our hospital. RESULTS: In the study
      group, 225 episodes of pneumonias were observed in 7,068 patients and 87,338
      ventilator days. The rate of VAP was 2.58 per 1,000 ventilator days. There were
      174 episodes of pneumonia in 6,213 patients and 65,467 ventilator days of the
      control group. The rate of VAP was 2.66 per 1,000 ventilator days. The difference
      between both groups was not significant (p = 0.803). Yet, the cost curbed was
      around 80,000 US dollars per year. CONCLUSIONS: Extending ventilator circuit
      change interval from 2 days to 7 days do not increase the risk for VAP, but the
      cost savings for labor and supply are substantial.

PMID- 11458622
TI  - Clinical spectrum of Kawasaki disease in infants.
AB  - BACKGROUND: Kawasaki disease is a common acquired heart disease in children. Only
      a few reports have been published concerning Kawasaki disease in infants. This
      study was performed to assess the clinical spectrum of Kawasaki disease in
      infants. METHODS: Between January 1989 and December 1998, a total of 48
      consecutive Kawasaki patients less than one year of age were enrolled and studied
      retrospectively. Coronary artery dilation was defined as the internal diameter of
      a coronary artery larger than 3 mm. All cases received 2 gm/Kg of intravenous
      immunoglobulin. We divided the patients into two groups; group I; coronary artery
      dilation (+) and group II; coronary artery dilation (-), and compared the
      clinical and laboratory data. RESULTS: Of 273 patients with Kawasaki disease, 48
      (17.5%) were less than one year of age. Among these patients (< 1 year old), the
      median age was 7.8 +/- 2.8 months (range 2 months to 12 months), and the male to
      female ratio was 1.52:1. The incidence of atypical Kawasaki disease was 31.2%
      (compared with an incidence of atypical Kawasaki disease among patient more than
      one year of age of 7.5%; p < 0.001), and that of coronary artery dilation was
      35.4%. Clinical manifestations included fever 100%, extremity change 91.6%, skin
      rash 89.6%, conjunctivitis 89.6%, oral mucosa change 89.6%, and cervical
      lymphadenopathy 0%. Laboratory data revealed white blood cell count: 15,403 +/-
      6,282/mm3, hemoglobin: 10.1 +/- 1.0 gm/dl, neutrophil: 59.2 +/- 13.7%,
      lymphocytes: 30.6 +/- 13.1%, platelet count: 456,3000 +/- 216,4000/mm3, and C
      reactive protein 8.2 +/- 5.6 mg/dl. Patients with coronary artery dilation had a
      longer duration of diagnosis, higher incidence of atypical presentation, lower
      incidence of conjunctivitis, lower incidence of skin rash, lower incidence of
      extremity change, and lower C-reactive protein. The predictive value of coronary
      artery dilation based on the combination of atypical presentation, duration of
      diagnosis, and C-reactive protein was 81.2%. CONCLUSIONS: Kawasaki disease in
      infants is associated with a high incidence of atypical presentation and
      increased risk of coronary artery dilation. We suggest that in an infant with
      insufficient diagnostic criteria for Kawasaki disease, care should be taken to
      avoid missing atypical Kawasaki disease. Echocardiography is an important tool
      for diagnosis of atypical Kawasaki disease.

PMID- 11458623
TI  - Huge cystic duplication of the ascending colon in adult.
AB  - Duplications of alimentary tract are uncommon congenital anomalies that are
      usually identified during the pediatric age. However, a minority of cases remain
      unsuspected until adulthood. They may be cystic or tubular in appearance and
      characteristically arise from the mesenteric border of the intestine. This paper
      reports a 37-year-old male with a huge cystic duplication of the ascending colon.
      In facing such a huge abdominal cystic tumor, differential diagnoses including
      duplication cyst, mesenteric cyst, choledochal cyst, giant diverticulum, and
      cystic tumor of the pancreas should be considered. Computerized tomography is a
      good tool for delineating the relationship between the tumor and peripheral
      structures. Surgery not only provides treatment but also final pathological
      diagnosis. Complete resection of a colonic duplication is necessary because of
      potential malignant change of the lesion.

PMID- 11458624
TI  - Successful pregnancy after missing HCG injection in in vitro fertilization and
      embryo transfer.
AB  - We reported a rare case of successful pregnancy and delivery of healthy twins
      after salvage injection of the human chorionic gonadotropin (HCG) for empty
      follicular syndrome because of missing scheduled HCG injection in the in vitro
      fertilization and embryo transfer cycle.

PMID- 11458625
TI  - Primary renal sarcoma with inferior vena cava thrombus presenting with tumor
      rupture.
AB  - Primary renal sarcoma represents approximately one per cent of all primary tumors
      of the kidney in adults. We report an unusual case of primary renal sarcoma with
      inferior vena cava (IVC) thrombus. This patient presented with hemorrhagic shock
      due to tumor rupture. Emergent radical nephrectomy and vena caval thrombectomy
      were performed. Histological examination proved a clear cell sarcoma.

PMID- 11458626
TI  - Multiple pleural nodules without effusion--a rare presentation of tuberculous
      pleurisy.
AB  - We report a rare case of tuberculous pleurisy presenting with multiple pleural
      nodules without associated effusion or parenchymal lung lesions. A 62-year-old
      man had multiple discrete pleural nodules in the right hemithorax on chest
      radiography without any clinical symptoms. Thoracoscopic biopsy of the pleural
      nodules revealed a caseous granuloma with acid-fast bacilli. The patient received
      antituberculous therapy, with resolution of tuberculomas on chest film within 2
      months. To our knowledge, only two similar cases have been previously reported in
      the English literature, and our observation should lead to broadening of the
      spectrum of the differential diagnosis of multiple pleural nodules.

PMID- 11458627
TI  - The role of specific emotions in children's responses to interparental conflict:
      a test of the model.
AB  - Mothers, fathers, and their 6-year-old children (N = 164) participated in a study
      testing key tenets of the specific emotions model of marital conflict. Parents
      reported their marital conflict strategies, were observed interacting with their
      children, and rated children's behavioral adjustment. Children reported their
      emotional reactions to specific interparental conflicts. Results support the
      specific emotions model. Children's behaviors mirrored the marital or parental
      behaviors of same-gender parents. Indirect effects of marital aggression through
      parental behavior were detected, and marital and parental behaviors interacted to
      predict girls' externalizing. Girls' anger, sadness, and fear increased with
      fathers' marital aggression. Fear and the anger by fear interaction predicted
      girls' internalizing. Fathers' marital aggression interacted with anger to
      predict externalizing and interacted with fear to predict internalizing behavior
      in boys.

PMID- 11458628
TI  - Parental socialization of children's dysregulated expression of emotion and
      externalizing problems.
AB  - The relations of parents' warmth, emotional expressivity, and discussion of
      emotion to 2nd-5th graders' regulation of emotional expressivity, externalizing
      problem behaviors, and expressivity were examined. Parents' and children's facial
      expressions to evocative slides were observed, as was parents' discussion of the
      slides, and parents and teachers provided information on children's regulation of
      expressivity and problem behavior. Analyses supported the hypothesis that the
      effect of parental variables on children's problem behavior was at least partly
      indirect through their children's regulation of emotion. Children's low negative
      (versus positive) facial expressivity to negative slides was associated with
      problem behavior for boys. A reversed model did not support the possibility that
      children's functioning had causal effects on parenting. The findings suggest that
      parents' emotion-related behaviors are linked to children's regulation of
      expressivity and externalizing behaviors.

PMID- 11458629
TI  - Men's work and family lives in India: the daily organization of time and emotion.
AB  - This article examines daily patterns of work and family life for a sample of
      middle-class men in northern India. One hundred fathers of 8th graders provided
      information on their hour-to-hour time use and subjective states, by means of the
      experience sampling method. They reported little time spent on family work but
      substantial amounts of time with their children and thinking about their
      families. At their jobs, they reported high levels of attention but more negative
      emotion. By contrast, the home sphere elicited lower attention, more favorable
      affect, and more feeling of choice. Unlike for American samples, little
      relationship was found between experience at work and home, including little
      influence of men's work emotions on the family in the evening. These findings
      reflect how strong traditional family roles in India shape men's daily lives.

PMID- 11458630
TI  - Predicting expressed emotion: a study with families of obsessive-compulsive and
      agoraphobic outpatients.
AB  - The authors used structural equation modeling to examine expressed emotion (EE)
      in relatives of outpatients with panic disorder with agoraphobia (n = 42) or
      obsessive-compulsive disorder (n = 60). EE was examined as a function of
      patients' illness and personality and as a function of characteristics of
      relatives themselves. EE was operationalized in terms of hostility on the
      Camberwell Family Interview (C. E. Vaughn & J. P. Leff, 1976) and patients'
      ratings of their relatives' criticism (perceived criticism). Key findings include
      the identification of a characteristic of the relative (self-reported angry
      thoughts, feelings, and behaviors) that is directly linked to both hostility
      toward the patient and to perceived criticism, as well as a direct path between
      relatives' low rates of observed problem solving and their hostility toward the
      patient. Patient Pathology predicted perceived criticism but not observer-rated
      hostility.

PMID- 11458631
TI  - Differences between couples who end their marriage by fault or no-fault legal
      procedures.
AB  - Spouses from 53 couples who ended their marriage by dissolution (DS), a form of
      no-fault divorce, were compared with spouses from 59 couples who ended their
      marriage by fault-based divorce (DV). DV husbands were younger than DS husbands.
      DV couples were less likely to have pooled finances, and they had more sons than
      did DS couples. For growth curves over the first 4 years of marriage, relative to
      DS wives, DV wives had lower starting levels for liking of spouse, trust, and
      marital quality; higher starting levels for dysfunctional beliefs about
      relationships and psychological distress; weaker declines in extrinsic motives
      for being married; and stronger declines for love for spouse. Relative to DS
      husbands, DV husbands showed a stronger increase in dysfunctional beliefs about
      relationships.

PMID- 11458632
TI  - Conditions of sibling support in adolescence.
AB  - This study examined the nature and extent of adolescent siblings' supportive
      roles and the conditions under which siblings provide support to one another
      about familial and nonfamilial issues. Data were collected from 185 adolescent
      firstborn (M age = 16 years) and second born (M age = 13 years) sibling pairs. In
      home interviews, siblings reported on family experiences and psychosocial
      functioning during the past year. In a series of 7 evening telephone interviews,
      siblings reported on their shared daily activities. Findings suggested that both
      older and younger siblings view older siblings as sources of support about
      nonfamilial issues such as social and scholastic activities and that siblings
      assume equally supportive roles about familial issues. Further, the results
      suggested that family background characteristics, sibling relationship qualities,
      and adolescents' psychosocial functioning were linked to the nature and extent of
      sibling support.

PMID- 11458633
TI  - Family lives and friendships: the perspectives of children in step-, single
      parent, and nonstep families.
AB  - Children's reports on their experiences in different family settings
      (stepfamilies, single-parent families, and intact families), their contact with
      friends, and the quality of their friendships were studied with data from 238
      children drawn from a community sample. A particular focus was on children's
      confiding and communication: children's recall of communication about family
      transitions and their current communication about stepfamily issues with family
      and friends. Friends were found to be key confidants. The relations between
      children's family lives (confiding, parent-child relationships, family
      activities, involvement in parental conflict, and communication about stepfamily
      issues) and their friendships were investigated and found to be linked to
      biological relatedness and family setting.

PMID- 11458634
TI  - Family structure and the externalizing behavior of children from economically
      disadvantaged families.
AB  - This study examined the relations among family structure, caregiver relationship
      history, aspects of environmental adversity, and teacher reports about the
      externalizing behaviors of 6- and 7-year-old children from economically
      disadvantaged families. Family structure contrasted intact families,
      stepfamilies, single-parent families, and cohabiting families. Problem behaviors
      were more frequent for children from unmarried families than from married
      families and were more frequent for boys than for girls from cohabiting families.
      Relationship history reduced the effects for family structure. Children's
      adjustment varied with both the current status and past stability of caregiver
      intimate relationships for disadvantaged families.

PMID- 11458635
TI  - Developmental, family, and ethnic influences on adolescent alcohol usage: a
      growth curve approach.
AB  - The influence of the developmental process of individuation, family conflict and
      cohesion, and ethnicity on adolescent alcohol use was examined in a 3-year
      longitudinal study. Participants included non-Hispanic White, Mexican American,
      and African American adolescents (n = 6,522) from 6th, 7th, and 8th grades. They
      were surveyed annually for 3 years. Depending on which aspect of individuation
      was measured, hierarchical linear modeling indicated that changes in adolescent
      individuation were related to either increases or decreases in alcohol use over
      the 3-year period. Separation and family conflict were related to increases in
      alcohol use, and intergenerational individuation and family cohesion were related
      to decreases in alcohol use. White and Mexican American adolescents had a faster
      rate of increase in alcohol use than did African American youth. Separation and
      family process similarly influenced adolescent alcohol use from different ethnic
      groups. Implications for prevention and intervention programs are discussed.

PMID- 11458636
TI  - Interparental conflict, children's social cognitions, and child aggression: a
      test of a mediational model.
AB  - Although correlations between interparental conflict and child maladjustment are
      well-established, the processes connecting these 2 phenomena are less understood.
      The present study tested whether an aggressogenic cognitive style mediates the
      relationship between interparental conflict and child aggression. A multiethnic
      sample of 115 families with a child between the ages of 7 and 13 years
      participated. Questionnaires were used to assess parents' and children's
      perceptions of interparental conflict, children's social problem-solving
      strategies and beliefs about aggression, and parent and teacher reports of child
      aggression. Support was found for the mediating effect of aggressogenic
      cognitions on children's school aggression but not on children's aggression at
      home. Implications for understanding the associations among interparental
      conflict, children's social cognitions, and child aggression in different
      environmental contexts are discussed.

PMID- 11458637
TI  - Can questionnaire reports correctly classify relationship distress and partner
      physical abuse?
AB  - Relationship adjustment (e.g., Dyadic Adjustment Scale; DAS) and physical
      aggression (e.g., Conflict Tactics Scale) measures are used both as screening
      tools and as the sole criterion for classification. This study created face valid
      diagnostic interviews for relationship distress and physical abuse, through which
      one could compare preliminarily the classification properties of questionnaire
      reports. The DAS (and a global measure of relationship satisfaction) had modest
      agreement with a structured diagnostic interview; both questionnaires tended to
      overdiagnose distress compared with the interview. Results for partner abuse
      reiterated the need to go beyond occurrence of aggression as the sole diagnostic
      criterion, because men's aggression was more likely than women's to rise to the
      level of "abuse" when diagnostic criteria (injury or substantial fear) were
      applied.

PMID- 11458638
TI  - [Relative genetic effectiveness of fission neutrons in inducing various types of
      recessive mutation in Drosophila melanogaster].
AB  - The RCR-analysis of 53 gamma-Ray- and neutron-induced vg recessive mutations of
      Drosophila melanogaster combined with complementation assay with the vg[nw83b27]
      deletion mutation is used to detect precisely the RGE values of neutrons (0.85
      MeV) under the chromosome and point (at the DNA level) mutation induction.
      Simultaneously, the induction-kinetics of gamma-ray- and neutron-induced
      macrodeletion as well as recessive lethal mutations in the X-chromosome were
      studied. The results obtained have shown that all genetic end-points increase
      linearly with gamma-ray or neutron dose. Thereby, the efficacy of neutrons is
      found to be twice (and more) as large as that of gamma-rays under the all macro-
      and micro-aberration mutation induction (macrodeletions and recessive lethals in
      the X-chromosome, multilocus deletions and intragenic deletions as well). Unlike
      that, the RGE of neutrons are more than twice as low as that of gamma-rays under
      the gene/point mutation induction. This feature of neutrons have been predicted
      as far back as in the early days of the radiation genetics (N.W. Timofeeff
      Ressovsky, K.G. Zimmer, 1938), but experimentally supported at the DNA level just
      now.

PMID- 11458639
TI  - [Post-radiation changes in kinetic parameters of purine-catabolizing enzymes in
      rat blood serum after combined action of external and internal irradiation caused
      by 137Cs].
AB  - Kinetic parameters (Vmax, Km) of enzymes catalyzing the reaction sequence 5'-AMP-
      >adenosine-->inosine-->hypoxanthine in rat's blood serum were studied at
      different postirradiation terms after combined effect of external gamma
      irradiation (1 Gy, 137Cs) and incorporated 137Cs (160 kBq). It was shown that
      radiation-induced changes of kinetic properties of 5'-nucleotidase, adenosine
      deaminase, purine nucleoside phosphorylase were expressed at earlier terms under
      combined radiation effect than it occurred at external gamma-irradiation effect
      only. Postirradiation modification of enzymes kinetics brought about the
      acceleration of 5'-AMP conversion to its endpoint product, hypoxanthine. Negative
      consequences of the postirradiation activation of purine metabolism, in
      particular, the activation of hypoxanthine prooxidant system and the rise of
      clastogenic activity of blood plasma are discussed.

PMID- 11458640
TI  - [Effect of whole-body therapeutic gamma irradiation of patients on molecular
      characteristics of blood plasma from NMR data].
AB  - The changes in molecular characteristics of patients' blood after a totally
      therapeutic irradiation were studied by the NMR method. The changes in the
      intensity and shape of peaks attributed to methylene and methyl protons of fatty
      acids and lipoproteins were found in the NMR spectra of the blood plasma of the
      irradiated subjects. The data on the role of peroxide lipid oxidation in changes
      of lipid concentration in blood plasma were obtained. The changes in the
      composition of metabolites in the blood and their relative equilibrium level were
      found.

PMID- 11458641
TI  - [Radiation-induced genomic instability: phenomenon, molecular mechanisms,
      pathogenetic significance].
AB  - The recent data on the radiation-induced genome instability as a special state of
      progeny of cells irradiated in vitro as well as after a whole body exposure to
      ionizing radiation, that make these cells considerably different from normal,
      unirradiated cells, were considered. This state presents a number of
      cytogenetical, molecular-biological, cytological and biochemical manifestations
      untypical for normal cells. The state is controlled by the mechanisms of
      regulation of checkpoints of cell cycle, and apoptosis, that is under gene p53
      control. The proof has been found that this state transfers from irradiated
      maternal cells to their surviving progeny by the epigenetical mechanisms and
      would exist until the cells restore the original state of response on the DNA
      damage. From the point of view of the genome instability conception, that
      considers the chromatine rearrangement as the adaptive-evolution mechanism of
      adaptation of the species to changeable environmental conditions, the radiation
      induced genome instability may be considered as transition of irradiated progeny
      to the state of read these to adaptation changes with two alternative pathways.
      The first leads to adaptation to enviromental conditions and restoring of normal
      cell functions. The second presents the cell transition into the transformed
      state with remain genome instability and with increase of tumour growth
      probability.

PMID- 11458642
TI  - [Biological effectiveness of pulsed and continuous neutron radiation for
      Saccharomyces yeast cells].
AB  - The article presents the data on biological effectiveness of neutrons generated
      by the pulsed reactor BARS-6 (dose-rate up to 6 x 10(6) Gy/s) in comparison with
      fast neutrons of the reactor BR-10 (dose-rate 6.3 x 10(-2) Gy/s). It was shown
      for yeast cells of a wild type that the RBE values of pulsed neutrons varied
      insignificantly with a dose (2.0-1.7) white for continuous neutron irradiation
      clear RBE dependence on the dose was observed. It was also found that the yeast
      cells had identical capability of postirradiation recovery in non-nutrient medium
      (LHR) following both gamma-irradiation and neutron exposure irrespective of
      neutron dose-rate.

PMID- 11458643
TI  - [Count, proliferation and differentiation potential of hematopoietic stem cells
      chronically exposed to radiation].
AB  - The paper presents the results of experimental studies on the kinetics and
      proliferative potential of hemopoietic stem cells in CBA-line mice under the
      conditions of chronic gamma-exposure at a dose rate of 0.16 Gy/day until the
      cumulative dose of 43.2 Gy was reached. It was possible based on the exo
      colonization test to trace the status of the stem pool in the bone marrow and
      spleen. The study included an assessment of the proliferative and differentiating
      potentials of CFUs in the hemopoiesis components of interest. The observations
      conducted at late times of chronic radiation exposure (at days 180-270) allowed
      to identify a new status of the hemopoietic system which is characterized by
      activation of CFUs proliferation and redistribution of cell subpopulations at
      differentiation stage.

PMID- 11458644
TI  - [Use of parameters of the lipid peroxidation-regulating system for assessing the
      biological consequences of the combined effect of Tween-80 and low-dose X-rays].
AB  - The effect of surfactant Tween 80 on the intensity of lipid peroxidation (LPO),
      the antioxidant status of liver and the DNA content in blood plasma of mice was
      studied. The surfactant was administered in a dose of 30 mg/kg before of after
      exposure of animals to X-rays (a dose of 16 cGy). It was found that the combined
      effect of Tween 80 and the low dose of X-rays caused disturbances in LPO
      regulatory system. Manifestation of the disturbances depended on the time
      interval after exposure, the fact whether Tween 80 was administered before or
      after irradiation, the examined tissue and the parameter studied. The
      administration of Tween 80 after irradiation intensified the effect of X-rays in
      more extent than its administration before irradiation.

PMID- 11458645
TI  - [Pharmacologic analysis of the radiation-protecting effect of indraline].
AB  - In comparative studies of the influence of selective alpha 1-adrenoblockager
      prazosine on radioprotective effect of indraline and mesotone it was found that
      the mechanism for their radioprotective effect was completely realized via alpha
      1-adrenergic action. Calcium blockager nifedipine did not block the indraline
      effect. It was discussed the issue of classifying of indraline as alpha 1B
      adrenomimetic.

PMID- 11458646
TI  - [Comparative study of the radiation-protective effectiveness of low doses of
      cysteamine, heparin, and naphtizine in experiments on mice].
AB  - Experiments were conducted on adult random-bred mice. The animals were exposed to
      a total single gamma-irradiation with a dose of 7.0 Gy (LD90/30). Drugs were
      administered prophylactically in a wide range of single doses: cystamin from
      0.015 to 150 mg/kg, naphtizin from 0.001 to 10 mg/kg, heparin from 0.025 to 500
      units/kg. It was found that the dose-effect curve based on the survival
      parameters of irradiated animals had two-phase character for cystamin and heparin
      with maxima of efficiency in the field of low and standard dosage of
      radioprotectors. Antiradiation effect of naphtizin reached maximum at low
      concentrations and then went on a plateau at usual radioprotective doses.

PMID- 11458647
TI  - [Basic results of work on ameliorating the consequences of the accident at the
      Chernobyl Atomic Energy Station in the area of agricultural radioecology druing
      the period 1986-2001 (on the 15th anniversary of the accident)].
AB  - The review has summarized the main results of the amelioration work after the
      Chernobyl accident in the field of agricultural industry. Regularities of
      radionuclide behaviour in agrosystems and effectiveness of the protection in
      agriculture were considered. The tasks of cleaning-up radioactive contamination
      in the distant periods after the accident were discussed.

PMID- 11458648
TI  - [Functional-ecological and age-specific regularities in radionuclide
      concentration in freshwater molluscs from the Chernobyl Atomic Energy Station
      exclusion zone].
AB  - The results of the studies on 90Sr and 137Cs content in the tissues of bivalve
      and gastropod mollusks of water basins in the exclusion zone of the Chernobyl NPP
      have been analyzed. The dependence of radionuclide accumulation factors on the
      peculiarities of morphological structure, functional ecology and nutrition type
      was found. The age dynamics of 137Cs content in some species of Gastropoda was
      studied.

PMID- 11458649
TI  - Radioecology: trends and future in the light of societal changes.
AB  - Radioecology is an unusual scientific discipline, in that there do not exist
      radioecologists, but that there exists a research domain with well-defined
      objectives! The science of Radioecology is per definition "multidisciplinary".
      The science of radioecology has a number of important objectives relevant to the
      radioactive contamination of the environment. A prime objective of radioecology
      is to understand how the interaction between radionuclides and the environment
      affects radiation dose. Such an understanding then permits a second major
      objective of radioecology, which is to provide suitable rehabilitation
      methodology to reduce radiation dose so that it is possible to restore the
      ecological and economic value of contaminated land.

PMID- 11458650
TI  - [Modeling the behavior of 137Cs in a soil-plant system after use of
      ameliorators].
AB  - The main processes and mechanisms responsible for 137Cs behaviour in the soil
      forest plants system following the application of ameliorants are described.
      Mathematical models are presented based on the identification of mechanisms
      governing the physico-chemical and biological processes, a set of which
      determined the radionuclides uptake by plants. The models parameterization is
      exemplified by forest soils subjected to radioactive contamination after the
      Chernobyl accident. Effects of ameliorants and time of their application on 137Cs
      behaviour in the soil-plant system are assessed. The contribution of soil
      chemical and biological processes to the decrease in the radionuclide uptake by
      plants is estimated.

PMID- 11458651
TI  - [Numerical study of parameters of action of electromagnetic pulses generated by
      electrodischarge devices on biological objects].
AB  - The calculation results of parameters of the effect of electromagnetic pulses
      generated by electrodischarge units on experimental animals (rats) are presented.
      The same results for humans as well as characteristics of electromagnetic fields
      measured at the operators working areas are also presented. The models of the
      objects are cylinders of different size. The calculations are performed by using
      the FDTD (finite-difference time-domain) technique.

PMID- 11458652
TI  - A multiple imputation approach to linear regression with clustered censored data.
AB  - We extend Wei and Tanner's (1991) multiple imputation approach in semi-parametric
      linear regression for univariate censored data to clustered censored data. The
      main idea is to iterate the following two steps: 1) using the data augmentation
      to impute for censored failure times; 2) fitting a linear model with imputed
      complete data, which takes into consideration of clustering among failure times.
      In particular, we propose using the generalized estimating equations (GEE) or a
      linear mixed-effects model to implement the second step. Through simulation
      studies our proposal compares favorably to the independence approach (Lee et al.,
      1993), which ignores the within-cluster correlation in estimating the regression
      coefficient. Our proposal is easy to implement by using existing softwares.

PMID- 11458653
TI  - Using auxiliary time-dependent covariates to recover information in nonparametric
      testing with censored data.
AB  - Murray and Tsiatis (1996) described a weighted survival estimate that
      incorporates prognostic time-dependent covariate information to increase the
      efficiency of estimation. We propose a test statistic based on the statistic of
      Pepe and Fleming (1989, 1991) that incorporates these weighted survival
      estimates. As in Pepe and Fleming, the test is an integrated weighted difference
      of two estimated survival curves. This test has been shown to be effective at
      detecting survival differences in crossing hazards settings where the logrank
      test performs poorly. This method uses stratified longitudinal covariate
      information to get more precise estimates of the underlying survival curves when
      there is censored information and this leads to more powerful tests. Another
      important feature of the test is that it remains valid when informative censoring
      is captured by the incorporated covariate. In this case, the Pepe-Fleming
      statistic is known to be biased and should not be used. These methods could be
      useful in clinical trials with heavy censoring that include collection over time
      of covariates, such as laboratory measurements, that are prognostic of subsequent
      survival or capture information related to censoring.

PMID- 11458654
TI  - Diagnostic plots for assessing the frailty distribution in multivariate survival
      data.
AB  - In biomedical studies, frailty models are commonly used in analyzing multivariate
      survival data, where the objective of the study is to estimate both the covariate
      effect and the dependence between the multivariate survival times. However,
      inference based on these models are dependent on the distributional assumption of
      frailty. We propose a diagnostic plot for assessing the frailty assumption. The
      proposed method is based on the cross-ratio function and the diagnostic plot
      suggested by Oakes (1989). We use kernel regression smoothing with bandwidth
      choice by cross-validation, to obtain the proposed plot. The resulting plot is
      capable of differentiating between the gamma and positive stable frailty models
      when strong association is present. We illustrate the feasibility of our method
      using simulation studies under known frailty distributions. The approach is
      applied to data on blindness for each eye of diabetic patients with adult onset
      diabetes and a reasonable fit to the gamma frailty model is found.

PMID- 11458655
TI  - Omnibus tests of the martingale assumption in the analysis of recurrent failure
      time data.
AB  - The Andersen-Gill multiplicative intensity (MI) model is well-suited to the
      analysis of recurrent failure time data. The fundamental assumption of the MI
      model is that the process Mi(t) for subjects i = 1, ..., n, defined to be the
      difference between a subject's counting process and compensator, i.e., Ni(t) -
      Ai(t); t > 0, is a martingale with respect to some filtration. We propose omnibus
      procedures for testing this assumption. The methods are based on transformations
      of the estimated martingale residual process Mi(t) a function of consistent
      estimates of the log-intensity ratios and the baseline cumulative hazard. Under a
      correctly specified model, the expected value of Mi(t) is approximately equal to
      zero with approximately uncorrelated increments. These properties are exploited
      in the proposed testing procedures. We examine the effects of censoring and
      covariate effects on the operating characteristics of the proposed methods via
      simulation. The procedures are most sensitive to the omission of a time-varying
      continuous covariate. We illustrate use of the methods in an analysis of data
      from a clinical trial involving patients with chronic granulatomous disease.

PMID- 11458656
TI  - Statistical analysis of marginal count failure data.
AB  - Manufacturers want to assess the quality and reliability of their products.
      Specifically, they want to know the exact number of failures from the sales
      transacted during a particular month. Information available today is sometimes
      incomplete as many companies analyze their failure data simply comparing sales
      for a total month from a particular department with the total number of claims
      registered for that given month. This information--called marginal count data-
      is, thus, incomplete as it does not give the exact number of failures of the
      specific products that were sold in a particular month. In this paper we discuss
      nonparametric estimation of the mean numbers of failures for repairable products
      and the failure probabilities for nonrepairable products. We present a
      nonhomogeneous Poisson process model for repairable products and a multinomial
      model and its Poisson approximation for nonrepairable products. A numerical
      example is given and a simulation is carried out to evaluate the proposed methods
      of estimating failure probabilities under a number of possible situations.

PMID- 11458657
TI  - Inference for reliability and stress-strength for a scaled Burr type X
      distribution.
AB  - Inference for R = P(Y < X) is considered when X and Y are independently
      distributed as scaled Burr type X random variables. Under this model, exact
      inference procedures for R cannot be found. Hence, based on the expected Fisher
      information matrix which is derived here, asymptotic inference procedures for R
      and other general functions of the parameters are developed. A bootstrap method
      to estimate variance for the maximum likelihood estimators is also discussed. To
      illustrate these techniques, an example using carbon fiber strength data is
      given. Simulations to assess the effectiveness of these techniques, as well as
      other concerns, are presented.

PMID- 11458658
TI  - Psychoanalytic psychotherapy: the enduring legacy of psychoanalysis.

PMID- 11458659
TI  - Psychoanalysis--a contextual psychology: essay in memory of Merton M. Gill.

PMID- 11458660
TI  - Fertility in the transference: analytic collaboration and reproductive conflicts.

PMID- 11458661
TI  - A case of (mis)taken identity? II: Freudian language in the ego and the id.

PMID- 11458662
TI  - On the (presumed) authority of interpretations.

PMID- 11458663
TI  - Civilization and its discontents: an ongoing update. Part 1: The death penalty.

PMID- 11458664
TI  - On presenting one's case: embraced trauma and the dialogue between analysts.

PMID- 11458665
TI  - Management of ingested foreign bodies in children.
AB  - This paper reviews the presentation, diagnosis, and management of ingested
      foreign bodies in children. It may help primary care physicians to recognize the
      wide spectrum of presentations of ingested foreign bodies in children, therefore
      emphasizing considering ingested foreign bodies in the differential diagnosis of
      many respiratory and vague gastrointestinal complaints. It also proposes an
      approach to handling asymptomatic children with foreign body ingestion and points
      out certain types of foreign bodies that require special consideration.

PMID- 11458666
TI  - Child abuse and neglect: a public health perspective.
AB  - Child abuse and neglect prevention are now poised at the threshold of the public
      health arena just as the prevention of communicable diseases and unintentional
      injuries once stood. The principles of public health combined with epidemiology
      helped eradicate smallpox. The expertise of many disciplines and the three
      pronged (primary, secondary, and tertiary) prevention approach have moved the
      concept of unintentional injuries from "accidents will happen" to predictable
      and, therefore, preventable. Child abuse and neglect are now seen as epidemic in
      society. Through surveillance, intervention, prevention, and policy changes, the
      rate of child abuse and neglect can be significantly impacted in the same way
      that rates of unintentional injuries and communicable diseases have been reduced.

PMID- 11458667
TI  - The prevention of traffic deaths and injuries: the role of physicians.

PMID- 11458668
TI  - Fathers are critical to child well-being.

PMID- 11458669
TI  - Mechanisms determining sensitivity of baroreceptor afferents in health and
      disease.
AB  - Baroreceptors sense and signal the central nervous system of changes in arterial
      pressure through a series of sensory processes. An increase in arterial pressure
      causes vascular distension and baroreceptor deformation, the magnitude of which
      depends on the mechanical viscoelastic properties of the vessel wall. Classic
      methods (e.g., isolated carotid sinus preparation) and new approaches, including
      studies of isolated baroreceptor neurons in culture, gene transfer using viral
      vectors, and genetically modified mice have been used to define the cellular and
      molecular mechanisms that determine baroreceptor sensitivity. Deformation
      depolarizes the nerve endings by opening a new class of mechanosensitive Ion
      channel. This depolarization triggers action potential discharge through opening
      of voltage-dependent sodium (Na+) and potassium (K+) channels at the "spike
      initiating zone" (SIZ) near the sensory terminals. The resulting baroreceptor
      activity and its sensitivity to changes in pressure are modulated through a
      variety of mechanisms that influence these sensory processes. Modulation of
      voltage-dependent Na+ and K+ channels and the Na+ pump at the SIZ by membrance
      potential, action potential discharge, and chemical autocrine and paracrine
      factors are important mechanisms contributing to changes in baroreceptor
      sensitivity during sustained increases in arterial pressure and in pathological
      states associated with endothelial dysfunction, oxidative stress, and platelet
      activation.

PMID- 11458670
TI  - Nicotinic acetylcholine receptors on vagal afferent neurons.
AB  - Nicotinic acetylcholine receptors (nAChRs) play an important role in various
      processes involved in regulating systemic blood pressure. These receptors are
      expressed at excitatory cholinergic synapses between sympathetic preganglionic
      neurons and postganglionic sympathetic neurons and link the integrative
      activities of the CNS with peripheral effector mechanisms of the sympathetic
      nervous system. Nicotinic AChRs are also expressed on a subset of vagal afferent
      neurons, including those involved in baroreceptor reflexes. This review discusses
      the developmental expression of nAChRs on vagal afferent neurons and two factors
      that influence the differentiation of these neurons: ganglionic satellite cells
      and neurotrophins. In addition, this review discusses two important properties of
      neuronal nAChRs: inward rectification and calcium permeability. At the molecular
      level, intracellular polyamines, acting as gating particles, effectively block
      the receptor pore in a voltage-dependent manner, producing inward rectification.
      Moreover, a critical structural determinant underlies both the block by
      intracellular polyamines and calcium permeability. Finally, this review discusses
      the modulation and block of neuronal nAChRs by extracellular polyamines and the
      possible implications for neurodegenerative diseases.

PMID- 11458671
TI  - Cellular mechanisms regulating synaptic vesicle exocytosis and endocytosis in
      aortic baroreceptor neurons.
AB  - The purpose of this chapter is to review some of the recent progress in the
      understanding of the cellular and biophysical mechanisms that are involved in the
      regulation of arterial baroreceptor neurotransmission. Synaptic depression or
      fatigue following repeated neuronal stimulation has been shown at central
      baroreceptor synapses in vivo and in vitro. As most of the central neurons have a
      limited number of vesicles, vesicle retrieval or endocytosis following exocytosis
      is thought to play a major role in preserving synaptic transmission. We have
      hypothesized that central baroreceptor terminals may inhibit their own synaptic
      transmission via feedback activation of presynaptic metabotropic glutamate
      receptors (mGluRs). We have analyzed the effects of mGluR autoreceptors (group
      III mGluRs) on voltage-gated calcium channels using standard patch-clamp
      techniques and on the process of exocytosis and endocytosis in aortic
      baroreceptor neurons using the quantitative imaging dye FM1-43 and FM2-10. Usng
      the whole-cell patch-clamp technique, we have found that activation of group III
      mGluRs with L-AP4 inhibits peak calcium channel current. Furthermore, activation
      of group III mGluRs with L-AP4 markedly decreases stimulation-induced exocytosis
      in aortic baroreceptor neurons, as measured with FM1-43, and inhibits synapsin I
      phosphorylation. These results suggest that activation of group III mGluRs may
      inhibit synaptic transmission by (1) inhibiting calcium influx, (2) decreasing
      synaptic vesicle exocytosis, and (3) modulating the mechanisms governing synaptic
      vesicle recovery and endocytosis. These effects of mGluRs on baroreceptor
      synaptic vesicles may contribute to the baroreceptor/nucleus tractus solitarius
      synaptic depression observed in vivo.

PMID- 11458672
TI  - Cellular mechanisms of baroreceptor integration at the nucleus tractus
      solitarius.
AB  - The autonomic nervous system makes important contributions to the homeostatic
      regulation of the heart and blood vessels through arterial baroreflexes, and yet
      our understanding of the central nervous system mechanisms is limited. The
      sensory synapse of baroreceptors in the nucleus tractus solitarius (NTS) is
      unique because its participation is obligatory in the baroreflex. Here we
      describe experiments targeting this synapse to provide greater understanding of
      the cellular mechanisms at the earliest stages of the baroreflex. Our approach
      utilizes electrophysiology, pharmacology, and anatomical tracers to identify and
      evaluate key elements of the sensory information processing in NTS.

PMID- 11458673
TI  - Properties of NTS neurons receiving input from barosensitive receptors.
AB  - Afferent input from barosensitive receptors, including carotid baroreceptors and
      cardiac mechanoreceptors, has been found to produce different types of discharge
      patterns in neurons in the nucleus tractus solitarius (NTS). The discharge
      patterns of the neurons may be dependent on many factors, including input from
      the different barosensitive receptor subtypes, the contribution of different
      ionotropic glutamate receptors [NMDA (N-methyl-D-aspartate) versus nonNMDA
      receptors] in transmission of the input, effects of different neuropeptide
      neurotransmitters/neuromodulators on afferent transmission, or the order of the
      neuron within the barosensitive reflex arc. It is not clear if the roles of the
      glutamate receptor subtypes are the same for neurons activated by the different
      barosensitive inputs. In addition, the amount of afferent input from the
      barosensitive receptors, due to increases or decreases in stimulating pressures,
      may result in altering the roles of the ionotropic glutamate receptor subtypes.
      While most evidence suggests that nonNMDA receptors play the greatest role in the
      transmission of afferent activity to second-orders NTS neurons, it is possible
      that increases in afferent input may lead to an enhanced role for NMDA receptors
      in the transmission of the barosensitive input, since increased depolarization of
      the NTS neurons may lead to removal of a Mg2+ block of the NMDA channel.
      Transmission of baroreceptor input at third- and higher-order neurons has been
      found to involve both nonNMDA and NMDA receptors, suggesting a possible
      functional role for the distribution of these receptor types. The roles of these
      different factors in the initiation of NTS neuronal discharge will be discussed.

PMID- 11458674
TI  - Response properties of baroreceptive NTS neurons.
AB  - Neurons in the nucleus of the solitary tract (NTS) responding to activation of
      arterial baroreceptors were recorded intracellularly using patch pipettes in an
      in situ arterially perfused working heart-brain stem preparation of rat. Seven of
      15 (i.e., 46%) of NTS neurons showed adaptive (nonlinear) excitatory synaptic
      response patterns during baroreceptor stimulation followed by an "evoked
      hyperpolarization." This evoked hyperpolarization was stimulus intensity
      dependent and capable of shunting out a subsequent baroreceptor input. We suggest
      that this adaptive response behavior may be mediated, in part, by calcium
      dependent potassium currents (IKCa) since neurons showed spike frequency
      adaptation during step depolarizations and an after-hyperpolarization after
      repetitive firing. Furthermore, in in vivo anesthetized rats, NTS microinjections
      of either charybdotoxin (225 fmol) or apamin (4.5 pmol) to block IKCa increased
      the baroreceptor reflex gain. Our data purport that the responsiveness of
      baroreceptive NTS neurons can be regulated by intrinsic membrane conductances
      such as IKCa. Modulation of such conductances during either physiological
      (exercise) or pathophysiological (essential hypertension) conditions may lead to
      changes in both the operating point and gain of the baroreceptor reflex.

PMID- 11458675
TI  - Nitroxidergic influences on cardiovascular control by NTS: a link with glutamate.
AB  - Glutamate (GLU) receptor activation, which is important in cardiovascular reflex
      transmission through the nucleus tractus solitarii (NTS), leads to release of
      nitric oxide (NO.) from central nitroxidergic neurons. Therefore, we hypothesized
      that GLU and NO. are linked in cardiovascular control by NTS. We first sought to
      determine if NO. released into NTS led to cardiovascular changes like those
      produced by GLU and found that the nitrosothiol S-nitrosocysteine, but not NO.
      itself or other NO. donors, elicited such responses in anesthetized rats. The
      responses were dependent on activation of soluble guanylate cyclase but, not
      being affected by a scavenger of NO., likely did not depend on release of NO.
      into the extracellular space. Responses to ionotropic GLU agonists in NTS, like
      those to S-nitrosocysteine, were inhibited by inhibition of soluble guanylate
      cyclase. Inhibition of neuronal NO. synthase (nNOS) also inhibited responses to
      ionotropic GLU agonists. The apparent physiologic link between GLU and NO.
      mechanisms in NTS was further supported by anatomical studies that demonstrated
      frequent association between GLU-containing nerve terminals and neurons
      containing nNOS. Furthermore, GLU receptors were often found on NTS neurons that
      were immunoreactive for nNOS. The anatomical relationships between GLU and nNOS
      and GLU receptors and nNOS were more pronounced in some subnuclei of NTS than in
      others. While seen in subnuclei that are known to receive cardiovascular
      afferents, the association was even more prominent in subnuclei that receive
      gastrointestinal afferents. These studies support a role for nitroxidergic
      neurons in mediating cardiovascular and other visceral reflex responses that
      result from release of GLU into the NTS.

PMID- 11458676
TI  - Neurotransmission of the cardiovascular reflexes in the nucleus tractus solitarii
      of awake rats.
AB  - Chemoreflex activation with potassium cyanide (i.v.) produces pressor and
      bradycardic responses in awake rats. Microinjection of AP-5, a selective NMDA
      receptor antagonist, into the nucleus tractus solitarii (NTS) produced a dose
      dependent blockade of the bradycardic response; while microinjection of DNQX, a
      selective non-NMDA receptor antagonist, or kynurenic acid, a nonselective
      ionotropic receptor antagonist, produced only a partial reduction in the pressor
      response, indicating that the bradycardic component of the chemoreflex is
      mediated by NMDA receptors and that the sympathoexcitatory component may involve
      neurotransmitters other than excitatory amino acids. With respect to the
      baroreflex, we verified that the gain of baroreflex bradycardia in response to
      phenyleprine (Phe) infusion was significantly reduced in a dose-dependent manner
      by microinjection of AP-5 into the NTS, indicating that the parasympathetic
      component of the baroreflex is mediated mainly by NMDA receptors. However, in a
      series of experiments involving the electrical stimulation of the aortic
      depressor nerve (ADN) we observed that the maximal bradycardic response was
      almost blocked by the combination of microinjection of NMDA and non-NMDA receptor
      antagonists into the NTS, while the depressor response was only partially
      reduced. These data indicate that the bradycardic response produced by the
      activation of the baroreflex with Phe is mediated by mechanisms differing from
      those in response to the electrical stimulation of the ADN because phenylephrine
      also activates carotid and aortic baroreceptors, while unilateral electrical
      stimulation of the ADN involves only one specific set of baroreceptor afferents.
      These data also indicate that the sympatho inhibitory component of this response
      may involve neurotransmitters other than L-glutamate. We discuss the possibility
      that two different afferent systems of arterial baroreceptors are involved in the
      modulation of parasympathoexcitation and sympathoinhibition: one activated within
      the normal range of pulsatile arterial pressure (on a pulse-to-pulse basis) and
      the other acting under circumstances of challenge to the pulsatile arterial
      pressure above the normal range.

PMID- 11458677
TI  - Adenovirus-mediated gene transfer into the NTS in conscious rats. A new approach
      to examining the central control of cardiovascular regulation.
AB  - The nucleus tractus solitarii (NTS) is an important site for the regulation of
      sympathetic nerve activity. It receives the signals through afferent fibers from
      arterial baroreceptors, chemoreceptors, cardiopulmonary receptors, and other
      visceral receptors. Many studies have examined the role of nitric oxide (NO) in
      the NTS in cardiovascular regulation. However, most of these studies were
      conducted in an acute state with anesthesia. We have developed a novel technique
      of endothelial nitric oxide synthase (eNOS) gene transfer into the NTS in vivo.
      Adenovirus vectors encoding either the beta-galactosidase gene (Ad beta gal) or
      the endothelial nitric oxide synthase gene (AdeNOS) gene were transfected into
      the NTS. In the Ad beta gal-treated rats, the local expression of beta
      galactosidase was confirmed by X-Gal staining, and beta-galactosidase activity
      was quantified using a colorimetric assay. In the AdeNOS-treated rats, the local
      expression of eNOS protein was confirmed by immunohistochemistry, and eNOS
      production was measured by in vivo microdialysis. Blood pressure and heart rate
      were monitored by a radiotelemetry system in a conscious state. The expression of
      each gene was observed from day 5 to day 10 after the gene transfer. In the
      AdeNOS-treated rats, blood pressure and heart rate significantly decreased from
      day 5 to day 10, and then thereafter gradually recovered over time. Our method
      may be useful in examining the local effect of a particular substance produced by
      a specific gene in the brain on cardiovascular function.

PMID- 11458678
TI  - Arterial baroreceptors and experimental diabetes.
AB  - Alterations of the autonomic reflex control of the cardiovasclar system have been
      demonstrated in clinical and animal models of insulin-dependent diabetes
      mellitus. Established neuroaxonal dystrophy is considered the neuropathological
      hallmark of chronic experimental diabetes. However, the afferent arm of the
      arterial baroreflex, that is, the carotid sinus nerve and the aortic depressor
      nerve, has received much less attention in studies dealing with this
      physiopathological model. The attenuation of the pressure response to bilateral
      carotid occlusion in conscious rats indicates a derangement of the baroreflex,
      probably involving an alteration of the carotid sinus nerve. There is
      histological evidence obtained from adult spontaneous insulin-dependent diabetic
      rats (strain BB/S) of a carotid sinus nerve with signs of axonal swelling and
      intramyelinic edema, suggesting diabetic neuropathy. The study of aortic
      baroreceptor activity in anesthetized rats with short- and long-term
      streptozotocin diabetes by means of cross-spectral analysis of baroreceptor
      activity versus arterial pressure revealed a dysfunction in the afferent arm of
      the baroreflex even during a short period of diabetes. The morphology of the
      aortic depressor nerve of streptozotocin-diabetic rats indicated axonal atrophy
      by visual analysis remarkably at the distal segments of the nerves. This finding
      was confirmed by morphometric study of the myelinated fibers. In conclusion,
      although studies of the arterial baroreceptors related to experimental diabetes
      are scanty in the literature, there is electrophysiological and histological
      evidence demonstrating that the carotid sinus and the aortic depressor nerves are
      abnormal in this experimental model.

PMID- 11458679
TI  - Oxytocin in the NTS. A new modulator of cardiovascular control during exercise.
AB  - The role of brain stem oxytocinergic projections in the modulation of heart rate
      control during exercise is discussed on the basis of both changes in endogenous
      peptide content and heart rate changes observed during exercise. Running on a
      treadmill caused an increase in oxytocin content in dorsal/ventral brain stem
      areas and spinal cord, specifically in trained rats. Trained rats pretreated with
      a specific oxytocin receptor antagonist into the dorsal brain stem area
      (corresponding to the nucleus tractus solitarii and dorsal motor nucleus of the
      vagus, or NTS/DMV) showed a significant potentiation of exercise tachycardia with
      no change in the blood pressure response. The same treatment in sedentary rats
      was without effect. On the other hand, administration of exogenous oxytocin into
      this area caused significant blunting of exercise tachycardia in both groups,
      with no change in the pressure response. It is proposed that long-descending
      oxytocinergic pathways from the hypothalamus to the NTS/DMV area serve as a link
      between the two main neural controllers of the circulation--that is, the central
      command and feedback control mechanisms driven by the peripheral receptor
      signals. Our results strongly suggest that oxytocinergic input to NTS/DMV, by
      restraining the tachycardic response of trained individuals, contributes to the
      smaller response observed after training, without compromising cardiac output
      adjustment and the circulatory demand during exercise.

PMID- 11458680
TI  - Exercise and sensory integration. Role of the nucleus tractus solitarius.
AB  - Since NTS neurons receive synaptic input from many sensory modalities, it is
      crucial to understand the neuronal mechanisms involved in synaptic processing. We
      have proposed that GABA-containing neurons in the NTS are the primary target for
      somatic afferent fibers activated by skeletal muscle contraction. In our model,
      local inhibition of baroreceptor signaling is necessary to counteract the
      increase in baroreceptor input such that NTS output is normalized and baroreflex
      sensitivity is maintained during exercise. This GABAergic mechanism, in
      conjunction with sympathoexcitation evoked by somatic afferents, preserves reflex
      sensitivity and resets the baroreflex, respectively. Unfortunately, there is
      insufficient data to date to support or refute the proposed role for GABA on
      baroreflex function during exercise. However, we feel that this model will be
      useful in formulating future experiments to explore these synaptic interactions.

PMID- 11458681
TI  - Synaptic and neurotransmitter activation of cardiac vagal neurons in the nucleus
      ambiguus.
AB  - Cardiac vagal neurons play a critical role in the control of heart rate and
      cardiac function. These neurons, which are primarily located in the nucleus
      ambiguus (NA) and the dorsal motor nucleus of the vagus (DMNX), dominate the
      neural control of heart rate under normal conditions. Cardiac vagal activity is
      diminished and unresponsive in many disease states, while restoration of
      parasympathetic activity to the heart lessens ischemia and arrhythmias and
      decreases the risk of sudden death. Recent work has demonstrated that cardiac
      vagal neurons are intrinsically silent and therefore rely on synaptic input to
      control their firing. To date, three major synaptic inputs to cardiac vagal
      neurons have been identified. Stimulation of the nucleus tractus solitarius
      evokes a glutamatergic pathway that activates both NMDA and non-NMDA
      glutamatergic postsynaptic currents in cardiac vagal neurons. Acetylcholine
      excites cardiac vagal neurons via three mechanisms, activating a direct ligand
      gated postsynaptic nicotinic receptor, enhancing postsynaptic non-NMDA currents,
      and presynaptically by facilitating transmitter release. This enhancement by
      nicotine is dependent upon activation of pre- and postsynaptic P-type voltage
      gated calcium channels. Additionally, there is a GABAergic innervation of cardiac
      vagal neurons. The transsynaptic pseudorabies virus that expresses GFP (PRV-GFP)
      has been used to identify, for subsequent electrophysiologic study, neurons that
      project to cardiac vagal neurons. Bartha PRV-GFP-labeled neurons retain their
      normal electrophysiological properties, and the labeled baroreflex pathways that
      control heart rate are unaltered by the virus.

PMID- 11458682
TI  - Excitatory inputs to the RVLM in the context of the baroreceptor reflex.
AB  - The central neural circuit mediating baroreceptor control of sympathetic
      vasomotor outflow involves an excitatory projection from arterial baroreceptors
      to nucleus tractus solitarius, an excitatory projection from nucleus tractus
      solitarius to the caudal ventrolateral medulla, an inhibitory projection from the
      caudal ventrolateral medulla to the rostral ventrolateral medulla (RVLM), and an
      excitatory projection from the RVLM to sympathetic preganglionic neurons in the
      spinal cord. For this circuit to be operational, the relevant neurons in the RVLM
      must be tonically active. Indeed, numerous studies have demonstrated that RVLM
      vasomotor neurons are tonically active; however, little is known regarding the
      nature of the tonic excitatory drive to these neurons. We present a model in
      which RVLM vasomotor neurons are tonically excited by inputs to the RVLM that can
      be blocked by the excitatory amino acid receptor antagonist, kynurenic acid, as
      well as an input from the caudal ventrolateral medulla that is not sensitive to
      kynurenic acid.

PMID- 11458683
TI  - Regulation of sympathetic tone and arterial pressure by the rostral ventrolateral
      medulla after depletion of C1 cells in rats.
AB  - This review describes experiments designed to determine the role of bulbospinal
      (BS) C1 cells in regulating the sympathetic outflow and blood pressure. This goal
      was achieved by analyzing the physiological consequences of destroying BS C1
      cells. These cells were destroyed by suicide transport of an anti-dopamine-beta
      hydroxylase antibody conjugated to saporin (anti-D beta H-SAP). Two to 3 weeks
      after spinal cord injection (T2-T6), the toxin destroyed 75-85% of BS C1 and C3
      cells along with > 95% of BS noradrenergic neurons (A5, A6, A7). The toxin spared
      BS noncatecholaminergic cells. Under anesthesia, toxin-treated rats had a normal
      blood pressure and an apparently normal sympathetic nerve discharge (SNA,
      splanchnic), and intravenous clonidine caused a normal degree of
      sympathoinhibition. Inhibition of rostral ventrolateral medulla (RVLM) neurons by
      bilateral injection of muscimol caused the same hypotension and
      sympathoinhibition as in control rats. The baroreflex range was 41% attenuated by
      the toxin, but the MAP50 was unchanged. Sympathoexcitatory responses to
      stimulation of peripheral chemoreceptors with cyanide or to electrical
      stimulation of RVLM were severely depressed (60% to 80%) in toxin-treated rats.
      Rats in which A5 neurons were selectively destroyed had no deficit in the
      parameters tested. Unit recordings of BS RVLM neurons indicated that the toxin
      destroyed most barosensitive C1 neurons, but spared noncatecholaminergic lightly
      myelinated BS cells. In summary, the integrity of C1 neurons is not essential for
      the generation of SNA and the maintenance of BP under resting conditions, perhaps
      because these functions are performed primarily by noncatecholaminergic BS
      neurons. However, the deficits caused by treatment with anti-D beta H-SAP
      indicate that BS C1 neurons play a crucial role in several sympathoexcitatory
      responses mediated by the RVLM.

PMID- 11458684
TI  - The role of the medullary lateral tegmental field in the generation and
      baroreceptor reflex control of sympathetic nerve discharge in the cat.
AB  - Data from experiments with single neuron recordings as well as central
      microinjections of N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino
      receptor antagonists that have led to a model of central sympathetic pathways
      that includes synaptic relays in the medullary lateral tegmental field (LTF) of
      the cat are summarized. Evidence is presented that (1) the LTF contains a
      population of tonically active sympathoexcitatory neurons that drive rostral
      ventrolateral medullary neurons, (2) blockade of non-NMDA receptors in the LTF
      significantly reduces basal levels of sympathetic nerve discharge (SND) and mean
      arterial pressure in baroreceptor-denervated cats, and (3) blockade of NMDA
      mediated neurotransmission in the LTF prevents baroreceptor reflex control of
      SND. Thus, LTF neurons play an important role in the generation and baroreceptor
      reflex control of SND in the cat.

PMID- 11458685
TI  - Degenerins. At the core of the metazoan mechanotransducer?
AB  - Mechanosensory signaling, believed to be mediated by mechanically gated ion
      channels, constitutes the basis for the senses of touch and hearing, and
      contributes fundamentally to the development and homeostasis of all organisms.
      Despite this profound importance in biology, little is known of the molecular
      identities or functional requirements of mechanically gated ion channels. Genetic
      analyses of touch sensation and locomotion in Caenorhabditis elegans have
      implicated a new class of ion channels, the degenerins (DEG) in nematode
      mechanotransduction. Related fly and vertebrate proteins, the epithelial sodium
      channel (ENaC) family, have been implicated in several important processes,
      including transduction of mechanical stimuli, pain sensation, gametogenesis,
      sodium reabsorption, and blood pressure regulation. Still-to-be-discovered
      DEG/ENaC proteins may compose the core of the elusive human mechanotransducer.

PMID- 11458686
TI  - Differential regulation of sympathetic outflows to vasoconstrictor and
      thermoregulatory effectors.
AB  - The medullary premotor neurons determining the sympathetic outflow regulating
      cardiac function and vasoconstriction are located in the rostral ventrolateral
      medulla (RVLM). The present study sought evidence for differential
      characteristics and baroreceptor reflex sensitivities between the sympathetic
      nerve activity (SNA) controlling brown adipose tissue (BAT) metabolism and
      thermogenesis and cardiovascular SNA such as that controlling mesenteric
      vasoconstriction via the splanchnic (SPL) nerve. The tonic discharge of
      sympathetic nerves is determined by the inputs to functionally specific
      sympathetic preganglionic neurons from supraspinal populations of premotor
      neurons. Under normothermic conditions, BAT SNA was nearly silent, while SPL SNA
      exhibited sustained, large-amplitude bursts. Disinhibition of neurons in the
      rostral raphe pallidus (RPa), a potential site of sympathetic premotor neurons
      controlling BAT SNA, or icv injection of prostaglandin E2, a pyrogenic stimulus,
      elicited a dramatic increase in BAT SNA. SPL SNA was strongly influenced by the
      baroreceptor reflex as indicated by a high coherence to the arterial pressure,
      while activated BAT SNA exhibited no correlation with the arterial pressure.
      Since these characteristics and reflex responses in sympathetic outflow have been
      shown to arise from the ongoing or altered discharge of sympathetic premotor
      neurons, the marked differences between SPL SNA and BAT SNA provide strong
      evidence supporting the hypothesis that vasoconstriction and thermogenesis
      (metabolism) are controlled by distinct populations of sympathetic premotor
      neurons, the former in the RVLM and strongly baroreceptor-modulated and the
      latter potentially in the RPa exhibiting little influence of baroreceptor reflex
      activation.

PMID- 11458687
TI  - Evidence for central organization of cardiovascular rhythms.
AB  - Spectral analysis of heart rate and arterial pressure variabilities is a powerful
      noninvasive tool that is increasingly used to infer alterations of cardiovascular
      autonomic regulation in a variety of physiological and pathophysiological
      conditions such as hypertension, myocardial infarction, and congestive heart
      failure. A most important methodological issue to properly interpret the results
      obtained by the spectral analysis of cardiovascular variability signals is
      represented by the attribution of neurophysiological correlates to these spectral
      components. In this regard, recent application of spectral techniques to the
      evaluation of the oscillatory properties of sympathetic efferent activity in
      animals as well as in humans offers a new approach to a better understanding of
      the relationship between cardiovascular oscillations and autonomic regulation.
      The data so far collected seem to suggest the presence of a centrally organized
      neural code, characterized by excitatory and inhibitory neural mechanisms
      subserving the genesis and the regulation of cardiovascular oscillations
      concerning the major variables of autonomic regulation.

PMID- 11458688
TI  - Heterogeneous receptor distribution in autonomic neurons.
AB  - The central nervous system components for baroreflex regulation of sympathetic
      outflow include specific sets of neurons in the brain and spinal cord. Critical
      nuclei containing sympathetic baroreceptive neurons are the nuclei of the
      solitary tract, regions of the caudal and rostral ventrolateral medulla, and the
      intermediolateral cell column in the spinal cord. While many other brain regions
      project to these nuclei, cells in these areas appear to form the minimal required
      pathway for baroreflex control of sympathetic outflow. Synaptic connections have
      been identified between cells in these nuclei that are consistent with a serial
      relay from baroreceptor afferents through the brain stem and to sympathetic
      preganglionic neurons in the spinal cord. In recent years, we have examined the
      distribution of receptor proteins in these neurons, with a focus on receptors
      that are most likely to modulate the activity of these cells. In three studies
      examining the distribution of different receptors on distinct neurons, each study
      found some type of heterogeneity in the distribution of each receptor within a
      particular type of neuron. This heterogeneity was seen with regard to the
      distribution of receptor protein within the dendritic tree of individual neurons,
      as well as between pre- and postsynaptic sites on the same cell. This
      heterogeneous distribution of receptors suggests that receptors undergo dendritic
      targeting within autonomic neurons. This receptor trafficking may be regulated by
      heterogeneous afferent input to autonomic neurons and could be changed under
      conditions where afferent activity is significantly altered.

PMID- 11458689
TI  - Integrative sympathetic baroreflex regulation of arterial pressure.
AB  - The baroreflex system is the most important negative feedback control system
      functioning physiologically to attenuate the effects of rapid perturbation in
      arterial pressure. However, the complexity of the system resulting from the
      closed-feedback loop, nonlinearity, and system memory makes detailed quantitative
      characterization of the baroreflex system difficult. To overcome such
      limitations, we proposed a framework to decompose the baroreflex loop into two
      major arcs, that is, the mechanoneural arc and neuromechanical arc. Steady state
      analysis indicated that such decomposition allowed us to analytically determine
      the operating point by equilibrating two respective function curves. Dynamic
      analysis suggested that the mechanoneural arc accelerated the slow mechanical
      response of the neuromechanical arc. The acceleration mechanism in the
      mechanoneural are optimized arterial pressure regulation in achieving both
      stability and quickness. Establishment of such an integrative framework allowed
      the development of an artificial feedback control system able to regulate
      sympathetic vasomotor tone.

PMID- 11458690
TI  - Central baroreflex resetting as a means of increasing and decreasing sympathetic
      outflow and arterial pressure.
AB  - The arterial baroreflex has two important functions. First, the arterial
      baroreflex is a negative feedback reflex that regulates arterial pressure around
      a preset value called a set or operating point. Second, the arterial baroreflex
      also establishes the prevailing systemic arterial pressure when the operating
      point is reset. That is, modulating the response of barosensitive neurons in the
      central nervous system (CNS) establishes the operating point or prevailing
      systemic arterial pressure. Therefore, the operating point of the arterial
      baroreflex is not fixed, but is variable over a wide range of pressures and is
      determined by a variety of inputs from the peripheral and central nervous
      systems. At the onset of dynamic exercise, heart rate (HR) and sympathetic nerve
      activity (SNA) increase abruptly and dramatically. The initial increase in HR and
      SNA is mediated by central command. Central command operates by resetting the
      operating point of the arterial baroreflex to a higher pressure. In this
      situation, the operating point of the arterial baroreflex is above the prevailing
      arterial pressure, which elicits a blood pressure error. This error is corrected
      by activating SNA and inhibiting parasympathetic nerve activity, which increases
      cardiac output and peripheral resistance and, consequently, arterial pressure.
      After exercise, loss of central command and enhanced activity of the
      cardiopulmonary reflex resets the operating point of the arterial baroreflex to a
      lower pressure. In this situation, the operating point of the arterial baroreflex
      is below the prevailing arterial pressure, which elicits a blood pressure error.
      This error is corrected by inhibiting SNA, which decreases peripheral resistance
      and consequently arterial pressure. In these situations, central resetting of the
      arterial baroreflex is a means of increasing and decreasing sympathetic outflow
      and arterial pressure.

PMID- 11458691
TI  - Effects of exercise training on baroreflex control of the cardiovascular system.
AB  - Dynamic exercise training has been recommended as an antihypertensive therapy and
      as a way to modify the effects of many cardiovascular risk factors (Arakawa,
      1993; Arroll and Beaglehole, 1992; Kelly and McClellan, 1994: see references 1-3
      in the paper). However, the mechanisms underlying the blood-pressure lowering
      effect of chronic exercise are still poorly understood. It has been suggested
      that a decrease in sympathetic tone is one of the major effects elicited by
      chronic exercise on the cardiovascular system. The importance of the sympathetic
      component is confirmed in this review, since it was found that in spontaneously
      hypertensive rats (SHR) a marked decrease in sympathetic activity occurred after
      exercise training. Moreover, our findings suggest that this effect is mediated by
      improving the depressed baroreceptor function, which is, in part, responsible for
      the attenuation of the baroreflex sensitivity observed in the sedentary SHR
      (Krieger et al., 1998, 1999; see references 4 and 5 in the paper).

PMID- 11458692
TI  - CNS effects of ovarian hormones and metabolites on neural control of circulation.
AB  - Pregnant women often experience orthostatic hypotension, and pregnancy is
      associated with increased susceptibility to hemorrhagic hypotension. Experiments
      evaluating arterial baroreflex control of efferent sympathetic nerve activity in
      virgin and term-pregnant rats revealed that arterial baroreflex
      sympathoexcitation is attenuated, while sympathoinhibitory responses are well
      maintained or potentiated. Following a hypotensive challenge, pregnant animals
      exhibit attenuated Fos expression in the rostral ventrolateral medulla (RVLM),
      suggesting that unloading of arterial baroreceptors results in less excitation of
      presympathetic neurons in the brain stem. Other experiments, in which afferent
      baroreceptor discharge was recorded, suggest that this was not due to differences
      in afferent baoreceptor function. GABAergic mechanisms are responsible for tonic
      inhibition of sympathoexcitatory neurons in the RVLM and the major metabolite of
      progesterone, 3 alpha-OH-dihydro-progesterone (3 alpha-OH-DHP), which is elevated
      in pregnancy, is the most potent endogenous positive modulator of CNS GABAA
      receptor function. Additional experiments revealed that acutely administered 3
      alpha-OH-DHP, either intravenously or directly into the RVLM, mimicked the
      effects of pregnancy on baroreflex control of efferent sympathetic nerve activity
      and potentiated pressure sensitivity of spinally projecting RVLM neurons.
      Preliminary experiments using semiquantitative RT-PCR, evaluated the relative
      expression of three subunits (alpha 1-3) of the GABAA receptor, and suggest that
      chronic exposure to elevated levels of ovarian hormones can result to changes in
      GABAA receptor subunit composition. It is likely that changes in control of
      sympathetic outflow in pregnancy are related to complex interactions between
      genomic and nongenomic actions of ovarian hormones and metabolites.

PMID- 11458693
TI  - Central angiotensin and baroreceptor control of circulation.
AB  - Angiotensin (Ang) receptors are located in many important central nuclei involved
      in the regulation of the cardiovascular system. While most interest has focused
      on forebrain circumventricular actions, areas of the brainstem such as the
      nucleus of the solitary tract and the ventrolateral medulla contain high
      concentrations of AT1 receptors. The present review encompasses the physiological
      role of Ang II in the hindbrain, particularly in relation to its influence on
      baroreflex control mechanisms. In rabbits there are sympatho-excitatory AT1
      receptors in the rostral ventrolateral medulla (RVLM), accessible to Ang II from
      the cerebrospinal fluid. Activation of these receptors acutely increases renal
      sympathetic nerve activity (RSNA) and RSNA baroreflex responses. However,
      blockade of endogenous Ang receptors in the brainstem also shows
      sympathoexcitation, suggesting there is greater endogenous activity of a
      sympathoinhibitory Ang II action. Microinjections of angiotensin antagonists into
      the RVLM showed relatively little tonic activity of endogenous Ang II influencing
      sympathetic activity in conscious rabbits. However, Ang II receptors in the RVLM
      mediate sympathetic responses to airjet stress in conscious rabbits. Similarly
      with respect to heart rate baroreflexes, there appears to be little tonic effect
      of angiotensin in the brainstem in normal conscious animals. Chronic infusion of
      Ang II for two weeks into the fourth ventricle of conscious rabbits inhibits the
      cardiac baroreflex while infusion of losartan increases the gain of the reflex.
      These actions suggest that Ang II in the brainstem modulates sympathetic
      responses depending on specific afferent and synaptic inputs in both the short
      term but importantly also in the long term, thus forming an important mechanism
      for increasing the range of adaptive response patterns.

PMID- 11458694
TI  - The interaction of angiotensin II and osmolality in the generation of sympathetic
      tone during changes in dietary salt intake. An hypothesis.
AB  - At rest, sympathetic nerves exhibit tonic activity which contributes to arterial
      pressure maintenance. Significant evidence suggests that the absolute level of
      sympathetic tone is altered in a number of physiologic and pathophysiologic
      states. However, the mechanisms by which such changes in sympathetic tone occur
      are incompletely understood. The purpose of this review is to present evidence
      that humoral factors are essential in these changes and to detail specifically an
      hypothesis for the mechanisms that underlie the changes in sympathetic tone that
      are produced during increases or decreases in dietary salt intake. It is proposed
      that the net effect of changes in dietary salt on sympathetic activity is
      determined by the balance between simultaneous and parallel sympathoinhibitory
      and sympathoexcitatory humoral mechanisms. A key element of the
      sympathoinhibitory mechanism is the chronic sympathoexcitatory effects of
      angiotensin II (ANG II). When salt intake increases, ANG II levels fall, and the
      sympathoexcitatory actions of ANG II are lost. Simultaneously, a
      sympathoexcitatory pathway is triggered, possibly via increases in osmolality
      which activate osmoreceptors or sodium receptors. In normal individuals, the
      sympathoinhibitory effects of increased salt predominate, sympathetic activity
      decreases, and arterial pressure remains normal despite salt and water retention.
      However, in subjects with salt-sensitive hypertension, it appears that the
      sympathoexcitatory effects of salt predominate, possibly due to an inability to
      adequately suppress the levels or actions of ANG II. The net result, therefore,
      is an inappropriate increase in sympathetic activity during increased dietary
      salt which may contribute to the hypertensive process.

PMID- 11458695
TI  - Peripheral and central interactions between the renin-angiotensin system and the
      renal sympathetic nerves in control of renal function.
AB  - Increases in renal sympathetic nerve activity (RSNA) regulate the functions of
      the nephron, the vasculature, and the renin-containing juxtaglomerular granular
      cells. As increased activity of the renin-angiotensin system can also influence
      nephron and vascular function, it is important to understand the interactions
      between RSNA and the renin-angiotensin system in the control of renal function.
      These interactions can be intrarenal, that is, the direct (via specific
      innervation) and indirect (via angiotensin II) contributions of increased RSNA to
      the regulation of renal function. The effects of increased RSNA on renal function
      are attenuated when the activity of the renin-angiotensin system is suppressed or
      antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type
      AT1 receptor antagonists. The effects of intrarenal administration of angiotensin
      II are attenuated following renal denervation. These interactions can also be
      extrarenal, that is, in the central nervous system, wherein RSNA and its arterial
      baroreflex control are modulated by changes in activity of the renin-angiotensin
      system. In addition to the circumventricular organs, the permeable blood-brain
      barrier of which permits interactions with circulating angiotensin II, there are
      interactions at sites behind the blood-brain barrier that depend on the influence
      of local angiotensin II. The responses to central administration of angiotensin
      II type AT1 receptor antagonists, into the ventricular system or microinjected
      into the rostral ventrolateral medulla, are modulated by changes in activity of
      the renin-angiotensin system produced by physiological changes in dietary sodium
      intake. Similar modulation is observed in pathophysiological models wherein
      activity of both the renin-angiotensin and sympathetic nervous systems is
      increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites
      of interaction between the renin-angiotensin system and RSNA are involved in
      influencing the neural control of renal function.

PMID- 11458696
TI  - Renal arterial pressure variability. A role in blood pressure control?
AB  - It is becoming generally appreciated that blood pressure (BP) fluctuations can
      have major pathophysiological importance in hypertensives. Nonetheless, little is
      known regarding the influence of short-term changes in BP on kidney function, a
      crucial control element for long-term BP regulation. This overview summarizes
      first efforts to unravel the importance of BP dynamics on renal function. It
      seems that the kidney is not only an important control element in the BP
      regulation network; the renal vascular bed may also be very susceptible to BP
      oscillations, which can occur, for example, from baroreflex malfunction.

PMID- 11458697
TI  - Rhythmicities in sympathetic discharge: a signal of cardiorespiratory integration
      in developing animals.
AB  - We have been pursuing various avenues of investigation to elucidate the postnatal
      maturation of neural regulation of cardiovascular and respiratory integration. In
      this paper we present our results from a systematic analysis of age-related
      modulations of sympathetic (SYMP) activity with respect to experimental
      alterations in baroreceptor afferent inputs. The three age groups of piglets were
      chosen based on different responses to a complex stimulus, i.e., the Valsalva
      maneuver. Postnatal maturation of SYMP activity was examined by spectral analysis
      of SYMP discharge using cross-power, full and partial coherence. Three general
      oscillations were observed in spontaneous SYMP discharges in the 0-30 Hz range.
      We divided that range into five frequency bands (0-2, 2-6, 6-12, 12-20, 20-30
      Hz), which included periodicities in phase with both central respiratory activity
      and the cardiac cycle. Spectral analyses of SYMP activity after either
      baroreceptor activation (phenylephrine) or deactivation (nitroprusside) revealed
      that respiratory modulation was age-related across all frequencies while
      baroreceptor modulation was usually age-related within three of the five
      frequency bands. These results lead to questions concerning the possible role of
      the autonomic nervous system and/or central interactions between the respiratory
      and SYMP rhythm generators in the etiology of sudden infant death syndrome
      (SIDS).

PMID- 11458698
TI  - ENaC subunits are molecular components of the arterial baroreceptor complex.
AB  - Mechanosensation is essential to the perception of our environment. It is
      required for hearing, touch, balance, proprioception, and blood pressure
      homeostasis. Yet little is known about the identity of ion-channel complexes that
      transduce mechanical stimuli into neuronal responses. Genetic studies in
      Caenorhabditis elegans suggest that members of the DEG/ENaC family may be
      mechanosensors. Therefore we tested the hypothesis that mammalian epithelial
      Na(+)-channel (ENaC) subunits contribute to the mechanosensor in baroreceptor
      neurons. The data presented here show that ENaC transcripts and proteins are
      expressed in mechanosensory neurons and at the putative sites of
      mechanotransduction in baroreceptor sensory-nerve terminals. Additionally, known
      ENaC inhibitors, amiloride and benzamil, disrupt mechanotransduction in arterial
      baroreceptor neurons. These data are consistent with the hypothesis that DEG/ENaC
      proteins are components of mechanosensitive ion-channel complexes.

PMID- 11458699
TI  - The regulation of sympathetic outflow in heart failure. The roles of angiotensin
      II, nitric oxide, and exercise training.
AB  - Sympatho-excitation is a hallmark of the chronic heart failure (CHF) state. It
      has long been assumed that this sympatho-excitation is mediated by a reduction in
      sensory input from cardiopulmonary and arterial baroreceptors. However, recent
      data suggest that these reflexes may only be important in the initiation of the
      sympatho-excitatory state and may not be necessary for the sustained increase in
      sympathetic nerve activity (SNA) in CHF. Two humoral factors that can influence
      SNA are nitric oxide (NO) and angiotensin II (AngII). Animals with CHF exhibit a
      downregulation in central gene expression for the neuronal isoform of nitric
      oxide synthase (nNOS). In addition, blockade of AngII receptors in combination
      with NO donation reduces SNA in animals with CHF, while NO donation alone has no
      effect on SNA. Chronic exercise training (EX) reduces both plasma AngII and SNA
      in rabbits with CHF while improving baroreflex function. Blockade of AT1
      receptors enhances baroreflex function in non-EX CHF rabbits, but has little
      effect in EX CHF rabbits. These data suggest that the sympatho-excitatory state
      that is typical of CHF is, in part, due to changes in AngII and NO. Depressed
      baroreflex function and the elevated SNA can be improved by EX in animals with
      CHF.

PMID- 11458700
TI  - Neurohumoral regulation in ischemia-induced heart failure. Role of the forebrain.
AB  - Congestive heart failure (CHF) is characterized by neurohumoral excitation.
      Increased sympathetic drive and activation of the reninangiotensin-aldosterone
      system (RAAS), with vasoconstriction and volume retention, are hallmarks of the
      CHF syndrome. Treatment strategies have targeted the peripheral influences of
      these two systems, but have not addressed the central mechanisms that drive them.
      We monitored the development of CHF following coronary ligation in adult Sprague
      Dawley rats. Left ventricular dysfunction characteristic of CHF was confirmed by
      echocardiography, and the CHF syndrome was validated by measurements of
      circulating hormones, sodium appetite, thirst, renal sodium and water retention,
      and renal sympathetic nerve activity (RSNA). In CHF rats, neuronal activity in
      the hypothalamic paraventricular nucleus (PVN), which mediates downstream effects
      of forebrain circumventricular organs, was increased and was inhibited by
      blocking components of the RAAS at the forebrain level. Forebrain (AV3V) lesions
      and intracarotid (forebrain directed) injections of agents (captopril, losartan,
      spironolactone) that block RAAS substantially attenuated the behavioral and
      physiological manifestations of CHF. Intravenous losartan and captopril, in doses
      that lower arterial pressure, increased RSNA. These findings demonstrate an
      important role for RAAS-activated forebrain mechanisms in CHF and suggest that
      the central neural mechanisms driving sympathetic nerve activity and volume
      retention may persist and promote the progression of CHF despite treatments
      directed toward the peripheral influences of RAAS.

PMID- 11458701
TI  - Regulation of sympathetic nervous system function after cardiovascular
      deconditioning.
AB  - Humans subjected to prolonged periods of bed rest or microgravity undergo
      deconditioning of the cardiovascular system, characterized by resting
      tachycardia, reduced exercise capability, and a predisposition for orthostatic
      intolerance. These changes in cardiovascular function are likely due to a
      combination of factors, including changes in control of body fluid balance or
      cardiac alterations resulting in inadequate maintenance of stroke volume, altered
      arterial or venous vascular function, reduced activation of cardiovascular
      hormones, and diminished autonomic reflex function. There is evidence indicating
      a role for each of these mechanisms. Diminished reflex activation of the
      sympathetic nervous system and subsequent vasoconstriction appear to play an
      important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model
      of deconditioning, evaluated the potential role of altered arterial baroreflex
      control of the sympathetic nervous system. These studies indicate that HU results
      in blunted baroreflex-mediated activation of both renal and lumbar sympathetic
      nerve activity in response to a hypotensive stimulus. HU rats are less able to
      maintain arterial pressure during hemorrhage, suggesting that diminished ability
      to increase sympathetic activity has functional consequences for the animal.
      Reflex control of vasopressin secretion appears to be enhanced following HU.
      Blunted baroreflex-mediated sympathoexcitation appears to involve altered central
      nervous system function. Baroreceptor afferent activity in response to changes in
      arterial pressure is unaltered in HU rats. However, increases in efferent
      sympathetic nerve activity for a given decrease in afferent input are blunted
      after HU. This altered central nervous system processing of baroreceptor inputs
      appears to involve an effect at the rostral ventrolateral medulla (RVLM).
      Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is
      enhanced after HU. Augmented inhibition apparently arises from sources other than
      the caudal ventrolateral medulla. If similar alterations in control of the
      sympathetic nervous system occur in humans in response to cardiovascular
      deconditioning, it is likely that they play an important role in the observed
      tendency for orthostatic intolerance. Combined with potential changes in vascular
      function, cardiac function, and hypovolemia, the predisposition for orthostatic
      intolerance following cardiovascular deconditioning would be markedly enhanced by
      blunted ability to reflexly activate the sympathetic nervous system.

PMID- 11458702
TI  - Dynamic modulation of baroreflex sensitivity in health and disease.
AB  - Assessment of arterial baroreflex function in humans through laboratory tests has
      provided a great deal of information of pathophysiological and clinical
      relevance. Indeed, the sensitivity of the baroreceptor-heart rate reflex
      quantified through these laboratory methods was shown to predict the risk of
      cardiovascular events and death from myocardial infarction, heart failure, and in
      diabetic patients. This traditional approach, however, does not provide
      information on daily life baroreflex cardiovascular control. Modern techniques,
      based on computer analysis of spontaneous blood pressure and heart rate
      fluctuations, are now available and allow baroreflex sensitivity to be assessed
      under real-life conditions with no need for external stimulation. In particular,
      these methods offer the possibility of investigating the dynamic modulation of
      baroreflex sensitivity occurring either on a minute-to-minute basis or over 24
      hours.

PMID- 11458703
TI  - The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes.
AB  - The Bezold-Jarisch reflex is an eponym for a triad of responses (apnea,
      bradycardia, and hypotension) following intravenous injection of veratrum
      alkaloids in experimental animals. The observation was first reported in 1867 by
      von Bezold and Hirt, and confirmed in 1938-1940 by Jarisch. The triad depends on
      intact vagi and is mediated through cranial nervous medullary centers controlling
      respiration, heart rate, and vasomotor tone. The respiratory effects are mediated
      through pulmonary vagal afferents and the bradycardia and vasodepression through
      cardiac vagal afferents. The veratrum alkaloids activate all known receptors in
      the carotid-aortic and cardiopulmonary areas. The cardiopulmonary receptors
      (baroreceptors, cough receptors, and parenchymal stretch receptors) also respond
      to other chemical substances: nicotine, capsaicin, venom, antihistaminics,
      halogenated anesthetics, diguanides, and serotonin (5-hydroxytryptamine).
      Derivatives of last-mentioned amine activate Type 1, 2, or 3 receptors and have
      potential therapeutic use. Since several types of cardiopulmonary receptors
      participate in the Bezold-Jarisch reflex, it has been difficult to develop a
      blockade to one type of receptor for therapeutic use (cough, bronchospasm,
      pulmonary hypertension, or coronary vasospasm). Axon reflexes influence pulmonary
      blood vessels, bronchial blood vessels, and bronchial smooth muscles. These
      intrapulmonary reflexes need further study as to how they relate to the Bezold
      Jarisch reflex in health and disease. The cardiopulmonary and carotid-aortic
      reflexes can serve as defense mechanisms against chemical hazards that are likely
      to be inhaled in the workplace and in the environment.

PMID- 11458704
TI  - Cardiorespiratory interactions in neural circulatory control in humans.
AB  - The reflex mechanisms and interactions described in this overview provide some
      explanation for the range of neural circulatory responses evident during changes
      in breathing. The effects described represent the integrated responses to
      activation of several reflex mechanisms, including peripheral and central
      chemoreflexes, arterial baroreflexes, pulmonary stretch receptors, and
      ventricular mechanoreceptors. These interactions occur on a dynamic basis and the
      transfer characteristics of any single interaction are, in all likelihood, also
      highly dynamic. Nevertheless, it is only by attempting to understand individual
      reflexes and their modulating influences that a more thorough understanding of
      the responses to complex phenomena such as hyperventilation, apnea, and
      obstructive sleep apnea can be better understood.

PMID- 11458705
TI  - Arterial baroreceptor and cardiopulmonary reflex control of sympathetic outflow
      in human heart failure.
AB  - Several observations indicate that the arterial baroreflex control of sympathetic
      nerve activity is preserved, even in advanced heart failure. These include: (1)
      augmentation of muscle sympathetic nerve activity burst amplitude and duration
      following a premature beat; (2) rapid recognition of changes in blood pressure
      induced by ventricular arrhythmias; (3) muscle sympathetic alternans and a steep
      inverse relationship between changes in diastolic pressure and the subsequent
      sympathetic burst amplitude during pulsus alternans; (4) similar inhibition of
      muscle sympathetic nerve activity in subjects with normal and impaired left
      ventricular systolic function by increases in intrathoracic aortic transmural
      pressure; (5) documentation, by cross-spectral analysis, of similar gain in the
      transfer function between blood pressure and muscle sympathetic nerve activity in
      these two groups; and (6) during sodium nitroprusside infusion, similar reflex
      increases in total body norepinephrine spillover in normal and heart-failure
      subjects. When nonhypotensive lower-body negative pressure was applied to test
      the hypothesis that selective reduction of atrial and pulmonary pressures would
      exert a cardiac sympathoinhibitory response in heart failure, there was no effect
      in control subjects, but cardiac norepinephrine spillover fell by 25% (P < .05)
      in those with systolic dysfunction. In summary, human heart failure is
      characterized by a rapidly responsive and sensitive arterial baroreflex, and by
      activation of a cardiac sympathoexcitatory reflex related to increased
      cardiopulmonary filling pressures.

PMID- 11458706
TI  - Cerebral autoregulation in orthostatic intolerance.
AB  - Many of the primary symptoms of orthostatic intolerance (fatigue, diminished
      concentration) as well as some of the premonitory symptoms of neurally mediated
      syncope (NMS) are thought to be due to cerebral hypoperfusion. Transcranial
      Doppler measurements of middle cerebral artery blood velocity (CBV) is at present
      the only technique for assessing rapid changes in cerebral blood flow, and hence
      for evaluating dynamic cerebral autoregulation. However, controversies exist
      regarding data interpretation. At syncope, during the collapse of blood pressure
      (BP), diastolic CBV diminishes, whereas systolic CBV is maintained. Some consider
      this increase in CBV pulsatility to be indicative of a paradoxical increase in
      cerebrovascular resistance (CVR) prior to syncope. Others note that mean CBV
      decreases much less than does mean BP, implying that cerebral autoregulatory
      mechanisms are intact and functioning at syncope. Similarly, there is no evidence
      of impaired dynamic cerebral autoregulation, as measured by standard linear
      transfer-function analysis, in patients with NMS. Some patients with exaggerated
      postural tachycardia (POTS) have been found to have an excessive decrease in CBV
      during head-up tilt. Controversy exists as to whether this decrease results from
      an excessive sympathetic outflow to the cerebral vasculature or from
      hyperventilation. However, many other equally symptomatic patients with a similar
      hemodynamic profile of exaggerated tachycardia during head-up tilt have normal
      CBV changes during this maneuver and have normal dynamic cerebral autoregulation
      as determined by transfer-function analysis. Whether these discrepancies reflect
      different pathologies in patients with POTS is currently unknown.

PMID- 11458707
TI  - Familial orthostatic tachycardia due to norepinephrine transporter deficiency.
AB  - Orthostatic intolerance (OI) or postural tachycardia syndrome (POTS) is a
      syndrome primarily affecting young females, and is characterized by
      lightheadedness, palpitations, fatigue, altered mentation, and syncope primarily
      occurring with upright posture and being relieved by lying down. There is
      typically tachycardia and raised plasma norepinephrine levels on upright posture,
      but little or no orthostatic hypotension. The pathophysiology of OI is believed
      to be very heterogeneous. Most studies of the syndrome have focused on
      abnormalities in norepinephrine release. Here the hypothesis that abnormal
      norepinephrine transporter (NET) function might contribute to the pathophysiology
      in some patients with OI was tested. In a proband with significant orthostatic
      symptoms and tachycardia, disproportionately elevated plasma norepinephrine with
      standing, impaired systemic, and local clearance of infused tritiated
      norepinephrine, impaired tyramine responsiveness, and a dissociation between
      stimulated plasma norepinephrine and DHPG elevation were found. Studies of NET
      gene structure in the proband revealed a coding mutation that converts a highly
      conserved transmembrane domain Ala residue to Pro. Analysis of the protein
      produced by the mutant cDNA in transfected cells demonstrated greater than 98%
      reduction in activity relative to normal. NE, DHPG/NE, and heart rate correlated
      with the mutant allele in this family. CONCLUSION: These results represent the
      first identification of a specific genetic defect in OI and the first disease
      linked to a coding alteration in a Na+/Cl(-)-dependent neurotransmitter
      transporter. Identification of this mechanism may facilitate our understanding of
      genetic causes of OI and lead to the development of more effective therapeutic
      modalities.

PMID- 11458708
TI  - Cardiac vagal chemosensory afferents. Function in pathophysiological states.
AB  - Stimulation of cardiac vagal afferent endings evokes reflex hypotension and
      bradycardia, also known as a Bezold-Jarisch effect. The physiological importance
      of this reflex pathway remains uncertain today, but it is increasingly apparent
      that cardiac vagal afferents can play an important role in modulating
      cardiovascular control in pathophysiological states, particularly myocardial
      ischemia. The afferent endings that compose this vagal input are functionally
      diverse. Ventricular endings exist that are stimulated by wall motion. However,
      cardiac chemosensitive endings, stimulated by a variety of metabolically active
      substances known to be produced by the stressed myocardium (e.g., bradykinin,
      prostaglandins, reactive oxygen species), play a major role in mediating reflex
      adjustments during myocardial ischemia. Data are presented highlighting the
      importance of arachidonic acid metabolites and oxygen radicals in activating
      cardiac vagal endings during myocardial ischemia and reperfusion, and their role
      in modulating cardiac afferent sensitivity in the disease states of heart failure
      and insulin-dependent diabetes.

PMID- 11458709
TI  - Cardiac sympathetic afferent activation provoked by myocardial ischemia and
      reperfusion. Mechanisms and reflexes.
AB  - Cardiac sympathetic afferents are known to reflexly activate the cardiovascular
      system, leading to increases in blood pressure, heart rate, and myocardial
      contractile function. During myocardial ischemia, these sensory nerves also
      transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The
      authors' laboratory has been interested in defining the mechanisms of activation
      of this neural system during ischemia and reperfusion. During these periods,
      reactive oxygen species, particularly hydroxyl radicals, are produced from the
      breakdown of purine metabolites and lead to stimulation of sympathetic (and
      vagal) ventricular chemosensitive nerve endings. For example, stimulation with
      hydrogen peroxide leads to a small reflex increase in blood pressure from the
      predominant sympathetic afferent activation that is reduced by simultaneous
      activation of cardiac vagal afferents (known to exert predominantly depressor
      reflexes). Central integration of these two opposing reflexes likely occurs at
      several regions of the brain stem, including the nucleus tractus solitarii, where
      neural occlusion occurs during simultaneous cardiac sympathetic and vagal
      afferent stimulation. Activation of platelets also appears to play a role during
      myocardial ischemia, leading to local release of serotonin (5HT), which, through
      a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in
      pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and
      may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down
      arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac
      sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents
      during ischemia and reperfusion and the resulting reflex events form a
      multifactorial process resulting from activation of a number of chemical pathways
      in the myocardium.

PMID- 11458710
TI  - Toward an understanding of the molecules that sense myocardial ischemia.
AB  - Cardiac afferent neurons are activated in the setting of myocardial ischemia and
      mediate the sensation of angina. However, the precise stimuli and receptive
      molecules responsible are not completely understood. To further investigate the
      molecular components involved, cardiac afferents were isolated in dissociated
      culture and patch-clamp experiments were performed on these cells. It was found
      that acidic pH evoked large inward currents in almost all cardiac sympathetic
      afferents. By comparison, the responses to other potential chemical mediators
      were inconsistent and much smaller. The biophysical properties of the acid-evoked
      currents in cardiac afferents match the acid-sensing ion channel 3 (ASIC3).

PMID- 11458711
TI  - Neuro-cardiovascular regulation: from molecules to man. Introduction.

PMID- 11458712
TI  - Lead us not into temptation: drug representatives.

PMID- 11458713
TI  - Suddenly disabled!

PMID- 11458714
TI  - A vision for the University of Missouri-Columbia School of Medicine.

PMID- 11458715
TI  - Defendant's medical malpractice claims: apportioning fault among the parties.

PMID- 11458716
TI  - Essentials of Medicare compliance.

PMID- 11458717
TI  - Combined transcervical transmastoid approach to giant parotid pleomorphic
      adenoma: a case report.
AB  - Although rare, giant major salivary gland pleomorphic adenomas are among the most
      astonishing patient presentations. Patients may ignore these slow-growing, benign
      lesions until significant functional impairment occurs. Complete tumor excision
      and facial nerve preservation in these cases are challenging requirements and are
      greatly aided by combined transcervical and transmastoid approaches to these
      lesions. In the presented case, facial nerve monitoring accurately identified the
      collateralization between the upper and lower divisions of the facial nerve and
      allowed the required sacrifice of the lower division without the need for facial
      nerve grafting or reconstruction. The patient recovered full function of all
      branches.

PMID- 11458718
TI  - [To "cuff" or "not to cuff"--that is the question].

PMID- 11458719
TI  - [The use of cuffed endotracheal tubes in infants and small children].
AB  - The use of endotracheal tubes with a cuff is controversial in infants and small
      children. Often anaesthetists advocate extreme opinions and whereas some
      propagate the use of cuffed tubes in all cases without restriction, others
      condemn their use in infants and small children under all circumstances. In this
      article, the discussion concerning the use of cuffed endotracheal tubes in
      infants and small children is based on current data and arguments. Relevant facts
      about the anatomy of the upper airway are reviewed and tube products that are
      currently available, their correct use in infants as well as the inherent
      potential advantages and disadvantages related to their use are discussed. The
      overall incidence of iatrogenic damage after short lasting endotracheal
      intubation is low. However, acquired subglottic stenosis might represent a severe
      long-lasting complication. Regardless as to whether tubes with or without cuffs
      are used, a disproportion between the outer diameter of the tube and the inner
      diameter of the nonexpandable cricoid ring is the main reason for the genesis of
      this lesion. A continuous monitoring of the cuff pressure is recommended when
      using cuffed endotracheal tubes in this age group.

PMID- 11458720
TI  - [Prevention of "post-sevoflurane delirium" with midazolam].
AB  - In a randomized double-blind placebo-controlled trial in children 2-7 years of
      age, we investigated the effect of a single prophylactic midazolam bolus (0.1
      mg/kg b.w.) prior to the termination of anaesthesia, on the incidence and
      severity of agitation occurring after sevoflurane administration. Compared to the
      placebo group, midazolam prophylaxis significantly decreased the incidence of
      postanaesthetic delirium. However, the incidence of severe agitation requiring
      treatment was not different between the groups (placebo: n = 6; midazolam: n =
      4). The mean severity of agitation was significantly lower in patients with
      midazolam prophylaxis. When midazolam was administered for the treatment of
      severe agitation it reduced the severity but did not abolish agitation. All
      patients were discharged from the recovery room after the 2 h observation period.
      From our study we conclude that a small prophylactic midazolam bolus is able to
      reduce the incidence and severity of agitation after sevoflurane anesthesia in
      some patients but is insufficiently effective in patients with severe agitation.
      Thus, the prophylactic administration of midazolam extenuates but does not solve
      the problem of post-sevoflurane agitation.

PMID- 11458721
TI  - [Urapidil for treatment of postanesthetic shivering following general anesthesia.
      A placebo controlled pilot study].
AB  - OBJECTIVE: Postanaesthetic shivering is common during recovery from general
      anaesthesia. Therefore we studied whether urapidil suppresses postanaesthetic
      shivering. METHODS: With written informed consent and approval of the local
      ethics committee, patients (ASA I-II) recovering from general anaesthesia were
      monitored for 1 h. Patients with continuous shivering for a period of 5 min were
      randomly treated either with 5 ml placebo (isotonic saline) or 25 mg urapidil in
      a double-blind trial. This treatment procedure was repeated if shivering did not
      stop. A complete suppression of shivering was appraised as a sufficient
      treatment. RESULTS: Shivering occurred in 20 of the patients studied and urapidil
      stopped shivering in 7 out of the 10 treated patients, whereas the placebo
      stopped shivering in only 2 out of 10 patients (P < 0.05). CONCLUSION: In a
      placebo controlled trial, it was demonstrated that postanaesthetic shivering can
      be successfully treated by urapidil in 70% of the patients.

PMID- 11458722
TI  - [Epidural abscess following delivery with peridural analgesia. The question of
      prevention].
AB  - A 35-year-old healthy gravida 2 para 2 developed a spinal epidural abscess after
      uneventful obstetric epidural analgesia. The diagnosis was confirmed by
      gadolinium-enhanced MRI; immediate surgical drainage combined with long-term
      antibiotic treatment led to complete recovery. The symptoms and possible
      contributing factors (e.g. immunological impairment of the patient, duration of
      the catheterization, violation of hygienic standards, type of disinfectant and
      dressing) are discussed. Vigilance is essential to avoid complications in
      patients with epidural catheters, even after it has been removed, in order to
      introduce appropriate diagnostic and therapeutic measures without delay.
      Immediate treatment is decisive for long term prognosis which should be
      introduced before neurological dysfunction appears.

PMID- 11458723
TI  - [Cytokines in neuropathic pain].
AB  - Cytokines are a heterogeneous group of polypeptides that were originally
      described to mediate activation of the immune system and inflammatory responses.
      Most of them have meanwhile been shown to be also produced by and act on the
      peripheral and central nervous system. There is ample evidence from experimental
      studies that proinflammatory cytokines induce or increase neuropathic pain as
      well as inflammatory pain. Direct actions of cytokines on afferent nerve fibers
      have been shown as well as actions involving further mediators such as
      prostaglandins or nerve growth factor. Inhibition of proinflammatory cytokines,
      either by synthesis inhibitors, inhibitors of cleavage from the cell membrane, by
      direct antagonists, or by anti-inflammatory antibodies, reduces pain and
      hyperalgesia in most models studied. Studies with cytokine knock-out animals
      often lead to different results from the pharmacological studies. This is in part
      due to compensatory mechanisms in the animals combined with the high redundancy
      of the cytokine system. Preliminary data from human studies are encouraging
      insofar as in the future, cytokine inhibition may add to the panel of treatment
      modalities for neuropathic pain.

PMID- 11458724
TI  - [Anesthesia for 100 years].

PMID- 11458725
TI  - [Blood volume--what brings us to the new millennium?].

PMID- 11458726
TI  - [Bicycling versus intensive care units--twice "hemoglobin doping"?].

PMID- 11458727
TI  - [Oxygen carriers--carriers in the future].

PMID- 11458728
TI  - [Werner Hugin--pioneer of anesthesiology in Switzerland].

PMID- 11458729
TI  - [Changeover of artificial respiration devices in anesthesia].

PMID- 11458730
TI  - [Parallel anesthesia].

PMID- 11458731
TI  - [Use of nitrous oxide and hospital planning].

PMID- 11458732
TI  - [Anesthesia for diagnostic procedures in a non-operating room area].

PMID- 11458733
TI  - The injured coach.
AB  - The patient in this case was diagnosed as having an epidural hematoma (shown in x
      ray at right). This results from hemorrhage between the dura mater and the skull.
      The hemorrhage may result from a traumatic insult to the side of the head, which
      can fracture the temporal bone and lacerate the middle meningeal artery. Since
      the hemorrhage is arterial in nature, the patient may deteriorate quickly. These
      patients may present with what is referred to as a "lucid interval." The patient
      typically has a significant blow to the head that results in a short period of
      unconsciousness. They then regain consciousness at a time that frequently
      coincides with the arrival of EMS. Once conscious, they are in a period known as
      the lucid interval. They will still have a headache, but may otherwise be acting
      normally and show no other physical findings on examination. Many such patients
      refuse treatment and transport. [table: see text] Inside the skull, however, the
      problem will grow. Broken arterial vessels are bleeding, causing an expanding
      hematoma. The patient typically will soon complain of a severe headache along
      with other associated complaints, such as nausea/vomiting, then will lose
      consciousness again and/or have a seizure. Initial physical findings may include
      contralateral weakness and a decreased Glasgow Coma score. As the hematoma
      expands, cerebral herniation may occur, compressing the third cranial nerve,
      which presents as a "blown pupil." EMS providers should have a high suspicion of
      injuries that affect the side of the head and the base of the skull. It is
      important to not only assess such injuries, but also the mechanism of injury, and
      to know the complications or later presentation that can arise from such
      injuries. Given that this patient was alert, oriented, not obviously intoxicated,
      and accompanied by his wife, the providers in this case would have had no choice
      but to abide by a refusal of treatment and transport. However, that could lead to
      serious complications, such as ongoing minor neurological deficits, later on. If
      this is the case, contacting medical control should be the priority.

PMID- 11458734
TI  - Closed for business: overcrowding in the ED.

PMID- 11458735
TI  - Assessment clues.

PMID- 11458736
TI  - Acute hyperventilation syndrome.

PMID- 11458737
TI  - 20 pearls of great EMS instruction.

PMID- 11458738
TI  - Anticonvulsant medications.
AB  - The understanding of epilepsy has advanced substantially in the past decade, and
      new anticonvulsant drugs with novel mechanisms of action are continually being
      developed. Some of these newer (and older) medications have been discussed in
      this article. A wide variety of other drugs is occasionally used in the
      management of epilepsy. Although parenteral magnesium sulfate is used mainly for
      the prevention and control of seizures in severe preeclampsia or eclampsia,
      parenteral magnesium sulfate may also be useful in controlling epileptic seizures
      associated with low plasma magnesium concentrations. Although considered
      obsolete, bromides have been useful in the management of tonic-clonic or
      myoclonic seizures in some infants and preadolescent children when other drugs
      were unsuitable. Acetazolamide may be useful in the management of refractory
      partial, myoclonic, absence or primary generalized tonic-clonic seizures;
      however, tolerance develops to the effect of the drug. Corticotropin and
      corticosteroids are sometimes used in the management of myoclonic seizures in
      infants. Steroids may be used in seizures due to intracerebral malignancies and
      metastasis but are more effective in blunting the intracranial swelling
      associated with these diseases. Recognition of these new drugs may allow the
      paramedic or EMT to identify seizure patients in the field. Knowledge of the side
      effects of these medications may be used to guide patients into appropriate
      treatment pathways.

PMID- 11458739
TI  - Responding to aquatic facilities.
AB  - The primary and fundamental responsibility of a local EMS system is to provide
      prehospital care to the citizens of the community. Therefore, each community must
      have a system in place to ensure continual, efficient prehospital care. There are
      a variety of levels of EMS education, which include first responder, EMT-Basic,
      EMT-Intermediate and EMT-Paramedic, along with other components, including the
      emergency medical dispatcher, other healthcare providers and specialty care
      centers. In order for a community to provide and ensure continual, efficient
      prehospital care, the components must work together in a well-planned and
      coordinated effort. If lifeguard personnel are expected to respond to
      respiratory, cardiac and spinal-injury incidents within their aquatic facilities,
      they must be included within this comprehensive community EMS system. Therefore,
      fire, rescue and other prehospital EMS agencies must coordinate their efforts and
      training responsibilities with the local lifeguard services in their area.

PMID- 11458740
TI  - AEDM 2001: solving the Asian equation.

PMID- 11458741
TI  - Spatial functional distribution in the corticospinal tract at the corona radiata:
      a three-dimensional anisotropy contrast study.
AB  - The spatial functional distribution of the nerve fibers was investigated in the
      corticospinal tract at the level of the corona radiata. Thirteen patients with
      corona radiata infarction underwent axial single-shot echo planar diffusion
      weighted magnetic resonance imaging using a 1.5 Tesla scanner. Image analysis
      used the three-dimensional anisotropy contrast (3DAC) method to demarcate the
      nerve fibers in the corticospinal tract. Axial 3DAC images demonstrated the
      corticospinal tract as a distinct area indicating nerve fiber integrity in all
      normal hemispheres and infarction as a dark or black area in affected
      hemispheres. Seven patients with upper extremity-dominant motor dysfunction had
      infarction located in the middle one third of the corticospinal tract. A patient
      with lower extremity-dominant motor dysfunction had infarction in the posterior
      one third. Five patients with equal motor dysfunction in the upper and lower
      extremities had infarction in both the middle and posterior one thirds of the
      corticospinal tract. The recovery of motor dysfunction at one month follow up
      correlated with the location of the corticospinal tract injury on the initial
      3DAC images. The findings of the 3DAC images provide an indicator of the pattern
      and the recovery from acute and chronic motor dysfunction in patients with corona
      radiata infarction.

PMID- 11458742
TI  - Involvement of fluctuating high blood pressure in the enlargement of spontaneous
      intracerebral hematoma.
AB  - The correlations between changes in blood pressure after admission and hematoma
      expansion were investigated in 118 patients with spontaneous intracerebral
      hematoma admitted within 24 hours of onset who underwent serial computed
      tomography. Multiple logistic regression was performed to assess correlations
      between hematoma enlargement and clinical characteristics on admission. Hematoma
      enlargement was predominantly correlated with time of onset (p = 0.01567), and
      not well correlated with blood pressure at admission (p = 0.07908). Serial
      changes in blood pressure were investigated in 57 patients admitted within 6
      hours of ictus whose blood pressures were monitored every hour from admission.
      Wilcoxon signed-rank analysis was used to determine the relationships between
      hematoma enlargement and blood pressure. Patients with hematoma enlargement was
      significantly correlated with increased blood pressure (p = 0.0004). Increases in
      blood pressure after admission may be a factor in hematoma enlargement.

PMID- 11458743
TI  - Delayed, transient neurological deterioration after mild head injury--case
      report.
AB  - A 16-year-old boy presented with delayed, transient neurological deterioration 18
      days after mild head injury. Left hemiparesis and left homonymous hemianopsia
      appeared after right frontal contusional and mild subdural hematomas subsided.
      Neuroimaging examinations including cerebral angiography, magnetic resonance
      imaging, and single photon emission computed tomography showed vasodilation and
      hyperemia in the right cerebral hemisphere. The present case is not typical of
      acute "juvenile head trauma syndrome," but may represent a possible
      pathophysiology of the delayed type of transient neurological deterioration after
      mild head injury.

PMID- 11458744
TI  - Spontaneous cerebrospinal fluid rhinorrhea associated with chronic renal failure-
      case report.
AB  - A 39-year-old woman was admitted with complaints of headache and nasal discharge
      on the left for 3 months which was later on proved to be cerebrospinal fluid
      (CSF). Neurological examination found no abnormalities except bilateral
      papilledema. Neuroimaging demonstrated enlargement of the lamina cribrosa
      foramina through which the olfactory nerves pass, as well as empty sella and
      cerebral cortical atrophy. Bone mineral densitometry showed osteopenia. CSF Ca++
      and blood parathyroid hormone levels were elevated. CSF pressure was 280 mmH2O.
      Bilateral frontal craniotomy was performed to expose the anterior fossa.
      Foraminal enlargement at the lamina cribrosa was confirmed, and islands of extra
      osseous calcifications on the arachnoid membrane were identified. The base of the
      anterior fossa was repaired intradurally with fascial graft and fibrin glue on
      both sides. No CSF leakage was noted at 1-year follow up. Spontaneous CSF leakage
      probably resulted from enlargement of the foramina at the lamina cribrosa due to
      Ca++ mobilization from bones and pseudotumor cerebri not to the extent of
      hydrocephalus caused by poor CSF absorption at the arachnoid granulations
      obliterated by extra-osseous calcareous accumulation.

PMID- 11458745
TI  - Spinal extradural arachnoid cyst--case report.
AB  - A 48-year-old male presented with progressive leg weakness. Magnetic resonance
      imaging and computed tomography myelography showed an extradural arachnoid cyst
      extending from the T-12 to L-2 levels in the thoracolumbar region. The cyst was
      confirmed at surgery and completely removed. This surgical intervention achieved
      improvement in the neurological symptoms.

PMID- 11458746
TI  - Cervical myelopathy due to compression by bilateral vertebral arteries--case
      report.
AB  - A 69-year-old man presented with progressive cervical myelopathy due to vascular
      compression of the upper cervical spinal cord. Vertebral angiography and magnetic
      resonance imaging revealed that the elongated bilateral vertebral arteries (VAs)
      had compressed the spinal cord at the C-2 level. The spinal cord was surgically
      decompressed laterally by retracting the VAs with Gore-Tex tape and anchoring
      them to the dura. The patient's symptoms improved postoperatively. Decompression
      and anchoring of the causative vessels is recommended due to the large size of
      the VAs.

PMID- 11458747
TI  - Two-staged operation for thoracolumbar osteomyelitis following methicillin
      resistant staphylococcus aureus infection of a craniectomy wound--case report.
AB  - A previously healthy 53-year-old woman developed pyogenic vertebral osteomyelitis
      (PVO) manifesting as progressive lumbago following wound infection of a
      decompressive craniectomy performed for brain contusion caused by a traffic
      accident. Magnetic resonance imaging disclosed vertebral osteomyelitis at T-12
      and L-1 with paravertebral abscess. Anterior debridement and fusion using
      autografts were performed at the first operation. Methicillin-resistant
      Staphylococcus aureus (MRSA) was cultured from the abscess specimen. Antibiotic
      therapy resolved the infection. Pedicle screw fixation was performed at the
      second operation. The patient became free from back pain and no recurrence of
      infection was seen. The diagnosis of PVO is frequently observed or delayed
      because of the nonspecific symptomatic presentation in the early stage.
      Coexistent infection or trauma makes early diagnosis more difficult. Indications
      and timing of instrumentation for the spinal column infected with MRSA is
      difficult. Two-staged operation with anterior debridement and posterior
      instrumentation after eradication of the infection is a safe and effective
      procedure for MRSA vertebral osteomyelitis.

PMID- 11458748
TI  - Surgeon's position for transsphenoidal surgery--technical note.
AB  - Transsphenoidal resection of pituitary tumors is usually performed with the
      surgeon standing on the patient's right side. However, this configuration is
      awkward when the tumor extends to the right and access may be hindered if the
      patient has poor nuchal flexibility or a large chest due to giantism or
      acromegaly. The surgeon stood on the left side of the patient during
      transsphenoidal surgery in five selected cases. The position on the left provided
      good access to the tumors with minimal changes in technique.

PMID- 11458749
TI  - [From veterinary companionship to veterinary consultation about dairy farms (by
      way of changing strategies in cattle practice)].
AB  - Dairy herd health and production management programmes are used by veterinary
      practices as a daily routine. However, the potential of this increasingly
      important source of income is probably not realized completely. The activities of
      dairy herd health and production management programmes were assessed by both
      veterinarians and dairy farmers. Subsequently, plans were developed to make herd
      health and production management programmes beneficial to both parties. For this
      purpose it is necessary to change the former dairy herd health and production
      management programme into a more professionally oriented veterinary consultancy.
      This article describes how this change can be made. Defining the consultancy
      programme and working in a structured way are essential to gain profit from
      veterinary consultancy.

PMID- 11458750
TI  - [Veterinary herd health consultancy on dairy farms: guidelines for starters].
AB  - This paper presents a guideline which can be used when setting up a professional
      veterinary herd health and production management advisory programme for dairy
      farms. Earlier research showed that dairy farmers prefer a structured
      professional programme and ask their veterinary surgeons to provide an optimal
      veterinary advisory programme for their dairy farms with a clear structure and
      contents, and well-planned activities. The guideline presented here should aid in
      providing the farmers with that clarity, structure, and planning. This should
      ultimately lead to a more professional implementation of veterinary advisory
      programmes.

PMID- 11458751
TI  - [Anesthesia practice 2000. How do we continue in 2001?].

PMID- 11458752
TI  - [Veterinary drugs, who cares?].

PMID- 11458753
TI  - [Who is the bitten dog? Legal liability for damage done by animals. Part 6].

PMID- 11458754
TI  - [Social network for veterinarians. Foot and mouth disease very emotional for
      some].

PMID- 11458755
TI  - [Careful consideration of the Spring Congress 2001].

PMID- 11458756
TI  - Factors related to utilization of traditional Chinese medicine in Taiwan.
AB  - Complementary and alternative medicine use is increasing worldwide. Expenses for
      complementary and alternative medicines are high, while the effectiveness of such
      medicines is still in debate. This paper reviewed the utilization of
      complementary and alternative medicines. Complementary and alternative therapies
      are used frequently and increasingly. Alternative therapies were used often for
      chronic conditions, including back problems, anxiety, depression and headaches in
      the United States. Musculoskeletal and respiratory complaints were the most
      frequent causes for complementary and alternative medicine consultation in
      Israel. In Taiwan, a systematic series of studies on factors related to
      utilization of traditional Chinese medicine (TCM) were conducted, including: (1)
      factors related to the choice of medical service (single or dual approach); (2)
      factors related to the choice of clinic type between TCM and western medicine
      among patients with single approach and among patients with dual approach; (3)
      factors related to patient choice of institute providing TCM (between TCM
      department in teaching hospital and regular TCM clinic) among patients using TCM
      only; and (4) knowledge, attitude and behavioral intention regarding TCM among
      patients using TCM only and among community residents over 30 years old. The
      findings of the above studies are summarized and presented accordingly.

PMID- 11458757
TI  - Automatic bone age estimation based on carpal-bone image--a preliminary report.
AB  - BACKGROUND: Bone age (BA) estimation is one of the important applications of hand
      radiography in the area of pediatrics, especially for the diagnosis of
      endocrinological problems and growth disorders. BA estimation (BAE) is tedious,
      time-consuming and highly dependent upon the expert experience. Nowadays, most
      BAE standards are based on American standards, but there is no BAE standard for
      Taiwanese people. We attempt to construct a computerized BAE system to automate
      BAE and in the long run to build a BAE standard for Taiwanese. METHODS: Our BAE
      system is based on the carpal bone information. We propose a new 2-stage edge
      detection method for carpal bone feature extraction and a new method for locating
      the carpal bone region of interest. RESULTS: After the image is manually
      equalized, our BAE system can estimate the bone age automatically. The extracted
      carpal bone features were applied to three classifiers for age estimation: the
      weighted minimum distance, Bayes, and neural network classifiers. The Bayes and
      neural network classifiers had better results. In the 0.5-year tolerance case,
      they both had over 90% correct rate for both male and female training data. In
      the 1-year tolerance case, they could classify correctly for the male and female
      testing data. CONCLUSIONS: A computerized BAE system has been developed and some
      experiments have been conducted. It is found that the classifying results for 0.5
      year tolerance are good and satisfactory.

PMID- 11458758
TI  - Endoscopic stenting in the treatment of bile leakage after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Bile leakage is one of the most common complications after
      laparoscopic cholecystectomy surgery, and biliary decompression is a key factor
      in treatment. We retrospectively investigated 6 patients with bile leakage after
      laparoscopic cholecystectomy who were treated with endoscopic stent. METHODS:
      From March 1995 to May 1999, six patients (4 men and 2 women) aged 30-64 years
      (mean, 51 years) with bile leakage after laparoscopic cholecystectomy were
      enrolled. Biliary stent (10 French, 6-10 cm) placement with (n = 4) or without (n
      = 2) sphincterotomy was attempted. The symptoms, results and outcomes were
      reviewed. RESULTS: The interval from operation to presentation of bile leakage
      ranged from 1 to 10 days. Bile leakage was detected from cystic duct stump in 5
      patients (83%) and from right IHD in 1 patient (17%). Plastic stent placement was
      successfully in all patients. Endoscopic stenting healed bile leakage
      successfully in 5 cases (83%). One patient required surgical correction due to
      persistent bile leakage. The mean duration between stent placement and cessation
      of bile leakage was 6.8 days (range 1 to 24 days). CONCLUSIONS: Endoscopic
      stenting is a safe, rapid and effective treatment for bile leakage after
      laparoscopic cholecystectomy.

PMID- 11458759
TI  - The role of lymphadenectomy in the radical nephrectomy for renal cell carcinoma.
AB  - BACKGROUND: The value of lymphadenectomy in the management of renal cell
      carcinoma (RCC) remains controversial. Most would agree that lymphadenectomy (LD)
      provides accurate pathologic staging for prognostic data. The question remains
      whether there is any significant therapeutic benefit from extensive lymph node
      dissection with radical nephrectomy. The aim of this study was to compare
      outcomes in sampled lymphadenectomy (SLD) and extensive lymphadenectomy (ELD)
      with radical nephrectomy for RCC. METHODS: One hundred and thirty-seven patients
      with RCC were enrolled in this study from Oct. 1982 to Dec. 1996. Eighty-one
      patients received radical nephrectomy with SLD (stage I: 43, II: 16, III: 22).
      Fifty-six patients received radical nephrectomy with ELD (stage I: 30, II: 11,
      III: 15). RESULTS: The mean number of lymph nodes removed by SLD was 4 (ranged
      from 1 to 8). The mean number of lymph nodes removed by ELD was 16.1 (ranged from
      9 to 32). Overall 5-year survivals for SLD in stages I, II and III were 98%, 80%
      and 38%, respectively. Overall 5-year survivals for ELD in stages I, II and III
      were 92%, 84% and 40%, respectively. CONCLUSIONS: There is no significant
      therapeutic benefit from ELD in patients with RCC receiving radical nephrectomy.

PMID- 11458760
TI  - Risk factors of catheter-related infections in total parenteral nutrition
      catheterization.
AB  - BACKGROUND: The use of central venous catheter for administration of total
      parenteral nutrition (TPN) is a risk factor of catheter-related infections (CRIs)
      that are associated with increased morbidity and mortality, prolonged
      hospitalization, and increased medical costs. The purpose of this study is to
      evaluate the risk factors of CRIs in patients with administration of TPN.
      METHODS: A total of 1134 patients receiving TPN between January, 1996 and
      December, 1998 were studied. The category of infection included definite catheter
      related bloodstream infection (CR-BSI), probable CR-BSI, and insertion site
      infection. Statistical analysis of risk factors was performed. RESULTS: A total
      of 131 episodes of CRI occurred, representing an infection rate of 11.46%. Ninety
      three episodes (8.1%) had probable CR-BSI, 13 episodes (1.1%) had definite CR
      BSI, and 25 episodes (2.2%) had insertion site infection. Duration of TPN
      infusion and frequency of catheter insertion showed statistically significant
      difference by logistic regression multivariate analysis. The isolated organisms
      were in sequence of coagulase-negative Staphylococci (19.4%), Staphylococcus
      aureus (17.2%) and Candida albicans (14.4%). CONCLUSIONS: Risk factors
      influencing the occurrence of CRI in TPN administration were multifactorial;
      however, duration of TPN infusion and frequency of catheter insertion were the
      main factors in our study.

PMID- 11458761
TI  - Treatment of intractable generalized dystonia by bilateral posteroventral
      pallidotomy--one-year results.
AB  - BACKGROUND: Recent study has revealed that bilateral posteroventral pallidotomy
      (PVP) significantly improve dystonic movements and improve motor function of
      those patients with generalized dystonia (GD). However, there is only a limited
      number of patients who have been reported so far. METHODS: This study was
      conducted to evaluate the clinical efficacy of surgical treatment with bilateral
      PVP on patients with intractable GD. All the studied patients were regularly
      rated with standardized scales (Burke-Fahn-Marsden Evaluation Scale for Dystonia)
      for dystonic movement and living disability before and after surgery. RESULTS:
      There were 18 patients, 8 males and 10 females with an average age of 24.8 years,
      included in the study. Postoperatively, there were slow, partial, but steady
      improvements of the dystonic movement and daily living function. Maximal effects
      were noted at the sixth month and the clinical benefits were sustained one year
      after the surgical treatment when there were statistically significant
      improvements in 13% of total dystonia movement score and 9% of the total
      disability score (p < 0.05). Upon further analysis, improvements of dystonic
      movements were statistically significant in the regions of mouth (50%),
      speech/swallowing (19%) and neck (43%), and daily living functions in speech
      (14%) and eating/swallowing (29%). CONCLUSIONS: Bilateral posteroventral
      pallidotomy was only partially effective for the treatment of GD, and it produced
      clinical improvement in the dystonic movement limited to the craniocervical
      region. We therefore suggest that patients with GD should be carefully selected
      for the treatment of bilateral posteroventral pallidotomy, despite the surgery
      having a partially beneficial effect on this kind of movement.

PMID- 11458762
TI  - Fournier's gangrene--Taiwan experience.
AB  - BACKGROUND: Synergistic necrotizing fascitis of the scrotum, penis and perianal
      region was first described by Fournier in 1883. If not recognized early, this
      infectious process will extend along the fascia plane to the lower abdominal and
      back regions, causing severe morbidity and even mortality. METHODS: The records
      of 8 patients diagnosed of Fournier's gangrene were reviewed between 1988 and
      2000. The sex, age, etiology, associated diseases, bacteriological studies and
      treatments were analyzed. RESULTS: The 8 patients were all males, age ranging
      from 42 to 78 years old, with average 55.1 years. Six patients were due to
      perianal abscess, one patient was a complication of hemorroidectomy, and one
      patient had traumatic injury of scrotum. Six patients had poor controlled
      diabetes mellitus, and there were two patients with cirrhosis of the liver and
      hepatoma, respectively. Even with aggressive treatments, two patients died; the
      other 6 recovered completely. The mortality rate was 25%. CONCLUSIONS: Fournier's
      gangrene is a not common but life-threatening disease which needs radical
      debridement and effective antibiotics to control the infection and early
      reconstruction with skin graft and myocutaneous flaps. Mortality is usually due
      to delayed diagnosis.

PMID- 11458763
TI  - Adenomyosis and uterus rupture during labor.
AB  - A spontaneous uterus rupture occurred during the labour of a 37-week-pregnant
      woman showing a precocious rupture of membranes. It appeared enlarged and the cut
      surface of the myometrium showed coarse trabeculations. The histological
      examination showed a hypertrophic gravidic myometrium with heterogeneous areas of
      fibrosis and adenomyosis, necrotic decidual foci and hyperplastic cervical canal
      glands. Our experience suggests that a silent and spontaneous uterine rupture, is
      possible even in the absence of the principal risk factors.

PMID- 11458764
TI  - Anterior pituitary failure (panhypopituitarism) with balanced chromosome
      translocation 46,XY,t(11;22)(q24;q13).
AB  - Hypopituitarism is the clinical syndrome that results from failure of the
      anterior pituitary gland to produce its hormones. Hypopituitarism can result
      from: (1) intrinsic or primary pituitary disease; (2) intrinsic hypothalamic or
      secondary pituitary disease; or (3) extrinsic extrasellar or parasellar disease.
      The etiologies of primary hypopituitarism are miscellaneous. The dominant
      clinical picture of hypopituitarism in the adult is that of hypogonadism. Reports
      have associated hypopituitarism with anti-pituitary-antibodies, hereditary
      syndrome and chromosome defects, but hypopituitarism has rarely been associated
      with balanced chromosome translocation (11;22)(q24;q13). Here, we describe a case
      of anterior pituitary failure with balanced chromosome translocation. A 19-year
      old Chinese teenager presented with failure of pubertal development and sexual
      infantilism. On examination, the patient had the classic appearance of
      hypogonadism. Endocrine studies and three combined pituitary function tests
      revealed panhypopituitarism. A chromosomal study revealed
      46,XY,t(11;22)(q24;q13), a balanced translocation between 11q24 and 22q13. Chest
      films showed delayed fusion of bilateral humeral head epiphyses and bilateral
      acromions. Scrotal sonography revealed testes were small bilaterally. Magnetic
      resonance imaging (MRI) of the sella revealed pituitary dwarfism. The patient
      received 19 months replacement therapy, including steroids (prednisolone 5 mg
      each day), L-thyroxine (Eltroxin 100 ug each day), and testosterone enanthate 250
      mg every two weeks. His height increased 4 cm with secondary sexual
      characteristics developed, and muscle power increased.

PMID- 11458765
TI  - An unusual cutaneous metastasis from hepatocellular carcinoma.
AB  - Cutaneous metastases from hepatocellular carcinoma are rare. In this report we
      detail a case of hepatocellular carcinoma with the unusual manifestations of
      multiple skin metastases. A 49-year-old male, who had received surgical resection
      of hepatocellular carcinoma one year prior, presented with multiple reddish-blue,
      firm, painless and nonulcerative cutaneous papules and nodules over the fingers,
      palms, toes, soles and back. Pathology of the cutaneous nodules showed
      characteristic hepatocellular carcinoma with trabecular gland formation. These
      lesions grew very rapidly and developed to cauliflower appearances which had not
      been described previously in the literature. The patient died of respiratory
      failure secondary to lung metastasis two months after the first appearance of the
      skin lesions.

PMID- 11458766
TI  - Validation of ethylene oxide-sterilization using a new measuring system.
AB  - Up to now the parametric release of medical devices sterilized with EO was not
      possible due the lack of an online method of measurement for EO. With the
      developed mobile system it is possible to measure all physical parameters of the
      sterilization process online in the chamber. The accuracy of the EO concentration
      and humidity measurement is < +/- 1%, of the temperature < +/- 0.05 degree C and
      of pressure < 0.5% of the measured value.

PMID- 11458767
TI  - [Laser Doppler imaging and cryoglobulinemia].
AB  - Continuous microcirculation monitoring of the right foot was carried out for the
      first time in a 62-year-old patient with cryoglobulinaemia prior to, during and
      after manual needle insertion at Jie Xi(St.41) acupuncture point using a new
      method of laser Doppler perfusion imaging (PIMII, Lisca AB, Linkoping, Sweden).
      In addition to visual inspection, changes in mean perfusion were also used as
      evaluation parameters. Our results suggest that the new biomedical technique of
      laser Doppler imaging is a useful method for monitoring the effects of
      acupuncture on the peripheral microcirculation.

PMID- 11458768
TI  - [Miniaturization capable, very sensitive polarimeter as detector of an
      implantable glucose probe. I. Optical amplification of the measuring value].
AB  - From a clinical point of view, an implantable telemetric probe for monitoring the
      blood glucose profile is highly desirable. It should be capable of monitoring the
      blood glucose level continuously or at regular brief intervals, if necessary
      requirement-controlled. Apart from blood, measurement can also be made in
      intercellular tissue fluid, for example, in subcutaneous connective and fatty
      tissue, because this fluid accurately reflects blood glucose levels after only a
      brief, but negligible, time lag. Since the functional lifespan of an implantable
      probe is of decisive importance, only physical sensors, but not bio-sensors can
      be considered. We are in the process of developing a very sensitive miniaturised
      detector based on polarimetry, capable of determining the measuring parameter-
      the spatial orientation of the in-plane vibration of a polarised light beam--with
      extreme accuracy. This is a very important point, since the physiological and
      pathological glucose levels modify the in-plane vibration by only a very tiny
      angle of rotation. The high level of accuracy is achieved by various specific
      optical amplification mechanisms, and amplification of the electric signal. Two
      purely optical amplification methods are described here. Simple linear elongation
      of the optical path of a laser beam within the sample, resulting in a
      proportional amplification of the measuring signal, is obviously strictly limited
      in an implantable probe. We therefore developed a technique that preserves the
      polarisation state of the light beam during reflection. This technique makes
      possible multiple passage of the light beam through the fluid being sensed, thus
      elongating the optical path by "folding" the light beam without the need to
      enlarge the measuring cuvette. In a second possibility, enlargement of the
      rotation angle can be achieved by reflecting the light beam from a suitable
      surface, when the orthogonal components of the polarised light beam are reflected
      to different extents.

PMID- 11458769
TI  - Averaging of strongly varying signals.
AB  - Forces acting at the hip joint during a given activity often vary much between
      trials and subjects. Large variations are also encountered in many other
      biomechanical signals. Arithmetic mean curves then lead to falsified results,
      especially if extreme values occur at very different times. A method was
      developed for calculating a typical curve from such varying, time dependent
      signals. All cycle times are first averaged and the signals are then more and
      more smoothed using Fourier series with decreasing numbers of harmonics. The
      remaining extrema are analysed to decide whether they are typical for all curves
      or not. This is done by systematically cutting off a varying number of extrema at
      the beginning or end of all curves. After this an equal number of extrema remains
      in all curves. These extrema are then shifted to average positions in time, i.e.
      the times between consecutive extrema are compressed or expanded, and the
      standard deviation of all curves is calculated. The combination of cut off
      extrema which results in the smallest standard deviation is then used further on.
      The same time distortions are applied to the original curves and their arithmetic
      mean finally results in the typical signal. This procedure is well suited for
      averaging hip contact forces and other varying signals as long as their
      complexity and variation is not extremely large.

PMID- 11458770
TI  - [Evaluation of hydroxyapatite-coated Schanz screws in the Heidelberg external
      fixation system (HEFS)].
AB  - The use of monolateral external fixation systems for the correction of limb
      length and/or axial anomalies involves the implantation of Schanz screws in the
      long bones for periods of weeks or months. The loosening rate, which increases
      with duration of implantation, is a problem. In animal experiments/superior
      fixation and a reduced infection rate have been reported for hydroxyapatite
      coated screws in comparison with conventional screws. We report on the clinical
      application of 59 hydroxyapatite-coated Schanz screws in 15 external fixation
      mountings. The performance of the screws was evaluated by clinical and
      radiological criteria. Infection was seen in 15 screws, necessitating the early
      removal of 6 of them. In patients with a second fixation system/the infection
      rate was lower, with infection developing in only 1 of 12 screws.

PMID- 11458771
TI  - Design and construction of a simulator for testing finger joint replacements.
AB  - A simulator for testing finger joint replacements was developed. Movement
      intervals of 15 degrees at flexion and extension plain can be set using an
      adjustable crank drive. The maximum range of motion is 105 degrees, 90 degrees
      being the maximum flexion and 15 degrees the extension. Thus, the simulator is
      also suitable for impingement tests. A constant joint load is infinitely variable
      from 20 N to 500 N. Test frequency is also infinitely variable from 0.2 Hz to 2
      Hz. A modular assembly of the components of the prosthesis means that these can
      be positioned as required, and that any type of prosthesis may be tested. The
      design and the material allow for an all-round lubrication at a heat up to 37
      degrees C. The equipment is designed for permanent operation. Pre-clinical
      quality assurance for finger joint replacements can be considerably improved by
      the implementation of the present simulator.

PMID- 11458772
TI  - [What is your diagnosis? Bannwarth syndrome (acute Lyme neuroborreliosis)].

PMID- 11458773
TI  - [Does refractive surgery really make eyeglasses superfluous?].
AB  - Spectacles have become a problem of life-style in some societies. In the USA, in
      1999 approximately 1 million LASIK operations have been performed to correct
      myopia and astigmatism and in Europe the frequency of refractive surgery stead by
      increases. However, only 3 to 5% of these operations are medically indicated.
      Refractive surgery is evaluated regarding safety and efficacy. Modern laser
      techniques demonstrate excellent refractive results: photorefractive keratectomy
      (PRK) achieved refractive success rates of 90% and more with complication rates
      of 0.5% and less. PRK is, therefore, a valuable technique for corrections of
      myopia up to -6.0 D. Similar efficacy is obtained with LASIK (laser in situ
      keratomileusis) in corrections up to -10 D, however, the complication rate is
      somewhat higher. Laser correction of hyperopia is equally successful regarding
      the refractive success but shows an even higher complication rate and the patient
      satisfaction is lower. Modern refractive laser surgery may replace spectacles in
      the majority of the cases, however, none of the techniques is free of
      complications. Therefore, we understand refractive surgery still to be inferior
      to the correction of ametropia by means of spectacles and any such operation
      should be attempted only after thorough discussion.

PMID- 11458774
TI  - [Ventricular tachycardia].
AB  - In patients with ventricular tachycardias, various structural and functional
      conditions can be influenced by certain triggers, initiating the mechanism of the
      arrhythmia. Thorough understanding of these different factors is paramount for
      the appropriate choice of treatment. Several options are available for the
      management of ventricular tachycardias: antiarrhythmic drugs, ICD implantation
      and catheter ablation or a combination of the above. The prognosis of an
      individual patient is determined by the underlying disease, the mechanism of
      tachycardia and the selected therapy. The complexity of several conditions
      requires a specialized diagnostic approach and tailored medical management.
      Therefore the patients with the following diagnoses should be referred to a
      specialized electrophysiology center: survivors of sudden cardiac death old
      infarct scar, reduced ejection fraction and complex ectopy Cardiomyopathy with
      syncope or ventricular tachycardias Long QT-Syndrome Brugada Syndrome Right
      Ventricular Dysplasia recurrent syncopes of unclear etiology.

PMID- 11458775
TI  - [Thoracic pain from the viewpoint of the gastroenterologist: diagnosis and
      therapy].
AB  - Non-cardiac-chest-pain is frequently associated with esophageal diseases.
      Gastroesophageal reflux disease (GERD) is present in 60%, esophageal motility
      disorder in 40-50%, tumours in 5-10% and achalasia in 5% of such cases. Diagnosis
      is based on endoscopy and in patients with no endoscopy findings on 24-h
      esophageal pH-monitoring. GERD can present with various symptoms and can best be
      managed with proton pump inhibitors (PPI). Considering increased mortality and
      morbidity operation should only be performed in special situations. Esophageal
      motility disorders most frequently produce retrosternal pain. Pain in achalasia
      may not respond to standard therapy. Motility disorders and achalasia are
      diagnosed by perfusion manometry and videofluoroscopy. If a tumour is suspected
      diagnosis is made by endoscopy (biopsy, endosonography) and radiology.

PMID- 11458776
TI  - [Growth disorders in the child].
AB  - The ability to interpret growth of a child is dependent on the availability of
      earlier data of the child and of data concerning the family. Most important is
      the recording of growth data on a growth chart by the family doctor or the
      paediatrician. In addition, parental height allows the calculation of the
      patients target height. The exact interpretation of bone age using a x-ray of the
      hand is imperative. The most common "disturbances of growth" are variants of the
      norm, like familial short stature or retardation of growth and development, or-
      not rarely--a combination of both. A simple flow sheet is helpful in determining
      if further endocrine investigation are needed.

PMID- 11458777
TI  - [Burning tongue in a 47-year-old housewife].

PMID- 11458778
TI  - ["I don't believe what I'm seeing": Charles Bonnet syndrome].

PMID- 11458779
TI  - [Percutaneous gastrostomy with balloon PEG balloon replacement tubes by the
      radiologist. An interventional technique for simple placement of feeding
      catheters without surgical or endoscopic intervention].
AB  - Patients afflicted with stenotic head and neck or esophageal tumors often require
      artificial enteral feeding. Frequently passage of an endoscope through the
      esophagus is impossible in these patients. Interventional, fluoroscopically
      assisted, percutaneous gastrostomy (PG) by balloon replacement tubes is a
      feasible and successful alternative to percutaneous endoscopic gastrostomy (PEG)
      and the method of choice in patients where the esophagus cannot be passed with an
      endoscope anymore. Technical success rate is very high and serious complications
      are rare. Radiological PG is a feasible, equivalent alternative to PEG also in
      all other patients. We recommend PG with balloon gastrostomy tubes in conjunction
      with gastropexy performed with three to four T-fasteners, which are left in place
      for seven days in order to prevent dislocation and leakage.

PMID- 11458780
TI  - [New knowledge regarding tumor cell inactivation and histological evaluation
      after radiofrequency therapy. Single case observation and in vitro proof of a new
      hypothesis].
AB  - In a study, a radiofrequency (RF) treatment was performed on a patient with a
      small breast cancer after vacuum biopsy. As usual in cases with a malignant
      diagnosis, surgical excision and axillary dissection followed. Histopathology
      revealed some residual tumor in the margin of the cavity. It could not be
      distinguished from vital tumor on the hematotoxylin eosin (HE) stain. Based on
      the correlation of MRI and histopathology after subsequent surgical excision, we
      did, however, presume that the residual was contained within the zone of
      inactivation. Thus the hypothesis arose that, if too high temperatures can be
      avoided, it might be possible to inactivate tumor cells without significantly
      impairing histopathologic assessment. This hypothesis was supported by the
      following in vitro experiment performed on a fresh specimen: An RF treatment was
      performed using temperatures up to 70 degrees C only. Half of the specimen
      underwent HE-staining, the other half vitality testing. The results indicate that
      if a given temperature range is strictly observed it appears possible to
      inactivate tissue before tissue sampling, since histopathologic diagnosis will
      not be impaired. Further technologic improvements may eventually allow to develop
      a pre-treatment method which might permit to avoid potential hematogenous tumor
      spread during subsequent biopsy.

PMID- 11458781
TI  - [Cutting speeds and success of biopsy with different punch biopsy instruments].
AB  - PURPOSE: The goal of our investigations was the verification of the relationship
      between the reachable cutting speed and the biopsy success for different large
      core needle biopsy devices in dependence of the cutting depth as well as
      different kinds of tissue. METHODS: We measured the dynamic cutting properties of
      five large-core needle devices with moveable outer needles in air and different
      tissues. An incremental stripe had been attached on to the outer needle and was
      moved through a photooptical sensor during the cutting phase. For the valuation
      of the biopsy success we compared the absolute weight respectively the volume of
      the tissue probes as well as the relative weight in relation to the size of the
      sample chambers within the inner trocars. RESULTS: A clear correlation between
      the cutting speed, the tissue properties and the biopsy success had been
      registered, especially for more solid tissues. CONCLUSIONS: For a successful
      large-core needle biopsy a cutting speed of 8 to 12 metres per second is
      essential. To compensate slower needle movements high quality requirements for
      the surface, geometry and edge have to be fulfilled.

PMID- 11458782
TI  - [Computerized tomography evaluation of local recurrence of operated and adjuvant
      radiation treated rectal carcinoma. Normal and pathological changes after
      operation and irradiation of rectal carcinoma in 956 CT examinations].
AB  - Colorectal carcinoma is one of the most common cancer in Germany. We want to
      evaluate the most reliable CT features indicating local recurrence of rectal
      cancer as early as possible. 232 patients suffering from rectal cancer being
      administered to our clinic from 1987-1998 were investigated. Criteria for
      inclusion: patients after surgery and radiotherapy of rectal cancer with a
      minimum follow-up of two years and at least 3 CT examinations. All CT
      examinations were analyzed standardized. The main target parameters for relapse
      were enlargement of a presacral mass, inhomogeneous appearance, asymmetric
      outlines, enlarged lymph nodes and infiltration of the surrounding structures. An
      unchanged appearance of the presacral space in more than three CT examinations
      after surgery correlated with freedom of recurrence.

PMID- 11458783
TI  - [Quantitative computerized tomography of bone mineral density of the mandible.
      Imaging of topographic distribution of bone mineral density in automated
      segmentation of mandibular structures].
AB  - PURPOSE: Confirmation of a new technique for evaluating bone mineral density
      (BMD). Colored coded imaging of topographical distribution of bone mineral
      density in the spongy substance. METHOD: For 20 patients, dental CT examinations
      of the mandible were made in axial slices. Spongy substance and cortical bone
      pixels were automatically segmented at foramina mentalia level by means of
      threshold fixation. The segments were separated in areas relevant to
      implantology. For each region, BMD was measured by means of quantitative computed
      tomography (QCT). Spongiose substance of 20 mandibles was segmented by using
      three threshold intervals to image topographical BMD distribution. RESULTS:
      Cortical bone and spongy substance could be automatically segmented for 20
      mandibles. BMD could be measured in each region. The results were comparable with
      those of other techniques. Three threshold intervals were segmented for 20
      mandibles in the spongy substance to depict topographical BMD distribution.
      CONCLUSIONS: Areas of low BMD can be detected by imaging topographical BMD
      distribution. This way, subjective rating by the examiner is eliminated.

PMID- 11458784
TI  - [Histiocytosis X of the lung after successfully treated pulmonary metastatic
      ovarian carcinoma].
AB  - We report a case of a woman who developed a pulmonary histiocytosis X after
      treatment of an ovarian cancer with intrapulmonary metastases. Development of
      histiocytosis X seems to be coincidental and not to be therapy induced. Inspired
      by this case radiological findings of pulmonary histiocytosis X are presented.

PMID- 11458785
TI  - [Imaging of coronary vascular abnormality with aneurysm and arteriovenous fistula
      using MRI bolus tracking].
AB  - Coronary arteriovenous fistulas are very rare findings and predominantly drain
      into the right atrium or the right ventricle. Echocardiography and x-ray coronary
      angiography are established methods in the detection of this anomalies. It is
      reported on a patient, in whom an anomaly with dilatation of the circumflex
      coronary artery, aneurysma and drainage over an arteriovenous fistula in the
      right ventricle was observed. By means of magnetic resonance tomography with
      bolustracking technique the vessel course and the dynamics of perfusion are
      noninvasive shown beside the imaging using TSE-sequence. The method of multiple
      injections of 2 ml Gd-DTPA makes the bolustracking technique to an ideal tool for
      the determination of the individual vessel course, the haemodynamics and draining
      direction of an coronary anomaly with fistula.

PMID- 11458786
TI  - [Reference manager EndNote 4. Further development and new functions].
AB  - Bibliography database managers are used to manage information resources:
      specifically, to maintain a database of references and create bibliographies and
      reference lists for written works. It should offer tools that let you find and
      retrieve references quickly, and it should be able to produce the bibliography in
      the format required for a particular publication. There are many computer
      programs, but very few stands out as truly useful, time saving, and work
      enhancing. One of them is EndNote. The reference manager EndNote 4 was recently
      released in Germany and, as long-time fans of this excellent program, we upgraded
      from the previous version. The use of the software package EndNote 4 for Windows
      is described, and we want to report about our own experiences with the new
      version of this database manager. The main reason for getting EndNote 4 is its
      clearly improved functions and features: for instance a new library window, a
      better search functions, an automatic updates and completion of term lists and an
      improved identification of duplicate references. Altogether EndNote 4 provides
      also an excellent combination of features and ease of use.

PMID- 11458787
TI  - [Osteolysis of the fibula. Desmoplastic fibroma of the fibula].

PMID- 11458788
TI  - [Sectional diagnosis of orbital tumors. 2: Extra-conal compartment, subperiostal
      compartment, lacrimal gland, bulbus, preseptal compartment].

PMID- 11458789
TI  - [Diagnosis and therapy of chronic cough].

PMID- 11458790
TI  - [Diagnostic criteria and therapeutic attitudes in fungemia].

PMID- 11458791
TI  - [Management of chronic cough in high volume medical offices: efficacy of a
      sequential protocol].
AB  - INTRODUCTION: Chronic cough is one of the main causes of medical consultation.
      There is not however an homogeneous attitude regarding its management. A
      prospective evaluation was performed of a simple therapeutic protocol based on
      the anatomical approach of the cough reflex. METHODS: A total of 110 patients
      with chronic cough for longer than four weeks were studied. The exclusion
      criteria were: non-smoking during the last year, not to have diseases
      compromising the immune system and not to have received inhibitors of the
      angiotensing converting enzyme. A three-visit stepwise approach was performed
      with specific diagnostic tests ordered and a specific therapy instituted
      according to the clinical suspicion. RESULTS: At the third visit, 97% of patients
      were free from cough or had improved markedly. Cough causes were identified in
      105 cases (95%) and the most common were: asthma (33%), postnasal dripping (29%),
      gastroesophageal reflux (10%), and asthma with associated gastroesophageal reflux
      (16%). Patients with asthma had a longer duration of tos compared with those who
      had postnasal dripping (p < 0.05) as the only differential feature. CONCLUSIONS:
      The diagnostic-therapeutic diagram based on the anatomic reflex of cough is
      useful for the management of chronic cough in a highly demanded medical office.
      With this protocol, the cause of cough can be identified and treated successfully
      in almost every patient with a small number of diagnostic tests and medical
      visits.

PMID- 11458792
TI  - [Usefulness of the clonidine test for the diagnosis of pheochromocytoma].
AB  - BACKGROUND: The clonidine test has been proposed as diagnostic biochemical test
      for patients with clinical suspicion of pheochromocytoma. METHODS: The clonidine
      test was used in 80 patients with suspicion of pheochromocytoma (on account of
      suggestive clinical findings, increased levels of metanephrines, increased plasma
      or urinary levels of catecholamines, or suggestive images by ultrasonography or
      CT). RESULTS: Surgery confirmed the diagnosis of pheochromocytoma in 16 patients.
      The highest sensitivity (62%) and specificity (46%) of the clonidine test
      corresponded to a brake degree of 5%, with a predictive negative value of 83%.
      The test was most useful in patients with increased basal plasma values of
      catecholamines (sensitivity, 62%; specificity, 66%). CONCLUSIONS: The clonidine
      test can be useful for the diagnosis of pheochromocytoma in patients with
      increased basal plasma levels of catecholamines and a brake degree lower than 5%
      at 180 minutes.

PMID- 11458793
TI  - [Study of cases of HIV infection in Castile-Leon prisons].
AB  - OBJECTIVE: To study the HIV infection cases among inmates in Castile-Leon prisons
      and the therapy status and clinical follow-up. MATERIALS Y METHODS: The socio
      demographic, clinical and virological parameters were studied of all seropositive
      inmates of seven out of eight prisons in Castile-Leon. A personal survey and a
      review of the medical records were conducted. RESULTS: A total of 413 HIV
      infected inmates were detected (12.05% out of 3,426 inmates); 98.6% were males,
      mostly of them caucasians. Parenteral drug abuse accounted for most infections
      (94.9%). Co-infection with hepatitis C virus was present in 81.4%, whereas the
      presence of surface antigen of the hepatitis B virus was detected in 12.6%. The
      median of CD4 lymphocyte count was 426.5 (interquartile range: 264.25 to 598.50)
      and of viral load 3.69 logs of particles/ml (interquartile range: 2.18 to 4.45).
      A total of 171 individuals are on anti-retroviral therapy, most of them with
      triple therapy; 40.4% of them had a viral load below 400 copies/ml. Over one
      third of seropositive individuals (37.3%) required therapy and are not on
      therapy, either because they have not initiated therapy or because of non
      compliance. CONCLUSIONS: A highly representative study of the area which reveals
      a low number of identified seropositive individuals, mainly in association with
      drug abuse. The therapeutic guidelines are the standards but there is a high
      percentage of individuals requiring therapy. Co-infection with hepatitis C virus
      is extremely high, which will undoubtedly pose new therapeutic approaches.

PMID- 11458794
TI  - [Sensitivity, specificity and predictive value of the genetic analysis of SLC3A1
      gene variants used for the diagnosis of cystinuria among the spanish population].
AB  - OBJECTIVE: To test the clinical usefulness of the analysis of point mutations
      R452W, M467T, 114C > A, 231T > A, 1136 + 3delT and 1332 + 7T > C in the gene
      SLC3A1 as well as their possible haplotypes used for the diagnosis of cystinuria
      in the mediterranean spanish population. MATERIAL AND METHODS: A total of 48
      patients with cystinuria, 44 relatives without cystinuria, and 81 healthy
      controls were studied. A genetic analysis was conducted in order to identify
      variants in the gene SLC3A1. The sensitivity, specificity, and predictive value
      for each genetic variant and for the possible haplotypes were calculated.
      RESULTS: The specificity of mutations M467T, R452W, and 231T > A used for the
      diagnosis of cystinuria in the general population or for the different subtypes
      of cystinuria in involved families, was higher than 90%; nevertheless, none of
      the analysed variants reached a sensitivity higher than 80%. In the study of
      haplotypes, the highest sensitivity was obtained with the haplotype CTTT (83.8%);
      however, its specificity and predictive value were low (20.6% and 53.4%,
      respectively). CONCLUSIONS: The studied genetic variants did not show enough
      clinical usefulness.

PMID- 11458795
TI  - [Functional foods in Europe].

PMID- 11458796
TI  - [Radiology of the biliary tract].

PMID- 11458797
TI  - [Cold-induced urticaria. Diagnostic and therapeutic management].

PMID- 11458798
TI  - [Treatment of vertigo].

PMID- 11458799
TI  - [Practical advise fo the prevention of infectious diseases to travellers of risk
      areas].

PMID- 11458800
TI  - [Woman with arthritis of the right knee].

PMID- 11458801
TI  - [Ramsay-Hunt syndrome].

PMID- 11458802
TI  - [Lower limb ischaemia in a patient with HCV hepatitis treated with alpha
      interferon. Brouer classification type III cryoglobulinemia].

PMID- 11458803
TI  - [Headache and diagnostic imaging. Aspergillosis sinusitis].

PMID- 11458804
TI  - [53 Year-old woman with fever, anemia and convulsions. Systemic lupus
      erythematosis central nervous system].

PMID- 11458805
TI  - [Acute cholestatic hepatitis as the presenting form of primary extranodal non
      Hodgkins lymphoma].

PMID- 11458806
TI  - [Inflammatory pseudotumor: presentation of two cases].

PMID- 11458807
TI  - [Hypercalcemia secondary to primary ectopic hyperparathyroidism].

PMID- 11458808
TI  - [Blistering cutaneous lesions in a patient with systemic lupus erythematosis].

PMID- 11458809
TI  - [Multiple myeloma and small cell lung carcinoma].

PMID- 11458810
TI  - [Abdominal aortic aneurysm and myocardial infarction: apropos of a case].

PMID- 11458811
TI  - [Pericarditis from Mycobacterium avium-intracellulare].

PMID- 11458812
TI  - Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) for
      advanced-stage Hodgkin's disease: CALGB 8856.
AB  - Successful treatment of advanced-stage Hodgkin's disease (HD) may critically
      depend on dose intensity. Because mechlorethamine, Oncovin, procarbazine, and
      prednisone (MOPP), and Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)
      are not suitable for major dose escalation, we evaluated the activity and
      toxicity of combined cyclophosphamide, doxorubicin, vincristine, prednisone, and
      etoposide (CHOPE) in advanced HD, here used at conventional dose intensity, as a
      preparatory study prior to using this regimen at higher dose intensity. Ninety
      two patients were treated with CHOPE (cyclophosphamide, 750 mg/m2, day 1;
      doxorubicin, 50 mg/m2, day 1; vincristine, 1.4 mg/m2, days 1 and 8; prednisone,
      100 mg/day, days 1-5; and etoposide, 80 mg/m2, days 1, 2, and 3) every 21 days.
      All had advanced HD with no prior chemotherapy with 46% stage IV, 63% with B
      symptoms, and 57% with bulky disease (> 5 cm). Radiation and growth factor
      support were not permitted. Full-dose vincristine (not capped at maximum 2
      mg/dose) was used in the first 33 patients. An initial cohort of 41 patients was
      treated with four cycles of CHOPE to evaluate safety and efficacy followed by
      four cycles of ABVD. A second cohort of 51 patients was treated with 6-8 cycles
      of CHOPE alone. Toxicity was generally acceptable and primarily hematologic, with
      neutrophils < 500 in 63% of cohort I and 90% of cohort II, and platelets < 25,000
      in 7% of cohort I and 8% of cohort II. The long-term neurotoxicity of full-dose,
      high-intensity vincristine was acceptable and largely reversible. In cohort I,
      92% of patients achieved a complete response (CR) or partial response (PR) with
      four cycles of CHOPE and 85% were in CR after four additional cycles of ABVD. In
      cohort II, 77% achieved a CR with 6-8 cycles of CHOPE alone. FFS was 76% in
      cohort I and 59% in cohort II, with a median follow-up of 8.2 and 5.7 years,
      respectively. CHOPE, at conventional dose intensity as used here, is an effective
      first-line regimen for the treatment of advanced-stage HD and may warrant
      evaluation using higher doses of cyclophosphamide and etoposide with granulocyte
      colony stimulating factor (G-CSF) support.

PMID- 11458813
TI  - Phase I-II vinorelbine (Navelbine) by continuous infusion in patients with
      metastatic breast cancer: cumulative toxicities limit dose escalation.
AB  - Vinorelbine (Navelbine) has significant activity against breast carcinoma and is
      less neurotoxic than vinblastine. Because vinblastine has improved activity when
      administered by continuous infusion, we conducted a Phase I-II study to determine
      the maximum tolerated dose (MTD) of vinorelbine when given by continuous infusion
      and the response rates to it in heavily pretreated metastatic breast cancer
      patients. Between April 1994 and August 1997, 87 patients were entered in the
      study. All were female and had proven metastatic breast cancer. Ninety-five
      percent of them had received prior doxorubicin treatment, and 74% had received
      prior paclitaxel treatment. In Phase I of the study, all patients received 8 mg
      of vinorelbine by intravenous (i.v.) bolus followed by a continuous infusion of
      vinorelbine over 96 hr. When the MTD was determined, patients were entered in the
      Phase II arm to assess treatment responses and cumulative toxic reactions. In the
      Phase I arm (43 patients, 182 cycles), we determined the MTD of vinorelbine to be
      8 mg by i.v. bolus followed by a continuous infusion of 11 mg/m2/day over 4 days.
      The dose-limiting toxic reaction was grade 3-4 granulocytopenia in 35% of the
      cycles and neutropenic fever in 15% of the cycles. Forty-four patients (193
      cycles) were treated at the MTD. Seven (16%) of them had a response (2 complete
      responses, 5 partial responses). The median durations of response and survival
      were 4.3 and 8.6 months, respectively. However, cumulative toxic reactions
      (neutropenic fever and stomatitis) in 22 patients (50%) required dose reductions.
      A continuous infusion of vinorelbine can be safely administered but with a narrow
      therapeutic index because of cumulative toxic reactions. We recommend a modified
      MTD of vinorelbine: 8 mg by i.v. bolus followed by a continuous infusion of 10
      mg/m2/day over 4 days. However, this treatment schedule offers no apparent
      advantage over the commonly used weekly vinorelbine schedule.

PMID- 11458814
TI  - A phase I-II trial of topotecan and gemcitabine in patients with previously
      treated, advanced non-small cell lung cancer (LOA-3).
AB  - The purposes of this study were to determine the maximum tolerated dose (MTD),
      dose-limiting toxicity (DLT), toxicity profile, and antitumor activity of
      topotecan (TOP) and gemcitabine (GEM) combination therapy when administered to
      patients with previously treated, advanced, non-small cell lung cancer. Both
      compounds were administered intravenously over 30 min, with TOP on days 1-5 and
      GEM on days 1 and 5 only. Nineteen patients were treated with 75 courses at three
      dose levels. The MTD was 0.75 and 400 mg/m2 for TOP and GEM, respectively, with
      thrombocytopenia and neutropenia as the DLTs. Partial responses were achieved in
      3 of 17 patients (18%) with measurable disease. Six patients (32%) had disease
      stabilization for at least four courses of treatment. The median survival was 10
      months from the initiation of TOP and GEM. This combination was relatively well
      tolerated and exhibited promising antitumor activity in patients with advanced,
      previously treated, non-small cell lung cancer.

PMID- 11458815
TI  - Cell density-dependent proliferative effects of transforming growth factor (TGF)
      beta 1, beta 2, and beta 3 in human chondrosarcoma cells HCS-2/8 are associated
      with changes in the expression of TGF-beta receptor type I.
AB  - In this study, the growth properties of the human chondrosarcoma cell line HCS
      2/8, its response to transforming growth factor (TGF)-beta isoforms 1, 2, and 3,
      and its expression of TGF-beta receptors I and II were examined. We demonstrated
      that these tumor cells are not contact-inhibited and that they can proliferate in
      the absence of additional serum growth factors. In sparse cultures, all TGF-beta
      forms inhibited the growth of HCS-2/8 cells, whereas they induced a 2-fold
      increase of DNA synthesis in serum-fed confluent cultures. In serum-free
      confluent conditions only TGF-beta 1 stimulated the proliferation rate, whereas
      TGF-beta 2 was without effect and TGF-beta 3 was rather inhibitory. This bimodal
      effect of TGF-beta forms was associated with a greater level of TGF-beta receptor
      1 mRNA in confluent HCS-2/8 than in sparse cultures, suggesting that the growth
      response to TGF-beta forms is dependent on the receptor profile expressed.

PMID- 11458816
TI  - Human leukocyte antigens (HLA)-Cw as prognostic indicators in autologous
      transplantation for lymphoma.
AB  - The human leukocyte antigens (HLA) function as transplantation antigens and as
      markers in disease association. Disparity at the HLA A, B, Cw, and DR loci in
      allogeneic stem cell transplants results in an increased incidence of graft
      versus-host disease, graft rejection, and decreased survival. HLA class I loci A,
      B, and Cw also function as ligands for natural killer (NK) cell receptors in an
      interaction that predominantly inhibits cytolysis of target antigens. This HLA-NK
      cell inhibitory function is required for protection against auto-aggression, and
      is of unclear significance in other clinical settings. Furthermore, the
      prevention of auto-aggression is HLA molecule specific as demonstrated by the
      association of specific HLA types with autoimmune diseases. It is not known
      whether the HLA molecules might serve as markers for outcome in autologous
      transplants. We investigated an association of HLA class I molecules and early
      transplant outcome in a cohort of patients who underwent autologous
      transplantation for the treatment of lymphoma. In this retrospective study, HLA
      class I molecules were analyzed to determine whether they affect transplant
      outcome. HLA typing was performed by microlymphocytotoxicity assays. Factors such
      as age, sex, disease type, lactate dehydrogenase (LDH), cell dose, type of graft,
      and transfusion events were reviewed. Outcome was defined as death (or survival)
      at 6 months from the date of transplant. HLA-Cw8 was significantly associated
      with poor outcome (odds ratio = 18 and 9.3, p = 0.01 and 0.02 in homozygous and
      all patients, respectively). The HLA-A and B locus molecules were not associated
      with outcome. Age, sex, elevated LDH, and cell dose were not associated with
      outcome. A blood progenitor cell dose of greater than 6 x 10(8) nucleated
      cells/kg was favorably associated with outcome (p = 0.08). The number of
      transfusions received was not associated with outcome. In the multivariate
      analysis of HLAs and factors associated with outcome, HLA-Cw8 emerged as an
      independent risk factor for poor outcome (p = 0.03) following autologous
      transplantation in lymphoma patients. The association of HLA-Cw molecules with
      outcome in this study group indicates a need for further investigation of the HLA
      mediated interactions that affect antitumor cytotoxicity, cytokine release, and
      regimen related toxicity.

PMID- 11458817
TI  - Current status of ribozymes as gene therapy agents for cancer.

PMID- 11458818
TI  - Magnetic resonance imaging and spectroscopic imaging of prostate cancer.

PMID- 11458819
TI  - Understanding the interaction between environmental exposures and molecular
      events in colorectal carcinogenesis.

PMID- 11458820
TI  - Selenium in cancer prevention: clinical issues and implications.

PMID- 11458821
TI  - The HER-2/neu oncogene in tumors of the gastrointestinal tract.
AB  - The HER-2/neu oncogene is localized to chromosome 17q and shares significant
      homology with the epidermal growth factor receptor. As a result of its potential
      role in the selection of therapy, HER-2/neu testing has reached near-standard-of
      practice status in breast cancer. There is considerable interest in HER-2/neu as
      a prognostic factor and target of therapy in tumors of the gastrointestinal
      tract. In this review of HER-2/neu expression in esophageal squamous cell
      carcinoma and adenocarcinomas of the esophagus, stomach, and colon, a wide range
      of expression of HER-2/neu from 0 to 83% likely reflects both differences in
      methods and reagents, as well as study bias associated with patient selection
      (i.e., early versus advanced disease). For esophageal squamous cell carcinoma,
      little information exists as to the prognostic significance of HER-2/neu
      expression. In adenocarcinoma associated with Barrett's esophagus there is
      contradictory data. However, most of the information available indicates that
      this marker has significant prognostic value. In gastric adenocarcinoma, the wide
      expression range may truly reflect patient selection because HER-2/neu positivity
      appears linked to advanced rather than early disease with limited invasion. The
      majority of studies favor a significant prognostic value of HER-2/neu status for
      this tumor. Finally, in colorectal cancer HER-2/neu overexpression also appears
      to be a significant adverse outcome indicator as judged by the current published
      literature. In conclusion, given that either HER-2/neu protein overexpression or
      gene amplification is associated with approximately one-fourth of all
      gastrointestinal tract malignancies, strategies designed to employ the marker in
      therapy selection appear warranted. During the next several years it will not be
      surprising to see these tumors treated with antiHER-2/neu modalities such as
      Herceptin, likely in combination with other agents initially for patients with
      advanced disease, and possibly for individuals with high-risk lesions in an
      adjuvant setting.

PMID- 11458822
TI  - Musical predispositions in infancy.
AB  - Some scholars consider music to exemplify the classic criteria for a complex
      human adaptation, including universality, orderlying development, and special
      purpose cortical processes. The present account focuses on processing
      predispositions for music. The early appearance of receptive musical skills, well
      before they have obvious utility, is consistent with their proposed status as
      predispositions. Infants' processing of musical or music-like patterns is much
      like that of adults. In the early months of life, infants engage in relational
      processing of pitch and temporal patterns. They recognize a melody when its pitch
      level is shifted upward or downward, provided the relations between tones are
      preserved. They also recognize a tone sequence when the tempo is altered so long
      as the relative durations remain unchanged. Melodic contour seems to be the most
      salient feature of melodies for infant listeners. However, infants can detect
      interval changes when the component tones are related by small-integer frequency
      ratios. They also show enhanced processing for scales with unequal steps and for
      metric rhythms. Mothers sing regularly to infants, doing so in a distinctive
      manner marked by high pitch, slow tempo, and emotional expressiveness. The pitch
      and tempo of mothers' songs are unusually stable over extended periods. Infant
      listeners prefer the maternal singing style to the usual style of singing, and
      they are more attentive to maternal singing than to maternal speech. Maternal
      singing also has a moderating effect on infant arousal. The implications of these
      findings for the origins of music are discussed.

PMID- 11458823
TI  - Intracerebral evoked potentials in pitch perception reveal a functional asymmetry
      of the human auditory cortex.
AB  - One acoustic feature that plays an important role in pitch perception is
      frequency. Studies on the processing of frequency in the human and animal brain
      have shown that the auditory cortex is tonotopically organized: low frequencies
      are represented laterally whereas high frequencies are represented medially. To
      date, the study of the functional organization of the human auditory cortex in
      the processing of frequency has been limited to the use of either scalp-recorded
      auditory evoked potentials (AEPs), which have relatively poor spatial resolving
      power, or functional imagery techniques, which have poor temporal resolving
      power. The present study uses intracerebrally recorded AEPs to explore this topic
      in the primary and secondary auditory cortices of both hemispheres of the human
      brain. Recordings were carried out in 45 adult patients with drug-resistant
      partial seizures. In the right hemisphere, clear spectrally organized tonotopic
      maps were observed with distinct separations between different frequency
      processing regions. AEPs for high frequencies were recorded medially, whereas
      AEPs for low frequencies were recorded laterally. In the left hemisphere,
      however, this tonotopic organization was less evident, with different regions
      involved in the processing of a range of frequencies. The hemisphere-related
      difference in the processing of tonal frequency is discussed in relation to pitch
      perception.

PMID- 11458824
TI  - The neural processing of complex sounds.
AB  - This paper considers the temporal processing of complex sounds relevant to
      musical analysis. Functional imaging studies, using positron emission tomography
      (PET), functional magnetic resonance imaging (fMRI), and magnetoencephalography
      (MEG), and the psychophysical assessment of patients with lesions allow two
      different approaches to this. Functional imaging allows the determination of
      structures normally involved in temporal analysis, while patient studies allow
      inference about the necessary structures for temporal analysis. Both approaches
      suggest a hierarchal organization in the brain corresponding to the processing of
      music. The features of individual notes are analyzed in the pathway up to and
      including the auditory cortices, while higher-order patterns formed by those
      features are analyzed by distributed networks in the temporal lobe and frontal
      lobes distinct from the auditory cortices.

PMID- 11458825
TI  - Music and the neurologist. A historical perspective.
AB  - Neurological disorders affecting musical function can produce either positive or
      negative symptoms. Positive phenomena include musicogenic epilepsy (seizures
      triggered by music), musical partial seizures (hallucinated music as the
      expression of the seizure), musical release hallucinations (nonepileptic musical
      hallucinations, usually associated with impaired hearing), and synesthesia
      (hallucinated colors triggered by musical tones). Negative phenomena comprise the
      amusias, which can be receptive, expressive, or both, and can selectively involve
      particular components of musical processing, including pitch, interval, contour,
      rhythm, meter, timbre, and emotional response. Amusia is often accompanied by
      aphasia, but each can occur in the absence of the other. Neurological disorders
      provide evidence that musical processing is multimodal and widely distributed in
      both cerebral hemispheres.

PMID- 11458826
TI  - Brain specialization for music. New evidence from congenital amusia.
AB  - Brain specialization for music refers to the possibility that the human brain is
      equipped with neural networks that are dedicated to the processing of music.
      Finding support for the existence of such music-specific networks suggests that
      music may have biological roots. Conversely, the discovery that music may have
      systematic associations with other cognitive domains or variable brain
      organization across individuals supports the view that music is a cultural
      artifact. Currently, the evidence favors the biological perspective. There are
      numerous behavioral indications that music-specific networks are isolable in the
      brain. These neuropsychological observations are briefly reviewed here with
      special emphasis on a new condition, that of congenital amusia (also commonly
      referred to as tone deafness).

PMID- 11458827
TI  - Cerebral substrates for musical temporal processes.
AB  - Music as well as language consists of a succession of auditory events in time,
      which require elaborate temporal processing. Although several lines of evidence
      suggest that the left dominant hemisphere is predominantly involved in the
      processing of rapid temporal changes of speech, very little is known about the
      cerebral substrates underlying such auditory temporal processes in music. To
      investigate this issue, we examined epileptic patients with either left (LTL) or
      right (RTL) temporal lobe lesions as well as normal control subjects (NC) in two
      different tasks involving the processing of time-related (temporal) information.
      By manipulating the interonset interval (IOI) in a psychophysical task, as well
      as in a task of detection of rhythmic changes in real tunes, we studied the
      processing of temporal microvariations in music. The first task assessed
      anisochrony (or irregularity) discrimination of sequential information according
      to different presentation rates (between 80 and 1000 ms IOI). For all subjects,
      an effect of tempo was obtained; thresholds were lower for the 80 ms IOI than for
      longer IOIs. Furthermore, there was a specific impairment of rapid anisochronous
      discrimination (80 ms IOI) for LTL patients as compared to RTL and NC subjects,
      but no deficit was observed for longer IOIs. These findings suggest the
      specialization of left temporal lobe structures in processing rapid sequential
      auditory information. The second task involved the detection of IOI increments in
      familiar monodic tunes. Performance was measured for two increments (easy vs.
      difficult to detect according to cognitive expectation) to assess the effect of
      cognitive expectation using a forced-choice paradigm (changed vs. unchanged
      melody). The results showed that LTL patients but not RTL were impaired as
      compared to NC subjects in the increment detection. However, all groups showed
      differences between the two levels of difficulty, suggesting that top-down
      processing remains functional. These findings suggest that left temporal lobe
      structures are predominantly involved in perceiving time-related perturbations in
      familiar tunes as well as in isochronous sequences, extending to the musical
      domain findings previously reported in speech.

PMID- 11458828
TI  - The quest for universals in temporal processing in music.
AB  - Music perception and performance rely heavily on temporal processing: for
      instance, each event must be situated in time in relation to surrounding events,
      and events must be grouped together in order to overcome memory constraints. The
      temporal structure of music varies considerably from one culture to another, and
      so it has often been supposed that the specific implementation of perceptual and
      cognitive temporal processes will differ as a function of an individual's
      cultural exposure and experience. In this paper we examine the alternative
      position that some temporal processes may be universal, in the sense that they
      function in a similar manner irrespective of an individual's cultural exposure
      and experience. We first review rhythm perception and production studies carried
      out with adult musicians, adult nonmusicians, children, and infants in order to
      identify temporal processes that appear to function in a similar fashion
      irrespective of age, acculturation, and musical training. This review leads to
      the identification of five temporal processes that we submit as candidates for
      the status of "temporal universals." For each process, we select the simplest and
      most representative experimental paradigm that has been used to date. This leads
      to a research proposal for future intercultural studies that could test the
      universal nature of these processes.

PMID- 11458829
TI  - Cerebral substrates of musical imagery.
AB  - Musical imagery refers to the experience of "replaying" music by imagining it
      inside the head. Whereas visual imagery has been extensively studied, few people
      have investigated imagery in the auditory domain. This article reviews a program
      of research that has tried to characterize auditory imagery for music using both
      behavioral and cognitive neuroscientific tools. I begin by describing some of my
      behavioral studies of the mental analogues of musical tempo, pitch, and temporal
      extent. I then describe four studies using three techniques that examine the
      correspondence of brain involvement in actually perceiving vs. imagining familiar
      music. These involve one lesion study with epilepsy surgery patients, two
      positron emission tomography (PET) studies, and one study using transcranial
      magnetic stimulation (TMS). The studies converge on the importance of the right
      temporal neocortex and other right-hemisphere structures in the processing of
      both perceived and imagined nonverbal music. Perceiving and imagining songs that
      have words also involve structures in the left hemisphere. The supplementary
      motor area (SMA) is activated during musical imagery; it may mediate rehearsal
      that involves motor programs, such as imagined humming. Future studies are
      suggested that would involve imagery of sounds that cannot be produced by the
      vocal tract to clarify the role of the SMA in auditory imagery.

PMID- 11458830
TI  - Neural specializations for tonal processing.
AB  - The processing of pitch, a central aspect of music perception, is neurally
      dissociable from other perceptual functions. Studies using behavioral-lesion
      techniques as well as brain imaging methods demonstrate that tonal processing
      recruits mechanisms in areas of the right auditory cortex. Specifically, the
      right primary auditory area appears to be crucial for fine-grained representation
      of pitch information. Processing of pitch patterns, such as occurs in melodies,
      requires higher-order cortical areas, and interactions with the frontal cortex.
      The latter are likely related to tonal working memory functions that are
      necessary for the on-line maintenance and encoding of tonal patterns. One
      hypothesis that may explain why right-hemisphere auditory cortices seem to be so
      important to tonal processing is that left auditory regions are better suited for
      rapidly changing broad-band stimuli, such as speech, whereas the right auditory
      cortex may be specialized for slower narrow-band stimuli, such as tonal patterns.
      Evidence favoring this hypothesis was obtained in a functional imaging study in
      which spectral and temporal parameters were varied independently. The hypothesis
      also receives support from structural studies of the auditory cortex, which
      indicate that spectral and temporal processing may depend on interhemispheric
      differences in grey/white matter distribution and other anatomical features.

PMID- 11458831
TI  - Exploring the functional neuroanatomy of music performance, perception, and
      comprehension.
AB  - This chapter highlights findings by my colleagues and me in four neuroimaging and
      neurological studies of music performance, perception, and comprehension. These
      investigations elucidate the neural subsystems supporting musical pitch, melody,
      harmony, rhythm, tempo, meter, and duration. In a positron emission tomography
      (PET) study of pianists, a memorized performance of a musical piece was
      contrasted with that of scales to localize brain areas specifically supporting
      music. A second PET study assayed brain areas subserving selectively the
      comprehension of harmony, melody, and rhythm. Musicians sight-read a score while
      detecting specific melodic, harmonic, or rhythmic errors in its heard
      performance. In a third PET study, musicians and nonmusicians discriminated pairs
      of rhythms with respect to pattern, tempo, meter, or duration. Data in these
      studies implicated the cerebellum in nonmotor, nonsomatic, sensory, or cognitive
      processing. In a fourth study, neurological patients with degeneration of the
      cerebellum were found to be impaired in fine discrimination of pitch. Overall,
      these data suggest that the neural systems underlying music are distributed
      throughout the left and right cerebral and cerebellar hemispheres, with different
      aspects of music processed by distinct neural circuits. Also discussed are key
      issues for interpreting the role in music of brain areas implicated in
      neuroimaging studies.

PMID- 11458832
TI  - Comparison between language and music.
AB  - Similarities and differences between language and music processing are examined
      from an evolutionary and a cognitive perspective. Language and music cannot be
      considered single entities; they need to be decomposed into different component
      operations or levels of processing. The central question concerns one of the most
      important claims of the generative grammar theory, that is, the specificity of
      language processing: do the computations performed to process language rely on
      specific linguistic processes or do they rely on general cognitive principles?
      Evidence from brain imaging results is reviewed, noting that this field is
      currently in need of metanalysis of the available results to precisely evaluate
      this claim. A series of experiments, mainly using the event-related brain
      potentials method, were conducted to compare different levels of processing in
      language and music. Overall, results favor language specificity when certain
      aspects of semantic processing in language are compared with certain aspects of
      melodic and harmonic processing in music. By contrast, results support the view
      that general cognitive principles are involved when aspects of syntactic
      processing in language are compared with aspects of harmonic processing in music.
      Moreover, analysis of the temporal structure led to similar effects in language
      and music. These tentative conclusions must be supported by other brain imaging
      results to shed further light on the spatiotemporal dynamics of the brain
      structure-function relationship.

PMID- 11458833
TI  - Musical sound processing in the human brain. Evidence from electric and magnetic
      recordings.
AB  - Recently, our knowledge regarding the brain's ability to represent invariant
      features of musical information even during the performance of a simultaneous
      task (unrelated to the sounds) has accumulated rapidly. Recordings of the change
      specific mismatch negativity component of event-related brain potentials have
      shown that temporally and spectrally complex sounds as well as their relations
      are automatically processed by human auditory cortex. Furthermore, recent
      magnetoencephalographic and positron emission topographic investigations indicate
      that this processing differs between phonetic and musical sounds within and
      between the cerebral hemispheres. These data thus suggest that despite the focus
      of listeners' conscious attention, relatively complex sound phenomena can be
      encoded by neural mechanisms that are specialized for musical sounds.

PMID- 11458834
TI  - How many music centers are in the brain?
AB  - When reviewing the literature on brain substrates of music processing, a puzzling
      variety of findings can be stated. The traditional view of a left-right dichotomy
      of brain organization--assuming that in contrast to language, music is primarily
      processed in the right hemisphere--was challenged 20 years ago, when the
      influence of music education on brain lateralization was demonstrated. Modern
      concepts emphasize the modular organization of music cognition. According to this
      viewpoint, different aspects of music are processed in different, although partly
      overlapping neuronal networks of both hemispheres. However, even when isolating a
      single "module," such as, for example, the perception of contours, the
      interindividual variance of brain substrates is enormous. To clarify the factors
      contributing to this variability, we conducted a longitudinal experiment
      comparing the effects of procedural versus explicit music teaching on brain
      networks. We demonstrated that cortical activation during music processing
      reflects the auditory "learning biography," the personal experiences accumulated
      over time. Listening to music, learning to play an instrument, formal
      instruction, and professional training result in multiple, in many instances
      multisensory, representations of music, which seem to be partly interchangeable
      and rapidly adaptive. In summary, as soon as we consider "real music" apart from
      laboratory experiments, we have to expect individually formed and quickly
      adaptive brain substrates, including widely distributed neuronal networks in both
      hemispheres.

PMID- 11458835
TI  - Music, cognition, culture, and evolution.
AB  - We seem able to define the biological foundations for our musicality within a
      clear and unitary framework, yet music itself does not appear so clearly
      definable. Music is different things and does different things in different
      cultures; the bundles of elements and functions that are music for any given
      culture may overlap minimally with those of another culture, even for those
      cultures where "music" constitutes a discrete and identifiable category of human
      activity in its own right. The dynamics of culture, of music as cultural praxis,
      are neither necessarily reducible, nor easily relatable, to the dynamics of our
      biologies. Yet music appears to be a universal human competence. Recent
      evolutionary theory, however, affords a means for exploring things biological and
      cultural within a framework in which they are at least commensurable. The
      adoption of this perspective shifts the focus of the search for the foundations
      of music away from the mature and particular expression of music within a
      specific culture or situation and on to the human capacity for musicality. This
      paper will survey recent research that examines that capacity and its
      evolutionary origins in the light of a definition of music that embraces music's
      multifariousness. It will be suggested that music, like speech, is a product of
      both our biologies and our social interactions; that music is a necessary and
      integral dimension of human development; and that music may have played a central
      role in the evolution of the modern human mind.

PMID- 11458836
TI  - The brain of musicians. A model for functional and structural adaptation.
AB  - Musicians form an ideal subject pool in which one can investigate possible
      cerebral adaptations to unique requirements of skilled performance as well as
      cerebral correlates of unique musical abilities such as absolute pitch and
      others. There are several reasons for this. First, the commencement of musical
      training usually occurs when the brain and its components may still be able to
      adapt. Second, musicians undergo long-term motor training and continued practice
      of complicated bimanual motor activity. Third, imaging studies from our group as
      well as other groups have shown that motor learning and the acquisition of skills
      can lead to changes in the representation of motor maps and possibly also to
      microstructural changes. Whether the unique musical abilities and structural
      differences that musicians' brains show are due to learning, perhaps during
      critical periods of brain development and maturation, or whether they reflect
      innate abilities and capacities that might be fostered by early exposure to music
      is largely unknown. We will report studies that indicate that certain regions in
      the brain (corpus callosum, motor cortex, cerebellum) may show some form of
      adaptation to extraordinary challenges and requirements of performance. These
      challenges may eventually lead to functional and structural cerebral changes to
      accommodate the requirements for musical performance. Furthermore, we will also
      show the neural correlates of one unique musical ability, absolute pitch. This
      ability may be linked to one structure in the human brain (planum temporale),
      which is preferentially activated in musicians who have absolute pitch during
      tone tasks. This structure may undergo some form of functional plasticity that is
      possible only during a critical period of brain development.

PMID- 11458837
TI  - Representational cortex in musicians. Plastic alterations in response to musical
      practice.
AB  - The lifelong ability to adapt to environmental needs is based on the capacity of
      the central nervous system for plastic alterations. In a series of
      neurophysiological experiments, we studied the impact of music and musical
      training in musicians on the specific functional organization in auditory and
      somatosensory representational cortex. In one such study, subjects listened to
      music from which one specific spectral frequency was removed. This led to rapid
      and reversible adaptation of neuronal responses in auditory cortex. Further
      experimental evidence demonstrated that long years of practice and training by
      professional musicians to enable them to reach their capacity is associated with
      enlarged cortical representations in the somatosensory and auditory domains. This
      tuning of neuronal representations was specifically observed for musical tones
      and was absent when pure sinusoidal tones were used as stimuli. In the
      somatosensory cortex, plastic changes proved to be specific for the fingers
      frequently used and stimulated. These changes were not detected in the fingers of
      the hand that were not involved in playing the particular instrument.
      Neuroplastic alterations also may be driven into a domain where they may become
      maladaptive. The clinical syndrome of focal hand dystonia that may occur in
      musicians who engage in forceful practice may be one such consequence. We will
      discuss the possibilities of reversing maladaptive responses leading to the
      successful treatment of focal hand dystonia, which relies on basic research about
      cortical reorganization. This example elucidates how neuroscientific progress can
      guide the development of practice guidelines and therapeutic measures for the
      benefit of professional musicians.

PMID- 11458838
TI  - The brain that plays music and is changed by it.
AB  - Playing a musical instrument demands extensive procedural and motor learning that
      results in plastic reorganization of the human brain. These plastic changes seem
      to include the rapid unmasking of existing connections and the establishment of
      new ones. Therefore, both functional and structural changes take place in the
      brain of instrumentalists as they learn to cope with the demands of their
      activity. Neuroimaging techniques allow documentation of these plastic changes in
      the human brain. These plastic changes are fundamental to the accomplishment of
      skillful playing, but they pose a risk for the development of motor control
      dysfunctions that may give rise to overuse syndromes and focal, task-specific
      dystonia.

PMID- 11458839
TI  - Cortical plasticity and music.
AB  - Auditory experience changes the make-up of areas in the cerebral cortex that are
      involved in the processing of complex sounds, including music. Evidence for this
      comes from various lines of research. Early blindness results in an expansion of
      auditory-responsive areas in the parietal cortex and a refinement in the
      selectivity of neurons in the auditory cortex. Occipital areas normally used only
      for vision are activated by auditory stimuli in the early blind. This lends
      credibility to the claim that blind individuals have greater musical abilities.
      The cross-modal changes in auditory cortical representations are based on
      activity-dependent modifications of synaptic circuitry. Imagery and anticipation
      of music also lead to activation of the auditory (and frontal) cortex. It is
      conceivable, therefore, that even with mental practice alone we can sharpen our
      musical representations in the cerebral cortex.

PMID- 11458840
TI  - The sounds of poetry viewed as music.
AB  - An extended parallel is developed between musical and prosodic structures, using
      the author's cognitively oriented music theory and recent work in generative
      phonology. For illustration, the sounds of a short poem by Robert Frost are
      treated entirely in musical terms. The poem is assigned a phonological stress
      grid and then musical grouping and meter. These structures enable a durational
      realization. Phonological stress also helps assign the poem's normative melodic
      contour. Finally, the similarities and differences in sound repetition are given
      hierarchical structure by means of musical prolongational theory. These formal
      parallels suggest a corresponding realization in brain localization and function.
      Evidence from the neuropsychological literature is cited in support of this view.
      The picture emerges that grouping, meter, duration, contour, and timbral
      similarity are mind/brain systems shared by music and language, whereas
      linguistic syntax and semantics and musical pitch relations are systems not
      shared by the two domains.

PMID- 11458841
TI  - Music and nonmusical abilities.
AB  - Reports that exposure to music causes benefits in nonmusical domains have
      received widespread attention in the mainstream media. Such reports have also
      influenced public policy. The so-called "Mozart effect" actually refers to two
      relatively distinct phenomena. One concerns short-term increases in spatial
      abilities that are said to occur from listening to music composed by Mozart. The
      other refers to the possibility that formal training in music yields nonmusical
      benefits. A review of the relevant findings indicates that the short-term effect
      is small and unreliable. Moreover, when it is evident, it can be explained by
      between-condition differences in the listener's mood or levels of cognitive
      arousal. By contrast, the effect of music lessons on nonmusical aspects of
      cognitive development is still an open question. Several studies have reported
      positive associations between formal music lessons and abilities in nonmusical
      (e.g., linguistic, mathematical, and spatial) domains. Nonetheless, compelling
      evidence for a causal link remains elusive.

PMID- 11458842
TI  - Are music and language homologues?

PMID- 11458843
TI  - Ambiguous musical figures. Sequential grouping by common pitch and sound-source
      location versus simultaneous grouping by temporal synchrony.

PMID- 11458844
TI  - Explaining harmony. The roles of interval dissonance and chordal tension.

PMID- 11458845
TI  - Associations and dissociations among music training, tonal and temporal order
      processing, and cognitive skills.

PMID- 11458846
TI  - Playing the piano by heart. From behavior to cognition.

PMID- 11458847
TI  - Absolute pitch, early musical instruction, and spatial abilities.
AB  - The results of the study show that AP possessors performed better in the Hidden
      Figure Test than did NMs and musicians with RP and that age at which music
      instruction is initiated affects performance in specific spatial tasks.
      Individuals who begin extensive musical instruction at a very early age may have
      an advantage when completing selected spatial tests over those with no formal
      musical training. However, characteristics other than starting age of musical
      instruction are associated with AP and seem to affect musicians' performance in
      the Hidden Figure Test. The differences found between the performance of AP
      possessors and RP possessors in this nonmusical task suggest further research.

PMID- 11458848
TI  - Infant long-term memory for music.

PMID- 11458849
TI  - Phases in children's rhythmic development.

PMID- 11458850
TI  - Variance decomposition of tempo drift in isochronous rhythmic tapping.
AB  - The statistical techniques developed herein show strong promise as a
      nonparametric extension of the classical Wing-Kristofferson decomposition of
      variance in isochronous tapping to include tempo drift. It is now important to
      establish the relative role of the three sources of variance in discriminating
      among unselected individuals as well as selected populations differentiated by
      such factors as age, gender, and motor control impairment. We are currently
      making the estimation techniques available through the web, so that they can be
      applied to extant and new data. We can be contacted by e-mail for further
      information.

PMID- 11458851
TI  - Effects of music perception and imagery on sensorimotor synchronization with
      complex timing patterns.

PMID- 11458852
TI  - Estimates of sequence acceleration and deceleration support the synchronization
      of internal rhythms.

PMID- 11458853
TI  - Frontal lobe contributions to perception of rhythmic group structure. An EEG
      investigation.

PMID- 11458854
TI  - Cortical representations of temporal structures in music.

PMID- 11458855
TI  - Neapolitan chords activate the area of Broca. A magnetoencephalographic study.

PMID- 11458856
TI  - Cortical dynamics and the perception of tone sequence structure.

PMID- 11458857
TI  - On practice: how the brain connects piano keys and piano sounds.

PMID- 11458858
TI  - Electrical brain activity associated with automatic and controlled processing of
      melodic contour and interval.

PMID- 11458859
TI  - Is music an evolutionary adaptation?
AB  - In contemplating the function and origin of music, a number of scholars have
      considered whether music might be an evolutionary adaptation. This article
      reviews the basic arguments related to evolutionary claims for music. Although
      evolutionary theories about music remain wholly speculative, musical behaviors
      satisfy a number of basic conditions, which suggests that there is indeed merit
      in pursuing possible evolutionary accounts.

PMID- 11458860
TI  - Transcranial magnetic stimulation produces speech arrest but not song arrest.

PMID- 11458861
TI  - Development of the happy-sad distinction in music appreciation. Does tempo emerge
      earlier than mode?

PMID- 11458862
TI  - Frontal EEG responses as a function of affective musical features.

PMID- 11458863
TI  - Musical processing in high functioning children with autism.

PMID- 11458864
TI  - Impact of music therapy on the communication skills of toddlers with pervasive
      developmental disorder.

PMID- 11458865
TI  - Music and testosterone. A new hypothesis for the origin and function of music.

PMID- 11458866
TI  - A dynamic systems model of musically induced emotions. Physiological and self
      report evidence.

PMID- 11458867
TI  - Similarity, invariance, and musical variation.
AB  - Perceptual similarity underlies a number of important psychological properties of
      musical materials, including perceptual invariance under transformation,
      categorization, recognition, and the sense of familiarity. Mental processes
      involved in the perception of musical similarity may be an integral part of the
      functional logic of music composition and thus underly important aspects of
      musical experience. How much and in what ways can musical materials be varied and
      still be considered as perceptually related or as belonging to the same category?
      The notions of musical material, musical variation, perceptual similarity and
      invariance, and form-bearing dimensions are considered in this light. Recent work
      on similarity perception has demonstrated that the transformation space for a
      given musical material is limited by several factors ranging from degree of match
      of the values of auditory attributes of the events composing the sequences to
      their relations of various levels of abstraction and to the degree that the
      transformation respects the grammar of the musical system within which the
      material was composed. These notions and results are considered in the light of
      future directions of research, particularly concerning the role of similarity and
      invariance in the understanding of musical form during listening.

PMID- 11458868
TI  - Tonal cognition.
AB  - This article presents a self-organizing map (SOM) neural network model of
      tonality based on experimentally quantified tonal hierarchies. A toroidal
      representation of key distances is recovered in which keys are located near their
      neighbors on the circle of fifths, and both parallel and relative major/minor key
      pairs are proximal. The map is used to represent dynamic changes in the sense of
      key as cues to key become more or less clear and modulations occur. Two models,
      one using tone distributions and the other using tone transitions, are proposed
      for key-finding. The tone transition model takes both pitch and temporal distance
      between tones into account. Both models produce results highly comparable to
      those of musically trained listeners, who performed a probe tone task for ten
      nine-chord sequences. A distributed mapping of tonality is used to visualize
      activation patterns that change over time. The location and spread of this
      activation pattern is similar for experimental results and the key-finding model.

PMID- 11458869
TI  - Neurobiological foundations for the theory of harmony in western tonal music.
AB  - Basic principles of the theory of harmony reflect physiological and anatomical
      properties of the auditory nervous system and related cognitive systems. This
      hypothesis is motivated by observations from several different disciplines,
      including ethnomusicology, developmental psychology, and animal behavior. Over
      the past several years, we and our colleagues have been investigating the
      vertical dimension of harmony from the perspective of neurobiology using
      physiological, psychoacoustic, and neurological methods. Properties of the
      auditory system that govern harmony perception include (1) the capacity of
      peripheral auditory neurons to encode temporal regularities in acoustic fine
      structure and (2) the differential tuning of many neurons throughout the auditory
      system to a narrow range of frequencies in the audible spectrum. Biologically
      determined limits on these properties constrain the range of notes used in music
      throughout the world and the way notes are combined to form intervals and chords
      in popular Western music. When a harmonic interval is played, neurons throughout
      the auditory system that are sensitive to one or more frequencies (partials)
      contained in the interval respond by firing action potentials. For consonant
      intervals, the fine timing of auditory nerve fiber responses contains strong
      representations of harmonically related pitches implied by the interval (e.g.,
      Rameau's fundamental bass) in addition to the pitches of notes actually present
      in the interval. Moreover, all or most of the partials can be resolved by finely
      tuned neurons throughout the auditory system. By contrast, dissonant intervals
      evoke auditory nerve fiber activity that does not contain strong representations
      of constituent notes or related bass notes. Furthermore, many partials are too
      close together to be resolved. Consequently, they interfere with one another,
      cause coarse fluctuations in the firing of peripheral and central auditory
      neurons, and give rise to perception of roughness and dissonance. The effects of
      auditory cortex lesions on the perception of consonance, pitch, and roughness,
      combined with a critical reappraisal of published psychoacoustic data on the
      relationship between consonance and roughness, lead us to conclude that
      consonance is first and foremost a function of the pitch relationships among
      notes. Harmony in the vertical dimension is a positive phenomenon, not just a
      negative phenomenon that depends on the absence of roughness--a view currently
      held by many psychologists, musicologists, and physiologists.

PMID- 11458870
TI  - HCFA and expanded coverage of PET.

PMID- 11458871
TI  - Hybrid imaging in nuclear medicine: continuing innovation in form and function.

PMID- 11458872
TI  - How to renew an NRC license: practical pointers for medical licensees Part 1.

PMID- 11458873
TI  - 'Coupled motions' in cervical spine rotation can be misleading. Comment on V.
      Feipel, B. Rondelet, J.-P. Le Pallec and M. Rooze. Normal global motion of the
      cervical spine: an electrogoniometric study. Clin. Biomechanics 1999; 14: 462
      470.

PMID- 11458874
TI  - New NIH imaging institute established; grassroots support solicited.

PMID- 11458875
TI  - How to renew an NRC license: practical pointer for medical licensees. Part 2.

PMID- 11458876
TI  - The problem of dose-response and therapeutic ratio of inhaled steroids.

PMID- 11458878
TI  - [Abstracts of the All-Russian Symposium on Cell Biology on the Threshold of the
      21st Century. St. Petersburg, October 17-19, 2000].

PMID- 11458879
TI  - Harmonization of vascular surgical training in Europe. A task for the European
      board of vascular surgery (EBVS), (cardiovascular surgery 2000; 8: 98-103).

PMID- 11458880
TI  - Dysregulation of the cytokine network in the uterus of the diabetic rat.
AB  - Insulin-dependent (type I) diabetes is an auto-immune disorder that produces
      secondary complications in numerous non-immunological systems. Changes in the
      synthesis and action pattern of several cytokines have been associated with the
      development of these alterations. Based on the clinical facts that the pregnant
      and non-pregnant functions of the reproductive system are also disrupted by
      diabetes, our laboratory has decided to concentrate its research activities on
      the hypothesis that cytokines may be implicated in the uteropathy and embryopathy
      associated with the metabolic disorder. This review article summarizes our major
      findings concerning the synthesis of TNF-alpha and IL-1beta in the uterus of
      diabetic rats, and in cultures of rodent uterine cells upon their exposure to
      high concentrations of glucose. The paper also reviews evidence that both the
      peri-implanting embryo and the epithelial cell layer lining the uterine lumen are
      targets for the deleterious influence of excess TNF-alpha. If confirmed in the
      uterus of diabetic patients, these observations may explain how cytokines
      contribute to the dysregulation of crucial reproductive events like menstruation
      and embryo implantation in humans.

PMID- 11458881
TI  - Mammalian expression cloning of two human trophoblast suppressors of major
      histocompatibility complex genes.
AB  - PROBLEM: Human trophoblasts suppress interferon-gamma (IFN-gamma)-simulated
      expression of major histocompatibility complex (MHC) class II genes and thereby
      protect the conceptus from maternal immune attack. The mechanism of this
      suppression is poorly understood. METHOD OF STUDY: IFN-gamma-responsive HeLa
      cells were stably transfected with trophoblast cDNA expression libraries and
      screened by negative immunoselection with an antibody to HLA-DR. RESULTS: Two
      suppressor cDNAs were isolated. One encoded the untranslated RNA trophoblast STAT
      utron (TSU), which blocked STAT1 nuclear translocation and can theoretically form
      triplex RNA-DNA at the class II transactivator gene promoters. The other encoded
      the N-terminal 28 residues of chorionic somatomammotropin (hCS). TSU-related
      genes were detected in human and macaque but not in mouse, genomic DNA.
      CONCLUSIONS: The genetics of two human trophoblast MHC suppressors suggest that
      these functions have been gained in human placenta in recent evolutionary
      history. TSU and hCS play critical roles in suppression of MHC genes, which may
      lead to silencing by DNA methylation.

PMID- 11458882
TI  - Subcellular mechanisms of area postrema activation.

PMID- 11458883
TI  - Multisynaptic neuronal pathways from the submandibular and sublingual glands to
      the lamina terminalis in the rat: a model for the role of the lamina terminalis
      in the control of osmo- and thermoregulatory behavior.

PMID- 11458884
TI  - Axonal projections from the organum vasculosum lamina terminalis to the
      supraoptic nucleus: functional analysis and presynaptic modulation.

PMID- 11458885
TI  - Membrane properties of subfornical organ neutrons.

PMID- 11458886
TI  - Role of circumventricular organs in pro-inflammatory cytokine-induced activation
      of the hypothalamic-pituitary-adrenal axis.

PMID- 11458887
TI  - Role of circumventricular organs (CVO) in neuroendocrine responses: interactions
      of CVO and the magnocellular neuroendocrine system in different reproductive
      states.

PMID- 11458888
TI  - Approaches for gene delivery to the subfornical organ and magnocellular neurons.

PMID- 11458889
TI  - Leptin receptors in hypothalamus and circumventricular organs.

PMID- 11458890
TI  - For and against: Public health does not need to be led by doctors. Against.

PMID- 11458891
TI  - GMC: approaching the abyss. Preservation is well worth the effort.

PMID- 11458892
TI  - GMC: approaching the abyss. People should be wary of the alternative.

PMID- 11458893
TI  - GMC: approaching the abyss. GMC: keeping feet on firm ground.

PMID- 11458894
TI  - GMC: approaching the abyss. Time to go.

PMID- 11458895
TI  - GMC: approaching the abyss. Australia may show way foward for the United Kingdom.

PMID- 11458896
TI  - Assessing clinical competence and revalidation of clinicians. Video assessments
      might be effective screening method.

PMID- 11458897
TI  - Assessing clinical competence and revalidation of clinicians. Simulated surgeries
      would have advantages.

PMID- 11458898
TI  - Assessing clinical competence and revalidation of clinicians. Results from pilot
      study using portfolio and 360 degrees questionnaire.

PMID- 11458899
TI  - GMC's guidance may inhibit research.

PMID- 11458900
TI  - Optimising management of delirium. Patients with delirium should be treated with
      care.

PMID- 11458901
TI  - Optimising management of delirium. Placebo controlled trials of pharmacological
      treatments are needed.

PMID- 11458902
TI  - Optimising management of delirium. Withdrawal of Droleptan (droperidol).

PMID- 11458903
TI  - Animal research. Journal editors could help raise profile of three Rs of animal
      research.

PMID- 11458904
TI  - Animal research. Ethics committees have influenced animal experiments in Sweden.

PMID- 11458905
TI  - Animal research. Three Rs should be registration randomisation, and reviews
      (systematic).

PMID- 11458906
TI  - Animal research. Would middle ground approach give "added value"?

PMID- 11458907
TI  - Animal research. More funding must go towards finding alternative non-animal
      methods.

PMID- 11458908
TI  - Wyeth responds to news story on oral contraceptives and DVT.

PMID- 11458909
TI  - C reactive protein and acute phase of ischaemic stroke.

PMID- 11458910
TI  - What's in a name? To be medicine for the elderly, or not to be.

PMID- 11458911
TI  - What's in a name? Tautology, or not tautology.

PMID- 11458912
TI  - Surgeon General releases first installment of a national strategy for suicide
      prevention.

PMID- 11458914
TI  - Andrew Weil, MD on integrative medicine and the nature of reality. Interview by
      Bonnie Horrigan.

PMID- 11458913
TI  - HCFA issues rules on restraints with amendments to ease staffing requirements.

PMID- 11458915
TI  - Use of local exhaust ventilation to control aerosol exposures resulting from the
      use of a reciprocating saw during autopsy.

PMID- 11458916
TI  - Exposure to crystalline silica during a foundry ladle relining process.

PMID- 11458917
TI  - Fire fighting hazards during propane tank fires.

PMID- 11458918
TI  - An ergonomic evaluation of excavating operations: a pilot study.

PMID- 11458919
TI  - The use of 3M porous polymer extraction discs in assessing protective clothing
      chemical permeation.
AB  - The aim of the study was to assess the use of 3M porous polymer extraction discs
      (3M Empore sorbent filters) for detection of chemical permeation of protective
      clothing. Analysis of some commonly used solvents on 3M Empore sorbent filters
      was performed for methanol, acetone, trichloroethylene (TriCE), and toluene by
      solvent desorption and gas chromatography. All solvents exhibited >98 percent
      adsorption on the filters at a spiking level of 1.8 microL for each solvent.
      Solvent recovery for the system was calculated for each solvent, ranging from 72
      94 percent (RSD < or = 4.0%) for all solvents over the spiking range 0.2-1.8
      microL. The modified ASTM F739 method was used to determine breakthrough times
      for five protective glove materials (polyvinyl chloride, natural rubber,
      polymerized alkene, nitrile, and nitrile butyl rubber) using the model solvents
      as test chemicals. Breakthrough times for each type of protective glove were
      determined, and found to range from 36 s to 9 min for acetone, from 142 s to 52
      min for methanol, from 18 s to 12 min for TriCE, and from 32 s to 28 min for
      toluene. The quantitative mass of the solvents on the filters at the time of
      breakthrough detection ranged from 150-159, 157-166, 570-581, and 371-382
      microg/cm2 for acetone, methanol, TriCE, and toluene, respectively. The sorbent
      filter should find utility in collecting chemical permeation samples through
      protective gloves in both laboratory and field studies for quantitative analysis.

PMID- 11458920
TI  - Biological monitoring of n-hexane exposure in Portuguese shoe manufacturing
      workers.
AB  - Occupational risk of exposure to organic solvents concerned many shoe
      manufacturing workers. The most common organic solvents found in workplace
      environments were n-hexane and others hexane isomers. The aim of this study was
      to evaluate the exposure of shoe manufacturing workers to n-hexane, with 2,5
      hexanedione in urine (2,5HD) as a biomarker and to investigate effect in 2,5 HD
      excretion of the co-exposure to other organic solvents. Post-shift urine samples
      from workers who performed gluing tasks (n = 45) in five shoe manufacturers were
      collected, as well as urine samples from a similar number of unexposed controls
      (n = 51) in the same factories. 2,5 HD was measured by capillary gas
      chromatography. Air monitoring of organic solvents in the workplaces was
      performed and the compounds were analyzed by gas chromatography. Significant more
      2,5 HD was found in the urine of personnel who performed gluing tasks than in the
      unexposed workers. A significant correlation was observed between n-hexane
      exposure and urinary 2,5 HD, with a high correlation coefficient. Multiple
      regression analysis indicated that n-hexane exposure and co-exposure to others
      solvents were significant predictors of the concentration of 2,5 HD. Co-exposure
      led to higher urinary 2,5 HD concentrations. The significant effect of co
      exposure reinforces the interest of biological monitoring for n-hexane exposure
      evaluation. In case of multiple exposures, biological monitoring can be a better
      predictive measurement for early detection of n-hexane neurotoxic lesions than
      air monitoring data.

PMID- 11458921
TI  - Recent risk rates of occupational fatalities, injuries, and illnesses in U.S.
      industries and their use in planning environmental controls.
AB  - Cost/benefit justifications are now required for new environmental regulations.
      The benefit is related to the difference between the currently existing health
      risk rate and the rate corresponding to the proposed permissible exposure limit.
      The adoption of many permissible exposure limits has been delayed by the lack of
      supporting human data and the use of animal data instead. This has resulted in
      difficulties and controversies not likely to be resolved soon. Meanwhile, a
      review of currently existing occupational risk rates can provide a perspective
      for best use of available funds. Tables and text are presented summarizing
      published occupational risk data for 1996. Transportation incidents cause 42
      percent of occupational fatalities. Proper selection and training of workers and
      proper work rules should be cost-effective, also especially in other listed
      dangerous industries. Annual risk rates per hundred workers for occupational
      nonfatal injuries and illness were surprisingly high: for manufacturing 10.6, and
      for the entire private sector, 7.4. Seven worst industries ranged from 25.8 to
      30.3. The benefit from controlling such high rates is almost the same whether the
      final rate is 10(-3) or 10(-6). Thus, specifying a good low-cost procedure that
      reduces most of the initial risk can provide the lowest cost/benefit ratio,
      eligible for priority use of available funds.

PMID- 11458922
TI  - Lognormal model for determining dose-response curves from epidemiological data
      and for health risk assessment.
AB  - A practical method is proposed for determining human dose-response curves based
      on reasonable assumptions and simplifications. The epidemiological data needed
      are the fractions of the population suffering an adverse response from exposures
      to two or more patterns of fluctuating concentrations of a pollutant, and the
      statistical parameters of each pattern. The method calculates the two parameters
      of the threshold type dose-response curve of the pollutant, represented by a
      cumulative lognormal distribution. This distribution was derived from a
      reasonable statistical model. The calculation does not require any arbitrary
      safety factors and yields central values. The dose-response parameters then may
      be used to calculate the health risk rate of exposure to any other fluctuating
      concentration pattern. Another method is proposed to select appropriate threshold
      limit values (TLVs) using calculations involving these parameters. Examples are
      given to illustrate the calculations. Results with hypothetical data gave
      apparently reasonable results. They showed the importance not only of the
      geometric mean concentration but also of the geometric standard deviations of
      both the concentrations and of the dose-response curve, that greatly influence
      the results. It is believed that results of useful accuracy should be obtained.
      Health risk rates are readily understood. They are useful for cost-benefit
      calculations. Relative rates can be used to compare the hazards of different
      operations and different plants. The method may make possible the development of
      standards specifying maximum allowable risk rates.

PMID- 11458923
TI  - Injury surveillance in construction: eye injuries.
AB  - Occupational eye injuries are both common and preventable. About 20% of
      occupational eye injuries occur in construction. To investigate the nature of eye
      injuries among construction workers, we analyzed a large data set of construction
      worker injuries. In addition, we interviewed 62 workers with eye injuries to
      further explore circumstances of eye injury and workers' attitudes and behavior
      toward the use of eye protection. Eleven percent (363 cases) of the 3,390
      construction workers in our data set were treated for eye injuries. Welders,
      plumbers, insulators, painters/glaziers, supervisors, and electricians had a
      higher proportion of all injuries due to eye injuries than other trades. Nearly
      half of the diagnoses were abrasions (46%) followed by foreign objects or splash
      in the eye (29%), conjunctivitis (10%), and burns (5%). In the interviews with 62
      workers, we found that employers very frequently required eye protection for all
      tasks or for high-risk tasks, and workers report wearing eye protection
      regularly. However, most did not wear eye protection with top and side shields;
      if we believe the injuries occurred because a particle or liquid passed between
      the glasses and the workers' faces, increased use of goggles or full shields
      would have prevented two-thirds of this group of injuries.

PMID- 11458924
TI  - The performance of personal inhalable dust samplers in wood-products industry
      facilities.
AB  - Recent guidelines for particulate matter and aerosol measurements in the
      workplace describe sampling criteria for three progressively finer particle-size
      selective fractions: inhalable, thoracic, and respirable. For substances like
      wood dust, for which health concerns usually center on particles that enter and
      deposit within the nasal passages, the inhalable fraction, which by definition
      includes particles ranging from 0 to 100 microm in diameter, is of greatest
      interest. There are a variety of commercially available personal samplers that
      can be used to measure inhalable dust in the workplace. At this time, however,
      most of these samplers have received only limited field testing in wood-products
      facility workplaces. This study compared the performance of three different
      personal inhalable dust samplers and a personal total dust sampler in several
      different wood-products industry facilities. Specifically, the study provided
      information on sampler precision and the relationship between results obtained
      with the various personal samplers. The personal samplers that were evaluated
      were the Institute of Occupational Medicine (IOM), the conical inhalable (CIS),
      and the multi-orifice (7-Hole) inhalable dust samplers and the closed-face filter
      cassette (CFFC) total dust sampler. Study results suggest that the CIS and CFFC
      may be more precise than the IOM and 7-hole samplers. Results also indicate that
      the relative performance of the inhalable samplers as compared to the total dust
      sampler may vary as a function of particle size distribution in the workplace.

PMID- 11458925
TI  - Guess what! Atrichia with papular lesions.

PMID- 11458926
TI  - Guess what! Hypotrichosis congenita of Marie Unna: comment.

PMID- 11458927
TI  - Guess what! Comel-Netherton syndrome.

PMID- 11458928
TI  - Guess what! Hypotrichosis simplex.

PMID- 11458929
TI  - Guess what! Tricho-rhino-phalangeal syndrome type 1.

PMID- 11458930
TI  - Guess what! X-linked dominant chondrodysplasia punctata (Conradi-Hunermann-Happle
      Syndrome).

PMID- 11458931
TI  - Panayiotopoulos syndrome.

PMID- 11458932
TI  - Panayiotopoulos syndrome.

PMID- 11458933
TI  - Panayiotopoulos syndrome.

PMID- 11458934
TI  - Neonatal group B streptococcal infection.

PMID- 11458935
TI  - Central sleep apnoeas in patients with Charcot-Marie-Tooth disease.

PMID- 11458936
TI  - Plasma ascorbic acid in heart disease.

PMID- 11458937
TI  - Cyst rupture during surgery.

PMID- 11458938
TI  - Cyst rupture during surgery.

PMID- 11458939
TI  - Application of cholinesterase inhibitors.

PMID- 11458940
TI  - Chagas' disease.

PMID- 11458941
TI  - Chagas' disease.

PMID- 11458942
TI  - Chagas' disease.

PMID- 11458943
TI  - Queen Margrethe II and mortality in Denmark.

PMID- 11458944
TI  - Queen Margrethe II and mortality in Denmark.

PMID- 11458945
TI  - PPARgamma agonists for intestinal ischaemia.

PMID- 11458946
TI  - Meningococcal disease due to strain W135.

PMID- 11458947
TI  - Implications of prelingual deafness.

PMID- 11458948
TI  - Abstracts of the IXth International Congress of Toxicology. 8-12 July 2001,
      Brisbane, Australia.

PMID- 11458949
TI  - Clonal chromosome aberrations secondary to chromosome instability in an
      elastofibroma.

PMID- 11458950
TI  - Why do multiple deletions accumulate during progression in carcinomas?

PMID- 11458951
TI  - Is this "MDS" or not?

PMID- 11458952
TI  - Abstracts of meetings of the Nutrition Society, 1999-2001.

PMID- 11458953
TI  - GEC-ESTRO annual brachytherapy meeting. Stresa, Italy, 7-9 June 2001. Abstracts.

PMID- 11458954
TI  - Abstracts of the 1st ESTRO (European Society for Therapeutic Radiology and
      Oncology) Workshop on Biology in Radiation Oncology. Fuglso, Denmark, 10-12 June
      2001.

PMID- 11458955
TI  - EUROPACE 2001. Abstracts from the European Working Groups on Cardiac Pacing and
      Arrhythmias. 24-27 June 2001, Copenhagen, Denmark.

PMID- 11458956
TI  - ILAR 2001. Abstracts of the 20th Congress of the International League of
      Associations for Rheumatology. Edmonton, Alberta, Canada. August 26-30, 2001.

PMID- 11458957
TI  - Innovative rheumatology: gene and cell therapies of arthritis and related
      autoimmune disorders 2nd international meeting. Montpellier, France, 17-18 May
      2001. Abstracts.

PMID- 11458958
TI  - Abstracts of the 1st International WASOG Conference on Diffuse Lung Diseases and
      the 7th Conference of the Italian Chapter of WASOG (World Association of
      Sarcoidosis and Other Granulomatous Disorders). June 7-9, 2001. Venice Lido,
      Italy.

PMID- 11458959
TI  - Abstracts of the 10th European Congress of Clinical Microbiology and Infectious
      Diseases. Stockholm, Sweden, 28-31 May 2000.

PMID- 11458960
TI  - [Index of scientific publication: description and results].

PMID- 11458961
TI  - Determination of the pK(a) of 12-S-hydroxyheptadecatrienoic acid by studies of
      its vial surface adsorption using high-performance liquid chromatography and
      liquid scintillation technique.
AB  - When dissolving 12-S-hydroxyheptadecatrienoic acid (HHT) in aqueous buffer
      systems, a partition equilibrium is achieved between the liquid buffer phase and
      the solid vial phase. This adsorption equilibrium is dependent on the vial
      material, the ratio of solvent volume to moistened vial surface area (V/A), the
      pH of the aqueous solution the buffer additives and the contact time. Partition
      ratios (E) were established following determination of the recoveries (omega) of
      HHT in the liquid phases. The pK(a) of HHT could be calculated to be 4.4 +/- 0.2.
      The HHT concentration in the liquid phase rose considerably when increasing the
      pH value (17% at pH 1.9, up to 97% of applied HHT at pH 8.0) and increasing the
      V/A-ratio, as well as when using glass instead of polypropylene (PP) or adding
      acetonitrile as an organic solvent and HHT-affine substances like albumins or
      globulin. The HHT concentration was found to decrease during contact to PP
      surfaces as a result of HHT adsorption and diffusion into the hydrophobic vial
      material. This effect could be minimized by adding a larger percentage of
      acetonitrile (50-60%).

PMID- 11458962
TI  - Thermodynamic and structural characterization of cis-trans isomerization of 12
      (S)-hydroxy-(5Z, 8E, 10E)-heptadecatrienoic acid by high-performance liquid
      chromatography and gaschromatography-mass spectrometry.
AB  - It is shown that 12-(S)-hydroxy-(5Z, 8E, 10E)-heptadecatrienoic acid (5-cis-HHT)-
      a physiological metabolite of arachidonic acid--is acid-catalyzed converted into
      a less polar substance with its maximum UV-absorption at (1)max=232 nm and a
      molar absorptivity of about epsilon=26600 +/- 200 M(-1)cm(-1). Using a reversed
      phase high-performance liquid chromatographic (HPLC) method this equilibrium
      reaction (K(c) = 1.78 +/- 0.05 at pH 1.10 and 298 K) could be thermodynamicly
      characterized as a pH dependent, exergonic and exothermic reaction according to
      kinetics of a first order reaction (at pH 1.10 and 298 K: delta(R)G(o) = -1.42 +/
      0.07 kJ mol(-1), delta(R)H(o) = -3.50 +/- 0.9 kJ mol(-1), delta(R)S(o) = 7.0 +/-
      3.0 J mol(-1)*K, delta(R)H*f = 100.0 +/- 4.0 kJ mol(-1)). Kinetic data for
      several pH-values and temperatures are presented. These data and structural
      characterization by gaschromatography-mass spectrometry (GC/MS) lead to the
      conclusion that 5-cis-HHT is isomerized to 12-(S)-hydroxy-(5E, 8E, 10E)
      heptadecatrienoic acid (5-trans-HHT).

PMID- 11458963
TI  - Clinical picture: Multicolour karyotyping.

PMID- 11458964
TI  - Ontogeny of behavioral responsiveness to sound in the chick embryo as indicated
      by electrical recordings of motility.
AB  - The primary purpose of these experiments was to gather normative behavioral data
      regarding the ontogeny of responsiveness to sound in the chicken embryo. As a
      prerequisite, a sensitive ane accurate method for recording embryonic motility
      was developed (Experiment 1). By means of platinum electrodes inserted just
      beneath the shell membrane, potentials resulting from heartbeat and movement were
      recorded on a polygraph. The technique was found to be effective when applied to
      chick embryos 6 days and older. Correlations between visual observations of
      activity and the records produced by the electronic technique substantiated its
      accuracy. Behavioral responses of chick embryos (Stages 39-43) to acoustic
      stimulation (Experiment 2) were then recorded. High-intensity (115-dB SPL) tones
      of 400, 700, and 1400 Hz were used as stimuli. The earliest consistent responses
      were recorded from Stage 40 (ca. Days 14-15) subjects; the 700 and 1400 Hz tones
      produced statistically reliable inhibition of movement during the stimulus period
      compared with the post-stimulus period. Reliable increases in movement during the
      stimulus period were first recorded at Stage 42 (ca. Days 16-17) in response to
      700 and 1400 Hz and at Stage 43 (ca. Days 17-18) in response to 400 Hz.

PMID- 11458965
TI  - Prospective study of the natural history of infectious mononucleosis caused by
      Epstein-Barr virus.
AB  - BACKGROUND: Knowledge regarding the clinical characteristics and natural history
      of acute infectious mononucleosis is based largely on older, often retrospective,
      studies without systematic follow-up. Differences in diagnosis, methodology, or
      treatment between historical and current practice might affect an understanding
      of this illness. METHODS: Using a prospective case series design, we enrolled 150
      persons with an acute illness serologically confirmed as Epstein-Barr virus
      infection. The goal of the study was to assess symptoms, physical examination
      findings, laboratory tests, and functional status measures during the acute
      presentation and 1, 2, and 6 months later. RESULTS: Acutely, infectious
      mononucleosis was characterized by the symptoms of sore throat and fatigue and
      substantial functional impairment. Objective physical and laboratory examination
      findings included pharyngitis and cervical lymphadenopathy, a moderate absolute
      and atypical lymphocytosis, and mildly elevated transaminase levels. The
      traditional signs of fever and splenomegaly were relatively uncommon. By 1 month,
      most symptoms and signs and all laboratory tests had returned to normal. Fatigue,
      cervical lymphadenopathy, pharyngitis, and functional health status improved more
      slowly. CONCLUSIONS: In contemporary practice most of the classical illness
      features of infectious mononucleosis are observed. Symptoms, signs, and poor
      functioning might be protracted in some patients.

PMID- 11458966
TI  - Diabetes management quality improvement in a family practice residency program.
AB  - BACKGROUND: Diabetes is a devastating chronic disease. Although optimal diabetes
      control reduces chronic complications, actual provision of diabetes care
      frequently falls short of accepted guidelines. We wanted to determine whether
      locally developed diabetes care initiatives can result in improvements in the
      provision of diabetes care. METHODS: This study was a retrospective cohort
      analysis using Medicare claims and chart abstraction data to ascertain diabetes
      care indicator utilization rates at the Northeast Iowa Family Practice Clinic
      (NEIFPC), which serves as the training site for the Northeast Iowa Family
      Practice Residency Program. Diabetic patients receiving care at the NEIFPC during
      1996, 1997, and 1998 were included. Diabetes care rates are compared with those
      of other Iowa practices. Diabetes initiatives included chart audits, glycosylated
      hemoglobin (HbA1c) measurement reminder cards, educational symposia, an
      endocrinology outreach clinic, resident elective rotations, diabetes flow sheet
      utilization, pharmacist interface, and nursing foot-examination preparations. The
      primary outcome was the utilization rate of accepted diabetes care indicators.
      RESULTS: Diabetic patients at NEIFPC had greater utilization of diabetes care
      indicators than did patients of Iowa collaborators in 1997 and 1998. NEIFPC
      patients had HbA1c levels measured more frequently in 1997 and 1998 (84% and 88%,
      respectively) than did patients of Iowa collaborators (49% and 41%, respectively)
      (P < .001). The mean 1997 and 1998 HbA1c levels of 7.32% and 7.25%, respectively,
      are impressive compared with that of Iowa collaborators (8.83% and 8.36%) (P <
      .001) and other published data (8.5%-10%). The percentage of NEIFPC patients with
      good glycemic control (HbA1c < 8%) was 75%, compared with the reported 50% of all
      US patients. CONCLUSIONS: Our findings suggest that multimodal diabetes care
      quality improvement initiatives, applied longitudinally, can result in
      significant improvements in the provision and documentation of diabetes care.

PMID- 11458967
TI  - Domestic violence screening, policies, and procedures in Indian health service
      facilities.
AB  - BACKGROUND: Research shows that domestic violence against women in the United
      States is common, and the prevalence of domestic violence is high among Native
      American women. Victims of domestic violence can benefit from appropriate office
      intervention and referral. This study examined the effect of administrative and
      legal requirements on screening for domestic violence in Indian Health Service
      (IHS) hospitals and clinics. METHODS: A questionnaire was mailed using the total
      design method to all IHS hospitals and clinics regarding activities related to
      domestic violence: screening; policies and procedures; presence of committees;
      staff training; and state and tribal mandatory reporting requirements. RESULTS:
      The response rate was 65%. Eighty-eight (62%) of 142 facilities screen for
      domestic violence. A facility was more likely to screen if it had policies and
      procedures for domestic violence. Ninety-one (64%) of sites had policies and
      procedures for domestic violence. Less than one half these sites evaluated the
      use of these policies and procedures. Hospitals were more likely to have policies
      and procedures than clinics, as were sites administered by the IHS, rather than
      those administered by tribal contract. Fifty-eight (40.8%) facilities indicated
      18 states have mandatory domestic violence reporting requirements. Thirty-three
      (23.2%) facilities indicated 31 different tribes mandate reporting of domestic
      violence. Forty-two (29.6%) facilities reported mandatory staff training in at
      least one topic related to domestic violence in the past year. CONCLUSIONS:
      Domestic violence policies and procedures promote screening for this important
      health care problem.

PMID- 11458968
TI  - Open-access appointment scheduling in family practice: comparison of a demand
      prediction grid with actual appointments.
AB  - BACKGROUND: Inadequate access to their primary care physician remains a major
      reason for patient dissatisfaction in ambulatory care. The concept of open-access
      appointment scheduling has been found to accommodate patients' urgent health care
      needs while providing continuous, routine care. We describe the development of a
      demand prediction grid for future appointments, compare it with one developed by
      Kaiser Permanente, and compare the predictions with actual appointments made and
      held in our clinic. METHODS: Using adjusted 1999 appointments based on historical
      data for the Scott & White Killeen Clinic (> 75,000 annual appointments; 13
      family physicians), we computed appointment predictions for calendar year 2000 by
      day of the week and by month of the year. We then compared our predictions with
      those of Kaiser and actual appointments for the first half of 2000. RESULTS: Our
      data and the Kaiser data agreed on the day of week, but they were different for
      the summer and winter months. Overall, actual appointments made and held at our
      clinic for January through June 2000 were within 6% of the predictions.
      Appointments for January and February were 18% and 4% more than the predictions,
      respectively, while appointments for March were 3% less than the predictions.
      Appointments for April through June were 3% to 7% more than the predictions. Few
      daily variations were observed between actual appointments and predictions.
      CONCLUSIONS: We conclude that the Kaiser data might be tempered by a different
      climate, underscoring the need for each practice to develop its own demand
      prediction grid. That our actual appointments were 6% more than predicted overall
      but fluctuated month by month reemphasizes the need for continuous monitoring of
      the adjustment factor for prediction.

PMID- 11458969
TI  - Hereditary hemochromatosis.
AB  - BACKGROUND: The understanding of hereditary hemochromatosis, along with the
      availability of genetic testing, is changing the approach to diagnosis of the
      disease. METHODS: A MEDLINE search was performed using multiple key words related
      to hemochromatosis and iron metabolism. RESULTS: Most cases of hereditary
      hemochromatosis are caused by a single mutation to the HFE gene, resulting in
      unregulated dietary iron uptake. The signs and symptoms of hereditary
      hemochromatosis are nonspecific and common in family practice settings. Measuring
      the transferrin saturation level is a cost-effective way to screen for suspected
      disease. Subsequent workup includes serum ferritin levels, hepatic enzyme levels,
      and HFE gene testing, or liver biopsy. HFE gene testing can provide a definitive
      diagnosis in many patients. Liver biopsy is useful and indicated when liver
      disease is clinically evident. CONCLUSION: For many patients, hereditary
      hemochromatosis can be diagnosed and treated in the physician's office. After
      iron mobilization with therapeutic phlebotomy, most patients will require
      phlebotomy 2 to 4 times each year throughout their lifetime. Treatment before
      organ toxicity occurs leads to a normal life span. Treatment after symptoms
      appear is less effective but can improve some signs and symptoms of iron
      toxicity.

PMID- 11458970
TI  - Fallopian tube torsion: laparoscopic evaluation and treatment of a rare
      gynecological entity.
AB  - BACKGROUND: Fallopian tube torsion is a cause for acute low abdominal pain that
      is difficult to diagnose. The purpose of this article is to review the available
      data on and to update clinicians regarding its diagnosis and treatment in the era
      of laparoscopic surgery. METHODS: We searched in MEDLINE and EMBASE and reviewed
      the lists of references. The keywords used were "laparoscopy," "fallopian tube,"
      and "torsion." RESULTS AND CONCLUSION: Fallopian tube torsion is an uncommon
      cause for acute low abdominal pain in women. Because it has no pathognomonic
      clinical symptoms or findings on imaging or laboratory studies, a history of
      current or past pelvic pathologic conditions or surgery, as well as pregnancy,
      should draw the attention of the attending physician to its occurrence. Early
      laparoscopy is the reference standard in the diagnosis and treatment.

PMID- 11458971
TI  - Diabetes mellitus associated with atypical antipsychotic medications: new case
      report and review of the literature.
AB  - BACKGROUND: Since the introduction of atypical antipsychotic medications,
      beginning with clozapine in 1990, several case reports in the psychiatric
      literature have suggested that they might be associated with new onset of
      diabetes mellitus as well as with diabetic ketoacidosis. METHODS: We report the
      case of a 38-year-old patient with schizophrenia who suddenly developed diabetes
      mellitus and ketoacidosis 12 months after starting olanzapine. Similar cases in
      the literature were found through a MEDLINE-assisted search using the key words
      "schizophrenia," "diabetes mellitus," "ketoacidosis," and "adverse drug
      reaction." RESULTS: Including this case, 30 patients have been reported in the
      literature to have developed diabetes or have lost diabetic control after
      starting clozapine, olanzapine, or quetiapine. Twelve of these 30 developed
      diabetic ketoacidosis. Two limited quantitative studies have added evidence
      toward this association. CONCLUSION: Although a causal relation has not been
      definitively proved, the number of cases reported in the literature suggests
      there might be an association between atypical antipsychotic medications and
      diabetes mellitus. Primary care physicians who care for patients with
      schizophrenia should be aware of this possible association.

PMID- 11458972
TI  - Treatment of AIDS and HIV-related conditions: 2001.

PMID- 11458973
TI  - Fat embolism syndrome in a surgical patient.

PMID- 11458974
TI  - Scurvy: an unusual cause of anemia.

PMID- 11458975
TI  - Reset osmostat in a 47-year-old woman with cerebral palsy.

PMID- 11458976
TI  - Improving diabetes care: organize your office, intensify your care.

PMID- 11458977
TI  - Breast-feeding education.

PMID- 11458978
TI  - In vivo induction of hepatic p-glycoprotein by cyclosporine in the rat.
AB  - The objective of the present study was to investigate the regulation of P
      glycoprotein by cyclosporine, a known inhibitor of CYP3A, at different dosage
      levels and lengths of treatment. Rats were given various doses of cyclosporine
      through oral administration or subcutaneous injection. Each treatment group was
      studied for 28 days or 28 days followed by 14 days of olive oil vehicle dosing.
      In each group, rats administered vehicle alone served as the controls. At the end
      of the study, liver microsomes were prepared and hepatic P-glycoprotein levels
      were quantified by Western blot analysis. Significant induction of hepatic P
      glycoprotein was found in rats given cyclosporine. Rats administered 30 mg/Kg/d
      orally and 15 mg/Kg/d subcutaneously showed an increase in hepatic P-glycoprotein
      by 93% (p = 0.0011) and 136% (p < 0.001), respectively. Low doses of cyclosporine
      also induced P-glycoprotein but not to a significant extent, indicating a dose
      dependent effect. The pattern of induction of P-glycoprotein was not, however,
      dependent on the route of administration. Fourteen days after the discontinuation
      of cyclosporine treatment, P-glycoprotein levels returned to near the control
      values. As a drug efflux transporter, the induction of P-glycoprotein by
      cyclosporine may decrease the hepatic metabolism of P-glycoprotein substrates.
      Therefore this induction of hepatic P-glycoprotein and suppression of hepatic
      CYP3A may have a coordinate effect on the metabolism of cyclosporine. These data
      may help explain the large variability associated with cyclosporine absorption,
      metabolism, and circulating blood levels.

PMID- 11458979
TI  - Immunoglobulin G subclass distribution of autoantibodies to gangliosides in
      patients with Guillain-Barre syndrome.
AB  - IgG anti-ganglioside antibodies are present in a proportion of patients with the
      Guillain-Barre syndrome (GBS). To determine if antibodies to gangliosides are
      restricted in IgG subclass distribution, we evaluated IgG subclass antibody
      responses to gangliosides in sera of patients with GBS. Sera from GBS patients
      with IgG activity against gangliosides were analyzed for IgG subclass
      distribution using an enzyme-linked immunosorbent assay. The anti-LM1 antibodies
      in sera from GBS patients were predominantly of the IgG3 subclass while anti-GM1
      and anti-GT1a antibodies were predominantly of the IgG1 and IgG3 subclasses. The
      results indicate a Th2-dependent antibody response.

PMID- 11458980
TI  - Immunomodulatory effects of etanercept (TNFR:Fc) and its use in a patient with
      Crohn's disease.
AB  - Designer drug etanercept (TNFR:Fc) is an inhibitor of TNF-alpha that binds with
      greater affinity than membrane receptors. Its full immunomodulatory effects are
      unknown. Approved for rheumatoid arthritis, its therapeutic potential in Crohn's
      disease has yet to be explored. We describe the course of a steroid-dependent
      patient with Crohn's disease given etanercept, and its effects on cytokine
      protein and mRNA expression and transcription factor activity in human
      leukocytes. Etanercept 25 mg s.c., was given twice weekly for 1 month. Weekly
      ESR, disease activity index, prednisone requirement, and serum cytokines were
      determined. In vitro, effects of physiologic concentrations of etanercept on
      cytokine protein and mRNA, and NFKB and GR transcription factor activity, were
      determined using MOT and U937 cell lines and peripheral blood mononuclear cells.
      Rapid clinical, biochemical, and immunologic improvement occurred, but
      obstruction due to stricture developed after 4 weeks. In vitro, constitutive and
      stimulated production of TNF-beta, IL-1beta, MIP-1beta, and IL-8 by normal
      mononuclear cells declined with etanercept, detectable TNF-alpha increased. MOT
      TNF-alpha expression tripled, mRNA for IL-12 p40 doubled, GR activity declined in
      U937 cells, NFKB was unaffected. Etanercept has complex immunomodulatory effects,
      and may be useful in Crohn's disease, but acutely decreased inflammation could
      worsen stricture.

PMID- 11458981
TI  - The association between postmenopausal vertebral bone mineral density and
      estrogen receptor gene alleles in ethnic Japanese living in western Japan.
AB  - Bone mass and its mineral content has been shown to be under genetic control. Our
      purpose in this study was to assess whether estrogen receptor genotypes influence
      changes in bone mass in post menopausal Japanese women and clarify the regional
      differences in Japanese women. Pvu II and Xba I restriction enzyme fragment
      length polymorphism of the estrogen receptor gene and its relationship with
      vertebral bone mineral density were examined in 300 unrelated post menopausal
      women, aged 42-69 years, from the Kinki region in Japan. Vertebral bone mineral
      density was evaluated at the lumbar spine (L2-4) by dual energy X-ray
      absorptiometry. We found no relationship between any single restriction site
      polymorphism and the Z-score of bone mineral density. However, the allelic
      haplotype PPXx was found to be associated with a significantly low bone mineral
      density (Z-score for the lumbar spine -1.118+/-1.270 vs. PPxx 0.04+/-1.150;
      p<0.01, vs. ppxx 0.387+/-1.226; p<0.05, respectively). We suggest that ER gene
      polymorphism is associated with low bone mineral density and that this partly
      explains the cause of post menopausal bone loss in Japanese women. The
      contradictory conclusions compared with previous studies in the Japanese
      population regarding the association of BMD with ER RFLPs demands further
      investigation.

PMID- 11458982
TI  - P53 codon 72 genotypes in colon cancer. Association with human papillomavirus
      infection.
AB  - It has been reported that the p53Arg homozygous genotype could be a potential
      genetic risk factor for cancer. In this study we investigated the proportion of
      p53 codon 72 genotypes in patients with colon cancer and compared to a control
      population. A region of the p53 gene containing the polymorphic site was
      amplified by PCR and the genotypes were determined by restriction enzyme
      digestion. No significant difference was found between genotype frequencies in
      the study groups. Infection with human papilloma virus was also investigated in
      the tumor samples. HPV 18 and HPV 33 infection was observed in a considerable
      number of the tumor samples. Incidence of HPV infection did not show a
      correlation with the genotypes. Thus the p53 genotypes do not seem to be
      associated with risk of colon cancer or HPV infection.

PMID- 11458983
TI  - Does the estrogen receptor gene polymorphism relate to undefined menopausal
      symptoms?
AB  - The present study examines the relationship between estrogen receptor (ER) gene
      polymorphism and undefined complaints to clarify the aging process of the
      genitospinal center. Pvu II and Xba I restriction fragment length polymorphism
      (RFLP) of the estrogen receptor (ER) gene and its relationships to undefined
      symptoms was examined in 507 Japanese peri- and postmenopausal women who were
      classified in 3 groups by serum estradiol (E2) values; group A:E2>30 pg/ml; group
      B:E210-30 pg/ml; group C:E2<10 pg/ml. The percentage of women grouped A was
      significantly higher than that of group B in genotype Pp. Furthermore, the
      frequency of Ppxx in group A was significantly higher than that of group B or C.
      On the other hand, the frequency of ppxx in group A was significantly lower than
      that of group B (p=0.0042) or C (p=0.049). Neither FSH nor LH differed
      significantly between Ppxx and ppxx. On the other hand, the plasma estradiol
      level differed significantly between Ppxx and ppxx (p=0.0004). Moreover, a higher
      incidence of mental symptoms was observed in group A than in groups B or C
      (p<0.01). The present results suggest that ER gene polymorphism influences aging
      of the genitospinal center, and may explain in part the pathophysiology and cause
      of undefined perimenopausal complaints.

PMID- 11458984
TI  - The effect of methyl methanesulfonate (MMS)-induced excision repair on p53
      dependent apoptosis in human lymphoid cells.
AB  - The tumor suppressor p53 product has been shown to play an important role in
      preventing carcinogenesis by at least two different mechanisms, by evoking cell
      cycle arrest and eliciting DNA repair on one hand, or by eliminating damaged
      cells by induction of apoptosis on the other hand. As a first step toward
      understanding the relationship between protective responses and apoptosis after
      genotoxic stress, we examined the effect of DNA strand breaks generated from
      repair processes in respect to acute cellular responses against DNA damage, and
      on p53-dependent apoptosis in human lymphoid cells. We used two isogenic cell
      lines, TK6 harboring wild-type p53, and WI-L2-NS, which carries a mutant p53. A
      significant difference in sensitivity was observed at 50 microg/ml methyl methane
      sulfonate (MMS) between the two cell lines used. In addition, a clear p53
      mediated contribution to apoptosis in MMS-induced cell death was observed.
      However, we did not observe any differences in repair of MMS-lesions, as
      determined by comet assay, between the two cell lines. These data suggest that
      the differences in apoptosis induction in the two lines are not a reflection of
      differences in strand-break frequency or repair capacity.

PMID- 11458985
TI  - Kinetics of testosterone 6beta-hydroxylation in the reconstituted system with
      similar ratios of purified CYP3A4, NADPH-cytochrome p450 oxidoreductase and
      cytochrome B5 to human liver microsomes.
AB  - Kinetics of testosterone 6beta-hydroxylation were determined using a
      reconstituted system that consisted of CYP3A4, cytochrome b5 and NADPH-cytochrome
      P450 oxidoreductase (OR) with similar ratios as those seen in human liver
      microsomes and compared with those determined using human liver microsomes. Two
      reconstituted systems were constructed in accordance with two human liver
      microsomal samples that showed extremely high and low ratios of OR/CYP3A4. The Km
      values of testosterone 6beta-hydroxylation obtained from the reconstituted
      systems with high and low OR/CYP3A4 ratios were 29.3 and 35.2 microM,
      respectively, which were similar to that of the corresponding human liver
      microsomal samples (23.2 and 40.0 microM, respectively). However, Vmax values
      obtained from the reconstituted systems (3.7 and 0.8 pmol/min/pmol CYP3A4) were
      much lower than those from the human liver microsomes (44.2 and 31.1
      pmol/min/pmol CYP3A4). The results suggest that the interaction between substrate
      and CYP3A4 in the reconstituted systems appear to be similar to human liver
      microsomes but that the velocity of the substrate metabolism in the reconstituted
      systems is different from that in human liver microsomes. In conclusion, our
      reconstituted systems could be used for the determination of affinity but not for
      the determination of the maximum velocity of substrate metabolism. Further
      studies on the protein-protein interactions between CYP3A4, OR, cytochrome b5
      and/or a specific lipid environment are required to establish a reconstituted
      system showing similar kinetic properties to those of human liver microsomes.

PMID- 11458986
TI  - Are proinflammatory cytokine concentrations reduced by plasma exchange in
      patients with severe acute hepatic failure?
AB  - We studied citric acid levels and proinflammatory cytokines (TNF-alpha, IL-6, and
      IL-8) before and after plasma exchange in 8 patients with acute liver failure.
      Plasma exchange was performed over a 6 to 7-hour period. At each session, 3.6 to
      4.0 1 of plasma was exchanged for the same volume of fresh frozen plasma (FFP).
      The concentrations of citric acid were significantly increased after plasma
      exchange above concentrations before exchange (p<0.0001). There were no
      significant differences in TNF-alpha, IL-6, or IL-8 concentrations (p=0.7222,
      p=0.9357, p=0.6394, respectively). Thus, plasma exchange with FFP alone may not
      effectively remove cytokines.

PMID- 11458987
TI  - Organ-specific differences in 8-oxoguanosine glycosylase (OGG1) repair following
      acute treatment with benzo[a]pyrene.
AB  - The lung has been shown to be a target organ for the deleterious effects of
      Benzo[a]pyrene (B[a]P), regardless of the route of exposure. 8-hydroxy-2'
      deoxyguanosine (oxo8dG) is a mutagenic lesion formed in DNA following exposure to
      B[a]P. The objective of this study was to determine the capacity of different
      organs to repair oxo8dG following intraperitoneal (i.p.) treatment with B[a]P.
      Male Spraque-Dawley rats were administered 20 mg/kg B[a]P i.p., 2 times/day for 5
      days. A 26% decrease in the capacity to remove oxo8dG was observed in lung tissue
      at 72 hours and recovered 20% above control values at 120 hours. The capacity of
      the liver and kidney remained at baseline for all time points analyzed. A 7-fold
      increase in oxo8dG was observed in the lung at 72 hours. This study demonstrates
      that organ-specific differences exist in the capacity to remove oxo8dG and
      further demonstrates the susceptibility of lung tissue to the effects of B[a]P.

PMID- 11458988
TI  - Wortmannin inhibits platelet aggregation produced by interaction of gamma
      aminobutyric acid and the calcium tonophore, A23187.
AB  - Platelet aggregation by gamma-aminobutyric acid (GABA) agonists combined with a
      calcium ionophore was studied. GABA, baclofen and mucimol markedly amplified
      aggregatory responses to a subthreshold concentration of the ionophore, A23187.
      This effect was inhibited by wortmannin, a blocker of phosphoinositide 3-kinase.
      However, several antagonists of GABA receptors had no effect on the response, and
      benzodiazepines inhibited aggregation. These results suggest that the GABA effect
      is not mediated by traditional neuronal GABA receptors. We propose that
      wortmannin inhibits aggregation at a nexus downstream from membrane mechanisms
      triggered by the GABA-A23187 interaction.

PMID- 11458989
TI  - Effects of endothelin-1 on the myogenic contraction of canine cerebral artery in
      response to quick stretch.
AB  - The present study was performed to investigate the effects of endothelin-1 (ET-1)
      on the myogenic contraction in response to mechanical stimulation in cerebral
      artery. Quick stretch at a rate of 10 cm/sec with the amount of 10 - 40% of the
      initial muscle length (=100%) produced a myogenic contraction in canine cerebral
      artery. ET-1 at 30 pM, which itself produces a small contraction corresponding to
      about 15% of the maximal response, potentiated stretch-induced contraction. By
      contrast, ET-1 at concentrations over 100 pM suppressed the stretch-induced tone.
      The potentiated component of stretch-induced tone in the presence of 30 pM ET-1
      was largely attenuated by Ca2+ channel blockers, nimodipine (1 microM) or
      diltiazem (1 microM). These findings suggest that lower concentrations (pM range)
      of ET- 1 potentiates myogenic tension development of cerebral artery in response
      to mechanical stretch possibly via an increased Ca2+ influx through voltage-gated
      Ca2+ channel.

PMID- 11458990
TI  - The effect of repeated treatment with pramipexole on the central dopamine D3
      system.
AB  - The study examined the effect of pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl
      aminobenzthiazole dihydrochloride; PRA), a new potent dopamine receptor agonist
      with the high preference for D3 receptors, as compared to D2 or D4, on the
      central dopamine D3 system. Experiments were conducted on male Wistar rats. PRA
      was injected subcutaneously. PRA given repeatedly (14 days, twice a day, in doses
      of 0.3 and 1 mg/kg), but not acutely, potentiated the locomotor hyperactivity
      induced by (+/-)-7-OH-DPAT (3mg/kg s.c.), when given 24h after the single or the
      last dose of PRA. Administration of PRA, 1 mg/kg, for 3 or 7 days produced an
      effect similar to that described above, whereas a dose of 0.3 mg/kg produced such
      an effect only after 7, but not 3, days. Repeated treatment with PRA (0.3 and 1
      mg/kg, 14 days, twice daily) also enhanced the D3 receptor binding in the islands
      of Calleja and nucleus accumbens (shell)--the brain region known to be rich in D3
      receptors--when [3H]7-OH-DPAT was used as a ligand. Repeated PRA administration
      did not change the concentration of mRNA coding for D3 receptors in the islands
      of Calleja. The obtained results indicate that-- like the previously studied
      typical antidepressants given repeatedly--PRA increases the functional
      responsiveness and the binding to the brain dopamine D3 receptors. Hence PRA may
      be considered as a potential antidepressant drug.

PMID- 11458991
TI  - D-Amphetamine potentiates muscimol-induced disinhibition of A10 dopaminergic
      neurons in the rat.
AB  - Evidence suggests that sensitisation to the behavioural effects of d-amphetamine
      involves a late-onset (>3 hrs), long-term potentiation (LTP)-like change at
      medial prefrontal cortex (mPFC)-regulated synapses on A10 dopaminergic (DA)
      neurons. Since muscimol-induced excitation of A10 DA neurons is dependent on mPFC
      regulated afferents, this assay was used to assess whether d-amphetamine enhances
      the driving of A10 DA neurons by the mPFC, as would be predicted if it resulted
      in the conditions necessary for LTP. Animals were administered d-amphetamine or
      saline, 3-4.5 hrs prior to recording. In the acute condition, animals were drug
      naive prior to d-amphetamine, whilst in the challenge condition, animals had
      previously received d-amphetamine (or saline) each day for 6 days. Recording took
      place on withdrawal day 2. Muscimol produced significantly less inhibition of A10
      DA neurons from animals administered d-amphetamine (rather than saline), but only
      when d-amphetamine had been chronically administered beforehand (i.e. in the
      challenge condition). Hence, although the studies fail to provide evidence that
      acute d-amphetamine administration produces the conditions necessary for LTP,
      chronic d-amphetamine administration appears to potentiate the impact on A10 DA
      neurons of mPFC-regulated excitatory activity, thus strengthening the link
      between this potentiation and the sensitisation process. KEYWORDS: Ventral
      tegmental area, excitatory amino acids, medial prefrontal cortex, non-DA neurons,
      synaptic plasticity, behavioural sensitisation.

PMID- 11458992
TI  - Lipopolysaccharide administration produces time-dependent and region-specific
      alterations in tryptophan and tyrosine hydroxylase activities in rat brain.
AB  - The present study examined the effect of systemic administration of
      lipopolysaccharide (LPS; 100 and 250 microg/kg, i.p.) on tyrosine hydroxylase
      (TH) and tryptophan hydroxylase (TPH) activities in frontal cortex, striatum and
      midbrain of the rat. Enzyme activities were determined by measuring accumulation
      of the transient intermediates 5-hydroxytrptophan (5-HTP) and L
      dihydroxyphenylalanine (L-DOPA) following in vivo administration of the
      decarboxylase inhibitor, NSD 1015. TPH activity was increased 2 hours after
      administration of LPS (100 and 250 microg/kg) in both frontal cortex and
      midbrain, and a secondary increase was seen in the midbrain 12 hours after
      challenge. LPS provoked an increase in TH activity in the midbrain only, and this
      was evident for up to 24 hours after LPS administration. Thus in addition to
      previous studies demonstrating that LPS increases in vivo NA, DA and 5-HT
      release, this study shows that LPS increases the activity of the rate-limiting
      enzymes responsible for their synthesis.

PMID- 11458993
TI  - The effects of physostigmine and cholinergic receptor ligands on novelty-induced
      neophobia.
AB  - The aim of the study was to analyse in a well-established model of neophobia the
      effects of peripheral and central (ICV) administration of a prototypical and
      easily penetrating to the brain acetylcholinesterase inhibitor (AChE-I)-
      physostigmine, hemicholinium, a selective blocker of the high affinity choline
      uptake sites, as well as muscarinic and nicotinic receptor ligands. Thus, an
      attempt was made to address the question whether anxiolytic-like effects of AChE
      I, reported in the clinic, are directly related to the anti-emotional action. The
      effects of peripherally and centrally administrated cholinergic ligands on
      novelty-induced decrease in exploratory behaviour were examined in rats. It was
      found that in a limited dose-range physostigmine and nicotine given peripherally
      or ICV selectively disinhibited rat exploration in the open field, whereas
      scopolamine stimulated animal motor activity and increased thigmotaxis. Locomotor
      effects of physostigmine and nicotine appeared at the higher doses and could be
      easily separated from their anti-neophobic action. The rat's exploratory
      behaviour tended to be attenuated by central administration of hemicholinium (a
      choline uptake blocker), and it was significantly inhibited by mecamylamine (a
      nicotinic receptor antagonist), and pirenzepine (a selective M1 receptor
      antagonist). Gallamine, a selective M2 receptor antagonist, did not influence on
      animal novelty-induced anxiety-related behaviour. It is concluded that AChE-I can
      selectively affect brain emotional processes evoked by neophobia-related stimuli.
      Probably both nicotinic and M1 cholinergic receptors mediate such an action of
      AChE-I.

PMID- 11458994
TI  - Subchronic treatment with prazosin improves passive avoidance learning in aged
      mice: possible relationships to alpha1-receptor up-regulation.
AB  - While many evidences indicate that deficits of central noradrenergic
      neurotransmission are involved in the age-related decline of cognitive functions
      in animals and man, very little is known about the specific role of central
      alpha1-adrenergic receptors. Therefore, this problem was specifically addressed
      in the present communication using the alpha1-adrenoceptor antagonist prazosin as
      pharmacological tool. While the acute administration of prazosin did not affect
      passive avoidance learning of young or aged mice, an improvement of learning
      capabilities was seen after subchronic treatment, but for the aged animals only.
      An U-shaped dose response curve was seen. 0.3 mg/kg prazosin was most effective.
      Very interestingly, only for this dose a significant up-regulation of the density
      of alpha1-adrenoceptors in the mouse brain was found in the aged animals only.
      The data suggest a possible causal relationship between effects of prazosin on
      passive avoidance learning and central alpha1-receptor density.

PMID- 11458995
TI  - Magnetic resonance imaging distinguishes progressive supranuclear palsy from
      multiple system atrophy.
AB  - To establish diagnostic magnetic resonance imaging (MRI) criteria for
      differentiating progressive supranuclear palsy (PSP) from multiple system atrophy
      (MSA), magnetic resonance images from eight patients with probable PSP, 30 with
      probable MSA (nine striatonigral degeneration (MSA-P) and 21 olivopontocerebellar
      atrophy (MSA-C)), and ten age-matched controls were retrospectively studied.
      Anteroposterior diameters in the midline sagittal T1-weighted image of the
      rostral (RMT) and caudal midbrain tegmentum (CMT), caudal pons and medulla were
      measured. Divergence of the red nuclei (RN) in the axial T2-weighted image was
      judged. All PSP images had a smaller RMT diameter than the lower limit of the
      normal range, showed RN divergence, and had a pontine diameter within the normal
      range. All MSA images had a CMT diameter within the normal range; no MSA images
      showed divergence of RN. Forty-four percent (4/9) of MSA-P and 76% (16/21) of MSA
      C images had a pontine diameter smaller than the lower limit of the normal range.
      On basis of the results, we propose MRI diagnostic criteria for differentiating
      PSP from MSA.

PMID- 11458996
TI  - Unaltered cytochrome oxidase, glutamate dehydrogenase and glutaminase activities
      in platelets from patients with sporadic amyotrophic lateral sclerosis--a study
      of potential pathogenetic mechanisms in neurodegenerative diseases.
AB  - Sporadic Amyotrophic Lateral Sclerosis (SALS) is a fatal neurologic disease
      characterized by degeneration of motor neurons in the spinal cord, brainstem and
      cortex. While familial cases of ALS exist, the sporadic form accounts for the
      majority of adult-onset cases. It has been hypothesized that the
      neurodegenerative mechanisms underlying SALS might arise from glutamate-mediated
      excitotoxicity and mitochondrial dysfunction. Studies on autopsied SALS spinal
      cord and brain have reported decreased cytochrome oxidase activity, decreased
      astrocytic glutamate-transporter protein, and alterations of glutamate levels and
      glutamate metabolizing enzyme activities. We conjectured that if alterations in
      glutamate metabolism and cytochrome oxidase activity occur in the SALS central
      nervous system these alterations may also be manifested in peripheral tissues
      such as platelets in living SALS patients. In this study we compared the
      activities of cytochrome oxidase, citrate synthase, glutamate dehydrogenase and
      glutaminase in platelets from SALS and control subjects. We found that there were
      no differences in any of the enzyme activities measured between the two groups.
      Our data argue against generalized ubiquitous biochemical alterations of these
      enzymes in SALS patients.

PMID- 11458997
TI  - No evidence of association between apolipoprotein E gene regulatory region
      polymorphism and Alzheimer's disease in Japanese.
AB  - The reported association between -491 A/T polymorphism in the regulatory region
      of the apolipoprotein E gene (APOE) and increased risk for Alzheimer's disease
      (AD) is controversial: Studies of different racial and ethnic populations have
      found both positive and negative associations. Examination of -491 A/T
      polymorphism in 216 patients with sporadic AD and 157 age- and gender-matched
      controls from the Japanese population revealed that, in contrast to findings for
      Caucasian populations, the -491 T allele, but not the A allele, was significantly
      more prevalent in patients with AD than in controls. This difference disappeared
      when the subjects were stratified by the gene dose of the APOE epsilon4 allele.
      Moreover, logistic regression analysis, controlling for age, sex, and the
      presence of the APOE epsilon4 allele, showed no association between the -491
      polymorphism and AD. These results suggest that -491 polymorphism does not
      independently confer susceptibility to AD, but that this polymorphism is in
      partial linkage disequilibrium with the APOE epsilon2/3/4 polymorphism.

PMID- 11458998
TI  - In-vivo measurements of regional acetylcholine esterase activity in degenerative
      dementia: comparison with blood flow and glucose metabolism.
AB  - Memory and attention are cognitive functions that depend heavily on the
      cholinergic system. Local activity of acetylcholine esterase (AChE) is an
      indicator of its integrity. Using a recently developed tracer for positron
      emission tomography (PET), C-11-labeled N-methyl-4-piperidyl-acetate (C11-MP4A),
      we measured regional AChE activity in 4 non-demented subjects, 4 patients with
      dementia of Alzheimer type (DAT) and 1 patient with senile dementia of Lewy body
      type (SDLT), and compared the findings with measurements of blood flow (CBF) and
      glucose metabolism (CMRGlc). Initial tracer extraction was closely related to
      CBF. AChE activity was reduced significantly in all brain regions in demented
      subjects, whereas reduction of CMRGlc and CBF was more limited to temporo
      parietal association areas. AChE activity in SDLT was in the lower range of
      values in DAT. Our results indicate that, compared to non-demented controls,
      there is a global reduction of cortical AChE activity in dementia. KEYWORDS:
      Dementia, cholinergic system, acetylcholine esterase, positron emission
      tomography, cerebral blood flow, cerebral glucose metabolism.

PMID- 11458999
TI  - Hyperhomocysteinemia in dementia.
AB  - Hyperhomocysteinemia is a strong risk factor for atherosclerotic vascular
      disease, and elevated serum homocysteine is correlated with vitamin B deficiency.
      In this pilot study, significantly elevated homocysteine levels were found in
      patients with Alzheimer's disease as well as in patients with vascular dementia,
      probably indicating similar pathophysiological pathways. We found significant
      correlations between low folic acid concentrations as well as high homocysteine
      concentrations and cognitive decline. Supplementation with folic acid may be an
      inexpensive way to reduce elevated homocysteine levels in demented patients.

PMID- 11459000
TI  - No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide
      (NADH) in dementia.
AB  - Reduced nicotinamide adenine dinucleotide (NADH) is advertised as an over-the
      counter product or dietary supplement to treat Alzheimer's disease. We performed
      a 3-month open-label study with oral 10 mg/day NADH with 25 patients with mild to
      moderate dementia of the Alzheimer, vascular, and fronto-temporal types in
      addition to their current cholinomimetic drug medication. In 19 patients who
      completed the study, we found no evidence for any cognitive effect as defined by
      established psychometric tests. We conclude that NADH is unlikely to achieve
      cognitive improvements in an extent reported earlier, and present theoretical
      arguments against an effectiveness of this compound in dementia disorders.

PMID- 11459001
TI  - Dopamine activates HIV in chronically infected T lymphoblasts.
AB  - HIV infection is associated with a marked vulnerability of the dopaminergic
      system. We found recently that dopaminergic substances increase brain pathology
      in the simian model of HIV infection. In the current study we used the
      chronically HIV-infected T-lymphoblasts ACH-2 to elucidate the effects of
      dopamine (DA) on HIV infection. Cells were exposed to various concentrations of
      DA for 24 hours. Flow cytometry measurements demonstrated that DA induced a
      concentration-dependent HIV activation. To study the mechanism of action of DA,
      cells were treated besides DA with glutathione, one of the main components of
      cellular defense mechanisms against oxidative stress as well as its indirect
      precursor N-acetylcysteine. Treatment with these antioxidants attenuated DA
      induced-HIV activation indicating that changes in cellular redox states might
      have been the causative factor for the observed effect. Our data suggest that HIV
      activation is tightly linked to intracellular oxidant/antioxidant levels and that
      excessive DA exposure may modulate cellular vulnerability to HIV.

PMID- 11459002
TI  - Nicotine inhibits estrogen response element binding in the rat brain.
AB  - General injection of nicotine induced an immediate and marked inhibition of
      estrogen response element (ERE) binding in the rat brain. Either mecamylamine or
      nifedipine fully antagonized the ERE binding-inhibiting effect of nicotine.

PMID- 11459003
TI  - Pharmacological manipulations of the extinction process of fear-induced
      ultrasonic vocalization in rats.
AB  - The effects of pharmacological manipulation on the extinction process of fear
      induced ultrasonic vocalizations (USVs), which are considered distress calls
      related to anxiety, were investigated. Male Wistar rats were conditioned to emit
      USVs by being given repeated electrical foot-shocks while in a chamber. After 10
      sessions of conditioning, the animals started to emit USVs upon mere exposure to
      the shock chamber without being shocked. Using these animals, the extinction
      process of the USVs was examined. With repeated exposure to the chamber without
      shocks, the USVs first increased and then gradually decreased. i.e., the
      extinction burst was observed. Daily intraperitoneal injections of a
      benzodiazepine-GABA receptor agonist diazepam (DZP; 1.0 mg/kg) or a tricyclic
      antidepressant clomipramine (CLM; 20 mg/kg) inhibited this extinction burst.
      Moreover, CLM, but not DZP, shortened the period required for extinction as
      compared with the vehicle-treated animals. Following the extinction phase, the
      emission of USVs was enhanced by the cessation of both drug treatments. These
      results suggest that CLM would be useful for reducing anxiety-related behaviors
      in the extinction process, as long as withdrawal symptoms after long-term drug
      treatments are taken into consideration.

PMID- 11459004
TI  - Concentrations of apolipoprotein C-III in healthy cows during the peripartum
      period and cows with milk fever.
AB  - Apolipoprotein (apo) C-III is a low-molecular-mass protein mainly distributed in
      the high-density lipoprotein fraction in cattle serum. We have recently shown
      that the apoC-III concentration is decreased in cows with fatty liver, ketosis,
      left displacement of the abomasum, retained placenta and milk fever. The decrease
      was most distinct in milk fever, thereby suggesting that apoC-III is particularly
      relevant to the development of milk fever and also that apoC-III is a candidate
      diagnostic marker for this disease. The purpose of the present study was to
      examine whether the apoC-III concentration in healthy cows is altered during the
      peripartum period, to assess the usefulness of apoC-III as a marker for milk
      fever. ApoC-III concentrations in 17 cows were monitored during the peripartum
      period (-48 to +12 days from parturition). Of the 17 cows, 14 were apparently
      healthy during the period. The apoC-III concentrations in the 14 healthy cows
      were unaltered during the period from -48 to -21 days, but thereafter showed
      individual variations. Compared with values during the period from -48 to -21
      days, the apoC-III concentration was increased (137%) in 5 cows during the period
      from +1 to +12 days, whereas it decreased (60.7%) in 9 cows. Three cows suffered
      from milk fever at -3 to +10 days. Decreased apoC-III concentrations in diseased
      cows (15 to 37% of controls) were more distinct than in the 9 healthy cows. The
      apoC-III concentration was correlated with lecithin:cholesterol acyltransferase
      activity in cows with milk fever, but not in healthy cows. Correlation analysis
      also indicated that apoC-III and apoB-100 concentrations were negatively
      correlated in 5 healthy cows with increased apoC-III concentrations, but
      positively in 9 healthy cows with decreased concentrations and cows with milk
      fever. Determination of the apoC-III concentration during the peripartum period
      is suggested to be helpful in diagnosing milk fever. The possible relevance of
      apoC-III and apoB-100 in the development of milk fever is also implied.

PMID- 11459005
TI  - Molecular analysis of defect healing in rat diaphyseal bone.
AB  - Spatial expression of messenger ribonucleic acid (mRNA) for osteoblastic marker
      in drill hole defect healing of adult male rats was analyzed by in situ
      hybridization. The defect was filled with hematoma 3 days after surgery,
      expressing Type I collagen mRNA. Hematoma was replaced with fibrous tissue on day
      7, and then with new trabecular bone on day 10, originated from the intra
      medullary space, respectively. mRNA for Type I collagen, parathyroid hormone 1
      receptor (PTHIR), and alkaline phosphatase (ALP) were expressed in the same cell
      population of fibrous tissue adjacent to newly-formed trabecular bone, and in
      osteoblasts lining the newly-formed trabecular bone. Hematopoietic marrow with
      osteoclasts subsequently invaded the region, also from the intra-medullary space,
      replacing all the new trabecular bone by day 21, except for a thin sub-periosteal
      layer. mRNA for Type I collagen, PTH1R and ALP was expressed on the periosteal
      surface of thin layer. Although cartilage formation was not histologically
      visible, mRNA for Type II collagen was weakly detected in the majority of
      osteoblasts lining the newly-formed trabecular bone.

PMID- 11459006
TI  - Identification of the porcine cytomegalovirus major capsid protein gene.
AB  - A major capsid protein (MCP) gene homologue of porcine cytomegalovirus (PCMV) was
      identified. Sequence analysis indicated that the PCMV MCP gene is 4,026
      nucleotides in length encoding a protein of 1,341 amino acid residues. The
      predicted molecular weight of the PCMV MCP is 151,456 Da, equivalent to those of
      other herpesvirus MCP counterparts. Phylogenetic analysis using herpesviral MCP
      gene sequences confirmed that PCMV is a betaherpesvirus with higher homology with
      human herpesvirus-6 and -7 than human and mouse cytomegaloviruses. The serum of
      pig experimentally infected with PCMV did not react with bacterially expressed
      MCP, suggesting that the PCMV MCP may not be related to the humoral immune
      response in the course of PCMV infection. Also, we established polymerase chain
      reaction (PCR) protocols using primers corresponding to MCP gene sequences for
      detection of PCMV infection. The PCR protocol would be effective for the
      diagnosis of slow-growing PCMV infection, for which traditional methods involving
      virus-isolation are not useful.

PMID- 11459007
TI  - In vitro growth of mouse ovarian preantral follicles and the capacity of their
      oocytes to develop to the blastocyst stage.
AB  - Two groups of mouse preantral follicles with diameters of 125-150 and 151-175
      microm were cultured individually for 6 days in a medium supplemented with FSH
      and fetal calf serum to determine their in vitro growth characteristics. Their
      oocyte capacity for maturation and development to the blastocyst stage following
      in vitro fertilization was also assessed. Antral formation rate at the end of
      culture was higher in the follicles of 151-175 microm (89%) than 125-150 microm
      (76%). The timing of antrum formation was different between the two follicle
      categories: most 151-175 microm follicles formed antra earlier than 125-150
      microm follicles (days 4 and 5 vs. 5 and 6). However, follicle diameters at the
      time of antrum formation were the same regardless of the initial size and the
      culture period. Maturation rates of the oocytes derived from both categories of
      in vitro grown follicles (70 and 62%) were not different from those of oocytes
      from in vivo grown follicles (74%). The in vitro derived oocytes, however, showed
      less cleavage (30 and 35%) than the in vivo derived oocytes (89%). Although the
      oocytes from both follicle categories developed to the morula stage after in
      vitro fertilization, blastocysts were only obtained from oocytes derived from the
      151-175 microm category. These results demonstrate that an individual follicle
      culture system using a medium with FSH and fetal calf serum supports in vitro
      growth of mouse preantral follicles with diameters of 151-175 microm to the
      preovulatory stage, and that their oocytes have the capability to develop to the
      blastocyst stage.

PMID- 11459008
TI  - Ontogeny of pig discrete Peyer's patches: expression of surface antigens.
AB  - Leukocyte populations present in the discrete Peyer's patches (PP) of the pig
      were characterized from birth (Day 0) to day 35 after birth by
      immunohistochemistry and image analysis. Immediately after birth, cell membrane
      expression of CD2 and CD3, major histocompatibilty complex (MHC) class 11 (both
      SLA (swine leukocyte antigen) -DQ+ and SLA-DR+), CD21, 74-22-15 and surface
      immunoglobulin (sIg) were all demonstrable. Computer assisted morphometric
      techniques were used to confirm the significant expansion of these cell
      populations from birth onwards. The distribution of the cell types was not random
      but suggested a preferential retention of cells at specific sites. This implies a
      degree of organization of immunological cells within the discrete PP, enhancing
      the potential to mount immune responses in the most efficient manner.

PMID- 11459009
TI  - Characterization of in vitro and in vivo antiviral activity of lactoferrin and
      ribavirin upon hantavirus.
AB  - Mechanisms of anti-hantaviral activities of bovine lactoferrin (LF) and ribavirin
      (Rbv) were investigated. Hantavirus focus formation at 48 hr was 15% of the
      control in cells treated with 400 microg/ml LF for 1 hr at 37 degrees C prior to
      viral infection. Post infection treatment with 100 microg/ml Rbv also inhibited
      the focus formation to 2.5% of the control. Combined LF pre- and Rbv post
      infection treatment completely inhibited focus formation. Viral glycoprotein (G2)
      and nucleocapsid protein (NP) syntheses were delayed in LF pretreated cells up to
      24 hr post infection (hpi) but became comparable to the control by 48 hpi.
      Further, LF inhibited viral shedding at 24 hpi but did not inhibit shedding after
      48 hpi. However, Rbv was able to inhibit synthesis of viral proteins, (+) and (-)
      strand RNAs also inhibited viral shedding after 24 hr. These results suggest that
      LF inhibits viral adsorption to cells, while Rbv inhibits viral RNA synthesis.
      For in vivo trials of LF and Rbv, LF pre- and Rbv post-treatment were evaluated
      in suckling mice infected with hantavirus, of which 7% survived. LF
      concentrations of 40 and 160 mg/kg administered prior to viral challenge improved
      survival rates to 15% and 70%, respectively for single administration and 85% and
      94%, respectively, for double administration. Rbv concentrations of 25 and 50
      mg/kg gave survival rates of 68% and 81%, respectively. This suggests that both
      LF and Rbv are efficacious in hantavirus infection in vivo.

PMID- 11459010
TI  - Pulmonary atherosclerosis and pulmonary arterial pressure in cholesterol-fed New
      Zealand white rabbits.
AB  - The lung produces many vasoactive substances originating from its vascular
      endothelium and plays an important part in various pathose. The present study was
      carried out to clarify pulmonary atherosclerosis and pulmonary arterial pressure,
      and to elucidate a part of the pulmonary pathosis in cholesterol-fed rabbits.
      Atherosclerosis was induced by feeding the animals a cholesterol-rich diet. When
      the rabbits were fed the cholesterol-enriched diets for 15 weeks, the grade of
      the atherosclerosis was severer than in 8W-feeding rabbits. The lesions of 8W
      feeding rabbits were mainly composed of foam cells and fibrous components,
      whereas in 15W-feeding rabbits, the aggregation of foam cells beneath the
      endothelium of the vessel was infiltrating the media and severe stenose of the
      lumen was observed. In the entire pulmonary arterial system, the severe
      obstructive vascular lesions were localized and not diffused. The pulmonary
      arterial pressures of the rabbits increased slightly with time and the mean
      pressures were 11.3+/-0.9 (control group), 11.8+/-1.0 (8W group) and 13.7+/-1.5
      mmHg (15W group) respectively. A significant difference existed in the mean
      pressure between the control group and 15W-feeding group, but there were no
      significant differences in the systolic and diastolic pressures among the three
      groups. In conclusion, we could induce pulmonary atherosclerosis in rabbits by
      feeding them a hyper-cholesterol diet but not overt pulmonary hypertension.

PMID- 11459011
TI  - Passive protection against porcine epidemic diarrhea (PED) virus in piglets by
      colostrum from immunized cows.
AB  - The effects of hyperimmune cow colostrum (HCC) on experimentally induced porcine
      epidemic diarrhea (PED) were investigated in piglets. In experiment 1, four 2-day
      old piglets fed HCC containing an antibody titer of 1:512 and another four
      piglets fed unimmune cow colostrum (UCC) were orally inoculated with 10LD50 of
      PED virus. The piglets were given colostrum three times a day at 4 hr intervals.
      Half of the piglets fed HCC showed diarrhea and recovered, and all piglets
      survived. In contrast, all piglets fed UCC developed diarrhea and three of them
      died. In experiment 2, 2-day-old piglets fed HCC containing antibody titers of
      1:512, 1:128 and 1:32, and UCC were inoculated with PED virus, and survival rates
      after challenge were 100, 75, 50 and 0 %, respectively. In experiment 3, 1-day
      old piglets fed HCC with 1:512 antibody titer or UCC were inoculated and
      necropsied at 24, 48 and 72 hr after the inoculation for pathological
      examination. Piglets fed HCC remained healthy and PED virus antigen was not
      detected in the epithelial cells of the small intestine, and the length of the
      villi in small intestine was normal. On the other hand, in piglets fed UCC,
      villous atrophy and PED virus antigen were observed in epithelial cells of the
      jejunum and ileum from 24 hr. It was concluded that oral administration of HCC to
      piglets was effective in preventing PED virus infection and reduced their
      mortality.

PMID- 11459012
TI  - Induction of immune responses to glycoprotein gD of Aujeszky's disease virus with
      DNA immunization.
AB  - In an attempt to produce a DNA vaccine to prevent Aujeszky's disease, the
      induction of immune responses against Aujeszky's disease virus (ADV) gD was
      investigated in mice. The plasmid was constructed by placing ADV gD gene
      downstream of murine cytomegalovirus immediate early promoter of expression
      vector pMYK, which was injected twice on the skin of mice by using a gene-gun.
      All mice showed neutralizing antibodies against ADV gD at 4 weeks after
      immunization. The induction of cytotoxic T lymphocytes and splenic natural killer
      cells was also observed at 6 weeks post immunization. These results indicate that
      ADV gD gene in the form of DNA vaccine may induce specific as well as non
      specific immune responses in vivo.

PMID- 11459013
TI  - TT virus infection in gibbons.
AB  - TT virus (TTV) is not only an infectious agent of worldwide distribution but has
      also been demonstrated in various non-human primates in addition to humans. In
      the present study, we subjected the sera of 67 gibbons to PCR and nucleotide
      sequencing, with subsequent phylogenetic analysis to determine the nature of the
      relationship between TTV found in humans and non-human primates. We discovered
      the virus in 9/67 (13.4%) of the gibbon sera and subjected 6 of those to direct
      sequencing. The phylogenetic tree constructed encompassed all TTV species known
      to date, revealing a close proximity between the gibbon virus and those detected
      in Thai individuals, whereas the chimpanzee strains were phylogenetically more
      remote.

PMID- 11459014
TI  - Attachment of Malassezia pachydermatis to the ear dermal cells in canine otitis
      externa.
AB  - To investigate the predominance of Malassezia pachydermatis (M. pachydermatis) as
      a causative agent of canine otitis externa, ear cerumen samples were observed for
      adhesion of M. pachydermatis to the cornified epithelial cells by light and
      electron microscopes. The yeasts appeared not to adhere to the cornified
      epithelial cells directly, but they seemed to exist in the proximity of the
      epithelial cells with an electron opaque halo-like space around them.
      Polysaccharide and lipid staining techniques were conducted to identify the
      substances existing in that space. Lipid substances, not saccharides, were
      observed around the yeasts and the cornified epithelial cells. These results
      suggested that in the canine ear canal malassezia yeast attachment to the
      cornified epithelial cells is mediated by lipids.

PMID- 11459015
TI  - The effects of vagotomy on the abomasum in calves: radiography and protein gene
      product 9.5 immunohistochemistry.
AB  - Abomasal disorders of calves with total vagotomy, operated on at 1 week old, were
      investigated with radiography and protein gene product (PGP) 9.5
      immunohistochemistry. Radiographic findings indicated abomasal atony with
      dilatation in all calves 2 weeks after vagotomy, while 4 weeks after vagotomy
      abomasal dilatation was detected in 2 calves and another 2 calves showed
      dilatation and impaction. The densities of PGP 9.5-immunoreactive nerves in the
      tunica muscularis decreased significantly in the corpus region of the greater
      curvature 2 weeks after vagotomy and in the pyloric region of the lesser
      curvature 4 weeks after vagotomy, and it was at its lowest 4 weeks after vagotomy
      in all regions examined. In conclusion, abomasal dilatation and/or impaction in
      vagotomized calves confirmed by radiography were related with a decreased
      frequency of nerves in the tunica muscularis of the abomasum.

PMID- 11459016
TI  - Acute phase response in naturally occurring coliform mastitis.
AB  - Changes in the activities of serum cytokines and in acute phase response were
      observed in dairy cows with naturally occurring coliform mastitis. Seven cows
      with severe mastitis showed systemic and mammary inflammatory response throughout
      the observation period, and 11 cows with mild mastitis recovered and were able to
      be milked within 3 days of onset of mastitis. Serum interleukin (IL)-I and tumor
      necrosis factor (TNF) activities were higher in the severe group than in the mild
      group at the first appearance of symptoms. Elevated IL-1 activity was evident in
      the severe group throughout the observation period. Serum alpha-1
      acidglycoprotein (alpha1AG) concentration began to rise with the beginning of
      mastitis in the severe group, and peaked at 9 days. Serum haptoglobin (Hp)
      concentrations peaked at 3 days, and decreased gradually after 3 days in the
      severe group. These results showed that there are dynamic changes in serum IL-1
      activity and in serum alpha1AG and Hp concentrations in cows with severe coliform
      mastitis.

PMID- 11459017
TI  - Reliable sex identification of dogs by modified PCR/RFLP analysis.
AB  - To find definitive RFLP sites for canine sex determination, DNA segments
      corresponding to parts of the canine ZFX and ZFY genes were amplified by PCR and
      were directly sequenced. According to the newly defined sequence data, the
      combination of Haelll and Cfr13I sites was found to be useful for not only
      identifying the sex of the canine DNA samples but also distinguishing them from
      the human DNA. Conveniently, these two enzymes worked simultaneously in the same
      single buffer. The double-digestion of the ZFX/ZFY PCR products with HaeIII and
      Cfr13I showed banding patterns unique to males and females in Canis familialis.
      This PCR/RFLP method was confirmed to be applicable to various breeds of dog.

PMID- 11459018
TI  - Identification of larval-stage antigens of ascaris suum recognized with immune
      sera from pigs.
AB  - Antigens were identified from the third-stage larvae (L3) and lung-stage larvae
      of Ascaris suum by two-dimensional immunoblot method with antisera obtained from
      pigs that received chemically abbreviated Ascaris suum larval infections. Forty
      seven and 13 spots were recognized as antigens from the L3 and lung-stage larvae,
      respectively. Their apparent molecular weight ranged from 20 to 101 kDa and their
      isoelectric point from 3.6 to 8.0. The present study provides a framework for
      further molecular cloning of those antigens and consequently leads to the
      development of recombinant peptide vaccines against A. suum.

PMID- 11459019
TI  - Metallothionein expression and tumor growth in the transplantable pregnancy
      independent mouse mammary tumor.
AB  - In various human tumors, a metal binding protein, metallothionein (MT) is
      reported to play an important role in carcinogenesis. In the present preliminary
      study, MT expression and tumor growth were investigated in transplantable
      pregnancy-independent mammary tumors (TPIMT) derived from pregnancy-independent
      mammary tumors (PIMT) in GR/A mice, in order to study the possible role of MT in
      mammary carcinogenesis. TPIMT as well as PIMT showed MT expression in tumor cells
      in all of the successive transplantations. A negative correlation was observed
      between MT expression in transplanted tumor tissues and their growth in the hosts
      (r=-0.53, p<0.05). The present study indicates that MT is a useful marker of
      tumor progression in TPIMT.

PMID- 11459020
TI  - Detection of mycoplasma in mastitic milk by PCR analysis and culture method.
AB  - Mycoplasma alkalescens, M. bovigenitalium, M. bovirhinis and M. bovis were
      directly detected from milk specimens by a polymerase chain reaction (PCR) when
      milk specimens were centrifuged and treated with mycoplasmal lysis buffer. The
      sensitivity of this PCR method was 110 to 1,400 colony forming units (CFU). This
      method was useful for the detection of mycoplasmas in milk specimens from cows at
      an early stage of mycoplasmal mastitis since a small amount of mycoplasma could
      be detect in milk without culture. The results were available within 12 hr, which
      is faster than conventional culture techniques. M. bovirhinis was detected in
      more than 70% of mastitic milk specimens when mycoplasmas were detected in milk
      specimens from 30 cows with mastitis by this PCR method.

PMID- 11459021
TI  - Changes in activities of enzymes related to malate-aspartate shuttle in
      leukocytes from dogs given a herb supplement.
AB  - Changes in activities of enzymes related to the malate-aspartate shuttle were
      measured in leukocytes (WBC) from dogs given food supplemented with 2 mg/kg of
      herb powder, Echevaria glauca, every day for 4 weeks. There were no significant
      differences in plasma concentrations of glucose, immunoreactive insulin, free
      fatty acids and triglyceride between dogs given food with or without the herb
      supplementation. Activities of malate dehydrogenase (MDH) and aspartate
      aminotransferase (AST) in the malate-aspartate shuttle increased remarkably in
      mitochondria of WBC from dogs fed the herb supplementation. It is suggested that
      Echevaria glauca herb supplementation might activate NADH shuttle systems and
      mitochondrial energy metabolism in dogs.

PMID- 11459022
TI  - Marble spleen disease in pheasants in Korea.
AB  - Two pheasants maintained in outdoor closed pen died within several days after
      having a history of depression. On necropsy, the spleens from both pheasants were
      enlarged about 3 times of their normal size and appeared mottled in color varying
      white to red. Histopathologically, there were diffuse severe follicular necrosis
      in the spleen and congestion and edema in the lung. Intranuclear basophilic
      inclusion bodies, which are strongly positive to group II avian adenovirus with
      immunohistochemistry, were noted in the spleen.

PMID- 11459023
TI  - Towards new standards in university-industry collaboration.

PMID- 11459024
TI  - An appropriate apology.

PMID- 11459025
TI  - Labs seek share of NIH spending.

PMID- 11459026
TI  - Fears rise over BSE infection in UK abattoirs.

PMID- 11459027
TI  - The history man.

PMID- 11459028
TI  - Seismic sleuths.

PMID- 11459029
TI  - Smart-card traffic system keeps Singapore in the fast lane.

PMID- 11459030
TI  - Mathematical model could clarify arms race.

PMID- 11459032
TI  - A new approach to global book distribution.

PMID- 11459031
TI  - More light shed on the Mauna Kea controversy.

PMID- 11459033
TI  - Improving taxonomy for us and the other fishes.

PMID- 11459034
TI  - Bad words.

PMID- 11459036
TI  - Electronics in a spin.

PMID- 11459035
TI  - A watery arms race.

PMID- 11459037
TI  - Plant microbiology. Quieting the raucous crowd.

PMID- 11459038
TI  - Carbon cycle. The roots of the matter.

PMID- 11459039
TI  - Homing in on ant navigation.

PMID- 11459040
TI  - Crystals, asymmetry and life.

PMID- 11459041
TI  - Palaeontology. Australia's last giants.

PMID- 11459042
TI  - Neurodegenerative diseases. Origins of instability.

PMID- 11459043
TI  - The ins and outs of signalling.

PMID- 11459044
TI  - Knot tied around an octahedral metal centre.

PMID- 11459045
TI  - p25 protein in neurodegeneration.

PMID- 11459046
TI  - Reef corals bleach to survive change.

PMID- 11459047
TI  - African elephants and contraception.

PMID- 11459048
TI  - The four final rotation states of Venus.
AB  - Venus rotates very slowly on its axis in a retrograde direction, opposite to that
      of most other bodies in the Solar System. To explain this peculiar observation,
      it has been generally believed that in the past its rotational axis was itself
      rotated to 180 degrees as a result of core-mantle friction inside the planet,
      together with atmospheric tides. But such a change has to assume a high initial
      obliquity (the angle between the planet's equator and the plane of the orbital
      motion). Chaotic evolution, however, allows the spin axis to flip for a large set
      of initial conditions. Here we show that independent of uncertainties in the
      models, terrestrial planets with dense atmosphere like Venus can evolve into one
      of only four possible rotation states. Moreover, we find that most initial
      conditions will drive the planet towards the configuration at present seen at
      Venus, albeit through two very different evolutionary paths. The first is the
      generally accepted view whereby the spin axis flips direction. But we have also
      found that it is possible for Venus to begin with prograde rotation (the same
      direction as the other planets) yet then develop retrograde rotation while the
      obliquity goes towards zero: a rotation of the spin axis is not necessary in this
      case.

PMID- 11459049
TI  - Persistent sourcing of coherent spins for multifunctional semiconductor
      spintronics.
AB  - Recent studies of n-type semiconductors have demonstrated spin-coherent transport
      over macroscopic distances, with spin-coherence times exceeding 100 ns; such
      materials are therefore potentially useful building blocks for spin-polarized
      electronics ('spintronics'). Spin injection into a semiconductor (a necessary
      step for spin electronics) has proved difficult; the only successful approach
      involves classical injection of spins from magnetic semiconductors. Other work
      has shown that optical excitation can provide a short (<500 ps) non-equilibrium
      burst of coherent spin transfer across a GaAs/ZnSe interface, but less than 10%
      of the total spin crosses into the ZnSe layer, leaving long-lived spins trapped
      in the GaAs layer (ref. 9). Here we report a 'persistent' spin-conduction mode in
      biased semiconductor heterostructures, in which the sourcing of coherent spin
      transfer lasts at least 1-2 orders of magnitude longer than in unbiased
      structures. We use time-resolved Kerr spectroscopy to distinguish several
      parallel channels of interlayer spin-coherent injection. The relative increase in
      spin-coherent injection is up to 500% in the biased structures, and up to 4,000%
      when p-n junctions are used to impose a built-in bias. These experiments reveal
      promising opportunities for multifunctional spin electronic devices (such as spin
      transistors that combine memory and logic functions), in which the amplitude and
      phase of the net spin current are controlled by either electrical or magnetic
      fields.

PMID- 11459050
TI  - Jamming phase diagram for attractive particles.
AB  - A wide variety of systems, including granular media, colloidal suspensions and
      molecular systems, exhibit non-equilibrium transitions from a fluid-like to a
      solid-like state, characterized solely by the sudden arrest of their dynamics.
      Crowding or jamming of the constituent particles traps them kinetically,
      precluding further exploration of the phase space. The disordered fluid-like
      structure remains essentially unchanged at the transition. The jammed solid can
      be refluidized by thermalization, through temperature or vibration, or by an
      applied stress. The generality of the jamming transition led to the proposal of a
      unifying description, based on a jamming phase diagram. It was further postulated
      that attractive interactions might have the same effect in jamming the system as
      a confining pressure, and thus could be incorporated into the generalized
      description. Here we study experimentally the fluid-to-solid transition of weakly
      attractive colloidal particles, which undergo markedly similar gelation behaviour
      with increasing concentration and decreasing thermalization or stress. Our
      results support the concept of a jamming phase diagram for attractive colloidal
      particles, providing a unifying link between the glass transition, gelation and
      aggregation.

PMID- 11459051
TI  - Formation of chiral morphologies through selective binding of amino acids to
      calcite surface steps.
AB  - Many living organisms contain biominerals and composites with finely tuned
      properties, reflecting a remarkable level of control over the nucleation, growth
      and shape of the constituent crystals. Peptides and proteins play an important
      role in achieving this control. But the general view that organic molecules
      affect mineralization through stereochemical recognition, where geometrical and
      chemical constraints dictate their binding to a mineral, seems difficult to
      reconcile with a mechanistic understanding, where crystallization is controlled
      by thermodynamic and kinetic factors. Indeed, traditional crystal growth models
      emphasize the inhibiting effect of so-called 'modifiers' on surface-step growth,
      rather than stereochemical matching to newly expressed crystal facets. Here we
      report in situ atomic force microscope observations and molecular modelling
      studies of calcite growth in the presence of chiral amino acids that reconcile
      these two seemingly divergent views. We find that enantiomer-specific binding of
      the amino acids to those surface-step edges that offer the best geometric and
      chemical fit changes the step-edge free energies, which in turn results in
      macroscopic crystal shape modifications. Our results emphasize that the mechanism
      underlying crystal modification through organic molecules is best understood by
      considering both stereochemical recognition and the effects of binding on the
      interfacial energies of the growing crystal.

PMID- 11459052
TI  - Evidence for fault weakness and fluid flow within an active low-angle normal
      fault.
AB  - Determining the composition and physical properties of shallow-dipping, active
      normal faults (dips < 35 degrees with respect to the horizontal) is important for
      understanding how such faults slip under low resolved shear stress and
      accommodate significant extension of the crust and lithosphere. Seismic
      reflection images and earthquake source parameters show that a magnitude 6.2
      earthquake occurred at about 5 km depth on or close to a normal fault with a dip
      of 25-30 degrees located ahead of a propagating spreading centre in the Woodlark
      basin. Here we present results from a genetic algorithm inversion of seismic
      reflection data, which shows that the fault at 4-5 km depth contains a 33-m-thick
      layer with seismic velocities of about 4.3 km s(-1), which we interpret to be
      composed of serpentinite fault gouge. Isolated zones exhibit velocities as low as
      approximately 1.7 km s(-1) with high porosities, which we suggest are maintained
      by high fluid pressures. We propose that hydrothermal fluid flow, possibly driven
      by a deep magmatic heat source, and high extensional stresses ahead of the ridge
      tip have created conditions for fault weakness and strain localization on the low
      angle normal fault.

PMID- 11459053
TI  - Anisotropy of thermal diffusivity in the upper mantle.
AB  - Heat transfer in the mantle is a key process controlling the Earth's dynamics.
      Upper-mantle mineral phases, especially olivine, have been shown to display
      highly anisotropic thermal diffusivity at ambient conditions, and seismic
      anisotropy data show that preferred orientations of olivine induced by
      deformation are coherent at large scales (>50 km) in the upper mantle. Thus heat
      transport in the upper mantle should be anisotropic. But the thermal anisotropy
      of mantle minerals at high temperature and its relationship with deformation have
      not been well constrained. Here we present petrophysical modelling and laboratory
      measurements of thermal diffusivity in deformed mantle rocks between temperatures
      of 290 and 1,250 K that demonstrate that deformation may induce a significant
      anisotropy of thermal diffusivity in the uppermost mantle. We found that heat
      transport parallel to the flow direction is up to 30 per cent faster than that
      normal to the flow plane. Such a strain-induced thermal anisotropy implies that
      the upper-mantle temperature distribution, rheology and, consequently, its
      dynamics, will depend on deformation history. In oceans, resistive drag flow
      would result in lower vertical diffusivities in both the lithosphere and
      asthenosphere and hence in less effective heat transfer from the convective
      mantle. In continents, olivine orientations frozen in the lithosphere may induce
      anisotropic heating above mantle plumes, favouring the reactivation of pre
      existing structures.

PMID- 11459054
TI  - Proteorhodopsin phototrophy in the ocean.
AB  - Proteorhodopsin, a retinal-containing integral membrane protein that functions as
      a light-driven proton pump, was discovered in the genome of an uncultivated
      marine bacterium; however, the prevalence, expression and genetic variability of
      this protein in native marine microbial populations remain unknown. Here we
      report that photoactive proteorhodopsin is present in oceanic surface waters. We
      also provide evidence of an extensive family of globally distributed
      proteorhodopsin variants. The protein pigments comprising this rhodopsin family
      seem to be spectrally tuned to different habitats--absorbing light at different
      wavelengths in accordance with light available in the environment. Together, our
      data suggest that proteorhodopsin-based phototrophy is a globally significant
      oceanic microbial process.

PMID- 11459055
TI  - Large-scale forest girdling shows that current photosynthesis drives soil
      respiration.
AB  - The respiratory activities of plant roots, of their mycorrhizal fungi and of the
      free-living microbial heterotrophs (decomposers) in soils are significant
      components of the global carbon balance, but their relative contributions remain
      uncertain. To separate mycorrhizal root respiration from heterotrophic
      respiration in aboreal pine forest, we conducted a large-scale tree-girdling
      experiment, comprising 9 plots each containing about 120 trees. Tree-girdling
      involves stripping the stem bark to the depth of the current xylem at breast
      height terminating the supply of current photosynthates to roots and their
      mycorrhizal fungi without physically disturbing the delicate root-microbe-soil
      system. Here we report that girdling reduced soil respiration within 1-2 months
      by about 54% relative to respiration on ungirdled control plots, and that
      decreases of up to 37% were detected within 5 days. These values clearly show
      that the flux of current assimilates to roots is a key driver of soil
      respiration; they are conservative estimates of root respiration, however,
      because girdling increased the use of starch reserves in the roots. Our results
      indicate that models of soil respiration should incorporate measures of
      photosynthesis and of seasonal patterns of photosynthate allocation to roots.

PMID- 11459056
TI  - Proximity signal and shade avoidance differences between early and late
      successional trees.
AB  - Competitive interactions between plants determine the success of individuals and
      species. In developing forests, competition for light is the predominant factor.
      Shade tolerators acclimate photosynthetically to low light and are capable of
      long-term survival under the shade cast by others, whereas shade avoiders rapidly
      dominate gaps but are overtaken in due course by shade-tolerant, later
      successional species. Shade avoidance results from the phytochrome-mediated
      perception of far-red radiation (700-800 nm) scattered from the leaves of
      neighbours, provides early warning of shading, and induces developmental
      responses that, when successful, result in the overgrowth of those neighbours.
      Shade tolerators cast a deep shade, whereas less-tolerant species cast light
      shade, and saplings tend to have high survivorship in shade cast by conspecific
      adults, but high rates of mortality when shaded by more-tolerant species. Here we
      report a parallel relationship in which the shade-avoidance responses of three
      tree species are inversely proportional to proximity signals generated by those
      species. On this basis, early successional species generate small proximity
      signals but react strongly to them, whereas late successional species react
      weakly but generate strong signals.

PMID- 11459057
TI  - Ant odometry in the third dimension.
AB  - Desert ants (Cataglyphis) are renowned for their ability to perform large-scale
      foraging excursions and then return to the nest by path integration. They do so
      by integrating courses steered and the distances travelled into a continually
      updated home vector. Whereas the angular orientation is based on skylight cues,
      how the ants gauge the distances travelled has remained largely unclear.
      Furthermore, almost all studies on path integration in Cataglyphis, as well as in
      spiders, rodents, and humans, have aimed at understanding how the animals compute
      homebound courses in the horizontal plane. Here, we investigate for the first
      time how an animal's odometer operates when a path integration task has to be
      accomplished that includes a vertical component. We trained Cataglyphis ants
      within arrays of uphill and downhill channels, and later tested them on flat
      terrain, or vice versa. In all these cases, the ants indicated homing distances
      that corresponded not to the distances actually travelled but to the ground
      distances; that is, to the sum of the horizontal projections of the uphill and
      downhill segments of the ants' paths.

PMID- 11459058
TI  - Motion-induced blindness in normal observers.
AB  - Cases in which salient visual stimuli do not register consciously are known to
      occur in special conditions, such as the presentation of dissimilar stimuli to
      the two eyes or when images are stabilized on the retina. Here, we report a
      striking phenomenon of 'visual disappearance' observed with normal-sighted
      observers under natural conditions. When a global moving pattern is superimposed
      on high-contrast stationary or slowly moving stimuli, the latter disappear and
      reappear alternately for periods of several seconds. We show that this motion
      induced blindness (MIB) phenomenon is unlikely to reflect retinal suppression,
      sensory masking or adaptation. The phenomenology observed includes perceptual
      grouping effects, object rivalry and visual field anisotropy. This is very
      similar to that found in other types of visual disappearance, as well as in
      clinical cases of attention deficits, in which partial invisibility might occur
      despite the primary visual areas being intact. Disappearance might reflect a
      disruption of attentional processing, which shifts the system into a winner-takes
      all mode, uncovering the dynamics of competition between object representations
      within the human visual system.

PMID- 11459059
TI  - Interaction with the NMDA receptor locks CaMKII in an active conformation.
AB  - Calcium- and calmodulin-dependent protein kinase II (CaMKII) and glutamate
      receptors are integrally involved in forms of synaptic plasticity that may
      underlie learning and memory. In the simplest model for long-term potentiation,
      CaMKII is activated by Ca2+ influx through NMDA (N-methyl-D-aspartate) receptors
      and then potentiates synaptic efficacy by inducing synaptic insertion and
      increased single-channel conductance of AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid) receptors. Here we show that regulated CaMKII
      interaction with two sites on the NMDA receptor subunit NR2B provides a mechanism
      for the glutamate-induced translocation of the kinase to the synapse in
      hippocampal neurons. This interaction can lead to additional forms of
      potentiation by: facilitated CaMKII response to synaptic Ca2+; suppression of
      inhibitory autophosphorylation of CaMKII; and, most notably, direct generation of
      sustained Ca2+/calmodulin (CaM)-independent (autonomous) kinase activity by a
      mechanism that is independent of the phosphorylation state. Furthermore, the
      interaction leads to trapping of CaM that may reduce down-regulation of NMDA
      receptor activity. CaMKII-NR2B interaction may be prototypical for direct
      activation of a kinase by its targeting protein.

PMID- 11459060
TI  - Molecular mechanism of cAMP modulation of HCN pacemaker channels.
AB  - Hyperpolarization-activated cation channels of the HCN gene family contribute to
      spontaneous rhythmic activity in both heart and brain. All four family members
      contain both a core transmembrane segment domain, homologous to the S1-S6 regions
      of voltage-gated K+ channels, and a carboxy-terminal 120 amino-acid cyclic
      nucleotide-binding domain (CNBD) motif. Homologous CNBDs are responsible for the
      direct activation of cyclic nucleotide-gated channels and for modulation of the
      HERG voltage-gated K+ channel--important for visual and olfactory signalling and
      for cardiac repolarization, respectively. The direct binding of cyclic AMP to the
      cytoplasmic site on HCN channels permits the channels to open more rapidly and
      completely after repolarization of the action potential, thereby accelerating
      rhythmogenesis. However, the mechanism by which cAMP binding modulates HCN
      channel gating and the basis for functional differences between HCN isoforms
      remain unknown. Here we demonstrate by constructing truncation mutants that the
      CNBD inhibits activation of the core transmembrane domain. cAMP binding relieves
      this inhibition. Differences in activation gating and extent of cAMP modulation
      between the HCN1 and HCN2 isoforms result largely from differences in the
      efficacy of CNBD inhibition.

PMID- 11459061
TI  - Sensitive detection of pathological prion protein by cyclic amplification of
      protein misfolding.
AB  - Prions are the infectious agents responsible for transmissible spongiform
      encephalopathies. The principal component of prions is the glycoprotein PrP(Sc),
      which is a conformationally modified isoform of a normal cell-surface protein
      called PrP(C) (ref. 1). During the time between infection and the appearance of
      the clinical symptoms, minute amounts of PrP(Sc) replicate by conversion of host
      PrP(C), generating large amounts of PrP(Sc) aggregates in the brains of diseased
      individuals. We aimed to reproduce this event in vitro. Here we report a
      procedure involving cyclic amplification of protein misfolding that allows a
      rapid conversion of large excess PrP(C) into a protease-resistant, PrP(Sc)-like
      form in the presence of minute quantities of PrP(Sc) template. In this procedure,
      conceptually analogous to polymerase chain reaction cycling, aggregates formed
      when PrP(Sc) is incubated with PrP(C) are disrupted by sonication to generate
      multiple smaller units for the continued formation of new PrP(Sc). After cyclic
      amplification more than 97% of the protease-resistant PrP present in the sample
      corresponds to newly converted protein. The method could be applied to diagnose
      the presence of currently undetectable prion infectious agent in tissues and
      biological fluids, and may provide a unique opportunity to determine whether
      PrP(Sc) replication results in the generation of infectivity in vitro.

PMID- 11459062
TI  - Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine
      lactonase.
AB  - Bacterial cells sense their population density through a sophisticated cell-cell
      communication system and trigger expression of particular genes when the density
      reaches a threshold. This type of gene regulation, which controls diverse
      biological functions including virulence, is known as quorum sensing. Quorum
      sensing signals, such as acyl-homoserine lactones (AHLs), are the essential
      components of the communication system. AHLs regulate virulence gene expression
      in a range of plant and animal (including human) bacterial pathogens. AHL
      producing tobacco restored the pathogenicity of an AHL-negative mutant of Erwinia
      carotovora. Different bacterial species may produce different AHLs, which vary in
      the length and substitution of the acyl chain but contain the same homoserine
      lactone moiety. Here we show that the acyl-homoserine lactonase (AHL-lactonase),
      a new enzyme from Bacillus sp., inactivates AHL activity by hydrolysing the
      lactone bond of AHLs. Plants expressing AHL-lactonase quenched pathogen quorum
      sensing signalling and showed significantly enhanced resistance to E. carotovora
      infection. Our results highlight a promising potential to use quorum-sensing
      signals as molecular targets for disease control, thereby broadening current
      approaches for prevention of bacterial infections.

PMID- 11459063
TI  - Production of multiple plant hormones from a single polyprotein precursor.
AB  - Some animal and yeast hormone genes produce prohormone polypeptides that are
      proteolytically processed to produce multiple copies of hormones with the same or
      different functions. In plants, four polypeptides have been identified that can
      be classed as hormones (intercellular chemical messengers) but none are known to
      be produced as multiple copies from a single precursor. Here we describe a
      polyprotein hormone precursor, present in tobacco plants, that gives rise to two
      polypeptide hormones, as often found in animals and yeast. The tobacco
      polypeptides activate the synthesis of defensive proteinase-inhibitor proteins in
      a manner similar to that of systemin, an 18-amino-acid polypeptide found in
      tomato plants. The two tobacco polypeptides are derived from each end of a 165
      amino-acid precursor that bears no homology to tomato prosystemin. The data show
      that structurally diverse polypeptide hormones in different plant species can
      serve similar signalling roles, a condition not found in animals or yeast.

PMID- 11459064
TI  - Structure of a human gammadelta T-cell antigen receptor.
AB  - T-cell antigen receptors composed of gamma and delta polypeptide chains
      (gammadelta TCRs) can directly recognize antigens in the form of intact proteins
      or non-peptide compounds, unlike alphabeta TCRs, which recognize antigens bound
      to major histocompatibility complex molecules (MHC). About 5% of peripheral blood
      T cells bear gammadelta TCRs, most of which recognize non-peptide phosphorylated
      antigens. Here we describe the 3.1 A resolution structure of a human gammadelta
      TCR from a T-cell clone that is phosphoantigen-reactive. The orientation of the
      variable (V) and constant (C) regions of the gammadelta TCR is unique when
      compared with alphabeta TCRs or antibodies, and results from an unusually small
      angle between the Vgamma and Cgamma domains. The complementarity-determining
      regions (CDRs) of the V domains exhibit a chemically reasonable binding site for
      phosphorylated antigens, providing a possible explanation for the canonical usage
      of the Vgamma9 and Vdelta2 gene segments by phosphoantigen-reactive receptors.
      Although the gammadelta TCR V domains are similar in overall structure to those
      of alphabeta TCRs, gammadelta TCR C domains are markedly different. Structural
      differences in Cgamma and Cdelta, and in the location of the disulphide bond
      between them, may enable gammadelta TCRs to form different recognition/signalling
      complexes than alphabeta TCRs.

PMID- 11459065
TI  - Plant pathogens and integrated defence responses to infection.
AB  - Plants cannot move to escape environmental challenges. Biotic stresses result
      from a battery of potential pathogens: fungi, bacteria, nematodes and insects
      intercept the photosynthate produced by plants, and viruses use replication
      machinery at the host's expense. Plants, in turn, have evolved sophisticated
      mechanisms to perceive such attacks, and to translate that perception into an
      adaptive response. Here, we review the current knowledge of recognition-dependent
      disease resistance in plants. We include a few crucial concepts to compare and
      contrast plant innate immunity with that more commonly associated with animals.
      There are appreciable differences, but also surprising parallels.

PMID- 11459066
TI  - Gene silencing as an adaptive defence against viruses.
AB  - Gene silencing was perceived initially as an unpredictable and inconvenient side
      effect of introducing transgenes into plants. It now seems that it is the
      consequence of accidentally triggering the plant's adaptive defence mechanism
      against viruses and transposable elements. This recently discovered mechanism,
      although mechanistically different, has a number of parallels with the immune
      system of mammals.

PMID- 11459067
TI  - Natural products and plant disease resistance.
AB  - Plants elaborate a vast array of natural products, many of which have evolved to
      confer selective advantage against microbial attack. Recent advances in molecular
      technology, aided by the enormous power of large-scale genomics initiatives, are
      leading to a more complete understanding of the enzymatic machinery that
      underlies the often complex pathways of plant natural product biosynthesis.
      Meanwhile, genetic and reverse genetic approaches are providing evidence for the
      importance of natural products in host defence. Metabolic engineering of natural
      product pathways is now a feasible strategy for enhancement of plant disease
      resistance.

PMID- 11459068
TI  - Programmed cell death, mitochondria and the plant hypersensitive response.
AB  - The plant response to attempted infection by microbial pathogens is often
      accompanied by rapid cell death in and around the initial infection site, a
      reaction known as the hypersensitive response. This response is associated with
      restricted pathogen growth and represents a form of programmed cell death (PCD).
      Recent pharmacological and molecular studies have provided functional evidence
      for the conservation of some of the basic regulatory mechanisms underlying the
      response to pathogens and the activation of PCD in animal and plant systems. In
      animals, the mitochondrion integrates diverse cellular stress signals and
      initiates the death execution pathway, and studies indicate a similar involvement
      for mitochondria in regulating PCD in plants. But many of the cell-death
      regulators that have been characterized in humans, worms and flies are absent
      from the Arabidopsis genome, indicating that plants probably use other regulators
      to control this process.

PMID- 11459069
TI  - Surface-to-air signals.
AB  - Powerful volatile regulators of gene expression, pheromones and other airborne
      signals are of great interest in biology. Plants are masters of volatile
      production and release, not just from flowers and fruits, but also from
      vegetative tissues. The controlled release of bouquets of volatiles from leaves
      during attack by herbivores helps plants to deter herbivores or attract their
      predators, but volatiles have other roles in development and in the control of
      defence gene expression. Some of these roles may include long-distance signalling
      within and perhaps between plants.

PMID- 11459070
TI  - Co-evolution and plant resistance to natural enemies.
AB  - Co-evolution between plants and their natural enemies is generally believed to
      have generated much of the Earth's biological diversity. A process analogous to
      co-evolution occurs in agricultural systems, in which natural enemies adapt to
      crop resistance introduced by breeding or genetic engineering. Because of this
      similarity, the investigation of resistance mechanisms in crops is helping to
      elucidate the workings of co-evolution in nature, while evolutionary principles,
      including those derived from investigation of co-evolution in nature, are being
      applied in the management of resistance in genetically engineered crops.

PMID- 11459071
TI  - Engineering disease resistance in plants.
AB  - Ever since the initial discovery of the molecules and genes involved in disease
      resistance in plants, attempts have been made to engineer durable disease
      resistance in economically important crop plants. Unfortunately, many of these
      attempts have failed, owing to the complexity of disease-resistance signalling
      and the sheer diversity of infection mechanisms that different pathogens use.
      Although disease-resistant transgenic plants or seeds are not yet available
      commercially, future product development seems likely as our current level of
      understanding of pathogenesis and plant defence improves.

PMID- 11459072
TI  - Effect of light on 5-methoxyindole-3-acetic acid in the rat.
AB  - This study aims to determine the effects of light on the levels of 5-MIAA to
      provide further information on this indoleamine, using a sensitive and specific
      radioimmunoassay (RIA) for immunoreactive 5-methoxyindole-3-acetic acid (5-MIAA)
      developed in our laboratories using a specific antibody and tritiated label.
      Significant differences were found in the immunoreactive 5-MIAA levels between
      mid-light and mid-dark pineal glands in rats adapted to 12/12 hrs light/dark and
      in constant darkness. Under constant light, the circadian rhythm was abolished.
      The rat serum displayed no diurnal variations in 5-MIAA levels under aux photic
      conditions. The persistence of rhythms found in constant darkness but abolished
      in constant light suggests that the pineal 5-MIAA is endogenous and uses light as
      an environmental cue. In addition to melatonin, 5-MIAA could possibly be another
      pineal photoperiodic signal in animals.

PMID- 11459073
TI  - Opposite effect of simple tetrahydroisoquinolines on amphetamine- and morphine
      stimulated locomotor activity in mice.
AB  - Endogenous tetrahydroisoquinolines, such as 1,2,3,4-tetrahydroisoquinoline (TIQ)
      and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), were
      tested for their interaction with motor effects of amphetamine and morphine in
      C57BL/6 mice. TIQ binding to cortical adrenergic alpha1, alpha2 and beta
      receptors, striatal dopamine D1 and D2 receptors and cortical L-type calcium
      channels in the Wistar rat was also studied. Both compounds in high doses reduced
      the mouse locomotor activity, and in doses not affecting activity inhibited the
      motor stimulation induced by amphetamine, 2 or 3 mg/kg i.p., but facilitated the
      hyperactivity induced by 10 mg/kg of morphine. TIQ did not displace ligands that
      are antagonists for several receptor sites (including D1 and D2 receptors), but
      displaced an agonist of alpha2-adrenoceptor, clonidine. It is proposed that TIQ
      and salsolinol specifically antagonize the agonistic conformation of dopamine
      receptor and that endogenous 1,2,3,4-tetrahydroisoquinolines may play a role of
      natural feedback regulators of the activity of dopaminergic system.

PMID- 11459074
TI  - Brain glycine levels in triazolam-treated albino rats.
AB  - The present study investigates the effects of acute and chronic administration of
      triazolam in albino rats on glycine levels in different brain areas. Three
      experiments were conducted. In the first, five groups of rats were acutely
      treated with different doses of triazolam (0.25 mg/kg-4.0 mg/kg i.p.). In the
      second experiment, rats were treated chronically by a single daily dose of
      triazolam (started by 0.25 mg/kg and increased by time to 1.0 mg/kg) for 5 weeks,
      simulating clinical use. In the third, rats were treated chronically three daily
      doses of triazolam (started by 0.25 mg/kg and increased by time to 0.5 mg/kg) for
      20 days, simulating a form of drug abuse. Brain levels of glycine and plasma
      levels of triazolam were measured using HPLC technique. The acute triazolam
      administration produced an increase in glycine levels in almost all brain areas
      studied. The chronic administration of single daily dose of triazolam produced
      normal glycine levels in most of the brain areas; this indicates the development
      of tolerance to glycine content increasing action of triazolam. The chronic
      administration of three daily doses of triazolam produced a decrease in glycine
      levels in almost all brain regions studied, which might be a prerequisite for
      oncoming withdrawal syndrome.

PMID- 11459075
TI  - Antioxidant and pro-oxidant capacity of catecholamines and related compounds.
      Effects of hydrogen peroxide on glutathione and sphingomyelinase activity in
      pheochromocytoma PC12 cells: potential relevance to age-related diseases.
AB  - The antioxidant and pro-oxidant capacity of catecholamines (CA) and related
      compounds were analyzed using the oxygen radical absorbance capacity (ORAC)
      assay. In the assay 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH), a
      peroxyl radical generator, ROO*; H2O2-Cu2+, mainly a hydroxyl radical generator,
      *OH; and Cu2+ a transition metal were used. The antioxidant effect of CA and its
      related compounds were in the order: neurotransmitters: dopamine (DA),
      norepinephrine (NE) > metabolites > amino acid precursors as measured by using
      AAPH. The antioxidant effect of CA and related compounds as measured by using
      AAPH were linearly correlated with concentration, while the antioxidant effect of
      CA in scavenging *OH produced by H2O2-Cu2+ increased proportionally to
      concentration at low concentration, but after reaching a maximum declined with
      increasing concentration. In the presence of Cu2+, CA acted as pro-oxidant.
      Glutathione (GSH) acted as a pro-oxidant when H2O2-Cu2+ or when Cu2+ alone was
      used as an oxidant and showed much higher pro-oxidant effect than DA, which could
      have relevance in the vulnerability of dopaminergic neurons to oxidative stress
      in the aging and aging related diseases. The antioxidant capacity of CA and many
      related compounds seems to be correlated with the numbers of hydroxyl groups and
      their position on the benzoic ring. The O-methylation and sulfate conjugation of
      the hydroxyl substitution inactivates both the antioxidant and pro-oxidant
      activities of CA. Our results show that oxidative stress induced by low (5
      microM) or high (300 microM) doses H2O2 in pheochromocytoma PC12 cells
      significantly up-regulate the activity of Mg-dependent neutral sphingomyelinase
      (Sase), and significantly decreased GSH.

PMID- 11459076
TI  - Benserazide decreases central AADC activity, extracellular dopamine levels and
      levodopa decarboxylation in striatum of the rat.
AB  - In Parkinsonian patients treated with levodopa, peripheral decarboxylase
      inhibitors like carbidopa and benserazide are used to increase the central
      availability of levodopa. In experimental animal studies, this clinical situation
      is mimicked. However, at the dose used in many animal studies, both benserazide
      and carbidopa pass the blood brain barrier. In this study, we investigated to
      what extent their presence in brain inhibits striatal aromatic amino acid
      decarboxylase activity. At 50 mg/kg i.p., both carbidopa and benserazide
      decreased striatal decarboxylase activity. At 10 mg/kg i.p., only benserazide
      decreased the enzyme activity, but this did not change extracellular dopamine in
      striatum and allowed dopamine levels to increase after levodopa administration.
      In contrast, the inhibition of central decarboxylase activity by 50 mg/kg
      benserazide decreased striatal dopamine levels and prevented the levodopa-induced
      increase. Therefore, it is important to carefully consider the dose of the
      peripheral decarboxylase inhibitor used when the central effects of levodopa are
      studied.

PMID- 11459077
TI  - Correlating rates of cerebral atrophy in Parkinson's disease with measures of
      cognitive decline.
AB  - We studied eight clinically non-demented PD patients and ten age-matched controls
      with serial volumetric T1-weighted MRI. All PD patients underwent full
      neuropsychological testing at baseline and follow up scans. Sub-voxel
      coregistration of the serial MRI scans with quantification of changes in total
      brain substance and ventricular size per year was performed. The PD patients had
      significant reductions in both percentage and absolute annual brain volume loss
      when compared to age-matched controls (p < 0.001). There were significant
      correlations between reductions in percentage brain volume loss and estimated
      reductions in performance IQ (r = 0.841, p = 0.004) and full scale IQ (r = 0.63,
      p = 0.049), measured by subtracting IQ measures at time of follow up scan from
      premorbid estimates. In conclusion, PD patients have a significant rate of median
      brain volume loss [10.35 (range) 6.69-16.90 ml/year] with no significant loss
      seen in age-matched controls, and these changes correlate with global measures of
      cognitive decline. Further longitudinal studies could evaluate whether serial
      volumetric MRI is a useful technique in predicting the preclinical onset of
      dementia in Parkinson's disease patients, and its role in the assessment of
      putative treatments for slowing disease progression.

PMID- 11459078
TI  - Effects of Cerebrolysin on the outgrowth and protection of processes of cultured
      brain neurons.
AB  - Cerebrolysin (Cere, EBEWE Arzneimittel, Austria), a peptidergic drug produced by
      a standardised enzymatic breakdown of porcine brain proteins, consists of a
      mixture of 75% free amino acids and 25% low molecular weight peptides (<10 k DA).
      Cerebrolysin was shown to protect against MAP2 loss in primary embryonic chick
      neuronal cultures after brief histotoxic hypoxia and in a rat model of acute
      brain ischemia. Since MAP2 is involved in processes like neuronal growth,
      plasticity and dendritic branching, we address the question whether Cere is
      protecting processes against degeneration in a chronic low serum (2% FCS) cell
      stress model and whether the spontaneous outgrowth of axon-like processes is
      influenced. This was accomplished by quantification of the neurite lengths of
      embryonic chicken telencephalon neurons after 4 and 8 days. Additionally, time
      lapse video microscopy was performed to study a possible influence of Cere on the
      growth cone behaviour of axon-like processes. To distinguish between effects
      caused by the peptide fraction and the effects related to free amino acids, we
      used an artificial amino acid solution (AA-mix). Results demonstrate a process
      outgrowth promoting effect of the AA-mix and Cere after 4 DIV. After 8 days
      neuronal network degeneration occurred in the AA-mix treated cultures, whereas
      Cere treated cultures still presented a well differentiated neuronal network.
      Dying neurons could release factors possibly impeding neurite outgrowth and Cere
      was shown to increase the viability of chicken cortical neurons. Neither the
      addition of BDNF nor serum supplementation (5% and 10% FCS) could protect the
      neuronal network against degeneration after 8 DIV, although these treatments were
      shown to ameliorate the viability of chicken telencephalon neurons. This result
      together with the finding obtained using the artificial amino acid solution
      points to the peptide fraction of Cere to be responsible for the protection of
      processes against degeneration. Time-lapse studies of Cere treated cultures
      revealed a significant decrease of the velocities characterising random growth
      cone movements, which is thought to be responsible for an increase in the length
      of axon-like processes after 4 DIV.

PMID- 11459079
TI  - Famotidine treatment of children with autistic spectrum disorders: pilot research
      using single subject research design.
AB  - Using single subject research design, we performed pilot research to evaluate the
      safety and efficacy of famotidine for the treatment of children with autistic
      spectrum disorders. We studied 9 Caucasian boys, 3.8-8.1 years old, with a DSM-IV
      diagnosis of a pervasive developmental disorder, living with their families,
      receiving no chronic medications, and without significant gastrointestinal
      symptoms. The dose of oral famotidine was 2 mg/kg/day (given in two divided
      doses); the maximum total daily dose was 100 mg. Using single-subject research
      analysis and medication given in a randomized, double-blind, placebo-controlled,
      cross-over design, 4 of 9 children randomized (44%) had evidence of behavioral
      improvement. Primary efficacy was based on data kept by primary caregivers,
      including a daily diary; daily visual analogue scales of affection, reciting, or
      aspects of social interaction; Aberrant Behavior Checklists (ABC, Aman); and
      Clinical Global Improvement scales. Children with marked stereotypy (meaningless,
      repetitive behaviors) did not respond. Our subjects did not have prominent
      gastrointestinal symptoms and endoscopy was not part of our protocol; thus, we
      cannot exclude the possibility that our subjects improved due to the effective
      treatment of asymptomatic esophagitis. The use of famotidine for the treatment of
      children with autistic spectrum disorders warrants further investigation.

PMID- 11459080
TI  - Facial nerve repair and regeneration: an overview of basic principles for
      neurosurgeons.
AB  - The facial nerve may be damaged by trauma, surgical manipulation, inflammation or
      neoplastic disease. Current techniques for repair and regeneration of the damaged
      nerve produce suboptimal results. This review outlines the current knowledge of
      experimental facial nerve regeneration in vitro and in vivo to provide an insight
      for neurosurgeons in clinical practice.

PMID- 11459081
TI  - Intra-aortic balloon counterpulsation: augmentation of cerebral blood flow after
      aneurysmal subarachnoid haemorrhage.
AB  - OBJECTIVE: To measure cerebral blood flow before and after intra-aortic balloon
      counterpulsation (IABC) in patients at high risk of developing delayed cerebral
      ischaemia after aneurysm surgery following subarachnoid haemorrhage. METHODS: Six
      prospectively selected patients at high risk of developing delayed ischaemia had
      elective IABC after clipping of their cerebral aneurysm(s). The IAB inflates in
      early diastole and deflates at the end of diastole to increase cardiac perfusion
      and decrease afterload. This results in enhanced cardiac efficiency. It also
      augments cerebral blood flow (CBF). RESULTS: We demonstrated a significant
      increase in the mean hemispheric CBF from the preoperative (preIABC) value of
      35.6 mls/100 g/min to 50.9 +/- 12.3 mls/100 g/min (p = 0.0042) as a result of
      balloon augmentation. Each patient developed a neurological deficit as a result
      of delayed cerebral ischaemia. These were reversed in 5 patients with increased
      CBF. There were minimal balloon related complications. CONCLUSION: IABC
      consistently enhanced CBF in these patients and resulted in stable cardiovascular
      parameters. This represents a possible new technique in the management of
      cerebral ischaemia following subarachnoid haemorrhage and needs further
      assessment to ascertainlits role.

PMID- 11459082
TI  - Transvenous embolization for vertebral arteriovenous fistula: report of two cases
      and technical notes.
AB  - BACKGROUND: Vertebral arteriovenous fistulas are relatively rare. Although the
      common treatment is transarterial embolization, it may be impossible to pass
      through the fistula (e.g. a microfistula created by a needle puncture). We report
      two patients with vertebral arteriovenous fistulas due to penetrating trauma who
      were successfully treated by transvenous embolization. METHOD: We present 2
      patients with vertebral arteriovenous fistulas. One patient is presented to
      demonstrate complications following attempted internal jugular cannulation and
      the other is presented to demonstrate complications after surgery for a jugular
      foramen neurinoma. Both patients manifested the sign of a severe bruit. FINDINGS:
      To identify the fistula point, simultaneous transarterial and transvenous
      angiography was performed. Using the transvenous approach, microcoils were
      applied to the fistula and the bruit completely disappeared. Interpretation.
      Transvenous embolization is a useful technique and a first-choice strategy to
      treat patients with the vertebral arteriovenous fistula due to penetrating
      trauma.

PMID- 11459083
TI  - Juxtafacet cyst of the lumbar spine. Clinical, radiological and therapeutic
      aspects in 28 cases.
AB  - OBJECT: A consecutive series of 28 "operated" juxtafacet cysts is reported. We
      emphasize the clinical and radiological aspects leading to diagnosis. We also
      discuss the results of the surgical treatment. MATERIAL AND METHODS: Medical
      information and radiological studies involving 28 patients were analyzed. Each
      patient has been operated on by decompressive laminectomy and resection of the
      cyst. The diagnosis was always confirmed by a pathological examination. The cyst
      most frequently occurred at the L4-L5 level (n = 18), and seldom at the L5-S1 (n 
      6) or L3-L4 (n - 4) levels. RESULTS: The differential diagnosis from other
      pathological causes responsible for a radicular compression could not be done by
      physical examination. Spine X-rays or myelogram were nonspecific. Computed
      Tomography or CT-myelography could help in the diagnosis but MR imaging was the
      most sensitive. In our series, the respective sensitivities of these techniques
      are 56, 42 and 77%. The preoperative diagnosis was correct in 18 patients (64%).
      The cyst was sometimes adherent to the underlying dura, then significantly
      increasing the risk of dural tear and spinal fluid leak, especially when located
      at L3-L4 level. Surgical ablation lead to a complete recovery or an important
      improvement in 26 patients. CONCLUSIONS: The diagnosis of the juxtafacet cyst of
      the lumbar spine is better achieved by MRI. Surgery is the gold standard
      treatment, safe and long-term effective. When a total cyst removal with an
      internal facetectomy are performed, recurrence is exceptional.

PMID- 11459084
TI  - Coagulopathy induced spinal intradural extramedullary haematoma: report of three
      cases and review of the literature.
AB  - In a retrospective review of patients operated for coagulopathy induced spinal
      intradural-extramedullary haematoma the literature regarding coagulopathy induced
      spinal haemorrhage is reviewed and the etiology of these rare spinal subdural and
      subarachnoid haemorrhages is discussed. Spinal intradural haematomas are usually
      related to trauma or a previous lumbar puncture. A review of the literature
      revealed only a handful cases of spinal intradural haemorrhages occurring
      secondary to an underlying haematological disorder or an iatrogenic coagulopathy.
      Coagulopathy induced spinal haemorrhage should be included in the differential
      diagnosis of acute paraparesis in patients with co-existent haematological
      disorders or undergoing anticoagulation therapy. Due to the often mixed subdural
      and subarachnoid bleeding patterns we have termed this entity spinal intradural
      extramedullary haematoma.

PMID- 11459085
TI  - A more basal approach in microvascular decompression for hemifacial spasm: the
      para-condylar fossa approach.
AB  - BACKGROUND: In view of the fact that a basal craniectomy in microvascular
      decompression (MVD) for hemifacial spasm (HFS) can minimize cerebellar retraction
      and expose the facial nerve root exit zone (FNREZ) directly from below without
      placement of tension on the seventh-eighth cranial nerve complex, we used a more
      basal approach in 32 patients with typical HFS. METHOD: A slightly curved skin
      incision 5 cm in length and 2 cm posterior and parallel to the mastoid notch was
      made. The basal lateral occipital plate including the lateral one-fourth of the
      condylar fossa and the posterior one-fourth of the jugular process were removed.
      For the early drainage of cerebrospinal fluid through a small dural hole, the
      basal occipital plate posteromedial to the condylar fossa was removed. With this
      basal craniectomy, minimum elevation of the cerebellar tonsil and flocculus could
      expose FNREZ safely. FINDINGS: Thirty one of 32 patients displayed complete
      disappearance of spasm following surgery. One patient showed 70% decrease of
      spasm. Delayed transient facial weakness occurred in one patient. Audiometries
      showed no postoperative hearing decrease in any patient, even though no intra
      operative monitoring of the cochlear function was undertaken. INTERPRETATION:
      Although this basal approach, the para-condylar fossa approach, is a slightly
      basal modification of the conventional procedure, it may minimize complications.

PMID- 11459086
TI  - Immunohistochemical localisation of cytokeratins in craniopharyngioma.
AB  - BACKGROUND: Although craniopharyngiomas have been examined in several
      microscopical studies to date, immunohistochemical analysis has not been
      sufficient. METHOD: In addition to the routine haematoxylin and eosin staining,
      38 cases of intra- and/or supra-sellar craniopharyngioma, including 34
      adamatinomatous and 4 squamous papillary types, were studied using
      immunohistochemistry for expression of four types of cytokeratin. FINDINGS:
      Histological examination found epithelial cells in 26 of 38 (68.40%) cases.
      However, cytokeratins were demonstrated in 35 of 38 (92.1%) cases. The remaining
      3 cases without demonstration of epithelial cell nests were supposed to be
      adamantinomatous craniopharyngiomas based on the findings in the stroma. In 31 of
      34 adamantinomatous craniopharyngioma cases, the epithelium was detected by
      immunostaining for cytokeratins. The epithlieum expressed 56 kDa (KL-1) and 40
      kDa (cytokeratin 19) cytokeratins with similar staining patterns and intensities.
      The staining intensity of 54 kDa cytokeratin (cytokeratin 7) was similar to that
      of the high molecular weight cytokeratin (keratin M-903). However, in many cases
      (15 of 27), immunoreactivity of cytokeratin 7 was not demonstrated in an outer
      palisaded basal layer. In all 4 squamous papillary craniopharyngiomas, moderate
      staining with cytokeratin 7 appeared in the superficial layer, whereas basal or
      mid-zone epithelial cells were negative for cytokeratin 7. The basal layer
      stained negatively for KL-1, as well as cytokeratin 7. INTERPRETATION:
      Immunostaining for cytokeratin is valuable in the investigation of
      craniopharyngioma, especially when specimens contain only a small or questionable
      part of epithelium. Most notably, KL-1 or cytokeratin 7 stainings are suitable
      for analyzing these tumours, with special reference to histological subtypes.

PMID- 11459087
TI  - Expression and significance of vascular permeability factor in tumour
      infiltrating lymphocytes of brain metastases.
AB  - BACKGROUND: Recently, vasogenic edema has been related to the expression of
      vascular permeability factor (VPF) by tumour cells in brain metastases. On the
      other hand, expression of VPF has been reported in inflammatory cells. Keeping in
      mind the current presence of tumour-infiltrating lymphocytes (TIL) in brain
      metastases, our objective is to study the expression and significance of VPF in
      TIL-cells from specimens of brain metastases. METHOD: Tumour samples from 16
      brain metastases associated with peritumoural edema were immunohistochemically
      studied for demonstration of VPF. The degree of VPF-expression by tumour cells
      and TIL was determined, and correlated with the degree of peritumoural edema.
      FINDINGS: Our present results show that, independently of the VPF-positivity
      expressed by the tumour cells, VPF-expression is a constant finding in TIL-cells
      of brain metastases, and correlated with the amount of peritumoural edema.
      INTERPRETATION: Our present findings suggest a role for TIL-cells in the
      development of vasogenic edema associated with brain metastases.

PMID- 11459088
TI  - Prognostic value of vascular endothelial growth factor and its receptors Flt-1
      and Flk-1 in astrocytic tumours.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF )/ vascular permeability
      factor (VPF) is an important regulator of angiogenesis and vascular permeability.
      METHOD: We examined immunohistochemically expressions of VEGF and its
      corresponding receptors Flt-1 and Flk-1 in a series of 50 astrocytic tumours. and
      correlated their expressions with the degree of angiogenesis, brain edema and
      prognosis. FINDINGS: There were significant relationships between VEGF, Flk-1
      expressions and glioma malignancy grading, intratumoural vascularity and
      peritumoural brain edema, respectively. Patients with VEGF positive low grade
      astrocytoma and glioblastoma multiforme had a significantly shorter mean overall
      survival time than those with negative tumours (P = 0.0010 and 0.0180,
      respectively). Flk-1 is also a sigrificant prognostic factor within each tumour
      grade, which has a negative impact on overall survival. Additionally,
      overexpression of VEGF and Flk-1 were significantly associated with earlier
      recurrence in patients with low grade astrocytomas (P = 0.0018 and 0.0240,
      respectively). INTERPRETATION: It is possible to subcategorize each grade of
      astrocytic tumours based on their VEGF and Flk-1 staining pattern, which may be
      crucial in predicting the biological behavior of tumours and thus provide useful
      information with regard to adequate treatment.

PMID- 11459089
TI  - Neurosurgery in Hungary. A historical overview and the present state.

PMID- 11459090
TI  - Needle brain necropsy through percutaneous craniostomy: technical note.

PMID- 11459091
TI  - "Vascular tunnel" formation to improve the effect of decompressive craniectomy in
      the treatment of brain swelling caused by trauma and hypoxia.

PMID- 11459092
TI  - Spinal cord stimulation and early experimental cerebral spasm: the "functional
      monitoring" and the "preventing effect".
AB  - BACKGROUND: Clinical and experimental data on cerebral blood flow (CBF) changes
      during spinal cord stimulation (SCS) were published since 1986. The aims of the
      present work are: 1. To find an experimental model of reliable, simple and in
      vivo monitoring of "early" basilar artery spasm after subarachnoid haemorrhage
      (SAH) and 2. To investigate the effects of cervical spinal cord stimulation
      (CSCS) on it. Vasospasm due to SAH is both "acute" and "recurrent". Early spasm
      occurs within minutes of the SAH. its duration is approximately 1 hour. The need
      of different morphological and haemodynamic methods to evaluate experimental
      early spasm is reported. To overcome intracranial surgical manipulations and
      biological effects of contrast and fixation media we designed a model that allows
      "in vivo" functional monitoring of basilar blood flow far away from the spasm
      without direct surgical and chemical interference. Subsequently we investigated
      the effects of CSCS on the new model of "functional monitoring" of the "early"
      cerebral vasospasm. METHOD: 29 adult Burgundy rabbits were studied. Group 1:
      under homeostatic monitoring, "on-line" carotid blood flow (carotid BF) changes
      produced by SAH in cisterna magna of 12 (plus 5 sham treated) animals were
      studied from the common carotid artery after external carotid artery occlusion
      before, during SAH and up to the end of the experiments. All the animals
      underwent digital subtraction cerebral panangiography (CPA) after SAH obtaining a
      significant increase of carotid BF only when basilar vasospasm was shown by CPA.
      Carotid BF increase during basilar vasospasm was defined "functional monitoring"
      of early spasm. Group 2: Twelve animals wearing a cervical epidural electrode
      underwent carotid BF "functional monitoring" of early basilar spasm before and
      during CSCS. FINDINGS: Carotid BF changes during CSCS occurred in 10 animals. No
      carotid BF changes (i.e. no basilar vasospasm) occurred after SAH up to the end
      of the experiments in all the stimulated animals. INTERPRETATION: CSCS is able to
      prevent "early spasm" due to SAH in all the animals studied with the new model of
      "functional monitoring" described, independently from the occurence and the sign
      for stimulation-induced carotid BF variations. The role and the limits of
      reversible functional sympathectomy in mediating the effect of CSCS on early
      vasospam are discussed.

PMID- 11459093
TI  - Newly developed aneurysm increased and ruptured 1 month after clipping of first
      aneurysm where the parent artery was abnormal.

PMID- 11459094
TI  - The strange association of pneumosinus dilatans and arachnoid cyst: case report
      and review of the literature.
AB  - BACKGROUND: The authors present the case of a 71-year-old man with dramatic
      pneumosinus dilatans adjacent to a large, symptomatic, fronto-temporal arachnoid
      cyst. METHOD: The literature on pneumosinus dilatans and its association with
      arachnoid cyst is reviewed. FINDINGS: Pneumosinus dilatans may be either
      idiopathic, a reaction to an adjacent meningioma, or an 'ex-vacuo' response to
      cerebral volume loss and intracranial hypotension. It is also found with large
      arachnoid cysts and is probably under-recognised in this context. The co
      existence of an expansile intradural lesion with changes in the skull base that
      tend to reduce the intracranial volume is puzzling, and has not yet been fully
      explained. Differences in the relative timing of paranasal sinus and arachnoid
      cyst growth, and the 'temporal agenesis' theory of arachnoid cyst formation have
      been proposed but do not account for all the features of this unusual
      association. INTERPRETATION: Pneumosinus dilatans is a useful and under
      recognised indicator of the presence and chronicity of a variety of intracranial
      pathologies. Its association with arachnoid cyst is paradoxical, and a new
      explanation is offered as to how this may arise.

PMID- 11459095
TI  - Pure V1 trigeminal neuralgia caused by a cryptic trigeminal neurinoma.
AB  - Most idiopathic trigeminal neuralgias are caused by vascular compression at the
      root entry zone of the trigeminal nerve. (Dandy [1] and Jannetta [2]) We report a
      case of pure V1 trigeminal neuralgia caused by a small trigeminal neurinoma which
      had not been detected on preoperative neuroradiological examination.

PMID- 11459096
TI  - Pineal epidermoid cyst visualized by diffusion-weighted magnetic resonance
      imaging.

PMID- 11459097
TI  - A single- and a dual-fractal analysis of antigen-antibody binding kinetics for
      different biosensor applications.
AB  - The diffusion-limited binding kinetics of antigen (or antibody) in solution to
      antibody (or antigen) immobilized on a biosensor surface is analyzed within a
      fractal framework. The data is adequately described by a single- or a dual
      fractal analysis. Initially, the data was modelled by a single-fractal analysis.
      If an inadequate fit was obtained then a dual-fractal analysis was utilized. The
      regression analysis provided by Sigmaplot, 1993 (Scientific Graphing Software:
      User's Manual. Jandel Scientific, San Rafael, CA) was utilized to determine if a
      single-fractal analysis is sufficient, or a dual-fractal analysis is required. In
      general, it is of interest to note that the binding rate coefficient and the
      fractal dimension exhibit changes in the same direction (except for a single
      example) for the antigen-antibody systems analyzed. Binding rate coefficient
      expressions as a function of the fractal dimension developed for the antigen
      antibody binding systems indicate a high sensitivity of the binding rate
      coefficient on the fractal dimension when both a single -as well as a dual
      fractal analysis is used. For example, for a single-fractal analysis and for the
      binding of human endothelin-1 (ET-1) antibody in solution to ET-1(15-21) x BSA
      (bovine serum albumin) immobilised on a surface plasmon resonance surface, the
      order of dependence of the binding rate coefficient, k on the fractal dimension,
      Df is 7.0945. Similarly, for a dual-fractal analysis and for the binding of
      parasite L. donovani diluted pooled sera in solution to fluorescein
      isothiocyanate-labeled anti-human immunoglobulin IgG immobilized on an optical
      fibre, the order of dependence of k1 and k2 on Df1 and Df2 were 6.8018 and 
      4.393, respectively. Binding rate coefficient expressions are also developed as a
      function of the analyte (antigen or antibody) concentration in solution. The
      binding rate coefficient expressions developed as a function of the fractal
      dimension(s) are of particular value since they provide a means to better control
      biosensor performance by linking it to the heterogeneity on the surface, and
      emphasize in a quantitative sense the importance of the nature of the surface in
      biosensor performance.

PMID- 11459098
TI  - Odorant detection capability of QCR sensors coated with plasma deposited organic
      films.
AB  - Odorant-detection experiments were conducted on major single-odor substances in
      various types of botanical species. The sensing devices we used were quartz
      crystal resonators (QCRs), radio-frequency (RF) sputtered with amino acids or
      polymers. The odorants were generated at very low concentrations (ppb level) by
      using the diffusion-tube method. The tested odorants were detected at
      concentrations between 0.3 and 940 ppb. These deposited films had high partition
      coefficients for the odorants, confirming their high sensitivity to organic
      vapors, especially to terpenoids. This indicates that the odorant solvation is
      due to odorant-film interaction related to Gibbs free energy.

PMID- 11459099
TI  - BIOSET: Biosensors for Environmental Technology EU Workshop 'Biosensors for
      Environmental Monitoring: Technology Evaluation'. Held in Kinsale, Ireland, 12-15
      May 1998.

PMID- 11459100
TI  - Development of renewable surface biosensors to meet industrial needs for
      measurement of glucose in fruit juices.
AB  - Most biosensors reported to date have been prepared, studied and used under
      laboratory conditions. The feasibility of a very great number of biosensors seems
      to be demonstrated and their characteristics, very often, established as
      corresponding to the demands of the modern analysis. The operational stability of
      the biosensors, according to authors, is almost always acceptable. The long term
      storage, with analytical quality conservation that is necessary to commercialise
      products, has rarely been studied. The stability of biosensors has to remain not
      only during the fabrication step or their subsequent utilisation, but also
      throughout the whole commercial shelf-life of the sensor, from producer to end
      user, through wholesaler and/or retailer. We developed the manufacturing
      processes, on a large scale, of renewable surface electrodes modified with
      enzymes such as oxidoreductases. The process consisting of several steps is
      described and the analytical behaviours of resulting biosensors is studied and
      correlated with the effects of different constraints applied during the
      fabrication process.

PMID- 11459101
TI  - Human GM-CSF interaction with the alpha-chain of its receptor studied using
      surface plasmon resonance.
AB  - A surface plasmon resonance (SPR) based biosensor has been used for studying the
      interaction of recombinant human granulocyte-macrophage colony-stimulating factor
      (GM-CSF) with genetically engineered alpha-chain subunits of its specific
      receptor (GM-Ralpha). Western blot analysis of GM-Ralpha confirmed the correct
      size (80 kDa) and reactivity of these proteins against anti-GM-Ralpha polyclonal
      or monoclonal antibodies. GM-CSF was immobilized, using standard amine coupling
      methods, to the dextran-modified gold biosensor surface in order to capture GM
      Ralpha subsequently injected over the sensing layer. GM-Ralpha were shown to
      specifically form complexes with the immobilized ligand. Pre-incubation of
      constant amounts of GM-Ralpha with dilutions of soluble GM-CSF before injection
      of the mixture over the GM-CSF matrix, prevented ligand binding in a dose
      dependent manner. In contrast, unrelated soluble cytokines or serum proteins
      (e.g. G-CSF, albumin, etc.) were found to exert no inhibition. Complexes
      formation blockage by pre-incubation of constant amounts of GM-Ralpha with
      dilutions of neutralizing anti-GM-Ralpha antibodies was concentration dependent,
      further assessing the specificity of the interaction. To investigate the
      possibility of relating the effect on binding affinity of critical conformational
      changes at the contact site, experiments of multisite binding were performed,
      flowing a set of neutralizing monoclonal antibodies reacting to different
      epitopes on GM-CSF over the GM-CSF matrix, before injecting GM-Ralpha. The
      results indicated that antibody interaction with helix D and helix A of GM-CSF
      markedly inhibited GM-CSF binding to GM-Ralpha. Comparable results were obtained
      using the biosensor technology and enzyme-linked immunoassays, in representative
      experiments performed with the same reagents. These experiments demonstrate that
      SPR can be successfully used for studying complementary interactions between GM
      CSF and its receptor alpha-chains in solution without using labels or secondary
      tracers and, compared with conventional immunoanalysis methods, significantly
      saving time.

PMID- 11459102
TI  - Determination of organophosphate and carbamate pesticides in spiked samples of
      tap water and fruit juices by a biosensor with photothermal detection.
AB  - The determination of organophosphate (paraoxon, chlorpyrifos, diazinon) and
      carbamate (carbaryl, carbofuran) pesticides in spiked drinking water and fruit
      juices was carried out using a photothermal biosensor. The biosensor consists of
      a cartridge containing immobilised enzyme acetylcholinesterase (AChE) placed in a
      flow-injection analysis (FIA) manifold and a photothermal detector based on
      thermal lens spectrometry. With this approach, 0.2 ng/ml of paraoxon can be
      detected in less than 15 min. Limits of detection for other organophosphate
      (chlorpyrifos, diazinon) and carbamate (carbaryl, carbofuran) pesticides varied,
      depending on their antiacetylcholinesterase (AntiAChE) toxicity, from 1 ng/ml to
      4 microg/ml. The biosensor was used for the direct detection of pesticides in
      spiked tap water and fruit juices without any pretreatment steps. In these cases,
      the LOD3sigma of 1.5, 2.8 and 4 ng/ml paraoxon in tap water, orange juice and
      apple juice were obtained, respectively.

PMID- 11459103
TI  - A ferric chloride pre-treatment to prevent calcification of Nafion membrane used
      for implantable biosensors.
AB  - Since the perfluorosulfonated ionomer Nafion, commonly used for the protection of
      biosensors, experiences calcification in a biological environment, we evaluated
      the efficacy of preincubating Nafion membranes in a FeCl3 solution to reduce the
      number of nucleation sites responsible for the growth of the calcium phosphate
      crystals. Nafion membranes were prepared and divided into two groups. In the
      first group, the Nafion membranes were pre-incubated in 0.1 M FeCl3 for a 24 h
      period. In the second group, no pre-incubation took place. All membranes were
      placed in a culture medium for a period of up to 4 weeks. All membranes were then
      examined for changes in: (1) their surface topography (using scanning electron
      microscopy (SEM)); (2) their near surface chemical properties (using energy
      dispersive X-ray (EDX)); and (3) their permeability to glucose. The membranes
      that were not pre-incubated in FeCl3 showed significant cracking of the Nafion
      surface, extensive calcium phosphate deposits and a resulting decrease in
      permeability. In contrast, the membranes treated with FeCl3 showed almost no
      cracking, very little calcium phosphate deposits and no change in permeability to
      glucose. This study demonstrated that FeCl3 significantly reduces calcification
      of Nafion and thus should help in preserving the in vivo function of implantable
      biosensors that utilize Nafion in their design.

PMID- 11459104
TI  - The use of regenerable, affinity ligand-based surfaces for immunosensor
      applications.
AB  - The regeneration of antibody-binding surfaces is of major importance for re
      usable sensor formats such as required for direct 'real-time' biosensing
      technologies and is often difficult to achieve. Antibodies commonly bind the
      antigen with high avidity and may themselves be sensitive to regeneration
      conditions. The interaction of polyclonal anti-chlorpyriphos antibody with an
      immobilised chlorpyriphos-ovalbumin (chlor-oval) conjugate and the interaction of
      soluble recombinant CD4 with covalently immobilised anti-CD4 IgG are presented in
      order to highlight these difficulties. Affinity-capture is suggested as an
      alternative format as it facilitates surface regeneration, directed
      immobilisation and the attainment of interaction progress curves that conform to
      the ideal pseudo-first-order kinetic interaction model. Protein A, protein G and
      polyclonal anti-mouse Fe-coated surfaces were used to observe the interaction of
      captured anti-GST monoclonal antibody with glutathione-s-transferase (GST). It
      was shown that a protein A affinity-capture surface produced ideal interaction
      progress curves while both protein G and polyclonal anti-mouse Fe resulted in
      systemic deviations.

PMID- 11459105
TI  - Detection of mild cognitive deficits in Parkinson's disease patients with the
      WAIS-R NI.
AB  - The relative insensitivity of traditional IQ tests to mild cognitive deficits has
      led investigators to develop a version of the widely used Wechsler intelligence
      scales that allows quantitative analysis of underlying qualitative responses.
      This instrument, the Wechsler Adult Intelligence Scale-Revised as a
      Neuropsychological Instrument (WAIS-R NI) was administered to 16 Parkinson's
      disease (PD) patients and 30 normal controls (NC). The 2 groups did not differ
      significantly in mean age or education, or on their mean Mattis Dementia Rating
      Scale score. Relative to NC participants, PD patients showed decreased visual
      attention span, longer response latencies, slower visuomotor processing, and more
      stimulus-bound errors. Many of the WAIS-R NI measures were able to detect
      cognitive impairment in a greater percentage of patients than the traditional
      WAIS-R measures, making it easier to identify deficits that could affect quality
      of life early in the course of the disease.

PMID- 11459106
TI  - A new verbal learning and memory test for English- and Spanish-speaking older
      people.
AB  - Word-list verbal learning and memory tests with appropriate normative data can be
      highly sensitive to cognitive decline, but there are significant limitations of
      such tests available for use with older Hispanic and non-Hispanic people living
      in the US. The purpose of this study was to (1) create a new word-list learning
      and memory test in both English and Spanish and, (2) validate it with respect to
      sensitivity to cognitive impairment, and (3) develop statistical corrections for
      the effects of significant demographic variables, including ethnicity, language
      of administration, age, education, and gender. A community dwelling sample of 801
      English- and Spanish-speaking older people was employed. Recall on learning
      trials and the delayed recall trial of the word-list learning test were strongly
      related to the Mini-Mental State Examination (MMSE). moderately related to age,
      and weakly related to gender and education. The relationship of word-list
      variables and the MMSE did not significantly differ across ethnicity/language
      groups. Regression coefficients for demographic variables were used in a
      statistical correction formula to adjust raw word-list scores, and then to
      develop specific percentile cut-off values.

PMID- 11459107
TI  - Where and what visuospatial processing in adolescents with congenital
      hypothyroidism.
AB  - Visuospatial processing is accomplished in distinct neuroanatomic pathways. One
      such pathway, known as the where pathway, involves a dorsal route through
      magnocellular thalamic cells to occipital and parietal cortices and conveys
      location and motion information. A second pathway, known as the what pathway,
      involves a ventral route through parvocellular thalamic cells to occipital and
      temporal cortices and conveys color and form information. The where pathway is
      thought to be responsible for processing spatial relationships while the what
      pathway is responsible for object identification. Children with early-treated
      congenital hypothyroidism (CH) who exhibit selective visuospatial deficits may
      provide a good model to study the differential development of these pathways.
      Because children with CH lacked thyroid hormone at a time when needed by
      developing brain regions such as the parietal cortex, these children may be
      affected to a greater degree on tasks tapping where but not what pathway
      processing. We tested this hypothesis via retrospective analysis of their
      performance on 6 spatial tasks. Compared were 49 adolescents with CH and 49
      matched control participants. On the basis of confirmatory factor analysis, tasks
      were assigned to either where or that pathway groupings. A repeated measures
      ANOVA showed the CH group was impaired relative to a normal comparison group only
      on where pathway tasks. Regression analyses indicated that severity of early
      hypothyroidism was the strongest predictor of where pathway processing but had no
      effect on what pathway tasks. It is concluded that thyroid hormone is required
      during late gestation and early life for the normal development of the where
      aspects of visuospatial processing.

PMID- 11459108
TI  - Differential episodic and semantic memory performance in Alzheimer's disease and
      vascular dementias.
AB  - Differential performance on measures of episodic and semantic memory were
      examined in AD, cortical vascular dementia (CVaD), subcortica] vascular dementia
      (SVaD), and controls. Groups were matched on age, education, and gender; dementia
      groups also were matched on severity. Recognition/retrieval differences were
      found only between SVaD and AD groups, not between CVaD and AD. Thus,
      recognition/retrieval differences are likely secondary to subcortical pathology
      rather than to vascular etiology per se. Similarly, significant numbers of memory
      errors were associated with cortical pathology, regardless of etiology. Error
      rate differences were found only between SVaD and AD groups, not between CVaD and
      AD. Finally, rapid forgetting was unique to AD; however, since no difference was
      found between SVaD and AD, rapid forgetting may occur only as AD progresses. No
      semantic memory measure differentiated AD from either CVaD or SVaD subjects.
      Results suggest that some previously reported episodic differences may be due to
      cortical versus white matter subcortical pathology, rather than to AD versus
      vascular etiology.

PMID- 11459109
TI  - Patterns of verbal learning and memory in traumatic brain injury.
AB  - CVLT and WMS-R Digit Span variables were used to calculate indexes of seven
      specific short- and long-term memory processes: working memory span and central
      executive functions, and long-term memory encoding, consolidation, retention,
      retrieval, control abilities. Scores on these indexes were then cluster-analyzed
      to determine whether subtypes of memory performance exist that correspond to
      deficits in these theoretical memory constructs. Parallel analyses were conducted
      with two large samples (N = 150 and N = 151) of individuals who had sustained a
      traumatic brain injury (TBI). Findings showed that TBI results in subgroups of
      memory disorders with specific deficits in consolidation, retention, and
      retrieval processes. Control problems (keeping track of list versus non-list
      items) only appeared in conjunction with retrieval deficits. Working memory span
      and central executive functioning (i.e., the ability to manipulate information in
      working memory) do not appear to be deficits characteristic of TBI as no such
      clusters emerged in the analyses. By using specific indexes of memory processes,
      and in contrast to previous studies, patterns of memory dysfunction were found
      that correspond to deficits in theoretically meaningful memory constructs.

PMID- 11459110
TI  - Verbal and design fluency in patients with frontal lobe lesions.
AB  - The ability to generate items belonging to categories in verbal fluency tasks has
      been attributed to frontal cortex. Nonverbal fluency (e.g., design fluency) has
      been assessed separately and found to rely on the right hemisphere or right
      frontal cortex. The current study assessed both verbal and nonverbal fluency in a
      single group of patients with focal, frontal lobe lesions and age- and education
      matched control participants. In the verbal fluency task, participants generated
      items belonging to both letter cues (F, A, and S) and category cues (animals and
      boys' names). In the design fluency task, participants generated novel designs by
      connecting dot arrays with 4 straight lines. A switching condition was included
      in both verbal and design fluency tasks and required participants to switch back
      and forth between different sets (e.g., between naming fruits and furniture). As
      a group, patients with frontal lobe lesions were impaired, compared to control
      participants, on both verbal and design fluency tasks. Patients with left frontal
      lesions performed worse than patients with right frontal lesions on the verbal
      fluency task, but the 2 groups performed comparably on the design fluency task.
      Both patients and control participants were impacted similarly by the switching
      conditions. These results suggest that verbal fluency is more dependent on left
      frontal cortex, while nonverbal fluency tasks, such as design fluency, recruit
      both right and left frontal processes.

PMID- 11459111
TI  - Test-retest bias, reliability, and regression equations for neuropsychological
      measures repeated over a 12-16-week period.
AB  - The interpretation of neurobehavioral change over time requires knowledge of the
      test-retest characteristics of the measures. Without this information it is not
      possible to distinguish a true change (i.e., one reflecting the occurrence or
      resolution of an intervening process) from that occurring on the basis of chance
      or systematic bias. We tested a group of 72 healthy young to middle aged adults
      twice over a 12-to-16-week interval in order to observe the change in scores over
      time when there was no known intervention. The test battery consisted of seven
      commonly used cognitive measures and the Profile of Mood States (POMS). Test
      retest regression equations were calculated for each measure using initial
      performance, age, education, and a measure of general intellectual function
      (Wonderlic Personnel Test) as regressors. Test-retest correlations ranged from
      .39 (POMS Fatigue) to .89 (Digit Symbol). Cognitive measures generally yielded
      higher correlations than did the POMS. Univariate regressions based only on
      initial performance adequately predicted retest performance for the majority of
      measures. Age and education had a relatively minor influence. Practice effects
      and regression to the mean were common. These test-retest regression equations
      can be used to predict retest scores when there has been no known intervention.
      They can also be used to generate statistical statements regarding the
      significance of change in an individual's performance over a 12-to-16-week
      interval.

PMID- 11459112
TI  - Asymmetrical hand force persistence and neuroleptic treatment in schizophrenia.
AB  - The recent development of an isometric instrument for the precise quantification
      of hand force persistence has created a novel opportunity for the evaluation of
      potential motor asymmetries in schizophrenia and their response to treatment. A
      study of asymmetries in the unmedicated state may provide insight into the
      pathogenesis of schizophrenia, whereas alterations of asymmetries in response to
      antipsychotic medication could assist the delineation of a cerebral mechanism for
      the effects of pharmacotherapy. The hand force persistence of 21 unmedicated
      patients with schizophrenia was compared to 21 age, gender, and handedness
      matched normal controls. The effect of neuroleptic treatment on hand force
      persistence was then evaluated on a subset of 10 patients after at least 30 days
      of treatment. The anticipated asymmetry was evident in the unmedicated sample
      that showed impaired right hand force persistence compared to the normal control
      sample. The prospective comparison showed an alleviation of the asymmetry
      resulting from an improvement of right hand force persistence with treatment. In
      addition to providing further support to a primary left hemisphere cerebral
      involvement in schizophrenia, the present results suggest that prior
      investigations of motor asymmetry may have been compromised by the study of
      medicated patients. The apparently paradoxical improvement of motor skill may
      relate to the substantial number of patients treated with 2nd generation
      neuroleptic medications which may implicate an improvement in left hemisphere
      physiology in the cognitive advantages of the novel treatments.

PMID- 11459113
TI  - Acquisition of skilled visual search performance following severe closed-head
      injury.
AB  - This study used a semantic-category visual search task to investigate skill
      acquisition and automatic process development in a severe closed-head injured
      (CHI) population. Eighteen severe CHI participants (> I year post injury) and 18
      matched controls completed over 3600 trials of training in both consistent
      mapping (CM) and varied mapping (VM) training situations. Transfer conditions
      were also used to test for development of an automatic attention response (AAR)
      that was independent of general, task-related learning. For both the severe CHI
      and control group, CM training, where individuals always responded in the same
      way to a specific class of stimuli, resulted in dramatic performance improvements
      and the development of an AAR. In the VM training condition, where individuals
      could not respond in the same way to a class of stimuli from one stimulus
      exposure to the next, there was little performance improvement and continued
      reliance on controlled processes. The visual search rates of the CHI participants
      also remained slower than those of controls following extended VM but not
      extended CM practice. These results indicate that skill acquisition training
      guidelines can be used to teach severe CHI patients to develop a new automatic
      skill.

PMID- 11459114
TI  - Preclinical prediction of AD using neuropsychological tests.
AB  - Normals (N = 42) and patients with mild memory difficulty (N = 123) were given a
      neuropsychological test battery, and then followed annually for 3 years to
      determine which individuals developed sufficient functional change that they met
      clinical criteria for AD. Twenty-three of the 123 participants with mild memory
      difficulty converted to a diagnosis of probable Alzheimer's disease (AD) within 3
      years of follow-up. Four of the 20 neuropsychological measures obtained at
      baseline, were useful in discriminating the groups on the basis of their status 3
      years after the tests were given. The 4 discriminating tests pertained to
      assessments of memory and executive function. When the controls were compared to
      the individuals with memory impairments who ultimately developed AD (the
      converters), the accuracy of discrimination was 89%, based on the
      neuropsychological measures at baseline. The discrimination of the controls from
      the individuals with mild memory problems who did not progress to the point where
      they met clinical criteria for probable AD over the 3 years of follow-up (the
      Questionables) was 74% and the discrimination of the questionables from the
      converters was 80%. The specific tests that contributed to these discriminations,
      in conjunction with recent neuropathological and neuroimaging data from
      preclinical cases, have implications for which brain regions may be affected
      during the prodromal phase of AD.

PMID- 11459115
TI  - Verbal memory deficits associated with fornix atrophy in carbon monoxide
      poisoning.
AB  - Magnetic resonance (MR) images and neuropsychological testing data of 69 carbon
      monoxide (CO) poisoned patients were prospectively obtained within 1 day of CO
      poisoning, two weeks and six months. CO patients' Day 1 cross-sectional fornix
      surface area measurements, corrected for head size by using a fornix-to-brain
      ratio (FBR), were compared to normal age and gender-matched controls.
      Additionally, a within-subjects analysis was performed comparing the mean areas
      between CO patients' Day 1, 2 weeks and 6-month FBR. The FBR was correlated with
      patients' neuropsychological data. There were no significant differences between
      CO patients' Day 1 fornix measurements compared to normal control subjects.
      However, significant atrophic changes in the fornix of CO poisoned patients
      occurred at two weeks with no progressive atrophy at 6 months. By 6 months, CO
      patients showed significant decline on tests of verbal memory (when practice
      effects were taken into account), whereas visual memory, processing speed and
      attention/concentration did not decline. This study indicates that CO results in
      brain damage and cognitive impairments in the absence of lesions and other
      neuroanatomic markers.

PMID- 11459116
TI  - Estrogen and cerebrovascular physiology and pathophysiology.
AB  - Numerous studies have uncovered a wide variety of estrogen effects with apparent
      cardiovascular benefits, the most recognized ones being vasodilation, anti
      atherogenesis, diminished post-ischemic inflammation and anti-oxidant effects.
      This article provides an overview of the influence of estrogen on the cerebral
      vasculature, under physiologic and pathophysiologic conditions, and covers both
      acute and chronic effects. The discussion is primarily focused on the
      vasodilatory and anti-inflammatory actions of estrogen, since those particular
      estrogen influences have received the greatest attention in studies published to
      date. With respect to vasodilation, although some consideration is given to the
      role of other vasodilating mechanisms and factors, the emphasis is mostly placed
      on the endothelial isoform of nitric oxide synthase, eNOS, which has emerged as a
      clear target of estrogen. Some consideration is given to recent findings that
      suggest that estrogen can stimulate eNOS activity by decreasing the expression of
      the eNOS inhibitor caveolin-1. With regard to the ability of estrogen to
      counteract inflammation, potential mechanisms by which estrogen limits the post
      ischemic leukocyte adhesion, and the expression of the inducible NOS, are
      discussed.

PMID- 11459117
TI  - Adrenomedullin inhibits the pressor effects and decrease in renal blood flow
      induced by norepinephrine or angiotensin II in anesthetized rats.
AB  - Adrenomedullin (AM), a hypotensive peptide originally isolated from human
      pheochromocytoma, has been reported to regulate renal functions. In patients with
      glomerulonephritis, the serum levels of AM are elevated as well as hypertensive
      agents norepinephrine (NE) and angiotensin II (AII). The effects of AM on the NE-
      or AII-induced pressor effects and renal blood flow responses, however, are not
      well clarified. We examined the effects of AM on blood pressure and renal blood
      flow induced by NE or AII in anesthetized rats. Arterial blood pressure and renal
      blood flow were measured using a calibrated pressure transducer and a laser
      Doppler flowmeter, respectively. Drugs were injected into the tail vein with a
      syringe. Intravenous administration of AM (1-3 nmol/kg) decreased the arterial
      blood pressure in anesthetized rats in a dose-dependent manner, whereas it did
      not affect the renal blood flow. NE or AII administration in anesthetized rats
      caused both increases in blood pressure and decreases in renal blood flow.
      Simultaneous administration of AM with NE or All prevented the increasing effects
      of blood pressure and inhibited the decreases in renal blood flow caused by NE or
      AII. These findings suggest that AM may have a protective role against the
      pressor effects and decrease in renal blood flow caused by NE or AII.

PMID- 11459118
TI  - Effect of TAK-637, a tachykinin NK1-receptor antagonist, on lower urinary tract
      function in cats.
AB  - The effect of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,11
      tetrahydro-9-methyl-5-(4-methylphenyl)-7H[1,4]diazocino[2,1g][1,7]naphthyridine
      6,13-dione), a tachykinin NK1-receptor antagonist, on lower urinary tract
      function was investigated in cats. TAK-637 (0.1, 0.3, 1 and 3 mg/kg, i.v.)
      produced a dose-dependent increase in bladder capacity without any significant
      reduction in voiding efficiency in decerebrate cats. The maximal increase in
      bladder capacity was 94%. By contrast, oxybutynin at 1 and 3 mg/kg (i.v.)
      produced a 18% and 35% increase in bladder capacity, respectively, with a 47% and
      45% reduction in voiding efficiency. TAK-637 (3 mg/kg, i.v.) did not inhibit the
      micturition reflex induced by electrical stimulation of the rostral brainstem
      near the locus coeruleus, indicating that it does not impair the well-organized
      micturition reflex (bladder contraction and urethral relaxation). These results
      suggest that TAK-637 increases bladder storage capability without inhibiting the
      voiding function of the lower urinary tract, presumably by inhibiting the
      afferent pathway of the micturition reflex, rather than the efferent pathway.

PMID- 11459119
TI  - Markedly increased nasal blockage by intranasal leukotriene D4 in an experimental
      allergic rhinitis model: contribution of dilated mucosal blood vessels.
AB  - We examined whether nasal hyperresponsiveness to leukotriene (LT) D4 is seen in
      our allergic rhinitis model, which showed sneezing and biphasic nasal blockage by
      repeated antigen inhalation challenge, and whether a dilatation of mucosal blood
      vessels contributes to this hyperresponsiveness. Nasal blockage [increase of
      specific airway resistance (sRaw)] was indexed as nasal (hyper)responsiveness.
      The sensitized-challenged guinea pig showed a remarkable dose-dependent increase
      in sRaw by intranasal instillation of LTD4 (10 microl/nostril) at 10(-10) to 10(
      6) M 10 h and 2 days but not 7 days after the challenge. The increase in sRaw
      induced by LTD4 was largely blocked by pranlukast or naphazoline, and this was
      dose-dependently suppressed by N(omega)-nitro-L-arginine methyl ester. Sodium
      nitroprusside induced an elevation of sRaw in the sensitized-challenged animal in
      the hyperresponsiveness state, but the degree did not differ from that in the non
      sensitized-non-challenged group. The amount of NO2- and NO3- in nasal cavity
      lavage fluid after LTD4 instillation in the sensitized-challenged animal in the
      hyperresponsiveness state was significantly greater than that before the
      instillation. These results demonstrate that the hyperresponsiveness to LTD4
      acquired by repeated antigen challenge is mainly due to dilatation of nasal blood
      vessels, which can be related to hyperproduction of nitric oxide through
      cysteinyl LT1-receptor activation.

PMID- 11459120
TI  - Long term effects of Toki-shakuyaku-san on brain dopamine and nerve growth factor
      in olfactory-bulb-lesioned mice.
AB  - We used olfactory-bulb-lesioned mice induced by intranasal irrigation with zinc
      sulfate as a model of dementia, to investigate the effects of Toki-shakuyaku-san
      (TSS) on monoamines and nerve growth factor (NGF) in brain regions. TSS was given
      daily through the drinking water for either 1, 2, 3, 4 or 8 weeks from the day
      after olfactory lesion. The administration of TSS significantly suppressed the
      decrease of 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA)
      in olfactory bulb of olfactory-lesioned mice at 1 week, and tended to suppress
      the decrease of DOPAC and HVA during the experimental session. However, the
      administration of TSS had no influence on dopamine contents. NGF contents in the
      olfactory bulb were increased after the irrigation, and the value returned to the
      same level as the control at 8 weeks after. Although the NGF contents in the
      olfactory bulb of TSS-treated mice were immediately increased at 1 and 2 weeks,
      the value returned to normal level within 3 weeks. These findings indicate that
      oral administration of TSS prevents the reduction of dopamine metabolites, DOPAC
      and HVA, and immediately increased NGF contents in the olfactory bulb. This
      suggested that TSS treatment promotes the NGF contents in olfactory nerves and
      rescue the neurons from damage.

PMID- 11459121
TI  - Affinity of serotonin receptor antagonists and agonists to recombinant and native
      alpha1-adrenoceptor subtypes.
AB  - Binding affinities of serotonin (5-HT)-receptor antagonists and agonists at human
      recombinant alpha1-adrenoceptor subtypes (alpha1a-, alpha1b- and alpha1d
      subtypes) were examined and compared with the functional affinities obtained in
      rat caudal artery (alpha1A-subtype), dog carotid artery (alpha1B-subtype) and rat
      thoracic aorta (alpha1D-subtype). Most of the 5-HT-receptor antagonists and
      agonists tested showed relatively high affinity to three alpha1-adrenoceptor
      subtypes. The highest affinity close to 1 nM was seen for NAN-190 (5-HT1A
      antagonist) in binding and functional studies. 5-Methylurapidil (5-HT1A agonist)
      and BMY7378 (5-HT1A agonist) showed, respectively, alpha1a(alpha1A)- or
      alpha1d(alpha1D)-subtype selectivity in both binding and functional affinities,
      but spiperone (5-HT2A antagonist) showed alpha1b-selectivity only in binding
      affinity. Functional affinity of ritanserin (5-HT2A antagonist) to the alpha1B
      subtype was approximately 500-fold lower than that of affinity to the alpha1b
      subtype. The present results show that many 5-HT-receptor antagonists and
      agonists have high affinity to alpha1-adrenoceptors, but suggest that there is
      deviation between their functional affinities and binding affinities for some
      drugs.

PMID- 11459122
TI  - Involvement of neuropeptides in the allergic nasal obstruction in guinea pigs.
AB  - The purposes of the present study were i) to determine whether neuropeptides
      induce the nasal obstruction in guinea pigs, and ii) to examine the possible
      involvement of neuropeptides in allergic nasal obstruction. The decrease in nasal
      cavity volume was determined by acoustic rhinometry as an index of nasal
      obstruction. In non-sensitized guinea pigs, substance P (SP), neurokinin A (NKA)
      and calcitonin gene-related peptide (CGRP) caused the nasal obstruction 10 to 30
      min after their intranasal application. LY303870 (1 mg/kg), a tachykinin NK1
      receptor antagonist; SR48968 (1 mg/kg), a tackykinin NK2-receptor antagonist; and
      CGRP(8-37) (50 nmol/kg), a CGRP1-receptor antagonist, administered intravenously
      before the intranasal application of the neuropeptides, inhibited the responses
      induced by SP, NKA and CGRP, respectively. In the guinea pigs sensitized with
      dinitrophenyl-coupled Ascaris suum allergenic extract, the intranasal antigen
      challenge caused nasal obstruction. The response was biphasic and consisted of
      the early phase response (EPR) and the late phase response (LPR), which developed
      30 min and 6 h, respectively, after the antigen challenge. Intravenous
      administration of LY303870 (1 mg/kg) before the antigen challenge inhibited the
      EPR, while those of SR48968 (1 mg/kg) and CGRP(8-37) (50 nmol/kg) inhibited the
      LPR. The present results suggest that neuropeptides are involved in the allergic
      nasal obstruction.

PMID- 11459123
TI  - Possible roles of cardiac chymase after myocardial infarction in hamster hearts.
AB  - The significance of cardiac chymase after myocardial infarction (MI) was
      evaluated using a hamster model of MI. At 1, 3, 7, 14, 28 and 56 days after MI,
      tissues were removed for measurements of angiotensin-converting enzyme (ACE) and
      chymase activities. The mean infarct size 3 days after left coronary artery
      ligation was 47.3 +/- 5.9% of the left ventricle circumference. The ratio of left
      ventricle weight to body weight was significantly increased from 3 days after MI.
      The level of plasma renin activity in the MI hamsters was significantly increased
      at the early phase of MI (1-3 days), while no significant changes in plasma ACE
      activity were observed. The ACE activity in the infarcted left ventricle was
      significantly increased starting from 3 days after MI and this increase was
      sustained up to 28 days. The chymase activity in the infarcted left ventricle was
      significantly increased starting from 1 day after MI and this increase was
      sustained up to 56 days. The number of chymase-positive mast cells in the
      infarcted left ventricle was significantly higher than in the sham group 3 and 7
      days after operation. Treatment with an angiotensin (Ang) II type 1 receptor
      antagonist (candesartan cilexetil, 10 mg/kg per day) starting 3 days before the
      induction of MI significantly reduced the mortality rate during 14 days of
      observation following MI, whereas treatment with an ACE inhibitor (lisinopril, 20
      mg/kg per day) did not. A significant improvement in hemodynamics (maximal
      negative and positive rates of pressure development, left ventricular systolic
      pressure and end-diastolic pressure, mean arterial blood pressure) was observed
      by the treatment with candesartan cilexetil, but not with lisinopril, 3 and 14
      days after MI. These results suggested that Ang II produced by chymase may
      participate in the pathophysiologic state after MI in hamsters.

PMID- 11459124
TI  - Enhancement of phenylephrine-induced contraction in the isolated rat aorta with
      endothelium by H2O-extract from an Oriental medicinal plant Leonuri herba.
AB  - Leonuri herba (I-mu-ts'ao, the Chinese motherwort) is an ancient Chinese
      traditional herb. Although the pharmacological effects of extracts of Leonuri
      herba have been shown in platelets and uteri, the effect on the vascular system
      has not been determined. In the present study, we investigated the effects of
      extracts of Leonuri herba on the contraction of the isolated rat aorta. Although
      the H20-extract (0.3-3 mg/ml) by itself showed a limited effect, the extract
      enhanced phenylephrine-induced contraction of the aorta with endothelium, but not
      without endothelium. The H20-extract, like N(G)-nitro-L-arginine methyl ester (L
      NAME, an inhibitor of nitric oxide synthase), significantly inhibited the
      relaxation induced by acetylcholine in the aorta with endothelium. The inhibitory
      effect of H20-extract on the relaxation decreased by co-addition with 1 mM L
      arginine. The vasoconstrictive effect of H20-extract was not due to leonurine,
      which is a constituent in Leonuri herba and shows uterotonic activity.
      Intravenous injection of the H20-extract (1.5 mg/kg) to rats caused an increase
      in blood pressure for 5 min, like L-NAME (1.35 mg/kg). These findings suggest
      that there is a component(s) in Leonuri herba, which shows a vasoconstrictive
      activity in rat aorta in vitro and in vivo and has similar pharmacological
      profile to that of L-NAME.

PMID- 11459125
TI  - Structure-activity relationships of triterpenoid derivatives extracted from
      Gymnema inodorum leaves on glucose absorption.
AB  - The leaves of Gymnema inodorum (GI) have been known to be effective for some
      diseases including diabetes mellitus, rheumatic arthritis and gout. The crude
      saponin mixtures extracted from GI leaves inhibited glucose absorption in the
      isolated intestinal tract and suppressed the increased blood glucose in rats. In
      this study, we examined the relationship between chemical structure and
      pharmacological activity of the four components from GI leave extracts (GiA-1,
      GiA-2, GiA-5 and GiA-7). These components were the derivatives of
      (3beta,4alpha,16beta)-16,23,28-trihydroxyolean-12-en-3-yl-beta-D
      glucopyranosiduroic acid. GiA-2, GiA-5 and GiA-7 that have suppressive effects on
      the high K+-induced contraction, an increase in deltaPD and the increased blood
      glucose level in the glucose tolerance test have -H at the 21st position and 
      CH2OH at 4beta of aglycon. On the other hand, GiA-1 that does not have any
      effects on the three parameters mentioned above has -H at the 21st position and 
      CH3 at 4beta of aglycon. In conclusion, it is suggested that the inhibitory
      effect of triterpenoids in Gymnema leaves on glucose absorption from the
      intestinal tract relies on -CH2OH at 4beta.

PMID- 11459126
TI  - NO-flurbiprofen attenuates excitotoxin-induced brain inflammation, and releases
      nitric oxide in the brain.
AB  - Brain inflammation underlies the pathogenesis of Alzheimer's disease (AD) and
      nonsteroidal anti-inflammatory drug therapy may delay the onset of AD. We
      investigated, in vivo, the effects of NO-flurbiprofen on brain inflammation in
      rats injected with quisqualic acid into the nucleus basalis and on the release of
      nitric oxide from the drug in naive rat brains. We showed that the excitotoxin
      induced microglia reaction, the expression of inducible nitric oxide synthase
      positive cells and the production of interleukin-1beta and prostaglandin-E2 in
      the injected area were attenuated by the NO-flurbiprofen (15 mg/kg, p.o.)
      treatment. An oral administration of NO-flurbiprofen (25, 50 and 100 mg/kg) to
      naive rats was followed by significant increases in cortical nitrite levels. This
      drug may have important therapeutic implications for the treatment of AD.

PMID- 11459127
TI  - Involvement of nitric oxide and vasoactive intestinal peptide in the
      nonadrenergic-noncholinergic relaxation of the porcine retractor penis muscle.
AB  - Neurotransmitters mediating nonadrenergic-noncholinergic (NANC) relaxation were
      investigated in strips of porcine retractor penis muscle (RPM). Muscle tone was
      raised by phenylephrine (1 microM) in the presence of atropine (1 microM) and
      guanethidine (50 microM). Upon electrical field stimulation (1 ms, 80 V, 1-32 Hz
      for 10 s), the initial fast relaxation was followed by the slow relaxation.
      Although the fast and the slow relaxation were completely abolished by
      tetrodotoxin (1 microM), they showed different pharmacological sensitivities to
      the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester
      (L-NAME, 0.1 mM). The fast relaxation was markedly inhibited by L-NAME in an L
      arginine reversible manner and by oxyhemoglobin (50 microM), while the slow
      relaxation was hardly blocked by L-NAME. L-NAME and alpha-chymotrypsin (alpha-CT,
      3 U/ml) selectively inhibited the fast and the slow relaxation, respectively.
      Alpha-CT abolished L-NAME-resistant slow relaxation, and L-NAME completely
      abolished the alpha-CT-resistant fast relaxation. Alpha-CT-resistant relaxation
      was not significantly different from the digitally calculated L-NAME-sensitive
      component, and L-NAME-resistant relaxation was similar to the digitally
      calculated alpha-CT-sensitive component. Vasoactive intestinal peptide (VIP,
      0.003-0.1 microM) relaxed porcine RPM in a concentration-dependent manner. The
      effect of a VIP was partially inhibited by a VIP receptor antagonist, VIP(10-28)
      (1 and 3 microM). L-NAME-resistant relaxation was also reduced by VIP(10-28) (3
      microM) and by another putative antagonist, VIP(6-28) (1 microM), although the
      effects of the two antagonists were somewhat inconsistent. From the histochemical
      staining, it was verified that nerve bundles that showed VIP-like
      immunoreactivities were also positive for the NADPH diaphorase reaction. These
      results suggest that NO and peptide neurotransmitter(s) including VIP mediate the
      NANC relaxation in porcine RPM.

PMID- 11459128
TI  - GTP gamma S-induced Ca2+ activated Cl- currents: its stable induction by Gq alpha
      overexpression in Xenopus oocytes.
AB  - In native Xenopus oocytes, injection of guanosine 5'-O-(3-thiotriphosphate)
      (GTPgammaS) (30 mM, 5 nl) did not induce Cl- current in 11 out of 22 oocytes.
      Injection of increased concentration of GTPgammaS (100 mM, 5 nl) into the oocytes
      induced Cl- currents in 16 out of 17 oocytes; however, the size of the induced
      currents was extremely varied. In oocytes overexpressing Gq alpha, GTPgammaS (30
      mM, 5 nl) faithfully evoked Ca2+-activated Cl- currents. These results indicate
      that heterogeneous expression of Gq alpha in Xenopus oocytes provides a useful
      system for studying the functional roles of Gq alpha in regulating cellular
      events.

PMID- 11459129
TI  - Dominant anti-vagal effect of pentobarbital on cardiac responses to intracardiac
      autonomic nerve stimulation in the dog.
AB  - The isolated canine atrium was perfused by heparinized blood of the donor dog. An
      adequate dose of pentobarbital that induced a potent hypotension in the donor did
      not produce any significant change in the atrial rate and developed tension in
      the isolated atrium perfused with donor's blood. Pentobarbital in doses that
      modified neither cardiac responses to intracardiac adrenergic nerve stimulation
      nor exogenously given norepinephrine or acetylcholine significantly inhibited
      intracardiac vagal responses. From these results, it is concluded that a large
      dose of pentobarbital has a dominant antivagal effect in the heart.

PMID- 11459130
TI  - Diltiazem ameliorates contractile dysfunction without shortening of action
      potential duration in ischemic heart of anesthetized dogs.
AB  - The purpose of the following experiment was to determine whether amelioration of
      myocardial contractile dysfunction by diltiazem is mediated by shortening of
      monophasic action potential duration (MAPD) during myocardial ischemia in
      anesthetized dogs. Diltiazem improved regional contraction during reperfusion
      after 10-min occlusion. The shortening of MAPD and increase in [K+]e were blunted
      by treatment with diltiazem. These results suggest that shortening of action
      potential duration during myocardial ischemia is unlikely to be a reason for the
      amelioration of contractile dysfunction.

PMID- 11459131
TI  - Effects of adenosine A1- and A2A-receptor agonists on enhancement of dopamine
      release from the striatum in methamphetamine-sensitized rats.
AB  - We report here both adenosine A1- and A2A-receptor agonists inhibit the
      expression of methamphetamine (MAP)-induced behavioral sensitization in rats.
      Animals were treated with MAP (1.0 mg/kg, i.p.) every 3 days with a total of 5
      administrations. The augmentation of dopamine release from the striatum was
      demonstrated by MAP re-administration (0.5 mg/kg, i.p.) after 7-day withdrawal by
      microdialysis. The augmentation of dopamine release was inhibited by pre
      treatment not with N6-cyclohexyladenosine (0.01 mg/kg, i.p.) but by with 2-p-(2
      carboxyethyl)phenethylamino-5'-N-ethylcarboxy-amide adenosine (0.1 mg/kg, i.p.).
      These results suggested that adenosine A1 and A2A receptors play an inhibitory
      role in sensitization via different mechanisms.

PMID- 11459132
TI  - Inhibitory effect of olopatadine hydrochloride on the sneezing response induced
      by intranasal capsaicin challenge in guinea pigs.
AB  - To investigate the possible inhibitory effect of olopatadine hydrochloride
      (olopatadine), an antiallergic drug, on the tachykinin-mediated nasal responses,
      we examined the effect of olopatadine on the sneezing and the nasal rubbing
      responses induced by intranasal capsaicin challenge in guinea pigs. Olopatadine
      (10 mg/kg, p.o.) inhibited the sneezing response by 57% without affecting the
      nasal rubbing one. The antihistamines chlorpheniramine and clemastine did not
      affect the responses. Morphine caused the inhibition of both responses, which was
      antagonized by naloxone. These results suggest that olopatadine inhibits the
      sneezing response by the inhibition of the tachykinin release and not by its
      antihistaminic action.

PMID- 11459133
TI  - Endothelium-dependent relaxation in response to low concentrations of bradykinin
      is enhanced by phosphoramidon, bosentan and BQ-123 in bovine coronary arteries in
      vitro.
AB  - An endothelin (ET)-converting enzyme inhibitor phosphoramidon (10 microM), an
      ET(AB)-receptor antagonist bosentan (10 microM) and an ET(A)-receptor antagonist
      BQ-123 (1 microM) potentiated endothelium-dependent relaxation of bovine coronary
      arteries in response to bradykinin (BK) at femtomolar to picomolar
      concentrations, but not at nanomolar concentrations. BQ-788 (3 microM), an ET(B)
      receptor antagonist, showed no significant effects on fM-nM BK-induced
      relaxation. These results suggest that the endothelium-dependent relaxation of
      isolated bovine coronary arteries induced by very low concentrations of BK is
      partly regulated by a complex mechanism involving the ET(A)-receptor antagonism.

PMID- 11459134
TI  - Study of fungicidal and antibacterial effect of the Cu(II)-complexes of thiophene
      oligomers synthesized in ZSM-5 zeolite channels.
AB  - The influence of the Cu(II)-complexes of thiophene oligomers synthesized by
      oxidative polymerization of thiophene with Cu2+ ions in ZSM-5 zeolite channels on
      fungicidal and antimicrobial properties was studied. It has been found that the
      heterogeneous system culture medium-modified zeolite increases sporulation of the
      tested fungus (Aspergillus niger) and concurrently kills yeast (Candida
      albicans). These effects are attributed to a slow release of Cu2+ ions and
      thiophene oligomers into the culture medium. As for the tested bacteria (G+
      Staphylococcus aureus, G- Escherichia coli), the percentage of the killed cells
      increases due to light activation of the system. The light effect is assigned to
      photogeneration of the reactive oxygen species (ROS), mainly *OH radicals, which
      were registered in the water solution by EPR spectroscopy. It has been confirmed
      that the thiophene oligomers present in the Cu-ZSM-5 microstructure slow down the
      release of copper into the medium.

PMID- 11459135
TI  - Metallothionein induction and condition index of dogwhelks Nucella lapillus (L.)
      exposed to cadmium and hydrogen peroxide.
AB  - It has been suggested that metallothionein (MT) not only can regulate essential
      metals and detoxify toxic metals, but that MT can also play a significant role as
      an antioxidant and can be induced by oxidative stresses other than metals. This
      study is aimed at investigating the effect of hydrogen peroxide (H2O2), and the
      combined effect of H2O2 and cadmium (Cd) on MT induction and condition index (CI)
      in dogwhelks Nucella lapillus. Adult male dogwhelks (27 +/- 1 mm in shell length)
      were exposed for 20 days to (1) control (filtered natural seawater only); (2),
      0.50 ppm Cd; (3) 2.0 ppm H2O2 + 0.50 ppm Cd; (4) 1.0 ppm H2O2 + 0.25 ppm Cd; (5)
      2.0 ppm H2O2; (6) 1000 ppm H2O2 or (7) 1000 ppm H2O2 + 0.50 ppm Cd. The
      concentration of MT in the Leiblein gland of N. lapillus was quantified using the
      silver saturation method. MT or MT-like proteins in the animals were induced by
      Cd (0.5 ppm), H2O2 (2.0 ppm) or Cd + H2O2, indicating that MT in this gastropod
      species can be induced by either metal or oxidative stresses. Exposure to high
      H2O2 (1000 ppm) alone or combined with Cd, and exposure to Cd (0.50 ppm) or H2O2
      (2.0 ppm), resulted in significant weight loss, indicated by a reduction of CI.
      However, CIs of groups (3) and (4) were similar to that of the control suggesting
      that Cd antagonistically reduces toxicity caused by H2O2 since Cd-induced MT may
      have a protective function against hydroxyl radicals.

PMID- 11459136
TI  - Organochlorine insecticides, polychlorinated biphenyls, and metals in water,
      sediment, and green frogs from southwestern Michigan.
AB  - In an attempt to explain the etiology of frog deformities and population
      declines, many possible causative factors have been examined, including the input
      of synthetic chemicals into aquatic systems, where frogs spend much of their
      lives, including their entire developmental stages. Deformities in populations of
      green frogs in wetlands of southwestern Michigan that are influenced by
      agricultural, urban, or industrial inputs were assessed in this study. Of the
      1445 green frogs (Rana clamitans) examined, only four (0.3%) exhibited
      morphological deformities. This deformity rate is less than the recognized
      background level of deformities for this species, which is approximately 1%.
      Concentrations of organochlorine insecticides, polychlorinated biphenyls (PCBs),
      and metals were determined in water, sediment, frog eggs, tadpoles, and adult
      green frog tissues. Concentrations of all individual organochlorine insecticides
      in tissue were less than 6 ng/g, wet wt. Concentrations of sigmaPCBs in tissue
      did not exceed 100 ng/g, wet wt. Concentrations of toxic metals were less than
      the limits of detection. Because no significant numbers of green frog deformities
      were observed in this region, it can be assumed that at these low concentrations,
      physical malformations in green frogs should not be observed. Significance of
      study. This study provides information on the incidence of deformities in green
      frog populations in southwestern Michigan and offers background data on chemical
      residues in green frogs and their environment.

PMID- 11459137
TI  - Environmental fate and bioavailability of wood preservatives in freshwater
      sediments near an old sawmill site.
AB  - Impacts of an old contaminated sawmill site located in Eastern Finland were
      studied, with emphasis on transportation and bioaccumulation of wood
      preservatives in the surrounding water system. To assess the transportation of
      chlorophenols and chromated copper arsenate (CCA) from the sawmill to the nearby
      lake, the concentrations of these compounds in selected sediment samples were
      analyzed. To assess the contribution of a pulp mill further upstream, the
      concentration of extractable organic halogens (EOX) was analyzed. Bioaccumulation
      of wood preservatives from sediments was examined using Lumbriculus variegatus as
      test organism. In sediments collected from the sawmill area, concentrations of
      chlorophenols, arsenic, chromium and copper were high. In the surrounding area
      the concentrations of these compounds were slightly elevated at some sampling
      points but were mostly within the natural range of variation. Thus, it can be
      concluded that transportation of wood preservatives from the sawmill area to its
      surroundings is fairly low. However, 60 microg/l of arsenic and 50 microg/l of
      copper were found in water taken from a brook that runs through a landfill area
      of the sawmill to the nearby river, and the concentration of arsenic in the
      surface sediment at one sampling point in the lake was slightly elevated. The
      total amount of organohalogens in sediment was higher in the river and the lake
      than in the sawmill area. Of all the wood preservatives studied, only arsenic was
      found to bioaccumulate in present conditions, reaching a tissue concentration of
      362 microg/g dw in organisms exposed for 28 days to sediment from the brook. High
      concentration of arsenic in oligochaeta tissue was related to high concentration
      of arsenic in the pore water.

PMID- 11459138
TI  - Metals in tissues of European otters (Lutra lutra) from Denmark, Great Britain
      and Ireland.
AB  - Samples of livers of European otters from Denmark, Great Britain and Ireland were
      analyzed for manganese, chromium, zinc, copper, nickel and cobalt. Concentrations
      were generally significantly higher in samples from Great Britain. It was
      considered that this reflected the catchment geology from where the specimens
      originated.

PMID- 11459139
TI  - Glutamate and calcium uptake in astrocytes after acute lead exposure.
AB  - The neurotoxicity of lead is well known, but the exact mechanisms of its toxicity
      are not solved yet. Disturbances in glutamate homeostasis of neural tissue and
      interactions of lead with calcium metabolism have been considered as a potential
      mechanism. In the present study, we evaluate the acute effect of lead exposure by
      studying glutamate uptake, as well as calcium influx and intracellular lead in
      cultured rat cerebellar astrocytes. Glutamate uptake and calcium influx were
      evaluated with radioactive probes by liquid scintillation counting, and
      intracellular lead was measured by atomic absorption method. Lead increased
      calcium influx dose dependently, but in an acute 15-min exposure it had no
      statistically significant effect on glutamate uptake into astrocytes. Calcium
      decreased at high concentrations but did not hamper lead uptake. Lead uptake rate
      into astrocytes was high compared to calcium.

PMID- 11459140
TI  - Toxicity of copper in an oxic stream sediment receiving aquaculture effluent.
AB  - Sediments were collected from a stream (upstream, outfall and downstream)
      receiving copper laden catfish pond effluent to assess toxicity to non-target
      biota. No significant reduction in Hyalella azteca survival or growth (10 d), or
      Typha latifolia germination and root and shoot growth (7 d) were observed after
      exposure to upstream and outfall sediments. A significant reduction in H. azteca
      survival was observed after exposure to the downstream sediment sample; however,
      no reduction in T. latifolia germination or seedling growth was detected. Bulk
      sediment copper concentrations in the upstream, outfall and downstream samples
      were 29, 31, and 25 mg Cu/kg dry weight, respectively. Interstitial water (IW)
      concentrations ranged from 0.053 to 0.14 mg Cu/l with 10 d IW toxicity units > or
      = 0.7. Outfall samples were amended with additional concentrations of copper
      sulfate so that bulk sediment measured concentrations in the amended samples were
      172, 663, 1245, and 1515 mg Cu/kg dry weight. Survival was the most sensitive
      endpoint examined with respect to H. azteca with a no observed effects
      concentration (NOEC) and lowest observed effects concentration (LOEC) of 1245 and
      1515 mg Cu/kg, respectively. NOEC and LOEC for T. latifolia root growth were 663
      and 1245 mg Cu/kg, respectively. IW copper concentrations were > or = 0.86 mg
      Cu/l with H. azteca intersitial water toxicity unit (IWTU) concentrations > or =
      1.2. Sequential extraction qualitatively revealed the carbonate and iron oxide
      fractions which accounted for a majority of the copper binding. In this instance,
      the copper which was applied to catfish ponds does not appear to be adversely
      impacting the receiving stream system.

PMID- 11459141
TI  - Determination of the aquatic PNEC0.05 for boron.
AB  - Several weight of the evidence approaches for the effects assessment of boron to
      aquatic organisms have been conducted. The focal point for all of these
      assessments is the appropriate interpretation of the LC1 for rainbow trout
      (Oncorhynchus mykiss) from W.J. Birge, J.A. Black, Report No. EPA5601176408.
      Environmental Protection Agency, Office of Toxic Substances, Washington, DC,
      1977, as the LC1 from their studies provided the lowest chronic toxicity values
      for boron. Other studies by these investigators (W.J. Birge, J.A. Black,
      Completion Report prepared for the Procter & Gamble Company, Cincinnati, USA,
      1981; W.J. Birge, J.A. Black, A.G. Westermann, T.M. Short, S.B. Taylor, M.C.
      Parekh. Completion Report prepared for the Procter & Gamble Company, Cincinnati,
      USA, 1984; J.A. Black, J.B. Barnum, W.J. Birge, Chemosphere 26 (1993) 1383-1413)
      further indicate this species to be particularly sensitive to boron. While weight
      of the evidence approaches have been necessary for diverse risk assessment needs,
      they each suffer from potential bias via professional judgment. In order to allay
      these issues and to update the effects assessment for boron, a probabilistic
      approach was used. Raw data from the Birge and Black studies were reanalyzed to
      generate chronic values representative of the adverse effects threshold (e.g.,
      LC10) for several species. A comprehensive list of chronic data from these
      studies and other studies were combined into a cumulative probability term,
      allowing for the determination of the fifth percentile protection value, or
      PNEC0.05. The PNEC0.05 for boron was determined to be at least 1.3 mg B/l.

PMID- 11459142
TI  - Blood:air partition coefficients of individual and mixtures of trihalomethanes.
AB  - The objective of the present study was to determine the rat blood:air partition
      coefficients (P(b:a)) of chloroform, bromodichloromethane, dibromochloromethane
      and bromoform present in vitro individually or as mixtures. The experimentally
      determined P(b:a) of chloroform, bromodichloromethane, dibromochloromethane and
      bromoform present individually corresponded to (mean +/- SD, n = 8) 21.3 +/- 1.8,
      41.8 +/- 6.2, 97.5 +/- 4.1, and 187 +/- 7.4, respectively. The P(b:a) of these
      trihalomethanes (THMs) showed a decreasing trend during mixed in vitro exposures
      to 0.138 +/- 0.002 or 0.273 +/- 0.002 micromol of each of the four THMs. In
      general, the P(b:a) determined during mixed exposures differed by < or = 15% of
      the average P(b:a) determined for THMs present individually. The results of this
      study suggest that an alteration of P(b:a) of the individual THMs is unlikely to
      occur at the blood concentrations of THMs observed during mixed exposures in
      rats.

PMID- 11459143
TI  - Application of the comet and micronucleus assays to butterfish (Pholis gunnellus)
      erythrocytes from the Firth of Forth, Scotland.
AB  - This report describes an investigation of genotoxic effects in an inter-tidal
      fish species sampled along a pollution gradient in the Firth of Forth, Scotland,
      UK. The comet assay is an electrophoretic technique for measuring DNA breakage in
      nuclei from individual cells and has only recently been applied to field
      investigations of genotoxicity. The measurement of nuclear anomalies (NA), such
      as the presence of micronuclei (MN) and 'lobes', has been successfully utilised
      in many field studies of genotoxic effects of contaminated sediments. These two
      techniques were applied to nucleated red blood cells (RBC) from the butterfish,
      Pholis gunnellus. The comet assay was adapted and validated for use in this
      species. Fish were sampled from the inner Firth of Forth, which has a legacy of
      industrial contamination and the outer Firth of Forth which is comparatively
      clean. The analysis of DNA strand breakage using this technique did not reveal
      any significant differences between animals sampled from inner and outer zones of
      the Firth. In contrast, MN and NA frequencies were elevated in the inner polluted
      zone of the Firth compared to the outer zone. This study suggests: (1) there are
      genotoxic effects associated with contaminants in the inner Firth of Forth, and
      (2) the comet assay may not be a suitable genotoxicity biomarker in fish.

PMID- 11459144
TI  - A new monoclonal antibody against vitellogenin from rainbow trout (Oncorhynchus
      mykiss).
AB  - Monoclonal antibodies were developed against vitellogenin (vtg) of rainbow trout.
      This protein is used as a biochemical response to the exposure with estrogenic
      compounds. Several mice were immunized with purified vtg and the spleen cells of
      these mice were fused with myeloma cells. The resulting hybridoma cells were
      screened with an enzyme immunoassay for the production of specific anti-vtg
      antibodies. Twelve positive cell lines were detected. The hybridoma cell line
      B8D8 was adjusted to serum free medium; it produced monoclonal antibodies with a
      high selectivity and sensitivity. A detection limit of 5 microg/l vtg was
      achieved with a competitive enzyme immunoassay applying a preincubation step and
      a streptavidin-biotin amplification system (ABC system). Cross-reactivity with
      vtg of other species was detected with roach (Rutilus rutilus), flounder
      (Platichthys flesus) and dab (Limanda limanda). The assay was applied to rainbow
      trout (Oncorhynchus mykiss), which were exposed for six months to defined
      concentrations of effluents (10%, 20%, 30% and 40%) and surface water. Increased
      vtg levels in male fish are correlated with the increasing levels of effluent.
      The effluent levels in the exposure experiments are relevant for effluent
      loadings of the Berlin waterways during the seasons of the year.

PMID- 11459145
TI  - Traditional versus WHIM molecular descriptors in QSAR approaches applied to fish
      toxicity studies.
AB  - Quantitative structure-activity relationships (QSAR) were performed on nine
      congenetic aromatic hydrocarbons. Acute response was evaluated in freshwater fish
      species. QSAR were built by Hansch's approaches and weighted holistic invariant
      molecular (WHIM) indices. The prediction power of QSAR from both approaches was
      evaluated. Single regression analysis derivated by Hansch's approach seem
      suitable for non-polar compounds. However, for all species, it has not a high
      predictive power (Q2(LOO)) of the biological activity from only K(ow) as
      molecular descriptor. Multiple regression analysis obtained from WHIM descriptors
      showed Q2(LOO) higher than 80%, indicating that molecular descriptors have a
      prediction power greater than K(ow).

PMID- 11459146
TI  - Prediction of the Daphnia acute toxicity from heterogeneous data.
AB  - Two descriptors (log(P(ow)), 'hardness') were selected to predict the Daphnia
      acute toxicity of a training set of heterogeneous chemical compounds. The data
      were extracted from 523 notification files about new chemicals stored at the
      French Department of Environment. The selection of the descriptors was carried
      out using a statistical method coupling ordinary least square (OLS) regression
      and genetic algorithm (GA). The validity limits for the final equation are
      discussed by comparing the actual and predicted activities of several compounds.
      The study points out the interest of the 'hardness' parameter for quantitative
      structure-activity relationships (QSAR) with a heterogeneous data set.

PMID- 11459147
TI  - Estimating biotransformation rate constants of organic chemicals from modeled and
      measured elimination rates.
AB  - In this study, biotransformation rate constants are estimated for a large set of
      organic compounds. Biotransformation (km) is considered part of the total
      elimination, further consisting of physico-chemical elimination to water (kw),
      depuration by feces (kf) and growth dilution (gamma). Existing models are used to
      estimate kw and kf, and gamma. The difference between measured elimination rate
      constants and the sum of predicted elimination rate constants for water, feces
      and growth indicates the ration of biotransformation in the total elimination. In
      all examined animal classes, polycyclic aromatic hydrocarbons seem to be
      metabolized at an intermediate rate. Because of the relative low hydrophobicity
      of some of the studied compounds, their physico-chemical elimination rate
      constant is relatively high, and the relative contribution of metabolism to total
      elimination of these compounds is therefore relatively low. Fish seem to be
      capable of metabolizing chlorodibenzo-p-dioxins and -furans, DDT, chloroanilines
      and phenol.

PMID- 11459148
TI  - QSAR study on the toxicity of substituted benzenes to the algae (Scenedesmus
      obliquus).
AB  - 50% effective inhibition concentration 48h-EC50 of 40 substituted benzenes to the
      algae (Scenedesmus obliquus) was determined. The energy of the lowest unoccupied
      molecular orbital (E(LUMO)) was calculated by the quantum chemical method
      MOPAC6.0-AM1. By using E(LUMO) and the hydrophobicity parameter log K(OW) the
      quantitative structure-activity relationship model (QSAR) was developed:
      log1/EC50=0.272 logK(OW) - 0.659E(LUMO) + 2.54, R2 = 0.793, S.E. = 0.316, F =
      71.07, n = 40. A series of equations were obtained about the measured EC50 values
      of different subclasses of compounds. For those compounds containing double -NO2,
      their toxicity may be related chiefly to the intracellular reduction of -NO2
      obtaining electron, while for anilines and phenols, K(OW) contributes most to the
      QSAR and E(LUMO) very little.

PMID- 11459149
TI  - The effects of solar UV-B radiation on embryonic mortality and development in
      three boreal anurans (Rana temporaria, Rana arvalis and Bufo bufo).
AB  - Many species of amphibians have experienced population and range reductions. It
      has been hypothesized that sensitivity to UV-B may contribute to the population
      declines of some amphibian species. We performed field experiments to measure the
      effects of solar UV-B on the hatching success of three Finnish anuran species,
      the common frog (Rana temporaria), moor frog (Rana arvalis) and common toad (Bufo
      bufo). Further, the effects of natural UV-B radiation on survival of the tadpoles
      of the same three species of anurans were tested. A significant percentage of R.
      temporaria and B. bufo embryos survived when exposed to and protected from solar
      UV-B and hatching success was not affected by solar radiation. Elimination of
      solar UV-B significantly increased the hatching success of R. arvalis, but
      embryonic mortality was high in both treatments. The data indicates that under
      natural conditions, solar UV-B radiation influences embryo survival in R.
      arvalis, but has no effect on R. temporaria and B. bufo. Solar UV-B radiation had
      no effect on R. temporaria and R. arvalis tadpoles, but elimination of UV-B
      significantly increased survival of B. bufo tadpoles. It seems that ambient UV
      radiation levels have no effect on R. temporaria but may affect R. arvalis and B.
      bufo at different developmental stages.

PMID- 11459150
TI  - Acute toxicity of substituted phenols to Rana japonica tadpoles and mechanism
      based quantitative structure-activity relationship (QSAR) study.
AB  - Acute 12 h and 24 h lethal toxicity (12 h-LC50 and 24 h-LC50) of 31 substituted
      phenols to Rana japonica tadpoles was determined. Results indicate that toxicity
      of phenols to tadpoles varied only slightly with length of exposure and the 12-h
      test could serve as surrogate of the 24-h test. A mechanism-based quantitative
      structure-activity relationship (QSAR) method was employed and 1-octanol/water
      partition coefficient (log K(ow))-dependent models were developed to study
      different modes of toxic action. Most phenols elicited their response via a polar
      narcotic mechanism and an excellent logK(ow)-dependent model was obtained. Soft
      electrophilicity and pro-electrophilicity were observed for some phenols and a
      good log K(ow)-dependent model was also achieved. Additionally, the significant
      dissociation of carboxyl on benzoic acid derivatives sharply reduced their
      toxicity. A statistically robust QSAR model was developed for all studied
      compounds with the combined application of log K(ow), energy of lowest unoccupied
      orbital (E(lumo)), heat of formation (HOF) and the first-order path molecular
      connectivity dices (1chi(p)).

PMID- 11459151
TI  - Effect of selected pesticides and their ozonation by-products on gap junctional
      intercellular communication using rat liver epithelial cell lines.
AB  - The non-genotoxic effects of two commonly used pesticides, 1,1-bis (p
      chlorophenyl)-2,2,2-trichloroethane (DDT) and malathion, and one widely used
      commercial insect repellent N,N-diethy-m-toluamide (DEET) on gap junction
      intercellular communication (GJIC) were determined using a rat liver epithelial
      cell line. Malathion and DDT reversibly inhibited GJIC in a treatment time- and
      dose-dependent manner at non-cytotoxic doses, whereas, DEET did not inhibit GJIC.
      Malathion was very reactive with ozone, while DEET and DDT did not react to any
      appreciable extent with ozone. The mixtures of ozonation products from malathion
      and DEET did not inhibit GJIC. The mixtures of ozonation by-products formed from
      DDT inhibited GJIC, but to a lesser extent than did DDT, itself. These results
      suggest that ozone can effectively remove malathion from solution without forming
      GJIC-toxic products, but is less effective in eliminating DEET and DDT from
      solution.

PMID- 11459152
TI  - Effects of procymidone, fludioxonil and pyrimethanil on two non-target aquatic
      plants.
AB  - Procymidone, fludioxonil, and pyrimethanil are widely used to control the
      pathogenic fungus Botrytis cinerea in Champagne's vineyards. These fungicides may
      end up in surface waters and present potential risks for aquatic vascular plants
      and algae. Therefore, their toxicity was evaluated on Lemna minor and Scenedesmus
      acutus in six-day or 48-h tests, respectively. Based on growth and chlorophyll
      (Chl) content of L. minor and S. acutus cultures, the results showed that the
      alga was the most sensitive to the fungicides. Among the fungicides, pyrimethanil
      was the most toxic for L. minor, its nominal IC50 was 46.16 mg l(-1) and that of
      the other two was >100 mg l(-1). In contrast, pyrimethanil appeared the least
      toxic for S. acutus at low concentration, nominal IC50 were 22.81, 4.85, and 4.55
      mg l(-1) for pyrimethanil, fludioxonil, and procymidone, respectively. Fate of
      the fungicides in the media was also investigated and acute toxicity of the
      agrochemicals is discussed in regard to concentration in the culture media. Poor
      solubility of procymidone and fludioxonil appeared to be partly responsible for
      the low toxicity of these fungicides. Based on these toxicity data and the
      concentrations found in ponds collecting vineyard runoff water, these pesticides
      should not impair the establishment of pioneer plants.

PMID- 11459153
TI  - Effects of bis(tributyltin)oxide on antipredator behavior in threespine
      stickleback Gasterosteus aculeatus L.
AB  - Antipredator behavior was used as a parameter to detect effects caused by
      exposure to the organotin compound bis(tributyltin)oxide (TBTO). Three groups of
      threespine sticklebacks (Gasterosteus aculeatus L.) were exposed to 3, 9 and 27
      ppb TBTO, respectively. A fourth control group was given the same treatment as
      the other three groups, but no TBTO. Antipredator behavior of the fish was evoked
      using a dummy heron (Ardea cinerea) bill. TBTO exposure caused significant
      changes in the spatial position of the fish in the aquarium (P(Loc)), their
      response to predator attack (P(Res)), recovery time (P(Rec)) and latency time
      (P(Lat)). Some of the effects were, however, reversible after the exposure was
      terminated. We suggest that behavior as an indicator of pollution may be used as
      an ecologically relevant integrative biomarker.

PMID- 11459154
TI  - PCBs, TEQs and plasma retinol in grey heron (Ardea cinerea) hatchlings from two
      rookeries in Norway.
AB  - Fish-eating birds are particularly subject to accumulation of persistent organic
      pollutants, and polychlorinated biphenyls (PCBs) have been shown to constitute a
      major hazard for this group of birds. Grey heron (Ardea cinerea) hatchlings from
      two rookeries were applied as sentinel species to study PCB burdens in coastal
      ecosystems in mid Norway and north Norway, and plasma retinol and dioxin
      equivalencies (sigmaTEQ) were applied to assess toxic effects of the PCB-burdens.
      The results show that grey herons appear to be amongst the fish-eating birds in
      Norway that are accumulating PCBs to the largest extent. There were no
      differences in sigmaPCB or sigmaTEQ in the yolk of grey heron hatchlings from the
      two rookeries and, accordingly, none in plasma retinol concentrations either.
      Furthermore, plasma retinol concentrations could not be related to sigmaPCB or
      sigmaTEQ. Thus, it seems that exposure levels are below the threshold for gross
      retinoid-related effects in grey heron hatchlings. There are also indications
      that the grey heron could be relatively insensitive to retinoid-related effects
      of PCBs. In the hatchlings with the highest pollutant levels, sigmaTEQs were in
      the lower range of levels that have been associated with reduced hatching success
      in other fish-eating bird species.

PMID- 11459155
TI  - Evaluation and refinement of a continuous seed germination and early seedling
      growth test for the use in the ecotoxicological assessment of soils.
AB  - Four higher plant species (Avena sativa L., oat; Lepidium sativum L., cress;
      Brassica rapa Metzg., turnip; and Phaseolus vulgaris L., bush bean) and 15 soils
      including five mineral oil-contaminated soils were tested to assess a soil-based
      continuous seed germination and early seedling growth bioassay. Seed germination
      was recorded and the shoot biomass of 14-day seedlings measured. An automatic
      self-watering system was compared with the daily hand watering. Results obtained
      from this study show that the self-watering system had minor effects on both seed
      germination and early seedling growth, and that soil nutrient status rather than
      soil texture significantly affected both seedling emergence and shoot biomass.
      Proportional dilution of suspicious samples from primary tests with an
      appropriate control soil is recommended for secondary tests. Shoot biomass is a
      more sensitive measurement endpoint than seed germination. Bush bean should not
      be recommended for use due to its low sensitivity to mineral oil and poor
      germination in soil.

PMID- 11459156
TI  - Analysis of the effects of rotational larviciding on aquatic fauna of two Guinean
      rivers: the case of permethrin.
AB  - Within the Onchocerciasis Control Programme about 50,000 km of west African
      rivers have been regularly sprayed with larvicides to control the vector of
      dermal filariasis caused by Onchocerca volvulus. Since the beginning of the
      programme invertebrates and fish data were collected to monitor adverse effects
      on non-target organisms. The regular series of biological and hydrological data
      collected in two Guinean rivers were analysed to evaluate the effects of
      rotational larviciding with particular attention to permethrin, as preliminary
      acute toxicology tests and semi-field experiments suggest it has stronger effects
      on non-target fauna in respect to other larvicides. Invertebrates and fish
      variations in biomass and species richness are seasonal and flow-related and the
      results presented here do not support any evidence of specific effects of
      permethrin application on the biological targets monitored. Larvicide
      applications influence community structures, putting pressure on some taxonomic
      groups, causing, for example, the rarefaction of some taxa. In spite of the above
      results, the scarcity of some invertebrate systematic units does not result in a
      significant reduction of total invertebrate density because of the corresponding
      increase in other systematic units. In nature the studied aquatic communities
      would rarely be in equilibrium because of frequent natural stresses, such as
      drought and spate events, the biological variations discussed are to be
      considered ecologically acceptable.

PMID- 11459157
TI  - Detection of directed gaze in rhesus monkeys (Macaca mulatta).
AB  - To examine the ability of monkeys to detect the direction of attention of other
      individuals, the authors quantitatively investigated the visual scanning pattern
      of rhesus monkeys (Macaca mulatta) in response to visually presented images of a
      human frontal face. The present results demonstrated not only that monkeys
      predominantly gaze at the eyes as compared with other facial areas in terms of
      duration and number of fixations, but also that they gaze at the eyes for a
      longer time period and more frequently when a human face, presented as a
      stimulus, gazed at them than when the gaze was shifted. These results indicate
      that rhesus monkeys are sensitive to the directed gaze of humans, suggesting that
      monkeys pay more attention to the human whose attention is directed to them.

PMID- 11459158
TI  - Comprehension of human communicative signs in pet dogs (Canis familiaris).
AB  - On the basis of a study by D. J. Povinelli, D. T. Bierschwale, and C. G. Cech
      (1999), the performance of family dogs (Canis familiaris) was examined in a 2-way
      food choice task in which 4 types of directional cues were given by the
      experimenter: pointing and gazing, head-nodding ("at target"), head turning above
      the correct container ("above target"), and glancing only ("eyes only"). The
      results showed that the performance of the dogs resembled more closely that of
      the children in D. J. Povinelli et al.'s study, in contrast to the chimpanzees'
      performance in the same study. It seems that dogs, like children, interpret the
      test situation as being a form of communication. The hypothesis is that this
      similarity is attributable to the social experience and acquired social routines
      in dogs because they spend more time in close contact with humans than apes do,
      and as a result dogs are probably more experienced in the recognition of human
      gestures.

PMID- 11459159
TI  - Relative pitch perception in Japanese monkeys (Macaca fuscata).
AB  - To investigate whether monkeys perceive relative pitch, the author trained 3
      Japanese monkeys (Macaca fuscata) to detect changes from rising to falling
      contours of 3-tone sequences. Tone sequences were presented serially with
      transposition, so monkeys were urged to attend to cues other than the absolute
      frequency of a component tone. Results from probe tests with novel sequences
      showed that monkeys discriminated by the relative pitch when the frequency ranges
      of sequences were within the training range, showing a similar tendency as birds
      in previous studies (e.g., S. H. Hulse, J. Cynx, & J. Humpal, 1984).

PMID- 11459160
TI  - Exposure to a rhythmic auditory stimulus facilitates memory formation for the
      passive avoidance task in the day-old chick.
AB  - Previous research regarding the beneficial effects of auditory stimuli on
      learning and memory in humans has been inconsistent. In the current study, day
      old chicks were used to reduce the impact of individual differences on responses.
      Chicks were trained on a passive avoidance task and exposed to various auditory
      stimuli. Exposure to a complex rhythmic sequence for 1 min strongly facilitated
      chicks' long-term memory. The optimal time of presentation of the stimulus was
      between 10 min before and 20 min after training. Moreover, the enhancing effect
      was not generalized to the other auditory stimuli tested. It is suggested that
      this effect may be due to arousal because arousal hormones are critical to long
      term memory formation. This study indicates that the temporal characteristics and
      type of stimulus may be important considerations when investigating the effects
      of auditory stimuli on cognitive functioning.

PMID- 11459161
TI  - What guides a search for food that has disappeared? Experiments on cotton-top
      tamarins (Saguinus oedipus).
AB  - When food is launched down a vertically positioned S-shaped opaque tube, cotton
      top tamarins (Saguinus oedipus) search for the food in the position directly
      beneath the release point, even though over several trials it never appears in
      this position (B. M. Hood et al., 1999). Experiment 1 showed that when the
      trajectory of the food shifts from the vertical to the horizontal plane, tamarins
      no longer show systematic perseverative errors and, in general, perform better on
      this invisible displacement task. Experiment 2 showed that tamarins with
      experience on the horizontal task show less of a bias when tested on the vertical
      task but nonetheless fail overall to solve this invisible displacement problem;
      their performance is substantially worse than it was on the horizontal task.
      Experiment 3 revealed that when the vertically positioned tube is replaced by an
      occluded ramp, tamarins consistently search in the compartment below the release
      point, even though most of the tamarins had experience in Experiments 1 and 2.
      Overall, results indicate that tamarins have a significant gravity bias when
      searching for food that has disappeared along the vertical plane but also have
      more general problems finding food that has moved out of sight.

PMID- 11459162
TI  - Memory of movies by chimpanzees (Pan troglodytes).
AB  - How do animals remember what they see in daily life? The processes involved in
      remembering such visual information may be similar to those used in interpreting
      moving images on a monitor. In Experiment 1, 4 adult chimpanzees (Pan
      troglodytes) were required to discriminate between movies using a movie-to-movie
      matching-to-sample task. All chimpanzees demonstrated the ability to discriminate
      movies from the very 1st session onward. In Experiment 2, the ability to retain a
      movie was investigated through a matching-to-sample task using movie stills. To
      test which characteristics of movies are relevant to memory, the authors compared
      2 conditions. In the continuous condition, the scenes comprising the movie
      progressed gradually, whereas in the discrete condition, the authors introduced a
      sudden change from one scene to another. Chimpanzees showed a recency effect only
      in the discrete condition, suggesting that composition and temporal order of
      scenes were used to remember the movies.

PMID- 11459163
TI  - Object permanence in orangutans (Pongo pygmaeus), chimpanzees (Pan troglodytes),
      and children (Homo sapiens).
AB  - Juvenile and adult orangutans (n = 5; Pongo pygmaeus), chimpanzees (n = 7; Pan
      troglodytes), and 19- and 26-month-old children (n = 24; Homo sapiens) received
      visible and invisible displacements. Three containers were presented forming a
      straight line, and a small box was used to displace a reward under them. Subjects
      received 3 types of displacement: single (the box visited 1 container), double
      adjacent (the box visited 2 contiguous containers), and double nonadjacent (the
      box visited 2 noncontiguous containers). All species performed at comparable
      levels, solving all problems except the invisible nonadjacent displacements.
      Visible displacements were easier than invisible, and single were easier than
      double displacements. In a 2nd experiment, subjects saw the baiting of either 2
      adjacent or 2 nonadjacent containers with no displacements. All species selected
      the empty container more often when the baited containers were nonadjacent than
      when they were adjacent. It is hypothesized that a response bias and inhibition
      problem were responsible for the poor performance in nonadjacent displacements.

PMID- 11459164
TI  - Vocal syntax development in the white-crowned sparrow (Zonotrichia leucophrys).
AB  - Birdsong development exemplifies the interplay between experience and
      predisposition that occurs during behavioral ontogeny. Songbirds must hear song
      models to develop normal song, yet they preferentially learn conspecific song
      when given a choice in the laboratory. To the extent that features guiding this
      selective learning are pre-encoded in the brain, such features should also
      develop in the song of young birds not exposed to them in tutor models. To
      investigate whether song syntax-phrase number and order--is such a feature in the
      white-crowned sparrow (Zonotrichia leucophrys), the authors tutored males of this
      species with separate phrase models. Birds learned and assembled these into songs
      of species-typical sequence, suggesting that syntax is to some degree pre-encoded
      in white-crowned sparrows. Birds also learned heterospecific phrases, confirming
      previous evidence that note phonology is not the primary cue for selective song
      learning in this species.

PMID- 11459165
TI  - Summation and numerousness judgments of sequentially presented sets of items by
      chimpanzees (Pan troglodytes).
AB  - Summation and numerousness judgments by 2 chimpanzees (Pan troglodytes) were
      investigated when 2 quantities of M&Ms were presented sequentially, and the
      quantities were never viewed in their totality. Each M&M was visible only before
      placement in 1 of 2 cups. In Experiment 1, sets of 1 to 9 M&Ms were presented. In
      Experiment 2, the quantities in each cup were presented as 2 smaller sets (e.g.,
      2 + 2 vs. 4 + 1). In Experiment 3, the quantities were presented as 3 smaller
      sets (e.g., 2 + 2 + 3 vs. 3 + 4 + 1). In Experiment 4, an M&M was removed from 1
      set before the chimpanzees' selection. In Experiments 1 and 2, the chimpanzees
      selected the larger quantity on significantly more trials than would be predicted
      by chance. In Experiments 3 and 4, 1 chimpanzee performed at a level
      significantly better than chance. Therefore, chimpanzees mentally represent
      quantity and successfully combine and compare nonvisible, sequentially presented
      sets of items.

PMID- 11459166
TI  - Effects of caloric, protein, and sodium deprivation on the affiliative behavior
      of Norway rats (Rattus norvegicus).
AB  - The tendency of food-deprived, protein-deprived, and sodium-deprived Norway rats
      (Rattus norvegicus) and their respective controls to affiliate with conspecifics
      deprived of either food, protein, or sodium was examined. The authors found that
      (a) independent of internal state, focal rats offered a forced choice between
      protein-deprived and protein-replete target rats spent more time near replete
      than deprived target rats; and (b) both food-deprived and sodium-deprived focal
      rats offered a forced choice between food-deprived and replete target rats spent
      less time near fasted rats than did well-fed and sodium-replete focal rats. The
      data indicate that (a) rats can distinguish both food-deprived and protein
      deprived rats from replete rats and (b) the deprivation states of rats can affect
      their willingness to affiliate with deprived conspecifics.

PMID- 11459167
TI  - Effects of humidity on reproductive behavior in male and female zebra finches
      (Taeniopygia guttata).
AB  - Zebra finches (Taeniopygia guttata) are regarded as opportunistic breeders with
      reproductive behaviors mediated by short-term proximal environmental conditions.
      This article provides experimental evidence for the role of humidity in
      reproductive behaviors. Zebra finches were subjected to experimentally
      manipulated high levels of relative humidity. Males gathered more nest material
      and sang more. Females showed no relationship between humidity and gathering nest
      materials, egg laying, or changes in rates of vocalization.

PMID- 11459168
TI  - Cultural transmission of vocal traditions in cowbirds (Molothrus ater) influences
      courtship patterns and mate preferences.
AB  - In this study, the authors tested the cultural transmission of vocal traditions
      in cowbirds (Molothrus ater). Young cowbirds from a South Dakota (SD) population
      were housed over winter with adults of the SD population or with adults from an
      Indiana (IN) population. Song differences between the original SD and IN adult
      models were acquired by South Dakota culture (SDC) and Indiana culture (INC)
      males, respectively, and were transmitted to a 2nd cultural generation of birds.
      During playback tests of SDC and INC songs, SD females gave more copulatory
      responses to SDC songs. Finally, males with SD-like songs courted SDC females
      preferentially in breeding season tests, whereas males with IN-like songs courted
      INC females preferentially. These results indicate that the transmission of vocal
      traditions plays a fundamental role in the courtship patterns and mating
      decisions of cowbirds.

PMID- 11459169
TI  - CD80 (B7-1) expression on human acute myeloid leukaemic cells cultured with GM
      CSF, IL-3 and IL-6.
AB  - Acute myeloid leukaemia (AML) blasts rarely express the B7 family of co
      stimulatory molecules and do not elicit a clinically significant autologous T
      lymphocyte anti-tumour response. The aim of this study was the in vitro
      modification of AML blasts to an antigen-presenting cell phenotype characterised
      by upregulated expression of the co-stimulatory molecule CD80 (B7-1). Circulating
      AML cells were induced to undergo partial differentiation in culture with the
      cytokines IL-3, IL-6 and GM-CSF; they exhibited variable upregulation of CD80 and
      continued to express MHC class I and II. These cells remained viable to day 20,
      in contrast with normal peripheral blood mononuclear cells (PBMNC), which did not
      survive under the culture conditions. In contrast to unmanipulated blasts,
      cultured leukaemic cells expressed B7-1. Where initial cytogenetic abnormalities
      were present, they were also seen in flow-sorted CD80-expressing cells after
      culture in cytokines, indicating their malignant origin. The immunogenic
      potential of these cultured cells was highlighted by allogeneic and autologous
      mixed lymphocyte reactions, in which both differentiated, but not unmanipulated,
      blasts produced expansion of T-lymphocyte numbers. Autologous cytotoxic T
      lymphocyte (CTL) assays indicated specific killing of B7-1+ leukaemic cells,
      which was greatly enhanced after priming of the T-lymphocytes by B7-1+ blasts
      prior to the CTL assay, then enabling the CTL to lyse both unmanipulated and
      differentiated leukaemic cells.

PMID- 11459170
TI  - Sensitivity of human melanoma cells to adherent leukocytes depends on the ratio
      between them, the activation status of adherent leukocytes and the metastatic
      potential of tumor cells.
AB  - This study examined the interaction of the poorly metastatic human melanoma cell
      line M4Be and the highly metastatic clone 4 derived from M4Be, with respect to
      fresh adherent leukocytes (AL) isolated from 17 different healthy blood donors.
      These AL contained 80% (73%-93%) monocytes, 15% (6%-20%) B lymphocytes and 5% (1%
      8%) T lymphocytes. The survival of these tumor cells against the stress exerted
      by these AL was estimated with a clonogenic assay where isolated tumor cells were
      co-cultured for 14 days in contact with AL and lipopolysaccharide (LPS). For a
      given blood donor, AL either stimulates or inhibits the colony formation of the
      tumor cells (T) depending on the AL/T ratio, the AL activation status and the
      metastatic potential of tumor cells. At low AL/T ratios (< 10/1) in the presence
      of low (8 ng/ml) and trace (8 pg/ml) levels of LPS, hydrogen peroxide (H2O2)
      release is significantly reduced, and tumor cells significantly increase their
      colony formation; the feeder effect of AL is suggested to be due to low
      concentrations of soluble tumor necrosis factor-alpha (TNF-alpha). At high AL/T
      ratios (> 10/1), whatever the characteristics of the blood donor, clone 4 is
      significantly more sensitive than M4Be to AL activated with medium containing low
      (8 ng/ml) or high (1,000 ng/ml) levels of LPS; this killing effect is suggested
      to be due to TNF-alpha, both soluble and membrane-bound, but not to be due to
      release of H2O2. These data suggest that the regulatory role of AL, which remove
      the majority of human melanoma cells and stimulate the colony formation of a
      small fraction of them, is partly due to TNF-alpha.

PMID- 11459171
TI  - Protein-bound polysaccharide K and interleukin-2 regulate different nuclear
      transcription factors in the NKL human natural killer cell line.
AB  - The activation of natural killer cells and induction of cytotoxicity are complex
      processes whose molecular mechanisms have not been clearly elucidated.
      Stimulation of the NKL human NK cell line with interleukin-2 (IL-2) or protein
      bound polysaccharide K (PSK) leads to sustained growth and cytolytic activity in
      comparison to unstimulated NKL cells. However, it is not known whether both
      agents give rise to the same or different intracellular signals. To determine the
      molecular basis for the action of IL-2 and PSK, the binding activity of AP-1,
      CRE, NF-kappaB, PU.1, SP-1, NFAT, STAT1, STAT5/6, GAS/ISRE and IRF-1
      transcription factors was compared in IL-2- and PSK-stimulated NKL cells. Here we
      report that PSK enhanced AP-1 and CRE binding activities, whereas IL-2 increased
      AP-1 and SP-1 and modified GAS/ISRE, IRF-1 and STAT5. Our results indicate that
      IL-2 and PSK regulate different nuclear transcription factors in NKL cells, and
      that the signal transduction pathway used by these inducers is different.

PMID- 11459172
TI  - Simultaneous transduction of B7-1 and IL-2 genes into human melanoma cells to be
      used as vaccine: enhancement of stimulatory activity for autologous and
      allogeneic lymphocytes.
AB  - In order to construct an immunogenic cellular vaccine, we transduced three HLA
      A*0201 human melanoma lines, selected for expression of classes I and II HLA,
      adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100
      and tyrosinase, with both interleukin-2 (IL-2) and B7-1 genes by the use of a
      polycistronic retroviral vector. The lines were selected to share only the HLA
      A*0201 allele to avoid generation of strong alloreactivity in case of their
      multiple in vivo use in HLA-A*0201 + patients. Phenotypic and functional analysis
      of B7-1-IL2 transduced melanoma lines in comparison with B7-1 transduced and/or
      parental untransduced counterparts were then carried out. Tumor cells expressing
      either B7-1 or both genes did not change their original antigenic profile. From a
      functional point of view, expression of both genes in melanoma lines: (1)
      improved the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly
      transduced or untransduced melanoma cells when subthreshold levels of MHC-peptide
      complexes were expressed by melanoma cells; (2) conferred a distinct advantage in
      the ability to stimulate cytotoxicity and interferon-gamma release by autologous
      and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation
      of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA
      A*0201-melanoma patients. Thus, B7-IL2 gene-transduced melanoma lines appear to
      display a high immunogenicity and could be used as vaccine in melanoma patients.

PMID- 11459173
TI  - Perforin and granzyme B induce apoptosis in FasL-resistant colon carcinoma cells.
AB  - Cytotoxic lymphocytes may induce apoptosis in their target cells by the FasL (Fas
      ligand) pathway or the perforin/granzyme B pathway. It has been shown that Fas
      expressing colon carcinoma (CC) cells are resistant to FasL-mediated apoptosis.
      The aims of this study were to determine whether CC cells are also resistant to
      perforin/granzyme B and whether the FasL resistance lies upstream of caspase-3
      activation. The resistance of the Fas-expressing rat CC531s cells to the FasL
      pathway was confirmed by treating them with recombinant human soluble FasL, using
      rat hepatocytes as a positive control. The intracellular delivery of granzyme B
      by sublytic concentrations of perforin, on the other hand, resulted in many
      features of apoptosis (chromatin condensation, nucleus fragmentation, loss of
      microvilli and internucleosomal DNA fragmentation) within 3 h. Since both the
      FasL and perforin/granzyme B pathways converge at caspase-3, we measured caspase
      3 activity to learn whether the FasL resistance was due to failure to activate
      this crucial executioner. Caspase-3 activation occurred in CC531s cells after
      perforin/granzyme B treatment, but not after the addition of recombinant FasL.
      Furthermore, we showed that caspase-3 activity is involved in the execution of
      perforin/granzyme-B-induced apoptosis in CC531 s cells, since the cell-permeable
      caspase-3 inhibitor Z-DEVD-FMK abrogated DNA fragmentation. Together, these
      results suggest that CC cells are sensitive to perforin/granzyme-B-induced
      apoptosis by activating caspase-3 and FasL resistance lies upstream of this
      executioner caspase.

PMID- 11459174
TI  - Role of adhesion molecules in recruitment of Vdelta1 T cells from the peripheral
      blood to the tumor tissue of esophageal cancer patients.
AB  - The mechanism responsible for tissue specific localization of gammadelta T cell
      subsets is not well understood. In order to explain the sequestration of specific
      gammadelta T cell subsets in the peripheral blood and tumor tissue of patients
      with esophageal cancer, we examined the function and expression of adhesion
      molecules on these cells. A hierarchy in the expression of adhesion molecules was
      observed. In vitro activated gammadelta T cells showed dominant expression of LFA
      1 (CD11a), VLA-alpha4 (CD49d), intermediate expression of VLA-alpha5 (CD49e) and
      L-selectin (CD62L), but low expression of CD44v6 and alphaEbeta7 (CD103). It was
      observed that the gammadelta T cells use LFA-1, L-selectin and CD44v6 to bind to
      squamous cell carcinoma (SCC) cells, whereas they adhere to fibroblast cells
      using LFA-1, VLA-alpha4 and VLA-alpha5. Vdelta1 T cell subsets from the
      peripheral blood gammadelta T cells utilize a larger array of adhesion molecules,
      namely LFA-1, VLA-alpha4, VLA-alpha5, L-selectin and alphaEbeta7, to bind to SCC
      cells compared to the restricted usage of LFA-1, L-selectin and CD44v6 by the
      Vdelta2 T cells. Flow cytometric analysis of tumor infiltrating lymphocytes from
      the esophageal tumors confirmed the selective accumulation of Vdelta1+ gammadelta
      T cells in the tumor compartment. It thus appears that adhesion molecules
      expressed on these lymphocytes play an important role in the recruitment and
      retention of Vdelta1 T cells in the tumor milieu.

PMID- 11459175
TI  - A mesothelioma that is sensitive to locally applied IL-2.

PMID- 11459176
TI  - Characterization of a wheat cDNA encoding mitochondrial ribosomal protein L11:
      qualitative and quantitative tissue-specific differences in its expression.
AB  - We have cloned a cDNA for a ribosomal protein of wheat that is similar to the
      bacterial ribosomal protein L11 (RPL11). To determine the subcellular
      localization of the gene product, we fused the whole cDNA sequence to the coding
      sequence for Green Fluorescent Protein, and expressed the fusion product
      transiently in epidermal cells of pea hypocotyls or dayflower leaves. Localized
      fluorescence was detectable in mitochondria, indicating that this nuclear cDNA
      encodes a mitochondrial ribosomal protein L11 (MRPL11). In lower protists,
      mitochondrial RPL11 is encoded by the mitochondrial genome, but higher organisms,
      including animals, fungi and plants, do not have genes for RPL11 in their
      mitochondrial genomes, suggesting that transfer of the genetic information for
      RPL11 from the mitochondrial genome to the nucleus was a very early event in
      evolution. Transcripts of this wheat gene (TaMRPL11) for mitochondrial RPL11 were
      found in all tissues examined, although qualitative and quantitative differences
      in expression were noted. The transcript sizes were different in different plant
      tissues: 1.0 kb in flowers and roots, and 1.5 kb in shoots. Cold stress
      transiently increased the steady-state level of TaMRPL11 mRNA in shoots, but the
      transcription of TaMRPL11 was completely inhibited by cold treatment for longer
      periods. However, the transcript level in flowers decreased gradually on exposure
      to low temperature. On the other hand, the accumulation of TaMRPL11 transcripts
      in roots was not affected by low temperature. These results suggest that the
      expression of MRPL11 in wheat is regulated precisely, in a tissue-specific
      manner.

PMID- 11459178
TI  - A mutation in SPC42, which encodes a component of the spindle pole body, results
      in production of two-spored asci in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, SPC42 is an essential gene, which encodes
      one of the major components of the spindle pole body (SPB). We report on a
      mutation in the SPC42 gene (spc42-102) that results in a sporulation-specific
      defect. Mitotic growth of haploid and diploid spc42-102 strains is normal and
      both exhibit the same growth rates as the isogenic wild-type strains. Many
      diploid spc42-102/spc42-102 cells undergo normal meiotic nuclear divisions,
      producing four haploid nuclei. However, a significant fraction of meiotic spc42
      102/spc42-102 cells contain two immature SPBs and aberrant nuclei that are not
      surrounded by a prospore membrane. Some 40% of the resultant asci contain only
      two spores, while wild-type diploid cells almost always produce four-spored asci.
      Segregation of auxotrophic markers that are tightly linked to the centromere
      reveals that two-spore asci formed from spc42-102/spc42-102 diploid cells
      exclusively contain nonsister haploid spores. Western analysis and measurements
      of the fluorescent signal from an Spc42p-GFP (green fluorescent protein) fusion
      reveal that the mutant strain fails to accumulate Spc42p at meiosis. Thus, our
      results suggest that insufficiency of Spc42p during meiosis results in a pair of
      immature nonsister SPBs that are not enclosed by prospore membrane.

PMID- 11459177
TI  - The maize WD-repeat gene ZmRbAp1 encodes a member of the MSI/RbAp sub-family and
      is differentially expressed during endosperm development.
AB  - Members of the MSI/RbAp sub-family of WD-repeat proteins are widespread in
      eukaryotic organisms and form part of multiprotein complexes that are involved in
      various biological pathways, including chromatin assembly, regulation of gene
      transcription, and cell division. In this study we report the isolation and
      characterization of a cDNA sequence from Zea mays, which encodes an RbAp-like
      protein (ZmRbAp1) that binds acetylated histones H3 and H4 and suppresses
      mutations that have a negative effect on the Ras/cAMP pathway in yeast. The
      ZmRbAp genes form a gene family and are expressed in different tissues of Z. mays
      L. plants. Determination of its expression pattern during maize seed development
      revealed that ZmRbAp transcripts are abundant during the initial stages of
      endosperm formation. In addition, the transcripts are specifically localized in
      shoot apical meristem and leaf primordia of the embryo. A possible role for the
      ZmRbAp genes in early endosperm differentiation and plant development is
      discussed.

PMID- 11459179
TI  - Insertional inactivation of the flaH gene in the archaeon Methanococcus voltae
      results in non-flagellated cells.
AB  - The marine methanogen Methanococcus voltae possesses two transcriptional units
      that encode a total of four flagellins. Immediately downstream of the flagellin
      genes are a number of ORFs, some of which are cotranscribed with the flagellin
      genes. These putative genes have been named flaCDEFGHIJ, although no biochemical
      data has implicated them in flagellar morphogenesis. None of the flaC-J genes has
      homology to any bacterial gene, with the exception of flaI, which shows homology
      to pilT, a gene that encodes a nucleotide binding protein of the type IV pilus
      family. In this study, insertional mutations in flaH of M. voltae were
      identified. The mutants were non-motile and non-flagellated as determined by
      electron microscopy. Southern hybridization experiments confirmed the insertion
      of a mutagenic vector into flaH and indicated that two, tandem, copies of the
      vector were present. It is believed that insertion of the vector into flaH should
      disrupt the transcription of flaIJ due to polar effects. The flaH mutant
      displayed the same pattern of multiple mRNA transcripts, all originating upstream
      of flaB1, as the wild-type cells. Northern hybridization experiments failed to
      detect a flaHIJ transcript in either wild-type or mutant cells. Immunoblotting
      experiments indicated, however, that the mutants produced similar amounts of
      flagellin, FlaD and FlaE to wild-type cells. Flagellin localization experiments
      suggest that the flaH mutant is deficient in flagellin secretion and/or assembly.
      The mutant also displayed similar preflagellin peptidase activity to the wild
      type cells, indicating that none of the genes flaHIJ is likely to be the gene
      that encodes this enzyme, which is required for cleaving the leader peptide from
      the preflagellins prior to their incorporation into the flagellar filament. This
      is the first data indicating that the flaHIJ gene cluster is essential for
      flagellation in methanogens.

PMID- 11459180
TI  - Pim1, a MAP kinase involved in cell wall integrity in Pichia pastoris.
AB  - Mitogen-activated protein kinases (MAPKs) are key enzymes in the signal
      transduction pathways of eukaryotes. We report the isolation of a Pichia pastoris
      gene, PIM1, which encodes the first MAPK to be identified in this yeast. Pim1
      shows the greatest similarity to fungal MAPKs involved in the maintenance of cell
      integrity. Disruption of the PIM1 gene results in an osmoremediable
      thermosensitive phenotype reminiscent of that observed in mutants affected in the
      MAPK Slt2/ Mpk1 of Saccharomyces cerevisiae, which is involved in ensuring cell
      wall integrity. Furthermore, pim1 mutants are hypersensitive to caffeine and cell
      wall-destabilising compounds. Pim1 is phosphorylated at two sites, and thereby
      activated, in response to heat stress, caffeine and agents that alter the fungal
      cell wall, which is consistent with a role in adaptation to these conditions.
      These results support the idea that the MAPK-based mechanisms which regulate cell
      wall integrity are conserved in yeast species. Pim1 is also doubly phosphorylated
      in S. cerevisiae in response to stimuli that activate the cell integrity pathway
      in this yeast. In addition, Pim1 is able to activate the transcription of a
      reporter gene in one-hybrid experiments, as does its S. cerevisiae counterpart,
      Slt2. Interestingly, however, Pim1 does not rescue the mutant phenotype of an
      slt2delta strain. This indicates some functional divergence in MAPK modulation
      and signal transmission by cell integrity pathways and provides a tool that may
      contribute to a better understanding of MAPK signalling.

PMID- 11459181
TI  - Temperature-sensitive mutations in various genes of Escherichia coli K12 can be
      suppressed by the ssrA gene for 10Sa RNA (tmRNA).
AB  - An Escherichia coli strain with a deletion in the ssrA gene that encodes 10Sa RNA
      (tmRNA) was used to screen for temperature-sensitive (ts) mutants whose ts
      phenotypes were suppressible by introduction of the wild-type ssrA gene. Mutants
      in four different genes were isolated. Ts mutants of this type were also obtained
      in a screen for mutations in thyA, the structural gene for thymidylate synthase.
      The ThyA activity in crude extracts prepared from the ts mutants was temperature
      sensitive. The presence of the ssrA gene caused an increase in the total amount
      of the temperature-sensitive enzyme expressed, rather than suppressing the ts
      activity of the enzyme itself. SsrA-DD, a mutant form of 10Sa RNA, suppressed the
      ts phenotype of a thyA mutant, suggesting that degradation of a tagged peptide
      was not required for suppression of the ts phenotype. Considering the fact that
      ssrA-suppressible mutants could be isolated as temperature-sensitive mutants with
      mutations in different genes, it seems evident that trans-translation can occur
      on mRNA that is not lacking its stop codon.

PMID- 11459182
TI  - Characterization of Gac1p, a regulatory subunit of protein phosphatase type I
      involved in glycogen accumulation in Saccharomyces cerevisiae.
AB  - GAC1 and GLC7 encode regulatory and catalytic subunits, respectively, of a type 1
      phosphatase (PP1) in Saccharomyces cerevisiae that controls glycogen synthesis by
      regulating the phosphorylation state of glycogen synthase (Gsy2p). To investigate
      the role of Gac1p in this process, a set of GAC1 deletions were tested for their
      ability to complement a gac1 null mutation and to associate with Glc7p and with
      Gsy2p. The N-terminal 93 amino acids of Gaclp are necessary and sufficient for
      the interaction with Glc7p, whereas a region spanning residues 130-502 is
      required for Gsy2p binding. Both domains are required for full activity in vivo,
      although the Glc7p-binding domain retains some residual activity and can alter
      the phosphorylase a phosphatase activity of Glc7p in vitro. Further mutational
      analysis showed that Val71 and Phe73 of Gaclp are necessary for binding to Glc7p,
      while Asn356 and Tyr357 of Gaclp are necessary for binding to Gsy2p. These
      results suggest that Gac1p targets PPI to its substrate Gsy2p and that Gac1p may
      alter the catalytic activity of PP . Our data also show that overexpression of
      Gac1p affects glucose repression and ion homeostasis, two additional targets of
      GLC7, suggesting that multiple regulatory subunits compete for Glc7p binding in
      vivo.

PMID- 11459183
TI  - Functional analysis of TamA, a coactivator of nitrogen-regulated gene expression
      in Aspergillus nidulans.
AB  - The tam A gene of Aspergillus nidulans encodes a 739-amino acid protein with
      similarity to Uga35p/Dal81p/DurLp of Saccharomyces cerevisiae. It has been
      proposed that TamA functions as a co-activator of AreA, the major nitrogen
      regulatory protein in A. nidulans. Because AreA functions as a transcriptional
      activator under nitrogen-limiting conditions, we investigated whether TamA was
      also present in the nucleus. We found that a GFP-TamA fusion protein was
      predominantly localised to the nucleus in the presence and absence of ammonium,
      and that AreA was not required for this distribution. As the predicted DNA
      binding domain of TamA is not essential for function, we have used a number of
      approaches to further define functionally important regions. We have cloned the
      tamA gene of A. oryzae and compared its functional and sequence characteristics
      with those of A. nidulans tamA and S. cerevisiae UGA35/DAL81/DURL. The
      Aspergillus homologues are highly conserved and functionally interchangeable,
      whereas the S. cerevisiae gene does not complement a tamA mutant when expressed
      in A. nidulans. Uga35p/Dal81p/DurLp was also found to be unable to recruit AreA.
      The sequence changes in a number of tamA mutant alleles were determined, and
      altered versions of TamA were tested for tamA complementation and interaction
      with AreA. Changes in most regions of TamA appeared to destroy its function,
      suggesting that the overall conformation of the protein may be critical for its
      activity.

PMID- 11459184
TI  - Silencing of antibody genes in plants with single-copy transgene inserts as a
      result of gene dosage effects.
AB  - The stability of Fab antibody fragment expression during plant development was
      studied using two homozygous Arabidopsis thaliana lines that contain single
      copies of the transgenes. These lines exhibited expression characteristics that
      are typical for homology-based post-transcriptional gene silencing. Their
      developmental silencing profiles differed markedly, presumably due to the
      influence of the genomic context on the T-DNAs. In both lines, a clear gene
      dosage effect could be observed: in contrast to the homozygous lines, derived
      hemizygous plants accumulated high levels of Fab fragments throughout
      development. Interestingly, silencing also occurred in double-hemizygous plants,
      which resulted from a cross between the two homozygous lines and had two copies
      of each T-DNA at non-allelic positions in their genome. In all cases, down
      regulation of the Fab levels was strictly correlated with methylation of cytosine
      residues in the transcribed regions of the transgenes. Remarkably, this
      methylation was also found in regions in which the transgenes were non-homologous
      regions. Finally, the time point of down-regulation depended on the culture
      conditions and differed for leaves and roots of the same transgenic plant.

PMID- 11459185
TI  - Origin, diversity and evolution of NBS-type disease-resistance gene homologues in
      coffee trees (Coffea L.).
AB  - The majority of plant disease-resistance genes (R-genes) isolated so far encode a
      predicted nucleotide-binding site (NBS) domain. NBS domains related to R-genes
      show a highly conserved backbone of amino acid motifs, which makes it possible to
      isolate resistance gene analogues (RGAs) by PCR with degenerate primers. Multiple
      combinations of primers with low degeneracy, designed from two conserved motifs
      in the NBS regions of R-genes of various plants, were used on genomic DNA from
      coffee trees, an important perennial tropical crop. Nine distinct classes of RGAs
      of the NBS-like type, representing a highly diverse sample, were isolated from
      Coffea arabica and C. canephora species. The analysis of one coffee RGA family
      suggested point mutations as the primary source of diversity. With one exception,
      coffee RGA families appeared to be closely related in sequence to at least one
      cloned R-gene. In addition, deduced amino acid sequences of coffee RGAs were
      identified that showed strong sequence similarity to almost all known non-TIR
      (Toll/Interleukin 1 Receptor)-type R-genes. The high degree of similarity between
      particular coffee RGAs and R-genes isolated from other angiosperm species, such
      as Arabidopsis, tomato and rice, indicates an ancestral relationship and the
      existence of common ancestors. The data obtained from coffee species suggests
      that the evolution of NBS-encoding sequences involves the gradual accumulation of
      mutations and slow rates of divergence within distinct R-gene families, rather
      than being a rapid process. Functional inferences drawn from the suggested
      pattern of evolution of NBS-type R-genes is also discussed.

PMID- 11459186
TI  - Structural and functional characterization of the recR gene of Streptomyces.
AB  - The recR gene product is necessary for homologous recombination and
      recombinational DNA repair in eubacteria. We report the isolation and sequencing
      of the recR gene from Streptomyces coelicolor. It encodes a protein of 198 amino
      acids, with a predicted molecular mass of 22 kDa. The deduced amino acid sequence
      shows significant similarity to that of RecR proteins from other bacteria,
      including Escherichia coli and Bacillus subtilis. Like these, Streptomyces RecR
      contains potential helix-hairpin-helix, zinc finger and ATP-binding motifs, as
      well as the Toprim domain which is present also in topoisomerases of Types IA and
      II, primases and nucleases of the OLD family. The recR genes of Escherichia coli
      and Bacillus subtilis are immediately preceded by a small ORF (orf12 and orf107,
      respectively). An equivalent ORF (orf1) is also found in Streptomyces. S.
      lividans recR mutants, obtained either by insertional inactivation of recR or by
      deletion of the gene together with the preceding ORF, displayed increased
      sensitivity to DNA-damaging agents (such as UV light and methylmethanesulfonate),
      when compared with the wild-type strain. Both mutants could be complemented by
      the wild-type orflrecR genes and also by the recR gene alone. Based on these
      results, orf1 appears to be dispensable for the repair function of Streptomyces
      RecR. In studies of heterologous complementation, the B. subtilis recR region
      (orf107recR) was found to complement the S. lividans deltaorflrecR mutant, but
      the equivalent region from E. coli (orf12recR) could not. However, in the absence
      of orf107, B. subtilis recR was unable to restore the wild-type phenotype to the
      Streptomyces deletion mutant.

PMID- 11459187
TI  - The 5' terminal region of the Schizosaccharomyces pombe mes1 mRNA is crucial for
      its meiosis-specific splicing.
AB  - The mes1+ gene of Schizosaccharomyces pombe is required for the second meiotic
      division. The single 75-nt intron in mes1 is spliced out only in meiotic cells.
      Here we report a cis-acting element which is responsible for meiosis-specific
      splicing. Both 5' and 3' splice sites of the mes1 intron deviate from the
      consensus sequence. Point mutations which altered these sites so that they
      conformed to the consensus, however, did not affect the splicing pattern of mes1.
      Neither replacement of the mes1 intron with the constitutively spliced intron of
      the nda3 gene, nor replacement of the 3' exon with E. coli lacZ changed the
      splicing pattern. In contrast, deletion of the 5' terminal 125 nt from the 5'
      exon derepressed splicing in vegetative cells, implying that this 5' terminal
      sequence, named SRE (mes1 splicing repression element), inhibits splicing of the
      downstream intron. A potential stem-loop structure in the SRE is predicted.
      Disruption of this stem structure by mutation abolished the repression of mes1
      splicing in vegetative cells. Overexpression of the SRE sequence on a multicopy
      plasmid also relieved the repression of splicing of the authentic mes1
      transcripts. These results suggest that as yet unknown trans-acting factors
      inhibit splicing of the mes1 transcript in vegetative cells by interacting with
      the cis-element SRE.

PMID- 11459188
TI  - The RadB protein from Pyrococcus does not complement E. coli recA mutations in
      vivo.
AB  - A previous publication claimed that the radB gene called Pk-REC from Pyrococcus
      furiosus complemented an E. coli recA mutation. We found that a sequencing error
      had led to the test of a mutant form of Pk-REC. The wild-type radB gene from P.
      furiosus cloned in a similar expression vector to the mutant Pk-REC also appeared
      to complement an E. coli recA mutation. However, the cloned P. furiosus gdh
      (glutamate dehydrogenase) gene showed the same activity. We therefore concluded
      that overexpression of any protein can produce an artificial growth inhibition or
      stationary phase in recA mutant cells, which allows cells to recover from UV
      damage due to the action of repair systems that do not require RecA-like
      activity.

PMID- 11459189
TI  - Genetic mapping of the dominant albino locus in rainbow trout (Oncorhynchus
      mykiss).
AB  - Albinism in animals is generally a recessive trait, but in Japan a dominant
      oculocutaneous albino (OCA) mutant strain has been isolated in rainbow trout
      (Oncorhyncus mykiss). After confirming that this trait is not due to a tyrosinase
      gene mutation that causes OCA1 (tyrosinase-negative OCA), we combined the
      amplified fragment length polymorphism (AFLP) technique with bulked segregant
      analysis (BSA) to map the gene involved in dominant oculocutaneous albinism. Four
      AFLP markers tightly linked to the dominant albino locus were identified. One of
      these markers was codominant and we have it converted into a GGAGT-repeat
      microsatellite marker, OmyD-AlbnTUF. Using this pentanucleotide-repeat DNA
      marker, the dominant albino locus has been mapped on linkage group G of a
      reference linkage map of rainbow trout. The markers identified here will
      facilitate cloning of the dominant albino gene in rainbow trout and contribute to
      a better understanding of tyrosinase-negative OCA in animals.

PMID- 11459190
TI  - Analysis of the introgression of Solanum bulbocastanum DNA into potato breeding
      lines.
AB  - Somatic hybrids have been obtained between potato and Solanum bulbocastanum PI
      245310, a Mexican diploid (2n=2x=24) species. Through restriction fragment length
      polymorphism (RFLP) and randomly amplified polymorphic DNA (RAPD) analyses it was
      found that the somatic hybrids contain each chromosome of the diploid parent and
      that the synteny of RFLP markers noted with tomato, potato and S. brevidens is
      largely maintained in S. bulbocastanum. RFLP analyses of BC1 progeny of two
      different hybrids indicated that a substantial number of markers were either lost
      or were heterozygous, in marked contrast with results previously noted with S.
      brevidens. A RAPD map for all 12 chromosomes of S. bulbocastanum was prepared and
      marker transmission was followed in three BC2 populations. Results with
      chromosomes 3, 8 and 10 from these populations are compared.

PMID- 11459191
TI  - Genetic interactions within TFIIIC, the promoter-binding factor of yeast RNA
      polymerase III.
AB  - TFIIIC is a heteromultimeric protein, made of six distinct subunits in
      Saccharomyces cerevisiae, that binds to RNA polymerase III promoters and triggers
      the assembly of the transcription complex. The largest yeast subunit tau138,
      encoded by TFC3, binds to the B-box promoter element. This binding is defective
      in the temperature-sensitive mutant tfc3-G349E; the mutation responsible is
      located in one of two conserved motifs shared with the B-binding component of
      human TFIIIC. Rare dominant gain-of-function mutations that restore growth at
      high temperature were obtained following ultraviolet mutagenesis of tfc3-G349E.
      All of them resulted from single amino acid substitutions that alter the
      structure of TFIIIC. Three were due to reversion or intragenic suppression (TFC3
      K754E and TFC3-L804H) events. Three were identical isolates of TFC6-E330K, a
      previously described mutation of the tau91 subunit. The remaining suppressors
      mapped in TFC4, and resulted in amino acid replacements in the second largest
      subunit of TFIIIC (tau131). With the exception TFC4-E711K, these affect positions
      that are invariant between the S. cerevisiae and Homo sapiens proteins, and are
      localised in conserved tetratricopeptide motifs. These findings demonstrate a
      close functional interaction between the two largest subunits of TFIIIC and
      underscore the importance of the tetratricopeptide motif of tau131.

PMID- 11459192
TI  - Fish retroposons related to the Penelope element of Drosophila virilis define a
      new group of retrotransposable elements.
AB  - Poseidon and Neptune are two ancient lineages of retroposons related to the
      Penelope element from Drosophila virilis. They have been identified in various
      teleost fish species, including the medakafish (Oryzias latipes), and the
      pufferfishes Fugu rubripes and Tetraodon nigroviridis, whose genomes are
      currently being sequenced. Some of these elements are highly reiterated in fish
      genomes. Penelope-related elements were also identified in blood fluke, shrimp,
      sea urchin, cichlid fish and frog, showing that they are widespread in animals.
      Penelope-related retroposons were not detected among sequences from the
      Drosophila melanogaster and human genome projects, suggesting that they have been
      lost from certain animal lineages. A sequence encoding a putative Uri (also
      called GIY-YIG) endonuclease domain was detected downstream from the gene for
      reverse transcriptase. To the best of our knowledge, this type of endonuclease
      sequence has previously been identified in group I introns and in genes for
      prokaryotic excinucleases but not in retrotransposable elements. Penelope-related
      elements are frequently truncated at their 5' ends and can also be flanked by
      long terminal repeat-like structures. Phylogenetic analysis of the reverse
      transcriptase domain failed to assign Penelope-related retroposons to one of the
      major groups of retroelements. Overall, therefore, the evidence strongly suggests
      that these sequences represent a new group of retrotransposable elements.

PMID- 11459193
TI  - Absence of expression from RNA internalised into electroporated mammalian
      mitochondria.
AB  - Transfection of mammalian mitochondria has proved to be notoriously difficult.
      Whilst there have been sporadic reports of import of foreign nucleic acids into
      isolated organelles, these imported nucleic acids have never been demonstrated to
      be functional. Inability to manipulate mitochondrial gene expression has hampered
      our understanding of RNA processing, maturation and translation in mitochondria.
      In an attempt to establish a model system for mt-RNA expression, we have
      electroporated rat liver mitochondria and mitoplasts in the presence of various
      RNA constructs built around the mitochondrial reporter gene mt-luciferase.
      Following electroporation, a fraction of the RNA was shown to be stably
      maintained, mitochondria remained coupled for oxidative phosphorylation and
      intramitochondrial protein synthesis was unaffected. In no case, however, was
      this RNA translated.

PMID- 11459194
TI  - Crypt1, an active Ac-like transposon from the chestnut blight fungus,
      Cryphonectria parasitica.
AB  - A moderately repetitive element was identified previously in the nuclear genome
      of the chestnut blight fungus, Cryphonectria parasitica, and has been used as a
      probe for population studies of the fungus. We report here that the repetitive
      element is a class II transposon of the hAT family of Activator (Ac)-like
      transposable elements. The element, named Crypt1, has a size of 3563 bp,
      including 21-bp terminal inverted repeats. A unique 8-bp direct repeat sequence
      flanking Crypt1 was identified in each of three clones examined. A single large
      ORF with the potential to encode a putative transposase of 946 amino acid
      residues was deduced from the sequence of Crypt1. Based on amino acid sequence
      alignments, Crypt1 is most closely related to other Ac-like transposons of
      filamentous ascomycetes. A single transcript of approximately 3.0 kb was
      identified by Northern hybridization experiments from Crypt1-containing isolates,
      suggesting that Crypt1 is an active element. An isolate containing a single,
      possibly defective, copy of Crypt1 was identified in C. parasitica isolates from
      China; no Crypt1 transcript was identified in this isolate. Transposition of
      Crypt1 was inferred from Southern and inverse PCR analyses of C. parasitica
      isolates maintained in the laboratory, but transposition appears to be a rare
      event.

PMID- 11459195
TI  - Fine genetic mapping and BAC contig development for the citrus tristeza virus
      resistance gene locus in Poncirus trifoliata (Raf.).
AB  - A map-based cloning strategy has been employed to isolate Ctv, a single dominant
      gene from Poncirus trifoliata that confers resistance to citrus tristeza virus
      (CTV), the most important viral pathogen of citrus. Cloning of this gene will
      allow development of commercially acceptable, virus-resistant cultivars. A high
      resolution genetic linkage map of the Ctv locus region was developed using a
      backcross population of 678 individuals. Three DNA markers that were closely
      linked or co-segregated with Ctv were identified and used to screen BAC libraries
      derived from an intergeneric hybrid of Poncirus and Citrus. Through chromosome
      walking and landing, two BAC contigs were developed: one encompassing the Ctv
      region, and the other spanning the allelic susceptibility gene region. The
      resistance gene contig consists of 20 BAC clones and is approximately 550 kb in
      length; the susceptibility gene contig consists of 16 BAC clones and extends
      about 450 kb. The Ctv locus was localized within a genomic region of
      approximately 180 kb by genetic mapping of BAC insert ends. The BAC contigs were
      integrated with the genetic map; variation in the ratio of genetic to physical
      distance was observed in the vicinity of Ctv. Southern hybridization data
      indicated that a few copies of NBS-LRR class sequences are distributed at or
      around the Ctv locus. Efforts are being made to assign the Ctv locus to a smaller
      genomic fragment whose function can be confirmed through genetic complementation
      of a CTV susceptible phenotype. These results indicate that map-based gene
      cloning is feasible in a woody perennial.

PMID- 11459196
TI  - DNA methylation inhibits expression and transposition of the Neurospora Tad
      retrotransposon.
AB  - Tad is a LINE-like retrotransposon of the filamentous fungus Neurospora crassa.
      We have analyzed both expression and transposition of this element using strains
      with a single copy of Tad located in the 5' noncoding sequences of the am
      (glutamate dehydrogenase) gene. Tad in this position has been shown to carry a de
      novo cytosine methylation signal which causes reversible methylation of both Tad
      and am upstream sequences. Here we find that methylation of the Tad sequences
      inhibits both Tad expression and transposition. This inhibition can be relieved
      by the use of 5-azacytidine, a drug which reduces cytosine methylation, or by
      placing the Tad/am sequences in a dim-2 genetic background.

PMID- 11459197
TI  - Antitumoral activity of a sulphur-containing platinum complex with an acidic pH
      optimum.
AB  - Platinum complexes are essential tools for cancer treatment despite their toxic
      side effects. Here we describe a new platinum complex with sulphurs as complexing
      atoms (thioplatin). PURPOSE: To demonstrate that the antitumoral activity of a
      new sulphur-containing platinum compound (thioplatin) depends on a slightly
      acidic pH. METHODS: Platinum uptake by tumour cells and interaction with DNA was
      determined at slightly acidic or alkaline pH. To demonstrate low in vivo toxicity
      the effects of thioplatin on body weight, blood urea nitrogen, white blood cell
      count and the histopathological appearance of small intestines and kidneys were
      evaluated at doses that displayed antitumoral effects against human small-cell
      lung cancer and human colorectal cancer xenotransplants in nude mice. RESULTS:
      The slightly acidic pH optimum of thioplatin was proven by the altered
      electrophoretic mobility of plasmid DNA, quantitation of the platinum content in
      the DNA of tumour cells and cytotoxicity studies. Thioplatin displayed
      antitumoral activity without severe side effects such as weight loss, renal
      ischaemia, destruction of villi in the small intestine or leukopenia as observed
      at comparable doses of cisplatin. Furthermore, probably due to its lipophilic
      nature, thioplatin was taken up readily even by cisplatin-resistant cells. In
      vivo studies with human tumour xenografts in nude mice showed a therapeutic index
      of thioplatin five to ten times higher than that of cisplatin.

PMID- 11459198
TI  - The effect of atovaquone on etoposide pharmacokinetics in children with acute
      lymphoblastic leukemia.
AB  - PURPOSE: The use of trimethoprim/sulfamethoxazole in the prevention of
      Pneumocystis carinii pneumonia in patients with acute lymphoblastic leukemia
      (ALL) may cause undesirable adverse effects: fungal overgrowth, neutropenia, and
      drug resistance. A possible alternative is atovaquone, a hydroxynaphthoquinone
      with anti-Pneumocystis carinii activity. However, it is not known if atovaquone
      alters the disposition or adverse effects of antileukemic drugs. METHODS: Using a
      crossover study design, we compared the pharmacokinetics of etoposide and its
      CYP3A4-formed catechol metabolite when given as a 300 mg/m2 i.v. infusion
      following daily atovaquone versus trimethoprim/sulfamethoxazole in nine patients.
      RESULTS: The area under the concentration time curve (AUC) of etoposide,
      etoposide catechol and the catechol to etoposide AUC ratio were slightly higher
      (a median of 8.6%, 28.4%, and 25.9%) following atovaquone as compared to
      trimethoprim/sulfamethoxazole (P=0.055, P= 0.031 and P=0.023), respectively. In
      vitro analysis in human liver microsomes showed modest inhibition of etoposide
      catechol formation in the presence of atovaquone. Using uptake of 3H-vinblastine
      in L-MDR1 cells, atovaquone was shown to inhibit P-glycoprotein with an apparent
      Ki of 95.6 microM. CONCLUSIONS: Although the effect of atovaquone on etoposide
      disposition was modest, in light of the fact that the risk of etoposide-related
      secondary acute myeloid leukemia has been linked to minor changes in schedule and
      concurrent therapy, we suggest caution with the simultaneous administration of
      atovaquone and etoposide, particularly if used with other CYP3A4/P-glycoprotein
      substrates.

PMID- 11459199
TI  - Sensitivity to topoisomerase I inhibitors and cisplatin is associated with
      epidermal growth factor receptor expression in human cervical squamous carcinoma
      ME180 sublines.
AB  - The relationship between expression and function of the epidermal growth factor
      (EGF) family of receptors and chemosensitivity remains controversial. We studied
      the chemosensitivity to various anticancer agents of human cervical squamous
      carcinoma ME180 cells, and two resistant subclones, ME180/TNF and ME180/Pt, which
      also differ in their EGF receptor (EGFR) expression. Compared with ME180 cells,
      EGFR is overexpressed sixfold in ME180/TNF cells and is barely detectable in ME
      180/Pt cells. Cell cycle analysis by flow cytometry and BrdU incorporation into
      DNA showed a correlation between EGFR expression and percentage of cells in S
      phase and active DNA replication (35% in high EGFR-expressing ME180/TNF cells,
      19% in non-EGFR-expressing ME180/Pt cells and 23% in parental, intermediate-level
      EGFR-expressing ME 180 cells). By MTT assay and compared with parental,
      intermediate-level EGFR-expressing ME180 cells, high EGFR-expressing ME180/TNF
      cells had a three- to fourfold increased sensitivity to cisplatin, camptothecin
      (CPT), and topotecan, and low EGFR-expressing ME180/Pt cells had a five- to
      ninefold reduced sensitivity to the same agents. In contrast, the degree of cross
      resistance with the topoisomerase II inhibitors doxorubicin and etoposide was
      minimal and the pattern of sensitivity to the anti-microtubulin agents
      vinblastine and paclitaxel was different, with a two- to fourfold decreased
      sensitivity in the high EGFR-expressing ME180/TNF cells and only a 1.5-fold
      decreased sensitivity in the low EGFR-expressing ME180/Pt cells. Neither
      alterations in intracellular CPT levels nor changes in topoisomerase I expression
      or activity, measured as ability to form DNA-protein complexes, were found to
      explain the differences in sensitivity to CPT among the three cell lines. Co
      treatment with CP358774, a specific EGFR tyrosine kinase inhibitor, reduced the
      enhanced sensitivity of high EGFR-expressing ME180/TNF cells to the values
      observed in intermediate EGFR-expressing ME180 cells, but only reduced modestly
      the sensitivity of intermediate expressing ME180 cells. As a result, the
      resistance index of low EGFR-expressing ME180/Pt cells compared with intermediate
      EGFR-expressing ME180 cells was reduced only from five- to fourfold for cisplatin
      and from seven- to fourfold for CPT when ME180 cells were exposed to CP358774.
      CP358774 did not affect the sensitivity to either agent in low EGFR-expressing
      ME180/Pt cells. These results provide evidence that changes in EGFR expression or
      function may play a role in determining chemosensitivity to platinum and
      topoisomerase I poisons in some human tumor systems, and that the EGFR-related
      changes in chemosensitivity may vary depending on the level of EGFR expression
      and/or function.

PMID- 11459200
TI  - Arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and 
      resistant gynecological cancer cell lines.
AB  - PURPOSE: Arsenic compounds have been found to be effective in the treatment of
      acute promyelocytic leukemia through the downregulation of bcl-2 expression.
      Resistant ovarian cancer cells often overexpress bcl-2 or p53 proteins or both.
      We hypothesized that arsenic compounds, such as As2O3 and As2S3, could also be
      active against gynecological cancers resistant to conventional chemotherapy.
      METHODS: We investigated the effects of these two arsenic compounds in vitro on
      ovarian cancer cell lines sensitive (OVCAR, GG, JAM) and resistant (CI80-13S) to
      cisplatin (CDDP) and on human cervical cancer cell lines (HeLa) in comparison
      with their effects on human fibroblasts (HF). A fluorometric assay based on
      measurements of fluorescein diacetate (FDA) in cells was used to determine cell
      viability. Apoptosis was assessed in terms of cell morphology, by flow cytometry
      and by a DNA fragmentation assay. RESULTS: Treatment of each cell line with the
      As2O3 or As2S3 led to a marked dose-dependent decrease in cell growth. The IC50
      of the two compounds indicated a significantly greater cytotoxic effect against
      all the cancer cells tested than against the normal HF. At a clinically
      achievable concentration (2 microM), As2O3 selectively inhibited the growth and
      induced apoptosis in CI80-13S, OVCAR and HeLa cells but had no significant
      apoptotic effect on GG or JAM cells or HF. Following treatment with 5 microM
      As2S3, the CI80-13S, OVCAR and HeLa cells also exhibited growth inhibition and
      induction of apoptosis. CONCLUSIONS: Arsenic compounds (As2O3 and As2S3) can
      inhibit growth and induce apoptosis in human ovarian and cervical cancer cells at
      clinically achievable concentrations, indicating that As2O3 and As2S3 could be
      effective in the treatment of gynecological cancer.

PMID- 11459201
TI  - Effects of the serotonin receptor antagonist cyproheptadine on the activity and
      pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid (DMXAA).
AB  - BACKGROUND: DMXAA (5,6-dimethylxanthenone-4-acetic acid) is a new drug
      synthesized in this laboratory and currently in phase I clinical trial. In mice
      it acts as an antivascular drug, selectively inhibiting tumour blood flow and
      inducing tumour haemorrhagic necrosis with resultant tumour regression. It also
      induces the synthesis of tumour necrosis factor (TNF), nitric oxide and
      serotonin. Cyproheptadine, a type 2 serotonin receptor antagonist, is known to
      reduce the degree of tumour necrosis-induced TNF in mice. We investigated the
      pharmacological interaction between a suboptimal dose of DMXAA (20 mg/kg) and
      cyproheptadine (20 mg/ kg) using mice with Colon 38 tumours that are sensitive to
      DMXAA. METHODS: Mice with or without tumours were treated with DMXAA and/or
      cyproheptadine. Concentrations of plasma and tissue DMXAA and the serotonin
      metabolite 5-hydroxyindoleacetic acid were measured by high performance liquid
      chromatography. TNF concentrations were measured by ELISA. RESULTS: While DMXAA
      alone (20 mg/kg) showed little or no antitumour activity, coadministration with
      cyproheptadine was curative in four of five mice. DMXAA half-lives in plasma and
      tumour tissue were increased 5.1- and 5.6-fold, respectively, and the appearance
      of DMXAA glucuronides in bile was almost completely inhibited for up to 4 h.
      Serum TNF was low and unchanged by cyproheptadine, and plasma concentrations of
      the serotonin metabolite 5-hydroxyindoleacetic acid were also not substantially
      changed. CONCLUSION: The augmentation by cyproheptadine of the induction of
      tumour response to DMXAA reflects a pharmacological interaction, leading to
      increased plasma and tumour half-lives, and to reduced excretion. However, serum
      TNF concentrations were not increased, suggesting that the increased anti-tumour
      effects are mediated by an increased local tumour response, arising from the
      extended tumour DMXAA concentrations.

PMID- 11459202
TI  - In vitro and in vivo antitumor activity of the novel trinuclear platinum complex
      BBR 3464 in neuroblastoma.
AB  - PURPOSE: BBR 3464 is a promising new trinuclear platinum complex that has been
      shown to circumvent the resistance to cisplatin in a panel of tumor cell lines
      and xenografts with acquired or intrinsic resistance to cisplatin. The in vitro
      and in vivo antitumor activity of BBR 3464 was evaluated and compared with that
      of cisplatin in neuroblastoma. METHODS: In in vitro studies, the short- and long
      term cytotoxicities, cell cycle perturbations, the ability to induce apoptosis,
      the intracellular platinum accumulation and DNA platination were evaluated in
      three neuroblastoma cell lines exposed to appropriate drug concentrations for 1
      h. In in vivo studies, BBR 3464 was administered i.v. at doses of 0.30 and 0.35
      mg/kg three times at intervals of 4 days (q4dx3), and cisplatin was administered
      i.v. according to two different schedules (at 2 and 4 mg/kg three times at
      intervals of 4 days and at 6 and 12 mg/kg as single doses). RESULTS: In a short
      term growth inhibition assay, BBR 3464 was shown to be up to 100-fold more potent
      than cisplatin and it was even more potent in a clonogenic assay. The difference
      in the antitumor effect of BBR 3464 on the different cell lines was evident in
      both assays, while cisplatin exerted a comparable antitumor activity in all lines
      tested. Cell cycle analysis demonstrated a longer-lasting block in G2/M phase
      induced by BBR 3464 without the early S phase accumulation induced by cisplatin.
      The higher potency of BBR 3464 appeared to be unrelated to the induction of
      apoptosis, that was lower or at most comparable to cisplatin. Cellular platinum
      accumulation and platinum-DNA adduct formation following BBR 3464 exposure was
      higher than following cisplatin exposure. These differences may have resulted
      from a different mechanism of action and may explain the lack of cross-resistance
      with cisplatin. In xenografts of neuroblastoma, BBR 3464 was confirmed to be very
      potent as compared to cisplatin (MTD 0.35 mg/kg and 4 mg/kg for BBR 3464 and
      cisplatin, respectively). The efficacy of BBR 3464 was superior to that of
      cisplatin when both drugs were administered on a fractionated schedule (q4dx3),
      while BBR 3464 appeared equally active to 12 mg/kg cisplatin administered as a
      single dose. CONCLUSIONS: Our findings indicate that BBR 3464 has a definite
      antitumor effect in neuroblastoma lines and may be a candidate for early clinical
      trials in children with neuroblastoma.

PMID- 11459203
TI  - In vivo inhibition of human CYP1A2 activity by oltipraz.
AB  - PURPOSE: Oltipraz is currently undergoing clinical evaluation as a cancer
      chemopreventive agent, especially with respect to aflatoxin-associated
      hepatocarcinogenesis. The agent's ability to induce phase II xenobiotic enzymes
      that detoxify the ultimate carcinogen formed in vivo is thought to be an
      important mechanism by which disease risk may be attenuated. However, an
      additional mechanism could be a reduction in the activation of environmental
      procarcinogens by certain cytochrome P450 (CYP) isoforms. This hypothesis was
      tested with respect to CYP1A2, by using the clearance of caffeine by N
      demethylation as a phenotypic trait measurement of the isoform's catalytic
      activity. METHODS: Subjects received a single oral dose of caffeine (200 mg) on
      five separate occasions: on the day prior to oltipraz administration (day 0), 2 h
      after the first (day 1) of eight daily oral doses of oltipraz (125 mg) and 2 h
      after the last dose (day 8). In addition, CYP1A2 activity was also measured 2 and
      14 days (days 10 and 22, respectively) after discontinuation of oltipraz
      administration. Plasma concentrations of caffeine and its N-demethylated
      metabolite, paraxanthine, over 24 h after drug administration, were determined by
      HPLC. RESULTS: A single 125-mg dose of oltipraz markedly reduced CYP1A2 activity
      by 75 +/- 13% in nine healthy subjects, resulting in a higher caffeine plasma
      level and prolongation of the in vivo probe's elimination half-life. Daily
      administration of 125 mg oltipraz for 8 days resulted in further inhibition so
      that only 19 +/- 13% of the original baseline level of activity was present.
      However, 2 days after discontinuation of oltipraz treatment, CYP1A2 activity had
      returned to 66 +/- 33% of its original level and complete recovery was achieved
      within 14 days of the chemopreventive agent being stopped. CONCLUSIONS: These
      results demonstrate that oltipraz is a potent, in vivo inhibitor of CYP1A2 in
      humans and, because this isoform is importantly involved in procarcinogen
      activation, they also indicate that such inhibition probably contributes to
      oltipraz's cancer-chemopreventive effect. In addition, the findings also suggest
      the likelihood of significant drug interactions between oltipraz and drugs whose
      metabolism is mediated by CYP1A2.

PMID- 11459204
TI  - DA-125, a novel anthracycline derivative showing high-affinity DNA binding and
      topoisomerase II inhibitory activities, exerts cytotoxicity via c-Jun N-terminal
      kinase pathway.
AB  - PURPOSE: DA-125 [(8S,10S)-8-(3-Aminopropanoyloxyacetyl)-10-[(2,6-dideoxy-2-fluoro
      alpha-L-talopyranosyl) oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12
      naphthacene-dione hydrochloride] is a novel anthracycline derivative with
      anticancer activity. In the present study, we compared the cytotoxicity of DA-125
      with that of doxorubicin in H4IIE rat hepatoma cells and investigated the
      mechanistic basis. Because activation of MAP kinases, in particular c-Jun N
      terminal kinase (JNK), is implicated in apoptotic cell death, the signaling
      pathways responsible for DA-125-induced apoptosis were studied. METHODS:
      Cytotoxicity and apoptosis were measured in H4IIE cells and cells were stably
      transfected with a dominant-negative mutant of JNK1 (JNK1-) by MTT and TUNEL
      assays. Inhibition of topoisomerase II activity was determined in vitro. Drug
      accumulation and DNA binding affinity were determined by fluorescence
      spectroscopy. RESULTS: The cytotoxicity of DA-125 was greater than that of
      doxorubicin (IC50 11.5 vs 70 microM). DA-125 induced apoptosis with 30-fold
      greater potency than doxorubicin. Inhibition of topoisomerase II by DA-125 was
      fourfold greater. The presence of excess beta-alanine, a DA-125 moiety, failed to
      alter cytotoxicity and accumulation of DA-125, indicating that the improved
      cytotoxicity of DA-125 did not result from the beta-alanine moiety. Greater
      cellular accumulation of DA-125 correlated with its high-affinity DNA binding.
      Although neither PD98059 nor SB203580 altered the degree of cytotoxicity induced
      by DA-125, JNK1 cells exhibited about a twofold greater viability than control
      cells. DA-125-induced apoptosis was also decreased in JNK1- -transfected cells.
      CONCLUSIONS: DA-125 potently inhibited topoisomerase II activity and induced
      apoptosis by a high rate of prooxidant production. DA-125 exhibited high-affinity
      DNA binding with improved cellular drug accumulation. Apoptosis induced by DA-125
      involved the pathway of JNK1, but not ERK1/2 or p38 kinase.

PMID- 11459205
TI  - Clinical trial with escalating doses of the antiepidermal growth factor receptor
      humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell
      carcinoma of the larynx and hypopharynx.
AB  - In this open uncontrolled phase I study, nine patients with stage III and IV
      squamous cell carcinoma of the head and neck (SCCHN) were treated with five
      administrations of the humanized antiepidermal growth factor receptor monoclonal
      antibody EMD 72000 in three consecutive ascending dose groups. Loading doses of
      100 mg (group I), 200 mg (group II), and 400 mg (group III) were followed by four
      weekly maintenance doses of half the loading doses, i.e. 50, 100, and 200 mg,
      respectively. Two EMD 72000 administrations were scheduled before and three after
      surgery. The objectives of this trial were (a) to investigate the safety and
      toxicity of multiple EMD 72000 doses, (b) to determine the cumulative maximum
      tolerated dose of EMD 72000 at dosages between 300 mg and 1,200 mg, and (c) to
      determine the serum pharmacokinetics of EMD 72000. In total, 102 adverse events
      (AEs) were reported: five of toxicity grade 3, 18 of toxicity grade 2, 66 of
      toxicity grade 1, and 38 of toxicity grade 0. All AEs of toxicity grade 3 were
      considered to be not or remotely related to EMD 72000. The most frequent study
      drug-related AEs were fever and a transient elevation of liver enzymes. In all
      patients, the time to reach peak serum concentrations (tmax) was within 1-3 h of
      the start of each EMD 72000 infusion. Average peak serum concentrations (Cmax)
      after correction for dosage appeared to be dose-independent, whereas the half
      life (t1/2) showed dose dependency. In conclusion, EMD 72000 was very well
      tolerated in patients with advanced stage SCCHN. The pharmacokinetic data from
      this trial suggest the feasibility of conducting future studies with weekly doses
      of 200 mg EMD 72000.

PMID- 11459206
TI  - Phase I and pharmacokinetic study of LY309887: a specific inhibitor of purine
      biosynthesis.
AB  - PURPOSE: In this phase I trial in humans the safety and pharmacology of LY309887
      on a weekly schedule combined with daily oral 5-mg doses of folic acid were
      evaluated. BACKGROUND: LY309887 is an inhibitor of folate-dependent enzymes
      involved in de novo purine biosynthesis and has a broad preclinical antitumor
      activity. In murine systems, combining this agent with exogenous folic acid
      results in an enhanced therapeutic index. METHODS: This study was a single
      institution, open-label, clinical trial of dose escalation with toxicity and
      pharmacokinetic parameters determined. The dose range studied was 0.5-4 mg/m2 per
      week x6 and then a modified schedule weekly x3 every 6 weeks. RESULTS: Dose
      limiting toxicities were of delayed onset and associated with hematologic,
      neurologic, and mucosal effects. Pharmacokinetic parameters revealed dose
      linearity for AUC and Cmax. Low circulating levels of drug persisted for over 200
      h. Urinary excretion accounted for approximately 50% of the parent drug but was
      highly variable. The urinary excretion was near maximal within 24 h of dosing.
      CONCLUSIONS: The modified dosing schedule allowed repetitive dosing in patients.
      Further evaluation of the 2 mg/m2 per week x3 every 6 weeks with daily oral
      folate supplement as a potential phase II dose may be warranted.

PMID- 11459207
TI  - Phase I-II study of escalating doses of amifostine combined with high-dose
      cyclophosphamide.
AB  - PURPOSE: To evaluate the feasibility and clinical effects of increasing doses of
      amifostine administered four times in 1 day with high-dose (HD) cyclophosphamide
      (CTX). METHODS: A group of 16 patients with a diagnosis of lymphoma were treated
      with HD-CTX given at a total dose of 7 g/m2 subdivided into four doses, each
      preceded by increasing doses of amifostine. A group of 12 lymphoma patients
      previously treated with the same HD-CTX regimen was used as historical controls.
      RESULTS: The dose of amifostine was escalated in cohorts of three patients each
      from 4x570 mg/m2 to 4x910 mg/m2 without severe toxic effects. Further patients
      were treated at the highest dose level. Side effects included a fall in blood
      pressure (always less than 20% of baseline value), asymptomatic hypocalcemia
      (from a median value of 2.4 to 1.7 mmol/l) and a decrease in creatinine clearance
      (from a median value of 102 to 85 ml/min). The parameters of hematotoxicity for
      patients treated in the study were not significantly different from those of the
      historical control patients. CONCLUSIONS: Amifostine can be given safely at a
      dose of 910 mg/m2 four times in 1 day in combination with HD-CTX. With this
      schedule amifostine did not show a myeloprotective effect.

PMID- 11459208
TI  - Successful rescue with leucovorin and thymidine in a patient with high-dose
      methotrexate induced acute renal failure.
AB  - A 54-year-old patient with primary cerebral lymphoma was treated with two 4
      weekly cycles of high-dose intravenous cytarabine (12 g/m2) and methotrexate (3
      g/m2). The administration of the first course proceeded without notable
      complications. Before the administration of methotrexate in the second cycle
      blood cell counts and chemistry showed no abnormalities except for slightly
      increased alkaline phosphatase and gamma-glutamyl-transpeptidase levels which was
      attributed to diphantoin comedication. The patient developed symptoms of acute
      renal failure 7 h after methotrexate infusion which resulted in a very high serum
      methotrexate level (39.84 micromol/l) at 20 h after infusion. Rescue therapy was
      intensified: the leucovorin dosage was increased (1,200 mg continuous i.v.
      infusion every 24 h) and combined with thymidine rescue therapy (8 g/m2 per day
      continuous i.v. infusion every 24 h). Urine alkalinization was increased and
      diphantoin therapy was stopped. Leucovorin eye drops and mouth washes were
      started 5 days after methotrexate administration to prevent conjunctivitis and
      mucositis as a result of high methotrexate levels (>2.4 micromol/l). In spite of
      the fact that serum methotrexate levels remained persistently higher than 0.1
      micromol/l for 12 days, the patient experienced no further short-term systemic
      toxicity except for anaemia (grade 3 according to NCI Common Toxicity Criteria).
      After day 12 intensified rescue therapy and the frequency of alkalinization were
      decreased to standard procedures and stopped on day 19. It is concluded that i.v.
      administration with high-dose methotrexate can result in unpredictable acute
      toxicity. In our patient, acute methotrexate toxicity was treated successfully by
      intensification of classical leucovorin rescue therapy in combination with
      thymidine infusion. In addition, leucovorin mouth washes and eye drops may have
      prevented mucositis and conjunctivitis, respectively.

PMID- 11459209
TI  - A difference between the rat and mouse in the pharmacokinetic interaction of 5,6
      dimethylxanthenone-4-acetic acid with thalidomide.
AB  - PURPOSE: Coadministration of thalidomide, cyproheptadine or diclofenac has been
      shown to increase the area under the plasma concentration-time curve (AUC) of the
      novel antitumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in mice. The
      aim of this study was to further investigate these pharmacokinetic DMXAA-drug
      interactions in the rat model. METHODS: The effects of coadministration of L
      thalidomide, cyproheptadine or diclofenac on the pharmacokinetics of DMXAA were
      investigated in male Wistar Kyoto rats. The effects of L-thalidomide,
      cyproheptadine and diclofenac on microsomal metabolism and plasma protein binding
      of DMXAA were also investigated. RESULTS: No significant alteration in the plasma
      concentration profile for DMXAA was observed following L-thalidomide pretreatment
      in rats. In contrast, when combined with diclofenac or cyproheptadine, the plasma
      AUC of DMXAA was significantly (P<0.05) increased by 48% and 88% and the T1/2 by
      36% and 107%, respectively, compared to controls. Both diclofenac and
      cyproheptadine at 500 microM caused a significant inhibition of DMXAA metabolism
      in rat liver microsomes. In contrast, L-thalidomide had no or little inhibitory
      effect on DMXAA metabolism in rat liver microsomes except for causing a 32%
      decrease in 6methylhydroxylation at 500 microM. None of the drugs had a
      significant effect on the plasma protein binding of DMXAA in the rat. CONCLUSION:
      These studies showed that coadministration of L-thalidomide did not alter the
      plasma DMXAA AUC in rats, in contrast to previous studies in mice, whereas
      diclofenac and cyproheptadine significantly reduced the plasma clearance of DMXAA
      in rats in a similar manner to their effect in mice. The cause of the species
      difference in the pharmacokinetic response to thalidomide by DMXAA is unknown,
      and indicates difficulties in predicting the outcome of such a combination in
      patients.

PMID- 11459210
TI  - Clinical overview of hypertension and emerging treatment considerations.
AB  - Managing hypertension is a complex undertaking, where even the definition of the
      disorder is subject to discussion. Recently, there has been controversy
      concerning the most appropriate measure to determine health risks associated with
      hypertension. In the past, diastolic blood pressure (DBP) was the prime measure
      for defining hypertension, but currently systolic blood pressure (SBP) and pulse
      pressure have gained favor. Evidence now suggests that all three measures should
      be considered as part of the hypertensive profile, with the patient's age
      determining the relative importance of each. Aggressive treatment of hypertension
      may reduce morbidity and mortality. Data from trials clearly indicate that, for
      all stages of hypertension, the goal should be a maximum SBP of <150 mm Hg and a
      DBP of <90 mm Hg, with DBP values as low as 70 mm Hg being safe. For individuals
      with diabetes mellitus, these target values should be even lower--SBP <140 mm Hg
      and DBP <80 mm Hg. As a significant number of deaths attributable to hypertension
      occur in patients who are not diagnosed as hypertensive but whose blood pressure
      (BP) is above the optimal level of 120/80 mm Hg, lowering BP levels in this group
      is recommended as well, with lifestyle modification being first-line therapy.
      Because controlling BP to <140/90 mm Hg often requires the use of two or three
      agents, the tolerability of the entire regimen must be considered. However, with
      the multitude of antihypertensive drugs currently available, no patient's BP
      should remain above the 150/90 mm Hg level.

PMID- 11459211
TI  - Issues in hypertension: drug tolerability and special populations.
AB  - Improvements in the death rate from coronary heart disease and in the control of
      hypertension have leveled off in recent years, reversing a trend toward steady
      improvement that began in 1972. Of the roughly 20% of Americans who suffer from
      hypertension, only 29% achieve adequate control (<140/90 mm Hg) with treatment
      and nearly half receive no treatment at all. Poor adherence to therapy doubtless
      plays a key role in this failure. As a major cause of poor adherence,
      tolerability becomes an extremely important element in any discussion of
      effective antihypertensive treatment. Despite their efficacy in treating
      hypertension, diuretics, beta-blockers, and calcium channel blockers have all
      been associated with numerous side effects, including increased serum lipid
      levels, insulin resistance, and edema. With the introduction of the angiotensin
      converting enzyme (ACE) inhibitors, patients were able to achieve blood pressure
      goals with fewer side effects. These agents, however, cause an irritating cough
      in up to 19% of patients. A newer class of drugs, the angiotensin receptor
      blockers (ARB), have similar effects to the ACE inhibitors, but their highly
      selective nature produces even fewer side effects. Eprosartan is a structurally
      unique ARB. Like the other ARB, this promising new agent has a side effect
      profile similar to placebo, and its response rate rivals or exceeds that of
      enalapril. Although it remains to be seen whether the ARB can significantly
      reduce morbidity and mortality from cardiovascular disease, preliminary data from
      the Evaluation of Losartan in the Elderly (ELITE) trial appear to be promising.

PMID- 11459212
TI  - Renal implications of angiotensin receptor blockers.
AB  - The role of the renin-angiotensin system (RAS) in the regulation of blood
      pressure and the pathogenesis of both hypertension and renal complications
      involves an intricate interplay of genetic and environmental factors. In the case
      of diabetic nephropathy, the genes governing the RAS are an obvious choice in the
      search for contributing factors. These genetic components can reflect polygenetic
      mechanisms or a major gene effect. During recent years, polymorphisms of the
      genes governing both angiotensin converting enzyme (ACE) and angiotensinogen have
      been studied, with varying outcomes. Investigation of the interaction between ACE
      inhibition and the glycemic state yields equally interesting results. In healthy
      subjects on a high salt diet, the hyperglycemic state produced significant
      increases in renal plasma flow (RPF) in response to administration of the ACE
      inhibitor captopril. A similar study using the angiotensin receptor blocker (ARB)
      eprosartan demonstrated again that the agent had little effect on RPF in subjects
      in a normal glycemic state; however, when administered during a hyperglycemic
      state, a marked increase in RPF occurred. Implications for the prevention of
      nephropathy and endstage renal disease (ESRD) in diabetics with hypertension are
      significant. Until recently, pharmacologic intervention in the RAS has focused on
      the ACE step, with documented success being reported in the prevention of
      diabetic nephropathy and ESRD using ACE inhibitors. Despite this success, data
      suggest that greater therapeutic benefit might be accomplished by blocking the
      deleterious effects of angiotensin II at the receptor site. From a renoprotective
      perspective, the ARB appear to have tremendous potential in the management of
      hypertension.

PMID- 11459213
TI  - Pharmacology and clinical efficacy of angiotensin receptor blockers.
AB  - The treatment of hypertension has become increasingly refined during the past
      decade. Although a variety of antihypertensive medication classes exist, drugs
      that interrupt the renin-angiotensin axis have gained a favored position in the
      treatment of hypertension and its attendant end-organ complications. In this
      regard, two drug classes, angiotensin converting enzyme inhibitors and
      angiotensin receptor blockers, are most commonly used. Angiotensin receptor
      blockers have proven highly effective in the management of hypertension. This
      class is fairly heterogeneous with individual class members having somewhat
      distinctive pharmacologic properties. Eprosartan is a recent entry into this
      class. This compound compares favorably to others in this class relative to blood
      pressure reduction. In addition, preliminary studies indicate that this compound
      may uniquely interrupt the sympathetic nervous system and thereby preferentially
      reduce systolic blood pressure.

PMID- 11459214
TI  - The regulation of elongation by eukaryotic RNA polymerase II: a recent view.
AB  - The elongation of mRNA by RNA polymerase II (RNAPII) is controlled by the diverse
      actions of cis- and trans-acting elements that respond to a variety of biological
      signals. Elongation regulation, which determines the processivity of RNAPII,
      occurs during the steps of transcription initiation and elongation through both
      negative and positive influences. It has been generally accepted that negative
      elongation factors repress the elongation reaction. It is also generally accepted
      that positive elongation factors act by allowing the stalled RNAPII to escape
      from an inactive state, thus facilitating the production of full-length
      transcripts. However, recent data suggests that these opposing regulatory
      mechanisms can be achieved through a coupling pattern, rather than through
      independent activity. In addition, biochemical experiments using 5,6-dichloro-1
      beta-D-ribofuranosylbenzimidazole (DRB) have identified several factors involved
      in DRB-sensitive transcription, and elucidated the mechanism of interplay between
      the positive and negative elongation factors. Here, we will review the major
      findings from studies on RNAPII elongation control. We will further discuss the
      properties of newly identified factors that have resulted from studies on the
      action of DRB on elongation.

PMID- 11459215
TI  - A rapid screen for putative mislocalization mutations by using a GAL4-hybrid
      protein.
AB  - A GAL4 one-hybrid system was used to develop an indirect assay for intracellular
      localization. The Kar1 protein, a component of the yeast spindle pole body (SPB),
      was shown to be targeted to the SPB by electron microscopic analysis, or indirect
      immunofluorescence methods. To assay localization of the Kar1p by measuring the
      reporter gene expression on solid media, we constructed Kar1-Gal4 hybrid proteins
      with or without the SPB localization domain. The long fusion Kar1(299)-Gal4 with
      the localization domain led to non-growth on SC-His + AT media, and quite a low
      level of the lacZ reporter gene expression. The short fusion Kar1(107)-Gal4
      without the localization domain caused a full activation of the reporter genes,
      HIS3 and lacZ, indicating that the protein remains in the nucleoplasm. These
      results suggest that the Kar1(299)-Gal4p fusion protein, localized to the SPB,
      can be clearly differentiated with the mislocalized protein by assaying the
      reporter gene expression. By utilizing the Kar1(299)-Gal4 construct, we isolated
      ten spontaneous mutations that were defective in the Kar1-Gal4p localization.
      Four of these mutations were in the same complementation group. We propose,
      therefore, that the Gal4-hybrid localization assay can be utilized in cases where
      the target organelle or the structure is too small for microscopic analysis, or
      in the initial screening for mutations defective in localization.

PMID- 11459216
TI  - Characterization of a novel allele of glucose oxidase from a Korean wild type
      strain of Aspergillus niger.
AB  - We have identified a novel allele of the glucose oxidase (GO, EC1.1.3.4) gene
      (GO) from a Korean wild type strain of Aspergillus niger, ACMO4, with an
      increased GO activity in culture filtrate. Southern blot analyses of GO from
      ACMO4 (GO-ACMO4) revealed that the gene was present as a single copy in the
      genome of A. niger. However, its sequence differs from that of GO from A. niger
      ATCC 9029 (GO-ATCC9029). GO-ACMO4 appears to be a functional gene based on the
      fact that it is enzymatically active when heterologously expressed in yeast.
      Sequence comparisons of the coding region of GO-ACMO4 revealed 16 nucleotide
      changes that resulted in four amino acid substitutions; T432D, G517D, G530S, and
      Q542R. The GO proteins from both ATCC 9029 and ACMO4 were heterologously
      expressed, purified, and compared biochemically. The two enzymes showed no
      difference in their apparent Km value for glucose (30 mM), but the Vmax of GO
      ACMO4 (515.6 unit/mg) was 10% higher than that of GO-ATCC 9029, resulting in a
      10% higher specific activity.

PMID- 11459217
TI  - Activation of mouse B lymphocyte by proteins containing hexahistidine.
AB  - Many recombinant proteins are produced as a fusion protein tagging hexahistidine,
      which has been used for studying their biological function both in vitro and in
      vivo. Unexpectedly, we observed activation of BALB/c mouse splenocytes when
      treated with hexahistidine-tagged recombinant proteins. This activation was
      hexahistidine-specific since the anti-pentahistidine antibody completely
      neutralized the effect, and the bovine serum albumin conjugated with the
      hexahistidine peptides also showed a similar activation effect. The B cells
      seemed to be the activated splenocytes, since the cell population stained with
      the anti-immunoglobulin antibody and anti-CD80 antibody was increased after the
      treatment. However, the activation signal by hexahistidine was insufficient to
      fully differentiate the B lymphocytes. This result suggests that caution must be
      taken in the use of hexahistidine-tagged recombinant proteins, due to their
      nonspecific activation of B lymphocyte.

PMID- 11459218
TI  - Molecular characterization of Hmg2 gene encoding a 3-hydroxy-methylglutaryl-CoA
      reductase in rice.
AB  - Three genes encoding 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR, EC1.1.1.34),
      which converts HMG-CoA into mevalonate in the early key step of the plant
      isoprenoid pathway, were isolated by RT-PCR and rice cDNA and genomic library
      screening. A genomic Southern blot analysis confirmed that HMGR genes are present
      in three copies in rice. Of the three, the HMGR 2 gene (Hmg2) obtained as a cDNA
      clone and its genomic clone had 4 exons and 3 introns, and encoded a 576 amino
      acid peptide containing an open reading frame of 1,728 bp with a calculated Mw.
      of 61,150. The structure of rice Hmg2 had common features, based on its
      nucleotide and deduced amino acid sequence homologies, with other plant HMGR
      genes published to date. Rice Hmg2 transcripts were constitutively detected in
      all parts of the rice plant, except in lamina and their levels were high
      particularly in the leaf part of the dark-grown seedlings and mature flowers. Our
      result showed that mRNA levels of rice Hmg2 were strongly induced in seedlings
      and influorescence in the early development stage. Rice Hmg2 possibly has a
      housekeeping role involved in the sterol biosynthesis, among the possible roles
      of plant HMGR genes that have been suggested in other plants [Weissenborn et al.
      (1995)].

PMID- 11459219
TI  - In vitro selection of RNA against kanamycin B.
AB  - Aminoglycosides are well-known antibiotics that function by interacting with
      ribosomal RNA in bacteria. In order to understand the molecular details between
      RNA and the drug, RNA aptamer was selected against kanamycin B. After 12 cycles
      of selection, RNA was cloned and sequenced. Among 9 clones, sequences of three
      clones were identical, suggesting the selected RNA was enriched. Among the cloned
      RNA molecules, the triplicated RNA was the maximum binding RNA. It showed a 180
      nM affinity (KD) to the cognate aminoglycoside, as measured by a surface plasmon
      resonance, and a competition assay using a fluorescence anisotropy technique. The
      affinity of the maximum binding RNA to a similar aminoglycoside, tobramycin, was
      much stronger than 12 nM of KD. The binding site of the aminoglycoside in the
      maximum binding RNA was a stem loop located at the end of the 5' region. A stem
      loop structural motif, found in this study, was similar to those previously
      reported, even though the sequences of the RNA were totally different from the
      known sequences of the aminoglycoside binding site of other aptamers. The present
      study suggests that the aminoglycoside-binding region in RNA does not have a
      sequence specificity, but has a shape-specific bulged stem loop, even though it
      has a nanomolar affinity.

PMID- 11459220
TI  - Presumptive mechanisms of peptic ulceration by Helicobacter pylori VacA involving
      mucoprotease and CagA.
AB  - Helicobacter pylori vacuolating toxin (VacA) appears to be unusually stable, not
      only against extreme pH conditions or high temperatures, but also against common
      organic solvents or detergents. Under acidic conditions, its activity was
      markedly increased in the manner of temperature-independent, suggesting a
      spontaneous activation. A similar finding was also observed under alkaline
      conditions, however, it should have an appropriate temperature. From these
      observations, the mechanisms of VacA activation were suggested to be so redundant
      that either the case of acidic or basic amino acid residues could be involved in
      the VacA activation. Separately, we also found that the VacA production by H.
      pylori was pH-dependent: Its production was increased at a low pH region with a
      broad range (1.0-5.0), and at a high pH region with a narrow range (8.0-9.0).
      Astonishingly, a highly immunogenic CagA did not appear to be expressed under the
      acidic conditions. Its expression, however, was shown to be enhanced when the
      surrounding pH of this bacterium was raised. In contrast, mucoproteolytic
      activity in the H. pylori membrane was found to be increased at acidic
      conditions. Considering these observations, together with the stomach and
      duodenal pH of humans, two presumptive mechanisms of H. pylori VacA-associated
      ulceration may be deduced; namely, an acid- and an alkali-dependent type,
      involving mucoprotease and CagA, respectively.

PMID- 11459221
TI  - Comparative studies on the GABA-transaminase immunoreactivity in rat and gerbil
      brains.
AB  - Gamma-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter
      in the central nervous system (CNS). Degradation of GABA in the CNS is catalyzed
      by the action of GABA transaminase (GABA-T). However, the neuroanatomical
      characteristics of GABA-T in the gerbil, which is a useful experimental animal in
      neuroscience, are still unknown. Therefore, we performed a comparative analysis
      of the distribution of GABA-T in rat and gerbil brains using
      immunohistochemistry. GABA-T immunoreactive neurons were observed in the regions
      which contained GABAergic neurons of both animals: corpus striatum; substantia
      nigra, pars reticulata; septal nucleus; and accumbens nucleus. GABA-T + neurons
      were restricted to layers III and V in the rat. Unlike the rat GABA-T + neurons
      were observed in layers II, III, and V of the gerbil cerebral cortex. These
      results suggest that the expression of GABA-T in the gerbil brain may be similar
      to that in the rat brain, except in the cerebral cortex.

PMID- 11459222
TI  - Production of transgenic male sterile tobacco plants with the cDNA encoding a
      ribosome inactivating protein in Dianthus sinensis L.
AB  - The ribosome inactivating protein (RIP) gene from D. sinensis was used as a
      cytotoxin gene to induce male sterility in tobacco plants. The TA29 promoter,
      obtained by PCR amplification from tobacco, was fused to the RIP cDNA, and the
      chimaeric molecule was then introduced into tobacco plants by Agrobacterium
      mediated transformation. Out of twenty-one independent transformants, twenty
      transgenic tobacco plants exhibited male sterility. Southern blot analysis
      revealed that four of the transgenic plants contained a single copy of the RIP
      gene, while the rest of the transgenic tobacco plants had two to four copies of
      the gene. The transgenic male sterile plants set seeds normally when pollinated
      with pollens from untransformed control plants, indicating that the RIP gene does
      not affect the pistil development. Furthermore, the seed yield of the transgenic
      plant was similar to that of the untransformed, self-pollinated control plant. A
      light microscopic observation of anther cross sections clearly showed that the
      tapetal tissue of the anther was selectively and completely destroyed causing
      male sterility. This study suggests that the RIP gene can be used as a cytotoxin
      gene for induction of male sterility in the plant.

PMID- 11459223
TI  - Rapid detection of multiple nucleopolyhedroviruses using polymerase chain
      reaction.
AB  - A technique using the polymerase chain reaction (PCR) was developed for detection
      of the nucleopolyhedrovirus (NPV) polyhedrin gene. The amino acid sequences of
      the polyhedrin gene were compared in twenty-six NPVs. A highly conserved DNA
      sequence within the coding region of the polyhedrin gene was targeted for
      amplification. One pair of degenerate PCR primers was designed to produce
      fragments of about 430 bp. The NPVs detected by this technique were Autographa
      californica NPV, Bombyx mori NPV, Hyphantria cunea NPV, Spodoptera exigua NPV, S.
      litura NPV, and Lymantria dispar NPV. This technique would be useful in
      monitoring the distribution of NPVs and release of the wild type and recombinant
      NPVs.

PMID- 11459224
TI  - Effect of alpha1-acid glycoprotein expressed in cancer cells on malignant
      characteristics.
AB  - The alpha1-acid glycoprotein (AAG) is a prototypical serum acute phase reactant
      in most mammalian species; it is synthesized mainly in liver parenchymal cells.
      Recently, we found that mRNAs of AAG were expressed in non-hepatic cancer cells,
      and the expression levels were regulated by the cytokines--IL-1, IL-6, and TNF
      alpha. The functional role of AAG in non-hepatic cancer cells has not yet been
      established. In order to understand the functional role of the AAG expressed in
      HT-29 cells, the cancer cells were transfected with cloned cDNA for AAG, or
      exposed to antisense oligodeoxynucleotide (ODN) for AAG. The colony-forming
      capacity, invasion, and adhesion to laminin of these transformed cancer cells
      were measured. Overexpression of AAG by transfection, and inhibition of the AAG
      expression by antisense ODNs were identified by Western blot as well as nested
      reverse transcriptase-polymerase chain reaction (nested RT-PCR), respectively.
      Results showed that the overexpression of AAG by transfection reduced colony
      forming capacities, invasion, and adhesion to laminin of the cancer cells; on the
      other hand, the antisense ODN for AAG elevated colony-forming capacities,
      invasion, and adhesion to laminin of the cancer cells. These results suggest that
      AAG, expressed in cancer cells inhibited proliferation, invasion, and metastasis
      of the cancer cells.

PMID- 11459225
TI  - Developmental patterns of ceramide glucosyltransferase (GlcT-1) expression in the
      mouse: in situ hybridization using DIG-labeled RNA probes.
AB  - Glycosphingolipids (GSLs) play significant roles in a variety of cell membrane
      events, including cellular interactions, signaling, and trafficking. Ceramide
      glucosyltransferase (glucosylceramide synthase, GlcT-1, EC 2.4.1.80) catalyzes
      the initial step in GSL synthesis, the transfer of glucose from UDP-glucose to
      ceramide. The reaction product of glucosylceramide serves as a core structure for
      over 400 species of GSLs. The enzyme is a key regulatory factor controlling
      intracellular levels of ceramide and GSLs. Appearance and differential
      distribution of GlcT-1 mRNA during mice postimplantation embryogenesis [embryonic
      (E) days; E9, E11, E13, E15] were investigated by in situ hybridization with
      digoxigenin-labeled RNA probes, coupled with alkaline phosphatase detection. On
      E9, tissues of the mesencephalon, myelecephalon, diencephalons, and telencephalon
      expressed GlcT-1. On E11, it was expressed to a detectable extent in various
      tissues including mesencephalon, myelecephalon, diencephalon, telencephalon,
      nose, lung, liver, vertebra, tail, spinal cord, and tongue. The expression
      patterns of E13 were similar to those of E11, except that the heart and stomach
      became positive. On E15, a specific signal for GlcT-1 was detected in all organs
      of the embryo. These results provide the first evidence that GlcT-1 is
      differentially expressed during postimplantation embryogenesis.

PMID- 11459226
TI  - Characterization of MADS box genes from hot pepper.
AB  - The cDNA clone, CanMADS1, was isolated from young flower buds of the hot pepper
      (Capsicum annuum L.) by screening a cDNA library using the OsMADS1 rice MADS-box
      gene as a probe. We used a yeast two-hybrid screening method to investigate
      interaction partners of the protein product of CanMADS1. A MADS-box gene,
      CanMADS6, was isolated from young flower buds using the region containing the K
      domain and 15 amino acid residues of the C-terminal region of CanMADS1 as a bait.
      CanMADS1 and CanMADS6 showed high amino acid sequence similarities to members of
      the AGL2 subfamily and the SQUA subfamily, respectively. CanMADS1 transcript was
      expressed in flower buds and fruits, and the transcription signal was the
      strongest in the stage of the fruit set (2 d after anthesis). CanMADS6 showed the
      same expression pattern as CanMADS1. CanMADS1 and CanMADS6 were not expressed in
      leaves. These results suggest that a regulatory role for flower and fruit
      development of the hot pepper may be accomplished through an interaction of the
      protein products of the two MADS-box genes, CanMADS1 and CanMADS6.

PMID- 11459227
TI  - Molecular cloning and characterization of groESL operon in Streptococcus
      pneumoniae.
AB  - GroEL is a major target of the immune defense in infection and seems to be
      negatively regulated by HrcA in gram-positive organisms. However, HrcA's
      mechanism has not been elucidated. To elucidate the role of groEL in
      Streptococcus pneumoniae, the groESL operon was cloned in Escherichia coli. The
      promoter region of the pneumococcal groESL operon contained a sigmaA type
      promoter and an inverted repeat (CIRCE). A Northern blot analysis of the groESL
      operon demonstrated that the groESL operon is transcribed as a bicistronic mRNA,
      and reached maximum expression 7.5 to 10 min after heat shock. A primer extension
      analysis showed a potential transcription start point at 155 bp upstream of the
      translation start site, preceding the groES gene. The putative negative regulator
      of the groEL gene, hrcA, of S. pneumoniae was recovered by PCR-based chromosomal
      walking from grpE locus. A sequence analysis showed a sigmaA type promoter
      flanked by 2 CIRCE elements. His-tagged HrcA was overexpressed as a soluble form
      in E. coli and bound to the CIRCE regions in the promoter of both groESL and dnaK
      operons in vitro. Additionally, a helix-loop helix motif, a putative DNA binding
      domain, was found at the C-terminal of HrcA. These results will help to determine
      the nature of HrcA in the groESL repression.

PMID- 11459228
TI  - Differential tyrosine phosphorylation of phospholipase D isozymes by hydrogen
      peroxide and the epidermal growth factor in A431 epidermoid carcinoma cells.
AB  - The regulatory mechanism through which the phospholipase D (PLD) isoforms PLD1
      and PLD2 are activated is poorly understood. We investigated the possibility that
      the PLD isozymes are differentially regulated in response to pharmacologic
      stimulants in cells. In this report, we demonstrate for the first time that H2O2
      and EGF differentially induce tyrosine phosphorylation of the PLD isozymes in
      A431 cells, which express both PLD1 and PLD2. H2O2 induced tyrosine
      phosphorylation of PLD1 and PLD2, whereas EGF only caused the tyrosine
      phosphorylation of PLD2. Both agents also induced phosphorylation of the EGF
      receptor. Interestingly, the PLD isozymes were associated with the EGF receptor
      and PKC-alpha in a ligand independent manner. Activation of PLD by H2O2 and EGF
      nearly correlated with tyrosine phosphorylation of the protein in PLD1 immune
      complexes. Activation of PLD by both agents was inhibited by the PKC inhibitor,
      Ro 31-8220, and by the down-regulation of PKC. Pretreatment of the cells with the
      tyrosine kinase inhibitor tyrphostin AG1478 resulted in inhibition of the H2O2
      and EGF-induced tyrosine phosphorylation and PLD activation. These results
      indicate that H2O2 and EGF induce differential tyrosine phosphorylation of PLD
      isozymes. Also, the activation of PLD by these agonists involves tyrosine
      phosphorylation and PKC activation.

PMID- 11459229
TI  - Testis-specific expression of an intronless gene encoding a human poly(A)
      polymerase.
AB  - A mouse intronless gene, encoding a testis-specific poly(A) polymerase (mPAPT),
      was previously identified. mPAPT may play a role as a putative enzyme that is
      responsible for polyadenylation regulation during mouse spermatogenesis. In order
      to understand how PAPT genes are conserved in mammals, we isolated a human cDNA
      homolog encoding a human PAPT (hPAPT), which was specifically expressed in the
      testis. The structure of hPAPT was very similar to that of mPAPT. The about 100
      residues at the C-terminal region of a nuclear poly(A) polymerase, PAP II, were
      missing in both PAPT proteins. An analysis of the genomic DNA showed that the
      hPAPT gene is an intronless gene that is similar to the mPAPT gene.
      Interestingly, the sequence homology between hPAPT and mPAPT was much lower than
      the homology between hPAP II and mPAP II. The phylogenetic analysis suggests that
      PAPTs arose through retrotransposition after the amphibian-amniote split during
      evolution.

PMID- 11459230
TI  - Altered expression of phospholipase D1 in spontaneously hypertensive rats.
AB  - To clarify the involvement of phospholipase D (PLD) in the mechanism underlying
      genetically-induced hypertension, we investigated the activity and expression
      levels of PLD in tissues taken from spontaneously hypertensive rats (SHR), and
      their normotensive controls, Wistar-Kyoto rats (WKY). The ADP-ribosylation factor
      3 (ARF3)-dependent PLD activity and protein levels of PLD1 from SHR increased
      significantly in the brain and liver, but not in the heart and kidney, compared
      to those of WKY. The activity and expression of PLD were the same between the
      homogenated whole kidneys of the two strains; however, there were topographical
      differences in the expression and activity of PLD between the kidneys of the two
      strains. The activity and expression level of PLD gradually increased from the
      cortex to the inner medulla of WKY. The enzyme activity, and amount of PLD in the
      inner stripe of the outer medulla and in the inner medulla, was significantly
      lower in SHR than in WKY. Taken together, these results suggest that the
      distinctly distributed patterns of PLD in the kidney may be associated with
      differential signal transduction pathways that are involved in hypertension in
      conjunction with an increase of PLD activity in the brain and liver.

PMID- 11459231
TI  - Increase in the expression of human leukocyte antigen class I in human
      fibroblasts by soluble factors secreted from human cytomegalovirus-infected
      cells.
AB  - The human cytomegalovirus (HCMV) is known to downregulate the expression of the
      human leukocyte antigen (HLA) class I for escape from immune surveillance. In
      order to understand the HCMV immune evasion mechanism, expression of HLA class I
      on the surface of HCMV-infected cells was investigated. A decrease in the HLA
      class I expression was observed at higher MOI; whereas at a lower MOI a slight
      increase in the HLA class I expression was observed. When HCMV-infected and
      uninfected cells were separately prepared on coverslips and co-cultured, the
      increased HLA class I expression was observed in uninfected cells. Treatment of
      the uninfected cells with the culture supernatant from HCMV-infected cells
      resulted in an increase in the HLA class I expression. A biochemical analysis of
      the HCMV-infected cell culture supernatant revealed the presence of interferon
      (IFN) beta interleukin (IL)-1beta, and IL-6. The HLA class I-enhancing activity
      of the culture supernatant was mimicked by IFN beta, but not by IL1-beta or IL-6,
      and was partially reversed by pretreatment with an antibody to IFN beta.
      Therefore, it appears that the HCMV infection of human foreskin fibroblast cells
      induces interferon beta and other soluble factor(s) that are responsible for the
      up-regulation of the HLA class I expression.

PMID- 11459232
TI  - Modulation of catalase in human skin in vivo by acute and chronic UV radiation.
AB  - In this study, we demonstrate that catalase is differently regulated either by
      acute, or chronic UV radiation during the photoaging process. 2MED of UV
      radiation decreased the activity and expression of catalase gradually in the
      epidermis and dermis at between 24 and 48 h after the UV exposure. These levels
      then returned to near normal by 72 h after exposure. The catalase mRNA was also
      decreased in the skin 24 h after UV irradiation to 50% of the control level, and
      then started to recover. In contrast, chronic UV irradiation over a lifetime
      (approximately 50 years) increased the catalase activity in the epidermis and
      dermis of the human skin in vivo. Our results suggest that catalase might be one
      of the important enzymes in the skin aging process, and that it plays an
      important role in the photoprotection of the skin from UV light.

PMID- 11459233
TI  - Cloning and sequence analysis of Gpdh in Callosobruchus chinensis (Coleoptera:
      Bruchidae).
AB  - The Sn-Glycerol-3-phosphate dehydrogenase (GPDH: NAD+ 2-oxidoreductase, EC
      1.1.1.8) gene of C. chinensis was cloned and its nucleotide sequence was
      analyzed. The gene was obtained by screening a genomic library with Drosophila
      melanogaster Gpdh and PCR amplification. The 5,126 bp gene obtained is comprised
      of one 5' untranslated region, eight exons, seven introns, and three 3'
      untranslated regions. Comparison of Gpdh of D. melanogaster with that of C.
      chinensis showed a 89.9% identity in the coding region, 70% in the intron, 79% in
      the entire nucleotide sequence, and 83.2% in the deduced amino acid sequence. The
      transcription initiation site is located 33 nucleotides upstream of the
      initiation codon, and the sequence analysis of the promoter region showed TATA
      and CAAT boxes at the 5' end. The stop codon (TAA) and polyadenylation signal
      (AATAAA) are located at the 3' end of each of the exons 6 to 8. These findings
      show that GPDH isozymes in C. chinensis are produced by the alternative
      processing of 3' exons. The occurrence of the three transcripts was proven by RT
      PCR using synthetic oligonucleotides complementary to the predicted unique 3'
      regions. Compared to the D. melanogaster GPDH isozymes, GPDH-1, -2, and -3, C.
      chinensis GPDH showed 83.6%, 83%, and 84% identities, respectively.

PMID- 11459234
TI  - Increasing body size among adult cook islanders between 1966 and 1996.
AB  - There is limited evidence of a secular trend toward increased body size among
      populations in the Pacific Region, although some populations have shown a clear
      rise in overweight and obesity across the past 30 years or so. Mean height,
      weight and body mass index (BMI) of adults surveyed in 1996 on Rarotonga, the
      Cook Islands, are reported by age group and compared with data collected in 1966
      by Evans and Prior, to determine the extent to which a secular trend in
      increasing body size has taken place across this 30-year period. In addition, a
      comparison of these anthropometric variables between subjects born on the most
      modernized island of Rarotonga with those born on other less-modernized islands
      is made, to determine the extent to which adult body size differs according to
      place of origin. Comparing the sample of those born on Rarotonga, the most
      modernized island, with those born on other, less modernized islands shows those
      born on Rarotonga to be taller, but not relatively heavier than those born
      elsewhere in the Cook Islands. Both males and females of the 1996 sample of
      adults are significantly taller, heavier, with higher BMI compared with the 1966
      sample, indicating a secular trend toward increased body size across this 30-year
      period. The mean BMIs of the younger age groups in 1996 are greater than those of
      the same age groups in 1966, indicating a secular trend toward greater body
      fatness. There has been a significant increase in obesity among both males and
      females. In 1966, 14% of males had a BMI greater than 30, while in 1996, the
      proportion was 52%. Among females, 44% of those measured in 1966 had a BMI
      greater than 30, while in 1996 the proportion was 57%. The higher mean stature of
      younger adult males relative to older ones suggests that the secular trend toward
      increasing height may have been underway prior to 1966. The mean statures and
      weights of adults aged 60 years and older in the 1996 sample are more similar to
      values given for most age groups in the 1966 sample, indicating that the secular
      trend toward increased weight and height may have begun 50-60 years ago.

PMID- 11459235
TI  - Body mass index of adult males in 12 populations of northeast India.
AB  - BACKGROUND: Of the anthropometric indices, body mass index (BMI) is considered to
      be more nutritionally than genetically related. Thus, in a country with diverse
      ethnic groups like India, it is more appropriate to use BMI as an indicator of
      the nutritional status of adult population. However, literature on BMI of adult
      Indians is limited to certain geographical regions or populations, and little is
      known about the populations in the northeast region of the Indian sub-continent.
      AIM: The present report deals with the BMI of adult males in 12 populations of
      Northeast India with a view to understanding their nutritional status. SUBJECTS
      AND METHODS: Anthropometric data collected by the Anthropological Survey of India
      on 946 adult males aged 18-62 years of 12 populations in Northeast India were
      used in this analysis. The populations were broadly categorized into three
      groups, namely, caste. Hinduized and tribal groups. The data were collected
      mostly from rural areas, taking into consideration the different social ranks
      such as castes, tribes and religious groups. RESULTS: The variation in mean BMIs
      between populations was highly significant, ranging between 18.3 and 20.5 kg m(
      2). Despite a few exceptions, the mean values of BMI in the tribal populations
      were significantly higher than the caste groups. The prevalence of chronic energy
      deficiency (CED) was also lower in the tribal (19%) than in the Hinduized (49%)
      and caste (52%) populations (chi2 = 89.4, d.f. = 2, p < 0.001). Although it is
      difficult to explain why the tribals have higher BMI than the higher castes, the
      Cormic index or CI (SH/H) was significantly lower among the caste groups as
      compared with some tribal groups. The linear regression coefficient (b +/-
      standard error) of BMI on CI for all the populations, irrespective of ethnic
      origin, was 30.4+/-4.3 (t = 7.1, p < 0.000). and the correlation coefficient (r
      +/- standard error) 0.22+/-0.03. The differences in BMI across groups were,
      however, significant even after allowing for CI. CONCLUSION: A majority of the
      adult males in these populations were lean. The high proportion of individuals
      with grade I CED suggests the need of other information on morbidity and health
      status of these populations.

PMID- 11459236
TI  - Growth of urban school children in Malawi.
AB  - The objective of this cross-sectional study was to assess growth pattern of urban
      school children in Malawi from low socio-economic strata and to compare
      anthropometric measurements of the children to data from the region of South
      Central Africa and to international standards. A total of 493 urban school
      children aged 6-17 years were selected randomly from two primary schools in semi
      urban Blantyre, the largest city in Malawi. Anthropometric measurements included
      height, weight, mid-upper arm circumference, triceps skinfold thickness, mid
      upper arm muscle circumference and maximal grip strength of the stronger hand.
      All parameters of Malawian children of both sexes were lower than medians of
      WHO/NCHS reference data. Expressed as percentage of WHO/NCHS references, the
      relative means of height, weight, mid-upper arm circumference and mid-upper arm
      muscle circumference of Malawian girls were considerably higher than those of
      boys, and older girls had better parameters than younger ones. Older pupils of
      both sexes had higher triceps skinfold thickness relative to the international
      references than the younger children. Mean maximal grip strength values of boys
      and girls were not significantly different. For girls, the relative values
      increased with age, while for boys they decreased. It is concluded that younger
      primary school pupils have similar body sizes to their counterparts from the
      region. Adolescents, particularly girls, have more favourable anthropometric
      parameters which approach WHO/NCHS reference data.

PMID- 11459237
TI  - Statistical characterization of the pubertal growth spurt.
AB  - BACKGROUND: This is a methodical investigation into the problem of estimating
      parameters for the pubertal spurt (PS). The variability involved in determining
      the timing, intensity and duration of the PS for height, leg height and biiliac
      width is estimated via a realistic simulation. Further, a decomposition of
      adolescent growth into a component due to the pubertal peak and one due to
      ongoing prepubertal velocity is evaluated. METHODS: Data for 120 boys and 112
      girls are available from 4 weeks to adulthood. The curve-fitting method is kernel
      estimation for distance, velocity and acceleration. RESULTS: The age of peak
      velocity and the age of stopping of the PS are well determined. In contrast, the
      age of onset of the PS is less well determined. Intensity is less variable for
      the parameter peak velocity than for maximal acceleration. It is feasible to
      decompose adolescent growth into a component due to the pubertal peak and one due
      to ongoing prepubertal growth. CONCLUSIONS: Nonparametric curve-fitting methods
      which do not rely on a parametric growth model can be successfully used to
      extract individual characteristics of the PS.

PMID- 11459238
TI  - Mixed distribution analysis identifies saltation and stasis growth.
AB  - A maximum likelihood method of mixed distribution analysis is investigated for
      its utility as a method for the identification of saltation and stasis in
      longitudinal growth data. Daily infant growth data that have been previously
      identified to follow a saltatory growth process are employed. This is a novel
      application of the finite mixed distribution analysis (MDA), a method designed to
      objectively identify the presence of one or more Gaussian populations. The null
      hypothesis is that a single Gaussian distribution best describes the incremental
      growth data. This would be compatible with smooth, slowly varying daily growth
      patterns. This study explores whether or not two distinctive populations are
      evident in incremental saltatory growth data, as postulated by the saltation and
      stasis observations. The analysis is important in providing a growth model
      independent test for the presence of saltation and stasis by a separate
      statistical assessment with none of the saltatory algorithm assumptions. The
      finite mixed distribution analysis identifies that each individual's incremental
      growth data is statistically best described as a mixture consisting of two
      components, or two populations of increments (chi-square, p < 0.05). For each
      individual, one of these populations is centred about a zero increment, and is
      compatible with the previous evidence of stasis intervals. The second population
      of data points is characterized by unique distributions for each individual,
      compatible with the previous observation that infants grow by unique patterns of
      growth saltations in both amplitude and frequency. The percentage of data points
      that fall within each of the two unique finite mixture distributions (FMDs) is
      similar to the proportions of discrete saltation and stasis intervals previously
      identified by the saltation and stasis method. Thus, the FMD analysis lends
      support to the nature of growth as a saltatory process characterized by two
      states in the daily growth of these infants. By contrast with the saltatory
      algorithm, which is applied to the original serial growth measurements, the mixed
      distribution analysis employs increments removed from their time relationships.
      The lack of time series sequence information precludes the mixed distribution
      method from reconstructing specific temporal patterns of saltatory growth. The
      present analysis reiterates that individual growth patterns are statistically
      unique and cannot be reconstructed or identified from group data.

PMID- 11459239
TI  - Relation between commuting, leisure time physical activity and serum lipids in a
      Chinese urban population.
AB  - PRIMARY OBJECTIVE: To analyse the association between both commuting and leisure
      time physical activity and serum lipids in a Chinese population. POPULATION: A
      total of 1786 males and 1922 females aged 20-49 years. METHODS: A cross-sectional
      survey was carried out in 1989 in urban area of the city of Tianjin, China.
      Commuting and leisure time physical activity, total cholesterol, high density
      lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides
      were determined. RESULTS: Daily walking or cycling to and from work was inversely
      associated with serum total cholesterol, low-density lipoprotein cholesterol and
      triglyceride concentrations among men and positively associated with high-density
      lipoprotein cholesterol concentrations among women as compared to travelling to
      and from work by bus. CONCLUSIONS: The present study showed a significant
      association between serum lipids and commuting physical activity, but no relation
      with leisure time sports.

PMID- 11459240
TI  - Strategies for combining and scaling sexual maturity indicators: the Heartfelt
      Study.
AB  - PRIMARY OBJECTIVE: To identify the best variable or combination of sexual
      maturity variables to use in investigations of adolescent health, and explore
      possible re-scaling of five-stage sexual maturity stages into dummy variables'
      ('advanced'/'delayed'). RESEARCH DESIGN: Cross-sectional. SUBJECTS: Tri-ethnic
      sample of 384 US adolescents 11-16 years of age (Heartfelt Study). METHODS:
      Sexual maturity variables are genital. breast and pubic hair stages obtained by
      clinical examination by nurse practitioners, testes size, menarche and age at
      menarche. RESULTS: Principal factor analysis of sexual maturity variables, height
      and age, revealed high commonality among the variables, as no more than a single
      factor appeared in 27 of 28 factor analyses (by sex and age groups). Genital
      stage (boys) and breast stage (girls) were most highly related to the first
      principal factor independent of age and ethnicity. ANOVA of 'key variables'
      indirectly reflecting endocrine function suggested that some stages could be
      combined. CONCLUSIONS: A single variable should suffice to describe sexual
      maturity at the studied ages, or variables could be combined in a
      (unstandardized) sexual maturity index (SMI): SMI (Girls)=0.998 x BREAST+0.900 x
      PUBIC HAIR + 1.815 x YEARS SINCE MENARCHE. SMI (Boys)= 1.104 x GENITAL + 1.328 x
      PUBIC HAIR + 5.997 x TESTES SIZE (mL).

PMID- 11459241
TI  - The HUMFIBRA (FGA) polymorphism in an italian population and a world-wide
      frequency distribution analysis.
AB  - OBJECTIVE: The study investigated the highly polymorphic HumFGA short tandem
      repeat in a sample of 219 unrelated and native individuals from Bologna, and
      analysed a complete database of FGA allele frequency distributions in 57 world
      wide populations collected from the literature. METHOD: The HumFGA polymorphism
      was screened by automated fluorescence analysis of PCR-amplified labelled sample
      fragments performed with an ABI PRISM 310 Genetic Analyser. Genetic distances
      (Dsw, delta mu2 and Fst) between populations were computed with the MSAT.2
      program. Non-metric multidimensional scaling (nmMDS) and neighbour-joining trees
      (NJTs) were used to investigate patterns of population affinities. Correspondence
      analysis of the genetic relationships among populations was also performed. MAIN
      RESULTS AND CONCLUSIONS: The FGA microsatellite locus is a population marker with
      a high degree of polymorphism throughout the world. Fourteen HumFGA alleles,
      ranging in size from 18 to 29 repeats, were identified and sequenced in the
      Bologna population. The sample was in Hardy-Weinberg equilibrium and had a
      heterozygosity value of 0.86. Results obtained from the multivariate analyses
      were consistent in showing great similarity among Europeans. The few African
      populations investigated were characterized by an even higher level of
      polymorphism, probably related to the ancient peopling of that continent.

PMID- 11459242
TI  - Relationship between self-reported food and fluid intake and menstrual
      disturbance in female recreational runners.
AB  - A 1 year prospective study was conducted in France in 1993-1994 to examine the
      extent of menstrual cycle impairment in a sample of recreational French runners,
      and to relate the extent of impairment to dietary characteristics. The runners
      provided 7-day weighed food and fluid intake at intervals of 3 months during the
      year, as well as full details of their menstrual cycles and training schedules.
      The food survey commenced with 34 runners and 21 provided information on all four
      occasions. About 6% of the women, at any session, unrealistically report their
      dietary intakes. However, there was no evidence of any relationship between
      extent of under-reporting and menstrual status. The sample was divided into three
      menstrual cycle groups of eumenorrhoeic, irregular and amenorrhoeic (including
      oligomenorrhoeic). No significant differences in mean energy intake,
      carbohydrate, fat and protein intakes were found between groups. However, there
      were very marked differences in fluid and fibre intake, with amenorrhoeic and
      oligomenorrhoeic runners consuming about twice the mean daily fluid intake of
      eumenorrhoeic or irregularly menstruating groups.

PMID- 11459243
TI  - Some factors affecting marital isonymy in three Outer Hebridean parishes.
AB  - Log linear analysis was used to investigate the relationships between spouse
      isonymy and parental isonymy, time, endogamy/exogamy and groom's occupation in a
      total of 6266 first marriages of parish-born spouses in the civil parishes of
      Harris, Barra and Stornoway, between 1855 and 1990. Stornoway was divided into
      rural and urban (Burgh) components. Spouse isonymy comprised between 6% and 12%
      of all marriages, parental isonymy was generally slightly more frequent, due
      probably to the occurrence of occasional families in which both sets of parents
      were isonymous. Between 38% and 51% of marriages were endogamous. In the multi
      way contingency tables, good fits between observed and expected cell numbers were
      obtained by a simple model, comprising the main effect of spouse isonymy and the
      first-order interactions between spouse isonymy and the independent variables.
      Inspection of the coefficients showed that in all four populations spouse isonymy
      was positively related to parental isonymy (doubtfully so in the case of Barra).
      The other independent variables showed less clear-cut relationships-
      endogamy/exogamy in Barra, and groom's occupation in Stornoway Rural; time period
      showed no significant relationships. It is concluded that the occurrence of this
      'two-generational marital isonymy' might have an effect on the breeding structure
      of the population.

PMID- 11459244
TI  - Body mass index and the prediction of percentage body fat in Australian Chinese
      women.
AB  - BACKGROUND: Body mass index (BMI) is frequently related to percentage body fat.
      Nevertheless the relationship between BMI and fat mass/height2 (FM/H2),
      theoretically, should be more appropriate. AIM: This study seeks to evaluate the
      relationship between BMI and both percentage body fat and FM/H2 in a group of
      Chinese Australian females. SUBJECTS AND METHODS: Forty subjects took part in the
      study and all were Chinese females resident in Brisbane, Australia. Body mass
      index was calculated from height and weight. Percentage body fat and fat mass
      were calculated from measurements of total body water. RESULTS: The use of BMI to
      predict FM/H2 accounted for double the variance of that found when BMI was used
      to predict percentage body fat. CONCLUSIONS: As a consequence, it is possible
      that the use of BMI to predict FM/H2 and not percentage body fat in the first
      instance may prove to be more useful in a number of adult populations.
      Nevertheless, with a relatively small sample size it is difficult, if not
      impossible, to test the developed equations on a validation group and further
      investigation into the findings described in this paper needs to be undertaken.

PMID- 11459245
TI  - Recognizing and responding to a suicide crisis.
AB  - Data from therapists who were treating 26 patients when they committed suicide
      were utilized to identify signs that warned of a suicide crisis. Three factors
      were identified as markers of the suicide crisis: a precipitating event; one or
      more intense affective states other than depression; and at least one of three
      behavioral patterns: speech or actions suggesting suicide, deterioration in
      social or occupational functioning, and increased substance abuse. Problems in
      communication between patient and therapist were identified as factors
      interfering with crisis recognition. Evaluation of the identified affects and
      behaviors may help therapists recognize a suicide crisis.

PMID- 11459246
TI  - What would you say to the person on the roof? A suicide prevention text.
AB  - This anti-suicide text provides potential helpers (professional and lay) with
      clear guidelines for communicating with a declared suicidal person, particularly
      in real-time situations, when time is crucial and the act cannot be physically
      prevented. The text also may have a preventative effect when diffused to the
      public as an anonymous address to potential suicides.

PMID- 11459247
TI  - The course of post-crisis suicidal symptoms: how and for whom is suicide
      "cathartic"?
AB  - We investigated suicide "catharsis" as evidenced by decreased suicidality
      following a suicide attempt. Past research has examined this issue with mixed
      results (Bronisch, 1992; Davis, 1990; van Praag & Plutchik, 1985). In the present
      study, we examined Modified Scale for Suicide Ideation (MSSI) scores for 198
      suicidal men during suicidal crisis, prior to entry into a treatment study, and
      again at 1-month and 12-month follow-ups. Patients were divided into ideators,
      single attempters, and multiple attempters. We found evidence for decreased
      suicidality, but interpreted it as the gradual action of interpersonal support,
      rather than as emotional catharsis. Also, multiple attempt status affected the
      long-term course of post-crisis suicidality.

PMID- 11459248
TI  - Toward an integrative model of suicide attempt: a cognitive psychological
      approach.
AB  - Applying a cognitive approach, the purpose of the present study was to expand
      previous research on stress-vulnerability models of depression and problem
      solving deficits, as it relates to suicide attempt. Structural equation
      modelling, involving latent variables, was used to evaluate (a) whether low self
      esteem, a low sense of self-efficacy, loneliness, and divorce constituted
      vulnerability factors for the development of depression; (b) whether hopelessness
      and suicidal ideation mediated the relationship between depression and suicide
      attempt; and (c) whether problem-solving deficits mediated the relationship
      between the vulnerability factors and suicide attempt, separate from
      depression/hopelessness. A total of 123 individuals, aged 18-75 years,
      participated in the study (72 suicide attempters and 51 psychiatric outpatients
      with no history of suicidal behavior). The results indicated a two path model of
      suicide attempt. The first path began with low self-esteem, loneliness, and
      separation or divorce, which advanced to depression, and was further mediated by
      hopelessness and suicidal ideation which led to suicide attempt. The second path
      developed from low self-esteem and a low sense of self-efficacy and advanced to
      suicide attempt, mediated by a negative appraisal of one's own problem-solving
      capacity, and poor interpersonal problem-solving skills. The importance of
      addressing both depression/hopelessness, and problem-solving deficits when
      working with suicide attempters is noted.

PMID- 11459249
TI  - Psychosocial and pharmacological treatment of patients following deliberate self
      harm: the methodological issues involved in evaluating effectiveness.
AB  - Development of effective treatments for patients following deliberate self-harm
      (self-poisoning or self-injury) is a very important element in suicide
      prevention. The randomized controlled trial (RCT) is the mainstay of evaluation
      of treatments. In a systematic review of the literature, the effectiveness of
      treatments based on RCTs was examined and the quality of the RCTs was assessed.
      Twenty trials were identified, and where possible, these were grouped on the
      basis of similarities among the types of treatment. In this paper, we examine the
      methodological aspects of the trials and consider what may be learned that will
      assist in the design of future studies in this field. The methodological quality
      of the trials was reasonable, but most trials included too few participants to
      detect clinically important differences in rates of repeated self-harm. In
      planning future trials, the following major issues should be addressed:
      investigators should perform power calculations to determine the number of
      subjects necessary to detect clinically important effects, provide information on
      method of randomization and interventions, use standard measures of outcome, and
      focus on homogeneous subgroups of patients. Improving the methodology of future
      studies in this field will be essential if sound evidence is to be obtained which
      can inform effective service provision for deliberate self-harm patients.

PMID- 11459250
TI  - Alcohol use disorders and risk factor interactions for adolescent suicidal
      ideation and attempts.
AB  - Four hundred eighty-two adolescents who were diagnosed with at least one mental
      disorder were studied to determine the predictors of suicidal ideation and
      suicide attempts. Major depression was predictive of suicidal ideation and
      suicide attempts for both genders. Chronic stress was found predictive of male
      suicidal ideation, while low self-esteem and high family dysfunction were found
      to be predictive of suicidal ideation in females. Statistical trends suggest that
      females with comorbid alcohol use/conduct disorder were approximately three times
      more likely to have attempted suicide than those with only one of these
      conditions. Clinicians working with adolescents should be aware that, while
      depression remains the number one clinical risk forsuicidal behavior, risk
      factors for suicidal ideation may be different than those for attempted suicide
      and may vary by gender.

PMID- 11459251
TI  - Childhood trauma and suicidal behavior in male cocaine dependent patients.
AB  - A consecutive series of 100 male cocaine dependent patients were interviewed
      about suicidal behavior and completed the 34-item Childhood Trauma Questionnaire
      (CTQ) to determine whether childhood trauma is associated with suicidal behavior
      in cocaine dependent men. Patients who had attempted suicide (n = 34) reported
      significantly higher scores for childhood emotional abuse, physical abuse, sexual
      abuse, and emotional and physical neglect than patients who had never attempted
      suicide (n = 66). In this study, various childhood traumas were found to be
      significantly associated withsuicidal behavior among adult male cocaine dependent
      patients.

PMID- 11459252
TI  - Risk factors associated with overdose among Bahraini youth.
AB  - The aim of this study was to identify the risk factors of overdose among Bahraini
      youth (15-24 years). These factors included psychiatric disorders, family
      pathology, and psychosocial stress. All suicide attempters in the country during
      an 18-month period (N= 100) were identified prospectively. One hospital-matched
      control was selected for each case. Both cases and controls underwent a
      semistructured personal interview in the two state general hospitals. A matched
      pair analysis was done, as well as computation of McNemar's continuity corrected
      chi-square test, odds ratio, and the 95% confidence interval of the odds ratio.
      The overdose attempter was more likely than the control to be unemployed, a
      member of a non-intact family, having a mother whose education was high school or
      above, not having a friend, involved in a boy/girlfriend relationship, and a
      cigarette smoker. More students among attempters had failed an examination in the
      past year than matched controls. Father's education, social class, death of
      father, recent row with a friend, use of drugs and alcohol, relationship with
      teachers, recent mobility, financial difficulties, and legal problems were
      similar in both groups. Stresses generated from living in a non-intact family,
      interpersonal relationships mainly with the opposite sex, unemployment, and
      school performance came out as the main risk factors. The association of
      previously identified risk factors such as depression, aggressive behavior, and
      use of drug and alcohol was low among attempters. While the results of this study
      are consistent with the present view that suicidal behaviors are multifactorial
      in origin, the magnitude and effect of each factor are culturally determined.

PMID- 11459253
TI  - Suicidal ideation, psychiatric disorder, and medical illness in a community
      epidemiological study.
AB  - Many epidemiological studies have analyzed suicidal ideation in clinical samples,
      but only a few have been performed in the general population. We present the
      results of a two-stage epidemiological study in the general population on the
      island of Formentera (Balearic Islands, Spain), which used the 28-item General
      Health Questionnaire (GHQ-28) in the first stage (n = 697) and the Schedules for
      Clinical Assessment in Neuropsychiatry (SCAN) in the second (n = 242). We also
      recorded medical illnesses diagnosed in the subjects at the second stage. Four
      items on the GHQ-28 ask directly about suicidal thoughts or ideation. From the
      sample, 6.5% have reported suicidal ideation. Mental disorders are the most
      important factor associated with suicidal ideation; medical illnesses seem to
      play a secondary role.

PMID- 11459254
TI  - Differences in nonfatal suicide behaviors among Mexican and European American
      middle school children.
AB  - This report describes ethnic and gender differences in suicide ideation among two
      large samples of middle school students in New Mexico (n = 2,140) and Texas (n =
      1,302). Students completed a self-administered questionnaire on suicide ideation
      and psychosocial risk factors. Mexican Americans in both samples reported
      significantly higher prevalence of suicide ideation than did their European
      American counterparts. Mexican Americans were 1.8 times more likely to have high
      suicide ideation than European Americans. The suicide ideation risk for Mexican
      Americans remained unchanged in both samples after adjusting for gender, age,
      family structure, depression, low social support, and self-esteem. This study
      indicates that ethnicity plays an important role in suicidal ideation, but the
      mechanism remains unclear.

PMID- 11459255
TI  - Suicide in police--a critical review.
AB  - Police officers are commonly referred to as a high-risk group for suicide. So far
      no comprehensive review has been published about epidemiologic studies among
      police. This article systematically explores the worldwide literature on suicide
      in police. None of the recent nationwide studies show elevated suicide rates
      among police. Other studies show inconsistent results. Conclusively, it is not
      documented that there is an elevated suicide rate in police. A particular problem
      in previous research has been methodological shortcomings. There is need for
      further systematic research, and this review points out some strategies of
      research.

PMID- 11459256
TI  - Further comments on the nomenclature for suicide-related thoughts and behavior.

PMID- 11459257
TI  - Bone histomorphometry in celiac disease.
AB  - BACKGROUND AND AIMS: Bone metabolism in celiac patients is not well understood
      and there are no previous histomorphometric studies on bone of patients with
      celiac disease. The aim of the study was to investigate bone metabolism in celiac
      patients using bone histomorphometry, measurement of bone mineral density (BMD)
      and biochemical parameters. MATERIAL AND METHODS: The patient groups included 19
      men and 23 women with previously diagnosed celiac disease in remission (group I),
      7 women not in remission (group II) and 19 women and 9 men with newly diagnosed
      celiac disease (group III). Static and dynamic parameters of bone structure,
      formation and resorption were measured using undecalcified sections. The
      following parameters were obtained: bone volume (BV/TV; %), osteoid volume
      (OV/BV; %), osteoid surface (OS/BS; %), resoprtion surface (ES/BS; %), osteoid
      thickness(Oth; microm), mineral apposition rate (MAR; microm/day), and
      mineralization lag time (MinLag; day). BMD was measured at the spine (L2-4) and
      left femoral neck, trochanter and Ward's triangle. Serum calcium (S-Ca; mmol/L),
      alkaline phosphatase (AP; U/L), intact parathyroid hormone (S-PTH; ng/L), 25
      hydroxyvitamin D (S-25(OH)D; nmol/L), cross-linked carboxyterminal telopeptide of
      human type I collagen (S-ICTP; microg/L) and C-terminal extension peptide of type
      I procollagen (S-PICP; microg/L) were analysed. RESULTS: In the histomorphometric
      analysis there were no significant differences in static or dynamic parameters
      between the groups. Very low bone mass (< 10%) was found in one patient in every
      group. OV/BV was increased (> 3.5%) in all groups (31% in group I, 13% in group
      II and 29% in group III). OS/BS was increased (> 36.5%) in groups I and III (17%
      and 29% respectively). In group II OS/BS was normal in all patients.
      Mineralization defect was found in four patients in group I and in two patients
      in group III with otherwise normal histomorphometric results. ES/BS was increased
      in three patients in group I and III and in one patient in group II. One female
      patient in group III had increased osteoid parameters, resorption surface, S-PTH
      and low concentration of vitamin D reflecting hyperparathyroid changes in bone. S
      PTH was increased (66-87 ng/L) in four patients in group III and one of these
      patients had hyperparathyroid histological changes in bone. CONCLUSIONS: Static
      and dynamic histomorphometry of iliac crest bone biopsy are useful tools to
      evaluate bone metabolism in celiac disease especially if hyperparathyroidism or
      mineralization defect are suspected. Hyperparathyroidism may be a problem in the
      patients before introducing gluten-free diet. Mineralization defect and
      osteomalacic changes are common later on irrespective of whether the patients are
      in remission or not.

PMID- 11459258
TI  - Duration of thrombosis prophylaxis in orthopaedic surgery.
AB  - BACKGROUND: We have given seven to 14 days thrombosis prophylaxis after
      orthopaedic surgery. Recently, six weeks prophylaxis has been recommended. We
      wished to evaluate the implications of prolonging prophylaxis. METHODS: We made a
      very thorough search of the hospital register of diagnoses and the registers of
      the departments of radiology and nuclear medicine and determined the number of
      detected thromboembolic complications during a five and a half-year period.
      RESULTS: We identified 91 cases (0.50%) with thromboembolism during the first six
      weeks after 18.368 orthopaedic operations: 1.4% after 836 total hip
      arthroplasties and 1.0% after 1.845 hip fractures. In these two groups 19
      thromboembolic complications were registered after the second postoperative week.
      If it had been possible to prevent all of them by prolonging prophylaxis to six
      weeks, each avoided thromboembolism would have cost around US $ 23.700 in
      additional drug costs alone. One hip fracture patient died from probable thrombo
      embolism during the second and one during the fourth postoperative week. No hip
      arthroplasty patients died from a probable thromboembolic complication during the
      third to sixth postoperative week. CONCLUSIONS: We conclude that the frequency of
      clinically detectable thrombo-embolism and fatal pulmonary embolus is so low
      during the third to sixth postoperative weeks that prophylaxis beyond two weeks
      is unwarranted.

PMID- 11459259
TI  - Alendronate influences bending force of femoral diaphysis after orchidectomy in
      rats.
AB  - BACKGROUND AND AIMS: We examined the effect of alendronate on bone following
      orchidectomy-induced osteoporosis. MATERIAL AND METHODS: Eighty male rats were
      used. Group I (C) served as the untreated control. In group II (ALN), alendronate
      was administered subcutaneously (18 microg/kg). In group III (ORC), rats were
      castrated only. In group IV (ORC+ALN), administration of alendronate (18
      microg/kg) was started immediately after castration, and in group V (ORC + ALN
      21) medication was started 21 days after castration. Alendronate was given twice
      a week for eight weeks in the treatment groups. Bone mineral density (BMD) of the
      proximal femur, ultimate bending forces of femoral diaphyses, ash weights of
      femurs (AWcc) and the calcium content (Ca) of femoral ash were determined.
      Histomorphometric analysis was performed on trabecular bone of proximal tibiae.
      RESULTS: BMD of the proximal femur was significantly decreased by orchidectomy
      compared with C and ALN. However, no statistical difference was observed between
      alendronate-treated groups (ORC + ALN and ORC + ALN-21) and the ORC group.
      Histologically, alendronate reduced the trabecular bone turnover. Ultimate
      bending force increased significantly in the ORC+ALN-21 group compared with group
      C, and had a good correlation with the cortical width of tibia (r = 0.53, p <
      0.001). Ash weight per bone volume (AWcc) was lowest in the ORC group, whilst
      alendronate maintained AWcc after orchidectomy. CONCLUSION: Alendronate increased
      the ultimate bending force of the femoral diaphysis after orchidectomy. On the
      other hand, ALN treatment was not able to maintain the BMD of the proximal femur
      at the pre-orchidectomy level. Our results suggest that the remodelling and
      modelling of bone may influence the response to ALN treatment.

PMID- 11459260
TI  - Computers in surgical education and the operating room.
AB  - Medicine has gone through major changes over the last 50 years. Today it is
      recognized that medical knowledge doubles every 6-8 years. It is also true that
      with the advent of many new medical procedures, surgeons must continue to learn
      new techniques throughout their careers; this was not the case in the past.
      Significant changes have also occurred during the same period in computers. It
      has recently become apparent that there exists a synergy between these two
      industries - computers can be used to assist surgeons in both initial education
      and in learning new skills. The National Capital Area Medical Simulation Center
      is a unique resource that makes use of state-of-the-art computer resources to
      teach resuscitation and other skills. Both computerized mannequins and virtual
      reality training devices are used to teach surgical principles and technical
      procedures. The natural progression of this technology will be for virtual
      reality simulations to be used for selecting, training, certifying, and
      recertifying surgeons. Ultimately, surgeons will practice operative procedures
      using 3D data sets of the patients they plan to operate the next day and then use
      recordings to play back their optimal procedure robotically on their patients.

PMID- 11459261
TI  - Blood, sweat and tears.

PMID- 11459262
TI  - Blood substitutes in surgery.
AB  - BACKGROUND: Despite increasing safety of blood supplies, and blood conservation
      strategies, the need for blood transfusion is increasing. Due to storage
      characteristics, blood is not always available when it is needed. AIMS: Review
      the necessity for an oxygen carrying blood substitute. Review the history of the
      compounds that may become blood substitutes, and briefly describe those in
      clinical trials. MATERIAL AND METHODS: Review of literature in the area of blood
      substitutes. RESULTS AND CONCLUSIONS: There is a need for oxygen carrying blood
      substitutes. Despite disappointments in recent clinical trials leading to
      withdraw of some compounds, there are several promising products nearing clinical
      approval.

PMID- 11459263
TI  - Bioabsorbable implants in the fixation of fractures.

PMID- 11459264
TI  - Endovascular surgery for chronic limb ischaemia. Factors predicting immediate
      outcome on the basis of a nationwide vascular registry.
AB  - PURPOSE: To evaluate the early results of endovascular treatment of chronic limb
      ischemia and the factors influencing outcome. METHODS: The 5,575 endovascular
      procedures entered into the national vascular registry in 1991-1994 were reviewed
      retrospectively. Indication was claudication in 3,873 and chronic critical
      ischemia (CLI) in 1,702 procedures. In CLI most patients were women and older,
      with a higher proportion of diabetes mellitus, renal insufficiency and coronary
      heart disease than in claudication group although the incidence of smoking and
      hyperlipidaemia was lower. 60.2% of the procedures were performed in
      femoropopliteal arteries, 24.9% in iliac arteries and 14.9% in infrapopliteal
      arteries. The follow-up was 30 days. RESULTS: In the claudication group there was
      clinical improvement in 2,719 (82.8%) and in the CLI group in 851 (70.9%) of
      patients. Patency was better in the claudication than in CLI group, 94.6% vs.
      89.0% respectively. There was hemodynamic improvement, i.e. improvement of the
      ankle-brachial index of more than 0.15 in 1,680 (58.2%) patients with
      claudication and in 437 (59.7%) with CLI. In a logistic regression model diabetes
      mellitus and renal insufficiency increased the relative risk of amputations and
      mortality in CLI group, whereas, incidence of amputations was lower in patients
      with hyperlipidaemia. In claudication group femoropopliteal arteries had an
      adverse effect on patency. CONCLUSION: The clinical characteristics of the groups
      may explain some of the outcome differences. Angioplasty is recommended to be
      used in the femoropopliteal arteries if the symptoms are severe and in CLI group
      with diabetes and renal failure only in selected cases.

PMID- 11459265
TI  - Results of infrainguinal bypass surgery: an analysis of 263 consecutive
      operations.
AB  - BACKGROUND AND AIMS: The purpose of this clinical study was to assess the success
      of infrainguinal revascularization in the treatment of lower limb ischaemia.
      MATERIAL AND METHODS: 226 consecutive patients underwent 263 femoropopliteal (n =
      194) or femorodistal (n = 69) bypass operations during 1988-1996 at a university
      hospital. Records of all patients were reviewed. Late control visits including
      clinical and colour doppler ultrasound examinations were programmed for 109
      patients. Initial success, primary and secondary patencies, limb salvage and
      survival rates were determined and factors affecting outcome were analysed in
      various patient categories. RESULTS: Initial success rate was 92% (243/263). The
      primary and secondary patencies were 70/83% and 52/63% at one and five years,
      respectively. The corresponding limb salvage rates for patients with chronic
      critical ischaemia were 82% and 77%. The number of diseased vessels in the
      treated limb correlated negatively with the primary patency. Advanced age did not
      affect primary patency or limb salvage rates. Diabetes and the use of distal
      revascularizations were independent predictors of poorer limb salvage. Diabetes
      and renal insufficiency proved to shorten life expectancy. CONCLUSIONS:
      Infrainguinal revascularizations are effective regardless of patient's age. The
      extent of atherosclerotic changes in the operated limb, diabetes and renal
      insufficiency are factors affecting outcome.

PMID- 11459266
TI  - Cystic tumors of the pancreas: the radiologist.
AB  - In this article, the author reviews the effect of contemporary imaging techniques
      on the diagnosis of various pancreatic neoplasms. Histologic detail and the
      relationship to other means of diagnosis are included.

PMID- 11459267
TI  - Cystic neoplasms of the pancreas: benign to malignant epithelial neoplasms.
AB  - Clinical presentation and state-of-the-art imaging permit the differentiation of
      most cystic pancreatic neoplasms not only from other cystic pancreatic disorders
      but also from one another. The differentiation of serous cystic lesions from the
      mucinous neoplasms (cystadenoma or carcinoma and IPMT) is crucial because of the
      radically different biological characteristics of these two neoplasms. Although
      mucinous cystic neoplasms should be resected because of their premalignant or
      overtly malignant tendency, most patients with serous neoplasms require no
      operative intervention unless they are symptomatic. IPMT is best treated by a
      total pancreatectomy, although lesser subtotal resections should be strongly
      considered depending on patient age, medical comorbidity, and psychosocial
      situations.

PMID- 11459268
TI  - The surgical management of pancreatic neuroendocrine tumors.
AB  - NETs of pancreas are rare and may or may not be associated with symptoms of
      hormone overproduction. Treatment is required for control of tumor growth and for
      relief of symptoms associated with excess hormone. With advances in the
      nonsurgical management of many hormone-related symptoms (e.g., proton pump
      inhibitors or somatostatin analogues), care for many of these patients has
      shifted toward the control of tumor progression. Complete surgical resection is
      the only curative treatment for these tumors. With improvements in the
      preoperative imaging and intraoperative localization techniques, it is hoped that
      these tumors will be identified and resected for cure with increased frequency.
      For patients with hepatic metastasis, initial expectant observation and medical
      management of symptoms is appropriate in view of the long and indolent course of
      the disease. Hepatic arterial embolization is the preferred mode of palliation
      for pain and hormonal symptoms. A curative hepatic resection may be possible in
      selected patients.

PMID- 11459269
TI  - Islet cell tumors of the pancreas: the medical oncologist's perspective.
AB  - Islet cell tumors of the pancreas are rare, indolent, neuroendocrine tumors.
      Approximately 50% of the patients diagnosed with these tumors present with
      symptoms related to various biologically active hormones that are secreted by
      these neoplasms. Currently, the only curative treatment for islet cell tumors is
      complete surgical resection. Management of metastatic disease is conservative.
      Initial treatment of these tumors includes expectant observation and medical
      management of symptoms with clinical monitoring and serial CT scans to assess
      tumor growth. Patients with rapidly progressive disease, with local symptoms
      caused by tumor bulk, or with uncontrolled symptoms related to hormone secretion
      require more aggressive medical or surgical intervention. The somatostatin
      analogue octreotide may help control hormone secretion and stabilize tumor
      growth. Patients refractory to octreotide with tumor predominantly in the liver
      are potential candidates for mechanical ablative techniques, such as hepatic
      arterial embolization. Radiofrequency ablation and cryosurgical techniques may
      also be useful, although specific data are limited. Surgical resection of
      metastatic disease may offer palliative relief of symptoms related to hormone
      secretion in carefully selected patients. Chemotherapy may be used for palliation
      when ablative techniques have failed or when significant extrahepatic disease is
      present. Streptozicin-based combinations remain the first line standard, but
      major objective responses are less common than had been previously thought.
      Because of the overall modest success of current chemotherapeutic regimens,
      patients with advanced disease in need of treatment should be encouraged to
      enroll in clinical trials testing newer antineoplastic agents or newer treatment
      strategies.

PMID- 11459270
TI  - Periampullary cancers: are there differences?
AB  - Our review supports the clinical impression that periampullary cancers vary in
      outcome after resection. Overall survival after pancreaticoduodenectomy is
      greatest for patients with ampullary and duodenal cancers, intermediate for
      patients with bile duct cancer, and least for patients with pancreatic cancer.
      Moreover, survival for each tumor stage is greater for nonpancreatic
      periampullary cancers than for pancreatic cancers. Invasion of the pancreas by
      nonpancreatic periampullary cancers is a major factor adversely affecting
      survival. Recent data suggest that inherent differences in tumor biology rather
      than embryologic, anatomic, or histologic factors probably account for these
      differences in survival. Finally, although pancreaticoduodenectomy remains the
      procedure of choice for resectable periampullary cancers, further increases in
      survival will likely evolve through more effective neoadjuvant or adjuvant
      therapies rather than modifications in the surgical approach.

PMID- 11459271
TI  - Pancreatic cancer: the bigger picture.
AB  - Despite accurate diagnosis, better radiologic techniques, and safer surgery, long
      term survival after surgical therapy for pancreatic cancer is disappointing.
      Median survival following pancreaticoduodenal resection is 12 to 15 months
      independent of surgical expertise, hospital size, or technical factors. Subsets
      of favorable tumors and longer survival times after surgery have been defined and
      include: small tumor size and low-grade lesions, tumor-free margins, and absence
      of nodal, venous, or perineural invasion; however, long-term survivors of
      pancreatic cancer may have none of these favorable features, and their tumors
      commonly manifest the most adverse tumor prognostic features. The converse that
      small-sized, histologically favorable tumors result in long-term survivors, also
      is not true. Five-year survival rates average 5% or less after all resections. In
      a large series in which 118 pancreatic resections were performed in 684 evaluated
      patients over a 6-year period, there were 12 5-year survivors, 5 of whom died in
      the sixth year. A report of 10-year survivors after surgery numbered 13 patients.
      The best actual 5-year survival rate was reported by Trede et al. Of the 37, 5
      year survivors from a cohort of 118 patients, more than half died of cancer. This
      far exceeds any other actual survival rate and may be explained by a smaller
      tumor size. Farnell et al reported a 5-year survival rate difference (i.e.,
      actuarial survival) in a subset of 174 resected patients with adenocarcinoma
      without perineural or duodenal invasion and with negative nodes (23% versus
      6.8%), respectively. An impressive, large series of 616 patients with resected
      adenocarcinoma of the pancreas who underwent PDR (85%), distal pancreatectomy
      (9%), and total pancreatectomy (6%), has been reported. The mortality rate was
      2.1%, and postoperative complications occurred in 30%. The five-year survival
      rate was 15%. The author's best result was observed among 20 initially
      "unresectable" patients who were treated with chemoradiation therapy, followed by
      tumor extirpation. Among the 18 surgical survivors there are seven five-year
      survivors, three of whom are in their tenth year of survival. They are discussed
      in the article by Cooperman et al ("Long-term Follow-up...") elsewhere in this
      issue.

PMID- 11459272
TI  - Preoperative cardiac assessment of the candidate for major resective pancreatic
      surgery.
AB  - The risk of perioperative cardiac morbidity and mortality can be predicted based
      on clinical assessment and noninvasive testing for the detection of myocardial
      ischemia. Appropriate preoperative interventions in high-risk patients are
      indicated. Medical intervention with beta blockade is particularly effective.

PMID- 11459273
TI  - Pancreaticoduodenal resection: pearls, perils, and pitfalls.
AB  - The author provides a detailed account of pancreaticoduodenal resection,
      beginning with the selection among candidates for surgery. Abundant illustrations
      accompany the step-by-step directions. Conceivable complications are discussed.

PMID- 11459274
TI  - Personal observations, opinions, and approaches to cancer of the pancreas and the
      periampullary area.
AB  - This article reviews the diagnosis, staging, surgical, and adjuvant treatment of
      pancreatic and periampullary cancer based on personal experience covering 25
      years. In spite of remarkable progress, especially in regard to staging and
      surgical treatment, the authors conclude that with the modalities currently
      available, timely diagnosis and definitive cure of this particular cancer is
      rare.

PMID- 11459275
TI  - The Mayo clinic approach to the surgical treatment of adenocarcinoma of the
      pancreas.
AB  - Ductal carcinoma of the pancreas remains a challenging problem for
      gastrointestinal surgeons. Significant progress has been made in diagnosis,
      preoperative staging, and safety of surgery; however, long-term survival after
      resection is unusual, and cure is rare. That said, the authors maintain their
      aggressive posture regarding this disease, recognizing that resection offers the
      only potential for cure. The authors' approach such patients in the most
      efficient and least invasive manner possible, relying primarily on triple phase
      helical abdominal CT for clinical diagnosis and staging, reserving ERCP and EUS
      for diagnostic dilemmas. In fit candidates with potentially resectable lesions,
      the authors eschew pre- or intraoperative biopsy, angiography, or endoscopic
      stenting and use preliminary limited staging laparoscopy selectively. Surgical
      palliation is chosen for fit patients who, at exploration for potentially
      curative resection, are found to have occult distant metastases or locally
      unresectable disease. Radical pancreatoduodenectomy can be performed with a
      mortality rate of 3% or less, and although morbidity remains significant, most
      can be managed with conservative measures. Quality of life after
      pancreatoduodenectomy is good and, if not, is generally a manifestation of
      recurrence rather than physiologic alterations inherent to the procedure.
      Adjuvant chemoradiation is standard therapy after resection, recommended for
      those with locally unresectable disease but used selectively for those with
      distant metastasis. Survival after potentially curative resection has remained
      disappointing. Whether extended lymphadenectomy or neoadjuvant chemoradiation
      improves survival has not been determined. Clearly, methods for earlier diagnosis
      of pancreatic cancer and more effective adjuvant therapies are sorely needed.

PMID- 11459276
TI  - Opinions and commentary on treating pancreatic cancer.
AB  - Over the past 2 decades, major progress has been made in the perioperative and
      surgical management of pancreatic cancer. These advances have resulted in
      improved long-term results after surgical resection for pancreatic cancer. There
      are still many controversies surrounding the optimal management of this disease,
      however, resulting in wide variations in perioperative and operative care at
      different centers.

PMID- 11459277
TI  - Postoperative care of the pancreatic surgical patient: the role of the
      intensivist.
AB  - Improved patient selection and intraoperative techniques have reduced the need
      for an intensivist in the care of the pancreaticoduodenectomy patient.
      Perioperative hemodynamic fine-tuning and the precise management of postoperative
      complications, however, are areas in which an intensivist can offer expert help.
      An approach to hemodynamic management and the use of mechanical ventilation is
      offered. Meticulous detail in each organ system is stressed.

PMID- 11459278
TI  - The role of the infectious disease specialist in pancreatic surgery.
AB  - The author provides a concise account of postoperative complications of
      pancreatic surgery. Factors such as predisposition to morbidity, diagnostic
      detection, and treatment options are discussed.

PMID- 11459279
TI  - Palliative strategies for locally advanced unresectable and metastatic pancreatic
      cancer.
AB  - Technical improvement in perioperative morbidity and mortality with improved long
      term survival associated with pancreaticoduodenectomy for patients with
      pancreatic carcinoma has clearly established a role for this operation when
      performed with curative intent. Most patients with pancreatic adenocarcinoma will
      not be candidates for surgical resection of their disease. These patients will
      experience significant symptoms potentially requiring surgical and nonsurgical
      palliative interventions to treat unrelieved cancer-associated pain, obstructive
      jaundice, or the development of GOO. The primary goal for palliative
      interventions should be to relieve symptoms with minimal morbidity and to
      maintain or improve the quality of life for patients with an expected limited
      survival.

PMID- 11459280
TI  - Adjuvant therapy for pancreatic cancer: current treatment approaches and future
      challenges.
AB  - The past several decades have witnessed advances in the management of pancreatic
      cancer; however, much remains to be accomplished. Emerging techniques in the
      fields of surgery, RT, chemotherapy, and immunotherapy offer hope for greater
      locoregional control, survival, and quality of life for these patients.

PMID- 11459281
TI  - Treatment of metastatic pancreatic adenocarcinoma: a comprehensive review.
AB  - The current standard therapy for metastatic pancreatic adenocarcinoma is the
      single-agent gemcitabine, by the increasingly used fixed rate infusion of 10
      mg/m2/min. There is strong reason to anticipate that additional benefits will
      accrue with gemcitabine-based combination chemotherapy. Gemcitabine and CPT-11
      are synergistic with many drugs and non-cross-resistant with each other. Rigorous
      clinical investigations will be performed in an effort to identify optimal drug
      sequence and schedules for these novel combinations.

PMID- 11459282
TI  - Therapy for regionally unresectable pancreatic cancer.
AB  - Chemoradiotherapy for unresectable LAPA is associated with a median survival time
      of 9 months or more and manageable toxic side effects. Experience with RT-FSP
      provides evidence that chemoradiotherapy may extend survival time with or without
      resection. Chemoradiotherapy or entry into clinical trials is the standard for
      LAPA. The next generation of clinical trials for LAPA will incorporate newer
      agents, such as gemcitabine and irinotecan into chemoradiotherapy regimens. Novel
      agents, such as matrix-metaloproteinase inhibitors, transcription factor
      inhibitors, antiangiogenic factors, cyclooxegenase-2 inhibitors, and agents that
      target the K-ras point mutations associated with 90% of pancreatic cancers, are
      in early phases or clinical development and may have activity for micrometastic
      or minimal residual disease. Lower toxicity makes these drugs attractive agents
      for maintenance therapies. The multitude of new agents provides hope to patients
      and a welcome challenge for further investigation.

PMID- 11459283
TI  - Long-term follow-up of twenty patients with adenocarcinoma of the pancreas:
      resection following combined modality therapy.
AB  - Long-term follow-up of 5 or more years in 20 patients with initially unresectable
      cancer of the pancreas that responded to chemoradiation therapy is detailed in
      this article. All patients underwent resection. Seven or 18 surgical survivors
      are alive 50 or more months.

PMID- 11459284
TI  - Preoperative chemoradiation therapy for pancreatic cancer.
AB  - The authors present a critique of a fellow surgeon's version of multimodality
      therapy for patients with adenocarcinoma of the pancreas. Citing follow-up
      studies, the authors prescribe adjustments in therapeutic specifics to foster a
      more efficient approach to patients that results in lower toxicity and shorter
      treatment periods.

PMID- 11459285
TI  - Innovative treatments for pancreatic cancer.
AB  - Pancreatic cancer is the fifth leading cause of cancer deaths in the United
      States with little or no impact from conventional treatment options. Significant
      advances in understanding basic immunology have renewed interest in using
      immunotherapy to treat pancreatic cancer. Cancer immunotherapy, including
      humanized MAbs, cytokines, and potent vaccine strategies, has been successful in
      animal models and is being evaluated in clinical trials. Gene therapy is also
      being explored using methods to inactivate oncogenes, replace defective tumor
      suppressor genes, confer enhanced chemosensitivity to tumor cells, and increase
      immunogenicity of tumor cells. Angiogenesis, an essential step in the growth and
      metastasis of pancreatic cancer, has been targeted by many antiangiogenic agents.
      Several clinical trials have been initiated to evaluate the role of these
      innovative strategies in patients with pancreatic cancer with increasingly
      sophisticated correlative studies to learn more about the mechanisms of tumor
      rejection with these agents. The rapid translation of basic science discoveries
      to clinical trials should result in the development of new effective treatments
      for patients with pancreatic cancer.

PMID- 11459286
TI  - Increased matrix metalloproteinase 2 concentration and transcript expression in
      advanced colorectal carcinomas.
AB  - Colorectal cancer is one of the most common malignant tumors and entails a
      relatively poor prognosis. Clinical outcome depends on the extent of local and
      metastatic tumor spread. Results of in vivo and in vitro studies suggest that the
      balance between matrix metalloproteinases (MMPs) and their inhibitors (tissue
      inhibitors of metalloproteinases TIMPs) is altered in neoplasia, contributing to
      the invasive and metastatic properties of malignant tumors. We quantified tissue
      concentrations of MMP-2 and TIMP-2 in 65 malignant colorectal lesions and
      corresponding normal mucosa by enzyme-linked immunosorbent assay, western
      blotting, and in situ hybridization. In situ hybridization and western blot
      analyses demonstrated a clear increase in both stromal expression of MMP-2
      transcripts and protein in primary carcinomas. The protein concentration of MMP-2
      was higher in all tumor stages, except stage I tumors, than in normal mucosa and
      adenomas. MMP-2 concentrations were not related to tumor differentiation or to
      colonic versus rectal location. Surprisingly, the MMP-2 concentration was not
      increased in metastases. Interestingly, tissue concentrations and epithelial mRNA
      expression of TIMP-2 decreased significantly in primary colorectal cancer (UICC
      stages III and IV) but increased in metastases. Therefore an increased ratio of
      MMP-2 to TIMP-2 is strongly associated with advanced tumor stages, but a
      decreased ratio was observed in metastases. These findings suggest that the MMP
      2:TIMP-2 ratio may prove useful as a marker of local invasion but not of
      metastasis in colorectal cancer.

PMID- 11459287
TI  - Detection of cytokeratin 19 and 20 mRNA in peripheral and mesenteric blood from
      colorectal cancer patients and their prognosis.
AB  - To detect the presence of cancer cells in peripheral and mesenteric blood and to
      examine their relationship to prognosis in colorectal cancer patients undergoing
      curative surgery, we examined cytokeratin 19 and 20 mRNA in peripheral and
      mesenteric venous blood. Using reverse transcriptase polymerase chain reaction,
      cytokeratin 19 and 20 mRNA was amplified in peripheral and mesenteric blood
      samples obtained from 35 colorectal cancer patients who underwent curative
      surgery. Cytokeratin 19 or 20 mRNA in peripheral or mesenteric blood samples was
      detected in 18 of 35 cases (51%). There was no significant difference in Dukes'
      staging between the positive and negative groups. The median follow-up period was
      56 months. In the positive group six patients (33%) showed recurrences. One
      patient (6%) showed recurrence in the negative group. The recurrence rate was
      significantly higher in the positive group than in the negative group. Five-year
      disease-free survival was significantly better in the negative group than in the
      positive group (94% vs. 65%). The detection of cytokeratin 19 or 20 mRNA in
      peripheral or mesenteric blood is thus associated with the prognosis for
      colorectal cancer patients undergoing curative surgery. Although the presence of
      these mRNAs in blood samples is a prognostic marker, the clinical utility of this
      assay is questionable because of the low recurrence rate in the positive group.

PMID- 11459288
TI  - Leukocyte-depletion of blood components does not significantly reduce the risk of
      infectious complications. Results of a double-blinded, randomized study.
AB  - Allogeneic blood transfusions are claimed to be an independent risk factor for
      postoperative infections in open colorectal surgery due to immunomodulation.
      Leukocyte-depletion of erythrocyte suspensions has been shown in some open
      randomized studies to reduce the rate of postoperative infection to levels
      observed in nontransfused patients. Using a double-blinded, randomized design, we
      studied the postoperative infection rate in patients undergoing open colorectal
      surgery transfused with either leukocyte-depleted erythrocyte suspensions (LD
      SAGM) or non-leukocyte-depleted erythrocyte suspensions (SAGM). Unselected
      patients (n 279) were allocated to receive LD-SAGM (n 139) or SAGM (n 140) if
      transfusion was indicated. Forty-five percent were transfused, yielding 48
      patients in the LD-SAGM group and 64 in the SAGM group. Thirteen patients were
      excluded because they received one type of transfusion in spite of randomization
      to the other type. No significant differences in the rates of postoperative
      infections (P=0.5250) or postoperative complications (P=0.1779) were seen between
      the two transfused groups. Infection rates were 45% and 38% in the transfused
      groups and 21% and 23% in the nontransfused groups. No significant difference
      between the transfused groups was seen on any single infectious event, mortality
      rate, or duration of hospitalization. Leukocyte-depletion of erythrocyte
      suspensions transfused to patients undergoing open colorectal surgery does not
      reduce postoperative infection rates.

PMID- 11459289
TI  - Growth inhibition and apoptosis induced by P2Y2 receptors in human colorectal
      carcinoma cells: involvement of intracellular calcium and cyclic adenosine
      monophosphate.
AB  - Extracellular nucleotides induce apoptosis and inhibit growth of colorectal
      cancer cells. To understand the underlying signaling pathways, we investigated
      the role of nucleotide-sensitive P2 receptors and focused on the receptor
      mediated signaling of intracellular Ca2+ and cyclic adenosine monophosphate
      (cAMP) in two colorectal carcinoma cell lines (HT29, Colo320 DM). Expression and
      functionality of P2 receptor subtypes evaluated by RT-PCR and [Ca2+]i imaging
      revealed that solely metabotropic P2 receptors of the subtype P2Y2 were expressed
      on a functional level in both cell lines. Short-term stimulation of P2Y2
      receptors caused Ca2+ mobilization from intracellular stores and a subsequent
      transmembrane Ca2+ influx. The receptor-induced [Ca2+]i elevation was shown to
      increase basal-stimulated [cAMP]i moderately and to potentiate forskolin
      stimulated [cAMP]i vigorously, since the effects were dose-dependently inhibited
      by preloading the cells with the [Ca2+]i chelator BAPTA. In contrast, activation
      of protein kinase C (PKC) did not contribute to a receptor-mediated rise in
      [cAMP]i, since the PKC inhibitor staurosporine completely failed to reduce P2Y2
      receptor-induced increases in [cAMP]i. Prolonged application of P2Y2 receptor
      agonists induced a time-dependent increase in apoptosis (up to 50% above control
      values) in both cell lines and caused dose-dependent inhibition of cell
      proliferation of up to 85% (Colo320 DM) or 64% (HT29). Chelating [Ca2+]i with
      BAPTA almost completely abolished P2Y2 receptor-induced cell death. Rises in
      [cAMP]i elicited by either forskolin or cAMP derivatives inhibited growth in both
      cell lines, too. In line with the potentiating effect of P2Y2 receptors on
      forskolin-stimulated [cAMP]i increases, costimulation with forskolin and P2Y2
      receptor agonists led to synergistic antiproliferative effects. Moreover, a
      synergistic growth inhibition was observed when coincubating the cells with the
      P2Y2 receptor agonist ATP and the cytostatic drug 5-fluorouracil, which forms the
      basis for most currently applied chemotherapeutic regimes in colorectal cancer
      treatment. Our results demonstrate the growth inhibitory potency of P2Y2
      receptors in colorectal carcinoma cells. Receptor-induced [Ca2+]i signaling
      appears to play a major role in the observed antiproliferative and apoptosis
      inducing effects.

PMID- 11459290
TI  - Prolonged activation of mitogen-activated protein kinases during NSAID-induced
      apoptosis in HT-29 colon cancer cells.
AB  - The mechanisms of the antineoplastic effect of nonsteroidal anti-inflammatory
      drugs (NSAIDs) still are unknown, but the induction of apoptosis is one of the
      possible mechanisms. We attempted to demonstrate the role of mitogen-activated
      protein (MAP) kinases, generally considered to be important mediators of
      proliferative and apoptotic signals, in NSAID-induced colon cancer cell
      apoptosis. Apoptosis was detected by demonstration of DNA fragmentation in
      agarose gel electrophoresis. Cell death was assessed by trypan blue dye exclusion
      method. MAP kinase activation was assessed by Western blot using phosphospecific
      antibodies to MAP kinases. Kinase assay using activating transcription factor-2
      (ATF-2) fusion protein as a substrate was also performed for measuring p38 MAP
      kinase activity. For the inhibition of p38 MAP kinase, pyridinylimidazole
      compound (SB203580) was utilized. Caspase-3 activity was measured using the
      tetrapeptide fluorogenic substrate Ac-DEVD-AMC. Treatment of HT-29 cells with
      NSAIDs results in time- and dose-dependent induction of apoptosis, accompanied by
      sustained activation of all three MAP kinase subfamilies. The SB203580, a p38 MAP
      kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059,
      a MAPK/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and
      caspase-3 activation were not significantly interlinked in indomethacin-induced
      apoptosis. From these results, we conclude that NSAIDs can induce prolonged
      activation of MAP kinases in colon cancer cells and that, of these, p38 MAP
      kinase may play a partial but significant role in indomethacin-induced apoptosis.

PMID- 11459291
TI  - Efficacy of use of colonoscopy in dextran sulfate sodium induced ulcerative
      colitis in rats: the evaluation of the effects of antioxidant by colonoscopy.
AB  - The goals in developing animal models of inflammatory bowel disease (IBD) are to
      determine the underlying mechanisms and the action of currently available drugs
      and to evaluate the value of new therapeutic approaches. Because of the
      difficulty in determining the severity of colitis in living animals, it has been
      necessary to kill the experimental animals at varying stages in the studies. If
      colonoscopic evaluation or endoscopic biopsy is feasible in these experimental
      animals, continuous observations could be possible, thus avoiding the need to
      kill them. The aims of the current study were to assess the efficacy of
      endoscopic examination as a monitoring tool for the severity of colitis in rats
      and to the efficacy of DA-9601, an extract from Artemisia asiatica which has both
      antioxidative and cytoprotective actions, on dextran sulfate sodium induced
      ulcerative colitis in rats endoscopically. Sprague-Dawley rats received 4% DSS in
      drinking water for 5 consecutive days. Either DA-9601 or sulfasalazine was
      administered twice a day for 8 days, starting 3 days before DSS administration.
      After the colonoscopic evaluations on days 2, 4, and 5 after DSS administration
      the rats were also killed for gross and histopathological evaluations.
      Simultaneous measurements of malondialdehyde (MDA) and myeloperoxidase (MPO)
      activities were performed. There was a statistically significant correlation
      between the scores evaluated by the gross examination and colonoscopic scores,
      between the colonoscopic scores and the levels of MDA or mucosal MPO activities,
      and between colonoscopic scores and histopathological activity index. DA-9601
      showed excellent improvement in gross lesion scores, decreased MDA amounts and
      MPO activities compared to sulfasalazine. In conclusion, the introduction of
      appropriate colonoscopic examination in animal models of IBD could avoid the
      sacrifice of experimental animals for interim evaluation and provide the valuable
      information on the course and efficacy of treatment. The potential usefulness of
      antioxidants in treating IBD is very promising based on the colonoscopic
      intervention of IBD.

PMID- 11459292
TI  - Does loperamide affect motor activity after proctocolectomy and ileal pouch-anal
      anastomosis? An experimental study in dogs.
AB  - This study investigated the effect of loperamide on the motor function of small
      intestine and J-pouch. Proctocolectomy and ileal pouch-anal anastomosis were
      performed in four dogs. Motility was recorded by serosal electrodes and strain
      gauge transducers. The intestinal transit time was determined radiologically.
      Multiple measurements were performed before and during chronic administration of
      loperamide. This treatment led to a significant decrease in median stool
      frequency from 11 (10-13) to 9 stools/day (8-12) and a tendential increase in
      intestinal transit time from 60 (50-105) to 70 min (60-90). This was not
      accompanied by significant changes in fasted or postprandial motility. There were
      no significant differences in the characteristics of the migrating myoelectric
      complex or in the fed pattern, either in the small intestine or in the pouch.
      Loperamide thus does not significantly affect intestinal motility after ileal
      pouch-anal anastomosis. The reduction in stool frequency seems to be due to
      antisecretory effects in the first line.

PMID- 11459293
TI  - Breathhold unenhanced and gadolinium-enhanced magnetic resonance tomography and
      magnetic resonance cholangiography in hilar cholangiocarcinoma.
AB  - We assessed the imaging characteristics of hilar cholangiocarcinoma in magnetic
      resonance imaging (MRI) and magnetic resonance cholangiography (MRC). Breathhold
      MRI (T2-weighted turbo spin echo sequences, unenhanced T1-weighted gradient echo
      sequences, and gadolinium-enhanced fat-suppressed gradient echo sequences) and
      breathhold MRC (fat-suppressed two-dimensional projection images) performed in 12
      patients with histologically confirmed hilar cholangiocarcinoma were
      retrospectively reviewed for morphological tumor characteristics and contrast
      enhancement patterns. MRC demonstrated a significant bile duct stenosis with
      intrahepatic bile duct dilatation in all cases except in one patient who received
      an endoprothesis prior to imaging. Hilar cholangiocarcinoma was diagnosed by MRC
      only in one patient and MRI and MRC in 11. Mass lesions were seen in nine
      patients and circumferential tumor growth in three, including the patient
      diagnosed by MRC only. The tumor appeared hypointense relative to liver
      parenchyma in 10 of 11 patients in unenhanced T1-weighted images. T2-weighted
      sequences showed isointense or only slightly hyperintense signal in 5 of 11
      patients, 3 of whom demonstrated desmoplastic reactions by histology. The other 6
      patients revealed strongly hyperintense signal intensities. Contrast enhancement
      was increased compared to liver in 5 of 11 patients and decreased in 6 of 11
      patients. MRI with MRC seem to be a sensitive tools in the detection of hilar
      cholangiocarcinomas. The variable imaging characteristics are most probably
      related to the inhomogeneous histological appearance of this tumor entity.

PMID- 11459294
TI  - Solitary colonic metastasis from renal cell carcinoma 9 years after nephrectomy:
      report of a case.

PMID- 11459295
TI  - Supercritical fluid simulated moving bed chromatography II. Langmuir isotherm.
AB  - The simulated moving bed (SMB) technology offers the possibility of scaling up
      single column, batch chromatographic separations to continuous operation. This
      has proved particularly effective for the separation of enantiomers, and has been
      applied in the liquid and gas phase, as well as using a supercritical fluid as
      eluent (SF-SMB). In the last case, the main performance improvements are due to
      the possibility of tuning the elution strength of the mobile phase, by changing
      the pressure in the four sections of the SMB unit. Thus a SF-SMB can be operated
      in two modes, i.e. the isocratic and the pressure gradient mode. In this
      research, design criteria for these two operating modes have been developed,
      which can be applied to systems described by linear as well as nonlinear Langmuir
      adsorption isotherms. The role and effect of an appropriate modifier in
      increasing solubility and reducing retention times have been investigated. The
      results reported allow to identify the operating conditions, including the
      pressure levels and the modifier concentration, which lead to optimal separation
      performance in terms of productivity and desorbent requirement.

PMID- 11459296
TI  - Suppressed ion chromatography methods for the routine determination of ultra low
      level anions and cations in ice cores.
AB  - The concentration of trace ionic species in snow and ice samples was determined
      using suppressed ion chromatography (IC) with conductivity detection and ultra
      clean sample preparation techniques. Trace anion species were determined in a
      single 24-min run by combining sample preconcentration with gradient elution
      using Na2B4O7 eluent. The detection limits (ranging from 0.001 to 0.006 microM)
      are the lowest reported in the literature. Cation species were analysed by direct
      injection of 0.25 ml and isocratic elution with a H2SO4 eluent. The clean
      preparation techniques showed no evidence of a difference (Student's t-test)
      between Milli-Q water samples analysed directly and processed Milli-Q ice
      samples. These robust, ultra-clean IC methods were routinely applied to the
      analysis of large number of samples to produce a high-resolution trace ion ice
      core record from Law Dome, East Antarctica.

PMID- 11459297
TI  - Time-resolved cryogenic modulation reveals isomer interconversion profiles in
      dynamic chromatography.
AB  - The dynamic chromatographic study of interconversion of E and Z forms of oximes
      has been investigated by using a novel cryogenic modulation method in a two
      dimensional gas chromatographic array. The primary column is a conventional
      capillary GC column on which the molecular interconversion proceeds. In this
      case, the molecular dynamical process leads to a peak profile describing the
      kinetics and thermodynamics of the interconverting molecules during its
      chromatographic elution. Thus an interconversion region intercedes the elution of
      the individual stereoisomers of the reaction. Since the molecules are isomers,
      classical molecular identification methods such as gas chromatography-mass
      spectrometry are unable to study the individual instantaneous amounts of each of
      the compounds. Hence the infinitesimal profiles of interconversion along the
      entire column have never been experimentally observed; rather the total profile
      is normally subjected to mathematical modelling studies in order to match
      experiment with theory, and to gain the kinetic parameters of the process. In the
      present study, an instantaneous ratio of the individual isomers can be found
      during the chromatographic elution by direct measurement. This is achieved by
      using a cryogenic zone focussing process, with rapid longitudinal modulation of a
      cold trap and continual pulsing of collected zones into a fast-analysis high
      resolution capillary column on which isomer interconversion is minimized. The
      data can be displayed as a two-dimensional contour plot to demonstrate the
      individual isomer profiles. The two-dimensional analysis also allows easy
      measurement of the peak ratios of the two isomers which is an indicator of the
      extent of interconversion that has taken place. Two model systems, acetaldoxime
      and butyraldoxime, were chosen to illustrate the use of the cryogenic modulation
      procedure. It is anticipated that the procedure could be applied to other
      molecules which exhibit gas-phase isomerizations or reactions.

PMID- 11459298
TI  - Simple, non-moving modulation interface for comprehensive two-dimensional gas
      chromatography.
AB  - A simple, non-moving dual-stage CO2 jet modulator is described, which cools two
      short sections of the front end of the second-dimension column of a comprehensive
      two-dimensional gas chromatograph. A stream of expanding CO2 is sprayed directly
      onto this capillary column to trap small fractions eluting from the first
      dimension column. Remobilization of the trapped analytes is performed by direct
      heating by the GC oven air. Installation, maintenance and control of the
      modulator is simple. Focusing and remobilization of the fractions is a very
      efficient process, as the bandwidths of the re-injected pulses are less than 10
      ms. As a result, alkane peaks eluting from the second-dimension column have
      peakwidths at the baseline of only 120 ms.

PMID- 11459299
TI  - Polymer characterization by size-exclusion chromatography with multiple
      detection.
AB  - Size-exclusion chromatography with coupled multiangle light scattering and
      differential refractometry detectors has been used to obtain molecular mass and
      radius of gyration distributions of polydisperse polymer samples. From these data
      the scaling law between dimensions and the absolute molecular mass is obtained
      with just one sample of each polymer. Three different kinds of polymers are
      presented: polystyrene which serves as reference polymer, polyphosphazenes which
      behave abnormally in solution and poly(ethylene oxide) which is soluble in water.
      Since the relationship between dimensions and molecular mass depends on the
      extent of interactions between chain segments and solvent molecules, the scaling
      law provides information about the solution properties of the polymer.

PMID- 11459300
TI  - Capillary gas chromatography-atomic emission spectroscopy-mass spectrometry
      analysis of sulphur mustard and transformation products in a block recovered from
      the Baltic Sea.
AB  - A block of yperite fished up from the Baltic Sea was analysed by gas
      chromatography coupled with atomic emission spectrometry and mass spectrometry.
      In the samples of the block about 50 compounds were detected, out of which 30
      were identified. The identification of the compounds was performed by using the
      element chromatograms of the investigated compounds, and the data obtained by
      mass spectrometric detection. Thiodiglycol was not found among the compounds
      present in the investigated block. The calculations of the contents of sulphur
      mustard and some products in the block were performed by an external calibration
      method using bis(2-chloroethyl) sulphide as the standard. A satisfactory
      precision of elements determinations was obtained (RSD from 4.4 to 14.3%).

PMID- 11459301
TI  - Analysis of pesticide residues in wine by solid-phase extraction and gas
      chromatography with electron capture and nitrogen-phosphorus detection.
AB  - A feasible and reproducible method for multiresidue analysis of several common
      pesticides, of different polarities, in wine samples is proposed. The method
      combines a solid-phase extraction on polymeric cartridges eluted with ethyl
      acetate and a gas chromatographic determination using electron capture and
      nitrogen-phosphorus detection. To avoid the matrix effect, previous washing of
      the cartridges with a mixture of water-2-propanol (90:10) and further clean-up of
      the extract on Florisil cartridges, together with a calibration using spiked
      extracts, are recommended.

PMID- 11459302
TI  - Quantitative analysis and synthesis of the electrokinetic mass transport and
      adsorption mechanisms of a charged adsorbate in capillary electrochromatography
      systems employing charged adsorbent particles.
AB  - The dynamic mathematical model of Grimes and Liapis [J. Colloid Interf. Sci. 234
      (2001) 223] for capillary electrochromatography (CEC) systems operated under
      frontal chromatography conditions is extended to accommodate conditions in CEC
      systems where a positively charged analyte is introduced into a packed capillary
      column by a pulse injection (analytical mode of operation) in order to determine
      quantitatively the electroosmotic velocity, electrostatic potential and
      concentration profiles of the charged species in the double layer and in the
      electroneutral core region of the fluid in the interstitial channels for bulk
      flow in the packed chromatographic column as the adsorbate adsorbs onto the
      negatively charged fixed sites on the surface of the non-porous particles packed
      in the chromatographic column. Furthermore, certain key parameters are identified
      for both the frontal and analytical operational modes that characterize the
      performance of CEC systems. The results obtained from model simulations for CEC
      systems employing the analytical mode of operation indicate that: (a) for a given
      mobile liquid phase, the charged particles should have the smallest diameter,
      d(p), possible that still provides conditions for a plug-flow electroosmotic
      velocity field in the interstitial channels for bulk flow and a large negative
      surface charge density, deltao, in order to prevent overloading conditions; (b)
      sharp, highly resolute adsorption zones can be obtained when the value of the
      parameter gamma2min, which represents the ratio of the electroosmotic velocity of
      the mobile liquid phase under unretained conditions to the electrophoretic
      velocity of the anions (0>gamma2.min>-1), is very close to negative one, but the
      rate at which the solute band propagates through the column is slow; furthermore,
      as the solute band propagates across larger axial lengths, the desorption zone
      becomes more dispersed relative to the adsorption zone especially when the value
      of the parameter gamma2,max, which represents the ratio of the electroosmotic
      velocity of the mobile liquid phase under retained conditions to the
      electrophoretic velocity of the anions (0>gamma2,max>-1), is significantly
      greater than gamma2,min; (c) when the value of the equilibrium adsorption
      constant, K(A),3, is low, very sharp, highly resolved adsorption and desorption
      zones of the solute band can be obtained as well as fast rates of propagation of
      the solute band through the column; (d) sharp adsorption zones and fast
      propagation of the solute band can be obtained if the value of the mobility, v3,
      of the analyte is high and the value of the ratio v1/v3, where v1 represents the
      mobility of the cation, is low; however, if the magnitude of the mobility, v3, of
      the analyte is small, dispersed desorption zones are obtained with slower rates
      of propagation of the solute band through the column; (e) good separation of
      analyte molecules having similar mobilities and different adsorption affinities
      can be obtained in short operational times with a very small column length, L,
      and the resolution can be increased by providing values of gamma2,min and
      gamma2,max that are very close to negative one; and (f) the change in the
      magnitude of the axial current density, i(x), across the solute band could serve
      as a measurement for the rate of propagation of the solute band.

PMID- 11459303
TI  - Linear solvation energy relationships of mixed micelles of sodium dodecyl sulfate
      and decanol: towards a better model of octanol/water partitioning.
AB  - We show that we can alter the mechanism of micelle/water partitioning by the
      addition of decanol as a co-surfactant to an SDS micellar solution. Linear
      solvation energy relationship (LSER) studies indicate that as we increase the
      amount of decanol added to sodium dodecyl sulfate solution, the hydrogen bond
      donating ability of the aqueous phase increases and the cavity term of the
      micellar phase increases. We obtain a better correlation with octanol/water
      partitioning using the mixed micelle system compared to normal micelle solution.
      Choosing the appropriate micelle marker is very important. Significant changes in
      the LSER equations can occur if a different compound is used as the micelle
      marker.

PMID- 11459304
TI  - Use of vancomycin silica stationary phase in packed capillary
      electrochromatography. II. Enantiomer separation of venlafaxine and O
      desmethylvenlafaxine in human plasma.
AB  - A capillary electrochromatography method, using vancomycin chiral stationary
      phase packed capillary, was optimized for the simultaneous chiral separation of
      the antidepressant drug venlafaxine and its main active metabolite O
      desmethylvenlafaxine. Simultaneous baseline enantiomeric separation of the two
      compounds was obtained using a mobile phase composed of 100 mM ammonium acetate
      buffer pH 6/water/acetonitrile (5:5:90, v/v). The electrokinetic injection for
      sample introduction provided a limit of quantitation for both the compounds of
      0.05 microg/ml racemate concentration suitable for the analysis of venlafaxine
      and metabolite in biological samples. The acetonitrile mobile phase concentration
      was found to modulate the analytes elution times, the enantiomeric resolution and
      the efficiency of the separation. The column was tested for repeatability and
      linearity showing RSD values (%) in the range of 0.13-0.24, 2.47-3.66 and 1.35
      2.50 for migration time, sample/internal standard peak area ratio and
      enantiomeric resolution, respectively and correlation coefficients higher than
      0.9990. The method was applied to the analysis of clinical samples of patients
      under depression therapy showing a stereoselective metabolism for venlafaxine.

PMID- 11459305
TI  - Analysis of black tea theaflavins by non-aqueous capillary electrophoresis.
AB  - In this study a new capillary electrophoresis (CE) method was developed to
      quantify the four major theaflavins occurring in black tea. Where aqueous based
      CE methods showed poor selectivity and considerable band broadening, non-aqueous
      CE achieved baseline separation of the theaflavins within 10 min. The effects of
      the organic solvent composition and background electrolyte concentration on the
      separation selectivity and electrophoretic mobilities were investigated. Our
      optimized separation solution consisted of acetonitrile-methanol-acetic acid
      (71:25:4, v/v) and 90 mM ammonium acetate. This method was used to analyze three
      black tea samples.

PMID- 11459306
TI  - Demonstration of simultaneous cation-exchange and reversed-phase mechanisms on a
      strong-acid cation-exchange column.
AB  - It is demonstrated in this report that a conventional strong-acid cation-exchange
      column can exhibit reversed-phase chromatographic behavior simultaneously with
      ion-exchange. Adjusting the pH to control cation retention has no effect on the
      retention of neutral organic analytes. Likewise, changes in the methanol content
      of the mobile phase to adjust organic analyte retention causes only a small
      decrease in retention of metal ions in the 0 to 10% (v/v) methanol range, and no
      significant effect beyond that. Linear calibration behavior of both metal cations
      and neutral organic analytes is found on this column over three-order of
      magnitude. Examples of simultaneous metal cation-neutral organic separations in
      both the isocratic and gradient modes are shown, with conductivity detection for
      the metal ions and UV for the organic analytes. An isocratic separation of metal
      ions and neutrals in a vitamin pill is also demonstrated.

PMID- 11459307
TI  - Determination of fipronil by solid-phase microextraction and gas chromatography
      mass spectrometry.
AB  - A method for the determination of trace amounts of the insecticide fipronil was
      developed using solid-phase microextraction-gas chromatography-mass spectrometry
      and selected ion monitoring. Fipronil was extracted with a fused-silica fiber
      coated with 85 microm polyacrylate. The effects of pH, ionic strength, sample
      volume, extraction and desorption times as well as the extraction temperature
      were studied. Lindane was used as an internal standard. The linear concentration
      range of application was 0.3-100 ng ml(-1) of fipronil, with a relative standard
      deviation of 9.5% (for a level of 50 ng ml(-1)) and a detection limit of 0.08 ng
      ml(-1). The method was applied to check the eventual existence of fipronil above
      this limit in water and soil samples from Granada (Spain) as well as in human
      urine samples. The method validation was completed with spiked matrix samples.
      The method can be applied as a monitoring tool for water, soil and urine, in the
      investigation of environmental and occupational exposure to fipronil.

PMID- 11459308
TI  - Qualitative detection of selenium in fortified soil and water samples by a paper
      chromatographic-carboxyl esterase enzyme inhibition technique.
AB  - Thevetia peruviana seed carboxyl esterase was employed as a biosensor for the
      detection of selenium compounds by an enzyme inhibition technique on paper
      chromatograms. The selenium compounds (sodium selenite and selenium dioxide)
      appeared as white spots on a magenta background due to the inhibition of Thevetia
      peruviana seed carboxyl esterase (substrate 1-naphthyl acetate, coupling reagent
      Fast blue B salt). The minimum detectable amounts were about 5 microg of sodium
      selenite and 5 microg of selenium dioxide. Many other animal and plant carboxyl
      esterases gave no inhibition spot under the same conditions. Soil and water
      samples were fortified with sodium selenite and selenium dioxide. A procedure for
      preparing test solutions and conditions for paper chromatography was established.

PMID- 11459309
TI  - Ion-exchange chromatography by dicarboxyl cellulose gel.
AB  - A new column packing material for ion-exchange chromatography was prepared from
      cellulose gel by periodate oxidation followed by chlorite oxidation to form
      spatially paired carboxyl groups (dicarboxyl cellulose, DCC). The carboxyl group
      was quantitatively introduced to spherical cellulose gel by controlling the
      extent of oxidation. The DCC gels were examined for their ion-exchange activity
      for various amines at pH of 2.5-5.5. In this pH range, aromatic amines with acid
      dissociation constant (pKa) below 2.7 showed no interaction with DCC gels as
      expected from their lack of protonation. The amines with pKa greater than 3.3,
      both aromatic and aliphatic, showed strong interaction corresponding to the
      amount of carboxyl introduced to the gel. However, these amines showed anomalous
      dependence on pH of the mobile phase, showing a maximum in retention factor at
      around pH 4. This is in contrast with the nearly constant retention factor of
      these amines on conventional carboxylated cellulose packing at pH greater than
      4.0. The maximum retention factor at pH 4 of DCC gel was 4-5-times greater than
      that of conventional gel having a similar amount of carboxyls. Since pKa of
      dicarboxyl groups ranges 3-5 as determined by acid-base titration, the pH giving
      maximum retention corresponds to the pH at which one of paired carboxyls is
      dissociated. Possible cause of this anomaly is presented in terms of dissociation
      state of dicarboxyl groups and its interaction with amines.

PMID- 11459310
TI  - Comparison of chromatographic properties of cyanopropyl-, diol- and aminopropyl-
      polar-bonded stationary phases by the retention of model compounds in normal
      phase liquid chromatography systems.
AB  - Polar-bonded stationary phases, such as CN-, diol- and NH2-silica, have been
      characterised by the retention of model solutes (phenols, aromatic amines and
      quinoline bases) in normal-phase systems using n-heptane--polar modifier (2
      propanol, tetrahydrofuran or dioxane) mixtures as eluents. The selectivity of
      separation for the particular groups of substances has been analysed by the log
      kI versus log kII relationships for CN- and diol, CN- and NH2- and NH2- and diol
      phases in examined eluent systems by the plotting of correlation lines. The
      values of regression coefficient r indicate either the similarity of the
      retention mechanisms of model solutes in some examined systems where r>0.9, or
      differences among various systems where r<<0.9. The values of slopes of
      correlation lines show the selectivity of separation for particular group of
      compounds. The selectivity of separation has also been characterised by deltalog
      k values. The effect of modifier (2-propanol, tetrahydrofuran and dioxane) on
      selectivity of model solutes on these phases has also been discussed.

PMID- 11459311
TI  - On-line coupling of sol-gel-generated immunoaffinity columns with high
      performance liquid chromatography.
AB  - The paper demonstrates the possibility to use sol-gel-generated immunoaffinity
      columns as selective sample preparation step in on-line combination with HPLC. In
      the past sol-gel-generated immunoaffinity columns have only been included in off
      line sample preparation schemes. Compared with conventional RP-materials on-line
      coupling of sol-gel-generated silica matrices with a pore structure designed to
      retain antibodies poses additional problems caused by their lower pressure
      tolerance and by the necessity to match the mobile phases not only to take into
      account the chromatographic properties but also the conformational stability of
      the antibodies. These problems have been overcome by an on-line system which can
      be regarded as a prototype for similar systems which exploit the selectivity of
      sol-gel immunoaffinity columns. The system consists of a sol-gel-generated
      immunoaffinity column coupled to an RP enrichment column and an analytical
      column. The practicality of such systems is demonstrated using the example of
      anti-pyrene immunoaffinity columns applied for the determination of pyrene in
      aqueous solutions.

PMID- 11459312
TI  - On-line dialysis as a sample preparation technique for ion chromatography.
AB  - The use of on-line dialysis as a sample preparation technique for ion
      chromatography is described. A fully automated sample preparation device coupled
      to an ion chromatographic system for the determination of anions and cations in
      various matrices is presented. The method was based on stopped-flow dialysis,
      where the samples were continuously dialyzed for 10 min while the acceptor
      solution was stationary within the recipient channel. The matrices examined,
      without additional sample treatment, included milk, untreated wastewater, fruit
      juice, engine coolant, and a multivitamin tablet. The analyte recoveries for
      anions and cations in various matrices ranged from 87 to 106%. In addition,
      multiple sample injections were performed and repeatabilities were found in the
      range of 0.2 to 4%.

PMID- 11459313
TI  - Analysis of the band profiles of the enantiomers of phenylglycine in liquid
      chromatography on bonded teicoplanin columns using the stochastic theory of
      chromatography.
AB  - The retention behaviour of the enantiomers of underivatized phenylglycine was
      studied on a Chirobiotic T column packed with amphoteric glycopeptide teicoplanin
      covalently bonded to the surface of silica gel. The retention and the selectivity
      of separation of the enantiomers increase with rising concentration of ethanol or
      of methanol in aqueous-organic mobile phases. The band profiles of the less
      retained L-phenylglycine are symmetrical, but the band profiles of the more
      strongly retained D-phenylglycine are tailing in all mobile phases tested. The
      band broadening does not diminish even at very low concentrations of
      phenylglycine, so that it cannot be attributed to possible column overload. The
      analysis of the band profile using the stochastic theory of chromatography
      suggests that the broadening can be attributed to at least two additional chiral
      centres of adsorption in the stationary phase contributing to the retention of
      the more strongly retained enantiomer in addition to the adsorption of the less
      retained one. This behaviour can be explained by the complex structure of the
      teicoplanin chiral stationary phase.

PMID- 11459314
TI  - High-performance liquid chromatographic enantioseparation of bicyclic 1,3-amino
      alcohols.
AB  - Different high-performance liquid chromatographic methods were developed for the
      separation and identification of enantiomers of diendo- and diexo-3
      aminobicyclo[2.2.1]heptane-2-methanol and diendo- and diexo-3-amino
      bicyclo[2.2.1]hept-5-ene-2-methanol derivatives. Direct separation was carried
      out on a naphthylethyl carbamate-derivatized beta-cyclodextrin (Cyclobond I 2000
      SN) stationary phase, which was used in the polar-organic mode. This allowed the
      simultaneous separation of stereoisomers of alcohol and ester analogs of the
      bicyclic 1,3-amino alcohols. Alternatively, the derivatization of amino alcohols
      on the amino group with 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide produced
      diastereomers which were separable with high resolution (Rs>5-10) on a
      LiChrospher RP-18 stationary phase. The order of elution of the enantiomers was
      determined by both direct and indirect methods.

PMID- 11459315
TI  - Validation of a liquid chromatographic method for the determination of ranitidine
      hydrochloride residues on surfaces in the manufacture of pharmaceuticals.
AB  - A liquid chromatographic method for determination of the residues of ranitidine
      hydrochloride on various surfaces employed in drug manufacture is described.
      Cotton swabs, moistened with a methanol-water (1:1, v/v) mixture were used to
      remove any residues of drugs from glass, vinyl, and stainless steel surfaces, and
      gave recoveries of 85%, 78% and 90%, respectively. Residues were determined by
      high-performance liquid chromatography on a C18 column at 25 degrees C with
      methanol-ammonium acetate (40:60 v/v) pH 6.7 as the mobile phase and detection at
      320 nm. The method was validated over a concentration range of 20-10 000 ng/ml
      and had a detection limit of 2 ng/ml.

PMID- 11459316
TI  - Liquid chromatography of polyglycerol fatty esters and fatty ethers on porous
      graphitic carbon and octadecyl silica by using evaporative light scattering
      detection and mass spectrometry.
AB  - A liquid chromatographic method has been developed for the analysis of
      polyglycerol fatty esters and fatty ethers which are non-ionic surfactants. Two
      methods were compared using either octadecyl silica or porous graphitic carbon.
      The octadecyl silica system with a hydroorganic mobile phase enables to compare
      the hydrophobic behavior of the compounds. The porous graphitic carbon enables
      the separation of the diastereoisomers. Detection of these non-UV-absorbing
      compounds was achieved by evaporative light scattering detection. Identification
      of isomers was performed by mass spectrometry.

PMID- 11459317
TI  - Defensin antimicrobial peptides in the oral cavity.

PMID- 11459318
TI  - Influence of aging on candidal growth and adhesion regulatory agents in saliva.
AB  - Although oral candidiasis is frequently seen in the elderly, the factors
      determining candidal growth have insufficiently been explored. Hence, we examined
      the influence of aging on candidal adhesion and growth-inhibitory agents in
      saliva in 45 healthy volunteers and 60 patients with oral candidiasis. Both non
      stimulated and stimulated salivary flow rates (SFRs) in the healthy controls
      decreased with aging. A gradual decrease of SFRs with aging was also observed in
      the patients, and the SFR levels were markedly lower than those in the controls.
      Although the salivary glucose levels were almost constant in all age groups,
      secretory immunoglobulin A and lactoferrin levels in saliva were significantly
      decreased statistically with age, and a marginal age-associated decrease in
      transferrin levels was also observed. In addition, the generation of superoxide
      from neutrophils in saliva and their Candida killing activity decreased with age,
      and these phenomena were more apparent in the patients. Furthermore, a larger
      number of Candida adhered to oral keratinocytes obtained from the elderly healthy
      controls than to those obtained from young controls. Correspondingly,
      keratinocytes from the aged controls showed more concanavalin-A binding sites
      than those from the young controls. However, oral Candida did not increase with
      increasing age in the controls, although an age-associated increase of oral
      Candida was observed in the patients. Taken together, these results indicate that
      the decreases of SFRs and salivary anti-candidal factors, suppression of salivary
      neutrophil function and the increase of candidal adhesion sites on keratinocytes
      predispose elderly individuals to oral candidiasis.

PMID- 11459319
TI  - Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated
      on single and sequential visits from a HIV-infected southern Chinese cohort.
AB  - The increased frequency and severity of candidal infections in human
      immunodeficiency virus (HIV)-infected individuals has prompted the wide use of
      antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in
      the emergence of drug-resistant strains of Candida albicans. To study this
      phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida
      from the oral cavities of 16 HIV-infected patients on single and subsequent
      sequential visits over a period of 12 months. Ten of the 16 patients had sporadic
      episodes of oropharyngeal candidiasis (Group A), while the remainder were
      asymptomatic with respect to this condition (Group B). Oral rinses were collected
      and immediately processed in the laboratory for the isolation of C. albicans in a
      standard manner. A total of 433 C. albicans isolates were tested for their
      susceptibility to amphotericin B, ketoconazole and fluconazole by an agar
      diffusion method using the commercially available E-test. All tested isolates
      demonstrated variable susceptibility to amphotericin B, ketoconazole and
      fluconazole. The minimum inhibitory concentration (MIC) of the isolates for
      amphotericin B, ketoconazole and fluconazole ranged from <0.002-1.5 microg/ml,
      <0.002-4.0 microg/ml and <0.016-32 microg/ml, respectively. Sequential isolates
      of a few patients demonstrated variable susceptibility to all the antifungals,
      and no discernible MIC pattern emerged either in group A or B over time.
      Interestingly, significant variation in antifungal susceptibility was also noted
      in isolates obtained from the same patient on a single visit. Sequential yeast
      isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC
      within and between visits for both amphotericin B and ketoconazole, while a lower
      percentage--44%(7/16)--exhibited this trait for fluconazole. Our study
      demonstrates the diversity in antifungal susceptibility in either commensal or
      "infective" oral strains of C. albicans in HIV disease, and shows the need for
      vigilance for the emergence of resistant strains, and for frequent antifungal
      susceptibility studies.

PMID- 11459320
TI  - Oral Candida in HIV-infected heterosexuals and intravenous drug users in
      Thailand.
AB  - The objectives of this study were to determine levels of oral yeasts in Thai
      people at different stages of HIV infection compared with HIV-negative controls,
      to identify factors associated with the levels of oral Candida, and to determine
      whether the levels of the organism can be used as a predictive clinical marker in
      HIV-infected individuals. One hundred and eighty HIV-infected heterosexual
      persons and intravenous drug users (IVDUs) were enrolled (152 men, 28 women).
      Eighty-three HIV-free subjects from the same population were included as controls
      (48 men, 35 women). Oral yeasts were isolated in 103 HIV-infected subjects
      (57.2%) and 36 HIV-negative controls (43.3%). The mean number of colony forming
      units (CFU) of oral Candida in the first group was 1.9x10(4) CFU/ml (range
      2.2x10(2)-4.0x10(6) CFU/ml), which was significantly different statistically when
      compared with 1.7x10(3) CFU/ml (range 4.0x10(2)-1.2x10(5) CFU/ml) in the control
      group (P=0.0000). The following factors are significantly associated
      statistically with the levels of oral Candida among the subjects (P<0.05): age,
      stage of HIV infection, total number of lymphocyte cell count, risk group,
      nutritional status, general health status, weight loss, type of oral lesions and
      number of oral lesions and number of sites affected. The study revealed that HIV
      serostatus, stage of HIV infection, and the occurrence of oral lesions among HIV
      infected subjects may be predicted by the levels of oral Candida (P<0.05). By
      using a cut-off point of 2.0x10(3) CFU/ml, the sensitivity and predicitve values
      of the level of oral Candida on the HIV serostatus was higher than that based on
      the culture positivity results alone, although the specificity was similar. These
      findings suggest that, in conjunction with some other clinical signs and
      laboratory findings, the levels of oral Candida may be used as a predictive
      marker of disease in HIV infection.

PMID- 11459321
TI  - High risk human papillomavirus in oral squamous carcinoma: evidence of risk
      factors in a Venezuelan rural population. Preliminary report.
AB  - In a search for the presence of human papillomavirus (HPV) and some etiologic
      cofactors in oral squamous cell carcinoma (OSCC), 50 women diagnosed as OSCC were
      analyzed by a multiplex polymerase chain reaction (PCR) assay specific for HPV
      types 6, 11, 16, and 18. This study revealed that 60% (30/50) of the OSCC
      patients were positive for HPV-DNA sequences. This group was analyzed according
      to smoking, alcohol consumption, number of pregnancies, poor oral health and low
      social economic status. The current results indicate an increased incidence of
      HPV malignant types in the oral cavity in women with OSCC. Also, they support a
      multifactorial model of oral cancer causation.

PMID- 11459322
TI  - Effects of 5-fluorouracil on mitogen-induced costimulatory capacity of accessory
      cells from rat oral mucosa and dental pulp.
AB  - The present study was designed to investigate the effect of the antimetabolite 5
      fluorouracil (5-FU) on the capacity of the oral epithelium and the dental pulp to
      induce a mitogen-driven T-cell proliferation. Inbred Lewis rats were given 6 i.v.
      injections of 5-FU (30 mg/kg or 50 mg/kg) over a period of 8 days. Suspensions of
      oral epithelial and dental pulpal cells were prepared. The costimulatory capacity
      of the accessory cells from treated animals was monitored by their ability to
      induce a mitogen (ConA)-mediated proliferation of T cells isolated from regional
      lymph nodes of untreated animals. Accessory epithelial cells from rats treated
      with the high dose of 5-FU, but not the low dose, induced a decreased T-cell
      proliferation compared to controls. Accessory pulpal cells from rats, treated
      with 30 mg/kg or 50 mg/kg of 5-FU, induced a lower T-cell proliferation. When MHC
      class II molecule depleted T-cell suspensions from lymph nodes of 5-FU-injected
      animals were incubated with ConA, a significant proliferative response was
      observed. This finding correlated with an increase of MHC class II molecule
      expressing cells detected after incubation, although no such cells were observed
      immediately following the initial purification step of T cells. This finding
      demonstrates that the accessory cells could partly restore their expression of
      MHC class II molecules during incubation. The results of the study suggest that
      the function of immunocompetent cells of the oral mucosa and dental pulp is
      influenced by treatment with 5-FU and that the function of accessory cells of the
      pulp is affected more than the function of accessory cells derived from the oral
      mucosa.

PMID- 11459323
TI  - Cystic and glial mixed hamartoma of the tongue.
AB  - Choristomas and mixed hamartomas of the oral cavity are uncommon lesions that
      show a variety of clinical presentations, histological appearances and growth
      patterns. We report a case of an unusual mixed hamartoma of the posterior tongue
      composed of dermoid cyst, sebaceous and glial elements. Magnetic resonance
      imaging indicated a predominantly cystic lesion limited to the pharyngeal and
      posterior part of the anterior tongue. A conservative approach was adopted and
      the lesion has shown minimal growth for 2 years following diagnosis.

PMID- 11459324
TI  - Childhood oral pemphigoid: a case report and review of the literature.
AB  - Oral pemphigoid, defined as cicatricial pemphigoid limited to the oral cavity, is
      a clinical subset of cicatricial pemphigoid. Like cicatricial pemphigoid, it
      occurs mostly in middle-aged women and it is uncommon in children under 20 years
      of age. There are 11 cases of childhood cicatricial pemphigoid published
      previously in the English language literature, and four of them are oral
      pemphigoid patients. We present a case of the youngest oral pemphigoid patient
      reported yet. Because of the rareness of cicatricial pemphigoid in children,
      delayed diagnosis and treatment have been shown in many cases reported earlier.
      Clinical awareness and early recognition are, therefore, emphasized.

PMID- 11459325
TI  - Urachal carcinoma with metastasis to the maxilla: the first reported case.
AB  - A case is reported for the first time of a urachal carcinoma with metastasis to
      the maxilla. The patient presented with a hard swelling along the left upper jaw
      in the region of 24-27. At the time of onset there were skin changes and signs of
      metastasis to the brain. The patient died 13 months after the onset of symptoms.

PMID- 11459326
TI  - Identification of a stop codon mutation in the CBFA1 runt domain from a patient
      with cleidocranial dysplasia and cleft lip.
AB  - We examined a patient with cleidocranial dysplasia (CCD) and cleft lip and found
      a new stop codon mutation in CBFA1. This mutation was a heterozygous C-to-T
      transition in exon 3 of CBFA1. This nucleotide change converts a CAA codon to a
      TAA (stop) codon at amino acid position Gln195 in the runt domain of CBFA1.

PMID- 11459327
TI  - Who is interested in the quality of everyday psychiatric care?
AB  - In the past 50 years the treatment possibilities have drastically improved, but
      the treatment results achieved under everyday care conditions mainly lag far
      behind those that could actually be achieved. This efficacy-effectiveness gap is
      at present the main obstacle to achieving optimal outcome in psychiatry. In this
      editorial, several causative factors for this gap are named and suggestions are
      made as to what should be done to fulfill the outcome that is achievable
      according to today's state of knowledge. Estimates indicate that at least a 25%
      improvement of important outcome indicators (e.g. yearly relapse rates) could be
      achieved.

PMID- 11459328
TI  - Quality management in psychiatry.
AB  - Over the past 50 years, treatment possibilities in psychiatry have drastically
      improved, but the results we actually achieve under everyday treatment conditions
      fall far short of what could be accomplished. Quality management represents a
      suitable method of reducing this gap. Although it has been successfully practiced
      in other medical disciplines for a long time, its implementation in psychiatry
      has previously been restricted to pilot projects. Quality management programs in
      psychiatry have been slow to be accepted because, up to now, only a few mental
      health professionals have received training in quality management techniques. In
      order to compensate for this information deficit and to familiarize psychiatrists
      and other mental health care workers with this increasingly important topic, we
      will provide in this paper a brief survey of the most important principles and
      techniques of quality management. This information should encourage psychiatrists
      to apply this new method to their own areas of responsibility. The results of one
      of our own studies on schizophrenic outpatients, which are presented at the end
      of the paper, are intended to show that the outcome can be improved and costs
      reduced by implementing quality management programs in psychiatry.

PMID- 11459329
TI  - PQM--Psychiatry Quality Measurement.
AB  - As a consequence of an increased awareness of quality management in psychiatry
      the Lundbeck Institute has developed a software program called Psychiatry Quality
      Measurement (PQM). This is an electronic documentation and quality measurement
      system with a large data-collecting function to record longitudinal data of the
      full psychiatric visit, covering all aspects of an evaluation and follow-up.
      Using the full ICD-10 and DSM-IV classifications, the system has been designed to
      assist with quality measurement in all psychiatric diagnoses. A full statistical
      package is included in the program to calculate outcomes of treatment (including
      relapse rates, improvements in psychopathology, severity and frequency of side
      effects, and costs of treatment) as tables and graphs ready for presentation in a
      Powerpoint format. The system is fully translatable and flexible for various
      implementation settings, including stand-alone PCs or hospital network systems,
      all ICD-10 or DSM-IV diagnoses, and the possibility of the use of over 20
      psychopathology and side-effect scales to measure the quality of care of all
      psychiatry patients.

PMID- 11459330
TI  - DIABCARE Quality Network in Europe--a model for quality management in chronic
      diseases.
AB  - The DIABCARE Q-Net project developed a complete and integrated information
      technology system to monitor diabetes care, according to the gold standards of
      the St Vincent Declaration Action Program. This is the first Telematic platform
      for standardized documentation on medical quality and evaluation across Europe,
      which will serve as a model for other chronic diseases. Quality development
      starts from the comparison of diabetes services, based on the key data on
      diabetes care in the basic information sheet. This is a 141 field form, which is
      to be completed once a year for each patient under the care of the diabetes team.
      The system performs an analysis of the local data and compares the data with peer
      teams by means of telecommunication of anonymous data. These data are collected
      regionally. At the next level these regional data are compared on a national
      basis across Europe using dedicated communication lines. National data can be
      compared transnationally by the use of the Internet and the DIABCARE benchmarking
      servers. These different lines are used according to the necessary security
      standards. Medical data are transferred via dedicated lines, aggregated data via
      the Internet. The architecture follows the open-platform concept in order to
      allow for heterogeneous technical environments. Already at the start of the
      project, the necessity for expanding the quality approach to telemedicine
      methodology was identified and included. For each level, specific programs are
      available to improve the performance of diabetes care delivery: DIABCARE data as
      client and DIABCARE server as regional and DIABCARE 'international server' as
      transnational server. Functioning pilots were established across all levels. The
      clients have been linked to the servers on a routine basis. According to the open
      architecture design, the various countries decided on different systems at the
      entry point: full system--Portugal; fax systems--Italy, Bavaria; implementation
      into doctor's office systems--Norway; paper forms and chip cards--France. This
      system can improve the local, regional and national diabetes care. Initiatives in
      several countries proved the feasibility of the system. The most extensive use,
      from Portugal, will be reported later in this paper. The exploitation of the
      DIABCARE Q-Net system will be performed with the DIABCARE International European
      Economic Interest Grouping as a co-ordinator and several commercial companies as
      contractors to market the products inside the system. The key project
      participants are: DIABCARE Office EURO, DIABCARE Portugal, DIABCARE France,
      DIABCARE Bavaria, DIABCARE UK, DIABCARE Netherlands, DIABCARE Norway, DIABCARE
      Italy, DIABCARE Sweden, DIABCARE Austria, DIABCARE Spain, GSF Research Centre for
      Health and Environment, FAST Research Institute for Applied Software Technology,
      Tromso University Hospital, Stavanger Technical College, Technical University of
      Ilmenau, World Health Organisation (WHO), Regional Office for Europe.

PMID- 11459331
TI  - Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): efficacy
      and tolerability results of an international naturalistic study.
AB  - The Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS)
      programme was an international series of naturalistic studies designed to
      evaluate drug use patterns and outcomes. RODOS consisted of retrospective chart
      reviews performed in patients who had been admitted to hospital and treated in 61
      centres in nine countries. The analysed population consisted of 1901 patients
      with diagnoses of schizophrenia or schizoaffective disorder. The mean (SD) daily
      doses of risperidone and olanzapine were 5.3 (2.6) mg/day and 14.5 (5.1) mg/day,
      respectively. Patients treated with risperidone stayed an average of 3.8 days
      less in hospital compared to those receiving olanzapine (time to discharge was
      43.6 days versus 47.4 days, respectively; P = 0.004). Risperidone was rated as
      effective in significantly more patients than olanzapine (84% versus 79%; P =
      0.01). The time to onset of efficacy was significantly shorter with risperidone
      than with olanzapine (P < 0.001). The numbers of adverse events in the two
      treatment groups were not significantly different (13% risperidone, 11%
      olanzapine; P = 0.1). Correcting for small but statistically significant baseline
      differences between the two treatment groups did not produce a substantive change
      in the magnitude or significance of any outcome parameter. In conclusion, the
      clinical outcomes reported by RODOS suggest that risperidone may be more
      effective as a first-line therapy drug for schizophrenia than olanzapine.

PMID- 11459332
TI  - Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): health
      economic results of an international naturalistic study.
AB  - We report the health economic data from the Risperidone Olanzapine Drug Outcomes
      studies in Schizophrenia (RODOS) programme. Details of the efficacy and
      tolerability data from RODOS are available in a companion paper. The population
      analysed during RODOS consisted of 1901 patients with diagnoses of schizophrenia
      or schizoaffective disorder. The mean +/- SD daily dose of olanzapine treatment
      was 14.5 +/- 5.1 mg compared to 5.3 +/- 2.6 mg for risperidone. Use of
      concomitant neuroleptics (risperidone, 65%; olanzapine, 62%; P = 0.2) and other
      concomitant drugs (risperidone, 76%; olanzapine, 73%; P = 0.2) was similar in
      both groups. The mean +/- SD total costs of all inpatient drugs was significantly
      (P < 0.001) higher for olanzapine (US$ 297.5 +/- 305.1) than risperidone
      (US$159.9 +/- 183.3). Although this difference in the average total costs in part
      reflects the longer treatment duration for olanzapine compared to risperidone (34
      days versus 31 days), the cost difference remained when looking at costs on a
      daily basis. The mean +/- SD daily cost of all inpatient drugs was also
      significantly (P < 0.001) higher for olanzapine (US$7.7 +/- 4.0) than for
      risperidone (US$ 4.6 +/- 2.9). These findings were very consistent across all
      nine countries. The results from RODOS suggest that treatment costs are
      significantly higher with olanzapine than with risperidone without any clinical
      benefit to offset this.

PMID- 11459333
TI  - Olanzapine in the treatment of post-traumatic stress disorder: a pilot study.
AB  - Because the atypical antipsychotic olanzapine may be efficacious in treating post
      traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind,
      placebo-controlled evaluation in which 15 patients were randomized 2:1 to either
      olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a
      maximum of 20 mg/day. Eleven patients completed the study. Patients in both
      groups showed improvement in PTSD symptoms, but no between-group differences in
      treatment response were observed and a high placebo response rate was found. Both
      treatments were tolerated well, although the olanzapine treatment group had more
      weight gain. Olanzapine fared no better than placebo in this preliminary study in
      the treatment of PTSD. The lack of difference between olanzapine and placebo may
      in part be due to olanzapine's not being effective in PTSD or, alternatively, a
      small sample size, a high placebo response in certain forms of PTSD and the
      chronicity of PTSD symptoms in some patients.

PMID- 11459334
TI  - A model for handling missing items on two depression rating scales.
AB  - A problem in clinical trials for antidepressants is that patient rating scales
      are not always completed properly. If one or more items are missing, a patient
      evaluation may be prevented from contributing towards an efficacy analysis. This
      can be very wasteful, particularly if data are missing at a baseline evaluation.
      In this study, we present a novel approach to estimating missing item scores on
      both the Montgomery-Asberg Depression Rating Scale and the Beck Depression
      Inventory. Our approach works on the assumption that patient response is non
      uniform across items. By capturing the average between-item variation, we have
      developed a set of weights for each scale which can be used to predict missing
      item scores with high levels of accuracy. These weights were tested on several
      sets of patient data when one item was missing. The proposed weights are stable
      and will be of practical use to researchers in the field of Major Depression.

PMID- 11459335
TI  - Citalopram in refractory obsessive-compulsive disorder: an open study.
AB  - This study aimed to evaluate the effect of citalopram in patients with refractory
      obsessive-compulsive disorder (OCD) which had not responded to previous
      antiobsessional treatments. Eighteen patients were selected for this study: they
      had been suffering from OCD, according to DSM-IV criteria, for at least 2 years
      and had various comorbid disorders. All had been treated with serotonin reuptake
      inhibitors at adequate dosages for at least 6 months, but had failed to respond.
      Consequently, they were shifted to citalopram, titrated up to the dose of 40 mg,
      within 2 weeks. After 4 months of this regimen, 14 out of the total of 18
      patients had shown a reduction in OC symptoms, as assessed by the decrease in the
      Yale-Brown Obsessive Compulsive Scale total score; no relevant side-effects were
      reported, except for a mild nausea in four patients within the first few days of
      treatment, which quickly disappeared. The use of citalopram would appear to be an
      useful strategy in refractory OCD cases.

PMID- 11459336
TI  - Fluoxetine treatment in patients with recurrent brief depression.
AB  - Recurrent brief depression (RBD) fulfills DSM-IV criteria for major depression
      except duration. Depressive episodes last at least 2 days but less than 2 weeks
      occurring at least once a month for 12 consecutive months without association to
      the menstrual cycle. RBD has a high prevalence in the general population
      (approximately 10%). At present, there are few double-blind controlled studies
      indicating that selective serotonine reuptake inhibitors (SSRIs) might not be
      effective in treatment of RBD. However, most of those studies include patients
      with a history of frequent suicide attempts and depressive episodes lasting
      shorter 2 weeks. It has previously been shown that fluoxetine was effective in
      patients with RBD in an open-label study. The objective of our study was to
      reinvestigate these contradictory results concerning the effectiveness of
      fluoxetine in patients with RBD. Seventeen patients with RBD according to DSM-IV
      and ICD-10 diagnostic criteria, who had no history of major depression were
      treated with a dosage of 20-40 mg fluoxetine daily. Patients had to keep a diary
      in order to document psychopathological symptoms according to DSM-IV. We also
      used the 21-item Hamilton Depression Rating Scale (HAM-D), the Beck Depression
      Inventory (BDI) and the Clinical Global Impressions (CGI). Duration of the study
      was 8 weeks. The diaries of nine patients were observed for a clinical
      observation period of 20 weeks after the end of the study with continued
      fluoxetine treatment. Two patients who initially fulfilled diagnostic criteria
      for RBD suffered from depressive episodes that lasted longer than 2 weeks.
      Therefore, their data had to be excluded from primary analysis. In the remaining
      15 patients, we showed statistically significant improvement of depressive
      episodes measured by patient's diary, HIAM-D, BDI and CGI that persisted over the
      clinical observation period. Frequency of depressive episodes showed a
      significant decrease during fluoxetine treatment. Duration and severity of the
      single depressive episodes also decreased but did not reach statistical
      significance. In accordance with previous studies, fluoxetine could be a
      treatment option for patients with RBD. Treatment of RBD with SSRIs has been
      discussed controversially in the literature. Our study shows the effectiveness of
      fluoxetine in this depressive disorder. To confirm these preliminary results, a
      double-blind controlled study is necessary.

PMID- 11459337
TI  - Psychotropic drug use in Italy, 1984-99: the impact of a change in reimbursement
      status.
AB  - After years of corruption surrounding drug reimbursement, in 1994, a change in
      drug reimbursement status was implemented in Italy according to cost
      effectiveness criteria. The aim of this study was to assess the impact of these
      changes on the use of psychotropic drugs. National trends in antipsychotic,
      antidepressant and benzodiazepine prescriptions were analysed from 1984 to 1999.
      During the study period, prescriptions of antipsychotic drugs were stable from
      1984 to 1994 but, in the subsequent 5 years, increased by 54%. Although the use
      of atypical compounds in 1999 accounted for only 6% of total antipsychotics sold,
      the cost of these new drugs accounted for almost one-half the total antipsychotic
      expenditure. The use of benzodiazepines increased by 53%. In 1999, the
      psychotropic drugs lorazepam and alprazolam were the most sold by value. From
      1984 to 1999, the total antidepressants sold increased by 55%. Although the use
      of selective serotonin reuptake inhibitors and newer antidepressants in 1999
      accounted for less than 50% of total antidepressants sold, the cost of these
      drugs accounted for 65% of total antidepressant expenditure. This analysis
      highlights specific areas of concern which should become the object of public
      health programs.

PMID- 11459338
TI  - Allopurinol augmentation for poorly responsive schizophrenia.
AB  - Adenosine has been proposed to contribute to the pathophysiology of schizoprenia
      and as a target for therapeutic intervention. In the lack of direct adenosine
      agonists, allopurinol may indirectly elevate adenosine levels by inhibiting
      degradation of purines. We report two cases of poorly responsive schizophrenic
      patients who improved considerably with add-on allopurinol 300 mg/day. Their
      clear clinical improvement warrant further investigation of allopurinol, as well
      as other purinergic strategies, for the treatment of schizophrenia.

PMID- 11459339
TI  - Fenestral pore size in the internal elastic lamina affects transmural flow
      distribution in the artery wall.
AB  - Interstitial flow through the subendothelial intima and media of an artery wall
      was simulated numerically to investigate the water flow distribution through
      fenestral pores which affects the wall shear stress on smooth muscle cells right
      beneath the internal elastic lamina (IEL). A two-dimensional analysis using the
      Brinkman model of porous media flow was performed. It was observed that the
      hydraulic permeability of the intimal layer should be much greater than that of
      the media in order to predict a reasonable magnitude for the pressure drop across
      the subendothelial intima and IEL (about 23 mostly at a 70 mm Hg luminal
      pressure). When Ki was set equal to the value in the media, this pressure drop
      was unrealistically high. Furthermore, the higher value of Ki produced a nearly
      uniform distribution of water flow through a simple array of fenestral pores all
      having the same diameters (1.2 microm), whereas when Ki was set at the value in
      the media, the flow distribution through fenestral pores was highly nonuniform
      and nonphysiologic. A deformable intima model predicted a nonuniform flow
      distribution at high pressure (180 mm Hg). Damage to the IEL was simulated by
      introducing a large fenestral pore (up to 17.8 microm) into the array. A dramatic
      increase in flow through the large pore was observed implying an altered fluid
      mechanical environment on the smooth muscle cells near the large pore which has
      implications for intimal hyperplasia and atherosclerosis. The model also
      predicted that the fluid shear stress on the bottom surface of an endothelial
      cell is on the order of 10 dyne/cm2, a level which can affect cell function.

PMID- 11459340
TI  - Contractile responses in arteries subjected to hypertensive pressure in seven-day
      organ culture.
AB  - Early stage changes in hypertensive arteries have a significant effect on the
      long-term adaptation of the arteries. Compared to the long-term adaptation,
      little is known about the early dimensional and functional changes in
      hypertensive arteries in the first few days of hypertension. To study the early
      stage changes in hypertensive arteries, porcine common carotid arteries were
      cultured for seven days in a simplified ex vivo artery organ culture system with
      pulsatile flow under hypertensive (200+/-30 mm Hg) or normotensive (100+/-20 mm
      Hg) pressure conditions while maintaining a physiological mean wall shear stress
      of 15 dyn/cm2. Vessel viability was demonstrated by contractile diameter
      responses to norepinephrine (NE), carbachol (CCh), and sodium nitroprusside (SNP)
      as well as staining for mitochondrial activity and cell apoptosis/necrosis. The
      results show that arteries demonstrated strong contractile responses to NE, CCh,
      and SNP, basal tone, and viable mitochondria in the organ culture system for
      seven days. Hypertensive arteries demonstrated a stronger contractile response
      than normotensive arteries (p<0.05). Diameter enlargement was observed in
      hypertensive arteries as compared to arteries cultured under normotensive
      conditions. In conclusion, the pulsatile culture system can maintain arteries
      viable with active vasomotion tone for up to seven days. Hypertensive pressure
      causes arterial adaptation by significantly increasing arterial diameter and
      contractile response within the first seven days.

PMID- 11459341
TI  - Chondrocyte differentiation is modulated by frequency and duration of cyclic
      compressive loading.
AB  - As part of a program of research aimed at determining the role of mechanical
      forces in connective tissue differentiation, we have developed a model for
      investigating the effects of dynamic compressive loading on chondrocyte
      differentiation in vitro. In the current study, we examined the influence of
      cyclic compressive loading of chick limb bud mesenchymal cells to a constant peak
      stress of 9.25 kPa during each of the first 3 days in culture. Cells embedded in
      agarose gel were subjected to uniaxial, cyclic compression at 0.03, 0.15, or 0.33
      Hz for 2 h. In addition, load durations of 12, 54, or 120 min were evaluated
      while holding frequency constant at 0.33 Hz. For a 2 h duration, there was no
      response to loading at 0.03 Hz. A significant increase in chondrocyte
      differentiation was associated with loading at 0.15 Hz, and an even greater
      increase with loading at 0.33 Hz. Holding frequency constant at 0.33 Hz, a
      loading duration of 12 min elicited no response, whereas chondrocyte
      differentiation was enhanced by loading for either 54 or 120 min. Although not
      statistically significant from the 120 min response, average cartilage nodule
      density and glycosaminoglycan synthesis rate were highest in the 54 min duration
      group. This result suggests that cells may be sensitive to the level of
      cumulative (nonrecoverable) compressive strain, as well as to the dynamic strain
      history.

PMID- 11459342
TI  - Classification of endocardial electrograms using adapted wavelet packets and
      neural networks.
AB  - The discrimination of ventricular tachycardias with 1:1 retrograde conduction
      from sinus tachycardia still remains a challenge for rate based algorithms
      commonly used in dual-chamber implantable cardioverter defibrillators. Morphology
      based analysis techniques for a classification of antegrade and retrograde atrial
      activation patterns can be used to cope with this problem. Here time-domain
      template matching techniques are known approaches. However, a time-domain
      representation of endocardial electrograms is not optimal for classification
      tasks as the dimensionality of the underlying signal space is high and features
      being irrelevant for a signal characterization are involved in the analysis.
      Therefore, the aim of this study is to develop an enhanced morphological analysis
      tool for a classification of antegrade and retrograde atrial activation by using
      a transform domain representation of endocardial electrograms. For this, we
      applied an adapted wavelet-packet decomposition to extract discriminating
      features in endocardial electrograms representing antegrade and retrograde
      activation patterns. Further, a feed-forward neural network was utilized to
      produce a classification based on the extracted information. In using our hybrid
      method, no false classification of the physiological and pathological cardiac
      state was made. It is concluded that the proposed classification scheme
      represents a highly efficient approach for a classification of antegrade and
      retrograde atrial activation.

PMID- 11459343
TI  - Global comparisons between contact and noncontact mapping techniques in the right
      atrium: role of cavitary probe size.
AB  - In the right atrium (RA) we globally investigated: (1) the properties of
      noncontact electrograms measured by multielectrode cavitary probes, (2) the
      features of endocardial electrograms computed from the noncontact probe
      electrograms, and (3) the impact of the probe size on both the noncontact and the
      computed electrograms. We deployed a custom catheter in the dog RA, which
      consisted of a cylindrical probe with 64 electrodes on its surface, for measuring
      noncontact cavitary electrograms, and a concentric endocardial basket carrying an
      additional array of 64 electrodes, for measuring contact endocardial electrograms
      (the "gold standard"). Both a 5-mm- and a 10-mm-diam probe (P5 and P10,
      respectively) were sequentially tested in the same RA of one dog. Unipolar
      electrograms from both the probe and the basket were simultaneously acquired
      during normal as well as during paced rhythms (n > or =24 protocols per probe).
      Boundary element method and numeric regularization were applied to compute
      endocardial electrograms at the basket electrode locations. We found that
      noncontact electrograms were attenuated and smoothed, and this effect was
      exaggerated with the small probe. Computed endocardial electrograms more
      accurately reconstructed important amplitude distribution and morphological
      features; peak-to-peak amplitude error, 35% for P5 and 34% for P10. Activation
      and spatial errors of computed endocardial electrograms were 8.8+/-6.8 ms and
      5.1+/-6.1 mm for P5, respectively, and 6.0+/-5.5 ms and 3.2+/-4.4 mm for P10,
      respectively. In conclusion, global RA activation may be delineated directly from
      noncontact cavitary electrograms alone, but may be affected by volume
      attenuation, smoothing, and probe size. Accurate endocardial electrograms,
      however, can be successfully computed from noncontact electrograms acquired with
      small probes and be used to reconstruct both electrogram amplitude and detailed
      morphology.

PMID- 11459344
TI  - Magnetocardiographic and electrocardiographic exercise mapping in healthy
      subjects.
AB  - In 12-lead electrocardiography (ECG), detection of myocardial ischemia is based
      on ST-segment changes in exercise testing. Magnetocardiography (MCG) is a
      complementary method to the ECG for a noninvasive study of the electric activity
      of the heart. In the MCG, ST-segment changes due to stress have also been found
      in healthy subjects. To further study the normal response to exercise, we
      performed MCG mappings in 12 healthy volunteers during supine bicycle ergometry.
      We also recorded body surface potential mapping (BSPM) with 123 channels using
      the same protocol. In this paper we compare, for the first time, multichannel MCG
      recorded in bicycle exercise testing with BSPM over the whole thorax in middle
      aged healthy subjects. We quantified changes induced by the exercise in the MCG
      and BSPM with parameters based on signal amplitude, and correlation between
      signal distributions at rest and after exercise. At the ST-segment and T-wave
      apex, the exercise induced a magnetic field component outward the precordium and
      the minimum value of the MCG signal over the mapped area was found to be
      amplified. The response to exercise was smaller in the BSPM than in the MCG. A
      negative component in the MCG signal at the repolarization period of the cardiac
      cycle should be considered as a normal response to exercise. Therefore, maximum
      ST-segment depression over the mapped area in the MCG may not be an eligible
      parameter when evaluating the presence of ischemia.

PMID- 11459345
TI  - Use of a genetic algorithm for the analysis of eye movements from the linear
      vestibulo-ocular reflex.
AB  - It is common in vestibular and oculomotor testing to use a single-frequency
      (sine) or combination of frequencies [sum-of-sines (SOS)] stimulus for head or
      target motion. The resulting eye movements typically contain a smooth tracking
      component, which follows the stimulus, in which are interspersed rapid eye
      movements (saccades or fast phases). The parameters of the smooth tracking--the
      amplitude and phase of each component frequency--are of interest; many methods
      have been devised that attempt to identify and remove the fast eye movements from
      the smooth. We describe a new approach to this problem, tailored to both single
      frequency and sum-of-sines stimulation of the human linear vestibulo-ocular
      reflex. An approximate derivative is used to identify fast movements, which are
      then omitted from further analysis. The remaining points form a series of smooth
      tracking segments. A genetic algorithm is used to fit these segments together to
      form a smooth (but disconnected) wave form, by iteratively removing biases due to
      the missing fast phases. A genetic algorithm is an iterative optimization
      procedure; it provides a basis for extending this approach to more complex
      stimulus-response situations. In the SOS case, the genetic algorithm estimates
      the amplitude and phase values of the component frequencies as well as removing
      biases.

PMID- 11459346
TI  - Ligand coated nanosphere adhesion to E- and P-selectin under static and flow
      conditions.
AB  - The heterogeneous distribution of endothelial cell adhesion molecules (ECAMs) on
      the lumenal surface of vascular endothelium provides an opportunity to deliver
      drugs to select tissues. The targeting could be achieved by using carriers whose
      outer surface has a ligand for a selectively expressed ECAM. The carriers would
      interact with the endothelium in a fluid dynamic environment and in many of these
      schemes nanoparticles would be used. It is unclear what role various parameters
      (e.g., ligand-ECAM chemistry, fluid shear) will have on the adhesion of the
      nanoparticles to the endothelium. To facilitate studies in this area, we have
      developed a prototypical in vitro model that allows investigation of nanoparticle
      adhesion. We coated polystyrene nanospheres with a humanized mAb (HuEP5C7.g2)
      that recognizes the ECAMs E- and P-selectin. Adhesion assays revealed that
      HuEP5C7.g2 nanospheres exhibit augmented, specific adhesion to selectin
      presenting cellular monolayers and that the adhesion can be affected by the fluid
      shear. These results; (i) strongly suggest that HuEP5C7.g2 could be used to
      target nanoparticles to selectin presenting endothelium; (ii) demonstrate that
      fluid shear can affect nanoparticle adhesion; and (iii) define a system which can
      be used to study the effects of various system parameters on nanoparticle
      adhesion.

PMID- 11459347
TI  - Towards understanding life itself.

PMID- 11459348
TI  - Robert Rosen (1934-1998): a snapshot of biology's Newton.

PMID- 11459349
TI  - Which craft is best in bioinformatics?
AB  - 'Silicon-based' biology has gathered momentum as the world-wide sequencing
      projects have made possible the investigation and comparative analysis of
      complete genomes. Central to the quest to elucidate and characterise the genes
      and gene products encoded within genomes are pivotal concepts concerning the
      processes of evolution, the mechanisms of protein folding, and, crucially, the
      manifestation of protein function. Our use of computers to model such concepts is
      limited by, and must be placed in the context of, the current limits of our
      understanding of these biological processes. It is important to recognise that we
      do not have a common understanding of what constitutes a gene; we cannot
      invariably say that a particular sequence or fold has arisen via divergence or
      convergence; we do not fully understand the rules of protein folding, so we
      cannot predict protein structure; and we cannot invariably diagnose protein
      function, given knowledge only of its sequence or structure in isolation.
      Accepting what we cannot do with computers plays an essential role in forming an
      appreciation of what we can do. Without this understanding, it is easy to be
      misled, as spurious arguments are often used to promote over-enthusiastic notions
      of what particular programs can achieve. There are valuable lessons to be learned
      here from the field of artificial intelligence, principal among which is the
      realisation that capturing and representing complex knowledge is time consuming,
      expensive and hard. If bioinformatics is to tackle biological complexity
      meaningfully, the road ahead must therefore be paved with caution, rigour and
      pragmatism.

PMID- 11459350
TI  - The emergence of complexity: science coming of age or science growing old?
AB  - The emergence of a new field of science called complexity theory has made an
      impact on the community of scientists as well as the general public. This brief
      tutorial takes a very special view of this. The thesis is that complexity science
      has grown out of a general lack of satisfaction with traditional scientific
      practices and their failure to find a way of capturing anything but a shadow of
      complex reality. In spite of the many impressive advances from science and
      technology, it is clear that the picture delivered of the world is that of a
      surrogate world populated by machines and mechanisms. The nature of the real
      world demands more than traditional science can deliver. Yet traditional science
      has constraints and bounds on its universe of discourse. Complexity science, as
      presented here, demands that the barriers and constraints be removed in order to
      gain a more complete view of nature. This tutorial presents a summary of what is
      entailed by this new methodology.

PMID- 11459351
TI  - Non-equilibrium proteins.
AB  - There exist no methodical studies concerning non-equilibrium systems in cellular
      biology. This paper is an attempt to partially fill this shortcoming. We have
      undertaken an extensive data-mining operation in the existing scientific
      literature to find scattered information about non-equilibrium subcellular
      systems, in particular concerning fast proteins, i.e. those with short turnover
      half-time. We have advanced the hypothesis that functionality in fast proteins
      emerges as a consequence of their intrinsic physical instability that arises due
      to conformational strains resulting from co-translational folding (the
      interdependence between chain elongation and chain folding during biosynthesis on
      ribosomes). Such intrinsic physical instability, a kind of conformon (Klonowski
      Klonowska conformon, according to Ji, (Molecular Theories of Cell Life and Death,
      Rutgers University Press, New Brunswick, 1991)) is probably the most important
      feature determining functionality and timing in these proteins. If our hypothesis
      is true, the turnover half-time of fast proteins should be positively correlated
      with their molecular weight, and some experimental results (Ames et al., J.
      Neurochem. 35 (1980) 131) indeed demonstrated such a correlation. Once the native
      structure (and function) of a fast protein macromolecule is lost, it may not be
      recovered--denaturation of such proteins will always be irreversible; therefore,
      we searched for information on irreversible denaturation. Only simulation and
      modeling of protein co-translational folding may answer the questions concerning
      fast proteins (Ruggiero and Sacile, Med. Biol. Eng. Comp. 37 (Suppl. 1) (1999)
      363). Non-equilibrium structures may also be built up of protein subunits, even
      if each one taken by itself is in thermodynamic equilibrium (oligomeric proteins;
      sub-cellular sol-gel dissipative network structures).

PMID- 11459352
TI  - Network thermodynamics and complexity: a transition to relational systems theory.
AB  - Most systems of interest in today's world are highly structured and highly
      interactive. They cannot be reduced to simple components without losing a great
      deal of their system identity. Network thermodynamics is a marriage of classical
      and non-equilibrium thermodynamics along with network theory and kinetics to
      provide a practical framework for handling these systems. The ultimate result of
      any network thermodynamic model is still a set of state vector equations. But
      these equations are built in a new informative way so that information about the
      organization of the system is identifiable in the structure of the equations. The
      domain of network thermodynamics is all of physical systems theory. By using the
      powerful circuit simulator, the Simulation Program with Integrated Circuit
      Emphasis (SPICE), as a general systems simulator, any highly non-linear stiff
      system can be simulated. Furthermore, the theoretical findings of network
      thermodynamics are important new contributions. The contribution of a metric
      structure to thermodynamics compliments and goes beyond other recent work in this
      area. The application of topological reasoning through Tellegen's theorem shows
      that a mathematical structure exists into which all physical systems can be
      represented canonically. The old results in non-equilibrium thermodynamics due to
      Onsager can be reinterpreted and extended using these new, more holistic concepts
      about systems. Some examples are given. These are but a few of the many
      applications of network thermodynamics that have been proven to extend our
      capacity for handling the highly interactive, non-linear systems that populate
      both biology and chemistry. The presentation is carried out in the context of the
      recent growth of the field of complexity science. In particular, the context used
      for this discussion derives from the work of the mathematical biologist, Robert
      Rosen.

PMID- 11459353
TI  - Information theory in ecology.
AB  - The application of information theory (IT) to ecology has occurred along two
      separate lines: (1) it has been used to quantify the distribution of stocks and
      numbers of organisms; and (2) it has been employed to quantify the pattern of
      interactions of trophic processes. By and large, the first endeavor has resulted
      in relatively few insights into ecosystem dynamics and has generated much
      ambiguity and disappointment, so that most ecologists remain highly skeptical
      about the advisability of applying IT to ecology. By contrast, the second, and
      less well-known application has shed light on the possibility that ecosystem
      behavior is the most palpable example of a purely natural 'infodynamics' that
      transcends classical dynamics, but remains well within the realm of quantitative
      description.

PMID- 11459354
TI  - Sequence alignment: an approximation law for the Z-value with applications to
      databank scanning.
AB  - The Z-value is an attempt to estimate the statistical significance of a Smith and
      Waterman dynamic programming alignment score (H-score) through the use of a Monte
      Carlo procedure. In this paper, we give an approximation for the Z-value law
      deduced from the Poisson clumping heuristic developed by Waterman and Vingron
      (Stat. Sci. 9 (1994) 367) in the case of independent and identically distributed
      sequences comparison. As for non-gapped alignment scores, our approximation is of
      Gumbel type but with parameters that are sequence independent. This result makes
      clear the related experimental results mentioned by Comet et al. (Comput. Chem.
      23 (1999) 317). Using 'quasi-real' sequences (i.e. randomly shuffled sequences of
      the same length and amino acid composition as the real ones) we investigate the
      relevance of our approximation result. Since the Monte-Carlo approach we use
      generates a bias for the Gumbel decay parameter estimation, a correction
      procedure is proposed. Applications to real sequences are considered and we show
      how our results can be used to detect the potential biological relationships
      between real sequences.

PMID- 11459355
TI  - Amino acid residue environments and predictions of residue type.
AB  - The determination of a protein's structure from the knowledge of its linear chain
      is one of the important problems that remains as a bottleneck in interpreting the
      rapidly increasing repository of genetic sequence data. One approach to this
      problem that has shown promise and given a measure of success is threading. In
      this approach contact energies between different amino acids are first determined
      by statistical methods applied to known structures. These contact energies are
      then applied to a sequence whose structure is to be determined by threading it
      through various known structures and determining the total threading energy for
      each candidate structure. That structure that yields the lowest total energy is
      then considered the leading candidate among all the structures tested. Additional
      information is often needed in order to support the results of threading studies,
      as it is well known in the field that the contact potentials used are not
      sufficiently sensitive to allow definitive conclusions. Here, we investigate the
      hypothesis that the environment of an amino acid residue realized as all those
      residues not local to it on the chain but sufficiently close spatially can supply
      information predictive of the type of that residue that is not adequately
      reflected in the individual contact energies. We present evidence that confirms
      this hypothesis and suggests a high order cooperativity between the residues that
      surround a given residue and how they interact with it. We suggest a possible
      application to threading.

PMID- 11459356
TI  - Factors associated with HIV-infected women's use or intention to use AZT during
      pregnancy.
AB  - Despite the effectiveness of the antiviral drug AZT (zidovudine) in reducing
      perinatal transmission, many HIV-infected women continue to have reservations
      about taking the medication during pregnancy. To examine the factors influencing
      HIV-infected women's willingness to take AZT during pregnancy, focused interviews
      were conducted with 51 HIV-infected women of reproductive age living in New York
      City. Nearly all the women held reservations about taking it during pregnancy.
      Barriers to their use of AZT during pregnancy included (a) fear of toxic effects
      on baby, (b) fear of toxic effects for themselves, (c) fear of drug resistance,
      (d) belief that AZT is unnecessary among "healthy" women, and (e) previous birth
      to a healthy baby without using AZT. However, several factors also positively
      increased women's willingness to take AZT during pregnancy: (a) belief that they
      owe it to the baby to take AZT, (b) positive relationships with their physician,
      (c) peers or friends have taken AZT during pregnancy, and (d) previous experience
      taking AZT during pregnancy. These findings suggest significant areas for
      intervention to increase the use of AZT during pregnancy, thereby reducing
      perinatal transmission.

PMID- 11459357
TI  - How injection drug users coped with testing HIV-seropositive: implications for
      subsequent health-related behaviors.
AB  - At entry into methadone maintenance treatment, 94 HIV-positive injection drug
      users (IDUs) completed the Coping Reponses Inventory, which asked them to
      "describe your feelings and experiences when you first learned you were HIV
      positive." Controlling for time since HIV testing, a reliance on avoidance coping
      following HIV testing was correlated with high levels of recent HIV risk behavior
      and poor health at entry into the study. The use of any coping strategy,
      particularly approach strategies, was related to medication adherence.
      Hierarchical regression analysis showed that avoidance coping accounted for a
      significant proportion of the variance in recent HIV risk behavior over and above
      that accounted for by the other variables. Other independent predictors of
      continued risk behavior were poor health, lack of social support, and low levels
      of HIV/AIDS knowledge. The need for interventions to help injection drug users
      (IDUs) cope subsequent to testing HIV seropositive is discussed.

PMID- 11459358
TI  - Public reactions to people with HIV/AIDS in The Netherlands.
AB  - A national telephone survey was conducted to (a) assess present-day public
      reactions to people with HIV/AIDS in the Netherlands, (b) measure how knowledge
      about highly active antiretroviral therapy (HAART) is related to public reactions
      to people with HIV/AIDS, and (c) investigate determinants of willingness to have
      personal contact with people with HIV/AIDS. Dutch adults (N = 751) participated
      in a telephone interview conducted to measure cognitive, emotional, and
      behavioral reactions to people with HIV/AIDS. This study has shown that public
      reactions to people with HIV/AIDS seem to be moderately positive in the
      Netherlands. Knowledge about HAART is related to lower risk perceptions, a
      positive attitude toward homosexuals, less fear, and more willingness to have
      personal contact with people with HIV/AIDS. In particular, cognitive and
      emotional factors are meaningfully related to willingness to have personal
      contact with people with HIV/AIDS. Implications for Dutch AIDS educational
      campaigns aimed at stigma reduction are discussed.

PMID- 11459359
TI  - A street intercept survey to assess HIV-testing attitudes and behaviors.
AB  - Nationally, it has been estimated that 44% of adults in the United States have
      been tested for HIV, with substantial individual and community-level variations
      in HIV-testing attitudes and behaviors. HIV-testing behaviors and intentions and
      attitudes toward HIV testing, particularly toward home tests, were assessed among
      385 adults recruited in a street intercept survey from a gay-identified agency, a
      substance-abuse treatment program, and inner-city community venues (a shopping
      mall and community center). Across these Los Angeles sites, the proportion of
      persons reported being tested for HIV in their lifetime (77%) was higher than the
      national estimate. Gay-identified agency (88%) and substance-abuse treatment
      program participants (99%) were more likely to have been tested than were the
      community participants (67%). Participants from a gay-identified agency were more
      likely to have had an anonymous test (51%) than were those from a substance-abuse
      treatment program (25%) or community sites (24%). Attitudes toward HIV testing,
      including mail-in home-test kits and instant home tests, were very positive. Most
      participants were willing to pay about $20 for a home-test kit. Participants from
      the community sites (82%) and the substance-abuse treatment program participants
      (87%) endorsed notification of HIV status to health departments and sexual
      partners more than did participants from the gay identified agency (48%). The
      street intercept survey appears to be a quick and feasible method to assess HIV
      testing in urban areas.

PMID- 11459360
TI  - Women's HIV transmission risk perceptions and behaviors in the era of potent
      antiretroviral therapies.
AB  - The availability of potent antiretroviral medications has raised new concerns
      regarding continued HIV transmission risk behavior among seropositive persons.
      Relatively little is known about how women with HIV perceive secondary
      transmission risk in the context of HIV treatment advances. This study describes
      sexual risk perceptions and behaviors of 80 women enrolled in HIV outpatient care
      in 1999. Participants completed structured interviews assessing sexual risk
      perceptions, attitudes regarding severity of HIV disease, sources of HIV
      prevention information, and sexual practices during the previous 6 months.
      Medical histories including 6-month cumulative incidence of sexually transmitted
      diseases (STDs) were obtained from a clinic database. Thirty-five percent of the
      sample had engaged in unprotected intercourse or had been diagnosed with an STD
      in the past 6 months. Only 5% of women believed that medication-related
      reductions in viral load signify safer sex is unimportant, but 15% indicated they
      practice safer sex less often since the advent of new HIV treatments and 40%
      believed AIDS is now a less serious threat. These data suggest women's
      perceptions of diminished disease severity may be more influential than beliefs
      regarding diminished infectivity. Study results have implications for framing
      prevention messages for women and suggest that close integration of secondary
      prevention and clinical HIV services may be beneficial.

PMID- 11459361
TI  - Consistent condom use with different types of partners: evidence from two
      Nigerian surveys.
AB  - HIV prevalence in Nigeria is increasing rapidly. Increased condom use is the most
      viable solution to slow down or reverse this trend. This article uses data from
      two waves of a nation-wide survey, each with over 5,000 respondents, to examine
      factors that influence consistency of condom use with various types of partners.
      The results show that while the overall level of consistent condom use has
      remained low, reported consistent condom use with occasional partners and
      commercial sex workers exceeds 60%. There is also some evidence of an increasing
      trend in consistent condom use, even after controlling for differences in sample
      composition and other factors. The most important factors affecting consistency
      of condom use are awareness that condoms are effective at preventing HIV and that
      they are effective at preventing unwanted pregnancy, concern about unwanted
      pregnancy, and concern about HIV. Although concern about unwanted pregnancy has a
      strong effect on consistency of condom use with stable partners, concern about
      HIV infection has a strong effect on consistency of condom use with nonstable
      partners. The results suggest that HIV prevention programs need to do more than
      provide education about the modes of transmission and the ways to prevent
      infection. Improving the effectiveness of HIV prevention programs is likely to
      require focusing more explicitly on people's personal risk perception and condom
      efficacy. Focusing on these topics may further accelerate the observed positive
      trend in condom use.

PMID- 11459362
TI  - Developing standards in behavioral surveillance for HIV/STD prevention.
AB  - HIV/STD prevention programs are increasingly guided by behavioral rather than by
      disease indicators. Relevant HIV/STD-related behavioral information is currently
      available from a variety of surveys and surveillance systems at three levels:
      general population, infected populations, and high-risk populations. However, the
      utility of these systems for local program development is limited due to lack of
      standardization. In 1997 a Centers for Disease Control and Prevention working
      group was formed to develop a core set of items for HIV/STD behavioral
      surveillance for use across surveys. Core items were chosen on the basis of
      existing surveys and surveillance systems, relevant literature, testing in a
      cognitive laboratory, and field pilot-testing. A draft of the core set of sexual
      behavior questions is available on the web at http://www.cdc.gov/nchstp/od/core
      workgroup for review and feedback. Questions on drug use, including drug
      injection practices, as well as questions on HIV testing and sexually transmitted
      diseases are in preparation and will also be posted on the web site for review.

PMID- 11459363
TI  - Low impact of a community-wide HIV testing and counseling program on sexual
      behavior in rural Uganda.
AB  - Study results on the assessment of a community-wide HIV counseling and testing
      program are presented. The aim of this study was to elucidate whether HIV
      counseling and testing was effective in reducing high risk sexual behavior of a
      rural population in Uganda. From a total of 2,267 persons of Kigoyera Parish,
      western Uganda, who were HIV tested and counseled, 495 persons were selected and
      interviewed about their sexual behavior. Persons who were HIV tested showed no
      difference in sexual behavior compared to those who were not tested (condom use
      4.3% vs. 5.5%, mean number of sexual partner in the past three months 1.8 vs.
      2.0). The conclusion is that only knowing the HIV serostatus is not enough to
      reduce high risk behavior. The study results also showed that there is a demand
      for HIV counseling services without being HIV tested.

PMID- 11459364
TI  - Depressive symptoms among women receiving welfare.
AB  - Using data from an ongoing study of welfare recipients and their preschool-aged
      children, this study examined levels and correlates of self-reported depressive
      symptoms, and factors predicting transition off welfare assistance, among 173 low
      income, single, African American mothers. Forty percent reported symptom levels
      that are likely to indicate a diagnosis of clinical depression, and very few had
      received any mental health services. Mothers who had lived as children in
      households that received AFDC, who had received AFDC themselves for more than
      five years, who perceived less social support to be available to them, and who
      reported more life stressors, had significantly higher levels of depressive
      symptoms. Controlling for these factors associated with depression, women with
      higher symptom levels were slightly less likely to stop receiving AFDC tor some
      period of time over the two years of the study, but were no less likely to work
      or attend school. Implications of these findings for the development of programs
      and services for families on welfare are discussed.

PMID- 11459365
TI  - Impediments to employment under welfare reform: the importance of physical health
      and psychosocial characteristics.
AB  - The impact of Connecticut's welfare reform program (Jobs First), physical and
      mental health status, personal resources and household violence on employment was
      examined 18 months after women were randomized to either the welfare reform or
      the older AFDC program. Multivariate analyses showed that although the Jobs First
      program was statistically significantly associated with women having worked
      sometime since assignment to the welfare reform program, the Jobs First program
      was not associated with women currently working or having worked at some point
      but no longer working. Rather, women were more likely to be working at the 18
      month interview if they reported frequent help from their social networks (OR =
      1.52; p = .009), they had at least a high school degree (OR = 1.65; p =.002) and
      they were in good physical health (OR = 3.41; p = .009). Women who had worked
      sometime since random assignment but were no longer working at the 18 month
      interview reported few social contacts (OR = 1.33; p = .042), did not pay rent or
      own their own homes (OR = 6.94; p = .025), reported receiving AFDC for 2 years or
      more prior to randomization (OR = 1.83; p = .035) and reported high levels of
      household violence (OR = 1.52; p = .035). The need for attention to be focused on
      the importance of health problems, household violence and personal resources for
      the successful transitioning from public income support to employment is
      discussed.

PMID- 11459366
TI  - Associations between employment and financial and parental stress in low-income
      single black mothers.
AB  - Using a sample of 188 low-income single black mothers (93 employed and 95
      nonemployed), this study investigated financial strain, maternal depressive
      affect, and parenting stress among former welfare recipients who are now working,
      and current welfare recipients who are not employed. The findings suggested that
      being employed did not reduce financial strain, as the two groups reported
      similar levels of strain. However, regression analyses indicated that not being
      employed was associated with reporting higher levels of stress. Parenting stress
      was also associated with attaining less education, having boys, reporting more
      financial strain and depressive affect. Correlates of maternal depressive affect
      were mother's education and financial strain. Interaction effects were found for
      employment by financial strain, indicating that higher levels of depressive
      affect were related to more financial strain among nonemployed mothers. The
      findings suggest that although employment is associated with better mental health
      for poor mothers, entry into the workforce is associated with stronger links
      between financial strain, parenting stress and depressive affect for mothers
      leaving welfare.

PMID- 11459367
TI  - Future employment among homeless single mothers: the effects of full-time work
      experience and depressive symptomatology.
AB  - This study examines the relationship between work and depressive symptomatology
      for extremely destitute single mothers-mothers who have experienced an episode of
      homelessness. Using longitudinal data collected from 294 respondents who became
      homeless in 1992 and were followed for approximately two years, we find that a
      history of full-time work is the best predictor of whether a woman will find full
      time employment in the aftermath of an episode of homelessness. Even an extensive
      history of part-time or informal work was not predictive of finding employment
      after leaving a homeless shelter. A woman's level of depressive symptomatology at
      the onset of homelessness predicted her strategy in dealing with the shelter
      bureaucracy. Women with full-time work histories who experienced high levels of
      depressive moods at the onset of a shelter episode were likely to leave the
      shelter quickly. Those with lower levels of depressive symptomatology stayed and
      were more likely than others to complete an education or job training program.
      Both types of women with full-time work histories were more likely than others to
      find full-time employment after a homeless episode. These findings suggest that
      policy makers must focus on providing full-time, and not part-time, work for
      impoverished mothers and take depressive symptomatology into account when
      offering assistance to homeless mothers.

PMID- 11459368
TI  - Food insufficiency and the physical and mental health of low-income women.
AB  - Poor women with children are disproportionately represented among the food
      insufficient. Recent research has linked food insufficiency with dietary
      deficiencies, but further research linking this problem to health and mental
      health problems is needed to inform health and social policy. We analyzed the
      relationship between food insufficiency and physical and mental health in a
      random sample of 724 single women who were welfare recipients in February, 1997.
      Food insufficiency was significantly associated with poor or fair self-rated
      health and physical limitations, and with respondents' meeting DSM-III-R criteria
      for recent major depression. Although the cross-sectional design of this study
      precludes causal inference, these findings add to a growing body of evidence that
      food insufficiency is associated with serious adverse physical and mental health
      consequences.

PMID- 11459369
TI  - The influence of patterns of welfare receipt during the child-rearing years on
      later physical and psychological health.
AB  - This study examined interrelations among welfare receipt, social integration, and
      later physical and mental health in a cohort of African American mothers from the
      Woodlawn neighborhood on the south side of Chicago. These women (N = 681) have
      been followed prospectively from 1966-67 to 1997-98. Findings indicate that
      receiving welfare during the child-rearing stage of life is related to both
      social integration and later health, with those who had received welfare in young
      to middle adulthood being more socially isolated and having more health problems
      twenty to thirty years later. Findings provided no support for the hypothesis
      that social integration mediated the relationship between welfare receipt and
      later physical and psychological health problems. Welfare receipt had a direct
      detrimental effect on later health outcomes. Attending church regularly was
      protective for later physical and psychological health. The relationship between
      early welfare and later health remained even when the women's current poverty was
      added to the model.

PMID- 11459370
TI  - Post-Welfare employment and psychological well-being.
AB  - Current public assistance policies are removing many recipients from the welfare
      rolls, regardless of their income level. This article examines the post
      assistance well-being of a stratified probability sample of 426 "able-bodied"
      women and men who lost cash benefits when Michigan terminated its General
      Assistance program in 1991. The relationship of demographic, human capital, and
      psychological resource variables to employment status, depressive symptomatology
      and life satisfaction is examined utilizing two panels of survey data, collected
      approximately one and two years after the program ended. Findings demonstrate
      that personal mastery is related to employment status and risk of depression, and
      sense of burden is linked to both psychological outcomes, controlling for
      relevant demographic and human capital variables. Gender is related to risk of
      depression; however, its relation to employment is dependent on the presence of
      children in the household. Steady employment is positively associated with
      psychological well-being. Overall, the findings suggest that the majority of
      former recipients faced employment difficulties and psychological hardship, and
      that services should be targeted to subgroups of former recipients with
      particular risk factors.

PMID- 11459371
TI  - Foreward: mental health of poor women in an era of devolution.

PMID- 11459372
TI  - Effect of recurrent laryngeal nerve paralysis on superior laryngeal nerve
      afferents during evoked vocalization.
AB  - We tested the hypothesis that vocal fold paresis leads to a substantial reduction
      in activity from the internal branch of the superior laryngeal nerve (iSLN)
      during respiration and evoked vocalization. The iSLN afferent activity was
      measured before and after recurrent laryngeal nerve paresis by cold block in
      decerebrate cats during spontaneous respiration and electrically evoked
      vocalization. Response rate patterns of 33 iSLN single units from 11 cats were
      categorized into 5 groups based on responses to vocalization. Only 24% of single
      units during spontaneous respiration and 18% during evoked phonation displayed
      activity pattern changes as a result of paresis. Those fibers affected were
      heterogeneous in discharge pattern, but none of the units that followed voice
      frequency lost this characteristic when the motor nerve was cooled. The relative
      insensitivity of iSLN activity to motor paralysis suggests that the receptors
      studied are coupled to tissue such that passive interaction rather than active
      muscular contraction is the major stimulus.

PMID- 11459373
TI  - Internal superior laryngeal nerve afferent activity during respiration and evoked
      vocalization in cats.
AB  - The purpose of this project was to identify and categorize patterns of activity
      of the internal branch of the superior laryngeal nerve during vocalization evoked
      by midbrain stimulation in cats anesthetized with alpha-chloralose. Unit activity
      was isolated from the cut distal end of the internal branch of the superior
      laryngeal nerve by means of floating bipolar electrodes that retained their
      contact with nerve fibers despite movement due to vocalization. The phases of
      respiration and vocalization were determined with a diaphragm electromyogram, a
      photoglottogram, and a microphone recording. Five groups of discrete afferent
      activities were defined according to relationships between the spike activity and
      the phases of vocalization. Group 1 cell activity peaked just before phonation,
      during expiratory airflow (n = 26). Group 2 cells (n = 19) followed a vocal fold
      vibratory pattern during phonation. Group 3 cell activity (n = 6) peaked during
      phonation, but did not follow vocal fold vibration. Group 4 cells (n = 3) were
      active during inspiration between phonations. Group 5 cells (n = 4) showed both
      inspiratory and expiratory modulation. These results indicate that laryngeal
      afferent activity responds to phonation-specific events during vocalization. This
      stereotyped afferent information might be used by the central nervous system to
      modulate vocalization.

PMID- 11459374
TI  - Acute sickness behaviour: an immune system-to-brain communication?

PMID- 11459375
TI  - Non-disabled cases in a national survey.
AB  - BACKGROUND: Lifetime and 12-month prevalence estimates of mental disorders
      consistently reported in large-scale community surveys have met with deserved
      scepticism. A crucial variable is the extent to which people who are considered
      cases are also disabled by their symptoms. In a national population survey, we
      hypothesized that an administratively significant proportion of persons with
      anxiety or depressive disorders according to ICD-10 and DSM-IV would report no
      disability. METHODS: Interviews were sought on a nationally representative sample
      of people aged 18 and over across Australia. The Composite International
      Diagnostic Interview on laptop (CIDI-A) was used by professional survey
      interviewers to identify persons meeting ICD-10 or DSM-IV criteria for anxiety or
      depressive disorders in the previous 4 weeks, together with self-reported data on
      associated disability and medical consultations for the same period. RESULTS: In
      an achieved sample of 10,641 persons (response rate = 78%), no disability in
      daily life was reported by 28% of persons with an anxiety disorder and 15% with a
      depressive disorder by ICD-10 criteria; and by 20.4% and 13.9% respectively by
      DSM-IV. Non-disabled respondents had lower scores on two measures of
      psychological distress and markedly lower rates for having consulted a doctor for
      their symptoms. CONCLUSION: The ICD-10 and DSM-IV criteria for anxiety and
      depressive disorders, when applied to the information on symptoms elicited by the
      CIDI-A, inadequately discriminate between people who are and are not disabled by
      their symptoms. There may be a group of highly symptomatic people in the general
      population who tolerate their symptoms and are not disabled by them.

PMID- 11459376
TI  - Psychiatric bed utilization: 1896 and 1996 compared.
AB  - BACKGROUND: The 1896 and 1996 populations of North West Wales are similar in
      number, ethnic and social mix and rurality, enabling a study of the comparative
      incidence and prevalence of service utilization over the course of a century.
      METHODS: We collected records on all psychiatric admissions from North-West Wales
      in 1894-1896 and 1996. These were assessed and diagnosed by the responsible
      sector area consultant. RESULTS: The data reveal substantially more patients
      admitted for all diagnoses in 1996. even when comparisons are restricted to
      detained patients. The incidence of hospitalization by detention for
      schizophrenia is slightly lower 1996 than in 1896 but the incidence of
      hospitalization is higher now than in 1996. The incidence of hospitalization by
      detention for non-affective disorder psychoses is the same in both 1896 and 1996
      but there is a doubling of incidence of hospitalization. The incidence of
      hospitalization for bipolar disorders is similar in the two periods. Modern
      mental health services admit large numbers of personality disordered patients,
      where none were admitted 100 years ago. CONCLUSIONS: Factors general to changing
      health care and expectations and others specific to mental health would appear to
      have led to the increase in rates of admissions observed in the modern period.

PMID- 11459377
TI  - One-month prevalence of depression and other DSM-IV disorders among young adults.
AB  - BACKGROUND: We aimed to provide prevalence data on depression and other current
      mental disorders, impairment, need of psychiatric care and use of mental health
      services among young adults. METHODS: Based on a semi-structured clinical
      interview, current DSM-IV disorders, impairment, need of psychiatric care and use
      of mental health services were evaluated in a sample of 20-24-year-old young
      urban adults (N = 245), mean age 21.8, screened from a baseline population of
      706. One-month prevalence estimates for disorders were calculated by the double
      sampling method, using various additional criteria to identify cases. RESULTS:
      One in four young adults (23.8%) suffered from a current mental disorder, the
      most prevalent being depressive (10.8%), anxiety (6.9%), substance use (6.2%) and
      personality disorders (6.0%). Prevalence estimates varied substantially according
      to the use of additional diagnostic criteria. Impairment (GAF < 61) together with
      DSM-IV symptom criteria produced an overall disorder prevalence of 10.3%, and
      5.5% for depression. Prevalences were higher for females than males, except for
      alcohol abuse and personality disorders. Current co-morbidity was found in 39% of
      subjects with any disorder, and in more than half of those with depression. One
      third of subjects with a current disorder reported an associated contact with
      psychiatric services and 16% had an ongoing contact. CONCLUSIONS: Our findings
      support the use of additional criteria to produce clinically relevant prevalence
      data. Co-morbidity should receive special attention due to its amplification of
      both need for psychiatric care and severity of impairment. Finally, our results
      show disturbed young adults to be severely undertreated.

PMID- 11459378
TI  - Religion as a cross-cultural determinant of depression in elderly Europeans:
      results from the EURODEP collaboration.
AB  - BACKGROUND: The protective effects of religion against late life depression may
      depend on the broader sociocultural environment. This paper examines whether the
      prevailing religious climate is related to cross-cultural differences of
      depression in elderly Europeans. METHODS: Two approaches were employed, using
      data from the EURODEP collaboration. First, associations were studied between
      church-attendance, religious denomination and depression at the syndrome level
      for six EURODEP study centres (five countries, N = 8398). Secondly, ecological
      associations were computed by multi-level analysis between national estimates of
      religious climate, derived from the European Value Survey and depressive
      symptoms, for the pooled dataset of 13 EURODEP study centres (11 countries, N =
      17,739). RESULTS: In the first study, depression rates were lower among regular
      church-attenders, most prominently among Roman Catholics. In the second study,
      fewer depressive symptoms were found among the female elderly in countries,
      generally Roman Catholic, with high rates of regular church-attendance. Higher
      levels of depressive symptoms were found among the male elderly in Protestant
      countries. CONCLUSIONS: Religious practice is associated with less depression in
      elderly Europeans, both on the individual and the national level. Religious
      practice, especially when it is embedded within a traditional value-orientation,
      may facilitate coping with adversity in later life.

PMID- 11459379
TI  - Cultural influences on the prevalence of common mental disorder, general
      practitioners' assessments and help-seeking among Punjabi and English people
      visiting their general practitioner.
AB  - BACKGROUND: Culture influences symptom presentation and help-seeking and may
      influence the general practitioner's assessment. METHODS: We recruited Punjabi
      and English GP attenders to a two-phase survey in London (UK) using the Amritsar
      Depression Inventory and the General Health Questionnaire as screening
      instruments. The Clinical Interview Schedule was the criterion measure. General
      practitioners completed Likert assessments. RESULTS: The second phase was
      completed by 209 Punjabi and 180 English subjects. The prevalence of common
      mental disorders was not influenced by culture. Punjabi cases more often had
      'poor concentration and memory' and 'depressive ideas' but were not more likely
      to have somatic symptoms. General practitioners were more likely to assess
      Punjabis with common mental disorder as having 'physical and somatic' symptoms or
      'sub-clinical disorders'. Punjabi cases with depressive ideas were less likely to
      be detected compared with English ones. In comparison to English men, English
      women were under-detected by Asian general practitioners. Help-seeking English
      subjects were more likely to be correctly identified as cases. CONCLUSIONS: The
      prevalence of common mental disorders and somatic symptoms does not differ across
      cultures. Among English subjects, general practitioners were more likely to
      identify correctly pure psychiatric illness and mixed pathology; but Punjabi
      subjects with common mental disorders were more often assessed as having 'sub
      clinical disorders' and 'physical and somatic' disorders. English women were less
      well detected than English men. English help-seeking cases were more likely to be
      detected.

PMID- 11459380
TI  - The influence of the economic and social environment on deliberate self-harm and
      suicide: an ecological and person-based study.
AB  - BACKGROUND: Geographic variations in the incidence of deliberate self-harm (DSH)
      and suicide have been shown to be associated with area-based measures of socio
      economic deprivation and social fragmentation. Previous studies have been subject
      to methodological limitations. None has investigated whether ecological
      associations are reflected in characteristics of individuals involved in suicidal
      behaviour. METHODS: DSH patients presenting to a general hospital between 1985
      and 1995 and suicides (including open verdicts) from the same catchment area were
      studied. Mean annual rates of DSH and suicide by gender were calculated for
      electoral wards. The wards were amalgamated into 20 groups according to their
      ranking for socio-economic deprivation (Townsend) and social fragmentation
      scores. Associations of these variables with DSH and suicide rates were
      investigated. Characteristics of DSH patients living in ward groups with the
      highest and lowest socio-economic deprivation and social fragmentation scores
      were compared. RESULTS: Socio-economic deprivation was associated with DSH rates
      among males (r = 0.89) and females (r = 0.87). After controlling for social
      fragmentation the associations remained relatively strong, particularly in young
      males. Associations with social fragmentation in both genders (males, r = 0.83;
      females, r = 0.86) were attenuated after controlling for socio-economic
      deprivation. For suicide, the only significant association was with socio
      economic deprivation in males (r = 0.79), but this was attenuated after
      controlling for social fragmentation. The characteristics of individual DSH
      patients reflected those of the areas where they lived. CONCLUSIONS: Reducing
      socio-economic deprivation and its associated problems may be an important
      strategy in the prevention of suicidal behaviour, especially in young men.

PMID- 11459381
TI  - Suicides and serious suicide attempts: two populations or one?
AB  - BACKGROUND: Few studies have examined the extent to which populations of suicides
      and attempted suicides are similar, or different. This paper compares suicides
      and serious suicide attempts in terms of known risk factors for suicidal
      behaviour. METHODS: Using case-control methodology, risk factors for suicidal
      behaviour were examined in 202 individuals who died by suicide, 275 individuals
      who made medically serious suicide attempts and 984 randomly selected control
      subjects. Based on data from significant others, measures used spanned
      sociodemographic factors, childhood experiences, psychiatric morbidity and
      psychiatric history, exposure to recent stressful life events and social
      interaction. RESULTS: Multiple logistic regression identified the following risk
      factors that were common to suicide and serious suicide attempts: current mood
      disorder; previous suicide attempts; prior outpatient psychiatric treatment;
      admission to psychiatric hospital within the previous year; low income; a lack of
      formal educational qualifications; exposure to recent stressful interpersonal,
      legal and work-related life events. Suicides and suicide attempts were
      distinguished in the following ways: suicides were more likely to be male (OR =
      1.9, 95% CI 1.1, 3.2); older (OR = 1.03, 95% CI 1.02, 1.04); and to have a
      current diagnosis of non-affective psychosis (OR = 8.5, 95% CI 2.0, 35.9).
      Suicide attempts were more likely than suicides to have a current diagnosis of
      anxiety disorder (OR = 3.5, 95% CI 1.6, 7.8) and to be socially isolated (OR =
      2.0, 95% CI 1.2, 3.5). These findings were confirmed by discriminant function
      analysis, which identified two functions that described the three subject groups:
      the first function discriminated the two suicide groups from control subjects on
      a dimension corresponding to risk factors for suicide; the second function
      discriminated suicide from suicide attempt subjects on a series of factors
      including gender, non-affective psychosis and anxiety disorder. CONCLUSIONS:
      Suicides and medically serious suicide attempts are two overlapping populations
      that share common psychiatric diagnostic and history features, but are
      distinguished by gender and patterning of psychiatric disorder.

PMID- 11459382
TI  - Effects of pregnancy and delivery on the availability of plasma tryptophan to the
      brain: relationships to delivery-induced immune activation and early post-partum
      anxiety and depression.
AB  - BACKGROUND: There is now evidence that the availability of plasma tryptophan is
      decreased during pregnancy and the puerperium and also in patients with major
      depression and inflammation. The aims of the present study were to examine: (i)
      the effects of pregnancy and delivery on plasma tryptophan and the amino acids
      known to compete for the same cerebral uptake mechanism (CAAs), valine, leucine,
      tyrosine, phenylalanine and isoleucine; (ii) the relationships between the
      availability of plasma tryptophan and postpartum depression or anxiety; and (iii)
      the relationships between the availability of plasma tryptophan to the brain and
      inflammatory markers, such as serum interleukin-6 (IL-6), interleukin-1 receptor
      antagonist (IL-1RA) and the leukaemia inhibitory factor receptor (LIF-R).
      METHODS: The above variables were measured in 13 healthy non-pregnant and in 98
      pregnant women 3 to 6 days before delivery and 1 and 3 days after delivery. On
      each occasion the parturient women completed the state version of Spielberger
      State-Trait Anxiety Inventory (STAI) and the Zung Depression Rating Scale (ZDS).
      RESULTS: Plasma tryptophan and the tryptophan/CAA ratio were significantly lower
      at the end of term and after delivery than in the plasma of non-pregnant, healthy
      women. The tryptophan/CAA ratio was significantly lower in the early puerperium
      than at the end of term. There were no significant relationships between the
      availability of plasma tryptophan and either post-partum depression or changes in
      the STAI or ZDS scores in the early puerperium. The changes in the tryptophan/CAA
      ratio from the end of term to the early puerperium were significantly and
      inversely related to serum IL-6, IL-IRA and LIF-R. CONCLUSIONS: The results show
      that the reduction in the availability of plasma tryptophan from the end of term
      to the early puerperium is related to immune activation; and that the lowered
      availability of plasma tryptophan is not related either to depressive or anxiety
      symptoms in the early puerperium or to post-partum depression ensuing some months
      later.

PMID- 11459383
TI  - Life events, difficulties and onset of depressive episodes in later life.
AB  - BACKGROUND: The importance of stressful life events and long-term difficulties in
      the onset of episodes of unipolar depression is well established for young and
      middle-aged persons, but less so for older people. METHOD: A prospective case
      control study was nested in a large community survey of older people. We
      recruited 83 onset cases during a 2-year period starting 2 1/2 years after the
      survey, via screening (N = 59) and GP monitoring (N = 24), and 83 controls, a
      random sample from the same survey population. We assessed depression with the
      PSE-10 and life stress exposure with the LEDS. RESULTS: Risk of onset was
      increased 22-fold by severe events and three-fold by ongoing difficulties of at
      least moderate severity. Severe events accounted for 21% of all episodes but
      ongoing difficulties for 45%. The association of onset with life stress, often
      health-related such as death, major disability and hospitalization of subject or
      someone close, was most pronounced in the cases identified by screening. While a
      clear risk threshold for events was found between threat 2 and 3 (on a scale of 1
      4), the risk associated with difficulties increased more gradually with severity
      of difficulty. Compared with controls, severe events involved a larger risk for
      cases without a prior history of depression (OR = 39.48) than for cases with (OR
      = 8.86). The opposite was found for mild events (OR = 2.94 in recurrent episodes;
      OR = 1.09 in first episodes). The impact of ongoing difficulties was independent
      of severity of episode and history of depression. CONCLUSION: Although the nature
      of life stress in later life, in particular health-related disability and loss of
      (close) social contacts, is rather different from that in younger persons, it is
      a potent risk factor for onset of a depressive episode in old age. Severe events
      show the largest relative risk, but ongoing difficulties account for most
      episodes. The association of severe events with onset tends to be stronger in
      first than in recurrent episodes. Mild events can trigger a recurrent episode but
      not a first one.

PMID- 11459384
TI  - Cognitive therapy, nutritional therapy and their combination in the treatment of
      bulimia nervosa.
AB  - BACKGROUND: This study compared the effectiveness of cognitive therapy (CT),
      nutritional therapy (NT), the combination of cognitive and nutritional therapy
      (CNT), against a control condition of support group (SG) in the treatment of
      bulimia nervosa. METHODS: One hundred female out-patients who fulfilled DSM-III-R
      criteria for bulimia nervosa were randomized to the four treatment groups. NT and
      CT were designed to cover different areas with minimal overlap, and CNT provided
      all of the features of both of these treatments. The control condition was
      conducted in a group self-help format. Each of the treatments lasted 14 weeks.
      RESULTS: All three active treatments as well as SG produced significant decreases
      in binge/vomit episodes. Intent-to-treat analysis found CNT and CT to be
      significantly more effective than SG in retaining subjects in treatment and
      completion of study, as well as in producing greater improvements in
      dysfunctional attitudes and self-control. CNT was superior to SG in achieving
      abstinence from bulimic behaviour. NT was superior to SG only in increase of self
      control. Logistic regression found that the cognitive component, whether given
      alone or in conjunction with NT, and higher pre-treatment self-control scores
      were significant predictors for both completion of study and abstinence.
      CONCLUSION: CT (either alone, or in combination with nutritional therapy) remains
      the treatment of choice for bulimia nervosa. A treatment escalation approach
      should be tested for the treatment of bulimia with the more intensive and less
      widely available CT (with or without nutritional counselling) offered after
      patients have failed the less intensive and more widely available support group
      treatment.

PMID- 11459385
TI  - Long-term outcome of anorexia nervosa in a prospective 21-year follow-up study.
AB  - BACKGROUND: Given our poor understanding of the very long-term course of anorexia
      nervosa. many questions remain regarding the potential for recovery and relapse.
      The purpose of the present study was to investigate long-term outcome and
      prognosis in an anorexic sample 21 years after the initial treatment. METHOD: A
      multidimensional and prospective design was used to assess outcome in 84 patients
      9 years after a previous follow-up and 21 years after admission. Among the 70
      living patients, the follow-up rate was 90%. Causes of death for the deceased
      patients were obtained through the attending physician. Predictors of a poor
      outcome at the 21-year follow-up were selected based on the results of a previous
      12-year follow-up of these patients. RESULTS: Fifty-one per cent of the patients
      were found to be fully recovered at follow-up, 21% were partially recovered and
      10% still met full diagnostic criteria for anorexia nervosa. Sixteen per cent
      were deceased, due to causes related to anorexia nervosa. The standardized
      mortality rate was 9.8. The three groups also showed significant differences in
      psychosocial outcome. A low body mass index and a greater severity of social and
      psychological problems were identified as predictors of a poor outcome.
      CONCLUSIONS: Recovery is still possible for anorexic patients after a period of
      21 years. On the other hand, patients can relapse, becoming symptomatic again
      despite previously achieving recovery status. Only a few patients classified as
      having a poor outcome were found to seek any form of treatment, therefore, it is
      recommended that these patients should be monitored regularly and offered
      treatment whenever possible.

PMID- 11459386
TI  - Long-term outcome of panic disorder with agoraphobia treated by exposure.
AB  - BACKGROUND: There is a paucity of long-term outcome studies of panic disorder
      that exceed a 2-year follow-up. The aim of the study was to evaluate the long
      term follow-up of patients with panic disorder with agoraphobia treated according
      to a standardized protocol. METHODS: A consecutive series of 200 patients
      satisfying the DSM-IV criteria for panic disorder with agoraphobia was treated in
      an out-patient clinic with behavioural methods based on exposure homework. One
      hundred and thirty-six patients became panic free after 12 sessions of
      psychotherapy and 132 were available for follow-up. A 2- to 14-year (median = 8
      years) follow-up was performed. Survival analysis was employed to characterize
      the clinical course of patients. RESULTS: Thirty-one of the 132 patients (23%)
      had a relapse of panic disorder at some time during follow-up. The estimated
      cumulative percentage of patients remaining in remission was 93.1 after 2 years,
      82.4 after 5 years, 78.8 after 7 years and 62.1 after 10 years. Such
      probabilities increased with younger age, and in the absence of a personality
      disorder, of high pre-treatment levels of depressed mood, of residual agoraphobic
      avoidance after exposure, and of concurrent use of benzodiazepines and
      antidepressant drugs. CONCLUSIONS: The findings suggest that exposure treatment
      can provide lasting relief to the majority of patients with panic disorder and
      agoraphobia. Disappearance of residual and subclinical agoraphobic avoidance, and
      not simply of panic attacks, should be the aim of exposure therapy.

PMID- 11459387
TI  - Long-term outcome of social phobia treated by exposure.
AB  - BACKGROUND: There is very little information on long-term follow-up of social
      phobia. METHODS: A consecutive series of 70 patients satisfying the DSM-IV
      criteria for social phobia was treated in an out-patient clinic with behavioural
      methods based on exposure homework. Forty-five patients were judged to be
      remitted after eight individual sessions of psychotherapy. A 2 to 12 year (median
      = 6 years) follow-up was performed. Survival analysis was selected to
      characterize the clinical course of patients. Assessments were performed before
      treatment, at the end of therapy, after 1 year, and subsequently on a yearly
      basis, and utilized selected items of Paykel's Clinical Interview for Depression.
      RESULTS: Six of the 45 patients (13%) had a relapse of social phobia at some time
      during follow-up. The estimated cumulative percentage of patients remaining in
      remission was 98 after 2 years, 85 after 5 years and 85 after 10 years. Such
      probabilities increased in the absence of a personality disorder, of residual
      social phobic avoidance after exposure, and of concurrent use of benzodiazepines.
      CONCLUSIONS: The findings suggest that, even though one patient out of three is
      unable to complete treatment or does not benefit sufficiently from it, exposure
      treatment can provide lasting effects to the majority of patients with social
      phobia. Disappearance of residual, subclinical social phobic avoidance appears to
      be the target of treatment.

PMID- 11459388
TI  - The association between obstetric complications and childhood-onset
      schizophrenia: a replication study.
AB  - BACKGROUND: Many previous studies have shown that individuals who develop
      schizophrenia in adult life are more likely than normal controls to have a
      history of obstetric complications (OCs) at birth. However, little attention has
      been paid to the involvement of OCs in the risk of developing childhood-onset
      schizophrenia (COS). In our earlier report, we found an association between OCs
      and the development of COS. In this study, we determined whether the association
      could be replicated in another, independent set of patients with COS. METHODS:
      OCs, birth weight and gestational age were retrospectively assessed in 35
      children, aged between 14 and 15 years old (average 15.4 years), who met the DSM
      III-R criteria for schizophrenia, and in age- and gender-matched controls
      (children with anxiety disorders). RESULTS: The COS patients showed significantly
      greater scores in all of the three measures of OCs according to the Parnas et al.
      scale compared to controls. Moreover, individuals exposed to OCs were about 3.2
      times (odds ratio = 3.22; 95% confidence interval, 1.1-9.8) more likely to
      develop schizophrenia than those without a history of OCs. The mean birth weight
      was significantly lower in schizophrenics than in controls (P < 005). The
      frequency of prematurity signs with weight < 2500 g was significantly higher in
      schizophrenics than in controls (P < 0.05). CONCLUSION: Repeatedly reported
      association between OCs and adult-onset schizophrenia have also been demonstrated
      in patients with COS. This suggests that there may be a continuity between
      childhood- and adult-onset schizophrenia.

PMID- 11459389
TI  - Different trait markers for schizophrenia and bipolar disorder: a neurocognitive
      approach.
AB  - BACKGROUND: The aim of this study was to assess visual information processing and
      cognitive functions in unaffected siblings of patients with schizophrenia,
      bipolar disorder and control subjects with a negative family history. METHODS:
      The siblings of patients with schizophrenia (N = 25), bipolar disorder (N = 20)
      and the controls subjects (N = 20) were matched for age, education, IQ, and
      psychosocial functioning, as indexed by the Global Assessment of Functioning
      scale. Visual information processing was measured using two visual backward
      masking (VBM) tests (target location and target identification). The evaluation
      of higher cognitive functions included spatial and verbal working memory,
      Wisconsin Card Sorting Test, letter fluency, short/long delay verbal recall and
      recognition. RESULTS: The relatives of schizophrenia patients were impaired in
      the VBM procedure, more pronouncedly at short interstimulus intervals (14, 28, 42
      ms) and in the target location task. Marked dysfunctions were also found in the
      spatial working memory task and in the long delay verbal recall test. In
      contrast, the siblings of patients with bipolar disorder exhibited spared
      performances with the exception of a deficit in the long delay recall task.
      CONCLUSIONS: Dysfunctions of sensory-perceptual analysis (VBM) and working memory
      for spatial information distinguished the siblings of schizophrenia patients from
      the siblings of individuals with bipolar disorder. Verbal recall deficit was
      present in both groups, suggesting a common impairment of the fronto-hippocampal
      system.

PMID- 11459390
TI  - Time, memory and the heritability of major depression.
AB  - OBJECTIVE: Although family, twin and adoption studies have suggested that
      lifetime major depression (MD) is a heritable condition, nearly all these studies
      have relied for the diagnosis on long-term human memory, which is fallible and
      potentially biased. Could the estimates of heritability of MD be biased by the
      well-demonstrated genetic influences on memory? METHODS: Both members of 858
      female-female twin pairs from a population-based registry were personally
      interviewed at least three times over 9 years. The interview assessed a history
      of depressive onsets and recoveries in the last year to the nearest month. We
      examine heritability of MD using four recall intervals: last year, last 6 months,
      last 3 months and current month. RESULTS: Examining the occurrence of one or more
      depressive episodes across all three interviews, heritabilities of MD (95% CI)
      for the four time periods were: 0.41 (0.27-0.54), 0.41 (0.26-0.55), 0.35 (0.16
      0.52) and 0.34 (0.11-0.55). These heritability estimates did not differ
      significantly from one another. A similar pattern was found if heritability was
      assessed for the number of interviews in which criteria for MD were met.
      CONCLUSION: Modelling results suggest that the heritability of MD was not
      influenced by the duration of the required recall. Genetic influences on human
      recall do not appear to contribute substantially to estimated heritability of MD.

PMID- 11459391
TI  - Electro-convulsive therapy practices in the community.
AB  - BACKGROUND: Controlled studies have demonstrated that variations in electro
      convulsive therapy (ECT) technique impacts on efficacy and cognitive side
      effects. However, there is little information on the extent of variation in how
      ECT is practiced in community settings in the United States. METHODS: A survey of
      practice patterns was conducted at ECT facilities in the greater New York City
      metropolitan area. RESULTS: The 59 facilities varied considerably in many aspects
      of ECT practice, often clearly departing from the standards in the field. The
      more intensive the form of ECT used at facilities, the less likely was cognitive
      status assessed following the treatment course. CONCLUSION: There is marked
      variability in the nature of ECT practices in community settings. The extent to
      which this variability impacts on the benefits and risks of ECT needs to be
      examined.

PMID- 11459392
TI  - Changes in rates of suicide by car exhaust asphyxiation in England and Wales.
AB  - BACKGROUND: Self-asphyxiation using car exhaust gas is a common method of suicide
      in England and Wales, particularly in young males. The introduction of catalytic
      converters has reduced the toxicity of car exhausts. The main aims of the study
      were: to seek evidence of a fall in car exhaust suicides in the general
      population and in age and gender groups; to relate any fall to changes in car
      exhaust systems, particularly since legislation on car exhaust emissions in 1993;
      and to examine rates of suicide by other methods for evidence of method
      substitution. METHODS: Population study in England and Wales using national
      suicide statistics for 1987 to 1998. RESULTS: There was a fall in suicide by car
      exhaust asphyxiation in all age and gender groups. This change was most marked
      after 1993. The overall population suicide rate (all methods) also fell but there
      was no overall change in suicides by young males or females. In these groups
      suicide by hanging increased. CONCLUSIONS: Legislation on catalytic converters
      appears to have contributed to a fall in car exhaust suicides. However, the
      effect on overall suicide rates in young people has been reduced by method
      substitution.

PMID- 11459393
TI  - Organ donation and family decision-making within the Spanish donation system.
AB  - This study analyses the variables associated with the decisions made by families
      of potential organ donors to give or deny consent for the extraction of organs.
      Different indicators were recorded in 68 cases of family interview for petition
      of consent carried out in 13 Spanish hospitals. Those variables showing the
      strongest relation with family decision (donation/refusal of consent) are
      knowledge shown by the family about the deceased's wishes with regard to donation
      (p<0.001), family relationship climate (p<0.01), expression of family's
      satisfaction level with medical attention received (p<0.01) and number of
      relatives present at the consent request interview (p<0.01). Logistic regression
      on family decision with considered variables correctly predicted relatives' final
      choice in 98.4% of cases. In turn, multivariate exploratory analysis highlights a
      potential association between the expression of the deceased's wishes and several
      concurrent variables in the process (satisfaction with personal treatment and
      medical attention received, emotional reactions in the interviews of notification
      of death and consent request). It also shows that patterns of reaction and family
      participation in this process may vary according to the sex of the deceased
      relative. Results suggest that both educational efforts devoted to promoting a
      positive attitude toward donation in the general population and the training of
      health professionals involved in the generation of organs may be key factors in
      reducing organ shortage.

PMID- 11459394
TI  - Children's emotional and behavioural well-being and the family environment:
      findings from the Health Survey for England.
AB  - Recent trends towards diversity in family structure have posed important
      challenges for traditional social theories on the family. This critical debate
      has not, however, had much influence on policy discussions of the impact of
      diverse family structures on children's psychological health, where two-parent
      families are presumed ideal. In 1997, the annual Health Survey for England
      focussed on the health of children and young people. The Strengths and
      Difficulties Questionnaire (SDQ), used to assess children's psychological health,
      was administered to the parents of 5705 children aged 4-15 using a self
      completion booklet. The effect of family structure, socio-economic indicators,
      parental working status and parental psychological status on children's
      psychological health was explored using multi-variate logistic regression models.
      Findings indicated that the high prevalence of psychological morbidity among
      children of lone-mothers was a consequence of socio-economic effects.
      disappearing when benefits receipt, housing tenure and maternal education were
      taken into account. Socio-economic factors did not, however, explain the higher
      proportion of psychological morbidity among children with stepparents, or the
      strong relationship between parents' and children's psychological morbidity.

PMID- 11459395
TI  - Debt, social disadvantage and maternal depression.
AB  - Depression is common among women with young children, and is strongly associated
      with financial adversity. Debt is a common feature of such adversity, yet its
      relationship with depression has not been examined before. We have used
      longitudinal data, collected over six months, on 271 families with young
      children, to examine this relationship. Multiple regression was used to identify
      independent predictors of the total Edinburgh Post-natal Depression Scale score
      from a range of socioeconomic, demographic, social support and child health
      related variables. Worry about debt was the strongest independent socioeconomic
      predictor of the depression score at both initial and follow-up occasions. To
      account for the possibility of reverse causation, i.e. depression causing worry
      about debt, alternative regression models are reported which show that owing
      money by itself predicts depression and earlier debt worries predicts depression
      six months later. We were unable to show that earlier debt worries independently
      predicted subsequent depression scores after the initial depression score had
      been taken into account in the analysis. Although debt has not been shown to be
      an independent prospective predictor of depression, our results suggest it has a
      central place in the association between socioeconomic hardship and maternal
      depression. Evidence from qualitative studies on poverty and from studies on the
      causes of depression support this hypothesis. The implications for policy are
      that strategies to enable families to control debt should be an explicit part of
      wider antipoverty measures which are designed to reduce depression and
      psychological distress among mothers of young children.

PMID- 11459396
TI  - Chinese seniors' perspectives on end-of-life decisions.
AB  - Making end-of-life decisions is a painful and difficult process; one that can be
      intensified by cultural differences between physicians and their patients. The
      objective of this study was to examine attitudes of Chinese seniors towards end
      of-life decisions. We conducted a qualitative survey in a Chinese community
      centre in Toronto, Canada. Face-to-face interviews, in Cantonese, were conducted
      with 40 Chinese seniors 65 years of age or older. Respondents based their end-of
      life decision making on the following factors: hope, suffering and burden, the
      future, emotional harmony, the life cycle, respect for doctors, and the family.
      Respondents rejected advance directives. Respondents' attitudes toward end-of
      life decision making can be understood through the lens of values from
      Confucianist, Buddhist and Taoist traditions. Health care workers can best
      achieve quality end-of-life care--and address the cultural differences that may
      arise--by focusing primarily on understanding the perspectives of patients and
      their families, and by continually striving for balanced and open communication
      at all stages of the caregiving process.

PMID- 11459397
TI  - Perceptions of illness causation among new referrals to a community mental health
      team: "explanatory model" or "exploratory map"?
AB  - The health beliefs of people suffering from mental health problems are important.
      Such beliefs have been identified as key factors in models of health and illness
      behaviour, and may therefore indirectly influence clinical outcome. In addition,
      the increasing move towards patient-centred health care suggests that such
      beliefs need to be identified if a patient's perspective of his or her illness is
      to be addressed in the care process. Past research on health beliefs surrounding
      depression have concentrated on identifying "explanatory models" among the
      general community or among people who already have an established diagnosis of
      depression. This paper describes the content and status of health beliefs among
      people who are in the process of receiving a diagnosis. In-depth interviews were
      carried out with new referrals to a community mental health team (CMHT).
      Individuals expressed a variety of perceived causes throughout the interview.
      Beliefs were therefore characterised as changeable. It is argued that the concept
      of an "explanatory model" is too fixed to fully convey the fluid status of
      beliefs among this patient group. The concept of an "exploratory map" is
      suggested as a replacement. Such maps outline the avenues of thought which
      individuals explored when attempting to understand why they were currently
      experiencing particular psychological problems. The strength and persistence of
      beliefs is discussed in relation to both theoretical and clinical implications.

PMID- 11459398
TI  - The socioeconomic position of employed women, risk factors and mortality.
AB  - Many studies have demonstrated the graded association between socioeconomic
      position and health. Few of these studies have examined the cumulative effect of
      socioeconomic position throughout the lifecourse, and even fewer have included
      women. Those that have explored gender differences affirm the importance of
      studying the factors that predict women and men's health separately. This study
      addresses the associations between cross-sectional and longitudinal socioeconomic
      position, risk factors for cardiovascular disease and mortality from various
      causes. Analyses are based on data from a cohort of working Scottish women
      recruited between 1970 and 1973. Five socioeconomic measures were explored in
      relation to diastolic blood pressure, plasma cholesterol concentration, body mass
      index, forced expiratory volume in 1 s (FEV1). amount of recreational exercise
      taken, cigarette smoking and alcohol consumption. In general, for each of the
      five measures of socioeconomic position, there were significant differences in at
      least one of the age-adjusted physiological risk factors for cardiovascular
      disease (diastolic blood pressure, plasma cholesterol concentration, body mass
      index, FEV1). There were also significant differences in the percentage of
      current cigarette smokers according to different measures of socioeconomic
      position, although this was not the case for the other behavioural risk factors
      for cardiovascular disease (amount of recreational exercise taken, and alcohol
      consumption). Measures of socioeconomic position were also examined in relation
      to cause of death for the women who died before 1 January 1999. After adjusting
      for age and risk factors, a composite measure of lifetime socioeconomic
      experience was a more potent predictor of all cause mortality and mortality from
      cardiovascular disease than other measures of socioeconomic position. It
      therefore seems that conventional measurcs of socioeconomic position, estimated
      at one point in time, do not adequately capture the effects of socioeconomic
      circumstances on the risk of mortality among employed women. Thus, a broader
      range of explanatory factors for mortality differentials than currently exists
      must be considered, and must include consideration of factors operating
      throughout the lifecourse.

PMID- 11459399
TI  - Giving voice to the lifeworld. More humane, more effective medical care? A
      qualitative study of doctor-patient communication in general practice.
AB  - Mishler (The discourse of medicine. The dialectics of medical interviews.
      Norwood, NJ: Ablex), applying Habermas's theory of Communicative Action to
      medical encounters. showed how the struggle between the voice of medicine and the
      voice of the lifeworld fragmented and suppressed patients' multi-faceted,
      contextualised and meaningful accounts. This paper investigates and critiques
      Mishler's premise that this results in inhumane, ineffective medical care. Using
      a more complex data collection strategy, comprising patient interviews, doctor
      interviews and transcribed consultations we show more complex relations than
      emerged from Mishler's analysis. We found four communication patterns across 35
      general practice case studies. When doctor and patient both used the voice of
      medicine exclusively (acute physical complaints) this worked for simple unitary
      problems (Strictly Medicine). When both doctor and patient engaged with the
      lifeworld, more of the agenda was voiced (Mutual Lifeworld) and patients were
      recognised as unique human beings (psychological plus physical problems). Poorest
      outcomes occurred where patients used the voice of the lifeworld but were ignored
      (Lifeworld Ignored) or blocked (Lifeworld Blocked) by doctors' use of voice of
      medicine (chronic physical complaints). The analysis supports the premise that
      increased use of the lifeworld makes for better outcomes and more humane
      treatment of patients as unique human beings. Some doctors switched communication
      strategies in different consultations, which suggests that their behaviour might
      be open to change. If doctors could be sensitised to the importance of dealing
      with the concerns of the lifeworld for patients with chronic physical conditions
      as well as psychological conditions, it might be possible to obtain better care
      for patients. This would require attention to structural aspects of the
      healthcare system to enable doctors to work fully within the patient-centred
      model.

PMID- 11459400
TI  - Variations in general practitioners' views of asthma management in four European
      countries.
AB  - The aim was to identify differences and similarities in views regarding asthma
      management among general practitioners in four European countries (Germany,
      Netherlands, Norway and Sweden), and to explore reasons for suboptimal
      performance. The results are to be used for the development and tailoring of
      educational interventions. Semistructured interviews with 20 GPs in each country
      were conducted and analysed using a phenomenographic approach. The domains of (i)
      general view of asthma, (ii) the doctor-patient relationship in managing asthma,
      and (iii) overall management of asthma (treatment goals and evaluation of
      results) were approached during the interviews. There were different ways of
      experiencing phenomena related to asthma management both within and between the
      four countries. Three general views on asthma were found where different
      perspectives were emphasised: a medical, a 'global' (including community health,
      social and environmental aspects) and a patient's perspective. Within the medical
      perspective, only a few German doctors emphasised a psychological aetiology of
      asthma. The views on the doctor-patient relationship described as
      'authoritarian', 'teaching' or 'empowering' occurred similarly in all countries.
      The majority of the doctors showed confidence in the effectiveness of the
      pharmaceutical treatment of asthma, some doctors were concerned about
      limitations, but only in Germany a few doctors were explicitly critical of the
      values of conventional pharmaceutical treatment. The main treatment goals were
      either conceived as getting the patient symptom-free (Netherlands, Norway, and
      Germany) or to control the inflammatory process (Sweden). Several German and some
      Norwegian doctors expressed the view that patients had to accept the disease and
      learn how to manage it, while a few German doctors aimed at alternative
      treatments of asthma. The existence of qualitatively different ways of
      experiencing asthma management, both in and between countries, calls for
      consideration when trying to implement general evidence-based treatment
      guidelines. A variation of approaches in continuing medical education for GPs is
      needed to address such existing beliefs and conceptions that could sometimes be
      opposed to the content of educational messages.

PMID- 11459401
TI  - The convergence of vulnerable characteristics and health insurance in the US.
AB  - This study defines vulnerability as a multi-dimensional construct, reflected in
      the convergence of predisposing, enabling, and need attributes of risk. Using
      race, income, and self-perceived health status as indicators and based on eight
      rounds of the US 1996 panel of the Medical Expenditure Panel Survey, the study
      examined how the interactions of these vulnerable characteristics affect
      insurance coverage, a critical measure of health care access. The results of the
      study demonstrate insurance coverage does vary with the extent of vulnerability.
      While race and income significantly influence insurance coverage, respectively,
      there was relatively little disparity in insurance due to health status. Between
      race and income, income was a more significant predictor of lack of insurance
      coverage since low-income people regardless of race and health were significantly
      more likely to be uninsured or partially insured. However, it is important to
      note that minorities were disproportionately over-represented in the low-income
      or bad health groups so that any adverse association between income, bad health,
      and insurance status would affect minorities significantly more than whites.
      Among those with insurance, the most vulnerable group, the minority-low-income
      bad health group or those with all the three vulnerability indicators, were most
      likely to be publicly insured. A policy implication is to target limited
      resources on insurance coverage for the more vulnerable groups, those with a
      convergence or cluster of predisposing, enabling, and need attributes of risk.

PMID- 11459402
TI  - Legalized, regulated, but unfunded: midwifery's laborious professionalization in
      Alberta, Canada, 1975-99.
AB  - In 1992, Alberta became the second Canadian province to legalize midwifery. This
      happened even though there were only approximately 20 midwives in practice at the
      time, and despite strong opposition from the medical and nursing professions.
      Between 1992 and 1999. Alberta established a regulatory framework for midwifery
      as a profession but. unlike Ontario and British Columbia, failed to pay midwives
      out of the provincial health care budget. This sent midwifery in Alberta into a
      crisis as many midwives closed their practices. This article first considers why
      midwifery was legalized and then professionalized in Alberta. Our answer
      emphasizes the leading role of state health bureaucrats in promoting midwifery as
      part of the state's challenge to medical dominance. Second. the article addresses
      why midwifery received so little governmental support at the same time that it
      attained professional status. This analysis includes a comparison with how
      midwifery developed in Ontario and British Columbia. Our conclusion is that
      midwifery in Alberta became a victim in the post-1993 period when a new Right
      government set aside bureaucratic initiatives in health care and committed itself
      to major cuts in government spending.

PMID- 11459403
TI  - Shan women and girls and the sex industry in Southeast Asia; political causes and
      human rights implications.
AB  - The human rights abuses which occur during civil conflicts pose special threats
      to the health and lives of women. These can include rape, sexual violence,
      increased vulnerability to trafficking into prostitution, and exposure to HIV
      infection. The long-standing civil conflict in the Shan States of Burma is
      investigated as a contributing cause to the trafficking of ethnic Shan women and
      girls into the Southeast Asian sex industry, and to the subsequent high rates of
      HIV infection found among these women. The context of chronic human rights abuses
      in the Shan states is explored, as well as the effects of recent forced
      population transfers on the part of the Burmese Military Regime. Rights abuses
      specific to trafficked women may further increase their vulnerability to HIV and
      other STD. The need for a political resolution to the crisis in Burma is
      discussed, as are approaches aimed at preventing trafficking, empowering women
      already in the sex industry, and reducing the risks of HIV and other STD among
      these women and girls.

PMID- 11459404
TI  - Influence of buprenorphine analgesia on post-operative recovery in two strains of
      rats.
AB  - The objective of this study was to establish an effective post-operative
      analgesic regimen for Sprague-Dawley (SD) and Dark Agouti (DA) rats.
      Buprenorphine (0.01 or 0.05 mg/kg), a partial mu opioid agonist, was administered
      subcutaneously immediately on completion of a standardized surgical procedure,
      involving anaesthesia, laparotomy and visceral manipulation. Two of the four
      treatment groups and the saline control group received a second injection 9 h
      later. Behavioural observations by three independent observers provided no
      information in assessing pain in this model. All rats lost weight, consumed less
      food and water after surgery. On the first day, both SD and DA rats receiving
      buprenorphine lost less weight than untreated control groups. Using weight loss
      as an efficacy criterion, low-dose buprenorphine, given once or twice, provided
      effective analgesia in SD rats. A higher single dose provided no additional
      benefit and a second dose was detrimental, reducing body weight and food intake.
      In DA rats, the high dose, given twice, appeared to be more effective than the
      lower dose. All DA cage cohorts consumed < 10% pre-operative food despite
      buprenorphine treatment, suggesting a higher dosage may be necessary. However,
      all SD and 80% DA rats who received no buprenorphine gained body weight on the
      second day, whereas most of the buprenorphine-treated rats continued to lose
      weight for another 2 days, despite increased food consumption by both strains.
      Buprenorphine may adversely affect intestinal function over a number of days due
      to its enterohepatic circulation; this effect may be more severe in DA rats.
      Adverse metabolic effects of buprenorphine and other opioids may preclude their
      use in the future if it can be shown that non-steroidal anti-inflammatory drugs
      (NSAIDs) provide equally effective analgesia.

PMID- 11459405
TI  - Retrospective comparison of rat recovery weights using inhalation and injectable
      anaesthetics, nutritional and fluid supplementation for right unilateral
      neurosurgical lesioning.
AB  - Current veterinary standards of biomedical research support include refinements
      in animal models that are targeted at enhancing humane care and decreasing inter
      animal variability. This ultimately results in fewer numbers of animals being
      used and reduction in animal experimentation through mitigation of waste as well
      as faster research results. 6-hydroxydopamine-lesioning of the substantia nigra
      using a stereotactic frame device is a common procedure and is routinely
      performed under pentobarbital anaesthesia with monitoring by 8 h workforces. Our
      programme supports the humane care and use of several protocols involving the
      unilateral stereotactic-lesioning of rats for the purposes of creating research
      models of Parkinsonianism. Such procedures are commonly performed as unilateral
      in order to minimize aphagia and other untoward effects of the lesion. Generally,
      this procedure is considered minor because it involves a small incision, a
      cranial burrhole, and penetration of the dura. Inflammation and/or irritation of
      the ear canal can occur secondarily to the earbar placement procedure. Human
      patients undergoing similar procedures typically complain of headaches from loss
      of intracranial pressure; which is a transient outcome. Despite the perception of
      minor insult, we provided aggressive periprocedural care, and our veterinary
      staff documented weight loss that was often greater than 15% body weight during
      the first 3 days. The goal of this study was to evaluate refinements to improve
      this outcome. For humane concerns, and because of the need to begin experimental
      testing one week following surgery, a goal in the recent past has been to enhance
      outcome for researchers and animals by refining postoperative support modalities
      as well as by seeking the best anaesthetic regimen to shorten postoperative
      deviations from baseline. Analysis of three groups of rat patients lesioned by
      the same investigative group over the course of refinements made in our programme
      indicate that an early return of homeostasis was achieved by the use of
      inhalation anaesthetics as replacements for barbiturates in these models.
      Comparison with pentobarbital recipients also indicated that homeostasis is
      achieved earlier when barbiturates are utilized with fluid therapy and analgesics
      immediately after operative procedures rather than the next morning.

PMID- 11459406
TI  - Habituating pigs for in-pen, non-invasive biophysical skin analysis.
AB  - The purpose of this study was to develop a method for habituating pigs (Sus
      scrofa domestica, middle white strain) to enable non-invasive, biophysical
      measurements of dorsal skin to be obtained on a daily basis over a 7-week period,
      thus eliminating the need for anaesthesia or restraint. This was accomplished by
      associating measurements of transepidermal water loss (TEWL) and skin reflectance
      spectroscopy (SRS) with feeding times, and with positive reinforcement by
      allowing exercise outside the home pen. During the pig habituation period, a well
      defined series of behavioural changes were observed that included dominant/
      submissive leadership changes. Values of TEWL (6.29 +/- 1.25g.m(-2) x h(-1)) were
      in agreement with previous studies (7.56+/-2.90g.m 2 x h(-1)) obtained from
      unrestrained Yucatan hairless micro-pigs (Gabard et al. 1995). The coefficient of
      variance of TEWL and SRS measurements were comparable with those reported
      previously using anaesthetized pigs (Chilcott et al. 2000). These data imply that
      biophysical skin measurements obtained from unrestrained, conscious animals are
      comparable to those obtained from anaesthetized pigs and therefore, support the
      use of unrestrained pigs for non-invasive biophysical skin measurements.
      Habituating animals for in-pen, non-invasive, biophysical measurements has
      substantial implications for reducing and refining laboratory animal experiments
      in dermatological research without compromising animal welfare.

PMID- 11459407
TI  - Acclimatization and response of minipigs toward humans.
AB  - As a first step toward making an efficient acclimatization methodology for
      minipigs, the reaction of Gottingen minipigs, 3-24 months of age, toward humans
      was investigated. All minipigs were kept in an individual cage, and the reaction
      toward humans (acclimatization index) was evaluated by simple observations. The
      acclimatization index was evaluated as the total number of points scored (0-30
      points) based on the following criteria: (1) the position of the minipig when the
      cage door was opened; (2) the reaction of the minipig when the observer
      approached; and (31 the reaction of the minipig when the observer touched it.
      Subsequently, each animal was ranked by total points scored: 30 points = AA, 20
      points < or = A < 30 points, 10 points < or = B < 20 points, 0 points < or = C <
      10 points. Based on this evaluation, the reactions of minipigs under three
      conditions were investigated. The following findings were confirmed: first,
      minipig reaction to humans was influenced by monthly age; second, taming was
      possible under ordinary conditions of care, but we had to wait until 10 months of
      age on average for this to occur; third, if simple contact was made during care
      time, minipigs became tame within less than 4 weeks after the commencement of
      contact. We therefore consider it possible to artificially control the reaction
      of minipigs toward humans, and to make minipigs more available for experiments by
      adding control of the hereditary factors that influence this reaction.

PMID- 11459408
TI  - Long-term cannulation of the vena cava of rats for blood sampling: local and
      systemic effects observed by histopathology after six weeks of cannulation.
AB  - A cannulation system with fixation by a metal cuff around the tail was used for
      blood sampling. The cannula was guided subcutaneously and positioned in the vena
      cava after entering the body via the femoral vein. Histopathology was performed
      after long-term cannulation of up to 35 and 45 days. The presence of the cannula
      in the vena cava induced endothelial hypertrophy and hyperplasia accompanied by
      stromal hypertrophy. The endothelial activation was not limited to the vena cava
      but was also observed in both the cannulated vena iliaca and the contralateral
      control vena iliaca, the latter showing only minor alterations. In the lung,
      thrombi were noted in the larger lung arteries; and foreign body emboli, probably
      situated in the alveolar septi, could be detected occasionally. Inflammatory
      reactions in the tail at the site of cuff fixation consisted of a mixture of
      acute and chronic inflammatory responses. The chronic inflammation extended into
      the tail muscles, as shown by the presence of fibrous tissue associated with
      muscle degeneration. In conclusion, prolonged venous cannulation in rats resulted
      in local alterations in the veins, small emboli in the lungs and a moderate to
      marked inflammation in the tail. However, the procedure itself was well tolerated
      by the animals.

PMID- 11459409
TI  - A method of endoscopic endotracheal intubation in rabbits.
AB  - Endotracheal intubation in rabbits is a formidable task and has led to the
      devising of a new endoscopic method. Sixty New Zealand White rabbits (2.0-3.5 kg)
      underwent experimental left thoracotomy requiring mechanical ventilation. After
      anaesthetic induction was achieved, the animal was placed in a supine position. A
      rigid 30 degrees endoscope was passed through a 4.5 mm endotracheal tube (ET) and
      then used to advance, under direct vision, through the oropharynx and vocal
      cords. Once passing the vocal cords, the ET was advanced into the trachea as the
      endoscope was withdrawn. All animals were successfully intubated within 30 s to 2
      min and then ventilated. No complications or deaths occurred during or after
      intubation, or postoperatively. No instances of oesophageal intubation occurred.
      All animals survived long-term. Thirty animals underwent necropsy at 10 days and,
      30 at 30 days, with no postoperative evidence of orotracheal injury. We have
      established a new method of endotracheal intubation in rabbits. It is reliable,
      effective, non-traumatic, safe, and expeditious.

PMID- 11459410
TI  - Dimensions of rabbit subglottis and trachea.
AB  - One of the most challenging problems confronting otolaryngologists today remains
      the management of subglottic stenosis (SGS) in infants and children. It is a
      problem of decreased airway calibre, usually associated with prolonged
      intubation. The pathophysiology of an intubated airway becoming stenotic is not
      fully understood. Although an ideal animal model for studying SGS does not
      currently exist, several studies have used the rabbit's airway as a wound healing
      model. In order to establish such a model in the rabbit, sizes of the normal
      rabbit larynx must be measured in order to compare them to the diseased airway.
      Measuring the airway diameters of 35 rabbits ranging from 2.3-5.1 kg, the average
      airway at the level of the cricoid was found to be 5.81 mm (ventral-dorsal) by
      5.41 mm (lateral). These dimensions did not vary significantly with animal
      weight.

PMID- 11459411
TI  - Oral endotracheal intubation of rats for intratracheal instillation and aerosol
      drug delivery.
AB  - As reported in the literature, oral endotracheal intubation of rats is considered
      to be very difficult. Specialised equipment and complicated techniques have been
      described to perform this procedure. In our experiment we adopted a simple
      method, which allowed-without any complicated equipment-the insertion of a
      relatively wide tube into the trachea of rats, allowing drug administration.

PMID- 11459412
TI  - Development of a new aerosol delivery system for systemic pulmonary delivery in
      anaesthetized and orotracheal intubated rats.
AB  - Over the last decade, the systemic absorption of a broad range of therapeutics
      after pulmonary application has been demonstrated in animals as well as in
      humans. The most common method used in the laboratory is the intratracheal
      instillation of drugs in solution. This method is, however, unsatisfactory,
      because of discrepancies in particle distribution, clearance, kind of injury and
      bioavailability between instillation and inhalative application. On the other
      hand, a precise determination of the amount of drug applied by aerosol, and of
      the aerosol volume retained within the lungs is rather difficult, and is not
      possible for use with small animals such as mice or rats. We describe a system
      which allows the delivery of aerosols directly into the animal's lungs, and
      calculation of the amount of drug retained in the lungs. Our system was tested in
      vitro and in vivo and was shown to allow precise and efficient pharmacokinetic
      and toxicological studies to be carried out.

PMID- 11459413
TI  - A novel anaesthetic regimen for surgical procedures in guineapigs.
AB  - A combination of tiletamine/zolazepam, xylazine and butorphanol provides deep
      surgical, long-duration anaesthesia in guineapigs with a smooth induction and
      recovery period. The described dosages mainly affect the respiratory functions
      and blood gas parameters, with a minor-to-moderate effect on the cardiovascular
      system.

PMID- 11459414
TI  - A xylazine infusion regimen to provide analgesia in sheep.
AB  - The efficacy of continuous low-dose xylazine infusion following an initial
      loading dose in providing analgesia in sheep was examined using an algesimetry
      method based on a leg lifting response to an electrical stimulus. Sheep received
      a 5 mg intramuscular injection of xylazine followed by continuous infusion of
      intravenous xylazine (2mg/h) for 90 min. This treatment resulted in significant
      increases in the level of current required to elicit a leg lifting response (287%
      of baseline) and steady state analgesia was maintained from 10 min after the
      start of the infusion until the end of the experimental period. This protocol
      appears to be a simple and effective regimen for providing steady state analgesia
      in sheep.

PMID- 11459415
TI  - Investigation of excretion and absorption of different zinc salts in puppies.
AB  - The effects of dietary zinc on zinc absorption and excretion were evaluated with
      six 12-week-old beagles. The dogs were fed a commercial dry food later
      supplemented with 2 and 4mg/kg of body weight per day of either zinc sulphate,
      zinc acetate or zinc oxide. The concentrations of zinc in the urine and faeces of
      all treatment groups were increased depending on the type of zinc salts and the
      dosage in the diet (P < 0.05). The apparent absorption of zinc salts ranged from
      0.20 to 0.36. The zinc salt supplements at both dosages did not affect the
      digestibility of crude protein, fat and fibre. The zinc concentration in plasma
      varied with the type of zinc salt and with the dosage. The mean concentrations
      ranged from 61+/- 1.46 microg to 73 +/- 1.57 microg/dl in the unsupplemented
      groups, whereas it was 115 +/- 2.33 microg/dl in the group supplemented with zinc
      acetate at the highest dosage.

PMID- 11459416
TI  - Effect of herb supplement on hepatic enzyme activities in ddY mice.
AB  - Plasma glucose and lipid concentrations and hepatic enzyme activities were
      measured in male ddY mice supplemented with the herb, Echevaria glauca, to
      examine the effect of herbal treatment. In mice supplemented with the herb,
      plasma triglyceride (TG) and free fatty acid (FFA) concentrations decreased and
      hepatic glycolytic enzyme and glutathione peroxidase (GSHpx) activities increased
      significantly compared with those in the non-treated control mice. These
      increases in hepatic enzyme activities were not fully dose-dependent, however the
      higher dose and longer duration with herb supplement induced increases in the
      enzyme activities. It was found that dietary herb supplement caused an
      acceleration of hepatic function, judged by increased activities of glycolytic
      enzyme and GSHpx in ddY mice.

PMID- 11459417
TI  - Genetic structures and linguistic boundaries in Italy: a microregional approach.
AB  - The amount of genetic data (sequences, gene frequencies, and isonymy) available
      for the Province of Ferrara, Italy, makes this area one of the world's best
      known. In an effort to infer the underlying demographic processes, we studied the
      province's population structure by comparing geological, palaeoclimatic,
      archeological, historical, and linguistic data. This multilevel approach allowed
      us to date some characteristics of the population structure from prehistoric
      times to the Roman and Middle Ages, and to detect overlapping biological,
      cultural, and geographic boundaries. To detect linguistic boundaries within this
      area we turned pronunciation differences into phonetic notation. We then computed
      pairwise distances by using methods for multiple genetic sequence analysis, in
      order to obtain a distance matrix of the overall pronunciation variability. This
      approach enabled us to test the association among linguistic, geographical, and
      genetic distance matrices using the same statistical tests. Results indicate that
      demographic phenomena can be traced in an area as small as the Province of
      Ferrara and that, on a microregional scale, recent events may have influenced
      important aspects of the overall genetic variation.

PMID- 11459418
TI  - Genetic analyses in five western Mediterranean populations: variation at five
      tetrameric short tandem repeat loci.
AB  - A population study of the Balearic (Majorca, Minorca, Ibiza, Chueta) and Valencia
      populations was carried out using the short tandem repeat loci HUMTHO1, D4S243,
      HUMF13A1, D18S535, and D12S391. All the populations sampled were found to be in
      Hardy-Weinberg equilibrium for the five markers analyzed. Several statistical
      analyses showed a clear displacement of the Chueta and Ibiza populations from the
      other populations sampled. These results are in agreement with those obtained
      from the analysis of classical markers and mitochondrial DNA restriction fragment
      length polymorphisms, as well as with the history of these populations. A
      comparative study performed with other European populations using three of the
      five markers selected for this study (HUMTHO1, HUMF13A1, and D12S391) revealed a
      clear differentiation only of the Chueta population. We detected a tendency for a
      west-east clinal distribution in the frequency of the HUMTH01*6 allele in the
      European and Mediterranean area. This distribution could reflect some of the
      migratory events that have happened throughout that area's history. The forensic
      usefulness of these markers can be judged by their highly combined power of
      discrimination (0.999997).

PMID- 11459419
TI  - The peopling of New Guinea: evidence from class I human leukocyte antigen.
AB  - This study utilizes newly developed direct DNA typing methods for human leukocyte
      antigens (HLA) to provide new information about the peopling of New Guinea. The
      complete polymorphism of eight Melanesian populations was examined. The groups
      included were highlanders, northern and southern highlands fringe populations, a
      Sepik population, northern and southern coastal New Guinea populations, and
      populations from the Bismarck Archipelago and New Caledonia. The study concluded
      that, based on HLA and other evidence. Melanesians are likely to have evolved
      largely from the same ancestral stock as Aboriginal Australians but to have since
      differentiated. Highlanders are likely to be descendants of earlier migrations
      who have been isolated for a long period of time. Northern highlands fringe and
      Sepik populations are likely to share a closer common ancestry but to have
      differentiated due to long term isolation and the relative proximity to the coast
      of the Sepik. Southern fringe populations are likely to have a different origin,
      possibly from the Gulf region, although there may be some admixture with
      neighboring groups. Coastal populations have a wider range of polymorphisms
      because of the genetic trail left by later population movement along the coast
      from Asia that did not reach Australia or remote Oceania. Other polymorphisms
      found in these populations may have been introduced by the movement of
      Austronesian-speaking and other more recent groups of people into the Pacific,
      because they share many polymorphisms with contemporary southeast Asians,
      Polynesians, and Micronesians that are not found in highlanders or Aboriginal
      Australians. There is evidence suggestive of later migration to Melanesia from
      Polynesia and Micronesia.

PMID- 11459420
TI  - Reconstructing population history using JC virus: Amerinds, Spanish, and Africans
      in the ancestry of modern Puerto Ricans.
AB  - The roots of the Hispanic populations of the Caribbean Islands and Central and
      South America go back to three continents of the Old World. In Puerto Rico major
      genetic contributions have come from (1) Asians in the form of the aboriginal
      Taino population, an Arawak tribe, present when Columbus arrived on the Island,
      (2) Europeans, largely Spanish explorers, settlers, government administrators,
      and soldiers, and (3) Africans who came as part of the slave trade. Since JC
      virus (JCV) genotypes characteristic of Asia, Europe, and Africa have been
      identified, and excretion of JCV in urine has been proposed as a marker for human
      migrations, we sought to characterize the JCV strains present in a Caribbean
      Hispanic population. We found that the strains of JCV present today in Puerto
      Rico are those derived from the Old World populations represented there: Types 1B
      and 4 from Spain, Types 3A, 3B, and 6 from Africa, and Type 2A from Asia. The
      Type 2A genotype represents the indigenous Taino people. This JCV genotype was
      represented much more frequently (61%) than would be predicted by the trihybrid
      model of genetic admixture. This might be attributable to characteristics of JCV
      Type 2A itself, as well as to the nature of the early relationships between
      Spanish men and native women. These findings indicate that the JCV strains
      carried by the Taino Indians can be found in today's Puerto Rican population
      despite the apparent demise of these people more than two centuries ago.
      Therefore, molecular characterization of JCV provides a tool to supplement
      genetic techniques for reconstructing population histories including admixed
      populations.

PMID- 11459421
TI  - The 3120 +1G-->A splicing mutation in CFTR is common in Brazilian cystic fibrosis
      patients.
AB  - Cystic fibrosis patients from Rio de Janeiro, Brazil, were screened for mutations
      in exons 11 and 16 of the cystic fibrosis transmembrane conductance regulator
      gene (CFTR) by a nonradioactive single-stranded conformational polymorphism
      (SSCP) analysis technique. This procedure was used to evaluate the undefined
      mutations in one or both alleles of 64 cystic fibrosis patients. Unusual SSCP
      profiles were investigated further by sequence analysis. Two patients were shown
      to carry the G542X mutation (exon 11) and five had the splicing mutation 3120+1G-
      >A(intron 16), one of them being homozygous for the mutation. This is the first
      report of the 3120+ IG-->A mutation in Brazil. where it appears to be a frequent
      disease-associated molecular alteration in the CFTR gene.

PMID- 11459422
TI  - Effects of ascertainment bias on recovering human demographic history.
AB  - In recent years multilocus data sets have been used to study the demographic
      history of human populations. In this paper (1) analyses previously done on 60
      short tandem repeat (STR) loci are repeated on 30 restriction site polymorphism
      (RSP) markers; (2) relative population weights are estimated from the RSP data
      set and compared to previously published estimates from STR and craniometric data
      sets; and (3) computer simulations are performed to show the effects of
      ascertainment bias on relative population weight estimates. Not surprisingly,
      given that the RSP markers were originally identified in a small panel of
      Caucasians, estimates of relative population weights are biased and the European
      population weight is artificially inflated. However, the effects of ascertainment
      bias are not apparent in a principal components plot or estimates of FST.
      Ascertainment bias can have a large effect in other genetic systems with
      inherently low heterozygosity such as Alus or single nucleotide polymorphisms
      (SNPs), and care must be taken to have prior knowledge of how polymorphic markers
      in a given data set were originally identified. Otherwise, results can be skewed
      and interpretations faulty.

PMID- 11459423
TI  - Detection of novel ALAD gene polymorphisms using denaturing high-performance
      liquid chromatography.
AB  - Denaturing high-performance liquid chromatography (DH-PLC), which is based on the
      separation of mismatched DNA heteroduplexes, is one of the most promising
      techniques for detecting nucleotide polymorphisms. Lead is an important
      environmental toxicant that can impair the cardiovascular, central nervous,
      renal, reproductive, and hematologic systems. Here we compare the sensitivity and
      efficiency of DNA polymorphism detection in the delta-aminolevulinate dehydratase
      (ALAD) gene encoding the principal lead-binding protein in humans by means of
      DHPLC and direct DNA sequencing of polymerase chain reaction amplicons. In a
      sample of 48 unrelated Chinese women, five novel mutations were discovered in
      intron 6 (G13298C). exon 7 (C13348T), intron 8 (C13847T), intron 12 (C15096T),
      and the 3' untranslated region of exon 13 (A15762C). The allele frequencies of
      C13298, T13348, T13847, T15096, and C15762 alleles were 21.3%, 2.3%. 82.1%,
      62.5%, and 1.1%, respectively. All five mutations were detected by both DHPLC and
      direct DNA sequencing. No previously reported missense ALAD mutations were found
      in this Chinese population. Our study confirms that DHPLC provides an accurate
      method for the rapid identification of single nucleotide polymorphisms.

PMID- 11459424
TI  - Ethnic differences in distributions of GSTM1 and GSTT1 homozygous "null"
      genotypes in India.
AB  - We estimated the frequencies of GSTM1 and GSTT1 "null" homozygotes in 10
      different ethnic populations of India by a genotyping method based on polymerase
      chain reaction. These populations, inhabiting diverse geographical locations and
      occupying various positions in the sociocultural hierarchy, were represented by a
      sample of 299 unrelated individuals. Frequencies of GSTM1 and GSTT1 "null"
      homozygotes varied from 20% to 79% and 3% to 39%, respectively, across the study
      populations. Maximum frequencies of GSTM1 and GSTT1 "null" homozygotes (79% and
      39%, respectively) have been observed in the same population (Jamatia).
      Frequencies of homozygous "null" genotypes at the GSTM1 and GSTT1 loci show a
      significant positive correlation in these populations, which is contrary to
      expectations. A possible implication is that the two enzymes are working in
      tandem, instead of working in a complementary way.

PMID- 11459425
TI  - Further characterization of apolipoprotein B genetic variations in Taiwanese.
AB  - Apolipoprotein B (apoB, protein; APOB, gene) is the main protein component of low
      density lipoprotein (LDL) and plays an important role in blood lipid metabolism.
      Previously, we have reported four APOB coding regions, 5' signal peptide, and 3'
      repeat sequence polymorphisms in our population. In this report, we further
      characterize other APOB genetic variations. The results illustrate that the
      mutation frequencies for Arg3500Gln (1/846 alleles), Arg4019Trp (2/786 alleles), 
      265 C/T promoter region (0/264 alleles), and intron 2 A/G (0/450 alleles) are
      very low. Our population showed a frequency of 68.9% for the B4311 Ser allele.
      The B4311 Asn allele was associated with a higher apoB level than the Ser group
      (p < 0.05) in normal controls. In the normal controls, a higher B4311 Asn/Asn
      genotype frequency was found in the group with total cholesterol (TC) > 200 mg/dL
      and apoB concentration > 85 mg/dL than in the group with a TC < 200 mg/dL and
      apoB < 85 mg/dL (p = 0.03 for TC comparison).

PMID- 11459427
TI  - Population genetics of four PKLR intragenic polymorphisms in Portugal and Sao
      Tome e Principe (Gulf of Guinea).
AB  - Four intragenic PKLR polymorphisms [1705A/C, 1738C/T. T10/19, and (ATT)n
      microsatellite] were studied in normal population samples of Central Portugal and
      Sao Tome e Principe, a small archipelago located in the Gulf of Guinea, West
      Africa. For all loci, the observed genotype distributions do not deviate from
      Hardy-Weinberg equilibrium. The allele frequencies found in the Portuguese
      population are similar to those previously described in Caucasian populations.
      Mother-child pair analysis for the (ATT)n microsatellite does not show deviations
      to the Mendelian rules. In Sao Tome e Principe the biallelic polymorphisms
      1705A/C, 1738C/T, and T10/19 presented inverse allelic frequencies when compared
      with the Portuguese population. Two new alleles were found at the (ATT)n
      microsatellite. Significant statistical differences were found between both
      populations. The results showed that Sao Tomeans had higher haplotype diversity
      and lower linkage disequilibrium among the polymorphic sites. The PKLR intragenic
      polymorphisms, commonly used in haplotype analysis with the gene mutations in PK
      deficient patients, can thus be successfully employed in anthropological
      genetics.

PMID- 11459426
TI  - Skin reflectance in the Han Chinese and Tibetan populations.
AB  - Genetic and environmental factors are involved in the determination of skin
      pigmentation in humans. With the recent development of statistical and genetic
      tools in mapping complex traits in humans, it is becoming feasible to utilize
      such methods in identifying genes involved in skin pigmentation. Furthermore, the
      use of new portable reflectance spectroscopy instruments such as the Photovolt
      ColorWalk colorimeter allows researchers to measure skin reflectance of a large
      number of subjects with ease and accuracy. We used a new portable instrument
      (Photovolt ColorWalk) to study the skin reflectance of 372 Han Chinese and 274
      Tibetan individuals to establish background reflectance measurements of unexposed
      skin of the inner upper arm in these two populations. In addition, we explored
      the effect of various factors such as age and gender on skin reflectance.

PMID- 11459428
TI  - Glutamate release and neuronal damage in ischemia.
AB  - Neuronal injury caused by ischemia after occlusion of cerebral arteries is
      believed to be mediated by excessive activation of glutamate receptors. In the
      ischemic brain, extracellular glutamate is elevated rapidly after the onset of
      ischemia and declines following reperfusion. The mechanisms of the elevation of
      extracellular glutamate include enhanced efflux of glutamate and the reduction of
      glutamate uptake. The early efflux of glutamate occurring immediately after the
      onset of ischemia is mediated by a calcium-dependent process through activation
      of voltage-dependent calcium channels. The calcium-independent efflux at later
      stages is thought to be mediated primarily by glutamate transporters operating in
      the reverse mode owing to the imbalance of sodium ions across plasma membranes.
      Although high levels of glutamate in the extracellular space are well established
      to appear rapidly after the onset of ischemia, a direct linkage between the
      enhanced release of glutamate and the neuronal injury has not been fully
      established. In cultured neurons, ischemia induces efflux of glutamate into the
      extracellular space, but subsequent neuronal loss is not solely caused by the
      high glutamate concentration. In addition, cultured neurons can be rescued by
      NMDA antagonists added to the medium after exposure to glutamate receptor
      agonists. Two mechanisms can be proposed for neuroprotection by late NMDA
      receptor blockade, i.e., blocking of presynaptic release of glutamate after
      excessive activation of glutamate receptors, and blocking of postsynaptic
      sensitization of NMDA receptors.

PMID- 11459429
TI  - Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity
      and mRNA expression.
AB  - Studies initiated to characterise the catalytic activity and expression of CYP1A1
      in rat blood lymphocytes revealed significant activity of 7-ethoxyresorufin-O
      deethylase (EROD) in rat blood lymphocytes. Pretreatment with 3
      methylcholanthrene (MC) and beta-naphthoflavone (NF) resulted in significant
      induction in the activity of lymphocyte EROD suggesting that like the liver
      enzyme, EROD activity in lymphocytes is inducible and is mediated by the MC
      inducible isoenzymes of P450. The increase in the activity of EROD was associated
      with a significant increase in the apparent Vmax and affinity of the substrate
      towards EROD. That this increase in the activity of EROD could be primarily due
      to the increase in the expression of CYP1A1 isoenzymes was demonstrated by RT-PCR
      and western immunoblotting studies indicating an increase in the expression of
      CYP1A1 in blood lymphocytes after MC pretreatment. Significant inhibition in the
      EROD activity of MC induced lymphocyte by anti-CYP1A1/1A2 and alpha
      naphthoflavone further provided evidence that the CYP1A1/1A2 isoenzymes are
      involved in the activity of EROD in blood lymphocytes. The data indicating
      similarities in the regulation of CYP1A1 in blood lymphocytes with the liver
      isoenzyme suggests that factors which may affect expression of CYP1A1 in liver
      may also affect expression in blood lymphocytes and that blood lymphocytes could
      be used as a surrogates for studying hepatic expression of the xenobiotic
      metabolising enzymes.

PMID- 11459430
TI  - Increased prostacyclin synthesis by atherosclerotic arteries from estrogen
      treated monkeys.
AB  - We hypothesized that the atheroinhibitory and cardioprotective effects of
      estrogen may be mediated in part through increased prostacyclin formation by the
      artery wall. Atherosclerotic abdominal aorta was collected at necropsy from
      ovariectomized female monkeys fed an atherogenic diet alone or with added
      Premarin. Basal and arachidonate-stimulated prostacyclin and thromboxane
      synthesis by artery segments was measured by radioimmunoassay. In contrast to no
      observed differences in basal release of prostacyclin by the control and estrogen
      treated arteries, there was a marked increase (approximately 165%) in
      arachidonate-stimulated formation of prostacyclin by estrogen-treated arteries,
      and prostacyclin synthesis was inversely correlated with plaque size. No
      differences were observed in basal or arachidonate-stimulated thromboxane
      synthesis by the control and estrogen-treated arteries. In light of known
      antiatherogenic and vasodilatory effects of estrogen, increased prostacyclin
      synthesis by estrogen-treated arteries may, in part, explain estrogen's
      beneficial effects on the artery wall.

PMID- 11459431
TI  - 2,4,5-Trichlorophenoxyacetic acid inhibits apoptosis in PC12 cells.
AB  - 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) is an endocrine disrupter that exerts
      cytotoxic effects on organisms. In this study, the influence of 2,4,5-T at low
      concentrations on apoptosis in PC 12 cells was investigated. Although no
      apoptotic features were observed in PC12 cells treated with 2,4,5-T, it inhibited
      the DNA fragmentation induced by serum deprivation. In addition, the cell
      viability of PC12 cells increased after treatment with 2,4,5-T. In conclusion,
      2,4,5-T suppressed the apoptosis of the cultured cells. Since apoptosis is a
      morphological and biochemical description of a physiological mechanism of cell
      death that is commonly associated with programmed events necessary for
      development of individuals and organs, the inhibitory effect of 2,4,5-T on
      apoptosis might cause serious damage to cell homeostasis and differentiation.

PMID- 11459432
TI  - Hydromorphone-3-glucuronide: a more potent neuro-excitant than its structural
      analogue, morphine-3-glucuronide.
AB  - In humans, hydromorphone (HMOR) is metabolised principally by conjugation with
      glucuronic acid to form hydromorphone-3-glucuronide (H3G), a close structural
      analogue of morphine-3-glucuronide (M3G), the major metabolite of morphine. In a
      previous study we described the biochemical synthesis of H3G together with a
      preliminary evaluation of its pharmacology which revealed that it is a
      neuroexcitant in rats in a manner analogous to M3G. Thus the aims of the current
      study were to quantify the neuro-excitatory behaviours evoked by
      intracerebroventricular (icv) H3G in the rat and to define its potency relative
      to M3G. Groups of adult male Sprague-Dawley rats received icv injections (1
      microL) of H3G (1 - 3 microg), M3G (2 - 7 microg) or vehicle via a stainless
      steel guide cannula that had been implanted stereotaxically seven days prior to
      drug administration. Behavioural excitation was monitored by scoring fifteen
      different behaviours (myoclonic jerks, chewing, wet-dog-shakes, rearing, tonic
      clonic-convulsions, explosive motor behaviour, grooming, exploring, general
      activity, eating, staring, ataxia, righting reflex, body posture, touch evoked
      agitation) immediately prior to icv injection and at the following post-dosing
      times: 5, 15, 25, 35, 50, 65 and 80 min. H3G produced dose-dependent behavioural
      excitation in a manner analogous to that reported previously for M3G by our
      laboratory and reproduced herein. H3G was found to be approximately 2.5-fold more
      potent than M3G, such that the mean (+/- S.D.) ED50 values were 2.3 (+/- 0.1)
      microg and 6.1 (+/- 0.6) microg respectively. Thus, our data clearly imply that
      if H3G crosses the BBB with equivalent efficiency to M3G, then the myoclonus,
      allodynia and seizures observed in some patients dosed chronically with large
      systemic doses of HMOR, are almost certainly due to the accumulation of
      sufficient H3G in the central nervous system, to evoke behavioural excitation.

PMID- 11459433
TI  - Vascular adhesion molecule-1 and markers of platelet function before and after a
      treatment with iloprost or a supervised physical exercise program in patients
      with peripheral arterial disease.
AB  - Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were
      investigated in 24 patients with peripheral arterial disease at Fontaine stage II
      undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6
      h/day) or a 2 weeks supervised physical training, randomly assigned. Patients
      were studied before (T0) and after (T14) treatments and 10 days later (T24). The
      adhesion of washed platelets to fibrinogen coated microwells was reduced after
      treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM;
      p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to
      human plasma coated microwells was reduced only after treatment with iloprost
      (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor
      (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced
      after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical
      exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet
      thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients
      treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1);
      p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with
      iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both
      iloprost and physical exercise seem to act on reversible phenomena such as the
      expression of adhesion molecules or ex vivo adhesion, whereas only iloprost
      reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to
      be extended in time and to be associated with an improvement in vascular
      function.

PMID- 11459434
TI  - Inhibitor effect of omeprazole in isolated human myometrial smooth muscle.
AB  - The aim of the present study was to investigate the effect of omeprazole, an H+
      K+-ATPase inhibitor, in myometrial smooth muscle strips from women undergoing
      elective caesarean section at term. Isolated myometrial strips taken with
      informed consent were obtained from eight pregnant women undergoing elective
      caesarean section at term (not in labour) and mounted in organ baths for
      recording of isometric tension. We recorded the effect of increasing
      concentrations of omeprazole on spontaneous and Ca2+-induced contractions of
      myometrial smooth muscle and on contractions of myometrial smooth muscle
      pretreated with indomethacin (3 x 10(-6) M) and L-NAME (3 x 10(-5) M). Omeprazole
      (10(-4)-10(-3) M) decreased the amplitude and frequency of spontaneous
      contractions in a time- and concentration-dependent manner in all myometrial
      smooth muscle isolated from pregnant women. The decrease in amplitude of
      contractions in myometrial smooth muscle reached statistical significance
      beginning from the concentration of 3 x 10(-4) M. Addition of indomethacin (3 x
      10(-6) M) and L-NAME (3 x 10(-5) M) in to the organ baths 30 min before did not
      change relaxation responses to omeprazole. When 8 mM Ca2+-precontracted in Ca2+
      free medium myometrial smooth muscle were exposed to increasing concentrations of
      omeprazole (10(-5)-10(-3) M), omeprazole produced relaxation responses in a time-
      and concentration-dependent manner, reaching statistical significance at 10(-4)
      M. These results show: (1) omeprazole time- and concentration-dependently
      decreased spontaneous contractile activity in myometrial smooth muscle isolated
      from pregnant women, (2) omeprazole-induced relaxations was not influenced by
      indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME), suggesting that it
      is not mediated by cyclooxygenase products and nitric oxide, and (3) omeprazole
      brought about time- and concentration-dependently relaxation of myometrial smooth
      muscle precontracted by 8 mM Ca2+ in Ca2+-free medium. This effect of omeprazole
      may be due to blockade of the calcium channels.

PMID- 11459435
TI  - A comparison of chronic aspartame exposure to aspirin on inflammation,
      hyperalgesia and open field activity following carrageenan-induced monoarthritis.
AB  - The purpose of the present study was to investigate whether chronic aspartame
      exposure possesses analgesic and anti-inflammatory actions in the carrageenan
      induced monoarthritis model similar to those properties of aspirin. Prior
      research demonstrated that aspartame can reduce second phase formalin pain and
      increase motor activity in arthritic patients. Fifty-eight male Sprague-Dawly
      rats were treated with aspartame (25, 50, 100 mg/kg) or saline for six days. An
      additional group of animals received daily injections of saline and on the sixth
      treatment day, received a 150-mg/kg dose of aspirin 30-minutes prior to
      behavioral testing. On Day 6, animals received an intra-articular (i.a.)
      injection of 2% lambda carrageenan (CARR) or an equal volume of saline and were
      tested four hours later on threshold to mechanical and thermal stimuli, open
      field activity, and knee joint diameter. Aspirin-treated arthritic animals
      exhibited significantly less mechanical hyperalgesia and knee joint inflammation
      compared with vehicle treated arthritic animals. However, aspirin did not reverse
      thermal hyperalgesia or increase motor activity to control levels. Aspartame did
      not reduce inflammation, increase motor activity, or attenuate thermal allodynia,
      but at 50 mg/kg did attenuate mechanical allodynia compared with vehicle treated
      arthritic animals. The anti-hyperalgesic effect on mechanical hyperalgesia was
      not seen at 25 mg/kg or 100 mg/kg aspartame. These results suggest that a certain
      amount of aspartame may provide relief of arthritic pain to a similar degree as
      aspirin in some individuals. The specific effect of aspartame and aspirin on
      mechanical hyperalgesia should be considered when these agents are used for the
      therapeutic treatment of arthritic conditions.

PMID- 11459436
TI  - Nitric oxide dependent and independent effects of in vitro incubation or
      endotoxin on vascular reactivity in rat aorta.
AB  - We sought to delineate contributions of nitric oxide (NO) and other mechanisms to
      impairment of contraction and endothelium-dependent relaxation following
      prolonged in vitro incubation, endotoxin and interleukin-1 exposure in isolated
      rat aorta. Responses from freshly-dissected (control) rings +/-endothelium were
      compared with those from rings incubated in sterile, antibiotic containing medium
      +/- E. Coli endotoxin (LPS, 100 microg/ml) +/- interleukin-1 (IL-1, 40 ng/ml) at
      37 degrees C for 20-24 h. In some experiments, medium included dexamethasone
      (DEX, 1 microg/ml), cycloheximide (10 microg/ml), or N(G)-nitro-L-arginine (NNLA,
      10(-4)M). After incubation, medium nitrite was measured. Incubation alone,
      without addition of inflammatory mediators, impaired contraction in an agonist
      specific manner, by both NO-dependent and NO-independent mechanisms. Either LPS
      or IL-1 diminished contraction further, in a similarly heterogeneous manner. For
      example, contractions were changed in LPS-incubated endothelium-intact rings (vs.
      fresh controls) by -85%, +115%, -15%, -96%, and -37% for phenylephrine (PE),
      serotonin, prostaglandin F2alpha, angiotensin II, and U46619, respectively. NO
      synthase inhibition with NNLA either following, or during LPS incubation only
      partially normalized subsequent PE contractions, an effect which was smaller than
      that of DEX. Nitrite accumulation was inversely proportional to PE response, even
      though NO was not the sole mediator of LPS-impaired contraction. LPS and IL-1
      nearly abolished ACh-induced relaxation, which was only mildly impaired by
      incubation alone. We conclude that prolonged incubation impaired vasoconstriction
      via both NO synthase induction and NO-independent mechanisms. LPS or IL-1
      incubation impaired vasoconstriction further, primarily by NO-independent
      mechanisms. Moreover, vasoconstrictor responses following LPS varied with the
      agonist's ability to modulate endothelial NO release. These results are in accord
      with the failure of NO synthase inhibition to fully restore systemic vascular
      resistance indices in experimental endotoxemia or in hyperdynamic septic
      patients.

PMID- 11459437
TI  - The H3 receptor is involved in cholecystokinin inhibition of food intake in rats.
AB  - We investigated the peripheral effects of an H3-receptor agonist and an H3
      receptor antagonist (R)alpha-methylhistamine (Ralpha-MeHA) and thioperamide,
      respectively, on basal feeding and the CCK8-induced inhibition of food intake in
      rat. Intraperitoneal injection of thioperamide reduced food intake in a dose
      dependent manner with maximal inhibition (35%, P<0.01 vs saline) at 3 mg/kg.
      (R)alpha-MeHA (0.3-3 mg/kg i.p.), an H3-receptor agonist alone had no effect on
      feeding but reversed the thioperamide-induced inhibition of food intake in a dose
      dependent manner. The maximal feeding inhibitory dose of thioperamide (3 mg.kg
      i.p) increased by 40% and 22 % (P<0.01 vs saline) brain and stomach histamine
      contents, respectively. Histamine (0.3 - 6 mg/kg i.p.) and CCK-8 (3 - 30
      microg/kg i.p) also inhibited food intake in a dose-dependent manner. Inhibition
      was 20% to 40% for histamine and 40% to 80% (P<0.01 vs saline) for CCK8. CCK-8
      inhibition of feeding was increased by thioperamide and prevented by (R)alpha
      MeHA in a dose-dependent way. In addition, CCK-8 did not reduce food intake if
      rats were pretreated with pyrilamine or ranitidine postsynaptic H1- and H2
      receptor antagonists respectively. Our data suggest that the H3-receptor is
      involved in basal feeding. They also suggest that CCK satiety depends upon the
      release of histamine which acts on the H2- and H1-receptors, the final mediators
      of this effect.

PMID- 11459438
TI  - N-(3-(aminomethyl)benzyl)acetamidine, an inducible nitric oxide synthase
      inhibitor, decreases colonic inflammation induced by trinitrobenzene sulphonic
      acid in rats.
AB  - Gastrointestinal inflammation has been associated with an increased generation of
      nitric oxide (NO) and the expression of the inducible NO synthase (iNOS). Using
      an experimental model of colitis induced by trinitrobenzene sulphonic acid
      (TNBS), we sought to determine whether the administration of N-(3
      (Aminomethyl)benzyl)acetamidine (1400W), a specific inhibitor of iNOS, has a
      beneficial action on the colonic injury. 1400W (0.4 and 2 mg/kg/day) was
      administered intraperitoneally from day 5 to 10 after intrarectal instillation of
      TNBS. TNBS led to colonic ulceration and inflammation, an increase of colonic
      myeloperoxidase activity and the expression of the calcium-independent NOS from
      days 1 to 15. 1400W reduced the macroscopic damage and the histological changes
      induced by TNBS as well as the calcium-independent NOS activity and
      myeloperoxidase activity determined over 30 min after sacrifice. These findings
      indicate that the expression of iNOS accounts for most of the damage caused by
      TNBS and that the administration of 1400W after the onset of colitis has a
      beneficial action on the colonic injury.

PMID- 11459439
TI  - Biopharmaceutical statistics beyond 2000.

PMID- 11459440
TI  - Symmetry in square contingency tables: tests of hypotheses and confidence
      interval construction.
AB  - Bowker's test, a generalization of McNemar's test, performs well under the
      hypothesis of symmetry, but the estimator of variance used in the test is biased
      when the table is asymmetric and this calls into question the test's performance
      in non-null situations. We seek an alternative to Bowker's test in search of
      methods for simultaneous inference that are valid when the hypothesis of symmetry
      is false. We apply multivariate normal theory to develop chi-square tests and
      simultaneous confidence intervals for inferences concerning symmetry in k X k
      contingency tables. We propose a modified Wald statistic as a competitor to
      Bowker's test. We also proffer quadratic estimators of confidence intervals. In
      large samples, the recommended test statistic rejects the null hypothesis at the
      stated level of significance when the null hypothesis is true and always rejects
      with greater power than Bowker's test. The proffered interval estimators provide
      good simultaneous coverage of the pairwise differences between the population
      proportions at the stated confidence level.

PMID- 11459441
TI  - Carry-over effects in bioequivalence studies.
AB  - Carry-over effects are often considered to be one of the main problems of the
      cross-over design: should we adjust for carry-over or not? We attempt to answer
      this question by examining the observed frequency of carry-over effects in actual
      bioequivalence studies. A total of 96 six-sequence, three-period, three-treatment
      fed-fasted studies are analyzed for carry-over effects and 324 two-sequence, two
      period, two-treatment fasted studies are analyzed indirectly for carry-over
      effects via sequence effects. Two log-transformed pharmacokinetic variables, Cmax
      and AUC0-t, are modeled in an analysis of variance. The impact of statistically
      significant carry-over effects on bioequivalence results is examined and the
      rationale behind not adjusting for carry-over in bioequivalence studies is
      discussed.

PMID- 11459442
TI  - Confidence intervals and p-values for Williams' and other step-down multiple
      comparison tests against control.
AB  - When single-step multiple comparison tests against control, such as Dunnett's
      test, are used, p-values and confidence intervals can be reported. However,
      Williams' test and other step-down multiple comparison tests only provide results
      in terms of statistical significance. In this paper, approximate confidence
      intervals are proposed for some step-down multiple comparison tests and their
      coverage properties are assessed by simulation; p-values are readily calculated.
      The proposed simultaneous confidence intervals associated with Williams' test,
      Dunnett's step-down test, and the closed t test are all found to have good
      coverage, typically between 94% and 96% for a nominal value of 95%. Thus
      practicing statisticians can now quote p-values for these tests and use simple
      confidence intervals to aid interpretation of test results.

PMID- 11459443
TI  - Analyzing counts, durations, and recurrences in clinical trials.
AB  - In 1985 the (Byar and Blackard, Urology, Vol. X, 556-561, 1978) data set on
      bladder cancer became available to researchers. Since then, a number of studies
      have made use of it. However, none of these has fully utilized all of the data
      nor have they developed a methodology in which it is possible to estimate models
      of the number of recurrences and durations that are consistent with each other.
      The purpose of this research is to determine which, if any, of the two drugs used
      in the trial, pyridoxine and theotepa, were effective and, by example, illustrate
      procedures that could be useful in the analysis of other clinical trial data
      sets. First, the number of recurrences is modeled as a count using the Poisson
      and negative binomial distributions with covariates. Then Poisson models are
      tested on the durations. Finally, durations and tumor counts per recurrence are
      fitted to more general autoregressive Wiebull and negative binomial
      distributions, respectively. Poisson models for durations are rejected in favor
      of the more general autoregressive models. The data on durations and tumor counts
      are shown to be more reliable from an inference point of view than the data on
      the number of recurrences. The data on durations and tumor counts show quite
      conclusively that both drugs are effective in treating bladder cancer, a result
      that differs from what others have found.

PMID- 11459444
TI  - Comments on Nedelman and Jia's extension of Satterthwaite's approximation applied
      to pharmacokinetics.
AB  - In this letter, I have pointed out how the estimator given by Nedelman and Jia
      can be made unbiased with only a small modification. Moreover, I report on a new
      simulation study to show that the unbiased estimator of psi has favorable
      statistical properties in terms of confidence interval width and coverage
      probability. Further, the simulation study shows the effect of enforcement of the
      C-S inequality on the performance of both the biased and unbiased estimators.

PMID- 11459445
TI  - Simple way to estimate the median time and compare survival distributions in
      analgesic trials under informative censoring [letter].

PMID- 11459446
TI  - Accounting for dropout bias using mixed-effects models.
AB  - Treatment effects are often evaluated by comparing change over time in outcome
      measures. However, valid analyses of longitudinal data can be problematic when
      subjects discontinue (dropout) prior to completing the study. This study assessed
      the merits of likelihood-based repeated measures analyses (MMRM) compared with
      fixed-effects analysis of variance where missing values were imputed using the
      last observation carried forward approach (LOCF) in accounting for dropout bias.
      Comparisons were made in simulated data and in data from a randomized clinical
      trial. Subject dropout was introduced in the simulated data to generate ignorable
      and nonignorable missingness. Estimates of treatment group differences in mean
      change from baseline to endpoint from MMRM were, on average, markedly closer to
      the true value than estimates from LOCF in every scenario simulated. Standard
      errors and confidence intervals from MMRM accurately reflected the uncertainty of
      the estimates, whereas standard errors and confidence intervals from LOCF
      underestimated uncertainty.

PMID- 11459447
TI  - Synthesis of peptide-oligonucleotide conjugates for chromium coordination.
AB  - The synthesis of the first peptide-oligonucleotide conjugate designed to
      coordinate chromium(III) is reported. The overall goal of this work is to
      synthesize di-deoxynucleotides tethered with chromium(III)-coordinating
      appendages to model chromium-DNA-protein cross-links, which are a type of DNA
      lesion that may be involved in chromium-induced cancers. The conjugate
      dGp(NHCH(2)CH(2)S-Ac-Gly-Ser-Gly-OH)G was made by coupling the peptide, ClAc-Gly
      Ser-Gly-OH, and dinucleotide, dGp(NHCH(2)CH(2)SH)G, through a thioether moiety.
      The conjugate was characterized by HPLC and mass spectrometry. Previously
      reported methods for small-scale solid-phase synthesis of peptides and
      dinucleotide were unsuitable; therefore, gram-scale solution-phase methods were
      developed. We also report the gram-scale syntheses of two other serine-containing
      peptides, ClAc-betaAla-Ser-Gly-OH and ClAc-Ser-Gly-OH, and three histidine
      containing peptides, ClAc-Gly-His-Gly-OH, ClAc-betaAla-His-Gly-OH, and ClAc-His
      Gly-OH. The synthesis and characterization of chromium-containing peptide
      oligonucleotide conjugates will ultimately help us to understand chromium-DNA
      interactions at a molecular level, which is necessary before we can determine how
      chromium causes cancer.

PMID- 11459448
TI  - Syntheses of Curcumin Bioconjugates and Study of Their Antibacterial Activities
      against beta-Lactamase-Producing Microorganisms.
AB  - In the present study curcumin bioconjugates, viz. di-O-glycinoylcurcumin (I), di
      O-glycinoyl-C(4)-glycylcurcumin (II), 5'-deoxy-5'-curcuminylthymidine (5'-cur-T)
      (IV), and 2'-deoxy-2'-curcuminyluridine (2'-cur-U) (V) have been synthesized and
      characterized by elemental analysis and (1)H NMR. The turmeric peptide (Tp) was
      isolated from the aqueous turmeric extract of the turmeric rhizome. The
      antibacterial activity of these four bioconjugates and also of the turmeric
      peptide and sodium salt of curcumin (III) have been tested particularly for beta
      lactamase-producing microorganisms.

PMID- 11459449
TI  - Studies on protein-liposome coupling using novel thiol-reactive coupling lipids:
      influence of spacer length and polarity.
AB  - To optimize the preparation of immunoliposomes, we investigated the coupling of
      thiolated IgG and BSA to liposomes using a novel group of coupling lipids. All
      lipids consist of cholesterol as membrane anchor and a thiol-reactive maleimide
      headgroup, linked by a spacer that differs in length and polarity (ethylene
      glycol, tetraethylene glycol, PEG 400, PEG 1000, dodecyl). In addition, lipids
      differ in the electrophilicity of the maleimide group (p- or m-maleimidobenzoic
      ester). In the case of BSA, coupling efficiency strongly depended on the
      electrophilicity of the maleimide group as well as on the spacer polarity: The
      less electrophilic meta constitution seems to be an advantage over the p
      maleimidobenzoic ester, resulting in higher coupling efficiency. Polar spacers
      (tetraethylene glycol, 46%) achieved a higher coupling efficiency than a nonpolar
      spacer with approximately the same length (dodecyl, 15%).When liposomes
      containing coupling lipids with the spacers tetraethylene glycol, PEG 400, and
      PEG 1000 were linked to BSA, coupling efficiencies were in a medium range and
      similar (41-46%) but were lower for the short ethylene glycol spacer (30%). In
      contrast, for IgG coupling efficiencies correlated with increasing spacer length.
      Best results were obtained using coupling lipids with a long polar spacer (PEG
      1000) (65%), whereas a coupling lipid bearing a short spacer (ethylene glycol)
      resulted in a low coupling efficiency of 12%.

PMID- 11459450
TI  - Enhancement of gene expression by polyamidoamine dendrimer conjugates with alpha
      , beta-, and gamma-cyclodextrins.
AB  - To improve the transfection efficiency of nonviral vector, we synthesized the
      starburst polyamidoamine dendrimer conjugates with alpha-, beta-, and gamma
      cyclodextrins (CDE conjugates), expecting the synergistic effect of dendrimer and
      cyclodextrins (CyDs). The (1)H NMR spectroscopic data indicated that alpha-, beta
      , and gamma-CyDs are covalently bound to dendrimer in a molar ratio of 1:1. The
      agarose gel electrophoretic studies revealed that CDE conjugates formed the
      complexes with plasmid DNA (pDNA) and protected the degradation of pDNA by DNase
      I in the same manner as dendrimer. CDE conjugates showed a potent luciferase gene
      expression, especially in the dendrimer conjugate with alpha-CyD (alpha-CDE
      conjugate) which provided the greatest transfection activity (approximately 100
      times higher than those of dendrimer alone and of the physical mixture of
      dendrimer and alpha-CyD) in NIH3T3 and RAW264.7 cells. In addition, the gene
      transfer activity of alpha-CDE conjugate was superior to that of Lipofectin. The
      enhancing gene transfer effect of alpha-CDE conjugate may be attributable to not
      only increasing the cellular association, but also changing the intracellular
      trafficking of pDNA. These findings suggest that alpha-CDE conjugate could be a
      new preferable nonviral vector of pDNA.

PMID- 11459451
TI  - Significance of substrate hydrophobicity for recognition by an oligopeptide
      transporter (PEPT1).
AB  - Our previous paper [(1999) Bioconjugate Chem. 10, 24-31] pointed out that
      hydrophobicity of substrates/inhibitors plays an important role in the
      recognition by an oligopeptide transporter (PEPT1) expressed in the human
      intestinal epithelial cell line Caco-2. To determine the significance of that
      hydrophobicity, we have now synthesized dipeptide analogues conjugating the
      epsilon-amino group of Lys in Val-Lys with aliphatic carboxylic acids: acetic
      acid (C2), propanoic acid (C3), pentanoic acid (C5), hexanoic acid (C6), and
      decanoic acid (C10). The affinities of these conjugates were estimated by their
      inhibition of the accumulation rate of Gly-Sar, a well-established substrate for
      PEPT1. With the increase in length of the hydrocarbon chain of the conjugates,
      i.e., in the hydrophobicity of the conjugates, the inhibition strengthened. Dixon
      Webb plot analysis of the inhibition by the C10-conjugated dipeptide showed
      competitive inhibition. The trans-stimulation effect of Val-Lys conjugated to C10
      or C5 on the uptake of Ceftibuten was observed using rat brush border membrane
      vesicles. This findings showed that these conjugates are transportable
      substrates. These results confirmed that the hydrophobicity of
      substrates/inhibitor is one of the factors in the recognition by PEPT1.

PMID- 11459452
TI  - Energy-transfer cassette labeling for capillary array electrophoresis short
      tandem repeat DNA fragment sizing.
AB  - Energy-transfer (ET) dye-labeled primers significantly improve fluorescent DNA
      detection because they permit excitation at a single common wavelength and they
      produce well separated and intense acceptor dye emission. Recently, a new ET
      cassette technology was developed [Berti, L. et al. (2001) Anal. Biochem. 292,
      188-197] that can be used to label any PCR, sequencing, or other primer of
      interest. In this report we examine the utility of this ET cassette technology by
      labeling seven different short tandem repeat (STR) specific primers with each of
      the four ET cassettes and analyzing the PCR products generated on a MegaBACE-1000
      capillary array electrophoresis system. More than 60 amplicons were generated and
      successfully analyzed with the ET cassette-labeled primers. Both forward and
      reverse primers were labeled for multiplex PCR amplification and analysis. Single
      base pair resolution was achieved with all four ET cassettes. This ET cassette
      primer labeling procedure is ideally suited for creating four-color fluorescent
      ET primers for STR and other DNA assays where large numbers of different loci are
      analyzed including sequencing, genetic identification, gene mapping, loss of
      heterozygosity testing, and linkage analysis.

PMID- 11459453
TI  - Triple helix-forming oligonucleotides conjugated to indolocarbazole poisons
      direct topoisomerase I-mediated DNA cleavage to a specific site.
AB  - Topoisomerase I is an ubiquitous DNA-cleaving enzyme and an important therapeutic
      target in cancer chemotherapy for camptothecins as well as for indolocarbazole
      antibiotics such as rebeccamycin. To achieve a sequence-specific cleavage of DNA
      by topoisomerase I, a triple helix-forming oligonucleotide was covalently linked
      to indolocarbazole-type topoisomerase I poisons. The three indolocarbazole
      oligonucleotide conjugates investigated were able to direct topoisomerase I
      cleavage at a specific site based upon sequence recognition by triplex formation.
      The efficacy of topoisomerase I-mediated DNA cleavage depends markedly on the
      intrinsic potency of the drug. We show that DNA cleavage depends also upon the
      length of the linker arm between the triplex-forming oligonucleotide and the
      drug. Based on a known structure of the DNA-topoisomerase I complex, a molecular
      model of the oligonucleotide conjugates bound to the DNA-topoisomerase I complex
      was elaborated to facilitate the design of a potent topoisomerase I inhibitor
      oligonucleotide conjugate with an optimized linker between the two moieties. The
      resulting oligonucleotide-indolocarbazole conjugate at 10 nM induced cleavage at
      the triple helix site 2-fold more efficiently than 5 microM of free
      indolocarbazole, while the other drug-sensitive sites were not cleaved. The
      rational design of drug-oligonucleotide conjugates carrying a DNA topoisomerase
      poison may be exploited to improve the efficacy and selectivity of
      chemotherapeutic cancer treatments by targeting specific genes and reducing drug
      toxicity.

PMID- 11459454
TI  - Paramagnetic water-soluble metallofullerenes having the highest relaxivity for
      MRI contrast agents.
AB  - Water-soluble gadolinium (Gd) endohedral metallofullerenes have been synthesized
      as polyhydroxyl forms (Gd@C(82)(OH)(n)(), Gd-fullerenols) and their paramagnetic
      properties were evaluated by in vivo as well as in vitro for the novel magnetic
      resonance imaging (MRI) contrast agents for next generation. The in vitro water
      proton relaxivity, R(1) (the effect on 1/T(1)), of Gd-fullerenols is
      significantly higher (20-folds) than that of the commercial MRI contrast agent,
      Magnevist (gadolinium-diethylenetriaminepentaacetic acid, Gd-DTPA) at 1.0 T close
      to the common field of clinical MRI. This unusually high proton relaxivity of Gd
      fullerenols leads to the highest signal enhancement at extremely lower Gd
      concentration in MRI studies. The strong signal was confirmed in vivo MRI at
      lung, liver, spleen, and kidney of CDF1 mice after i.v. administration of Gd
      fullerenols at a dose of 5 micromol Gd/kg, which was 1/20 of the typical clinical
      dose (100 micromol Gd/kg) of Gd-DTPA.

PMID- 11459455
TI  - Immunological properties of uricase conjugated to neutral soluble polymers.
AB  - For a comparative study of immunological properties of protein-polymer
      conjugates, uricase was modified with (a) poly(N-vinylpyrrolidone) 6000 Da, (b)
      poly(N-acriloylmorpholine) 6000 Da, (c) branched monomethoxypoly(ethylene glycol)
      10000 Da, and (d) linear monomethoxypoly(ethylene glycol) 5000 Da. Spectroscopic
      studies performed by UV, fluorescence, and circular dichroism did not show any
      relevant difference in protein conformation among the native and the conjugates.
      Immunological studies showed that both uricase antigenicity and immunogenicity
      were altered by polymer conjugation to an extent that depended upon the polymer
      composition; in particular, monomethoxypoly(ethylene glycol) 10000 Da remarkably
      reduced the protein antigenicity, while unexpectedly, the poly(N
      vinylpyrrolidone) derivative presented higher antigenicity than the native
      protein. In Balb/c mice, the native protein elicited a rapid and intense
      immunoresponse whereas all the conjugates induced a lower production of anti
      native uricase antibodies. The rank order of immunogenicity was native uricase >
      uricase-poly(N-vinylpyrrolidone) > or = uricase-poly(N-acriloylmorpholine) >
      uricase-monomethoxypoly(ethylene glycol) 5000 Da > uricase
      monomethoxypoly(ethylene glycol) 10000 Da. The four conjugates also induced anti
      polymer immunoresponse. Anti poly(N-vinylpyrrolidone) and anti poly(N
      acriloylmorpholine) antibodies were generated from the first immunization while
      low levels of anti polymer antibodies were found with both poly(ethylene glycol)
      conjugates only after the second immunization.

PMID- 11459456
TI  - New TFO conjugates containing a carminomycinone-derived chromophore.
AB  - Conjugates obtained by linking the anthracycline intercalating chromophore to
      triple helix forming oligonucleotides (TFOs) have been used in a physicochemical
      study of the stability of triple helices with DNA sequences of pharmacological
      relevance. The intercalating moiety is represented by carminomycinone derivatives
      obtained upon O-demethylation and hydrolysis of the glycosidic linkage of
      daunomycin followed by the introduction of an alkylating residue at two different
      positions. Results of experiments with a polypurinic region present in the
      multidrug resistance (MDR) gene indicate that the stability of the triple helix
      is significantly enhanced by replacement of C's with (5-Me)C's in the TFO
      sequences tested. The stability is not changed when a 3'-TpT is present in place
      of a 3'-CpG at the presumed intercalation site of the anthraquinone chromophore.
      The same carminomycinone derivatives were used for the preparation of conjugates
      able to form triple helices with the polypurine tract (PPT) present in the human
      integrated genome of HIV-1 infected cells. Three different TFOs
      (T(4)(Me)CT(4)(Me)CC, C2; T(4)(Me)CT(4)(Me)CC(Me)CC(Me)CCT, C6; and
      T(4)(Me)CT(4)G(6), G6) were designed and linked to the anthraquinone moiety.
      These conjugates showed a significantly enhanced ability to bind the PPT region
      of HIV with respect to the nonconjugated TFOs.

PMID- 11459457
TI  - Different strategies for formation of pegylated EGF-conjugated PEI/DNA complexes
      for targeted gene delivery.
AB  - With the aim of generating gene delivery systems for tumor targeting, we have
      synthesized a conjugate consisting of polyethylenimine (PEI) covalently modified
      with epidermal growth factor (EGF) peptides. Transfection efficiency of the
      conjugate was evaluated and compared to native PEI in three tumor cell lines: KB
      epidermoid carcinoma cells, CMT-93 rectum carcinoma cells, and Renca-EGFR renal
      carcinoma cells. Depending on the tumor cell line, incorporation of EGF resulted
      in an up to 300-fold increased transfection efficiency. This ligand-mediated
      enhancement and competition with free EGF strongly suggested uptake of the
      complexes through the EGF receptor-mediated endocytosis pathway. Shielded
      particles being crucial for systemic gene delivery, we studied the effect of
      covalent surface modification of EGF-PEI/DNA complexes with a poly(ethylene
      glycol) (PEG) derivative. An alternative way for the formation of PEGylated EGF
      containing complexes was also evaluated where EGF was projected away from PEI/DNA
      core complexes through a PEG linker. Both strategies led to shielded particles
      still able to efficiently transfect tumor cells in a receptor-dependent fashion.
      These PEGylated EGF-containing complexes were 10- to 100-fold more efficient than
      PEGylated complexes without EGF.

PMID- 11459458
TI  - Mixed-ligand technetium(III) complexes with tetradendate/monodendate
      NS(3)/isocyanide coordination: a new nonpolar technetium chelate system for the
      design of neutral and lipophilic complexes stable in vivo.
AB  - Starting from the tripodal ligand 2,2',2' '-nitrilotris(ethanethiol) (NS(3)) and
      isocyanides (CNR) as co-ligands, neutral mixed-ligand technetium(III) complexes
      of the general formulation [Tc(NS(3))(CNR)] have been synthesized and
      characterized. The (99)Tc complexes can be( )()obtained by a two-step
      reduction/substitution procedure starting from [TcO(4)](-) via the phosphine
      containing precursor complex [Tc(NS(3))(PMe(2)Ph)]. As shown by X-ray structural
      analyses, the complexes adopt a nearly ideal trigonal-bipyramidal geometry with
      the trigonal plane formed by the three thiolate sulfurs of the tripodal ligand.
      The central nitrogen atom of the chelate ligand and the monodendate isocyanides
      occupy the apical positions. The no-carrier-added preparation of the
      corresponding (99m)Tc complexes was performed by a one-step procedure starting
      from (99m)[TcO(4)](-) with stannous chloride as reducing agent. Biodistribution
      studies in the rat demonstrated for the nonpolar, lipophilic compounds a
      significant initial brain uptake. In vitro challenge experiments with glutathione
      clearly indicated that no transchelation reaction occurs. Furthermore, there were
      no indications for reoxidation of Tc(III) to Tc(V) species or pertechnetate. We
      propose this type of complexes as a useful tool in the design of lipophilic
      (99m)Tc or (186)Re/(188)Re radiopharmaceuticals.

PMID- 11459459
TI  - Poly(ethylene glycol)-conjugated anti-EGF receptor antibody C225 with radiometal
      chelator attached to the termini of polymer chains.
AB  - Several biological barriers, including significant liver uptake, limit the
      clinical application of radiolabeled antibodies in radioimmunoscintigraphy. Here,
      a general approach is described for radiolabeling of monoclonal antibodies
      conjugated with poly(ethylene glycol) (PEG). This strategy is demonstrated with
      C225, a monoclonal antibody directed against epidermal growth factor (EGF)
      receptor. We synthesized a heterofunctional PEG with one end attached to a
      radiometal chelator, diethylenetriaminepentaacetic acid (DTPA), and the other end
      to a protected thiol group, S-acetylthioacetate. After a deprotection step, the
      resulting DTPA-PEG-SH was conjugated to maleimide-activated C225 to yield DTPA
      PEG-C225 conjugate. Characterization of DTPA-PEG-C225 with immunoprecipitation
      and Western blot analysis revealed that the conjugate was biologically active in
      binding to the EGF receptor in A431 cells. Competitive EGF receptor binding assay
      in MDA-MB-468 cells showed that DTPA-PEG-C225, with up to 60% of the amino groups
      in C225 substituted, retained 66% of C225's binding affinity. Moreover, DTPA-PEG
      C225 with increasing degrees of NH(2) substitution from 20% to 70% retained the
      activity of C225 to induce apoptosis in DiFi cells. More importantly, DTPA-PEG
      C225 demonstrated less nonspecific interaction than DTPA-C225. Pharmacokinetic
      analysis using (111)In-labeled compounds revealed narrower steady-state
      distribution of (111)In-DTPA-PEG-C225 than (111)In-DTPA-C225, probably due to
      reduced nonspecific binding of PEG-modified antibody to tissues. The terminal
      half-life (t(1/2,)(gamma)) of (111)In-DTPA-PEG-C225, 21.1 h, was shorter than
      that of (111)In-DTPA-C225, 52.9 h. These data suggest that (111)In-DTPA-PEG-C225
      may provide better imaging characteristics than (111)In-DTPA-C225, and that using
      PEG as a linker between the monoclonal antibody and DTPA may be a promising
      strategy in optimizing the imaging characteristics of immunoscintigraphic agents.

PMID- 11459460
TI  - Stabilization of (90)y-labeled DOTA-biomolecule conjugates using gentisic acid
      and ascorbic acid.
AB  - Radiolytic degradation of radiolabeled compounds is a major challenge for the
      development of new therapeutic radiopharmaceuticals. The goal of this study is to
      explore the factors influencing the solution stability of a (90)Y-labeled DOTA
      peptide conjugate (RP697), including the amount of total activity, the activity
      concentration, the stabilizer concentration, and the storage temperature. In
      general, the rate of radiolytic decomposition of RP697 is much slower at the
      lower activity concentration (<4 mCi/mL) than that at the higher concentration
      (>10 mCi/mL). RP697 remains relatively stable at the 20 mCi level and room
      temperature while it decomposes rapidly at the 100 mCi level under the same
      storage conditions. Radical scavengers, such as gentisic acid (GA) and ascorbic
      acid (AA), were used in combination with the low temperature (-78 degrees C) to
      prevent the radiolytic decomposition of RP697. It was found that RP697 remains
      stable for at least 2 half-lives of (90)Y when GA or AA (10 mg for 20 mCi of
      (90)Y) is used as a stabilizer when the radiopharmaceutical composition is stored
      at -78 degrees C. The stabilizer (GA and AA) can be added into the formulation
      either before or after radiolabeling. The post-labeling approach is particularly
      useful when the use of a large amount of the stabilizer interferes with the
      radiolabeling. The radiopharmaceutical composition developed in this study can
      also apply to other (90)Y-labeled DOTA-biomolecule conjugates. The amount of the
      stabilizer used in the radiopharmaceutical composition and storage temperature
      should be adjusted according to the sensitivity of the radiolabeled DOTA
      biomolecule conjugate toward radiolytic decomposition.

PMID- 11459461
TI  - (90)Y and (177)Lu labeling of a DOTA-conjugated vitronectin receptor antagonist
      useful for tumor therapy.
AB  - The (90)Y and (177)Lu complexes (RP697 and RP688, respectively) of a DOTA
      conjugated vitronectin receptor antagonist (SU015: 2-(1,4,7,10-tetraaza-4,7,10
      tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu(cyclo[Lys-Arg-Gly-Asp-D-Phe])
      cyclo[Lys-Arg-Gly-Asp-D-Phe]) were prepared by reacting SU015 with the radiometal
      chloride in ammonium acetate buffer (pH > 7.2) in the presence of an antioxidant
      (sodium gentisate, GA). Through a series of radiolabeling experiments, it was
      found that there are many factors influencing the rate of (90)Y chelation and the
      radiolabeling efficiency of SU015. These include the purity of SU015, the pH,
      reaction temperature, and heating time, as well as the presence of trace metal
      contaminants, such as Ca(2+), Fe(3+), and Zn(2+). The chelation of (90)Y by SU015
      is slow, so that heating at elevated temperatures (50-100 degrees C) is needed to
      complete the (90)Y-labeling. The rate of (90)Y chelation is also dependent on the
      pH of the reaction mixture. Under optimized radiolabeling conditions (pH 7.2-7.8
      and heating at 50-100 degrees C for 5-10 min), the minimum amount of SU015
      required to achieve 95% RCP for RP697 is approximately 25 microg for 20 mCi of
      (90)YCl(3) corresponding to a SU015:(90)Y ratio of approximately 30:1.

PMID- 11459462
TI  - In vitro gene transfer with a novel galactosylated spermine bolaamphiphile.
AB  - We describe the synthesis of a alpha-galacto-omega-spermine bolaamphiphile
      (GalSper) and report on the gene transfer mediated with lipoplexes it forms
      either when used alone or in conjunction with DOPE or with DOGS (Transfectam).
      Lipofection with GalSper was investigated with human HepG2 or murine BNL-CL2
      hepatocytes expressing the asialo-glycoprotein (ASGP) receptor, which displays a
      high affinity for galactosyl residues, or with A549 cells which do not express
      ASGP. Although lower luciferase expression levels in BNL-CL2 and in HepG2 cells
      were obtained with GalSper/DOPE N/P 2.5 lipoplexes as compared with control
      DOGS/DOPE N/P 2.5 particles or with the more positively charged N/P 5 particles
      (yet through a different mechanism), specific receptor-mediated endocytosis of
      DNA can be achieved with this targeted cationic GalSper bolaamphiphile presenting
      a single galactose residue. The present work suggests that GalSper-based DNA
      formulations appear as promising synthetic vectors for specific gene delivery to
      ASGP(+) cells.

PMID- 11459463
TI  - A convenient solid-phase method for synthesis of 3'-conjugates of
      oligonucleotides.
AB  - We present a new procedure for the preparation of 3'-conjugates of
      oligonucleotides through solid-phase synthesis. A suitable universal solid
      support was readily prepared using a series of peptide-like coupling reactions to
      incorporate first a spacer and then an L-homoserine branching unit. The N-alpha
      position of the homoserine carries an Fmoc protecting group that is removed by
      treatment with piperidine to liberate an amino group suitable for attachment of
      the conjugate (e.g., small organic molecule, fluorescent group, cholesterol,
      biotin, amino acid, etc.) or for assembly of a short peptide. The side-chain
      hydroxyl group of the homoserine carries a trityl protecting group. After TFA
      deprotection, the hydroxyl group acts as the site for oligonucleotide assembly.
      An additional spacer, such as aminohexanoyl, may be incorporated easily between
      the conjugate molecule and the oligonucleotide. A number of examples of synthesis
      of 3'-conjugates of oligonucleotides and their analogues are described that
      involve standard automated oligonucleotide assembly and use of commercially
      available materials. The linkage between oligonucleotide and 3'-conjugate is
      chirally pure and is stable to conventional ammonia treatment used for
      oligonucleotide deprotection and release from the solid support. The homoserine
      functionalized solid support system represents a simple and universal route to 3'
      conjugates of oligonucleotides and their derivatives.

PMID- 11459464
TI  - Avidin-dendrimer-(1B4M-Gd)(254): a tumor-targeting therapeutic agent for
      gadolinium neutron capture therapy of intraperitoneal disseminated tumor which
      can be monitored by MRI.
AB  - Peritoneal carcinomatosis is a late stage in cancer progress, for which no
      effective therapeutic modality exists. Targeting therapeutic agents to
      disseminated lesions may be a promising modality for treating peritoneal
      carcinomatosis. Gadolinium ((157,155)Gd) is known to generate Auger and internal
      conversion electrons efficiently by irradiation with a neutron beam. Auger
      electrons from neutron-activated Gd(III) are strongly cytotoxic, but only when
      Gd(III) atoms have been internalized into the cells. In the present
      investigation, we have developed a quickly internalizing tumor-targeting system
      to deliver large quantities of Gd(III) atoms into tumor cells to generate the
      Auger emission with an external neutron beam. Simultaneously, one would be able
      to image its biodistribution by MRI with a shortened T1 relaxation time. Avidin
      G6-(1B4M-Gd)(254) (Av-G6Gd) was synthesized from generation-6 polyamidoamine
      dendrimer, biotin, avidin, and 2-(p-isothiocyanatobenzyl)-6-methyl
      diethylenetriaminepentaacetic acid (1B4M). The Av-G6Gd was radiolabeled with
      Gd(III) doped with (153)Gd. All of the 1B4M's on the conjugate were fully
      saturated with Gd(III) atoms. An in vitro internalization study showed that Av
      G6Gd accumulated and was internalized into SHIN3 cells (a human ovarian cancer)
      50- and 3.5-fold greater than Gd-DTPA (Magnevist) and G6-(1B4M-Gd)(256) (G6Gd).
      In addition, accumulation of Gd(III) in the cells was detected by the increased
      signal on T1-weighted MRI. A biodistribution study was performed in nude mice
      bearing intraperitoneally disseminated SHIN3 tumors. Av-G6Gd showed specific
      accumulation in the SHIN3 tumor (103% ID/g) 366- and 3.4-fold greater than Gd
      DTPA (0.28% ID/g, p < 0.001) and G6Gd (30% ID/g, p < 0.001) 1 day after i.p.
      injection. Seventy-eight percent of the tumor-related radioactivity of Av-G6Gd in
      the SHIN3 tumor was located inside the cells. The SHIN3 tumor-to-normal tissue
      ratio was greater than 17:1 in all organs and increased up to 638:1 at 1 day
      after i.p. injection. In conclusion, a sufficient amount (162 ppm) of Av-G6Gd was
      accumulated and internalized into the SHIN3 cells both in vitro and in vivo to
      kill the cell using (157/155)Gd with external irradiation with an appropriate
      neutron beam while monitoring with MRI. Thus, Av-G6Gd may be a promising agent
      for Gd neutron capture therapy of peritoneal carcinomatosis. This reagent also
      has the potential to permit monitoring of its pharmacokinetic progress with MRI.

PMID- 11459465
TI  - Fluorescent gramicidin derivatives for single-molecule fluorescence and ion
      channel measurements.
AB  - Single-molecule spectroscopies in combination with single-channel patch-clamp
      measurements have the potential for providing new information on ion channel
      gating processes. Fluorescent gramicidin derivatives could provide a means for
      calibrating such experiments since the structure of the open channel is known and
      the mechanism of gating (peptide dimerization) is generally agreed. We describe
      here the synthesis and characterization of two pairs of gramicidin derivatives
      that should prove useful for such studies. They contain robust fluorophores,
      undergo resonance energy transfer (FRET) when they dimerize, and have single
      channel properties close to those of the wild-type channel.

PMID- 11459466
TI  - Design and synthesis of substrate and internal standard conjugates for profiling
      enzyme activity in the Sanfilippo syndrome by affinity
      chromatography/electrospray ionization mass spectrometry.
AB  - We describe the design and synthesis of substrate and internal standard
      conjugates for application in profiling enzyme activity of the enzymes alpha-D-2
      deoxy-2-N-sulfonamido-glucosamine sulfamidase, alpha-D-2-deoxy-2-N-acetyl
      glucosamine hydrolase, acetyl-coenzymeA:alpha-D-2-deoxy-2-amino-glucosamine
      transferase, and alpha-D-2-deoxy-2-N-acetyl-glucosamine-6-sulfate sulfatase.
      Deficiency of any one of these enzymes results in a single clinical phenotype
      known as Sanfilippo syndrome. Such substrates have been proven effective in the
      confirmation of enzyme deficiency by a combination of affinity chromatography
      (AC) and electrospray ionization mass spectrometry (ESIMS), which forms the
      foundation for a new analytical technology (ACESIMS) of general interest and
      application to clinical and biomedical research.

PMID- 11459467
TI  - Biotin reagents for antibody pretargeting. 5. Additional studies of biotin
      conjugate design to provide biotinidase stability.
AB  - An investigation was conducted in which the stabilities of four structurally
      different biotin derivatives were assessed with regard to biotinamide bond
      hydrolysis by the enzyme biotinidase. The biotin derivatives studied contained an
      extra methylene in the valeric acid chain of biotin (i.e., homobiotin), or
      contained conjugated amino acids having hydroxymethylene, carboxylate, or acetate
      functionalities on a methylene alpha to the biotinamide bond. The biotinidase
      hydrolysis assay was conducted on biotin derivatives that were radioiodinated at
      high specific activity, and then subjected to diluted human serum at 37 degrees C
      for 2 h. After incubation, assessment of biotinamide bond hydrolysis by
      biotinidase was readily achieved by measuring the percentage of radioactivity
      that did not bind with avidin. As controls, an unsubstituted biotin derivative
      which is rapidly cleaved by biotinidase and an N-methyl-substituted biotin
      derivative which is stable to biotinidase cleavage were included in the study.
      The results indicate that increasing the distance from the biotin ring structure
      to the biotinamide bond by one methylene only decreases the rate of biotinidase
      cleavage, but does not block it. The data obtained also indicate that placing a
      hydroxymethylene, carboxylate, or acetate alpha to the biotinamide bond is
      effective in blocking the biotinamide hydrolysis reaction. These data, in
      combination with data previously obtained, which indicate that biotin derivatives
      containing hydroxymethylene or carboxylate moieties retain the slow dissociation
      rate of biotin from avidin and streptavidin [Wilbur, D. S., et al. (2000)
      Bioconjugate Chem. 11, 569-583], strongly support incorporation of these
      structural features into biotin derivatives being used for in vivo targeting
      applications.

PMID- 11459468
TI  - 99mTc-labeling of a hydrazinonicotinamide-conjugated vitronectin receptor
      antagonist useful for imaging tumors.
AB  - This report describes the (99m)Tc labeling of a HYNIC-conjugated vitronectin
      receptor antagonist (SQ168 = [2-[[[5-[carboonyl]-2
      pyridinyl]hydrazono]methyl]benzenesulfonic acid]-Glu(cyclo[Lys-Arg-Gly-Asp-D
      Phe])-cyclo[Lys-Arg-Gly-Asp-D-Phe]). The ternary ligand complex
      [(99m)Tc(SQ168)(tricine)(TPPTS)] (RP593) was prepared using a non-SnCl(2)
      containing formulation. The corresponding (99)Tc analogue, [(99)Tc]RP593, was
      also prepared and characterized by HPLC and LC-MS. A HPLC concordance experiment
      using RP593 and [(99)Tc]RP593 showed that the same technetium complex was
      prepared at both the tracer and macroscopic levels. The LC-MS data is completely
      consistent with the 1:1:1:1 composition for Tc:SQ168:tricine:TPPTS and provides
      direct evidence that the two radiometric peaks in the radio-HPLC chromatogram of
      RP593 are indeed due to the resolution of diastereomers. In an in vitro receptor
      binding assay, [(99)Tc]RP593 was shown to have comparable binding affinity for
      the vitronectin receptor to that of SQ168 itself.

PMID- 11459469
TI  - Synthesis and characterization of two (111)In-labeled DTPA-peptide conjugates.
AB  - This report describes the synthesis and characterization of two (111)In-labeled
      DTPA-peptide conjugates (DTPA-MA and DTPA-BA). It is surprising to find that
      (111)In(DTPA-MA) and (111)In(DTPA-BA) are more hydrophilic than their
      corresponding (90)Y analogues, suggesting a different coordination sphere in
      (111)In and(90)Y complexes of the same DTPA-peptide conjugate. By a reversed
      phase HPLC method, both (111)In(DTPA-MA) and (111)In(DTPA-BA) showed only one
      radiometric peak in their respective HPLC chromatogram due to a rapid
      interconversion of different isomers (particularly cis and trans isomers for
      (111)In(DTPA-MA); cis-cis, cis-trans, trans-cis, and trans-trans isomers for
      (111)In(DTPA-BA)). The interconversion of different isomers involves the
      "wagging" of the diethylenetriamine backbone, "shuffling" of the NO or NO(2)
      donor sets, and a rapid inversion at the terminal amine-nitrogen atoms.

PMID- 11459470
TI  - Nucleosides and nucleotides. 208. Alternate-strand triple-helix formation by the
      3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction
      point.
AB  - The synthesis of 3'-3'-linked oligodeoxynucleotides (ODNs) with the
      anthraquinonyl group at the junction point is described. The ODNs were
      synthesized on a DNA synthesizer using a controlled pore glass (CPG) carrying
      pentaerythritol that has an intercalator at one of the four hydroxymethyl groups.
      Stability of the triplexes with the target duplexes was studied by thermal
      denaturation. The 3'-3'-linked ODNs with the anthraquinonyl group enhanced the
      thermal stability of the triplexes when compared with those without the
      intercalator and the unmodified nonamer 10. It was found that the ODNs 12 and 13
      carrying the anthraquinonyl groups can form thermally stable triplexes by
      skipping two or three extra base pairs between two binding domains of the target
      duplexes. The ability of the 3'-3'-linked ODNs to inhibit cleavage of the target
      DNA 22 by the restriction enzyme Hind III was tested. It was found that the 3'-3'
      linked ODN 16 with the anthraquinonyl group at the junction point inhibited the
      cleavage by the enzyme more effectively than the nonamer 14 and the 3'-3'-linked
      ODN 15 without the intercalator.

PMID- 11459471
TI  - Synthesis and characterization of a ruthenium(II)-based redox conjugate for
      reagentless biosensing.
AB  - Synthesis of a novel sulfhydryl-specific, tetraammine Ru(II)polypyridyl complex,
      [Ru(II)(NH(3))(4)(1,10-phenanthroline-5-maleimide)](PF(6))(2), which exhibits
      environment-sensitive electrochemical properties is described. When conjugated to
      an allosteric site in a genetically engineered mutant of maltose binding protein,
      the formal potential of the conjugated redox probe is shifted to higher potential
      upon maltose binding. The magnitude of this potential shift was used to measure
      maltose affinity of the protein-redox conjugate complex and to monitor maltose
      concentration in solution. These results are presented in context of reagentless
      biosensing.

PMID- 11459472
TI  - Photoreduction of autooxidized albumin-heme hybrid in saline solution: revival of
      its O(2)-binding ability.
AB  - Recombinant human serum albumin (rHSA) incorporating 2-[8-[N-(2
      methylimidazolyl)]octanoyloxymethyl]-5,10,15,20-tetrakis(alpha,alpha,alpha,alpha
      o-pivalamido)phenylporphinatoiron(II)s (Fe(II)Ps) [rHSA-Fe(II)P] is a synthetic
      hemoprotein which can bind and release O(2) reversibly under physiological
      conditions (saline solution [NaCl]: 150 mM, pH 7.3) as do hemoglobin and
      myoglobin. However, the central ferrous ions of Fe(II)Ps are slowly oxidized to
      O(2)-inactive ferric forms. Based on the UV-vis. absorption spectroscopy, the
      majority of the autooxidized Fe(III)Ps in albumin are determined to be six
      coordinate high-spin complexes with a proximal imidazole and a chloride anion,
      which show ligand-to-metal charge transfer (LMCT) absorption at 330 nm.
      Interestingly, photoirradiation of this LMCT band under an argon atmosphere led
      to reduction of the central ferric iron of Fe(III)P, allowing the revival of the
      O(2)-binding ability. The ratio of the photoreduction reached a maximum of 83%,
      which is probably due to the partial dissociation of the axial imidazole. The
      same photoirradiation under a CO atmosphere provides the corresponding carbonyl
      rHSA-Fe(II)P. Laser flash photolysis experiments revealed that the reduction was
      completed within 100 ns. The quantum yields (Phi) of these photoreductions were
      approximately 0.01.

PMID- 11459474
TI  - Self-encapsulation of poly-2,7-fluorenes in a dendrimer matrix.
AB  - The synthesis and characterization of complex dendritic, rigid rod poly-2,7
      fluorene homopolymers and copolymers via a macromonomer approach is reported.
      Several 2,7-dibromofluorene monomers containing benzyl ether dendrons
      (generations 1, 2, and 3) in the 9,9'-position of the fluorene ring were prepared
      and employed in condensation polymerizations to yield both homopolymers and
      copolymers with diethylhexylfluorene. Fluorescence measurements of the materials
      reveal extensive conjugation along the polymer backbone. The determination of the
      solid-state PL spectra and quantum efficiencies showed that there is an apparent
      optimum size of the dendritic side groups with the [G-2]-derivatives showing high
      reactivity with associated site isolation of the conjugated chain. AFM analysis
      and DSC results confirmed that the hybrid polymers and copolymers did not show
      any sign of a microphase-separated morphology. First EL-results demonstrated that
      the homopolymers have higher turn-on voltages then the corresponding copolymers.

PMID- 11459475
TI  - Active site structure and mechanism of human glyoxalase I-an ab initio
      theoretical study.
AB  - The structure of the active site of human glyoxalase I and the reaction mechanism
      of the enzyme-catalyzed conversion of the thiohemiacetal, formed from
      methylglyoxal and glutathione, to S-D-lactoylglutathione has been investigated by
      ab initio quantum chemical calculations. To realistically represent the
      environment of the reaction center, the effective fragment potential methodology
      has been employed, which allows systems of several hundred atoms to be described
      quantum mechanically. The methodology and the active site model have been
      validated by optimizing the structure of a known enzyme-inhibitor complex, which
      yielded structures in good agreement with the experiment. The same crystal
      structure has been used to obtain the quantum motif for the investigation of the
      glyoxalase I reaction. The results of our study confirm that the metal center of
      the active site zinc complex plays a direct catalytic role by binding the
      substrate and stabilizing the proposed enediolate reaction intermediate. In
      addition, our calculations yielded detailed information about the interactions of
      the substrate, the reaction intermediates, and the product with the active site
      of the enzyme and about the mechanism of the glyoxalase I reaction. The proton
      transfers of the reaction proceed via the two highly flexible residues Glu172 and
      Glu99. Information about the structural and energetic effect of the protein on
      the first-shell complex has been attained by comparison of the structures
      optimized in the local protein environment and in a vacuum. The environment of
      the zinc complex disturbs the Cs symmetry found for the complex in a vacuum,
      which suggests an explanation for the stereochemical behavior of glyoxalase I.

PMID- 11459476
TI  - The total synthesis of lipid I.
AB  - A total synthesis of lipid I (4), a membrane-associated intermediate in the
      bacterial cell wall (peptidoglycan) biosynthesis pathway, is reported. This
      highly convergent synthesis will enable further studies on bacterial resistance
      mechanisms and may provide insight toward the development of new chemotherapeutic
      agents with novel modes of action.

PMID- 11459477
TI  - A versatile catalyst for Heck reactions of aryl chlorides and aryl bromides under
      mild conditions.
AB  - In the presence of Cy2NMe, Pd/P(t-Bu)3 serves as an exceptionally mild and
      versatile catalyst for Heck reactions of aryl chlorides and bromides. A
      sterically and electronically diverse array of aryl bromides, as well as
      activated aryl chlorides, couple with a range of mono- and disubstituted olefins
      at room temperature, furnishing the arylated product with high E/Z
      stereoselection. The corresponding reactions of a broad spectrum of electron
      neutral and electron-rich aryl chlorides proceed at elevated temperature, also
      with high selectivity. In terms of scope and mildness, Pd/P(t-Bu)3/Cy2NMe
      represents an advance over previously reported catalysts for these Heck coupling
      processes.

PMID- 11459478
TI  - Enantioselective fluorination mediated by cinchona alkaloid
      derivatives/Selectfluor combinations: reaction scope and structural information
      for N-fluorocinchona alkaloids.
AB  - Cinchona-alkaloid/Selectfluor combinations efficiently fluorinate a variety of
      carbonyl compounds in a highly enantioselective manner to furnish chiral alpha
      fluorocarbonyl compounds. The DHQB/Selectfluor combination is effective for the
      enantioselective fluorination of indanones and tetralones 1 in up to 91% ee. The
      first enantioselective syntheses of chiral derivatizing reagents 3 was
      accomplished with high ee and in high chemical yields by the DHQDA/Selectfluor
      combination. 3-Fluorooxindoles 7 were prepared with ee up to 83% using the
      (DHQ)2AQN/Selectfluor or the (DHQD)2PYR/Selectfluor combination. Since the
      combinations are conveniently prepared in situ from readily available reagents,
      the present system represents a practical method for enantioselective
      fluorination. X-ray crystallography and 1H NMR analyses of the cinchona
      alkaloids/Selectfluor combination have established that the species that mediate
      this novel reaction are N-fluoroammonium cinchona alkaloid tetrafluoroborates,
      which adopt open conformations.

PMID- 11459479
TI  - Synthesis and characterization of dimensionally ordered semiconductor nanowires
      within mesoporous silica.
AB  - Semiconductor nanowires of silicon have been synthesized within the pores of
      mesoporous silica using a novel supercritical fluid solution-phase approach.
      Mesoporous silica, formed by the hydrolysis of tetramethoxysilane (TMOS) in the
      presence of a triblock copolymer surfactant, was employed for the nucleation and
      growth of quantum-confined nanowires. The filling of the silica mesopores with
      crystalline silicon and the anchoring of these nanowires to the sides of the
      pores were confirmed by several techniques including electron microscopy, powder
      X-ray diffraction, 29Si magic angle spinning nuclear magnetic resonance, infrared
      spectroscopy, and X-ray fluorescence. Effectively, the silica matrix provides a
      means of producing a high density of stable, well-ordered arrays of semiconductor
      nanowires in a low dielectric medium. The ordered arrays of silicon nanowires
      also exhibited discrete electronic and photoluminescence transitions that could
      be exploited in a number of applications, including nanodevices and
      interconnects.

PMID- 11459480
TI  - Rational reprogramming of the R2 subunit of Escherichia coli ribonucleotide
      reductase into a self-hydroxylating monooxygenase.
AB  - The outcome of O2 activation at the diiron(II) cluster in the R2 subunit of
      Escherichia coli (class I) ribonucleotide reductase has been rationally altered
      from the normal tyrosyl radical (Y122*) production to self-hydroxylation of a
      phenylalanine side-chain by two amino acid substitutions that leave intact the
      (histidine)2-(carboxylate)4 ligand set characteristic of the diiron-carboxylate
      family. Iron ligand Asp (D) 84 was replaced with Glu (E), the amino acid found in
      the cognate position of the structurally similar diiron-carboxylate protein,
      methane monooxygenase hydroxylase (MMOH). We previously showed that this
      substitution allows accumulation of a mu-1,2-peroxodiiron(III) intermediate,
      which does not accumulate in the wild-type (wt) protein and is probably a
      structural homologue of intermediate P (H(peroxo)) in O2 activation by MMOH. In
      addition, the near-surface residue Trp (W) 48 was replaced with Phe (F), blocking
      transfer of the "extra" electron that occurs in wt R2 during formation of the
      formally Fe(III)Fe(IV) cluster X. Decay of the mu-1,2-peroxodiiron(III) complex
      in R2-W48F/D84E gives an initial brown product, which contains very little Y122*
      and which converts very slowly (t1/2 approximately 7 h) upon incubation at 0
      degrees C to an intensely purple final product. X-ray crystallographic analysis
      of the purple product indicates that F208 has undergone epsilon-hydroxylation and
      the resulting phenol has shifted significantly to become a ligand to Fe2 of the
      diiron cluster. Resonance Raman (RR) spectra of the purple product generated with
      16O2 or 18O2 show appropriate isotopic sensitivity in bands assigned to O-phenyl
      and Fe-O-phenyl vibrational modes, confirming that the oxygen of the Fe(III)
      phenolate species is derived from O2. Chemical analysis, experiments involving
      interception of the hydroxylating intermediate with exogenous reductant, and
      Mossbauer and EXAFS characterization of the brown and purple species establish
      that F208 hydroxylation occurs during decay of the peroxo complex and formation
      of the initial brown product. The slow transition to the purple Fe(III)-phenolate
      species is ascribed to a ligand rearrangement in which mu-O2- is lost and the
      F208-derived phenolate coordinates. The reprogramming to F208 monooxygenase
      requires both amino acid substitutions, as very little epsilon
      hydroxyphenylalanine is formed and pathways leading to Y122* formation
      predominate in both R2-D84E and R2-W48F.

PMID- 11459481
TI  - Mn K-edge XANES and Kbeta XES studies of two Mn-oxo binuclear complexes:
      investigation of three different oxidation states relevant to the oxygen-evolving
      complex of photosystem II.
AB  - Two structurally homologous Mn compounds in different oxidation states were
      studied to investigate the relative influence of oxidation state and ligand
      environment on Mn K-edge X-ray absorption near-edge structure (XANES) and Mn
      Kbeta X-ray emission spectroscopy (Kbeta XES). The two manganese compounds are
      the di-mu-oxo compound [L'2Mn(III)O2Mn(IV)L'2](ClO4)3, where L' is 1,10
      phenanthroline (Cooper, S. R.; Calvin, M. J. Am. Chem. Soc. 1977, 99, 6623-6630)
      and the linear mono-mu-oxo compound [LMn(III)OMn(III)L](ClO4)2, where L- is the
      monoanionic N,N-bis(2-pyridylmethyl)-N'-salicylidene-1,2-diaminoethane ligand
      (Horner, O.; Anxolabehere-Mallart, E.; Charlot, M. F.; Tchertanov, L.; Guilhem,
      J.; Mattioli, T. A.; Boussac, A.; Girerd, J.-J. Inorg. Chem. 1999, 38, 1222
      1232). Preparative bulk electrolysis in acetonitrile was used to obtain higher
      oxidation states of the compounds: the Mn(IV)Mn(IV) species for the di-mu-oxo
      compound and the Mn(III)Mn(IV) and Mn(IV)Mn(IV) species for the mono-mu-oxo
      compound. IR, UV/vis, EPR, and EXAFS spectra were used to determine the purity
      and integrity of the various sample solutions. The Mn K-edge XANES spectra shift
      to higher energy upon oxidation when the ligand environment remains similar.
      However, shifts in energy are also observed when only the ligand environment is
      altered. This is achieved by comparing the di-mu-oxo and linear mono-mu-oxo Mn-Mn
      moieties in equivalent oxidation states, which represent major structural
      changes. The magnitude of an energy shift due to major changes in ligand
      environment can be as large as that of an oxidation-state change. Therefore, care
      must be exercised when correlating the Mn K-edge energies to manganese oxidation
      states without taking into account the nature of the ligand environment and the
      overall structure of the compound. In contrast to Mn K-edge XANES, Kbeta XES
      spectra show less dependence on ligand environment. The Kbeta1,3 peak energies
      are comparable for the di-mu-oxo and mono-mu-oxo compounds in equivalent
      oxidation states. The energy shifts observed due to oxidation are also similar
      for the two different compounds. The study of the different behavior of the XANES
      pre-edge and main-edge features in conjunction with Kbeta XES provides
      significant information about the oxidation state and character of the ligand
      environment of manganese atoms.

PMID- 11459482
TI  - Cubic aluminum silicides RE8Ru12Al49Si9(Al(x)Si12-x) (RE = Pr, Sm) from liquid
      aluminum. Empty (Si,Al)12 cuboctahedral clusters and assignment of the Al/Si
      distribution with neutron diffraction.
AB  - Two new quaternary aluminum silicides, RE8Ru12Al49Si9(Al(x)Si12-x) (x
      approximately 4; RE = Pr, Sm), have been synthesized from Sm (or Sm2O3), Pr, Ru,
      and Si in molten aluminum between 800 and 1000 degrees C in sealed fused silica
      tubes. Both compounds form black shiny crystals that are stable in air and NaOH.
      The Nd analog is also stable. The compounds crystallize in a new structural type.
      The structure, determined by single-crystal X-ray diffraction, is cubic, space
      group Pm3m with Z = 1, and has lattice parameters of a = 11.510(1) A for
      Sm8Ru12Al49Si9(Al(x)Si12-x) and a = 11.553(2) A for Pr8Ru12Al49Si9(Al(x)Si12-x)
      (x approximately 4). The structure consists of octahedral units of AlSi6, at the
      cell center, Si2Ru4Al8 clusters, at each face center, SiAl8 cubes, at the middle
      of the cell edges, and unique (Al,Si)12 cuboctohedral clusters, at the cell
      corners. These different structural units are connected to each other either by
      shared atoms, Al-Al bonds, or Al-Ru bonds. The rare earth metal atoms fill the
      space between various structural units. The Al/Si distribution was verified by
      single-crystal neutron diffraction studies conducted on Pr8Ru12Al49Si9(Al(x)Si12
      x). Sm8Ru12Al49Si9(Al(x)Si12-x) and Pr8Ru12Al49Si9(Al(x)Si12-x) show
      ferromagnetic ordering at Tc approximately 10 and approximately 20 K,
      respectively. A charge of 3+ can be assigned to the rare earth atoms while the Ru
      atoms are diamagnetic.

PMID- 11459483
TI  - The dynamics of electron self-exchange between nanoparticles.
AB  - The rate of electron self-exchange reactions between discretely charged metal
      like cores of nanoparticles has been measured in multilayer films of
      nanoparticles by an electrochemical method. The nanoparticles are Au monolayer
      protected clusters with mixed monolayers of hexanethiolate and mercaptoundecanoic
      acid ligands, linked to each other and to the Au electrode surface with
      carboxylate-metal ion-carboxylate bridges. Cyclic voltammetry of the nanoparticle
      films exhibits a series of well-defined peaks for the sequential, single
      electron, double-layer charging of the 1.6-nm-diameter Au cores. The electron
      self-exchange is measured as a diffusion-like electron-hopping process, much as
      in previous studies of redox polymer films on electrodes. The average electron
      diffusion coefficient is DE = 10(+/-5) x 10(-8) cm2/s, with no discernible
      dependence on the state of charge of the nanoparticles or on whether the reaction
      increases or decreases the core charge. This diffusion constant corresponds to an
      average first-order rate constant kHOP of 2(+/-1) x 10(6) s(-1) and an average
      self-exchange rate constant, kEX, of 2(+/-1) x 10(8) M(-1) x s(-1), using a cubic
      lattice hopping model. This is a very large rate constant, considering the
      nominally lengthy linking bridge between the Au cores.

PMID- 11459484
TI  - Stereochemical, structural, and thermodynamic origins of stability differences
      between stereoisomeric benzo[a]pyrene diol epoxide deoxyadenosine adducts in a
      DNA mutational hot spot sequence.
AB  - Benzo[a]pyrene (BP), a prototype polycyclic aromatic hydrocarbon (PAH), can be
      metabolically activated to the enantiomeric benzo[a]pyrene diol epoxides (BPDEs),
      (+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and
      the (-)-(7S,8R,9R,10S) enantiomer. These can react with adenine residues in DNA,
      to produce the stereoisomeric 10S (+)- and 10R (-)-trans-anti-[BP]-N(6)-dA
      adducts. High-resolution NMR solution studies indicate that in DNA duplexes the
      10R (-) adduct is intercalated on the 5'-side of the modified adenine, while the
      10S (+) adduct is disordered, exhibits multiple adduct conformations, and is
      positioned on the 3'-side of the modified adenine. Duplexes containing the 10S
      (+) adduct positioned at A within codon 61 of the human N-ras sequence CAA are
      thermodynamically less stable and more easily excised by human DNA repair enzymes
      than those containing the 10R (-) adduct. However, the molecular origins of these
      differences are not understood and represent a fascinating opportunity for
      elucidating structure-function relationships. We have carried out a computational
      investigation to uncover the structural and thermodynamic origins of these
      effects in the 11-mer duplex sequence d(CGGACAAGAAG).d(CTTCTTGTCCG) by performing
      a 2-ns molecular dynamics simulation using NMR solution structures as the basis
      for the starting models. Then, we applied the MM-PBSA (molecular mechanics
      Poisson-Boltzmann surface area) method to compute free energy differences between
      the stereoisomeric adducts. The 10R (-) isomer is more stable by approximately 13
      kcal/mol, of which approximately 10 kcal/mol is enthalpic, which agrees quite
      well with their observed differences in thermodynamic stability. The lower
      stability of the 10S (+) adduct is due to diminished stacking by the BP moiety in
      the intercalation pocket, more helix unwinding, and a diminished quality of
      Watson-Crick base pairing. The latter stems from conformational heterogeneity
      involving a syn-anti equilibrium of the glycosidic bond in the modified adenine
      residue. The lower stability and conformational heterogeneity of the 10S (+)
      adduct may play a role in its enhanced susceptibility to nucleotide excision
      repair.

PMID- 11459485
TI  - Quantum yields of luminescent lanthanide chelates and far-red dyes measured by
      resonance energy transfer.
AB  - Luminescent lanthanide chelates have unusual spectroscopic characteristics that
      make them valuable alternative probes to conventional organic fluorophores.
      However, fundamental parameters such as their quantum yield, and radiative and
      nonradiative decay rates have been difficult or impossible to measure. We have
      developed a simple and robust method based on resonance energy transfer to
      accurately measure these parameters. In addition, the excitation/emission process
      in lanthanide chelates involves several steps, and we are able to quantify each
      step. These include excitation of an organic antenna, transfer of energy from the
      antenna to lanthanide, and then lanthanide emission. Overall, the parameters show
      that lanthanide chelates can be efficient long-lived emitters, making them
      sensitive detection reagents and excellent donors in resonance energy transfer.
      The method is also shown to be applicable to photophysical characterization of
      red-emitting dyes, which are difficult to characterize by conventional means.

PMID- 11459486
TI  - Laser flash photolysis study of Jacobsen catalyst and related manganese(III)
      salen complexes. Relevance to catalysis.
AB  - The laser flash photolysis and emission properties of a set of five-coordinate
      manganese(III) Schiff-base complexes have been examined. In contrast to the
      intramolecular electron transfer between Mn3+ and the equatorial salen ligand
      reported to occur in the absence of axial coordination, our laser flash
      photolysis study has shown that the reactivity of the respective excited states
      is appreciably influenced by the electron donor strength of the apical ligand at
      the metal center. In fact, homolytic and heterolytic photocleavage of the metal
      ligand apical bond can be the most important processes upon laser excitation,
      their relative contribution being influenced by medium effects and the sigma
      charge donation of the axial ligand. On the other hand, the detection of reactive
      intermediates such as the oxomanganese(V) salen complex (lambda(max) 530 nm) by
      laser flash photolysis opens the way to apply this fast detection technique to
      the study of reaction mechanisms in catalysis by metallic complexes. As a matter
      of fact, quenching of oxomanganese(V) salen by simple alkenes has been observed
      by laser flash.

PMID- 11459487
TI  - Self-consistent Karplus parametrization of 3J couplings depending on the
      polypeptide side-chain torsion chi1.
AB  - Recently proposed self-consistent 3J coupling analysis (Schmidt, J. M.; Blumel,
      M.; Lohr, F.; Ruterjans, H. J. Biomol. NMR 1999, 14, 1-12) has been carried out
      to calibrate Karplus parameters constituting the empirical dependence of 3J
      coupling constants on the chi1 dihedral angle in amino acid side chains. The
      procedure involves simultaneous least-squares optimization of six sets of three
      Karplus coefficients related to all six 3J coupling types accessible in 15N,13C
      labeled proteins. A simple concept of fundamental and incremental component
      couplings is proposed to account for substituent effects, eventually yielding
      amino acid topology-specific Karplus parameters. The method is exemplified with
      recombinant Desulfovibrio vulgaris flavodoxin (147 amino acids, 16 kDa) with
      reference to a total of 749 experimental 3JHalpha,Hbeta, 3JN',Hbeta, 3JC',Hbeta,
      3JHalpha,Cgamma, 3JN',Cgamma, and 3JC',Cgamma coupling constants. Unlike other
      parametrizations, the present method does not make reference to X-ray
      coordinates, so that the Karplus coefficients obtained are not influenced by
      differences between solution and crystal states. Cross validation using X-ray
      torsion angles demonstrates the improvement relative to previous
      parametrizations. The Karplus coefficients derived are applicable to other
      proteins, too. Parameter refinement also yields a series of chi1 torsion angles,
      providing valuable constraints for protein structure determination, as well as
      optional parameters of local angular mobility in the contexts of Gaussian random
      fluctuation or a three-site jump model. The procedure permits automatic
      stereospecific assignments of Hbeta and Cgamma chemical shifts. The majority of
      the flavodoxin side-chain conformations agrees with high-resolution X-ray
      structures of the protein. Marked deviations between NMR and X-ray datasets are
      attributed to different rotameric states due to crystal-packing effects and to
      conformational equilibria between multiple chi1 rotamers.

PMID- 11459488
TI  - A new mechanism for spin--lattice relaxation of heavy nuclei in the solid state:
      207Pb relaxation in lead nitrate.
AB  - A detailed investigation of the spin-lattice relaxation time, T1, for 207Pb in
      solid lead nitrate has been undertaken in an effort to understand the mechanism
      of relaxation. The results show that the 207Pb T1 is independent of magnetic
      field strength and inversely proportional to the square of the temperature. These
      are signatures of relaxation by a spin-phonon Raman scattering mechanism. Nuclear
      spin-lattice relaxation in solid lead salts is more efficient for sites with
      smaller magnetic shielding anisotropy. A coupling mechanism is proposed whereby
      phonons create a local magnetic field by modulating the valence electron shell
      motion relative to the nuclear/electron core. Literature data suggest that spin
      phonon scattering is a common relaxation pathway for other spin-1/2 heavy nuclei
      in solids.

PMID- 11459489
TI  - Ultrafast dynamics of cyclohexene and cyclohexene-d10 excited at 200 nm.
AB  - By exciting cyclohexene in the gas phase at 200 nm and probing it by nonresonant
      multiphoton ionization with mass-selective detection of the ion yields, we found
      four time constants tau(i) (20, 47, 43, 350 fs). Whereas deuteration lengthens
      tau2 by a factor of 1.4, the other constants do not change. Tau1-tau3 represent
      traveling times through observation windows on excited surfaces, whereas tau4
      reflects a process in the hot ground state. We assign tau1 (20 fs) to departure
      from the Franck-Condon regions of the Rydberg and pipi* states, which are both
      populated at 200 nm, and tau2 (47 fs) to traveling along the pipi* surface and
      suggest that a [1,3]-sigmatropic H shift begins in this state. This rationalizes
      the deuterium effect on tau2. To explain why this window is followed by a process
      not subject to a D effect, we postulate that the pipi surface is crossed late
      (i.e., at low energy) by the zwitterionic state Z and that formation of a carbene
      (the known photochemical product, cyclopentylcarbene) begins there. The
      corresponding 1,2-shift of a CC bond is then (within tau4 = 350 fs) largely
      reversed on the ground-state surface, while a smaller part of the carbene forms
      products such as methylenecyclopentane within the same time. Carbene formation is
      probably accompanied by some cis-trans isomerization. The wavelength dependence
      of carbene formation is attributed to a memory for the initially excited state,
      based on momentum conservation. The processes are most likely typical of simple
      olefins. The fragmentation pattern showed that butadiene is not formed until at
      least 500 ps. The retro-Diels-Alder reaction, known to take place in the ground
      state, thus only occurs later.

PMID- 11459490
TI  - Temperature and viscosity dependence in the stereoselective formation of the
      inverted housane for the photochemical nitrogen loss from the deuterium
      stereolabeled parent diazabicyclo[2.2.1]hept-2-ene.
AB  - For the liquid-phase photolytic denitrogenation of the stereolabeled DBH
      derivative exo-d2-diazabicyclo[2.2.1]heptene (exo-d2-1), the k(inv)/k(ret) ratio
      of the inverted [2(inv)] and retained [2(ret)] housanes (bicyclo[2.1.0]pentanes)
      depends on the viscosity of the medium. For this purpose, the viscosity was
      varied by changing the solvent (various alcohols and diols, n-hexane, and
      acetonitrile) at constant temperature and by changing the temperature (-50 to
      +100 degrees C) in one single solvent, namely n-butanol. This viscosity effect is
      consistent with a stepwise denitrogenation mechanism in the liquid-phase
      photolysis of DBH, which proceeds through an unsymmetrical, nitrogen-containing
      transient, namely the singlet diazenyl diradical. The simple free-volume model
      adequately accounts for the observed viscosity behavior of the k(inv)/k(ret)
      ratio in terms of frictional effects. The temperature dependence discloses a
      small but measurable difference in the internal activation energies for the
      inversion and retention processes of the proposed diazenyl diradical.

PMID- 11459491
TI  - Interplay of intrinsic and environmental effects on the magnetic properties of
      free radicals issuing from H-atom addition to cytosine.
AB  - Possible radical reaction products issuing from H-atom addition to cytosine have
      been characterized and analyzed by means of a comprehensive quantum mechanical
      approach including density functional computations (B3LYP), together with
      simulation of the solvent by the polarizable continuum model (PCM), and averaging
      of spectroscopic properties over the most important vibrational motions. The
      hyperfine couplings of the semirigid 5,6-dihydrocytos-6yl radical computed at the
      optimized geometry are in good agreement with their experimental counterparts. On
      the other hand, vibrational averaging is mandatory for obtaining an effectively
      planar structure for the 5,6-dihydrocytos-5yl radical with the consequent
      equivalence of beta-hydrogens. Finally, only proper consideration of
      environmental effects restores the agreement between computed and experimental
      couplings for the base anion protonated at N3.

PMID- 11459492
TI  - Investigation of sodium cations in dehydrated zeolites LSX, X, and Y by 23Na off
      resonance RIACT triple-quantum and high-speed MAS NMR spectroscopy.
AB  - We investigated by two-dimensional 23Na ORIACT MQMAS NMR and one-dimensional 23Na
      high-speed MAS NMR spectroscopy a homologous series of dehydrated zeolites with
      faujasite structure. The framework silicon to aluminum ratios varied between 1.06
      and 2.60. In the case of zeolites Y (nSi/nAl = 2.60), we studied materials with
      sodium exchange degrees between 0 and 95%. The recently introduced ORIACT method
      (Caldarelli, S.; Ziarelli, F. J. Am. Chem. Soc. 2000, 122, 12015) significantly
      improved the resolution of the MQMAS spectra, in comparison with earlier studies.
      It was thus possible to extract meaningful quadrupole parameters by MQMAS NMR,
      which were used as a starting point for the simulation of 1D MAS NMR spectra to
      obtain more accurate values of the NMR parameters and site occupancy. We were
      able to show by this approach that in zeolite NaLSX the SI positions in the
      hexagonal prisms are occupied by sodium cations. For the homologous series of
      zeolites Y, it was found that sodium cations located at SII positions are the
      easiest to be substituted by ammonium ions through the exchange process.

PMID- 11459493
TI  - Photoswitched singlet energy transfer in a porphyrin-spiropyran dyad.
AB  - A photochromic nitrospiropyran moiety (Sp) has been covalently linked to a zinc
      (PZn) and to a free-base (P(H2)) porphyrin. In the resulting dyads (P(Zn)-Sp(c)
      and P(H2)-Sp(c)), the porphyrin first excited singlet states are unperturbed by
      the closed form of the attached spiropyran. Excitation of the spiropyran moiety
      of either dyad in the near-UV region results in ring opening to a merocyanine
      form (P-Sp(o)) that absorbs at 600 nm. The open form re-closes thermally in 2
      methyltetrahydrofuran with a time constant of 20 s, or following irradiation into
      the 600 nm band. Excitation of the zinc porphyrin moiety in the merocyanine form
      of the dyad yields 1PZn-Sp(o). The lifetime of the zinc porphyrin excited state
      is reduced from its usual value of 1.8 ns to 130 ps by singlet-singlet energy
      transfer to the merocyanine moiety to give PZn-1Sp(o). The quantum yield of
      energy transfer is 0.93. Quenching is also observed in the free base dyad, where
      1P(H2)-Sp(o) and P(H2)-1Sp(o) exchange singlet excitation energy. This
      photoswitchable quenching phenomenon provides light-activated control of the
      porphyrin excited states, and consequently control of any subsequent energy or
      electron-transfer processes that might be initiated by these excited states in
      more complex molecular photonic or optoelectronic devices.

PMID- 11459494
TI  - A theoretical study of the effect of a tetraalkylammonium counterion on the
      hydrogen bond strength in Z-hydrogen maleate.
AB  - High-level ab initio calculations (B3LYP/6-31+G and QCISD(T)/6-311+G**) were
      carried out to resolve the disagreement between recent experimental and
      computational estimates of the relative strength of the intramolecular hydrogen
      bond in Z-hydrogen maleate anion with respect to the normal hydrogen bond in
      maleic acid. The computational estimates for the strength of the intramolecular
      hydrogen bond in the gas-phase maleate anion are in a range of 14-28 kcal/mol
      depending on the choice of the reference structure. Computational data suggest
      that the electrostatic influence of a counterion such as a tetraalkylammonium
      cation can considerably weaken the hydrogen bonding interaction (by 1.5-2 times)
      in the complexed hydrogen maleate anion relative to that in the naked anion. The
      estimated internal H-bonding energies for a series of Z-maleate/R4N+ salts (R =
      CH3, C2H5, CH3CH2CH2CH2) range from 8 to 13 kcal/mol. The calculated energy
      differences between the E- and Z-hydrogen maleates complexed to Me4N+, Et4N+, and
      Bu4N+ cation are 4.9 (B3LYP/6-31+G(d,p)) and 5.7 and 5.8 kcal/mol (B3LYP/6
      31G(d)). It is also demonstrated that the sodium cation exerts a similar
      electrostatic influence on the hydrogen bond strength in bifluoride anion (FHF-).
      The present study shows that while low-barrier short hydrogen bonds can exist in
      the gas phase (the barrier for the hydrogen transfer in maleate anion is only 0.2
      kcal/mol at the QCISD(T)/6-311+G//QCISD/6-31+G level), whether they can also be
      strong in condensed media or not depends on how their interactions with their
      immediate environment affect their strength.

PMID- 11459495
TI  - Carbon-to-carbon identity proton transfer from allene, ketene, ketenimine, and
      thioketene to their respective conjugate anions in the gas phase. An ab initio
      study.
AB  - Gas-phase acidities of CH2=C=X (X = CH2, NH, O, and S) and barriers for the
      identity proton transfers (X=C=CH2 + HC triple bond C-X- right harpoon over left
      harpoon -X-C triple bond CH + CH2=C=X) as well as geometries and charge
      distributions of CH2=C=X, HC triple bond C-X- and the transition states of the
      proton transfer were determined by ab initio methods at the MP2/6
      311+G(d,p)//MP2/6-311+G(d,p) and B3LYP/6-311+G(d,p) levels of theory. The
      acidities were also calculated at the CCSD(T)/6-311+G(2df,p) level. A major
      objective of this study was to examine how the enhanced unsaturation of CH2=C=X
      compared to that of CH3CH=X may affect acidities, transition state imbalances,
      and intrinsic barriers of the identity proton transfer. The results show that the
      acidities are all higher while the barriers are lower than for the corresponding
      CH3CH=X series. The transition states are all imbalanced but less so than for the
      reactions of CH3CH=X.

PMID- 11459496
TI  - Strong supramolecular-based magnetic exchange in pi-stacked radicals. Structure
      and magnetism of a hydrogen-bonded verdazyl radical:hydroquinone molecular solid.
AB  - The X-ray crystal structure and magnetic properties of a molecular crystal
      consisting of 1,5-dimethyl-3-(2-pyridyl)-6-oxoverdazyl radical and hydroquinone
      (pyvd:hq) are presented. The structure contains a two-dimensional network of
      hydrogen bonds involving the hydroquinones and the pyridine ring of the pyvd
      radical. The radicals adopt an unusual head-over-tail (antiparallel) pi-stacked
      array perpendicular to the hydrogen-bonded planes. The variable-temperature
      magnetic susceptibility data can be modeled using a one-dimensional
      antiferromagnetic chain model, with J = -58 cm(-1). The strength of the magnetic
      coupling is very unusual because there are no close intermolecular radical
      radical contacts to provide conventional pathways for magnetic interactions. A
      pathway for coupling is proposed involving the mediation of magnetic exchange
      interactions between radical centers by the pyridine rings. Density functional
      calculations on the pyvd radical, as well as aggregates thereof based on the X
      ray structure, have been employed in attempts to understand the possible
      mechanisms by which the strong magnetic interactions are achieved.

PMID- 11459497
TI  - Electrodeposition of ordered Bi2Te3 nanowire arrays.

PMID- 11459499
TI  - Key process in palladium-catalyzed asymmetric transformation of propargyl
      electrophiles. Racemization of optically active eta1-allenylpalladium(II).

PMID- 11459498
TI  - A catalytic asymmetric Wagner-Meerwein shift.

PMID- 11459500
TI  - 1,1,3,3-tetramethylindan-2-selone-benzyne adduct: an isolable 2H-benzoselenete.

PMID- 11459501
TI  - High-sensitivity 2H NMR in solids by 1H detection.

PMID- 11459502
TI  - Effects of halide ligands and protic additives on enantioselectivity and
      reactivity in rhodium-catalyzed asymmetric ring-opening reactions.

PMID- 11459504
TI  - The first epoxidations of 1-amidoallenes. A general entry to nitrogen-substituted
      oxyallyl cations in highly stereoselective [4 +3] cycloadditions.

PMID- 11459503
TI  - Intrinsic fluorescence and quenching effects in photoactivated reactively
      sputtered silver oxide layers.

PMID- 11459505
TI  - Electrodeposition of epitaxial Cu(111) thin films on Au(111) using defect
      mediated growth.

PMID- 11459506
TI  - A ribozyme exclusively aminoacylates the 3'-hydroxyl group of the tRNA terminal
      adenosine.

PMID- 11459507
TI  - Efficient Lewis acid-catalyzed stereocontrolled radical polymerization of
      acrylamides.

PMID- 11459508
TI  - The asymmetric [3 + 2] cycloaddition reaction of chiral alkenyl Fischer carbene
      complexes with imines: synthesis of optically pure 2,5-disubstituted-3
      pyrrolidinones.

PMID- 11459509
TI  - Theoretical study of the regiochemistry-determining step of the Pauson-Khand
      reaction.

PMID- 11459510
TI  - Charge transfer spectroscopy in low-spin d6 pentacyano and pentaammine complexes.

PMID- 11459511
TI  - Oxygenation of nitrogen-coordinated palladium(0): synthetic, structural, and
      mechanistic studies and implications for aerobic oxidation catalysis.

PMID- 11459512
TI  - meso-aryl-substituted expanded porphyrins.

PMID- 11459513
TI  - A well-resolved ice-like (H2O)8 cluster in an organic supramolecular complex.

PMID- 11459514
TI  - A synthetically useful, self-assembling MMO mimic system for catalytic alkene
      epoxidation with aqueous H2O2.

PMID- 11459516
TI  - The use of percentage change from baseline as an outcome in a controlled trial is
      statistically inefficient: a simulation study.
AB  - BACKGROUND: Many randomized trials involve measuring a continuous outcome - such
      as pain, body weight or blood pressure - at baseline and after treatment. In this
      paper, I compare four possibilities for how such trials can be analyzed: post
      treatment; change between baseline and post-treatment; percentage change between
      baseline and post-treatment and analysis of covariance (ANCOVA) with baseline
      score as a covariate. The statistical power of each method was determined for a
      hypothetical randomized trial under a range of correlations between baseline and
      post-treatment scores. RESULTS: ANCOVA has the highest statistical power. Change
      from baseline has acceptable power when correlation between baseline and post
      treatment scores is high;when correlation is low, analyzing only post-treatment
      scores has reasonable power. Percentage change from baseline has the lowest
      statistical power and was highly sensitive to changes in variance. Theoretical
      considerations suggest that percentage change from baseline will also fail to
      protect from bias in the case of baseline imbalance and will lead to an excess of
      trials with non-normally distributed outcome data. CONCLUSIONS: Percentage change
      from baseline should not be used in statistical analysis. Trialists wishing to
      report this statistic should use another method, such as ANCOVA, and convert the
      results to a percentage change by using mean baseline scores.

PMID- 11459517
TI  - Color transitions in coral's fluorescent proteins by site-directed mutagenesis.
AB  - BACKGROUND: Green Fluorescent Protein (GFP) cloned from jellyfish Aequorea
      victoria and its homologs from corals Anthozoa have a great practical
      significance as in vivo markers of gene expression. Also, they are an interesting
      puzzle of protein science due to an unusual mechanism of chromophore formation
      and diversity of fluorescent colors. Fluorescent proteins can be subdivided into
      cyan (approximately 485 nm), green (approximately 505 nm), yellow (approximately
      540 nm), and red (>580 nm) emitters. RESULTS: Here we applied site-directed
      mutagenesis in order to investigate the structural background of color variety
      and possibility of shifting between different types of fluorescence. First, a
      blue-shifted mutant of cyan amFP486 was generated. Second, it was established
      that cyan and green emitters can be modified so as to produce an intermediate
      spectrum of fluorescence. Third, the relationship between green and yellow
      fluorescence was inspected on closely homologous green zFP506 and yellow zFP538
      proteins. The following transitions of colors were performed: yellow to green;
      yellow to dual color (green and yellow); and green to yellow. Fourth, we
      generated a mutant of cyan emitter dsFP483 that demonstrated dual color (cyan and
      red) fluorescence. CONCLUSIONS: Several amino acid substitutions were found to
      strongly affect fluorescence maxima. Some positions primarily found by sequence
      comparison were proved to be crucial for fluorescence of particular color. These
      results are the first step towards predicting the color of natural GFP-like
      proteins corresponding to newly identified cDNAs from corals.

PMID- 11459518
TI  - Pathological apoptosis by xanthurenic acid, a tryptophan metabolite: activation
      of cell caspases but not cytoskeleton breakdown.
AB  - BACKGROUND: A family of aspartate-specific cysteinyl proteases, named caspases,
      mediates programmed cell death, apoptosis. In this function, caspases are
      important for physiological processes such as development and maintenance of
      organ homeostasis. Caspases are, however, also engaged in aging and disease
      development. The factors inducing age-related caspase activation are not known.
      Xanthurenic acid, a product of tryptophan degradation, is present in blood and
      urine, and accumulates in organs with aging. RESULTS: Here, we report triggering
      of apoptotic key events by xanthurenic acid in vascular smooth muscle and retinal
      pigment epithelium cells. Upon exposure of these cells to xanthurenic acid a
      degradation of ICAD/DFF45, poly(ADP-ribose) polymerase, and gelsolin was
      observed, giving a pattern of protein cleavage characteristic for caspase-3
      activity. Active caspase-3, -8 and caspase-9 were detected by Western blot
      analysis and immunofluorescence. In the presence of xanthurenic acid the amino
      terminal fragment of gelsolin bound to the cytoskeleton, but did not lead to the
      usually observed cytoskeleton breakdown. Xanthurenic acid also caused
      mitochondrial migration, cytochrome C release, and destruction of mitochondria
      and nuclei. CONCLUSIONS: These results indicate that xanthurenic acid is a
      previously not recognized endogenous cell death factor. Its accumulation in cells
      may lead to accelerated caspase activation related to aging and disease
      development.

PMID- 11459519
TI  - [From self management to clinical governance].

PMID- 11459520
TI  - [Prevalence of orthostatic hypotension in elderly hypertensive patients in
      primary care].
AB  - OBJECTIVE: To find the prevalence of orthostatic hypotension (OH) and associated
      factors in elderly hypertensive patients in a primary care setting. DESIGN:
      Descriptive cross-sectional study. SETTING: La Marina Health Centre (an urban
      centre in Santander). PATIENTS: A random sample of 295 patients aged 65 years or
      older regularly assisted from hypertension. MEASUREMENTS AND MAIN RESULTS:
      Measurements of sitting and standing blood pressure were obtained. Orthostatic
      hypotension was defined as 20 mmHg or greater decrease in systolic or 10 mmHg or
      greater decrease in diastolic blood pressure after 1-minute or 5-minute standing.
      Associated diseases, symptoms upon standing, medication use, habits and other
      clinical assessments were also recorded. The prevalence of OH was 14.6%. The
      prevalence of systolic OH after 1-minute (OH-S1) and after 5-minute (OH-S5)
      standing was 5.8% in both, and the diastolic OH was 5.1% after 1-minute (OH-D1)
      and 4.1% after 5-minute (OH-D5) standing. By logistic regression analysis,
      association between higher level of systolic blood pressure and global OH was
      found, also with the presence of orthostatic intolerance symptoms (although only
      25.6% of the patients with OH showed symptoms) and smoking. Beta-blockers and
      calcium channel blockers (different from dihydropyridines) use was associated
      with OH after 1-minute standing and smoking with OH after 5-minute standing.
      CONCLUSIONS: The detected prevalence is high and justifies the case finding of OH
      in elderly hypertensive patients in primary care. The symptoms of orthostatic
      intolerance are correlated with OH, but only 1 out of 4 patients showed symptoms.
      Smoking could be related with OH, so beta-blockers and calcium channel blockers
      (different from dihydropyridines) use.

PMID- 11459521
TI  - [Cognitive structure of family doctors in training concerning the doctor-patient
      relationship].
AB  - OBJECTIVES: To find and compare thought structures of family doctors in training
      concerning the doctor-patient relationship. DESIGN: Qualitative and descriptive.
      SETTING: Primary care. PARTICIPANTS: 10 first-year residents selected through
      intentional sampling. MEASUREMENTS: Piaget interview modified by Pinies evaluated
      with the propositional analysis technique of concepts and conceptual maps. Five
      thematic areas concerning doctor-patient relationship were defined: importance
      and repercussions, characteristics and requisites, model of relationship, patient
      behaviour and doctor's behaviour. RESULTS: The concepts were not sufficiently
      elaborated. The importance of the doctor-patient relationship was recognised, but
      not all its repercussions. Its most oft cited desirable requisite was patient
      confidence. Those interviewed opted for a relationship in which the patient is
      passive, although they were aware of the danger of leading questions. The
      personality of the patient was the most commonly cited determinant of his/her
      behaviour, but other determinants were mentioned, such as beliefs and
      expectations. The decision to go for a consultation was not seen just as a
      product of the symptoms. Denial was the most widely recognised defence mechanism.
      The role of the doctor's feelings was indicated, but not about how to neutralise
      them. Training was not emphasised, either. CONCLUSIONS: There was insufficient
      appreciation of the practical importance of the doctor-patient relationship. A
      directive model of relationship was most common, lacking any biopsychosocial
      orientation. Training in this area, even though its need is not perceived, should
      be prioritised. The kind of knowledge underlying doctors' cognitive structure and
      its role in their behaviour should be investigated.

PMID- 11459522
TI  - [Health-related quality of life of elderly patients in primary care].
AB  - OBJECTIVES: To study the quality of life of the consultant elderly people and the
      associated factors to them. DESIGN: A transversal and observational study.
      SETTING: Primary care. An urban health center. PARTICIPANTS: Patients over 64
      years without any physical or psiquical limitation that disturb the communication
      between patient and doctor, that ask for a consultation. Election of a necessary
      sample trough consecutive sampling, to precision of 0,05 points and 95% CI.
      OPERATIONS: The patients filled out the valid version to Spanish of the
      Nottinghan Health Profile. The social demographics and the morbility variables
      were taken through clinical histories or in other case, through the patients
      interviews. MEASUREMENTS AND MAIN RESULTS: The questionnaire was answered for 386
      patients with a global mid punctuation of 9166 points (25,5% of deterioration;
      95% CI, 23,8-27,1%), being the deterioration in each one of following sizes:
      <<energy>> (22%; 95% CI, 25,3-18,7%); <<pain>> (22,5%; 95% CI, 24,9-20,1%);
      <<sleep>> (31,7%; 95% CI, 34,8-28,6%), <<social isolation>> (16,5%; 95% CI, 18,9
      14%); <<emotional state>> (27,9%; 95% CI, 30,5-25,8%) and <<mobility>> (28,3%;
      95% CI, 30,7-25,9%). It was presented with a high level of deterioration and with
      differences statistically significant, women (28,7% versus 19,0%; p < 0,001),
      except in <<energy>> sphere, patients with elevated age (23,1%, 21,1%, 24,4%,
      30,5% y 35,9% in 65-69, 70-74, 75-79, 80-84 and > 84 years old respectively; p <
      0,001), except in <<pain>> and <<sleep>> sphere), those who lived alone or
      without partner, those who were included in the house attention program 42,8%
      frente a 23,3%; p < 0,001), those who had a major number of chronic disease and
      those who took a great number of drugs. CONCLUSION: There are an important
      deterioration in the quality of life of our elderly people, associated to
      different social demography factors and morbidity. The assessment of the quality
      of life should be an habitual tool in our clinical practice.

PMID- 11459523
TI  - [Validation of the OMRON BF 300 monitor for measuring body fat by bioelectric
      impedance].
AB  - OBJECTIVES: To assess the accuracy of the OMRON BF 300 body fat monitor using
      bioelectric impedance and to validate its measurement of body fat percentage
      (BF%) against the Siri equation. DESIGN: Cross-sectional descriptive study.
      SETTING: Primary care. Coronel de Palma and San Fernando Health Centres,
      Mostoles. PARTICIPANTS: 88 people took part in the assessment of the accuracy of
      the monitor, and 91 in the validation. MEASUREMENTS AND MAIN RESULTS: The BF%
      were recorded in triplicate, with the mean being the figure noted. Precision was
      evaluated through the intra-class correlation coefficient (ICC) and the
      coefficient of variation (CV); validity, through technical error, the ICC and the
      Bland-Altman method. In the Siri equation, body density was calculated through
      the Durnin-Womersley equation. Precision: ICC was 0.999 and CV 0.4 +/- 0.03.
      VALIDATION: the difference between the BF% monitor (26.6 +/- 9.1%) and the Siri
      equation (27.8 +/- 8.2%) was -1.27% (p < 0.01; 95% CI -1.97 to -0.57); the
      technical error of the monitor was 2.2% and of the ICC 0.956 (95% CI, 0.9335
      0.9710). Thus, 80.2% of the monitor-equation differences were below 5%, with a
      concordance interval under the Bland-Altman method of +5.45 to -7.99%.
      CONCLUSIONS: The OMRON BF 300 monitor satisfies the precision criteria (ICC >
      0.95 and low CV) and validation (excellent technical error, ICC > 0.75 and
      clinically acceptable differences) and is a valid alternative to cutaneous folds
      as a method of assessing nutrition of the patient.

PMID- 11459524
TI  - [What is the best way to recruit patients for primary care programs of children's
      oral health?].
AB  - OBJECTIVE: To analyse the results obtained by two systems of recruiting patients
      in terms of: number of patients recruited, number of consultations requested, and
      number of half-yearly check-ups performed. DESIGN: Retrospective and
      observational. SETTING: Primary care. PATIENTS: 1868 school-children from 6 to 14
      in the Burela Health Area (Lugo). MAIN RESULTS: The system based on the health
      centre recruited 616 children and led to 759 requests for consultation; whereas
      the system based on the school recruited 1252 children and 507 requests (123% vs
      40%; p < 0.05). 23% of the school-children attended their half-yearly check-up
      under the first system, while 21% did so under the second. CONCLUSIONS: Check-ups
      of children at the health centre in their parents' presence seems to answer
      better the objective of introducing the bucco-dental health programme into the
      Health Area's child population.

PMID- 11459525
TI  - [Using the subcutaneous approach for symptoms control in a health center].
AB  - OBJECTIVE: To describe the use of the subcutaneous tract for symptoms control in
      patients those are in phase of palliative treatment of their illness. DESIGN:
      Observational study. SETTING: Primary care. PATIENTS: Patients seen in a health
      center, in phase of palliative treatment of their illness, that needed for
      symptoms control the subcutaneous administration of drugs. RESULTS: Most of the
      patients were in terminal phase (19), the fundamental cause (17 cases) that
      justified the use of the subcutaneous tract was the difficulty to take drugs by
      oral tract in the last days of life, attention on death throes. The infusion
      continuous through injector type travenol, at an infusion speed of 2 ml/h, it was
      the most common way of drug administration (19 patients). The drugs and initial
      average dose most used were: morphine 19 patients dose 100 mg/24 h, hyoscine
      butylbromide (Buscapina), 13 patients, 60 mg/24 h, haloperidol 12 patients, 4
      mg/24 h. The patients death was the main cause that justified the retirement of
      the continuous infusion (17 people sick), happening in its own home. Symptoms
      control was good or very good in the most of patients (14). CONCLUSIONS: The
      experience on using the subcutaneous tract for symptoms control in our health
      center is positive, being the fundamental cause for its use symptoms control in
      the last days of the patients life. The continuous subcutaneous infusion should
      be used in primary attention, as an usual technique for the symptoms control in
      patients that are in phase of palliative treatment of their illness.

PMID- 11459526
TI  - [Mad cow disease: absence of evidence is not evidence of absence].

PMID- 11459527
TI  - [Watchwords for type-2 diabetes prevention in primary health care. The dilemma of
      the pre-diabetic status].

PMID- 11459528
TI  - [Health questionnaire: concept and methodology].

PMID- 11459529
TI  - [Assessment of the taste of three paracetamol drop preparations].

PMID- 11459530
TI  - [Minor traumas].

PMID- 11459531
TI  - [Allergic reaction to the excipient of a generic drug].

PMID- 11459532
TI  - [Hypersensitivity to lamotrigine].

PMID- 11459534
TI  - [Acute ICU syndrome. Contributing factors and attitude of the nursing staff].
AB  - It is not uncommon for patients in intensive care units (ICUs) to suddenly and
      unexpectedly present what is known as acute ICU syndrome. This syndrome appears
      independently of the patient's situation and diagnosis. The aim of the present
      study was to determine the incidence of this nursing diagnosis in our department,
      to identify the possible environmental factors that could contribute to its
      appearance and to evaluate nursing interventions to resolve this syndrome in the
      ICU.Data were collected from a register of 62 items containing information on the
      health status of the patient on presenting the syndrome (vital signs, laboratory
      investigations, etc.), data on the environment, drugs used and other factors that
      could, a priori, play a role. The statistical analysis was performed using the
      SPSS program. This prospective study was carried out in a general ICU with ten
      beds: six beds in an open ward and four individual rooms. Two hundred forty-three
      patients were admitted during the 6-month study period. The incidence of ICU
      syndrome was 8.1 % (20 cases). Factors influencing its appearance were the timing
      of the shifts, the temperature, and whether patients were in individual rooms or
      open wards. The frequency of the syndrome was much higher in open wards and in
      the afternoon (from 15:00 to 22:00). In conclusion, the attitude of the nursing
      staff should be alert to identify the syndrome early and initiate appropriate
      measures, such as orienting the patient in time and space, achieving an
      appropriate temperature, using relaxation techniques, facilitating access to the
      family, etc., since in 35 % of cases these measures are sufficient to stabilize
      and/or resolve the problem, without the need of drugs.

PMID- 11459535
TI  - [Nursing care in the maintenance of potential donors in brain death].
AB  - The care provided by nurses to potential organ donors is essential to ensure the
      optimal utilization of transplant organs. With the aim of providing a reasoned
      description of such care, this article outlines the physiopathological changes
      produced in donors after brain death and identifies the nursing care required by
      these changes until the donor is taken to the operating room. The method used was
      a literature review. This study is structured according to the various
      physiological changes in the following sections: nursing care in the maintenance
      of (i) cardiovascular function, (ii) respiratory function, (ii) thermoregulation,
      (iv) hydroelectrolytic balance and endocrine-metabolic function, (v) renal
      function, (vi) corneas, (vii) prevention of infection, and (viii) other nursing
      care. The aim of all nursing care acts is to maintain the donor in optimum
      conditions in order to conserve the functioning of the maximum number of organs
      and thus ensure their successful transplantation. Finally, Annex I of the Royal
      Decree of December 30, 1999 is reproduced. This decree presents the protocols for
      the diagnosis and certification of death for organ extraction from donors in
      irreversible coma.

PMID- 11459536
TI  - [Weaning from mechanical ventilation. The aim of nursing research].
AB  - Management of patients difficult to wean from the ventilator is a practical
      challenge in which professional nurses are deeply involved.The clinical research
      applied over the last years has tried to describe the characteristics of weaning
      phenomenon and the associated factors, to find predictive outcomes to guide
      clinical decisions, to search new strategies to conduct the protocols and to
      identify the most effective modes of weaning. In this paper a critical review of
      the current knowledge from a nursing perspective is done. The weaning conceptual
      model proposed by the American Association of Critical Care Nurses (AACN) group
      has been used as a theoretical framework.

PMID- 11459537
TI  - [The intraosseal route. When the veins have disappeared].
AB  - The aim of this study was to demonstrate the usefulness of the intraosseal route
      in providing emergency vascular access, especially in children, when vascular
      access through peripheral or central routes is difficult or impossible. A
      literature review revealed that the intraosseal route provides rapid, easy and
      effective access to the vascular system, especially in children under the age of
      6 years. This route is indicated when, in emergencies, peripheral or central
      cannulation is too slow and the child's life is at risk. The most appropriate
      sites of insertion are the proximal or distal segments of the tibia and the
      distal segment of the femur. The administration of fluids, electrolytes and drugs
      through the intraosseal route is similar to that through the venous route.
      Complications are rare, the most serious being compartmental syndrome. In
      addition to providing an alternative route for the infusion of drugs and other
      substances into the bloodstream, the intraosseal route also provides access to
      the vascular system when samples for laboratory investigations are required. In
      conclusion, the intraosseal route provides rapid, safe and easy access to the
      vascular system. Complications are infrequent and there are few
      contraindications.

PMID- 11459544
TI  - [Study of the health education process in liver transplant recipients].
AB  - We present the results of a study carried out in Bellvitge University Hospital in
      Barcelona (Spain) in patients who underwent orthotopic liver transplantation and
      who are the subject of a health education program. Throughout the years, the
      structure of this program has undergone several changes. Initially, only verbal
      information supplied by a nurse on the knowledge required for patient self-care
      was envisaged. Through continuous evaluation, different forms of written and
      audiovisual information on patient self-care were introduced. The aim of this
      study was to evaluate patient knowledge on self-care by comparing compliance with
      recommendations at discharge among the patients who received verbal information
      only with that among patients who received verbal as well as written and/or
      audiovisual information. The study population comprised 434 patients who
      underwent liver transplantation from February 1984 to December 31, 1998. A
      retrospective cohort study was designed with two groups of patients. The first
      group was composed by 117 patients who received verbal, written and audiovisual
      information. The second group comprised 107 patients who received verbal
      information only. Data collection was through a telephone survey. Telephone
      interview was possible with only 98 patients in the first group and 60 in the
      second.In the overall evaluation of health education level, the score obtained by
      the first group was 8.3 (SD = 2.2) and that obtained by the second group was 6.8
      (SD = 1.8). The possible score was between 0 and 11. The differences between
      groups were statistically significant (p < 0.001). In general, patients who
      received verbal information only showed lower compliance with recommendations at
      discharge than those also received written and/or audiovisual information.

PMID- 11459545
TI  - [Drug administration through enteral feeding catheters].
AB  - Because of easiness and accessibility, the oral route of administration is
      usually the route of choice for medication delivery, as long as the oral drug
      form is available and the patients' circumstances allow it.In patients admitted
      to the intensive care unit this route is frequently altered. This provokes
      difficulties in swallowing and consequently an enteral feeding catheter must be
      inserted to supply the patient's nutritional requirements. This catheter is also
      used for the drug administration, which necessitates opening capsules or crushing
      pills before dilution. When added to drug-nutrient interactions, this process
      alters the drug's properties and modifies its pharmacokinetic profile, its
      pharmacological effect and the intensity of side effects. It can also provoke
      catheter obstruction. The aim of this study was to establish guidelines for drug
      administration through enteral feeding catheters. We provide a thorough review of
      the literature, describe oral drug forms, present a protocol for correct drug
      administration and provide a guide to the most commonly used drugs in our unit.
      For each of these drugs we include recommendations on administration and possible
      alternatives.

PMID- 11459546
TI  - [Bronchoalveolar lavage technique in patients with alveolar proteinosis].
AB  - Bronchoalveolar Lavage (BAL) was first described more than fifteen years ago; it
      is still the treatment of choice in Alveolar Proteinosis. Despite several
      clinical therapeutic trials, for new therapeutics none of them has achieved the
      results of Bronchoalveolar Lavage. It has been proved that, not only are they
      ineffective, but they can also have dangerous consequences. Alveolar proteinosis
      is a rare lung illness that implies the patient's hypoxia and progressive
      incapacity, being clinical dyspnea its most frequent characteristic. The BAL.
      with sodium chloride by filling and emptying the lungs allows to wash the
      fosfolipid material. That its on the alveoli giving the patient a great improve
      in short space of time. The aim of our work is to describe the technique used in
      Bronchoalveolar Lavage as well as the changes that have taken place since the
      beginning of its practice in our Critical Care Unit for the last fifteen years
      and so the nursing work that it is on this technic. This procedure needs to be
      made on a UCI for the need of mechanical ventilation. The time of instance on UCI
      is 24 h. In our experience we are able to make the BAL. in both lungs in the same
      session, there are no important complications and there is no need of
      readmission. We conclude that there is evidence that these treatment is
      effective.

PMID- 11459547
TI  - [Continuing education and self-evaluation. A review of the care for patients with
      disorders of the skin].

PMID- 11459562
TI  - [Living donor liver transplantation in adults. Initial results].
AB  - AIM: To analyze the preliminary results of the implementation of a living donor
      liver transplantation program. PATIENTS AND METHOD: Between March and September
      2000 we performed 7 living donor liver transplantations using the right hepatic
      lobe. The donors were 5 men and 2 women with a mean age of 39.3 11.5 years. Three
      donors were genetically related (daughter, mother, son). The mean relative liver
      volume transplanted was 58.8 2.5%. The mean age of the recipients was 50.4 16.5
      years. Six patients presented hepatitis C virus-induced cirrhosis and one
      presented familial amyloidotic polyneuropathy. RESULTS: Three complications
      occurred in the donors: 1 slight infection and 2 biliary fistulae. Graft function
      was adequate in all recipients and there were three acute rejections. Four
      biliary leakages occurred of which two required reoperation. None of the patients
      developed vascular thrombosis. Two recipients died, 53 and 72 days after the
      operation, with a correctly functioning graft. CONCLUSION: Living donor liver
      transplantation constitutes a necessary complement to the current cadaveric donor
      program to increase the number of patients who can benefit from this treatment,
      which may represent 10% of the activity of our center. The technical complexity
      of this procedure is much greater than that of cadaveric transplantation. The
      right hepatic lobe provides sufficient hepatic mass for most adult recipients.

PMID- 11459563
TI  - [Prognostic factors in gallbladder cancer].
AB  - BACKGROUND AND AIM: Carcinoma of the gallbladder is the most frequent biliary
      tract lesion but the 5-year survival is less than 5%. The aim of this study was
      to analyze the influence of several clinico-pathological variables on survival in
      a series of 226 carcinomas of the gallbladder. PATIENTS AND METHODS: The results
      were retrospectively analyzed and prognostic factors were identified by
      univariate statistical analysis and Cox regression model. All patients underwent
      surgery and in 67 of these (29.6%), surgery was potentially curative. In 63
      patients (27.9%) diagnosis was made when the resected gallbladder was studied for
      benign disease. Tumor node metastasis (TNM) stage was 0 in 7 patients (3.1%),
      stage I in 19 patients (8.4%), stage II in 21 patients (9.3%), stage III in 61
      patients (27%) and stage IV in 118 patients (52%). RESULTS: Overall 5-year
      survival was 17.3%. In the univariate analysis, significant variables were the
      presence of jaundice, weight loss, palpation of abdominal tumors at diagnosis,
      surgical technique, TNM stage and the three variables of this system (T: size, N:
      adenopathies; M: distant metastasis). In the multivariate analysis, the three
      variables of the TNM system and surgical technique were significantly associated
      with survival. CONCLUSIONS: The most important prognostic factor was TNM stage.
      Currently, radical cholecystectomy in stages II and III has become another
      important prognostic factor.

PMID- 11459564
TI  - [Endoscopic treatment of obstructive jaundice at a second level national health
      system hospital].
AB  - BACKGROUND AND AIMS: The difficulty of performing endoscopic retrograde
      cholangiopancreatography (ERCP) in our patients in the reference hospitals within
      a few days of diagnosis of obstructive jaundice led us to perform this technique
      in our center. We expected to perform a small number of ERCP annually. We
      analyzed the success rate of initial biliary drainage and the complications of
      this procedure. PATIENTS AND METHODS: We performed a retrospective study. From
      1997-1999 we carried out 240 ERCP. In 128 patients, 140 ERCP were performed for
      obstructive jaundice (58,3%). The final diagnosis was choledocholithiasis in 69
      patients (54%), tumors in 35 (27%), dilatation of the biliary tract without
      obstruction at cholangiography in 21 (17%) and benign stenosis of the biliary
      tract in 3 (2%). RESULTS: The mean procedure time for ERCP was 5.26 ( 2.8) days.
      Cholangiography was successfully performed in 117 patients (91.4%). Effective
      therapeutic endoscopy was performed in 111 patients (86.7%). Jaundice was
      resolved in 62 patients (90%) with choledocholithiasis, 55 (80%) by stone removal
      and in 7 (10%) by prosthesis. Resolution was also achieved in 25 (71.5%) tumors,
      mainly by prosthesis, and in 100% of patients with benign stenosis. In all
      patients with dilatation of the biliary tract without obstruction, biliary
      sphincterotomy was performed. Complications were found in 15 patients (11.7%) and
      two (1.56%) died. CONCLUSIONS: The majority of patients with obstructive jaundice
      can be satisfactorily treated in a center with our characteristics. However, in
      tumors, the figures for drainage were slightly lower than those reported in the
      medical literature.

PMID- 11459565
TI  - [Cost effectiveness study on the use of somatostatin for reduction of acute
      pancreatitis after ERCP].
AB  - OBJECTIVES: Recent studies show that intravenous injection of somatostatin before
      endoscopic retrograde cholangiopancreatography (ERCP) is associated with a
      significant reduction in the rate of post-ERCP acute pancreatitis. The lack of
      data in our environment led us to study the possible economic benefits of
      somatostatin administration, obtained through the reduction of costs due to post
      ERCP acute pancreatitis. MATERIAL AND METHODS: Theoretical study of the direct
      costs of post-ERCP acute pancreatitis using Markov's tree decisions. The costs of
      the group pre-treated with intravenous administration of 3 mg of somatostatin
      were compared with those of the control group. Post-ERCP rates of pancreatitis of
      10% were accepted in the control group and rates of 3% were accepted in the
      somatostatin group. The costs of the different types of pancreatitis were as
      follows: costs with and without complications and with surgical intervention were
      based on the diagnosis related group-weights applied by the Ministry of Health in
      the Contract-program of the Health Service of Navarre for 1999. A sensitivity
      analysis was carried out to determine the rate of post-ERCP pancreatitis from
      which an economic benefit would be obtained in the group pre-treated with
      somatostatin. RESULTS: Mean theoretical cost per procedure was 121,640 pesetas
      for the control group and 105,539 for the group pre-treated with somatostatin.
      Saving per patient was 13.26% (16,101 pesetas). The sensitivity analysis revealed
      that in the control group premedication produced an economic benefit starting
      from a pancreatitis rate of 4.2%. CONCLUSIONS: Independently of the clinical
      benefit signifying the reduction of post-ERCP pancreatitis, somatostatin
      administration led to a saving of 16,101 pesetas per patient. Accepting that the
      pancreatitis rate in the treated group was proportionately reduced, the
      sensitivity analysis showed that premedication produced an economic benefit
      starting from a pancreatitis rate of 4.2% in the control group.

PMID- 11459566
TI  - [Vulvar lymphedema: unusual manifestation of metastatic Crohn's disease].
AB  - Cutaneous-mucosal lesions constitute one of the most frequent extraintestinal
      manifestations of Crohn's disease and in some cases may be the first symptom of
      intestinal disease. We describe the case of a 45-year-old female patient who
      sought medical help for genital tumefaction of 20 years' evolution. For the
      previous 15 years, she had been experiencing digestive symptomatology attributed
      to irritable bowel syndrome. Two months before the consultation, and coinciding
      with aggravation of the condition, the patient had been diagnosed with colonic
      Crohn's disease. Skin biopsy of the labia minora revealed sarcoid granulomas. The
      results of microbiological studies (staining for microorganisms and cultures)
      were negative. A diagnosis of metastatic vulvar Crohn's disease was made and,
      treatment with metronidazole was started, which improved the genital edema after
      2 months. Genital lymphedema is an exceptionally rare manifestation of metastatic
      Crohn's disease that may appear several years before intestinal symptomatology
      develops. Treatment with metronidazole seems to be a good therapeutic option.

PMID- 11459567
TI  - [Abdominal actinomycosis simulating Crohn's disease].
AB  - Actinomycosis is a rare chronic infectious disease that usually develops
      abscesses and fistulas. It can also mimic other diseases such as cancer,
      inflammatory bowel diseases or diverticulitis. We present the case of a 67-year
      old woman with an unusual form of actinomycosis. Clinically, the disease
      simulated an inflammatory bowel disease. Computerized axial tomography,
      intestinal transit and colonoscopy were performed and the suspected 1 diagnosis
      continued to be inflammatory bowel disease. The definitive diagnosis was made
      after histopathological study of the surgical specimen. We highlight the
      diagnostic difficulty of this rare disease and the importance of prolonged
      antibiotic treatment.

PMID- 11459568
TI  - [Radiofrequency in the treatment of hepatocellular carcinoma].

PMID- 11459569
TI  - [New pathogenic concepts of pulmonary lesions in acute pancreatitis].

PMID- 11459570
TI  - [Isolated lesion of the gallbladder caused by closed abdominal injury].

PMID- 11459571
TI  - [Adenosquamous carcinoma of the colon].

PMID- 11459572
TI  - [Absence of inferior vena cava syndrome as a result of renal-splenic shunt].

PMID- 11459573
TI  - [Digestive lesions resulting from ingestion of caustic substances].

PMID- 11459574
TI  - [Opportunistic episodes in patients infected with the human immunodeficiency
      virus during the first 6 months of HAART].
AB  - BACKGROUND: We aimed at analysing the incidence and characteristics of
      opportunistic events (OE) within a few months after starting highly active
      antiretroviral therapy (HAART) in HIV infected patients. PATIENTS AND METHOD:
      Retrospective study of HIV infected outclinic patients attended in a HIV/AIDS
      reference hospital in Madrid, who initiated HAART during the second semester of
      1998, with a baseline CD4 cell count 250 x 10(6) cells/l. We recorded the
      incidence of OE within 6 months after beginning HAART and analysed virological
      and immunological parameters, sociodemographic variables and types of
      antiretroviral treatment. RESULTS: The study included 269 patients. Twenty-one
      (7.8%) OE were recorded. At the onset of HAART, the mean CD4 cell count in these
      21 patients was 137 (92) x 10(6)/land the median viral load was 24,043 cop/ml. At
      the time of OE diagnosis, these parameters were 218 (114) x 10(6)/l (p = 0.012)
      and < 500 cop/ml, respectively. OE were distributed as follows: herpes zoster, 9
      cases (43%), Pneumocystis carinii pneumonia, 5 cases (24%), Kaposi sarcoma,3
      cases (14%) and tuberculosis, cerebral toxoplasmosis, cytomegalovirus retinitis,
      and non-Hodgkin lymphoma, 1 case each. Overall, 78% of OE occurred within first 4
      months after beginning HAART. In addition, an OE was developed by 8% patients
      treated with NRTI and PI, 2% treated with NRTI and NNRTI, and 10% treated with
      NRTI,NNRTI and PI (p = 0.44). CONCLUSIONS: HIV-infected subjects with low CD4
      counts are prone to develop OE within the first few moths after beginning HAART.
      An inflammatory response to latent antigens due to the immune recovery might
      explain this fact.

PMID- 11459575
TI  - [Relationship between severity of essential arterial hypertension and the
      prevalence hyperuricemia].
AB  - BACKGROUND: Hyperuricemia has been associated with an increased risk of
      cardiovascular disease in hypertensive patients. However, the relation between
      serum urate and severity of hypertension has not been conclusively defined as
      yet. We aimed at finding out whether there exists an independent relationship
      between changes in the prevalence of hyperuricemia and severity of hypertension.
      PATIENTS AND METHOD: We studied 3 cohorts of patients aged 35 to 60 years with
      essential hypertension diagnosed at a university hospital in Madrid, Spain. The
      first cohort (before 1981) included 325 patients, the second (from 1981 to 1989)
      comprised 271 patients and the third cohort (from 1990 to 1999) included 545
      patients. Disease severity ranged from 1 to 6 according to blood pressure levels
      at diagnosis (WHO/ISH grades 1, 2 or 3 were assigned 1, 2 or 3 points,
      respectively) and target organ damage (left ventricular hypertrophy, hypertensive
      retinal vascular changes, and proteinuria above 300 mg/day; one point each).
      RESULTS: Mean serum urate concentrations in the 3 cohorts were 6.6, 5.8 and 5.5
      mg/dL, respectively (p < 0.05 for all comparisons). 39% of patients in the first
      cohort had a serum urate concentration > 7.0 mg/dL whereas only 18.1% patients in
      the third group showed hyperuricemia (difference: 20.9%; 95% CI, 10.1 to 32.3; p
      < 0.05). Severity of hypertension was higher in the first cohort (mean SD, 2.50
      1.31 points) than in the third group (1.96 1.06 points; p < 0.05), with the
      second cohort showing an intermediate severity (2.23 1.01 points). Serum urate
      levels were directly related to the severity of hypertension in the 3 groups (r =
      0.08, p < 0.05). In a multivariate analysis, after adjustment for confounding
      variables, serum urate had no significant association with severity of
      hypertension. However, target organ damage, systolic blood pressure and serum
      creatinine were all independent predictors of severity. CONCLUSIONS: Favourable
      changes in the severity of hypertension for a time period significantly correlate
      with decreases in hyperuricemia prevalence in the same period. On the other hand,
      hyperuricemia appears to be an indirect marker of hypertensive renal damage.

PMID- 11459576
TI  - [Predictive factors for inappropriate hospital stays in an internal medicine
      department].
AB  - BACKGROUND: We aimed to know which factors are associated with inappropriate
      stays in an internal medicine department. SUBJECTS AND METHOD: We included 1,046
      hospitalisations and evaluated the justification of the admission using the
      Appropriateness Evaluation Protocol. RESULTS: 176 (16.8%) stays were considered
      inappropriate. In a multiple regression model, variables defining an
      inappropriate stay were the number of days in hospital, diagnosis on admission
      and the weekly day. CONCLUSION: There are determining factors for inappropriate
      stays in an internal medicine department.

PMID- 11459577
TI  - [Hyperuricemia as a cardiovascular risk factor].

PMID- 11459578
TI  - [Fungal diseases].

PMID- 11459579
TI  - [Informed consent].

PMID- 11459580
TI  - [The virtual discussion: a new model of clinical session].

PMID- 11459581
TI  - [Evaluation and treatment of latent tuberculosis in the adult].

PMID- 11459582
TI  - [New antibiotic therapies for acute pharyngotonsillitis].

PMID- 11459583
TI  - [Evaluation of reactive strip for diagnosis of urinary infection in children and
      adults].

PMID- 11459585
TI  - [Stroke, age and dependency limitation].

PMID- 11459586
TI  - [Torsade de pointes and cardiorespiratory arrest induced by azithromycin in a
      patient with congenital long QT syndrome].

PMID- 11459588
TI  - Implicit processing of shadows.
AB  - Using synthetic objects, I investigate whether recognition performance is
      sensitive to different features of cast and attached shadows. Participants were
      required to recognise familiar objects presented to central vision while the
      presence, position and shape of cast and attached shadows were systematically
      manipulated. Costs in response time were found for naming objects in incongruent
      lighting and shadow conditions, that is, when the object was presented with a
      cast shadow that originated from a different object and when it was also non
      congruently illuminated (e.g. attached shadow indicating that the source of light
      was from the left, and cast shadow indicating that the source of light was from
      the right).

PMID- 11459589
TI  - Characterising temporal delay filters in biological motion detectors.
AB  - Motion detection requires the comparison of spatially and temporally displaced
      samples of the image. Here, we discuss the problems associated with measuring the
      delay between spatially displaced signals within biological motion detectors.
      Data are presented from direction-selective neurons in the nucleus of the optic
      tract of the wallaby, Macropus eugenii. Their motion responses depend on stimulus
      contrast and the adapted state of the cells. At low contrasts or in an adapted
      state, it appears that the input to the motion detectors is a temporally low
      passed version of the image. At high contrasts or in the unadapted state, the
      input signals appear to be temporally band-pass-filtered. Contrary to previous
      claims, we find that neither the response to stimulation with apparent motion nor
      measurements of temporal frequency response functions provide a direct estimate
      of the delay filter time constants. Instead, we find that both measures are also
      dependent on the temporal characteristics of prefiltering stages. A model is
      proposed to account for the responses of the neurons and their contrast
      dependence.

PMID- 11459590
TI  - Spatial aspects of object formation revealed by a new illusion, shine-through.
AB  - When a vernier stimulus is presented for a short time and followed by a grating
      comprising five straight lines, the vernier remains invisible but may bequeath
      its offset to the grating (feature inheritance). For more than seven grating
      elements, the vernier is rendered visible as a shine-through element. However,
      shine-through depends strongly on the spatio-temporal layout of the grating.
      Here, we show that spatially inhomogeneous gratings diminish shine-through and
      vernier discrimination. Even subtle deviations, in the range of a few minutes of
      arc, matter. However, longer presentation times of the vernier regenerate shine
      through. Feature inheritance and shine-through may become a useful tool in
      investigating such different topics as time course of information processing,
      feature binding, attention, and masking.

PMID- 11459591
TI  - Shine-through: temporal aspects.
AB  - If a vernier stimulus precedes a grating for a very short time, the vernier
      either remains invisible, but may bequeath some of its properties to the grating
      (feature inheritance), or might shine through keeping its features - depending on
      the number of grating elements [Herzog, M. H. & Koch, C., 2001. Seeing properties
      of an invisible element: feature inheritance and shine-through. Proceedings of
      the National Academy of Science USA 98, 4271-4275]. Feature inheritance and shine
      through represent two different states of feature binding [Herzog, M. H., Koch,
      C., & Fahle, M., Switching binding states. Visual Cognition (in press)], whereas
      shine-through depends in subtle ways on the spatial layout of the grating
      [Herzog, M. H., Fahle, M., & Koch, C., (2001). Spatial aspects of object
      formation revealed by a new illusion, shine-through Vision Research]. Here, we
      show that also temporal parameters of the grating influence shine-through. For
      example, a delayed presentation of certain grating elements can deteriorate
      performance dramatically.

PMID- 11459592
TI  - Two competing mechanisms underlying neon color spreading, visual phantoms and
      grating induction.
AB  - Neon color spreading is closely related to the photopic visual phantom illusion,
      since these two completion phenomena are characterized by in-phase lightness
      induction, and the only difference in the stimulus configuration is the
      difference in the inducer height. This idea was supported by the present study.
      Neon color spreading showed almost the same function of critical spatial
      frequency as photopic visual phantoms (Experiment 1), and the critical spatial
      frequency was constant as the inducer height was changed (Experiment 2). We also
      examined the relationship between neon color spreading and grating induction
      (characterized by counterphase lightness induction) in critical spatial frequency
      (Experiment 3) and in magnitudes of lightness induction (Experiment 4) as a
      function of the inducer height. The inducer height at which in-phase (neon color
      spreading) appearance gave way to counterphase (grating) induction was
      approximately 0.1 deg. These results suggest that neon color spreading shares a
      common neural mechanism with the photopic visual phantom illusion and that this
      mechanism is different from, and competes with, the mechanism of grating
      induction.

PMID- 11459593
TI  - Sensitive calibration and measurement procedures based on the amplification
      principle in motion perception.
AB  - We compare two types of sampled motion stimuli: ordinary periodic displays with
      modulation amplitude m(o=e) that translate 90 degrees between successive frames
      and amplifier sandwich displays. In sandwich displays, even-numbered frames are
      of one type, odd-numbered frames are of the same or different type, and (1) both
      types have the same period, (2) translate in a consistent direction 90 degrees
      between frames, and (3) even frames have modulation amplitude m(e), odd frames
      have modulation amplitude m(o). In both first-order motion (van Santen, J.P.H. &
      Sperling, G. (1984). Temporal covariance model of human motion perception.
      Journal of the Optical Society of America A, 1, 451-73) and second-order motion
      (Werkhoven, P., Sperling, G., & Chubb, C. (1993). Motion perception between
      dissimilar gratings: a single channel theory. Vision Research, 33, 463-85) the
      motion strength of amplifier sandwich displays is proportional to the product
      m(o)m(e) for a wide range of m(e). By setting m(e) to a large value, an amplifier
      sandwich stimulus with a very small value of m(o) can still produce visible
      motion. The amplification factor is the ratio of two threshold modulation
      amplitudes: ordinary circumflexm(o=e) over amplified circumflexm(o),
      circumflexm(o=e)/circumflexm(o). We find amplification factors of up to about 8x.
      Light adaptation and contrast gain control in early visual processing distort the
      representations of visual stimuli so that inputs to subsequent perceptual
      processes contain undesired distortion products or 'impurities'. Motion
      amplification is used to measure and thence to reduce these unwanted components
      in a stimulus to a small fraction of their threshold. Such stimuli are
      certifiably pure in the sense that the residual impurity is less than a specified
      value. Six applications are considered: (1) removing (first-order) luminance
      contamination from moving (second-order) texture gratings; (2) removing luminance
      contamination from moving chromatic gratings to produce pure isoluminant
      gratings; (3) removing distortion products in luminance-modulated (first-order)
      gratings - by iterative application, all significant distortion products can be
      removed; (4) removing second-order texture contamination from third-order motion
      displays; (5) removing feature bias from third-order motion displays; (6) and the
      same general principles are applied to texture-slant discrimination in which x,y
      spatial coordinates replace the x,t motion coordinates. In all applicable
      domains, the amplification principle provides a powerful assay method for the
      precise measurement of very weak stimuli, and thereby a means of producing visual
      displays of certifiable purity.

PMID- 11459594
TI  - Pursuit affects precision of perceived heading for small viewing apertures.
AB  - We investigated the interaction between extra-retinal rotation signals and
      retinal motion signals in heading perception during pursuit eye movement. For
      limited viewing aperture, the variability in perceived heading strongly depends
      on the pattern of motion directions. Heading towards a point outside the aperture
      generates nearly parallel aperture flow. This results in lower precision of
      perceived heading than heading that renders the radial pattern of flow visible.
      We ask if the precision is limited by the pattern of flow visible on the retina
      or that on the screen. During fixation, the two patterns are identical. They are
      decoupled during pursuit, since pursuit changes radial flow within the aperture
      on the screen into nearly parallel flow on the retina, and vice versa. The extra
      retinal signal is known to reduce systematic errors in the direction of pursuit,
      thus compensating for the rotational flow during pursuit. We now ask if the extra
      retinal signal also affects the precision of heading percepts. It might if at the
      spatial integration stage the rotational flow has been subtracted out already. A
      compensation beyond the integration stage, however, cannot undo the change in
      retinal motion directions so that an effect of pursuit on precision cannot be
      avoided. We measured the variable and systematic errors in perceived heading
      during fixation and pursuit for a frontal plane approach, while varying duration,
      dot lifetime and aperture size. We found precision is effected by pursuit as much
      as predicted from the pattern of retinal flow, while compensation is
      significantly greater than zero. This means that the interaction between the
      extra-retinal signal and visual motion signals takes place after spatial
      integration of local motion signals. Furthermore, compensation increased
      significantly with longer duration (0.5-3.0 s), but not with larger aperture size
      (10-50 degrees ). A larger aperture size did increase the eccentricity of
      perceived heading.

PMID- 11459595
TI  - Saccades to remembered targets exhibit enhanced orbital position effects in
      monkeys.
AB  - Remembered saccades of rhesus monkeys are markedly influenced by starting eye
      position. Altering the initial position systematically affects the direction or
      amplitude of the movements to a striking degree. In general, changes in the
      horizontal or vertical starting position primarily produce changes in the
      horizontal or vertical component, respectively, regardless of whether the target
      displacement occurs in the horizontal or vertical direction. For some monkeys, a
      similar pattern of initial position influence on movement direction can be seen
      in the curvature of visually guided saccades. Starting position also modulates
      the upward offset in fixation, which monkeys display in the dark.

PMID- 11459596
TI  - Saccades guided by somatosensory stimuli.
AB  - The accuracy of somatosensory saccades defined by proprioceptive cues with and
      without an additional tactile stimulus was investigated over a wide range of
      stimulus amplitudes in 16 normal subjects. The present results confirm that
      somatosensory saccades are less accurate and more variable than visual saccades.
      Accuracy was minimal for saccades directed to hand distances of 40-50 deg and
      increased for larger stimulus amplitudes. The additional application of a tactile
      cue on the fingertip was not found to influence the accuracy of somatosensory
      saccades significantly.

PMID- 11459597
TI  - A two-layer sparse coding model learns simple and complex cell receptive fields
      and topography from natural images.
AB  - The classical receptive fields of simple cells in the visual cortex have been
      shown to emerge from the statistical properties of natural images by forcing the
      cell responses to be maximally sparse, i.e. significantly activated only rarely.
      Here, we show that this single principle of sparseness can also lead to emergence
      of topography (columnar organization) and complex cell properties as well. These
      are obtained by maximizing the sparsenesses of locally pooled energies, which
      correspond to complex cell outputs. Thus, we obtain a highly parsimonious model
      of how these properties of the visual cortex are adapted to the characteristics
      of the natural input.

PMID- 11459599
TI  - Avoidance of radiation injuries from medical interventional procedures.
AB  - Interventional radiology (fluoroscopically-guided) techniques are being used by
      an increasing number of clinicians not adequately trained in radiation safety or
      radiobiology. Many of these interventionists are not aware of the potential for
      injury from these procedures or the simple methods for decreasing their
      incidence. Many patients are not being counselled on the radiation risks, nor
      followed up when radiation doses from difficult procedures may lead to injury.
      Some patients are suffering radiation-induced skin injuries and younger patients
      may face an increased risk of future cancer. Interventionists are having their
      practice limited or suffering injury, and are exposing their staff to high doses.
      In some interventional procedures, skin doses to patients approach those
      experienced in some cancer radiotherapy fractions. Radiation-induced skin
      injuries are occurring in patients due to the use of inappropriate equipment and,
      more often, poor operational technique. Injuries to physicians and staff
      performing interventional procedures have also been observed. Acute radiation
      doses (to patients) may cause erythema at 2 Gy, cataract at 2 Gy, permanent
      epilation at 7 Gy, and delayed skin necrosis at 12 Gy. Protracted (occupational)
      exposures to the eye may cause cataract at 4 Gy if the dose is received in less
      than 3 months, at 5.5 Gy if received over a period exceeding 3 months. Practical
      actions to control dose to the patient and to the staff are listed. The absorbed
      dose to the patient in the area of skin that receives the maximum dose is of
      priority concern. Each local clinical protocol should include, for each type of
      interventional procedure, a statement on the cumulative skin doses and skin sites
      associated with the various parts of the procedure. Interventionists should be
      trained to use information on skin dose and on practical techniques to control
      dose. Maximum cumulative absorbed doses that appear to approach or exceed 1 Gy
      (for procedures that may be repeated) or 3 Gy (for any procedure) should be
      recorded in the patient record, and there should be a patient follow-up procedure
      for such cases. Patients should be counselled if there is a significant risk of
      radiation-induced injury, and the patient's personal physician should be informed
      of the possibility of radiation effects. Training in radiological protection for
      patients and staff should be an integral part of the education for those using
      interventional techniques. All interventionists should audit and review the
      outcomes of their procedures for radiation injury. Risks and benefits, including
      radiation risks, should be taken into account when new interventional techniques
      are introduced.A concluding list of recommendations is given. Annexes list
      procedures, patient and staff doses, a sample local clinical protocol, dose
      quantities used, and a procurement checklist.

PMID- 11459612
TI  - Functional evaluation of peripheral nerve regeneration in the rat: walking track
      analysis.
AB  - The experimental model of choice for many peripheral nerve investigators is the
      rat. Walking track analysis is a useful tool in the evaluation of functional
      peripheral nerve recovery in the rat. This quantitative method of analyzing hind
      limbs performance by examining footprints, known as the sciatic function index
      (SFI), has been widely used to quantify functional recovery from sciatic nerve
      injury in a number of different injury models, although some limitations of the
      SFI has been questioned by several authors. This article is designed to offer the
      peripheral nerve investigator a noninvasive method to evaluate quantitatively the
      integrated motor recovery in experimental studies.

PMID- 11459613
TI  - Removal of ECG interference from the EEG recordings in small animals using
      independent component analysis.
AB  - In experiments involving small animals, the electroencephalogram (EEG) recorded
      during severe injury and accompanying resuscitation exhibit the strong presence
      of electrocardiogram (ECG). For improved quantitative EEG (qEEG) analysis, it is
      therefore imperative to remove ECG interference from EEG. In this paper, we
      validate the use of independent component analysis (ICA) to effectively suppress
      the interference of ECG from EEG recordings during normal activity, asphyxia and
      recovery following asphyxia. Two channels of EEG from five rats were recorded
      continuously for 2 h. Simultaneous recording of one channel ECG was also made.
      Epochs of 4 s and 1 min were selected from baseline, asphyxia and recovery (every
      10 min) and their independent components and power spectra were calculated. The
      improvement in normalized power spectrum of EEG obtained for all animals was
      7.71+/-3.63 db at the 3rd minute of recovery and dropped to 1.15+/-0.60 db at
      63rd minute. The application of ICA has been particularly useful when the power
      of EEG is low, such as that observed during early brain hypoxic-asphyxic injury.
      The method is also useful in situations where accurate indications of EEG signal
      power and frequency content are needed.

PMID- 11459614
TI  - Retrograde labeling of primary sensory neurons with fluorescent latex
      microspheres: a useful tool for long term tagging of neurons.
AB  - In this study we have used fluorescent microspheres to retrogradely label primary
      sensory neurons in dorsal root ganglia (DRGs). Following injection into
      peripheral nerves, the animals were allowed to survive up to 480 days. Simple
      profile count indicates that there is a substantial retention of the labeling
      still after at least 480 days, i.e. about two-thirds of a rat's life span.
      Moreover, the appearance of the labeling remains quite distinct. Using
      established markers for axon damage of DRG neurons, we could detect a slight and
      transient effect of the peripheral nerve injection on the gene expression
      pattern. It is concluded that fluorescent microspheres represents an attractive
      means of tagging neurons in experiments covering long time periods.

PMID- 11459615
TI  - Measurement of ataxic symptoms with a graphic tablet: standard values in controls
      and validity in Multiple Sclerosis patients.
AB  - Aim of our study was to find a specific measure for the intensity of upper limb
      tremor and other ataxic symptoms in Multiple Sclerosis (MS) patients, and to
      establish standard values and test quality parameters. Three hundred and forty
      two consecutive patients with different symptoms in the upper limbs (upper motor
      neuron symptoms, cerebellar upper limb ataxia, and/or sensory deficits in the
      upper limbs) and 140 healthy controls took part in the study. All patients and
      controls had to trace over a 25 cm high figure '8' on a graphic tablet, to tap
      with the stylus on the tablet and to perform the nine-hole-peg test (9HPT).
      Patients were additionally examined using clinical standard scales to classify
      motor dysfunctions of the upper limbs. One hundred and eighty-nine patients and
      27 controls were tested twice to investigate the test reliability. Kinematic
      analysis of the tablet data was performed by kernel estimators, oscillatory
      activity by spectral analysis. Total power in the 2--10 Hz band was very specific
      for ataxia versus other motor symptoms. Tapping and 9HPT could well distinguish
      patients from controls, and patients with predominant motor neuron or cerebellar
      symptoms from patients with predominant sensory dysfunctions. Mean drawing error
      did not differ between motor and sensory dysfunctions. The test--retest
      reliability was similarly high for both spectral analysis and 9HPT.

PMID- 11459616
TI  - Extended dynamic clamp: controlling up to four neurons using a single desktop
      computer and interface.
AB  - The dynamic clamp protocol allows an experimenter to simulate the presence of
      membrane conductances in, and synaptic connections between, biological neurons.
      Existing protocols and commercial ADC/DAC boards provide ready control in and
      between < or =2 neurons. Control at >2 sites is desirable when studying neural
      circuits with serial or ring connectivity. Here, we describe how to extend
      dynamic clamp control to four neurons and their associated synaptic interactions,
      using a single IBM-compatible PC, an ADC/DAC interface with two analog outputs,
      and an additional demultiplexing circuit. A specific C++ program, DYNCLAMP4,
      implements these procedures in a Windows environment, allowing one to change
      parameters while the dynamic clamp is running. Computational efficiency is
      increased by varying the duration of the input-output cycle. The program
      simulates < or =8 Hodgkin-Huxley-type conductances and < or =18 (chemical and/or
      electrical) synapses in < or =4 neurons and runs at a minimum update rate of 5
      kHz on a 450 MHz CPU. (Increased speed is possible in a two-neuron version that
      does not need auxiliary circuitry). Using identified neurons of the crustacean
      stomatogastric ganglion, we illustrate on-line parameter modification and the
      construction of three-member synaptic rings.

PMID- 11459617
TI  - Lactate dehydrogenase release is facilitated by brief sonication of rat
      hippocampal slices and isolated retinas following acute neuronal damage.
AB  - Although useful for determining neuronal damage in cell cultures, the lactate
      dehydrogenase (LDH) assay is not suitable for acute brain preparations because
      LDH release is typically delayed relative to neuronal deterioration. The slow
      release suggests that LDH may remain trapped inside damaged cells until late in
      the degenerative process. To test this, we examined whether brief sonication
      facilitates LDH release from acutely damaged neurons. In rat isolated retinas and
      hippocampal slices, LDH release was minimal following acute administration of
      iodoacetate or kainate. However, these toxins promoted significant LDH release,
      when toxin exposure was followed by brief sonication. Increases in extracellular
      LDH correlated with changes in neuronal morphology. These findings suggest that
      sonication may facilitate the use of the LDH assay in acute brain preparations.

PMID- 11459618
TI  - Comparison of two independent aromatic hydroxylation assays in combination with
      intracerebral microdialysis to determine hydroxyl free radicals.
AB  - The phenylalanine- and salicylate assay were compared to investigate the
      production of hydroxyl free radicals. In vitro experiment: Phenylalanine (100
      micromol/l) or salicylic acid (100 micropmol/l) were incubated in a hydroxyl
      radical generating in vitro Fenton system with increasing concentrations (1.25-
      40 micromol/l) of equimolar hydrogen peroxide and ferrous ions. Both,
      phenylalanine and salicylic acid were able to trap hydroxyl radicals in a
      reliable way indicated by the linear relationship between the concentration of
      the Fenton reagents and either the phenylalanine derived products (ortho-, meta-,
      para-tyrosine) or the salicylic acid-derived products (2,3- and 2,5
      dihydroxybenzoic acid (DHBA)). In vivo experiment: Wistar rats were implanted
      with microdialysis probes and striatal perfusion with either 5 mmol/l
      phenylalanine or 5 mmol/l salicylic acid was performed. Addition of the
      dopaminergic neurotoxin 6-hydroxydopamine (100 micromol/l, flow rate 2
      microl/min, 60 min) to the perfusion fluid significantly increased the
      concentrations of ortho- and meta-tyrosine or 2,3-DHBA in comparison to control
      animals. All increases determined were rapidly reversible after changing back to
      pre-stimulation conditions. The results demonstrate that aromatic hydroxylation
      of phenylalanine or salicylic acid is a useful technique to investigate hydroxyl
      free radical formation in vitro and in vivo. Advantages and disadvantages of both
      methods are discussed.

PMID- 11459619
TI  - Diagnostic yield of the lactate stress test in respiratory chain disorders under
      absolute and relative workload.
AB  - Usually, the lactate stress test is carried under a constant, low workload
      maintained for 15 min, although there are indications that the lactate response
      to exercise is a function of the relative workload, and that a workload for only
      5 min does not decrease its sensitivity. Thus, this study compared the diagnostic
      yield of the lactate stress test when carried out under a constant workload of 30
      W (LSTA) and under a workload of 30% of maximum (LSTR), and when the workload was
      maintained for 5 and 15 min. In 16 patients with respiratory chain disorders, 12
      women, four men, aged 27--88 years, the LSTA and LSTR were carried out on 2
      different days, within 48 h. For both tests serum lactate was determined before,
      during and after a 15-min workload on a bicycle. Upper reference limits at rest,
      5, 10, 15 min after starting, and 15 min after finishing the exercise were 1.9,
      2.0, 2.0, 2.0, and 1.6 mmol/l for the LSTA, and 2.3, 3.0, 3.2, 3.4 and 2.7 mmol/l
      for the LSTR. The sensitivity was 88% for the LSTA and 63% for the LSTR. The
      specificity of the LSTA was 94%. The diagnostic yield of both tests was similar
      when the workload was maintained for 5 or 15 min. In conclusion, the LSTA should
      be preferred to the LSTR. Three lactate determinations during 15 min have no
      advantage over a single lactate determination after a 5 min workload of 30 W.

PMID- 11459620
TI  - The LTP Program: a data acquisition program for on-line analysis of long-term
      potentiation and other synaptic events.
AB  - The LTP Program is a stimulation, acquisition and on-line analysis program for
      studying long-term potentiation (LTP), long-term depression (LTD), and stimulus
      evoked synaptic responses in general. The program is freely available from the
      website: www.ltp-program.com. It is a 32-bit DOS program that runs on Windows
      3/95/98 computers having a Pico Technologies ADC-42, Axon Instruments' Digidata
      1200, or Scientific Solution's Labmaster acquisition board. The program records
      two channels of activity in extracellular, current- or voltage clamp modes. It
      acquires < or =1,000,000 samples per sweep, and has extracellular dual pathway
      stimulation and epoch-like intracellular stimulation. Basic protocols include
      slow alternating dual pathway stimulation. LTP is induced by single train, theta
      burst, or primed burst stimulation. LTD is induced using fast repetitive 1 pulse
      sweeps (< or =2 Hz). The program analyzes all stimulus-evoked synaptic responses
      in both acquisition channels. Analyzes include: slope, peak amplitude/latency,
      population spike amplitude/latency, average amplitude, duration, area, rise time,
      decay time, coastline, cell resistance and patch electrode series resistance.
      Sweeps can be averaged and digitally filtered. Trains can be analyzed by
      measuring the responses of all pulses relative to the baseline of the first
      pulse. Stimulus artifacts can be automatically removed for accurate determination
      of synaptic areas and peaks during a train.

PMID- 11459621
TI  - Visualization of rat pial microcirculation using the novel orthogonal polarized
      spectral (OPS) imaging after brain injury.
AB  - Recently, the novel optical system, orthogonal polarized spectral (OPS) imaging
      was developed to visualize microcirculation. Investigation of changes in
      microcirculation is essential for physiological, pathophysiological, and
      pharmacological studies. In the present study applicability of OPS imaging was
      assessed to study pial microcirculation in normal and traumatized rat brain. High
      quality images of rat pial microcirculation in normal and traumatized rats were
      generated with the OPS imaging, allowing to easily differentiate arterioles and
      venules with the dura remaining intact. In non-traumatized rats, mean vessel
      diameter of arterioles and venules of five different cortical regions was 19.1+/
      2.7 and 22.2+/-1.4 microm, respectively. In the early phase following focal
      cortical contusion vessel diameter was significantly decreased in arterioles by
      28% while diameter in venules was significantly increased by 27%. For technical
      reasons velocity in arterioles was not measurable. In venules, mean flow velocity
      of 0.68+/-0.08 mm/s was significantly decreased by 50% at 30 min after trauma.
      OPS imaging is an easy to use optical system allowing to generate high quality
      images and to reliably investigate pial microcirculation without having to remove
      the dura. This technique opens the possibility to perform longitudinal studies
      investigating changes in pial microcirculation.

PMID- 11459622
TI  - Fiber-optic monitoring coupled with confocal microscopy for imaging gene
      expression in vitro and in vivo.
AB  - Detection of fluorescent signals in living cells is a common and powerful
      technique used to monitor gene expression for multiple biomedical applications. A
      disadvantage of this approach in vivo, is the limited accessibility for long-term
      monitoring of the fluorescent signals within organs in living animals. Because of
      the multiple applications of gene expression monitoring through fluorescent
      signals, innovative methods for readout are required. We developed a strategy
      combining gene transfer, fiber-optic or endoscope monitoring, and confocal
      microscopy for the brain interstitial or cavitary endoscopic visualization of the
      efficacy of gene delivery and expression in vivo. The approach is also effective
      in vitro and can be applied to multiple organs in vivo. We show an example of the
      detection of green fluorescent protein (GFP)-emitted fluorescence following the
      administration of recombinant GFP-expressing adenovirus or implantation of rat C6
      glioblastoma cells infected with the recombinant GFP adenovirus into the rat
      hippocampus of chronically cannulated rats. The results show that fiber-optic
      monitoring coupled with confocal microscopy in gene transfer studies is a
      practical approach that results in a direct, efficient, rapid, and sensitive
      visualization of fluorescent signals in the brain. This allows for the continuous
      real-time in vitro or in vivo brain monitoring of gene expression, accurate
      anatomical localization, multiple experimental manipulations in the same subject
      or preparation, while no sacrifice of the animal is required to monitor the
      efficacy of gene transfer and/or expression.

PMID- 11459623
TI  - Rapid lesioning of large numbers of identified vertebrate neurons: applications
      in zebrafish.
AB  - Establishing a causal role between the activity of specific individual nerve
      cells and the behaviors they produce (or the neural computations they execute) is
      made difficult in vertebrate animals because of the large numbers of neurons
      involved. Traditional techniques for establishing causal roles, such as tract
      cutting and electrolytic lesions, are limited because they produce damage that
      affects a variety of different cell types, invariably intermingled, and often of
      uncertain identity. We propose here an alternative lesioning technique in which
      large numbers of neurons are lesioned, but the lesioned neurons are specifically
      identified by fluorescent labeling. We use the locomotor control system of the
      larval zebrafish to illustrate this approach. In this example, the technique
      involves injection of fluorescent dextrans into far-rostral spinal cord to label
      descending nerve fibers. Such injections appear to interrupt the descending nerve
      fibers, and therefore their accompanying locomotor control signals. This protocol
      is shown to produce significant behavioral deficits. Because the CNS of the
      larval zebrafish is transparent, the entire population of lesioned cells can be
      imaged in vivo and reconstructed using confocal microscopy. This large-scale
      lesioning technique is important, even in this relatively 'simple' vertebrate
      animal, because the ablation of smaller numbers of neurons, using more precise
      laser-ablation techniques, often fails to produce observable behavioral deficits.
      While this technique is most readily applied in simpler and transparent
      vertebrate animals, the approach is general in nature and might, in principle, be
      applied to any vertebrate nerve tract.

PMID- 11459624
TI  - Computer-assisted health impact assessment for intersectoral health policy.
AB  - Intersectoral health policy implies negotiations with politicians outside the
      health sector. Health politicians have a stronger position if they can quantify
      health impact. In this Dutch case-study we used a computer simulation approach to
      answer the following questions: Which anti-tobacco intervention has the largest
      health gain? Will a commuter cycling policy result in any substantial health
      gain? What is the relative health gain of promoting higher consumption of
      vegetables and fruit? We concluded that substantial health gain can be achieved
      if cigarette packet price were to increase by 2 Dutch guilders. A commitment of
      all general practitioners to implement a smoking cessation intervention will
      result in a similar health gain. Stimulating commuter cycling could be a
      promising example of intersectoral health policy. Interventions to promote higher
      vegetable and fruit consumption will result in a relatively small health gain.
      Pros and cons of simulation models to support intersectoral health policy are
      discussed.

PMID- 11459625
TI  - Prospects for tobacco control in Zimbabwe: a historical perspective.
AB  - Using a historical and political economy perspective, this paper explores the
      prospects for tobacco control in Zimbabwe, the world's sixth largest producer and
      third largest tobacco exporter. Tobacco production, which first began in the
      former Rhodesia in the early 1900s, is closely associated with colonial history
      and land occupation by white settlers. The Zimbabwe (formerly Rhodesia) Tobacco
      Association was formed in 1928 and soon became a powerful political force.
      Although land redistribution has always been a central issue, it was not
      adequately addressed after independence in 1980, largely due to the need for
      Zimbabwe to gain foreign currency and safeguard employment. However, by the mid
      1990s political pressures forced the government to confront the mainly white,
      commercial farmers with a new land acquisition policy, but intense national and
      international lobbying prevented its implementation. With advent of global
      economic changes, and following the start of a structural adjustment programme in
      1991, manufacturing began to decline and the government relied even more on the
      earnings from tobacco exports. Thus strengthening tobacco control policies has
      always had a low national and public health priority. Recent illegal occupation
      of predominantly white owned farms, under the guise of implementing the former
      land redistribution policy, was politically motivated as the government faced its
      first major challenge at the general elections in June 2000. It remains unclear
      whether this will lead to long term reductions in tobacco production, although
      future global declines in demand could weaken the tobacco lobby. However, since
      Zimbabwe is only a minor consumer of tobacco, a unique opportunity does exist to
      develop controls on domestic cigarette consumption. To achieve this the isolated
      ministry of health would need considerable support from international agencies,
      such as the World Health Organisation and World Bank.

PMID- 11459626
TI  - Symptom-based outcome measures for asthma: the use of discrete choice methods to
      assess patient preferences.
AB  - This paper reports on an application of discrete choice modelling to the
      measurement of patient preferences over asthma symptoms. A sample of patients
      with moderate to severe asthma was asked to choose between a series of pairs of
      scenarios characterised by different combinations of asthma symptoms. Their
      responses were analysed using a random effects ordered probit model. The results
      implied that patients weighted some symptoms more highly than others. Discrete
      choice modelling proved to be a useful approach for developing preference based
      outcome measures, although the results show how, in contexts where preferences
      over health care outcomes based on symptoms or some measure of health status are
      involved, a conventional linear additive model may not always be suitable.

PMID- 11459627
TI  - Equity in health in unequal societies: meeting health needs in contexts of social
      change.
AB  - The paper explores the implications for health policy of the segmentation of
      society into social groups with very different levels of income and wealth.
      Discourses on equity in health are presently dominated by a debate between
      'European' and 'American' models of health delivery. This has led to a focus on
      ideal outcomes rather than practical options for organising and financing health
      services in poor countries undergoing rapid change. The paper argues for a more
      explicit acknowledgement of the dynamic character of health development and the
      political nature of the negotiations regarding the use of government powers.
      Unregulated markets for health care are neither equitable nor efficient.
      Government must play a role in supporting the organisation of health services
      used by different social groups. Countries with low levels of inequality may be
      able to provide universal access to relatively sophisticated health services.
      Otherwise, governments need to operate within a segmented system. This means the
      negotiation of strategies to reduce the burden of sickness and premature death,
      whilst meeting the needs of different social groups. The discussion is organised
      in terms of the powers of government to require individuals and institutions to
      transfer resources for social uses, enforce regulations and generate and
      disseminate information. The paper concludes that governments committed to equity
      enhancing health development need to increase their capacity to facilitate
      coalition building and manage change. It proposes an international public health
      legal framework that might include a definition of minimum standards for certain
      health services, to be underwritten by national and international financial
      commitments.

PMID- 11459628
TI  - Equivalence versus pragmatic trials for the economic evaluation of information
      and communication technologies; the case of polysomnography under
      telesurveillance in the diagnosis of sleep apnea syndrome.
AB  - This article deals with the choice of the appropriate protocols for the early
      economic evaluation of information and communication technologies, equivalence
      trial versus pragmatic trial. The reasoning put forward here is based on a
      concrete interrogation relative to polysomnography (PSG), a key diagnostic test
      for sleep apnoea syndrome (SAS). Is PSG under tele-surveillance more efficient
      than ambulatory PSG to diagnose SAS? After analyzing and discussing both
      advantages and limits of these two kinds of trial, we showed that one or the
      other can be used to obtain appropriate results. But in this particular example,
      we concluded that a pragmatic trial should be preferred, knowing that it requires
      a smaller sample of patients along with a narrower range of uncertainty
      concerning the evaluation of costs.

PMID- 11459629
TI  - Improving performance in public hospitals: a role for comparative costs?
AB  - In order to encourage performance improvements, the English government has set
      targets for acute hospitals to reduce their unit costs. Targets are based on
      analysis of costs across all acute hospitals. This policy has parallels with that
      of 'yardstick competition', advocated as a means to encourage efficiency in
      industries that lack competitive pressures. However, the prospect of cost
      improvements may not be realised in England. Firstly, there are insufficient
      incentives to respond appropriately to the provision of comparative cost
      information. Secondly, there is more than one index purporting to measure
      relative hospital costs. As comparison of unit costs is highly dependent on the
      measurement technique adopted, caution should be exercised when setting
      performance targets.

PMID- 11459630
TI  - DNA postreplication repair and mutagenesis in Saccharomyces cerevisiae.
AB  - DNA postreplication repair (PRR) is defined as an activity to convert DNA damage
      induced single-stranded gaps into large molecular weight DNA without actually
      removing the replication-blocking lesions. In bacteria such as Escherichia coli,
      this activity requires RecA and the RecA-mediated SOS response and is
      accomplished by recombination and mutagenic translesion DNA synthesis. Eukaryotic
      cells appear to share similar DNA damage tolerance pathways; however, some
      enzymes required for PRR in eukaryotes are rather different from those of
      prokaryotes. In the yeast Saccharomyces cerevisiae, PRR is centrally controlled
      by RAD6 and RAD18, whose products form a stable complex with single-stranded DNA
      binding, ATPase and ubiquitin-conjugating activities. PRR can be further divided
      into translesion DNA synthesis and error-free modes, the exact molecular events
      of which are largely unknown. This error-free PRR is analogous to DNA damage
      avoidance as defined in mammalian cells, which relies on recombination processes.
      Two possible mechanisms by which recombination participate in PRR to resolve the
      stalled replication folk are discussed. Recombination and PRR are also
      genetically regulated by a DNA helicase and are coupled to the cell-cycle. The
      PRR processes appear to be highly conserved within eukaryotes, from yeast to
      human.

PMID- 11459631
TI  - Direct transfer of Ku between DNA molecules with nonhomologous ends.
AB  - The Ku protein is an essential protein for DNA double-strand-break repair by the
      pathway of nonhomologous DNA end-joining (NHEJ). A previous study showed that Ku
      bound to one DNA molecule could transfer directly to another DNA molecule without
      being released into the solution first. Direct transfer requires the two DNA
      molecules having homologous cohesive ends with a minimum of four complementary
      bases. Results of this study reveal that direct transfer activity of Ku is
      regulated by NaCl and MgCl2. Increasing either one of the two cations can
      decrease the required amount of the other. However, the DNA end-binding activity
      of Ku is not affected by changing the concentration of the cations, indicating
      that the two activities are regulated independently. Most importantly, the
      results also show that Ku can transfer directly from one DNA molecule to another
      one with nonhomologous ends under the condition of 200 mM NaCl and 5mM MgCl2. The
      ability of direct transfer between DNAs with nonhomologous ends suggests that Ku
      can align or juxtapose two DNA ends during NHEJ.

PMID- 11459632
TI  - Interaction of the yeast Pso5/Rad16 and Sgs1 proteins: influences on DNA repair
      and aging.
AB  - The interaction trap method was used to isolate putative binding partners of
      Rad16/Pso5, a protein responsible for repair of silent DNA. One of the
      interactors found was Sgs1, a DNA helicase influencing the life span of
      Saccharomyces cerevisiae, with homology to the human BLM, WRN and RECQL4
      proteins. Using the same fusion proteins from the two-hybrid screening, we show
      evidence that both proteins also interact in vitro. We tested isogenic strains,
      containing mutant alleles of the two genes in single and double mutant
      combination, for phenotypic similarity. Life span in sgs1Delta single and
      sgs1Delta rad16Delta double mutants is about 40% of that of WT, and the
      rad16/pso5Delta single mutant also had its life span reduced to 75%. Sensitivity
      to different mutagens, whose lesions are poorly repaired in rad16/pso5Delta
      mutants, was tested in sgs1Delta mutants. The sgs1Delta conferred sensitivity to
      MMS, H2O2 and was moderately sensitive to UV(254nm) (UVC) and 4-NQO. An epistatic
      interaction between rad16 and sgs1 mutations after UVC, 4-NQO and H2O2 was
      observed. Moreover, we found that in a top3 background, functional Sgs1p and
      Rad16p apparently channel MMS, 4-NQO and H2O2 induced lesions into aberrant DNA
      repair. Our results demonstrate that Sgs1 is not only involved in genome
      stability, somatic recombination and aging, but is also implicated, together with
      Rad16/Pso5, in the repair of specific DNA damage.

PMID- 11459633
TI  - DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes
      is not dependent on genetic polymorphism Ser326/Cys326.
AB  - 8-oxoguanine DNA glycosylase 1 (OGG1) is a DNA repair enzyme that excises 7,8
      dihydro-8-oxoguanine (8oxoG) from DNA. Since 8oxoG is a highly mispairing lesion,
      decreased OGG1 expression level could lead to a higher background mutation
      frequency and could possibly increase the cancer risk of an individual under
      oxidative stress. In order to analyse the natural variation of OGG1, we measured
      the DNA repair activity in human lymphocytes of healthy individuals by means of
      an 8oxoG-containing oligonucleotide assay. The data obtained revealed a two fold
      interindividual variation of OGG1 activity in lymphocytes. There was no
      difference in OGG1 activity due to gender and smoking behaviour. Transcriptional
      analyses of OGG1 showed the expression of two isoforms, 1a and b, in lymphocytes.
      Structural analysis of the human OGG1 (hOGG1) gene revealed a Ser326/Cys326
      polymorphism in the Caucasian population with allele frequencies of 75% for
      Ser326 and 25% for Cys326. This polymorphism was not associated with altered OGG1
      activity. The described routine test system for measuring OGG1 activity in
      cryopreserved lymphocytes provided highly reproducible results and is a useful
      tool for risk assessment associated with alterations in the repair of oxidative
      DNA damage.

PMID- 11459634
TI  - Development of potent and selective factor Xa inhibitors.
AB  - The development of potent and selective small molecule inhibitors of factor Xa is
      described.

PMID- 11459635
TI  - Neutral inhibitors of the serine protease factor Xa.
AB  - A neutral inhibitor of the serine protease factor Xa was identified via a high
      throughput screen of a commercial library. The initial lead 1 demonstrated
      reversible and competitive inhibition kinetics for factor Xa and possessed a high
      degree of selectivity versus other related serine proteases. Initial modeling
      efforts and the generation of a series of analogues of 1 are described.

PMID- 11459636
TI  - Novel tricyclic benzothiazolo[2,3-c]thiadiazine antagonists of the platelet ADP
      receptor (P2Y(12)).
AB  - Novel non-nucleoside tricyclic platelet ADP receptor (P2Y(12)) antagonists have
      been discovered that bind reversibly and with high affinity to the platelet
      receptor. Condensation of various 2-aminobenzothiazoles with chlorosulfonylacetyl
      chloride affords these novel tricyclic heterocycles, which are novel and
      unpredicted products of this reaction.

PMID- 11459637
TI  - Inhibition of fucosyltransferase V by a GDP-Azasugar.
AB  - A GDP-azasugar conjugate was synthesized starting from an enzymatically obtained
      phosphorylated azasugar. It inhibits human fucosyltransferase V at micromolar
      concentrations, which is discussed in terms of transition state analogy.

PMID- 11459638
TI  - In vitro and In vivo inhibition of LPS-stimulated tumor necrosis factor-alpha
      secretion by the gallotannin beta-D-pentagalloylglucose.
AB  - The naturally occurring gallotannin beta-D-pentagalloylglucose (beta-PGG)
      decreases tumor necrosis factor-alpha (TNF-alpha) output from human peripheral
      blood mononucleocytes exposed to lipopolysaccharide (LPS) by as much as 90% (vs
      control) at approximately 5 microM concentration. A qualitatively similar but
      less pronounced effect ( approximately 50% decrease) was observed in the serum of
      rats dosed with both LPS and beta-PGG. These results may have relevance to
      therapies that target disease states characterized by an overproduction of TNF
      alpha.

PMID- 11459639
TI  - Evaluation of amino acid-based linkers in potent macrocyclic inhibitors of
      farnesyl-protein transferase.
AB  - A series of amino acid-based linkers was used to investigate the effects of
      various substituents upon the potency, pharmacokinetic properties, and
      conformation of macrocyclic farnesyl-protein transferase inhibitors (FTIs). As a
      result of the studies described herein, highly potent FTIs with improved
      pharmacokinetic profiles have been identified.

PMID- 11459640
TI  - Nitrobenzene compounds inhibit expression of VCAM-1.
AB  - A series of nitrobenzene compounds has been discovered as potent inhibitors of
      VCAM-1 expression and, therefore, potential drug candidates for autoimmune and
      allergic inflammatory diseases. Structure-activity relationship (SAR) studies
      showed that a nitro group and two other electron-withdrawing groups are essential
      for these compounds to be potent inhibitors of VCAM-1 expression.

PMID- 11459641
TI  - Novel piperidinyloxy oxazolidinone antimicrobial agents.
AB  - Oxazolidinone antibacterial agents, where the N-substituted piperazinyl group of
      eperezolid was replaced with a N-substituted piperidinyloxy moiety, were
      synthesized and shown to be active against a variety of resistant and susceptible
      Gram-positive organisms. The effect of ring size, positional isomerism, and
      fluorine substitution on antibacterial activity was examined.

PMID- 11459642
TI  - Design and synthesis of novel benzofurans as a new class of antifungal agents
      targeting fungal N-myristoyltransferase. Part 1.
AB  - Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors
      have been identified through optimization of a lead compound 1 discovered by
      random screening. The inhibitor design is based on the crystal structure of the
      CaNmt complex with compound (S)-3 and structure-activity relationships (SARs)
      have been clarified. Modification of the C-4 side chain of 1 has led to the
      discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which
      exhibits antifungal activity against C. albicans in vitro.

PMID- 11459643
TI  - Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): structure
      requirement of hydroxyanthraquinones for estrogenic activity.
AB  - The methanolic extract from the roots of Polygonum (P.) cuspidatum was found to
      enhance cell proliferation at 30 or 100 microg/mL in MCF-7, an estrogen-sensitive
      cell line. By bioassay-guided separation from P. cuspidatum with the most potent
      activity, emodin and emodin 8-O-beta-D-glucopyranoside were isolated as active
      principles. The methanolic extracts from Polygonum, Cassia, Aloe, and Rheum
      species, which were known to contain anthraquinones, also showed the MCF-7
      proliferation. As a result of the evaluation of various anthraquinones from plant
      sources and synthetic anthraquinones, aloe-emodin, chrysophanol, chrysophanol 8-O
      beta-D-glucopyranoside, and 1,8-dihydroxyanthraquinone showed weak activity. On
      the other hand, alizalin and 2,6-dihydroxyanthraquinone as well as emodin having
      the 2- and/or 6-hydroxyl groups showed potent activity. These results show that
      the unchelated hydroxyl group is essential for strong activity. Emodin and 2,6
      dihydroxyanthraquinone also inhibited 17beta-estradiol binding to human estrogen
      receptors (ERs) with K(i) values of 0.77 and 0.31microM for ERalpha and 1.5 and
      0.69 microM for ERbeta. These findings indicate that hydroxyanthraquinones such
      as emodin are phytoestrogens with an affinity to human estrogen receptors.

PMID- 11459644
TI  - Synthesis and biological activity of novel macrocyclic antifungals. modification
      of the tyrosine moiety of the lipopeptidolactone FR901469.
AB  - A series of tyrosine-modified derivatives of the macrocyclic lipopeptidolactone
      FR901469 have been prepared and evaluated for in vitro and in vivo antifungal
      activity and for hemolytic activity towards red blood cells. Compound 14
      displayed significantly reduced hemolytic potential at 1mg/mL and a comparable
      protective effect to FR901469 in a mouse candidiasis model.

PMID- 11459645
TI  - Design, synthesis, and biological evaluation of a series of simple and novel
      potential antimalarial compounds.
AB  - A series of compounds bearing an endocyclic -N-O- moiety with potential
      antimalarial activity based on simple derivatives of the tropolone purpurogallin
      was prepared by means of a hetero Diels-Alder reaction using nitrosobenzene as a
      dienophile. The rationale behind the design of these compounds is presented,
      together with the synthetic route to derivatives bearing aromatic and aliphatic
      esters of the C4'-position hydroxyl group of the purpurogallin framework, as well
      as biological data obtained from in vitro assays against Plasmodium falciparum
      and Trypanosoma cruzi. Several of the new compounds have activities in the 3-9
      microM range, and provide leads for the development of a novel class of
      antiparasitic drugs with improved biological and pharmacological properties.

PMID- 11459646
TI  - Diaminopurine-acridine heterodimers for specific recognition of abasic site
      containing DNA. Influence on the biological activity of the position of the
      linker on the purine ring.
AB  - Three acridine-diaminopurine heterodimers tethered by a linker containing an N,N'
      substituted guanidine were prepared. The molecules differ by the site of
      introduction of the linker on the 2,6-diaminopurine. The interactions of the new
      heterodimers with abasic site containing oligonucleotide were compared, and their
      cytotoxicity was measured in the presence or absence of the antitumor alkylating
      agent BCNU.

PMID- 11459647
TI  - Synthesis of oxorhenium(V) and oxotechnetium(V) [SN(R)S/S] mixed ligand complexes
      containing a phenothiazine moiety on the tridentate SN(R)S ligand.
AB  - Two oxorhenium and two oxotechnetium [SN(R)S/S] mixed ligand complexes bearing
      the phenothiazine moiety on the tridentate ligand SN(R)S have been synthesized
      and characterized. The corresponding complexes at tracer level (99mTc) have also
      been prepared.

PMID- 11459648
TI  - Preparation of oligonucleotides without aldehyde abasic sites.
AB  - High-quality oligonucleotides are obtained by selective modification of sequences
      containing aldehyde apurinic sites with a new chromatographic tag followed by RP
      HPLC separation. Hydroxylamine derivative 1 of a water soluble nonionic
      surfactant modifies oligonucleotides selectively at abasic sites leading to
      significantly increased retention.

PMID- 11459649
TI  - Pyrazinone conjugates as potential cephalosporin allergens.
AB  - Cephalosporins with an alpha-amino group on the 7-beta-acyl substituent have been
      shown to undergo aminolysis with subsequent formation of a fluorescent pyrazinone
      degradation product. An analogous reaction seems to take place upon in vitro
      conjugation of such cephalosporins to albumins and polylysine. A corresponding
      pyrazinone-polylysine conjugate was able to bind IgE antibodies in sera from
      patients with suspected allergy to beta-lactams. These findings may have
      applications in the diagnosis of allergy against aminocephalosporins.

PMID- 11459650
TI  - Synthesis and biological evaluation of didemnin photoaffinity analogues.
AB  - The synthesis of four benzophenone-containing analogues of the antiproliferative
      natural product didemnin B is presented. In vitro protein biosynthesis inhibition
      potency and antitumor activity were evaluated. The results indicate that all four
      analogues are biologically active and could serve as photoaffinity reagents for
      the study of receptor-binding interactions of didemnins. These analogues could
      also be useful in studying antitumor effects of didemnins.

PMID- 11459651
TI  - N-acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal
      agents.
AB  - We describe herein the synthesis, bioconversion, antifungal activity, and
      preliminary toxicology evaluation of a series of N-acyloxymethyl carbamate linked
      triprodrugs of pseudomycins. The syntheses of these prodrugs (3-6) were achieved
      via simple N-acylation of PSB (1) or PSC' (2) with various prodrug linkers (7-9).
      As expected, upon incubation with mouse and/or human plasma, many of these
      prodrugs (3, 5, and 6) were converted to the parent compound within a few hours.
      Of particular significance, two pseudomycin triprodrugs (5 and 6) showed
      excellent in vivo efficacy against systemic Candidiasis without tail vein
      irritation being observed.

PMID- 11459652
TI  - Prodrugs of 3-amido bearing pseudomycin analogues: novel antifungal agents.
AB  - With the aim of identifying safer pseudomycin derivatives, we synthesized and
      evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido
      pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations
      prepared exhibited good in vivo efficacy against murine Candidiasis. When
      evaluated in a dose elevation study, all of the newly synthesized combinations
      (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison
      to their corresponding 3-amides as well as the parent pseudomycin B.

PMID- 11459653
TI  - Studies towards the next generation of antidepressants. Part 1:
      Indolylcyclohexylamines as potent serotonin reuptake inhibitors.
AB  - A series of indolylcyclohexylamines possessing potent and selective serotonin
      reuptake inhibition is reported. The most interesting compounds proved to have
      subnanomolar 5-HT transporter activity, and exhibited moderate 5-HT(1A) affinity.

PMID- 11459654
TI  - Macrocyclization in the design of a conformationally constrained Grb2 SH2 domain
      inhibitor.
AB  - Grubbs' olefin metathesis reaction was utilized to prepare a macrocyclic variant
      of a linear Grb2 SH2 domain antagonist in an attempt to induce a beta-bend
      conformation known to be required for high affinity binding. In extracellular
      Grb2 SH2 domain binding assays, the macrocyclic analogue exhibited an approximate
      100-fold enhancement in binding potency relative to its linear counterpart. The
      macrocycle was not as effective in whole cell binding assays as would be expected
      based on its extracellular binding potency.

PMID- 11459655
TI  - Carbohydrate recognition of gramicidin S analogues in aqueous medium.
AB  - We have designed and synthesized of carbohydrate-binding peptides, gramicidin S
      analogues. Asn/Asp/Gln and Trp residues in the peptides were employed as the
      binding sites for carbohydrates by hydrogen-bonding interaction and the creation
      units for hydrophobic pocket to promote the interaction, respectively. The data
      of fluorescence spectroscopy and affinity column chromatography indicated that
      the peptides possessed the binding ability for some carbohydrates in aqueous
      medium. As a result of 1H NMR study, nuclear Overhauser effects between aromatic
      side chains of a peptide, [Gln(1,1'),Trp(3,3')]-gramisidin S and mannose were
      observed, indicating that the interaction of the peptide with the sugar occurred
      in the hydrophobic environment formed by Trp and Phe residues.

PMID- 11459656
TI  - Development of specific CXCR4 inhibitors possessing high selectivity indexes as
      well as complete stability in serum based on an anti-HIV peptide T140.
AB  - We previously reported a truncated polyphemusin peptide analogue, T140, which
      efficiently inhibits infection of target cells by T-cell line-tropic strains of
      HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. We
      have found that T140 is not stable in feline serum due to the cleavage of the C
      terminal Arg,(14) indispensable for anti-HIV activity. On the other hand, a C
      terminally amidated analogue of T140, TZ14004, has been found to be completely
      stable in incubation in the serum for 2 days. The C-terminal amide is thought to
      be needed for stability in serum. However, TZ14004 does not have fairly strong
      anti-HIV activity, but has relatively strong cytotoxicity, probably due to an
      increase by +1 charge from total +7 charges of T140. In our previous study, the
      number of total +6 charges seemed to be a suitable balance between activity and
      cytotoxicity. In this study, we have conducted a double-L-citrulline (Cit)
      scanning study on TZ14004 based on the C-terminally amidated form in due
      consideration of the total net charges in the whole molecule to find novel
      effective CXCR4 inhibitors, TN14003 ([Cit(6)]-T140 with the C-terminal amide) and
      TC14012 ([Cit(6), D-Cit(8)]-T140 with the C-terminal amide), which possess high
      selectivity indexes (SIs) and complete stability in feline serum.

PMID- 11459657
TI  - 3-Arylpiperidines as potentiators of existing antibacterial agents.
AB  - Important resistance patterns in Gram-negative pathogens include active efflux of
      antibiotics out of the cell via a cellular pump and decreased membrane
      permeability. A 3-arylpiperidine derivative (1) has been identified by high
      throughput assay as a potentiator with an IC(50) approximately 90 microM. This
      report details the evaluation of the tether length, aryl substitution and the
      importance of the fluorine on antibiotic accumulation. Evaluation of various
      tether lengths demonstrated that the two-carbon tethered analogues are optimal.
      Removal of the fluorine has a modest effect on antibiotic accumulation and the
      defluorinated analogue 17 is equally potent to the original lead 1.

PMID- 11459658
TI  - 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor.
AB  - This communication reports SARs for the first orexin-1 receptor antagonist series
      of 1-aryl-3-quinolin-4-yl and 1-aryl-3-naphthyridin-4-yl ureas. One of these
      compounds, 31 (SB-334867), has excellent selectivity for the orexin-1 receptor,
      blood-brain barrier permeability and shows in vivo activity following ip dosing.

PMID- 11459659
TI  - Studies leading to the identification of ZD1839 (IRESSA): an orally active,
      selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to
      the treatment of cancer.
AB  - This paper describes the development of the epidermal growth factor receptor
      tyrosine kinase inhibitor ZD1839 from a lead series of 4-anilinoquinazoline
      compounds. ZD1839 has suitable properties for use as a clinically effective drug
      and shows activity against human tumours. In particular, the use of
      pharmacokinetic data in the development of ZD1839 is discussed.

PMID- 11459660
TI  - Highly potent growth hormone secretagogues: hybrids of NN703 and ipamorelin.
AB  - A series of NN703 analogues with lysine mimetics combined with naphthyl- or
      biphenylalanine in the core has been prepared and tested in vitro in a rat
      pituitary cell based assay and subsequently in vivo in pigs in a single dose at
      50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703,
      which were originally removed during optimisation for oral bioavailability, led
      to unexpectedly potent compounds in vitro as well as in vivo.

PMID- 11459661
TI  - Synthesis of N(1)-substituted analogues of (2R,4R)-4-amino-pyrrolidine-2,4
      dicarboxylic acid as agonists, partial agonists, and antagonists of group II
      metabotropic glutamate receptors.
AB  - The chemical synthesis of a series of N(1)-substituted derivatives of (2R,4R)-4
      aminopyrrolidine-2,4-dicarboxylic acid [(2R,4R)-APDC] as constrained analogues of
      gamma-substituted glutamic acids is described. Appropriate substitution of the
      N(1)-position results in agonist, partial agonist, or antagonist activity at
      mGluR2, mGluR3, and/or mGluR6.

PMID- 11459662
TI  - 1-(Arylpiperazinylamidoalkyl)-pyrimidones: orally active inhibitors of
      lipoprotein-associated phospholipase A(2).
AB  - The lipophilic 1-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones,
      inhibitors of recombinant lipoprotein-associated phospholipase A(2), has been
      modified to give inhibitors of high potency in human plasma and enhanced
      physicochemical properties. Phenylpiperazineacetamide derivative 23 shows very
      promising oral activity.

PMID- 11459663
TI  - Introduction of alkynyl chains on C-8 of adenosine led to very selective
      antagonists of the A(3) adenosine receptor.
AB  - Some 8-alkynyladenosines were synthesized and evaluated for their adenosine
      receptor activity, utilizing radioligand binding studies (A(1), A(2A), A(3)) or
      adenylyl cyclase activity assays (A(2B)). Furthermore, the maximal induction of
      guanosine 5'-(gamma-thio)triphosphate ([35S]GTPgammaS) binding to G proteins and
      the inhibition of NECA-stimulated binding, in membranes of CHO cells which
      express the human A(3) receptor, were used to determine the intrinsic activity of
      these nucleosides at the A(3) adenosine receptor. The results showed that these
      new adenosine derivatives are very selective ligands for the A(3) receptor
      subtype and behave as adenosine antagonists, since they do not stimulate basal
      [35S]GTPgammaS binding, but inhibit NECA-stimulated binding. This is the first
      report that adenosine derivatives, with unmodified ribose moiety, are adenosine
      receptor antagonists.

PMID- 11459664
TI  - alpha-Ketocarboxylic acid-based inhibitors of protein tyrosine phosphatases.
AB  - A series of aryl alpha-ketocarboxylic acids was synthesized and investigated as
      inhibitors for the protein tyrosine phosphatase from Yersinia enterocolitica.
      IC(50) values for these compounds range from 79 to 2700 microM. Larger aromatic
      groups, and aromatic groups with high electron density, lead to more potent
      inhibitors. In general, the related aryl alpha-hydroxycarboxylic acids show lower
      activity.

PMID- 11459665
TI  - 2-Amino-4,6-diarylpyridines as novel ligands for the estrogen receptor.
AB  - We have prepared a novel series of 2-amino-4,6-diarylpyridines that function as
      ligands of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta).
      These compounds bind to both ERalpha and ERbeta with a modest selectivity for the
      alpha subtype. The most potent of these analogues, compound 19, has a K(i)=20nM
      at ERalpha. These molecules represent a novel template for designing potentially
      useful ligands for the estrogen receptor.

PMID- 11459666
TI  - Synthesis and evaluation of novel quinolinones as HIV-1 reverse transcriptase
      inhibitors.
AB  - A series of 4,4-disubstituted quinolinones was prepared and evaluated as HIV-1
      reverse transcriptase inhibitors. The C-3 substituted compound 9h displayed
      improved antiviral activity against clinically significant single (K103N) and
      double (K103N/L100I) mutant viruses.

PMID- 11459667
TI  - Selectivity enhancement induced by substitution of non-natural analogues of
      arginine and lysine in arginine-based thrombin inhibitors.
AB  - Seven non-natural analogues of arginine and lysine have been substituted in an
      established arginine-based thrombin inhibitor. Four of the new compounds
      exhibited significant thrombin inhibition (K(i)'s 0.53-3.95 microM) and were
      subsequently tested for selectivity against trypsin. The two best compounds gave
      selectivity ratios of 962 and 525 (trypsin/thrombin), improving upon the parent
      compound.

PMID- 11459668
TI  - Nicotinamide N-oxides as CXCR2 antagonists.
AB  - A series of nicotinamide N-oxides was synthesized and shown to be novel, potent,
      and selective antagonists of the CXCR2 receptor. Furthermore, these compounds
      showed significant functional activity against GRO-alpha-driven human neutrophil
      chemotaxis. Compounds of this class may be useful for the treatment of
      inflammatory, auto-immune, and allergic disorders.

PMID- 11459669
TI  - Spiro(indoline-3,4'-piperidine) growth hormone secretagogues as ghrelin mimetics.
AB  - A series of small molecules derived from MK-0677, a potent synthetic GHS,
      mimicking the N-terminal Gly-Ser-O-(n-octanoyl)-L-Ser-Phe segment of ghrelin was
      synthesized and tested in a binding and in a functional assay measuring
      intracellular calcium elevation in HEK-293 cells expressing hGHSR1a. Replacement
      of Phe in this tetrapeptide with a spiro(indoline-3,4'-piperidine) group, Gly-Ser
      with 2-aminoisobutyric acid, and O-(n-octanoyl)-L-Ser with O-benzyl-D-Ser
      provided synthetic GHS agonists with similar functional potency as ghrelin.

PMID- 11459670
TI  - Cyclic imides as potent and selective alpha-1A adrenergic receptor antagonists.
AB  - We disclose a new compound class of potent and selective alpha-1A adrenergic
      receptor antagonists exemplified by the geminally, disubstituted cyclic imide 7.
      The optimization of lead compounds resulting in the cyclic imide motif is
      highlighted. The results of in vitro and in vivo studies of selected compounds
      are presented.

PMID- 11459673
TI  - Abstracts of the 5th Annual ESCV (European Society for Clinical Virology)
      Meeting. 2 September 2001, Lahti, Finland.

PMID- 11459675
TI  - The 'motor' inaccuracy in neurogenic motor evoked potentials.

PMID- 11459676
TI  - Therapeutic application of repetitive transcranial magnetic stimulation: a
      review.
AB  - Transcranial magnetic stimulation (TMS), a non-invasive means of electrically
      stimulating neurons in the human cerebral cortex, is able to modify neuronal
      activity locally and at distant sites when delivered in series or trains of
      pulses. Data from stimulation of the motor cortex suggest that the type of effect
      on the excitability of the cortical network depends on the frequency of
      stimulation. These data, as well as results from studies in rodents, have been
      generalized across brain areas and species to provide rationales for using
      repetitive TMS (rTMS) to treat various brain disorders, most notably depression.
      Research into clinical applications for TMS remains active and has the potential
      to provide useful data, but, to date, the results of blinded, sham-controlled
      trials do not provide clear evidence of beneficial effects that replace or even
      match the effectiveness of conventional treatments in any disorder. In this
      review, we discuss the clinical and scientific bases for using rTMS as treatment,
      and review the results of trials in psychiatric and neurological disorders to
      date.

PMID- 11459677
TI  - Recurrent neural network-based approach for early recognition of Alzheimer's
      disease in EEG.
AB  - OBJECTIVE: We explored the ability of specifically designed and trained recurrent
      neural networks (RNNs), combined with wavelet preprocessing, to discriminate
      between the electroencephalograms (EEGs) of patients with mild Alzheimer's
      disease (AD) and their age-matched control subjects. METHODS: Twomin recordings
      of resting eyes-closed continuous EEGs (as well as their wavelet-filtered
      subbands) obtained from parieto-occipital channels of 10 early AD patients and 10
      healthy controls were input into RNNs for training and testing purposes. The RNNs
      were chosen because they can implement extremely non-linear decision boundaries
      and possess memory of the state, which is crucial for the considered task.
      RESULTS: The best training/testing results were achieved using a 3-layer RNN on
      left parietal channel level 4 high-pass wavelet subbands. When trained on 3 AD
      and 3 control recordings, the resulting RNN tested well on all remaining controls
      and 5 out of 7 AD patients. This represented a significantly better than chance
      performance of about 80% sensitivity at 100% specificity. CONCLUSION: The
      suggested combined wavelet/RNN approach may be useful in analyzing long-term
      continuous EEGs for early recognition of AD. This approach should be extended on
      larger patient populations before its clinical diagnostic value can be
      established. Further lines of investigation might also require that EEGs be
      recorded from patients engaged in certain mental (cognitive) activities.

PMID- 11459678
TI  - Time-variant non-linear phase-coupling analysis of EEG burst patterns in sedated
      patients during electroencephalic burst suppression period.
AB  - OBJECTIVES: The quadratic phase-coupling (QPC) within burst patterns during
      electroencephalic burst suppression has been quantified. METHODS: It can be shown
      that a QPC exists between the frequency ranges 0-2.5 and 3-7.5 Hz and between the
      frequency ranges 0-2.5 and 8-12 Hz. By means of time-variant bicoherence
      analysis, a strong phase-locking between the modulating and the modulated
      component can be identified. The phase-locking is demonstrable within the first
      250 ms after the burst onset and comes up to the maximum between 750 and 1250 ms.
      RESULTS: The effect is maintained over the whole first part of the burst (2 s)
      with a decreasing tendency after 1250 ms. All these effects cannot be found in
      the EEG before entering the burst suppression period (BSP). The transient
      coupling phenomena in the EEG bursts during BSP can be regarded as indicators for
      short-term interrelations between the underlying electrophysiologic processes.
      CONCLUSIONS: It can be suggested that the method introduced for the
      quantification of the sedation depth should be used.

PMID- 11459679
TI  - Boundary element method volume conductor models for EEG source reconstruction.
AB  - OBJECTIVES: The boundary element method (BEM) approximates the different
      compartments of volume conductor models by closed triangle meshes with a limited
      number of nodes. The shielding effect of the weakly conducting skull layer of the
      human head leads to decreasing potential gradients from the inside to the
      outside. Thus, there may be an optimum distribution of nodes to the compartments
      for a given number of nodes corresponding to a fixed computational effort,
      resulting in improved accuracy as compared to standard uniform distributions.
      METHODS: Spherical and realistically shaped surfaces are approximated by 500,
      1000, 2000, and 3000 nodes, each leading to BEM models with 1500-9000 nodes in
      total. Electrodes are placed on extended 10/20-system positions. Potential
      distributions of test-dipoles at 4000 random positions within the innermost
      compartment are calculated. Dipoles are then fitted using 192 different models to
      find the optimum node distribution. RESULTS: Fitted dipole positions for all BEM
      models are evaluated to show the dependency of the averaged and maximum
      localization errors on their node distributions. Dipoles close to the innermost
      boundary exhibit the largest localization errors, which mainly depend on the
      refinement of this compartment's triangle mesh. CONCLUSIONS: More than 500 nodes
      per compartment are needed for reliable BEM models. For a state-of-the-art model
      consisting of 6000 nodes overall, the best model consists of 3000, 2000, and 1000
      nodes from the inside to the outside.

PMID- 11459680
TI  - Tracing of proximal lumbosacral nerve conduction--a comparison of simultaneous
      magneto- and electroneurography.
AB  - OBJECTIVE: The reconstruction of nerve impulse conduction along proximal
      lumbosacral plexus and nerve roots is compared using simultaneous magneto- and
      electroneurography. METHODS: In 3 healthy subjects the left tibial nerve was
      electrostimulated at the ankle. Evoked magnetic fields and electric surface
      potentials were measured simultaneously over the lumbosacral spine using a
      multichannel SQUID-detector with a planar measuring area and 25 surface
      electrodes covering a comparable area centered around L4. Based on either
      magnetic field or electric potential maps the depolarization front of the evoked
      compound action currents (CAC) was spatio-temporally reconstructed using a simple
      equivalent current dipole model in a half-space volume conductor. RESULTS: The
      mean signal-to-noise ratio in the magnetic (electric) recordings was around 4
      (8). Yet, the localization quality for the propagating CAC was lower for electric
      than magnetic recordings. The local nerve conduction velocity was around 47 m/s
      (calculated from magnetic data), but fluctuated unphysiologically for electric
      data. CONCLUSION: In comparison to electroneurography, an anatomically reasonable
      localization of evoked compound action currents propagating in lumbosacral roots
      can be obtained by magnetoneurography.

PMID- 11459681
TI  - Determinants of pain in needle electromyography.
AB  - OBJECTIVES: Although previous literature has attempted to characterize patients'
      pain during electromyography (EMG) based on the size and type of needle used,
      none have assessed the relationship between the needle insertion technique and
      pain. METHODS: The effects of needle type and needle movement within muscle on
      the immediate and residual pain during needle EMG were measured in a double-blind
      study of 48 patients with diverse clinical problems but no sensory loss. RESULTS:
      The results demonstrate that when using a standard insertion technique
      characterized by large needle movement, the monopolar needles were less painful
      than concentric needle electrodes. However, when using small needle movements (1
      mm or less), pain associated with concentric needles was significantly reduced
      with no difference between the needle types. Examiner experience, gender,
      previous EMG, reported pain tolerance, pain on nerve conduction studies and other
      factors did not predict the amount of pain. The type of needle and type of needle
      movement did not effect the sensitivity of identifying abnormalities.
      CONCLUSIONS: These findings would support the hypothesis that although a
      monopolar needle electrode is less painful when using a standard technique, the
      needle-handling technique, specifically small needle movements, plays a large
      role in determining pain when using concentric needle electrodes.

PMID- 11459682
TI  - Alpha band power changes in unimanual and bimanual sequential movements, and
      during motor transitions.
AB  - OBJECTIVE: To investigate the cortical activation during execution of unimanual
      and bimanual synchronous and asynchronous finger sequences, as well as during
      transitions between those sequences. METHODS: Task-related power (TRPow) analysis
      of multichannel surface EEG was used to examine the regional oscillatory brain
      activity in the lower (7.8-9.8 Hz) and upper (10.8-11.8 Hz) alpha band. Unimanual
      to bimanual, bimanual to unimanual, and unimanual to unimanual transitions,
      prompted by visual cues, were studied in 10 right handed subjects. RESULTS: (1)
      Execution of unimanual and bimanual movements was accompanied by a bilateral
      activation over the central regions. (2) The 7.8-9.8 Hz TRPow decrease was more
      prominent for left and bimanual movements, suggesting sensitivity of the lower
      alpha band to task difficulty. (3) No difference in alpha oscillatory activity
      was found between bimanual synchronous and asynchronous sequences. (4)
      Transitions between motor sequences were invariably accompanied by a
      mesioparietal TRPow decrease in the lower alpha band. (5) This mesioparietal
      activation was contingent to the change of motor program, and could not be
      accounted for by the change of visual cue, or related attentional processes.
      CONCLUSION: The 7.8-9.8 Hz mesioparietal activation most likely reflects a
      posterior parietal motor command initiating transition between motor programs.

PMID- 11459683
TI  - Motor cortex disinhibition in Alzheimer's disease.
AB  - OBJECTIVES: To explore subclinical disturbances in the motor cortex of patients
      with Alzheimer's disease (AD). METHODS: We used transcranial magnetic stimulation
      in a paired pulse technique to test intracortical inhibition (ICI) and
      intracortical facilitation in mildly to moderately demented AD patients with a
      normal neurological examination. Patients were studied before and during
      treatment with the cholinesterase inhibitor donepezil. RESULTS: AD patients had a
      reduced ICI compared to an age-matched control group. The amount of disinhibition
      correlated with the severity of dementia. Treatment with 10 mg donepezil daily
      was associated with an increase of ICI. CONCLUSIONS: The subclinical motor cortex
      disinhibition in AD patients indicates a functional disturbance, and is probably
      associated with a cholinergic deficit.

PMID- 11459684
TI  - Anterior spinal cord injury with preserved neurogenic 'motor' evoked potentials.
AB  - OBJECTIVE: To describe two cases in which intraoperative monitoring of neurogenic
      'motor' evoked potentials (NMEPs) did not identify a spinal cord injury that
      resulted in paraplegia. METHODS: Bilateral tibial nerve somatosensory evoked
      potential (SEP) and NMEP testing was performed in two patients during spinal
      deformity corrective surgery using standard stimulation and recording parameters.
      These potentials were obtained repetitively throughout the primary procedures and
      were performed again during a subsequent procedure that took place after the
      discovery of paraplegia. RESULTS: SEP and NMEP signals were preserved in both
      patients and no adverse events were identified during the initial procedures.
      Postoperatively, paraplegia was identified immediately upon recovery from
      anesthesia and preserved posterior column function was apparent on clinical exam.
      In the procedures following the discovery of paraplegia, SEP and NMEP signals
      remained comparable with signals elicited in the initial surgeries. CONCLUSIONS:
      Based on these cases and previously published experimental evidence, we conclude
      that while 'NMEPs' remain a useful second test of spinal cord function, they are
      not reliable indicators of motor tract function. An alternate term, such as
      'spinally-elicited peripheral nerve responses' should be used.

PMID- 11459685
TI  - New graphical method to measure silent periods evoked by transcranial magnetic
      stimulation.
AB  - OBJECTIVES: Manual methods of measuring duration of cortical silent periods (CSP)
      evoked by transcranial magnetic stimulation (TMS) depend upon subjective visual
      estimation of onset and offset. Because of this, the measurements are susceptible
      to poor rater reliability. We describe a graphical method to measure silent
      periods with greater precision. The statistical process underlying this new
      method is simple and particularly suited to signal detection in serially
      dependent data. METHODS: TMS-evoked silent periods were recorded in 13 healthy
      subjects. Two investigators subjectively measured silent period duration on each
      subject to estimate rater reliability. Using the graphical method, the mean and
      99.76% variation limits of pre-stimulus electromyogram (EMG) activity were
      computed. Each averaged trial was displayed and CSP onset and offset detected
      when post-stimulus EMG activity moved outside the 99.76% limits. RESULTS: Maximum
      variation in silent period duration was 21.8 ms between the two investigators'
      subjective measurements. Silent period duration measured with the graphical
      method closely approximated measurements obtained using the manual method. It was
      possible to automate the procedure. CONCLUSIONS: This graphical method allowed
      precise measurement of CSP duration, independent of subjective estimations of
      onset or offset points. Further studies are necessary to determine if this method
      can provide a framework for other physiologic measures.

PMID- 11459686
TI  - Changes in corticomotor representations induced by prolonged peripheral nerve
      stimulation in humans.
AB  - OBJECTIVE: Manipulation of afferent input can induce reorganization within the
      sensorimotor cortex which may have important functional consequences. Here we
      investigate whether prolonged peripheral nerve stimulation can induce
      reorganization within the human motor cortex. METHODS: Using transcranial
      magnetic stimulation, we mapped the scalp representation of the corticospinal
      projection to hand muscles in 8 normal subjects before and after 2h of
      simultaneous repetitive electrical stimulation of the ulnar and radial nerves at
      the wrist. Control mapping experiments were conducted in 6 subjects. RESULTS:
      Following nerve stimulation, larger motor-evoked potentials were evoked from more
      scalp sites. The induced changes were most apparent in first dorsal interosseous,
      but were also seen in other hand muscles. The increases in area of the
      representational maps were accompanied by changes in the location of the optimal
      site for evoking responses in first dorsal interosseous, and changes in the
      centres of gravity of the maps. CONCLUSIONS: Prolonged afferent stimulation
      induces an increase in excitability of the corticospinal projection. This is
      accompanied by a significant shift in the centre of gravity of the stimulated
      muscles which we propose is evidence of a non-uniform expansion in their cortical
      representation.

PMID- 11459687
TI  - The prolonged cortical silent period in patients with Huntington's disease.
AB  - OBJECTIVES: In a group of patients with Huntington's disease and age-matched
      controls, we studied the cortical silent period (SP) elicited by single
      transcranial magnetic stimulation (TMS) pulses. METHODS: We measured the area of
      the pre-stimulus electromyographic (EMG) activity, the area of the motor evoked
      potentials (MEPs) and the duration of the SP induced by stimuli delivered at an
      intensity of 150% of motor threshold with a round coil placed over the vertex. We
      determined the cortical SP by sampling only the 5 traces containing the shortest
      SPs and by collecting 10 consecutive unselected traces without selecting trials.
      RESULTS: Patients and controls had normal EMG background areas, and MEP latencies
      and areas. Whereas data measured from selected trials gave a normal duration of
      the SP (patients, 154+/-58 ms; controls, 166+/-22 ms), data from unselected
      trials yielded a significantly longer SP duration in patients than in controls
      (356+/-251 vs. 159+/-44 ms) and also a larger variance and range. CONCLUSIONS: We
      conclude that in Huntington's disease, an abnormal cortical SP is best sought by
      collecting unselected consecutive traces. We suggest that the prolonged SP in HD
      originates from a dysfunction of the mechanisms controlling the restart of
      voluntary movement after TMS.

PMID- 11459688
TI  - Somatosensory event-related potential and autonomic activity to varying pain
      reduction cognitive strategies in hypnosis.
AB  - OBJECTIVES: The issues of differential effects among cognitive strategies during
      hypnosis in the control of human pain are under active debate. This study, which
      employs measures of pain perception, electrocortical and autonomic responses, was
      aimed at determining these pain-related modulations. METHODS: Somatosensory event
      related potentials (SERPs) to noxious stimuli under an odd-ball paradigm were
      recorded at the frontal, temporal and parietal regions in 10 high, 9 mid, and 10
      low hypnotizable right-handed young women, at waking baseline, varying cognitive
      strategies (deep relaxation, dissociative imagery, focused analgesia) in hypnosis
      and placebo conditions. The phasic heart rate (HR) and skin conductance response
      were also recorded. The analysis was focused on the frequent standard trials of
      the odd-ball SERPs. Repeated measures analysis of variance was conducted to
      examine the experimental effects. RESULTS: Focused analgesia induced the largest
      reduction in pain rating, more in the high than low hypnotizable subjects. In
      high hypnotizable subjects, the N2 amplitude was greater over frontal and
      temporal scalp sites than over parietal and central sites, whereas in moderately
      and low hypnotizable subjects, N2 was greater over temporal sites than over
      frontal, parietal, and central sites. These subjects also displayed a larger N2
      peak over temporal sites during focused analgesia than in the other conditions.
      The P3 amplitude was smaller under deep relaxation, dissociative imagery and
      focused analgesia in the high hypnotizable subjects. For these subjects, the
      smallest P3 peaks were obtained for dissociated imagery and focused analgesia
      over frontal and temporal sites. In contrast, for the P3 peak, low hypnotizable
      subjects failed to show significant condition effects. In all of the subjects,
      the skin conductance and HR were smaller during hypnotic suggestions than in the
      waking state. CONCLUSIONS: The effect of pain modulation is limited to high
      hypnotizable subjects rather than low hypnotizable ones. Higher frontal-temporal
      N2 and smaller posterior parietal P3 may indicate active inhibitory processes
      during cognitive strategies in hypnotic analgesia. These inhibitory processes
      also regulate the autonomic activities in pain perception.

PMID- 11459689
TI  - EEG changes during word and figure categorization.
AB  - OBJECTIVE: To analyze whether the EEG changes observed during figure and word
      categorization are compatible with either the dual, the common amodal, or the
      alternative model (modality-specific codes for words and pictures, where meaning
      is represented for both in a higher-order amodal system) for semantic knowledge.
      METHODS: EEG was recorded during word and figure categorization of animals or non
      animals in a group of 28 children 8-10 years old. Computation of EEG sources in
      the frequency domain using variable resolution electrical tomography (VARETA) and
      their statistical evaluation by statistical parametric mapping were carried out.
      RESULTS: At all frequencies, there were significant changes between EEG segments
      prior to the presentation of the stimuli and EEG segments recorded after the
      stimuli. Post-segments showed more power from 1.56 to 7.02 Hz, and less power
      than pre-segments from 8 to 12.48 Hz. EEG changes were only observed in the word
      task at: 3.9 (left occipital), 4.68, 5.46, and 6.24 Hz (temporo-occipital
      regions). These changes may be associated with visual encoding of words.
      Frequencies 7.8 and 17.94 Hz increased in prefrontal, anterior cingulate, and
      anterior temporal regions only during figure categorization. The prefrontal
      region may be related to object working memory. Thus, these frequencies might be
      related to figure codification. No significant differences between tasks were
      observed at 3.12 and 7.02 Hz in very wide brain areas (all lobes except
      occipital), suggesting that the amodal semantic system storage could be the model
      compatible with figure and word categorization. CONCLUSIONS: Thus, our results
      support the modified amodal semantic hypothesis, which advocates that the
      meanings of both kinds of stimuli are represented in a conceptual memory that
      receives input from the logogen and iconogen systems.

PMID- 11459690
TI  - An integration of 40 Hz Gamma and phasic arousal: novelty and routinization
      processing in schizophrenia.
AB  - OBJECTIVES: Frontal and lateralized schizophrenia disturbances were examined in
      terms of arousal-modulated changes in 40 Hz Gamma activity. METHODS: Forty
      patients with schizophrenia and 40 age- and gender-matched controls were studied
      in a conventional auditory ERP oddball paradigm. We investigated sub-averaged
      Gamma activity based upon a simultaneous measure of electrodemal skin conductance
      response (phasic arousal) to differentiate novelty (large responses) from
      routinization (small or no responses). Both early Gamma (Gamma 1) and later
      induced Gamma (Gamma 2) activities were examined. RESULTS: Patients with
      schizophrenia (compared with controls) had significantly reduced Gamma 1
      amplitude in the right hemisphere for novelty processing and delayed Gamma 2
      latency in the left hemisphere for both novelty and routinization. Overall,
      reduced Gamma 1 amplitude in patients with schizophrenia was also evident.
      CONCLUSIONS: These findings indicate that the normal laterality of Gamma activity
      is specifically disturbed in schizophrenia in response to novel, but not routine
      (familiar) stimuli. The distinct pattern of findings suggests a dysregulation of
      activation across left and right hemispheres during initial attention and
      preparatory phases of information processing, in particular, in patients with
      schizophrenia.

PMID- 11459691
TI  - CNS recovery from cocaine, cocaine and alcohol, or opioid dependence: a P300
      study.
AB  - OBJECTIVES: The goal of the present study was to evaluate the relative effects of
      cocaine, cocaine and alcohol, or opioid dependence on P300 event-related
      potentials (ERPs). In addition, the effects of selected premorbid and comorbid
      factors were examined. METHODS: P300 ERPs were recorded from 72 residential
      treatment program patients, characterized by a history of either cocaine (n=25),
      or cocaine and alcohol (n=18), or opioid (n=29) dependence, and 14 non-drug
      dependent community volunteers. The 86 subjects completed a visual continuous
      performance test formed by a series of 150 presentations of individual consonant
      letters. They were asked to press a key whenever a letter was presented twice in
      succession. RESULTS: Analyses of P300 ERPs obtained on target trials revealed a
      similar amplitude decrement in all the patient groups. Further analyses of P300
      activity in the 3 drug-dependent patient groups revealed a negative correlation
      between P300 amplitude and the number of DSM-IIIR childhood conduct disorder
      criterion behaviors as well as a positive correlation between P300 amplitude and
      the duration of drug abstinence. CONCLUSIONS: P300 amplitude in drug-dependent
      patients is influenced by a complex interaction between CNS pathology that
      predates, and probably promotes, the onset of drug dependence and CNS pathology
      that resolves during the process of recovery from drug dependence.

PMID- 11459692
TI  - Specific somatosensory processing in somatosensory area 3b for human thumb: a
      neuromagnetic study.
AB  - OBJECTIVES: We examined the relation between somatosensory N20m primary responses
      and high-frequency oscillations (HFOs) after thumb and middle finger stimulation.
      METHODS: Somatosensory evoked fields (SEFs) from 12 subjects were measured
      following electric stimulation of the thumb and middle finger. SEFs were recorded
      with a wide bandpass (3-2000 Hz) and then N20m and HFOs were separated by
      subsequent 3-300 and 300-900 Hz bandpass filtering. RESULTS: The N20m peak-to
      peak amplitude did not differ significantly between thumb and middle finger SEFs.
      In contrast, HFOs had a significantly larger number of peaks and were higher in
      the maximum amplitude and the total amplitude after thumb stimulation than after
      middle finger stimulation. CONCLUSIONS: Our present data demonstrate a different
      relation between N20m and HFOs after thumb and middle finger stimulation. In view
      of the fact that the human thumb has uniquely evolved functionally and
      morphologically, the somatosensory information from the thumb will be processed
      differently for a fine motor control. We speculate that HFOs are generated by
      inhibitory interneurons in layer 4 in area 3b. Thus, enhanced activity of
      interneurons reflected by high amplitude HFOs exerts stronger inhibition on
      downstream pyramidal cells in area 3b for thumb stimulation.

PMID- 11459693
TI  - Olfactory event-related potentials in patients with brain tumors.
AB  - OBJECTIVE: The aim of the study was to determine how odor processing is altered
      in patients with unilateral supratentorial brain tumors. METHODS: Olfactory event
      related potentials (OERPs) were evaluated in 10 patients with unilateral brain
      tumors of the frontal or temporal lobe in response to linalool and allylcaproate.
      Both odors were presented monorhinally by a constant-flow olfactometer. In
      addition, 20 healthy subjects were examined. While sniffing, the subjects were
      asked to discriminate the two odors. EEG was recorded from 7 electrode positions
      (Fz, Cz, Pz, F3/4, P3/4). Amplitudes and latencies of 3 peaks (N1, P2, P3) were
      measured. To control for effects of modality-non-specific alterations on the
      olfactory components acoustic event-related potentials (AERPs) were registered by
      use of an oddball paradigm. RESULTS: Patients with right-sided lesions showed
      distinct deficits in the discrimination task after stimulation of the right and
      left nostril. In contrast, patients with left-sided lesions only had an
      attenuation of correct reactions after left-sided stimulation. In the OERPs,
      patients with right-sided lesions showed P2- and P3-components with decreased
      amplitudes at parietal electrode positions. These alterations appeared after ipsi
      and contralateral stimulation. Patients with left-sided lesions showed a
      significant effect of the side of stimulation. Their OERP-amplitudes were
      decreased after left-sided stimulation but not after right-sided stimulation.
      After right-sided olfactory stimulation a correlation between the olfactory and
      the acoustic ERP was seen in patients with right-sided lesions. CONCLUSIONS:
      Olfactory performance of the participating patients was markedly reduced.
      Patients with right-sided lesions showed bilateral impairment, which would
      support the importance of the right hemisphere in olfaction. The alteration of
      the topographic distribution of P2- and P3-amplitudes in patients with right
      sided lesions might reflect an impairment of early and late olfactory processing
      steps.

PMID- 11459694
TI  - Brain-stem compression in vertebrobasilar dolichoectasia. A multimodal
      electrophysiological study.
AB  - OBJECTIVE: To evaluate the effects of mechanical compression of the brain-stem in
      patients with vertebrobasilar dolichoectasia (VBD). METHODS: In the framework of
      a prospective, observational study that collected clinical and laboratory data in
      patients with VBD, we studied 20 patients with compression of the brain-stem due
      to ectatic, tortuous basilar or vertebral arteries. Patients with cerebral
      lesions other than small lacunae in the white matter of the cerebral hemispheres
      were excluded from the study. Patients underwent vestibular and auditory function
      testing, including brain-stem auditory evoked potentials (BAEPs), blink reflex
      (BR), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs).
      RESULTS: Almost all of the patients complained of auditory or vestibular symptoms
      and none had symptoms or signs of impairment of long tracts or the facial and
      trigeminal nerves. The most consistent findings were BR abnormalities with
      prolongation of ipsilateral R1 latency in cases of compression of the pons
      (10/16) and prolongation of the R2 and R2c latencies with compression of the
      medulla oblongata (5/15). Subclinical impairment of corticospinal pathways was
      found in 13 out of 25 instances of compression, and this was more frequent with
      compression of the pons. Abnormal BAEPs or SEPs were less frequently encountered,
      and only in cases with compression of the pons. CONCLUSIONS: Neurovascular
      compression of the brain-stem, even with severe distortion, is seldom associated
      with overt clinical signs, whereas subclinical dysfunctions are relatively
      frequent. The central pathways of the BR and the corticospinal pathways are more
      susceptible to compression than acoustic and sensory pathways. BR, MEP and BAEP
      data provide a functional evaluation of the brain-stem and some cranial nerves,
      which is lacking in imaging studies. Functional investigations may be useful in
      the long-term management of these patients, since VBD may be progressive and
      surgical correction may be required at some stage.

PMID- 11459695
TI  - Internight reliability and benchmark values for computer analyses of non-rapid
      eye movement (NREM) and REM EEG in normal young adult and elderly subjects.
AB  - OBJECTIVE: To determine the reliability of computer measured non-rapid eye
      movement (NREM) and REM frequency bands in the 0.3-45 Hz range and to provide
      benchmark data for these measures in young normal (YN) and elderly normal (EN)
      subjects (Ss). METHODS: Sleep EEG was recorded in 19 YN and 19 EN Ss on 4 non
      consecutive baseline nights and simultaneously quantified as fast Fourier
      transform (FFT) power and 3 zero-cross period-amplitude (PA) measures: integrated
      amplitude, time in band and average wave amplitude. RESULTS: The shapes of both
      the FFT and PA spectra differed among Ss but were highly consistent within
      individuals. Inter-night reliability of the separate frequency bands was
      correspondingly high. Despite substantial age effects, the reliability of
      computer-measured sleep EEG in the elderly equaled that of the YN Ss. Within both
      the YN and EN groups, the shapes of the NREM and REM spectral curves differed
      significantly. The NREM and REM also differed significantly in the two age
      groups. CONCLUSIONS: Computer-measured sleep EEG is highly reliable across non
      consecutive nights in both young and elderly normal Ss. The trait-like stability
      of these measures suggests they are genetically determined. This possibility is
      supported by twin study data that show strong heritability for FFT-measured
      waking EEG. The different shapes of NREM and REM spectra add further evidence
      that these are fundamentally different states of brain organization. The age
      differences in spectral shape, along with PA data for wave incidence, demonstrate
      that age effects on sleep EEG are not caused by changes in skull impedance or
      other non-cerebral factors.

PMID- 11459696
TI  - Automatic alignment of EEG/MEG and MRI data sets.
AB  - OBJECTIVES: We developed a new technique of fully automatic alignment of brain
      data acquired with scalp sensors (e.g. electroencephalography/evoked potential
      (EP) electrodes, magnetoencephalography sensors) with a magnetic resonance
      imaging (MRI) volume of the head. METHODS: The method uses geometrical features
      (two sets of head points: digitized from the subject and extracted from MRI) to
      guide the alignment. It combines matching on 3 dimensional (3D) geometrical
      moments that perform the initial alignment, and 3D distance-based alignment that
      provides the final tuning. To reduce errors of the initial guessed computation
      resulting from digitization of the head surface points we introduced weights to
      compute geometrical moments, and a procedure to remove outliers to eliminate
      incorrectly digitized points. RESULTS: The method was tested on simulated (Monte
      Carlo trials) and on real data sets. The simulations demonstrated that for the
      number of test points within the range of 0.1-1% of the total number of head
      surface points and for the digitization error in the range of -2-2 mm the average
      map error was between 0.7 and 2.1 mm. The average distance error was less than 1
      mm. Tests on real data gave the average distance error between 2.1 and 2.5 mm.
      CONCLUSIONS: The developed technique is fast, robust and comfortable for the
      patient and for medical personnel. It registers scalp sensor positions with MRI
      head volume with accuracy that is satisfactory for localization of biological
      processes examined with a commonly used number of scalp sensors (32, 64, or 128).

PMID- 11459697
TI  - The development of a software program for analyzing skin conductance changes in
      preterm infants.
AB  - OBJECTIVES: Changes in palmar and plantar skin conductance (SC) are due to
      outgoing bursts in the postganglionic efferent sympathetic cholinergic fibres,
      which respond to changes in the central arousal state. An apparatus that measures
      SC by applying an alternating voltage is sensitive enough to measure SC changes
      in preterm infants. The purpose of this study was to develop a software program
      for analyzing SC in premature infants. METHODS: The software program was designed
      to calculate the number and mean amplitude of the waves and the mean SC changes
      during a given period. Different pre-set values for minimum amplitude, maximum
      slope and minimum width of the waves were used in the program and the results
      were compared with manually counted waves. RESULTS: For SC waves, the optimal
      minimum amplitude was found to be 0.015 microS, the maximum slope of the waves
      could, with the same result, be 1, 2 or 5 microS/s and the optimal width of the
      waves was found to be unlimited. CONCLUSIONS: SC in preterm infants is easily
      analyzed by this software program.

PMID- 11459698
TI  - [Chart no 45 - WRN (RCQL3)].

PMID- 11459699
TI  - [The RB gene family and control of the cell cycle].

PMID- 11459700
TI  - [New insight into MyoD regulation: involvement in rhabdomyosarcoma pathway?].
AB  - The transcription factor MyoD, member of the myogenic regulators family, induces
      differentiation in precursor cells by its ability to arrest cell proliferation
      and to activate muscle specific genes. MyoD plays a key role in the antagonism
      between proliferation and differentiation. The withdrawal from the cell cycle and
      the activation of muscle differentiation are related to the level of MyoD
      protein. The cyclin E-cdk2 complex, one of the key regulators of the G1/S
      transition is directly implicated in the degradation of MyoD by the ubiquitin
      proteasome pathway, leading the myoblasts to proliferate. The display of this
      control in normal myoblasts suggests that its deficiency in the muscle stem cells
      could lead to the formation of rhabdomyosarcomas which have lost both the control
      of cell proliferation and the transcriptional activity of MyoD.

PMID- 11459701
TI  - ["Micrometastases": the pathologist's point of view].
AB  - The development of cancer screening has led to the discovery of smaller tumours
      and less frequent dissemination to lymph nodes and organs that requires special
      techniques for detection. Numerous papers on micrometastases reflect a
      considerable amount of work devoted to detection methods, technical problems and
      the prognostic value of these lesions. Apart from cytological techniques, the
      pathologist can rely on two methods for the detection of micrometastases: serial
      slicing of paraffin-embedded blocks and immunohistochemistry. When these methods
      are combined, the detection rate is similar to that of biological methods and can
      attain levels as high as 60% for the sentinel node with the added vantage of
      being able to visualise cells. Despite an impressive body of studies, major
      disparities are found in detection rates and the prognostic value of
      micrometastases is not firmly established. In order to facilitate comparisons and
      analyses, it is essential to adopt a common terminology with precise definitions.
      The UICC advocates the use of the term micrometastasis which denotes a metastasis
      smaller than or equal to 2 mm in size. The potential aggressiveness of
      micrometastases is dependent on other poorly explored parameters such as the
      number of cells detected in the bone marrow or lymph node and the location of
      micrometastases. The new pTNM classification takes into account this latter
      parameter and distinguishes two categories of micrometastases: "isolated tumor
      cells" located in the lumen of vessels or sinuses and "micrometastasis" which has
      already invaded an organ. This classification warrants further analysis to
      determine the prognostic value of these categories. The next challenging problem
      consists in determining the key biological properties that account for distant
      dissemination.

PMID- 11459702
TI  - [Detection of micrometastases and circulating tumour cells using molecular
      biology technics in solid tumours].
AB  - The extension of a cancer is a major prognostic factor which determines the
      therapeutic strategy. The occurrence of metastatic relapses in patients with
      initially localized tumours, despite a good local control, gives evidence for the
      possibility of spreading of occult tumour cells. The recent improvements of
      immunohistochemistry and molecular biology methods enable to detect tumour cells
      in various sites such as lymph nodes, bone marrow and blood with a considerably
      increased sensitivity as compared to conventional approaches. The markers used to
      detect tumour cells by PCR or RT-PCR can be either "tissue-specific" or "tumour
      specific". The drawback of the first group of markers is linked to the
      observation that tissue-specificity is frequently a relative concept leading to a
      high rate of false positives. Tumour-specific markers include gene fusions
      observed in various sarcomas, point mutations and presence of viral genomes in
      tumour cells. They are available and can be easily monitored in only a limited
      set of cancers. This review focuses on the molecular biology approaches which are
      used to detect occult tumour cells and on their clinical applications. The large
      number of studies which have been published in that field show that such a
      detection can be performed in a variety of target sites. However, results of
      studies performed on larger series of patients together with a better
      standardization of technics are necessary before they can be used for individual
      staging of patients.

PMID- 11459703
TI  - [Residual disease: the hematologist's point of view].
AB  - Minimal residual disease (MRD) can be easily studied in hematological
      malignancies by analyses of various fusion transcripts or tumor-specific
      immunoglobulin heavy-chain or T-cell receptor rearrangements as markers of
      disease. Correlation between MRD and prognosis has been extensively investigated
      mostly in acute leukemia and chronic myeloid leukemia. Quantitative aspect seems
      an essential criterion but the current absence of standardization makes difficult
      clinical decision according to MRD results. Development of real time quantitative
      PCR techniques would probably overcome these limitations. Only follicular non
      Hodgkin's lymphomas are currently routinely analyzed using BCL2-JH PCR but
      signification of results obtained in complete remission remains uncertain.
      Analyses of tumor-specific immunoglobulin heavy-chain or T-cell receptor
      rearrangements allow physiological study and evaluation of bone marrow purgin
      system efficacy but are of limited interest in current clinical practice.

PMID- 11459704
TI  - [Micrometastases in pediatric oncology].
AB  - Metastatic relapse in children with solid tumors is mainly caused by systemic
      pretreatment dissemination of occult tumor cells. Therefore the initial detection
      of undetected metastases could have a clinical impact on the prognosis (i.e. new
      initial staging) and therapy for children with cancer. At later stage it is
      useful to determine the presence and change in the number of residual malignant
      cells in order to adjust and/or select adjuvant therapies and techniques (i.e.
      autologous bone marrow transplantation, leukapheresis.). Over the past decade,
      sensitive immunocytochemical and molecular assays have been developed which
      permit the identification of disseminated cancer cell. Actually tumor cell
      contamination can be detected in bone marrow or in peripheral blood of children
      with following cancers: neuroblastoma, Ewing tumor, alveolar rhabdomyosarcoma,
      PNETs. In this review, focus is on the recent technical achievements in the
      detection of occult cancer cells in bone marrow and in blood and a discussion of
      their usefulness for clinical trials.

PMID- 11459705
TI  - [Li-Fraumeni syndrome: update, new data and guidelines for clinical management].
AB  - The Li-Fraumeni syndrome (LFS) is an inherited form of cancer, affecting children
      and young adults, and characterized by a wide spectrum of tumors, including soft
      tissue and bone sarcomas, brain tumours, adenocortical tumours and premenopausal
      breast cancers. In most of the families, LFS results from germline mutations of
      the tumor suppressor TP53 gene encoding a transcriptional factor able to regulate
      cell cycle and apoptosis when DNA damage occurs. Recently, germline mutations of
      hCHK2 encoding a kinase, regulating cell cycle via Cdc25C and TP53, were
      identified in affected families. The LFS working group recommendations are the
      following: (i) positive testing (screening for a germline TP53 mutation in a
      patient with a tumor) can be offered both to children and adults in the context
      of genetic counseling associated to psychological support, to confirm the
      diagnosis of LFS on a molecular basis. This will allow to offer to the patient a
      regular clinical review in order to avoid a delay to the diagnosis of another
      tumor; (ii) the 3 indications for positive testing are: a proband with a tumor
      belonging to the narrow LFS spectrum and developed before age 36 and, at least,
      first- or second-degree relative with a LFS spectrum tumor, before age 46, or a
      patient with multiple primary tumors, 2 of which belonging to the narrow LFS
      spectrum, the first being developed before 36 or a child with an adenocortical
      tumour; (iii) presymptomatic testing must be restricted to adults; (iv) the young
      age of onset of the LFS tumors the prognosis of some tumors, the impossibility to
      ensure an efficient early detection and the risk for mutation carriers to develop
      multiple primary tumors justify that prenatal diagnosis might be considered in
      affected families.

PMID- 11459706
TI  - [Consensus conference: Preventing the risk of Aspergillus infection in
      immunocompromised patients].

PMID- 11459707
TI  - [Standards, Options and Recommendations: a multidisciplinary program to promote
      evidence-based oncology].

PMID- 11459708
TI  - [Standards, Options and Recommendations for home parenteral or enteral nutrition
      in adult cancer patients].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of the French Cancer Centres
      (FNCLCC), the 20 French Cancer Centres and specialists from French Public
      Universities, General Hospitals and Private Clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and outcome for cancer patients. The methodology is based on literature review
      and critical appraisal by a multidisciplinary group of experts, with feedback
      from specialists in cancer care delivery. OBJECTIVES: To develop clinical
      practice guidelines according to the definitions of the Standards, Options and
      Recommendations project for home parenteral or enteral nutrition in adult cancer
      patients. METHODS: Data were identified by searching Medline, Cancerlit, web
      sites and using the personal reference lists of members of the expert groups.
      Once the guidelines were defined, the document was submitted for review to 72
      independent reviewers. RESULTS: The main recommendations for home parenteral or
      enteral nutrition in adult cancer patients are: 1) Home parenteral or enteral
      nutrition concerns cancer patients with malnutrition or with
      inadequate/impossible oral intake, during therapy of because of therapeutic after
      effects (standard). Same indications apply for home and hospital artificial
      nutrition (standard). 2) Patients need a multidisciplinary follow-up
      (oncologists, nutritionists, and pain specialists), and this follow-up will make
      treatment adaptations according to the nutritional status possible
      (recommendation, expert agreement). An active participation of patients and/or
      their family circle is very important (standard). 3) The benefit of home
      parenteral or enteral nutrition on the quality of life of terminally ill patients
      (vs. hydration) has not been demonstrated. When life expectancy is below 3
      months, and the Karnofsky index below 50, the drawbacks of home artificial
      nutrition are more important than its advantages. In this case, home parenteral
      or enteral nutrition is not recommended (recommendation, expert agreement). 4)
      Prospective clinical trials are recommended to evaluate the impact of home
      nutrition on quality of life in cancer patients (expert agreement). 5) The use of
      educational booklets that mention the telephone number of a referent health care
      and what to do when a problem happens (e.g. fever on home parenteral nutrition)
      is recommended (expert agreement). In France, patients should be referred to
      authorized home parenteral nutrition centres (recommendation, expert agreement).

PMID- 11459709
TI  - [Cancers of unknown origin: 311 cases].
AB  - Carcinoma of unknown primary site has been defined as a metastatic disease
      without known primary site (upon clinical, radiological or endoscopic
      examination) at the initial therapeutic decision. The incidence of such
      carcinomas is between 1.6 and 15% of all adult's tumors. The goals of this
      retrospective and monocentric study were 1) the incidence of these carcinoma; 2)
      the utility to identify the primary site; 3) the efficacy of treatment in terms
      of survival; and 4) the prognostic factors to optimize strategic choices. Between
      January 1980 to December 1995, 311 cases were identified; this represents 1.6% of
      all cases treated in our center. Histological analyses of metastases revealed
      adenocarcinoma: 164 cases (92 males, 72 females; 29 well differentiated, 11
      poorly differentiated and 41 undifferentiated); squamous cell carcinoma: 90 cases
      (78 males, 12 females); undifferentiated carcinoma: 27 cases (21 males, 6
      females); neuro-endocrine tumor: 10 cases; and others: 20 cases. Median age was
      61.1 years (30-94). Half of the patients had a PS between 0 and 1. The carcinoma
      was revealed by only one site of metastases in 35% of the cases (lymph node
      72.9%, bone 35.5%, liver 19.4% and lung 16.5%). The primary carcinoma was found
      in only 6% of the cases. Median survival of all patients was only 9 months.
      Multivariate analyses by the Cox method show four positive prognostic factors:
      sex (female), performance status (PS < 2), histological analyses (squamous cell
      carcinoma), only one site of metastases.

PMID- 11459710
TI  - [Notification of nosocomial infections in cancerology].

PMID- 11459713
TI  - The epidemiology of pain in elderly people.
AB  - Acute pain probably occurs at much the same rate across all age groups. On the
      other hand, self-report of chronic pain seems to increase up to, but not beyond,
      the seventh decade of life. Chronic pain in older people is more often
      experienced in major joints, the back, legs and feet, whereas visceral pain and
      headache are reported less often. There is a divergence between an increasing
      load of pain-associated disease and a plateau of chronic pain complaint in old
      age that probably reflects impairment in the nociceptive function of the nervous
      system. However, the contribution of social, behavioral, cognitive, and affective
      dimensions of the pain experience to this divergence between disease and pain
      have not been fully evaluated. Most of the answers to these and other questions
      require longitudinal studies with pain as the predominant focus of attention
      rather than addressing the symptom of pain as an ancillary measure relevant to
      other aspects of aging.

PMID- 11459714
TI  - Age-related differences in pain perception and report.
AB  - The clinical and laboratory-based evidence for age-related differences in pain
      perception and report are reviewed. Most clinical studies suggest a relative
      decrease in the frequency and intensity of pain symptoms associated with
      myocardial complaints, visceral infections, musculoskeletal conditions, and
      postoperative and malignant pain problems in adults of advanced age. The findings
      from experimentally controlled laboratory investigations are more equivocal and
      vary according to the type and intensity of noxious stimulation. Nonetheless,
      such studies also provide some additional support for the notion of an age
      related decrease in pain perception and report. Evidence has not determined
      whether the observed changes are caused by the aging process or reflect other age
      associated effects, including an increased presence of comorbid disease,
      biocultural cohort effects, or altered psychosocial influences.

PMID- 11459716
TI  - Opioid analgesic drugs in older people.
AB  - Many studies have corroborated the finding that older patients in all clinical
      settings are at risk for insufficient assessment and inadequate management of
      pain. Opioid analgesics can greatly improve the quality of life and functional
      capacities of older patients with moderate to severe pain that is not responsive
      to other therapies; however, these agents are underused in this population. To
      improve the care of older patients, clinicians must develop expertise in
      appropriate indications, pharmacologic properties, drug-disease and drug-drug
      interactions, and ongoing monitoring of opioid analgesic therapy.

PMID- 11459715
TI  - Assessment and measurement of pain in older adults.
AB  - Although the empiric base is still limited when providing clear directions for
      pain assessment and management in older adults, it is possible to identify
      recommendations for guiding practice based on consensus and a developing
      scientific base to support best practice activities. A brief overview of the
      epidemiology and consequences of pain is offered, followed by a summary of issues
      and approaches relevant to pain assessment in older adults. Cohort-specific
      recommendations for comprehensive pain assessment and measurement based on
      current evidence are then addressed, including strategies for assessment of pain
      in cognitively impaired older adults.

PMID- 11459717
TI  - Cox-2 inhibitors and other nonsteroidal anti-inflammatory drugs in the treatment
      of pain in the elderly.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly
      prescribed therapies for acute and chronic pain in the elderly. NSAIDs are
      effective in treating many disorders, but their use often is limited by
      toxicities, especially gastrointestinal and renal toxicity. COX-2 inhibitors are
      a major therapeutic advance, providing the analgesic and anti-inflammatory
      activity of NSAIDs, with a significant improvement in gastrointestinal safety.
      These new agents may be ideal therapies for older patients at risk for NSAID
      related gastrointestinal toxicity.

PMID- 11459718
TI  - Cognitive-behavioral therapy for chronic pain in the elderly.
AB  - Cognitive-behavioral therapy has become a common nonpharmacologic treatment
      option for individuals experiencing chronic nonmalignant pain. This article
      begins with an overview of the cognitive-behavioral perspective on pain and pain
      management. The second section discusses relevant developmental issues and
      suggests refinements to cognitive-behavioral therapy for the elderly, followed by
      a case example describing the implementation of cognitive-behavioral therapy for
      an elderly gentleman in an ambulatory care setting. The details of assessment,
      treatment conceptualization and planning, intervention, and follow-up are
      explored in this context. This article concludes with suggestions for future
      refinements in the application of this approach in the management of chronic pain
      in the elderly.

PMID- 11459719
TI  - Physical therapy and exercise in pain management.
AB  - Physical therapy and exercise are fundamental to the interdisciplinary approach
      to pain management in the elderly. Physical modalities used in combination with
      exercise provide pain relief and help to prevent future pathology and physiologic
      changes in the elderly that often result in significant pain syndromes. This
      article provides an overview of effective modalities for pathology prevention,
      treatment of pain, and restoration of function that are the basis for pain
      management in geriatric patients.

PMID- 11459720
TI  - Regulatory issues in pain management.
AB  - Patients commonly are left to suffer from pain that affects their daily lives.
      The prevalence of undertreated, moderate to severe pain is a public health
      problem in many countries, including the United States. In many cases, opioids
      should be the mainstay for the treatment of this level of pain, but they often
      are not used or are underdosed. One of the reasons for this underuse most cited
      by health care professionals is their fear of sanctions by their governing
      boards, law enforcement, or their misunderstanding of the laws and regulations
      governing the use of these controlled substances. This article reviews some of
      the relevant issues of the regulation of controlled substances, updates the
      reader about the laws, and provides guidance to practitioners about the
      appropriate use of controlled substances, especially opioids, to manage pain.

PMID- 11459721
TI  - Principles of perioperative pain management in older adults.
AB  - The consequences of poor planning for pain management during surgery of geriatric
      patients not only affect the immediate well-being of the patient but also have
      terrible socioeconomic implications. Delays in rehabilitation, increases in
      hospital lengths of stay, and increased comorbidity can be expected if
      interventions for pain management are either inadequate or excessive without
      appropriate monitoring. During surgery, seniors are likely to suffer from acute
      and chronic pain that must be addressed aggressively in the postoperative period
      to ensure a rapid functional recovery. New pain scales have been developed with
      seniors in mind, and greater testing of older scales in elderly populations have
      helped to identify measures of pain more suited to frail seniors. This article is
      designed to help clinicians to strategically implement optimal pain management
      principles and techniques and, thus, help to fulfill the obligation to relieve
      pain and suffering in patients in the perioperative period, which will ensure the
      greatest chance of recovery to optimal independence for patients.

PMID- 11459722
TI  - Pain in the nursing home.
AB  - The treatment of pain in the nursing home setting continues to present several
      unique and challenging problems. Increasingly, studies are focusing on the large
      number of elderly with important pain problems in long-term care. The inclusion
      of pain as an area of clinical focus in the Minimum Data Set has fueled interest
      in this problem and will provide solid data for future study. Researchers are
      attempting to establish reliable and valid data using standardized assessment
      tools previously validated in younger adults and are attempting use of
      traditional and cutting-edge assessment tools in cognitively impaired patients.
      Assessment is being linked to innovative interventions in noncommunicative,
      cognitively impaired residents using primary care nurses who best know these
      patients to decipher "normal" from "abnormal" behavior. The application of
      available pharmacologic interventions are more challenging because of the higher
      incidence of side effects in the elderly; part of this problem is the result of
      the decreased hepatic metabolism and renal clearance present in older patients.
      The nursing home environment has limited resources that can create logistical
      concerns in terms of diagnosis and treatment but also can positively limit overly
      invasive modalities. This article explores these issues and offers suggestions
      for the appropriate assessment and management of pain in long-term care
      residents.

PMID- 11459723
TI  - Pain observed: the experience of pain from the family caregiver's perspective.
AB  - Researchers have studied pain and family caregiving across ages and various
      diseases. They have begun to explore barriers to family caregivers' roles in pain
      management and to assess family caregivers' knowledge and beliefs about pain. One
      consistent finding is that the fears and the inappropriate knowledge and beliefs
      of family caregivers often are worse than those of patients. This article
      provides a brief description of the program of research performed by the author
      and colleagues over the past 16 years related to pain management at home and to
      the role of family caregivers.

PMID- 11459724
TI  - Sentinel node localization: do or dye alone?

PMID- 11459725
TI  - Lung cancer screening.
AB  - Prior attempts to screen for lung cancer using chest radiography and sputum
      cytology have proved unsuccessful. Recent reports have investigated the role of
      spiral CT in early lung cancer detection and have suggested that screening would
      be of value. Prior to the introduction of a national lung cancer screening
      programme, it would be essential to demonstrate that this would reduce mortality
      and would be cost effective.

PMID- 11459726
TI  - Role of radionuclide imaging in hyperthyroid patients with no clinical suspicion
      of nodules.
AB  - The purpose of the study was to assess the role of radionuclide imaging of
      hyperthyroid patients with no suspicion of nodules. (99)Tc(m) radionuclide scans
      performed on all 190 patients referred over a 2-year period with symptoms and
      thyroid function tests compatible with thyrotoxicosis were retrospectively
      reviewed. 73% of patients were referred by a hospital clinician and 27% were
      referred direct from the general practitioner. Referral letters and, where
      applicable, the clinical notes were reviewed and patients with suspected thyroid
      nodules were excluded. The results of (99)Tc(m) thyroid scans of the 190 patients
      (age range 23-93 years, mean 48 years) were reviewed. 152 (80%) patients had
      Graves' disease, 10 (5.3%) had Graves' disease with nodules, 6 (3.2%) had Graves'
      disease with non-functioning nodules, 5 (2.6%) had viral thyroiditis, 5 (2.6%)
      had autonomously functioning nodules and 12 (6.3%) were normal studies.
      Therefore, 20% of patients had a diagnosis other than solely Graves' disease.
      These diagnoses are important with respect to clinical management. In conclusion,
      routine radionuclide imaging is worthwhile, as a significant proportion of
      patients with clinical "Graves' disease" in this study would have received
      incorrect treatment without the result of this scan.

PMID- 11459727
TI  - CT differentiation of pneumonic-type bronchioloalveolar cell carcinoma and
      infectious pneumonia.
AB  - The objective was to analyse the potential of CT to distinguish pneumonic-type
      bronchioloalveolar cell carcinoma (BAC) from infectious pneumonia. The study
      consisted of 21 patients with pathologically proven BAC and 30 patients with
      infectious pneumonia. Both groups of patients had patchy or diffuse consolidation
      of more than half the area of a lobe or lobes on CT. CT findings in these two
      groups were compared with regard to morphological appearance, including CT
      angiogram, air bronchogram, mucous bronchogram, contrast enhancement pattern,
      pseudocavitation, cavity with air-fluid level, location, satellite lesion, ground
      glass opacity and bulging of the interlobar fissure. Air-filled bronchi were
      morphologically analysed as dilatation, stretching, sweeping, widening of the
      branching angle, squeezing and crowding. Lymphadenopathy and pleural effusion
      were also analysed. CT findings favouring the diagnosis of BAC included an air
      filled bronchus within the consolidation with stretching, squeezing, sweeping,
      widening of the branching angle and bulging of the interlobar fissure (p<0.05).
      It is concluded that CT may be helpful in differentiating pneumonic-type BAC from
      infectious pneumonia if the air-filled bronchus within the consolidation shows
      stretching, squeezing, widening of the branching angle or bulging of the
      interlobar fissure.

PMID- 11459728
TI  - Renal arteriography using gadolinium enhanced 3D MR angiography--clinical
      experience with the technique, its limitations and pitfalls.
AB  - Gadolinium enhanced 3D MR angiography (MRA) is becoming a widely accepted
      technique for imaging the vascular system. We set out to evaluate its accuracy
      and reliability in visualization of renal arteries in the clinical setting.
      Gadolinium enhanced MRA was performed in 15 potential live renal donors and 26
      patients suspected of having renal artery stenosis who were referred for digital
      subtraction angiography (DSA). MRA was performed on a 1.5 T MR scanner in a
      single breath hold. Images from each study were prospectively analysed for
      demonstration of number of main and accessory renal arteries and degree of renal
      artery stenosis in a double blind fashion. All the main and accessory arteries
      were visualized on MRA in the renal donor group, but in one case a branch was not
      identified owing to breathing artefact. In one case, an extrarenal vascular
      anomaly was not demonstrated on MRA. In the renal artery stenosis group,
      sensitivity, specificity and negative predictive values of 96%, 93% and 96% were
      obtained for clinically significant stenosis (>50%). Gadolinium enhanced MRA
      proved to be a useful technique in demonstration of renal arterial anatomy and
      grading of renal artery stenosis. However, we encountered some pitfalls and
      limitations of the technique during the process. It is important to be aware of
      these before accepting it as the sole technique in clinical practice.

PMID- 11459729
TI  - Re-irradiation for prophylaxis of heterotopic ossification after hip surgery.
AB  - Heterotopic ossification (HO) may occur after total hip arthroplasty, but
      fortunately most patients are asymptomatic. Rick factors for HO include previous
      HO, hypertrophic osteoarthritis, diffuse idiopathic skeletal hyperostosis,
      ankylosing spondylitis, Paget's disease and post-traumatic arthritis. Both pre
      operative and post-operative radiotherapy are effective in the prevention of HO
      in 85-95% of high-risk patients treated. In the few patients who needed re
      operation for a variety of reasons, we found that re-irradiation is possible and
      safe. These case reports present our experience with single dose re-irradiation
      of the hip in an attempt to prevent post-operative HO.

PMID- 11459730
TI  - 100 years of observation on British radiologists: mortality from cancer and other
      causes 1897-1997.
AB  - Radiologists and radiotherapists were one of the earliest occupational groups to
      be exposed to ionizing radiation. Their patterns of mortality provide information
      on the long-term effects of fractionated external radiation exposure. British
      radiologists who registered with a radiological society between 1897 and 1979
      have now been followed-up until 1 January 1997, and the mortality experience
      examined among those who registered with a society after 1920, when the first
      radiological protection recommendations were published. The observed number of
      cancer deaths in those who registered after 1920 was similar to that expected
      from death rates for all medical practitioners combined (SMR=1.04; 95% CI 0.89
      1.21). However, there was evidence of an increasing trend in risk of cancer
      mortality with time since first registration with a radiological society
      (p=0.002), such that in those registered for more than 40 years there was a 41%
      excess risk of cancer mortality (SMR=1.41; 95% CI 1.03-1.90). This is probably a
      long-term effect of radiation exposure in those who first registered during 1921
      1935 and 1936-1954. There was no evidence of an increase in cancer mortality
      among radiologists who first registered after 1954, in whom radiation exposures
      are likely to have been lower. Non-cancer causes of death were also examined in
      more detail than has been reported previously. There was no evidence of an effect
      of radiation on diseases other than cancer even in the earliest radiologists,
      despite the fact that doses of the size received by them have been associated
      with more than a doubling in the death rate among the survivors of the Japanese
      atomic bombings.

PMID- 11459731
TI  - Demonstration of correlations between clinical and physical image quality
      measures in chest and lumbar spine screen-film radiography.
AB  - The ability to predict clinical image quality from physical measures is useful
      for optimization in diagnostic radiology. In this work, clinical and physical
      assessments of image quality are compared and correlations between the two are
      derived. Clinical assessment has been made by a group of expert radiologists who
      evaluated fulfillment of the European image criteria for chest and lumbar spine
      radiography using two scoring methods: image criteria score (ICS) and visual
      grading analysis score (VGAS). Physical image quality measures were calculated
      using a Monte Carlo simulation model of the complete imaging system. This model
      includes a voxelized male anatomy and was used to calculate contrast and signal
      to-noise ratio of various important anatomical details and measures of dynamic
      range. Correlations between the physical image quality measures on the one hand
      and the ICS and VGAS on the other were sought. 16 chest and 4 lumbar spine
      imaging system configurations were compared in frontal projection. A
      statistically significant correlation with clinical image quality was found in
      chest posteroanterior radiography for the contrast of blood vessels in the
      retrocardiac area and a measure of useful dynamic range. In lumbar spine
      anteroposterior radiography, a similar significant correlation with clinical
      image quality was found between the contrast and signal-to-noise ratio of the
      trabecular structures in the L1-L5 vertebrae. The significant correlation shows
      that clinical image quality can, at least in some cases, be predicted from
      appropriate measures of physical image quality.

PMID- 11459732
TI  - Radiation carcinogenesis modelling for risk of treatment-related second tumours
      following radiotherapy.
AB  - Radiobiological modelling of the risk of radiation-induced tumours following high
      dose radiation implies a general form for the dose-response relationship.
      Generally, risk will rise with radiation dose at low doses, reach a maximum value
      and then decline with further increase in dose. The magnitude of risk and the
      dose at which this risk is maximum are strongly dependent on the kinetics of
      repopulation by surviving normal and mutant cells and on genetic factors likely
      to differ between tissues and between individuals. The most reliable way to
      reduce the risk of second tumours is to reduce radiation dose further at sites
      where the dose is already low. These sites are usually distant from the primary
      treatment volume. For illustrative purposes, we have compared the predicted
      relative risks of second tumours at "distant sites" for treatment plans giving
      similar dose distributions (dose volume histograms) at the primary site. We
      suggest that dose reduction to distant sites could be of significant benefit in
      reducing the risk of second tumours. Further improvement will require more
      detailed knowledge of the radiation sensitivities and mutagenicities, together
      with the repopulation kinetics of the various cell lineages within the treatment
      volume.

PMID- 11459733
TI  - Performance assessment of the Gulmay D3300 kilovoltage X-ray therapy unit.
AB  - A performance assessment was made of the Gulmay D3300 kilovoltage (combined
      superficial and orthovoltage) X-ray therapy unit. Results are presented for the
      key dosimetric beam parameters required for routine patient treatment. This unit
      is relatively new to the UK market and displayed similar properties to other
      existing equipment. Beam half-value layers were different from comparable
      published data, but were consistent with the actual values of external tube
      filtration employed. The applicator, system interlocks and dose monitor
      performance were satisfactory and the tube leakage was below the UK recommended
      maximum (air kerma rate 300 mGy h(-1) at 5 cm from the tube head). The variation
      of absorbed dose with stand-off distance from the applicator base followed the
      inverse-square law for all tested combinations of beam tube potential (kVp) and
      applicator, and the measured focus-to-surface distances were in acceptable
      agreement with the nominal values. A significant beam profile asymmetry was seen
      for field sizes greater than 10 cm at the upper tube potential (kVp) range
      (maximum ionization quotient 1.08), but this was an inherent property of the X
      ray tube. The difficulties of obtaining percentage depth dose measurements are
      discussed, and it was concluded that the use of published data (appropriately
      verified) was acceptable. The methodology followed could form the basis of an
      acceptance and commissioning protocol. To address the relative lack of agreed
      standards for this type of equipment, performance test tolerances are proposed
      that are recommended for new installations.

PMID- 11459734
TI  - A method of coil localization for breast lesions seen only on MRI.
AB  - Breast lesions may be identified on MRI that are not shown on mammography or
      ultrasound owing to the high sensitivity and relatively poor specificity of
      contrast enhanced MRI. Techniques for diagnostic biopsy of such lesions are not
      widely available. A method is described that uses standard mammographic
      localization methods to place an MR compatible cerebral coil at the site of the
      suspect lesion. Confirmatory MRI can then be obtained before the lesion is
      surgically removed using a mammographic hook wire. This method is described and
      illustrated in detail for one case, and in summary for three further cases, to
      show the potential flexibility of application. The method is commended because it
      is simple and cheap, uses standard breast procedures and can be undertaken
      outside the MRI suite. The procedure will make full use of breast MRI possible to
      those who do not have dedicated localization equipment.

PMID- 11459735
TI  - Reproducibility of quantitative CT perfusion imaging.
AB  - The ability to demonstrate regions of abnormal cerebral blood flow in the setting
      of acute stroke is of diagnostic and prognostic importance. It may also influence
      therapeutic strategies. The advantage of CT perfusion imaging is its ability to
      give quantifiable measurements of cerebral blood flow on any modern CT machine
      without the need to buy specialized equipment. The aim was to assess day-to-day
      variability of values of cerebral blood volume obtained with this technique.
      Seven patients with cerebral gliomas were studied using dynamic CT perfusion
      imaging on two occasions, approximately 24 h apart to reduce variability from
      diurnal variations. Regions of interest were produced in predominately middle
      cerebral artery locations in both hemispheres on the first and second CT
      perfusion studies. Absolute values for cerebral blood flow were produced for
      these regions and were correlated with flows obtained in the same regions of
      interest on the follow-up study. The Pearson correlation coefficient obtained was
      0.884. CT perfusion imaging is easily performed on conventional modern CT
      equipment and demonstrates little variability in measures of absolute cerebral
      blood flow within individuals when studied on two occasions within 24 h.

PMID- 11459736
TI  - Imaging features of pelvic endometriosis.
AB  - Although laparoscopy remains the investigation of choice in the diagnosis of
      endometriosis, imaging does play a significant role in its management. This
      pictorial review concentrates on the techniques used in the imaging of
      endometriosis.

PMID- 11459737
TI  - A right upper zone chest mass in a smoker.

PMID- 11459738
TI  - CT and DSA appearances of ruptured congenital AVM.

PMID- 11459740
TI  - Theoretical and practical implications of dual-task performance in Alzheimer's
      disease.

PMID- 11459741
TI  - Excessive daytime sleepiness: a challenge for the practising neurologist.
AB  - The complaint of excessive daytime sleepiness, commonly encountered in
      neurological practice, may arise from a variety of disorders. The list of
      possibilities spans virtually every major area of medicine, neurology and
      psychiatry. A clear, detailed history is invaluable in negotiating these numerous
      diagnostic considerations; however, the symptom may be expressed in terms that do
      not directly denote somnolence (e.g. 'tiredness' or 'fatigue'). Accurate
      diagnosis is important, not only because of the negative impacts of sleepiness
      and its root causes on health and social function, but because excessive
      sleepiness is generally remediable with appropriate treatment. As our
      understanding of the neurological underpinnings of alertness and sleepiness
      deepens, improved treatment methods are bound to emerge.

PMID- 11459742
TI  - Attentional control in Alzheimer's disease.
AB  - Attentional control of executive function declines during the early stages of
      Alzheimer's disease. Controversy exists as to whether this decline results from a
      single global deficit or whether attentional control can be fractionated, with
      some aspects being more vulnerable than others. We investigated three proposed
      domains of attention, namely (i) focal attention, based on simple and choice
      reaction times; (ii) the capacity to resist distraction in a visual search task;
      and (iii) the capacity to divide attention between two simultaneous tasks. For
      each domain, two levels of difficulty were used to study Alzheimer's disease
      patients, who were compared with elderly and young control subjects. The unitary
      attentional hypothesis predicted that the impacts of level of difficulty, age and
      disease would be qualitatively similar across the three attentional domains. In
      fact we observed different patterns for each domain. We obtained no differential
      impairment for patients in the focal attentional task, whereas patients were
      somewhat more susceptible than control subjects to the similarity of the
      distractor items in visual search. Finally, we observed marked impairment in the
      capacity of Alzheimer's disease patients to combine performance on two
      simultaneous tasks, in contrast to preserved dual-task performance in the normal
      elderly group. These results suggest a need to fractionate executive processes,
      and reinforce earlier evidence for a specific dual-task processing deficit in
      Alzheimer's disease.

PMID- 11459743
TI  - Acute myelopathies: Clinical, laboratory and outcome profiles in 79 cases.
AB  - The main aetiologies of acute myelopathy (AM) are: multiple sclerosis, systemic
      disease (SD), spinal cord infarct (SCI), parainfectious myelopathy (PIM) and
      delayed radiation myelopathy (DRM). Although a large amount of data have been
      published for each individual aetiology, comparison studies are scarce. The aim
      of this study was to assess the various aetiological and outcome profiles of AM.
      We studied 79 cases: 34 (43%) in multiple sclerosis; 13 (16.5%) in SD; 11 (14%)
      in SCI; five (6%) in PIM; and three (4%) in DRM. Myelopathies were of unknown
      origin in 13 (16.5%) patients. We evaluated clinical, spinal cord and brain MRI,
      CSF and evoked potentials data at admission, MRI outcome at 6 months and clinical
      outcome at 12 months. A statistical comparison of clinical, laboratory and
      outcome data was only performed between multiple sclerosis, SD and SCI patients
      due to the small number of cases in the other groups. A motor deficit was more
      frequent in SD and SCI than in multiple sclerosis where initial symptoms were
      predominantly sensory (P < 0.001). Spinal cord MRI showed lateral or posterior
      lesions of less than two vertebral levels in multiple sclerosis, in contrast to
      SD and SCI, where lesions involved more vertebral levels and were centromedullar
      (P < 0.001). Brain MRI was most frequently abnormal in multiple sclerosis (68%),
      but was also abnormal in 31% of SD patients (P < 0.05). Oligoclonal bands in CSF
      were more frequent in multiple sclerosis than in SD (P < 0.001) and were never
      found in SCI. Clinical outcome at 12 months was good in 88% of multiple sclerosis
      cases, and poor or fair in 91% of SCI and 77% of SD. Aetiologies of AM may be
      differentiated on the basis of clinical, spinal cord and brain MRI, CSF and
      outcome data, and allow a probable diagnosis to be made in previously
      undetermined cases. These findings may have therapeutic implications for cases
      with a questionable diagnosis.

PMID- 11459744
TI  - The nature of semantic memory deficits in Alzheimer's disease: new insights from
      hyperpriming effects.
AB  - While semantic memory deficits are a common landmark of Alzheimer's disease, the
      nature of these impairments remains to be clarified. Implicit tasks which assess
      semantic priming effects are often used to understand semantic deficits in
      Alzheimer's disease, but they have led to unclear conclusions because of
      methodological problems such as intervention of attentional mechanisms. To
      explore the effects of semantic priming in Alzheimer's disease and their
      relationship with semantic memory deficits, we used two tasks, one implicit and
      the other explicit. The implicit task was a lexical decision task to assess
      semantic priming, and in which pairs of words had coordinate (tiger-lion) or
      attribute relationships (zebra-stripe). The explicit task was a semantic
      knowledge task composed of namings and questions involving superordinate
      categories and attribute knowledge of concepts. The two tasks systematically
      assessed the integrity of the same concepts. This protocol was given to 53
      Alzheimer's disease patients with mild to moderate dementia and to 20 controls.
      The Alzheimer's disease group as a whole obtained significantly greater priming
      effects (hyperpriming) than controls in the coordinate condition, and equivalent
      priming in the attribute condition. In the coordinate condition, a subgroup of 26
      patients, with attribute knowledge deficits, had larger priming effects than both
      a subgroup without semantic deficits and the control group. These results show
      that in Alzheimer's disease the semantic priming effects vary according to the
      degree of attribute loss, and the presence of hyperpriming would reflect semantic
      memory deficits. This study unravels the fine-grained structure of semantic
      memory disturbances in Alzheimer's disease with mild to moderate dementia,
      affecting initially the attributes of concepts within a hierarchical network in
      which superordinate concepts remain preserved.

PMID- 11459745
TI  - Refractory dyslexia: evidence of multiple task-specific phonological output
      stores.
AB  - We investigated the case of a patient whose reading was characterized by multiple
      phonemic paraphasic errors. An error analysis of a large corpus of reading
      responses (758 words, 86 non-words) highlighted the preponderance of phonological
      errors which did not occur in his naming, repetition or spontaneous speech. His
      comprehension of the written word was relatively preserved, even for words he was
      unable to read aloud. We suggest that his impairment lies at the level of the
      phonological output store. We also demonstrate that his reading performance was
      facilitated by increasing the response-stimulus delay. The strong influence of
      temporal factors is shown to be task-specific. Two main points are drawn from our
      results. First, we argue that our patient can be characterized as having a
      refractory access type of deficit; to our knowledge, no previous case of a
      refractory deficit affecting word reading has been reported. Secondly, the task
      specificity of both the phonological error pattern and the sensitivity to
      temporal factors is difficult to reconcile with the idea of a unitary
      phonological output store. Contrary to orthodox neuropsychological models, we
      propose that there are independent stores specific for reading and spoken output.

PMID- 11459746
TI  - Bacterial peptidoglycan and immune reactivity in the central nervous system in
      multiple sclerosis.
AB  - Multiple sclerosis is believed to result from a CD4+ T-cell response against
      myelin antigens. Peptidoglycan, a major component of the Gram-positive bacterial
      cell wall, is a functional lipopolysaccharide analogue with potent
      proinflammatory properties and is conceivably a mediator of sterile inflammation.
      Here we demonstrate that peptidoglycan is present within antigen-presenting cells
      in the brain of multiple sclerosis patients. These cells have macrophage and
      dendritic cell characteristics, and are immunocompetent as evidenced by co
      expression of inflammatory cytokines and co-stimulatory molecules. In addition,
      intrathecal plasma cells specific for peptidoglycan are present in multiple
      sclerosis brain tissue, and antibodies binding peptidoglycan are present in CSF
      during active disease. Peptidoglycan may thus contribute to T- and B-cell
      activity during brain inflammation without a requirement for local bacterial
      replication.

PMID- 11459747
TI  - Central benzodiazepine receptors in malformations of cortical development: A
      quantitative study.
AB  - We calculated [(11)C]flumazenil volume of distribution ([(11)C]FMZ-V(d)) after
      correction for partial volume effect in 10 patients with malformations of
      cortical development (MCDs) and partial seizures, to quantify the GABA(A)-central
      benzodiazepine receptor complex. Abnormal grey matter and adjacent or overlying
      cortex were outlined individually and added to an individualized anatomical
      template for correction for partial volume effect. Nine of 10 patients showed
      single or multiple increases or decreases in [(11)C]FMZ-V(d) in or around MCDs.
      Two of three patients with band heterotopia showed multiple increases in the
      overlying cortex. In three of four patients with subependymal nodular
      heterotopia, nodules had lower [(11)C]FMZ-V(d) than the overlying cortex, which
      was normal. Decreases in [(11)C]FMZ-V(d) were found in two of three clefts and
      one of six adjacent regions in one schizencephalic patient; another had normal
      [(11)C]FMZ-V(d) in the thickened cortex itself but increases in all adjacent
      regions. Binding was reduced within focal cortical dysplasia but increased in
      adjacent cortex. [(11)C]FMZ-V(d) was normal within one patient's polymicrogyric
      cortex but increased in one of six adjacent volumes of interest. The localization
      of abnormalities correlated with EEG and clinical data in cortical MCDs.
      Flumazenil binding was decreased in some MCDs with increased grey matter volume
      and increased in some adjacent or overlying areas of normal-appearing cortex,
      suggesting functional abnormalities beyond MRI- detectable structural changes.

PMID- 11459748
TI  - Increased intensity perception of aversive taste following right anteromedial
      temporal lobe removal in humans.
AB  - We used a modified version of the Spatial Taste Test to assess taste intensity
      perception in patients with either left or right temporal resection from the
      anteromedial temporal lobe (AMTL), and a group of control subjects. Sweet, sour,
      salty and bitter solutions were applied onto discrete locations of the tongue to
      stimulate either left or right fungiform, or left or right foliate papillae.
      Intensity ratings were assessed with the Labeled Magnitude Scale. Subjects also
      sipped 5 ml of each solution for whole mouth stimulation. Genetically based
      determinants of taste sensitivity were assessed with ratings of 6-n
      propylthiouracil, and covaried from all analyses. As in previous studies,
      analysis of covariance indicated that the subjects in the right temporal group
      rated an aversive bitter taste as more intense than did subjects in the control
      group. In contrast, there were no group differences for sucrose ratings,
      suggesting that the AMTL may be involved preferentially in processing aversive
      compared with hedonic tastes. No group x side, or group x location effects were
      present. These results confirm that removal of the right AMTL in humans results
      in increased taste intensity/aversiveness perception. This finding complements
      existing literature indicating that the AMTL is important for processing aversive
      taste, and suggests that inhibitory mechanisms may play an important role in such
      processing.

PMID- 11459749
TI  - Stereotactic lesional surgery for the treatment of tremor in multiple sclerosis:
      a prospective case-controlled study.
AB  - The effect of stereotactic lesional surgery for the treatment of tremor in
      multiple sclerosis was examined in a prospective case-controlled study. Surgery
      was not undertaken in 33 patients (72% of 46 cases referred for stereotactic
      surgery), two of whom died within 4 months of referral. Twenty-four multiple
      sclerosis patients were included in the study; 13 underwent surgery and were
      matched against 11 controls on the basis of age, sex, expanded disability system
      scores (EDSS) and disease duration. Assessments were carried out at
      baseline/preoperatively, and then 3 and 12 months later; these included
      accelerometric and clinical ratings of tremor, spirography, handwriting, a finger
      tapping test, nine-hole peg test, tremor-related disability, general neurological
      examination, Barthel Activities of Daily Living (ADL) Index of general
      disability, EDSS, a 0-4 ataxia scale, Mini-Mental State (MMS) examination, speech
      and swallowing assessments and grip strength. Postoperative MRI scans
      demonstrated that tremor could be attenuated by lesions centred on the thalamus
      in seven cases, on the zona incerta in five cases and in the subthalamic nucleus
      in one case. Two patients developed hemiparesis and in two cases epilepsy
      recurred. Two surgical patients and one control patient died between the 3 and 6
      months assessments. Both groups had a significant deterioration in EDSS but not
      Barthel ADL Index scores at 1 year, but the difference between the groups was not
      significant. Similarly, no differences between the groups' rates of deterioration
      of speech or swallowing or MMS were found. Significant improvements in
      contralateral upper limb postural (P2) and kinetic tremors, spiral scores and
      head tremor were detected at 3 and 12 months after surgery (but not handwriting
      or nine-hole peg test performance). Tremor-related disability and finger-tapping
      speed were also significantly better 12 months after surgery, the latter having
      significantly worsened for the control group. A 3 Hz 'filter' for postural (P2)
      upper limb tremor was detected by accelerometry/spectral analysis above which
      tremor was always abolished and at or below which some residual tremor invariably
      remained. Criteria for selecting multiple sclerosis patients for this form of
      surgery are discussed.

PMID- 11459750
TI  - Effect of bilateral subthalamic nucleus stimulation on gait in Parkinson's
      disease.
AB  - The fundamental disturbance of the parkinsonian gait is the reduction in walking
      velocity. This is mainly due to reduction in stride length, while cadence
      (steps/min) is slightly enhanced. Treatment with L-dopa increases stride length
      while cadence is unchanged. Chronic stimulation of the thalamus has no effect on
      Parkinsonian gait. The efficacy of electrical stimulation of the subthalamic
      nucleus (STN) on gait in advanced Parkinson's disease has been clearly
      demonstrated clinically. The aim of the present study was to quantify the changes
      in gait measures induced by STN stimulation and L-dopa and to assess possible
      differential or additive effects. Eight Parkinson's disease patients (mean +/- SD
      age 48.1 +/- 7.3 years) with chronic bilateral STN stimulation (mean duration of
      disease 13.3 +/- 2.4 years, mean stimulation time 15.4 +/- 10.6 months) and 12
      age-matched controls were investigated. Subjects walked on a special treadmill
      with a closed-loop ultrasound control system that used the subject's position to
      adjust treadmill speed continuously for the actual walking velocity. In an
      appropriate crossover design, spatiotemporal gait measures and leg joint angle
      movements were assessed for at least 120 stride cycles in four treatment
      conditions: with and without stimulation and with and without a suprathreshold
      dose of L-dopa. With STN stimulation, there were increases of almost threefold in
      mean walking velocity (from 0.35 to 0.96 m/s) and stride length (from 0.34 to
      0.99 m). Cadence remained constant. The range of motion of the major leg joints
      also increased. L-Dopa alone had a slightly weaker effect, with an increase in
      walking velocity to 0.94 m/s and in stride length to 0.92 m at a similar cadence.
      These increased values were in the range of those for healthy age-matched
      subjects performing the same task. The combination of both treatments further
      increased the mean walking velocity to 1.19 m/s and stride length to 1.20 m at an
      unchanged cadence. However, not all patients receiving STN stimulation improved
      further when they also received L-dopa. These results demonstrate that chronic
      bilateral STN stimulation, like treatment with L-dopa, improves walking velocity
      by increasing stride length without changing cadence. STN stimulation almost
      exclusively affects mechanisms involved in the control of spatial gait measures
      rather than rhythmicity. The gait measures obtained with STN stimulation alone
      are in the range of control subjects.

PMID- 11459751
TI  - Networks mediating the clinical effects of pallidal brain stimulation for
      Parkinson's disease: a PET study of resting-state glucose metabolism.
AB  - Employing [(18)F]fluorodeoxyglucose (FDG) and PET, we have found previously that
      stereotaxic ablation of the internal globus pallidus (GPi) for Parkinson's
      disease causes resting metabolic changes in brain regions remote from the lesion
      site. In this study we determined whether similar metabolic changes occur in
      Parkinson's disease patients treated with deep brain stimulation (DBS) of the
      GPi. We studied seven Parkinson's disease patients with FDG-PET to measure
      resting regional cerebral glucose utilization on and off GPi stimulation. We used
      statistical parametric mapping to identify significant changes in regional brain
      metabolism that occurred with this intervention. We also quantified stimulation
      related changes in the expression of a specific abnormal Parkinson's disease
      related pattern of metabolic covariation (PDRP) that had been identified in
      earlier FDG-PET studies. Metabolic changes with DBS were correlated with clinical
      improvement as measured by changes in Unified Parkinson's Disease Rating Scale
      (UPDRS) motor ratings off medication. GPi DBS improved UPDRS motor ratings (36%,
      P < 0.001) and significantly increased regional glucose metabolism in the
      premotor cortex ipsilateral to stimulation and in the cerebellum bilaterally. GPi
      DBS also resulted in a significant (P < 0.01) decline in PDRP activity
      ipsilateral to stimulation, which correlated significantly with clinical
      improvement in UPDRS motor ratings (P < 0.03). Clinical improvement with GPi DBS
      is associated with reduced expression of an abnormal Parkinson's disease-related
      metabolic network involving elements of the cortico-striato-pallido
      thalamocortical and the cerebello-cortical motor loops.

PMID- 11459752
TI  - Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome.
AB  - This study utilized MRI data to describe neuroanatomical morphology in children
      and adolescents with fragile X syndrome, the most common inherited cause of
      developmental disability. The syndrome provides a model for understanding how
      specific genetic factors can influence both neuroanatomy and cognitive capacity.
      Thirty-seven children and adolescents with fragile X syndrome received an MRI
      scan and cognitive testing. Scanning procedures and analytical strategies were
      identical to those reported in an earlier study of 85 typically developing
      children, permitting a comparison with a previously published template of normal
      brain development. Regression analyses indicated that there was a normative age
      related decrease in grey matter and an increase in white matter. However, caudate
      and ventricular CSF volumes were significantly enlarged, and caudate volumes
      decreased with age. Rates of reduction of cortical grey matter were different for
      males and females. IQ scores were not significantly correlated with volumes of
      cortical and subcortical grey matter, and these relationships were statistically
      different from the correlational patterns observed in typically developing
      children. Children with fragile X syndrome exhibited several typical
      neurodevelopmental patterns. Aberrations in volumes of subcortical nuclei, gender
      differences in rates of cortical grey matter reduction and an absence of
      correlation between grey matter and cognitive performance provided indices of the
      deleterious effects of the fragile X mutation on the brain's structural
      organization.

PMID- 11459753
TI  - The neural representation of nouns and verbs: PET studies.
AB  - Neuropsychological studies of patients with selective deficits for nouns or verbs
      have been taken as evidence for the neural specialization of different word
      classes. Noun deficits are associated with lesions in anterior temporal regions
      while verb deficits arise from left inferior frontal lesions. However,
      neuroimaging studies do not unequivocally support this account, with only some
      studies supporting claims for regional specialization. We carried out two PET
      studies to determine whether there is any regional specialization for the
      processing of nouns and verbs. One study used the lexical decision task and the
      other used a more semantically demanding task, i.e. semantic categorization. We
      found robust activation of a semantic network extending from left inferior
      frontal cortex into the inferior temporal lobe, but no differences as a function
      of word class. We interpret these data within the framework of cognitive accounts
      in which conceptual knowledge is represented within a non-differentiated
      distributed system.

PMID- 11459754
TI  - Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased
      yield of active demyelinating and (p)reactive lesions.
AB  - Macroscopic sampling of multiple sclerosis lesions in the brain tends to find
      chronic lesions. For a better understanding of the dynamics of the multiple
      sclerosis disease process, research into new and developing lesions is of great
      interest. As MRI in vivo effectively demonstrates lesions in multiple sclerosis
      patients, we have applied it to unfixed post-mortem brain slices to identify
      abnormalities, in order to obtain a higher yield of active lesions. The
      Netherlands Brain Bank organized the rapid autopsy of 29 multiple sclerosis
      patients. The brain was cut in 1 cm coronal slices. One or two slices were
      subjected to T(1)- and T(2)-weighted MRI, and then cut at the plane of the MRI
      scan into 5 mm thick opposing sections. Areas of interest were identified based
      on the MRI findings and excised. One half was fixed in 10% formalin and paraffin
      embedded, and the corresponding area in the adjacent half was snap-frozen in
      liquid nitrogen. In total, 136 out of 174 brain tissue samples could be matched
      with the abnormalities seen on T(2)-weighted MRIs. The stage of lesional
      development was determined (immuno) histochemically. For 54 MRI-detectable
      samples, it was recorded whether they were macroscopically detectable, i.e.
      visible and/or palpable. Histopathological analysis revealed that 48% of the
      hyperintense areas seen on T(2)-weighted images represented active lesions,
      including lesions localized in the normal appearing white matter, without
      apparent loss of myelin but nevertheless showing a variable degree of oedema,
      small clusters of microglial cells with enhanced major histocompatibility complex
      class II antigen, CD45 and CD68 antigen expression and a variable number of
      perivascular lymphocytes around small blood vessels [designated as (p)reactive
      lesions]. From the macroscopically not-visible/not-palpable MRI-detected
      abnormalities, 58% were (p)reactive lesions and 21% contained active
      demyelinating lesions. In contrast, visible and/or palpable brain tissue samples
      mainly contained chronic inactive lesions. We conclude that MRI-guided sampling
      of brain tissue increases the yield of active multiple sclerosis lesions,
      including active demyelinating and (p)reactive lesions.

PMID- 11459755
TI  - Visual vertigo: symptom assessment, spatial orientation and postural control.
AB  - Certain patients with balance disorders report a 'visual vertigo' in which their
      symptoms are provoked or aggravated by specific visual contexts (e.g.
      supermarkets, driving or movement of objects). In order to determine the causes
      of visual vertigo (VV), we assessed symptoms, anxiety and the influence of
      disorienting visual stimuli in 21 such patients. In 17 out of 21 patients, a
      peripheral vestibular disorder was diagnosed. Sixteen bilateral labyrinthine
      defective subjects (LDS) and 25 normal subjects served as controls. Questionnaire
      assessment showed that the levels of trait anxiety and childhood motion sickness
      in the three subject groups were not significantly different. Reporting of
      autonomic symptoms and somatic anxiety was higher than normal in both patient
      groups but not significantly different between LDS and VV patients. Handicap
      levels were not different in the two patient groups, but the reporting of
      vestibular symptoms was higher in the VV than in the LDS group. The experimental
      stimuli required subjects to set the subjective visual vertical in three visual
      conditions: total darkness, in front of a tilted luminous frame (rod and frame
      test) and in front of a large disc rotating in the frontal plane (rod and disc
      test). Body sway was also measured in four visual conditions: eyes closed, eyes
      open, facing the tilted frame and during disc rotation. In psychophysical and
      postural tests, both LDS and VV patients showed: (i) a significant increase in
      the tilt of the visual vertical both with the static tilted frame and with the
      rotating disc; and (ii) an increased postural deviation whilst facing the tilted
      frame and the rotating disc. The ratio between sway path with eyes closed and
      eyes open (i.e. the stabilizing effect of vision) was increased in the LDS, but
      not in VV patients, compared with normal subjects. In contrast, the ratio between
      sway path during disc rotation and sway path during eyes open (i.e. the
      destabilizing effect of a moving visual stimulus) was increased in the VV
      patients but not in LDS. Taken together, these data show that VV patients have
      abnormally large perceptual and postural responses to disorienting visual
      environments. VV is not related to trait anxiety or a past history of motion
      sickness. The results indicate that VV emerges in vestibular patients if they
      have increased visual dependence and difficulty in resolving conflict between
      visual and vestibulo-proprioceptive inputs. It is argued that treating these
      patients with visual motion desensitization, e.g. repeated optokinetic
      stimulation, should be beneficial.

PMID- 11459756
TI  - Behavioural relevance of atypical language lateralization in healthy subjects.
AB  - In most humans, language is lateralized to the left side of the brain. It has
      been speculated that this hemispheric specialization is a prerequisite for the
      full realization of linguistic potential. Using standardized questionnaires and
      performance measures, we attempted to determine if there are behavioural
      correlates of atypical, i.e. right-hemispheric and bilateral, language
      lateralization. The side and degree of language lateralization were determined by
      measuring the hemispheric perfusion differences by functional transcranial
      Doppler ultrasonography during a word generation task in healthy volunteers.
      Subjects with left (n = 264), bilateral (n = 31) or right (n = 31) hemisphere
      language representation did not differ significantly with respect to mastery of
      foreign languages, academic achievement, artistic talents, verbal fluency or (as
      assessed in a representative subgroup) in intelligence or speed of linguistic
      processing. These findings suggest that atypical hemispheric specialization for
      language, i.e. right-hemisphere or bilateral specialization, is not associated
      with major impairments of linguistic faculties in otherwise healthy subjects.

PMID- 11459757
TI  - Progressive supranuclear palsy as a disease phenotype caused by the S305S tau
      gene mutation.

PMID- 11459758
TI  - Cellular diversity in mouse neocortex revealed by multispectral analysis of amino
      acid immunoreactivity.
AB  - Cortical cells were classified using an unsupervised cluster analysis based upon
      their quantitative and combinatorial immunoreactivity for glutamate, gamma
      aminobutyric acid (GABA), aspartate, glutamine and taurine. Overall, cell class
      specific amino acid signatures were found for 12 cellular types; seven GABA
      immunoreactive (GABA-IR) populations (GABA1--7), three classes containing high
      glutamate levels (GLUT1--3) and two putative glial (GLIA1, 2) cell types. From
      their large somata, associated vertical processes and high glutamate content, the
      GLUT classes most probably correspond to pyramidal neurons. Two of the GLUT
      classes demonstrated complementary distributions in different cortical layers,
      suggesting spatial separation of cells differing in amino acid immunoreactivity.
      Of the seven GABA classes, two comprised cells with large somata and displayed
      medium to low glutamate levels. On the basis of size, these two populations may
      correspond to large basket cell interneurons. Glial populations could be divided
      into two classes: GLIA1 cells were more frequently associated with blood vessels
      and GLIA2 cells were more commonly seen in the lower cortical layers. This work
      demonstrates that signature recognition based upon amino acid content can be used
      to separate cortical cells into different categories and reveal further
      subclasses within these categories. This approach is complementary to other
      methods using physiological and molecular tools and ultimately will enhance our
      understanding of neuronal heterogeneity.

PMID- 11459759
TI  - Thalamo-cortical afferents control transient expression of the dopamine D(3)
      receptor in the rat somatosensory cortex.
AB  - The D(3) dopamine receptor (D(3)R) is selectively and transiently expressed in
      the barrel neurons of the somatosensory cortex (SI) between the first and second
      postnatal weeks. The D(3)R expression starts after the initial ingrowth of
      thalamocortical afferents (TCAs) into the barrel cortex and could be induced or
      controlled by them. We show that unilateral electrolytic lesion of the thalamic
      ventrobasal complex immediately after birth leads to a decrease in the D(3)R mRNA
      concentration in the lesioned SI 7 days after the lesion, whereas the D(3)R
      binding is little affected. Fourteen days after the neonatal thalamic lesion, the
      D(3)R binding and mRNA are drastically reduced and the barrel-like pattern of the
      D(3)R is absent. Elevation of the D(3) binding normally seen between the first
      and second postnatal weeks does not occur. Thalamic lesion on P6 differentially
      affects the D(3)R expression. One day after the lesion, the D(3) binding and mRNA
      are down-regulated, but the effect is transient. Five days after the lesion the
      concentration of D(3) mRNA in the lesioned hemisphere returns to the control
      level. The typical barrel-like pattern of D(3)R expression is evident in the
      lesioned SI, although TCAs are completely absent. Quantitative analysis
      demonstrated elevated cellular levels of the D(3) mRNA in barrel neurons 5 days
      after the lesion. These higher levels are needed, perhaps, to support the
      increased production of the D(3)R protein appropriate for this age. Age-related
      dynamics of the D(3)R binding is retained in the lesioned SI, although the
      concentration of D(3)R sites remains reduced. These data demonstrate that intact
      thalamic input is essential for the formation of mechanisms responsible for
      developmental regulation of the D(3)R expression in the SI.

PMID- 11459760
TI  - Structure--function spatial covariance in the human visual cortex.
AB  - The value of sulcal landmarks for predicting functional areas was quantitatively
      examined. Medial occipital sulci were identified using anatomical magnetic
      resonance images to create individual cortical-surface models. Functional visual
      areas were identified using retinotopically organized visual stimuli, and
      positron emission tomography subtraction imaging with intra-subject averaging.
      Functional areas were assigned labels by placement along the cortical surface
      from V1. Structure-function spatial covariances between sulci and functional
      areas, and spatial covariances among functional areas, were determined by
      projecting sulcal landmarks and functional areas into a standardized stereotaxic
      space and computing the 'r' statistics. A functional area was considered to
      spatially covary with a sulcus or another functional area if their geometric
      centers correlated significantly (P < 0.05) in two or more axes. Statistically
      significant spatial covariances were found for some, but not all comparisons. The
      finding of significant spatial covariances within a standardized stereotaxic
      space indicates that nine-parameter spatial normalization does not account for
      all the predictive value of structural or functional locations, and may be
      improved upon by using selected sulcal and functional landmarks. The present
      findings quantify for the first time the strength of structure--function spatial
      covariance and comment directly on developmental theories addressing the etiology
      of structure--function correspondence.

PMID- 11459761
TI  - Juvenile emotional experience alters synaptic inputs on pyramidal neurons in the
      anterior cingulate cortex.
AB  - Analogous to the experience-driven development of sensory systems, the functional
      maturation of limbic circuits is significantly influenced by early socio
      emotional experience. In a combined light and electron microscopic study in the
      anterior cingulate cortex of Octodon degus, the densities of spine and shaft
      synapses on apical dendrites of layer III pyramidal neurons were compared in 45
      day old (1) undisturbed control animals; (2) handled animals; (3) animals which
      were repeatedly maternally deprived during the first three postnatal weeks; (4)
      animals which were treated similarly to group 3 and thereafter kept in chronic
      social isolation. Animals in groups 2-4 showed significantly higher spine
      densities (up to 121%, 142% and 151% respectively) compared to control group 1.
      Group 3 displayed significantly longer apical dendrites compared to control group
      1. The electron microscopic analysis in cortical layer II revealed significantly
      higher spine synapses in group 4 (up to 166%) and fewer shaft synapses in groups
      3 and 4 (down to 53% and 65% respectively) compared to group 1. These results
      demonstrate that early traumatic emotional experience alters synaptic input of
      pyramidal neurons. Such experience-induced modulation of limbic cortex
      development may determine psychosocial and cognitive capacities during later
      life.

PMID- 11459762
TI  - The cannabinoid receptor agonist WIN 55,212-2 regulates glutamate transmission in
      rat cerebral cortex: an in vivo and in vitro study.
AB  - The effects of the cannabinoid receptor agonist WIN 55,212-2 on endogenous
      extracellular glutamate levels in the prefrontal cortex of the awake rat and in
      primary cultures of rat cerebral cortex neurons were investigated. In the
      prefrontal cortex WIN 55,212-2 (0.1 and 1 mg/kg i.p.) increased dialysate
      glutamate levels from of the awake rat, while the lower (0.01 mg/kg) and the
      higher (2 mg/kg) doses were ineffective. Furthermore, the WIN 55,212-2 (0.1
      mg/kg)- induced increase of dialysate glutamate levels was counteracted by
      pretreatment with the selective CB(1) receptor antagonist SR141716A (0.1 mg/kg
      i.p.) and by the local perfusion with a low-calcium Ringer solution (Ca(2+) 0.2
      mM). In primary cultures of rat cerebral cortex neurons, WIN 55,212-2 (0.01--100
      nM) increased extracellular glutamate levels, displaying a bell-shaped
      concentration-response curve. The facilitatory effect of WIN 55,212-2 (1 nM) was
      fully counteracted by SR141716A (10 nM), by the replacement of the normal Krebs
      Ringer-bicarbonate buffer with a low Ca(2+) medium (0.2 mM) and by the IP(3)
      receptor antagonist xestospongin C (1 microM). These in vivo and in vitro
      findings suggest an increase in cortical glutamatergic transmission by CB(1)
      receptors, an effect that may underlie some of the psychoactive and behavioural
      actions of acute exposure to marijuana.

PMID- 11459763
TI  - Altered interneuron development in the cerebral cortex of the flathead mutant.
AB  - One approach to defining mechanisms essential to neocortical development is to
      analyze the phenotype of novel spontaneous mutations that dramatically affect the
      generation and differentiation of different neocortical neurons. Previously we
      have shown that there is a large decrease in the total number of cortical neurons
      in the flathead mutant rat, and in this paper we show that the flathead (fh/fh)
      mutation causes an even larger decrease in the number of interneurons. The
      decrease in relative interneuron number is different in different cortical lamina
      and for different interneuron subtypes. Specifically, the percentage of GABA and
      calretinin- positive cells in upper layers of somatosensory cortex is not
      appreciably decreased in homozygous mutants, while other interneuron subtypes in
      somatosensory cortex and all GABA-positive interneuron types in entorhinal cortex
      are decreased. In addition, the soma and dendritic arbors of interneurons in
      flathead are greatly hypertrophied, while those of pyramidal neurons are not.
      Furthermore, we found that at embryonic day 14, flathead mutants display high
      levels of cell death throughout both the neocortical and ganglionic eminence (GE)
      proliferative zones with a larger increase in cell death in the GE than in the
      neocortical VZ. In addition, we provide evidence that there is widespread
      cytokinesis failure resulting in binucleate pyramidal cells and interneurons, and
      the number of binucleate interneurons is greater than the number of binucleate
      pyramidal neurons. Together, these results demonstrate that the fh mutation
      causes dramatic alterations in interneuron development, and suggest that the
      flathead mutation causes differential cytokinesis failure and cell death in
      different types of neocortical progenitors.

PMID- 11459764
TI  - GABA(B) receptors mediate motility signals for migrating embryonic cortical
      cells.
AB  - During development, postmitotic neurons migrate from germinal regions into the
      cortical plate (cp), where lamination occurs. In rats, GABA is transiently
      expressed in the cp, near target destinations for migrating neurons. In vitro
      GABA stimulates neuronal motility, suggesting cp cells release GABA, which acts
      as a chemoattractant during corticogenesis. Pharmacological studies indicate GABA
      stimulates migration via GABA(B)-receptor (GABA(B)-R) activation. Using
      immunohistochemistry, RT-PCR and Western blotting, we examined embryonic cortical
      cell expression of GABA(B)-Rs in vivo. At E17, GABA(B)-R1(+) cells were
      identified in the ventricular zone (vz) and cp. RT-PCR and Western blotting
      demonstrated the presence of GABA(B)-R1a and GABA(B)-R1b mRNA and proteins. Using
      immuno- cytochemistry, GABA(B)-R expression was examined in vz and cp cell
      dissociates before and after migration to GABA in an in vitro chemotaxis assay.
      GABA-induced migration resulted in an increase of GABA(B)-R(+) cells in the
      migrated population. While <20% of each starting dissociate was GABA(B)-R(+),
      >70% of migrated cells were immunopositive. We used a microchemotaxis assay to
      analyze cp cell release of diffusible chemotropic factor(s). In vitro, cp
      dissociates induced vz cell migration in a cell density-dependent manner that was
      blocked by micromolar saclofen (a GABA(B)-R antagonist). HPLC demonstrated cp
      cells release micromolar levels of GABA and taurine in several hours. Micromolar
      levels of both molecules stimulated cell migration that was blocked by micromolar
      saclofen. Thus, migratory cortical cells express GABA(B)-Rs, cp cells release
      GABA and taurine, and both molecules stimulate cortical cell movement. Together
      these findings suggest GABA and/or taurine act as chemoattractants for neurons
      during rat cortical histogenesis via mechanisms involving GABA(B)-Rs.

PMID- 11459765
TI  - Functional anatomy of musical perception in musicians.
AB  - The present study used functional magnetic resonance to examine the cerebral
      activity pattern associated with musical perception in musicians and non
      musicians. Musicians showed left dominant secondary auditory areas in the
      temporal cortex and the left posterior dorsolateral prefrontal cortex during a
      passive music listening task, whereas non-musicians demonstrated right dominant
      secondary auditory areas during the same task. A significant difference in the
      degree of activation between musicians and non-musicians was noted in the
      bilateral planum temporale and the left posterior dorsolateral prefrontal cortex.
      The degree of activation of the left planum temporale correlated well with the
      age at which the person had begun musical training. Furthermore, the degree of
      activation in the left posterior dorsolateral prefrontal cortex and the left
      planum temporale correlated significantly with absolute pitch ability. The
      results indicated distinct neural activity in the auditory association areas and
      the prefrontal cortex of trained musicians. We suggest that such activity is
      associated with absolute pitch ability and the use-dependent functional
      reorganization produced by the early commencement of long-term training.

PMID- 11459766
TI  - Responses of neurons in macaque area V4 during memory-guided visual search.
AB  - In a typical scene with many different objects, attentional mechanisms are needed
      to select relevant objects for visual processing and control over behavior. To
      test the role of area V4 in the selection of objects based on non-spatial
      features, we recorded from V4 neurons in the monkey, using a visual search
      paradigm. A cue stimulus was presented at the center of gaze, followed by a blank
      delay period. After the delay, a two-stimulus array was presented extrafoveally,
      and the monkey was rewarded for detecting the target stimulus matching the cue.
      The array was composed of one 'good' stimulus (effective in driving the cell when
      presented alone) and one 'poor' stimulus (ineffective in driving the cell when
      presented alone). When the choice array was presented in the receptive field (RF)
      of the neuron, many cells showed suppressive interactions between the stimuli as
      well as strong attention effects. Within 150--200 ms of array onset, responses to
      the array were determined by the target stimulus. If the target was the good
      stimulus, the response to the array became equal to the response to the good
      stimulus presented alone. If the target was the poor stimulus, the response
      approached the response to that stimulus presented alone. Thus the influence of
      the nontarget stimulus was filtered out. These effects were reduced or eliminated
      when the poor stimulus was located outside the RF and, therefore, no longer
      competing for the cell's response. Overall, the results support a 'biased
      competition' model of attention, according to which objects in the visual field
      compete for representation in the cortex, and this competition is biased in favor
      of the behaviorally relevant object.

PMID- 11459767
TI  - Temporal spatial differences observed by functional MRI and human intraoperative
      optical imaging.
AB  - Pre-operative functional magnetic resonance imaging (fMRI), cortical evoked
      potentials (EPs) and intraoperative optical imaging of intrinsic signals (iOIS)
      were employed to relate the temporal-spatial characteristics of sensorimotor
      responses in human brain. Peripheral somasthetic stimulation (2 s) was provided
      either by a 110 Hz finger vibrator or transcutaneous median nerve stimulation in
      eight patients undergoing neurosurgical procedures. Each technique provided
      unique spatial patterns and temporal response profiles. EPs and iOIS activities
      were observed over the surface of pre- and post-central gyri (at the level of the
      superior genu) with very similar spatial distributions. In contrast, fMRI spatial
      distributions depended upon the model used for statistical correlation analysis.
      Using a monophasic response model, fMRI primarily localized within the central
      sulcus and did not demonstrate large signal changes over the pre- and post
      central gyri (areas with iOIS/EP activity). However, as initial negative
      responses were incorporated into the response model, fMRI progressively localized
      closer to the iOIS and somatosensory EP maps. Temporally, responses to single
      stimuli differed between the fMRI and iOIS techniques. Using a monophasic model
      for fMRI analysis, the total fMRI response was delayed by 2--3 s relative to
      iOIS. As initial negative responses were incorporated in the analysis, the fMRI
      time course developed temporal characteristics similar to iOIS. Ultimately, when
      fMRI time courses were examined over pixels co-localizing with iOIS activation
      (without using statistical correlation analysis), the fMRI temporal profile
      included an initial decrease in signal (an initial dip) that closely resembled
      the time course of iOIS response. This is the first study to experimentally co
      localize (temporally and spatially) iOIS and fMRI signals in human subjects. The
      spatial/temporal differences in this study likely reflect the capillary versus
      venous contributions of iOIS and fMRI, respectively. The temporal/spatial co
      localization of the iOIS signal and the fMRI initial dip suggests the initial
      fMRI dip and the iOIS signal may result from similar physiologic events.

PMID- 11459768
TI  - Minireview: sex differentiation.
AB  - Mammalian sex differentiation is a hormone-dependent process in the male
      following the determination of a testis from the indifferent gonad through a
      cascade of genetic events. Female sex differentiation is not dependent on ovarian
      hormones, yet there is evidence that members of the Wnt family of developmental
      signaling molecules play a role in Mullerian duct development and in suppressing
      Leydig cell differentiation in the ovary. The testis induces male sex
      differentiation (including testis descent) through a time-dependent production of
      optimal concentrations of anti-Mullerian hormone, insulin-like factor(s) and
      androgens. Observations in several human syndromes of disordered fetal sex
      development corroborate findings in murine embryo studies, although there are
      exceptions in some gene knockout models. The ubiquitously expressed AR interacts
      in a ligand-dependent manner with coregulators to control the expression of
      androgen-responsive genes. Preliminary studies suggest the possibility of hormone
      resistance syndromes associated with coregulator dysfunction. Polymorphic
      variants in genes controlling androgen synthesis and action may modulate
      androgenic effects on sex differentiation.

PMID- 11459769
TI  - Hypothalamic melanocortin signaling in cachexia.

PMID- 11459770
TI  - Reversal of cancer anorexia by blockade of central melanocortin receptors in
      rats.
AB  - Anorexia is a debilitating manifestation of many malignancies. The etiology of
      cancer anorexia is poorly understood, and effective treatment options are
      limited. To investigate the role of central melanocortin receptor signaling in
      the pathogenesis of cancer anorexia, we assessed the effects on food intake of
      the melanocortin receptor antagonist SHU9119 administered into the third cerebral
      ventricle of Lobund-Wistar rats that were anorexic from prostate cancer. In
      anorexic tumor-bearing rats, daily treatment with SHU9119 (0.35 nmol,
      intracerebroventricularly) increased food intake from 71 +/- 3% to 110 +/- 6% of
      preanorectic baseline and caused significant weight gain (13 +/- 5 vs. 5 +/- 1
      g/3 d, SHU9119 vs. baseline in tumor-bearing rats). In control rats pair-fed to
      the intake of tumor-bearing animals, SHU9119 was ineffective at increasing food
      intake. The specificity of the SHU9119 feeding response was assessed using two
      other orexigenic peptides, NPY and the novel hormone ghrelin. Treatment of tumor
      bearing rats with intracerebroventricular ghrelin (10 microg) increased food
      intake, but the effect was blunted relative to that in controls.
      Intracerebroventricular injections of NPY (1 microg) also failed to reverse
      anorexia in tumor-bearing rats. Because SHU9119 completely reverses cancer
      anorexia in this model, whereas ghrelin and NPY do not, increased central nervous
      system melanocortin signaling is implicated in the pathogenesis of this disorder.
      This suggests that new targets for the treatment of cancer anorexia may be found
      in the melanocortin pathways.

PMID- 11459771
TI  - Decreased expression of steroidogenic acute regulatory protein: a novel mechanism
      participating in the leptin-induced inhibition of glucocorticoid biosynthesis.
AB  - The adipocyte-derived hormone leptin is a central modulator of food intake,
      metabolism and neuroendocrine functions. It is also involved in a physiological
      loop linking the activity of the hypothalamo-pituitary-adrenal axis and adipose
      tissue. At the adrenal level, leptin has been shown to antagonize the effects of
      ACTH on glucocorticoid biosynthesis by decreasing the expression of various
      enzymes of the steroid biosynthetic pathway. The steroidogenic acute regulatory
      protein regulates cholesterol delivery to the P450(scc) enzyme, a process that is
      rate limiting in steroid hormone biosynthesis. We have demonstrated here that
      leptin significantly inhibits the expression of steroidogenic acute regulatory
      protein in primary cultures of rat adrenocortical cells. This inhibition was
      observed at both the protein and mRNA levels. In contrast, leptin was not found
      to interfere with the expression of the cytosolic enzyme cholesterol ester
      hydrolase or with that of the mitochondrial enzyme P450(scc). In addition, we
      observed the anticipated stimulation of cAMP production by ACTH in the presence
      of leptin, suggesting that it does not interfere with intracellular ACTH
      signaling. In summary, our data provide evidence that the interplay existing
      between leptin and ACTH in vivo is mediated at least partially via a direct and
      opposite modulation of steroidogenic acute regulatory protein, a key factor in
      the adrenal steroid biosynthetic pathway. This effect of leptin could also be
      relevant to other steroidogenic tissues.

PMID- 11459772
TI  - Testosterone and estrogen act via different pathways to inhibit puberty in the
      male Siberian hamster (Phodopus sungorus).
AB  - The peripubertal transition in male mammals is accompanied by a gradual decrease
      in sensitivity to the inhibitory effects exerted by gonadal hormones, such as T
      and E2. Here, we investigated the effects of chronic T and its metabolites,
      5alpha-dihydrotestosterone and E2 on the hypothalamo-pituitary-gonadal axis at
      puberty. We also examined if T effects are distinct or mediated through its
      conversion to 5alpha-dihydrotestosterone or E2. Twenty-day-old male Siberian
      hamsters were sc implanted with a SILASTIC brand capsule containing varying doses
      of T, 5alpha-dihydrotestosterone, or E2. Several functional parameters of the
      hypothalamo-pituitary-gonadal axis were evaluated including hypothalamic GnRH
      concentration, pituitary and plasma FSH levels, pituitary FSH and LH mRNA, and
      testicular status. Our results showed that gonadal steroids inhibited puberty in
      a dose-dependent manner as evaluated by testes mass (undiluted steroid: T, 27 +/-
      3 mg; 5alpha-dihydrotestosterone, 18 +/- 1 mg; and E2, 62 +/- 4 mg relative to
      cholesterol-implanted controls, 510 +/- 42 mg). Also, T decreased plasma FSH
      below detectable levels, but pituitary FSH concentration was unaffected (1.37 +/-
      0.16 ng/microg protein) while E2-treated hamsters had normal plasma FSH levels
      (3.5 +/- 0.98 ng/ml) yet significantly lower pituitary FSH concentration (0.09 +/
      0.04 ng/microg protein). These results showed that the pathways of T and E2
      action on the hypothalamo-pituitary-gonadal axis are distinct.

PMID- 11459773
TI  - Vascular function and blood pressure in GH transgenic mice.
AB  - Acromegaly is associated with cardiovascular disease. We studied vascular
      function and mean arterial blood pressure in transgenic mice overexpressing
      bovine GH. Mean arterial blood pressure was measured in conscious, unrestrained
      male and female bovine GH and littermate control mice during normal as well as
      high salt intake using telemetric devices. Structure in artificially perfused
      maximally dilated hindquarter vascular beds and vascular reactivity and
      endothelial function in small mesenteric vessels were studied in female bovine GH
      and control mice. Mean arterial blood pressure was increased in female bovine GH
      transgenic (126 +/- 3 mm Hg) and male bovine GH transgenic (129 +/- 4 mm Hg)
      compared with female (109 +/- 3 mm Hg, P < 0.05) and male (111 +/- 3 mm Hg, P <
      0.05) controls respectively. Increased salt intake had no effect on mean arterial
      blood pressure. Perfusion studies showed a significant decrease in the average
      diameter of the female bovine GH transgenic hindquarter vascular bed (P < 0.05).
      The responses of isolated resistance arteries to nor-epinephrine, potassium
      induced depolarization, acetylcholine, or sodium-nitroprusside did not
      significantly differ between bovine GH transgenic and control mice. We conclude
      that the phenotype of the bovine GH transgenic mice includes a salt-resistant
      form of hypertension. Furthermore, the increase in mean arterial blood pressure
      is accompanied by a significant structural narrowing of the resistance
      vasculature without changes in vascular reactivity or endothelial function. The
      results imply that hypertension in bovine GH transgenic mice is maintained mainly
      by a structurally based increase in peripheral vascular resistance.

PMID- 11459774
TI  - Prepro-orexin and orexin receptor mRNAs are differentially expressed in
      peripheral tissues of male and female rats.
AB  - Orexins are produced specifically by neurons located in the lateral hypothalamus.
      Recent results suggested peripheral actions of orexins. Therefore, we analyzed
      the mRNA expression of prepro-orexin and the orexin receptor subtypes OX(1) and
      OX(2) in peripheral rat tissues. Using real-time quantitative RT-PCR we detected
      significant amounts of prepro-orexin mRNA in testis, but not in ovaries. OX(1)
      receptor mRNA was highly expressed in the brain and at lower levels in the
      pituitary gland. Only small amounts of OX(1) receptor mRNA were found in other
      tissues such as kidney, adrenal, thyroid, testis, ovaries, and jejunum. Very high
      levels of OX(2) receptor mRNA, 4-fold higher than in brain, were found in adrenal
      glands of male rats. Low amounts of OX(2) receptor mRNA were present in lung and
      pituitary. In adrenal glands, OX(2) receptor mRNA was localized in the zona
      glomerulosa and reticularis by in situ hybridization, indicating a role in
      adrenal steroid synthesis and/or release. OX(1) receptor mRNA in the pituitary
      and OX(2) receptor mRNA in the adrenal gland were much higher in male than in
      female rats. In the hypothalamus, OX(1) receptor mRNA was slightly elevated in
      female rats. The differential mRNA expression of orexin receptor subtypes in
      peripheral organs indicates discrete peripheral effects of orexins and the
      existence of a peripheral orexin system. This is supported by the detection of
      orexin A in rat plasma. Moreover, the sexually dimorphic expression of OX(1) and
      OX(2) receptors in the hypothalamus, pituitary, and adrenal glands suggests
      gender-specific roles of orexins in the control of endocrine functions.

PMID- 11459775
TI  - PPARalpha and GR differentially down-regulate the expression of nuclear factor
      kappaB-responsive genes in vascular endothelial cells.
AB  - The antiinflammatory action of glucocorticoids is mediated partly by the
      inhibition of the expression of several cytokines and adhesion molecules. Some
      activators for nuclear receptors other than the GR have also been shown to
      inhibit the expression of these inflammatory molecules, although their molecular
      mechanisms remain unidentified. We therefore examined the effects of the
      PPARalpha activator fenofibrate and the GR activator dexamethasone on TNFalpha
      stimulated expression of IL-6 and vascular cell adhesion molecule-1 in vascular
      endothelial cells. Both fenofibrate and dexamethasone reduced TNFalpha-induced IL
      6 production in human vascular endothelial cells, but only fenofibrate reduced
      TNFalpha-stimulated vascular cell adhesion molecule-1 expression in these cells.
      Transient transfection of bovine aortic endothelial cells with an IL-6 promoter
      construct or a vascular cell adhesion molecule-1 promoter construct revealed that
      fenofibrate inhibited TNFalpha-induced IL-6 promoter as well as vascular cell
      adhesion molecule-1 promoter activities, whereas dexamethasone inhibited only the
      former. EMSA demonstrated that both fenofibrate and dexamethasone reduced nuclear
      factor-kappaB binding to its recognition site on the IL-6 promoter, but only
      fenofibrate reduced such binding to the vascular cell adhesion molecule-1
      promoter. Thus, down-regulation of nuclear factor-kappaB activity by PPARalpha
      occurs in both the IL-6 and vascular cell adhesion molecule-1 genes, whereas that
      by GR occurs only in the IL-6 gene in vascular endothelial cells. These results
      strongly suggest the existence of a target gene-specific mechanism for the
      nuclear receptor-mediated down-regulation of nuclear factor-kappaB activity.

PMID- 11459776
TI  - Steroid-independent activation of ER by GnRH in gonadotrope pituitary cells.
AB  - In the rat pituitary gland the mechanism responsible for ERalpha regulation has
      not been fully elucidated. Using transient transfection assays in alphaT3-1
      cells, a cell line of gonadotrope origin, we show that GnRH stimulates estrogen
      response element-containing promoters in an estrogen-independent manner. This
      effect was strictly ER and GnRH receptor dependent, as no activation of the
      reporter gene was observed in presence of the anti-estrogen ICI 182,780 or a GnRH
      antagonist. These data suggest that the GnRH-triggered signaling pathway results
      in 17beta-estradiol-independent trans-activation of the ERalpha in alphaT3-1
      cells. Furthermore, an additive activation was achieved when cells were treated
      with both GnRH and 17beta-estradiol. In primary pituitary cells, GnRH alone (100
      nM) did not cause a significant stimulation of reporter gene activity,
      presumingly due to the low amount of gonadotropes. Interestingly, the combination
      of 17beta-estradiol and GnRH resulted in a significant increase in ERalpha trans
      activation compared with that in cells treated with 17beta-estradiol alone. This
      enhancement was prevented by ICI 182,780, showing an ERalpha requirement.
      Moreover, we show that the effects of GnRH on ERalpha transcriptional activity in
      gonadotrope cell lines are mediated by the PKC/MAPK pathway. In conclusion, our
      data demonstrate that GnRH is an important signal in the regulation of ERalpha
      trans-activation in gonadotrope cells.

PMID- 11459777
TI  - IGF-I as a mediator of VIP/activity-dependent neurotrophic factor-stimulated
      embryonic growth.
AB  - IGF-I and the IGF-I receptor are necessary for normal embryonic growth. VIP is an
      important regulator of early postimplantation growth and acts indirectly through
      the release of other factors, including activity-dependent neurotrophic factor.
      The relationship of IGF-I growth regulation to VIP/activity-dependent
      neurotrophic factor-stimulated growth was examined with whole cultured embryonic
      d 9.5 mouse embryos. Somite numbers and DNA and protein contents were measured in
      embryos treated with IGF-I, anti-IGF-I, VIP, activity-dependent neurotrophic
      factor, and anti-activity-dependent neurotrophic factor-14 (antiserum to an
      activity-dependent neurotrophic factor agonist). IGF-I mRNA content was measured
      after incubation with and without VIP for 30 and 60 min using competitive RT-PCR.
      IGF-I induced a significant, dose-dependent increase in growth as measured by
      somite number, DNA levels, and protein content. Furthermore, anti-IGF-I inhibited
      embryonic growth and also prevented exogenous IGF-mediated growth. Both VIP- and
      activity-dependent neurotrophic factor-stimulated growth were blocked by anti-IGF
      I, whereas anti-activity-dependent neurotrophic factor-14 had no detectable
      effect on IGF-I-induced growth. Treatment with VIP resulted in a 2-fold increase
      in embryonic IGF-I mRNA. These data suggest that IGF-I is a downstream mediator
      of VIP and activity-dependent neurotrophic factor in a regulatory pathway
      coordinating embryonic growth and that VIP may function as a regulator of IGF-I
      gene expression in the embryo.

PMID- 11459778
TI  - Mitogenic and metabolic effects of type I IGF receptor overexpression in insulin
      receptor-deficient hepatocytes.
AB  - We have previously shown that hepatocytes lacking insulin receptors (Ir-/-) fail
      to mediate metabolic responses, such as stimulation of glycogen synthesis, while
      retaining the ability to proliferate in response to IGFs. In this study we have
      asked whether overexpression of type I IGF receptors would rescue the metabolic
      response of Ir-/- hepatocytes. After IGF-I stimulation, insulin receptor
      substrate-1 and -2 phosphorylation and PI3K activity were restored to levels
      similar to or greater than those seen in wild-type cells. Rates of cell
      proliferation in response to IGF-I increased approximately 2-fold, whereas
      glycogen synthesis was restored to wild-type levels, but was comparatively
      smaller than that elicited by overexpression of insulin receptors. In summary,
      overexpression of IGF-I receptors in Ir-/- hepatocytes normalized insulin
      receptor substrate-2 phosphorylation and glycogen synthesis to wild-type levels,
      whereas it increased cell proliferation above wild-type levels. Moreover,
      stimulation of glycogen synthesis was submaximal compared with the effect of
      insulin receptor overexpression. We conclude that IGF-I receptors are more
      efficiently coupled to cell proliferation than insulin receptors, but are less
      potent than insulin receptors in stimulating glycogen synthesis. The data are
      consistent with the possibility that there exist intrinsic signaling differences
      between insulin and IGF-I receptors.

PMID- 11459779
TI  - Ligand-independent activation of pituitary ER: dependence on PKA-stimulated
      pathways.
AB  - In pituitary and other target tissues, estrogen acts through ERs, which are
      ligand-activated nuclear transcription factors. ERs can also be activated by
      intracellular signaling pathways in a ligand-independent manner in some cells.
      Because the pituitary is the target of several cAMP-activating factors, we
      examined the ability of cAMP to activate ERs in the alphaT3 gonadotrope cell
      line. Forskolin, 8-bromo-cAMP, and pituitary adenylate cyclase-activating
      polypeptide all enhanced ER-dependent promoter activity, which was inhibited by
      antiestrogen or a pituitary-specific inhibitory ER variant. Activation was PKA
      dependent and was blocked by the PKA inhibitor H89 or cotransfection of the
      inhibitor PKI. Although cAMP activated MAPK in alphaT3 cells, inhibition of MAPK
      with the MEK inhibitor PD98059 did not prevent forskolin-induced ER activation.
      Similarly, epidermal growth factor did not stimulate ER activity, although it
      increased MAPK activation. Forskolin-induced activation of ER was enhanced by
      cotransfection of steroid receptor coactivator-1 and was inhibited by the
      repressor of ER action, suggesting that cAMP does not alter the normal
      interactions between ER and cofactors. In contrast to results with estrogen, cAMP
      treatment did not decrease ER protein levels. These results demonstrate that in
      the pituitary, cAMP activates ER in a ligand-independent manner exclusively
      through PKA.

PMID- 11459780
TI  - Differential regulation of the human sodium/iodide symporter gene promoter in
      papillary thyroid carcinoma cell lines and normal thyroid cells.
AB  - The absence of TSH-stimulated radioiodide uptake in differentiated thyroid cancer
      is associated with a high recurrence rate and reduced survival. We studied
      regulation of the sodium/iodide symporter gene in human papillary thyroid cancer
      cell lines (BHP) and primary human thyroid cells. BHP cells expressed very low
      levels of sodium/iodide symporter mRNA and did not concentrate iodide, but iodide
      uptake was restored to levels seen in FRTL-5 rat thyroid cells by stable
      transfection of a sodium/iodide symporter cDNA. Sodium/iodide symporter gene
      expression, therefore, was necessary and sufficient for iodide uptake in BHP
      cells. We cloned the human sodium/iodide symporter gene 5'-flanking region and
      analyzed progressive 5'-deletions in transient transfections. We identified a
      region, -596 to -268, essential to confer full promoter activity in primary
      normal human thyroid cells. Sodium/iodide symporter promoter activity in four BHP
      cell lines, however, was markedly reduced, consistent with down-regulation of the
      endogenous sodium/iodide symporter gene. Nuclear extracts from BHP 2-7 cells had
      reduced or absent binding to regions of the sodium/iodide symporter promoter
      shown to be critical for expression, compared with nuclear extracts from FRTL-5
      cells. Competition studies indicated that these nuclear proteins were not known
      thyroid transcription factors. Modifications of the sodium/iodide symporter
      promoter with demethylation or histone acetylation did not increase sodium/iodide
      symporter expression, and no deletions of the critical regulatory region were
      identified in the endogenous gene in BHP cells. Regulation of the sodium/iodide
      symporter 5'-flanking region in transient transfection paralleled endogenous
      sodium/iodide symporter expression. Reduced expression of potential novel nuclear
      factor(s) in these cell lines may contribute to reduced sodium/iodide symporter
      expression resulting in absence of iodide uptake in some papillary thyroid
      cancers.

PMID- 11459781
TI  - Inhibition of ERalpha-mediated trans-activation of human coagulation factor XII
      gene by heteromeric transcription factor NF-Y.
AB  - Human coagulation factor XII promoter contains an estrogen response element that
      mediates ligand-activated ERalpha induction of coagulation factor XII gene
      expression. The 3'-half of coagulation factor XII-estrogen response element
      overlaps a putative CCAAT box, the widespread regulatory element specifically
      recognized by the heteromeric transcription factor NF-Y. Transient cotransfection
      of NF-Y and ERalpha results in strong inhibition of estrogen stimulation of
      coagulation factor XII promoter activity. NF-Y antagonism is primarily exerted by
      the NF-YA subunit and does not require binding to the CCAAT element, as NF-YA
      mutants with impaired DNA binding capacity retain the ability to inhibit ERalpha
      trans-activation. EMSAs with increasing concentrations of recombinant NF-Y do not
      detect the formation of NF-Y-DNA complexes or show impairment of ERalpha binding
      to estrogen response element. Immunoprecipitation of whole cell extracts with
      anti-ERalpha antibody reveals an in vivo association between the two
      transcription factors, which is abolished by deletion of the NF-YA carboxyl
      terminus. In functional experiments with sequential NF-YA deletion mutants the
      HAP2-homology region appears essential in eliciting NF-YA antagonistic activity.
      In conclusion, our results demonstrate that heteromeric transcription factor NF-Y
      inhibits estrogen induction of coagulation factor XII promoter in a DNA binding
      independent fashion and suggest a novel role for NF-Y as a partner for the
      ERalpha transcription complex.

PMID- 11459782
TI  - DNA methylation regulates placental lactogen I gene expression.
AB  - Expression of rat placental lactogen I is specific to the placenta and never
      expressed in other tissues. To obtain insight into the mechanism of tissue
      specific gene expression, we investigated the methylation status in 3.4 kb of the
      5'-flanking region of the rat placental lactogen I gene. We found that the distal
      promoter region of the rat placental lactogen I gene had more potent promoter
      activity than that of the proximal area alone, which contains several possible
      cis-elements. Although there are only 17 CpGs in the promoter region, in vitro
      methylation of the reporter constructs caused severe suppression of reporter
      activity, and CpG sites in the placenta were more hypomethylated than other
      tissues. Coexpression of methyl-CpG-binding protein with reporter constructs
      elicited further suppression of the reporter activity, whereas treatment with
      trichostatin A, an inhibitor of histone deacetylase, reversed the suppression
      caused by methylation. Furthermore, treatment of rat placental lactogen I
      nonexpressing BRL cells with 5-aza-2'-deoxycytidine, an inhibitor of DNA
      methylation, or trichostatin A resulted in the de novo expression of rat
      placental lactogen I. These results provide evidence that change in DNA
      methylation is the fundamental mechanism regulating the tissue-specific
      expression of the rat placental lactogen I gene.

PMID- 11459783
TI  - Sexually dimorphic effects of testosterone on preoptic area calcitonin gene
      related peptide mRNA expression depend upon neuron location and differential
      estrogen and androgen receptor activation.
AB  - Experiments examined activational roles of gonadal steroids on the sexually
      dimorphic, calcitonin gene-related peptide-expressing neurons of the rat preoptic
      area. Gonadectomy of male rats followed by treatment with testosterone,
      dihydrotestosterone, or estrogen demonstrated that the tonic suppressive
      influence of testosterone on cellular levels of calcitonin gene-related peptide
      mRNA expression in the medial preoptic nucleus and anteroventral periventricular
      nucleus occurred through either ER- or AR-mediated mechanisms (P < 0.05). The
      gonadectomy of adult female rats demonstrated little tonic influence of ovarian
      steroids upon calcitonin gene-related peptide mRNA levels. However, the
      administration of male levels of testosterone to ovariectomized rats resulted in
      reduced calcitonin gene-related peptide mRNA expression within the medial
      preoptic nucleus (P < 0.05) and, strikingly, a 3-fold induction in calcitonin
      gene-related peptide mRNA expression in the anteroventral periventricular nucleus
      (P < 0.01). Testosterone's effects in the medial preoptic nucleus and
      anteroventral periventricular nucleus of the female required both ER and AR
      activation. Dual labeling immunocytochemical studies revealed that less than 10%
      of calcitonin gene-related peptide neurons in the male expressed ARs compared
      with approximately 50% in the female. These investigations reveal that sexually
      differentiated region- and steroid receptor-specific mechanisms function in
      association with the sex differences in circulating gonadal steroids to maintain
      the sexually dimorphic nature of calcitonin gene-related peptide expression in
      the preoptic area of the adult rat.

PMID- 11459784
TI  - Relaxin positively regulates matrix metalloproteinase expression in human lower
      uterine segment fibroblasts using a tyrosine kinase signaling pathway.
AB  - Despite the importance of relaxin to normal parturition in various species and
      its potential as an etiological agent in preterm delivery in women, knowledge
      regarding the mechanisms by which relaxin alters cervical connective tissue is
      extremely limited. An established in vitro model for human pregnancy cervix,
      human lower uterine segment fibroblasts, was used to determine the effects of
      relaxin as well as those of progesterone on the expression of matrix
      metalloproteinases and tissue inhibitor of metalloproteinase-1. The results
      demonstrate that relaxin is a positive regulator of matrix metalloproteinase
      expression, as it stimulates the expression of procollagenase protein and mRNA
      levels, stimulates prostromelysin-1 protein and mRNA levels, and inhibits tissue
      inhibitor of metalloproteinase-1 protein expression. Stimulation of
      procollagenase and prostromelysin-1 expression by relaxin does not involve
      phorbol-12-myristate-13-acetate- sensitive PKCs. Relaxin-stimulated tyrosine
      phosphorylation of the putative receptor and inhibition by a receptor tyrosine
      kinase inhibitor suggest that the relaxin receptor is probably a tyrosine kinase
      receptor. Inhibition of c-Raf protein expression using an antisense
      oligonucleotide inhibits relaxin regulation of matrix metalloproteinase and
      tissue inhibitor of metalloproteinase-1, suggesting that a signaling pathway
      involving c-Raf kinase mediates relaxin action.

PMID- 11459785
TI  - Uncoupling protein-3 is a molecular determinant for the regulation of resting
      metabolic rate by thyroid hormone.
AB  - Thyroid hormones increase energy expenditure, partly by reducing metabolic
      efficiency. The control of specific genes at the transcriptional level is thought
      to be the major molecular mechanism. However, both the number and the identity of
      the thyroid hormone-controlled genes remain unknown, as do their relative
      contributions. Uncoupling protein-3, a recently identified member of the
      mitochondrial transporter superfamily and one that is predominantly expressed in
      skeletal muscle, has the potential to be a molecular determinant for thyroid
      thermogenesis. However, changes in mitochondrial proton conductance and resting
      metabolic rate after physiologically mediated changes in uncoupling protein-3
      levels have not been described. Here, in a study on hypothyroid rats given a
      single injection of T(3), we describe a strict correlation in terms of time
      course between the induced increase in uncoupling protein-3 expression (at mRNA
      and protein levels) and decrease in mitochondrial respiratory efficiency, on the
      one hand, and the increase in resting metabolic rate, on the other. First, we
      describe our finding that uncoupling protein-3 is present and regulated by T(3)
      only in metabolically relevant tissues (such as skeletal muscle and heart).
      Second, we follow the time course (at 0, 6, 12, 24, 48, 65, 96, and 144 h) of
      both uncoupling protein-3 mRNA levels and mitochondrial uncoupling protein-3
      density in gastrocnemius muscle and heart. In both tissues, the maximal (12-fold)
      increase in uncoupling protein-3 density was reached at 65 h. The resting
      metabolic rate [lO(2)(kg(0.75))(-1)h(-1)] showed the same time course, and at 65
      h the increase vs. time zero was 45% (1.316 +/- 0.026 vs. 0.940 +/- 0.007; P <
      0.001). At the same time point, gastrocnemius muscle mitochondria showed a
      significantly higher nonphosphorylating respiration rate (nanoatoms of oxygen per
      min/mg protein; increase vs. time zero, 40%; 118 +/- 4 vs. 85 +/- 9; P < 0.05),
      whereas the membrane potential decreased by 8% (168 +/- 2 vs. 182 +/- 4; P <
      0.05). These data are diagnostic of mitochondrial uncoupling. The results
      reported here provide the first direct in vivo evidence that uncoupling protein-3
      has the potential to act as a molecular determinant in the regulation of resting
      metabolic rate by T(3).

PMID- 11459786
TI  - Leptin-deficient mice backcrossed to the BALB/cJ genetic background have reduced
      adiposity, enhanced fertility, normal body temperature, and severe diabetes.
AB  - A deficiency of leptin synthesis in mice results in a complex phenotype
      characterized by morbid obesity, diabetes, sterility, and defective
      thermogenesis. To determine whether the genetic background could alter the
      pleiotropic effects of leptin deficiency, we backcrossed the ob mutation for 10
      generations from the C57BL/6J to the BALB/cJ genetic background. Compared with
      C57BL/6J ob/ob mice, BALB/cJ ob/ob mice showed at 27 wk of age a 35-40% reduction
      in body weight attributed to a 60% decrease in white adipose tissue mass. Food
      intake was not significantly different between the two obese strains, suggesting
      distinct utilization of energy intake. In the fed state, BALB/cJ ob/ob mice had
      elevated insulin and triglycerides levels, demonstrating a worsening effect on
      diabetes. At the reproductive level and in contrast to sterile C57BL/6J ob/ob
      mice, male and female BALB/cJ ob/ob mice were capable of reproducing after a
      mating period of 16 and 32 wk, respectively. At thermoneutrality, the body
      temperature of BALB/cJ ob/ob mice was 2.9 C higher than that of C57BL/6J ob/ob
      mice, whereas exposure of both groups to 4 C demonstrated a prolonged cold
      tolerance of BALB/cJ ob/ob mice. These studies show that the abnormalities caused
      by leptin deficiency can be genetically dissected and separated from each other,
      suggesting discrete pathways controlled by leptin modifier genes.

PMID- 11459787
TI  - Human follistatin-related protein: a structural homologue of follistatin with
      nuclear localization.
AB  - Follistatin-related protein is a recently discovered glycoprotein that is highly
      homologous in both primary sequence and exon/intron domain structure to the
      activin-binding protein, follistatin. We explored their potential for functional
      redundancy by investigating the relative affinities and kinetics of their
      interactions with activin, bone morphogenic protein-6, and bone morphogenic
      protein-7 and by exploring their expression and distribution in human tissues and
      cells. Follistatin and follistatin-related protein mRNA were ubiquitous by
      Northern analyses, although their sites of peak distribution differed, with
      follistatin-related protein and follistatin predominating in the placenta and
      ovary, respectively. Follistatin-related protein, like follistatin,
      preferentially bound activin with high affinity and in an essentially
      irreversible fashion. Although follistatin-related protein, like follistatin,
      possesses a signal sequence and no known nuclear localization signals, its
      secretion was undetectable in most cell lines by RIA. Intriguingly, follistatin
      related protein was identified as a nuclear protein in human granulosa cells and
      all human cell lines tested. Furthermore, Western analyses of CHO cells
      transfected with human follistatin-related protein revealed this protein to
      reside within the insoluble nuclear protein fraction. We conclude that despite
      its remarkably high level of similarity to follistatin with regard to structure
      and activin binding kinetics, follistatin-related protein is a nuclear as well as
      a secretory protein that may perform distinct intracellular actions.

PMID- 11459788
TI  - Regulation of gonadotropin subunit transcription after ovariectomy in the rat:
      measurement of subunit primary transcripts reveals differential roles of GnRH and
      inhibin.
AB  - The aim of this study was to determine if the changes in gonadotropin subunit
      gene expression following ovariectomy reflect transcriptional and/or
      posttranscriptional regulation by GnRH or inhibin. Subunit transcription rates
      were determined by recently developed quantitative RT-PCR for subunit primary
      transcripts (as an indicator of gene transcription), which allow us to measure
      both mRNA and PT from RNA extracted from a single pituitary. Following
      ovariectomy, LHbeta PT concentrations increased 2- to 3-fold between 72 h and 7
      d, paralleling changes in serum LH and LHbeta mRNA. In contrast, serum FSH,
      FSHbeta mRNA, and FSHbeta PT concentrations were 6- to 9-fold greater 12-24 h
      after ovariectomy followed by an additional 2.5-fold increase at 72 h. Although
      alpha RNA was elevated at 72 h after ovariectomy, alpha-primary transcript did
      not change. GnRH antagonist prevented the increase in LHbeta-PT at 72 h, but had
      no effect on the increase in FSHbetaPT at 12 h and was only partially effective
      at 72 h. The acute GnRH-independent increase in FSHbeta-primary transcript after
      ovariectomy could be duplicated by the administration of inhibin antiserum to
      intact rats; inhibin-alpha antiserum did not affect LHbeta-primary transcript,
      but increased FSHbeta-primary transcript concentrations 8- to 11-fold. The half
      disappearance rates of LHbeta and FSHbeta primary transcripts were measured after
      GnRH blockade or administration of recombinant human inhibin A. The half
      disappearance times for LHbeta and FSHbeta primary transcripts following GnRH
      blockade were 13 and 17 min, respectively; the mRNAs did not change. The effects
      of inhibin were specific for FSHbeta; 60 min after inhibin FSHbeta-primary
      transcript was undetectable with a half-disappearance time of 19 min,
      additionally FSHbeta mRNA levels also fell with a half-life of 94 min. In
      conclusion, these data support previous evidence that GnRH regulates gonadotropin
      gene expression primarily at the level of transcription. However, the acute
      increase in FSHbeta-primary transcript after ovariectomy or immunoneutralization
      of inhibin-alpha, and the rapid fall in FSHbeta-primary transcript following rh
      inhibin, provide novel evidence that inhibin suppresses FSHbeta gene
      transcription in addition to its action in regulating FSHbeta mRNA stability.

PMID- 11459789
TI  - Testicular endocrine function in GH receptor gene disrupted mice.
AB  - The consequences of disruption of GH receptor gene in GH receptor knockout mice
      on testicular function were evaluated. Adult male GH receptor knockout mice and
      their normal siblings were divided in to two subgroups and treated with either
      saline or ovine LH (0.3 microg/g BW) in saline. One hour after saline or LH
      administration, blood was obtained via heart puncture. Plasma IGF-I, LH, FSH,
      PRL, androstenedione, and testosterone levels were measured by RIAs. Testicular
      LH and PRL receptor numbers as well as pituitary LHbeta-subunit and testicular
      sulfated glycoprotein-2 mRNA levels were measured. Also, testicular morphometric
      analysis was performed. Unlike in normal, wild-type mice, the circulating IGF-I
      was undetectable in GH receptor knockout mice. The plasma PRL levels were
      (P<0.01) higher in GH receptor knockout mice than in their normal siblings. The
      basal LH secretion was similar in normal and GH receptor knockout mice. However,
      the circulating FSH levels were lower (P<0.001) in GH receptor gene disrupted
      mice. Administration of LH resulted in a significant (P<0.001) increase in plasma
      testosterone levels in both GH receptor knockout and normal mice. However, this
      testosterone response was attenuated (P < 0.01) in GH receptor knockout mice.
      Plasma androstenedione responses were similar in both GH receptor knockout and
      normal mice. Testicular LH and PRL receptor numbers were significantly decreased
      in GH receptor knockout mice. The results of the morphometric analysis of the
      testis revealed that the Leydig cell volume per testis was reduced in mice with
      GH receptor gene disruption. The steady-state of LHbeta-subunit and testicular
      sulfated glycoprotein-2 mRNA levels were not different in GH receptor knockout
      mice relative to their normal siblings. The present in vivo study demonstrates
      that in GH receptor knockout mice, LH action on the testis in terms of
      testosterone secretion is significantly attenuated and suggests that this is due
      to a decrease in the number of testicular LH receptors. The reduced number of PRL
      receptors may contribute to the diminished responsiveness of testicular
      steroidogenesis to LH by decreased ability to convert androstenedione to
      testosterone. These changes are most likely due to the absence of circulating IGF
      I. These findings provide evidence that systemic IGF-I plays a major modulatory
      role in testicular endocrine function.

PMID- 11459790
TI  - The actions of tuberoinfundibular peptide on the hypothalamo-pituitary axes.
AB  - Tuberoinfundibular peptide is a recently discovered agonist for the PTH receptor
      2; the latter has a wide distribution including the external zone of the median
      eminence of the hypothalamus, suggesting a role in neuroendocrine function. We
      have investigated the effects of tuberoinfundibular peptide on the hypothalamo
      pituitary axes in vitro and in vivo. Tuberoinfundibular peptide had effects on
      the hypothalamo-pituitary-adrenal axis with increased release of ACTH-releasing
      factor (tuberoinfundibular peptide 100 nM 4.4 +/- 0.6 pmol/explant vs. control
      2.9 +/- 0.4 pmol/explant, P < 0.001) and increased release of arginine
      vasopressin (tuberoinfundibular peptide 100 nM 563.5 +/- 55.5 fmol/explant vs.
      control 73.4 +/- 9.6 fmol/explant, P < 0.01) from in vitro hypothalamic explants.
      Intracerebroventricular administration of tuberoinfundibular peptide and PTH((1
      34)) resulted in elevated plasma ACTH at 10 min post injection (saline 13.5 +/-
      2.1 pg/ml, tuberoinfundibular peptide 3 nmol 32.3 +/- 4.0 pg/ml; P < 0.01 to
      saline: PTH((1-34)) 10 nmol 28.9 +/- 3.2 pg/ml: P < 0.05 to saline).
      Tuberoinfundibular peptide also had both in vitro and in vivo effects on the
      hypothalamo-pituitary-gonadal axis with increased release of LH-releasing hormone
      (tuberoinfundibular peptide 100 nM 28.5 +/- 5.1 fmol/explant vs. control 19.3 +/-
      2.5 fmol/explant, P < 0.05) from in vitro hypothalamic explants. Both
      intracerebroventricular and peripheral administration of tuberoinfundibular
      peptide had effects on the hypothalamo-pituitary-gonadal axis.
      Intracerebroventricular injection of tuberoinfundibular peptide increased plasma
      LH (tuberoinfundibular peptide 10 nmol 0.70 +/- 0.09 ng/ml vs. saline 0.42 +/-
      0.04 ng/ml at 10 min, P < 0.05). Intraperitoneal administration of
      tuberoinfundibular peptide also increased plasma LH (tuberoinfundibular peptide
      30 nmol 0.53 +/- 0.09 ng/ml vs. saline 0.21 +/- 0.04 ng/ml at 10 min, P < 0.05).
      In addition to these actions on the hypothalamo-pituitary-adrenal and hypothalamo
      pituitary-gonadal axes, an increased release of GH-releasing factor (GRF) from
      hypothalamic explants (tuberoinfundibular peptide 100 nM 770.9 +/- 90.7
      pg/explant vs. control 657.8 +/- 77.7 pg/explant, P < 0.01) was observed.
      Overall, these data show the actions of tuberoinfundibular peptide on the
      hypothalamo-pituitary axes and suggest that it may play a role in the control of
      the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes.

PMID- 11459791
TI  - Evidence of an orexigenic role for cocaine- and amphetamine-regulated transcript
      after administration into discrete hypothalamic nuclei.
AB  - Cocaine- and amphetamine-regulated transcript is expressed in hypothalamic
      regions involved in the central control of food intake. Previous data have
      implicated cocaine- and amphetamine-regulated transcript as an anorectic peptide.
      We studied the effect of the active fragment of cocaine- and amphetamine
      regulated transcript, cocaine- and amphetamine-regulated transcript-(55-102), on
      feeding when injected into discrete nuclei of the hypothalamus. Cocaine- and
      amphetamine-regulated transcript-(55-102) (0.04 nmol) elicited a delayed, but
      significant, increase in feeding in 24-h fasted rats after injection into the
      ventromedial nucleus (1-2 h, 261 +/- 60% of control; P < 0.05) and arcuate
      nucleus (1-2 h, 225 +/- 38% of control; P < 0.05) of the hypothalamus.
      Administration of a higher dose of cocaine- and amphetamine-regulated transcript
      (55-102) (0.2 nmol) elicited a significant increase in feeding after injection
      into the ventromedial nucleus (1-2 h, 1253 +/- 179% of control; P < 0.001),
      arcuate nucleus (1-2 h, 265 +/- 43% of control; P < 0.05), paraventricular
      nucleus (2-4 h food intake, 186 +/- 29% of control; P < 0.05), lateral
      hypothalamic area (2-4 h, 280 +/- 34% of control; P < 0.001), anterior
      hypothalamic area (2-4 h, 252 +/- 42% of control; P < 0.01), dorsomedial nucleus
      (2-4 h, 368 +/- 29% of control;P < 0.001) and supraoptic nucleus (2-4 h, 212 +/-
      34% of control; P < 0.05) of the hypothalamus. Administration of cocaine- and
      amphetamine-regulated transcript-(55-102) into the third ventricle of the
      hypothalamus resulted in an inhibition in feeding [0-4 h (0.4 nmol), 33 +/- 13%
      control; P < 0.001], but was associated with marked abnormalities in behavior,
      which may have interfered with feeding. These behavioral abnormalities were not
      observed after the administration of cocaine- and amphetamine-regulated
      transcript-(55-102) directly into the arcuate nucleus. These data suggest that
      cocaine- and amphetamine-regulated transcript may play an orexigenic role in the
      hypothalamic feeding circuitry.

PMID- 11459792
TI  - PGE(2) is essential for gap junction-mediated intercellular communication between
      osteocyte-like MLO-Y4 cells in response to mechanical strain.
AB  - We have observed, in our previous studies, that fluid flow increases gap junction
      mediated intercellular coupling and the expression of a gap junction protein,
      connexin 43, in osteocyte-like MLO-Y4 cells. Interestingly, this stimulation is
      further enhanced during the poststress period, indicating that a released
      factor(s) is likely to be involved. Here, we report that the conditioned medium
      obtained from the fluid flow-treated MLO-Y4 cells increased the number of
      functional gap junctions and connexin 43 protein. These changes are similar to
      those observed in MLO-Y4 cells directly exposed to fluid flow. Fluid flow was
      found to induce PGE(2) release and increase cyclooxygenase 2 expression.
      Treatment of the cells with PGE(2) had the same effect as fluid flow, suggesting
      that PGE(2) could be responsible for these autocrine effects. When PGE(2) was
      depleted from the fluid flow-conditioned medium, the stimulatory effect on gap
      junctions was partially, but significantly, decreased. Addition of the
      cyclooxygenase inhibitor, indomethacin, partially blocked the stimulatory effects
      of mechanical strain on gap junctions. Taken together, these studies suggest that
      the stimulatory effect of fluid flow on gap junctions is mediated, in part, by
      the release of PGE(2). Hence, PGE(2) is an essential mediator between mechanical
      strain and gap junctions in osteocyte-like cells.

PMID- 11459793
TI  - Insulin- and glucose-induced phosphorylation of the Na(+),K(+)-adenosine
      triphosphatase alpha-subunits in rat skeletal muscle.
AB  - Phosphorylation of the alpha-subunits of Na(+),K(+)-adenosine triphosphatase in
      response to insulin, high extracellular glucose concentration, and phorbol 12
      myristate 13-acetate was investigated in isolated rat soleus muscle. All three
      stimuli increased alpha-subunit phosphorylation approximately 3-fold. Phorbol 12
      myristate 13-acetate- and high glucose-induced phosphorylation of the alpha
      subunit was completely abolished by the PKC inhibitor GF109203X, whereas insulin
      stimulated phosphorylation was only partially reduced. Notably, insulin
      stimulation resulted in phosphorylation of the alpha-subunit on serine,
      threonine, and tyrosine residues, whereas high extracellular glucose or phorbol
      12-myristate 13-acetate stimulation mediated phosphorylation only on serine and
      threonine residues. Insulin stimulation resulted in translocation of Na(+),K(+)
      adenosine triphosphatase alpha(2)-subunit to the plasma membrane and increased
      Na(+),K(+)-adenosine triphosphatase activity in the same membrane fraction. High
      glucose had no effect on alpha-subunits distribution. Immunoprecipitation with
      antiphosphotyrosine antibody and subsequent Western blot analysis with anti
      alpha(1)- and -alpha(2)-subunit antibodies revealed that both alpha(1)- and
      alpha(2)-subunit isoforms underwent phosphorylation on tyrosine residues in
      response to insulin, although with different time course and magnitude. Thus, we
      show that insulin-stimulated phosphorylation of Na(+),K(+)-adenosine
      triphosphatase alpha-subunit occurs via a PKC- and tyrosine kinase-dependent
      mechanism, whereas high glucose-induced phosphorylation is only PKC-dependent.
      Phosphorylation of Na(+),K(+)-adenosine triphosphatase alpha-subunits may be
      involved in regulation of Na(+),K(+)-adenosine triphosphatase activity by insulin
      or high extracellular glucose in skeletal muscle.

PMID- 11459794
TI  - Transcriptional regulation of the human GnRH II gene is mediated by a putative
      cAMP response element.
AB  - Human neuronal medulloblastoma cells (TE-671) were recently demonstrated to
      express the two forms of GnRH (GnRH-I and GnRH-II). We have used this cell line
      as a model system to demonstrate regulation of the human GnRH-II gene by cAMP. RT
      PCR and Southern hybridization demonstrated that GnRH-II mRNA is strongly up
      regulated ( approximately 6-fold) by (Bu)(2)cAMP. The concentration of GnRH-II
      that was released into the medium of TE-671 cells treated with the cAMP analog
      was significantly higher than that of the untreated cells. TE-671 cells that were
      stimulated by (Bu)(2)cAMP demonstrated morphological changes and strong
      immunoreactive GnRH-II staining in part of the cell population. After screening
      of the GnRH-II promoter sequence, we identified a putative cAMP response element
      consensus site. The GnRH-I and GnRH-II promoters were isolated by PCR using human
      genomic DNA and cloned into the luciferase reporter plasmid. By measuring the
      basal activity of the promoters that were transfected to TE-671 cells, we found a
      much stronger basal activity of the GnRH-II promoter compared with that of GnRH
      I. Treatment of transfected TE-671 cells with (Bu)(2)cAMP resulted in a strong
      activation of the GnRH-II promoter compared with a modest activation of the GnRH
      I promoter. To determine the functionality of this putative cAMP response element
      site, we mutated this site. TE-671 cells that were transfected with cAMP response
      element mutant constructs demonstrated a diminished basal activity of the GnRH-II
      promoter. Treatment of the transfected cells with the cAMP analog demonstrated a
      decrease to 0.03% of the activity of the mutated promoter compared with that of
      the wild type. These results clearly demonstrate the importance of the putative
      cAMP response element site for the basal activity as well as for induction of the
      GnRH-II promoter by cAMP.

PMID- 11459795
TI  - Regulation of prothymosin alpha gene expression by estrogen in estrogen receptor
      containing breast cancer cells via upstream half-palindromic estrogen response
      element motifs.
AB  - Prothymosin alpha (PTalpha), a protein associated with cell proliferation and
      chromatin remodeling, and found to selectively enhance ER transcriptional
      activity by interacting with a repressor of ER activity, is shown to be a primary
      response gene to estrogen. Prothymosin alpha mRNA was rapidly increased by
      estrogen, followed by a 6-fold increase in prothymosin alpha protein content in
      ER-containing breast cancer cells. Analysis of the prothymosin alpha promoter and
      5'-flanking region, and electrophoretic gel mobility shift studies showed the
      strong inducibility by the estradiol-ER complex to be mediated by two consensus
      half-palindromic estrogen response elements at -750 and -1051, which directly
      bind the ER. Estrogenic stimulation of prothymosin alpha required a DNA binding
      form of ER with a functional activation function-2 domain. The prothymosin alpha
      5'-regulatory region also contains multiple Sp1 sites. Although addition of Sp1
      did not further enhance estradiol-ER stimulated prothymosin alpha transcriptional
      activity in breast cancer cells, transfection and response element mutagenesis
      studies using Drosophila cells, which are deficient in Sp1, revealed that Sp1 and
      the estradiol occupied-ER can each activate the prothymosin alpha gene
      independently of the other and act in an additive manner. These observations,
      documenting robust prothymosin alpha up-regulation by the estradiol-ER complex
      via widely spaced half-palindromic estrogen response element motifs, are
      reminiscent of those shown previously for the ovalbumin gene and suggest that the
      use of multiple half response elements may be a more common mode for regulation
      of gene expression by the ER than previously appreciated. In addition, these
      observations suggest interrelationships between cell proliferation and gene
      transcriptional activities and indicate a positive mechanism by which PTalpha,
      which increases ER transcriptional effectiveness, is itself up-regulated by the
      estrogen-ER complex.

PMID- 11459796
TI  - Characterization of signal transduction pathway in neurotropic action of
      angiotensin II in brain neurons.
AB  - Interaction of angiotensin II with the neuronal angiotensin type 1 receptor
      stimulates the PI3K signaling pathway. Our objective in this study was to
      investigate the hypothesis that the PI3K cascade regulates the neurotropic
      actions of angiotensin II in rat brain neurons. We followed growth associated
      protein-43 expression and neurite extension as markers of neurotropic activity.
      Angiotensin II, through its interaction with the angiotensin type 1 receptor,
      increased growth associated protein-43 expression and neurite extension. These
      effects were abolished by pretreatment of neurons with wortmannin and rapamycin,
      but not by PD 98059. Antisense oligonucleotides specific for p70(S6) kinase also
      inhibited angiotensin II-stimulated neurotropic activity. These data confirm the
      involvement of PI3K and p70(S6) kinase in angiotensin II-mediated neurotropic
      action. Further support for this was provided by the observation that angiotensin
      II caused a time-dependent stimulation of p70(S6) kinase by an angiotensin type 1
      receptor-mediated process. We also found that the neurotropic actions of
      angiotensin II are mediated by plasminogen activator inhibitor-1. Evidence for
      this includes 1) angiotensin II-stimulated neuronal plasminogen activator
      inhibitor-1 gene expression, 2) potent neurotropic action of exogenous
      plasminogen activator inhibitor-1, and 3) inhibitory neurotropic effect of
      angiotensin II by antisense oligonucleotide-mediated depletion of plasminogen
      activator inhibitor-1. Finally, we found that the neurotropic action of
      plasminogen activator inhibitor-1 is not blocked by either angiotensin type 1
      receptor antagonist or inhibitors of PI3K or p70(S6) kinase, indicating that the
      plasminogen activator inhibitor-1 step is downstream from the p70(S6) kinase.
      These observations demonstrate that angiotensin II is a neurotropic hormone that
      engages a distinct PI3K-p70(S6) kinase-plasminogen activator inhibitor-1
      signaling pathway for this action.

PMID- 11459797
TI  - Male reproductive phenotypes in double mutant mice lacking both FSHbeta and
      activin receptor IIA.
AB  - Activins are known to signal through two serine/threonine kinase type II
      receptors. Activin receptor IIA is widely expressed in the male reproductive
      axis, including the pituitary and testis. Our previous studies using gene
      knockout mice have confirmed the essential in vivo role of activin receptor IIA
      in FSH homeostasis. Activin receptor IIA-null male mice are fertile, have
      suppressed pituitary and serum FSH levels, and demonstrate a decrease in testis
      size as a result of reduced Sertoli cells and germ cells. Similarly, FSHbeta null
      male mice are fertile despite reduced testis size and Sertoli cell number. To
      define the direct roles of activin receptor IIA signaling locally in the testis,
      independent of its effects on FSH homeostasis, we generated double mutant mice
      lacking both activin receptor IIA and FSH by a genetic intercross and analyzed
      the male reproductive phenotypes. The double mutant male mice lacking both FSH
      and activin receptor IIA are fertile, demonstrate no significant reduction in
      testis size, and produce small litters compared with mice lacking either FSH or
      activin receptor IIA alone. Histological analyses of the testes from double
      mutant mice revealed the presence of normal stages of spermatogenesis. However,
      there was a significant reduction in the epididymal sperm number compared with
      that of the individual mutants. Northern blot analyses of total RNA from testes
      of double mutants did not reveal transcriptional up-regulation of activin
      receptor IIB, the other activin type II receptor. Although RNA expression
      profiles of many testis cell-specific markers are unaltered, stereological
      analysis of the testes from double mutants indicates that there was a reduction
      in type A and I spermatogonial number compared with that observed in individual
      mutants. Our results provide in vivo genetic evidence to demonstrate that activin
      receptor IIA signaling plays an important local role within the testis,
      independent of its actions via FSH homeostasis in the pituitary.

PMID- 11459798
TI  - Divergent immune responses in male and female mice after trauma-hemorrhage:
      dimorphic alterations in T lymphocyte steroidogenic enzyme activities.
AB  - Immune responses are suppressed in males, but not in proestrous females, after
      trauma-hemorrhage. Testosterone and 17beta-estradiol appear to be responsible for
      divergent immune effects. There is considerable evidence to suggest sex steroid
      hormone involvement in immune functions. As formation of active steroid depends
      on the activity of androgen- and estrogen-synthesizing enzymes, expression and
      activity of 5alpha-reductase, aromatase, and 3beta- and 17beta- hydroxysteroid
      dehydrogenases were determined in spleen and T lymphocytes of male and proestrous
      female mice after trauma-hemorrhage. All of the enzymes were present in spleen,
      specifically in T lymphocytes. 5alpha-Reductase expression and activity increased
      in male T lymphocytes, whereas aromatase activity, but not expression, increased
      in female T lymphocytes. Increased 5alpha-reductase activity in male T
      lymphocytes is immunosuppressive because of increased 5alpha-dihydrotestosterone
      synthesis, whereas in females increased aromatase activity triggering 17beta
      estradiol synthesis is immunoprotective. This study also demonstrates the
      importance of 17beta-hydroxysteroid dehydrogenase oxidative and reductive
      functions. The immunoprotection of proestrous females is associated with enhanced
      reductase function of the enzyme. In males, decreased expression of oxidative
      isomer type IV, which impairs catabolism of 5alpha-dihydrotestosterone, probably
      augments immunosuppression. This study provides evidence for the involvement of
      intracrine sex steroid synthesis in gender dimorphic immune responses after
      trauma-hemorrhage.

PMID- 11459799
TI  - Naked TSH receptor DNA vaccination: A TH1 T cell response in which interferon
      gamma production, rather than antibody, dominates the immune response in mice.
AB  - Two approaches have been developed to induce TSH receptor antibodies in mice with
      properties resembling those in Graves' disease, the Shimojo model of injecting
      live fibroblasts coexpressing the TSH receptor and major histocompatibility
      complex antigen Class II, and TSH receptor-DNA vaccination. Thyroid-stimulating
      antibodies appear to occur less commonly after DNA vaccination, but there has
      been no direct comparison of these models. We performed a three-way comparison of
      1) AKR/N and 2) BALB/c mice vaccinated with TSH receptor-DNA and 3) AKR/N mice
      injected with fibroblasts expressing the TSH receptor and the major
      histocompatibility complex antigen class II of AKR/N mice. TSH receptor-DNA
      vaccinated mice had low or undetectable levels of TSH receptor antibodies
      determined by ELISA or flow cytometry. Nonspecific binding precluded comparisons
      with sera from Shimojo mice by these assays. TSH binding inhibition and thyroid
      stimulating antibody were undetectable in TSH receptor-DNA vaccinated mice. In
      Shimojo mice, TSH binding inhibition was positive in approximately 60%, and
      thyroid-stimulating antibodies were positive in hyperthyroid animals. Unlike the
      negative antibody data, splenocytes from TSH receptor-vaccinated (but not
      Shimojo) mice proliferated and produced the Th1 cytokine interferon-gamma in
      response to TSH receptor antigen. In conclusion, DNA vaccination is less
      effective at inducing TSH receptor antibodies than the Shimojo approach, but it
      permits the future characterization of TSH receptor-specific T cells generated
      without adjuvant.

PMID- 11459800
TI  - IL-1alpha and TNFalpha down-regulate CRH receptor-2 mRNA expression in the mouse
      heart.
AB  - Two receptors (CRH receptor type 1 and CRH receptor type 2) have been identified
      for the stress-induced neuropeptide, CRH and related peptides, urocortin, and
      urocortin II. We previously found marked down-regulation of cardiac CRH receptor
      type 2 expression following administration of bacterial endotoxin,
      lipopolysaccharide, a model of systemic immune activation, and inflammation. We
      postulated that inflammatory cytokines may regulate CRH receptor type 2. We show
      that systemic IL-1alpha administration significantly down-regulates CRH receptor
      type 2 mRNA in mouse heart. In addition, TNFalpha treatment also reduces CRH
      receptor type 2 mRNA expression, although the effect was not as marked as with IL
      1alpha. However, CRH receptor type 2 mRNA expression is not altered in adult
      mouse ventricular cardiomyocytes stimulated in vitro with TNFalpha or IL-1alpha.
      Thus, cytokine regulation may be indirect. Exogenous administration of
      corticosterone in vivo or acute restraint stress also reduces cardiac CRH
      receptor type 2 mRNA expression, but like cytokines, in vitro corticosterone
      treatment does not modulate expression in cardiomyocytes. Interestingly,
      treatment with urocortin significantly decreases CRH receptor type 2 mRNA in
      cultured cardiomyocytes. We speculate that in vivo, inflammatory mediators such
      as lipopolysaccharide and/or cytokines may increase urocortin, which in turn down
      regulates CRH receptor type 2 expression in the heart. Because CRH and urocortin
      increase cardiac contractility and coronary blood flow, impaired CRH receptor
      type 2 function during systemic inflammation may ultimately diminish the adaptive
      cardiac response to adverse conditions.

PMID- 11459801
TI  - Leptin reduces ovariectomy-induced bone loss in rats.
AB  - Bone mineral density increases with fat body mass, and obesity has a protective
      effect against osteoporosis. However, the relationship between fat body mass and
      bone mineral density is only partially explained by a combination of hormonal and
      mechanical factors. Serum leptin levels are strongly and directly related to fat
      body mass. We report here the effects of leptin administration compared with
      estrogen therapy on ovariectomy-induced bone loss in rats. Leptin was effective
      at reducing trabecular bone loss, trabecular architectural changes, and
      periosteal bone formation. Interestingly, the combination of estrogen and leptin
      further decreased bone turnover compared with that in estrogen-treated
      ovariectomized rats. Leptin also significantly increased osteoprotegerin mRNA
      steady state levels and protein secretion and decreased RANK ligand mRNA levels
      in human marrow stromal cells in vitro. Our findings suggest that leptin could
      modulate bone remodeling in favor of a better bone balance in rats. This study is
      the first evidence that leptin therapy has a significant effect in preventing
      ovariectomy-induced bone loss, and this effect may at least in part be mediated
      by the osteoprotegerin/RANK ligand pathway.

PMID- 11459802
TI  - PPARalpha-dependent induction of liver microsomal esterification of estradiol and
      testosterone by a prototypical peroxisome proliferator.
AB  - Fatty acyl-coenzyme A:estradiol acyltransferase in liver microsomes catalyzes the
      formation of estradiol fatty acid esters. These estrogen esters are extremely
      lipophilic and have prolonged hormonal activity because they are slowly
      metabolized and slowly release estradiol. Our previous studies showed that
      treatment of female rats with clofibrate or gemfibrozil (peroxisome proliferators
      commonly used as hypolipidemic drugs) markedly stimulated the liver microsomal
      esterification of estradiol. Although clofibrate administration is a potent
      inducer of liver microsomal fatty acyl-coenzyme A:estradiol acyltransferase in
      rats, it is a poor inducer in mice. In contrast to these observations, Wy-14,643
      (an exceptionally potent prototypical peroxisome proliferator) is a strong
      inducer of fatty acyl-coenzyme A:estradiol acyltransferase in mice. To explore
      the role of PPARalpha in the induction of fatty acyl-coenzyme A:estradiol
      acyltransferase and fatty acyl-coenzyme A:testosterone acyltransferase activities
      by peroxisome proliferators, we fed 0.1% Wy-14,643 to female wild-type and
      PPARalpha null mice for 11 d. The liver microsomal acyl-coenzyme A:estradiol
      acyltransferase and acyl-coenzyme A:testosterone acyltransferase activities were
      increased 4- to 5-fold in wild-type mice fed Wy-14,643, but no increase was
      observed in null mice. These results demonstrate that induction of acyl-coenzyme
      A:estradiol acyltransferase and acyl-coenzyme A:testosterone acyltransferase
      activities by a prototypical peroxisome proliferator is dependent on PPARalpha.

PMID- 11459803
TI  - The effects of insulin, glucose, and pyruvate on the kinetics of leptin
      secretion.
AB  - Leptin is a hormone that is secreted by fat cells and has roles in body weight
      regulation, glucose metabolism, reproduction, and other neuroendocrine functions.
      The purpose of this study was to determine whether the secretagogues, insulin,
      glucose, and pyruvate, enhance leptin secretion by increasing leptin synthesis,
      or whether these secretagogues stimulate the quantal release of a stored
      cytosolic pool of leptin. We found that in the absence of secretagogues, the rate
      of leptin secretion from isolated rat adipocytes approximately equals the rate of
      leptin synthesis. For 60 min after the addition of secretagogues, leptin
      synthesis rapidly increases, with little or no leptin secretion; leptin increases
      intracellularly by approximately 60% (P < 0.05). After 60 min, leptin is
      significantly released from cells. At 120 and 240 min, secretagogues enhance
      leptin secretion into the medium by 35% (P < 0.05) and 40% (P < 0.01),
      respectively. Cycloheximide prevents the synthesis and the secretagogue-mediated
      secretion of leptin. Monensin, an inhibitor of protein translocation, has no
      effect on leptin synthesis, but it blocks the secretagogue-mediated secretion of
      leptin. These findings suggest that secretagogues enhance leptin release by
      increasing leptin synthesis, rather than by enhancing the release of a
      preexisting cytosolic pool of leptin.

PMID- 11459804
TI  - Calcitonin induces IL-6 production via both PKA and PKC pathways in the pituitary
      folliculo-stellate cell line.
AB  - It has been demonstrated that calcitonin-binding sites are present in a variety
      of tissue types, including in the pituitary gland. Interleukin-6 (IL-6) is also
      produced in the pituitary and it regulates the secretion of various hormones. In
      this study, we examined the expression of the calcitonin receptor and the
      mechanism of IL-6 production induced by calcitonin in the pituitary folliculo
      stellate cell line (TtT/GF). The mRNA of calcitonin receptor subtype C1a, but not
      that of C1b, was detected by RT-PCR in TtT/GF cells and in the normal mouse
      pituitary. Calcitonin increased cAMP accumulation and IL-6 production in a
      concentration-dependent manner in TtT/GF cells. As calcitonin activates the PKA
      and PKC pathways, we investigated the contributions of PKA and PKC to IL-6
      production. IL-6 production was only slightly increased by either 8-bromo-cAMP (1
      mM) or phorbol 12-myristate 13-acetate (100 nM) alone. However, IL-6 was
      synergistically induced in the presence of both 8-bromo-cAMP (1 mM) and phorbol
      12myristate 13-acetate (100 nM). Furthermore, calcitonin-induced IL-6 production
      was completely suppressed by H-89 (PKA inhibitor) or GF109203X (PKC inhibitor),
      indicating that the activation of both PKA and PKC is necessary for calcitonin
      induced IL-6 production. On the other hand, pertussis toxin (G(i)/G(o) signaling
      inhibitor) treatment achieved an approximately 9-fold increase in calcitonin
      induced IL-6 production. These results show that calcitonin-stimulated IL-6
      production is mediated via both PKA- and PKC-signaling pathways, whereas
      calcitonin also suppresses IL-6 production by activating G(i)/G(o) proteins in
      folliculo-stellate cells.

PMID- 11459805
TI  - RIP 140 modulates transcription of the steroidogenic acute regulatory protein
      gene through interactions with both SF-1 and DAX-1.
AB  - Coregulators have been suggested to act as a bridging apparatus between nuclear
      receptors and the transcriptional machinery. The orphan receptor SF-1 plays a
      role in controlling the basal and cAMP-stimulated expression of the human
      steroidogenic acute regulatory protein gene. DAX-1 is the gene responsible for X
      linked adrenal hypoplasia congenita and blocks steroid biosynthesis by impairing
      the expression of steroidogenic acute regulatory protein. In the present study we
      examined the role of coregulators in the actions of SF-1 and DAX-1 on the human
      steroidogenic acute regulatory protein promoter. We found that the coregulator
      RIP 140 interacts with SF-1 in the yeast two-hybrid system. Glutathione-S
      transferase pull-down assays and coimmunoprecipitations confirmed the interaction
      between RIP 140 and SF-1. RIP 140 was also shown to interact with DAX-1. When an
      RIP 140 expression vector was introduced into Y-1 cells, basal and cAMP
      stimulated human steroidogenic acute regulatory protein promoter activities
      decreased. The inhibitory effect of RIP 140 on human steroidogenic acute
      regulatory protein promoter activity was dependent upon the presence of SF-1. The
      cAMP response of an SF-1 response element was inhibited by both RIP 140 and DAX-1
      expression vectors at low concentrations of plasmids. We conclude that RIP 140
      binds to the orphan nuclear receptor SF-1 and DAX-1 and modulates their actions
      on the human steroidogenic acute regulatory protein promoter.

PMID- 11459806
TI  - Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat
      brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis.
AB  - Neurosteroidogenesis has not been well elucidated due to the very low level of
      steroidogenic proteins in the brain. Here we report the first demonstration of
      the neuronal localization of neurosteroidogenic systems as well as the regulation
      of neurosteroidogenic activity in the adult rat hippocampus. Significant
      localization of cytochrome P450scc was observed in pyramidal neurons and granule
      neurons by means of immunohistochemical staining of slices. We also observed the
      colocalization, in hippocampal neurons, of P450scc with redox partners,
      hydroxysteroid sulfotransferase and steroidogenic acute regulatory protein. The
      distributions of astroglial cells and oligodendroglial cells showed very
      different patterns from that of the P450scc-containing cells. The expression of
      P450scc, redox partners, the sulfotransferase, and steroidogenic acute regulatory
      protein was also confirmed by Western blot analysis. The process of active
      neurosteroidogenesis was stimulated by exposing neurons to N-methyl-D-aspartate.
      Upon stimulation with N-methyl-D-aspartate, Ca(2+) influx through the N-methyl-D
      aspartate subtype of glutamate receptors occurred, and significant net production
      of pregnenolone and pregnenolone sulfate was observed in the hippocampus. This
      neurosteroid production was considerably suppressed by the addition of
      antagonists of N-methyl-D-aspartate receptors, by Ca(2+) depletion, or by the
      addition of an inhibitor of P450scc. Upon stimulation with N-methyl-D-aspartate,
      the processing of full-length steroidogenic acute regulatory protein (37-kDa) to
      the truncated 30-kDa steroidogenic acute regulatory protein was observed. Taken
      together, these observations imply that hippocampal neurons synthesize
      neurosteroids. This synthesis may be stimulated and regulated by glutamate
      mediated synaptic communication.

PMID- 11459807
TI  - Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human
      granulosa cells.
AB  - Obesity is associated with insulin resistance and some reproductive
      abnormalities. Circulating FFAs are often elevated in obese subjects and are also
      closely linked to insulin resistance. In this study, we demonstrated that
      saturated FFAs, such as palmitic acid and stearic acid, markedly suppressed the
      granulosa cell survival in a time- and dose-dependent manner. Polyunsaturated
      FFA, arachidonic acid, had no effect on the cell survival, even at
      supraphysiological concentrations. The suppressive effect of saturated FFAs on
      cell survival was caused by apoptosis, as evidenced by DNA ladder formation and
      annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effects of
      palmitic acid and stearic acid were unrelated to the increase of ceramide
      generation or nitric oxide production and were also completely blocked by
      Triacsin C, an inhibitor of acylcoenzyme A synthetase. In addition, acylcoenzyme
      A, pamitoylcoenzyme A, and stearylcoenzyme A markedly suppressed granulosa cell
      survival, whereas arachidonoylcoenzyme A had no such effect, and this finding was
      consistent with the effect of the respective FFA form. Surprisingly, arachidonic
      acid instead showed a protective effect on palmitic acid- and stearic acid
      induced cell apoptosis. A Western blot analysis showed the apoptosis of the
      granulosa cells induced by palmitic acid to be accompanied by the down-regulation
      of an apoptosis inhibitor, Bcl-2, and the up-regulation of an apoptosis effector,
      Bax. These results indicate that saturated FFAs induce apoptosis in human
      granulosa cells caused by the metabolism of the respective acylcoenzyme A form,
      and the actual composition of circulating FFAs may thus play a critical role in
      the apoptotic events of human granulosa cells. These effects of FFAs on granulosa
      cell survival may be a possible mechanism for reproductive abnormalities, such as
      amenorrhea, which is frequently observed in obese women.

PMID- 11459808
TI  - Targeted overexpression of IGF-I in smooth muscle cells of transgenic mice
      enhances neointimal formation through increased proliferation and cell migration
      after intraarterial injury.
AB  - The response of arterial smooth muscle cells to injury is governed by a complex
      series of events. Significant among them is the paracrine production of peptide
      growth factors. To determine the impact of local IGF-I gene expression on
      vascular injury, the left carotid arteries of SMP8-IGF-I mice (in which IGF-I is
      selectively overexpressed in smooth muscle cells by means of a smooth muscle
      alpha-actin promoter) and wild-type controls were injured mechanically with an
      epon resin probe. After 7 and 14 d, a progressive increase in medial area was
      seen in both SMP8-IGF-I and wild-type mice, but they were not significantly
      different from each other. However, by 14 d there was a more than 4-fold increase
      in neointimal area in transgenic vs. wild-type. The intima/media ratios were also
      strikingly increased at 14 d in the IGF-I-overexpressing animals. The mitotic
      index, determined in animals injected daily with bromodeoxyuridine for 3 d before
      death, was markedly elevated in both the media and neointima 7 d after injury in
      SMP8-IGF-I mice, but the effect had subsided by 14 d. Despite a higher rate of
      cell division, the relative increase in medial area was less in the SMP8-IGF-I
      mice than in wild-type mice at both 7 and 14 d, consistent with a stimulation of
      cell migration to the neointima. The experiments reported here provide compelling
      evidence that paracrine expression of IGF-I is a powerful stimulus for smooth
      muscle cell proliferation and migration in vivo.

PMID- 11459809
TI  - Cloning and characterization of a novel pregnancy-induced growth inhibitor in
      mammary gland.
AB  - Growth factors and growth inhibitors play crucial roles in the growth regulation
      and differentiation of mammary epithelial cells. Studies have shown that during
      pregnancy, with the onset of terminal differentiation, there is a dramatic
      decrease in the proliferation of the mammary epithelial cells. Here we report the
      cloning and characterization of a novel pregnancy-induced cDNA, OKL38, from a
      human ovarian cDNA library. This cDNA encodes for a protein of approximately 34.5
      kDa. Tissue distribution studies through Northern analyses revealed the
      ubiquitous nature of OKL38 transcripts in most tissues, with the highest levels
      observed in the ovary, kidney, and liver. The onset and advancement of pregnancy
      also gave rise to a concomitant increase in OKL38 gene expression. In situ
      hybridization revealed that OKL38 mRNA was further detected in mammary secretory
      epithelial cells. However, low levels of OKL38 transcripts were observed in the
      various human breast cancer cell lines studied and were barely detectable in all
      dimethylbenz(A)anthracene-induced mammary tumors examined. Transfection studies
      with OKL38 cDNA with MCF-7 cells resulted in growth inhibition in vitro and
      reduction in tumor formation in vivo. These observations led to speculation that
      OKL38 may play a vital role in the growth regulation and differentiation of
      breast epithelial cells during pregnancy and its implications in tumorigenesis.

PMID- 11459810
TI  - Disease progression in chronic relapsing experimental allergic encephalomyelitis
      is associated with reduced inflammation-driven production of corticosterone.
AB  - In this study, we demonstrate that disruption of neuroendocrine signaling is a
      major factor driving disease progression in myelin oligodendrocyte glycoprotein
      induced chronic relapsing experimental autoimmune encephalomyelitis, an animal
      model of multiple sclerosis. Although the initial episode of chronic relapsing
      experimental autoimmune encephalomyelitis is associated with a robust
      hypothalamic-pituitary-adrenocortical axis response, we show that subsequent
      disease progression is associated with a selective desensitization of
      hypothalamic-pituitary-adrenocortical responsiveness to inflammatory mediators.
      Inflammatory activity in the central nervous system during relapse is therefore
      unable to produce an endogenous immunosuppressive corticosterone response, and
      disease progresses into an ultimately lethal phase. However, disease progression
      is inhibited if the circulating corticosterone level is maintained at levels seen
      during the initial phase of disease. The effect of hypothalamic-pituitary
      adrenocortical axis desensitization on the clinical course of experimental
      autoimmune encephalomyelitis is aggravated by a marked reduction in
      proinflammatory cytokine synthesis in the central nervous system in the later
      stages of disease, reflecting an increasing involvement of antibody, rather than
      T cell-dependent effector mechanisms, in disease pathogenesis, with time. Thus,
      our data indicate that distinct immune-endocrine effects play a decisive role in
      determining disease progression in multiple sclerosis, a concept supported by
      reports that a subpopulation of multiple sclerosis patients shows evidence of
      hypothalamic-pituitary-adrenocortical axis desensitization.

PMID- 11459811
TI  - Experimental cardiac fibrosis: differential time course of responses to
      mineralocorticoid-salt administration.
AB  - The rapid (1-4 h) responses of epithelial target tissues to mineralocorticoids
      contrast with the days/weeks apparently required for responses in the
      cardiovascular system. The present study explores the time course and pattern of
      early events leading to cardiac fibrosis in the mineralocorticoid-salt rat model.
      Uninephrectomized rats were given deoxycorticosterone (20 mg, sc, weekly) plus
      0.9% NaCl/0.3% KCl to drink and were killed at 2, 4, 8, 16, and 32 d. Type III
      collagen increased progressively from d 2, and blood pressure from d 4, with 4
      and 8 d rats showing marked perivascular inflammatory cell infiltration.
      Apoptosis was also noted in perivascular areas at 4 and 8 d and in scar areas at
      8, 16, and 32 d. Elevation of mineralocorticoid hormone levels inappropriate for
      salt status thus provokes a series of changes in cardiac vessels and myocytes
      leading to increased collagen deposition. When mineralocorticoid levels are
      elevated acutely by bolus injection, changes are discernible after 2 d, in
      contrast with previous infusion studies in which 3-4 wk were required for
      measurable changes.

PMID- 11459812
TI  - Reciprocal control of expression of mRNAs for osteoclast differentiation factor
      and OPG in osteogenic stromal cells by genistein: evidence for the involvement of
      topoisomerase II in osteoclastogenesis.
AB  - Osteoclast-like cells, in cocultures with mouse spleen cells and clonal
      osteogenic stromal ST2 cells, are formed from spleen cells with
      monocyte/macrophage lineage in response to a combination of osteoclast
      differentiation factor (RANKL) and OPG, a decoy receptor for RANKL, produced by
      ST2 cells in response to 1alpha,25-dihydroxyvitamin D(3). Treatment of ST2 cells
      with the natural isoflavonoid genistein for 6 h before coculture with spleen
      cells inhibited the formation of tartrate-resistant acid phosphatase-positive
      osteoclast-like cells. When we measured levels of RANKL mRNA in ST2 cells, we
      found that genistein decreased the level of this mRNA. By contrast, the level of
      OPG mRNA was enhanced by genistein. Genistein is a specific inhibitor of
      topoisomerase II (topo II) and an inhibitor of protein tyrosine kinase, as well
      as being a potent phytoestrogen. To characterize the mode of action of genistein,
      we examined the effects of an inactive form of genistein (daidzein), 17beta
      estradiol, inhibitors of topo II, and inhibitors of tyrosine kinases on the
      formation of tartrate-resistant acid phosphatase-positive osteoclast-like cells.
      Among the compounds tested, two inhibitors of topo II, amsacrine and etoposide,
      attenuated the formation of osteoclast-like cells via reciprocal regulation of
      the expression of mRNAs for RANKL and OPG in ST2 cells, acting similarly to
      genistein. Our findings indicate that genistein might inhibit the formation of
      osteoclast-like cells via inhibition of the activity of topo II, suggesting the
      novel possibility that topo II might play an important role in
      osteoclastogenesis.

PMID- 11459813
TI  - Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell
      fusion and differentiation.
AB  - The syncytiotrophoblast is the major component of the human placenta, involved in
      feto-maternal exchanges and secretion of pregnancy-specific hormones.
      Multinucleated syncytiotrophoblast arises from fusion of mononuclear
      cytotrophoblast cells. In trisomy 21-affected placentas, we recently have shown
      that there is a defect in syncytiotrophoblast formation and a decrease in the
      production of pregnancy-specific hormones. Due to the role of oxygen free
      radicals in trophoblast cell differentiation, we investigated the role of the key
      antioxidant enzyme, copper/zinc superoxide dismutase, encoded by chromosome 21 in
      in vitro trophoblast differentiation. We first observed that overexpression of
      superoxide dismutase in normal cytotrophoblasts impaired syncytiotrophoblast
      formation. This was associated with a significant decrease in mRNA transcript
      levels and secretion of hCG and other hormonal markers of syncytiotrophoblast. We
      confirmed abnormal cell fusion by overexpression of green fluorescence protein
      tagged superoxide dismutase in cytotrophoblasts. In addition, a significant
      decrease in syncytin transcript levels was observed in superoxide dismutase
      transfected cells. We then examined superoxide dismutase expression and activity
      in isolated trophoblast cells from trisomy 21-affected placentas. Superoxide
      dismutase mRNA expression (P < 0.05), protein levels (P < 0.01), and activity (P
      < 0.05) were significantly higher in trophoblast cells isolated from trisomy 21
      affected placentas than in those from normal placentas. These results suggest
      that superoxide dismutase overexpression may directly impair trophoblast cell
      differentiation and fusion, and superoxide dismutase overexpression in Down's
      syndrome may be responsible at least in part for the failure of
      syncytiotrophoblast formation observed in trisomy 21-affected placentas.

PMID- 11459814
TI  - Expression of calbindin-D(28k) in a pancreatic islet beta-cell line protects
      against cytokine-induced apoptosis and necrosis.
AB  - Cytokines produced by immune system cells that infiltrate pancreatic islets are
      candidate mediators of islet beta-cell destruction in autoimmune (type 1)
      diabetes mellitus. Because the calcium binding protein, calbindin-D(28k), can
      prevent apoptotic cell death in different cell types, we investigated the
      possibility that calbindin-D(28k) may prevent cytokine-mediated islet beta-cell
      destruction. Using the expression vector BSRalpha, rat calbindin-D(28k) was
      stably expressed in the pancreatic islet beta-cell line, betaTC-3. Calbindin
      D(28k) expression resulted in increased cell survival in the presence of the
      cytotoxic combination of the cytokines IL-1beta (30 U/ml), TNFalpha (10(3) U/ml),
      and interferon gamma (10(3) U/ml). The greatest protection was observed in the
      betaTC-3 cell clone expressing the highest concentration of calbindin-D(28k).
      Apoptotic cell death was detected by annexin V staining and by the TdT-mediated
      dUTP-X nick end labeling assay in vector-transfected betaTC-3 cells incubated
      with cytokines (14-15% apoptotic cells). The number of apoptotic cells was
      significantly decreased in calbindin-D(28k)-overexpressing betaTC-3 cells
      incubated with cytokines (5-6% apoptotic cells). To address the mechanism of the
      antiapoptotic effects of calbindin, studies were done to examine whether
      calbindin inhibits free radical formation. The stimulatory effects of the
      cytokines on lipid hydroperoxide, nitric oxide, and peroxynitrite production were
      significantly decreased in the calbindin-D(28k)-expressing betaTC-3 cells. Our
      findings indicate that calbindin-D(28k), by inhibiting free radical formation,
      can protect against cytokine-mediated apoptosis and destruction of beta-cells.
      These findings suggest that calbindin-D(28k) may be an important regulator of
      cell death that can protect pancreatic islet beta-cells from autoimmune
      destruction in type 1 diabetes.

PMID- 11459815
TI  - Bone morphogenetic protein 2 stimulates osteoclast differentiation and survival
      supported by receptor activator of nuclear factor-kappaB ligand.
AB  - Bone is a major storage site for TGFbeta superfamily members, including TGFbeta
      and bone morphogenetic proteins. It is believed that these cytokines are released
      from bone during bone resorption. Recent studies have shown that both RANKL and
      macrophage colony-stimulating factor are two essential factors produced by
      osteoblasts for inducing osteoclast differentiation. In the present study we
      examined the effects of bone morphogenetic protein-2 on osteoclast
      differentiation and survival supported by RANKL and/or macrophage colony
      stimulating factor. Mouse bone marrow-derived macrophages differentiated into
      osteoclasts in the presence of RANKL and macrophage colony-stimulating factor.
      TGFbeta superfamily members such as bone morphogenetic protein-2, TGFbeta, and
      activin A markedly enhanced osteoclast differentiation induced by RANKL and
      macrophage colony-stimulating factor, although each cytokine alone failed to
      induce osteoclast differentiation in the absence of RANKL. Addition of a soluble
      form of bone morphogenetic protein receptor type IA to the culture markedly
      inhibited not only osteoclast formation induced by RANKL and bone morphogenetic
      protein-2, but also the basal osteoclast formation supported by RANKL alone.
      Either RANKL or macrophage colony-stimulating factor stimulated the survival of
      purified osteoclasts. Bone morphogenetic protein-2 enhanced the survival of
      purified osteoclasts supported by RANKL, but not by macrophage colony-stimulating
      factor. Both bone marrow macrophages and mature osteoclasts expressed bone
      morphogenetic protein-2 and bone morphogenetic protein receptor type IA mRNAs. An
      EMSA revealed that RANKL activated nuclear factor-kappaB in purified osteoclasts.
      Bone morphogenetic protein-2 alone did not activate nuclear factor-kappaB, but
      rather inhibited the activation of nuclear factor-kappaB induced by RANKL in
      purified osteoclasts. These findings suggest that bone morphogenetic protein
      mediated signals cross-communicate with RANKL-mediated ones in inducing
      osteoclast differentiation and survival. The enhancement of RANKL-induced
      survival of osteoclasts by bone morphogenetic protein-2 appears unrelated to
      nuclear factor-kappaB activation.

PMID- 11459816
TI  - Gastrin induces expression and promoter activity of the vesicular monoamine
      transporter subtype 2.
AB  - Gastric enterochromaffin-like cells produce histamine in response to the antral
      hormone gastrin and accumulate the biogenic amine in secretory organelles via
      vesicular monoamine transporter subtype 2. The putative effects of gastrin on
      vesicular monoamine transporter subtype 2 expression and promoter activity are
      poorly understood. In the present study we used highly enriched rat
      enterochromaffin-like cells (purity, >90%) and rat pheochromocytoma cells stably
      transfected with a gastrin/cholecystokinin B receptor to investigate the
      expression and transcriptional regulation of vesicular monoamine transporter
      subtype 2. Stimulation of vesicular monoamine transporter subtype 2 mRNA and
      protein expression was observed in isolated enterochromaffin-like cells after 3-
      to 7-h incubation with gastrin (10(-7) M), forskolin (10(-5) M), or ionomycin
      (10(-5) M). Deletion analysis of the rat vesicular monoamine transporter subtype
      2 promoter defined the minimal promoter sequence necessary for full basal
      activity as a -121 bp segment upstream of exon 1 containing two Sp1 sites (-97 to
      -88 bp and -68 to -59 bp) and a cAMP-responsive element (-44 to -35 bp). Gastrin
      (10(-7) M) stimulated extracellular signal related kinase1/2 phosphorylation,
      activated Sp1 and cAMP-responsive element-binding protein, and further induced
      activity of the complete rat vesicular monoamine transporter subtype 2 promoter (
      800 bp) in gastrin/cholecystokinin B receptor cells. The -121-bp fragment was
      able to confer full gastrin responsiveness, and site-directed mutagenesis of the
      Sp1 and cAMP-responsive element motifs demonstrated their crucial importance for
      basal and inducible activities. Comparison of promoter activity of histidine
      decarboxylase, chromogranin A, or vesicular monoamine transporter subtype 2 in
      transfected cell lines revealed significant differences in basal and gastrin
      stimulated activities. Our current study provides the first evidence that gastrin
      directly stimulates the expression and promoter activity of vesicular monoamine
      transporter subtype 2. Sp1 and cAMP-responsive element-binding protein
      recognition motifs located within 121 bp upstream of exon 1 appear to be
      indispensable for full basal and inducible promoter activities. Diverging effects
      of gastrin on histidine decarboxylase, chromogranin A, and vesicular monoamine
      transporter subtype 2 promoter may account for the coordinated synthesis and
      storage of histamine in this neuroendocrine cell type.

PMID- 11459817
TI  - Ovarian pathology and high incidence of sex cord tumors in follitropin receptor
      knockout (FORKO) mice.
AB  - In this investigation we describe our observations of the status of the aging
      ovary in mice with disruption of the receptor for FSH. Knockout mice at 3-5
      months of age are acyclic and sterile, with very small, underdeveloped ovaries.
      Thus, they exhibit hypergonadotropic-hypogonadism with high levels of circulating
      FSH similar to the postmenopausal state in women. By 12 months more than 92% of
      these animals developed various kinds of ovarian pathology, including neoplasms
      of sex cord-stromal type as well as cysts. Interestingly, the majority of tumors
      were located in the right ovary, with the contralateral ovary remaining
      unaffected but atrophic. The ovary from heterozygotes also showed pathology after
      15 months. None of the age-matched wild-type mice that remained fertile developed
      any sign of ovarian tumors. Circulating LH and FSH levels were increased in
      follitropin receptor knockout mice and remained severalfold higher in tumor
      bearing animals. The histological appearances of ovarian tumors were similar to
      the pathology observed in some types of sex cord-stromal neoplasms in women. The
      tumor burden caused weight loss and cachexia in follitropin receptor knockout
      mice. Based on these characteristics as well as the high incidence of ovarian
      pathology in the aging mutant, we propose that the loss of the FSH receptor
      signaling mechanisms predispose the ovary to molecular and structural changes
      leading to tumor formation. Hence, in the intact and fertile animal, FSH receptor
      signaling offers a protective mechanism that is lost upon reproductive senescence
      (menopause in women). Further studies are warranted in this genetic model to
      explore the molecular changes underlying the development of ovarian neoplasia.

PMID- 11459818
TI  - Expression of the mRNAs and Proteins for the Na(+)/H(+) exchangers and their
      regulatory factors in baboon and human placental syncytiotrophoblast.
AB  - In polarized epithelial cells of several organ systems, e.g. the kidney, a family
      of Na(+)/H(+) exchangers (e.g. Na(+)/H(+) exchanger-1 and -3) and their
      regulatory proteins, Na(+)/H(+) exchanger regulatory factor and Na(+)/H(+)
      exchanger-3 kinase A regulatory protein play a major role in regulating
      Na(+)/H(+) exchange integral to cellular homeostasis. Because the primate
      placenta regulates exchange of Na(+) and H(+) between the mother and fetus
      critical to fetal-placental homeostasis, the current study determined whether
      Na(+)/H(+) exchanger-1 and -3 were compartmentalized and associated with
      expression of Na(+)/H(+) exchanger regulatory factor and Na(+)/H(+) exchanger-3
      kinase A regulatory protein in baboon and human syncytiotrophoblast. Using RT
      PCR, single 413-bp Na(+)/H(+) exchanger-1 and 190-bp Na(+)/H(+) exchanger-3
      products were expressed by baboon and human syncytiotrophoblasts. The 104-kDa
      Na(+)/H(+) exchanger-1 protein was detected by Western blot in microvillus
      membranes and to a much lesser extent in the basal membranes of the baboon and
      human syncytiotrophoblasts. In contrast, the 85-kDa Na(+)/H(+) exchanger-3
      protein was detected primarily in membranes contiguous with the basal membranes
      of the syncytiotrophoblast of both species. Differential localization of
      Na(+)/H(+) exchanger-1 and -3 was confirmed by immunocytochemistry. The
      Na(+)/H(+) exchanger-3 regulatory protein, Na(+)/H(+) exchanger-3 kinase A
      regulatory protein, resided almost exclusively in the basal membranes, whereas
      Na(+)/H(+) exchanger regulatory factor was localized primarily to the microvillus
      membranes in the baboon and human syncytiotrophoblast. Collectively, these
      results are the first to show that the baboon and human term placental
      syncytiotrophoblast expressed the mRNAs and proteins for Na(+)/H(+) exchanger-1
      and -3 and their regulatory factors and that Na(+)/H(+) exchanger-1 and
      Na(+)/H(+) exchanger regulatory factor resided primarily in the microvillus
      membranes, whereas Na(+)/H(+) exchanger-3 and Na(+)/H(+) exchanger-3 kinase A
      regulatory protein were localized to membranes contiguous with the basal
      membranes and to the basal membranes, respectively. We conclude that a complete
      Na(+)/H(+) exchange system is present in the baboon and human term placental
      syncytiotrophoblast and suggest that the primate placenta exhibits polarity with
      respect to the capacity for regulation of Na(+)/H(+) exchange between the
      placenta and the maternal and fetal circulations.

PMID- 11459819
TI  - Stimulation effect of galanin-like peptide (GALP) on luteinizing hormone
      releasing hormone-mediated luteinizing hormone (LH) secretion in male rats.
AB  - Galanin-like peptide (GALP) is a recently isolated hypothalamic peptide which has
      sequence homology to galanin and binds to galanin receptors with high affinity.
      It has been shown that GALP neurons are localized in the arcuate nucleus and that
      GALP-immunoreactive fibers are in close apposition with LHRH neurons in the
      medial preoptic area (MPA). In the present study, we found that
      intracerebroventricular (icv) administration of GALP increased the plasma LH
      level but did not change the levels of other hormones. Concomitantly,
      accumulation of c-Fos protein was dramatically increased in the nuclei of LHRH
      positive cells in the MPA by icv GALP administration. Furthermore, the GALP
      induced plasma LH response was completely abolished by pretreatment with
      Cetrorelix, a LHRH receptor antagonist. On the other hand, GALP did not affect
      the release of LH, FSH, TSH, ACTH, GH or PRL directly from dispersed rat
      pituitary cells in vitro. These results strongly suggest a role for GALP in the
      control of gonadotropin secretion through a hypothalamic mechanism involving the
      release of LHRH.

PMID- 11459820
TI  - Organization of the mouse ghrelin gene and promoter: occurrence of a short
      noncoding first exon.
AB  - Ghrelin is a growth hormone-releasing peptide recently discovered in the stomach
      of rat and human as an endogenous ligand for growth hormone-secretagogue
      receptor. In the present study, a full-length cDNA for mouse ghrelin has been
      cloned from the stomach using the oligo-capping and rapid amplification methods,
      and the organization of its gene and promoter has been analyzed. The mouse
      ghrelin cDNA was 521 bp long, consisting of 44 bp 5'-noncoding region, 354 bp
      coding region encoding a pre-proghrelin composed of 117 amino acid residues and
      123 bp 3'-noncoding region. The genomic sequence analysis has revealed that the
      mouse ghrelin gene consists of 5 exons and 4 introns. The first exon was revealed
      to be only 19 bp long presented at the noncoding region of cDNA. The identical 19
      bp sequence was also found as the first exon at the 5'-end of full-length rat
      ghrelin cDNA obtained from the stomach. A TATA box-like sequence, TATATAA was
      localized 24 bp upstream of the transcription start site of the mouse ghrelin
      gene. The sequence of the 5'-promoter region of mouse ghrelin gene including the
      TATA-like sequence and short exon 1 was highly homologous to that of reported
      human ghrelin gene. These findings suggest that the structure of the promoter
      region including the short noncoding first exon and its transcriptional
      regulation are conserved among the mammalian ghrelin genes.

PMID- 11459823
TI  - Protein secretion and the pathogenesis of bacterial infections.

PMID- 11459824
TI  - Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing
      of an endogenous gene.
AB  - Plants maintain cytosine methylation at CG and non-CG residues to control gene
      expression and genome stability. In a screen for Arabidopsis mutants that alter
      methylation and silencing of a densely methylated endogenous reporter gene, we
      recovered 11 loss-of-function alleles in the CMT3 chromomethylase gene. The cmt3
      mutants displayed enhanced expression and reduced methylation of the reporter,
      particularly at non-CG cytosines. CNG methylation was also reduced at repetitive
      centromeric sequences. Thus, CMT3 is a key determinant for non-CG methylation.
      The lack of CMT homologs in animal genomes could account for the observation that
      in contrast to plants, animals maintain primarily CG methylation.

PMID- 11459825
TI  - Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for
      regulating Cdh1.
AB  - Exit from mitosis requires the degradation of regulatory proteins including the
      mitotic cyclins and securin through ubiquitination by the anaphase promoting
      complex (APC) bound to Cdc20 or Cdh1. Cdc20-APC is regulated through inhibition
      by the spindle assembly checkpoint protein MAD2. Knowledge of Cdh1-APC regulation
      is limited to the phosphorylation-dependent dissociation of Cdh1 from APC. We
      report a novel means of regulating Cdh1 by the MAD2-related gene, MAD2L2. MAD2L2
      specifically binds and inhibits Cdh1-APC, paralleling the effect of MAD2 on
      Cdc20. We suggest that MAD2L2 and MAD2 inhibit the release of substrates from APC
      and propose a mechanism of inhibition.

PMID- 11459826
TI  - MAD2B is an inhibitor of the anaphase-promoting complex.
AB  - Anaphase-promoting complex (APC), a ubiquitin ligase, controls both sister
      chromatid separation and mitotic exit. The APC is activated in mitosis and G1 by
      CDC20 and CDH1, and inhibited by the checkpoint protein MAD2, a specific
      inhibitor of CDC20. We show here that a MAD2 homolog MAD2B also inhibits APC. In
      contrast to MAD2, MAD2B inhibits both CDH1-APC and CDC20-APC. This inhibition is
      targeted to CDH1 and CDC20, but not directly to APC. Unlike MAD2, whose
      interaction with MAD1 is required for mitotic checkpoint control, MAD2B does not
      interact with MAD1, suggesting that MAD2B may relay a different cellular signal
      to APC.

PMID- 11459827
TI  - Messenger RNAs are recruited for nuclear export during transcription.
AB  - Following transcription and processing, eukaryotic mRNAs are exported from the
      nucleus to the cytoplasm for translation. Here we present evidence that mRNAs are
      targeted for nuclear export cotranscriptionally. Combined mutations in the
      Saccharomyces cerevisiae hnRNP Npl3 and TATA-binding protein (TBP) block mRNA
      export, implying that cotranscriptional recruitment of Npl3 is required for
      efficient export of mRNA. Furthermore, Npl3 can be found in a complex with RNA
      Pol II, indicating that Npl3 associates with the transcription machinery.
      Finally, Npl3 is recruited to genes in a transcription dependent manner as
      determined by chromatin immunoprecipitation. Another mRNA export factor, Yra1,
      also associates with chromatin cotranscriptionally but appears to be recruited at
      a later step. Taken together, our results suggest that export factors are
      recruited to the sites of transcription to promote efficient mRNA export.

PMID- 11459828
TI  - Capping, splicing, and 3' processing are independently stimulated by RNA
      polymerase II: different functions for different segments of the CTD.
AB  - Capping, splicing, and cleavage/polyadenylation of pre-mRNAs are interdependent
      events that are all stimulated in vivo by the carboxy-terminal domain (CTD) of
      RNA Pol II. We show that the CTD independently enhances splicing and 3'
      processing and that stimulation of splicing by enhancers is facilitated by the
      CTD. We provide evidence that stimulation of 3' processing by the CTD requires
      contact with the 50-kD subunit of the cleavage stimulation factor, CstF.
      Overexpression of the CTD-binding domain of CstF p50 had a dominant-negative
      effect on 3' processing without disrupting the CstF complex. The CTD comprises 52
      heptad repeats. The CTD carboxyl terminus including heptads 27-52 supported
      capping, splicing, and 3' processing but the amino terminus supported only
      capping. We conclude that the CTD independently stimulates all three major pre
      mRNA processing steps and that different regions of the CTD can serve distinct
      functions in pre-mRNA processing.

PMID- 11459829
TI  - Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1.
AB  - We report the isolation and cloning of the Wrch-1 (Wnt-1 responsive Cdc42
      homolog) cDNA. Wrch-1 is a novel gene whose mRNA level increases in response to
      Wnt-1 signaling in Wnt-1 transformed cells, Wnt-1 transgene induced mouse mammary
      tumors, and Wnt-1 retrovirus infected cells. Wrch-1 encodes a homolog of the Rho
      family of GTPases. It shares 57% amino acid sequence identity with Cdc42, but
      possesses a unique N-terminal domain that contains several putative PXXP SH3
      binding motifs. Like Cdc42, Wrch-1 can activate PAK-1 and JNK-1, and induce
      filopodium formation and stress fiber dissolution. Active Wrch-1 stimulates
      quiescent cells to reenter the cell cycle. Moreover, overexpression of Wrch-1
      phenocopies Wnt-1 in morphological transformation of mouse mammary epithelial
      cells. Taken together, Wrch-1 could mediate the effects of Wnt-1 signaling in the
      regulation of cell morphology, cytoskeletal organization, and cell proliferation.

PMID- 11459830
TI  - Inactivation of AtRac1 by abscisic acid is essential for stomatal closure.
AB  - Plant water homeostasis is maintained by the phytohormone abscisic acid (ABA),
      which triggers stomatal pore closure in response to drought stress. We identified
      the Arabidopsis small guanosine triphosphatase (GTPase) protein AtRac1 as a
      central component in the ABA-mediated stomatal closure process. ABA treatment
      induced inactivation of AtRac GTPases and disruption of the guard cell actin
      cytoskeleton. In contrast, in the ABA-insensitive mutant abi1-1, which is
      impaired in stomatal closure, neither AtRac inactivation nor actin cytoskeleton
      disruption was observed on ABA treatment. These observations indicate that AtRac1
      inactivation is a limiting step in the ABA-signaling cascade leading to stomatal
      closure. Consistent with these findings, expression of a dominant-positive mutant
      of AtRac1 blocked the ABA-mediated effects on actin cytoskeleton and stomatal
      closure in wild-type plants, whereas expression of a dominant-negative AtRac1
      mutant recapitulated the ABA effects in the absence of the hormone. Moreover, the
      dominant-negative form of AtRac1 could also restore stomatal closure in abi1-1.
      These results define AtRac1 as a central element for plant adaptation to drought.

PMID- 11459831
TI  - Down-regulation of TDT transcription in CD4(+)CD8(+) thymocytes by Ikaros
      proteins in direct competition with an Ets activator.
AB  - Ikaros is a unique regulator of lymphopoiesis that associates with
      pericentromeric heterochromatin and has been implicated in heritable gene
      inactivation. Binding and competition experiments demonstrate that Ikaros dimers
      compete with an Ets activator for occupancy of the lymphocyte-specific TdT
      promoter. Mutations that selectively disrupt Ikaros binding to an integrated TdT
      promoter had no effect on promoter function in a CD4(+)CD8(+) thymocyte line.
      However, these mutations abolished down-regulation on differentiation, providing
      evidence that Ikaros plays a direct role in repression. Reduced access to
      restriction enzyme cleavage suggested that chromatin alterations accompany down
      regulation. The Ikaros-dependent down-regulation event and the observed chromatin
      alterations appear to precede pericentromeric repositioning. Current models
      propose that the functions of Ikaros should be disrupted by a small isoform that
      retains the dimerization domain and lacks the DNA-binding domain. Surprisingly,
      in the CD4(+)CD8(+) thymocyte line, overexpression of a small Ikaros isoform had
      no effect on differentiation or on the pericentromeric targeting and DNA-binding
      properties of Ikaros. Rather, the small isoform assembled into multimeric
      complexes with DNA-bound Ikaros at the pericentromeric foci. The capacity for in
      vivo multimer formation suggests that interactions between Ikaros dimers bound to
      the TdT promoter and those bound to pericentromeric repeat sequences may
      contribute to the pericentromeric repositioning of the inactive gene.

PMID- 11459832
TI  - Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent
      phosphorylation.
AB  - Previous work has established a role for p53 in triggering apoptosis in response
      to DNA damage; p53 also induces apoptosis in response to deregulation of the Rb
      cell cycle pathway. The latter event is consistent with a role for the Rb
      regulated E2F1 protein as a specific inducer of apoptosis and p53 accumulation.
      We now show that DNA damage leads to a specific induction of E2F1 accumulation,
      dependent on ATM kinase activity and that the specificity of E2F1 induction
      reflects a specificity in the phosphorylation of E2F1 by ATM as well as the
      related kinase ATR. We identify a site for ATM/ATR phosphorylation in the amino
      terminus of E2F1 and we show that this site is required for ATM-mediated
      stabilization of E2F1. Finally, we also show that E2F1 is required for DNA
      damaged induced apoptosis in mouse thymocytes. We conclude that the cellular
      response to DNA damage makes use of signals from the Rb/E2F cell cycle pathway.

PMID- 11459833
TI  - The set1Delta mutation unveils a novel signaling pathway relayed by the Rad53
      dependent hyperphosphorylation of replication protein A that leads to
      transcriptional activation of repair genes.
AB  - SET domain proteins are present in chromosomal proteins involved in epigenetic
      control of transcription. The yeast SET domain protein Set1p regulates chromatin
      structure, DNA repair, and telomeric functions. We investigated the mechanism by
      which the absence of Set1p increases DNA repair capacities of checkpoint mutants.
      We show that deletion of SET1 induces a response relayed by the signaling kinase
      Rad53p that leads to the MEC1/TEL1-independent hyperphosphorylation of
      replication protein A middle subunit (Rfa2p). Consequently, the binding of Rfa2p
      to upstream repressing sequences (URS) of repair genes is decreased, thereby
      leading to their derepression. Our results correlate the set1Delta-dependent
      phosphorylation of Rfa2p with the transcriptional induction of repair genes.
      Moreover, we show that the deletion of the amino-terminal region of Rfa2p
      suppresses the sensitivity to ultraviolet radiation of a mec3Delta checkpoint
      mutant, abolishes the URS-mediated repression, and increases the expression of
      repair genes. This work provides an additional link for the role of Rfa2p in the
      regulation of the repair capacity of the cell and reveals a role for the
      phosphorylation of Rfa2p and unveils unsuspected connections between chromatin,
      signaling pathways, telomeres, and DNA repair.

PMID- 11459834
TI  - SWITCH1 (SWI1): a novel protein required for the establishment of sister
      chromatid cohesion and for bivalent formation at meiosis.
AB  - We have characterized a new gene, SWI1, involved in sister chromatid cohesion
      during both male and female meiosis in Arabidopsis thaliana. A first allele,
      swi1.1, was obtained as a T-DNA tagged mutant and was described previously as
      abnormal exclusively in female meiosis. We have isolated a new allele, swi1.2,
      which is defective for both male and female meiosis. In swi1.2 male meiosis, the
      classical steps of prophase were not observed, especially because homologs do not
      synapse. Chromatid arms and centromeres lost their cohesion in a stepwise manner
      before metaphase I, and 20 chromatids instead of five bivalents were seen at the
      metaphase plate, which was followed by an aberrant segregation. In contrast,
      swi1.2 female meiocytes performed a mitotic-like division instead of meiosis,
      indicating a distinct role for SWI1 or a different effect of the loss of SWI1
      function in both processes. The SWI1 gene was cloned; the putative SWI1 protein
      did not show strong similarity to any known protein. Plants transformed with a
      SWI1-GFP fusion indicated that SWI1 protein is present in meiocyte nuclei, before
      meiosis and at a very early stage of prophase. Thus, SWI1 appears to be a novel
      protein involved in chromatid cohesion establishment and in chromosome structure
      during meiosis, but with clear differences between male and female meiosis.

PMID- 11459835
TI  - A mitogenic signal triggered at an early stage of vaccinia virus infection:
      implication of MEK/ERK and protein kinase A in virus multiplication.
AB  - Vaccinia virus (VV) triggers a mitogenic signal at an early stage of infection.
      VV-induced proto-oncogene c-fos mRNA with kinetics paralleling that stimulated by
      serum. The VV virokine, or vaccinia virus growth factor (VGF), was not crucial
      for c-fos induction because it was observed upon infection with the virokine
      minus mutant VV (VGF(-)). Furthermore, c-fos expression did not require
      infectious virus particles, as it occurred even with UV-inactivated VV and was
      equally induced by the different multiplicities of infection, i.e. 1.0, 5.0, and
      25.0. c-fos expression was preceded by VV-induced DNA binding activity and was
      mediated via the cis-acting elements serum response element (SRE), activating
      protein-1 (AP-1), and cAMP-response element (CRE). VV activated the protein
      kinases p42MAPK/ERK2 and p44MAPK/ERK1 and the transcription factor ATF1 in a time
      dependent manner with kinetics that paralleled those of VV-stimulated DNA-protein
      complex formation. The mitogenic signal transmission pathways leading to c-fos
      activation upon VV infection were apparently mediated by the protein kinases MEK,
      ERK, and PKA. This assumption was based on the findings that: 1) c-fos transcript
      was down-regulated; 2) the SRE, AP-1, and CRE binding activities were
      significantly reduced; and 3) the activation of p42MAPK/ERK2, p44MAPK/ERK1, and
      ATF1 were drastically affected when the viral infections were carried out in the
      presence of specific protein kinase inhibitor. Moreover, the mutant VV (VGF(-))
      was also able to activate ERK1/2. It is noteworthy that virus multiplication was
      equally affected by the same kinase inhibitors. Taken together, our data provide
      evidence that the early mitogenic signal triggered upon VV infection relies upon
      the activation of the protein kinases MEK, ERK, and PKA, which are needed for
      both signal transduction and virus multiplication.

PMID- 11459836
TI  - BphS, a key transcriptional regulator of bph genes involved in polychlorinated
      biphenyl/biphenyl degradation in Pseudomonas sp. KKS102.
AB  - The bph genes in Pseudomonas sp. KKS102, which are involved in the degradation of
      polychlorinated biphenyl/biphenyl, are induced in the presence of biphenyl. In
      this study our goal was to understand the regulatory mechanisms involved in the
      inducible expression. The bph genes (bphEGF(orf4)A1A2A3BCD(orf1)A4R) constitute
      an operon, and its expression is strongly dependent on the pE promoter located
      upstream of the bphE gene. A bphS gene, whose deduced amino acid sequence showed
      homology with the GntR family transcriptional repressors, was identified at the
      upstream region of the bphE gene. Disruption of the bphS gene resulted in
      constitutive expression of bph genes, suggesting that the bphS gene product
      negatively regulated the pE promoter. The gel retardation and DNase footprinting
      analyses demonstrated specific binding of BphS to the pE promoter region and
      identified four BphS binding sites that were located within and immediately
      downstream of the -10 box of the pE promoter. The four binding sites were
      functional in repression because their respective elimination resulted in
      derepression of the pE promoter. The binding of BphS was abolished in the
      presence of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid, an intermediate
      compound in the biphenyl degradation pathway. We concluded that the negative
      regulator BphS plays a central role in the regulation of bph gene expression
      through its action at the pE promoter.

PMID- 11459837
TI  - The interaction of bovine adrenodoxin with CYP11A1 (cytochrome P450scc) and
      CYP11B1 (cytochrome P45011beta ). Acceleration of reduction and substrate
      conversion by site-directed mutagenesis of adrenodoxin.
AB  - The kinetics of protein-protein interaction and heme reduction between
      adrenodoxin wild type as well as eight mutants and the cytochromes P450 CYP11A1
      and CYP11B1 was studied in detail. Rate constants for the formation of the
      reduced CYP11A1.CO and CYP11B1.CO complexes by wild type adrenodoxin, the
      adrenodoxin mutants Adx-(4-108), Adx-(4-114), T54S, T54A, and S112W, and the
      double mutants Y82F/S112W, Y82L/S112W, and Y82S/S112W (the last four mutants are
      Delta113-128) are presented. The rate constants observed differ by a factor of up
      to 10 among the respective adrenodoxin mutants for CYP11A1 but not for CYP11B1.
      According to their apparent rate constants for CYP11A1, the adrenodoxin mutants
      can be grouped into a slow (wild type, T54A, and T54S) and a fast group (all the
      other mutants). The adrenodoxin mutants forming the most stable complexes with
      CYP11A1 show the fastest rates of reduction and the highest rate constants for
      cholesterol to pregnenolone conversion. This strong correlation suggests that C
      terminal truncation of adrenodoxin in combination with the introduction of a C
      terminal tryptophan residue enables a modified protein-protein interaction
      rendering the system almost as effective as the bacterial putidaredoxin/CYP101
      system. Such a variation of the adrenodoxin structure resulted in a mutant
      protein (S112W) showing a 100-fold increased efficiency in conversion of
      cholesterol to pregnenolone.

PMID- 11459838
TI  - Identification and pharmacological characterization of a novel human melanin
      concentrating hormone receptor, mch-r2.
AB  - Melanin-concentrating hormone (MCH) is a neuropeptide highly expressed in the
      brain that regulates several physiological functions mediated by receptors in the
      G protein-coupled receptor family. Recently an orphan receptor, SLC-1, has been
      identified as an MCH receptor (MCH-R1). Herein we identify and characterize a
      novel receptor for human MCH (MCH-R2). The receptor is composed of 340 amino
      acids encoded by a 1023-base pair cDNA and is 35% homologous to SLC-1. (125)I-MCH
      specifically bound to Chinese hamster ovary cells stably expressing MCH-R2. MCH
      stimulated dose-dependent increases in intracellular free Ca(2+) and inositol
      phosphate production in these cells but did not affect cAMP production. The
      pharmacological profile for mammalian MCH, [Phe(13),Tyr(19)]MCH, and salmon MCH
      at MCH-R2 differed compared with MCH-R1 as assessed by intracellular signaling
      and radioligand binding assays. The EC(50) in signaling assays and the IC(50) in
      radioligand binding assays of salmon MCH was an order of magnitude higher than
      mammalian MCH at MCH-R2. By comparison, the EC(50) and IC(50) values of salmon
      MCH and mammalian MCH at MCH-R1 were relatively similar. Blot hybridization
      revealed exclusive expression of MCH-R2 mRNA in several distinct brain regions,
      particularly in the cortical area, suggesting the involvement of MCH-R2 in the
      central regulation of MCH-mediated functions.

PMID- 11459839
TI  - In vitro reconstitution of insertion and processing of cytochrome f in a
      homologous chloroplast translation system.
AB  - Using a homologous chloroplast translation system, we have reconstituted
      insertion and processing of the chloroplast-encoded thylakoid protein cytochrome
      f (pCytf). Cross-linking demonstrated that pCytf nascent chains when attached to
      the 70 S ribosome tightly interact with cpSecA, but this is strictly dependent on
      thylakoid membranes and a functional signal peptide. This indicates that cpSecA
      is only operative in pCytf biogenesis when it is bound to the membrane, most
      likely as part of the Sec translocon. No evidence for interaction between the 54
      kDa subunit of the chloroplast signal recognition particle (cpSRP) and the pCytf
      nascent chain could be detected, suggesting that pCytf, in contrast to the
      polytopic D1 protein, does not require cpSRP for targeting. Insertion of pCytf
      occurred only co-translationally, resulting in processing and accumulation of
      both the processed signal peptide and the mature protein in the thylakoid. This
      co-translational membrane insertion and processing required a functional signal
      peptide and was inhibited by azide, demonstrating that cpSecA is essential for
      translocation of the soluble luminal domain. pCytf also associated post
      translationally with thylakoids, but the soluble N-terminal domain could not be
      translocated into the lumen. This is the first study in which synthesis,
      targeting, and insertion of a chloroplast-encoded thylakoid membrane protein is
      reconstituted from exogenous transcripts and using the chloroplast translational
      machinery.

PMID- 11459840
TI  - The role of tyrosine residues in fibroblast growth factor receptor 1 signaling in
      PC12 cells. Systematic site-directed mutagenesis in the endodomain.
AB  - To assess the contribution of the intracellular domain tyrosine residues to the
      signaling capacity of fibroblast growth factor receptor 1 (FGFR1), stably
      transfected chimeras bearing the ectodomain of the platelet-derived growth factor
      receptor (PDGFR) and the endodomain of FGFR1 were systematically altered by a
      tyrosine to phenylalanine bloc and individual conversions. The 15 tyrosine
      residues of the endodomain of this construct (PFR1) were divided into four linear
      segments (labeled A, B, C, and D) that contained 4, 4, 2, and 5 tyrosine
      residues, respectively. When stimulated by platelet-derived growth factor,
      derivatives in which the A, B, or A + B blocs of tyrosines were mutated were
      about two-thirds as active as the unmodified chimera at 48 h but achieved full
      activity by 96 h in a neurite outgrowth assay in transfected PC12 cells.
      Elimination of only the two activation loop tyrosines (C bloc) also inactivated
      the receptor. All derivatives in which 4 (or 5) of the D bloc tyrosines were
      mutated were inactive in producing differentiation but showed low levels of
      kinase activity in in vitro assays. Derivatives in which 1, 2, or 3 tyrosines of
      the D bloc in different combinations were systematically changed demonstrated
      that 2 residues (Tyr(677) and Tyr(701), using hFGFR1 numbering) were essential
      for bioactivity, but the remaining 3 residues, including Tyr(766), the previously
      identified site for phospholipase C gamma (PLC gamma) activation, were not.
      Differentiation activity was paralleled by the activation (phosphorylation) of
      FRS2, SOS, and ERK1/2. PLC gamma activity was dependent on the presence of
      Tyr(766) but also required Tyr(677) and/or Tyr(701). Although fully active
      chimeras did not require PLC gamma, the responses of chimeras showing reduced
      activation of FRS2 were significantly enhanced by this activity. These results
      establish that PFR1 does not utilize any tyrosine residues, phosphorylated or
      not, to activate FRS2. However, it does require Tyr(677) and/or Tyr(701), which
      may function to stabilize the active conformation directly or indirectly.

PMID- 11459841
TI  - Differential Vicia villosa agglutinin reactivity identifies three distinct
      dystroglycan complexes in skeletal muscle.
AB  - We present evidence for the expression of three alpha-dystroglycan glycoforms in
      skeletal muscle cells, including two minor glycoforms marked by either patent or
      latent reactivity with the N-acetylgalactosamine-specific lectin Vicia villosa
      agglutinin. Both minor glycoforms co-isolated with beta-dystroglycan, but not
      with other dystrophin/utrophin-glycoprotein complex components, suggesting that
      they may perform distinct or modified cellular functions. We also confirmed that
      both patent and latent V. villosa agglutinin-reactive alpha-dystroglycan
      glycoforms are expressed in C2C12 myotubes. However, we found that the combined
      effect of saturating concentrations of V. villosa agglutinin and laminin-1 were
      strictly additive with respect to acetylcholine receptor cluster formation in
      C2C12 myotubes, which suggests that laminin-1 and V. villosa agglutinin do not
      compete for the same binding site on the cell surface. Finally, although beta-N
      acetylhexosaminidase digestion dramatically inhibited agrin-, V. villosa
      agglutinin-, and laminin-1-induced acetylcholine receptor clustering in C2C12
      myotubes, treatment with this enzyme had no effect on the amount of alpha
      dystroglycan that was bound to V. villosa agglutinin-agarose. We conclude that
      alpha-dystroglycan is not the V. villosa agglutinin receptor implicated in
      acetylcholine receptor cluster formation. However, our data provide new support
      for the hypothesis that different glycoforms of alpha-dystroglycan may perform
      distinct functions even within the same cell.

PMID- 11459842
TI  - Foot-and-mouth disease virus leader proteinase: involvement of C-terminal
      residues in self-processing and cleavage of eIF4GI.
AB  - The leader proteinase (L(pro)) of foot-and-mouth disease virus frees itself from
      the nascent polyprotein, cleaving between its own C terminus and the N terminus
      of VP4 at the sequence Lys-Leu-Lys- downward arrow-Gly-Ala-Gly. Subsequently, the
      L(pro) impairs protein synthesis from capped mRNAs in the infected cell by
      processing a host protein, eukaryotic initiation factor 4GI, at the sequence Asn
      Leu-Gly- downward arrow-Arg-Thr-Thr. A rabbit reticulocyte lysate system was used
      to examine the substrate specificity of L(pro) and the relationship of the two
      cleavage reactions. We show that L(pro) requires a basic residue at one side of
      the scissile bond to carry out efficient self-processing. This reaction is
      abrogated when leucine and lysine prior to the cleavage site are substituted by
      serine and glutamine, respectively. However, the cleavage of eIF4GI is unaffected
      by the inhibition of self-processing. Removal of the 18-amino acid C-terminal
      extension of L(pro) slowed eIF4GI cleavage; replacement of the C-terminal
      extension by unrelated amino acid sequences further delayed this cleavage.
      Surprisingly, wild-type L(pro) and the C-terminal variants all processed the
      polyprotein cleavage site in an intermolecular reaction at the same rate.
      However, when the polyprotein cleavage site was part of the same polypeptide
      chain as the wild-type Lb(pro), the rate of processing was much more rapid. These
      experiments strongly suggest that self-processing is an intramolecular reaction.

PMID- 11459843
TI  - The neurokinin A receptor activates calcium and cAMP responses through distinct
      conformational states.
AB  - G protein-coupled receptors are thought to mediate agonist-evoked signal
      transduction by interconverting between discrete conformational states endowed
      with different pharmacological and functional properties. In order to address the
      question of multiple receptor states, we monitored rapid kinetics of fluorescent
      neurokinin A (NKA) binding to tachykinin NK2 receptors, in parallel with
      intracellular calcium, using rapid mixing equipment connected to real time
      fluorescence detection. Cyclic AMP accumulation responses were also monitored.
      The naturally truncated version of neurokinin A (NKA-(4-10)) binds to the
      receptor with a single rapid phase and evokes only calcium responses. In
      contrast, full-length NKA binding exhibits both a rapid phase that correlates
      with calcium responses and a slow phase that correlates with cAMP accumulation.
      Furthermore, activators (phorbol esters and forskolin) and inhibitors (Ro 31-8220
      and H89) of protein kinase C or A, respectively, exhibit differential effects on
      NKA binding and associated responses; activated protein kinase C facilitates a
      switch between calcium and cAMP responses, whereas activation of protein kinase A
      diminishes cAMP responses. NK2 receptors thus adopt multiple activatable, active,
      and desensitized conformations with low, intermediate, or high affinities and
      with distinct signaling specificities.

PMID- 11459844
TI  - Elucidation of the differences between the 430- and 455-nm absorbing forms of
      P450-isocyanide adducts by resonance Raman spectroscopy.
AB  - Alkylisocyanide adducts of microsomal P450 exist in two interconvertible forms,
      each giving the Soret maximum around 430 or 455 nm. This is demonstrated with a
      rabbit liver P450 2B4. Resonance Raman spectra of the 430- and 455-nm forms were
      examined for typical P450s of the two types as well as for P450 2B4 because the
      430-nm form of P450 2B4 is liable to change into P420. P450cam and P450nor were
      selected as a model of the 430- and 455-nm forms, respectively. For the n-butyl
      isocyanide (CNBu) adduct, the Fe(II)-CNBu stretching band was observed for the
      first time at 480/467 cm(-1) for P450cam and at 471/459 cm(-1) for P450nor with
      their (12)CNBu/(13)CNBu derivatives. For P450cam, but not P450nor, other (13)C
      isotope-sensitive bands were observed at 412/402, 844/835, and 940/926 cm(-1).
      The C-N stretching mode was identified by Fourier transform IR spectroscopy at
      2116/2080 cm(-1) for P450cam and at 2148/2108 cm(-1) for P450nor for the
      (12)C/(13)C derivatives. These findings suggest that the binding geometry of
      isocyanide differs between the two forms-bent and linear structures for P450cam
      CNBu and P450nor-CNBu, respectively. In contrast, in the ferric state, the Raman
      (13)C isotopic frequency shifts, and the IR C-N stretching frequencies (2213/2170
      and 2215/2172 cm(-1)) were similar between P450cam and P450nor, suggesting
      similar bent structures for both.

PMID- 11459845
TI  - Identification of the enzymatic active site of tobacco caffeoyl-coenzyme A O
      methyltransferase by site-directed mutagenesis.
AB  - Animal catechol O-methyltransferases and plant caffeoyl-coenzyme A O
      methyltransferases share about 20% sequence identity and display common
      structural features. The crystallographic structure of rat liver catechol O
      methyltransferase was used as a template to construct a homology model for
      tobacco caffeoyl-coenzyme A O-methyltransferase. Integrating substrate
      specificity data, the three-dimensional model identified several amino acid
      residues putatively involved in substrate binding. These residues were mutated by
      a polymerase chain reaction method and wild-type and mutant enzymes were each
      expressed in Escherichia coli and purified. Substitution of Arg-220 with Thr
      resulted in the total loss of enzyme activity, thus indicating that Arg-220 is
      involved in the electrostatic interaction with the coenzyme A moiety of the
      substrate. Changes of Asp-58 to Ala and Gln-61 to Ser were shown to increase K(m)
      values for caffeoyl coenzyme A and to decrease catalytic activity. Deletions of
      two amino acid sequences specific for plant enzymes abolished activity. The
      secondary structures of the mutants, as measured by circular dichroism, were
      essentially unperturbed as compared with the wild type. Similar changes in
      circular dichroism spectra were observed after addition of caffeoyl coenzyme A to
      the wild-type enzyme and the substitution mutants but not in the case of deletion
      mutants, thus revealing the importance of these sequences in substrate-enzyme
      interactions.

PMID- 11459846
TI  - Thiocarboxylation of molybdopterin synthase provides evidence for the mechanism
      of dithiolene formation in metal-binding pterins.
AB  - Molybdopterin (MPT) is a pyranopterin with a unique dithiolene group coordinating
      molybdenum (Mo) or tungsten (W) in all Mo- and W-enzymes except nitrogenase. In
      Escherichia coli, MPT is formed by incorporation of two sulfur atoms into
      precursor Z, which is catalyzed by MPT synthase. The recently solved crystal
      structure of MPT synthase (Rudolph, M. J., Wuebbens, M. M., Rajagopalan, K. V.,
      and Schindelin, H. (2000) Nat. Struct. Biol. 8, 42-46) shows the heterotetrameric
      nature of the enzyme that is composed of two small (MoaD) and two large subunits
      (MoaE). According to sequence and structural similarities among MoaD, ubiquitin,
      and ThiS, a thiocarboxylation of the C terminus of MoaD is proposed that would
      serve as the source of sulfur that is transferred to precursor Z. Here, we
      describe the in vitro generation of carboxylated and thiocarboxylated MoaD. Both
      forms of MoaD are monomeric and are able to form a heterotetrameric complex after
      coincubation in equimolar ratios with MoaE. Only the thiocarboxylated MPT
      synthase complex was found to be able to convert precursor Z in vitro to MPT.
      Slight but significant differences between the carboxylated and the
      thiocarboxylated MPT synthase can be seen using size exclusion chromatography. A
      two-step reaction of MPT synthesis is proposed where the dithiolene is generated
      by two thiocarboxylates derived from a single tetrameric MPT synthase.

PMID- 11459847
TI  - NAD+-dependent DNA ligase encoded by a eukaryotic virus.
AB  - We report the production, purification, and characterization of an NAD(+)
      dependent DNA ligase encoded by the Amsacta moorei entomopoxvirus (AmEPV), the
      first example of an NAD(+) ligase from a source other than eubacteria. AmEPV
      ligase lacks the zinc-binding tetracysteine domain and the BRCT domain that are
      present in all eubacterial NAD(+) ligases. Nonetheless, the monomeric 532-amino
      acid AmEPV ligase catalyzed strand joining on a singly nicked DNA in the presence
      of a divalent cation and NAD(+). Neither ATP, dATP, nor any other nucleoside
      triphosphate could substitute for NAD(+). Structure probing by limited
      proteolysis showed that AmEPV ligase is punctuated by a surface-accessible loop
      between the nucleotidyltransferase domain, which is common to all ligases, and
      the N-terminal domain Ia, which is unique to the NAD(+) ligases. Deletion of
      domain Ia of AmEPV ligase abolished the sealing of 3'-OH/5'-PO(4) nicks and the
      reaction with NAD(+) to form ligase-adenylate, but had no effect on
      phosphodiester formation at a pre-adenylated nick. Alanine substitutions at
      residues within domain Ia either reduced (Tyr(39), Tyr(40), Asp(48), and Asp(52))
      or abolished (Tyr(51)) sealing of a 5'-PO(4) nick and adenylyl transfer from
      NAD(+) without affecting ligation of DNA-adenylate. We conclude that: (i) NAD(+)
      dependent ligases exist in the eukaryotic domain of the phylogenetic tree; and
      (ii) ligase structural domain Ia is a determinant of cofactor specificity and is
      likely to interact directly with the nicotinamide mononucleotide moiety of
      NAD(+).

PMID- 11459848
TI  - Structural characterization of human recombinant and bone-derived bone
      sialoprotein. Functional implications for cell attachment and hydroxyapatite
      binding.
AB  - Human bone sialoprotein (BSP) comprises 15% of the total noncollagenous proteins
      in bone and is thought to be involved in bone mineralization and remodeling.
      Recent data suggest a role for BSP in breast cancer and the development of bone
      metastases. We have produced full-length recombinant BSP in a human cell line and
      purified the protein from human bone retaining the native structure with proper
      folding and post-translational modifications. Mass spectrometry of bone-derived
      BSP revealed an average mass of 49 kDa and for recombinant BSP 57 kDa. The post
      translational modifications contribute 30-40%. Carbohydrate analysis revealed 10
      different complex-type N-glycans on both proteins and eight different O-glycans
      on recombinant BSP, four of those were found on bone-derived BSP. We could
      identify eight threonines modified by O-glycans, leaving the C terminus of the
      protein free of glycans. The recombinant protein showed similar secondary
      structures as bone-derived BSP. BSP was visualized in electron microscopy as a
      globule linked to a thread-like structure. The affinity for hydroxyapatite was
      higher for bone-derived BSP than for recombinant BSP. Cell adhesion assays showed
      that the binding of BSP to cells can be reversibly diminished by denaturation.

PMID- 11459849
TI  - The verprolin-like central (vc) region of Wiskott-Aldrich syndrome protein
      induces Arp2/3 complex-dependent actin nucleation.
AB  - Wiskott-Aldrich Syndrome protein (WASp) and related proteins stimulate actin
      filament nucleation by Arp2/3 complex. The isolated C-terminal VCA domain of WASp
      (containing Verprolin-like, Central and Acidic regions) is constitutively active
      but autoinhibited in the full-length protein. This study compared the ability of
      parts of VCA fused to the C terminus of glutathione S-transferase (GST) to bind
      actin and Arp2/3 complex in vitro and to activate actin polymerization in vitro
      and in cells. Fluorescence anisotropy measurements showed that GST-CA and GST-A
      bound Arp2/3 complex with K(d) values of 0.11 microm and 1.0 microm,
      respectively, whereas GST-VC displayed almost undetectable binding (K(d) > 1 mm).
      However, GST-VC activated actin nucleation through Arp2/3 complex in vitro,
      though requiring 70-fold higher concentration than GST-VCA while neither GST-CA
      nor GST-A activated Arp2/3 complex in vitro, though both GST-CA and GST-A
      inhibited Arp2/3 complex activation by WASp VCA. None of these constructs bound
      WASp from macrophage lysates. Both GST-VC and GST-CA induced actin accumulations
      when microinjected into primary human macrophages or human endothelial vein
      cells. However, only microinjection of GST-VC led to a significant increase of
      cellular polymerized actin. Additionally, endogenous Arp2/3 complex, but not
      WASp, colocalized with these GST-VC-induced actin accumulations. These data
      suggest that WASp constructs lacking the A region, previously thought to be
      indispensable for actin nucleation, are able to bind and activate Arp2/3 complex
      in vitro and in vivo.

PMID- 11459850
TI  - The multifaceted mechanisms of estradiol and estrogen receptor signaling.

PMID- 11459851
TI  - Orphan nuclear receptors: the exotics of xenobiotics.

PMID- 11459852
TI  - PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth.

PMID- 11459853
TI  - Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism.

PMID- 11459854
TI  - Coregulator codes of transcriptional regulation by nuclear receptors.

PMID- 11459855
TI  - Nuclear receptor minireview series.

PMID- 11459857
TI  - Angiogenic heterogeneity: regulation of neoplastic angiogenesis by the organ
      microenvironment.

PMID- 11459858
TI  - Lung epithelial proliferation: a biomarker for chemoprevention trials?

PMID- 11459859
TI  - Cancer vaccines: advances give hope for future therapy.

PMID- 11459860
TI  - Corporate partnerships aiding cancer vaccine development.

PMID- 11459861
TI  - Spontaneous regression of melanoma may offer insight into cancer immunology.

PMID- 11459862
TI  - Stat bite: Estimated 2000 lung cancer incidence in males in selected countries.

PMID- 11459863
TI  - What ever happened to...? Looking back 10 years.

PMID- 11459864
TI  - International clinical trial recommendations released.

PMID- 11459865
TI  - Bisphosphonates may be useful in treatment of bone metastases.

PMID- 11459866
TI  - Phases of biomarker development for early detection of cancer.

PMID- 11459867
TI  - Blocking oncogenic Ras signaling for cancer therapy.
AB  - The Ras gene product is a monomeric membrane-localized G protein of 21 kd that
      functions as a molecular switch linking receptor and nonreceptor tyrosine kinase
      activation to downstream cytoplasmic or nuclear events. Each mammalian cell
      contains at least three distinct ras proto-oncogenes encoding closely related,
      but distinct proteins. Activating mutations in these Ras proteins result in
      constitutive signaling, thereby stimulating cell proliferation and inhibiting
      apoptosis. Oncogenic mutations in the ras gene are present in approximately 30%
      of all human cancers. K-ras mutations occur frequently in non-small-cell lung,
      colorectal, and pancreatic carcinomas; H-ras mutations are common in bladder,
      kidney, and thyroid carcinomas; N-ras mutations are found in melanoma,
      hepatocellular carcinoma, and hematologic malignancies. The ras-signaling pathway
      has attracted considerable attention as a target for anticancer therapy because
      of its important role in carcinogenesis. In this review, the physiologic and
      biochemical properties of the Ras proteins, their mechanism of cell signaling,
      and their relation to human cancer will be discussed. Novel cancer therapeutic
      approaches based on the inhibition of Ras-mediated signaling, including
      inhibition of Ras processing, inhibition of Ras protein synthesis, and blockage
      of downstream Ras effectors, will be discussed.

PMID- 11459868
TI  - Heterogeneity of angiogenic activity in a human liposarcoma: a proposed mechanism
      for "no take" of human tumors in mice.
AB  - BACKGROUND: Tumor cells are known to be heterogeneous with respect to their
      metastatic activity, proliferation rate, and activity of several enzymes.
      However, little is known about the heterogeneity of tumor angiogenic activity. We
      investigated whether heterogeneity of angiogenic activity could be responsible
      for the well-known observation of "no take" of human tumors transplanted into
      immunodeficient mice. METHODS: Severe combined immunodeficient (SCID) mice were
      xenotransplanted subcutaneously with tumor tissue (n = 55) or cell suspension of
      a human liposarcoma cell line (SW-872) or subclones (n = 28), with varying cell
      proliferation rates. Xenograft tumor growth was recorded for up to 6 months.
      Tumor tissues were then removed and analyzed for tumor cell apoptosis,
      microvessel density, and cell proliferation. All statistical tests were two
      sided. RESULTS: Pieces of tumor derived from the parental cell line or its clones
      gave rise to three kinds of tumors: 1) highly angiogenic and fast-growing
      (aggressive) tumors, 2) weakly angiogenic and slow-growing tumors, and 3)
      nonangiogenic and stable tumors. Most tumors retained the original phenotype of
      their parental tumor. Tumor volume correlated positively with microvessel density
      (Spearman correlation coefficient [r] =.89; P< or =.0001) and inversely with
      tumor cell apoptosis (Spearman r = -.68; P =.002). Tumor volume was less strongly
      but still positively correlated with tumor cell proliferation in vivo (Spearman r
      =.55; P =.02). CONCLUSIONS: Human liposarcoma cells appear to be heterogeneous in
      their angiogenic activity. When tumor cells with little or no angiogenic activity
      are transplanted into SCID mice, a microscopic, dormant tumor results that may
      not grow further. Because such tiny tumors are neither grossly visible nor
      palpable, they have previously been called "no take." The finding that an
      angiogenic tumor can contain subpopulations of tumor cells with little or no
      angiogenic activity may provide a novel mechanism for dormant micrometastases,
      late recurrence, and changes in rate of tumor progression.

PMID- 11459869
TI  - Long-term impact of smoking on lung epithelial proliferation in current and
      former smokers.
AB  - BACKGROUND: Lung cancer risk remains elevated for many years after quitting
      smoking. To assess using proliferation indices in bronchial tissues as an
      intermediate endpoint biomarker in lung cancer chemoprevention trials, we
      determined the relationship between the extent, intensity, and cessation of
      tobacco smoking and proliferative changes in bronchial epithelial biopsy
      specimens. METHODS: Bronchial biopsy specimens were obtained from up to six
      epithelial sites in 120 current smokers (median pack-years, 42) and 207 former
      smokers (median pack-years, 40; median quit-years, 8.1). Sections from the
      paraffin-embedded specimens were stained with hematoxylin--eosin to determine the
      metaplasia index and with an antibody to Ki-67 to determine the proliferative
      (labeling) index for the basal and parabasal (Ki-67 PLI) layers. All statistical
      tests were two-sided. RESULTS: Biopsy sites with metaplasia had statistically
      significantly higher Ki-67-labeling indices than those without metaplasia
      (P<.001) in both current and former smokers. Increased proliferation was observed
      in multiple biopsy sites, with the average Ki-67 PLI of the subject strongly
      correlating with the metaplasia index (r =.72 for current smokers; P<.001), even
      in sites without metaplasia (r =.23 for current smokers; P<.001). In current
      smokers, the Ki-67 PLI was associated with the number of packs smoked/day (P
      =.02) but not with smoking years or pack-years. In subjects who had quit smoking,
      the Ki-67 PLI dropped statistically significantly within 1 year (P =.008) but
      remained detectable for more than 20 years, even in the absence of squamous
      metaplasia. CONCLUSION: Smoking appears to elicit a dose-related proliferative
      response in the bronchial epithelia of active smokers. Although the proliferative
      response decreased gradually in former smokers, a subset of individuals had
      detectable proliferation for many years and may benefit from targeted
      chemoprevention. Bronchial epithelial proliferation, measured by Ki-67, may
      provide a useful biomarker in the assessment of lung cancer risk and in the
      response to chemopreventive interventions.

PMID- 11459870
TI  - Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective
      Italian study.
AB  - BACKGROUND: The relationship between erythrocyte membrane fatty acids and
      postmenopausal breast cancer risk was analyzed previously only by retrospective
      studies, which suggested a protective effect of increased saturation index (SI),
      i.e., the ratio of membrane stearic to oleic acid. We investigated the
      relationships in a prospective study of hormones, diet, and prediagnostic breast
      cancer (the ORDET study) conducted in northern Italy. METHODS: A total of 4052
      postmenopausal women were followed for an average of 5.5 years; 71 cases of
      invasive breast cancer were identified. For each case subject, two matched
      control subjects were chosen randomly from among cohort members. The various
      fatty acids in erythrocyte membranes were measured as a percentage of total fatty
      acids. Conditional logistic regression analysis evaluated the association between
      membrane fatty acid composition and breast cancer risk. The SI, which is
      influenced by the activity of the enzyme delta 9 desaturase (Delta 9-d), was also
      investigated. All statistical tests were two-sided. RESULTS: Oleic (highest
      versus lowest tertile of percentage of total fatty acids, odds ratio [OR] = 2.79;
      95% confidence interval [CI] = 1.24 to 6.28) and monounsaturated fatty acids
      (highest to lowest tertile, OR = 5.21; 95% CI = 1.95 to 13.91) were positively
      associated with breast cancer risk. The SI (highest to lowest tertile, OR = 0.29;
      95% CI = 0.13 to 0.64) was inversely associated with breast cancer risk. The
      analysis suggested an inverse association between total polyunsaturated fatty
      acids and breast cancer risk, but individual polyunsaturated fatty acids behaved
      differently. There was no association between saturated fatty acids and breast
      cancer risk. CONCLUSIONS: We have found that monounsaturated fats and SI in
      erythrocyte membranes are predictors of postmenopausal breast cancer. Both of
      these variables depend on the activity of the enzyme Delta 9-d. The dietary,
      metabolic, and hormonal factors acting on Delta 9-d expression and activity and,
      therefore, on patterns of fatty acid metabolism, should be further investigated
      as possible determinants of breast cancer.

PMID- 11459871
TI  - Magnetic resonance imaging and mammography in women with a hereditary risk of
      breast cancer.
AB  - BACKGROUND: Although breast cancer screening is recommended to start at a younger
      age for women with a hereditary risk of breast cancer, the sensitivity of
      mammography for these women is reduced. We compared magnetic resonance imaging
      (MRI) with mammography to determine which is more sensitive and whether MRI could
      play a role in the early detection of breast cancer for these women. METHODS: We
      constructed a retrospective cohort of all breast MRI and mammography surveillance
      reports made in our department from November 1994 to February 2001. All of the
      179 women in the cohort had received biannual palpation in addition to annual
      imaging by MRI, mammography, or both. The 258 MRI images and the 262 mammograms
      were classified with the use of the BI-RADS (i.e., Breast Imaging Reporting and
      Data System) scoring system, which has five categories to indicate the level of
      suspicion of a lesion. Receiver operator characteristic curves were generated for
      MRI and mammography, and the area under each curve (AUC) was assessed for the
      entire cohort of 179 women and for a subset of 75 women who had received both an
      MRI and a mammographic examination within a 4-month period. All statistical tests
      were two-sided. RESULTS: In the cohort of 179 women, we detected 13 breast
      cancers. Seven cancers were not revealed by mammography, but all were detected by
      MRI. For the entire cohort, the AUC for mammography was 0.74 (95% confidence
      interval [CI] = 0.68 to 0.79), and the AUC for MRI was 0.99 (95% CI = 0.98 to
      1.0). For the subset of women who had both examinations, the AUC for mammography
      was 0.70 (95% CI = 0.60 to 0.80), and the AUC for MRI was 0.98 (95% CI = 0.95 to
      1.0). CONCLUSION: MRI was more accurate than mammography in annual breast cancer
      surveillance of women with a hereditary risk of breast cancer. Larger prospective
      studies to examine the role of MRI in screening programs are justified.

PMID- 11459872
TI  - Induction of atypical ductal hyperplasia in mouse mammary gland organ culture.

PMID- 11459873
TI  - Cyclin D1 polymorphism and increased risk of colorectal cancer at young age.

PMID- 11459874
TI  - Re: Prostate cancer incidence and mortality in the United States and the United
      Kingdom.

PMID- 11459875
TI  - Chemoprevention or antichemoprevention? A salutary warning From the beta-carotene
      experience.

PMID- 11459877
TI  - Regeneration of dopaminergic function in 6-hydroxydopamine-lesioned rats by
      neuroimmunophilin ligand treatment.
AB  - Nonimmunosuppressant immunophilin ligands have been found previously to stimulate
      neurite growth in culture and to promote regeneration of peripheral and central
      nerve fibers in vivo. To further characterize the effectiveness of these ligands,
      we have investigated the effect of the immunophilin ligand GPI-1046 in 6
      hydroxydopamine (6-OHDA)-lesioned rats. In unlesioned rats, tetanic stimulation
      of the white matter induced long-term potentiation (LTP) of corticostriatal
      synaptic transmission as indicated by a 40-100% increase in the field potential
      amplitudes recorded in striatal brain slices. Unilateral microinjection of 6-OHDA
      into the substantia nigra resulted in a loss of corticostriatal LTP and in
      significant abnormality of motor behavior as assessed by amphetamine-induced
      ipsilateral rotations. Daily treatment of 6-OHDA-lesioned rats with GPI-1046 (10
      mg/kg, s.c.) for 1 week reduced amphetamine-induced rotations by 75% and greatly
      restored the striatal tyrosine hydroxylase immunostaining. In addition, GPI-1046
      almost completely restored corticostriatal LTP in 6-OHDA-lesioned animals. LTP in
      normal animals and that restored by GPI-1046 in lesioned animals were both
      blocked by the NMDA receptor antagonist APV, suggesting mediation by NMDA
      receptors. Both LTPs were sensitive to dopamine (DA) receptor antagonists. The
      nonselective DA receptor antagonist chlorpromazine and the selective D1-D5
      receptor antagonist SCH23390 reduced the LTP by 90%. These results demonstrate
      that the immunophilin ligand GPI-1046 can reverse the abnormalities in the
      substantia nigra-striatal dopaminergic system that are caused by 6-OHDA, thus
      providing a potential therapeutic agent for Parkinson's disease.

PMID- 11459878
TI  - Repetitive transcranial magnetic stimulation of the human prefrontal cortex
      induces dopamine release in the caudate nucleus.
AB  - Dopamine is implicated in movement, learning, and motivation, and in illnesses
      such as Parkinson's disease, schizophrenia, and drug addiction. Little is known
      about the control of dopamine release in humans, but research in experimental
      animals suggests that the prefrontal cortex plays an important role in regulating
      the release of dopamine in subcortical structures. Here we used [(11)C]raclopride
      and positron emission tomography to measure changes in extracellular dopamine
      concentration in vivo after repetitive transcranial magnetic stimulation (rTMS)
      of the dorsolateral prefrontal cortex in healthy human subjects. Repetitive TMS
      of the left dorsolateral prefrontal cortex caused a reduction in
      [(11)C]raclopride binding in the left dorsal caudate nucleus compared with rTMS
      of the left occipital cortex. There were no changes in binding in the putamen,
      nucleus accumbens, or right caudate. This shows that rTMS of the prefrontal
      cortex induces the release of endogenous dopamine in the ipsilateral caudate
      nucleus. This finding has implications for the therapeutic and research use of
      rTMS in neurological and psychiatric disorders.

PMID- 11459879
TI  - Spatial distribution of low- and high-voltage-activated calcium currents in
      neurons of the deep cerebellar nuclei.
AB  - The spatial distribution of low-voltage-activated (LVA) and high-voltage
      activated (HVA) barium currents was investigated in neurons of the deep
      cerebellar nuclei (DCN) by combining barium imaging with voltage clamp. The
      current-induced fluorescence signal (DeltaF/F) of the HVA current was five times
      higher then the LVA-induced signal at the soma, but both signals were
      approximately equal in size in distant dendrites. This position-dependent shift
      of DeltaF/F indicates a non-uniform distribution of the underlying calcium
      channels. The higher weight of the LVA signal in the dendrites suggests that the
      LVA might be of particular relevance for the dendritic integration of synaptic
      inputs.

PMID- 11459880
TI  - Anticipation of increasing monetary reward selectively recruits nucleus
      accumbens.
AB  - Comparative studies have implicated the nucleus accumbens (NAcc) in the
      anticipation of incentives, but the relative responsiveness of this neural
      substrate during anticipation of rewards versus punishments remains unclear.
      Using event-related functional magnetic resonance imaging, we investigated
      whether the anticipation of increasing monetary rewards and punishments would
      increase NAcc blood oxygen level-dependent contrast (hereafter, "activation") in
      eight healthy volunteers. Whereas anticipation of increasing rewards elicited
      both increasing self-reported happiness and NAcc activation, anticipation of
      increasing punishment elicited neither. However, anticipation of both rewards and
      punishments activated a different striatal region (the medial caudate). At the
      highest reward level ($5.00), NAcc activation was correlated with individual
      differences in self-reported happiness elicited by the reward cues. These
      findings suggest that whereas other striatal areas may code for expected
      incentive magnitude, a region in the NAcc codes for expected positive incentive
      value.

PMID- 11459881
TI  - Restless legs syndrome.

PMID- 11459882
TI  - Are two heads better than one?

PMID- 11459883
TI  - Diagnosis of chronic peripheral neuropathy.

PMID- 11459884
TI  - Ramsay Hunt syndrome.
AB  - The strict definition of the Ramsay Hunt syndrome is peripheral facial nerve
      palsy accompanied by an erythematous vesicular rash on the ear (zoster oticus) or
      in the mouth. J Ramsay Hunt, who described various clinical presentations of
      facial paralysis and rash, also recognised other frequent symptoms and signs such
      as tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. He explained
      these eighth nerve features by the close proximity of the geniculate ganglion to
      the vestibulocochlear nerve within the bony facial canal. Hunt's analysis of
      clinical variations of the syndrome now bearing his name led to his recognition
      of the general somatic sensory function of the facial nerve and his defining of
      the geniculate zone of the ear. It is now known that varicella zoster virus (VZV)
      causes Ramsay Hunt syndrome. Compared with Bell's palsy (facial paralysis without
      rash), patients with Ramsay Hunt syndrome often have more severe paralysis at
      onset and are less likely to recover completely. Studies suggest that treatment
      with prednisone and acyclovir may improve outcome, although a prospective
      randomised treatment trial remains to be undertaken. In the only prospective
      study of patients with Ramsay Hunt syndrome, 14% developed vesicles after the
      onset of facial weakness. Thus, Ramsay Hunt syndrome may initially be
      indistinguishable from Bell's palsy. Further, Bell's palsy is significantly
      associated with herpes simplex virus (HSV) infection. In the light of the known
      safety and effectiveness of antiviral drugs against VZV or HSV, consideration
      should be given to early treatment of all patients with Ramsay Hunt syndrome or
      Bell's palsy with a 7-10 day course of famciclovir (500 mg, three times daily) or
      acyclovir (800 mg, five times daily), as well as oral prednisone (60 mg daily for
      3-5 days). Finally, some patients develop peripheral facial paralysis without ear
      or mouth rash, associated with either a fourfold rise in antibody to VZV or the
      presence of VZV DNA in auricular skin, blood mononuclear cells, middle ear fluid,
      or saliva. This indicates that a proportion of patients with "Bell's palsy" have
      Ramsay Hunt syndrome zoster sine herpete. Treatment of these patients with
      acyclovir and prednisone within 7 days of onset has been shown to improve the
      outcome of recovery from facial palsy.

PMID- 11459885
TI  - How does the degree of carotid stenosis affect the accuracy and interobserver
      variability of magnetic resonance angiography?
AB  - OBJECTIVES: The accuracy of magnetic resonance angiography (MRA) was determined
      in patients with recently symptomatic tight (80%-99%) carotid stenosis (on
      Doppler ultrasound), and the effect of stenosis severity on the accuracy and
      interobserver variability of MRA was studied. METHODS: Forty four consecutive
      patients undergoing intra-arterial angiography (IAA) before carotid
      endarterectomy were prospectively studied, in two centres with identical MR
      scanners and sequences. All patients had undergone Doppler ultrasound, showing a
      70% or worse carotid stenosis on the symptomatic side. MRA and IAA were done
      during the same admission. The MRA films were each independently and blindly read
      for percentage stenosis (signal gap if present) by four observers. The IA
      angiograms were read separately by one observer, blind to symptoms, and Doppler
      and MRA results. RESULTS: Signal gaps on MRA were seen in stenoses ranging from
      67% to 99% on intra-arterial angiography. Magnetic resonance angiograms
      consistently overestimated the percentage stenosis according to intra-arterial
      angiography. Clinically significant misclassification of stenosis occurred
      according to MRA in 7% of patients, and was more frequent as carotid stenosis
      increased. CONCLUSION: Significant diagnostic errors occur with MRA in patients
      with tight carotid stenosis. Any morbidity occurring as a result of
      misclassification by MRA is likely to be offset by the avoidance of
      complications; however, this could only be determined with certainty in a
      randomised controlled trial.

PMID- 11459886
TI  - Functional magnetic resonance imaging of working memory impairment after
      traumatic brain injury.
AB  - OBJECTIVES: To examine patterns of brain activation while performing a working
      memory task in persons with moderate to severe traumatic brain injury (TBI) and
      healthy controls. It is well established that working memory is an area of
      cognition that is especially vulnerable to disruption after TBI. Although much
      has been learned about the system of cerebral representation of working memory in
      healthy people, little is known about how this system is disrupted by TBI.
      METHODS: Functional magnetic resonance imaging (fMRI) was used to assess brain
      activation during a working memory task (a modified version of the paced auditory
      serial addition test) in nine patients with TBI and seven healthy controls.
      RESULTS: Patients with TBI were able to perform the task, but made significantly
      more errors than healthy controls. Cerebral activation in both groups was found
      in similar regions of the frontal, parietal, and temporal lobes, and resembled
      patterns of activation found in previous neuroimaging studies of working memory
      in healthy persons. However, compared with the healthy controls, the TBI group
      displayed a pattern of cerebral activation that was more regionally dispersed and
      more lateralised to the right hemisphere. Differences in lateralisation were
      particularly evident in the frontal lobes. CONCLUSIONS: Impairment of working
      memory in TBI seems to be associated with alterations in functional cerebral
      activity.

PMID- 11459887
TI  - Microdialytical monitoring of uric and ascorbic acids in the brains of patients
      after severe brain injury and during neurovascular surgery.
AB  - OBJECTIVES: Microdialysis has been extensively used to monitor brain metabolism
      in the extracellular fluid of patients with severe head injury, to detect the
      onset of secondary ischaemic damage. The aim was to investigate whether
      concentrations of uric and ascorbic acids were altered in such patients. Both
      these compounds play a part in free radical metabolism, which is accelerated
      after ischaemia and brain injury. METHODS: Patients with aneurysm or bypass
      operations were monitored intraoperatively to assess concentrations in minimally
      disturbed tissue. Afterwards, 13 patients with severe head trauma were monitored
      for up to 13 days in the intensive care unit. RESULTS: Intraoperatively,
      concentrations of both ascorbic and uric acids were significantly higher in the
      bypass group than in patients with aneurysm, which might be attributed to chronic
      ischaemic conditions caused by the unilateral occlusion of the carotid artery. In
      the patients with trauma, mean values of uric acid, varying between 6 microM and
      180 microM, did not correlate with type of injury (contusion or diffuse) or
      duration of monitoring time. Patients who died had significantly higher
      concentrations of uric acid than those with a good outcome. Ascorbic acid could
      be detected only intermittently, probably due to technical problems.
      Concentrations of these two compounds could not be correlated with clinical
      findings during the course of monitoring. CONCLUSIONS: Although uric and ascorbic
      acids are influenced by ischaemic conditions-for example, in bypass patients,
      neither compound is suitable for monitoring for free radical activity after
      severe head injury. Patients with a bad outcome tended to have higher
      concentrations of uric acid.

PMID- 11459888
TI  - Fixed and dilated pupils after trauma, stroke, and previous intracranial surgery:
      management and outcome.
AB  - OBJECTIVES: To clarify whether different causative events (trauma, stroke,
      intracranial surgery), time of intervention, and treatment mode influence
      outcome, patients with fixed and dilated pupils (FDPs) in a prospective
      neurosurgical series were evaluated. METHODS: Ninety nine consecutive patients
      who presented with or developed one or two FDPs, were split into three groups
      according to the respective aetiology: 46 patients had a trauma, 41 patients a
      stroke (subarachnoid or intracerebral haemorrhage), and 12 patients had undergone
      previous elective intracranial surgery. Appropriate therapy was performed
      depending on the CT findings. Outcome was classified according to the Glasgow
      outcome scale (GOS). RESULTS: Overall mortality was 75%. In 15% outcome was
      unfavourable (GOS 2 and 3), and in 10% favourable (GOS 4, 5) at 24 month follow
      up. No differences in outcome were found between trauma, stroke, and postelective
      surgery groups. Unilaterally FDP was associated with a better chance of survival
      (46% v 13%; p<0.01). Age did not correlate with survival, but younger survivors
      had a significantly better outcome. Patients in whom an intracranial mass was
      removed surgically had a 42% survival rate, compared with 8% with conservative
      treatment (p<0.01). Patients with a shorter delay from FDPs to intervention had a
      better chance of recovery after trauma and previous intracranial surgery
      (p<0.05). No patient survived better than a vegetative state, if previous FDPs
      did not become reactive shortly after therapy. If both pupils became reactive on
      therapy, the chance of survival was 62%. Of these survivors 42% had a favourable
      outcome. CONCLUSION: Bilateral restoration of pupillary reactivity shortly after
      therapy is crucial for survival. Surgical evacuation of an intracranial mass,
      unilateral FDPs, early intervention, and younger age are related to better
      chances of survival or recovery. The prognosis of patients with FDPs after
      trauma, stroke, and previous elective intracranial surgery is similar.

PMID- 11459889
TI  - Acute care in neurosurgery: quantity, quality, and challenges.
AB  - OBJECTIVE: Part of the daily routine in neurosurgery is the treatment of
      emergency room admissions, and acute cases from other departments or from outside
      hospitals. This acute care is not normally included in performance figures or
      budget management, nor analysed scientifically in respect of quantity and quality
      of care provided by neurosurgeons. METHOD: Over a 1 year period, all acute care
      cases managed by two neurosurgical on call teams in a large northern German city,
      were recorded prospectively on a day by day basis. A large database of 1819
      entries was created and analysed using descriptive statistics. RESULTS: The
      minimum incidence of patients requiring neurosurgical acute care was estimated to
      be 75-115/100 000 inhabitants/year. This corresponds to a mean of about 6/day.
      Only 30% of patients came directly via the emergency room. The fate of 70% of
      patients depended initially on the "neurosurgical qualification" of primary care
      doctors and here deficits existed. Although most intracerebral and subarachnoid
      haemorrhages were managed with the participation of neurosurgeons, they were not
      involved in the management of most mild and moderate traumatic brain injuries.
      Within 1 year the additional workload from acute care amounted to 1000 unplanned
      admissions, 900 acute imaging procedures, and almost 400 emergency operations.
      CONCLUSION: The current policy in public health, which includes cuts in
      resources, transport facilities, and manpower, is not compatible with the
      demonstrated extent of acute neurosurgical care. In addition to routine elective
      work, many extra admissions, evening or night time surgery, and imaging
      procedures have to be accomplished. An education programme for generalists is
      required to improve overall patient outcome. These conclusions hold special
      importance if health authorities wish to not only maintain present standards but
      aim to improve existing deficits.

PMID- 11459890
TI  - Ultrastructural and immunocytochemical evidence that an incompetent blood-brain
      barrier is related to the pathophysiology of cavernous malformations.
AB  - OBJECTIVES: Cerebral cavernous malformations are linked to mutations of the KRIT1
      gene at the CCM1 locus and to mutations at two other loci, CCM2 and CCM3, for
      which genes are not yet identified. There is little information regarding the
      function of KRIT1. Histological and immunocytochemical analysis of cavernous
      malformations have not shed much light on their pathophysiology. METHODS:
      Morphological analysis of cavernous malformations was extended to the
      ultrastructural level by examining lesions from two patients by
      immunocytochemistry and electron microscopy. RESULTS: The lesions consisted of
      endothelial lined vascular sinusoids embedded in a collagen matrix. Nuclei
      belonging to cells distinct from endothelial cells were rare. The basal lamina of
      the endothelial cells consisted focally of multiple layers. No tight junctions at
      endothelial cell interfaces were found; however, several examined endothelial
      cell interfaces demonstrated apparent gaps between endothelial cell processes
      where basal lamina was exposed directly to the lumen of the sinusoids. Heavy
      hemosiderin deposits were found underlying the vascular channels within microns
      of the basal lamina without evidence of disrupted vessels. No astrocytic foot
      processes were seen within lesions. Glial fibrillary acidic protein
      immunocytochemistry confirmed that astrocyte processes stopped at the border of
      the lesions. CONCLUSIONS: The absence of blood-brain barrier components may lead
      to leakage of red blood cells into these lesions and the surrounding brain in the
      absence of major haemorrhage, thus accounting for the propensity of cavernous
      malformations to cause seizures. These data also raise the possibility that KRIT1
      plays a part in the formation of endothelial cell junctions and expression of a
      mature vascular phenotype.

PMID- 11459891
TI  - Health related quality of life is improved by botulinum neurotoxin type A in long
      term treated patients with focal dystonia.
AB  - OBJECTIVES: The advent of botulinum neurotoxin type A (BoNT/A) gave rise to
      substantial progress in the treatment of focal dystonias. In the light of the
      high costs of the toxin and the necessity to establish valid outcome indices for
      this treatment apart from sheer reduction of dystonic muscle tone and posture,
      the impact of focal dystonia and its treatment with BoNT/A on patients' health
      related quality of life (HRQL) was determined. METHODS: Fifty patients with
      cranial and cervical dystonia treated long term with BoNT/A were enrolled in a
      prospective, open labelled cohort study. The HRQL was assessed using the EuroQol
      (EQ-5D) and the short form 36 health survey questionnaire (SF-36) at baseline
      before BoNT/A injections and at two follow up visits after 6 and 12 weeks
      covering one BoNT/A treatment period with maximum effect size at the first follow
      up. RESULTS: Compared with a general population sample, a considerable negative
      impact of focal dystonia on HRQL was found in patients under investigation. In
      both disease types, BoNT/A treatment led to a significant improvement in several
      HRQL dimensions, in particular providing moderate to marked effect sizes in the
      fields of mental health and pain. The impairment of HRQL due to pain as well as
      the BoNT/A induced improvement within this SF-36 subscore were significantly
      higher in patients with cervical dystonia. Under BoNT/A therapy, no correlation
      was found between changes of clinical outcome scores and HRQL measures.
      CONCLUSIONS: The data confirm that BoNT/A is able to induce a significant, but
      temporary amelioration of several aspects of HRQL in both types of focal
      dystonia. This may substantially contribute to the patients' subjective benefit
      from the therapy. Moreover, the data provide further arguments to accept high
      costs of the BoNT/A treatment in these severely handicapped patients, as a
      consequence of its considerable benefit on quality of life.

PMID- 11459892
TI  - Peripheral neuropathy in chronic occupational inorganic lead exposure: a clinical
      and electrophysiological study.
AB  - BACKGROUND AND OBJECTIVES: Traditionally the neuromuscular disorder associated
      with lead poisoning has been purely motor. This study assessed peripheral nerve
      function clinically and electrophysiologically in 46 patients with neuropathic
      features out of a total population of 151 workers with raised blood and/or
      urinary lead concentrations. RESULTS: Average duration of occupational exposure
      for the neuropathic group ranged from 8-47 years (mean 21.7). Their mean blood
      lead concentration (SD) was 63.9 (18.3) microg/dl (normal <40), urinary lead 8.6
      (3.3) microg/dl (normal<5.0), urinary coproporphyrins 66.7 (38.4) microg/g
      creatinine (20-80), urinary aminolaevulinic acid 1.54 (0.39) mg/g creatinine (0.5
      2.5). All 46 had distal paraesthesiae, pain, impaired pin prick sensation,
      diminished or absent ankle jerks, and autonomic vasomotor or sudomotor
      disturbances. Reduced vibration sensation and postural hypotension were present
      in all 20 studied. None of these 46 patients had motor abnormalities. Motor
      conduction velocity and compound muscle action potential amplitudes were normal,
      with marginally prolonged distal motor latencies. Sensory nerve action potential
      amplitudes lay at the lower end of the normal range, and the distal sensory
      latencies were prolonged. No direct correlation was found between the biochemical
      variables, and the clinical or electrophysiological data. CONCLUSIONS: One
      additional patient was seen with shorter term exposure to lead fumes with
      subacute development of colicky abdominal pain, severe limb weakness, and only
      minor sensory symptoms. Unlike the patients chronically exposed to lead, he had
      massively raised porphyrins (aminolaevulinic acid 21 mg/g creatinine,
      coproporphyrins 2102 microg/g creatinine). Patients with unusually long term
      inorganic lead exposure showed mild sensory and autonomic neuropathic features
      rather than the motor neuropathy classically attributed to lead toxicity. It is
      proposed that the traditional motor syndrome associated with subacute lead
      poisoning is more likely to be a form of lead induced porphyria rather than a
      direct neurotoxic effect of lead.

PMID- 11459893
TI  - Diagnostic investigation of patients with chronic polyneuropathy: evaluation of a
      clinical guideline.
AB  - OBJECTIVE: (1) To evaluate a clinical guideline for the diagnostic investigation
      of patients presenting with signs and symptoms (present for longer than 6 weeks)
      suggesting a chronic polyneuropathy. (2) To investigate the contribution of
      electrophysiological studies to a focused search for aetiology in these patients.
      METHODS: A chart review was carried out of a consecutive group of outpatients in
      1993-7 at a university department of neurology, with signs and symptoms
      suggesting a polyneuropathy in whom the diagnostic investigation had been carried
      out according to a recently introduced guideline. Diagnostic tests were performed
      and final diagnoses were made. RESULTS: Unnecessary investigations were carried
      out in 108 (51%) of 213 patients and too few tests in 23 (11%) of these patients.
      In 82 (48%) of the 172 patients who fulfilled the inclusion criteria
      neurophysiological tests did not contribute to the final diagnosis.
      Neurophysiological criteria for demyelination were fulfilled in only 13 (8%) of
      the 172 patients. CONCLUSION: In patients presenting with signs and symptoms of
      chronic polyneuropathy the number of tests in the diagnostic investigation can be
      considerably reduced. In patients with signs and symptoms of polyneuropathy,
      providing the clinical phenotype is typical, in the presence of diabetes
      mellitus, renal failure, HIV infection, alcoholism, or use of potentially
      neurotoxic drugs further investigations are non-contributory. The significance of
      electrophysiological studies in the investigation of patients with polyneuropathy
      is rather to separate sensorimotor neuropathies from pure sensory neuropathies
      than to distinguish between demyelinating and axonal neuropathies.

PMID- 11459894
TI  - Transcranial magnetic stimulation studies in the Miller Fisher syndrome: evidence
      of corticospinal tract abnormality.
AB  - OBJECTIVES: To evaluate serial central motor conduction time in the Miller Fisher
      syndrome. METHOD: Three patients with classic Miller Fisher syndrome were
      evaluated clinically. They had serial central motor conduction times measured
      with transcranial magnetic stimulation and nerve conduction studies. Motor evoked
      potentials were recorded from the first dorsal interossei and abductor hallucis
      muscles. RESULTS: All three patients showed reduction in central motor conduction
      times in tandem with gradual clinical improvement at each review. CONCLUSIONS:
      There is electrophysiological evidence of a central reversible corticospinal
      tract conduction abnormality in the Miller Fisher syndrome.

PMID- 11459895
TI  - The Lewy body.

PMID- 11459896
TI  - Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects
      of variation in stimulation parameters.
AB  - OBJECTIVE: To investigate the relation between the variation of the parameters of
      stimulation and the clinical effectiveness in parkinsonian patients treated with
      deep brain stimulation of the subthalamic nucleus (STN), to provide information
      on the electrical parameter setting and the mechanism of action of deep brain
      stimulation. METHODS: Ten patients with Parkinson's disease bilaterally implanted
      in the STN were studied. For every patient the intensity of the stimulus
      necessary to obtain the disappearance of contralateral wrist rigidity (required
      clinical effect, RCE) and the side effect threshold in 20 different conditions of
      stimulation, coupling four pulse width values (60, 120, 210, 450 micros) with
      five rate values (10, 50, 90, 130, 170 Hz) were determined. All the patients were
      tested after a 12 hour withdrawal of antiparkinsonian drugs, and the clinical
      evaluation was double blind. RESULTS: In all the patients it was impossible to
      obtain the RCE using 10 and 50 Hz stimulus rates. For all the other stimulus rate
      values, the intensity-pulse width curves (IPWCs) for the RCE and for the side
      effect threshold showed a hyperbolic trend. For every pulse width value,
      increasing the rate from 90 to 130 and to 170 Hz progressively decreased the
      intensity of the stimulus necessary to reach the RCE, but the differences were
      not significant. Within the same rate value, the progressive reduction of the
      stimulus intensity necessary to obtain the RCE, obtained with the lengthening of
      the pulse width was significant (p<0.05) only comparing 60 with 210 micros and 60
      with 450 micros. CONCLUSIONS: The findings give some useful indications for the
      electrical parameter setting in deep brain stimulation of the STN, and some
      information about the mechanism of action of deep brain stimulation.

PMID- 11459897
TI  - Can item response theory reduce patient burden when measuring health status in
      neurological disorders? Results from Rasch analysis of the SF-36 physical
      functioning scale (PF-10).
AB  - BACKGROUND: Indices of physical function may have a hierarchy of items. In cases
      where this can be demonstrated it may be possible to reduce patient burden by
      asking them to complete only those items which relate directly to their own level
      of ability. OBJECTIVES: To determine whether statistical procedures,
      operationalising what is known as item response theory (IRT), can be used to
      assess the unidimensionality of the 10 item physical functioning domain of the SF
      36 in patients with Parkinson's disease and motor neuron disease, and, secondly,
      to determine whether it would be possible to administer subsets of items to
      certain patients, on the basis of their replies to other items in the scale,
      thereby reducing patient burden. METHODS: Rasch analysis, a form of IRT
      methodology, of the 10 item physical functioning domain (PF-10) in two
      neurological patient samples was undertaken and the results compared with results
      of a Rasch analysis of data gained from a population survey (the third Oxford
      healthy lifestyles survey). RESULTS: Evidence from the analyses suggests that the
      PF-10 does not form a perfect hierarchy on a unidimensional scale. However,
      certain items seem to form a hierarchy, and responses to some of them are
      contingent on responses to the other items. CONCLUSIONS: Rasch analysis of the PF
      10 in neurological patients has indicated that certain items of the scale are
      hierarchically ordered, and consequently not all respondents would need to
      complete them all: indeed those most severely ill would be required to complete
      less items than those with only limited disabilities. The implications of this
      are discussed.

PMID- 11459898
TI  - The five item Barthel index.
AB  - OBJECTIVES: Routine data collection is now considered mandatory. Therefore, staff
      rated clinical scales that consist of multiple items should have the minimum
      number of items necessary for rigorous measurement. This study explores the
      possibility of developing a short form Barthel index, suitable for use in
      clinical trials, epidemiological studies, and audit, that satisfies criteria for
      rigorous measurement and is psychometrically equivalent to the 10 item
      instrument. METHODS: Data were analysed from 844 consecutive admissions to a
      neurological rehabilitation unit in London. Random half samples were generated.
      Short forms were developed in one sample (n=419), by selecting items with the
      best measurement properties, and tested in the other (n=418). For each of the 10
      items of the BI, item total correlations and effect sizes were computed and rank
      ordered. The best items were defined as those with the lowest cross product of
      these rank orderings. The acceptability, reliability, validity, and
      responsiveness of three short form BIs (five, four, and three item) were
      determined and compared with the 10 item BI. Agreement between scores generated
      by short forms and 10 item BI was determined using intraclass correlation
      coefficients and the method of Bland and Altman. RESULTS: The five best items in
      this sample were transfers, bathing, toilet use, stairs, and mobility. Of the
      three short forms examined, the five item BI had the best measurement properties
      and was psychometrically equivalent to the 10 item BI. Agreement between scores
      generated by the two measures for individual patients was excellent (ICC=0.90)
      but not identical (limits of agreement=1.84+/-3.84). CONCLUSIONS: The five item
      short form BI may be a suitable outcome measure for group comparison studies in
      comparable samples. Further evaluations are needed. Results demonstrate a
      fundamental difference between assessment and measurement and the importance of
      incorporating psychometric methods in the development and evaluation of health
      measures.

PMID- 11459899
TI  - Christjaan Eijkman (1858-1930).

PMID- 11459900
TI  - Homozygous deletion mutation of the parkin gene in patients with atypical
      parkinsonism.
AB  - Autosomal recessive juvenile parkinsonism (AR-JP) is characterised by homogenous
      clinical features and selective degeneration of nigral neurons. Recent progress
      in molecular genetic analyses of AR-JP has led to the identification of a novel
      ubiquitin-like protein, parkin, whose precise function still remains to be
      elucidated. Two unrelated Japanese families had levodopa unresponsive
      parkinsonism complicated with cerebellar and pyramidal tract dysfunction. Genetic
      analysis of the parkin gene and mRNA in both families disclosed identical
      mutations with large deletions extending from exons 3 to 4. These results suggest
      that the parkin protein possesses an important function not only in the
      substantia nigra but also in extranigral neurons of the CNS and that the
      phenotype of multiple system dysfunction can also be a complication in patients
      with AR-JP due to variations in sites of or changes in functions by parkin
      mutation.

PMID- 11459901
TI  - Intravenous immune globulins in patients with Guillain-Barre syndrome and
      contraindications to plasma exchange: 3 days versus 6 days.
AB  - Plasma exchange is contraindicated in 10 to 20% of patients with Guillain-Barre
      syndrome (GBS). The optimal schedule for intravenous immune globulin (IVIg)
      therapy has not yet been established in these patients. The objective was to
      compare the efficacy and safety of two IVIg treatment durations in patients with
      GBS with contraindications for plasma exchange. In this randomised, double blind,
      multicentre phase II trial conducted in seven French centres, patients with GBS
      with severe haemostasis, unstable haemodynamics, or uncontrolled sepsis were
      randomly assigned to 0.4 g/kg/day IVIg for 3 or 6 days. The primary outcome
      measure was the time needed to regain the ability to walk with assistance. Thirty
      nine patients were included from March 1994 to May 1997, 21 in the 3 day group
      and 18 in the 6 day group. Time to walking with assistance was non-significantly
      shorter in the 6 day group (84 (23-121) v 131 days (51-210), p=0.08); the
      difference was significant in ventilated patients (86 days (13-151) in the 6 day
      group v 152 days (54-332) in the 3 day group; p=0.04). The prevalence and
      severity of IVIg related adverse effects were comparable between the two groups.
      In conclusion, in patients with GBS and contraindications for plasma exchange,
      especially those who need ventilatory assistance, IVIg (0.4 g/kg/day) may be more
      beneficial when given for 6 days rather than 3 days.

PMID- 11459902
TI  - Clinical study of 222 patients with pure motor stroke.
AB  - The objective was to assess the frequency of pure motor stroke caused by
      different stroke subtypes and to compare demographic, clinical, neuroimaging, and
      outcome data of pure motor stroke with those of patients with other lacunar
      stroke as well as with those of patients with non-lacunar stroke. Data from 2000
      patients with acute stroke (n=1761) or transient ischaemic attack (n=239)
      admitted consecutively to the department of neurology of an acute care 350 bed
      teaching hospital were prospectively collected in the Sagrat Cor Hospital of
      Barcelona stroke registry over a 10 year period. For the purpose of the study 222
      (12.7%) patients with pure motor stroke were selected. The other study groups
      included 218 (12.3%) patients with other lacunar strokes and 1321 (75%) patients
      with non-lacunar stroke. In relation to stroke subtype, lacunar infarcts were
      found in 189 (85%) patients, whereas ischaemic lacunar syndromes not due to
      lacunar infarcts occurred in 23 (10.4%) patients (atherothrombotic stroke in 12,
      cardioembolic stroke in seven, infarction of undetermined origin in three, and
      infarction of unusual aetiology in one) and haemorrhagic lacunar syndromes in 10
      (4.5%). Patients with pure motor stroke showed a better outcome than patients
      with non-lacunar stroke with a significantly lower number of complications and in
      hospital mortality rate, shorter duration of hospital stay, and a higher number
      of symptom free patients at hospital discharge. After multivariate analysis,
      hypertension, diabetes, obesity, hyperlipidaemia, non-sudden stroke onset,
      internal capsule involvement, and pons topography seemed to be independent
      factors of pure motor stroke in patients with acute stroke. In conclusion, about
      one of every 10 patients with acute stroke had a pure motor stroke. Pure motor
      stroke was caused by a lacunar infarct in 85% of patients and by other stroke
      subtypes in 15%. Several clinical features are more frequent in patients with
      pure motor stroke than in patients with non-lacunar stroke.

PMID- 11459903
TI  - Cerebral lymphoma presenting as a leukoencephalopathy.
AB  - Cerebral lymphoma is infrequent in immunocompetent patients. This tumour usually
      appears on CT and MRI as a single lesion or as multiple lesions with mass effect
      and homogeneous enhancement after contrast administration. A patient is described
      with a cerebral lymphoma, confirmed by histopathological examination, who
      presented as a progressive leukoencephalopathy.

PMID- 11459904
TI  - Clinical features of transient monocular blindness and the likelihood of
      atherosclerotic lesions of the internal carotid artery.
AB  - To assess which features of transient monocular blindness (TMB) are associated
      with atherosclerotic changes in the ipsilateral internal carotid artery (ICA),
      337 patients with sudden, transient monocular loss of vision were prospectively
      studied. History characteristics of the attack were compared with the presence of
      atherosclerotic lesions of the ipsilateral ICA. All patients were directly
      interviewed by a single investigator. Of all patients, 159 had a normal ICA on
      the relevant side, 33 had a stenosis between 0%-69%, 100 had a stenosis of 70%
      99%, and 45 had an ICA occlusion. An altitudinal onset or disappearance of
      symptoms was associated with atherosclerotic lesions of the ipsilateral ICA. A
      severe (70%-99%) stenosis was also associated with a duration between 1 and 10
      minutes, and with a speed of onset in seconds. An ICA occlusion was associated
      with attacks being provoked by bright light, an altitudinal onset, and the
      occurrence of more than 10 attacks. Patients who could not remember details about
      the mode of onset, disappearance, or duration of the attack were likely to have a
      normal ICA. Our findings may facilitate the clinical decision whether or not to
      perform ancillary investigations in these patients.

PMID- 11459905
TI  - Neuronal damage in the interval form of CO poisoning determined by serial
      diffusion weighted magnetic resonance imaging plus 1H-magnetic resonance
      spectroscopy.
AB  - In a patient with the interval form of carbon monoxide (CO) poisoning diffusion
      weighted MRI and proton magnetic resonance spectroscopy (1H-MRS) were serially
      performed immediately after the appearance of delayed sequelae (the 23rd day
      after exposure). During the period in which few clear findings were evident on
      MRI T2 weighted images, a high signal area in the cerebral white matter and
      relative decrease in the apparent diffusion coefficient (ADCav) were already
      apparent on diffusion weighted images, with these findings thought to sensitively
      reflect the tissue injury associated with the onset of sequelae. The decrease in
      relative ADCav persisted until the 38th day after exposure. Subsequently, ADCav
      gradually increased, and in the cerebral white matter showed higher values in the
      118th day after exposure than immediately after the onset of sequelae. During
      this period, on 1H-MRS choline containing compounds showed persistently high
      values throughout the course, with N-acetylaspartate depletion and the appearance
      of a lactate peak later in the course. These findings, with regional specificity
      in the cerebral white matter, reflect the developmental process of the white
      matter lesions in the interval form of CO poisoning in which demyelination
      progresses leading to neuronal necrosis. Serial diffusion weighted imaging plus
      1H-MRS measurements are useful in determining the tissue damage and long term
      outcome of delayed sequelae associated with the interval form of CO poisoning.

PMID- 11459906
TI  - Selective impairment of facial recognition due to a haematoma restricted to the
      right fusiform and lateral occipital region.
AB  - A 67 year old right handed Japanese man developed prosopagnosia caused by a
      haemorrhage. His only deficit was the inability to perceive and discriminate
      unfamiliar faces, and to recognise familiar faces. He did not show deficits in
      visual or visuospatial perception of non-facial stimuli, alexia, visual agnosia,
      or topographical disorientation. Brain MRI showed a haematoma limited to the
      right fusiform and the lateral occipital region. Single photon emission computed
      tomography confirmed that there was no decreased blood flow in the opposite left
      cerebral hemisphere. The present case indicates that a well placed small right
      fusiform gyrus and the adjacent area can cause isolated impairment of facial
      recognition. As far as we know, there has been no published case that has
      demonstrated this exact lesion site, which was indicated by recent functional MRI
      studies as the most critical area in facial recognition.

PMID- 11459907
TI  - Relation between depression after stroke, antidepressant therapy, and functional
      recovery.
AB  - The aim was to evaluate the effects of poststroke depression and antidepressant
      therapy on the improvement of motor scores and disability, to verify if the
      negative effects of poststroke depression on functional recovery could be
      counterbalanced by taking antidepressant drugs. RESULTS OBTAINED BEFORE, DURING,
      AND AFTER REHABILITATION: On the Barthel index, Canadian neurological scale, and
      Rivermead mobility index-by 49 depressed patients with stroke, who had been
      treated (n=25) or not treated (n=24) according to the different therapeutic
      approaches of their physicians, were compared with results similarly obtained by
      15 non-depressed patients with stroke. Analysis was by multivariate analysis of
      variance for repeated measures There was a non-significant difference between the
      groups in their motor and functional scores, and a significant improvement on
      time. A significant interaction between group and time was seen. This interaction
      was particularly significant on the Rivermead mobility index, and was due to the
      fact that the recovery of non-treated depressed patients with stroke was less
      than the non-depressed and the depressed but treated patients with stroke.
      Furthermore, recovery from depression was significantly greater in treated than
      in non-treated depressed patients with stroke. In conclusion, poststroke
      depression has negative effects on functional recovery, and a pharmacological
      treatment of depression can counterbalance this effect.

PMID- 11459908
TI  - Cervical dystonia is associated with a polymorphism in the dopamine (D5) receptor
      gene.
AB  - The objective was to assess whether polymorphisms in the dopamine receptor and
      transporter genes are associated with development of primary cervical dystonia. A
      case-control allelic association study is described of 100 patients with cervical
      dystonia and 100 controls using polymorphisms within D1-5 receptor and dopamine
      transporter genes. No significant association was found between patient and
      control allele frequencies for polymorphisms in genes for the D1 to 4 receptors
      and dopamine transporter. Significant associations, however, were found for
      alleles 2 and 6 of the D5 receptor microsatellite. Carriage of allele 2 was
      associated with cervical dystonia, whereas allele 6 was overrepresented in the
      control group, implying a possible protective effect. The association with allele
      6 remained significant after Bonferroni correction. In conclusion, the finding of
      a significant association with an allele in the D5 receptor gene in patients with
      cervical dystonia may indicate a pathogenic role of this gene (or neighbouring
      genes). Further studies are required to confirm this finding and to assess
      whether these alleles are part of distinct haplotypes associated with other
      polymorphisms imparting a functional effect on the D5 receptor.

PMID- 11459909
TI  - Motor neuron disease after electric injury.
AB  - The occurrence of motor neuron disease after electrical injury in six patients is
      reported and compared with patients from the literature. The patients were five
      men with spinal onset and one woman with bulbar motor neuron disease after
      electric shock. Two patients were struck by lightning and four by industrial
      electric shock. For all six of them, the disease started at the site of the
      electrical trauma. The mean delay for onset of motor neuron disease was 44
      months. In four of the spinal patients the disease progressed slowly with mild
      handicap after several years. For the fifth patient, improvement was noted
      progressively. The patient with bulbar disease died 26 months after onset. A link
      between electric shock and motor neuron disease is likely, given the homogenous
      profile of the patients both in the five spinal cases presented here and in the
      literature. Bulbar onset has not been reported to date. However, in this patient
      the long delay between the electrical injury and motor neuron disease, together
      with the rapid evolution may suggest a chance association.

PMID- 11459910
TI  - Neuropsychological and psychiatric complications in endoscopic third
      ventriculostomy: a clinical case report.
AB  - The clinical case report of a patient who underwent an endoscopic third
      ventriculostomy for the treatment of a slit ventricle syndrome is presented.
      After surgery the patient developed a severe complication consisting of an
      organic personality disorder, characterised by impulsiveness, physical
      heteroaggressiveness, binge eating, hypersomnia and impairment of memory, and
      frontal-executive functions.A frontal lobe lesion may explain some of the
      symptoms presented, such as the uncontrolled impulses, the aggressive behaviour,
      and even the binge eating. However, a longitudinal neuropsychological evaluation
      showed a severe deficit in immediate memory and difficulties in planning and
      consolidation of newly learned information, which may be best related to damage
      in the frontal basal structures of the brain: the fornix and its connection to
      the hippocampus and the mamillary bodies. Postoperative MR images confirmed the
      clinical hypothesis. The emergence of such a severe organic personality disorder
      and cognitive disturbances as a psychiatric complication of an endoscopic third
      ventriculostomy has not, it seems, been previously reported elsewhere. Clinicians
      should take these possible complications into account when recommending this so
      called minimally invasive neuroendoscopic procedure.

PMID- 11459911
TI  - Efficacy of high dose steroid therapy in children with severe acute transverse
      myelitis.
AB  - No effective treatment has been demonstrated for patients with acute transverse
      myelopathy. In a multicentre controlled study, 12 children with severe acute
      transverse myelopathy were treated with intravenous methylprednisolone (IVMP) and
      compared with a historical group of 17 patients. The treatment had a significant
      effect on the proportion of patients walking independently at 1 month and on the
      proportion with full recovery at 1 year, with no differences in the frequency of
      complications between the two groups.

PMID- 11459912
TI  - Bilateral substantia nigra lesions on magnetic resonance imaging in a patient
      with encephalitis lethargica.

PMID- 11459913
TI  - Vertigo and amaurosis fugax secondary to Takayasu's arteritis.

PMID- 11459916
TI  - 'I know your name but not your face': explaining modality-based differences in
      access to biographical knowledge in a patient with retrograde amnesia.
AB  - In current functional models of person recognition it is proposed that there
      exists a single common body of semantic information concerning people accessible
      from all modalities (e.g. names, faces). In this paper, we present evidence that
      challenges this view. Two experiments are discussed investigating residual
      autobiographical and public knowledge in a patient suffering from retrograde
      amnesia. Knowledge about people was investigated in each case by asking a series
      of questions, ranging from the very general to the very specific. Experiment 1
      examined knowledge about famous people. The results showed that the patient
      accessed more information about famous people when cued with names than when cued
      with faces. Experiment 2 examined knowledge about people known personally to the
      patient. Again, the same pattern of results emerged. While the patient responded
      accurately to all questions posed with name cues, her ability to recall the same
      information when prompted with face cues was clearly inferior. This modality
      based difference in accessing biographical knowledge is discussed in relation to
      models of person recognition.

PMID- 11459917
TI  - When living things and other 'sensory quality' categories behave in the same
      fashion: a novel category specificity effect.
AB  - In this study, the performance on semantic tests of five patients with a
      diagnosis of probable herpes simplex encephalitis was examined. Only one of the
      patients, MU, showed a marked category-specific deficit for living things, unlike
      the other patients. Results which closely mirrored those obtained with the
      category living things were found in each of the five patients for the other
      categories, edible substances, materials, and liquids, selected for a priori
      theoretical reasons. The processing of these additional categories was
      investigated with tasks involving naming abilities in different modalities,
      matching to sample, and questionnaires exploring the status of the patients'
      knowledge about the semantic features of both living things and exemplars of
      novel 'sensory quality' categories. MU showed in all tasks a comparable
      impairment for both living things and the other three new categories, in spite of
      a performance closely equivalent to that of the other four patients with man-made
      artefacts. This finding supports an explanation of MU's performance in terms of
      an impairment relating to categories highly dependent on the sensory quality of
      stimuli. In addition, his difficulty involved all aspects of the processing of
      the impaired categories.

PMID- 11459918
TI  - Word-centred neglect dyslexia: evidence from a new case.
AB  - Neglect dyslexia resulting from damage to word-centred representations is
      extremely rare. We report on a new case. A left-handed subject, SVE, presented
      with aphasia and neglect dyslexia/dysgraphia following a right hemisphere stroke.
      In tachistoscopic reading tasks, some of his errors resulted from retina-centred
      neglect, as he responded more accurately to words flashed in the left visual
      field than to words flashed in the right visual field. However, the critical
      aspects of his reading performance indicated word-centred neglect. SVE
      incorrectly produced the initial elements of four-letter words, regardless of
      stimulus location (to the left and to the right of fixation, or at fixation), and
      orientation (horizontal and vertical presentation). A similar distribution of
      errors was demonstrated in writing (very inaccurate performance on initial
      letters). This pattern of performance suggests damage to an abstract letter
      string representation defined by spatial coordinates, rather than to an ordering
      mechanism. It is most naturally accommodated by models of word recognition which
      assume a word-centred level of representation, and cannot be explained by models
      which do not include such a representational level. Consideration of our subject
      in the light of other similar reports prompts hypotheses on the neural mechanisms
      involved in computing word-centred representations.

PMID- 11459919
TI  - Mirrored-self misidentification: two cases of focal onset dementia.
AB  - We present two patients in whom the mirror sign, the inability to recognize one's
      own reflected image, was a stable and persisting symptom signalling the onset of
      a progressive dementing illness. Extensive neuropsychological testing was
      conducted with both patients, with particular emphasis on face processing and the
      understanding of reflected space. Both patients were also investigated with
      structural imaging techniques (computed tomography and magnetic resonance
      imaging). Although the neuroimaging results were not strongly lateralizing for
      either patient, neuropsychological testing revealed striking right hemisphere
      dysfunction with relatively intact left hemisphere cognitive function in both
      patients. Of particular interest was the patients' dissociation on tests of face
      processing; one patient, FE, had significant face processing deficits while the
      other patient, TH, had relatively intact face processing. Further testing with TH
      revealed striking deficits in his ability to interpret reflected space. The
      results of the face processing tests are discussed in the context of current
      models of normal face processing, with particular emphasis on the affective
      component in face recognition. We propose that a combination of cognitive
      deficits underlie the mirror sign delusion, including perceptual, affective and
      reasoning impairments, and also discuss the contributions of cortical and
      subcortical lesions in these two patients and in delusions in general.

PMID- 11459920
TI  - Different brain areas activated during imagery of painful and non-painful 'finger
      movements' in a subject with an amputated arm.
AB  - The purpose of the present study was to investigate differences in brain
      activation with functional magnetic resonance imaging (fMRI) during imagery of
      painful and non-painful 'finger movements' and 'hand positioning' in a subject
      with an amputated arm. The subject was a right-handed man in his mid-thirties who
      lost his right arm just above the elbow in a car-train accident. MRI was
      performed with a 1.5 T Siemens Vision Plus scanner. The basic design involved
      four conditions: imagining 'painful finger movements', 'non-painful finger
      movements', 'painful hand positioning', 'non-painful hand positioning'. Imagery
      of finger movements uniquely activated the contralateral primary motor cortex
      which contains the classic 'hand area'. The lateral part of the anterior
      cerebellar lobe was also activated during imagery of finger movements. Imagery of
      pain uniquely activated the somatosensory area, and areas in the left insula and
      bilaterally in the ventral posterior lateral nucleus of the thalamus. It is
      suggested that the insula and thalamus may involve neuronal pathways that are
      critical for mental processing of pain-related experiences, which may relate to a
      better understanding of the neurobiology of phantom limb pain.

PMID- 11459921
TI  - A neuropsychological-neuropathological case study of variant Creutzfeldt-Jakob
      disease.
AB  - We report the first neuropsychological-neuropathological case study of a patient
      with variant Creutzfeldt-Jakob disease (vCJD) who was seen at the early stages of
      the disease, and whose cognitive functioning was monitored in the following
      months until his death. At presentation, his neuropsychological profile included
      impaired ability to retain new episodic information, deficits on tests of
      retrieval from semantic memory, and impairments on tests of memory for public
      knowledge, such as famous personalities. Tests of executive function were also
      performed poorly. Picture recognition memory and autobiographical memory were
      relatively spared, as was performance on tests of face perception and complex
      copying ability. Neuropsychological testing may be useful in monitoring the
      progression of vCJD, and we provide evidence to show a steady rate of decline in
      perceptual and naming tasks over a 4-month period. Post-mortem findings showed
      neuronal loss in the caudate, putamen, dorsal thalamus, cerebellum and occipital
      cortex. Spongiform changes were found throughout the brain, including the
      entorhinal cortex and anterior thalamus. Prion protein accumulation was noted in
      the hippocampus. We hypothesize that primary subcortical damage to structures in
      the thalamus and neostriatum, together with secondary frontal lobe dysfunction,
      combine to yield the pattern of neuropsychological impairment and
      neuropsychological sparing that was found.

PMID- 11459922
TI  - Full-length cDNAs: more than just reaching the ends.
AB  - The development of functional genomic resources is essential to understand and
      utilize information generated from genome sequencing projects. Central to the
      development of this technology is the creation of high-quality cDNA resources and
      improved technologies for analyzing coding and noncoding mRNA sequences. The
      isolation and mapping of cDNAs is an entree to characterizing the information
      that is of significant biological relevance in the genome of an organism.
      However, a bottleneck is often encountered when attempting to bring to full
      length (or at least full-coding) a number of incomplete cDNAs in parallel, since
      this involves the nonsystematic, time consuming, and labor-intensive iterative
      screening of a number of cDNA libraries of variable quality and/or directed
      strategies to process individual clones (e.g., 5' rapid amplification of cDNA
      ends). Here, we review the current state of the art in cDNA library generation,
      as well as present an analysis of the different steps involved in cDNA library
      generation.

PMID- 11459923
TI  - KGF alters gene expression in human airway epithelia: potential regulation of the
      inflammatory response.
AB  - Keratinocyte growth factor (KGF) regulates several functions in adult and
      developing lung epithelia; it causes proliferation, stimulates secretion of fluid
      and electrolytes, enhances repair, and may minimize injury. To gain insight into
      the molecular processes influenced by KGF, we applied KGF to primary cultures of
      well-differentiated human airway epithelia and used microarray hybridization to
      assess the abundance of gene transcripts. Of 7,069 genes tested, KGF changed
      expression levels of 910. Earlier studies showed that KGF causes epithelial
      proliferation, and as expected, treatment altered expression of numerous genes
      involved in cell proliferation. We found that KGF stimulated transepithelial Cl(
      ) transport, but the number of cystic fibrosis (CF) transmembrane conductance
      regulator (CFTR) transcripts fell. Although transcripts for ClC-1 and ClC-7 Cl(-)
      channels increased, KGF failed to augment transepithelial Cl(-) transport in CF
      epithelia, suggesting that KGF-stimulated Cl(-) transport in differentiated
      airway epithelia depends on the CFTR Cl(-) channel. Interestingly, KGF decreased
      transcripts for many interferon (IFN)-induced genes. IFN causes trafficking of
      Stat dimers to the nucleus, where they activate transcription of IFN-induced
      genes. We found that KGF prevented the IFN-stimulated trafficking of Stat1 from
      the cytosol to the nucleus, suggesting a molecular mechanism for KGF-mediated
      suppression of the IFN-signaling pathway. These results suggest that in addition
      to stimulating proliferation and repair of damaged airway epithelia, KGF
      stimulates Cl(-) transport and may dampen the response of epithelial cells to
      inflammatory mediators.

PMID- 11459924
TI  - Rat mitochondrial ATP synthase ATP5G3: cloning and upregulation in pancreas after
      chronic ethanol feeding.
AB  - Individuals with chronic excessive alcohol ingestion are put at the risk of acute
      and chronic pancreatitis. Underlying molecular mechanisms are unknown.
      Differential gene expression in the pancreas was profiled using mRNA differential
      display by comparison between control and ethanol-consuming rats. Male Wistar
      rats were fed with diets containing 6.7% (vol/vol) ethanol for 4 wk. A cDNA tag
      that was overexpressed in the pancreas of rats fed ethanol was isolated. A 723-bp
      cDNA was cloned from a rat pancreatic cDNA library, which encodes a novel rat
      mitochondrial ATP synthase subunit 9, isoform 3 (ATP5G3), which is homologous to
      a human ATP5G3 gene. Real-time PCR demonstrated that all three nuclear gene
      isoforms (ATP5G1, ATP5G2, and ATP5G3) were consistently upregulated in the
      pancreas of alcohol-consuming rats, parallel with mitochondrial injury. The
      cellular response to mitochondrial damage and metabolic stress may reflect an
      adaptive process for mitochondrial repair in pancreatic acinar cells during
      chronic ethanol ingestion.

PMID- 11459925
TI  - Altered Na+-K+ pump activity and plasma lipids in salt-hypertensive Dahl rats:
      relationship to Atp1a1 gene.
AB  - A genetic variant of the gene for the alpha(1)-isoform of Na(+)-K(+)-ATPase
      (Atp1a1) was suggested to be involved in the pathogenesis of salt hypertension in
      Dahl rats through altered Na(+):K(+) coupling ratio. We studied Na(+)-K(+) pump
      activity in erythrocytes of Dahl salt-sensitive (SS/Jr) rats in relation to
      plasma lipids and blood pressure (BP) and the linkage of polymorphic
      microsatellite marker D2Arb18 (located within intron 1 and exon 2 of Atp1a1 gene)
      with various phenotypes in 130 SS/Jr x SR/Jr F(2) rats. Salt-hypertensive SS/Jr
      rats had higher erythrocyte Na(+) content, enhanced ouabain-sensitive (OS) Na(+)
      and Rb(+) transport, and higher Na(+):Rb(+) coupling ratio of the Na(+)-K(+)
      pump. BP of F(2) hybrids correlated with erythrocyte Na(+) content, OS Na(+)
      extrusion, and OS Na(+):Rb(+) coupling ratio, but not with OS Rb(+) uptake. In
      F(2) hybrids there was a significant association indicating suggestive linkage (P
      < 0.005, LOD score 2.5) of an intragenic marker D2Arb18 with pulse pressure but
      not with mean arterial pressure or any parameter of Na(+)-K(+) pump activity
      (including its Na(+):Rb(+) coupling ratio). In contrast, plasma cholesterol,
      which was elevated in salt-hypertensive Dahl rats and which correlated with BP in
      F(2) hybrids, was also positively associated with OS Na(+) extrusion. The
      abnormal Na(+):K(+) stoichiometry of the Na(+)-K(+) pump is a consequence of
      elevated erythrocyte Na(+) content and suppressed OS Rb(+):K(+) exchange. In
      conclusion, abnormal cholesterol metabolism but not the Atp1a1 gene locus might
      represent an important factor for both high BP and altered Na(+)-K(+) pump
      function in salt-hypertensive Dahl rats.

PMID- 11459926
TI  - Microarray analysis of trophoblast differentiation: gene expression reprogramming
      in key gene function categories.
AB  - Placental development results from a highly dynamic differentiation program. We
      used DNA microarray analysis to characterize the process by which human
      cytotrophoblast cells differentiate into syncytiotrophoblast cells in a purified
      cell culture system. Of 6,918 genes analyzed, 141 genes were induced and 256 were
      downregulated by more than 2-fold. Dynamically regulated genes were divided by
      the K-means algorithm into 9 kinetic pattern groups, then by biologic
      classification into 6 overall functional categories: cell and tissue structural
      dynamics, cell cycle and apoptosis, intercellular communication, metabolism,
      regulation of gene expression, and expressed sequence tag (EST) and function
      unknown. Gene expression changes within key functional categories were tightly
      coupled to morphological changes. In several key gene function categories, such
      as cell and tissue structure, many gene members of the category were strongly
      activated while others were strongly repressed. These findings suggest that
      differentiation is augmented by "categorical reprogramming" in which the function
      of induced genes is enhanced by preventing the further synthesis of categorically
      related gene products.

PMID- 11459927
TI  - Changes in the mitochondrial proteome from mouse hearts deficient in creatine
      kinase.
AB  - Creatine kinase (CK) is an abundant enzyme, important for maintenance of high
      energy phosphate homeostasis in many tissues including heart. Double-knockout CK
      (DbKO-CK) mice missing both the muscle (MM) and sarcomeric mitochondrial (ScMit)
      isoforms of CK have recently been studied. Despite a large change in skeletal
      muscle function in DbKO-CK mice, there is little functional change in the heart.
      To investigate whether there are specific changes in cardiac mitochondrial
      proteins associated with the loss of MM- and ScMit-CK isoforms, we have used
      difference gel electrophoresis (DIGE) to compare mitochondrial proteins from wild
      type and DbKO-CK mice. Mass spectrometry fingerprinting was used to identify 40
      spots as known mitochondrial proteins. We have discovered that the loss of MM-
      and ScMit-CK isoforms did not cause large scale changes in heart mitochondrial
      proteins. The loss of ScMit-CK was readily detected in the DbKO-CK samples. We
      have also detected a large decrease in the precursor form of aconitase.
      Furthermore, two mitochondrial protein differences have been found in the parent
      mouse strains of the DbKO-CK mice.

PMID- 11459928
TI  - Identification of a chloride-formate exchanger expressed on the brush border
      membrane of renal proximal tubule cells.
AB  - A key function of the proximal tubule is retrieval of most of the vast quantities
      of NaCl and water filtered by the kidney. Physiological studies using brush
      border vesicles and perfused tubules have indicated that a major fraction of Cl(
      ) reabsorption across the apical membrane of proximal tubule cells occurs via Cl(
      )-formate exchange. The molecular identity of the transporter responsible for
      renal brush border Cl(-)-formate exchange has yet to be elucidated. As a strategy
      to identify one or more anion exchangers responsible for mediating Cl(-)
      reabsorption in the proximal tubule, we screened the expressed sequence tag
      database for homologs of pendrin, a transporter previously shown to mediate Cl(-)
      formate exchange. We now report the cDNA cloning of CFEX, a mouse pendrin homolog
      with expression in the kidney by Northern analysis. Sequence analysis indicated
      that CFEX very likely represents the mouse ortholog of human SLC26A6.
      Immunolocalization studies detected expression of CFEX, but not pendrin, on the
      brush border membrane of proximal tubule cells. Functional expression studies in
      Xenopus oocytes demonstrated that CFEX mediates Cl(-)-formate exchange. Taken
      together, these observations identify CFEX as a prime candidate to mediate Cl(-)
      formate exchange in the proximal tubule and thereby to contribute importantly to
      renal NaCl reabsorption. Given its wide tissue distribution, CFEX also may
      contribute to transcellular Cl(-) transport in additional epithelia such as the
      pancreas and contribute to transmembrane Cl(-) transport in nonepithelial tissues
      such as the heart.

PMID- 11459929
TI  - Trace amines: identification of a family of mammalian G protein-coupled
      receptors.
AB  - Tyramine, beta-phenylethylamine, tryptamine, and octopamine are biogenic amines
      present in trace levels in mammalian nervous systems. Although some "trace
      amines" have clearly defined roles as neurotransmitters in invertebrates, the
      extent to which they function as true neurotransmitters in vertebrates has
      remained speculative. Using a degenerate PCR approach, we have identified 15 G
      protein-coupled receptors (GPCR) from human and rodent tissues. Together with the
      orphan receptor PNR, these receptors form a subfamily of rhodopsin GPCRs distinct
      from, but related to the classical biogenic amine receptors. We have demonstrated
      that two of these receptors bind and/or are activated by trace amines. The
      cloning of mammalian GPCRs for trace amines supports a role for trace amines as
      neurotransmitters in vertebrates. Three of the four human receptors from this
      family are present in the amygdala, possibly linking trace amine receptors to
      affective disorders. The identification of this family of receptors should
      rekindle the investigation of the roles of trace amines in mammalian nervous
      systems and may potentially lead to the development of novel therapeutics for a
      variety of indications.

PMID- 11459930
TI  - Carbohydrate self-recognition mediates marine sponge cellular adhesion.
AB  - Sponges (Porifera), the simplest and earliest multicellular organisms, are
      thought to have evolved from their unicellular ancestors about 1 billion years
      ago by developing cell-recognition and adhesion mechanisms to discriminate
      against "non-self." Consequently, they are used as models for investigating
      recognition phenomena. Cellular adhesion of marine sponges is an event involving
      adherence of extracellular proteoglycan-like molecules, otherwise known as
      aggregation factors (AFs). In a calcium-independent process the AFs adhere to the
      cell surface, and in a calcium-dependent process they exhibit AF self
      association. A mechanism which has been implied but not definitely proven to play
      a role in the calcium-dependent event is self-recognition of defined carbohydrate
      epitopes. For the red beard sponge, Microciona prolifera, two carbohydrate
      epitopes, a sulfated disaccharide and a pyruvylated trisaccharide, have been
      implicated in cellular adhesion. To investigate this phenomenon a system has been
      designed, by using surface plasmon resonance detection, to mimic the role of
      carbohydrates in cellular adhesion of M. prolifera. The results show self
      recognition of the sulfated disaccharide to be a major force behind the calcium
      dependent event. The interaction is not simply based on electrostatic
      interactions, as other sulfated carbohydrates analyzed by using this procedure
      did not self-associate. Furthermore, the interaction is completely eradicated on
      substitution of Ca(2+) ions by either Mg(2+) or Mn(2+) ions. This physiologically
      relevant recognition mechanism confirms the existence of true carbohydrate self
      recognition, and may have significant implications for the role of carbohydrates
      in cellular recognition of higher organisms.

PMID- 11459931
TI  - Transient decrease in water diffusion observed in human occipital cortex during
      visual stimulation.
AB  - Using MRI, we report the observation of a transient decrease of the apparent
      diffusion coefficient (ADC) of water in the human brain visual cortex during
      activation by a black and white 8-Hz-flickering checkerboard. The ADC decrease
      was small (<1%), but significant and reproducible, and closely followed the time
      course of the activation paradigm. Based on the known sensitivity of diffusion
      MRI to cell size in tissues and on optical imaging studies that have revealed
      changes in the shape of neurons and glial cells during activation, the observed
      ADC findings have been tentatively ascribed to a transient swelling of cortical
      cells. These preliminary results suggest a new approach to produce images of
      brain activation with MRI from signals directly associated with neuronal
      activation, and not through changes in local blood flow.

PMID- 11459932
TI  - Angiogenic role for glycodelin in tumorigenesis.
AB  - Angiogenesis plays an important role in neovascularization in tumors. Glycodelin,
      a hormone-responsive protein, has been detected in tumors of reproductive organs
      and is found in high levels in the plasma of subjects with gynecological
      malignancies. Glycodelin is also found in the endothelial cells of the umbilical
      cord and in the blood vessels of tumors. In this study, we tested whether
      glycodelin-rich amniotic fluid and a synthetic peptide derived from the sequence
      of glycodelin peptide (Gp) might promote angiogenic response by examining the
      migration and tube formation in human umbilical cord vein endothelial cells
      (HUVECs). Increased migration and tube formation of HUVECs were found in the
      presence of amniotic fluid and Gp, and this increase was blocked by antibody to
      Gp and by an anti-vascular endothelial growth factor (VEGF) antibody, suggesting
      that the angiogenic effects of glycodelin might be mediated by VEGF. The results
      also showed that Gp significantly increased the release of VEGF protein and mRNA
      expression in HUVECs, RL-95 (human endometrial carcinoma cells), OVCAR-3 (human
      ovarian adenocarcinoma cells), EM42 (human endometrial epithelial cells), THP-1
      (human monocyte), and MCF-7 and MDA-MB-231 (human breast adenocarcinoma cells)
      cell lines. VEGF receptor Fit-1 mRNA expression in HUVECs was also increased in
      the presence of Gp. These findings, together with the suggestion from the
      literature that glycodelin may have immunosuppressive properties, suggest that
      glycodelin might play an important role in neovascularization during
      embryogenesis and tumor development.

PMID- 11459933
TI  - Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral
      infection.
AB  - Normal levels of CD4(+) regulatory T cells are critical for the maintenance of
      immunological homeostasis and the prevention of autoimmune diseases. However, we
      now show that the expansion of CD4(+) regulatory T cells in response to a chronic
      viral infection can lead to immunosuppression. Mice persistently infected with
      Friend retrovirus develop approximately twice the normal percentage of splenic
      CD4(+) regulatory T cells and lose their ability to reject certain tumor
      transplants. The role of CD4(+) regulatory T cells was demonstrated by the
      transmission of immunosuppression to uninfected mice by adoptive transfers of
      CD4(+) T cells. CD4(+) T cells from chronically infected mice were also
      immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes
      in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell
      formation through a mechanism or mechanisms involving transforming growth factor
      beta and the cell surface molecule CTLA-4 (CD152). These results suggest a
      possible explanation for HIV- and human T cell leukemia virus-I-induced
      immunosuppression in the absence of T cell depletion.

PMID- 11459934
TI  - Holins kill without warning.
AB  - Holins comprise the most diverse functional group of proteins known. They are
      small bacteriophage-encoded proteins that accumulate during the period of late
      protein synthesis after infection and cause lysis of the host cell at a precise
      genetically programmed time. It is unknown how holins achieve temporal precision,
      but a conserved feature of their function is that energy poisons subvert the
      normal scheduling mechanism and instantly trigger membrane disruption. On this
      basis, timing has been proposed to involve a progressive decrease in the
      energized state of the membrane until a critical triggering level is reached.
      Here, we report that membrane integrity is not compromised after the induction of
      holin synthesis until seconds before lysis. The proton motive force was monitored
      by the rotation of individual cells tethered by a single flagellum. The results
      suggest an alternative explanation for the lysis "clock," in which holin
      concentrations build to a critical level that leads to formation of an oligomeric
      complex that disrupts the membrane.

PMID- 11459935
TI  - Regulation of myostatin activity and muscle growth.
AB  - Myostatin is a transforming growth factor-beta family member that acts as a
      negative regulator of skeletal muscle mass. To identify possible myostatin
      inhibitors that may have applications for promoting muscle growth, we
      investigated the regulation of myostatin signaling. Myostatin protein purified
      from mammalian cells consisted of a noncovalently held complex of the N-terminal
      propeptide and a disulfide-linked dimer of C-terminal fragments. The purified C
      terminal myostatin dimer was capable of binding the activin type II receptors,
      Act RIIB and, to a lesser extent, Act RIIA. Binding of myostatin to Act RIIB
      could be inhibited by the activin-binding protein follistatin and, at higher
      concentrations, by the myostatin propeptide. To determine the functional
      significance of these interactions in vivo, we generated transgenic mice
      expressing high levels of the propeptide, follistatin, or a dominant-negative
      form of Act RIIB by using a skeletal muscle-specific promoter. Independent
      transgenic mouse lines for each construct exhibited dramatic increases in muscle
      mass comparable to those seen in myostatin knockout mice. Our findings suggest
      that the propeptide, follistatin, or other molecules that block signaling through
      this pathway may be useful agents for enhancing muscle growth for both human
      therapeutic and agricultural applications.

PMID- 11459936
TI  - Eavesdropping and animal conflict.
AB  - Fights between pairs of animals frequently take place within a wider social
      context. The displays exchanged during conflict, and the outcome of an encounter,
      are often detectable by individuals who are not immediately involved. In at least
      some species, such bystanders are known to eavesdrop on contests between others,
      and to modify their behavior toward the contestants in response to the observed
      interaction. Here, I extend Maynard Smith's well known model of animal
      aggression, the Hawk-Dove game, to incorporate the possibility of eavesdroppers.
      I show that some eavesdropping is favored whenever the cost of losing an
      escalated fight exceeds the value of the contested resource, and that its
      equilibrium frequency is greatest when costs are relatively high. Eavesdropping
      reduces the risk of escalated conflict relative to that expected by chance, given
      the level of aggression in the population. However, it also promotes increased
      aggression, because it enhances the value of victory. The net result is that
      escalated conflicts are predicted to occur more frequently when eavesdropping is
      possible.

PMID- 11459937
TI  - Strong antiapostatic selection against novel rare aposematic prey.
AB  - The evolution of aposematism, a phenomenon where prey species conspicuously
      advertise their unprofitability to predators, is puzzling. How did
      conspicuousness evolve, if it simultaneously increased the likelihood of an
      inexperienced predator to detect the prey and presumably kill it? Antiapostatic
      selection, where rare prey is predated relatively more often, is considered as
      another major difficulty for aposematism to evolve. However, the risk of being
      conspicuous in low frequencies has not been experimentally tested. We designed an
      experiment to test how frequency (4%, 12%, 32%) of conspicuous aposematic prey
      and its dispersion type (solitary vs. aggregated) affect an initial predation
      risk of the prey and in avoidance learning of predators. Wild great tits (Parus
      major) were predators on artificial prey in a "novel world." The relative
      mortality of aposematic prey was antiapostatic, thus the frequency-dependent
      predation was most severe at low frequencies. In all frequencies, aggregated
      aposematic prey survived better than solitary prey. Surprisingly, learning was
      not determined by a fixed number of unpalatable prey eaten, but at low
      frequencies fewer aposematic individuals eaten generated predators' avoidance
      learning. However, per-capita risk for the prey remained highest at low
      frequencies. Our results underscore the problems of initial evolution of rare
      conspicuous morphs. Aggregated prey suffered less from predation, indicating
      selective advantage of aggregation over solitary living for a conspicuous
      individual.

PMID- 11459938
TI  - Assembling filamentous phage occlude pIV channels.
AB  - Filamentous phage f1 is exported from its Escherichia coli host without killing
      the bacterial cell. Phage-encoded protein pIV, which is required for phage
      assembly and secretion, forms large highly conductive channels in the outer
      membrane of E. coli. It has been proposed that the phage are extruded across the
      bacterial outer membrane through pIV channels. To test this prediction, we
      developed an in vivo assay by using a mutant pIV that functions in phage export
      but whose channel opens in the absence of phage extrusion. In E. coli lacking its
      native maltooligosacharride transporter LamB, this pIV variant allowed
      oligosaccharide transport across the outer membrane. This entry of
      oligosaccharide was decreased by phage production and still further decreased by
      production of phage that cannot be released from the cell surface. Thus, exiting
      phage block the pIV-dependent entry of oligosaccharide, suggesting that phage
      occupy the lumen of pIV channels. This study provides the first evidence, to our
      knowledge, for viral exit through a large aqueous channel.

PMID- 11459939
TI  - M cell-targeted DNA vaccination.
AB  - DNA immunization, although attractive, is poor for inducing mucosal immunity,
      thus limiting its protective value against most infectious agents. To surmount
      this shortcoming, we devised a method for mucosal transgene vaccination by using
      an M cell ligand to direct the DNA vaccine to mucosal inductive tissues and the
      respiratory epithelium. This ligand, reovirus protein final sigma1, when
      conjugated to polylysine (PL), can bind the apical surface of M cells from nasal
      associated lymphoid tissues. Intranasal immunizations with protein final sigma1
      PL-DNA complexes produced antigen-specific serum IgG and prolonged mucosal IgA,
      as well as enhanced cell-mediated immunity, made evident by elevated pulmonary
      cytotoxic T lymphocyte responses. Therefore, targeted transgene vaccination
      represents an approach for enabling DNA vaccination of the mucosa.

PMID- 11459940
TI  - "Electronic nose" detects major histocompatibility complex-dependent prerenal and
      postrenal odor components.
AB  - Mice prefer to mate with individuals expressing different MHC genes from their
      own. Volatile components presenting MHC-dependent odor types are present in urine
      and can be detected by mice, as shown by extensive behavioral studies. Similar
      odor types are suspected to influence human behavior as well. Although a recent
      report indicates that MHC expression influences the ratio of volatile compounds
      such as phenylacetic acid, so far no other means than studying the behavior of
      mice or rats has been available to assess odor types. Here, we report the ability
      of a gas sensor array (referred to as "electronic nose") to detect MHC-dependent
      odor types. The electronic nose consists of an array of chemophysical detectors,
      in our case quartz crystal microbalances and semiconducting metal-oxide sensors
      that change frequency or conductivity upon binding of very small numbers of
      individual molecules present in the gas phase of odorous fluids. The pattern of
      changes is characteristic for a particular smell. Our electronic nose
      distinguishes the urine odor types of MHC congenic mouse strains, MHC class I
      mutant mice, and HLA-A2 transgenic mice. In addition, MHC-dependent odor types
      can be detected in serum. The device also clearly differentiates between
      individual odor types of human sera from HLA homozygous individuals; however, HLA
      expression seems to have only a secondary influence. Thus, odor-type research can
      now be carried out with an objective and fast through-put system independent of
      behavioral studies.

PMID- 11459941
TI  - Conservation of the biochemical mechanisms of signal transduction among mammalian
      Notch family members.
AB  - Mouse Notch1, which plays an important role in cell fate determination in
      development, is proteolytically processed within its transmembrane domain by
      unidentified gamma-secretase-like activity that depends on presenilin. To study
      this proteolytic event, we established a cell-free Notch cleavage assay system
      using the membrane fraction of fibroblast transfectants of various Notch
      constructs with deletion of the extracellular portion (Notch DeltaE). The
      cytoplasmic portion of Notch1 DeltaE was released from the membrane upon
      incubation at 37 degrees C, which was inhibited by the specific gamma-secretase
      inhibitor, MW167, or by overexpression of dominant negative presenilin1.
      Likewise, other members of mouse Notch family were proteolytically cleaved in a
      presenilin-dependent, MW167-sensitive manner in vivo as well as in the cell-free
      Notch DeltaE cleavage assay system. All four members of the mouse Notch family
      migrated to the nucleus and activated the transcription from the promoter
      carrying the RBP-J consensus sequences after they were released from the
      membrane. These results demonstrate the conserved biochemical mechanism of signal
      transduction among mammalian Notch family members.

PMID- 11459942
TI  - PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine
      kinase.
AB  - PAS domains regulate the function of many intracellular signaling pathways in
      response to both extrinsic and intrinsic stimuli. PAS domain-regulated histidine
      kinases are common in prokaryotes and control a wide range of fundamental
      physiological processes. Similarly regulated kinases are rare in eukaryotes and
      are to date completely absent in mammals. PAS kinase (PASK) is an evolutionarily
      conserved gene product present in yeast, flies, and mammals. The amino acid
      sequence of PASK specifies two PAS domains followed by a canonical
      serine/threonine kinase domain, indicating that it might represent the first
      mammalian PAS-regulated protein kinase. We present evidence that the activity of
      PASK is regulated by two mechanisms. Autophosphorylation at two threonine
      residues located within the activation loop significantly increases catalytic
      activity. We further demonstrate that the N-terminal PAS domain is a cis
      regulator of PASK catalytic activity. When the PAS domain-containing region is
      removed, enzyme activity is significantly increased, and supplementation of the
      purified PAS-A domain in trans selectively inhibits PASK catalytic activity.
      These studies define a eukaryotic signaling pathway suitable for studies of PAS
      domains in a purified in vitro setting.

PMID- 11459943
TI  - Myosin I mutants with only 1% of wild-type actin-activated MgATPase activity
      retain essential in vivo function(s).
AB  - The single class I myosin (MYOA) of Aspergillus nidulans is essential for hyphal
      growth. It is generally assumed that the functions of all myosins depend on their
      actin-activated MgATPase activity. Here we show that MYOA mutants with no more
      than 1% of the actin-activated MgATPase activity of wild-type MYOA in vitro and
      no detectable in vitro motility activity can support fungal cell growth, albeit
      with a delay in germination time and a reduction in hyphal elongation. From these
      and other data, we conclude that the essential role(s) of myosin I in A. nidulans
      is probably structural, requiring little, if any, actin-activated MgATPase or
      motor activity, which have long been considered the defining characteristics of
      the myosin family.

PMID- 11459944
TI  - Hepcidin: a putative iron-regulatory hormone relevant to hereditary
      hemochromatosis and the anemia of chronic disease.

PMID- 11459945
TI  - Gene galaxies in the maize genome.

PMID- 11459946
TI  - Structural basis for bending tropomyosin around actin in muscle thin filaments.

PMID- 11459947
TI  - Dehydroepiandrosterone sulfate and longevity: new clues for an old friend.

PMID- 11459948
TI  - Probing the mechanism of enzymatic phosphoryl transfer with a chemical trick.

PMID- 11459951
TI  - Rescue of arrested replication forks by homologous recombination.
AB  - DNA synthesis is an accurate and very processive phenomenon; nevertheless,
      replication fork progression on chromosomes can be impeded by DNA lesions, DNA
      secondary structures, or DNA-bound proteins. Elements interfering with the
      progression of replication forks have been reported to induce rearrangements
      and/or render homologous recombination essential for viability, in all organisms
      from bacteria to human. Arrested replication forks may be the target of
      nucleases, thereby providing a substrate for double-strand break repair enzyme.
      For example in bacteria, direct fork breakage was proposed to occur at
      replication forks blocked by a bona fide replication terminator sequence, a
      specific site that arrests bacterial chromosome replication. Alternatively, an
      arrested replication fork may be transformed into a recombination substrate by
      reversal of the forked structures. In reversed forks, the last duplicated
      portions of the template strands reanneal, allowing the newly synthesized strands
      to pair. In bacteria, this reaction was proposed to occur in replication mutants,
      in which fork arrest is caused by a defect in a replication protein, and in UV
      irradiated cells. Recent studies suggest that it may also occur in eukaryote
      organisms. We will review here observations that link replication hindrance with
      DNA rearrangements and the possible underlying molecular processes.

PMID- 11459950
TI  - Historical overview: searching for replication help in all of the rec places.
AB  - For several decades, research into the mechanisms of genetic recombination
      proceeded without a complete understanding of its cellular function or its place
      in DNA metabolism. Many lines of research recently have coalesced to reveal a
      thorough integration of most aspects of DNA metabolism, including recombination.
      In bacteria, the primary function of homologous genetic recombination is the
      repair of stalled or collapsed replication forks. Recombinational DNA repair of
      replication forks is a surprisingly common process, even under normal growth
      conditions. The new results feature multiple pathways for repair and the
      involvement of many enzymatic systems. The long-recognized integration of
      replication and recombination in the DNA metabolism of bacteriophage T4 has moved
      into the spotlight with its clear mechanistic precedents. In eukaryotes, a
      similar integration of replication and recombination is seen in meiotic
      recombination as well as in the repair of replication forks and double-strand
      breaks generated by environmental abuse. Basic mechanisms for replication fork
      repair can now inform continued research into other aspects of recombination.
      This overview attempts to trace the history of the search for recombination
      function in bacteria and their bacteriophages, as well as some of the parallel
      paths taken in eukaryotic recombination research.

PMID- 11459952
TI  - Circles: the replication-recombination-chromosome segregation connection.
AB  - Crossing over by homologous recombination between monomeric circular chromosomes
      generates dimeric circular chromosomes that cannot be segregated to daughter
      cells during cell division. In Escherichia coli, homologous recombination is
      biased so that most homologous recombination events generate noncrossover
      monomeric circular chromosomes. This bias is lost in ruv mutants. A novel
      protein, RarA, which is highly conserved in eubacteria and eukaryotes and is
      related to the RuvB and the DnaX proteins, gamma and tau, may influence the
      formation of crossover recombinants. Those dimeric chromosomes that do form are
      converted to monomers by Xer site-specific recombination at the recombination
      site dif, located in the replication terminus region of the E. coli chromosome.
      The septum-located FtsK protein, which coordinates cell division with chromosome
      segregation, is required for a complete Xer recombination reaction at dif. Only
      correctly positioned dif sites present in a chromosomal dimer are able to access
      septum-located FtsK. FtsK acts by facilitating a conformational change in the Xer
      recombination Holliday junction intermediate formed by XerC recombinase. This
      change provides a substrate for XerD, which then completes the recombination
      reaction.

PMID- 11459953
TI  - Participation of recombination proteins in rescue of arrested replication forks
      in UV-irradiated Escherichia coli need not involve recombination.
AB  - Alternative reproductive cycles make use of different strategies to generate
      different reproductive products. In Escherichia coli, recA and several other rec
      genes are required for the generation of recombinant genomes during Hfr
      conjugation. During normal asexual reproduction, many of these same genes are
      needed to generate clonal products from UV-irradiated cells. However, unlike
      conjugation, this latter process also requires the function of the nucleotide
      excision repair genes. Following UV irradiation, the recovery of DNA replication
      requires uvrA and uvrC, as well as recA, recF, and recR. The rec genes appear to
      be required to protect and maintain replication forks that are arrested at DNA
      lesions, based on the extensive degradation of the nascent DNA that occurs in
      their absence. The products of the recJ and recQ genes process the blocked
      replication forks before the resumption of replication and may affect the
      fidelity of the recovery process. We discuss a model in which several rec gene
      products process replication forks arrested by DNA damage to facilitate the
      repair of the blocking DNA lesions by nucleotide excision repair, thereby
      allowing processive replication to resume with no need for strand exchanges or
      recombination. The poor survival of cellular populations that depend on
      recombinational pathways (compared with that in their excision repair proficient
      counterparts) suggests that at least some of the rec genes may be designed to
      function together with nucleotide excision repair in a common and predominant
      pathway by which cells faithfully recover replication and survive following UV
      induced DNA damage.

PMID- 11459954
TI  - Effects of mutations involving cell division, recombination, and chromosome dimer
      resolution on a priA2::kan mutant.
AB  - Recombinational repair of replication forks can occur either to a crossover (XO)
      or noncrossover (non-XO) depending on Holliday junction resolution. Once the fork
      is repaired by recombination, PriA is important for restarting these forks in
      Escherichia coli. PriA mutants are Rec(-) and UV sensitive and have poor
      viability and 10-fold elevated basal levels of SOS expression. PriA sulB mutant
      cells and their nucleoids were studied by differential interference contrast and
      fluorescence microscopy of 4',6-diamidino-2-phenylindole-stained log phase cells.
      Two populations of cells were seen. Eighty four percent appeared like wild type,
      and 16% of the cells were filamented and had poorly partitioned chromosomes (Par(
      )). To probe potential mechanisms leading to the two populations of cells,
      mutations were added to the priA sulB mutant. Mutating sulA or introducing lexA3
      decreased, but did not eliminate filamentation or defects in partitioning.
      Mutating either recA or recB virtually eliminated the Par(-) phenotype.
      Filamentation in the recB mutant decreased to 3%, but increased to 28% in the
      recA mutant. The ability to resolve and/or branch migrate Holliday junctions also
      appeared crucial in the priA mutant because removing either recG or ruvC was
      lethal. Lastly, it was tested whether the ability to resolve chromosome dimers
      caused by XOs was important in a priA mutant by mutating dif and the C-terminal
      portion of ftsK. Mutation of dif showed no change in phenotype whereas ftsK1cat
      was lethal with priA2kan. A model is proposed where the PriA-independent pathway
      of replication restart functions at forks that have been repaired to non-XOs.

PMID- 11459955
TI  - RecA protein promotes the regression of stalled replication forks in vitro.
AB  - Replication forks are halted by many types of DNA damage. At the site of a
      leading-strand DNA lesion, forks may stall and leave the lesion in a single
      strand gap. Fork regression is the first step in several proposed pathways that
      permit repair without generating a double-strand break. Using model DNA
      substrates designed to mimic one of the known structures of a fork stalled at a
      leading-strand lesion, we show here that RecA protein of Escherichia coli will
      promote a fork regression reaction in vitro. The regression process exhibits an
      absolute requirement for ATP hydrolysis and is enhanced when dATP replaces ATP.
      The reaction is not affected by the inclusion of the RecO and R proteins. We
      present this reaction as one of several potential RecA protein roles in the
      repair of stalled and/or collapsed replication forks in bacteria.

PMID- 11459956
TI  - Topological challenges to DNA replication: conformations at the fork.
AB  - The unwinding of the parental DNA duplex during replication causes a positive
      linking number difference, or superhelical strain, to build up around the
      elongating replication fork. The branching at the fork and this strain bring
      about different conformations from that of (-) supercoiled DNA that is not being
      replicated. The replicating DNA can form (+) precatenanes, in which the daughter
      DNAs are intertwined, and (+) supercoils. Topoisomerases have the essential role
      of relieving the superhelical strain by removing these structures. Stalled
      replication forks of molecules with a (+) superhelical strain have the additional
      option of regressing, forming a four-way junction at the replication fork. This
      four-way junction can be acted on by recombination enzymes to restart
      replication. Replication and chromosome folding are made easier by topological
      domain barriers, which sequester the substrates for topoisomerases into defined
      and concentrated regions. Domain barriers also allow replicated DNA to be (-)
      supercoiled. We discuss the importance of replicating DNA conformations and the
      roles of topoisomerases, focusing on recent work from our laboratory.

PMID- 11459957
TI  - Rescue of stalled replication forks by RecG: simultaneous translocation on the
      leading and lagging strand templates supports an active DNA unwinding model of
      fork reversal and Holliday junction formation.
AB  - Modification of damaged replication forks is emerging as a crucial factor for
      efficient chromosomal duplication and the avoidance of genetic instability. The
      RecG helicase of Escherichia coli, which is involved in recombination and DNA
      repair, has been postulated to act on stalled replication forks to promote
      replication restart via the formation of a four-stranded (Holliday) junction.
      Here we show that RecG can actively unwind the leading and lagging strand arms of
      model replication fork structures in vitro. Unwinding is achieved in each case by
      simultaneous interaction with and translocation along both the leading and
      lagging strand templates at a fork. Disruption of either of these interactions
      dramatically inhibits unwinding of the opposing duplex arm. Thus, RecG
      translocates simultaneously along two DNA strands, one with 5'-3' and the other
      with 3'-5' polarity. The unwinding of both nascent strands at a damaged fork, and
      their subsequent annealing to form a Holliday junction, may explain the ability
      of RecG to promote replication restart. Moreover, the preferential binding of
      partial forks lacking a leading strand suggests that RecG may have the ability to
      target stalled replication intermediates in vivo in which lagging strand
      synthesis has continued beyond the leading strand.

PMID- 11459958
TI  - Formation of Holliday junctions by regression of nascent DNA in intermediates
      containing stalled replication forks: RecG stimulates regression even when the
      DNA is negatively supercoiled.
AB  - Replication forks formed at bacterial origins often encounter template roadblocks
      in the form of DNA adducts and frozen protein-DNA complexes, leading to
      replication-fork stalling and inactivation. Subsequent correction of the
      corrupting template lesion and origin-independent assembly of a new replisome
      therefore are required for survival of the bacterium. A number of models for
      replication-fork restart under these conditions posit that nascent strand
      regression at the stalled fork generates a Holliday junction that is a substrate
      for subsequent processing by recombination and repair enzymes. We show here that
      early replication intermediates containing replication forks stalled in vitro by
      the accumulation of excess positive supercoils could be cleaved by the Holliday
      junction resolvases RusA and RuvC. Cleavage by RusA was inhibited by the presence
      of RuvA and was stimulated by RecG, confirming the presence of Holliday junctions
      in the replication intermediate and supporting the previous proposal that RecG
      could catalyze nascent strand regression at stalled replication forks.
      Furthermore, RecG promoted Holliday junction formation when replication
      intermediates in which the replisome had been inactivated were negatively
      supercoiled, suggesting that under intracellular conditions, the action of RecG,
      or helicases with similar activities, is necessary for the catalysis of nascent
      strand regression.

PMID- 11459959
TI  - Single-strand interruptions in replicating chromosomes cause double-strand
      breaks.
AB  - Replication-dependent chromosomal breakage suggests that replication forks
      occasionally run into nicks in template DNA and collapse, generating double
      strand ends. To model replication fork collapse in vivo, I constructed phage
      lambda chromosomes carrying the nicking site of M13 bacteriophage and infected
      with these substrates Escherichia coli cells, producing M13 nicking enzyme. I
      detected double-strand breaks at the nicking sites in lambda DNA purified from
      these cells. The double-strand breakage depends on (i) the presence of the
      nicking site; (ii) the production of the nicking enzyme; and (iii) replication of
      the nick-containing chromosome. Replication fork collapse at nicks in template
      DNA explains diverse phenomena, including eukaryotic cell killing by DNA
      topoisomerase inhibitors and inviability of recombination-deficient vertebrate
      cell lines.

PMID- 11459960
TI  - Handoff from recombinase to replisome: insights from transposition.
AB  - Bacteriophage Mu replicates as a transposable element, exploiting host enzymes to
      promote initiation of DNA synthesis. The phage-encoded transposase MuA, assembled
      into an oligomeric transpososome, promotes transfer of Mu ends to target DNA,
      creating a fork at each end, and then remains tightly bound to both forks. In the
      transition to DNA synthesis, the molecular chaperone ClpX acts first to weaken
      the transpososome's interaction with DNA, apparently activating its function as a
      molecular matchmaker. This activated transpososome promotes formation of a new
      nucleoprotein complex (prereplisome) by yet unidentified host factors [Mu
      replication factors (MRF alpha 2)], which displace the transpososome in an ATP
      dependent reaction. Primosome assembly proteins PriA, PriB, DnaT, and the DnaB-
      DnaC complex then promote the binding of the replicative helicase DnaB on the
      lagging strand template of the Mu fork. PriA helicase plays an important role in
      opening the DNA duplex for DnaB binding, which leads to assembly of DNA
      polymerase III holoenzyme to form the replisome. The MRF alpha 2 transition
      factors, assembled into a prereplisome, not only protect the fork from action by
      nonspecific host enzymes but also appear to aid in replisome assembly by helping
      to activate PriA's helicase activity. They consist of at least two separable
      components, one heat stable and the other heat labile. Although the MRF alpha 2
      components are apparently not encoded by currently known homologous recombination
      genes such as recA, recF, recO, and recR, they may fulfill an important function
      in assembling replisomes on arrested replication forks and products of homologous
      strand exchange.

PMID- 11459961
TI  - Break-induced replication: a review and an example in budding yeast.
AB  - Break-induced replication (BIR) is a nonreciprocal recombination-dependent
      replication process that is an effective mechanism to repair a broken chromosome.
      We review key roles played by BIR in maintaining genome integrity, including
      restarting DNA replication at broken replication forks and maintaining telomeres
      in the absence of telomerase. Previous studies suggested that gene targeting does
      not occur by simple crossings-over between ends of the linearized transforming
      fragment and the target chromosome, but involves extensive new DNA synthesis
      resembling BIR. We examined gene targeting in Saccharomyces cerevisiae where only
      one end of the transformed DNA has homology to chromosomal sequences. Linearized,
      centromere-containing plasmid DNA with the 5' end of the LEU2 gene at one end was
      transformed into a strain in which the 5' end of LEU2 was replaced by ADE1,
      preventing simple homologous gene replacement to become Leu2(+). Ade1(+) Leu2(+)
      transformants were recovered in which the entire LEU2 gene and as much as 7 kb of
      additional sequences were found on the plasmid, joined by microhomologies
      characteristic of nonhomologous end-joining (NHEJ). In other experiments, cells
      were transformed with DNA fragments lacking an ARS and homologous to only 50 bp
      of ADE2 added to the ends of a URA3 gene. Autonomously replicating circles were
      recovered, containing URA3 and as much as 8 kb of ADE2-adjacent sequences,
      including a nearby ARS, copied from chromosomal DNA. Thus, the end of a
      linearized DNA fragment can initiate new DNA synthesis by BIR in which the newly
      synthesized DNA is displaced and subsequently forms circles by NHEJ.

PMID- 11459962
TI  - Links between replication and recombination in Saccharomyces cerevisiae: a
      hypersensitive requirement for homologous recombination in the absence of Rad27
      activity.
AB  - The RAD27 gene of Saccharomyces cerevisiae encodes a 5'-3' flap exo/endonuclease,
      which plays an important role during DNA replication for Okazaki fragment
      maturation. Genetic studies have shown that RAD27 is not essential for growth,
      although rad27 Delta mutants are temperature sensitive. Moreover, they exhibit
      increased sensitivity to alkylating agents, enhanced spontaneous recombination,
      and repetitive DNA instability. The conditional lethality conferred by the rad27
      Delta mutation indicates that other nuclease(s) can compensate for the absence of
      Rad27. Indeed, biochemical and genetical analyses indicate that Okazaki fragment
      processing can be assured by other enzymatic activities or by alternative
      pathways such as homologous recombination. Here we present the results of a
      screen that makes use of a synthetic lethality assay to identify functions
      required for the survival of rad27 Delta strains. Altogether, we confirm that all
      genes of the Rad52 recombinational repair pathway are required for the survival
      of rad27 Delta strains at both permissive (23 degrees C) and semipermissive (30
      degrees C) temperatures for growth. We also find that several point mutations
      that confer weaker phenotypes in mitotic than in meiotic cells (rad50S, mre11s)
      and additional gene deletions (com1/sae2, srs2) exhibit synthetic lethality with
      rad27 Delta and that rad59 Delta exhibits synergistic effects with rad27 Delta.
      This and previous studies indicate that homologous recombination is the primary,
      but not only, pathway that functions to bypass the replication defects that arise
      in the absence of the Rad27 protein.

PMID- 11459963
TI  - Evidence that replication fork components catalyze establishment of cohesion
      between sister chromatids.
AB  - Accurate chromosome segregation requires that replicated sister chromatids are
      held together until anaphase, when their "cohesion" is dissolved, and they are
      pulled to opposite spindle poles by microtubules. Establishment of new cohesion
      between sister chromatids in the next cell cycle is coincident with replication
      fork passage. Emerging evidence suggests that this temporal coupling is not just
      a coincident timing of independent events, but rather that the establishment of
      cohesion is likely to involve the active participation of replication-related
      activities. These include PCNA, a processivity clamp for some DNA polymerases,
      Trf4/Pol final sigma (formerly Trf4/Pol kappa), a novel and essential DNA
      polymerase, and a modified Replication Factor C clamp--loader complex. Here we
      describe recent advances in how cohesion establishment is linked to replication,
      highlight important unanswered questions in this new field, and describe a
      "polymerase switch" model for how cohesion establishment is coupled to
      replication fork progression. Building the bridges between newly synthesized
      sister chromatids appears to be a fundamental but previously unrecognized
      function of the eukaryotic replication machinery.

PMID- 11459964
TI  - Rad52 forms DNA repair and recombination centers during S phase.
AB  - Maintenance of genomic integrity and stable transmission of genetic information
      depend on a number of DNA repair processes. Failure to faithfully perform these
      processes can result in genetic alterations and subsequent development of cancer
      and other genetic diseases. In the eukaryote Saccharomyces cerevisiae, homologous
      recombination is the major pathway for repairing DNA double-strand breaks. The
      key role played by Rad52 in this pathway has been attributed to its ability to
      seek out and mediate annealing of homologous DNA strands. In this study, we find
      that S. cerevisiae Rad52 fused to green fluorescent protein (GFP) is fully
      functional in DNA repair and recombination. After induction of DNA double-strand
      breaks by gamma-irradiation, meiosis, or the HO endonuclease, Rad52-GFP
      relocalizes from a diffuse nuclear distribution to distinct foci. Interestingly,
      Rad52 foci are formed almost exclusively during the S phase of mitotic cells,
      consistent with coordination between recombinational repair and DNA replication.
      This notion is further strengthened by the dramatic increase in the frequency of
      Rad52 focus formation observed in a pol12-100 replication mutant and a mec1 DNA
      damage checkpoint mutant. Furthermore, our data indicate that each Rad52 focus
      represents a center of recombinational repair capable of processing multiple DNA
      lesions.

PMID- 11459965
TI  - A yeast gene, MGS1, encoding a DNA-dependent AAA(+) ATPase is required to
      maintain genome stability.
AB  - Changes in DNA superhelicity during DNA replication are mediated primarily by the
      activities of DNA helicases and topoisomerases. If these activities are
      defective, the progression of the replication fork can be hindered or blocked,
      which can lead to double-strand breaks, elevated recombination in regions of
      repeated DNA, and genome instability. Hereditary diseases like Werner's and
      Bloom's Syndromes are caused by defects in DNA helicases, and these diseases are
      associated with genome instability and carcinogenesis in humans. Here we report a
      Saccharomyces cerevisiae gene, MGS1 (Maintenance of Genome Stability 1), which
      encodes a protein belonging to the AAA(+) class of ATPases, and whose central
      region is similar to Escherichia coli RuvB, a Holliday junction branch migration
      motor protein. The Mgs1 orthologues are highly conserved in prokaryotes and
      eukaryotes. The Mgs1 protein possesses DNA-dependent ATPase and single-strand DNA
      annealing activities. An mgs1 deletion mutant has an elevated rate of mitotic
      recombination, which causes genome instability. The mgs1 mutation is synergistic
      with a mutation in top3 (encoding topoisomerase III), and the double mutant
      exhibits severe growth defects and markedly increased genome instability. In
      contrast to the mgs1 mutation, a mutation in the sgs1 gene encoding a DNA
      helicase homologous to the Werner and Bloom helicases suppresses both the growth
      defect and the increased genome instability of the top3 mutant. Therefore,
      evolutionarily conserved Mgs1 may play a role together with RecQ family helicases
      and DNA topoisomerases in maintaining proper DNA topology, which is essential for
      genome stability.

PMID- 11459966
TI  - The tight linkage between DNA replication and double-strand break repair in
      bacteriophage T4.
AB  - Double-strand break (DSB) repair and DNA replication are tightly linked in the
      life cycle of bacteriophage T4. Indeed, the major mode of phage DNA replication
      depends on recombination proteins and can be stimulated by DSBs. DSB-stimulated
      DNA replication is dramatically demonstrated when T4 infects cells carrying two
      plasmids that share homology. A DSB on one plasmid triggered extensive
      replication of the second plasmid, providing a useful model for T4 recombination
      dependent replication (RDR). This system also provides a view of DSB repair in T4
      infected cells and revealed that the DSB repair products had been replicated in
      their entirety by the T4 replication machinery. We analyzed the detailed
      structure of these products, which do not fit the simple predictions of any of
      three models for DSB repair. We also present evidence that the T4 RDR system
      functions to restart stalled or inactivated replication forks. First, we review
      experiments involving antitumor drug-stabilized topoisomerase cleavage complexes.
      The results suggest that forks blocked at cleavage complexes are resolved by
      recombinational repair, likely involving RDR. Second, we show here that the
      presence of a T4 replication origin on one plasmid substantially stimulated
      recombination events between it and a homologous second plasmid that did not
      contain a T4 origin. Furthermore, replication of the second plasmid was increased
      when the first plasmid contained the T4 origin. Our interpretation is that origin
      initiated forks become inactivated at some frequency during replication of the
      first plasmid and are then restarted via RDR on the second plasmid.

PMID- 11459967
TI  - Mediator proteins orchestrate enzyme-ssDNA assembly during T4 recombination
      dependent DNA replication and repair.
AB  - Studies of recombination-dependent replication (RDR) in the T4 system have
      revealed the critical roles played by mediator proteins in the timely and
      productive loading of specific enzymes onto single-stranded DNA (ssDNA) during
      phage RDR processes. The T4 recombination mediator protein, uvsY, is necessary
      for the proper assembly of the T4 presynaptic filament (uvsX recombinase
      cooperatively bound to ssDNA), leading to the recombination-primed initiation of
      leading strand DNA synthesis. In the lagging strand synthesis component of RDR,
      replication mediator protein gp59 is required for the assembly of gp41, the DNA
      helicase component of the T4 primosome, onto lagging strand ssDNA. Together, uvsY
      and gp59 mediate the productive coupling of homologous recombination events to
      the initiation of T4 RDR. UvsY promotes presynaptic filament formation on 3'
      ssDNA-tailed chromosomes, the physiological primers for T4 RDR, and recent
      results suggest that uvsY also may serve as a coupling factor between presynapsis
      and the nucleolytic resection of double-stranded DNA ends. Other results indicate
      that uvsY stabilizes uvsX bound to the invading strand, effectively preventing
      primosome assembly there. Instead, gp59 directs primosome assembly to the
      displaced strand of the D loop/replication fork. This partitioning mechanism
      enforced by the T4 recombination/replication mediator proteins guards against
      antirecombination activity of the helicase component and ensures that
      recombination intermediates formed by uvsX/uvsY will efficiently be converted
      into semiconservative DNA replication forks. Although the major mode of T4 RDR is
      semiconservative, we present biochemical evidence that a conservative "bubble
      migration" mode of RDR could play a role in lesion bypass by the T4 replication
      machinery.

PMID- 11459968
TI  - Two recombination-dependent DNA replication pathways of bacteriophage T4, and
      their roles in mutagenesis and horizontal gene transfer.
AB  - Two major pathways of recombination-dependent DNA replication, "join-copy" and
      "join-cut-copy," can be distinguished in phage T4: join-copy requires only early
      and middle genes, but two late proteins, endonuclease VII and terminase, are
      uniquely important in the join-cut-copy pathway. In wild-type T4, timing of these
      pathways is integrated with the developmental program and related to
      transcription and packaging of DNA. In primase mutants, which are defective in
      origin-dependent lagging-strand DNA synthesis, the late pathway can bypass the
      lack of primers for lagging-strand DNA synthesis. The exquisitely regulated
      synthesis of endo VII, and of two proteins from its gene, explains the delay of
      recombination-dependent DNA replication in primase (as well as topoisomerase)
      mutants, and the temperature-dependence of the delay. Other proteins (e.g., the
      single-stranded DNA binding protein and the products of genes 46 and 47) are
      important in all recombination pathways, but they interact differently with other
      proteins in different pathways. These homologous recombination pathways
      contribute to evolution because they facilitate acquisition of any foreign DNA
      with limited sequence homology during horizontal gene transfer, without requiring
      transposition or site-specific recombination functions. Partial heteroduplex
      repair can generate what appears to be multiple mutations from a single
      recombinational intermediate. The resulting sequence divergence generates
      barriers to formation of viable recombinants. The multiple sequence changes can
      also lead to erroneous estimates in phylogenetic analyses.

PMID- 11459969
TI  - Bacteriophage T4 gene 41 helicase and gene 59 helicase-loading protein: a
      versatile couple with roles in replication and recombination.
AB  - Bacteriophage T4 uses two modes of replication initiation: origin-dependent
      replication early in infection and recombination-dependent replication at later
      times. The same relatively simple complex of T4 replication proteins is
      responsible for both modes of DNA synthesis. Thus the mechanism for loading the
      T4 41 helicase must be versatile enough to allow it to be loaded on R loops
      created by transcription at several origins, on D loops created by recombination,
      and on stalled replication forks. T4 59 helicase-loading protein is a small,
      basic, almost completely alpha-helical protein whose N-terminal domain has
      structural similarity to high mobility group family proteins. In this paper we
      review recent evidence that 59 protein recognizes specific structures rather than
      specific sequences. It binds and loads the helicase on replication forks and on
      three- and four-stranded (Holliday junction) recombination structures, without
      sequence specificity. We summarize our experiments showing that purified T4
      enzymes catalyze complete unidirectional replication of a plasmid containing the
      T4 ori(uvsY) origin, with a preformed R loop at the position of the R loop
      identified at this origin in vivo. This replication depends on the 41 helicase
      and is strongly stimulated by 59 protein. Moreover, the helicase-loading protein
      helps to coordinate leading and lagging strand synthesis by blocking replication
      on the ori(uvsY) R loop plasmid until the helicase is loaded. The T4 enzymes also
      can replicate plasmids with R loops that do not have a T4 origin sequence, but
      only if the R loops are within an easily unwound DNA sequence.

PMID- 11459970
TI  - Instability of repetitive DNA sequences: the role of replication in multiple
      mechanisms.
AB  - Rearrangements between tandem sequence homologies of various lengths are a major
      source of genomic change and can be deleterious to the organism. These
      rearrangements can result in either deletion or duplication of genetic material
      flanked by direct sequence repeats. Molecular genetic analysis of repetitive
      sequence instability in Escherichia coli has provided several clues to the
      underlying mechanisms of these rearrangements. We present evidence for three
      mechanisms of RecA-independent sequence rearrangements: simple replication
      slippage, sister-chromosome exchange-associated slippage, and single-strand
      annealing. We discuss the constraints of these mechanisms and contrast their
      properties with RecA-dependent homologous recombination. Replication plays a
      critical role in the two slipped misalignment mechanisms, and difficulties in
      replication appear to trigger rearrangements via all these mechanisms.

PMID- 11459971
TI  - Repeat expansion by homologous recombination in the mouse germ line at
      palindromic sequences.
AB  - Genetic instability can be induced by unusual DNA structures and sequence
      repeats. We have previously demonstrated that a large palindrome in the mouse
      germ line derived from transgene integration is extremely unstable and undergoes
      stabilizing rearrangements at high frequency, often through deletions that
      produce asymmetry. We have now characterized other palindrome rearrangements that
      arise from complex homologous recombination events. The structure of the
      recombinants is consistent with homologous recombination occurring by a
      noncrossover gene conversion mechanism in which a break induced in the palindrome
      promotes homologous strand invasion and repair synthesis, similar to mitotic
      break repair events reported in mammalian cells. Some of the homologous
      recombination events led to expansion in the size of the palindromic locus, which
      in the extreme case more than doubled the number of repeats. These results may
      have implications for instability observed at naturally occurring palindromic or
      quasipalindromic sequences.

PMID- 11459972
TI  - Stationary-phase mutation in the bacterial chromosome: recombination protein and
      DNA polymerase IV dependence.
AB  - Several microbial systems have been shown to yield advantageous mutations in
      slowly growing or nongrowing cultures. In one assay system, the stationary-phase
      mutation mechanism differs from growth-dependent mutation, demonstrating that the
      two are different processes. This system assays reversion of a lac frameshift
      allele on an F' plasmid in Escherichia coli. The stationary-phase mutation
      mechanism at lac requires recombination proteins of the RecBCD double-strand
      break repair system and the inducible error-prone DNA polymerase IV, and the
      mutations are mostly -1 deletions in small mononucleotide repeats. This mutation
      mechanism is proposed to occur by DNA polymerase errors made during replication
      primed by recombinational double-strand-break repair. It has been suggested that
      this mechanism is confined to the F plasmid. However, the cells that acquire the
      adaptive mutations show hypermutation of unrelated chromosomal genes, suggesting
      that chromosomal sites also might experience recombination protein-dependent
      stationary-phase mutation. Here we test directly whether the stationary-phase
      mutations in the bacterial chromosome also occur via a recombination protein- and
      pol IV-dependent mechanism. We describe an assay for chromosomal mutation in
      cells carrying the F' lac. We show that the chromosomal mutation is recombination
      protein- and pol IV-dependent and also is associated with general hypermutation.
      The data indicate that, at least in these male cells, recombination protein
      dependent stationary-phase mutation is a mechanism of general inducible genetic
      change capable of affecting genes in the bacterial chromosome.

PMID- 11459973
TI  - Managing DNA polymerases: coordinating DNA replication, DNA repair, and DNA
      recombination.
AB  - Two important and timely questions with respect to DNA replication, DNA
      recombination, and DNA repair are: (i) what controls which DNA polymerase gains
      access to a particular primer-terminus, and (ii) what determines whether a DNA
      polymerase hands off its DNA substrate to either a different DNA polymerase or to
      a different protein(s) for the completion of the specific biological process?
      These questions have taken on added importance in light of the fact that the
      number of known template-dependent DNA polymerases in both eukaryotes and in
      prokaryotes has grown tremendously in the past two years. Most notably, the
      current list now includes a completely new family of enzymes that are capable of
      replicating imperfect DNA templates. This UmuC-DinB-Rad30-Rev1 superfamily of DNA
      polymerases has members in all three kingdoms of life. Members of this family
      have recently received a great deal of attention due to the roles they play in
      translesion DNA synthesis (TLS), the potentially mutagenic replication over DNA
      lesions that act as potent blocks to continued replication catalyzed by
      replicative DNA polymerases. Here, we have attempted to summarize our current
      understanding of the regulation of action of DNA polymerases with respect to
      their roles in DNA replication, TLS, DNA repair, DNA recombination, and cell
      cycle progression. In particular, we discuss these issues in the context of the
      Gram-negative bacterium, Escherichia coli, that contains a DNA polymerase (Pol V)
      known to participate in most, if not all, of these processes.

PMID- 11459974
TI  - Roles of DNA polymerases V and II in SOS-induced error-prone and error-free
      repair in Escherichia coli.
AB  - DNA polymerase V, composed of a heterotrimer of the DNA damage-inducible UmuC and
      UmuD(2)(') proteins, working in conjunction with RecA, single-stranded DNA
      (ssDNA)-binding protein (SSB), beta sliding clamp, and gamma clamp loading
      complex, are responsible for most SOS lesion-targeted mutations in Escherichia
      coli, by catalyzing translesion synthesis (TLS). DNA polymerase II, the product
      of the damage-inducible polB (dinA ) gene plays a pivotal role in replication
      restart, a process that bypasses DNA damage in an error-free manner. Replication
      restart takes place almost immediately after the DNA is damaged (approximately 2
      min post-UV irradiation), whereas TLS occurs after pol V is induced approximately
      50 min later. We discuss recent data for pol V-catalyzed TLS and pol II-catalyzed
      replication-restart. Specific roles during TLS for pol V and each of its
      accessory factors have been recently determined. Although the precise molecular
      mechanism of pol II-dependent replication-restart remains to be elucidated, it
      has recently been shown to operate in conjunction with RecFOR and PriA proteins.

PMID- 11459975
TI  - Accuracy of lesion bypass by yeast and human DNA polymerase eta.
AB  - DNA polymerase eta (Pol eta) functions in the error-free bypass of UV-induced DNA
      lesions, and a defect in Pol eta in humans causes the cancer-prone syndrome, the
      variant form of xeroderma pigmentosum. Both yeast and human Pol eta replicate
      through a cis-syn thymine-thymine dimer (TT dimer) by inserting two As opposite
      the two Ts of the dimer. Pol eta, however, is a low-fidelity enzyme, and it
      misinserts nucleotides with a frequency of approximately 10(-2) to 10(-3)
      opposite the two Ts of the TT dimer as well as opposite the undamaged template
      bases. This low fidelity of nucleotide insertion seems to conflict with the role
      of Pol eta in the error-free bypass of UV lesions. To resolve this issue, we have
      examined the ability of human and yeast Pol eta to extend from paired and
      mispaired primer termini opposite a TT dimer by using steady-state kinetic
      assays. We find that Pol eta extends from mispaired primer termini on damaged and
      undamaged DNAs with a frequency of approximately 10(-2) to 10(-3) relative to
      paired primer termini. Thus, after the incorporation of an incorrect nucleotide,
      Pol eta would dissociate from the DNA rather than extend from the mispair. The
      resulting primer-terminal mispair then could be subject to proofreading by a 3'-
      >5' exonuclease. Replication through a TT dimer by Pol eta then would be more
      accurate than that predicted from the fidelity of nucleotide incorporation alone.

PMID- 11459976
TI  - ATP bound to the origin recognition complex is important for preRC formation.
AB  - The origin recognition complex (ORC) binds origins of replication and directs the
      assembly of a higher order protein complex at these sites. ORC binds and
      hydrolyzes ATP in vitro. ATP binding to the largest subunit of ORC, Orc1p,
      stimulates specific binding to origin DNA; however, the function of ATP
      hydrolysis by ORC is unknown. To address the role of ATP hydrolysis, we have
      generated mutants within Orc1p that are dominant lethal. At physiological ATP
      concentrations, these mutants are defective for ATP hydrolysis but not ATP
      binding in the absence of DNA. These mutants inhibit formation of the
      prereplicative complex when overexpressed. The dominant lethal phenotype of these
      mutant ORC complexes is suppressed by simultaneous overexpression of wild-type,
      but not mutant, Cdc6p. Our findings suggest that these hydrolysis-defective
      mutants inhibit growth by titrating Cdc6p away from the origin. Based on these
      observations, we propose that Cdc6p specifically recognizes the ATP-bound state
      of Orc1p and that ATP hydrolysis is coupled to preRC disassembly.

PMID- 11459977
TI  - Creating a dynamic picture of the sliding clamp during T4 DNA polymerase
      holoenzyme assembly by using fluorescence resonance energy transfer.
AB  - The coordinated assembly of the DNA polymerase (gp43), the sliding clamp (gp45),
      and the clamp loader (gp44/62) to form the bacteriophage T4 DNA polymerase
      holoenzyme is a multistep process. A partially opened toroid-shaped gp45 is
      loaded around DNA by gp44/62 in an ATP-dependent manner. Gp43 binds to this
      complex to generate the holoenzyme in which gp45 acts to topologically link gp43
      to DNA, effectively increasing the processivity of DNA replication. Stopped-flow
      fluorescence resonance energy transfer was used to investigate the opening and
      closing of the gp45 ring during holoenzyme assembly. By using two site-specific
      mutants of gp45 along with a previously characterized gp45 mutant, we tracked
      changes in distances across the gp45 subunit interface through seven
      conformational changes associated with holoenzyme assembly. Initially, gp45 is
      partially open within the plane of the ring at one of the three subunit
      interfaces. On addition of gp44/62 and ATP, this interface of gp45 opens further
      in-plane through the hydrolysis of ATP. Addition of DNA and hydrolysis of ATP
      close gp45 in an out-of-plane conformation. The final holoenzyme is formed by the
      addition of gp43, which causes gp45 to close further in plane, leaving the
      subunit interface open slightly. This open interface of gp45 in the final
      holoenzyme state is proposed to interact with the C-terminal tail of gp43,
      providing a point of contact between gp45 and gp43. This study further defines
      the dynamic process of bacteriophage T4 polymerase holoenzyme assembly.

PMID- 11459978
TI  - Interaction of the beta sliding clamp with MutS, ligase, and DNA polymerase I.
AB  - The beta and proliferating cell nuclear antigen (PCNA) sliding clamps were first
      identified as components of their respective replicases, and thus were assigned a
      role in chromosome replication. Further studies have shown that the eukaryotic
      clamp, PCNA, interacts with several other proteins that are involved in excision
      repair, mismatch repair, cellular regulation, and DNA processing, indicating a
      much wider role than replication alone. Indeed, the Escherichia coli beta clamp
      is known to function with DNA polymerases II and V, indicating that beta also
      interacts with more than just the chromosomal replicase, DNA polymerase III. This
      report demonstrates three previously undetected protein-protein interactions with
      the beta clamp. Thus, beta interacts with MutS, DNA ligase, and DNA polymerase I.
      Given the diverse use of these proteins in repair and other DNA transactions,
      this expanded list of beta interactive proteins suggests that the prokaryotic
      beta ring participates in a wide variety of reactions beyond its role in
      chromosomal replication.

PMID- 11459979
TI  - Defining the roles of individual residues in the single-stranded DNA binding site
      of PcrA helicase.
AB  - Crystal structures and biochemical analyses of PcrA helicase provide evidence for
      a model for processive DNA unwinding that involves coupling of single-stranded
      DNA (ssDNA) tracking to a duplex destabilization activity. The DNA tracking model
      invokes ATP-dependent flipping of bases between several pockets on the enzyme
      formed by conserved aromatic amino acid residues. We have used site-directed
      mutagenesis to confirm the requirement of all of these residues for helicase
      activity. We also demonstrate that the duplex unwinding defects correlate with an
      inability of certain mutant proteins to translocate effectively on ssDNA.
      Moreover, the results define an essential triad of residues within the ssDNA
      binding site that comprise the ATP-driven DNA motor itself.

PMID- 11459980
TI  - Homologous DNA recombination in vertebrate cells.
AB  - The RAD52 epistasis group genes are involved in homologous DNA recombination, and
      their primary structures are conserved from yeast to humans. Although biochemical
      studies have suggested that the fundamental mechanism of homologous DNA
      recombination is conserved from yeast to mammals, recent studies of vertebrate
      cells deficient in genes of the RAD52 epistasis group reveal that the role of
      each protein is not necessarily the same as that of the corresponding yeast gene
      product. This review addresses the roles and mechanisms of homologous
      recombination-mediated repair with a special emphasis on differences between
      yeast and vertebrate cells.

PMID- 11459981
TI  - Meiotic recombination and chromosome segregation in Schizosaccharomyces pombe.
AB  - In most organisms homologous recombination is vital for the proper segregation of
      chromosomes during meiosis, the formation of haploid sex cells from diploid
      precursors. This review compares meiotic recombination and chromosome segregation
      in the fission yeast Schizosaccharomyces pombe and the distantly related budding
      yeast Saccharomyces cerevisiae, two especially tractable microorganisms. Certain
      features, such as the occurrence of DNA breaks associated with recombination,
      appear similar, suggesting that these features may be common in eukaryotes. Other
      features, such as the role of these breaks and the ability of chromosomes to
      segregate faithfully in the absence of recombination, appear different,
      suggesting multiple solutions to the problems faced in meiosis.

PMID- 11459982
TI  - Manipulating the mammalian genome by homologous recombination.
AB  - Gene targeting in mammalian cells has proven invaluable in biotechnology, in
      studies of gene structure and function, and in understanding chromosome dynamics.
      It also offers a potential tool for gene-therapeutic applications. Two
      limitations constrain the current technology: the low rate of homologous
      recombination in mammalian cells and the high rate of random (nontargeted)
      integration of the vector DNA. Here we consider possible ways to overcome these
      limitations within the framework of our present understanding of recombination
      mechanisms and machinery. Several studies suggest that transient alteration of
      the levels of recombination proteins, by overexpression or interference with
      expression, may be able to increase homologous recombination or decrease random
      integration, and we present a list of candidate genes. We consider potentially
      beneficial modifications to the vector DNA and discuss the effects of methods of
      DNA delivery on targeting efficiency. Finally, we present work showing that gene
      specific DNA damage can stimulate local homologous recombination, and we discuss
      recent results with two general methodologies--chimeric nucleases and triplex
      forming oligonucleotides--for stimulating recombination in cells.

PMID- 11459983
TI  - Assembly of RecA-like recombinases: distinct roles for mediator proteins in
      mitosis and meiosis.
AB  - Members of the RecA family of recombinases from bacteriophage T4, Escherichia
      coli, yeast, and higher eukaryotes function in recombination as higher-order
      oligomers assembled on tracts of single-strand DNA (ssDNA). Biochemical studies
      have shown that assembly of recombinase involves accessory factors. These studies
      have identified a class of proteins, called recombination mediator proteins, that
      act by promoting assembly of recombinase on ssDNA tracts that are bound by ssDNA
      binding protein (ssb). In the absence of mediators, ssb inhibits recombination
      reactions by competing with recombinase for DNA-binding sites. Here we briefly
      review mediated recombinase assembly and present results of new in vivo
      experiments. Immuno-double-staining experiments in Saccharomyces cerevisiae
      suggest that Rad51, the eukaryotic recombinase, can assemble at or near sites
      containing ssb (replication protein A, RPA) during the response to DNA damage,
      consistent with a need for mediator activity. Correspondingly, mediator gene
      mutants display defects in Rad51 assembly after DNA damage and during meiosis,
      although the requirements for assembly are distinct in the two cases. In meiosis,
      both Rad52 and Rad55/57 are required, whereas either Rad52 or Rad55/57 is
      sufficient to promote assembly of Rad51 in irradiated mitotic cells. Rad52
      promotes normal amounts of Rad51 assembly in the absence of Rad55 at 30 degrees C
      but not 20 degrees C, accounting for the cold sensitivity of rad55 null mutants.
      Finally, we show that assembly of Rad51 is induced by radiation during S phase
      but not during G(1), consistent with the role of Rad51 in repairing the
      spontaneous damage that occurs during DNA replication.

PMID- 11459984
TI  - Domain structure and dynamics in the helical filaments formed by RecA and Rad51
      on DNA.
AB  - Both the bacterial RecA protein and the eukaryotic Rad51 protein form helical
      nucleoprotein filaments on DNA that catalyze strand transfer between two
      homologous DNA molecules. However, only the ATP-binding cores of these proteins
      have been conserved, and this same core is also found within helicases and the F1
      ATPase. The C-terminal domain of the RecA protein forms lobes within the helical
      RecA filament. However, the Rad51 proteins do not have the C-terminal domain
      found in RecA, but have an N-terminal extension that is absent in the RecA
      protein. Both the RecA C-terminal domain and the Rad51 N-terminal domain bind
      DNA. We have used electron microscopy to show that the lobes of the yeast and
      human Rad51 filaments appear to be formed by N-terminal domains. These lobes are
      conformationally flexible in both RecA and Rad51. Within RecA filaments, the
      change between the "active" and "inactive" states appears to mainly involve a
      large movement of the C-terminal lobe. The N-terminal domain of Rad51 and the C
      terminal domain of RecA may have arisen from convergent evolution to play similar
      roles in the filaments.

PMID- 11459985
TI  - Homologous genetic recombination as an intrinsic dynamic property of a DNA
      structure induced by RecA/Rad51-family proteins: a possible advantage of DNA over
      RNA as genomic material.
AB  - Heteroduplex joints are general intermediates of homologous genetic recombination
      in DNA genomes. A heteroduplex joint is formed between a single-stranded region
      (or tail), derived from a cleaved parental double-stranded DNA, and homologous
      regions in another parental double-stranded DNA, in a reaction mediated by the
      RecA/Rad51-family of proteins. In this reaction, a RecA/Rad51-family protein
      first forms a filamentous complex with the single-stranded DNA, and then
      interacts with the double-stranded DNA in a search for homology. Studies of the
      three-dimensional structures of single-stranded DNA bound either to Escherichia
      coli RecA or Saccharomyces cerevisiae Rad51 have revealed a novel extended DNA
      structure. This structure contains a hydrophobic interaction between the 2'
      methylene moiety of each deoxyribose and the aromatic ring of the following base,
      which allows bases to rotate horizontally through the interconversion of sugar
      puckers. This base rotation explains the mechanism of the homology search and
      base-pair switch between double-stranded and single-stranded DNA during the
      formation of heteroduplex joints. The pivotal role of the 2' methylene-base
      interaction in the heteroduplex joint formation is supported by comparing the
      recombination of RNA genomes with that of DNA genomes. Some simple organisms with
      DNA genomes induce homologous recombination when they encounter conditions that
      are unfavorable for their survival. The extended DNA structure confers a dynamic
      property on the otherwise chemically and genetically stable double-stranded DNA,
      enabling gene segment rearrangements without disturbing the coding frame (i.e.,
      protein-segment shuffling). These properties may give an extensive evolutionary
      advantage to DNA.

PMID- 11459986
TI  - The synaptic activity of HsDmc1, a human recombination protein specific to
      meiosis.
AB  - Human Dmc1 protein, a meiosis-specific homolog of Escherichia coli RecA protein,
      has previously been shown to promote DNA homologous pairing and strand-exchange
      reactions that are qualitatively similar to those of RecA protein and Rad51.
      Human and yeast Rad51 proteins each form a nucleoprotein filament that is very
      similar to the filament formed by RecA protein. However, recent studies failed to
      find a similar filament made by Dmc1 but showed instead that this protein forms
      octameric rings and stacks of rings. These observations stimulated further
      efforts to elucidate the mechanism by which Dmc1 promotes the recognition of
      homology. Dmc1, purified to a state in which nuclease and helicase activities
      were undetectable, promoted homologous pairing and strand exchange as measured by
      fluorescence resonance energy transfer (FRET). Observations on the intermediates
      and products, which can be distinguished by FRET assays, provided direct evidence
      of a three-stranded synaptic intermediate. The effects of helix stability and
      mismatched base pairs on the recognition of homology revealed further that human
      Dmc1, like human Rad51, requires the preferential breathing of A small middle
      dotT base pairs for recognition of homology. We conclude that Dmc1, like human
      Rad51 and E. coli RecA protein, promotes homologous pairing and strand exchange
      by a "synaptic pathway" involving a three-stranded nucleoprotein intermediate,
      rather than by a "helicase pathway" involving the separation and reannealing of
      DNA strands.

PMID- 11459987
TI  - Complex formation by the human RAD51C and XRCC3 recombination repair proteins.
AB  - In vertebrates, the RAD51 protein is required for genetic recombination, DNA
      repair, and cellular proliferation. Five paralogs of RAD51, known as RAD51B,
      RAD51C, RAD51D, XRCC2, and XRCC3, have been identified and also shown to be
      required for recombination and genome stability. At the present time, however,
      very little is known about their biochemical properties or precise biological
      functions. As a first step toward understanding the roles of the RAD51 paralogs
      in recombination, the human RAD51C and XRCC3 proteins were overexpressed and
      purified from baculovirus-infected insect cells. The two proteins copurify as a
      complex, a property that reflects their endogenous association observed in HeLa
      cells. Purified RAD51C--XRCC3 complex binds single-stranded, but not duplex DNA,
      to form protein--DNA networks that have been visualized by electron microscopy.

PMID- 11459988
TI  - Rad54 protein stimulates the postsynaptic phase of Rad51 protein-mediated DNA
      strand exchange.
AB  - Rad54 and Rad51 are important proteins for the repair of double-stranded DNA
      breaks by homologous recombination in eukaryotes. As previously shown, Rad51
      protein forms nucleoprotein filaments on single-stranded DNA, and Rad54 protein
      directly interacts with such filaments to enhance synapsis, the homologous
      pairing with a double-stranded DNA partner. Here we demonstrate that
      Saccharomyces cerevisiae Rad54 protein has an additional role in the postsynaptic
      phase of DNA strand exchange by stimulating heteroduplex DNA extension of
      established joint molecules in Rad51/Rpa-mediated DNA strand exchange. This
      function depended on the ATPase activity of Rad54 protein and on specific
      protein:protein interactions between the yeast Rad54 and Rad51 proteins.

PMID- 11459989
TI  - The architecture of the human Rad54-DNA complex provides evidence for protein
      translocation along DNA.
AB  - Proper maintenance and duplication of the genome require accurate recombination
      between homologous DNA molecules. In eukaryotic cells, the Rad51 protein mediates
      pairing between homologous DNA molecules. This reaction is assisted by the Rad54
      protein. To gain insight into how Rad54 functions, we studied the interaction of
      the human Rad54 (hRad54) protein with double-stranded DNA. We have recently shown
      that binding of hRad54 to DNA induces a change in DNA topology. To determine
      whether this change was caused by a protein-constrained change in twist, a
      protein-constrained change in writhe, or the introduction of unconstrained
      plectonemic supercoils, we investigated the hRad54--DNA complex by scanning force
      microscopy. The architecture of the observed complexes suggests that movement of
      the hRad54 protein complex along the DNA helix generates unconstrained
      plectonemic supercoils. We discuss how hRad54-induced superhelical stress in the
      target DNA may function to facilitate homologous DNA pairing by the hRad51
      protein directly. In addition, the induction of supercoiling by hRad54 could
      stimulate recombination indirectly by displacing histones and/or other proteins
      packaging the DNA into chromatin. This function of DNA translocating motors might
      be of general importance in chromatin metabolism.

PMID- 11459991
TI  - Excited-state dynamics in photosystem II: insights from the x-ray crystal
      structure.
AB  - The heart of oxygenic photosynthesis is photosystem II (PSII), a multisubunit
      protein complex that uses solar energy to drive the splitting of water and
      production of molecular oxygen. The effectiveness of the photochemical reaction
      center of PSII depends on the efficient transfer of excitation energy from the
      surrounding antenna chlorophylls. A kinetic model for PSII, based on the x-ray
      crystal structure coordinates of 37 antenna and reaction center pigment
      molecules, allows us to map the major energy transfer routes from the antenna
      chlorophylls to the reaction center chromophores. The model shows that energy
      transfer to the reaction center is slow compared with the rate of primary
      electron transport and depends on a few bridging chlorophyll molecules. This
      unexpected energetic isolation of the reaction center in PSII is similar to that
      found in the bacterial photosystem, conflicts with the established view of the
      photophysics of PSII, and may be a functional requirement for primary
      photochemistry in photosynthesis. In addition, the model predicts a value for the
      intrinsic photochemical rate constant that is 4 times that found in bacterial
      reaction centers.

PMID- 11459990
TI  - DNA replication meets genetic exchange: chromosomal damage and its repair by
      homologous recombination.
AB  - Proceedings of the National Academy of Sciences Colloquium on the roles of
      homologous recombination in DNA replication are summarized. Current findings in
      experimental systems ranging from bacteriophages to mammalian cell lines
      substantiate the idea that homologous recombination is a system supporting DNA
      replication when either the template DNA is damaged or the replication machinery
      malfunctions. There are several lines of supporting evidence: (i) DNA replication
      aggravates preexisting DNA damage, which then blocks subsequent replication; (ii)
      replication forks abandoned by malfunctioning replisomes become prone to
      breakage; (iii) mutants with malfunctioning replisomes or with elevated levels of
      DNA damage depend on homologous recombination; and (iv) homologous recombination
      primes DNA replication in vivo and can restore replication fork structures in
      vitro. The mechanisms of recombinational repair in bacteriophage T4, Escherichia
      coli, and Saccharomyces cerevisiae are compared. In vitro properties of the
      eukaryotic recombinases suggest a bigger role for single-strand annealing in the
      eukaryotic recombinational repair.

PMID- 11459992
TI  - Computer-modeling origin of a simple genetic apparatus.
AB  - This computer simulation is based on a model of the origin of life proposed by H.
      Kuhn and J. Waser, where the evolution of short molecular strands is assumed to
      take place in a distinct spatiotemporal structured environment. In their model,
      the prebiotic situation is strongly simplified to grasp essential features of the
      evolution of the genetic apparatus without attempts to trace the historic path.
      With the tool of computer implementation confining to principle aspects and
      focused on critical features of the model, a deeper understanding of the model's
      premises is achieved. Each generation consists of three steps: (i) construction
      of devices (entities exposed to selection) presently available; (ii) selection;
      and (iii) multiplication of the isolated strands (R oligomers) by complementary
      copying with occasional variation by copying mismatch. In the beginning, the
      devices are single strands with random sequences; later, increasingly complex
      aggregates of strands form devices such as a hairpin-assembler device which
      develop in favorable cases. A monomers interlink by binding to the hairpin
      assembler device, and a translation machinery, called the hairpin-assembler
      enzyme device, emerges, which translates the sequence of R(1) and R(2) monomers
      in the assembler strand to the sequence of A(1) and A(2) monomers in the A
      oligomer, working as an enzyme.

PMID- 11459993
TI  - Demonstration of the extrinsic coagulation pathway in teleostei: identification
      of zebrafish coagulation factor VII.
AB  - It is not known whether the mammalian mechanism of coagulation initiation is
      conserved in fish. Identification of factor VII is critical in providing evidence
      for such a mechanism. A cDNA was cloned from a zebrafish (teleost) library that
      predicted a protein with sequence similarity to human factor VII. Factor VII was
      shown to be present in zebrafish blood and liver by Western blot analysis and
      immunohistochemistry. Immunodepletion of factor VII from zebrafish plasma
      selectively inhibited thromboplastin-triggered thrombin generation. Heterologous
      expression of zebrafish factor VII demonstrated a secreted protein (50 kDa) that
      reconstituted thromboplastin-triggered thrombin generation in immunodepleted
      zebrafish plasma. These results suggest conservation of the extrinsic coagulation
      pathway between zebrafish and humans and add credence to the zebrafish as a model
      for mammalian hemostasis. The structure of zebrafish factor VIIa predicted by
      homology modeling was consistent with the overall three-dimensional structure of
      human factor VIIa. However, amino acid disparities were found in the epidermal
      growth factor-2/serine protease regions that are present in the human tissue
      factor-factor VIIa contact surface, suggesting a structural basis for the species
      specificity of this interaction. In addition, zebrafish factor VII demonstrates
      that the Gla-EGF-EGF-SP domain structure, which is common to coagulation factors
      VII, IX, X, and protein C, was present before the radiation of the teleosts from
      the tetrapods. Identification of zebrafish factor VII significantly narrows the
      evolutionary window for development of the vertebrate coagulation cascade and
      provides insight into the structural basis for species specificity in the tissue
      factor-factor VIIa interaction.

PMID- 11459994
TI  - Raltitrexed/5-fluorouracil-based combination chemotherapy regimens in anticancer
      therapy.
AB  - Preclinical evidence of a schedule-dependent synergism between raltitrexed and 5
      fluorouracil (5-FU) has prompted clinical studies of this combination. We review
      the main preclinical and clinical results of raltitrexed/5-FU-based combination
      chemotherapy regimens in anticancer therapy. Promising results include: response
      rates of 25 and 23% with combinations of raltitrexed/5-FU/levofolinic acid (LFA)
      as first-line treatment and oxaliplatin/raltitrexed/5-FU/LFA as second-line
      treatment of metastatic colorectal cancer, respectively; and a 67% response rate
      in a phase I study of cisplatin/raltitrexed/5-FU/LFA as first-line treatment of
      advanced head and neck cancer, including a 100% response rate at the recommended
      dose. These combinations were well tolerated, with neutropenia as the main dose
      limiting toxicity, allowing the drugs to be combined at the doses used in
      monotherapy. These results suggest a role for raltitrexed within combination
      regimens in colorectal cancer therapy, as well as other tumors such as head and
      neck cancer. A further potential application of raltitrexed in combination
      therapies is within multidisciplinary chemo-radiotherapy strategies, mainly in
      rectal cancer. Phase II studies are planned/ongoing to investigate these
      interesting possibilities.

PMID- 11459995
TI  - Phase I trial of i.v. administered tirapazamine plus cyclophosphamide.
AB  - Our objective was to determine the maximum tolerated doses of tirapazamine and
      cyclophosphamide given i.v. in combination. Eligible patients had advanced solid
      tumors refractory to conventional treatment. Tirapazamine (escalated from 80 to
      390 mg/m(2)) was given i.v. over 2 h and followed by cyclophosphamide over 1 h.
      The cyclophosphamide dose was fixed at 1000 mg/m(2) until the tirapazamine dose
      of 390 mg/m(2) was reached. Once that dose of tirapazamine was reached, the
      cyclophosphamide dose was escalated to 1250 and 1500 mg/m(2). Twenty-eight
      patients were enrolled. The dose-limiting toxicity was granulocytopenia. One
      patient had transient deafness for 2 days. Four other patients had grade 1
      ototoxicity. Grade 1 and 2 muscle cramps were observed at all dose levels. Other
      toxic effects observed included fatigue, nausea, vomiting, headache, diarrhea,
      drug fever, elevated transaminases and elevated creatine phosphokinase. Three
      patients had stable disease and the longest time to progression was 5 months. The
      combination of tirapazamine and cyclophosphamide is feasible, and the dose
      limiting toxicity is granulocytopenia. The use of growth factors could possibly
      allow escalation of tirapazamine doses in future phase II trials. Without growth
      factor support, the recommended doses of tirapazamine and cyclophosphamide when
      administered in this schedule are 260 and 1000 mg/m(2), respectively.

PMID- 11459996
TI  - Phase I and pharmacologic study of i.v. hydroxyurea infusion given with i.p. 5
      fluoro-2'-deoxyuridine and leucovorin.
AB  - Preclinical data suggests that the action of fluoropyrimidines may be enhanced by
      the addition of hydroxyurea. We developed a phase I trial to determine the
      maximum tolerated dose and pharmacokinetics of i.v. hydroxyurea (HU) in
      combination with i.p. 5-fluoro-2'-deoxyuridine (FUdR) and leucovorin (LV).
      Eligible patients had metastatic carcinoma confined mostly to the peritoneal
      cavity, and adequate hepatic, renal and bone marrow function. Patients were
      treated with a fixed dose of FUdR (3 g) and LV (640 mg) administered on days 1-
      3. HU was administered as a 72-h infusion starting simultaneously with i.p.
      therapy on day 1. The following dose levels were studied: 2.0, 2.5, 3.0 and 3.6
      g/m(2)/day. Pharmacokinetics were studied in blood and peritoneal fluid. Twenty
      eight patients were accrued. Steady-state plasma and peritoneal fluid HU levels
      increased with increasing dose, and steady state was achieved within 12 h of
      continuous dosing. The steady-state HU plasma:peritoneal fluid concentration
      ratio ranged from 1.06 x 10(3) to 1.25 x 10(3) and the plasma HU clearance ranged
      from 4.63 to 5.81 l/h/m(2). Peritoneal fluid AUC = 137,639 +/- 43,914 microg/ml x
      min, t(1/2) = 100.9 +/- 56.4 min and Cl = 25.29 +/- 10.88 ml/min. Neutropenia
      represented the dose-limiting toxicity. We conclude that i.p. FUdR and LV in
      combination with i.v. HU is well tolerated. The addition of systemic HU increased
      the incidence of myelosuppression.

PMID- 11459997
TI  - Phase II study of the combination cisplatin, etoposide, 5-fluorouracil and
      folinic acid in patients with advanced squamous cell carcinoma of the esophagus.
AB  - The objective of this study was to determine the toxicity and the efficacy of the
      combination of cisplatin, etoposide, 5-fluorouracil (5-FU) and folinic acid in
      the treatment of patients with advanced squamous cell carcinoma of the esophagus.
      Patients received cisplatin 80 mg/m(2) i.v. on day 1, etoposide 125 mg/m(2) i.v.
      on day 1 and etoposide 200 mg/m(2) p.o. on days 3 and 5, 5-FU 375 mg/m(2)/day
      continuously i.v. combined with folinic acid 30 mg p.o. 6 times per day on days 1
      -4. Courses were repeated every 4 weeks until progression or up to a maximum of 6
      courses. Patients were evaluated for response after every two courses. Sixty-nine
      patients received a total of 291 courses (median 4, range 1--6). The
      hematological toxicity consisted of leukocytopenia grade 3 or 4 in 17 and 16% of
      patients, respectively. Leukocytopenic fever was seen in 19% of patients.
      Thrombocytopenia grade 3 or 4 was seen in 13 and 7% of patients, respectively.
      Non-hematological toxicity consisted of nausea/vomiting grade 3 in 32%, diarrhea
      grade 3 in 6% and mucositis grade 3 or 4 in 23% of patients. The overall response
      rate was 34% (complete response 4%, partial response 30%) and the median time to
      progression was 7 months in 13 patients who received no additional treatment. The
      median survival for all patients was 9.5 months with a 1-year survival rate of
      36%. Ten patients with initially locally unresectable disease (N=2) or celiac or
      supraclavicular lymph node metastases (N=8) who received additional treatment
      (esophageal resection in seven patients and radiotherapy in three patients) after
      they had responded to chemotherapy had a 3-year survival of 50%. We conclude that
      the combination cisplatin and etoposide combined with 5-FU and folinic acid is a
      safe and active regimen for patients with advanced squamous cell carcinoma of the
      esophagus. Mucositis is the most prevalent toxicity.

PMID- 11459998
TI  - Urinary excretion of thioTEPA and its metabolites in patients treated with high
      dose cyclophosphamide, thioTEPA and carboplatin.
AB  - The urinary excretion of N,N',N"-triethylenethiophosphoramide (thioTEPA), and its
      metabolites N,N',N"-triethylenephosphoramide (TEPA), N,N'-diethylene,N"-2
      chloroethylphosphoramide (monochloroTEPA) and thioTEPA--mercapturate was
      determined in patients receiving thioTEPA as part of a high-dose combination
      chemotherapy regimen with cyclophosphamide and carboplatin. The thioTEPA dose was
      40 or 60 mg/m(2) in short infusions, twice daily, during 4 days. Urine samples
      were collected after each voiding on each day of drug administration until 24--48
      h after the last thioTEPA infusion. ThioTEPA, TEPA and monochloroTEPA
      concentrations were determined with gas chromatography and thioTEPA--mercapturate
      with liquid chromatography--mass spectrometry with direct sample injection.
      ThioTEPA was present in urine 30 min after infusion and was still excreted 18 h
      after the last infusion. All metabolites were detected in urine 1 h after
      infusion. Patients with a creatinine clearance above 140 ml/minl showed higher
      excretion of TEPA than patients with a creatinine clearance below 140 ml/min
      (12.8 versus 4.9%, p=0.01). The excretion of monochloroTEPA relative to the
      excreted amount of TEPA increased at lower pH values of the urine. The excretion
      of thioTEPA--mercapturate relative to the dose was higher in patients treated
      with 60 mg/m(2). Excretion of thioTEPA and monochloroTEPA both accounted for only
      0.5% of the dose, while TEPA and thioTEPA--mercapturate both accounted for 11.1%.

PMID- 11459999
TI  - Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and
      eniluracil.
AB  - 5-Fluorouracil (5-FU)-associated neurotoxicity is uncommon; symptoms may occur
      abruptly or more gradually during the course of chemotherapy. Peripheral
      neuropathy with 5-FU therapy has only rarely been reported. Two patients treated
      in a phase I trial of oral 5-FU, leucovorin and eniluracil, an inhibitor of
      dihydropyrimidine dehydrogenase (DPD), developed delayed onset symptoms of
      unsteady gait and reduced sensation in the legs. Magnetic resonance imaging scans
      of the brain and neurologic examination did not support a CNS basis for the
      condition. Electromyograms and nerve conduction studies revealed sensorimotor
      polyneuropathy. Other common etiologies of peripheral neuropathy were excluded.
      The neurological condition of these patients stabilized after 5-FU dose reduction
      and partial resolution gradually occurred when protocol therapy was stopped.
      Although CNS symptoms may rarely complicate 5-FU therapy, peripheral neuropathy
      is unexpected. Patients with DPD deficiency treated with conventional doses of 5
      FU typically develop acute CNS toxicity shortly after therapy, accompanied by
      extremely high systemic exposure to 5-FU. Patients with normal 5-FU clearance may
      also experience CNS toxicity, particularly with high-dose schedules, and both
      parent drug and its catabolites may be contributory. Since DPD was profoundly
      inhibited during eniluracil therapy in these two patients, it is likely that 5-FU
      or its active metabolites were contributing factors to the peripheral neuropathy.

PMID- 11460000
TI  - A cost--utility analysis comparing second-line chemotherapy schemes in patients
      with metastatic breast cancer.
AB  - A cost-utility analysis has been performed comparing taxanes, vinorelbine and
      standard therapy for metastatic breast cancer considering clinical efficacy,
      quality-adjusted-life-years (QALYs) and costs. A decision model has been built.
      Clinical efficacy data were collected by literature review. Utility data and cost
      data were collected from previous studies and Dutch wholesale prices. Except for
      the MV standard therapy, VM has the lowest C/E ratio of $17,114/QALY, followed by
      paclitaxel ($30,270/QALY) and docetaxel ($49,739/QALY). VM yields the highest
      number of QALYs (0.47), compared to paclitaxel (0.35), docetaxel (0.34) and MV
      (0.29). Compared to the MV standard therapy, the incremental C/E of VM is
      $23,046/QALY, which is the lowest of all alternatives. We conclude that compared
      to paclitaxel, docetaxel and MV standard chemotherapy, VM is the most cost
      effective second-line chemotherapy for metastatic breast cancer patients. There
      is a considerable variation in utility scores, depending on the methods or the
      data sources used. The C/E ratios were influenced most strongly by drug prices,
      utility and efficacy (in descending order of importance).

PMID- 11460001
TI  - Methyl protogracillin (NSC-698792): the spectrum of cytotoxicity against 60 human
      cancer cell lines in the National Cancer Institute's anticancer drug screen
      panel.
AB  - Methyl protogracillin (NSC-698792) was a furostanol saponin isolated from the
      rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal
      remedy for the treatment of cervical carcinoma, carcinoma of urinary bladder and
      renal tumor for centuries, in our previous studies. In order to systematically
      evaluate its potential anticancer activity, methyl protogracillin was tested for
      its cytotoxicity in vitro against 60 human cancer cell lines in the National
      Cancer Institute (NCI)'s anticancer drug screen. As a result, it was found that
      methyl protogracillin was cytotoxic against all the tested cell lines from
      leukemia and solid tumors in the NCI's human cancer panel; it showed particular
      selectivity against one colon cancer line (KM12), one central nervous system
      (CNS) cancer line (U251), two melanoma lines (MALME-3M and M14), two renal cancer
      lines (786-0 and UO-31) and one breast cancer line (MDA-MB-231) with GI50< or
      =2.0 microM. The selectivity between these seven most sensitive lines and the
      least sensitive line (CCRF-CEM) ranged from 26- to 56-fold. In the same cancer
      subpanel, selectivity more than 15-fold was observed between MDA-MB-231 and MCF
      7, NCI-ADR-RES, BT-549 in breast cancer. From a general view of the mean graph,
      CNS cancer is the most sensitive subpanel, while ovarian cancer and renal cancer
      are the least sensitive subpanels. Based on an analysis of the COMPARE computer
      program with methyl protogracillin as a seed compound, no compounds in the NCI's
      anticancer drug screen database have similar cytotoxicity patterns (mean graph)
      to that of methyl protogracillin, indicating a potential novel mechanism of the
      anticancer action involved.

PMID- 11460002
TI  - Relationship between cytocidal activity and glutathione-S-transferase inhibition
      using doxorubicin coupled to stereoisomers of glutathione with different
      substrate specificity.
AB  - To determine the cytotoxic mode of action of a glutathione (GSH)--doxorubicin
      (DXR) conjugate, which exhibited potent cytotoxicity against various multidrug
      resistant as well as DXR-sensitive cell lines, the molecular interaction between
      covalent GSH--DXR conjugates and glutathione-S-transferase (GST), a possible
      molecular target of the conjugates, was investigated. The following four GSH
      molecules with stereoisomeric forms were prepared: L-Glu--L-Cys--Gly (LL-GSH), D
      Glu--L-Cys--Gly (DL-GSH), L-Glu--D-Cys--Gly (LD-GSH) and D-Glu--D-Cys--Gly (DD
      GSH). The enzymic activity of GST against each GSH stereoisomer was 88, 38, 8 and
      4 nmol/mg/min, respectively, suggesting that the L-form cysteine residue in the
      molecule was an important substrate of GST. Addition of DXR conjugated with each
      isomer (10 microM) to a GSH-containing GST assay mixture inhibited the GST
      activity to 32% for LL-GSH--XR, 16% for DL-GSH-DXR and 61% for LD-GSH-DXR as
      compared with the solvent control. Moreover, IC50 values for these conjugates
      were 30, 20 and 250 nM, respectively. The cytocidal activity of each conjugate
      corresponded to the substrate specificity of GST activity for the GSH isomer.
      These conjugates bound to the GST molecule, and the binding ability was 0.746,
      0.627 and 0.462 mol/mol of GST for LL-GSH--XR, DL-GSH-DXR and LD-GSH--XR,
      respectively. These findings suggested that GSH--DXR interacted with the
      substrate-binding site of the GST molecule and inhibition of GST activity
      exhibited potent cytotoxicity.

PMID- 11460003
TI  - Development of human anti-thymidine kinase antibodies.

PMID- 11460004
TI  - Intravenous magnesium does not influence the activity of the coagulation cascade.
AB  - Experimental arterial thrombus formation is reduced during intravenous magnesium
      infusion. It is well documented that magnesium reduces platelet reactivity, but
      the antithrombotic effect could also originate from anticoagulant properties or
      increased fibrinolysis. We therefore evaluated the effect of intravenous
      magnesium on prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III
      complex (TAT) concentrations, and fibrin degradation products (FbDP) in a
      randomized, cross-over study in 14 healthy volunteers. Citrated blood samples
      were collected at 0, 30, and 180 min. An additional in vitro study on magnesium's
      effect on the activity of different coagulation factors was carried out. A
      transient increase was seen in F1 + 2 and TAT after 30 min but without any
      significant difference between the placebo and magnesium period. FbDP did not
      change significantly between the two treatments. Increasing concentrations of
      magnesium dose-dependently decreased binding of activated factor X to activated
      factor VII (FVIIa), but the decrease was slight and probably without any
      significance for coagulation at the concentrations tested. No effect was observed
      on the activity of FVIIa or activated factor VIII. In conclusion, no significant
      differences were observed on markers of coagulation or fibrinolytic activity
      during intravenous magnesium infusion. These results indicate that the observed
      antithrombotic effect of magnesium is more likely to arise from the previously
      observed platelet inhibition.

PMID- 11460005
TI  - Stability of coagulation proteins in frozen plasma.
AB  - This study reports on the frozen stability of all commonly measured coagulation
      proteins in normal citrated plasma: activated partial thromboplastin time,
      prothrombin time (%), thrombin time and fibrinogen (Clauss); clotting assays for
      factors II, V, VII, VIII, IX, X, XI and XII; functional assays for protein C
      (clotting), protein S (clotting), antithrombin (chromogenic) and plasminogen
      (chromogenic); and immunological assays for von Willebrand factor and D-dimer.
      All these factors listed are stable for up to 3 months if frozen at -24 degrees C
      or lower. At -74 degrees C, all these factors (allowing for 10% variation) were
      stable for at least 18 months, most were stable for 24 months. The number of
      proteins showing > 5% variation over baseline after 6 months storage indicates
      that some decay does occur even at -74 degrees C. There was no clear advantage in
      snap freezing at -74 degrees C and then storing at -24 degrees C over both
      freezing and storing at -24 degrees C; therefore, the freezing process itself is
      not responsible for the loss of stability. The best stability, especially at -24
      degrees C, was obtained when small samples (1 ml) were stored in screw-cap tubes
      with a minimum dead space. The decrease in stability of the coagulation proteins
      directly correlates with the effect of temperature and time.

PMID- 11460006
TI  - Location of the platelet binding site in zymogen coagulation factor IX.
AB  - The assembly of the tenase complex on the surface of the platelet is an essential
      step in maintaining normal hemostasis as evidenced by the serious hemorrhagic
      diathesis associated with either factor IX (FIX) or factor VIII deficiencies.
      Understanding the regions and or residues of FIX crucial for proper binding to
      platelets has important clinical implications. The ability of FIX to bind
      activated platelets in the presence of 4 mmol/l CaCl2 was examined using
      electrophoretic light-scattering experiments. Wild-type FIX binds to activated
      platelets with dissociation constant Kd = 7.9 nmol/l. Activated FIX binds to
      activated platelets with Kd = 2 nmol/l. Activated factor VII does not bind
      activated platelets at physiological concentrations. The Gla domain of FIX is
      important for the binding of FIX to activated platelets since a chimera with a
      factor VII (FVII) template and FIX Gla [FVII(FIXGla)] has Kd = 9.6 nmol/l, and a
      chimera with a FVII template and FIX Gla, A and the first epidermal growth factor
      domain (EGF1) [FVII(FIXGla,A,EGF1)] has Kd = 9.7 nmol/l, but a chimera with a FIX
      template and a FVII Gla [FIX(FVIIGla)] does not bind activated platelets.
      Altering the fifth residue of FIX from a lysine to an alanine (Lys5<--Ala)
      abolishes the mutant from binding to collagen but does not affect FIX binding to
      the activated platelet (Kd = 9.8 nmol/l). Point mutations involved with residues
      4 and 5 (Gly4<--Phe and Lys5<--no residue), residue 9 (Phe9<--Ala), residue 10
      (Val10<--Lys) and residues 9-11 (Phe9<--Met, Val10<--Lys, Glu11<--Lys) do not
      bind to activated platelets.

PMID- 11460007
TI  - Fluorescent multiplex polymerase chain reaction analysis of four genes associated
      with inpaired fibrinolysis and myocardial infarction.
AB  - Multiplex polymerase chain reaction (PCR) allows for the simultaneous
      amplification of several genes, thereby optimizing the use of reagents and
      decreasing personnel time. Multiplex PCR was used to amplify four genes in one
      PCR reaction, demonstrating the advantage of multiplex PCR for our study since it
      allowed us to amplify four separate genes using only 1 microl DNA, thus
      maximizing the use of study DNA. As compared with conventional multiplex PCR
      analysis with ethidium bromide, incorporating fluorescence-labeled primers into
      multiplex PCR reactions facilitated accurate, simultaneous analysis of many DNA
      fragments within one base discrimination. We have used this fluorescence
      methodology to analyze polymorphisms associated with either impaired fibrinolysis
      or myocardial infarction. These include the angiotensin converting enzyme
      insertion/deletion (I/D) polymorphism in intron 16 of the DCP1 gene, the Alu I/D
      polymorphism of the tissue plasminogen activator-25 locus in intron 8, the
      plasminogen activator inhibitor 4G/5G repeat polymorphism, and the variable
      number tandem repeat of the endothelial cell nitric oxide synthase gene, all
      characterized by an insertion, deletion, or repeat. The amplified products were
      diluted 1 : 60 and analyzed on the ABI PRISM 310 Genetic Analyzer using GeneScan
      software. With this method, we were able to amplify four genes using 75% less
      reagents and personnel time, thus demonstrating the benefit of multiplex PCR and
      fluorescence technology.

PMID- 11460008
TI  - In vitro interaction of C1-inhibitor with thrombin.
AB  - Previous observations of increased generation of thrombin during acute attacks of
      angioedema in plasma of patients with C1-inhibitor (C1-INH) deficiency prompted
      us to evaluate the interaction of C1-INH with thrombin in both purified systems
      and human plasma. For this purpose, we used several methods: (1) sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis; (2)
      enzyme-linked immunosorbent assays to measure complexes between C1-INH and
      thrombin and inactivated C1-INH; and (3) kinetic studies using a chromogenic
      assay. We found that the interaction of purified C1-INH with thrombin is
      associated with the formation of bimolecular complexes of molecular weight (Mr)
      130 000 and 120 000 as well as with the appearance of a cleaved form of C1-INH of
      Mr 97 000. The kinetic studies of inhibition of thrombin by C1-INH showed an
      average second-order rate constant of 19/s per mol/l, which was significantly
      increased in the presence of heparin. The addition of thrombin to human plasma
      was not associated with detectable C1-INH-thrombin complex formation or with
      cleavage of C1-INH. In conclusion, our data demonstrate that C1-INH upon
      interaction with thrombin, in part, forms enzyme-inhibitor complexes and, in
      part, is cleaved. The low second-order rate constant and the lack of a
      significant interaction in plasma suggest that the inhibition of thrombin by C1
      INH has a minor role in circulating blood; however, its role might be important
      at the endothelial surface, where high concentrations of glycosaminoglycans
      occur.

PMID- 11460009
TI  - Maximal endothelial tissue plasminogen activator release is not impaired in
      patients with acute coronary syndromes before heparin treatment.
AB  - Procoagulant and fibrinolytic disturbances are described in patients with acute
      coronary syndromes (ACS), but whether defective maximal tissue plasminogen
      activator (t-PA) release from the endothelium is also present is still
      controversial. Previous studies did not take into consideration the contribution
      of heparin, which strongly affects fibrinolysis. Accordingly, in this study, we
      measured maximal t-PA release in patients with ACS before, during, and after
      heparin treatment. Maximal t-PA release was measured by the venous occlusion test
      in 38 hospitalized patients with confirmed ACS (18 acute myocardial infarctions
      and 20 unstable anginas) before starting heparin, during heparin treatment, and 4
      and 12 h after discontinuation. Plasma plasminogen activator inhibitor type 1
      (PAI-1), D-dimer and prothrombin fragment F1 + 2 were also measured. Eighteen age
      matched subjects with no evidence of coronary disease were used as controls. At
      admission, patients showed significantly higher plasma levels of t-PA, PAI-1, and
      F1 + 2 than controls. Before heparin, maximal t-PA release was similar in
      patients and controls. Heparin treatment was associated with a significant
      increase of plasma t-PA, while it did not affect maximal t-PA release.
      Coagulative and fibrinolytic disturbances are present in patients with ACS, but
      these do not include maximal t-PA release. Among our patients, maximal t-PA
      release appears stable over time and is not affected by heparin treatment.

PMID- 11460010
TI  - Changes in the extrinsic and intrinsic coagulation pathways in humans after
      decompression following saturation diving.
AB  - We have investigated the effect of simulated saturation diving on the activation
      of intrinsic and extrinsic coagulation pathways. Thirty-one male divers divided
      into two groups were tested in decompression habitat LSH-200. The first group of
      16 divers was subjected to hyperbaric exposure at pressure of 180 kPa with air as
      a breathing mixture, and the second group of 15 divers, exposed to a pressure of
      400 kPa with a heliox breathing mixture (helium-oxygen mixture: pO2, 40 kPa; pN2,
      40 kPa; pHe, 420 kPa). The concentrations of tissue factor, tissue factor pathway
      inhibitor, factors XII, X, VII, and I, prothrombin fragment F1 + 2, and thrombin
      antithrombin complex as well as platelet count, prothrombin time, activated
      partial thromboplastin time, plasmin-antiplasmin complex (PAP) and D-dimers were
      measured. We did not detect activation of the extrinsic coagulation pathway after
      decompression. There was a statistically significant decrease in platelet counts
      and factor I, XII and X concentrations after air-diving, and a potent and
      statistically significant increase of PAP concentration in both groups of divers.
      We suggest that saturated air or heliox diving followed by decompression have
      little if any effect on thrombin generation. Saturated air diving, however, may
      induce a decrease in platelet count and factor XII concentration. The observed
      elevation of PAP concentrations in both groups of divers suggests possible
      activation of fibrinolysis. The exact effect of diving and decompression on
      fibrinolytic system has to be further investigated.

PMID- 11460011
TI  - Depressed plasma activity of plasminogen or alpha2 plasmin inhibitor is not due
      to consumption coagulopathy in septic patients with disseminated intravascular
      coagulation.
AB  - We have attempted to determine whether depressed plasma plasminogen and alpha2
      plasmin inhibitor (or alpha2 antiplasmin) activity is, as a result of consumption
      coagulopathy, a specific finding of disseminated intravascular coagulation (DIC)
      in septic patients. The hemostatic parameters of 139 septic patients (68 with DIC
      and 71 without DIC) were analyzed. Among the group as a whole, plasma activities
      of plasminogen and alpha2 plasmin inhibitor were significantly depressed in
      septic patients with DIC relative to those without DIC (P < 0.01 and P < 0.05,
      respectively). Notably, a significant correlation was observed between plasma
      levels of albumin and plasminogen activity, as well as between plasma levels of
      albumin and alpha2 plasmin inhibitor activity both in septic patients with DIC
      and those without DIC. However, no significant correlation was observed between
      plasma levels of plasmin-alpha2 plasmin inhibitor complex (PIC) and plasminogen
      activity, nor between PIC and alpha2 plasmin inhibitor activity either in septic
      patients with DIC or those without DIC. We concluded that depressed activity of
      plasminogen or alpha2 plasmin inhibitor is not as a result of consumption
      coagulopathy, but rather a result of low synthetic function of the liver in
      septic patients with DIC.

PMID- 11460012
TI  - Thrombogenic alleles, Escherichia coli O157:H7 infections, and hemolytic uremic
      syndrome.
AB  - Hemolytic uremic syndrome (HUS) of childhood most commonly follows
      gastrointestinal infection with Escherichia coli O157:H7. This pathogen
      elaborates Shiga toxins that are believed to cause microvascular injury and to
      trigger a thrombogenic response. The exact mechanisms leading to variable disease
      manifestations are unknown. Allelic variation in genes encoding selected
      coagulation factors and inhibitors of fibrinolysis were examined to determine
      whether or not a causal relationship exists between hypercoagulability and the
      development of HUS. No correlation between the thrombogenic factor V (G1691A),
      factor II (G20210A), methylenetetrahydrofolate reductase (C677T), or the
      plasminogen activator inhibitor (PAI)-1 promotor (4G/5G) genotypes and the risk
      of infection with E. coli O157:H7, or the risk of development of HUS among
      infected patients, was found. Serum PAI-1 levels did not correlate with the PAI-1
      genotype. We conclude that the alleles studied are not major risk factors for the
      acquisition of E. coli O157:H7 infection, or of E. coli O157:H7-related HUS.

PMID- 11460013
TI  - In vitro factor XI activation mechanism according to an optimized model of
      activated partial thromboplastin time test.
AB  - Whether the in vitro activation of factor XI in plasma is mediated by thrombin or
      by auto-activation remains a controversial question. In this context, we have
      simulated theoretical activated partial thromboplastin time (aPTT) by means of a
      program based on a body of 22 essential elementary reactions implemented with
      rate constants quoted in current literature. To meet self-consistency in input
      data issued from varying sources, the results were optimized using the simplex
      treatment. The performance of the model was systematically evaluated considering
      the extent of the deviations observed between predicted aPTT and laboratory
      measurements conducted on normal and factor VIII, IX, XI and XII single-factor
      deficient plasma. The influence of the auto-activation or thrombin-mediated
      activation of factor XI on these aPTTs was tested separately after insertion of
      these reactions in the model. According to the best fits, a mechanism accounting
      for an auto-activation reaction of activated factor XI rather than a positive
      feedback reaction mediated by thrombin seemed more likely. Based on this
      conclusion, a chart of self-consistent rate constant values accounting for the
      intrinsic pathway of coagulation under static conditions is proposed.

PMID- 11460014
TI  - All-trans retinoic acid is partially effective against lipopolysaccharide-induced
      but not against tissue-factor-induced disseminated intravascular coagulation in
      rat models.
AB  - All-trans retinoic acid (ATRA) has been introduced to the management of acute
      promyelocytic leukemia (APL) as a differentiation treatment. This drug not only
      causes complete remission, but also improves disseminated intravascular
      coagulation (DIC) without adding anticoagulants in APL. We have attempted to
      determine whether ATRA is effective against DIC in rat models induced by tissue
      factor (TF) or lipopolysaccharide (LPS), because the anticoagulant effect of ATRA
      has been considered to induce thrombomodulin upregulation and TF downregulation
      on endothelial cells as well as on APL cells. In male Wistar rats, DIC was
      induced by a 4-h infusion of thromboplastin (3.75 U/kg) or lipopolysaccharide (30
      mg/kg). The rats were given ATRA orally each day at a dose of 100 mg/kg per day
      for 1 week before the injection of TF or LPS in ATRA treatment groups, or given
      low molecular weight heparin (LMWH) 10 min before the injection of TF or LPS (200
      U/kg, bolus intravenously) in LMWH treatment groups. No significant changes in
      hemostatic parameters or markers of organ dysfunction were caused by the ATRA
      administration, while DIC was significantly improved by LMWH in the TF-induced
      model. DIC was significantly improved by both ATRA and LMWH in the LPS-induced
      model. These findings suggested that ATRA was useful for treating DIC only in the
      LPS-induced model, and that drug efficacy should be carefully assessed because
      the agents used to induce DIC considerably influenced the outcome.

PMID- 11460015
TI  - Abnormal haemorheology, endothelial function and thrombogenesis in relation to
      hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke
      Project.
AB  - While the blood vessels are exposed to high pressures in hypertension, the main
      complications of hypertension (stroke and myocardial infarction) are
      paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities
      of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von
      Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis
      (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of
      concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female)
      aged < 75 years (mean age +/- SD, 64.2 +/- 9.2 years) with acute stroke (ictus <
      12 h). Baseline blood tests on admission were compared with 46 'hospital
      controls' (patients with uncomplicated essential hypertension; mean age +/- SD,
      65.9 +/- 3.8 years) and 24 healthy normotensive controls (mean age +/- SD, 65 +/-
      14.0 years). Further comparisons were made between stroke patients with
      hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 90 mmHg) on
      admission and those without hypertension. Mean plasma viscosity (one-way analysis
      of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly
      higher in stroke patients and hospital controls, when compared with healthy
      controls. The von Willebrand factor, plasminogen activator inhibitor soluble P
      selectin and fibrin D-dimer levels were highest in the acute stroke patients,
      intermediate in hospital controls and lowest in healthy controls (all P < or =
      0.001). There were no significant differences in measured indices of
      haemorheology, endothelial dysfunction and thrombogenesis between the three
      stroke pathological subtypes (ischaemic/thrombotic, haemorrhagic or transient
      ischaemic attack). There were also no significant differences in the measured
      parameters for stroke patients with or without systolic blood pressure > 160 mmHg
      or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean
      daytime or night-time ambulatory blood pressure monitoring recordings. There were
      no statistically significant differences between the measured parameters on
      admission and at 3 months follow-up in 26 patients (all P = not significant).
      Plasma viscosity was significantly correlated with mean daytime systolic blood
      pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r =
      0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has
      demonstrated clear abnormalities of haemorheology, endothelial dysfunction,
      platelet activation and thrombogenesis, which do not appear to be affected by the
      height of the blood pressure or the presence of hypertension. This is despite the
      known hypercoagulable state found in hypertension and the relationship of
      haemostatic abnormalities to vascular complications.

PMID- 11460016
TI  - Polymorphisms of the tissue factor pathway inhibitor gene and the risk of
      restenosis after coronary angioplasty.
AB  - Intracoronary stent implantation is associated with a significantly lower risk of
      restenosis compared with balloon angioplasty. However, restenosis still occurs in
      some cases. Experimental studies suggest that the tissue factor pathway is
      involved in this phenomenon. We investigated a possible relationship between
      three previously identified polymorphisms of the tissue factor pathway inhibitor
      (TFPI) gene and restenosis in 443 patients who underwent angioplasty, with or
      without stent implantation. The effect of the intron 7-33T<--C polymorphism and
      that of the combined intron 7 and promoter genotype on plasma TFPI levels was
      also investigated in 58 healthy subjects. DNA analysis was performed by
      polymerase chain reaction amplification of genomic DNA extracted from white blood
      cells, followed by digestion with the restriction enzymes Hind III, Nde I and Mae
      III for the detection of promoter, intron 7 and exon IX polymorphisms,
      respectively. The minimal luminal diameter, percent stenosis, acute gain, late
      loss and loss index did not differ according to the genotype before, immediately
      after or 6 months after angioplasty, regardless of stent implantation.
      Interestingly, subjects with the intron 7 CC genotype had significantly higher
      total TFPI levels than those with the TT genotype before and after an enoxaparin
      injection. Moreover, subjects with the -287TT/Int7TT combined genotype had the
      lowest plasma TFPI levels. Despite significant variations in plasma TFPI levels,
      we found no evidence that three polymorphisms of the TFPI gene influence the risk
      of restenosis. These results do not exclude the possibility that other
      polymorphisms in the TFPI gene may influence this risk.

PMID- 11460017
TI  - Liver transplant acquired activated protein C resistance presenting with deep
      vein thrombosis 4 years after transplant.

PMID- 11460018
TI  - The pig-tailed macaque rectal model: microflora and chlamydial infection.
AB  - BACKGROUND: A topical microbicide should protect against acquisition of sexually
      transmitted infection during both vaginal and rectal intercourse. The rectal
      microflora of the Macaca nemestrina (pig-tailed macaque) and humans were
      examined, as well as the histopathology of rectal tissues. In a subset of
      macaques, a human rectal isolate of Chlamydia trachomatis was inoculated into the
      rectum to establish rectal chlamydial infection. GOAL: To evaluate the
      comparability of the pig-tailed macaque rectal model with humans. STUDY DESIGN:
      Rectal swabs were collected for microbiologic analysis to characterize normal
      microflora in pig-tailed macaques and humans. Subsequently, 10 macaques received
      a rectal inoculation with C trachomatis, serovar D, prepared from a clinical
      rectal isolate. RESULTS: The rectal microflora of pig-tailed macaques (n = 80)
      were found to be comparable with the rectal flora of humans (n = 40). The
      prevalence of Lactobacillus in the rectum was higher in the macaques than in
      humans. Coliform and Enterococcus were decreased in the macaques, as compared
      with those of humans. In 9 of 10 macaques, rectal chlamydial infection was
      confirmed by culture or ligase chain reaction on days 2, 7, and 14 after
      inoculation. The test results were positive for rectal chlamydial infection by
      ligase chain reaction only for the remaining animal on day 14 after inoculation.
      CONCLUSIONS: The findings demonstrate that the rectal environment of the pig
      tailed macaque is a useful model for further evaluation of newly developed
      topical microbicides for rectal use. Furthermore, such products can be evaluated
      for protection against rectal chlamydial infection in this model.

PMID- 11460019
TI  - Healthcare-seeking behavior and sexual behavior of patients with sexually
      transmitted diseases in Nairobi, Kenya.
AB  - BACKGROUND: Sexual and health-seeking behaviors are important components of
      sexually transmitted disease (STD) control. GOALS: To generate data for improved
      STD prevention and care, and to assess sexual behavior and relevant health
      seeking behavior. STUDY DESIGN: A questionnaire to elicit social, demographic,
      healthcare-seeking, and sexual behavior information was administered to 471
      patients attending the referral clinic for STDs in Nairobi, Kenya. RESULTS: A
      large proportion of the patients had sought treatment in public and private
      sectors before attending the clinic for STDs. Women waited longer than men to
      seek medical care. In addition, women more than men engaged in sex while
      symptomatic, mostly with their regular partner. Condoms were used rarely during
      illness. In their self-reports, 68% of the men admitted to having extramarital
      affairs, and 30% to paying for sex, yet they blamed their wives for their STDs.
      CONCLUSION: Health education messages in Kenya need adaptation to improve health
      seeking behavior and safe sex practices.

PMID- 11460020
TI  - Sexually transmitted infections and reproductive health in Azerbaijan.
AB  - BACKGROUND: Little is known about the prevalence of sexually transmitted
      infections (STIs) and about sexual and reproductive health in Central and Eastern
      Europe. However, it is clear that major epidemics of STIs currently exist. GOAL:
      To provide baseline information for the development of national guidelines on the
      management of STIs in Azerbaijan. STUDY DESIGN: A prevalence study on STIs,
      including a questionnaire on sexual and reproductive health, in two regions of
      Azerbaijan targeted three groups: (1) pregnant women, (2) gynecology patients,
      and (3) men attending a dermatovenereology clinic. RESULTS: The 407 pregnant
      women in this study had a mean of 1.47 abortions and 1.40 births per woman. Of
      these women, 12% reported condom use and 41% previous symptoms of a sexually
      transmitted infection. Active syphilis was found in 1.7% of the women. The 326
      gynecology patients had a mean of 2.54 abortions and 2.63 births per woman. Of
      these patients, 11% reported use of modern contraceptives, 18.3% previous condom
      use, and 63% previous symptoms of an STI. The prevalence of active syphilis was
      2.2%, Chlamydia trachomatis 3.1%, Neisseria gonorrhoeae 2.8%, Trichomonas
      vaginalis 7.1%, Candida 33.1%, and bacterial vaginosis 32.5%. Of the 197 male
      patients, 67% reported multiple partners in the past 3 months, 62% money
      exchanged for sex, 37% condom use ever, and 40% a history of STIs. Active
      syphilis was found in 9.5% of the men, C trachomatis in 5.9%, N gonorrhoeae in
      17%, and T vaginalis in 4.4%. CONCLUSIONS: The data show high-risk behavior in
      the men attending STI clinics, poor sexual and reproductive health status in the
      women, and underreporting of official data.

PMID- 11460021
TI  - Characteristics of those who repeatedly acquire sexually transmitted infections:
      a retrospective cohort study of attendees at three urban sexually transmitted
      disease clinics in England.
AB  - BACKGROUND: Individuals who repeatedly acquire sexually transmitted infections
      (STIs) may facilitate the persistence of disease at endemic levels. Identifying
      those most likely to become reinfected with an STI would help in the development
      of targeted interventions. GOAL: To investigate the demographic and behavior
      characteristics of sexually transmitted disease (STD) clinic patients most likely
      to reattend with an STI. STUDY DESIGN: The proportion of patients attending three
      STD clinics in England between 1994 and 1998 who reattended for treatment of
      acute STI within 1 year was estimated from Kaplan-Meier failure curves. A Cox
      proportional hazard model was used to investigate the relation between rate of
      reattendance with an acute STI and patient characteristics. RESULTS: Of the
      17,466 patients presenting at an STD clinic with an acute STI, 14% reattended for
      treatment of an STI within 1 year. Important determinants of reinfection were
      age, sexual orientation, and ethnicity: 20% of 12- to 15-year-old females
      (adjusted hazard ratio [HR], 1.90; CI, 1.13-3.18, compared with 20- to 24-year
      old females), 22% of homosexual men (adjusted HR, 1.30; CI, 1.07-1.58, compared
      with heterosexual men), and 25% of black Caribbean attendees (adjusted HR, 1.87;
      CI, 1.63-2.13, compared with whites) reattended for treatment of acute STI within
      1 year. In addition, 21% of those with a history of STI (adjusted HR, 1.42; CI,
      1.28-1.59, compared with those with no history of STI) and 17% of individuals
      reporting three or more partners in the recent past (adjusted HR, 1.53; CI, 1.34
      1.73, compared with those with one partner) reattended for treatment of an acute
      STI within 1 year. CONCLUSIONS: In this STD clinic population, teenage females,
      homosexual men, black Caribbean attendees, individuals with a history of STI, and
      those reporting high rates of sexual partner change repeatedly re-presented with
      acute STIs. Directing enhanced STD clinic-based interventions at these groups may
      be an effective strategy for STI control.

PMID- 11460022
TI  - Psychosocial factors associated with self-reported male condom use among women
      attending public health clinics.
AB  - BACKGROUND: Previous research has identified factors associated with condom use.
      However, less information exists on the impact that a history of sexually
      transmitted disease (STD) has on condom use. GOAL: To identify factors associated
      with self-reported male condom use that relate to a history of STD. STUDY DESIGN:
      Women attending STD clinics completed a survey that assessed sexual behavior, STD
      history, and psychosocial characteristics. Binomial regression was used to
      estimate the association between these factors and condom use. RESULTS: Of the 12
      factors included in the regression model, 11 were significant for all women. When
      the analysis was stratified by STD history, high condom use self-efficacy, high
      convenience of condom use, and high frequency of condom use requests were
      significantly associated with increased condom use among women with or without a
      history of STD. Factors such as greater perceived condom use norms, higher
      perceived level of risk, and greater need for condom use in long-term
      relationships were significantly associated with increased condom use among women
      with a history of STD. Factors such as shorter duration of a relationship, less
      violence in the relationship, and lifetime drug use were associated with
      increased condom use among women with no history of STD. CONCLUSIONS: The pattern
      of psychosocial factors determining condom use is modified by a positive history
      of STD. These findings suggest that a history of STD could be an important factor
      in targeting condom use interventions.

PMID- 11460023
TI  - Evaluation of a low-dose nonoxynol-9 gel for the prevention of sexually
      transmitted diseases: a randomized clinical trial.
AB  - BACKGROUND: Low-dose nonoxynol-9 products have a potential advantage of reduced
      toxicity. However, little is known about their efficacy in reducing the incidence
      of sexually transmitted diseases (STDs). GOAL: To determine the effect that an
      intravaginal gel containing 52.5 mg of nonoxynol-9 has on the acquisition of STDs
      in a cohort of HIV-1-seronegative female sex workers in Mombasa, Kenya. STUDY
      DESIGN: A randomized double-blind placebo controlled trial was performed.
      RESULTS: In this study, 139 women were randomized to the nonoxynol-9 group and
      139 to the placebo group. No significant differences were found between the two
      study groups in terms of safety outcomes and reported symptoms, except for a
      lower incidence of vaginal erythema in the nonoxynol-9 group. There was a
      significantly higher incidence of gonorrhea in the nonoxynol-9 group than in the
      placebo group. No significant differences were observed between the groups for
      acquisition of Candida, trichomonas, bacterial vaginosis, C trachomatis,
      syphilis, or HIV-1, although the statistical power to detect differences for some
      of these STDs was limited. CONCLUSIONS: In this randomized placebo-controlled
      trial of a low-dose nonoxynol-9 gel, a significantly higher incidence of
      gonorrhea was found in the nonoxynol-9 group, but no significant differences
      between the groups were found for Candida, trichomonas, bacterial vaginosis, C
      trachomatis, syphilis, or HIV-1.

PMID- 11460024
TI  - The proportion and characteristics of adolescents who return for anonymous HIV
      test results.
AB  - BACKGROUND: The proportion of adolescents who return for HIV test results varies
      widely, and knowledge of what characteristics affect their return is limited.
      GOAL: To quantify the proportion of adolescents who return for results of
      anonymous HIV tests, and to identify the characteristics that predict their
      return. STUDY DESIGN: This retrospective study evaluated 285 adolescents
      consenting to anonymous HIV tests in an urban clinic that provides medical
      services free of charge without eligibility requirements to a mostly working,
      uninsured population. RESULTS: Of the adolescents studied, 42% returned for test
      results. Three characteristics independently predicted their return: (1) coming
      to the clinic only for HIV testing, (2) having private health insurance, and (3)
      engaging in unprotected sex while using drugs or alcohol. CONCLUSIONS: Except for
      having unprotected sex while using drugs or alcohol, the characteristics that
      placed adolescents at risk for HIV infection did not predict their return for
      test results. Given the low return rate for anonymous testing in this setting,
      confidential testing, which permits follow-up evaluation of those failing to
      return for test results, should be considered.

PMID- 11460025
TI  - HIV infection among foreign transsexual sex workers in Rome: prevalence, behavior
      patterns, and seroconversion rates.
AB  - BACKGROUND: The Azienda Sanitaria Locale Roma E (ASL-RME) outpatient clinic is
      the main reference center in Rome for HIV testing of foreign people. GOAL: To
      define the prevalence and incidence of HIV infection among foreign transsexual
      sex workers attending the center. STUDY DESIGN: A cross-sectional, follow-up
      study was conducted. RESULTS: Between 1993 and 1999, 353 transsexuals attended
      the ASL-RME. They were from Colombia (n = 208), Brazil (n = 122), and other
      countries (n = 23). Most of these transsexuals reported having 5 to 10 partners
      per day. The overall HIV prevalence was 38.2%, which multivariate analysis found
      to be associated with origin from Brazil and a higher number of sex partners. The
      observed HIV seroconversion rate was 4.1 per 100 person-years, and non-regular
      condom use was the only factor related to seroconversion. CONCLUSIONS: The data
      from this study suggest that promotion of safer sex practices and regular condom
      use still is the main priority among marginalized population subgroups, such as
      foreign prostitutes, involved in sex activities that put them at risk for HIV
      infection.

PMID- 11460026
TI  - Congenital syphilis and fluorescent treponemal antibody test reactivity after the
      age of 1 year.
AB  - BACKGROUND: Many believe that a persistently reactive fluorescent treponemal
      antibody absorption (FTA-ABS) is manifested with congenital syphilis after the
      age of 1 year, that it is useful in the retrospective diagnosis of children with
      congenital syphilis, and that it can be used to confirm other treponemal tests.
      GOAL: To determine whether a reactive FTA-ABS after the age of 12 months is
      indicative of congenital syphilis. STUDY DESIGN: Prospective outpatient follow-up
      evaluation until at least the age of 12 months was conducted for 194 babies born
      to mothers with reactive syphilis serology at delivery, and for two additional
      children with congenital syphilis diagnosed when they were younger than 1 year
      (total, 196 children). RESULTS: In the study group, 54 children had reactive FTA
      ABS (reactors) until the age of at least 12 months or more, and 142 children had
      nonreactive FTA-ABS (nonreactors) at the age of 12 months or more. Of the 54
      reactors, 17 (31%) had evidence of congenital syphilis at birth, whereas evidence
      of congenital syphilis was seen in 14 of the 142 (10%) nonreactors (P = 0.0002).
      At 15 months, nonreactive FTA-ABS developed in six reactors, and eventually in 15
      of 44 reactors (34%) tested. CONCLUSIONS: A reactive FTA-ABS may be seen at 12
      months in children with and without evidence of congenital syphilis at birth. Not
      all children with congenital syphilis will manifest reactive FTA-ABS at 12
      months, and FTA-ABS reactivity wanes with time.

PMID- 11460027
TI  - Tests of Buffergel for contraception and prevention of sexually transmitted
      diseases in animal models.
AB  - BACKGROUND: BufferGel is a novel spermicidal and microbicidal gel formulated to
      maintain the natural protective acidity of the vagina by acidifying semen, which
      otherwise alkalinizes the vagina. GOAL: To test the efficacy of BufferGel for
      preventing sexually transmitted infections and pregnancy in animal models. STUDY
      DESIGN: Animals were challenged with pathogens or sperm after pretreatment with
      both test and control agents, or after no pretreatment, then evaluated for
      infection or pregnancy using standard methods. RESULTS: BufferGel provided
      significant contraceptive efficacy in the rabbit, and significant protection
      against vaginal and rectal transmission of herpes simplex virus type 2 (HSV-2) in
      the mouse, vaginal transmission of Chlamydia trachomatis in the mouse, and skin
      transmission of cottontail rabbit papillomavirus in the rabbit. It did not
      protect against vaginal transmission of Neisseria gonorrhoeae in the mouse.
      CONCLUSIONS: The protective efficacy of BufferGel in five of the six animal
      models suggests that this microbicide warrants clinical evaluation for both
      contraception and disease prevention.

PMID- 11460028
TI  - Antenatal seroprevalence of herpes simplex virus type 2 (HSV-2) in Canadian
      women: HSV-2 prevalence increases throughout the reproductive years.
AB  - BACKGROUND: This study sought to provide the first population estimates of herpes
      simplex type 2 (HSV-2) seroprevalence in Canada. GOAL: To measure the antenatal
      seroprevalence of HSV-2 antibodies in reproductive age women. STUDY DESIGN: An
      anonymous unlinked seroprevalence study used stored sera collected from pregnant
      women in British Columbia during 1999. Randomized sampling within age strata
      selected a total of 1215 subjects, ages 15 to 44 years. Serologic testing used
      the Gull Meridian Test. Overall prevalence was directly standardized to the 1999
      Canadian female population. RESULTS: The age-adjusted prevalence for HSV-2 was
      17.3% (95% CI, 15.2-19.4). Prevalence ranged from 7.1% (ages, 15-19 years) to
      28.1% (ages, 40-44 years), with the largest increases after the age of 24 years.
      CONCLUSIONS: The HSV-2 seroprevalence among pregnant women in British Columbia is
      similar to that in the United States and other countries. Seroprevalence
      continues to rise through the later reproductive years. This observation may
      relate to continued transmission, an age cohort effect, or both.

PMID- 11460031
TI  - [Immunotherapy for melanoma: how can tolerance be overcome?].

PMID- 11460032
TI  - [Oncogenic human papillomaviruses in extra-genital Bowen disease revealed by in
      situ hybridization].
AB  - BACKGROUND: The association between mucosal oncogenic human papillomaviruses
      (HPV) and bowenoid papulosis or genital Bowen's disease is well documented. In
      contrast this association with extra-genital Bowen's disease is poorly studied.
      The aim of this study was to detect oncogenic (16/18, 31/33/51) and non oncogenic
      (8/11) mucosal HPV using a in situ hybridization method in 28 skin biopsy
      specimens of extra-genital Bowen's disease. PATIENTS AND METHODS: Twenty-eight
      cases of extra-genital Bowen's disease seen in the period 1990-96 in the
      Dermatology department were included: 19 women and 9 men (mean age: 72 years).
      Bowen's disease locations were: hands and feet (8 cases), limbs (11 cases), face
      (8 cases), trunk (1 case). Blinded histopathologic examination confirmed the
      diagnosis of Bowen's disease and signs of HPV infection (koilocytosis). In situ
      hybridization was performed using three biotinylated probes detecting HPV types
      6/11, 16/18, 31/33/51. RESULTS: Oncogenic HPV genoma was detected in 8 skin
      samples (28.6 p. 100). In all these cases, 16/18 probe was positive and in two
      cases, both 16/18 and 31/33/51 probes were positive; 4/8 Bowen's diseases of the
      extremities were positive for HPV. Koilocytes were found in 6/8 of skin samples
      with positive HPV detection. DISCUSSION: Mucosal oncogenic HPV are detected by in
      situ hybridization in 28.6 p. 100 of extra-genital Bowen's disease. In situ
      hybridization is an easier technique than Southern-Blot hybridization which is
      the gold standard. Five studies reported similar results and three studies
      reported different results that we discuss. A precise understanding of oncogenic
      HPV implication in the development of extra-genital Bowen's disease could lead to
      the development of new therapeutic strategies (topical cidofovir or imiquimod).

PMID- 11460033
TI  - [Depigmentation for cosmetic purposes: prevalence and side-effects in a female
      population in Senegal].
AB  - BACKGROUND: Use of depigmenting agents by black women for cosmetic purposes is a
      long-standing practice. Most depigmenting agents contain topical steroids and
      hydroquinone. The purpose of this study was to clarify prevalence data on use of
      depigmenting agents in a female population in Senegal and to report the incidence
      and main features of adverse skin reactions in addition to possible associations
      with diabetes, hypertension and renal insufficiency. PATIENTS AND METHODS: A
      cross-sectional study was made in a representative sample of 147 hospitalized
      women aged from 15 to 60 years. The incidence of adverse skin reactions,
      diabetes, hypertension and serum creatinine in 41 women admitting use of
      depigmenting agents was compared to those found in 85 women who maintained they
      had never used depigmenting agents. Two patients who refused to participate in
      the study and 19 others who did use depigmenting products and had stopped their
      use for at least 3 months were excluded from the analysis. RESULTS: The
      prevalence of use of depigmenting agents was 27.9% (47/147). Adverse skin
      reactions were significantly more frequent among these patients. Effects observed
      were similar to those reported for prolonged use of topical steroids but also
      included periorbitary dyschromia, exogenous ochronosis, infectious dermatosis,
      and, in particular, extended dermatophytosis and necrotizing cellulitis, contact
      eczema, and certain hyperpigmentation when depigmenting agents were discontinued.
      Presence of relative hyperpigmentation of the dorsal phalanges identified use of
      depigmenting agents with a 100% specificity. Prevalence of diabetes and
      hypertension was significantly higher among the group of women using depigmenting
      agents (46.3% and 8.2%, versus 34.1% and 8.2% respectively). There was no
      difference for renal insufficiency. The risk increased independently of age
      depending on whether duration of use was less than 10 years or not with a
      relative risk that rose from 3.63 (1.2-10.47) to 6.47 (3.41-12.32) for diabetes
      and from 1.34 (0.45-3.96) to 2.65 (1.27-5.51) for hypertension, clearly
      suggesting a possible dose effect. DISCUSSION: The prevalence of use of
      depigmenting agents in this first published hospital series confirms the
      widespread nature of this phenomenon in Senegal. While certain patent skin signs
      are similar to those described in the literature, and excluding specific features
      related to the hospital setting, this is the first report of a dose-effect
      between use of depigmentation agents and diabetes and hypertension, probably via
      the effect of topical steroids.

PMID- 11460034
TI  - [Tinea capitis: sample surveys among school doctors and dermatologists in the
      Paris suburbs].
AB  - BACKGROUND: Subsequent to detection of several cases of anthropophilic tinea
      capitis, we wanted to know whether the legal decree requiring eviction from
      school and an epidemiology survey in the children community or the family is
      implemented properly. METHODS: Two sample surveys were carried out among 50
      school doctors from the Hauts-de-Seine department and 110 dermatologists working
      the Paris suburbs. RESULTS: Eviction from school was rare and not based on the
      type of dermatophytes (anthropophilic or zoophilic agent). Likewise, epidemiology
      survey was neglected, often being solely clinical for other family members.
      Systematic sampling in the children community or in the family was very
      exceptional. DISCUSSION: Despite the rise in the number of cases of
      anthropophilic tinea capitis in Paris suburbs, the decree is not often
      implemented. Dermatologists would appear to be responsible for this situation,
      especially in case of M. langeronii, which is very contagious in nursery school.

PMID- 11460035
TI  - [Photodermatosis induced by hydroxychloroquine: 4 cases].
AB  - BACKGROUND: Hydroxychloroquine is an antimalarial drug often used in dermatology
      for its photo-protective effects. Four cases of photodermatosis induced by
      hydroxychloroquine are reported. CASE REPORTS: Four patients, aged from 21 to 68
      years, developed a photolocalized eruption from 6 days to 10 weeks after starting
      hydroxychloroquine. The minimal erythemal dose was decreased in the total spectra
      and UVA at the onset of the eruption and became normal after stopping
      hydroxychloroquine in the 2 patients that were controlled. In 3 cases,
      hydroxychloroquine was the only single drug imputable; chronological imputability
      was plausible. In the last case, both hydroxychloroquine, carbamazepine and
      fluvoxamine had a common imputability which was plausible. In the 4 cases, a
      favourable outcome was observed after stopping hydroxychloroquine, and no
      recurrence occurred with a mean follow-up of 3.8 years (1-4 years). In one case,
      a photodistributed eruption occurred during treatment with a related molecule:
      chloroquine. DISCUSSION: Photodermatosis with hydroxychloroquine have rarely been
      described in the literature, while quinine from which hydroxychloroquine is
      derived, is well known for its risk of photosensibilization. The main
      differential diagnosis of these drug eruptions is an eruption caused by the
      photodermatosis that initially required treatment with hydroxychloroquine.

PMID- 11460036
TI  - [Onychomycosis in Tunis area: epidemiological and mycological data].
AB  - BACKGROUND: Onychomycosis is by far the most frequent cause of nail disease. We
      describe epidemiological and mycological features observed in the Tunis area in
      Tunisia. MATERIAL AND METHODS: Data were collected from 292 nail samples
      performed in 255 patients with suspected onychomycosis. RESULTS: Request for
      samples were made late, on the average 48 months after development of nail
      disorders. Most of the patients were women (63.5%). One hundred ninety-six
      samples were positive (67%), 130 from toe nails and 66 from finger nails.
      Simultaneous infections of both finger and toe nails were found in 22 cases.
      Associated onychomycosis and skin mycosis was found preferentially in feet
      onychomycosis. The sensitivities of direct examination and culture depended on
      the site of the onychomycosis. Cultures were more sensitive for hands where
      yeasts, particularly Candida albicans, predominated, but the direct examination
      was more sensitive for feet where dermatophytes, particularly Trichophyton
      rubrum, predominated. CONCLUSION: Mycological examination is compulsory for
      confirmation of onychomycosis. It is also recommended before initiating a costly
      long-term treatment.

PMID- 11460037
TI  - [Acitretine].
AB  - Acitretin (Soriatane(R)) is an aromatic retinoid (carboxylic acid metabolite of
      etretinate). Acitretin has a terminal elimination half-life of about 55 to 60
      hours. However, concomitant intake of alcohol induces transformation to
      etretinate (lipophilic ester) which has a longer terminal elimination half life
      (84 to 168 days). Due to the teratogenic effect of acitretin, contraception
      should be used during therapy and 2 years afterwards. Acitretin monotherapy is
      effective in pustular psoriasis and psoriatic palmo-plantar keratoderma. In the
      other forms of psoriasis, combination with phototherapy (PUVA, UVB) or topical
      therapy is necessary (calcipotriol, corticosteroids). Acitretin is effective in
      cutaneous disorders of keratinization (ichtyosis, palmo-plantar keratoderma,
      Darier's disease). Severe cutaneous forms of lichen planus were recently
      recognized as indications of acitretin treatment; 35 to 40 mg daily is the mean
      effective dosage in adults (0.5 mg/kg/j in children). Acitretin was shown
      effective in preventing the development of new skin carcinomas in predisposed
      patients (Xeroderma pigmentosum, immunosupression). Acitretin is a potent
      teratogen. Mucocutaneous side effects are varied (cheilitis, dry mucosae,
      xerosis, palmo-plantar peeling, hair loss.), dose-dependent and reversible.
      Biological side-effects consist principally in elevations of transaminases (5 to
      8% of patients). Acute hepatotoxic reactions are rare. Hyperlipidemia is another
      side-effect commonly observed. Bony changes (ligament calcifications,
      osteoporosis) have been reported with various incidence. In children, growth and
      development have to be monitored. Combination of acitretin with potentially
      hepatotoxic molecules (methotrexate) is contraindicated, as is combination with
      cyclines (risk of intracranial hypertension).

PMID- 11460038
TI  - [Efficacy of cidofovir in an HIV infected patient with an acyclovir and foscarnet
      resistant herpes simplex virus infection].
AB  - BACKGROUND: We report the case of an AIDS patient, whose persistant HSV2
      ulceration was clinically and phenotypically resistant to acyclovir and
      foscarnet. Only five clinical isolates of simultaneous acyclovir and foscarnet
      resistance have been previously described. CASE REPORT: This patient, without
      history of opportunistic infection, was hospitalized for a recurrent scrotal
      ulceration resistant to several antiviral treatment such as acyclovir,
      valacyclovir or foscarnet. The CD4 count was stable at 150/mm(3) and the HIV
      viral load was below detection level. The last recurrence appeared rapidly under
      valacyclovir therapy which had been introduced after 65 days of foscarnet
      therapy. Thus, the patient received a new dose of foscarnet. After initial
      efficacy, the ulceration increased once again. HSV2 phenotypic determination was
      done and detected, at that time, a double resistance to acyclovir and foscarnet.
      Healing was obtained with intravenous cidofovir. DISCUSSION: Foscarnet and
      acyclovir resistance in an HSV2 isolate is rare. This report presents several
      particularities. First, whereas the earlier published patients with an acyclovir
      and foscarnet resistant strain were widely immunocompromised, this was not the
      case for our patient. Secondly, in contrast with most precedent observations in
      which acyclovir-resistant strain disappeared after foscarnet therapy, in our case
      the acyclovir resistant strain remained after foscarnet therapy. Finally, few
      reports concerned the clinical efficacy of cidofovir in HSV infection. In this
      case, we proved that intravenously cidofovir was highly and rapidly effective on
      acyclovir and foscarnet resistant strains.

PMID- 11460039
TI  - [Vibratory angioedema].
AB  - BACKGROUND: Vibratory angioedema is a rare form of physical urticaria. This
      entity can be an hereditary autosomal dominant disorder or an acquired sporadic
      disease. Immediate and delayed forms have been reported. CASE-REPORT: A 34-year
      old woman was referred to us for a vibratory angioedema induced by mountain
      biking. Despite her handicap, she could provoke a clinical tolerance with
      disappearance of pruritus but not of erythema and edema if she continued her
      physical effort. Diagnosis was confirmed with a vibratory stimulus using a Vortex
      for 5 minutes. The realization of a controlled vibratory stimuli among 20
      volunteers induced a positive response in 7 cases (35 p. 100). DISCUSSION: These
      results raise the problem of the specificity of the test but also point out the
      possible physiological response of the body to intense vibratory stimulations.

PMID- 11460040
TI  - [Skin location of multiple myeloma mimicking a vascular tumor].
AB  - INTRODUCTION: Cutaneous location of multiple myeloma is rare, and generally
      develops as a consequence of direct spread from an underlying bony focus of the
      disease. Metastatic skin lesions without adjacent bone involvement are uncommon.
      The prognosis is very poor. CASE REPORT: A 74-year-old man consulted for a
      hemorrhagic cutaneous nodule localized on the left inguinal area. This patient
      had been treated for five months for a stage I IgG lambda multiple myeloma. The
      histopathologic examination of the lesion showed a predominantly nodular
      configuration made up of masses of atypical cells with numerous hemorrhagic
      areas. The diagnosis of cutaneous metastasis of multiple myeloma was confirmed by
      the positivity of the cells for anti-IgG lambda antibodies. DISCUSSION: Cutaneous
      involvement in multiple myeloma without extension from underlying bony focus is
      exceptional. The lesions generally consist of firm, erythematous nodules
      involving the neck and lower extremities. To our knowledge, we present here the
      first case mimicking clinically and histologically a malignant vascular
      proliferation.

PMID- 11460041
TI  - [Panniculitis induced by MINE chemotherapy].
AB  - BACKGROUND: Drug-induced panniculitis are uncommon. We report the second case of
      panniculitis induced by MINE chemotherapy. CASE REPORT: A 31-year-old woman with
      relapsed Hodgkin disease was treated with MINE cytostatic regimen. Multiple
      erythematous and painful nodules of panniculitis developed on her chest, abdomen
      and thighs fifteen days after the beginning of drug administration with a second
      flare up after second administration of the same drugs. The eruption cleared
      slowly after treatment withdrawal. DISCUSSION: To our knowledge, our case is the
      second reported case of panniculitis induced by MINE chemotherapy. Drug-induced
      panniculitis is uncommon and usually induced by steroid treatment. Some cases of
      panniculitis induced by atenolol, potassium bromide, apomorphine, interferon
      alpha and interleukin 2 have been described. Few cutaneous adverse effects are
      reported with MINE chemotherapy: rash, erythema and swelling of extremities. A
      case of inflammatory swelling of thighs with hemorrhagic panniculitis due to this
      treatment has been described recently.

PMID- 11460042
TI  - [Cutaneous adverse effects during selective serotonin reuptake inhibitors
      therapy: 2 cases].
AB  - BACKGROUND: Selective serotonin reuptake inhibitors are widely used in the
      treatment of depressive and obsessive-compulsive disorders because of their low
      frequency adverse effects. We report two cases of cutaneous adverse effects
      during selective serotonin reuptake inhibitors therapy. CASE REPORTS: A man who
      complained of chronic anal idiopathic pruritus was treated with citalopram
      (Seropram(R)) 10 mg b.i.d. Six days after the beginning of the antidepressive
      treatment, he developed an extensive papular and purpuric erythema with
      keratinocytes necrosis and dermal leucocytoclastic vasculitis. Cutaneous lesions
      remained for several weeks, as the half-life of citalopram is very long (33 to 36
      hours) but did not relapse. A women developed painful papular and purpuric
      erythema mainly located in sun-exposed sites, during therapy with paroxetine
      (Deroxat(R)) 20 mg b.i.d., which had been introduced one month before to treat
      depression. Cutaneous lesions healed spontaneously in 2 weeks after the
      discontinuation of paroxetine and with sun avoidance and didn't relapse.
      DISCUSSION: Adverse cutaneous effects of selective serotonin reuptake inhibitors
      are rare but the knowledge of these reactions is important because toxic
      epidermal necrolysis and Stevens-Johnson syndrome had been reported during
      fluoxetine (Prozac(R)) and fluvoxamine (Floxyfral(R)) treatment. Different
      serotonin uptake blockers could be involved in the same allergic reaction,
      suggesting cross reactivity, although these drugs have different chemistry
      structures. It is advisable to substitute after an adverse effect a medication
      from one of the other classes of antidepressants.

PMID- 11460043
TI  - [Macrocheilitis].

PMID- 11460044
TI  - [Squamous plaques of the scalp in newborns].

PMID- 11460045
TI  - [Kawasaki's disease].

PMID- 11460046
TI  - [Role of the dermatologist in the prevention of occupational skin disease].

PMID- 11460047
TI  - [Side effects of intravenous immunoglobulin therapy].

PMID- 11460048
TI  - [Exploration of patients with suspected allergy to a local anesthetic].

PMID- 11460049
TI  - [Pseudoxanthoma elasticuna].

PMID- 11460050
TI  - [Acute lindane intoxication in three children].

PMID- 11460051
TI  - [Are new treatments always effective ?].

PMID- 11460052
TI  - [Non-healing leg ulcers].

PMID- 11460053
TI  - [Conjunctival provocation test with Dermatophagoides pteronyssinus in the
      diagnosis of allergic conjunctivitis from house mites].
AB  - INTRODUCTION: Perennial conjunctivitis due to house dust mites is the most
      frequent form of allergic conjunctivitis in urban environments. However, its
      diagnosis remains difficult for ophthalmologists. In this study, we evaluated a
      conjunctival provocation test (CPT) using standardized extracts of
      Dermatophagoides pteronyssinus (Dpt) and compared it to the diagnostic methods
      commonly performed in allergology: prick tests with dust and house dust mites and
      specific and IgE assay. MATERIALS AND METHODS: We performed a CPT on 60 volunteer
      patients, between the ages of 8 and 64 years, corresponding to 30 patients
      sensitized to house dust mites with the presence of specific IgE and chronic
      conjunctivitis, 21 patients not sensitized to house dust mites but presenting
      features of chronic conjunctivitis, and 9 asymptomatic patients. A house dust
      mite desensitizing treatment was not an exclusion criterion for a number of
      allergic patients. CPTs were prepared from Dpt allergenic extracts (Laboratoires
      Stallergenes, Antony, France) with 5 progressive concentrations by dilution in a
      nonphenolic physiological solution: 1.2 RI, 3.7 RI, 11 RI, 33 RI, and 100 RI.
      CPTs were performed in only one eye and asymmetry of the ocular response was
      evaluated by the cumulative clinical score of Abelson Chambers and Smith. The
      correlation between the 2 diagnostic tests was established by calculating the
      Cohen correlation coefficient or kappa. We also evaluated the sensitivity and
      diagnostic specificity for each test. RESULTS: The statistical correlation
      between specific IgE and the other allergological tests in for allergic
      conjunctivitis to house dust mites was 0.93 for the CPT, 0.46 for the prick test
      to Dpt, and 0.33 for the prick test to dust. The diagnostic sensitivities and
      specificities for each test were 90% and 100% for the CPT, 60% and 70% for the
      prick test to dust, 70% and 76% for prick test to Dpt, respectively. Beyond an
      antigenic cut-off value of 11 RI, we also observed greater hypersensitivity
      reactions for patients with lacrimal IgE or elevated specific IgE levels.
      CONCLUSION: The results obtained with the CPT confirm its high antigenic quality.
      It is a particularly useful, rapid, and perfectly safe clinical test. It is the
      only test able to establish a relationship between ocular manifestations and
      specific I(8)E.

PMID- 11460054
TI  - [Cataract surgery with posterior chamber lens implantation in Senegalese children
      less than 15 year-old].
AB  - PURPOSE: To assess short and medium term outcomes of cataract surgery with
      intraocular lens implantation in Senegalese children less than fifteen years.
      METHODS: From 1992 to 1997, 50 eyes of 40 children between the age of 5 months
      and 14 years, suffering from cataract were operated. Some of them were seen
      untill 2000. Twenty-seven cataracts were congenital, 19 were traumatic, 2 were
      from corticosteroid side effects, 1 after uveitis, and 1 had no determined cause.
      Thirty-one had manual extracapsular surgery and 19 ultrasound cataract surgery.
      They all have a standard single-piece PMMA intraocular lens of 21 to 22 diopters,
      12.0-12.5mm long, under the ciliaris silcus (34 cases) or in the capsular bag
      (16). The results were noted in the first week, at one month, at 3 months, and
      after. RESULTS: Exudative reactions were frequent in the anterior chamber: 20% of
      the eyes had such reactions during the operation, especially when a manual
      extracapsular extraction was performed, and 34% soon after operation. The
      reactions were generally revealed with one month of survey. Corticosteroids used
      before and after surgery reduced inflammation disorders but seemed to speed up
      the onset of secondary cataract. Posterior capsule opacification was observed in
      the first week after surgery. It increased from 45% at 3 months to 74% at 1 year
      and 100% after 3 years. Intraocular cristal lens implants are well tolerated with
      limited complications. Fifty-seven percent of the operated eyes we observed after
      3 years had 30/60 or better visual acuity. CONCLUSION: Despite fairly frequent
      inflammation and secondary cataract, posterior chamber lens implantation in
      children is well tolerated. This suggest that, as in adults, intraocular lens
      implant would be the best treatment for aphakia.

PMID- 11460055
TI  - [Infectious keratitis after penetrating keratoplasty].
AB  - PURPOSE: To investigate the prevalence of microbial keratitis, predisposing risk
      factors, the spectrum of pathogens and the prognosis for graft survival and
      visual outcome in patients who developed microbial keratitis following
      penetrating keratoplasty (PK). MATERIAL: and methods: We reviewed 16 cases (15
      patients) of microbial keratitis after PK. In all cases, corneal scrapings were
      obtained and microbiologically analyzed. Efficacy of treatment was evaluated by
      anatomical (clarity of graft) and visual recovery. RESULTS: Principal indications
      for PK were pseudophakic bullous keratopathy (50%) and microbial keratitis in the
      previous graft (25%). Sixty-three per cent of infections occurred within 1 year
      of PK. Principal predisposing risk factors were suture-related problems (44%) and
      microbial keratitis in the previous graft (25%). All of the scrapings were
      positive according to the microbiological evaluation with gram-positive cocci
      (64%), gram-positive rods (12%), fungi (18%), and Acanthamoeba (6%). We found 1
      case of polymicrobial infection. Best visual and anatomical results were observed
      in nonadvanced cases and/or these treated early. After medical and surgical
      treatments, 8 patients (50%) had a clear graft and 10 patients (63%) had visual
      acuity less than 20/200. CONCLUSION: Postoperative control of risk factors and
      early recognition of infectious complications may decrease the incidence of
      severe microbial keratitis after PK.

PMID- 11460056
TI  - [Diabetic retinopathy in Martinique: results of a cross-sectional survey based on
      771 patients].
AB  - INTRODUCTION: Because of the gravity of diabetic retinopathy in Martinique, a
      cross-sectional survey was conducted between March and September 1996 to estimate
      the prevalence of this complication on this island. PATIENTS AND METHODS:
      Clinical data, obtained by examining and questioning 771 diabetic patients
      (recruited among the usual practice of the ophthalmologists), were analyzed using
      Epi-Info. RESULTS: Some form of diabetic retinopathy was present in 42%. of the
      patients and 8.3% presented proliferative retinopathy. A total of 78% of the
      patients presented a non-insulin-dependent diabetes mellitus, essentially women.
      Medical supervision of the diabetes and its ophthalmologic complications proved
      to be insufficient. Principal risk factors found for the prevalence and severity
      of diabetic retinopathy were a long duration of diabetes, insulin-dependent type
      diabetes among women and the whole population, age among men, mode of treatment
      (insulin), and hypertension. DISCUSSION: These results are higher than those
      usually reported in France. This can be explained by diet and racial factors: the
      population is mainly of African and Indian descent. Risk factors are the same as
      those already described in earlier studies. To improve these prevalences,
      strategies should include classic methods risk factors correction, patients
      education, increasing coordination between the different medical specialists),
      but should also take into account the particularities of this Caribbean
      population such as racial, economic, historical, and sociocultural factors.

PMID- 11460057
TI  - [Risk factors for the degeneration of the choroid naevi: a retrospective study of
      135 cases].
AB  - INTRODUCTION: We have carried out a retrospective study of 135 patients followed
      at Curie Institute for choroidal naevus between March 1983 and June 1997.
      PATIENTS AND METHODS: 54 patients presented naevi considered as benign and 81
      patients presented suspicious choroidal naevi (with at least one of the following
      findings: visual symptoms; serious detachment of the retina; orange pigment;
      thickness greater than 2mm or a diameter greater than 7mm). These suspicious
      naevi were followed more carefully. The median follow-up was 49 months. The
      median diameter of the lesions was 6mm and the median thickness was 1.5mm. We
      studied the age of the patients, clinical symptoms, the presence or absence of
      orange pigment, drusen and serious detachment, and the angiographic and
      echographic findings. RESULTS: 3 patients died of unrelated cause; 7 patients
      were lost to follow-up; 30 patients presented documented growth; 4 of them
      belonged to the group considered as benign and 26 to the group considered as
      suspicious, with a significant difference between the groups. The lesions that
      grew were treated by proton beam or I125 patches. The risk factors for growth
      that were statistically significant were the presence of visual symptoms, pin
      points, orange pigment, serous detachment and thickness greater than 2mm. With
      drusen, the risk for growth was significantly less. DISCUSSION: These results are
      very similar to those published in the literature concerning risk factors for
      growth of choroidal nevi. The absence of metastatic spread in patients whose nevi
      have grown show that it is possible to monitor choroidal naevi if there is a
      doubt as to the malignant or benign nature of the lesion. CONCLUSION: It is
      important to determine if a choroidal naevus is suspicious or benign and to
      propose closer follow-up for suspicious lesions.

PMID- 11460058
TI  - [Dermis fat graft. Use of surgical reconstruction of the cavities].
AB  - Dermis fat graft is a surgical technique that is nowadays well accepted for the
      reconstruction of the orbital cavities. The authors report the results and the
      follow-up of 17 dermis fat grafts carried out at the Reims Hospital between March
      1(st), 1987 and December 31(st)1999. They explain the modalities of the
      technique, its major indications and the possible complications. At Reims, the
      dermis fat graft is mainly done to resolve intraorbital implant extrusions.

PMID- 11460059
TI  - [Clinical course of ocular sarcoidosis in patients with histologically proven
      systemic sarcoidosis].
AB  - PURPOSE: We reviewed the clinical features, natural history and visual prognosis
      of 9 patients with histologically confirmed ocular and systemic sarcoidosis.
      PATIENTS: Nine patients underwent a follow-up study between 1993 and 1998. The
      diagnosis of sarcoidosis was supported by histological evidence of non caseating
      epithelioid-cell granuloma in tissue biopsy. RESULTS: The mean age was 40.912
      years. The mean follow-up was 22.7 months (range 6 - 54 months). The ophthalmic
      involvement was bilateral in 8 patients. Before treatment, 3 eyes (17.6%) had a
      visual acuity less than 1/10. Two eyes (11.7%) had a visual acuity less than 3/10
      and 10 eyes (58.8%) more than 6/10. The anterior uveitis was granulomatous in 2
      eyes (11.7%) and non granulomatous in 8 eyes (47%). Five eyes (29.4%) had a pars
      planitis. The posterior segment manifestations of sarcoidosis were retinal
      vasculitis in 7 eyes (41.1%), papillitis in 10 eyes (58.8%) and choroidal
      granulomas in 2 eyes (11.7%). Seven patients were treated with systemic
      corticosteroids. One patient was treated with steroid eye-drops. After treatment,
      one eye (5.8%) had a visual acuity less than 1/10 and 13 eyes more than 6/10.
      After treatment, the choroidal granulomas disappeared and the intra-ocular
      inflammation was controlled in all cases. CONCLUSION: Although the number of
      patients in our series is small, the prognosis for ocular sarcoidosis appears to
      be good.

PMID- 11460060
TI  - [Iridocorneal endothelial syndrome. Series of 7 cases].
AB  - The ICE syndrome includes 3 variants of the same disease, previously believed to
      be independent entities. All 3 share clinical and histopathological features such
      as endothelial abnormalities, iris damage, and progressive closure of the
      iridocorneal angle. Seven cases of ICE syndrome are reported, affecting 6 women
      and 1 man, with a mean age of 40 years. Corectopia was found in 5 eyes, a uveal
      ectropion in 2 cases, and other iris changes in 3 cases. The endothelial changes
      of the cornea were confirmed by a speculum microscopy in 5 cases. There were 5
      cases of Chandler syndrome, 1 of Cogan-Reese syndrome, and 1 case of iris
      essential atrophy in our series. Ocular hypertony was observed in 3 cases, 2 of
      which needed to be operated. In one patient, a corneal edema was observed.

PMID- 11460061
TI  - [Keratitis due to caterpillar of Pseudosphinx tetrio hairs].
AB  - A case of keratitis due to caterpillar hairs of the Pseudosphinx tetrio is
      reported. As he was clearing his garden without glasses or a protective headgear,
      the patient felt left ocular pain due to the projection of a caterpillar into the
      eye. On examination, there were numerous intrastromal caterpillar hairs involving
      the inferior temporal quadrant of the cornea. The small size of the hairs
      prevented removal with forceps. The patient was treated by extensive washing of
      the eyeball and topical application of anti-inflammatory drugs, cycloplegics and
      antibiotics. The caterpillar hairs gradually came off the cornea over a two-weeks
      period. The cornea remained free of any scar. Besides keratitis and
      conjunctivitis, caterpillar hairs are known to cause iris nodules, chronic
      uveitis, cataract, hyalitis, chorioretinitis, and orbital cellulitis.

PMID- 11460062
TI  - [Conjunctival epithelial carcinoma in a 9-year-old child with xeroderma
      pigmentosum. Case report].
AB  - We report the case of a conjunctival tumor in a 9-year-old patient, suffering
      from Xeroderma Pigmentosum. Our patient presented a raspberry-colored
      conjunctival tumor. The tumor was resecked without any additional treatment. The
      histological study revealed squamous cell carcinoma. A suspicion of relapse
      appeared two months later of the same location and a new resection was performed.
      The initial checkup of this tumor was negative. In this disease, ocular
      localizations are frequent. The conjunctiva, the cornea, the eyelids and, into a
      lesser extent, the orbit can be involved. Basal cell carcinoma and squamous cell
      carcinoma are the most frequent tumors observed in Xeroderma Pigmentosum. Their
      treatment is mainly surgical.

PMID- 11460063
TI  - [The lipid layer of the lacrimal tear film: physiology and pathology].
AB  - The preocular tear film (POTF) is composed of a deep aqueous-mucin phase that
      supports a thin superficial lipid phase. The tear lipid layer (TLL), although
      thin, stabilizes the POTF providing a 25% surface-tension decrease and a 90-95%
      aqueous evaporation reduction. TLL is formed from lipids secreted by tarsal
      meibomian glands and spread onto the ocular surface by blinking. The TLL itself
      is composed of two phases. A thin and deep polar phase, adjacent to the aqueous
      mucin layer, has a surfactant role. A thicker and superficial nonpolar phase has
      antievaporative properties. At the same time, tear lipocalins help the TLL spread
      and stabilize the lipid-aqueous interface. For clinical examination, TLL is
      directly observed with the Tearscope. POTF stability and the evaporation rate
      depend on the lipid layer pattern. When chronic, POTF qualitative trouble
      (evaporative syndrome) due to a TLL anomaly, leads to secondary ocular surface
      impairment with increased tear instability and self-propagation of ocular
      dryness. Meibomian gland dysfunction (MGD) results from local pathology,
      dermatologic disease (ocular rosacea) or iatrogenic etiology. Cosmetic use is the
      other principal cause of TLL destabilization. Lid hygiene is the mainstay of MGD
      treatment. Systemic antibiotics (cyclins) can be associated in cases of severe
      symptoms. Topical treatment is useful if there is marginal lid inflammation or
      infection.

PMID- 11460064
TI  - [The eye and circadian rhythms].

PMID- 11460065
TI  - [Sympathetic ophthalmia complicated by subretinal neovascularization].

PMID- 11460066
TI  - [Epithelial cyst in the superior internal angle: a case report].
AB  - Most orbital cysts in childhood are epidermoids or dermoids. We report one
      uncommon case of an 8-years old girl with a lacrimal orbital cyst revealed by
      discrete proptosis and pseudo-ptosis in which the cystic histopathological study
      revealed a lacrimal structure.

PMID- 11460067
TI  - [Ophthalmological treatment of facial paralysis].

PMID- 11460068
TI  - [Clinical relevance of unusual metastases from colorectal neoplasms].
AB  - BACKGROUND: The aim of the study was to evaluate the clinical relevance of
      isolated metastases (MII) in unusual sites (different from liver and lung),
      synchronous and metachronous, in patients operated on for colorectal carcinoma
      (CCR). METHODS: The study was performed on 655 patients who underwent surgery for
      CCR during the period 1985-2000. Work out for distance metastases was performed
      (both during preoperative evaluation and follow-up) with physical examination and
      other few exams (CEA, chest X-ray, abdominal US scan). Other investigations were
      carried out if requested by clinical features. Metastases localized in sites
      different from liver and lungs were considered unusual. RESULTS: Metastases in
      unusual sites usually are observed in patients with terminal neoplastic disease.
      MII was found in only 7 (1.07%) patients, all submitted to resection of the
      primary tumor. Sites of unusual metastases were bones (3), CNS (2), adrenal gland
      and anus; such lesions were easily diagnosed by clinical features or by few
      examinations. Curative treatment was feasible in only three patients, and
      actually it did improve neither survival, nor quality of life. CONCLUSIONS: Extra
      abdominal MII are rare, generally they cannot be treated; therefore particular
      tests for early diagnosis of such lesions appear useless. Potentially curative
      surgery for splenic and adrenal metastases is described in the literature; anyhow
      these lesions are usually shown by routine investigations.

PMID- 11460069
TI  - [Stomach lymphoma].
AB  - BACKGROUND: Primitive gastric lymphoma (PGL) is a rare tumour, and although its
      incidence is rising it is difficult to state the role of the various therapeutic
      methods in treating this disease. Aim of this study is to point out what sequence
      of treatment is more effective trying to find out some guidelines which can be
      useful in clinical practice. METHODS: Retrospective analysis of clinical data of
      54 patients with PGL admitted at a University surgical department during 10
      years. All the patients underwent neoadjuvant or adjuvant chemotherapy and D2
      gastrectomy. Follow-up ranged from 6 to 120 months. Survival was related to:
      Mushoff's stage of disease, the grade according to the Working Formulation and
      the sequence of treatment. Statistical analysis was performed by Kaplan-Maier
      method and the difference between survival curves was compared by log-rank test.
      RESULTS: Mean postoperative hospital stay was 12 days and morbidity was 18%. Five
      and 10 years overall survival rates were 70 and 85%. There was a significant
      difference in survival between patients with high grade PGL and those with
      intermediate grade (p=0.0188) as well as in those with low grade (p=0.0435).
      Patients in stages IE-II1E had a significantly longer survival than those in
      stages IIIE-IVE (p=0.0123). Patients in stages IE-II1E underwent neadjuvant
      chemotherapy and surgery and survived longer than those in whom surgery preceded
      chemotherapy (p=0.0293) instead for patients in stages IIIE-IVE neoadjuvant
      chemotherapy shortened survival (p=0.0403). CONCLUSIONS: In personal opinion, in
      patients in stages IE-II1E chemotherapy should be carried out before surgery,
      while in those in stages IIIE-IVE the reverse scheme is more effective in
      achieving longer survival rates.

PMID- 11460070
TI  - [Biliary-intestinal bypass in the treatment of severe obesity: personal
      experience with 23 patients].
AB  - BACKGROUND: The aim of this study was to determine the efficacy and safety of
      biliary-intestinal bypass in severely obese subjects (Body Mass Index > 35).
      METHODS: From January to December 1999, 23 patients (8 men and 15 women, mean age
      36.6 years: range 20-51) affected with primary morbid obesity (BMI >40: range
      40.1-64.7), in whom different attempt using conservative medicine have proved non
      resolutive, underwent biliary-intestinal bypass. After the operation all the
      patients have been followed- up for 12 months. RESULTS: The mean Body Mass Index
      was reduced to 36.9 (range 27.7-44.1) after 6 months and to 33 (range 24.9-40.1)
      after 12 months. Peri and postoperative mortality was zero. Excessive
      malabsorption was efficaciously controlled by adequate replacement therapy.
      Diarrhoea, common compliance of every operation inducin malabsorbition, was
      reduced to 2-3 evacuation a day after 2-3 months. CONCLUSIONS: On the basis of
      personal experience it is underlined that biliary-intestinal bypass, as surgical
      treatment of morbid obesity refractory to medical therapy, is today a safe and
      effective operation (up to 80% of excess body weight lose); the presence of
      biliary-intestinal anastomosis reduces the post-operative loss of bile acids,
      choleretic diarrhoea and electrolytic disorders.

PMID- 11460071
TI  - The surgical treatment of pancreatic pseudocysts. Personal experience.
AB  - BACKGROUND: This study is aimed at contributing to defining a correct therapeutic
      management of pancreatic pseudocysts (PPCs): indications for treatment, operative
      timing and technical approach. METHODS: A retrospective analysis of 28 patients
      affected by PPC, 22 males (78.5%) and 6 females (21.5%), with a mean age of 52
      years (range 17-76) has been performed. The diagnosis was realised by clinical
      assessment and US (ultrasonography) or CT (computerized tomography) scanning. The
      treatment consisted in surgical drainage (internal or external) or percutaneous
      drainage with US guidance: the cystojejunostomy with a Roux-en-Y loop was the
      first choice technique. RESULTS: Twenty-two patients (78.5%) under-went a
      surgical procedure: 19 cystojejunostomies with a Roux-en-Y loop and 3 external
      drainages. The mean interval between acute pancreatic event and elective surgery
      was 9 weeks (range 5-21). Perioperative morbidity and mortality was respectively
      22.7% (5/22) and 13.6% (3/22). In 4 cases a percutaneous drainage with US
      guidance, without morbidity and mortality was performed, but 2 patients required
      a successive surgical operation for lack of resolution of the PPC. The last 2
      patients of this series recovered spontaneously. CONCLUSIONS: Currently the
      cystojejunostomy with a Roux-en-Y loop remains the first choice technique for an
      elective and definitive treatment of PPCs: other techniques (endoscopic internal
      drainage, surgical or percutaneous external drainage) should be limited to
      complicated PPCs or to high surgical risk patients. A waiting period of 4-6 weeks
      following the acute pancreatic event is considered the minimal time necessary
      before the elective treatment.

PMID- 11460072
TI  - [Fecal incontinence. Personal experience in direct sphincteric repair].
AB  - BACKGROUND: Fecal incontinence is a disabling condition causing social isolation,
      whose real incidence is difficult to be exactly valued because patients are often
      reluctant to speak about it, even with their physician, or because they don't
      trust on surgical procedure. Aim of this study is report our experience in
      sphincteric reconstruction by direct sphincteric repair in patients suffering
      from post-traumatic fecal incontinence. METHODS: Seven patients suffering from
      fecal incontinence due to traumatic lesions of anal sphincterial apparatus were
      surgically treated between 1981-2000; in the first patient cause was an injury
      due to impaling, in the second a previous obstetrical lesion and in the last five
      a previous fistulectomy. Direct sphincteric reconstruction after finding and
      isolation of two retracted terminals of sectioned sphincter was performed in all
      the patients. Sphincteric reconstruction has been always accompanied by total
      parenteral nutrition for about two weeks during the postoperative period. A
      protective colostomy was never performed. RESULTS: In five cases the results were
      excellent: patients had continence total recovery and postoperative manometry
      recorded basal and voluntary contraction pressures normalisation. In the two
      remaining cases there was only a modest improvement because of concomitant
      pudendal neuropathy. No operative wound infection was observed. CONCLUSIONS: We
      hope that more attention is paid to fecal incontinence either regarding
      instrumental semeiotics or medical or surgical therapy. In particular, direct
      sphincteroplasty can restore a satisfactory continence in a strong number of
      patients with anal sphincterial apparatus single traumatic lesions without
      pudendal neuropathy, relieving them from a heavily disabling condition.

PMID- 11460073
TI  - [Endoscopic perforating vein surgery. Review of the literature and personal
      experience].
AB  - The endoscopic treatment of perforating veins incompetence of the legs has been
      recently introduced as an effective surgical therapy in serious cases of chronic
      venous insufficiency. According to CEAP classification, the primary indication is
      set on the class 5 or 6 patients, affected by active ulcers or relapsing
      ulcerative lesions. During the last two years, 53 operations of SEPS have been
      performed at the Vascular Surgery Unit of G. Salvini Hospital in Garbagnate
      Milanese. Here we present A perspective study of 24 cases with a 6 to 18 months
      follow-up is presented. In 8 patients (33%) an active ulcer was present, while in
      16 cases history of relapsing ulcers was described. After the first month, all
      the lesions were healed and a subjective clinical improvement of the
      hypodermosclerosis was observed. At 12 months follow-up new ulcerations appeared
      only in four patients. On the basis the experiences of many authors and the
      results obtained in this study, following conclusions are made: the best results
      are achieved in case of sole perforating veins incompetence; the insufficiency of
      superficial venous circulation must be treated simultaneously or better
      previously, considering later the operation on the perforators veins; the
      sclerotherapy is introduced to cure the ectasic superficial veins in order to
      avoid a sponge effect with a precocious reappearance of the ulcers.

PMID- 11460074
TI  - [Role of the subfascial endoscopic perforating veins surgery in the treatment of
      venous ulceration: physiopathology and diagnosis].
AB  - Chronic venous insufficiency is a recurrent pathology, but affected patients
      often undergo clinical observation at a most severe and clearly symptomatic stage
      of the disease. In this late stage, therapy can only relieve symptoms of the
      disease which often lead to disability. In the clinical course of chronic venous
      insufficiency, phlebostatic ulceration constitutes a recurrent finding and it is
      responsible of compromising patients quality of life. The role of perforating
      veins, made refluxive by various pathogenic noxa, in the genesis of ulcerative
      lesions has been known since long time. For many years the interest in
      perforating veins surgery has been limited because of the several negative
      consequences of the operations. The possibility of modifying the hemodynamics of
      perforating veins compartment without causing post-operation complications by
      video-supported surgery, led to the debate on the role of these vessels in the
      chronic venous insufficiency. The phlebostasis non-invasive diagnosis uses
      imaging techniques consisting in tests which mostly are cheap, simple and easy to
      perform, thus representing the best early approach to the patient. It is widely
      thought that even though complex examinations are available, most precious
      information can be obtained by only two examinations: color-Doppler
      ultrasonography and, limitedly, plethysmography. By these diagnostic directions
      it is possible to better identify the site and the hemodynamic origin of the
      venous insufficiency.

PMID- 11460075
TI  - [Lung surgery in the elderly].
AB  - Lung surgery in the elderly, once considered a major risk, to be avoided if
      possible has become more popular in recent years as a result of many factors.
      First: lung cancer incidence has increased significantly in every age group but
      mostly in the elderly. Second: diagnosis at an early stage of the disease is
      higher in patients over 70 due to more frequent medical control in old subjects.
      Third: we now have more and more humans over 80 and a life expectancy increasing
      over the years. Fourth: preoperative, operative and postoperative medical
      supports are now safer and more reliable than previously. Operability criteria in
      the elderly are substantially the same as in younger group of patients for lung
      cancer. There are no reasons to refuse surgery in a subject over 80 because he is
      old. Lobectomy is the procedure of choice for lung cancer even in the elderly.
      Pneumonectomy must be avoided preferring a less radical procedure (wedge
      resection) so avoiding the risk of a postoperative respiratory failure that is
      often fatal for a patient with in border line functional respiratory tests, as
      often happens in the elderly. Thoracoscopic atypical resections must be
      considered in patients when a wedge resection is indicated preoperatively and
      almost always metastatic pulmonary lesion.

PMID- 11460076
TI  - [Small bowel diverticula in adults: clinical and therapeutic features. Report of
      2 cases and review of the literature].
AB  - The true diverticula of the small bowell are a very rare observation in clinical
      practice; they have a malformative origin and, occasionally, are acquired,
      contrary to what observed in the colon, where they are frequently an acquired
      pathology. They can involve the small bowel as a single lesion (Meckel's
      diverticulum), or as a segmentary disease (duodenal diverticula), or as a
      diffused diverticulosis. Generally they are asymptomatic and rarely they produce
      a true pathology. The symptomatic disease is primarily found in pediatric age and
      it requires a surgical procedure. This makes even more rare the diverticular
      pathology in the adult. The authors report 1 case of intestinal occlusion due to
      ileoileo-colic invagination arising from a Meckel's diverticulum and 1 case of
      intestinal occlusion in presence of a severe and acute diffuse diverticulosis of
      the small bowell, both in adult patients.

PMID- 11460077
TI  - [Subcutaneous emphysema. Complication associated with pneumoperitoneum during
      videolaparoscopic cholecystectomy].
AB  - Diagnostic and therapeutic laparoscopy is a safe procedure, which, however, is
      not without complications. The rare occurrence of subcutaneous emphysema, as a
      consequence of pneumoperitoneum, following laparoscopic cholecystectomy, is
      reported. The mechanism for the development of this complication and its
      management are discussed.

PMID- 11460078
TI  - [Serious complications of vertical banded gastroplasty. Case report].
AB  - Vertical banded gastroplasty, reported by Mason in 1982, is an effective method
      to control pathologic obesity (BMI>40 kg/m2). With the widespread of this
      procedure and the introduction of laparoscopic approach several complications are
      described in literature: gastroesophageal reflux, esophagitis, gastritis, gastric
      bleeding and perforations, prolonged vomit, dislocation of gastric ring,
      cholelithiasis, gastric fistulas, gastric stomal stenosis, dehiscence of vertical
      stomach staple line. From 2 to 10% of patients are reoperated because of
      inefficacy of treatment or short and long-term complications. Morbidity and
      mortality associated to reoperations are still high and it is difficult to
      identify criteria for an appropriate revision procedure. This can occur through
      endoscopy, laparotomy or laparoscopy, depending on clinical and radiologic
      feature. Dehiscence of vertical stomach staple line, observed in 10-20% of cases,
      even if asymptomatic, can lead to bad complications such as fistulas, peritonitis
      and sepsis. The case of a young woman, who underwent a vertical banded
      gastroplasty for pathologic obesity (117 kg, h 167 cm, BMI 42/m2) and subsequent
      laparotomies in the attempt to correct vertical staple line dehiscence, is
      reported. The patient came to our observation in a septic shock caused by
      peritonitis and ARDS and a total gastrectomy with Roux-en-Y esophago-jejunostomy
      was performed.

PMID- 11460079
TI  - [Frantz's solid cystic papillary pancreatic carcinoma].
AB  - The authors report their own case of a young woman recently operated for a rare
      form of pancreatic tumor of exocrine origin, so-called Frantz's solid-cystic
      papillary carcinoma, for which only a little more than 300 cases have been
      reported in the world literature. The authors discuss the pathogenesis (it is
      possible that Frantz's tumor is related to female sex hormones that may play a
      role in its growth but not in its genesis), clinical (the presentation is not
      specific and, despite the aid of modern diagnostic imaging, the preoperative
      diagnosis may be very difficult and this unusual tumor should be considered in
      the differential diagnosis of large abdominal masses, especially in young
      females), histological, radiological and surgical features of this tumor. The
      recommended treatment, given the low grade of malignancy of the tumor and the
      excellent overall prognosis, has to be as conservative as possible, with respect
      to the oncological radicality, but every attempt should be made for complete
      excision since surgical curability is high and radio-chemo-therapy is of no use
      for its treatment. Since regrowth of the tumor may occur, prolonged follow-up is
      mandatory.

PMID- 11460080
TI  - Laparoscopic Nissen fundoplication.
AB  - Open Nissen fundoplication has been established as an effective treatment in the
      management of gastroesophageal reflux disease (GORD). Progress in minimally
      invasive surgery has given the chance of performing laparoscopic Nissen
      fundoplication. The short-term results are encouraging and its outcome promising.
      The need for long-term medication ceases and it has already widely replaced the
      open procedure. Furthermore, the laparoscopic procedure can achieve the repair of
      any hiatal defect present. Thorough preoperative evaluation is imperative,
      because it determines the indication for surgery as well as the sort of
      operation. The laparoscopic procedure ensures a meticulous dissection and full
      mobilization of the lower oesophagus. These preconditions are of great importance
      in performing safely a floppy wrap. The method could be followed by complications
      or failure. Appropriately designed modern equipment is necessary. Thus, much
      experience and adequate training are required for the perfect application of
      laparoscopic Nissen fundoplication.

PMID- 11460081
TI  - Use of Indermil tissue adhesive for closure of superficial skin lacerations in
      children.
AB  - BACKGROUND: The aim of this study was to assess the use of tissue adhesive for
      paediatric wound closure in a minor injuries environment. METHODS: A n-butyl 2
      cyanoacrylate adhesive formulation was used for the closure of traumatic skin
      lacerations in 56 children. RESULTS: Tissue adhesive succeeded in approximating
      skin margins in all cases. No episodes of wound dehiscence were experienced.
      There were no incidences of wound infection. CONCLUSIONS: This study indicates
      that this form of tissue adhesive can safely and effectively be utilised for
      traumatic superficial skin closure in children.

PMID- 11460082
TI  - [Introduction to multimedia. Hypertext in surgical oncology distant learning:
      theoretical and methodological basis].

PMID- 11460083
TI  - [Diaphragmatic post-traumatic right laceration caused by costal fracture].

PMID- 11460084
TI  - Editorial.

PMID- 11460085
TI  - From the Art Director's Desk.

PMID- 11460086
TI  - The actions of melanin and melanocyte stimulating hormone (MSH).
AB  - The skin, the largest organ of the body, plays an important role in the total
      metabolism of several hormones. Melanin, the major product of the melanocyte, is
      largely responsible for the coloring of skin. Melanin is a complex of insoluble,
      polyquinone, brown or red pigment and protein, formed by the oxidation of
      tyrosine and 3,4-dihydroxyphenylalanine in the presence of tyrosinase. There
      exists two main groups of melanin: the black to dark-brown insoluble eumelanins
      and the yellow to reddish brown, alkali-soluble pheomelanins. MSH, ACTH and beta
      lipoprotein are able to influence skin pigmentation. The functions attributed to
      melanins are acting as a barrier against ionizing radiation; participating in
      developmental processes, serving as a cosmetic entity, and scavenging cytotoxic
      radicals and intermediates. Melanocytes express numerous receptors that allow
      interaction with other cells in their microenvironment, including keratinocytes
      and the immune component of the skin Langerhans cells. Albinism represents a
      group of inherited abnormalities that present with congenital hypopigmentation
      that can involve the skin, hair, and eyes (oculocutaneous albinism) or be limited
      primarily to the eyes (ocular albinism). The inherited disorders of keratin
      include epidermolysis bullosu simplex causing cell degeneration within the basal
      layer. Sunlight and ultraviolet radiation from artificial light sources could be
      tonic or toxic to human skin. The harmful effects of solar radiation are skin
      cancer, photosensitivity diseases, sunburn, photoallergy, photoimmunologic
      alterations, cataracts, mutations, skin aging and phototoxicity. Sunscreen
      chemicals protect the skin against ultraviolet radiation.

PMID- 11460087
TI  - Metal-specific lymphocytes: biomarkers of sensitivity in man.
AB  - Many patients attribute their health problems to amalgam and other dental metals.
      In genetically susceptible indviduals, mercury and gold may function as haptens
      and elicit allergic and autoimmune reactions. The frequency of metal-induced
      lymphocyte responses was examined in 3,162 patients in three European
      laboratories using MELISA(R), an optimized lymphocyte proliferation test. The
      patients suffered from local and systemic symptoms attributed to dental
      restorations. The effect of dental metal removal was studied in 111 patients with
      metal hypersensitivity and symptoms resembling Chronic Fatigue Syndrome (CFS).
      After consultation with a dentist the patients decided to replace their metal
      restorations with non-metallic materials. The changes in health and in vitro
      lymphocyte reactivity were studied by inquiries and follow-up MELISA(R).
      Lymphocyte reactivity was also analyzed in 116 healthy subjects with no
      complaints of metal allergy. A significant number of patients had metal-specific
      lymphocytes in the blood. Nickel was the most common sensitizer, followed by
      inorganic mercury, gold, phenylmercury, cadmium and palladium. As compared to
      lymphocyte responses in healthy subjects, the CFS group had significantly
      increased responses to several metals, especially to inorganic mercury,
      phenylmercury and gold. Following dental metal removal, 83 patients (76%)
      reported long-term health improvement. Twenty-four patients (22%) reported
      unchanged health and two (2%) reported worsening of symptoms. Following dental
      metal replacement, the lymphocyte reactivity to metals decreased as well. We
      propose that an inflammatory process induced by metals may modulate the
      hypothalamic-pituitary-adrenal axis (HPA axis) and trigger multiple non-specific
      symptoms characterizing CFS and other chronic conditions like myalgic
      encephalitis (ME) and multiple chemical sensitivity (MCS).

PMID- 11460088
TI  - Wavelength dependency of light-induced changes in rhythmic melatonin secretion
      from chicken pineal gland in vitro.
AB  - Avian pineals show rhythmic, circadian melatonin secretion pattern also in vitro.
      The phase of this rhythm can be modified by changing the illumination. Reversed
      in vitro illumination reverses the phase of the circadian melatonin rhythm in two
      days. In the present study the effect of the wavelength on the speed of the phase
      shift of the melatonin rhythm of the explanted chicken pineals was investigated
      in a dynamic in vitro bioassay. Chicken pineals were placed into perifusion
      columns and the tissue was exposed to reversed illumination through various light
      filters. Changes in the melatonin release during 4 day long experiments were
      studied. Clear differences in the speed of the reversal of the melatonin rhythm
      were observed as a function of the transmission spectrum of the light filters.
      The shorter the transmitted wavelength, the more rapid the phase shift was found.
      These data are in good agreement with earlier studies showing that the chicken
      pineal photo-pigment, pinopsin, is a blue light sensitive molecule. Our
      observation reveals that the blue light sensitive pigment is not only present but
      also fully functional in controlling the circadian biological clock in the
      chicken pineal gland.

PMID- 11460089
TI  - Effect of isologous pineal transplants on tumorigenesis of autologous
      intrasplenic ovarian transplants in Swiss mice.
AB  - Intrasplenic ovarian tumorigenesis is the most suitable experimental model to
      study the role of hormones in carcinogenesis. If increased secretion of
      gonadotrophins causes ovarian tumorigenesis in the spleen, one can find ways to
      control the secretion of gonadotrophins so as to prevent the tumor formation.
      Pineal is the one gland which is known to regulate gonadotrophin secretion. In
      the present studies, isologous pineals were transplanted into the anterior eye
      chamber of Swiss females bearing autologous ovaries in the spleen, with
      appropriate controls. The results showed that two pineals maintained in the
      ocular chamber for four months could prevent tumor formation of the ovarian
      transplants in the spleen. Control animals maintained for the same period of time
      as experimental animals had ovarian transplants turn into a tumor. These
      experiments clearly demonstrated that the pineal had an inhibitory effect on
      intrasplenic ovarian tumorigenesis. Since two pineals were required to bring
      about the effect, it implies that the amount of the factor present in the
      endogenous gland is not enough to prevent the tumorigenesis. The inhibitory
      action in these experiments must be via the pituitary, since it is not inhibition
      of tumor growth but it is prevention of transformation of the normal ovary into a
      tumor. This prevention is possible only if hormone stress is withdrawn from the
      system. These results suggest the prospects of prevention of cancer by some
      factor present in the pineal.

PMID- 11460090
TI  - Peer review and editorial decision-making.

PMID- 11460091
TI  - Editor creates journal.

PMID- 11460092
TI  - Quantifying quality.

PMID- 11460093
TI  - Influence of hypovolemic and hypertonic treatments on plasma vasopressin levels
      and fluid balance in the propylthiouracil-induced hypothyroid rat.
AB  - This study was undertaken to investigate the effects of hypovolemic and
      hypertonic treatments on plasma vasopressin (AVP) levels and fluid balance in
      propylthiouracil (PTU)-induced hypothyroidism in the rat. The influence of
      hypothyroidism on AVP responsiveness to hypertonic and hypovolemic stimuli were
      compared. Adult male rats were divided into two groups. Groups I and II were
      intraperitoneally (i.p.) injected with saline (1ml/250g) and PTU (10mg/kg/day),
      respectively, for a period of two weeks. These groups were further divided in
      three subgroups each containing six rats. The first subgroup consisted of
      unchallenged rats. I.P. 700 mg polyethylene glycol was used for hypovolemic
      treatment. The third subgroup consisted of hypertonic (1.5 M NaCl; 1ml/100 g)
      stimulated animals. All rats were decapitated and trunk blood collected in hep
      arinized tubes. Plasma samples were stored at -20 degrees C until assayed. Plasma
      AVP, T3 and T4 levels were measured by radioimmunassay. Hematocrit values and
      plasma Na concentrations were also determined. In the PTU-induced hypothyroid
      rats, hypertonic treatment caused lower increase in plasma AVP levels (p<0.05)
      compared to the respective control animals. In the hypovolemic group, decreases
      in AVP responses were not found to be statistically significant. In conclusion,
      although hypothyroidism does not statistically change basal AVP levels, it may
      affect AVP response to hypertonic stimulus. It is not clear whether changes in
      fluid-electrolyte balance cause disturbance in AVP release in hypothyroidism or
      vice versa. Therefore, these preliminary findings need to be confirmed by further
      investigations.

PMID- 11460094
TI  - Distribution of serotonin and its effect on insulin and glucagon secretion in
      normal and diabetic pancreatic tissues in rat.
AB  - OBJECTIVES: The distribution of serotonin (5-HT) and its effect on insulin and
      glucagon secretion were investigated to examine whether there are changes in the
      pattern of distribution and effect of 5-HT after the onset of experimental
      diabetes. METHODS: The pattern of 5-HT and its effect of insulin and glucagon
      secretion was examined using immunohistochemical and radioimmunoassay techniques,
      respectively. RESULTS: 5-HT was demonstrated mainly in the neural elements of the
      pancreas. 5-HT-containing fine varicose nerve fibers were discerned in the wall
      of blood vessels and pancreatic ducts. 5-HT-containing nerves were also observed
      in the periacinar and periinsular regions of normal pancreas. The pattern or
      intensity of the distribution of serotonergic nerves did not change after the
      onset of diabetes. The perivascular, periductal, periacinar and periinsular
      regions of diabetic pancreas all contained 5-HT positive nerves. 5-HT elicited
      marked increases in insulin secretion from normal pancreas but had an inhibitory
      effect on insulin secretion from diabetic pancreatic tissues. In contrast, 5HT
      inhibited glucagon secretion from normal pancreatic tissue fragments but
      stimulated glucagon release from diabetic pancreatic tissue fragments.
      conclusion: 5-HT is well distributed in normal and diabetic pancreatic tissues
      and has stimulatory effects on insulin secretion from normal pancreas and
      glucagon secretion from diabetic pancreas. This result indicates that although 5
      HT may help in the maintenance of the blood sugar level in normal pancreas by
      increasing insulin secretion and decreasing glucagon secretion, it may also
      aggravate the hyperglycemia observed in diabetes mellitus and hence exacerbate
      the symptoms of hyperglycemia in poorly controlled diabetes mellitus.

PMID- 11460095
TI  - Endocrinological and genetic studies in patients with Polycystic Ovary Syndrome
      (PCOS).
AB  - Our studies involved 21 women of Caucasian descent with PCOS, as diagnosed by
      ultrasound, clinical and hormonal findings. We determined 17alpha-OHP, 21-DOF and
      cortisol levels both just before and one hour after intravenous ACTH
      administration (0.25 mg Synacthen) in addition to the basal plasma levels of DHEA
      S and free testosterone. We screened the CYP21 gene for 12 common-point
      mutations, finding five heterozygous mutations in 4 out of 21 cases (19%): a
      splice-site mutation in intron 2 in three cases, and a I172N mutation in exon 4
      in two cases. These patients also displayed significantly higher 21-DOF or
      17alpha-OHP plasma levels after ACTH administration, suggesting a partial 21
      hydroxylase deficiency. Furthermore, we found the basal plasma DHEA-S levels or
      DHEA-S/F ratios in 11 of 21 patients (52%) to be higher than the means + 2SD of
      control females, indicating partial 3beta-HSD deficiency or 17,20-LHA. According
      to the literature, mutations could not be found in the genes of PCO cases with
      hormonal activity changes in the last two enzymes. The DDT metabolite o,p'-DDD is
      a strong inhibitor of 3beta-HSD, and DDT can induce 17,20-LHA, implying a
      possible connection between cases of PCOS women born in East Germany after 1955
      and their prenatal DDT uptake. The approximately fourfold higher prevalence of
      PCO and significantly increased frequency of 3beta-HSD-deficiency and 17,20-LHA
      found in women with PCOS born since 1955-the time of massive application of DDT
      give weight to the thesis that DDT, rather than genetic factors, has played a
      part in this upsurge.

PMID- 11460096
TI  - Meeting hints at thaw in relations between genome rivals.

PMID- 11460097
TI  - Max Planck Society admits to its predecessor's Nazi links.

PMID- 11460098
TI  - Pathogen threat spurs research initiatives.

PMID- 11460099
TI  - UK election sees revamp for farming and environment.

PMID- 11460100
TI  - Referendum stalls Japanese nuclear power strategy.

PMID- 11460103
TI  - The philosopher's child.

PMID- 11460101
TI  - Airborne telescope delayed as plane is made ready.

PMID- 11460104
TI  - Scanning the mental continuum.

PMID- 11460105
TI  - In search of perfection.

PMID- 11460107
TI  - 100 and 50 years ago.

PMID- 11460106
TI  - Science in culture.

PMID- 11460108
TI  - DaedalusThe tense road.

PMID- 11460109
TI  - reply: Neurobiologyp25 protein in neurodegeneration.
AB  - Yoo and Lubec show that the amount of p25 is decreased in the brains they studied
      from patients with Alzheimer's disease or Down's syndrome. Their results
      persuaded us to conduct a more extensive survey of the p25/p35 ratio in AD brains
      (to be published elsewhere), as the number of samples was small in both of our
      studies (eight AD brains in our original study and six in theirs). After
      analysing a further 25 AD brains and those from 25 age-matched controls, we found
      that p25 levels are consistently higher in AD brains and that the difference is
      statistically significant (Student's t-test). This is in agreement with our
      original observations, as well as being consistent with earlier reports of
      increased Cdk5 kinase activity in AD brain and of increased amounts of p25 in an
      animal model of neurodegeneration.

PMID- 11460111
TI  - correction: Enabling the chemistry of life.

PMID- 11460110
TI  - correction: Plant diversity enhances ecosystem responses to elevated CO2 and
      nitrogen deposition.

PMID- 11460113
TI  - Lab automation.

PMID- 11460112
TI  - Plant defence.

PMID- 11460114
TI  - The meaning of life.

PMID- 11460115
TI  - Can the leopard change its spots?

PMID- 11460116
TI  - Britain seeks transgenics deal to fend off transatlantic trade war.

PMID- 11460117
TI  - Smithsonian head ruffled by inquiry.

PMID- 11460119
TI  - Simple technology could reclaim America's lost votes.

PMID- 11460118
TI  - Millennium Dome sees signs of a Wellcome break.

PMID- 11460120
TI  - Congress touts budget boost for NASA and the NSF.

PMID- 11460121
TI  - Physical sciences lose ground as US shifts towards biology.

PMID- 11460122
TI  - Search for alien life reasserts its credibility.

PMID- 11460123
TI  - Action urged to combat killer algae.

PMID- 11460124
TI  - Outbreak of chicken flu rattles Hong Kong.

PMID- 11460125
TI  - Disgruntled homeopathists seek remedy in court.

PMID- 11460128
TI  - Forza scienza!

PMID- 11460129
TI  - Windows on the brain.

PMID- 11460130
TI  - Making sure that the world's palaeodata do not get buried.

PMID- 11460131
TI  - Who will organize sharing of biodiversity data?

PMID- 11460132
TI  - Mistaken identity in a watery arms race.

PMID- 11460133
TI  - Mission now possible for AIDS fund.

PMID- 11460135
TI  - Success hinges on support for treatment.

PMID- 11460140
TI  - Walking with producers.

PMID- 11460141
TI  - The fog that was not.

PMID- 11460142
TI  - New-age drug meets resistance.

PMID- 11460143
TI  - Astronomy. Dark arc casts a long shadow.

PMID- 11460144
TI  - Signal transduction. An alternative to destruction.

PMID- 11460146
TI  - Biogeochemistry. Space for hydrogen.

PMID- 11460147
TI  - Immunology. End game for B cells.

PMID- 11460148
TI  - Superconductivity. Iron cast in exotic role.

PMID- 11460149
TI  - Cell biology. Cytoskeleton in the cell cycle.

PMID- 11460151
TI  - Nile flooding sank two ancient cities.

PMID- 11460152
TI  - Animal behaviour. An unusual social display by gorillas.

PMID- 11460153
TI  - Dynamics of collapsing and exploding Bose-Einstein condensates.
AB  - When atoms in a gas are cooled to extremely low temperatures, they will-under the
      appropriate conditions-condense into a single quantum-mechanical state known as a
      Bose-Einstein condensate. In such systems, quantum-mechanical behaviour is
      evident on a macroscopic scale. Here we explore the dynamics of how a Bose
      Einstein condensate collapses and subsequently explodes when the balance of
      forces governing its size and shape is suddenly altered. A condensate's
      equilibrium size and shape is strongly affected by the interatomic interactions.
      Our ability to induce a collapse by switching the interactions from repulsive to
      attractive by tuning an externally applied magnetic field yields detailed
      information on the violent collapse process. We observe anisotropic atom bursts
      that explode from the condensate, atoms leaving the condensate in undetected
      forms, spikes appearing in the condensate wavefunction and oscillating remnant
      condensates that survive the collapse. All these processes have curious
      dependences on time, on the strength of the interaction and on the number of
      condensate atoms. Although the system would seem to be simple and well
      characterized, our measurements reveal many phenomena that challenge theoretical
      models.

PMID- 11460154
TI  - Plasma cell differentiation requires the transcription factor XBP-1.
AB  - Considerable progress has been made in identifying the transcription factors
      involved in the early specification of the B-lymphocyte lineage. However, little
      is known about factors that control the transition of mature activated B cells to
      antibody-secreting plasma cells. Here we report that the transcription factor XBP
      1 is required for the generation of plasma cells. XBP-1 transcripts were rapidly
      upregulated in vitro by stimuli that induce plasma-cell differentiation, and were
      found at high levels in plasma cells from rheumatoid synovium. When introduced
      into B-lineage cells, XBP-1 initiated plasma-cell differentiation. Mouse lymphoid
      chimaeras deficient in XBP-1 possessed normal numbers of activated B lymphocytes
      that proliferated, secreted cytokines and formed normal germinal centres.
      However, they secreted very little immunoglobulin of any isotype and failed to
      control infection with the B-cell-dependent polyoma virus, because plasma cells
      were markedly absent. XBP-1 is the only transcription factor known to be
      selectively and specifically required for the terminal differentiation of B
      lymphocytes to plasma cells.

PMID- 11460155
TI  - A massive cloud of cold atomic hydrogen in the outer Galaxy.
AB  - A large fraction of the mass of the interstellar medium in our Galaxy is in the
      form of warm (103-104 K) and cool (50-100 K) atomic hydrogen (H i) gas. Cold (10
      30 K) regions are thought to be dominated by dense clouds of molecular hydrogen.
      Cold H i is difficult to observe, and therefore our knowledge of its abundance
      and distribution in the interstellar medium is poor. The few known clouds of cold
      H i are much smaller in size and mass than typical molecular clouds. Here we
      report the discovery that the H i supershell GSH139-03-69 is very cold (10 K). It
      is about 2 kiloparsecs in size and as massive as the largest molecular complexes.
      The existence of such an immense structure composed of cold atomic hydrogen in
      the interstellar medium runs counter to the prevailing view that cold gas resides
      almost exclusively in clouds dominated by molecular hydrogen.

PMID- 11460156
TI  - Isotopic homogeneity of iron in the early solar nebula.
AB  - The chemical and isotopic homogeneity of the early solar nebula, and the
      processes producing fractionation during its evolution, are central issues of
      cosmochemistry. Studies of the relative abundance variations of three or more
      isotopes of an element can in principle determine if the initial reservoir of
      material was a homogeneous mixture or if it contained several distinct sources of
      precursor material. For example, widespread anomalies observed in the oxygen
      isotopes of meteorites have been interpreted as resulting from the mixing of a
      solid phase that was enriched in 16O with a gas phase in which 16O was depleted,
      or as an isotopic 'memory' of Galactic evolution. In either case, these anomalies
      are regarded as strong evidence that the early solar nebula was not initially
      homogeneous. Here we present measurements of the relative abundances of three
      iron isotopes in meteoritic and terrestrial samples. We show that significant
      variations of iron isotopes exist in both terrestrial and extraterrestrial
      materials. But when plotted in a three-isotope diagram, all of the data for these
      Solar System materials fall on a single mass-fractionation line, showing that
      homogenization of iron isotopes occurred in the solar nebula before both
      planetesimal accretion and chondrule formation.

PMID- 11460157
TI  - Entanglement of the orbital angular momentum states of photons.
AB  - Entangled quantum states are not separable, regardless of the spatial separation
      of their components. This is a manifestation of an aspect of quantum mechanics
      known as quantum non-locality. An important consequence of this is that the
      measurement of the state of one particle in a two-particle entangled state
      defines the state of the second particle instantaneously, whereas neither
      particle possesses its own well-defined state before the measurement.
      Experimental realizations of entanglement have hitherto been restricted to two
      state quantum systems, involving, for example, the two orthogonal polarization
      states of photons. Here we demonstrate entanglement involving the spatial modes
      of the electromagnetic field carrying orbital angular momentum. As these modes
      can be used to define an infinitely dimensional discrete Hilbert space, this
      approach provides a practical route to entanglement that involves many orthogonal
      quantum states, rather than just two Multi-dimensional entangled states could be
      of considerable importance in the field of quantum information, enabling, for
      example, more efficient use of communication channels in quantum cryptography.

PMID- 11460158
TI  - Superconductivity in the non-magnetic state of iron under pressure.
AB  - Ferromagnetism and superconductivity are thought to compete in conventional
      superconductors, although in principle it is possible for any metal to become a
      superconductor in its non-magnetic state at a sufficiently low temperature. At
      pressures above 10 GPa, iron is known to transform to a non-magnetic structure
      and the possibility of superconductivity in this state has been predicted. Here
      we report that iron does indeed become superconducting at temperatures below 2 K
      at pressures between 15 and 30 GPa. The transition to the superconducting state
      is confirmed by both a drop in resistivity and observation of the Meissner
      effect.

PMID- 11460159
TI  - Direct observation of hole transfer through DNA by hopping between adenine bases
      and by tunnelling.
AB  - The function of DNA during oxidative stress and its suitability as a potential
      building block for molecular devices depend on long-distance transfer of
      electrons and holes through the molecule, yet many conflicting measurements of
      the efficiency of this process have been reported. It is accepted that charges
      are transported over long distances through a multistep hopping reaction; this 'G
      hopping' involves positive charges moving between guanines (Gs), the DNA bases
      with the lowest ionization potential. But the mechanism fails to explain the
      persistence of efficient charge transfer when the guanine sites are distant,
      where transfer rates do not, as expected, decrease rapidly with transfer
      distance. Here we show experimentally that the rate of charge transfer between
      two guanine bases decreases with increasing separation only if the guanines are
      separated by no more than three base pairs; if more bridging base pairs are
      present, the transfer rates exhibit only a weak distance dependence. We attribute
      this distinct change in the distance dependence of the rate of charge transfer
      through DNA to a shift from coherent superexchange charge transfer (tunnelling)
      at short distances to a process mediated by thermally induced hopping of charges
      between adenine bases (A-hopping) at long distances. Our results confirm
      theoretical predictions of this behaviour, emphasizing that seemingly
      contradictory observations of a strong as well as a weak influence of distance on
      DNA charge transfer are readily explained by a change in the transfer mechanism.

PMID- 11460160
TI  - Thermolysis of fluoropolymers as a potential source of halogenated organic acids
      in the environment.
AB  - Following the introduction of hydrochlorofluorocarbon (HCFCs) and
      hydrofluorocarbon (HFCs) gases as replacements for the ozone-destroying
      chlorofluorocarbons (CFCs), it has been discovered that HCFCs/HFCs can degrade in
      the atmosphere to produce trifluoroacetic acid, a compound with no known loss
      mechanisms in the environment, and higher concentrations in natural waters have
      been shown to be mildly phytotoxic. Present environmental levels of
      trifluooracetic acid are not accounted by HCFC/HFC degradation alone. Here we
      report that thermolysis of fluorinated polymers, such as the commercial polymers
      Teflon and Kel-F, can also produce trifluoroacetate and the similar compound
      chlorodifluoroacetate. This can occur either directly, or indirectly via products
      that are known to degrade to these haloacetates in the atmosphere. The
      environmental significance of these findings is confirmed by modelling, which
      indicates that the thermolysis of fluoropolymers in industrial and consumer high
      temperature applications (ovens, non-stick cooking utensils and combustion
      engines) is likely to be a significant source of trifluoroacetate in urban rain
      water ( approximately 25 ng l-1, as estimated for Toronto). Thermolysis also
      leads to longer chain polyfluoro- and/or polychlorofluoro- (C3-C14) carboxylic
      acids which may be equally persistent. Some of these products have recently been
      linked with possible adverse health and environmental impacts and are being
      phased out of the US market. Furthermore, we detected CFCs and fluorocarbons
      groups that can destroy ozone and act as greenhouse gases, respectively-among the
      other thermal degradation products, suggesting that continued use of
      fluoropolymers may also exacerbate stratospheric ozone-depletion and global
      warming.

PMID- 11460161
TI  - The role of microbial mats in the production of reduced gases on the early Earth.
AB  - The advent of oxygenic photosynthesis on Earth may have increased global
      biological productivity by a factor of 100-1,000 (ref. 1), profoundly affecting
      both geochemical and biological evolution. Much of this new productivity probably
      occurred in microbial mats, which incorporate a range of photosynthetic and
      anaerobic microorganisms in extremely close physical proximity. The potential
      contribution of these systems to global biogeochemical change would have depended
      on the nature of the interactions among these mat microorganisms. Here we report
      that in modern, cyanobacteria-dominated mats from hypersaline environments in
      Guerrero Negro, Mexico, photosynthetic microorganisms generate H2 and CO-gases
      that provide a basis for direct chemical interactions with neighbouring
      chemotrophic and heterotrophic microbes. We also observe an unexpected flux of
      CH4, which is probably related to H2-based alteration of the redox potential
      within the mats. These fluxes would have been most important during the nearly 2
      billion-year period during which photosynthetic mats contributed substantially to
      biological productivity-and hence, to biogeochemistry-on Earth. In particular,
      the large fluxes of H2 that we observe could, with subsequent escape to space,
      represent a potentially important mechanism for oxidation of the primitive oceans
      and atmosphere.

PMID- 11460162
TI  - Reproductive pair correlations and the clustering of organisms.
AB  - Clustering of organisms can be a consequence of social behaviour, or of the
      response of individuals to chemical and physical cues. Environmental variability
      can also cause clustering: for example, marine turbulence transports plankton and
      produces chlorophyll concentration patterns in the upper ocean. Even in a
      homogeneous environment, nonlinear interactions between species can result in
      spontaneous pattern formation. Here we show that a population of independent,
      random-walking organisms ('brownian bugs'), reproducing by binary division and
      dying at constant rates, spontaneously aggregates. Using an individual-based
      model, we show that clusters form out of spatially homogeneous initial conditions
      without environmental variability, predator-prey interactions, kinesis or taxis.
      The clustering mechanism is reproductively driven-birth must always be adjacent
      to a living organism. This clustering can overwhelm diffusion and create non
      poissonian correlations between pairs (parent and offspring) or organisms,
      leading to the emergence of patterns.

PMID- 11460163
TI  - Evolution of digital organisms at high mutation rates leads to survival of the
      flattest.
AB  - Darwinian evolution favours genotypes with high replication rates, a process
      called 'survival of the fittest'. However, knowing the replication rate of each
      individual genotype may not suffice to predict the eventual survivor, even in an
      asexual population. According to quasi-species theory, selection favours the
      cloud of genotypes, interconnected by mutation, whose average replication rate is
      highest. Here we confirm this prediction using digital organisms that self
      replicate, mutate and evolve. Forty pairs of populations were derived from 40
      different ancestors in identical selective environments, except that one of each
      pair experienced a 4-fold higher mutation rate. In 12 cases, the dominant
      genotype that evolved at the lower mutation rate achieved a replication rate >1.5
      fold faster than its counterpart. We allowed each of these disparate pairs to
      compete across a range of mutation rates. In each case, as mutation rate was
      increased, the outcome of competition switched to favour the genotype with the
      lower replication rate. These genotypes, although they occupied lower fitness
      peaks, were located in flatter regions of the fitness surface and were therefore
      more robust with respect to mutations.

PMID- 11460164
TI  - Evolution and transmission of stable CTL escape mutations in HIV infection.
AB  - Increasing evidence indicates that potent anti-HIV-1 activity is mediated by
      cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on
      viral transmission and evolution have not been determined. Here we investigate
      mother-child transmission in the setting of human leukocyte antigen (HLA)-B27
      expression, selected for analysis because it is associated with prolonged immune
      containment in adult infection. In adults, mutations in a dominant and highly
      conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease
      progression. In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we
      document transmission of viruses encoding CTL escape variants in this dominant
      Gag epitope that no longer bind to B27. Their infected infants target an
      otherwise subdominant B27-restricted epitope and fail to contain HIV replication.
      These CTL escape variants remain stable without reversion in the absence of the
      evolutionary pressure that originally selected the mutation. These data suggest
      that CTL escape mutations in epitopes associated with suppression of viraemia
      will accumulate as the epidemic progresses, and therefore have important
      implications for vaccine design.

PMID- 11460165
TI  - An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming.
AB  - The priming step of synaptic vesicle exocytosis is thought to require the
      formation of the SNARE complex, which comprises the proteins synaptobrevin, SNAP
      25 and syntaxin. In solution syntaxin adopts a default, closed configuration that
      is incompatible with formation of the SNARE complex. Specifically, the amino
      terminus of syntaxin binds the SNARE motif and occludes interactions with the
      other SNARE proteins. The N terminus of syntaxin also binds the presynaptic
      protein UNC-13 (ref. 5). Studies in mouse, Drosophila and Caenorhabditis elegans
      suggest that UNC-13 functions at a post-docking step of exocytosis, most likely
      during synaptic vesicle priming. Therefore, UNC-13 binding to the N terminus of
      syntaxin may promote the open configuration of syntaxin. To test this model, we
      engineered mutations into C. elegans syntaxin that cause the protein to adopt the
      open configuration constitutively. Here we demonstrate that the open form of
      syntaxin can bypass the requirement for UNC-13 in synaptic vesicle priming. Thus,
      it is likely that UNC-13 primes synaptic vesicles for fusion by promoting the
      open configuration of syntaxin.

PMID- 11460166
TI  - Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas.
AB  - Genomic instability promotes tumorigenesis and can occur through various
      mechanisms, including defective segregation of chromosomes or inactivation of DNA
      mismatch repair. Although B-cell lymphomas are associated with chromosomal
      translocations that deregulate oncogene expression, a mechanism for genome-wide
      instability during lymphomagenesis has not been described. During B-cell
      development, the immunoglobulin variable (V) region genes are subject to somatic
      hypermutation in germinal-centre B cells. Here we report that an aberrant
      hypermutation activity targets multiple loci, including the proto-oncogenes PIM1,
      MYC, RhoH/TTF (ARHH) and PAX5, in more than 50% of diffuse large-cell lymphomas
      (DLCLs), which are tumours derived from germinal centres. Mutations are
      distributed in the 5' untranslated or coding sequences, are independent of
      chromosomal translocations, and share features typical of V-region-associated
      somatic hypermutation. In contrast to mutations in V regions, however, these
      mutations are not detectable in normal germinal-centre B cells or in other
      germinal-centre-derived lymphomas, suggesting a DLCL-associated malfunction of
      somatic hypermutation. Intriguingly, the four hypermutable genes are susceptible
      to chromosomal translocations in the same region, consistent with a role for
      hypermutation in generating translocations by DNA double-strand breaks. By
      mutating multiple genes, and possibly by favouring chromosomal translocations,
      aberrant hypermutation may represent the major contributor to lymphomagenesis.

PMID- 11460167
TI  - TAK1 is a ubiquitin-dependent kinase of MKK and IKK.
AB  - TRAF6 is a signal transducer that activates IkappaB kinase (IKK) and Jun amino
      terminal kinase (JNK) in response to pro-inflammatory mediators such as
      interleukin-1 (IL-1) and lipopolysaccharides (LPS). IKK activation by TRAF6
      requires two intermediary factors, TRAF6-regulated IKK activator 1 (TRIKA1) and
      TRIKA2 (ref. 5). TRIKA1 is a dimeric ubiquitin-conjugating enzyme complex
      composed of Ubc13 and Uev1A (or the functionally equivalent Mms2). This Ubc
      complex, together with TRAF6, catalyses the formation of a Lys 63 (K63)-linked
      polyubiquitin chain that mediates IKK activation through a unique proteasome
      independent mechanism. Here we report the purification and identification of
      TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex
      previously implicated in IKK activation through an unknown mechanism. We find
      that the TAK1 kinase complex phosphorylates and activates IKK in a manner that
      depends on TRAF6 and Ubc13-Uev1A. Moreover, the activity of TAK1 to phosphorylate
      MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63
      linked polyubiquitination. We also provide evidence that TRAF6 is conjugated by
      the K63 polyubiquitin chains. These results indicate that ubiquitination has an
      important regulatory role in stress response pathways, including those of IKK and
      JNK.

PMID- 11460168
TI  - A MAP kinase-dependent actin checkpoint ensures proper spindle orientation in
      fission yeast.
AB  - The accurate segregation of chromosomes at mitosis depends on a correctly
      assembled bipolar spindle that exerts balanced forces on each sister chromatid.
      The integrity of mitotic chromosome segregation is ensured by the spindle
      assembly checkpoint (SAC) that delays mitosis in response to defective spindle
      organisation or failure of chromosome attachment. Here we describe a distinct
      mitotic checkpoint in the fission yeast, Schizosaccharomyces pombe, that monitors
      the integrity of the actin cytoskeleton and delays sister chromatid separation,
      spindle elongation and cytokinesis until spindle poles have been properly
      oriented. This mitotic delay is imposed by a stress-activated mitogen-activated
      protein (MAP) kinase pathway but is independent of the anaphase-promoting complex
      (APC).

PMID- 11460169
TI  - Cdc6 cooperates with Sic1 and Hct1 to inactivate mitotic cyclin-dependent
      kinases.
AB  - Exit from mitosis requires the inactivation of mitotic cyclin-dependent kinases
      (CDKs). In the budding yeast, Saccharomyces cerevisiae, inactivation of CDKs
      during late mitosis involves degradation of B-type cyclins as well as direct
      inhibition of cyclin-CDK complexes by the CDK-inhibitor protein Sic1 (refs
      1,2,3). Several striking similarities exist between Sic1 and Cdc6, a DNA
      replication factor essential for the formation of pre-replicative complexes at
      origins of DNA replication. Transcription of both genes is activated during late
      mitosis by a process dependent on Swi5 (ref. 10). Like Sic1, Cdc6 binds CDK
      complexes in vivo and downregulates them in vitro. Here we show that Cdc6, like
      Sic1, also contributes to inactivation of CDKs during late mitosis in S.
      cerevisiae. Deletion of the CDK-interacting domain of Cdc6 does not inhibit the
      function of origins of DNA replication during S phase, but instead causes a delay
      in mitotic exit; this delay is accentuated in the absence of Sic1 or of cyclin
      degradation. By contributing to mitotic exit and inactivation of CDKs, Cdc6 helps
      to create the conditions that are required for its subsequent role in the
      formation of pre-replicative complexes at origins of DNA replication.

PMID- 11460171
TI  - The clinical profile of childhood optic neuritis.
AB  - PURPOSE: To report the clinical features and outcome of a series of children with
      optic neuritis. METHODS: We reviewed the medical records of patients up to 16
      years old with optic neuritis. Group 1 comprised children seen up to two weeks
      after the onset of visual loss; Group 2 comprised patients already harboring
      optic atrophy. RESULTS: There were 15 boys and 12 girls. The mean age was 10.9
      years. Bilateral optic neuritis occurred in 10. Optic disc pallor was found in
      35%, edema in 46%, and 19% had normal fundus. During follow-up visual acuity
      improved in all but one eye in Group 1, and in six of seven eyes in children in
      Group 2. Just one child converted to multiple sclerosis. CONCLUSIONS: This study
      shows that the clinical features of childhood optic neuritis differ from those
      observed in adults. In children it has a better visual outcome and a lower
      conversion rate to multiple sclerosis than in adults.

PMID- 11460172
TI  - Effect of lateralized epileptic discharges on the thought flow.
AB  - PURPOSE: Pauses in verbal expression of thought flow in patients with partial
      epilepsy was studied in order to achieve a best comprehension of brain
      interhemispheric influences. METHOD: We studied thirty nine patients with partial
      epileptic seizures and twenty four volunteers (control group). Free association
      of ideas was used as a method to establish the thought flow, starting with a
      stimulus word (subject name) that must be followed by spontaneous and consecutive
      word-phrase. Patients were instructed to say any thought that came to their minds
      without any kind of censoring. Subject responses were recorded through a PC
      keyboard and time intervals (pauses) between each word-phrase were processed by a
      software developed for this purpose. RESULTS: Time intervals reduction among
      associations in right lesional group were compared to left lesional, right non
      lesional and control groups. An increase of associative time intervals was
      observed in the right non-lesional group compared to left non-lesional group.
      CONCLUSIONS: We suggest a possible inhibitory inter-hemispheric function of the
      right hemisphere modulating verbal expression of the thought flow. Considering
      the hypothesis of the inter-hemispheric inhibition by the right hemisphere on
      left hemisphere, we admit that in epileptic patients with right hemispheric
      lesion there is an attenuation of the inter-hemispheric inhibition and an
      increase in thought flow, whereas in patients without a lesion but a paroxysmal
      epileptic activity in right temporal lobe there is an exacerbation of this
      inhibitory function and consequent reduction in the thought flow.

PMID- 11460173
TI  - Congestive heart failure and cognitive functioning amongst older adults.
AB  - BACKGROUND: Congestive heart failure is associated with decline in quality of
      life and, possibly, cognitive functions such as memory and attention. AIMS: The
      present study was designed to investigate the presence of cognitive impairment
      amongst patients with congestive heart failure (CHF). We hypothesised that CHF
      patients would have lower scores than elderly controls on general measures of
      cognitive functioning. METHODS AND RESULTS: We examined a sample of 50
      consecutive patients admitted to hospital with CHF functional class III/IV and a
      convenience sample of 30 older adults assessed at the outpatient service of
      geriatric medicine of a teaching hospital in Sao Paulo, Brazil. All subjects were
      interviewed with the Cambridge Examination for Mental Disorders of the Elderly
      (CAMDEX), as well as the neuropsychological battery of the CAMDEX (CAMCOG), Mini
      Mental State Examination (MMSE), Trail Making A and B, Digit Span, Digit Symbol,
      and Letter Cancellation Test. All CHF patients had left ventricular ejection
      fraction (EF) below 45% and all controls above 65%. The cognitive performance of
      CHF patients was significantly worse than controls for all cognitive assessments.
      Twenty-seven of 50 CHF patients had a MMSE total score lower than 24, compared
      with only 10/30 controls (p=0.073). Similarly, 36/49 and 9/30 CHF subjects and
      controls respectively had CAMCOG scores below 80 (p<0.001). Cognitive scores were
      significantly associated with EF, which was the most robust predictor of
      cognitive impairment according to the CAMCOG in a logistic regression model.
      CONCLUSION: Our results indicate that CHF is associated with significant levels
      of cognitive impairment and show that mental performance is, at least partly, a
      consequence of EF. Physicians should be prepared to assess the mental state of
      patients, as poor cognitive functioning may interfere with treatment compliance
      and management plan.

PMID- 11460174
TI  - A set of 400 pictures standardised for Portuguese: norms for name agreement,
      familiarity and visual complexity for children and adults.
AB  - The present article provides normative measures for 400 pictured objects
      (Cycowicz et al., 1997) viewed by Portuguese speaking Brazilian University
      students and 5-7 year-old children. Name agreement, familiarity and visual
      complexity ratings were obtained. These variables have been shown to be important
      for the selection of adequate stimuli for cognitive studies. Children's name
      agreement was lower than that of adults. The children also failed to provide
      adequate modal names for 103 concepts, rated drawings as less familiar and less
      complex, and chose shorter names for pictures. The differences in ratings between
      adults and children were higher than those observed in the literature employing
      smaller picture sets. The pattern of correlations among measures observed in the
      present study was consistent with previous reports, supporting the usefulness of
      the 400 picture set as a tool for cognitive research in different cultures and
      ages.

PMID- 11460175
TI  - Learning disabilities: analysis of 69 children.
AB  - With this article we intend to demonstrate the importance of evaluation and
      follow up of children with learning disabilities, through a multidisciplinary
      team. As well as to establish the need of intervention. We evaluate 69 children,
      from Aline Picheth Public School, in Curitiba, attending first or second grade of
      elementary school, through general and evolutionary neurological examination,
      pediatric checklist symptoms, and social, linguistic and psychological (WISC-III,
      Bender Infantile and WPPSI-figures) evaluation. The incidence was higher in boys
      (84,1%), familiar history of learning disabilities was found in 42%, and writing
      abnormalities in 56,5%. The most frequent diagnosis was attention deficit and
      hyperactivity disorder, in 39,1%. With this program, we aimed to reduce the
      retention taxes and stress the importance of this evaluation, and, if necessary,
      multidisciplinary intervention in the cases of learning disabilities.

PMID- 11460176
TI  - Neuropsychological and phonological evaluation in the Apert's syndrome: study of
      two cases.
AB  - This study evaluated two cases of Apert's syndrome, through phonological,
      cognitive, and neuropsychological instruments and correlated the results to
      complementary exams. In short, this study reveals the necessity of application of
      neuropsychological, cognitive and phonological evaluation and correlation of the
      results with complementary testings because significant differences can be
      present in the Apert's syndrome.

PMID- 11460177
TI  - Symptomatic muscle involvement in neurosarcoidosis: a clinicopathological study
      of 5 cases.
AB  - We report on the clinical course and histopathologic muscle alterations of five
      patients diagnosed with neurosarcoidosis, who underwent biopsy due to their
      muscle manifestations. The five patients were females and only one was less than
      40 years of age. Proximal muscle weakness was presented by all and only two
      patients complained of myalgia. Only normal values of serum muscle enzymes were
      detected. Electromyography revealed diverse findings such as normal, myopathic
      and neuropathic patterns. Granuloma was not present in one muscle biopsy. Two
      patients thoroughly recovered by taking only prednisone and one patient required
      a methotrexate addition for 3 months before becoming asymptomatic. The other two
      patients received azathioprine, one due to steroid side effects but without a
      satisfactory evolution, and the other to strengthen the prednisone regime, with
      excellent results.

PMID- 11460178
TI  - Bilateral pallidotomy for generalized dystonia.
AB  - OBJECTIVE: To evaluate the efficacy and safety of bilateral pallidotomies in five
      patients with generalized dystonia. BACKGROUND: Generalized dystonias are
      frequently a therapeutic challenge, with poor responses to pharmacological
      treatment. GPi (globus pallidus internus) pallidotomies for Parkinson's disease
      ameliorate all kinds of dyskinesias/dystonia, and recent studies reported a
      marked improvement of refractory dystonias with this procedure. METHODS: Five
      patients with generalized dystonias refractory to medical treatment were
      selected; one posttraumatic and four idiopathic. The decision to perform
      bilateral procedures was based on the predominant axial involvement in these
      patients. Dystonia severity was assessed with the Burke-Fahn-Marsden Dystonia
      Scale (BFM). Simultaneous procedures were performed in all but one patient, who
      had a staged procedure. They were reevaluated with the same scale (BFM) by an
      unblinded rater at 1, 2, 3, 30, 60, 90, 120 and 180 days post-operatively.
      RESULTS: The four patients with idiopathic dystonia showed a progressive
      improvement up to three months; the patient with posttraumatic dystonia relapsed
      at three months. One patient had a marked improvement, being able to discontinue
      all the medications. A mean decrease in the BFM scores of 52,58% was noted. One
      patient had a trans-operative motor seizure followed by a transient hemiparesis
      secondary to rack hemorrhage; other was lethargic up to three days after the
      procedure. CONCLUSIONS: Our results show that bilateral GPi pallidotomies may be
      a safe and effective approach to medically refractory generalized dystonias; it
      can also be speculated that the posttraumatic subgroup may not benefit with this
      procedure.

PMID- 11460179
TI  - Behaviour of oligodendrocytes and Schwann cells in an experimental model of toxic
      demyelination of the central nervous system.
AB  - Oligodendrocytes and Schwann cells are engaged in myelin production, maintenance
      and repairing respectively in the central nervous system (CNS) and the peripheral
      nervous system (PNS). Whereas oligodendrocytes act only within the CNS, Schwann
      cells are able to invade the CNS in order to make new myelin sheaths around
      demyelinated axons. Both cells have some limitations in their activities, i.e.
      oligodendrocytes are post-mitotic cells and Schwann cells only get into the CNS
      in the absence of astrocytes. Ethidium bromide (EB) is a gliotoxic chemical that
      when injected locally within the CNS, induce demyelination. In the EB model of
      demyelination, glial cells are destroyed early after intoxication and Schwann
      cells are free to approach the naked central axons. In normal Wistar rats,
      regeneration of lost myelin sheaths can be achieved as early as thirteen days
      after intoxication; in Wistar rats immunosuppressed with cyclophosphamide the
      process is delayed and in rats administered cyclosporine it may be accelerated.
      Aiming the enlightening of those complex processes, all events concerning the
      myelinating cells in an experimental model are herein presented and discussed.

PMID- 11460180
TI  - Teratogenic effects of lamotrigine on rat fetal brain: a morphometric study.
AB  - A study of the teratogenic activity of an antiepileptic drug - lamotrigine - was
      carried out in the brain of fetuses of rats who had received the drug. The dosage
      levels studied corresponded to four times the median effective dose (ED50) in
      rats. The drug was administered during the organogenesis period. Rats were
      sacrificed one day prior to term and fetuses were macroscopically examined,
      weighted and cephalic segments sectioned (Wilson technique), for histological
      study by stereological analysis, using Merz's grid for drawing and point counts.
      Cortex, subcortex, ependyma and lateral ventricles were analyzed. The same
      methodology was applied to the control group; data were compared with by the non
      parametric Mann-Whitney statistical analysis test. Results showed that fetuses of
      the experimental group had reduced body weight at birth, increased volume and
      diameter of the cerebral structure, increased density of the subcortical layer,
      and ventricle dilatation. Possible mechanisms of this teratogenicity were
      discussed.

PMID- 11460181
TI  - [Evaluation of brain ischemia by mitochondrial respiration: experimental model].
AB  - Brain ischemia occurs in several diseases. One of the critical factors for
      recovery of patients is the duration of the ischemic process. Brain activity
      depends on the energetic supply, it suggests that the study of mitochondrial
      function can be useful for evaluation of neuronal damage. The purpose of the
      present research was to study the mitochondrial respiration by occlusion of the
      left middle cerebral artery by intraluminal suture technique. Adults Wistar rats
      were subdivided in 4 groups: control, 15, 30 and 60 minutes of occlusion. Results
      showed that there was no significant difference between the group of 15 minutes
      and the control group. The group of 30 minutes had significant decrease of state
      III of mitochondrial respiration compared with control group. The group of 60
      minutes had significant decrease in state III and IV of mitochondrial respiration
      compared with control group. Mitochondrial respiration allowed an early and
      effective evaluation of focal ischemic process of the rat brain.

PMID- 11460182
TI  - [Use of lyophilized cellulose in peripheral nerve lesions with loss of
      substance].
AB  - Lyophilized cellulose was analysed to verify the degree of inflammatory reaction
      and axon realignment in the sciatic nerve after loss of neural substance. Ten
      mongrel dogs were divided into: Group 1 - 1 cm section of sciatic nerve which was
      replaced at lesion site; Group 2 nerve section without fragment replacement. The
      section site was involved with lyophilized cellulose. Group 3 -1 cm fragment
      section sutured epineurally. Motor response started at eighth week. Moderate
      fibrotic reaction to cellulose was seen in Group 1 and 2 animals. Groups 1 and 3
      showed coaptation between the nerve and nerve graft with ongoing axons. In Group
      2, 1 dog showed regrowth of axons through the empty space. It was concluded that
      lyophilized cellulose caused moderate fibrous reaction when implanted in
      peripheral nerve lesions with loss of substance; it can act as envelop protection
      in those lesions mainly if a neural graft is inserted.

PMID- 11460183
TI  - [Volumetric determination of cerebral infarction in the acute phase using skull
      computed tomography without contrast: comparative study of 3 methods].
AB  - The determination of lesion volumes in acute cerebral Infarction (CI) has
      important prognostic and therapeutic implications. Three different methods 
      computerised technique, linear planimetry and the A.B.C/2 formula - were compared
      in 27 patients using non-contrast computerised tomography (CT) made at hospital
      admission (first 48 hours following symptom onset). Two independent observers
      performed the measurements. The Intra-class correlation coefficients (ICCs) were
      determined. The three methods exhibited high interrelation. There was a close
      correlation between the linear planimetry as well as the ABC/2 formula and the
      computerised method with ICCs of 0.94-0.95 and 0.835-0.90 respectively. Linear
      planimetry and the ABC/2 formula were also highly correlated, with ICCs between
      0.97 and 0.99. In conclusion, the computerised method is probably the most
      accurate. Linear planimetry and the ABC/2 formula are also reliable, however. The
      A.B.C/2 formula should be applied routinely to CI volume determination based on
      its low cost and fast calculation.

PMID- 11460184
TI  - [Magnetic resonance angiography of intracranial aneurysms: comparative study with
      cerebral angiography].
AB  - We studied by magnetic resonance angiography and cerebral angiography 41 patients
      with 55 aneurysms confirmed by surgery. The MR angio detected 52 aneurysms with
      sensibility of 94.5% and the cerebral angiography detected 53 aneurysms with
      sensibility of 96.3%. For being non invasive, more quickly and less expensive MR
      angio may substitute vascular angiography in the diagnosis of intracranial
      aneurysms and prognosis of the subarachnoid hemorrhage

PMID- 11460185
TI  - [Clinical characterization of vascular dementia: retrospective evaluation of an
      outpatient sample].
AB  - OBJECTIVE: to analyze the clinical features and associated morbidity in a group
      of patients with vascular dementia (VD). METHODS: we retrospectively evaluated 25
      patients with diagnosis of VD, based on the State of California Alzheimers
      Disease Diagnostic and Treatment Centers (ADDTC) criteria. Clinical and
      neuroimaging data and laboratory test results were obtained for the
      characterization of the sample. RESULTS: the mean age was 68.7 +/- 14.6 years
      (64.0% men), with mean educational level of 5.2 +/- 4.4 years. Sudden onset of
      symptoms was observed in 48.0% of patients and stepwise deteriorating and
      fluctuating courses being observed in 4.0% and 16% respectively. Focal neurologic
      deficits were the first symptom in 48.0%, with focal deficits being observed in
      80% on examination. The main morbidity were: hypertension (92.0%);
      hypercholesterolemia (64.0%); coronary heart disease (40.0%); smoking (40.0%);
      hypertriglyceridemia (36.0%); diabetes mellitus (32.0%); Chagas' disease (8.0%).
      CONCLUSIONS: we observed strong association between VD and hypertension and
      hypercholesterolemia. The observation of two patients presenting Chagas' disease
      suggests that this endemic condition may be considered a possible regional risk
      factor.

PMID- 11460186
TI  - [Oropharyngeal dysphagia in the myotonic dystrophy: phonoaudiological evaluation
      and nasofibrolaryngoscopical analysis].
AB  - We here in present twenty myotonic dystrophy of Steinert patients with the main
      objective to evaluate and classify the oropharyngeal swallowing by the
      phonoaudiological clinical and nasofibrolaryngoscopical analysis. The age of the
      patients varied from 12 to 53 years, being 13 male and 7 female. The mean data:
      (1) statistically significant relation between the phonoaudiological clinical
      evaluation and nasofibrolaryngoscopical one; (2) stomatognatical system disorders
      present in 100%; (3) swallowing disorders present in 95%, when clinically
      evaluated, and in 70% when evaluated by the nasofibrolaryngoscopy; (4) higher
      difficulty to swallow consistent feed; (5) stomatognatical muscles very altered,
      pharyngeal phase disorders, cough after swallowing, antecedents of pneumonia and
      complaints of chewing/swallowing presented statistically significant correlation
      with severity of the sickness. The analysis were able to evaluate statical and
      functionally the involved structures in the swallowing, having got to take part
      of the routine of attendance to the patients with myotonic dystrophy of Steinert.

PMID- 11460187
TI  - [Comorbidity in children and adolescents with attention-deficit disorder:
      preliminary results].
AB  - Thirty-four children and adolescents with ages from 6 to 16 years having a
      diagnosis of attention-deficit hyperactivity disorder (ADHD)according to DSM-IV
      criteria were examined. Psychiatric comorbidity was evaluated through a standard
      questionnaire given to parents. There was a significant comorbidity (85,7%) in
      the sample, oppositional-defiant disorder (20,6%) and conduct disorder (39,2%)
      being the most common comorbid diagnosis. At least two diagnosis other than ADHD
      could be found in 57% of the sample. Major depression was seen in four cases and
      anxiety states (generalized anxiety disorder, separation anxiety and phobias)
      were seen in 34.3% of the sample. Comorbidity modifies prognosis in a significant
      way and may suggest specific therapeutic interventions according to each case.
      Frequent comorbidity may suggest the need for diagnostic interviews that covers
      other psychiatric disorders.

PMID- 11460188
TI  - [Rett syndrome: retrospective and prospective study of 28 patients].
AB  - From November 1982 to May 1999, 28 children with Rett syndrome were followed-up
      for a medium period of 6 years and 2 months. Regression of developmental
      milestones started at the age between 5 and 20 months. Nineteen cases of typical
      Rett syndrome had uneventful pre and perinatal periods, loss of previously
      acquired purposeful hand skills, mental and motor regression and developed hand
      stereotypies; sixteen had head growth deceleration and 12 gait apraxia. Nine
      patients were atypical cases, 2 formes frustres, 2 congenital, 3 with early
      seizure onset, 1 preserved speech and 1 male. Epilepsy was present in 21
      patients, predominantly partial seizures and the drug of choice was carbamazepine
      (15 patients). In the initial evaluation most patients were distributed on Stages
      II and III and on follow-up on Stages III and IV. Three children died.

PMID- 11460189
TI  - [The neuropathology of neonatal period: analysis of 1616 autopsies].
AB  - The lesions of the central nervous system represent an important cause of morbid
      mortality in the neonatal period. This is due to the vulnerability of the brain
      to several adverse conditions during gestation and after birth. This study
      analyses the prevalence and pattern of central nervous system lesions in neonates
      autopsied at Hospital de Clinicas - Curitiba. There were 5743 pediatric autopsies
      performed in the Sector of Anatomic Pathology from 1960 to 1995 with 2049 cases
      corresponding to death during neonatal period. These later autopsies were
      reviewed and all cases with central nervous system lesions were selected and
      classified according to sex, age and pattern of central nervous system lesion.
      The central nervous system was affected in 1616 (78,87%) of neonatal autopsies
      and there was predominance of intracerebral hemorrhages (73,39%), congenital
      malformations (4,27%) and infections (3,59%). The hypoxic hemorrhages are the
      most prevalent central nervous system lesions in the neonatal period, affecting
      mainly premature babies. There was predominance of central nervous system
      malformations in the female neonates.

PMID- 11460190
TI  - [Metopic suture craniosynostosis: sodium valproate teratogenic effect. Case
      report].
AB  - OBJECTIVE: the aim of this report is to warn that sodium valproate used during
      pregnancy can produce craniosynostosis in the newborn, particularly
      trigonocephaly. METHOD: we describe a case of trigonocephaly in a six month-old
      girl, daughter of a young non-smoker couple, whose mother had used phenobarbital
      100 mg daily and sodium valproate 500 mg twice daily during the whole pregnancy.
      We also review current literature about this topic. RESULT: bone sclerosis over
      the metopic suture was confirmed during surgery. Bibliographical review yields
      previous reports on valproate teratogenicity, mainly determining metopic suture
      craniosynostosis. CONCLUSION: sodium valproate used during pregnancy can produce
      craniosynostosis by teratogenic effect, specially trigonocephaly (premature
      fusion of metopic suture).

PMID- 11460191
TI  - Naso-ethmoid schwannoma with intracranial extension: case report.
AB  - Intranasal schwannomas are rare lesions, specially when they present with an
      intracranial extension. The fifth case in the medical literature of a naso
      ethmoid schwannoma with extension into the anterior cranial fossa is presented.
      The magnetic resonance findings and the details of the combined intracranial /
      transfacial operative approach used are described. The possible origin and the
      clinical characteristics of this rare lesion are reviewed.

PMID- 11460192
TI  - Infrasellar craniopharyngioma: case report.
AB  - We report a case of infrasellar craniopharyngioma in a 34 year-old woman who
      presented with progressive headache and diplopia. Computed tomographic and
      magnetic resonance images showed a heterogeneous tumor originating from the
      sphenoid bone with ethmoid sinus and sella turcica extension. A sublabial
      rhinoseptal transsphenoidal surgery was performed. Craniopharyngiomas with
      infrasellar development are very rare. Infrasellar craniopharyngioma is uncommon,
      thirty-five cases has been reported in literature. The embryology, clinical
      features and radiographic investigation of these tumors are discussed.

PMID- 11460193
TI  - [Spinal cord ganglioglioma: case report].
AB  - Gangliogliomas are rare tumors of the CNS, representing only 2.7-3.8% of primary
      tumors of the CNS, and the intramedullary location accounts 7.6-14.3% of cases.
      The main goal of treatment is the total resection, preserving as much as possible
      the patients neurological function. Adjuvant therapy as radiotherapy is reserved
      to cases of progression of disease after surgery or in such lesion with more
      aggressive biological behavior. In this article we report the case of a patient
      with a intramedullary ganglioglioma involving spinal levels T5 to T10, who was
      operated in our service, and we review the literature analyzing various aspects,
      including the modalities of treatment which can be used in this kind of lesion.

PMID- 11460194
TI  - [Cerebrovascular chronic occlusive disease (moyamoya): case report].
AB  - A six years old boy, Japanese descendant, born in the city of Sao Paulo, Brazil,
      arrived to the hospital with sudden loss of muscular strength at the left side of
      the body. The cranial computerised tomography showed a right fronto-parietal
      ischemia and the digital angiography by caterism of femural artery, confirmed the
      diagnosis of brain obstructive chronic vascular disease(moyamoya). We have
      checked out in the literature that previous superior aerial ways infection,
      frequently precede the neurological manifestations. Such symptoms are in
      agreement with the mentioned case. This has suggested the hypothesis of
      inflammatory-immunologic origin of this disease.

PMID- 11460195
TI  - [Epidural spinal cavernous angioma: case report].
AB  - Epidural spinal cavernous angiomas account for approximately 4% of all spinal
      epidural tumors. More recently the diagnosis has become more frequent due to
      refinement of imaging modalities. We describe a 50-year-old woman with a spinal
      epidural cavernous angioma at L1-L2, which was successfully surgical treated.
      Clinical picture, imaginology and treatment of this entity is reviewed.

PMID- 11460196
TI  - [Cerebral arterial aneurysm in a child with acquired immunodeficiency syndrome:
      case report].
AB  - Cerebral aneurysmal arteriopathy of the circle of Willis is an uncommon
      manifestation of acquired human immunodeficiency virus (HIV) infection and up to
      now only 15 cases have been published in the literature. For this reason we add
      our experience of this rare case, and review the most important aspects related
      to this entity. The patient is a 6 year old male with perinatal transmitted AIDS,
      tetraparethic, developed symptoms characterized by episodes of dystonic postures.
      The computed tomography of the brain showed aneurismal arteriopathy of the circle
      of Willis. He had a previous normal examination. The review of the literature
      shows the pathological abnormalities of the affected vessels are mainly medial
      fibrosis, with destruction of the internal elastic lamina and intimal
      hyperplasia. The etiology for the vasculitis is unknown. Varicela zoster virus,
      as well as HIV by itself, can be related to the physiopathology of the
      vasculitis. On conclusion, it can be said that although uncommon, such
      complications are of great importance by the fact that the patients with vascular
      aneurismal arteriopathy are in high risk for vascular accidents, and once a
      diagnosis was made, death occurs in less than 6 months, according to the
      literature.

PMID- 11460197
TI  - [Pseudomigraine with CSF pleocytosis: intermittent measurement of the
      intracranial pressure. Case report].
AB  - Pseudomigraine with pleocytosis is a self-limited and rather benign disorder,
      characterized by recurrent bouts of migrainous headaches, associated to focal
      neurological symptoms and to cerebrospinal fluid abnormalities. We have submitted
      an individual with pseudomigraine to three lumbar punctures. The first and the
      third lumbar punctures, carried out during symptomatic periods, revealed a
      cerebrospinal fluid with aseptic lymphomonocytic pleocytosis, and an opening
      pressure of 400 and 440 mmH2O, respectively. The cerebrospinal fluid pressure
      measured during an asymptomatic period was normal (190 mmH20). Although the
      underlying mechanisms of this disorder remain elusive, there is some evidence
      that suggests an involvement of autoimmune mechanisms leading to a reduction of
      the cerebral blood flow, similar to that seen in the cortical spreading
      depression. In this report, we raise the possibility of a contributory role to be
      played by the elevated cerebrospinal fluid pressure on the pathophysiology of
      this disorder.

PMID- 11460198
TI  - [Brain vascular disease presenting as first manifestation of temporal arteritis:
      report of two cases].
AB  - Brain vascular disease as the first presentation of temporal arteritis is
      unusual. We present two cases in which the diagnosis emerged from the anamnesis.
      A 54 years old woman has had a left cerebral infarct 3 months ago. She was
      getting better when severe visual loss occurred and the family decided to get a
      second opinion. The patient have had right hemiparesis, aphasia and a left visual
      disturbance in the first episode; now she had severe bilateral visual
      disturbance. We suspected temporal arteritis was the etiology. HSR was 97 mm and
      fundoscopy disclosed severe ischemic optic neuritis. A 75 years old man presented
      Wallenberg syndrome. The history disclosed temporal headache and the examination
      showed inflammation in temporal artery. HSR was 70 mm and biopsy confirmed the
      diagnosis. "Tecnolatry" is affecting medical practice; it's necessary to put back
      in the center the clinical sovereignty.

PMID- 11460199
TI  - [Aicardi syndrome: case report].
AB  - We report a case of Aicardi syndrome in a female child with 2 month old, ocular
      abnormalities "chorioretinal lacunae", flexion in spasms, hipsarrhythmic "split
      brain", callosal agenesis referred to Service of Neuropediatric and
      Neurophysiology of Base Hospital of Sao Jose do Rio Preto, SP, Brazil.

PMID- 11460200
TI  - [Diagnosis and treatment of associated epilepsy and psychogenic pesudoepileptic
      seizures: case report].
AB  - We report on a case of a 26 year old patient with seizures since the age of 13,
      who was sent to our service for differential diagnosis between epilepsy and
      psychogenic pesudoepileptic seizures. Both diagnoses were confirmed and she was
      operated for the resection of an occipital cystic tumour, that was considered
      responsible for her epileptic seizures, which remitted after surgery. Her
      psychogenic pseudoepileptic seizures persisted, but, after 4 months of a
      comprehensive psychological treatment, including behavioural therapy and family
      orientation remission set in. The authors stress the need for multiple diagnostic
      and therapeutic procedures and the participation of a specialised
      multidisciplinary team.

PMID- 11460201
TI  - [Benign paroxysmal positioning vertigo].
AB  - Benign paroxysmal positioning vertigo is a frequent vestibular disorder. With a
      simple maneuver one can easily diagnose this condition and treatment is based on
      liberatory maneuvers. On this review the pathogenesis, the clinical features and
      different maneuvers are briefly discussed.

PMID- 11460202
TI  - Energy expenditure after 2- to 3-hour elective surgical operations.
AB  - Energy expenditure was measured by indirect calorimetry in 17 adult patients (8
      women and 9 men) before surgery, 4 hours immediately after surgery, and 24 hours
      late after surgery in patients undergoing elective surgery of small-to-medium
      scope. MATERIAL AND METHODS: The total duration of surgery ranged from 2 to 3
      hours. Repeated measures were performed on the same patient, so that each patient
      was considered to be his/her own control. All patients received a 5% dextrose
      solution (2000 mL/day) throughout the postoperative period. RESULTS: Men showed a
      reduction in CO2 production during the immediately after surgery period (257+/-42
      mL/min) compared to before surgery (306+/-48 mL/min) and late after surgery
      (301+/-45 mL/min); this reduction was not observed in women. Energy expenditure
      was also lower in men during immediately after surgery (6.6 kJ/min). None of the
      other measurements, including substrate oxidation, showed significant
      differences. CONCLUSION: Therefore, elective surgery itself cannot be considered
      an important trauma that would result in increased energy expenditure. According
      to this study, it is not necessary to prescribe an energy supply exceeding basal
      expenditure during the immediate after-surgery period. The present results
      suggest that the energy supply prescribed during the postoperative period after
      elective surgery of small-to-medium scope should not exceed 5-7 kJ/min, so the
      patient does not receive a carbohydrate overload from energy supplementation.

PMID- 11460203
TI  - Cost of drugs manufactured by the university hospital--role of the Central
      Pharmacy.
AB  - The hospital pharmacy in large and advanced institutions has evolved from a
      simple storage and distribution unit into a highly specialized manipulation and
      dispensation center, responsible for the handling of hundreds of clinical
      requests, many of them unique and not obtainable from commercial companies. It
      was therefore quite natural that in many environments, a manufacturing service
      was gradually established, to cater to both conventional and extraordinary
      demands of the medical staff. That was the case of Hospital das Clinicas, where
      multiple categories of drugs are routinely produced inside the pharmacy. However,
      cost-containment imperatives dictate that such activities be reassessed in the
      light of their efficiency and essentiality. METHODS: In a prospective study, the
      output of the Manufacturing Service of the Central Pharmacy during a 12-month
      period was documented and classified into three types. Group I comprised drugs
      similar to commercially distributed products, Group II included exclusive
      formulations for routine consumption, and Group III dealt with special demands
      related to clinical investigations. RESULTS: Findings for the three categories
      indicated that these groups represented 34.4%, 45.3%, and 20.3% of total
      manufacture orders, respectively. Costs of production were assessed and compared
      with market prices for Group 1 preparations, indicating savings of 63.5%. When
      applied to the other groups, for which direct equivalent in market value did not
      exist, these results would suggest total yearly savings of over 5 100 000 US
      dollars. Even considering that these calculations leave out many components of
      cost, notably those concerning marketing and distribution, it might still be
      concluded that at least part of the savings achieved were real. CONCLUSIONS: The
      observed savings, allied with the convenience and reliability with which the
      Central Pharmacy performed its obligations, support the contention that internal
      manufacture of pharmaceutical formulations was a cost-effective alternative in
      the described setting.

PMID- 11460204
TI  - Gastric and colorectal cancer mortality in an urban and industrialized area of
      Brazil.
AB  - PURPOSE: To study the gastric and colorectal cancer mortalities and their
      relation to the urban-industrialization in Baixada Santista, located in the
      southeastern region of Brazil. METHODS: Selected from the registries of the State
      System of Data Analysis Foundation (SEADE) were 1105 deaths due to gastric cancer
      (ICD 153 - 154) and 690 due to colorectal cancer (ICD 151) that occurred from
      1980 to 1993 in males, above 10 years of age, residing in Baixada Santista. For
      each of these types of cancer, the standardized mortality rates, age-adjusted by
      world population in the 1960s, for 4 industrialized and 4 non-industrialized
      urban communities in that region were calculated. The ratios among those rates
      were calculated in order to compare the mortality in the periods 1980 - 93, 1980 
      1986, and 1987 - 1993. RESULTS: Standardized mortality rates for colorectal
      cancer were significantly higher in industrialized area, with ratios of 1.6 [95%
      CI 1.22 - 2.29], 1.6 [95% CI 1.2 - 2.0], and 1.6 [95% CI 1.3 - 2.0] in the
      periods 1980 - 86, 1987 - 1993 and 1980 - 93, respectively. Gastric cancer did
      not show any statistical difference between the industrialized and non
      industrialized areas, but there was a significant decrease in BS from the period
      1980 - 1986 to 1987 - 1993. CONCLUSIONS: The significant elevation of colorectal
      cancer mortality in the industrialized area could be related to exposure to
      numerous carcinogens such as aromatic hydrocarbon, organic-chloride, metals, and
      industrial-port dust present in the region. Alternatively, the non-significant
      difference in gastric cancer between industrialized and non-industrialized areas
      and significant decrease in the last few years could be predominately reflecting
      the advances in the quality of life in urban areas. These results require further
      case-control studies that could help with the analysis of the associations among
      cancer and environmental factors (occupational, urban-industrial, habit, and life
      condition) and genetic susceptibility.

PMID- 11460205
TI  - Chemotherapy versus best supportive care in stage IV non-small cell lung cancer,
      non metastatic to the brain.
AB  - Stage IV non-small cell lung cancer is a fatal disease, with a median survival of
      14 months. Systemic chemotherapy is the most common approach. However the impact
      in overall survival and quality of life still a controversy. OBJECTIVES: To
      determine differences in overall survival and quality of life among patients with
      stage IV non-small cell lung cancer non-metastatic to the brain treated with best
      supportive care versus systemic chemotherapy. PATIENTS: From February 1990
      through December 1995, 78 eligible patients were admitted with the diagnosis of
      stage IV non-small cell lung cancer. Patients were divided in 2 groups: Group A
      (n=31 - treated with best supportive care ), and Group B (n=47 - treated with
      systemic chemotherapy). RESULTS: The median survival time was 23 weeks (range 5 -
      153 weeks) in Group A and 55 weeks (range 7.4 - 213 weeks) in Group B (p=0.0018).
      In both groups, the incidence of admission for IV antibiotics and need of blood
      transfusions were similar. Patients receiving systemic chemotherapy were also
      stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and
      those receiving other combination regimens (platinum derivatives associated with
      other drugs, n=22). Patients receiving mytomycin, vinblastin, and cisplatinum,
      n=25 had a higher incidence of febrile neutropenia and had their cycles delayed
      for longer periods of time than the other group. These patients also had a
      shorter median survival time (51 versus 66 weeks, p=0.005). CONCLUSION: In
      patients with stage IV non-small cell lung cancer, non-metastatic to the brain,
      chemotherapy significantly increases survival compared with best supportive care.

PMID- 11460206
TI  - Necrotizing fasciitis in a newborn infant: a case report.
AB  - We report the case of a one-day-old newborn infant, female, birth weight 1900 g,
      gestational age 36 weeks presenting with necrotizing fasciitis caused by E. coli
      and Morganella morganii. The newborn was allowed to fall into the toilet bowl
      during a domestic delivery. The initial lesion was observed at 24 hours of life
      on the left leg at the site of the venipuncture for the administration of
      hypertonic glucose solution. Despite early treatment, a rapid progression
      occurred resulting in a fatal outcome. We call attention to the risk presented by
      this serious complication in newborns with a contaminated delivery, and highlight
      the site of the lesion and causal agents.

PMID- 11460207
TI  - [Evaluation of secondary bacterial infection's influence on the course of
      cutaneous leishmaniasis in Corte de Pedra, Bahia].
AB  - In order to study the prevalence of secondary bacterial infection in ulcerated
      lesions and its relationship to the healing process, 84 leishmaniotic patients
      were evaluated. Diagnosis of the secondary infection was made by bacterial
      aerobic culture of peripheral tissue specimen of the ulcer. All patients received
      antimonial therapy during 20 days and washed their ulcers with common soap. Cases
      were composed mainly of adolescent and adult farmer patients with single lesions.
      The evaluated ulcers were encountered on legs and feet in 47.6%. Secondary
      bacterial infection was found in 45/83 (54.2%), and was more frequent in lesions
      located below the knee. Staphylococcus aureus predominated (89%). The ulcers'
      healing process, evaluated in 79 patients one month after finishing treatment,
      was not influenced by the secondary bacterial infection.

PMID- 11460208
TI  - Human parvovirus B19 infection in HIV-positive patients.
AB  - Parvovirus B19 infects predominantly erythroid cells, leading to transient
      inhibition of erythropoiesis. Immunocompromised patients may be unable to produce
      neutralizing antibodies and may develop severe chronic anemia. Epidemiological
      studies done on Niteroi population showed that B19 infection occurs periodically
      in late spring and summer. We report a study from 55 HIV infected patients
      attending an infectious diseases outpatient clinic in this city during a 5-month
      period in which B19 circulation was well documented. All patients were under anti
      retroviral therapy. No anti-B19 IgM was found, but a high prevalence of IgG anti
      B19 (91%) was observed. In six patients, B19 DNA was found by dot-blot
      hybridization techniques, but this was not confirmed by PCR. None of these 6
      patients manifested anemia and only one had CD4 cell count below 200 x 10(7)/L.
      We conclude that persistent infection causing anemia is an infrequent finding in
      our HIV positive patients under drug therapy.

PMID- 11460209
TI  - Frequency of Mycoplasma hominis and Ureaplasma urealyticum infections in women
      with systemic lupus erythematosus.
AB  - Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) have been detected in the
      urine of women with systemic lupus erythematosus (SLE). We evaluated the presence
      of these mycoplasma in the endocervix of women presenting SLE. A total of 40 SLE
      patients (mean age 40.2 years), and 51 healthy women (mean age 30.9 years), were
      studied. Endocervical swabs were cultured in specific liquid media for MH or UU,
      detected by a quantitative color assay, and considered positive at >10(3)
      dilutions. Statistical analysis was performed using the two-tailed Fisher test.
      UU was detected in 52.5 % of patients and in 11.8% of controls (p= 0.000059). MH
      was detected in 20% of patients and 2% controls (p=0.003905). Both mycoplasmas
      were detected in 7.3% patients and 0% controls (p<0.000001). The results reported
      here corroborate the association of the mycoplasma infection and SLE. Thus, these
      agents may stimulate the production of autoreactive clones.

PMID- 11460210
TI  - [Leishmaniasis urbanization and low diagnosis capacity in the Metropolitan Region
      of Belo Horizonte].
AB  - During the period from 1994 to 1999 cutaneous leishmaniasis was reported in 32
      (89%) out of 36 municipalities in the Metropolitan Region of Belo Horizonte,
      Brazil, of which one (2,8%) municipality was classified as a very high risk area,
      16 (44,5%) as high risk, seven (19,4%) as moderate risk areas and 12 (33,3%) as
      low risk. From 1994 to 1995, visceral leishmaniasis was reported in six (16%)
      municipalities whereas in 1998 - 1999 this number increased to 15 (42%). Annual
      numbers of cases during 1994 to 1999 were 30, 53, 64, 53 and 84, respectively. In
      19 (61.3%) municipalities no reference center for the diagnosis of the infection
      was available, so that most of the patients (80%) were referred to Belo
      Horizonte. Twelve (39%) municipalities have a center for leishmaniasis
      evaluation, however in only eight (67%) of these basic specific diagnostic tests
      were available. Rapid and extensive increase of leishmaniasis associated with low
      diagnosis capacity has been observed in the metropolitan area of Belo Horizonte.

PMID- 11460211
TI  - Ecology of phlebotomine sandflies (Diptera, Psychodidae) in Brazilian Atlantic
      Forest.
AB  - The phlebotomine sandfly fauna of a primary forest reserve at Morretes (eastern
      Parana State) was studied, using CDC-like light traps, one night per month, at
      canopy and ground level, between April 1995 and March 1996. A total of 3,106
      insects were collected, identified as belonging to nine species. Lutzomyia
      ayrozai and Lu.geniculata were predominant, seven other species also being
      present. Monthly mean temperature, rainfall and the temperature of the collection
      night significantly influenced the numbers of Lu. ayrozai while the two first
      factors influenced the numbers of Lu. geniculata, besides the collected
      quantities of females of the two species. The influence of the factors on Lu.
      ayrozai numbers was more immediate than in those of Lu. geniculata. Numbers of
      both species and of the females of Lu. geniculata collected in different seasons,
      but not at the different heights, varied significantly. Differences between the
      behaviour of Lu. ayrozai in Morretes and in other regions could be attributed to
      environmental differences and/or to regional variations in the species, which
      could constitute species complexes. Hourly variations of collections were
      different in the species and seasons.

PMID- 11460212
TI  - [Severe forms of leptospirosis: clinical, demographic and environmental aspects].
AB  - Characteristics of 1,016 patients hospitalized with leptospirosis in the Hospital
      Couto Maia, Salvador, BA, Brazil, between 1993 and 1997 are described. Higher
      pluviometric precipitation was related to an increase in the number of
      hospitalizations during the following month. Males corresponded to 81.1%
      (824/1,016) of these; mean age was 35.7+/-15.4 years. Almost 94% (778/829) of the
      829 patients with information about race were black or mulatto (mixed race). For
      ages 18 years or above, almost 93% had not completed high school level. The mean
      incubation period was estimated as 6.3+/-3.9 days. Average duration of symptoms
      was 6.1+/-2.4 days. Hemorrhagic events corresponded to 14.3% (145/1,016). The
      case-fatality rate among 1,009 patients that were not transferred was 14.2%
      (143/1,009). Renal failure was the attributable cause of death in 76.2%
      (109/143). The data indicate that leptospirosis is closely related to lower
      socioeconomic levels, and that higher pluviometric precipitation antecedes the
      outbreaks.

PMID- 11460213
TI  - [Epidemiology of dengue in Salvador-Bahia, 1995-1999].
AB  - Since 1981, Brazil has registered dengue epidemic and simultaneous circulation of
      the DEN-1 and DEN-2 serotypes in over 2,700 municipalities. In Salvador- Bahia,
      located in the Northeastern region of the Country, two epidemic outbreaks
      occurred in the years of 1995 and 1996, with further endemic spread of the
      disease. This study analyses the incidence of the virosis within this municipal
      area, from 1995 to 1999, considering, among other variables, its distribution in
      the Sanitary Districts and density of Aedes aegypti. Registers of notified cases
      and the city's Vectorial Control Program were used as data source. The incidence
      rate of notified cases of dengue in 1995 and 1996, which were 691.4 and 393.5 per
      100,000 inhabitants, respectively, decreased to 65 per 100,000 inhabitants in
      1998. In the poorer Sanitary Districts, this index reached figures of over 800
      per 100,000 inhabitants. The Premise Index for Aedes aegypti reached 54.1% in one
      of the Districts. Bearing in mind the relevance of the re-emergence of dengue in
      the world, the authors discuss the possible factors which condition the virus
      introduction, its epidemiological presentation over the course of four years, and
      the effectiveness of the vectorial combat (eradication) program.

PMID- 11460214
TI  - [Presence of Loxosceles similis Moenkhaus, 1898 (Araneae, Sicariidae) in Serra da
      Bodoquena, State of Mato Grosso do Sul, Brazil].
AB  - The venom of Loxosceles spiders causes dermonecrotic lesion and induces
      complement-dependent intravascular haemolysis that characterizes a severe
      systemic effect. In Brazil, L. gaucho, L. intermedia and L. laeta, present in the
      anthropic environment, have been pointed out as the most important agents of the
      loxoscelism. Besides these species there are others that, by predominating in the
      natural environment, have not been evaluated regarding human health risk, as in
      the case of Loxosceles similis. The development of a research project in
      Bodoquena Range, for ecological observation and identification of insects of
      medical interest, enabled the capture of Loxosceles similis specimens in the
      "Pitangueiras" cave and "Lago Azul" cave, in Bodoquena Range, municipality of
      Bonito, State of Mato Grosso do Sul, Brazil. The objectives of this study were to
      define the parameters for identification, environmental features of the habitat
      of this species, as well as an update of its geographical distribution.

PMID- 11460215
TI  - [Freshwater snails of the Campus of Manguinhos, Oswaldo Cruz Foundation, Rio de
      Janeiro, RJ].
AB  - A survey of freshwater gastropods of the Campus of Manguinhos, Fundacao Oswaldo
      Cruz, Rio de Janeiro, was carried out during the last two years aiming to compare
      the current species with those found at the beginning of this century. Among 18
      breeding sites in 880,000m2 of the surveyed area, 13 showed the following
      species: Antillorbis nordestensis; Biomphalaria glabrata; Biomphalaria straminea;
      Lymnaea columella; Melanoides tuberculatus; Physa cubensis; Pomacea glauca and
      Pomacea lineata. Notably, Biomphalaria tenagophila reported by Lutz in 1918, had
      disappeared and B. straminea and the Asiatic thiarid M. tuberculatus had been
      introduced. No specimens infected with Schistosoma mansoni were found.

PMID- 11460216
TI  - [Neurocysticercosis].
AB  - It has been estimated that 50 million people are infected with the
      taeniasis/cysticercosis complex in the world today and that 50,000 die each year.
      It also appears that 350,000 individuals remain infected in Latin America. In
      Ribeirao Preto, Brazil, neurocysticercosis has been identified in 7.5% of the
      patients admitted to a ward specialized in the treatment of neurologic diseases.
      Its clinical manifestations comprise seizures, intracranial hypertension,
      cysticercotic meningitis, psychiatric symptoms, apoplectic or endarteritic form,
      and spinal cord syndrome. Lethality of neurocysticercosis varies from 16.4% to
      25.9%. Diagnosis is dependent on the results of computed tomography of the brain
      and examination of the cerebrospinal fluid. Lately, albendazole in association
      with steroids has been elected the treatment of choice for neurocysticercosis. In
      the authors' opinion, compulsory notification of cases and preventive measures
      should be implemented. In Brazil, in the absence of a centralized program of
      control, regional initiatives should be stimulated, keeping in mind WHO's advice:
      "Think globally, act locally".

PMID- 11460217
TI  - [Dermatophytic pseudomycetoma: report of a case caused by Trichophyton
      tonsurans].
AB  - A case of dermatophytic pseudomycetoma, in a patient with a history of recurrent
      lesions in the scalp, for over two years, is reported. Histopathological
      examination of the affected tissues revealed the mycelial aggregates or
      pseudogranules characteristic of the disease. Cultures of fresh tissues samples
      detected a fungus identified as Trichophyton tonsurans. Additional examinations
      failed to demonstrate lesions of tinea capitis, a probable source of the deep
      infection. Dermatophytic pseudomycetoma is an extremely rare form of
      dermatophytosis, and the rarity of such cases is the motive for the present
      communication.

PMID- 11460218
TI  - Hepatocyte metaplasia in experimental chagasic pancreatitis: preliminary report.
AB  - Beginning the study of chronic pathologic changes in pancreas of hamsters
      experimentally infected with Trypanosoma cruzi Vic strain, hepatocyte metaplasia
      was observed in one animal from infected group. This is the first report of
      oncocytes in Chagas' disease, which could be due to aberrant regenerative
      response to pancreas inflammatory process.

PMID- 11460219
TI  - [Serologic survey for leptospirosis and brucellosis in patients from the rural
      area of Guaraci County, Parana State, Brazil].
AB  - The present study evaluated patients that were attended at the Health Center of
      Guaraci Municipality, Parana State, Brazil. Three (2.6%) patients were
      leptospirosis positive from a total of 115 samples. No significant statistical
      differences were observed for risk factors. There was no positive test for
      brucellosis.

PMID- 11460220
TI  - [Occurrence of canine visceral leishmaniasis in an agricultural settlement in the
      State of Mato Grosso do Sul, Brazil].
AB  - During previous research on phlebotomine fauna in a settlement of the Brazilian
      National Agrarian Reform Institute (INCRA) on the Bodoquena Range, Mato Grosso do
      Sul State, Brazil, dogs were observed with clinical aspects suggestive of
      visceral leishmaniasis. A serological survey to leishmaniasis in 97 dogs, by
      indirect immunofluorescence test, showed 23 (23.7%) serum positive dogs. Samples
      of the parasites were identified as Leishmania (Leishmania) chagasi.

PMID- 11460222
TI  - Letter from the International Liver Transplantation Society president.

PMID- 11460223
TI  - MELD and PELD: application of survival models to liver allocation.

PMID- 11460224
TI  - Long-term follow-up of patients diagnosed with alcohol dependence or alcohol
      abuse who were evaluated for liver transplantation.
AB  - The selection of patients with cirrhosis and the diagnosis of alcohol dependence
      or abuse who have a long-term high probability of abstinence after orthotopic
      liver transplantation (OLT) may enhance patient survival and outcomes. The aim of
      this study is to identify factors that would predict which patients would consume
      alcohol after OLT. Sixty-one patients with a history of alcohol dependence or
      abuse underwent OLT from June 1989 to June 1994 and were followed up monthly for
      a median of 6.9 years after OLT (range, 2.5 to 9.3 years). Survival analysis
      techniques (Cox proportional hazard model) were used to identify patients at high
      risk for recidivism. Recidivism occurred in 12 of 61 patients (20%) after OLT
      during follow-up. Noncompliance, with a relative hazard of 20.9 (95% confidence
      interval [CI], 5.6 to 78.3; P <.001), and personality disorder, with a relative
      hazard of 6.0 (95% CI, 1.9 to 18.7; P =.002), independently predicted recidivism
      among patients who underwent OLT. These data indicate that specific behaviors and
      psychiatric diagnoses can be used to select patients at high risk for drinking
      alcohol before and after OLT.

PMID- 11460225
TI  - Disease recurrence after living liver transplantation for primary biliary
      cirrhosis: a clinical and histological follow-up study.
AB  - We describe the recurrence of primary biliary cirrhosis (PBC) in recipients of
      living liver transplants. We are not aware of similar previous reports. Because
      most donors for living liver transplantation (LLT) are blood relatives with close
      HLA matches, the recurrence of PBC in transplant recipients might offer
      additional insights in the pathogenesis of the condition. We studied 6 women
      (age, 29 to 61 years) with PBC who survived LLT for at least 1 year. Tests for
      antimitochondrial autoantibody (AMA), antipyruvate dehydrogenase complex-E2,
      immunoglobulin G (IgG) anti-M2, and IgM anti-M2 had confirmed the diagnosis.
      Donors were blood relatives in 5 instances, and one donor who was not a blood
      relative still had multiple HLA matches with the recipient. After LLT, we
      observed a decrease in AMA titers, but within 1 year, these titers increased
      again in 5 of the 6 patients to pre-LLT levels or greater. Immunoblotting
      analysis of the anti-M2 protein profile failed to show loss of bands and showed
      new bands in 3 of 6 patients. Histologically, strong evidence of recurrent PBC
      was found in 2 patients, and findings compatible with PBC were present in 1
      additional patient. All 6 patients are doing well, without symptoms of recurrent
      PBC (median time post-LLT, 35.5 months; range, 12 to 50 months).

PMID- 11460226
TI  - Recurrent primary biliary cirrhosis.

PMID- 11460227
TI  - Allocation of transplantable organs: do people want to punish patients for
      causing their illness?
AB  - Some people believe patients with alcoholic cirrhosis should not receive equal
      priority for scarce transplantable organs. This may reflect a belief that these
      patients (1) are personally responsible for causing their own illnesses, (2) have
      poor transplant prognoses, or (3) are unworthy because they have engaged in
      socially undesirable behavior. We explore the roles that social desirability and
      personal responsibility have in people's judgments about transplant allocation.
      We presented prospective jurors with 4 scenarios, asking them to distribute 100
      transplantable organs among 2 groups of 100 patients each. In each scenario, 1
      group of patients, but not the other, was described as having a history of
      unhealthy behavior (alcohol or cigarette use) associated with a poorer prognosis.
      In some scenarios, alcohol or cigarette use was said to cause the organ failure.
      In others, it only contributed to the patients' transplant prognosis. We also
      obtained self-reports of subjects' own smoking status. Subjects allocated
      significantly fewer than half the organs to those with unhealthy behaviors and
      worse prognoses (33%; P <.001), but the specific behavior (alcohol versus
      cigarette use) was not significantly associated with subjects' allocation
      choices. Significantly fewer organs were allocated to patients with behavior
      responsible for causing their diseases than to other patients (P <.0001).
      Subjects who never smoked discriminated the most and current smokers
      discriminated the least against patients with a history of unhealthy behavior (P
      <.0001). The public's transplantation allocation preferences are influenced by
      whether patients' behaviors are said to have caused their organ failure.

PMID- 11460228
TI  - Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease.
AB  - Although nonalcoholic steatohepatitis (NASH) has generally been considered a
      benign condition, the increasing prevalence and severity of obesity has
      heightened concerns about the frequency with which NASH progresses to end-stage
      liver disease. The aim of this study is to determine the frequency, clinical
      features, and posttransplantation history of decompensated liver disease
      secondary to NASH. The frequency of NASH as a cause of end-stage liver disease
      was prospectively determined in patients evaluated for liver transplantation.
      NASH was considered to be the primary cause of liver disease in patients who had
      histological evidence of steatohepatitis and in whom chronic liver diseases other
      than NASH were excluded. Posttransplantation histological characteristics were
      also determined in patients with NASH and compared with those of patients with
      pretransplantation diagnoses of cholestatic liver diseases, alcoholic disease,
      and hepatitis C. Of 1,207 patients evaluated for liver transplantation during the
      study period, 31 patients (2.6%) had NASH as the primary cause of liver disease.
      In the same period, 546 liver transplantations were performed, 16 of which (2.9%)
      were for end-stage disease secondary to NASH. Posttransplantation steatosis was
      seen in 60% of transplant recipients with NASH versus 5% of those with
      cholestatic disease, 15% of those with alcoholic disease, and 15% of those with
      hepatitis C. Steatohepatitis recurred in 33% of transplant recipients with NASH,
      with progression to cirrhosis in 12.5%. NASH can progress to end-stage liver
      disease in a minority of affected patients and was the primary cause of liver
      disease in 2.9% of patients evaluated for liver transplantation at our center.
      Recurrence of steatosis and NASH is frequent and can be severe after liver
      transplantation.

PMID- 11460229
TI  - Influence of extracorporeal porcine liver perfusion on nonhuman primates:
      minimizing hemolysis improves subsequent survival.
AB  - The aim of this study is to detect and analyze risk factors of direct cross
      circulation between porcine liver and nonhuman primates before a clinical
      application of extracorporeal liver perfusion (ECLP) as a liver-assist method.
      Porcine livers were perfused with baboon blood in an ECLP system. Six healthy
      baboons were directly connected to the ECLP system with continuous prostaglandin
      E(1) administration. Cross-circulation was terminated in the following
      circumstances: (1) hepatic arterial or portal perfusion pressures elevated to 200
      or 60 mm Hg, respectively; (2) massive exudative bleeding from the graft surface;
      or (3) bile output decreased to less than 5 microL/h/g of liver weight. In case
      1, cross-circulation was continued for 10 hours. Severe macroscopic hemolysis
      occurred, and serum hemoglobin (s-Hb) concentration reached a peak of 47 mg/dL.
      The baboon died of acute renal failure 2 days later. Histological study of the
      perfused porcine liver showed marked microthrombi formation. In 3 of the later 5
      cases, cross-circulation was discontinued when mild macroscopic hemolysis was
      observed. The duration of the 5 cross-circulations was maximally 6 hours (mean,
      4.4 +/- 1.2 [SD] hours). Mean s-Hb concentration in the 5 cases was elevated to
      14.8 +/- 5.8 mg/dL at the end of cross-circulation and decreased to the baseline
      level within 24 hours. These 5 baboons survived without organ dysfunction or
      immunologic disturbance. When severe hemolysis is avoided, direct cross
      circulation using the ECLP system can be achieved without serious complications
      in nonhuman primates.

PMID- 11460230
TI  - Does tacrolimus offer virtual freedom from chronic rejection after primary liver
      transplantation? Risk and prognostic factors in 1,048 liver transplantations with
      a mean follow-up of 6 years.
AB  - Tacrolimus has proven to be a potent immunosuppressive agent in liver
      transplantation (LT). Its introduction has led to significantly less frequent and
      severe acute rejection. Little is known about the rate of chronic rejection (CR)
      in primary LT using tacrolimus therapy. The aim of the present study is to
      examine the long-term incidence of CR, risk factors, prognostic factors, and
      outcome after CR. The present study evaluated the development of CR in 1,048
      consecutive adult primary liver allograft recipients initiated and mostly
      maintained on tacrolimus-based immunosuppressive therapy. They were evaluated
      with a mean follow-up of 77.3 +/- 14.7 months (range, 50.7 to 100.1 months). To
      assess the impact of primary diagnosis on the rate and outcome of CR, the
      population was divided into 3 groups. Group I included patients with hepatitis C
      virus (HCV)- or hepatitis B virus (HBV)-induced cirrhosis (n = 312); group II
      included patients diagnosed with primary biliary cirrhosis (PBC), primary
      sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH; n = 217); and group
      III included patients with all other diagnoses (n = 519). Overall, 32 of 1,048
      patients (3.1%) developed CR. This represented 13 (4.1%), 12 (5.5%), and 7
      patients (1.3%) in groups I, II, and III, respectively. The relative risk for
      developing CR was 3.2 times greater for group I and 4.3 times greater for group
      II compared with group III. This difference was statistically significant (P
      =.004). The incidence of acute rejection and total number of acute rejection
      episodes were significantly greater in patients who developed CR compared with
      those who did not (P <.0001). Similarly, the mean donor age for CR was
      significantly older than for patients without CR (43.0 v 36.2 years; P =.02).
      Thirteen of the 32 patients (40.6%) who developed CR retained their original
      grafts for a mean period of 54 +/- 25 months after diagnosis. Seven patients
      (21.9%) underwent re-LT, and 12 patients (38.3%) died. Serum bilirubin levels and
      the presence of arteriopathy, arterial loss, and duct loss on liver biopsy at the
      time of diagnosis of CR were significantly greater among the 3 groups of
      patients. In addition, patient and graft survival for group I were significantly
      worse compared with groups II and III. We conclude that CR occurred rarely among
      patients maintained long term on tacrolimus-based immunosuppressive therapy. When
      steroid use is controlled, the incidence of acute rejection, mean donor age, HBV-
      and/or HCV-induced cirrhosis, or a diagnosis of PBC, PSC, or AIH were found to be
      predictors of CR. Greater values for serum bilirubin level, duct loss,
      arteriopathy, arteriolar loss, and presence of HCV or HBV were found to be poor
      prognostic factors for the 3 groups; greater total serum bilirubin value (P =.05)
      was the only factor found to be significant between patients who had graft loss
      versus those who recovered.

PMID- 11460231
TI  - Influence of tumor characteristics on the outcome of liver transplantation among
      patients with liver cirrhosis and hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) may recur after liver transplantation (LT), mainly
      in patients with multinodular and large tumors. However, factors predictive of
      outcome after LT in patients with small tumors remain ill defined. We
      investigated which factors were related to mortality or tumor recurrence among 47
      liver transplant recipients with liver cirrhosis and HCC and compared them with
      107 patients with liver cirrhosis without tumor who underwent LT in the same
      period. Patients with HCC were older (P <.001), more frequently had cirrhosis of
      a viral origin (P <.001), and had lower Child-Pugh scores (P <.001) than patients
      without tumor. Survival of patients with and without tumor was not significantly
      different (P =.20). Among patients with HCC, those with lower recurrence-free
      survival rates had liver cirrhosis of a viral origin, vascular invasion, bilobar
      disease, and tumor-node-metastasis (TNM) stage IV. At multivariate analysis, the
      only factor associated with mortality or recurrence was TNM stage IV (P =.02).
      Our results suggest that in patients with HCC and TNM stage IV, LT might be
      contraindicated.

PMID- 11460232
TI  - Life-threatening hypophosphatemia after right hepatic lobectomy for live donor
      adult liver transplantation.
AB  - Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only
      once after liver resection for tumor and was associated with a significant
      increase in postoperative complications. Hypophosphatemia is associated with
      reversible cardiac dysfunction, hypoventilation, and impaired immunity. The
      purpose of this study was to determine the incidence of hypophosphatemia after
      elective right hepatic lobectomy for live donor adult liver transplantation
      (LDALT), investigate the associated complication rate and surgical outcome of
      live liver donors, and determine the efficacy of prospective treatment with
      phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30
      donors who provided 30 right-lobe grafts between December 1998 and January 2000
      was performed. Of the initial 18 live liver donors (group 1), 10 donors were
      treated with TPN that contained slightly more (35 +/- 8 mmol/d) than the
      recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on
      postoperative day 1. The last 12 donors (group 2) were prospectively studied and
      administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All
      donors in group 1 developed hypophosphatemia that was either life threatening
      (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1
      mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8%
      developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30%
      developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest
      that hypophosphatemia is a universal event after LDALT and may have contributed
      to the observed complications in this study. Repletion of phosphorus at twice the
      RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity.
      Institutions performing LDALT should carefully monitor live liver donors for
      hypophosphatemia and correct abnormal phosphate levels. Additional studies are
      needed to determine whether more aggressive parenteral repletion can prevent
      postoperative hypophosphatemia and thus improve outcomes.

PMID- 11460233
TI  - Unusual presentation of porphyria post-liver transplantation.

PMID- 11460234
TI  - Recurrent portopulmonary hypertension after liver transplantation: management
      with epoprostenol and resolution after retransplantation.
AB  - We report a case of portopulmonary hypertension in which the pulmonary
      hypertension resolved after initial orthotopic liver transplantation.
      Portopulmonary hypertension recurred when the transplanted liver failed and again
      resolved after a second liver transplantation. Intravenous epoprostenol was
      administered perioperatively to control the pulmonary hypertension in both
      instances.

PMID- 11460235
TI  - Stenosis of the suprahepatic inferior vena cava as a complication of transjugular
      intrahepatic portosystemic shunt in Budd-Chiari patients.
AB  - We report 2 patients with Budd-Chiari (BC) syndrome secondary to thrombogenic
      conditions who underwent transjugular intrahepatic portosystemic shunt (TIPS)
      placement because of refractory ascites and impending liver failure. After TIPS
      placement, there was marked symptomatic relief and improvement in liver function,
      but the courses of both patients were complicated by the development of an
      inferior vena cava (IVC) syndrome caused by segmental stenosis of the
      suprahepatic IVC just at the outflow jet of the TIPS at 11 and 9 months later.
      One patient underwent liver transplantation, and the other patient, caval
      angioplasty and stenting. Stenosis of the IVC represents an unrecognized
      complication of TIPS in patients with BC syndrome.

PMID- 11460236
TI  - Successful outcome after transplantation of a donor liver with focal nodular
      hyperplasia.
AB  - Because of the increasing gap in the number of patients awaiting organ
      transplantation and the supply of organ donors, reevaluation of donor criteria is
      an important issue in clinical transplantation. It has become necessary to make
      maximal use of the currently available donor pool. We describe a case of
      successful orthotopic liver transplantation in a 57-year-old man with Laennec's
      cirrhosis using a liver containing an 8-cm focal nodular hyperplasia (FNH) lesion
      involving segments II and III and the caudate lobe. The donor liver was procured
      from a 46-year-old woman declared brain dead after a subarachnoid hemorrhage.
      Definitive pathological diagnosis was made at laparotomy by obtaining a Tru-cut
      (Allegiance Health Care Inc, Toronto, Ontario, Canada) core biopsy specimen. The
      recipient operation was performed uneventfully except for bleeding from the
      biopsy site. The patient did well postoperatively and was discharged on
      tacrolimus, mofetil mycophenolate, and prednisone therapy. He continues to thrive
      2(1/2) years posttransplantation with no change in the size of the lesion. In
      well-selected donors, FNH should not be a contraindication for use in
      transplantation. However, FNH must be differentiated from hepatocellular adenoma.
      Although FNH has a benign course with little propensity for bleeding and almost
      no malignant potential, hepatic adenoma is reported to have a 15% to 33% chance
      of bleeding and rupture with a well-documented potential for neoplastic
      degeneration, making the liver unsuitable for donation.

PMID- 11460237
TI  - Hepatopulmonary syndrome and extrahepatic vascular abnormalities.

PMID- 11460238
TI  - Transplant legislation: ethical and practical issues in liver allocation--The
      case of Switzerland.
AB  - Ethical and practical issues relating to liver allocation have been discussed in
      many countries. Several governments, including the United States, have attempted
      over the past few years to impose new legislation, which has resulted in virulent
      debates among individual centers, organ procurement agencies, states, and various
      groups of interest. This report discusses the current ongoing legislative process
      in Switzerland. In 1999, the people of Switzerland voted to develop transplant
      legislation. This reflected the need to regulate poorly defined practices to
      adapt to the rapid progress within the field of transplantation. The main issue
      facing the Swiss transplant community is whether new legislation will allow
      medical evolution in organ allocation criteria without creating regulations that
      may become outdated with time. In addition, public debate has been shown to have
      a negative impact on organ donation, thus emphasizing an ever-present penury in
      cadaveric allografts. This article discusses these issues within the context of
      liver transplantation in Switzerland and also raises the uniform ethical and
      practical constraints placed on the medical transplant community in the face of
      an organ shortage.

PMID- 11460239
TI  - Response to Piotr Kalicinski.

PMID- 11460240
TI  - Alcohol production from cheese whey permeate using genetically modified
      flocculent yeast cells.
AB  - Alcoholic fermentation of cheese whey permeate was investigated using a
      recombinant flocculating Saccharomyces cerevisiae, expressing the LAC4 (coding
      for beta-galactosidase) and LAC12 (coding for lactose permease) genes of
      Kluyveromyces marxianus enabling for lactose metabolization. Data on yeast
      fermentation and growth on cheese whey permeate from a Portuguese dairy industry
      is presented. For cheese whey permeate having a lactose concentration of 50 gL(
      1), total lactose consumption was observed with a conversion yield of ethanol
      close to the expected theoretical value. Using a continuously operating 5.5-L
      bioreactor, ethanol productivity near 10 g L(-1) h(-1) (corresponding to 0.45 h(
      1) dilution rate) was obtained, which raises new perspectives for the economic
      feasibility of whey alcoholic fermentation. The use of 2-times concentrated
      cheese whey permeate, corresponding to 100 gL(-1) of lactose concentration, was
      also considered allowing for obtaining a fermentation product with 5% (w/v)
      alcohol.

PMID- 11460241
TI  - On-line determination of animal cell concentration.
AB  - A new approach for the indirect determination of cell concentration in the case
      of nonconstant metabolic rates has been developed. The specific glucose-uptake
      rate was shown to be nonconstant in batch cultures of free suspended and
      immobilized CHO SSF3 cells. Time-independent models correlating the specific rate
      to the limiting substrate concentration were established, thus providing a
      continuous determination of the specific rate through on-line measurement of the
      limiting substrate. The method could be applied to determine on-line cell
      concentration in both free suspended and immobilized cell cultures. Results were
      verified off-line by crystal violet nuclei counting. The predicted cell
      concentration was in very good agreement with the off-line reference during the
      whole exponential-growth phase, until the specific glucose-uptake rate tended to
      zero.

PMID- 11460242
TI  - Chloroperoxidase-catalyzed enantioselective oxidations in hydrophobic organic
      media.
AB  - Chloroperoxidase from Caldariomyces fumago, a peroxidase that performs P450-like
      chemistry, was immobilized via covalent attachment into polyurethane foam as well
      as conjugated with a surfactant or polymer via colyophilization. The resulting
      preparations catalyzed enantio- and regioselective oxidations in hydrophobic
      organic media with tert-butyl hydroperoxide as the oxidant. Dried PUR-foam
      immobilized CPO mediated the selective oxidation of indole to 2-oxindole
      (regioselectivity: 99%) in water-saturated isooctane or 1-octanol. Thioanisole
      was converted into the corresponding (R)-sulfoxide (ee > 99%) in isooctane
      medium. The complexes of CPO with sodium octadecylsulphate or ethyl cellulose
      mediated the oxidation of thioanisole in water-immiscible organic media with
      variable enantioselectivity due to radical side-reactions. In the presence of
      alpha-tocopherol, acting as radical scavenger, the (R)-sulfoxide was formed with
      ee > 90%. The effect of the water activity on the catalytic activity of the
      complexes was investigated. The CPO complexes likewise mediated the
      regioselective oxidation of indole into 2-oxindole in water-saturated isooctane
      or 1-octanol and its kinetics were investigated. The reaction suffered from
      substrate inhibition when carried out in isooctane.

PMID- 11460243
TI  - Immobilization of enzymes on PTFE surfaces.
AB  - Membranes and powders prepared from PTFE (polytetrafluorethylene) were
      investigated for their potential use as multifunctional supports for enzymes. The
      obtained bioactive materials are valuable for the construction of biosensors and
      enzyme reactors. To allow covalent coupling of enzymes to PTFE, the surface of
      the material was treated with elementary sodium followed by oxidation with ozone
      or hydrogen peroxide.%Derivatization steps were optimized in order to achieve
      highest enzyme loading and short reaction times. Alliinase (EC 4.4.1.4) and L
      lactic dehydrogenase (EC 1.1.1.27) were chosen as model enzymes and were either
      immobilized by covalent coupling or fixed indirectly by a sugar-lectin binding.
      For the latter method, the sugar mannan was bound to the membrane surface as an
      anchor for layers of the lectin concanavalin A and the alliinase. Highest
      alliinase loading was achieved at 0.2 microg x cm(-2). Immobilization of
      alliinase via the lectin concanavalin A and a bifunctional epoxide gave the best
      long-term stability.%L-Lactic dehydrogenase was most sufficiently immobilized by
      using benzoquinone as spacer. These procedures show several advantages: 1)
      enzymes can be immobilized under physiological conditions, 2) an enzyme
      multilayer can be achieved, and 3) protein layers are renewable.

PMID- 11460244
TI  - Chemoenzymatic synthesis of sucrose-containing aromatic polymers.
AB  - A chemoenzymatic approach was developed to prepare sucrose-containing aromatic
      polymers. The protease from Bacillus licheniformis catalyzed the
      transesterification of sucrose with a diester of terephthalic acid in pyridine to
      give the mono- and diester products. At 45 degrees C, >70% of sucrose was
      consumed after 1 day and sucrose diester began to form after 6 days when >95% of
      sucrose had been converted to sucrose monoester. The final yield of sucrose
      diester after 20 days was 13.8%. The sucrose monoester was identified as sucrose
      1'-terephthalate and the diester products consisted of sucrose 6,1'
      diterephthalate and sucrose 6',1'-diterephthalate in a ratio of 2:1. The sucrose
      diester products were polymerized with ethylene-glycol and ethylene-diamine to
      give poly(ethylene-terephthalate) and poly(ethylene-terephthalamide), with
      sucrose contained in the polymer backbone. The polycondensation reactions were
      carried out in dimethylsulfoxide (DMSO) at 70 degrees C using zinc acetate as a
      catalyst. The sucrose-containing polyester and polyamide were obtained at 65%
      yield for 24 h and at 73% yield for 12 h, respectively. End-group analysis of the
      polymers by (13)C-NMR or (1)H-NMR in DMSO provided a number average molecular
      weight of 3200 and 4300 Da, respectively. Structural analyses of the polymers
      were performed with (1)H-NMR, (13)C-NMR, and FTIR. On the basis of (13)C-NMR,
      acylation of the C1', C6, and C6' hydroxyls were maintained in the polymer
      backbones.

PMID- 11460245
TI  - Kinetic modeling and simulation of in vitro transcription by phage T7 RNA
      polymerase.
AB  - This study provides a mathematical model of T7 RNA polymerase (T7 RNAP) kinetics
      under in vitro conditions targeted at application of this model to simulation of
      dynamic transcription performance. A functional dependence of transcript
      synthesis rate is derived based on: (a) essential reactant concentrations,
      including T7 RNAP and its promoter, substrate nucleotides, and the inhibitory
      byproduct inorganic pyrophosphate; (b) a distinction among vector characteristics
      such as recognition sequences regulating transcription initiation and
      termination, respectively; and (c) specific properties of the nucleotide sequence
      including both transcript length and nucleotide composition. Inactivation
      kinetics showed a half-life of T7 RNAP activity of 50 min under the conditions
      applied in vitro using the isolated enzyme. Model parameters and their precision
      are estimated using dynamic simulation and nonlinear regression analysis. The
      particular novelty of this model is its capability to incorporate linear genomic
      sequence information for simulation of nonlinear in vitro transcription kinetics.

PMID- 11460246
TI  - Horseradish peroxidase catalyzed degradation of industrially important dyes.
AB  - Horseradish peroxidase (HRP) is known to degrade certain recalcitrant organic
      compounds such as phenol and substituted phenols. Here, for the first time we
      have shown HRP to be effective in degrading and precipitating industrially
      important azo dyes. For Remazol blue, the enzyme activity was found to be far
      better at pH 2.5 than at neutral pH. In addition, Remazol blue acts as a strong
      competitive inhibitor of HRP at neutral pH. Horseradish peroxidase shows broad
      substrate specificity toward a variety of azo dyes. Kinetic constants (K(m)(app)
      and V(max)(app)) for two different dyes have been determined. In addition to
      providing a systematic analysis of the potential of HRP in degradation of dyes,
      this study opens up a new area on exploration of commercial dyes as inhibitors of
      enzymes. 2001 John Wiley & Sons, Inc.

PMID- 11460247
TI  - Optimization of production and downstream processing of the almond beta
      glucosidase-mediated glucosylation of glycerol.
AB  - This article describes the synthesis of glyceryl glucoside from glycerol and
      glucose with almond beta-glucosidase as the catalyst. A yield of 54% (0.45
      mmol/g) was obtained. The influence of the enzyme stability, the water
      concentration, and the water activity on the glucoside yield were determined. A
      molar fraction-based equilibrium constant of 2.4 +/- 0.6 was found, with which
      the glucoside yield could be calculated for all possible combinations of initial
      substrate and water fractions in the reaction mixture. A model was used to
      optimize the glucoside yield while minimizing one of the substrate concentrations
      at equilibrium. This straightforward model gives a good prediction of the
      measured glucoside yield, according to a parity plot.

PMID- 11460248
TI  - Characterization of an oxygen-dependent inducible promoter, the nar promoter of
      Escherichia coli, to utilize in metabolic engineering.
AB  - The nar promoters, whose transcription is maximally induced under microaerobic
      conditions in the presence of nitrate ion, were characterized in fed-batch
      culture to determine whether they can be used for metabolic engineering, by which
      overall production of valuable chemicals can be increased. For this purpose, we
      tested whether the expression level of a reporter gene, the lacZ gene from the
      nar promoter, could be maintained constant throughout the induction period by
      manipulation of dissolved oxygen (DO) levels at a given nitrate ion
      concentration. First, E. coli was grown under aerobic conditions (DO 80%) to
      absorbance at 600 nm (OD(600)) of 35, then the nar promoter was induced by
      reduction of DO to different levels, combined with different frequencies and
      duration of alternating microaerobic and aerobic conditions throughout the entire
      induction period. For a wild-type nar promoter (pMW61) in a mutant host E. coli
      with a mutation in the narG gene on the chromosome of the host (RK5265), it was
      possible to maintain production of beta-galactosidase activity per cell (specific
      beta-galactosidase activity) at a constant rate at 5000, 10,000, 15,000, and
      20,000 Miller units, using different combinations of nitrate ion concentrations
      (0.1%, 0.5%, and 1%) and DO levels. In addition, it was possible to maintain
      production of specific beta-galactosidase activity at a constant rate at about
      10,000 Miller units in the absence of nitrate ion when a nitrate-independent nar
      promoter (pMW618) in the narL(-) mutant of the W3110 E. coli strain (W3110narL(
      )) was used. Based on these results, we conclude that the nar promoter system
      provides a convenient expression system for metabolic engineering as well as for
      maximal production of recombinant proteins under conditions of fed-batch culture.

PMID- 11460249
TI  - Dynamics of spheroid self-assembly in liquid-overlay culture of DU 145 human
      prostate cancer cells.
AB  - The in vitro self-assembly of multicellular spheroids generates highly organized
      structures in which the three-dimensional structure and differentiated function
      frequently mimic that of in vivo tissues. This has led to their use in such
      diverse applications as tissue regeneration and drug therapy. Using Smoluchowski
      like rate equations, herein we present a model of the self-aggregation of DU 145
      human prostate carcinoma cells in liquid-overlay culture to elucidate some of the
      physical parameters affecting homotypic aggregation in attachment-dependent
      cells. Experimental results indicate that self-aggregation in our system is
      divided into three distinct phases: a transient reorganization of initial cell
      clusters, an active aggregation characterized by constant rate coefficients, and
      a ripening phase of established spheroid growth. In contrast to the diffusion
      controlled aggregation previously observed for attachment-independent cells, the
      model suggests that active aggregation in our system is reaction-controlled. The
      rate equations accurately predict the aggregation kinetics of spheroids
      containing up to 30 cells and are dominated by spheroid adhesive potential with
      lesser contributions from the radius of influence. The adhesion probability
      increases with spheroid size so that spheroid-spheroid adhesions are a minimum of
      2.5 times more likely than those of cell-cell, possibly due to the upregulation
      of extracellular matrix proteins and cell-adhesion molecules. The radius of
      influence is at least 1.5 to 3 times greater than expected for spherical geometry
      as a result of ellipsoidal shape and possible chemotactic or Frohlich
      interactions. Brownian-type behavior was noted for spheroids larger than 30
      microm in diameter, but smaller aggregates were more motile by as much as a
      factor of 10 for single cells. The model may improve spheroid fidelity for
      existing applications of spheroids and form the basis of a simple assay for
      quantitatively evaluating cellular metastatic potential as well as therapies that
      seek to alter this potential.

PMID- 11460250
TI  - Comparative analysis of two controlled proliferation strategies regarding product
      quality, influence on tetracycline-regulated gene expression, and productivity.
AB  - Overexpression of the cyclin-dependent kinase inhibitor p27 and exposure to low
      temperature (30 degrees C) represent two strategies to establish controlled
      proliferation processes for production of therapeutic proteins using Chinese
      hamster ovary (CHO) cells. Here we analyze the effect of growth inhibition on the
      quality of the human model glycoprotein SEAP (secreted alkaline phosphatase) for
      both strategies in monoclonal CHO-derived cell lines. Separation of purified SEAP
      samples using two-dimensional gel electrophoresis showed that production by
      proliferation-controlled CHO cultures did not alter the overall integrity of the
      product. Further, oligosaccharide profiles were compared using HPEC-PAD analysis.
      No differences were detectable between SEAP profiles obtained from p27 growth
      arrested and proliferating cultures. However, production at 30 degrees C led to a
      significant increase in the degree of sialylation, an effect that is generally
      considered beneficial for the in vivo efficacy of protein therapeutics. In the
      production context presented here, SEAP expression is controlled by the
      tetracycline- (tet) repressible gene regulation system. Here we show low
      temperature-induced upregulation of the tetracycline-dependent transactivator
      (tTA). This induction has been shown by Northern blot analysis to occur at the
      mRNA level and is independent of the promoters driving the transactivator. We
      also describe a novel bottleneck in productivity at low temperature found in p27
      growth-arrested CHO cells cultivated at 30 degrees C.

PMID- 11460251
TI  - Alteration of the growth rate and lag time of Leuconostoc mesenteroides NRRL
      B523.
AB  - Bacterial profile modification is an important enhanced oil recovery technique
      used to direct injected water into a reservoir's low permeability zone containing
      trapped crude oil. During water flooding, the use of bacteria to plug the high
      permeability water zone and divert flow into the oil-bearing low-permeability
      zone will have a significant economic impact. However, during the field
      implementation of bacterial profile modification, the rapid growth of bacteria
      near the injection well bore may hinder the subsequent injection of growth media
      so that profile modification of the reservoir occurs only in the immediate
      vicinity of the well bore. By slowing the growth rate and prolonging the lag
      phase, the onset of pore-space plugging may be delayed and the biologically
      active zone extended deep into the reservoir. High substrate loading, high pH
      values, and the addition of the growth inhibitors sodium dodecylsulfate and
      sodium benzoate have been used in combination to alter the growth characteristics
      of Leuconostoc mesenteroides NRRL-B523 grown in batch conditions. The highest
      sucrose concentration used in these studies, 500 g/L, produced lag times 12-fold
      greater than the slowest lag times achieved at low sucrose concentrations. When
      L. mesenteroides was grown in media containing 500 g/L sucrose, an alkaline pH
      value threshold was found above which bacteria did not grow. At this threshold pH
      value of 8.1, an average lag time of 200 h was observed. Increasing the
      concentration of sodium benzoate had no effect on lag time, but reduced the
      growth rate until the threshold concentration of 0.6%, above which bacteria did
      not grow. Last, it was found that a solution of 0.075 mM sodium dodecylsulfate in
      media containing 15 g/L sucrose completely inhibited bacterial growth.

PMID- 11460252
TI  - Protein secretion biotechnology using Streptomyces lividans: large-scale
      production of functional trimeric tumor necrosis factor alpha.
AB  - We evaluated the feasibility of large-scale production of biopharmaceuticals
      expressed as heterologous polypeptides from the Gram-positive bacterium
      Streptomyces lividans. As a model protein we used murine tumor necrosis factor
      alpha (mTNFalpha). mTNFalpha fused C-terminally to the secretory signal peptide
      of the subtilisin-inhibitor protein from Streptomyces venezuelae. Under
      appropriate fermentation conditions, significant amounts of mature mTNFalpha (80
      120 mg/L) can be recovered from spent growth media. Efficient downstream
      processing allowing rapid purification of mTNFalpha from culture supernatants was
      developed. Importantly, the protein is recovered from the spent growth medium in
      its native trimeric state as judged by biophysical analysis. Further, mTNFalpha
      secreted by S. lividans is significantly more active in an in vitro apoptosis
      tissue culture assay than a corresponding polypeptide produced in Escherichia
      coli. This pilot study provides the first validation of S. lividans protein
      secretion as an alternative bioprocess for large-scale production of oligomeric
      proteins of potential therapeutic value.

PMID- 11460253
TI  - Quantitative screening method for hydrolases in microplates using pH indicators:
      determination of kinetic parameters by dynamic pH monitoring.
AB  - The presented pH-dyn assay serves as a versatile tool for screening enzymatically
      catalyzed reactions consuming or producing acids. The method is based on material
      balances of substrates and products. Ion balances relate concentrations of acids
      and bases to pH. pH-changes caused by the enzymatically catalyzed reaction in a
      well-defined buffer system are recorded by light-absorption measurements of a pH
      indicator. Kinetic parameters are estimated by fitting the modeled pH changes to
      the experimentally observed ones. The enzymatically catalyzed hydrolysis of 4
      nitrophenol is used as a model system. A pH indicator, bromothymol blue, is used
      to monitor the reaction progress. The reaction is monitored until the limiting
      substrate is completely consumed. This allows the estimation of the parameters of
      the Michaelis-Menten kinetics, K(M) and k(cat), in a single run. The results
      agree well with conventional spectrophotometric experiments and values reported
      in literature. Around pH 7, environmental CO(2) influences pH. Carbon dioxide
      influence was included in the model. Thus it was possible to estimate initial
      CO(2) concentrations as a model parameter, and therefore automatic correction for
      the CO(2) disturbances was achieved. This was important to detect low conversions
      at low buffer concentrations.

PMID- 11460254
TI  - Effects of preculture variability on clavulanic acid fermentation.
AB  - The production profile of clavulanic acid by Streptomyces clavuligerus was shown
      to be strongly dependent on inoculum activity. Two sets of fermentations (A and
      B) were investigated at industrial pilot-plant scale using complex media. Type A
      fermentations were inoculated using late exponential growth phase mycelia. Type B
      fermentations were inoculated using mycelia harvested at stationary phase.
      Productivities throughout type A fermentations were consistently higher than type
      B, reaching a maximum at about 70 h and then decaying to the same final
      productivities at 140 h of type B runs. Several scheduling alternatives, based on
      combinations of the two inocula types and different fermentation lengths, were
      compared in terms of the overall process economics (fermentation and downstream).
      An increase of ca. 22% on the overall process profit is predicted using late
      exponential growth phase inocula and a fermentation duration of only 96 h. A new
      operating strategy was thus proposed for inoculum production based on the control
      of preculture activity using off-gas analysis. This method ensures higher
      productivity and better batch-to-batch reproducibility of clavulanic acid
      fermentations than traditional methods based on constant age inocula.

PMID- 11460255
TI  - Interfacial photopolymerization of beta-cell clusters: approaches to reduce
      coating thickness using ionic and lipophilic dyes.
AB  - Microencapsulation of insulin-secreting cells is a potential therapy for Type I
      diabetes. Critical requirements for therapeutic use are the high number of beta
      cells to be implanted and a fast insulin diffusion through the encapsulating
      membrane. The use of thin, conformal coating for beta-cell encapsulation may be a
      way to reach these goals by decreasing the capsule void volume. This study
      focuses on the production of very thin membranes by interfacial
      photopolymerization of beta-cell clusters. Two types of photosensitizing dyes
      were used: Eosin Y, which stains the cell surface as well as the cytoplasm, and a
      lipophilic-derivatized eosin that specifically stains the cell membrane. The
      fraction of encapsulated clusters and membrane thickness were studied as a
      function of irradiation parameters. In the case of Eosin Y, the fraction of
      encapsulated clusters is found to depend mainly on an optimal light dose for and
      above which complete encapsulation is obtained. We found that the membrane
      thickness decreased with decreasing irradiation time, but does not depend on
      irradiation intensity. Using Eosin Y, 16 microm thick coatings were obtained,
      together with a high fraction of encapsulated clusters. The coating thickness was
      further reduced to 10 microm by using the lipophilic-derivatized eosin
      photoinitiator. Cell viability and functionality were studied following the
      encapsulation process using vital staining and measurement of insulin secretion.
      Cell viability and functionality were preserved following the encapsulation
      process with Eosin Y and for sufficiently low lipophilic dye concentration.
      Although it still requires further improvement, the method proposed here provides
      a promising route to obtain thinner coatings, down to a few microns.

PMID- 11460256
TI  - MALDI-TOF MS for quantification of substrates and products in cultivations of
      Corynebacterium glutamicum.
AB  - The application of MALDI-TOF MS for the quantification of lysine, alanine, and
      glucose is described. The method is based on using stable isotopes as internal
      standards and allows fast, sensitive, and reproducible quantification of these
      compounds. It is demonstrated for aqueous standard solutions with concentrations
      of the analytes between 10 microM and 100 mM. The mean standard deviations from
      five replicates each were 4.3% (lysine), 3.7% (alanine), and 3.2% (glucose). In
      addition, sucrose could be measured by MALDI-TOF MS, but was not quantified due
      to lack of an internal standard. The method developed can be applied to quantify
      metabolites in cultivations of C. glutamicum ATCC 21253, without processing of
      the sample except a 1:5 dilution. Excellent agreement of the data with
      conventional techniques like HPLC or enzyme assay was found.

PMID- 11460258
TI  - Selection bias in Teratology Information Service pregnancy outcome studies.
AB  - BACKGROUND: Pregnancy outcome studies conducted through Teratology Information
      Services (TIS) rely on volunteer subjects. If these subjects tend to have
      different risk profiles than the population from which they are drawn, the
      results of TIS studies may have limited generalizability. METHODS: We selected
      all subjects who enrolled in the California Teratogen Information Service (CTIS)
      pregnancy outcome study for prenatal exposure to carbamazepine or valproic acid
      between 1990 and 1997 and who received prenatal care through Kaiser Permanente of
      Southern California (n = 13). We compared these subjects to Kaiser patients
      identified through the Maternal Serum Alpha Fetoprotein Program with exposure to
      carbamazepine or valproic acid but who had not enrolled in the CTIS project. The
      controls were matched by Kaiser location and pregnancy year using a 2:1 ratio (n
      = 26). Medical records were reviewed and the prevalence of 14 pregnancy risk
      factors was compared between the two groups. RESULTS: There were no significant
      differences between the groups on any one risk factor; however, a notably higher
      proportion of women who did not enroll in the CTIS study used tobacco or had a
      positive family history of congenital anomalies. CONCLUSIONS: Although the sample
      was small, and results may not apply to other exposures in different health care
      environments, these data provide some evidence that women who enroll in TIS
      pregnancy outcome studies do not have a substantially different pregnancy risk
      profile than women who do not. Efforts to address possible selection bias should
      be incorporated in future TIS study design.

PMID- 11460259
TI  - Septo-optic dysplasia as a manifestation of valproic acid embryopathy.
AB  - BACKGROUND: The use of valproic acid during pregnancy has been associated with
      adverse fetal outcomes, including major and minor congenital malformations,
      intrauterine growth retardation (IUGR), hyperbilirubinemia, hepatotoxicity,
      transient hyperglycemia, and fetal and neonatal distress. In addition,
      intrauterine exposure to valproic acid has been associated with an increased risk
      of central nervous system abnormalities, primarily neural tube defects. Optic
      nerve hypoplasia has been reported in association with other prenatal
      anticonvulsant exposures, but the occurrence of septo-optic dysplasia as a
      manifestation of valproic acid embryopathy has not been reported previously.
      RESULTS: We report on a woman who received Depakote (valproic acid) throughout
      her pregnancy for the treatment of a seizure disorder. The patient presented with
      features typical of valproic acid embryopathy, including bitemporal narrowing,
      hypertelorism, short palpebral fissures, epicanthal folds, microphthalmia, a flat
      broad nasal bridge, small mouth, hypoplastic nails, mild clinodactyly, and
      camptodactyly. MRI showed hypoplasia of the optic chiasm and absence of the
      septum pellucidum. CONCLUSIONS: We report the first case of septo-optic dysplasia
      associated with maternal exposure to valproic acid throughout pregnancy. This
      case expands the clinical phenotype of valproate embryopathy.

PMID- 11460260
TI  - Effects of cadmium on formation of the ventral body wall in chick embryos and
      their prevention by zinc pretreatment.
AB  - BACKGROUND: Cadmium (Cd) is an established experimental teratogen whose effects
      can be reversed by pretreatment with zinc. Mesodermal development is a frequently
      reported target for Cd teratogenicity. The aim of this study was to examine the
      mechanisms of Cd induced body wall defects in chick embryos. METHODS: Chick
      embryos in shell-less culture were treated with 50 microl of cadmium acetate (8.9
      x 10(-5) M Cd(2+)) at 60-hr incubation (H.-H. stages 16-17). Controls received
      equimolar sodium acetate. Other embryos were treated with various concentrations
      of zinc acetate and then with Cd or NaAc 1 hrs later. Development was evaluated
      48 hrs later. Resin-embedded 1-microm sections were examined at earlier stages.
      RESULTS: Cd caused embryolethality (35%), ventral body wall defect with
      malpositioned lower limbs (40%), and weight reduction in survivors. After 4-hr
      treatment with Cd, breakdown of junctions between peridermal cells with rounding
      up and desquamation occurred. Shape changes were also seen in the basal layer of
      the ectoderm. At 4 hr, cell death was evident in lateral plate mesoderm, somites,
      and neuroepithelium; the lateral plate mesoderm began to grow dorsally, carrying
      the attached limb buds with it. Zn pretreatment protected against the lethal,
      teratogenic, and growth-retarding effects of Cd, as well as ectodermal changes
      and cell death. CONCLUSIONS: Cd disrupts peridermal cell adhesion and induces
      cell death in the mesoderm. This may result in abnormal growth of lateral plate
      mesoderm and in a body wall defect. Zn pretreatment prevents both the gross
      teratogenic effects and the cellular changes, most likely by competition with Cd.

PMID- 11460261
TI  - Maternal diabetes: an independent risk factor for major cardiovascular
      malformations with increased mortality of affected infants.
AB  - BACKGROUND: Intensive medical care of women with diabetes has reduced their risks
      of bearing infants with congenital anomalies. To assess the preventive potential
      of preconceptional care, the data of a population-based study of cardiovascular
      malformations (CVM) were analyzed to determine the morphogenetic specificity of
      maternal diabetes risks, the morbidity and mortality of the infants, and maternal
      characteristics that might affect these risks. METHODS: The Baltimore-Washington
      Infant Study was a case-control study (1981-1989) that included all live born
      infants with confirmed CVM; control infants were a representative sample of the
      birth cohort. A questionnaire administered in home visits recorded parental
      information on social, medical, occupational, and environmental factors. For
      these analyses of preconceptional diabetes risks, the case group excluded
      chromosomal and mendelian disorders and was divided into 3 developmental
      categories and 12 diagnostic groups. RESULTS: Preconceptional maternal diabetes
      was strongly associated with CVM of early embryonic origin (odds ratio [OR] =
      4.7, 95% confidence interval [CI] 2.8-7.9) and with cardiomyopathy (OR = 15.1,
      95% CI 5.5-41.3), but not with obstructive and shunting defects (OR = 1.4, 95% CI
      0.7-3.0). There was heterogeneity within these developmental categories: among
      laterality defects, diabetes was associated only with cardiovisceral and
      atrioventricular discordance (OR = 10.0, 95% CI 3.7-27.0); among outflow tract
      anomalies, the risk was strongly associated with normally related great arteries
      (OR = 6.6, 95% CI 3.2-13.3) but not with simple transpositions; and among
      atrioventricular septal defects, diabetes was associated with the complete but
      not with the partial forms (OR = 22.8, 95% CI 7.4-70.5). The association in early
      CVM was strongest among infants with multisystem, predominantly VACTERL,
      anomalies. All-cause mortality of infants with CVM was 39% among those with
      diabetic mothers and 17.8% in those with nondiabetic mothers. Deceased infants of
      diabetic mothers were also more likely to have extracardiac anomalies (P =
      0.041), to be born prematurely (P = 0.007), and to have low birth weight (P =
      0.011). Multivariate analyses of maternal factors revealed no significant
      confounders of the diabetes associations. CONCLUSIONS: The evidence of diabetes
      induced major cardiac defects is of urgent clinical significance. The
      effectiveness of early preconceptional care in the prevention of congenital
      anomalies has been demonstrated repeatedly.

PMID- 11460262
TI  - Brain, eye, and face defects as a result of ectopic localization of Sonic
      hedgehog protein in the developing rostral neural tube.
AB  - BACKGROUND: Normal development of the face, eyes, and brain requires the
      coordinated expression of many genes. One gene that has been implicated in the
      development of each of these structures encodes the secreted protein, Sonic
      hedgehog (Shh). During central nervous system development, Shh is required for
      ventral specification along the entire neural axis. To further explore the role
      of Shh in chick brain and craniofacial development, we overexpressed Shh in the
      developing rostral neural tube METHODS: In order to determine if Shh is
      sufficient to ventralize the forebrain, we localized ectopically recombinant Shh
      protein to the rostral neural tube of chick embryos. The resulting embryos were
      evaluated morphologically and by assaying gene expression. RESULTS: Disruption in
      normal gene expression patterns was observed with a reduction or loss in
      expression of genes normally expressed in the dorsal forebrain (wnt-3a, wnt-4,
      and Pax-6) and expansion of ventrally expressed genes dorsally (HNF-3beta, Ptc).
      In addition to the genetic alterations observed in the neural tube, a
      craniofacial phenotype characterized by a reduction in many cranial neural crest
      derived structures was observed. The eyes of Shh-treated embryos were also
      malformed. They were small with expansion of the retinal pigmented epithelium,
      enlarged optic stalks, and a reduction of neural retina. DISCUSSION: The ectopic
      localization of recombinant Shh protein in the rostral neural tube resulted in
      severe craniofacial anomalies and alterations of gene expression predicted by
      other studies. The system employed appears to be a model for studying the
      embryogenesis of malformations that involve the brain, eyes, and face.

PMID- 11460263
TI  - Inhibitors of choline uptake and metabolism cause developmental abnormalities in
      neurulating mouse embryos.
AB  - BACKGROUND: Choline is an essential nutrient in methylation, acetylcholine and
      phospholipid biosynthesis, and in cell signaling. The demand by an embryo or
      fetus for choline may place a pregnant woman and, subsequently, the developing
      conceptus at risk for choline deficiency. METHODS: To determine whether a
      disruption in choline uptake and metabolism results in developmental
      abnormalities, early somite staged mouse embryos were exposed in vitro to either
      an inhibitor of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), or
      an inhibitor of phosphatidylcholine synthesis, 1-O-octadecyl-2-O-methyl-rac
      glycero-3-phosphocholine (ET-18-OCH(3)). Cell death following inhibitor exposure
      was investigated with LysoTracker Red and histology. RESULTS: Embryos exposed to
      250-750 microM DMAE for 26 hr developed craniofacial hypoplasia and open neural
      tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed
      to 125-275 microM ET-18-OCH(3) exhibited similar defects or expansion of the
      brain vesicles. ET-18-OCH(3)-affected embryos also had a distended neural tube at
      the posterior neuropore. Embryonic growth was reduced in embryos treated with
      either DMAE (375, 500, and 750 microM) or ET-18-OCH(3) (200 and 275 microM).
      Whole mount staining with LysoTracker Red and histological sections showed
      increased areas of cell death in embryos treated with 275 microM ET-18-OCH(3) for
      6 hr, but there was no evidence of cell death in DMAE-exposed embryos.
      CONCLUSIONS: Inhibition of choline uptake and metabolism during neurulation
      results in growth retardation and developmental defects that affect the neural
      tube and face.

PMID- 11460264
TI  - Rapid effects of triiodothyronine on immediate-early gene expression in Schwann
      cells.
AB  - In the peripheral nervous system, triiodothyronine (T3) plays an important role
      in the development and regeneration of nerve fibers and in myelin formation.
      However, the target genes of T3 in peripheral nerves remain to be identified. We
      investigated whether T3 activated genes of transcription factors in Schwann
      cells. Expression of egr-1 (krox-24), egr-2 (krox-20), egr-3, c-jun, junB, c-fos,
      fosB, fra-1, fra-2, and CREB genes was analyzed by reverse transcription
      polymerase chain reaction (RT-PCR) in Schwann cells isolated from neonatal rat
      sciatic nerves and in the cell lines MSC-80 (mouse Schwann cells), NIH-3T3 (mouse
      fibroblasts), and CHO (Chinese hamster ovary cells). Some of these transcription
      factors have been shown to be involved in Schwann cell differentiation. T3
      triggered a rapid (15-30 min), transient (1-2-h) and strong (6- to 15-fold)
      stimulation of Egr-1, Egr-2, Egr-3, Jun B, c-Fos, and Fos B mRNA expression in
      Schwann cells. In contrast, expression of c-Jun, Fra-1, Fra-2, and CREB mRNA was
      not affected by T3. The stimulatory effects of T3 could be abolished by adding
      actinomycin D. T3 triggered the same pattern of gene stimulation in the mouse
      Schwann cell line MSC80, but not in the NIH-3T3 and CHO cell lines. Serum
      activated all the genes that responded to T3 and in addition fra-1 and fra-2, but
      not c-jun and CREB. Immunoblotting showed that the increase in Egr-1 and c-Fos
      mRNA levels was accompanied by an increase in the corresponding proteins. In
      addition, shifts of the protein bands indicated a posttranslational modification
      of the two proteins. These effects of T3 are likely to be mediated by the
      intracellular T3 receptor, as the D-isomer RT3 and T0, which do not bind to T3
      receptors, proved ineffective. The present data suggested that T3 may regulate
      Schwann cell functions and differentiation by transiently activating the
      expression of specific transcription factors.

PMID- 11460265
TI  - The triakontatetraneuropeptide TTN increases [CA2+]i in rat astrocytes through
      activation of peripheral-type benzodiazepine receptors.
AB  - Astrocytes synthesize a series of regulatory peptides called endozepines, which
      act as endogenous ligands of benzodiazepine receptors. We have recently shown
      that one of these endozepines, the triakontatetraneuropeptide TTN, stimulates DNA
      synthesis in astroglial cells. The purpose of the present study was to determine
      the mechanism of action of TTN on cultured rat astrocytes. Binding of the
      peripheral-type benzodiazepine receptor ligand [3H]Ro5-4864 to intact astrocytes
      was displaced by TTN, whereas its C-terminal fragment (TTN[17-34], the
      octadecaneuropeptide ODN) did not compete for [3H]Ro5-4864 binding.
      Microfluorimetric measurement of cytosolic calcium concentrations ([Ca2+]i) with
      the fluorescent probe indo-1 showed that TTN (10(-10) to 10(-6) M) provokes a
      concentration-dependent increase in [Ca2+]i in cultured astrocytes. Simultaneous
      administration of TTN (10(-8) M) and Ro5-4864 (10(-5) M) induced an increase in
      [Ca2+]i similar to that obtained with Ro5-4864 alone. In contrast, the effects of
      TTN (10(-8) M) and ODN (10(-8) M) on [Ca2+]i were strictly additive. Chelation of
      extracellular Ca2+ by EGTA (6 mM) or blockage of Ca2+ channels with Ni2+ (2 mM)
      abrogated the stimulatory effect of TTN. The calcium influx evoked by TTN (10(-7)
      M) or by Ro5-4864 (10(-5) M) was not affected by the N- and T-type calcium
      channel blockers omega-conotoxin (10(-6) M) and mibefradil (10(-6) M), but was
      significantly reduced by the L-type calcium channel blocker nifedipine (10(-7)
      M). Patch-clamp studies showed that, at negative potentials, TTN (10(-7) M)
      induced a sustained depolarization. Reduction of the chloride concentration in
      the extracellular solution shifted the reversal potential from 0 mV to a positive
      potential. These data show that TTN, acting through peripheral-type
      benzodiazepine receptors, provokes chloride efflux, which in turn induces calcium
      influx via L-type calcium channels in rat astrocytes.

PMID- 11460266
TI  - Schwann cell myelination occurred without basal lamina formation in laminin
      alpha2 chain-null mutant (dy3K/dy3K) mice.
AB  - The laminin alpha2 chain is a major component of basal lamina in both skeletal
      muscle and the peripheral nervous system. Laminin alpha2 chain deficiency causes
      merosin-deficient congenital muscular dystrophy, which affects not only skeletal
      muscles, but also the peripheral and central nervous systems. It has been
      reported that the formation of basal lamina is required for myelination in the
      peripheral nervous system. In fact, the spinal root of dystrophic mice (dy/dy
      mice), whose laminin alpha2 chain expression is greatly reduced, shows lack of
      basal lamina and clusters of naked axons. To investigate the role of laminin
      alpha2 chain and basal lamina in vivo, we examined the peripheral nervous system
      of dy3K/dy3K mice, which are null mutants of laminin alpha2 chain. The results
      indicate the presence of myelination although Schwann cells lacked basal lamina
      in the spinal roots of dy3K/dy3K mice, suggesting that basal lamina is not an
      absolute requirement for myelination in vivo. Immunohistochemically, the
      expression of laminin alpha4 chain was increased and laminin alpha5 chain was
      preserved in the endoneurium of the spinal root. Laminin alpha4 and alpha5 chains
      may play the critical role in myelination instead of laminin alpha2 chain in
      dy3K/dy3K mice. In addition, the motor conduction velocity of the sciatic nerve
      was significantly reduced compared with that of wild-type littermate. This
      reduction in conduction velocity may be due to small axon diameter, thin myelin
      sheath and the patchy disruption of the basal lamina of the nodes of Ranvier in
      dy3K/dy3K mice.

PMID- 11460267
TI  - Activation of mitogen-activated protein kinase by muscarinic receptors in
      astroglial cells: role in DNA synthesis and effect of ethanol.
AB  - Mitogen-activated protein kinase (MAPK) can be phosphorylated by mitogens binding
      to G-protein-coupled receptors and is considered a major pathway involved in cell
      proliferation. In this study, we report on the activation of MAPK by muscarinic
      acetylcholine receptors in astroglial cells, namely the 1321N1 human astrocytoma
      cell line, primary rat cortical astrocytes, and fetal human astrocytes. Carbachol
      caused a rapid and transient phorphorylation of MAPK (ERK1/2) in all cell types,
      with an increase in MAPK activity, without changing the levels of MAPK proteins.
      Human astrocytoma cells were used to characterize the effect of carbachol on
      MAPK. Experiments with M2- and M3-receptor subtype-selective antagonists, and
      with pertussis toxin, indicated that the M3 subtype is responsible for activating
      MAPK in glial cells. Pretreatment of cells with the protein kinase C (PKC)
      inhibitor bisindolylmaleimide I, or downregulation of PKC by 24-h treatment with
      the phorbol ester TPA inhibited carbachol-induced MAPK activation. Additional
      experiments with PKC alpha- or PKC epsilon-specific compounds indicated that the
      epsilon isozyme of PKC is primarily involved in MAPK activation by carbachol.
      Chelation of calcium also inhibited MAPK activation by carbachol. Two MEK (MAPK
      kinase) inhibitors inhibited carbachol-induced DNA synthesis but only at
      concentrations that exceeded those sufficient to block carbachol-induced MAPK
      activation. Ethanol (< or =200 mM) had no effect on MAPK when present alone and
      did not affect carbachol-induced MAPK activation under various experimental
      conditions, although it inhibits carbachol-induced DNA synthesis at low
      concentrations (10-100 mM). These results suggest that activation of MAPK by
      carbachol may be necessary but not sufficient for its mitogenic effect in
      astroglial cells, and that does not represent a target for ethanol-induced
      inhibition of DNA synthesis elicited by muscarinic receptors.

PMID- 11460268
TI  - Ischemia-induced apoptosis in primary cultures of astrocytes.
AB  - Astrocytes participate in a wide variety of important physiological processes and
      pathological insults, including ischemia. Information on the mechanism of
      astroglial injury and death during ischemic insult, however, is scarce. In this
      study, we investigated the mode of astrocytic cell death using an in vitro
      ischemic model. Cultured astrocytes exhibited several distinct morphological and
      biochemical features of apoptosis under ischemia. At 4 h of ischemia, Annexin V
      staining demonstrated an early commitment of some astrocytes to apoptosis.
      Condensed nuclei became visible from 4 h and the number increased with ischemic
      incubation time. Electron microscopy showed compacted and segregated chromatin
      along the edges of nuclear membranes. The number of TUNEL-positive nuclei and the
      degree of DNA laddering increased with ischemic incubation. Caspase-3, but not
      caspase-1, activity was increased in ischemia-injured astrocytes. Swollen
      mitochondria and vacuoles found in some cells with chromatin condensation
      indicated that these apoptotic-like cells might die of necrosis. The results
      imply that astrocytes are capable of undergoing apoptosis without the presence of
      other cell types, such as neurons. Ischemia can induce apoptosis in astrocytes
      contributing to the pathogenesis of ischemic injury in the CNS.

PMID- 11460269
TI  - Angiotensin receptor-like immunoreactivity in adult brain white matter astrocytes
      and oligodendrocytes.
AB  - Most of the physiological effects of brain angiotensins are currently believed to
      be mediated by angiotensin receptors located principally on neurons. However,
      numerous studies in vitro have demonstrated the presence of functional
      angiotensin receptors on brain astrocytes, raising the possibility that glial
      cells may also participate in mediating the effects of the central renin
      angiotensin system. Nevertheless, it is uncertain whether these cells in situ
      express angiotensin receptors, raising questions about the physiological
      significance of results observed in cell cultures. We have examined the
      distribution of angiotensin receptor-like immunoreactivity in glial cells in
      white matter tracts in the adult CNS, using a panel of antisera to the AT1 and
      AT2 angiotensin receptors. Antiserum preadsorption and/or Western blot
      demonstrated the specificity of the antisera in brain tissue. In
      immunohistochemical experiments, the AT1 antisera selectively labeled AT1
      expressing neurons in the piriform cortex, whereas the AT2 antiserum stained
      cells in the trigeminal motor nucleus, these being nuclei known to express AT1
      and AT2 receptors, respectively. Using double-label immunohistochemistry, we
      observed AT1- and AT2-immunoreactive astrocytes and oligodendrocytes in white
      matter tracts, which include the rat cerebellar white matter, periventricular
      white matter, and optic nerve, in addition to the bovine corpus callosum and
      human subcortical white matter. In contrast, astrocytes in the gray matter region
      of the cerebral cortex were not found to be angiotensin receptor-like
      immunoreactive. These results demonstrate the presence of AT1 and/or AT2
      angiotensin receptor-like immunoreactivity in brain white matter macroglial cells
      in situ and support the idea that glial cells may play a more important role in
      the central renin-angiotensin system than previously thought.

PMID- 11460270
TI  - Neu differentiation factor regulates tau protein and mRNA in cultured neonatal
      oligodendrocytes.
AB  - Axonal signals activate myelinogenesis via regulation of the extent to which
      oligodendrocyte (OLG) processes wrap around the axon. The cytoskeleton in OLG
      processes is actively involved in myelination and is a putative target for axonal
      regulation of myelination. The axon-associated neuregulins may regulate the
      cytoskeleton extensions in OLG processes. Here, we report that the neuregulin neu
      differentiation factor (NDF) increases the expression of tau mRNA and tau protein
      in OLGs. Treatment of neonatal OLGs with alpha-NDF or beta-NDF resulted in
      dramatic increases in the length of OLG processes, which appeared either as
      singular unbranched extensions or as a network of extensively branched processes.
      By immunoblot analysis with tau-1 mAb, which recognizes the dephosphorylated form
      of the tau proteins, neonatal OLGs treated with alpha-NDF or beta-NDF, had an
      increase in tau protein levels. The increase of tau levels in beta-NDF-treated
      cells is much greater than the twofold increase present in alpha-NDF-treated
      cells. By immunoblot analysis with the phosphorylation-insensitive tau-5 mAb,
      beta-NDF-treated cells had a twofold increase in tau. Immunoblot analysis suggest
      that alpha-NDF and beta-NDF promote a twofold increase in the tau protein levels
      in OLG, with the beta-factor also promoting a tau dephosphorylation. Using
      promoters spanning the amino-terminal region of tau, we found that OLGs treated
      with alpha-NDF or beta-NDF contained approximately twofold more tau mRNA than
      untreated cells. However, there was no qualitative difference between control and
      NDF-treated cells in the pattern of tau mRNA isoforms expressed. A model is
      proposed in which the axonal NDF-induced regulation of tau expression in OLGs may
      be part of the mechanism by which the axon regulates myelination.

PMID- 11460273
TI  - 50th International Congress of the European Society for Cardiovascular Surgery.
      June 20-23, 2001. Budapest, Hungary. Abstracts.

PMID- 11460271
TI  - Endogenous opioids and oligodendroglial function: possible autocrine/paracrine
      effects on cell survival and development.
AB  - Previous work has shown that oligodendrocytes (OLs) express both micro- and kappa
      opioid receptors. In developing OLs, micro receptor activation increases OL
      proliferation, while the kappa-antagonist nor-binaltorphimine (NorBNI) affects OL
      differentiation. Because exogenous opioids were not present in our defined
      culture medium, we hypothesized that NorBNI blocked endogenous opioids produced
      by the OLs themselves. To test this, intact and partially processed proenkephalin
      and prodynorphin-derived peptides were assessed in OLs using immunocytochemistry
      or Western blot analysis, or both. Immature OLs possessed large amounts of intact
      and partially processed proenkephalin precursors, as well as posttranslational
      products of prodynorphin including dynorphin A (1-17). With maturation, however,
      intact or partially processed proenkephalin was expressed by only about 50% of
      OLs, while dynorphin A (1-17) was undetectable. To assess the function of OL
      derived opioids, the effect of kappa-agonists/antagonists on OL differentiation
      and death was explored. kappa-Agonists alone had no effect. In contrast, NorBNI
      significantly increased OL death. Additive OL losses were evident when NorBNI was
      paired with toxic levels of glutamate, suggesting that kappa-receptor blockade
      alone is sufficient to induce OL death. Thus, the results indicate that OLs
      express proenkephalin and prodynorphin peptides in a developmentally regulated
      manner, and further suggest that opioids produced by OLs modulate OL maturation
      and survival through local (i.e., autocrine and/or paracrine) mechanisms.

PMID- 11460274
TI  - Comparative anti-caries effects of tablet and liquid fluorides in cleft children.
AB  - Children with cleft lip and/or palate are at a higher risk for developing caries
      of the primary incisors compared with non-cleft children. To determine whether
      fluoride in tablet or liquid form would be more efficacious with children with
      cleft lip and/or palate, a two-year clinical investigation was conducted to test
      the anti-caries effects. One-hundred and fifteen cleft children (59 boys and 56
      girls) between 22 and 26 months old were randomly selected into control, tablet
      and liquid fluoride groups. The amount of administered fluoride was 0.25 mg F
      daily in non-fluoridated Taiwan. Dental examinations were conducted using mirrors
      and #23 explorers. Caries were assessed using the DMF index in the baseline,
      first year and second year. The results showed that children in the tablet and
      liquid groups had a significantly lower DMFT increment than in the control group
      (p < 0.05). In the DMFS index, children in the liquid group showed a
      significantly lower caries increment than in the control group (p < 0.01), and
      children in the tablet group presented a borderline, but non-significant
      statistical difference when compared with the control group (p = 0.065). No
      significant statistical difference was found in either DMFT or DMFS between
      tablet and liquid fluoride administrations (p = 0.521 and p = 0.383,
      respectively). It is concluded that dietary fluoride supplements in liquid form
      show efficacy in reducing early childhood caries in the cleft children. Liquid
      fluoride showed slightly better numerical anti-caries effect than tablet
      fluoride, which is possibly due to its ease of administration with small
      children.

PMID- 11460275
TI  - Plaque regrowth effects of a triclosan/pyrophosphate dentifrice in a 4-day non
      brushing model.
AB  - Triclosan is a lipophilic antimicrobial agent which, when present in an aqueous
      dentifrice vehicle, is complexed by or in close contact with polymers and surface
      active molecules, emulsifying agents, flavoring oils and other hydrophobic
      ingredients. Because of this, dentifrice products containing triclosan may not
      have triclosan in a bioavailable state and, hence, the products themselves can
      not be assumed to possess antimicrobial activity. In order to determine the
      antimicrobial effects on dental plaque of a triclosan/pyrophosphate dentifrice
      relative to a negative control (without triclosan or pyrophosphate), a crossover
      4-day non-brushing study was conducted. Thirty-four subjects were enrolled in
      this randomized two-period, double-blind crossover investigation with thirty
      three subjects completing all aspects. Following a baseline plaque examination
      and complete plaque removal at the start of the first 4-day treatment period,
      subjects initiated a twice-daily supervised dosing regimen, during which they
      rinsed with their first assigned dentifrice in slurry form while refraining from
      tooth-brushing and all other oral hygiene procedures. Evaluations to quantify
      test product effects on plaque were conducted on Day 5. After a week-long interim
      washout period, subjects repeated the twice daily rinsing regimen over Days 1-4
      of Treatment Period 2 with their second assigned product, again with examinations
      on Day 5. Analysis of data demonstrated subjects had significantly (p = 0.0296)
      less plaque when rinsing with the triclosan/pyrophosphate dentifrice slurry as
      compared to the negative control dentifrice slurry; the relative treatment
      difference as determined by the primary examiner was 12.7%. A trainee examiner
      observed a 16.0% reduction on a subset of subjects (p = 0.0139). This efficacy
      result compares favorably with results from other studies of triclosan-containing
      products. The examinations for oral safety demonstrated no meaningful clinical
      differences between the triclosan/pyrophosphate dentifrice and control
      dentifrice.

PMID- 11460276
TI  - Fluoride release from a toothbrush.
AB  - The purpose of the present study was to evaluate the fluoride concentration in
      unstimulated saliva after using a toothbrush with 9,048 ppm fluoride as sodium
      fluoride incorporated in the bristles. A toothpaste with 1,500 ppm fluoride
      served as the positive control. Twelve volunteers took part in the single-blind
      crossover study. In a pre-test phase of 14 days, the subjects refrained from
      eating fluoride-rich foods and did not use any fluoride-containing products for
      oral hygiene measures. This was followed by a test period of four weeks. At day
      one and after 14 and 28 days, unstimulated saliva was collected and analyzed for
      its fluoride content. Saliva was collected immediately after toothbrushing and
      after 15, 30, 60, 90, 120 150, and 180 minutes. On day one, the fluoride
      toothbrush released significant amounts of fluoride immediately after the
      brushing, and after 15 and 30 minutes (p < 0.01). After 14 days of use, this
      could be found immediately after brushing and after 15 minutes (p < 0.01 or p <
      0.05, respectively). After 28 days, a significant fluoride release was only found
      immediately after brushing (p < 0.05). On all days, compared to the positive
      control, the fluoride release from the fluoride toothbrush was generally lower
      immediately after brushing and after 15 minutes (p < 0.001, p < 0.01 or p < 0.05,
      respectively). It may be concluded that a toothbrush with incorporated sodium
      fluoride could act as a fluoride-releasing. device.

PMID- 11460277
TI  - A rapid method for evaluating microbicidal activity of dentifrice formulations
      against salivary bacteria ex vivo.
AB  - A new rapid ex vivo method was developed for evaluating the short-term
      bactericidal activity of dentifrices against salivary microorganisms. Dentifrice
      aliquots of 0.25 or 1.0 g were rapidly dispersed into 3.5 mL of freshly pooled
      human saliva, and 1.0 mL aliquots of the dentifrice-saliva suspension were
      collected after 30 or 60 seconds of exposure, diluted in neutralizing broth and
      plated on non-selective agar media for enumeration of surviving total cultivable
      microflora. Eight experimental dentifrices containing increasing amounts (0 to
      2.6%) of a fixed ratio of essential oils (thymol, menthol, methyl salicylate and
      eucalyptol) were dispersed in saliva at a 0.25:3.5 (w/v) dentifrice:saliva ratio.
      Recoverable CFUs/mL at 30 sec. were reduced in a dose-responsive manner from >
      10(6) to < 10(4). Additional tests using both 0.25 and 1.0 g amounts of
      dentifrice prototypes containing 2.1% of the essential oil mixture showed that
      the experimental dentifrices exhibited highly significant (approximately 2.5 log)
      reductions in viable recoverable microorganisms relative to essential oil-free
      placebos after both 30- and 60-second exposures. When compared to in vitro models
      previously used to evaluate the antimicrobial activity of dentifrices, this
      method provides a rapid, reproducible, more biologically representative means of
      screening dentifrice formulations for microbicidal activity using dilutions and
      exposure times approximating those achieved during toothbrushing. However, since
      other factors may influence microbicidal activity of dentifrice formulations in
      vivo, conclusions drawn using this model require clinical confirmation.

PMID- 11460278
TI  - In vivo antimicrobial activity of an essential oil-containing mouthrinse on
      interproximal plaque bacteria.
AB  - This study determined the in vivo interproximal bactericidal efficacy of an
      essential oil-containing antiseptic mouthrinse (Listerine Antiseptic) following
      toothbrushing. Thirty-four generally healthy adults, aged 23-64 years, completed
      this evaluator-blind, randomized, controlled, crossover designed study. Subjects
      rinsed for 30 seconds with 20 ml of either the essential oil rinse or a negative
      control rinse. Five minutes later, interproximal plaque was collected using paper
      points, and recoverable bacterial counts were quantified using both end point
      dilution and spectrophotometric methods. The results from the end point dilution
      demonstrated a statistically significant (p < 0.001) 43.8% reduction in
      recoverable plaque bacteria from interproximal spaces following rinsing with the
      essential oil mouthrinse. This study suggests that the clinical effectiveness of
      the essential oil mouthrinse against plaque and gingivitis may be attributable to
      the rapid kill and plaque permeabilizing properties of the formulation.

PMID- 11460279
TI  - Effect of denture adhesive on retention of the mandibular and maxillary dentures
      during function.
AB  - The purpose of this study was to determine the effect of denture adhesive on
      retention of mandibular and maxillary dentures over a four-hour period. Denture
      movements were measured using an alternating magnetic field tracking device that
      determines the position of magnetic receiver coils relative to a transmitter coil
      positioned over the head. Ten adults with complete maxillary dentures and
      complete mandibular implant overdentures were enrolled in the study. Specially
      fabricated mandibular dentures contained a relief area that exposed the implant
      post which no longer anchored the denture, but now served as an attachment point
      for a receiver coil that measured mandibular movement. The denture coil was
      attached lateral to the post coil on a shelf cut into the denture. Mandibular
      denture movements were recorded as the difference between the mandible movement
      signal and the mandible + mandibular denture signals. Measurements of denture
      movements were made at baseline (no adhesive) and at 0, 2, 4 hours post-adhesive
      application with Fixodent cream for standardized chewing and biting. The
      MoveTrack signals were recorded on a digital data cassette recorder for
      subsequent computer analysis. The results of the measurements were analyzed using
      paired sample t-tests. Specifically, the following comparisons of movement means
      were made: mandibular vs. maxillary, baseline vs. post-baseline and successive
      changes (e.g., baseline vs. hour 0, hour 0 vs. hour 2, etc.). Results of these
      analyses showed that: 1) mandibular denture movements under both adhesive and non
      adhesive conditions were significantly greater than maxillary denture movements;
      2) the adhesive significantly reduced movement of the maxillary and mandibular
      dentures during both chewing and biting; and 3) the improvement occurred
      immediately post-application of the adhesive and was maintained for the four
      hours of follow-up.

PMID- 11460280
TI  - Clinical comparison of plaque removal and gingival bleeding reduction by two
      different brush heads on a sonic toothbrush.
AB  - Previous clinical studies have demonstrated the efficacy of a sonic toothbrush
      (Sonicare) in plaque removal and reduction of gingival inflammation. Currently,
      several different brush heads are available for this sonic toothbrush. The
      purpose of this clinical study was to compare two different brush heads (nine row
      and eight row) with respect to their ability to remove dental plaque and reduce
      gingival bleeding. One-hundred twenty-one young adults, in good general and
      periodontal health, volunteered as subjects in this five-week, single-blind,
      crossover study. All subjects used one brush for a two-week period, brushing
      twice daily for two minutes. Subjects used a manual toothbrush during a one-week
      washout period, and then used the other head for two weeks. At the beginning and
      end of each two-week trial period, subjects were scored for plaque and bleeding
      by means of the Turesky modification of the Quigley-Hein Plaque Index and the
      Mombelli et al. modification of the Sulcus Bleeding Index of Muhlemann and Son.
      Findings of reductions were limited to "before vs. after" assessments. The nine
      row brush demonstrated a significant reduction (p < 0.05) in plaque removal on
      the smooth surfaces (p = 0.02) as well as significant reductions in bleeding at
      interproximal (p = 0.04) and posterior sites (p = 0.031). Overall, both brushes
      appeared to be effective in reducing dental plaque and bleeding. A questionnaire
      administered to all subjects at the end of the five-week study revealed a
      preference for the smaller of the brush heads.

PMID- 11460281
TI  - Comparison of treatment response patterns following scaling and root planing in
      smokers and non-smokers with untreated adult periodontitis.
AB  - The present study was conducted to compare short-term treatment response patterns
      following scaling and root planing in smoking and non-smoking Chinese patients
      with untreated adult periodontitis. Thirteen smokers and twelve periodontally
      matched non-smokers with untreated advanced adult periodontitis were evaluated
      prior to and at one, three, and six months after scaling and root planing.
      Probing depths (PD), probing attachment level (PAL) and gingival height (GH) were
      assessed at clinically healthy, gingivitis and periodontitis sites. PD and PAL
      were measured using electronic Florida pocket and disk probes, respectively. Non
      smokers consistently showed significant gingival shrinkage in gingivitis sites,
      whereas smokers had no significant change in GH. In periodontitis sites, both
      groups exhibited significant decreases in PD (p < 0.001) at one month, and a
      greater reduction of PD was found in non-smokers than in smokers (p < 0.05), the
      difference being most notable at three months (2.4 +/- 0.2 mm vs. 1.1 +/- 0.3 mm,
      p < 0.001). Non-smokers showed a consistent gain of attachment in periodontitis
      sites from 0.5 +/- 0.2 mm at one month (p < 0.05) to 1.2 +/- 0.3 mm at six months
      (p < 0.001), whereas no significant gain of attachment was found in smokers until
      six months (0.5 +/- 0.2 mm; p < 0.05). Overall, the reduction of PD positively
      correlated with baseline PD in both smokers (p < 0.01) and non-smokers (p <
      0.001), but when only the sites with an initial PD > or = 5 mm were considered,
      such a significant correlation was found only in non-smokers (p < 0.05). A
      positive correlation was also found between the change in PAL and baseline PD
      solely in non-smokers (p < 0.05). This study indicates that smokers have
      different treatment response patterns and healing dynamics compared to non
      smokers following scaling and root planing, suggesting that for smoking patients
      a more intensive treatment regimen is needed for a better treatment outcome and
      reduced risk for further periodontal disease progression.

PMID- 11460282
TI  - Effect of chlorhexidine varnish on bacterial levels in plaque and saliva during
      orthodontic treatment.
AB  - The plaque-retentive effects of fixed orthodontic appliances may induce a rapid
      increase in the amount of plaque. The aim of the present study was to conduct a
      longitudinal clinical investigation on the antibacterial effect of chlorhexidine
      containing Cervitec varnish during orthodontic treatment. Twenty-four subjects (9
      male, 15 female), aged 16.5 +/- 2.5 years, participated in the study. At
      baseline, the subjects' DMF-S scores, stimulated salivary flow rates (ml/min) and
      levels of salivary Streptococcus mutans (SM) and lactobacilli (LB) were
      determined using Dentocult SM strip and Dentocult LB methods. After placing the
      orthodontic appliances, the subjects were treated with Cervitec or a placebo
      varnish around the bands and brackets. The chlorhexidine varnish was applied
      randomly in the first or second quadrant, and placebo varnish in the opposite
      quadrant, according to the split-mouth technique. The varnish application was
      repeated every 3 months to the same sites. Follow-up samples of saliva and plaque
      from around brackets and bands were collected at 1, 3, 6, 9 and 12 months. Plaque
      SM and salivary SM, as well as LB counts were determined as at baseline. The
      results showed that a significantly higher proportion of plaque samples belonged
      to the low-risk category (SM count10(5) CFU/ml) on the test side than on the
      placebo side. Distribution of salivary samples between the low-risk and high-risk
      categories (based on SM and LB counts) did not change significantly until the end
      of the follow-up period. The number of new carious lesions after debonding the
      fixed orthodontic appliance was significantly lower (p < 0.05) in the Cervitec
      treated quadrant compared to the placebo varnish-treated quadrant. The results
      show that the chlorhexidine-containing varnish effectively reduced the number of
      SM in dental plaque around fixed orthodontic appliances.

PMID- 11460283
TI  - Bonding systems used for sealing: evaluation of microleakage.
AB  - To evaluate multi-use bonding systems as the sole material for sealing pits and
      fissures, this study compared the performance of three adhesives (OptiBond, All
      Bond 2 and Scotchbond MP Plus) with respect to microleakage. Each material was
      applied to 12 teeth with dry-etched surfaces, and to 12 teeth with contaminated
      etched surfaces (1 microliter of human plasma). Each group of 12 sealed teeth was
      divided into three subgroups, and each of these was subjected either to thermal
      cycling (4,000 cycles at 5-55 degrees C), to thermal and load cycling (4,000 plus
      300,000 cycles) or to no cycling. The teeth were placed in a 50% AgNO3 solution,
      rinsed, immersed in a developing solution and exposed to a fluorescent light.
      Subsequently, each of the 72 crowns was sectioned at three different positions,
      generating 432 cross-sections. The severity of dye penetration on each cross
      section was evaluated by two methods. An ANOVA was used to assess the main
      effects of the three factors (product, surface condition and cycling), as well as
      for their interactions on the severity of microleakage. The results obtained
      under both evaluation methods demonstrated that OptiBond had the best performance
      under either dry or contaminated surfaces, while All-Bond 2 and Scotchbond MP
      Plus performed similarly, with greater microleakage intensity on contaminated
      etched enamel compared to OptiBond.

PMID- 11460284
TI  - A comparative pilot study of the effects of a dentifrice containing green tea
      bioflavonoids, sanguinarine or triclosan on oral bacterial biofilm formation.
AB  - The aim of the present study was to evaluate the effect of a green tea
      bioflavonoid/zinc ascorbate-containing dentifrice (Natural Antioxidant
      Toothpaste) on bacterial plaque biofilm accumulation. Plaque biofilms were formed
      and observed on saliva-conditioned synthetic hydroxyapatite disks (HA) over 4
      days. Two test treatments were performed daily over a 4-day experimental period
      for a total of 8 treatments. Four test dentifrices were evaluated: a 0.1%
      bioflavonoid/0.2% zinc ascorbate; a non-active control test dentifrice; a 0.075%
      sanguinarine/2.0% zinc chloride dentifrice; and a 0.3% triclosan dentifrice. The
      repeated treatment of the HA with the green tea bioflavonoid/zinc ascorbate, the
      sanguinarine/zinc chloride, or the triclosan dentifrice resulted in significant
      reductions in total viable plaque biomass when compared to a non-active placebo
      control dentifrice.

PMID- 11460285
TI  - Laboratory interproximal access efficacy of two toothbrushes with cross-angulated
      bristling.
AB  - Interproximal access efficacy (IAE) has been evaluated in a laboratory method
      using pressure-sensitive paper placed around simulated anterior and posterior
      teeth, using horizontal or vertical brushing motions. The two toothbrushes
      evaluated in this study were the Oral-B Cross Action Medium 40 and the Dr. Best X
      Activ Mittel. Twenty-four tests on each toothbrush design were conducted, and
      results were statistically analyzed using ANOVA. In all of the individual
      evaluations, using either vertical or horizontal brushing motions on either
      anterior or posterior simulated teeth, the Dr. Best X-Activ Mittel toothbrush was
      significantly (p < 0.001) more effective than the Oral-B Cross Action Medium 40
      in achieving IAE. When individual IAE data from the vertical, horizontal,
      anterior and posterior assessments were combined to assess overall IAE, the Dr.
      Best X-Activ Mittel toothbrush had a significantly (p < 0.001) higher mean value
      than the Oral-B Cross Action Medium 40 mean value.

PMID- 11460286
TI  - Can Glass ionomer sealants be cost-effective?
AB  - Glass ionomer (GI), applied as a pit and fissure sealant, has been shown to be a
      promising method for caries prevention. It has also been suggested that when GI
      is used as a sealant material, it can prevent caries, even if partly or totally
      lost. As there is no need for resealing GI, it may be more cost-effective when
      compared to a resin-based (RB) sealant. This study evaluated the factors
      influencing the time needed to apply a sealant as a factor in determining the
      possible costs of the effectiveness of RB compared to GI sealants. To study this,
      children born between 1980 and 1983, who had their appropriate second molars
      sealed between 1993 and 1997, were assessed. The study was then based on a random
      sub-sample of this group, comprising 140 teeth: 86 sealed with RB (Delton) and 54
      with GI (Fuji III). For a hygienist working alone, the whole procedure of
      applying a sealant, beginning with the cleaning of the tooth and ending with the
      finished sealant, took, on average, 344 (+/- 59) seconds with RB, and 599 seconds
      (+/- 89) with GI. This difference in time was found to be statistically
      significant at p < 0.01. No statistically significant difference existed in the
      mean time required to apply a sealant between the left (410 +/- 140 seconds) and
      the right (448 +/- 149 seconds) sides; however, the mandibular teeth required
      longer for application of the sealant than did the maxillary teeth (447 +/- 161
      seconds vs. 408 +/- 125 seconds, respectively; p < 0.01). It was also found that
      a dentist, working with chairside assistance, took 20% less time to apply either
      sealant material than did the hygienist working alone. It was concluded that GI
      sealants, whether resealed or not, cannot be as cost-effective as RB sealants,
      when the expense of placement in time (and thus costs) is used as the basis of
      efficacy.

PMID- 11460287
TI  - Disinfection of dental unit waterlines with an oral antiseptic.
AB  - The problem of potential pathogens in biofilm within dental unit waterlines is
      real. Even though some chemical agents can disinfect biofilms, there remains
      concern that all remnants of the biofilm matrix are not eliminated, even with
      periodic treatments, and the bacterial populations in dental unit waterlines
      recur rapidly. Toxic and caustic residual chemicals are also a concern. In
      multiple trials following overnight treatment of dental unit waterlines with
      Listerine Antiseptic (LA), recurrence was investigated by evaluating effluent and
      biofilm specimens by plate culture. The presence or absence of biofilm within the
      dental unit waterlines was evaluated, pre- and post-treatment, by scanning
      electron microscopy. Baseline evaluations of dental unit waterlines determined
      the effluent and biofilm to harbor an average of 1 x 10(5) CFU per ml and 1 x
      10(4) CFU per cm2, respectively, prior to treatment. Overnight, 18-hour treatment
      with LA rendered effluent and biofilm samples free of recoverable bacteria in all
      cases immediately following treatment. Viable bacteria in the effluent of treated
      dental unit waterlines recurred to near pre-treatment levels by Day 7. The
      minimum inhibitory concentrations for each of the recovered isolates did not
      change following overnight treatment. Repeated overnight treatments at the
      beginning of a one-week study were effective in inhibiting recurrence of viable
      bacteria in the biofilm and effluent indefinitely, but still failed to completely
      remove the biofilm matrix. New tubing treated prior to use and then daily with LA
      did not develop a detectable biofilm by scanning electron microscopy during the
      study. One-month long follow-up clinical trials have demonstrated that a
      maintenance solution of a 1:50 concentration of LA and sterile distilled water in
      self-contained dental units with new tubing is effective for prolonged periods in
      maintaining the effluent within the American Dental Association's recommendation
      for the year 2000 of < 200 CFU per ml. The clinical significance of these
      findings is that a solution to the problem of dental unit waterline contamination
      may be currently available. Since antimicrobial LA is safe for patient use, it
      may be one of the most viable options suggested to date.

PMID- 11460288
TI  - An evaluation of resin-ionomers to prevent coronal microleakage in endodontically
      treated teeth.
AB  - While a gutta-percha system is most commonly used by practitioners for canal
      obturation, there is no agreement on how best to close the chamber of an
      endodontically treated tooth. Some materials used in restorative dentistry may
      have endodontic applications. Restorative materials of particular interest to
      endodontists are those used as subgingival restorations. Their properties include
      insolubility in oral fluids, adhesiveness, dual-cure capabilities, radiopacity,
      hardness and fluoride release, low cure shrinkage and a low coefficient of
      thermal expansion. The purpose of this in vitro study was to test three products
      that could be used to seal pulp chambers of endodontically treated teeth to
      prevent bacterial infiltration. A bacteriological assay system was used to
      determine the efficacy of three commercially available restorative materials to
      prevent penetration of Streptococcus salivarius from the pulp chambers into the
      prepared canals. The materials evaluated were: Geristore two-paste system with
      Tenure Quik with fluoride, Dispersalloy with Tenure Quik with fluoride, and
      Marathon posterior composite with Tenure Quik with fluoride. During the sixty
      days of the study, the analysis indicated that the Geristore two-paste system
      with Tenure Quik with fluoride provided a statistically significant improved seal
      when compared to the Marathon posterior composite and Dispersalloy amalgam with
      Tenure Quik with fluoride.

PMID- 11460289
TI  - Laboratory evaluation of two bi-level toothbrush products for subgingival access
      and gingival margin cleaning.
AB  - Recent technological advances have enabled the production of split or feathered
      endings of individual toothbrush filaments. The purpose of this laboratory study
      was to compare a bi-level manual toothbrush containing standard end-rounded
      bristles with the same shaped toothbrush containing feathered filaments, 3 mm
      deep, on the outer raised bi-level rows to achieve subgingival access (SA) and
      remove artificial plaque at the gingival margin, or gingival margin cleaning
      (GMC). Simulated gingivae were prepared with a 0.2 mm space between the gingivae
      and tooth surface. The toothbrushes were aligned with the papillae at the
      gingival margin, and were tested using wet brushing conditions for 60 seconds at
      two strokes per second with a 15 mm stroke. Four toothbrushes of each type were
      evaluated four times, for a total of 16 assays per design. The SA maximum depth
      was recorded on pressure-sensitive paper under the simulated gingivae, and the
      length of gingival margin cleaning was recorded as the GMC efficacy. Readings
      were performed with 3x magnification by one investigator. In these laboratory
      assays, the bi-level toothbrush with feathered outer-row bristles significantly
      (p < 0.001) increased the ability of the bristles to achieve SA by 35.7% and GMC
      efficacy by 54.5% compared to an identical bi-level toothbrush with end-rounded
      bristles.

PMID- 11460290
TI  - Clinical study of the effectiveness of two sonic toothbrushes.
AB  - The aim of this study was to determine the oral hygiene effects of two sonic
      toothbrushes, the Water Pik Sonic Speed (W) and Sonicare (S), compared to a
      manual toothbrush (Elmex Super 39, E). Thirty-six healthy volunteers between 13
      and 69 years of age participated in this single-blind, crossover study. They were
      randomly assigned to three groups, with 12 participants each. Two weeks after a
      screening examination, a baseline examination was performed for each participant
      followed by professional tooth cleaning. Three indices were recorded to assess
      the oral hygiene status: a papillary bleeding index (PBI), a plaque index for
      smooth surfaces (PI) and a plaque index for approximal surfaces (API). After
      instructions on how to use the toothbrushes, each group started the experiment
      with a different type of toothbrush. After two weeks of application, the indices
      were recorded a second time. This was followed by two weeks of recess, where each
      participant used the same brand of manual toothbrush, and then before each group
      switched to the next toothbrush, participants had another baseline examination
      and professional tooth cleaning. The three types of brushes were used in the
      following order: S, E, W; recess; E, W, S; recess; W, S, E. The duration of the
      study was 12 weeks. A single investigator performed all examinations. The
      Friedman test and Wilcoxon signed rank test were used for statistical analysis.
      Compared to the manual toothbrush the Sonic Speed and the Sonicare were more
      effective in removing plaque and preventing gingivitis. The study indicated that
      the two sonic toothbrushes may be effective alternatives to a commonly used
      manual toothbrush.

PMID- 11460291
TI  - An in situ study on the comparison of fluoride uptake and bond strength of
      composite resin on fluoridated enamel.
AB  - The aim of this in situ study was to compare the fluoride uptake and composite
      resin bond strength on enamel fluoridated with Duraphat (2.26 wt% fluoride). Six
      enamel specimens were prepared from the labial surfaces of 39 bovine incisors.
      The enamel samples were embedded into epoxy resin, and ground flat (800 grit).
      One specimen served as negative control (no fluoride treatment). The other
      samples were fluoridated with Duraphat for 24 hours under moist conditions, and
      one of them served as positive control. The remaining four samples were inserted
      in both buccal aspects (with a total of 12 samples originating from 3 teeth) of
      13 intraoral mandibular appliances. The appliances were worn by 13 persons for a
      period of 6 days, 24 hours per day. The samples were also brushed twice a day, in
      situ, with a fluoride-free toothpaste. During meals, the appliances were stored
      in saline. After in situ periods of 36, 72, 108, and 144 hours, three samples
      each were remounted. One specimen was used for analysis of both alkali-soluble
      and acquired fluoride. The other two specimens served for shear bond strength
      testing of a light-cured composite resin. While the KOH-soluble fluoride
      increased significantly (p < 0.001, ANOVA) after application of the fluoride
      lacquer and decreased slowly with time, both the acquired fluoride and bond
      strengths of the composite resin did not differ significantly from the non- and
      fluoridated controls. The application of highly concentrated fluoride lacquers
      results in an increase of alkali-soluble fluoride, but does not adversely affect
      enamel bond strength of composite resin.

PMID- 11460292
TI  - Ryan White CARE Act Title IV: building networks to improve healthcare delivery to
      the HIV infected.
AB  - There has been little evaluation of the implementation of HIV consortia that were
      created under Title IV of the Ryan White Comprehensive AIDS Resources Emergency
      (CARE) Act. In 1993, Mor and colleagues reported that the effectiveness of
      networks established by the Robert Wood Johnson Foundation had been compromised
      by the inability of the participating agencies to work together, given their
      competing goals and varied institutional cultures. In a study published in 1995,
      Roy and colleagues identified the following as determinants of successful project
      implementation: federal and local government support, management-level support
      and technical assistance, and linkages between participating agencies. This
      article describes the role that network infrastructure can play in developing
      interagency collaboration, and the importance of network infrastructure in
      coordinating the delivery of care at the service-delivery level. The authors
      describe the efforts of the Lower New York Consortium for Families with HIV
      (hereafter, "the Consortium") to develop integrative mechanisms at both the
      network level and the program level. As the number of infected women grows, so
      does the need to improve the delivery of services and to reduce barriers to the
      receipt of care. In itself, the support of individual agencies that provide case
      management services may not be enough to improve service delivery and reduce
      barriers; the experiences of networks such as the Consortium may help inform the
      development of guidelines for creating and enhancing the coordination of services
      to assure improvements in care. Systematic studies are needed to evaluate
      different models of collaboration and of coordinating care to determine whether
      the effort to develop consortia is justified by improved access to care and
      improved health.

PMID- 11460293
TI  - The effectiveness of resource allocation methods used by RWCA Title II Consortia
      in Virginia.
AB  - The authors sought to determine the following: (1) How rigorous are the current
      resource allocation methods used by Virginia's five regional Ryan White CARE
      (Comprehensive AIDS Resources Emergency) Act Title II consortia? (2) How useful
      are existing databases in allocating resources? (3) Is it feasible to introduce a
      standardized performance measurement approach for state-level assessment of
      consortia effectiveness? The authors reviewed proposals and progress reports from
      each of the consortia to the Virginia public health agency; they then visited
      each of the consortia to solicit information to refine the study questions and to
      review the consortia's databases. The authors reviewed the literature on existing
      models used to allocate resources, and surveyed members of the Virginia consortia
      about how they used various resource allocation tools, how effective these tools
      were, and how ready the consortia were to be evaluated regarding resource
      allocation. The authors found no uniform process for the allocation of Title II
      funds in Virginia. Consortia members who felt connected and involved with their
      consortium were significantly more knowledgeable about its operations and more
      likely to consider it effective. A consortium's use of a continuous quality
      improvement (CQI) approach to allocating resources was strongly associated with
      its members' perception that the consortium was effective. Statewide performance
      and/or outcome measures cannot be set without some standardized expectations for
      performance. To do this, some expectations for basic resource allocation
      procedures must be established. Three of Virginia's five consortia will make use
      of this study's instrumentation in their next resource allocation processes, and,
      if their experiences are useful, a statewide process may be established. If a
      statewide process is established, regional consortia must continue to be able to
      determine local needs and to respond with locally appropriate service planning.

PMID- 11460294
TI  - Hong Kong: an epicenter of increasing risk for HIV transmission? Overview and
      response.
AB  - Hong Kong, a Special Administrative Region (HKSAR) of the Peoples' Republic of
      China (PRC), has a low prevalence of HIV infection. This has been attributed to
      an extensive prevention and control program implemented by the Hong Kong
      government from the very beginning of the epidemic. Since the early 1990s, HIV
      related surveys in Hong Kong have delineated the magnitude of the problem and
      identified particularly relevant cultural features that both increase and limit
      the risk of the transmission of HIV. Factors that may increase transmission
      include high rates of regional travel, cross-border mobility, and growing
      commercial sex industries nearby; the latter two are particularly important.
      Protective factors may include a later age for first sexual experience than in
      Western countries. More epidemiological research, and particularly intervention
      research, is needed in the HKSAR to identify new means to maintain the current
      low HIV/AIDS prevalence and to further strengthen prevention and control
      programs. Collaboration between government bodies, non-government organizations,
      and researchers is needed to assure that the best programs and policies are
      identified and implemented.

PMID- 11460295
TI  - History of facial nerve surgery.
AB  - The history of facial nerve surgery can be viewed as five overlapping periods,
      each characterized by a new understanding or approach to the management of facial
      nerve conditions. The first period, the period of discovery of the nerve of
      facial expression, began with Sir Charles Bell's description in 1829 of 3 cases
      of facial paralysis due to facial nerve trauma. The second period, from 1873 to
      1960, was the era of facial nerve repair. Decompression of the facial nerve was
      the primary focus of facial nerve surgery in the third period, from 1908 to 1969.
      The fourth period, from 1970 to 2000, can be characterized as the "bottleneck"
      period in honor of the contributions to facial nerve surgery that resulted as Ugo
      Fisch and other surgeons sought ways to operate on this portion of the proximal
      nerve. In the current or fifth, period in the history of facial nerve surgery, we
      anticipate the advent of vaccines and antiviral medications to minimize the
      sequelae of Bell's palsy, further improvements in endoscopic equipment and
      techniques, and better surgical outcomes through the use of new technologies such
      as robotics.

PMID- 11460296
TI  - Facial nerve repair: a retrospective review.
AB  - The purpose of this article is to review a large series of patients evaluated for
      disorders of the facial nerve in order to assess the indications for surgery, the
      timing of surgery, the techniques of nerve repair, and to better define those
      factors associated with a favorable outcome. STUDY DESIGN: A retrospective review
      of patients undergoing facial nerve repair from 1963-1997. METHODS: One hundred
      and three patients underwent surgical intervention designed to repair a disrupted
      facial nerve. All procedures were performed by one of the senior surgeons (M.M.)
      Seventy-two patients had a complete data set and at least one year of follow-up.
      RESULTS: Eighty percent of patients attained an outcome considered superb to
      fair. Twenty percent of patients had a poor outcome. There was a slight worsening
      of outcome with increased time to repair. Patients with a neoplastic etiology of
      nerve paralysis tended to have a worse outcome. CONCLUSIONS: Facial nerve
      grafting is most successful if intervention is undertaken at or near the time of
      initial injury. However, prolonged time (up to two years) to repair does not
      preclude the potential for some recovery. The limitations of the current systems
      for grading facial recovery after nerve repair are well known, and the adoption
      of a new grading scale for assessing recovery after reanimation procedure is
      recommended.

PMID- 11460297
TI  - Facial nerve grading systems.
AB  - Clinicians require a reliable and sensitive facial grading system to determine
      the status of facial nerve function postinjury as well as to evaluate the
      efficacy of treatment outcomes. The method of assessment should be easy to
      administer, reproducible, clinically relevant, and require little time and
      expense. The grading system should be sufficiently sensitive to detect changes
      over time or following treatment. The lack of a universally accepted grading
      system frequently does not allow meaningful comparison when assessing the
      effectiveness of treatment protocols for facial nerve injury. The aim of this
      article is to review most of the previously published facial grading systems. It
      is our contention that a grading system developed and currently used within our
      institution appropriately addresses the needs as well as many of the deficiencies
      of most other grading systems.

PMID- 11460298
TI  - Reanimation of the paralyzed eyelid with the enhanced palpebral spring or the
      gold weight: modern replacements for tarsorrhaphy.
AB  - The enhanced palpebral spring and the gold weight are the modern devices that
      should nearly completely replace tarsorrhaphy in the management of ocular
      problems secondary to facial paralysis. They actually reanimate the lid, rather
      than merely hold the lids closed in a disfigured position, as does tarsorrhaphy.
      The surgical techniques of each procedure, results, and pros and cons of each are
      compared. Personal experience with over 1400 spring implantations is discussed,
      as is experience with the use of bandage contact lenses in lieu of lid surgery.
      The gold weight implantation is simpler to learn and perform than the enhanced
      spring procedure, in which the levator is tightened in addition to implanting the
      spring. However, when it is really important to close the eye well, the spring is
      the superior procedure. Unlike the weight, the spring closes the eye well in the
      supine position, such as when the patient sleeps.

PMID- 11460299
TI  - Restoration of lower eyelid support in facial paralysis.
AB  - Lower eyelid dysfunction in the patient with facial paralysis is frequently the
      result of several deleterious factors, including the loss of orbicularis tone,
      involutional changes in the canthal ligaments, the effect of aging on the
      midfacial soft tissue structures, and malposition of the lower eyelid punctum.
      This dysfunction is manifested as lagophthalmos, ectropion, and epiphora.
      Fortunately, there are several surgical methods by which the various
      abnormalities can be corrected or compensated for. This article addresses the
      management of the lower eyelid and several of the current methods available to
      the surgeon for management of the lower eyelid in facial paralysis.

PMID- 11460300
TI  - The SOOF lift as an adjunct in rehabilitation of facial paralysis: help or hype?
AB  - Rehabilitation of the midface in chronic facial paralysis is one of the last
      frontiers in global facial reanimation. The suborbicularis oculi fat pad lift, or
      SOOF lift, also known as the midface lift, has been popularized in aesthetic
      surgery literature as a way to restore midface fullness with a youthful
      appearance while eliminating midface sag associated with aging. These techniques
      of midface aesthetic rejuvenation have recently been applied in cases of chronic
      facial paralysis. This article analyzes the role of the midface lift or SOOF lift
      in cases of facial reanimation and determines whether or not it is of benefit to
      patients affected by chronic facial paralysis.

PMID- 11460301
TI  - Temporalis muscle transfer for facial paralysis: a further refinement.
AB  - Facial nerve paralysis can occur due to failure of the central driving mechanism
      (nuclear or supranuclear pathology), failure of the conduit between the brainstem
      and the peripheral musculature (the facial nerve), or failure of the peripheral
      end organ (the neuromuscular system). Where the peripheral neuromuscular system
      fails, the options for dynamic reanimation include a regional muscle transfer
      driven by another ipsilateral cranial nerve, or a free muscle transfer driven by
      the contralateral facial nerve. Temporalis muscle transfer is an example of
      regional muscle transfer and has been used since early in the twentieth century.
      A further refinement, involving mobilization of the coronoid process of the
      mandible in continuity with the insertion of the temporalis muscle via a
      nasolabial fold approach, using fascial strips to re-create movement around the
      mouth, is presented.

PMID- 11460302
TI  - Facial reanimation with microneurovascular free flaps.
AB  - Numerous options are available for rehabilitation of chronic facial nerve
      paralysis, ranging from simple slings to complex procedures such as
      microneurovascular tissue transfer. Microneurovascular muscle transfer is
      generally indicated: 1) if the patient desires dynamic facial reanimation,
      particularly restoration of involuntary emotional facial expressions; 2) in the
      absence of distal facial nerve fibers or motor endplate function; 3) with an
      associated large soft tissue defect in the cheek; and 4) when other dynamic
      reanimation procedures have not been successful. The most commonly used free
      flaps for facial reanimation are gracilis, latissimus dorsi and inferior rectus
      abdominus muscle. When successfully performed free flaps yield excellent
      functional and aesthetic results in facial reanimation.

PMID- 11460303
TI  - Facial paralysis: is there a role for a therapist?
AB  - Rehabilitation for peripheral facial paralysis is often neglected and patients
      are left untreated. This article explains how nonsurgical rehabilitation,
      specifically facial neuromuscular retraining, restores function in these
      patients. Patients with facial paralysis resulting from viral causes,
      postsurgical tumor resection, traumatic injury, or congenital paresis may be
      candidates for treatment. Typical patients present with flaccid paralysis acutely
      and may develop abnormal movement patterns (synkinesis) as recovery progresses.
      Neuromuscular retraining is effective. It provides specific strategies that
      inhibit synkinesis based on individual function and unique facial nerve and
      muscle properties. Successful rehabilitation results in improved patient
      satisfaction, self-esteem, and quality of life. Electrical stimulation should not
      be used at any time in facial rehabilitation. There is evidence that it may be
      contraindicated, and it is unnecessary. The imperative in treating synkinesis is
      to inhibit abnormally contracting muscles, not stimulate flaccid ones. The
      unfounded use of electrical stimulation is an unnecessary expense for patients
      and third-party payers.

PMID- 11460304
TI  - Effects of tumor necrosis factor-alpha, epidermal growth factor and transforming
      growth factor-alpha on interleukin-8 production by, and human rhinovirus
      replication in, bronchial epithelial cells.
AB  - Previous studies have shown that the epidermal growth factor (EGF) and
      transforming growth factor-alpha (TGF-alpha), members of the EGF growth factor
      family, regulate processes involved in airway repair after injury. Our studies
      were conducted to determine whether EGF and TGF-alpha directly control processes
      involved in the pathogenesis of airway inflammation and/or modulate the
      inflammatory effects of TNF-alpha in the airway mucosa. We have found that these
      cell growth factors directly induced interleukin-8 (IL-8) production by an
      immortalized human bronchial epithelial cell line (BEAS-2B cells). Furthermore,
      EGF and TGF-alpha enhanced tumor necrosis factor-alpha (TNF-alpha) induced IL-8
      production by BEAS-2B cells. On the other hand, EGF but not TGF-alpha increased
      viral replication by BEAS-2B cells exposed to HRV-14. Moreover, TNF-alpha
      increased viral replication in the presence of EGF but not TGF-alpha. In
      conclusion, this study demonstrates that both EGF and TGF-alpha play an active
      role in the pathogenesis of airway inflammation.

PMID- 11460305
TI  - Ex vivo analysis of tumor antigen specific CD8+ T cell responses using
      MHC/peptide tetramers in cancer patients.
AB  - The development of soluble tetrameric MHC/peptide complexes has opened the
      possibility to directly identify and monitor antigen-specific CD8+ T cells in
      different clinical situations. This represents a technological breakthrough for
      the field of cell-mediated immunity. For example, the direct identification and
      enumeration of tumor-specific CD8+ T cells at the tumor site and in blood has
      recently provided compelling evidence that strong anti-tumoral responses
      naturally occur in some cancer patients. Moreover, the use of tetramers plays an
      essential role in the design of vaccination protocols aimed at inducing a strong
      and protective CD8+ T cell-mediated anti-tumoral response in cancer patients. The
      monitoring of antigen-specific T cell responses elicited by various peptide-based
      vaccines tested in phase I clinical trials clearly indicates that tumor-specific
      CD8+ T cells can be activated effectively at least in some cancer patients. Thus,
      multiparameter monitoring of antigen-specific T cell responses that combines ex
      vivo tetramer staining with various phenotyping and functional assays provides a
      novel approach to assess the functional potential of tumor-specific T lymphocytes
      and may also facilitate the optimization of vaccination protocols.

PMID- 11460306
TI  - Development of immunoadjuvants for immunotherapy of cancer.
AB  - Previously, we have reported that cell-wall skeleton (CWS) fraction was the major
      adjuvant-active principle of mycobacterial cells which were used in Freund's
      complete adjuvant (FCA). We have described the biochemical and immunological
      properties of CWS of mycobacteria and related bacteria, especially the CWS of
      Mycobacterium bovis BCG strain (BCG-CWS) in detail. The effectiveness of BCG-CWS
      for the cancer immunotherapy in patients was shown in several clinical trials. On
      the action mechanism of BCG-CWS on host immune cells, we have suggested that
      dendritic cells and macrophages express two sorts of receptors, Toll-like
      receptors, TLR-2 and TLR-4, and a putative binding receptor for BCG-CWS, whose
      signaling pathways lead to a sufficient antigen-presenting state in the
      activation of the innate immune system. We have also reported the usefulness of
      synthetic immunoadjuvants such as muramyldipeptide (MDP) derivatives, trehalose
      dimycolates (TDM) and DNA fraction for the application for the cancer and
      infectious diseases in experimental systems and cancer patients.

PMID- 11460307
TI  - Extrathymic pathways of T-cell differentiation and immunomodulation.
AB  - It is well established that the thymus is an essential organ for the support of T
      cell differentiation. However, some T cells, termed extrathymic T cells, have
      been found to differentiate without such support by the thymus. The major sites
      of these T cells are the intestine and liver. Subsequent studies have revealed
      that extrathymic T cells are also present in the uterus and exocrine glands
      (e.g., the salivary gland). Depending on the sites, extrathymic T cells have some
      distinct properties as well as some common properties. For example, all
      extrathymic T cells have a TCR-CD3 complex similar to thymus-derived T cells.
      Extrathymic T cells comprise both alpha beta T cells and gamma delta T cells.
      Although extrathymic T cells are very few in number at any extrathymic sites in
      youth, they increase in number as a function of age. This phenomenon seems to
      occur in parallel with thymic involution. Even in youth, extrathymic T cells are
      activated in number and function by stress, in autoimmune diseases, and during
      pregnancy. Acute thymic atrophy always accompanies this activation. Therefore,
      reciprocal regulation between extrathymic T cells and thymus-derived T cells
      might be present. We hypothesize that extrathymic T cells are intimately
      associated with innate immunity and that the mechanisms underlying autoimmune
      diseases and intracellular infection (e.g., malaria) cannot be properly
      understood without introducing the concept of extrathymic T cells.

PMID- 11460308
TI  - Acemannan purified from Aloe vera induces phenotypic and functional maturation of
      immature dendritic cells.
AB  - Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have
      antiviral and antitumoral activities in vivo through activation of immune
      responses. The present study was set out to define the immunomodulatory activity
      of acemannan on dendritic cells (DCs), which are the most important accessory
      cells for the initiation of primary immune responses. Immature DCs were generated
      from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM
      CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS,
      respectively. The resultant DCs were examined for phenotypic and functional
      properties. Phenotypic analysis for the expression of class II MHC molecules and
      major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that
      acemannan could induce maturation of immature DCs. Functional maturation of
      immature DCs was supported by increased allogeneic mixed lymphocyte reaction
      (MLR) and IL-12 production. The differentiation-inducing activity of acemannan
      was almost completely abolished by chemical sulfation. Based on these results, we
      propose that the adjuvant activity of acemannan is at least in part due to its
      capacity to promote differentiation of immature DCs.

PMID- 11460309
TI  - Effect of Salmonella-infected human monocytes on natural killer cell
      cytotoxicity. In vitro studies.
AB  - Various chemicals, including some bacteria-derived components, modulate natural
      killer cell (NKC) activity. We have analyzed the effect of wild-type Ty2 and of
      mutant strain TYT1231 Salmonella typhi-infected monocytes (U937 cells and human
      autologous monocytes) on NKC cytotoxicity of peripheral blood mononuclear cell
      (PBMC) and highly purified NKC (HPNKC; CD16+/56+ > 95%; the rest corresponding to
      CD3+ T-cells). PBMC's co-culture with either S. typhi strain infected U937 cells
      (medium or non-infected U937 cells as controls) resulted in the induction of
      lymphocyte activated killer (LAK) cell activity showing cytotoxicity against
      target human NKC-resistant lymphoblastoid Daudi cell line. Comparable experiments
      using autologous monocytes gave similar results. Co-culture of HPNKC preparations
      with either S. typhi strain infected U937 cells resulted in increased LAK cell
      activity against target Daudi cells in each and everyone of the five samples
      tested; paired Student's t-test p < 0.01 for both times (20 and 40 h) tested.
      Similar to the results observed in the experiments using PBMC, we did not find
      significant differences in the ability between medium and non-infected cells, or
      between wild-type S. typhi Ty2 and mutant strain TYT1231 infected U937 cells, to
      induce LAK activity in HPNKC preparations. PBMC co-incubation with either S.
      typhi strain infected U937 cells or autologous monocytes resulted in significant
      increases in IL-12, TNF-alpha, and IFN-gamma secretion. In similar experiments
      using HPNKC samples instead, infected U937 cells significantly increased IL-12
      and IFN-gamma, but not TNF-alpha secretion. PBMC co-incubation with non-infected
      U937 cells, but not with non-infected monocytes, significantly increased
      supernatant IL-12 and TNF-alpha levels (no significant changes in IFN-gamma were
      recorded). Secreted cytokines remained essentially unchanged after co-incubating
      HPNKC preparation with non-infected U-937 cells. Incubation of PBMC or HPNKC
      preparations with either S. typhi strain infected U937 cells failed to produce
      significant changes in the expression of NKC lineage (CD16+/56+) or activation
      (CD28+, CD69+ and CD95+) markers. The ability of infected monocytes to induce LAK
      activity, release NKC cytokines and upmodulate NKC's CD95+ marker expression was
      essentially the same for both infecting Salmonella strains used. These results
      suggest a role for NKC in the physiological defensive response against
      intracellularly infected monocytes representing, perhaps one of the earliest
      antimicrobial mechanisms of the innate immune system.

PMID- 11460310
TI  - Long-term intake of Korean red ginseng in HIV-1-infected patients: development of
      resistance mutation to zidovudine is delayed.
AB  - We have observed that CD4+ T cell counts in human immunodeficiency virus (HIV)-1
      infected patients treated with only Korean red ginseng (KRG) are maintained or
      even increased for a prolonged period. In the present study, we investigated
      whether the development of resistance mutations in reverse transcriptase (RT) to
      zidovudine (ZDV) is delayed by combined therapy with KRG and ZDV. Nested
      polymerase chain reaction (PCR) and direct sequencing methods were used to define
      RT codons 41, 67, 70, 210, 215 and 219 of the HIV-1 pol gene in DNA from
      peripheral blood mononuclear cells (PBMC) samples from 18 patients. Nine of these
      eighteen patients were in the KRG group and had been treated with KRG for 60 +/-
      15 months (range: 38-82) and ZDV, and nine were in the control group and had been
      treated with ZDV only. The patients in the KRG group had been treated with ZDV
      for 75 +/- 24 months, and CD4+ T cell counts were maintained from 239 +/- 85 to
      234 +/- 187 microliters-1 (P > 0.05) during the study period, whereas the
      patients in the control group had been treated with ZDV for 51 +/- 31 months, and
      their CD4+ T cell counts decreased from 272 +/- 97 to 146 +/- 154 microliters-1
      (P < 0.01). In samples within 24 months of ZDV therapy, the overall incidence of
      6 resistance mutations to ZDV was 4.2% and 47% in the KRG and control group (P <
      0.01), respectively. In samples after 24 months of therapy, the incidence was
      21.7% and 56.3% in the KRG and control group (P < 0.01), respectively. These data
      suggest that the maintenance of CD4+ T cell counts by ZDV and KRG-intake for a
      prolonged period might be indirectly associated with delayed development of
      resistance to ZDV by KRG-intake.

PMID- 11460311
TI  - Activation-induced T cell apoptosis by monocytes from stem cell products.
AB  - We recently found that mobilized peripheral blood stem cell (PSC) products (from
      both cancer patients and normal donors) contain high levels of CD14+ monocytes,
      which can inhibit the proliferation of allogeneic and autologous T cells. We
      found in our studies that using CD14+ monocytes from mobilized PSC products (from
      normal and cancer patient donors), normal apheresis products or normal peripheral
      blood (PB) can affect lymphocyte function and apoptosis-dependent T cell
      activation. However, it appears that the apoptosis is dependent on the frequency
      of monocytes, which is increased by both mobilization and apheresis. Both
      phytohemagglutinin (PHA)- and interleukin (IL)-2-induced proliferation of steady
      state peripheral blood mononuclear cells (PBMC) were markedly inhibited by co
      culture with irradiated CD14+ monocytes, although inhibition was significantly
      greater with PHA than with IL-2 stimulation. IL-2 (predominately CD56+ NK cells)
      or anti-CD3 monoclonal antibody (mAb) and IL-2-expanded lymphocytes (activated T
      cells) were inhibited by PSC monocytes to a significantly greater level as
      compared to steady-state lymphocytes. Indeed, no inhibition of T cell
      proliferation was observed when lymphocytes were co-cultured in the absence of
      mitogenic or IL-2 stimulation. In contrast, an increased proliferation was
      observed in co-cultures of CD14+ monocytes and steady-state or activated
      lymphocytes without mitogenic stimulation. Cell cycle analysis by flow cytometry
      revealed a significant increase in hypodiploid DNA, in a time-dependent manner,
      following co-culture of monocytes and PBMC in PHA, suggesting that T cell
      apoptosis occurred during PHA-induced activation. These results demonstrate that
      PSC-derived monocytes inhibit T cell proliferation by inducing the apoptosis of
      activated T cells and NK cells, but not steady-state cells. This suggests a
      potential role for monocytes in the induction of peripheral tolerance following
      stem cell transplantation.

PMID- 11460312
TI  - Similar effects of ether phospholipids, PAF and lyso-PAF on the Ca(2+)-ATPase
      activity of rat brain synaptosomes and leukocyte membranes.
AB  - The present study is an extension of our previous work with the antineoplastic
      ether phospholipid ET-18-OCH3 (edelfosine), which was shown to affect the
      activity of the Ca(2+)-ATPase of rat brain synaptosomes and peritoneal leukocyte
      membranes. The effect of ET-18-OCH3 was compared with that of the 16-carbon chain
      analogue ET-16-OCH3 as well as with the structurally related 16- and 18-carbon
      PAFs (platelet-activating factors) and lyso-PAFs. In addition, the two
      alkylphosphocholines D-20166 and D-21266 (perifosine) were included in the
      investigation. The influence of all of the compounds followed the same pattern,
      i.e., the Ca(2+)-ATPase activity of the synaptosomes was increased over a
      relatively narrow concentration range (peak at 20-30 microM) and that of the
      leukocyte membranes was inhibited in a concentration-dependent manner by 10-50
      microM concentrations of the drugs. Ether phospholipids with an 18-carbon chain
      at C-1 were more potent than those with a 16-carbon chain. All of the compounds
      increased the activity of the synaptosomal ATPase to the same extend (ca. 50%).
      With the exception of lyso-PAF, all inhibited the enzyme activity of leukocyte
      membranes by 60-70%, whereas lyso-PAF was less effective (ca. 50% inhibition).
      The concentration range of activity for PAF and lyso-PAF indicates that their
      effect on the enzyme activity was caused by receptor-independent mechanisms. The
      ether phospholipids and alkylphosphocholines are suggested to act by accumulating
      in the membranes and thereby altering the character of the lipid environment of
      the enzyme rather than by a direct interaction with the Ca(2+)-ATPase.

PMID- 11460313
TI  - Experimental evidences and signal transduction pathways involved in the
      activation of NF-kappa B/Rel by angelan in murine macrophages.
AB  - In our previous studies, we showed that angelan, a polysaccharide purified from
      Angelica gigas Nakai, activated macrophages to induce the translocation of NF
      kappa B/Rel into nucleus and DNA binding to its cognate site in the promoter of
      iNOS gene [Immunopharmacology 43 (1999) 1; Immunopharmacology 49 (2000) 275]. In
      the present study, we showed that angelan induces the transcriptional activation
      of NF-kappa B/Rel and investigated the intracellular signal transduction pathways
      involved in the angelan-induced NF-kappa B/Rel activation by murine macrophages.
      Treatment of RAW 264.7 cells with angelan resulted in significant activation of
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38, while stress
      activated protein kinase/c-Jun NH2 terminal kinase (SAPK/JNK) was not activated
      by angelan. The specific p38 inhibitor SB203580 abrogated the angelan-induced NF
      kappa B/Rel activation, whereas the selective MAPK/extracellular signal-regulated
      kinase 1 (MEK-1) inhibitor PD98059 did not affect the NF-kappa B/Rel induction.
      Treatment of RAW 264.7 cells with both anti-CD14 Ab and anti-CR3 Ab significantly
      blocked angelan-induced NF-kappa B/Rel activation. In conclusion, we demonstrate
      that angelan induces NF-kappa B/Rel activation through the CD14 and CR3 membrane
      receptor and p38 kinase that is critically involved in the signal transduction
      leading to NF-kappa B/Rel activation in murine macrophages.

PMID- 11460314
TI  - Mechanisms and modulation of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced
      Ca2+ mobilization in human neutrophils.
AB  - The effect of fMLP (N-formyl-methionyl-leucyl-phenylalanine), a neutrophil
      stimulating bacterial peptide, on Ca2+ mobilization in human neutrophils was
      examined using fura-2 as a Ca2+ indicator. fMLP (10 nM-10 microM) increased
      [Ca2+]i concentration-dependently. The [Ca2+]i signal comprised an initial rise
      followed by a gradual decay and a sustained phase. External Ca2+ removal partly
      decreased the signal. La3+ (50 microM) pretreatment mimicked the effect of Ca2+
      removal. In Ca(2+)-free medium, pretreatment with 1 microM thapsigargin (an
      endoplasmic reticulum Ca2+ pump inhibitor) prevented 10 microM fMLP from
      increasing [Ca2+]i; whereas 1 microM thapsigargin still significantly increased
      [Ca2+]i after pretreatment with 10 microM fMLP. Addition of 3 mM Ca2+ induced a
      concentration-dependent [Ca2+]i increase after pretreatment with fMLP in Ca(2+)
      free medium. This Ca2+ entry was partly inhibited by econazole (25 microM),
      SKF96365 (50 microM), and a phospholipase A2 inhibitor (aristolochic acid; 20
      microM). The fMLP (10 microM)-induced Ca2+ release was abolished by inhibiting
      phospholipase C with 2 microM U73122. The fMLP-induced [Ca2+]i increase was
      inhibited by 25% by pretreatment with 10 nM phorbol ester to activate protein
      kinase C but was augmented by 27% by pretreatment with 2 microM GF 109203X to
      inactivate protein kinase C. We found that fMLP increase reactive oxygen
      intermediate (ROI) production in neutrophils, which can be suppressed by U73122
      pretreatment. Collectively, this study shows that in human neutrophils, fMLP
      increased [Ca2+]i concentration-dependently by releasing Ca2+ from phospholipase
      C-coupled, thapsigargin-sensitive stores, accompanied by Ca2+ entry. The fMLP
      induced [Ca2+]i rise was modulated by protein kinase C, and the fMLP-induced Ca2+
      entry was abolished by La3+, and was reduced by econazole, SKF96365 and
      inhibition of phospholipase A2.

PMID- 11460315
TI  - Signal transduction pathways in directed migration of human monocytes induced by
      human growth hormone in vitro.
AB  - The human growth hormone (GH) was shown to modulate leukocyte functions such as
      stimulating directed migration of human monocytes in vitro. Dimerisation of GH
      receptors leads to the activation of various signalling mechanisms. As
      transduction of GH signals to monocytes is unknown, we investigated GH signalling
      mechanisms in monocyte migration using a modified Boyden chamber chemotaxis
      assay. Inhibition of tyrosyl phosphorylation of GH receptor-associated tyrosine
      kinase by tyrphostin-23 or staurosporine blocked GH-stimulated monocyte migration
      down to random levels. Furthermore, pre-incubation with effective concentrations
      of 4B-phorbol-12-myristate-13-acetate (PMA), staurosporine and
      bisindolylmaleimide I, inhibitors of protein kinase C, significantly decreased GH
      induced migration, suggesting that PKC is involved in the signalling cascade.
      Additionally, phosphatidylinositol 3-kinase and mitogen-activated protein kinase
      (MAPK) activation seems to be required. This study revealed signalling pathways
      in monocyte movement toward GH in vitro.

PMID- 11460316
TI  - Circulating dopamine level, in lung carcinoma patients, inhibits proliferation
      and cytotoxicity of CD4+ and CD8+ T cells by D1 dopamine receptors: an in vitro
      analysis.
AB  - Besides cardiovascular and renal functions, the role of dopamine in periphery as
      an endogenous regulator of immune functions is in the limelight. In human
      malignancy, depression of T cell functions is known. Interestingly, recent
      evidences indicate significant elevation of plasma dopamine in malignancy due to
      stress of the disease process. Therefore, this study evaluates whether this
      increased plasma dopamine exerts any influence on the proliferation and
      cytotoxicity of CD4+ and CD8+ T cells. Patients with lung carcinoma were selected
      for this study due to the high prevalence rate of this kind of cancer in
      developing countries and also due to strong positive biochemical and
      psychological criteria of stress in most of the patients. Results showed
      significant elevation of plasma dopamine (48.6 +/- 5.1 pg/ml) in lung cancer
      patients than normal controls (10.2 +/- 0.9 pg/ml). In vitro dopamine
      concentration, simulating the plasma concentration of the patients, significantly
      inhibited the proliferation and cytotoxicity of T cells of these patients and
      also of the normal volunteers, in presence of their respective serum. The
      mechanism has been attributed to be D1 class of dopamine receptor mediated
      elevation of intracellular cAMP in these cell populations. The results may be of
      significance in understanding the role of peripheral dopamine as an
      immunomodulator in human health and diseases.

PMID- 11460317
TI  - Phosphatidylcholine-specific phospholipase C and D in stimulation of RAW264.7
      mouse macrophage-like cells by lipopolysaccharide.
AB  - The purpose of these studies was to identify the role of phospholipases in the
      activation of macrophages by lipopolysaccharide (LPS). Tricyclodecan-9-yl
      xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipase C
      (PC-PLC); butanol, an inhibitor of phosphatidylcholine phospholipase D (PC-PLD);
      and propranolol, an inhibitor of phosphatidate phosphohydrolase, were used in the
      study. Treatment of RAW264.7 murine macrophage-like cells with LPS resulted in
      expression of inducible nitric oxide synthase and tumor necrosis factor-alpha.
      The expression was partially inhibited by D609, butanol, or propranolol and was
      completely blocked by the combination of D609 and butanol. RAW264.7 cells
      constitutively produced low basal levels of diacylglycerol and phosphatidic acid;
      production of both was significantly increased after stimulation with LPS,
      reaching a peak in 2-3 min and remaining elevated after 30 min. In LPS-induced
      RAW264.7 cells, diacylglycerol was suppressed by each of the three inhibitors
      alone and almost abolished by D609 plus butanol or D609 plus propranolol.
      Phosphatidic acid was reduced to basal level by butanol after LPS stimulation for
      2.5 min and by butanol plus D609 after LPS stimulation for 2.5 or 10 min. Taken
      together, these data indicate that activation of RAW264.7 cells by LPS can be
      mediated by the activities of both PC-PLC and PC-PLD.

PMID- 11460318
TI  - Suppression of co-stimulatory molecule expressions on splenic B lymphocytes by a
      macrolide antibiotic, roxithromycin in vitro.
AB  - The influence of a macrolide antibiotic, roxithromycin (RXM), on co-stimulatory
      molecule expression was examined using in vitro cell culture technique. Spleen
      cells obtained from BALB/c mice 10 days after immunization with 8.0 micrograms of
      haemocyanin absorbed to 4.0 mg aluminum hydroxide were cultured in the presence
      of 100.0 micrograms/ml haemocyanin and various concentrations of RXM for 72 h.
      Low concentrations (1.0 and 2.5 micrograms/ml) of RXM did not influence cell
      activation induced by antigenic stimulation, whereas RXM showed a suppressive
      effect on blastic activity of the cells when the agent was added to the cultures
      at more than 5.0 micrograms/ml. RXM did not affect blastic activity of splenic T
      cells by anti-CD3 monoclonal antibody stimulation even when the cells were
      cultured in the presence of 10.0 micrograms/ml RXM. Addition of anti-CD80 and
      anti-CD86 monoclonal antibody to cell cultures caused significant suppression of
      cell activation by antigenic stimulation. We next examined the influence of RXM
      on co-stimulatory molecule expressions on splenic B cells in response to
      antigenic stimulation. Addition of RXM at a concentration of 5.0 micrograms/ml
      into cell cultures remarkably suppressed co-stimulatory molecule, CD40, CD80 and
      CD86, expressions, which enhanced by antigenic stimulation in vitro.

PMID- 11460319
TI  - Photocatalytic degradation of trans-cinnamic, dihydrocinnamic, trans-caffeic, and
      dihydrocaffeic acids and characterization of the products.
AB  - Catalysed degradation of aqueous solutions of cinnamic 1, dihydrocinnamic 2,
      dihydrocaffeic 3 and trans-caffeic 4 acids in the presence of (TiO2) and UV
      radiation and the products identified by HPLC, and after treatment with
      diazomethane by GC-MS have been studied. A pH range of 3 to 11 was used. The four
      acids, in the presence of TiO2 in the dark, underwent little degradation.
      Extended irradiation of all the acids in the presence of TiO2 produced complete
      degradation as shown by TOC measurements. Initially the volume of carbon dioxide
      produced rose steadily to a constant value.

PMID- 11460320
TI  - An environmentally benign soybean derived fuel as a blending stock or replacement
      for home heating oil.
AB  - The use of bio-derived materials both as fuels and/or as blending stocks becomes
      more attractive as the price of middle distillate fuels, especially home heating
      oil, continues to rise. Historically, many biomass and agricultural derived
      materials have been suggested. One of the most difficult problems encountered
      with home heating oil is that of storage stability. High maintenance costs
      associated with home heating oil are, in large part, because of this stability
      problem. In the present research, Soygold, a soybean derived fuel, was added in
      concentrations of 10%-20% to both a stable middle distillate fuel and an unstable
      home heating oil. Fuel instability in this article will be further related to the
      organo-nitrogen compounds present. The soy-fuel mixtures proved stable, and the
      addition of the soy liquid enhanced both the combustion properties, and
      dramatically improved the stability of the unstable home heating oil.

PMID- 11460321
TI  - Adsorption and desorption of mercury by Bangpakong River sediments as influenced
      by salinities.
AB  - Mercury adsorption and desorption by Bangpakong River sediments (pH range 6.8
      7.8) of Thailand were investigated at salinity levels of 0, 5, 15 and 30@1000
      using a batch equilibration techniques. Using Freundlich isotherm adsorption and
      desorption data collected represented a nonlinear form. A significant portion (90
      99%) of added Hg (2-10 mg L-1) was sorbed by the sediment. Mercury adsorption
      isotherms or percentage adsorbed were similar among the four salinities tested.
      In the absence of salinity, Hg adsorption was highly influenced by pH. Whereas in
      the presence of salinity gradients, Hg(II)-organic complexes predominated over
      Hg(II)-Cl complexes, neutralizing effect of chloride concentrations and pH on the
      adsorption phenomena. Organic matter and clay contents of sediment were
      responsible for the Hg adsorption. Fe and Mn oxides showed negative correlation
      with the Hg adsorption capacity (r = -0.549 and -0.594 respectively). Increase in
      Hg desorbed from the sediments occurred only at the 30@1000 salinity level. The
      Hg adsorption-desorption characteristics of the sediments studied exhibited a
      very strong irreversible sorption of added inorganic Hg. River sediment such as
      sediment as shown in this study with significant levels of organic matter and
      clay have the potential to retain Hg making it less bioavailable and mobile thus
      reducing potential toxicity to aquatic organisms in the environment.

PMID- 11460322
TI  - A modeling study of water quality in main channel and estuarine wetland.
AB  - A simple computation framework is applied to include estuarine wetland and their
      interaction with main channels in estuarine modeling. The concept and the model
      implementation of the scheme are explained using a vertical two-dimensional model
      of estuarine hydrodynamics and water quality. The model was applied to the
      Tanshui River estuary and Kuan-Du wetland. The model is calibrated and verified
      by the available measured data. Simulations are also conducted for various
      upstream freshwater discharges to predict water quality in the main channel and
      estuarine wetland. The results show that the inclusion of estuarine wetland in a
      water-quality model not only provides a framework for computing water-quality
      conditions but also accounts for the interaction between wetland and main
      channel. The model provides a useful tool for environmental planning, protection
      and proposed wetland restoration works.

PMID- 11460323
TI  - Mercury distribution in sediment profiles of six Louisiana Lakes.
AB  - A study was conducted of six Louisiana Lakes to examine the relationship between
      sediment properties including mercury content and health advisories associated
      with mercury levels in fish. Comparison was made between three lakes with health
      advisories (Black Lake, Chicot Lake, and Henderson Lake) and three lakes where
      the levels of mercury in fish are below health advisory levels (False River, Lake
      St. John, and Miller Lake). Three sediment core samples were collected from each
      lake and sectioned into 2-cm increments to a depth of 20 cm. Sediment properties
      measured in each depth increment of the sediment profile included total mercury,
      137Cs activity (for sedimentation rate), and sediment organic matter content. Of
      the lakes studied, those lakes that have health advisories for mercury tended to
      have higher total mercury contents, usually higher sediment organic matter
      contents, and higher sedimentation rates than sediments in lakes where health
      advisories for mercury are not issued.

PMID- 11460324
TI  - Distribution characteristics of acid-dissolved trace metals of suspended
      particulate matter (SPM) in Kurashiki, Japan.
AB  - This study was undertaken to examine the distribution characteristics of such
      trace metals in fine particulate (especially with diameters of less than 2.1
      microns). The acid-dissolved metals in suspended particulate matter (0.1-9.0
      microns) were examined with consideration given to particle size over a 2-year
      period. It became clear the metals of artificial origin such as Pb, V, Cd, Ni, Cr
      exist in fine particulates (0.1 or more 2.0 microns), whereas metals of natural
      origin, such as Ti, Mn, Mg, and Sr primarily exist in coarse particles (2.1-9.0
      microns) in Kurashiki City, near the Mizushima Industrial Area in Japan.

PMID- 11460325
TI  - Experimental assessment of non-treated bentonite as the buffer material of a
      radioactive waste repository.
AB  - The bentonite-based material being evaluated in several countries as potential
      barriers and seals for a nuclear waste disposal system is of mostly sodium type,
      whereas most bentonite available in Korea is known to be of calcium type. In
      order to investigate whether local Korean bentonite could be useful as a buffer
      or sealing material in an HLW repository system, raw bentonites sampled from the
      south-east area of Korea were examined in terms of their physicochemical
      properties such as surface area, CEC, swelling rate, and distribution
      coefficient. The diffusion behavior of some radionuclides of interest in
      compacted bentonite was also investigated. Considering that HLW generates decay
      heat over a long time, the thermal effect on the physicochemical properties of
      bentonite was also included. Four local samples were identified as Ca-bentonite
      through XRD and chemical analysis. Of the measured values of surface area, CEC
      and swelling rate of the local samples, Sample-A was found to have the greatest
      properties as the most likely candidate barrier material. The distribution
      coefficients of Cs-137, Sr-85, Co-60 and Am-241 for Sample-A sample were measured
      by the batch method. Sorption equilibrium was reached in around 8 to 10 days, but
      that of Sr was found to be reached earlier. Comparing the results of this study
      with the reference data, domestic bentonite was found to have a relatively high
      sorption ability. For the effect of varying concentration on sorption, the values
      of Kd peaked at 10(-9)-10(-7) mol/l of radionuclide concentration. In XRD
      analysis, the (001) peak of Sample-A was fully collapsed above 200 degrees C. The
      shoulder appearing at about 150 degrees C in the DSC curve was found to be
      evidence that Sample-A is predominated by Ca-montmorillonite. The loss of
      swelling capacity and CEC of Sample-A started at about 100 degrees C. The
      swelling data and the (001) peak intensity of the heat-treated sample showed that
      they were linearly interrelated. The measured Kd values of Co-60, Cs-137 and Am
      241 for the samples heat-treated at various temperature showed that the domestic
      bentonite still retained sorption capacity below 100 degrees C. In addition to
      such findings of thermal effects, it was found that the presence of calcium in
      bentonite may help to assure long-term stability under the expected thermo-hydro
      conditions. The Da values of Sr-85, Cs-137, Co-60, Am-241 and Cl-36 were measured
      to be 1.073 x 10(1), 6.705 x 10(-1), 1.226 x 10(-1), 1.310 x 10(-2) and 9.490 x
      10(1) microns 2/sec, respectively, which could be arranged with the magnitude of
      their distribution coefficients, i.e. Cl > Sr > Cs > Co > Am. As the as-pressed
      density of bentonite increasing from 1.8 to 2.0 g/cm3, the Da-value of Cs-137
      decreased by 25%. From the analyses of the diffusion mechanism of radionuclides
      in compacted bentonite, the surface diffusion due to the concentration gradients
      of radionuclide sorbed on the bentonite particles was found to be a dominating
      transport process of radionuclides in compacted bentonite with 1.8 g/cm3. Bases
      on these results, it was identified that domestic bentonite has potential as a
      chemical barrier material in a repository system. Some data obtained in the
      results could contribute to the engineering parameters to design a waste package
      and engineered barrier or to develop an appropriate disposal concept satisfying
      the safety requirements.

PMID- 11460326
TI  - Adsorption of Rhodamine 6G from aqueous solutions on activated carbon.
AB  - The effects of particle size (0.5-1.0 mm), temperature (30-60 degrees C), and
      solution pH (7-9) on the adsorption equilibrium of dye Rhodamine 6G by activated
      carbon were studied in batch modes. The isotherm data could be well described by
      the Langmuir equation. Under the ranges tested, a maximum adsorption capacity of
      44.7 mg/g was obtained. Batch kinetic parameters such as the Lagergren's rate
      constant and intraparticle diffusion coefficient of adsorption were determined.
      It has been shown that the intraparticle diffusion of dye molecules within the
      adsorbents was identified as the rate-limiting step in the present adsorption
      process.

PMID- 11460327
TI  - Removal of fluoride ion from aqueous solution by a cerium-poly(hydroxamic acid)
      resin complex.
AB  - A cerium-loaded poly(hydroxamic acid) chelating ion exchanger was used for
      fluoride ion removal from aqueous solution. The resin was effective in decreasing
      the fluoride concentration from 5 mM down to 0.001 mM in acidic pH between 3 and
      6. The sorption followed a Langmuir model with a maximum capacity of 0.5 mmol/g.
      The removal is accomplished by an anion exchange mechanism. The rate constant for
      the sorption was found to be 9.6 x 10(-2) min-1. A column test shows that the
      fluoride ion was retained on the column until breakthrough point and the fluoride
      sorbed in the column can be eluted with 0.1 M NaOH. The column can be reused
      after being condition with hydrochloric acid at pH 4. The resin was tested and
      found to be effective for removal of fluoride from actual industrial wastewater.

PMID- 11460328
TI  - Separation, preconcentration, and determination of cadmium in drinking waters.
AB  - A fast method for separation, preconcentration and determination of cadmium in
      drinking (source, well, tap) and water for irrigation is described. Iron(III)
      hexamethylenedithiocarbamate, Fe(HMDTC)3, has the role of colloid precipitate
      flotation collector. The determination of cadmium in final water solutions
      preconcentrated by flotation can be performed by flame (FAAS) or electrothermal
      atomic absorption spectrometry (ETAAS). The method applied, either FAAS or ETAAS,
      depends of the concentration level of analyte in the water sample investigating.
      The AAS results are compared with inductively coupled plasma-atomic emission
      spectrometric measurements (ICP-AES) as an independent method. The ETAAS
      detection limit of cadmium is 0.002 microgram/L.

PMID- 11460329
TI  - Adsorptive characteristics of cadmium and lead on the goethite-coated sand
      surface.
AB  - This study was conducted to develop a heating process for coating crystalline
      goethite on the sand surface to utilize the adsorbent properties of the coating.
      Goethite-coated sand was investigated for adsorbing cadmium and lead ions from
      water by batch and column experiments. Chemical analysis (energy dispersive
      analysis of X-ray, EDAX) was used for characterizing the cadmium and lead
      adsorption sites on goethite-coated sand. From the results of the batch
      experiments, the cadmium and lead ions could be adsorbed effectively on the
      goethite-coated sand. Maximum adsorption capacity values for cadmium and lead
      were 319, 704 micrograms-Cd/g-sand and 702, 1241 micrograms-Pb/g-sand at pH =
      5.0, pH = 6.0, respectively. The interaction between cadmium, lead ions and
      goethite on sand surface was primarily to cause the chemical bonding. Results
      from column experiments indicated that the cadmium and lead ions could be removed
      higher than 95% before 110, 130 and 66, 85 numbers of pore volume of influent
      were treated at pH = 5.0 and pH = 6.0, respectively.

PMID- 11460330
TI  - Concentrations of heavy metals in roadside soils, plants, and landsnails from the
      West Bank, Palestine.
AB  - Concentrations of Cu, Cd, Pb and Zn were determined in roadside soil, plant and
      landsnail samples along Nablus-Ramallah main road in the West Bank. Average
      concentrations (microgram.g-1, dry weight) of the four metals in soil samples
      were, Cu: 23.8, Zn: 128.3, Cd: 0.45 and Pb: 149.9. These values were higher than
      those found in soil samples collected from control sites. Metals in roadside
      plant samples were within normal levels although plants from control sites were
      found to have slightly less metals. Different parts of a plant (roots, stem &
      leaves) were found to accumulate metals in different concentrations. The average
      concentration (microgram.g-1) of metals in different plant parts were: Cu: < 5.2,
      Cd: < 1.0, Pb: < 2.19 and Zn: < 5.18. Average concentrations (microgram.g-1) of
      metals in the three roadside snails were ranging between 121-132 for Cu, 18-27
      for Cd, 21-24 for Pb and 43-69 for Zn. Snails were found to magnify Cd to serious
      levels (> 30-50 times higher than in plants and soils). Lead in snails was about
      10 times higher than that in plant leaves and much less than that in roadside
      soils. Other metals in snails did not show abnormal concentrations.

PMID- 11460331
TI  - Bioaugmentation and anaerobic treatment of pharmaceutical effluent in fluidized
      bed reactor.
AB  - The start-up of an anaerobic fluidized bed reactor was carried out using a single
      inoculum (supernatant of anaerobic digester) and later on with multiple inoculum
      (a mixture of supernatant of anaerobic digester and volatile fatty acid (VFA)) to
      achieve a faster start-up. Then regular experiments were carried out to study the
      effect of hydraulic retention time (HRT) on COD removal (%) and biogas
      production. The pharmaceutical effluent with COD of 2000 to 4000 mg/L was treated
      in a fluidized bed reactor using an enricher-reactor concept with a hydraulic
      retention times of 3 (Uf = 6 Umf) to 24 (Uf = 1.5 Umf) hr. The maximum COD
      removal (%) of 91.2 and a maximum biogas production of 5.62 L/d were obtained at
      24 hr HRT for a maximum COD concentration of 4000 mg/L corresponding to a
      fluidization velocity (Uf) of 20 m/hr (1.5 Umf) using a granular activated carbon
      bed of average size 700 microns.

PMID- 11460332
TI  - Bioleaching of metals from anaerobic sewage sludge: effects of total solids,
      leaching microorganisms, and energy source.
AB  - The effects of municipal sewage sludge solids concentration, leaching
      microorganisms (Thiobacillus thiooxidans or Thiobacillus ferrooxidans) and the
      addition of energy source (S0 or Fe(II)) on the bioleaching of metals from sewage
      sludge has been investigated under laboratory conditions using shake flasks. The
      results show that metal solubilization was better accomplished if additional
      energy source is supplemented to the microorganisms and that T. thiooxidans
      furnishes, in general, more adequate conditions for the bioleaching than T.
      ferrooxidans. At a total solids concentration of 70 g L-1 (originally present in
      the sludge) pH drop and ORP increase are attenuated, so metal solubilization is
      negatively affected. It was also demonstrated that if lead (Pb) solubilization is
      to be achieved, than a special combination of microorganism/energy source must be
      applied.

PMID- 11460333
TI  - Feasibility study of treated sewage irrigation on paddy rice culture.
AB  - A feasibility study was performed to examine the agronomic application of the
      treated sewage on paddy rice culture through field experiment. The domestic
      sewage was treated using a constructed wetland system, a subsurface flow type
      consisting of sand and macrophyte. The effluent of the wetland system was diluted
      to maintain the total nitrogen concentration below 25 mg/L and was used as
      irrigation water. Addition of the treated sewage to the irrigation water showed
      no adverse effect on the paddy rice culture; in fact some enhancement was noticed
      in both growth and yield. Irrigation with the treated sewage after the
      concentration was adjusted accompanied by conventional fertilization showed a
      better result, with the yield exceeding that of the control where clean water was
      used, thus suggesting that reuse of the treated sewage as supplemental irrigation
      water could be a feasible and practical alternative. For a full-scale
      application, however, further study is recommended on the specific guideline for
      controlling the major water quality components in the treated sewage.

PMID- 11460334
TI  - Domestic wastewater treatment using immobilized sludge fluidized-bed reactors.
AB  - Bench-scale fluidized-bed reactors using the immobilized activated sludge process
      were studied for the treatment of domestic wastewater. Different intermittent
      aeration patterns were investigated in order to improve the total nitrogen (TN)
      removal. The best TN removal at 74.4% was achieved at an HRT of 6 hours (with
      corresponding BOD loading rate of 0.766 kg/m3/d) and an aeration-pattern of 1,3
      (the hours of aeration and non-aeration time cycle). The removal efficiencies for
      organic carbon, NH4(+)-N, TKN and TSS were not affected and remained at more than
      90%. Simultaneous organic carbon and nitrogen removal was accomplished in a
      single immobilized sludge reactor. The impact of various influent feed patterns
      on the treatment was examined. The continuous feed pattern was recommended as it
      ensured good TN removal without any adverse impacts on the removal of organic
      carbon, NH4(+)-N, TKN and TSS. The immobilized sludge beads exhibited
      satisfactory mechanical stability without apparent breakage over the 180-day
      experiment period.

PMID- 11460335
TI  - Formation of heavy metal species during PVC-containing simulated MSW
      incineration.
AB  - The effect of PVC-derived chlorine on heavy metal emissions in MSW incineration
      was investigated using a tubular furnace and simulated MSW spiked with PVCs and
      heavy metals (Cd, Cr, Cu, and Zn). The molar ratio of the chlorine content to
      that of the heavy metal (Cl/M ratio) was varied from 3-200 as one parameter. The
      results indicated that the major species found in the fly ash were chlorides of
      alkaline and alkali-earth metals, whereas those identified in the bottom ash were
      MgSiO3, SiO2 and some complex aluminates and silicates. The emission of heavy
      metals and/or their compounds, with extreme and medium volatility, tended to be
      enhanced within the lower Cl/M range, whereas those with a refractory volatility
      were likely to be affected within the higher Cl/M range. However, those with an
      extremely refractory volatility were less affected by an increase of the Cl/M
      ratio. The variation of speciation and partitioning in MSW combustion as affected
      by the Cl/M ratio are discussed.

PMID- 11460336
TI  - The emission characteristics of a small D.I. diesel engine using biodiesel
      blended fuels.
AB  - Biodiesel and biodiesel blends provide low emissions without modification on the
      fuel system of conventional diesel engines. This study aims to develop a new
      domestic biodiesel production procedure which makes use of waste fryer vegetable
      oil by transesterification method, and further investigates the emission
      characteristics of a small D.I. diesel engine using biodiesel blends and diesel
      fuels, respectively. The 20/80 and 30/70 blends of biodiesel to diesel fuel are
      used in this study. The emission characteristics include smoke emissions, gaseous
      emissions (CO, HC, NOx and SO2), particle size distributions and number
      concentrations at a variety of steady state engine speed points. We have found
      that diesel engine fueled with biodiesel blends emits more PM2 particle number
      concentrations than those with diesel fuel, and PM2 number concentration
      increases as biodiesel concentration increases. As for the smoke and gaseous
      emissions, such as CO, HC, NOx and SO2, the results favored biodiesel blends.

PMID- 11460337
TI  - Non-combustible waste vitrification with plasma torch melter.
AB  - Non-combustible radioactive wastes generated from Nuclear Power Plants (NPPs) are
      composed of concrete, glass, asbestos, metal, sand, soil, spent filters, etc. The
      melting tests for concrete, glass, sand, and spent filters were carried out using
      a 60 kW plasma torch system. The surrogate wastes were prepared for the tests.
      Non-radioactive Co and Cs were added to the surrogates in order to simulate the
      radioactive waste. Several kinds of surrogate prepared by their own mixture or by
      single waste were melted with the plasma torch system to produce glassy waste
      forms. The characteristics of glassy waste forms were examined for the volume
      reduction factor (VRF) and the leach rate. The VRFs were estimated through the
      density measurement of the surrogates and the glassy waste forms, and were turned
      out to be 1.2-2.4. The EPA (Environmental Protection Agency) Toxicity
      Characteristic Leaching Procedure (TCLP) was used to determine the leach
      resistance for As, Ba, Hg, Pb, Cd, Cr, Se, Co, and Cs. The leaching index was
      calculated using the total content of each element in both the waste forms and
      the leachant. The TCLP tests resulted in that the leach rates for all elements
      except Co and Cs were lower than those of the Universal Treatment Standard (UTS)
      limits. There were no UTS limits for Co and Cs, and their leach rate & index from
      the experiments were resulted in around 10 times higher than those of other
      elements.

PMID- 11460338
TI  - Removal of heavy metals from sewage sludge by acid treatment.
AB  - Sludge samples were found to contain significant amounts of heavy metals (Cr, Cu,
      Ni, Pb and Zn) and were subjected to acid treatment using either hydrochloric,
      sulfuric, nitric or phosphoric acid. The optimum combination, in terms of metal
      removal efficiency and environmental impacts was sought through a variety of
      tests by applying a ratio of 1:5 of sludge quantity (g) per volume of acid (ml).
      The concentrations of the different acids used, were in the range of 5%-20% and
      the contact times ranged between 15 and 60 minutes. The optimum combination was
      achieved when the sludge samples were in contact with H2SO4 20% v/v for 60
      minutes. In order to estimate the metal leachability, the heavy metal content as
      well as the metal distribution in the residue were investigated and it was found
      that most of the heavy metal content was extracted while the remaining was
      removed from the initial mobile phases to the more stable ones.

PMID- 11460339
TI  - [Concept and diagnostic standard for chronic obstructive pulmonary diseases].

PMID- 11460340
TI  - [Epidemiology and risk factors for COPD].

PMID- 11460341
TI  - [Clinical symptoms and physical findings in patients with COPD].

PMID- 11460343
TI  - [Imaging diagnosis of COPD].

PMID- 11460342
TI  - [Pulmonary functions associated with COPD].

PMID- 11460344
TI  - [Airway inflammation in COPD].

PMID- 11460345
TI  - [Pulmonary circulatory disturbance in COPD].

PMID- 11460346
TI  - [Pathology of COPD].

PMID- 11460347
TI  - [Exercise tolerance in COPD].

PMID- 11460348
TI  - [Drug therapy of COPD].

PMID- 11460350
TI  - [Physical therapy of COPD].

PMID- 11460349
TI  - [Long-term oxygen inhalation therapy of COPD].

PMID- 11460351
TI  - [Energy metabolism and nutritional management of patients with COPD].

PMID- 11460352
TI  - [Management of acute exacerbation of COPD].

PMID- 11460353
TI  - [Lung volume reduction surgery in pulmonary emphysema].

PMID- 11460354
TI  - [Diagnosis and treatment of COPD: discussion].

PMID- 11460355
TI  - [Neurosarcoidosis presenting overt myopathy].

PMID- 11460356
TI  - [Interstitial nephritis after treatment with mesalazine in the patient with
      ulcerative colitis].

PMID- 11460357
TI  - [Stent implantation in a case of myocardial bridging with resistant angina
      pectoris].

PMID- 11460358
TI  - [Rapidly progressive and fatal multiple organ failure and necrosis of lower
      extremities due to Vibrio vulnificus sepsis].

PMID- 11460359
TI  - [Oral administration of beraprost sodium did not exacerbate pulmonary
      hypertension with CREST syndrome].

PMID- 11460360
TI  - [Systemic lupus erythematosus with anti-phospholipid syndrome complicated with
      polyneuropathy].

PMID- 11460361
TI  - [Gene therapy of chronic rheumatoid arthritis].

PMID- 11460362
TI  - [Vibrio septicemia].

PMID- 11460363
TI  - [Behavior therapy for obesity].

PMID- 11460364
TI  - [Therapeutic outline for gastric lymphoma].

PMID- 11460365
TI  - [Therapeutic policy for malignant lymphoma of the aged].

PMID- 11460366
TI  - [Malignant lymphoma developing with a background of inflammatory conditions].

PMID- 11460367
TI  - [Lymphoma that is difficult to be differentiated from inflammatory diseases].

PMID- 11460368
TI  - [Adult T-cell leukemia].

PMID- 11460369
TI  - [Opportunistic lymphoma].

PMID- 11460370
TI  - [Malignant lymphoma: progress in therapeutics and cooperation between physicians
      and medical facilities. Discussion].

PMID- 11460371
TI  - [Successful cyclosporine therapy for a young patient with refractory anemia,
      myelodysplastic syndrome].

PMID- 11460372
TI  - [Hypophosphatemic rickets with normoalkaliphosphatemia, ossification of the
      posterior longitudinal ligament and yellow ligament].

PMID- 11460373
TI  - [Multiple organ tuberculosis disclosed by epididymal lesion].

PMID- 11460374
TI  - [Listeriosis in an adult patient with diabetes mellitus].

PMID- 11460375
TI  - [Renovascular hypertension coexisting with an aldosteronoma].

PMID- 11460376
TI  - [Acquired haemophilia A caused by inhibitor against factor VIII].

PMID- 11460377
TI  - [Ultrasonic diagnosis of cerebral apoplexy].

PMID- 11460378
TI  - [Chronic rheumatoid arthritis and the involvement of the nervous, endocrine, and
      immune systems].

PMID- 11460379
TI  - [Treatment of B cell lymphoma by using monoclonal antibodies].

PMID- 11460380
TI  - [Progress in the treatment of malignant lymphoma].

PMID- 11460381
TI  - [New WHO classification of malignant lymphoma].

PMID- 11460382
TI  - [Pathological diagnosis of malignant lymphoma].

PMID- 11460383
TI  - [Methods for histological diagnosis of malignant lymphoma].

PMID- 11460384
TI  - [Progress and indication for immunohistological examinations of malignant
      lymphoma].

PMID- 11460385
TI  - [Genomic aberrations in malignant lymphoma].

PMID- 11460386
TI  - [Latest findings on Hodgkin's disease].

PMID- 11460387
TI  - [Diagnostic sequence for malignant lymphoma].

PMID- 11460388
TI  - [Prognostic factor and models for prognosis of malignant lymphoma].

PMID- 11460389
TI  - [Clinicopathological classification of malignant lymphoma].

PMID- 11460390
TI  - [Standard treatment of malignant lymphoma (Hodgkin's and non-Hodgkin's
      lymphoma)].

PMID- 11460391
TI  - [New therapy for severe osteoporosis. Bone development with parathyroid hormone?
      (interview by Brigitte Moreano)].

PMID- 11460392
TI  - [Milestone studies provide evidence: sartans have a nephroprotective effect.
      Evidence is clear].

PMID- 11460393
TI  - [New guidelines in hypertension. What is relevant for general practice?].
AB  - The latest guidelines aim to help improve the diagnosis and treatment of
      hypertension. This purpose is served by the following recommendations: Blood
      pressure values of 140/90 must already be considered to signal hypertension.
      Normotension in turn, is subdivided into optimal, normal and high-normal blood
      pressure. This is relevant in particular to certain high risk groups, for whom an
      appreciable lowering of blood pressure is associated with a further decrease in
      mortality. Particular attention is warranted in isolated systolic hypertension,
      which represents a cardiovascular risk that should not be underestimated. Every
      hypertensive should undergo a basic examination during which pointers to
      secondary hypertension must be investigated. Evidence-based, non-medication
      measures include weight reduction, salt restriction, reduction of alcohol use,
      and regular "endurance" exercise. The selection of antihypertensive drugs should
      be determined by concomitant diseases. All in all, the therapeutic strategy will
      be increasingly be oriented to such additional risk factors as diabetes mellitus,
      dyslipidemia or already present organic damage.

PMID- 11460394
TI  - [Calcium antagonists in treatment of hypertension. Proper selection and drug
      combinations if needed].

PMID- 11460395
TI  - [Alpha-blockers in therapy of arterial hypertension. No longer the drug of first
      choice].

PMID- 11460396
TI  - [AT1 receptor antagonists as single drug in hypertension? It's too early for
      that!].

PMID- 11460397
TI  - [New guidelines from the viewpoint of the general practitioner. Where is patient
      education?].

PMID- 11460398
TI  - [Emergencies in general practice, 17. Lack of hyperglycemic control in diabetes
      mellitus].

PMID- 11460399
TI  - [New guidelines for sensible therapy. Gallstones in the ultrasound? Exercise
      patience!].

PMID- 11460400
TI  - [Therapeutic compliance in asthma patients? Some blow their spray simply into the
      wind...].

PMID- 11460401
TI  - [Pain therapy instead of antibiotics].

PMID- 11460402
TI  - [Patient with pallor, fatigue, weight loss. LDH values need explanation].

PMID- 11460403
TI  - [Pathological stress ECG without stenocardia. Wolff-Parkinson-White syndrome].

PMID- 11460404
TI  - [Electronic prescription--the first step to total networking. Soon your practice
      will be a "big brother container"].

PMID- 11460405
TI  - [Controlling herpes zoster. End end to bullae].

PMID- 11460406
TI  - [Comparison of triptans. Migraine patients have a choice].

PMID- 11460407
TI  - [CSE inhibitors after coronary event. How soon administered?].

PMID- 11460408
TI  - [Treatment of osteoporosis. Compliance is significantly enhanced].

PMID- 11460409
TI  - [Antihypertensive therapy. Can a calcium antagonist stop arteriosclerosis?].

PMID- 11460410
TI  - [Evaluation of chronic cough. 4 steps lead to success].

PMID- 11460411
TI  - [Breast cancer screening. In search of more quality].

PMID- 11460412
TI  - [Alcohol drinking at the threshold of abuse. When is it really critical?].
AB  - The risk of developing a given alcohol-related illness must be considered on an
      individual basis. In patients with mood and anxiety disorders even moderate
      amounts of alcohol may lead to psychiatric problems. Comorbid alcohol-related
      disorders are found to be accumulated in patients with personality disturbances
      and in those with bipolar affective disorders. The reported favorable effects of
      moderate consumption of alcohol apply only when cardiovascular risks are present
      in the absence of other health risks that are aggravated by alcohol use. The
      concept of the "hazardous use of alcohol" is contained in the current issue of
      ICD-10. The transition to alcohol-induced disorders is characterized by the
      criteria for intoxication, injurious use and the dependency syndrome. A need for
      treatment or preventive measures may, however, be given even when these criteria
      have not (yet) been met.

PMID- 11460413
TI  - [Forgetfulness and light cognitive impairment. What can the physician still
      tolerate?].
AB  - Forgetfulness is defined as a subjectively bothersome impairment of the ability
      to recall facts that are unequivocally known to be stored in the memory.
      Objectifiable memory deficits may accompany numerous physical and neurological
      illnesses, but may also be seen in depressive states. Below average-for-age
      cognitive performances that do not reach the level of dementia are referred to as
      mild cognitive impairment, which in some cases represents a pre-dementia stage of
      Alzheimer's disease. Its recognition and differentiation from age-related
      performance deficits is now possible using simple, but sensitive
      neuropsychological tests. An important aim of the diagnostic work-up is the
      recognition of potentially reversible causes. For this purpose, physical
      examination and laboratory investigations are helpful. Structural and functional
      imaging procedures can provide information about cerebral causes. Biochemical
      indicators of neurogenerative processes are currently being developed. Cognitive
      training measures possibly have only a small and temporary effect. In patients
      with mild cognitive impairment, nootropic agents apparently have a symptomatic
      effect. Whether antidementia agents are capable of stopping the progress of mild
      cognitive impairment to full-blown dementia is currently being investigated in
      ongoing trials.

PMID- 11460414
TI  - [Secondary hypertension, 2: Renal failure. The kidney is the victim and
      perpetrator].

PMID- 11460415
TI  - [Problems with the stoma. How you can advise your patients].
AB  - Stoma management is associated with various problems, depending on the type and
      location of the stoma and on the individual situation. Besides such general
      problems as smell, flatulence and local skin problems, typical surgical
      complications such as retraction and stenosis, prolaps and peristomal hernia are
      of major relevance. Many of these problems can be avoided by careful placement of
      the stoma and a meticulous surgical technique. Where indicated, the surgical
      correction of a problem is usually not very difficult, and is most helpful for
      the patient.

PMID- 11460416
TI  - [Therapy of arthrosis. Life threatening gastrointestinal events can be reduced].

PMID- 11460417
TI  - [Results of the VIGOR study. Rofecoxib halves the complication rate].

PMID- 11460418
TI  - [Coronary heart disease in the woman. About a not insignificant difference].

PMID- 11460419
TI  - [Optimized therapy. Greater rate of effectiveness with consensus interferon].

PMID- 11460420
TI  - [Consensus interferon. Problematic patients are not a problem].

PMID- 11460421
TI  - [10 DM fee for an occult blood test. That would drastically reduce the incidence
      of colon carcinoma].

PMID- 11460422
TI  - [Steroids in Crohn disease. Side-effects can be minimized].

PMID- 11460423
TI  - [Hypertensive diabetic patients. Plus points for selective beta 1-blockade].

PMID- 11460424
TI  - [Oral enzyme therapy in osteoarthritis of the knee. Proteolytic enzyme are
      effective with few risks].

PMID- 11460425
TI  - [Chronic bronchitis. Gold standard from the internet].

PMID- 11460426
TI  - [The taboo topic of sexual activity in hypertensive patients. Pioneer study from
      Pavia proves: potency is not impaired].

PMID- 11460427
TI  - [The husband: a coronary risk factor].

PMID- 11460428
TI  - [Revolution in spinal surgery. What is the value of intervertebral disk
      prostheses? (interview by Waldtraut Paukstadt)].

PMID- 11460429
TI  - [19. Constipation--etiology, diagnosis and therapy].

PMID- 11460430
TI  - The return of natural ventilation.

PMID- 11460431
TI  - Cellular divide.

PMID- 11460432
TI  - Battle for Bush's soul.

PMID- 11460433
TI  - A question of life or death.

PMID- 11460434
TI  - The telltale heart (test).

PMID- 11460435
TI  - Dialing & driving don't mix.

PMID- 11460436
TI  - Changing directions. Nashville's behavioral healthcare getting into acute-care
      hospital industry.

PMID- 11460437
TI  - It's a deal. Calif. attorney general approves Sutter Health's takeover of St.
      Luke's.

PMID- 11460438
TI  - Match made in court. For-profit chain agrees to buy not-for-profit hospital after
      bankruptcy filing.

PMID- 11460439
TI  - Fighting to be. AMA's 'unity' project struggles against indifference.

PMID- 11460440
TI  - The ties that rend. OB/GYN group ends 71-year relationship with AMA.

PMID- 11460441
TI  - Some online savings seen. Study projects $6 billion in eventual annual cost
      reductions for supply chain.

PMID- 11460442
TI  - Revenue stopper. Bungled billing system conversions are plaguing the hospital
      industry.

PMID- 11460443
TI  - Good news on fraud, dumping sparks concern. GAO reports find most providers don't
      set out to defraud Medicare, Medicaid.

PMID- 11460444
TI  - Follow the winners. Top 100 cardiovascular hospitals cut mortality rates as well
      as costs, study finds.

PMID- 11460445
TI  - Spotlight on revenue. HFMA survey shows billing, collections professionals lead
      the pack for pay increases.

PMID- 11460446
TI  - Labor flexes muscle. United American Nurses votes to join AFL-CIO, sends message
      to bosses.

PMID- 11460447
TI  - Meet the Veep's new aide.

PMID- 11460448
TI  - The real price of fighting AIDS.

PMID- 11460449
TI  - Failing grade for breast exams?

PMID- 11460450
TI  - [Computer-assisted surgical planning].

PMID- 11460451
TI  - [Computer-assisted surgical planning. 3-D software for the PC].
AB  - A potent software was developed for virtual planning in orthopedic surgery with
      complex spatial relationships, that runs on a standard PC with Windows
      98/NT/2000. This voxel-based 3D-software creates data from tomographic images
      (CT, MRI, 3D-Sono, PET) in Dicom-III-format, that are visualized in near real
      time as 2D-reconstructions or 3D-images. For three-dimensional analysis
      interactive tools, geometric rulers and an anatomic coordinate-system are
      available. Multiplanar osteotomies are carried out with a virtual saw. Selected
      segments are moved freely to mimic fracture reduction and deformity correction.
      Three-dimensional movement coordination is supported by problem-oriented movement
      features and a 3D-mouse. User defined objects in CAD-format like implants or
      anatomical templates can be inserted and moved. Matching of two volume data sets
      is possible as well as simultaneous processing of different data sets. All 3D
      reconstructions can be calculated as virtual radiographs and viewed
      stereoscopically with LCD-shutter glasses. Export features in various data
      formats allow further processing of all volume data in CAD applications and rapid
      prototyping. An intra-operative navigation system can be integrated via an
      interface. This universally applicable software allows thorough three-dimensional
      analysis and processing of volume data sets from tomographic images and can be
      used in various applications through its flexible modular setup.

PMID- 11460452
TI  - [Outcome analysis after open reconstruction of rotator cuff ruptures. A
      comparative assessment of recent evaluation procedures].
AB  - Outcome evaluation is becoming increasingly important for reconstructive surgery
      in musculoskeletal diseases. In addition to established shoulder-scores, new
      outcome-scores are being developed to cover all effects caused by a disease or
      intervention. Three validated, self-administered shoulder questionnaires were
      applied prospectively in 23 otherwise healthy patients suffering from rotator
      cuff deficiency. These were correlated to the Constant-Murley Shoulder Score and
      to a visual analogue scale for satisfaction. 7 women and 16 men with combined
      tears of supraspinatus and infraspinatus (mean age 55.3 +/- 10.5, r/l: 14/9, FU
      57.8 +/- 15.7 weeks) were gathered prospectively and evaluated pre- and
      postoperatively with the American Shoulder and Elbow Surgeons Shoulder Index
      (ASES), the Simple Shoulder Test (SST) and the Disabilities of the Arm, Shoulder
      and Hand Module (DASH questionnaire). In addition, a visual analogue scale for
      satisfaction was employed. All four scores as well as the visual analogue scale
      revealed improvement at a statistically significant level (paired, two-tailed t
      test, P < 0.01) after surgery. All questionnaires had a significant correlation
      with the Constant-Murley Shoulder Score (Pearson's correlation coefficient: ASES:
      r = 0.871, P < 0.01; DASH: r = -0.758, P = < 0.01; SST: r = 0.494, P < 0.05). All
      were easy to apply and provided a reliable, postoperative evaluation of shoulder
      function. The SST was easy to apply, however compound outcome analysis was only
      possible with the ASES Shoulder Index and the DASH questionnaire. The DASH scale
      was the most complex evaluation instrument. The Constant-Murley Shoulder Score
      comprises a physical examination which is advantageous but must be carried out in
      the clinic. For postoperative assessment, without the patient having to return to
      the clinic, the ASES Shoulder Index is preferred as it correlates well with the
      Constant-Murley Shoulder Score (r = 0.871) and the visual analogue scale for
      satisfaction (r = 0.762).

PMID- 11460453
TI  - [Development and validation of the Visual Analogue Scale (VAS) Spine Score].
AB  - The aim of the study was the development and validation of a new subjective
      rating scale for assessment of outcome in patients with thoracolumbar fractures
      and fracture dislocations. The VAS spine score consists of 19 score items, using
      100-mm visual analogue scales. The items are answered by the patients
      independently of rater assessment. To measure the analogue scales and calculate
      the score, a computer-aided system was evolved consisting of self-developed
      software and digitizer board. The overall score is the mean of all items answered
      with values between 0 and 100. The individual score loss is calculated as the
      difference between the preinjury score and at follow-up with values between 0 and
      100. The VAS spine score was tested for reliability with a group of 136 healthy
      volunteers. We performed a test-retest study with an interval of 24 h. For
      statistical analysis of the validity, we prospectively followed a group of 53
      patients with the new outcome score. We chose patients with injuries of the
      thoracolumbar spine, all having been operatively treated by combined posterior
      anterior stabilization and fusion between 1994 and 1996. In the reference group,
      the average test score was 91.95 (58-100) and 92.10 (58-100) at retest. The mean
      individual difference between test and retest scored 1.037 (0-8). A high
      reliability was proved by a strong correlation with a coefficient of 0.976 (p <
      0.001). A high internal consistency of the VAS spine score was shown by a
      Cronbach-alpha of 0.9117. The mean score for the preinjury status of the patients
      was comparable to the reference group, amounting to 89.60 (21-100). The mean
      score at the time of implant removal was significantly (p < 0.001) decreased to
      58.25 (13-97). Until the time of follow-up a significant (p < 0.001) increase was
      noted, and the group scored 66.08 (15-100) at follow-up. This was a significant
      (p < 0.001) difference compared with the preinjury status. The individual score
      loss averaged 24.1 (0-80). In the patient group we also noted a Cronbach-alpha >
      0.95, indicating a high internal consistency. With the VAS spine score the
      authors have inaugurated a new tool for outcome measurement in the treatment of
      patients with thoracolumbar injuries. The study has proved the score to be both
      reliable and valid. The application of the score is helpful in analyzing the
      subjective outcome, and the results can be correlated with objective measures.
      The score is a useful tool for comparative clinical studies, addressing the
      outcome after different methods of treatment.

PMID- 11460454
TI  - [Bone segment transport of the femur. Biomechanical value of an unreamed titanium
      intramedullary nail with reference to stiffness of external distraction systems].
AB  - The influence of an unreamed femur nail on axial and torque stiffness of nine
      different external fixator devices was investigated in a biomechanical study.
      With a newly developed femur bone model simulating segmental transport, 582
      biomechanical tests were performed. The additional use of an unreamed femur nail
      (UFN) increased axial stiffness of the external fixator devices up to 8108%
      (average 1673.8-2631.8%) and increased torque stiffness up to 86% (average 47%).
      The best results could be achieved when combining a small-diameter UFN (9 x 360
      mm, Synthes Co.) and external fixator devices with high torque and comparatively
      little axial stiffness. The use of stainless steel half-pins instead of titanium
      half-pins improved torque stiffness significantly. Concerning the biomechanical
      demands made on external fixator devices used for femoral segmental transport,
      the Hexfix fixator with steel bar and steel half-pins combined with an UFN
      achieved the best results.

PMID- 11460455
TI  - [Meniscus refixation: suture or anchor?].
AB  - Suture techniques are the standard for fixation of meniscus bucket-handle
      lesions. In 1993 a new method for meniscus repair with self-reinforced
      biodegradable "arrows" was introduced. Currently, various meniscus implants are
      available in Germany and are widely used clinically. The purpose of this paper
      was to evaluate and discuss the literature on biodegradable meniscus implants.
      Relevant articles were retrieved from Medline of the National Library of Medicine
      (1966 until July 2000) using the combined search strategy for the keywords
      "meniscal repair" and "arrow." Ten publications were found. The reported
      advantages of meniscus arrows are the reduced operation time, the easy surgical
      technique, and the reduced risk of neurovascular injury. In most experimental
      studies, lower failure strength of meniscus arrows was found compared to meniscus
      sutures. In clinical studies, the meniscal healing rates comparing the arrow
      technique and suture technique are comparable. Various complications of the new
      arrow technique have been reported such as inflammatory foreign-body reaction,
      cartilage lesions, and arrow displacement. Based on the existing literature, no
      final judgment is possible. Currently, individual indications depending on the
      kind of meniscal lesion and location are recommended. A combination of suture and
      arrow technique might be a treatment option, but further prospective randomized
      studies and longer follow-ups are necessary.

PMID- 11460456
TI  - [Is prolonged ambulatory physical therapy after anterior cruciate ligament-plasty
      indicated? Comparison of costs and benefits].
AB  - Thirty-five patients were prospectively examined on average 5.9 and 11.1 months
      after reconstruction of the anterior cruciate ligament. Eighteen patients were
      treated postoperatively with a regular physiotherapy (PT) program 2-3 times per
      week for 30 min, 17 patients with a special, extended, and supervised
      rehabilitation program 3-5 times per week for 2.5 h. Criteria for exclusion from
      this study were previous operation or fractures of the affected knee. The bases
      for the evaluation of the clinical results were the clinical examination, the
      Lysholm and Tegner scores, KT 1000, angular reproducibility according to Barrett
      (proprioception), and the figure-of-eight hop test. It appeared that patients
      treated with extended ambulatory physiotherapy (EAP) gained a significantly
      higher degree of functionality in the Lysholm score after 5.9 months (p < 0.02)
      and the Tegner score after 11.1 months (p < 0.05) than patients treated with
      regular physiotherapy. Patients treated with EAP also displayed better results in
      the proprioceptive capability test with an angular deviation of 5.8 degrees after
      5.9 months compared to 11 degrees in patients receiving regular PT. After 11.1
      months, there were no differences in proprioceptive capability between the two
      groups. Although the EAP patients were faster in the figure-of-eight hop test
      (0.39 s difference compared to 0.58 s in the PT patients), the results were not
      statistically significant. In KT 1000 ventral tibial instability was on average
      21% lower in the PT patients than in the EAP patients. After 11.1 months, both
      groups exhibited the same median value of 3 mm. Furthermore, EAP patients were
      able to return to work after 36.7 days on average, a 35% shorter period than in
      the case of PT patients (55 days), also of statistical significance (p < 0.02).
      To conclude, the primarily higher costs of this intensive rehabilitation program
      are justified by the better functional outcome linked with an earlier return to
      work.

PMID- 11460457
TI  - [Preoperative computerized tomography diagnosis of fractures of the tibial
      plateau].
AB  - Within the last decade computed tomography has become an important instrument for
      skeletal diagnosis. In this study the value of helical CT-scan was compared with
      plan X-rays and conventional tomography in 45 patients having sustained an
      intraarticular tibia plateau fracture. Between plan roentgenogramms and CT-scan
      the fracture classification according to the AO-classification was changed in 40%
      of all patients, in 39 cases the amount of impression or dislocation increased
      with a mean of 4.2 mm. Especially tiny fragments were better visible and
      therefore responsible for the shift of many B1 fractures to group B3. The
      difference between conventional tomography and computed tomography was less
      impressive, a change of fracture classification could be observed in only 6.7% of
      all cases.

PMID- 11460458
TI  - [Value of magnetic resonance tomography (MRI) in diagnosis of triplane fractures
      of the distal tibia].
AB  - The rare transitional fractures occur in adolescents at a time of incomplete
      dosis of the epiphysis. The anatomy of this fracture type is complex with the
      fracture line running in multiple planes. Conventional plain film radiographs
      often underestimate the extent and geometry of the fracture due to its transverse
      components. This study was performed to asses the benefit of MR-imaging compared
      to plain film radiographs in diagnosis and analysis regarding fracture-type,
      anatomy and dislocation of fracture. During a time period of 18 months we treated
      15 patients with a fracture of the distal tibial epiphysis. In addition to plain
      film radiographs they got MRI of the distal tibia. Plain film radiographs and MRI
      were anonymized and diagnosed by 2 surgeons and 2 radiologists. 12 transitional
      fractures were diagnosed in plain radiographs as well as MRI, but regarding our
      criteria as above, we found two wrong classifications of fracture-type, an
      underestimation of fracture dislocation of an average of 0.5 mm in plain film
      radiographs and two rotational dislocations were missed. The MRI was found to
      provide anatomical detail and information superior to plain film radiographs.

PMID- 11460459
TI  - [LISS tractor. Combination of the "less invasive stabilization system" (LISS)
      with the AO distractor for distal femur and proximal tibial fractures].
AB  - Minimally invasive plate osteosynthesis (MIPO) in conjunction with the less
      invasive stabilization system (LISS) first requires reduction and retention of
      the fracture using such aids as external fixation, distractors, and percutaneous
      reduction clamps before the plate can be applied. Based on the open indirect
      "biological" technique of osteosynthesis, the LISS was combined with an AO
      distractor (LISS tractor) integrated into the LISS plate. This made reduction
      possible against the plate before final fixation of the LISS plate. The LISS
      tractor concept was validated in three patients and we present the technique
      here. No malalignments > 5 degrees occurred. Fluoroscopy lasted 3.0 min (range:
      2.1-4.5) and the operation 125 min (range: 90-150). Modification of the well
      known LISS technique by integrating the distractor into the LISS plate to
      simplify reduction and to provide temporary retention of the fracture has the
      potential to reduce the fluoroscopy time, the operation time, the rate of
      malalignments, and the learning curve for this MIPO technique.

PMID- 11460460
TI  - [Locally pedicled muscle flap-plasty in traumatology of the lower leg].

PMID- 11460461
TI  - [Esophageal perforation by osteosynthesis material after ventral spondylodesis of
      the cervical spine].
AB  - Esophageal perforation after cervical spine surgery is a rare complication. Based
      on the case of a 77-year-old female patient with a late, asymptomatic esophageal
      perforation after a ventral spondylodesis of the cervical spine, the symptoms,
      diagnostics, and therapy of this complication are discussed. The therapy of
      choice is the operation. Nonoperative therapy should only be chosen--like in our
      case--for special indications. An esophageal perforation with symptoms should be
      treated operatively. Our patient was treated conservatively in consideration of
      her age and missing symptoms.

PMID- 11460462
TI  - [Post-traumatic osteoid osteoma. Case report and review of the literature].
AB  - Osteoid osteoma is a painful benign bone neoplasm that is rarely described after
      trauma but should be suspected. A case of osteoid osteoma 19 years after a tibial
      fracture is presented. The patient had pain in the tibia for 6 years before the
      osteoid osteoma was confirmed. He had been operated on twice for suspected
      osteomyelitis although the clinical symptoms suggested an osteoid osteoma. The
      radiographic appearance as well as a bone scan confirmed the diagnosis. Removal
      of the nidus resulted in immediate pain relief. A precise preoperative diagnosis
      of the lesion based on clinical findings, standard radiographs, high-resolution
      CT, and bone scan is mandatory. It is important to recognize this uncommon entity
      to avoid morbidity associated with a prolonged delay in diagnosis.

PMID- 11460463
TI  - [Prevention of hip joint fractures in the elderly using an external hip
      protector].

PMID- 11460464
TI  - Fibrinogen: evolution of the structure-function concept. Keynote address at
      fibrinogen 2000 congress.
AB  - Coagulation of blood is such an evident phenomenon that its observation can be
      traced back to earliest historical times. The great philosophers and physicians
      of antiquity discussed and provided interesting explanations. However, it was not
      until the end of the seventeenth century that the structural component of the
      blood clot was described by Malpighi as a white fibrous substance. In the middle
      of the nineteenth century this was identified as a constituent of pathological
      thrombi and given the name fibrin. At about that time its precursor in blood,
      fibrinogen, was isolated in a highly purified form by Hammarsten who suggested
      that, preceding fibrin formation, activation of fibrinogen by thrombin occurred
      by limited proteolysis. The activation mechanism was eventually clarified in the
      1950s. It was shown to proceed in two discrete steps, by removal of low molecular
      weight activation peptides. Ferry postulated, based on physicochemical
      observations, that the activated molecules aligned in a half-staggered fashion to
      form polymers. The rapid post-war development of biochemical technology permitted
      evaluation of the primary structure of fibrinogen. With that followed
      identification of molecular domains in the activated firbinogen molecules that
      participate in polymer formation, crosslinking of polymeric structures, and
      domains for cellular attachment. Crystallization of fragments and, recently, of
      the entire molecule has confirmed and extended this knowledge. Lately, it has
      also been possible to obtain detailed information on the architecture of the
      fiber network in the fibrin gel. The gel structure is primarily determined by the
      initial rate of fibrinogen activation, but without infringement of this primary
      rule, several factors in blood may modulate the structure. Fibrinogen and fibrin
      play important roles in normal hemostasis, wound healing, and pathological
      processes, such as thrombosis and atherosclerosis.

PMID- 11460465
TI  - Insight from studies with recombinant fibrinogens.
AB  - Using a two-step cloning strategy, we have synthesized more than 20 variant human
      fibrinogens for biochemical studies. In preliminary experiments we showed that
      normal fibrinogen produced in CHO cells serves as an accurate model for plasma
      fibrinogen. We focus here on those variants whose characterization has provided
      insight into the mechanism of thrombin-catalyzed polymerization. Analysis of N
      terminal variants showed that thrombin specificity dictates the ordered release
      of fibrinopeptides. Nevertheless, analysis of C-terminal variants indicated that
      fibrinopeptide B (FpB) release is dependent on polymerization. Changes in the a
      polymerization site and the high-affinity calcium-binding site were associated
      with a complete loss of polymerization. These experiments showed that alterations
      in the calcium-binding site influenced function of the a site; in contrast,
      alterations in the a site did not alter calcium binding. Analysis of variants in
      the N-terminus of the B beta chain provided the first direct evidence that this
      region impacts predominantly on lateral aggregation, as has long been presumed.
      These experiments also suggested that lateral aggregation facilitated by this
      region proceeds without the release of FpB. From these studies we learned that
      individual sites within fibrinogen do not function in isolation. We conclude that
      thrombin-catalyzed polymerization is mediated by a continuum of concerted
      interactions.

PMID- 11460466
TI  - The structure and biological features of fibrinogen and fibrin.
AB  - Fibrinogen and fibrin play important, overlapping roles in blood clotting,
      fibrinolysis, cellular and matrix interactions, inflammation, wound healing, and
      neoplasia. These events are regulated to a large extent by fibrin formation
      itself and by complementary interactions between specific binding sites on
      fibrin(ogen) and extrinsic molecules including proenzymes, clotting factors,
      enzyme inhibitors, and cell receptors. Fibrinogen is comprised of two sets of
      three polypeptide chains termed A alpha, B beta, and gamma, that are joined by
      disulfide bridging within the N-terminal E domain. The molecules are elongated 45
      nm structures consisting of two outer D domains, each connected to a central E
      domain by a coiled-coil segment. These domains contain constitutive binding sites
      that participate in fibrinogen conversion to fibrin, fibrin assembly,
      crosslinking, and platelet interactions (e.g., thrombin substrate, Da, Db, gamma
      XL, D:D, alpha C, gamma A chain platelet receptor) as well as sites that are
      available after fibrinopeptide cleavage (e.g., E domain low affinity non
      substrate thrombin binding site); or that become exposed as a consequence of the
      polymerization process (e.g., tPA-dependent plasminogen activation). A
      constitutive plasma factor XIII binding site and a high affinity non-substrate
      thrombin binding site are located on variant gamma' chains that comprise a minor
      proportion of the gamma chain population. Initiation of fibrin assembly by
      thrombin-mediated cleavage of fibrinopeptide A from A alpha chains exposes two EA
      polymerization sites, and subsequent fibrinopeptide B cleavage exposes two EB
      polymerization sites that can also interact with platelets, fibroblasts, and
      endothelial cells. Fibrin generation leads to end-to-middle intermolecular Da to
      EA associations, resulting in linear double-stranded fibrils and equilaterally
      branched trimolecular fibril junctions. Side-to-side fibril convergence results
      in bilateral network branches and multistranded thick fiber cables.
      Concomitantly, factor XIII or thrombin-activated factor XIIIa introduce
      intermolecular covalent epsilon-(gamma glutamyl)lysine bonds into these polymers,
      first creating gamma dimers between properly aligned C-terminal gamma XL sites,
      which are positioned transversely between the two strands of each fibrin fibril.
      Later, crosslinks form mainly between complementary sites on alpha chains
      (forming alpha-polymers), and even more slowly among gamma dimers to create
      higher order crosslinked gamma trimers and tetramers, to complete the mature
      network structure.

PMID- 11460467
TI  - Synthesis of a mouse model of the dysfibrinogen Vlissingen/Frankfurt IV.
AB  - The dysfibrinogen Vlissingen/Frankfurt IV is characterized as a deletion of
      Asn319 and Asp320 from the C-terminus of the gamma-chain of fibrinogen. This
      dysfibrinogen, which was identified in several family members that are all
      heterozygous for the in-frame 6-bp deletion, is associated with both venous and
      arterial thrombosis. Here, we describe the generation of a murine model of the
      V/F IV dysfibrinogen using gene targeting of mouse gamma-chain DNA. Preliminary
      analysis shows that the human and mouse variant fibrinogens are similar:
      analogous to the human V/F IV protein, the D1 fragment of the variant mouse
      fibrinogen is partially protected from digestion in the presence of calcium or
      Gly-Pro-Arg-Pro. These heterozygous mice provide the first opportunity to examine
      the association of thrombophilia and dysfibrinogenemia in a controlled genetic
      background.

PMID- 11460468
TI  - Structural and functional role of the beta-strand insert (gamma 381-390) in the
      fibrinogen gamma-module. A "pull out" hypothesis.
AB  - Study of the folding status of the fibrinogen gamma-module (residues gamma 148
      411) revealed that its COOH-terminal beta-strand (residues gamma 381-390), that
      is normally inserted into its central domain, can be removed without destroying
      its compact structure. Based on this and other observations we propose a "pull
      out" hypothesis that suggests a mechanism for the formation of transverse gamma
      gamma crosslinks in fibrin.

PMID- 11460469
TI  - Structure and properties of clots from fibrinogen Bicetre II (gamma 308 Asn-
      >Lys). Increased permeability due to larger pores, thicker fibers, and decreased
      rigidity.
AB  - Fibrinogen Bicetre II is a dysfibrinogenemia in which there is a substitution of
      Lys for Asn at gamma 308. We have studied the polymerization of this abnormal
      fibrinogen by measurement of turbidity and have characterized clot structure by
      scanning electron microscopy, permeation, and viscoelastic measurements. The
      results of these studies demonstrate that this amino acid substitution has
      substantial effects on the structure and properties of the clot, resulting in
      clots made up of thick fibers and large pores with greatly reduced stiffness and
      increased slippage of protofibrils.

PMID- 11460470
TI  - Fibrinogen Longmont. A heterozygous abnormal fibrinogen with B beta Arg-166 to
      Cys substitution associated with defective fibrin polymerization.
AB  - B beta Arg166 to Cys substitution was identified in an abnormal fibrinogen named
      fibrinogen Longmont. The proband, a young woman, and her mother were
      heterozygous; both experienced episodes of severe hemorrhage at childbirth. The
      neo-Cys residues were found to be disulfide-bridged to either an isolated Cys
      amino acid or to the corresponding Cys residue of another abnormal fibrinogen
      molecule, forming dimers. Thrombin and batroxobin induced fibrin polymerization
      were impaired, despite normal release of fibrinopeptides A and B. Moreover, the
      polymerization defect was not corrected by removing the dimeric species or adding
      calcium. Fibrinogen Longmont had normal polymerization site a, as evidenced by
      normal GPRP-peptide binding. Thus, the sites A and a can interact to form
      protofibrils, as evidenced by dynamic light scattering measurements. These
      protofibrils, however, do not associate laterally in a normal manner, leading to
      an abnormal clot formation.

PMID- 11460471
TI  - Determinants of thrombin specificity.
AB  - Thrombin recognizes a number of natural substrates that are responsible for
      important physiologic functions. Its high specificity is controlled by residues
      within the active site, and by separate recognition sites located on the surface
      of the enzyme. A number of studies have addressed the question of how thrombin
      changes its specificity from fibrinogen to protein C, switching from a
      procoagulant to an anticoagulant enzyme. Site directed mutagenesis studies have
      revealed important aspects of how this switch takes place. Specifically, residues
      W215 and E217 have emerged as key residues in controlling the interaction with
      fibrinogen in that mutation of these residues compromises the procoagulant
      function of the enzyme up to 500-fold. The loss of fibrinogen clotting reaches
      20,000-fold in the double mutant W215A/E217A, whereas protein C activation is
      compromised less than sevenfold. These findings demonstrate that thrombin
      specificity can be dissected at the molecular level using Ala-scanning
      mutagenesis and the procoagulant function of the enzyme can be abrogated
      rationally and selectively. It is now possible to extend this strategy to the
      study of other interactions of thrombin, as well as to related serine proteases.

PMID- 11460472
TI  - The fibrin intermediate, its place in the fibrinogen-fibrin transformation.
AB  - Our preceding study indicated that, in course of coagulation of human fibrinogen
      by thrombin, substantial production of the fibrin intermediate (alpha-profibrin)
      lacking only one fibrinopeptide A (FPA) precedes the formation of alpha-fibrin
      monomer lacking both FPAs. The plateau concentration of alpha-profibrin (20% of
      initial fibrinogen) appearing in reactions indicated, however, that the second
      FPA is released four times faster than the first. The study reported here
      confirms those findings, and provides new insight into the significance of
      differing rate constants for the production of alpha-profibrin and its conversion
      to alpha-fibrin. The intermediate could be isolated in a distinct electrophoretic
      band by electrophoresing partial thrombin digests at high concentrations. Its
      identity was verified by digesting it with CNBr and by demonstrating that its N
      terminal domain, the NDSK fragment, both lacks an FPA and contains an FPA, unlike
      the NDSKs of the bands from fibrin which contained no FPA or the fibrinogen band
      that lacked no FPA. The single step isolation also enabled us to confirm the 15
      20% plateau level of alpha-profibrin in course of thrombin reactions, well below
      the 37% maximum that would be expected if release of the first and second FPA
      proceeded independently with no difference in rate. The 37% maximum is observed
      in reactions with atroxin, and it is suggested that the abundant production of
      alpha-profibrin underlies the therapeutic utility of atroxin as a defibrinating
      agent. Gel chromatography procedures were optimized for isolation of alpha
      profibrin/fibrin mixtures free of fibrinogen, the final step of which involves
      literal use of agarose gel as a filter to remove fibrin aggregates from the
      fibrinogen free fractions (aggregates are left behind in gel filtration, rather
      than their moving ahead in gel chromatography). Unlike human fibrinogen, rabbit
      fibrinogen does not yield much alpha-profibrin in course of its conversion to
      fibrin, less than 10% as determined by electrophoresis and comparison with
      abundant production with atroxin. This low production of alpha-profibrin
      conformed with conclusions from our early studies on the generalized Shwartzman
      reaction in rabbits, and we now infer that the low production of alpha-profibrin
      and rapid conversion to fibrin by rabbit fibrinogen underlies the unparalleled
      susceptibility of these animals toward fibrinoid formation in the generalized
      Shwartzman reaction.

PMID- 11460473
TI  - Early events in the polymerization of fibrin.
AB  - The early events in the thrombin-induced formation of fibrin have been studied by
      the use of stopped-flow multiangle laser light scattering (SF-MALLS). This
      technological advancement has allowed the recovering, as a function of time with
      a resolution of about 0.5 sec, of the mean square radius of gyration (Rg2)z and
      of the molecular weight Mw, and to place an upper bound to the values of the
      mass/unit length ML. The ionic strength, pH and salt type conditions investigated
      were all close to physiological, starting with a 50 mM Tris, 104 mM NaCl, pH 7.4
      buffer (TBS), to which either 1 mM EDTA-Na2 or 2.5 mM CaCl2 were also added.
      Fibrinogen was 0.2-0.3 mg/ml and rate-limiting concentrations of thrombin were
      used (0.05-0.25 NIH units/mg fibrinogen). By plotting (Rg2)z and ML versus Mw on
      log-log scales, runs proceeding at different velocities and under different
      solvent conditions could be compared and confronted with model curves. It was
      found that: (1) within this thrombin range, the mechanism of association does not
      depend on its concentration, nor on the buffers employed; (2) the (Rg2)z versus
      Mw curves could all be reasonably fitted with a bifunctional polycondensation
      scheme involving semiflexible worm-like, double-stranded, half-staggered polymers
      with persistence length between 200-600 nm, provided that a ratio Q = 16 between
      the rate of release of the two fibrinopeptides A was employed; (3) the ML versus
      Mw data seemed more compatible with lower Q values (4 < Q < 8), but their
      uncertainty prevented a better assessment of this issue; the formation of
      fibrinogen-fibrin monomer complexes may also play a role in the polymer
      distributions; (4) in the very early stages (e.g., when Mw < 7 x 10(5)), the
      (Rg2)z versus Mw data were fitted well only in TBS and at the lowest thrombin
      concentration, suggesting that a transient, either sequential or concurrent fast
      second mechanism, involving longer and thinner polymers, may be at work.

PMID- 11460474
TI  - Conformational changes upon conversion of fibrinogen into fibrin. The mechanisms
      of exposure of cryptic sites.
AB  - Conformational changes upon conversion of fibrinogen to fibrin result in the
      exposure of multiple binding sites that provide its interaction with various
      proteins and cells and, thus, its participation in a number of physiological and
      pathological processes. Here we focus on conformational changes in the fibrinogen
      D regions (domains) and alpha C-domains that are directly involved in
      intermolecular interactions upon fibrin assembly. According to the current view,
      two alpha C-domains that interact intramolecularly in fibrinogen undergo an intra
      to intermolecular switch to form alpha C-polymers in fibrin. The availability of
      recombinant fragments that correspond to the alpha C-domain made it possible to
      further clarify this mechanism and to reveal novel cryptic sites in this domain
      for plasminogen and its activator tPA, whose exposure may play an important role
      in the regulation of fibrinolysis. To elucidate the mechanism of exposure of
      cryptic sites in the D regions, we tested the accessibility of their fibrin
      specific epitopes (A alpha 148-160 and gamma 312-324) that are also involved in
      binding of plasminogen and tPA, in several fragments derived from fibrinogen
      (fragment D), and crosslinked fibrin (fragment D-D and its non-covalent complex
      with the E1 fragment, D-D:E1). Neither D nor D-D bound tPA, plasminogen, or anti
      A alpha 148-160 and anti-gamma 312-324 monoclonal antibodies. At the same time
      both epitopes became accessible in the D-D:E1 complex. Melting of D and D-D
      revealed that their domains have the same stability while in the D-D:E1 complex
      they became more stable. These results indicate that upon fibrin assembly, driven
      primarily by the interaction between complementary binding sites of the E and two
      D regions, the latter undergo conformational changes that cause the exposure of
      their cryptic sites. They also suggest that the fibrin specific conformation of
      the D regions is preserved in the D-D:E1 complex.

PMID- 11460475
TI  - Polymerization site a function dependence on structural integrity of its nearby
      calcium binding site.
AB  - To explore the functional relationship between the polymerization site a and the
      nearby high affinity calcium binding site, we analyzed four variant fibrinogens
      with substitutions at these sites: gamma D364A in the a site and gamma D318A,
      gamma D320A, and gamma D318 + gamma D320A in the Ca2+ site. In all cases
      fibrinopeptide A release was normal and thrombin catalyzed polymerization was
      markedly impaired (unpublished observations). We examined the functional
      connection between the Ca2+ site and the a site by testing for plasmin protection
      in the presence of Ca2+ or the a site peptide ligand GPRP. SDS-PAGE analysis of
      the products showed that gamma D364A fibrinogen was protected from plasmin
      cleavage by Ca2+ but not by the GPRP peptide. In contrast, neither Ca2+ nor the
      GPRP peptide protected gamma D318A, gamma D320A, or gamma D318 + gamma D320A
      fibrinogens from complete plasmin cleavage. These results suggest that the
      structural integrity of the calcium binding site is required for expression of
      the a site. In contrast, the structural integrity of the a site has no functional
      consequence on Ca2+ binding to this high affinity site.

PMID- 11460476
TI  - Fibrin formation and proteolysis during ancrod treatment. Evidence for des-A
      profibrin formation and thrombin independent factor XIII activity.
AB  - Ancrod is a purified fraction of venom from the Malayan pit viper Calloselasma
      rhodostoma, containing a serine protease that cleaves fibrinopeptides A from
      fibrinogen. We report on a study that involved intravenous and subcutaneous
      application of ancrod in healthy subjects in which it was shown that ancrod
      induces the formation of desAA-fibrin complexes that are partially crosslinked by
      factor XIII proenzyme, and act as cofactor in tPA induced plasminogen activation.
      The plasmin generated degrades fibrin, as well as fibrinogen, leading to the
      appearance of large amounts of fibrinogen and fibrin degradation products in the
      circulation, including fragment D-dimer. At low concentrations of ancrod,
      formation of desAA-fibrin is preceded by production of desA-profibrin, lacking
      only one fibrinopeptide A.

PMID- 11460477
TI  - Characterization of crosslinking sites in fibrinogen for plasminogen activator
      inhibitor 2 (PAI-2).
AB  - PAI-2 is a serpin that can be crosslinked to fibrin(ogen) via the Gln-Gln-Ile-Gln
      sequence (residues 83-86). We have characterized the lysine residues in
      fibrinogen to which PAI-2 is crosslinked by tissue transglutaminase and factor
      XIIIa. There was no competition with the crosslinking of alpha 2-antiplasmin,
      another inhibitor of fibrinolysis, which was specific for Lys 303 in the A alpha
      chain. PAI-2 was crosslinked to several lysine residues, all in the A alpha
      chain, 148, 176, 183, 230, 413, and 457, but not to Lys 303. The contrast with
      alpha 2-antiplasmin was clear from studies with truncated fibrinogens and
      competition by peptides. This was confirmed and extended by mass spectrometry of
      peptides after protease digestion of crosslinked products, which identified the
      lysine residues to which the inhibitors were crosslinked. PAI-2 remained active
      after cross-linking and inhibited fibrin breakdown, even by two-chain t-PA. Thus,
      a second inhibitor of fibrinolysis, in addition to alpha 2-antiplasmin, is
      crosslinked to fibrin and protects it from lysis.

PMID- 11460478
TI  - The formation of beta fibrin requires a functional a site.
AB  - We used recombinant fibrinogens in which the a site is disrupted to examine beta
      fibrin formation in the absence of a functional a site. Our variants have only b
      sites available, and they showed no evidence of fibrin polymer formation after
      cleavage of FpB with venzyme. We conclude that B-b interactions are not strong
      enough to induce clot formation. Our studies do not rule out the involvement of b
      in the formation of beta-fibrin, yet they do provide evidence that a is likely to
      be essential in the formation of beta-fibrin.

PMID- 11460479
TI  - Mode of perturbation of Asahi fibrin assembly by the extra oligosaccharides.
AB  - Steric hindrance by the backbone of extra oligosaccharides at gamma-Asn 308 may
      cause the repulsive force to widen the junction at the D:D interface, and thus,
      interfere with the longitudinal elongation and lateral association of
      protofibrils.

PMID- 11460480
TI  - Elements of the fibrinolytic system.
AB  - The blood fibrinolytic system comprises an inactive proenzyme, plasminogen, that
      can be converted to the active enzyme, plasmin. Plasmin degrades fibrin into
      soluble fibrin degradation products, by two physiological plasminogen activators
      (PA), the tissue type PA (t-PA) and the urokinase type PA (u-PA). t-PA mediated
      plasminogen activation is mainly involved in the dissolution of fibrin in the
      circulation. u-PA binds to a specific cellular receptor (u-PAR), resulting in
      enhanced activation of cell bound plasminogen. Inhibition of the fibrinolytic
      system may occur either at the level of the PA, by specific plasminogen activator
      inhibitors (PAI), or at the level of plasmin, mainly by alpha 2-antiplasmin.
      Several molecular interactions have been observed between the fibrinolytic and
      the matrix metalloproteinase (MMP) system; both systems may cooperate in
      generating proteolytic activity. Thus, stromelysin-1 (MMP-3) cleaves a 55-kDa
      kringle 1-4 fragment, containing the lysine binding site(s) involved in cellular
      binding, from plasminogen and removes a 17-kDa NH2-terminal fragment, containing
      the cellular receptor binding site, from urokinase (u-PA). Thereby, MMP-3 may
      downregulate cell associated plasmin activity by decreasing the amount of
      activatable plasminogen, without affecting cell bound u-PA activity.

PMID- 11460481
TI  - Fibrin-mediated plasminogen activation.
AB  - Fibrin, but not fibrinogen, enhances the rate of activation of plasminogen by
      tissue type plasminogen activator (t-PA). Studies with enzymatic and chemical
      fragments of fibrinogen showed that several sites in fibrinogen are involved in
      this rate enhancement; these are, A alpha 148-160 (located in CNBr fragment FCB
      2), and FCB-5 (a CNBr fragment comprising gamma 312-324), and recently discovered
      sites in the fibrinogen alpha C domains. All these sites are buried in
      fibrinogen, but exposed in fibrin and some fibrinogen fragments. For the first
      two of these, located in the D-domains, this was shown by the fact that
      monoclonal antibodies against A alpha 148-160 and gamma 312-324 bind to fibrin
      and rate enhancing fibrin(ogen) fragments, but not to fibrinogen. Direct binding
      studies indicate that at physiological concentrations plasminogen binds to FCB-2,
      and t-PA to FCB-5. More detailed studies have demonstrated the importance of
      residues A alpha-157 and A alpha-152, and that the minimum stretch with rate
      enhancing properties is A alpha 154-159. The sites in the alpha C domains await
      further identification. With the recently reported three-dimensional structure of
      fragments D and D-dimer it is now possible to explain these findings at the
      molecular level. Molecular calculations and experimental data show that the site
      A alpha 148-160 in fibrinogen is covered among others by a part of the A alpha
      chain (A alpha 166-195) that forms an alpha-helix, and by a globular domain
      formed by the beta-chain. On fibrin formation, the last two may move away, and
      give access to A alpha 148-160. It is conceivable that in the alpha C domain
      sites are involved in the early phases of fibrinolysis. The site A alpha 148-160
      and that in FCB-5 may be more important at later stages. It is also clear that
      fibrin polymerization is important. This polymerization has probably several
      effects: exposure of the rate enhancing sites; mutual positioning of the t-PA and
      plasminogen binding sites; a concentrating effect of t-PA and plasminogen on the
      fibrin surface; effects on the kinetic properties of t-PA and plasminogen. These
      effects together explain the rate enhancement.

PMID- 11460482
TI  - Modulation of fibrin cofactor activity in plasminogen activation.
AB  - Fibrin is a cofactor for the formation of plasmin from plasminogen as catalyzed
      by tissue plasminogen activator. Initial cleavages of fibrin by plasmin
      upregulates the cofactor activity of fibrin by exposing carboxyl terminal lysine
      residues. This effect is eliminated by a carboxypeptidase B-like enzyme generated
      from the precursor, thrombin activatable fibrinolysis inhibitor (TAFI) that is
      generated by thrombin during the formation of fibrin. Thus, TAFI and its
      activation to TAFIa create a link between the coagulation and fibrinolytic
      cascade, such that activation of the former suppresses the latter. Complete
      solubilization of fibrin results in a family of very large fibrin degradation
      products. These also have very substantial tissue plasminogen activator cofactor
      activity that is very highly downregulated by TAFIa.

PMID- 11460483
TI  - Inhibition of fibrinolysis by lipoprotein(a).
AB  - A high plasma concentration of lipoprotein Lp(a) is now considered to be a major
      and independent risk factor for cerebro- and cardiovascular atherothrombosis. The
      mechanism by which Lp(a) may favour this pathological state may be related to its
      particular structure, a plasminogen-like glycoprotein, apo(a), that is disulfide
      linked to the apo B100 of an atherogenic LDL-like particle. Apo(a) exists in
      several isoforms defined by a variable number of copies of plasminogen-like
      kringle 4 and single copies of kringle 5 and the catalytic region. At least one
      of the plasminogen-like kringle 4 copies present in apo(a) (kringle IV type 10)
      contains a lysine binding site (LBS) that is similar to that of plasminogen. This
      structure allows binding of these proteins to fibrin and cell membranes.
      Plasminogen thus bound is cleaved at Arg561-Val562 by plasminogen activators and
      transformed into plasmin. This mechanism ensures fibrinolysis and pericellular
      proteolysis. In apo(a) a Ser-Ile substitution at the Arg-Val plasminogen
      activation cleavage site prevents its transformation into a plasmin-like enzyme.
      Because of this structural/functional homology and enzymatic difference, Lp(a)
      may compete with plasminogen for binding to lysine residues and impair, thereby,
      fibrinolysis and pericellular proteolysis. High concentrations of Lp(a) in plasma
      may, therefore, represent a potential source of antifibrinolytic activity.
      Indeed, we have recently shown that during the course of the nephrotic syndrome
      the amount of plasminogen bound and plasmin formed at the surface of fibrin are
      directly related to in vivo variations in the circulating concentration of Lp(a)
      (Arterioscler. Thromb. Vasc. Biol., 2000, 20: 575-584; Thromb. Haemost., 1999,
      82: 121-127). This antifibrinolytic effect is primarily defined by the size of
      the apo(a) polymorphs, which show heterogeneity in their fibrin-binding activity-
      only small size isoforms display high affinity binding to fibrin (Biochemistry,
      1995, 34: 13353-13358). Thus, in heterozygous subjects the amount of Lp(a) or
      plasminogen bound to fibrin is a function of the affinity of each of the apo(a)
      isoforms and of their concentration relative to each other and to plasminogen.
      The real risk factor is, therefore, the Lp(a) subpopulation with high affinity
      for fibrin. According to this concept, some Lp(a) phenotypes may not be related
      to atherothrombosis and, therefore, high Lp(a) in some individuals might not
      represent a risk factor for cardiovascular disease. In agreement with these data,
      it has been recently reported that Lp(a) particles containing low molecular mass
      apo(a) emerged as one of the leading risk conditions in advanced stenotic
      atherosclerosis (Circulation, 1999, 100: 1154-1160). The predictive value of high
      Lp(a) as a risk factor, therefore, depends on the relative concentration of Lp(a)
      particles containing small apo(a) isoforms with the highest affinity for fibrin.
      Within this context, the development of agents able to selectively neutralise the
      antifibrinolytic activity of Lp(a), offers new perspectives in the prevention and
      treatment of the cardiovascular risk associated with high concentrations of
      thrombogenic Lp(a).

PMID- 11460484
TI  - Genetic manipulation of fibrinogen and fibrinolysis in mice.
AB  - Vascular integrity is maintained by a sophisticated system of circulating and
      cell associated hemostatic factors that control local platelet deposition, the
      conversion of soluble fibrinogen to an insoluble fibrin polymer, and the
      dissolution of fibrin matrices. However, hemostatic factors are likely to be
      biologically more important than merely maintaining vascular patency and
      controlling blood loss. Specific hemostatic factors have been associated with a
      wide spectrum of physiological processes, including development, reproduction,
      tissue remodeling, wound repair, angiogenesis, and the inflammatory response.
      Similarly, it has been proposed that hemostatic factors are important
      determinants of a variety of pathological processes, including vessel wall
      disease, tumor dissemination, infectious disease, and inflammatory diseases of
      the joint, lung, and kidney. The development of gene targeted mice either lacking
      or expressing modified forms of selected hemostatic factors has provided a
      valuable opportunity to test prevailing hypotheses regarding the biological roles
      of key coagulation and fibrinolytic system components in vivo. Genetic analyses
      of fibrin(ogen) and its interacting factors in transgenic mice have proven to be
      particularly illuminating, often challenging long standing concepts. This review
      summarizes the key findings made in recent studies of gene targeted mice with
      single and combined deficits in fibrinogen and fibrinolytic factors. Studies
      illustrating the role and interplay of these factors in disease progression are
      highlighted.

PMID- 11460485
TI  - Factor XIII: structure, activation, and interactions with fibrinogen and fibrin.
AB  - Fibrin stabilizing factor (factor XIII or FXIII) plays a critical role in the
      generation of a viable hemostatic plug. Following exposure to thrombin and
      calcium, the zymogen is activated to FXIIIa that, in turn, catalyzes the
      formation of N epsilon(gamma-glutamyl)lysine protein-to-protein side chain
      bridges within the clot network. Introduction of these covalent crosslinks
      greatly augments the viscoelastic storage modulus of the structure and its
      resistance to fibrinolytic enzymes. Analysis of the individual reaction steps and
      regulatory control mechanisms involved in clot stabilization enabled us to
      reconstruct the entire physiological process. This also serves as a guide for the
      differential diagnosis of the variety of molecular defects of fibrin
      stabilization.

PMID- 11460486
TI  - Crystal structure studies on fibrinogen and fibrin.
AB  - X-ray crystallography studies on fragments D and double-D from human fibrinogen
      and fibrin have revealed the details of knob-hole interactions between fibrin
      units, as well as the nature of the association at their ends. More recently, a
      lower-resolution structure of native chicken fibrinogen has provided details
      about the structure of the central domain, and particularly the arrangement of
      disulfide bonds. Parts of the fibrinogen molecule are so flexible that they have
      not been visualized in electron density maps. The elusive regions include the
      alpha C domain, the amino-terminal segments of the alpha and beta chains, and the
      carboxyl-terminal segments of the gamma chains. Nonetheless, when all the
      structural data are considered together, it is possible to construct a realistic
      model not only of a fibrinogen molecule but also of a fibrin protofibril.

PMID- 11460487
TI  - The structure and function of the alpha C domains of fibrinogen.
AB  - The alpha C domains have been localized on fibrinogen and fibrin. Several model
      systems have been developed to study their functions. Analysis of the amino acid
      sequence of the alpha C domains suggested that each is made up of a globular and
      an extended portion. Microcalorimetry confirmed this result and showed that the
      two alpha C domains interact intramolecularly. Electron microscopy of fibrinogen
      with a monoclonal antibody to the alpha C domains demonstrated that these regions
      normally interact with the central portion of the molecule. In the conversion
      from fibrinogen to fibrin there is a large scale conformational change, such that
      the alpha C domains dissociate from the central region and are available for
      intermolecular interaction. Experiments with highly purified and well
      characterized fragment X monomer, missing either one or both of the alpha C
      domains, indicate that intermolecular interactions between alpha C domains are
      important for the enhancement of lateral aggregation during fibrin
      polymerization. Isolated alpha C fragments polymerized at neutral pH and
      interacted with the alpha C domains of fibrin monomer to influence clot
      formation. Several dysfibrinogenemias in which there are amino acid substitutions
      in, or truncations of, the alpha C domains revealed that these changes can have
      dramatic effects on polymerization and clot structure. The polymerization of A
      alpha 251 recombinant fibrinogen, that contains A alpha chains truncated at
      residue 251, was altered, as were the mechanical properties and the rate of
      fibrinolysis of the clots. Altogether, these results help to define the role of
      the alpha C domains in determining the structure and properties of clots.

PMID- 11460488
TI  - Fibrinogen alpha C domains contain cryptic plasminogen and tPA binding sites.
AB  - Surface plasmon resonance and ELISA experiments revealed that recombinant
      fibrinogen alpha C fragment (residues A alpha 221-610) corresponding to the alpha
      C domain binds tPA and plasminogen with high affinity. This binding was found to
      be Lys-dependent and occurred via independent binding sites. Study with truncated
      variants of the alpha C fragment located these sites in its COOH-terminal half.
      Binding of tPA and plasminogen to these sites stimulated activation of the latter
      whereas proteolytic degradation of the alpha C fragment reduced this effect
      substantially, suggesting the importance of the alpha C domains in regulation of
      fibrinolysis.

PMID- 11460489
TI  - Clot lysis of variant recombinant fibrinogens confirms that fiber diameter is a
      major determinant of lysis rate.
AB  - Previous studies have suggested that clots with thinner fiber diameter lyse at
      slower rates than clots with thicker fiber diameter. We examined lysis of fibrin
      clots formed from three variant fibrinogens, each with substitutions in the N
      terminal region of the B beta chain. When we measured lysis as the rate of
      decrease in turbidity at 350 nm, we found that the rate of lysis was slower than
      normal for clots with thinner fibers. We noted, however, that the time to
      complete lysis was the same for all clots. Thus, when the data were considered as
      the percent of lysis with time, we found that the curves were the same as normal.
      We suggest that a complete and accurate characterization of clot dissolution
      requires comparison of normalized lysis rates.

PMID- 11460490
TI  - Crosslinking of alpha 2-antiplasmin to fibrin.
AB  - Human alpha 2-antiplasmin (alpha 2AP) is the primary inhibitor of plasmin
      mediated fibrinolysis and is an efficient substrate of activated factor XIII
      (FXIIIa). Among 452 amino acid residues in alpha 2AP, Gln2 is believed to be the
      sole FXIIIa-reactive site that participates in crosslinking alpha 2AP to fibrin.
      We studied the effect of mutating Gln2 on the ability of FXIIIa to catalyze
      crosslinking of alpha 2AP to fibrin. By FXIIIa catalysis, [14C]methylamine was
      incorporated into a Q2A-alpha 2AP mutant in which Gln2 (Q) was replaced by Ala
      (A), thereby indicating that wildtype alpha 2AP has more than one FXIIIa-reactive
      site. To identify the FXIIIa-reactive sites in alpha 2AP, wildtype alpha 2AP and
      Q2A-alpha 2AP were labeled with 5-(biotinamido)pentylamine by FXIIIa. Each
      labeled alpha 2AP was digested with trypsin and applied to an avidin affinity
      column to capture labeled peptides. Edman sequencing and mass analysis of each
      labeled peptide showed that out of 35 Gln residues in wildtype alpha 2AP, four
      were labeled with the following order of efficiency: Gln2 > Gln21 > Gln419 >
      Gln447. Q2A-alpha 2AP was also labeled at the three minor sites, Gln21 > Gln419 >
      Gln447. Q2A-alpha 2AP became crosslinked to fibirin(ogen) by FXIIIa catalysis at
      approximately one-tenth the rate of wt-alpha 2AP. These results demonstrate that
      alpha 2AP has one primary (Gln2) and three minor substrate sites for FXIIIa and
      that the three minor sites identified in this study can also participate in
      crosslink formation between alpha 2AP and fibrin, but at a much lower efficiency
      than the Gln2 site.

PMID- 11460491
TI  - Platelet-fibrinogen interactions.
AB  - Binding of fibrinogen to GPIIb-IIIa on agonist-stimulated platelets results in
      platelet aggregation, presumably by crosslinking adjacent activated platelets.
      Although unactivated platelets express numerous copies of GPIIb-IIIa on their
      surface, spontaneous, and potentially deleterious, platelet aggregation is
      prevented by tightly regulating the fibrinogen binding activity of GPIIb-IIIa.
      Preliminary evidence suggests that it is the submembranous actin or actin
      associated proteins that constrains GPIIb-IIIa in a low affinity state and that
      relief of this constraint by initiating actin filament turnover enables GPIIb
      IIIa to bind fibrinogen. Two regions of the fibrinogen alpha chain that contain
      an RGD motif, as well as the carboxyl-terminus of the fibrinogen gamma chain,
      represent potential binding sites for GPIIb-IIIa in the fibrinogen molecule.
      However, ultrastructural studies using purified fibrinogen and GPIIb-IIIa, and
      studies using recombinant fibrinogen in which the RGD and relevant gamma chain
      motifs were mutated indicate that sequences located at the carboxyl-terminal end
      of the gamma chain mediates fibrinogen binding to GPIIb-IIIa. There is evidence
      that fibrinogen itself binds to regions in the amino terminal portions of both
      GPIIb and GPIIIa and that the sites interacting with the fibrinogen gamma chain
      and with RGD-containing peptides are spatially distinct. Nonetheless, there
      appears to be allosteric linkage between these sites, accounting for the ability
      of RGD-containing peptides to inhibit platelet aggregation and arterial
      thrombosis.

PMID- 11460492
TI  - Fibrin and wound healing.
AB  - Although hemostasis is the major role of fibrin in wound repair, once the clot is
      present the wound cells must deal with it.  The invasion and clearing of fibrin
      by these cells involves multiple complex processes that may go array XXX and
      delay wound repair.  A good example, of the latter is leg ulcers.  These chronic
      wounds contain a plethora of proteases that digest fibronectin and growth factors
      in the fibrin clot resulting in a corrupt provisional matrix that no longer
      supports reepithelialization or granulation tissue formation.  Every good wound
      care provider knows that these wounds will not heal unless the corrupt matrix is
      removed by vigorous debridement that stimulates the accumulation of a competent
      provisional matrix.

PMID- 11460493
TI  - Recognition of fibrinogen by leukocyte integrins.
AB  - Numerous studies have provided evidence that fibrinogen plays a multifaceted role
      in the immune and inflammatory response. The ability of fibrinogen to participate
      in the inflammatory response depends on its specific interaction with leukocyte
      cell surface adhesion receptors, integrins. Two leukocyte integrins, alpha M beta
      2 (CD11b/CD18, Mac-1) and alpha X beta 2 (CD11c/CD18, p150,95), are the main
      fibrinogen receptors expressed on neutrophils, monocytes, macrophages and several
      subsets of lymphocytes. The recognition site for alpha M beta 2 has been
      previously mapped to the carboxyl-terminal globular gamma C domains (gamma 143
      411) and two sequences, gamma 190-202 (P1) and gamma 377-395 (P2), were
      implicated as the putative binding sites. We now demonstrate that a second
      leukocyte integrin, alpha X beta 2, which is highly homologous to alpha M beta 2,
      mediates adhesion of the alpha X beta 2-bearing cells to the D fragment and to
      the recombinant gamma-module, gamma 143-411. Within the gamma C domain, alpha X
      beta 2 may recognize P1 and P2 sequences since synthetic peptides duplicating
      these sequences effectively inhibits adhesion of the alpha X beta 2-expressing
      cells to the D fragment. In addition, neutrophil inhibitory factor, NIF, a potent
      inhibitor of alpha X beta 2, also inhibited alpha X beta 2-mediated cell
      adhesion. These data suggest that recognition of the gamma C domain of fibrinogen
      by alpha M beta 2 and alpha X beta 2 may have common structural requirements.

PMID- 11460494
TI  - Interaction of fibrin with VE-cadherin.
AB  - The conversion of fibrinogen into fibrin and the association of fibrin(ogen) with
      activated platelets play a fundamental role in hemostasis because their
      interaction with the injured vessel prevents blood extravasation. Platelet
      aggregates and fibrin also participate in the occlusion of the vascular lumen in
      pathological conditions. Fibrin II also promotes the formation of new blood
      vessels, for example, during wound healing and tumor growth. Using an in vitro
      assay, we have studied the mechanism by which fibrin II induces formation of
      capillaries. Generation of fibrin II on top of an endothelial cell monolayer
      rapidly rearranged the ECs into a capillary network. In contrast, neither fibrin
      I nor fibrin 325 induced these morphogenetic changes, indicating that exposure of
      the N-terminal peptide beta 15-42 is involved in this process. Binding studies,
      using the N-terminal fragment of fibrin (NDSK II), showed that NDSK II binds to
      EC with high affinity, but neither NDSK nor NDSK325 bound specifically. Binding
      of NDSK II to endothelial cells was blocked with an antibody to VE-cadherin.
      Direct association of NDSK II and VE-cadherin was also demonstrated in a VE
      cadherin antibody capture assay. NDSK II bound specifically with the captured VE
      cadherin but NDSK or NDSK 325 did not associate with VE-cadherin. Moreover,
      fibrin II associated with EC VE-cadherin and this interaction triggered the
      formation of capillary-like structures. A better understanding of the cellular
      responses to fibrin, identification of the fibrin binding site within VE-cadherin
      and the intracellular signaling that follows this interaction, could yield
      important information that may translate into better control of the angiogenic
      process.

PMID- 11460495
TI  - Tumors and fibrinogen. The role of fibrinogen as an extracellular matrix protein.
AB  - The progression of a tumor from benign and localized to invasive and metastatic
      growth is the major cause of poor clinical outcome in cancer patients. Much like
      in a healing wound, the deposition of fibrin(ogen), along with other adhesive
      glycoproteins, into the extracellular matrix (ECM) serves as a scaffold to
      support binding of growth factors and to promote the cellular responses of
      adhesion, proliferation, and migration during angiogenesis and tumor cell growth.
      Inappropriate synthesis and deposition of ECM constituents is linked to altered
      regulation of cell proliferation, leading to tumor cell growth and malignant
      transformation. Fibrin deposition occurs within the stroma of a majority of tumor
      types. In contrast, abundant FBG, not fibrin, is present within the stroma of
      breast cancers. It is thought to originate from exudation of plasma FBG and
      subsequent deposition into the tumor stroma and not endogenous synthesis and
      secretion of FBG by breast tumor cells. However, we show that MCF-7 human breast
      cancer cells synthesize and secrete FBG polypeptides, suggesting that the origin
      of FBG in the stroma of breast carcinoma may be due to endogenous synthesis and
      deposition. Moreover, FBG assembles into ECM as conformationally altered FBG, not
      as fibrin. Studies in our laboratory demonstrate that FBG alters the ability of
      breast cancer cells to migrate. Together, the results of studies from our
      laboratory, as well as the laboratories of others, indicate that the presence of
      fibrin(ogen) within the tumor stroma likely affects the progression of tumor cell
      growth and metastasis. This review focuses on FBG within tumors and its
      relationship with other tumor constituents, ultimately focusing on the role of
      FBG in breast cancer.

PMID- 11460496
TI  - Role of fibrin matrix in angiogenesis.
AB  - Angiogenesis, the formation of new blood vessels from existing vessels, plays an
      important role during development. In the adult, it is limited to the female
      reproductive system and to tissue repair and pathological conditions. Repair
      associated angiogenesis is usually accompanied by the presence of inflammatory
      cells, vascular leakage, and fibrin deposition. The temporary fibrin matrix acts,
      not only as a sealing matrix, but also as a scaffolding for invading leukocytes
      and endothelial cells during tissue repair. We have used a three-dimensional
      fibrin matrix to study the outgrowth of human microvascular endothelial cells in
      capillary-like tubular structures. This process is induced by the simultaneous
      addition of an angiogenic growth factor (bFGF or VEGF) and the cytokine TNF
      alpha, and is enhanced by hypoxia. It involves proteolytic activities, in
      particular cell bound urokinase/plasmin and matrix metalloproteinase activities.
      Modulation of the fibrin structure markedly affects the extent and stability of
      capillary tube formation in vitro. Preparation of fibrin at different pH (7.0
      7.8) or crosslinking of the fibrin matrix induces differences in fibrin matrix
      rigidity and structure. This is accompanied by a change in capillary ingrowth.
      Heparins, in particular low molecular weight heparins, modulate the fibrin
      structure and by this action affect angiogenesis in vitro. A mutant
      fibrinogenNieuwegein, which lacks the terminal part of the A alpha chain of
      fibrin harboring an RGD sequence and the transglutaminase sequence, provided
      additional evidence that the structure of fibrin is an important determinant for
      angiogenesis. These findings may have impact on improving wound healing and on
      influencing angiogenesis in malignancies with a fibrinous stroma.

PMID- 11460497
TI  - Fibrinogen modulates gene expression in wounded fibroblasts.
AB  - Fibrinogen (FBG) has long been regarded as serving essentially a hemostatic role
      by its conversion from a soluble, plasma protein to an insoluble fibrin gel.
      However, several extrahepatic sites of FBG biosynthesis have been identified.
      Indeed, we have demonstrated that both lung epithelial cell derived and plasma
      FBG assemble into the extracellular matrix (ECM) of epithelial cells and
      fibroblasts. In this report, we determined that FBG assembly into the ECM is a
      cell dependent step that occurs in the absence of de novo protein synthesis.
      Using an in vitro model of wound repair, we examined the role of FBG in
      modulating gene expression. Data collected from cDNA array analysis indicated
      that FBG downregulates steady state levels of fibronectin mRNA, whereas cyclin D1
      mRNA levels were upregulated in fibroblasts. Taken together, these data suggest
      that FBG may function independently of hemostasis in cellular adhesive
      interactions to modulate cellular signaling processes during wound repair.

PMID- 11460498
TI  - Contribution of the alpha EC domain to the structure and function of fibrinogen
      420.
AB  - In addition to the conventional fibrinogen with its alpha, beta, and gamma
      subunit chains, there is a subclass of fibrinogen molecules, accounting for one
      percent of the total in human adults, in which both alpha chains have been
      replaced by extended alpha chains (alpha E) that sport a globular C-terminal
      domain (alpha EC) comparable to beta C and gamma C. Using nomenclature based on
      molecular weight, the subclass of alpha E-containing molecules has been named
      fibrinogen-420 to differentiate it from the better known fibrinogen, now referred
      to as fibrinogen-340. Review of the events leading to the discovery of fibrinogen
      420 in the early 1990s and its subsequent characterization, culminating in the
      crystal structure of its unique alpha EC domains, highlights special aspects of
      its evolutionary history, outstanding features of its structure, and the
      perplexities of its biology. Various working hypotheses that have driven prior
      investigation are evaluated and practical insights are offered to spur further
      research into the role of fibrinogen-420.

PMID- 11460499
TI  - Mutations on fibrinogen (gamma 316-322) are associated with reduction in platelet
      adhesion under flow conditions.
AB  - In this paper we report on studies of platelet adhesion to several fibrinogen
      gamma chain variants under physiological flow conditions. Reduced platelet
      adhesion was found to patient dysfibrinogen Vlissingen and its recombinant form
      (deletion of gamma 319-320). Furthermore, substitutions of the amino acids 318,
      320, or both in the recombinant fibrinogen gamma chain showed a strong decrease
      in platelet adhesion under flow conditions in our perfusion system. Antibodies
      raised against peptides covering these sequences inhibited platelet adhesion
      completely, which suggested that the gamma 316-322 sequence could be involved in
      platelet adhesion in flowing blood.

PMID- 11460500
TI  - A new model for in vitro clot formation that considers the mode of the
      fibrin(ogen) contacts to platelets and the arrangement of the platelet
      cytoskeleton.
AB  - The constitution of platelet-fibrin(ogen) contacts, the separation of the
      platelets initially aggregated, and the rearrangement of the platelet
      cytoskeleton during clot formation (0.5 to 60 minutes after thrombin stimulation)
      were investigated using ultrastructural and immunocytochemical techniques. After
      aggregation, fibrin polymerizing within focal contacts and from degranulating
      secretory granules contributed to the fibers. The initially formed focal contacts
      with fibrin obviously persisted during clot formation. The physiological
      branching of the fibers enabled separation of platelets. The contact associated
      cytoskeleton formed a constricting and fiber internalizing sphere, but later
      stress fiber like bundles. As retraction progressed, the cytoskeleton changed to
      stress fiber connecting focal contacts with fibers. A model of clot formation in
      vitro is presented that reflects both the contributions of platelets (fibrin
      fiber internalization and retraction) and of fibers (branching) enabling the
      retraction.

PMID- 11460501
TI  - Mutation of W215 compromises thrombin cleavage of fibrinogen, but not of PAR1 or
      protein C.
AB  - W215 is a highly conserved residue that shapes the S3 and S4 specificity sites of
      thrombin. Replacement of W215 with Phe produces modest effects on thrombin
      function, whereas the W215Y replacement significantly compromises the amidolytic
      activity toward synthetic and natural substrates. Replacement of W215 with Ala
      reduces fibrinogen and PAR4 cleavage 500-fold and 280-fold, respectively. On the
      other hand, the mutant decreases protein C activation and PAR1 cleavage only
      threefold and 25-fold, respectively. The W215A mutant cleaves PAR1 with a
      specificity constant more than 13-fold greater than that of fibrinogen and
      protein C, and 800-fold greater than PAR4. This is the first thrombin derivative
      to be described that functions as an almost exclusive activator of PAR1. The
      environment of W215 influences differentially three physiologically important
      interactions of thrombin, a feature that should assist in the separate study of
      each of these functions in vivo.

PMID- 11460502
TI  - Platelets in suspension require preactivation to adhere to immobilized
      fibrinogen.
AB  - Previous studies using whole blood perfusion through flow chambers have suggested
      that unactivated platelets can adhere to surface immobilized fibrinogen (Fg).
      However, the red blood cells needed for surface delivery of the platelets may
      activate platelets by released adenosine diphosphate (ADP). Our studies of
      coaggregation of unactivated or ADP-activated platelets with Fg-coated latex
      beads in flowing suspensions show that only preactivated platelets can adhere to
      Fg-coated surfaces.

PMID- 11460503
TI  - Platelet adhesion to fibrinogen coated at various densities.
AB  - Platelet adhesion to low-density coated fibrinogen induces greater protein
      tyrosine phosphorylation of SYK and FAK than adhesion to high-density coated
      fibrinogen, and leads to activation of integrin alpha IIb beta 3 on the luminal
      side of adherent platelets.

PMID- 11460504
TI  - Attenuation of neointima formation following arterial injury in PAI-1 deficient
      mice.
AB  - Atherosclerosis is a chronic inflammatory disease in which the fibrinolytic
      system has been implicated as playing a major role. In order to directly assess
      the physiological impact an imbalanced fibrinolytic system has on both early and
      late stages of this disease, mice deficient for PAI-1 (PAI-1-/-) were used in a
      model of vascular injury/repair and compared to wildtype mice (WT). Copper
      containing cuffs were placed around the carotid arteries of these mice and the
      injured arteries were removed at either 7 or 21 days for histological analyses.
      At both times after injury, fibrin was prevalent in WT arteries, whereas only
      diffuse in PAI-1-/- arteries. At 21 days after injury, a prominent, multilayered
      neointima was evident in WT arteries, with no evidence of a neointima in PAI-1-/-
      arteries. Results from this study directly confirm the involvement of the
      fibrinolytic system in vascular repair processes following injury and indicate
      that fibrin could potentially play a role in lesion formation by stimulating
      smooth muscle cell proliferation, collagen synthesis, and intracellular
      cholesterol accumulation.

PMID- 11460505
TI  - Transcriptional control mechanism of fibrinogen gene expression.
AB  - Although fibrinogen genes are expressed constitutively in hepatocytes, their
      transcription can be greatly increased during inflammatory stress. Extensive
      studies have focused on the cytokine mediated transcriptional regulation of
      fibrinogen genes. It is clear that interleukin-6 (IL-6) and its family of
      cytokines are the major inducers of fibrinogen gene expression. Functional
      analyses of all three fibrinogen promoters for human and rat all demonstrate that
      the conserved CTGGGAA motifs within the proximal promoter of each fibrinogen gene
      are the IL-6 responsive elements. Exploration of the rat gamma fibrinogen gene
      demonstrated that the IL-6 activated transcription factor, STAT3, binds to the
      CTGGGAA motif and is required for the IL-6 mediated upregulation of this gene. IL
      6 mediated fibrinogen production can be significantly elevated by glucocorticoid
      treatment. The synergistic effect of glucocorticoids and IL-6 relies on the
      functional interaction between STAT3 and glucocorticoid receptor. In addition to
      the upregulation signals for fibrinogen gene expression during inflammatory
      stress, other signaling also downregulates the expression of fibrinogen genes.
      For example, the proinflammatory cytokine IL-1 beta exerts inhibitory function on
      IL-6 mediated fibrinogen gene expression. Given the fact that elevated levels of
      fibrinogen in blood correlate with increased risk for cardiovascular disease,
      there is strong motivation to explore the molecular mechanisms that control
      fibrinogen expression, especially those signals that may downmodulate expression
      and thus provide novel approaches to controlling fibrinogen levels.

PMID- 11460506
TI  - Fibrinogen biosynthesis. Assembly, intracellular degradation, and association
      with lipid synthesis and secretion.
AB  - Plasma fibrinogen is synthesized primarily in hepatocytes and assembly of the
      three component chains (A alpha, B beta, and gamma) into its final form as a six
      chain dimer (A alpha, B beta, gamma)2 occurs rapidly in the lumen of the
      endoplasmic reticulum (ER). Assembly takes place in a stepwise manner with single
      chains interacting with each other to form A alpha-gamma and B beta-gamma
      complexes. The two-chain complexes then acquire another chain to form half
      molecules (A alpha, B beta, gamma)1, which in a final step are linked to form the
      six-chain (A alpha, B beta, gamma)2 complex. As with other secreted
      glycoproteins, N-linked glycosylation of B beta and gamma chains commences in the
      ER and is completed in Golgi organelles. Sulfation and phosphorylation occur at
      post-ER stages of the secretory process. Since some ER chaperones coisolate with
      nascent fibrinogen chains they have been implicated in assisting chain assembly.
      Studies with recombinant systems, using deletion and substitution mutants,
      indicate that initial chain assembly depends on hydrophobic interactions present
      in the C-terminal half of the coil-coil domains and that inter- and intra
      disulfide bonds that stabilize fibrinogen are needed to complete chain assembly.
      Not all the chains that are synthesized are assembled into fibrinogen and the
      unassembled chains are not secreted. HepG2 cells contain surplus A alpha and
      gamma chains that accumulate as free gamma chains and as an A alpha-gamma
      complex. A alpha-gamma is degraded by lysosomes whereas the gamma chain is
      degraded by the proteasome-ubiquitin system. Studies with expression of single
      chains by COS cells confirm that gamma and B beta are hydrolyzed by proteasomes
      and indicate that A alpha is degraded partially both by lysosomes and
      proteasomes. The role of surplus chains in regulating fibrinogen assembly is not
      understood but overexpression of any one chain, elicited by transfection of HepG2
      cells, results in the upregulation of the other two genes, increased fibrinogen
      synthesis and secretion, and maintenance of surplus intracellular A alpha and
      gamma chains. HepG2 cells, programmed in this manner to increase basal fibrinogen
      expression, have higher HMG-CoA reductase mRNA levels, enhanced cholesterol and
      cholesterol ester synthesis, and increased secretion of apolipoprotein B (apoB).
      Overexpression of basal levels of fibrinogen does not affect synthesis of other
      acute phase proteins. Enhanced secretion of apoB is due to diminished degradation
      of nascent apoB by proteasomes and not to increased expression. Increased
      secretion of apoB is associated with increased basal expression of fibrinogen and
      is not affected when fibrinogen expression is stimulated by interleukin-6. In
      HepG2 cells, a feedback mechanism exists and extracellular sterols specifically
      downregulate expression of the three fibrinogen genes. These studies link, at the
      cellular level, basal fibrinogen expression with lipid metabolism.

PMID- 11460507
TI  - Fibrinogen gene mutations accounting for congenital afibrinogenemia.
AB  - This article reviews recent progress made in understanding the molecular basis of
      congenital afibrinogenemia, an autosomal recessive coagulation disorder
      characterized by the complete absence of detectable fibrinogen. We have
      identified the first causative mutations for this disorder in a non
      consanguineous Swiss family; these were homozygous deletions of approximately 11
      kb of the fibrinogen alpha chain (FGA) gene. Haplotype data implied that the
      deletions occurred on distinct ancestral chromosomes, suggesting that this region
      may be susceptible to deletion by a common mechanism. All the deletions were
      identical to the base pair, and probably resulted from non-homologous
      (illegitimate) recombination. In a subsequent study of 13 unrelated patients with
      congenital afibrinogenemia we analyzed the FGA gene in order to identify the
      causative mutations, and to determine the prevalence of the 11-kb FGA deletion.
      Although this deletion was found in an additional unrelated patient, the most
      common mutation was at the donor splice site of FGA intron 4 (IVS4 + 1 G > T).
      Three frameshift mutations, two nonsense mutations, and one other splice site
      mutation were also characterized. Other studies identified one further FGA
      nonsense mutation, two FGB missense mutations, and one FGG nonsense mutation, all
      in homozygosity in a single patient. In conclusion, the majority of patients have
      truncating mutations in the FGA gene although, intuitively, all three fibrinogen
      genes could be predicted to be equally implicated. These results will facilitate
      molecular diagnosis of the disorder, permit prenatal diagnosis for families who
      so desire, and pave the way for new therapeutic approaches such as gene therapy.

PMID- 11460508
TI  - Effects of diet, drugs, and genes on plasma fibrinogen levels.
AB  - Plasma levels of fibrinogen have been identified as independent risk predictors
      of cardiovascular disease. This has greatly increased interest in the regulation
      of plasma fibrinogen levels. Many demographic and environmental factors are known
      to affect fibrinogen levels, such as diet, use of several drugs, age, smoking,
      body mass, gender, physical exercise, race, and season. Additionally, it is also
      known that genetic factors determine the fibrinogen levels, and also that they
      determine the response of fibrinogen levels to environmental factors. Estimates,
      based on twin studies, suggest that 30-50% of the plasma fibrinogen level is
      genetically determined. The effect of dietary components on plasma fibrinogen
      levels is modest. Several components have been identified as factors that
      influence fibrinogen levels. Among those are fish oil, other lipids, and fibers.
      Dietary components that were expected to have an effect on fibrinogen, but for
      which no association was observed are black and green tea. Several drugs are
      known to influence fibrinogen levels, the most studied of which are platelet
      aggregation inhibiting drugs, such as ticlopidine, and the lipid lowering fibric
      acid derivatives (fibrates). Both types of drugs decreased the plasma fibrinogen
      level by about 10%, and bezafibrate lowers fibrinogen even more in patients with
      diabetes. No clear effect was observed for the HMG-CoA reductase inhibitors
      (statins). In the Bezalip study, fibrinogen levels decreased in patients treated
      with bezafibrate, but this had no clear effect on the risk of cardiovascular
      disease. This suggests that several mechanisms influence the fibrinogen level and
      that these mechanisms may contribute differently to cardiovascular disease.
      Several variations in the fibrinogen genes have been described and especially
      variations in the promoter region of the fibrinogen beta-gene are interesting,
      because the synthesis of the fibrinogen B beta chain is considered to be the rate
      limiting step in the fibrinogen biosynthesis. In many studies the fibrinogen beta
      gene polymorphisms (-455G/A, -148C/T, and BclI) are found to be associated with
      the plasma levels of fibrinogen. However, they are not associated with the risk
      of cardiovascular events, although in several studies an association with the
      severity and progression of atherosclerosis has been reported. It has also been
      observed frequently that the fibrinogen beta-gene promoter polymorphisms are
      associated with the response of fibrinogen levels to environmental factors, such
      as exercise and trauma. In conclusion, plasma fibrinogen levels are regulated by
      an interesting and complex interplay between environmental and genetic factors.

PMID- 11460509
TI  - Genetic and immunological characterization of fibrinogen inclusion bodies in
      patients with hepatic fibrinogen storage and liver disease.
AB  - Fibrinogen storage in liver cells can occur under three different morphological
      inclusions. Type I contain all three fibrinogen chains (A alpha, B beta, and
      gamma) as well as D and E fragments, whereas type II and III lack B beta as well
      as D and E fragments. Patients with type I inclusions carry a point mutation
      (gamma 284 Gly-Arg). The mutation is not present in patients with type II and III
      inclusions. These results appear to suggest that the three various phenotypic
      expressions (i.e., morphological variants) reflect different genetical
      abnormalities of fibrinogen.

PMID- 11460510
TI  - Hypofibrinogenemia associated with a heterozygous C-->T nucleotide substitution
      at position -1138 BP of the 5'-flanking region of the fibrinogen A alpha-chain
      gene.
AB  - We found a novel genetic abnormality, heterozygous C-->T nucleotide substitution
      at position -1138 bp in the 5'-flanking region of the fibrinogen A alpha gene, in
      patients with hypofibrinogenemia. Luciferase reporter assay using the pGL3-basic
      vector and CHO cells indicates that the transcriptional activity of a vector
      incorporated with -1138T was reduced to one-third that of a vector incorporated
      with -1138C. These results suggest that the region adjacent to the -1138C bp of
      the 5'-flanking region of the fibrinogen A alpha gene is one of the most crucial
      sites for the transcription of the fibrinogen A alpha gene.

PMID- 11460511
TI  - Modified clotting properties of fibrinogen in the presence of acetylsalicylic
      acid in a purified system.
AB  - To assess how treatment with acetylsalicylic acid (ASA) alters the fibrin network
      structure, clotting was initiated in purified fibrinogen incubated with ASA by
      adding thrombin. Clotting time and maximum absorbance of the fibrin aggregation
      curve were used to demonstrate the potential of fibrin generation. The results
      showed that the clotting properties of fibrinogen decreased and that the affinity
      of plasminogen to fibrin or thrombin inhibition by antithrombin increased if
      plasminogen or antithrombin, respectively, were present in the reaction system.
      The effect of ASA varied in a dose dependent manner. It was concluded that ASA
      may directly or indirectly confer positive or negative effects on the stability
      of the fibrin clot and that the balance between these effects may be regulated by
      the ASA dose.

PMID- 11460512
TI  - Identification and characterization of five new fibrinogen gene polymorphisms.
AB  - It is clear that plasma fibrinogen levels are strongly influenced by genetic
      factors. To date 14 polymorphic sites have been identified within the fibrinogen
      gene cluster, mainly by restriction fragment length polymorphism (RFLP) and
      single-stranded conformation polymorphism (SSCP) analyses. Since elevated plasma
      fibrinogen is an independent risk factor for cardiovascular disease, these and
      other polymorphisms are of practical interest in defining haplotypes that
      correlate with fibrinogen levels. Here, DNA sequencing of fibrinogen genes from
      four patients led to the identification of 17 variations from the published
      sequence. Nine of these occurred in all chromosomes sequenced and were considered
      to be errors in the published data. Of the remaining eight, five represented
      novel variations, three having been previously described. The population
      frequency of the five novel variations, together with six known polymorphisms,
      was estimated by genotyping 50 normal individuals at each locus. The five new
      variations were all found at polymorphic frequencies in this group. Two of these
      new polymorphisms, B beta intron 2 and B beta codon 159, belong to the B beta
      linkage group defined by Behague et al., since their rare alleles occurred in
      complete concordance with the rare alleles of B beta Mnl I and B beta Bcl I.
      Calculation of pairwise linkage disequilibrium coefficients showed that the three
      remaining novel polymorphisms, A alpha Dde I, B beta Hinf I, and gamma intron 9
      exhibited linkage equilibrium with respect to all other loci examined, including
      nearby polymorphisms that are themselves in strong linkage disequilibrium. This
      data indicates that these polymorphisms occur randomly with respect to background
      haplotype, and suggests that they are mutational hot spots.

PMID- 11460513
TI  - Development of pulmonary fibrosis in fibrinogen-deficient mice.
AB  - Bleomycin is an antineoplastic drug commonly used for the treatment of many
      carcinomas and lymphomas. Its toxic side effect on lung tissue is a major
      limitation to its use, with approximately 3-5% of patients affected. Although the
      number of affected patients is small, the damage incurred by bleomycin in these
      patients is often irreversible and, at times, fatal. A number of therapies have
      been shown to be effective in animal studies to minimize damage, but to date no
      "magic bullet" has been identified. Many proteins of the fibrinolytic system have
      been implicated as playing a role in the progression of the disease, one of which
      is fibrinogen (Fg) acting in the context of a fibroproliferative agent. Its
      presence correlates with an upregulation of plasminogen activator inhibitor-1 and
      tissue factor in alveolar cells surrounding the lesion area. It is believed that
      Fg participates in the activation and migration of fibroblasts and provides a
      scaffold, in the form of fibrin, for cell migration following induction of acute
      lung injury. To further understand the mechanism of injury following bleomycin
      treatment and the possible role of fibrinogen therein, mice have been generated
      with a targeted deletion of the gamma-chain of Fg, which resulted in the absence
      of detectable circulating Fg. The offsprings of Fg heterozygous mice (FG+/-) mice
      follow Mendelian distributions indicating no embryonic lethality with this
      deletion. Approximately one-half of the Fg-deficient (FG-/-) neonates exhibited
      bleeding episodes, approximately one-half of which were fatal. For the pulmonary
      fibrosis study, FG-/- mice and wildtype littermates were administered a bleomycin
      solution intratracheally and the disease was allowed to progress for two weeks.
      The mice were then sacrificed, the left lung was excised for hydroxyproline
      analysis, the right lung was processed for histologic profiling. Examination of
      trichrome stained sections, surprisingly, revealed no qualitative difference
      between wildtype and FG-/- animals. The extent and pattern of the deposition of
      collagen were also similar. These results were quantitatively confirmed by
      hydroxyproline analysis, which revealed equivalent increases in collagen content
      between wildtype and FG-/- animals when compared to appropriate saline controls.
      Analysis of the early acute inflammatory stage of the disease showed a difference
      in the neutrophil population between days three and five of the disease. These
      studies suggest that, although fibrinogen is not required for collagen deposition
      at the later stage of the disease, it may play a role in the early acute
      inflammation stage.

PMID- 11460514
TI  - Fibrinogen polymorphisms and atherothrombotic disease.
AB  - Common polymorphisms of the fibrinogen gene cluster are associated with
      circulating fibrinogen level and with susceptibility to and/or severity of
      atherothrombotic disease. The frequencies of the polymorphisms vary among
      different ethnic groups but there is strong linkage disequilibrium at the beta
      fibrinogen gene locus so that, in caucasian populations, there are only four
      common beta-fibrinogen haplotypes. One of these haplotypes, defined by the beta
      fibrinogen -455A allele, is associated with elevated fibrinogen level and
      increased risk of atherothrombotic disease. The molecular mechanism of these
      associations is currently under investigation.

PMID- 11460515
TI  - Fibrinogen and its degradation products as thrombotic risk factors.
AB  - Recent meta-analyses of prospective studies have shown that plasma levels of both
      fibrinogen and fibrin D-dimer are independent predictors of ischemic heart
      disease. Although at present reported studies using different assays do not show
      heterogeneity, there is a need for prospective comparison of different assays, as
      well as for development of standards. Collaborative development of the clinical
      use of these risk predictors is also required. Finally, the causal significance
      of the associations of fibrinogen and D-dimer with thrombotic events remains to
      be established by randomized controlled trials of reduction in their plasma
      levels.

PMID- 11460516
TI  - Wound healing. Role of commercial fibrin sealants.
AB  - This paper focuses on the use of commercial fibrin sealant (FS) in specific wound
      healing applications. This review is not intended to be all inclusive, but to
      examine in vitro and in vivo models, as well as select clinical conditions that
      are representative of specific wound healing applications of FS.

PMID- 11460517
TI  - Fibrinogen non-inherited heterogeneity and its relationship to function in health
      and disease.
AB  - In healthy individuals fibrinogen occurs in more than one million non-identical
      forms because of the many possible combinations of biosynthetically or
      postbiosynthetically modified or genetically polymorphic sites. The various forms
      may show considerable differences in their functional properties. Normal variant
      sites are due to alternative splicing, modification of certain amino acid
      residues, and proteolysis. Both the A alpha and the gamma chain occur in two
      splice forms, and it is known that only the shorter gamma chain can interact with
      platelets, but the longer may bind thrombin and factor XIII. Many types of
      posttranslationally modified amino acid residues are present in fibrinogen. The A
      alpha chain is partially phosphorylated at two sites, possibly leading to
      protection against proteolysis. The B beta chain is N-glycosylated and partially
      proline hydroxylated, each at one site. The gamma chain is N-glycosylated at one
      site and the longer splice form doubly tyrosine-sulfated. The glycosylations are
      believed to protect against polymerization and proteolysis. All three chains are
      partially oxidized at methionine residues and deamidated at asparagine and
      glutamine residues. The A alpha and gamma chain are partially carboxy-terminally
      degraded by proteolysis, the shorter forms causing a decrease in polymerization,
      crosslinking, and clot stability. Abnormal variants occur in patients with
      diabetes mellitus, in the form of glycated lysine residues; in patients with
      certain types of cancer, in the form of crosslinked degradation products; in
      patients with certain types of autoimmune disease, in the form of complexes with
      antibodies; in cigarette smokers; and in individuals treated with acetylsalicylic
      acid, in the form of acetylated lysine residues.

PMID- 11460518
TI  - Fibrin degradation products. A review of structures found in vitro and in vivo.
AB  - This review attempts to relate subunit structures of fibrin degradation products
      (FnDP) made in vitro with structures found in vivo. The domainally directed
      fragmentation in vitro of both fibrinogen and fibrin is emphasized, all fragments
      being various associations of the two core fibrin fragments D and E. The
      digestion of fibrinogen by plasmin in vivo is rare, and the crosslinking of
      fibrin in vivo takes place at a very early stage in the clotting/polymerization
      process. The notion that as fibrin forms in vivo it orchestrates its own
      destruction is developed. Plasmas from patients suffering from disseminated
      intravascular coagulation demonstrate very large crosslinked FnDP fragments in
      their plasmas which seem to contain not alone fibrinopeptide A but also subunits
      with intact alpha chains. This is interpreted to mean that many of the large
      soluble fragments found in vivo, and heretofore known as FnDP, are in reality
      long fibrin polymers, random parts of whose structures have been converted to
      FnDP by lysis of the carboxy terminal regions of the alpha chains in the polymer.
      The ratio of intact fibrin to FnDP in these large soluble structures may be a
      useful clinical marker; however, such data can only be relied upon when blood
      samples are taken into an anticoagulant mix that contains a fibrinolytic
      inhibitor. Some of the biological effects of FnDP structures in vivo (fibrinogen
      synthesis, vasoactivity) are still quite ambiguous.

PMID- 11460519
TI  - Antifibrinogen IgG, fibrinogen, and Clq complexes circulating in a
      hypodysfibrinogenemic proband. Isolation, stoichiometry, and partial
      characterization.
AB  - Circulating antifibrinogen antibodies have been reported in rare afibrinogenemic
      propositi, apparently occurring following fibrinogen replacement therapy, but
      immune complexes have not been described. In this report we describe circulating
      immune complexes formed by a monoclonal antifibrinogen IgG in a heterozygous
      hypodysfibrinogenemic (A alpha 16 Arg-->Cys) proband. Estimated by partial
      protein sequence and by other analyses, each immune complex consisted of one
      fibrin(ogen), one C1q, and 3-4 IgG molecules. The complexes were
      cryoprecipitable, a property also displayed by mixtures of proband IgG and normal
      fibrinogen. Indicating that both D and E domains were necessary for this
      behavior, cryoprecipitability was abolished by preincubation of the isolated IgG
      with either isolated normal fibrinogen fragment D100 or E. Consistent with the
      crossreactivity of the IgG with normal and mutant fibrinogen, the results suggest
      that the primary epitope resides on a D-E locus on the fibrin polymer formed by
      normal and abnormal molecules containing the uncleaved (or mutant) peptide A.

PMID- 11460520
TI  - Factor XIII prevents development of myocardial edema in children undergoing
      surgery for congenital heart disease.
AB  - In a prospective investigation of perioperative cardiac edema formation requiring
      a delayed sternal closure, we identified thrombin increase combined with a
      simultaneous decrease of factor XIII as a probable cause. After experimental
      studies additionally revealed that factor XIII could protect endothelial barrier
      function, we did another prospective randomized trial in which factor XIII or
      placebo was preoperatively substituted. The substitution finally showed distinct
      effects minimizing the incidence of myocardial swelling. Therefore, the clinical
      application of factor XIII may have a valuable therapeutic benefit in cases of
      leakage syndrome during extracorporeal circulation in congenital heart surgery.

PMID- 11460521
TI  - Fibrinogen: a vascular risk factor, why? Contributing effect of oncostatin M on
      both fibrinogen biosynthesis by hepatocytes and participation in atherothrombotic
      risk related to modifications of endothelial cells.
AB  - Fibrinogen is a vascular risk factor. We suggest that it is a marker of cytokine
      secretion that simultaneously stimulates fibrinogen biosynthesis and vascular
      modifications responsible for atherothrombosis. Among these cytokines, oncostatin
      M (OSM) is the most potent cytokine for inducing fibrinogen biosynthesis by
      hepatocytes, and it could contribute to endothelial cell anomalies involved in
      the atherothrombotic process. Here we show that OSM acts (1) by inducing the
      secretion involved in invasion of the vessel wall by monocytes; (2) by inducing
      angiogenesis it promotes plaque destabilization, rupture, and consequently
      thrombosis; and (3) by decreasing fibrinolysis on macrovascular endothelial
      cells.

PMID- 11460522
TI  - Purification of fibrinogen and virus removal using preparative electrophoresis.
AB  - The Gradiflow is a novel, scalable preparative electrophoresis technique that
      uses the dual characteristics of size and charge to isolate target macro- and
      micromolecules from complex biological solutions. It does this with high
      resolution and in rapid time. The mild buffers are used to assist in retaining
      biological activity of the isolated protein. Gradiflow technology employs a
      sandwich of three polyacrylamide membranes configured to allow passage of
      macromolecules ranging in size from 10 kDa to 1,500 kDa. Fibrinogen was isolated
      from cryoprecipitate 1 using a single phase process. This separation was achieved
      within three hours with yields of 85%. Purified fibrinogen was then characterized
      using biophysical characterization of fibrin clot structure and compared with
      clots derived from a commercially available product and human plasma.
      Significantly, clots developed from Gradiflow fibrinogen had characteristics
      closer to human plasma. Viral removal characteristics of the Gradiflow were
      investigated by spiking the source material (cryoprecipitate 1) with canine
      parvovirus and testing for its presence in the isolated fibrinogen using PCR.
      Parvo removal was found to be greater than 4 logs and was achieved during the
      purification process. The Gradiflow offers the advantage of large-scale
      separation of macromolecules and provides a new approach to fibrinogen separation
      that is quite distinct from other present-day technologies. The technology is
      capable of isolating protein with high purity, recovery, and functionality in
      combination with the removal of viruses during the purification. Furthermore, it
      is capable of integrating into present production systems, significantly
      improving yield and functionality of target molecules.

PMID- 11460523
TI  - Effect of moderate alcohol consumption on fibrinogen levels in healthy volunteers
      is discordant with effects on C-reactive protein.
AB  - In a diet-controlled, crossover trial with 10 middle-aged men and 9
      postmenopausal women, baseline concentrations of fibrinogen influenced the
      magnitude of decrease of fibrinogen after moderate alcohol consumption. The
      mechanism of reduction is specific for fibrinogen and unrelated to a reduction in
      C-reactive protein.

PMID- 11460524
TI  - Fibrin network structure. Changes in characteristics in response to physical
      activity in combination with a pre-exercise meal.
AB  - The metabolic environment determines the characteristics of fibrin network
      structure (FNS) in plasma. Physical activity or changes in the diet (e.g., high
      and low glycemic index meals) can initiate these changes. The FNS were measured
      by means of mass-length ratio, turbidity, and compaction of the plasma obtained
      from male subjects. Samples were taken before and after the introduction of the
      different diets and physical activity. The results indicate that changes in the
      FNS do occur, but further investigation is required to obtain conclusive results.

PMID- 11460525
TI  - Influence of plasma triglyceride and plasma cholesterol levels on the clearance
      rate of fibrinogen.
AB  - Increased plasma levels of fibrinogen are associated with a higher risk of
      cardiovascular disease. It has been suggested that lipid levels may influence the
      fibrinogen levels by a mechanism other than the synthesis rate, for example a
      decreased clearance rate. We performed a pilot study to explore this possibility.
      Twelve male Wistar rats were fed for four weeks with a control low fat/low
      cholesterol diet, a high fat/high cholesterol diet, and a high fat/high
      cholesterol diet with an additional 0.5% cholic acid. Labeled 125I fibrinogen was
      injected, and blood was sampled repeatedly. From the plasma radioactivity of the
      samples, fibrinogen halflife time was calculated for each animal. Our results
      suggest that plasma lipids lengthen the fibrinogen halflife times, although the
      differences were not statistically significant in this small study. Our final
      conclusion from this study is that lipids may have an effect on the turnover rate
      of fibrinogen and possibly affect fibrinogen levels through this mechanism.

PMID- 11460526
TI  - Hereditary disorders of fibrinogen.
AB  - Fibrinogen, a 340-kDa plasma protein, is composed of two identical molecular
      halves each consisting of three non-identical A alpha-, B beta- and gamma-chain
      subunits held together by multiple disulfide bonds. Fibrinogen is shown to have a
      trinodular structure; that is, one central nodule, the E domain, and two
      identical outer nodules, the D-domains, linked by two coiled-coil regions. After
      activation with thrombin, a pair of binding sites comprising Gly-Pro-Arg is
      exposed in the central nodule and combines with its complementary binding site a
      in the outer nodule of another molecules. By using crystallographic analysis, the
      alpha-amino group of alpha Gly-1 is shown to be juxtaposed between gamma Asp-364
      and gamma Asp-330, and guanidino group of alpha Arg-3 between the carboxyl group
      of gamma Asp-364 and gamma Gln-329 in the a site. Half molecule-staggered, double
      stranded protofibrils are thus formed. Upon abutment of two adjacent D domains on
      the same strand, D-D self association takes place involving Arg-275, Tyr-280, and
      Ser-300 of the gamma-chain on the surface of the abutting two D domains.
      Thereafter, carboxyl-terminal regions of the alpha-chains are untethered and
      interact with those of other protofibrils leading to the formation of thick
      fibrin bundles and networks. Although many enigmas still remain concerning the
      exact mechanisms of these molecular interactions, fibrin assembly proceeds in a
      highly ordered fashion. In this review, these molecular interactions of
      fibrinogen and fibrin are discussed on the basis of the data provided by
      hereditary dysfibrinogens on introducing representative molecules at each step of
      fibrin clot formation.

PMID- 11460527
TI  - A database for human fibrinogen variants.
AB  - Identifying and studying abnormal human fibrinogens is a source of much
      information, and helps in taking care of the affected patients. To permit
      exhaustive numbering and easy updates, an extensive register has been compiled
      and made available on the internet. Known molecular abnormalities are mentioned
      with the essential clinical features.

PMID- 11460528
TI  - Molecular mechanisms of hypo- and afibrinogenemia.
AB  - Point mutations responsible for hypo- and afibrinogenemia are yielding new
      insights into amino acid side chains involved in the molecular processing,
      assembly, secretion, and domain stability of fibrinogen. Reverse phase
      chromatography, isoelectric focussing, electrospray mass spectrometry, and
      tryptic peptide mass mapping have shown that chains with heterozygous mutations
      of gamma 284 Gly-->Arg, B beta 316 Asp-->Tyr and gamma 371 Thr-->Ile are absent
      from plasma fibrinogen. The nonexpression of these mutations appears to result
      from perturbation of the five-stranded beta sheet of the D domain. We propose
      that this is due to retention of the variant in the endoplasmic reticulum and
      that in turn this leads to hypofibrinogenemia. Other mutations effect
      intracellular proteolysis and chain assembly. For example the mutation, A alpha
      20 Val-->Asp, makes the protein a substrate for furin, which removes the first 19
      residues of the A alpha chain as the mature molecule transits the trans golgi
      complex. Transient expression of gamma 153 Cys-->Arg chains together with A alpha
      and B beta chains suggests this mutation might perturb chain assembly, and the
      incorporation of mutations of B beta 353 Leu-->Arg or B beta 400 Gly-->Asp into
      intracellular fibrinogen precludes its subsequent export from host cells
      expressing fibrinogen genes. The graded severity of the hypo- and
      afibrinogenemias associated with homozygous A alpha chain truncations suggest the
      absolute minimal requirement for molecular assembly is the formation of the C
      terminal disulfide ring of the coiled coil.

PMID- 11460529
TI  - Effect of fluoride anions on gramicidin photoinactivation sensitized by
      sulfonated aluminum phthalocyanines.
AB  - Interaction of potent photodynamic agents, sulfonated aluminum phthalocyanines
      (AlPcSn where n is a number of sulfonic groups), with biological membranes was
      studied here using model systems: sensitized photoinactivation of gramicidin
      channels in planar lipid bilayers and adsorption on lipid monolayers. Fluoride
      anions known to form complexes with aluminum were found to inhibit both the
      adsorption of aluminum phthalocyanines on lipid monolayers, as measured with a
      Langmuir trough by surface pressure and surface potential changes, and
      photodynamic efficacy of the dyes, as studied by gramicidin channel
      photoinactivation. The similar effects were caused by the alkalinization of the
      medium. Fluoride anions appeared to be much more effective in the case of AlPcS4
      as compared to AlPcS3. The suppression of the photodynamic potency of aluminum
      phthalocyanines was attributed to desorption of the dyes from lipid bilayers
      induced by fluoride or hydroxyl ions. With AlPcS4 an enhancement of the dye
      aggregation leading to a decrease in the sensitizing activity was probably
      involved in the fluoride effect as revealed by absorption and fluorescence
      spectral measurements. Capillary electrophoresis was employed to understand the
      mechanism of the dye desorption. The results of these experiments indicated that
      the reduction in the membrane affinity was associated with an increase in the
      negative charge of the dye molecules due to the binding of fluoride or hydroxyl
      ions.

PMID- 11460530
TI  - Light reflected from red mulch to ripening strawberries affects aroma, sugar and
      organic acid concentrations.
AB  - Strawberry (Fragaria ananassa) fruit size and flavor are important to both
      growers and consumers. Plastic mulches are frequently used in raised-bed culture
      to conserve water, control weeds with less herbicides, keep fruit clean and
      produce ripe berries earlier in the season. The most commonly used plastic mulch
      color is black. We hypothesized that changing mulch color to reflect more far-red
      (FR) and red light (R) and a higher FR/R photon ratio would keep those benefits
      and improve berry size and flavor by altering phytochrome-mediated regulation of
      pathways in ripening berries. Size and chemical composition of berries developed
      in sunlight over a specially formulated red plastic were compared with those that
      developed over standard black plastic mulch. Berries that ripened over red were
      about 20% larger, had higher sugar to organic acid ratios and emitted higher
      concentrations of favorable aroma compounds. We conclude that FR and the FR/R
      ratio in light reflected from the red mulch on the soil surface acted through the
      natural phytochrome system within the growing plants to modify gene expression
      enough to result in increased fruit size and improved concentrations of
      phytonutrient, flavor and aroma compounds.

PMID- 11460531
TI  - Ultraviolet light induces reactivation in a murine model of cutaneous herpes
      simplex virus-1 infection.
AB  - We have developed a model of cutaneous herpes simplex virus-1 (HSV-1)
      reactivation in SKH-1 hairless mice which closely mimics the condition in humans.
      Sixty plaque-forming units of HSV-1 strain 17 syn+ were applied to a
      superficially abraded area on the lateral body wall. More than 85% of mice
      developed primary HSV-1 infection characterized by a zosteriform pattern of
      cutaneous vesiculation and ulceration. Approximately one-third of mice with
      primary skin lesions succumbed to neurologic disease and in the remaining mice
      cutaneous lesions healed completely. Subsequent exposure of healed areas to two
      minimal inflammatory doses of UV resulted in recrudescence of skin lesions in the
      irradiated areas in almost 60% of mice. Lesions appeared approximately 4 days
      after irradiation, persisted for 3-5 days and then resolved completely.
      Reactivation rarely resulted in death due to neurologic disease. Primary lesions
      had a histologic appearance typical of cutaneous HSV-1 infection with vesicles
      and focal epithelial necrosis accompanied by the formation of epithelial
      syncytial cells and the presence of herpetic intranuclear inclusion bodies. In
      primary lesions HSV-1 was demonstrated by immunohistochemistry, polymerase chain
      reaction and culture. In reactivated lesions epithelial syncytia and inclusion
      bodies were not seen; however, virus was demonstrable by polymerase chain
      reaction and culture. Exposure of the uninfected side to UV did not stimulate
      disease recurrence suggesting that local effects of UV rather than systemic
      immunosuppression were responsible for reactivation. Reactivation could also be
      obtained with two minimal inflammatory doses of UV from a UV-340 light source
      which emits light approximating the solar spectrum.

PMID- 11460532
TI  - Photodynamic studies of metallo 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin:
      photochemical characterization and biological consequences in a human carcinoma
      cell line.
AB  - The photodynamic activities of the free-base 5,10,15,20-tetrakis(4
      methoxyphenyl)porphyrin (TMP) and their metal complexes with zinc(II) (ZnTMP),
      copper(II) (CuTMP) and cadmium(II) (CdTMP) have been compared in two systems:
      reverse micelle of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate/water bearing
      photooxidizable substrates and Hep-2 human larynx carcinoma cell line. The
      quantum yields of singlet molecular oxygen, O2(1 delta g), production (phi delta)
      of TMP, ZnTMP and CdTMP in tetrahydrofuran, were determined yielding values of
      0.65, 0.73 and 0.73, respectively, while O2(1 delta g) formation was not detected
      for CuTMP. In the reverse micellar system, the amino acid L-tryptophan (Trp) was
      used as biological substrate to analyze the O2(1 delta g)-mediated
      photooxidation. The observed rate constants for Trp photooxidation (kobsTrp) were
      proportional to the sensitizer quantum yield of O2(1 delta g). A value of
      approximately 2 x 10(7) s-1 M-1 was found for the second-order rate constant of
      Trp (krTry) in this system. The response of Hep-2 cells to cytotoxicity
      photoinduced by these agents in a biological medium was studied. The Hep-2
      cultures were treated with 1 microM of porphyrin for 24 h at 37 degrees C and the
      cells exposed to visible light. The cell survival at different light exposure
      levels was dependent on phi delta. Under these conditions, the cytotoxic effect
      increases in the order: Cu-TMP << TMP < ZnTMP approximately CdTMP, correlating
      with the production of O2(1 delta g). A similar behavior was observed in both the
      chemical and biological media indicating that the O2(1 delta g) mediation appears
      to be mainly responsible for the cell inactivation.

PMID- 11460533
TI  - Photoinduced electron transfer between chlorophylls (a/b) and fullerenes
      (C60/C70) studied by laser flash photolysis.
AB  - Photoinduced electron-transfer processes in the systems of chlorophylls (Chl)
      (chlorophyll-a [Chl-a] and chlorophyll-b) and fullerenes (C60/C70) in both polar
      and non-polar solvents have been investigated with nanosecond laser photolysis
      technique, observing the transient spectra in the visible/near-IR regions. By the
      excitation of Chl in benzonitrile (BN) it has been proved that electron transfer
      takes place from the triplet excited states of Chl to the ground states of
      C60/C70. By the excitation of C70 in BN electron transfer takes place from the
      ground states of Chl to the triplet excited state of C70. In both Chl the rate
      constants and quantum yields for the electron-transfer processes are as high as
      those of zinc porphyrins and zinc phthalocyanines, indicating that the long alkyl
      chains of Chl play no role in retarding the electron transfer. The rate constant
      for the electron-mediating process from the radical anion of C70 to octylviologen
      dication yielding the octylviologen radical cation was evaluated. The back
      electron-transfer process from the viologen radical cation to the radical cation
      of Chl-a takes place in a longer time-scale, indicating that a photosensitized
      electron-transfer/electron-mediating cycle is achieved.

PMID- 11460534
TI  - Radiative relaxation of Sepia eumelanin is affected by aggregation.
AB  - The steady-state and time-resolved emission properties of aqueous solutions
      containing different aggregation state distributions of eumelanin are reported.
      Excitation spectra of the size-selected samples reveal, for the first time,
      differences in absorption bands due to varying levels of aggregation. These size
      dependent absorption properties result in size-dependent emission band shapes and
      quantum yields. For all size fractions, absorption and emission overlap
      significantly. The emission yield for small eumelanin aggregates in 5.7 times
      greater than that for large eumelanin aggregates. Time-resolved population decays
      reveal that small eumelanin aggregates are responsible for long-lived emission
      dynamics (lifetimes greater than 1 ns), while large eumelanin aggregates are the
      source of short emission decay (lifetimes less than 1 ns). Polarized emission
      decays for the large and small aggregates reveal that energy transfer occurs both
      within the same and between the separate fundamental building blocks of
      eumelanin. The observed energy transfer dynamics can be accounted for using
      Forster theory.

PMID- 11460535
TI  - Optical properties and nondestructive estimation of anthocyanin content in plant
      leaves.
AB  - Absorption and reflectance spectra of maple (Acer platanoides), cotoneaster
      (Cotoneaster alaunica), dogwood (Cornus alba) and pelargonium (Pelargonium
      zonale) leaves with a wide range of pigment content and composition were studied
      in visible and near-infrared spectra in order to reveal specific anthocyanin
      (Anth) spectral features in leaves. Comparing absorption spectra of Anth
      containing and Anth-free leaves with the same chlorophyll (Chl) content,
      absorption spectra of Anth in leaves were derived. The main spectral feature of
      Anth absorption in vivo was a peak around 550 nm; the peak magnitude was closely
      related to Anth content. A quantitative nondestructive technique was developed to
      subtract Chl contribution to reflectance in this spectral region and retrieve
      Anth content from reflectance over a wide range of pigment content and
      composition. Anth reflectance index in the form ARI = (R550)-1 - (R700)-1, where
      (R550)-1 and (R700)-1 are inverse reflectances at 550 and 700 nm, respectively,
      allowed an accurate estimation of Anth accumulation, even in minute amounts, in
      intact senescing and stressed leaves.

PMID- 11460536
TI  - Resistance of a lizard (the green anole, Anolis carolinensis; Polychridae) to
      ultraviolet radiation-induced immunosuppression.
AB  - The green anole (Anolis carolinensis) is the most northerly distributed of its
      Neotropical genus. This lizard avoids a winter hibernation phase by the use of
      sun basking behaviors. Inevitably, this species is exposed to high doses of
      ambient solar ultraviolet radiation (UVR). Increases in terrestrial ultraviolet-B
      (UV-B) radiation secondary to stratospheric ozone depletion and habitat
      perturbation potentially place this species at risk of UVR-induced
      immunosuppression. Daily exposure to subinflammatory UVR (8 kJ/m2/day UV-B, 85
      kJ/m2/day ultraviolet A [UV-A]), 6 days per week for 4 weeks (total cumulative
      doses of 192 kJ/m2 UV-B, 2.04 x 10(3) kJ/m2 UV-A) did not suppress the anole's
      acute or delayed type hypersensitivity (DTH) response to horseshoe crab
      hemocyanin. In comparison with the available literature UV-B doses as low as 0.1
      and 15.9 kJ/m2 induced suppression of DTH responses in mice and humans,
      respectively. Exposure of anoles to UVR did not result in the inhibition of ex
      vivo splenocyte phagocytosis of fluorescein labeled Escherichia coli or ex vivo
      splenocyte nitric oxide production. Doses of UV-B ranging from 0.35 to 45 kJ/m2
      have been reported to suppress murine splenic/peritoneal macrophage phagocytosis
      and nitric oxide production. These preliminary studies demonstrate the resistance
      of green anoles to UVR-induced immunosuppression. Methanol extracts of anole skin
      contained two peaks in the ultraviolet wavelength range that could be indicative
      of photoprotective substances. However, the resistance of green anoles to UVR is
      probably not completely attributable to absorption by UVR photoprotective
      substances in the skin but more likely results from a combination of other
      factors including absorption by the cutis and absorption and reflectance by
      various components of the dermis.

PMID- 11460537
TI  - Single-cell gel/comet assay applied to the analysis of UV radiation-induced DNA
      damage in Rhodomonas sp. (Cryptophyta).
AB  - The single-cell gel/comet assay is an electrophoretic technique used to detect
      single-strand breaks in DNA. Damage is assessed examining individual cells under
      an epifluorescent microscope. UV-induced DNA damage consists mostly of the
      formation of pyrimidine dimers; therefore, most of the damage cannot be detected
      using a standard comet assay. The enzyme T4 endonuclease V breaks DNA strands at
      sites of pyrimidine dimers. The main objective of this work is to evaluate the
      comet assay to detect UV-induced damage in DNA after an initial treatment of
      cells with T4 endonuclease V. This work was conducted on Rhodomonas sp.
      (Cryptophyta), a marine unicellular flagellate. Cells of Rhodomonas sp. were
      exposed to 12 h visible + ultraviolet-A + ultraviolet-B (VIS + UVA + UVB) and VIS
      (control), with and without T4 endonuclease V. Cells exposed to VIS + UVA + UVB
      showed approximately 200% more damage than control if these were treated with T4
      endonuclease V. Rhodomonas sp. were exposed to 3, 6, 9 and 12 h of VIS, VIS + UVA
      and VIS + UVA + UVB. Damage induced by VIS + UVA + UVB as detected by the comet
      assay increased along with exposure time. However, damage caused by VIS and VIS +
      UVA remained relatively constant at all times. Results of this study indicate
      that the comet assay is more sensitive to UV radiation damage when used in
      conjunction with T4 endonuclease V. This modification of the comet assay can be
      used as an alternative technique to detect DNA damage in single cells caused by
      UV radiation.

PMID- 11460538
TI  - Sunscreens and UVA protection: a major issue of minor importance.
AB  - The ultraviolet A (320-400 nm) (UVA) exposure of sunscreen-protected skin depends
      not just on the absorption characteristics of the product but also on a number of
      other factors. These include the amount of sunscreen applied and how it is spread
      over the skin. The importance of the spectral absorption of a sunscreen compared
      with these other two variables in controlling cutaneous UVA exposure is examined
      here using an analysis of variance approach. The results demonstrate that by far
      the most important factor is the application of a liberal quantity of sunscreen.
      Less important is to spread it uniformly, and least important is the precise
      shape of the sunscreen-absorption spectrum, providing, of course, the spectrum
      extends into the UVA region.

PMID- 11460539
TI  - Photodynamics of the bacteriochlorophyll-carotenoid system. 1.
      Bacteriochlorophyll-photosensitized oxygenation of beta-carotene in acetone.
AB  - Carotenoids are well-known physical quenchers of chlorophyll excited states and
      reactive oxygen species both in vivo and in vitro. They may also be involved in
      chemical quenching undergoing, e.g. isomerizations or oxidations. We have found
      that beta-carotene (Car) in aerobic acetone is rapidly oxygenated under strong
      illumination with red light (lambda exc > or = 630 nm) in the presence of
      bacteriopheophytin a. At the same time the photosensitizer undergoes only slight
      (< 10%) photodegradation. By preparative high-performance liquid chromatography
      as many as seven major products of oxygen attachment to Car have been isolated.
      Their molecular masses show that Car sequentially accumulates up to six oxygen
      atoms while its C40-skeleton remains intact.

PMID- 11460540
TI  - Spectroscopic studies on self-aggregation of bacteriochlorophyll-e in nonpolar
      organic solvents: effects of stereoisomeric configuration at the 3(1)-position
      and alkyl substituents at the 8(1)-position.
AB  - Self-aggregation of naturally occurring bacteriochlorophyll (BChl)-e in nonpolar
      organic solvents was investigated by visible absorption, fluorescence emission
      and circular dichroism spectra. Cultured brown-colored photosynthetic bacteria
      have several BChl-e as light-harvesting antenna pigments. Three major BChl-e
      homologs were separated from the extracts of the culture by reverse-phase high
      performance liquid chromatography (HPLC) and characterized by 1H-NMR and fast
      atom bombardment mass spectroscopy: 8-ethyl-12-ethyl ([E,E])-, 8-propyl-12-ethyl-
      and 8-isobutyl-12-ethyl-BChl-e farnesyl esters. All the homologs consisted of a
      mixture of the 3(1)-epimers, and epimerically pure BChl-e were also given by HPLC
      separation. All the separated BChl-e epimers, the epimeric mixtures and the
      homologous mixtures formed self-aggregates in 2% dichloromethane/hexane, giving
      visible absorption spectra similar to that of the whole cells, which showed two
      peaks (or shoulders) around 430-450 and 520 nm at the Soret region as well as a
      red-shifted Qy band relative to the monomeric. The spectral properties of the
      Soret band were basically unchanged among the epimers or epimeric/homologous
      mixtures. In contrast, the Qy band of aggregates of epimeric mixtures (except
      [E,E]) and homologous mixtures red-shifted and broadened compared with the
      epimerically pure. The red-shift and broadening of the Qy band are advantageous
      for efficient energy transfer from BChl-e aggregates to BChl-a in a baseplate in
      chlorosomes because their spectral overlap increases.

PMID- 11460541
TI  - Fluorescence behavior of the pH-sensitive probe carboxy SNARF-1 in suspension of
      liposomes.
AB  - When exposed to the intracellular environment fluorescent probes sensitive to pH
      exhibit changes of photophysical characteristics as a result of an interaction of
      the dye molecule with cell constituents such as proteins, lipids or nucleic
      acids. This effect is reflected in calibration curves different from those found
      with the same dye in pure buffer solutions. To study an interaction of the probe
      5'(and 6')-carboxy-10-dimethylamino-3-hydroxy- spiro[7H-benzo[c]xanthene-7,1'(3H)
      isobenzofuran]-3'-one (carboxy SNARF-1) with membrane lipids, we measured its
      fluorescence in model systems of large unilamellar vesicles (LUV) prepared by
      extrusion. When the dye was removed from the bulk solution by gel filtration the
      relative fluorescence intensity of the lipid-bound dye form was enhanced, showing
      a strong interaction of the dye molecule with LUV membrane lipids. Surprisingly,
      the dye molecules seem to be bound predominantly to the outer surface of the
      lipid bilayer. The same situation was found with small unilamellar vesicles
      prepared by sonication. This effect makes it difficult to use carboxy SNARF-1 for
      measurements of the internal pH in suspensions of liposomes.

PMID- 11460542
TI  - Thermal and structural changes of photosynthetic reaction centers characterized
      by photoacoustic detection with a broad frequency band hydrophone.
AB  - Photoacoustic measurements using a broad frequency band hydrophone were carried
      out in photosynthetic reaction centers (RC) isolated from Rhodobacter sphaeroides
      R-26 purple bacteria. Data were extracted on enthalpy and volume changes
      accompanying the primary steps after excitation in the range of 0-500
      microseconds aimed at further characterizing the thermodynamic properties of the
      RC. Quinone titration showed that the volume contraction accompanying the
      electron transport is sensitive to the molecular species occupying the secondary
      quinone site. delta VM = 14.4, 7.7 and 4.3 cm3 molar volume contractions were
      calculated from the measured parameters for 1, 2 and 0.07 quinone/RC after light
      excitation. Comparing the enthalpy changes (delta H) to the Gibbs free energy
      data in the literature, a rather large (26%) entropic contribution to the free
      energy changes (delta G) is estimated for the P*QAQB-->P+QA-QB electron transport
      (where QA and QB represent primary and secondary quinones, respectively). This is
      in contrast to previous estimations that delta G = delta H in these processes. On
      the other hand, only a small (4%) entropic contribution to the delta G of the
      P*QAQB-->P+QAQB- process is estimated, in agreement with the literature data. Our
      results are in good agreement with the data obtained earlier (Edens et al. [2000]
      J. Am. Chem. Soc. 122, 1479-1485).

PMID- 11460543
TI  - Dose response for UV-induced immune suppression in people of color: differences
      based on erythemal reactivity rather than skin pigmentation.
AB  - Ultraviolet radiation (UVR) is known to suppress immune responses in human
      subjects. The purpose of this study was to develop dose responses across a broad
      range of skin pigmentation in order to facilitate risk assessment. UVR was
      administered using FS 20 bulbs. Skin pigmentation and UVR sensitivity were
      evaluated using Fitzpatrick classifications, minimal erythemal dose (MED), slope
      of the erythemal dose response curve (sED), baseline pigmentation and tanning
      response. To assess immune responses dinitrochlorobenzene (DNCB) was applied to
      irradiated buttock skin 72 h after irradiation. Two weeks later DNCB was applied
      to the inside upper arm. Skin thickness was measured before and after challenge.
      Dose response was modeled (to obtain a regression line) for the entire group of
      185 subjects. With the exception of sED none of the above-mentioned pigmentation
      indicators contributed significantly to variability around the regression line.
      Thus, differences in sensitivity for multiple skin types based on Fitzpatrick
      classification or MED were not observed. However, differences in immune
      sensitivity to UVR were detected between subjects with steep erythemal dose
      response curves and those with moderate or flat responses. For subjects with
      steep erythemal responses the dose calculated to suppress the immune response by
      50% was 114 mJ/cm2. This group included individuals with Fitzpatrick skin types I
      V, MED for these subjects ranged from 30 to 80 mJ/cm2. The 50% suppression dose
      for subjects with weak or no erythemal response could not be computed (the dose
      response was flat). This resistant group included subjects with skin types IV-VI
      and MED for these subjects ranged from 41 to > 105 mJ/cm2. This study provides a
      human dose response for UVR suppression of contact sensitivity that will be
      useful in risk assessment. It is the first study to provide this information
      using the FS sun lamp and is the first study to include people of color. The sED
      appears to be a new variable for identifying sensitive subjects at risk of UVR
      induced immune suppression.

PMID- 11460544
TI  - Fluorescence excitation spectroscopy for the measurement of epidermal
      proliferation.
AB  - Fluorescence excitation spectroscopy was used to assess cellular turnover in
      human skin by monitoring changes of endogenous fluorescence. Epidermal
      proliferation was induced with alpha-hydroxy acids. Commercially available
      glycolic acid creams (8 and 4% wt/wt concentration) and a vehicle cream (placebo)
      were applied in a randomized double blinded fashion on subjects' forearms, twice
      daily for 21 days. Excitation spectra were recorded (excitation 250-360 nm,
      emission 380 nm) at days 0, 1, 3, 7, 10, 11, 14, 17 and 21. The 295 nm excitation
      band (assigned to tryptophan moieties) was used in this study as a marker for
      cellular proliferation. To further reduce the day-to-day variability of the skin
      fluorescence the intensity of the 295 nm band was normalized to the 334 nm band
      (assigned to collagen crosslinks). The fluorescence emission intensity from
      placebo-treated skin remained practically unchanged over the period of the
      measurements while the fluorescence intensity measured from the glycolic acid
      treated skin increased monotonically with treatment. The rate of increase of the
      excitation intensity with treatment was found to be dose dependent. The epidermal
      295 nm band may be used as a quantitative marker to monitor the rate of
      proliferation of epidermal keratinocytes noninvasively.

PMID- 11460545
TI  - Scalar couplings across hydrogen bonds.

PMID- 11460546
TI  - On-line cell high-pressure nuclear magnetic resonance technique: application to
      protein studies.

PMID- 11460547
TI  - Maximum entropy reconstruction, spectrum analysis and deconvolution in
      multidimensional nuclear magnetic resonance.

PMID- 11460548
TI  - Magnetic relaxation dispersion studies of biomolecular solutions.
AB  - Although the MRD method has a long record in biomolecular systems, it has
      undergone a renaissance in the past few years as methodological developments have
      provided access to new types of information. In particular, MRD studies of
      quadrupolar nuclei such as 17O and 23Na have yielded valuable insights about the
      interactions of proteins and oligonucleotides with their solvent environment. The
      biomolecular MRD literature is still dominated by hydration studies, but the
      method has also been used to study the interaction of organic cosolvents and
      inorganic counterions with biomolecules. The MRD method can potentially make
      important contributions to the understanding of the mechanisms whereby protein
      conformational stability is affected by nonaqueous solvent components, such as
      denaturants, stabilizers, and helix promoters. Residence times of water molecules
      and other low molecular weight species in association with biomolecules can be
      determined by MRD. Such residence times are of general interest for understanding
      the kinetics of biomolecule-ligand interactions and, when exchange is gated by
      the biomolecule, can be used to characterize large-scale conformational
      fluctuations on nanosecond-millisecond time scales. By monitoring the integrity
      and specific internal hydration sites as well as the global solvent exposure, the
      MRD method can also shed light on the structure and dynamics of biomolecules in
      fluctuating nonnative states. Because it does not rely on high resolution, the
      MRD method is also applicable to very large biomolecules and complexes and has
      even been used to investigate protein crystals, gels, and biological tissues. In
      fact, dynamic studies of solids and liquid crystals were among the earliest
      applications of the MRD method. In many of its diverse applications, the MRD
      method provides unique information, complementing that available from high
      resolution NMR.

PMID- 11460549
TI  - Nuclear magnetic resonance-based approaches for lead generation in drug
      discovery.

PMID- 11460550
TI  - Screening of compound libraries for protein binding using flow-injection nuclear
      magnetic resonance spectroscopy.

PMID- 11460551
TI  - The Internet for nuclear magnetic resonance spectroscopists.

PMID- 11460552
TI  - Solid-phase synthesis of selectively labeled DNA: applications for
      multidimensional nuclear magnetic resonance spectroscopy.
AB  - The solid-phase chemical synthesis method has a strong advantage over the
      enzymatic method for preparing selectively labeled DNA oligomers. Atom-specific
      and fully labeled 2'-deoxynucleosides are economically prepared with routinely
      available isotope precursors using this synthetic route. Special DNA oligomers
      prepared by advanced labeling techniques are needed for advanced NMR
      applications, and chemical synthesis is the method of choice to respond to such
      demands. As a summary of this chapter, two tables are given. Table I lists the
      labeled nucleosides reported to be available by chemical syntheses. Table II
      lists the NMR studies using labeled DNA oligomers that were prepared by chemical
      syntheses.

PMID- 11460553
TI  - Uniform 13C/15N-labeling of DNA by tandem repeat amplification.
AB  - An optimized procedure has been described for the large-scale production of
      stable isotopeenriched duplex oligonucleotides of designed sequence. Large-scale
      production of labeled nucleotide triphosphates can be produced in this procedure
      simultaneously with labeled proteins, thereby providing synthetic dNMP precursors
      at no additional cost. The procedure is robust, with a minimum product:template
      yield of 800:1 overall, and produces > 99% single-length product. Tandem repeat
      PCR amplification is a general approach to large scale synthesis of duplex
      oligonucleotides and may have applications to both NMR and X-ray methods,
      particularly for product lengths in excess of 25 base pairs where failed
      sequences from solid-phase synthesis can be difficult to remove
      chromatographically. A drawback of the present approach is that the product is a
      duplex of two equal-length strands, making single-stranded products more
      difficult to prepare. For this reason, it could be preferable to produce single
      stranded products by the [figure: see text] method of Zimmer and Crothers.
      Although a single base type can be selectively enriched in this approach,
      chemical synthesis will provide greater flexibility for labeled DNAs requiring
      site-specific labels at only one or a small number of nucleotide positions in the
      sequence. Therefore, maximum flexibility in labeling patterns can be realized by
      judicious choice of labeling method appropriate to the type of DNA product and
      extent of isotopic enrichment desired.

PMID- 11460554
TI  - Use of chemical shifts in macromolecular structure determination.

PMID- 11460555
TI  - 13C isotopic enrichment for nuclear magnetic resonance studies of carbohydrates
      and glycoconjugates.

PMID- 11460556
TI  - Preparation and use of 2H-labeled RNA oligonucleotides in nuclear magnetic
      resonance studies.

PMID- 11460557
TI  - Investigation of unusual DNA motifs.

PMID- 11460558
TI  - Cross-correlated relaxation for measurement of angles between tensorial
      interactions.

PMID- 11460559
TI  - Resonance assignment and structure determination for RNA.

PMID- 11460560
TI  - Solution nuclear magnetic resonance probing of cation binding sites on nucleic
      acids.

PMID- 11460561
TI  - Identification and characterization of metal ion binding sites in RNA.

PMID- 11460562
TI  - Applications of adiabatic pulses in biomolecular nuclear magnetic resonance.

PMID- 11460563
TI  - Neurohormonal regulation of the insulin stimulus-secretion coupling in pancreatic
      islets.
AB  - Type 2 diabetes mellitus, a major health care problem in the Western world, is a
      disease typified by a relative deficiency of insulin, leading to vast
      derangements in glucose and lipid homeostasis with disastrous vascular
      complications. Despite immense research efforts aiming at a clear understanding
      of the etiology of this complex disease, the molecular mechanisms causing the
      disorder still remain elusive. Here we review extant data from recent
      publications implicating novel signal transduction pathways and neurohormonal
      agonists as important regulators of the insulin stimulus-secretion coupling in
      the pancreatic beta-cell. Specifically, attention is paid to incretins such as
      glucagon-like peptide 1 (GLP-1), galanin, and other peptides produced in the
      gastrointestinal tract and by neuronal cells with the potential of governing beta
      cell function in physiological and diabetic states.

PMID- 11460564
TI  - Integration of biochemical and physiologic effects of insulin on glucose
      metabolism.
AB  - The major effects of insulin on tissues are: (1) Carbohydrate metabolism: (a) It
      increases the rate of transport of glucose across the cell membrane in adipose
      tissue and muscle, (b) it increases the rate of glycolysis in muscle and adipose
      tissue, (c) it stimulates the rate of glycogen synthesis in a number of tissues,
      including adipose tissue, muscle, and liver. It also decreases the rate of
      glycogen breakdown in muscle and liver, (d) it inhibits the rate of
      glycogenolysis and gluconeogenesis in the liver. (2) Lipid metabolism: (a) It
      decreases the rate of lipolysis in adipose tissue and hence lowers the plasma
      fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in
      tissues, although only to a minor extent in humans, (c) it increases the rate of
      very-low-density lipoprotein formation in the liver, (d) it increases the uptake
      of triglyceride from the blood into adipose tissue and muscle, (e) it decreases
      the rate of fatty acid oxidation in muscle and liver, (f) it increases the rate
      of cholesterol synthesis in liver. (3) Protein metabolism: (a) It increases the
      rate of transport of some amino acids into tissues, (b) it increases the rate of
      protein synthesis in muscle, adipose tissue, liver, and other tissues, (c) it
      decreases the rate of protein degradation in muscle (and perhaps other tissues),
      (d) it decreases the rate of urea formation.--These insulin effects serve to
      encourage the synthesis of carbohydrate, fat and protein.

PMID- 11460565
TI  - Insulin resistance: definition and consequences.
AB  - Insulin resistance is defined clinically as the inability of a known quantity of
      exogenous or endogenous insulin to increase glucose uptake and utilization in an
      individual as much as it does in a normal population. Insulin action is the
      consequence of insulin binding to its plasma membrane receptor and is transmitted
      through the cell by a series of protein-protein interactions. Two major cascades
      of protein-protein interactions mediate intracellular insulin action: one pathway
      is involved in regulating intermediary metabolism and the other plays a role in
      controlling growth processes and mitoses. The regulation of these two distinct
      pathways can be dissociated. Indeed, some data suggest that the pathway
      regulating intermediary metabolism is diminished in type 2 diabetes while that
      regulating growth processes and mitoses is normal.--Several mechanisms have been
      proposed as possible causes underlying the development of insulin resistance and
      the insulin resistance syndrome. These include: (1) genetic abnormalities of one
      or more proteins of the insulin action cascade (2) fetal malnutrition (3)
      increases in visceral adiposity. Insulin resistance occurs as part of a cluster
      of cardiovascular-metabolic abnormalities commonly referred to as "The Insulin
      Resistance Syndrome" or "The Metabolic Syndrome". This cluster of abnormalities
      may lead to the development of type 2 diabetes, accelerated atherosclerosis,
      hypertension or polycystic ovarian syndrome depending on the genetic background
      of the individual developing the insulin resistance.--In this context, we need to
      consider whether insulin resistance should be defined as a disease entity which
      needs to be diagnosed and treated with specific drugs to improve insulin action.

PMID- 11460566
TI  - Pathogenesis of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is a heterogeneous disorder with genetic and acquired
      components. It is primarily due to impaired insulin secretion in that individuals
      with genetically impaired beta cell function cannot increase their insulin
      release sufficiently to compensate for insulin resistance. The resultant
      hyperglycemia is largely the consequence of excessive release of endogenous
      glucose due to increased gluconeogenesis. Nevertheless, clinical experience has
      demonstrated that therapies directed at improving beta cell function
      (sulfonylureas) and at improving hepatic (metformin) and muscle
      (thiazolidinediones) insulin sensitivity are effective treatments for the
      condition.

PMID- 11460567
TI  - Glucose effectiveness: measurement in diabetic and nondiabetic humans.
AB  - It is well established that under the conditions of daily living, insulin
      secretion and insulin action determine glucose tolerance in nondiabetic humans
      both in the post-absorptive and post-prandial states. However, in recent years,
      glucose effectiveness (i.e., the ability of glucose per se to stimulate its own
      uptake and to suppress its own release) has also been shown to influence glucose
      tolerance in both diabetic and nondiabetic individuals. In states of deficient
      insulin action, e.g., in individuals with type 2 diabetes, glucose effectiveness
      assumes a greater role in determining glucose tolerance both during fasting and
      post-prandial conditions. A mathematical model (Minimal Model) of glucose
      turnover has been applied to estimate glucose effectiveness in both diabetic and
      nondiabetic individuals. Several investigators have demonstrated reduced glucose
      effectiveness in people with type 2 diabetes mellitus. However, measurements of
      glucose effectiveness by the traditional single compartment minimal model
      approach have been fraught with errors when compared to model independent
      estimates, especially in the diabetic population. This has led investigators to
      modify the parameters of the model with the incorporation of glucose tracers and
      the use of two-compartment model of glucose kinetics. Although this has made the
      indices of glucose effectiveness more robust, proper validation experiments are
      necessary before widespread application of these methods.

PMID- 11460568
TI  - The endothelium as a metabolic and endocrine organ: its relation with insulin
      resistance.
AB  - The vascular endothelium, building the inner layer of capillaries and blood
      vessels of all sorts, represents a highly active metabolic and endocrine organ
      producing a multitude of different molecules, including vasoactive peptide
      hormones, growth factors, coagulation factors and adhesion molecules. In
      addition, it expresses many of the respective endocrine, paracrine and
      cytokine/growth factor receptors. It thereby regulates the delicate balance
      between vasoconstriction and vasodilation, between coagulation and fibrinolysis,
      proliferation and apoptosis, as well as between transient adhesion and diapedesis
      of blood borne leukocytes. This minireview addresses the potential interactions
      of these important functions in the states of diabetes and of insulin resistance
      including obesity, hypertension and dyslipidaemia, all of which characterized by
      endothelial dysfunction.

PMID- 11460569
TI  - Pathogenesis of dyslipidemia in type 2 diabetes.
AB  - The recognition that hypertriglyceridemia is associated with multiple alterations
      of other lipoproteins that are potentially atherogenic has expanded the picture
      of diabetic dyslipidemia. Elevation of large VLDL1 particles initiate a sequence
      of events that results in generation of atherogenic lipoproteins including
      remnants and small dense LDL. This abnormality is also associated with the
      lowering of HDL cholesterol. The clinical implication is that the concentration
      of plasma triglycerides should be maintained as low as possible to avoid these
      deleterious consequences of hypertriglyceridemia.

PMID- 11460570
TI  - The role of lipids in the pathogenesis of muscle insulin resistance and beta cell
      failure in type II diabetes and obesity.
AB  - This review considers evidence for, and putative mechanisms of, lipid-induced
      muscle insulin resistance. Acute free fatty acid elevation causes muscle insulin
      resistance in a few hours, with similar muscle lipid accumulation as accompanies
      more prolonged high fat diet-induced insulin resistance in rodents. Although
      causal relations are not as clearcut in chronic human insulin resistant states
      such as obesity and type 2 diabetes, it is now recognised that muscle lipids also
      accumulate in these states. The classic Randle glucose-fatty acid cycle is only
      one of a number of mechanisms by which fatty acids might influence muscle glucose
      metabolism and insulin action. A key factor is seen to be accumulation of muscle
      long chain acyl CoAs, which could alter insulin action via several mechanisms
      including chronic activation of protein kinase C isoforms or ceramide
      accumulation. These interactions are fundamental to understanding metabolic
      effects of new insulin "sensitizers", e.g. thiazolidinediones, which alter lipid
      metabolism and improve muscle insulin sensitivity in insulin resistant states.
      Recent work has also pointed to a possible role of lipids in beta cell
      deterioration ("lipotoxicity") associated with type 2 diabetes.

PMID- 11460571
TI  - Nutritional regulation of lipid metabolism in human adipose tissue.
AB  - Pfeiffer and colleagues years ago pointed out that different distributions and
      amounts of adipose tissue are associated with abnormalities of lipolysis and
      lipoprotein metabolism. Adipose tissue has several crucial roles including (i)
      mobilization from stores of fatty acids as an energy source, (ii) catabolism of
      lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release
      of hormonal signals such as leptin and interleukin-6. These adipose tissue
      actions are crucially regulated by nutrition. The review considers the existence
      of metabolic pathways and modes of regulation within adipose tissue, and how such
      metabolic activity can be quantitated in humans. Nutrition can influence adipose
      tissue at several 'levels'. Firstly the level of obesity or malnutrition has
      important effects on many aspects of adipose tissue metabolism. Secondly short
      term overfeeding, underfeeding and exercise have major impacts on adipose tissue
      behaviour. Lastly, specific nutrients are capable of regulating adipose tissue
      metabolism. Recently there have been considerable advances in understanding
      adipose tissue metabolism and in particular its regulation. This review discusses
      the behaviour of adipose tissue under various nutritional conditions. There is
      then a review of recent work examining the ways in which nutritional influences
      act via intra-cellular mechanisms, insulin and the sympathetic innervation of
      adipose tissue.

PMID- 11460572
TI  - Obesity: causes and new treatments.
AB  - The prevalence of obesity increases rapidly in developed and developing
      countries. Obesity results from a cumulative positive energy balance and is
      favoured by both genetic and environmental factors. Preventing obesity requires a
      major investment in nutritional and lifestyle education, particularly in children
      and adolescents.--The pharmacological approach to obesity includes drugs that
      reduce food intake (noradrenergic and serotoninergic agents), drugs that increase
      energy expenditure and compounds that affect nutrient partitioning. In all
      instances, the benefit-to-risk ratio needs to be carefully assessed. In some
      patients (severe obesity or obesity accompanied by serious high-risk comorbid
      conditions), gastric surgery (gastric restriction or gastric bypass) should be
      considered. In our own experience, it is safe and effective.

PMID- 11460573
TI  - Thyroid hormone excess and glucose intolerance.
AB  - The elevated plasma glucose levels in hyperthyroidism may be explained by
      increased rates of endogenous glucose production, due mainly to increased
      gluconeogenesis. The rates of insulin-stimulated glucose disposal in peripheral
      tissues in hyperthyroidism have been found, in general, either normal or
      increased. Skeletal muscle is the most important tissue for the disposal of
      glucose in response to insulin. In this tissue, insulin increases glucose
      disposal by stimulating glucose transport, glucose phosphorylation/glycolysis,
      glycogen synthesis and glucose oxidation. Studies examining insulin-stimulated
      glucose metabolism in skeletal muscle have suggested that, in the hyperthyroid
      state, it may be of primary importance to increase the rates of glycolysis and
      lactate formation relative to glucose oxidation in this tissue in order to
      provide substrate for gluconeogenesis (increase Cori cycle activity). This effect
      will be achieved primarily by a decrease in glycogen synthesis and an increase in
      glycogenolysis. When hyperthyroidism becomes more severe, an increased rate of
      glucose uptake into muscle may then be necessary since the increased conversion
      of glycogen to lactate could not be sustained for prolonged periods and might
      lead to a depletion in glycogen stores. This mechanism would ensure that the
      level of glucose in plasma is kept normal or slightly increased. Thus, an
      increased Cori cycle activity may be a necessary mechanism to provide optimal
      conditions in hyperthyroidism for the control of glucose utilization without
      increasing the risk of hypoglycemia. In addition to lactate, increased rates of
      gluconeogenesis in hyperthyroidism can also be sustained by increased plasma
      concentrations of amino acids (mostly glutamine and alanine) and glycerol, as
      well as by increased plasma concentrations of free fatty acids.

PMID- 11460574
TI  - Strategies for the prevention of type 2 diabetes.
AB  - Type 2 diabetes is a common chronic disease affecting more than 100 millions of
      people world-wide, and is a major cause of premature morbidity and mortality.
      Macrovascular disease and its risk factors are often already present in
      individuals at risk for type 2 diabetes, and some of the risk factors for the
      development of type 2 diabetes, such as obesity, physical inactivity, and high
      fat diet, can potentially be modified. Because some of the metabolic
      abnormalities, such as insulin resistance or impaired glucose tolerance, that
      indicate a risk for diabetes can be improved by lifestyle modification and drug
      treatment, strategies for the prevention of type 2 diabetes appear to be
      necessary for affected individuals. Several clinical trials have addressed the
      hypothesis that type 2 diabetes can be prevented by dietary modification,
      physical activity, or drug treatment. Although some of these studies indicate a
      protective effect of these measures against the development of type 2 diabetes in
      people at risk, many of their conclusions are limited with respect to
      randomisation, sample size, or intensity of the intervention. In the large
      prospective Da Qing study (1997), both dietary and physical activity
      interventions reduced the incidence of type 2 diabetes considerably in a Chinese
      population. Whether this is also achievable in other ethnic populations at high
      risk for developing type 2 diabetes, and whether additional pharmacological
      measures are useful, is currently under investigation.

PMID- 11460575
TI  - Nutrition in diabetes mellitus.
AB  - Diet is very important in the treatment of diabetes mellitus. An energy deficit
      of about 500 Kcal per day is recommended for most overweight diabetic patients in
      order to progressively achieve a weight loss.--According to the most recent
      recommendations of the Nutrition Study Group of the European Association for the
      Study of Diabetes, 60 to 70% of the total daily energy should be covered from a
      combination of carbohydrates and monounsaturated fatty acids with a cis
      configuration. The percentage of energy contributed by each may vary according to
      individual preferences and clinical characteristics. It is, also, important to
      reduce the intake of saturated and trans unsaturated fatty acids (< 10% total
      energy). Protein intake should not exceed 20% total energy intake. Rich in fibre
      and/or antioxidant carbohydrate containing foods (fruits, vegetables, legumes) or
      those with a low glycaemic index are strongly recommended. Moderate amounts of
      foods rich in omega 3-fatty acids (mainly oily fish) should be regularly
      consumed.

PMID- 11460576
TI  - Metformin, the rebirth of a biguanide: mechanism of action and place in the
      prevention and treatment of insulin resistance.
AB  - Metformin should be regarded as a first-choice therapy of type 2 diabetes,
      showing an especially good efficacy in obese patients with hyperinsulinaemia.
      Reduction of blood glucose without hyperinsulinaemia and without hypoglycaemia,
      favourable influence on the lipid profile and inhibition of coagulation factors
      lead to an antidiabetic and antiatherogenic effect. Not only are these
      characteristics relevant to judging the value of the drug, but also the strict
      observation of contraindications is needed to avoid the dangerous complication of
      lactic acidosis.

PMID- 11460577
TI  - Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and
      insulin sensitizers.
AB  - In this review we present the agents that are in use in the treatment of type 2
      diabetes. Sulfonylureas of the 1st and 2nd generation increase insulin secretion
      but can induce hyperinsulinemia and sometimes prolonged hypoglycemia. Glimepiride
      is a new 3rd generation sulfonylurea with some advantages over the other members
      of this group, such as a lower risk of hypoglycemia, no interaction with
      cardiovascular KATP-channels and a possibility that it may increase insulin
      sensitivity. There are also newer insulin secretagogues (such as neteglinide and
      repaglinide) with a rapid onset of action on the beta-cell, therefore inducing a
      more physiological profile of insulin secretion during meals. The category of
      insulin sensitizers includes metformin and thiazolidinediones. Metformin
      effectively reduces hyperglycemia, hyperlipidemia and macroangiopathy in patients
      with type 2 diabetes. This agent increases the sensitivity of the liver and
      peripheral tissues to insulin and, therefore, it could be considered as a drug of
      choice for the prevention of type 2 diabetes. Thiazolidinediones (rosiglitazone
      and pioglitazone) increase the sensitivity of the tissues to insulin. This
      mechanism of action makes them powerful therapeutic tools for the treatment of
      type 2 diabetes (and possibly other insulin resistant states) either alone or in
      combination with other oral agents. The category of agents that interfere with
      the absorption of glucose and lipids includes alpha-glucosidase inhibitors
      (acarbose and miglitol) and lipase inhibitors (or-listat). alpha-Glucocidase
      inhibitors improve the time relationship between plasma insulin and glucose
      increases after a meal. Therefore, these agents may be used in the treatment of
      patients with type 2 diabetes, either alone at a very early stage of this disease
      (when insulin secretion is still adequate), or in combination with insulin
      secretagogues. alpha-Glucosidase inhibition may also prove useful as a supplement
      to insulin therapy in patients with type 1 diabetes mellitus. The inhibitor of
      gastrointestinal lipase orlistat may prove a useful adjunct to hypocaloric diets
      in patients with type 2 diabetes and obesity.

PMID- 11460578
TI  - The entero-insular axis in type 2 diabetes--incretins as therapeutic agents.
AB  - The search for intestinal factors regulating the endocrine secretion of the
      pancreas started soon after the discovery of secretin, i.e. nearly 100 years ago.
      Insulinotropic factors of the gut released by nutrients and stimulating insulin
      secretion in physiological concentrations in the presence of elevated blood
      glucose levels have been named incretins. Of the known gut hormones only gastric
      inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1 [7-36] amide)
      fulfill this definition.--The incretin effect (i.e. the ratio between the
      integrated insulin response to an oral glucose load and an isoglycaemic
      intravenous glucose infusion) is markedly diminished in patients with type 2
      diabetes mellitus, while the plasma levels of GIP and GLP-1 and their responses
      to nutrients are in the normal range. Therefore, a reduced responsiveness of the
      islet B-cells to incretins has been postulated. This insensitivity of the
      diabetic B-cells towards incretins can be overcome by supraphysiological
      (pharmacological) concentrations of GLP-1 [7-36], however not of GIP.
      Accordingly, fasting and postprandial glucose levels can be normalized in
      patients with type 2 diabetes by infusions of GLP-1 [7-36]. Further studies
      revealed that this is partially due to the fact that GLP-1 [7-36]--in addition to
      its insulinotropic effect--also inhibits glucagon secretion and delays gastric
      emptying. These three antidiabetic effects qualify GLP-1 [7-36] as an interesting
      therapeutic tool, mainly for type 2 diabetes. However, because of its short
      plasma half life time natural GLP-1 [7-36] is not suitable for subcutaneous
      application. At present methods are being developed to improve the
      pharmacokinetics of GLP-1 by inhibition of the cleaving enzyme dipeptidyl
      peptidase IV (DPP-IV) or by synthesis of DPP-IV resistant GLP-1 analogues. Also
      naturally occurring GLP-1 analogues (for instance exendin-4) with a much longer
      half life time than GLP-1 [7-36] are being tested.--Thus, after 100 years of
      speculations and experimentations, incretins and their analogues are emerging as
      new antidiabetic drugs.

PMID- 11460579
TI  - Modern concepts for the prediction of type 1 diabetes.
AB  - Type 1 diabetes results from the destruction of the insulin-producing beta cells
      of the pancreas. The disease process is thought to be initiated by a complex
      interaction between genetic and environmental factors leading to a cellular and
      humoral autoimmune response against beta cell specific components. Over the past
      decade there has been important progress in identification of several diabetes
      specific autoantigens. The availability of recombinant antigens, most notably the
      enzyme glutamic acid decarboxylase (GAD) and the tyrosine phosphatase-like
      molecule IA-2, made it possible to develop simple, sensitive and specific
      radioimmunoassays for the detection of autoantibodies on a large scale. It has
      been shown that the combination of GAD antibodies (GADA) and IA-2 antibodies (IA
      2-A) with insulin autoantibodies (IAA) can replace the conventional ICA test.
      This considerably facilitates screening programmes. Prospective studies in
      subjects with and without family history of type 1 diabetes conclusively
      demonstrate that the risk for type 1 diabetes is strongly correlated with the
      number of positive antibodies. The 5-10-years risk for type 1 diabetes varies
      from 0-1% in individuals with only one positive antibodies to 62-100% in subjects
      who were positive for three or more antibodies. Despite the identification of
      novel genetic markers associated with type 1 diabetes, the major
      histocompatibility complex, namely HLA-DQ alleles, still represents the strongest
      genetic risk factor. The analysis of HLA-DQ alleles may be important to
      discriminate between subjects at high or intermediate risk from antibody positive
      individuals carrying protective haplotypes. Assessment of the metabolic state
      using the first phase insulin response to intravenous glucose may provide
      additional information to predict rapid progression to diabetes. Screening for
      multiple antibodies is the most specific and sensitive strategy for identifying
      subject at risk for type 1 diabetes. Second-line genotyping or analysis of the
      first phase insulin response can serve as useful tool to improve the prediction
      of type 1 diabetes. The value of additional markers such as isotype specific
      autoantibodies or T-helper cells subsets measured by ELISPOT assays or FACS
      remains to be shown.

PMID- 11460580
TI  - Physiological insulin replacement in type 1 diabetes mellitus.
AB  - The DCCT and UKPDS studies have definitely established that in type 1 as well as
      in type 2 diabetes mellitus, long-term near-normoglycaemia strongly protects
      against onset and/or progression of microangiopathic complications. Therefore,
      implementation of insulin strategies to maintain long-term near-normoglycaemia is
      of key importance in the management of diabetes mellitus. To successfully reach
      the goal of near-normoglycaemia, insulin therapy has to be physiological, i.e. it
      has to mimic nature by providing a bolus of insulin at meal ingestion, and by
      replacing the need for basal insulin between meals and during the night. The meal
      time insulin needs can be best met by s.c. injection of a short-acting insulin
      analogue (lispro, aspart). Short-acting insulin analogues should be preferred to
      human regular insulin for three main reasons. First, convenience (meal-time
      injection, better adaptation of insulin dose to carbohydrate content of the
      meal); second, lower blood glucose 2-hour after meals; third, less risk for late
      post-prandial hypoglycaemia. However, the benefits of meal-time treatment with
      short-acting insulin analogues become apparent only by the extent to which
      replacement of basal insulin is optimised as well. The interprandial (especially
      nocturnal) need for basal insulin can be best met by the continuous s.c. insulin
      infusion by an external minipump, the gold standard of basal insulin replacement.
      Continuous s.c. insulin infusion in the basal state is so good because it uses a
      short-acting insulin analogue (low variability in s.c. absorption, flat and peak
      less action profile), not insulin preparations with retarded action (high
      variability of s.c. absorption, peak of action) likewise the model of multiple
      daily insulin injections. A second choice option is s.c. injection of an insulin
      preparation with retarded action. At present, the long-acting insulin analogue
      glargine is the retarded insulin preparation of choice because its action profile
      is flat, peakless and long-lasting (approximately 24 hours). This is in contrast
      with the peak action profile of NPH insulin which exhibits a short duration of
      action (10-15 h). Thus, the modern insulin strategies for intensive therapy
      always include use of a short-acting insulin analogue at meal-time, and use of
      either continuous s.c. insulin infusion, or a s.c. injection of insulin glargine
      to replace basal insulin. Insulin glargine reproduces closely the
      pharmacokinetics and pharmacodynamics of continuous s.c. insulin infusion, and
      should always be preferred to NPH in all insulin-requiring diabetic patients,
      both type 1 and type 2.

PMID- 11460581
TI  - External and implantable insulin pumps: current place in the treatment of
      diabetes.
AB  - External insulin infusion (CSII) pumps have regained interest since DCCT, the
      number of patients approaching 100,000 in the USA. Only 2 manufacturers (Minimed,
      Disetronic) and 2 insulins (lispro, insuman) are sharing the market. The major
      advantages over multiple s.c. injections (MDI) are a reduction of nightly
      instability and hypoglycemia, and time flexibility. Patients poorly controlled
      under MDI and/or with recurrent hypoglycemias thus represent the best
      indications. Pumps are predicted to expand in some european countries e.g. France
      with changes in reimbursement regulations. Implantable insulin pumps are still
      not commercialized except in few countries e.g. France. Therefore only 1065 pumps
      have been implanted worldwide so far. The only material available is the Minimed
      2007 pump, with the Aventis Genapol insulin. The catheter is intraperitoneal for
      portal insulin absorption. Metabolic results are better than CSII in terms of
      glycemic fluctuations and hypoglycemias. Adverse events are limited to catheter
      obstructions (15% per patient-year). Ideally, indications should be restricted
      only to patients with recurrent severe hypoglycemias and/or poor control with
      CSII because of high cost of the pump ($ 15,000).

PMID- 11460582
TI  - Implantable glucose sensors: present status and future developments.
AB  - Implantable glucose sensors are the basis for the development of implantable
      closed loop systems for glucose control in diabetic patients. Despite the efforts
      of several research groups in the last thirty years, implantable glucose sensors
      for long-term use in diabetic patients are not available at this time. Until now,
      these research efforts resulted in the development of systems for short-term
      glucose measurement in the skin. Two systems measure glucose in the subcutaneous
      tissue by means of electroenzymatic needle electrodes or by microdialysis coupled
      to external sensor systems, one system measures glucose on the surface of the
      skin in interstitial fluid sampled by transdermal iontophoresis. At this time
      none of these systems allows glucose monitoring in daily clinical practice with
      sufficient accuracy. Moreover, most systems only allow retrospective data
      analysis. In case that present technical shortcomings of short-term sensors can
      be solved, they might be useful for improvement of diabetes therapy in selected
      clinical situations.

PMID- 11460583
TI  - Recent advances in continuous glucose monitoring.
AB  - Continuous glucose monitoring, providing more detailed information on glucose
      excursions than single spot measurements, should help to improve the therapy in
      diabetic patients and is also required for feedback-controlled insulin delivery.
      At the Institute for Diabetes-Technology in Ulm, founded by EF Pfeiffer, a
      portable glucose sensor for continuous tissue glucose monitoring has been
      developed. The combination of microdialysis and enzymatic amperometric glucose
      measurement implemented in this device marked a break-through in achieving
      reliable and precise continuous tissue glucose monitoring. In several studies, we
      have demonstrated that continuous subcutaneous glucose monitoring for up to 72
      hours is feasible under 'in-house' and 'daily life' conditions in diabetic
      patients. The measured tissue glucose concentrations correlated closely to
      glucose control measurements in venous and capillary blood. A reliable continuous
      glucose monitoring device is a prerequisite for the development of an artificial
      pancreas. Our group developed an algorithm for subcutaneous application of the
      fast acting insulin analogon lispro. In experiments performed over 7 and 24 hours
      good metabolic control was achieved by algorithm-based insulin application. In
      addition, the algorithm was able to maintain acceptable metabolic control during
      and after moderate physical exercise. Further work is needed to optimize
      continuous tissue glucose monitoring systems and to develop a closed loop system
      for insulin application based on continuously measured tissue glucose
      concentrations.

PMID- 11460584
TI  - Information systems in diabetes: in search of the holy grail in the era of
      evidence-based diabetes care.
AB  - The role of information systems has become increasingly important in the context
      of evidence-based medicine as a new decision-making paradigm, in the evolution of
      new forms of medical records and communication structures, and in the redesign of
      traditional systems of care towards planned care of chronic disease. In this
      review we describe the past and current forms of communication and clinical
      information transfer dedicated to improving the delivery of diabetes care. In
      particular, we describe our experience with the implementation of an electronic
      diabetes medical record system and specialist overview using telemedicine.

PMID- 11460585
TI  - Islet transplantation as treatment of type 1 diabetes: from experimental
      beginnings to clinical application.
AB  - Experimental islet transplantation started more than 30 years ago when it was
      discovered that isolation of the islets of Langerhans from the exocrine tissue of
      the pancreas was possible with collagenase. In numerous studies over the
      following years in rodents it was shown that transplantation of a sufficient
      number of islets into the liver via the portal vein shortly after diabetes
      induction of the recipient resulted in normoglycemia, aglycosuria, normal body
      weight and the typical diabetic late complications were prevented. However, those
      results were limited for the syngeneic system, when allogeneic islets were
      transplanted rejection occurred within a few days. Immunosuppressive regimen
      showed only limited success in rodents while immunoalteration procedures (culture
      at low temperatures, UV light irradiation, cryopreservation etc.) were capable to
      prolong the survival of islets up to 200 days. In contrast to the rodent model in
      larger animals as pigs, dogs and monkeys immunosuppressive drugs (single and in
      combination) resulted in marked prolongation of allograft survival while
      immunoalteration of islets with those animals was less successful. Because a
      broader use of islet transplantation in man will lead to shortage of donor organs
      xenotransplantation may be possibly a solution which is briefly mentioned.-
      Finally, new strategies regarding the production of human insulin producing cells
      for transplantation purposes are discussed.--In summary, experimental islet
      transplantation has paved the way for using this treatment in human patients.

PMID- 11460586
TI  - Islet transplantation: present clinical situation and future aspects.
AB  - Beta-cell replacement either by pancreatic organ or islet cell transplantation is
      the only treatment to achieve an insulin-independent, normoglycemic state and to
      avoid hypoglycemic episodes in patients with type 1 diabetes mellitus. This
      article will review the state-of-the-art in clinical islet cell transplantation
      at the dawn of the new millennium and will provide an outlook on the basis of
      extended personal experience.

PMID- 11460587
TI  - Gestational diabetes: current aspects on pathogenesis and treatment.
AB  - Gestational diabetes (GDM) is a carbohydrate intolerance resulting in
      hyperglycaemia of variable severity with onset or first recognition during
      pregnancy. The incidence of GDM is between 0.15-15%, which corresponds to the
      prevalence of type 2 diabetes and IGT in a given country.--The predominant
      pathogenic factor in GDM could be the inadequate insulin secretion. If GDM is not
      properly treated the risk of adverse maternal (preeclampsia) and fetal (large-for
      gestational-age infant, macrosomia, birth trauma, cesarean section, still-birth)
      outcome increases. Hypertension is more prevalent in GDM, and GDM is diagnosed
      more frequently in women with chronic hypertension.--In order to screen for
      disturbances of carbohydrate metabolism during pregnancy a simple method suitable
      for all pregnant women would be desirable, however no such method is available at
      present. According to the latest WHO recommendation the screening for GDM should
      be performed universally with the standard 75 g oGTT evaluating only the 2-hour
      blood glucose values or together with the fasting ones. The latter could provide
      even an exact diagnosis of the carbohydrate metabolic state.--To manage GDM the
      first step prompt after diagnosis is to educate adequate dietary needs. If the
      blood sugar values in spite of an adequate diet exceed the desirable target
      values, insulin treatment has to be initiated.--GDM is a predictor of diabetes
      (mainly type 2) later in life. The cumulative incidence of type 2 diabetes is
      about 50% at 5 years. This review of the current literature including our own
      experience strongly supposes that prior GDM is also a predictor or even an early
      manifestation of the metabolic (insulin resistance) syndrome. By all means GDM is
      a cardiovascular risk factor that could be screened to prevent late
      complications. The previously presented evidence also strongly suggests that
      yearly check-ups for women with previous GDM are inevitably important.

PMID- 11460588
TI  - Hypoglycemia risk reduction in type 1 diabetes.
AB  - Hypoglycemia is the limiting factor in the glycemic management of diabetes
      because it generally precludes maintenance of euglycemia. Improving glycemic
      control while minimizing hypoglycemia in type 1 diabetes mellitus (T1 DM)
      involves both application of the principles of aggressive therapy--patient
      education and empowerment, frequent self monitoring of blood glucose, flexible
      insulin regimens, individualized glycemic goals and ongoing professional guidance
      and support--and implementation of hypoglycemia risk reduction. Iatrogenic
      hypoglycemia is the result of the interplay of therapeutic insulin excess and
      compromised physiological and behavioral defenses against falling plasma glucose
      concentrations in T1 DM. Relative or absolute insulin excess occurs when insulin
      doses are excessive, ill-timed or of the wrong type, when exogenous glucose
      delivery, endogenous glucose production or insulin clearance are decreased or
      when insulin-independent glucose utilization or sensitivity to insulin are
      increased. But these conventional risk factors explain only a minority of
      episodes of severe hypoglycemia. More potent risk factors include absolute
      insulin deficiency, a history of severe hypoglycemia and aggressive therapy per
      se as evidenced by lower glycemic goals, lower hemoglobin A1c levels, or both.
      These are clinical surrogates of compromised glucose counterregulation, the
      clinical syndromes of defective glucose counterregulation (the result of absent
      decrements in insulin and absent increments in glucagon with attenuated
      increments in epinephrine) and hypoglycemia unawareness (the result of reduced
      autonomic [sympathochromaffin] activation causing reduced warning symptoms of
      developing hypoglycemia). The unifying concept of hypoglycemia-associated
      autonomic failure in T1 DM posits that: (1) Periods of relative or absolute
      therapeutic insulin excess in the setting of absent glucagon responses lead to
      episodes of hypoglycemia. (2) These episodes, in turn, cause reduced autonomic
      (including adrenomedullary) responses to falling glucose concentrations on
      subsequent occasions. (3) These reduced autonomic responses result in both
      reduced symptoms of developing hypoglycemia (i.e., hypoglycemia unawareness) and-
      because epinephrine responses are reduced in the setting of absent glucagon
      responses--impaired physiological defenses against developing hypoglycemia (i.e.,
      defective glucose counterregulation). Thus a vicious cycle of recurrent
      hypoglycemia is created and perpetuated. Hypoglycemia risk reduction includes,
      first, addressing the issue of hypoglycemia--the patient's awareness of and
      concerns about it, its frequency, severity, timing and clinical settings--in
      every patient contact. Then it requires application of the principles of
      aggressive therapy, consideration of both the conventional risk factors and those
      indicative of compromised glucose counterregulation and appropriate regimen
      adjustments including a two to three week period of scrupulous avoidance of
      hypoglycemia in patients with hypoglycemia-associated autonomic failure. With
      this approach the goals of improving glycemic control and minimizing hypoglycemia
      are not incompatible.

PMID- 11460589
TI  - Pathogenesis of diabetic nephropathy.
AB  - Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure
      (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical
      course, starting with microalbuminuria through proteinuria, azotaemia and
      culminating in ESRF. Before the onset of overt proteinuria, there are various
      renal functional changes including renal hyperfiltration, hyperperfusion, and
      increasing capillary permeability to macromolecules. Basement-membrane thickening
      and mesangial expansion have long been recognized as pathological hallmark of
      diabetes. It has been postulated that DN occurs as a result of the interplay of
      metabolic and hemodynamic factors in the renal microcirculation. There is no
      doubt that there is a positive relationship between hyperglycaemia, which is
      necessary but not sufficient, and microvascular complications. The accumulation
      of advanced glycosylated end-products (AGEs), the activation of isoform(s) of
      protein kinase C (PKC) and the acceleration of the aldose reductase pathway may
      explain how hyperglycemia damages tissue. PKC is one of the key signaling
      molecules in the induction of the vascular pathology of diabetes. The balance
      between extracellular matrix production and degradation is important in this
      context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal
      role in accumulation in the diabetic kidney. Hemodynamic disturbances are
      believed to be directly responsible for the development of glomerulosclerosis and
      its attendant proteinuria. There is familial clustering of diabetic kidney
      disease. A number of gene loci have been investigated to try to explain the
      genetic susceptibility to diabetic nephropathy. The genes coding for components
      of renin-angiotensin system have drawn special attention, due to the central role
      that this system plays in the regulation of blood pressure, sodium metabolism,
      and renal hemodynamics. Endothelial dysfunction is closely associated with the
      development of diabetic retinopathy, nephropathy and atherosclerosis, both in
      IDDM and in NIDDM. The pathogenesis of diabetic nephropathy is not clarified
      completely yet.

PMID- 11460590
TI  - New concepts in pathogenesis and treatment of diabetic retinopathy.
AB  - Retinal neovascularization is a major feature of proliferative diabetic
      retinopathy, which represents a major public health problem, being responsible
      for more irreversible blindness in persons of middle and older age than any other
      pathology. The societal burden of ocular neovascularization has prompted
      extensive research into its mechanisms. The aim of this review will be to briefly
      summarize the current knowledge regarding the clinical and laboratory findings of
      diabetic retinopathy. From an investigational view, studies of ocular
      neovascularization provide important informations, often permitting real-time,
      serial observations of neovascularization in vivo. This allows investigators to
      analyse the relevance of specific pathogenic concepts regarding the mechanisms of
      angiogenesis in vivo. This review will additionally describe current concepts
      regarding the pathogenesis and treatment of diabetic retinopathy.

PMID- 11460591
TI  - Small fiber neuropathy and neurovascular disturbances in diabetes mellitus.
AB  - Functional and organic abnormalities in small unmyelinated C fibers are the
      hallmark of type 2 diabetes. These may be silent clinically or present with
      burning feet, neurovascular abnormalities, wherein warm, cold, and heat pain
      thresholds are disturbed in association with impairment in skin blood flow and
      loss of PGP 9.5 immunostaining nerves in the skin. There is a dysfunctional phase
      preceding organic structural damage to the neurovascular unit. It coexists with
      elements of the metabolic syndrome, particularly insulin resistance (IR),
      elevated systolic blood pressure, and diabetic dyslipidemia i.e. dysfunction of
      the neurovascular unit may contribute to IR due to compromised blood flow with
      decreased delivery of fuels to their target tissues. If this proves to be the
      case, it will become important to re-focus energies on the defective
      neuropeptidergic regulation of blood flow as an approach to ameliorating
      diabetes. Because there is a functional phase that precedes structural damage,
      reversibility of the defect is achievable.

PMID- 11460592
TI  - Macrovascular disease in diabetes: current status.
AB  - Clearly, macrovascular complications are the prognosis limiting problem of
      diabetes patients which consecutively account for the majority of socio-economic
      burden of the disease. The overall morbidity and mortality development does not
      indicate improvement hallmarking better or at least adequate care for these
      patients. Possible explanations address the late detection problem of a
      clinically silent disease onset as well as unrecognised multiple comorbid
      conditions all of which end-up with endothelial dysfunction as representation of
      the so called "functional atherosclerosis" and blood hyperresponsiveness. Here,
      we describe new experimental aspects of the early atherosclerosis development
      focussing inflammation as one driving pathogenetic force for the evolution of the
      complicated lesion type in diabetes. However, emphasis is put on the view that
      inflammation, atherogenesis and thrombogenesis are severely crosslinked by
      soluble and cellular adhesion molecules. From a diagnostic point of view genomic
      detection of risk associated genes opens both the vision of early identification
      of high risk individuals and the targeting of drug intervention based on
      conditioned responsiveness. By using available drugs and evidence based risk
      factor intervention strategies a plea is made for a multimodal therapeutic
      approach fitted to the individual patient's needs aiming at endpoint reduction.
      This corresponds to the recent releases of guidelines from nearly all vascular
      medicine related scientific societies. Diabetes is a vascular disease!

PMID- 11460593
TI  - The atherosclerotic process and its exacerbation by diabetes.
AB  - The excess of glucose appears to play an important and specific role in the
      genesis of macroangiopathy in diabetics. Activation of protein kinase-C, the
      sorbitol pathway, and AGE formation are thought to be the major pathways linking
      the degree of glycaemic compensation with the pathogenetic process of
      macrovascular disease. HSPG is likely to be a key element in this process since
      it is a regulator of endothelial permeability, vascular antithrombotic capacity,
      insulin sensitivity (with respect to lipoprotein lipase availability), and
      vascular extracellular matrix content and smooth-muscle-cell activation. Loss of
      HSPG is suggested clinically by the presence of microalbuminuria, to the
      development of which diabetic control also contributes significantly. However,
      genetic factors also seem to be involved. Much more insight into the precise
      mechanismus is necessary to unravel the cellular and molecular chains of events
      for the premature and accelerated atherosclerosis in diabetic patients.

PMID- 11460595
TI  - Ernst F. Pfeiffer: his impact on diabetes research and treatment over the last 45
      years.

PMID- 11460594
TI  - Diabetes mellitus a risk for osteoporosis?
AB  - Localized lesions at the foot skeleton are a serious and well recognized
      complication of diabetes mellitus which may impair the clinical outcome of the
      patients remarkably. In contrast, the presence of a generalized bone disease or
      osteoporosis related to diabetes mellitus is less acknowledged and its clinical
      relevance is less obvious. This paper is a clinically focused review of the
      literature on osteoporosis related to diabetes mellitus. Due to the different
      pathogenesis of diabetes mellitus type 1 and type 2 it is not surprising that
      there is no uniform entity of diabetic osteopathy. The majority of clinical
      studies in subjects with diabetes mellitus type 1 showed a moderately decreased
      bone mass at the forearm, while bone mass at the femur or lumbar spine was either
      decreased or not different from non-diabetic controls. In patients with diabetes
      mellitus type 2 the risk of osteopenia is not as clear as in type 1 diabetes.
      Bone mineral density at the forearm in patients with type 2 diabetes mellitus was
      decreased, unchanged or even increased in comparison to controls, while bone
      mineral density at the vertebrae or femoral neck was either not significantly
      different or increased, but rarely decreased. The underlying mechanisms
      triggering changes in bone mass in patients with diabetes mellitus type 1 and
      type 2 are not well known. In most studies there was no consistent relationship
      between the metabolic control of diabetes and bone mineral density. Biochemical
      parameters of the calcium and bone metabolism showed no clear relationship to the
      bone mineral density measurements. From few bone histology studies in humans and
      experimental studies there is evidence that a decreased bone formation is one
      major mechanism leading to reduced bone mass in diabetics. Microangiopathy at the
      bone tissue was also discussed as a possible reason for diabetic osteopenia. It
      was shown that insulin and insulin like growth factors (IGF-1, IGF-2) have an
      influence on bone metabolism itself and other growth factors, cytokines and
      hormones may determine changes in diabetic bone metabolism. Recent findings
      suggest that leptin is involved in the regulation of osteoblast function and bone
      mass, which is of special interest in diabetes mellitus type 2. The clinical
      relevance of osteoporosis or osteopenia is determined by the increased risk for
      insufficiency fractures. Few studies found an increased fracture risk, especially
      in older women with type 1 diabetes mellitus, while others did not show an
      increased risk for fractures or even found a decreased rate of fractures in women
      with diabetes mellitus type 2. There is a need for further longitudinal studies,
      including the incidence and risk factors for osteoporotic fractures. In clinical
      routine the extent of diagnostic and therapeutic activities in patients with type
      1 or type 2 diabetes mellitus in respect to generalized bone disease or diabetic
      osteopenia should be based on individual conditions and risk profile for
      osteoporosis.

PMID- 11460596
TI  - The new classification of diabetes mellitus and IGT: a critical approach.
AB  - In 1999 WHO published the new recommendations for diagnostic criteria for
      diabetes. The same publication introduced several new categories including the
      first proposal for diagnostic criteria for the metabolic syndrome. Also, WHO
      established a new category labelled "impaired fasting glycaemia", and thereafter
      this new group and the already established impaired glucose tolerance was
      combined as a common entity labelled "impaired glucose regulation".--These
      recommendations from WHO followed a decision in the American Diabetes Association
      to lower the diagnostic plasma glucose threshold for diabetes in the fasting
      state from 7.8 to 7.0 mmol/l and to use fasting values as the diagnostic test for
      diabetes. The suggested changes in the diagnostic criteria will include a new
      group of individuals as having diabetes, while others may be left undiagnosed if
      fasting glucose values are used as the only diagnostic criteria. The consequence
      of this has been analysed by several groups including the collaborative European
      activity (the DECODE-study).--This review summarises the findings. One major
      problem is that if fasting glucose values are used as the only diagnostic
      criteria in screening for diabetes, approximately one third of the diabetic
      individuals will be left undiagnosed. Furthermore, this group is the group of
      diabetic patients that have the highest mortality from cardiovascular disease and
      stroke, and the group with the worst cardiovascular risk profile compared to
      individuals with elevated fasting glucose values alone. This observation raises
      the need for a continued use of the oral glucose tolerance test in selected
      groups.

PMID- 11460597
TI  - Progress in the characterization of slowly progressive autoimmune diabetes in
      adult patients (LADA or type 1.5 diabetes).
AB  - LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of
      adults and represents a considerable proportion (about 5-10%) of all diabetic
      patients. Associations with high risk HLA genotypes and autoimmune phenomena
      (GAD, IA2, ICA) show similarities with type 1 diabetes, but phenotypical
      characteristics of these patients do not allow the correct identification without
      screening of GAD antibodies. The relatively low antibody titers against islet
      cell antigens in LADA patients may be sign of a less aggressive form of
      autoimmune diabetes and could be responsible for the long non-insulin requirement
      phase of this diabetes type. Similar as in prediabetic relatives of type 1
      diabetic patients the risk for beta cell failure in adult "type 2 diabetic"
      patients increases with the number of antibodies positive. Consequently, low
      titers of GAD--in particular in elderly patients--do not predict a progressive
      and rapid loss of beta-cell failure, when associations with high risk genotypes
      or other islet-cell antibodies are lacking. Patients with LADA share insulin
      resistance with type 2 diabetic patients, but display a more severe defect in
      stimulated beta-cell capacity than patients with classical type 2 diabetes. With
      respect to features of the metabolic syndrome, patients with LADA have lower BMI,
      blood pressure and triglyceride levels compared with classical type 2 diabetes
      patients. Early identification of LADA patients will be mandatory, when effective
      immune interventions are available for prevention of the beta-cell destructive
      process and insulin requirement of these patients.

PMID- 11460598
TI  - [Diagnosis of the gastroesophageal reflux disease: options and criteria].

PMID- 11460599
TI  - [Histological criteria of esophagitis in the gastroesophageal reflux disease.
      Reevaluation of the sensitivity of the esophageal 24-hours pHmetry].
AB  - Little change was observed in the histological criteria of reflux esophagitis
      since the studies of Ismail-Beiji, Pope (1970) and Weinstein (1975). The 24-hour
      esophageal pHmetry has been proposed as a high sensitivity method in diagnosis of
      gastroesophageal reflux disease patients. In this study we selected 35 patients
      with histological esophagitis and submitted them to 24-hour esophageal pHmetry.
      We determined histological differences according to reflux pattern, endoscopic
      esophagitis grades and age. The sensitivity of 24-hour esophageal pHmetry was
      60.0% in our patients. There are higher histological alterations in patients with
      more severe patterns of reflux (supine and combined) and significant difference
      (P < 0.05) in observed quantitative exocytosis between moderate and severe
      endoscopic esophagitis. There are no difference between histological esophagitis
      criteria and age groups.

PMID- 11460600
TI  - [Endoscopic gastrostomy in patients with complicated heart diseases].
AB  - Complicated cardiologic patients with brain ischemia and heart failure need long
      term enteral nutrition. Long term nasoenteral tube feeding may cause
      complications that could be avoided with percutaneous endoscopic gastrostomy. The
      aim of this study was to evaluate the indications for percutaneous endoscopic
      gastrostomy and its main complications. Twelve patients were submitted to
      percutaneous endoscopic gastrostomy (eight male) with main age of 62.42 +/- 22.10
      years old. Brain ischemia was the main indication of percutaneous endoscopic
      gastrostomy and occurred after 35.58 +/- 26.79 days, after initiated enteral
      nutrition. There were no complications during procedure. On late post operatory
      period there were local infection in one cases, treated with local care. In
      conclusion, percutaneous endoscopic gastrostomy is a secure technique with low
      incidence of complications and its indication should be earlier.

PMID- 11460601
TI  - HCV infection in northeastern Brazil: unexpected high prevalence of genotype 3a
      and absence of African genotypes.
AB  - The genomic diversity of HCV embraces 6 genotypes and at least 52 subtypes with
      clinical and epidemiological correlations. There is a paucity of studies
      assessing HCV genotypes and biomolecular epidemiology in Brazil. We studied
      genotype distribution and epidemiological aspects in 232 HCV carriers, 133
      (57.9%) males and 99 (42.1%) females, followed in the liver disease referral unit
      in Salvador, BA, northeastern Brazil. All of them were anti-HCV positive by 3rd
      generation ELISA assay, and HCV-RNA positive by RT-PCR. Genotyping was performed
      by INNOLIPA. Assessment of risk factors for HCV infection showed that 93 (40%)
      had past blood transfusion, 14 (6%) intravenous drug use, 19 (8%) inhalation of
      cocaine, 28 (12%) tattooing, 15 (7%) were health care workers, 5 (2%) had reused
      disposable syringes, 5 (2%) had multiple risk factors and in 53 (23%) no risk
      factor was determined. Genotype 1a was observed in 75 (32%), 1b in 72 (31%), 3a
      in 61 (26%), 2ab in 14 (6%); 5 (2.5%) had mixed genotypes and 5 (2.5%) were
      undetermined. Patients with genotype 1 had a higher mean age (P < 0.05) and no
      particular risk factors were associated with a specific genotype. Genotype 1
      largely predominates in northeast Brazil followed by genotype 3 which, in this
      population, does not seem to be related to intravenous drug abuse, in contrast to
      some European studies. Although 80% of the Salvador population comprises African
      Brazilians, no African genotype was identified, which may mean that HCV was
      introduced into this region via European immigration. This study demonstrated
      some peculiarities of HCV epidemiology in Brazil and strongly suggests that HCV
      introduction to this region was probably related to European immigration.

PMID- 11460602
TI  - [Nutcracker esophagus: clinical evaluation of 97 patients].
AB  - Nutcracker esophagus is a manometric abnormality classified as a primary
      esophageal motor disorder, characterized by high pressure peristaltic waves in
      distal esophagus and related to non-cardiac chest pain. Further studies observed
      nutcracker esophagus in dysphagic patients and recently in gastroesophageal
      reflux disease. However, there is controversy about the meaning of this motor
      disorder and there are few clinical studies involving a great number of patients.
      A retrospective study involving 97 patients with manometric criteria of
      nutcracker esophagus according a control group was undertaken. Most of the
      patients were female (63.9%), mean age 54.3 years. The chief complaint was chest
      pain, followed by dysphagia and heartburn. Clinical findings, as a whole were
      chest pain (53.6%), dysphagia (52.6%), heartburn (52.6%), regurgitation (21.6%),
      otorhinolaryngologic symptoms (15.4%), dyspepsia (15.4%) and odynophagia (4.1%).
      The majority of patients had multiple symptoms, however in 28% just a single one
      was observed. Endoscopic examination observed erosive esophagitis in 8% of the
      patients, while signs of esophageal motor disorders were showed by esophagogram
      in 16.4%. Esophageal pH recordings indicated abnormal gastroesophageal reflux in
      41.2% of the cases reported. We concluded that there are other symptoms in
      nutcracker esophagus patients besides chest pain and dysphagia and the use of
      esophageal pH recordings is helpful to establish its association with acid reflux
      and guide the appropriate therapy.

PMID- 11460603
TI  - Gastric necrosis and perforation as a complication of splenectomy. Case report
      and related references.
AB  - Necrosis of the stomach after isolated splenectomy with the formation of
      gastrocutaneous fistula is a rare event that occurs in less than 1% of
      splenectomies. It is more frequent when the removal of the spleen is done because
      of hematological diseases. Its mortality index can reach 60% and its pathogenesis
      is controversial, as it may be attributed both to direct trauma of the gastric
      wall and to ischemic phenomena. Although the stomach may exhibit exuberant
      arterial blood irrigation, anatomical variations can cause a predisposition
      towards the appearance of potentially ischemic areas, especially after ligation
      of the short gastric vessels around the major curvature of the stomach. Once this
      is diagnosed in the immediate postoperative period, it becomes imperative to
      reoperate. The surgical procedure will depend on the conditions of the peritoneal
      cavity and patient's clinic status. The objective of this study was to report on
      the case of a patient submitted to splenectomy because of closed abdominal
      traumatism, who then presented peritonitis and percutaneous gastric fistula in
      the post-operative period. During the second operation, perforations were
      identified in anterior gastric wall where there had been signs of vascular
      stress. The lesion was sutured after revival of its borders, and the patient had
      good evolution. Prompt diagnosis and immediate treatment of this unusual
      complication are needed to reduce its high mortality rate.

PMID- 11460604
TI  - [Benign recurrent intrahepatic cholestasis: a seven-year follow-up report].
AB  - Benign recurrent intrahepatic cholestasis is a rare autosomal recessive disorder
      characterized by repeated episodes of intense pruritus and jaundice. Patients are
      completely asymptomatic for months to years between symptomatic periods. We
      report a case of a patient with a 7-year history of benign recurrent intrahepatic
      cholestasis. During the follow-up period the patient has suffered three attacks
      of cholestasis, confirmed by biochemical tests and histological exam. Liver
      enzymes were normal between the cholestasis episodes. Despite multiple attacks of
      cholestasis, no permanent liver damage has occurred. Although the diagnosis of
      benign recurrent intrahepatic cholestasis is rare, it should be included in the
      evaluation of a patient with cholestasis. The patients should be reassured of the
      benign course of this disorder.

PMID- 11460605
TI  - [Chronic hepatitis by C virus. Part 2. Treatment].
AB  - Several aspects are revised on the subject related to drugs used, their doses,
      duration of treatment, different responses obtained, according different types of
      diseases and patients studied, as the factors able to modify the results
      obtained.

PMID- 11460606
TI  - Influences of directed research and clinical observations on the development of a
      tartar control whitening dentifrice.
AB  - Early literature described the benefits of cleaning the mouth and teeth to
      prevent tartar accumulation and tooth loss. For more than a century, the need for
      meticulous tooth scaling and regular brushing to maintain oral health has been
      recorded. More recently, because of innovative research into the chemical and
      biological activity of saliva, dentifrices have been formulated which
      specifically interrupt the mineralization of plaque and food debris to stain and
      calculus. Proof of efficacy of these dentifrices are obtained with well-designed
      clinical tests which quantify stain and calculus by using reliable scoring
      systems.

PMID- 11460607
TI  - A calculus clinical study comparing the efficacy of two commercially available
      dentifrices.
AB  - The objective of this double-blind clinical study, conducted in harmony with the
      Volpe-Manhold design for studies of dental calculus, was to compare the effect on
      supragingival calculus formation of a dentifrice containing pyrophosphate,
      tripolyphosphate and a copolymer in a 0.243% sodium fluoride/silica base (Test
      Dentifrice), to that of a commercially available calculus-inhibiting dentifrice
      containing tetrapotassium pyrophosphate, disodium pyrophosphate, and tetrasodium
      pyrophosphate in a 0.243% sodium fluoride/silica base (Positive Control
      Dentifrice). Adult male and female subjects from the Northern New Jersey area
      were entered into the study, provided a full oral prophylaxis and assigned the
      use of a placebo (non-calculus-inhibiting) dentifrice for eight weeks. At the
      completion of this initial period, subjects were assessed for baseline Volpe
      Manhold Calculus Index scores, provided another full prophylaxis and stratified
      into two treatment groups which were balanced for age, sex and baseline calculus.
      Subjects were instructed to brush their teeth twice daily (morning and evening)
      for one minute with their assigned dentifrice, using a soft-bristled toothbrush.
      Examinations for dental calculus were again performed after twelve weeks' use of
      the study dentifrices. Eighty-nine (89) subjects complied with the protocol and
      completed the entire study. At the three-month examination, the Test Dentifrice
      group exhibited a statistically significant 31.0% reduction in the mean Volpe
      Manhold Calculus Index score compared to the Positive Control Dentifrice group.
      The results of this clinical study support the conclusion that a new calculus
      inhibiting dentifrice containing pyrophosphate, tripolyphosphate, and a copolymer
      in a 0.243% sodium fluoride/silica base is efficacious for the control of the
      development of supragingival calculus, and provides a level of benefit greater
      than that provided by a commercially available calculus-inhibiting dentifrice
      containing tetrapotassium pyrophosphate, disodium pyrophosphate, and tetrasodium
      pyrophosphate in a 0.243% sodium fluoride/silica base.

PMID- 11460608
TI  - A clinical comparison of two calculus-inhibiting dentifrices.
AB  - The objective of this double-blind clinical study, conducted in harmony with the
      Volpe-Manhold design for studies of dental calculus, was to compare the effect on
      supragingival calculus formation of a dentifrice containing pyrophosphate,
      tripolyphosphate and a copolymer in a 0.243% sodium fluoride/silica base (Test
      Dentifrice), to that of a commercially available calculus-inhibiting dentifrice
      containing tetrapotassium pyrophosphate, disodium pyrophosphate and tetrasodium
      pyrophosphate in a 0.243% sodium fluoride/silica base (Positive Control
      Dentifrice). Adult male and female subjects from the Buffalo, New York area were
      entered into the study, provided a full oral prophylaxis, and assigned the use of
      a placebo (non-calculus-inhibiting) dentifrice for fourteen weeks. At the
      completion of this initial period, subjects were assessed for baseline Volpe
      Manhold Calculus Index scores, provided another full prophylaxis, and stratified
      into two treatment groups which were balanced for age, sex and baseline calculus.
      Subjects were instructed to brush their teeth twice daily (morning and evening)
      for one minute with their assigned dentifrice, using a soft-bristled toothbrush.
      Examinations for dental calculus were again performed after twelve weeks' use of
      the study dentifrices. Ninety-one (91) subjects complied with the protocol and
      completed the entire study. At the three-month examination, the Test Dentifrice
      group exhibited a statistically significant 27.3% reduction in mean Volpe-Manhold
      Calculus Index score as compared to the Positive Control Dentifrice group. The
      results of this clinical study support the conclusion that a new calculus
      inhibiting dentifrice, containing pyrophosphate, tripolyphosphate and a copolymer
      in a 0.243% sodium fluoride/silica base, is efficacious for the control of the
      development of supragingival calculus, and provides a level of benefit greater
      than that provided by a commercially available calculus-inhibiting dentifrice
      containing tetrapotassium pyrophosphate, disodium pyrophosphate and tetrasodium
      pyrophosphate in a 0.243% sodium fluoride/silica base.

PMID- 11460609
TI  - A twelve-week clinical comparison of two tartar control dentifrices.
AB  - The objective of this double-blind clinical study, conducted using the Volpe
      Manhold evaluation method for dental calculus, was to compare the effect on
      supragingival calculus formation of a dentifrice containing tetrasodium
      pyrophosphate, sodium tripolyphosphate, and a copolymer in a 0.243% sodium
      fluoride/silica base (Test Dentifrice), to that of a commercially available
      calculus-inhibiting dentifrice containing tetrasodium pyrophosphate and a
      copolymer in a 0.243% sodium fluoride/silica base (Positive Control Dentifrice).
      Adult male and female subjects from the northern New Jersey area were entered
      into the study based on a pre-test (baseline) Volpe-Manhold Calculus Index score
      of 7.0 or greater, provided a full oral prophylaxis, and stratified into two
      treatment groups which were balanced for age, sex and baseline calculus scores.
      Subjects were instructed to brush their teeth twice daily (morning and evening)
      for one minute with their assigned dentifrice, using a soft-bristled toothbrush.
      Examinations for dental calculus were again performed after twelve weeks' use of
      the study dentifrices. Seventy-three (73) subjects complied with the protocol,
      and completed the entire study. At the twelve-week examination, the Test
      Dentifrice group exhibited a statistically significant 43.5% reduction in mean
      Volpe-Manhold Calculus Index scores compared to the Positive Control Dentifrice
      group. The results of this clinical study support the conclusion that a new
      calculus-inhibiting dentifrice, containing tetrasodium pyrophosphate, sodium
      tripolyphosphate, and a copolymer in a 0.243% sodium fluoride/silica base, is
      efficacious for the control of the development of supragingival calculus, and
      provides a level of benefit greater than that provided by a commercially
      available calculus-inhibiting dentifrice containing tetrasodium pyrophosphate and
      a copolymer in a 0.243% sodium fluoride/silica base.

PMID- 11460611
TI  - A six-week clinical tooth whitening study of a new calculus-inhibiting dentifrice
      formulation.
AB  - This six-week double-blind clinical study compared the toothwhitening effects of
      a new calculus-inhibiting dentifrice containing pyrophosphate, tripolyphosphate
      and copolymer in a 0.243 sodium fluoride/silica base (Test Dentifrice) with two
      commercially available dentifrices: Aquafresh Whitening Toothpaste with Fluoride
      and Crest Regular Fluoride Toothpaste. After a baseline examination for extrinsic
      tooth stain, qualifying adult males and females from Manchester, United Kingdom
      and from Mississauga, Ontario, Canada were randomly assigned into three test
      groups. Each group was balanced for gender, tobacco habits and levels of tooth
      stain. Subjects were to brush their teeth twice daily with a soft-bristled
      toothbrush using the assigned toothpaste. One-hundred and twenty-eight (128)
      subjects complied with instructions and completed the trial. Subjects using the
      Test Dentifrice exhibited statistically less stain area and less stain intensity
      than did either the Aquafresh or Crest groups. Crest Regular Fluoride toothpaste
      was statistically less effective than Aquafresh Whitening toothpaste in removing
      stain. Results in this trial support the conclusion that a new dentifrice
      formulation containing pyrophosphate, tripolyphosphate and a copolymer, in a
      0.243% sodium fluoride/silica base, effectively removes extrinsic tooth stain.

PMID- 11460612
TI  - Brownfields: a case study in partnering with residents to develop an easy-to-read
      print guide.
AB  - At least three cultural circumstances have converged to make environmental health
      information critical, yet highly inaccessible, to many Americans: 1) the
      declining literacy levels of almost half the population, 2) the growing cultural
      diversity of the population, and 3) the complexity of environmental health
      information and science. This paper presents a case study of how literacy experts
      and environmental scientists partnered with a panel of inner-city residents to
      produce a community guide about brownfields, a process the authors refer to as
      "cooperative composing." The goal was to create low-barrier material (fifth
      through-eight-grade reading level) that would inform people about brownfields
      issues so that they can meaningfully insert themselves into the process of
      planning for brownfields reuse and redevelopment. The authors structured an
      ongoing process with a panel of residents to learn with them just what types of
      information they wanted and what language level and graphics were appropriate. A
      primary motivator of this study was the belief that informed, activated residents
      will bring about greater equity and collaboration in environmental planning for
      brownfields.

PMID- 11460613
TI  - The challenges of installing innovative treatment in small water systems.
AB  - The Drinking Water Assistance Program of the Montana Water Center sponsors the
      piloting of innovative treatment technologies and approaches to aid small public
      water systems. Now in its fifth year, the program has sponsored demonstrations at
      more than 20 systems around the United States. Project personnel have encountered
      numerous challenges in installing and testing innovative treatment methods. Many
      of the challenges arise when treatment is added to a system that previously had
      none, or to a system that used only chlorination. Some of the difficulties
      involve system engineering, some are people problems, others take the form of
      business or regulatory impediments. The purpose of this paper is to share some of
      the more important lessons that have been learned in fostering the adoption of
      innovative treatment. Examples are drawn from projects concerned with corrosion
      control, nitrate reduction, microfiltration, and disinfection.

PMID- 11460614
TI  - Oven mitts as a vehicle for cross-contamination in commercial food service
      establishments.

PMID- 11460615
TI  - Public agencies--authority and responsibilities.

PMID- 11460616
TI  - The long-forgotten refractometer.

PMID- 11460617
TI  - Drinking water and disease: how big is the problem?

PMID- 11460618
TI  - Brownfields and other distressed communities: assessing neighborhood
      characteristics.

PMID- 11460619
TI  - Occupational and community noise.

PMID- 11460620
TI  - Rapid determination of bacteria in pools.
AB  - If a method for rapid determination of bacterial levels in swimming pools and
      whirlpools were available, bacterial health risks could be avoided before
      exposure occurred. Such a method would enable public-health authorities to make
      timely decisions about closing or reopening pools and to adjust disinfectant
      doses. The purpose of this study was to determine if a rapid adenosine
      triphosphate (ATP) bioluminescence method would serve this purpose.
      Bacteriological analyses were completed on samples from swimming pools and
      whirlpools in Washtenaw County, Michigan. The results from the ATP assay were
      compared with those from the conventional plate count method and were found to be
      highly correlated (r = .92). To assess whether a prefiltration step was necessary
      to delete nonbacterial ATP--which might originate from bathers' skin cells or
      other debris--two procedures were tested: one with prefiltration and one without
      prefiltration. The results for prefiltered samples were not statistically
      different from the results for non-prefiltered samples (p > .05), for both the
      heterotrophic plate counts and the ATP bioluminescence method. This study
      indicates that the ATP assay can estimate bacterial levels in pools within
      minutes and without prefiltration.

PMID- 11460621
TI  - Secondary flows in axial turbines--a review.
AB  - An important problem that arises in the design and the performance of axial flow
      turbines is the understanding, analysis, prediction and control of secondary
      flows. Sieverding has given a review of secondary flow literature, covering up to
      1985. In this paper a brief review of pre-1985 work is given, and then a survey
      of open literature secondary flow investigations since the Sieverding review is
      presented. Most of the studies reviewed deal with plane or annular cascade flows.
      Tip clearance effects are not covered. The basic secondary flow picture for a
      turbine cascade, as measured and verified by a number of investigators is
      described. Recent work that shows refined secondary flow vortex structures is
      examined. A flow parameter based on inlet boundary layer properties used to
      predict horseshoe vortex swirl is presented. Work on secondary flow loss
      reduction, involving airfoil geometry, endwall fences and endwall contouring is
      briefly reviewed. A new leading edge bulb geometry that has demonstrated
      impressive loss reduction is considered. It is concluded that accurate routine
      prediction of secondary flow losses has not yet been achieved, and must await
      either a better turbulence model or more experiments to reveal new endwall loss
      production mechanisms. Lastly, loss is examined from the standpoint of entropy
      generation.

PMID- 11460623
TI  - Film colling: what did we learn from our measurements?

PMID- 11460622
TI  - Flow and heat transfer predictions for film cooling.
AB  - Film cooling flows are characterized by a row of jets injected at an angle from
      the blade surface or endwalls into the heated crossflow. The resulting flowfield
      is quite complex, and accurate predictions of the flow and heat transfer have
      been difficult to obtain, particularly in the near field of the injected jet. The
      flowfield is characterized by a spectrum of vortical structures including the
      dominant kidney vortex, the horse-shoe vortex, the wake vortices and the shear
      layer vortices. These anisotropic and unsteady structures are not well
      represented by empirical or ad-hoc turbulence models, and lead to inaccurate
      predictions in the near field of the jet. In this paper, a variety of modeling
      approaches have been reviewed, and the limitations of these approaches are
      identified. Recent emergence of Direct Numerical Simulation (DNS) and Large Eddy
      Simulation (LES) tools allow the resolution of the coherent structure dynamics,
      and it is shown in this paper, that such approaches provide improved predictions
      over that obtained with turbulence models.

PMID- 11460624
TI  - Combustor liner cooling technology in scope of reduced pollutant formation and
      rising thermal efficiencies.

PMID- 11460625
TI  - Jet-impingement heat transfer in gas turbine systems.
AB  - A review of jet-impingement heat transfer in gas turbine systems is presented.
      Characteristics of the different flow regions for submerged jets--free jet,
      stagnation flow, and wall jet--are reviewed. Heat transfer characteristics of
      both single and multiple jets are discussed with consideration of the effects of
      important parameters relevant to gas turbine systems including curvature of
      surfaces, crossflow, angle of impact, and rotation.

PMID- 11460626
TI  - Recent developments in turbine blade internal cooling.
AB  - This paper focuses on turbine blade internal cooling. Internal cooling is
      achieved by passing the coolant through several rib-enhanced serpentine passages
      inside the blade and extracting the heat from the outside of the blades. Both jet
      impingement and pin-fin-cooling are also used as a method of internal cooling. In
      the past number of years there has been considerable progress in turbine blade
      internal cooling research and this paper is limited to reviewing a few selected
      publications to reflect recent developments in turbine blade internal cooling.

PMID- 11460627
TI  - Heat transfer technology for internal passages of air-cooled blades for heavy
      duty gas turbines.
AB  - The present review paper, although far from being complete, aims to give an
      overview about the present state of the art in the field of heat transfer
      technology for internal cooling of gas turbine blades. After showing some typical
      modern cooled blades, the different methods to enhance heat transfer in the
      internal passages of air-cooled blades are discussed. The complicated flows
      occurring in bends are described in detail, because of their increasing
      importance for modern cooling designs. A short review about testing of cooling
      design elements is given, showing the interaction of the different cooling
      features as well. The special focus of the present review has been put on the
      cooling of blades for heavy-duty gas turbines, which show several differences
      compared to aero-engine blades.

PMID- 11460628
TI  - Cooling systems for ultra-high temperature turbines.
AB  - This paper describes an introduction of research and development activities on
      steam cooling in gas turbines at elevated temperature of 1500 C and 1700 C level,
      partially including those on water cooling. Descriptions of a new cooling system
      that employs heat pipes are also made. From the view point of heat transfer, its
      promising applicability is shown with experimental data and engine performance
      numerical evaluation.

PMID- 11460629
TI  - Some current research in rotating-disc systems.
AB  - Rotating-disc systems are used to model the flow and heat transfer that occurs
      inside the cooling-air systems of gas-turbine engines. In this paper, recent
      computational and experimental research in three systems is discussed: rotor
      stator systems, rotating cavities with superposed flow and buoyancy-induced flow
      in a rotating cavity. Discussion of the first two systems concentrates
      respectively on pre-swirl systems and rotating cavities with a peripheral inflow
      and outflow of cooling air. Buoyancy-induced flow in a rotating cavity is one of
      the most difficult problems facing computationalists and experimentalists, and
      there are similarities between the circulation in the Earth's atmosphere and the
      flow inside gas-turbine rotors. For this case, results are presented for heat
      transfer in sealed annuli and in rotating cavities with an axial throughflow of
      cooling air.

PMID- 11460630
TI  - Selection of a turbine cooling system applying multi-disciplinary design
      considerations.
AB  - The presented paper describes a multi-disciplinary cooling selection approach
      applied to major gas turbine engine hot section components, including turbine
      nozzles, blades, discs, combustors and support structures, which maintain blade
      tip clearances. The paper demonstrates benefits of close interaction between
      participating disciplines starting from early phases of the hot section
      development. The approach targets advancements in engine performance and cost by
      optimizing the design process, often requiring compromises within individual
      disciplines.

PMID- 11460631
TI  - Analysis of particle laden flow and heat transfer in cascade and rocket nozzle.
AB  - This paper presents results for the calculation of particle trajectories in a
      cascade and a rocket nozzle using a Lagrangian method. When the floating
      particles collide to the components, the component surface is damaged severely.
      The surface erosion rate is strongly dependent on a particle size, a particle
      impact angle and a surface material. For a compressor cascade, the particle
      impact rate increases proportionally with the flow inlet angle and the erosion
      rate on the pressure side surface of blade are related to the surface or coating
      materials. For a solid rocket nozzle, the particle free zone in the nozzle
      divergent section increases quickly with increasing particle size and the maximum
      heat transfer density occurs at the starting region of nozzle convergent section.
      The Al2O3 droplet breaks up around the nozzle throat due to the high velocity
      difference between the droplet and gas stream, resulting in the big change of
      particle free zone.

PMID- 11460632
TI  - Convective heat transfer on an inlet guide vane.
AB  - The flow and temperature fields around an inlet guide vane are determined
      numerically by a CFD method. Outer surface temperatures, heat transfer
      coefficient distributions, and static pressure distributions are presented. Three
      different thermal boundary conditions on the vane are analysed. The computed
      results are compared with experimental data. The governing equations are solved
      by a finite-volume method with the low Reynolds number version of the k-omega
      turbulence model by Wilcox implemented. It is found that the calculated results
      agree best with measurements if a conjugate heat transfer approach is applied and
      thus this wall condition is recommended for future investigations of film cooling
      of guide vanes and turbine blades.

PMID- 11460633
TI  - Effect of Reynolds number, turbulence level and periodic wake flow on heat
      transfer on low pressure turbine blades.
AB  - The development of effective cooling methods is of major importance for the
      design of new gas turbines blades. The conception of optimal cooling schemes
      requires a detailed knowledge of the heat transfer processes on the blade's
      surfaces. The thermal load of turbine blades is predominantly determined by
      convective heat transfer which is described by the local heat transfer
      coefficient. Heat transfer is closely related to the boundary layer development
      along the blade surface and hence depends on various flow conditions and
      geometrical parameters. Particularly Reynolds number, pressures gradient and
      turbulence level have great impact on the boundary layer development and the
      according heat transfer. Therefore, in the present study, the influence of
      Reynolds number, turbulence intensity, and periodic unsteady inflow on the local
      heat transfer of a typical low pressure turbine airfoil is experimentally
      examined in a plane cascade.

PMID- 11460634
TI  - Surface temperature mapping of gas turbine blading by means of high resolution
      pyrometry.

PMID- 11460635
TI  - Studies on free stream turbulence as related to gas turbine heat transfer. A
      review of authors' past work and future implications.
AB  - A review of the past work done on free stream turbulence (FST) as applied to gas
      turbine heat transfer and its implications for future studies are presented. It
      is a comprehensive approach to the results of many individual studies in order to
      derive the general conclusions that could be inferred from all rather than
      discussing the results of each individual study. Three experimental and four
      modeling studies are reviewed. The first study was on prediction of heat transfer
      for film cooled gas turbine blades. An injection model was devised and used along
      with a 2-D low Reynolds number k-epsilon model of turbulence for the
      calculations. Reasonable predictions of heat transfer coefficients were obtained
      for turbulence intensity levels up to 7%. Following this modeling study a series
      of experimental studies were undertaken. The objective of these studies was to
      gain a fundamental understanding of mechanisms through which FST augments the
      surface heat transfer. Experiments were carried out in the boundary layer and in
      the free stream downstream of a gas turbine combustor simulator, which produced
      initial FST levels of 25.7% and large length scales (About 5-10 cm for a boundary
      layer 4-5 cm thick). This result showed that one possible mechanism through which
      FST caused an increase in heat transfer is by increasing the number of ejection
      events. In a number of modeling studies several well-known k-epsilon models were
      compared for their predictive capability of heat transfer and skin friction
      coefficients under moderate and high FST. Two data sets, one with moderate levels
      of FST (about 7%) and one with high levels of FST (about 25%) were used for this
      purpose. Although the models did fine in their predictions of cases with no FST
      (baseline cases) they failed one by one as FST levels were increased. Under high
      FST (25.7% initial intensity) predictions of Stanton number were between 35-100%
      in error compared to the measured values. Later a new additional production term
      indicating the interaction between the turbulent kinetic energy (TKE) and mean
      velocity gradients was introduced into the TKE equation. The predicted results of
      skin friction coefficient and Stanton number were excellent both in moderate and
      high FST cases. In fact these model also gave good predictions of TKE profiles
      whereas earlier unmodified models did not predict the correct TKE profiles even
      under moderate turbulence intensities. Although this new production term seems to
      achieve the purpose, it is the authors' belief that it is diffusion term of the
      TKE equation, which needs to be modified in order to fit the physical events in
      high FST boundary layer flows. The results of these studies are currently being
      used to come up with new diffusion model for the TKE equation.

PMID- 11460636
TI  - Heat transfer near turbine nozzle endwall.
AB  - This paper gives an overview and reviews recent findings concerning turbine
      endwall cooling in the literature. The text below begins with a brief discussion
      of the secondary flows and heat transfer around cascade endwall. This will be
      followed by a review of recent developments in cooling concepts and related heat
      transfer results. Key topics include: film cooling, upstream bleeding, endwall
      contouring, and leakage through component interfaces.

PMID- 11460637
TI  - A conjugate heat transfer procedure for gas turbine blades.
AB  - A conjugate heat transfer procedure, allowing for the use of different solvers on
      the solid and fluid domain(s), is presented. Information exchange between solid
      and fluid solution is limited to boundary condition values, and this exchange is
      carried out at any pseudo-time step. Global convergence rate of the procedure is,
      thus, of the same order of magnitude of stand-alone computations.

PMID- 11460638
TI  - Heat/mass transfer characteristics on turbine shroud with blade tip clearance.

PMID- 11460639
TI  - Heat transfer and flow characteristics on a gas turbine shroud.
AB  - The work described in this paper is an experimental investigation of the heat
      transfer from the main flow to a turbine shroud surface, which may be applicable
      to ceramic gas turbines. Three kinds of turbine shrouds are considered with a
      flat surface, a taper surface and a spiral groove surface opposite to the blades
      in an axial flow turbine of actual turbo-charger. Heat transfer measurements were
      performed for the experimental conditions of a uniform heat flux or a uniform
      wall temperature. The effects of the inlet flow angle, rotational speed, and tip
      clearance on the heat transfer coefficient were clarified under on- and off
      design flow conditions. The mean heat transfer coefficient was correlated to the
      blade Reynolds number and tip clearance, and compared with an experimental
      correlation and measurements of a flat surface. A comparison was also made for
      the measurement of static pressure distributions.

PMID- 11460640
TI  - A novel digital image processing system for the transient liquid crystal
      technique applied for heat transfer and film cooling measurements.
AB  - This paper is dedicated to the transient liquid crystal technique measurements
      for multiple view access by using a novel digital recording and image processing
      system. The transient liquid crystal technique is widely used for heat transfer
      investigations in turbomachinery. It has been applied in our laboratory in
      several test facilities such as a linear cascade for external film cooling
      measurements or on a ribbed squared duct for internal cooling measurements. The
      data analysis as well as the measurement equipment is described, with a special
      focus on the newly developed computerized image processing system suitable to
      capture the liquid crystal signal.

PMID- 11460641
TI  - Contribution of heat transfer to turbine blades and vanes for high temperature
      industrial gas turbines. Part 1: Film cooling.
AB  - This paper deals with the contribution of heat transfer to increase the turbine
      inlet temperature of industrial gas turbines in order to attain efficient and
      environmentally benign engines. High efficiency film cooling, in the form of
      shaped film cooling and full coverage film cooling, is one of the most important
      cooling technologies. Corresponding heat transfer tests to optimize the film
      cooling effectiveness are shown and discussed in this first part of the
      contribution.

PMID- 11460642
TI  - Experimental investigation of film cooling flow induced by shaped holes on a
      turbine blade.
AB  - The present study is the second half of a piece of work carried out in
      collaboration with SNECMA. It investigates shaped hole film cooling, numerically
      and experimentally. The aim of this paper is the experimental analysis of shaped
      hole film cooling on a large scale turbine blade (1.4 m chord). The test section
      is a large scale turbine inlet guide vane cascade. The test airfoil is equipped
      with a row of nine 50 degrees sloped shaped holes. They are located on the
      suction side at 20% of the curvilinear length of the blade from the stagnation
      point. The inlet film cooling hole diameter is 12 mm. The jet flow is heated to
      55 degrees C above the crossflow temperature. Velocity and temperature field
      measurements have been done to obtain mean and fluctuating values. The results
      are compared to those obtained by Beral on the same experimental apparatus and in
      the same test conditions, for a row of cylindrical holes.

PMID- 11460643
TI  - Film cooling from rows of holes--effect of cooling hole shape and row arrangement
      on adiabatic effectiveness.
AB  - In the present study the film cooling performance in terms of the adiabatic film
      cooling effectiveness on the scaled suction side model of an actual guide vane
      was investigated. An infrared thermography measurement system was used to
      determine highly resolved distribution of models surface temperature. Two
      different film cooling hole configurations were investigated: a single row of
      fanshaped holes and a double row of cylindrical holes in staggered arrangement.
      The influence of blowing rate and mainstream turbulence level on effectiveness
      was investigated in a wide range for both of the injection configurations.

PMID- 11460644
TI  - Effects of bulk flow pulsations on film cooling with shaped holes.
AB  - Experimental results are presented which describe the effects of bulk flow
      pulsations on injectant behavior and film cooling performance around shaped holes
      with compound angle orientations. The shaped holes have a 15 degrees forward
      expansion with an inclination angle of 35 degrees. The orientation angles
      considered are 0 degree, 30 degrees, and 60 degrees. The pulsation frequency is
      fixed at 32 Hz, but changes in the time-averaged blowing ratios of 0.5, 1.0, and
      2.0 produce three different coolant Strouhal numbers. Flow visualization shows
      that bulk flow pulsations cause significant periodic variations of the injectant
      flow rate, and produce severe crossflow ingestion at a high coolant Strouhal
      number. Although shaped holes show improved film coverage compared to round holes
      under steady condition, shaped holes are so sensitive to flow pulsations that a
      drastic reduction in the film cooling performance is observed at a high coolant
      Strouhal number.

PMID- 11460645
TI  - Film cooling: case of double rows of staggered jets.
AB  - An experimental investigation of film cooling of a wall in a case of double rows
      of staggered hot jets (65 degrees C) in an ambient air flow. The wall is heated
      at a temperature value between the one of the jets and the one of the main flow.
      Experiments have been carried out for different injection rates, the main flow
      velocity is maintained at 32 m/s. Association of the measures of temperature
      profiles by cold wire and the measures of wall temperature by infrared
      thermography allows us to describe the behaviour of the flows and to propose the
      best injection which assures a good cooling of the plate.

PMID- 11460646
TI  - Characteristics of various film cooling jets injected in a conduit.
AB  - In the present study, film cooling characteristics by the jets through various
      easy-to-make straight holes and slots have been investigated. In this experiment,
      seven kinds of injection geometries were used. They were circular, rectangular,
      elliptic and oval holes and slots, respectively.

PMID- 11460647
TI  - Film cooling performance on curved walls with compound angle hole configuration.
AB  - In order to explore the effect of compound angle holes on film cooling over a
      convex wall and a concave wall, the present study adopts the transient liquid
      crystal thermography for conducting the film cooling measurement on simple hole
      and expanded-hole configurations. Two compound angles of 0 and 45 deg are tested
      at an elevated mainstream turbulence condition (Tu) of 3.8%. The test pieces have
      the different radius of curvature (2r/D) of 92.5 on convex and 86.5 on concave,
      and the same pitch to diameter ratio (P/D) of 3 on both convex and concave walls.
      All measurements were conducted under the mainstream Reynolds number (Re(d)) of
      1700 on convex and 2300 on concave with the density ratio between coolant and
      mainstream (rho c/rho m) of 0.98. In current study, the effect of blowing ratio
      (M) on film cooling performance is investigated by varying the range of blowing
      ratio from 0.5 and 2.0. The present measured results show that the forward
      expanded hole injection provides better surface protection than the simple hole
      injection. As far as the injection angle is concerned, compound angle injection
      provides higher film effectiveness than simple angle injection. However, the
      forward-expanded hole in injection (beta = 0 degree) has the best performance on
      both convex and concave surfaces.

PMID- 11460648
TI  - The variation of heat transfer coefficient, adiabatic effectiveness and
      aerodynamic loss with film cooling hole shape.
AB  - The heat transfer coefficient and adiabatic effectiveness of cylindrical, fan
      shaped holes and a slot are presented for the region zero to 50 diameters
      downstream of the holes. Narrow-band liquid crystals were used on a heated flat
      plate with heated air coolant. These parameters have been measured in a steady
      state, low speed facility at engine representative Reynolds number based on hole
      diameter and pressure difference ratio (ideal momentum flux ratio). The
      aerodynamic loss due to each of the film cooling geometries has been measured
      using a traverse of the boundary layer far downstream of the film cooling holes.
      Compared to the cylindrical holes, the fan shaped hole case showed an improvement
      in the uniformity of cooling downstream of the holes and in the level of
      laterally averaged film cooling effectiveness. The fan effectiveness approached
      the slot level and both the fan and cylindrical hole cases show lower heat
      transfer coefficients than the slot and non film cooled cases based on the
      laterally averaged results. The drawback to the fan shaped hole was that the
      aerodynamic loss was significantly higher than both the slot and cylindrical hole
      values due to inefficient diffusion in the hole exit expansion.

PMID- 11460649
TI  - Numerical investigation of film cooling flow induced by cylindrical and shaped
      holes.
AB  - The present study is the second half of a two part work carried out in
      collaboration with SNECMA which tends to investigate a shaped hole film cooling
      experimentally and numerically. The aim of this paper is the numerical study of
      3D phenomena induced by cylindrical and shaped hole film cooling on a flat wall.
      The two calculations show up classical structures such as horseshoe or kidney
      vortices and their differences according to the shape configuration. A detailed
      study demonstrates their influence on the jet behaviour. Comparing both cases
      reveals the impact of shaping on the velocity field and vortex motions. The
      calculations were performed by resolving the 3D Navier-Stokes equations
      associated with a k-epsilon turbulence model. The solver is the CANARI code
      developed by ONERA.

PMID- 11460650
TI  - Transition to turbulence under low-pressure turbine conditions.
AB  - In this paper, the topic of laminar to turbulent flow transition, as applied to
      the design of gas turbines, is discussed. Transition comes about when a flow
      becomes sufficiently unstable that the orderly vorticity structure of the laminar
      layer becomes randomly oriented. Vorticity with a streamwise component leads to
      rapid growth of eddies of a wide range of sizes and eventually to turbulent flow.
      Under "natural" transition, infinitesimal disturbances of selected frequencies
      grow. "Bypass transition" is a term coined to describe a similar process, but one
      driven by strong external disturbances. Transition proceeds so rapidly that the
      processes associated with "natural" transition seem to be "bypassed." Because the
      flow environment in the turbine is disturbed by wakes from upstream airfoils,
      eddies from combustor flows, jets from film cooling, separation zones on upstream
      airfoils and steps in the duct walls, transition is of the bypass mode. In this
      paper, we discuss work that has been done to characterize and model bypass
      transition, as applied to the turbine environment.

PMID- 11460651
TI  - Numerical investigation of heat transfer on film-cooled turbine blades.
AB  - The accurate heat transfer prediction of film-cooled blades is a key issue for
      the aerothermal turbine design. For this purpose, advanced numerical methods have
      been developed at Snecma Moteurs. The goal of this paper is the assessment of a
      three-dimensional Navier-Stokes solver, based on the ONERA CANARI-COMET code,
      devoted to the steady aerothermal computations of film-cooled blades. The code
      uses a multidomain approach to discretize the blade to blade channel with
      overlapping structured meshes for the injection holes. The turbulence closure is
      done by means of either Michel mixing length model or Spalart-Allmaras one
      transport equation model. Computations of thin 3D slices of three film-cooled
      nozzle guide vane blades with multiple injections are performed. Aerothermal
      predictions are compared to experiments carried out by the von Karman Institute.
      The behavior of the turbulence models is discussed, and velocity and temperature
      injection profiles are investigated.

PMID- 11460652
TI  - Comparison between two models of cooling surfaces using blowing.
AB  - To protect surfaces against high temperatures, the blowing through a porous
      material is studied. The geometry is that of a circular cylinder in cross-flow
      and the effectiveness of the blowing for the thermal protection is numerically
      investigated. Two models are developed for the blowing simulation and comparisons
      are made with experimental data obtained in a heated wind-tunnel. It is shown
      that the blowing strongly affects the dynamical and thermal profiles over the
      surface, thickening the boundary layers and decreasing the external transfer
      coefficients. It results in a lower viscous drag and thermal stress. The wall
      temperature dramatically decreases with blowing and the heat flux is also
      affected.

PMID- 11460653
TI  - Finite element analysis of flowfield in the single hole film cooling technique.
AB  - Film cooling is currently used in gas turbine hot sections, such as the combustor
      wall and the turbine blades, to prevent those sections from failing at elevated
      temperatures. In the single hole film cooling method, coolant air is injected
      from a hole into the mainstream and thus the flow is naturally three dimensional.
      In this paper, the Navier-Stokes and the energy equations are solved on a flat
      plate by the Finite Element Method (FEM) using brick elements. Algebraic
      equations are obtained by use of the Petrov-Galerkin method. The pressure term is
      removed from the momentum equations, by employing the Penalty method. The
      governing equations are transient and the flow is incompressible and turbulent.
      The model of turbulence in the near wall region is the wall function method, and
      in the fully turbulent region is the k-epsilon model. The system of the algebraic
      equations are solved by the Frontal method. The coolant injection angle and the
      blowing rate are among the parameters which are studied. In order to examine the
      present computer code, the results are compared with the Blasius (exact) solution
      and also with the empirical 1/7th power-law and good agreement is shown. Also,
      the optimum cooling performance is shown to be at 35 degree angle of coolant
      injection and the optimum blowing rate is 0.5. The film cooling effectiveness
      data, at the optimum conditions, is directly compared with the experimental
      results of Goldstein et al. and good agreement is demonstrated.

PMID- 11460654
TI  - Effects of entrance crossflow directions to film cooling holes.
AB  - Two-dimensional distributions of local adiabatic film cooling effectiveness as
      well as discharge coefficients have been measured to investigate the effect of
      different entrance crossflow orientations and magnitudes on film-cooling
      performance. Operating conditions have been varied in terms of hot gas Mach
      number (up to 0.6), coolant crossflow Mach number (up to 0.6), coolant crossflow
      orientation (perpendicular or parallel with respect to the mainflow), and blowing
      ratio (0.5-1.5). The temperature ratio of coolant and hot gas was kept constant
      at 0.56 for the effectiveness tests, leading to an enginelike density ratio of
      1.8. Infrared thermography was applied to perform local measurements of the
      surface temperatures with high resolution. The results indicate that the impact
      of hot gas crossflow Mach number is not very pronounced within the range of Mach
      numbers investigated. In contrast to this finding, the effect of internal coolant
      crossflow is very pronounced and strongly depends on coolant crossflow
      orientation and the ejected mass flow rate.

PMID- 11460655
TI  - Mach number effect on jet impingement heat transfer.
AB  - An experimental investigation of heat transfer from a single round free jet,
      impinging normally on a flat plate is described. Flow at the exit plane of the
      jet is fully developed and the total temperature of the jet is equal to the
      ambient temperature. Infrared measurements lead to the characterization of the
      local and averaged heat transfer coefficients and Nusselt numbers over the
      impingement plate. The adiabatic wall temperature is introduced as the reference
      temperature for heat transfer coefficient calculation. Various nozzle diameters
      from 3 mm to 15 mm are used to make the injection Mach number M vary whereas the
      Reynolds number Re is kept constant. Thus the Mach number influence on jet
      impingement heat transfer can be directly evaluated. Experiments have been
      carried out for 4 nozzle diameters, for 3 different nozzle-to-target distances,
      with Reynolds number ranging from 7200 to 71,500 and Mach number from 0.02 to
      0.69. A correlation is obtained from the data for the average Nusselt number.

PMID- 11460656
TI  - Numerical investigation of combined impingement and convection heat transfer.
AB  - This paper concerns development of a prediction method for combined turbulent
      impingement and convection heat transfer. Firstly, a prediction of a single round
      unconfined impinging air jet without crossflow is investigated to assess the
      performance of linear and non-linear two-equation turbulence models. The results
      show that realizable and/or non-linear two-equation models may successfully be
      used for impinging jet heat transfer predictions but there are significant
      differences between the formulations. Among the models tested, a non-linear k
      omega showed superior performance. Secondly, the influence of crossflow is
      considered and a plane confined air jet is investigated. For this case the models
      based on a frequency-equation (omega) show quite different and more reasonable
      predictions compared to the dissipation-equation (epsilon) based models.

PMID- 11460657
TI  - Mass/heat transfer in dimpled two-pass coolant passages with rotation.
AB  - Mass/heat transfer measurements are made in dimpled (hemispherical depressions)
      inlet and outlet coolant flow passages using the naphthalene sublimation method.
      The leading and trailing surfaces are dimpled, while the side walls are kept
      smooth. Measurements are made at a Reynolds number of 21,000 and for Rotation
      numbers of 0 and 0.2. The measurements indicate that dimples enhance surface
      mass/heat transfer. This enhancement is stronger in the inlet passage than in the
      outlet passage. Peak mass/heat transfer occurs immediately downstream of the
      dimples, while the minimum mass/heat transfer occurs in the dimple region itself.
      Higher mass/heat transfer is also observed along the lateral edges of the dimple.
      The location of the Sherwood number peaks suggest the existence of streamwise
      vortical structures generated from the leading and lateral edges of the dimples.

PMID- 11460658
TI  - Detailed heat/mass transfer distributions in a rotating two pass coolant channel
      with engine-near cross section and smooth walls.
AB  - This paper shows results obtained by experimental and numerical investigations
      concerning flow structure and heat/mass transfer in a rotating two-pass coolant
      channel with engine-near geometry. The smooth two passes are connected by a 180
      degrees U-bend in which a 90 degrees turning vane is mounted. The influence of
      rotation number, Reynolds number and geometry is investigated. The results show a
      detailed picture of the flow field and distributions of Sherwood number ratios
      determined experimentally by the use of the naphthalene sublimation technique as
      well as Nusselt number ratios obtained from the numerical work. Especially the
      heat/mass transfer distributions in the bend and in the region after the bend
      show strong gradients, where several separation zones exist and the flow is
      forced to follow the turbine airfoil shape. Comparisons of numerical and
      experimental results show only partly good agreement.

PMID- 11460659
TI  - Analyses of heat transfer in stationary and rotating ribbed blade cooling
      passages using computational fluid dynamics.
AB  - Computational fluid dynamics (CFD) predictions of the flow patterns and heat
      transfer in simplified ribbed-wall turbine blade cooling passages were performed
      for representative stationary and rotating conditions. Analyses have been
      performed with different mesh densities and using different turbulence models to
      assess the sensitivity of predictions to these variables. Computed local heat
      transfer results are compared to measurements available in the literature to
      assess their accuracy. The results generally agree well with experiment, although
      the peak values of the heat transfer coefficients were under-predicted in the
      first leg of the channel. Some sensitivity to mesh density was seen, while the
      choice of near-wall turbulence model appeared to have little effect.

PMID- 11460660
TI  - Prediction of pressure loss and heat transfer in internal cooling passages.
AB  - This paper reports CFD-simulations of the turbulent flow, pressure loss and heat
      transfer occurring in ribbed passages. The channel section is rectangular, with
      an aspect ratio of 2.04. Ribs are square cross-section, their height is 10% of
      the channel height, and their inclination is varied from 90 degrees to 33
      degrees. Reynolds number is 30,000. Three turbulence models (k-epsilon wall
      functions and 2-layer, V2F) are used and compared to the experimental data of Cho
      et al. All three models accurately predict the pressure losses due to the ribs
      and the qualitative heat transfer distribution on the ribbed wall. However, only
      the V2F model can accurately reproduce the absolute heat transfer levels, this at
      all inclination angles. The correlation developed by Han and co-workers for
      smaller rib-heights under-predicts the friction factor and wall heat transfer
      level on the current configuration. This shows the danger of using a correlation
      outside of its application range.

PMID- 11460661
TI  - Numerical simulation of local heat transfer in rotating two-pass square channels.
AB  - 3D turbulent air flow and heat transfer developing in a two-pass square channel
      rotating in the orthogonal mode are simulated using the high-Re k-epsilon
      turbulence model and a recently developed modification of wall functions.
      Auxiliary problem for accurate definition of inlet boundary conditions formed by
      a long unheated upstream section is considered. Details of flow structure are
      presented. Local heat transfer results are compared with experimental data.

PMID- 11460662
TI  - Experimental determination of average turbulent heat transfer and friction factor
      in stator internal rib-roughened cooling channels.
AB  - In gas turbine cooling design, techniques for heat extraction from the surfaces
      exposed to the hot stream are based on the increase of the inner heat transfer
      areas and on the promotion of the turbulence of the cooling flow. This is
      currently obtained by casting periodic ribs on one or more sides of the
      serpentine passages into the core of the blade. Fluid dynamic and thermal
      behaviour of the cooling flow have been extensively investigated by means of
      experimental facilities and many papers dealing with this subject have appeared
      in the latest years. The evaluation of the average value of the heat transfer
      coefficient most of the time is inferred from local measurements obtained by
      various experimental techniques. Moreover the great majority of these studies are
      not concerned with the overall average heat transfer coefficient for the combined
      ribs and region between them, but do focus just on one of them. This paper
      presents an attempt to collect information about the average Nusselt number
      inside a straight ribbed duct. Series of measurements have been performed in
      steady state eliminating the error sources inherently connected with transient
      methods. A low speed wind tunnel, operating in steady state flow, has been built
      to simulate the actual flow condition occurring in a rectilinear blade cooling
      channel. A straight square channel with 20 transverse ribs on two sides has been
      tested for Re of about 3 x 10(4), 4.5 x 10(4) and 6 x 10(4). The ribbed wall test
      section is electrically heated and the heat removed by a stationary flow of known
      thermal and fluid dynamic characteristics.

PMID- 11460663
TI  - Contribution of heat transfer to turbine blades and vanes for high temperature
      industrial gas turbines. Part 2: Heat transfer on serpentine flow passage.
AB  - The improvement of the heat transfer coefficient of the 1st row blades in high
      temperature industrial gas turbines is one of the most important issues to ensure
      reliable performance of these components and to attain high thermal efficiency of
      the facility. This paper deals with the contribution of heat transfer to increase
      the turbine inlet temperature of such gas turbines in order to attain efficient
      and environmentally benign engines. Following the experiments described in Part
      1, a set of trials was conducted to clarify the influence of the blade's rotating
      motion on the heat transfer coefficient for internal serpentine flow passages
      with turbulence promoters. Test results are shown and discussed in this second
      part of the contribution.

PMID- 11460664
TI  - Secondary flow effect to heat transfer of a duct with discrete rib turbulators.
AB  - In the present study, three-dimensional numerical simulation is carried out for
      discrete rib arrays to investigate the local fluid and heat transfer
      characteristics. Rib pitch and gap width were varied in several steps.
      Furthermore, two kinds of rib arrays were studied, i.e. an array of ribs having
      the gaps at both spanwise ends and a staggered array of ribs with gaps at both
      spanwise ends and with gaps in the middle. Eventually, the staggered arrayed ribs
      is suggested to be best in performance of heat transfer.

PMID- 11460665
TI  - Development of non-destructive inspection method for the performance of thermal
      barrier coating.
AB  - This paper shows that our proprietary non-destructive inspection method can be
      used to effectively measure the thermal barrier performance of the thermal
      barrier coating used to coat gas turbine hot parts by the results of numerical
      analysis and laboratory experiments.

PMID- 11460666
TI  - Numerical modelling of flow and heat transfer in the rotating disc cavities of a
      turboprop engine.
AB  - A numerical analysis of the flow and heat transfer in the cavity between two co
      rotating discs with axial inlet and radial outflow of fluid, a configuration
      common in gas turbine engines, is described. The results are compared with the
      experimental data of Northrop and Owen. The effectiveness of the k-epsilon
      turbulence model with the two-layer zonal model for near-wall treatment of Chen
      and Patel is tested for this type of flow. Using three-dimensional models it is
      shown that modelling discrete holes at the outlet as opposed to a continuous
      slot, which is the approximation inherent in the two-dimensional axisymmetric
      model, has little effect on the predicted Nusselt number distribution along the
      disc surface. Results of a conjugate heat transfer analysis of a spacer in the
      turbine section of a turboprop engine are then presented.

PMID- 11460667
TI  - Verifying heat transfer analysis of high pressure cooled turbine blades and disk.
AB  - To demonstrate cooling and heat transfer technology, a core engine test was
      conducted with a turbine inlet temperature 1700 degrees C. Measurement data were
      compared with predictions for a vane, a blade, and a disk. Measured cooling
      effectiveness of the blade and the vane agreed well with predictions. CFD
      analysis was carried out for verification of the heat transfer coefficient which
      was adopted from a heat conduction analysis over the disk. The CFD model
      including bolt heads showed better results than an axisymmetric model.

PMID- 11460668
TI  - Computation of flow and heat transfer in rotating cavities with peripheral flow
      of cooling air.
AB  - Numerical solutions of the Navier-Stokes equations have been used to model the
      flow and the heat transfer that occurs in the internal cooling-air systems of gas
      turbines. Computations are performed to study the effect of gap ratio, Reynolds
      number and the mass flow rate on the flow and the heat transfer structure inside
      isothermal and heated rotating cavities with peripheral flow of cooling air.
      Computations are compared with some of the recent experimental work on flow and
      heat transfer in rotating-cavities. The agreement between the computed and the
      available experimental data is reasonably good.

PMID- 11460669
TI  - Turbulence modeling in simulation of gas-turbine flow and heat transfer.
AB  - The popular k-epsilon type two-equation turbulence models, which are calibrated
      by experimental data from simple shear flows, are analyzed for their ability to
      predict flows involving shear and an extra strain--flow with shear and rotation
      and flow with shear and streamline curvature. The analysis is based on
      comparisons between model predictions and those from measurements and large-eddy
      simulations of homogenous flows involving shear and an extra strain, either from
      rotation or from streamline curvature. Parameters are identified, which show the
      conditions under which performance of k-epsilon type models can be expected to be
      poor.

PMID- 11460670
TI  - A review of turbine blade tip heat transfer.
AB  - This paper presents a review of the publicly available knowledge base concerning
      turbine blade tip heat transfer, from the early fundamental research which laid
      the foundations of our knowledge, to current experimental and numerical studies
      utilizing engine-scaled blade cascades and turbine rigs. Focus is placed on high
      pressure, high-temperature axial-turbine blade tips, which are prevalent in the
      majority of today's aircraft engines and power generating turbines. The state of
      our current understanding of turbine blade tip heat transfer is in the
      transitional phase between fundamentals supported by engine-based experience, and
      the ability to a priori correctly predict and efficiently design blade tips for
      engine service.

PMID- 11460671
TI  - Unsteady flow modelling in turbine stage.
AB  - The paper deals with the problems of unsteady flow modelling in turbine stage.
      The impact of unsteadiness in the design procedure as well as in the real flow
      phenomena are briefly addressed. After a discussion of the physical aspects of
      the real flow in turbine stage which differ from the unsteady flow in a single
      row environment, the paper reports a survey of the actual and more recent
      approaches to the numerical modelling on the unsteady flow in multiple rows
      environment. The classical steady models, used for long time in the design
      procedure, are addressed and their limits are focused. The more complex
      procedures ranging from quasi-unsteady methods to the fully unsteady methods are
      reported and investigated in details. The discussion on the specific features of
      the different approaches is pointed to assess the accuracy, the feasibility, the
      robustness and the usability (i.e. the computer time and storage requirements).
      Sample results from the author research activity are reported and presented.
      Discussion of crucial and open questions to improve the prediction capability of
      the methods are finally reported as well as some comments on the possibility to
      joint classical (steady methods) and advanced approaches (fully unsteady methods)
      to improve the actual design procedure are addressed.

PMID- 11460672
TI  - The detailed structure and behavior of discrete cooling jets in a turbine.
AB  - Three-dimensional jets are an efficient way of cooling the walls of modern high
      pressure turbines. Introduced in the external flow that develops around the
      turbine blade, they are associated with a set of vortex structures. The purpose
      of this paper is to underline the respective origin and importance of these
      structures, with reference to both experimental and numerical results. Steady and
      unsteady vortices will be analyzed. Recommendations for numerical simulations
      will be proposed from these observations.

PMID- 11460673
TI  - The cytochrome P450 1A gene (CYP1A) from European flounder (Platichthys flesus),
      analysis of regulatory regions and development of a dual luciferase reporter gene
      system.
AB  - Concensus primers designed to CYP1A-conserved regions were used to amplify a 1.3
      kb probe from flounder genomic DNA via polymerase chain reaction (PCR). A 14-kb
      clone was isolated from a flounder genomic library constructed in lambda FIXII.
      Of this clone, 8 kb was sequenced, including 3 kb of upstream sequence. The
      predicted amino acid sequence showed closest similarity to plaice CYP1A1 (98%).
      Gene structure conformed to the seven exons and six introns common to previous
      CYP1A sequences, but intron lengths were not conserved. Concensus sequences
      corresponding to xenobiotic and other response elements as well as TATA, CAAT and
      GC boxes were identified. Upstream sequence (3.5 kb) including the first exon and
      intron up to the putative start codon were amplified via PCR and inserted
      upstream of the luciferase gene in a pGL3 reporter gene construct. The HepG2
      mammalian hepatoma cell line was transiently co-transfected with the flounder
      CYP1A reporter gene construct and the pRL-CMV internal control construct. The
      maximal induction upon exposure to 100 nM 3-MC was 4.4-fold in comparison with
      carrier-treated cells. Use of deletion constructs resulted in loss of
      inducibility.

PMID- 11460674
TI  - Mysids and trace metals: disruption of swimming as a behavioural indicator of
      environmental contamination.
AB  - Mysids are used frequently in standard laboratory studies of acute exposure to
      chemical contaminants. Their value for sub-lethal measures of biological response
      to predict the potential effects of environmental toxicants, however, has yet to
      be determined. In estuaries, mysids maintain their optimum position independent
      of the forces of river flow and tides; therefore, any disruption of swimming
      behaviour will have significant implications for their survival and position
      maintenance. In the present study, the effects of cadmium on the swimming
      behaviour of the hyperbenthic estuarine mysid Neomysis integer, which occupies
      the heads of European estuaries, are presented. Following 7 day exposure to
      cadmium, swimming behaviour (ability and orientation) was disrupted at 0.5
      microgram Cd(aq)2+ l-1, a significantly lower cadmium concentration than that
      causing mortality (7 day LC50 of 2.58 micrograms Cd(aq)2+ l-1). The results of
      this investigation highlight the advantages of behavioural toxicity tests for
      predicting the influence of pollutants and support the use of mysids for
      estuarine monitoring.

PMID- 11460675
TI  - Sulfation and glucuronidation of benzo[a]pyrene-7,8-dihydrodiol in intestinal
      mucosa of channel catfish (Ictalurus punctatus).
AB  - Intestinal metabolism plays a significant role in the bioavailability of ingested
      environmental toxicants. In this study, the potential for first pass, phase 2
      biotransformation of benzo[a]pyrene-7,8-dihydrodiol (BaP-7,8-diol) in intestinal
      mucosa was examined. Sulfotransferase and Uridine 5'-Diphospho-Glucuronyl
      transferase activity were measured in cytosol, and microsomes respectively.
      Radiolabeled conjugation products were analyzed by TLC and high-performance
      liquid chromatography (HPLC). The results indicated that BaP-7,8-diol was a poor
      substrate for intestinal sulfotransferase. Vmax for the sulfation of BaP-7,8-diol
      was 0.002 nmol mg-1 min-1, which is at least three orders of magnitudes lower
      than the Vmax for phenolic BaP metabolites. Studies with 3'phosphoadenosine-5'
      phosphosulfate (PAP)-35S as co-substrate showed that an unidentified compound in
      the reaction mixture was sulfated, dependent on the BaP-7,8-diol concentration.
      This could indicate that BaP-7,8-diol was interacting with a regulatory site on
      the enzyme and stimulated sulfation of an endogenous molecule in cytosol. Kinetic
      analysis of microsomal glucuronidation resulted in a Vmax of 0.30 nmol mg-1 min-1
      (+/- 0.06 S.D., n = 4), with a Km of 23.39 microM (+/- 2.66 S.D.). The Km for the
      co-substrate UDP-glucuronic acid was approximately 43 microM. The slow rates for
      sulfation and glucuronidation of BaP-7,8-diol may explain its relatively high
      systemic availability when ingested or produced by intestinal phase 1 enzymes.

PMID- 11460676
TI  - Interactions of chlorpyrifos and methyl mercury: a mechanistic approach to assess
      chemical mixtures.
AB  - The mechanism of interaction between chlorpyrifos, an organophosphate
      insecticide, and methyl mercury was assessed utilizing the amphipod, Hyalella
      azteca. Previous studies have demonstrated that chlorpyrifos and methyl mercury
      interact additively with survival as the endpoint. In addition, exposure to
      chlorpyrifos and methyl mercury increased the accumulation and decreased the
      elimination of methyl mercury. To further examine the mechanism responsible for
      these interactions, the in vivo and in vitro inhibition of acetylcholinesterase
      enzyme activity was assessed following exposure to methyl mercury and
      chlorpyrifos. In vivo, methyl mercury antagonized the effects of chlorpyrifos on
      acetylcholinesterase inhibition. Additional studies demonstrated that methyl
      mercury did not affect the in vitro bioactivation of chlorpyrifos or the
      subsequent inhibition of acetylcholinesterase enzyme activity. Chemical-chemical
      interactions were examined utilizing chromatographic techniques and suggested the
      formation of a chlorpyrifos-methyl mercury complex. The formation of this complex
      may result in increased accumulation of methyl mercury, apparent additive
      toxicity, and protection against chlorpyrifos-mediated acetylcholinesterase
      inhibition.

PMID- 11460677
TI  - Lead and Aroclor 1254 disrupt reproductive neuroendocrine function in Atlantic
      croaker.
AB  - We have previously shown that lead (lead chloride) and a polychlorinated biphenyl
      (PCB) mixture (Aroclor 1254) can alter hypothalamic serotonin (5
      hydroxytryptamine, 5-HT) content, and pituitary gonadotropin II (GTH II) release
      in vitro, in the Atlantic croaker (Micropogonias undulatus). In the present study
      we investigated whether impairment of the hypothalamic 5-HT pathway involves
      alterations in tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT
      biosynthesis, or monoamine oxidase (MAO), the catabolic enzyme. Aroclor 1254 (1
      mg/kg body wt. for 30 days) significantly inhibited hypothalamic TPH activity
      without altering MAO activity, and caused a significant decline in 5-HT content.
      On the other hand, lead exposure (15 mg/kg body wt. for 30 days) only induced a
      slight decrease in hypothalamic 5-HT content and TPH activity, and a minor
      increase in MAO activity. However, both Aroclor 1254 and lead significantly
      inhibited the GTH II response to stimulation by a luteinizing hormone-releasing
      hormone analog (LHRHa) in vivo and caused reduced gonadal growth. These results
      demonstrate that impairment of hypothalamic serotonin metabolism by Aroclor 1254
      involves inhibition of 5-HT synthesis, whereas lead does not exert a profound
      influence on 5-HT metabolism. The decline in 5-HT availability due to reduced 5
      HT synthesis in the PCB-exposed fish may result in disruption of the stimulatory
      5-HT-GnRH pathway controlling GTH II secretion leading to impairment of gonadal
      growth.

PMID- 11460678
TI  - Chemical interference with genomic and nongenomic actions of steroids in fishes:
      role of receptor binding.
AB  - The characteristics of steroid nuclear and membrane receptors and their
      interactions with xenobiotic chemicals in two marine perciform species, Atlantic
      croaker (Micropogonias undulatus) and spotted seatrout (Cynoscion nebulosus) are
      briefly reviewed. Several organochlorines that bind to the nuclear progesterone
      receptor in mammals show negligible binding to the nuclear progestogen receptor
      in seatrout ovaries. Two distinct nuclear androgen receptors with different
      tissue distributions have been identified in croaker, but only one of them binds
      xenobiotic anti-androgens previously identified in mammals. Multiple forms of the
      nuclear estrogen receptor (ER) have been identified in fishes. The ER in croaker
      testis has a higher affinity than the croaker liver ER for estrogens and
      xenoestrogens and may be more susceptible to chemical interference. In addition,
      differences in the feedback effects of estrogens and xenoestrogens on
      gonadotropin secretion in croaker are observed, depending on the stage of the
      reproductive cycle. Finally, the first clear evidence in any vertebrate for
      xenobiotic chemical interference with the nongenomic actions of steroids by
      binding to steroid membrane receptors was obtained with the seatrout ovarian
      progestogen membrane receptor and since has been confirmed with progestogen and
      estrogen membrane receptors in croaker sperm and testes. These various factors
      that influence chemical/steroid receptor interactions are likely to significantly
      modify steroid hormone actions at target tissues and consequently the
      toxicological effects of chemical exposure.

PMID- 11460679
TI  - Exposure to environmentally relevant concentrations of different nonylphenol
      formulations in Japanese medaka.
AB  - The time course of exposure to p-nonylphenol (NP) from two different sources was
      compared to equivalent exposures of 17-beta-estradiol (E2) and a solvent control
      (ethanol; EtOH). Japanese medaka were exposed for 4 days to a nominal
      concentration of 20 micrograms/l of either NP-I (Schenectady International,
      Inc.), NP-II (Aldrich), or E2, and were then placed in untreated water for 5
      days. Tissue samples were taken at two time points during the 4-day exposure and
      two time points during the 5 days following exposure. Liver homogenates were
      analyzed using a western blot to detect vitellogenin (VTG) and quantified by
      measuring the optical density for each lane. Preliminary results indicate that E2
      significantly increased VTG staining above the level observed in EtOH-treated
      controls for both males and females. A two-way analysis of variance (ANOVA)
      indicates that NP from both sources, as well as E2, significantly increased VTG
      staining in males (ANOVA, n = 48, P < 0.001; Tukey pairwise tests, all P <
      0.008). A significant increase in VTG was observed in E2-treated males and
      females the first day following transfer into toxicant-free water (two-way
      ANOVAs, both n = 48, P < 0.003; Tukey pairwise tests, all P < 0.019). If
      confirmed, this extended response observed for low-level exposures may represent
      a significant factor for sampling scenarios following pulsitile exposure.

PMID- 11460680
TI  - Metabolism and organ distribution of nonylphenol in Atlantic salmon (Salmo
      salar).
AB  - Nonylphenol (NP) is a breakdown product of alkylphenol polyethoxylates (APEs), an
      important class of non-ionic surfactants that are widely used in many detergent
      formulations and plastic products for industrial and domestic use. A complex
      microbial degradation pattern, characterized by the formation of several
      metabolic products that are more toxic than the parent compound, has been
      established for APEs. We have studied the in vivo metabolism and organ
      distribution of NP in juvenile salmon. Fish were exposed to a single oral dose of
      [3H]-4-n-NP (1295 KBq, 25 micrograms) and sampled at 24, 48 and 72 h after
      exposure. Metabolites were separated by radio-high-performance liquid
      chromatography and tentatively identified by cochromatography with standards
      characterized by mass spectrometry. Our results show that 4-n-NP was mainly
      metabolized in vivo to its corresponding glucuronide conjugate and to a lesser
      extent to various hydroxylated and oxidated compounds. Biliary excretion at 72 h
      after dosing amounted to 2.83 +/- 0.75% of the administered radioactivity.
      Kinetic analysis shows that NP-glucuronide accounted for 83, 95 and 81% of total
      radioactivity in the HPLC-injected bile sample at 24, 48 and 72 h, respectively,
      after exposure. The half-life of residues in carcass and muscle was between 24
      and 48 h after exposure.

PMID- 11460681
TI  - Lack of effect of beta-naphthoflavone on induction of Nramp genes in adult
      rainbow trout Oncorhynchus mykiss.
AB  - Natural resistance-associated macrophage protein (Nramp) genes in rainbow trout,
      Oncorhynchus mykiss, were identified and characterized. The greatest mRNA level
      encoding these genes was in the developing ovary of rainbow trout. We evaluated
      the response of these genes to a certain aromatic hydrocarbon receptor (AHR)
      agonist. Adult rainbow trout were treated with beta-naphthoflavone (BNF) (50 and
      100 mg/kg) for 48 h. Using reverse-transcriptase polymerase chain reaction with
      ovary and head kidney RNA and specific alpha and beta Nramp primers, a 400 bp
      Nramp-alpha- and a 400 bp Nramp-beta-specific cDNA were obtained. There were no
      changes in the alpha and beta Nramp mRNA levels in the ovary following BNF
      administration. CYP1A1 mRNA was increased in the ovary and kidney, suggesting the
      presence of AHR in rainbow trout ovary, while the AHR agonist produced no effect
      on Nramp mRNAs.

PMID- 11460682
TI  - Developmental evaluation of a potential non-steroidal estrogen: triclosan.
AB  - Triclosan is an antibacterial agent commonly used in industry and often detected
      in waste-water effluent. The potential of triclosan to act as an endocrine
      disruptor was examined because its chemical structure closely resembles known non
      steroidal estrogens (e.g. DES, bisphenol A). Japanese medaka fry (Oryzias
      latipes) were exposed for 14 days beginning 2 days post-hatch to triclosan (100,
      10, 1 micrograms/l), 17-beta estradiol (E2; 1 microgram/l), or a solvent control
      (ethanol). Two months post-exposure, the phenotypic sex of each adult was
      assessed visually using sexually dimorphic fin shape and size. The proportion of
      females in each group was similar for triclosan-exposed animals and solvent
      treated controls (ethanol 53%, 1 ppb 58%, 10 ppb 45%, 100 ppb 36%) although E2
      treatment did produce 92% female adults. Sexually dimorphic fin traits were
      quantified to look for potential effects of triclosan and E2 on the development
      of secondary sexual characters. These results do not support the hypothesis that
      triclosan is potently estrogenic. However, changes in fin length and non
      significant trends in sex ratio suggest triclosan is potentially weakly
      androgenic.

PMID- 11460683
TI  - Modulation of trout 7-ethoxyresorufin-O-deethylase (EROD) activity by estradiol
      and octylphenol.
AB  - Estrogens appear to have a modulating effect on the expression of cytochrome
      P4501A (CYP1A) in fish. A number of in vivo studies have demonstrated that
      hepatic CYP1A expression in females decrease during sexual maturation when plasma
      levels of 17 beta-estradiol (E2) increase, or in cases when the fish in injected
      with E2. Since a number of environmental contaminants have weak estrogen-like
      activities, the question arises if these compounds are able to modulate CYP1A
      expression as well. In the present study, we used in vitro monolayer cultures of
      rainbow trout, Oncorhynchus mykiss, liver cells to compare concentration
      dependent (10(-9) to 10(-5) M) effects of the natural steroid E2 and the non
      steroidal xenoestrogen 4-tert-octylphenol (OP) on CYP1A-catalyzed 7
      ethoxyresorufin-O-deethylase (EROD) activity. The concentration dependency of the
      estrogenic activity of the two test compounds was assessed by determination of
      hepatocellular vitellogenin (Vg) release into the culture medium. Exposure of
      hepatocytes to E2 concentrations of 10(-8) M and higher led to a significant
      inhibition of basal cellular EROD activity. On the contrary, exposure to OP did
      not result in an inhibition of EROD activity, even at OP concentrations (10(-6)
      M, 10(-5) M) which were associated with a significant induction of Vg synthesis.

PMID- 11460684
TI  - Immune function, hepatic CYP1A, and reproductive biomarker responses in the gulf
      killifish, Fundulus grandis, during dietary exposures to endocrine disrupters.
AB  - The gulf killifish, Fundulus grandis, was used to determine the influence of
      biological rhythms on three biomarker responses. We first developed monoclonal
      antibodies against the model's immunoglobulins and vitellogenin in order to
      measure antibody responses and vitellogenesis, respectively. We then treated
      adults with 10, 1, 1, and 10 ppm of Aroclor 1254, tribuyltin, 3
      methylcholanthrene, and nonyl-phenol, respectively, in mixtures over a 16-week
      period. The study followed Vibrio anguillarum-specific antibody responses,
      hepatic CYP1A, and plasma vitellogenin levels in the morning and again in the
      evening at 2-week intervals. The contaminated diet suppressed secondary antibody
      responses, but only in the morning. The contaminated diet also altered CYP1A, but
      not vitellogenesis. In addition, fish in the control group exhibited daily and
      seasonal differences in specific antibody levels and CYP1A induction. Moreover,
      circulating vitellogenin levels in control males sampled in the morning increased
      throughout the exposure, but remained below those of females. This study
      underscores the need to consider normal physiological rhythms when employing
      biomarkers in toxicology.

PMID- 11460685
TI  - Concentration-dependent effects of nonylphenol on testis structure in adult
      platyfish Xiphophorus maculatus.
AB  - Nonylphenol has been found to exert estrogenic effects in fish and may affect the
      fertility of male fish. The objective of this study was to use the platyfish,
      Xiphophorus maculatus, as a model to evaluate the concentration-dependent effects
      of nonylphenol on the testicular structure. A tendency of a concentration
      dependent decrease in the gonadosomatic index was observed after 28 days of
      treatment with nonylphenol. Histological examination revealed marked effects of
      nonylphenol on the testis structure. The effects were more pronounced at the
      higher concentrations of nonylphenol. This study strongly suggests that exposure
      to nonylphenol can result in decreased fertility in X. maculatus males.

PMID- 11460686
TI  - Conservation of a glutathione S-transferase in marine and freshwater fish.
AB  - We have previously reported the isolation and cloning of glutathione S
      transferase (GST) cDNAs from two marine fish, English sole (Pleuronectes vetulus)
      and starry flounder (Platichthys stellatus), that exhibited > 95% identity to
      plaice (Pleuronectes platessa) GST-A Aquatic Toxicol., 44, 171-182]. In the
      present study, we have used reverse transcription-polymerase chain reaction (RT
      PCR) analysis to isolate a 471 nucleotide GST-like cDNA from largemouth bass
      (Micropterus salmoides) liver. Sequence identity of the largemouth bass partial
      cDNA to plaice GST-A was approximately 90%. Northern blotting analysis using the
      partial GST cDNA from English sole as a probe detected a single band of
      approximately 1 kb in English sole liver and a slightly larger GST-like band that
      was highly expressed in largemouth bass liver. In addition, a faint band of
      similar size was recognized in brown bullhead (Ameriurus nebulosus) liver, but
      not in channel catfish (Ictalurus punctatus) liver. In conclusion, we have
      extended our studies of GST expression in flatfish and have isolated an
      additional GST-A-like cDNA from a largemouth bass. Conservation of a GST-A like
      cDNA among certain marine flatfish and freshwater species suggests an important
      function for this gene.

PMID- 11460687
TI  - Estrogenic and CYP1A response of mummichogs and sunshine bass to sewage effluent.
AB  - Recent studies demonstrating feminization of effluent-exposed wild-caught male
      fish in the UK have prompted much research regarding the estrogenic activity of
      effluent from municipal sewage treatment plants (MSTPs). To investigate the
      estrogenicity and cytochrome P450 1A (CYP1A) induction potency of MSTP effluent,
      two species of fish, adult male mummichogs, Fundulus heteroclitus, and juvenile
      sunshine bass, Morone saxatilis x Morone chrysops, were exposed to un-chlorinated
      effluent (75% effluent, 25% seawater) from a large MSTP in Yonkers, NY, USA.
      After a 21-day static-daily (75%) renewal exposure, significant elevations over
      controls were observed in levels of vitellogenin (VtG) in plasma (1730%) and
      liver (131%) in effluent-exposed sunshine bass. In contrast, hepatic VtG was not
      elevated in mummichogs; plasma VtG was not measured in this species. Effluent
      exposure elevated hepatic CYP1A protein (140-145%) and ethoxyresorufin-O
      deethylase (EROD) activity (408-598%) in both species. These findings suggest
      ontogenetic and/or species differences in response to estrogenic compounds in
      MSTP effluent. Furthermore, the elevation of CYP1A in response to sewage effluent
      exposure indicates the presence of additional compounds that may alter xenobiotic
      and/or steroid biotransformation in fish.

PMID- 11460688
TI  - Effects of methyl testosterone exposure on sexual differentiation in medaka,
      Oryzias latipes.
AB  - Studies were conducted to characterize effects of a known androgen on sexual
      differentiation and development of medaka, Oryzias latipes (d-rR strain), at two
      life stages. Embryos were injected with graded doses of methyl testosterone (MT)
      prior to epiboly. The occurrence of sex-reversal, and the gonadosomatic index
      (GSI) were evaluated in adults. Primary germ cells were counted and gonad volumes
      calculated for larvae to determine if sex-reversal could be detected at an early
      life stage. Sex-reversal of genetic females to phenotypic males was observed at
      both life stages. The GSI for phenotypic females was greater than for phenotypic
      males, while the GSI in XX males was similar to XY males. MT appeared to reduce
      the GSI of XX females exposed to MT but not sex-reversed. Our results indicate
      that embryonic exposure to androgens influences sexual development in medaka.
      Utilizing the d-rR strain of medaka allows detection of an effect as early as 2
      weeks after chemical exposure making this a useful tool to screen chemicals for
      effects on sexual differentiation.

PMID- 11460689
TI  - Comparative vitellogenic responses in three teleost species: extrapolation to in
      situ field studies.
AB  - Induction of vitellogenin (VTG) was compared among three teleostean species to
      determine their relative sensitivity of exposure to 17 beta-estradiol (E2).
      Japanese medaka (Oryzias latipes), sunshine bass (Morone saxatalis x Morone
      chrysops) and channel catfish (Ictalurus punctatus) were exposed to aqueous
      concentrations of E2 ranging from 10 to 100,000 ng/l for 21 days. Respective EC50
      values for plasma VTG detected by western blot in medaka, catfish and bass were
      200, 170 and 1560 ng E2/l. Since these EC50 values are based on VTG induction
      curves calculated relative to control values, they indicate differences in
      species' sensitivity to E2 exposure. Catfish and bass VTG responses obtained in
      laboratory exposures were compared to VTG responses previously observed with 21
      day wastewater treatment plant effluent exposures. Plasma VTG induction in
      effluent-exposed fish ranged from 14 to 82% above reference values depending on
      species. Extrapolation of field responses with laboratory-exposed fish indicate
      catfish and bass were exposed to the equivalent of 27-240 ng E2/l in sewage
      effluent.

PMID- 11460690
TI  - Determining the sensitive developmental stages of intersex induction in medaka
      (Oryzias latipes) exposed to 17 beta-estradiol or testosterone.
AB  - Certain environmentally persistent compounds can adversely affect reproduction by
      acting as steroid hormone agonists or antagonists. The goal of the present study
      was to determine the developmental stage most susceptible to exogenous hormone
      (estradiol and testosterone) exposure using a small teleost model. In the first
      (pilot study) of two experiments, medaka (Oryzias latipes), at varying
      developmental stages, were bath-exposed to 5 micrograms/l 17 beta-estradiol for
      24 h. At 5 months of age, fecundity, fertility and embryo and larval viability
      (reproductive success) were investigated in control and exposed groups. Fish at
      1, 1.5, 2 and 5.5 months of age were also sampled, processed and examined
      histologically for gonadal alteration. No significant differences in mortality,
      gonadal morphology, body weight, sex-ratio or time to maturity were seen between
      control and exposed fish. At 5 months, however, when exposure groups were
      compared to controls, significant differences were seen in reproductive success
      and viability of offspring. A second experiment exposed embryo stage 10, and 1-,
      7- and 21-day-old larvae for 6 days to 15 micrograms/l 17 beta-estradiol or 100
      micrograms/l testosterone. No significant differences were seen at 5 months in
      mortality, body weight, or time to sexual maturity. However, sex-ratios were
      significantly biased toward female in the stage 10, 1- and 7-day post-hatch
      estradiol exposure groups. No significant changes in sex-ratio were associated
      with testosterone exposure at any developmental stage. Further, intersex gonads
      were observed in fish from all groups exposed to 15 micrograms/l estradiol. Only
      those fish exposed as newly hatched fry or at 1 week post-hatch displayed
      intersex gonads following 100 micrograms/l testosterone exposure. Data from these
      experiments show that newly hatched fry are that life stage most sensitive to
      hormone exposure and the most appropriate to use in determining effects of known
      endocrine-disrupting compounds.

PMID- 11460691
TI  - The effects of glutathione depletion on reproductive success in oysters,
      Crassostrea virginica.
AB  - Glutathione (GSH) is a ubiquitous tripeptide that functions as a very important
      modulator of cellular homeostasis, including detoxification of metals and
      oxyradicals. Therefore, depletion of GSH may predispose organisms to pollutant
      stress. Reproductively active oysters (Crassostrea virginica) were exposed to
      buthionine sulfoximine in the laboratory to deplete gonadal GSH. The effects of
      metal exposures (Cd and Cu) on fertilization and developmental assays were
      evaluated using gametes from control and GSH-depleted adults. Fertilization
      success was not affected by GSH status, i.e. the fertilization rates of gametes
      derived from GSH-depleted adults were the same or slightly higher. However, GSH
      depletion did increase the susceptibility of developing embryos to metal
      toxicity, i.e. adverse effects on embryonic development were observed at lower
      metal concentrations with gametes derived from GSH-depleted adults. These effects
      may be related to diminished removal of free radicals or increased availability
      of metals. Whereas sperm penetration of embryonic membranes and fertilization
      success may be facilitated by free radicals, the persistence of free radicals
      during subsequent developmental periods may adversely affect differentiation and
      normal development. GSH probably also plays an important role in scavenging toxic
      metals and reducing metal interactions with essential developmental processes.
      These results suggest that parental depletion of GSH may increase the
      susceptibility of embryos to metal toxicity.

PMID- 11460692
TI  - gamma-Glutamyl transpeptidase as a possible marker of Sertoli cells in fish
      testes for studies of xenoestrogens.
AB  - Estrogenic chemicals are known to have marked effects on the reproductive system
      of male fish. Finding useful markers of reproductive effects are therefore of
      great importance and interest. gamma-Glutamyl transpeptidase (gamma-GTP) is a
      possible marker of Sertoli cells in testes of fish. In the present study we have
      examined the relationship between the activity of gamma-GTP and the histological
      structure of the Sertoli cells in testes of five fish species (guppy, Poecilia
      reticulata; platyfish, Xiphophorus maculatus; eelpout, Zoarces viviparus; rainbow
      trout, Oncorhynchus mykiss; flounder, Platichthys flesus). In general we found
      that the more distinct the Sertoli cells the higher the activity of gamma-GTP.

PMID- 11460693
TI  - PCB uptake and accumulation by oysters (Crassostrea virginica) exposed via a
      contaminated algal diet.
AB  - Reproductively active oysters were fed daily with 0.2 g algal paste containing 0,
      0.1, and 1.0 microgram polychlorinated biphenyls (PCBs) (1:1:1 mixture of Aroclor
      1242, 1254 and 1260) for either 15 or 30 days, and accumulation of PCBs in
      different organ tissues and eggs assessed. The effects of PCB exposure on lipid
      content, lipid class and fatty acid composition were also evaluated. PCBs were
      accumulated by the oysters and transferred to the eggs. PCB accumulation in
      oysters was dose, time and tissue dependent. Mean PCB contents were 3150, 1970,
      and 250 ng/g dry wt., respectively, in the visceral mass, gills + mantle and
      muscle of oysters fed algal paste containing 1.0 microgram PCBs for 30 days. The
      PCBs in the eggs from the same oysters reached 671 ng PCBs/g dry wt. Feeding
      oysters with PCB-sorbed algal paste for 30 days significantly increased
      phospholipid and free fatty acid contents in gills + mantle tissue compared to
      the same tissues in the undosed control.

PMID- 11460694
TI  - Ovo-testis and disturbed reproductive cycle in the giant abalone, Haliotis
      madaka: possible linkage with organotin contamination in a site of population
      decline.
AB  - Histological examination of gonads as well as chemical analysis of organotin
      compounds in tissues of the giant abalone, Haliotis madaka, was conducted to
      evaluate possible endocrine disruption and to consider the causal factors for the
      decline of abalone stocks in Japan. Abalone specimens were collected from two
      different areas, Tsushima as a reference site and Jogashima as a site
      representative of declining abalone populations, each month from September 1995
      to November 1996. Scores were given to the development stages of reproductive
      cells in the ovary and testis. The degree of sexual maturation was evaluated by
      calculating the mean value of a histogram of these scores for the reproductive
      cells of each abalone. The temporal variations in degree of sexual maturation
      showed that female and male abalone from Tsushima matured synchronously, while
      those from Jogashima did not. The observed maximum reproductive developmental
      score in abalone from Jogashima was much lower than that from Tsushima, because
      immature females were present at the former site throughout the spawing season.
      Approximately 20% of the abalone from Jogashima were masculinized females with an
      ovo-testis. The masculinization of female abalone was similar to the imposex,
      typically induced in other gastropod molluscs by tributyltin (TBT) and
      triphenyltin (TPhT) from antifouling paints. Concentrations of TBT and TPhT in
      the muscles of abalone from Jogashima (n = 83) of 4.9 +/- 4.4 ng/g wet wt and 6.3
      +/- 6.6 ng/g wet wt, respectively, were significantly higher than those from
      Tsushima (n = 125) (P < 0.01) of 0.8 +/- 0.8 ng/g wet wt and 0.6 +/- 1.3 ng/g wet
      wt, respectively. In situ exposure of abalone from Tsushima caged near a dockyard
      in Jogashima for 7 months (from the immature to the mature stage) resulted in
      spermatogenesis in the ovary of approximately 90% of females. Endocrine
      disruption may be caused in the giant abalone by organotin compounds from
      antifouling paints, which are possibly one of the causal factors for the decline
      of Japanese abalone stocks.

PMID- 11460695
TI  - Distribution of microsomal CO-binding chromophores and EROD activity in sea
      anemone tissues.
AB  - Our previous studies indicated that sea anemone microsomes contain cytochrome
      P450 (CYP) and have ethoxyresorufin O-dealkylation (EROD) activity. Other marine
      invertebrates have discrete organs which concentrate cytochromes P450, whereas
      cnidarians have evolved only to the tissue level of development. To examine the
      distribution of CYP in sea anemones, microsomes were prepared from the following
      tissue regions of two sea anemones, Anthopleura xanthogrammica: outer (heavy
      muscular wall), inner (imperfect and perfect mesentery, and retractor muscle),
      soft (digestive sac, gonads, and mesentery filaments), and tentacular (including
      algal/diatom symbiont). The cytochrome P450 content was distributed relatively
      evenly among the tissue regions. In contrast, the 418-nm CO-binding chromophore
      was approximately 10 times greater in the outer region than in any other region.
      Further, the 490-nm peak (which interferes with quantification of CYP in sea
      anemones) was greater in the outer region. In general, the EROD activity was
      comparable in the inner and soft regions and highest in the tentacles. However,
      the EROD results may have been complicated by the presence of the algal/diatom
      symbiont.

PMID- 11460696
TI  - Embryotoxicity of butyltin compounds to the sea urchin Paracentrotus lividus.
AB  - Tributyltin (TBT) has been widely employed in marine anti-fouling paints as a
      biocide, although it represents a serious risk, particularly in estuarine and
      coastal water/sediment ecosystems. In this study, the embryotoxic effects of TBT
      and its degradation products, dibutyltin (DBT) and monobutyltin (MBT), were
      analyzed during the development of the sea urchin Paracentrotus lividus from post
      fertilization to the pluteus stage, to better clarify ecotoxicological impact.
      The embryotoxicity of butyltins is concentration-dependent and increases
      proportionally with number of butyl groups. Significant growth reduction was
      observed at TBT concentrations as low as 0.01 microgram l-1; 1 microgram l-1 was
      the maximum concentration allowing embryos to reach the pluteus stage at 48 h
      post-fertilization. Development was blocked at the morula or blastula stage with
      higher TBT concentrations. DBT and MBT are less toxic: slowed development and a
      decrease in pluteus size occurred at 10 micrograms l-1 DBT and 0.5 mg l-1 MBT.
      Effects on both skeletal deposition and blocked embryonic development are
      suggested to be due to the interference of organotin compounds with intracellular
      calcium homeostasis.

PMID- 11460697
TI  - The impact of musk ketone on reproduction in zebrafish (Danio rerio).
AB  - Nitro musks are a group of nitrated benzenes mainly used by the fragrance
      industry as a substitute for natural musk. Two of the most common nitro musks,
      musk xylene and musk ketone, have been detected in water, fish, human adipose
      tissue, as well as in human breast milk. In this study, female zebrafish were
      dietary-exposed to musk ketone, prior to spawning with unexposed males. The fish
      were exposed for 8 weeks at two different dose levels. Accumulation of the
      compound in the fish as well as reproductive success were studied. Exposed
      females had reduced body weight and length, as well as reduced liver- and gonad
      somatic index. The results from the reproduction study showed a dose-dependent
      reduction in fecundity. Early life-stage mortality was increased and the median
      survival time was reduced. In addition, an embryo/larvae toxicity test was
      performed, using newly fertilized zebrafish eggs from unexposed parental fish.
      Eggs were exposed to a series of different concentrations of musk ketone via the
      surrounding water. A NOEC value of 10 micrograms/l and a LOEC value of 33
      micrograms/l was determined. Conclusively, the present study clearly shows that
      musk ketone negatively affects reproduction and early life-stage survival in
      zebrafish.

PMID- 11460698
TI  - Intersexes in Mississippi River shovelnose sturgeon sampled below Saint Louis,
      Missouri, USA.
AB  - The Missouri Department of Conservation detected high organochlorine levels in
      tissues of fish from the Mississippi River south of Saint Louis. Chlordane, which
      is both a carcinogen and an endocrine disrupter, reached 2960 micrograms/kg in
      fillets of shovelnose sturgeon, Scaphirhynchus platyorynchus, and 1926
      micrograms/kg in their roe, wet weight basis. Polychlorinated biphenyls (PCBs)
      and p,p'-dichlorodiphenyldichloroethylene (DDE) in roe have reached 5810 and 780
      micrograms/kg, respectively. The purpose of this study was to determine if
      endocrine disrupters and carcinogens are a potential cause of the significantly
      diminished reproduction capacity and population declines in the endangered pallid
      sturgeon, Scaphirhynchus albus. Twenty-four surrogate shovelnose sturgeons were
      sampled north of Saint Louis where contaminant levels were lower compared with 17
      sampled south of Saint Louis where contaminant levels were high. Liver and gonad
      tissues were formalin-fixed, histologically processed and examined. Neoplasms
      were not found. The principal finding was that the testes of two of the seven
      downstream male fish contained ovigerous lamellae, in addition to mature sperm.
      Since sturgeons are gonochoristic and intersexes are rare and unusual, the
      occurrence of intersex in 29% of the male Mississippi River shovelnose sturgeon
      examined from a population contaminated with chlordane and other chemicals raise
      concern for human health, species biodiversity and preservation of waterway
      quality. These findings, however, need to be corroborated by expanded studies
      with a higher sample size.

PMID- 11460699
TI  - Analysis of mutations in the p53 tumor suppressor gene and Ki- and Ha-ras proto
      oncogenes in hepatic tumors of European flounder (Platichthys flesus).
AB  - DNA from five tumors, three other-injured livers and two normal liver tissue
      samples from the European flounder were analyzed for mutations in exons 5-8 of
      the tumor suppressor gene p53 and at codons 12, 13 and 61 of Ha- and Ki-ras proto
      oncogenes. No tumor-specific mutations were identified by direct sequencing and
      single-strand conformation polymorphism of these genes. A number of silent
      polymorphisms were noted in p53. In addition to a need for more extensive
      analyses of flounder liver tumor samples for ras or p53 mutations, other cancer
      related genes should be investigated.

PMID- 11460700
TI  - In vivo and in vitro effects of benzothiazole on sheepshead minnow (Cyprinodon
      variegatus).
AB  - Benzothiazole, a common chemical associated with tire manufacturing and
      industrial wastewater, is a principal component of both fresh water and estuarine
      tire leachate, a neurotoxicant to larval sheepshead minnows (Cyprinodon
      variegatus) in in vivo estuarine studies. The neurotoxic potential of
      benzothiazole was investigated following in vivo and in vitro exposure of
      sheepshead minnows to 3.75, 7.5, 15, 30 and 60 mg/l benzothiazole. Following
      benzothiazole exposure, fish were evaluated for survival, growth and histological
      alterations. Fish mortality occurred after 5 days of exposure to 60 mg/l (LC50 =
      41.9). Significant decreases in larval growth were noted at all concentrations.
      Histologically, gills had cellular alterations but the central nervous system
      lacked the severe cellular damage seen in previous tire leachate exposure
      studies. Benzothiazole cytotoxicity to primary cultures of brain cells from
      sheepshead minnow and tilapia (Oreochromis niloticus) and two epithelial cell
      lines was evaluated using a tetrazolium salt assay (MTT) at 1 and 4 days. In
      vitro results indicate primary cultures of brain cells are less sensitive to
      benzothiazole than epithelial cell lines. Significant cytotoxicity to the
      epithelial cell lines was noted at 30 and 60 mg/l concentrations. Histologically
      and cytotoxicologically, the present study indicates that benzothiazole is a gill
      toxicant and not a neurotoxicant.

PMID- 11460701
TI  - Effects of the herbicide Roundup on the ultrastructural pattern of hepatocytes in
      carp (Cyprinus carpio).
AB  - Experimental studies were performed on healthy, 80-100 g carp (Cyprinus carpio).
      Fish were exposed by emersion in Roundup (205 mg of glyphosate/l or 410 mg of
      glyphosate/l) in concentrations of 40- to 20-fold lower than those used in
      practice. Electron microscopy revealed that the herbicide caused appearance of
      myelin-like structures in carp hepatocytes, swelling of mitochondria and
      disappearance of internal membrane of mitochondria in carp at both exposure
      concentrations. It means that Roundup was harmful to carp when used in applied
      concentrations. Results of these studies enhance our knowledge of ultrastructural
      pathomorphology of fish organs following exposure to Roundup.

PMID- 11460702
TI  - Pathology of fathead minnows (Pimephales promelas) exposed to chlorine dioxide
      and chlorite.
AB  - Fathead minnows (Pimephales promelas) were exposed to the biocide chlorine
      dioxide (0.13 and 0.19 mg l-1) for up to 12 h and to its primary decomposition
      product, chlorite (177 and 304 mg l-1), for up to 96 h followed by recovery
      periods of up to 14 days. Chlorine dioxide exposure produced dose-dependent gill
      pathology including epithelial lifting, hypertrophy, hyperplasia, lamellar
      fusion, and necrosis. Complete recovery, even in fish with severe hypertrophy and
      lamellar fusion, was achieved within 4 days. Chlorite did not produce gill
      pathology even at a lethal exposure level (304 mg l-1 for 96 h) but did elicit a
      chronic inflammatory response with a marked increase in circulating and fixed
      phagocytes within hematopoietic and vascular tissues. This study indicates that
      chlorine dioxide is approximately 1000 times more toxic to fathead minnows than
      chlorite. Further, exposure of fathead minnows to these distinct but related
      compounds is consistently associated with very different pathologies.

PMID- 11460703
TI  - Histopathology of the skin of UV-B irradiated sole (Solea solea) and turbot
      (Scophthalmus maximus) larvae.
AB  - Larval stages of two economically important flatfish, the sole (Solea solea) and
      turbot (Scophthalmus maximus) were exposed to ambient and elevated levels of UV
      B. Sole larvae, which naturally occur in the plankton in early spring,
      demonstrated skin lesions at elevated levels of UV-B. Histopathology of the sole
      revealed cellular changes in the integument, characteristic of sunburn damage,
      with a reduction in the size of mucus-secreting cells and an increased epidermal
      thickening, especially at the highest doses of UV-B (2.15 KJ bio eff/m2).
      Pigmentation in the sole is restricted to a few isolated melanocytes. The
      integrity of the heavily pigmented skin of turbot appeared to be unaffected by
      comparable doses of UV-B. Both species have protective mechanisms, which minimize
      the effects of naturally-occurring levels of UV-B. However, sole appear to be
      poorly adapted to accommodate any further increase in solar radiation.

PMID- 11460704
TI  - Gonadal cysts in spotted gar (Lepisosteus oculatus) from Bayou Trepagnier,
      Louisiana, USA.
AB  - Gonadal cysts of spotted gar (Lepisosteus oculatus), an air-breathing teleost
      commonly found in Louisiana waters, are described. Fish were collected from two
      sites: Bayou Trepagnier, a petroleum-contaminated site (30 males and 42 females),
      and Bayou Traverse, a control site (17 males and 15 females). After fish were
      evaluated for gross abnormalities, they were necropsied and the gonads, gonadal
      ducts, and gonadal cysts were evaluated histologically. Multilocular fluid-filled
      cysts were noted in the testes, or spermatic ducts of four spotted gars from the
      Bayou Trepagnier. Unilateral ovarian cystadenomas were present in one female from
      Bayou Trepagnier. No cysts were observed in the gonads of spotted gar from the
      control site.

PMID- 11460705
TI  - Pathology of the liver, kidney and gonad of flounder (Platichthys flesus) from a
      UK estuary impacted by endocrine disrupting chemicals.
AB  - The Mersey estuary is highly contaminated with xenobiotics compared to the nearby
      Dee estuary. Male flounder, a migratory flatfish caught in the Mersey frequently
      contains high blood concentrations of the oestrogen controlled, female protein
      vitellogenin, suggesting that Mersey flounder have been exposed to endocrine
      disrupting contaminants. Males caught from the Dee contain lower blood
      vitellogenin levels. Preliminary histopathological examination of 410 flounder
      from both estuaries, focuses on the liver, kidney and gonads. Hepatic tubular
      vacuolation, foci of cellular alteration, and hepatocellular tumours were seen.
      Renal and gonadal pathology included the presence of two Mersey fish with
      enlarged and abnormal glomeruli, three phenotypic male Mersey flounder with
      unilateral intersex gonads and one male with bilateral, abnormal ovarian
      follicular components in the testis. These initial results provide pathological
      evidence of xenobiotic exposure in flounder sampled from both estuaries.
      Preliminary findings from flounder sampled from Millport, an offshore site in
      Southwest Scotland, showed no histopathological evidence of xenobiotic exposure.

PMID- 11460706
TI  - Identification of an E3 ubiquitin-protein ligase in the softshell clam (Mya
      arenaria).
AB  - Softshell clams (Mya arenaria) were exposed to dioxin in controlled laboratory
      experiments in order to study their molecular response to dioxin exposure. A
      complementary DNA (cDNA) fragment with sequence similarity to E3 ubiquitin
      protein ligase appeared to be upregulated in dioxin-exposed clams compared to
      controls. E3 covalently ligates ubiquitin onto a protein, targeting it for
      degradation. Our findings suggest that the ubiquitin-mediated proteolytic pathway
      in the softshell clam may be activated by dioxin exposure. Because the clam E3
      predicted amino acid sequence is most similar to a specific vertebrate E3 protein
      (E6-AP), we hypothesize that dioxin may stimulate ubiquitin-mediated degradation
      of cell-cycle regulatory proteins, such as the tumor suppressor p53, which
      promotes cell proliferation. This pathway has been observed in human cervical
      cancer. Partial cDNA sequence of the clam E3 has been identified using the
      differential display polymerase chain reaction (ddPCR) and RACE (Rapid
      Amplification of cDNA Ends) PCR; the full-length sequence is currently being
      determined. Discovering the molecular mechanism(s) stimulated by dioxin exposure
      in this invertebrate model may contribute to a better understanding of the
      effects of dioxin on marine organisms.

PMID- 11460707
TI  - Effects of waterborne nitrite on phase I-II biotransformation in channel catfish
      (Ictalurus punctatus).
AB  - The effects of waterborne nitrite (3 mg/l NO2) on channel catfish were studied to
      evaluate changes in hematological parameters and phase I-II biotransformation in
      liver slices. Nitrite-exposed fish had significantly higher methemoglobin, blood
      and liver nitrite, and significantly lower pO2 than control fish. Total phase I
      mediated metabolism of 7-ethoxycoumarin (EC) was not altered in nitrite-exposed
      fish compared with control fish (291 +/- 43 and 312 +/- 20 pmol/mg/h,
      respectively). However, phase II glucuronosyltransferase-mediated metabolism of 7
      hydroxycoumarin (HC), both as a phase I metabolite of EC and as a parent
      substrate, was elevated in nitrite-exposed fish (204 +/- 17 and 1007 +/- 103
      pmol/mg/h, respectively) as compared to control fish (149 +/- 14 and 735 +/- 87
      pmol/mg/h) (P < 0.05). Sulfotransferase-mediated metabolism of HC (as a
      metabolite of EC and as a parent substrate) was not notably altered in nitrite
      exposed fish (95 +/- 16 and 617 +/- 33 pmol/mg protein/h, respectively) as
      compared with control fish (118 +/- 24 and 575 +/- 55 pmol/mg/h, respectively).
      These studies indicate that in vivo nitrite exposure and associated changes in
      hematological parameters do not appear to affect hepatic phase I EC
      biotransformation in channel catfish. However, subtle but significant changes in
      phase II glucuronidation, but not sulfation activity, were observed. The
      mechanism of these alterations is unclear. However, the data suggest that
      environmentally realistic concentrations of nitrite may affect the dynamics of
      conjugative metabolism in exposed fish.

PMID- 11460708
TI  - Sublethal effects of chromium-VI in the Asian clam (Potamocorbula amurensis).
AB  - Previously, we have shown that Asian clams (Potamocorbula amurensis) with highest
      metallic body burdens have highest prevalence of disease and lowest reproduction.
      The present study was designed to assess and validate potential sublethal
      toxicity of hexavalent chromium (Cr-VI) in clams under controlled laboratory
      exposure. For 7 days, three replicates of clam (n = 10 per replicate) were
      exposed to aqueous solution containing 0.00, 0.92, 8.40, or 25.6 mg l-1 of Cr-VI
      at 15 degrees C and 15 g l-1 salinity. Mortality reached 100% in the 25.6 mg l-1
      group within 7 days. There was no significant difference in mortality among the
      control, 0.92, and 8.40 mg l-1 groups. Western blot analyses revealed
      significantly elevated stress protein hsp70 levels in the 8.40 mg l-1 treatment
      group. Histopathologic analyses revealed mild digestive gland (DG) atrophy in the
      control group. Clams exposed to 0.92 mg l-1 Cr-VI showed moderate DG atrophy,
      moderate granulomatous inflammation and necrosis in DG, ovary and testis. Lesions
      observed in the 8.40 mg l-1 treatment group included severe DG atrophy, severe
      granulomatous inflammation and necrosis in byssal gland, DG, gill, kidney, ovary
      and testis. In gills and testes of treated groups, apoptotic cells outnumbered
      mitotic cells. In addition, gills from clams in the 8.40 mg l-1 group showed
      enhanced hsp70 staining. Our studies support a cause-effect relationship between
      contaminants and reduced health in Asian clams and indicate the DGs, gills, and
      reproductive organs are principal targets of Cr-VI toxicity at sublethal
      concentrations. Results from this study suggest that Cr-VI may have played a role
      in the increased incidence of diseased clams seen in previous studies and these
      adverse effects may be working to decrease clam populations at sites with highest
      metallic contamination in the San Francisco Bay Estuary.

PMID- 11460709
TI  - Tissue and cellular alterations in Asian clam (Potamocorbula amurensis) from San
      Francisco Bay: toxicological indicators of exposure and effect?
AB  - The US Geological Survey has reported the presence of a metal contamination
      gradient in clam tissues, decreased condition indices, and irregular reproductive
      patterns have been reported in the Asian clam, Potamocorbula amurensis, from San
      Francisco Bay. If metals are driving the observed patterns in the field, then
      biomarkers of exposure, and possibly deleterious effect, should show a
      corresponding gradient. In this study, biomarkers from sub-cellular to tissue
      levels of biological organization were assessed in P. amurensis collected from
      the Bay or exposed to cadmium in the laboratory. Cellular and tissue alterations
      were assessed using histopathology and enzyme histochemistry (EH). Alterations in
      the ovary, testis, kidney, and gill tissues were most common at the most
      contaminated station when data were averaged over a 12-month sampling period. EH
      analysis indicated decreased active transport, energy status, and glucose
      oxidation in kidney and digestive gland at the most contaminated site which may
      indicate a decreased potential for growth. Ovarian lesions observed in feral
      Asian clams were experimentally induced in healthy clams by cadmium exposure in
      laboratory exposures. Our results suggest a contaminant etiology for tissue
      alterations.

PMID- 11460710
TI  - Distribution and inducibility of P-glycoprotein in the catfish:
      immunohistochemical detection using the mammalian C-219 monoclonal.
AB  - Mounting evidence suggests that the P-glycoprotein (pgp) efflux pump may be a
      modulator of bioavailability and a mode of excretion for xenobiotics.
      Immunohistochemistry was utilized to examine the distribution and inducibility of
      a pgp like protein in catfish. Immunoreactivity to the MDR C-219 monoclonal
      antibody was noted primarily in bile canaliculi or bile preductules of the liver,
      discrete areas of the extratubular region of the kidney and the columnar
      epithelia of the intestine. Regional differences in pgp content were noted in the
      intestine with the distal region containing greater pgp levels than the proximal
      intestine. Dietary administration of vincristine, a prototypic pgp inducer and
      beta-naphthoflavone an Ah agonist resulted in induction of the C-219
      immunoreactivity in the liver and the distal intestine. These results are
      consistent in location and inducibility with pgp like proteins and support a
      possible relationship to xenobiotic absorption and/or excretion in the catfish.

PMID- 11460711
TI  - Multidrug resistance in the embryos and larvae of the mussel Mytilus edulis.
AB  - Cells exhibiting the multidrug resistance (MDR) phenotype demonstrate a decreased
      intracellular drug accumulation due to an active outward transport and decreased
      intracellular flux. This study demonstrates the inhibition of MDR in mussel
      (Mytilus edulis) embryos and larvae based on a simple bioassay. The development
      of embryos was assessed and abnormalities identified at key stages of
      development, including gastrulation, trochophore and prodissoconch stages. The
      incidence of developmental abnormalities was significantly increased in the
      presence of vinblastine, MMS, chloroquine, mitomycin-C, cadmium chloride and
      colchicine, compared to clean seawater. Consistently, there was a further
      increase in the number and severity of deformities observed when each toxin was
      added in the presence of verapamil. Larval growth was also significantly impaired
      in the presence of verapamil. Increased accumulation of fluorescent MDR dyes,
      such as rhodamine B, has been measured and shown to be verapamil sensitive. This
      bioassay encompasses a period of intense cellular activity during which the
      impairment of a number of critical processes results in abnormal growth and
      development.

PMID- 11460712
TI  - Stability of lysosomal and cell membranes in haemocytes of the common mussel
      (Mytilus edulis): effect of low temperatures.
AB  - Expanding industrial activities in the Arctic require an urgent assessment of the
      toxicity of chemicals at low temperatures. Organisms acclimatized to low
      temperature exhibit specific adaptations. For example, the amount of unsaturated
      lipids is increased to maintain the fluidity of the cell membranes. It has been
      hypothesized that such temperature-induced alterations in membrane lipid
      composition may affect the stability of lysosomal and cell membranes in the
      common mussel, Mytilus edulis, an organism exposed to seasonal temperature
      extremes. As mussels may be exposed to petroleum compounds along industrialized
      coastlines, we tested the combined effects of exposure to low temperature and the
      petroleum compound, phenanthrene, on haemocyte membrane stability. Test animals,
      acclimated to either 0 or 10 degrees C, were exposed to phenanthrene (0 = control
      or 500 micrograms l-1) and haemocytes were examined using the neutral red
      retention assay (lysosomal stability) and a fluorescence assay (cell membrane
      stability). At 0 degree C, lysosomal and cell membranes from uncontaminated
      mussels were destabilized compared with 10 degrees C (P = 0.0005). No significant
      effects (P > 0.05) of phenanthrene were detected at either temperature. Possible
      mechanisms underlying membrane destabilization include a weaker physical
      resistance of the membrane due to a higher amount of unsaturated lipids, a
      potentially higher level of reactive oxygen radicals at low temperature and the
      higher susceptibility of unsaturated lipids to oxidative stress. More work is
      required to better understand the consequences of this membrane destabilization
      at low temperature on the susceptibility of the organism to pollutants.

PMID- 11460713
TI  - A survey of in vivo benzo[alpha]pyrene metabolism in small benthic marine
      invertebrates.
AB  - A micro-extraction technique was used to examine in vivo polycyclic aromatic
      hydrocarbon (PAH) metabolism in 10 small invertebrate species exposed to
      sediments amended with 3H-benzo[alpha]pyrene (BaP). Phyla examined included
      Mollusca (Hydrobia totteni, Ilyanassa obsoleta, Yoldia limatula, and Gemma
      gemma), Annelida (Nereis succinea, Pectinaria gouldii, Haploscolopolous sp., and
      Capitella sp. 1) and Arthropoda (Edotea triloba, and Gammarus mucronatus).
      Organisms were exposed to BaP-labeled sediments, harvested, and parent BaP
      separated from all polar metabolites by liquid extraction The percent of BaP
      derived radio-activity present as polar metabolites ranged from 96% for N.
      succinea to 7% for P. gouldii. Wide ranges in metabolic capability were also
      observed between species in the other two phyla examined. Reverse-phase HPLC
      analysis of extracts of representative species from each phyla indicated that all
      these organisms form bay region metabolites, with two species forming the 7,8
      dihydrodiol (N. succinea and G. mucronatus). In light of the high variability in
      metabolic capability observed within each phylum, species-specific information on
      metabolic ability should be obtained before assessing bioaccumulation, critical
      body burdens, or trophic transfer of PAHs in invertebrates.

PMID- 11460714
TI  - Protein expression signatures identified in Mytilus edulis exposed to PCBs,
      copper and salinity stress.
AB  - Applied to environmental toxicology, proteome analysis may be used to isolate
      chemical-specific protein expression signatures (PES). In this project specific
      PES were isolated in mussels, Mytilus edulis, from the Baltic Sea subjected in
      the laboratory to treatment with copper (70 ppb), Aroclor 1248 (1 ppb), and to
      lowered salinity. Four mussels in each treatment group were acclimated in the
      laboratory for 24 h before beginning the 7-day exposure. Whole body tissue was
      homogenized and separated using two-dimensional gel electrophoresis. The protein
      gels were scanned to TIFF files and compared using MELANIE II 2D gel analysis
      software (BioRad). Protein expression signatures including proteins induced and
      repressed by exposure were isolated for each treatment group. The specificity of
      PES due to environmental changes shows promise in bioindication, toxicity testing
      and in helping identify possible toxicity mechanisms.

PMID- 11460715
TI  - Effects of PCBs sorbed to algal paste and sediments on the stress protein
      response (HSP70 family) in the eastern oyster, Crassostrea virginica.
AB  - This study examined the stress protein response (HSP70 family) of reproductively
      inactive oysters fed 0.7 g algal paste containing 0, 0.35 and 3.5 micrograms
      polychlorinated biphenyls (PCBs) daily. A second set of treatment groups
      investigated the combined effect of PCBs and sediments (0.3 g sediments daily per
      oyster) on HSP70 response. After 8 weeks of PCB exposure, oyster tissues (mantle
      and gill) were sampled and analyzed for HSP70. Preliminary results did not show a
      significant effect in HSP70 response in oysters fed PCB sorbed to algal paste,
      albeit PCBs accumulated up to 1342 ng/g dry weight in the mantle, and up to 180
      ng/g dry weight in gill tissues. However, the addition of sediments caused a
      significant increase in HSP70 levels of gills and mantle, although the mantle was
      less sensitive to the sediments.

PMID- 11460716
TI  - In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts
      in fish.
AB  - Benzo[a]pyrene (BaP), a procarcinogenic polycyclic aromatic hydrocarbon (PAH), is
      bioactivated to BaP diol-epoxides (BPDEs) that can form adducts with DNA and
      blood proteins. We report here for the first time the in vivo formation of
      adducts between BPDE and plasma albumin (Alb) from two fish species
      experimentally exposed to BaP. Brook trout (Salvelinus fontinalis) received
      either a single i.p. dose (10 mg/kg) or two separate i.p. doses (25 mg/kg; 7 days
      apart) of BaP, and blood was collected 2 (single exposure) or 3 (multiple
      exposure) days post-treatment. Arctic charr (Salvelinus alpinus) received 10 i.p.
      doses (3 mg/kg; a single dose every 6 days), and blood was collected 2 days after
      the second, sixth, and 10th injections. BPDE-Alb adducts were measured by an
      improved HPLC/fluorescence method developed to detect and quantify BaP-tetrols
      released after acid hydrolysis of adducted Alb. HPLC/fluorescence chromatograms
      of Alb from BaP-treated fish revealed only BaP-tetrol I-1, thus indicating the
      formation of adducts exclusively via the (+)-anti-BPDE metabolite. Levels of (+)
      anti-BPDE-Alb adduct ranged from 0.68 to 19.6 ng of tetrol I-1 per gram of Alb.
      Notably, adduct level was not related to BaP dose and there was no accumulation
      of adducts with repeated exposure, which may indicate a very short half-life (< 2
      days) of plasma Alb in fish. The data suggest that BPDE-Alb adducts in fish could
      be useful as a non-destructive biomarker of recent exposure to bioactivated BaP.

PMID- 11460717
TI  - Differential expression of alpha-like glutathione S-transferase (GST) isoforms in
      catfish intestine.
AB  - Previous studies suggested that dietary composition affected glutathione S
      transferase (GST) activity in catfish intestine, and this activity varied along
      the intestine. In this study, catfish were fed a semi-purified diet or a
      commercial chow for at least 2 weeks. GST activity, percent protein cross
      reacting with anti-catfish GST pi antibody, and immuno-cross-reactivity with
      antibodies specific for human alpha, mu, pi and theta class GSTs were determined
      in cytosol prepared from sections of proximal, medial, and distal intestine. The
      bulk of GST activity with 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid,
      and the percent protein cross-reacting with anti-catfish GST pi were in the more
      proximal segments and dropped off distally in the two diet groups. The percent of
      cross-reacting GST protein in the proximal section of fish fed on commercial chow
      was significantly higher (4.3 +/- 1.7%) than in fish fed purified diet (2.3 +/-
      0.2%). Further Western blot analysis revealed a differential expression of GST
      isoforms only in the distal segment of fish fed commercial chow that recognized
      human anti-alpha GST antibody. Distal intestinal segments of catfish exposed to
      3,3',4,4'-tetrachlorobiphenyl (TCB) and beta-naphthoflavone (BNF) also revealed
      expression of distinct alpha-like GST isoforms. Results strongly suggest the
      distal segment as a site for potential biomarkers for polycyclic aromatic
      hydrocarbon (PAH)- and co-planar polychlorinated biphenyl (PCB)-type
      contaminants.

PMID- 11460718
TI  - Environmental monitoring using acetylcholinesterase inhibition in vitro. A case
      study in two Mexican lagoons.
AB  - Cholinesterase inhibition is considered a specific biomarker of exposure and
      effect for organophosphorous pesticides. Its use for monitoring has been
      hindered, particularly in tropical countries where organophosphates are widely
      used for malaria and dengue control, because of the frequent lack of suitable
      controls. An in vitro technique is proposed as a biochemical method for
      monitoring pollutant mixtures in sediment toxicity tests. Brain homogenate from
      the fish Oreochromis niloticus is used as the enzyme source. Optimum incubation
      time, extraction solvent and effect of crude oil on acetylcholinesterase (AChE)
      are reported. The method described was used in sediments from two Mexican
      lagoons, located in an oil extraction area where pesticides are used in
      agriculture and vector control campaigns. AChE inhibitions from 3 to 21% were
      found in these lagoons, even in the presence of high concentrations of petroleum.

PMID- 11460719
TI  - Immunodetection of hepatic peroxisomal PMP70 as an indicator of peroxisomal
      proliferation in the mummichog, Fundulus heteroclitus.
AB  - Peroxisomes are important sites for beta-oxidative fatty acid metabolism and
      peroxidative detoxification. Agents causing peroxisomal proliferation have been
      associated with reproductive and developmental toxicity and hepatocarcinogenesis.
      Female mummichog (Fundulus heteroclitus) were exposed to waterborne 2,4
      dichlorophenoxyacetic acid (2,4-D), a model peroxisome proliferator, at sublethal
      concentrations of 0.01, 0.10, and 1.00 ppm or dimethyl sulfoxide (DMSO) vehicle
      for 7, 14, or 21 days. A polyclonal antibody to rat PMP70 protein (70 kDa
      peroxisomal membrane protein, a major component of peroxisomes and member of the
      ABC transporter superfamily) was used for Western blotting after sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to determine possible
      peroxisome proliferation. Significant increases of an approximately 70-kDa
      protein band recognized by anti-PMP70 were observed on all days, especially at
      the highest exposure concentration. The data suggest that immunoassay of PMP70 is
      a useful biomarker assay for peroxisome proliferation, and may be applicable to a
      wide range of species. The response also suggests that this assay could be used
      for measuring chronic exposures to environmental peroxisome proliferating agents.

PMID- 11460720
TI  - Development of hepatic CYP1A and blood vitellogenin in eel (Anguilla anguilla)
      for use as biomarkers in the Thames Estuary, UK.
AB  - The potential of eel (Anguilla anguilla) as a monitoring species for the Thames
      Estuary, UK, was examined. Hepatic cytochrome P4501A [7-ethoxyresorufin O
      deethylase (EROD) activity] and blood vitellogenin (Western analysis) were
      investigated as biomarkers of exposure to, respectively, organic contaminants and
      to contaminants showing estrogenic activity. Hepatic microsomal EROD activities
      in A. anguilla from seven sites in the Thames Estuary in May 1998 varied three
      fold (111 +/- 24 to 355 +/- 42 pmol min-1 mg protein-1) (mean +/- S.E.M.) and
      showed correlation with salinity; however, the latter relationship was not
      maintained at other times of the year. The range of EROD activities was two- to
      eight-fold higher than the 37 +/- 8 pmol min-1 mg-1 for A. anguilla from the
      relatively clean Tamar Estuary. beta-Naphthoflavone treatment (5 mg kg-1 wet wt.;
      2 days) of Thames A. anguilla produced a two-fold increase in hepatic microsomal
      EROD activity. Comparing the Thames EROD data with those for A. anguilla from
      well-characterised contaminated sites in the Netherlands (Van der Oost, R.,
      Goksoyr, A., Celander, M., Heida, H., & Vermeulen, N. P. E. 1996. Aquatic
      Toxicology, 36, 189-222), the Thames is suggested to be moderately impacted by
      polycyclic aromatic hydrocarbons and related contaminants. 17-beta-Estradiol
      treatment produced the appearance of a plasma protein of 211 Kd app. mol. wt.
      (recognised by antibodies to vitellogenin of Morone saxatilis), but putative
      vitellogenin could not be detected in A. anguilla from selected sites in the
      Thames Estuary.

PMID- 11460721
TI  - Flounder health status in the Seine Bay. A multibiomarker study.
AB  - The Seine Bay is used as a pilot area to assess the usefulness of monitoring
      programmes using a suite of biological measurements. These biomarkers included
      ethoxyresorfin-O-deethylase (EROD) and acetylcholinesterase (AChE) activities,
      multixenobiotic resistance (MXR) protein expression level assessment and gonad
      histopathology. Samples of European flounder collected in three sites close to
      the Seine Estuary in late September 1998 showed that 8% of the males were
      intersex, i.e. had gonads with both male and female tissues. Another 10% of
      individuals, identified as male by morphological observation during sampling,
      showed only female tissues on histological sections. These dramatic changes were
      associated with different patterns of EROD activity, MXR expression or AChE
      activity inhibition that might reflect shorter time effects of xenobiotics and
      constitute a starting point to integrate biological responses for the assessment
      of the health status of flounder in the Seine Bay.

PMID- 11460722
TI  - Spatial profiles of hsp70 proteins in Asian clam (Potamocorbula amurensis) in
      northern San Francisco Bay may be linked to natural rather than anthropogenic
      stressors.
AB  - Multi-year investigations in northern San Francisco Bay by United States
      Geological Survey have linked reduced condition indices in populations of Asian
      clam (Potamocorbula amurensis) with elevated cadmium tissue concentrations. Our
      study seeks to determine whether levels of hsp70 proteins in P. amurensis can be
      correlated with these findings, and/or are related to histopathologic alterations
      and concentrations of metallothionein-like proteins. Here we present our results
      on stress proteins in clams collected monthly from four field stations between
      July 1996 and January 1998. In addition, animals were exposed in the laboratory
      to a range of salinities. Stress proteins were analyzed by Western blotting using
      monoclonal antibodies. Hsp70 protein levels in field-collected clams were
      significantly higher at the seaward (high salinity/low cadmium) stations (12.5,
      8.1) than at the landward (low salinity/high cadmium) stations (6.1, 4.1).
      Laboratory studies showed that clams exposed to 0.1 ppt salinity had markedly
      lower hsp70 levels than clams exposed to higher salinities. In view of our
      previous laboratory studies showing that cadmium induces hsp70 in P. amurensis,
      our present results indicate that reduced hsp70 protein levels in field-collected
      clams may be linked to salinity effects rather than cadmium tissue
      concentrations.

PMID- 11460723
TI  - Toxicity of sediments from Bahia de Chetumal, Mexico, as assessed by hepatic EROD
      induction and histology in nile tilapia Oreochromis niloticus.
AB  - The effect of environmental pollutants present in sediments obtained from Bahia
      de Chetumal, a bay on the border between Mexico and Belize, was studied in nile
      tilapia (Oreochromis niloticus) intraperitoneally injected with sediment extracts
      from six different sites of the Bay. Sediment samples used for the study
      contained a variety of organic chemicals such as organochlorine pesticides,
      polychlorinated biphenyls (PCBs) and polynuclear aromatic hydrocarbons (PAHs).
      Total cytochrome P-450 and EROD activity were measured in fish liver.
      Haematological and histological analyses were also carried out. Hepatic P-450
      content in treated fish increased from 43 to 240%, and EROD activity from 85 to
      160% compared to controls. Extracts from two sampling sites inhibited EROD
      activity. There were positive significant correlations between P-450 content and
      the levels of PCBs 44 and 128. EROD activity correlated to HCB, op'-DDE, pp'-DDE,
      pp'-DDD, mirex and PCB 18 concentrations. Blood examination showed cell
      degeneration and binucleated leukocytes with abnormal chromatin. Extract
      treatment also resulted in foci of hyperplasia on the basement of gill lamellae,
      hypertrophy and oedema in gills and liver necrosis. Control fish showed no
      abnormalities. The results demonstrate that sediments from Bahia of Chetumal have
      the potential to cause histopathological, haematological and biochemical
      alterations in fish. The administration of sediment extracts to fish may serve as
      a useful test to screen the toxicity of sediments from different areas.

PMID- 11460724
TI  - The evolution of aryl hydrocarbon signaling proteins: diversity of ARNT isoforms
      among fish species.
AB  - The aryl hydrocarbon receptor nuclear translocator (ARNT) mediates aryl
      hydrocarbon signaling and toxicity by dimerizing with the ligand-activated aryl
      hydrocarbon receptor (AHR), forming a complex that binds specific DNA elements
      and alters transcription of target genes. Two genes encode different forms of
      ARNT in rodents: ARNT1, which is widely expressed, and ARNT2, which exhibits a
      very restricted expression pattern. In an effort to characterize aryl hydrocarbon
      signaling mechanisms in fishes, we previously isolated an ARNT cDNA from Fundulus
      heteroclitus and discovered that this species expresses ARNT2 ubiquitously. This
      situation differs not only from mammals, but also from rainbow trout, which
      expresses a divergent ARNT gene that we hypothesized was peculiar to salmonids
      (rtARNTa/b). In this communication, we examine the ARNT sequences of multiple
      fish species, including a newly isolated cDNA from scup (Stenotomus chrysops).
      Our phylogenetic analysis demonstrates that zebrafish ARNT, like the Fundulus
      protein, is an ARNT2. Contrary to expectations, the scup ARNT is closely related
      to the rainbow trout protein, demonstrating that the existence of this ARNT
      isoform predates the divergence of salmonids from the other teleosts. Thus,
      different species of fish express distinct and highly conserved isoforms of ARNT.
      The number, type, and expression pattern of ARNT proteins may contribute to
      interspecies differences in aryl hydrocarbon toxicity, possibly through distinct
      interactions with additional PAS-family proteins.

PMID- 11460725
TI  - Endocrine disruption: thyroid dysfunction in mummichogs (Fundulus heteroclitus)
      from a polluted habitat.
AB  - Mummichogs (Fundulus heteroclitus) from Piles Creeks (PC), New Jersey (a polluted
      site), are sluggish and show poorer prey capture and predator avoidance than
      reference fish from Tuckerton (TK). The behavioral dysfunction of the PC fish may
      be associated with thyroid impairment due to endocrine disruption. In this study,
      we compared thyroid histology and thyroid hormones in the two populations and
      determined experimentally whether the polluted environment could alter thyroid
      hormone levels. PC fish had larger thyroid follicles, greater follicle cell
      heights, and contained higher plasma thyroxine (T4) levels than TK fish. However,
      there were no significant differences in either plasma or tissue triiodothyronine
      (T3). TK fish held in simulated PC environments had higher plasma T4 and lower
      plasma T3 than field-sampled fish. PC fish held in clean water had lower plasma
      T4 and T3 than field-sampled fish. In either case, there was no significant
      difference in tissue T3 content. The contaminants in PC alter thyroid structure
      and function, which may relate to the behavioral differences between fish from
      the polluted and reference sites.

PMID- 11460726
TI  - Altered glutathione S-transferase catalytic activities in female brown bullheads
      from a contaminated central Florida lake.
AB  - Brown bullheads (Ameriurus nebulosus) are a demersal freshwater species that can
      be found in a number of polluted ecosystems. The purpose of the present study was
      to determine the overall capacity for in vitro glutathione S-transferase (GST)
      detoxification by brown bullheads, and to see if bullhead GST catalysis was
      altered in bullheads from a polluted site. Brown bullhead liver cytosolic GSTs
      catalyzed the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) over a large
      range of substrate concentrations, with apparent Km and Vmax for CDNB at fixed
      nucleophile (glutathione, GSH) concentrations of 1.8-1.9 mM and 12.1-14.6 mumol
      CDNB conjugated/min/mg, respectively. Bullhead GSTs were also highly active
      toward other substrates such as ethacrynic acid (ECA), delta 5-androstene-3,17
      dione (ADI), and nitrobutyl chloride (NBC). Initial rate GST catalytic activities
      toward CDNB, NBC, ECA, and ADI were significantly lower in female bullheads from
      a contaminated lake (Lake Apopka Marsh) as compared to female bullheads
      inhabiting a nearby control site (Lake Woodruff). No site differences were
      observed with respect to male bullhead GST activities. These studies suggest that
      brown bullheads efficiently carry out GST conjugation of diverse electrophilic
      substrates. However, bullhead GST catalysis may be compromised in bullheads
      inhabiting polluted ecosystems.

PMID- 11460727
TI  - Seasonal variation in mussel Mytilus edulis digestive gland cytochrome P4501A-
      and 2E-immunoidentified protein levels and DNA strand breaks (Comet assay).
AB  - Mytilus edulis digestive gland microsomes were prepared from indigenous
      populations sampled from a clean reference site (Port Quin) and an urban
      industrial contaminated site (Blackpool) in the UK. Samples were collected in
      March/April, May, August and December 1998. Western blot analysis was performed
      using polyclonal antibodies to fish CYP1A and rat CYP2E using partially purified
      M. edulis CYP as a positive control, to aid identification. CYP1A- and CYP2E
      immunopositive protein levels showed different site-specific seasonal variation
      with higher levels of CYP2E determined in May (P < 0.05). At both sites, lower
      levels of CYP1A-immunopositive protein but not CYP2E-immunopositive protein were
      observed in the samples collected in December (P < 0.05). This correlated with
      lower levels of nuclear DNA damage (Comet assay expressed as per cent tail DNA)
      observed in December compared to August (P < 0.05).

PMID- 11460728
TI  - Biochemical responses in farmed mussel Perna perna transplanted to contaminated
      sites on Santa Catarina Island, SC, Brazil.
AB  - The effects of contaminants on the biochemical parameters of the intensively
      farmed mussel Perna perna, are unknown. The aim of this study was to compare
      biochemical responses in mussels held in clean and contaminated sites in Santa
      Catarina Island, Brazil. Mussels were transplanted from a farming area, Ratones
      Grande Island (RGI), to two contaminated sites, Itacorubi (ITAC) and Hercilio Luz
      Bridge (HLB). A reference group was kept at RGI. After 150 and 180 days of
      exposure, the digestive glands of the mussels were analyzed for catalase, glucose
      6-phosphate dehydrogenase (G6PDH) and glutathione S-transferase (GST) activities.
      No changes were observed in the catalase activity, in both periods. Low G6PDH
      activity was observed in mussels transplanted for 150 days at the ITAC site.
      Increased GST activity was observed in mussels from ITAC and HLG sites after 180
      days. These responses are probably related to the augmented discharges of
      domestic effluents associated with elevated rainfall index.

PMID- 11460729
TI  - Biomarkers and trace metals in the digestive gland of indigenous and transplanted
      mussels, Mytilus galloprovincialis, in Venice Lagoon, Italy.
AB  - The aim of this study was to investigate the cellular and biochemical response of
      mussels, Mytilus galloprovincialis, transplanted from a relatively pristine site
      to a polluted one and vice versa in the Lagoon of Venice (northeast of Italy) and
      to apply auto-metallography, a rapid and sensitive histochemical technique, to
      determine the bio-available fraction of heavy metals accumulated in the body
      tissues of organisms. Animal digestive glands have been used for morphological
      analyses (lysosomal volume, surface and numerical density, mean epithelial
      thickness, mean diverticular and luminar radius), autometallographical black
      silver deposits quantification and biochemical assays (superoxide dismutase and
      catalase activity). Furthermore, heavy metal content was determined by atomic
      absorption spectrophotometry (AAS) using standard procedures. The overall results
      indicate a direct influence of the environment in the thinning of the digestive
      cells and in the increasing number of lysosomes in mussels from the more polluted
      site. These data are in agreement with the metal content in digestive cell
      lysosomes as determined by autometallography, whereas AAS measurements show less
      significant differences.

PMID- 11460730
TI  - Biochemical and histochemical responses to environmental contaminants in clam,
      Tapes philippinarum, transplanted to different polluted areas of Venice Lagoon,
      Italy.
AB  - In this study the clam, Tapes philippinarum, a filter-feeding bivalve living in
      soft bottoms, was used to investigate the water/sediment pollution in Venice
      Lagoon (Venice, Italy), a heavily urbanised and industrialised area. To this end,
      clams collected from indigenous populations in a clean farming area (Val Doga)
      were transplanted into a relatively low contaminated site (Palude della Rosa) and
      in a heavily polluted area (Porto Marghera), for 5 weeks. A range of possible
      induced stress indices were measured, on the basis of potential toxicity
      mechanisms, including specific enzymatic activities [Bap hydroxylase and NADPH
      cytochrome c reductase, superoxide dismutase, catalase, glutathione peroxidase
      and propionaldehyde dehydrogenase (PDH)] and general cellular responses
      (lysosomal latency). Moreover, chemical analyses (polychlorinated biphenyls,
      polycyclic aromatic hydrocarbon, DDTs) were carried out on sediments and animal
      tissues at the beginning and end of the transplantation experiments. The chemical
      results show an active bio-accumulation activity from sediment in clams
      translocated to the most polluted area. Correspondingly, biological data indicate
      marked effects on PDH activity and latency in T. philippinarum from the same
      site. In contrast, no similar pattern has been observed in the other considered
      indices, possibly due to antagonistic effects of the complex contaminant mixture
      present in the environment.

PMID- 11460731
TI  - Immune response of greenback flounder Rhombosolea tapirina after exposure to
      contaminated marine sediment and diet.
AB  - Non-specific immune response of greenback flounder, Rhombosolea tapirina, exposed
      to contaminated marine sediments was examined. Reference sediments from Port
      Sorell and contaminated sediments from Deceitful Cove, Tasmania, Australia were
      investigated. Hatchery-reared flounder were exposed to reference sediment,
      contaminated sediment or contaminated sediment and diet for 6 weeks. Phagocytic
      capacity and lysozyme response in flounder were examined on cessation of exposure
      trial. Significant differences were found in phagocytic capacity and lysozyme
      response between treatments. Exposure to contaminated sediment, irrespective of
      diet or benthic disturbance elicited inhibition of phagocytic efficiency in
      flounder. Disturbance of contaminated sediment stimulated lysozyme activity. The
      immune response in flounder indicates potential immunotoxicity of sediment from
      Deceitful Cove.

PMID- 11460732
TI  - The effect of PCBs on glycogen reserves in the eastern oyster Crassostrea
      virginica.
AB  - Recent declines in Chesapeake Bay oyster populations have been attributed to
      disease, and reduced water quality from pollution. The stress associated with
      pollutant exposure may reduce energy available for growth and reproduction.
      Polychlorinated biphenyls (PCBs) are lipophilic contaminants that may potentially
      affect mobilization of lipid reserves, increasing reliance on glycogen stores,
      which could otherwise be utilized to supply energy for gametogenesis. Thus, PCBs
      may indirectly affect glycogen stores in oysters in a deleterious manner. To test
      for this effect, reproductively inactive oysters were exposed to PCBs by feeding
      individuals 0.7 g of algal paste containing 0, 0.35, or 3.5 micrograms PCBs daily
      for 8 weeks. Additionally, a group of oysters was exposed to PCBs (0, 0.35, and
      3.5 micrograms) plus 0.3 g of non-toxic artificial sediment to examine
      interactive effects of sediment particles and PCBs. Adductor muscle, mantle, and
      gonadal tissues were analyzed for glycogen content. Results suggest that glycogen
      content is reduced in the adductor muscle with increasing PCB exposure, but there
      are no effects of PCBs in the mantle and gonadal tissues.

PMID- 11460733
TI  - Impact of the Sea Empress oil spill on lysosomal stability in mussel blood cells.
AB  - Coastal zones are among the most productive and vulnerable areas on the planet.
      An example of impact on these fragile environments was shown in the case of the
      "Sea Empress" oil tanker, which ran aground in the Bristol Channel in 1996,
      spilling 72,000 tons of "Forties" crude oil. The objective was to investigate the
      sub-lethal cellular pathology and tissue hydrocarbon contamination in marine
      mussel populations, 4 months after the initial spill, using the neutral red
      retention (NRR) assay for lysosomal stability in blood cells. NRR was reduced in
      mussels, and indicative of cell injury, from the two sites closest to the spill
      in comparison with more distant and reference sites. Lysosomal stability was
      inversely correlated with polycyclic aromatic hydrocarbon concentrations in
      mussel tissues. Reduced lysosomal stability has previously been shown to
      contribute to impaired immunocompetence and to autophagic loss of body tissues.
      The use of this type of technique is discussed in the context of cost-effective,
      ecotoxicological tools for Integrated Coastal Zone Management.

PMID- 11460734
TI  - Protein expression signatures and lysosomal stability in Mytilus edulis exposed
      to graded copper concentrations.
AB  - Protein expression and lysosomal stability were observed in Mytilus edulis
      exposed to 0, 20, 40, 60, and 80 ppb copper sulfate for 24 h in a static exposure
      system. Haemolymph was removed from each mussel and analyzed for lysosomal damage
      using the Neutral Red retention assay expressed as the ratio of lysosomal size to
      cell area, the lysosomal destabilization ratio. Gill tissue from the same
      individuals was dissected, homogenized and the proteins extracted and then
      separated using two-dimensional gel electrophoresis. Two-dimensional protein maps
      from each concentration were analyzed using MELANIE II 2D gel analysis software
      (Biorad). Lysosomal damage increased with each dosage, with LDRs ranging from
      0.18 +/- 0.01 at 0 ppb copper sulfate to 0.32 +/- 0.11 at 80 ppb copper sulfate.
      Orthogonal comparisons showed that the control, 20 and 40 ppb classes together
      differed significantly (P < 0.05) from the 60 and 80 ppb classes together.
      Specific protein expression signatures were identified at each dosage.

PMID- 11460735
TI  - Etiologies, observations and reporting of estuarine finfish lesions.
AB  - Lesions in estuarine finfish are associated with a variety of organisms including
      parasites and bacterial, viral, and fungal infectious agents. In addition,
      trauma, suboptimal water quality, and other abiotic stress factors may result in
      the loss of homeostasis. We have observed solitary ulcerative lesions on menhaden
      sampled from the Chesapeake Bay, Maryland, the Pimlico River, North Carolina, and
      the St. Johns River, Florida. Histologically, the lesions demonstrated a marked
      chronic inflammatory infiltrate and granulomas in response to fungal hyphae
      throughout large areas of exposed necrotic muscle. Gram-negative rod-shaped
      bacteria were also observed in the lesions, a common finding in ulcers of aquatic
      organisms. Similar observations in menhaden and other species have been described
      previously in the literature as ulcerative mycosis, mycotic granulomatosis, red
      spot disease, and epizootic ulcerative syndrome. Despite the many different known
      causes of fish lesions, the popular press and the scientific literature have
      recently emphasized Pfiesteria piscicida and other Pfiesteria-like
      dinoflagellates (and their bioactive compounds) as the primary causative agent
      for finfish lesions, particularly mycotic granulomatous ulcers in Atlantic
      menhaden. While some laboratory data suggest that Pfiesteria may play a role in
      field-observed lesions, much more cause-and-effect evidence is needed to
      determine the importance of other risk factors, both alone or and in combination
      with Pfiesteria. In order to better understand the etiology of lesion initiation
      and progression in estuarine finfish, accurate assessments of environmental
      conditions collected on appropriate temporal and spatial scales, and fish
      morphological indicators consistent with gross and histological pathologic
      terminology, should be used for reporting fish lesion observations and kills.
      Further, this outlook will help to avoid bias and may foster a broader
      perspective for examining the health of estuarine systems in general.

PMID- 11460736
TI  - Paralytic shellfish poisoning toxins induce xenobiotic metabolising enzymes in
      Atlantic salmon (Salmo salar).
AB  - Paralytic shellfish poisoning (PSP) toxins have been implicated as the causative
      agent of a number of fish kills. Exposure experiments indicate that fish are
      susceptible to PSPs by intraperitoneal (i.p.) and oral administration, while
      sampling of fish affected by toxic blooms reveals that these toxins can be
      accumulated. In spite of the potential impact to marine fisheries, little
      research has been conducted on the potential metabolism and detoxification of
      PSPs in marine fishes. Previous work by this group has shown that the xenobiotic
      metabolising enzyme (XME) cytochrome P-450 (CYP1A) is induced in Atlantic salmon
      (Salmo salar) following i.p. exposure to saxitoxin (STX). Salmon injected i.p.
      with sub-lethal doses of STX show a four- to eight-fold induction of hepatic
      CYP1A (as shown by ethoxyresorufin-O-deethylase activity) over controls after 96
      h. Results presented here show that the phase II XME glutathione S-transferase
      (GST) is also induced in salmon following PSP exposure. Post smolts were exposed
      to three injections of PSPs (2 micrograms STXeq/kg) over 21 days. Injection of
      both STX and PSPs extracted from a toxic strain of dinoflagellate (Alexandrium
      fundyense, CCMP 1719) resulted in induction of hepatic GST, as measured by
      activity for 1-chloro 2,4-dinitrobenzene. Such inductions indicate a potential
      role for XMEs in PSP metabolism. Possible roles for other enzymes are also
      discussed.

PMID- 11460737
TI  - Transient induction of 7-ethoxyresorufin-O-deethylase (EROD) activity by medium
      change in the rainbow trout liver cell line, RTL-W1.
AB  - Cytochrome P4501A (CYP1A) metabolizes a wide array of lipophilic xenobiotics. In
      fish liver, CYP1A is constitutively expressed at low levels, but xenobiotics can
      strongly induce CYP1A expression via a receptor-mediated pathway. While induction
      of hepatic CYP1A in teleosts by xenobiotics is well investigated, very little is
      known on the regulation of constitutive CYP1A expression and its induction by
      factors other than xenobiotics. In the present study we show that in the rainbow
      trout liver cell line, RTL-W1, CYP1A-catalyzed 7-ethoxyresorufin-O-deethylase
      (EROD) activity can be induced by a change of the culture medium, in the absence
      of xenobiotics. The increase in cellular EROD levels is of transient nature.
      Experiments with cell incubation solutions supplemented with various medium
      components indicate that photooxidized tryptophan is the agent causing the
      increase of EROD activity after medium change.

PMID- 11460738
TI  - Short-time induction of oxidative stress in hepatocytes of the European flounder
      (Platichthys flesus).
AB  - Oxidative stress induced by xenobiotic compounds has been studied using primary
      hepatocytes of juvenile European flounder (Platichthys flesus L.) caught in a low
      polluted area of the German Bight, Tiefe Rinne (Landwust et al., 1996.). Cells
      were exposed to known oxidative stressors such as hydrogen peroxide and
      benzo[a]pyrene (B[a]p) in various concentrations (50 and 100 microM) up to 6
      days. Cell mortality was determined using fluorescent ethidium homodimer-1 and
      calcein AM. Oxidative stress response was measured by image analysis using
      dihydrorhodamine 123, which is converted to fluorescent rhodamine 123 in the
      presence of intracellular ROS. Oxyradical formation was initiated already after 2
      h of exposure to low concentrations of B[a]p and hydrogen peroxide. Probably due
      to a membrane stabilising effect of the serum factors the addition of fetal
      bovine serum to the culture medium had a protecting influence on the hepatocytes
      and resulted in (1) an increased cell viability and (2) reduced formation of
      intracellular ROS during exposure. In conclusion, the assay is a sensitive tool
      for testing the potential of various xenobiotics to induce oxidative stress in
      living hepatocytes.

PMID- 11460739
TI  - Levels of cellular glutathione and metallothionein affect the toxicity of
      oxidative stressors in an established carp cell line.
AB  - The comparative toxicity of a variety of oxidative stressors was studied in the
      epithelioma papulosum cyprini line from carp using the neutral red cytotoxicity
      assay. LC50's decreased in the order t-butylhydroperoxide > hydrogen peroxide >
      diquat > paraquat. The cytotoxicity of hydrogen peroxide was significantly
      reduced when the cells were grown in L-15 medium rather than MEM and this could
      be attributed to elevated cellular glutathione and metallothionein levels and
      higher activities of GSH-dependent detoxification systems. The protective effect
      of metallothionein in radical scavenging was demonstrated by decreased toxicity
      of the redox-cycling toxicants, diquat and menadione after metallothionein levels
      had been pre-induced by Cd-exposure. This study demonstrates the relationship
      between toxic effects of oxidative stressors and expression of detoxification
      systems in fish.

PMID- 11460740
TI  - Effects of estrogen on the stress response in CuSO4-exposed PLHC-1 cells.
AB  - As part of an effort to validate the use of heat shock proteins (hsp) as a
      biomarker of adverse effect, we investigated the impact of estrogen (E2), the
      hormone responsible for vitellogenisis in fish, on the induction of hsp 60 and
      70. PLHC-1 (Pociliopsis lucida hepatoma cell line) cells were cultured under
      standard conditions and treated with either 16 ppm copper; a known inducer of hsp
      60 and 70, 1 microM estradiol, a combination of copper and estradiol, or media
      alone. Copper induced both hsp 60 and 70 two fold, while E2 alone had no effect.
      The combination of the copper and E2 inhibited the hsp 70 response, indicated by
      a 51% decrease in cellular hsp 70 compared to the copper treatment alone. In
      contrast, the expression of hsp 60 in the cells exposed to the copper-estradiol
      mixture was not significantly different than that in the copper-exposed cells.
      The results suggest that the use of hsp 70 induction in fish liver as a biomarker
      of effect may be limited by the gender and sexual maturity of the fish.

PMID- 11460741
TI  - Towards molecular understanding of species differences in dioxin sensitivity:
      initial characterization of Ah receptor cDNAs in birds and an amphibian.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated
      aromatic hydrocarbons (PHAHs) are highly toxic to most vertebrate animals, but
      there are dramatic species differences in sensitivity, both within and among
      vertebrate classes. For example, studies in cultured avian hepatocytes have
      revealed differential sensitivity of birds to PHAHs [Kennedy et al. (1996).
      Toxicol. Appl. Pharmacol., 141, 214-230]. Differences in the characteristics or
      expression of the aryl hydrocarbon receptor (AHR) could contribute to these
      species differences in PHAH responsiveness. To investigate the molecular
      mechanism of differential PHAH sensitivity, we have begun to characterize the AHR
      in white leghorn chicken (Gallus gallus), Pekin duck (Anas platyrhynchos), and
      common tern (Sterna hirundo), as well as an amphibian, mudpuppy (Necturus
      maculosus). Partial AHR cDNAs encompassing the helix-loop-helix and PAS domains
      were cloned and sequenced. Comparison of amino acid sequences in this region
      indicated a high degree of sequence conservation among the bird species (97%
      amino acid identity). The percent identity between bird sequences and either
      mouse or mudpuppy was lower (79%); the mudpuppy AHR was 74% identical to the
      mouse AHR. Phylogenetic analysis of these and other AHR amino acid sequences
      showed that the bird and mudpuppy AHRs were more closely related to mammalian and
      fish AHR1 forms than to fish AHR2. Future studies include the in vitro expression
      and functional characterization of AHRs from these and other non-mammalian
      vertebrates.

PMID- 11460742
TI  - Relation between responses in the neutral red retention test and the comet assay
      and life history parameters of Daphnia magna.
AB  - Responses of the neutral red retention (NRR) assay as test for lysosomal
      stability and the comet assay as test for DNA integrity were measured in the
      water flea, Daphnia magna, and compared with mortality and effects on population
      growth rate during short- or long-term exposure to seven different toxicants. The
      NRR test and the comet assay were performed with fresh preparations of pieces of
      tissue from the digestive tract or with cell preparations from whole daphnias.
      Five toxicants caused responses of the NRR test or the comet assay after short
      term exposure at concentrations below the acute toxicity level. Preliminary
      results of long-term exposure experiments suggest that these biomarker responses
      can be related to chronic effects on survival and/or reproduction of D. magna.
      This type of research should provide the basis for future use of the NRR test and
      the comet assay as early warning biomarkers for effects of toxicants on Daphnia
      populations.

PMID- 11460743
TI  - Skin biopsy of Mediterranean cetaceans for the investigation of interspecies
      susceptibility to xenobiotic contaminants.
AB  - Various studies on Mediterranean cetaceans have revealed bioaccumulation of
      contaminants such as organochlorines (OCs) and heavy metals. The susceptibility
      of these animals to organic pollutants and the relationship between
      bioaccumulation and population decline (as in the case of Delphinus delphis) are
      unexplored fields. In this study, we used a non-destructive approach (skin
      biopsy) to explore OC bioaccumulation processes and mixed-function oxidase
      activity (BPMO) in four species of cetaceans: striped dolphin (Stenella
      coeruleoalba), bottlenose dolphin (Tursiops truncatus), common dolphin (D.
      delphis) and fin whale (Balaenoptera physalus). Significant differences in BPMO
      induction and OC levels were found between odontocetes and mysticetes, the former
      having mixed-function oxidase activities four times higher than the latter,
      binding with levels of OCs one order of magnitude higher in odontocetes. A
      significant correlation (P < 0.05) between BPMO activities and OC levels was
      found in B. physalus. In an ongoing project, fibroblast cultures have been used
      as an alternative in vitro method of evaluating interspecies susceptibility to
      contaminants such as OCs and polycyclic aromatic hydrocarbons (PAHs). These
      results suggest that cetacean skin biopsies are a powerful non-invasive tool for
      assessing ecotoxicological risk to Mediterranean marine mammals species.

PMID- 11460744
TI  - Skin biopsies for cell cultures from Mediterranean free-ranging cetaceans.
AB  - The aim of this study was to develop a useful method for obtaining viable tissue
      samples for establishing cell cultures from skin biopsies of free-ranging
      cetaceans. The skin biopsies were performed by two methods: dart from an air gun
      and dart from a crossbow. The dart tip was modified to collect tissue. The tissue
      was kept in tissue culture medium at ambient temperature, then processed within
      24 h. Many modifications in culture technique, with respect to conventional
      culture methods for human fibroblasts, were made. The cultures thus obtained can
      be used for many purposes, including genetic and toxicological studies. In
      toxicology they are an alternative in vitro system for studying threatened
      animals such as marine mammals. In particular, fibroblasts can be used to test
      the vulnerability of cetaceans and pinnipeds to different environmental
      contaminants such as organochlorine compounds, heavy metals and polycyclic
      aromatic hydrocarbons.

PMID- 11460745
TI  - From sediment bioassay to fish biomarker--connecting the dots using simple
      trophic relationships.
AB  - Two common problems in applying and interpreting invertebrate bioassays and fish
      biomarkers in sediment toxicology are the wide gap between significant effects
      concentrations determined by these two approaches, and a general lack of
      ecological context. We have devised an exposure system that is able to reconcile
      much of the disparity between invertebrate bioassay and fish biomarker results by
      incorporating realistic ecological processes based on deposit feeding and
      predator-prey interactions. This system relates the disturbance of interest
      (sediment contamination) to biologically meaningful effects in a resource of
      interest (marine flatfish) via a realistic contaminant vector (a deposit-feeding
      polychaete worm). In this pilot study, polychaetes (Armandia brevis) were exposed
      for 28 days to clean sediments supplemented with benzo(a)pyrene (BaP), para-para
      dichlorodiphenyldichloroethylene (pp'DDE), Aroclor 1254, or field sediments
      collected from two sites in Puget Sound, Washington, contaminated predominantly
      with polcyclic aromatic hydrocarbons (PAHs) or chlorinated compounds. Exposed
      worms were then fed live to juvenile English sole (Pleuronectes vetulus) for 10
      or 12 days. At the end of the exposure period, fish were measured for length and
      weight, sacrificed, and preserved for either routine histopathology and
      immunohistochemical analysis of cytochrome P450 1A induction, or 32P post
      labeling determination of hepatic PAH-DNA adducts. Growth of predatory flatfish
      was lower than reference in all but one of eight groups fed contaminant-exposed
      polychaetes; however, statistically significant reductions in growth were only
      observed in three of these eight groups, at least in part due to low statistical
      power. Juvenile sole from all contaminant-exposed groups showed increased
      expression of CYP1A, and fish exposed to BaP-exposed worms showed clear evidence
      of hepatic PAH-DNA adducts. This method allows the concurrent evaluation of
      sediment contamination at multiple biological and ecological levels. These
      results indicate that sediments determined to be nontoxic by common invertebrate
      bioassays may have the potential to cause adverse effects at higher trophic
      levels.

PMID- 11460746
TI  - Wetland plant seedlings as indicators of near-coastal sediment quality:
      interspecific variation.
AB  - The toxicities of whole sediments collected from an urbanized Florida bayou
      estuary were determined for the epibenthic mysid, Mysidopsis bahia, and the
      infaunal amphipod, Ampelisca abdita. In addition, the phytotoxicities of the same
      sediments were evaluated using rooted macrophytes, Scirpus robustus Pursh and
      Spartina alterniflora Loisel. The results of the 24 bioassays conducted for 7-28
      days, were compared for interspecific differences. Toxicity to the benthic
      invertebrate species was predicted to be likely in all cases, based on comparison
      to effects-based sediment quality assessment guidelines. However, acute toxicity
      was uncommon and occurred at only one of the six sampling stations. In contrast,
      several sediments were either significantly phytostimulatory or phytoinhibitory
      (P < 0.05) relative to a reference estuarine sediment. The results show the
      importance of considering interspecific variation and phytoassessment in
      contaminated sediment evaluations. Phytoassessment, the focus of this research,
      provided useful information that would have been missing if only the animal test
      species were used. For this reason, the phytotoxicity data base needs to be
      increased to better evaluate the relevance of most current contaminated sediment
      evaluations for coastal areas and also to determine the realism of proposed
      numerical sediment quality assessment guidelines and criteria.

PMID- 11460747
TI  - Development of a fish in vitro cell culture model to investigate oxidative stress
      and its modulation by dietary vitamin E.
AB  - When cultured in Dulbecco's minimal essential medium the established epithelioma
      papulosum cyprini cell line from carp was found to be vitamin E-deficient due to
      the very low level of vitamin E in the medium and the foetal calf serum used as
      supplement. The toxicity of oxidative stressors to this cell line was evaluated
      by means of the neutral red cytotoxicity assay and it was found that an organic
      hydroperoxide, t-butylhydroperoxide was extremely cytotoxic and that the redox
      cycling agents diquat and menadione were less toxic. When grown under vitamin E
      supplementation (25 microM), the toxicity of these chemicals was reduced by at
      least an order of magnitude in concentration demonstrating the protective effect
      of vitamin E. These data show the importance of vitamin E status for
      interpretation of in vitro and in vivo data and that this in vitro system is
      useful for mechanistic studies.

PMID- 11460748
TI  - DNA strand breaks (comet assay) and embryo development effects in grass shrimp
      (Palaemonetes pugio) embryos after exposure to genotoxicants.
AB  - Grass shrimp embryos develop in egg sacs (stages 1-10) attached to the female for
      14-20 days after which they 'hatch' from the egg sacs into a swimming zoea stage
      (stage 11). Until they emerge from the egg sacs, embryos depend on lipids and
      lipovitellin stored within the egg. The percent of embryos which hatch after
      exposure to toxicants relative to controls was the basis of an embryo development
      assay. Exposure of embryos to chromium(III) chloride, sodium chromate, mercuric
      chloride, and 2-methyl-1,2-naphthoquinone (MNQ) resulted in a reduced hatching
      rate. In addition to effects on embryo development, DNA strand damage tests were
      carried out on contaminant-exposed embryos, using the single-cell electrophoresis
      method often referred to as comet assay. Development of stage 4 embryos was more
      affected by MNQ exposure than stage 7 embryos. The hatching rates of stages 4 and
      7 embryos exposed to MNQ (172 micrograms/l) were 0 and 90%, respectively. DNA
      strand damage, measured as DNA tail moments, were 3.4 and 4.4, respectively.
      Thus, exposure of an early embryo stage to MNQ prevented full embryo development
      while development of later embryo stages was not affected. It may be that the DNA
      repair systems are more efficient in later embryo stages than in early stages and
      thus DNA damaged in the early stages affects development.

PMID- 11460749
TI  - Effect of pollution on genetic diversity in the bay mussel Mytilus
      galloprovincialis and the acorn barnacle Balanus glandula.
AB  - To test if environmental contamination acts as a selection force affecting
      genetic diversity at the population level, two intertidal invertebrate species,
      Mytilus galloprovincialis and Balanus glandula, were collected from seven
      different bay sites in southern California. Collections were made at three
      relatively pristine 'clean' sites and four 'impacted' sites exposed to heavy
      industrial or boating activity, and which had previously been identified as
      having measurable levels of pollution. Genetic diversity at each site was
      assessed by comparing fragment polymorphisms generated from genomic DNA by
      randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). All
      populations retained a large amount of genetic diversity and were genetically
      similar to each other. However, several different measures of diversity indicated
      that, for most primers, the populations of both species from impacted sites had
      lower genetic diversity compared to those populations from clean sites.
      Individuals at impacted sites were more likely to share the same haplotypes than
      were those from clean sites. Few bands seen in the clean sites were absent from
      the impacted sites or vice versa, but a number of bands in the clean site
      populations were significantly less common in the impacted populations, while a
      few bands uncommon in clean site populations were more common at impacted sites.
      Together, these results suggest that pollution at the impacted sites may reduce
      genetic diversity among the resident invertebrate populations.

PMID- 11460750
TI  - Genotoxic, cytotoxic and developmental effects of tributyltin oxide (TBTO): an
      integrated approach to the evaluation of the relative sensitivities of two marine
      species.
AB  - Adopting an integrated approach the potential genotoxic, cytotoxic and
      developmental effects of tributyltin oxide (TBTO), a known endocrine-disrupting
      agent for neogastropods, have been evaluated in two ecologically relevant
      invertebrates: Mytilus edulis (blue mussel) and Platynereis dumerilli (rag worm).
      Following determination of the maximum tolerated dose (MTD) in terms of
      developmental and survival effects, the embryo-larval stages of these organisms
      were exposed to a range of concentrations of TBTO, and analysed for cytotoxic
      (proliferation rate index) and genotoxic (sister chromatid exchanges and
      chromosomal aberrations) effects. The study suggested that: (1) TBTO is both
      toxic and genotoxic to embryo-larval stages of both species; (2) at comparable
      concentrations, for developmental and genotoxic effects, P. dumerilii (non-target
      species) is more sensitive compared to M. edulis (target species); and (3)
      genotoxic effects are more closely tied with the development and survival of the
      organisms. The study emphasises the need of the evaluation of genotoxic potential
      of other endocrine-disrupting agents in different taxonomic groups.

PMID- 11460751
TI  - Increased potential for NAD(P)H-dependent reactive oxygen species production of
      hepatic subcellular fractions of fish species with in vivo exposure to
      contaminants.
AB  - The present study investigated the proposed involvement of contaminant-stimulated
      reactive oxygen species (ROS) production in disease processes in fish. NAD(P)H
      dependent ROS production of subcellular fractions was determined by the iron/EDTA
      mediated oxidation of 2-keto-4-methiolbutyric acid. Hepatic cytosolic NADPH
      dependent and microsomal NAD(P)H-dependent ROS production were increased 51-160%
      (P < 0.05) in rainbow trout (Oncorhynchus mykiss) 15 weeks after a single i.p.
      injection of polychlorobiphenyl (PCB) (100 mg Clophen A50 kg-1 wet wt.). Hepatic
      microsomal NADH-dependent ROS production was 114% higher in perch (Perca
      fluviatilis) from PCB-contaminated Lake Jarnsjon compared to clean Lake Vanern,
      Sweden. Hepatic mitochondrial NADH-dependent, cytosolic NADH-dependent and
      microsomal NADPH-dependent ROS production were variously elevated up to 160% in
      flounder (Platichthys flesus) at various sites along two pollution transects near
      to the ports of Rotterdam and Amsterdam, Netherlands. Overall the data indicate
      increased potential for ROS production in liver of fish exposed to field
      pollution, and support the hypothesis of oxidative stress as a mechanism of
      contaminant-mediated disease in fish.

PMID- 11460752
TI  - 32P-postlabelling analysis of DNA adducts and EROD induction as biomarkers of
      genotoxin exposure in dab (Limanda limanda) from British coastal waters.
AB  - Dab (Limanda limanda) were sampled from a number of polluted and unpolluted areas
      in British coastal waters. The 32P-postlabelling assay was used to analyse the
      level of aromatic/hydrophobic DNA adducts in pooled samples of liver tissue. The
      mean levels of DNA adducts detected from areas known to receive anthropogenic
      pollutants ranged from 4.0 to 26.8 adducts per 10(8) nucleotides, with all sites
      containing samples displaying DNA adduct profiles consisting of diagonal
      radioactive zones. In contrast no DNA adducts were detectable in samples from an
      unpolluted reference site. The ranking of polluted sites based on DNA adduct
      levels did not correspond with the ranking of sites based on sediment associated
      polycyclic aromatic hydrocarbon levels, highlighting the problem of linking the
      presence of contamination with detectable biological responses. No correlation
      could be found in this study between EROD activity and the level of DNA adducts.

PMID- 11460753
TI  - DNA adducts in hematopoietic tissues and blood of the mummichog (Fundulus
      heteroclitus) from a creosote-contaminated site in the Elizabeth River, Virginia.
AB  - Hydrophobic DNA adducts were examined in liver, anterior kidney, spleen, and
      blood of tumor-prone mummichog (Fundulus heterclitus) from the creosote
      contaminated Atlantic Wood (AW) site (Elizabeth River, Virginia). DNA adducts
      eluted in a diagonal radioactive zone, characteristic of polycyclic aromatic
      hydrocarbon exposure, in all examined tissues of AW fish. Mummichog demonstrated
      significantly higher levels of DNA adducts in spleen (394 +/- 109 nmol
      adducts/mol nucleotides) than in liver (201 +/- 77 nmol adducts/mol nucleotides)
      or anterior kidney (211 +/- 68 nmol adducts/mol nucleotides; P = 0.036). The
      levels of DNA adducts in the pooled blood (pool of four) were 142 nmol
      adducts/mol nucleotides. DNA adducts were not detected in the liver, anterior
      kidney, spleen and blood of fish collected from the reference site (< 2 nmol
      adducts/mol nucleotides). The high levels of DNA adducts detected in tissues of
      AW mummichog may be linked to the increased cancer incidence and
      immunosuppression in this population.

PMID- 11460754
TI  - Identification of cytochrome P450 1B-like sequences in two teleost fish species
      (scup, Stenotomus chrysops and plaice, Pleuronectes platessa) and in a cetacean
      (striped dolphin, Stenella coeruleoalba).
AB  - The cytochromes P450 (CYP) constitute a multigene family of enzymes playing a
      critical role in the oxidation of many endogenous and xenobiotic substrates. The
      CYP1 family is of particular interest in environmental toxicology because its
      members are dominant in the metabolism of polycyclic aromatic hydrocarbons
      (PAHs), polychlorinated biphenyls (PCBs) and aryl amines. Three members of the
      CYP1 family, CYP1A1, CYP1A2, and CYP1B1, have been identified in mammals. We
      report here on the identification and cloning of cytochrome P4501B-like sequences
      from two teleost fish species and a marine mammal. Sequences clustering with
      CYP1B1 in phylogenetic analysis were obtained from liver cDNA of scup (Stenotomus
      chrysops), genomic DNA of plaice (Pleuronectes platessa), and liver cDNA of
      striped dolphin (Stenella coeruleoalba).

PMID- 11460755
TI  - Interactive effects of cadmium and benzo[a]pyrene on metallothionein induction in
      mummichog (Fundulus heteroclitus).
AB  - Previous experiments demonstrated that exposure of mummichog to cadmium (Cd) in
      combination with benzo[a]pyrene (BaP) caused a higher mortality than would be
      expected from simple additive effects. Experiments are described here that
      investigated whether BaP exposure inhibits the induction of metallothionein (MT),
      a major detoxifying protein for Cd, or if reactive BaP metabolites compete with
      Cd for binding sites on MT. Fish were injected with or without BaP (18 mg/kg) in
      combination with a low (1 mg/kg) or high (3.2 mg/kg) dose of Cd, and in one
      treatment BP was dosed 4 days after Cd. The results showed a rapid induction of
      MT to 1.5 mg/g wet weight liver, 1 day after injecting the low Cd dose.
      Simultaneous BaP exposure significantly delayed the induction of MT, for both low
      and high Cd doses, and BaP temporarily lowered the induced MT concentration when
      dosed 4 days after induction by Cd. To test if binding of BaP metabolites to MT
      reduces the detoxification potential for Cd, microsomes of CYP1A-induced fish
      were incubated with MT and radiolabeled BaP. Active metabolism of BaP was
      observed by high-performance liquid chromatography analysis, but no association
      of BaP metabolites with MT was found. Neither could this be demonstrated in vivo,
      in liver MT isolated from mummichog dosed with 3H-BaP and Cd. These results
      suggest that increased toxicity of Cd in combination with BaP exposure is likely
      to be caused by inhibited MT synthesis, rather than by interference of BaP
      metabolites with Cd binding on MT.

PMID- 11460756
TI  - Cadmium and lead interactions with transcription factor IIIA from Xenopus laevis:
      a model for zinc finger protein reactions with toxic metal ions and
      metallothionein.
AB  - Zinc finger proteins comprise the largest class of eukaryotic transcription
      factors. The metal binding sites in these proteins have been proposed as
      plausible targets for exchange reactions between zinc and toxic metal ions that
      lead to the alteration of function of the proteins in gene transcription.
      According to the present work, both Cd2+ and Pb2+ displace Zn2+ from
      transcription factor IIIA (TFIIIA). Neither product binds to the internal control
      region (ICR) of the 5 S rRNA gene, the normal binding site for Zn-TFIIIA.
      Furthermore, the adduct of Zn-TFIIIA with ICR is also reactive with Cd2+ and
      Pb2+, leading to the dissociation of the DNA-protein complex. Cd-TFIIIA reacts
      with apometallothionein (apoMT) to form Cd-MT and apoTFIIIA. Similarly, Cd2+ and
      Zn2+ can be exchanged in the reaction of Cd-TFIIIA with Zn-MT. Zn-finger 3 of
      TFIIIA has also been examined to compare the reactivity of a single finger motif
      with fingers in the holoprotein. Zn-finger 3 reacts with much faster kinetics
      than the holoprotein.

PMID- 11460757
TI  - The requirements for stable metallothionein clusters examined using synthetic
      lobster domains.
AB  - Metallothioneins (MTs) are small, cysteine-rich proteins which detoxify
      xenobiotic metals such as cadmium (Cd) and mercury (Hg). In crustaceans and
      mammals they consist of two independent domains which are folded around metal
      thiolate clusters. MT clusters of different origins, exhibiting distinct, highly
      conserved cysteine positions on their sequences, show differences in metal
      cysteine coordination and reactivity. Lobster-MT, containing two Cd3 beta
      domains, is an important model for structure-function relationships among the
      clusters. The influence of (1) the position of the cysteine residues and (2)
      steric and electrostatic effects of neighboring amino acids on the folding and
      stability of MT cluster were investigated. Thus, the native lobster beta C and
      beta N domains (each having nine cysteines and binding three M2+ ions) and a
      modified domain Cd3 beta C-->N, in which the cysteines of the C-terminal domain
      were relocated to match the positions of those in the N-terminal domain, were
      chemically prepared and characterized. The synthetic native domains (Cd3 beta C
      and Cd3 beta N) were found to exhibit spectroscopic properties, metal-binding
      affinities and kinetic reactivity similar to the holo-protein. However, the
      modified Cd3 beta C-->N domain was unusually reactive and in the presence of
      Chelex, metal chelation resin, aggregated to a Cd5(beta C-->N)2 dimer, which
      exhibited unusual structure as observed by its 113Cd-nuclear magnetic resonance.
      These differences in structure and reactivity demonstrated that the requirements
      for formation of a stable Cd3S9 beta-cluster are more stringent than simply the
      sequential positions of the cysteines along the peptide chain and must include
      interactions involving neighboring, noncysteine amino acids.

PMID- 11460758
TI  - Cadmium speciation and transport in the blood of the bivalve Mytilus edulis.
AB  - Cadmium (Cd) speciation in the blood plasma of Mytilus edulis was investigated
      using the metal speciation model MINTEQA2. In the presence of inorganic ions
      alone, Cd-chloro complexes dominated the speciation (97% of total Cd), with 3% as
      Cd2+. Inclusion of a novel Cd-binding histidine-rich glycoprotein (HRG) purified
      from mussel blood plasma decreased the contribution of chloro-complexes to 11.9%,
      with 86.8% of the Cd bound to the HRG and 1.3% present as Cd2+. Cd transfer from
      the blood plasma to the kidneys in vivo was studied by injecting 109Cd (both with
      and without additional chelation) into mussels. Oxine and EDTA complexed a
      significant amount of blood-borne Cd (23.7% Cd Oxine; 57.1% CdEDTA). In the
      presence of each chelator, plasma retained significantly more Cd, although there
      was no significant difference in Cd uptake by tissues (kidney, gill-mantle, and
      remaining viscera).

PMID- 11460759
TI  - Dental caries trends in 5 to 6 year-old and 11 to 13 year-old children in two
      UNICEF designated regions: Sub-Saharan Africa, and Middle East and North Africa,
      1970-2000.
AB  - The purpose of this study was to do a systematic review of published caries
      epidemiology studies in two UNICEF defined regions, Sub-Sahara Africa, and the
      Middle-East and North Africa that contain 63 developing countries. On-line
      searches were made of articles listed in Medline using PubMed to investigate
      trends in dental caries in 5 to 6 year-old, and 11 to 13-year-old children using
      defined inclusion criteria. Of 493 listed publications, 70 fulfilled the
      inclusion criteria. The percentage caries rates and mean dmft, as well as mean
      DMFT scores, were plotted against study year. Non-significant percentage caries
      prevalence trends were downward in Sub-Saharan Africa for both 5-6 year-olds and
      11-13 year-olds while in Middle-East and North Africa caries prevalence remained
      constant over the 30-year review period in both age groups. Mean dmft scores
      significantly diminished in 5-6 year-olds during the study period (y = 200-0.1x,
      P = 0.05) in Sub-Saharan Africa but the scores remained constant in the Middle
      East and North Africa. Mean DMFT scores remained constant in 11-13 year-olds in
      both Sub-Saharan Africa and the Middle-East and North Africa. When the mean dmft
      and DMFT scores per carious mouth were calculated both age groups in Sub-Saharan
      Africa showed clear reductions, that for 11 to 13 year-olds was statistically
      significant (y = 170-0.084x, P = 0.014). In the Middle-East and North Africa the
      trends in the two age groups remained unchanged.

PMID- 11460760
TI  - [Evaluation of radiation dose and radiation risk for dental patients].
AB  - 1. The collective dental radiation dose in Israel in 1998 is 42.86 Sv. 2. The
      collective dental radiation is responsible for a mortality of about 2.14 people
      per year in Israel, and a similar number of morbidity from non-lethal cancer. 3.
      It seems that the quality of the picture in dental radiographs in Israel is not
      satisfactory, so is the dentists' level of knowledge about it. 4. Exposure to
      dental radiographs may be reduced by half if measures are taken to ensure the
      quality of the radiographs and the knowledge of dentists on the subject.

PMID- 11460761
TI  - [Splinting--a review of the literature].
AB  - Early evidence for the use of splints can be seen in ancient civilizations, but
      the concept of Splinting teeth to support and immobilize teeth, by joining
      several teeth together continues to be a topic of controversy. Splints can be
      classified based on their purpose and duration of use, the way of fabrication,
      and the location of the splinted teeth in the jaw. The biomechanical mechanism of
      splint is related to the mechanism of tooth mobility. The indications for splint
      usage in the healthy and diseased periodontium are variable, among them are:
      prevention of mobility after acute trauma, for occlusal therapy, to allow
      function, to allow periodontal repair, in case of occlusal trauma, to prevent
      teeth drifting after orthodontic treatment or when a tooth is missing. Due to the
      many disadvantages splints have, splinting should be used cautiously, specially
      in splinting teeth and implants.

PMID- 11460762
TI  - [Preliminary results of short-term follow-up after MIS screw-type implants with
      rough surface].
AB  - The present article describes the preliminary results of a short-term follow up
      retrospective study of 104 external hex, screw-type MIS implants with rough
      surface that were consecutively implanted in 34 patients. The implants were
      followed up between 1 to 3 years. 49 implants were placed in the maxilla and 55
      in the mandible. Bone regenerative procedures were carried out simultaneously in
      the time of implant placement in 21 of the implants. A total of 6 implants failed
      (5.7%) during the observation period, all in the first year after implant
      placement. Two implants failed in the same diabetic patient, and one in a heavy
      smoker. Two of the failed implants were placed together with bone regenerative
      procedures, and another one was with no initial stability at the time of implant
      placement. This short-term follow up report has shown that the success rate of
      MIS screw-type implants with rough surface is similar to the success rate
      reported for other implant systems. However, long-term follow up is needed to
      verify the long-term success MIS implant system.

PMID- 11460763
TI  - [The association between periodontal diseases and coronary artery diseases--a
      literature review].
AB  - The relation between periodontal disease and atherosclerotic cardiovascular
      disease was reported the first time at the end of the Eighties. Screening of the
      English written reported research papers revealed an increased risk of coronary
      artery disease and Cerebrovascular disease, in patients suffering from chronic
      periodontal infection. The same relation was found in patient who underwent
      multiple tooth extraction as a result of chronic advanced periodontal disease.
      These observations stress the importance of maintaining good oral hygiene and the
      prevention of chronic periodontal disease. The precise mode of influence,
      pathophysiology is still obscured, possible mechanisms were suggested. An
      indirect risk, by raising infection markers, such as fibrinogen and c-reactive
      protein. Other possibilities are by direct influence on Atherosclerotic plaque
      formation or another common cardiovascular risk factor such as smoking which
      influence both cardiovascular and periodontal diseases.

PMID- 11460765
TI  - Dentists assisting Israeli police.

PMID- 11460764
TI  - [Vertical alveolar ridge augmentation using distraction osteogenesis].
AB  - Alveolar ridge atrophy can be acquired or congenital. Alveolar ridge augmentation
      can be performed using bone grafting but a donor site morbidity is unavoidable
      and some resorption of the grafted bone occurs. Distraction osteogenesis offers
      an alternative method for bone reconstruction without donor site morbidity and
      sufficient stability of the final results. In order to place implants, vertical
      alveolar augmentation using Distraction Osteogenesis has been applied to 14
      patients aged 17 to 55 years old with edentulous alveolar ridge, 8 in the
      mandible and 6 in the maxilla. Vertical alveolar bone distraction was started by
      performing a segmental alveolar osteotomy followed by insertion of a central
      distraction device--Lead System (Endosseous alveolar distraction system,
      Leibinger). After three days of latency period, the distraction was started in a
      rate of 0.8 mm per day for 9 to 16 days as needed. The retention period for the
      new bone maturation was twice as long as the active distraction period. After
      removal of the device, 23 cylindrical threaded implants were inserted. The
      results revealed increase of the alveolar bone height with new bone formation
      that was observed radiographically and clinically at the removal of the
      distraction device. The amount of elevation was 7-13 mm. In follow-up of 6-14
      months, failure of only one implant was noted, due to inadequate transported bone
      stability. The advantages of alveolar bone distraction are: Increase of the
      alveolar bone height with new bone formation, minimal resorption of bone without
      the bone graft disadvantages. A long term follow up after the bone height
      achieved and implant anchorage should be performed in the future.

PMID- 11460766
TI  - Endpoints of arm movements to visual targets.
AB  - Reaching out for objects with an unseen arm involves using both visual and
      kinesthetic information. Neither visual nor kinesthetic information is perfect.
      Each is subject to both constant and variable errors. To evaluate how such errors
      influence performance in natural goal-directed movements, we asked subjects to
      align a real 5-cm cube, which they held in their hand but could not see, with a
      three-dimensional visual simulation of such a cube. The simulated cube was
      presented at one of four target locations at the corners of an imaginary
      tetraeder. Subjects made successive, self-paced movements between these target
      locations. They could not see anything except the simulated cube throughout the
      experiment. Initial analysis of the spatial dispersion of movement endpoints
      demonstrated that the major source of errors under these conditions was visual.
      Further analysis of the relationship between variability of the starting
      positions and endpoints showed that the errors were primarily in judging the
      endpoint, rather than the direction or amplitude of the required movement vector.
      The findings support endpoint control of human goal-directed movements.

PMID- 11460767
TI  - Hand trajectory invariance in reaching movements involving the trunk.
AB  - Movements of different body segments may be combined in different ways to achieve
      the same motor goal. How this is accomplished by the nervous system was
      investigated by having subjects make fast pointing movements with the arm in
      combination with a forward bending of the trunk that was unexpectedly blocked in
      some trials. Subjects moved their hand above the surface of a table without
      vision from an initial position near the midline of the chest to remembered
      targets placed within the reach of the arm in either the ipsi- or contralateral
      workspace. In experiment 1, subjects were instructed to make fast arm movements
      to the target without corrections whether or not the trunk was arrested. Only
      minor changes were found in the hand trajectory and velocity profile in response
      to the trunk arrest, and these changes were seen only late in the movement. In
      contrast, the patterns of the interjoint coordination substantially changed in
      response to the trunk arrest, suggesting the presence of compensatory arm-trunk
      coordination minimizing the deflections from the hand trajectory regardless of
      whether the trunk is recruited or mechanically blocked. Changes in the arm
      interjoint coordination in response to the trunk arrest could be detected
      kinematically at a minimal latency of 50 ms. This finding suggests a rapid reflex
      compensatory mechanism driven by vestibular and/or proprioceptive afferent
      signals. In experiment 2, subjects were required, as soon as they perceived the
      trunk arrest, to change the hand motion to the same direction as that of the
      trunk. Under this instruction, subjects were able to initiate corrections only
      after the hand approached or reached the final position. Thus, centrally mediated
      compensatory corrections triggered in response to the trunk arrest were likely to
      occur too late to maintain the observed invariant hand trajectory in experiment
      1. In experiment 3, subjects produced similar pointing movements, but to a target
      that moved together with the trunk. In these body-oriented pointing movements,
      the hand trajectories from trials in which the trunk was moving or arrested were
      substantially different. The same trajectories represented in a relative frame of
      reference moving with the trunk were virtually identical. We conclude that hand
      trajectory invariance can be produced in an external spatial (experiment 1) or an
      internal trunk-centered (experiment 3) frame of reference. The invariance in the
      external frame of reference is accomplished by active compensatory changes in the
      arm joint angles nullifying the influence of the trunk motion on the hand
      trajectory. We suggest that to make a transition to the internal frame of
      reference, control systems suppress this compensation. One of the hypotheses
      opened to further experimental testing is that the integration of additional
      (trunk) degrees of freedom into movement is based on afferent (proprioceptive,
      vestibular) signals stemming from the trunk motion and transmitted to the arm
      muscles.

PMID- 11460768
TI  - Cross-axis adaptation of the translational vestibulo-ocular reflex.
AB  - The adaptive plasticity of the translational vestibulo-ocular reflex (VOR) was
      investigated in rhesus monkeys after 2-h exposure to either vertical or torsional
      optic flow stimulation accompanied by lateral translation stimuli (0.5 Hz).
      Because of the inherent ambiguity in the otolith system for the detection of
      gravitoinertial accelerations, we hypothesized that cross-axis adaptation of the
      translational VOR during lateral motion would be preferentially selective for a
      torsional optic flow stimulus that would mimic a roll tilt movement. However, we
      found that both vertical and torsional adaptation was possible. Furthermore,
      there was no significant preference for whether the torsional adaptation was in
      phase or out of phase with the apparent tilt induced by the motion stimulus.
      These results suggest that, at least at 0.5 Hz, there seems to be no
      preferential, visually induced adaptive capacity of the otolith system for
      tilt/translation reinterpretation during motion. Like the rotational VOR,
      translational VOR appears to exhibit a general form of cross-axis adaptation that
      operates for different directions of optic flow stimulation.

PMID- 11460769
TI  - Coordination in childhood: modifications of visuomotor representations in 6- to
      11-year-old children.
AB  - This research investigated the development of visuomotor coordination in
      childhood, more specifically the conversion of visual information into motor
      sequences. Three groups of children (aged 6, 8 and 11 years) and a group of
      adults performed pointing movements without direct feedback from their arm
      displacements. Visual information, provided by a video camera, was disturbed by
      rotations of 0 degree, 45 degrees, 90 degrees, 135 degrees or 180 degrees. Six
      year-old children showed poor accuracy for 180 degrees rotations. These results
      suggest that the youngest children use unidirectional representations to convert
      visual information into motor sequences. At 8 years of age, children showed a
      shift from unidirectional to bidirectional representations, as reflected by
      reduced errors for 180 degrees rotations. Eleven-year-old children and adults
      showed the same type of representations, i.e., bidirectional. However, as
      reflected by their slower movement time and slower modifications in temporal
      accuracy across trials, the oldest children have not yet reached maturation in
      their adaptive process when compared to adults.

PMID- 11460770
TI  - The effect of a fatiguing exercise by the index finger on single- and multi
      finger force production tasks.
AB  - We studied the effects of fatigue, induced by a 60-s maximal isometric force
      production with the index finger, on multi-finger coordination and force
      production by the other fingers of the hand. Finger forces were measured during
      single- and multi-finger maximal voluntary force production (MVC) at two sites,
      the middle of the distal or the middle of the proximal phalanges. Two fatiguing
      exercises involving force production by the index finger were used, one at the
      distal phalanx and the other at the proximal phalanx. The MVC of the index finger
      dropped by about 33% when it was produced at the site involved in the fatiguing
      exercise. In addition, large transfer effects of fatigue were observed across
      sites of force application and across fingers. Force deficit increased under
      fatigue, especially due to a drop in the recruitment of the index finger. Under
      fatigue, the index finger was less enslaved during force production by other
      fingers. During multi-finger tasks, the percentage of total force produced by the
      index finger was significantly reduced after the fatiguing exercise. The
      principle of minimization of secondary moments was violated under fatigue. We
      suggest that the most impaired (fatigued) finger shows less interaction with
      other fingers or, in other words, is being progressively removed from the multi
      finger synergy. Some of the observed changes in finger coordination suggest
      effects of fatigue at a central (neural) level.

PMID- 11460771
TI  - Inhibition of return in averaging saccades.
AB  - When subjects make a quick saccade to one of two stimuli that are presented
      closely and simultaneously in the peripheral visual field, their eyes often land
      at a midpoint somewhere between the stimuli (saccadic averaging). The present
      study investigates whether and how the inhibition-of-return phenomenon (IOR;
      slower reaction times for the previously attended locations) influences spatial
      parameters of averaging saccades. Subjects were asked to quickly move their eyes
      toward one of two stimuli that were presented closely and simultaneously. Most
      subjects showed a clear tendency toward saccadic averaging. When an uninformative
      cue was presented 600 ms before the two stimuli (long enough to produce IOR),
      saccadic averaging still occurred but the saccade landing locations were biased
      toward the uncued location. Thus, the present study demonstrates that the
      mechanisms responsible for IOR affect the metrics of averaging saccades and
      suggests that IOR can be manifested not only in the temporal aspects but also in
      the spatial aspects of oculomotor behaviors.

PMID- 11460772
TI  - Plastic response of the retrospleniocollicular connection after removal of
      retinal inputs in neonatal rats. An anterograde tracing study.
AB  - The effects of neonatal enucleation on the final adult pattern of
      retrospleniocollicular connection in the rat was studied using the anterograde
      tracer biotindextranamine 10,000 (BDA) iontophoretically injected in different
      anteroposterior locations of the retrosplenial cortex. Retrosplenial afferents
      are normally distributed in all collicular layers beneath the stratum griseum
      superficiale (SGS) throughout almost the entire rostrocaudal and lateromedial
      collicular axes. Neonatal enucleation caused an invasion of lower SGS by abundant
      retrosplenial afferents, whose distribution remained unaltered in intermediate
      and deep collicular layers. Axons entering the deafferented SGS showed variable
      morphologies and arborization patterns. Some of them ran lateromedially close to
      the SGS-stratum opticum (-SO) limit, giving rise to many collaterals which
      invaded the lower part of the SGS; whereas others formed narrow terminal arbors,
      mostly branching in the SO. In the intermediate layers, synaptic profiles were
      mainly found close to the borders of acetylcholinesterase (AChE) patches in both
      control and enucleated animals, indicating that neonatal enucleation does not
      alter the final pattern of retrospleniocollicular afferents to these collicular
      regions. The results presented here demonstrate that neonatal enucleation leads
      to the development of an aberrant projection from the retrosplenial cortex to the
      deafferented superficial layers of the superior colliculus. These results provide
      new information regarding the reorganization of connections subsequent to
      neonatal enucleation and suggest that, in enucleated animals, nonvisual
      multisensorial information could be relayed to central circuits which in intact
      animals belong to the visual system.

PMID- 11460773
TI  - The gap effect for eye and hand movements in double-step pointing.
AB  - The existence of a temporal gap between the offset of a fixation target and the
      onset of a peripheral target generally reduces the saccadic and manual reaction
      time in response to the peripheral target. Using a double-step paradigm, the
      present experiment investigated whether a temporal gap between the extinction of
      the first target and the presentation of the second target can help in reducing
      the time to trigger the corrective eye movements and to correct the arm
      trajectory towards the final target position. A gap was introduced between the
      presentation of the initial target and a new unexpected goal-target during the
      movement. The results replicated the gap effect for the corrective saccade to the
      second target, but revealed an opposite effect for the correction of the reaching
      movements as the arm correction occurred later in the Gap than in the No-Gap
      conditions. These results suggest that the information available for the arm
      motor system to correct the trajectory in relation to the second target was
      different in the Gap and No-Gap conditions. In the No-Gap condition, the
      correction of reaching movements would be based on retinal errors between the
      first and the second targets whereas, in the Gap condition, the correction would
      be based on information derived from the corrective saccade-related signals to
      the second target.

PMID- 11460774
TI  - Conditions for interference versus facilitation during sequential sensorimotor
      adaptation.
AB  - We investigated how sensorimotor adaptation acquired during one experimental
      session influenced the adaptation in a subsequent session. The subjects' task was
      to track a visual target using a joystick-controlled cursor, while the
      relationship between joystick and cursor position was manipulated to introduce a
      sensorimotor discordance. Each subject participated in two sessions, separated by
      a pause of 2 min to 1 month duration. We found that adaptation was achieved
      within minutes, and persisted in the memory for at least a month, with only a
      small decay (experiment A). When the discordances administered in the two
      sessions were in mutual conflict, we found evidence for task interference
      (experiment B). However, when the discordances were independent, we found
      facilitation rather than interference (experiment C); the latter finding could
      not be explained by the use of an "easier" discordance in the second session
      (experiment D). We conclude that interference is due to an incompatibility
      between task requirements, and not to a competition of tasks for short-term
      memory. We further conclude that the ability to adapt to a sensorimotor
      discordance can be improved by practicing with an unrelated discordance.

PMID- 11460775
TI  - An investigation into mechanisms of reflex reinforcement by the Jendrassik
      manoeuvre.
AB  - Tendon jerk and H-reflexes are both potentiated by the Jendrassik manoeuvre, but
      the mechanism of potentiation remains uncertain. We investigated several
      possibilities in human subjects. Evidence for fusimotor activation during the
      Jendrassik manoeuvre was sought by recording the tendon jerk reflex as surface
      EMG in triceps surae after the muscles had been conditioned to leave their
      spindles in a slack, insensitive state. Interposing a Jendrassik manoeuvre
      between conditioning and the test reflex should have increased reflex amplitude
      by restoring spindle sensitivity, but this was not the case. In humans, a close
      synergist of the triceps surae is the quadriceps. A possible presynaptic
      disinhibitory mechanism was investigated by testing the effect of a Jendrassik
      manoeuvre on facilitation of the soleus H-reflex produced by a quadriceps
      afferent volley. The Jendrassik manoeuvre failed to increase facilitation,
      contrary to what would be expected if it reduced the level of tonic presynaptic
      inhibition; the assumption being that the inhibition acts on both homonymous and
      synergist afferent terminals. The Jendrassik manoeuvre did not increase the level
      of ongoing EMG in the soleus during a weak voluntary contraction, indicating that
      it does not operate by direct facilitation of motoneurones. There was found to be
      less potentiation of soleus tendon jerk and H-reflexes by the Jendrassik
      manoeuvre under conditions when spindles in the soleus were likely to have a high
      resting discharge rate. A remaining possibility is discussed: that the Jendrassik
      manoeuvre operates by modulation of oligosynaptic pathways that may contribute to
      the largely monosynaptic reflex response. These experiments demonstrate, with
      new, more sensitive methods than previously used, that neither is the fusimotor
      system involved in reinforcement nor are direct excitatory or presynaptic
      disinhibitory effects on motoneurones. While this confirms the previously
      prevailing view, none of the lingering uncertainties associated with the methods
      used now remains.

PMID- 11460776
TI  - Comparison between hypothermia and glutamate antagonism treatments on the
      immediate outcome of perinatal asphyxia.
AB  - This study investigated the influence of temperature or glutamate antagonism on
      the immediate outcome of perinatal asphyxia. Perinatal asphyxia was produced by
      water immersion of fetus-containing uterus horns removed by cesarean section from
      ready to deliver rats. The uterus horns were kept in a water bath for different
      time periods, before the pups were delivered and stimulated to breathe. After
      delivery, the pups were assessed for behavior and for systemic glutamate,
      aspartate, lactate and pyruvate levels measured with in vivo microdialysis, or ex
      vivo for energy-rich phosphates, including adenosine triphosphate (ATP), in
      brain, heart and kidney. In a series of experiments, asphyxia was initiated in a
      water bath at 37 degrees C, before the pup-containing uterus horns were moved for
      different time intervals to a 15 degrees C bath. In another series of
      experiments, the mothers were treated with N-methyl-D-aspartate (NMDA)
      antagonist, dizocilpine (MK-801), or alpha-amino-3-hydroxy-methylisoxazole-4
      propionic acid (AMPA) antagonist,2,3-dihydroxy-6-nitro-7-sulfamoyl benzo(f)
      quinoxalin NBQX) 1 h before hysterectomy and asphyxia at 37 degrees C. The rate
      of survival rapidly decreased following exposure to more than 16 min of asphyxia,
      and no survival could be observed after 22 min of asphyxia. An LD50 was estimated
      to occur at approximately 19 min of asphyxia. The outcome was paralleled by a
      decrease in ATP in kidney, followed by a decrease in heart and brain. A maximal
      decrease in ATP was observed after 20 min of asphyxia in all tissues. Systemic
      microdialysis revealed that glutamate, aspartate and pyruvate levels were
      increased with a peak after 5 min of asphyxia. In contrast, lactate levels
      increased along with the length of the insult. Survival was increased when the
      pup-containing uterus horns were moved from a 37 degrees C to a 15 degrees C
      bath, at 15 min of asphyxia (the LD50 was thus increased to 30 min). If the shift
      occurred at 10 or 5 min of asphyxia, the LD50 increased to 80 or 110 min,
      respectively. The effect of glutamate antagonism was minor compared to
      hypothermia; the best effect (an increase in the LD50 to approximately 22 min)
      was observed after combining AMPA and NMDA antagonists.

PMID- 11460777
TI  - Focal cerebral ischemia induces increased myelin basic protein and growth
      associated protein-43 gene transcription in peri-infarct areas in the rat brain.
AB  - Although oligodendrocytes are vulnerable to focal cerebral ischemia,
      remyelination of denuded or regenerating axons in the peri-infarct area has been
      observed in the central nervous system. We studied the expression of myelin basic
      protein (MBP), a major component of central nervous system myelin, in peri
      infarct areas in adult rat brain after transient middle cerebral artery occlusion
      (MCAO) and correlated it to the expression of the growth-associated protein-43
      (GAP-43), a marker for axonal regeneration and sprouting, using non-radioactive
      in situ hybridization techniques. Within the infarct, MBP messenger RNA (mRNA)
      had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin
      oligodendrocyte glycoprotein (MOG) immunohistochemistry, appeared structurally
      intact until day 3. Peri-infarct oligodendrocytes increased their expression of
      MBP mRNA from 24 h to maximal levels at day 7, corresponding to the appearance of
      process-bearing MBP and occasional MOG-immunoreactive oligodendrocytes in
      parallel sections. Quantitative analysis revealed significant increases in the
      density of oligodendrocytes (up to 7.6-fold) and in the level of MBP mRNA
      expressed by individual cells. Parallel sections showed that increased expression
      of GAP-43 mRNA in neurons was concomitant to MBP mRNA upregulation in
      oligodendrocytes. While the mechanisms regulating oligodendrocyte survival and
      myelination signals are not clear at this point, axonal sprouting could
      putatively serve as a stimulus for the upregulation of oligodendrocyte cell
      numbers, differentiation state, and/or active myelination in the peri-infarct
      areas.

PMID- 11460778
TI  - Ocular pursuit of predicted motion trajectories.
AB  - The initiation and maintenance of slow eye movements (SEMs) usually depend on the
      perception of a moving stimulus. However, the endogenous representation of
      predictable target motion can be sufficient to initiate and maintain brief
      episodes of SEM even when the stimulus is not present. In this note, we show that
      expectancies generated by predictable stimulus motion trajectories can also
      produce smooth deceleration, reversal of direction, and subsequent acceleration
      in these movements, and explore the limits of the predictive component of the SEM
      control system quantitatively.

PMID- 11460779
TI  - Changes in the colocalization of glutamate ionotropic receptor subunits in the
      human epileptic temporal lobe cortex.
AB  - Double-labeling immunocytochemical techniques and confocal microscopy were used
      to quantify possible differences in the degree of colocalization of glutamate
      ionotropic receptor subunits between non-spiking and spiking neocortex removed
      from temporal lobe epileptic patients. Spiking neocortex was characterized by
      laminar-specific changes in the number of cells immunoreactive for NMDAR1,
      GluR2/3 and GluR5/6/7 subunits, as well as the percentage of cells which
      colocalized various combinations of these receptors. These changes may lead to
      profound modifications in the functioning of excitatory synaptic circuits in
      spiking cortex.

PMID- 11460780
TI  - Transferring insect skills for survival.

PMID- 11460781
TI  - Reuse of single-use devices.

PMID- 11460782
TI  - A collaborative program for cardiovascular patient follow-up.
AB  - Transitions from one health care system to another are common, but they can
      affect coordination of care and measurement of patient outcomes. In this project,
      a community hospital and a tertiary center collaborated to obtain follow-up
      information on patients 30 days after they underwent cardiac catheterization and
      revascularization. Results show that patients experienced similar physical and
      emotional concerns regardless of diagnosis or procedure. Although the intent was
      to gather information, nurses also provided education and arranged services for
      patients. This project has implications for the development of collaborative
      interventions to improve care for patients after undergoing coronary procedures.

PMID- 11460783
TI  - A practical approach to achieving bloodless surgery.
AB  - The term bloodless surgery refers to the practice of performing surgical
      procedures without the use of allogenic blood and avoiding the use of stored
      blood, including autologous blood, entirely. This article reviews the scientific
      and clinical literature regarding bloodless surgery and describes the application
      of a full-service, bloodless program within a community hospital.

PMID- 11460784
TI  - Dental surgery in pediatric patients with spina bifida and latex allergy.
AB  - Dental rehabilitation is a common outpatient pediatric surgical procedure. It
      requires the dentist to restore or extract the teeth of children with severe
      tooth decay or poor dental hygiene. Medical, physical, or emotional problems can
      make safe treatment in an outpatient setting impossible. These children require
      sedation or anesthesia for the dentist to gain access to their oral cavities.
      This article discusses caring for pediatric patients with spina bifida and latex
      allergy undergoing dental rehabilitation. Perioperative nurses must act as
      patient advocates in providing a latex-safe environment and also ensure quality
      care.

PMID- 11460785
TI  - Use of x-ray in the presence of an incorrect needle count.

PMID- 11460786
TI  - Ethnography as a qualitative research method.

PMID- 11460787
TI  - Laws pertaining to third-party reimbursement of RN first assistants.

PMID- 11460789
TI  - [A decade of the RAPD method: possibilities and limitations for plant genetics
      relationship studies].
AB  - The RAPD method appeared a decade ago as an alternative in genetic relationship
      studies. The technique generates polymorphic band patterns, produced by PCR using
      arbitrary DNA sequence primers. If total DNA is used, RAPD yields abundant
      information about the analyzed genome in a rapid and inexpensive way. This
      information may be used in various types of plant genetic studies, such as hybrid
      detection, intra and interspecific genetic variation, genetic identity
      establishment, somaclonal variation analysis and, when combined with other
      methods, it helps in the elaboration of genetic maps. However, there are some
      requisites for its correct application. A strict control of working conditions is
      demanded. Furthermore, due to the anonymous character of polymorphic bands and
      the difficulties for establishing homologies, it is also recommended to confine
      RAPD uses to the specific or infra specific levels. Comparisons based on genetic
      distance calculations are accepted provided they do not require parsimony
      analysis methods.

PMID- 11460790
TI  - [A viral infection in the neck glandula of larvae of Dione junio (Lepidoptera:
      Nymphalidae)].
AB  - Lepidopteran larvae may be attacked by different viruses, many of which belong to
      the Baculoviridae family. Whilst studying the ultrastructure of the neck gland in
      Dione junio larvae we found that in later instars the larvae showed symptoms of
      attack by two types of virus. The glands were prepared for optical and electron
      microscopy using sodium cacodylate buffer and standard procedures (0.1M, pH 7.2).
      The neck gland is composed of two oval internal sacks which communicate with the
      exterior via an extracellular channel. Each sack contains, in its external
      region, cells with large, irregular nuclei and a dense cytoplasm containing
      numerous small mitochondria. In infected larvae, the tissues are damaged and the
      nuclear polyhedrosis virus can be observed in several of the nuclei. In the
      cytoplasm another "rickettsia type" virus, may be observed. The pathogenic
      viruses present in D. junio larvae could be studied as potential biological
      controls of this pest.

PMID- 11460791
TI  - [Effect of arterial proteoglycans on in vitro oxidation of LDL isolated from
      hypercholesterolemic patients].
AB  - The interaction of LDL with extracellular matrix proteoglycan apparently
      contribute to the accumulation of apo B-lipoproteins in atherogenesis. Retention
      of LDL by intima proteoglycans appears to increase the residence time needed for
      their structural, hydrolytic and oxidative modification. If the rate of LDL entry
      exceeds the tissue capacity to eliminate the modified products, this process may
      contribute to atherogenesis. In this study we explored whether alterations of LDL
      induced by human arterial CSPG alter the lipoprotein susceptibility to copper
      catalyzed oxidation. Human LDL was complexed with human arterial CSPG and
      dissociated by raising the ionic strength. The CSPG-treated LDL was subjected to
      oxidation by micromolar amounts of copper. This treatment increased LDL
      susceptibility to oxidation 8 times, as indicated by formation rates of
      thiobarbituric acid-reacting substances (TBARS). Furthermore, the
      hypercholesterolemic patients show LDL with significantly higher affinity for
      arterial proteoglycans than LDL from controls.

PMID- 11460792
TI  - [Production of Kluyveromices fragilis biomass in deproteinized milk whey].
AB  - The milk whey from a mature cheese factory deproteinised by acid thermic
      coagulation (pH 4.5 and 90 degrees C), provides a good culture media for the
      production of Kluyveromices fragilis biomass. The optimal experimental conditions
      for the maximal production of biomass were established by using fermenters with
      different capacity and design. For lactose concentration of 15 g/l, pH 4.5, 30
      degrees C and aireation between 0.25 and 1 VVM, the duplication time was below
      two hours and 98% of the lactose was consumed. The obtained yield in dried weight
      was between 36 and 49% (g biomass/g lactose). The biomass (without broken cell)
      contain 46% protein on dry base and showed an "in vitro" digestibility of 65%.
      The organic mass decreased 80% after 12 hour of fermentation. This process
      eliminates a polluting agent and simultaneously, produces a biomass that could
      have industrial use as a protein complement in feeds.

PMID- 11460793
TI  - Utilization of bee (Apis mellifera) honey for vinegar production at laboratory
      scale.
AB  - Vinegar was obtained from bee (Apis mellifera) honey. The wort was prepared by
      diluting honey in distilled water to 21% total solids and by adding ammonium
      sulfate and ammonium phosphate. Saccharomyces cerevisiae was inoculated to the
      wort (4 g/L). Ethanol production was carried out at room temperature during 84
      hours. In this study, 1 Kg of honey yielded about 5 L of wine, containing 8%
      alcohol (v/v), from a wort with 17.11% total sugars (w/v). The efficiency of the
      alcoholic fermentation was 81.34%. The acetic fermentation with an inoculum of
      mixed acetic microorganisms was performed by quick process in a 15 L vertical
      fermenter. This resulted in a vinegar containing up to 9% of acetic acid (w/v)
      and about 1% of alcohol (v/v). The acetic fermentation yielded between 91.24 and
      97.21%. Approximately 5 L of honey vinegar with 9% acetic acid (w/v) were
      obtained from 1 Kg of bee honey. All attributes of honey vinegar showed
      acceptability index over 70%: 95.37% for appearance, 94.81% for color, 79.07% for
      odor and 75.56% for flavor, indicating it would show good consumer acceptability.

PMID- 11460794
TI  - [Behavior of some anthropometric, clinical and biochemical variables in boys and
      girls 8 to 12 years of age from the longitudinal study of the metropolitan area].
AB  - A longitudinal principal components analysis was used to summarize trends or
      intraindividual changes in weight, height, blood pressure, serum cholesterol and
      triglycerides in 32 boys and 28 girls from the Caracas Longitudinal Study (1976
      1982), who started follow-up at age 8. A first component was identified for each
      variable, it represents a measure of position across the whole age period, a
      "canalization pattern". This component accounted for most of the total variance.
      The second component represents an unidirectional change in relative position of
      the values of the variable, a "decanalization pattern", and a third pattern
      summarized deviations around a position level: "recanalization pattern". The
      results from the correlation analyses between the components indicate a positive
      and significant association between the identified trends. These patterns allow
      predictability of "high and low risk" factors of non-communicable chronic
      diseases.

PMID- 11460795
TI  - [Adiposity distribution in adolescents by conicity index].
AB  - Body regional fat distribution has been linked with a metabolic atherogenic risk
      profile, that starts early in life. Data from a cross-sectional sample of 394
      boys and girls, 11 to 16 years, who inhabit a slum sector of Caracas, Venezuela
      was studied using Conicity Index (C): [equation: see text] by means of Box-plot
      diagram, Levene, ANOVA, and Scheffe tests. The accepted level of significance was
      p < 0.05. Results showed significant differences in body fat distribution between
      age groups. Height and body mass index were used as control variables. C values
      ranged between (1.02-1.18) in boys and (0.99-1.14) in girls. Boys attained higher
      mean values. All groups showed variance homogeneity (p value > 0.05) and sexual
      dimorphism was found at 11, 12 and 13 years, that were removed after controlling
      for height and body mass index. Differences according to age groups in boys, were
      removed after controlling for height. Results found conicity index as an
      alternative method to assess abdominal fat distribution during adolescents years.

PMID- 11460796
TI  - [Relation among early maturation, body mass index and the longitudinal behavior
      of systolic blood pressure].
AB  - In the Caracas Longitudinal Study, 53 girls- 8 to 11 years of age- who had been
      classified as early, average and late maturers were analyzed longitudinally with
      respect to Body Mass Index (BMI) and Systolic Blood Pressure (SBP). A
      longitudinal principal component analysis was used to summarize trends or
      intraindividual changes in BMI and SBP. A first component was identified for BMI,
      this component accounted for most of its total variance (94.65%). Girls were
      classified as normal in weight or at risk of overweight on the basis of this
      component. Three principal components were identified for SBP, that accounted for
      91.83% of the total variance of this variable. The first component represented a
      measure of position across the whole age period, a "canalization pattern"; this
      component accounted for most of the total variance (45.65%). The second component
      revealed an unidirectional change in relative position of the values of the
      variable, a "decanalization pattern", and a third pattern summarized deviations
      around a position level: "recanalization pattern". Girls who showed a
      canalization pattern for SBP were those identified as early maturers and at risk
      of overweight.

PMID- 11460797
TI  - [Changes in serum enzymes in rats treated with sodium bisulfite].
AB  - Inorganic sulfites are chemical compounds with antioxidative, antibacterial and
      antimycotic properties diffusely employed in agro-food and pharmaceutical
      industries. In spite of their continuous use there still are many questions
      regarding their safety, and their possible influence in several nutrients and
      enzymatic systems, as according to reports in the literature cited. In this study
      it is determined the effect of increasing doses of sodium bisulphite, 10 to 50
      mg/kg/day, injected intramuscularly during seven days on the activity of the
      following serum enzymes: phosphohexoseisomerase (PHI), gamma
      glutamyltranspeptidase (gamma-GT), cholinesterase (CHE), arginase, acid maltase
      (AM), alkaline phosphatase (AIP), lactic dehydrogenase (LDH), transaminases (GOT
      and GPT) and 5'-nucleotidase (5'-N) on male Wistar rats (treated groups). The
      results indicate that in rats treated with sodium bisulphite there is a
      significant increase (p < 0.05) in the activity of PHI, gamma-GT, arginase, AIP,
      GOT, GPT and 5'-N as well as an equally significant decrease (p < 0.05) in the
      activity of LDH, AM and CHE; these variations are proportional to the doses of
      the compound applied. These findings indicate there is cellular damage to rat
      liver, kidney or others organs as a result of bisulphite injected or by its
      metabolic derivatives. It is suggested that measurements of serum levels of LDH,
      AM and CHE are particularly helpful in the clinical assessment of pathologies
      caused by sulfites in allergology.

PMID- 11460798
TI  - Advances in pain.

PMID- 11460799
TI  - Phantom limb pain.

PMID- 11460800
TI  - Trigeminal neuralgia--pathophysiology, diagnosis and current treatment.

PMID- 11460801
TI  - Mechanisms of neuropathic pain.

PMID- 11460802
TI  - Chronic opioid therapy for non-cancer pain.

PMID- 11460803
TI  - Role of psychology in pain management.
AB  - Psychological factors are central to the experience of pain, the delivery of
      effective analgesia and for the specific treatment of chronic pain and
      disability. Improvement in pain management can often be brought about by very
      simple, if subtle, changes in clinical practice. Although simple, these changes
      can have significant effects in the experience of pain, distress and use of
      health-care resources. For the chronic pain patient, the presentation is much
      more complex and the treatment interdisciplinary and programmatic. The evidence
      for the effectiveness of cognitive behaviour therapy for adults with chronic pain
      is now well established. This treatment should be available as a core part of any
      chronic pain service.

PMID- 11460804
TI  - Anaesthesia and sleep apnoea.

PMID- 11460805
TI  - Anaesthesia and sleep apnoea.

PMID- 11460806
TI  - Perioperative beta-blockade.

PMID- 11460807
TI  - Right heart catheterization in intensive care.

PMID- 11460808
TI  - Internal jugular venous cannulation.

PMID- 11460809
TI  - Use of the laryngeal tube for nasotracheal intubation.

PMID- 11460810
TI  - Developments in local anaesthetic drugs.

PMID- 11460811
TI  - Mechanisms of inflammatory pain.

PMID- 11460812
TI  - Safety and efficacy of patient-controlled analgesia.

PMID- 11460813
TI  - Safety and efficacy of postoperative epidural analgesia.

PMID- 11460814
TI  - Effect of postoperative analgesia on surgical outcome.

PMID- 11460815
TI  - Analgesia for day-case surgery.

PMID- 11460816
TI  - Chronic pain after surgery.

PMID- 11460817
TI  - Complex regional pain syndrome.

PMID- 11460818
TI  - Oral antidiabetic treatment in patients with coronary disease: time-related
      increased mortality on combined glyburide/metformin therapy over a 7.7-year
      follow-up.
AB  - BACKGROUND: A sulfonylurea--usually glyburide--plus metformin constitute the most
      widely used oral antihyperglycemic combination in clinical practice. Both
      medications present undesirable cardiovascular effects. The issue whether the
      adverse effects of each of these pharmacologic agents may be additive and
      detrimental to the prognosis for coronary patients has not yet been specifically
      addressed. HYPOTHESIS: This study was designed to examine the survival in type 2
      diabetics with proven coronary artery disease (CAD) receiving a combined
      glyburide/metformin antihyperglycemic treatment over a long-term follow-up
      period. METHODS: The study sample comprised 2,275 diabetic patients, aged 45-74
      years, with proven CAD, who were screened but not included in the bezafibrate
      infarction prevention study. In addition, 9,047 nondiabetic patients with CAD
      represented a reference group. Diabetics were divided into four groups on the
      basis of their therapeutic regimen: diet alone (n = 990), glyburide (n = 953),
      metformin (n = 79), and a combination of the latter two (n = 253). RESULTS: The
      diabetic groups presented similar clinical characteristics upon recruitment.
      Crude mortality rate after a 7.7-year follow-up was lower in nondiabetics (14 vs.
      31.6%, p<0.001). Among diabetics, 720 patients died: 260 on diet (mortality
      26.3%), 324 on glyburide (34%), 25 on metformin alone (31.6%), and 111 patients
      (43.9%) on combined treatment (p<0.000001). Time-related mortality was almost
      equal for patients on metformin and on combined therapy over an intermediate
      follow-up period of 4 years (survival rates 0.80 and 0.79, respectively). The
      group on combined treatment presented the worst prognosis over the long-term
      follow-up, with a time-related survival rate of 0.59 after 7 years, versus 0.68
      and 0.70 for glyburide and metformin, respectively. After adjustment to variables
      for prognosis, the use of the combined treatment was associated with an increased
      hazard ratio (HR) for all-cause mortality of 1.53 (95% confidence interval [CI]
      1.20-1.96), whereas glyburide and metformin alone yielded HR 1.22 (95% CI 1.02
      1.45) and HR 1.26 (95% CI 0.81-1.96), respectively. CONCLUSIONS: We conclude that
      after a 7.7-year follow-up, monotherapy with either glyburide or metformin in
      diabetic patients with CAD yielded a similar outcome and was associated with a
      modest increase in mortality. However, time-related mortality was markedly
      increased when a combined glyburide/metformin treatment was used.

PMID- 11460819
TI  - One in four pregnant women in South Africa are HIV positive.

PMID- 11460820
TI  - Cheap HIV drugs for developing countries.

PMID- 11460821
TI  - Risks and benefits of gastric bypass in morbidly obese patients with severe
      venous stasis disease.
AB  - OBJECTIVE: To determine the risks and benefits of gastric bypass-induced weight
      loss on severe venous stasis disease in morbid obesity. SUMMARY BACKGROUND DATA:
      Severe obesity is associated with a risk of lower extremity venous stasis
      disease, pretibial ulceration, cellulitis, and bronze edema. METHODS: The GBP
      database was queried for venous stasis disease including pretibial venous stasis
      ulcers, bronze edema, and cellulitis. RESULTS: Of 1,976 patients undergoing GBP,
      64 (45% female) met the criteria. Mean age was 44 +/- 10 years. Thirty-seven
      patients had pretibial venous stasis ulcers, 4 had bronze edema, 23 had both, and
      17 had recurrent cellulitis. All had 2 to 4+ pitting pretibial edema. Mean
      preoperative body mass index (BMI) was 61 +/- 12 kg/m(2) and weight was 179 +/-
      39 kg (270 +/- 51% ideal body weight), significantly greater than in patients who
      underwent GBP without venous stasis disease. Two patients had a pulmonary embolus
      and four had Greenfield filters in the remote past. Additional comorbidities
      included obesity hypoventilation syndrome, sleep apnea syndrome, hypertension,
      gastroesophageal reflux, degenerative joint disease symptoms, type 2 diabetes
      mellitus, pseudotumor cerebri, and urinary incontinence. Comorbidities were
      significantly more frequent in the patients with venous stasis disease than for
      those without. At 3.9 +/- 4 years after surgery, patients lost 55 +/- 21 % of
      excess weight, 62 +/- 33 kg, reaching 40 +/- 9 kg/m(2) BMI or 176 +/- 41% ideal
      body weight. Venous stasis ulcers resolved in all but three patients.
      Complications included anastomotic leaks with peritonitis and death, fatal
      pulmonary embolism, fatal respiratory arrest, wound infections or seromas, staple
      line disruptions, marginal ulcerations treated with acid suppression, stomal
      stenoses treated with endoscopic dilatation, late small bowel obstructions, and
      incisional hernias. There were six other late deaths. CONCLUSIONS: Severe venous
      stasis disease was associated with a significantly greater weight, BMI, male sex,
      age, comorbidity, and surgical risk (pulmonary embolus, leak, death, incisional
      hernia) than in other patients who underwent GBP. Surgically induced weight loss
      corrected the venous stasis disease in almost all patients as well as their other
      obesity-related problems.

PMID- 11460822
TI  - Nomenclature for factors of the HLA system, update April 2001.

PMID- 11460823
TI  - Why is the prevalence of allergy and autoimmunity increasing?

PMID- 11460824
TI  - The response to plasmid DNA-virosome vaccination: a role for circulating
      antibodies?

PMID- 11460825
TI  - Insurmountable AT(1) receptor antagonism: the need for different antagonist
      binding states of the receptor.

PMID- 11460826
TI  - Re: Moderate controlled hypotension with sodium nitroprusside does not improve
      surgical conditions or decrease blood loss in endoscopic sinus surgery.

PMID- 11460827
TI  - Problems assaying neutrophil activators.

PMID- 11460828
TI  - Limited inferior macular translocation for the treatment of subfoveal choroidal
      neovascularization secondary to age-related macular degeneration.

PMID- 11460829
TI  - Clinical implications of the genetics of ALS and other motor neuron diseases.
AB  - Genetic mutations have been identified in the major motor neuron diseases,
      including ALS, spinal muscular atrophy, bulbospinal muscular atrophy (Kennedy's
      disease), the hereditary spastic paraplegias, and rarer conditions such as GM2
      gangliosidosis (hexosaminidase A deficiency). These include mutations in the SOD1
      gene, deletions of the telomeric copy of the SMN gene, expansions of the
      trinucleotide repeat region in the first exon of the androgen receptor gene,
      other rare mutations, and diseases where linkage has been established but the
      gene not identified. Identification of one of these genetic abnormalities will
      allow specific diagnosis in patients. Because cure is not yet available,
      presymptomatic testing is seldom indicated; in such cases, careful counseling is
      appropriate.

PMID- 11460830
TI  - [Botany. Antherozoids and double sexual reproduction in angiosperm plants. 1899].

PMID- 11460831
TI  - [New methods of coronary imaging II. Intracoronary ultrasonography in clinical
      practice].
AB  - Coronary angiography remains the standard technique for the assessment and
      therapy of coronary artery disease. Recently, intravascular ultrasound (IVUS) has
      emerged as a new adjunctive invasive tool which allows the acquisition of direct
      images of the atherosclerotic plaque in the cardiac catheterization laboratory;
      however it cannot be considered as an alternative to angiography. The aim of this
      article was to describe the indications, technique, and interpretation of IVUS
      imaging and its diagnostic and therapeutic applications, to review the pertaining
      literature and report the experience from our catheterization lab group.
      Ultrasound provides a unique method to study the regression or progression of
      atherosclerotic lesions in vivo. Lipid-laden lesions appear hypoechoic,
      fibromuscular lesions generate low-intensity or "soft echos" while the fibrous
      and calcified tissue impedes ultrasound penetration, obscuring the underlying
      vessel wall (acoustic shadowing). IVUS has been used to evaluate arterial
      remodeling: positive remodeling is the increase in arterial size to compensate
      for plaque accumulation and represents a compensatory mechanism to preserve lumen
      size; negative remodeling is vessel shrinkage and has been implicated in
      restenosis after balloon angioplasty. Positive remodeling seems to be
      significantly more frequent in myocardial infarction and unstable angina,
      negative remodeling occurs more often in stable coronary syndromes and is the
      main mechanism of restenosis after balloon angioplasty. In ostial and bifurcation
      lesion, the stenosis may be obscured by overlapping contrast-filled structures.
      Intermediate stenoses are particularly problematic in patients whose symptomatic
      status is difficult to assess. In these ambiguous situations, ultrasound provides
      a tomographic perspective, independent of the radiographic projection, which
      often allows precise lesion quantification. IVUS has emerged as the optimal
      method for the detection of diffuse post-transplant vasculopathy. Rapidly
      progressive intimal thickening (> 0.5 mm increase) in the first year after
      transplantation has major negative prognostic significance. The safety of IVUS is
      well documented, with studies reporting complication rates varying from 1 to 3%;
      the complications most frequently reported is transient spasm. Ultrasound allows
      us to evaluate plaque morphology, plaque eccentricity and lesion length, often
      helping in procedural decision-making. IVUS demonstrates plaque fracture and
      arterial wall dissection more often than angiography. Coronary angiograms
      frequently underestimate disease burden, whereas IVUS identifies residual plaque
      burden and minimal lumen diameter as the most powerful predictor of clinical
      outcome (restenosis). Several IVUS studies of directional atherectomy have
      addressed the issue of more aggressive plaque removal possibly resulting in
      decreased angiographic restenosis rate. IVUS imaging has played a pivotal role in
      the optimization of stent therapy. The concept of high-pressure stent
      implantation disseminated quickly, and larger trials demonstrated the safety of
      stent implantation using high pressures. IVUS has shown that in-stent restenosis
      is determined by the degree of intimal hyperplasia within the stent or in the
      stent border. In conclusion, the use of IVUS in the world is slowly increasing.
      Ultrasound commonly detects occult disease in patients with coronary artery
      disease. However, no short- or long-term studies have determined whether disease
      detected exclusively by ultrasound portends a worse prognosis as compared with
      "true normal" angiography.

PMID- 11460832
TI  - [New methods of functional assessment in the catheterization room. Pressure wire,
      Doppler flow wire and echocontrastomyography].
AB  - Although coronary angiography has been used for many years in the evaluation of
      coronary artery disease the limitations of this technique are well known. The
      functional significance of individual coronary artery stenoses may not be easily
      determined particularly in patients with intermediate stenoses, lesions with
      irregular and complex morphology and in subjects with multivessel diffuse disease
      and/or prior myocardial infarction. In selected patients, the role of
      abnormalities of vasomotion and function at the microcirculatory level cannot be
      assessed with lone coronary angiography. The functional evaluation of the results
      of percutaneous coronary interventions usually requires adjunctive non-invasive
      testing. New techniques for physiological evaluation of coronary artery disease
      are now available in the catheterization laboratory. The intracoronary pressure
      wires and Doppler flow wires may provide for an accurate evaluation of the
      functional significance of the individual stenosis and of the vasodilatory
      capacity of the coronary bed. Disease of the coronary microcirculation and
      vasomotion abnormalities may be recognized. Several studies have indicated that
      these techniques may be helpful in the clinical decision-making process. The
      strategy of deferring or performing percutaneous coronary interventions may be
      guided by on-line functional evaluation of the target stenosis and the result of
      interventions may be evaluated. In addition, new imaging modalities such as
      myocardial contrast echocardiography with new sonicated agents for intracoronary
      use may represent a novel approach to the direct evaluation of regional
      myocardial perfusion and microvascular integrity. The application of these
      techniques is safe, useful and cost-effective. Unfortunately, physiologic
      evaluation of the coronary artery disease by means of these techniques still
      remains confined to few catheterization laboratories.

PMID- 11460833
TI  - [Instability determinants of the carotid plaque: from histology to ultrasound].
AB  - Over the last decade, it has become progressively clear that the most important
      mechanism responsible for acute coronary and cerebrovascular events is
      atherosclerotic plaque rupture with superimposed thrombus formation. Anatomo
      pathological studies have shown that the risk of rupture depends on plaque type
      rather than plaque size. The determinants of carotid plaque vulnerability to
      rupture are similar to those responsible for coronary instability: 1) size and
      consistency of the lipid-rich atheromatous core, 2) ongoing inflammation and
      repair processes within the fibrous cap, and 3) the thickness of the fibrous cap
      covering the core. Unstable plaques contain a soft, lipid-rich core that is
      covered by a thin and inflamed cap of fibrous tissue. External factors such as
      mechanical and hemodynamic stresses may be important not only in precipitating
      disruption of vulnerable plaques, but also in their cellular differentiation.
      Several imaging techniques have been used to identify plaques at high risk of
      events. High-resolution B-mode ultrasound is a noninvasive, inexpensive technique
      which allows a characterization of carotid plaque dimension, internal structure
      and surface. Nevertheless, such a method is not perfect. The subjective
      evaluation of plaque morphology on B-mode ultrasound, the need of improving
      reproducibility and the lack of a uniform terminology are critical issues, which
      need to be addressed.

PMID- 11460834
TI  - [Evidence-based medicine: a critical analysis of the concept of evidence in
      medicine].
AB  - There is currently a lively debate involving scholars from diverse cultural
      background on the subject of evidence-based medicine. In order to set out the
      grounds of discussion this paper deals with the problem of "evidence", both the
      concept and meaning of this term. After a brief history of the idea of "evidence"
      from antiquity to the present day, it will be underlined how modern day thinking
      recognizes the existence of two types of "evidence": rational evidence supported
      first by Rene Descartes, and perceptible evidence, defended by Francis Bacon. In
      contemporary epistemology the idea of "evidence" has been conceived above all as
      perceptible and is closely linked to the idea of fact. The concept of "scientific
      fact" will therefore be analyzed and will reveal how in science, contrary to
      prevailing opinion, "pure facts" practically do not exist and how the "facts"
      which scientists talk about in their research are always "facts depending on
      theory". Subsequently the capacity of "facts" to prove scientific hypothesis will
      be examined. In the light of more recent epistemological reflection the thesis
      will be maintained according to which facts are not capable of definitively
      proving the truth of a theory. Such reflection leads to the conclusion that in
      medicine "evidence" is always dependent on the theoretical and practical context
      in which researchers work. In the final part of the paper the epistemological
      presumptions and ambitions of evidence-based medicine will be examined. This
      analysis concludes that the epistemology on which evidence-based medicine relies
      upon does not grasp the true complexity of the scientific methodology and can
      weaken in doctors the beneficial stimulus that is doubt.

PMID- 11460835
TI  - [Interaction between respiration, autonomic function, and respiratory pattern in
      heart failure. New possibilities of rehabilitation intervention].
AB  - Some of the most invalidating symptoms in subjects with chronic heart failure,
      such as dyspnea and poor exercise tolerance, correlate poorly with indices of
      myocardial pump function, but are more related to alterations in autonomic
      nervous system, respiratory system, in addition to physical deconditioning.
      Increasing evidence suggests that in addition to pump function abnormalities,
      sympathetic and parasympathetic abnormalities, increased function of baro-, chemo
      and ergoreflex control mechanisms play a pivotal role in the origin of symptoms
      in these patients, potentiating the mechanisms leading to physical deconditioning
      and further worsening of symptoms. This underlines the practical importance of
      studies focused on the possibility of modifying these control mechanisms. Recent
      evidence indicates that non-pharmacological interventions, such as general
      physical training, or, particularly, specific types of training of the
      respiratory pattern, may modify some of these reflex control mechanisms,
      including the chemoreflex response, and provide potential favorable effects in
      chronic heart failure.

PMID- 11460836
TI  - [Role of inflammation mediators in the pathogenesis of heart failure].
AB  - A number of factors are involved in congestive heart failure pathogenesis. Among
      these, inflammatory mediators could have a crucial role. Patients with congestive
      heart failure show increased plasma levels of "proinflammatory cytokines", in
      particular tumor necrosis factor-alpha and interleukin-6. Clinical and
      experimental models have demonstrated that these cytokines induce left
      ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle
      abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the
      possibility that increased plasma concentration of cytokines could not be just an
      epiphenomenon, but an effective pathogenetic mechanism of disease progression.
      Additional inflammatory proteins involved in the acute phase response could play
      a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long
      pentraxin, structurally related, although with different functions, to C-reactive
      protein, is produced by immune system cells, fibroblasts and particularly by
      cardiac endothelial cells and myocytes, as demonstrated in murine and human
      models. Its synthesis is rapidly induced after exposition to bacterial
      lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor
      necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the
      acute local inflammatory response to myocardial injury (e.g. necrosis) and in
      heart failure pathogenetic mechanisms, but its exact role is not yet settled.
      Defining the specific part played by these molecules in the pathogenesis of heart
      failure could lead to new therapeutic approaches in the treatment of cardiac
      insufficiency.

PMID- 11460837
TI  - [Medico-legal features of early discharge in acute myocardial infarction and
      chest pain].
AB  - The authors' aim is to outline some of the main medico-legal problems in
      cardiology, especially those regarding the premature hospital discharge of
      patients with undefined chest pain and/or with acute myocardial infarction. After
      a brief overview on the etiology and clinical definition of chest pain and
      myocardial infarction, premature hospital discharge is defined and the incidental
      medico-legal risks that physicians operating in such situations are exposed to
      are pointed out. Next, the profiles regarding both the positive and negative
      views of professional medical responsibility are described. In the negative
      frame, the authors outline the most frequent civil and penal aspects of the
      unpremeditated responsibility. Then the physician's error, in both qualitative
      (generic or specific guilt) and quantitative (degree) terms, is considered;
      particularly, negligence, imprudence and inexperience, as qualitatively accepted
      meanings of generic guilt, are dealt with by adopting illustrative cases settled
      in the light of the right legal interpretation. The phases of the diagnostic or
      prognostic error are evaluated, and clinical protocols, as a reference parameter
      for the identification of error, are considered. Lastly, the problem of
      causality, essential condition for the judgment about the professional
      responsibility, and the problem of the patient's consent, including an evaluation
      of the legal capability or incapability about the declaration of consent, are
      examined closely.

PMID- 11460838
TI  - [ANMCO genetic area. Significance of family history in cardiology--Part III].
AB  - This is a proposal for collecting the family history throughout a guided form to
      be given to the patient when awaiting for ambulatory examination or hospital
      admission, before meeting the cardiologist. In this form, the patient is asked to
      make an effort in order to focus on his family history (diseases, signs,
      symptoms, medications, etc.) at least for parents, sibs, and off-springs. A nurse
      should be committed to give the form to the patient, making him sure that the
      incomplete filling does not limit the quality of the diagnostic and therapeutic
      work-up. Thanks to the guided form, the patient concentrates the attention on his
      family history, eventually consulting the relatives before being examined. The
      form opens stating that all data are potentially helpful, but none is essential
      for diagnosis and treatment. This new approach to the family history could
      support clinicians in having helpful news, only deepening information that seems
      to be more relevant for the diagnosis.

PMID- 11460839
TI  - [Cost of diagnostic and therapeutic hemodynamic procedures: comparison with DRG
      reimbursement].
AB  - BACKGROUND: The cumulative costs of diagnostic and interventional procedures in
      the catheterization laboratory in public hospitals are still largely unknown,
      notwithstanding the present stress upon the cost-effectiveness issues in
      medicine. METHODS: From January through April 2000 we have evaluated procedures
      in the catheterization laboratory of the Ravenna USL. Costs taken into
      consideration were the following: the mean cost of materials for each type of
      examination and of medications used for each patient, personnel costs, machinery
      mortgages' costs, ambulance transportation's costs, and general hospital
      expenditures. DRGs and reimbursements have been calculated on the basis of
      clinical indications and modalities of procedures. RESULTS: During the evaluation
      period 268 patients have been studied. The procedures taken into consideration
      included: 135 coronary angiographies, 36 right and left catheterizations plus
      coronary angiography, 87 coronary angiographies plus percutaneous coronary
      intervention (PCI), 10 PCI. The total cost of diagnostic catheterization was Itl
      1,226,000 (Euro 632) whereas that of each PCI (including stent implantation in
      80% of cases) associated in 87 cases with coronary angiography was Itl 5,956,000
      (Euro 3044). Patients with an acute coronary syndrome or heart failure were
      mostly studied during their first hospital stay; those with stable disease
      (stable angina, previous myocardial infarction, valvular heart disease or
      cardiomyopathy without heart failure) were studied during ordinary hospital
      admission or in the context of a day-hospital. DRGs and corresponding
      reimbursements for the different clinical situations were the following: unstable
      angina DRG 124 valued at Itl 6,180,000; stable angina DRG 125 valued at Itl
      3,900,000; acute or recent myocardial infarction with or without complications
      DRG 121 or 122 valued at ItI 8,290,000 or Itl 5,900,000; heart failure in
      valvular heart disease or cardiomyopathy DRG 124 valued at Itl 6,180,000;
      valvular heart disease or cardiomyopathy DRG 125 valued at Itl 3,900,000. The DRG
      for a PCI is no. 112 valued at Itl 10,235,000. CONCLUSIONS: The costs of
      diagnostic and interventional hemodynamic procedures were acceptable and
      proportional to the DRG-related reimbursements. Appropriately indicated
      procedures and their quick execution during the first hospital stay lead to
      global economic savings for the health care system and are also clinically
      advantageous for the individual patient.

PMID- 11460840
TI  - [Left monoventricular assistance with DeBakey VAD continuous flow pump: initial
      clinical Italian experience].
AB  - BACKGROUND: The shortage of heart donors causes a rise in mortality among
      candidates for cardiac transplantation and increases the waiting list.
      Consequently mechanical circulatory support for bridge to transplant is now a
      standard clinical procedure utilized in the most representative cardiac surgery
      centers. Recently, continuous-axial-flow pumps have been introduced in the
      clinical practice and have led to new perspectives. METHODS: Four patients
      suffering from end-stage heart failure were implanted with a DeBakey ventricular
      assist device (VAD) continuous-flow pump as a bridge to heart transplant. The
      DeBakey VAD is smaller than the pulsatile devices commonly employed, the pump is
      totally implantable and is connected to a small controller and two batteries by a
      transcutaneous drive line. RESULTS: One patient died of multiorgan failure during
      assistance; 3 patients were fully rehabilitated and were successfully
      transplanted after 55, 42 and 141 days respectively. In the early postoperative
      period the mean pump flow was 4.27 +/- 0.55 l/min, after 1 week of assistance the
      flow rose to 5.32 +/- 0.57 l/min and then progressively increased to 5.83 +/-
      0.57 l/min. CONCLUSIONS: This experience demonstrated the possibility of
      continuous-flow left ventricular support with the DeBakey VAD for mid-term
      mechanical ventricular assistance. This pump presents new interesting aspects and
      opens new perspectives for the future of left ventricular mechanical assistance.
      Increasing experience will define the role of this device in the scenario of
      heart failure.

PMID- 11460841
TI  - [Chest pain and acute myocardial infarction at the emergency department:
      diagnostic and therapeutic approaches. Experience of the San Camillo Hospital in
      Rome].
AB  - BACKGROUND: Identification and treatment of patients with acute chest pain due to
      acute coronary syndrome is a common and difficult challenge for emergency
      physicians. The aim of this study was to establish: a) the reliability of
      diagnosis of acute myocardial infarction met in the emergency ward, b) the length
      of the patient's hospital stay with acute myocardial infarction discovered and
      treated in the emergency ward either with primary angioplasty or with
      thrombolysis. METHODS: We analyzed the data collected in the emergency ward of
      the San Camillo Hospital in Rome from January 1 to June 30, 2000, with patients
      suffering from chest pain and diagnosis after hospitalization. The reliability of
      diagnosis of acute myocardial infarction was calculated from the comparison of
      the diagnosis in the emergency ward and the diagnosis at hospital discharge.
      RESULTS: From January 1 to June 30, 2000, 45,810 patients have asked for help at
      the emergency ward; 2334 (5.1%) of these were suffering from chest pain. The
      diagnosis of acute myocardial infarction was done in the emergency ward in 147
      cases (141 hospitalized, 4 deceased, and 2 transferred to other hospitals), equal
      to 65% of all those discharged with the same diagnosis in the period under
      examination. In 66 out of the 141 cases hospitalized (46.8%) primary angioplasty
      was successfully performed; in 14 (9.9%) only coronary angiography was performed
      (primary angioplasty unfeasible); in 22 (15.6%) thrombolysis was administered
      whereas in 38 cases (27.0%) other treatments were used. The average stay for the
      different groups turned out to be 9.8 +/- 4 days for primary angioplasty and 12.9
      +/- 4 days for thrombolysis: the difference was relevant. CONCLUSIONS: The
      accuracy value of the diagnosis of acute myocardial infarction made in the
      emergency ward of our Hospital is the same as that published in the international
      literature and demonstrates the high level of treatment of chest pain.
      Furthermore, the shorter hospital stay obtained by primary angioplasty in
      comparison with thrombolysis seems to strengthen the already favorable cost
      benefit ratio of primary angioplasty in comparison with thrombolysis.

PMID- 11460842
TI  - [Reversibility of left ventricular dysfunction in elderly patients with dilated
      cardiomyopathy undergoing treatment with carvedilol. Report of a case].
AB  - Owing to recurrent episodes of congestive heart failure, an 88-year-old man with
      moderate aortic stenosis and dilated cardiomyopathy was treated with carvedilol
      and closely followed up. At the beginning of the treatment the patient was in
      NYHA functional class IV and presented with severe global left ventricular
      hypokinesia with an ejection fraction of 15%. Carvedilol was started at a dose of
      3.125 mg twice daily and progressively increased to 12.5 mg twice daily. Six
      months later the left ventricular volumes had become almost normal, wall motion
      abnormalities had completely reversed and the ejection fraction was markedly
      increased (62%). The patient was classified in NYHA functional class II. This
      case shows the recovery of left ventricular systolic function during the
      administration of carvedilol in an old patient with dilated cardiomyopathy and
      chronic congestive heart failure.

PMID- 11460843
TI  - [Rupture of the interventricular septum in lower myocardial infarction with
      asymptomatic onset].
AB  - We report the case of a 69-year-old patient with no history of cardiac problems
      referred to us for dyspnea. A major systolic murmur was found and the
      echocardiogram revealed an interventricular septal defect. The ECG showed no
      signs of acute myocardial infarction that was established on the basis of
      myocardial enzymes. The patient was hemodynamically stabilized by intra-aortic
      balloon pumping. A later coronarography revealed one-vessel coronary artery
      disease. Then the patient underwent successful surgical repair of the septal
      defect.

PMID- 11460844
TI  - [Large thrombus in non-aneurysmal descending aorta and peripheral embolism:
      report of a case and review of the literature].
AB  - We describe the case of a middle-aged woman with massive thrombosis of the aortic
      bifurcation, treated with emergency surgery. The patient was later evaluated by
      transthoracic echocardiography, which resulted normal, and by transesophageal
      echocardiography, which demonstrated a huge thrombus in the lumen of the
      descending thoracic aorta, in the absence of gross vessel wall abnormalities.
      Thus, the patient underwent a second surgical intervention and the thrombus was
      successfully removed. The episode led us to review the medical literature about
      cases of thrombosis and embolization originating from macroscopically normal
      aortas. This review underscores the diagnostic yield of the transesophageal study
      of the aorta in patients with systemic embolization (particularly in the presence
      of risk factors for atherosclerosis) and supports a wider indication of
      transesophageal echocardiography in the evaluation of systemic embolizating
      syndromes.

PMID- 11460845
TI  - [The Primary Prevention Project Study Group. Low-dose aspirin and vitamin E in
      people at cardiovascular risk: a randomized trial in general practice].

PMID- 11460846
TI  - [Cardiovascular disease and mortality in older adults with small abdominal aorta
      aneurysm detected by ultrasonography. The Cardiovascular Health Study].

PMID- 11460847
TI  - [Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate
      alcohol consumption on myocardial infarction].

PMID- 11460848
TI  - [Longitudinal assessment of neurocognitive function after coronary-artery bypass
      surgery].

PMID- 11460849
TI  - [Beneficial effects of pentoxifylline in patients with idiopathic dilated
      cardiomyopathy treated with angiotensin-converting enzyme inhibitors and
      carvedilol. Results of a randomised study].

PMID- 11460850
TI  - Predictive factors of social disability in patients with eating disorders.
AB  - OBJECTIVE: The study was designed to assess whether social avoidance symptoms
      and/or comorbid anxiety disorders were predictive factors of social disability in
      subjects with eating disorders. METHOD: Sixty-three subjects with anorexia
      nervosa or bulimia nervosa were assessed for lifetime diagnoses of anxiety
      disorders, childhood history of separation anxiety disorder, social avoidance
      symptoms and social disability. RESULTS: On the Groningen Social Disabilities
      Schedule, 86% of the anorexics and 65% of the bulimics had disability regarding
      the 'social role', and 86% and 61 % disability regarding the 'occupational role'.
      Using all subsets logistic regression analyses, predictive factors of disability
      were: (1) for the social role, social avoidance symptom score (p<0.002) and
      diagnosis of separation anxiety disorder (p<0.01); (2) for the occupational role,
      number of lifetime anxiety disorders (p<0.01) and diagnosis of separation anxiety
      disorder (p<0.06). DISCUSSION: Recognizing and treating comorbid anxiety
      disorders in subjects with eating disorders could improve social adaptation and
      global psychopathological outcome.

PMID- 11460851
TI  - Monoclonal antibody to tumor necrosis factor-alpha reduces hypergastrinemia in
      Helicobacter pylori infection.

PMID- 11460852
TI  - Pure red aplasia as the first manifestation of systemic lupus erythematosus.

PMID- 11460853
TI  - Acute myelocytic leukemia and human immunodeficiency virus infection.

PMID- 11460854
TI  - Sweet's syndrome and bronchiolitis obliterans organizing pneumonia.

PMID- 11460855
TI  - Hemighost cell in acute hepatitis A: glucose-6-phosphate deficiency revisited.

PMID- 11460856
TI  - Community-acquired pneumonia caused by Enterobacter asburiae.

PMID- 11460857
TI  - Kidney stones and cystic fibrosis.

PMID- 11460858
TI  - Historical note: Early history of the anthropometry of body composition.
AB  - A pioneering paper outlining an anthropometric approach to the study of body
      composition, written by the Czech anthropologist Jindrich Matiegka, was published
      in the American Journal of Physical Anthropology in 1921. For a long time we have
      searched for information about the history of the idea and of the paper itself.
      In recent years, we were able to identify relevant correspondence in the archives
      of the Smithsonian Institution of Washington.

PMID- 11460859
TI  - Assessing the influence of physical activity on health and fitness.
AB  - Increasing rates obesity and related chronic diseases in the United States and
      other parts of the world appear to be partly attributable to declining levels of
      physical activity. Given that adult obesity and chronic diseases often have their
      origins in childhood, there is a critical need to better understand how activity
      and fitness levels in childhood and adolescence shape health status in adulthood.
      The four papers in this series on physical activity draw on several longitudinal
      studies to examine the relationships between levels of physical activity and
      health-related fitness in childhood and adolescence to those in adulthood. These
      studies consistently demonstrate that adult activity levels and associated health
      outcomes are only modestly correlated with activity and fitness measures from
      childhood and adolescence. However, it appears that the methodological
      limitations in measuring activity levels may result in an underestimation of the
      importance of the influence of physical activity on health. Newer methods of
      measuring activity and energy expenditure offer to substantially improve our
      understanding of the influence of activity patterns on human health and fitness.
      Such information is necessary for promoting lifestyle changes that will reduce
      the risks of obesity and other chronic diseases.

PMID- 11460860
TI  - Physical activity and fitness: pathways from childhood to adulthood.
AB  - Contemporary thinking in public health posits that childhood and adolescent
      physical activity and physical fitness may influence health status during
      childhood and adolescence, as well as throughout adulthood. This paper addresses
      the evidence dealing with potential associations of physical activity and
      physical fitness in childhood and adolescence to health status during childhood,
      adolescence, and adulthood. There are generally low to moderate relationships
      between childhood and adolescent physical activity and health (operationalized
      largely in terms of health-related physical fitness) and adult physical activity
      and health. A large part of the variability in health-related fitness is not
      accounted for by physical activity as assessed in the available studies.
      Nevertheless, the trends emphasize the importance of a lifestyle of regular
      physical activity during childhood and adolescence, which continues into and
      throughout adulthood, for the health and well-being of the individuals and
      populations.

PMID- 11460861
TI  - Adolescent physical performance and adult physical activity in Flemish males.
AB  - Limited information is available about the associations between adolescent
      fitness levels and adult physical activity. In the present study, these
      associations are investigated using different indicators of physical activity. It
      is hypothesized that both health- and performance-related fitness
      characteristics, observed during the adolescent period, contribute equally to the
      explained variance in adult physical activity levels. Subjects were 109 Flemish
      males followed over a period of 27 years from 13 to 40 years of age in the Leuven
      Longitudinal Study on Lifestyle Fitness and Health. Performance and health
      related fitness characteristics were observed during the growth period and at 40
      years of age. The Work Index, Leisure Time Index, and Sport Index of the Baecke
      questionnaire were used as indicators of physical activity together with triaxial
      accelerometry. Multiple regression and discriminant analyses contrasting extreme
      quintiles of activity groupings were used to analyse the associations. Only the
      Baecke Sport Index showed consistent significant associations (R2 = 0.03 to R2 =
      0.23) with adolescent fitness levels observed at 13, 15, and 18 years. When upper
      and lower quintiles were contrasted, fitness characteristics observed at the
      three age levels during adolescence were significantly different for each of the
      three indices of the Baecke questionnaire at 40 years of age. Lowest associations
      (R2 = 0.09 to R2 = 0.17) were found for the Work Index, followed by the Leisure
      Time Index (R2 = 0.12 to R2 = 0.28) and Sport Index (R2 = 0.25 to R2 = 0.43).
      Highest associations were evident for the 18- to 40-year interval. Performance-
      and health-related fitness characteristics explain equally well the variance in
      physical activity indicators.

PMID- 11460862
TI  - Adolescent motor skill and performance: is physical activity in adolescence
      related to adult physical fitness?
AB  - In the Amsterdam Growth and Health Longitudinal Study (AGAHLS), a cohort of about
      400 boys and girls (mean age 13 years) were followed over a period of 20 years.
      Over that period repeated measurements were done of body dimensions (height,
      weight, skinfolds), physical fitness (eight motor performance field tests: plate
      tapping, bent arm hang, 10 x 5 m sprint, arm pull, sit and reach, standing high
      jump, 10 leg lifts, 12-min endurance run, and one laboratory test to measure
      maximal aerobic power), and physical activity (by a cross-check interview). Three
      research questions were studied: (1) Is there a positive relationship between
      adolescent fitness (age 13-17 years) and adult physical activity (age 33 years)?
      (2) Do physical fitness and physical activity track from adolescence into
      adulthood? (3) What is the longitudinal relationship between physical fitness and
      physical activity? Multiple linear regression analysis showed that of the 9
      physical fitness tests, only the 12-min endurance run and the maximal aerobic
      power during adolescence are significant (P < 0.05) predictors of adult physical
      activity. The effects are not influenced by biological age but by sex: only in
      females are the predictions significant (P < 0.05) Tracking over the period of 20
      years estimated from stability coefficients showed values for physical fitness
      varying between 0.83 (plate tapping) to 0.38 (standing high jump and maximal
      aerobic power). Physical activity shows lower stability coefficients (0.35-0.29).
      A longitudinal linear regression technique was used to analyse the relationship
      between physical activity and physical fitness over the 20-year period; in this
      analysis corrections were made for both time-dependent (time, biological age, and
      cardiovascular factors) and time-independent variables (sex). All physical
      fitness tests show positive and significant (P < 0.05) standardized regression
      coefficients with physical activity, but the explained variance is less than 1%.
      Only maximal aerobic power has a higher explained variance of 1.8%. It can be
      concluded that: (1) Physical fitness in adolescence is only weakly related to
      adult physical activity; (2) between age 13 and 33 years, physical activity has
      low stability and physical fitness was higher stability; and (3) the longitudinal
      relationships between physical fitness and physical activity are only meaningful
      with maximal aerobic power.

PMID- 11460863
TI  - Prediction of physical activity and physical work capacity (PWC150) in young
      adulthood from childhood and adolescence with consideration of parental measures.
AB  - The 12-year prediction of physical activity level and submaximal aerobic fitness
      observed during young adulthood was quantified from childhood and parental
      measures. The sample consisted of 153 children and adolescents of the Quebec
      Family Study who were evaluated at baseline and reassessed 12 years later, as
      young adults. Physical work capacity at a heart rate of 150 beats x min(-1)
      (PWC150) was measured using cycle ergometry. A 3-day activity record was used to
      estimate daily energy expenditure (DEE), inactive time (IA), and time spent in
      moderate-to-vigorous activity (MVPA). Spearman partial inter-age correlations,
      controlling for length of follow-up and age at baseline, indicated better
      tracking for PWC150 (0.24 and 0.46, males and females, respectively) than for
      indicators of physical activity (0.07 < or = r < or = 0.25, males; 0.06 < or = r
      < or = 0.22, females). Multiple regression analyses indicated that parental
      measurements of activity and PWC150 did not add any predictive value, with the
      exception of paternal DEE, which accounted for 8% of the variance in males. There
      is moderately high stability of submaximal work capacity and lower tracking of
      physical activity from childhood and adolescence into young adulthood.

PMID- 11460864
TI  - Components of length growth variation in infants from the same population but
      different environments.
AB  - Growth in length of infants in Khartoum is profoundly related to whether or not
      their mothers are in paid employment. Some of this relationship appears to be due
      to levels of infectious disease, which are much higher in the infants of working
      mothers. Exponential decay curves do not fit longitudinal measurements of length
      growth particularly well in either group of infants, but they do yield
      distinctive temporal patterns of residuals. Simulation demonstrates that these
      patterns accord with a "catch-down" form of growth in infants of working mothers
      and a "catch-up" form in infants of housewives. Attempts to allow for these
      phenomena by providing for the opportunity of a single pulse of negative sine
      form in the former and a similar pulse of positive sine form in the latter
      reduces the level of residuals and tends to reduce temporal pattern in them. Most
      strikingly, it leads to average growth curves for the two groups of children
      becoming almost identical. It is hypothesized that these decay curves represent
      the underlying curves of infant growth in Khartoum free from the effects of
      environmental variation.

PMID- 11460865
TI  - Age-related decline in body cell mass in elderly men and women, determined by a
      noninvasive nuclear technique: effects of physical activity and dietary potassium
      intake.
AB  - The body cell mass (BCM) represents the actively metabolizing cellular components
      of the human body. In this study, the hypothesis was tested that physical
      activity and a sufficient dietary intake of potassium attenuate the age-related
      decline in BCM in the elderly. Cross-sectional data were collected in 82 male and
      79 female non-institutionalized elderly (60-90 years) from Mainz, Germany, and
      were analyzed by age groups. BCM was calculated from total body potassium,
      measured by whole-body counting of naturally occurring 40K. Physical activity
      level (PAL) was assessed by a standardized questionnaire. Dietary intake of
      potassium (DIP) was estimated from a 7-day food diary. The results showed the
      following trends: (1) BCM decreased continuously from age 60 to 90 years by 11.2%
      (men) and 7.0% (women). BCM was inversely correlated with age in both sexes (men,
      P < 0.001; women, P < 0.05), but significant age group differences only existed
      for men (P < 0.01, one-way analysis-of-variance). Women had less BCM than men in
      all age groups (P < 0.001, t tests). (2) Correlation analyses demonstrated that
      in both sexes PAL declined with advancing age (P < 0.05), whereas DIP did not
      change significantly with age. (3) In both sexes, BCM showed a strong positive
      correlation with PAL (P < 0.001), but did not correlate significantly with DIP.
      Multiple linear regression analysis (independent variables were PAL, DIP, age,
      height, weight) demonstrated that PAL, age, and height explained 45% of the
      variability in BCM in men. In women, PAL was the only significant predictor of
      BCM, explaining 23% of the variance. The study supports the hypothesis that the
      level of physical activity is associated with the decline of BCM in the elderly.

PMID- 11460866
TI  - Seventy-three nuclear DNA polymorphisms in a Spanish population and a comparison
      with ten other populations.
AB  - An anthropologically well-defined Spanish sample from La Alpujarra (SE Spain) was
      analyzed for 73 nuclear DNA polymorphisms. The population was chosen on the basis
      of available information on its history and demographic characteristics making it
      suitable for comparisons with data from North African populations. The Moslem
      invasion in this area was longer than anywhere in the Iberian Peninsula (more
      than nine centuries). The markers analyzed have been studied previously in 10
      human populations from different continents. The Alpujarrenian population was
      checked for these markers and it is the one with the highest number of
      chromosomes analyzed. Two new alleles were sized and heterozygosity levels were
      very similar to other European populations. Genetic distances closely matched
      geographical relationships both with neighbor joining tree and principal
      component analysis. Allele distributions revealed specific associations with some
      populations. This work reveals the importance of these markers for evolutionary
      studies of human populations.

PMID- 11460867
TI  - Frequency of twinning in two Costa Rican ethnic groups: an update.
AB  - Variation in the frequency of twinning among human populations has been presumed
      to reflect genetic differences. It has been commonly reported that populations of
      African ancestry have the highest, those of Asian ancestry the lowest, and those
      of European and Middle-Eastern ancestry intermediate frequencies of twinning.
      Populations from the Americas have been reported to have intermediate twinning
      frequencies, presumably reflecting their admixture. In this context, Madrigal
      (1994. Am J Hum Biol 6:215-218) reported virtually identical (and high) twinning
      frequencies in two Costa Rican ethnic groups, one of African, the other of Euro
      Amerindian ancestry. These frequencies were interpreted in light of frequent
      inter-ethnic unions, and it was predicted that the two groups would not differ
      substantially in gene frequencies of several blood enzyme systems. This paper
      reports the gene frequencies of both groups for such systems. The samples differ
      significantly for systems that have clearly different frequencies in African and
      European populations. Given that the groups are actually different in gene
      frequencies and not homogenous as predicted earlier, the conclusion that twinning
      frequencies are similar as a result of a similar genetic make up can be
      questioned. The results challenge the assumption that if populations have similar
      twinning frequencies it is because they are genetically similar and argue for a
      stronger environmental component for twinning frequencies.

PMID- 11460868
TI  - Blood pressure and sexual maturity in adolescents: the Heartfelt Study.
AB  - This study investigates sexual maturity as a predictor of resting blood pressures
      independent of other known predictors, in 179 boys and 204 girls 11-16 years of
      age from the Heartfelt Study. The sample included youth of African (n = 140),
      Mexican (n = 117), and European and "other" (n = 126) backgrounds. Sexual
      maturity was assessed during clinical examination of three standard indicators
      for each sex. Systolic and diastolic blood pressures were higher in children of
      maturity stages IV and V, compared to stages I-III, in each gender/ethnic group
      (P < 0.01 in almost all groups). Boys and girls advanced in sexual maturity for
      their age group, had significantly higher systolic blood pressures (but not
      diastolic) than the less advanced in linear models that included height, body
      mass index (BMI), ethnicity, and age as co-predictors. Diastolic blood pressures
      were predicted by height in boys and by age and the BMI in girls. This analysis,
      using a very conservative approach, suggests that sexual maturity provides
      important and independent information on systolic blood pressure in adolescents.
      Further investigation of its role in 24-hr blood pressures and in blood pressures
      taken during physical and emotional stress, is recommended.

PMID- 11460869
TI  - Cybernetic aspects of bone modeling and remodeling, with special reference to
      osteoporosis and whole-bone strength.
AB  - Assume mythical physiologists were taught that renal physiology and its disorders
      depend on "kidney cells" and their regulation by nonmechanical factors, but were
      taught nothing about nephrons. For decades they "knew" that idea was correct,
      just as Ptolemy "knew" the universe centers on our planet. But then others began
      to describe nephrons, their roles in renal physiology and disorders, and problems
      they revealed in former views, so doubts and controversies began. Today real
      physiologists encounter a similar situation for bone health and its disorders. A
      1960 paradigm attributed such things to bone's effector cells (osteoblasts and
      osteoclasts) and their regulation by nonmechanical factors, without "nephron
      equivalent" or biomechanical input. But both mechanical and nonmechanical factors
      regulate bone's nephron equivalents. Adding features of those equivalents to the
      1960 views led to the Utah paradigm, which suggests problems in former views and
      better explanations for "osteoporosis," whole-bone strength, and other bone
      disorders. Such things incited controversies among current skeletal
      physiologists. Cybernetics concerns the relationships, mechanisms, signals, and
      message traffic that help to control the behavior and other features of dynamic
      systems. A cybernetic analysis of the bone physiology in the Utah paradigm can
      add many features to the 1960 paradigm that help to understand osteoporoses,
      other bone disorders, and whole-bone strength (and bone mass). The added features
      also show new and pertinent targets for the related research.

PMID- 11460870
TI  - Assessing the body composition of 6-17-year-old Black and White girls in field
      studies.
AB  - The purpose of the study was to develop ethnic-specific equations for fat-free
      mass (FFM) from selected anthropometric dimensions and bioelectrical impedance
      measures of resistance (R) and reactance (Xc) for use in the NHLBI Growth and
      Heath Study. Using dual-energy X-ray absorptiometry measures of body composition
      as the dependent variable and field measures of body composition by anthropometry
      and bioelectrical impedance as the explanatory variables, ethnic-specific
      prediction equations were developed on a sample of girls representing a wide
      range of ages and BMI. The equations were cross-validated using (1) the
      Prediction of Sum of Squares (PRESS) statistic and (2) an independent sample of
      20 girls of each race from a study conducted at the National Institute of Child
      Health and Human Development (NICHD). Subjects were 65 White and 61 Black girls 6
      17 years of age. The best race-specific equations for FFM each explained 99% and
      97% of the variance in the White and Black girls, respectively. Root mean square
      errors (RMSE) ranged from 1.14 to 1.95 kg. The equation for Black girls used
      Stature2/Resistance (R), weight, and reactance (Xc) as predictor variables; the
      equation for White girls used Stature2/R, weight, and triceps skinfold thickness.
      The results indicate that (1) equations to predict FFM in girls should be ethnic
      specific and that (2) accurate values for TBF and %BF can be calculated from the
      predicted FFM.

PMID- 11460871
TI  - Validity and reliability of self-reported stature and weight of US adolescents.
AB  - Validity and reliability of self-reported stature and weight were investigated
      for U.S. adolescents (12.0-17.0 years) who were participants in the Third
      National Health and Nutrition Examination Survey (NHANES III). Data were
      collected on 1,635 youth and were statistically weighted to represent the
      national population. Self-reported weights are missing from 40% of 12 year olds
      and 25% of 13 year olds. Those who refused or were unable to provide self
      reported weights were younger, shorter, and lighter than those who did. Among
      those who provided self-reports, the average bias and random error in reporting
      were largest for the youngest youth. Biases in reporting stature and weight were
      consistently negative following the NHANES III protocol. The intraclass
      coefficients between measured and self-reported dimensions within age and gender
      groups ranged from 0.57 to 0.91 and from 0.85 to 0.98, for stature and weight,
      respectively. Self-reported stature and weight are not recommended as proxies for
      measured dimensions for youth less than 14 years of age.

PMID- 11460872
TI  - Early postnatal growth of low birthweight infants in the WIC program.
AB  - Patterns of early postnatal growth were analyzed among low birthweight infants
      enrolled in the Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC). Infants were divided into four groups according to their neonatal
      status: (1) term, normal birthweight (NBW); (2) term, low birthweight (LBW); (3)
      moderately preterm LBW; and (4) very preterm LBW. Comparison of mean weight and
      length z-scores indicated that term NBW and very preterm LBW infants were at or
      near the national reference averages at 8, 12, and 18 months. Term LBW and
      moderately preterm infants were lighter and shorter than the other two study
      groups at each visit. Term LBW and moderately preterm infants displayed evidence
      of catch-up growth during the study period. Catch-up growth was defined as a
      decrease in the percentage of infants below the 10th percentile for weight. The
      effect of neonatal body proportions on postnatal growth was investigated in term
      LBW infants. The infants were divided into two groups based on their ponderal
      index (PI) at birth (low PI and proportionate PI). Comparison of weight and
      length z-scores indicated that both groups of term LBW infants improved in z
      scores between birth and the first visit (approximately 8 months). However,
      infants with evidence of asymmetric intrauterine growth restriction (low PI)
      continued to improve in weight and length z-scores, whereas those with symmetric
      growth restriction (proportionate PI) remained lighter and shorter.

PMID- 11460873
TI  - Age and perceived stress independently influence daily blood pressure levels and
      variation among women employed in wage jobs.
AB  - The purpose of this study was to examine whether age and perceived stress were
      independent factors affecting blood pressure variation associated with changing
      daily microenvironments among women employed outside the home. The subjects of
      this study were 91 women from the same workplace (age 33.8 +/- 8.5 years; range
      18.2-49.3 years) who wore an ambulatory blood pressure monitor over the course of
      one workday. Blood pressure averages were calculated at work (11 am to 3 pm),
      home (6 pm to approximately 10 pm), and during sleep (approximately 10 pm to 6
      am). The stressfulness of the work and home microenvironments was rated by self
      report on a scale of 0 (low) to 10 (high). A repeated measures analysis of
      covariance was used to assess the cross-classified effects of perceived stress
      (work stressed [work > home stress; N = 41], home stressed [home > work stress; N
      = 39], and equally stressed [work = home stress; N = 11]) and age group (18.0
      29.9 years, N = 31; 30-39.9 years, N = 34; 40-49.9 years, N = 26) on the blood
      pressure averages with daily environment as a within-subject factor and measures
      of body fat and menstrual phase as covariates. Work-stressed women had higher
      systolic blood pressure at work, home, and during sleep than home-stressed women
      (127 vs 119, P < 0.001; 124 vs 119, P < 0.05, and 111 vs 104, P < 0.005). There
      were similar patterns for diastolic blood pressure. Age showed a U-shaped
      relationship, with women in the 30-39.9 year age range generally having lower
      systolic and diastolic blood pressures at work (P < 0.05), home (P < 0.10), and
      during sleep (P < 0.05) than younger and older age groups. The interaction
      between age group and perceived stress level was not significant, so that the
      variation in blood pressure associated with perceived stress (work stressed, home
      stressed, and equally stressed) was similar in each age group. Although blood
      pressure changes with age, environment-related stress, particularly job-related
      stress, continues to have a significant effect on daily blood pressure variation.
      However, data also indicate that blood pressure measured during the day may not
      necessarily show a linear increase with age.

PMID- 11460874
TI  - Reliability and validity of parental measurements of infant size.
AB  - This study evaluates the reliability and validity of parental measurements of
      infant size, using illustrated instructions and simple measuring tools. Following
      pilot tests, final methods were evaluated on a sample of 28 parents (26 mothers
      and 2 fathers) of infants from 1 to 6 weeks of age. Parents independently
      measured twice the infant's head circumference (HC), mid-upper arm circumference
      (MUAC), abdominal circumference (AC), and recumbent length (RL). Infants were
      also measured twice by a trained observer. Mean parental measures were correlated
      (intraclass R) with the observer criterion measures at the levels of 0.81 for RL,
      0.70 for AC, 0.80 for MUAC, and 0.94 for HC. Relative differences in the means
      for measurements obtained by parents and the trained observer were small, ranging
      from 0.3% for HC and RL, to 3.8% for AC. Intraclass correlations of reliability
      between the two parental measurements ranged from R = 0.84 for MUAC to 0.96 for
      RL. Given the reliability and validity of the results, the methods tested yield
      measurements that are suitable for ranking individuals and for use in group-level
      analyses, and at least in the case of head circumference, for individual-level
      analyses.

PMID- 11460875
TI  - Time-dependent pharmacokinetic interaction between zidovudine and rifampicin
      following oral administration at 10.00 and 22.00 hours.
AB  - Rifampicin, an antitubercular agent, is a known metabolic inducer. Previous
      studies have suggested that rifampicin may interfere with the pharmacokinetics of
      oral zidovudine when the two drugs are co-administered. Circadian variations in
      the pharmacokinetics of rifampicin have been reported. We report here a circadian
      influence on the pharmacokinetics of zidovudine in the presence of rifampicin
      when administered orally in rabbits. Either zidovudine or zidovudine with
      rifampicin was administered orally at 10.00 or 22.00 h to 12 healthy rabbits in a
      randomized cross-over study. Serum zidovudine was estimated by HPLC. A
      significant (p <0.05) lowering of Cmax, (1/2), AUC(0-6h) and MRT was observed
      following zidovudine and rifampicin co-administration compared to zidovudine
      alone at 10.00 h. Accordingly clearance increased to a significant extent.
      However, such an interaction effect was masked following administration at 22.00
      h. The time-dependent influence of rifampicin on the pharmacokinetics of
      zidovudine may be due to time-dependent changes in absorption and elimination of
      rifampicin, thus modifying its induction effect on the levels of UDP glucuronyl
      transferase and cytochrome P-450 content in liver which are responsible for
      metabolism of zidovudine.

PMID- 11460876
TI  - Interspecies scaling: is a priori knowledge of cytochrome p450 isozymes involved
      in drug metabolism helpful in prediction of clearance in humans from animal data?
AB  - The objective of this study was to evaluate whether a priori knowledge of
      cytochrome P450 isozymes involved in drug metabolism coupled with Mahmood' and
      Balian's 'rule of exponents' can be helpful for the prediction of clearance in
      humans using animal data. The clearance of 27 randomly selected drugs metabolized
      by different isozymes were scaled up from the animal data (at least three animal
      species) obtained from the literature. Three methods were utilized to generate
      allometric equations to scale up the clearance values: (i) clearance vs body
      weight (simple allometry); (ii) product of the clearance and maximum life-span
      potential (MLP) vs body weight; and (iii) the product of clearance and brain
      weight vs body weight. The choice of one of the methods was based on the 'rule of
      exponents' as described by Mahmood and Balian. The results of this study indicate
      that the knowledge of a particular isozyme does not provide a guide for the
      failure or success of allometry for the prediction of clearance. There is no
      trend which indicates that the chances of accurate prediction of clearance for a
      given drug are comparatively higher or lower when they are metabolized by a
      particular isozyme.

PMID- 11460877
TI  - 17Beta-estradiol stimulates mineralized bone nodule formation when added
      intermittently to SaOS-2 cells.
AB  - It is now well established that estrogen inhibits bone resorption. However, its
      effect on bone formation remains controversial. We studied the effect of 17beta
      estradiol (E2) on mineralized bone nodule formation in long-term cultures of
      osteosarcoma SaOS-2 cells. We showed that SaOS-2 cells formed mineralized nodules
      which under electron microscopy revealed a bone structure with active
      osteoblasts, entrapped osteocytes, extracellular collagen fibrils and
      hydroxyapatite deposits, making this system a valid model to study bone formation
      in vitro. Intermittent addition of E2 for 6 hours during a 48-hour cycle of
      changes of medium, starting from day 3, resulted in a dose-dependent stimulation
      of mineralized bone nodule number and area, as well as alkaline phosphatase
      activity. In conclusion, we report for the first time a stimulatory effect of E2
      on mineralized bone nodule formation in human osteoblasts in culture.

PMID- 11460878
TI  - A review of xenobiotic metabolism enzymes in Parkinson's disease and motor neuron
      disease.
AB  - The role of xenobiotic metabolising enzymes (XMEs) in disease aetiology has been
      under investigation by numerous researchers around the world for the last two
      decades. The association of a number of defects in both phase I and phase II
      reactions with Parkinson's disease (PD) and motor neuron disease (MND) have been
      extensively studied. This review of the work of the group based initially at the
      University of Birmingham into the functional genomics of XMEs and
      neurodegenerative diseases has indicated that: 1. Sub-groups of patients with PD
      and MND can be identified with problems in xenobiotic metabolism by in vivo or in
      vitro methods. 2. 38-39% of the patients with MND/PD have a defect in the S
      oxidation of the mucoactive drug, carbocysteine, by an unknown cytosolic
      oxidase(s). The odds risk ratio for the association of this defect with these
      diseases was calculated to be 10.21 for MND and 10.50 for PD. 3. Patients with PD
      appear to have an altered substrate specificity for monoamine oxidase B
      substrates in an in vitro platelet assay. 4. Patients with MND have an increased
      capacity to S-methylate aliphatic sulphydryl compounds in an in vivo challenge as
      well as an in vitro erythrocyte thiol methyltransferase assay. The results of
      over a decade of investigations into both PD and MND indicate that these are
      diseases with mutifactorial origins that encompass both genetic predisposition
      and environmental insult.

PMID- 11460879
TI  - Effect of ubidecarenone on warfarin anticoagulation and pharmacokinetics of
      warfarin enantiomers in rats.
AB  - Interaction between the antioxidant ubidecarenone and the oral anticoagulant
      warfarin enantiomers was investigated in rats. The decreased hypoprothrombinemic
      response, assessed by means of percent changes of prothrombin complex activity
      and clotting factor VII activity, to warfarin, was observed following oral
      administration of 1.5 mg/kg racemic warfarin to rats during an 8-day oral regimen
      (10 mg/kg daily) of ubidecarenone. The antioxidant had no apparent effect on the
      in vitro rat serum protein binding of warfarin enantiomers. Treatment with
      ubidecarenone did not affect the absorption and distribution of the S- and R
      enantiomers of warfarin, but produced a significant increase in the total serum
      clearance values of both R- and S-warfarin in rats. This effect was more
      pronounced with R-warfarin than with S-warfarin. The increased clearance values
      are attributable to acceleration of certain metabolic pathways and renal
      excretion of the warfarin enantiomers.

PMID- 11460880
TI  - An enzymatic method for the detection of human serum albumin.
AB  - Albumin is the most abundant protein in human serum. A dye-binding method is
      commonly used in clinical laboratories for its estimation using different types
      of dyes. However, all these dye methods were interfered by a variety of
      compounds. Here we present a method for the detection of albumin in human serum
      and other biological fluids. The principle is based on the fact that lactate
      dehydrogenase isoenzyme-5 (LDH-5) binds specifically to Dextran-Blue (DB).
      Albumin inhibits the binding of LDH-5 with DB. Absence of LDH activity in DB
      fraction after gel filtration indicates the presence of albumin in sample and
      vice versa.

PMID- 11460881
TI  - Homozygous VN (677C to T) and d/D (2756G to A) variants in the
      methylenetetrahydrofolate and methionine synthase genes in a case of
      hyperhomocysteinemia with stroke at young age.
AB  - Hyperhomocysteinemia is known to be associated with an increased risk of
      myocardial infarction, stroke, peripheral arterial disease, and venous
      thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and
      methionine synthase (MS) may account for reduced enzyme activity and
      hyperhomocysteinemia. A recent study has documented evidence of polygenic
      regulation of plasma homocyteine. We report here on a case of occlusive stroke at
      young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the
      MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.

PMID- 11460882
TI  - HNF1 and/or HNF3 may contribute to the tissue specific expression of glucokinase
      gene.
AB  - A possible role of hepatocyte nuclear factor 1 (HNF1) or HNF3, a predominant
      trans-acting factors of hepatic or pancreatic beta-cells, was examined on the
      tissue specific interdependent expression of glucokinase (GK) in liver, H4IIE,
      HepG2, HIT-T15 and MIN6 cell line. The tissues or cell lines known to express GK
      showed abundant levels of HNF1 and HNF3 mRNA as observed in liver, H4IIE, HepG2,
      HIT-T15 and MIN6 cells, whereas they were not detected in brain, heart, NIH 3T3,
      HeLa cells. The promoter of glucokinase contains several HNF3 consensus sequences
      and are well conserved in human, mouse and rat. Transfection of the glucokinase
      promotor linked with luciferase reporter to liver or pancreatic beta cell lines
      showed high interacting activities with HNF1 and HNF3, whereas minimal activities
      were detected in the cells expressing very low levels of HNFs. The binding of
      HNF1 or HNF3 to the GK promoter genes was confirmed by electrophoretic mobility
      shift assay (EMSA). From these data, we propose that the expression of HNF1
      and/or HNF3 may, in part, contribute to the tissue specific expression of GK

PMID- 11460883
TI  - The protective effect of Amomum xanthoides extract against alloxan-induced
      diabetes through the suppression of NFkappaB activation.
AB  - This study was undertaken to investigate the preventive mechanism of Amomum
      xanthoides extract against the development of alloxan-induced diabetics of mice.
      Pretreatment of mice with A. xanthoides extract via intraperitoneum prevented
      alloxan-induced hyperglycemia and hypoinsulinemia in a dose dependent manner.
      Histological examination of pancreatic tissue from A. xanthoides extract treated
      mice showed that the islet cells remain unaffected by alloxan treatment. NFkappaB
      activation in the pancreas 30 min after alloxan injection (60 mg/kg, iv), as
      assessed by an electrophoretic mobility shift assay, was not detected in the mice
      pretreated with A. xanthoides extract. These results suggest that NFkappaB
      activation may be one of the critical determinant in the progression of the
      disease. Considering the preventive effect of A. xanthoides extract from alloxan
      induced diabetics development, these results may provide the possible therapeutic
      value of A. xanthoides extract for the prevention of diabetes mellitus
      progression.

PMID- 11460884
TI  - Production and characterization of monoclonal antibodies against amphiphysins.
AB  - Amphiphysin I and II, proteins enriched in nerve terminals, form heterodimers and
      interact with dynamin and synaptojanin through their Src homology 3 (SH3) domain.
      In order to study the expression profile of Amphs in cells and tissues and the
      interaction state with other cellular molecules, we have prepared specific
      monoclonal antibodies (mAbs) designed to bait N-terminus, middle part, and C
      terminus domains of Amph I, respectively by immunizing with the expressed smaller
      domain molecules using the GST gene fusion system. The expression of Amphs was
      found to be most abundant in PC12 cells, followed by B103 cells and vascular
      smooth muscle cells. Western blot analysis showed a relatively high level
      expression of Amphs that were found in both mouse and rat brain. There appeared
      to be some species difference in the expression pattern, i.e. Amphs are present
      more in the testis than in the lungs in rats, however, they are reversed in mice.
      Characterization of the mAbs revealed that clone 14-23 precipitated Amph I and
      II, whereas clone 8-2 could only precipitate Amph I. In addition, clathrin and
      dynamin in a complex with Amph were captured in the precipitate formed by mAbs
      and identified by the Western blot analysis. Cellular distribution of Amph was
      visualized with confocal immunofluorescence microscopy performed using the
      labeled-mAbs. Taken together, these results demonstrated that mAbs provided an
      excellent measure for studying Amphs' expression profile and their interacting
      proteins.

PMID- 11460885
TI  - Cloning and characterization of 5'-upstream region of human phospholipase C-beta2
      gene.
AB  - 5'-upstream region of the phospholipase C-beta2 gene, 810 bp, was cloned and
      characterized. S1 nuclease mapping and primer extension analyses revealed that a
      single transcriptional start site locates at 284 nucleotides upstream from the
      beginning of translation. The 5-upstream region lacks both TATA motif and typical
      initiator sequence, but retains GC-rich segment. Two putative regulatory regions,
      a negative region (-636/-588) and a positive region (-98/ -13) were identified in
      the upstream region of PLC-beta2 gene. We suggest that the transcription of PLC
      beta2 may be regulated by binding of regulatory proteins to the negative and/or
      positive regulatory regions located in the upstream of the gene.

PMID- 11460886
TI  - A novel method using edge detection for signal extraction from cDNA microarray
      image analysis.
AB  - Gene expression analyses by probes of hybridization from mRNA to cDNA targets
      arrayed on membranes or activated glass surfaces have revolutionized the way of
      profiling mega level gene expression. The main remaining problems however are
      sensitivity of detection, reproducibility and data processing. During processing
      of microarray images, especially irregularities of spot position and shape could
      generate significant errors: small regions of signal spots can be mis-included
      into background area and vice versa. Here we report a novel method to eliminate
      such obstacles by sensing their edges. Application of edge detection technology
      on separating spots from the background decreases the probability of the errors
      and gives more accurate information about the states of spots such as the pixel
      number, degree of fragmentation, width and height of spot, and circumference of
      spot. Such information can be used for the quality control of cDNA microarray
      experiments and filtering of low quality spots. We analyzed the cDNA microarray
      image that contains 10,368 genes using edge detection and compared the result
      with that of conventional method which draws circle around the spot.

PMID- 11460887
TI  - Cell-free expression and functional reconstitution of CALM in clathrin assembly.
AB  - Clathrin-mediated vesicle formation is an essential step in the intracellular
      trafficking of the protein and lipid. Binding of clathrin assembly protein to
      clathrin triskelia induces their assembly into clathrin-coated vesicles (CCVs).
      In order to better understand a possible role of post-translational modification
      of CALM (clathrin assembly protein lymphoid myeloid), the homologue of AP180, in
      the assembly of CCVs, CALM was expressed in the cell-free reticulocyte
      translation system that is capable of carrying out post-translational
      modification. The apparent molecular weight of the expressed recombinant CALM was
      estimated as 105 kD. Alkaline phosphatase treatment of CALM resulted in a
      mobility shift on SDS-PAGE. We found that CALM was associated with the proteins
      harboring SH3 domain, promote assembly of clathrin triskelia into clathrin cage
      and bound to the preformed clathrin cage. CALM was also proteolyzed by caspase 3
      and calpain but not by caspase 8. These results indicated that the post
      translationally modified CALM, expressed in the eukaryotic cell-free reticulocyte
      translation system was able to mediate the assembly of clathrin and the coated
      vesicle formation.

PMID- 11460888
TI  - Potential role of leptin in angiogenesis: leptin induces endothelial cell
      proliferation and expression of matrix metalloproteinases in vivo and in vitro.
AB  - Leptin, the product of ob gene, is an endocrine hormone that regulates adipose
      tissue mass. Recently, leptin has been found to generate a growth signal
      involving a tyrosine kinase-dependent intracellular pathway and promote
      angiogenic processes via activation of leptin receptor (Ob-R) in endothelial
      cells. However, it is not clear how leptin functions to promote multi-step
      processes involved in the neovascularization at the atherosclerotic plaque. We
      have examined the expression of matrix metalloproteinases (MMPs) and tissue
      inhibitors of metalloproteinases (TIMPs) and Ob-R in human atherosclerotic
      lesions, leptin-mediated angiogenesis in vivo and in vitro. Immunohistochemical
      analysis of human atherosclerotic aorta revealed an increased expression of Ob-R
      in the intima of neorevascularized regions and of both MMPs and TIMPs
      predominantly in the endothelial lining of intimal neovessels and
      macrophages/foam cells. In the rat corneal angiogenesis assay, leptin elicited a
      comparable sensitivity of angiogenic activity to those of vascular endothelial
      growth factor (VEGF). The immunohistological analysis of the leptin-treated rat
      cornea showed definitive rises in Ob-R, MMPs and TIMPs expression as well as
      those of VEGF receptor (VEGFR-1). Leptin (10-40 ng/ml) induced proliferation of
      the human umbilical vein endothelial cells (HUVECs) and elevation of MMP-2, MMP
      9, TIMP-1, and TIMP-2 expression in a dose-dependent manner. Leptin also induced
      increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery
      smooth muscle cells (HCASMCs). These findings suggest that leptin, a hormone with
      pluralistic properties including a mitogenic activity on vascular endothelial
      cells, plays a role in matrix remodeling by regulating the expression of MMPs and
      TIMPs. Taken together, our findings further provide evidences for leptin's role
      as an angiogenesis inducer in the normal organ (rat cornea) and in aberrant
      vasculature under duress like atherosclerosis.

PMID- 11460889
TI  - Clinically significant drug interactions with agents specific for migraine
      attacks.
AB  - The drugs which provide specific relief from migraine attacks, the ergopeptides
      (ergotamine and dihydroergotamine) and the various 'triptans' (notably
      sumatriptan), are often prescribed for persons already taking various migraine
      preventative agents, and sometimes drugs for other indications. As a result,
      migraine-specific drugs may become involved in drug-drug interactions. The
      migraine-specific drugs all act as agonists at certain subclasses of serotonin (5
      hydroxytryptamine; 5-HT) receptor, particularly those of the 5-HT1D subtype, and
      produce vasoconstriction through these receptor-mediated mechanisms. The oral
      bioavailabilities of these drugs, particularly those of the ergopeptides, are
      often incomplete, due to extensive presystemic metabolism. As a result, if
      migraine-specific agents are coadministered with drugs with vasoconstrictive
      properties, or with drugs which inhibit the metabolism of the migraine-specific
      agents, there is a risk of interactions occurring which produce manifestations of
      excessive vasoconstriction. This can also occur through pharmacodynamic
      mechanisms, as when ergopeptides or triptans are coadministered with methysergide
      or propranolol (although a pharmacokinetic element may apply in relation to the
      latter interaction), or if one migraine-specific agent is used shortly after
      another. When ergopeptide metabolism is inhibited by the presence of macrolide
      antibacterials, particularly troleandomycin and erythromycin, the resultant
      interaction can produce ergotism, sometimes leading to gangrene. Similar
      pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably
      apply to combination of the ergopeptides with HIV protease inhibitors (indinavir
      and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan
      metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise
      circulating triptan concentrations, although this does not yet seem to have led
      to reported clinical problems. Caffeine may cause increased plasma ergotamine
      concentrations through an as yet inadequately defined pharmacokinetic
      interaction. However, a direct antimigraine effect of caffeine may contribute to
      the claimed increased efficacy of ergotamine-caffeine combinations in relieving
      migraine attacks. Serotonin syndromes have been reported as probable
      pharmacodynamic consequences of the use of ergots or triptans in persons taking
      serotonin reuptake inhibitors. There have been two reports of involuntary
      movement disorders when sumatriptan has been used by patients already taking
      loxapine. Nearly all the clinically important interactions between the
      ergopeptide antimigraine agents and currently marketed drugs are likely to have
      already come to notice. In contrast, new interactions involving the triptans are
      likely to be recognised as additional members of this family of drugs, with their
      different patterns of metabolism and pharmacokinetics, are marketed.

PMID- 11460890
TI  - Aetiopathogenesis and pathophysiology of bulimia nervosa: biological bases and
      implications for treatment.
AB  - Bulimia nervosa is an eating disorder characterised by recurrent episodes of
      binge eating and associated efforts to purge the ingested calories through self
      induced vomiting, laxative or diuretic abuse, fasting or intensive exercise. The
      aetiopathogenesis and pathophysiology of the disorder are currently unclear.
      Biological bases have been proposed repeatedly, based on several lines of
      evidence: hunger, satiety and food choice are regulated by neurotransmitters and
      neuropeptides, and impairment of eating habits may be related to alterations in
      the secretion of these chemicals; genetic studies suggest that these
      neurotransmitter systems are dysfunctional in individuals with bulimia nervosa;
      and the frequent comorbidity of bulimia nervosa with major depressive and
      obsessive-compulsive disorders, conditions in which multiple alterations of brain
      biochemical functions have been demonstrated. Data in the literature suggest that
      levels of noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5
      HT) are lower in individuals with bulimia nervosa than in healthy controls.
      Levels of dopamine are similar to, or lower than, those in controls. After
      remission of the disorder, noradrenergic function returns to that seen in
      controls, whereas dopaminergic and serotonergic function rebound to levels higher
      than in controls. Among the neuropeptides, alterations in the levels of
      neuropeptide Y, peptide YY, beta-endorphin, corticotrophin-releasing hormone,
      somatostatin, cholecystokinin and vasopressin have been found in the symptomatic
      phase of bulimia nervosa, with a return to levels seen in controls after
      remission. Pharmacological treatment of bulimia nervosa that is directed at
      correction of the neurochemical alterations observed is difficult because of the
      complexity of the impairments. However, such treatment is necessary and should be
      continued long after symptomatic remission to ensure reinstitution of cerebral
      biochemical homeostasis.

PMID- 11460891
TI  - Oxcarbazepine: an update of its efficacy in the management of epilepsy.
AB  - Oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) is a 10
      keto analogue of carbamazepine with anticonvulsant activity. In newly diagnosed
      adult patients, oxcarbazepine monotherapy is as effective as phenytoin and
      vaiproic acid at reducing generalised tonic-clonic and partial seizure frequency.
      Furthermore, oxcarbazepine 2400 mg/day as monotherapy has also proved effective
      in the treatment of refractory partial seizures in adult patients. Oxcarbazepine
      600, 1200 and 2400 mg/day as adjunctive therapy significantly reduced seizure
      frequency compared with placebo in 692 patients with refractory partial seizures.
      The efficacy of oxcarbazepine monotherapy is similar to that of phenytoin in the
      treatment of children and adolescents with newly diagnosed partial or generalised
      tonic-clonic seizures. Additionally, adjunctive therapy with oxcarbazepine was
      significantly more effective than placebo at reducing seizure frequency in
      children and adolescents with refractory partial seizures. The most commonly
      reported adverse events associated with oxcarbazepine monotherapy and/or
      adjunctive therapy in adults and/or children are somnolence, dizziness, headache,
      nausea and vomiting. Oxcarbazepine monotherapy is better tolerated than phenytoin
      (in both adults and children) and valproic acid (in adults), and although 75 to
      90% of adult patients in 5 recent monotherapy studies reported adverse events
      while receiving oxcarbazepine, <8% withdrew from treatment because of them. Acute
      hyponatraemia, although usually asymptomatic, develops in 2.7% of patients
      treated with oxcarbazepine. Adverse events most likely to resolve upon switching
      to oxcarbazepine therapy from treatment with carbamazepine are undetermined skin
      reactions (rashes, pruritus, eczema), allergic reactions and a combination of
      malaise, dizziness and headache. Although oxcarbazepine does have a clinically
      significant interaction with some drugs (e.g. phenytoin and oral contraceptives),
      it has a lower propensity for interactions than older antiepileptic drugs (AEDs)
      because its major metabolic pathway is mediated by noninducible enzymes.
      CONCLUSION: Oxcarbazepine as monotherapy is a viable alternative to established
      AEDs in the treatment of partial and generalised tonic-clonic seizures in adults
      and children. Furthermore, it is also effective as adjunctive therapy in the
      treatment of refractory partial seizures in both age groups. In addition, the
      drug is tolerated better than the older, established AEDs, and has a lower
      potential for drug interactions. These attributes make oxcarbazepine an effective
      component in the initial treatment of newly diagnosed partial and generalised
      tonic-clonic seizures, and also as an adjunct for medically intractable partial
      seizures in both adults and children.

PMID- 11460892
TI  - Do cholinesterase inhibitors have disease-modifying effects in Alzheimer's
      disease?
AB  - During the last decade, a systematic effort to develop a pharmacological
      treatment for Alzheimer disease (AD) has resulted in drugs being registered for
      the first time in the US and Europe for this specific indication. The 3 agents
      registered are cholinesterase inhibitors (ChEIs). The major therapeutic effect of
      ChEIs in patients with AD is the maintenance of cognitive function, as compared
      with placebo, during a 6-month to 1-year period of treatment. Additional drug
      effects that may occur are the slowing of cognitive deterioration and improvement
      of behaviour and daily living activities. Comparison of clinical effects of 6
      ChEIs demonstrates a rather similar magnitude of improvement in cognitive outcome
      measures. For some drugs, this level may represent an upper limit, while for
      others it may be possible to increase the benefit further. In order to maximise
      and prolong positive drug effects it is important to start treatment early and
      adjust the dosage during treatment. Recent studies that used this administration
      strategy have shown that in many patients, the stabilisation effect produced by
      ChEIs can be prolonged for as long as 36 months. This long-lasting effect
      suggests mechanisms of action other than symptomatic ones. In this article, the
      effects of ChEIs on beta-amyloid metabolism are postulated to explain the
      stabilising (i.e. disease-modifying) effects of the drugs. Evidence for such a
      mechanism is available at the experimental but not yet at the clinical level.

PMID- 11460893
TI  - Separation anxiety disorder in children and adolescents: epidemiology, diagnosis
      and management.
AB  - This paper provides an overview of the phenomenology, longitudinal outcome data,
      assessment and management of separation anxiety disorder (SAD) in children and
      adolescents. SAD is qualitatively different from early worries, and is
      characterised by an abnormal reactivity to real or imagined separation from
      attachment figures, which significantly interferes with daily activities and
      developmental tasks. Different epidemiological studies indicate a prevalence of 4
      to 5% in children and adolescents. In contrast to other anxiety disorders, 50 to
      75% of children with SAD come from homes of low socioeconomic status. The
      severity of symptomatology ranges from anticipatory uneasiness to full-blown
      anxiety about separation, but children are usually brought to the clinician when
      SAD results in school refusal or somatic symptoms. School refusal is reported in
      about 75% of children with SAD, and SAD is reported to occur in up to 80% of
      children with school refusal. Longitudinal studies have suggested that childhood
      SAD may be a risk factor for other anxiety disorders, but whether this link is
      specific to, for example, panic disorder and agoraphobia, or whether SAD
      represents a general factor of vulnerability for a broad range of anxiety
      disorders is still debated. Most relevant data are reported on nonpharmacological
      treatments (psychoeducational, behavioural, cognitive-behavioural, family and
      psychodynamic), and these are the first choice approach in SAD. Controlled
      studies show efficacy of cognitive-behavioural therapy in children with anxiety
      disorders and specifically in SAD-school phobia, supporting this approach as the
      best proven treatment. Pharmacotherapy should be used in addition to behavioural
      or psychotherapeutic intervention when the child's symptoms have failed to
      respond to those treatments, and he/she is significantly impaired by the
      symptoms. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors
      (SSRI) have a good adverse effect profile and may be considered as first choice
      drugs in SAD. When different SSRIs fail to improve symptomatology, a trial with a
      tricyclic antidepressant (TCA) is indicated, with careful monitoring of cardiac
      functioning. Because of the adverse effect profile and the potential for abuse
      and dependence, benzodiazepines should be used only when a rapid reduction of
      symptomatology is needed, until the SSRI or the TCA have begun to be effective
      (few weeks). Buspirone should be considered in children who have not responded to
      other treatments. Further research is needed to confirm efficacy of newer
      antidepressants (venlafaxine, mirtazapine, nefazodone) in childhood anxiety
      disorders.

PMID- 11460894
TI  - Leukocyte arylsulfatase A activity in patients with alcohol-related cirrhosis.
AB  - Arylsulfatase (ASA) enzyme deficiency is associated with metachromatic
      leukodystrophy (MLD), which is a hereditary myelin metabolic disease. It has been
      proposed that in alcoholic subjects with abnormal ASA, the accumulation of
      sulfatides may lead to demyelinization and generalized cerebral atrophy. ASA may
      be diminished in subjects with alcoholic cirrhosis having encephalopathic
      manifestations. This idea has not been previously proposed. Leukocyte
      arylsulfatase A (ASA) activity was measured in 30 healthy male volunteers and 28
      patients with alcohol-related cirrhosis. The patients were divided into two
      groups: patients with alcohol-related cirrhosis with hepatic encephalopathy
      history and patients with alcoholic cirrhosis without history of hepatic
      encephalopathy. Alcoholic cirrhotic patients with history of encephalopathy
      showed 58.21% (40.95 nmol/mg protein/h) less enzymatic activity than a control
      group (98.00 nmol/mg protein/h), whereas the group without history of
      encephalopathy showed an ASA value which was 38.2% (60.55 nmol/mg protein/h) less
      than the control group. The results suggest that the low ASA activity is a factor
      associated to the appearance of encephalopathy in patients with alcohol-related
      cirrhosis.

PMID- 11460895
TI  - A comparison of anthropometric indices of nutritional status in Tukanoan and
      Achuar Amerindians.
AB  - Anthropometric data from a Tukanoan population in the Vaupes region of Colombia
      and an Achuar population in the Ecuadorian Amazon were compared relative to
      international references. The Tukanoans exploit an oligotrophic blackwater
      ecosystem, whereas the Achuar inhabit a resource rich montane ecosystem. Given
      this ecological distinction, three hypotheses regarding nutritional statuses were
      proposed: (1) Tukanoans are significantly shorter than the Achuar, indicating a
      greater degree of stunting; (2) Tukanoans are significantly leaner, indicating a
      greater degree of wasting; and (3) Tukanaons have significantly lower upper arm
      muscle area, indicating lower lean body mass. Z-scores for height, weight-for
      height, and estimated upper arm muscle area were determined and significant
      nutritional stress was assumed at z < or = -2.0. Between population differences
      in z-scores for height-for-age (ZHT), weight-for-height (ZWH), and upper arm
      muscle area (ZUMA) were examined using analysis of variance with a subsequent
      Scheffe's test. Between-group differences in the frequencies of individuals with
      low z-scores (z < or = -2.0) were assessed via chi-squared analysis. Both
      populations showed stunting in most age groups, but neither showed low ZWH or
      ZUMA. Significant differences between populations were found only for ZHT in
      children (females 1.0-4.9 and 5.0-9.9 years, and males 5.0-9.9 years). Tukanoans
      have significantly higher frequencies of stunting in all age-sex groups except
      females and males age 30-49.9 years. There were no significant between-population
      differences in the frequencies of individuals with low ZWH or ZUMA. These
      differences in nutritional status may reflect differences in resource
      availability.

PMID- 11460896
TI  - A comparison of physical activity levels in two contrasting elderly populations
      in Thailand.
AB  - There is little information available on physical activity patterns in the
      elderly in developing countries. This is particularly important at a time when
      developing countries are in transition and show signs of moving toward Western
      style patterns of physical activity and social structure. This study is unique in
      that it compares the physical activity levels in two contrasting communities: a
      residential home and a rural community of elderly subjects in Thailand. Ninety
      elderly people living in a residential home and 78 elderly people living with
      their families in a rural community were recruited. The men in the rural
      community were slightly lighter and leaner than the men in the residential
      community, but the differences were not significant. However, the women were
      significantly (P < 0.001) heavier and fatter in the residential home than in the
      rural community. This is consistent with the higher levels of physical activity
      in the rural community. There was considerable variation in physical activity in
      this population. The physical activity level (PAL) values ranged from 1.21 to
      1.73 in the residential home and from 1.21 to 3.08 in the rural community. This
      is apparently the first study of physical activity patterns in elderly subjects
      in a developing country. It highlights the variation in activity within the rural
      community and between both communities. The opportunities for the elderly living
      in the residential home to have active lifestyles are limited. It is likely that
      this will result in increased morbidity in the final years of life.

PMID- 11460897
TI  - Prediction of adult stature for Japanese population: a stepwise regression
      approach.
AB  - The longitudinal growth in stature for 509 males and 311 females was
      characterized from early childhood to adulthood. A triphasic generalized logistic
      (BTT) model (Bock et al. [1994] Chicago: SSI) was used through the AUXAL software
      program. Growth parameters were derived from the estimated distance and velocity
      curves for each individual. A set of estimated growth parameters, including adult
      stature, was selected to develop equations, through the forward stepwise
      regression method, for the prediction of adult stature for Japanese boys and
      girls.

PMID- 11460898
TI  - Growth of children in two economically diverse Peruvian high-altitude
      communities.
AB  - The growth of children living in two high-altitude communities associated with an
      active copper mine in southern Peru was examined. In the community directly
      associated with mining operations, nutritional and health conditions were
      believed to be relatively favorable as a result of the substantial mine-related
      infrastructure that had developed over the previous 12 years. In contrast, few
      such benefits were available in the other community, which provides limited part
      time labor at the mine. Anthropometric data, including measurements of height,
      weight, skinfold thicknesses, upper arm circumference, and chest dimensions, and
      determination of bone age, were collected from a total of 880 children between
      the ages of 4 and 18 years. There were significant differences between the two
      communities, with those in the mining community exhibiting significantly greater
      height and weight, a higher level of body fat, and more rapid skeletal
      development. Among children over the age of 12 years, a plateau in height was
      seen, suggesting that the benefits to growth resulting from mining-related
      development were more noticeable in younger children. Compared with Peruvian high
      altitude populations examined during the 1960s, both samples from the present
      study were substantially taller and heavier, suggesting that despite local
      differences in socioeconomic conditions between the communities studied, overall
      conditions for growth are generally more favorable than those that existed among
      Peruvian high-altitude populations surveyed in the 1960s.

PMID- 11460899
TI  - Variation in sexual dimorphism in relation to physical activity.
AB  - The aim of this study was to examine variations in sexual dimorphism in relation
      to physical activity. A sample of 542 males and females (20-30 years), born and
      resident in Cagliari (Sardinia, Italy), was divided into two groups: active and
      inactive. Twenty-five anthropometric dimensions were taken (weight, lengths,
      breadths, circumferences, and skinfolds). The circumferences and skinfolds were
      adjusted for the effects of overall body size (represented by skeletal
      variables). Body composition parameters--fat-free mass (FFM), fat mass (FM), and
      arm muscular area (AMA)--were derived from the adjusted values. The D index
      (Bennett, 1981; Chakraborty and Majumder, 1982) was used to assess the degree of
      sexual dimorphism. The difference between the D values of active and inactive
      individuals was analyzed with the technique of Bennett (1981). Principal
      components analysis (PCA) was performed on groups of homogeneous variables
      (circumferences and skinfolds) in order to simplify the description of the
      original anthropometric data. The univariate and multivariate analyses indicate a
      greater sex difference in the group of individuals who are regularly active. The
      results agree with theoretical expectations, and suggest greater stability of
      women to environmental pressures (i.e., physical activity).

PMID- 11460900
TI  - Changes in adiposity and body mass index from late childhood to adult life in the
      Trois-Rivieres study.
AB  - This study explored tracking of the body mass index (BMI) in a representative
      subgroup of subjects (95 women and 96 men) who were involved in the Trois
      Rivieres Growth and Development Study by testing autocorrelations between data
      for 10, 11, and 12 years and corresponding values at 34 years of age. Tracking of
      skinfold measurements (subscapular, triceps, suprailiac, and abdominal, and their
      sum) over the same intervals (60 women and 52 men) was also evaluated. After the
      age of 12 years, subjects showed a similar development of absolute values,
      whether they were from the experimental or the control group. Gains of the BMI
      and skinfold thicknesses showed expected gender differences. In particular, men
      showed larger gains of the BMI and abdominal skinfolds, whereas women had larger
      gains in the triceps skinfold. Increases in the sum of four skinfolds did not
      differ significantly between men and women, suggesting that the larger BMI gains
      in men were caused by a larger relative increase of fat-free mass in the men.
      Tracking coefficients for the BMI were lower in men than in women between 10, 11,
      12, and 34 years (r = 0.43-0.49 vs. r = 0.64-0.70, P < 0.001). The results
      indicate that the body composition of participants in the Trois-Rivieres Growth
      and Development study developed in a similar fashion whether or not their primary
      school instruction included additional physical education instruction. The
      results also suggest that prediction of adult obesity based on childhood BMI
      measurements is more effective in girls than in boys.

PMID- 11460901
TI  - Longitudinal growth study of male Japanese junior high school athletes.
AB  - The aim of this study was to establish the pattern of adolescent growth in height
      of male Japanese athletes, and to compare their growth with appropriate controls.
      The sample consisted of 126 baseball, 39 basketball, 83 soccer, and 53 volleyball
      players, and 36 nonathletes. The data were collected retrospectively in six
      public schools in Fukui Prefecture of Western Japan between 1970 and 1987. All
      subjects were measured at yearly intervals between the age of 6 and 18 years. The
      total number of measurement occasions for the 337 subjects amounted to 4,134.
      Athletes trained between 13 and 18 h/week. Individual growth patterns were
      determined by fitting Preece Baines model I to each individual's serial data.
      Various biological parameters were derived from the fitted curves. The results
      indicated that the average growth pattern of these adolescent athletes did not
      differ substantially from the control group. Volleyball players were
      significantly taller at 18 years (+3 cm) than the nonathletes (Student's t-test,
      P < 0.05). Soccer players showed a slight tendency towards late maturation with
      age at take-off and at peak velocity about half a year later than in nonathletes
      (Student's t-test, P < 0.05). The 2.3 cm gain in body height due to the later
      onset of the pubertal growth spurt in soccer players was counterbalanced by a 0.7
      cm smaller prepubertal height and a 0.9 cm smaller adolescent gain, so that they
      ended up slightly, but not significantly, taller than the controls (+0.7 cm). The
      small differences in growth pattern observed between the nonathletes and the
      various sports suggest that, in contrast with top-level athletes, body size and
      maturation rate were not important selective factors in the various groups of
      athletes of the present study.

PMID- 11460902
TI  - Do "helpers at the nest" increase their parents' reproductive success?
AB  - "Helpers at the nest," usually offspring of a preceding litter who contribute by
      feeding the young to increase the reproductive success of a breeding pair, are
      known in many species of birds and mammals. Although similar behaviors were
      described by ethnological observations in several human societies, there is a
      lack of data on their existence and role. This study of 794 reproductive life
      histories of post-menopausal Berber women of Southern Morocco aims to provide
      such information. Results show that the presence of "probable helpers" in the
      household is related to higher fertility scores and is associated with improved
      survival of offspring to sexual maturity. In contrast to sparse observations from
      other human societies, there is no indication that child caretaking would be
      specific to eldest daughters. Although the association between offspring survival
      and helping patterns seems highly probable, there is no confirmation that child
      caretaking per se is the relevant variable. Contrary to nonhuman helpers at the
      nest, workloads of children range from housekeeping to light agricultural tasks,
      and are not focused on assisting younger siblings. The improvement of
      reproductive success is probably the result of multiple interactions, among which
      the network of kinship would play a role at both the levels of economy and
      reciprocal assistance.

PMID- 11460903
TI  - Genetic population history relationships of the population of Bogota, Colombia,
      by using the D1S80, VWA, and TH01 molecular markers.
AB  - The genetic relationships of the population of Bogota, Colombia, was
      comparatively studied with regard to other populations from America, Europe, and
      Asia, by using the D1S80, VWA, and TH01 molecular loci. From a population history
      point of view, the population of Bogota seems to be more related to a European
      origin, with several differential contributions coming from Amerindians rather
      than from African and Asian populations, when the D1S80 and TH01 markers were
      employed. However, the contribution was greater from African populations for the
      VWA marker. Several explanations are offered to resolve the genetic affiliation
      of this population.

PMID- 11460904
TI  - Physical activity at 9-12 months and fatness at 2 years of age.
AB  - Previous research has shown that physical activity in early infancy does not
      predict later fatness, whereas in preschool children, such a relationship is
      found. The objective of this study was to investigate whether total energy
      expenditure (TEE) and behavior in late infancy are related to subcutaneous and
      total fatness in early childhood. Twenty-six infants were studied at 9-12 months
      and followed up at 2 years of age. Anthropometry, body composition, TEE, and
      behavior were measured in late infancy; skinfold thicknesses and total body fat
      were measured at 2 years of age. Infant TEE adjusted for fat-free mass was not
      related to later fatness. Infant behavior was related to later subcutaneous
      fatness, but not to total body fatness. Lower levels of infant activity were
      associated with greater skinfold thicknesses in childhood. Thus, by late infancy,
      physical activity level is related to subsequent skinfold thickness. Particular
      aspects of infant behavior appear to be more important than the sum of energy
      expended on activity. However, the relationship did not extend to total body fat.

PMID- 11460905
TI  - Adolescent growth events in eight decades of Japanese cohort data: sex
      differences.
AB  - The presence of secular trends in sex differences for the onset or takeoff of the
      adolescent growth spurt and subsequent (adolescent) growth of Japanese boys and
      girls were investigated using data published in "The Statistical Report of the
      School Health Survey" of the Ministry of Education, Science, Sports and Culture,
      Japan. An optimum kernel regression method was used to derive the biological
      parameters of the adolescent growth curve. The six parameters derived from the
      regression analysis were age at takeoff (ATO), height at takeoff (HTO), velocity
      at takeoff (VTO), peak height velocity (PHV), age at PHV (APHV), and height at
      PHV (HPHV). The sex difference in age at PHV is about 2.1 years. The sex
      difference in age at takeoff was about 2.1 years starting with the birth year of
      1943, but has become almost insignificant with the birth year of 1980. After
      1960, the sex difference in mean HPHV varied within 12-13 cm, but the difference
      in HTO showed a decreasing trend. After the birth year of 1911, the rate of
      growth at HTO for girls has become markedly greater than for boys. In contrast,
      the rate of growth at HPHV for girls has become significantly smaller than for
      boys (P < 0.05). Sex differences in ATO, HTO and VTO were significantly and
      negatively correlated with differences in APHV and HPHV, but positively
      correlated with the difference in PHV. The sex difference in PHV had no
      relationship with the differences in APHV and HPHV.

PMID- 11460906
TI  - Evidence on major gene control of cortical index in pedigree data from Middle
      Dalmatia, Croatia.
AB  - It was recently reported that the inheritance of the metacarpal cortical index
      (CI) in the Chuvashian population can be described in terms of a major gene (MG)
      model. By applying transmission probability tests, the hypothesis was accepted
      that not only baseline level of CI but also its sex-specific dependence on age
      were under control of the same putative large-effect gene. Using a pedigree
      sample from the population of the islands of Middle Dalmatia, Croatia (847
      observed individuals in 278 pedigrees), data are presented to support the above
      findings. The following hypotheses were accepted: (i) inheritance of baseline CI
      in the Croatian population can be attributed to the effect of a MG responsible
      for about 42% of the variation; (ii) the same MG takes part in the control of the
      dependence of CI on age, particularly the age at onset of involutive bone changes
      (inflection point), and of the rate of decrease in CI with age (slope
      coefficient). Issues related to the assortative mating effect on CI and the
      determination of the most parsimonious model are discussed.

PMID- 11460907
TI  - Age of pubertal onset affects the intensity and duration of pubertal growth peak
      but not final height.
AB  - This paper analyzed the intensity and duration of height growth during puberty in
      boys and girls in relation to rhythm of maturation. A longitudinal clinical
      follow-up between ages of 10 and 20 years, was carried out in a sample of 251
      children grouped according to age at pubertal onset: boys (genital stage 2) at
      the ages of 11 (n = 28), 12 (n = 38), 13 (n = 42), and 14 (n = 27); and girls
      (breast stage 2) at the ages of 10 (n = 37), 11 (n = 47), 12 (n = 19), and 13 (n
      = 13). Height was measured annually. Testicular volume and genital development
      were assessed in boys, and breast development was assessed in girls. There were
      significant differences (P < 0.001) in height at the age of pubertal onset among
      maturity groups. Late maturers were taller than early maturers (r = 0.49, P <
      0.001 for girls; r = 0.38, P < 0.001 for boys). However, final heights did not
      differ according to age of onset in either sex. In boys, later onset of puberty
      was associated with a smaller pubertal height gain (r = -0.60, P < 0.001) and a
      shorter period of pubertal growth (r = -0.61, P < 0.001). Equally in girls,
      earlier onset of puberty was associated with a greater pubertal height gain (r = 
      0.68, P < 0.001) and a longer period of pubertal growth (r = -0.59, P < 0.001).
      In conclusion, age of pubertal onset does not affect final height attained in
      both sexes, since there is an inverse compensatory phenomenon in both sexes
      between height at pubertal onset and the intensity and duration of pubertal
      growth.

PMID- 11460908
TI  - Birth weight and parental PGM1 alleles.
AB  - A deviation of the maternal-neonatal joint phosphoglucomutase locus 1 (PGM1)
      distribution from Hardy-Weinberg expectation has been reported. It was suggested
      that selection on PGM1 during intrauterine life might account for these
      deviations and that maternal and paternal PGM1 alleles might have different
      associations with intrauterine survival. This study considered possible
      associations between the joint mother-newborn PGM1 genotype and intrauterine
      growth. There was a significant association between birth weight percentile class
      and mother-newborn PGM1 genotype in infant females. Also, the paternal PGM1*2
      allele was associated negatively with macrosomia, and this effect was significant
      only in female infants.

PMID- 11460909
TI  - Tumour surgery of the upper cervical spine--a retrospective study of 13 cases.
AB  - A series of tumour cases of the upper cervical spine who we had treated was
      analysed retrospectively with respect to surgical complications, quality of life
      and survival, 13 patients (mean age 56 years, metastases 6, plasmocytomas 3,
      chordomas 2, histiocytosis 1, aneurysmal bone cyst 1) with tumours of the upper
      cervical spine (C2 n = 7, C2 and C3 n = 4, C3 n = 2) were treated during an 8
      year period. A total of 16 operations were carried out with ten one-step
      procedures and three two step-procedures. Eight extra-oral, one transoral, three
      dorsal and, in one case, a combined dorsal and extra-oral tumour removal were
      performed. Four dorsal stabilisation's, four ventral platings and two combined
      ventral platings plus dorsal fixations and eight vertebral body replacements were
      carried out. The neurological status and the quality of life were analysed
      preoperatively and during the follow-up examinations. Flexionextension
      radiographs were taken during follow-up. There was no operative mortality. The
      transient morbidity was 8%. The operative intervention significantly improved the
      quality of life in all patients during the follow-up visits (mean: 20 months). No
      instability was seen. The average survival time of all patients was 23 months.
      Six patients died following the operation after a mean time of 28 (4-64) months.
      Tumour removal in the upper cervical spine using individually modified surgical
      strategies based on an approach combining tumour location, stabilisation and
      vertebral body replacement significantly increases the time of survival and
      quality of life with an acceptable surgical risk for complications.

PMID- 11460910
TI  - Diagnostic and therapeutic management of spinal arachnoid cysts.
AB  - BACKGROUND: The wide variety of intraspinal cystic lesions necessitates different
      elaborate diagnostic procedures to choose the right therapeutic management in
      symptomatic patients. Based on the case reports of seven patients with
      symptomatic spinal arachnoid cysts we discuss the aetiology, diagnostic
      procedures and therapeutic management of extra- and intradural spinal cysts.
      METHOD: All patients underwent MRI, Myelography and CT-Myelography during
      diagnostic evaluation. During surgery the cyst was resected and the communication
      between the cyst and the subarachnoid space was closed. FINDINGS: Two patients
      were identified with intradural, five with extradural spinal arachnoid cysts.
      Postoperative outcome was favourable in those patients without preoperative cord
      damage. INTERPRETATION: MRI is the diagnostic procedure of first choice because
      of its potential to demonstrate the exact localisation, extent and relationship
      of the arachnoid cyst to the spinal cord. Cord atrophy secondary to compression
      can be visualised and used for prediction of neurological outcome. Myelography
      and CT-Myelography (CTM) are still of diagnostic value since they might
      demonstrate the communication between the subarachnoid space and the cyst, which
      is important for surgical planning. The aim of surgical treatment is neural
      decompression and prevention of refilling of the cyst which is best accomplished
      by complete resection of the cyst and closure of the communication between cyst
      and subarachnoid space.

PMID- 11460911
TI  - Biodegradable implants in neurosurgery.
AB  - BACKGROUND: Biodegradable materials have been used for osteosynthesis by
      orthopedic surgeons and craniomaxillofacial surgeons for many years. However,
      such materials are not yet widely used by neurosurgeons despite potential
      applications. This prospective study was undertaken to evaluate potential
      applications of biodegradable materials in neurosurgical interventions. METHODS:
      A total of 104 4-hole plates and 228 screws consisting of copolymer of poly-70
      L/30 D,L-lactide were inserted for fixation of bone flaps in 8 patients and for
      reinsertion of laminoplasties at 28 levels in 16. The craniotomies were performed
      for removal of a brain tumour in 4 cases, for surgical management of an aneurysm
      or cerebral AVM in 2, and for treatment of craniocerebral trauma in another 2.
      Laminoplasties were performed at 25 levels for intraspinal hemangioblastomas in
      15 patients. One patient with an ependymoma underwent 3-level laminoplasty.
      FINDINGS: One patient with severe head injury in whom the bone flap was re
      implanted several months following the craniectomy, developed an aseptic necrosis
      of the bone flap, which had to be removed. Implant rejection was not observed.
      One patient suffered from mild local pain in the area of a biodegradeable screw
      in the frontal region following removal of a sphenoid wing meningeoma. None of
      the patients with laminoplasty showed signs of functional instability or spinal
      cord compression. Implant rejection was not observed. No delayed healing or
      infection occurred. Healing was not delayed and no infections occurred.
      INTERPRETATION: The results encourage further use of biodegradable materials for
      the described applications. Additional studies will be performed to investigate
      the usefulness of biodegradable devices in neurosurgery and to obtain long-term
      results.

PMID- 11460912
TI  - Can 3D-CTA surpass DSA in diagnosis of cerebral aneurysm?
AB  - After introducing of Helical scanning CT (HCT) and 3D-CTA (three-dimensional CT
      angiography), various improvements to these methods have been made every year to
      achieve better imaging quality. The current resolution permits visualisation of
      the internal structure of tumors, although as yet insufficiently clearly. We
      suggest that these improvements can be more efficient than conventional cerebral
      aneurysms angiography. In this study, we compared HCT and 3D-CTA with
      conventional cerebral angiography in patients with cerebral aneurysms at our
      facility. We also examined whether 3D-CTA has the possibility of independent
      clinical application and can surpass conventional DSA in diagnostic efficacy. In
      this paper, we found this information insufficient in clipping operations using
      3D-CTA only when 1) It was difficult to distinguish a crooked infundibular
      dilation from an aneurysm, 2) Imaging threshold influenced the measured value of
      the vascular diameter and 3) It was also difficult to confirm whether the
      peripheral vessels adhere to the aneurysm. In conclusion, from the result of the
      comparison between 3D-CTA and DSA in this study, it was concluded that 3D-CTA is
      a reliable alternative method to conventional angiography in the diagnosis of
      anterior circulation and most aneurysms of regular size. In such cases it may be
      possible to obtain the same quality of preoperative information, but it is less
      invasive.

PMID- 11460913
TI  - Intra-Operative electromyographic monitoring of extra-ocular motor nerves (Nn.
      III, VI) in skull base surgery.
AB  - BACKGROUND: Extraocular motor nerves (Nn. III, IV, VI) are at risk of damage
      during skull base surgery. A new recording technique was employed in 18 patients
      suffering from various skull base tumours in order to extend intra-operative EMG
      monitoring to the extra-ocular muscles. METHODS: Selective intra-operative EMG
      recordings were obtained from extra-ocular muscles by placement of single-shafted
      bipolar needle electrodes under the guidance of B-mode ultrasound to visualise
      the needle tip within the target muscle in the orbital cavity. FINDINGS:
      Following bipolar electrical stimulation, the oculomotor nerve (N.III) was intra
      operatively identified in 5 out of 7 cases, and the abducens nerve (N.VI) in 12
      out of 18 cases. Postoperative (3-6 months) oculomotor nerve function remained
      unchanged in 5 and improved in 2 patients. No permanent deterioration was
      observed. Abducens nerve function deteriorated in two patients and improved in
      one case, but remained unchanged in 15 cases. No side effects occurred. There was
      neither any distinct relation of ocular motor nerve function to the kind and
      extent of SMA ("spontaneous muscle activity") patterns, nor could such
      relationship be detected with concern to neurophysiological parameters
      (latencies, amplitudes) of electrically evoked CMAP ("compound muscle action
      potentials"). INTERPRETATION: The EMG technique proposed proved to be mainly
      effective as a mapping tool for intra-operative localisation and identification
      of ocular motor nerves in skull base surgery. However, the predictive value of
      conventional neurophysiological parameters for clinical outcome, seems to be
      rather poor. Further studies on a larger number of patients are therefore
      required to develop new quantification techniques which enable an intra-operative
      prediction of ocular motor nerve deficits. Further efforts are also necessary to
      extend this technique to the trochlear nerve.

PMID- 11460914
TI  - Classification of severe head injury based on magnetic resonance imaging.
AB  - OBJECT: In 1991 a new pioneering classification of severe head injuries had been
      proposed, based on CT findings. Unfortunately CT cannot visualise all lesions.
      Especially brain stem lesions may escape CT in spite of modern equipment, but may
      be demonstrated by MRI. The high incidence of CT negative but MRI positive
      posttraumatic brain stem lesions has already been demonstrated in a limited
      number of cases. A statistically significant evaluation is still missing.
      Therefore we have investigated a series of 102 comatose patients, in whom a
      statistical evaluation of MRI findings and their correlation with mortality and
      outcome of survivors was possible. PATIENTS AND METHODS: MRI was obtained within
      8 days after servere head injury in 102 patients with a minimum of 24 hours of
      coma. The location of the lesions. identified by a neuroradiologist who was
      unaware of the clinical findings, was correlated with mortality, outcome of
      surviors and duration of coma. The correlation was analysed statistically. Follow
      up ranged from 3 months to 3 years with a mean of 22 months. Four groups of
      lesions gave significant correlations: Grade I lesions were lesions of the
      hemispheres only; Grade II lesions were unilateral lesions of the brain stem at
      any level with or without supratentorial lesions; Grade III lesions were
      bilateral lesions of the mesencephalon with or without supratentorial lesions.
      Grade IV lesions were bilateral lesion of the pons with or without any of the
      foregoing lesions of lesser grades. RESULTS: Mortality increased from 14% in
      grade I lesions to 100% in grade IV lesions. The Glasgow outcome score differed
      significantly for each grade. The mean duration of coma increased from 3 days in
      grade I patients to 13 days in grade III. The correlations between the lesions
      grade I to IV with mortality, outcome of survivors and duration of coma were
      highly significant. CONCLUSION: The statistically significant correlations
      between the 4 groups of severe head injury patients, as identified by MRI, with
      mortality and outcome of survivors justify a new classification based on early
      MRI findings.

PMID- 11460915
TI  - Neurosurgery in Belgium.

PMID- 11460916
TI  - The therapeutic effect of continuous intracisternal L-Arginine infusion on
      experimental cerebral vasospasm.
AB  - BACKGROUND: Recent studies on the pathogenesis of cerebral vasospasm following
      subarachnoid haemorrhage (SAH) suggest a breakdown of the balance between the
      vasoconstrictor and vasodilator systems. A shortage of a major cerebral
      vasodilator, nitric oxide (NO), has been accused of causing this breakdown. We
      investigated the effect of continuous intracisternal infusion of a NO precursor,
      L-Arginine, in a rabbit SAH model. METHOD: Three experimental groups were
      designated: Group 1--Cerebral blood flow (CBF) data was obtained via transorbital
      Doppler ultrasonography (TDU) in 8 normal rabbits. Group 2--Intracisternal
      catheter placement and TDU study during saline infusion were performed in 8
      animals at the 4th day of SAH, Group 3--SAH occurred in 8 animals. 4 days later,
      L-Arginine was infused intracisternally for 1 hour, while TDU was performed
      before and during infusion. CBF parameters which were obtained via TDU
      measurement or calculations, were compared. FINDINGS: The results of TDU revealed
      significant vasospasm in all SAH animals, as well as resolution of vasospasm with
      L-Arginine infusion. After 20 minutes of infusion, a steady and sustained
      vasodilation was obtained in the third group. The analysis of CBF data revealed a
      significant difference in SAH values, and no difference in control animals.
      INTERPRETATION: Our results support the contribution of the "NO shortage" concept
      in the pathogenesis of cerebral vasospasm and overconsumption of L-Arginine
      during the post-SAH period may cause this shortage. L-Arginine treatment may be
      useful for the prophylaxis and treatment of cerebral vasospasm. The
      intracisternal infusion method can eliminate the short action time disadvantage
      of L-Arginine.

PMID- 11460917
TI  - Expression and distribution of beta amyloid precursor protein and beta amyloid
      peptide in reactive astrocytes after transient middle cerebral artery occlusion.
AB  - BACKGROUND: In the brains of Alzheimer's disease patients, beta amyloid protein
      is the major component of senile plaque. In ischemic stress, beta amyloid
      precursor protein (APP) and beta amyloid peptide are reported to be upregulated.
      METHOD: Using Male Wistar-ST rats, expression and distribution of APP and beta
      amyloid peptide were examined immunohistochemically after transient ischemia
      induced by a 2-h middle cerebral artery occlusion (MCAO). After reperfusion for
      3, 7, 14, 30 and 60 days, brains were removed and immunostaining was performed.
      FINDINGS: The reactive astrocytes with APP were observed in the periphery of
      infarct from 3 days to 60 days post-occlusion. The immunoreactivity of beta
      amyloid peptide was also localized in the reactive astrocytes in the peripheral
      zone of infarct at 7, 14, and 30 days post-occlusion. However, beta amyloid
      expression was not identified at 3 days or 60 days post MCAO. Transient ischemia
      temporarily induced beta amyloid peptide expression in reactive astrocytes, but
      this expression peaked at 30 days and disappeared at 60 days. INTERPRETATION:
      These findings suggested that beta amyloid peptide was derived from the
      processing of APP produced in the same reactive astrocytes and the production of
      the peptide stopped within 60 days after the ischemic stress.

PMID- 11460918
TI  - Radiologically confirmed de novo glioblastoma multiforme and hippocampal
      sclerosis associated with the first onset of nonconvulsive simple partial status
      epilepticus.
AB  - The authors report a case of an unusual progression of glioblastoma multiforme in
      the temporal lobe associated with the first onset of nonconvulsive simple partial
      status epilepticus (SPSE), a rare form of status epilepticus. The patient
      underwent a left temporal craniotomy and the tumor was removed. Concurrently, the
      hippocampus was removed as well. The pathological diagnosis of the tumor and the
      hippocampus were glioblastoma multiforme and hippocampal sclerosis. The patient's
      postoperative course was uneventful.

PMID- 11460919
TI  - Laparoscopic anterior lumbar interbody fusion precipitating pituitary apoplexy.
AB  - OBJECTIVE: Pituitary apoplexy may be the first presentation of a previously
      undiagnosed pituitary adenoma. Although many mechanisms of pituitary apoplexy
      have been proposed in the literature, the exact pathogenesis remains unclear.
      Many predisposing events have been implicated in the pathogenesis, however, the
      role of laparoscopy precipitating pituitary apoplexy has not been previously
      described. The authors present a case of pituitary apoplexy in a previously
      undiagnosed pituitary adenoma, which presented in the immediate post-operative
      period after a laparoscopic anterior lumbar interbody fusion. CLINICAL
      PRESENTATION: A 45-year-old man presented with a sudden onset of headache,
      photophobia, diplopia, visual field deficits, and decreased visual acuity in the
      immediate post-operative period after an uneventful laparoscopic anterior lumbar
      interbody fusion. Results of computed tomography of the brain revealed a
      hyperdense suprasellar mass without any signs of subarachnoid blood. The patient
      underwent magnetic resonance imaging, which revealed a hemorrhagic pituitary
      tumor with lateral and suprasellar extension, with compression of the cavernous
      sinus and optic chiasm, respectively. An urgent transsphenoidal decompression of
      the hemorrhagic pituitary adenoma was performed. Post-operatively, the patient
      demonstrated marked neurological improvement with recovery of visual acuity and
      extraocular movements. CONCLUSION: To the authors' knowledge, this is the first
      case reported in the literature of a laparoscopic procedure precipitating
      pituitary apoplexy. Recognition of this rare complication of laparoscopic
      surgery, and the importance of rapid diagnosis and urgent surgical treatment are
      emphasized.

PMID- 11460920
TI  - MRA demonstration of "periarteritis" in Tolosa-Hunt syndrome.
AB  - BACKGROUND: Modern magnetic resonance imaging (MRI) diagnosis of Tolosa-Hunt
      syndrome rests upon demonstration of cavernous sinus abnormalities. We present a
      case of Tolosa-Hunt syndrome who has no abnormal mass lesion in the cavernous
      sinuses on MRI but with a diagnostic lesion on magnetic resonance angiography
      (MRA). CLINICAL PRESENTATION: A 48-year-old woman developed acute periorbital
      pain and abducens palsy of the right side at the first episode, and subacute peri
      orbital pain and rapidly deteriorating visual acuity on the left side at the
      second episode with a four months interval. MRI showed no soft-tissue abnormality
      in the cavernous sinuses. FINDINGS: MRA demonstrated a narrowing of the right
      cavernous carotid artery at the first episode, and narrowings of the left clinoid
      carotid and ophthalmic arteries at the second episode. Based on these findings,
      the patient underwent urgent steroid therapy and the symptoms resolved
      dramatically in each episode. Follow-up MRA confirmed resolution of arterial
      narrowings. INTERPRETATION: MRA may help prompt the noninvasive diagnosis in
      certain cases of Tolosa-Hunt syndrome with little inflammatory reaction in the
      cavernous sinus but with predominant intra- and juxta-cavernous periarteritis.

PMID- 11460921
TI  - Intracranial subfrontal schwannoma.

PMID- 11460922
TI  - A new type-II NADH dehydrogenase from the archaeon Acidianus ambivalens:
      characterization and in vitro reconstitution of the respiratory chain.
AB  - A new type-II NADH dehydrogenase (NDH-II) was isolated from the
      hyperthermoacidophilic archaeon Acidianus ambivalens. This enzyme is a monomer
      with an apparent molecular mass of 47 kDa, containing a covalently bound flavin,
      and no iron-sulfur clusters. Upon isolation, NDH-II loses activity, which can,
      nevertheless, be restored by incubation with phospholipids. Catalytically, it is
      a proficient NADH:caldariella quinone oxidoreductase (130 mmol NADH oxidized/mg
      protein(-1)/min(-1)) but it can also donate electrons to synthetic quinones,
      strongly suggesting its involvement in the respiratory chain. The apparent Km for
      NADH was found to be approximately 6 microM, both for the purified and membrane
      integrated enzyme, thus showing that detergent solubilization and purification
      did not affect the substrate binding site. Further, it is the first example of a
      type-II NADH dehydrogenase that contains the flavin covalently attached, which
      may be related to the need to stabilize the otherwise labile cofactor in a
      thermophilic environment. A fully operative minimal version of Acidianus
      ambivalens respiratory system was successfully reconstituted into artificial
      liposomes, using three basic components isolated from the organism: the type-II
      NADH dehydrogenase, caldariella quinone, the organism-specific quinone, and the
      aa3 type quinol oxidase. This system, which mimics the in vivo chain, is
      efficiently energized by NADH, driving oxygen consumption by means of the
      terminal oxidase.

PMID- 11460923
TI  - First expression and characterization of a recombinant CuA-containing subunit II
      from an archaeal terminal oxidase complex.
AB  - The branched respiratory chain of the archaeon Sulfolobus acidocaldarius contains
      a supercomplex, SoxM, consisting of a bc1-like subcomplex and a terminal oxidase
      moiety, including a subunit II analogous polypeptide, SoxH. However, the latter
      component has never been identified in preparations of SoxM. We demonstrate the
      presence of an mRNA transcript by Northern analysis. We succeeded in cloning and
      expressing the respective gene with truncated N-terminus by deleting a 20 AS
      membrane anchor, which resulted in a water-soluble purple copper protein, which
      was further characterized. The recombinant subunit II of the SoxM complex
      contains a correctly inserted binuclear CuA cluster as revealed by UV/vis and EPR
      spectroscopy. The protein is highly thermostable and displays a redox potential
      of +237 mV. In recombinant form, the metal interacts with cytochrome c as an
      artificial electron donor; the physiological electron donor is still unknown,
      since S. acidocaldarius does not contain any c-type cytochromes. The purple
      copper center of SoxM shows an interesting pH dependency with a pKa at 6.4,
      suggesting protonation of the Cu-ligating histidines. Further lowering the pH
      causes a reversible transition into another cluster form with concomitant
      liberation of one copper. It may thus provide a model for the study of cluster
      rearrangements in response to pH.

PMID- 11460924
TI  - Properties of bound inorganic phosphate on bovine mitochondrial F1F0-ATP
      synthase.
AB  - Beef-heart mitochondrial F1F0-ATP synthase contained six molecules of bound
      inorganic phosphate (Pi). This phosphate exchanged completely with exogenous 32Pi
      when the enzyme was exposed to 30% (v/v) dimethyl sulfoxide (DMSO) and then
      returned to a DMSO-free buffer (Beharry and Bragg 2001). Only two molecules were
      replaced by 32Pi when the enzyme was not pretreated with DMSO. These two
      molecules of 32Pi were not displaced from the enzyme by the treatment with 1 mM
      ATP. Similarly, two molecules of bound 32Pi remained on the DMSO-pretreated
      enzyme following addition of ATP, that is, four molecules of 32Pi were displaced
      by ATP. The ATP-resistant 32Pi was removed from the enzyme by pyrophosphate. It
      is proposed that these molecules of 32Pi are bound at an unfilled adenine
      nucleotide-binding noncatalytic site on the enzyme. Brief exposure of the enzyme
      loaded with two molecules of 32Pi to DMSO, followed by removal of the DMSO,
      resulted in the loss of the bound 32Pi and in the formation of two molecules of
      bound ATP from exogenous ADP. A third catalytic site on the enzyme was occupied
      by ATP, which could undergo a Pi <--> ATP exchange reaction with bound Pi. The
      presence of two catalytic sites containing bound Pi is consistent with the X-ray
      crystallographic structure of F1 (Bianchet, et al., 1998). Thus, five of the six
      molecules of bound Pi were accounted for. Three molecules of bound Pi were at
      catalytic sites and participated in ATP synthesis or Pi <--> ATP exchange. Two
      other molecules of bound Pi were present at a noncatalytic adenine nucleotide
      binding site. The location and role of the remaining molecule of bound Pi remains
      to be established. We were unable to demonstrate, using chemical modification of
      sulfhydryl groups by iodoacetic acid, any gross difference in the conformation of
      F1F0 in DMSO-containing compared with DMSO-free buffers.

PMID- 11460925
TI  - Ca2+ induces a cyclosporin A-insensitive permeability transition pore in isolated
      potato tuber mitochondria mediated by reactive oxygen species.
AB  - Oxidative damage of mammalian mitochondria induced by Ca2+ and prooxidants is
      mediated by the attack of mitochondria-generated reactive oxygen species on
      membrane protein thiols promoting oxidation and cross-linkage that leads to the
      opening of the mitochondrial permeability transition pore (Castilho et al.,
      1995). In this study, we present evidence that deenergized potato tuber (Solanum
      tuberosum) mitochondria, which do not possess a Ca2+ uniport, undergo inner
      membrane permeabilization when treated with Ca2+ (>0.2 mM), as indicated by
      mitochondrial swelling. Similar to rat liver mitochondria, this permeabilization
      is enhanced by diamide, a thiol oxidant that creates a condition of oxidative
      stress by oxidizing pyridine nucleotides. This is inhibited by the antioxidants
      catalase and dithiothreitol. Potato mitochondrial membrane permeabilization is
      not inhibited by ADP, cyclosporin A, and ruthenium red, and is partially
      inhibited by Mg2+ and acidic pH, well known inhibitors of the mammalian
      mitochondrial permeability transition. The lack of inhibition of potato
      mitochondrial permeabilization by cyclosporin A is in contrast to the inhibition
      of the peptidylprolyl cis-trans isomerase activity, that is related to the
      cyclosporin A-binding protein cyclophilin. Interestingly, the monofunctional
      thiol reagent mersalyl induces an extensive cyclosporin A-insensitive potato
      mitochondrial swelling, even in the presence of lower Ca2+ concentrations (>0.01
      mM). In conclusion, we have identified a cyclosporin A-insensitive permeability
      transition pore in isolated potato mitochondria that is induced by reactive
      oxygen species.

PMID- 11460926
TI  - Mitochondrial adaptation to in vivo polyunsaturated fatty acid deficiency:
      increase in phosphorylation efficiency.
AB  - Polyunsaturated fatty acid (PUFA) deficiency affects respiratory rate both in
      isolated mitochondria and in hepatocytes, an effect that is normally ascribed to
      major changes in membrane composition causing, in turn, protonophoriclike
      effects. In this study, we have compared the properties of hepatocytes isolated
      from PUFA-deficient rats with those from control animals treated with
      concentrations of the protonophoric uncoupler 2,4-dinitrophenol (DNP). Despite
      identical respiratory rate and in situ mitochondrial membrane potential (delta
      psi), mitochondrial and cytosolic ATP/ADP-Pi ratios were significantly higher in
      PUFA-deficient cells than in control cells treated with DNP. We show that PUFA
      deficient cells display an increase of phosphorylation efficiency, a higher
      mitochondrial ATP/ADP-Pi ratio being maintained despite the lower delta psi. This
      is achieved by (1) decreasing mitochondrial Pi accumulation, (2) increasing ATP
      synthase activity, and (3) by increasing the flux control coefficient of adenine
      nucleotide translocation. As a consequence, oxidative phosphorylation efficiency
      was only slightly affected in PUFA-deficient animals as compared to protonophoric
      uncoupling (DNP). Thus, the energy waste induced by PUFA deficiency on the
      processes that generate the proton motive force (pmf) is compensated in vivo by
      powerful adaptive mechanisms that act on the processes that use the pmf to
      synthesize ATP.

PMID- 11460927
TI  - A novel K+ channel expressed in carrot roots with a low susceptibility toward
      metal ions.
AB  - Kdc1 is a novel K+-channel gene cloned from carrot roots, and which is also
      present in cultured carrot cells. We investigated the characteristics of the
      ionic current elicited in Xenopus oocytes coinjected with KDC1 (K+-Daucus carota
      1) and KAT1 (from Arabidopsis thaliana) RNA. Expressed heteromeric channels
      displayed inward-rectifying potassium currents whose kinetics, voltage
      characteristics, and inhibition by metal ions depended on KDC1:KAT1 ratios. At
      low KDC1:KAT1 ratios, Zn2+ inhibition of heteromeric K+ current was less
      pronounced compared to homomeric KAT1 channels, while at higher KDC1:KAT1 ratios,
      the addition of Zn2+ even produced an increase in current. Under the same
      conditions, the Ni2+ inhibition of the current was also reduced, but no current
      increase was observed. These effects might be explained by the unusual amino acid
      composition of the KDC1 protein in terms of histidine residues that are absent in
      the pore region, but abundant (four per subunit) in the proximity of the pore
      entrance. Channels like KDC1 could be at least partially responsible for the
      higher resistance of carrot cells in the presence of metals.

PMID- 11460928
TI  - Carcinogen-induced, free radical-mediated reduction in microsomal membrane
      fluidity: reversal by indole-3-propionic acid.
AB  - Chromium (Cr) is a well established carcinogen, with Cr(III) accounting for much
      of the intracellular oxidative damage that this transition metal induces. Indole
      3-propionic acid (IPA), a melatonin-related molecule, is a reported antioxidant
      and free radical scavenger. Concentration (1, 10, 100, 500, or 1000 microM) and
      time (15, 30, 45, 60, or 90 min)-dependent effects of Cr(III) in the presence of
      H2O2 (0.5 mM), as well as the protective effect of IPA on Cr(III)-induced
      alterations in membrane fluidity (the inverse of membrane rigidity), as an index
      of membrane damage, were estimated by fluorescence spectroscopy. Cr(III), in a
      concentration- and a time-dependent manner, decreased membrane fluidity, with
      marked effects at a concentration of 500 microM and 60 min of incubation. IPA (5,
      3, or 1 mM) prevented the Cr(III)-induced decrease in membrane fluidity. It is
      concluded that the carcinogen Cr(III), in the presence of H202, generates free
      radicals, which decrease membrane fluidity in rat microsomal membranes. Membrane
      alterations are pharmacologically prevented by the antioxidant IPA.

PMID- 11460929
TI  - A comprehensive phylogenetic analysis of Rieske and Rieske-type iron-sulfur
      proteins.
AB  - The Rieske iron-sulfur center consists of a [2Fe-2S] cluster liganded to a
      protein via two histidine and two cysteine residues present in conserved
      sequences called Rieske motifs. Two protein families possessing Rieske centers
      have been defined. The Rieske proteins occur as subunits in the cytochrome bc1
      and cytochrome b6f complexes of prokaryotes and eukaryotes or form components of
      archaeal electron transport systems. The Rieske-type proteins encompass a group
      of bacterial oxygenases and ferredoxins. Recent studies have uncovered several
      new proteins containing Rieske centers, including archaeal Rieske proteins,
      bacterial oxygenases, bacterial ferredoxins, and, intriguingly, eukaryotic Rieske
      oxygenases. Since all these proteins contain a Rieske motif, they probably form a
      superfamily with one common ancestor. Phylogenetic analyses have, however, been
      generally limited to similar sequences, providing little information about
      relationships within the whole group of these proteins. The aim of this work is,
      therefore, to construct a dendrogram including representatives from all Rieske
      and Rieske-type protein classes in order to gain insight into their evolutionary
      relationships and to further define the phylogenetic niches occupied by the
      recently discovered proteins mentioned above.

PMID- 11460930
TI  - Detection of restenosis after percutaneous transluminal coronary angioplasty
      using the exercise treadmill test and technetium 99m-sestamibi scintigraphy.
AB  - BACKGROUND: The detection of myocardial ischemia after percutaneous transluminal
      coronary angioplasty (PTCA) is important because 30-50 per cent of the patients
      will develop restenosis within 6 months. Symptoms of chest pain and exercise
      stress test (EST) have shown to be less sensitive for detection of ischemia than
      exercise Technetium-99m Sestamibi (Tc-99m MIBI). The purpose of this study was to
      compare the sensitivity and specificity of chest pain, EST and Tc-99m MIBI with
      coronary angiography (CAG). METHOD: Tc-99m MIBI with SPECT imaging was performed
      at months 1, 3 and 6 and CAG was repeated 6 months after successful PTCA. Earlier
      Tc-99m MIBI and CAG were performed in patients with recurrent angina pectoris or
      suspected restenosis. RESULTS: Forty six patients (M 29, F 17) who had undergone
      successful angioplasty were prospectively enrolled. Their mean age was 61 +/- 19
      yrs. Eighty eight lesions (LAD63%, LCX34%, RCA19%) were performed. Lesion
      characteristics were type A in 9 per cent, type in B 30 per cent and type C in 61
      per cent. Fifty four per cent of PTCA were performed for single vessel disease
      and 46 per cent for multivessel disease. The mean duration of time between PTCA
      and follow-up CAG was 6.1 +/- 2.7 months. We detected restenosis from CAG in 58
      per cent of the cases. The Tc-99m MIBI had higher sensitivity to detect
      restenosis than anginal pain (85.0% vs 39.4% p < 0.005) or EST (85.0% vs 63.6% p
      < 0.05) when compared with CAG. The overall accuracy of Tc-99m MIBI for the
      detection of restenosis was 80 per cent. CONCLUSION: Tc-99m MIBI with SPECT
      imaging constitutes a better means than symptoms or exercise test to detect
      restenosis after successful coronary angioplasty.

PMID- 11460931
TI  - Exchange transfusion in severe falciparum malaria: a simple method modified from
      hemodialysis circuit.
AB  - We set up a simple extracorporeal circuit, modified from the extracorporeal
      method generally used in conventional hemodialysis, for exchange transfusion.
      Temporary vascular access was used in exchange transfusion for both draining the
      infected blood and infusion of the freshly non-infected blood. This method of
      exchange transfusion was performed in 3 severe complicated falciparum malaria
      patients who had a percentage of parasitemia of 80, 40, and 35. The magnitude of
      parasitemia decreased immediately to less than one per cent and this value
      persisted twenty-four hours after the procedure. No complications of exchange
      transfusion were detected in all patients. Erythrocyte morphology determined by
      scanning electron microscopy was unaltered by exchange transfusion. Because of
      the simplicity, the effectiveness, and the safety of the procedure, this
      extracorporeal circuit modified from hemodialysis circuit would be a more
      beneficial exchange transfusion method in the treatment of severe complicated
      falciparum malaria than the manually-performed one.

PMID- 11460932
TI  - Necrotizing enterocolitis: a comparison between full-term and pre-term neonates.
AB  - A retrospective study comparing 16 full-term and 18 pre-term neonates with NEC
      operated on at Siriraj Hospital between 1987 and 1999 is presented. Major risk
      factors leading to NEC in full-term neonates included sepsis, SGA, birth
      asphyxia, severe jaundice requiring exchange transfusion and chorioamnionitis.
      Although full-term neonates developed NEC earlier than pre-term neonates (8.56
      days vs 12.78 days), the average ages of operation in both groups were the same.
      There was no difference in CBC and bacteriological culture's results between term
      and pre-term patients. The decision to conduct operative treatments for full-term
      neonates with NEC was mostly based on only clinical signs of peritonitis (56.25%)
      before the pneumoperitoneum developed (31.25%). Ileo-caecal region was the most
      common site of bowel necrosis in both premature and full-term infants. Although
      term infants had a better 3-month survival rate than pre-term neonates (75% and
      61% respectively), both groups had the same surgical complication rates.

PMID- 11460933
TI  - A simple prediction rule and a neural network model to predict pancreatic beta
      cell reserve in young adults with diabetes mellitus.
AB  - In the present study we developed and assessed the performance of a simple
      prediction rule and a neural network model to predict beta-cell reserve in young
      adults with diabetes. Eighty three young adults with diabetes were included in
      the study. All were less than 40 years old and without apparent secondary causes
      of diabetes. The subjects were randomly allocated to 2 groups; group 1 (n = 59)
      for developing a prediction rule and training a neural network, group 2 (n = 24)
      for validation purpose. The prediction rule was developed by using stepwise
      logistic regression. Using stepwise logistic regression and modification of the
      derived equation, the patient would be insulin deficient if 3(waist circumference
      in cm) + 4(age at diagnosis) < 340 in the absence of previous diabetic
      ketoacidosis (DKA) or < 400 in the presence of previous DKA. When tested in the
      validation set, the prediction rule had positive and negative predictive values
      of 86.7 per cent and 77.8 per cent respectively with 83.3 per cent accuracy while
      the ANN model had a positive predictive value of 88.2 per cent and a negative
      predictive value of 100 per cent with 91.7 per cent accuracy. When testing the
      performance of the prediction rule and the ANN model compared to the assessment
      of 23 internists in a subgroup of 9 diabetics whose age at onset was less than 30
      years and without a history of DKA, the ANN had the highest ability to predict
      beta-cell reserve (accuracy = 88.9), followed by the prediction rule (accuracy =
      77.8%) and assessments by internists (accuracy = 60.9%). We concluded that beta
      cell reserve in young adults with diabetes mellitus could be predicted by a
      simple prediction rule or a neural network model. The prediction rule and the
      neural network model can be helpful clinically in patients with mixed clinical
      features of type 1 and type 2 diabetes.

PMID- 11460934
TI  - CO2 laser surgery in otorhinolaryngology-site and complications: a 10-year
      experience at Ramathibodi Hospital.
AB  - OBJECTIVE: To present data on ten years' experience in CO2 laser surgery and
      associated complications among otorhinolayngologic patients. MATERIAL AND METHOD:
      The study involved examining records of otorhinolaryngologic patients who
      underwent CO2 laser operations during a 10-year period (July 1, 1986-June 30,
      1996). The sample consisted of 733 patients: 370 male and 363 female patients.
      CO2 laser surgery in otorhinolaryngology was first used in Ramathibodi Hospital
      on July 10, 1986. RESULTS: These patients were aged 2 months to 93 years with the
      mean age of 24.3 years (median = 16 years). Among 1,725 operations, 1,570
      operations (91%) were performed under general anesthesia and 155 operations (9%)
      were performed under local anesthesia. In our series, the most frequent sites for
      laser surgery were as follows: larynx (77.22%), oral cavity and oropharynx
      (12.64%), skin (5.04%) and nose and paranasal sinuses (3.31%). Intraoperative
      complications occurred in 18 out of 1,725 (intra-operative complication rate of
      1%). Laser-related complications were found in 13 out of 1,725 operations (0.75%)
      and non laser-related complications were found in 5 out of 1,725 operations
      (0.25%). There was no mortality. CONCLUSION: CO2 laser is a useful modality of
      treatment in otorhinolaryngologic surgery especially in the larynx. Our
      experience demonstrates the relative low incidence of complications (1%) and no
      mortality in otorhinolaryngology head and neck surgery.

PMID- 11460935
TI  - Dependence and active life expectancy of the elderly population living in the
      central region of Thailand.
AB  - OBJECTIVE: To determine the prevalence and the independent socio-economic factors
      with respect to the dependence status of the Thai elderly population living in
      the central region and to calculate the active life expectancy (ALE) based on the
      results of this survey and abridged life tables for Thailand. DESIGN: A cross
      sectional mulitistage random sampling survey. SETTING: Communities in the central
      region, Thailand. SUBJECTS: 723 elderly subjects. RESULTS: Mean age and its
      standard deviation (SD) of the 723 recruited subjects were 69.9 and 7.3 years,
      respectively. Forty three per cent of the subjects were men. Mean values (SD) of
      the BAI score and the CAI score were 18.78 (2.6) and 6.47 (2.4), respectively.
      Except for housework, elderly women had a higher prevalence rate of dependence on
      activities of daily living (ADL) compared with elderly men. Seven univariate
      factors of the BAI and the CAI were demonstrated. According to the multiple
      linear regression analysis by entering all univariate factors of the BAI and the
      CAI except "working status", independent factors of both the BAI (adjusted R2 =
      0.051) and the CAI (adjusted R2 = 0.146) were age, sex and writing ability. The
      prevalence rate (95% confidence interval) of dependence regarding self-care
      activities of daily living was 5.9 per cent (4.2-7.6%). The rate of dependence
      increased with age. The female elderly were more dependent on self care than
      their male counterparts. Although the elderly women live longer than the elderly
      men, they spend more years in a severely dependent state. Findings on ratios
      between health and life expectancy demonstrate that Thai men spend more
      proportional time leading a healthy life than Thai women. CONCLUSION: Prevalence
      rates of dependence regarding activities of daily living among the Thai elderly
      living in the Central region were rather high showing the health of elderly women
      to be worse than that of elderly men. The elderly women spend more years in a
      severely dependent state although they live longer than the elderly men.

PMID- 11460936
TI  - Comparison of the OptiMAL rapid test with routine microscopic examination of
      Giemsa-Stained Thick Blood Film for diagnosis of malaria.
AB  - The OptiMAL is a rapid immunodiagnostic test developed by Flow Inc., Portland,
      Oreg. for diagnosis and differentiation of P. falciparum and non P. falciparum
      malaria infection. It has been based on detection of circulating parasite lactate
      dehydrogenase enzyme (pLDH), produced by live Plasmodium parasites. The purpose
      of this study was to compare the efficacy of the OptiMAL test with routine
      microscopic examination of Giemsa-Stained Thick Blood Film (routine GS-TBF) for
      the diagnosis of malaria at a local malaria clinic in a hyperendemic area of
      Thailand by using a standard GS-TBF (standard GS-TBF) as reference. One hundred
      and seventy five patients attending the clinic were recruited; 50, 42 and 83 were
      falciparum malaria, vivax malaria and non-malaria patients, respectively.
      Compared with the reference, the OptiMAL test had sensitivities of 92 per cent
      and 97.6 per cent, whereas, the routine GS-TBF had sensitivities of 81.3 per cent
      and 81 per cent for the detection of P. falciparum and P. vivax, respectively.
      Both tests showed no false positive resulting in 100 per cent specificities.
      However, the OptiMAL test was able to detect only 20 per cent of infection with
      less than 200 parasitaemia/microlitre. It was also shown in our study that the
      OptiMAL test was advantageous in follow-up of the treatment outcome. No false
      positive occurred among 40 follow-up cases. The OptiMAL test detected malaria
      infection more accurately than the routine GS-TBF (p < 0.05) and was simple, easy
      to perform and rapid. It is an alternative tool for the diagnosis of malaria in a
      hyperendemic area where experienced microscopists are not available.

PMID- 11460937
TI  - Transvaginal sonography for fetal crown-rump length measurement in a Thai
      population.
AB  - A prospective descriptive cross-sectional study was undertaken at the Department
      of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University to
      establish a reference interval for fetal crown-rump length (CRL) in a Thai
      population using transvaginal ultrasound. This study was performed on normal
      pregnant women registered at the antenatal clinic in their first trimester. All
      had a good menstrual history. CRL measurement was obtained by a 5 MHz vaginal
      probe. All of the newborns were proved to be normal at birth. We constructed and
      compared CRL (mm) relating to gestational age (GA) (days). Five hundred and forty
      seven cases were enrolled into the study. CRL was correlated with gestational
      age. The best fit regression equation was the quadratic model: CRL (mm) = -13.872
      - 0.014 GA (day) + 0.0097 GA (day)2, R = 0.92, p < 0.0001). Centiles and a chart
      for CRL derived from the regression equation are presented. In conclusion, a
      reference interval for fetal crown-rump length in a Thai population has been
      established. This data may be useful in the early detection of genetic or
      environmental disorders affecting fetal growth in the first trimester of
      pregnancy.

PMID- 11460938
TI  - Distribution of minor salivary glands in the peritonsillar space.
AB  - Minor salivary glands can usually be found along the mucous membrane of the upper
      aerodigestive tract. Their presence in the peritonsillar space was of little
      interest until it was postulated that infection of Weber's gland (minor salivary
      gland at the superior pole of the peritonsillar space) might be the possible
      cause of peritonsillar abscess. This study was designed to examine the
      distribution of minor salivary glands in the peritonsillar space and their role
      in pathogenesis of peritonsillar abscess. Tonsillectomy specimens from fifty-five
      patients who were suffering from repeated tonsillitis, obstructive sleep apnea,
      tonsillar mass and peritonsillar abscess at Srinagarind Hospital from September
      1995 to November 1996 were histologically examined. The locations of these minor
      salivary glands were found at the upper, middle, and lower portions of the
      peritonsillar space. This small sample study precludes any definitive statement
      regarding the association of Weber's gland and the pathogenesis of peritonsillar
      abscess.

PMID- 11460939
TI  - The usefulness of X-linked polymorphic loci as gene markers to track X allele and
      chimerism in a post-allogeneic peripheral blood stem cell transplant patient with
      Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized
      by progressive T-cell immunodeficiency. Laboratory findings generally demonstrate
      reduced response to T-cell mitogens, markedly decreased serum concentration of
      IgM, and thrombocytopenia with small platelet volume. Allogeneic HLA-matched
      sibling bone marrow transplantation (BMT) can correct this disorder. We report
      the usefulness of X-linked polymorphic loci to detect X-allele gene tracking
      among WAS siblings and chimerism between a pre- and post-allogeneic matched
      sibling peripheral blood stem cell transplantation (PBSCT). A 3 1/2 year old boy
      with clinical and laboratory findings consistent with WAS underwent allogeneic
      matched sibling PBSCT. We used BclI restriction fragment length polymorphism
      (RFLP) of intron 18 of factor VII gene and MseI RFLP of the 5' flanking region of
      factor IX gene to detect X-allele gene tracking among siblings and family members
      and chimerism in patients between pre-and post-allogeneic matched sibling PBSCT.
      We were able to demonstrate that determination of BclI and MseI RFLP can be
      employed to recognize the difference in X-allele genes between the recipient and
      donor for allogeneic matched sibling PBSCT. The authors also were able to
      demonstrate that these polymorphic loci can detect full chimerism of donor
      hematopoietic cells in recipient blood after allogeneic PBSCT. This finding was
      correlated with improvement of post-PBSCT clinical and laboratory findings. BclI
      and MseI RFLP associated with X-chromosome can effectively track X-allele, detect
      carrier state, and demonstrate the different X-allele among male siblings, and
      chimerism of hematopoietic cells between donors and recipients in a setting of
      allogeneic matched sibling BMT or PBSCT for X-linked hereditary diseases such as
      Wiskott-Aldrich syndrome.

PMID- 11460940
TI  - Puffer fish poisoning: clinical features and management experience in 25 cases.
AB  - Between 1989 and 1999, 25 cases of puffer fish poisoning (PFP) were admitted to
      the medical service of Chon Buri Hospital. The severity of the poisoning was
      classified into four stages based on clinical signs and symptoms of PFP. Of the
      25 patients, 23 were males and 2 were females. Three patients were in stage 1,
      four were in stage 2 and eighteen were in stage 4. Paresthesia was the early
      presenting complaint of all patients. Paresthesia consisting of either numbness
      or tingling of lips, tongue, around the mouth, hands, and feet. Muscle weakness,
      dizziness, vertigo, nausea and vomiting were common complaints. Eighteen patients
      developed acute flaccid paralysis and respiratory failure requiring ventilatory
      support. All patients received symptomatic and supportive treatment and general
      supportive care, including gastric lavage and intravenous fluid. Intubation and
      mechanical ventilation was considered especially when paralysis was progressing
      rapidly. Most were taken off the respirator 12-48 hours later. All patients
      completely recovered without any sequelae. Clinical features of PFP, toxicity of
      puffer fish and management were discussed.

PMID- 11460941
TI  - Prediction of bone mineral density of lumbar spine, hip, femoral neck and Ward's
      triangle by forearm bone mineral density.
AB  - Bone mineral density (BMD) of dual energy X-ray absorptiometry (DEXA) at both
      radius and ulna were measured to evaluate the correlation of those and BMD at
      lumbar (L) spine, hip, femoral neck and Ward's triangle. The 64 simple linear
      regression analysis was calculated to postulate the predicted equation by using
      the BMD at supradistal, distal 1/10, distal 1/6 and distal 1/3 of both forearms
      as independent variables, while the dependent variables were BMD at L1-L4 spine,
      total hip, femoral neck and Ward's triangle. 115 patients aged between 41-79
      years (mean age 55.97+/-8.34 years) from the menopausal clinic, Pramongkutklao
      Hospital, were scanned at both forearms by Panasonic (DXA-70) DEXA and at non
      forearm regions by Hologic (QDR 4500) DEXA on the same day. The results showed
      that the BMD of each of the 4 parts of both radius and ulna had positive
      correlation to those of L-spine, total hip, femoral neck and Ward's triangle with
      r = 0.4012 to 0.7032 (P<0.001 for all). The greater distal of the forearm, the
      better correlation of BMD to the non forearm BMD. The 64 simple linear regression
      equations were constructed with regression coefficient ranging from 0.6048 to
      1.9011 (P<0.001 for all). When considering the non forearm BMD, the mean BMD at
      Ward's triangle significantly declined more rapidly than that of L-spine, total
      hip and femoral neck (P<0.05 for all). It indicated that there was an early
      change of BMD at Ward's triangle. However, this change followed the forearm BMD.
      Distal forearm BMD was the earliest sign of bone loss. We can predict non forearm
      BMD by supradistal and distal 1/10 of forearm BMD.

PMID- 11460942
TI  - Combination of gemcitabine and cisplatin in advanced non-small cell lung cancer.
AB  - A prospectively designed phase II study of non-small cell lung cancer stage IIIb
      and IV treated by gemcitabine and cisplatin was studied. The dosage of
      gemcitabine was 1 g/m2 weekly on day 1, 8 and 15. Cisplatin 100 mg/m2 was given
      on day 15 of each 28 day cycle. Twenty-eight patients were treated and all cases
      were evaluated for response. Survival and toxicity were determined in all
      enrolled patients. Thirteen (46.4%) achieved partial response (PR). By using
      Kaplan Meier's method the mean survival time was 19.8 months. One year survival
      was 66.6 per cent. Non hematologic toxicity consisted of mild nausea, vomiting,
      alopecia and hyperpigmentation of the skin. Rising creatinine of grade I was seen
      in 1.6 per cent. Anemia and leukopenia were common hematologic side effects with
      27.5 per cent and 14.2 per cent of patients experiencing grade III and IV
      toxicity respectively. Both side effects were usually short lived and responsible
      for the delay of gemcitabine administration on day 8 and 15 in 18.3 per cent and
      23.3 per cent on day 15 alone of chemotherapeutic courses respectively. We
      conclude that the combination of gemcitabine and cisplatin at this dosage
      achieved good response with moderate side effects.

PMID- 11460943
TI  - Medical cost and illness pattern among Ramathibodi medical students.
AB  - BACKGROUND: In Thailand, health care expenditure has increased more than three
      times from the 1982 to 1992. Health care of medical students does not reflect the
      actual costs because of the strong personal relationship between doctors and
      patients (ie. medical students). Many items are waived in the patient's favour.
      The objectives of study in medical students were analysed in unit cost, cost
      recovery, illness pattern and health service uses. METHOD: From May 1997 to April
      1998 the prescription cost and illness pattern were retrospectively studied and
      analysed. There were 1,063 out-patient visits and 8 in-patient cases from 416
      medical student case records of Ramathibodi Hospital. The annual subscription for
      medical student is 700 baht per person per year, but the actual medical costs are
      higher 53,213 baht, excluding investment, materials and labour cost. The most
      common illness was upper respiratory tract infection. The average cost per
      prescription was 163 baht (range 6-1391 baht) and the sixth year students spent
      more than the fourth and fifth years. Frequency of consultation was more in the
      fourth than the fifth and sixth year students and total medical students (namely
      4.01, 1.66, 1.92, 2.55 times/student/year respectively). The consultation was
      done in the emergency room (72.0%) more often than in the health clinic (1.9%).
      CONCLUSION: Medical students should attend special clinics regularly, except in
      an emergency, to get continual medicare and save medical costs. Determining the
      maximum medical cost per student per year is a strategy of saving cost. To
      promote understanding and allay anxiety, medical students should have the benefit
      of health promotion, prevention and orientation as they are in continual contact
      with all forms of contagious diseases. If this preventive measure is effective,
      the incidence of illness should be lower and the cost reduced.

PMID- 11460944
TI  - Cognitive status in the community dwelling Thai elderly.
AB  - OBJECTIVE: To survey the prevalence of cognitive impairment in the elderly and to
      estimate the prevalence of dementia in the community dwelling Thai population. To
      assess the psychometric property of Thai Mental State Examination (TMSE).
      MATERIAL AND METHOD: We conducted a countrywide survey of 3,177 Thai elderly who
      were 60 years old and over from 1995 to 1997. Medical history and ability to
      carry out daily activities were taken by trained medical personnel. Thai Mental
      State Examination (TMSE) was used for cognitive study. Every elderly person
      involved in this study was examined by either an internist or a neurologist.
      Blood was taken for haematological and biochemical analysis. SPSS 6.0 was the
      main statistical analysis of the data. RESULTS: Three thousand one hundred and
      seventy seven elderly people were enrolled in this study, thirty eight point
      eight per cent were male and sixty one point two per cent were female. There was
      correlation between age, education and TMSE (r=-0.345, r=0.473, p<0.001). We
      found no correlation between TMSE, mean arterial blood pressure (BP), systolic
      BP, diastolic BP, haematocrit, cholesterol, triglyceride, blood sugar and
      syphilitic serology. Multiple cut off points of TMSE was proposed to utilise the
      twenty fifth percentile in each five yearly age interval. Those who were under
      the 25th percentile of TMSE and had impaired daily activities were diagnosed as
      dementia. The prevalence of dementia was 9.88 percentiles in our study.
      CONCLUSION: Dementia is a common problem in the Thai elderly. As treatment has
      become available for several etiologies of dementia, early detection and
      assessment of dementia with a cognitive screening test are essential. Public
      education to distinguish between dementia and old age needs to be emphasised.

PMID- 11460945
TI  - Glioma of the central nervous system: factors affecting the outcome.
AB  - Glioma is one of the most common brain tumors but the outcome of treatment is
      still uncertain. The author conducted this study to find the prognostic factors
      affecting the outcome. The medical records of 41 patients, diagnosed as having
      glioma, admitted to the Neurosurgery Division, Prasat Neurological Hospital,
      between January 1998 and December 1999 were retrospectively reviewed. Gender,
      age, history of smoking and alcohol drinking, symptoms and signs, CT and MRI
      findings, underlying pathology, locations of lesions, treatments and outcomes
      were analysed. There were 20 males and 21 females with ages ranging from 2 to 75
      years. The mean age was 39.78 +/- 19.81 years old. The three most common
      presenting symptoms were headache, motor weakness, and seizures. The predominant
      location of the tumors was in the cerebral hemisphere. Most low grade astrocytoma
      show low/iso-density with slight contrast enhanced in CT scan. The patients were
      divided into two groups according to the outcome, improved and dead. Gender, age,
      history of smoking and alcohol drinking, location of tumors did not have any
      effect on the outcome. The factors affecting the outcome of treatment were
      histological subtypes and types of treatment. There was a statistically
      significantly better outcome in low grade astrocytoma and tumor removal with
      irradiation. The overall mortality was 21.95 per cent after two years.

PMID- 11460946
TI  - Comparative study between Westergren and erythrocyte sedimentation pipette method
      for determination of erythrocyte sedimentation rate.
AB  - A comparative study between standard Westergren and erythrocyte sedimentation
      pipette (Sediplast) methods for determination of erythrocyte sedimentation rate
      was performed on 80 individual subjects. From the study, the comparison-of
      methods plot Sediplast method (X) vs Westergren method (Y) gave the least square
      linear regression equation of Y = 1.001 X - 2.24 (r = 0.99). Precision analysis
      gave a coefficient of variation below 3 per cent. The new erythrocyte
      sedimentation pipette method seems to be an effective and safe method for
      erythrocyte sedimentation rate determination in the present day.

PMID- 11460947
TI  - Penicilliosis-associated hemophagocytic syndrome in a human immunodeficiency
      virus-infected child: the first case report in children.
AB  - Infection-associated hemophagocytic syndrome (IAHS) has been found in many
      systemic infectious conditions with a high mortality rate. Disseminated
      Penicillium marneffei infection is a common opportunistic condition among HIV
      infected patients in many regions in Southeast Asia. We report the first case of
      IAHS caused by penicilliosis in an HIV-infected child who presented with
      cytopenias and recovered promptly after antifungal and intravenous immunoglobulin
      therapy.

PMID- 11460948
TI  - Chlamydophila (Chlamydia) pneumoniae as a cause of community-acquired pneumonia
      in Thailand.
AB  - Chlamydophila (Chlamydia) pneumoniae infection is increasingly reported worldwide
      nowadays. We studied twelve Thai adults presenting with the clinical symptoms and
      signs of community-acquired pneumonia (CAP) due to C. pneumoniae (TWAR) at
      Pramongkutklao Hospital in Bangkok, Thailand. Their mean age was 38 (range 21-73)
      years. Six patients lived in Bangkok. Seven patients had comorbid diseases (four
      cases with allergic asthma, one each with diabetes mellitus, chronic obstructive
      pulmonary disease and coronary artery disease). C. pneumoniae pneumonia presented
      as subacute pneumonia in 6 patients. The clinical manifestations were mild (IDSA
      risk class I-III) except in 4 patients who had preexisting allergic asthma, COPD
      and coronary heart disease. The diagnosis of C. pneumoniae pneumonia was based on
      microimmunofluorescence (MIF) antibody technique (IgM titer > or = 1:16, IgG > or
      = 1:512, IgA > or = 1:256 with or without fourfold rises). The clinical
      conditions were consistent with the primary infection (IgM titer of 1:16 or
      higher) in 6 patients and reinfection (IgG titer of 1:512, IgA titer of 1:256 or
      higher without rises of IgM titer) in the other 6 patients. Minimal bilateral
      pleural effusion was detected in only one patient. Coinfection was demonstrated
      in 2 patients (one each with S. pneumoniae and K. pneumoniae). All patients
      markedly improved after a 2-week course of macrolide, doxycycline or newest
      fluoroquinolone therapy. All patients had done well at one year of follow-up. C.
      pneumoniae infection has been recently recognized and a high seroprevalence (37%)
      in Thai school children and 100 per cent in young male Thai military conscripts
      has been reported. This report suggests that this infection, C. pneumoniae, may
      be a common pathogen of CAP in Thailand.

PMID- 11460949
TI  - Hemobilia: four case reports and review of the literature.
AB  - In this report, we present four cases of hemobilia. Hemobilia occurs when
      conditions produce an abnormal communication between blood vessels and bile
      ducts. Although iatrogenic procedures as causes of hemobilia have been reported
      with increasing frequency, non-iatrogenic etiologies are still quite rare. We,
      therefore, report 4 cases of hemobilia secondary to different etiologies found in
      our institution from 1996 to 1998, that are non-iatrogenic. The first patient was
      a case of congenital aneurysm, the second pseudoaneurysm from trauma, the third
      cholangiocarcinoma and the fourth hepatocellular carcinoma. The classical triad
      consists of melena, jaundice and abdominal pain. Direct observation of blood
      flowing from the Ampulla of Vater by endoscopy was the initial diagnostic
      procedure in all four cases. Diagnosis was confirmed by ultrasonography,
      computerized tomography, angiography or surgery. Transcatheter selective
      embolization as a noninvasive treatment for hepatic aneurysm/pseudoaneurysm is
      emphasized.

PMID- 11460950
TI  - Mitochondrial myopathy with respiratory dysfunction: a case report.
AB  - A 50-year-old woman who presented with infective bronchiectasis and respiratory
      insufficiency was reported. Mitochondrial myopathy was diagnosed from a long
      history of chronic bilateral ptosis and external ophthalmoplegia with muscle
      wasting. Muscle biopsy revealed ragged-red fibers. After treatment with
      appropriate antibiotic and respiratory assistance, the patient improved and
      returned to her usual state of health.

PMID- 11460951
TI  - Familial duodenal atresia: a report of two siblings.
AB  - The familial occurrence of duodenal atresia is extremely uncommon. The author
      reports duodenal atresia occurring in two siblings who underwent successful
      surgical repair at the Pediatric Surgical Unit, Department of Surgery, Ratchaburi
      Hospital. To the author's knowledge, this is the first report of familial
      duodenal atresia in Thailand.

PMID- 11460952
TI  - Toxic shock syndrome after anterior-posterior nasal packing.
AB  - Toxic shock syndrome (TSS) is a severe, potentially life-threatening multisystem
      disease. It is rather rare with the incidence estimated to be 16.5/100,000 of
      nasal surgery performed in the United States. A milder degree of TSS may be more
      common. Surgeons who perform sino-nasal surgery should be aware of this disease,
      although certain criteria for definite TSS are absent. Early recognition and
      prompt intervention is important to minimize the morbidity and mortality
      associated with this disease. This paper presents the first reported case of a
      milder degree of TSS after anterior-posterior nasal packing in Thailand. The
      criteria for diagnosis, the pathogenesis, and the management of TSS were
      reviewed.

PMID- 11460953
TI  - Think again about blood transfusion.

PMID- 11460954
TI  - Prevalence estimation of dementia among Thai elderly: a national survey.
AB  - OBJECTIVE: To determine the prevalence of dementia and its associated factors
      among Thai elderly. DESIGN: A one-stage cross-sectional national survey. SETTING:
      National communities in Thailand. SUBJECTS: 4,048 elderly subjects aged 60 and
      above. RESULTS: There were 668 (16.5%) elderly with a CMT score below 15. Among
      these elderly, 132 were dependent as to certain aspects of self-care. According
      to the definition of dementia used in this one-stage survey design (i.e. subjects
      with a low CMT score and self-care dependence), 3.3 per cent of Thai elderly (95%
      confidence interval = 2.7-3.8) were classified as having dementia. After
      adjusting to geographic and municipal area, the prevalence rate was 3.4 per cent
      (95% confidence interval = 2.8-4). Age-specific prevalence rate increased
      dramatically from 1.0 per cent in the 60-64 age-group to 31.3 per cent in the 90+
      age-group. The prevalence rate of dementia among Thai elderly found in this study
      did not differ from the prevalence rates among the elderly in other Asian and
      developed countries. Using a logistic regression analysis, 3 independent factors
      associated with dementia were age, literacy (writing) and geographic area.
      CONCLUSION: With a one-stage survey design for determining the prevalence of
      dementia, the prevalence rate and age-specific prevalence rate among the Thai
      elderly did not differ from those found in other Asian and developed countries.

PMID- 11460955
TI  - Risk factors for dementia and impaired cognitive status in Thai elderly.
AB  - OBJECTIVE: To examine the association of physical and biochemical risk factors
      for dementia and cognitive status in an urban population based Thai elderly.
      MATERIAL AND METHOD: This study was part of an integrated health research project
      from 1997 to 1999. Subjects were 550 elders who lived in a community within 10 km
      from Siriraj Hospital, Bangkok, Thailand. They were 55 years and older. Thai
      mental state examination (TMSE) was applied to all subjects as the screening test
      for dementia. Those who scored less than or equal to 24 out of 30 were
      categorised as having cognitive impairment or suspected of having dementia, and
      they were then examined in detail for the diagnosis of dementia using the DSM IV
      criteria. Blood pressure and body weight were recorded. Blood was drawn for
      biochemical and haematological analysis including the serology for syphilis and
      thyroid function test as the basic screening investigation for dementia.
      Descriptive data, expressed as the mean, standard deviation, Pearson Chi square
      and ANOVA tests were analysed with SPSS 9.0 in the study. RESULTS: Of 550
      subjects, 261 (47.45%) were classified as the normal subjects group, 49 (8.91%)
      as the cognitively impaired group, and 240 (43.82%) as the dementia group. 377
      subjects (68.55%) were female and the distribution of females in each subgroup
      ranged from 63.3-75.5 per cent. The mean age in the normal group was 67.47 +/-
      6.05 years, the cognitively impaired group was 70.14 years and the dementia group
      was 69.63 +/- 9.21 years. Systolic blood pressure (BP), diastolic BP, serum
      cholesterol, SGOT, GGT, serum albumin, haemoglobin, MCHC, neutrophil counts and
      weight were statistically significant factors that were associated with cognitive
      status. Both systolic and diastolic BP were high in the higher cognitive status
      group. Serum albumin, serum cholesterol levels and body weight were also higher
      in the high cognitive status group. CONCLUSION: This study demonstrated an
      association between nutritional status and cognitive status in Thai elderly.
      Poorer nutritional factor in lower cognitive function individuals might explain a
      lower of both systolic and diastolic BP in the dementia subjects compared to the
      healthy subjects.

PMID- 11460956
TI  - Current status of gastric cancer in Thai patients.
AB  - To determine the current status in various aspects of gastric cancer in Thai
      patients, we retrospectively reviewed the records of 119 patients with
      histologically proven gastric cancer in King Chulalongkorn Memorial Hospital
      during the five-year period from 1994 to 1998. There were 72 males (60.5%) and 47
      females (39.5%) with ages ranging from 22 to 91 years (mean age 60.2+/-15.1
      years). Among these, 20 patients (16.8%) were younger than 40 years. The duration
      of symptoms prior to first presentation averaged 20 weeks and dyspepsia and
      weight loss were the most common complaints. Lesion location was lower third in
      40.3 per cent, middle third in 31.9 per cent, upper third in 15.1 per cent and
      entire stomach in 3.4 per cent of patients. Adenocarcinoma was the most common
      histological finding (91.6%), followed by lymphoma and leiomyosarcoma (3.4%
      each). Helicobacter pylori infection was detected in 17 of 25 (68%). The TMN
      staging was as follows: stage II, 5.9 per cent; stage III, 9.2 per cent; and
      stage IV, 68.9 per cent. (the stage was unknown in 16%). The overall 1-year, 2
      year and 5-year survival rates were 51.6 per cent, 17.5 per cent and 4.4 per
      cent, respectively. Management was surgical treatment in 58.9 per cent (total
      gastrectomy 14.5%, subtotal gastrectomy 33.3% and palliative bypass surgery in
      11.1%). Systemic chemotherapy was the primary modality of therapy in 16.8 per
      cent and was adjuvant therapy in 18.5 per cent. The median survival time of
      resectable cases was 1.00+/-0.53 years, significantly longer than that of
      unresectable cases (0.11+/-0.03 years) (p=0.0025). However, the administration of
      chemotherapy did not improve the survival rate. It is concluded that, in
      Thailand, gastric cancer continues to be an important health problem and is
      generally associated with a poor prognosis.

PMID- 11460957
TI  - Neural tube defects: a different pattern in northern Thai population.
AB  - The objective of this descriptive study was to describe the demographic and
      sonographic patterns of fetal neural tube defects (NTDs) in Thai pregnant women.
      The study was conducted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai
      University. The subjects included all pregnancies with diagnosis of fetal neural
      tube defects. Basic clinical data of the subjects was prospectively collected at
      the time of diagnosis for NTDs and followed-up until delivery. Antenatal
      diagnosis was based on sonographic criteria. The results showed that the
      incidence of NTDs was 0.66/1,000 births, however, spina bifida was very rare,
      found in only 0.06/1,000 births, similar to encephalocele. All anencephalic
      fetuses had no concurrent spina bifida, and only a few cases had other associated
      anomalies. Ultrasound was able to diagnose NTDs with very high accuracy. All
      cases of antenatal diagnosis were electively terminated. In conclusion, NTDs in
      the Thai population were rather rare when compared to that of the Europeans and
      spina bifida was extremely rare. The accuracy of antenatal diagnosis of NTDs with
      ultrasound was highly reliable.

PMID- 11460958
TI  - Prevalence of factor V Leiden in Thai blood donors.
AB  - Factor V Leiden was recently found to be the most common cause of familial venous
      thrombosis in the European population. We have studied the prevalence of factor V
      Leiden by DNA analysis among 500 Thai blood donors (male 285, female 215). Their
      ages ranged from 18 to 60 years with a mean of 33 years and 2 months. All of them
      were healthy voluntary blood-donors who met the standard criteria of the American
      Association of Blood Banks. No history of thrombosis was found. The results
      revealed that factor V Leiden was not present among 1,000 chromosomes from Thai
      blood donors. This suggests that factor V Leiden is not the common genetic
      predisposing factor of venous thrombosis in the Thai population as compared to
      the European population.

PMID- 11460959
TI  - Tetanus in adults: a review of 85 cases at Chon Buri Hospital.
AB  - From 1988 to 1999, 85 cases of adult tetanus were admitted to the medical service
      of Chon Buri Hospital. The male to female ratio was 2.2:1. In 50 patients disease
      was severe enough to require paralysis and artificial ventilation. Fourteen
      patients needed diazepam and artificial ventilation but not paralysis; and in
      twenty-one the condition was mild, requiring diazepam only. Eleven patients died,
      all of them had severe grade of tetanus. The mortality rate was 12.9 per cent. In
      70 patients a wound was the source of infection, most of which were minor, often
      receiving no medical attention. No wounds or obvious source of infection could be
      found in 15 patients. Tetanus is a preventable disease. The treatment of tetanus
      is time-consuming and costly and there is still a considerable mortality rate. In
      moderate to severe cases, the patients usually have to spend three to four weeks
      in an intensive care unit.

PMID- 11460960
TI  - Measles antibody in the children in Ubon Ratchathani province.
AB  - Measles is a highly contagious disease, preventable by vaccine. Measles epidemics
      have been dramatically controlled since the introduction of live attenuated
      measles vaccine. Measles antibody is used as an indicator of previous natural
      infection or vaccination, and also as a marker of protective immunity. The
      authors determined measles IgG levels in 1,176 children in Ubon Ratchathani
      province by ELISA from September 1998 to January 1999. Two- hundred and sixty-
      five cases (22.5%) had antibodies below the protective level (< 320 mIU/ml).
      Antibodies were high during the neonatal period, then declined to below the
      protective level at 4-6 months of age, and were negative at age 7-11 months. An
      increase in antibody level after 1 year old might be the result of measles
      immunization at 9-12 months of age, then antibodies decreased to the lowest level
      at 3-5 years after immunization or 4-6 years of age. A second dose of
      immunization will increase the number of children who have antibodies above the
      protective level better than one dose of immunization and it is recommended to
      revaccinate at 4-6 years of age. There was no statistical difference of measles
      antibody between boys and girls in all age groups.

PMID- 11460961
TI  - Loop electrosurgical excision procedure (LEEP) at Maharaj Nakorn Chiang Mai
      Hospital: problems in pathologic evaluation.
AB  - BACKGROUND: Loop electrosurgical excision procedure (LEEP) is widely used in
      diagnosis and management of cervical lesions. Difficulties in histopathologic
      evaluation of LEEP specimens, particularly for the margin status, have been
      reported to be a significant disadvantage of the procedure. METHOD: The
      histologic slides of the specimens from 163 patients who underwent LEEP at
      Maharaj Nakorn Chiang Mai Hospital from August 1995 to November 1997 were
      retrospectively reviewed for the degree of thermal artefact and the margin
      status. Follow-up data after a 6-month-period were correlated with the margin
      status. RESULTS: Thermal artefact was present in all cases (mild 51.5%, moderate
      36.2%, and severe 12.3%). In only one case, histologic diagnosis of the lesion
      was not possible due to severe thermal artefact. Nine cases (5.5%) had non
      evaluable margins due to either thermal artefact (7 cases) or improper
      orientation of fragmented tissue (2 cases). Of 90 cases with subsequent surgical
      specimens, residual diseases were present in 4 of 21 (19.0%) with negative LEEP
      margins, in 31 of 64 (48.4%) with positive margins, and in 4 of 5 (80.0%) with
      non-evaluable margins. CONCLUSIONS: Pathologic evaluation of the specimens from
      LEEP was limited in only a minority of cases. Thermal artefact was not a critical
      disadvantage of LEEP. The positive or negative margin status was correlated with
      the risk of residual disease.

PMID- 11460962
TI  - Therapeutic termination of second trimester pregnancy with vaginal misoprostol.
AB  - OBJECTIVE: To evaluate the efficacy of vaginal misoprostol in therapeutic
      termination of second trimester pregnancy with a live fetus. DESIGN: Prospective
      descriptive study. SETTING: Maharaj Nakorn Chiang Mai Hospital, Department of
      Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University. SUBJECTS:
      Pregnant women meeting the inclusion criteria including 1) pregnancy with a live
      fetus, 2) gestational age of 14-28 weeks, 3) having an indication for therapeutic
      termination, 4) Bishop's score of < or = 4, 5) absence of uterine contraction and
      leakage of amniotic fluid, 6) no previous classical uterine scar and 7) no
      contraindication for misoprostol such as hypersensitivity. INTERVENTION: 400
      microgram misoprostol gel intravagina every 12 hours. MAIN OUTCOME MEASURES: Mean
      induction-delivery time, mean abortion time, maternal side effects. RESULTS:
      Sixty eight pregnant women were recruited into the study. The mean induction
      delivery time was 35.58 +/- 34.13 hours, mean abortion time was 35.80 +/- 34.13
      minutes. Fever was the most common side effect occuring in about two-third of the
      patients, but no serious maternal complication was observed. CONCLUSION: 400
      microgram vaginal misoprostol is effective for therapeutic termination of second
      trimester pregnancy with no serious side effects. However, the response to this
      treatment was markedly varied from patient to patient.

PMID- 11460963
TI  - Short fetal acoustic stimulation test for rapid antepartum assessment of fetal
      well-being.
AB  - Short fetal acoustic stimulation test (FAST) was prospectively studied in 604
      high risk pregnancies after 28 weeks of gestation. Fetal heart rates were
      recorded 3 minutes before and 5 minutes after fetal acoustic stimulation. The
      results of the tests performed within a week of delivery were compared with
      perinatal outcomes. Reactive response to short FAST occurred in 597 cases (98.8%)
      while nonreactive response was found in 7 cases (1.2%). Nine fetuses were
      considered poor outcomes. The sensitivity, specificity, positive predictive
      value, negative predictive value and accuracy of short FAST to predict poor fetal
      outcomes were 66.7, 99.8, 85.7, 99.5, and 99.3 per cent, respectively. Short FAST
      has high specificity, negative predictive value and accuracy for prediction of
      poor perinatal outcome. This rapid test should be used as a screening method for
      antepartum assessment of fetal well-being in a busy antenatal clinic.

PMID- 11460964
TI  - Posterior C1-C2 transarticular screw fixation for Atlanto-axial instability.
AB  - The objective of this study was to reveal that the treatment of C1-C2 instability
      by transarticular C1-C2 screw fixation with bone graft has a better result than
      conventional sublaminar wiring with bone graft by Gallie's technique. This
      technique, proposed by Magerl and Semann in 1987, produces a rigid three points
      fixation resulting in maximal bone fusion rate and does not require an orthosis
      post-operatively. This technique is performed in patients with fractured lamina
      of C1 or in patients who need a laminectomy of C1 for spinal cord decompression.
      This study revealed 10 patients having C1-C2 instability who were operated on by
      transarticular C1-C2 screw fixation with bone graft. No complication was
      encountered. No screw and bone graft slipping were noted. The patients were
      improved clinically and the average follow-up period was 7.7 months. There were 2
      cases which had previously been operated on for sublaminar wiring but the
      operation was unsuccessful because there was a fractured lamina of C1. Both
      patients were sent to Prasat Neurological Institute & Hospital for transarticular
      C1-C2 screw fixation. Another 2 cases were operated on for sublaminar wiring with
      bone graft. The follow-up X-ray of both cases disclosed a displacement of C1-C2.
      Lost of C1 lamina was found in one case and there was slipping of wire in another
      case, because of this the patients were re-explored for transarticular C1-C2
      screw fixation with bone graft. The conclusion is, this technique of
      transarticular C1-C2 screw fixation, is the best surgical treatment for C1-C2
      instability, in the hands of experienced surgeons with an excellent knowledge of
      anatomy.

PMID- 11460965
TI  - Chromosomal analysis of "failed-fertilized" human oocytes resulting from in-vitro
      fertilization and intracytoplasmic sperm injection.
AB  - To evaluate the incidence of chromosomal abnormalities in "failed-fertilized"
      oocytes derived from in-vitro fertilization (IVF) and intracytoplasmic sperm
      injection (ICSI) procedure, a cytogenetic analysis was performed on 164 IVF and
      64 ICSI oocytes. One hundred and eleven (67.7%) of the IVF and 56 (87.5%) of the
      ICSI oocytes were successfully karyotyped. Of 111 IVF oocytes, 73 (65.8%)
      exhibited normal haploid and 38 (34.2%) were abnormal. The abnormalities included
      25 aneuploid (22.5%) (7 hyperhaploid and 18 hypohaploid), 11 diploid (9.9%) and 2
      structural anomalies (1.8%). Of 56 ICSI oocytes, 52 (92.8%) were normal haploid
      and only 4 (7.2%) were aneuploid, with 2 hyperhaploid and 2 hypohaploid. The
      sperm nuclei were observed in 43 IVF oocytes (38.7%), composed of 38 (34.2%)
      premature chromosome condensation (PCC) and 5 (4.5%) decondensed sperm heads.
      Evidence of successful sperm delivery was found in all 56 ICSI oocytes; 25.0 per
      cent (14/56) showed PCC, 17.9 per cent (10/56) showed decondensed sperm heads,
      and 57.1 per cent (32/56) showed intact sperm heads. This study suggested that
      about one-third of unfertilized oocytes exhibited chromosomal abnormalities. The
      difference of aneuploidy between IVF and ICSI oocytes needs further studies
      analysing a larger number of oocytes.

PMID- 11460966
TI  - Effect of oral estriol on urogenital symptoms, vaginal cytology, and plasma
      hormone level in postmenopausal women.
AB  - OBJECTIVE: To evaluate the effects of oral estriol on urogenital symptoms,
      vaginal cytology, and plasma follicle stimulating hormone (FSH) and estradiol
      level in postmenopausal women with urogenital symptoms. METHOD: Twenty-eight
      postmenopausal women with urogenital symptoms who volunteered to participate in
      this study received 2 mg of oral estriol daily for 12 weeks. The urogenital
      symptoms, vaginal cytology, and plasma hormone level before and after treatment
      were analysed using paired t-test. RESULTS: The genital and urological symptoms
      improved (P < 0.05) after treatment in all subjects. The vaginal cytology showed
      estrogenic effect on the karyopyknotic index and maturation value. There was a
      significantly (P < 0.05) higher level of plasma estradiol after 12 weeks of
      treatment. However, the difference of plasma FSH level before and after treatment
      was not statistically significant. CONCLUSION: The daily oral estriol had a
      positive effect on the urogenital symptoms and vaginal cytology. The plasma
      estradiol increased after 12 weeks of treatment but the plasma FSH did not
      change.

PMID- 11460967
TI  - Factors affecting chemistry of reduction-mediated 99mTc-labelling of monoclonal
      antibodies and polyclonal human immunoglobulins.
AB  - In developing a new method for preparing a radiopharmaceutical for clinical
      investigation, a thorough understanding of reaction stoichiometry is crucial in
      optimizing the labelling chemistry. Factors determining labelling efficiency of
      the 2-mercaptoethanol (2-ME)-mediated 99mTc-labelling of antibody molecules were
      elucidated using anti-tumor monoclonal antibodies of different IgG subclasses
      (i.e. IOR-CEA(IgG1), M170(IgG1), 3F8(IgG3) and EMD (IgG2a)) and polyclonal human
      immunoglobulins (Sandoglobulin). Antibodies which were sensitive to 2-ME
      reduction (i.e. required 500-1000 molar excess of 2-ME) could tag 99mTc with high
      efficiency since they possessed abundant reactive sites (i.e. sulfydryl groups)
      for 99mTc binding. Reduction sensitivity of antibodies was unlikely to be
      affected by IgG subclass and could be rated as follows: Sandoglobulin > IOR-CEA >
      3F8 > M170 > EMD. Concentrations of the reduced antibodies for effective
      labelling appeared to be related to the reduction sensitivity, i.e. 0.2, 0.4 and
      0.6 mg/ml were required for labelling of IOR-CEA, 3F8 and M170 respectively. In
      addition, susceptibility to 2-ME reduction seemed to reflect the rate of antibody
      labelling. For 2-ME resistant molecules, i.e. M170 and EMD, successful labelling
      could be achieved by using a slow 99mTc reducing agent such as SnCl2 instead of
      SnF2 which reacted more rapidly. Since 2-ME generates reactive sulfhydryl groups
      that are distal to antigen binding sites, the immunoreactivity of the modified
      antibody was not affected by the effect of reduction.

PMID- 11460968
TI  - Efficacy and safety of gabapentin as an add-on therapy in refractory partial
      epileptic patients.
AB  - The study on the efficacy and safety of gabapentin as an add-on therapy trial was
      performed in 10 refractory partial seizure cases at Prasat Neurological
      Institute, Thailand from September 1996 to July 1998. This was an open-labeled
      titration dose of gabapentin starting at 600 mg/day add-on to the previously
      prescribed conventional antiepileptic drugs (AEDs). In cases that seizures could
      not be controlled, gabapentin dose was increased by 300 mg per day every two
      weeks until the total dose of 3,000 mg or until the side effects became
      intolerable. The result revealed that gabapentin reduced frequency, duration and
      severity of seizures and also improved the patients' activities of daily living
      (ADL) even at the minimum dose of 600 mg. The optimal dose of gabapentin was in
      the range of 600 to 1,200 mg per day. Seven patients were seizure free at the end
      of the study. There were some precipitating factors that interfered with the
      efficacy of gabapentin in some patients such as stress, menstruation, fever, and
      alcohol intake. Weight gain, somnolence, nystagmus, and dizziness were the major
      adverse events in these patients, whereas ataxia, tremor, and diplopia were found
      with gabapentin in a dose higher than 1,800 mg/day. These adverse events were
      mild and transient. No patients withdrew from the study due to adverse drug
      reactions. In addition, gabapentin did not alter conventional AED blood level and
      routine laboratory parameters. In conclusion, gabapentin was effective and well
      tolerated as an add-on therapy in refractory partial epileptic Thai patients.

PMID- 11460969
TI  - Nasolacrimal duct injury from microscopic sinus surgery: preliminary report.
AB  - Nasolacrimal duct injury is a well established complication of functional
      endoscopic sinus surgery. In 1992, Bolger reported an incidence of nasolacrimal
      duct injuries in endoscopic sinus surgery of up to 15 per cent, but there is no
      documentation in microscopic sinus surgery. Fluorescein instillation into the
      lacrimal system via the punctum was done to determine the incidence of
      nasolacrimal duct injuries in 16 patients who underwent 32 microscopic sinus
      procedures. Only one patient exhibited nasolacrimal duct injury intraoperatively
      on the left side (0.3%). He had complete healing of the nasolacrimal duct at 2
      months and no postoperative epiphora developed.

PMID- 11460970
TI  - The accuracy of bone mineral density at distal radius on non-forearm osteoporosis
      identification.
AB  - The accuracy of BMD at distal radius was evaluated in terms of sensitivity,
      specificity, false negative, false positive, predictive value of a positive
      (osteoporosis) and a negative (normal) test for non-forearm osteoporosis. 278
      women (150 osteoporotic and 128 normal) were measured for both distal radius bone
      mineral density (BMD) using Panasonic (DXA-70) dual energy X-ray absorptiometry
      (DEXA) and non-forearm BMD using Hologic (QDR-4500) DEXA on the same day. The
      results showed that mean age, menopause age, height and weight in the
      osteoporotic group were not different from the healthy group (p=0.168, 0.091,
      0.274 and 0.097, respectively). Mean BMD of both distal radius and lumbar spine
      in the normal women was significantly higher than that in the osteoporotic group
      (p<0.001, = 0.002, <0.001, respectively). While mean BMD of the hip, femoral neck
      and Ward's triangle in both groups was not different (p = 0.330, 0.874, 0.847,
      respectively). The sensitivity of BMD of the right radius was very high (90.00
      95.45%) and specificity was moderately high (53.85-73.68%). While false negative
      (4.55-10.00%) was less than false positive (26.32-46.15%). The accuracy of right
      radius BMD when compared with spine, hip, femoral neck and Ward's triangle was
      82.35, 66.66, 80.00 and 86.49 per cent, respectively. The sensitivity (85.00
      96.67%), specificity (57.69-81.58%), false negative (3.33-15.00%) and false
      positive (18.42-42.31%) of left radius BMD had the same trend as right radius
      BMD. Accuracy of the left radius when compared with non-forearm BMD was 88.24,
      66.67, 75.71 and 86,49 per cent, respectively. The predictive value of right
      radius osteoporosis was 73.68, 47.37, 77.78 and 89.66 per cent for detecting
      osteoporosis at spine, hip, femoral neck and Ward's triangle, respectively. The
      predictive value of normal right radius BMD was 93.33, 92.86, 87.50 and 75.00 per
      cent, respectively for normal non-forearm BMD. Moreover, the predictive value of
      left radius osteoporosis for identifying spinal, hip, femoral neck and Ward's
      triangle osteoporosis was (80.56, 47.22, 77.55 and 91.07%, respectively) and the
      predictive value of normal left radius BMD for identifying normal BMD at non
      forearm sites (96.88, 90.00, 71.43 and 72.22%, respectively) was revealed. It
      indicated that forearm DEXA provides adequate accuracy for in vivo determination
      of spinal, femoral neck and Ward's triangle osteoporosis. However, there was
      inadequate accuracy and very low predictive ability for identifying hip
      osteoporosis.

PMID- 11460971
TI  - The effectiveness of lumbosacral corset in symptomatic degenerative lumbar spinal
      stenosis.
AB  - Lumbosacral corset is a spinal support widely used for patients suffering from
      low back pain due to various conditions. To evaluate the effectiveness of the
      corset in symptomatic degenerative lumbar spinal stenosis, twenty one patients
      (mean age 62.5 +/- 5.2 years) with neurogenic claudication (mean onset 9.0 +/-
      9.3 months) were recruited for and completed a self controlled comparative study
      (with and without a corset). Quantitative and qualitative assessment in terms of
      walking distance and pain score (0-10 point visual analog scale) in daily
      activities respectively, compared between wearing and not wearing the corset were
      measured. The outcome of the study showed statistically significant improvement
      in walking distance (393.2 +/- 254.0 m and 314.6 +/- 188.8 m) and decrement of
      pain score in daily activities (4.7 +/- 1.4 and 5.9 +/- 1.0) with and without
      corset dressing respectively. This result supports the positive effect of the
      lumbosacral corset in pain relief and functional improvement of the degenerative
      lumbar spinal stenosis condition.

PMID- 11460972
TI  - Comparative study between the classical Westergren and the new sealed vacuum
      extraction methods for erythrocyte sedimentation rate determination.
AB  - A comparative study between the classical Westergren and the new sealed vacuum
      extraction methods for erythrocyte sedimentation rate determination was performed
      on 80 individual subjects. The comparison-of-methods plot sealed vacuum
      extraction method (X) vs Westergren method (Y) gave a least square linear
      regression equation of Y = 1.001 X + 0.03 (r = 0.99) and precision analysis gave
      a coefficient of variation below 3 per cent. Compared to the classical method,
      the sealed vacuum extraction method was easy to use, showed acceptable precision
      and reduced biohazard risk to the practitioner, therefore, it was suitable for a
      laboratory setting with a high rate of blood-borne infectious diseases such as
      Thailand.

PMID- 11460973
TI  - Acute polyradiculoneuropathy with cerebrospinal fluid eosinophilia.
AB  - A 60-year-old woman who presented with quadriparesis, dysarthria and dysphagia
      after acute febrile illness was reported. Neurological examination and
      electrodiagnostic study were compatible with acute polyradiculoneuropathy. Lumbar
      puncture revealed cerebrospinal fluid eosinophilia. Her muscle power improved
      after supportive treatment.

PMID- 11460974
TI  - Peripheral primitive neuroectodermal tumor with neuronal and glial
      differentiation: report of a case arising in suprarenal region.
AB  - It is well known that embryonal neuroectodermal tumors of the central nervous
      system (CNS) not infrequently display varying amount of neoplastic cells
      acquiring glial differentiation. In contrast, glial differentiation rarely occurs
      in primitive neuroectodermal tumors outside the CNS being documented in less than
      ten cases. The author presents herein a case of peripheral primitive
      neuroectodermal tumor with prominent glial differentiation identified by the
      presence of glial fibrillary acidic protein (GFAP) arising in the right
      suprarenal region of a 32-year-old man, histologically indistinguishable from an
      ordinary neuroblastoma.

PMID- 11460975
TI  - A report case of Cyclospora and Cryptosporidium mixed infection in a HIV-negative
      child in Thailand.
AB  - The first case of cyclosporosis in a non HIV-infected child in Thailand, co
      infected with Cryptosporidium, was reported. The patient was a 3 year-old
      malnourished orphan who presented with fever, abdominal distension and relapsing
      diarrhea. There was no leukocyte in her stool, however, numerous Cyclospora and
      Cryptosporidium oocysts were identified by modified acid-fast staining. The
      illness was cured by co-trimoxazole and fluid therapy. More coccidial infections
      in Thailand may be detected if modified acid-fast staining is routinely
      performed.

PMID- 11460976
TI  - Treatment of invasive fungal sinusitis with liposomal amphotericin B: a report of
      four cases.
AB  - Invasive fungal sinusitis increasingly causes significant morbidity and mortality
      in immunocompromised patients. It is difficult to treat. Despite standard
      treatment by surgical debridement and intravenous amphotericin B, morbidity and
      mortality remain high. Conventional amphotericin B is the standard drug but its
      use is limited by dose-related nephrotoxicity and infusion-related acute
      toxicity. Liposomal amphotericin B has proven to be as effective as conventional
      amphotericin B with less nephrotoxicity and infusion reaction. We report four
      cases of invasive fungal sinusitis who were treated with liposomal amphotericin B
      after having severe side effects from conventional amphotericin B. There were two
      cases of mucormycosis and two cases of aspergillosis. All patients had diabetes
      millitus. One patient had systemic lupus erythematosus and another was receiving
      immunosuppressive drugs after kidney transplantation. All cases needed multiple
      operations for sinus surgery. Two cases had acute reaction to amphotericin B
      infusion, one had active lupus nephritis with renal insufficiency, and one was
      considered treatment failure from amphotericin B. The patients received liposomal
      amphotericin B at the total doses of 4.55-8.85 g. Two cases of mucormycosis were
      considered to be successfully treated. In cases of aspergillosis, one was
      considered improved and another one with immunocompromised status died with
      active disease. From our experience, surgery is the main treatment for patients
      with invasive fungal sinusitis and liposomal amphotericin B is an effective
      alternative drug for adjuvant medical treatment. However, the degree of
      immunosuppression of the patients, the extension of fungal sinusitis and perhaps
      the species of fungus are important factors determining the clinical response.

PMID- 11460977
TI  - Limb-body wall complex, report of 2 cases with their quintessence in prenatal
      diagnosis.
AB  - Limb-body wall complex is a complicated fetal malformation with the essential
      features of: 1) exencephaly/encephalocele with facial clefts, 2) thoraco- and/or
      abdominoschisis, and 3) limb defect. The diagnosis was based on two of three of
      the above features. We report 2 cases of limb-body wall complex. The first case
      had thoraco-abdominal and limb anomalies while the other had abdominal wall, limb
      and neuro-facial anomalies. Both cases were diagnosed prenatally by
      ultrasonography. They were terminated by medical induction. Chromosome studies
      were evaluated for academic purposes. Autopsies were done to confirm diagnosis.
      Aspects of their varieties of clinical features, differences in differential
      diagnosis, and pitfalls in prenatal diagnosis were discussed.

PMID- 11460978
TI  - Doctor in the 30 baht era: ethics vs policy.

PMID- 11460979
TI  - Pediatric heart transplantation: improving results in high-risk patients.
AB  - Our institutional experience with 68 pediatric patients undergoing cardiac
      transplantation was reviewed to determine the impact of unconventional donor and
      recipient management protocols implemented to extend the availability of this
      therapy. The introduction of donor blood insulin cardioplegia was associated with
      a significant improvement in patient and graft survival. Among 63 ABO-matched
      transplant procedures, both the patient and graft loss rate were significantly
      lower (by multivariable analysis) with the use of the donor blood insulin
      cardioplegia versus conventional cardioplegia, despite significantly longer
      ischemic times in the former group. Twenty-three (33.8%) patients were deemed at
      ultra-high risk: eight of 11 patients with cardiomyopathy transplanted following
      ECMO support survived without major sequelae; three of four additional patients
      survived early retransplantation. Ten patients underwent intentional ABO
      incompatible transplantation under a protocol of plasma exchange on bypass. There
      were two early deaths because of nonspecific graft failure and respiratory
      complications with mild vascular rejection, and one late death because of
      lymphoma. Among seven surviving ABO-incompatible patients followed up to 31
      months, there have been no episodes of humoral rejection despite development of
      antidonor blood group antibodies in A to O, but not B to O, mismatches. The
      results with pediatric cardiac transplantation continue to improve as a result of
      changes in both surgical and medical protocols permitting salvage of patients
      conventionally considered at high risk or nontransplantable.

PMID- 11460980
TI  - Lung transplantation in infants.
AB  - Lung transplantation is an accepted mode of therapy for patients with end-stage
      pulmonary vascular or parenchymal diseases. To date, application to the pediatric
      age population in general, and the infantile group in particular, has been
      limited both in terms of number of transplants and follow-up thereafter. We
      performed our first transplant in an infant in 1993 and have performed 30 lung
      transplants in children under 1 year of age subsequent to that. This chapter will
      review the experience to date including indications for transplantation, post
      transplant management, complications, and long-term follow-up.

PMID- 11460981
TI  - Immunobiology of cardiac allograft and xenograft transplantation.
AB  - Heart transplantation has been performed clinically for four decades, and has
      become the standard of care for end-stage heart disease. Our understanding of the
      immunobiology of transplantation has made tremendous strides, but our knowledge
      still lags behind the clinical use. As a result, nonspecific immunosuppression
      remains the standard therapy. This chapter is a review of our present knowledge
      of the immunobiology of allotransplantation and xenotransplantation with emphasis
      on antigen presentation, costimulation, and T-cell activation in the context of
      transplantation. The molecular events of T-cell activation, with some emphasis on
      the sites of action of present day immunosuppression, are reviewed. Basic aspects
      of immunosuppression are reviewed elsewhere in this edition. Given the paucity of
      allografts, xenografts are being considered as an alternative donor source. This
      being the case, cellular and humoral response to xenografts is considered and
      contrasted with our understanding of allograft immunity. Basic mechanisms of
      tolerance are discussed, with examples of experimental tolerance induction in
      small and large animals. A brief description of special considerations for the
      immunology in human neonate/infant recipients is mentioned. Understanding the
      immunobiology of transplantation is key to making decisions regarding heart
      transplant recipients today, in addition to developing better protocols and the
      induction of tolerance in the future.

PMID- 11460982
TI  - Immunology of pediatric heart transplantation: a clinical update.
AB  - In the last decade, tremendous advances in our understanding of immune responses
      to solid organ allografts have been realized. These advances are now resulting in
      improved management of patients. It is hoped that these advances may soon lead to
      successful tolerance induction, relieving the patient of the lifetime burden of
      immunosuppressive therapy. The molecular and cellular mechanisms involved in
      acute and chronic allograft rejection are reviewed in detail elsewhere in this
      annual. This review will focus on the immunologic aspects of clinical heart
      transplantation, with emphasis on recent advances in knowledge in the pediatric
      population. Risk factors for detection, prevention, and treatment of acute and
      chronic rejection are discussed. The immunologic burden of nonspecific
      immunosuppression (infection, post-transplant lymphoproliferative disorders, and
      malignancy) is reviewed. The prospects for achievement of donor-specific
      tolerance in the clinic are discussed.

PMID- 11460983
TI  - Double-Switch operation for congenitally corrected transposition.
AB  - Double-switch operation was performed in 76 patients with congenitally corrected
      transposition of the great arteries at the Heart Institute of Japan, Tokyo
      Women's Medical University. Detailed surgical techniques of Mustard and Senning
      procedures for inlet switch, as well as arterial switch operation, pulmonary
      reconstruction by direct right ventricular-pulmonary arterial anastomosis, and
      external conduit repair for outlet switch are described in detail.

PMID- 11460984
TI  - Collaborative interventional and surgical strategies in the management of
      congenital heart lesions.
AB  - In the last 15 years the development of catheter-directed percutaneous therapies
      have improved the delivery of care to children with congenital heart lesions.
      Paralleling these advances, enhanced surgical techniques are now applied to
      complex cardiac lesions previously thought to be inoperable. This chapter
      outlines several treatment strategies which utilize surgical and catheter-based
      algorithms to address congenital heart disorders.

PMID- 11460985
TI  - Video-assisted endoscopy for congenital heart repair.
AB  - Endoscopic imaging techniques can be used to enhance visualization of and access
      to remote intracardiac structures to improve congenital heart repairs. Database
      storage of these images builds a foundation for retrospective analysis of
      surgical failures and clinical correlations with other imaging techniques. The
      images also function as an educational tool for patients, families, and the
      cardiac team. Combining cardiac endoscopic imaging with interventional
      catheterization techniques has created a group of hybrid procedures, extending
      the capabilities of both the surgeon and the interventional cardiologist. This
      synergy has the potential to decrease therapeutic trauma.

PMID- 11460986
TI  - Reducing the trauma of congenital heart surgery.
AB  - Techniques to reduce surgical trauma for congenital heart repairs continue to
      evolve in tandem with advances in the more conventional protection strategies.
      The concept of chest wall protection has been increasingly accepted as an
      important standard for congenital heart surgeons, as long as neuroprotection,
      myocardial protection, and operative precision are not adversely affected.
      Unfortunately, it is difficult to measure chest wall trauma, making it difficult
      to evaluate the efficacy of minimally invasive techniques. Efforts to reduce
      surgical trauma are advancing on multiple fronts. Many extracardiac repairs are
      being performed thoracoscopically, with excellent results. Intracardiac
      procedures can be performed through smaller incisions. Full sternotomy is giving
      way to a variety of sternal-sparing incisions for open-heart repairs, usually
      using direct visualization. Operative strategies to avoid or minimize the effects
      of cardiopulmonary bypass have emerged. And recently, hybrid procedures,
      utilizing a combination of transcatheter and minimally invasive techniques, are
      creating new therapeutic options for the congenital heart team.

PMID- 11460987
TI  - Diagnosis, natural history, and outcome of fetal heart disease.
AB  - Advances in the prenatal diagnosis of heart disease have improved accuracy in the
      evaluation of structural heart lesions, dysrhythmia mechanisms, and functional
      pathology and will lead to better perinatal management and counseling. Additional
      technical advances will lead to earlier diagnosis, perhaps even during embryonic
      development. Newer developments, including the transumbilical and transuterine
      approaches, may make antenatal intervention possible and safer for a larger
      number of affected pregnancies.

PMID- 11460988
TI  - Considerations in the appraisal of mortality associated with congenital cardiac
      lesions.
AB  - While great improvements have been made, mortality related to congenital cardiac
      lesions continues to be of primary concern. Mortality can be considered from in
      depth retrospective analysis of the individual case, from clinical studies
      seeking to define risk and associated factors, and from studies designed to
      determine institution and operator-specific variations. The analysis of mortality
      is complex, given that the risk from an index event (eg, birth, operation) is
      constantly changing in a time-dependent manner, and that associated factors may
      also change over time as well. In some instances, patients may be at risk for
      other outcomes that may compete with mortality. As mortality lessens with
      advances in technology and clinical care, large multi-institutional studies
      become necessary to provide adequate statistical power to determine risk and
      associated factors.

PMID- 11460989
TI  - Fetal cardiac intervention and surgery.
AB  - Fetal echocardiography has changed our understanding of congenital heart disease
      by allowing us to diagnose and observe the malformed human heart within weeks of
      primary morphogenesis. Serial echocardiographic studies have shown that some
      complex heart malformations result from relatively simple primary lesions that
      occur early during heart development and may be amenable to an in utero
      intervention aimed at altering abnormal growth patterns. Although fetal cardiac
      intervention or surgery does not presently exist as a realistic therapeutic
      option in the management of critical congenital heart disease, progress in
      several areas of investigation give merit to the concept and future potential of
      in utero cardiac repair.

PMID- 11460990
TI  - Cardiac surgery for premature and low birth weight neonates.
AB  - Congenital heart defects in low birth weight infants are typically managed with
      supportive therapy or palliative surgery and definitive repair is delayed.
      However, the morbidity of this approach has been shown to be high. At the
      University of California San Francisco, our approach to these infants has been
      one of complete repair in the neonatal period or as early as possible. Since
      1992, 116 neonates and infants under 2,500 g underwent complete repair of simple
      and complex cardiac defects using cardiopulmonary bypass and circulatory arrest
      was avoided in the majority. Actuarial survival was 80% at 1 year. Noncardiac
      abnormalities contribute significantly to perioperative and late morbidity and
      mortality. Reintervention rates are comparable to other neonates. Our data
      suggests that complete repair of simple and complex congenital heart defects can
      be performed safely and effectively in premature and low birth weight infants.

PMID- 11460991
TI  - Techniques to avoid circulatory arrest in neonates undergoing repair of complex
      heart defects.
AB  - Advances in cardiopulmonary bypass and cardiac surgical techniques have
      tremendously improved the outlook for children born with congenital heart
      defects. However, cardiopulmonary bypass, hypothermia, and circulatory arrest are
      all unphysiologic states and are associated with some morbidity, and the most
      significant are neurologic sequelae, which can be subtle or devastating.
      Circulatory arrest, often used as an adjunct to deep hypothermia, is a major
      contributing factor to the neurologic complications after cardiopulmonary bypass.
      In the last decade, techniques to avoid circulatory arrest have been introduced
      with a substantial decrease in neurologic sequelae.

PMID- 11460992
TI  - Late results of the Rastelli operation for transposition of the great arteries.
AB  - The Rastelli operation, first performed in 1968, was developed for repair of
      transposition of the great arteries with associated ventricular septal defect and
      severe pulmonary stenosis. This operation includes placement of an intracardiac
      baffle to direct left ventricular blood to the aorta and an extracardiac valved
      conduit to establish continuity between the right ventricle and the pulmonary
      arteries. Over the last 3 decades, the Rastelli operation has been performed with
      a progressive decline in early mortality, and it remains the preferred repair for
      transposition, ventricular septal defect, and severe fixed valvular or
      subvalvular pulmonary stenosis. This chapter examines the late results of our 33
      year experience with the Rastelli operation and describes our operative
      technique.

PMID- 11460993
TI  - Management of transposition of the great arteries with single coronary artery.
AB  - Approximately 5% of patients with transposition of the great arteries have a
      single coronary artery. In the early years of the arterial switch procedure a
      single coronary artery was associated with an increased risk of mortality. This
      was particularly true for the most common type of single coronary artery in which
      there is a right posterior ostium giving rise to a right coronary artery that
      passes to the right atrioventricular groove and a left coronary artery that
      passes posterior to the pulmonary artery. An understanding of the mechanisms by
      which this coronary pattern increases the risk of mortality has led to
      neutralization of this risk factor. The risk of late reintervention after an
      arterial switch with single coronary artery is increased with a single left
      posterior ostium with the right coronary passing anterior to the aorta. The
      mechanism remains unclear.

PMID- 11460994
TI  - The bidirectional cavopulmonary shunt for hypoplastic left heart syndrome.
AB  - The use of the bidirectional cavopulmonary shunt has had a favorable effect on
      the outcome of surgery for hypoplastic left heart syndrome. In this chapter, the
      physiology, indications, and technical aspects are discussed, along with comments
      regarding postoperative management and outcome.

PMID- 11460995
TI  - Transposition complexes with systemic obstruction.
AB  - The arterial switch operation is currently the procedure of choice for
      transposition of the great arteries and double-outlet right ventricle with
      subpulmonary ventricular septal defect. While the results of surgical repair have
      improved tremendously in recent years, the presence of associated lesions
      continues to make this a surgically challenging malformation. The association of
      these so-called transposition complexes with systemic obstruction has recently
      received increased attention. Systemic obstruction may occur at the subaortic
      level, in the aortic arch, or at both levels. Valvar aortic stenosis or atresia
      is extremely rare. Resection of hypertrophied muscle bundles with or without
      pericardial patch augmentation is frequently enough to deal with obstruction at
      the subaortic level, which becomes the subpulmonary area following arterial
      switch operation. Aortic arch obstruction associated with intracardiac defects
      has traditionally been addressed with a staged approach, dealing first with the
      arch obstruction followed later by intracardiac repair. The results with this
      approach have been disappointing. At the Montreal Children's Hospital, we have
      obtained superior results using a single-stage approach. Therefore, we have
      advocated the use of pulmonary homograft patch aortoplasty for aortic arch
      reconstruction at the time of intracardiac repair to completely remove any
      anatomic afterload. Since 1989, in 22 consecutive patients undergoing single
      stage anatomic repair of transposition complexes associated with aortic arch
      obstruction, we have had no early deaths, one late death of a noncardiac cause,
      and one recoarctation requiring balloon dilatation. In the last 2 years, we have
      been able to perform all our aortic arch reconstructions avoiding the use of
      circulatory arrest.

PMID- 11460996
TI  - Two-Ventricle repair for hypoplastic left heart syndrome.
AB  - Hypoplastic left heart syndrome encompasses a spectrum of structural cardiac
      malformations characterized by severe underdevelopment of the structures in the
      left heart-aorta complex. The severe end of the spectrum consists of aortic
      atresia and mitral atresia, whereas at the mild end patients have aortic valve
      and mitral valve hypoplasia without intrinsic valve stenosis, recently described
      as hypoplastic left heart complex. These patients may be candidates for
      biventricular repair. Since November 1988, 12 of 13 patients (92%) with
      hypoplastic left heart complex have undergone two-ventricle repair and one
      patient the Norwood operation. Median age at surgery was 7 days (5 to 45 days)
      and median weight was 3.59 kg (2.6 to 4.3 kg). Biventricular repair consisted of
      pulmonary homograft patch aortoplasty of the aortic arch and ascending aorta and
      closure of the interatrial and interventricular communications. The left heart
      was able to support the systemic circulation in 11 of 12 patients undergoing
      biventricular repair (92%). The early mortality was two patients (15.4%). The
      mean follow-up was 67 months (range, 11 months to 133 months). There was one late
      death at 39 months. Reoperations were necessary in four patients for left
      ventricular outflow tract obstruction and in two patients for recurrent
      coarctation. We have successfully achieved biventricular repair in most patients
      with hypoplastic left heart complex, a subset of patients with hypoplastic left
      heart syndrome. Reoperation, particularly for left ventricular outflow tract
      obstruction, appears likely. Finally, with increased experience, predictive
      criteria for the feasibility and optimal outcome of biventricular repair will be
      more accurately defined.

PMID- 11460997
TI  - Extracorporeal life support in heart and lung transplantation.
AB  - Extracorporeal life support is a technology that is being increasingly used to
      support children with cardiac and respiratory failure who fail conventional
      measures. Both extracorporeal membrane oxygenation and ventricular assist devices
      have been used in cardiac failure with the opportunity to support patients who
      fail repair of congenital heart disease and in primary myocardial disease.
      Outcomes in the latter are superior to the surgical patients which has lead to
      increasing use of extracorporeal life support as a bridge to transplantation.
      Experience with membrane oxygenation as a support mode after lung transplantation
      is limited to adult series with similar outcomes.

PMID- 11460998
TI  - Abrogation of tumor necrosis factor-alpha converting enzyme inhibits embryonic
      lung morphogenesis in culture.
AB  - TNF-alpha converting enzyme (TACE)-mediated cell surface protein ectodomain
      cleavage constitutes an important cellular regulatory mechanism during mammalian
      lung development. Herein, we have found that TAPI, a synthetic inhibitor of TACE,
      inhibits embryonic mouse lung branching morphogenesis in culture. To further
      investigate the biological significance of TACE as a shedding enzyme during early
      lung organogenesis, we have devised an antisense oligonucleotide to specifically
      block endogenous TACE gene expression at both transcriptional and translational
      levels in embryonic mouse lung explant culture. Addition of TACE antisense
      oligonucleotide resulted in a concentration-dependent reduction in lung branching
      morphogenesis in culture, whereas both scrambled and sense control
      oligonucleotides showed no adverse effects on lung growth. Furthermore, both
      aquaporin-5 (Aqp5) and surfactant protein-C (SP-C) mRNA expression and protein
      immunoreactivity were significantly inhibited in cultured mouse lungs treated
      with TACE antisense oligonucleotide, indicating defective epithelial cell
      differentiation in embryonic lungs with decreased TACE expression. TACE is known
      to be involved in the proteolytic release of TGF-alpha, an EGF family stimuli
      critical for lung growth and maturation. We therefore tested the possibility that
      a lack of diffusable TGF-alpha, due to TACE deficiency, contributes to the
      inhibitory lung morphogenesis in the presence of TACE antisense oligonucleotide
      in lung culture. Soluble TGF-alpha, when included in the lung culture, rescued
      the TACE antisense oligonucleotide-treated lungs from inhibition of both lung
      branching morphogenesis and lung epithelial cell differentiation, suggesting an
      impaired release of circulating regulators necessary for lung development in the
      absence of TACE gene expression. Our findings provide evidence that TACE-mediated
      membrane protein shedding is indispensable for normal lung branching
      morphogenesis and cytodifferentiation, probably through regulating the
      availability of positive cytokines/growth factors essential for lung
      organogenesis such as TGF-alpha.

PMID- 11460999
TI  - Formation of retinal pigment epithelium in vitro by transdifferentiation of
      neural retina cells.
AB  - Chick embryonic neural retina (NR) dedifferentiates in culture and can
      transdifferentiate spontaneously into retinal pigment epithelium (RPE). Both,
      primary RPE and transdifferentiated RPE (RPEt), are characterized by
      pigmentation, expression of RPE-specific protein, eRPEAG and lack of expression
      of the neural cell adhesion molecule, NCAM. In contrast, NR cells are unpigmented
      and express NCAM but not eRPE(AG). Functionally, both primary RPE and the RPEt
      cells display a pH(i) response to bFGF, which is different from that of the NR.
      We used these characteristics to distinguish cell types in primary cultures of
      chick NR and follow the changes in phenotype that occur during
      transdifferentiation. We show that the RPEt forms as small "islands" in the
      packed regions of the primary, "mother" NR cell sheets, in a stochastic process.
      Because of a small number of cells involved in the initiation of the
      transdifferentiation we refer to it as a "leader effect" to contrast it with the
      "community effect" which requires many competent cells to be present in a group
      to be able to respond to an inductive signal. The RPEt then expands centrifugally
      and underneath the surrounding NR sheet. To determine if the RPEt maintains its
      identity in isolation while displaying the RPE-typical phenotypic plasticity, we
      explanted the islands of RPEt and treated half of them with bFGF. The untreated
      RPEt maintained its closely packed, polygonal pigmented phenotype but the bFGF
      treated RPEt transdifferentiated into a non-pigmented, NR-like phenotype,
      indicating that RPEt encompasses the full differentiation repertoire of native
      RPE.

PMID- 11461000
TI  - Synergistic action of HNF-3 and Brachyury in the notochord differentiation of
      ascidian embryos.
AB  - In vertebrate embryos, the class I subtype forkhead domain gene HNF-3 is
      essential for the formation of the endoderm, notochord and overlying ventral
      neural tube. In ascidian embryos, Brachyury is involved in the formation of the
      notochord. Although the results of previous studies imply a role of HNF-3 in
      notochord differentiation in ascidian embryos, no experiments have been carried
      out to address this issue directly. Therefore the present study examined the
      developmental role of HNF-3 in ascidian notochord differentiation. When embryos
      were injected with a low dose of HNF-3 mRNA, their tails were shortened and when
      embryos were injected with a high dose of HNF-3 mRNA, which was enough to inhibit
      differentiation of epidermis and muscle, no obvious ectopic differentiation of
      endoderm or notochord cells was observed. However, co-injection of HNF-3 mRNA
      along with Brachyury mRNA resulted in ectopic differentiation of notochord cells
      in the animal hemisphere, suggesting that HNF-3 acts synergistically with
      Brachyury in ascidian notochord differentiation. Notochord differentiation of the
      A-line precursor cells depends on inducing signal(s) from endodermal cells, which
      can be mimicked by bFGF treatment. Treatment of notochord precursor cells
      isolated from the 32-cell stage embryoswith bFGF resulted in upregulation of both
      the HNF-3 and Brachyury genes.

PMID- 11461001
TI  - The eyeless mutant gene (e) in the Mexican axolotl (Ambystoma mexicanum) affects
      pax-6 expression and forebrain axonogenesis.
AB  - This study tested the hypothesis that changes in the patterns of pax-6 expression
      disrupt the anatomy and axonogenesis of the diencephalic areas of the eyeless
      axolotl. Proper pax-6 expression is necessary for eye and hypothalamus
      morphogenesis. Since the expression boundaries of pax-6 also provide a permissive
      environment for axonal outgrowth, an extensive study examining the effects of the
      eyeless gene (e) in the Mexican axolotl upon pax-6 expression and forebrain
      axonogenesis was begun. This study used whole embryo in situ hybridization
      techniques to follow pax-6 expression and whole brain immunocytochemistry to
      examine axonogenesis and neural differentiation. These studies demonstrated that
      the mutant gene e in the axolotl alters the response of midanterior neural-plate
      tissue to signals from the prechordal plate. This response was hypothesized to be
      a hyper-response to signals (sonic hedgehog?) that suppressed pax-6 expression
      within the midanterior neural plate and later developmental stages.
      Alternatively, the affected neuroectoderm of the eyeless embryos may lack
      competence to express pax-6. Lowered pax-6 expression inhibited eye and forebrain
      morphogenesis as well as neural axonogenesis and differentiation. Differentiation
      defects were detected as the suppression of midline dopaminergic neurons within
      the suprachiasmatic nucleus of eyeless animals. Thus, lowered pax-6 expression by
      the midanterior neuroectoderm promotes the eyeless condition by inhibiting the
      role of pax-6 in eye formation. This lowered expression also leads to concurrent
      alterations in the hypothalamic terrain which disrupt axonogenesis and ultimately
      promote sterility.

PMID- 11461002
TI  - Mesoderm formation by isolated and cultivated 8-cell stage blastomeres of the
      teleost, Leucopsarion ptersii (shiro-uo).
AB  - Isolation of cleavage-stage blastomeres and the study of their developmental
      potential has been used extensively for analyzing the mechanisms of embryogenesis
      in vertebrates, including amphibians and echinoderms. We devised a method to
      isolate 8-cell stage blastomeres in the teleost, shiro-uo, by utilizing its
      unique cleavage pattern of the horizontal 3rd cleavage plane. Removal of all the
      upper blastomeres at the 8-cell stage allowed almost normal embryogenesis from
      the remaining lower blastomeres and yolk cell mass. Isolated upper or lower
      blastomeres formed vesicles and spherical bodies, which later showed
      morphological changes during cultivation. Mesoderm formation was detected not
      only in the cultivated lower blastomeres or whole blastomeres but also in the
      upper blastomeres isolated from the yolk cell mass at the 8-cell stage, although
      at a lower frequency than the lower blastomeres. These results indicated the
      presence of very early signaling for mesoderm induction, which is independent
      from the currently postulated signals from the yolk syncytial layer at later
      stages. This also indicated non-equivalence or differentiation of the blastomeres
      from the very early cleavage stage in teleost embryos.

PMID- 11461003
TI  - Disto-proximal regional determination and intercalary regeneration in planarians,
      revealed by retinoic acid induced disruption of regeneration.
AB  - The mechanisms that define the body pattern during development and regeneration
      are the object of major concern in developmental biology. To understand the
      process and sequence of antero-posterior pattern formation of planarian body
      regions during regeneration, regenerating organisms were treated with exogenous
      retinoic acid, which affects development and regeneration in other systems, and
      the sequence of regional determination has been monitored by a specific molecular
      marker for the central region, which includes the pharynx. The sequence of gross
      regional specification have never been analysed in planarians using molecular
      regional markers or by direct disruption of the regeneration process. Exogenous
      retinoic acid administration on regenerating planarians disrupts anterior, but
      not posterior regeneration. The period of maximum sensitivity to exogenous
      retinoic acid is one day after amputation, during which time the determination of
      the head has been reported to occur. The data obtained allow us to suggest that
      gross regional specification during planarian regeneration is disto-proximal,
      from the regenerative blastema to the old stump, and thus takes place by
      intercalation of the central region between the anterior and posterior ones.

PMID- 11461004
TI  - Detection of differentially expressed genes in the early developmental stage of
      the mouse mandible.
AB  - We previously examined the development of the mouse mandible, and demonstrated
      that odontogenesis occurs between embryonic day 10.5 (E10.5) and E12. Based on
      the histological findings, we performed cDNA subtraction between the E10.5 and
      E12 mandibles to detect any differentially expressed genes which might be
      involved in the initiation of odontogenesis. By sequencing, homology search and
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), we
      thus found Pgk-1, Ccte, Hsp86, Nucleolin, Hsc73, Frg1, N-ras, Set alpha and Hsj2
      from the E10.5 mandible, and E25, ATPase6, Mum2, Thymosin beta4 and L21 from the
      E12 mandible to be differentially expressed genes. These genes are functionally
      related to protein transport, signal transduction, transcription, translation and
      molecular chaperon activity. In situ hybridization analyses of Set alpha and E25
      showed that Set alpha was detected in the tooth germ at E12 and E14.5, thus
      indicating a close relationship of this gene to odontogenesis. Meanwhile, the in
      situ signal of E25 was found in the muscular layer of the tongue, thus suggesting
      E25 to be related to the differentiation of muscular tissue. In conclusion, we
      found 15 differentially expressed genes in the course of the early developmental
      stage of the mouse mandible using a combination of the cDNA subtraction and semi
      quantitative RT-PCR methods, while in addition, two genes were demonstrated to be
      related to the initiation and the development of both tooth germ and the tongue
      according to the in situ hybridization technique.

PMID- 11461005
TI  - Differential regulation of Dlx gene expression by a BMP morphogenetic gradient.
AB  - Three members of the vertebrate Distal-less gene family, Dlx3, 5 and 6, are
      transcribed in early gastrula embryos of Xenopus laevis. This expression is
      confined to ectoderm and is excluded from the presumptive neural plate region.
      Expression of all three genes is dependent upon BMP signaling, with significant
      differences in how the three genes respond to the BMP antagonist chordin. This
      correlates with the different expression domain boundaries in vivo for Dlx3
      compared to Dlx5 and 6, suggesting that BMP signal attenuation could be the
      primary factor in determining these different patterns in the gastrula ectoderm.

PMID- 11461006
TI  - Redneck, a new mutant of the axolotl (Ambystoma mexicanum) likely affects the
      development of cranial neural crest.
AB  - A novel developmental mutant in the Mexican axolotl is described. Designated
      redneck (rn), the mutant gene is inherited as a simple Mendelian recessive. In
      homozygotes, rn causes massive haemorrhage in the posterior head, rostrocaudal
      compression of the craniovisceral skeleton, abnormal differentiation of vertebral
      cartilage, micrognathia, aglossia, microphthalmia and abnormal hepatic
      development. Affected larvae become evident at the onset of feeding, and
      eventually die of starvation. Based on the tissues affected, we propose that rn
      affects later developmental events in the differentiation and morphogenesis of a
      subset of cranial neural crest cells. Thus, rn may prove a valuable model system
      for examining the role of neural crest cells in the development of cranial and
      endodermal derivatives.

PMID- 11461007
TI  - Selection and amplification of a bone marrow cell population and its induction to
      the chondro-osteogenic lineage by rhOP-1: an in vitro and in vivo study.
AB  - The differentiation and maturation of osteoprogenitor cells into osteoblasts are
      processes which are thought to be modulated by transforming growth factors-beta
      (TGF-beta) as well as by bone morphogenetic proteins (BMPs). Osteogenic protein-1
      (OP-1, also known as BMP-7) is a member of the BMP family, and it is considered
      to have important regulatory roles in skeletal embryogenesis and bone healing.
      Rat bone marrow cells were cultured in vitro in a collagen-gel medium containing
      0.5% fetal bovine serum (FBS) for 10 days in the presence of 40 ng/ml recombinant
      human OP-1 (rhOP-1). Under these conditions, survival of the bone marrow cell
      population was dependent on the presence of rhOP-1. Subsequently, the selected
      cells were cultured-for 6 days in medium containing 40 ng rhOP-1 and 10% FBS.
      During the last 2 days, dexamethasone (10(-8) M) and beta-glycerophosphate (2 mM)
      were added to potentiate osteoinduction. Concomitant with an up-regulation of
      cell proliferation, DNA synthesis levels, colony number and size were determined.
      Chondro-osteogenic differentiation in vitro was evaluated in terms of the
      expression of alkaline phosphatase, the production of osteocalcin and the
      formation of mineralized matrix. After culturing in vitro, cells were placed
      inside diffusion chambers or inactivated demineralized bone matrix (DBM)
      cylinders and implanted subdermically into the backs of old rats for 28 days.
      Biochemical, histological and immunocytochemical analyses provided evidence of
      cartilage and osteoid tissue inside the diffusion chambers, whereas bone was also
      observed inside the DBM implants. In conclusion, this experimental procedure is
      capable of selecting a cell population from bone marrow which, in the presence of
      rhOP-1, achieves skeletogenic potential under in vitro as well as in vivo
      environments.

PMID- 11461008
TI  - Improved performance of protein separation by continuous annular chromatography
      in the size-exclusion mode.
AB  - In size-exclusion chromatography (SEC), proteins and peptides are separated
      according to their molecular size in solution. SEC is especially useful as an
      effective fractionation step to separate a vast amount of impurities from the
      components of interest and/or as final step for the separation of purified
      proteins from their aggregates, in a so-called polishing step. However, the
      throughput in SEC is low compared to other chromatographic processes as good
      resolution can be achieved only with a limited feed volume (i.e., maximal
      approximately 5% of the column volume can be loaded). This limitation opposed
      widespread application of conventional SEC in industry despite its excellent
      separation potential. Therefore a continuous separation process (namely
      preparative continuous annular chromatography) was developed and compared to a
      conventional SEC system both using Superdex 200 prep grade as sorbent. An
      immunoglobulin G sample with a high content of aggregates was chosen as a model
      protein solution. The influence of the feed flow-rate, eluent flow-rate and
      rotation rate on the separation efficiency was investigated. The height
      equivalent to a theoretical plate was lower for preparative continuous annular
      chromatography which could be explained by reduced extra column band broadening.
      The packing quality was proved to be identical for both systems. The productivity
      of conventional batch SEC was lower compared to continuous SEC, consequently
      buffer consumption was higher in batch mode.

PMID- 11461009
TI  - Affinity of the monoclonal antibody M1 directed against the FLAG peptide.
AB  - The FLAG (Sigma, St. Louis, MO, USA) peptide is a frequently used hydrophilic and
      immunogenic fusion tag which was specifically designed to facilitate rapid
      purification by immunoaffinity chromatography. The monoclonal antibody M1
      recognizes the free N-terminus of the peptide tag in a calcium dependent manner.
      Dissociation of the complex can be performed by the addition of chelating agents
      such as EDTA. This effect can be exploited for immunoaffinity purification of
      FLAG-tagged fusion proteins. Kinetic information obtained from monitoring
      interactions in real-time measurement (Biacore 2000) using surface plasmon
      resonance as detection principle did not show any difference for association and
      dissociation rate constants in the presence (k(a) = 3.03 x 10(3) M(-1) k(d) =
      1.25 x 10(-3) s(-1)) and in the absence of Ca2+ (k(a) = 3.59 x 10(3) M(-1) s(-1),
      k(d) = 1.16 x 10(-3) s(-1)). These findings corroborate the reports from Mol.
      Immunol. 33 (1996) 601-608 describing similar binding analyzed by enzyme-linked
      immunosorbent assay experiments. These investigations are in contrast to the
      observations in immunoaffinity chromatography with immobilized anti-FLAG antibody
      M1.

PMID- 11461010
TI  - High-throughput biopolymer desalting by solid-phase extraction prior to mass
      spectrometric analysis.
AB  - In the last 10 years mass spectrometry (MS) has become an important method for
      analysis of peptides, proteins and DNA. It was recently utilized for accurate
      high-throughput protein identification, sequencing and DNA genotyping. The
      presence of non-volatile buffers compromises sensitivity and accuracy of MS
      biopolymer analysis; it is essential to remove sample contaminants prior to
      analysis. We have developed a fast and efficient method for desalting of DNA
      oligonucleotides and peptides using 96-well solid-phase extraction plates packed
      with 5 mg of Waters Oasis HLB sorbent (Waters, Milford, MA, USA). This reversed
      phase sorbent retains the biopolymer analytes, while non-retained inorganic ions
      are washed out with pure deionized water. DNA oligonucleotides or peptides are
      eluted using a small amount (20-100 microl) of acetonitrile-water (70:30, v/v)
      solution. The SPE desalting performance meets the requirements for MS
      applications such as protein digest analysis and DNA genotyping.

PMID- 11461011
TI  - Affinity chromatography of proteins on non-porous copolymerized particles of
      styrene, methyl methacrylate and glycidyl methacrylate.
AB  - Non-porous particles having an average diameter of 2.1 microm were prepared by co
      polymerization of styrene, methyl methacrylate and glycidyl methacrylate, which
      was abbreviated as P(S-MMA-GMA). The particles were mechanically stable due to
      the presence of benzene rings in the backbone of polymer chains, and could
      withstand high pressures when a column packed with these particles was operated
      in the HPLC mode. The polymer particles were advantaged by immobilization of
      ligands via the epoxy groups on the particle surface that were introduced by one
      of the monomers, glycidyl methacrylate. As a model system, Cibacron Blue 3G-A was
      covalently immobilized onto the non-porous copolymer beads. The dye-immobilized
      P(S-MMA-GMA) particles were slurry packed into a 1.0 cm x 0.46 cm I.D. column.
      This affinity column was effective for the separation of turkey egg white
      lysozyme from a protein mixture. The bound lysozyme could be eluted to yield a
      sharp peak by using a phosphate buffer containing 1 M NaCl. For a sample
      containing up to 8 microg of lysozyme, the retained portion of proteins could be
      completely eluted without any slit peak. Due to the use of a shorter column, the
      analysis time was shorter in comparison with other affinity systems reported in
      the literature. The retention time could be reduced significantly by increasing
      the flow-rate, while the capacity factor remained at the same level.

PMID- 11461012
TI  - Polypeptide composition of an adenovirus type 5 used in cancer gene therapy.
AB  - For cancer gene therapy, a recombinant adenovirus serotype 5 named RPR/INGN201
      has been constructed by susbtitution of the E1 region with human tumor suppressor
      gene p53. The protein components of RPR/INGN201 virions were separated by
      reversed-phase HPLC and were individually identified by electrospray time-of
      flight mass spectrometry and N-terminal sequencing, both on intact proteins and
      on their proteolytic fragments after trypsin digestion. Twenty-five peptide
      components of the proteome (including fiber) with greater than 0.25-0.5%
      contribution to the protein content of the virus were identified and
      characterized. Fiber was confirmed to be partially glycosylated (both the non
      glycosylated and the monoglycosylated states were identified), and two proteins
      were isolated and identified as phosphorylation derivatives, namely protein V
      (non-phosphorylated and monophosphorylated) and protein IIIa (mono- and
      diphosphorylated). This new analytical tool proved to be very useful not only for
      refining our current knowledge of the polypeptide repertoire of purified
      infectious virions but also for monitoring and very rapidly identifying
      structural modifications resulting from changes in the manufacturing process. It
      was also used successfully for the characterization of various adenoviral
      constructs.

PMID- 11461013
TI  - Comparison of the properties of phospholipid surfaces formed on HPA and L1
      biosensor chips for the binding of the coagulation factor VIII.
AB  - Binding of a coagulation factor VIII to phosphatidylserine-containing membranes
      is critical for exerting its cofactor activity. The use of surface plasmon
      resonance allows studying factor VIII interaction with immobilized phospholipids.
      In the present study we compared factor VIII-binding properties of phospholipid
      surfaces immobilized on L1 and HPA Biacore chips in the form of a flexible
      bilayer and rigid monolayer, respectively. We demonstrated that immobilized
      phospholipid surfaces with physiological contents of PS and PE formed on L1 but
      not on HPA chip closely mimic intact phospholipid vesicles in their factor VIII
      and thrombin-activated factor VIII (factor VIIIa) binding properties.

PMID- 11461014
TI  - Characterization of clotting factor IX in plasma-derived preparations by
      electrophoretic techniques.
AB  - Clotting factor IX preparations from human plasma (pdFIX) have been characterized
      using electrophoretic methods like sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, isoelectric focusing and two-dimensional polyacrylamide gel
      electrophoresis. Factor IX prior to and after activation with factor XIa was
      separated by one- and two-dimensional polyacrylamide gel electrophoresis and on
      isoelectric focusing gels. The main differences between the band patterns of the
      two pdFIX preparations are due to their purity. Vitronectin was identified by
      immunological techniques as major accompanying plasma protein, separated from
      factor IX and characterized by isoelectric focusing and two-dimensional
      polyacrylamide gel electrophoresis.

PMID- 11461015
TI  - Electrophoretic behavior of peptides in capillary electrophoresis influence of
      ionic strength and pH in aqueous-organic media.
AB  - Through correct pH, pKa and activity coefficients values, a model describing the
      effect of pH on electrophoretic mobility of substances has been applied to a
      series of peptides in water and in acetonitrile-water mixtures. The derived
      equations permit prediction of the optimum pH for the electrophoretic separation
      from only a few experimental values and they also permit determination of pKa
      values of analytes in the aqueous-organic media employed. Furthermore, the
      electrophoretic resolution between pairs of substances can be predicted, in order
      to evaluate electrophoretic separations of the studied peptides.

PMID- 11461016
TI  - Evaluation of peptide electropherograms by multivariate mathematical-statistical
      methods. I. Principal component analysis.
AB  - Depository effects in slowly metabolised proteins, typically glycation or the
      estimation of products arising from the reaction of unsaturated long-chain-fatty
      acid metabolites (possessing aldehydic groups) are very difficult to assess owing
      to their extremely low concentration in the protein matrix. In order to reveal
      such alterations we applied deep enzymatic fragmentation resulting in a set of
      small peptides, which, if modified, are likely to change their electrophoretic
      properties and can be visualised on the resulting profile. Peptide maps of
      collagen (a mixture of collagen types I and III digested by bacterial
      collagenase) were applied as the model protein structure for detecting the
      nonenzymatic posttranslational changes originating during various physiological
      conditions like high fructose diet and hypertriglyceridemic state. Capillary
      electrophoresis in acidic media (sodium phosphate buffer, pH 2.5) was used as the
      separation method capable of (partial) separation of over 60 peptide peaks. Two
      to 13 changes were revealed in the profiles obtained reflecting the physiological
      conditions of the animals tested. Combination of peptide profiling with
      subsequent t-test evaluation of individual peak areas and principal component
      analysis based on cumulative peak areas of individual sections of the
      electropherograms allowed to determine in which section (part) of the
      electropherogram the physiological state indicating changes occurred.
      Simultaneously it was possible to reveal the qualitative differences between the
      four physiological regimes investigated (i.e., which regime affects the collagen
      molecules most and which affects them least). The approach can be used as
      guidance for targeted preseparation of the very complex peptide mixture.

PMID- 11461017
TI  - Oscillatory electroosmosis-enhanced intra/inter-particle liquid transport and its
      primary applications in the preparative electrochromatography of proteins.
AB  - The concept of generating an oscillatory electroosmotic flux inside the porous
      particle to enhance the intra-particle mass transport was presented and a new
      kind of electrochromatography carried out in a five-compartment electrolyzer were
      developed. The adsorbent was packed in the central compartment, while the
      neighboring compartments were used as the elution compartments and the electrode
      compartments, respectively. Chromatographic separations of human serum albumin on
      Blue Sepharose Fast Flow, bovine serum albumin (BSA) on DEAE-Sepharose Fast Flow,
      and BSA on hydroxyapatite were carried out, respectively. The adsorption
      isotherms were shown to be independent of electric field, while the increase in
      the electric field strength resulted in a linear increase in the magnitude of
      electroosmotic flux and the improvement of the breakthrough behavior in all
      cases. The experiment results have demonstrated the effectiveness of the
      oscillatory electroosmosis in enhancing intra- and inter-particle mass transport
      and its high potential to large-scale chromatography.

PMID- 11461018
TI  - Open-tubular electrochromatography of organic phosphates on a sapphyrin-modified
      capillary.
AB  - Sapphyrin coating of the inner wall of the capillary results in a distinct
      interaction of the phosphate residue-possessing compounds as proven by a seven
      membered model mixture of nucleoside mono- and diphosphates and ATP. Modification
      of the inner surface of the capillary not only alters the endoosmotic flow (as
      would have been expected) but brings about an electrochromatographic effect based
      on the interaction of tested phosphate moiety-bearing solutes with the
      immobilized sapphyrin layer. Elution of the sample can be achieved by using
      either 25 mM borate-acetate buffer in which monophosphates are not only separated
      from each other, but also selectively separated from di- and triphosphates (ATP).
      With the other two buffer systems tested, i.e. borate-phosphate and Tris-HCl,
      better selectivity (though smaller interaction with the capillary coating) was
      observed. The coating is relatively stable (can be used for 20 subsequent runs at
      least), simple to materialize, and in spite of a strong UV absorbancy of
      sapphyrin at the wavelength used (254 nm), decreases the limit of detection by no
      more than one order of magnitude as compared to the untreated capillary.
      Resolution factors (calculated to the preceding peak) are in most cases better in
      the electrochromatographic separation mode as compared to the separation in the
      untreated capillary, which reflects both the decrease in the electroosmotic flow
      and the interaction with the capillary wall coating.

PMID- 11461019
TI  - A job well done!

PMID- 11461020
TI  - Using evidence-based practice to improve intrapartum care.
AB  - The Cochrane Data Base (www.cochranelibrary. com/clibhome/clib.htm, retrieved
      February 23, 2001), a comprehensive international review of current medical and
      obstetric practices, demonstrates that birth outcomes improve with one-to-one
      labor support but not necessarily with continuous fetal monitoring. Because of a
      cultural bias toward technology, however, few extrinsic rewards exist for nurses
      who provide individualized labor support. Clinical scholarship in the obstetric
      setting is one way to begin changing ritualized practices, incorporating evidence
      based practice, and improving nursing care.

PMID- 11461021
TI  - Fetal nuchal translucency: a prenatal screening tool.
AB  - During fetal nuchal translucency screening, ultrasonography is used to assess for
      a fluid collection at the nape of the fetal neck. An abnormal fluid collection
      may be related to genetic disorders and/or physical anomalies. This screening is
      most accurate when performed between 10 and 14 weeks gestation. Analyzing
      maternal serum beta-hCG and pregnancy-associated plasma protein A levels
      increases the accuracy of 1st trimester screening. Nurse practitioners, midwives,
      and physicians can be certified in performing fetal nuchal translucency
      screening.

PMID- 11461022
TI  - Expert in fertility appreciation: the Creighton Model practitioner.
AB  - The Creighton Model system of natural family planning (NFP) is useful in
      achieving pregnancy, avoiding pregnancy, and detecting some gynecologic
      disorders. NFP practitioners support the client in using NFP. Because the
      effectiveness of NFP is related to the teaching process and to teacher expertise,
      clients choosing NFP may be best served by referral to a certified NFP
      practitioner for instruction.

PMID- 11461023
TI  - Breastfeeding trends at a Community Breastfeeding Center: an evaluative survey.
AB  - OBJECTIVE: To evaluate the Community Breastfeeding Center's (CBC) impact on
      clients' breastfeeding experiences. DESIGN: Retrospective survey; participants
      were mailed a questionnaire. SETTING: A hospital-based drop-in center operated
      jointly by the Wellington-Dufferin-Guelph Health Unit and Headwaters Health Care
      Center and offering professional breastfeeding support and peer interaction.
      PARTICIPANTS: The 164 mothers of singleton births, both inpatients and community
      clients, who attended the CBC during a 10-month period in 1996-1997 and completed
      a survey. MAIN OUTCOME MEASURES: A mailed survey with forced-choice and open
      ended questions. RESULTS: Of the respondents, 90.9% rated their overall CBC
      experience as excellent or good. Seventy-three percent of respondents breastfed
      for 4 months or longer. Primiparae and mothers of preterm infants tended to visit
      the CBC more frequently, while achieving duration rates similar to other
      subgroups. Returning to work was the reason most frequently cited for stopping
      breastfeeding (35%). CONCLUSION: The CBC is an effective community support
      strategy to lengthen breastfeeding duration and enhance clients' satisfaction
      with their breastfeeding experience.

PMID- 11461024
TI  - The little things: perceptions of breastfeeding support.
AB  - OBJECTIVE: To describe how maternal-child staff nurses support breastfeeding
      mothers during the postpartum hospital stay and how these mothers perceive the
      support received from the nurses. DESIGN: Ethnographic. SETTING: Data were
      collected at a community hospital in southeastern Florida. PARTICIPANTS:
      Unstructured interviews were conducted with seven maternal-child nurses caring
      for breastfeeding mothers. The investigator observed 12 nurses' interactions with
      breastfeeding mothers and newborns. Eight breastfeeding mothers were interviewed,
      using a semistructured guide, in the hospital before discharge and at 2 and 6
      weeks postpartum. RESULTS: Nurses supported breastfeeding mothers by providing
      information and interpersonal support. Breastfeeding mothers expected the nurses
      to support their feeding efforts by providing information, encouragement, and
      interpersonal support. CONCLUSION: Health care providers can help breastfeeding
      mothers, but the support offered must be the kind that mothers want.

PMID- 11461025
TI  - The relationship between social support and adolescent mothers' interactions with
      their infants: a meta-analysis.
AB  - OBJECTIVE: The purpose of this meta-analysis was to statistically summarize the
      results of independent quantitative studies regarding the relationship between
      social support and adolescent mothers' interactions with their infants. DATA
      SOURCES: The following sources were selected from 1980 to 1999: citations from
      bibliographies of previously located articles, dissertations abstracts, the
      Social Sciences Citation Indexes, and researchers at a regional conference;
      online sources used were CINHAL, MEDLINE, ERIC, Psych Lit, and Social Work
      Abstracts. STUDY SELECTION: Of a potential sample of 31 studies, 14 were excluded
      because they did not meet the sampling criteria, and 4 were deleted as outliers.
      The final sample consisted of 13 studies. DATA EXTRACTION: Each study was coded
      for methodologic and substantive variables, including quality indicators. DATA
      SYNTHESIS: Most of the studies were cross sectional in design and used a variety
      of measures. Together, the studies included a sample of 823 mothers. CONCLUSIONS:
      A medium effect size and a significant relationship between social support of
      adolescent mothers and their interactions with their infants were established. No
      difference was found in the relationship when support was provided by the family
      or through a network.

PMID- 11461026
TI  - Dimensions of sexuality in the perimenopausal transition: a model for practice.
AB  - A biopsychosocial-cultural model of the sexuality of women during the
      perimenopausal transition includes dimensions related to physiology, psychosocial
      issues, and culture. It is an amalgam of biomedical and psychosocial models, yet
      has the added focus on culture. This holistic approach to sexual health is
      recommended by researchers and clinicians engaged in the study of midlife women.
      Clinicians can use this model to guide assessment and interventions, examining
      all of the dimensions of sexuality during the perimenopausal transition.

PMID- 11461027
TI  - Sexual protective strategies of late adolescent females: more than just condoms.
AB  - OBJECTIVE: To identify the sexual protective strategies of late adolescent
      heterosexual women. DESIGN: Open-ended questioning regarding sexual protective
      strategies was included in a larger cross-sectional survey on sexual risk.
      Participants' responses were recorded verbatim and analyzed using content
      analysis. PARTICIPANTS: 234 African American, Hispanic/ Latina, and non-Hispanic
      white 19- to 21-year-old females were recruited from the driver's license records
      of a mid-Atlantic state. MAIN OUTCOME MEASURES: Participants responded to the
      open-ended question, "How or what do you do to reduce your risk for sexually
      transmitted diseases and HIV?" RESULTS: Seven primary sexual protective
      strategies were identified from participants' responses: using condoms,
      abstaining or postponing sexual intercourse, getting tested for human
      immunodeficiency virus (HIV) and sexually transmitted diseases (STDs), selecting
      safe partners, negotiating condom use, talking about sexual risk histories, and
      limiting the number of sexual partners. CONCLUSIONS: Some of the sexual
      protective strategies identified by study participants were less than effective
      and left young women vulnerable to infection with HIV and STDs. In addition, the
      use of these alternative strategies may leave young women feeling less at risk
      and thus less likely to use other more effective strategies such as condoms. The
      implications for nursing practice and the assessment of the sexual protective
      strategies of young heterosexual women are discussed.

PMID- 11461028
TI  - Sexuality and safer sex: the issues for lesbians and bisexual women.
AB  - Nursing interventions to help women reduce their risk of contracting HIV must be
      designed from an in-depth understanding of the complex sociocultural patterns of
      sexuality in particular communities and among specific subgroups. OBJECTIVE: In
      this data collection phase of a community-based HIV prevention project, the
      objective was to understand HIV risk-taking and HIV risk-reduction activities of
      lesbians and bisexual women. DESIGN: Qualitative field study. SETTING: Data were
      collected in women's bars and dance clubs and at selected lesbian/bisexual
      community events in San Francisco. PARTICIPANTS: Interviews were conducted with
      1,189 racially diverse, socially and sexually active lesbians and bisexual women.
      RESULTS: Inductive content analysis produced two themes: realities of sexual
      behavior and sexual expressions and their meanings. Realities of sexual behavior
      included an assumption that women who have sex with other women cannot get HIV, a
      lack of familiarity with HIV prevention strategies, inconsistent practice of
      safer sex with men and/or women, and the negative effect of alcohol or drug use
      on safer sex efforts. Sexual expressions and their meaning included trust in
      monogamy, a sense that safer sex practices detracted from intimacy and eroticism,
      the difficulty of negotiating sexual behaviors with men or women, and dealing
      with partner resistance to safer sex practices. CONCLUSIONS: Specific
      recommendations for practice are the need for nurses to understand the range and
      diversity of women's sexual behaviors, to develop skills in conducting inclusive
      sexual histories, and to develop a comprehensive approach to sexual health.

PMID- 11461029
TI  - Antigenic variation in trypanosomes: enhanced phenotypic variation in a
      eukaryotic parasite.
AB  - African trypanosomes are unicellular, eukaryotic parasites that live
      extracellularly in a wide range of mammals, including humans. They have a surface
      coat, composed of variant surface glycoprotein (VSG), which probably is essential
      and acts as a defence against general innate immunity and against acquired
      immunity directed at invariant surface antigens. In effect, the VSG is the only
      antigen that the host can target, and each trypanosome expresses only one VSG. To
      counter specific antibodies against the VSG, trypanosomes periodically undergo
      antigenic variation, the change to expression of another VSG. Antigenic variation
      belongs to the general survival strategy of enhanced phenotypic variation, where
      a subset of 'contingency' genes of viruses, bacteria and parasites hypermutate,
      allowing rapid adaptation to hostile or changing environments. A fundamental
      feature of antigenic variation is its link with the population dynamics of
      trypanosomes within the single host. Antigenic variants appear hierarchically
      within the mammalian host, with a mixture of order and randomness. The underlying
      mechanisms of this are not understood, although differential VSG gene activation
      may play a prominent part. Trypanosome antigenic variation has evolved a second
      arm in which the infective metacyclic population in the tsetse fly expresses a
      defined mixture of VSGs, although again each trypanosome expresses a single VSG.
      Differential VSG expression enhances transmission to new hosts, in the case of
      bloodstream trypanosomes by prolonging infection, and in the metacyclic
      population by generating diversity that may counter existing partial immunity in
      reservoir hosts. Antigenic variation employs a huge repertoire of VSG genes. Only
      one is expressed at a time in bloodstream trypanosomes, as a result of
      transcription being restricted to a set of about 20 bloodstream expression sites
      (BESs), which are at chromosome telomeres. Only one BES is active at a time,
      probably through transcriptional elongation being inhibited in the silent BESs.
      Although transcriptional switching between BESs can effect a VSG switch, the most
      prolific switch route involves homologous recombination of deoxyribonucleic acid,
      usually by the copying of a silent gene into a BES. Hierarchical expression of
      VSGs may be dictated in part by the different types of locus occupied by VSG
      genes. The VSG genes expressed in the metacyclic population also occupy telomeric
      sites, which appear to be derived from BESs but have a simpler structure. Their
      differential expression is achieved by random transcriptional activation; the
      detailed story requires direct study of the metacyclic stage itself. Available
      evidence suggests that the VSG originated as a surface receptor, and it can be
      proposed that a number of selective events have contributed to the evolution of
      the complex, multisystem phenomenon that antigenic variation has become.

PMID- 11461030
TI  - Apoptosis and parasitism: from the parasite to the host immune response.
AB  - Apoptosis, a form of programmed cell death (PCD), plays a central role in normal
      tissue development as well as in the pathogenesis of different diseases. PCD is
      responsible for the non-inflammatory physiological elimination of potentially
      harmful or unnecessary cells during embryogenesis, and for the proper functioning
      of continuous cell renewal systems in adult organisms. Maturation of the immune
      system and the specific immune response are examples of situations where PCD
      plays important roles. This review discusses the importance of apoptosis in two
      fundamental elements of a host-parasite interaction: the parasite (Section 1),
      and the host's immune response (Section 2). Section 1 discusses questions raised
      by the description of apoptosis in unicellular eukaryotes, such as the
      evolutionary origin of the molecular components of PCD, its role in the emergence
      and maintenance of parasitism, and the constraints of a multicellular
      organization for the proper operation of a cell death programme. The proposal is
      that PCD can occur in any situation where living cells display features of an
      organized network which operates through interactions within themselves and/or
      with elements of their environment. The possibility is also discussed that
      evolutionary relics of a complete cell death system may operate in unicellular
      parasites with functions other than inducing cell death. Section 2 reviews data
      on the mechanisms of host-cell PCD and the consequences of this phenomenon in
      host defence and pathogenesis. Infectious agents, from viruses to parasites, can
      either delay or induce apoptosis of different types of host cells. Apoptosis
      following lymphocyte polyclonal activation and stimulation of peripheral T
      lymphocytes, as a result of the engagement of specific counter-receptor systems,
      is of special interest for defining host immunocompetence and mechanisms of
      immunopathology.

PMID- 11461031
TI  - Biology of echinostomes except Echinostoma.
AB  - This review examines the significant literature on the biology of echinostomes,
      except Echinostoma, for the following species rich genera: Echinoparyphium,
      Echinochasmus, Himasthla, and Hypoderaeum. Coverage of these genera includes
      descriptive studies, life cycle studies, experimental and manipulative studies,
      and biochemical and molecular studies. Coverage of other echinostome genera,
      i.e., Petasiger, Euparyphium, Stephanoprora, Isthmiophora, Acanthoparyphium, and
      Patagifer was mainly concerned with descriptive and life cycle studies. Some
      groups that are considered echinostome-like were covered because species in these
      genera have medical, economic, or biological significance (particularly
      Parorchis, Philophthalmus, and Ribeiroia). A dominant theme of the review is the
      availability of key species of echinostomes for use in biological research;
      coverage also includes methods for obtaining and maintaining these organisms in
      the laboratory. Some species with significant medical, veterinary, and biological
      importance that have been covered extensively include the Echinoparyphium
      recurvatum species complex, Echinochasmus liliputanus, Himasthla quissetensis,
      Himasthla rhigadana, and Hypoderaeum conoideum.

PMID- 11461032
TI  - The epidemiology and control of human African trypanosomiasis.
AB  - Human African trypanosomiasis is caused by Trypanosoma brucei gambiense in West
      and Central Africa, and by Trypanosoma brucei rhodesiense in East and southern
      Africa. In recent years there has been a dramatic resurgence of Gambian
      trypanosomiasis in Central Africa, especially in the Democratic Republic of
      Congo, Angola and Sudan. The disease is quiescent in most of West Africa, as is
      Rhodesian trypanosomiasis the other side of the continent. The epidemiology of
      Gambian trypanosomiasis is reviewed in detail. The long duration of infection in
      human hosts with cycles of intermittent parasitaemia, the vectors' feeding habits
      and the intensity of human-fly contact are the major determinants of the dynamics
      of transmission of this parasite. The development of immunity may lead to a
      reduction in the fraction of the population that is susceptible to infection and
      the burning out of epidemics after 20 to 30 years. So far, the acquired immune
      deficiency syndrome pandemic has had no impact on the epidemiology of Gambian
      trypanosomiasis. A brief review of the epidemiology of Rhodesian trypanosomiasis
      highlights the differences from Gambian trypanosomiasis that, to some extent,
      explain its lower propensity to cause epidemics: it is a more aggressive disease
      that rapidly kills its human host, and its transmission involves mostly domestic
      and game animals, humans being in most circumstances an accidental host. The
      various methods and strategies for the surveillance and control of both diseases
      are reviewed.

PMID- 11461033
TI  - A field evaluation of monitor placement effects in VDT users.
AB  - Appropriate visual display terminal (VDT) location is a subject of ongoing
      debate. Generally, visual strain is associated with higher placement, and
      musculoskeletal strain is associated with lower placement. Seeking resolution of
      the debate, this paper provides a comparison of results from previous lab-based
      monitor placement studies to recommendations and outcomes from viewing preference
      and neutral posture studies. The paper then presents results from a field study
      that addressed two outstanding issues: Does monitor placement in a workplace
      elicit postures and discomfort responses similar to those seen in laboratory
      settings? Results showed placements in the workplace elicited postures similar to
      those in lab studies. Additionally, preferred VDT location generally corresponded
      to the location in which less neck discomfort was reported, though that trend
      requires further investigation. Overall, there seems to be consistent evidence to
      support mid-level or somewhat higher placement, as a rule-of-thumb, considering
      preferred gaze angle and musculoskeletal concerns. However, optimal placement may
      be lower for some individuals or tasks.

PMID- 11461034
TI  - How safe is adventure tourism in New Zealand? An exploratory analysis.
AB  - The paper reports findings from a multidisciplinary programme of research, the
      major aims of which were to determine the nature and extent of the New Zealand
      adventure tourism injury problem. Analysis of hospital discharge and mortality
      data for a 15-year period identified adventure tourism-related activities as
      contributing to approximately 20% of overseas visitor injuries, and 22% of
      fatalities. Activities that commonly involve independent-unguided adventure
      tourism, notably mountaineering, skiing and tramping, contributed most to injury
      and fatality incidence. Horse riding and cycling activities were identified from
      hospital discharge data and adventure tourism operators' reported client injury
      incidence, as the commercial adventure tourism activities most frequently
      involved in client injuries. Falls were the most common injury events, and a
      range of client, equipment, environmental and organisational risk factors were
      identified. Possible interventions to reduce injury risk among overseas and
      domestic adventure tourists are discussed.

PMID- 11461035
TI  - Anthropometric study of Mexican primary school children.
AB  - This paper presents the results of an anthropometric survey conducted on male and
      female Mexican primary school children age 6-11 years in the metropolitan area of
      the city of Guadalajara. A set of 50 body dimensions was taken based on
      international standards. The sample consisted of 4758 children (boys and girls).
      The anthropometric measurements were compared to those of American, Cuban and
      Mexican children. The results indicate that the body dimensions of Mexican
      children from this study are different from those of American, Cuban, and other
      Mexican children, probably due to ethnic differences and the time lapse between
      the different studies. It is considered that the 50 parameters are necessary for
      the design of school furniture, fittings and equipment in order to minimize
      musculoskeletal, visual, and circulatory problems resulting from using those
      badly designed elements.

PMID- 11461036
TI  - Buttock and back pressure distribution tests on seats of mobile agricultural
      machinery.
AB  - Multidisciplinary effort is usually required in the evaluation of comfort
      problems in the working environment of mobile agricultural machinery workers.
      Comfort can be partly assessed from the study of the pressure distribution of the
      human-seat interface. Four combine foam seats and a new air-based seat were
      compared with regards to static buttocks and back support pressures. Within and
      between subject variability and the issue of measurement repeatability were
      addressed. Significant differences were found in the maximum pressure profiles of
      the four seating systems with seats 2 and 3 performing better than seat I (seat 4
      showed no significant difference when compared to the other seats). There is an
      almost linear relationship between mean pressure and body mass index. In all
      cases the air seating system performed better with regards to the static pressure
      gradients.

PMID- 11461037
TI  - LUBA: an assessment technique for postural loading on the upper body based on
      joint motion discomfort and maximum holding time.
AB  - This paper presents a technique for postural loading on the upper body assessment
      (LUBA). The proposed method is based on the new experimental data for composite
      index of perceived discomfort (ratio values) for a set of joint motions,
      including the hand, arm, neck and back, and the corresponding maximum holding
      times in static postures. Twenty male subjects participated in the experiment
      designed to measure perceived joint discomforts. The free modulus technique of
      the magnitude estimation method was employed to obtain subjects' discomforts for
      varying joint motions. The developed postural classification scheme was based on
      the angular deviation levels from the neutral position for each joint motion.
      These were divided into groups with the same degree of discomforts based on the
      statistical analysis. Each group was assigned a numerical discomfort score
      relative to the perceived discomfort value of elbow flexion, which exhibited the
      lowest level among all joint motions investigated in this study, and, therefore,
      was set as a reference point. The criteria for evaluating stresses of working
      postures were proposed based on the four distinct action categories, in order to
      enable practitioners to apply appropriate corrective actions. The proposed scheme
      can be used for evaluating and redesigning static working postures in industry.

PMID- 11461038
TI  - The influence of supporting the Oxylog instrument on estimated maximal aerobic
      capacity during a step test and heart rate in a lifting test.
AB  - This study investigated the influence of wearing, an Oxylog mask and heart rate
      monitor while the Oxylog instrument was supported in a stand versus that of
      wearing the Oxylog mask, heart rate monitor, and the Oxylog instrument, on oxygen
      consumption (VO2) and heart rate response during a graduated submaximal step test
      protocol. Also, the predicted maximal aerobic capacities ( VO2max) produced by
      the two graduated step tests were compared. In addition, differences in the
      working heart rates in a submaximal lifting test were analyzed in two lifting
      tests, one with the participant wearing the Oxylog mask, heart rate monitor, and
      Oxylog instrument and the other required the participant to only wear a heart
      monitor. Seventeen experienced male manual materials handlers participated in the
      study, and each treatment was seen by each participant in a randomized Latin
      Square design. Results from the two investigations indicate that there was no
      significant difference in the estimated maximal oxygen consumption (p = 0.1384)
      and no significant difference in the heart rate between the two lift tests. The
      analysis did show that the 4th stage (participants reaching their physiological
      limits) of the step tests indicated a statistically significant difference (p =
      0.0259 for oxygen consumption, and p = 0.0465 for heart rate).

PMID- 11461039
TI  - Shoe design for prevention of injuries in sport climbing.
AB  - Foot injuries and deformations are more frequent at higher levels of sport
      climbing. These are accepted as unavoidable because it is assumed that, for
      optimal performance, a prerequisite is the wearing of a shoe, which is too tight
      and has an unnatural shape. Based on a biomechanical analysis, we came up with a
      different approach to shoe design. By using regional thinning of the sole, easy
      flexion and extension of the toes is made possible. The form of the shoe conforms
      to the natural form of the foot, the shoe closure provides a close fit for feet
      with width differences of up to 20 mm and a shoe-sizing system was developed.
      After testing prototypes, we conclude that the new shoe design can contribute to
      the prevention of foot injuries and deformations in sport climbing.

PMID- 11461040
TI  - Heart rate strain in cable hauler choker setters in New Zealand logging
      operations.
AB  - This study examined the physical strain experienced by cable hauler choker
      setters, and the applicability of heart rate indices for measuring physical
      strain in commercial forest harvesting operations in New Zealand. The heart rate
      of four choker setters were recorded continuously throughout the working day and
      applied to heart rate indices. Based on the relative heart rate at work (%HRR),
      ratio of working heart rate to resting heart rate and 50% level indices, the mean
      working heart rate (HRw) of 106 bt. min(-1) +/- 6.9 (mean +/- SD) placed choker
      setting in the moderate workload category. The specific tasks of line shifts
      (120.3 +/- 4.8 bt. min(-1)), hooking up drags (118.8 +/- 6.6 bt. min(-1)) and
      uphill travel (126.1 +/- 12.9 bt. min(-1)), imposed the most severe workloads on
      the choker setters. This research also demonstrated that heart rate indices could
      be used as an effective means of determining the physiological strain of subjects
      working in New Zealand's commercial forest harvesting operations.

PMID- 11461041
TI  - An evaluation of physiological demands and comfort between the use of
      conventional and lightweight self-contained breathing apparatus.
AB  - The additional physiological strain associated with the use of self-contained
      breathing apparatus (SCBA) is mostly linked to the additional weight. Lightweight
      and conventional SCBA were assessed in a submaximal step test performed in full
      firekit (total weights 15 and 27 kg, respectively). Factors assessed were:
      comparative energy expenditure of the two sets, relationship between comparative
      energy expenditure and aerobic fitness and subjective discomfort. Measured
      variables were: oxygen consumption, heart rate, estimated VO2max and subjective
      discomfort (body part discomfort scale). The lightweight SCBA displayed a
      significant oxygen consumption benefit, which was independent of dynamic workrate
      and valued at 0.2561 min(-1). Mean heart rate responses were significantly lower
      with the light set. No relationship was found between comparative energy
      expenditure and aerobic fitness. The light set was rated as significantly more
      comfortable than the heavy. Further research is required to assess the extent of
      the energy consumption benefit in realistic fire suppression protocols and the
      contribution of ergonomic factors to the energy and comfort benefits.

PMID- 11461042
TI  - The impact of draught related to air velocity, air temperature and workload.
AB  - This experimental study was designed to test the hypotheses that the effects of
      draught increase with higher air velocity, with lower air temperature, and with
      lower workload. Thirty healthy young males were exposed to horizontal draught
      during 55 min while they operated an arm ergometer in a standing posture. Air
      velocity, air temperature, and workload were varied in 3 steps each, between 11
      and 23 degrees C, 0.1 and 0.3 m/s, and 104 to 156 W/m2, respectively. The 27
      combinations were distributed over subjects in a fractional factorial 3(3)
      design. The participants were clothed for thermal neutrality. Workload was
      measured at the end of the sessions by respirometry. Draught-induced annoyance
      was determined every 5 min, separately for 10 body sites. Corresponding skin
      temperature was also recorded. The hypotheses were verified for the influence of
      air velocity and air temperature. Regarding workload, local heat production is
      probably decisive, meaning that draft-induced local annoyance is inversely
      related to workload in active but independent from workload in non-active body
      areas. To improve the situation for the workers concerned it is suggested to
      apply protective gloves that cover an as great area of the forearms as possible
      and to limit airflows to mean velocities of less than 0.2 m/s (with turbulence
      intensities of 50%).

PMID- 11461043
TI  - Antibacterial activity of bactenecin 5 fragments and their interaction with
      phospholipid membranes.
AB  - Bactenecin 5 (Bac 5) is an antibacterial 43mer peptide isolated from bovine
      neutrophils. It consists of an Arg-rich N-terminal region and successive repeats
      of Arg-Pro-Pro-Ile (or Phe). We synthesized Bac 5(1-23) and several related
      peptides to clarify the roles these regions play in antibacterial activity. An
      assay of antibacterial activity revealed that such activity requires the presence
      of Arg residues at or near the N-terminus, as well as a chain length exceeding 15
      residues. None of the peptides exhibited haemolytic activity. Polyproline II-like
      CD curves were observed for most of the peptides. Measurements of the membrane
      perturbation and fusion indicated that the perturbation and fusogenic activities
      of the peptides were, generally, parallel to their antibacterial activities.
      Amino acid substitution in the repeating region had some effect on antibacterial
      activity.

PMID- 11461044
TI  - Location of disulfide bonds in mature alpha-L-fucosidase from pea.
AB  - Fuc-9 is the mature form of a vacuolar alpha-L-fucosidase enzyme which seems to
      play an important role in plant growth regulation. Fuc-9 is a 202-residue protein
      containing five Cys residues located at positions 64, 109, 127, 162 and 169. In
      this study, the disulfide structure of Fuc-9 was determined by MALDI-TOF mass
      spectrometry (MS), with minimal clean-up of the samples and at a nanomolar scale.
      Two strategies, based on a specific chemical cleavage (with 2-nitro-5
      thiocyanobenzoic acid and alkaline conditions) at the Cys residues and
      modification of Cys residues by acrylamide/deuterium labeled acrylamide
      alkylation, were used. Using these methods, the disulfide pairings Cys64-Cys109
      and Cys162-Cys169 could be established. The advantages and limitations of our
      experimental approach are discussed.

PMID- 11461045
TI  - Configuration and racemization determination of cysteine residues in peptides by
      chiral derivatization and HPLC: application to oxytocin peptides.
AB  - An improved RP-HPLC method was developed for the determination of the
      configuration and stereochemical purity of cysteine residues in peptides. The
      method consists of oxidation of cysteine and cystine residues to cysteic acid,
      followed by hydrolysis and pre-column chiral derivatization with Val-Marfey's
      reagent.

PMID- 11461046
TI  - Conformation of the tripeptide Cbz-Pro-Leu-Trp-OBzl(CF3)2 deduced from two
      dimensional 1H-NMR and conformational energy calculations is related to its
      affinity for NK1-receptor.
AB  - Chemical modifications of dual NK1/NK2 ligand Cbz-Gly-Leu-Trp-OBzl(CF3)2 (1)
      enabled us to create a high NK1 selective ligand Cbz-Pro-Leu-Trp-OBzl(CF3)2 (2).
      A determination of the conformational behavior of tripeptide 2 in solution is
      described. The 1D and 2D 1H-NMR techniques (COSY and ROESY) were used to assign
      resonances. Observed interproton distance restraints were considered to
      characterize conformational behavior. Spectral data indicate that tripeptide 2
      presents a rigidified structure in DMSO stabilized by H-bond in two gamma-turns.
      Agreement with experimental data was obtained by averaging the 1H-NMR parameters
      over several combinations of low-energy conformations.

PMID- 11461047
TI  - Haptenization of ovalbumin with the skin sensitizer methyl octanesulfonate:
      characterization of the methylated OVA323-339 T-cell epitope at His331.
AB  - Our interest is focused on the induction of allergic contact dermatitis (ACD) by
      the strong skin sensitizer, methyl octanesulfonate, which is a potent methyl
      transfer agent, especially to histidine and methionine residues. We are
      particularly interested to study the effect of methylation on the presentation
      and recognition of the ovalbumin (OVA) T-cell epitope, OVA323-339, by the T-cell
      receptor (TCR). Here we report the synthesis of the modified monomer N-alpha-Fmoc
      N-tau-methyl-L-histidine and its incorporation by solid phase synthesis into the
      three possible methylated analogues of OVA323-339, that were needed as references
      for the subsequent studies. Native OVA was haptenized by methyl octanesulfonate.
      Using classical protein chemistry techniques (trypsin digestion, gel permeation,
      HPLC, MS and Edman sequencing) we were able to show that OVA323-339 was
      selectively methylated at His331. Circular dichroism (CD) studies showed that the
      methylation has no influence on the secondary structure of the peptide.

PMID- 11461048
TI  - Synthesis of linear and comb-like peptide constructs containing up to four copies
      of a T cell epitope and their capacity to stimulate T cells.
AB  - Polypeptide constructs containing up to four copies of the T cell epitope 306-318
      of influenza virus haemagglutinin have been synthesized on solid phase. Between
      the copies, a non-natural PEG-based spacer amino acid has been introduced. The
      oligomeric epitopes were analysed by RP-HPLC and ES-MS. The arrangement of the
      epitopes within the peptide constructs was either linear or comb-like. The
      proliferative response in a T helper cell assay induced by these oligomerized
      epitopes has been tested, showing that the linearly arranged epitopes are more
      effective than the comb-like oligomers.

PMID- 11461049
TI  - Writing for the Journal of Sports Sciences.

PMID- 11461050
TI  - Exploring self-talk and affective states in sport.
AB  - In this study, we examined (1) the relationship between self-talk and affect and
      (2) the nature of motivating self-talk. Ninety high-school athletes completed the
      Affect Grid and the Self-Talk Grid before practice and competition. Significant
      positive second-order partial correlations of low to moderate strength offered
      support for a relationship between self-talk and affect. In addition, significant
      positive second-order partial correlations of moderate strength were found for a
      relationship between negative-positive self-talk and demotivating-motivating self
      talk. An examination of scatter plots indicated that some athletes rated their
      self-talk as negative as well as being motivational. These findings lend support
      to the suggestion that negative self-talk may motivate some athletes.

PMID- 11461051
TI  - Scaling laws and forecasting in athletic world records.
AB  - In this study, we analysed running world records and found that the mean speed of
      the race, mu, as a function of the record time, tau, can be described
      asymptotically by two well-defined scaling laws of the form mu approximately tau(
      beta). There is a break in the scaling laws (approximately 1000 m) between the
      shorter and the longer races at a characteristic time of around 150-170 s, after
      which a new scaling regime emerges. This is the first occasion that this
      characteristic time has been clearly found in physical terms; we interpreted it
      as the transition time between the anaerobic and the aerobic energy expenditure
      of athletes. This phenomenon is independent of the athletes' sex and is also
      found in swimming races with similar values of the characteristic time. We also
      investigated the forecasting of world records using historical data. Using an
      approach based on the identification of non-Poissonian events for a sequence of
      temporal point processes, we found that the sequence of improvements in all
      athletic records from 1900 to the present day cannot be considered as a sequence
      of completely random events.

PMID- 11461052
TI  - Human perceptions of sports equipment under playing conditions.
AB  - Assessment of the 'performance' of sports equipment is generally derived from
      physical and technical parameters, such as power, speed, distance and accuracy.
      However, from a psychological perspective, players need to feel comfortable with
      their equipment and confident in its properties. These factors can only be
      measured through the subjective assessment of individual perceptions. Focusing on
      a group of elite golfers, this study presents a formalized approach for eliciting
      and structuring players' descriptions of their perception of sports equipment.
      Qualitative methods of inquiry were used to generate perceptions from a group of
      professional golfers (n = 15) during play testing. The equipment characteristics
      of significance to the golfers emerged from an inductive analysis of their
      responses. However, although this method of representation of the results helped
      to identify the key components or dimensions of a player's subjective perception,
      it was unable to determine potential relationships between the dimensions. With
      this in mind, a new technique, called 'structured relationship modelling', was
      developed. Ten general dimensions emerged from the analysis, of which three are
      presented here together with a section of the relationship model. The results
      demonstrate the effectiveness of qualitative techniques for eliciting human
      perceptions and of structured relationship models for representation of the
      associations found.

PMID- 11461053
TI  - A comparison of the anthropometric, strength, endurance and flexibility
      characteristics of female elite and recreational climbers and non-climbers.
AB  - There is limited information on the anthropometry, strength, endurance and
      flexibility of female rock climbers. The aim of this study was to compare these
      characteristics in three groups of females: Group 1 comprised 10 elite climbers
      aged 31.3 +/- 5.0 years (mean +/- s) who had led to a standard of 'hard very
      severe'; Group 2 consisted of 10 recreational climbers aged 24.1 +/- 4.0 years
      who had led to a standard of 'severe'; and Group 3 comprised 10 physically active
      individuals aged 28.5 +/- 5.0 years who had not previously rock-climbed. The
      tests included finger strength (grip strength, finger strength measured on
      climbing-specific apparatus), flexibility, bent arm hang and pull-ups. Regression
      procedures (analysis of covariance) were used to examine the influence of body
      mass, leg length, height and age. For finger strength, the elite climbers
      recorded significantly higher values (P < 0.05) than the recreational climbers
      and non-climbers (four fingers, right hand: elite 321 +/- 18 N, recreational 251
      +/- 14 N, non-climbers 256 +/- 15 N; four fingers, left hand: elite 307 +/- 14 N,
      recreational 248 +/- 12 N, non-climbers 243 +/- 11 N). For grip strength of the
      right hand, the elite climbers recorded significantly higher values than the
      recreational climbers only (elite 338 +/- 12 N, recreational 289 +/- 10 N, non
      climbers 307 +/- 11 N). The results suggest that elite climbers have greater
      finger strength than recreational climbers and non-climbers.

PMID- 11461054
TI  - Effects of manipulating relative and absolute motion information during
      observational learning of an aiming task.
AB  - In the visual perception perspective of observational learning, the manipulation
      of relative and absolute motion information in visual demonstrations optimally
      directs learners' search towards appropriate task solutions. We assessed the
      effect of emphasizing transformational information and removal of structural
      information using point-light kinematic displays in approximating the model's
      relative motion patterns. Participants viewed computer-simulated point-light
      demonstrations or normal video demonstrations before and intermittently
      throughout 100 acquisition trials with knowledge of results on an underarm
      modified-dart aiming task. On the next day, all participants performed 20
      retention trials without demonstrations. The kinematics of spatial and temporal
      coordination and control variables were examined relative to the model's action,
      as well as performance scores. The results indicated that approximation of the
      model's spatial and temporal coordination and control patterns was achieved after
      observation of either type of demonstrations. No differences were found in
      movement outcomes. In a second experiment, the effects of manipulating absolute
      motion information by slow-motion demonstrations were examined relative to real
      time demonstrations. Real-time demonstrations led to a closer approximation to
      the model's spatial and temporal coordination patterns and better outcome scores,
      contradicting predictions that slow-motion displays convey intact relative motion
      information. We speculate that the effect of visual demonstration speed on action
      perception and reproduction is a function of task constraints--that is, novelty
      or familiarity of relative motion of demonstrated activities.

PMID- 11461055
TI  - Do oarsmen have asymmetries in the strength of their back and leg muscles?
AB  - The aim of this study was to establish whether asymmetry of the strength of the
      leg and trunk musculature is more prominent in rowers than in controls. Nineteen
      oarsmen and 20 male controls matched for age, height and body mass performed a
      series of isokinetic and isometric strength tests on an isokinetic dynamometer.
      These strength tests focused on the trunk and leg muscles. Comparisons of
      strength were made between and within groups for right and left symmetry
      patterns, hamstring: quadriceps ratios, and trunk flexor and extensor ratios. The
      results revealed no left and right asymmetries in either the knee extensor or
      flexor strength parameters (including both isometric and isokinetic measures).
      Knee extensor strength was significantly greater in the rowing population, but
      knee flexor strength was similar between the two groups. No difference was seen
      between the groups for the hamstring: quadriceps strength ratio. In the rowing
      population, stroke side had no influence on leg strength. No differences were
      observed in the isometric strength of the trunk flexors and extensors between
      groups, although EMG activity was significantly higher in the rowing population.
      Patterns of asymmetry of muscle activity were observed between the left and right
      erector spinae muscles during extension, which was significantly related to
      rowing side (P < 0.01). These observations could be related to the high incidence
      of low back pain in oarsmen.

PMID- 11461056
TI  - Ethics and paediatric exercise science: issues and making a submission to a local
      ethics and research committee.
AB  - Research with children presents issues beyond those normally encountered in adult
      exercise science research. This paper explores the specific ethical issues that
      are encountered when conducting paediatric research in the exercise sciences. We
      identify the historical, moral and philosophical underpinnings of ethical
      conduct. The issue of consent and children's ability to provide informed consent
      is discussed, as is the nature of therapeutic and non-therapeutic research.
      Finally, we examine the information that is required by a local ethics and
      research committee and provide guidance material to help in the formulation of an
      application to such a committee.

PMID- 11461057
TI  - An investigation of parents' attitudes to dental health and school dental
      screening.
AB  - OBJECTIVE: The aim of this study was to investigate factors that influence
      parental responses to school dental screening and dental care for their children.
      The expectations were that this study would aid reforms to the dental screening
      service. RESEARCH DESIGN: The study utilised qualitative research methodology
      involving a series of discussion groups. PARTICIPANTS: Groups were conducted
      amongst parents who resided in a deprived area of Manchester and whose children
      had recently undergone school dental screening. RESULTS: During analysis two
      distinct groups of parents emerged. The first group were regular asymptomatic
      attenders, however attitudes towards school dental screening and their subsequent
      behaviour differed within the group. The second group were irregular symptomatic
      attenders, there were also differences of opinion and behaviour towards school
      dental screening in this group. For each group there were distinct factors that
      formed the parent's response to school dental screening and attitudes to their
      child's dental attendance. CONCLUSIONS: The majority of parents supported school
      dental screening and some relied solely on screening as the source of dental care
      for their children. There was a degree of confusion as to who provided the
      service and some criticism of the communication about screening. This could
      result in conflict with GDPs and undermining of faith in the profession. Some
      parents considered dental health to be the responsibility of the child and the
      profession once children had reached the age of seven or so.

PMID- 11461058
TI  - A gender perspective of self-perceived oral health in adolescents: associations
      with attitudes and behaviours.
AB  - OBJECTIVE: To investigate the associations between dental attitudes and
      behaviours, and self-perceived oral health from a gender perspective in an
      adolescent population. DESIGN: A census survey. Self-reported questionnaires were
      answered anonymously in a standardised manner in classrooms. Attitudes studied
      included the importance of sound teeth and feelings towards visits to the
      dentist. Behaviours were represented by floss usage and sweets consumption.
      SETTING: All senior and upper secondary level schools in Skaraborg County,
      Sweden. SUBJECTS: 17,280 students, aged 13-18 years. OUTCOME MEASURES: Self
      perceived oral health, represented by a single-item rating; satisfaction with the
      appearance of the teeth; self-assessed gum bleeding; and a perceived oral health
      (POH) index. RESULTS: Recognising sound teeth as important was a predominating
      attitude among the respondents (boys 94%, girls 97%) and was significantly
      associated with a good perceived oral health overall. Individuals who experienced
      visits to dentist as unpleasant (boys 36%, girls 43%) were less likely to
      perceive good oral health as single-item rated (OR for boys 0.55[0.49, 0.63],
      girls 0.40[0.34, 0.47]). Regular use of floss had a small protective effect on
      bleeding gums. Daily sweets consumption showed a significant and inverse
      association with self-perceived oral health as single-item rated (OR for boys
      0.53[0.44, 0.66], girls 0.49[0.40, 0.60]). Girls, more often than boys, perceived
      their oral health to be good, except in the perception of the appearance of their
      teeth. CONCLUSIONS: It is concluded that the strong associations between
      attitudes and self-perceived oral health should be recognised in strategies for
      oral health promotion and that gender differences must be considered.

PMID- 11461059
TI  - Presidential address BASCD conference Durham 2001.

PMID- 11461060
TI  - Perceived disadvantages of moving community dental service functions into a
      personal dental services structure.

PMID- 11461061
TI  - Lorenz curves and their use in describing the distribution of 'the total burden'
      of dental caries in a population.
AB  - PURPOSE: 1) to describe the distribution of the total burden of dental caries in
      Danish adolescents over a 15-year period using Lorenz curves and, 2) to compare
      the observed distributions with Poisson distributions. METHOD: caries data for 15
      year-old adolescents reported to the database for the national reporting system
      for the Danish Municipal Dental Service for Children and Adolescents in 1980 (n =
      61,621) and 1995 (n = 50,359). RESULTS: The DMFS cut-off point for a given
      percentile had decreased from 1980 to 1995 and Lorenz curves showed a pattern of
      increasing inequality, even when only diseased individuals (i.e. with DMFS > or =
      1) were included. The dispersion was larger than could be expected, if caries
      developed according to a random pattern modelled by e.g. a Poisson distribution.
      CONCLUSIONS: Lorenz curves may be a useful tool in the analysis of caries data,
      with special reference to determining the appropriateness of implementing high
      risk preventive strategies.

PMID- 11461062
TI  - Factors affecting caries levels amongst 5-year-old children in County Kerry,
      Ireland.
AB  - OBJECTIVE: To investigate the factors associated with high caries levels in 5
      year-old children in the Kerry Community Care Area of the Southern Health Board
      in Ireland. DESIGN: Cross-sectional study. SETTING: County Kerry, Ireland in
      1997. SUBJECTS: A random sample of 5-year-old children. METHOD: Six hundred and
      thirty-six 5-year-old children were examined for caries following WHO diagnostic
      criteria. Information on possible caries risk factors was collected by means of a
      parental questionnaire. RESULTS: Using multivariate logistic regression analysis
      the variables most significantly associated with the presence of caries were
      water fluoridation status, whether or not the child took the baby feeding bottle
      to bed, the age at which tooth brushing started and the number of sweet snacks
      and drinks taken in a day. While there was a wide variation in caries levels
      between nine geographic areas in Co. Kerry the only significant geographic
      variation found was between fluoridated and non-fluoridated areas. CONCLUSION:
      The prevalence of dental caries amongst 5-year-old children in Co. Kerry was
      highest in those residing in non-fluoridated communities, in those who took a
      baby feeding bottle to bed, in those who did not commence tooth brushing until
      after two years of age and in those who had sweet snacks or sweet drinks between
      meals three or more times per day.

PMID- 11461063
TI  - An application of multilevel modelling to longitudinal periodontal research data.
AB  - OBJECTIVE: To introduce the concepts of random coefficient multilevel models
      through an application to periodontal research data. BASIC RESEARCH DESIGN:
      Multilevel models with random coefficients are illustrated using periodontal data
      that comprise four levels: repeated measurements at level-1, sites at level-2,
      teeth at level-3, and subjects at level-4. The study explores random coefficient
      models--where random variation occurs about explanatory variable coefficients.
      Outcomes considered are lifetime cumulative attachment loss and pocket probing
      depth. PARTICIPANTS: The study data were taken from a survey of periodontal
      disease involving 100 white male trainee engineers aged between 16 and 20
      entering the apprentice training school at the Royal Air Force-Halton, UK.
      RESULTS: The application of multilevel modelling to longitudinal data provides a
      new way of exploring old problems. The multilevel random coefficient models
      provide an opportunity to examine the 'linear' and 'burst' theories of
      periodontal disease progression, leading to the postulation that both can be
      unified within the multilevel framework. CONCLUSIONS: The multilevel methodology
      illustrates how advances in the understanding of oral health can be achieved with
      the advent of new statistical methods

PMID- 11461064
TI  - Comparison of four composite deprivation indices and two census variables in
      predicting dental caries in 12-year-old children in Wales.
AB  - OBJECTIVE: To compare the explanatory power of four composite indices of social
      economic status in their ability to predict dental caries experience. BASIC
      RESEARCH DESIGN: A secondary analysis of Welsh BASCD survey data using ward
      aggregated dental data, census variables and composite measures of deprivation.
      CLINICAL SETTING: Examinations took place in schools. PARTICIPANTS: All 12-year
      old children examined in the 1996/97 survey. MAIN OUTCOME MEASURES: The
      explanatory variables were Jarman index, Welsh Underprivileged Area score (WUPA),
      Carstairs and Townsend indices and the outcome measure was mean DMFT. RESULTS:
      The amount of the mean DMFT explained by the explanatory variables ranged from
      62.9% with Welsh Underprivileged Area score (WUPA) in Bro Taf Health Authority to
      4.2% with the Jarman index in Dyfed-Powys health authority. Of the constituent
      parts of the composite variables only the percentage with no car appeared in the
      'top three' variables in all but one of six models. CONCLUSIONS: The composite
      indices explained very different amounts of the variation in mean DMFT between
      the different health authorities. It would be unwise to rely on any one as a
      method of predicting which sections of the population would be likely to have
      dental disease.

PMID- 11461065
TI  - Oral health status of heroin users in a rehabilitation centre in Hubei province,
      China.
AB  - OBJECTIVE: To report on the oral health of heroin users and to determine risk
      factors for oral health status. DESIGN: All heroin users at one rehabilitation
      camp received an interview using a pre-tested questionnaire from one of three
      trained interviewers and a dental examination using World Health Organization
      recommended procedures from one of three calibrated dentists. SETTING: Interviews
      and examinations were carried out at Hubei Province camp. PARTICIPANTS: All 520
      resident heroin users at the camp participated in the study. OUTCOME MEASURES:
      Oral hygiene expressed using the Debris Index; caries status by DMFT; periodontal
      status by percentage with bleeding, pocketing and calculus; mucosal status using
      standard World Health Organization criteria. RESULTS: One hundred (19%) of the
      heroin users were caries free; their mean DMFT was 4.2. The majority (92%) of the
      DMFT was decay and only a small proportion (8%) was treatment related. The
      proportion of heroin users with bleeding, calculus, shallow pocketing and deep
      pocketing was 42%, 95%, 42% and 8% respectively. The mean Debris Index score was
      3.2. Mucosal lesions were present in 31 subjects (6%). Using multivariate
      analysis, duration of heroin use and education were risk factors for DMFT, route
      of drug administration was a risk factor for calculus and gender was a risk
      factor for deep pocketing. CONCLUSIONS: There are indications of poorer
      periodontal health as well as higher caries experience in this group when
      compared to provincial dental epidemiological data. Mucosal lesions were not
      widely prevalent. Both social factors and characteristics of drug use were
      related to oral health in this group.

PMID- 11461066
TI  - Onset of and patterns of change in dental anxiety in adolescence and early
      adulthood: a birth cohort study.
AB  - OBJECTIVE: To assess the onset of and patterns of change in dental anxiety during
      adolescence and early adulthood. DESIGN: A birth cohort study of 1,037
      individuals born in Queen Mary Hospital, Dunedin, New Zealand between 1 April
      1972 and 31 March 1973. Data were collected from these individuals at birth,
      every two years between the ages of 3 and 15 and at 18, 21 and 26 years. STUDY
      MEMBERS: Data on dental anxiety were obtained at the 15, 18 and 26-year
      assessments from 678 study members. OUTCOMES: Dental anxiety was assessed using
      the Dental Anxiety Scale. Study members with a score of 13 or over were
      classified as being dentally anxious. RESULTS: The prevalence of dental anxiety
      increased from 10.6% at age 15 years to 13.3% at 18 years and 21.1% at 26 years.
      Of the 31.2% who were anxious at one or more data collection periods,
      approximately one third were anxious by the age of 15, one third became anxious
      between 16 and 18 years and one third between 18 and 26 years. High rates of
      remission were observed. Of 72 study members who were dentally anxious at 15
      years, 22% were persistent cases, anxious at all three data collection points;
      24% were recurrent cases, anxious at 26 but not anxious at 18 years; and 54% were
      remitted cases, no longer anxious at 26 years. There were no gender differences
      in the onset and course of dental anxiety over the developmental periods
      observed. CONCLUSIONS: The period of observation was one of instability with
      respect to anxiety about dental treatment. Early adulthood in particular appeared
      to be a life stage during which this population was vulnerable to the onset of
      dental anxiety. This may be related to dental disease and treatment factors, or
      changing psychological states during significant life transitions.

PMID- 11461067
TI  - A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide
      (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01).
AB  - Sequential administration of the association of 5-fluorouracil, epirubicin and
      cyclophosphamide (FEC) and paclitaxel could be better tolerated than the
      association of an anthracycline and paclitaxel while having a similar antitumour
      effect. 69 patients with advanced breast cancer previously untreated with
      anthracyclines or paclitaxel entered a phase II multicentre study in which FEC
      was followed by paclitaxel. Both regimens were administered 4 times every 21
      days. The median follow-up is 20 months and 38/69 patients have died. Grade III
      IV toxicity was acceptable. Leukopenia occurred in 26% of patients,
      thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart
      failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred
      in 9% and 4% of patients, respectively and one patient had respiratory
      hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy
      because of: treatment refusal (n = 1), cardiac toxicity (n = 1), early death
      during FEC chemotherapy (n = 1), major protocol violations (n = 4),
      hypersensitivity reaction (n = 1) and early death during paclitaxel chemotherapy
      (n = 1). The overall response rate was 65% (95% CI = 53-76), and 7% of patients
      had stable disease. Therapy was defined as having failed in 28% of patients
      because they were not evaluable (13%) or had progressive disease (15%). The
      median time to progression and survival are 13.2 and 23.5 months, respectively.
      Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic
      breast cancer who have not been previously treated with anthracyclines and/or
      taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour
      effect.

PMID- 11461068
TI  - Alterations in the insulin-like growth factor system during treatment with
      diethylstilboestrol in patients with metastatic breast cancer.
AB  - Alterations in the insulin-like growth factor (IGF)-system were evaluated in 16
      patients treated with diethylstilboestrol 5 mg 3 times daily. Fasting blood
      samples were obtained before treatment and after 2 weeks, 1 month and/or 2-3
      months on therapy. Insulin-like growth factor (IGF)-I, IGF-II, free IGF-I, IGF
      binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3 were measured by radioimmuno
      /immunoradiometric-assays. All samples were subjected to Western ligand blotting
      as well as immunoblotting for IGFBP-3. We observed a significant decrease
      (percentage of pretreatment levels with 95 confidence intervals of the mean) in
      IGF-I [2 weeks 63% (49-79); 1 month 56% (44-73); 2-3 months 66% (53-82)], IGF-II
      [2 weeks 67% (56-80); 1 month 60% (52-68); 2-3 months 64% (55-75)], free IGF-I [2
      weeks 29% (19-42); 1 month 25% (18-36); 2-3 months 31% (21-46)], IGFBP-2 [2 weeks
      53% (18-156); 1 month 69% (61-78); 2-3 months 66% (57-78)], IGFBP-3 [2 weeks 74%
      (63-85); 1 month 69% (62-76); 2-3 months 71% (63-80)], as well as IGFBP-3
      protease activity [2 weeks 71% (54-95); 1 month 78% (64-94); 2-3 months 71% (54
      93)]. Contrary, the plasma levels (percentage of pretreatment levels with 95
      confidence intervals of the mean) of IGFBP-1 [2 weeks 250% (127-495); 1 month
      173% (138-542); 2-3 months 273% (146-510)] and IGFBP-4 [2 weeks 146% (112-192); 1
      month 140% (116-169); 2-3 months 150% (114-198)] increased significantly. While
      this study confirms previous observations during treatment with oral oestrogens
      in substitution doses, the reduction in plasma IGF-II, free IGF-I, IGFBP-2 and -3
      are all novel findings. A profound decrease in free IGF-I suggests a reduced
      bioavailability of IGFs from plasma to the tissues. These observations may be of
      significance to understand the mechanisms of the antitumour effect of
      diethylstilboestrol in pharmacological doses.

PMID- 11461069
TI  - A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM
      CSF in HER2+ advanced prostate cancer.
AB  - The proto-oncogene HER2 presents a novel therapeutic target. We report results in
      25 patients with HER2+ advanced prostate cancer treated with the bispecific
      antibody MDX-H210 15 microg m(-2)by intravenous infusion plus GM-CSF 5 microg kg(
      1)day(-1)by subcutaneous injection for 4 days repeated weekly for 6 weeks.
      Patients with stable disease or better received further cycles of treatment until
      disease progression or study withdrawal. 1 patient received no treatment and 4
      received less than 1 cycle and are included in the toxicity analysis only. Median
      duration of follow up was 105+ (range 21-188) days. Toxicity was generally NCI
      CTG 0-2. There were 2 grade 4 adverse events (heart failure and dyspnoea) and 1
      grade 3 event (allergic reaction) resulting in discontinuation of the study
      medication. There were 9 further grade 3 events not resulting in trial
      withdrawal. There were no treatment-related deaths. 7/20 (35%) evaluable patients
      had a >50% PSA response of median duration 128 (range 71-184+) days. 7/12 (58%)
      patients with evaluable pain had improvements in pain scores. The PSA relative
      velocity on therapy decreased in 15/18 (83%) assessable patients compared to pre
      study. GM-CSF and MDX-H210 is active in hormone refractory prostate carcinoma
      with acceptable toxicity; further studies are warranted.

PMID- 11461070
TI  - Microdialysis and response during regional chemotherapy by isolated limb infusion
      of melphalan for limb malignancies.
AB  - This study sought to use a microdialysis technique to relate clinical and
      biochemical responses to the time course of melphalan concentrations in the
      subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous
      histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing
      regional chemotherapy by Isolated Limb Infusion (ILI). 19 patients undergoing ILI
      for treatment of various limb malignancies were monitored for intra-operative
      melphalan concentrations in plasma and, using microdialysis, in subcutaneous and
      tumour tissues. Peak and mean concentrations of melphalan were significantly
      higher in plasma than in subcutaneous or tumour microdialysate. There was no
      significant difference between drug peak and mean concentrations in interstitial
      and tumour tissue, indicating that there was no preferential uptake of melphalan
      into the tumours. The time course of melphalan in the microdialysate could be
      described by a pharmacokinetic model which assumed melphalan distributed from the
      plasma into the interstitial space. The model also accounted for the vascular
      dispersion of melphalan in the limb. Tumour response in the whole group to
      treatment was partial response: 53.8% (n = 7); complete response: 33.3% (n = 5);
      no response: 6.7% (n = 1). There was a significant association between tumour
      response and melphalan concentrations measured over time in subcutaneous
      microdialysate (P< 0.01). No significant relationship existed between the
      severity of toxic reactions in the limb or peak plasma creatine phosphokinase
      levels and peak melphalan microdialysate or plasma concentrations. It is
      concluded that microdialysis is a technique well suited for measuring
      concentrations of cytotoxic drug during ILI. The possibility of predicting actual
      concentrations of cytotoxic drug in the limb during ILI using our model opens an
      opportunity for improved drug dose calculation. The combination of predicting
      tissue concentrations and monitoring in microdialysate of subcutaneous tissue
      could help optimise ILI with regard to post-operative limb morbidity and tumour
      response.

PMID- 11461071
TI  - A descriptive study of UK cancer genetics services: an emerging clinical response
      to the new genetics.
AB  - The objective was to describe NHS cancer genetic counselling services and compare
      UK regions. The study design was a cross-sectional study over 4 weeks and
      attendee survey. The setting was 22 of the 24 regional cancer genetics services
      in the UK NHS. Participants were individuals aged over 18 attending clinics at
      these services. Outcome measures were staff levels, referral rates, consultation
      rates, follow-up plans, waiting time. There were only 11 dedicated cancer
      geneticists across the 22 centres. Referrals were mainly concerned with breast
      (63%), bowel (18%) and ovarian (12%) cancers. Only 7% of referrals were for men
      and 3% were for individuals from ethnic minorities. Referral rates varied from 76
      to 410 per million per annum across the regions. Median waiting time for an
      initial appointment was 19 weeks, ranging across regions from 4 to 53 weeks.
      Individuals at population-level genetic risk accounted for 27% of consultations
      (range 0%, 58%). Shortfalls in cancer genetics staff and in the provision of
      genetic testing and cancer surveillance have resulted in large regional
      variations in access to care. Initiatives to disseminate referral and management
      guidelines to cancer units and primary care should be adequately resourced so
      that clinical genetics teams can focus on the genetic testing and management of
      high-risk families.

PMID- 11461072
TI  - Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a
      UK Caucasian population.
AB  - There is increasing evidence that vitamin D can protect against breast cancer.
      The actions of vitamin D are mediated via the vitamin D receptor (VDR). We have
      investigated whether polymorphisms in the VDR gene are associated with altered
      breast cancer risk in a UK Caucasian population. We recruited 241 women following
      a negative screening mammogram and 181 women with known breast cancer. The VDR
      polymorphism Bsm I, an intronic 3' gene variant, was significantly associated
      with increased breast cancer risk: odds ratio bb vs BB genotype = 2.32 (95% CI,
      1.23-4.39). The Bsm I polymorphism was in linkage disequilibrium with a candidate
      translational control site, the variable length poly (A) sequence in the 3'
      untranslated region. Thus, the 'L' poly (A) variant was also associated with a
      similar breast cancer risk. A 5' VDR gene variant, Fok I, was not associated with
      breast cancer risk. Further investigations into the mechanisms of interactions of
      the VDR with other environmental and/or genetic influences to alter breast cancer
      risk may lead to a new understanding of the role of vitamin D in the control of
      cellular and developmental pathways.

PMID- 11461073
TI  - A novel deletion mutation of the EXT2 gene in a large Chinese pedigree with
      hereditary multiple exostosis.
AB  - Hereditary multiple exostoses (EXT) is an autosomal dominant disease
      characterized by the formation of cartilage-capped prominences (exostoses) that
      develop from the juxta-epiphyseal regions of the long bones. 3 genes are known to
      be involved in the formation of exostoses. Among them, EXT1 and EXT2, which
      encode enzymes that catalyse the biosynthesis of heparan sulfate, an important
      component of the extracellular matrix, are responsible for over 70% of the EXT
      cases. A large Chinese family with hereditary multiple exostoses has been
      analysed and the disease-causing mutation has been found. Blood samples were
      obtained from 69 family members, including 23 affected individuals. The EXT
      phenotype was shown to be linked to the EXT2 gene by using 2-point linkage
      analysis. After polymerase chain reaction (PCR)-single strand conformation
      polymorphism (SSCP) analysis and DNA sequencing, a previously unreported deletion
      of a G in exon 3 of EXT2 gene was observed. This deletion co-segregated with the
      disease phenotype, suggesting that it is the disease-causing mutation in this
      family. Furthermore, in at least 4 members chondrosarcoma occurred after either
      an operation or injury of the exostosis and 3 of them died of the malignancy in
      the family. Whether the operation or injury was responsible for the malignant
      transformation still needs further study.

PMID- 11461074
TI  - Genetic heterogeneity and clonal evolution in neuroblastoma.
AB  - Tumour heterogeneity and clonal evolution at the genetic level may explain the
      development of malignant or resistant disease during clinical progression of
      neuroblastoma (NB). In this report we use 1p allelic analysis and DNA ploidy to
      evaluate clonal heterogeneity and clonal selection in vivo. We studied a total of
      69 tumours from 29 patients with NB. To evaluate tumour heterogeneity and clonal
      evolution in vivo we used a panel of polymorphic allelic markers mapping to
      chromosome 1. 33 tumours from 12 patients (group 1) were obtained from different
      sites during the same surgery or at sequential surgeries without intervening
      chemotherapy to evaluate genetic heterogeneity. Paired samples from 10 patients
      (group 2) were used to evaluate clonal selection before and after chemotherapy.
      In 6 cases paired tumours and derived cell lines were studied. Analysis of DNA
      ploidy changes by karyotype, FISH and flow cytometry was performed in 15 tumours
      from 6 multiply recurred local-regional (LR) NB patients. Allelotype study
      revealed that 66% (8/12) of group 1 samples were heterogeneous, with distinct
      allelic patterns in tumour samples separated by time or location. In group 2
      allelic patterns were different in post-chemotherapy specimens in 60% (6/10). DNA
      ploidy analysis showed that pre-chemotherapy samples contained 2 distinct ploidy
      clones, one diploid and one triploid, whereas all post-chemotherapy tumor samples
      were 100% diploid. These findings suggest that NB exhibits a high degree of
      clonal heterogeneity and clonal evolution occurs during the course of therapy and
      clinical progression.

PMID- 11461075
TI  - Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich
      family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer.
AB  - By using the positional cloning gene approach, we were able to identify a novel
      gene encoding for a serine/arginine-rich protein, which appears to be the human
      homologue of the rat A1 gene. We named this new gene SR-A1. Members of the SR
      family of proteins have been shown to interact with the C-terminal domain (CTD)
      of the large subunit of RNA polymerase II and participate in pre-mRNA splicing.
      We have localized the SR-A1 gene between the known genes IRF3 and RRAS on
      chromosome 19q13.3. The novel gene spans 16.7 kb of genomic sequence and it is
      formed of 11 exons and 10 intervening introns. The SR-A1 protein is composed of
      1312 amino acids, with a molecular mass of 139.3 kDa and a theoretical
      isoelectric point of 9.31. The SR-A1 protein contains an SR-rich domain as well
      as a CTD-binding domain present only in a subset of SR-proteins. Through
      interactions with the pre-mRNA and the CTD domain of the Polymerase II, SR
      proteins have been shown to regulate alternative splicing. The SR-A1 gene is
      expressed in all tissues tested, with highest levels found in fetal brain and
      fetal liver. Our data suggest that this gene is overexpressed in a subset of
      ovarian cancers which are clinically more aggressive. Studies with the steroid
      hormone receptor-positive breast and prostate carcinoma cell lines ZR-75-1, BT
      474 and LNCaP, respectively, suggest that SR-A1 is constitutively expressed.
      Furthermore, the mRNA of the SR-A1 gene in these cell lines appears to increase
      by estrogens, androgens and glucocorticoids, and to a lesser extend by
      progestins.

PMID- 11461076
TI  - Frequent loss of expression without sequence mutations of the DCC gene in primary
      gastric cancer.
AB  - Loss of heterozygosity (LOH) on chromosome 18q21 is frequently found in various
      human cancers, suggesting the presence of tumour suppressor gene(s) in this
      chromosomal region. DCC is the most likely target of LOH because loss or
      reduction of DCC expression has been found in many types of cancers. However, few
      reports have focused on sequence mutations of this gene. We investigated sequence
      mutations and expression of DCC in primary gastric cancers. We studied mutations
      in 25 of the 29 DCC exons by PCR-SSCP in 17 primary gastric cancers exhibiting
      LOH on 18q21. No mutations of DCC were found in any of the tumours, although 78%
      (47/60) of the primary tumours showed apparent loss or reduction of DCC
      expression by immunohistochemistry. Analysis of methylation status of DCC
      revealed that methylation frequently occurred in both primary tumours (75%;
      45/60) and corresponding non-cancerous gastric mucosae (72%; 43/60). Methylated
      status of DCC was significantly correlated with the loss of DCC expression in
      primary tumours (P< 0.01). These results indicate that DCC is frequently
      silenced, probably by epigenetic mechanisms instead of sequence mutations in
      gastric cancer.

PMID- 11461077
TI  - Mutation analysis of the p73 gene in nonastrocytic brain tumours.
AB  - Loss of heterozygosity (LOH) involving the distal chromosome 1 p36 region occurs
      frequently in nonastrocytic brain tumours, but the tumour suppressor gene
      targeted by this deletion is unknown. p73 is a novel gene that has high sequence
      homology and similar gene structure to the p53 gene; it has been mapped to 1 p36,
      and may thus represent a candidate for this tumour suppressor gene. To determine
      whether p73 is involved in nonastrocytic brain tumour development, we analysed 65
      tumour samples including 26 oligodendrogliomas, 4 ependymomas, 5
      medulloblastomas, 10 meningiomas, 2 meningeal haemangiopericytomas, 2
      neurofibrosarcomas, 3 primary lymphomas, 8 schwannomas and 5 metastatic tumours
      to the brain, for p73 alterations. Characterization of allelic loss at 1 p36-p35
      showed LOH in about 50% of cases, primarily involving oligodendroglial tumours
      (22 of 26 cases analysed; 85%) and meningiomas (4 of 10; 40%). PCR-SSCP and
      direct DNA sequencing of exons 2 to 14 of p73 revealed a missense mutation in one
      primary lymphoma: a G-to-A transition, with Glu291Lys change. 8 additional cases
      displayed no tumour-specific alterations, as 3 distinct polymorphic changes were
      identified: a double polymorphic change of exon 5 was found in one ependymoma and
      both samples derived from an oligodendroglioma, as follows: a G-to-A transition
      with no change in Pro 146, and a C-to-T variation with no change in Asn 204: a
      delG at exon 3/+12 position was identified in 4 samples corresponding to 2
      oligodendrogliomas, 1 ependymoma and 1 meningioma, and a C-to-T change at exon
      2/+10 position was present in a metastatic tumour. Although both LOH at 1 p36 and
      p73 sequence changes were evidenced in 4 cases, it is difficult to establish a
      causal role of the p73 variations and nonastrocytic brain tumours development.

PMID- 11461078
TI  - Mutation analysis of the CHK2 gene in families with hereditary breast cancer.
AB  - Recently CHK2 was functionally linked to the p53 pathway, and mutations in these
      two genes seem to result in a similar Li-Fraumeni syndrome (LFS) or Li-Fraumeni
      like syndrome (LFL) multi-cancer phenotype frequently including breast cancer. As
      CHK2 has been found to bind and regulate BRCA1, the product of one of the 2 known
      major susceptibility genes to hereditary breast cancer, it also more directly
      makes CHK2 a suitable candidate gene for hereditary predisposition to breast
      cancer. Here we have screened 79 Finnish hereditary breast cancer families for
      germline CHK2 alterations. Twenty-one of these families also fulfilled the
      criteria for LFL or LFS. All families had previously been found negative for
      germline BRCA1, BRCA2 and TP53 mutations, together explaining about 23% of
      hereditary predisposition to breast cancer in our country. Only one missense-type
      mutation, Ile(157)-->Thr(157), was detected. The high Ile(157)-->
      Thr(157)mutation frequency (6.5%) observed in healthy controls and the lack of
      other mutations suggest that CHK2 does not contribute significantly to the
      hereditary breast cancer or LFL-associated breast cancer risk, at least not in
      the Finnish population. For Ile(157)--> Thr(157)our result deviates from what has
      been reported previously.

PMID- 11461079
TI  - Chromosomal imbalances associated with carcinoma in situ and associated
      testicular germ cell tumours of adolescents and adults.
AB  - Carcinoma in situ (CIS) or intratubular germ cell neoplasia is generally
      considered the precursor lesion of adult testicular germ cell tumours (TGCT). The
      chromosomal imbalances associated with CIS and the corresponding seminoma (SE) or
      nonseminoma (NS) have been determined by comparative genomic hybridization (CGH)
      analysis of microdissected material from seven cases. Significantly, the CIS
      showed no gain of 12p material whereas in the invasive components of all cases
      gain of 12p was found, in 2 cases associated with amplification of the 12p11.2
      12.1 region. Interphase fluorescence in situ analysis was consistent with this
      and provided evidence for the i(12p) or 12p11.2-12.1 amplification in the SE and
      NS but not in the corresponding CIS. This suggests a role for these changes in
      progression of CIS to invasive testicular cancer or progression of the invasive
      disease. Other imbalances such as gain of material from chromosomes 1, 5, 7, 8,
      12q and X and loss of material from chromosome 18 were frequently identified (>
      40% of cases) in the CIS associated with both SE and NS as well as in the
      invasive components. Loss of material from chromosome 4 and 13 and gain of 2p
      were more frequently found in the invasive components. The results shed light on
      the genetic relationship between the non-invasive and invasive components of
      testicular cancer and the stage at which particular chromosomal changes may be
      important.

PMID- 11461080
TI  - Expression of the normal epithelial cell-specific 1 (NES1; KLK10) candidate
      tumour suppressor gene in normal and malignant testicular tissue.
AB  - The normal epithelial cell-specific 1 (NES1) gene (official name kallikrein gene
      10; KLK10) is a new member of the expanding human kallikrein gene family and
      encodes for a secreted serine protease. Experimental evidence suggests that NES1
      controls normal cell growth and may function as a tumour suppressor. NES1 is down
      regulated during breast cancer progression. The NES1 gene is highly expressed in
      testicular as well as in other tissues. In this study, we investigated the
      expression level of the NES1 gene in cancerous and normal testicular tissues with
      reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. In all 14 primary testicular germ-cell tumours examined,
      the NES1 gene expression was markedly reduced compared to adjacent (paired)
      normal tissues. We further examined 6 randomly selected primary germ-cell tumours
      and 8 normal tissues (obtained from different individuals). We confirmed the
      differential expression of the NES1 gene in germ-cell tumours (GCT) and pre
      malignant carcinoma in situ (CIS). Our findings suggest that NES1 may act as a
      tumour suppressor and may play a role in the pathogenesis and progression of this
      malignancy.

PMID- 11461081
TI  - Growth pattern of ductal carcinoma in situ (DCIS): a retrospective analysis based
      on mammographic findings.
AB  - The aim of this study was to obtain information concerning the direction and
      rates of growth of ductal carcinoma in situ (DCIS). The previous mammograms of
      124 women diagnosed with DCIS were examined. If in retrospect calcifications were
      present on the previous examination, the exact size and position were recorded on
      both diagnostic and previous imaging. The rates of change and direction of change
      in extent of calcifications were calculated. 39 women with a diagnosis of DCIS in
      retrospect had calcifications visible on both their current and prior
      examinations; these formed the study group. For individual clusters of
      calcification, change occurred along an axis to the nipple at a mean of 5.5 mm y(
      1)and along an axis at 90 degrees to the nipple at 2.6 mm y(-1). Increase in
      calcifications along the axis to the nipple occurred at 2.6 mm y(-1)toward and
      2.8 mm y(-1)away from the nipple. Increase in the axis to the nipple occurred at
      1.8 mm y(-1)for low grade, 4.2 mm y(-1)for intermediate grade and 7.1 mm y(-1)for
      high grade. DCIS growth along an axis to the nipple occurs at over twice the rate
      of growth in the other direction(s) and growth toward and away from the nipple
      occurred equally. Growth rates increased with increasing nuclear grade of DCIS.
      These results validate nuclear grading of DCIS. Additionally, the results suggest
      that increased importance should be placed on identifying the 'nipple' and 'anti
      nipple' margins of DCIS represented by calcifications for both surgical excision
      and pathological scrutiny.

PMID- 11461082
TI  - Analysis of differentially expressed genes in human hepatocellular carcinoma
      using suppression subtractive hybridization.
AB  - The genetic basis of hepatocellular carcinoma (HCC) has not yet been fully
      understood. Although various methods have been developed to detect differentially
      expressed genes in malignant diseases, efficient analysis from clinical specimens
      is generally difficult to perform due to the requirement of a large amount of
      samples. In the present study, we analysed differentially expressed genes with a
      small amount of human HCC samples using suppression subtractive hybridization
      (SSH). Total RNA were obtained from the hepatitis C virus-associated HCC and
      adjacent non-HCC liver tissues. cDNA was synthesized using modified RT-PCR, and
      then tester cDNA was ligated with 2 different kinds of adaptors and hybridized
      with an excess amount of driver cDNA. Tester specific cDNA was obtained by
      suppression PCR and the final PCR product was subcloned and sequenced. We
      identified 7 known genes (focal adhesion kinase, deleted in colon cancer, guanine
      binding inhibitory protein alpha, glutamine synthetase, ornithine
      aminotransferase, M130, and pepsinogen C) and 2 previously unknown genes as being
      overexpressed in HCC, and 1 gene (decorin) as suppressed in HCC. Quantitative
      analysis of gene expression using quantitative RT-PCR demonstrated the
      differential expression of these genes in the original and other HCC samples.
      These findings demonstrated that it is possible to identify the previously
      unknown, differential gene expression from a small amount of clinical samples.
      Information about such alterations in gene expression could be useful for
      elucidating the genetic events in HCC pathogenesis, developing the new diagnostic
      markers, or determining novel therapeutic targets.

PMID- 11461083
TI  - Topographic analysis of K- ras mutations in histologically normal lung tissues
      and tumours of lung cancer patients.
AB  - Mutations in the K- ras gene are very common in lung tumours and are implicated
      in the development of lung cancer, but the timing of their occurrence remains
      poorly understood. We investigated K- ras mutations in cell samples
      microdissected by laser capture microscopy at multiple sites from lung tissue
      sections representing tumour tissue and matched histologically normal tissue
      obtained from 48 lung cancer patients. K- ras mutations were detected in cell
      samples from 10 of 38 (26.3%) lung adenocarcinomas and in none of the
      histologically normal or tumour cell samples taken from 10 lung squamous cell
      carcinomas. Of the K- ras mutation-positive adenocarcinomas, in 4 cases a
      mutation was found in only the tumour tissue, in 1 case a mutation was found only
      in the histologically normal tissue, and in 5 cases mutations were found in both
      the tumour tissue and histologically normal tissue. Among these 5 cases, 2 had
      identical mutations in both the tumour tissue and histologically normal tissue, 2
      had 1 mutation in the tumour tissue and 2 mutations in the histologically normal
      tissue, 1 of which was identical to the mutation found in the tumour, and 1 case
      had 2 codon 12 mutations in tumour tissue and 2 mutations, in codons 9 and 11, in
      histologically normal tissue. These results showed that K- ras mutations are
      frequent in histologically normal cells taken from outside lung adenocarcinomas
      and suggest that some of these mutations may represent early events which could
      pave the way of lung carcinogenesis.

PMID- 11461084
TI  - Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer.
AB  - Ovarian cancer is the most frequent cause of death from gynaecological
      malignancies world wide. Little improvement has been made in the long-term
      outcome of this disease, with the 5-year survival of patients only 30%. This poor
      prognosis is due to the late presentation of the disease and to the unpredictable
      response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a
      superfamily of haemoproteins, known to be involved in the metabolic activation
      and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour
      related form of cytochrome P450 which is over expressed in a wide variety of
      primary tumours of different histological type. The presence of CYP1B1 may be of
      importance in the modulation of these tumours to anti-cancer drugs. We have
      conducted a comprehensive immunohistochemical investigation, into the presence of
      cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings
      of this study are the increased expression of CYP1B1 in the majority of ovarian
      cancers investigated (92%), with a strong correlation demonstrated between CYP1B1
      expression in both primary and metastatic ovarian cancer (P = 0.005 Spearman's
      rank correlation test). In contrast no detectable CYP1B1 was found in normal
      ovary.

PMID- 11461085
TI  - Impaired FHIT expression characterizes serous ovarian carcinoma.
AB  - The FHIT (fragile histidine triad) gene on chromosome 3p14.2 is a candidate
      tumour suppressor gene. To define the role of the FHIT gene in the development of
      ovarian cancer, we have examined 33 ovarian carcinomas, 2 borderline tumours and
      10 benign adenomas for the presence of FHIT gene alterations. FHIT transcripts
      were analysed by RT-PCR and sequencing. Aberrant FHIT transcripts were observed
      in 5/33 carcinomas (15%) and in 1 of 2 borderline tumours. Loss of normal FHIT
      transcript was observed in 5/33 carcinomas (15%) but not in 2 borderline tumours
      or 10 benign adenomas. Allelic losses at D3S1300 and D3S4103, both located within
      intron 5 of FHIT, were detected in 5/24 (21%) and 5/25 (20%) informative ovarian
      carcinomas, respectively. Expression of Fhit protein was analysed by
      immunohistochemistry in 44 carcinomas, 19 borderline tumours and 16 benign
      adenomas. Loss or significantly reduced expression of Fhit protein was observed
      in 6/44 (14%) ovarian carcinomas but not in any of 19 borderline tumours or 16
      benign adenomas. The impaired Fhit protein expression was significantly
      correlated with the loss of normal FHIT transcription. Most notably, loss of
      normal FHIT transcript and impaired expression of Fhit protein occurred only in
      serous adenocarcinomas of grade 2 and 3 (5/15; 33% and 6/19; 32%, respectively).
      The present data suggest that inactivation of the FHIT gene by loss of expression
      is one of the important molecular events associated with the genesis of ovarian
      carcinoma, especially of high-grade serous carcinoma.

PMID- 11461086
TI  - The expression of vascular endothelial growth factor C and its receptors in non
      small cell lung cancer.
AB  - Expression of vascular endothelial growth factor (VEGF)-C and that of its
      receptors were assessed in non-small cell lung cancer. Immunohistochemistry
      revealed positive VEGF-C expression in 38.7% (24/62) of the patients studied. A
      significant positive correlation was found between VEGF-C in cancer cells and
      VEGF receptor-3 (VEGFR-3) in vascular endothelial cells, but not between VEGF-C
      in cancer cells and VEGFR-2 in endothelial cells. In this cohort of lung cancer
      patients, VEGF-C expression was significantly associated with lymph node
      metastasis, lymphatic vessel invasion, and worse outcomes after the operation.
      Although the independent prognostic impact of VEGF-C and VEGFR-3 was not clear,
      VEGFR-2 expression in endothelial cells retained the independency as the
      prognostic indicator. In light of these findings, we conclude that VEGF-C plays
      an important role in lymphatic invasion/metastasis and tumour progression in non
      small cell lung cancer.

PMID- 11461087
TI  - The distribution and expression of the Bloom's syndrome gene product in normal
      and neoplastic human cells.
AB  - Bloom's syndrome (BS) is an autosomal recessive disorder associated with a
      predisposition to cancers of all types. Cells from BS sufferers display extreme
      genomic instability. The BS gene product, BLM, is a 159 kDa DNA helicase enzyme
      belonging to the RecQ family. Here, we have analysed the distribution of BLM in
      normal and tumour tissues from humans using a recently characterized, specific
      monoclonal antibody. BLM was found to be localized to nuclei in normal lymphoid
      tissues, but was largely absent from other normal tissues analysed with the
      exception of the proliferating compartment of certain tissues. In contrast,
      expression of BLM was observed in a variety of tumours of both lymphoid and
      epithelial origin. A strong correlation was observed between expression of BLM
      and the proliferative status of cells, as determined by staining for markers of
      cell proliferation (PCNA and Ki67). We conclude that BLM is a proliferation
      marker in normal and neoplastic cells in vivo, and, as a consequence, is
      expressed at a higher level in tumours than in normal quiescent tissues.

PMID- 11461088
TI  - Growing vascular endothelial cells express somatostatin subtype 2 receptors.
AB  - We hypothesized that non-proliferating (quiescent) human vascular endothelial
      cells would not express somatostatin receptor subtype 2 (sst 2) and that this
      receptor would be expressed when the endothelial cells begin to grow. To test
      this hypothesis, placental veins were harvested from 6 human placentas and 2 mm
      vein disks were cultured in 0.3% fibrin gels. Morphometric analysis confirmed
      that 50-75% of cultured vein disks developed radial capillary growth within 15
      days. Sst 2 gene expression was determined by reverse transcription-polymerase
      chain reaction (RT-PCR) analysis of the RNA from veins before culture and from
      tissue-matched vein disks that exhibited an angiogenic response. The sst 2 gene
      was expressed in the proliferating angiogenic sprouts of human vascular
      endothelium. The presence of sst 2 receptors on proliferating angiogenic vessels
      was confirmed by immunohistochemical staining and in vivo scintigraphy. These
      results suggest that sst 2 may be a unique target for antiangiogenic therapy with
      sst 2 preferring somatostatin analogues conjugated to radioisotopes or cytotoxic
      agents.

PMID- 11461089
TI  - Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits
      apoptosis in human and murine mammary adenocarcinoma cells.
AB  - Tumour progression is regulated by the balance of proliferation and apoptosis in
      the tumour cell population. To date, the role of vascular endothelial growth
      factor (VEGF) in tumour growth has been attributed to the induction of
      angiogenesis. VEGF has been shown to be a survival factor for endothelial cells,
      preventing apoptosis by inducing Bcl-2 expression. In both murine (4T1) and human
      (MDA-MB-231) metastatic mammary carcinoma cell lines, we found that VEGF
      upregulated Bcl-2 expression and anti-VEGF antibodies reduced Bcl-2 expression.
      These alterations in Bcl-2 expression were reflected by the levels of tumour cell
      apoptosis. VEGF resulted in reduced tumour cell apoptosis, whereas its inhibition
      with anti-VEGF neutralizing antibodies induced apoptosis directly in tumour
      cells. Therefore, in addition to its role in angiogenesis and vessel
      permeability, VEGF acts as a survival factor for tumour cells, inducing Bcl-2
      expression and inhibiting tumour cell apoptosis.

PMID- 11461090
TI  - Photosensitization and mechanism of cytotoxicity induced by the use of ALA
      derivatives in photodynamic therapy.
AB  - The use of more lipophilic derivatives of 5-aminolevulinic acid (ALA) is expected
      to have better diffusing properties, and after conversion into the parent ALA, to
      reach a higher protoporphyrin IX (PPIX) formation rate, thus improving the
      efficacy of topical photodynamic therapy (PDT). Here we have analysed the
      behaviour of 3 ALA derivatives (ALA methyl-ester, hexyl ester and a 2-sided
      derivative) regarding PPIX formation, efficiency in photosensitizing cells and
      mechanism of cellular death. The maximum amount of porphyrins synthesized from
      0.6 mM ALA was 47 +/- 8 ng/10(5)cells. The same amount was formed by a
      concentration 60-fold lower of hexyl-ALA and 2-fold higher of methyl-ALA. The 2
      sided derivative failed to produce PPIX accumulation. Applying a 0.6 J cm(
      2)light dose, cell viability decreased to 50%. With the 1.5 J cm(-2) light dose,
      less than 20% of the cells survive, and higher light doses produced nearly total
      cell killing. Comparing the PPIX production and the induced phototoxicity, the
      more the amount of porphyrins, the greater the cellular killing, and PPIX formed
      from either ALA or ALA-esters equally sensitize the cells to photoinactivation.
      ALA-PDT treated cells exhibited features of apoptosis, independently on the pro
      photosensitizer employed. ALA-PDT can be improved with the use of ALA
      derivatives, reducing the amount of ALA necessary to induce efficient
      photosensitization.

PMID- 11461091
TI  - Ganglioside composition and histology of a spontaneous metastatic brain tumour in
      the VM mouse.
AB  - Glycosphingolipid abnormalities have long been implicated in tumour malignancy
      and metastasis. Gangliosides are a family of sialic acid-containing
      glycosphingolipids that modulate cell-cell and cell-matrix interactions.
      Histology and ganglioside composition were examined in a natural brain tumour of
      the VM mouse strain. The tumour is distinguished from other metastatic tumour
      models because it arose spontaneously and metastasizes to several organs
      including brain and spinal cord after subcutaneous inoculation of tumour tissue
      in the flank. By electron microscopy, the tumour consisted of cells (15 to 20
      microm in diameter) that had slightly indented nuclei and scant cytoplasm. The
      presence of smooth membranes with an absence of junctional complexes was a
      characteristic ultrastructural feature. No positive immunostaining was found for
      glial or neuronal markers. The total ganglioside sialic acid content of the
      subcutaneously grown tumour was low (12.6 +/- 0.9 microg per 100 mg dry wt, n = 6
      separate tumours) and about 70% of this was in the form of N-glycolylneuraminic
      acid. In contrast, the ganglioside content of the cultured VM tumour cells was
      high (248.4 +/- 4.4 microg, n = 3) and consisted almost exclusively of N
      acetylneuraminic acid. The ganglioside pattern of the tumour grown subcutaneously
      was complex, while GM3, GM2, GM1, and GD1a were the major gangliosides in the
      cultured tumour cells. This tumour will be a useful natural model for evaluating
      the role of gangliosides and other glycolipids in tumour cell invasion and
      metastasis.

PMID- 11461092
TI  - The relationship between radiation-induced G(1)arrest and chromosome aberrations
      in Li-Fraumeni fibroblasts with or without germline TP53 mutations.
AB  - We previously showed that cultured fibroblasts from patients with the cancer
      prone Li-Fraumeni (LF) syndrome, having heterozygous germline TP53 mutations,
      sustain less ionizing radiation-induced permanent G(1)arrest than normal
      fibroblasts. In contrast, fibroblast strains from LF patients without TP53
      mutations showed normal G(1)arrest. We have now investigated the relationship
      between the extent of G(1)arrest and the level of structural chromosome damage
      (mainly dicentrics, rings and acentric fragments) in cells at their first mitosis
      after G(1)irradiation, in 9 LF strains with TP53 mutations, 6 without TP53
      mutations and 7 normal strains. Average levels of damage in the mutant strains
      were 50% higher than in normals, whereas in non-mutant LF strains they were 100%
      higher. DNA double strand breaks (dsb) are known to act as a signal for p53
      dependent G(1)arrest and to be the lesions from which chromosome aberrations
      arise. These results suggest that a minimal level of dsb is required before the
      signal for arrest is activated and that p53-defective cells have a higher signal
      threshold than p53-proficient cells. Dsb that do not cause G(1)blockage can
      progress to mitosis and appear as simple deletions or interact to form exchange
      aberrations. The elevated levels in the non-mutant strains may arise from defects
      in the extent or accuracy of dsb repair. In LF cells with or without TP53
      mutations, the reduced capacity to eliminate or repair chromosomal damage of the
      type induced by ionising radiation, may contribute to cancer predisposition in
      this syndrome.

PMID- 11461093
TI  - Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and
      murine myoblasts in vitro by a proteolysis-inducing factor (PIF).
AB  - Loss of skeletal muscle is a major factor in the poor survival of patients with
      cancer cachexia. This study examines the mechanism of catabolism of skeletal
      muscle by a tumour product, proteolysis-inducing factor (PIF). Intravenous
      administration of PIF to normal mice produced a rapid decrease in body weight
      (1.55 +/- 0.12 g in 24 h) that was accompanied by increased mRNA levels for
      ubiquitin, the Mr 14 000 ubiquitin carrier-protein, E2, and the C9 proteasome
      subunit in gastrocnemius muscle. There was also increased protein levels of the
      20S proteasome core and 19S regulatory subunit, detectable by immunoblotting,
      suggesting activation of the ATP-ubiquitin-dependent proteolytic pathway. An
      increased protein catabolism was also seen in C(2)C(12)myoblasts within 24 h of
      PIF addition with a bell-shaped dose-response curve and a maximal effect at 2-4
      nM. The enhanced protein degradation was attenuated by anti-PIF antibody and by
      the proteasome inhibitors MG115 and lactacystin. Glycerol gradient analysis of
      proteasomes from PIF-treated cells showed an elevation in chymotrypsin-like
      activity, while Western analysis showed a dose-related increase in expression of
      MSSI, an ATPase that is a regulatory subunit of the proteasome, with a dose
      response curve similar to that for protein degradation. These results confirm
      that PIF acts directly to stimulate the proteasome pathway in muscle cells and
      may play a pivotal role in protein catabolism in cancer cachexia.

PMID- 11461094
TI  - Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel
      induced apoptosis in SiHa human cervical cancer cells.
AB  - We investigated the signalling pathways by which epidermal growth factor (EGF)
      modulates paclitaxel-induced apoptosis in SiHa human cervical cancer cells. SiHa
      cells exposed to paclitaxel underwent apoptosis, which was strongly inhibited by
      EGF. This inhibition of apoptosis by EGF was not altered by pharmacological
      blockade of phosphatidylinositol 3'-OH kinase (PI-3K) with the PI-3K specific
      inhibitor LY294002 or blockade of the mitogen-activated protein kinase (MAPK)
      kinase (MEK) with the MEK specific inhibitor PD98059, or by transfection of the
      cells with PI-3K or MEK dominant-negative expression vectors. EGF did not
      stimulate PI-3K/Akt, MEK/MAPK, or p38 MAPK activity in SiHa cells but did
      transiently activate the c-Jun NH2-terminal kinase (JNK). Co-exposure of SiHa
      cells to SB202190 at concentrations that inhibit JNK abolished the protective
      effect of EGF on SiHa cells against paclitaxel-induced apoptosis. Our findings
      indicate that the JNK signaling pathway plays an important role in EGF-mediated
      protection from paclitaxel-induced apoptosis in SiHa cells.

PMID- 11461095
TI  - Carotid endarterectomy; local or general anaesthesia?
AB  - OBJECTIVES: to review the evidence for theoretical and clinical benefits of local
      or general anaesthesia for carotid endarterectomy. METHODS: literature review.
      RESULTS: animal studies suggest cerebral protection by a variety of general
      anaesthetic agents but clinical evidence is lacking. There is some clinical
      evidence that normal cerebral protective reflexes are preserved with local
      anaesthesia. Shunt insertion is the most widely used method of providing cerebral
      protection with awake testing the most reliable monitoring technique for the
      identification of ischaemia. There are therefore theoretical arguments for a
      reduced risk of perioperative stroke when local anaesthesia is used and this is
      supported by a meta-analysis of non-randomised studies. Intraoperative blood
      pressure is always higher with local anaesthesia but the incidence of
      postoperative haemodynamic instability seems to be independent of anaesthetic
      technique. There is little evidence that myocardial ischaemia is more common with
      either anaesthetic technique but meta-analysis of non-randomised again suggests
      fewer cardiac complications with local anaesthesia. Cranial nerve injury and
      haematoma formation may be less common with local anaesthesia but the evidence is
      weak. There is no evidence that surgery is more difficult with local anaesthesia
      or that it is poorly tolerated by the patients. CONCLUSIONS: there are
      theoretical arguments and clinical evidence that the outcome from carotid
      endarterectomy may be better when local anaesthesia is used with no significant
      disadvantages. An appropriately designed randomised trial is required to confirm
      this.

PMID- 11461096
TI  - Patient and hospital benefits of local anaesthesia for carotid endarterectomy.
AB  - OBJECTIVES: this study reviews and compares carotid endarterectomy (CEA)
      performed under local anaesthesia (LA) with CEA performed under general
      anaesthesia (GA) in a single institution. METHODS: data were collected
      prospectively from 240 CEA procedures. 140 GA CEA procedures are compared to 100
      LA CEA procedures in terms of outcome, operative techniques, complications, and
      length of stay. RESULTS: the groups were similar for age, gender distribution and
      preoperative risk factors. There were more asymptomatic patients in the LA group.
      There were no significant differences in death, stroke or death/stroke rate
      between the two techniques. LA CEA was associated with lower shunt rate (LA 13%,
      GA 50%, p < 0.001), lower incidence of intraoperative hypotension (LA 8%, GA 40%,
      p < 0.001), decreased hospital stay (median (IQ); LA 2 (1-2), GA 3 (1-4), and a
      cost saving of pound235 per CEA procedure. CONCLUSIONS: carotid endarterectomy
      can be performed safely under local anaesthesia with the advantage that LA CEA
      enables the surgeon to monitor and selectively shunt patients more accurately. In
      addition LA CEA is associated with a shorter hospital stay and important cost
      savings.

PMID- 11461097
TI  - Cervical nerve injury after carotid endarterectomy.
AB  - OBJECTIVE: to determine the extent and direct significance of cervical nerve
      injury after carotid endarterectomy. MATERIAL AND METHODS: fifty-two patients (61
      operations) were followed by means of patient history and neurological
      examination between 3 and 55 months following carotid endarterectomy. RESULTS:
      sixteen operated sites showed normal sensitivity. Patients assessed 3-6 months
      after surgery showed on average a neurological loss of 3.4 points (scale from 0
      4). Patients assessed after 7-12 months had on average a deficit of 2.1 points.
      After 13-24 months the score was at 1.4 and after the second postoperative year
      the score yielded only 0.4 points. CONCLUSION: loss of cervical nerve sensation
      is always present after carotid endarterectomy but tends to improve with time.
      However, the timing and extent of this improvement is unpredictable. Patients are
      usually not disturbed by these changes.

PMID- 11461098
TI  - Determinants of carotid plaque instability: echoicity versus heterogeneity.
AB  - OBJECTIVE: to identify the echoicity and heterogeneity of carotid plaques
      associated with ipsilateral symptomatic and asymptomatic neurovascular
      presentations. DESIGN: cross-sectional study. MATERIALS: a total of 113 patients,
      with 127 symptomatic and asymptomatic plaques, were studied. METHODS: the duplex
      images of the plaques were analysed echoically in a computer by means of Grey
      Scale Median (GSM) [hypoechoic (low GSM), hyperechoic (high GSM)]. The presence
      or absence of at least two plaque regions within the plaque area being echoically
      uniform (no variation of echoicity), occupying each at least 10% of the plaque
      area and having GSM difference greater than the plaque GSM was evaluated to
      distinguish the heterogeneous (presence of this pattern) from the homogeneous
      (absence of this pattern) plaques. RESULTS: the symptomatic status was associated
      with plaques of low median GSM (10.5) and 88% prevalence of the homogeneous
      pattern as contrasted with the asymptomatic status that was associated with high
      median GSM (28) and 65% prevalence of the homogeneous pattern [(p=0.001 (GSM),
      p=0.003 (heterogeneity)]. CONCLUSIONS: symptomatic plaques were associated with
      hypoechoic and predominant homogeneous echo-pattern whereas the asymptomatic ones
      were associated with hyperechoic and less predominant homogeneous pattern.

PMID- 11461099
TI  - Lipid metabolism and molecular changes in normal and atherosclerotic vessels.
AB  - OBJECTIVES: a positive correlation between cholesterol esterification, acyl
      CoA:cholesterol acyltransferase (ACAT), multidrug resistance (MDR1) gene
      expression and atherosclerotic lesions has been shown in human arteries. The
      objective of this study was to map the expression of MDR1, ACAT genes and the
      cholesteryl ester content in normal, atherosclerotic and varicose human vessels.
      MATERIALS: vascular segments were obtained from seven cadaveric donors, 27
      patients undergoing vascular surgery for severe atherosclerotic disease and 11
      patients with saphenous vein varicosities. METHODS: lipid analysis and RT-PCR of
      MDR1 and ACAT mRNAs were performed. RESULTS: an increase in cholesteryl ester
      content and in ACAT and MDR1 expression was demonstrated in relation to the age
      in the arteries prone to atherosclerosis; this expression was maximal in arteries
      from symptomatic patients. In resistant arteries and in veins cholesteryl ester
      accumulation was rare and light, while ACAT and MDR1 expression was not related
      to the age of the subjects. CONCLUSIONS: the results showed that an increase in
      MDR1 and ACAT expression may be responsible for the accumulation of cholesteryl
      esters as well as for cell growth rate acceleration in vessel sites prone to
      atherosclerosis.

PMID- 11461100
TI  - Stenting for localised arterial stenoses in the aorto-iliac segment.
AB  - OBJECTIVE: to determine complications and patency following angioplasty (PTA) and
      stenting of aorto-iliac stenoses. SETTING: District General Hospital in U.K.
      DESIGN: prospective observational study. PATIENTS AND METHODS: between December
      1994 and June 2000, 50 patients (38 men), median age 64 (41-89) years underwent
      aorto-iliac stenting. A total of 61 stents were placed. Indications were
      intermittent claudication in 38 and rest pain, ulceration or gangrene in 12.
      Sites stented were aorta 11, common iliac artery 32, external iliac artery 14,
      common and external iliac arteries two. Bilateral iliac procedures were carried
      out in nine. Two stents were used to correct residual stenoses after aortic
      stenting. Some 11 recurrent stenoses were treated. The other reasons for stenting
      were residual stenoses greater than 30% after PTA, tight calcified stenoses or
      when a stenosed iliac artery was being used as a donor prior to crossover or
      femoropopliteal bypass. RESULTS: two immediate technical failures occurred due to
      malposition. Residual stenoses were corrected by PTA. Two further patients
      sustained minor complications. None of the aortic stents occluded through two
      required secondary procedures. Primary-assisted patency was thus 100% at three
      years. Primary patency following iliac stenting for claudication and critical
      ischaemia were 97% and 86% at three years respectively. CONCLUSION: PTA and
      stenting of aorto-iliac stenoses can be safely achieved with durable results.

PMID- 11461101
TI  - Subintimal angioplasty of native vessels in the management of occluded vascular
      grafts.
AB  - OBJECTIVES: to assess the results of subintimal angioplasty of native vessels in
      the presence of an occluded vascular bypass graft. DESIGN: retrospective case
      note review. MATERIALS: twelve patients presenting with symptoms of lower limb
      ischaemia who had previously undergone infra-inguinal bypass surgery and in whom
      the bypass graft had occluded. These patients were treated by attempting
      subintimal angioplasty of the occluded native vessels. RESULTS: there were seven
      technically successful procedures but after a median follow up of four weeks,
      only one case had persistent patency of the previously occluded segment.
      CONCLUSIONS: although subintimal angioplasty of occluded native vessels in the
      presence of an occluded bypass graft appears attractive, the results are
      disappointing.

PMID- 11461102
TI  - Acute intraoperative arterial elongation: an experimental study.
AB  - OBJECTIVES: small arterial defects resulting from either trauma or resection of
      an aneurysm often present difficult problems to the vascular surgeon. DESIGN: to
      demonstrate that certain arterial gaps as a result of traumatic injury or
      aneurysm resection could be closed with acute intraoperative arterial elongation.
      MATERIALS: fifteen mongrel dogs underwent acute intraoperative arterial
      elongation of the right superficial femoral artery, with the left side used for a
      control vessel. METHODS: arterial defects created surgically (median 50 (range 25
      to 60 mm) mm). Appropriate length of artery was then undermined. A Foley catheter
      was placed proximally and distally directly beneath this undermined portion of
      vessel. The vessel is lengthened following 3 expansion/relaxation cycle of Foley
      catheter. Arterial gaps were closed by end to end anastomosis. Arterial pressure
      study was performed in all vessels. RESULTS: acutely, arterial pressure
      differences proximal and distal to the anastomosis were seen only when arterial
      gaps were exceeded 55 mm. There was no occlusion either acutely or after 4 weeks
      follow-up period. Light microscopic examination of arterial specimens revealed
      partial disruption of internal elastic lamina. At the end of the follow-up
      period, formation of neointima with regeneration of the internal elastic lamina
      was demonstrated. Scanning electron microscopy revealed minimal endothelial
      denudation. CONCLUSIONS: we believe that, acute intraoperative elongation can be
      used as an alternative technique to vein grafting for the repair of small
      traumatic arterial defects in selected cases.

PMID- 11461103
TI  - Serum levels of elastin-derived peptides in patients with ruptured and
      asymptomatic abdominal aortic aneurysms.
AB  - OBJECTIVE: to determine whether serum elastin-derived peptides (S-EDP), are lower
      in patients with ruptured abdominal aortic aneurysms (rAAA) than asymptomatic
      (aAAA). MATERIALS AND METHODS: serum samples were collected preoperatively from
      45 consecutive patients with aAAA and 15 haemodynamically stable patients with
      rAAA. S-EDP (ng/ml) was measured by a competitive enzyme-linked immunosorbent
      assay (ELISA). RESULTS: S-EDP (mean +/- s.d.) was significantly lower in patients
      with rAAA (31.6 ng/ml +/- 6.8) than in patients with aAAA (39.4 ng/ml +/- 8.0
      p=0.001). CONCLUSION: patients with rAAA had significantly lower levels of S-EDP
      than patients with aAAA. The possibility that S-EDP can be used to identify
      patients at increased risk of rupture requires further investigation.

PMID- 11461104
TI  - Pathophysiology of proximal perigraft endoleak following endovascular repair of
      abdominal aortic aneurysms: a study using a flow model.
AB  - OBJECTIVE: to design a flow model to determine whether and why increased proximal
      neck angulation correlates with increased risk of proximal perigraft endoleak
      (PPE) flow. METHODS: a tapered stent-graft (Gianturco stent + Dacron) was
      deployed with proximal and distal necks made of silicone. The amount of PPE was
      measured over 30-s periods while the angulation of the proximal neck was
      increased. RESULTS: PPE flow increased significantly for angulations > or =30
      degrees. The graft was lifted off the neck wall and gaps between the stent-graft
      and the neck created. CONCLUSION: greater neck angulation increased PPE flow. The
      stent-graft was lifted off the neck and subsequent gaps created. This model could
      be used to compare available stent-grafts and to test new designs that would
      improve the seal in angulated necks.

PMID- 11461105
TI  - The impact of stent-graft development on outcome of AAA repair--a 7-year
      experience.
AB  - OBJECTIVE: to analyse the impact of stent-graft (SG) design and operator skill on
      the outcome of endovascular AAA repair. DESIGN: prospective non-randomised open.
      MATERIAL: a total of 158 patients (mean age 71) underwent SG repair. Patients
      were treated with five different types of SG: first (n =58) and second ( n =17)
      generation Ivancev-Malmo monoiliac SG (IM I and IM II respectively) combined with
      femoral-femoral crossover, Chuter bifurcated SG (n =15), Vanguard SG ( n =15) and
      the Zenith SG ( n =53). METHODS: patients underwent DSA and contrast CT
      preoperatively and were then followed with CT and digital scans. Recently, one
      change in AAA diameter and endoleaks (EL) were recorded. Mortality, complications
      and secondary interventions were recorded and life-table analysis for
      intervention-free SG survival calculated. RESULTS: immediate and late conversions
      as well as 30-day mortality were reduced for 2nd (Zenith and Vanguard) compared
      to 1st generation SG (IM I, Im II and chuter). SG migrations occurred only with
      the IM I and Chuter SG. Type I EL were significantly more common in 1st
      generation SG. First generation SG required significantly more secondary
      interventions than 2nd SG up to 20 months post-operatively. The number of
      unplanned intraoperative adjunctive manoeuvres was increased with 2nd SG.
      CONCLUSIONS: enhanced SG design has improved the probability of SG success after
      endovascular AAA repair. Better technical skills may also have contributed to
      improved results.

PMID- 11461106
TI  - Prospective evaluation of magnetic resonance imaging after endovascular treatment
      of infrarenal aortic aneurysms.
AB  - OBJECTIVES: to evaluate the sensitivity and specificity of magnetic resonance
      imaging (MRI) in the detection of type II endoleaks during follow-up after
      endovascular treatment of intra-renal aortic aneurysms. DESIGN: prospective
      study. MATERIAL AND METHODS: between March 1996 and November 1999, 31 patients
      with infra-renal aortic aneurysms who underwent stentgraft implantation were
      followed with helical CT and MRI, including magnetic resonance angiography (MRA),
      at 1 and 6 months after the procedure. Arteriography was performed between 6 and
      12 months after intervention. The parameters studied included the change in the
      maximum anteroposterior and transverse diameters, the nature of the signal on T1
      and T2 weighted sequences (homogeneous vs heterogeneous), the presence or absence
      of Gadolinium uptake on MRI or of contrast uptake on helical CT (early and late
      phases) in the sac of the aneurysm. On MRA, stentgraft patency and endoleak
      detection were studied. RESULTS: arteriography demonstrated an endoleak in 19
      patients (18 type II, and 1 type I endoleak). MRI at 6 months detected 18/19
      endoleaks on T1 weighted sequences after injection of Gadoliniumj; there were 2
      false positives. MRA sequences confirmed stentgraft patency in all patients, but
      did not diagnose type II endoleaks. Helical CT (late phase) at 6 months detected
      10/19 endoleaks; there was 1 false positive. The sensitivity of MRI after
      injection of Gadolinium and of helical CT for the detection of type II endoleaks
      were 94% and 50% (p=0.003) respectively. The mean maximal anteroposterior and
      transverse diameters were similar on MRI and on helical CT at 1 month and at 6
      months. CONCLUSION: MRI after injection of Gadolinium is more sensitive than
      helical CT in the detection of type II endoleaks after stentgraft implantation.
      Its more widespread use may permit earlier intervention in such patients.

PMID- 11461107
TI  - Thoracic aortic stent grafts--early experience from two centres using
      commercially available devices.
AB  - OBJECTIVES: open surgical intervention for aneurysms of the distal arch and
      descending thoracic aorta is associated with high morbidity and mortality. Stent
      grafts offer an attractive alternative treatment for these aneurysms. The aim of
      this study was to assess the morbidity and mortality of endovascular treatment
      for these aneurysms with stent grafts. DESIGN, PATIENTS AND METHODS: a
      prospective observational study was performed of 37 consecutive patients treated
      from July 1997 to October 2000 (30 at Guy's and St. Thomas' and 7 at Sheffield).
      Indications included degenerative aneurysms (n=18), false aneurysm (5), acute
      dissection (4), aortic transection (4), aneurysm related to previous surgery for
      coarctation (3), chronic dissection (2) and traumatic dissection (1). Nineteen
      were performed as elective and 18 as non-elective procedures. RESULTS: three non
      elective patients died in hospital (in-hospital and 30-day mortality 8%) and one
      suffered a stroke with spontaneous full recovery. No elective patient died. One
      patient with a persistent proximal endoleak required conversion to open repair at
      6 weeks. Two patients with persistent flow into the sac at 24 h spontaneously
      thrombosed at subsequent 3 month follow-up. Two further patients developed new
      distal endoleaks at 3 months and required distal extension cuffs. One patient
      died at 28 months of aortic rupture. Serial CT scans had shown prolapse of the
      stent graft into the aneurysm sac and the patient died just before planned
      endovascular repair. No patient suffered paraplegia or renal failure. Intensive
      care facilities were only required for patients who needed them preoperatively.
      CONCLUSIONS: thoracic stent grafts can be performed with low morbidity and
      mortality. They offer a realistic alternative to open surgery. Long term follow
      up is required to assess their durability.

PMID- 11461108
TI  - Examination of the apoptotic pathway and proteolysis in the pathogenesis of
      popliteal artery aneurysms.
AB  - OBJECTIVES: to investigate the role of apoptosis, expression of death-promoting
      molecules and mediators of apoptosis in the development of popliteal artery
      aneurysms. METHODS: ten popliteal artery aneurysm (PAA) specimens were obtained
      from patients undergoing elective surgical repair. Normal controls were popliteal
      arteries obtained from patients without PAA undergoing infrainguinal bypass
      surgery (n=8). Standard histochemistry techniques were used to assess elastic
      lamellae fragmentation and inflammatory infiltrate in PAA. Vascular smooth muscle
      cells (VSMC), macrophages, T lymphocytes, death-promoting molecules, CPP-32, Fas,
      p53, perforin, apoptosis-mediating Bcl-2 family proteins and apoptotic death
      substrate, poly(ADP-ribose) polymerase (PARP) were detected
      immunohistochemically. Detection of apoptosis was by TUNEL assay. Proteolytic
      activity was determined by 10% gelatin gel zymography. RESULTS: there is a
      conspicuous disruption and fragmentation of elastic lamellae in PAA as compared
      to normal arteries. Increased gelatinolytic activity was observed at 92, 84, 72
      and 67 kDa in PAA tissues. There is a significant decrease of VSMCs in the PAA
      walls (p=0.02). The control arteries had fewer CD68+ macrophages and CD3+ T cells
      in their media (p<0.01). There was a significant increase in the number of cells
      undergoing apoptosis in aneurysmal tissue than in the normal vessels, (p<0.02) as
      well as an increased expression of Bax, CPP-32, Fas, p53 and perforin.
      CONCLUSIONS: the data confirm the architectural disruption of the PAA wall and
      illustrate an apparent biological response involving inflammatory infiltrate,
      apoptosis and signalling molecules capable of initiating cell death. In addition
      to compromising the mechanical integrity of the vessel wall, VSMC loss may
      contribute to imbalance in the protein profile, accelerating extracellular matrix
      degradation that could favour PAA development.

PMID- 11461109
TI  - Trapdoor internal valvuloplasty--a new technique for primary deep vein valvular
      incompetence.
AB  - OBJECTIVES: to describe a new technique of exposure of the valve commissure,
      called the "Trapdoor" Internal Valvuloplasty (TIV), to treat primary deep vein
      valvular incompetence. MATERIAL AND METHODS: the TIV method involves partial
      transverse incisions which are joined together by a vertical incision to create a
      virtual "trapdoor" at the target vein valve, providing optimum access to repair
      the insufficient valve. In 17 consecutive patients (25 limbs) TIV has been
      successfully employed for 41 valvular repairs since August 1999. All patients had
      open non-healing or recurrent venous ulcers. RESULTS: on mean follow-up of six
      months (clinical assessment of venous ulcer healing and by colour-coded Duplex
      scans at 1, 3, 6, 9 and 12 months), of the 41 valves repaired by TIV technique,
      39 valves (95%) maintained full patency. Thirty-four valves (85%) achieved
      primarily a VCT <0.5 s without reflux at the target valves on Valsalva manoeuvre
      in the upright position. Eighty-four percent of all ulcers (n=25) healed within 8
      weeks of surgery without recurrence during the follow-up period. CONCLUSION: the
      Trapdoor Internal Valvuloplasty (TIV) represents a novel technique, which has the
      advantages of being both technically less demanding and anatomically better
      defined. Furthermore, TIV is physiologically acceptable and enables accurate
      localisation of valve cusp defects while allowing comprehensive, anatomical
      repair of valvular deficiencies.

PMID- 11461110
TI  - Retrograde stripping of recurrent varicose veins.

PMID- 11461111
TI  - Redo bypass surgery.

PMID- 11461112
TI  - The tumor suppressor ING1: structure and function.
AB  - The biological functions of the tumor suppressor ING1 have been studied
      extensively in the past 5 years since it was cloned. Of the three alternatively
      spliced forms of ING1, p24(ING1) has been the focus of much of past research.
      Information on the other currently known isoforms, p47(ING1), p32(ING1), and
      p27(ING1), has been lacking. ING1 shares many biological functions with p53. It
      has been reported to mediate growth arrest, senescence, apoptosis, anchorage
      dependent growth, and chemosensitivity. Some of these functions, such as cell
      cycle arrest and apoptosis, have been shown to be dependent on the activity of
      both ING1 and p53 proteins. In this review, we will examine what is known about
      ING1 up to this point and clarify the cloning errors originating from the
      isolation of this gene.

PMID- 11461113
TI  - Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose)
      metabolism.
AB  - Poly(ADP-ribosyl)ation is a posttranslational modification that alters the
      functions of the acceptor proteins and is catalyzed by the poly(ADP-ribose)
      polymerase (PARP) family of enzymes. Following DNA damage, activated poly(ADP
      ribose) polymerase-1 (PARP-1) catalyzes the elongation and branching of poly(ADP
      ribose) (pADPr) covalently attached to nuclear target proteins. Although the
      biological role of poly(ADP-ribosyl)ation has not yet been defined, it has been
      implicated in many important cellular processes such as DNA repair and
      replication, modulation of chromatin structure, and apoptosis. The transient
      nature and modulation of poly(ADP-ribosyl)ation depend on the activity of a
      unique cytoplasmic enzyme called poly(ADP-ribose) glycohydrolase which hydrolyzes
      pADPr bound to acceptor proteins in free ADP-ribose residues. While the PARP
      homologues have been recently reviewed, there are relatively scarce data about
      PARG in the literature. Here we summarize the latest advances in the PARG field,
      addressing the question of its putative nucleo-cytoplasmic shuttling that could
      enable the tight regulation of pADPr metabolism. This would contribute to the
      elucidation of the biological significance of poly(ADP-ribosyl)ation.

PMID- 11461114
TI  - Clonal variation in phenotype and life span of human embryonic fibroblasts (MRC
      5) transduced with the catalytic component of telomerase (hTERT).
AB  - Expression of telomerase (hTERT) in certain cell types has been shown to extend
      cellular life span without malignant transformation. We studied the phenotype of
      26 telomerase-transduced fibroblast clones (TTFC) generated from a mass culture
      of hTERT retrovirally transduced MRC-5 cells. About two-thirds of the transduced
      clones senesced at the expected time or shortly thereafter, despite high levels
      of expression of telomerase and telomere length maintenance. The remaining one
      third of the clones were "immortalized" (followed for over 200 cumulative
      population doublings). All clones maintained a nontransformed phenotype: contact
      inhibition, anchorage dependency, lack of tumor formation in nude mice, dose
      dependency to serum and growth factors, low expression of a matrix
      metalloproteinase associated with metastatic invasion (MMP-9) and high expression
      of its inhibitor TIMP-1, and no cytogenetic abnormalities by G-banding. In
      addition, fibroblast-specific biological parameters, such as colony size,
      production of collagenase, and response to MMC and gamma radiation were tightly
      regulated at the clonal and subclonal levels.

PMID- 11461115
TI  - Melanosomal pH controls rate of melanogenesis, eumelanin/phaeomelanin ratio and
      melanosome maturation in melanocytes and melanoma cells.
AB  - The skin pigment melanin is produced in melanocytes in highly specialized
      organelles known as melanosomes. Melanosomes are related to the organelles of the
      endosomal/lysosomal pathway and can have a low internal pH. In the present study
      we have shown that melanin synthesis in human pigment cell lysates is maximal at
      pH 6.8. We therefore investigated the role of intramelanosomal pH as a possible
      control mechanism for melanogenesis. To do this we examined the effect of
      neutralizing melanosomal pH on tyrosinase activity and melanogenesis in 11 human
      melanocyte cultures and in 3 melanoma lines. All melanocyte cultures (9 of 9)
      from Caucasian skin as well as two melanoma cell lines with comparable
      melanogenic activity showed rapid (within 24 h) increases in melanogenesis in
      response to neutralization of melanosomal pH. Chemical analysis of total melanin
      indicated a preferential increase in eumelanin production. Electron microscopy
      revealed an accumulation of melanin and increased maturation of melanosomes in
      response to pH neutralization. In summary, our findings show that: (i) near
      neutral melanosomal pH is optimal for human tyrosinase activity and
      melanogenesis; (ii) melanin production in Caucasian melanocytes is suppressed by
      low melanosomal pH; (iii) the ratio of eumelanin/phaeomelanin production and
      maturation rate of melanosomes can be regulated by melanosomal pH. We conclude
      that melanosomal pH is an essential factor which regulates multiple stages of
      melanin production. Furthermore, since we have recently identified that pink
      locus product (P protein) mediates neutralization of melanosomal pH, we propose
      that P protein is a key control point for skin pigmentation. We would further
      propose that the wide variations in both constitutive and facultative skin
      pigmentation seen in the human population could be associated with the high
      degree of P-locus polymorphism.

PMID- 11461116
TI  - Chemotactic factors enhance myogenic cell migration across an endothelial
      monolayer.
AB  - Recent reports revealed that myogenic progenitors, derived from either bone
      marrow or muscle can migrate into muscle tissue and participate in myofiber
      regeneration, when injected in the peripheral circulation. This observation might
      open a new strategy for the treatment of muscular dystrophies. The signals
      involved in myoblast recruitment from circulation are at present poorly
      understood. To investigate myoblast migration we used a transwell assay in which
      murine myoblasts and myogenic cell lines were seeded on microporous membrane
      covered by an endothelial monolayer and chemotactic factors were added in the
      lower chamber. We demonstrated that myoblasts are able to cross the endothelium
      and that this process can be modulated. In particular among tested factors, we
      observed a gradient of chemotactic activity as follows: HGF >> RANTES > PDGF-A >
      PDGF-B > FGF >> TNF-alpha > IFN-gamma > EGF. Endothelial and myoblast expression
      of Pax3 (a transcription factor expressed by embryonic migrating myogenic cells)
      and cytokine transcripts (TNF-alpha, IFN-gamma) was also monitored either at the
      basal level and after transmigration. We observed increased Pax3 expression after
      interaction of C2C12 myoblasts with endothelial cells. We consider that any new
      report elucidating the molecular signals involved in myoblast migration may be
      useful toward the development of systemic cellular-mediated gene therapy of
      muscle diseases.

PMID- 11461117
TI  - Functional comparison of the alpha3A and alpha3B cytoplasmic domain variants of
      the chicken alpha3 integrin subunit.
AB  - Integrin alpha3beta1 can be alternatively spliced to generate alpha3A and alpha3B
      cytoplasmic domain variants that are conserved among vertebrates. To identify
      distinct functions of these variants, we transfected cells with intact alpha3
      integrins or chimeric receptors. alpha3Abeta1 and alpha3Bbeta1 each localized to
      focal contacts in keratinocytes on an extracellular matrix rich in laminin-5, to
      which both are known to bind with high affinity. However, alpha3B accumulated
      intracellularly in keratinocytes on collagen, suggesting that laminin binding may
      stabilize alpha3Bbeta1 surface expression. Neither alpha3 cytoplasmic domain
      affected recruitment of chimeric alpha5 integrins to fibronectin-induced focal
      contacts, and either substituted for the alpha5 cytoplasmic domain in alpha5beta1
      mediated cell migration. However, the alpha5/alpha3B chimera localized to cell
      cell borders in MDCK or CHO cells to a lesser extent than did the alpha5/alpha3A
      chimera. To determine whether the alpha3 cytoplasmic domains conferred distinct
      localization to a nonintegrin protein, we transfected cells with interleukin-2
      receptor (IL-2R) chimeras containing the alpha3 cytoplasmic domains. The IL
      2R/alpha3A chimera was expressed efficiently on the cell surface, while the IL
      2R/alpha3B chimera accumulated intracellularly. Our findings suggest that the
      alpha3B cytoplasmic domain harbors a retention signal that is regulated in an
      intact integrin and can alter cell surface expression and distribution of
      alpha3beta1.

PMID- 11461118
TI  - Effects of HsRad51 overexpression on cell proliferation, cell cycle progression,
      and apoptosis.
AB  - Expression of the DNA repair and recombination protein human Rad51 (HsRad51) is
      increased in transformed cells and in cancer cell lines. In order to study the
      effects of acute HsRad51 ectopic overexpression on cell proliferation, cell cycle
      progression, and apoptosis, we generated clones of the human fibrosarcoma cell
      line HT1080 carrying a HsRad51 transgene under a repressible promoter. The
      HsRad51-overexpressing cells showed decreased plating efficiency and growth rate
      in a dose-dependent manner with regard to the degree of overexpression. An
      accumulation of HsRad51-overexpressing cells in G(2) was observed following
      release of cells after synchronization with double thymidine block. Moreover, the
      fraction of apoptotic cells measured by annexin V-FACS increased with the time of
      HsRad51 overexpression. In the light of these observations, sustained increased
      levels of HsRad51 may contribute to tumor progression by causing a selection for
      cells tolerant to the growth-suppressive and apoptosis-inducing effects of acute
      HsRad51 overexpression.

PMID- 11461119
TI  - Peroxisome proliferator-activated receptor alpha-responsive genes induced in the
      newborn but not prenatal liver of peroxisomal fatty acyl-CoA oxidase null mice.
AB  - Mice deficient in fatty acyl-CoA oxidase (AOX(-/-)), the first enzyme of the
      peroxisomal beta-oxidation system, develop specific morphological and molecular
      changes in the liver characterized by microvesicular fatty change, increased
      mitosis, spontaneous peroxisome proliferation, increased mRNA and protein levels
      of genes regulated by peroxisome proliferator-activated receptor alpha
      (PPARalpha), and hepatocellular carcinoma. Based on these findings it is proposed
      that substrates for AOX function as ligands for PPARalpha. In this study we
      examined the sequential changes in morphology and gene expression in the liver of
      wild-type and AOX(-/-) mice at Embryonic Day 17.5, and during postnatal
      development up to 2 months of age. In AOX(-/-) mice high levels of expression of
      PPARalpha-responsive genes in the liver commenced on the day of birth and
      persisted throughout the postnatal period. We found no indication of PPARalpha
      activation in the livers of AOX(-/-) mice at embryonic age E17.5. In AOX(-/-)
      mice microvesicular fatty change in liver cells was evident at 7 days. At 2
      months of age livers showed extensive steatosis and the presence in the
      periportal areas of clusters of hepatocytes with abundant granular eosinophilic
      cytoplasm rich in peroxisomes. These results suggest that the biological ligands
      for PPARalpha vis a vis substrates for AOX either are not functional in fetal
      liver or do not cross the placental barrier during the fetal development and that
      postnatally they are likely derived from milk and diet.

PMID- 11461120
TI  - MIP-1alpha induces activation of phosphatidylinositol-3 kinase that associates
      with Pyk-2 and is necessary for B-cell migration.
AB  - The chemokine macrophage inflammatory protein-1 alpha [MIP-1alpha] causes
      migration of B cells and also induces changes in antibody secretion. However, the
      signal transduction pathways leading to these phenotypic changes remain
      undefined. We have identified a signal transduction pathway initiated by MIP
      1alpha in B cells. Here we report that stimulation of tonsil B cells with MIP
      1alpha induces phosphatidylinositol 3-kinase [PI3-K] activation. Kinase activity
      was transient with peak induction occurring within 2.5 to 5 min after stimulation
      and was dose-dependent. In addition stimulation with MIP-1alpha induces tyrosine
      phosphorylation of the proline-rich tyrosine kinase Pyk-2. Immunoprecipitation
      analysis showed a constitutive association between Pyk-2 and PI3-K and
      pretreatment of MIP-1alpha-stimulated B cells with wortmannin, a specific
      inhibitor of PI3-K, resulted in a loss of PI3-K activity. The PI3-K inhibitor
      wortmannin prevented B cells from migrating in response to MIP-1alpha. Hence, PI3
      K and Pyk-2 seem to be components of a signal transduction pathway induced by
      stimulation of B cells with MIP-1alpha, and this pathway may play a role in B
      cell migration.

PMID- 11461121
TI  - The role of ERK 1/2 and p38 MAP-kinase pathways in taxol-induced apoptosis in
      human ovarian carcinoma cells.
AB  - Taxol is an anticancer agent of natural origin with significant activity against
      a number of human cancers including ovarian and breast carcinomas. Its cytotoxic
      activity has been attributed to its ability to stabilize microtubules and to
      promote microtubule assembly. Recently it has become clearer that Taxol has
      additional activities including effects in cell signaling and gene expression. We
      have shown previously that Taxol activates ERK 1/2 MAP-kinases and results in the
      formation of GRB2/SHC complexes in murine macrophage-like RAW 267.4 cells. Here
      we demonstrate that Taxol activates ERK 1/2 and p38 MAP-kinases in human ovarian
      carcinoma cells with distinct kinetics. Activation of ERK1/2 has been observed at
      low concentrations of Taxol (1-100 nM) within 0.5-6 h, whereas longer exposure(24
      h) to nanomolar concentrations of Taxol resulted in an abrogation of the ERK1/2
      phosphorylation/activation. Higher concentrations (1-10 microM) resulted in a
      sharp inhibition of ERK1/2 activity. p38 kinase was activated by high
      concentrations (1-10 microM) of Taxol within 2 h and remained active for more
      than 24 h. The kinetic studies showed that these effects of Taxol coincided with
      an inhibition of proliferation, and the onset of apoptosis. The appearance of the
      fragmented chromatin visualized by DAPI staining, and DNA fragments seen on an
      agarose gel, coincided with the decrease in ERK1/2 activation and concomitant
      increase of the level of active p38 MAPK. The inhibitor PD98059 abrogated ERK 1/2
      activation and increased the cytotoxic effect of Taxol. An inhibitor of p38
      kinase, SB203580, protected the cells partially from Taxol and, unexpectedly,
      activated ERK 1/2 kinases. We conclude that the alternative use of ERK1/2 and p38
      MAP-kinase pathways may be necessary for the transition from proliferation state
      to Taxol-induced apoptosisin human ovarian carcinoma cells.

PMID- 11461122
TI  - Calretinin and calretinin-22k increase resistance toward sodium butyrate-induced
      differentiation in CaCo-2 colon adenocarcinoma cells.
AB  - Calretinin (CR) and the alternatively spliced form calretinin-22k (CR-22k) are
      members of the EF-hand family of Ca(2+)-binding proteins (CaBPs). CR is expressed
      in more than 60% of poorly differentiated human colon tumors and both isoforms
      are present in several colon carcinoma cell lines (e.g., WiDr). They are absent
      in normal enterocytes and in well-differentiated adenocarcinoma cell lines such
      as CaCo-2. Calretinins are thought to act as Ca(2+) buffers and to be involved in
      the regulation of Ca(2+)-dependent processes. Down-regulation of calretinins in
      WiDr cells by antisense oligonucleotides leads to growth inhibition and treatment
      with sodium butyrate (NaBt, an inducer of differentiation) leads to a blockage of
      the cell cycle and, in parallel, to down-regulation of CR. It has been proposed
      that CR and/or CR-22k may be involved in maintaining the undifferentiated
      phenotype of WiDr cells and contributing to the transformation of enterocytes.
      Expression levels and distribution of CR-22k were investigated in WiDr cells. CR
      22k was down-regulated in NaBt-treated cells and the normally cytoplasmic protein
      was preferentially localized in the nucleus either as a result of translocation
      or selective nuclear maintenance, a process more pronounced than in the case of
      CR. To compare functional differences of calretinins, CR-negative Caco-2 cells
      were stably transfected with cDNAs encoding CR or CR-22k. Cell growth of CR
      transfected cells was increased, an effect that was not observed in CR-22k
      transfected ones. The CR-expressing clones were almost completely resistant to
      treatment with 0.5 mM NaBt, a concentration significantly reducing cell growth in
      control cells. The same effect was obtained in the CR-22k-expressing clones,
      although to a lesser extent. This implicates that expression of CR and/or CR-22k
      in colon tumor cells may contribute to tumorigenesis by blocking differentiation
      promoting signals.

PMID- 11461123
TI  - Dynamic reorientation of cultured cells and stress fibers under mechanical stress
      from periodic stretching.
AB  - Cell lines derived from rat aorta and frog kidney were cultured on elastic
      membrane, and mechanical stress was given to the cells by stretching the membrane
      periodically. Cell reorientation oblique to the direction of stretching occurred
      as a result of the rapid withdrawal of cell periphery located along the direction
      of stretching and gradual extension of the cell membrane toward the direction
      oblique to the direction of stretching. Dynamic reorganization of stress fibers
      in living cells was visualized by labeling stress fibers with TRITC(3)-actin or
      EGFP-tagged moesin fragments with actin-binding ability. Stress fibers aligned in
      the direction of stretching disappeared soon after the start of stretching and
      then obliquely reoriented stress fibers appeared. The stretch-induced
      reorientation of cultured cells was suppressed by an inhibitor of stretch
      activated (SA) cation channels and by a Ca(2+) chelator. However, the
      rearrangement of stress fibers was not affected by these agents. From these
      results, we suggest that Ca(2+) influx via SA channels is involved in stretch
      induced cell reorientation but stress fiber rearrangement is independent of SA
      channels. Therefore, cell reorientation does not simply depend on the arrangement
      of stress fibers but may be controlled by some additional mechanism(s) which is
      regulated by calcium signaling.

PMID- 11461124
TI  - Sequential antibiotic therapy for cost containment in the hospital setting: why
      not?
AB  - Antibiotic cost represents a significant part of hospital budgets all over the
      world. Restriction policies, however and other similar programmes intervening in
      antimicrobial prescribing have not always been successful in lowering antibiotic
      expenditure. Timely switch or sequential therapy from initial intravenous to
      subsequent equivalent oral treatment has been implemented in many institutions
      for the same purpose. Using strict criteria for optimum patient selection, switch
      therapy has been proven both effective as antimicrobial treatment and cost
      saving. As healthcare resources remain lower than needed, cost-saving policies
      become very desirable. Thus, switch therapy is expected to be more widely used,
      since it is a cost containing policy which does not compromise treatment outcome.

PMID- 11461125
TI  - Hospital infection control in Spain.

PMID- 11461126
TI  - A comparison of two methods for identifying surgical site infections following
      orthopaedic surgery.
AB  - Many infection control practitioners (ICPs) dedicate a significant amount of time
      and resources to surveillance of surgical site infections (SSIs). Alternative
      surveillance methods need to be explored to reflect the changes to the healthcare
      system and the increasing economic constraints placed on infection control units.
      This study was undertaken to compare two methods of identifying SSIs in
      orthopaedic surgery. Surveillance data collected routinely by ICPs was compared
      with data obtained from the International Classification of Disease, 9th
      Revision, Clinical Modification (ICD-9-CM) coding in the medical record.
      Concordant results between the two methods were obtained. The use of ICD-9-CM
      coding, as stored in hospital patient administration system databases, has the
      ability to enhance routine surgical site surveillance programmes. These systems
      can be used as the basis for screening large data sets for SSIs and identifying
      where SSIs resulted in patient re-admission. A reduction in the duplication of
      data and time spent by the ICP on the collection of information for surveillance
      purposes can be achieved.

PMID- 11461127
TI  - Morbidity and mortality associated with surgical site infections: results from
      the 1997-1999 INCISO surveillance.
AB  - Since 1997, a surgical-site infections (SSI) surveillance network (INCISO) has
      been implemented in volunteer general surgical units in Northern France. For
      three months each year, all patients who undergo a surgical procedure are
      consecutively reviewed for their peri-operative condition and traced for outcome
      with a 30-day follow-up. Of the 38973 surgical patients included over a three
      year period, 1344 (3.4%) developed SSI and 568 died (1.5%) including 78 with an
      SSI. Organ-space and deep incisional SSI were associated with a higher mortality
      and required re-operation more frequently than did superficial incisional SSI.
      SSI incidence and mortality varied according to the surgical procedure. SSI was a
      significant predictor of mortality, independently of NNIS risk index and other
      survival predictors. Thirty-eight percent of deaths in SSI patients were
      attributable to infection. Hence, the significant impact of SSI on mortality and
      morbidity in surgical patients is now an additional reason to reinforce
      compliance of surgical staff with preventive measures and hygiene practices.

PMID- 11461128
TI  - Patients' perceptions of methicillin-resistant Staphylococcus aureus and source
      isolation: a qualitative analysis of source-isolated patients.
AB  - A group of 19 individuals who had been infected with methicillin-resistant
      Staphylococcus aureus (MRSA) and placed in source isolation were interviewed
      about their views of MRSA infection and the experience of source isolation.
      Participants were unclear about the nature of MRSA, and generally did not
      perceive the infection to have a significant impact upon their life (either in
      terms of the presence of symptoms or in restriction of activities). Despite this,
      roughly half the sample thought that an MRSA infection was 'serious'. Only one
      participant clearly viewed their MRSA as hospital-acquired, most being uncertain
      about the mode of transmission or viewing it as unrelated to the behaviour of
      care staff. Few respondents displayed an accurate knowledge of the reasons for
      source isolation and barrier nursing. Isolation was viewed as having advantages
      and disadvantages. There was little evidence of a detrimental psychological
      effect of isolation. Patients infected with MRSA appear to understand little
      about their condition or the necessity for barrier nursing and source isolation.
      This has implications for understanding patients' adherence with infection
      control procedures.

PMID- 11461129
TI  - Neonatal intensive care unit outbreak caused by a strain of Klebsiella oxytoca
      resistant to aztreonam due to overproduction of chromosomal beta-lactamase.
AB  - Klebsiella oxytoca strains resistant to both aztreonam and ceftriaxone were
      isolated from six neonates in a neonatal intensive care unit and water reservoirs
      of two humidifiers attached to the neonatal incubators. These isolates were
      assumed to be of the same clone because they were characterized by the same
      antimicrobial susceptibility and pulsed field gel electrophoresis patterns. It
      was established that the drug resistance was attributed to overproduction of
      chromosomally encoded Kl beta-lactamase. It was determined that an isolate (K.
      oxytoca H1) contained a high enzyme concentration (27microg/100microg of protein
      in enzyme extracts), at least 27 times higher than the control K. oxytoca N1. It
      was also demonstrated that isolates had a point mutation in the - 35 concensus
      region of the promotor gene of bla(OXY-2)leading to enzyme overproduction.
      Outbreaks caused by K1 hyperproducers have not previously been described.

PMID- 11461130
TI  - Mechanisms and risk factors for infection of pulmonary artery catheters and
      introducer sheaths in cancer patients admitted to an intensive care unit.
AB  - Pulmonary artery catheters (PACs) are typically inserted for short periods, and
      the extra-luminal route is assumed to be the overriding source of contamination
      and/or infection. Our aim was to assess the incidence of PAC and introducer
      colonization in cancer patients, and to study the mechanisms and risk factors for
      infection. Patients with a Swan-Ganz catheter admitted to an intensive care unit
      were prospectively analyzed over 14 months. As soon they were no longer
      necessary, PACs and introducer sheaths were removed and cultured. We recorded the
      mean duration of placement, the number of times PACs were handled and the site of
      insertion. Seventy-nine catheters were inserted in 68 patients. The median
      (range) duration was three days (0-10) for PACs, and 3.6 days (0-18) for
      introducers. PAC and/or percutaneous introducer sheath colonization was diagnosed
      in seven patients (8.9%), but in only one case were both colonized. Colonization
      rates were 15.5 per 1000 days for PACs and 14.1 per 1000 days for introducers.
      Introducers were mainly colonized before the 5th day, while PACs were mainly
      colonized after the 5th day. No PAC or introducer-related local infection or
      bacteraemia was diagnosed. Colonization was more frequent on catheters inserted
      into the internal jugular vein. The colonization rate was 5% for PACs and
      introducers. Our findings suggest that contamination of introducers and PACs may
      be dissociated and could result from either extraluminal or endoluminal
      colonization. As three of four PAC colonizations occurred after 5 days, the
      duration of catheter placement should be considered important. There was little
      clinical impact of microbial colonization.

PMID- 11461131
TI  - A nine-year experience of immunoprophylaxis against hepatitis B virus infection
      in children with cancer: results from a single institution in Poland.
AB  - The results of a nine-year study of immunoprophylaxis against HBV infection in
      children with cancer during anticancer therapy are presented. Three hundred and
      fifty-three children entered the study. The preventive strategy involved three
      different patterns of passive and active prophylaxis. Specific anti-HBV
      immunoprophylaxis introduced simultaneously with anticancer therapy resulted in
      protection of 95.2% of children; 62% of patients produced antibodies. Long-term
      follow-up confirmed stable protection. Better results were obtained in children
      who received the last dose of vaccine after chemotherapy. The overall infection
      rate was 5.4% (19/353). Thirteen (68.4%) of the 19 infections occurred in
      patients who had not received hepatitis B immunoglobulin at the beginning of
      anticancer therapy. Children vaccinated before chemotherapy (during a neonatal
      vaccination programme) showed continuous protection after one dose of vaccine in
      94% cases. In three cases, both HBsAg and anti-HBs was observed. A preventive
      strategy for viral hepatitis in children with cancer that includes passive and
      active HBV immunoprophylaxis from the beginning of chemotherapy is effective.

PMID- 11461132
TI  - Comparison of microbial contamination of enteral feeding solution between
      repeated use of administration sets after washing with water and after washing
      followed by disinfection.
AB  - We compared microbial contamination of in-use enteral feeding solution from
      repeatedly used administration sets (a delivery bag and an infusion tube) after
      washing with water or washing followed by disinfection. In eight hospitals where
      administration sets were re-used after washing with water, residual solution was
      collected from both the delivery bag and the distal end of the infusion tube
      immediately after use and the microbial contamination level and microbial species
      found examined. The residual enteral feeding solution (28 samples) in the
      delivery bag grew 10(2)-10(8) colony forming units (cfu)/mL and 36 samples from
      the distal end of the infusion tube grew 10(2)-10(9) cfu/mL. Re-processing was
      changed to washing with water followed by disinfection with 0.1% (100 ppm) sodium
      hypochlorite, and similar examinations were performed. The residual solutions in
      the bag (22 samples) and in the distal end of the infusion tube (24 samples) were
      contaminated with < 10(1)-10(4) cfu/mL each, a significant decrease (P < 0.01,
      Wilcoxon U-test) compared with washing with water alone.

PMID- 11461133
TI  - The usefulness of masks in preventing transient carriage of epidemic methicillin
      resistant Staphylococcus aureus by healthcare workers.
AB  - We assessed the usefulness of wearing masks in preventing epidemic methicillin
      resistant Staphylococcus aureus (EMRSA) carriage in nursing and physiotherapy
      staff on two dedicated EMRSA units. In the first phase of the study, members of
      staff were screened for EMRSA carriage immediately before and after periods of
      duty using nose, throat and hand swabs. During the second phase of the study,
      masks were worn by staff carrying out procedures associated with significant
      EMRSA exposure and examined for EMRSA as described for the first phase. Both
      phases were conducted over a period of two months. Forty-eight percent of nursing
      staff were colonized with EMRSA at some time during the first phase of the study.
      Wearing masks significantly reduced nasal, throat and hand carriage of EMRSA (P=
      0.05). We conclude that the wearing of masks by healthcare workers performing
      certain activities for EMRSA positive patients may prevent transient colonization
      and hence may be a useful intervention in the control of EMRSA in the hospital
      environment.

PMID- 11461134
TI  - Build your own infection control link nurse: an innovative study day.
AB  - Infection control is everyone's business and it is important that all members of
      staff observe good infection control practice. An effective infection control
      link nurse system has been shown to support and develop this approach. The
      strength of ward-based infection control link nurses depends upon their
      effectiveness as role models and their ability to influence practice on their
      wards and beyond. In addition, the degree of respect they command from their
      peers and colleagues and the amount and quality of knowledge they possess is
      crucial. This paper describes an innovative approach taken in Mid-Essex, which
      allowed infection control link nurses to assess their capabilities and
      limitations in communicating with and influencing colleagues. In addition, we
      show how quantitative measures may be made available by this approach. Such
      measures may be used to explain to management how particular areas of infection
      control practice (e.g. the need for infection control link nurses to have more
      authority and more 'muscle') may be important.

PMID- 11461135
TI  - The epic project: developing national evidence-based guidelines for preventing
      healthcare associated infections.

PMID- 11461136
TI  - Retrospective evidence for nosocomial Listeria infection.

PMID- 11461137
TI  - Selective decontamination of the digestive tract.

PMID- 11461138
TI  - Outbreak of Salmonella enteritidis gastrointestinal infections among medical
      staff due to contaminated food prepared outside the hospital.

PMID- 11461139
TI  - Carriage of methicillin-resistant Staphylococcus aureus (MRSA) after discharge
      from hospital: follow-up for how long? A Dutch multi-centre study.

PMID- 11461141
TI  - 13C metabolic flux analysis.
AB  - Metabolic flux analysis using 13C-labeled substrates has become an important tool
      in metabolic engineering. It allows the detailed quantification of all
      intracellular fluxes in the central metabolism of a microorganism. The method has
      strongly evolved in recent years by the introduction of new experimental
      procedures, measurement techniques, and mathematical data evaluation methods.
      Many of these improvements require advanced skills in the application of nuclear
      magnetic resonance and mass spectrometry techniques on the one hand and
      computational and statistical experience on the other hand. This minireview
      summarizes these recent developments and sketches the major practical problems.
      An outlook to possible future developments concludes the text.

PMID- 11461142
TI  - The silicon cell, not dead but live!

PMID- 11461143
TI  - Glucose metabolism and regulation of glycolysis in Lactococcus lactis strains
      with decreased lactate dehydrogenase activity.
AB  - The distribution of carbon flux at the pyruvate node was investigated in
      Lactococcus lactis under anaerobic conditions with mutant strains having
      decreased lactate dehydrogenase activity. Strains previously selected by random
      mutagenesis by H. Boumerdassi, C. Monnet, M. Desmazeaud, and G. Corrieu (Appl.
      Environ. Microbiol. 63, 2293-2299, 1997) were found to have single punctual
      mutations in the ldh gene and presented a high degree of instability. The strain
      L. lactis JIM 5711 in which lactate dehydrogenase activity was diminished to less
      than 30% of the wild type maintained homolactic metabolism. This was due to an
      increase in the intracellular pyruvate concentration, which ensures the
      maintained flux through the lactate dehydrogenase. Pyruvate metabolism was linked
      to the flux limitation at the level of glyceraldehyde-3-phosphate dehydrogenase,
      as previously postulated for the parent strain (C. Garrigues, P. Loubiere, N. D.
      Lindley, and M. Cocaign-Bousquet (1997) J. Bacteriol. 179, 5282-5287, 1997).
      However, a strain (L. lactis JIM 5954) in which the ldh gene was interrupted
      reoriented pyruvate metabolism toward mixed metabolism (production of formate,
      acetate, and ethanol), though the glycolytic flux was not strongly diminished.
      Only limited production of acetoin occurred despite significant overflow of
      pyruvate. Intracellular metabolite profiles indicated that the in vivo
      glyceraldehyde-3-phosphate dehydrogenase activity was no longer flux limiting in
      the Deltaldh strain. The shift toward mixed acid fermentation was correlated with
      the lower intracellular trioses phosphate concentration and diminished allosteric
      inhibition of pyruvate formate lyase.

PMID- 11461144
TI  - Accumulation of methylglyoxal in anaerobically grown Escherichia coli and its
      detoxification by expression of the Pseudomonas putida glyoxalase I gene.
AB  - Anaerobic glycerol fermentation by Escherichia coli strains expressing genes from
      the Klebsiella pneumoniae dha regulon showed that cell growth and 1,3-propanediol
      (1,3-PD) production are significantly inhibited when 5 g/L or higher of glycerol
      is initially present. One reason for this inhibition may be methylglyoxal (MG)
      accumulation. Assays of both intracellular and extracellular MG levels indicated
      an accumulation of MG in anaerobic glycerol fermentation of transgenic E. coli.
      Pseudomonas putida glyoxalase I was expressed in the transgenic E. coli to
      enhance MG detoxification. The activity of glyoxalase I in the transgenic E. coli
      with the P. putida glyoxalase I under anaerobic conditions was 12-fold higher
      than that in the control cells. Compared to the control cells, the transgenic
      cells with the P. putida glyoxalase I displayed a reduction of 35-43% in
      intracellular MG and a decrease of 30% in extracellular MG. These decreases were
      statistically significant (P>94). Furthermore, the expression of the P. putida
      glyoxalase I in the transgenic E. coli markedly improved cell growth and resulted
      in a 50% increase in 1,3-PD production.

PMID- 11461145
TI  - Expression of bifunctional enzymes with xylose reductase and xylitol
      dehydrogenase activity in Saccharomyces cerevisiae alters product formation
      during xylose fermentation.
AB  - To enhance metabolite transfer in the two initial sequential steps of xylose
      metabolism in yeast, two structural genes of Pichia stipitis, XYL1 and XYL2
      encoding xylose reductase (XR) and xylitol dehydrogenase (XDH), respectively,
      were fused in frame. Four chimeric genes were constructed, encoding fusion
      proteins with different orders of the enzymes and different linker lengths. These
      genes were expressed in Saccharomyces cerevisiae. The fusion proteins exhibited
      both XR and XDH activity when XYL1 was fused downstream of XYL2. The specific
      activity of the XDH part of the complexes increased when longer peptide linkers
      were used. Bifunctional enzyme complexes, analyzed by gel filtration, were found
      to be tetramers, hexamers, and octamers. No degradation products were detected by
      Western blot analysis. S. cerevisiae strains harboring the bifunctional enzymes
      grew on minimal-medium xylose plates, and oxygen-limited xylose fermentation
      resulted in xylose consumption and ethanol formation. When a fusion protein,
      containing a linker of three amino acids, was coexpressed with native XR and XDH
      monomers in S. cerevisiae, enzyme complexes consisting of chimerical and native
      subunits were formed. The total activity of these complexes showed XR and XDH
      activities similar to the activities obtained when the monomers were expressed
      individually. Strains which coexpressed chimerical subunits together with native
      XR and XDH monomers consumed less xylose and produced less xylitol. However, the
      xylitol yield was lower in these strains than in strains expressing only native
      XR and XDH monomers, 0.55 and 0.62, respectively, and the ethanol yield was
      higher. The reduced xylitol yield was accompanied by reduced glycerol and acetate
      formation suggesting enhanced utilization of NADH in the XR reaction.

PMID- 11461146
TI  - Conversion of xylose to ethanol by recombinant Saccharomyces cerevisiae:
      importance of xylulokinase (XKS1) and oxygen availability.
AB  - The yeast Saccharomyces cerevisiae efficiently ferments hexose sugars to ethanol,
      but it is unable to utilize xylose, a pentose sugar abundant in lignocellulosic
      materials. Recombinant strains containing genes coding for xylose reductase (XR)
      and xylitol dehydrogenase (XDH) from the xylose-utilizing yeast Pichia stipitis
      have been reported; however, such strains ferment xylose to ethanol poorly. One
      reason for this may be the low capacity of xylulokinase, the third enzyme in the
      xylose pathway. To investigate the potential limitation of the xylulokinase step,
      we have overexpressed the endogenous gene for this enzyme (XKS1) in S. cerevisiae
      that also expresses the P. stipitis genes for XR and XDH. The metabolism of this
      recombinant yeast was further investigated in pure xylose bioreactor cultivation
      at various oxygen levels. The results clearly indicated that overexpression of
      XKS1 significantly enhances the specific rate of xylose utilization. In addition,
      the XK-overexpressing strain can more efficiently convert xylose to ethanol under
      all aeration conditions studied. One of the important illustrations is the
      significant anaerobic and aerobic xylose conversion to ethanol by the recombinant
      Saccharomyces; moreover, this was achieved on pure xylose as a carbon. Under
      microaerobic conditions, 5.4 g L(-1) ethanol was produced from 47 g L(-1) xylose
      during 100 h. In fed-batch cultivations using a mixture of xylose and glucose as
      carbon sources, the specific ethanol production rate was highest at the highest
      aeration rate tested and declined by almost one order of magnitude at lower
      aeration levels. Intracellular metabolite analyses and in vitro enzyme activities
      suggest the following: the control of flux in a strain that overexpresses XKS1
      has shifted to the nonoxidative steps of the pentose phosphate pathway (i.e.,
      downstream of xylose 5-phosphate), and enzymatic steps in the lower part of
      glycolysis and ethanol formation pathways (pyruvate kinase, pyruvate
      decarboxylase, and alcohol dehydrogenase) do not have a high flux control in this
      recombinant strain. Furthermore, the intracellular ATP levels were found to be
      significantly lower for the XK strain compared with either the control strain
      under similar conditions or glucose-grown Saccharomyces. The ATP : ADP ratios
      were also lower for the XK strain, especially under microaerobic conditions (0.9
      vs 6.4).

PMID- 11461147
TI  - Involvement of nitrogen metabolism in the triggering of ethanol fermentation in
      aerobic chemostat cultures of Saccharomyces cerevisiae.
AB  - We have investigated whether central nitrogen metabolism may influence the
      triggering of ethanol fermentation in Saccharomyces cerevisiae strain CEN.PK122
      grown in the presence of different N-sources (ammonia, glutamate, or glutamine)
      under conditions in which the carbon to nitrogen (C : N) ratio was varied. An
      exhaustive quantitative evaluation of yeast physiology and metabolic behavior
      through metabolic flux analysis (MFA) was undertaken. It is shown that ethanol
      fermentation is triggered at dilution rates, D (growth rate), significantly lower
      (D=0.070 and 0.074 h(-1) for glutamate and glutamine, respectively, and D=0.109
      h(-1) for ammonia) under N- than C-limitation (approximately 0.18 h(-1) for all N
      sources). A characteristic specific rate of glucose influx, q(Glc), for each N
      source at Dc, i.e., just before the onset of respirofermentative metabolism, was
      determined (approximately 2.0, 1.5, and 2.5, for ammonia, glutamate, and
      glutamine, respectively). This q(Glc) was independent of the nutritional
      limitation though dependent on the nature of the N-source. The onset of
      fermentation occurs when this "threshold q(Glc)" is overcome. The saturation of
      respiratory activity appears not to be associated with the onset of fermentation
      since q(O(2)) continued to increase after Dc. It was remarkable that under
      respirofermentative conditions in C-limited chemostat cultures, the glucose
      consumed was almost completely fermented with biomass being synthesized from
      glutamate through gluconeogenesis. The results obtained show that the enzyme
      activities involved in central nitrogen metabolism do not appear to participate
      in the control of the overflow in carbon catabolism, which is driven toward
      ethanol production. The role of nitrogen metabolism in the onset of ethanol
      fermentation would rather be realized through its involvement in setting the
      anabolic fluxes directed to nitrogenous macromolecules. It seems that nitrogen
      related anabolic fluxes would determine when the threshold glucose consumption
      rate is achieved after which ethanol fermentation is triggered.

PMID- 11461148
TI  - A universal framework for 13C metabolic flux analysis.
AB  - A general methodology is presented for the modeling, simulation, design,
      evaluation, and statistical analysis of (13)C-labeling experiments for metabolic
      flux analysis. The universal software framework 13C-FLUX was implemented to
      support all steps of this process. Guided by the example of anaplerotic flux
      determination in Corynebacterium glutamicum, the technical details of the model
      setup, experimental design, and data evaluation are discussed. It is shown how
      the network structure, the input substrate composition, the assumptions about
      fluxes, and the measurement configuration are specified within 13C-FLUX. Based on
      the network model, different experimental designs are computed depending on the
      goal of the investigations. Finally, a specific experiment is evaluated and the
      various statistical methods used to analyze the results are briefly explained.
      The appendix gives some details about the software implementation and
      availability.

PMID- 11461149
TI  - Identification of candidate genes for controlling development of the basilar pons
      by differential display PCR.
AB  - The basilar pons, a major hindbrain nucleus involved in sensory-motor
      integration, has become a model system for studying long-distance neuronal
      migration, axon-target recognition by collateral branching, and the formation of
      patterned axonal projections. To identify genes potentially involved in these
      developmental events, we have performed a differential display PCR screen
      comparing RNA isolated from the developing basilar pons with RNA obtained from
      developing cerebellum and olfactory bulb, as well as the mature basilar pons.
      Using 400 different combinations of primers, we screened more than 11,000 labeled
      DNA fragments and identified 201 that exhibited higher expression in the basilar
      pons than in the control tissues. From these, 138 distinct gene fragments were
      cloned. The differential expression of a large subset of these fragments was
      confirmed using RNase protection assays. In situ hybridization analysis revealed
      that the expression of many of these genes is limited to the basilar pons and
      only a few other brain regions, suggesting that they may play specific roles in
      pontine development.

PMID- 11461150
TI  - The subcellular distribution of GABARAP and its ability to interact with NSF
      suggest a role for this protein in the intracellular transport of GABA(A)
      receptors.
AB  - GABA(A) receptors the major sites of fast synaptic inhibition in the brain are
      composed predominately of alpha, beta, and gamma2 subunits. The receptor gamma2
      subunit interacts with a 17-kDa microtubule associated protein GABARAP, but the
      significance of this interaction remains unknown. Here we demonstrate that
      GABARAP, which immunoprecipitates with GABA(A) receptors, is not found at
      significant levels within inhibitory synapses, but is enriched within the Golgi
      apparatus and postsynaptic cisternae. We also demonstrate that GABARAP binds
      directly to N-ethylmaleimide-sensitive factor (NSF), a protein critical for
      intracellular membrane trafficking events. NSF and GABARAP complexes could be
      detected in neurons and these two proteins also colocalize within intracellular
      membrane compartments. Together our observations suggest that GABARAP may play a
      role in intracellular GABA(A) receptor transport but not synaptic anchoring, via
      its ability to interact with NSF. GABARAP may therefore have an important role in
      the production of GABAergic synapses.

PMID- 11461151
TI  - Age-dependent effects of secreted Semaphorins 3A, 3F, and 3E on developing
      hippocampal axons: in vitro effects and phenotype of Semaphorin 3A (-/-) mice.
AB  - We studied the role of Semaphorins in the formation of hippocampal connections at
      embryonic and early postnatal stages. We show that the embryonic entorhinal
      cortex has a repulsive effect on embryonic hippocampal axons that disappears
      gradually at postnatal stages. Such chemorepulsion is blocked by Neuropilin-1 and
      -2 blocking antibodies. However, at perinatal stages, the inner layers of the
      entorhinal cortex attract CA1 axons. At these stages, Sema3A and Sema3F bind
      commissural and entorhinal axons. Sema3A and Sema3F repel hippocampal axons at
      E14-P2, but not at E13. A similar spatiotemporal pattern of chemorepulsion is
      observed for Sema3A on entorhinal axons, in contrast to Sema3F, which repels
      these axons only at postnatal ages. Sema3E also repels hippocampal axons but
      exclusively at E14. We show that Sema3A and Sema3F can induce the collapse of
      hippocampal growth cones and that membrane-bound Sema3A and Sema3F can guide
      hippocampal axons in the stripe assay. In sema3A (-/-) mice, the
      entorhinohippocampal projection is largely normal although single axons innervate
      aberrantly the stratum radiatum and the hilus. Thus, the chemorepulsion evoked by
      Sema3A, Sema3E, and Sema3F is dynamically regulated in the developing hippocampal
      formation.

PMID- 11461152
TI  - Gap junctions modulate survival-promoting effects of fibroblast growth factor-2
      on cultured midbrain dopaminergic neurons.
AB  - Fibroblast growth factor 2 (FGF-2) and glial cell line-derived neurotrophic
      factor (GDNF) support survival of dopaminergic midbrain neurons. Neurons are
      coupled by gap junctions, propagating metabolites and intracellular second
      messengers possibly mediating growth factor effects. We asked, therefore, whether
      gap junctions influence the survival-promoting effects of FGF-2 and GDNF. RT-PCR,
      Western blotting, and immunocytochemistry demonstrate that FGF-2 but not GDNF
      upregulates cx43 mRNA and immunoreactivity in rat embryonic day 14 midbrain
      cultures, whereas cx26, cx32, and cx45 were unchanged. In addition, functional
      coupling as assayed by the spread of neurobiotin was increased by FGF-2.
      Furthermore, the gap junction blocker oleamide abolished survival-promoting
      effects of FGF-2 on dopaminergic midbrain neurons. Together, these results
      support a direct role of gap junction communication for survival-promoting
      effects of FGF-2 on dopaminergic midbrain neurons, making gap junction
      communication a substantial parameter for neuron survival.

PMID- 11461153
TI  - Neuromuscular junction disassembly and muscle fatigue in mice lacking
      neurotrophin-4.
AB  - Neurotrophin-4 (NT-4) is produced by slow muscle fibers in an activity-dependent
      manner and promotes growth and remodeling of adult motorneuron innervation.
      However, both muscle fibers and motor neurons express NT-4 receptors, suggesting
      bidirectional NT-4 signaling at the neuromuscular junction. Mice lacking NT-4
      displayed enlarged and fragmented neuromuscular junctions with disassembled
      postsynaptic acetylcholine receptor (AChR) clusters, reduced AChR binding, and
      acetylcholinesterase activity. Electromyographic responses, posttetanic
      potentiation, and action potential amplitude were also significantly reduced in
      muscle fibers from NT-4 knock-out mice. Slow-twitch soleus muscles from these
      mice fatigued twice as rapidly as those from wild-type mice during repeated
      tetanic stimulation. Thus, muscle-derived NT-4 is required for maintenance of
      postsynaptic AChR regions, normal muscular electrophysiological responses, and
      resistance to muscle fatigue. This neurotrophin may therefore be a key component
      of an activity-dependent feedback mechanism regulating maintenance of
      neuromuscular connections and muscular performance.

PMID- 11461154
TI  - Identification of the full-length huntingtin- interacting protein p231HBP/HYPB as
      a DNA-binding factor.
AB  - Neurodegeneration in Huntington's disease (HD) is associated with an elongated
      glutamine tract in the widely expressed huntingtin protein. Although the
      pathogenic mechanisms are still unknown, the distinct physical properties of
      mutant huntingtin in the brain suggest that other factors including huntingtin
      interacting proteins might play a specific role. We have previously identified a
      DNA-binding motif in the proximal E1A promoter of adenovirus serotype 12 as
      responsible for E1A autoregulation. Here, we identified the p231HBP protein as a
      DNA-binding factor, the C-terminal portion of which has recently been
      characterized as the huntingtin-interacting protein HYPB of unknown function. We
      have determined the full-length cDNA sequence, identified several domains
      supporting its gene regulatory functions, and mapped the HBP231 gene to
      chromosome 3p21.2-p21.3. Our results provide an interesting molecular link
      between huntingtin and a DNA-binding factor, implicating that this interaction
      might result in the alteration of cellular gene expression involved in HD
      pathogenesis.

PMID- 11461155
TI  - Regulation of alternative splicing of human tau exon 10 by phosphorylation of
      splicing factors.
AB  - Tau is a microtubule-associated protein whose transcript undergoes regulated
      splicing in the mammalian nervous system. Exon 10 of the gene is an alternatively
      spliced cassette that is adult-specific and encodes a microtubule-binding domain.
      Mutations increasing the inclusion of exon 10 result in the production of tau
      protein which predominantly contains four microtubule-binding repeats and were
      shown to cause frontotemporal dementia and parkinsonism linked to chromosome 17
      (FTDP-17). Here we show that exon 10 usage is regulated by CDC2-like kinases
      CLK1, 2, 3, and 4 that phosphorylate serine-arginine-rich proteins, which in turn
      regulate pre-mRNA splicing. Cotransfection experiments suggest that CLKs achieve
      this effect by releasing specific proteins from nuclear storage sites. Our
      results show that changing pre-mRNA-processing pathways through phosphorylation
      could be a new therapeutic concept for tauopathies.

PMID- 11461156
TI  - The contactin-related protein FAR-2 defines purkinje cell clusters and labels
      subpopulations of climbing fibers in the developing cerebellum.
AB  - FAR-2 is a novel neural member of the Ig superfamily, which is related to
      F11/F3/contactin and axonin-1/TAG-1. This protein is expressed by subpopulations
      of Purkinje cells in the chicken cerebellum and FAR-2-positive clusters of these
      neurons alternate with FAR-2-negative clusters in both tangential dimensions of
      the cerebellar cortex. Furthermore, FAR-2 is also expressed by one type of
      Purkinje cell afferents, namely, the climbing fibers, and different
      subpopulations of these axons show distinct levels of FAR-2 expression. Homology
      modeling using axonin-1 as a template reveals that the four aminoterminal Ig
      domains of FAR-2 form a compact U-shaped structure, which is likely to contain
      functionally important ligand-binding sites. FAR-2 is binding to the Ig
      superfamily protein NgCAM/L1, but not to the related receptor NrCAM, and it is
      also interacting with the modular ECM protein tenascin-R. These results suggest
      that FAR-2 may contribute to the formation of somatotopic maps of cerebellar
      afferents during the development of the nervous system.

PMID- 11461157
TI  - Developmental regulation of alphav integrins produces functional changes in
      astrocyte behavior.
AB  - To examine the role of the extracellular matrix in regulating astrocyte behavior
      we previously characterized alphav integrin expression on postnatal astrocytes in
      vitro and found that they express alphavbeta5 and alphavbeta8. Here we show that
      differentiation of immature cells into astrocytes is accompanied by developmental
      regulation of alphav integrins, downregulation of alphavbeta1 and alphavbeta8,
      and upregulation of alphavbeta5. In addition, using two previously described
      astrocyte cell lines, we found that the neurite-permissive A7 cell line expressed
      high levels of alphavbeta1 in addition to alphavbeta5 and alphavbeta8, while the
      neurite-inhibitory Neu7 cell line expressed only alphavbeta5. To examine integrin
      function we generated clones of the Neu7 cell line expressing alphavbeta1 or
      alphavbeta3 in addition to alphavbeta5. This showed that the parent Neu7 cells
      migrated more slowly than the A7 cells on fibronectin and vitronectin, but that
      Neu7 cells expressing alphavbeta1 or alphavbeta3 integrins showed enhanced
      migration on fibronectin and vitronectin, respectively. These results show that
      alphav integrin expression is regulated during astrocyte development and confirm
      an instructive role in cell migration for alphavbeta1 in embryonic cells and
      alphavbeta3 in astroglial tumors.

PMID- 11461158
TI  - Molecular diversity in zebrafish NCAM family: three members with different VASE
      usage and distinct localization.
AB  - NCAM in vertebrates and its related molecules, apCAM in Aplysia, fasciclin II in
      Drosophila, and OCAM in mammals, play key roles in various aspects of brain
      development and functions. In this study, we have identified and characterized
      three members of the NCAM gene family in zebrafish, designated as zNCAM, zOCAM,
      and zPCAM. Three molecules exhibit similar domain organization: an amino-terminal
      signal peptide, five immunoglobulin-like domains, two fibronectin type III-like
      domains, a transmembrane segment, and a carboxy-terminal cytoplasmic region. A
      novel molecule zPCAM is most closely related to zNCAM with 66% amino acid
      identity. Diversity in the extracellular region of zPCAM is generated by
      insertion of two different types of variable alternatively spliced exons. In situ
      hybridization analysis revealed that three molecules were specifically expressed
      by the central and peripheral nervous systems from early developmental stages in
      region-specific and cell-type-specific manners. For example, zPCAM showed a
      neuromere-specific segmental expression pattern, while zOCAM first appeared in
      specific clusters of secondary neurons in the forebrain. These results suggest
      that each member of the NCAM gene family plays distinct roles in the formation
      and maintenance of functional neuronal networks in the zebrafish nervous system.

PMID- 11461159
TI  - Altered central serotoninergic neurotransmission: a potential mechanism for
      profound fatigue complicating chronic hepatitis C.
AB  - Altered central neurotransmission contributes to behavioural complications of
      chronic liver disease, such as pruritus and hepatic encephalopathy. Another
      behavioural complication of chronic liver disease, including chronic hepatitis C,
      is profound fatigue. Evidence that altered serotoninergic neurotransmission
      contributes to fatigue of central origin, and relief of profound fatigue in a
      patient with chronic hepatitis C associated with long-term ondansetron therapy,
      support the hypothesis that altered central serotoninergic neurotransmission
      contributes to fatigue complicating chronic hepatitis C. Drugs that specifically
      modulate serotoninergic neurotransmission may be effective in ameliorating
      fatigue in patients with chronic hepatitis C.

PMID- 11461160
TI  - Sphingomyelin: a natural modulator of membrane homeostasis and inflammation.
AB  - Although membrane sphingomyelin (SPH) serves as the precursor for many signaling
      molecules, its presence in large amounts, and its specific localization in the
      outer monolayer of the plasma membrane suggest that it may have a cytoprotective
      function. We propose that SPH helps maintain the integrity of the plasma membrane
      by protecting phosphatidylcholine (PC) against oxidative damage and phospholipase
      degradation. Since it contains mostly saturated longchain hydrocarbon groups, we
      postulate that SPH impedes the lateral propagation of the lipid peroxides by
      decreasing membrane fluidity, while also acting as an 'insulating' molecule. By
      virtue of its structural similarity to PC, it acts as a competitive inhibitor of
      the phospholipases, which may otherwise hydrolyze PC excessively. Because
      phospholipase reaction is the rate-limiting step in eicosanoid synthesis, SPH may
      serve as an endogenous anti-inflammatory molecule.

PMID- 11461161
TI  - Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue
      syndrome and multiple chemical sensitivity via elevated nitric
      oxide/peroxynitrite.
AB  - Three types of overlap occur among the disease states chronic fatigue syndrome
      (CFS), fibromyalgia (FM), multiple chemical sensitivity (MCS) and posttraumatic
      stress disorder (PTSD). They share common symptoms. Many patients meet the
      criteria for diagnosis for two or more of these disorders and each disorder
      appears to be often induced by a relatively short-term stress which is followed
      by a chronic pathology, suggesting that the stress may act by inducing a self
      perpetuating vicious cycle. Such a vicious cycle mechanism has been proposed to
      explain the etiology of CFS and MCS, based on elevated levels of nitric oxide and
      its potent oxidant product, peroxynitrite. Six positive feedback loops were
      proposed to act such that when peroxynitrite levels are elevated, they may remain
      elevated. The biochemistry involved is not highly tissue-specific, so that
      variation in symptoms may be explained by a variation in nitric
      oxide/peroxynitrite tissue distribution. The evidence for the same biochemical
      mechanism in the etiology of PTSD and FM is discussed here, and while less
      extensive than in the case of CFS and MCS, it is nevertheless suggestive.
      Evidence supporting the role of elevated nitric oxide/peroxynitrite in these four
      disease states is summarized, including induction of nitric oxide by common
      apparent inducers of these disease states, markers of elevated nitric
      oxide/peroxynitrite in patients and evidence for an inductive role of elevated
      nitric oxide in animal models. This theory appears to be the first to provide a
      mechanistic explanation for the multiple overlaps of these disease states and it
      also explains the origin of many of their common symptoms and similarity to both
      Gulf War syndrome and chronic sequelae of carbon monoxide toxicity. This theory
      suggests multiple studies that should be performed to further test this proposed
      mechanism. If this mechanism proves central to the etiology of these four
      conditions, it may also be involved in other conditions of currently obscure
      etiology and criteria are suggested for identifying such conditions.

PMID- 11461162
TI  - Insulin secretion as a determinant of pancreatic cancer risk.
AB  - New epidemiology confirms that glucose intolerance is a risk factor for
      pancreatic cancer, and that this association cannot be accounted for by an
      adverse impact of early pancreatic cancer on beta cell function. Previous reports
      indicate that risk for pancreatic cancer is increased in adult-onset diabetics.
      Since streptozotocin diabetes inhibits carcinogen-mediated induction of
      pancreatic cancer in hamsters, the most reasonable interpretation of these
      findings is that insulin (or some other beta cell product) acts as a promoter for
      pancreatic carcinogenesis. This view is consistent with a report that human
      pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis;
      an additional possibility is that high insulin levels indirectly promote
      pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic
      actions. In international ecologic epidemiology, pancreatic cancer rates
      correlate tightly with dietary intake of animal products; this may reflect the
      fact that vegan diets are associated with low diurnal insulin secretion. There is
      also suggestive evidence that macrobiotic vegan diets, which are low in glycemic
      index, may increase mean survival time in pancreatic cancer. However, other types
      of diets associated with decreased postprandial insulin response, such as high
      protein diets or 'Mediterranean' diets high in oleic acid, may also have the
      potential for pancreatic cancer prevention. The huge increases of age-adjusted
      pancreatic cancer mortality in Japan and among African-Americans during the last
      century imply that pancreatic cancer is substantially preventable; a low-insulin
      response diet coupled with exercise training, weight control, and smoking
      avoidance, commendable for a great many other reasons, may slash pancreatic
      cancer mortality dramatically.

PMID- 11461163
TI  - The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's
      disease and in augmenting brain damage associated with cardiovascular disease.
AB  - The incidence of Alzheimer's disease (AD) increases with age and in carriers of
      the apolipoprotein E4 genotype. A relative deficiency of vitamin K, affecting the
      extrahepatic functions of the vitamin, is common in ageing men and women. The
      concentration of vitamin K is lower in the circulating blood of APOE4 carriers
      than in that of persons with other APOE genotypes. Evidence is accumulating that
      vitamin K has important functions in the brain, including the regulation of
      sulfotransferase activity and the activity of a growth factor/tyrosine kinase
      receptor (Gas 6/Axl). The hypothesis is now proposed that vitamin K deficiency
      contributes to the pathogenesis of AD and that vitamin K supplementation may have
      a beneficial effect in preventing or treating the disease. Vitamin K may also
      reduce neuronal damage associated with cardiovascular disease.

PMID- 11461164
TI  - Alzheimer's disease: roles for mitochondrial damage, the hydroxyl radical, and
      cerebrospinal fluid deficiency of melatonin.
AB  - A deficiency of cerebrospinal fluid melatonin is postulated to be critical for
      the development of Alzheimer's disease. Some melatonin is normally secreted
      directly into the fluid inducing higher levels than in simultaneously sampled
      blood. Melatonin is carried into the ventricular system via choroid plexus
      portals. The neurohormone is a potent antioxidant that passes through cell
      membranes with ease and is concentrated in mitochondria. Neural tissue in contact
      with the ventricular system will have high levels of cellular melatonin. In
      Alzheimer's disease, inadequate melatonin allows hydroxyl radicals produced by
      mitochondrial complex IV to damage mitochondria and initiate a cascade of oxygen
      radicals that causes the neuropathological changes in Alzheimer's disease.
      Results from initial therapeutic trials of melatonin in Alzheimer's disease
      patients have demonstrated improved function, decreased 'sundowning', improved
      sleep, and a significant slowing of the progression of the disease.

PMID- 11461165
TI  - Model of interstitial pressure as a result of cyclical changes in the capillary
      wall fluid transport.
AB  - Reported interstitial pressures range from -8 to +6 mm Hg in different tissues
      and from <-20 mm Hg in burned tissue or more than +30 mm Hg in tumors. We have
      tried to link interstitial pressure to the here proposed cyclical changes in the
      fluid transport across the capillary wall. In the presented model interstitial
      pressure is considered as an average of pressures in numerous pericapillary
      spaces. A single pericapillary pressure is a dynamic difference between the net
      outward (hydraulic pressure+interstitial colloid osmotic pressure) and inward
      (plasma colloid oncotic pressure) forces. Hence, dominating net outward forces
      would result in a positive pericapillary interstitial pressure, while stronger
      inward forces would produce negative pressures in the pericapillary space. All
      interruptions of blood flow leave some blood in capillaries with a normal oncotic
      pressure and no hydrostatic pressure that might act as a strong absorber of
      interstitial fluid until the blood flow is reestablished. Model assumptions for
      the systemic circulation capillaries include (a) precapillary sphincters can
      almost entirely stop the capillary flow, (b) only a minority of sphincters are
      normally open in the tissue, and (c) hydrostatic pressures in unperfused
      capillaries are similar to the pressures at their venous ends. The key proposal
      is that capillaries with closed precapillary sphincters along their entire length
      have low hydrostatic pressure of 10 to 15 mm Hg. This pressure cannot force
      filtration, so these capillaries reabsorb interstitial fluid from the
      pericapillary space along their entire length. In the open capillaries,
      hydrostatic pressure filtrates fluid to the pericapillary space along most of
      their length. Fluid enters, moves some 20 or 30 micrometers away and back to be
      reabsorbed at the same point. Closed periods are periods of intense fluid
      reabsorption, while the short open periods refill the space with fresh fluid. It
      can be calculated that subcutaneous tissue interstitial pressure values might
      develop if the closed periods are 1.14 to 2.66 times longer than the open
      periods. Positive interstitial pressures observed in some organs might develop if
      open periods are longer than the closed periods. High interstitial colloid
      pressure in lungs makes both perfused and unperfused capillaries absorptive,
      resulting in more negative values of lung interstitial pressure. The same model
      is used to explain interstitial pressure values in tumors, burned tissue and
      intestinal villi.

PMID- 11461166
TI  - Non-steroidal anti-inflammatory drugs in chemoprevention of breast and prostate
      cancer.
AB  - Despite convincing evidence from animal experiments, epidemiological studies
      linking the use of non-steroidal anti-inflammatory drugs (NSAIDs) with lower risk
      of breast and prostate cancer have been equivocal. One explanation for the
      inconsistencies among epidemiological studies may relate to individual
      differences in NSAID metabolism due to genetic polymorphisms in enzymes such as N
      -acetyltransferases and cytochrome P4502C9, which are known to be involved in the
      metabolic biotransformation of NSAIDs. The exclusion of these molecular
      biomarkers of individual susceptibility may have contributed to the inconsistent
      findings on the effects of NSAIDs in breast and prostate cancer.

PMID- 11461167
TI  - Mortality from Western cancers rose dramatically among African-Americans during
      the 20th century: are dietary animal products to blame?
AB  - Statistics compiled by the National Cancer Institute indicate that, between 1935
      and 1974, age-adjusted mortality from most 'Western' cancers (those of the
      breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in
      African-Americans. This phenomenon is paralleled by marked increases in the
      incidence of these cancers in Asia and Southern Europe during the latter 20th
      century, in conjunction with increased intakes of dietary animal products. A
      credible case can be made that diets rich in animal products work in various
      complementary ways to up-regulate serum levels of insulin, free IGF-I, and free
      sex hormones: hormones that appear to have important promotional activity for
      Western cancers. It seems likely that dietary animal product intake by black
      Americans increased substantially during the 20th century, and that this fact is
      primarily responsible for their concurrent marked increase in mortality from
      Western cancers. A whole-food vegan diet rich in fruits and vegetables,
      especially if coupled with regular exercise and smoking avoidance, could be
      expected to have a remarkably positive impact on African-American cancer risk,
      reversing the increases in cancer risk incurred during the 20th century.

PMID- 11461168
TI  - Involvement of cerebrovascular semicarbazide-sensitive amine oxidase in the
      pathogenesis of Alzheimer's disease and vascular dementia.
AB  - Fibrillary tangles and senile plaques resulting from advanced aggregation of beta
      amyloid and other proteins are pathological characteristics of Alzheimer's
      disease (AD). Cerebral amyloid angiopathy is quite common in AD. In fact, amyloid
      fibrils fuse to and emanate from the vascular basement membrane. Semicarbazide
      sensitive amine oxidase (SSAO), located in outer membranes of vascular smooth
      muscles and endothelia, catalyzes deamination of methylamine-producing
      formaldehyde and hydrogen peroxide. SSAO is also involved in lymphocyte adhesion
      and is up-regulated in response to inflammation. SSAO-mediated generation of
      formaldehyde can induce protein (i.e. beta-amyloid) cross-linkage, deposition and
      subsequently plaque formation in the compartment adjacent to the cerebrovessels.
      Formaldehyde may cause cytotoxicity, which induces inflammation and release of
      more SSAO, producing a cascade of toxic cycle. Increased SSAO-mediated reaction
      may be chronically involved in the pathogenesis of vascular dementia and AD.

PMID- 11461169
TI  - Effects of tetrahydrobiopterin on ataxia in Machado-Joseph disease may be based
      upon the theory of 'cerebellar long-term depression'.
AB  - We previously verified the effectiveness of tetrahydrobiopterin (BH4) on the
      ataxia in Machado-Joseph disease (MJD; SCA3 [spinocerebellar ataxia type 3]) as
      one of the most common types of dominantly inherited spinocerebellar ataxias. We
      hypothesized as to the pharmacological mechanism of BH4 that on the basis of
      'cerebellar long-term depression' theory, BH4 may exert its actions at the levels
      of soluble guanylate cyclase in the Purkinje cells and of nitric oxide synthase
      in the granule cells. If cerebellar long-term depression is the case as the
      theoretical basis of BH4, it will open a new page of therapeutic strategy for
      spinocerebellar ataxias.

PMID- 11461170
TI  - Can glucose-insulin-potassium regimen suppress inflammatory bowel disease?
AB  - Insulin seems to have the ability to suppress the production of tumor necrosis
      factor-alpha and superoxide anion, enhance the synthesis of nitric oxide and
      inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) through
      stimulation of nitric oxide. This suggests that insulin can behave as an anti
      inflammatory molecule. In view of this, it is suggested that insulin in
      combination with glucose and potassium may be of benefit in the management of
      inflammatory bowel disease.

PMID- 11461171
TI  - Application of genomeceuticals to the molecular and immunological aspects of
      autism.
AB  - Autism is a developmental disease affecting as many as 1 in 300 children and is
      often characterized as a mental disorder originating in infancy that is
      associated with self-absorption, inability to interact socially, behavior, and
      language dysfunction (e.g. echolalia). Current theories indicate an important
      role of diet in the development of disease. It is thought that, as a result of
      maldigestion of casein and gluten, opioid-type peptides, or exorphins, are
      produced. Additionally, because of the time-frame of development of the disease,
      there has been an association with childhood vaccination. Consequently,
      prevailing therapies attempt to address these causes in one, or a combination, of
      three ways: diet restriction (removing casein and gluten); supplementation with
      exogenous enzymes; and probiotic bacteria. Until recently, none of the therapies
      addressed the molecular mechanisms that may be at work in the development and
      progression of autism. This paper presents potential molecular and cellular
      mechanism related to autism as well as discusses their application to the
      treatment of the disease through the application of genomeceuticals.
      Additionally, a link between developmentally associated aberrant immune and
      inflammatory responses, and autism is suggested and explored.

PMID- 11461172
TI  - Modulation of adipocyte lipoprotein lipase expression as a strategy for
      preventing or treating visceral obesity.
AB  - As compared to subcutaneous adipocytes, visceral adipocytes have high basal
      lipolysis, are highly sensitive to catecholamines, and are poorly sensitive to
      insulin; these traits are amplified when visceral adipocytes hypertrophy. As a
      result, enlarged visceral fat stores tend to flood the portal circulation with
      free fatty acids at metabolically inappropriate times when fatty acids are
      unlikely to be oxidized, thus exposing tissues to excessive free fatty acid
      levels and giving rise to the insulin resistance syndrome. A logical approach to
      preventing or correcting visceral obesity is to down-regulate the lipoprotein
      lipase (LPL) activity of visceral adipocytes relative to that expressed in
      subcutaneous adipocytes and skeletal muscle. IGF-I activity appears to be a
      primary determinant of visceral LPL activity in humans; systemic IGF-I activity
      is decreased when diurnal insulin secretion is low, when hepatocytes detect a
      relative paucity of certain essential amino acids, and when estrogens are
      administered orally. The ability of alpha-glucosidase inhibitor therapy to
      selectively reduce visceral adiposity suggests that down-regulation of diurnal
      insulin secretion and/or IGF-I activity may indeed have a greater impact on LPL
      activity in visceral fat than in subcutaneous fat. Thus, low-glycemic-index,
      vegan, high-protein, or hypocaloric diets can be expected to decrease visceral
      LPL activity, as can postmenopausal estrogen therapy. Furthermore, estrogen
      enhances the LPL activity of non-pathogenic gluteofemoral fat cells, whereas
      testosterone decreases visceral LPL activity in men; this may explain why sex
      hormone replacement in middle-aged people of both sexes has a favorable impact on
      visceral fat and insulin sensitivity. Beta-adrenergic activity suppresses
      transcription of LPL in adipocytes; this phenomenon may contribute to the
      favorable impact of exercise training on visceral obesity; conceivably,
      preadministration of safe drugs that boost catecholamine activity (caffeine,
      yohimbine) could potentiate this beneficial effect of exercise. Glucocorticoids
      selectively increase the LPL activity of visceral adipocytes; while there is
      currently no convincing evidence that psychological stress is a major determinant
      of visceral adiposity, or that stress management techniques can help to correct
      visceral obesity, reports that anxiolytic therapy can improve glycemic control in
      type 2 diabetes should encourage further research along these lines.

PMID- 11461173
TI  - A bridge between neuroscience and oncology: prostate cancer genesis. A 'negative'
      consequence of learning?
AB  - Prostate cancer has become the most commonly diagnosed cancer in men over recent
      years. The initiating mechanism for tumorigenesis within the prostate remains an
      unknown. The observation, that the cancer incidence in patients with chronic
      neurological disabilities is significantly lower than in the normal population
      lead to the hypothesis, that changed processing due to a barrage of aberrant
      sensory information within a healthy CNS can trigger events within the prostate
      cell, that cause malignant transformation. There is a broad overlap of cellular
      mechanism of gene expression, that lead to either long term potentiation,
      learning and memory storage or deregulated differentiation and malignant
      transformation.

PMID- 11461174
TI  - A leukocyte and erythrocyte adhesiveness/aggregation test to reveal the presence
      of smoldering inflammation and risk factors for atherosclerosis.
AB  - The number of white blood cells in the peripheral blood, the presence of
      inflammation, increased fibrinogen concentrations and hyperlipidemia are
      established risk factors for atherosclerosis. It is known that
      hyperfibrinogenemia and hyperlipidemia cause increased erythrocyte aggregation,
      that inflammation will confer increased adhesive properties upon white blood
      cells and that the increased number of white blood cells can be detected in the
      peripheral blood. Therefore, we adopted a simple slide test and image analysis to
      determine the number of peripheral blood leukocytes and their state of
      adhesiveness/aggregation together with an erythrocyte adhesiveness/aggregation
      test to reveal the presence of these risk factors. The significant correlation
      between the fibrinogen and cholesterol concentration and the erythrocyte
      aggregation, between the white blood count and the number of leukocytes on the
      slides, and between the concentration of C-reactive protein and leukocyte
      adhesiveness indicate that we have succeeded in designing a simple one-step
      screening test that will identify patients at risk for atherosclerosis.

PMID- 11461175
TI  - Does peripheral neuropathy allow for the clinical expression of tardive
      dyskinesia by unmasking central nervous system changes?
AB  - Tardive dyskinesia (TD) is a severe and troubling complication of long-term
      typical neuroleptic use whose etiology remains obscure. While it is widely
      believed that central nervous system (CNS) dopamine receptor super-sensitivity is
      involved in the pathogenesis of the condition, it is unclear why some patients
      develop TD while others do not. It is proposed that a subclinical peripheral
      motoneuropathy with consequent enlarging of the motor units may act to unmask
      neuroleptic-induced CNS changes allowing for the expression of TD. To investigate
      this hypothesis we examined motor unit size with electrographic examinations in
      14 patients (six with mild TD; eight without and all with psychotic illness).
      There were no differences between the two groups of patients. While the data do
      not appear to support the hypothesis, a larger study with more severely affected
      patients is required to more adequately test the hypothesis.

PMID- 11461176
TI  - Concurrent administration of sustained-release bezafibrate may counteract the
      increased thrombotic risk associated with oral estrogen therapy.
AB  - Although hormone replacement therapy (HRT) can have many favorable effects on
      serum lipids and on vascular endothelium that presumably mediate the decreased
      risk for heart attack and stroke associated with HRT in observational
      epidemiology, oral estrogen also has various pro-coagulant effects: increases in
      serum triglycerides and factor VII activity, decreases in serum antithrombin III
      and protein S. This may explain the increased risk for venous thromboembolism
      observed with HRT and oral contraceptives, as well as the temporary increase in
      coronary risk noted when women with preexisting coronary disease initiate HRT.
      The well-tolerated hypolipidemic agent bezafibrate has anticoagulant actions that
      are diametrically opposed to the procoagulant effects of oral estrogen: namely,
      reductions in serum triglycerides and factor VII activity, and an increase in
      antithrombin III. However, bezafibrate could be expected to complement the
      protective effects of oral estrogen on serum lipids and on serum IGF-I activity.
      Thus, there is reason to believe that concurrent bezafibrate administration would
      minimize any thrombotic risk associated with HRT or oral contraception, while
      amplifying the health benefits of oral estrogen, and would make it more feasible
      to administer these therapies in women at increased vascular risk. These
      predictions require confirmation in controlled clinical studies. Certain natural
      hypolipidemic agents may also have potential as adjuvants to oral estrogen, but
      their effects on hemostasis require further investigation.

PMID- 11461177
TI  - Why hepatocellular carcinoma cells are unlikely to metastasize: is there a role
      for tissue inhibitor of metalloproteinase-1?
AB  - The question 'Why hepatocellular carcinoma cells are unlikely to metastasize
      although they have a high proliferative activity?' is a major point of interest
      from a cancer physiopathological viewpoint. Recent articles about the roles and
      relationships of some cytokines with matrix degrading enzymes and their
      inhibitors in various types of normal tissues and malignancies give rise to
      another question: 'Does tissue inhibitor of metalloproteinase-1 prevent the
      extrahepatic metastasis of hepatocellular carcinoma cells?' On the basis of many
      evidences, it is highly probable that under the effect of a possible inducing
      mechanism of the cytokines interleukin-6, -1 beta and transforming growth factor
      beta, the increase in concentration of tissue inhibitor of metalloproteinase-1 in
      hepatocellular carcinoma cause increased type I collagen accumulation and
      consequent prevention of cellular detachment, which explains why highly
      proliferative malignant hepatocytes have less metastatic ability.

PMID- 11461178
TI  - Activation of signal-transduction mechanisms may underlie the therapeutic effects
      of an applied electric field.
AB  - Successful treatment of various medical complaints with an applied electric field
      has been reported over the years. The identities of the cellular mechanisms that
      are influenced by this type of treatment and facilitate the positive effects,
      remain elusive. A study of many in vitro and in vivo reports revealed that the
      beneficial effects can be attributed to the activation of membrane proteins, and
      specifically proteins involved in signal-transduction mechanisms. Not only may
      the proteins be affected but it is now well established that enhanced
      Ca(2+)influx, observed to follow electric stimulation of cells, also contributes
      to many calcium-dependent cellular processes which can be linked to the
      therapeutic effects discussed in this paper. An hypothesis of the physical
      changes caused by an applied, relatively small (10(3)to 10(4)V m(-1)range),
      electric field with low to moderate frequency (below 150 Hz), is postulated.

PMID- 11461179
TI  - Chronic fatigue syndrome: neurological findings may be related to blood--brain
      barrier permeability.
AB  - Despite volumes of international research, the etiology of chronic fatigue
      syndrome (CFS) remains elusive. There is, however, considerable evidence that CFS
      is a disorder involving the central nervous system (CNS). It is our hypothesis
      that altered permeability of the blood-brain barrier (BBB) may contribute to
      ongoing signs and symptoms found in CFS. To support this hypothesis we have
      examined agents that can increase the blood-brain barrier permeability (BBBP) and
      those that may be involved in CFS. The factors which can compromise the normal
      BBBP in CFS include viruses, cytokines, 5-hydroxytryptamine, peroxynitrite,
      nitric oxide, stress, glutathione depletion, essential fatty acid deficiency, and
      N-methyl-D-aspartate overactivity. It is possible that breakdown of normal BBBP
      leads to CNS cellular dysfunction and disruptions of neuronal transmission in
      CFS. Abnormal changes in BBBP have been linked to a number of disorders involving
      the CNS; based on review of the literature we conclude that the BBB integrity in
      CFS warrants investigation.

PMID- 11461180
TI  - Is there a relationship between tissue inhibitor of metalloproteinase-1 and
      transforming growth factor-beta 1 with respect to malignant melanoma progression?
AB  - Recent articles about the roles and relationships of tissue inhibitor of
      metalloproteinase-1 and transforming growth factor-beta 1 in various types of
      normal tissues and malignancies give rise to the question: 'Is there a
      relationship between them with regard to malignant melanoma progression?' In the
      light of many references, it seems to be highly probable that the tissue
      inhibitor of metalloproteinase-1, -- being a multifunctional protein -- functions
      as a growth factor with possible stimulation by transforming growth factor-beta 1
      in progression of malignant melanoma, rather than its other existing functions in
      many different normal and cancer tissues (e.g. inhibition of the matrix
      metalloproteinases or functioning as an insignificant inhibitor of angiogenesis).

PMID- 11461181
TI  - Self-treatment for gout.
AB  - After describing some of the symptoms of gout and considering some causes, such
      as an excess of ethanol, the source of the pain in the infected joint is
      discussed. This is known to be from urate crystals formed in the synovial fluid
      inside the joint. It is suggested herein that the pain is due to grinding from
      the crystals through the surface film of the joint, and possibly into the bone
      itself, which is relatively soft. The pain then stems in part from the resulting
      inflammation. The key hypothesis is that these urate crystals dissolve on
      warming. Hence, by warming the joint concerned in hot water, and moving the joint
      around to encourage diffusion, the urate concentration is reduced and crystals no
      longer form, provided the treatment is continued.

PMID- 11461182
TI  - Cancer and metaphysics.
AB  - Metaphysics, is generally a pleasant, and harmless intellectual endeavor. Even if
      leading to wrong conclusions, nobody is hurt. Suppose that contrary to general
      belief, the Big Bang (1) never happened and the world is eternal. No harm is
      done. Some philosophers, like Kant, enjoyed life despite the fact that, nature,
      or the thing in itself, eluded their understanding (2). But suppose that the
      thing in itself is your patient, and you apply metaphysical reasoning for his
      treatment, metaphysics may occasionally be damaging. This is particularly
      pertinent to cancer, a disease that is haunted by false metaphysical statements.
      Since cancer is part of medicine, the present discourse deals with medical
      metaphysics. Medicine provides a simple way, or rule of thumb, for distinguishing
      between correct and wrong medical metaphysical statements. If they harm the
      patient, they are wrong, and if they aid him, they are correct. Statements that
      do not affect a patient's well being, e.g., 'Big Bang may be hazardous to your
      health', are of no apparent value and doubtful. Since treatment outcome is
      generally uncertain, the physician continually searches for new ideas that may
      aid his patient, even if they are metaphysical. In diseases, like cancer, that
      elude his understanding, his adherence to metaphysics intensifies, and he is
      ready to consider even doubtful suggestions for treatment. Yet by relaxing the
      rules of thumb for evaluating metaphysical concepts, he gradually slips into the
      irrational domain.

PMID- 11461183
TI  - Theoretical mechanistic basis of the toxic effects and efficacy of
      dideoxycytidine in HIV:AIDS.
AB  - Based on the structure of dideoxycytidine (ddc), the toxic effects of nitroso,
      areneimine, epoxide, hydroxyl free radical (*OH) and calcium chelating propensity
      respectively were evaluated using theoretical mechanistic biochemistry
      techniques. The 4-NH(2)group of the pyrimidine ddc structure was positive (+) for
      nitroso, (+) for areneimine, (+) for *OH; (+) for epoxide and negative (-) for
      calcium chelating propensity TMB toxic effects. The *OH was used to evaluate the
      TMB efficacy of ddc based on the structure of HIV. The *OH was found to be
      capable of damaging each of the following of the HIV structure: (1) the outer
      lipid membrane; (2) the glycoproteins of the envelope; (3) the viral RNA; (4) the
      p18 and p24 proteins in the core of the virus and (5) the reverse transcriptase
      replicating enzyme. The *OH is, therefore, exhibiting the characteristics of a
      'bullet exterminator' for HIV:AIDS by attacking from the outwards inwards.
      Combination therapy of Artesunate (At) + AZT + ddc > At + AZT > AZT + ddc = At +
      ddc in the efficacy of HIV:AIDS was postulated.

PMID- 11461184
TI  - Lactobacilli-mediated control of vaginal cancer through specific reactive oxygen
      species interaction.
AB  - Klebanoff et al. proposed that hydrogen peroxide-producing lactobacilli and
      peroxidase in the vagina of healthy women might be responsible for the prevention
      of vaginosis and also might exert an antitumor effect (1). Based on recent
      evidence on superoxide anion generation by transformed cells (2,3) and on the
      potential of myeloperoxidase for selective apoptosis induction in transformed
      cells (4), a model for specific reactive oxygen species interaction during
      lactobacilli-mediated tumor control in the vagina is presented here. We propose
      that peroxidase, which converts hydrogen peroxide into hypochlorous acid, is
      responsible for creating a microbicidal vaginal milieu by maintaining a balanced,
      non-toxic, steady state level of the microbicides H(2)O(2)and HOCI. In case
      individual superoxide anion-producing transformed cells eventually appear in the
      mucosa they will be driven into apoptosis by interaction of HOCI with superoxide
      anions which leads to the generation of hydroxyl radicals. Hence selective
      apoptosis induction in transformed cells represents the key element of
      lactobacilli-mediated antitumor defense. Since papilloma virus infected cells are
      resistant to this pathway of apoptosis induction, they are plausible candidates
      for circumvention of lactobacilli-mediated control of oncogenesis.

PMID- 11461185
TI  - Upregulation of lymphocyte apoptosis as a strategy for preventing and treating
      autoimmune disorders: a role for whole-food vegan diets, fish oil and dopamine
      agonists.
AB  - Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is
      crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which
      are lymphocyte growth factors, may have the potential to suppress apoptosis in
      thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in
      omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food
      vegan diets may downregulate systemic IGF-I activity, it is proposed that such a
      diet, in conjunction with fish oil supplementation and treatment with dopamine
      agonists capable of suppressing prolactin secretion, may have utility for
      treating and preventing autoimmune disorders. This prediction is consistent with
      the extreme rarity of autoimmune disorders among sub-Saharan black Africans as
      long as they followed their traditional quasi-vegan lifestyles, and with recent
      ecologic studies correlating risks for IDDM and for multiple sclerosis mortality
      with animal product and/or saturated fat consumption. Moreover, there is evidence
      that vegan or quasi-vegan diets are useful in the management of rheumatoid
      arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist
      bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity,
      and there is preliminary evidence that this drug may be clinically useful in
      several human autoimmune diseases; better tolerated D2-specific agonists such as
      cabergoline may prove to be more practical for use in therapy. The moderate
      clinical utility of supplemental fish oil in rheumatoid arthritis and certain
      other autoimmune disorders is documented. It is not unlikely that extra-thymic
      anti-inflammatory effects contribute importantly to the clinical utility of vegan
      diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low
      latitude or high altitude on autoimmune risk may be mediated by superior vitamin
      D status, which is associated with decreased secretion of parathyroid hormone;
      there are theoretical grounds for suspecting that parathyroid hormone may inhibit
      apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may
      be largely responsible for the relative protection from autoimmunity enjoyed by
      men, and merit further evaluation for the management of autoimmunity in women. It
      will probably prove more practical to prevent autoimmune disorders than to
      reverse them once established; a whole-food vegan diet, coupled with fish oil and
      vitamin D supplementation, may represent a practical strategy for achieving this
      prevention, while concurrently lowering risk for many other life-threatening
      'Western' diseases.

PMID- 11461186
TI  - Mucolipidosis type IV.
AB  - Mucolipidosis type IV (MLIV) is a neurodegenerative lysosomal storage disorder
      characterized by psychomotor retardation and ophthalmological abnormalities,
      including corneal opacities, retinal degeneration, and strabismus. Severely
      affected as well as milder patients have been described. Over 80% of the MLIV
      patients are Ashkenazi Jews; the estimated heterozygote frequency in this
      population is 1/100. The disease is classified as a mucolipidosis due to the
      simultaneous lysosomal storage of lipids together with water-soluble substances.
      A broad spectrum of lipids and acid mucopolysaccharides were identified as the
      storage substances. Kinetic studies demonstrated that this heterogeneous storage
      stems from an abnormal endocytosis process in cells from MLIV patients of
      membrane components from late endosomes to the lysosomes and/or delayed efflux to
      the Golgi apparatus. The MLIV gene was mapped to chromosome 19p13.2--13.3 where a
      novel gene, MCOLN1, with MLIV-causing mutations, was identified. Two mutations
      were found among 95% of the Ashkenazi MLIV alleles, including an intronic
      acceptor splice-site mutation in 72% of the alleles and a partial gene deletion
      in 23%. Each of these mutations was associated with a defined haplotype in this
      chromosomal region. Other mutations were mostly identified in single, Ashkenazi
      and non-Ashkanazi patients, including missense, nonsense nucleotide deletions,
      and insertions. All mutations but one were identified in patients exhibiting the
      severe phenotype, an in-frame amino acid deletion was identified in a mild
      patient. MCOLN1 encodes a 580 aa protein, mucolipin 1, which is a member of a new
      protein family of unknown function at present, the mucolipins. Mucolipin 1 is a
      membrane protein with 6 transmembrane domains, a serine lipase, and nuclear
      localization signal motives. The protein shows homology to a group of calcium
      channels of the TRP/TRPL family. The involvement of this protein in the
      endocytosis process of membrane components is currently studied. A population
      screening operation among the Ashkenazi population for the detection of
      heterozygotes has been started in Israel as a prevention program.

PMID- 11461187
TI  - The LEP gene and age of menarche: maternal age as a potential cause of hidden
      stratification in association studies.
AB  - Leptin has a powerful effect on fertility and the initiation of puberty in
      addition to its effect on obesity. It has been suggested that that in times of
      fasting, infertility induced by low leptin levels protect the female from the
      energy demands of pregnancy. Despite this there have been no studies of the
      potential role of LEP gene variants on the age of onset of menarche. We genotyped
      183 non-Hispanic Caucasian adult females at the LEP D7S1875 dinucleotide repeat
      polymorphism. The alleles were placed into three genotypes, <208/<208 bp,
      heterozygotes, and > or =208/> or =208 bp. A hierarchical ANOVA was performed
      with age of menarche as the dependent variable and LEP(1875) genotypes and
      maternal age (age of the mothers at birth of the subject) as independent
      variables. There was a significant (P </= 0.006) interaction of LEP(1875) x
      maternal age but neither independent variable was significant by itself. This was
      due to an "association crossover effect" in which the LEP(1875) by age of
      menarche effects were in opposite directions for those with a maternal age of <30
      years compared to those with a maternal age of > or =30 years. If maternal age
      effects prove to be generalized, failure to take them into consideration could
      provide a source of hidden stratification that could significantly alter the
      replication of association studies.

PMID- 11461188
TI  - Generation of a mouse with low galactocerebrosidase activity by gene targeting: a
      new model of globoid cell leukodystrophy (Krabbe disease).
AB  - Globoid cell leukodystrophy (Krabbe disease) is a severe leukodystrophy caused by
      mutations in the galactocerebrosidase (GALC) gene leading to extremely low (less
      than 5% of normal activity) GALC activity. Human patients include primarily
      severely affected infants as well as patients with a later onset of symptoms. The
      infants usually die before 2 years of age, but it is difficult to predict the
      clinical course in older patients. In addition to these patients, additional
      individuals identified in this laboratory have 10--20% of normal GALC activity
      measured in accessible tissues. These individuals have a wide range of clinical
      presentations involving neurological degeneration. On molecular analysis of the
      GALC gene they all have three or more mutations considered to be normal
      polymorphisms resulting in amino acid changes in the two copies of the GALC gene.
      In order to investigate the role these amino acid changes may play on clinical,
      biochemical, and pathological findings, a new transgenic mouse was generated by
      homologous recombination. After preliminary studies determined what effect each
      amino acid change had on mouse GALC activity in transient transfection
      experiments, mice containing a cysteine residue at codon 168 instead of histidine
      (H168C) were produced. These mice developed symptoms, but they were delayed by 10
      -15 days from the well-characterized twitcher (twi) mouse. They accumulated
      psychosine slightly slower than twi mice, showed pathological changes less severe
      than twi mice in the central and peripheral nervous systems, and live about 15
      days longer than twi mice. They have large litters and will play a role in
      therapy trials using new procedures currently under development.

PMID- 11461189
TI  - In vivo variability of TMA oxidation is partially mediated by polymorphisms of
      the FMO3 gene.
AB  - Trimethylaminuria (TMAU) results from an accumulation of an excessive amount of
      unoxidized trimethylamine that is excreted in urine and body secretions.
      Mutations of the flavin-containing monooxygenase 3 (FMO3) gene (a hepatic phase I
      drug-metabolizing enzyme) account for the severe recessively encoded form of this
      condition. We have previously described a number of FMO3 polymorphisms which in
      vitro exhibit reduced substrate affinity for several FMO substrates. Here we show
      that three prevalent polymorphisms (E158K, V257M, and E308G) inherited in
      particular combinations confer a slight decrease in TMA oxidation under normal
      physiological conditions, which may be clinically "silent." With the use of
      substrate loading or with the interaction of other known modulators of FMO3
      activity such as hormonal influences, these genotypes may predispose to mild
      TMAU.

PMID- 11461190
TI  - Homomeric and heteromeric interactions between wild-type and mutant phenylalanine
      hydroxylase subunits: evaluation of two-hybrid approaches for functional analysis
      of mutations causing hyperphenylalaninemia.
AB  - Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase
      gene (PAH), while mutations in genes encoding the two enzymes (dihydropteridine
      reductase, DHPR, and pterin-4-alpha-carbinolamine dehydratase, PCD) required for
      recycling of its cofactor, tetrahydrobiopterin (BH(4)), cause other rarer disease
      forms of hyperphenylalaninemia. We have applied a yeast two-hybrid method, in
      which protein--protein interactions are measured by four reporter gene
      constructs, to the analysis of six PKU-associated PAH missense mutations (F39L,
      K42I, L48S, I65T, A104D, and R157N). By studying homomeric interactions between
      mutant PAH subunits, we show that this system is capable of detecting quite
      subtle aberrations in PAH oligomerization caused by missense mutations and that
      the observed results generally correlate with the severity of the mutation as
      determined by other expression systems. The mutant PAH subunits are also shown in
      this system to be able to interact with wild-type PAH subunits, pointing to an
      explanation for apparent dominant negative effects previously observed in
      obligate heterozygotes for PKU mutations. Based on our findings, the applications
      and limitations of two-hybrid approaches in understanding mechanisms by which PAH
      missense mutations exert their pathogenic effects are discussed. We have also
      used this technique to demonstrate homomeric interactions between wild-type DHPR
      subunits and between wild-type PCD subunits. These data provide a basis for
      functional studies on HPA-associated mutations affecting these enzymes.

PMID- 11461191
TI  - Feature (gene) selection in gene expression-based tumor classification.
AB  - There is increasing interest in changing the emphasis of tumor classification
      from morphologic to molecular. Gene expression profiles may offer more
      information than morphology and provide an alternative to morphology-based tumor
      classification systems. Gene selection involves a search for gene subsets that
      are able to discriminate tumor tissue from normal tissue, and may have either
      clear biological interpretation or some implication in the molecular mechanism of
      the tumorigenesis. Gene selection is a fundamental issue in gene expression-based
      tumor classification. In the formation of a discriminant rule, the number of
      genes is large relative to the number of tissue samples. Too many genes can harm
      the performance of the tumor classification system and increase the cost as well.
      In this report, we discuss criteria and illustrate techniques for reducing the
      number of genes and selecting an optimal (or near optimal) subset of genes from
      an initial set of genes for tumor classification. The practical advantages of
      gene selection over other methods of reducing the dimensionality (e.g., principal
      components), include its simplicity, future cost savings, and higher likelihood
      of being adopted in a clinical setting. We analyze the expression profiles of
      2000 genes in 22 normal and 40 colon tumor tissues, 5776 sequences in 14 human
      mammary epithelial cells and 13 breast tumors, and 6817 genes in 47 acute
      lymphoblastic leukemia and 25 acute myeloid leukemia samples. Through these three
      examples, we show that using 2 or 3 genes can achieve more than 90% accuracy of
      classification. This result implies that after initial investigation of tumor
      classification using microarrays, a small number of selected genes may be used as
      biomarkers for tumor classification, or may have some relevance in tumor
      development and serve as a potential drug target. In this report we also show
      that stepwise Fisher's linear discriminant function is a practicable method for
      gene expression-based tumor classification.

PMID- 11461192
TI  - Reversal of type 2 diabetes in mice by products of malaria parasites. II. Role of
      inositol phosphoglycans (IPGs).
AB  - We have previously shown that infection with Plasmodium yoelii malaria or
      injection of extracts from malaria-parasitized red cells induces hypoglycemia in
      normal mice and normalizes the hyperglycemia in mice made moderately diabetic
      with streptozotocin. Inositol phosphoglycans (IPGs) are released outside cells by
      hydrolysis of membrane-bound glycosylphosphatidylinositols (GPIs), and act as
      second messengers mediating insulin action. The C57BL/Ks-db/db and C57BL/6J-ob/ob
      mice offer good models for studies on human obesity and Type 2 diabetes. In the
      present study, we show that a single iv injection of IPG-A or IPG-P extracted
      from P. yoelii significantly (P < 0.02) lowers the blood glucose in STZ-diabetic,
      db/db, and in ob/ob mice for at least 4--6 h. Using rat white adipocytes, IPG-P
      increased lipogenesis by 20--30% in the presence and absence of maximal
      concentrations of insulin (10(-8) M) (P < 0.01) and stimulated pyruvate
      dehydrogenase (PDH) phosphatase in a dose-related manner. Both IPG-A and IPG-P
      inhibited c-AMP-dependent protein kinase (PKA) in a dose-related manner.
      Compositional analysis of IPGs after 24 h hydrolysis revealed the presence of myo
      inositol, phosphorus, galactosamine, glucosamine, and glucose in both IPG-A and
      IPG-P. However, hydrolysis of IPGs for 4 h highlighted differences between IPG-A
      and IPG-P. There are some functional similarities between P. yoelii IPGs and
      those previously described for mammalian liver. However, this is the first report
      of the hypoglycemic effect of IPGs in murine models of Type 2 diabetes. We
      suggest that IPGs isolated from P. yoelii, when fully characterized, may provide
      structural information for the synthesis of new drugs for the management of
      diabetes mellitus.

PMID- 11461193
TI  - Impairment of type III group B Streptococcus-stimulated superoxide production and
      opsonophagocytosis by neutrophils in diabetes.
AB  - The effect of hyperglycemia upon susceptibility to bacterial infection in
      diabetes mellitus is incompletely elucidated. The present experiments assessed
      the effect of hyperglycemia upon neutrophil-mediated phagocytosis of type III
      group B Streptococcus (GBS). Type III GBS was chosen for study because the
      incidence of invasive GBS disease is substantially increased in type 2 diabetic
      compared with nondiabetic subjects. The hypothesis tested was that severe
      hyperglycemia would alter neutrophil metabolism by diverting NADPH from
      superoxide production into the aldose reductase-dependent polyol pathway that
      converts glucose into sorbitol and thus would impair opsonophagocytosis (OP) of
      type III GBS. Neutrophils from 10 adults with type 2 diabetes had no intrinsic
      phagocytic defect under baseline glycemic conditions. After equilibration in 60
      or 120 mM glucose or in 60 mM choline chloride, OP activity was reduced
      significantly (P < or = 0.03). Neutrophil superoxide production correlated with
      glucose concentration and also was significantly reduced during hyperglycemia (P
      < 0.05). Addition of III GBS capsular polysaccharide-specific IgG in a sufficient
      concentration supported efficient OP, even during hyperglycemia. Alrestatin, an
      aldose reductase inhibitor, increased superoxide production and significantly
      improved OP of type III GBS (P = 0.03). Thus, diversion of NADPH into the polyol
      pathway is one mechanism by which OP of GBS III is impaired during hyperglycemia,
      and this effect is mitigated when levels of capsular polysaccharide-specific IgG
      are sufficient.

PMID- 11461194
TI  - 3-Hydroxy-3-methylglutaric aciduria in an Italian patient is caused by a new
      nonsense mutation in the HMGCL gene.
AB  - 3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive inborn error of
      metabolism caused by deficiency of the mitochondrial enzyme 3-hydroxy-3
      methylglutaryl-CoA lyase (HMGCL). Up to now only a few mutations have been
      reported in the HMGCL gene. We report the first Italian patient, a female who
      presented metabolic acidosis at 3 days of age and then 3 months later. Analysis
      of urinary organic acids showed the excretion of 3-hydroxy-3-methylglutaric acid,
      3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid. A
      defect of HMGCL activity was suspected and then confirmed on cultured skin
      fibroblasts. Brain RM showed a diffuse mild abnormality of cerebral white matter
      in the periventricular regions, and the single voxel proton MRI spectroscopy
      showed abnormal peaks. In the patient's full-length HMGCL-cDNA a new c286C > T
      transition that leads to the stop codon Q96X was detected at the homozygous
      level. This mutation, that gives rise to a truncated protein, was confirmed in
      the patient's and also her parents' genomic DNA. The severe genetic lesion
      identified in the patient, which is in contrast with the mild clinical phenotype,
      stresses the importance of early diagnosis and therapy in HMGCL deficiency.

PMID- 11461195
TI  - Impaired mitochondrial fatty acid oxidative flux in fibroblasts from a patient
      with malonyl-CoA decarboxylase deficiency.
AB  - Malonyl-CoA decarboxylase deficiency is a rare inborn error of metabolism. It has
      been suggested but never demonstrated that many of the clinical features arise
      due to inhibition of mitochondrial fatty acid oxidation by accumulated malonyl
      CoA. We studied the oxidation of fatty acids in cultured skin fibroblasts from a
      recently described patient with malonyl-CoA decarboxylase deficiency. There was a
      marked reduction in the oxidation of palmitic and myristic acids both under
      baseline conditions and when the cells were cultured in the presence of high
      concentrations of acetate, a malonyl-CoA precursor. These results suggest that
      there is inhibition of fatty acid oxidation in malonyl-CoA decarboxylase
      deficiency and that this inhibition may be related to some of the clinical
      phenotypes.

PMID- 11461196
TI  - A phenylalanine hydroxylase amino acid polymorphism with implications for
      molecular diagnostics.
AB  - Mutations in the gene encoding phenylalanine hydroxylase (PAH, EC 1.14.16.1) are
      associated with various degrees of hyperphenylalaninemia, including classical
      phenylketonuria (PKU). We examined the PAH gene in a Brazilian PKU family of
      African origin and identified three missense variants, R252W (c.754C --> T),
      K274E (c.820A --> G), and I318T (c.953T --> C), the two latter of which were
      transmitted in cis. Expression analyses in two different in vitro systems showed
      that I318T is associated with profoundly decreased enzyme activity, whereas the
      enzyme activity of K274E is indistinguishable from that of the wild-type protein.
      Detailed kinetic analyses of PAH expressed in E. coli showed that the K274E
      mutant protein has kinetic properties similar to that of the wild-type protein.
      Population studies have suggested that the K274E variant occurs on approximately
      4% of African-American PAH alleles, whereas the neonatal screening incidence of
      PKU among African Americans is only 1:100,000. This is to our knowledge the first
      demonstration of a PAH missense variant with no apparent association to PAH
      deficiency. Awareness of this common variant may be helpful to laboratories that
      perform molecular diagnosis of PAH deficiency in populations of African origin.

PMID- 11461197
TI  - Genetic polymorphism (G80A) of reduced folate carrier gene in ethnic populations.

PMID- 11461198
TI  - Primacy Effects in Justice Judgments: Testing Predictions from Fairness Heuristic
      Theory.
AB  - We tested predictions from fairness heuristic theory that justice judgments are
      more sensitive to early fairness-relevant information than to later fairness
      relevant information and that this primacy effect is more evident when group
      identification is higher. Participants working on a series of three tasks
      experienced resource failures that interfered with their productivity and always
      had the possibility of explaining problems to a supervisor. In a manipulation of
      the timing of fairness-relevant experiences, the supervisor refused to consider
      explanations on the first, second, or third of three work trials (but did
      consider explanations on the other two trials) or the supervisor never refused to
      hear the explanations. Prior to the work periods, the participants either had or
      had not undergone a manipulation designed to induce greater identification with
      the work group. As predicted, the timing of fairness-relevant experiences showed
      a primacy effect on fairness judgments and acceptance of authority in the high
      identification conditions and no evidence of such an effect in the low
      identification conditions. The implications of the findings for understanding the
      psychology of justice and for real-world justice phenomena are discussed.
      Copyright 2001 Academic Press. 

PMID- 11461199
TI  - Predicting Affective Responses to Unexpected Outcomes.
AB  - In decisions under uncertainty, decision makers confront two uncertainties: the
      uncertain linkage between actions and outcomes and the uncertain linkage between
      these outcomes and his or her affective responses to them. The two studies
      reported here examine affective responses to expected and unexpected outcomes in
      various settings. In Study 1, a scenario-based laboratory experiment (N = 149),
      we examined subjects' predicted responses to a range of outcomes, as a function
      of how surprising the outcome was. Study 2, a field study (N = 127), involved the
      expectations of bowlers about their scores in an upcoming game and about their
      responses to various outcomes at, above, and below expectations. We also measured
      actual affective reactions after the bowlers had completed their games. Findings
      suggest that subjects both expect and experience a loss-averse, expectation-based
      value function broadly of the Prospect Theory type. They also anticipate, and
      experience, an amplifying effect of outcome surprise, though they underestimate
      its size. We argue that such underestimation, together with overtight prediction
      ranges, may expose subjects to much larger affective variation with outcome
      variability than they anticipate. Copyright 2001 Academic Press. 

PMID- 11461200
TI  - Does Time Constraint on Users Negate the Efficacy of Decision Support Systems?
AB  - Time constraint can impair decision performance: time-constrained decision makers
      process information faster, process less information, and use less rigorous
      decision strategies. On the other hand, properly designed decision support
      systems (DSSs) can induce decision makers to process more information and use
      more rigorous decision strategies, which can result in enhanced performance. In
      this study, we investigate, drawing on bounded rationality and cost-benefit
      theories of DSS use, whether these salutary effects of DSSs still hold in time
      constrained environments. Our experimental results replicate past research
      regarding the effects of time constraint and DSSs taken separately and also show
      that the positive effects of DSSs are maintained when decision makers are under
      time constraint. That is, consistent with hypotheses, time-constrained
      participants processed information in a more compensatorylike manner when aided
      by DSSs than when not. Some of the results suggest that the negative effects of
      time constraint can be mitigated or even eliminated by the use of DSSs, but some
      participants did not take full advantage of the DSS to combat time constraint.
      Copyright 2001 Academic Press. 

PMID- 11461201
TI  - The Disjunction Effect: Does It Exist for Two-Step Gambles?
AB  - One of the basic axioms of the rational theory of decision under uncertainty is
      Savage's (1954) Sure Thing Principle. It states that if Prospect x is preferred
      to Prospect y knowing that Event A occurred, and if x is preferred to y knowing
      that A did not occur, then x should also be preferred to y when it is not known
      whether A occurred. Tversky and Shafir (1992) claim to have demonstrated a
      violation of this principle in two-step gambles, which is termed a disjunction
      effect. The present article evaluates the replicability of the disjunction effect
      for two-step gambles. The findings show that people do not violate the sure thing
      principle in repeated gambles. The validity of alleged violations in other
      paradigms is discussed. Copyright 2001 Academic Press. 

PMID- 11461202
TI  - Calibration of Subjective Probability Judgments in a Naturalistic Setting.
AB  - Results of previous calibration studies are used to identify features of the
      decision maker and the decision environment which might be expected to result in
      good calibration. Racetrack bettors and, in particular, the UK parimutuel betting
      market are identified as possessing such characteristics. In order to explore
      calibration in this setting, an analysis is undertaken of bets placed on 19,396
      horses. A close correlation is observed between the subjective probability
      judgments of horses' success, implicit in the bettors' wagering activities, and
      the objective probability of success of the horses concerned. Explanations for
      the results are offered in terms of characteristics of racetrack bettors and the
      naturalistic setting, with particular reference to the operation of the betting
      market. The results contribute to an emergent school of thought which advocates
      naturalistic enquiry as a complement to laboratory-based experiments in further
      developing the understanding of decision making. Copyright 2001 Academic Press. 

PMID- 11461203
TI  - Do Conditional Hypotheses Target Rare Events?
AB  - When testing hypotheses, rare or unexpected observations are normatively more
      informative than common observations, and recent studies have shown that
      participants' behavior reflects this principle. Research has also shown that,
      when asked to test conditional hypotheses ("If X, then Y") that are abstract or
      unfamiliar, participants overwhelmingly consider a supporting observation
      mentioned in the hypothesis (X&Y) to be more informative than a supporting
      observation not mentioned ( approximately X approximately Y). These two empirical
      findings would mesh well if conditional hypotheses tend to be phrased in terms of
      rare, rather than common, events. Six experiments are reported indicating that
      people do have a tendency-often a very strong one-to phrase conditional
      hypotheses in terms of rare events. Thus, observations mentioned in conditional
      hypotheses might generally be considered highly informative because they usually
      are highly informative. Copyright 2001 Academic Press. 

PMID- 11461204
TI  - Cognitive Diversity and Consensus in Group Decision Making: The Role of Inputs,
      Processes, and Outcomes.
AB  - This study contributes to the new and growing body of research on shared
      cognition by examining how individuals entering a group decision-making context
      with different perspectives of the issues to be discussed arrive at cognitive
      consensus. Cognitive consensus refers to similarity among group members regarding
      how key matters are conceptualized and was operationalized as shared assumptions
      underlying decision issues in the present research. Utilizing 37 student groups
      participating in a multi-issue decision-making exercise, the study investigated
      antecedents and correlates of cognitive consensus. Results revealed that
      unanimity decision rule groups achieved more cognitive consensus than majority
      rule groups. In addition, group members inquiring concerning the reasons
      underlying others' decision preferences, accepting others' viewpoints as
      legitimate, and incorporating others' perspectives into their own interpretations
      of the issues was positively related to arriving at a greater degree of cognitive
      consensus. Cognitive consensus also positively influenced expectations regarding
      decision implementation and satisfaction. Copyright 2001 Academic Press. 

PMID- 11461205
TI  - Content Effects on Decision Making.
AB  - How does the domain or subject matter of a decision problem affect the outcome of
      the decision? Although decision-making research typically dismisses content as
      merely a cover story, the present research shows that it plays a fundamental role
      in the decision process by influencing the information processing that underlies
      it. An experiment is reported in which the same basic decision problem was
      presented in several content domains (legal traffic tickets, academic course
      grades, stock investments, and casino gambling). The changes in content led to
      changes in both strategies and mental representations, which in turn led to
      changes in decision outcomes, even though measures of the subjective utilities of
      the options remained unchanged. Copyright 2001 Academic Press. 

PMID- 11461206
TI  - Managing Workplace Conflict in the United States and Hong Kong.
AB  - We propose that managers have norms (standards of appropriate behavior) for
      resolving conflict, that these norms are culturally based, and that they explain
      cultural differences in conflict management outcomes. We confirm that the
      traditionally American norms of discussing parties' interests and synthesizing
      multiple issues were exhibited more strongly by American managers than by their
      Hong Kong Chinese counterparts. In addition, we confirm that the traditionally
      Chinese norms of concern for collective interests and concern for authority
      appeared more strongly among Hong Kong Chinese managers than among their American
      counterparts. American managers were more likely than Hong Kong Chinese managers,
      to resolve a greater number of issues and reach more integrative outcomes, while
      Hong Kong Chinese managers were more likely to involve higher management in
      conflict resolution. Culture had a significant effect on whether parties selected
      an integrative outcome rather than an outcome that involved distribution,
      compromise, higher management, or no resolution at all. Conflict norms explained
      the cultural differences that existed between reaching an integrative outcome and
      reaching an outcome involving distribution, compromise, or higher management;
      however, conflict norms did not fully explain the cultural differences that
      existed between reaching an integrative outcome and reaching no resolution.
      Copyright 2001 Academic Press. 

PMID- 11461207
TI  - Attribute Framing and Goal Framing Effects in Health Decisions.
AB  - Levin, Schneider, and Gaeth (LSG, 1998) have distinguished among three types of
      framing-risky choice, attribute, and goal framing-to reconcile conflicting
      findings in the literature. In the research reported here, we focus on attribute
      and goal framing. LSG propose that positive frames should be more effective than
      negative frames in the context of attribute framing, and negative frames should
      be more effective than positive frames in the context of goal framing. We test
      this framework by manipulating frame valence (positive vs negative) and frame
      type (attribute vs goal) in a unified context with common procedures. We also
      argue that the nature of effects in a goal-framing context may depend on the
      extent to which the research topic has "intrinsic self-relevance" to the
      population. In the context of medical decision making, we operationalize low
      intrinsic self-relevance by using student subjects and high intrinsic self
      relevance by using patients. As expected, we find complete support for the LSG
      framework under low intrinsic self-relevance and modified support for the LSG
      framework under high intrinsic self-relevance. Overall, our research appears to
      confirm and extend the LSG framework. Copyright 2001 Academic Press. 

PMID- 11461208
TI  - Phase separation in star-polymer-colloid mixtures.
AB  - We examine the demixing transition in star-polymer-colloid mixtures for star arm
      numbers f=2,6,16,32 and different star-polymer-colloid size ratios 0.18< or =q<
      or =0.50. Theoretically, we solve the thermodynamically self-consistent Rogers
      Young integral equations for binary mixtures using three effective pair
      potentials obtained from direct molecular computer simulations. The numerical
      results show a spinodal instability. The demixing binodals are approximately
      calculated and found to be consistent with experimental observations.

PMID- 11461209
TI  - Relationship between dynamical and equilibrium characteristics of glass-forming
      polymeric liquids.
AB  - A connection between measurable equilibrium thermodynamic quantities and a
      nonequilibrium property of supercooled polymeric liquids, namely, the fragility
      index, is proposed within the framework of a synthesis of generalized
      configurational entropy models. The theoretical predictions are compared with
      experimental data on five glass-forming polymers.

PMID- 11461210
TI  - Discontinuous elongation of nematic gels by a magnetic field.
AB  - The effects of a magnetic field on the swelling of a nematic gel immersed in a
      low molecular weight liquid crystal solvent are examined by using a mean field
      theory. The nematic-isotropic (paranematic) phase transition temperature of the
      gel and the solvent is controlled by the external field. As a result of an
      anisotropic coupling between the gel and solvent, the shape of the gel is
      discontinuously (or continuously) elongated with increasing the strength of the
      external field. We examine the condition for a first- and second-order volume
      phase transition of the gel under a magnetic field.

PMID- 11461211
TI  - Surface ordering above the isotropic-smectic-A transition at a silane-treated
      substrate.
AB  - Surface ordering in a homologous series of alkyl cyanobiphenyl (nCB) liquid
      crystals having a direct isotropic-smectic-A (I-A) transition was investigated
      using evanescent-wave ellipsometry. The liquid crystal was bounded by a solid
      substrate treated with a silane surfactant which induced homeotropic
      (perpendicular) ordering of the liquid crystal molecules in the smectic-A phase.
      In the isotropic phase, one of the liquid crystals (10CB) partially wet the
      interface with an orientationally ordered, homeotropically aligned layer. The
      ordered interfacial layer grew without layering transitions but remained finite
      in thickness as the bulk I-A transition was approached. The interfacial layer has
      significantly lower orientational order than is observed in the smectic phase,
      indicating the possibility that the surface region of 10CB may be in a surface
      induced, nonspontaneous nematic phase. The other liquid crystals (11 and 12CB)
      showed no surface ordering behavior whatsoever. Models describing the ordered
      surface layer of 10CB are presented. The results can be interpreted as a sharp
      transition in the surface ordering behavior as the chain length of the liquid
      crystal is varied, at the I-A transition of a liquid crystal.

PMID- 11461212
TI  - Influence of the molecular tilt on the structure of smectic blue phases.
AB  - Smectic blue phases (BP(sm)) are original physical systems of thermotropic liquid
      crystals, displaying a double geometrical frustration: the extension of chirality
      in the three spatial dimensions, such as classical blue phases, and the
      competition between smectic order and helical twist, such as twist grain boundary
      (TGB) phases. We report experimental evidence of the influence of the underlying
      TGB((A) or (C)) phase on the BP(sm) structure.

PMID- 11461213
TI  - Structural properties of the ferrielectric phases of a chiral liquid crystal
      revealed by dynamic light scattering.
AB  - Dynamic light scattering is used to study the antiferro- and ferrielectric phases
      in a bulk sample of the chiral liquid crystal R-10OTBBB1M7. Comparison of the
      detected fluctuation modes in the two ferriphases to calculated selection rules
      for their coupling to light are consistent with the distorted clock structures
      recently reported by an optical ellipsometry study, but indicate that the
      distortion has a polar component in both ferriphases. We also find a surprisingly
      large amplitude and dispersion associated with scattering from fluctuations in
      the tilt angle magnitude. In terms of the discrete interlayer interaction models
      currently being used to account for the ferriphases, this finding suggests that
      the interlayer interaction coefficients are of comparable magnitude to the
      intralayer coefficients that stabilize the tilt angle.

PMID- 11461214
TI  - Crossover behavior for long reptating polymers.
AB  - The Rubinstein-Duke model for polymer reptation is analyzed by means of density
      matrix renormalization techniques. It is found that the crossover in the scaling
      behavior of polymer renewal time (or viscosity) arises from the competing effect
      of the contribution due to tube length fluctuations and higher-order corrections,
      which are of opposite sign. Experiments which ought to emphasize both
      contributions are suggested. The exponent describing the subleading scaling
      behavior of the diffusion coefficient is also investigated.

PMID- 11461215
TI  - Block copolymer micelle coronas as quasi-two-dimensional dilute or semidilute
      polymer solutions.
AB  - Chain-chain interactions in a corona of polymers tethered to a spherical core
      under good solvent conditions are studied using Monte Carlo simulations. The
      total scattering function of the corona as well as different partial
      contributions are sampled. By combining the different contributions in a self
      consistent approach, it is demonstrated that the corona can be regarded as a
      quasi-two-dimensional polymer solution, with a concentration dependence analogous
      to that of an ordinary polymer solution. Scattering due to the corona profile and
      density fluctuation correlations are separated in this approach. The osmotic
      compressibility is extracted from the latter, and it is shown to be a universal
      function of surface coverage, with some deviations at high coverage due to
      surface curvature effects.

PMID- 11461216
TI  - Interfacial and topological measurements of bicontinuous polymer morphologies.
AB  - Bicontinuous morphologies are ubiquitous in nature and occur at various length
      scales. Topological features of two such morphologies arising in an ordered block
      copolymer at equilibrium and a polymer blend during spinodal decomposition are
      measured from three-dimensional images. Interfacial curvature, coordination
      number, and interjunction distance distributions exhibit remarkable similarity in
      these systems, despite vastly different length scales. A channel coordination of
      3 is dominant in both morphologies, and topological measurements such as the
      Euler-Poincare characteristic and genus are reported.

PMID- 11461217
TI  - Composite membrane deformation on the mesoscopic length scale.
AB  - The physics of soft materials can be investigated using nuclear spin-lattice
      relaxation, which depends on the spectral densities of motion in the MHz range.
      For the first time, NMR relaxation has been used to study influences of the acyl
      length, polar head groups, a cosurfactant, and cholesterol on the viscoelastic
      properties of membrane lipids. The results imply the concept of elastic
      deformation is relevant on lengths approximately equal to the bilayer thickness
      and less, involving a broad spectrum of collective modes which contribute to the
      forces between lipid bilayers.

PMID- 11461218
TI  - Estimating Lyapunov exponents in biomedical time series.
AB  - Among nonlinear dynamical invariants, determination of the largest Lyapunov
      exponent is well suited to positive identification of chaos in observed time
      series. When analyzing the dynamics of biomedical series, such as an electro
      encephalogram (EEG), model-based methods should be used. Moreover, in the absence
      of any well founded theoretical model, and because of unexplained variability in
      the data, candidate models must provide for a stochastic component. Here we use
      nonlinear autoregressive stochastic modeling to estimate the dominant Lyapunov
      exponent in an EEG series and compute confidence intervals from surrogate data.
      The results are found to differ from those of approaches which aim at deleting
      noise prior to analysis.

PMID- 11461219
TI  - Solvable multispecies reaction-diffusion processes.
AB  - A family of one-dimensional multispecies reaction-diffusion processes on a
      lattice is introduced. It is shown that these processes are exactly solvable,
      provided a nonspectral matrix equation is satisfied. Some general remarks on the
      solutions to this equation, and some special solutions are given. The large-time
      behavior of the conditional probabilities of such systems is also investigated.

PMID- 11461220
TI  - Directed particle diffusion under "burnt bridges" conditions.
AB  - We study random walks on a one-dimensional lattice that contains weak
      connections, so-called "bridges." Each time the walker crosses the bridge from
      the left or attempts to cross it from the right, the bridge may be destroyed with
      probability p; this restricts the particle's motion and directs it. Our model,
      which incorporates asymmetric aspects in an otherwise symmetric hopping
      mechanism, is very akin to "Brownian ratchets" and to front propagation in
      autocatalytic A+B-->2A reactions. The analysis of the model and Monte Carlo
      simulations show that for large p the velocity of the directed motion is
      extremely sensitive to the distribution of bridges, whereas for small p the
      velocity can be understood based on a mean-field analysis. The single-particle
      model advanced by us here allows an almost quantitative understanding of the
      front's position in the A+B-->2A many-particle reaction.

PMID- 11461221
TI  - Sticky spheres, entropy barriers, and nonequilibrium phase transitions.
AB  - A sticky spheres model to describe slow dynamics of a nonequilibrium system is
      proposed. The dynamical slowing down is due to the presence of entropy barriers.
      An exact steady state analysis of the representative mean field equations, in the
      case when the clusters are chosen with the same a priori probability,
      demonstrates a nonequilibrium phase transition from an exponential cluster size
      distribution to a power law.

PMID- 11461222
TI  - Specific heat of multifractal energy spectra.
AB  - Motivated by the self-similar character of energy spectra demonstrated for
      quasicrystals, we investigate the case of multifractal energy spectra, and
      compute the specific heat associated with simple archetypal forms of multifractal
      sets as generated by iterated maps. We considered the logistic map and the circle
      map at their threshold to chaos. Both examples show nontrivial structures
      associated with the scaling properties of their respective chaotic attractors.
      The specific heat displays generically log-periodic oscillations around a value
      that characterizes a single exponent, the "fractal dimension," of the
      distribution of energy levels close to the minimum value set to 0. It is shown
      that when the fractal dimension and the frequency of log oscillations of the
      density of states are large, the amplitude of the resulting log oscillation in
      the specific heat becomes much smaller than the log-periodic oscillation measured
      on the density of states.

PMID- 11461223
TI  - Speed of reaction-transport processes.
AB  - We present an approach to determining the speed of wave-front solutions to
      reaction-transport processes. This method is more accurate than previous ones.
      This is explicitly shown for several cases of practical interest: (i) the
      anomalous diffusion reaction, (ii) reaction diffusion in an advective field, and
      (iii) time-delayed reaction diffusion. There is good agreement with the results
      of numerical simulations.

PMID- 11461224
TI  - Spatially periodic stochastic system with infinite globally coupled oscillators.
AB  - In this paper we study a spatially periodic stochastic system with infinite
      globally coupled oscillators driven by a constant force F. With two typical
      models we show that when F=0 there is a nonequilibrium transition between the
      state with zero mean field (s=0) and the state with nonzero mean field (s not
      equal 0). For model I, the transition is not a phase transition, while for the
      model II it is (second order). In addition, we find that for coupled oscillators
      driven only by additive noises, when F=0 a transport may emerge if the nonzero
      mean field breaks the symmetry of the systems. With varying F a continuous or
      discontinuous transition between state s>0 and state s<0 will appear. The mean
      field or current sometimes exhibits hysteresis as a function of F.

PMID- 11461225
TI  - Canonical and noncanonical equilibrium distribution.
AB  - We address the problem of the dynamical foundation of noncanonical equilibrium.
      We consider, as a source of divergence from ordinary statistical mechanics, the
      breakdown of the condition of time scale separation between microscopic and
      macroscopic dynamics. We show that this breakdown has the effect of producing a
      significant deviation from the canonical prescription. We also show that, while
      the canonical equilibrium can be reached with no apparent dependence on dynamics,
      the specific form of noncanonical equilibrium is, in fact, determined by
      dynamics. We consider the special case where the thermal reservoir driving the
      system of interest to equilibrium is a generator of intermittent fluctuations. We
      assess the form of the noncanonical equilibrium reached by the system in this
      case. Using both theoretical and numerical arguments we demonstrate that Levy
      statistics are the best description of the dynamics and that the Levy
      distribution is the correct basin of attraction. We also show that the correct
      path to noncanonical equilibrium by means of strictly thermodynamic arguments has
      not yet been found, and that further research has to be done to establish a
      connection between dynamics and thermodynamics.

PMID- 11461226
TI  - Master-slave synchronization in chaotic discrete-time oscillators.
AB  - In this paper, we study a simple discrete-time neural oscillator model that, in
      certain parameter regimes, exhibits periodic or chaotic dynamics. The present
      model with intrinsically chaotic dynamics is capable of spatiotemporal
      information processing: in response to constant external stimulation, the
      oscillator can switch into different chaotic states restricted to distinct parts
      of the phase space. Of particular interest is the processing of time-dependent
      input in a master-slave configuration of two coupled oscillators. Here, the
      response of an oscillator is studied by driving it with the signal of the other.
      Following the input, the response system adapts to the state of the drive. For a
      chaotic drive, we can observe generalized synchronization. The onset of
      adaptation to the drive state by the response is accompanied by on-off
      intermittency resulting in irregular bursting behavior.

PMID- 11461227
TI  - Glass transition in protein hydration water.
AB  - A model of two-dimensional water is studied in order to analyze recent dielectric
      measurements on protein hydration water. The frustration introduced by the
      coupling of the water molecules to the protein surface prevents a true
      crystallization and induces a smooth transition to a glassy state that is
      detected by its structure factor and the stretched exponential behavior of the
      cage correlation function that measures the rate of change of the hydrogen bond
      network around each molecule. The spectrum of the fluctuations in the vicinity of
      the glass transition exhibits 1/f(alpha) noise in agreement with the dielectric
      measurements. The results suggest that two-dimensional water, which can be probed
      by dielectric measurements, could be an interesting system to study the glassy
      behavior of water.

PMID- 11461228
TI  - Integrated random processes exhibiting long tails, finite moments, and power-law
      spectra.
AB  - A dynamical model based on a continuous addition of colored shot noises is
      presented. The resulting process is colored and non-Gaussian. A general
      expression for the characteristic function of the process is obtained, which,
      after a scaling assumption, takes on a form that is the basis of the results
      derived in the rest of the paper. One of these is an expansion for the cumulants,
      which are all finite, subject to mild conditions on the functions defining the
      process. This is in contrast with the Levy distribution--which can be obtained
      from our model in certain limits--which has no finite moments. The evaluation of
      the spectral density and the form of the probability density function in the
      tails of the distribution shows that the model exhibits a power-law spectrum and
      long tails in a natural way. A careful analysis of the characteristic function
      shows that it may be separated into a part representing a Levy process together
      with another part representing the deviation of our model from the Levy process.
      This allows our process to be viewed as a generalization of the Levy process that
      has finite moments.

PMID- 11461229
TI  - Exact T=0 partition functions for Potts antiferromagnets on sections of the
      simple cubic lattice.
AB  - We present exact solutions for the zero-temperature partition function of the q
      state Potts antiferromagnet (equivalently, the chromatic polynomial P) on tube
      sections of the simple cubic lattice of fixed transverse size Lx x L(y) and
      arbitrarily great length L(z), for sizes Lx x L(y)=2 x 3 and 2 x 4 and boundary
      conditions (a) (FBC(x),FBC(y),FBC(z)) and (b) (PBC(x),FBC(y),FBC(z)), where FBC
      (PBC) denote free (periodic) boundary conditions. In the limit of infinite
      length, L(z)-->infinity, we calculate the resultant ground-state degeneracy per
      site W (=exponent of the ground-state entropy). Generalizing q from Z+ to C, we
      determine the analytic structure of W and the related singular locus Beta which
      is the continuous accumulation set of zeros of the chromatic polynomial. For the
      L(z)-->infinity limit of a given family of lattice sections, W is analytic for
      real q down to a value q(c). We determine the values of q(c) for the lattice
      sections considered and address the question of the value of q(c) for a d
      dimensional Cartesian lattice. Analogous results are presented for a tube of
      arbitrarily great length whose transverse cross section is formed from the
      complete bipartite graph K(m,m).

PMID- 11461230
TI  - Microscopic approach for the site distribution and thermodynamic properties of a
      single-component polymer subjected to an external field.
AB  - A microscopic statistical mechanics approach is proposed for a nonuniform single
      component freely jointed tangential hard-sphere polymer in the framework of
      density-functional theory. The present approach avoids the use of single-chain
      simulation in the theory by treating bonding interaction on the basis of the
      properties of the Dirac delta function. The present excess free energy includes
      all terms of functional perturbative expansion around the uniform bulk fluid in
      the form of the Verlet-modified bridge function. The second-order direct
      correlation function of a uniform polymer melt as the input parameter is obtained
      by solving numerically the polymer-reference-interaction-site-model integral
      equation with the Percus-Yevick closure. Predictions of the present approach for
      such microscopic structural and thermodynamics properties as the site density
      distribution, the partition coefficient, and the adsorption isotherm near a hard
      wall or between two hard walls are compared with computer-simulation results and
      with those of previous theories. The comparison indicates that the present
      approach is more accurate than the previous integral equation theory and the most
      accurate Monte Carlo density-functional theories. The predicted oscillations of
      the medium-induced force between two hard walls immersed in polymer melts are
      consistent with the experimental results available in the literature. The
      relation of the present approach with self-consistent-field theory, as well as
      the differences between the two, are discussed.

PMID- 11461231
TI  - Transport of particles for a spatially periodic stochastic system with correlated
      noises.
AB  - The transport of particles for a spatially periodic stochastic system driven by
      two multiplicative noises and one additive noise (between which there are
      correlations) is investigated for the overdamped and underdamped cases. It is
      shown that (i) the probability current can be positive, zero, or negative; (ii)
      the movement of the particles represents the phenomenon of resonance as a
      function of the additive noise strength. For the underdamped case, the particles
      with different mass can be separated by controlling the system or the noise
      parameters. In particular, a reversal of the flux can be induced by controlling
      the correlations between the additive and multiplicative noises.

PMID- 11461232
TI  - Effect of trends on detrended fluctuation analysis.
AB  - Detrended fluctuation analysis (DFA) is a scaling analysis method used to
      estimate long-range power-law correlation exponents in noisy signals. Many noisy
      signals in real systems display trends, so that the scaling results obtained from
      the DFA method become difficult to analyze. We systematically study the effects
      of three types of trends--linear, periodic, and power-law trends, and offer
      examples where these trends are likely to occur in real data. We compare the
      difference between the scaling results for artificially generated correlated
      noise and correlated noise with a trend, and study how trends lead to the
      appearance of crossovers in the scaling behavior. We find that crossovers result
      from the competition between the scaling of the noise and the "apparent" scaling
      of the trend. We study how the characteristics of these crossovers depend on (i)
      the slope of the linear trend; (ii) the amplitude and period of the periodic
      trend; (iii) the amplitude and power of the power-law trend, and (iv) the length
      as well as the correlation properties of the noise. Surprisingly, we find that
      the crossovers in the scaling of noisy signals with trends also follow scaling
      laws--i.e., long-range power-law dependence of the position of the crossover on
      the parameters of the trends. We show that the DFA result of noise with a trend
      can be exactly determined by the superposition of the separate results of the DFA
      on the noise and on the trend, assuming that the noise and the trend are not
      correlated. If this superposition rule is not followed, this is an indication
      that the noise and the superposed trend are not independent, so that removing the
      trend could lead to changes in the correlation properties of the noise. In
      addition, we show how to use DFA appropriately to minimize the effects of trends,
      how to recognize if a crossover indicates indeed a transition from one type to a
      different type of underlying correlation, or if the crossover is due to a trend
      without any transition in the dynamical properties of the noise.

PMID- 11461233
TI  - Dissipation in Laplacian fields across irregular boundaries.
AB  - The entropy production associated to a Laplacian field distributed across
      irregular boundaries is studied. In the context of the active zone approximation
      an explicit expression is given for the entropy production in terms of geometry,
      whose relation to the variational formulation is discussed. It is shown that the
      entropy production diminishes for successive prefractal generations of the same
      fractal generator, so that the final fractal object is expected to dissipate less
      than all previous ones. The relevance of this result in the abundance of fractal
      surfaces or interfaces observed in nature is discussed.

PMID- 11461234
TI  - Thermophysical properties of gases, liquids, and solids composed of particles
      interacting with a short-range attractive potential.
AB  - A short-range polynomial interaction potential is introduced which has both a
      repulsive core and an attractive part. It is cut off smoothly such that its first
      and second derivatives vanish at the cutoff distance. The potential therefore
      enables efficient simulation studies of a model material that exhibits
      similarities to a full (but computationally expensive) classical Lennard-Jones
      system. Thermophysical properties of the model are calculated by (nonequilibrium)
      molecular dynamics computer simulations and compared with analytical results.
      Among the quantities studied is the pressure as a function of the density for
      various temperatures. Equations of state for the fluid and the solid are tested.
      The coexistence of gaseous, (metastable) liquid, and fcc solid phases is found
      for a range of temperatures. Bulk and shear moduli are computed. The response of
      the system to a shear deformation with a constant shear rate is analyzed. The
      liquid shows viscoelastic behavior that can be described with a Maxwell model.
      The solid behaves as an elastic medium up to a finite deformation and then
      undergoes a transition to plastic flow, which is stick-slip-like at small shear
      rates and continuous at higher ones.

PMID- 11461235
TI  - Sliding lubricated anisotropic rough surfaces.
AB  - The object of this paper is to study the effects of lubricant film flow,
      pressurized and sheared between two parallel rough surfaces in sliding motion.
      The influence of microscopic surface roughness on lubricant film flow macroscopic
      behavior is described through five nondimensional parameters called flow factors.
      These macroscopic transport parameters are related to the local geometry of
      apertures and surfaces. Short- and long-range-correlated surface roughnesses
      display very different macroscopic behaviors when surfaces are close to contact.
      These behaviors are related to underlying surface roughness parameters such as
      the correlation length and the self-affine Hurst exponent. The problem is
      numerically studied, and results are compared to some analytical asymptotic
      results.

PMID- 11461236
TI  - Free-volume viscosity model for fluids in the dense and gaseous states.
AB  - A free-volume and friction viscosity model is presented versus pressure and
      temperature, valid for both gaseous and dense fluids. This model involves only
      three adjustable parameters for each pure compound. It is able to represent the
      gas-liquid transition and the behavior in the supercritical conditions. The model
      has been successfully applied to methane (885 data points for 0.01< or =P< or
      =200 MPa and 90.7< or =T< or =600 K) and to propane (1085 data points for 0.01<
      or =P< or =200 MPa and 90< or =T< or =600 K) in the gaseous and dense states
      (average absolute deviation is 2.59% for methane and 2.50% for propane, with
      maximum deviation of 14.8% for methane and 9.19% for propane). It has also been
      applied to hexane, octane, dodecane, benzene, trans-decaline, and 2,2
      dimethylpropane (903 data points) in a large pressure range (up to 505.5 MPa).
      Considering these compounds the maximum deviation is 19.5% (for octane) and the
      average deviation is 3.51% in the worst case (dodecane, which has data points up
      to 501.6 MPa).

PMID- 11461237
TI  - Instanton solutions in the problem of wrinkled flame-front dynamics.
AB  - The statistics of the slopes of wrinkling flames propagating through an
      infinitely wide channel is investigated by the quantum-field-theory methods. We
      dwell on the WKB approximation in the functional integral, which is analogous to
      the Wyld functional integral in turbulence. The main contribution to statistics
      is due to a coupled field-force configuration. This configuration is related to a
      kink between metastable exact pole solutions of the Sivashinsky equation. These
      kinks are responsible for both the formation of new cusps and the rapid power-law
      acceleration of the mean flame front. The problem of asymptotic stability of the
      solutions is discussed.

PMID- 11461238
TI  - Observation of single transits in supercooled monatomic liquids.
AB  - A transit is the motion of a system from one many-particle potential energy
      valley to another. We report the observation of transits in molecular dynamics
      calculations of supercooled liquid argon and sodium. Each transit is a correlated
      simultaneous shift in the equilibrium positions of a small local group of
      particles, as revealed in the fluctuating graphs of the particle coordinates
      versus time. To the best of our knowledge, this is the first reported direct
      observation of transit motion in a monatomic liquid in thermal equilibrium. We
      found transits involving 2-11 particles, having mean shift in equilibrium
      position on the order of 0.4R(1) in argon and 0.25R(1) in sodium, where R1 is the
      nearest neighbor distance. The time it takes for a transit to occur is
      approximately one mean vibrational period, confirming that transits are fast.

PMID- 11461239
TI  - Asymmetric primitive-model electrolytes: Debye-Huckel theory, criticality, and
      energy bounds.
AB  - Debye-Huckel (DH) theory is extended to treat two-component size- and charge
      asymmetric primitive models, focusing primarily on the 1:1 additive hard-sphere
      electrolyte with, say, negative ion diameters a(--) larger than the positive ion
      diameters a(++). The treatment highlights the crucial importance of the charge
      unbalanced "border zones" around each ion into which other ions of only one
      species may penetrate. Extensions of the DH approach that describe the border
      zones in a physically reasonable way are exact at high T and low density rho and,
      furthermore, are also in substantial agreement with recent simulation predictions
      for trends in the critical parameters, T(c) and rho(c), with increasing size
      asymmetry. Conversely, the simplest linear asymmetric DH description, which fails
      to account for physically expected behavior in the border zones at low T, can
      violate a new lower bound on the energy (which applies generally to models
      asymmetric in both charge and size). Other theories, including those based on the
      mean spherical approximation, predict trends in the critical parameters quite
      opposite to those established by the simulations.

PMID- 11461240
TI  - Computation of the viscosity of a liquid from time averages of stress
      fluctuations.
AB  - The shear viscosity can be calculated from the standard deviation of an
      equilibrium ensemble of time averages of the shear stress computed along finite
      duration phase space trajectory segments. The mean square of the segment averages
      of the shear stress is proportional to the shear viscosity and inversely
      proportional to the duration of the trajectory segments and the number of
      particles. We test the fluctuation relation for the shear viscosity and show that
      it provides a simple but viable means of computing the zero strain rate shear
      viscosity. We decompose the shear viscosity computed using this fluctuation
      method, into its "kinetic" and "configurational" components. We also calculate
      the relevant relaxation times. We compare the computed results with standard
      nonequilibrium molecular dynamics simulations. Finally we compute the bulk
      viscosity using an analogous fluctuation method.

PMID- 11461241
TI  - Lattice Boltzmann equation hydrodynamics.
AB  - By inserting position and time dependent "source" or "forcing" terms into the
      microscopic evolution equation of a lattice Boltzmann fluid and treating the
      generalized scheme within the usual Chapman-Enskog methodology, we show that the
      emergent dynamics of the lattice fluid may be usefully transformed. Our method of
      adjustment is demonstrated by implementing the cylindrical polar coordinate form
      of the continuity and momentum equations on a rectangular lattice and generating
      results for pipe flow. With straightforward systematic adjustment of the
      simulation, our approach produces results in excellent agreement with theory.

PMID- 11461242
TI  - Thermodynamically consistent incorporation of the Schneider rate equations into
      two-phase models.
AB  - We formulate a solid-liquid two-phase model including viscous stresses, heat
      conduction in the two phases, as well as heat exchange through the interface, and
      a phase change in the structure of nonequilibrium thermodynamics described by a
      general equation for the nonequilibrium reversible-irreversible coupling
      (GENERIC). The evolution of the microstructure is studied in terms of the
      Schneider rate equations introducing the nucleation rate and the radial growth
      rate of the solid phase. The application of the GENERIC structure shows that this
      radial growth factor is not an additional, independent material function but is
      to be expressed in terms of the difference in the chemical potentials, in the
      temperatures, and in the pressures between the two phases. The contribution due
      to the pressure difference appears in conjunction with the surface tension in
      such a way, that a driving force results only if deviations from a generalized
      version of the Laplace equation occur. Furthermore, it is found that for
      conditions under which the radial growth rate is zero, the nucleation rate must
      vanish.

PMID- 11461243
TI  - Driven granular gases with gravity.
AB  - We study fluidized granular gases in a stationary state determined by the balance
      between external driving and bulk dissipation. The two considered situations are
      inspired by recent experiments, where gravity plays a major role as a driving
      mechanism: in the first case, gravity acts only in one direction and the bottom
      wall is vibrated; in the second case, gravity acts in both directions and no
      vibrating walls are present. Simulations performed under the molecular chaos
      assumption show averaged profiles of density, velocity, and granular temperature
      that are in good agreement with the experiments. Moreover, we measure velocity
      distributions that show strong non-Gaussian behavior, as experiments pointed out,
      but also density correlations accounting for clustering, at odds with the
      experimental results. The hydrodynamics of the first model is discussed and an
      exact solution is found for the density and granular temperature as functions of
      the distance from the vibrating wall. The limitations of such a solution, in
      particular in a broad layer near the wall injecting energy, are discussed.

PMID- 11461244
TI  - Modes of granular segregation in a noncircular rotating cylinder.
AB  - Axial segregation is a well-known example of segregation of granular materials.
      However, at present, there is no conclusive explanation as to why it occurs. Most
      studies of axial segregation to date are based on cylinders with circular cross
      sections, and models focus on the character of the surface flow without
      accounting explicitly for the influence of any subsurface detail. The present
      experiments demonstrate that the cross section of the mixer has a significant
      influence on axial segregation and that subsurface dynamics are, in fact,
      important. Unlike circular mixers, in square mixers the subsurface segregation
      patterns change with filling level, as does the time dependence of axial
      segregation. Furthermore, when radial segregation patterns in noncircular mixers
      most closely resemble that observed for circular cylinders, the time dependence
      for axial band formation deviates the most. These results challenge segregation
      theories of axial segregation that ignore subsurface effects.

PMID- 11461245
TI  - Dispersion in poroelastic systems.
AB  - We address one key source of the known discrepancies between theory and
      experiment in poroelasticity, i.e., the fact that Gassmann's equations for the
      bulk and shear moduli predict that the shear modulus is independent of the
      saturating fluid properties, whereas it is observed on the contrary that at high
      enough frequencies the shear modulus can in fact depend on the fluid's elastic
      properties in many porous materials. One clue to understanding this behavior
      comes from effective medium theory, which shows that the shear modulus does
      depend on the fluid properties in many circumstances. In comparison to values
      predicted by effective medium theory, Gassmann's equations predict different,
      smaller values for both the effective bulk and shear moduli of porous media.
      Sorting through these apparent (but not actual) disagreements among theory and
      theory, and theory and experiment is the main thrust of the paper.

PMID- 11461246
TI  - Stratified horizontal flow in vertically vibrated granular layers.
AB  - A layer of granular material on a vertically vibrating sawtooth-shaped base
      exhibits horizontal flow whose speed and direction depend on the parameters
      specifying the system in a complex manner. Discrete-particle simulations reveal
      that the induced flow rate varies with height within the granular layer and
      oppositely directed flows can occur at different levels. The behavior of the
      overall flow is readily understood once this feature is taken into account.

PMID- 11461247
TI  - Fracture mechanics of snow avalanches.
AB  - Dense snow avalanches are analyzed by modeling the snow slab as an elastic and
      brittle plate, attached by static friction to the underlying ground. The grade of
      heterogeneity in the local fracture (slip) thresholds, and the ratio of the
      average substrate slip threshold to the average slab fracture threshold, are the
      decisive parameters for avalanche dynamics. For a strong pack of snow there
      appears a stable precursor of local slips when the frictional contacts are
      weakened (equivalent to rising temperature), which eventually trigger a
      catastrophic crack growth that suddenly releases the entire slab. In the opposite
      limit of very high slip thresholds, the slab simply melts when the temperature is
      increased. In the intermediate regime, and for a homogeneous slab, the model
      display features typical of real snow avalanches. The model also suggests an
      explanation to why avalanches are impossible to forecast reliably based on
      precursor observations. This explanation may as well be applicable to other
      catastrophic rupture phenomena such as earthquakes.

PMID- 11461248
TI  - Vibration-induced jamming transition in granular media.
AB  - The quasistatic frequency response of a granular medium is measured by a forced
      torsion oscillator method, with forcing frequency f(p) in the range 10(-4) Hz to
      5 Hz, while weak vibrations at high-frequency f(s), in the range 50 Hz to 200 Hz,
      are generated by an external shaker. The intensity of vibration Gamma is below
      the fluidization limit. A loss factor peak is observed in the oscillator response
      as a function of Gamma or f(p). In a plot of ln f(p) against 1/Gamma, the
      position of the peak follows an Arrhenius-like behavior over four orders of
      magnitude in f(p). The data can be described as a stochastic hopping process
      involving a probability factor exp(-Gamma(j)/Gamma) with Gamma(j) a f(s)
      dependent characteristic vibration intensity. An f(s)-independent description is
      given by exp(-tau(j)/tau), with tau(j) an intrinsic characteristic time, and
      tau=Gamma(n)/2pif(s), n=0.5-0.6, an empirical control parameter with unit of
      time. tau is seen as the effective average time during which the perturbed grains
      can undergo structural rearrangement. The loss factor peak appears as a crossover
      in the dynamic behavior of the vibrated granular system, which, at the time scale
      1/f(p), is solid-like at low Gamma, and the oscillator is jammed into the
      granular material, and is fluid-like at high Gamma, where the oscillator can
      slide viscously.

PMID- 11461249
TI  - Segregation of granular media by diffusion and convection.
AB  - A diffusion-convection equation is used to model granular segregation within a
      mixture of particles of different size, shape, or surface structure in a vertical
      vessel. Convection describes competition between species in vertical direction
      whereas random noise (shaking) allows particles to exchange positions. For two
      species it is shown that the moving grains converge to a unique distribution
      along the vertical scale. For more than two species it is shown that at least one
      equilibrium distribution exists (there are examples with multiple equilibria).
      For a class of models with simple competition laws, uniqueness of the equilibrium
      in all dimensions is shown.

PMID- 11461250
TI  - Scaling properties of granular materials.
AB  - Given an assembly of viscoelastic spheres with certain material properties, we
      raise the question how the macroscopic properties of the assembly will change if
      all lengths of the system, i.e. radii, container size etc., are scaled by a
      constant. The result leads to a method to scale down experiments to lab size.

PMID- 11461251
TI  - Measurement of long-range steric repulsions between microspheres due to an
      adsorbed polymer.
AB  - We have measured the interparticle potential between pairs of micron-sized silica
      spheres induced by adsorbed polyethylene oxide polymer using a line-scanned
      optical tweezer. We found this long-range steric repulsion to be exponential over
      the range of energies (0.1k(B)T-5k(B)T) and polymer molecular weights (452,000
      1,580,000) studied, and that the potential scaled with the polymer's radius of
      gyration R(G). The potential's exponential decay length was about 0.6R(G) and its
      range was about 4R(G), although both parameters varied significantly from one
      pair of spheres to another. The potential's exponential prefactor was greater
      than mean-field predictions.

PMID- 11461252
TI  - Entropy-driven phase transition in binary mixtures.
AB  - Based on the principle of entropy maximum, a transparent method to study the
      phase separation is proposed. The excluded volume effects of binary mixtures of
      hard spheres with two different diameters are analyzed and the role of entropy is
      emphasized. As a result of the entropy variation caused by the packing of large
      spheres, there is a critical volume fraction to denote the phase boundary. It is
      shown that the variation of free volume fraction is influenced by the ratio
      alpha=d(L)/d(S) of large to small sphere diameters and the ratio
      x=eta(L)/(eta(L)+eta(S)) of large-sphere volume fraction to the total volume
      fraction of large- and small-spheres. We introduce a modification factor beta to
      describe the overlap degree of two large spheres excluded volumes when they pack
      together. The critical volume fractions for large-sphere packing with different
      values of alpha and x are calculated, and the corresponding phase boundaries are
      determined. Our results are in quite good agreement with previous experimental
      measurements.

PMID- 11461253
TI  - Accurate calculation of three-body depletion interactions.
AB  - We compute three-body depletion interactions in a hard-sphere mixture within the
      framework of density-functional theory and by considering the infinite dilution
      limit of the functional. The results look very accurate and show three-body
      interactions much smaller than the pair depletion ones, revealing that these are
      strongly influenced by correlations and have a decay length similar to the two
      body depletion potential. The results are compared with the predictions of the
      Asakura-Oosawa model for the triplet interactions.

PMID- 11461254
TI  - Diffusive growth of polydisperse hard-sphere crystals.
AB  - Unlike atoms, colloidal particles are not identical, but can only be synthesised
      within a finite size tolerance. Colloids are therefore polydisperse, i.e.,
      mixtures of infinitely many components with sizes drawn from a continuous
      distribution. We model the crystallization of hard-sphere colloids (with/without
      attractions) from an initially amorphous phase. Although the polydisperse hard
      sphere phase diagram has been widely studied, it is not straightforwardly
      applicable to real colloidal crystals, since they are inevitably out of
      equilibrium. The process by which colloidal crystals form determines the size
      distribution of the particles that comprise them. Once frozen into the crystal
      lattice, the particles are caged so that the composition cannot subsequently
      relax to the equilibrium optimum. We predict that the mean size of colloidal
      particles incorporated into a crystal is smaller than anticipated by equilibrium
      calculations. This is because small particles diffuse fastest and therefore
      arrive at the crystal in disproportionate abundance.

PMID- 11461255
TI  - Sedimentation profiles of systems with reentrant melting behavior.
AB  - We examine sedimentation density profiles of star polymer solutions as an example
      of colloidal systems in sedimentation equilibrium that exhibit reentrant melting
      in their bulk phase diagram. Phase transitions between a fluid and a fluid with
      an intercalated solid are observed below a critical gravitational strength
      alpha*. Characteristics of the two fluid-solid interfaces in the density profiles
      occurring in Monte Carlo simulations for alpha<alpha* are in agreement with
      scaling laws put forth in the framework of a phenomenological theory.
      Furthermore, we detect density oscillations at the fluid-gas interface at high
      altitudes for high-gravitational fields, which are verified with density
      functional theory and should be observable in surface scattering experiments.

PMID- 11461256
TI  - Shear banding and the isotropic-to-nematic transition in wormlike micelles.
AB  - Using deuterium NMR spectroscopy in a Couette cell, we observe shear-induced
      nematic ordering in the concentrated wormlike-micelle system CTAB/D(2)O, and our
      results are qualitatively consistent with birefringence studies, and in exact
      quantitative agreement with the degree of order measured in neutron-diffraction
      measurements. The width of the nematic region depends on shear rate, as well as
      on the temperature proximity to the equilibrium isotropic-nematic transition.
      Comparison of the nematic order profiles with velocity profiles obtained under
      identical conditions shows quite clearly that the nematic state is not
      identifiable with a highly sheared, low viscosity layer, and we conclude that the
      process of shearing induces a nematic state of high viscosity, possibly
      associated with mesoscale ordering. We present a simple model in which transition
      from the high shear branch to the viscous nematic branch is counterbalanced by
      subsequent relaxation of nematic order.

PMID- 11461257
TI  - Phase diagram of a symmetric binary fluid in a porous matrix.
AB  - The phase behavior of a binary symmetric fluid in thermal equilibrium with a
      porous matrix has been studied with the optimized random phase approximation and
      grand canonical Monte Carlo simulations. Depending on the matrix properties and
      the matrix-fluid and fluid-fluid interactions we find three types of phase
      diagram characterized by a tricritical point, a tricritical point with a triple
      point, or a critical end point. Small changes in the properties of the matrix or
      in the interactions are demonstrated to lead to drastic modifications of the
      phase diagram of the fluid, in qualitative agreement with observations in
      experimental studies. We show, in particular, that the change between the
      different types of phase diagram is triggered not only by the fluid-fluid
      interactions (internal parameters) but also by the properties of the matrix and
      of the matrix-fluid potentials (external parameters).

PMID- 11461258
TI  - Mean-squared displacement of a molecule moving in a glassy system.
AB  - The mean-squared displacement (MSD) of a hard sphere and of a dumbbell molecule
      consisting of two fused hard spheres immersed in a dense hard-sphere system is
      calculated within the mode-coupling theory for ideal liquid-glass transitions. It
      is proven that the velocity correlator, which is the second time derivative of
      the MSD, is the negative of a completely monotone function for times within the
      structural-relaxation regime. The MSD is found to exhibit a large time interval
      for structural relaxation prior to the onset of the alpha process, which cannot
      be described by the asymptotic formulas for the mode-coupling-theory-bifurcation
      dynamics. The alpha process for molecules with a large elongation is shown to
      exhibit an anomalously wide crossover interval between the end of the von
      Schweidler decay and the beginning of normal diffusion. The diffusivity of the
      molecule is predicted to vary nonmonotonically as a function of its elongation.

PMID- 11461259
TI  - Microstructural shear localization in plastic deformation of amorphous solids.
AB  - The shear-transformation-zone (STZ) theory of plastic deformation predicts that
      sufficiently soft, noncrystalline solids are linearly unstable against forming
      periodic arrays of microstructural shear bands. A limited nonlinear analysis
      indicates that this instability may be the mechanism responsible for strain
      softening in both constant-stress and constant-strain-rate experiments. The
      analysis presented here pertains only to one-dimensional banding patterns in two
      dimensional systems, and only to very low temperatures. It uses the rudimentary
      form of the STZ theory in which there is only a single kind of zone rather than a
      distribution of them with a range of transformation rates. Nevertheless, the
      results are in qualitative agreement with essential features of the available
      experimental data. The nonlinear theory also implies that harder materials, which
      do not undergo a microstructural instability, may form isolated shear bands in
      weak regions or, perhaps, at points of concentrated stress.

PMID- 11461260
TI  - Ribbon phase in a phase-separated lyotropic lamellar-sponge mixture under shear
      flow.
AB  - We report the effect of shear flow on a phase-separated system composed of
      lyotropic lamellar (L(alpha)) and sponge (L3) phases in a mixture of brine,
      surfactant, and cosurfactant. Optical microscopy, small-angle light, and x-ray
      scattering measurements are consistent with the existence of a steady state made
      of multilamellar ribbon-like structures aligned in the flow direction. At high
      shear rates, these ribbon-like structures become unstable and break up into
      monodisperse droplets resulting in a shear-thickening transition.

PMID- 11461261
TI  - Experimental study on the fluctuations of dipolar chains.
AB  - Dynamic light scattering is used to study experimentally the dynamics of dipolar
      chains consisting of ferrofluid particles subjected to a magnetic field (H0). The
      effective diffusion coefficient shows a pronounced dependence on the scattering
      wave vector q, reflecting two modes of motion: translational diffusion of the
      whole chain, and fluctuations of particles within a chain. The characteristic
      probed frequency of particle displacements is inversely proportional to H0, and
      exhibits a q(3) dependency. Based on the striking analogy to polymer chain
      dynamics, we attribute these behaviors to the contribution of hydrodynamic
      interactions (HI's) that couples particles motion within a chain. This work
      suggests that chain fluctuations cannot be ignored even for the very strong
      magnetic field applied (coupling constant<10(6)). HI's can still be important,
      even at an extremely low particle volume fraction of 10(-5).

PMID- 11461262
TI  - Dipolar and chain-linking effects on the rheology of grafted chains in a nanopore
      under shear at different grafting densities.
AB  - Nonequilibrium molecular dynamics simulations are applied to investigate the
      rheological properties of coplanar nanopore systems of amphiphilic chain
      molecules with the tails grafted to the walls of the nanopore and with the head
      group ends immersed in a solvent inside the nanopore. In particular, the effects
      of modifying the interaction between the amphiphilic head-groups by repulsive
      dipolar interactions or directly covalently linking pairs of chains at the head
      groups have been studied. Different grafting densities are considered. The chains
      are modeled by a harmonic bead-spring model, and all particles interact through
      the repulsive part of a shifted Lennard-Jones potential. Head-group linking is
      also governed by a bead-spring potential. A harmonic potential models the lattice
      vibrations of the atomic boundaries. The rheological properties are studied by a
      shearing process in which the heat generated is conducted away from the system
      through the walls by applying a Nose-Hoover thermostat. Computed geometric
      parameters such as average chain length and average tilt angle indicate reduction
      in chain flexibility at large dipole moments. Dipolar repulsion is found to
      broaden the density profiles of the solvent. This effect is opposed by chain
      linking. For increasing head-group repulsion, the amphiphile-solvent interfaces
      become less diffusive that leads to systematic variations in viscosities with
      increasing dipole moments. Friction forces become stronger at large grafting
      density and for larger dipole moments. The changes in rheological properties for
      fixed grafting density are essentially governed by the change in the response of
      the normal pressure to the applied shear field. The velocity gradients depend
      strongly on the degree of grafting density but appear to be less sensitive to the
      strength of the interactions between the head groups.

PMID- 11461263
TI  - Effective temperatures in an exactly solvable model for a fragile glass.
AB  - A model glass with facilitated dynamics is considered with one type of fast
      process (beta type) and one type of slow process (alpha type). On time scales
      where the fast processes are in equilibrium, the slow ones have a dynamics that
      resembles that of facilitated spin models. The main features are the occurrence
      of a Kauzmann transition, a Vogel-Fulcher-Tammann-Hesse behavior for the
      relaxation time, an Adam-Gibbs relation between relaxation time and
      configurational entropy, and an aging regime. The model is such that its statics
      is simple and its (Monte Carlo type) dynamics is exactly solvable. The dynamics
      has been studied both on the approach to the Kauzmann transition and below it. In
      certain parameter regimes it is so slow that a quasiequilibrium occurs at a time
      dependent effective temperature. Correlation and response functions are also
      computed, as well as the out of equilibrium fluctuation-dissipation relation,
      showing the uniqueness of the effective temperature, thus giving support to the
      rephrasing of the problem within the framework of out of equilibrium
      thermodynamics.

PMID- 11461264
TI  - Equilibrium of drops on inclined hydrophilic surfaces.
AB  - Why does not gravity make drops slip down the inclined surfaces, e.g., plant
      leaves? The current explanation is based on the existence of surface
      inhomogeneities, which cause a sustaining force that pins the contact line.
      Following this theory, the drop remains in equilibrium until a critical value of
      the sustaining force is reached. We propose an alternative analysis, from the
      point of view of energy balance, for the particular case in which the drop leaves
      a liquid film behind. The critical angle of the inclined surface at which the
      drop slips down is predicted. This result does not depend explicitly on surface
      inhomogeneities, but only on the drop size and surface tensions. There is good
      agreement with experiments for contact angles below 90 degrees where the
      formation of the film is expected, whereas for greater contact angles great
      discrepancies arise.

PMID- 11461265
TI  - Density functional theories and molecular simulations of adsorption and phase
      transitions in nanopores.
AB  - The nonlocal density functional theory (NLDFT) of confined fluids is tested
      against Monte Carlo simulations by using the example of Lennard-Jones (LJ) fluid
      sorption in slit-shaped and cylindrical nanopores ranging from 0.3 to 10 nm in
      width. The fluid-fluid and solid-fluid parameters of the LJ potentials were
      chosen to represent several experimentally important adsorption systems: nitrogen
      and carbon dioxide in activated carbons, zeolites, and mesoporous molecular
      sieves of the MCM-41 type. Freezing in nanopores is discussed using the example
      of methane sorption in carbon at 111 K. Comparison with reference experiments is
      given when available. Two versions of NLDFT, the smoothed density approximation
      and the fundamental measure theory, are considered. It is shown that NLDFT
      approaches with properly chosen parameters provide quantitative agreement with
      the results of Monte Carlo simulations and reference experiments. Appreciable
      deviations are found in extremely narrow pores of less than two molecular
      diameters in width. In wider pores, NLDFT models can be used for quantitative
      predictions of reversible and hysteretic adsorption isotherms and analyses of the
      specifics of phase transformations, including the equilibrium and spinodal phase
      transitions.

PMID- 11461266
TI  - Dynamic, self-assembled aggregates of magnetized, millimeter-sized objects
      rotating at the liquid-air interface: macroscopic, two-dimensional classical
      artificial atoms and molecules.
AB  - This paper describes self-assembly of millimeter-sized, magnetized disks floating
      on a liquid-air interface, and rotating under the influence of a rotating
      external magnetic field. Spinning of the disks results in hydrodynamic repulsion
      between them, while the rotating magnetic field produces an average confining
      potential acting on all disks. The interplay between hydrodynamic and magnetic
      interactions leads to the formation of patterns. Theoretical analysis of
      hydrodynamic and magnetic forces indicates that the interactions in this system
      are similar to those acting in systems of finite numbers of particles behaving
      classically ("classical artificial atoms"). Macroscopic artificial atoms and
      molecules are described, and the rules governing their morphologies outlined.

PMID- 11461267
TI  - Fluctuation-induced constraints on the observation of unbinding in a confined
      complex fluid.
AB  - An extensive study of the effect of fluctuations on the unbinding of an interface
      from a wall in a ternary system is presented. The framework upon which the
      analysis is based is a linear functional renormalization group scheme of the
      appropriate effective interface Hamiltonian. The interface model includes
      position-dependent gradient coefficients, and their presence is shown to be
      equivalent to modifications of the bare interface potential that are highly
      relevant in determining the renormalized critical behavior. We analyze the
      modified interface potential in a mean-field-like way for both bare critical and
      first-order unbinding transitions in order to highlight the key effects. We
      further perform a detailed study of the linearized renormalization group
      equations identifying three fluctuation regimes and recovering earlier
      predictions for nonuniversal critical exponents. The surface phase diagram
      changes dramatically under renormalization with, most notably, fluctuation
      induced reentrant behavior. We show that in the revised phase diagram the unbound
      region is limited in extent indicating that the opportunity for observing an
      unbinding transition in a confined complex fluid is highly restricted.

PMID- 11461268
TI  - Interfacial water dielectric-permittivity-profile measurements using atomic force
      microscopy.
AB  - The arrangement of water molecules at charged aqueous interfaces is an important
      question in biology, electrochemistry, and geochemistry. Theoretical studies
      suggest that the molecules become arranged in several layers adjacent to a solid
      interface. Using atomic force microscopy we have measured the water dielectric
      permittivity profile perpendicular to mica surfaces. The measured variable
      permittivity profile starting at epsilon approximately 4 at the interface and
      increasing to epsilon=80 about 10 nm from the surface suggests a reorientation of
      water molecule dipoles in the presence of the mica interfacial charge.

PMID- 11461269
TI  - Thermal diffuse x-ray scattering in a model columnar liquid crystal.
AB  - The fluctuation correlation functions and the density-density correlation
      functions for a realistic model of a columnar liquid crystal in its helically
      ordered phase are derived. The influence of positional and orientational
      molecular fluctuations on the thermal diffuse x-ray scattering is studied within
      a three-dimensional model of columns inscribed on a triangular lattice. Resulting
      from quasi-long-range ordering, very anisotropic long-tail scattered intensities
      are predicted, giving a nonuniversal signature for the helically ordered columnar
      liquid crystal phase. Scattered intensities both near the Bragg maxima at the
      inverse lattice vectors and at the Bragg condition due to periodic orientational
      ordering are treated. The percolation of the long-range behavior for a screw
      variable composed of two quantities having only quasi-long-range behavior is
      predicted.

PMID- 11461270
TI  - Measurement of the anisotropy of the energy of an isotropic-smectic interface in
      a smectic cylinder: application to the L3-L alpha interface.
AB  - In order to measure the relative anisotropy of a smectic-isotropic interfacial
      energy, we propose an alternative to the classic Wulff construction. We derive
      the Gibbs-Thomson equation that describes the equilibrium of a droplet of
      isotropic phase in a smectic sample confined within a cylindrical capillary. We
      then discuss the influence of the curvature energy term and show that the profile
      of the droplet gives the variation of the surface energy, either analytically or
      by means of a modified Wulff construction. From this approach, we measure the
      relative anisotropy of the sponge-lamellar interfacial energy in the dilute
      Cetylpyridinium Chloride/hexanol/brine surfactant system. We quantitatively
      confirm and complete previous observations of this interface, which displays
      strong crystalline features, such as cusps and forbidden orientations.

PMID- 11461271
TI  - Isotropic-nematic phase transition: Influence of intramolecular flexibility using
      a fused hard sphere model.
AB  - The role of flexibility on the liquid crystal isotropic-nematic phase transition
      has been studied by means of Monte Carlo simulation. We present equations of
      state for the isotropic-nematic branches and, in the isotropic phase, numerically
      calculated values for the virial coefficients B2, B3, and B4. We have studied two
      models: 11 hard sphere monomers fused in a linear configuration with a reduced
      bond length of 0.6 and a 15-monomer version of this model in which monomers at
      one end of the chain become flexible. We have observed spontaneous nematic liquid
      crystal formation for both of the fully rigid models, and also for models with up
      to six flexible monomers in the tail. We conclude that molecular flexibility has
      a strongly destabilizing effect on the nematic phase. This is probably due to the
      decrease in shape anisotropy that flexible tails allow.

PMID- 11461272
TI  - Deterministic numerical model for treating the three elastic constants in nematic
      liquid-crystalline polymers.
AB  - In this paper, a deterministic model, which considers the three Frank elastic
      constants, is introduced. It is based on a lattice model and a director is used
      to represent the orientation of the liquid crystals in each cell. A tensor
      expression of the so-called "texture field" is deduced so that the nematic
      symmetry is conserved automatically. In the current model, the evolution of the
      director field can be viewed as a process towards the state of zero elastic
      torque. The model forms the basis for an improved understanding of the mesoscale
      structures and rheological phenomena of nematic liquid-crystalline polymers. It
      has been tested in its ability to reproduce the Freedericksz transitions, and
      simulations of thin liquid crystalline polymer films clearly show the effect of
      unequal elastic constants on the director microstructure evolution.

PMID- 11461273
TI  - Electro-optic response of a ferroelectric liquid crystal in thick free-standing
      films.
AB  - We study the electro-optic response of a ferroelectric liquid crystal in free
      standing films as thick as the helical pitch. In the films thicker than about one
      pitch, two relaxation modes are observed in the frequency spectra. The relaxation
      frequency of the slower mode decreases when increasing the film thickness, while
      that of the faster mode, which appears at approximately 1 kHz, is almost
      independent of the film thickness. In thinner films, a single relaxation mode is
      observed at several hundred Hz. The obtained relaxation spectra are discussed in
      comparison to the theoretical spectra of the phase mode in a system of finite
      length along the helical axis calculated by Urbanc and Zeks [Phys. Rev. E 52,
      3892 (1995)].

PMID- 11461274
TI  - Effect of pressure on the photoinduced nematic-isotropic phase transition.
AB  - We report the results of high-pressure studies on the photoinduced nematic
      isotropic phase transition. It is observed that pressure has a significant
      influence on the shift in the transition temperature caused by uv radiation. We
      propose a possible mechanism to explain the observed results.

PMID- 11461275
TI  - Gyrotropy problem in nonhomogeneous media: The case of short-pitch chiral-smectic
      C liquid crystals and incommensurate structures.
AB  - The question about the existence of macroscopic models for gyrotropy in
      inhomogeneous materials is examined. We have carried out a detailed polarimetric
      study on a short-pitch chiral-smectic-C liquid crystal, which has been taken as
      an example of an inhomogeneous optical medium. In accordance to the theoretical
      predictions, we have found that, as a first approximation, the inhomogeneous
      liquid crystal can be modeled as a homogeneous uniaxial medium with huge optical
      activity in a direction perpendicular to the optic axis. However, some deviations
      have been determined in the precise values of the optical activity predicted by
      the theory. These discrepancies have been attributed to higher-order gyration
      like effects, which are usually negligible and have not been considered in
      previous theoretical approaches. The agreement improves when these higher-order
      effects are incorporated. In the light of the above results, the theory is
      applied to the case of incommensurate structures. The origin of gyrotropy in
      these materials is clarified, and it is shown that this quantity can be described
      by a usual macroscopic tensor. If the incommensurate structure has an inversion
      center we deduce that all gyration effects rigorously vanish, contrary to the
      opinion maintained by several authors.

PMID- 11461276
TI  - Liquid-crystal-electrochromic-material interface: a p-n-like electro-optic
      junction.
AB  - A liquid crystal (LC) cell has been made by using a standard sandwich
      configuration with one of the indium tin oxide (ITO) electrodes covered by a thin
      layer of tungsten trioxide (WO3). In this kind of cell optical polarization
      switching (observed under a crossed polarizer microscope) occurs for only one of
      the two polarities of an ac external applied electric field, while in the usual
      liquid crystal cells the electro-optic response does not depend on the sign of
      the field. The inhibiting switching configuration corresponds to anodic
      polarization of the tungsten trioxide film in which the deintercalation of
      cations occurs. Here we present the time behavior of charge and discharge for
      both the anodic and cathodic currents. A model based on charge carrier exchange
      between the ITO-WO3 and WO3-LC interfaces and also electrochemical processes is
      reported. Our model is also capable of explaining the electric and electro-optic
      asymmetric responses of the cell. Numerical calculations confirm the model.

PMID- 11461277
TI  - Importance of interactions for free-volume and end-group effects in polymers: an
      equilibrium lattice investigation.
AB  - We consider a lattice model of a polymer system in which we distinguish between
      the end (E) and the middle (M) groups. The free volume is represented as a "hole"
      or "void" (0), which constitutes a separate species in addition to the two
      "species" M and E. There are three different exchange interaction energies, and
      correspondingly three Boltzmann weights w(ij), i not equal j=0,E,M between
      different species. We define the free volume associated with the species j=M or
      E, as the average number of voids next to j. Using a recently developed
      equilibrium lattice theory, we calculate the free volume v(E) and v(M) associated
      with an end group and a middle group, respectively, and investigate the effects
      of interactions among them. Our calculations show that v(E) and v(M) are
      intricate functions of w(ij), the pressure and the molecular weight, and that
      their difference can change sign under certain conditions. These conditions are
      elucidated. We demonstrate that when the end group is chemically dissimilar from
      the middle group, the middle group may have more free volume than the end group.
      We find that the conditions that favor a middle group having more free volume
      over an end group are w(E0)<1, w(M0)<1, and w(ME)>1. The effect of pressure and
      molecular weight can be of either type and appears to be dependent on the
      interactions.

PMID- 11461278
TI  - Mode-coupling theory and polynomial fitting functions: a complex-plane
      representation of dielectric data on polymers.
AB  - Recently, it has been shown that the higher-order A3 and A4 scenarios of the mode
      coupling theory (MCT) are in many cases capable of providing a good description
      of the complicated dielectric spectra often encountered in polymeric systems. In
      this paper, more data from dielectric measurements on poly(ethylene
      terephthalate), poly(vinylidene fluoride), Nylon-66,
      poly(chlorotrifluoroethylene) (PCTFE), and the polymer gel system
      poly(acrylonitrile)-ethylene carbonate-propylene carbonate are evaluated within
      the A4 scenario of the MCT. For all these systems, very good agreement is found
      between the theoretical and experimental spectra. The data analysis is
      demonstrated to be facilitated considerably by plotting the data in the complex
      plane whereby the elliptic functions derived from the theory for the frequency
      dependent dielectric function can be replaced by polynomials. For PCTFE, the
      scaling behavior predicted by the MCT could be verified and the temperature
      dependences of the extracted scaling parameters were found to be consistent with
      theory.

PMID- 11461279
TI  - Slow dynamics near glass transitions in thin polymer films.
AB  - The alpha process (segmental motion) of thin polystyrene films supported on glass
      substrate has been investigated in a wider frequency range from 10(-3) Hz to
      10(4) Hz using dielectric relaxation spectroscopy and thermal expansion
      spectroscopy. The relaxation rate of the alpha process increases with decreasing
      film thickness at a given temperature above the glass transition. This increase
      in the relaxation rate with decreasing film thickness is much more enhanced near
      the glass transition temperature. The glass transition temperature determined as
      the temperature at which the relaxation time of the alpha process becomes a
      macroscopic time scale shows a distinct molecular weight dependence. It is also
      found that the Vogel temperature has a thickness dependence, i.e., the Vogel
      temperature decreases with decreasing film thickness. The expansion coefficient
      of the free volume alpha(f) is extracted from the temperature dependence of the
      relaxation time within the free volume theory. The fragility index m is also
      evaluated as a function of thickness. Both alpha(f) and m are found to decrease
      with decreasing film thickness.

PMID- 11461280
TI  - Counterion correlations and attraction between like-charged macromolecules.
AB  - A simple model is presented for the appearance of attraction between two like
      charged polyions inside a polyelectrolyte solution. The polyions are modeled as
      rigid cylinders in a continuum dielectric solvent. The strong electrostatic
      interaction between the polyions and the counterions results in counterion
      condensation. If the two polyions are sufficiently close to each other their
      layers of condensed counterions can become correlated resulting in attraction
      between the macromolecules. To explore the counterion induced attraction we
      calculate the correlation functions for the condensed counterions. It is found
      that the correlations are of very short range. For the parameters specific to the
      double stranded DNA, the correlations and the attraction appear only when the
      surface-to-surface separation is less than 7 A.

PMID- 11461281
TI  - Single homopolymers in the relative density representation.
AB  - A single symmetric homopolymer is studied in the grand ensemble of its monomeric
      units. For an arbitrary external field but next neighbor interactions alone, such
      a system is represented as a functional of the local density to local fugacity
      ratio, conjugate to the fugacity, with the excess grand potential as
      thermodynamic generating function. A sample case in a spherical enclosure is
      solved, where a complementary exclusion from a spherical volume requires an
      extension to a grand ensemble of polymers. A preliminary extension is also made
      in mean field form to non-neighbor interactions, as well as to nonsymmetric
      interactions.

PMID- 11461282
TI  - Effects of random migration in population dynamics.
AB  - We study the influence of random migration of a species (may be insects) in the
      population dynamics when initially all the individuals live in a primordial site
      (their habitats may be trees). We assume (i) a finite number of sites, (ii) that
      migration occurs randomly to nearest neighbors, and (iii) an on-site age
      structured population whose size varies according to Ricker's map. We find that
      even for a very small migration rate, the population density becomes appreciably
      affected. If migration is not allowed, depending on the value of the
      characteristic parameters, the population may display a chaotic oscillation;
      however, with migration permitted, the chaos is reduced or even suppressed, and
      the population density will oscillate with period 2 or period 4. We examined the
      effects of migration through higher-order iterations of the map, entropy, and
      time correlation function. We also considered a long chain, analyzing (a) the
      spatial correlation between sites, noting the occurrence of a transition in the
      correlation function between sites separated by odd and even units of distance
      and (b) the fluctuations in time of the populations when initially all sites are
      populated.

PMID- 11461283
TI  - Active and passive particles: modeling beads in a bacterial bath.
AB  - A simple model for the motion of passive particles in a bath of active, self
      propelled ones is introduced. It is argued that this approach provides the
      correct framework within which to cast the recent experimental results obtained
      by Wu and Libchaber [Phys Rev. Lett. 84, 3017 (2000)] for the diffusive
      properties of polystyrene beads displaced by bacteria suspended in a two
      dimensional fluid film. Our results suggest that superdiffusive behavior should
      indeed be generically observed in the transition region marking the onset of
      collective motion.

PMID- 11461284
TI  - Adhesion-induced phase behavior of multicomponent membranes.
AB  - Biomimetic membranes that contain several molecular components are studied
      theoretically. In contact with another surface, such as a solid substrate or
      another membrane, some of these intramembrane components are attracted by the
      second surface and, thus, act as local stickers. The cooperative behavior of
      these systems is characterized by the interplay of (i) attractive binding
      energies, (ii) entropic contributions arising from the shape fluctuations of the
      membranes, and (iii) the entropy of mixing of the stickers. A systematic study of
      this interplay, which starts from the corresponding partition functions, reveals
      that there are several distinct mechanisms for adhesion-induced phase separation
      within the membranes. The first of these mechanisms is effective for flexible
      stickers with attractive cis interactions (within the same membrane) and arises
      from the renormalization of these interactions by the confined membrane
      fluctuations. A second, purely entropic mechanism is found for rigid stickers
      without attractive cis interactions and arises from a fluctuation-induced line
      tension. Finally, a third mechanism is present if the membrane contains both
      stickers and repellers, i.e., nonadhesive molecules that protrude from the
      membrane surface. This third mechanism is based on an effective potential barrier
      and becomes less effective if the shape fluctuations of the membrane become more
      pronounced.

PMID- 11461285
TI  - Designability of lattice model heteropolymers.
AB  - Protein folds are highly designable, in the sense that many sequences fold to the
      same conformation. In the present work we derive an expression for the
      designability in a 20-letter lattice model of proteins which, relying only on the
      central limit theorem, has a generality which goes beyond the simple model used
      in its derivation. This expression displays an exponential dependence on the
      energy of the optimal sequence folding on the given conformation measured with
      respect to the lowest energy of the conformational dissimilar structures, an
      energy difference which constitutes the only parameter controlling designability.
      Accordingly, the designability of a native conformation is intimately connected
      to the stability of the sequences folding to them.

PMID- 11461286
TI  - Constructive role of noise in signal transmissions by biomembrane proteins.
AB  - We discuss new examples of the constructive role of environmental fluctuations in
      biophysical processes, namely quantitative enhancement and qualitative sharpening
      of the outgoing signal in the intercellular signal transduction, e.g., in the
      synaptic links. An experimental check in a chemical flow reactor is suggested.

PMID- 11461287
TI  - Modeling translocation of particles on one-dimensional polymer lattices.
AB  - We introduce a general random walk model that is an extension of the random walk
      model proposed by Berg. The model can be used to describe a particle's
      translocation along a polymeric lattice with a nonuniform distribution of
      obstacles. These obstacles are representative of DNA-bound proteins, of drugs,
      and of a DNA packing environment. Using this model in the bacteriophage
      replication process, we show the effects of random obstacles on an ATP-driven
      particle's translocation along single-stranded DNA. The principal finding is that
      the average statistical time of the translocation process decreases with the
      increase of an obstacle's strength. We also find an interesting relation between
      the average statistical time and the DNA chain length. Our results can be used to
      explain some physiological phenomena. They show the usefulness of our model in an
      analysis of the effect of random obstacles on particles' translocation along one
      dimensional polymer lattices.

PMID- 11461288
TI  - Conformational dynamics of an alanine dipeptide analog: an ab initio molecular
      dynamics study.
AB  - An ab initio molecular dynamics (MD) simulation technique employing the Born
      Oppenheimer approach in the framework of a Gaussian implementation of Kohn-Sham
      density functional theory is used to study the gas-phase conformational dynamics
      of an alanine dipeptide analog. It is found that conformational transformation
      between C5 and C7(eq) occurs on the picosecond time scale. Classical MD
      simulations using most of the popular force fields do not yield a transition even
      after nanoseconds. An analysis is given of the difference, for this small gas
      phase system, between ab initio MD and traditional MD simulation using force
      fields.

PMID- 11461289
TI  - Architecture of idiotypic networks: percolation and scaling behavior.
AB  - We investigate a model where idiotypes (characterizing B lymphocytes and
      antibodies of an immune system) and anti-idiotypes are represented by
      complementary bit strings of a given length d allowing for a number of mismatches
      (matching rules). In this model, the vertices of the hypercube in dimension d
      represent the potential repertoire of idiotypes. A random set of (with
      probability p) occupied vertices corresponds to the expressed repertoire of
      idiotypes at a given moment. Vertices of this set linked by the above matching
      rules build random clusters. We give a structural and statistical
      characterization of these clusters, or in other words of the architecture of the
      idiotypic network. Increasing the probability p one finds at a critical p a
      percolation transition where for the first time a large connected graph occurs
      with probability 1. Increasing p further, there is a second transition above
      which the repertoire is complete in the sense that any newly introduced idiotype
      finds a complementary anti-idiotype. We introduce structural characteristics such
      as the mass distribution and the fragmentation rate for random clusters, and
      determine the scaling behavior of the cluster size distribution near the
      percolation transition, including finite size corrections. We find that slightly
      above the percolation transition the large connected cluster (the central part of
      the idiotypic network) consists typically of one highly connected part and a
      number of weakly connected constituents and coexists with a number of small,
      isolated clusters. This is in accordance with the picture of a central and a
      peripheral part of the idiotypic network and gives some support to idealized
      architectures of the central part used in recent dynamical mean field models.

PMID- 11461290
TI  - Fluctuating elastic rings: statics and dynamics.
AB  - We study the effects of thermal fluctuations on elastic rings. Analytical
      expressions are derived for correlation functions of Euler angles, mean-square
      distance between points on the ring contour, radius of gyration, and probability
      distribution of writhe fluctuations. Since fluctuation amplitudes diverge in the
      limit of vanishing twist rigidity, twist elasticity is essential for the
      description of fluctuating rings. We discover a crossover from a small scale
      regime in which the filament behaves as a straight rod, to a large scale regime
      in which spontaneous curvature is important and twist rigidity affects the
      spatial configurations of the ring. The fluctuation-dissipation relation between
      correlation functions of Euler angles and response functions, is used to study
      the deformation of the ring by external forces. The effects of inertia and
      dissipation on the relaxation of temporal correlations of writhe fluctuations,
      are analyzed using Langevin dynamics.

PMID- 11461291
TI  - Influence of environment fluctuations on incoherent neutron scattering functions.
AB  - In extending the conventional dynamic models, we consider a simple model to
      account for the environment fluctuations of particle atoms in a protein system
      and derive the elastic incoherent structure factor (EISF) and the incoherent
      scattering correlation function C(Q,t) for both the jump dynamics between sites
      with fluctuating site interspacing and for the diffusion inside a fluctuating
      sphere. We find that the EISF of the system (or the normalized elastic intensity)
      is equal to that in the absence of fluctuations averaged over the distribution of
      site interspacing or sphere radius a. The scattering correlation function is
      C(Q,t)= Sigma(n)<e(-lambda(n)(a)t)> psi(t), where the average is taken over the Q
      dependent effective distribution of relaxation rates lambda(n)(a), and psi(t) is
      the correlation function of the length a. When psi(t)=1, the relaxation of C(Q,t)
      is exponential for the jump dynamics between sites [since lambda(n)(a) is
      independent of a] while it is nonexponential for diffusion inside a sphere.

PMID- 11461292
TI  - Electrohydrodynamic instability of a charged membrane.
AB  - The stability of shape fluctuations of a flat charged membrane immersed in a
      fluid is analyzed using a linear stability analysis. A displacement of the
      membrane surface causes a fluctuation in the conterion density at the surface.
      This in turn causes an additional contribution to the force density in the
      momentum equation for the fluid, which results in a normal stress at the surface
      which is opposite in direction to the stress caused by surface tension. This
      electrohydrodynamic effect destabilizes fluctuations when the surface potential
      exceeds a critical value.

PMID- 11461293
TI  - Folding simulations of a three-dimensional protein model with a nonspecific
      hydrophobic energy function.
AB  - We show that a nonspecific hydrophobic energy function can produce protein-like
      folding behavior of a three-dimensional protein model of 40 monomers in the cubic
      lattice when the native conformation is chosen judiciously. We confirm that
      monomer inside/outside segregation is a powerful criterion for the selection of
      appropriate structures, an idea that was recently proposed with basis on a
      general theoretical analysis and simulations of much simpler two-dimensional
      models.

PMID- 11461294
TI  - Self-consistent simulations of electroporation dynamics in biological cells
      subjected to ultrashort electrical pulses.
AB  - The temporal dynamics of electroporation of cells subjected to ultrashort voltage
      pulses are studied based on a coupled scheme involving the Laplace, Nernst-Plank,
      and Smoluchowski equations. A pore radius dependent energy barrier for ionic
      transport, accounts for cellular variations. It is shown that a finite time delay
      exists in pore formation, and leads to a transient overshoot of the transmembrane
      potential V(mem) beyond 1.0 V. Pore resealing is shown to consist of an initial
      fast process, a 10(-4) s delay, followed by a much slower closing at a time
      constant of about 10(-1) s. This establishes a time-window during which the pores
      are mostly open, and hence, the system is most vulnerable to destruction by a
      second electric pulse. The existence of such a time window for effective killing
      by a second pulse is amply supported by our experimental data for E. coli cells.
      The time constant for the longer process also matches experiments. The study
      suggests that controlled manipulation of the pore "open times" can be achieved
      through multiple, ultrashort pulses.

PMID- 11461295
TI  - Mechanisms for facilitated target location and the optimal number of molecules in
      the diffusion search process.
AB  - We investigate the number N of molecules needed to perform independent diffusion
      in order to achieve bonding of a single molecule to a specific site in time t(0).
      For a certain range of values of t(0), an increase from N to kN molecules (k>1)
      results in the decrease of search time from t(0) to t(0)/k. In this regime,
      increasing the number of molecules is an effective way of speeding up the search
      process. However when N> or =N0 (optimal number of N) the reduction of time from
      t(0) to t(0)/k can be achieved only by an exponentially large increase in the
      number of molecules [from N to N exp(ck) for some c>0].

PMID- 11461296
TI  - Optimal colored perceptrons.
AB  - Ashkin-Teller type perceptron models are introduced. Their maximal capacity per
      number of couplings is calculated within a first-step replica-symmetry-breaking
      Gardner approach. The results are compared with extensive numerical simulations
      using several algorithms.

PMID- 11461297
TI  - Influence of shear flow on vesicles near a wall: A numerical study.
AB  - We describe the dynamics of three-dimensional fluid vesicles in steady shear flow
      in the vicinity of a wall. This is analyzed numerically at low Reynolds numbers
      using a boundary element method. The area-incompressible vesicle exhibits bending
      elasticity. Forces due to adhesion or gravity oppose the hydrodynamic lift force
      driving the vesicle away from a wall. We investigate three cases. First, a
      neutrally buoyant vesicle is placed in the vicinity of a wall that acts only as a
      geometrical constraint. We find that the lift velocity is linearly proportional
      to shear rate and decreases with increasing distance between the vesicle and the
      wall. Second, with a vesicle filled with a denser fluid, we find a stationary
      hovering state. We present an estimate of the viscous lift force that seems to
      agree with recent experiments of Lorz et al. [Europhys. Lett. 51, 468 (2000)].
      Third, if the wall exerts an additional adhesive force, we investigate the
      dynamical unbinding transition that occurs at an adhesion strength linearly
      proportional to the shear rate.

PMID- 11461298
TI  - Toward a theory of the general-anesthetic-induced phase transition of the
      cerebral cortex. I. A thermodynamics analogy.
AB  - In a recent paper the authors developed a stochastic model for the response of
      the cerebral cortex to a general anesthetic agent. The model predicted that there
      would be an anesthetic-induced phase change at the point of transition into
      unconsciousness, manifested as a divergence in the electroencephalogram spectral
      power, and a change in spectral energy distribution from being relatively
      broadband in the conscious state to being strongly biased towards much lower
      frequencies in the unconscious state. Both predictions have been verified in
      recent clinical measurements. In the present paper we extend the model by
      calculating the equilibrium distribution function for the cortex, allowing us to
      establish a correspondence between the cortical phase transition and the more
      familiar thermodynamic phase transitions. This correspondence is achieved by
      first identifying a cortical free energy function, then by postulating that there
      exists an inverse relationship between an anesthetic effect and a quantity we
      define as cortical excitability, which plays a role analogous to temperature in
      thermodynamic phase transitions. We follow standard thermodynamic theory to
      compute a cortical entropy and a cortical "heat capacity," and we investigate how
      these will vary with anesthetic concentration. The significant result is the
      prediction that the entropy will decrease discontinuously at the moment of
      induction into unconsciousness, concomitant with a release of "latent heat" which
      should manifest as a divergence in the analogous heat capacity. There is clear
      clinical evidence of heat capacity divergence in historical anesthetic-effect
      measurements performed in 1977 by Stullken et al. [Anesthesiology 46, 28 (1977)].
      The discontinuous step change in cortical entropy suggests that the cortical
      phase transition is analogous to a first-order thermodynamic transition in which
      the comatose-quiescent state is strongly ordered, while the active cortical state
      is relatively disordered.

PMID- 11461299
TI  - Toward a theory of the general-anesthetic-induced phase transition of the
      cerebral cortex. II. Numerical simulations, spectral entropy, and correlation
      times.
AB  - In our two recent papers [M.L. Steyn-Ross et al., Phys. Rev. E 60, 7299 (1999);
      64, 011917 (2001)] we presented clinical evidence for a general anesthetic
      induced phase change in the cerebral cortex, and showed how the significant
      features of the cortical phase change (biphasic power surge, spectral energy
      redistribution, "heat capacity" divergence), could be explained using a
      stochastic single-macrocolumn model of the cortex. The model predictions were
      based on rather strong "adiabatic" assumptions which assert that the mean-field
      excitatory and inhibitory macrocolumn voltages are "slow" variables whose
      equilibration times are much longer than those of the input "currents" that drive
      the macrocolumn. In the present paper we test the adiabatic assumption by running
      numerical simulations of the stochastic differential equations. These simulations
      confirm the number and nature of the steady-state solutions, the growth of
      fluctuation power at transition, and the redistribution of spectral energy
      towards lower frequencies. We use spectral entropy to quantify these changes in
      the power spectral density, and to show that the spectral entropy should decrease
      markedly at the point of transition. This prediction agrees with recent clinical
      findings by Viertio-Oja and colleagues [J. Clinical Monitoring Computing 16, 60
      (2000)]. Our modeling work shows that there is an inverse relationship between
      spectral entropy H and correlation time T of the soma-voltage fluctuations: H
      inversely proportional to (ln T). In a theoretical analysis we prove that this
      proportionality becomes exact for an ideal Lorentzian process. These findings
      suggest that by monitoring the changes in EEG correlation time, it should be
      possible to track changes in the state of patient consciousness.

PMID- 11461300
TI  - Noise, regularizers, and unrealizable scenarios in online learning from
      restricted training sets.
AB  - We study the dynamics of online learning in multilayer neural networks where
      training examples are sampled with repetition and where the number of examples
      scales with the number of network weights. The analysis is carried out using the
      dynamical replica method aimed at obtaining a closed set of coupled equations for
      a set of macroscopic variables from which both training and generalization errors
      can be calculated. We focus on scenarios whereby training examples are corrupted
      by additive Gaussian output noise and regularizers are introduced to improve the
      network performance. The dependence of the dynamics on the noise level, with and
      without regularizers, is examined, as well as that of the asymptotic values
      obtained for both training and generalization errors. We also demonstrate the
      ability of the method to approximate the learning dynamics in structurally
      unrealizable scenarios. The theoretical results show good agreement with those
      obtained from computer simulations.

PMID- 11461301
TI  - Observations and modeling of synchronized bursting in two-dimensional neural
      networks.
AB  - We present long-term (approximately hours) measurements of the spontaneous
      activity of two-dimensional cortical cell neural networks placed on
      multielectrode arrays. We compare histograms of single neuron interspike
      intervals and the network intersynchronized bursting events intervals. In
      addition, the effect of Ca concentration on the network activity is being
      studied. At 1 mM Ca concentration, the network exhibits periodic synchronized
      bursting that fades away after about 20 min. We present a feedback-regulated
      integrate and fire model to account for the observations. In the model we include
      two additional features: dynamical threshold and synapse fatigue.

PMID- 11461302
TI  - Resonant activation in a system with deterministic oscillations of barrier
      height.
AB  - A thermally relaxing system with a harmonically oscillating barrier height is
      considered. The dynamics of the system are described by a Smoluchowski equation
      with a time dependent right hand side. For both absorbing and reflecting boundary
      conditions, the solutions of this equation show that the oscillating system has
      the same resonant properties, and the same dependence on initial conditions,
      respectively, on the phase of the harmonic oscillations, as a conventional
      resonant system in which the barrier executes dichotomic Markovian fluctuations.

PMID- 11461303
TI  - Interface fluctuations under shear.
AB  - Coarsening systems under uniform shear display a long time regime characterized
      by the presence of highly stretched and thin domains. The question then arises
      whether thermal fluctuations may actually destroy this layered structure. To
      address this problem in the case of nonconserved dynamics, we study an
      anisotropic version of the Burgers equation, constructed to describe thermal
      fluctuations of an interface in the presence of a uniform shear flow. As a
      result, we find that stretched domains are only marginally stable against thermal
      fluctuations in d=2, whereas they are stable in d=3.

PMID- 11461304
TI  - Compressibility sum rule for the two-dimensional electron gas.
AB  - The authors establish formulas for the isothermal compressibility and long
      wavelength static density-density response function of a weakly correlated two
      dimensional electron gas in the 1<<beta epsilon(F)<infinity and 0< or =beta
      epsilon(F)<<1 degeneracy domains; beta epsilon(F)=pi n Planck's over 2
      pi(2)/(mk(B)T). The calculation of the pressure in the former domain is based on
      the Isihara-Toyoda formula [A. Isihara and T. Toyoda, Phys. Rev. B 21, 3358
      (1980)] for the exchange-correlation energy at finite temperature. The pressure
      calculation in the latter domain is based on the Totsuji classical cluster
      expansion formula for the correlation energy [H. Totsuji, J. Phys. Soc. Jpn. 40,
      857 (1976); Phys. Rev. A 19, 889 (1979)].

PMID- 11461305
TI  - Trace formula for noise corrections to trace formulas.
AB  - We consider an evolution operator for a discrete Langevin equation with a
      strongly hyperbolic classical dynamics and Gaussian noise. Using an integral
      representation of the evolution operator L, we investigate the high-order
      corrections to the trace of L(n). The asymptotic behavior is found to be
      controlled by subdominant saddle points previously neglected in the perturbative
      expansion. We show that a trace formula can be derived to describe the high-order
      noise corrections.

PMID- 11461306
TI  - Superballistic spreading of wave packets.
AB  - We demonstrate for various systems that the variance of a wave packet M(t)
      proportional to t(nu), can show a superballistic increase with 2 < nu < or = 3,
      for parametrically large time intervals. A model is constructed that explains
      this phenomenon and its predictions are verified numerically for various
      disordered and quasiperiodic systems.

PMID- 11461307
TI  - Entropically driven ordering in a binary colloidal suspension near a planar wall.
AB  - The local ordering of a binary hard-sphere mixture with a size ratio 1:10 near a
      planar wall is investigated by means of integral equation theory. We find that
      when the bulk volume fraction of the smaller particles is greater than 15%, the
      larger particles (at a bulk volume fraction of 1% and higher) become highly
      localized on the wall surface, forming a quasi-two-dimensional surface-localized
      monolayer. Our results are discussed and compared against computer simulation
      data with an effective one-component Hamiltonian that is based on sphere-sphere
      and sphere-wall depletion potentials.

PMID- 11461308
TI  - Reentrant miscibility in fluids with spherical interactions.
AB  - We have obtained the closed-loop fluid-fluid immiscibility in the phase diagram
      of a binary mixture with interactions with spherical symmetry. That topology
      appears when a short-range attractive interaction is considered between unlike
      pair molecules. We present "exact" results obtained from Monte Carlo simulation
      on different ensembles and results from the application of a first-order
      perturbation theory.

PMID- 11461309
TI  - Temperature dependence of the refractive index near the reentrant-isotropic-
      calamitic-nematic phase transition.
AB  - The laser-induced nonlinear optical response of a lyotropic liquid crystal system
      in the reentrant-isotropic and calamitic-nematic phases is investigated by the
      use of the thermal lens technique. The occurrence of an inversion in the
      temperature coefficient of the ordinary refractive index, dn(radially)/dT, near
      the reentrant-isotropic-calamitic-nematic phase transition, is discussed. This
      effect is attributed to the behavior of the electronic polarizability due to the
      change in micelle shape near the isotropic-nematic transition, and correlated
      with the results obtained near the nematic-isotropic transition, previously
      reported.

PMID- 11461310
TI  - Simulations on the number of entanglements of a polymer network using knot
      theory.
AB  - Polymer networks, created on the computer using the Bond-Fluctuation-Algorithm,
      offer the possibility to count the number of entanglements. We generated networks
      consisting of 5000 chains that were cross linked at their end groups via tetra
      functional cross linkers. The analysis of the topology was performed by computing
      the Homfly polynomial of the entanglements offering a much more precise
      determination of the knot and entanglement type than the Gaussian linking number.
      It also allows us to determine the influence of Brunnian links. Results
      concerning the connection between the chain length and the number of
      entanglements are shown.

PMID- 11461311
TI  - Information transmission and recovery in neural communication channels revisited.
AB  - Nerve cells in the brain generate all-or-none electric events-spikes-that are
      transmitted to other nerve cells via chemical synapses. An important issue in
      neuroscience is how neurons encode and transmit information using spike trains.
      Recently, signal transduction through two neurons connected by an excitatory
      chemical synapse was studied by Eguia et al. [Phys. Rev. E 62, 7111 (2000)]. They
      reported an apparent violation of the data processing inequality: The mutual
      information between the input signal and the output of the first neuron can be
      lower than the mutual information between the input signal and the output of the
      second neuron, that only receives input from the first neuron. We investigate
      whether it is possible, using a different method, to retrieve, from the first
      neuron's spike train, all the information about the input that is present in the
      second neuron's output. We find that single interspike intervals (ISI's) from the
      first neuron, at a resolution of 0.5 time units, contain more information about
      the input signal than those of the second neuron. Using a classification
      procedure based on the ISI return map, we recover 71% of the input entropy using
      the first neuron's spike train, and only 42% using the second neuron's spike
      train. Hence for these spike-train observables the data processing inequality is
      not violated.

PMID- 11461312
TI  - Enhanced phase synchrony in the electroencephalograph gamma band for musicians
      while listening to music.
AB  - Multichannel electroencephalograph signals from two broad groups, 10 musicians
      and 10 nonmusicians, recorded in different states (in resting states or no task
      condition, with eyes opened and eyes closed, and with two musical tasks,
      listening to two different pieces of music) were studied. Degrees of phase
      synchrony in various frequency bands were assessed. No differences in the degree
      of synchronization in any frequency band were found between the two groups in
      resting conditions. Yet, while listening to music, significant increases of
      synchronization were found only in the gamma-frequency range (>30 Hz) over large
      cortical areas for the group of musicians. This high degree of synchronization
      elicited by music in the group of musicians might be due to their ability to host
      long-term memory representations of music and mediate access to these stored
      representations.

PMID- 11461313
TI  - First-principle approach to dielectric behavior of nonspherical cell suspensions.
AB  - We present a theoretical study of the dielectric behavior of cell suspensions by
      employing the Bergman-Milton spectral representation of the effective dielectric
      constant. By means of the spectral representation, we derive the dielectric
      dispersion spectrum in terms of the electrical and structure parameters of the
      cell models. Our results show that a better agreement with the experimental data
      can be obtained, provided that we introduce a conductivity contrast
      t=sigma(2)/(sigma(2)-sigma(1)). We find that the conductivity of the cell
      cytoplasm sigma(1) can be much larger than that of the suspending medium
      sigma(2), in contrast to the previous claim that sigma(1) approximately sigma(2).

PMID- 11461314
TI  - Comment on "Long-range electrostatic interactions between like-charged colloids:
      Steric and confinement effects".
AB  - In a recent study [Phys. Rev. E 60, 6530 (1999)], Trizac and Raimbault showed
      that the effective pair interaction between like-charged colloids immersed in a
      cylindrically confined electrolyte remains repulsive even when the size of the
      microions and the finite longitudinal extension of the confining cylinder are
      taken into account. Contrary to their claim, we argue that the case of finite
      longitudinal confinement does not always generate repulsive interactions and to
      illustrate this point we also provide a simple example.

PMID- 11461315
TI  - Persistence of a continuous stochastic process with discrete-time sampling.
AB  - We introduce the concept of "discrete-time persistence," which deals with zero
      crossings of a continuous stochastic process, X(T), measured at discrete times,
      T=n Delta T. For a Gaussian Markov process with relaxation rate mu, we show that
      the persistence (no crossing) probability decays as [rho(a)](n) for large n,
      where a = exp(-mu Delta T), and we compute rho(a) to high precision. We also
      define the concept of "alternating persistence," which corresponds to a<0. For
      a>1, corresponding to motion in an unstable potential (mu<0), there is a nonzero
      probability of having no zero-crossings in infinite time, and we show how to
      calculate it.

PMID- 11461316
TI  - Is memory in the minority game irrelevant?
AB  - By analyzing the frequencies of selecting entries in the strategies and time
      series data of the minority game, we show that the memory in the minority game is
      irrelevant for the emergence of coordinate behavior. It is found that the memory
      in the game just yields periodic structures and statistically does not play any
      significant role as far as the volatility is concerned.

PMID- 11461317
TI  - Noise-resistant chaotic synchronization.
AB  - The practical applications of self-synchronizing chaotic systems are greatly
      limited by their sensitivity to noise. Even small amounts of noise added to the
      synchronizing signal can degrade synchronization to the point where information
      encoded on the chaotic signal can't be recovered. In this paper, I show that it
      is possible to build chaotic circuits that operate on two different time scales.
      The separation of time scales allows the low frequency part of the circuit to
      average out noise added to the synchronizing signal. Adjusting the relative time
      scales of the two parts of the circuit allow one to make the synchronization
      error arbitrarily close to the error caused by circuit mismatch for any amount of
      added noise.

PMID- 11461318
TI  - Shape of analyticity domains of Lindstedt series: the standard map.
AB  - The analyticity domains of the Lindstedt series for the standard map are studied
      numerically using Pade approximants to model their natural boundaries. We show
      that if the rotation number is a Diophantine number close to a rational value
      p/q, then the radius of convergence of the Lindstedt series becomes smaller than
      the critical threshold for the corresponding Kol'mogorov-Arnol'd-Moser curve, and
      the natural boundary on the plane of the complexified perturbative parameter
      acquires a flower-like shape with 2q petals.

PMID- 11461319
TI  - Targeting spatiotemporal patterns in extended systems with multiple coexisting
      attractors.
AB  - We set up adaptive control algorithms which can be used to achieve control to
      desired attractors in spatially extended systems. Traditional adaptive control
      methods often fail in such systems due to the presence of multiple coexisting
      attractors that lead to a high probability of the system getting trapped in an
      undesired attractor despite the application of control. We use quenching
      techniques to achieve control in such difficult scenarios. When the control
      parameter evolves through parameter regions that lead to undesired attractors,
      the control parameter is changed sufficiently fast so that the system does not
      get time to get trapped in these attractors, but gets quenched instead to the
      desirable attractor. The rate of change of the parameter is guided by using
      variable stiffness of control. We demonstrate the efficacy of our technique in a
      system of coupled sine-circle maps. Further, such variable stiffness schemes can
      also be used to step up the efficiency of adaptive control algorithms by making
      frequent suitable changes in the stiffness of control during the control
      dynamics. This strategy is very successful in reducing the time required to
      achieve control, while maintaining the stability of the control dynamics.

PMID- 11461320
TI  - Asymptotic quantum behavior of classically anomalous maps.
AB  - In the framework of quantum chaos, the theory of dynamical localization plays an
      outstanding role, both for its conceptual relevance and physical import.
      Theoretical arguments, confirmed by a large amount of numerical simulations, have
      shown in the case of complete classical chaos, that the localization length is
      related to the classical diffusion constant and the effective Planck's constant
      Planck's over 2 pi. We investigate the quantum behavior when classical dynamics
      exhibits anomalous diffusion (so that the diffusion constant is not defined): we
      show that dynamical localization still takes place, and that the scaling with the
      quantum parameter is the same as the classically diffusive case.

PMID- 11461321
TI  - Internal symmetry in the multifractal spectrum of fully developed turbulence.
AB  - In the context of multifractal theory and She-Leveque's model describing the
      statistics of intermittency in fully developed turbulence, we show that the
      multifractal dimensions can be simply written F(alpha)=1+alpha*
      alpha*ln(alpha*/2) with alpha*=(2 beta-1-alpha)/ln beta=2 beta(p), where p is the
      order associated to the moment <epsilon(p)(r)> (with p> or =0) based on the rate
      of energy dissipation epsilon(r) and beta=[(1+3/the square root of 8)(1/3)+(1
      3/the square root of 8)(1/3](3) approximately equal to 0.68). Introducing the
      fractal dimensions Delta(p)=F(alpha)+alpha*ln(alpha*/2), this leads to the
      recursive relation beta=(Delta(p+1)-Delta(infinity))/(Delta(p)-Delta(infinity))
      with Delta(infinity)=1. This suggests the existence of an internal symmetry in
      the multifractal spectrum of fully developed turbulence, which reduces
      considerably the number of parameters necessary to characterize intermittency
      statistics.

PMID- 11461322
TI  - Maximum-J capability in a quasiaxisymmetric stellarator.
AB  - Maximum-J (J is the second adiabatic invariant) capability, i.e., the radial
      derivative of J has the same sign as that of pressure, is investigated in a
      quasiaxisymmetric (QA) stellarator to investigate improved confinement. Due to
      the existence of nonaxisymmetry of the magnetic field strength, a local maximum
      of J is created to cause the drift reversal. External controllability of the
      maximum-J condition is also demonstrated, by which the impact of magnetic
      configuration on turbulent transport can be studied.

PMID- 11461323
TI  - High-energy electron beam production by femtosecond laser interactions with
      exploding-foil plasmas.
AB  - The interaction of an ultraintense, 30-fs laser pulse with a preformed plasma was
      investigated as a method of producing a beam of high-energy electrons. We used
      thin foil targets that are exploded by the laser amplified spontaneous emission
      preceding the main pulse. Optical diagnostics show that the main pulse interacts
      with a plasma whose density is well below the critical density. By varying the
      foil thickness, we were able to obtain a substantial emission of electrons in a
      narrow cone along the laser direction with a typical energy well above the laser
      ponderomotive potential. These results are explained in terms of wake-field
      acceleration.

PMID- 11461324
TI  - Defects and particle motions in the nonuniform melting of a two-dimensional
      Coulomb cluster.
AB  - The defect excitation and nonuniform melting of a two-dimensional Coulomb cluster
      with 300 charged particles (interacting with 1/r type force) in a uniform
      neutralizing background are studied numerically. Intrinsic defects exist around
      the outer circular shells surrounding the inner triangular lattice. They are the
      source regions for anisotropic particle thermal vibrations and then cyclic
      hoppings with the increasing temperature. It leads to the nonuniform melting
      associated with the thermal motion of intrinsic defects, and then the thermal
      excitation of dislocation pairs and disclinations. The intrinsic defect free
      center core has the highest melting temperature. It shows the sequential losses
      of translational and then orientational orders.

PMID- 11461325
TI  - Metastable states in glassy systems.
AB  - Truly stable metastable states are an artifact of the mean-field approximation or
      the zero-temperature limit. If such appealing concepts in glass theory as
      configurational entropy are to have a meaning beyond these approximations, one
      needs to cast them in a form involving states with finite lifetimes. Starting
      from elementary examples and using the results of Gaveau and Schulman, we propose
      a simple expression for the configurational entropy and revisit the question of
      taking flat averages over metastable states. The construction is applicable to
      finite-dimensional systems, and we explicitly show that for simple mean-field
      glass models it recovers, justifies, and generalizes the known results. The
      calculation emphasises the appearance of new dynamical order parameters.

PMID- 11461326
TI  - Statistics of atmospheric correlations.
AB  - For a large class of quantum systems, the statistical properties of their
      spectrum show remarkable agreement with random matrix predictions. Recent
      advances show that the scope of random matrix theory is much wider. In this work,
      we show that the random matrix approach can be beneficially applied to a
      completely different classical domain, namely, to the empirical correlation
      matrices obtained from the analysis of the basic atmospheric parameters that
      characterize the state of atmosphere. We show that the spectrum of atmospheric
      correlation matrices satisfy the random matrix prescription. In particular, the
      eigenmodes of the atmospheric empirical correlation matrices that have physical
      significance are marked by deviations from the eigenvector distribution.

PMID- 11461327
TI  - Model of correlated sequential adsorption of colloidal particles.
AB  - We present results of a model of sequential adsorption in which the adsorbing
      particles are correlated with the particles attached to the substrate. The
      strength of the correlations is measured by a tunable parameter sigma. The model
      interpolates between free ballistic adsorption in the limit sigma-->infinity and
      a strongly correlated phase, appearing for sigma-->0 and characterized by the
      emergence of highly ordered structures. The phenomenon is manifested through the
      analysis of several magnitudes, as the jamming limit and the particle-particle
      correlation function. The effect of correlations in one dimension manifests in
      the increased tendency to particle chaining in the substrate. In two dimensions
      the correlations induce a percolation transition, in which a spanning cluster of
      connected particles appears at a certain critical value sigma(c). Our study could
      be applicable to more general situations in which the coupling between
      correlations and disorder is relevant, as for example, in the presence of strong
      interparticle interactions.

PMID- 11461328
TI  - Critical behavior of a nonequilibrium system with two nonordering conserved
      fields.
AB  - We investigate the critical behavior of a nonequilibrium system with two particle
      species A and B that exhibits a continuous absorbing-state phase transition. The
      number of particles of each species (N(A) and N(B)) is conserved by the dynamical
      process. Numerical results show that the order parameter exponent beta depends on
      the ratio N(B)/N(A) at criticality. Some aspects of critical dynamic behavior are
      also studied, namely, the decay of the active density at criticality and the
      critical spreading of a perturbation to an absorbing configuration. Anomalies in
      the relaxation are associated with the presence of different time scales in the
      dynamics of the model.

PMID- 11461329
TI  - Molecular dynamics simulations of spin and pure liquids with preservation of all
      the conservation laws.
AB  - A methodology is developed to integrate numerically the equations of motion for
      classical many-body systems in molecular dynamics simulations. Its
      distinguishable feature is the possibility to preserve, independently on the size
      of the time step, all the conservation laws inherent in the description without
      breaking the time reversibility. As a result, an implicit second-order algorithm
      is derived and applied to pure liquids, as well as spin liquids, for which the
      dynamics is characterized by the conservation of total energy, linear and angular
      momenta, as well as magnetization and individual spin lengths. It is demonstrated
      on the basis of Lennard-Jones and Heisenberg fluid models that when such
      quantities as energy and magnetization must be conserved perfectly, the algorithm
      turns out to be more efficient than popular decomposition integrators and
      standard predictor-corrector schemes.

PMID- 11461330
TI  - Enhancement and stabilization of traffic flow by moving in groups.
AB  - We study the traffic behavior of vehicles moving in groups analytically and
      numerically. A car-following model of traffic is extended to take into account a
      binary mixture of vehicles. It is shown that the movement in groups stabilizes
      the traffic flow. The jamming transition among the free traffic, the
      inhomogeneous traffic, and the homogeneous congested traffic occurs at a higher
      density than the threshold of the original model. The traffic current is highly
      enhanced at a high-density region by keeping a short headway without jam. The
      jamming transition is analyzed by using the linear stability method. It is found
      that the theoretical neutral stability curve agrees with the transition line
      obtained by the simulation.

PMID- 11461331
TI  - Phases of a conserved mass model of aggregation with fragmentation at fixed
      sites.
AB  - To study the effect of quenched disorder in a class of reaction-diffusion
      systems, we introduce a conserved mass model of diffusion and aggregation in
      which fragmentation occurs only at certain fixed sites. On most sites, the mass
      moves as a whole to a nearest neighbor while it leaves the fixed sites only as a
      single monomer (i.e., chips off). Once the mass leaves any site, it coalesces
      with the mass present on its neighbor. We study in detail the effect of a single
      chipping site on the steady state in arbitrary dimensions, with and without bias.
      In the thermodynamic limit, the system can exist in one of the following three
      phases. (a) Pinned aggregate (PA) phase in which an infinite aggregate (with mass
      proportional to the volume of the system) appears at the chipping site with
      probability one but not in the bulk. (b) Unpinned aggregate (UA) phase in which
      the infinite aggregate occurs at the chipping site with a probability strictly
      less than one and can coexist with infinite aggregates in the bulk. (c)
      Nonaggregate (NA) phase in which there is no infinite cluster. The steady state
      of the system depends on the dimension and drive. A sitewise inhomogeneous mean
      field theory predicts that the system exists in the UA phase in all cases. Monte
      Carlo simulations in one and two dimensions support this prediction in all but
      one-dimensional, biased case. In the latter case, there is a phase transition
      from the NA phase to the PA phase as the density is increased. We identify the
      critical point exactly and calculate the mass distribution in the PA phase. The
      NA phase and the critical point are studied by Monte Carlo simulations and using
      scaling arguments. A variant of the above aggregation model is also considered in
      which total particle number is conserved and chipping occurs at a fixed site, but
      the particles do not interact with each other at other sites. This model is
      solved exactly by mapping it to a zero range process. With increasing density, it
      exhibits a phase transition from the NA phase to the PA phase in all dimensions,
      irrespective of bias. The free-particle model is also solved with an extensive
      number of chipping sites with random chipping rates and we argue that it
      qualitatively describes the behavior of the aggregation model with extensive
      disorder.

PMID- 11461332
TI  - Field theory of self-organized fractal etching.
AB  - We propose a phenomenological field theoretical approach to the chemical etching
      of a disordered solid. The theory is based on a recently proposed dynamical
      etching model. Through the introduction of a set of Langevin equations for the
      model evolution, we are able to map the problem into a field theory related to
      isotropic percolation. To the best of the author's knowledge, this constitutes
      the first application of field theory to a problem of chemical dynamics. By using
      this mapping, many of the etching process critical properties are seen to be
      describable in terms of the percolation renormalization group fixed point. The
      emerging field theory has the peculiarity of being self-organized in the sense
      that without any parameter fine tuning the system develops fractal properties up
      to a certain scale controlled solely by the volume V of the etching solution. In
      the limit V-->infinity the upper cutoff goes to infinity and the system becomes
      scale invariant. We present also a finite size scaling analysis and discuss the
      relation of this particular etching mechanism to gradient percolation. Finally,
      the possibility of considering this mechanism as a generic path to self-organized
      criticality is analyzed, with the characteristics of being closely related to a
      real physical system and therefore more directly accessible to experiments.

PMID- 11461333
TI  - Disorder and plasticity in the fragmentation of coatings.
AB  - Using a one-dimensional model that takes into account ideal plasticity of the
      surface layer, we investigate the fragmentation of thin coatings under uniaxial
      tension. The coating is modeled as a chain of plastically deforming elements that
      are connected via leaf springs to a uniformly stretched substrate. Each coating
      element can only withstand a maximum elongation, which is randomly distributed.
      From simulations of the fragmentation process we find that the average crack
      spacing <L> scales with applied strain epsilon, i.e., <L> proportional to
      epsilon(-kappa). Simulations and analytical arguments show that the scaling
      exponent kappa depends on the disorder parameters of the model.

PMID- 11461334
TI  - Defect statistics in the two-dimensional complex Ginzburg-Landau model.
AB  - The statistical correlations between defects in the two-dimensional complex
      Ginzburg-Landau model are studied in the defect-coarsening regime. In particular
      the defect-velocity probability distribution is determined and has the same high
      velocity tail found for the purely dissipative time-dependent Ginzburg-Landau
      (TDGL) model. The spiral arms of the defects lead to a very different behavior
      for the order parameter correlation function in the scaling regime compared to
      the results for the TDGL model.

PMID- 11461335
TI  - Model of C60 fullerene, (H2O)60 water, and other similar clusters.
AB  - An analytical calculation of the partition function for the lattice gas model of
      a finite fullerene type cluster and of an infinite nanotube type cluster is
      presented. The method of calculation is based on the Vdovichenko random walk
      approach. There appear to be two values of critical temperature, and the heat
      capacity in their vicinities is proportional to (T-T(c))(-1).

PMID- 11461336
TI  - Noise robust estimates of correlation dimension and K2 entropy.
AB  - Using Gaussian kernels to define the correlation sum we derive simple formulas
      that correct the noise bias in estimates of the correlation dimension and K2
      entropy of chaotic time series. The corrections are only based on the difference
      of correlation dimensions for adjacent embedding dimensions and hence preserve
      the full functional dependencies on both the scale parameter and embedding
      dimension. It is shown theoretically that the estimates, which are derived for
      additive white Gaussian noise, are also robust for moderately colored noise.
      Simulations underline the usefulness of the proposed correction schemes. It is
      demonstrated that the method gives satisfactory results also for non-Gaussian and
      dynamical noise.

PMID- 11461337
TI  - Spirals and targets in reaction-diffusion systems.
AB  - The existence of spirals and targets is common in reaction diffusion systems of
      excitable dynamics. I present a multiple scale perturbation analysis to show the
      existence of all these patterns near a Hopf bifurcation boundary in a Turing type
      reaction-diffusion system.

PMID- 11461338
TI  - Solution of the modified Helmholtz equation in a triangular domain and an
      application to diffusion-limited coalescence.
AB  - A new transform method for solving boundary value problems for linear and
      integrable nonlinear partial differential equations recently introduced in the
      literature is used here to obtain the solution of the modified Helmholtz equation
      q(xx)(x,y)+q(yy)(x,y)-4 beta(2)q(x,y)=0 in the triangular domain 0< or =x< or =L
      y< or =L, with mixed boundary conditions. This solution is applied to the problem
      of diffusion-limited coalescence, A+A<==>A, in the segment (-L/2,L/2), with traps
      at the edges.

PMID- 11461339
TI  - Global hydration kinetics of tricalcium silicate cement.
AB  - We reconsider a number of measurements for the overall hydration kinetics of
      tricalcium silicate pastes having an initial water to cement weight ratio close
      to 0.5. We find that the time dependent ratio of hydrated and unhydrated silica
      mole numbers can be well characterized by two power laws in time, x/(1-x)
      approximately (t/t(x))(psi). For early times t<t(x) we find an "accelerated"
      hydration (psi=5/2) and for later times t>t(x) a parabolic behavior (psi=1/2).
      The crossover time is estimated as t(x) approximately 16 h. We interpret these
      results in terms of a global second-order rate equation indicating that (a)
      hydrates catalyze the hydration process for t<t(x), (b) they inhibit further
      hydration for t>t(x), and (c) the value of the associated rate constant is of
      magnitude 6 x 10(-7) - 7 x 10(-6) l mol(-1) s(-1). We argue, by considering that
      the hydration process actually occurs via diffusion limited precipitation, that
      the exponents psi=5/2 and psi=1/2 directly indicate a preferentially plate-like
      hydrate microstructure. This is essentially in agreement with experimental
      observations of cellular hydrate microstructures for this class of materials.

PMID- 11461340
TI  - Characterization of structural reorganization in rice piles.
AB  - Diagnostics applied to a rice-pile cellular automaton reveal different mechanisms
      producing power-law behaviors of statistical attributes of grains which are
      germane to self organised critical phenomena. The probability distributions for
      these quantities can be derived from two distinct random walk models that account
      for correlated clustered behavior through incorporating fluctuations in the
      number of steps in the walk. The first model describes the distribution for a
      spatial quantity, the resultant flight length of grains. This has a power-law
      tail caused by grains moving through a discrete, power-law distributed number of
      random steps of finite length. Developing this model into a random walk obtains
      distributions for the resultant flight length with characteristics similar to
      Levy distributions. The second random walk model is devised to explain a temporal
      quantity, the distribution of "trapping" or "residence" times of grains at single
      locations in the pile. Diagnostics reveal that the trapping time can be
      constructed as a sum of "subtrapping times," which are described by a Levy
      distribution where the number of terms in the sum is a discrete random variable
      accurately described by a negative binomial distribution. The infinitely
      divisible, two-parameter, limit distribution for the resultant of such a random
      walk is discussed, and describes a dual-scale power-law behavior if the number
      fluctuations are strongly clustered. The form for the distribution of transit
      times of grains results as a corollary.

PMID- 11461341
TI  - Convergence to equilibrium in a class of interacting particle systems evolving in
      discrete time.
AB  - We conjecture that for a wide class of interacting particle systems evolving in
      discrete time, namely, conservative cellular automata with piecewise linear flow
      diagrams, relaxation to the limit set follows the same power law at critical
      points. We further describe the structure of the limit sets of such systems as
      unions of shifts of finite type. Relaxation to the equilibrium resembles
      ballistic annihilation, with "defects" propagating in opposite directions
      annihilating upon collision.

PMID- 11461342
TI  - Scaling theory for two-dimensional systems with competing interactions.
AB  - We derive an analytic scaling theory for a two-dimensional system in which
      spontaneous patterns of stripes, bubbles, and intermediately shaped domains arise
      due to the competition of short-range attractions and long-range dipolar
      repulsions. The theory predicts temperature and domain-size scaling as a function
      of the relative repulsion strength eta, the ratio of the repulsive to the
      attractive coupling constant in the system's Hamiltonian. As eta decreases, the
      domain size explodes exponentially and the melting temperature for a system of
      ordered stripes increases. Our findings shed new light on the phase diagram and
      critical excitations for the dipolar Ising ferromagnet or lattice gas and their
      continuum analogs. We show that the features described by the scaling theory are
      insensitive to details like cutoffs for the dipolar interactions and, therefore,
      should be widely applicable. Our corresponding states analysis explains the
      experimentally observed stripe melting upon compression in a Langmuir monolayer.
      A phenomenological extension of the analytic scaling theory describes how the
      system's behavior is modified in the presence of magnetization or density
      fluctuations. Fluctuations are found to suppress domain size and the stripe
      melting temperature. In regimes where fluctuations are important, we predict that
      domain size will decrease with increasing temperature.

PMID- 11461343
TI  - Transition from random to ordered fractals in fragmentation of particles in an
      open system.
AB  - We consider the fragmentation process with mass loss and discuss self-similar
      properties of the arising structure both in time and space, focusing on
      dimensional analysis. This exhibits a spectrum of mass exponents theta, whose
      exact numerical values are given for which x(-theta) or t(theta z) has the
      dimension of particle size distribution function psi(x,t), where z is the kinetic
      exponent. We obtained conditions for which the scaling and fragmentation process
      altogether breaks down, and we give an explicit scaling solution for a special
      case. Finally, we identify a new class of fractals ranging from random to
      nonrandom and show that the fractal dimension increases with increasing order and
      a transition to a strictly self-similar pattern occurs when randomness completely
      ceases.

PMID- 11461344
TI  - First-passage-time exponent for higher-order random walks: using Levy flights.
AB  - We present a heuristic derivation of the first-passage-time exponent for the
      integral of a random walk [Y. G. Sinai, Theor. Math. Phys. 90, 219 (1992)].
      Building on this derivation, we construct an estimation scheme to understand the
      first-passage-time exponent for the integral of the integral of a random walk,
      which is numerically observed to be 0.220+/-0.001. We discuss the implications of
      this estimation scheme for the nth integral of a random walk. For completeness,
      we also address the n=infinity case. Finally, we explore an application of these
      processes to an extended, elastic object being pulled through a random potential
      by a uniform applied force. In so doing, we demonstrate a time reparametrization
      freedom in the Langevin equation that maps nonlinear stochastic processes into
      linear ones.

PMID- 11461345
TI  - Quantum field theory of treasury bonds.
AB  - The Heath-Jarrow-Morton (HJM) formulation of treasury bonds in terms of forward
      rates is recast as a problem in path integration. The HJM model is generalized to
      the case where all the forward rates are allowed to fluctuate independently. The
      resulting theory is shown to be a two-dimensional Gaussian quantum field theory.
      The no arbitrage condition is obtained and a functional integral derivation is
      given for the price of a futures and an options contract.

PMID- 11461346
TI  - Central role of the observable electric potential in transport equations.
AB  - Nonequilibrium systems are usually studied in the framework of transport
      equations that involve the true electric potential (TEP), a nonobservable
      variable. Nevertheless another electric potential, the observable electric
      potential (OEP), may be defined to construct a useful set of transport equations.
      In this paper several basic characteristics of the OEP are deduced and
      emphasized: (i) the OEP distribution depends on thermodynamic state of the
      solution, (ii) the observable equations have a reference value for all other
      transport equations, (iii) the bridge that connects the OEP with a certain TEP is
      usually defined by the ion activity coefficient, (iv) the electric charge density
      is a nonobservable variable, and (v) the OEP formulation constitutes a natural
      model for studying the fluxes in membrane systems.

PMID- 11461347
TI  - Scaling behavior of the absorbing phase transition in a conserved lattice gas
      around the upper critical dimension.
AB  - We analyze numerically the critical behavior of a conserved lattice gas that was
      recently introduced as an example of the new universality class of absorbing
      phase transitions with a conserved field [Phys. Rev. Lett. 85, 1803 (2000)]. We
      determine the critical exponent of the order parameter as well as the critical
      exponent of the order parameter fluctuations in D=2,3,4,5 dimensions. A
      comparison of our results and those obtained from a mean-field approach and a
      field theory suggests that the upper critical dimension of the absorbing phase
      transition is four.

PMID- 11461348
TI  - First- and second-order phase transitions in a driven lattice gas with nearest
      neighbor exclusion.
AB  - A lattice gas with infinite repulsion between particles separated by < or = 1
      lattice spacing, and nearest-neighbor hopping dynamics, is subject to a drive
      favoring movement along one axis of the square lattice. The equilibrium (zero
      drive) transition to a phase with sublattice ordering, known to be continuous,
      shifts to lower density, and becomes discontinuous for large bias. In the ordered
      nonequilibrium steady state, both the particle and order-parameter densities are
      nonuniform, with a large fraction of the particles occupying a jammed strip
      oriented along the drive. The drive thus induces separation into high- and low
      density regions in a system with purely repulsive interactions. Increasing the
      drive can provoke a transition to the ordered phase, and thereby, a sharp
      reduction in current.

PMID- 11461349
TI  - Equilibrium crystal shapes in the Potts model.
AB  - The three-dimensional q-state Potts model, forced into coexistence by fixing the
      density of one state, is studied for q=2, 3, 4, and 6. As a function of
      temperature and number of states, we studied the resulting equilibrium droplet
      shapes. A theoretical discussion is given of the interface properties at large
      values of q. We found a roughening transition for each of the numbers of states
      we studied, at temperatures that decrease with increasing q, but increase when
      measured as a fraction of the melting temperature. We also found equilibrium
      shapes closely approaching a sphere near the melting point, even though the three
      dimensional Potts model with three or more states does not have a phase
      transition with a diverging length scale at the melting point.

PMID- 11461350
TI  - Systematic approximation method for the critical properties of lattice spin
      systems.
AB  - We present an extension of past approximations such as the Bethe approximation
      where we look at generalized Husimi trees. In doing so we obtain a sequence of
      ever more accurate approximations. The sequence is very systematic, and sequences
      of as few as three points can be extrapolated to give critical temperature
      estimates to within 0.1% or better of the exact value for our test cases. In the
      case of the square lattice, Ising ferromagnet, where five levels of approximation
      are obtained, estimates within 0.003% are obtained. Critical exponents can also
      be approximated but with much less accuracy. Much of our attention is devoted to
      the critical line of the phase diagram of the antiferromagnetic Ising model on
      the square lattice, where our results compare very favorably with other
      approximations. The method is general enough to be applicable to any spin lattice
      system where the spin takes on a discrete set of values.

PMID- 11461351
TI  - Universal scaling functions for bond percolation on planar-random and square
      lattices with multiple percolating clusters.
AB  - Percolation models with multiple percolating clusters have attracted much
      attention in recent years. Here we use Monte Carlo simulations to study bond
      percolation on L1xL2 planar random lattices, duals of random lattices, and square
      lattices with free and periodic boundary conditions, in vertical and horizontal
      directions, respectively, and with various aspect ratios L(1)/L(2). We calculate
      the probability for the appearance of n percolating clusters, W(n); the
      percolating probabilities P; the average fraction of lattice bonds (sites) in the
      percolating clusters, <c(b)>(n) (<c(s)>(n)), and the probability distribution
      function for the fraction c of lattice bonds (sites), in percolating clusters of
      subgraphs with n percolating clusters, f(n)(c(b)) [f(n)(c(s))]. Using a small
      number of nonuniversal metric factors, we find that W(n), P, <c(b)>(n)
      (<c(s)>(n)), and f(n)(c(b)) [f(n)(c(s))] for random lattices, duals of random
      lattices, and square lattices have the same universal finite-size scaling
      functions. We also find that nonuniversal metric factors are independent of
      boundary conditions and aspect ratios.

PMID- 11461352
TI  - Isothermal-isobaric ensemble for small systems.
AB  - The application of the isothermal-isobaric (N-P-T) ensemble to small systems is
      considered. In the small system limit, which is currently gaining in scientific
      and technological significance, a volume scale must be introduced in order to
      obtain a partition function that is dimensionless. The volume scale, however,
      must be carefully chosen since it depends upon the nature of the boundary
      separating the system from the surroundings. If the incorrect volume scale is
      used, the resulting N-P-T ensemble partition function will not rigorously
      describe the small system of interest. Although volume scales become
      inconsequential in the thermodynamic limit, care must be exercised in formulating
      the ensembles used to study small systems.

PMID- 11461353
TI  - Front dynamics in the presence of spatiotemporal structured noises.
AB  - Front dynamics modeled by a reaction-diffusion equation are studied under the
      influence of spatiotemporal structured noises. An effective deterministic model
      is analytical derived where the noise parameters, intensity, correlation time,
      and correlation length appear explicitly. The different effects of these
      parameters are discussed for the Ginzburg-Landau and Schlogl models. We obtain an
      analytical expression for the front velocity as a function of the noise
      parameters. Numerical simulation results are in a good agreement with the
      theoretical predictions.

PMID- 11461354
TI  - Dynamical quenching and annealing in self-organization multiagent models.
AB  - We study the dynamics of a generalized minority game (GMG) and of the bar
      attendance model (BAM) in which a number of agents self-organize to match an
      attendance that is fixed externally as a control parameter. We compare the usual
      dynamics used for the minority game with one for the BAM that makes a better use
      of the available information. We study the asymptotic states reached in both
      frameworks. We show that states that can be assimilated to either thermodynamic
      equilibrium or quenched configurations can appear in both models, but with
      different settings. We discuss the relevance of the parameter G that measures the
      value of the prize for winning in units of the fine for losing. We also provide
      an annealing protocol by which the quenched configurations of the GMG can
      progressively be modified to reach an asymptotic equilibrium state that coincides
      with the one obtained with the BAM.

PMID- 11461355
TI  - Scientific collaboration networks. I. Network construction and fundamental
      results.
AB  - Using computer databases of scientific papers in physics, biomedical research,
      and computer science, we have constructed networks of collaboration between
      scientists in each of these disciplines. In these networks two scientists are
      considered connected if they have coauthored one or more papers together. We
      study a variety of statistical properties of our networks, including numbers of
      papers written by authors, numbers of authors per paper, numbers of collaborators
      that scientists have, existence and size of a giant component of connected
      scientists, and degree of clustering in the networks. We also highlight some
      apparent differences in collaboration patterns between the subjects studied. In
      the following paper, we study a number of measures of centrality and
      connectedness in the same networks.

PMID- 11461356
TI  - Scientific collaboration networks. II. Shortest paths, weighted networks, and
      centrality.
AB  - Using computer databases of scientific papers in physics, biomedical research,
      and computer science, we have constructed networks of collaboration between
      scientists in each of these disciplines. In these networks two scientists are
      considered connected if they have coauthored one or more papers together. Here we
      study a variety of nonlocal statistics for these networks, such as typical
      distances between scientists through the network, and measures of centrality such
      as closeness and betweenness. We further argue that simple networks such as these
      cannot capture variation in the strength of collaborative ties and propose a
      measure of collaboration strength based on the number of papers coauthored by
      pairs of scientists, and the number of other scientists with whom they coauthored
      those papers.

PMID- 11461357
TI  - Lyapunov exponents and transport in the Zhang model of self-organized
      criticality.
AB  - We discuss the role played by Lyapunov exponents in the dynamics of Zhang's model
      of self-organized criticality. We show that a large part of the spectrum (the
      slowest modes) is associated with energy transport in the lattice. In particular,
      we give bounds on the first negative Lyapunov exponent in terms of the energy
      flux dissipated at the boundaries per unit of time. We then establish an explicit
      formula for the transport modes that appear as diffusion modes in a landscape
      where the metric is given by the density of active sites. We use a finite size
      scaling ansatz for the Lyapunov spectrum, and relate the scaling exponent to the
      scaling of quantities such as avalanche size, duration, density of active sites,
      etc.

PMID- 11461358
TI  - Kinetic Ashkin-Teller model with competing dynamics.
AB  - We study a two-dimensional nonequilibrium Ashkin-Teller model based on competing
      dynamics induced by contact with a heat bath at temperature T, and subject to an
      external source of energy. The dynamics of the system is simulated by two
      competing stochastic processes: a Glauber dynamics with probability p, which
      simulates the contact with the heat bath; and a Kawasaki dynamics with
      probability 1-p, which takes into account the flux of energy into the system.
      Monte Carlo simulations were employed to determine the phase diagram for the
      stationary states of the model and the corresponding critical exponents. The
      phase diagrams of the model exhibit a self-organization phenomenon for certain
      values of the fourth coupling interaction strength. On the other hand, from
      exponent calculations, the equilibrium critical behavior is preserved when
      nonequilibrium conditions are applied.

PMID- 11461359
TI  - Nonlinear random resistor diode networks and fractal dimensions of directed
      percolation clusters.
AB  - We study nonlinear random resistor diode networks at the transition from the
      nonpercolating to the directed percolating phase. The resistor-like bonds and the
      diode-like bonds under forward bias voltage obey a generalized Ohm's law V
      approximately I(r). Based on general grounds such as symmetries and relevance we
      develop a field theoretic model. We focus on the average two-port resistance,
      which is governed at the transition by the resistance exponent straight phi(r).
      By employing renormalization group methods we calculate straight phi(r) for
      arbitrary r to one-loop order. Then we address the fractal dimensions
      characterizing directed percolation clusters. Via considering distinct values of
      the nonlinearity r, we determine the dimension of the red bonds, the chemical
      path, and the backbone to two-loop order.

PMID- 11461360
TI  - Detection of hidden regimes in stochastic cyclostationary time series.
AB  - Stationary stochastic time series with nonlinear dynamics can feature a
      probability density function (PDF) with distinct local maxima associated with
      distinct regimes. For nonstationary time series, on the other hand, such regimes
      are not necessarily reflected in the shape of the PDF. This occurs when the
      duration of a regime is too short for the PDF to adjust, and such a regime is
      called a "hidden" regime. This paper presents an algorithm that allows one to
      detect hidden regimes in cyclostationary stochastic Markovian time series. The
      method involves analysis of an appropriately windowed time series, from which the
      drift and diffusion coefficients of the associated Fokker-Planck equation are
      estimated. The success of the algorithm is illustrated using synthetic time
      series with both additive and multiplicative noise.

PMID- 11461361
TI  - Controlling dissipative and Hamiltonian chaos by a constant periodic pulse
      method.
AB  - A constant periodic pulse method is proposed to control dissipative and
      Hamiltonian chaos. Using the convergence of the chaotic orbit in finite time, the
      stable segment of the chaotic orbit that satisfies the desired dynamical features
      can be made to form a closed orbit by the action of a proper perturbation on the
      system variables. A way to determine the intensity of the perturbation and the
      corresponding fixed points is presented. The method is robust against the
      presence of external noise.

PMID- 11461362
TI  - Dynamical instability of the motion of atoms in a silicon crystal.
AB  - The dynamical nature of the motion of atoms in a silicon crystal is investigated
      from the information theoretic standpoint with time series analysis about
      numerical solutions of molecular dynamics simulation. The atomic motion exhibits
      exponential decay of information entropy with a characteristic time scale of
      approximately 40 x 10(-15) sec. This observation may be interpreted as a
      signature of microscopic dynamical instability in solids.

PMID- 11461363
TI  - Application of the Nose-Hoover method to optimization problems.
AB  - A solution for continuous optimization problems is proposed using the Nose-Hoover
      method. The proposed method aims for compatibleness, which has been a problem in
      many past solutions, between two requirements: searching with a high probability
      for finding candidates for the optimal points, and searching quickly in a
      feasible region. The Nose-Hoover equation is used, where coordinates of a
      physical system are treated as the decision variables in a given optimization
      problem and a potential function is replaced by -k(B)T times the logarithm of an
      arbitrary density function for coordinate variables. The density can be set such
      that the visiting weight of the orbits to the equation has high values at areas
      where the objective function of the problem has low (high) values. Furthermore, a
      high value for the speed of the orbits can be set independently. Under an
      assumption of ergodicity, these values for the visiting weight and speed of the
      orbits are realized by long-time limits. Consequently, the two requirements can
      be satisfied. In numerical simulations assuming an objective function, the finite
      time validity of the properties formulated with the long-time limits and the
      applicability of the proposed method to actual optimization problems were
      confirmed.

PMID- 11461364
TI  - Scarring effects on tunneling in chaotic double-well potentials.
AB  - The connection between scarring and tunneling in chaotic double-well potentials
      is studied in detail through the distribution of level splittings. The mean level
      splitting is found to have oscillations as a function of energy, as expected if
      scarring plays a role in determining the size of the splittings, and the spacing
      between peaks is observed to be periodic of period 2 pi Planck's over 2 pi in
      action. Moreover, the size of the oscillations is directly correlated with the
      strength of scarring. These results are interpreted within the theoretical
      framework of Creagh and Whelan. The semiclassical limit and finite-Planck's over
      2 pi effects are discussed, and connections are made with reaction rates and
      resonance widths in metastable wells.

PMID- 11461365
TI  - Nonperiodic delay mechanism and fractallike behavior in classical time-dependent
      scattering.
AB  - We study the occurrence of delay mechanisms other than periodic orbits in
      scattering systems with time-dependent potentials. By using as model system two
      harmonically oscillating disks on a plane, we have found the existence of a
      mechanism not related to the periodic orbits of the system, that delays
      trajectories in the scattering region. This mechanism creates a fractallike
      structure in the scattering functions and can possibly occur in several time
      dependent scattering systems.

PMID- 11461366
TI  - Ansatz library for global modeling with a structure selection.
AB  - The information contained in a scalar time series and its time derivatives is
      used to obtain a global model for the underlying dynamics. This model provides a
      description of the time evolution of the system studied in a space spanned by the
      time series and its successive time derivatives which is expected to be
      equivalent to the original phase space. Differential models are, in general, very
      complicated and do not necessarily capture all properties of the original
      dynamics. The possibility of choosing a form among an ansatz library for the
      original system which allows a structure selection for the differential model is
      considered. It allows for the reduction of the complexity of the model and the
      recovery of the right property when the differential model is transformed back
      into the space associated with the ansatz.

PMID- 11461367
TI  - Stochastic analog to phase transitions in chaotic coupled map lattices.
AB  - Stochastic dynamical systems are shown to exhibit the same order-disorder phase
      transitions that have been found in chaotic map lattices. Phase diagrams are
      obtained for diffusively coupled two-dimensional (2D) lattices, using two
      stochastic maps and a chaotic one, for both square and triangular geometries,
      with simultaneous updating. We show how the use of triangular geometry reduces
      (or even eliminates) the reentrant behavior found in the phase diagrams for the
      square geometry. This is attributed to the elimination (via frustration) of the
      antiferromagnetic clusters common to simultaneous updating of square lattices. We
      also evaluate the critical exponents for the stochastic maps in the triangular
      lattices. The strong similarities in the phase diagrams and the consistency
      between the critical exponents of one stochastic map and the chaotic one,
      evaluated in an early work by Marcq et al. [Phys. Rev. Lett. 77, 4003 (1996);
      Phys. Rev. E 55, 2606 (1997)] suggest that the "sign-persistence," defined as the
      probability that the local map keeps the sign of the local variable in one
      iteration, plays a fundamental role in the presence of continuous phase
      transitions in coupled map lattices, and is a basic ingredient for models that
      belong to this weak Ising universality. However, the fact that the second
      stochastic map, which has an extremely simple local dynamics, seems to fall in
      the 2D Ising universality class, suggests that some minimal local complexity is
      also needed to generate the specific correlations that end up giving non-Ising
      critical behavior.

PMID- 11461368
TI  - Pinch resonances in a radio-frequency-driven superconducting-quantum-interference
      device ring-resonator system.
AB  - In this paper we present experimental data on the frequency domain response of a
      superconducting-quantum-interference-device ring (a Josephson weak link enclosed
      by a thick superconducting ring) coupled to a radio frequency tank circuit
      resonator. We show that with the ring weakly hysteretic the resonance line shape
      of this coupled system can display opposed fold bifurcations that appear to touch
      (pinch off). We demonstrate that for appropriate circuit parameters these pinch
      off line shapes exist as solutions of the nonlinear equations of motion for the
      system.

PMID- 11461369
TI  - Effective normalization of complexity measurements for epoch length and sampling
      frequency.
AB  - The algorithmic complexity of a symbol sequence is sensitive to the length of the
      message. Additionally, in those cases where the sequence is constructed by the
      symbolic reduction of an experimentally observed wave form, the corresponding
      value of algorithmic complexity is also sensitive to the sampling frequency. In
      this contribution, we present definitions of algorithmic redundancy that are
      sequence-sensitive generalizations of Shannon's original definition of
      information redundancy. In contrast with algorithmic complexity, we demonstrate
      that algorithmic redundancy is not sensitive to message length or to observation
      scale (sampling frequency) when stationary systems are examined.

PMID- 11461370
TI  - Functional dependence and quasiperiodicity in the spatiotemporal dynamics of
      yttrium iron garnet films.
AB  - When thin films of yttrium iron garnet (YIG) are placed in a magnetic field and
      driven at microwave (rf) frequencies, nonlinear interactions within the material
      cause the normal microwave spin precession to be modulated at lower frequencies.
      We measure these lower frequency (kHz) signals at two spatially separated
      locations on the YIG film and use linear and nonlinear analysis to study the
      functional dependence of the spin dynamics at one location on the spin dynamics
      at the other location. We see dynamical states where nonlinear analysis can
      detect a functional dependence that the linear analysis fails to reveal.

PMID- 11461371
TI  - Effect of asymmetry on the loss of chaos synchronization.
AB  - We investigate the effect of asymmetry of coupling on the bifurcation mechanism
      for the loss of synchronous chaos in coupled systems. It is found that only when
      the symmetry-breaking pitchfork bifurcations take part in the process of the
      synchronization loss for the case of symmetric coupling, the asymmetry changes
      the bifurcation scenarios of the desynchronization. For the case of weak
      coupling, pitchfork bifurcations of asynchronous periodic saddles are replaced by
      saddle-node bifurcations, while for the case of strong coupling, pitchfork
      bifurcations of synchronous periodic saddles transform to transcritical
      bifurcations. The effects of the saddle-node and transcritical bifurcations for
      the weak asymmetry are similar to those of the pitchfork bifurcations for the
      symmetric-coupling case. However, with increasing the "degree" of the asymmetry,
      their effects change qualitatively, and eventually become similar to those for
      the extreme case of unidirectional asymmetric coupling.

PMID- 11461372
TI  - Intermittent phase synchronization of coupled spatiotemporal chaotic systems.
AB  - Phase synchronization is studied with a discrete system formed by two coupled map
      lattices, in which phases are measured in two-dimensional vectors. Simulation
      results show that by imposing external coupling between the two lattices, phase
      synchronization can be found in all two-dimensional phase planes between them.
      When the system is approaching the phase synchronizing state, unstable phase
      synchronization is observed. This is referred to as intermittent phase
      synchronization that appears when the trajectories on two interacting phase
      planes have opposite directions of rotation but with only a small phase
      difference. The intermittent phase synchronization could also be observed in
      coupled autonomous systems with diffusive attractors although their phase
      concepts are inconsistent. Our results show that the intermittent phase
      synchronization of both discrete and autonomous systems relates to the diffusion
      or the complexity of the attractors.

PMID- 11461373
TI  - Bootstrap estimates of chaotic dynamics.
AB  - Bootstrap sampling is a nonparametric method for estimating the standard error of
      a statistic. This paper describes the application of bootstrap sampling to
      estimate the error in local linear approximations of the dynamics on chaotic
      attractors reconstructed from time series measurements. We present an algorithm
      for identifying influential points, i.e., observations with an especially large
      effect on a least-squares fit, and an algorithm to estimate the standard error of
      regression coefficients obtained from total least squares. We also consider the
      application of bootstrap methods to assess the uncertainty in Lyapunov exponent
      computations from chaotic time series.

PMID- 11461374
TI  - Chaotic behavior in lemon-shaped billiards with elliptical and hyperbolic
      boundary arcs.
AB  - Chaotic properties of a new family, ellipse hyperbola billiards (EHB), of lemon
      shaped two-dimensional billiards, interpolating between the square and the
      circle, whose boundaries consist of hyperbolic, parabolic, or elliptical
      segments, depending on the shape parameter delta, are investigated classically
      and quantally. Classical chaotic fraction is calculated and compared with the
      quantal level density fluctuation measures obtained by fitting the calculated
      level spacing sequences with the Brody, Berry-Robnik, and Berry-Robnik-Brody
      distributions. Stability of selected classical orbits is investigated, and for
      some special hyperbolic points in the Poincare sections, the "blinking island"
      phenomenon is observed. Results for the EHB billiards are compared with the
      properties of the family of generalized power-law lemon-shaped billiards.

PMID- 11461375
TI  - Front propagation of spatiotemporal chaos.
AB  - We study the dynamics of the front separating a spatiotemporally chaotic region
      from a stable steady region using a simple model applicable to periodically
      forced systems. In particular, we investigate both the coarsening of the front
      induced by the inherent "noise" of the chaotic region, and the long wavelength
      dynamics causing the front to develop cusps.

PMID- 11461376
TI  - Estimation of large-scale dimension densities.
AB  - We propose a technique to calculate large-scale dimension densities in both
      higher-dimensional spatio-temporal systems and low-dimensional systems from only
      a few data points, where known methods usually have an unsatisfactory scaling
      behavior. This is mainly due to boundary and finite-size effects. With our rather
      simple method, we normalize boundary effects and get a significant correction of
      the dimension estimate. This straightforward approach is based on rather general
      assumptions. So even weak coherent structures obtained from small spatial
      couplings can be detected with this method, which is impossible by using the
      Lyapunov-dimension density. We demonstrate the efficiency of our technique for
      coupled logistic maps, coupled tent maps, the Lorenz attractor, and the Roessler
      attractor.

PMID- 11461377
TI  - Multivalued mappings in generalized chaos synchronization.
AB  - The onset of generalized synchronization of chaos in directionally coupled
      systems corresponds to the formation of a continuous mapping that enables one to
      persistently define the state of the response system from the trajectory of the
      drive system. A recently developed theory of generalized synchronization of chaos
      deals only with the case where this synchronization mapping is a single-valued
      function. In this paper, we explore generalized synchronization in a regime where
      the synchronization mapping can become a multivalued function. Specifically, we
      study the properties of the multivalued mapping that occurs between the drive and
      response systems when the systems are synchronized with a frequency ratio other
      than one-to-one, and address the issues of the existence and continuity of such
      mappings. The basic theoretical framework underlying the considered
      synchronization regimes is then developed.

PMID- 11461378
TI  - Bifurcations and global stability of synchronized stationary states in the
      Kuramoto model for oscillator populations.
AB  - Bistability between synchronized stationary states is shown to occur in large
      populations of nonlinearly coupled random oscillators (Kuramoto model), governed
      by trimodal natural frequency distributions. Numerical simulations and a
      numerical investigation of bifurcating states provide evidence of global
      stability of such states, subject to unimodal, bimodal, and trimodal frequency
      distributions. All this may be important in the framework of large
      superconducting Josephson junctions arrays, as well as of neural networks.

PMID- 11461379
TI  - Structure of wave functions in (1+2)-body random matrix ensembles.
AB  - Random matrix ensembles defined by a mean-field one body plus a chaos generating
      random two-body interaction [called embedded ensembles of (1+2)-body
      interactions] predict for wave functions, in the chaotic domain, an essentially
      one-parameter Gaussian forms for the energy dependence of the number of principal
      components (NPC) and the localization length l(H) (defined by information
      entropy), which are two important measures of chaos in finite interacting many
      particle systems. Numerical embedded ensemble calculations and nuclear shell
      model results, for NPC and l(H), are compared with the theory. These analyses
      clearly point out that for realistic finite interacting many-particle systems, in
      the chaotic domain, wave-function structure is given by (1+2)-body embedded
      random matrix ensembles.

PMID- 11461380
TI  - Perturbed on-off intermittency.
AB  - A basic requirement for on-off intermittency to occur is that the system
      possesses an invariant subspace. We address how on-off intermittency manifests
      itself when a perturbation destroys the invariant subspace. In particular, we
      distinguish between situations where the threshold for measuring the on-off
      intermittency in numerical or physical experiments is much larger than or is
      comparable to the size of the perturbation. Our principal result is that, as the
      perturbation parameter increases from zero, a metamorphosis in on-off
      intermittency occurs in the sense that scaling laws associated with physically
      measurable quantities change abruptly. A geometric analysis, a random-walk model,
      and numerical computations support the result.

PMID- 11461381
TI  - Chaos-assisted tunneling with cold atoms.
AB  - In the context of quantum chaos, both theory and numerical analysis predict large
      fluctuations of the tunneling transition probabilities when irregular dynamics is
      present at the classical level. Here we consider the nondissipative quantum
      evolution of cold atoms trapped in a time-dependent modulated periodic potential
      generated by two laser beams. We give some precise guidelines for the observation
      of chaos-assisted tunneling between invariant phase space structures paired by
      time-reversal symmetry.

PMID- 11461382
TI  - Identifying physical properties of a CO2 laser by dynamical modeling of measured
      time series.
AB  - We estimate internal parameters of a Q-switched CO2 laser by fitting trajectories
      of the four-level model to measured scalar time series. The four-level model is a
      five-dimensional nonlinear system of ordinary differential equations. A multiple
      shooting technique is used to construct the unobserved time courses of the
      population densities and to reveal the dependence of the parameters on the
      excitation current. For excitations barely above the laser threshold large pulse
      variations are identified as an effect of small variations of the pump parameter.

PMID- 11461383
TI  - Trajectory versus probability density entropy.
AB  - We show that the widely accepted conviction that a connection can be established
      between the probability density entropy and the Kolmogorov-Sinai (KS) entropy is
      questionable. We adopt the definition of density entropy as a functional of a
      distribution density whose time evolution is determined by a transport equation,
      conceived as the only prescription to use for the calculation. Although the
      transport equation is built up for the purpose of affording a picture equivalent
      to that stemming from trajectory dynamics, no direct use of trajectory time
      evolution is allowed, once the transport equation is defined. With this
      definition in mind we prove that the detection of a time regime of increase of
      the density entropy with a rate identical to the KS entropy is possible only in a
      limited number of cases. The proposals made by some authors to establish a
      connection between the two entropies in general, violate our definition of
      density entropy and imply the concept of trajectory, which is foreign to that of
      density entropy.

PMID- 11461384
TI  - Amplitude-free correlation function based on an algebra for coordinate
      transformation in semiclassical integrals.
AB  - We present an algebra that facilitates a systematic coordinate transformation in
      semiclassical integrals such as those between the initial and final value
      representations. Applying this algebra to Maslov-type semiclassical wave packet
      theory [A. Inoue-Ushiyama and K. Takatsuka, Phys. Rev. A 59, 3256 (1999)], a
      semiclassical correlation function is extracted, which is free of the amplitude
      factor that suffers an exponential divergence in a chaotic system.

PMID- 11461385
TI  - Model for interacting instabilities and texture dynamics of patterns.
AB  - A simple model to study interacting instabilities and textures of resulting
      patterns for thermal convection is presented. The model, consisting of a twelve
      mode dynamical system derived for periodic square lattice, describes convective
      patterns in the form of stripes and patchwork quilt. The interaction between
      stationary zigzag stripes and standing patchwork quilt pattern leads to
      spatiotemporal patterns of twisted patchwork quilt. Textures of these patterns,
      which depend strongly on Prandtl number, are investigated numerically using the
      model. The model also shows an interesting possibility of a multicritical point,
      where stability boundaries of four different structures meet.

PMID- 11461386
TI  - Systematic weakly nonlinear analysis of interfacial instabilities in Hele-Shaw
      flows.
AB  - We develop a systematic method to derive all orders of mode couplings in a weakly
      nonlinear approach to the dynamics of the interface between two immiscible
      viscous fluids in a Hele-Shaw cell. The method is completely general: it applies
      to arbitrary geometry and driving. Here we apply it to the channel geometry
      driven by gravity and pressure. The finite radius of convergence of the mode
      coupling expansion is found. Calculation up to third-order couplings is done,
      which is necessary to account for the time-dependent Saffman-Taylor finger
      solution and the case of zero viscosity contrast. The explicit results provide
      relevant analytical information about the role that the viscosity contrast and
      the surface tension play in the dynamics of the system. We finally check the
      quantitative validity of different orders of approximation and a resummation
      scheme against a physically relevant, exact time-dependent solution. The
      agreement between the low-order approximations and the exact solution is
      excellent within the radius of convergence, and is even reasonably good beyond
      this radius.

PMID- 11461387
TI  - Convection patterns in end-heated inclined enclosures.
AB  - The natural convection in inclined side-heated rectangular boxes with adiabatic
      walls is theoretically and numerically investigated. The study is focused on the
      characterization of the convection patterns arising at the core of the basic
      steady unicellular flow and covers the whole range of Prandtl numbers (0< or = Pr
      < or = infinity) and inclinations (from alpha=0 degrees, heated-from-below
      vertical cavities, to alpha=180 degrees ). The onset of the flow instabilities
      depends on the core Rayleigh number R identical with K Ra, defined in terms of
      the local streamwise temperature gradient, K Delta T/L. The critical value of R
      for transversal and longitudinal modes is determined by the linear stability
      analysis of the basic plane-parallel flow, which also provides the stability
      diagram in the (Pr-alpha) chart. Anyhow, the effect of confinement can decisively
      change the stability properties of the core: if the steady unicell reaches the
      boundary layer regime (BLR) the local temperature gradient vanishes at the core
      leaving a completely stable core region. A theoretical determination of the
      frontier of the BLR in the space of parameters (alpha, R, and cavity size) yields
      an extra criterion of stability that has been displayed in the stability diagram.
      As confirmed by numerical calculations, the core-flow instabilities can only
      develop for Pr<O(1) whereas, at larger Pr the core region remains stable and the
      instabilities may only develop at the boundary layers. The analysis of the
      instability mechanisms reveals several couplings between the momentum and
      temperature fields that are not possible in the horizontal (alpha=90 degrees ) or
      vertical limits. For instance, by tilting the cavity with respect to alpha=0
      degrees, the (Rayleigh-Bernard) stationary thermal mode is suppressed in cavities
      whose depth is smaller than a theoretically predicted cutoff wavelength. The
      inclination also alters the properties of the oscillatory longitudinal
      instability, extensively investigated in the horizontal Hadley configuration at
      low Pr (liquid metals). An analytical relationship for its frequency in terms of
      alpha, Ra, and Pr is derived. Throughout the paper, numerical calculations in two
      and three-dimensional enclosures illustrate each type of multicellular flow and
      examples of instability interactions near the codimension-2 lines predicted by
      the theory.

PMID- 11461388
TI  - Local properties of extended self-similarity in three-dimensional turbulence.
AB  - Using a generalization of extended self-similarity we have studied local scaling
      properties of incompressible homogeneous isotropic three-dimensional turbulence
      in a direct numerical simulation. We have found that these properties are
      consistent with log-normal-like behavior of the velocity increments with moderate
      amplitudes for space scales r beginning from Kolmogorov length eta up to the
      largest scales, and in the whole range of the Reynolds numbers: 50 < or =
      R(lambda) < or = 459. The locally determined intermittency exponent mu(r) varies
      with r; it has a maximum at scale r=14 eta, independent of R(lambda).

PMID- 11461389
TI  - Spectral statistics of instantaneous normal modes in liquids and random matrices.
AB  - We study the statistical properties of eigenvalues of the Hessian matrix H
      (matrix of second derivatives of the potential energy) for a classical atomic
      liquid, and compare these properties with predictions for random matrix models.
      The eigenvalue spectra (the instantaneous normal mode or INM spectra) are
      evaluated numerically for configurations generated by molecular dynamics
      simulations. We find that distribution of spacings between nearest-neighbor
      eigenvalues, s, obeys quite well the Wigner prediction s exp(-s(2)), with the
      agreement being better for higher densities at fixed temperature. The deviations
      display a correlation with the number of localized eigenstates (normal modes) in
      the liquid; there are fewer localized states at higher densities that we quantify
      by calculating the participation ratios of the normal modes. We confirm this
      observation by calculating the spacing distribution for parts of the INM spectra
      with high participation ratios, obtaining greater conformity with the Wigner
      form. We also calculate the spectral rigidity and find a substantial dependence
      on the density of the liquid.

PMID- 11461390
TI  - Short wavelength spectrum and Hamiltonian stability of vortex rings.
AB  - We compare dynamical and energetical stability criteria for vortex rings. It is
      argued that vortex rings will be intrinsically unstable against perturbations
      with short wavelengths below a critical wavelength because the canonical vortex
      Hamiltonian is unbounded from below for these modes. To explicitly demonstrate
      this behavior, we derive the oscillation spectrum of vortex rings in
      incompressible, inviscid fluids within a geometrical cutoff procedure for the
      core. The spectrum develops an anomalous branch of negative group velocity and
      approaches the zero of energy for wavelengths that are about six times the core
      diameter. We show the consequences of this dispersion relation for the
      thermodynamics of vortex rings in superfluid 4He at low temperatures.

PMID- 11461391
TI  - Refined scaling hypothesis for breakdown coefficients in turbulence.
AB  - We study the statistics of Novikov's breakdown coefficients, which represent
      ratios between energy dissipation rates at different length scales in turbulence.
      The distribution of their logarithms is shown to be very closely reproduced by an
      analytic function that we obtain from a hierarchical stochastic process for the
      turbulent cascade. Correlations and deviation from Gaussianity in the model are
      accounted for by two parameters, one of which can be interpreted as a generalized
      dimension. Finally, we illustrate the lack of power-law scaling in the moments of
      the breakdown coefficients and propose an analytical approximation scheme for
      them.

PMID- 11461392
TI  - Scalings and structures in turbulent Couette-Taylor flow.
AB  - The scaling of velocity structure functions in Couette-Taylor flow [Lewis and
      Swinney, Phys. Rev. E 59, 5457 (1999)] is revisited to obtain more accurate
      values of the scaling exponents for the Reynolds number range investigated,
      12,000 to 540,000 (Taylor Reynolds numbers, 34<R(lambda)<220). Systematic
      convergence of the statistics with increasing sample size is examined, and the
      uncertainty of the scaling exponents is assessed. At all Reynolds numbers the
      data support the hierarchical symmetry proposed by She and Leveque [Phys. Rev.
      Lett. 72, 336 (1994)]. The She-Leveque constant beta has a value of 0.83,
      indicating greater intermittency in Couette-Taylor turbulence than in free jets,
      where beta=0.87. The constant gamma, which is a measure of the degree of
      singularity of the most intermittent structure, decreases from 0.14 for R<10(5)
      to 0.10 for R>10(5); this transition corresponds to a visually observed break up
      of the Taylor vortex roll structure with increasing R.

PMID- 11461393
TI  - Flow sensitivity and coherence in steady-state free spin precession.
AB  - Steady-state free precession (SSFP) of nuclear spins in the presence of a
      magnetic field gradient is known to be very sensitive to flow. We present a
      theoretical and experimental study of flow sensitivity in a regime where the
      spacing of the radio-frequency pulses is extremely short compared with the free
      induction decay time and the relaxation times. Under these rather drastic
      conditions, a truly continuous wave free precession (CWFP) regime is established,
      in which, unlike standard SSFP, a large degree of coherence is preserved. This
      leads to a quite different flow sensitivity, which is significant even when very
      small magnetic field gradients are present. The unspoiled coherence is predicted
      to cause different flow effects which we confirmed experimentally. Tailored flow
      sensitivity can be achieved by adjusting the frequency offset from resonance,
      which plays a dominant role in the CWFP regime.

PMID- 11461394
TI  - Effect of liquid temperature on sonoluminescence.
AB  - Computer simulations of bubble oscillations are performed under conditions of
      sonoluminescence (SL) in water for various liquid temperatures. It is clarified
      that at almost all acoustic amplitudes, the bubble temperature at the collapse is
      higher in a colder liquid because a lesser amount of water vapor is trapped
      inside a bubble at the collapse due to the lower-saturated vapor pressure.
      Accordingly, at relatively low-acoustic amplitudes, the SL emissions from plasma
      inside a bubble are much stronger in a colder liquid. However, at higher-acoustic
      amplitudes, the SL emission originates in chemiluminescence of OH and the
      intensity is smaller in a colder liquid because a lesser amount of excited OH
      radicals are created inside a bubble. In actual experiments of multibubble
      sonoluminescence (MBSL) in water, the light consists of plasma emissions from low
      acoustic amplitude region and chemiluminescence of OH from high-acoustic
      amplitude region. Usually, MBSL in a colder liquid is stronger because of the
      much stronger plasma emissions. The liquid-temperature dependence of single
      bubble sonoluminescence is also discussed.

PMID- 11461395
TI  - Rayleigh-Marangoni convection in a critical fluid: a tale of two crossovers.
AB  - We show that if we take a thin layer of fluid where surface tension effects are
      supposed to dominate and gradually bring the mean temperature of the layer closer
      and closer to the liquid vapor critical point, then first there is a crossover
      from Marangoni to Rayleigh-Benard convection and thence to a convection whose
      onset is determined by the Schwarzchild criterion.

PMID- 11461396
TI  - Stability of scaling regimes in d > or = 2 developed turbulence with weak
      anisotropy.
AB  - Fully developed turbulence with weak anisotropy is investigated by means of the
      renormalization group approach and double expansion regularization for dimensions
      d > or = 2. Some modification of the standard minimal subtraction scheme has been
      used to analyze the stability of the Kolmogorov scaling regime which is governed
      by the renormalization group fixed point. This fixed point is unstable at d=2;
      thus the infinitesimally weak anisotropy destroys the above scaling regime in two
      dimensional space. The restoration of the stability of this fixed point, under a
      transition from d=2 to 3, is demonstrated at a borderline dimension 2<d(c)<3. The
      results are in qualitative agreement with results recently obtained in the
      framework of a typical analytical regularization scheme.

PMID- 11461397
TI  - Dynamic permeability of electrically conducting fluids under magnetic fields in
      annular ducts.
AB  - The dynamic response of an electrically conducting fluid (either Newtonian or
      Maxwellian) flowing between straight concentric circular cylinders under a
      constant radial magnetic field, is analyzed. The isothermal flow is studied using
      the time Fourier transform, so that the dynamic generalization of Darcy's law in
      the frequency domain is obtained and analytical expressions for the dynamic
      permeability are derived. For the Newtonian case, the range of frequencies where
      the dynamic permeability approaches the static value is enlarged the smaller the
      gap between the cylinders and the higher the magnetic-field strength. For the
      Maxwell fluid, the presence of the inner cylinder shifts the frequencies that
      lead to the enhancement of the real part of the dynamic permeability to larger
      values and increases its maximum values relative to the case where the inner
      cylinder is absent. In addition, the Ohmic dissipation causes the damping of the
      amplitude of the response.

PMID- 11461398
TI  - Turbulence and passive scalar transport in a free-slip surface.
AB  - We consider the two-dimensional (2D) flow in a flat free-slip surface that bounds
      a three-dimensional (3D) volume in which the flow is turbulent. The equations of
      motion for the two-dimensional flow in the surface are neither compressible nor
      incompressible but strongly influenced by the 3D flow underneath the surface. The
      velocity correlation functions in the 2D surface and in the 3D volume scale with
      the same exponents. In the viscous subrange the amplitudes are the same, but in
      the inertial subrange the 2D one is reduced to 2/3 of the 3D amplitude. The
      surface flow is more strongly intermittent than the 3D volume flow. Geometric
      scaling theory is used to derive a relation between the scaling of the velocity
      field and the density fluctuations of a passive scalar advected on the surface.

PMID- 11461399
TI  - Nonlocal Kardar-Parisi-Zhang equation to model interface growth.
AB  - The dynamics of the growth of interfaces in the presence of noise and when the
      normal velocity is constant, in the weakly nonlinear limit, are described by the
      Kardar-Parisi-Zhang (KPZ) equation. In many applications, however, the growth is
      controlled by nonlocal transport, which is not contained in the original KPZ
      equation. For these problems we are proposing an extension of the KPZ model,
      where the nonlocal contribution is expressed through a Hilbert transform and can
      act to either stabilize or destabilize the interface. The model is illustrated
      with a specific example from reactive infiltration. The properties of the
      solution of the resulting equation are studied in one spatial dimension in the
      linear and the nonlinear limits, for both stable and unstable growth. We find
      that the early-time behavior has a power-law scaling similar to that of the KPZ
      equation. However, in the case of stable growth, the scaling of the saturation
      width is logarithmic, which differs from the power law in the KPZ equation. This
      dependence reflects the stabilizing effect of nonlocal transport. In the unstable
      case, we obtain results similar to those of Olami et al. [Phys. Rev. E 55, 2649
      (1997)].

PMID- 11461400
TI  - Effect of gradient production on scalar fluctuations in decaying grid turbulence.
AB  - A generalized form of Yaglom's equation, in which the effect of turbulent
      production of temperature fluctuations is taken into account, is derived. The
      modified Yaglom equation (which extends the work of Danaila et al. [J. Fluid
      Mech. 391, 359 (1999)] to incorporate the effects of decay and production) is
      compared with experimental data. The flow under consideration is decaying grid
      turbulence with an imposed mean temperature gradient (Mydlarski and Warhaft [J.
      Fluid Mech. 358, 135 (1998)]). The agreement between theory and experiment is
      good and the effects of nonhomogeneities in the flow are small.

PMID- 11461401
TI  - Role of gas density in the stability of single-bubble sonoluminescence.
AB  - Recent full hydrodynamic simulations of a sonoluminescing bubble interior have
      shown that the bubble content is compressed to a very dense state during the
      violent collapse. In this paper, we numerically studied the shape stability of a
      radially oscillating gas bubble by using Hilgenfeldt et al. theoretical model
      with corrections taking into account the gas density effect. Our results show
      that gas density variations not only significantly suppress the Rayleigh-Taylor
      instability, but also enhance the threshold of the parametric instability under
      sonoluminescence conditions.

PMID- 11461402
TI  - Control of Rayleigh-Taylor instability by vertical vibration in large aspect
      ratio containers.
AB  - We consider a horizontal heavy fluid layer supported by a light, immiscible one
      in a wide (as compared to depth) container, which is vertically vibrated
      intending to counterbalance the Rayleigh-Taylor instability of the flat, rigid
      body vibrating state. In the simplest case when the density and viscosity of the
      lighter fluid are small compared to their counterparts in the heavier fluid, we
      apply a long wave, weakly nonlinear analysis that yields a generalized Cahn
      Hilliard equation for the evolution of the fluid interface. This equation shows
      that the stabilizing effect of vibration is like that of surface tension, and is
      used to analyze the linear stability of the flat state, the local bifurcation at
      the instability threshold and some global existence and stability properties
      concerning the steady states without dry spots. The analysis is extended to two
      cases of practical interest. Namely, (a) the viscosity of one of the fluids is
      much smaller than that of the other one, and (b) the densities and viscosities of
      both fluids are quite close to each other.

PMID- 11461403
TI  - Tomographic study of helical modes in bifurcating Taylor-Couette-Poiseuille flow
      using magnetic resonance imaging.
AB  - The quantitative visualization of flow in a wide-gap annulus (radius ratio 0.5)
      between concentric cylinders with the inner cylinder rotating and a superimposed
      axial flow reveals a novel mixed-mode state at relatively high flow rates. A fast
      magnetic resonance imaging sequence allows the cinematographic dissection and
      three-dimensional reconstruction of supercritical nonaxisymmetric modes in a
      regime where stationary helical and propagating toroidal vortices coexist. The
      findings shed light on symmetry-breaking instabilities, flow pattern selection,
      and their consequences for hydrodynamic mixing in a complex laminar flow that
      constitutes a celebrated prototype of many mixing or fractionation processes.

PMID- 11461404
TI  - Electron-distribution-function cutoff mechanism in a low-pressure afterglow
      plasma.
AB  - A model is developed for self-consistent simulations of transient phenomena in a
      low-pressure afterglow plasma. The model is based on the nonlocal approach which
      allows a kinetic description of the plasma decay under nonquasistationary
      conditions. Such conditions arise when collisions (mainly electron-electron) are
      not sufficient for the electron distribution function (EDF) to follow changes in
      the self-consistent electric fields and the ion density once the power is turned
      off. As a result, collisions cannot provide the electron and ion particle balance
      by allowing electrons to flow out of the potential well. A cutoff mechanism is
      suggested that provides such a balance during the transient period--from the
      glow, stationary plasma to the quasistationary, afterglow plasma. This mechanism
      is essential for determining correctly the self-consistent wall potential (and
      hence the energy of ions impinging upon the wall surface) and other parameters,
      such as diffusion cooling, which is the most important cooling mechanism at low
      pressures. These phenomena are modeled using the time-dependent nonlocal electron
      Boltzmann equation with a nonlinear electron-electron collision operator. A
      numerical treatment is made by extending Rockwood's method for finite-difference
      discretization of this operator in the total energy formulation. The model
      calculates self-consistently the temporal evolution of the nonlocal EDF and the
      electric potentials in the plasma and the wall sheath. Strongly non-Maxwellian
      EDF's are predicted and it is observed that, depending on plasma conditions, the
      transient period maybe rather long, of order of the ambipolar diffusion time,
      lower pressures resulting in longer transient times. The proposed approach can be
      applied to model self-consistently pulsed plasmas during both the power-on and
      power-off periods, including the breakdown period.

PMID- 11461405
TI  - Nonlinear transports and microvortex excitations in sheared quasi-two-dimensional
      dust Coulomb liquids.
AB  - The microscopic spatiotemporal response of a quasi-two-dimensional dust Coulomb
      liquid to the shear induced by a cw laser is investigated through optical
      microscopy. The dust Coulomb liquid consists of many micrometer sized dust
      particles charged and suspended in a low pressure rf discharge background.
      Assisted by thermal fluctuations, the laser forcing enhances the cascaded
      generation of irregular vortices through reducing caging barriers for collective
      hopping. The vortex mixing leads to the mean velocity field with a simple
      structure that has a strong shear along the edge of the narrow laser beam. It
      also promotes the anomalous transverse diffusion with decaying strength from the
      line source. The viscosity and diffusion coefficient both show nonlinear
      dependence on the laser power under the interplay among the above nonlinear
      excitation and relaxation processes.

PMID- 11461406
TI  - Observation of ultrahigh-energy electrons by resonance absorption of high-power
      microwaves in a pulsed plasma.
AB  - The interaction of high power microwave with collisionless unmagnetized plasma is
      studied. Investigation on the generation of superthermal electrons near the
      critical layer, by the resonance absorption phenomenon, is extended to very high
      microwave power levels (eta=E(2)(0)/4 pi n(e)kT(e) approximately 0.3). Here E0,
      n(e), and T(e) are the vacuum electric field, electron density, and electron
      temperature, respectively. Successive generation of electron bunches having
      maximum energy of about 2 keV, due to nonlinear wave breaking, is observed. The
      electron energy epsilon scales as a function of the incident microwave power P,
      according to epsilon proportional to P0.5 up to 250 kW. The two-dimensional
      spatial distribution of high energy electrons reveals that they are generated
      near the critical layer. However, the lower energy component is again produced in
      the subcritical density region indicating the possibility of other electron
      heating mechanisms.

PMID- 11461407
TI  - Nonlinear propagation of short intense laser pulses in a hollow metallic
      waveguide.
AB  - The propagation of a short intense laser pulse in the femtosecond range in a
      hollow metallic waveguide gives rise to heating of the metallic wall. The
      temperature of the degenerate electron gas in the wall is increased during the
      pulse duration and this heating affects the propagation and dissipation of the
      laser pulse. Analytical and numerical analysis shows that, as the dissipation is
      increased, the leading edge of the pulse decreases more slowly than the rear,
      resulting in a pulse shortening.

PMID- 11461408
TI  - Motion of charged particles near magnetic-field discontinuities.
AB  - Charged particles near discontinuities in magnetic fields, so-called "boundary
      particles," can be constrained to remain near the discontinuity, even an
      arbitrarily fractured discontinuity, as the particle drifts along the fractured
      boundary. These particles are shown to exhibit new and interesting effects along
      broken and branching surfaces, including the wetting of fractured surfaces.

PMID- 11461409
TI  - Dispersion properties of Trivelpiece-Gould waves in periodic plasma waveguides.
AB  - Spectral properties of plasma waves in periodic plasma-filled waveguides are
      analyzed. Unusual features in the spectral behavior and field distribution of
      natural plasma modes are predicted. In particular, it is shown that the plasma
      wave spectrum has a zonal character with allowed and forbidden bands. The
      periodicity strongly distorts the field distribution of plasma waves at
      frequencies near forbidden bands. Due to the significant contribution of higher
      spatial harmonics, the field of the plasma wave concentrates in small regions and
      achieves rather large local values. However, at frequencies far from forbidden
      bands the influence of the periodicity on dispersion properties and field
      distribution of plasma waves is negligible. Possible consequences of these
      effects for the beam-plasma instability in periodic plasma-filled waveguides are
      discussed.

PMID- 11461410
TI  - Spectral properties of small dusty clusters.
AB  - A monolayer dusty crystal can be observed in the glow discharge. In particular, a
      small number of dusty grains form simple atom-like plane clusters. Stability and
      oscillations of the polygonal cluster are considered. For the simplest stable
      clusters normal displacements and frequencies are found for an arbitrary form of
      mutual interaction. The measurement of these modes can help to give in detail the
      form of the potential function.

PMID- 11461411
TI  - Calculations of properties of screened He-like systems using correlated wave
      functions.
AB  - The purpose of the present study is twofold. First, the techniques of correlated
      wave functions for two-electron systems have been extended to obtain results for
      P and D states in a screening environment, and in particular for Debye screening.
      In these calculations, the satisfaction of both the quantum virial theorem and a
      related sum rule has been enforced and found to provide a high degree of
      stability of the solutions. Second, in order to facilitate the general use of
      correlated wave functions in combination with sum rule stability criteria, a
      rather systematic computational approach to this notoriously cumbersome method
      has been developed and thoroughly discussed here. Accurate calculations for few
      electron systems are of interest to plasma diagnostics; in particular, when
      inaccuracies in binding energies are drastically magnified as they occur in
      exponents of Boltzmann factors.

PMID- 11461412
TI  - Dynamical properties and plasmon dispersion of a weakly degenerate correlated one
      component plasma.
AB  - Classical Molecular Dynamics simulations for a one-component plasma are
      presented. Quantum effects are included in the form of the Kelbg potential.
      Results for the dynamical structure factor are compared with the Vlasov and
      random phase approximation theories. The influence of the coupling parameter
      Gamma, degeneracy parameter rho Lambda(3), and the form of the pair interaction
      on the optical plasmon dispersion is investigated. An improved analytical
      approximation for the dispersion of Langmuir waves is presented.

PMID- 11461413
TI  - Non-local-thermodynamical-equilibrium effects in the x-ray emission of
      radiatively heated materials of different atomic numbers.
AB  - X-ray self-emission of radiatively heated materials with different values of Z
      has been investigated. Thin foils were uniformly heated by a 120-eV Hohlraum
      radiation of 400-ps duration in order to study the self-emission of a
      homogeneous, optically thin material. The x-ray emission spectra were followed
      for more than 2 ns. The spectrally integrated emission shows not only a strong Z
      dependence, but different temporal behaviors for different values of Z. The lower
      is the value of Z of the x-ray heated matter, the longer is the duration of self
      emission. Theoretical comparison with a hydrocode and FLY post-processing shows a
      non-local-thermal equilibrium behavior caused by direct photoionization due to
      the thermal pumping radiation, which has a higher brightness temperature than the
      matter temperature of the heated material.

PMID- 11461414
TI  - Transport of ground-state hydrogen atoms in a plasma expansion.
AB  - The transport of ground-state atomic hydrogen in the expansion of a thermal
      plasma generated from an Ar-H2 mixture is studied by means of laser-based
      diagnostic techniques. The flow of hydrogen atoms is investigated by two-photon
      excitation laser-induced fluorescence (LIF), whereas Ar atoms are probed by LIF
      as well as by UV Rayleigh scattering. The transport of Ar atoms can be fully
      understood in terms of a free jet flow; H atoms on the contrary exhibit an
      anomalous behavior. In the course of the plasma expansion, hydrogen atoms
      decouple from the argon fluid by a diffusion process as a direct consequence of
      recombination of H atoms at the vessel walls. In this contribution it is shown,
      on the basis of experimental results, how plasma-surface interactions can
      strongly influence the flow pattern of an atomic radical fluid.

PMID- 11461415
TI  - Multifilament structures in relativistic self-focusing.
AB  - A simple model is derived to prove the multifilament structure of relativistic
      self-focusing with ultraintense lasers. Exact analytical solutions describing the
      transverse structure of waveguide channels with electron cavitation, for which
      both the relativistic and ponderomotive nonlinearities are taken into account,
      are presented.

PMID- 11461416
TI  - Microscopic and macroscopic aspects of stick-slip motion in granular shear.
AB  - An annular shear cell has been used to investigate a number of factors known to
      influence stick-slip motion in an assembly of near monosized, spherical glass
      beads. In this paper, both the sample shear stress and volumetric strain were
      recorded, allowing new insights into the possible mechanics of stick-slip motion
      in a granular body. Rather than the commonly presented mechanism of sample
      dilation and fluidization accompanying the slip events, in the material studied
      here, sample dilation occurred during the preslip deformations of the granular
      body, while the slip event was accompanied by assembly contraction. Drive
      velocity and applied normal pressure were both found to influence the magnitude
      of the stick-slip spikes in a manner analogous to previous studies of stick-slip
      in assemblies of confined, near-spherical lubricant systems. Finally, atmospheric
      relative humidity was found to have a marked effect on the magnitude of the stick
      slip motion. To investigate this mechanism more fully, the atomic force
      microscopy was employed to measure the particle-particle interaction forces as a
      function of atmospheric relative humidity. A water meniscus was found to form
      under all humidities, from less than 5% to greater than 95%. However, its
      influence on the adhesive forces varied by an order of magnitude. While most
      previous studies of stick-slip phenomena have attempted to remove atmospheric
      humidity as a variable, here we present a useful link between the role of
      relative humidity on particle-particle interaction forces and the macroscopic
      response of the granular assembly.

PMID- 11461417
TI  - Neutron energy spectra from the laser-induced Dd,n3He reaction.
AB  - Detailed neutron energy spectra were measured for the D(d,n)3He reaction induced
      in solid (CD2)(n) targets by irradiation with 50-fs 2 x 10(18) W/cm(2) light
      pulses from a 10-TW Ti:Sapphire laser. The neutrons were observed at two angles 5
      degrees and 112 degrees relative to the incident laser beam. The neutron spectra
      at the two angles are characterized by peaks with large widths of about 700 keV
      full width at half maximum and a shift of 300 keV between them. Neutron energies
      of up to about 4 MeV were observed indicating that deuterons are accelerated up
      to an energy of 1 MeV in the laser produced plasma. Simulation calculations can
      describe qualitatively the neutron spectra by assuming isotropic deuteron
      acceleration and a reduction of the reaction probability by a factor of 1/3 for
      deuterons emitted from the front of the target. These calculations indicate in
      particular that it is necessary to assume deuterons moving both into and out of
      the front of the target in order to describe the neutron energy spectra at the
      two angles. The highest recorded mean neutron yield was about 10(4) neutrons per
      pulse. The neutron yield increases with the number of electrons emitted from the
      front of the target and with the intensity of the prompt gamma flash induced by
      the bremsstrahlung of energetic electrons.

PMID- 11461418
TI  - Three-dimensional singularities of a thin plasma slab.
AB  - The three-dimensional (3D) nonlinear development of the interchange-like
      (Rayleigh-Taylor) instability of a thin slab of plasma exhibits interesting
      features with respect to its two-dimensional (2D) limit investigated by Bulanov,
      Pegoraro, and Sakai [Phys. Rev. E 59, 2292 (1999)]. We show that, contrary to the
      2D case, the 3D evolution equations remain nonlinear when Lagrangian variables
      are adopted. Explicit solutions are found by the use of a generalized hodograph
      transformation. Both compression and rarefaction singularities are formed. Local
      solutions in the neighborhood of the singular points have a generic 2D character.

PMID- 11461419
TI  - Decompressive (cooling rarefaction) shock in optically thin radiative plasma.
AB  - It is shown that the decompressive shock, i.e., a shock where the pressure behind
      the front is smaller than the pressure ahead of it, is possible in a radiative
      plasma; this is in contrast to the situation in classic gas dynamics. An example
      of a steady state decompressive shock wave for a simple, but realistic model for
      radiative losses is presented. It is shown that it satisfies the Landau stability
      criteria.

PMID- 11461420
TI  - Three-dimensional theory of emittance in Compton scattering and x-ray protein
      crystallography.
AB  - A complete, three-dimensional theory of Compton scattering is described, which
      fully takes into account the effects of the electron beam emittance and energy
      spread upon the scattered x-ray spectral brightness. The radiation scattered by
      an electron subjected to an arbitrary electromagnetic field distribution in
      vacuum is first derived in the linear regime, and in the absence of radiative
      corrections; it is found that each vacuum eigenmode gives rise to a single
      Doppler-shifted classical dipole excitation. This formalism is then applied to
      Compton scattering in a three-dimensional laser focus, and yields a complete
      description of the influence of the electron beam phase-space topology on the x
      ray spectral brightness; analytical expressions including the effects of
      emittance and energy spread are also obtained in the one-dimensional limit.
      Within this framework, the x-ray brightness generated by a 25 MeV electron beam
      is modeled, fully taking into account the beam emittance and energy spread, as
      well as the three-dimensional nature of the laser focus; its application to x-ray
      protein crystallography is outlined. Finally, coherence, harmonics, and radiative
      corrections are also briefly discussed.

PMID- 11461421
TI  - Synchrotron-betatron coupling due to monochromatization.
AB  - The effects of large dispersion at the interaction point are discussed within the
      linear approximation of the beam-beam force. The synchrotron and betatron motions
      affect each other. Synchrotron and betatron tune shifts as well as bunch-length
      and energy-spread modifications appear, among many effects. Depending on the
      parameters, degradations of the luminosity can occur due to the hourglass effect.
      More serious is an enlargement of the collision energy spread, which may reduce
      the event rate and invalidate the monochromatization scheme.

PMID- 11461422
TI  - Breakdown of a conservation law in incommensurate systems.
AB  - We show that invariance properties of the Lagrangian of an incommensurate system,
      as described by the Frenkel-Kontorova model, imply the existence of a generalized
      angular momentum that is an integral of motion if the system remains floating.
      The behavior of this quantity can therefore monitor the character of the system
      as floating (when it is conserved) or locked (when it is not). We find that,
      during the dynamics, the nonlinear couplings of our model cause parametric phonon
      excitations that lead to the appearance of Umklapp terms and to a sudden
      deviation of the generalized momentum from a constant value, signaling a
      dynamical transition from a floating to a pinned state. We point out that this
      transition is related but does not coincide with the onset of sliding friction,
      which can take place when the system is still floating.

PMID- 11461423
TI  - Breaking of time reversal invariance in nonlinear acoustics.
AB  - Time-reversal invariance of nonlinear acoustic wave propagation is experimentally
      investigated. Reversibility is studied for propagation shorter or longer than
      shock formation distance. In the first case, time-reversal invariance holds and a
      sinusoid distorted by nonlinearities during forward propagation progressively
      recovers its initial shape after the time-reversal operation. In the second case,
      reversibility is broken locally at the shock front as a time-reversal operation
      transforms a stable compression shock into an unstable expansion shock. Achieving
      experimentally the time-reversal process with a time-reversal mirror made of
      reversible piezoelectric transducers for very broadband signals, would require
      transducers with huge bandwidths. To date, such transducers remain unavailable.
      In order to overcome this technical limitation, we restricted ourselves in this
      study to one-dimensional (1D) propagation, for which an experimental ersatz of a
      time-reversal mirror can be used. Indeed, in a 1D case, the time-reversal
      operation applied on a plane wave can be mimicked for an antisymmetric wave form
      by a reflection of the plane wave onto a pressure-release interface.

PMID- 11461424
TI  - Traveling solitons in the parametrically driven nonlinear Schrodinger equation.
AB  - We show that the (undamped) parametrically driven nonlinear Schrodinger equation
      has wide classes of traveling soliton solutions, some of which are stable. For
      small driving strengths stable nonpropagating and moving solitons co-exist while
      strongly forced solitons can only be stable when moving sufficiently fast.

PMID- 11461425
TI  - Coupling of impurity modes in one-dimensional periodic systems.
AB  - One-dimensional periodic dielectric structures are known to exhibit band gaps
      because of their symmetry. Defect states can be found in the band gaps if an
      impurity layer is added to the lattice such that the symmetry of the structure is
      broken. In this paper, we consider the case where a second impurity layer is
      added and we discuss the existence of coupling between the two defects. We
      discuss the possibility of exploiting the coupling of impurity modes in the
      realization of tunable wavelength emitting devices and dual-wavelength vertical
      cavity surface-emitting lasers.

PMID- 11461426
TI  - Resonant effects in periodic gratings comprising a finite number of grooves in
      each period.
AB  - We give numerical evidence of a kind of resonance that appears in infinite
      perfectly conducting gratings comprising a finite number of grooves in each
      period when illuminated by a normally incident p-polarized plane wave. This
      phenomenon is intimately connected with the particular distribution of the phase
      of the electromagnetic field inside the cavities, which is automatically
      generated by waves of certain resonant wavelengths. The resonances appear as
      sharp peaks in the specularly reflected efficiency and are accompanied by a
      significant intensification of the interior field. We study the particular case
      of rectangular cavities and consider configurations with different numbers of
      grooves per period. The diffraction problem is solved for s and p polarization by
      using the modal method, which proves to be especially suitable for this profile.

PMID- 11461427
TI  - Unusual 1/r-dependent radiation intensity in any biaxial crystal.
AB  - Lighthill's prediction of an unusual 1/r-dependent radiation intensity from a
      small monochromatic source is found to exist in any homogeneous and lossless
      biaxial crystal along the two optical ray axes, where r is the radial distance
      from the source. This is a consequence of the special shape of the wave-vector
      surface on which there is, around each singular point of self-intersection (or
      "dimple"), a circular locus of points all having the same surface normal
      direction and thus sharing a common tangent plane. A heuristic derivation of the
      result is given and a simple optical experiment is proposed to detect such an
      unusual distance dependence.

PMID- 11461428
TI  - Interaction of two one-dimensional Bose-Einstein solitons: chaos and energy
      exchange.
AB  - We analyze the bright soliton interactions of a Bose-Einstein condensate in quasi
      one-dimensional traps putting an emphasis on integrability break down due to a
      trapping potential. In particular, we derive a simple analytical model, which
      describes well all major features of soliton dynamics including chaos and energy
      exchange between interacting solitons induced by the trapping potential.

PMID- 11461429
TI  - Collective variable theory for optical solitons in fibers.
AB  - We present a projection-operator method to express the generalized nonlinear
      Schrodinger equation for pulse propagation in optical fibers, in terms of the
      pulse parameters, called collective variables, such as the pulse width,
      amplitude, chirp, and frequency. The collective variable (CV) equations of motion
      are derived by imposing a set of constraints on the CVs to minimize the soliton
      dressing during its propagation. The lowest-order approximation of this CV
      approach is shown to be equivalent to the variational Lagrangian method. Finally,
      we demonstrate the application of this CV theory for pulse propagation in
      dispersion-managed optical fiber links.

PMID- 11461430
TI  - Photonic band edge effects in finite structures and applications to chi 2
      interactions.
AB  - Using the concept of an effective medium, we derive coupled mode equations for
      nonlinear quadratic interactions in photonic band gap structures of finite
      length. The resulting equations reveal the essential roles played by the density
      of modes and effective phase matching conditions necessary for the strong
      enhancement of the nonlinear response. Our predictions find confirmation in an
      experimental demonstration of significant enhancement of second harmonic
      generation near the photonic band edge. The measured conversion efficiency is in
      good agreement with the conversion efficiency predicted by the effective-medium
      model.

PMID- 11461431
TI  - Soliton interaction in a nonlinear waveguide in the presence of resonances.
AB  - The simultaneous propagation of two optical pulses through a nonlinear dispersive
      medium composed of a resonant three-level system is investigated. By choosing a
      soliton of area 4 pi and order N=2 at the pump frequency, together with a weaker
      pulse with a sech profile at the signal frequency, we show that the pump soliton
      breaks up into a pair of solitary waves which are cloned to the signal frequency.
      Due to a combination of coherent population trapping and nonlinear dispersive
      effects, the pair interacts in a repulsive fashion so that the taller wave
      travels faster than the shorter one.

PMID- 11461432
TI  - Analysis of optical pulse propagation with two-by-two (ABCD) matrices.
AB  - We review and extend the analogies between Gaussian pulse propagation and
      Gaussian beam diffraction. In addition to the well-known parallels between pulse
      dispersion in optical fiber and cw beam diffraction in free space, we review
      temporal lenses as a way to describe nonlinearities in the propagation equations,
      and then introduce further concepts that permit the description of pulse
      evolution in more complicated systems. These include the temporal equivalent of a
      spherical dielectric interface, which is used by way of example to derive design
      parameters used in a recent dispersion-managed soliton transmission experiment.
      This formalism offers a quick, concise, and powerful approach to analyzing a
      variety of linear and nonlinear pulse propagation phenomena in optical fibers.

PMID- 11461433
TI  - Modulational instability in nonlocal nonlinear Kerr media.
AB  - We study modulational instability (MI) of plane waves in nonlocal nonlinear Kerr
      media. For a focusing nonlinearity we show that, although the nonlocality tends
      to suppress MI, it can never remove it completely, irrespective of the particular
      profile of the nonlocal response function. For a defocusing nonlinearity the
      stability properties depend sensitively on the response function profile: for a
      smooth profile (e.g., a Gaussian) plane waves are always stable, but MI may occur
      for a rectangular response. We also find that the reduced model for a weak
      nonlocality predicts MI in defocusing media for arbitrary response profiles, as
      long as the intensity exceeds a certain critical value. However, it appears that
      this regime of MI is beyond the validity of the reduced model, if it is to
      represent the weakly nonlocal limit of a general nonlocal nonlinearity, as in
      optics and the theory of Bose-Einstein condensates.

PMID- 11461434
TI  - Dynamics of a semiconductor laser array with delayed global coupling.
AB  - We study the dynamics of an array of single mode semiconductor lasers globally
      but weakly coupled by a common external feedback mirror and by nearest neighbor
      interactions. We seek to determine the conditions under which all lasers of the
      array are in phase, whether in a steady, periodic, quasiperiodic, or chaotic
      regime, in order to maximize the output far field intensity. We show that the
      delay may be a useful control parameter to achieve in-phase synchronization. For
      the in-phase steady state, there is a competition between a delay-induced Hopf
      bifurcation leading to an in-phase periodic regime and a delay-independent Hopf
      bifurcation leading to an antiphased periodic regime. Both regimes are described
      analytically and secondary Hopf bifurcations to quasiperiodic solutions are
      found. Close to the stable steady state, the array is described by a set of
      Kuramoto equations for the phases of the fields. Above the first Hopf
      bifurcation, these equations are generalized by the addition of second and third
      order time derivatives of the phases.

PMID- 11461435
TI  - Three-dimensional hybrid solitary waves: transverse vortex solitons stabilized by
      longitudinal parametric solitary waves.
AB  - We show that the parametric process in quadratic nonlinear media supports three
      dimensional (3D) hybrid solitary wave solution in which a transverse vortex
      solitons embedded in an infinite plane-wave background is sustained by a
      longitudinal parametric solitary wave. The structure of the parametric solitary
      wave results from the interplay of the quadratic nonlinearity and the temporal
      walk off (i.e., the velocity mismatch) between the interacting waves. The 3D
      hybrid solitary wave proved to be robust with respect to modulational
      instability, a feature that contrasts with previous studies on quadratic vortex
      solitons that revealed them to be always modulationally unstable. We show that
      the mechanism of stabilization of the vortex background lies on the temporal
      walkoff between the interacting waves that is able to drift the modulational
      instability out of the temporally localized structure that constitutes the 3D
      hybrid solitary wave.

PMID- 11461436
TI  - Approximating the number of monomer-dimer coverings in periodic lattices.
AB  - Our starting point is an algorithm of Kenyon, Randall, and Sinclair, which is
      built upon the ideas of Jerrum and Sinclair, giving an approximation to crucial
      parameters of the monomer-dimer covering problem in polynomial time. We make two
      key improvements to their algorithm: we greatly reduce the number of simulations
      that must be run by estimating good values of the generating function parameter,
      and we greatly reduce the number of steps that must be taken in each simulation
      by aggregating to a simulation with at most five states. The result is an
      algorithm that is computationally feasible for modestly sized meshes. We use our
      algorithm on two- and three-dimensional problems, computing approximations to the
      coefficients of the generating function and some limiting values.

PMID- 11461437
TI  - Twist-averaged boundary conditions in continuum quantum Monte Carlo algorithms.
AB  - We develop and test Quantum Monte Carlo algorithms that use a"twist" or a phase
      in the wave function for fermions in periodic boundary conditions. For metallic
      systems, averaging over the twist results in faster convergence to the
      thermodynamic limit than periodic boundary conditions for properties involving
      the kinetic energy and has the same computational complexity. We determine
      exponents for the rate of convergence to the thermodynamic limit for the
      components of the energy of coulomb systems. We show results with twist averaged
      variational Monte Carlo on free particles, the Stoner model and the electron gas
      using Hartree-Fock, Slater-Jastrow, and three-body and backflow wave function. We
      also discuss the use of twist averaging in the grand canonical ensemble, and
      numerical methods to accomplish the twist averaging.

PMID- 11461438
TI  - Semirelativistic Lagrange mesh calculations.
AB  - The Lagrange mesh method is a very powerful procedure to compute eigenvalues and
      eigenfunctions of nonrelativistic Hamiltonians. The trial eigenstates are
      developed in a basis of well-chosen functions and the computation of Hamiltonian
      matrix elements requires only the evaluation of the potential at grid points. It
      is shown that this method can be used to solve semirelativistic two-body
      eigenvalue equations. As in the nonrelativistic case, it is very accurate, fast,
      and very simple to implement.

PMID- 11461439
TI  - Quantum Monte Carlo method for attractive Coulomb potentials.
AB  - Starting from an exact lower bound on the imaginary-time propagator, we present a
      path-integral quantum Monte Carlo method that can handle singular attractive
      potentials. We illustrate the basic ideas of this quantum Monte Carlo algorithm
      by simulating the ground state of hydrogen and helium.

PMID- 11461440
TI  - Vertical density matrix algorithm: a higher-dimensional numerical renormalization
      scheme based on the tensor product state ansatz.
AB  - We present a new algorithm to calculate the thermodynamic quantities of three
      dimensional (3D) classical statistical systems, based on the ideas of the tensor
      product state and the density matrix renormalization group. We represent the
      maximum-eigenvalue eigenstate of the transfer matrix as the product of local
      tensors that are iteratively optimized by the use of the "vertical density
      matrix" formed by cutting the system along the transfer direction. This
      algorithm, which we call vertical density matrix algorithm (VDMA), is
      successfully applied to the 3D Ising model. Using the Suzuki-Trotter
      transformation, we can also apply the VDMA to 2D quantum systems, which we
      demonstrate for the 2D transverse field Ising model.

PMID- 11461441
TI  - Fast Monte Carlo algorithm for site or bond percolation.
AB  - We describe in detail an efficient algorithm for studying site or bond
      percolation on any lattice. The algorithm can measure an observable quantity in a
      percolation system for all values of the site or bond occupation probability from
      zero to one in an amount of time that scales linearly with the size of the
      system. We demonstrate our algorithm by using it to investigate a number of
      issues in percolation theory, including the position of the percolation
      transition for site percolation on the square lattice, the stretched exponential
      behavior of spanning probabilities away from the critical point, and the size of
      the giant component for site percolation on random graphs.

PMID- 11461442
TI  - Full velocity difference model for a car-following theory.
AB  - In this paper, we present a full velocity difference model for a car-following
      theory based on the previous models in the literature. To our knowledge, the
      model is an improvement over the previous ones theoretically, because it
      considers more aspects in car-following process than others. This point is
      verified by numerical simulation. Then we investigate the property of the model
      using both analytic and numerical methods, and find that the model can describe
      the phase transition of traffic flow and estimate the evolution of traffic
      congestion.

PMID- 11461443
TI  - Reaction front structure in the diffusion-limited A+B model with initially
      randomized reactants.
AB  - Subtle features of the reaction front formation in the A+B-->0 reaction are
      reported for the initially random and equal A+B reactant distribution. Three
      nonclassical parameters (initial linewidth, minimum, and maximum), for each
      interparticle gap and nearest neighbor distance distributions, are derived, as a
      function of time, using Monte Carlo simulations. These empirical front measures
      and their temporal scaling exponents are compared with the previously studied
      ones for the reactant interparticle distributions.

PMID- 11461444
TI  - Shape stability of sonoluminescence bubbles: comparison of theory to experiments.
AB  - Single bubble sonoluminescence (SBSL) is the brief flash of light emitted from a
      single, stable, acoustically forced bubble. In experiments, the maximum pressure
      amplitude with which a bubble may be forced is limited by considerations of
      spherical stability. The traditional linear stability analysis predicts a
      threshold for SBSL at a much lower pressure amplitude than experimental
      observations. This work shows that if one constructs an accurate model of the
      radial dynamics, the traditional linear stability analysis predicts a boundary
      that is in excellent agreement with experimental data.

PMID- 11461445
TI  - Image charge effects on electron capture by dust grains in dusty plasmas.
AB  - Electron-capture processes by negatively charged dust grains from hydrogenic ions
      in dusty plasmas are investigated in accordance with the classical Bohr-Lindhard
      model. The attractive interaction between the electron in a hydrogenic ion and
      its own image charge inside the dust grain is included to obtain the total
      interaction energy between the electron and the dust grain. The electron-capture
      radius is determined by the total interaction energy and the kinetic energy of
      the released electron in the frame of the projectile dust grain. The classical
      straight-line trajectory approximation is applied to the motion of the ion in
      order to visualize the electron-capture cross section as a function of the impact
      parameter, kinetic energy of the projectile ion, and dust charge. It is found
      that the image charge inside the dust grain plays a significant role in the
      electron-capture process near the surface of the dust grain. The electron-capture
      cross section is found to be quite sensitive to the collision energy and dust
      charge.

PMID- 11461446
TI  - Limiting current density in a crossed-field nanogap.
AB  - Using a mean-field theory, we have studied the quantum extension on the limiting
      current density in a crossed-field nanogap. When the gap spacing is less than the
      electron wavelength, our results show that the limiting current density is
      increased by a large factor from the classical values due to the effects of
      electron tunneling. The effects of the external magnetic field diminish with a
      decrease of gap spacing. Smooth transition from the classical regime to the
      quantum regime is demonstrated.

PMID- 11461447
TI  - Comment on "Ward identities for transport of classical waves in disordered
      media".
AB  - Recently Nieh et al. [Phys. Rev. E 57, 1145 (1998)] have considered a version of
      derivation of the Ward identities for scalar and vector classical wave field
      propagation in random media and noted that their results are in contradiction
      with those obtained by Barabanenkov and Ozrin [Phys. Lett. A 154, 38 (1991)]. In
      this Comment we show that the derivation given by Nieh et al. is based on an
      incorrect equation for the energy-vertex function where the term that takes into
      account the contributions of the scatterer polarization to the field energy is
      lost. Restoring this term removes the above-noted contradiction.

PMID- 11461449
TI  - Dark-bright solitons in inhomogeneous Bose-Einstein condensates.
AB  - We investigate dark-bright vector solitary wave solutions to the coupled
      nonlinear Schrodinger equations which describe an inhomogeneous two-species Bose
      Einstein condensate. While these structures are well known in nonlinear fiber
      optics, we show that spatial inhomogeneity strongly affects their motion,
      stability, and interaction, and that current technology suffices for their
      creation and control in ultracold trapped gases. The effect of controllably
      different interparticle scattering lengths is examined, and stability against
      three-dimensional deformations is considered.

PMID- 11461450
TI  - 1/2-anyons in small atomic Bose-Einstein condensates.
AB  - We discuss a way of creating, manipulating, and detecting anyons in rotating Bose
      Einstein condensates consisting of a small number of atoms. By achieving a
      quasidegeneracy in the atomic motional states we drive the system into a 1/2
      Laughlin state for fractional quantum Hall bosons. Localized 1/2-quasiholes can
      be created by focusing lasers at the desired positions. We show how to manipulate
      these quasiholes in order to probe directly their 1/2-statistics.

PMID- 11461451
TI  - "All versus nothing" inseparability for two observers.
AB  - A recent proof of Bell's theorem without inequalities [A. Cabello, Phys. Rev.
      Lett. 86, 1911 (2001)] is formulated as a Greenberger-Horne-Zeilinger-type proof
      involving just two observers. On one hand, this new approach allows us to derive
      an experimentally testable Bell inequality which is violated by quantum
      mechanics. On the other hand, it leads to a new state-independent proof of the
      Kochen-Specker theorem and provides a wider perspective on the relations between
      the major proofs of no hidden variables.

PMID- 11461452
TI  - All-optical formation of an atomic Bose-Einstein condensate.
AB  - We have created a Bose-Einstein condensate (BEC) of 87Rb atoms directly in an
      optical trap. We employ a quasielectrostatic dipole force trap formed by two
      crossed CO2 laser beams. Loading directly from a sub-Doppler laser-cooled cloud
      of atoms results in initial phase space densities of approximately 1/200.
      Evaporatively cooling through the BEC transition is achieved by lowering the
      power in the trapping beams over approximately 2 s. The resulting condensates are
      F = 1 spinors with 3.5x10(4) atoms distributed between the m(F) = (-1,0,1)
      states.

PMID- 11461453
TI  - Nonuniversal behavior of the k-body embedded Gaussian unitary ensemble of random
      matrices.
AB  - Using a novel approach, we investigate the shape of the average spectrum and the
      spectral fluctuations of the k-body embedded unitary ensemble in the limit of a
      large matrix dimension. We identify the transition point between a semicircle and
      a Gaussian shape. The transition also affects the spectral fluctuations which
      deviate from the Wigner-Dyson form and become Poissonian in the limit k<<m<<l.
      Here m is the number of fermions and l the number of degenerate single-particle
      states.

PMID- 11461454
TI  - Giant acceleration of free diffusion by use of tilted periodic potentials.
AB  - The effective diffusion coefficient for the overdamped Brownian motion in a
      tilted periodic potential is calculated in closed analytical form. Universality
      classes and scaling properties for weak thermal noise are identified near the
      threshold tilt where deterministic running solutions set in. In this regime the
      diffusion may be greatly enhanced, as compared to free thermal diffusion with,
      for a realistic experimental setup, an enhancement of up to 14 orders of
      magnitude.

PMID- 11461455
TI  - Deterministic walks in random media.
AB  - Deterministic walks over a random set of N points in one and two dimensions ( d =
      1,2) are considered. Points ("cities") are randomly scattered in R(d) following a
      uniform distribution. A walker ("tourist"), at each time step, goes to the
      nearest neighbor city that has not been visited in the past tau steps. Each
      initial city leads to a different trajectory composed of a transient part and a
      final p-cycle attractor. Transient times (for d = 1,2) follow an exponential law
      with a tau-dependent decay time but the density of p cycles can be approximately
      described by D(p)proportional to p(-alpha(tau)). For tau>>1 and tau/N<<1, the
      exponent is independent of tau. Some analytical results are given for the d = 1
      case.

PMID- 11461456
TI  - Noncommutativity in space and primordial magnetic field.
AB  - In this paper we show that noncommutativity in spatial coordinates can generate
      magnetic field in the early Universe on a horizon scale. The strength of such a
      magnetic field depends on the number density of massive charged particles present
      at a given moment. This allows us to trace back the temperature dependence of the
      noncommutativity scale from the bounds on primordial magnetic field coming from
      nucleosynthesis.

PMID- 11461457
TI  - Dynamics of symmetry breaking and tachyonic preheating.
AB  - We reconsider the old problem of the dynamics of spontaneous symmetry breaking
      (SSB) using 3D lattice simulations. We develop a theory of tachyonic preheating,
      which occurs due to the spinodal instability of the scalar field. Tachyonic
      preheating is so efficient that SSB typically completes within a single
      oscillation as the field rolls towards the minimum of its effective potential. We
      show that, contrary to previous expectations, preheating in hybrid inflation is
      typically tachyonic. Our results may also be relevant for the theory of the
      formation of topological defects and of disoriented chiral condensates in heavy
      ion collisions.

PMID- 11461458
TI  - Supertubes.
AB  - It is shown that a IIA superstring carrying D0-brane charge can be "blown up," in
      a Minkowski vacuum background, to a (1/4)-supersymmetric tubular D2-brane,
      supported against collapse by the angular momentum generated by crossed electric
      and magnetic Born-Infeld fields. This "supertube" can be viewed as a world-volume
      realization of the sigma-model Q lump.

PMID- 11461459
TI  - Model of soft CP violation using scalars with quark number two.
AB  - We propose a model of soft CP violation that evades the strong CP problem and can
      describe observed CP violation in the neutral kaon sector, both direct and
      indirect. Our model requires two "duark" mesons carrying quark number two that
      have complex (CP-violating) bare masses and are coupled to quark pairs. Aside
      from the existence of these potentially observable new particles with masses of
      several hundred GeV, we predict a flat unitarity triangle (i.e., no observable
      direct CP violation in the B-meson sector) and a possibly anomalous branching
      ratio for the decay mode K+-->pi(+)+nu(nu).

PMID- 11461460
TI  - Neutrino mass, muon anomalous magnetic moment, and lepton flavor nonconservation.
AB  - If the generating mechanism for neutrino mass is to account for both the newly
      observed muon anomalous magnetic moment as well as the present experimental
      bounds on lepton flavor nonconservation, then the neutrino mass matrix should be
      almost degenerate and the underlying physics should be observable at future
      colliders. We illustrate this assertion with two specific examples, and show that
      gamma(mu;-->egamma)/m5(mu), gamma(tau-->egamma)/m5tau, and gamma(tau-
      >(mu)gamma)/m5tau are in the ratio ((Delta)m2)2sol/2, ((Delta)m2)2sol/2, and
      ((Delta)m2)2atm, respectively, where the (Delta)m2 parameters are those of solar
      and atmospheric neutrino oscillations and bimaximal mixing has been assumed.

PMID- 11461461
TI  - Strange quark polarization of the nucleon: a parameter-independent prediction of
      the chiral potential model.
AB  - We perform a one-loop calculation of the strange quark polarization (Deltas) of
      the nucleon in an SU(3) chiral potential model. We find that if the intermediate
      quark excited states are summed over in a proper way, i.e., summed up to a given
      energy instead of given radial and orbital quantum numbers, Deltas turns out to
      be almost independent of all the model parameters: quark masses and potential
      strengths. The contribution from the quark-antiquark pair creation and
      annihilation " Z" diagrams is found to be significant. Our numerical results
      agree quite reasonably with experiments and lattice QCD calculations.

PMID- 11461462
TI  - Expansion of bound-state energies in powers of m/M.
AB  - We describe a new approach to computing energy levels of a nonrelativistic bound
      state of two constituents with masses M and m, by a systematic expansion in
      powers of m/M. After discussing the method, we demonstrate its potential with an
      example of the radiative recoil corrections to the Lamb shift and hyperfine
      splitting relevant for the hydrogen, muonic hydrogen, and muonium. A discrepancy
      between two previous calculations of O(alpha(Zalpha)5m2/M) radiative recoil
      corrections to the Lamb shift is resolved and several new terms of
      O(alpha(Zalpha)5m4/M3) and higher are obtained.

PMID- 11461463
TI  - Photoelectron diffraction mapping: molecules illuminated from within.
AB  - We demonstrate the use of a multiparticle coincidence technique to image the
      diffraction of an electron wave whose source is placed at a specific site in a
      free molecule. Core-level photoelectrons are used to illuminate the molecule from
      within. By measuring the vector momenta of two molecular fragments and the
      photoelectron, a richly structured electron diffraction pattern is obtained in a
      body-fixed frame of the randomly oriented molecule in the gas phase. We
      illustrate this technique for CO, creating a photoelectron from the C(1s) shell
      and scanning its energy from zero to 30 eV.

PMID- 11461464
TI  - Model-free determination of dissociation energies of polyatomic systems.
AB  - We describe and apply a new procedure that allows a direct determination of
      dissociation energies of polyatomic systems (clusters, fullerenes, polymers, and
      other molecules) without any modeling of the systems under investigation. As an
      example, we have determined the dissociation energies of a series of gold
      clusters Au(+)n. A comparison with values obtained from statistical models of
      unimolecular dissociation shows that these models significantly fail to describe
      the data. In contrast, the new method yields values which are an order of
      magnitude more accurate, thus allowing one to experimentally set benchmarks for
      any theory which attempts to describe activated processes.

PMID- 11461465
TI  - Generation of broadband VUV light using third-order cascaded processes.
AB  - We report the first demonstration of broadband VUV light generation through
      cascaded nonlinear wave mixing in a gas. Using a hollow-fiber geometry to achieve
      broad-bandwidth phase-matching, frequency conversion of ultrashort-pulse
      Ti:sapphire laser pulses from the visible into the deep UV around 200 and 160 nm
      is achieved. A new type of quasi-phase-matching is also observed in the VUV for
      the first time. Conversion using cascaded processes exhibits higher efficiencies,
      shorter pulse durations, and broader bandwidths than other schemes for generating
      light in the deep UV, and will enable many applications in science and
      technology.

PMID- 11461466
TI  - Two-photon diffraction and quantum lithography.
AB  - We report a proof-of-principle experimental demonstration of quantum lithography.
      Utilizing the entangled nature of a two-photon state, the experimental results
      have beaten the classical diffraction limit by a factor of 2. This is a quantum
      mechanical two-photon phenomenon but not a violation of the uncertainty
      principle.

PMID- 11461467
TI  - Quantum fractal fluctuations.
AB  - We numerically analyze quantum survival probability fluctuations in an open,
      classically chaotic system. In a quasiclassical regime and in the presence of
      classical mixed phase space, such fluctuations are believed to exhibit a fractal
      pattern, on the grounds of semiclassical arguments. In contrast, we work in a
      classical regime of complete chaoticity and in a deep quantum regime of strong
      localization. We provide evidence that fluctuations are still fractal, due to the
      slow, purely quantum algebraic decay in time produced by dynamical localization.
      Such findings considerably enlarge the scope of the existing theory.

PMID- 11461468
TI  - Dynamic long-term anticipation of chaotic states.
AB  - Introducing a short time delay into the coupling of two synchronizing chaotic
      systems, it was shown recently that the driven system may anticipate the driving
      system in real time. Augmenting the phase space of the driven system, we
      accomplish anticipation times that are multiples of the coupling delay time and
      exceed characteristic time scales of the chaotic dynamics. The stability
      properties of the associated anticipatory synchronization manifold in certain
      cases turn out to be the same as for identically synchronizing oscillators.

PMID- 11461469
TI  - Zonal flow and zonal magnetic field generation by finite beta drift waves: a
      theory for low to high transitions in tokamaks.
AB  - The understanding of low to high (L-H) transition in tokamaks has been an
      important area of investigation for more than a decade. Recent 3D finite beta
      simulations of drift-resistive ballooning modes in a flux tube geometry by Rogers
      et al. [Phys. Rev. Lett. 81, 4396 (1998)] have provided a unique parametrization
      of the transition in a two-dimensional phase space. Comparison of the threshold
      curve in this phase space with data from ASDEX and C-MOD has shown very good
      agreement. In this Letter we provide a simple theory, based on the generation of
      zonal flow and zonal magnetic field in a finite-beta plasma, which explains this
      threshold curve for L-H transition in tokamaks.

PMID- 11461470
TI  - Plasma dynamics in capillary discharge soft x-ray lasers.
AB  - The dynamics and stability of collapsing gas columns, generated by a fast
      capillary discharge setup, are studied for obtaining soft x-ray amplification in
      highly ionized ions. Electron temperature and density measurements at the peak of
      the compression stage are used for tuning the discharge parameters. Once the
      needed conditions were achieved, strong amplification of the 3s-3p transition in
      Ne-like Ar ions at 469 A is observed. A gain coefficient of >0.75 cm(-1) and a
      beam divergence of <5 mrad are measured along plasma columns of <150 microm
      diameter and up to 165 mm length.

PMID- 11461471
TI  - Theory for the ultrafast ablation of graphite films.
AB  - The physical mechanisms for damage formation in graphite films induced by
      femtosecond laser pulses are analyzed using a microscopic electronic theory. We
      describe the nonequilibrium dynamics of electrons and lattice by performing
      molecular dynamics simulations on time-dependent potential energy surfaces. We
      show that graphite has the unique property of exhibiting two distinct laser
      induced structural instabilities. For high absorbed energies ( >3.3 eV/atom) we
      find nonequilibrium melting followed by fast evaporation. For low intensities
      above the damage threshold ( >2.0 eV/atom) ablation occurs via removal of intact
      graphite sheets.

PMID- 11461472
TI  - A new opto-mechanical effect in solids.
AB  - We propose that large, reversible shape changes in solids, of between 10%-400%,
      can be induced optically by photoisomerizing monodomain nematic elastomers.
      Empirical and molecular analysis of shape change and its relation to thermal
      effects is given along with a simple model of the dynamics of response. Our
      experiments demonstrate these effects for the first time and theory is compared
      qualitatively with our results.

PMID- 11461473
TI  - Structural evidence for Ta-tetramerization displacements in the charge-density
      wave compound (TaSe4)2I from x-ray anomalous diffraction.
AB  - We use the anomalous x-ray diffraction technique to investigate the nature of the
      tantalum displacement pattern in the modulated phase of the charge-density-wave
      compound (TaSe4)2I. In addition to the known acousticlike modulation, we find the
      first direct evidence for the condensation of opticlike Ta displacements along
      the metallic chains corresponding to an LLSS pattern of long and short in-chain
      Ta-Ta distances (Ta-tetramerization modes). This result confirms a previous model
      in which the interaction of the electronically coupled optic modes with long
      wavelength acoustic shear modes leads to the condensation of a modulation of
      mixed character.

PMID- 11461474
TI  - Combinatorial study of surface pattern formation in thin block copolymer films.
AB  - Surface pattern formation in diblock copolymer films is investigated as a
      function of film thickness h and molecular mass M. Smooth films are observed for
      certain h ranges centered about multiples of the lamellar thickness L0, and we
      attribute this effect to an increase in the surface chain density with h in the
      outer brushlike copolymer layer. We also observe apparently stable labyrinthine
      surface patterns for other h ranges, and the average size of these patterns is
      found to scale as lambda approximately L0(-2.5). Hole and island patterns occur
      for h ranges between those of the labyrinthine patterns and the smooth regions,
      and their size similarly decreases with L0 and M.

PMID- 11461475
TI  - Electronic energy relaxation and transition frequency jumps of single molecules
      at 30 mK.
AB  - Transition frequency jumps for single terrylene molecules in a polyethylene
      matrix caused by resonant laser irradiation are investigated at 30 mK. These
      jumps are not accompanied by substantial sample heating. A model for the effect
      is proposed, based on the interaction of tunneling two-level systems (TLSs)
      surrounding the single molecule with high-energy nonthermal phonons emitted by
      the molecule during electronic energy relaxation. The radius of the effective
      interaction volume is estimated to be r(m) approximately 12.5 nm, and the
      interaction cross section for nonequilibrium phonon-TLS scattering is estimated
      as approximately 10(-22) cm2.

PMID- 11461476
TI  - Probable Langevin-like director reorientation in an interface-induced disordered
      SmC*-like state of liquid crystals characterized by frustration between ferro-
      and antiferroelectricity.
AB  - To clarify the thresholdless, hysteresis free V-shaped switching due to
      frustration between ferro- and antiferroelectricity, we have studied a prototype
      binary mixture system. The apparent orientational order parameters, <P2> and
      <P4>, obtained from polarized Raman scattering in thin homogeneous cells indicate
      that substrate interfaces induce some randomization of local in-plane directors
      at the tip of the V. Their correlation lengths, xi( parallel) approximately 3.5
      nm and xi( perpendicular) approximately 75 nm, have been estimated by assuming
      the Langevin-like reorientation. Because of the much shorter xi(parallel) and
      xi(perpendicular) than the visible light wavelength, the switching process looks
      uniform.

PMID- 11461477
TI  - Ultra-high-resolution electron microscopy of carbon nanotube walls.
AB  - The resolution in scanning transmission electron microscopy may be enhanced by
      taking advantage of the information contained in the nanodiffraction patterns
      recorded for each position of the scanning incident beam. We have demonstrated
      the first production of ultrahigh resolution, better than 0.1 nm, by this method,
      in the imaging of an essentially one-dimensional object, the wall of a
      multiwalled carbon nanotube, using an instrument for which the resolution for
      normal imaging is about 0.3 nm.

PMID- 11461478
TI  - Superconformal electrodeposition in submicron features.
AB  - Superconformal electrodeposition is explained based on a local growth velocity
      that increases with coverage of a catalytic species adsorbed on the copper
      electrolyte interface. For dilute concentration of the catalyst precursor in the
      electrolyte, local coverage in fine features changes more due to interface area
      change than by accumulation from the electrolyte, yielding superconformal growth.
      The model is supported by experiments and simulations of copper deposition in 350
      100 nm wide features, helping to explain the influence of adsorbates on roughness
      evolution.

PMID- 11461479
TI  - Origin of the different reconstructions of diamond, Si, and Ge(111) surfaces.
AB  - Ab initio calculations of the 2x1, c(2x8), and 7x7 reconstructions of the
      diamond, Si, and Ge(111) surfaces are reported. The pi-bonded chain, adatom, and
      dimer-adatom-stacking fault models are studied to understand the driving forces
      for a certain reconstruction. The resulting energetics, geometries, and band
      structures are compared for the elemental semiconductors with different atomic
      sizes, and chemical trends are derived. We show why the lowest-energy
      reconstructions are different for the group-IV materials considered.

PMID- 11461480
TI  - Dewetting: film rupture by nucleation in the spinodal regime.
AB  - Unstable thin liquid films on solid substrates dewet by hole nucleation on
      defects or by a linear surface instability (spinodal dewetting). A system with
      destabilizing short-range and stabilizing long-range molecular interactions is
      investigated. We show that, for a subrange within the linearly unstable film
      thickness range, nucleation determines the final structure, whereas spinodal
      dewetting is of negligible influence. The results are also applicable to the
      spinodal decomposition of binary mixtures.

PMID- 11461481
TI  - Role of electronic correlation in the Si(100) reconstruction: a quantum Monte
      Carlo study.
AB  - Recent low-temperature scanning tunneling experiments have questioned the
      generally accepted picture of buckled silicon dimers as the ground state
      reconstruction of the Si(100) surface, undermining the ability of density
      functional theory to accurately describe electronic correlations at surfaces. We
      present quantum Monte Carlo calculations on large cluster models of the surface,
      and conclude that buckling remains energetically favorable even when the present
      day best treatment of electronic correlation is employed. The implications for
      experimental interpretation are discussed.

PMID- 11461482
TI  - CaB6: a new semiconducting material for spin electronics.
AB  - Ferromagnetism was recently observed at unexpectedly high temperatures in La
      doped CaB6. The starting point of all theoretical proposals to explain this
      observation is a semimetallic electronic structure calculated for CaB6 within the
      local density approximation. Here we report the results of parameter-free
      quasiparticle calculations of the single-particle excitation spectrum which show
      that CaB6 is not a semimetal but a semiconductor with a band gap of 0.8+/-0.1 eV.
      Magnetism in La(x)Ca1-xB6 occurs just on the metallic side of a Mott transition
      in the La-induced impurity band.

PMID- 11461483
TI  - Room-temperature spin injection from Fe into GaAs.
AB  - Injection of spin polarized electrons from a metal into a semiconductor is
      demonstrated for a GaAs/(In,Ga)As light emitting diode covered with Fe. The
      circular polarization degree of the observed electroluminescence reveals a spin
      injection efficiency of 2%. The underlying injection mechanism is explained in
      terms of a tunneling process.

PMID- 11461484
TI  - Kondo resonance in a mesoscopic ring coupled to a quantum dot: exact results for
      the Aharonov-Bohm-Casher effects.
AB  - We study the persistent currents induced by both the Aharonov-Bohm and Aharonov
      Casher effects in a one-dimensional mesoscopic ring coupled to a sidebranch
      quantum dot at Kondo resonance. For privileged values of the Aharonov-Bohm-Casher
      fluxes, the problem can be mapped onto an integrable model, exactly solvable by a
      Bethe ansatz. In the case of a pure magnetic Aharonov-Bohm flux, we find that the
      presence of the quantum dot has no effect on the persistent current. In contrast,
      the Kondo resonance interferes with the spin-dependent Aharonov-Casher effect to
      induce a current which, in the strong-coupling limit, is independent of the
      number of electrons in the ring.

PMID- 11461485
TI  - Mobility of the doped holes and the antiferromagnetic correlations in underdoped
      high- Tc cuprates.
AB  - The emergence and the evolution of the metallic charge transport in the La2
      xSrxCuO4 system from lightly to optimally doped samples (x = 0.01-0.17) are
      studied. We demonstrate that in high-quality single crystals the in-plane
      resistivity shows a metallic behavior for all values of x at moderate
      temperatures and that the hole mobility at 300 K changes only by a factor of 3
      from x = 0.01 to 0.17, where its x dependence is found to be intriguingly similar
      to that of the inverse antiferromagnetic correlation length. We discuss an
      incoherent-metal picture and a charged-stripe scenario as candidates to account
      for these peculiar features.

PMID- 11461486
TI  - Effects of dissipation on a superconducting single electron transistor.
AB  - We measure the effect of dissipation on the minimum zero-bias conductance,
      G(min)0, of a superconducting single electron transistor (sSET) capacitively
      coupled to a two-dimensional electron gas (2DEG) in a GaAs/AlGaAs
      heterostructure. Depleting the 2DEG with a back gate voltage decreases the
      dissipation experienced by the sSET in situ. We find that G(min)0 increases as
      the dissipation is increased or the temperature is reduced; the functional forms
      of these dependences are compared with the model of Wilhelm et al. in which the
      leads coupled to the sSET are represented by lossy transmission lines.

PMID- 11461487
TI  - Superconducting vortices in ac fields: does the Kohn theorem work?
AB  - Electrodynamics of clean pinning-free type II superconductors in the mixed state
      is derived using the Boltzmann kinetic equations for excitations. The condition
      of the vortex cyclotron resonance is found. The reason why this resonance does
      not comply with the Kohn theorem is discussed.

PMID- 11461488
TI  - Nonequilibrium transitions in fully frustrated Josephson junction arrays.
AB  - We study the effect of thermal fluctuations in a fully frustrated Josephson
      junction array driven by a current I larger than the apparent critical current
      I(c)(T). We calculate numerically the behavior of the chiral order parameter of
      Z2 symmetry and the transverse helicity modulus [related to the U(1) symmetry] as
      a function of temperature. We find that the Z2 transition occurs at a temperature
      T(Z2)(I) which is lower than the temperature T(U(1))(I) for the U(1) transition.
      Both transitions could be observed experimentally from measurements of the
      longitudinal and transverse voltages.

PMID- 11461489
TI  - Phonon density of states in MgB2.
AB  - We report inelastic neutron scattering measurements of the phonon density of
      states in Mg 11B2, which has a superconducting transition at 39.2 K. The acoustic
      phonons extend in energy to 36 meV, and there are highly dispersive optic
      branches peaking at 54, 78, 89, and 97 meV. A simple Born-von Karman model
      reproduces the mode energies, and provides an estimate of the electron-phonon
      coupling of lambda approximately 0.9. Furthermore, the estimated boron and
      magnesium contributions to the isotope effect are in qualitative agreement with
      experiment. The data confirm that a conventional phonon mechanism, with
      moderately strong electron-phonon coupling, can explain the observed
      superconductivity.

PMID- 11461490
TI  - History effects and phase diagram near the lower critical point in YBa2Cu3O7
      single crystals.
AB  - Using a sensitive torque magnetometer we have studied magnetization curves for
      untwinned overdoped YBa2Cu3O7 single crystals in fields of up to 28 T. We
      demonstrate the existence of history effects below the lower critical point and
      provide a full demarcation of the Bragg-glass phase. A pronounced symmetry is
      observed in the behavior of the phase lines, irreversible magnetization, and
      value of the magnetization jump near both critical points.

PMID- 11461491
TI  - Unusual magnetic susceptibility anisotropy in untwinned La2-xSr(x)CuO4 single
      crystals in the lightly doped region.
AB  - We present a study of the magnetic susceptibility chi in carefully detwinned La 2
      xSr(x)CuO4 single crystals in the lightly doped region (x = 0-0.03), which
      demonstrates a remarkable in-plane anisotropy of the spin system. This
      anisotropy, chi(a)/chi(b), is found to persist after the long-range
      antiferromagnetic (AF) order is destroyed by hole doping, suggesting that doped
      holes break the AF order into domains in which the spin alignment is kept
      essentially intact. It turns out that the freezing of the spins taking place at
      low temperatures is also notably anisotropic, implying that the "spin-glass"
      feature is governed by the domain structure as well.

PMID- 11461492
TI  - Multiparticle states in the S = 1 chain system CsNiCl3.
AB  - A continuum of magnetic states has been observed by neutron scattering from the
      spin-1 chain compound CsNiCl3 in its disordered gapped one-dimensional phase.
      Results using both triple-axis and time-of-flight spectrometers show that around
      the antiferromagnetic point Qc = pi, the continuum lies higher in energy than the
      Haldane gapped excitations. At 6 K the integrated intensity of the continuum is
      about 12(2)% of the total spectral weight. This result is considerably larger
      than the 1%-3% weight predicted by the nonlinear sigma model for the three
      particle continuum.

PMID- 11461493
TI  - Continuum in the spin-excitation spectrum of a haldane chain observed by neutron
      scattering in CsNiCl3.
AB  - The spin-excitation continuum, expected to dominate the low-energy fluctuation
      spectrum in the Haldane spin chain around the Brillouin zone center, q = 0, is
      directly observed by inelastic magnetic neutron scattering in the S = 1 quasi-1D
      antiferromagnet CsNiCl3. We find that the single mode approximation fails, and
      that a finite energy width appears in the dynamic correlation function S(q,omega)
      for q less, similar 0.5 pi. The width increases with decreasing q, while
      S(q,omega) acquires an asymmetric shape qualitatively similar to that predicted
      for the two-magnon continuum in the nonlinear sigma-model.

PMID- 11461494
TI  - Ultrafast conductivity dynamics in colossal magnetoresistance manganites.
AB  - Ultrafast picosecond measurements of optically induced changes in the absolute
      conductivity (0.4-1.0 THz) of La0.7M0.3MnO3 thin films ( M = Ca, Sr) from 10 K to
      approximately 0.9 Tc reveal a two-component relaxation. A fast, approximately 2
      ps, conductivity decrease arises from an optically induced modification of the
      effective phonon temperature. The slower component, related to spin-lattice
      relaxation, has a lifetime that increases upon approaching Tc from below in
      accordance with an increasing spin specific heat. We show that, for T<<Tc,
      partial differential sigma/ partial differential T is primarily determined by
      thermally disordered phonons while spin fluctuations dominate near Tc.

PMID- 11461495
TI  - Interpretation of resonant photoemission spectra of solid actinide systems.
AB  - It is shown that valence-band photoemission (PE) spectra of epitaxial hcp films
      of U metal may be understood within a one-step model of PE based on an itinerant
      description of the U 5f states. Particularly, the PE intensities of the f-derived
      bands are correctly reproduced for photon energies between 60 and 103 eV. It is
      found that a cross-section minimum of the Fermi-energy feature at h(nu) = 90-94
      eV, which previously was assigned to a Fano antiresonance at the 5d-->5f
      excitation threshold, is mainly caused by a Cooper minimum. Analogous 5f cross
      section variations in the region of the 5d-->5f resonances were obtained for UPd3
      and Pu metal.

PMID- 11461496
TI  - Natural thermal and magnetic entanglement in the 1D Heisenberg model.
AB  - We investigate the entanglement between any two spins in a one dimensional
      Heisenberg chain as a function of temperature and the external magnetic field. We
      find that the entanglement in an antiferromagnetic chain can be increased by
      increasing the temperature or the external field. Increasing the field can also
      create entanglement between otherwise disentangled spins. This entanglement can
      be confirmed by testing Bell's inequalities involving any two spins in the solid.

PMID- 11461497
TI  - Compressibility of quantum mixed-state signals.
AB  - We present a formula that determines the optimal number of qubits per message
      that allows asymptotically faithful compression of the quantum information
      carried by an ensemble of mixed states. The set of mixed states determines a
      decomposition of the Hilbert space into the redundant part and the irreducible
      part. After removing the redundancy, the optimal compression rate is shown to be
      given by the von Neumann entropy of the reduced ensemble.

PMID- 11461498
TI  - Comment about pion electro-production and the axial form factors.

PMID- 11461500
TI  - Comment on: "intrinsic ferroelectric coercive field".

PMID- 11461542
TI  - Optics with an atom laser beam.
AB  - We report on the atom optical manipulation of an atom laser beam. Reflection,
      focusing, and its storage in a resonator are demonstrated. Precise and versatile
      mechanical control over an atom laser beam propagating in an inhomogeneous
      magnetic field is achieved by optically inducing spin flips between atomic ground
      states with different magnetic moment. The magnetic force acting on the atoms can
      thereby be effectively switched on and off. The surface of the atom optical
      element is determined by the resonance condition for the spin flip in the
      inhomogeneous magnetic field. More than 98% of the incident atom laser beam is
      reflected specularly.

PMID- 11461543
TI  - Chern-Simons theories on the noncommutative plane.
AB  - We investigate U(N) Chern-Simons theories on the noncommutative plane. We show
      that for the theories to be consistent quantum mechanically, the coefficient of
      the Chern-Simons term should be quantized kappa = n/2pi with an integer n. This
      is a surprise for the U(1) gauge theory. When uniform background charge density
      rho(e) is present, the quantization rule changes to kappa+rho(e)straight theta =
      n/2pi with the noncommutative parameter straight theta. With the exact expression
      for the angular momentum, we argue in the U(1) theory that charged particles in
      the symmetric phase carry fractional spin 1/2n and vortices in the broken phase
      carry half-integer or integer spin -n/2.

PMID- 11461544
TI  - Level quantization for the noncommutative Chern-Simons theory.
AB  - We show that the coefficient of the three-dimensional Chern-Simons action on the
      noncommutative plane must be quantized. Similar considerations apply in other
      dimensions as well.

PMID- 11461545
TI  - Fragmented condensate ground state of trapped weakly interacting bosons in two
      dimensions.
AB  - The ground state and its structure for a rotating, harmonically trapped N-boson
      system with a weak repulsive contact interaction are studied as the angular
      momentum L increases up to 3N. We show that the ground state is generally a
      fragmented condensate due to angular momentum conservation. In response to an
      (arbitrarily weak) asymmetric perturbation of the trap, however, the fragmented
      ground state can be transformed into a single condensate state. We manifest this
      intrinsic instability by calculating the conditional probability distributions,
      which show patterns analogous to the boson density distributions predicted by
      mean-field theory.

PMID- 11461546
TI  - Inequivalence of ensembles in a system with long-range interactions.
AB  - We study the global phase diagram of the infinite-range Blume-Emery-Griffiths
      model both in the canonical and in the microcanonical ensembles. The canonical
      phase diagram shows first-order and continuous transition lines separated by a
      tricritical point. We find that below the tricritical point, when the canonical
      transition is first order, the phase diagrams of the two ensembles disagree. In
      this region the microcanonical ensemble exhibits energy ranges with negative
      specific heat and temperature jumps at transition energies. These results can be
      extended to weakly decaying nonintegrable interactions.

PMID- 11461547
TI  - Wideband dual sphere detector of gravitational waves.
AB  - We present the concept of a sensitive and broadband resonant mass gravitational
      wave detector. A massive sphere is suspended inside a second hollow one. Short,
      high-finesse Fabry-Perot optical cavities read out the differential displacements
      of the two spheres as their quadrupole modes are excited. At cryogenic
      temperatures, one approaches the standard quantum limit for broadband operation
      with reasonable choices for the cavity finesses and the intracavity light power.
      A molybdenum detector, of overall size of 2 m, would reach spectral strain
      sensitivities of 2x10(-23) Hz(-1/2) between 1000 and 3000 Hz.

PMID- 11461548
TI  - Probing large distance higher-dimensional gravity with cosmic microwave
      background measurements.
AB  - Higher-dimensional gravity theories may manifest themselves not only at short
      microscopic distances but also at large cosmological scales. We study the
      constraints that cosmic microwave background measurements set on such large
      distance modifications of the gravitational potential.

PMID- 11461549
TI  - Superfluid phase transitions in dense neutron matter.
AB  - The phase transitions in a realistic system with triplet pairing, dense neutron
      matter, have been investigated. The spectrum of phases of the 3P2-3F2 model,
      which adequately describes pairing in this system, is analytically constructed
      with the aid of a separation method for solving BCS gap equations in states of
      arbitrary angular momentum. In addition to solutions involving a single value of
      the magnetic quantum number (and its negative), there exist ten real
      multicomponent solutions. Five of the corresponding angle-dependent order
      parameters have nodes, and five do not. In contrast to the case of superfluid
      3He, transitions occur between phases with nodeless order parameters.

PMID- 11461550
TI  - Gauge invariances and phases of massive higher spins in (anti-) de Sitter space.
AB  - The (m2,Lambda) plane of spin s>1 massive fields in (anti-) de Sitter space
      backgrounds is shown to consist of separate phases, divided by lines of novel
      "partially massless" gauge theories that successively remove helicities, starting
      from the lowest, 0 or +/-1/2. The norms of the excluded states flip as the gauge
      lines are crossed and only the region containing the massive Minkowski theory is
      unitary. The partially massless gauge theories are unitary or not, depending on
      the ordering of the gauge lines. This "level splitting" of massless Minkowski
      gauge theories is specific to nonzero Lambda.

PMID- 11461551
TI  - Number of fermion generations derived from anomaly cancellation.
AB  - We prove that global anomaly cancellation requires more than one generation of
      quarks and leptons, provided that the standard model fields propagate in two
      universal extra dimensions. Furthermore, if the fermions of different generations
      have the same gauge charges and chiralities, then global anomaly cancellation
      implies that there must be three generations.

PMID- 11461552
TI  - Observation of coherent transients in ultrashort chirped excitation of an
      undamped two-level system.
AB  - The effects of coherent excitation of a two-level system with a linearly chirped
      pulse are studied theoretically and experimentally [in Rb (5s-5p)] in the low
      field regime. The coherent transients are measured directly on the excited state
      population on an ultrashort time scale. A sharp step corresponds to the passage
      through resonance. It is followed by oscillations resulting from interferences
      between off-resonant and resonant contributions. We finally show the equivalence
      between this experiment and Fresnel diffraction by a sharp edge.

PMID- 11461553
TI  - Selectivity in the excitation of fermi-coupled vibrations in CO2 by impact of
      slow electrons.
AB  - Improvement of resolution of a gas phase hemispherical electron spectrometer (to
      7 meV FWHM) permitted separate measurements of the excitation of each member of
      the well known Fermi dyad in CO2 by impact of slow electrons. Absolute
      differential cross sections at a scattering angle of 135 degrees were measured as
      a function of electron energy. The excitation was found to be highly selective
      both via the 2Pi(u) shape resonance around 3.6 eV and via the virtual CO2- state
      at low energy. The selectivity is surprising because both vibrational states
      ensuing from the Fermi resonance involve the same type of nuclear motion (bending
      and stretch) and excitation of both is symmetry allowed.

PMID- 11461554
TI  - Superelastic scattering of electrons from highly charged ions with inner shell
      vacancies.
AB  - We report the measurement of electrons scattered superelastically from highly
      charged ions having an initial K-shell vacancy. In this process, the scattered
      electron gains approximately 725 eV of energy from the deexcitation of an excited
      He-like F7+(1s2s 3S) metastable ion to its ground state. Theoretical calculations
      based on an R-matrix approach agree well in position, shape, and magnitude with
      the experimental data.

PMID- 11461555
TI  - Nuclear fusion induced by Coulomb explosion of heteronuclear clusters.
AB  - We propose a new mechanism for the production of high-energy ( E>3 keV)
      deuterons, suitable to induce dd nuclear fusion, based on multielectron
      ionization and Coulomb explosion of heteronuclear deuterium containing molecular
      clusters, e.g., (D2O)n, in intense ( 10(16)-2x10(18) W/cm2) laser fields. Cluster
      size equations for E, in conjunction with molecular dynamics simulations, reveal
      important advantages of Coulomb explosion of (D2O)n heteronuclear clusters, as
      compared with (D)n clusters. These involve the considerably increased D+ kinetic
      energy and a narrow, high-energy distribution of deuterons.

PMID- 11461556
TI  - Femtosecond light source for phase-controlled multiphoton ionization.
AB  - We describe a femtosecond Raman light source with more than an octave of optical
      bandwidth. We use this source to demonstrate phase control of multiphoton
      ionization under conditions where ionization requires eleven photons of the
      lowest frequency of the spectrum or five photons of the highest frequency. The
      nonlinearity of the photoionization process allows us to characterize the light
      source. Experiment-to-theory comparison implies generation of a near single-cycle
      waveform.

PMID- 11461557
TI  - Necklace-ring vector solitons.
AB  - We introduce novel classes of optical vector solitons that consist of
      incoherently coupled self-trapped "necklace" beams carrying zero, integer, and
      even fractional angular momentum. Because of the stabilizing mutual attraction
      between the components, such stationary localized structures exhibit quasistable
      propagation for much larger distances than the corresponding scalar vortex
      solitons and expanding scalar necklace beams.

PMID- 11461558
TI  - Experimental demonstration of the Fermi-Pasta-Ulam recurrence in a modulationally
      unstable optical wave.
AB  - Through a detailed spectral analysis of the propagation of square-shaped laser
      pulses in optical fibers, we provide the experimental demonstration of the Fermi
      Pasta-Ulam recurrence phenomenon in modulationally unstable optical waves ruled
      by the nonlinear Schrodinger equation.

PMID- 11461559
TI  - Dynamical turbulent flow on the Galton board with friction.
AB  - We study numerically and analytically the dynamics of charged particles on the
      Galton board, a regular lattice of disk scatters, in the presence of constant
      external force, magnetic field, and friction. It is shown that under certain
      conditions friction leads to the appearance of a strange chaotic attractor. In
      this regime the average velocity and direction of particle flow can be
      effectively affected by electric and magnetic fields. We discuss the applications
      of these results to the charge transport in antidot superlattices and the stream
      of suspended particles in a viscous flow through scatters.

PMID- 11461560
TI  - Electro-optic measurement of the wake fields of a relativistic electron beam.
AB  - When a relativistic electron bunch traverses a structure, strong electromagnetic
      fields are induced in its wake. For a 12 nC bunch of duration 4.2 ps FWHM, the
      peak field is measured >0.5 MV/m. Time resolution of approximately 5 ps is
      achieved using electro-optic sampling with a lithium tantalate (LiTaO3) crystal
      and a short-pulse infrared laser synchronized to the beam. We present
      measurements for both the longitudinal and radial components of the field and
      relate them to the wall impedance.

PMID- 11461561
TI  - Resonant emittance transfer driven by space charge.
AB  - Space charge can lead to emittance and/or energy exchange known as
      "equipartitioning issue" in linacs, or space-charge coupling in high-current
      synchrotrons. It is described here as an internal resonance driven by the self
      consistent space-charge potential of coherent eigenmodes. By a detailed
      comparison of analytical theory with 2D particle-in-cell simulation for
      Kapchinskij-Vladimirskij (KV) and waterbag distributions, we discuss
      characteristic features of this resonance mechanism in the vicinity of the
      symmetric focusing resonance band--for practical purposes, the most important
      case--and discuss the applicability of the linearized KV theory.

PMID- 11461562
TI  - Loss of second-ballooning stability in three-dimensional equilibria.
AB  - The effect of three-dimensional geometry on the stability boundaries of ideal
      ballooning modes is investigated. In particular, the relationship between the
      symmetry properties of the local shear and the magnetic curvature is addressed
      for quasisymmetric configurations. The presence of symmetry breaking terms in the
      local shear can produce localized ballooning instabilities in regions of small
      average magnetic shear which lower first-ballooning stability thresholds and can
      potentially eliminate the second stability regime.

PMID- 11461563
TI  - Observation of the superfluid shapiro effect in a 3He weak link.
AB  - We have studied the mass currents through a superfluid 3He Josephson weak link in
      the presence of an externally applied ac pressure modulation. Characteristic
      changes in the dc mass currents are observed whenever the superfluid Josephson
      frequency omega(J) is an integer multiple of the ac modulation frequency omega.
      The measured dependencies of these current changes on ac pressure amplitude are
      in excellent agreement with theory describing quantum phase dynamics of
      superfluid 3He weak links. These results establish the superfluid analog of the
      superconducting Shapiro effect.

PMID- 11461564
TI  - Is there something of mode coupling theory in orientationally disordered
      crystals?
AB  - Molecular dynamics simulations have been performed on the orientationally
      disordered crystal chloroadamantane. We stress that universal behavior,
      relatively well described by the mode coupling theory, is shared by systems whose
      dynamics are almost completely controlled by translations or rotations. This
      investigation also shows the existence of a second remarkable dynamical crossover
      at the temperature Tx>Tc, consistent with a previous NMR and molecular dynamics
      study [F. Affouard et al., Europhys. Lett. 53, 611 (2001)]. This allows us to
      support clearly the existence of a "landscape-influenced" regime as recently
      proposed [S. Sastry et al., Nature 393, 554 (1998)].

PMID- 11461565
TI  - Breather induced modification of the speed of sound.
AB  - The modification of the speed of sound induced by the presence of breathers in a
      quasi-one-dimensional magnetic chain is examined in the framework of the sine
      Gordon model. Within the "pseudoharmonic" phonon approximation it was found that
      the spin-phonon interaction could have a significant influence on the phonon
      frequencies, and it consequently leads to the modification of the speed of sound
      which, in the case of breathers, shows quite different magnetic field and
      temperature behavior when compared to the case of the linear excitations and
      solitons. An interesting possibility of an indirect experimental examination of
      the breathers arises from these predictions.

PMID- 11461566
TI  - Theoretical identification of the smallest fullerene, C20.
AB  - By using first-principles calculations, we calculate the vibronic fine structure
      in photoelectron spectra of C-20 clusters. Based on our results, we assign one of
      the recently observed spectra [H. Prinzbach et al., Nature (London) 407, 60
      (2000)] to the fullerene structure and, therefore, confirm the experimental claim
      that the smallest fullerene is really synthesized.

PMID- 11461567
TI  - Orthorhombic intermediate state in the zinc blende to rocksalt transformation
      path of SiC at high pressure.
AB  - The mechanism of the B3/B1 phase transition of SiC has been investigated by
      periodic LCAO-DFT least-enthalpy calculations. A new transformation pathway,
      based on a Pmm2 orthorhombic intermediate state with two SiC units per cell, is
      found to be energetically favored over the traditional R3m mechanism. The
      computed activation enthalpy is 0.75 eV/SiC unit at the predicted transition
      pressure of 92 GPa (B3LYP functional). Activation enthalpy and activation volume
      vs pressure are analyzed to characterize the kinetic aspects of the
      transformation.

PMID- 11461568
TI  - Surface reconstruction of an ordered fluid: an analogy with crystal surfaces.
AB  - The surface structure of a lamellar polystyrene-block-polybutadiene-block
      polymethylmethacrylate (SBM) triblock copolymer forms a complex reconstruction,
      which breaks the two-dimensional continuous translational symmetry of an ideal
      (homogeneous) SBM surface. Despite the very different types of matter and order,
      our findings reveal a remarkable analogy with the well-known phenomenon of
      surface reconstruction of single crystals, in particular, with the (2x1)
      "buckling row" reconstruction of the Si(100) surface. Similarities and
      differences between both classes of materials are discussed on the basis of
      symmetry considerations.

PMID- 11461569
TI  - Footprints in sand: the response of a granular material to local perturbations.
AB  - We experimentally determine ensemble-averaged responses of granular packings to
      point forces, and we compare these results to recent models for force propagation
      in a granular material. We use 2D granular arrays consisting of photoelastic
      particles: either disks or pentagons, thus spanning the range from ordered to
      disordered packings. A key finding is that spatial ordering of the particles is a
      key factor in the force response. Ordered packings have a propagative component
      that does not occur in disordered packings.

PMID- 11461570
TI  - Modification of the superfluid 3He phase diagram by impurity scattering.
AB  - The effect of impurity scattering on the phase diagram of pure superfluid 3He has
      been investigated by acoustic techniques near the bulk polycritical pressure.
      Impurities were introduced with a 98% porous silica aerogel. In zero applied
      field, the equilibrium phase is a B phase, consistent with predictions from
      isotropic scattering. The superfluid transition in a magnetic field at 25 bars is
      from normal to A phase and is independent of the magnetic field up to 2.9 kG. A
      first-order phase transition between A and B superfluids is observed with
      surprisingly strong supercooling in both zero and nonzero applied field.

PMID- 11461571
TI  - Alloying effects on electromigration mass transport.
AB  - Small amounts of alloying elements can significantly retard electromigration in
      conductor lines. This phenomenon is experimentally well established but is still
      lacking a fundamental explanation. An atomic-level mechanism for this behavior is
      proposed here which is based on a kinetic analysis of diffusion in crystalline
      interfaces. It predicts a reduction or reversal of the flux of host atoms for
      physically reasonable parameters and can account for the observed effect of
      copper on electromigration in aluminum conductor lines.

PMID- 11461572
TI  - Surface Patterson function by inversion of low-energy electron diffraction I-V
      spectra at multiple incident angles.
AB  - An accurate Patterson function, free of artifacts, is obtained by transforming
      low-energy electron diffraction I-V spectra at multiple incident angles. The
      demonstration is carried out using normal incidence measured spectra and
      calculated spectra at three angles of incidence. The errors between intensity
      spots in the Patterson function and known interatomic distances are less than
      0.01 A in the horizontal direction and 0.09 A in the vertical direction. The
      reason for the high accuracy in the horizontal direction is given.

PMID- 11461573
TI  - Corners, cusps, and pearls in running drops.
AB  - Small drops sliding down a partially wetting substrate bifurcate between
      different shapes depending on their capillary number Ca. At low Ca, they are
      delimited by a rounded, smooth contact line. At intermediate values they develop
      a corner at the trailing edge, the angle of which evolves from flat to 60 degrees
      with increasing velocity. Further up, they exhibit a cusped tail that emits
      smaller drops ("pearls"). These bifurcations may be qualitatively and
      quantitatively recovered by considering the dynamic contact angle along the
      contact line.

PMID- 11461574
TI  - Adsorption sites and ligand effect for CO on an alloy surface: a direct view.
AB  - CO adsorption on a PtCo(111) surface was studied by scanning tunneling
      microscopy. Comparison of images with chemical contrast of Pt and Co and images
      showing the CO molecules indicates that CO resides exclusively on top of Pt sites
      and never on Co. CO bonding is highly sensitive to the chemical environment. The
      probability to find CO on a Pt atom increases drastically with the number of its
      Co nearest neighbors. Ab initio calculations show that this ligand effect is due
      to different positions of the center of the Pt d band.

PMID- 11461575
TI  - Two-atom structures of Ge on Si(100): dimers versus adatom pairs.
AB  - We present an ab initio study of the properties of structures composed of two and
      four Ge atoms adsorbed on the troughs of the Si(100) surface, and we conclude
      that these structures are all composed of dimers, with a chemical bonding between
      the adatoms. We compare our calculated local density of states with scanning
      tunneling microscope (STM) images, and we show that these Ge dimers adsorbed on
      the troughs between the substrate dimer rows can be identified with the adatom
      pairs observed experimentally. We also show that the local buckling of the
      substrate dimers can give rise to similar structures with very different STM
      images.

PMID- 11461576
TI  - Model for intrinsic stress formation in amorphous thin films.
AB  - Metallic amorphous thin films evaporated on a substrate can be characterized by
      different growth regimes in dependence of the film thickness concerning surface
      morphology and intrinsic film stresses, independent of the details of the applied
      material systems. Here, a model is presented to link the surface topography and
      characteristic surface measures with the observed film stresses. This allows
      quantitative prediction of stresses in dependence of film preparation parameters
      for a tailored film production.

PMID- 11461577
TI  - Quantum Monte Carlo analysis of exchange and correlation in the strongly
      inhomogeneous electron gas.
AB  - We use the variational quantum Monte Carlo method to calculate the density
      functional exchange-correlation hole n(xc), the exchange-correlation energy
      density e(xc), and the total exchange-correlation energy E(xc) of several
      strongly inhomogeneous electron gas systems. We compare our results with the
      local density approximation and the generalized gradient approximation. It is
      found that the nonlocal contributions to e(xc) contain an energetically
      significant component, the magnitude, shape, and sign of which are controlled by
      the Laplacian of the electron density.

PMID- 11461578
TI  - Hard correlation gap observed in quench-condensed ultrathin beryllium.
AB  - We report on the tunneling density of states (DOS) in strongly disordered
      ultrathin Be films quench condensed at 20 K. Above 5 K, the DOS shows the well
      known logarithmic anomaly at the Fermi level. Only in a narrow temperature range
      near 2 K is the DOS linearly dependent on energy, as predicted by Efros and
      Shklovskii. However, both the zero-bias conductance and the slope of the linear
      DOS are found to decrease drastically with decreasing temperature. Tunneling
      measurements at mK temperatures have revealed conclusively that a hard
      correlation gap opens up in the DOS.

PMID- 11461579
TI  - Evolution of fractal patterns during a classical-quantum transition.
AB  - We investigate how fractals evolve into nonfractal behavior as the generation
      process is gradually suppressed. Fractals observed in the conductance of
      semiconductor billiards are of particular interest because the generation process
      is semiclassical and can be suppressed by transitions towards either fully
      classical or fully quantum-mechanical conduction. Investigating a range of
      billiards, we identify a "universal" behavior in the changeover from fractal to
      nonfractal conductance, which is described by a smooth evolution rather than
      deterioration in the fractal scaling properties.

PMID- 11461580
TI  - Observation of a linearly dispersing collective mode in a quantum hall
      ferromagnet.
AB  - Double-layer two-dimensional electron systems can exhibit a fascinating
      collective phase believed to display both quantum ferromagnetism and excitonic
      superfluidity. This unusual phase has recently been found to exhibit tunneling
      phenomena reminiscent of the Josephson effect. A key element of the theoretical
      understanding of this bizarre quantum fluid is the existence of linearly
      dispersing Goldstone collective modes. Using the method of tunneling
      spectroscopy, we have demonstrated the existence of these modes. We find the
      measured velocity to be in reasonable agreement with theoretical estimates.

PMID- 11461581
TI  - Giant anharmonicity and nonlinear electron-phonon coupling in MgB2: a combined
      first-principles calculation and neutron scattering study.
AB  - First-principles calculations of the electronic band structure and lattice
      dynamics for the new superconductor MgB (2) are carried out and found to be in
      excellent agreement with our inelastic neutron scattering measurements. The
      numerical results reveal that the E(2g) in-plane boron phonons near the zone
      center are very anharmonic and strongly coupled to the planar B sigma bands near
      the Fermi level. This giant anharmonicity and nonlinear electron-phonon coupling
      is key to quantitatively explaining the observed high T(c) and boron isotope
      effect in MgB (2).

PMID- 11461582
TI  - Evidence of two distinct dynamic critical exponents in connection with vortex
      physics.
AB  - The dynamic critical exponent z is determined from numerical simulations for the
      three-dimensional (3D) lattice Coulomb gas (LCG) and the 3D XY models with
      relaxational dynamics. It is suggested that the dynamics is characterized by two
      distinct dynamic critical indices z0 and z related to the divergence of the
      relaxation time tau by tau proportional to xi(z0) and tau proportional to k(-z),
      where xi is the correlation length and k the wave vector. The values determined
      are z0 approximately 1.5 and z approximately 1 for the 3D LCG and z0
      approximately 1.5 and z approximately 2 for the 3D XY model. Comparisons with
      other results are discussed.

PMID- 11461583
TI  - Observation of Andreev surface bound states in the 3-K phase region of Sr2RuO4.
AB  - The tunneling spectrum of the superconducting phase with Tc approximately 3.0 K
      has been measured in the Ru-embedded region of Sr2RuO4 using cleaved junctions. A
      sharp zero-bias conductance peak (ZBCP) has been observed below 3 K. All
      characteristics of this ZBCP suggest that it originates from Andreev surface
      bound states, indicating that the pairing in the 3-K phase is also non- s-wave.
      Below the bulk Tc of Sr2RuO4 (approximately 1.5 K), a crossover from sharp to
      bell-shaped ZBCP was found. This supports the theory that there is a phase
      transition in the 3-K phase region near the bulk Tc.

PMID- 11461584
TI  - Superconducting 2D system with lifted spin degeneracy: mixed singlet-triplet
      state.
AB  - Motivated by recent experimental findings, we have developed a theory of the
      superconducting state for 2D metals without inversion symmetry modeling the
      geometry of a surface superconducting layer in a field-effect transistor or near
      the boundary doped by adsorbed ions. In such systems the twofold spin degeneracy
      is lifted by spin-orbit interaction, and singlet and triplet pairings are mixed
      in the wave function of the Cooper pairs. As a result, spin magnetic
      susceptibility becomes anisotropic and Knight shift retains finite and rather
      high value at T = 0.

PMID- 11461585
TI  - Surface-step-induced double magnetic switching of Fe on vicinal W(100).
AB  - Two-level magnetic switching of a bilayer epitaxial Fe film grown on a graded
      stepped W(100) surface is observed using the magneto-optic Kerr effect.
      Hysteresis loops produced by the film at a location on the curved W(100) surface
      corresponding to a vicinal angle of 6.4 degrees exhibit two abrupt jumps in
      magnetization following spin orientation perpendicular to the steps resulting
      from surface-step-induced anisotropy. The two-step process can be understood in
      terms of abrupt depinning of spins in two inequivalent microdomains associated
      with the stepped surface. The results suggest a new realm of ultrathin film
      micromagnetics in which characteristic dimensions of 20-30 A can play a dominant
      role.

PMID- 11461586
TI  - Spin dynamics of the 2D spin 1/2 quantum antiferromagnet copper deuteroformate
      tetradeuterate (CFTD).
AB  - The magnetic excitation spectrum in the two-dimensional (2D) S = 1/2 Heisenberg
      antiferromagnet copper deuteroformate tetradeuterate has been measured for
      temperatures up to T approximately J/2, where J = 6.31+/-0.02 meV is the 2D
      exchange coupling. For T<<J, a dispersion of the zone boundary energy is
      observed, which is attributed to a wave vector dependent quantum renormalization.
      At higher temperatures, spin-wavelike excitations persist, but are found to
      broaden and soften. By combining our data with numerical calculations, and with
      existing theoretical work, a consistent description of the behavior of the model
      system is found over the whole temperature interval investigated.

PMID- 11461587
TI  - Chiral symmetry breaking in magnetic thin films and multilayers.
AB  - A phenomenological theory of chiral symmetry breaking in magnetic nanostructures
      is developed considering induced, inhomogeneous chiral interactions
      (Dzyaloshinsky-Moriya-type). Application of the theory to films and multilayers
      with in-plane and out-of-plane magnetization predicts modulated and two
      dimensional localized patterns (vortices). These new classes of magnetic patterns
      are intrinsically stable and localized on nanometer scale. Various experimental
      observations agree qualitatively with structures derived from this theory.

PMID- 11461588
TI  - Dissipation of intersubband plasmons in wide quantum wells.
AB  - This Letter reports detailed measurements of the dissipation times tau(d) of
      approximately 10 meV intersubband (ISB) plasmons, and of the (single-particle)
      transport lifetimes tau(mu), in a remotely doped 40 nm GaAs quantum well.
      Introduced here as the time for ISB plasmons to dissipate into other modes of the
      electron gas, tau(d) is deduced from the homogeneous ISB absorption linewidth,
      measured as a function of sheet concentration and perpendicular dc electric
      field. Modeling in this and the next Letter [C. A. Ullrich and G. Vignale, Phys.
      Rev. Lett. 87, 037402 (2001)] indicates that scattering from rough interfaces
      dominates tau(d), while scattering from ionized impurities dominates tau(mu).

PMID- 11461589
TI  - Theory of the linewidth of intersubband plasmons in quantum wells.
AB  - Intersubband (ISB) plasmons in remotely doped wide quantum wells acquire a
      linewidth even at zero temperature and in-plane wave vector q(parallel) = 0 by a
      combination of intrinsic (electron-electron interaction) and extrinsic effects
      (impurities and interface roughness). We present a quantitatively accurate theory
      of the linewidth that treats both effects on equal footing and from first
      principles by a combination of time-dependent density-functional theory with the
      memory function formalism. Comparison with recent optical absorption experiments
      shows that the ISB plasmon linewidth has a significant contribution from electron
      electron interaction, and is only weakly related to the mobility.

PMID- 11461590
TI  - Optical anisotropy of oxidized Si(001) surfaces and its oscillation in the layer
      by-layer oxidation process.
AB  - Reflectance-difference (RD) measurements for the oxidation of single-domain (2x1)
      reconstructed Si(001) surfaces show that the polarity of the interface-induced
      optical anisotropy is reversed repeatedly with increasing oxide thickness. The
      oscillation of the RD amplitude, which we show is due to layer-by-layer
      progression of the oxidation, has allowed us to count the number of oxidized Si
      layers in situ during oxidation. The origins of the observed spectral line shape
      are discussed.

PMID- 11461591
TI  - Auger stimulated ion desorption of negative ions via K-capture radioactive decay.
AB  - We report on Auger stimulated ion desorption via Coulomb explosion from surface
      self-assembled alkylthiol and fluorocarbon molecular layers, triggered by K
      capture decay of an imbedded radioactive 55Fe atom. The charge state of the
      ejecta is determined by charge exchange in binary atomic collisions in bulk and
      electron tunneling outside the solid, as well as by fragmentation of
      electronically excited molecules or molecular fragments. We describe the first
      nonbeam experiments documenting positive and abundant negative ion desorption due
      solely to core electron excitation after radioactive decay.

PMID- 11461592
TI  - Dipole blockade and quantum information processing in mesoscopic atomic
      ensembles.
AB  - We describe a technique for manipulating quantum information stored in collective
      states of mesoscopic ensembles. Quantum processing is accomplished by optical
      excitation into states with strong dipole-dipole interactions. The resulting
      "dipole blockade" can be used to inhibit transitions into all but singly excited
      collective states. This can be employed for a controlled generation of collective
      atomic spin states as well as nonclassical photonic states and for scalable
      quantum logic gates. An example involving a cold Rydberg gas is analyzed.

PMID- 11461593
TI  - Coherent control of an atomic collision in a cavity.
AB  - Following a recent proposal by S. B. Zheng and G. C. Guo [Phys. Rev. Lett. 85,
      2392 (2000)], we report an experiment in which two Rydberg atoms crossing a
      nonresonant cavity are entangled by coherent energy exchange. The process,
      mediated by the virtual emission and absorption of a microwave photon, is
      characterized by a collision mixing angle 4 orders of magnitude larger than for
      atoms colliding in free space with the same impact parameter. The final entangled
      state is controlled by adjusting the atom-cavity detuning. This procedure,
      essentially insensitive to thermal fields and to photon decay, opens promising
      perspectives for complex entanglement manipulations.

PMID- 11461594
TI  - Allometric scaling and central source systems.
AB  - Allometric scaling relations abound in nature. Examples include the power law
      relating the metabolic rate of animals and plants to their masses and the power
      law describing the dependence of the size of the drainage basin of a river on the
      total amount of water contained in that river. The exponent is of the form D/D+1,
      where D is the dimension of the system. We show that this scaling exponent is
      simply a consequence of the source distribution of the systems considered and
      requires no further assumptions. To demonstrate the wide range of validity of the
      result we present a simple experiment that shows the predicted behavior in one
      dimension.

PMID- 11461595
TI  - Advective coalescence in chaotic flows.
AB  - We investigate the reaction kinetics of small spherical particles with inertia,
      obeying coalescence type of reaction, B+B-->B, and being advected by
      hydrodynamical flows with time-periodic forcing. In contrast to passive tracers,
      the particle dynamics is governed by the strongly nonlinear Maxey-Riley
      equations, which typically create chaos in the spatial component of the particle
      dynamics, appearing as filamental structures in the distribution of the
      reactants. Defining a stochastic description supported on the natural measure of
      the attractor, we show that, in the limit of slow reaction, the reaction kinetics
      assumes a universal behavior exhibiting a t(-1) decay in the amount of reagents,
      which become distributed on a subset of dimension D2, where D2 is the correlation
      dimension of the chaotic flow.

PMID- 11461596
TI  - Hydrodynamic interactions in quasi-two-dimensional colloidal suspensions.
AB  - The effects of the hydrodynamic interactions on the short-time dynamics of
      colloidal, hard-sphere-like particles confined between two parallel walls are
      measured by digital videomicroscopy. We find that such effects can be described
      in terms of an effective two-dimensional hydrodynamic function H(k), defined as a
      straightforward adaptation to two dimensions of the corresponding object
      describing collective dynamics for the three-dimensional (3D) suspensions.
      Interestingly, the behavior of H(k) is qualitatively similar to the hydrodynamic
      function of 3D suspensions of hard spheres. We also found that for values of k
      where the static structure factor is 1, the dynamics is determined only by self
      diffusion.

PMID- 11461597
TI  - Comment on "neutron brillouin scattering study of collective dynamics in a dense
      He-Ne gaseous mixture".

PMID- 11461599
TI  - Comment on "Real space investigation of the roughening and deconstruction
      transitions of Au(110)".

PMID- 11461601
TI  - Comment on "Self-organized criticality in the Olami-Feder-Christensen model".

PMID- 11461603
TI  - Classification of mixed three-qubit states.
AB  - We introduce a classification of mixed three-qubit states, in which we define the
      classes of separable, biseparable, W, and Greenberger-Horne-Zeilinger states.
      These classes are successively embedded into each other. We show that contrary to
      pure W-type states, the mixed W class is not of measure zero. We construct
      witness operators that detect the class of a mixed state. We discuss the
      conjecture that all entangled states with positive partial transpose (PPTES)
      belong to the W class. Finally, we present a new family of PPTES "edge" states
      with maximal ranks.

PMID- 11461604
TI  - Observation of the quantum zeno and anti-zeno effects in an unstable system.
AB  - We report the first observation of the quantum Zeno and anti-Zeno effects in an
      unstable system. Cold sodium atoms are trapped in a far-detuned standing wave of
      light that is accelerated for a controlled duration. For a large acceleration the
      atoms can escape the trapping potential via tunneling. Initially the number of
      trapped atoms shows strong nonexponential decay features, evolving into the
      characteristic exponential decay behavior. We repeatedly measure the number of
      atoms remaining trapped during the initial period of nonexponential decay.
      Depending on the frequency of measurements we observe a decay that is suppressed
      or enhanced as compared to the unperturbed system.

PMID- 11461605
TI  - Fluctuations in stationary nonequilibrium states of irreversible processes.
AB  - We formulate a dynamical fluctuation theory for stationary nonequilibrium states
      (SNS) which covers situations in a nonlinear hydrodynamic regime and is verified
      explicitly in stochastic models of interacting particles. In our theory a crucial
      role is played by the time reversed dynamics. Our results include the
      modification of the Onsager-Machlup theory in the SNS, a general Hamilton-Jacobi
      equation for the macroscopic entropy and a nonequilibrium, nonlinear fluctuation
      dissipation relation valid for a wide class of systems.

PMID- 11461606
TI  - Quantum discontinuity between zero and infinitesimal graviton mass with a Lambda
      term.
AB  - We show that the recently demonstrated absence of the usual discontinuity for
      massive spin 2 with a Lambda term is an artifact of the tree approximation, and
      that the discontinuity reappears at one loop.

PMID- 11461607
TI  - Large extra dimensions, sterile neutrinos and solar neutrino data.
AB  - Solar, atmospheric, and LSND neutrino oscillation results require a light sterile
      neutrino, nu(B), which can exist in the bulk of extra dimensions. Solar nu(e),
      confined to the brane, can oscillate in the vacuum to the zero mode of nu(B) and
      via successive Mikheyev-Smirnov-Wolfenstein transitions to Kaluza-Klein states of
      nu(B). This new way to fit solar data is provided by both low and intermediate
      string scale models. From average rates seen in the three types of solar
      experiments, the Super-Kamiokande spectrum is predicted with 73% probability, but
      dips characteristic of the 0.06 mm extra dimension should be seen in the SNO
      spectrum.

PMID- 11461608
TI  - Observation of an anomalous number of dimuon events in a high energy neutrino
      beam.
AB  - A search for long-lived neutral particles ( N0's) with masses above 2.2 GeV/c(2)
      that decay into at least one muon has been performed using an instrumented decay
      channel at the NuTeV experiment at Fermilab. Data were examined for particles
      decaying into the final states mumu, mu(e), and mu(pi). Three mumu events were
      observed over an expected standard model background of 0.069+/-0.010 events; no
      events were observed in the other modes.

PMID- 11461609
TI  - Calorons and localization of quark eigenvectors in lattice QCD.
AB  - We analyze the localization properties for eigenvectors of the Dirac operator in
      quenched lattice QCD in the vicinity of the deconfinement phase transition.
      Studying the characteristic differences between the Z3 sectors above the critical
      temperature T(c), we find indications for the presence of calorons.

PMID- 11461610
TI  - Radiative proton capture on (6)He.
AB  - Radiative capture of protons is investigated as a probe of clustering in nuclei
      far from stability. The first such measurement on a halo nucleus is reported here
      for the reaction 6He(p,gamma) at 40 MeV. Capture into 7Li is observed as the
      strongest channel. In addition, events have been recorded that may be described
      by quasifree capture on a halo neutron, the alpha core, and 5He. The possibility
      of describing such events by capture into the continuum of 7Li is also discussed.

PMID- 11461611
TI  - Nuclear polarization of hydrogen molecules from recombination of polarized atoms.
AB  - The nuclear polarization of H(2) molecules formed by recombination of polarized H
      atoms on a Cu surface was measured as a function of external magnetic field and
      of temperature of the surface. The proton polarization of the molecules was
      determined by scattering of a longitudinally polarized 203-MeV proton beam in the
      Indiana University Cyclotron Facility storage ring. The nuclear polarization of
      the molecules, relative to the polarization of the atoms before recombination,
      increased from near zero in a weak magnetic field to 0.42 +/- 0.02 in a 0.66 T
      field. A simple model of the relaxation accounts quantitatively for the
      observations.

PMID- 11461612
TI  - Microwave ionization of an atomic electron wave packet.
AB  - A short microwave pulse is used to ionize a lithium Rydberg wave packet launched
      from the core at a well-defined phase of the field. We observe a strong
      dependence on the relative phase between the motion of the wave packet and the
      oscillations of the field. This phase dependent ionization is also studied as a
      function of the relative frequency. Our experimental observations are in good
      qualitative agreement with a one-dimensional classical model of wave packet
      ionization.

PMID- 11461613
TI  - Use of the relative phase in a bichromatic field pulse to control a quasienergy
      gap.
AB  - We show experimentally and theoretically how the relative phase in a short,
      linearly polarized microwave pulse consisting of two phase-locked frequencies is
      effective for strong-field quantum control of He Rydberg atoms when the frequency
      ratio p:q is 3:1. It is also effective when p:q = 2:1 but less effective for 3:2.
      Parameters in our experiment are similar to those investigating quantum control
      of tightly bound atoms or molecules with ultrashort pulsed lasers.

PMID- 11461614
TI  - Separation of recollision mechanisms in nonsequential strong field double
      ionization of Ar: the role of excitation tunneling.
AB  - Vector momentum distributions of two electrons created in double ionization of Ar
      by 25 fs, 0.25 PW/cm(2) laser pulses at 795 nm have been measured using a
      "reaction microscope." At this intensity, where nonsequential ionization
      dominates, distinct correlation patterns are observed in the two-electron
      momentum distributions. A kinematical analysis of these spectra within the
      classical "recollision model" revealed an (e,2e)-like process and excitation with
      subsequent tunneling of the second electron as two different ionization
      mechanisms. This allows a qualitative separation of the two mechanisms
      demonstrating that excitation-tunneling is the dominant contribution to the total
      double ionization yield.

PMID- 11461615
TI  - Optimization of ground- and excited-state wave functions and van der Waals
      clusters.
AB  - A quantum Monte Carlo method is introduced to optimize excited-state trial wave
      functions. The method is applied in a correlation function Monte Carlo
      calculation to compute ground- and excited-state energies of bosonic van der
      Waals clusters of up to seven particles. The calculations are performed using
      trial wave functions with general three-body correlations.

PMID- 11461616
TI  - Nonlinear Aharonov-Bohm scattering by optical vortices.
AB  - We study linear and nonlinear wave scattering by an optical vortex in a self
      defocusing nonlinear Kerr medium. In the linear case, we find a splitting of a
      plane-wave front at the vortex proportional to its circulation, similar to what
      occurs in the scattered wave of electrons for the Aharonov-Bohm effect. For
      larger wave amplitudes, we study analytically and numerically the scattering of a
      dark-soliton stripe (a nonlinear analog of a small-amplitude wave packet) by a
      vortex and observe a significant asymmetry of the scattered wave. Subsequently, a
      wave-front splitting of the scattered wave develops into transverse modulational
      instability, "unzipping" the stripe into trains of vortices with opposite
      charges.

PMID- 11461617
TI  - Kerr spatiotemporal self-focusing in a planar glass waveguide.
AB  - We observed simultaneous focusing in both space and time for light pulses
      propagating in a planar waveguide. In particular, 60 fs pulses with a width of
      170 microm were injected into a planar glass waveguide in the anomalous
      dispersion regime. Output pulses as short as 30 fs and as narrow as 20 microm
      were measured. The results suggest that multiphoton absorption and intrapulse
      stimulated Raman scattering arrest the spatiotemporal contraction. The results
      were compared to the pulse evolution in zero and normal dispersion regimes and
      were shown to be significantly different. All of the experimental results were
      reproduced by a numerical model.

PMID- 11461618
TI  - Mechanisms of ultrasonic modulation of multiply scattered coherent light: an
      analytic model.
AB  - An analytic model of the ultrasonic modulation of multiply scattered coherent
      light in scattering media is developed based on two mechanisms: the ultrasonic
      modulation of the index of refraction and the ultrasonic modulation of the
      displacements of Rayleigh scatterers. In water solutions, for example, the first
      mechanism is slightly less important than the second mechanism when the
      scattering mean free path is less than a critical fraction (0.0890) of the
      acoustic wavelength, and it becomes increasingly more important beyond this
      point. This model agrees well with an independent Monte Carlo model.

PMID- 11461619
TI  - Detecting phase synchronization in a chaotic laser array.
AB  - Detection of phase synchronization of coupled chaotic oscillators is examined
      experimentally for the case of a linear laser array. Phase variables are computed
      by applying a Gaussian filter, peaked at a positive frequency, to the signal
      obtained from the intensity time series of the individual lasers. Relationships
      between different frequency components of the oscillator dynamics that are not
      otherwise apparent are unambiguously detected.

PMID- 11461620
TI  - Resolving clusters in chaotic ensembles of globally coupled identical
      oscillators.
AB  - Clustering in ensembles of globally coupled identical chaotic oscillators is
      reconsidered using a twofold approach. Stability of clusters towards "emanation"
      of the elements is described with the evaporation Lyapunov exponents. It appears
      that direct numerical simulations of ensembles often lead to spurious clusters
      that have positive evaporation exponents, due to a numerical trap. We propose a
      numerical method that surmounts the spurious clustering. We also demonstrate that
      clustering can be very sensitive to the number of elements in the ensemble.

PMID- 11461621
TI  - Universal distribution of centers and saddles in two-dimensional turbulence.
AB  - The statistical properties of the local topology of two-dimensional turbulence
      are investigated using an electromagnetically forced soap film. The local
      topology of the incompressible 2D flow is characterized by the Jacobian
      determinant Lambda(x,y) = 1 / 4(omega(2)-sigma(2)), where omega(x,y) is the local
      vorticity and sigma(x,y) is the local strain rate. For turbulent flows driven by
      different external force configurations, P(Lambda) is found to be a universal
      function when rescaled using the turbulent intensity. A simple model that agrees
      with the measured functional form of P(Lambda) is constructed using the
      assumption that the stream function, psi(x,y), is a Gaussian random field.

PMID- 11461622
TI  - Stability of periodically focused intense particle beams.
AB  - A stability analysis of periodically focused intense particle beams based on the
      beam envelope equation is performed. We show that (i) the scenario, as the
      focusing field increases, is not the existence of a single threshold above which
      stable matched (equilibrium) solutions are absent, as generally believed, but the
      existence of successive regions of stability interrupted by gaps of instability;
      (ii) the beam can be focused to tighter radii using new stable matched solutions
      found for focusing field strengths greater than the previous threshold. Self
      consistent simulations validate the findings.

PMID- 11461623
TI  - Transport processes in reversed-field-pinch plasmas: inconsistency with the self
      organized-criticality paradigm.
AB  - A statistical analysis of the anomalous particle flux in the edge region of the
      RFX experiment has revealed that laminar times between bursts, which account for
      more than 50% of the losses, have a power law distribution and that flux
      fluctuations are not self-similar. These properties are found in contrast with a
      wide class of self-organized-criticality models so that it is concluded that
      there is no experimental evidence of avalanchelike process occurrence in the
      plasma of RFX.

PMID- 11461624
TI  - Ionization balance in inertial confinement fusion hohlraums.
AB  - We present the first x-ray spectroscopic measurements of the ionization balance
      in inertial confinement fusion hohlraums supported by 4omega Thomson scattering
      diagnostics. The experimental data show agreement with non-LTE radiation
      hydrodynamic calculations of the averaged Au charge state and electron
      temperatures. These findings are consistent with the successful integrated
      modeling of the hohlraum radiation fields. Comparisons with detailed synthetic
      spectra calculations show that the experimental ionization distribution is
      slightly shifted indicating nonsteady state kinetics.

PMID- 11461625
TI  - Direct observation of localized parallel electric fields in a space plasma.
AB  - We report direct measurements of parallel electric fields related to particle
      acceleration in a collisionless space plasma. The electric field is that of a
      monotonic potential ramp localized to approximately 10 debye lengths along the
      magnetic field. Electrons accelerated by the parallel electric field are
      accompanied by intense electrostatic waves and nonlinear structures interpreted
      as electron phase-space holes.

PMID- 11461626
TI  - Effect of 3He on submonolayer superfluidity.
AB  - We have studied the superfluid response of 3He-4He mixture films adsorbed onto
      porous gold for a wide range of 3He and 4He coverages, focusing on submonolayer
      superfluidity. At T = 0, 3He appears to float on top of 4He and can be viewed as
      a second substrate that induces its own inert layer. Depending on the 4He
      content, the zero-temperature superfluid mass and the superfluid onset
      temperature either saturate or vanish with the addition of 3He. The T = 0
      superfluid-insulator phase boundary, which can be described by a simple function,
      is found in the 3He-4He coverage plane.

PMID- 11461627
TI  - Phase-field model of mode III dynamic fracture.
AB  - We introduce a phenomenological continuum model for the mode III dynamic fracture
      that is based on the phase-field methodology used extensively to model
      interfacial pattern formation. We couple a scalar field, which distinguishes
      between "broken" and "unbroken" states of the system, to the displacement field
      in a way that consistently includes both macroscopic elasticity and a simple
      rotationally invariant short-scale description of breaking. We report two
      dimensional simulations that yield steady-state crack motion in a strip geometry
      above the Griffith threshold.

PMID- 11461628
TI  - Silicon antisite in 4H SiC.
AB  - Electron paramagnetic resonance spectrum with C(3V) symmetry and a spin S = 1/2
      has been observed in p-type, electron-irradiated 4H SiC. Based on the observed
      29Si hyperfine structures it is suggested that the defect is the isolated silicon
      antisite (Si(C)). The spin S = 1/2 and the observation of the defect only in p
      type material suggest that the Si(C) is in the positive-charge state. A strong
      temperature dependence of the g value and hyperfine coupling constant of the
      Si(C)(+) center indicates a considerable lattice relaxation in the vicinity of
      the defect.

PMID- 11461629
TI  - Metal-encapsulated fullerenelike and cubic caged clusters of silicon.
AB  - We report metal-encapsulated caged clusters of silicon from ab initio
      pseudopotential plane wave calculations using generalized gradient approximation
      for the exchange-correlation energy. Depending upon the size of the metal ( M)
      atom, silicon forms fullerenelike M@Si(16), M = Hf, Zr, and cubic M@Si(14), M =
      Fe, Ru, Os, caged clusters. The embedding energy of the M atom is approximately
      12 eV due to strong M-Si interactions that make the cage compact. Bonding in
      these clusters is predominantly covalent and the highest-occupied-lowest
      unoccupied molecular orbital gap is approximately 1.5 eV. However, an
      exceptionally large gap (2.35 eV) is obtained for Ti@Si(16) Frank-Kasper
      polyhedron. Interaction between these clusters is weak, making them attractive
      for cluster-assembled materials.

PMID- 11461630
TI  - Do arsenic interstitials really exist in As-rich GaAs?
AB  - To investigate the lattice distortion caused by point defects in As-rich GaAs, we
      make use of a self-consistent-charge density-functional based tight-binding
      method. Both relevant defects, the As antisite and the As interstitial, cause
      significant lattice distortion. In contrast to As interstitials, isolated As
      antisites lead to lattice strain as well as displacement of nearest neighbor As
      lattice atoms into the <110> channels, in excellent agreement with experiments.
      Therefore, our result gives powerful evidence for As antisites being the
      dominating defect in as-grown As-rich GaAs.

PMID- 11461631
TI  - Critical coarsening without surface tension: the universality class of the voter
      model.
AB  - We show that the two-dimensional voter model, usually considered to be only a
      marginal coarsening system, represents a broad class of models for which phase
      ordering takes place without surface tension. We argue that voter-like growth is
      generically observed at order-disorder nonequilibrium transitions solely driven
      by interfacial noise between dynamically symmetric absorbing states.

PMID- 11461632
TI  - Surface patterns of laterally extended thin liquid films in three dimensions.
AB  - We examine the fully nonlinear behavior of a thin liquid film in three spatial
      dimension for a large lateral extension. A partial differential equation is used
      for the spatiotemporal evolution of the height of the film. To take
      intermolecular forces in the liquid into account, we concentrate on a recently
      formulated model of Pismen and Pomeau, who derived an expression for the
      disjoining pressure only from the wetting properties of the fluid. Finally, the
      motion of a falling film on an inclined plane is studied within this model.

PMID- 11461633
TI  - Quantum hall plateau transition at order 1/N.
AB  - The localization behavior of noninteracting two-dimensional electrons in a random
      potential and strong magnetic field is of fundamental interest for the physics of
      the quantum Hall effect. In order to understand the emergence of power-law
      delocalization near the discrete extended-state energies E(n) = Planck's over
      2piomega(c)(n+1 / 2), we study a generalization of the disorder-averaged
      Liouvillian framework for the lowest Landau level to N flavors of electron
      densities ( N = 1 for the physical case). We find analytically the large- N limit
      and 1/N corrections for all disorder strengths: at N = infinity this gives an
      estimate of the critical conductivity, and at order 1/N an estimate of the
      localization exponent nu.

PMID- 11461634
TI  - Direct link between Coulomb blockade and shot noise in a quantum-coherent
      structure.
AB  - We analyze the current-voltage characteristic of a quantum conduction channel
      coupled to an electromagnetic environment with arbitrary frequency-dependent
      impedance. In the weak blockade regime the correction to the Ohmic behavior is
      directly related to the channel current fluctuations, vanishing at perfect
      transmission in the same way as shot noise. This relation can be generalized to
      describe the environmental Coulomb blockade in a generic mesoscopic conductor
      coupled to an external impedance, as the response of the latter to the current
      fluctuations in the former.

PMID- 11461635
TI  - Effects of stochastic webs on chaotic electron transport in semiconductor
      superlattices.
AB  - We investigate chaotic electron transport in the lowest miniband of a
      semiconductor superlattice with a tilted magnetic field. This experimentally
      accessible non-Kolmogorov-Arnol'd-Moser system involves only stationary electric
      and magnetic fields, but is dynamically equivalent to a time-dependent kicked
      harmonic oscillator. The onset of chaos strongly delocalizes the electron orbits,
      thus raising the electrical conductivity. When the cyclotron and Bloch
      frequencies are commensurate, the phase space is threaded by a stochastic web,
      which produces a further resonant increase in the conductivity.

PMID- 11461636
TI  - Specific heat of Mg11B2: evidence for a second energy gap.
AB  - Measurements of the specific heat of Mg11B2 from 1 to 50 K, in magnetic fields to
      9 T, give the Debye temperature, Theta = 1050 K, the coefficient of the normal
      state electron contribution, gamma(n) = 2.6 mJ mol(-1) K-2, and a discontinuity
      in the zero-field specific heat of 133 mJ mol(-1) K-1 at T(c) = 38.7 K. The
      estimated value of the electron-phonon coupling parameter, lambda = 0.62, could
      account for the observed T(c) only if the important phonon frequencies are
      unusually high relative to Theta. At low T, there is a strongly field-dependent
      feature that suggests the existence of a second energy gap, about 4 times smaller
      than the major gap.

PMID- 11461637
TI  - Anisotropy of superconducting MgB2 as seen in electron spin resonance and
      magnetization data.
AB  - We observed the conduction electron spin resonance (CESR) in fine powders of MgB2
      both in the superconducting and normal states. The Pauli susceptibility is chi(s)
      = 2.0 x 10(-5) emu/mole in the temperature range of 450 to 600 K. The spin
      relaxation rate has an anomalous temperature dependence. The CESR measured below
      T(c) at several frequencies suggests that MgB2 is a strongly anisotropic
      superconductor with the upper critical field, H(c2), ranging between 2 and 16 T.
      The high-field reversible magnetization data of a randomly oriented powder sample
      are well described assuming that MgB2 is an anisotropic superconductor with
      H(ab)(c2)/H(c)(c2) approximately 6-9.

PMID- 11461638
TI  - Band-structure trend in hole-doped cuprates and correlation with T(c max).
AB  - By calculation and analysis of the bare conduction bands in a large number of
      hole-doped high-temperature superconductors, we have identified the range of the
      intralayer hopping as the essential, material-dependent parameter. It is
      controlled by the energy of the axial orbital, a hybrid between Cu 4s, apical
      oxygen 2p(z), and farther orbitals. Materials with higher T(c max) have larger
      hopping ranges and axial orbitals more localized in the CuO2 layers.

PMID- 11461639
TI  - Universality class of the Nishimori point in the 2D +/- J random-bond Ising
      model.
AB  - We study the universality class of the Nishimori point in the 2D +/- J random
      bond Ising model by means of the numerical transfer-matrix method. Using the
      domain-wall free energy, we locate the position of the fixed point along the
      Nishimori line at the critical concentration value p(c) = 0.1094 +/- 0.0002 and
      estimate nu = 1.33 +/- 0.03. Then, we obtain the exponents for the moments of the
      spin-spin correlation functions as well as the value for the central charge c =
      0.464 +/- 0.004. The main qualitative result is the fact that percolation is now
      excluded as a candidate for describing the universality class of this fixed
      point.

PMID- 11461640
TI  - Strong damping of phononic heat current by magnetic excitations in SrCu2(BO3)(2).
AB  - Measurements of the thermal conductivity as a function of temperature and
      magnetic field in the 2D dimer spin system SrCu2(BO3)(2) are presented. In zero
      magnetic field the thermal conductivity along and perpendicular to the magnetic
      planes shows a pronounced double-peak structure as a function of temperature. The
      low-temperature maximum is drastically suppressed with increasing magnetic field.
      Our quantitative analysis reveals that the heat current is due to phonons and
      that the double-peak structure arises from pronounced resonant scattering of
      phonons by magnetic excitations.

PMID- 11461641
TI  - Cluster algorithms for general-S quantum spin systems.
AB  - We present a general strategy to extend quantum cluster algorithms for S = 1 / 2
      spin systems, such as the loop algorithm, to those with an arbitrary size of
      spins. The partition function of a high- S spin system is generally represented
      by the path integral of a S = 1 / 2 model with special boundary conditions in the
      imaginary-time direction. We introduce additional graphs for the boundary part
      and give the labeling probability explicitly, which completes the algorithm
      together with an existing S = 1 / 2 algorithm. As a demonstration, we simulate
      the integer-spin antiferromagnetic Heisenberg chains. The magnitude of the first
      excitation gap is estimated to be 0.41048(6), 0.08917(4), and 0.01002(3) for S =
      1, 2, and 3, respectively.

PMID- 11461642
TI  - Single hole motion in LaMnO3.
AB  - We study single hole motion in LaMnO3 using the classical approximation for Jahn
      Teller lattice distortions, a modified Lang-Firsov approximation for dynamical
      breathing-mode phonons, and the self-consistent Born approximation (verified by
      exact diagonalization) for hole-orbital-excitation scattering. We show that in
      the realistic parameter space for LaMnO3, quantum effects of electron-phonon
      interaction are small. The quasiparticle bandwidth is about 2.2J in the purely
      orbital t-J model. It is strikingly broadened to be of order t by strong static
      Jahn-Teller lattice distortions even when the polaronic band narrowing is taken
      into account.

PMID- 11461643
TI  - Spin correlations in Ho2Ti2O7: a dipolar spin ice system.
AB  - The pyrochlore material Ho2Ti2O7 has been suggested to show "spin ice" behavior.
      We present neutron scattering and specific heat results that establish
      unambiguously that Ho2Ti2O7 exhibits spin ice correlations at low temperature.
      Diffuse magnetic neutron scattering is quite well described by a nearest neighbor
      spin ice model and very accurately described by a dipolar spin ice model. The
      heat capacity is well accounted for by the sum of a dipolar spin ice contribution
      and an expected nuclear spin contribution, known to exist in other Ho3+ salts.
      These results settle the question of the nature of the low temperature spin
      correlations in Ho2Ti2O7 for which contradictory claims have been made.

PMID- 11461644
TI  - Observation of the x-ray magneto-optical Voigt effect.
AB  - The existence of the x-ray magneto-optical Voigt effect is demonstrated. By means
      of polarization analysis the Voigt rotation and ellipticity of linearly polarized
      synchrotron radiation are measured at the Co L3 edge upon transmission through an
      amorphous Co film. The observed x-ray Voigt rotation is about 7.5 degrees
      /microm. On the basis of ab initio calculations it is shown that the x-ray Voigt
      effect follows sensitively the amount of spin polarization of the 2p core states.
      Therefore it provides a unique measure of the spin splitting of the core states.

PMID- 11461645
TI  - Observation of the 22.5-keV resonance in (149)Sm by the nuclear lighthouse
      effect.
AB  - We have observed coherent nuclear resonant scattering of synchrotron radiation at
      the 22.5-keV resonance of (149)Sm. High-speed rotational sample motion led to an
      angular deflection of the resonantly scattered radiation off the nonresonant
      primary beam. This allowed us to determine the resonance energy of the first
      excited nuclear level of (149)Sm to be 22496(4) eV. Because of the angular
      deflection of the resonant photons, time spectra of coherent nuclear resonant
      scattering can be recorded as a function of a spatial coordinate. Time
      resolutions of a few 10 ps can be expected, which are beyond the limits of
      existing x-ray detection schemes.

PMID- 11461646
TI  - Good dynamics versus bad kinematics: is entanglement needed for quantum
      computation?
AB  - We study the role of entanglement in quantum computation. We consider the case of
      a pure state contaminated by "white noise." This framework arises, for example,
      in pseudopure state implementations of quantum computing using NMR. We analyze
      quantum computational protocols which aim to solve exponential classical problems
      with polynomial resources and ask whether or not entanglement of the pseudopure
      states is needed to achieve this aim. We show that, for a large class of such
      protocols, including Shor's factorization, entanglement is necessary. We also
      show that achieving entanglement is not sufficient: If the state is sufficiently
      noisy, exponential resources are needed even if entanglement is present.

PMID- 11461647
TI  - Why circadian rhythms are circadian: competitive population dynamics of
      biological oscillators.
AB  - Living creatures are under control of biological clocks with various periods near
      those of environmental cycles. Examples are circadian (about a day) and
      circannual (about a year) clocks. We may ask why their periods are not precisely
      one day or one year because adaptation to the environment should then be easier.
      Here, introducing a model of competitive population dynamics of biological
      species with clock dynamics incorporated, it is shown that periods equal or close
      to that of the environment do not always guarantee overwhelming superiority and
      can even lead to extinction. This result may provide a clue to solve the mystery.

PMID- 11461648
TI  - Structural and cohesive properties of a C60 monolayer.
AB  - We have explored the cohesive property of a monolayer of C (60) molecules (ML- C
      (60)) by means of total energy calculations with the density-functional theory.
      The total energy curve calculated for ML- C (60), which is obtained as a function
      of the lattice constant, has two minima and shows a hysteresis in the compression
      tension stroke. These two minima in energy correspond to the different structural
      phases of ML- C (60): one is a monomer phase and the other is a polymer one. The
      energy band gap within the framework of the local density approximation varies
      from 1 eV (semiconducting phase) to 0 eV (metallic phase) with external pressure
      and without structural transition from the monomer phase to the polymer one.

PMID- 11461649
TI  - Tip streaming from a drop in the presence of surfactants.
AB  - Drop breakup in a linear extensional flow is simulated numerically using a
      nonlinear model for the surface tension that accounts for maximum packing at the
      interface. Surface convection sweeps surfactant to the drop poles, where it
      accumulates and drives the surface tension to near zero. The drop assumes a
      transient shape with highly pointed tips. From these tips, thin liquid threads
      are pulled. Subsequently, small, surfactant-rich droplets are emitted from the
      termini of these threads. The scale of the shed drops depends on the initial
      surfactant coverage. Dilute initial coverage leads to tip streaming, while high
      initial coverage leads to the tip dropping breakup mode.

PMID- 11461650
TI  - Evidence of shear-induced fluid fracture in telechelic polymer networks.
AB  - The shear-flow properties of telechelic polymer networks have been investigated
      by rheology and flow-visualization techniques. The steady-shear viscosity versus
      shear-rate curves exhibits two main branches separated by a discontinuity. One
      branch of the flow curve is Newtonian and shear thickening, whereas the second
      one is shear thinning. Above the discontinuity, shear induces a fluid fracture
      similar to those reported for brittle solids and at the origin of an
      inhomogeneous flow. Because of the finite relaxation time of the polymer network
      however, and contrary to ordinary gels, the fracture can be created and healed
      reversibly.

PMID- 11461651
TI  - Oscillatory driving of crystal surfaces: a route to controlled pattern formation.
AB  - We show that the oscillatory driving of crystal surfaces can induce pattern
      formation or smoothening. Depending on driving conditions, step bunching and
      meandering, mound formation, or surface smoothening may be seen in the presence
      of a kinetic asymmetry at the steps or kinks. We employ a step model to calculate
      the induced mass flux along misoriented surfaces, which accounts for surface
      dynamics and stability. Slope selection, surface metastability, and frequency
      dependent surface stability are found. Quantitative predictions for pattern
      formation on metal surfaces in an electrolyte are provided.

PMID- 11461652
TI  - Comment on "spin relaxation in quantum hall systems".

PMID- 11461654
TI  - A multi-center analysis of rehospitalizations five years after brain injury.
AB  - OBJECTIVE: To investigate the incidence and cause of rehospitalizations 1 and 5
      years after traumatic brain injury. DESIGN: Descriptive statistics were computed
      in a prospective study of the cause and incidence of rehospitalizations at years
      1 and 5 after injury. Analysis of variance and chi-square tests were used to
      identify factors relating to rehospitalization; factors included length of stay,
      admission and discharge functional status, payer source, medical complications,
      injury severity, and demographics. SETTING: Seventeen medical centers in the
      federally sponsored Traumatic Brain Injury Model Systems. In each setting, the
      continuum of care includes emergency medical services, intensive and acute
      medical care, inpatient rehabilitation, and a spectrum of community
      rehabilitation services. PARTICIPANTS: Eight hundred ninety-five rehabilitation
      patients admitted to acute care within 24 hours of traumatic brain injury between
      1989 and 1999 were examined at 1-year follow-up. MAIN OUTCOME MEASURES: Incidence
      and cause of rehospitalization at 1 and 5 years after injury. RESULTS: The
      incidence of rehospitalization ranged from 22.9% 1 year after injury to 17.0% at
      5 years after injury. At 1 year after injury, a third of the rehospitalizations
      were for elective reasons. At 5 years after injury, the incidence of readmissions
      for seizures and psychiatric difficulties and general health maintenance
      increased substantially. T-tests and chi-square analyses were performed on the 5
      year follow-up data to compare those rehospitalized for unplanned reasons with
      those not rehospitalized. CONCLUSIONS: There remains a relatively high rate of
      rehospitalization in the long term after traumatic brain injury. The costs of
      rehospitalization should be considered when evaluating the long-term consequences
      of injury.

PMID- 11461655
TI  - Long-term recovery course after traumatic brain injury: a comparison of the
      functional independence measure and disability rating scale.
AB  - OBJECTIVES: To study group changes over time after traumatic brain injury (TBI).
      DESIGN: Prospective cohort. SETTING AND PARTICIPANTS: TBI Model System Database
      with 1160 subjects using cohort with complete data. MAIN OUTCOME MEASURES:
      Functional Independence Measure (FIM) and Disability Rating Scale (DRS) at
      rehabilitation discharge and annually after injury. RESULTS: Statistically
      significant differences existed between FIM-total, FIM-Motor, FIM-Cognitive
      subscales, and DRS at rehabilitation discharge and year 1. Comparisons of year-to
      year intervals, years 1 and 3, 1 and 5, and 3 and 5, revealed no statistically
      significant differences except between years 1 and 3 and 1 and 5 with DRS, and
      years 1 and 5 with FIM. Including only those more dependent at year 1 revealed
      statistically significant differences between years 1 and 2 and 1 and 5 on FIM
      Cognitive and DRS, but not the FIM-Motor. The proportion of change for FIM and
      DRS items from year 1 to years 2 and 5 revealed DRS Level of Functioning and
      Employability items accounted for most DRS change, whereas FIM change was more
      spread across its components. CONCLUSIONS: DRS is more sensitive to changes
      during a shorter time period than FIM and seems to be more appropriate for
      detecting long-term deficits. However, research studies aimed at detecting
      meaningful changes year to year after TBI may need to use other tools or consider
      changes among individuals instead of group changes. DRS Level of Function and
      Employability Items represent complex functions expected to recover later than
      the more basic DRS items. Sole use of these two DRS items might provide an
      efficient means of measuring long-term recovery when resources are limited,
      whereas expansion of these two items might allow greater sensitivity and detail.

PMID- 11461656
TI  - Factors associated with perceived quality of life many years after traumatic
      brain injury.
AB  - OBJECTIVES: To explore factors associated with perceived quality of life (QOL) 8
      to 24 years after traumatic brain injury (TBI). DESIGN: Retrospective cohort
      study. PARTICIPANTS: Two hundred seventy-five individuals who sustained moderate
      to severe TBI who were discharged from a rehabilitation hospital participated in
      this study. We interviewed consenting participants up to 24 years after injury.
      OUTCOME MEASURES: Self-rated Quality of Life Scale. RESULTS: Multivariate linear
      regression analyses revealed that perceived mental health, self-rated health,
      gender (women rating QOL higher), participation in work and leisure, and the
      availability of emotional support were significantly associated with QOL (P
      <.05). CONCLUSION: The importance of designing ongoing support programs to
      further reintegrate TBI survivors several years after injury is discussed.

PMID- 11461657
TI  - Long-term neuropsychological outcome after traumatic brain injury.
AB  - OBJECTIVE: To describe neuropsychological outcome 5 years after injury in persons
      with traumatic brain injury (TBI) who received inpatient medical rehabilitation.
      To determine the magnitude and pattern neuropsychological recovery from 1 year to
      5 years after injury. DESIGN: Longitudinal cohort study with inclusion based on
      the availability of neuropsychological data at 1 year and 5 years after injury.
      SETTING: National Institute on Disability and Rehabilitation Research Traumatic
      Brain Injury Model Systems of Care. PARTICIPANTS: One hundred eighty-two persons
      with complicated mild to severe traumatic brain injury. PRIMARY OUTCOME MEASURES:
      Digits Forward and Backward, Logical Memory I and II, Token Test, Controlled Oral
      Word Association Test, Symbol Digit Modalities Test, Trail Making Test, Rey
      Auditory Verbal Learning Test, Visual Form Discrimination, Block Design,
      Wisconsin Card Sorting Test, and Grooved Pegboard. RESULTS: Significant
      variability in outcome was found 5 years after TBI, ranging from no measurable
      impairment to severe impairment on neuropsychological tests. Improvement from 1
      year after injury to 5 years was also variable. Using the Reliable Change Index,
      22.2% improved, 15.2% declined, and 62.6% were unchanged on test measures.
      CONCLUSIONS: Neuropsychological recovery after TBI is not uniform across
      individuals and neuropsychological domains. For a subset of persons with moderate
      to severe TBI, neuropsychological recovery may continue several years after
      injury with substantial recovery. For other persons, measurable impairment
      remains 5 years after injury. Improvement was most apparent on measures of
      cognitive speed, visuoconstruction, and verbal memory.

PMID- 11461658
TI  - Long-term maintenance of gains obtained in postacute rehabilitation by persons
      with traumatic brain injury.
AB  - OBJECTIVE: To investigate maintenance of gains after discharge from a postacute
      rehabilitation program. DESIGN: Longitudinal cohort study, with inclusion based
      on availability of subjects at three time points. SETTING: Comprehensive
      postacute rehabilitation program in the Southern United States. PARTICIPANTS:
      Thirty-four persons with medically documented complicated mild to severe
      traumatic brain injury; primarily male Caucasians with some college. MAIN OUTCOME
      MEASURES: Disability Rating Scale and the Community Integration Questionnaire
      completed at admission, discharge, and two follow-up time points. RESULTS:
      Repeated measures analyses, using time from injury to discharge as a covariate,
      revealed significant improvements on all measures from admission to discharge,
      with no significant change from discharge to either of the follow-up periods.
      However, substantial changes were noted in individual cases. CONCLUSIONS: The
      results indicate that gains made by persons with traumatic brain injury during
      postacute rehabilitation are generally maintained at long-term follow-up, but
      changes occur in individual cases. Long-term services may help prevent decline in
      individual cases.

PMID- 11461659
TI  - Long-term life quality and family needs after traumatic brain injury.
AB  - OBJECTIVES: This investigation assessed the life quality and long-term family
      needs of caregivers of persons with brain injury. DESIGN: Respondents completed
      the Virginia Traumatic Brain Injury Family Needs Assessment Survey. SETTING:
      Community-based sample. PARTICIPANTS: Respondents included 57 caregivers of
      persons with traumatic brain injury who were at least 4 years after injury and
      who resided in Virginia. Respondents ranged in age from 19 to 82 years and were
      primarily women and Caucasian. OUTCOME MEASURES: The Family Needs Questionnaire
      (FNQ) and quality of life questions. RESULTS: Results indicate diminished life
      quality after injury. With regard to family needs, Health Information (51.43%)
      and Involvement with Care (47.93%) needs were most often rated as met.
      Instrumental Support (31.52%) and Professional Support (28.38%) needs were most
      often rated as not met. CONCLUSIONS: Family needs and support systems for those
      needs change over time. This investigation provides evidence that unmet family
      needs extend well beyond the acute setting and that caregiver life quality
      diminishes over time. The importance of appreciating long-term family needs and
      other life quality issues should not be underestimated.

PMID- 11461660
TI  - The current status of electrophysiologic procedures for the assessment of mild
      traumatic brain injury.
AB  - DESIGN: This review examines studies that used spontaneous electroencephalography
      (EEG), evoked potentials (EP), event-related potentials (ERP), and
      magnetoencephalography (MEG) to detect brain dysfunction in mild traumatic brain
      injured (MTBI) subjects. CONCLUSIONS: The following conclusions are offered: (1)
      standard clinical EEG is not useful; however, newer analytical procedures may be
      proven valuable; (2) consistent with current theory of MTBI, cognitive ERPs seem
      to be more sensitive to injury than EPs; (3) development of an assessment battery
      that may include EEG, EPs, ERPs, and neuropsychologic testing is advocated.

PMID- 11461661
TI  - Computer-assisted exercise systems in traumatic brain injury: cases and
      commentary.

PMID- 11461662
TI  - The development of monoclonal antibody therapy in leukemias.
AB  - Conventional cytotoxic management of leukemia has less than optimal results,
      while it is associated with life-threatening toxic effects due to lack of
      specificity for hematopoietic cells. Therefore, novel therapeutic strategies with
      monoclonal antibodies (MAbs) are being explored for delivering chemotherapy or
      radiation directly to malignant cells. Recently, anti-CD33 antibodies have been
      engineered to target malignant myeloid and immature normal cells and have been
      used to deliver cytotoxic agents or radiation to leukemic cells. 131I-labeled
      anti-CD45 antibodies are used in combination with conventional chemotherapy in
      leukemic patients receiving marrow transplantation. Additionally, the emergence
      of Rituximab (against CD20) and Campath-1H (against CD52) for chronic lymphocytic
      leukemia (CLL) has provided encouraging clinical results for the prognosis of
      this disease. In conclusion, there has been ongoing research indicating that the
      approach of patients with leukemia through the application of MAbs might be safer
      and more effective than current treatment. Considering the preliminary data, MAb
      therapy appears to be a new, promising weapon in the oncologist's armentarium.

PMID- 11461663
TI  - Detection of superficial zone protein in human and animal body fluids by cross
      species monoclonal antibodies specific to superficial zone protein.
AB  - In this report we describe the purification of human superficial zone protein
      (SZP), the generation of cross-species monoclonal antibodies (MAbs) and the
      detection of this protein in human and animal body fluids. Human SZPs, used as
      immunizing antigens, were purified either from culture media of human cartilage
      organ cultures or from human synovial fluids. The immunizing antigens were mixed
      with RIBI adjuvant in one of three forms: nonmodified SZP, superficial zone
      protein-keyhole limpet hemocyanin conjugate (SZP-KLH), or a mixture of
      superficial zone protein and hyaluronic acid (SZP-HA). A panel of MAbs including
      GW4.23, S6.79, S13.52, S13.233, and S17.109 were generated and characterized.
      Monoclonal antibody (MAb) S6.79, an IgG2b with K(D) 3.14 x 10(-9) M from SZP-KLH
      immunization, is of particular interest. It reacts strongly to a large molecular
      weight form of SZP in both enzyme-linked immunosorbent assay (ELISA) and Western
      blotting. It stains the most superficial layer of articular cartilage in
      immunohistochemistry, whereas the middle and deep zones of cartilage are not
      stained. When MAb S6.79 was applied to Western blots of human body fluids, a
      strong 345-kDa band was detected in samples of synovial fluid and weaker bands of
      similar size were detected in samples of plasma and serum. MAb S6.79 also showed
      cross-species immunoreactivity with SZP in samples of synovial fluids harvested
      from bovine, dog, guinea pig, and rabbit, as demonstrated by Western blotting and
      antibody absorption experiments. This cross-species MAb will be a useful tool in
      human and animal model studies for monitoring SZP levels and tissue distribution.
      It may help define the roles of SZP in normal articular joints and may be of
      diagnostic or prognostic value for the measurement of SZP in pathological
      conditions such as osteoarthritis, rheumatoid arthritis, and camptodactyly
      arthropathy-coxa vara-pericarditis.

PMID- 11461664
TI  - Monoclonal antibodies to Kaiso: a novel transcription factor and p120ctn-binding
      protein.
AB  - The POZ-zinc finger protein Kaiso belongs to a rapidly growing superfamily of
      BTB/POZ zinc finger transcription factors implicated in embryonic development and
      cancer. Kaiso interacts with the catenin p120(ctn), but the significance of the
      interaction remains unknown. Although p120(ctn) is normally found in association
      with E-cadherin at cell-cell junctions, it can translocate to the nucleus under
      certain circumstances. Thus, the p120(ctn)-Kaiso interaction may regulate
      transcriptional events, as has been described previously for the classical
      catenin, beta-catenin and the LEF1/TCF transcription factor. To facilitate
      further study of Kaiso and to determine the physiological relevance of its
      interaction with p120(ctn), we have generated and characterized a panel of five
      Kaiso-specific monoclonal antibodies (MAbs) that function in immunoblotting,
      immunoprecipitation, and immunofluorescence analyses.

PMID- 11461665
TI  - An antibody to p16INK4A recognizes a modified form of galectin-3.
AB  - Galectin-3 is a carbohydrate binding protein involved in multiple processes
      including cell-cycle regulation and apoptosis. The ability of galectin-3 to
      protect cells from apoptosis is dependent upon a region of the protein known as a
      BH-1 domain for its homology to the anti-apoptotic protein Bcl-2. Here, we show
      that a monoclonal antibody (MAb) to the human tumor suppressor protein p16INK4A
      recognizes a post-translationally modified form of human galectin-3. The modified
      form is detectable in only a subset of cell types expressing galectin-3,
      indicating that the modification is cell-type-specific. Although there is little
      amino acid sequence homology between p16INK4a and galectin-3, we show by epitope
      mapping that the modification directly affects the structure of galectin-3's BH-1
      domain. Elucidation of the nature of this modification might provide further
      insight into galectin-3 function.

PMID- 11461666
TI  - Generation and characterization of recombinant ScFv antibodies detecting Eimeria
      acervulina surface antigens.
AB  - In our previous attempt to generate monoclonal antibodies (MAbs) against coccidia
      parasites that more accurately reflect the natural avian humoral immune response,
      we produced two chicken B-cell hybridomas, 5D11 and 2-1. While both cell lines
      secreted antibodies reactive with sporozoites of Eimeria acervulina, they were
      produced in yields too low to conduct meaningful in vivo studies. To circumvent
      this problem, we produced four single chain variable fragment (scFv) antibodies
      from the V(H) and V(L) genes of hybridomas 5D11 and 2-1. The concentration of
      these recombinant antibodies expressed in E. coli and purified to homogeneity was
      5-6 mg/L. Three of the antibodies exhibited antigen binding specificity to
      Eimeria surface antigens equivalent to that of the native MAbs. Nucleotide
      sequence analysis of the V(L) genes from hybridomas 5D11 and 2-1 and genomic DNA
      revealed vestiges of gene conversion with V(lambda) pseudogenes. These
      recombinant scFv antibodies will prove useful for further characterization of
      natural Eimeria surface antigens as potential vaccine candidates.

PMID- 11461667
TI  - Preparation of monoclonal antibodies against human telomerase.
AB  - Telomerase, a ribonucleoprotein enzyme that extends telomeres of eukaryotic
      chromosomes, consists of the catalytic protein submit telomerase reverse
      transcriptase (TERT) and a telomerase RNA subunit. Nearly 85% of human tumors
      have tested positive for high telomerase activity. Telomerase activity is very
      low or not present in normal cells, whereas it is up-regulated in immortalized
      cells. Telomerase, partially purified from the breast tumor cell line MCF-7, was
      used to immunize Balb/C mice. Monoclonal antibodies (MAbs) were prepared by
      conventional hybridoma technology and screened by enzyme-linked immunoadsorbent
      assay (ELISA), followed by a polymerase chain reaction (PCR) based telomeric
      amplification repeat protocol (TRAP) assay to detect binding to or inhibition of
      telomerase activity. Reactive MAbs were found to be of IgM type by mu specific
      ELISA. Two MAbs were characterized, one that neutralizes telomerase activity in
      TRAP assay and the other non-neutralizing. In Western blotting, crude telomerase
      extract and HIV-1 virus lysate (control) were blotted on nitrocellulose membranes
      and the strips were treated with both MAbs and a nonrelated HIV polymerase
      specific MAb, also IgM type. A band of approx. 65-kDa was detected in extracts of
      293 cells with both the MAbs, but no reaction occurred with the HIV polymerase
      specific MAb used as control. Similarly, when HIV-1 virus lysate strips were
      treated with HIV polymerase-specific MAb, a 65-kDa band was detected and no band
      was observed with either of the hybridoma supernatants. These antibodies may be
      useful for studying regulatory mechanism of telomerase and inhibition of its
      activity in vitro and in vivo.

PMID- 11461668
TI  - Recombinant human interleukin-6 enhances the immunoglobulin secretion of a rabbit
      rabbit hybridoma.
AB  - The generation of stable rabbit-rabbit hybridomas is now possible by the recent
      development of a rabbit fusion partner. The ability to generate rabbit monoclonal
      antibodies (MAbs) can be advantageous because these rabbit immunoglobulins tend
      to exhibit higher affinity than murine MAbs. Furthermore, it has been observed
      that, in general, rabbits will elicit an immune response to antigens of limited
      immunogenicity in mice. Unfortunately, these rabbit-rabbit hybridomas secrete
      only 200 ng/mL to 5 microg/mL of immunoglobulin, which may limit larger scale
      production of rabbit antibodies. This study sought to determine if interleukin 6
      (IL-6), which has been reported to have proliferative and secretory stimulating
      effects on some murine hybridomas, had any effect on a rabbit cell line that
      secretes a monoclonal IgG specific for estradiol. The results demonstrated that
      recombinant human IL-6 had a dose-dependent enhancing effect on the IgG secretion
      of the rabbit-rabbit hybridoma. The enhancing effect was consistent when the
      cells were continuously passed in the presence of IL-6. However, IL-6 did not
      affect the growth of the hybridoma. In contrast, no discernible effect was
      accomplished with recombinant mouse IL-6. Furthermore, no basal IL-6 activity was
      detected in the rabbit hybridoma extracellular medium. The IL-6 enhancement
      effect observed in this study may help to increase the immunoglobulin yield of
      rabbit hybridomas and to assist in the understanding of the mechanism(s) behind
      the lowered secretion level.

PMID- 11461669
TI  - Generation and characterization of monoclonal antibodies to the neural crest.
AB  - The generation of monoclonal antibodies (MAbs) specific for quail neural crest
      may provide valuable tools for studying the differentiation of embryonic
      precursor cells. Unfortunately, relatively few antibodies are available because
      of the difficulty in obtaining sufficient cells for in vivo immunization
      strategies. We have overcome this problem by using intrasplenic immunization with
      formaldehyde-fixed cells harvested from neural crest cultures. In addition,
      booster injections of cultured whole-embryo cells were administered
      intraperitoneally. Following two fusions, a total of 18 hybridomas were generated
      with antibody reactivity to the cytoplasm of neural crest cells. Furthermore, 32
      were reactive against both somite (a noncrest mesodermal control) and crest
      cultures, whilst 15 were not reactive. Out of those hybridomas reactive with
      neural crest, six designated 160D, 164D, OE, 12E, 120E and 124E were further
      characterized. Interestingly MAb supernatants OE, 12E, 120E, and 124E exhibited
      reactivity against some but not all neural crest cells suggesting that they might
      recognise subpopulations. Immunoglobulin isotyping of supernatants revealed that
      4 (160D, 164D, OE, and 120E) were IgM and 2 (12E and 124E) were IgG(2b). On
      assessing their reactivity against human tissue sections, all six hybridoma
      supernatants cross-reacted with neuroendocrine cells within appendix, colon and
      rectum. These MAbs could provide novel reagents for the understanding of neural
      crest development.

PMID- 11461670
TI  - Method for rapidly preparing emulsion of antigen solution with adjuvant.

PMID- 11461674
TI  - An IL-2/Ig fusion protein influences CD4+ T lymphocytes in naive and simian
      immunodeficiency virus-infected Rhesus monkeys.
AB  - The T cell-stimulatory cytokine interleukin 2 (IL-2) is being evaluated as a
      therapeutic in the clinical settings of HIV infection and cancer. However, the
      clinical utility of IL-2 may be mitigated by its short in vivo half-life, toxic
      effects, and high production costs. We show here that an IL-2/Ig fusion protein
      possesses IL-2 immunostimulatory activity in vitro and a long in vivo half-life.
      IL-2/Ig treatment of healthy rhesus monkeys induced significant increases in
      CD4(+) T lymphocyte counts and expression of CD25 by these cells. Short courses
      of IL-2/Ig treatment of simian immunodeficiency virus (SIV)-infected rhesus
      monkeys in conjunction with antiretroviral drugs resulted in increased CD25
      expression on T lymphocytes, and transient increases in CD4(+) T lymphocyte
      counts. Plasma viremia did not increase in these treated animals. Treatment of
      healthy or SIV-infected rhesus monkeys with a plasmid encoding the IL-2/Ig
      protein did not affect CD4(+) T lymphocytes. These results demonstrate that IL
      2/Ig has potential utility as an immunostimulatory therapeutic.

PMID- 11461675
TI  - Improvement of HIV-specific immunity in HIV-infected twins treated with highly
      active antiretroviral therapy, interleukin 2, and syngeneic adoptively
      transferred cells.
AB  - Five HIV-seropositive twins were treated with HAART and given cycles of treatment
      consisting of adoptive cellular therapy from their HIV-seronegative identical
      twins followed by a 5-day course of intravenous IL-2. Changes in absolute and
      percent CD4(+) and CD8(+) cell count were monitored and compared with changes in
      these parameters occurring in seven age-, sex-, and disease stage-matched HIV
      infected patients treated with HAART alone. Increase in the magnitude and breadth
      of HIV-specific immune responses was monitored in three twin subjects who
      received multiple treatment cycles. Absolute and percent CD4(+) cell counts rose
      dramatically and to significantly higher levels in the recipient twins than in
      control subjects treated with HAART only. The subjects who received multiple
      cycles of treatment developed new and increased levels of HIV-specific activated
      and memory cytotoxic T lymphocyte responses, and interferon gamma-secreting
      effector cells. Treatment consisting of HAART, adoptive cellular therapy, and IL
      2 was superior to treatment with HAART alone for improving absolute and percent
      CD4(+) cell counts and inducing new, or increasing the magnitude of, HIV-specific
      immune responses in HIV infected patients.

PMID- 11461676
TI  - Virologic and immunologic determinants of heterosexual transmission of human
      immunodeficiency virus type 1 in Africa.
AB  - More than 80% of the world's HIV-infected adults live in sub-Saharan Africa,
      where heterosexual transmission is the predominant mode of spread. The virologic
      and immunologic correlates of female-to-male (FTM) and male-to-female (MTF)
      transmission are not well understood. A total of 1022 heterosexual couples with
      discordant HIV-1 serology results (one partner HIV infected, the other HIV
      uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored
      at 3-month intervals. A nested case-control design was used to compare 109
      transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA
      (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was
      significantly higher in transmitters than nontransmitters (123,507 vs. 51,310
      copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the
      risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL > or =
      100,000 copies/ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000
      copies/ml compared with the reference group of <10,000 copies/ml. Corresponding
      RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both
      bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml
      compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The
      transmission rate within couples was 7.7/100 person-years and did not differ from
      FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude
      that the association between increasing plasma viral load was strong for female
      to male transmission, but was only weakly predictive of male to female
      transmission in Zambian heterosexual couples. FTM and MTF transmission rates were
      similar. These data suggest gender-specific differences in the biology of
      heterosexual transmission.

PMID- 11461677
TI  - Low conservation of functional domains of HIV type 1 vif and vpr genes in
      infected mothers correlates with lack of vertical transmission.
AB  - Human immunodeficiency virus type 1 (HIV-1) vif and vpr sequences were analyzed
      from four nontransmitting mothers (infected mothers who failed to transmit HIV-1
      to their infants mainly in the absence of anti-retroviral therapy), including a
      mother with multiple deliveries, and compared with the vif and vpr sequences of
      five and six previously analyzed transmitting mothers, respectively. In contrast
      to a high functional conservation of vif and vpr genes in transmitting mother
      isolates, we found that there was a low degree of conservation of functional
      domains of these genes in nontransmitting (NT) mother isolates. For vif
      sequences, NT-2 contained stop codons and no initiation codons, whereas NT-1
      sequences carried a substitution of a highly conserved tyrosine to histidine at
      position 30. In addition, NT-3 and NT-4 sequences contained additional
      substitutions, including asparagine at position 22, lysine at position 77 and
      histidine at position 110, that were absent in transmitting mother and consensus
      subtype B sequences. Similarly, the vpr sequences of NT-2 contained stop codons
      and no initiation codons, NT-4 contained a substitution of serine in place of
      alanine at position 30, some NT-1 sequences substituted arginine in place of
      glycine at position 75, and NT-3 sequences presented a deletion in the C terminus
      that was absent in transmitting mother and consensus subtype B sequences and is
      essential for Vpr function. Furthermore, vif and vpr sequences of nontransmitting
      mothers were less heterogeneous compared with transmitting mother sequences. In
      conclusion, a low degree of conservation of functional domains and heterogeneity
      of HIV-1 vif and vpr genes in these infected mothers correlates with lack of
      vertical transmission.

PMID- 11461678
TI  - HIV type 1 chemokine receptor usage in mother-to-child transmission.
AB  - To investigate the role of the HIV-1 phenotype in mother-to-child HIV-1
      transmission, we evaluated coreceptor usage and replication kinetics in chemokine
      receptor-expressing U87MG.CD4 cells of primary isolates from 32 HIV-1-infected
      mothers of Italian origin, none under preventive antiretroviral therapy, and from
      their infected infants. Five of 15 mothers of infected children and 2 of 17
      mothers of uninfected children harbored viruses able to use CXCR4 as coreceptor.
      However, all isolates used CCR5, alone or in association with CXCR4. The
      replicative capacity in coreceptor-expressing cells of the viral isolates did not
      differ between the two groups of mothers. All mothers with an R5 virus
      transmitted a virus with the same coreceptor usage, whereas those four with a
      multitropic virus transmitted such a virus in one case. Although the presence of
      a mixed viral population was documented in the mothers, we did not observe
      transmission solely of X4 viruses. Interestingly, the only child infected with a
      multitropic virus carried a defective CCR5 allele. Analysis of the env V3 region
      of the provirus from this child revealed infection with multiple viral variants
      with a predominance of R5-type over X4-type sequences. These findings show that
      CCR5 usage of a viral isolate is not a discriminating risk factor for vertical
      transmission. Furthermore, X4 viruses can be transmitted to the newborn, although
      less frequently. In particular, we document the transmission of multiple viral
      variants with different coreceptor usage in a Delta32 CCR5 heterozygous child,
      and demonstrate that the heterozygous genotype per se does not contribute to the
      restriction of R5-type virus spread.

PMID- 11461679
TI  - Synthetic peptide strategy for the detection of and discrimination among highly
      divergent primate lentiviruses.
AB  - We developed a simple, rapid, inexpensive, and highly sensitive and specific
      strategy for the detection and lineage differentiation of primate lentiviruses
      (PIV-ELISA). It is based on the use of two indirect ELISA methods using synthetic
      peptides mapping the gp41/36 region (detection component) and the V3 region
      (differentiation component) of four lentivirus lineages, namely SIVcpz/HIV-1
      (groups M, O, N, and SIVcpz-gab), SIVmnd, SIVagm, and SIVsm/SIVmac/HIV-2. This
      strategy was evaluated with panels of sera originating from both humans and
      nonhuman primates. The human reference panel consisted of 144 HIV Western blot
      (WB)-positive sera in which the corresponding virus had been genotyped (HIV-1: 72
      group M, 28 group O, and 6 group N; HIV-2: 21 subtype A and 10 subtype B; and 7
      HIV-1+2) and 105 HIV WB-negative samples. The nonhuman primate reference panel
      consisted of 24 sera from monkeys infected by viruses belonging to the four
      lineages included in the PIV-ELISA strategy (5 chimpanzees, 5 macaques, 8
      mandrills, and 6 vervets) and 42 samples from seronegative animals. Additional
      field evaluation panels consisted of 815 human sera from Gabon, Cameroon, and
      France and 537 samples from 25 nonhuman primate species. All the samples from the
      two reference panels were correctly detected and discriminated by PIV-ELISA. In
      the human field evaluation panel, the gp41/36 component correctly identified all
      the test samples, with 98% specificity. The V3 component discriminated 206 HIV-1
      group M, 98 group O, 12 group M+O, and 128 HIV-2 sera. In the primate field
      evaluation panel, both gp41/36 and V3 detected and discriminated all the WB
      positive samples originating from monkeys infected with SIVcpz, SIVagm-ver,
      SIVmnd-1, SIVmnd-2, SIVdrl, or SIVsun. These results were confirmed by genotyping
      in every case. Four SIV-infected red-capped mangabeys (confirmed by PCR) were
      correctly identified by gp41/36, but only two reacted with the V3 peptides in the
      absence of a specific SIVrcm V3 peptide. Addition of a V3 SIVrcm peptide
      discriminated all the SIVrcm-positive samples. Fourteen Papio papio samples were
      positive for SIVsm gp 36 and by WB, but negative by PCR, whereas three Papio
      cynocephalus samples were positive by gp41/36 but indeterminate by WB and
      negative by PCR. This combined ELISA system is thus highly sensitive and specific
      for antibodies directed against HIV and SIV. In addition, the V3-based serotyping
      results always agreed with genotyping results. This method should prove useful
      for studies of lentivirus prevalence and diversity in human and nonhuman
      primates, and may also have the potential to detect previously undescribed SIVs.

PMID- 11461680
TI  - Human retrovirus type 5 sequences in non-Hodgkin's lymphoma of T cell origin.
AB  - DNA of a recently described fifth exogenous retrovirus (HRV-5) has been found in
      blood samples from patients with autoimmune diseases and lymphoma. We analyzed
      HRV-5 sequence in DNA extracted from whole blood of 17 patients with T cell non
      Hodgkin's lymphoma (NHL) and 186 patients with hematological malignancies other
      than NHL, using a sensitive PCR technique. While all samples of patients with
      hematological malignancies other than NHL were negative, 2 of the 17 patients
      with T cell NHL were HRV-5 DNA positive. Both HRV-5-positive patients had T cell
      NHL of high-grade malignancy (stage IV) and diffuse distribution of the lymphoma,
      including infiltration of bone marrow or lung and pleura. The difference in HRV-5
      DNA detection frequency between NHL and control groups is significant (p value of
      0.0004 judged by the Fisher exact test). These data, together with our previous
      finding of HRV-5 DNA in three B cell NHL cases, are compatible with an
      association between HRV-5 and NHL, of both T cell and B cell origin.

PMID- 11461681
TI  - Concordant utilization of macrophage entry coreceptors by related variants within
      an HIV type 1 primary isolate viral swarm.
AB  - There is considerable diversity among HIV-1 strains in terms of their ability to
      use entry coreceptors on macrophages, especially CXCR4, but it is not known
      whether virus-specific differences exist among related members of a viral swarm.
      Defining how entry coreceptors on primary target cells are utilized by the
      spectrum of HIV-1 variants that emerge in vivo is important for understanding the
      relationship between coreceptor selectivity and pathogenesis. HIV-1 89.6(PI) is a
      dual-tropic primary isolate, and the prototype 89.6-cloned R5X4 Env uses both
      CXCR4 and CCR5 on macrophages. We generated a panel of env clones from the
      89.6(PI) quasispecies and found a mixture of R5, R5X4, and X4 variants on the
      basis of fusion and infection of coreceptor-transfected cell lines. Here we
      address the use of macrophage coreceptors by these related Envs by analyzing
      fusion and infection of primary monocyte-derived macrophages mediated
      specifically through each coreceptor. All R5X4 Envs utilized both CXCR4 and CCR5
      on macrophages, while R5 variants used CCR5 only. One variant characterized in
      cell lines as X4 used both CXCR4 and CCR5 on macrophages. No Env variant fused
      with macrophages through alternative coreceptor pathways. Thus, there was
      heterogeneity in coreceptor use among the related Env variants, but use of each
      coreceptor specifically in macrophages was consistent among members of the viral
      swarm. Coreceptor use in transfected cells generally predicted use in primary
      macrophages, although for some Envs macrophages may be a more sensitive indicator
      of CCR5 use than transfected cell lines.

PMID- 11461682
TI  - HIV type 1 Tat protein is a survival factor for Kaposi's sarcoma and endothelial
      cells.
AB  - The HIV-1 Tat protein has been directly implicated in the pathogenesis of AIDS
      related Kaposi's sarcoma (KS); however, its effects on KS spindle-shaped and
      endothelial cell apoptosis are largely unexplored. Since susceptibility to
      apoptosis is relevant for tumor development and response to therapy, we
      investigated the effects of Tat on KS and endothelial cell survival from
      apoptosis. The effect of Tat was evaluated in three KS cell lines (KS-imm, KS-C1,
      and KS-L3) exposed to the chemotherapy agent vincristine, currently used for the
      treatment of this tumor, and in human umbilical vein-derived endothelial cells
      (HUVECs) induced to undergo apoptosis by serum withdrawal. Apoptosis was assessed
      by enzymatic assays, microscopic examination of chromatin and cytoskeleton,
      evaluation of plasma membrane integrity and subdiploid DNA content, TUNEL assays,
      and measurement of caspase-3 activity. Tat, in a dose-dependent manner, protected
      the three KS cell lines and HUVECs from apoptosis induced by vincristine or serum
      starvation, respectively. This effect appeared to be independent of modulation of
      Fas, Bcl-2, or Bax expression. In contrast, Tat upregulated Bcl-X(L) expression
      and induced a relevant decrease in caspase-3 activity in vincristine-treated KS
      cells. Taken together, these results suggest that the HIV-1 Tat protein may
      factor KS development and progression by sustaining endothelial and transformed
      cell survival.

PMID- 11461683
TI  - Percentage of CD3+CD4-CD8-gammadeltaTCR- T cells is increased HIV disease.
AB  - HIV patients given highly active antiretroviral therapy (HAART) experience a
      rapid rise in alphabetaT cell numbers, but changes in gammadeltaT cell
      populations have not been described. Here we investigate the effects of immune
      reconstitution and immune restoration diseases (IRDs) on expression of a pan
      gammadeltaT cell receptor (TCR) marker on double-negative (CD3(+)CD4(-)CD8(-)) T
      cells and T cells expressing CD4 or CD8. IRDs are inflammatory disorders
      associated with preexisting infections in patients who have achieved immune
      reconstitution after HAART. Proportions of CD3(+)CD4(-)CD8(-) T cells and total
      gammadeltaT cells were not affected by CD4(+) T cell counts, HAART, or a history
      of IRD, but levels of CD4(-)CD8(-)gammadeltaTCR(-) T cells were higher in
      patients with <15% CD4(+) T cells.

PMID- 11461684
TI  - Identification and comparison of eleven rhesus macaque chemokine receptors.
AB  - Both simian and human immunodeficiency viruses (SIV and HIV) utilize chemokine
      receptors, with or without CD4, as portals for entry into susceptible cells. In
      this report, we present the cloning and comparison of 11 rhesus macaque chemokine
      receptors and receptor-like proteins (CCR1, CCR2b, CCR3, CCR5, CCR8, CXCR4,
      STRL33, GPR1, GPR15, APJ, and CRAM-A/B), the human counterparts of which have
      been previously shown to be utilized by SIV for entry.

PMID- 11461685
TI  - Isolation and phylogenetic analysis of HERV-K long terminal repeat cDNA in cancer
      cells.
AB  - Long terminal repeat (LTR) elements of human endogenous retrovirus (HERV-K) may
      have contributed to disease-associated structural change or genetic variation in
      the human genome. The LTR elements have been found to be coexpressed with
      sequences of closely located genes. We identified seven HERV-K LTR elements from
      mRNA of human cancer cells (HepG2, MCF7, and SiHa), using the RT-PCR approach.
      Four of them are closely related to the human-specific HERV-K LTR elements with a
      high degree of sequence homology in a neighbor-joining phylogenetic tree. The
      data suggest that recently proliferated HERV-K LTR elements are expressed
      actively in various cancer cells. These HERV-K LTR elements deserve further
      investigation as potential leads in the treatment of human cancer.

PMID- 11461687
TI  - Conditions enabling the evolution of inter-agent signaling in an artificial
      world.
AB  - In the research described here we extend past computational investigations of
      animal signaling by studying an artificial world in which a population of
      initially noncommunicating agents evolves to communicate about food sources and
      predators. Signaling in this world can be either beneficial (e.g., warning of
      nearby predators) or costly (e.g., attracting predators or competing agents). Our
      goals were twofold: to examine systematically environmental conditions under
      which grounded signaling does or does not evolve, and to determine how variations
      in assumptions made about the evolutionary process influence the outcome. Among
      other things, we found that agents warning of nearby predators were a common
      occurrence whenever predators had a significant impact on survival and signaling
      could interfere with predator success. The setting most likely to lead to food
      signaling was found to be difficult-to-locate food sources that each have
      relatively large amounts of food. Deviations from the selection methods typically
      used in traditional genetic algorithms were also found to have a substantial
      impact on whether communication evolved. For example, constraining parent
      selection and child placement to physically neighboring areas facilitated
      evolution of signaling in general, whereas basing parent selection upon survival
      alone rather than survival plus fitness measured as success in food acquisition
      was more conducive to the emergence of predator alarm signals. We examine the
      mechanisms underlying these and other results, relate them to existing
      experimental data about animal signaling, and discuss their implications for
      artificial life research involving evolution of communication.

PMID- 11461688
TI  - Symbiogenesis in learning classifier systems.
AB  - Symbiosis is the phenomenon in which organisms of different species live together
      in close association, resulting in a raised level of fitness for one or more of
      the organisms. Symbiogenesis is the name given to the process by which symbiotic
      partners combine and unify, that is, become genetically linked, giving rise to
      new morphologies and physiologies evolutionarily more advanced than their
      constituents. The importance of this process in the evolution of complexity is
      now well established. Learning classifier systems are a machine learning
      technique that uses both evolutionary computing techniques and reinforcement
      learning to develop a population of cooperative rules to solve a given task. In
      this article we examine the use of symbiogenesis within the classifier system
      rule base to improve their performance. Results show that incorporating simple
      rule linkage does not give any benefits. The concept of (temporal) encapsulation
      is then added to the symbiotic rules and shown to improve performance in
      ambiguous/non-Markov environments.

PMID- 11461689
TI  - Digital life behavior in the Amoeba world.
AB  - Amoeba is a computer model designed to facilitate the study of the origin and
      evolution of digital life. Specifically, an initially disordered system,
      consisting of random sequences of machine instructions, self-organizes into an
      ordered system containing self-replicating programs. The current version of
      Amoeba broadens the original system's capability by using a basis set of 32
      machine instructions that is computationally universal. In addition, Amoeba uses
      a set of 64 address labels, each of which is randomly assigned to a machine
      instruction each time a sequence is randomly created. This eliminates the
      constraint that occurs when the complements of predefined codons are used for
      addressing. A more open-ended system results because programs can now form
      subroutines that are arranged in an arbitrary manner.

PMID- 11461690
TI  - Recent developments in the evolution of morphologies and controllers for
      physically simulated creatures.
AB  - Karl Sims' work on evolving body shapes and controllers for three-dimensional,
      physically simulated creatures generated wide interest on its publication in
      1994. The purpose of this article is threefold: (a) to highlight a spate of
      recent work by a number of researchers in replicating, and in some cases
      extending, Sims' results using standard PCs (Sims' original work was done on a
      Connection Machine CM-5 parallel computer). In particular, a re-implementation of
      Sims' work by the authors will be described and discussed; (b) to illustrate how
      off-the-shelf physics engines can be used in this sort of work, and also to
      highlight some deficiencies of these engines and pitfalls when using them; and
      (c) to indicate how these recent studies stand in respect to Sims' original work.

PMID- 11461694
TI  - Endocytosis and signaling. an inseparable partnership.

PMID- 11461695
TI  - State of the arg: protein methylation at arginine comes of age.

PMID- 11461696
TI  - Accounting for specificity in receptor tyrosine kinase signaling.

PMID- 11461697
TI  - Polar explorers: membrane proteins that determine division site placement.

PMID- 11461698
TI  - The organizer and beyond.

PMID- 11461699
TI  - Genes and mechanisms related to RNA interference regulate expression of the small
      temporal RNAs that control C. elegans developmental timing.
AB  - RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA and
      involves the generation of 21 to 26 nt RNA segments that guide mRNA destruction.
      In Caenorhabditis elegans, lin-4 and let-7 encode small temporal RNAs (stRNAs) of
      22 nt that regulate stage-specific development. Here we show that inactivation of
      genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and
      two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar
      to lin-4 and let-7 mutations. Further we show that dcr-1, alg-1, and alg-2 are
      necessary for the maturation and activity of the lin-4 and let-7 stRNAs. Our
      findings suggest that a common processing machinery generates guide RNAs that
      mediate both RNAi and endogenous gene regulation.

PMID- 11461700
TI  - In vivo analysis of Drosophila bicoid mRNA localization reveals a novel
      microtubule-dependent axis specification pathway.
AB  - Drosophila bicoid mRNA is synthesized in the nurse cells and transported to the
      oocyte where microtubules and Exuperantia protein mediate localization to the
      anterior pole. Fluorescent bicoid mRNA injected into the oocyte displays nonpolar
      microtubule-dependent transport to the closest cortical surface, and the oocyte
      microtubule cytoskeleton lacks clear axial asymmetry. Nonetheless, bicoid mRNA
      injected into the nurse cell cytoplasm, withdrawn, and injected into a second
      oocyte shows microtubule-dependent transport to the anterior cortex. Nurse cells
      require microtubules and Exuperantia to support anterior transport of bicoid
      mRNA, and microtubules are required for bicoid mRNA-Exuperantia particle
      coassembly. We propose that microtubule-dependent Exuperantia-bicoid mRNA complex
      formation in the nurse cell cytoplasm allows anterior-specific transport on a
      grossly nonpolar oocyte microtubule network.

PMID- 11461701
TI  - Differential timing and control of noncrossover and crossover recombination
      during meiosis.
AB  - Unitary models of meiotic recombination postulate that a central intermediate
      containing Holliday junctions is resolved to generate either noncrossover or
      crossover recombinants, both of which contain heteroduplex DNA. Contrary to this
      expectation, we find that during meiosis in Saccharomyces cerevisiae,
      noncrossover heteroduplex products are formed at the same time as Holliday
      junction intermediates. Crossovers appear later, when these intermediates are
      resolved. Furthermore, noncrossover and crossover recombination are regulated
      differently. ndt80 mutants arrest in meiosis with unresolved Holliday junction
      intermediates and very few crossovers, while noncrossover heteroduplex products
      are formed at normal levels and with normal timing. These results suggest that
      crossovers are formed by resolution of Holliday junction intermediates, while
      most noncrossover recombinants arise by a different, earlier pathway.

PMID- 11461702
TI  - The single-end invasion: an asymmetric intermediate at the double-strand break to
      double-holliday junction transition of meiotic recombination.
AB  - We identify a novel meiotic recombination intermediate, the single-end invasion
      (SEI), which occurs during the transition from double-strand breaks (DSBs) to
      double-Holliday junction (dHJs). SEIs are products of strand exchange between one
      DSB end and its homolog. The structural asymmetry of SEIs indicates that the two
      ends of a DSB interact with the homolog in temporal succession, via structurally
      (and thus biochemically) distinct processes. SEIs arise surprisingly late in
      prophase, concomitant with synaptonemal complex (SC) formation. These and other
      data imply that SEIs are preceded by nascent DSB-partner intermediates, which
      then undergo selective differentiation into crossover and noncrossover types,
      with SC formation and strand exchange as downstream consequences. Late occurrence
      of strand exchange provides opportunity to reverse recombinational fate even
      after homologs are coaligned and/or synapsed. This feature can explain crossover
      suppression between homeologous and structurally heterozygous chromosomes.

PMID- 11461703
TI  - Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription
      complex.
AB  - The X-ray structure of a ternary complex of Negative Cofactor 2 (NC2), the TATA
      box binding protein (TBP), and DNA has been determined at 2.6 A resolution. The N
      termini of NC2 alpha and beta resemble histones H2A and H2B, respectively, and
      form a heterodimer that binds to the bent DNA double helix on the underside of
      the preformed TBP-DNA complex via electrostatic interactions. NC2beta contributes
      to inhibition of TATA-dependent transcription through interactions of its C
      terminal alpha helix with a conserved hydrophobic feature on the upper surface of
      TBP, which in turn positions the penultimate alpha helix of NC2beta to block
      recognition of the TBP-DNA complex by transcription factor IIB. Further
      regulatory implications of the NC2 heterodimer structure are discussed.

PMID- 11461704
TI  - Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic
      checkpoint.
AB  - The mitotic checkpoint acts to inhibit entry into anaphase until all chromosomes
      have successfully attached to spindle microtubules. Unattached kinetochores are
      believed to release an activated form of Mad2 that inhibits APC/C-dependent
      ubiquitination and subsequent proteolysis of components needed for anaphase
      onset. Using Xenopus egg extracts, a vertebrate homolog of yeast Mps1p is shown
      here to be a kinetochore-associated kinase, whose activity is necessary to
      establish and maintain the checkpoint. Since high levels of Mad2 overcome
      checkpoint loss in Mps1-depleted extracts, Mps1 acts upstream of Mad2-mediated
      inhibition of APC/C. Mps1 is essential for the checkpoint because it is required
      for recruitment and retention of active CENP-E at kinetochores, which in turn is
      necessary for kinetochore association of Mad1 and Mad2.

PMID- 11461705
TI  - The mouse Mps1p-like kinase regulates centrosome duplication.
AB  - The yeast Mps1p protein kinase acts in centrosome duplication and the spindle
      assembly checkpoint. We demonstrate here that a mouse Mps1p ortholog (esk, which
      we designate mMps1p) regulates centrosome duplication. Endogenous mMps1p and
      overexpressed GFP-mMps1p localize to centrosomes and kinetochores in mouse cells.
      Overexpression of GFP-mMps1p causes reduplication of centrosomes during S phase
      arrest. In contrast, a kinase-deficient mutant blocks centrosome duplication
      altogether. Control of centrosome duplication by mMps1p requires a known
      regulator of the process, Cdk2. Inhibition of Cdk2 prevents centrosome
      reduplication and destabilizes mMps1p, causing its subsequent loss from
      centrosomes, suggesting that Cdk2 promotes mMps1p's centrosome duplication
      function by regulating its stability during S phase. Thus, mMps1p, an in vitro
      Cdk2 substrate, regulates centrosome duplication jointly with Cdk2.

PMID- 11461706
TI  - Transgenic expression of syndecan-1 uncovers a physiological control of feeding
      behavior by syndecan-3.
AB  - Transgenic expression in the hypothalamus of syndecan-1, a cell surface heparan
      sulfate proteoglycan (HSPG) and modulator of ligand-receptor encounters, produces
      mice with hyperphagia and maturity-onset obesity resembling mice with reduced
      action of alpha melanocyte stimulating hormone (alphaMSH). Via their HS chains,
      syndecans potentiate the action of agouti-related protein and agouti signaling
      protein, endogenous inhibitors of alphaMSH. In wild-type mice, syndecan-3, the
      predominantly neural syndecan, is expressed in hypothalamic regions that control
      energy balance. Food deprivation increases hypothalamic syndecan-3 levels several
      fold. Syndecan-3 null mice, otherwise apparently normal, respond to food
      deprivation with markedly reduced reflex hyperphagia. We propose that oscillation
      of hypothalamic syndecan-3 levels physiologically modulates feeding behavior.

PMID- 11461707
TI  - Folate receptor-alpha is a cofactor for cellular entry by Marburg and Ebola
      viruses.
AB  - Human infections by Marburg (MBG) and Ebola (EBO) viruses result in lethal
      hemorrhagic fever. To identify cellular entry factors employed by MBG virus,
      noninfectible cells transduced with an expression library were challenged with a
      selectable pseudotype virus packaged by MBG glycoproteins (GP). A cDNA encoding
      the folate receptor-alpha (FR-alpha) was recovered from cells exhibiting
      reconstitution of viral entry. A FR-alpha cDNA was recovered in a similar
      strategy employing EBO pseudotypes. FR-alpha expression in Jurkat cells
      facilitated MBG or EBO entry, and FR-blocking reagents inhibited infection by MBG
      or EBO. Finally, FR-alpha bound cells expressing MBG or EBO GP and mediated
      syncytia formation triggered by MBG GP. Thus, FR-alpha is a significant cofactor
      for cellular entry for MBG and EBO viruses.

PMID- 11461709
TI  - Corticosteroids and cognition.
AB  - The brain is a major target organ for corticosteroids. It has been observed that
      excessive circulatory levels of endogenous and exogenous corticosteroids are
      frequently associated with cognitive impairment in a wide variety of clinical
      disease states. Cognition and low levels of corticosteroids have been less well
      studied. In this paper we review the literature on glucocorticosteroid effects on
      cognition and delineate specific functions that appear to be causally affected.
      We draw a possible connection to specific areas of brain perturbation, including
      the hippocampus and frontal lobe regions. The possibility that cognitive
      dysfunction caused by glucocorticoids can be pharmacologically managed is
      introduced.

PMID- 11461710
TI  - Differential analysis of behavior and diazepam-induced alterations in C57BL/6N
      and BALB/c mice using the modified hole board test.
AB  - A variety of test procedures are used in preclinical research on behavioral
      pharmacology and to dissociate behavioral differences or pharmacologically
      induced behavioral alterations several independent tests are usually performed.
      In the present study we introduce a modified hole board procedure for mice which
      allows us to investigate a variety of behavioral parameters such as anxiety, risk
      assessment, exploration, locomotion, food-intake inhibition, novelty seeking, and
      arousal by using only one test. The modified hole board was established by
      investigating the behavior of two inbred mouse strains, C57BL/6 and BALB.
      Significant differences in terms of locomotor activity, general exploration, and
      other parameters were found. Moreover, strain-specific exploration strategies
      could be detected in the modified hole board. Further, the test was validated by
      investigating the effects of diazepam as standard anxiolytic on the behavior in
      both mouse strains. Acute administration of diazepam (1 and 3 mg/kg) induced
      strong sedative effects in a dose-dependent manner in C57BL/6 mice. In BALB mice,
      the lower dosage of diazepam showed an activating and anxiolytic action while the
      3 mg dosage revealed a slight sedative but still anxiolytic effect in these
      animals. Taken together, the results demonstrate that the modified hole board
      enables to differentially investigate behavioral phenotypes and also
      pharmacologically-induced behavioral alterations in mice. Therefore, this new
      strategy allows to reduce the number of experimental animals and the time needed,
      thus, representing an effective screening-tool for behavioral investigations.

PMID- 11461711
TI  - Delta sleep ratio as a predictor of sleep deprivation response in major
      depression.
AB  - The fast but short-lasting improvement of depressive symptoms by sleep
      deprivation (SD) in about 60% of patients with a major depressive disorder is
      well established, but the mechanisms of action are still not clear. Recent
      studies suggest that changes in non rapid eye movement (NREM) sleep, especially
      in slow wave activity (SWA), could be associated with the therapeutic outcome of
      SD. In the current study, spectral analysis of NREM sleep EEG directly prior to
      SD was performed to determine if automatically derived sleep parameters predict
      SD response. Sixteen pair matched and drug free patients with a major depressive
      disorder, 8 SD responders and 8 non-responders (response criterion: 50% reduction
      on the 6-item HAMD score), were included. Average EEG spectral power was
      calculated for the whole night before SD and for single NREM episodes. While
      whole-night averages of spectral power did not differ significantly between
      subgroups, SD responders showed a steady decrease of SWA across successive NREM
      episodes, whereas in non-responders an increase from the first to the second
      episode was observed. The different distribution of SWA was significantly
      expressed in the delta sleep ratio (quotient of SWA in the first to the second
      NREM episode). In conclusion, a high delta sleep ratio is a positive predictor
      for SD response. Referred to psycho- and pharmacotherapeutic results it is
      hypothesized that low and high values of the delta sleep ratio characterize
      subgroups of depressed patients with different neurobiological alterations, which
      could be relevant for further scientific and therapeutic approaches.

PMID- 11461712
TI  - The first-night effect may last more than one night.
AB  - The first-night effect in sleep polysomnographic studies is usually considered to
      last for one night. However, a few observations have indicated that variables
      associated to rapid eye movement sleep take longer to stabilize. Notwithstanding,
      current opinion holds that second nights of recording can be used without
      restriction for research and clinical purposes. The goal of this study was to
      describe the dynamics of habituation to polysomnography in optimal conditions.
      Twenty-six young, carefully screened, healthy subjects were recorded in their
      home for four consecutive full polysomnographies. Repeated measures ANOVA were
      applied. Between the two first nights, while there were no differences in sleep
      duration in non-rapid eye movement sleep, marked modifications in corresponding
      spectral power were observed. The dynamics of adaptation of rapid eye movement
      sleep appeared to be a process extending up to the fourth night. Similar dynamics
      in NREMS and REMS homeostasis have been observed in sleep deprivation studies,
      and it appears that the same mechanisms may be responsible for the FNE. The
      longer habituation process of REMS in particular has important implications for
      sleep research in psychiatry.

PMID- 11461713
TI  - Serotonin 2A receptor gene polymorphism is not associated with completed suicide.
AB  - Several lines of evidence indicate that a serotonergic dysfunction is involved in
      the biological susceptibility to suicide. Recently, the A-1438G polymorphism of
      the serotonin 2A (5-HT2A) receptor gene has been suggested to be associated with
      suicide, but the results are inconsistent. We examined whether the A-1438G
      polymorphism of the 5-HT2A receptor gene was associated with suicide itself using
      151 Japanese completed suicides. No significant difference in genotype
      distribution or allele frequencies of the polymorphism was found between the
      completed suicides and the comparison group. We conclude that the A-1438G
      polymorphism of the 5-HT2A receptor gene is not likely to have a major effect on
      the biological susceptibility of suicide.

PMID- 11461714
TI  - Accounting for covariate measurement error in a Cox model analysis of recurrence
      of depression.
AB  - When a covariate measured with error is used as a predictor in a survival
      analysis using the Cox model, the parameter estimate is usually biased. In
      clinical research, covariates measured without error such as treatment procedure
      or sex are often used in conjunction with a covariate measured with error. In a
      randomized clinical trial of two types of treatments, we account for the
      measurement error in the covariate, log-transformed total rapid eye movement
      (REM) activity counts, in a Cox model analysis of the time to recurrence of major
      depression in an elderly population. Regression calibration and two variants of a
      likelihood-based approach are used to account for measurement error. The
      likelihood-based approach is extended to account for the correlation between
      replicate measures of the covariate. Using the replicate data decreases the
      standard error of the parameter estimate for log(total REM) counts while
      maintaining the bias reduction of the estimate. We conclude that covariate
      measurement error and the correlation between replicates can affect results in a
      Cox model analysis and should be accounted for. In the depression data, these
      methods render comparable results that have less bias than the results when
      measurement error is ignored.

PMID- 11461715
TI  - Treatment with atypical antipsychotics: new indications and new populations.
AB  - Atypical antipsychotics have revolutionized the treatment of schizophrenia,
      becoming the treatment of choice for patients not only during their first
      episode, but also throughout their life course. Of note, as of 1999 more than 70%
      of prescriptions for these drugs are being prescribed for conditions other than
      schizophrenia, such as bipolar disorder and geriatric agitation. While there have
      been very few controlled trials that have established the efficacy of the
      atypical antipsychotics for these "off-label" uses, there have been a large
      number of open trials and case reports. The few controlled trials suggest that
      the atypical antipsychotics may be useful for affective disorders (both mania and
      depression), geriatric conditions such as senile dementia and aggression, as well
      as a variety of other disorders. Atypical agents may be particularly helpful for
      elderly, child, or adolescent patients who are especially susceptible to the side
      effects of medications and whose risk of tardive dyskinesia is high but further
      controlled studies are necessary.

PMID- 11461716
TI  - Evaluation of the offer of physical activity for the elderly in a region of
      France.
AB  - The aim of this study was an evaluation of the possibilities of physical activity
      for the elderly in a region of France where 24% of the population is over 65
      years old. It stressed the very poor level of physical activity in the community
      as well as in nursing homes. This situation is linked to a combination of
      factors: lack of interest, insufficient information and financial constraints.
      The 5-year plan we are developing in this region aims at the development of the
      practice of physical activity, to maintain as long as possible the autonomy and
      the quality of life of this growing elderly population.

PMID- 11461717
TI  - Plasma levels of vitamin E in Parkinson's disease.
AB  - Oxidative stress has been implicated as a major contributor to selective neuronal
      death in Parkinson's disease (PD). Vitamin E is an antioxidant that may protect
      the brain from free radical-induced oxidative damage. It is, therefore,
      reasonable to hypothesize that low levels of vitamin E concentrations may
      increase the risk of developing PD. To elucidate the possible role of vitamin E
      in the pathogenesis of PD, we assessed the plasma levels of vitamin E, measured
      by high-performance liquid chromatography (HPLC), in 54 patients with PD. Vitamin
      E concentrations were also assessed in 93 age and sex matched normal individuals.
      The mean plasma levels of vitamin E did not differ significantly between these
      two groups (22.5+/-8.15 &mgr;mol/l for PD patients and 21.0+/-7.9 &mgr;mol/l for
      controls). The results of our study suggest that plasma vitamin E concentrations
      do not play a major role in the pathogenesis of PD.

PMID- 11461718
TI  - Cyclooxygenase and Alzheimer's disease: implications for preventive initiatives
      to slow the progression of clinical dementia.
AB  - Industry and academia are devoting a tremendous amount of resources to the
      testing of anti-inflammatory drugs for the treatment of Alzheimer's disease (AD).
      This trend is the result of the growing consensus supporting the inflammatory
      hypothesis of AD. If anti-inflammatory strategies succeed in slowing the rate of
      disease progression, the impact on patients and families could be enormous.
      However, given the large number of candidates in the pool of anti-inflammatory
      drugs and given their widely divergent activities, it is essential to use methods
      which optimizes drug selection and study design. Pilot studies of anti
      inflammatory regimens are useful in determining tolerability. However, these
      studies have limited value in estimating effective size since disease
      modification, rather than symptomatic improvement, is the ultimate goal. Better
      understanding of the influence of inflammatory activity and the specific
      mechanisms which play an early role in the progression of the disease, will
      improve the likelihood of successfully identifying an effective anti-inflammatory
      treatment strategy. This review outlines directions in research that address
      possible contributions of cyclooxygenase (COX)-2, COX-1 and other inflammatory
      mediators to AD neurodegeneration. Finally, this article addresses potential
      interventions designed to control segments of classical inflammatory cascades in
      the brain in which cyclooxygenase is highly implicated. These considerations are
      critical to understand the role of cyclooxygenase in the clinical progression of
      AD.

PMID- 11461719
TI  - Physician's attitudes towards disclosure of cancer diagnosis to elderly patients:
      a report from Tokyo, Japan.
AB  - Physicians' attitudes towards the disclosure of a cancer diagnosis to 114
      consecutive patients (age range, 65-93 years; median 78 years) admitted to the
      Tokyo Metropolitan Tama Geriatric Hospital from April 1994 to May 1995 were
      analyzed utilizing a questionnaire administered to the attending physicians.
      Eighty-seven patients (76%) had been informed of their diagnosis before the
      initiation of cancer treatment, while 27 patients (24%) were not told. 'To carry
      out the treatment under patient's understanding' and 'consideration for patient's
      quality of life' were the major reasons for diagnosis disclosure, while 'lack of
      patient's ability to understand the information' and 'family's wish that the
      patient not be informed of the truth' were the major reasons for non-disclosure.
      Dementia, deteriorated performance status, and non-curability were major factors
      related to non-disclosure. Even with decisional ability, 15% of patients were not
      told their cancer diagnosis because wishes of their families were preferred. The
      current results suggest that telling cancer diagnosis to the elderly patients
      will not yield negative attitude of the patients and that there is no rationale
      for physicians to hesitate to disclose cancer diagnosis merely because of
      patient's high age.

PMID- 11461720
TI  - Leg edema, ST-T abnormalities, and high BNP values are important signs of heart
      failure in the elderly.
AB  - This study was aimed at the mechanism of the circulatory failure characteristic
      of the elderly through elucidating the cause of leg edema frequently found in
      patients under treatment in health care facilities for physical or mental
      handicaps. ECG and measurement of atrial (ANP) and brain (BNP) natriuretic
      peptides were carried out on 156 patients (mostly females aged 84 years on
      average) and echocardiographic assessment was done on 44 patients. Non-specific
      ST-T abnormalities were frequently found in patients with moderate or severe leg
      edema (61 vs. 37% in those with slight or no edema). BNP levels were markedly
      increased in patients with either leg edema or ECG abnormalities (Group B) and
      with both (Group C) compared with those without either (Group A), with averages
      of 35.5+/-23.9, 91.3+/-80.1, and 184.3+/-139.0 pg/ml, respectively, for Group A,
      B, and C. UCG examination revealed marked regurgitation of cardiac valves, more
      frequently in patients with BNP over 50 pg/ml than in those with less (14/24 vs.
      2/20), with a difference in extent of 5.7 versus 1.6 on an arbitrary scale. In
      addition to left ventricular hypertrophy, dilatation of the left atrium and
      inferior vena cava was frequently observed in patients with higher BNP levels. It
      is concluded that both cardiac valve regurgitation and myocardial damage
      represented by ST-T abnormalities on ECG result in heart failure characteristic
      of the elderly, and that an increase in BNP is an important sign of such heart
      failure.

PMID- 11461721
TI  - Resisting the blame game: visualizing the high cost of dying and accepting the
      duty of technology stewardship for all patient populations. A review.
AB  - This article explores the concepts of therapy withholding and withdrawal as
      expressions of technology stewardship. With the world's geriatric population
      growing sharply, and advances in medical technology announced almost weekly, the
      time is ripe for the application of technology stewardship to patients of all
      ages, rather than arbitrary allocation limits for older persons. In life and in
      death, health care costs are expensive, and while society often views older
      people as too expensive to take care of alive, their death can be even more
      costly. For patients of all ages, death under the influence of technology is more
      expensive than life, yet it is geriatric intensive care medicine that grabs
      society's economic attention. While possibly not the financial bargain that
      arbitrary allocation limits have been proposed to be, technology stewardship
      fosters beneficence and autonomy as human values instead of mere variables
      subservient to economics.

PMID- 11461722
TI  - The involvement of hydroxyl free radicals in differentiation of the PC-12 rat
      pheochromocytoma cell line.
AB  - These experiments tested the differentiation properties of the PC-12 cell line
      under conditions of in vitro generation of OH&z.rad; free radicals by Fenton
      reaction. This involves the simultaneous addition of the following reactants: ADP
      Fe(2+)-complex (0.1 mM for iron) and H(2)O(2) (0.025 mM), final concentrations.
      Superoxide dismutase activity, the increase of which is considered as a marker of
      differentiation, catalase and glutathione peroxidase enzyme activities were
      investigated, which all displayed significant increases after single and repeated
      interventions with hydroxyl free radicals, while the cell number remained nearly
      at the starting-value. It is known that the differentiation takes place when the
      cell number has reached a plateau. These data, therefore, suggest that hydroxyl
      free radicals can induce in vitro cell differentiation, and that they play a more
      complex role in cell physiology than simply causing oxidative damages. It is
      interesting that the cells can maintain high levels of these enzyme activities
      for a relatively long time (2 or 4 days) after a very short flux of hydroxyl free
      radicals.

PMID- 11461723
TI  - Methodological issues and therapeutic perspectives in vascular dementia: a
      review.
AB  - Vascular dementia (VaD) is the most common form of dementia after Alzheimer's
      disease (AD). However, it is now increasingly recognized that not only is VaD a
      heterogeneous syndrome but also that VaD and AD are not mutually exclusive. Thus,
      the currently used criteria may no longer be sufficient for an accurate diagnosis
      of VaD. In addition, although it is widely assumed that risk factors for vascular
      disease are also risk factors for VaD, the evidence, in most cases, is
      circumstantial. For the effective prevention of VaD, therefore, large-scale and
      long-term clinical trials are required to investigate the validity of these
      putative risk factors. These trials should also include the VaD subtypes in their
      outcome measurements and to this end a simplified classification system should be
      adopted. Additional large-scale trials are required to facilitate the secondary
      prevention and symptomatic treatment of VaD, in particular to investigate the
      potential application of several nootropic and neuroprotective drugs. In both
      cases, these clinical trials should aim to move the field of VaD from opinion
      based medicine to evidence-based medicine.

PMID- 11461724
TI  - Odor threshold, recognition, discrimination and identification in centenarians.
AB  - The main purpose of this study was to learn the use of select measures that are
      relevant to olfactory discrimination, identification and recognition and to
      ascertain the appropriateness of extant methods and procedures for adaptation for
      use with the oldest-old. A second purpose of this study was to attempt initial
      examination of the relationship of different memorial systems in the oldest old
      through an atypical sensory modality. Twenty-one centenarians (mean=105.1 years)
      were tested on odor thresholds for phenethyl alcohol (PEA) and menthol,
      recognition and discrimination of lexically challenging odors, and identification
      of common odors. Chronological age was not found to be a significant predictor of
      abilities for any of the tasks. Thresholds for PEA and menthol were found to be
      better than anticipated levels and were associated with odor recognition and
      certainty of response. Mini Mental State Examination scores were not found to be
      associated with olfactory measures, contrary to expectations. Findings suggest
      much of the previous research into olfactorial abilities of older adults may have
      failed to account for the influence of illness, trauma, dementia and pathologies
      typically associated with age. In light of their performance on the tasks, the
      relative good health and cognitive status of the participants strengthens the
      idea that olfaction is an appropriate addition to diagnostic tests of Alzheimer's
      and other diseases.

PMID- 11461725
TI  - Quantitative electroencephalographic changes induced by odor detection and
      identification tasks: age related effects.
AB  - There are no previous studies which have compared quantitative
      electroencephalographic (QEEG) activity in young adult and normal elderly
      participants during olfactory tasks. This may be important if QEEG is to have a
      role in distinguishing between normal and pathological aging associated with this
      sensory system. Seventeen healthy elderly subjects (mean age 79.00+/-3.54 years)
      and 16 young adult controls (mean age 22.60+/-2.00 years) participated in the
      study. As reported in previous studies, beta1 and 2 activity was significantly
      greater in elderly subjects compared to young adults, thus confirming the
      reliability and validity of this study's quantitative electroencephalographic
      (QEEG) methodology. More alpha activity was evident in young adults compared with
      the elderly, whilst &theta; activity was distributed differently in the two age
      groups. These findings support previous literature suggesting EEG bandwidth
      activity reflect greater attentional capacity in young adults and EEG
      desynchronization in older people. Elderly subjects who identified two or fewer
      odors were found to have more beta activity in the olfaction condition compared
      to resting eyes closed, which may reflect cognitive impairment. These findings
      stress the importance of distinguishing subgroups of healthy elderly adults when
      examining the electroencephalographic profile.

PMID- 11461726
TI  - Angiotensin receptor blockers -- finally the evidence is coming in: IDNT and
      RENAAL.

PMID- 11461727
TI  - Survival following self-limited left ventricular free wall rupture during
      myocardial infarction. Management differences between patients with or without
      pseudoaneurysm formation.
AB  - The clinical, angiographic and therapeutic features of eight patients who
      developed a left ventricular pseudoaneurysm (PA) after an acute myocardial
      infarction (AMI) and those of 25 who did not develop this complication following
      a medically managed left ventricular free wall rupture (FWR) were compared. These
      25 patients were treated with pericardiocentesis, extended rest and strict blood
      pressure control. Most patients with FWR or PA had a first AMI and absence of
      overt heart failure. Both groups had a comparable age, frequency of systemic
      hypertension and extent of coronary disease. Pericardial effusion (> or =10 mm)
      was documented in all patients with FWR and in two of the three with PA with this
      information. Twenty four patients with FWR were hospitalized within the first 48
      h (96%) but only three of those with PA (37.5%, P<0.002). Moreover, in patients
      with PA, a FWR was not suspected during AMI and, as opposed to those with FWR,
      they did not undergo a strict blood pressure control or a restriction of physical
      activity following AMI. Also, beta blockers were administered to 15 patients with
      FWR (60%) but to only one with PA (11%, P<0.02). Our findings suggest that
      failure to recognise a self limited FWR during AMI and to provide adequate
      control of blood pressure and physical exercise during the acute phase and the
      early weeks postinfarction, are likely to favor development of PA.

PMID- 11461729
TI  - A randomised comparison of the use of 4 and 6 French diagnostic catheters: the
      limits of downsizing.
AB  - BACKGROUND: The use of small catheters for coronary angiography can reduce the
      risk of vascular complications and allow early ambulation, but excessive
      downsizing may lead to poor quality imaging. The aim of this study was to assess
      the feasibility of performing coronary angiography using 4 French (4 F) femoral
      catheters. METHODS: In total, 400 consecutive elective patients were randomised
      to undergo coronary angiography with 4 F or 6 F catheters. The puncture site was
      manually compressed and inspected before and after ambulation, and 24 h later.
      The handling difficulty of the catheters was semi-quantitatively evaluated using
      a three grade scoring system; angiogram quality was evaluated by two independent
      physicians. RESULTS: No major procedure-related complications were observed.
      Coronary arteriography with 4 F catheters was possible in all of the attempted
      cases. There were no statistical differences between the two groups in terms of
      procedural or fluoroscopy time, the amount of contrast medium used, or the
      incidence of vascular complications, while compression time was significantly
      shorter in the patients studied using the smaller catheter (3.4 vs. 9.9 min;
      P<0.0001). Catheter stability was similar in the two groups, whereas catheter
      torque and the quality of the coronary angiograms were statistically better in
      the patients studied using six French catheters. CONCLUSIONS: Coronary
      angiography with 4 F catheters is technically feasible and permits early
      ambulation after the procedure. Although the radiological resolution of the
      images obtained using 4 F catheters was always adequate for clinical decision
      making, the angiogram quality and catheter handling were significantly better
      using the 6 F system.

PMID- 11461731
TI  - Current perspectives on British use of adjunctive therapies during coronary
      interventions.
AB  - BACKGROUND: Interventional techniques are commonly performed with adjunctive
      therapy including clopidogrel, ticlopidine, abciximab and heparin. We wished to
      assess the current British use of antiplatelet and anticoagulant agents as
      adjunctive therapies in interventional cardiology in the light of the available
      evidence base regarding their usage. METHODS: A simple structured questionnaire
      was sent between August and October 1999 to all interventional cardiology
      consultants working in the UK regarding their usage of abciximab (ReoPro),
      heparin, clopidogrel (Plavix) and ticlopidine (Ticlid) peri-procedurally.
      RESULTS: 68% of consultants responded over the next 4 months, with many replying
      jointly for a centre rather than individually. Average abciximab use was 8.3% of
      interventional cases. Eighty-two percent of clinicians used clopidogrel in
      stented patients. Exact dosages varied considerably. Fifty-three percent of
      clinicians gave 10000 IU or more of heparin routinely. CONCLUSIONS: These figures
      are not in line with the published evidence and British interventionists appear
      to have adopted various strategies to target the use of these agents. In
      particular, abciximab appears to be being administered reactively, as and when
      problems arise in the catheterisation lab.

PMID- 11461733
TI  - A plea for harmonising guidelines.

PMID- 11461734
TI  - Retroesophageal aortic arch: diagnostic and therapeutic implications of a rare
      vascular ring.
AB  - Retroesophageal aortic arch (REAA) can be further divided to right or left
      retroesophageal aortic arch. The right REAA has right ascending and left
      descending aorta with retroesophageal segment, whereas the left REAA has left
      ascending and right descending aorta. The REAA with retroesophageal segment may
      cause tracheoesophageal compression by the formation of a vascular ring. A total
      of eight patients were identified from the database from 1996 to 1999. Among
      them, five were right REAA and three were left REAA. The age at diagnosis varied
      from 4 days to 16 years (median 8 years). The clinical findings and initial
      diagnostic investigations, including the chest X-ray, echocardiography and
      esophagogram, suspected the presence of this anomaly. The diagnosis can be
      confirmed by ultrafast computed tomography with or without three-dimensional
      reconstruction. Half of the total patients, two of right and two of left REAA
      were symptomatic and needed operation. The symptoms related to the
      retroesophageal aortic arch appeared during infancy and early childhood (six
      cases), and only rarely in late childhood and adults (two cases). Half of the
      patients were associated with congenital heart disease, but no specific patterns
      of congenital heart disease were identified. The sensitivity of the early
      diagnosis of REAA by chest roentgenogram, echocardiography, esophagogram and
      angiography was 37% (3/8), 0% (0/7), 100% (1/1) and 60% (3/5), respectively. The
      sensitivity of ultrafast CT was 100% (8) in delineating both retroesophageal
      segment and complete vascular ring. Operation to relieve the vascular compression
      was performed in two cases with right REAA and two with left REAA. Only one died
      after the operation, due to pulmonary arterial sling and tracheal stenosis. The
      surviving patients had been asymptomatic during follow up. In conclusion, REAA
      can be best diagnosed by ultrafast computed tomography with or without three
      dimensional reconstruction. If symptomatic, surgery to relieve the compression is
      effective and safe.

PMID- 11461735
TI  - Factors influencing late course of residual valvular and infundibular gradients
      following pulmonary valve balloon dilatation.
AB  - BACKGROUND: Though acute and follow-up benefits of pulmonary valve balloon
      dilatation (PVBD) for pulmonic valve stenosis are well known, the late course of
      residual gradients at individual valvular and infundibular levels is not well
      described. Furthermore, the factors influencing this late course have not been
      studied. MATERIALS AND METHODS: We assessed the transpulmonary gradients by echo
      Doppler in 96 patients (61 male, mean age 10.7 years) at a mean follow-up
      interval of 58.8+/-32.1 months (minimum 2 years) following PVBD. The patients
      were divided into three groups based on the residual gradients at valvular and
      infundibular levels immediately following PVBD as assessed by pull-back of an end
      hole catheter across the right ventricular outflow tract: Group A with minor
      pressure gradients at both valvular and infundibular levels of less than 30 mmHg
      (n=60, 62.5%), Group B with predominantly infundibular gradients of more than 30
      mmHg with a valvular gradient of less than 30 mmHg (n=27, 28.1%), and Group C
      with a residual valvular gradient of greater than 30 mmHg irrespective of the
      infundibular gradient (n=9, 9.4%). Demographic characteristics, hemodynamic
      parameters and procedural variables were correlated with the change in gradient
      at follow-up (late fall) and with long-term results. RESULTS: The mean follow-up
      trans-pulmonary gradient was 20+/-14 mmHg which was significantly lower than that
      immediately post-PVBD (43+/-32 mmHg), P<0.001. The late fall (mean 24+/-29, range
      -55 to 110 mmHg) varied widely depending upon the acute result group: patients in
      Groups A and B showed significant late fall of 9+/-12 mmHg (P<0.05 for follow-up
      gradient compared to that following PVBD) and 58+/-31 mmHg (P<0.0001),
      respectively, while patients in Group C showed an insignificant late fall of 14+/
      37 mmHg (P=0.21). In particular, each one of the patients in Group B showed
      decrease in trans-pulmonary gradients. On multivariate analysis, the extent of
      infundibular gradient emerged as the most important predictor of late fall
      (coefficient of determination 75%, P<0.0001). Patients who underwent PVBD at less
      than 2 years of age had a significantly greater late fall (41+/-33 mmHg) as
      compared to older patients (22+/-25 mmHg), P<0.05. A sub-optimal long-term result
      (transpulmonary gradient >25 mmHg, n=24) was significantly related to older age
      (P<0.001), dysplastic valve morphology (P=0.002), greater baseline trans
      pulmonary gradients (P<0.001) and higher post-PVBD gradients (P=0.04).
      CONCLUSIONS: The long-term course of patients following PVBD depends upon the
      site and magnitude of the residual gradients. Even high residual infundibular
      gradients show marked reduction at follow-up, especially in infancy.

PMID- 11461736
TI  - The relation between transmitral early filling wave deceleration time and the
      recovery of atrial contractility after electrical cardioversion of atrial
      fibrillation.
AB  - BACKGROUND: Electrical cardioversion of atrial fibrillation (AF) to sinus rhythm
      is associated with transient left atrial dysfunction and this phenomenon may lead
      to thrombus formation and embolic stroke. Delay of atrial mechanical function
      recovery may be related to ventricular diastolic function. OBJECTIVE: This study
      examined the effects of left ventricular diastolic function as well as the
      multiple clinical factors on the recovery of atrial systolic function after
      cardioversion for atrial fibrillation. METHODS: A total of 44 patients (28 male,
      16 female, 61+/-18 years) with chronic AF (> or =1 month) underwent electrical
      cardioversion. Deceleration time of early filling wave (pre-CV EDT) on
      transmitral inflow obtained by using Doppler echocardiography before
      cardioversion and serial transmitral inflow Doppler variables were recorded
      through a 1 week study period in all patients. Various clinical (age, gender, the
      duration of AF) and echocardiographic variables (pre-CV EDT, left atrial
      dimension, left ventricular ejection fraction) were tested for an association
      with peak atrial filling wave velocity (VA) on day 1, 3 and 7 after
      cardioversion. RESULTS: EDT measured before cardioversion had a strong linear
      correlation with peak VA on every echocardiographic evaluation after
      cardioversion (Regression coefficient (R)=0.69, P<0.001; R=0.78, P<0.001 and
      R=0.83, P<0.001, on day 1, day 3 and day 7, respectively). The effect of left
      ventricular ejection fraction on peak VA was weaker than those of EDT. The
      duration of AF showed an inverse association with the recovery of atrial
      function, but this lost on multivariate analysis. None of the other parameters
      significantly correlated with peak VA after cardioversion. CONCLUSION: The
      recovery of atrial mechanical function after cardioversion, as assessed by peak
      VA on transthoracic Doppler echocardiography is mainly associated with the left
      ventricular diastolic function as measured by EDT, whereas the left ventricular
      systolic function relatively a small effect on this outcome. The duration of AF
      does not have any association with peak VA, possibly if it is chronic.

PMID- 11461737
TI  - Low risk of significant echocardiographic valvulopathy in patients treated with
      anorectic drugs.
AB  - BACKGROUND: Phentermine--fenfluramine and dexfenfluramine use for weight loss has
      been previously associated with increased prevalence of valvular heart disease.
      This association was initially based on small numbers of patients, limited data
      on dose and duration of drug therapy, and no correlation with matched controls.
      METHODS: Our investigation involved 343 obese subjects enrolled in a prospective,
      strict weight loss, research protocol from September 1994 to September 1997. All
      subjects underwent transthoracic echocardiography for significant valvular
      lesions within a mean of 121 days from the manufacturer's announcement of the
      voluntary withdrawal of fenfluramine and dexfenfluramine from the market. All
      echocardiograms were interpreted by 2 independent readers. RESULTS: The study
      population included 281 females and 62 males with a mean age of 46.7+/-9.1 years
      and mean initial body mass index of 40.1+/-8.1 kg/m(2). Using the Food and Drug
      Administration's criteria, only 21 subjects (6.1%) had significant valvular
      lesions. Aortic regurgitation was detected in 18 subjects, mitral regurgitation
      in 3 subjects, and both aortic and mitral regurgitation in 1 subject; no one had
      severe regurgitation. Significant valvular disease did not correlate with age,
      gender, initial/ending body mass index, the drug dose, duration of drug therapy,
      or serotonin reuptake inhibitors. CONCLUSIONS: Anorexigen therapy is associated
      with a low prevalence of significant valvular regurgitation. Late valvular
      abnormalities from drug treatment await long term prospective studies.

PMID- 11461738
TI  - Propranolol treatment of congestive heart failure in infants with congenital
      heart disease: The CHF-PRO-INFANT Trial. Congestive heart failure in infants
      treated with propanol.
AB  - AIM: Infants with congenital heart disease and left-to-right shunts may develop
      significant clinical symptoms of congestive heart failure in spite of therapy
      with digoxin and diuretics. We investigated the effects of beta-blockade in
      infants with severe heart failure. METHODS AND RESULTS: We performed a
      prospective, randomized, open monocenter trial in infants treated with digoxin
      and diuretics (n=10) in comparison to 10 infants receiving additional beta
      blocker therapy. After 17 days on average beta-blocker treated infants
      (propranolol:1,6 mg/kg/day) improved significantly with respect to Ross heart
      failure score (3.3+/-2.3 vs. 8.3+/-1.9, P=0.002), lower renin levels (338+/-236
      vs. 704+/-490 microU/l, P=0.008) and lower mean heart rates in Holter ECG (118+/
      10 vs. 142+/-11 beats/min, P<0.001). While digoxin and diuretic treated infants
      had unchanged mean heart rate (149+/-8 vs. 148+/-10 beats/min), less decrease of
      symptoms (Ross Score: 8.5+/-1.7 vs. 6.8+/-2.3, P=0.02) but a significant increase
      of renin levels (139+/-102 vs. 938+/-607 microU/l, P=0.001). CONCLUSION:
      Additional propranolol treatment but not digoxin and diuretics alone can
      effectively reduce clinical symptoms of heart failure in infants with congenital
      heart disease, who suffer from increased neurohormonal activation.

PMID- 11461739
TI  - Intensive home-based exercise training in cardiac rehabilitation increases
      exercise capacity and heart rate variability.
AB  - BACKGROUND: Reduced heart rate variability (HRV) is a risk factor for cardiac
      death. Animal studies have shown increased HRV and reduced mortality after
      physical training. We evaluated the change in exercise capacity and HRV in
      cardiac rehabilitation patients, randomised to routine or home-based intensive
      training. The design was prospective, stratified randomisation with pre-specified
      subgroup analysis. METHODS: Maximal bicycle exercise test and 24-h Holter were
      performed 1 (baseline), 4 and 12 months after myocardial infarction (MI) or
      coronary artery by-pass surgery (CABG). Patients were randomised to physical
      training either two (N) or six (I) times per week for 3 months Sixty-two patients
      (43 MI and 19 CABG patients) were evaluated. RESULTS: Exercise capacity increased
      significantly more after 3 months of training in group I (mean (S.E.)); 29.0
      (3.4) vs. 7.2 (2.6) watts, P<0.001). One year later the difference in exercise
      capacity remained (26.5 (3.3) vs. 11.8 (3.8) watts, P<0.001). Global HRV
      measurements SDNN and SDANN increased significantly more in group I after
      training (17.1 (5.6) vs. 1.7 (3.7) and 16.2 (4.9) vs. 2.8 (3.1) ms, P<0.05) and 1
      year later the differences were still significant. Subgroup analysis showed more
      pronounced HRV response in CABG than MI patients. CONCLUSION: Intensive exercise
      training in cardiac rehabilitation increases exercise capacity and global HRV,
      which could be of prognostic significance.

PMID- 11461740
TI  - Recovery of electrophysiological parameters after conversion of atrial
      fibrillation.
AB  - We investigated the recovery of electrophysiological parameters from electrical
      remodeling after conversion of chronic lone atrial fibrillation in humans.
      Clinical studies have shown that the longer atrial fibrillation lasts, the more
      difficult it becomes to maintain the sinus rhythm after cardioversion. To explore
      the effects of the duration of atrial fibrillation on changes of
      electrophysiological parameters after conversion, we determined the atrial
      effective refractory period and P wave duration during right atrial pacing at 1
      and 24 h after electrical cardioversion in 15 patients with chronic lone atrial
      fibrillation (median duration, 6 months). By 24 h after cardioversion, the
      effective refractory period at a pacing cycle length of 600 ms increased from
      225+/-19 to 254+/-27 ms. However, the P wave duration did not decrease
      significantly 24 h after conversion. As the duration of atrial fibrillation
      became longer, the prolongation of effective refractory period was more delayed
      (P<0. 001, r=0.82), and the shortening of P wave duration was significantly
      smaller within 24 h after cardioversion (P<0. 001, r=0.67). After cardioversion
      of chronic lone atrial fibrillation, the recovery of shortened atrial
      refractoriness and prolonged intraatrial conduction time is dependent on the
      duration of preexisting atrial fibrillation.

PMID- 11461741
TI  - Chlamydia pneumoniae infection and its association with coronary heart disease
      and cardiovascular risk factors in a sample South Asian population.
AB  - Recent studies have suggested that a chronic infection with Chlamydia pneumoniae
      (C. pneumoniae) may be associated with the risk of developing coronary heart
      disease (CHD). A case control study was conducted to investigate the association
      between C. pneumoniae infection and coronary heart disease and coronary risk
      factors in a sample South Asian population. C. pneumoniae specific IgG antibody
      was measured by microimmunofluorescence. Among controls 56.6% were seropositive
      (> or =1/32) compared to 58.5% of acute myocardial infarction (AMI) patients
      (n=41, odds ratio 1.08, CI 0.37--3.12, P=0.93) and 73.3% of stable coronary heart
      disease (SCHD) patients (n=30, odds ratio 2.1, CI 0.63--7.19, P=0.27). The
      highest geometric mean titre of control subjects (n=30) was significantly lower
      (74.7) compared to AMI patients (101.5, P<0.05) and SCHD patients (138.6,
      P<0.05). Patients who were non-smokers had higher odds ratios for CHD than
      smokers when seropositive at IgG antibody titres of 1/32, 1/64 and 1/128,
      suggesting an association between smoking and C. pneumoniae infection. In
      patients with CHD there was a significant association between diabetes mellitus
      and seropositivity (P=0.008) in those over 50 years of age. Non-smoking CHD
      patients with high cholesterol/HDL-C ratio had a higher trend for seropositivity.
      Other risk factors (smoking, systolic and diastolic blood pressure, waist/hip
      ratio, triglycerides) showed no association when controlled for age. In the
      control group, smokers with high cholesterol/HDL-C ratio had a higher trend for
      seropositivity. These results do not provide strong support for the hypothesis
      that C. pneumoniae infection is a risk factor for clinical CHD in this South
      Asian population. Results suggest that C. pneumoniae infection may be linked to
      CHD through its interaction with some of the known risk factors such as blood
      lipids, diabetes and smoking.

PMID- 11461742
TI  - Long-term outcome of angioplasty for multivessel coronary disease: importance and
      price of complete revascularization.
AB  - BACKGROUND: Complete revascularization of multivessel coronary artery disease
      (MVD) by coronary artery bypass surgery has been shown to improve outcome, but
      there is a lack of similar data for patients treated by angioplasty. METHODS:
      Therefore, a consecutive series of 250 patients with MVD was separated into two
      groups, those with complete revascularization (n=101) and those with incomplete
      revascularization (n=149). Six-month 'clinical restenosis' rate assessed by
      stress myocardial perfusion scintigraphy or symptom-driven angiography and long
      term 32 months outcome were compared with an equally sized group of single vessel
      disease (SVD) patients. RESULTS: MVD patients with complete revascularization had
      a higher 'clinical restenosis' rate than patients with SVD (35 vs. 22%, P<0.02),
      although restenosis rate per treated vessel was similar (23%, 18%, P NS). If this
      higher early restenosis rate were accepted as 'price' for complete MVD
      angioplasty, long-term event-free survival was no longer different from that of
      SVD patients (86 vs. 93%, P NS). In contrast, patients with incomplete
      multivessel angioplasty had a significantly worse long-term outcome (22% events),
      especially if initially untreated, non-occluded vessels remained untreated (25%
      events). CONCLUSION: MVD angioplasty with complete revascularization has a long
      term event-free survival similar to that of SVD angioplasty but at the price of a
      higher rate of 6-month restenosis and repeat interventions.

PMID- 11461743
TI  - Impaired glucose metabolism predicts mortality after a myocardial infarction.
AB  - Diabetes is a risk factor for increased mortality after a myocardial infarction.
      Whether this applies for patients with hyperglycemia during the acute phase of a
      acute myocardial infarction is unclear. Therefore we determined the relation
      between admission plasma glucose level and mortality in a prospectively collected
      series of 336 consecutive AMI patients. Patients were divided in four groups
      based on WHO criteria for glucose levels: I: <5.6 mmol/l, II: 5.6--8.3 mmol/l,
      III: 8.4--11.0 mmol/l, IV: 11.1 mmol/l. The average age was 68+/-11 years with a
      peak CK of 1378+/-160 U/l, 34% were anterior wall AMIs and 52% were treated with
      thrombolysis. All patients had a long-term follow-up control at an average of
      14.2 months. One year mortality rate was 19.3% and rose to 44% in patients with
      glucose levels >11.1 mmol/l. The mortality was higher in diabetic patients than
      in non-diabetic patients (40 vs. 16%; P<0.05). Multivariate analysis revealed an
      independent effect of glucose level on mortality. In conclusions, our study in an
      unselected patient population demonstrates that admission plasma glucose level
      independently predicts 1 year mortality even in absence of diagnosed diabetes
      mellitus. Further studies evaluating the effect of acute insulin intervention in
      reducing mortality are warranted.

PMID- 11461744
TI  - Pravastatin reduces myocardial lesions induced by acute inhibition of nitric
      oxide biosynthesis in normocholesterolemic rats.
AB  - Pravastatin is useful in restoring endothelium-dependent relaxation in
      hypercholesterolemic animals. A single intravenous bolus injection of N(omega)
      nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthase,
      causes myocardial necrosis and reduces coronary flow in rats. Since rats do not
      develop hypercholesterolemia and atherosclerosis, we have tested the hypothesis
      that pravastatin protects the heart from myocardial lesions induced by L-NAME in
      the absence of alterations in cholesterol levels and plaque formation. Male
      Wistar rats fed standard chow were divided into four groups: CONTROL (n=14) -
      rats that received tap water alone for 18 days; L-NAME (n=14) -- rats that
      received L-NAME (15 mg/kg, i.v.) on the 14th day of the study; PRAVASTATIN (n=11)
      -- rats that received pravastatin (6 mg/kg/day) in their drinking water for 18
      days; PRAVASTATIN+L-NAME (n=12) -- rats that received pravastatin (6 mg/kg/day)
      and L-NAME (15 mg/kg, i.v.) as indicated in the preceding groups. At the end of
      18 days, the rats were sacrificed and the hearts removed for stereological
      analysis by light microscopy. Plasma nitrate/nitrite and thromboxane B(2)
      concentrations were determined immediately before and after L-NAME
      administration. Pravastatin prevented the ischemic lesions induced by the acute
      inhibition of NO biosynthesis (the area of myocardial lesions in the L-NAME group
      was greater than in the Pravastatin+L-NAME group: 101.6 microm(2) vs. 1.2
      microm(2), respectively; P<0.0001) and markedly increased the plasma
      nitrate/nitrate concentrations, even before L-NAME administration. There were no
      significant changes in the plasma thromboxane B(2) concentrations.

PMID- 11461745
TI  - Soluble P-selectin and the success of thrombolysis in acute myocardial
      infarction.
AB  - BACKGROUND: P-Selectin mediates adhesive interactions between platelets,
      leukocytes and endothelium to form thrombi. Our purpose was to investigate plasma
      soluble(s) P-selectin levels in patients with acute myocardial infarction (aMI)
      and the effect of thrombolysis on P-selectin levels. METHODS: Patients with aMI
      within the first 6 h of chest pain were enrolled prospectively. sP-selectin
      levels were determined by ELISA in the plasma of patients with aMI (n=32), stable
      angina (n=18), and healthy controls (n=15). Samples were obtained before, 3 and
      24 h after reperfusion therapy with tissue plasminogen activator. Seven patients
      showed recurrent angina or failure to reperfuse. RESULTS: sP-selectin levels were
      significantly higher in aMI group than other groups (86.7+/-8.7 ng/ml, P<0.05).
      sP-selectin levels were similar in stable angina and control groups (28.8+/-4.4
      vs. 25.4+/-7.3 ng/ml, P=NS). A significant increase in sP-selectin levels was
      observed 3 h after successful thrombolysis and this was followed by a decrease to
      near the baseline level late after reperfusion. But patients with failed
      reperfusion showed sustained high sP-selectin levels after 24 h of thrombolysis
      (P<0.05). CONCLUSION: The plasma sP-selectin level is elevated in aMI and it
      increases further following thrombolytic therapy. This increase is probably
      induced by activation of endothelial cells or platelets after myocardial ischemia
      and reperfusion during aMI. As the elevated levels are sustained in patients with
      failed reperfusion, serial P-selectin levels may be used as a non-invasive
      indicator of successful thrombolysis in aMI.

PMID- 11461746
TI  - Shift work modifies the circadian patterns of heart rate variability in nurses.
AB  - OBJECTIVE: The influence of shifting the work-sleep cycle on the circadian rhythm
      of cardiac autonomic activity was investigated by the spectral analysis of heart
      rate variability (HRV). METHODS: The subjects were 10 healthy Japanese female
      nurses aged 33+/-3 (S.D.) years. The subjects underwent ambulatory 24-h
      electrocardiogram (ECG) recordings on the days of day shift (working from 08:00
      to 17:00 h) and night shift (working from 21:40 to 08:40 h). Variables of the
      frequency domain of HRV were calculated for three activity states (work, awake
      but not working, and sleep). RESULTS: The mean values of HRV variables over 24 h
      were not different between day shift and night shift. For both shifts, variables
      related to the sympathetic control (low frequency component in normalized units
      and low/high frequency component ratio) were the largest during the work period
      and the smallest during the sleep period, while an opposite order was present for
      variables related to the vagal control (high frequency component in absolute
      value and normalized units). HRV variables in each activity state were not
      different between the two shifts. CONCLUSIONS: The circadian rhythm of cardiac
      autonomic activity is largely modified by the level of physical activity
      regardless of the clock hour, which may have clinical implications when studying
      the circadian fluctuations of the onset of cardiovascular disease in shift
      workers.

PMID- 11461747
TI  - Reproducibility of HTS-SQUID magnetocardiography in an unshielded clinical
      environment.
AB  - A new technology has been developed which measures the magnetic field of the
      human heart (magnetocardiogram, MCG) by using high temperature superconducting
      (HTS) sensors. These sensors can be operated at the temperature of liquid
      nitrogen without electromagnetic shielding. We tested the reproducibility of HTS
      MCG measurements in healthy volunteers. Unshielded HTS-MCG measurements were
      performed in 18 healthy volunteers in left precordial position in two separate
      sessions in a clinical environment. The heart cycles of 10 min were averaged,
      smoothed, the baselines were adjusted, and the data were standardized to the
      respective areas under the curves (AUC) of the absolute values of the QRST
      amplitudes. The QRS complexes and the ST-T intervals were used to assess the
      reproducibility of the two measurements. Ratios (R(QRS), R(STT)) were calculated
      by dividing the AUC of the first measurement by the ones of the second
      measurement. The linear correlation coefficients (CORR(QRS), CORR(STT)) of the
      time intervals of the two measurements were calculated, too. The HTS-MCG signal
      was completely concealed by the high noise level in the raw data. The averaging
      and smoothing algorithms unmasked the QRS complex and the ST segment. A high
      reproducibility was found for the QRS complex (R(QRS)=1.2+/-0.3, CORR(QRS)=0.96+/
      0.06). Similarly to the shape of the ECG it was characterized by three bends, the
      Q, R, and S waves. In the ST-T interval, the reproducibility was considerably
      lower (R(STT)=0.9+/-0.2, CORR(STT)=0.66+/-0.28). In contrast to the shape of the
      ECG, a baseline deflection after the T wave which may belong to U wave activity
      was found in a number of volunteers. HTS-MCG devices can be operated in a
      clinical environment without shielding. Whereas the reproducibility was found to
      be high for the depolarization interval, it was considerably lower for the ST
      segment and for the T wave. Therefore, before clinically applying HTS-MCG systems
      to the detection of repolarization abnormalities in acute coronary syndromes,
      further technical development of the systems is necessary to improve the signal
      to-noise ratio.

PMID- 11461748
TI  - Meta-analyses of prospective studies on coronary heart disease, type A
      personality, and hostility.
AB  - BACKGROUND: Several large-scale prospective studies have failed to find an
      association between Type A personality (TAP) or hostility and coronary heart
      disease (CHD). The existing meta-analyses on this topic have several
      shortcomings, such as a selective search of the literature, the failed use of
      effect sizes, and methodological flaws. METHODS: The present meta-analyses cover
      all prospective studies until the end of 1998. The correlation coefficient r is
      used as effect size to yield information on the population effect size R and
      variance. Several analyses have been carried out to stratify for disease
      endpoints, samples (healthy population, CHD patients), and methods used to
      determine TAP or hostility. RESULTS: The population effect size (weighted average
      of all correlation coefficients) for TAP and CHD is R=0.003 (n=74,326, P=0.213),
      and for hostility and CHD R=0.022 (n=15,038, P=0.003). CONCLUSIONS: The
      population effect size for TAP and CHD is not significant. Hostility yields a
      significant association with CHD; however, the effect size is so low that it has
      as yet no practical meaning for prediction and prevention.

PMID- 11461749
TI  - Clinical determinants of increased QT dispersion in patients with diabetes
      mellitus.
AB  - AIMS: To compare QT dispersion measurements in diabetic patients to control
      subjects and assess any associations between QT dispersion and diabetic clinical
      characteristics. METHODS: A total of 512 diabetics and 50 age and gender matched
      controls were studied. QT interval was measured manually in 12-lead conventional
      electrocardiograms, and QT dispersion (QTd), heart rate-corrected QT dispersion
      (QTcd), number of leads-adjusted QT dispersion (adjuQTd) and adjacent QT
      dispersion (adjaQTd) were calculated. Demographic, clinical, laboratory and
      electrocardiographic data were recorded. RESULTS: Diabetics showed increased QT
      dispersion compared to controls (QTd: P<0.001, QTcd: P<0.001, adjuQTd: P<0.001),
      even those with recent diagnosis (less than 2 years) and without arterial
      hypertension, ECG abnormalities or chronic degenerative complications (QTd:
      P=0.01, QTcd: P<0.001, adjuQTd: P=0.04). Left ventricular hypertrophy (QTd:
      P<0.001, QTcd: P<0.001, adjuQTd: P<0.001, adjaQTd: P<0.001) and conduction
      disturbances (QTd: P=0.002, QTcd: P=0.003, adjuQTd: P=0.003) were the
      electrocardiographic findings associated with increased QT dispersion in
      bivariate analysis. Clinical variables were the presence of arterial hypertension
      (QTd: P=0.004, QTcd: P=0.01, adjuQTd: P<0.001), even without left ventricular
      hypertrophy (QTd: P=0.01, QTcd: P=0.03, adjuQTd: P=0.003), and the presence of
      diabetic cardiovascular complications (QTd: P=0.02, QTcd: P=0.01, adjuQTd:
      P=0.008, adjaQTd: P=0.03). No association between QT dispersion and the presence
      of diabetic microvascular complications, glycaemic control, age and gender, or
      cardiovascular drugs was observed. Multivariate regressive statistical analysis
      confirmed the associations noted in bivariate analysis. CONCLUSIONS: Diabetic
      patients have increased QT dispersion compared to non-diabetics even those
      without arterial hypertension and cardiovascular complications and with recent
      diagnosis. The presence of arterial hypertension, diabetic cardiovascular
      complications and electrocardiographic abnormalities of left ventricular
      hypertrophy and conduction disturbances were associated to increased QT
      dispersion in diabetes mellitus.

PMID- 11461750
TI  - A saccular aneurysm on the ascending aorta following aortic valve replacement.

PMID- 11461751
TI  - Pathophysiology of vascular endothelium and circulating platelets: implications
      for coronary revascularisation and treatment.
AB  - Constant vasodilatation, inhibition of platelet and leukocyte adhesion, and local
      thrombolysis are the mechanisms through which an intact endothelial layer exerts
      its protective action on coronary circulation. A loss in these features is not
      only the first step in the development of atherosclerosis, but also a potent
      trigger for complications after revascularisation procedures. Percutaneous
      coronary interventions, particularly in the course of stenting, induce
      endothelial injury that can last up to months after the procedure. On the other
      hand, the preservation of endothelial function appears the best feature of
      arterial versus venous grafts after coronary bypass surgery. An early diagnosis
      either by invasive or non-invasive techniques has important implications for
      prognosis, and endothelial dysfunction can be effectively counteracted by medical
      treatment (ACE inhibitors, statins). Activated circulating platelets are present
      in the course of coronary artery disease, increasing the risk of thrombotic
      occlusion and/or plaque regrowth, after both percutaneous and surgical
      revascularisation. New antiplatelet agents are under development to reduce
      endothelium-platelet interaction. On the basis of the latest studies, coronary
      revascularisation should be integrated in a more complete treatment, which would
      take into account the complex processes involving the underlying atherosclerotic
      plaque.

PMID- 11461752
TI  - Activation of matrix metalloproteinase dilates and decreases cardiac tensile
      strength.
AB  - Previous studies demonstrated that transition from compensatory pressure overload
      hypertrophy to decompensatory volume overload heart failure is associated with
      decreased cardiac tensile strength and activation of matrix metalloproteinase
      (MMP) in spontaneously hypertensive rat (SHR). To test the hypothesis that in the
      absence of nitric oxide activation of MMP during cardiac failure causes
      disruption in the organization of extracellular matrix (ECM) and leads to
      decrease systolic and diastolic cardiac tensile strength, we employed SHR of 24-
      32 weeks, which demonstrates significant cardiac hypertrophy and fibrosis. The
      normotensive Wistar rats (NWR) were used as control. To determine whether cardiac
      hypertrophy is associated with increased elastinolytic matrix metalloproteinase-2
      (MMP-2) activity; quantitative elastin-zymography was performed on cardiac tissue
      homogenates. The MMP-2 activity was normalized by the levels of actin. The MMP
      2/actin ratio was 2.0+/-0.5 in left ventricle (LV) and 1.5+/-0.25 in right
      ventricle (RV) of SHR(32wks); and 0.5+/-0.25 in LV and 0.25+/-0.12 in RV of
      NWR(32wks) (P<0.02 when SHR compared with NWR). To measure passive diastolic
      cardiac function, rings from LV as well as RV through transmyocardial wall from
      male SHR and NWR of 6--8 weeks and 24--36 weeks were prepared. The LV wall
      thickness from endocardium to epicardium was 3.75+/-0.25 mm in SHR(32wks) as
      compared to 2.25+/-0.50 mm in NWR(32wks) (P<0.01). The ring was placed in tissue
      myobath and length--tension relationships were assessed. The pressure--length
      relationship was shifted to left in SHR as compared to NWR. The amounts of
      cardiac elastin and collagen were determined spectrophotometrically by measuring
      desmosine--isodesmosine and hydroxyproline contents, respectively. A negative
      correlation between elastic tensile strength and elastin/collagen ratio was
      elucidated. To create situation analogous to heart failure and MMP activation, we
      treated cardiac rings with active MMP-2 and length--tension relation was
      measured. The relationship was shifted to right in both SHR and NWR when compared
      to their respective untreated groups. The results suggested that activation of
      MMP led to decreased cardiac tissue tensile strength and may cause systolic and
      diastolic dysfunction.

PMID- 11461753
TI  - Intravenous magnesium sulfate versus diltiazem in paroxysmal atrial fibrillation.
AB  - BACKGROUND: Drugs currently available for the acute treatment of paroxysmal
      atrial fibrillation have significant limitations. We assessed the safety and
      effectiveness of intravenous magnesium sulfate versus diltiazem therapy in
      patients with prolonged episodes of paroxysmal atrial fibrillation. METHODS: In a
      prospective randomized trial, 46 symptomatic patients presenting with paroxysmal
      atrial fibrillation were given intravenous magnesium sulfate (n=23) or diltiazem
      (n=23) therapy. Primary outcome measures were effects on ventricular rate control
      and proportion of patients restored to sinus rhythm at 6 h after initiation of
      treatment. RESULTS: There were no differences in baseline characteristics between
      the two groups. Both forms of treatment were well tolerated, with no adverse
      clinical events. Both drugs had similar efficacy in reducing the ventricular rate
      at the first hour of treatment (P<0.05) with a tendency toward a further decrease
      during infusion times of 2 (P<0.01), 3, 4, 5 and 6 h, respectively (P<0.001).
      However, at the end of the 6-h treatment period, restoration of sinus rhythm was
      observed in a significantly higher proportion of patients in the magnesium group
      compared with the diltiazem group [13 of 23 patients, (57%), versus five of 23
      patients, (22%), P=0.03]. CONCLUSIONS: Magnesium sulfate favorably affects rate
      control and seems to promote the conversion of long lasting episodes of
      paroxysmal atrial fibrillation to sinus rhythm, representing a safe, reliable and
      cost-effective alternative treatment strategy to diltiazem.

PMID- 11461754
TI  - Intracoronary electrocardiogram for early detection of myocardial viability
      during coronary angioplasty in acute myocardial infarction.
AB  - PURPOSE: The clinical value of the intracoronary electrocardiogram (ECG) for
      detecting myocardial viability in acute myocardial infarction was evaluated by
      thallium-201 scintigraphy and left ventriculogram at the chronic stage. METHODS:
      Intracoronary ECGs, recorded from the tip of a guidewire during emergency
      coronary angioplasty, were obtained in 65 patients with reperfused anterior
      myocardial infarction. Further ST segment elevation of greater than 0.2 mV
      detected during the balloon inflation was taken as significant. The left
      ventricular segmental shortening was measured from left ventriculograms recorded
      at acute and chronic stages. The infarct area was defined as viable when a
      thallium uptake of more than 50% was detected on thallium-201 myocardial
      scintigraphy at the chronic stage. RESULTS: During emergency coronary
      angioplasty, significant ST segment elevation was noted in 45 patients (Group A);
      however, the ST segment was not significantly elevated in the other 20 patients
      (Group B). The infarct area of 42 patients in Group A and three patients in Group
      B was viable on scintigraphy. Improvement left ventricular wall motion of the
      infarct area was observed in 39 of the 42 patients in Group A and the three
      patients in Group B. Therefore, intracoronary ECG can predict reversible
      dysfunction with excellent sensitivity (92.9%) and specificity (73.9%).
      CONCLUSIONS: The myocardium within an infarct area can be regarded as viable when
      a further ST segment elevation occurs on intracoronary ECG during emergency
      coronary angioplasty. It is useful, therefore, to monitor the intracoronary ECG
      during coronary angioplasty balloon inflation to assess the myocardial viability
      of the infarct area.

PMID- 11461755
TI  - Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new
      synthetic methodology for methylphenidate analogs based on the Blaise reaction.
AB  - In order to make new analogs of the dopamine (DA) uptake inhibitor
      methylphenidate, a synthetic methodology based on the Blaise reaction was
      developed. The reaction between alpha-bromophenylacetic acid esters, zinc and
      alpha-cyano-omega-mesylates gave stable primary enamines. After reduction of the
      enamines with cyanoborohydride, the amines could be cyclized to methylphenidate
      analogs in which the amine ring size and aromatic ring were varied. These
      compounds were tested for inhibitory potency against [(3)H]WIN 35,428 binding to
      the cocaine recognition site and [(3)H]DA uptake using rat striatal tissue. When
      the heterocyclic ring size was varied, the six-membered ring of methylphenidate
      appeared to be the optimum ring size. When the aryl ring was varied the 4
      trifluoromethylphenyl analog was less potent than methylphenidate, the beta
      naphthyl congener was considerably more potent, whereas the alpha-naphthyl
      congener was less potent. Most of the compounds tested had ratios of uptake to
      binding inhibition (discrimination ratio) that were similar to cocaine and were
      therefore not lead compounds for the development of cocaine antagonists.

PMID- 11461756
TI  - Synthesis and antimicrobial activities of new pyridinium and benzimidazolium
      chlorides.
AB  - A novel class of pyridinium and benzimidazolium chloride has been obtained in
      high yield. The antimicrobial activities of three homologous series of pyridinium
      and benzimidazolium chlorides against cocci, rods, fungi and bacillus have been
      measured. The antimicrobial activities of N,N'-bis[3-(1-alkoxymethyl)pyridinium
      chloride]methylenediamines, 1-undecyloxymethyl-3-(1
      benzimidazolmethylamino)pyridinium, 1-undecyloxymethyl- and 1-dodecyloxymethyl-3
      [1(benzotriazol-1-yl)methylamino]pyridinium chlorides exhibited strong activity
      and wide antibacterial spectra similar to the activity of benzalkonium chloride.

PMID- 11461757
TI  - Pyrazolopyrimidines: synthesis, effect on histamine release from rat peritoneal
      mast cells and cytotoxic activity.
AB  - A series of 1H-pyrazolo[3,4-d]pyrimidines (3--6) substituted at positions 1
      (R(1)=Ph, H, tert-butyl and ribosetribenzoate), 4 (R(2)=chlorine, nitrogen and
      oxygen nucleophiles), and 6 (dimethylamino) have been synthesized and their
      effect on the release of histamine from rat peritoneal mast cells measured. After
      chemical stimulation, (polymer 48/80), several compounds (i.e. 3b, 4a, 4b, 4d,
      4g, 5a), produce inhibition two to three times higher (40--60%) than DSCG but
      this action is lower after preincubation. 4b (R(1)=Ph, R(2)=NHCH(2)Ph; 50--70%
      inhibition) and 5a (R(1)=H, R(2)=OMe; 50--55% inhibition) are the most active
      ones in both experiments. With ovoalbumin as stimulus, several
      pyrazolopyrimidines show inhibition similar to DSCG, the most active compounds
      being 6a--d (IC(50)=12--16 microM; R(1)=ribosetribenzoate, R(2)=methoxy and
      amino). Compounds 4e (R(1)=t-butyl, R(2)=OMe) and 4g (R(1)=t-butyl,
      R(2)=piperidino) are inducers of the release of histamine (60 and 150% increase).
      Compounds 4b and 4c showed cytotoxic activity (IC(50)=1 microg/mL) to HT-29 human
      colon cancer cells.

PMID- 11461758
TI  - CoMFA of benzyl derivatives of 2,1,3-benzo and benzothieno[3,2-alpha]thiadiazine
      2,2-dioxides: clues for the design of phosphodiesterase 7 inhibitors.
AB  - A CoMFA study of benzo- and benzothienothiadiazines derivatives as
      phosphodiesterase 7 inhibitors has been carried out in order to determine the
      factors required for the activity of these compounds and also for the selectivity
      versus other phosphodiesterase isoenzymes. This methodology is employed to gain
      clues on the design of new fused thiadiazines with improved activity and
      selectivity on phosphodiesterase 7. Using the information achieved from the three
      CoMFA models, new structures have been designed in silico and their inhibitory
      activity on phosphodiesterase 7 was predicted.

PMID- 11461759
TI  - New lanthanide complexes of 4-methyl-7-hydroxycoumarin and their pharmacological
      activity.
AB  - Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7
      hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of
      equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin
      sodium salt in water. The complexes were characterized and identified by
      elemental analysis, conductivities, IR, (1)H and (13)C NMR spectroscopies and
      mass spectral data. DTA and TGA have been applied to study the compositions of
      the compounds. The newly synthesized compounds were assayed for acute
      intraperitoneal and per oral toxicity, influence on blood clotting time and the
      most active complex was investigated for spasmolytic activity. The complexes of
      cerium(III) and neodymium(III) showed marginal cytotoxic activity against
      transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic
      salts.

PMID- 11461760
TI  - Database mining applied to central nervous system (CNS) activity.
AB  - A data set of 389 compounds, active in the central nervous system (CNS) and
      divided into eight classes according to the receptor type, was extracted from the
      RBI database and analyzed by Self-Organizing Maps (SOM), also known as Kohonen
      Artificial Neural Networks. This method gives a 2D representation of the
      distribution of the compounds in the hyperspace derived from their molecular
      descriptors. As SOM belongs to the category of unsupervised techniques, it has to
      be combined with another method in order to generate classification models with
      predictive ability. The fuzzy clustering (FC) approach seems to be particularly
      suitable to delineate clusters in a rational way from SOM and to get an automatic
      objective map interpretation. Maps derived by SOM showed specific regions
      associated with a unique receptor type and zones in which two or more activity
      classes are nested. Then, the modeling ability of the proposed SOM/FC Hybrid
      System tools applied simultaneously to eight activity classes was validated after
      dividing the 389 compounds into a training set and a test set, including 259 and
      130 molecules, respectively. The proper experimental activity class, among the
      eight possible ones, was predicted simultaneously and correctly for 81% of the
      test set compounds.

PMID- 11461761
TI  - Esters of chlorambucil with 2-substituted 1,4-dihydroxy-9,10-anthraquinones as
      multifunctional anticancer agents.
AB  - Novel twelve esters of chlorambucil with 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10
      anthraquinone were synthesized and tested for their antitumor activity in mice
      bearing S-180 ascitic cells as well as cytotoxic activity against L1210 cells.
      Eight of them were highly cytotoxic on L1210 cells (ED(50), <6 microg mL(-1)) and
      derivatives 1 and 12 (T/C, 200 and 205%) appeared more active in vivo than
      chlorambucil (T/C, 168%).

PMID- 11461762
TI  - Synthesis and biological evaluation of first N-alkyl syn dimeric 4-aryl-1,4
      dihydropyridines as competitive HIV-1 protease inhibitors.
AB  - A first series of novel N-alkyl substituted syn dimeric 4-aryl-1,4
      dihydropyridines 12--17 have been synthesised and evaluated as HIV-1 protease
      inhibitors in in vitro assays. While the N-methyl derivatives 12 and 13 were
      almost inactive, with IC(50)-values of about 225 microM, the N-benzyl compounds
      with varied ester groups all exhibited stronger activities, with IC(50)-values of
      11--12 microM for the presently best compounds 16 and 17 with ethyl ester
      functions. The type of HIV-1 protease inhibition of the novel inhibitors was
      characterised as competitive. With the increase of observed activity from N
      methyl derivatives to N-benzyl compounds the binding mode may correspond to that
      of cyclic ureas with hydrophobic interactions of the four aromatic residues to
      the S1/S1' and S2/S2' regions of HIV-1 protease.

PMID- 11461763
TI  - Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric
      thiocytisine as potent and selective nAChR ligands.
AB  - We have developed one-step syntheses of halogenated derivatives of (-)-cytisine
      featuring a halogen substituent at positions 3, 5 or 3 and 5 of the 2-pyridone
      fragment, and prepared the novel bioisosteric thiocytisine by oxygen-sulphur
      exchange. The affinities of these pyridone-modified analogs of (-)-cytisine for
      (alpha 4)(2)(beta 2)(3) and alpha 7* nAChRs in rat forebrain membranes were
      determined by competition with (+/-)-[(3)H]epibatidine and [(3)H]MLA,
      respectively. The 3-halocytisines 7 possess subnanomolar affinities for (alpha
      4)(2)(beta 2)(3) nAChRs, higher than those found for (-)-cytisine as well as for
      the 5-halocytisines 8 and 3,5-dihalocytisines 6. In contrast to the parent
      alkaloid the 3-halogenated species display much a higher affinity for the alpha
      7* nAChR subtype. The most potent molecule was 3-bromocytisine (7b) with
      preferential selectivity (200-fold) for the (alpha 4)(2)(beta 2)(3) subtype
      [K(i)=10 pM (alpha 4 beta 2) and 2.0 nM (alpha 7*)]. Replacement of the lactam
      with a thiolactam pharmacophore to thiocytisine (12) resulted in a subnanomolar
      affinity for the (alpha 4)(2)(beta 2)(3) nAChR subtype (K(i)=0.832 nM), but in a
      drastic decrease of affinity for the alpha 7* subtype; thiocytisine (12) has a
      K(i) value of 4000 nM (alpha 7*), giving a selectivity of 4800-fold for the
      neuronal (alpha 4)(2)(beta 2)(3)-nAChR and thus displaying the best affinity
      selectivity profile in the series under consideration.

PMID- 11461764
TI  - Antitumor agents. Synthesis and biological evaluation of new compounds related to
      podophyllotoxin, containing the 2,3-dihydro-1,4-benzodioxin system.
AB  - New compounds with naphtho-fused systems were synthesized and evaluated as
      antitumor agents. The naphtho-fused systems 6 and 7, synthesized from the hydroxy
      acetal, exhibit antitumor activity. The bis(phenylthio) derivatives were
      considered as possible precursors for lignan lactones (11). The hydroxy
      naphthalen 6 showed a significant antineoplastic activity.

PMID- 11461765
TI  - Ca(2+)-calmodulin antagonist chlorpromazine and poly(ADP-ribose) polymerase
      modulators 4-aminobenzamide and nicotinamide influence hepatic expression of BCL
      XL and P53 and protect against acetaminophen-induced programmed and unprogrammed
      cell death in mice.
AB  - Acetaminophen (AAP), the analgesic hepatotoxicant, is a powerful inducer of
      oxidative stress, DNA fragmentation, and apoptosis. The anti-apoptotic oncogene
      bcl-XL, and the pro-apoptotic oncogene p53 are two key regulators of cell cycle
      progression and/or apoptosis subsequent to DNA damage in vitro and in vivo. This
      study investigated the effect of AAP on the expression of these oncogenes and
      whether agents that modulate DNA fragmentation (chlorpromazine, CPZ) and DNA
      repair through poly(ADP-Ribose) polymerase (PARP) activity (4-AB: 4
      aminobenzamide) can protect against AAP-induced hepatotoxicity by inhibiting
      oxidative stress, DNA fragmentation, and/or by altering the expression of bcl-XL
      and p53. In addition, the protective effect of supplemental nicotinamide (NICO),
      known to be depleted in cells with high PARP activity during DNA repair, is
      similarly evaluated. Male ICR mice (3 months old) were administered vehicle
      alone; nontoxic doses of 4-AB (400 mg/kg, ip), NICO (250 mg/kg, ip) or CPZ (25
      mg/kg, ip), hepatotoxic dose of AAP alone (500 mg/kg, ip), or AAP plus one of the
      protective agents 1 h later. All animals were sacrificed 24 h following AAP
      administration. Serum alanine aminotransferase activity (ALT), hepatic
      histopathology and lipid peroxidation, DNA damage, and expression of bcl-XL and
      p53 (western blot analysis) were compared in various groups. All of the three
      agents significantly prevented AAP-induced liver injury, lipid peroxidation, DNA
      damage, and associated apoptotic and necrotic cell deaths, 4-AB being the most
      effective and NICO the least. Compared to control, there was a considerable
      decrease in bcl-XL expression, and an increase in p53 expression in AAP-exposed
      livers. The effect of AAP on bcl-XL was antagonized and that on p53 was
      synergized by the PARP-modulator 4-AB as well as NICO, whereas the endonuclease
      inhibitor CPZ was without effect on either bcl-XL or p53 expression. These
      results suggest that the hepatotoxic effect of AAP involves multiple mechanisms
      including oxidative stress, upregulation of endonuclease (or caspase-activated
      DNAse) and alteration of pro- and anti-apoptotic oncogenes. The observed
      antagonism of AAP-induced hepatocellular apoptosis and/or necrosis by modulators
      of multiple processes including DNA repair suggests the likelihood that a more
      effective therapy against AAP intoxication should involve a combination of
      antidotes.

PMID- 11461766
TI  - Oxidation of active center cysteine of bovine 1-Cys peroxiredoxin to the cysteine
      sulfenic acid form by peroxide and peroxynitrite.
AB  - Peroxiredoxins are antioxidant enzymes whose peroxidase activity depends on a
      redox-sensitive cysteine residue at the active center. In this study we
      investigated properties of the active center cysteine of bovine 1-Cys
      peroxiredoxin using a recombinant protein (BRPrx). The only cysteine residue of
      the BRPrx molecule was oxidized rapidly by an equimolar peroxide or peroxynitrite
      to the cysteine sulfenic acid. Approximate rates of oxidation of BRPrx by
      different peroxides were estimated using selenium glutathione peroxidase as a
      competitor. Oxidation of the active center cysteine of BRPrx by H2O2 proceeded
      only several times slowly than that of the selenocysteine of glutathione
      peroxidase. The rate of oxidation varied depending on peroxides tested, with H2O2
      being about 7 and 80 times faster than tert-butyl hydroperoxide and cumene
      hydroperoxide, respectively. Peroxynitrite oxidized BRPrx slower than H2O2 but
      faster than tert-butyl hydroperoxide. Further oxidation of the cysteine sulfenic
      acid of BRPrx to higher oxidation states proceeded slowly. Oxidized BRPrx was
      reduced by dithiothreitol, dihydrolipoic acid, and hydrogen sulfide, and
      demonstrated peroxidase activity (about 30 nmol/mg/min) with these reductants as
      electron donors. beta-Mercaptoethanol formed a mixed disulfide and did not
      support peroxidase activity. Oxidized BRPrx did not react with glutathione,
      cysteine, homocysteine, N-acetyl-cysteine, and mercaptosuccinic acid.

PMID- 11461767
TI  - Intestinal release and uptake of phenolic antioxidant diferulic acids.
AB  - Diferulic acids are potent antioxidants and are abundant structural components of
      plant cell walls, especially in cereal brans. As such, they are part of many
      human and animal diets and may contribute to the beneficial effect of cereal
      brans on health. However, these phenolics are ester-linked to cell wall
      polysaccharides and cannot be absorbed in this form. This study provides the
      first evidence that diferulic acids can be absorbed via the gastrointestinal
      tract. The 5-5-, 8-O-4-, and 8-5-diferulic acids were identified in the plasma of
      rats after oral dosing with a mixture of the three acids in oil. Our study also
      reveals that human and rat colonic microflora contain esterase activity able to
      release 5-5-, 8-O-4-, and 8-5-diferulic acids from model compounds and dietary
      cereal brans, hence providing a mechanism for release of dietary diferulates
      prior to absorption of the free acids. In addition, cell-free extracts from human
      and rat small intestine mucosa exhibited esterase activity towards diferulate
      esters. Hence, we have shown that esterified diferulates can be released from
      cereal brans by intestinal enzymes, and that free diferulic acids can be absorbed
      and enter the circulatory system. Our results suggest that the phenolic
      antioxidant diferulic acids are bioavailable.

PMID- 11461768
TI  - Catecholamines inhibit lipid peroxidation in young, aged, and Alzheimer's disease
      brain.
AB  - Some catecholamines and indolamines inhibit lipid peroxidation. Recent studies
      indicate that catecholaminergic inhibition of lipid peroxidation may be receptor
      mediated in vivo and in cell cultures. Because oxidative stress is one of the
      hypothesized pathogenic mechanisms for neurodegenerative diseases, including
      Alzheimer's disease (AD), we hypothesized that catecholaminergic and
      indolaminergic inhibition of lipid peroxidation would be altered in AD as
      compared to age-matched non-AD. To test this hypothesis we studied the effect of
      a variety of neurotransmitters and their antagonists on ascorbate-stimulated
      lipid peroxidation in membrane fragment preparations derived from postmortem
      human brain. In this in vitro system, the inhibition of lipid peroxidation by
      dopamine and serotonin did not appear to be receptor mediated. Further, our
      findings indicate that there is no apparent effect of age or AD on the inhibition
      of lipid peroxidation by catecholaminergic and indolaminergic agents.

PMID- 11461769
TI  - Arsenite induces oxidative DNA adducts and DNA-protein cross-links in mammalian
      cells.
AB  - Arsenic is generally recognized as a nonmutagenic carcinogen because sodium
      arsenite induces DNA damage only at very high concentrations. In this study we
      demonstrate that arsenite concentrations above 0.25 microM induce DNA strand
      breaks in both human leukemia cells and Chinese hamster ovary cells. Therefore,
      DNA damage may be involved in arsenic-induced carcinogenesis. Formamidopyrimidine
      DNA glycosylase and proteinase K greatly increased DNA strand breaks in arsenite
      treated cells, providing evidence that a large portion of arsenite-induced DNA
      strand breaks come from excision of oxidative DNA adducts and DNA-protein cross
      links. Because DNA strand breaks appear only temporarily during excision repair,
      the level of detectable DNA strand breaks will be low at any given time point.
      For this reason many previous studies have only detected low levels of DNA strand
      breaks. We also show that catalase, and inhibitors of calcium, nitric oxide
      synthase, superoxide dismutase, and myeloperoxidase, could modulate arsenite
      induced DNA damage. We conclude that arsenite induces DNA adducts through calcium
      mediated production of peroxynitrite, hypochlorous acid, and hydroxyl radicals.

PMID- 11461770
TI  - Reaction conditions affecting the relationship between thiobarbituric acid
      reactivity and lipid peroxides in human plasma.
AB  - The thiobarbituric acid (TBA) reactivity of human plasma was studied to evaluate
      its adequacy in quantifying lipid peroxidation as an index of systemic oxidative
      stress. Two spectrophotometric TBA tests based on the use of either phosphoric
      acid (pH 2.0, method A) or trichloroacetic plus hydrochloric acid (pH 0.9, method
      B) were employed with and without sodium sulfate (SS) to inhibit sialic acid (SA)
      reactivity with TBA. To correct for background absorption, the absorbance values
      at 572 nm were subtracted from those at 532 nm, which represent the absorption
      maximum of the TBA:MDA adduct. Method B gave values of TBA-reactive substances
      (TBARS) 2-fold higher than those detected with method A. SS lowered TBARS by
      about 50% with both methods, indicating a significant involvement of SA in plasma
      TBA reactivity. Standard SA, at a physiologically relevant concentration of 1.5
      mM, reacted with TBA, creating interference problems, which were substantially
      eliminated by SS plus correction for background absorbance. When method B was
      carried out in the lipid and protein fraction of plasma, SS inhibited by 65%
      TBARS formation only in the latter. Protein TBARS may be largely ascribed to SA
      containing glycoproteins and, to a minor extent, protein-bound MDA. Indeed, EDTA
      did not affect protein TBARS assessed in the presence of SS. TBA reactivity of
      whole plasma and of its lipid fraction was instead inhibited by EDTA, suggesting
      that lipoperoxides (and possibly monofunctional lipoperoxidation aldehydes) are
      involved as MDA precursors in the TBA test. Pretreatment of plasma with KI, a
      specific reductant of hydroperoxides, decreased TBARS by about 27%. Moreover,
      aspirin administration to humans to inhibit prostaglandin endoperoxide generation
      reduced plasma TBARS by 40%. In conclusion, reaction conditions affect the
      relationship between TBA reactivity and lipid peroxidation in human plasma. After
      correction for the interfering effects of SA in the TBA test, 40% of plasma TBARS
      appears related to in vivo generated prostaglandin endoperoxides and only about
      60% to lipoperoxidation products. Thus, the TBA test is not totally specific to
      oxidant-driven lipid peroxidation in human plasma.

PMID- 11461771
TI  - Measurement of 8-hydroxy-2'-deoxyadenosine in DNA by liquid chromatography/mass
      spectrometry.
AB  - 8-Hydroxyadenine (8-OH-Ade) is one of the major lesions, which is formed in DNA
      by hydroxyl radical attack on the C-8 position of adenine followed by oxidation.
      We describe the measurement of the nucleoside form of this compound, 8-hydroxy-2'
      deoxyadenosine (8-OH-dAdo) in DNA by liquid chromatography/mass spectrometry
      (LC/MS). The developed methodology enabled the separation by LC of 8-OH-dAdo from
      intact and modified nucleosides in enzymic hydrolysates of DNA. Measurements by
      MS were performed using atmospheric pressure ionization-electrospray process.
      Isotope-dilution MS was applied for quantification using a stable isotope-labeled
      analog of 8-OH-dAdo. The level of sensitivity of LC/MS with selected-ion
      monitoring (SIM) for 8-OH-dAdo amounted to approximately 10 femtomol of this
      compound on the LC column. This level of sensitivity is similar to that
      previously reported using LC-tandem MS (LC/MS/MS) with multiple-reaction
      monitoring mode (MRM) (7.5 femtomol). This compound was quantified in DNA at a
      level of approximately one molecule/10(6) DNA bases using amounts of DNA as low
      as 5 microg. The results suggested that this lesion may be quantified in DNA at
      even lower levels, when more DNA is used for analysis. In addition, gas
      chromatography/isotope-dilution mass spectrometry with SIM (GC/IDMS-SIM) was
      applied to measure 8-OH-Ade in DNA following its removal from DNA by acidic
      hydrolysis. The background levels of 8-OH-dAdo and 8-OH-Ade measured by LC/IDMS
      SIM and GC/IDMS-SIM, respectively, were nearly identical. In addition, DNA
      samples, which were exposed to ionizing radiation at different radiation doses,
      were analyzed by these techniques. Nearly identical results were obtained,
      indicating that both LC/IDMS-SIM and GC/IDMS-SIM can provide similar results. The
      level of sensitivity of GC/MS-SIM for 8-OH-Ade was also measured and found to be
      significantly greater than that of LC/MS-SIM and the reported sensitivity of
      LC/MS/MS-MRM for 8-OH-dAdo. The results show that the LC/MS technique is well
      suited for the measurement of 8-OH-dAdo in DNA.

PMID- 11461772
TI  - Influence of vitamin E and C supplementation on lipoprotein oxidation in patients
      with Alzheimer's disease.
AB  - Because increased oxidation is an important feature of Alzheimer's disease (AD)
      and low concentrations of antioxidant vitamins C and E have been observed in
      cerebrospinal fluid (CSF) of AD patients, supplementation with these antioxidants
      might delay the development of AD. Major targets for oxidation in brain are
      lipids and lipoproteins. We studied whether supplementation with antioxidative
      vitamins E and C can increase their concentrations not only in plasma but also in
      CSF, and as a consequence decrease the susceptibility of lipoproteins to in vitro
      oxidation. Two groups, each consisting of 10 patients with AD, were for 1 month
      supplemented daily with either a combination of 400 IU vitamin E and 1000 mg
      vitamin C, or 400 IU vitamin E alone. We found that supplementation with vitamin
      E and C significantly increased the concentrations of both vitamins in plasma and
      CSF. Importantly, the abnormally low concentrations of vitamin C were returned to
      normal level following treatment. As a consequence, susceptibility of CSF and
      plasma lipoproteins to in vitro oxidation was significantly decreased. In
      contrast, the supplementation with vitamin E alone significantly increased its
      CSF and plasma concentrations, but was unable to decrease the lipoprotein
      oxidizability. These findings document a superiority of a combined vitamin E + C
      supplementation over a vitamin E supplementation alone in AD and provide a
      biochemical basis for its use.

PMID- 11461773
TI  - NF-kappaB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori
      infection.
AB  - Oxygen radicals are considered as an important regulator in the pathogenesis of
      Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis.
      Inflammatory genes including inducible nitric oxide synthase (iNOS) may be
      regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF
      kappaB). iNOS induction has been related to gastric apoptosis. We studied the
      role of NF-kappaB on iNOS expression and apoptosis in H. pylori-stimulated
      gastric epithelial AGS cells. AGS cells were treated with antisense
      oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme
      catalase, an inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate
      (PDTC), iNOS inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME) and 2-amino
      5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite donor SIN-1, and a
      nitric oxide donor NOC-18 in the presence or absence of H. pylori. H. pylori
      induced cytotocixity time- and dose-dependently, which occurred with induction in
      iNOS expression and nitrite production. SIN-1 and NOC-18 induced dose-dependent
      cytotoxicity in AGS cells. Catalase, PDTC, L-NAME, and AMT prevented H. pylori
      induced cytotoxicity and apoptosis. It was related to their inhibition on iNOS
      expression and nitrite production. The cells treated with AS ODN had low levels
      of p50 and NF-kappaB and inhibited H. pylori-induced cytotoxicity, apoptosis,
      iNOS expression, and nitrite production. In conclusion, NF-kappaB plays a novel
      role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial
      cells.

PMID- 11461774
TI  - Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in
      fluoride-induced apoptosis in HL-60 cells.
AB  - It has been suggested that oxidative stress plays a major role in various forms
      of cell death, including necrosis and apoptosis. We have previously reported that
      fluoride (NaF) induces apoptosis in HL-60 cells by caspase-3 activation. The main
      focus of this investigation was to arrive at a possible pathway of the apoptosis
      induced by NaF upstream of caspase-3, because the mechanism is still unknown. The
      present study showed that after exposure to NaF, there was an increase in MDA and
      4-HNE and a loss of mitochondrial membrane potential (deltaPsi(m)) was also
      observed in NaF-treated cells. There was a significant increase in cytosolic
      cytochrome c, which is released from the mitochondria. We have reported a
      downregulation of Bcl-2 protein in NaF-treated cells. The antioxidants N-acetyl
      cysteine (NAC), glutathione (GSH) protected the cells from loss of deltaPsi(m),
      and there was no cytochrome c exit or Bcl-2 downregulation, and we suggest that
      these antioxidants prevent apoptosis induced by NaF. These results suggested that
      perhaps NaF induced apoptosis by oxidative stress-induced lipid peroxidation,
      causing loss of deltaPsi(m), and thereby releasing cytochrome c into the cytosol
      and further triggering the caspase cascade leading to apoptotic cell death in HL
      60 cells.

PMID- 11461775
TI  - Physiological amounts of ascorbate potentiate phorbol ester-induced nuclear
      binding of AP-1 transcription factor in cells of macrophagic lineage.
AB  - The aim of the reported research was to assess the potential modulatory effect
      exerted by physiological amounts of ascorbate complexed or not to iron on
      activator protein 1 (AP-1) nuclear binding. The metal-vitamin complex was shown
      able to strongly potentiate AP-1 binding as induced by phorbol 12-myristate 13
      acetate (PMA). Such enhancing activity by ascorbate was not observed on PMA
      dependent induction of another redox-sensitive transcription factor nuclear
      factor kappaB (NF-kappaB). Experiments performed in the presence of the metal
      chelator desferrioxamine (DFO) clearly indicated that ascorbate rather than iron
      was responsible for the potentiation of PMA effect. The composition of AP-1
      heterodimers revealed c-Jun, Jun D, and c-Fos as the major subunits upon PMA +/-
      ascorbate stimulation. The change in AP-1 components consequent to such stimuli
      was mainly dependent upon new synthesis. In fact, protein synthesis inhibitor
      cycloheximide (CHX) prevented the stimulation of AP-1 nuclear binding due to PMA
      and ascorbate plus PMA. Further, the vitamin was able to amplify the PMA
      dependent induction of p38 and pJNK. Thus, a fine modulation of critical thiols
      by the vitamin along the MAPK pathway is conceivable.

PMID- 11461776
TI  - Protein NMR spin trapping with [methyl-13C(3)]-MNP: application to the tyrosyl
      radical of equine myoglobin.
AB  - Direct spin trapping studies of protein radical adducts are limited as a
      consequence of the long rotational correlation times and consequent broadening of
      the ESR resonances. It can be difficult to determine both the nature and number
      of adduct species present. NMR detection of reduced spin adducts represents an
      alternate approach which, however, is subject to the limitations of lower
      sensitivity and a limited capability for isolating the resonances arising from
      the reduced adduct from other chemistry involving the spin trap. In the present
      study, we have utilized [methyl-13C(3)]-MNP for the detection and analysis of
      tyrosyl spin adducts formed as a result of exposure of equine myoglobin to
      hydrogen peroxide. The methyl-13C label allows high detection sensitivity in two
      dimensions, narrow line widths and most significantly, removal by dialysis of
      unreacted spin trap as well as any nonprotein derivatives that may form. For
      equine myoglobin, it is found that adduct formation involves a single residue-Tyr
      103 and further that adduct formation occurs at the C-3 carbon of the amino acid.
      HMQC-NOESY experiments further revealed the proximity of the labeled methyl
      groups to both the three aromatic tyrosyl protons as well as the aromatic protons
      of the nearby Phe-106 residue.

PMID- 11461777
TI  - 17beta-estradiol affects in vivo the low density lipoprotein composition,
      particle size, and oxidizability.
AB  - The aim of this study was to explore the possible modifications induced by 17beta
      estradiol (E(2)) in vivo on low-density lipoprotein (LDL) lipid composition,
      particle size, and oxidizability. For this purpose, women were recruited from an
      in vitro fertilization program, ranging their plasma E(2) levels from less than
      12 pg/ml to more than 2000 pg/ml at the end of the treatment. The LDL lipid
      constituents were analyzed by thin layer chromatography and image analysis, and
      the LDL diameter was calculated from the lipid data. The results showed that high
      plasma E(2) levels were associated with smaller LDL particles, with lower amounts
      of free and esterified cholesterol and an increased relative content of alpha
      tocopherol. The hormonal treatment produced a remodelation of the LDL acyl
      composition, rendering a lipoprotein enriched in saturated fatty acids, with a
      poorer polyunsaturated fatty acid content. These alterations in the
      physicochemical properties of LDL paralleled changes in the susceptibility of LDL
      to in vitro oxidation induced by both Cu(2+) and the peroxyl radical generator,
      2,2'-azobis (2-amidinopropane), these changes being mainly reflected in a reduced
      maximum oxidation rate. The in vivo changes in the physicochemical properties of
      LDL induced by E(2) could explain some of the antiatherogenic actions of
      estrogens.

PMID- 11461778
TI  - Carotenoids as scavengers of free radicals in a Fenton reaction: antioxidants or
      pro-oxidants?
AB  - The spin trapping EPR technique was used to study the influence of carotenoids
      (beta-carotene, 8'-apo-beta-caroten-8'-al, canthaxanthin, and ethyl 8'-apo-beta
      caroten-8'-oate) on the yield of free radicals in the Fenton reaction (Fe(2+) +
      H(2)O(2) --> Fe(3+) + .OH + -OH) in the organic solvents, DMSO, and methanol.
      DMPO and PBN were used as spin trapping agents. It was demonstrated that
      carotenoids could increase or decrease the total yield of free radicals depending
      on the oxidation potential of the carotenoids and the nature of the radicals. A
      reaction mechanism is suggested which includes the reduction of Fe(3+) to Fe(2+)
      by carotenoids. The effectiveness of this carotenoid-driven Fenton reaction
      increases with a decrease of the scavenging rates for free radicals and with
      decreasing oxidation potentials of carotenoids.

PMID- 11461779
TI  - Hypothermia enhances bcl-2 expression and protects against oxidative stress
      induced cell death in Chinese hamster ovary cells.
AB  - Oxidative stress is one of the major causes of cellular injury. Various reactive
      oxygen (ROS) and nitrogen (RNS) species such as superoxide, hydroxyl radical,
      peroxynitrite, and nitric oxide are involved in the manifestations of different
      types of organ toxicity and the resultant syndromes, symptoms, or diseases.
      Hypothermic conditions have been reported to reduce the oxidative stress in
      various in vitro and in vivo studies. In the present study, we sought to
      determine the effect of lowered temperatures on oxidative stress-induced cell
      death in Chinese hamster ovary (CHO) cells. We also investigated the oxidative
      stress-induced alterations in the expression of anti-apoptotic protein, bcl-2, in
      CHO cells at lowered temperatures. CHO cells were incubated at four different
      temperatures of 30, 32, 35, and 37 degrees C (control temperature) from 1 to 4 d.
      In another set, the cells were incubated with 100 microM hydrogen peroxide
      (H(2)O(2)) for 30 min before harvesting at different time points. The cells were
      harvested at 1, 2, 3, and 4 d. Cell survival was significantly higher at 30
      degrees C as compared to 37 degrees C over 4 d of incubation. In cells incubated
      with H(2)O(2), significantly higher cell viability was observed at lower
      temperatures as compared to the cells incubated at 37 degrees C. The activity of
      glutathione peroxidase (GSH-Px) also increased significantly at lower
      temperatures. Lowered temperature also provided a significant increase in the
      expression of anti-apoptotic protein, bcl-2 after 4 d of incubation. These data
      suggest that hypothermic conditions lowers the risk of oxidative stress-induced
      cellular damage and programmed cell death by increasing the activity of GSH-Px
      and by the induction in the expression of the anti-apoptotic protein, bcl-2.

PMID- 11461780
TI  - Iron inhibits the nitric oxide synthesis elicited by asbestos in murine
      macrophages.
AB  - Crocidolite fibers stimulated nitric oxide synthase (NOS) activity and expression
      in glial and alveolar murine macrophages: this effect was inhibited by iron
      supplementation and enhanced by iron chelation. We suggest that in these cells
      crocidolite stimulates NOS expression by decreasing the iron bioavailability and
      activating an iron-sensitive transcription factor.

PMID- 11461782
TI  - Do we need any more new antiepileptic drugs?
AB  - The last decade has seen the licensing of nine new antiepileptic drugs (AEDs)
      with more to come. Despite this, only 58 and 63% of patients with localisation
      related and newly diagnosed epilepsy, respectively, had been seizure-free for
      more than a year in separate prospective outcome studies undertaken at the
      Epilepsy Unit in Glasgow. Data will be presented to support the hypothesis that
      adolescent and adult epileptic patients comprise two distinct populations. Around
      60% will be controlled on monotherapy with the first or second choice AED, while
      the majority of the remainder is difficult-to-control. It is for this latter
      group and the many pharmacoresistant paediatric patients with encephalopathic
      syndromes that we need new AEDs. For a successful clinical outcome, patients must
      be able to tolerate the treatment. Neurotoxic, sedative, cognitive and
      psychiatric symptoms, dysmorphic and other long-term side effects, and
      teratogenesis plague the current crop of AEDs. Pharmacokinetic and
      pharmacodynamic interactions complicate the situation still further. These
      problems may, in part, be a consequence of combining drugs with similar
      mechanisms of action. Unravelling the genetics of the epilepsies will provide a
      range of tempting targets for pharmacological intervention. We need, also, models
      of refractory epilepsy to help identify promising therapies. An efficient
      regulatory trial programme will ensure rapid availability of new AEDs for the
      many children and adults whose lives continue to be blighted by seizures.

PMID- 11461783
TI  - Proof of principle trials: EEG surrogate endpoints.
AB  - Pivotal studies in man require prolonged administration to demonstrate efficacy
      for most seizure types. Earlier evidence of human efficacy can be of value for
      decision making, and EEG surrogate endpoints can be of value in this respect.
      Studies of spontaneous EEG discharges under standard recording conditions can
      demonstrate meaningful acute EEG effects of antiepileptic drugs (AEDs). These
      require a rapidly effective formulation of the product, preferably intravenous.
      The EEG recording conditions are standardised and the subject is required to
      perform a task to maintain a constant level of vigilance. The outcome measure of
      efficacy is spike count per minute or, if the discharges are more protracted (as
      generalised no spike and wave), the percentage of recording time occupied by
      discharges. Sub-acute experiments are conducted under less rigorously
      standardised conditions, but over longer periods, using ambulatory monitoring or
      telemetry to record the EEG. The photoparoxysmal responses (PPRs) of
      photosensitive subjects, evoked using a standardised stimulation protocol, are
      subject to less variability than spontaneous epileptiform activity. The PPR is
      elicited over a range of flash rates that can be used as a measure of
      sensitivity, and an effective treatment will reduce the range or abolish the PPR.
      Reduction in photosensitivity is demonstrable after a single dose of various
      AEDs, at clinically relevant plasma concentrations, even using drugs that are not
      generally effective for long-term treatment of photosensitive epilepsy. Evoked
      potential and nerve conduction studies and electronystagmography can be used to
      assess possible neurotoxicity, and quantitative EEG analysis can be employed to
      assess sedative effects.

PMID- 11461785
TI  - Proof of principle trials: exploratory open studies.
AB  - The aims of the observational, early phase IIa studies are usually several in
      number and often competing, and therefore the priorities should be clearly
      defined. The preclinical data, particularly the mode(s) of action of the drug and
      the results on experimental models, can help to build hypotheses on the agent's
      potential efficacy for individual seizure types and syndromes. For ethical
      reasons, the population selected for the initial clinical trials of antiepileptic
      drugs (AEDs) should be patients with continuing seizures (e.g. no less than two
      to four partial seizures/month) in spite of several therapeutic attempts using
      other appropriate AEDs, taken in monotherapy and in various combinations.
      Although the inherent bias in open, observational studies has limited their use
      in comparing treatments in epilepsy, they have several advantages over controlled
      trials, including lower cost, greater timeliness and inclusion of a broader range
      of patients. Observational, open studies with well-chosen patients and an
      adequate design tailored to answer precise predefined questions (including go/no
      go criteria) are most valuable for experienced clinicians in determining the
      clinical benefit of the drug, and for the pharmaceutical company in assessing the
      commercial merit of proceeding with further clinical testing.

PMID- 11461787
TI  - Proof of efficacy trials: choosing the dose.
AB  - It is apparent from current usage of antiepileptic drugs (AEDs) and from
      retrospective review of their drug development programmes, that the doses
      currently used in clinical practice differ from those which were used in clinical
      trials. This raises the question of how dose and titration schedules are selected
      in early development. An integral component of a drug development programme
      should be an assessment of dose response. The International Council on
      Harmonization of Technical Requirements for the Registration of Pharmaceuticals
      for Human Use [1994. Guidelines for industry: Dose-response information to
      support drug registration. ICH-E4. Federal Register] regulatory guidelines
      suggest that, at a minimum, three elements of dosing should be characterised: a
      maximum well tolerated dose, a minimum effective dose, and an appropriate rate of
      titration. Several specific designs can be utilised to assess dose response,
      which fall broadly into four categories, namely free titration, forced titration
      and dose escalation, parallel dose response, and dose reduction studies. In
      addition to these standard approaches, concentration-defined trials are an
      alternative in some circumstances and have been used with success in the
      development of newer AEDs. The designs chosen to address these elements are
      dependent upon the phase of development of the drug, and the severity of the
      disease, however, it is clear that conducting dose response studies earlier in
      the development programme may reduce the number of failed Phase 3 studies.

PMID- 11461789
TI  - Proof of efficacy trials: seizure types.
AB  - For proof of efficacy studies, ideally the seizure types included should also be
      the most common types of seizures so that an efficacy trial can recruit patients
      easily and in the shortest possible time frame, provide efficacy data that is
      valid for a large portion of the epilepsy population, include readily
      identifiable seizure types that are simple to count, and include seizures that
      occur frequently enough so that the trial can be short (3 months). Partial
      seizures are the most common seizure type in an adult population and therefore
      they represent the first choice for proof of efficacy studies, provided that data
      in experimental models support efficacy in this seizure type. Because there are
      already several antiepileptic drugs (AEDs) available which are effective for
      primary generalized seizure types, and patients with refractory primary
      generalized seizures are not so plentiful, and including these seizures as
      primary types to prove efficacy would be time consuming, expensive and therefore
      not feasible. It is concluded that, whereas proof of concept studies may include
      other seizure types, the first proof of efficacy studies should be undertaken in
      patients with frequent (>3/month) partial seizures.

PMID- 11461791
TI  - Seizure types and syndromes: lumping or splitting.
AB  - The efficacy of antiepileptic drugs (AEDs) is partly determined by the type of
      seizure being treated. Some seizure syndromes may be improved by certain drugs,
      whereas others may be worsened. Therefore, drug trials, which recruit patients
      with different types of epilepsy syndrome may fail to show a global therapeutic
      effect. In order to demonstrate an effect, it is necessary to use a design of
      trial, which gives optimum power, and this may involve identifying as homogeneous
      a group of patients as possible. This 'splitting' approach permits a reduction in
      the number of patients included in a trial. It also allows identification of
      syndromes, which may be paradoxically worsened by a drug. It is necessary to
      review from time to time the diagnostic criteria for particular syndromes,
      otherwise they may prove to be too restrictive. At some point of drug development
      a 'lumping' approach is necessary in order to include patients whose clinical
      characteristics challenge any classification.

PMID- 11461793
TI  - Proof of efficacy trials: cross-over versus parallel-group.
AB  - In recent years, most of the published trials of new antiepileptic drugs (AEDs)
      have had a parallel-group design rather than cross-over. Nevertheless, in some
      situations the cross-over trial does have advantages, and therefore, its role
      needs re-appraisal. The crossover design requires a much smaller number of
      patients for a similar statistical power because patients act as their own
      controls, which is a particular advantage when the type or severity of epilepsy
      varies widely in the patients recruited. As a result, the financial cost is
      smaller and fewer patients are exposed to the new agent, perhaps with ethical
      arguments in favour of this type of design in proof-of-efficacy trials. Within
      patient analysis also makes the detection of drug interactions more robust. On
      the other hand, there is a theoretical risk that the beneficial effects of the
      first treatment (or conversely, withdrawal seizures on stopping it) might carry
      over into the second treatment period and thereby confound the detection of
      treatment effects. The parallel-group design is more versatile in that a stable
      disease state is not a pre-requisite, and therefore, trials in newly diagnosed
      patients are possible. Multiple treatment limbs are also more practical. The
      duration of a parallel-group trial may be shorter because only one treatment
      period is involved, although this may be offset by the much larger number of
      patients needed to be recruited and the time involved in doing so. Parallel-group
      trials almost always require a multicentre approach, with the inevitable logistic
      problems involved. It is argued that proof-of-principle and add-on proof-of
      efficacy trials of a new drug are more efficiently undertaken using a cross-over
      design but that subsequent evaluation will require the versatility of trials with
      a parallel-group design.

PMID- 11461795
TI  - Proof of efficacy trials: endpoints.
AB  - Seizure frequency data are difficult to work with because they are so variable
      both between and within patients. Seizures can come in clusters, thereby adding
      to the variation in seizure frequency. Also, seizure frequency data are non
      parametric in nature, making them difficult to analyze by some statistical
      techniques without transforming them. Therefore, to improve data analysis in
      proof of efficacy studies, manipulations of seizure frequency are commonly used,
      such as the proportion of responders above an arbitrary threshold, or the
      response ratio. Other useful endpoints are time to nth seizure, number of seizure
      free days, proportion of seizure-free patients, and assessment of seizure
      severity using rating scales. The choice of endpoint(s) will depend upon the
      design of the study.

PMID- 11461797
TI  - Monotherapy trials: prerequisite data.
AB  - Is it possible for an antiepileptic drug (AED) to be effective as add-on therapy
      in refractory epilepsy but ineffective as monotherapy for the same seizure
      type(s)? If the answer is 'no', why not award a new AED a monotherapy licence
      once it has been shown to be effective as adjunctive treatment in placebo
      controlled, dose-ranging studies in patients with difficult-to-control epilepsy?
      The recent comparative study between carbamazepine and remacemide, however,
      suggests that subtle pharmacokinetic/pharmacodynamic interactions between
      established and new AEDs can indicate efficacy in add-on studies that does not
      necessarily transfer to monotherapy. There is some evidence that an AED whose
      primary mechanism of action does not involve blockade of voltage-dependent sodium
      channels may do less well than carbamazepine in terms of efficacy end-points in a
      double-blind, head-to-head comparison. These observations lead to the conclusion
      that monotherapy trials are, indeed, required. They should be undertaken after
      proof of efficacy has been obtained using a single short presurgical AED
      withdrawal study backed up by a substantive dose-ranging phase III efficacy
      trial. There is no reason to recommend earlier assessment since the clinical need
      for new AEDs is in refractory epilepsy. The subsequent monotherapy trial
      programme should contain elements utilising comparative and withdrawal designs.
      Sponsors should be able to seek a licence for their drug either as a first choice
      treatment in newly diagnosed epilepsy or as substitution monotherapy once
      treatment with at least one other AED has failed.

PMID- 11461799
TI  - Monotherapy trials: presurgical studies.
AB  - Presurgical evaluation of patients with refractory partial seizures provides a
      unique opportunity to perform a placebo-controlled, monotherapy trial. Some
      patients undergoing presurgical evaluations must have all of their antiepileptic
      drugs (AEDs) tapered in order to induce seizures and therefore such patients are
      possible candidates for a placebo-controlled monotherapy trial. Often, EEG
      monitoring is continued throughout the trial period, thus patients either
      receiving placebo or whose seizures do not completely respond to the active drug
      are still evaluated to determine whether or not surgery is feasible, supporting
      the validity of a trial in this setting. In addition, all patients are, in
      general, eligible to receive the study drug after the blinded period of the
      trial, and can therefore be assured of the possible therapeutic benefits of the
      study. Presurgical inpatients studies have been carried out using felbamate,
      gabapentin and oxcarbazepine. All patients randomised in these trials were
      refractory to previous treatment and the studies themselves were short-term and
      placebo-controlled. These presurgical studies are designed to elucidate AED
      activity and show statistically significant differences between active and
      control treatments during short-term therapy, and are therefore of use in
      fulfilling regulatory requirements. However, these measures of efficacy are
      distinctly different from those determined during chronic treatment and are
      therefore not necessarily predictive of clinical usefulness.

PMID- 11461801
TI  - Monotherapy trial design: conversion versus de novo.
AB  - It is difficult to design valid and well-controlled monotherapy trials that
      satisfy regulatory requirements and, at the same time, demonstrate the usefulness
      of a new drug in clinical practice. The conversion design is a drug-substitution
      trial in which patients with uncontrolled seizures are assigned to add-on
      treatment with an investigational drug and, usually, an appropriate control,
      after which pre-existing treatment is gradually discontinued. In the most
      utilised design, patients are randomised to receive a high dose versus low dose
      of the new drug, while concomitant medication is gradually discontinued. Exit
      criteria are predetermined to prevent excessive deterioration of seizures, and
      treatment retention time is used as the primary outcome variable to measure the
      effectiveness of the allocated treatments: the goal is to demonstrate higher
      retention rates in the high-dosage group. Conversion studies may help to fill
      some gaps in knowledge regarding efficacy and tolerability as monotherapy before
      larger-scale de-novo studies are started. In the de-novo design, newly diagnosed
      patients are randomised to receive the investigational drug or an active control.
      In equivalence (or non-inferiority) trials, the active control is usually an
      established antiepileptic drug (AED) such as carbamazepine or valproate, and
      outcome parameters may include proportion of patients achieving a predefined (for
      example, 6-month) seizure remission or the proportion of patients remaining in
      the trial (retention rate, a combined measure of efficacy and tolerability). In
      regulatory trials designed to show a difference, newly diagnosed patients are
      randomised to a high versus a low dose of the investigational drug, and exit
      criteria are again predetermined for patients whose seizures are not adequately
      controlled. In this case, outcome parameters may include time to first seizure in
      addition to retention in the trial. Comparative monotherapy trials in newly
      diagnosed patients are relevant to approximately 50% of the patients who develop
      epilepsy and can be satisfactorily managed with a single drug. These trials allow
      direct head-to-head comparisons and avoid the confounding effects of baseline
      drugs and co-medication withdrawal present in conversion studies. Long-term
      follow-up of patients who are receiving a drug in monotherapy at adequate doses
      gives the most clinically relevant answers regarding the usefulness of a new
      drug. It is concluded that the de-novo design is the gold standard when studying
      AEDs as monotherapy, but the conversion-to-monotherapy design can be used before
      starting the de-novo program in order to obtain estimates of efficacy and
      tolerability of the AED as monotherapy in a population of difficult-to-treat
      patients. With both designs, the use of suboptimal comparators incorporated into
      some of the regulatory trials is a cause of ethical concern.

PMID- 11461803
TI  - Monotherapy trials: sequential design.
AB  - In a sequential clinical trial, the accumulating data are subjected to a series
      of interim analyses, each of which involves a comparison of the treatments under
      study in respect of the primary efficacy criterion. The trial is stopped as soon
      as it is evident that one treatment is superior to the other, or that no such
      difference is going to be found. The stopping rule is devised to ensure that the
      required significance level and power are achieved and that valid statistical
      inference can be drawn at the end of the study. The methodology will be presented
      by means of a case study. This is the SEReNE study, which was completed last year
      and compared remacemide with carbamazepine in the treatment of newly diagnosed
      epilepsy. The study employed a double triangular test: an efficient form of
      sequential design for the comparison of two active treatments. The primary
      efficacy response was time from randomisation to the first seizure following dose
      titration. Details will be given of the stopping rule employed, the number of
      patients forecasted, the progress of the trial and its final analysis. The
      procedure adopted will be reviewed, and its suitability for future trials
      assessed.

PMID- 11461805
TI  - Monotherapy comparative trials: placebos and suboptimal comparators.
AB  - The superiority of a drug can be demonstrated using several comparative designs
      against either placebo, or a low dose of the study drug or standard anti
      epileptic drug (AED). Firstly, the population could consist of inpatients
      admitted for presurgical monitoring. Although these trials are scientifically
      interpretable, and involve direct comparison of the study drug against placebo,
      they are, in general, too short in duration to be able to define clinical
      relevance. Secondly, patients with refractory epilepsy can participate in
      monotherapy substitution studies during which patients are randomised to one of
      at least two arms with the baseline AED subsequently tapered and discontinued.
      These patients are maintained on monotherapy for the rest of the trial. An
      enriched design can also be used in which patients successfully converted to a
      high dose of the study drug, are then randomised to either the high or low dose
      of the treatment. The ethics of such enriched designs is questionable. More
      recently, studies have been carried out in patients with new onset seizures. In
      such designs, patients are randomised to the study drug (possibly at different
      dosages), versus a placebo or pseudo-placebo control. Comparative trials in
      patients with newly-diagnosed epilepsy makes it more difficult to obtain
      significant differences due to the high number of patients needed and the usually
      lengthy time course of the study.

PMID- 11461807
TI  - Monotherapy comparative trials: equivalence and differences in clinical trials.
AB  - Investigators are familiar with the concept of clinical trial design to detect
      differences. Equivalence studies set out to define how similar treatments might
      be. They become important for two reasons: (1) similarities may be as clinically
      important as differences and (2) in therapeutic areas with drugs of proven
      efficacy already marketed, it may be ethically difficult to perform placebo
      control studies. If equivalence is rigorously defined (the minimal clinically
      important difference), they could represent a route to licensing (cancer
      chemotherapy and antibiotics). Equivalence will be defined by the limits of 95%
      confidence intervals for a comparison being constrained within pre-defined
      limits. As such, studies need larger numbers of subjects rather than difference
      studies, and intention-to-treat analysis may no longer be the more conservative
      approach.

PMID- 11461809
TI  - Monotherapy trials: endpoints.
AB  - Monotherapy antiepileptic drug (AED) trials can optimally provide information
      concerning efficacy and tolerability of one drug compared with placebo, as well
      as to different doses or rates of administration. Commonly, a drug is compared
      with one or more other drugs. The outcome measures will be dictated by the
      questions being asked. In most comparative studies, the single overall result
      that best defines success or failure is time of continuation on drug as expressed
      in a life table. Discontinuation before planned completion of the study implies
      insufficient efficacy or unacceptable adverse effects. A statistically
      significant difference between treatments provides important support for
      recommending the drug or dose with the best outcome. The criteria for
      continuation/discontinuation are defined in the design based on the expected
      outcome. The outcome of primary importance is efficacy in prevention of seizures
      or a decrease in severity. Complete control for the duration of the study is the
      ultimate goal but in some populations may not be possible. The number of subjects
      entering remission gives further information about long term outcome. Time to
      first (nth) seizure provides similar evidence of efficacy. Seizure rates allow
      comparisons of subjects retained for different lengths of time in the trial.
      Differences in seizure severity may be of clinical importance and multiple
      efforts have been made to develop instruments to accurately measure this outcome.
      Adverse effects of the drugs are the second major outcome. These can be expressed
      as incidence and/or prevalence. The presence and frequency of side effects will
      depend on how the study is designed and whether these effects are specifically
      sought by the investigators. Serious systemic safety outcomes are monitored, but
      the relative infrequency of occurrence and number of subjects in the trials
      usually do not provide enough power to detect statistically significant
      differences except for rash. Tolerability is more easily documented but is
      difficult to access accurately in the absence of placebo controls. Frequency,
      severity and persistence are measurable. Specific unwanted types of drug effects
      can be specifically studied using detailed neuropsychological test batteries.
      Some information concerning pharmacokinetic properties may be obtained but are
      better assessed in other types of trials. A final important outcome is the effect
      of drug therapy on quality of life. Although a favorable finding in this outcome
      is most desirable, the measures used are much less precise than those for
      efficacy and adverse effects.

PMID- 11461812
TI  - Trial duration and follow-up.
AB  - The chronic nature of most seizure disorders requires that antiepileptic drugs
      (AEDs) be administered for many years. Therefore, new drugs should be evaluated
      over a period sufficient to assess potential development of tolerance as well as
      long-term safety. While patients and prescribers desire extensive long-term data
      prior to registration, too stringent requirements would discourage industry's
      investment into new treatments, and a compromise between these stakes should be
      sought. In add-on studies, it is recommended that patients completing double
      blind assessment be offered indefinite open-label treatment, and that safety data
      be collected prospectively. Monotherapy trials in refractory patients include
      presurgical and conversion to monotherapy studies. Duration of assessment in
      these studies rarely exceeds few weeks, and endpoints relate to seizure
      deterioration rather than improvement; this surrogate measure of efficacy is not
      necessarily predictive of clinical usefulness and, in view of ethical concerns,
      the rationale for these studies should be questioned. There may be scope,
      however, for alternative study designs whereby refractory patients are converted
      to monotherapy and followed up for several months. Active-control long-term
      monotherapy trials in newly diagnosed patients represent the mainstay for
      evaluating efficacy and safety. In patients with partial or generalized tonic
      clonic seizures, most trials conducted to date had a duration of 6-12 months, but
      this period may be insufficient to assess seizure freedom rates at optimized
      dosages, and at least one 2-year trial would be desirable. With respect to open
      label follow-up, many protocols require that the randomization code not be broken
      until the database has been sealed. Patients completing blind assessment are
      often forced through unblinding procedures which involve tapering of trial
      medication and institution of an open-label therapy which may differ, in dosage
      or type of medication, from that taken previously. In view of ethical concerns,
      the rationale for this practice should also be questioned.

PMID- 11461814
TI  - Trials in children.
AB  - Over 20% of epilepsies in children are intractable, and are frequently associated
      with deterioration of motor and cognitive functions. Some are similar to those
      seen in adults, but many age-related epilepsies occur only in children.
      Therefore, a sizeable proportion of intractable epilepsies of childhood are
      different from those encountered in adults, and there is an urgent need for
      antiepileptic drug trials to be undertaken in children at an early stage of
      development. An ethical framework within which these trials can be conducted has
      been defined.

PMID- 11461817
TI  - Trials in women.
AB  - Women of childbearing age have been viewed as a 'vulnerable population' and have
      been systematically excluded from early clinical trials. A change in attitude and
      policies occurred in the last decade, with a consequent increase of women
      participating in clinical trials. The implications are increasing respect for the
      woman's capacity to make her own risk-benefit choices, early evaluation of
      patients that represent the ultimate user of a drug and equal opportunities for
      women to benefit from the therapeutic potential of new drugs. Drug trials should
      be designed to identify sex-related effects and to analyse the efficacy and
      tolerability of antiepileptic drugs (AEDs) by gender. Further aspects should be
      considered, including changes in response in relation to the menstrual cycle and
      over the various stages of reproductive life; interactions between hormonal
      therapies and AEDs; the effect of AEDs on reproductive function and possible
      consequences of prenatal exposure to AEDs. These considerations become even more
      critical when pregnant and lactating women are considered, since any risk for the
      offspring is unacceptable unless drug administration is likely to have major
      medical benefits for the mother.

PMID- 11461819
TI  - Trials in the elderly.
AB  - Epilepsy in the elderly differs from that in younger people in several respects.
      The incidence of seizures increases sharply with age and the seizures are more
      often symptomatic of underlying brain disease. The handling of antiepileptic
      drugs (AEDs) may be impaired by diminishing hepatic and renal function as age
      advances, and the pharmacodynamic response to drug therapy may be altered. In
      consequence, the elderly are more likely to experience adverse drug effects.
      Whether their seizures respond to drug treatment in a different way from younger
      patients is uncertain, but there are, nevertheless, convincing arguments for
      clinical trials being undertaken specifically in this population during the Phase
      II/IV development programme.

PMID- 11461821
TI  - Cognitive and behavioural assessment in clinical trials: when should they be
      done?
AB  - The issue of 'timing' of behavioural assessments in clinical trials can be
      approached in two different ways. Firstly the 'timing' during the process of drug
      development. As a rule, cognitive and behavioural side effects of antiepileptic
      drug treatment do not become an issue until the drug is marketed. At this stage a
      negative result has large marketing effects and this leads to a tendency to
      organise 'positive studies'('no-effect results'), that can be achieved by
      reducing power. A second approach is the 'timing' of cognitive assessment during
      a trial. The first and intuitive answer to the question 'when this should be
      done' is to perform assessments during an untreated baseline that is then
      compared with an endpoint during antiepileptic drug (AED) treatment. This is the
      'gold standard design' for cognitive assessments in the majority of the cognitive
      trials. However, in patients with epilepsy, the behavioural drug effects are not
      independent from the effect of the epilepsy or the seizures. Recent studies have
      confirmed that the effect of uncontrolled seizures are often larger than the
      effects of drug treatment, leading to the so-called seizure confound, that is,
      adverse cognitive AED effects may be masked by beneficial effects of better
      seizure control. In such studies endpoint scores are thus improved, hiding
      possible negative drug effects. Other designs may have other limitations: e.g. in
      using adjunctive therapy the identification of the components of a treatment most
      responsible for any observed effects presents a difficult problem; in normal
      volunteers, exposure durations which are not representative of those in epilepsy
      patients on chronic treatment represent a major validity issue. We therefore
      consider the drug withdrawal study as the optimal design for assessing
      behavioural drug effects. In this design subjects are tested while still on
      medication and after withdrawal; larger gains in the epilepsy group relative to
      the controls are considered evidence for a reversible impairment, attributable to
      AED use.

PMID- 11461823
TI  - Cognitive and behavioural assessments in clinical trials: what type of measure?
AB  - This paper provides an overview of the types of neuropsychological and
      behavioural measures used in randomised controlled trials (RCTS) of antiepileptic
      drugs (AEDs) in patients with epilepsy. The results of previous systematic
      reviews are reported in respect of the methods used in clinical trials to assess
      cognitive and behavioural effects of AED treatment. There were 46 trials
      incorporating behavioural measures and 40 trials incorporating neuropsychological
      measures. The evidence supporting the choice of test, and their reliability,
      validity, and sensitivity to change was minimal. It is concluded that poor
      reporting of methods and a plethora of both neuropsychological and behavioural
      measures make it difficult to provide any meaningful comments about the effects
      of AED treatment. A much more standardised approach to assessing these effects is
      necessary.

PMID- 11461825
TI  - Assessment of teratogenic risk.
AB  - Although the association between prenatal exposure to old generation
      antiepileptic drugs (AEDs) and major congenital malformations has been studied
      for many years, it is not clear whether any specific AED, or AED combination, is
      more harmful than others, or whether any pattern of malformations can be
      considered specific for any given drug. Relationships between dosage and plasma
      concentrations of AEDs and the risk of malformations also need to be clarified.
      The greatest limitation of all studies performed to date is the fact that none
      included a sufficiently large number of pregnancies. For newer generation AEDs
      the teratogenic risk, if any, is unknown. Large prospective studies are needed.
      The best approach is the establishment of registries through international
      collaboration. Inclusion of non-epileptic controls and untreated women is not
      strictly necessary to evaluate the comparative teratogenic risk of AEDs. The
      modalities of data collection should be pre-defined; common protocols,
      sufficiently exhaustive but at the same time easy to perform, should be shared
      from the beginning. Information on the presence or absence of major malformations
      or prenatal growth retardation, and on all major factors that may affect the
      teratogenic endpoints should be obtained. Study designs should ensure high
      quality data recording, and adequate quality assurance and auditing procedures.
      Further requisites are a clear definition of congenital malformation and
      prolonged follow-up to detect the occurrence of congenital malformations not
      detected at birth.

PMID- 11461827
TI  - Structure of TrwB, a gatekeeper in bacterial conjugation.
AB  - Bacterial conjugation implies a trans-membrane passage of DNA, mediated by
      proteins encoded in conjugative plasmids. This results in a spread of genetic
      information, including antibiotic resistance acquisition by pathogens. Special
      cases of conjugation are trans-kingdom gene transfer from bacteria to plants or
      fungi, and even bacterial sporulation and cell division. One of the main actors
      in this process is an integral inner membrane DNA-binding protein, called TrwB in
      the E. coli R388 conjugative system. It is responsible for coupling the single
      strand DNA to be transferred from the donor to the acceptor cell in its complex
      with other proteins, with a type IV secretion system making up the mating
      apparatus. The TrwB protomer consists of two domains: a nucleotide-binding domain
      of alpha/beta topology, similar to RecA and DNA ring helicases, and an all-alpha
      domain. The quaternary structure reveals an almost spherical homohexamer,
      strikingly similar to F(1)-ATPase. A central 20 A wide channel traverses the
      hexamer, thus connecting cytoplasm with periplasm.

PMID- 11461828
TI  - Macromolecular crowding and its role as intracellular signalling of cell volume
      regulation.
AB  - Macromolecular crowding has been proposed as a mechanism by means of which a cell
      can sense relatively small changes in volume or, more accurately, the
      concentration of intracellular solutes. According to the macromolecular theory,
      the kinetics and equilibria of enzymes can be greatly influenced by small changes
      in the concentration of ambient, inert macromolecules. A 10% change in the
      concentration of intracellular proteins can lead to changes of up to a factor of
      ten in the thermodynamic activity of putative molecular regulatory species, and
      consequently, the extent to which such regulator(s) may bind to and activate
      membrane-associated ion transporters. The aim of this review is to examine the
      concept of macromolecular crowding and how it profoundly affects macromolecular
      association in an intact cell with particular emphasis on its implication as a
      sensor and a mechanism through which cell volume is regulated.

PMID- 11461829
TI  - Ligand specificity and conformational stability of human fatty acid-binding
      proteins.
AB  - Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually
      identical backbone structures that facilitate the solubility and intracellular
      transport of fatty acids. At least eight different types of FABP occur, each with
      a specific tissue distribution and possibly with a distinct function. To define
      the functional characteristics of all eight human FABPs, viz. heart (H), brain
      (B), myelin (M), adipocyte (A), epidermal (E), intestinal (I), liver (L) and
      ileal lipid-binding protein (I-LBP), we studied their ligand specificity, their
      conformational stability and their immunological crossreactivity. Additionally,
      binding of bile acids to I-LBP was studied. The FABP types showed differences in
      fatty acid binding affinity. Generally, the affinity for palmitic acid was lower
      than for oleic and arachidonic acid. All FABP types, except E-FABP, I-FABP and I
      LBP interacted with 1-anilinonaphtalene-8-sulphonic acid (ANS). Only L-FABP, I
      FABP and M-FABP showed binding of 11-((5-dimethylaminonaphtalene-1
      sulfonyl)amino)undecanoic acid (DAUDA). I-LBP showed increasing binding of bile
      acids in the order taurine-conjugated>glycine-conjugated>unconjugated bile acids.
      A hydroxylgroup of bile acids at position 7 decreased and at position 12
      increased the binding affinity to I-LBP. The fatty acid-binding affinity and the
      conformation of FABP types were differentially affected in the presence of urea.
      Our results demonstrate significant differences in ligand binding, conformational
      stability and surface properties between different FABP types which may point to
      a specific function in certain cells and tissues. The preference of I-LBP (but
      not L-FABP) for conjugated bile acids is in accordance with a specific role in
      bile acid reabsorption in the ileum.

PMID- 11461830
TI  - Effects of chemical modifications of crotoxin B, the phospholipase A(2) subunit
      of crotoxin from Crotalus durissus terrificus snake venom, on its enzymatic and
      pharmacological activities.
AB  - Crotoxin B, the basic Asp49-PLA(2) subunit from crotoxin, the main component of
      Crotalus durissus terrificus venom, displays myotoxic, edema-inducing,
      bactericidal (upon Escherichia coli), liposomal-disrupting and anticoagulant
      activities. Chemical modifications of His (with 4-bromophenacyl bromide, BPB),
      Tyr (with 2-nitrobenzenesulphonyl fluoride, NBSF), Trp (with o
      nitrophenylsulphenyl chloride, NPSC) and Lys (with acetic anhydride) residues of
      this protein, in addition to cleavage with cyanogen bromide (CNBr) and inhibition
      with ethylenediaminetetraacetic acid (EDTA), were carried out in order to study
      their effects on enzymatic and pharmacological activities. Lethality was reduced
      after modification of His or Lys residues, as well as after cleavage with CNBr,
      while enzymatic activity was completely abolished after modification of His or
      incubation with EDTA. Modification of Lys or Tyr, or cleavage with CNBr,
      partially reduced enzymatic activity. Anticoagulant activity was modified
      similarly to enzymatic activity, evidencing the dependency of this
      pharmacological effect on catalytic activity. Myotoxicity was reduced after
      modification of His or Lys, as well as after cleavage with CNBr, whereas EDTA
      reduced this effect to a lesser extent. Bactericidal effect was significantly
      reduced only after modification of Lys and after cleavage with CNBr. Edema
      inducing activity was partially inhibited after treatment with EDTA and strongly
      reduced after acetylation of Lys residues and cleavage with CNBr, being only
      partially reduced after His alkylation. On the other hand, liposome disrupting
      activity was only partially reduced after modification of His and Tyr or after
      cleavage with CNBr. Modification of Trp residue partially reduced lethality and
      myotoxicity but did not affect enzymatic or anticoagulant activities. These data
      indicate that enzymatic activity is relevant for some pharmacological effects
      induced by crotoxin B (mainly lethal, myotoxic and anticoagulant activities), and
      also evidence that this subunit of crotoxin displays regions different from the
      active catalytic site which are involved in some of the toxic and pharmacological
      effects induced by this phospholipase A(2).

PMID- 11461831
TI  - Properties of porcine white adipose tissue and liver mitochondrial
      subpopulations.
AB  - Properties of porcine white adipose tissue heavy and light mitochondrial
      subpopulations were investigated so as to identify any functional heterogeneity.
      Liver mitochondrial subpopulations were concurrently evaluated since their
      properties have been studied in some detail. Mitochondrial subpopulations were
      isolated by means of differential centrifugation and the relative purity
      estimated using marker enzymes. Due to the greater contamination of the light
      mitochondrial fractions, mtDNA content, determined by PCR analysis, was used as a
      basis to demonstrate any mitochondrial heterogeneity. Enzymatic activity,
      electron microscopy, lipid analysis and Western blotting were used to
      characterise the different populations. With the exception of liver cytochrome c
      oxidase, the enzymatic capacity of adipose and liver heavy mitochondria ranged
      between approximately two- and threefold higher than the corresponding light
      fraction. The cardiolipin content and mean mitochondrial diameters paralleled
      these differences, suggesting an increased mitochondrial mass rather than a
      functional difference. However, the cytochrome c oxidase activity of the liver
      heavy mitochondria was 4.75-fold higher relative to the light fraction. A strong
      correlation between cytochrome c oxidase activity and the subunit I content was
      evident. Adipose tissue mitochondrial subpopulations would seem to possess a
      comparable oxidative capacity per gram mitochondrial protein, while liver heavy
      mitochondria possess an increased oxidative capacity and mass.

PMID- 11461832
TI  - Human dihydrolipoamide dehydrogenase gene transcription is mediated by cAMP
      response element-like site and TACGAC direct repeat.
AB  - Dihydrolipoamide dehydrogenase is a common component of four multienzyme
      complexes which are involved in oxidation of carbohydrates, lipids and amino
      acids. To better understand the regulation of human DLD gene expression, we have
      analyzed the proximal promoter region of this gene. DNase I footprinting analysis
      of the promoter region (-322 to +47 bp) revealed four major protein-binding
      domains (termed P1-P4). Nested deletions and site-specific mutations of
      approximately 100 bp proximal promoter region identified two elements, TACGAC
      direct repeat sequence and cAMP-response element (CRE)-like site, which are
      localized in the P2 and P1 domains, respectively, and mediate basal transcription
      of the DLD gene. Electrophoretic mobility supershift assays showed that the CRE
      like site is associated with CRE binding protein. Interestingly, when DLD
      promoter constructs (-1.8 kb to +47 bp and -78 to +47 bp) fused with the
      chloramphenicol acetyltransferase (CAT) reporter gene were transiently
      transfected into human HepG2 cells either in the presence or absence of 0.5 mM 8
      Br-cAMP, the levels of CAT expression remained unaffected. In addition,
      endogenous DLD mRNA levels in HepG2 cells also remained unaffected by treatment
      with 0.5 mM 8-Br-cAMP. These results indicate that the CRE binding protein is
      essential for basal transcription of the human DLD promoter, but does not confer
      cAMP-dependent gene regulation.

PMID- 11461833
TI  - Beyond the locus control region: new light on beta-globin locus regulation.
AB  - The locus control region (LCR) is a novel class of cis-acting regulatory
      sequences that enable high-level, tissue-specific, copy number-dependent, and
      chromosomal position-independent gene expression in transgenic mice. Recent
      studies on endogenous beta-globin locus and other loci have offered new insights
      either in support of or in contrast to our knowledge of the relationship between
      chromatin conformation and transcriptional regulation, the long-distance
      interaction between enhancers and promoters, and the developmental switching of
      multiple-gene loci. Our perceptions of the regulatory roles for LCR and elements
      beyond the LCR in beta-globin locus regulation have been challenged and demand re
      evaluation. A sound elucidation of gene regulation mechanisms may rely on a fine
      understanding of functional interplay between cis-acting elements and trans
      acting factors that participate in gene silencing and activation in their native
      genomic, cellular, and developmental state.

PMID- 11461834
TI  - Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to
      function.
AB  - The detection of isolated heart block in utero strongly predicts the presence of
      maternal autoantibodies reactive with 52 kDa SSA/Ro. The mechanisms that underlie
      this observation may be elucidated by defining the function of the target
      antigen. The initial approach was to identify proteins interactive with 52Ro
      using transcriptional activity in the yeast 2-hybrid system. A cDNA library was
      constructed using RNA isolated from human fetal hearts (12-23 weeks) and cloned
      into the HybriZAP vector encoding the activation domain of GAL4(AD) as target.
      Approximately 7 x 10(6) cDNAs were cotransformed with the bait into YRG-2.
      Plasmids from five interactive colonies were sequenced and three identified as
      the specific human deubiquitinating enzyme, UnpEL. UnpEL did not interact with
      bait plasmid encoding 52 beta, an alternative leucine zipper-minus form of 52 kDa
      SSA/Ro which is maximally expressed in fetal life. The mammalian 2-hybrid assay
      confirmed the interaction between full-length 52Ro and UnpEL. Further support for
      a biologic interaction was the marked redistribution in cellular localization of
      UnpEL following cotransfection of the two proteins into cultured human
      cardiocytes, human renal carcinoma cells (293 cells), and monkey kidney
      fibroblasts (COS-1). In conclusion, the interaction of full-length 52Ro and UnpEL
      implies that the former may also be involved in the ubiquitin pathway, an
      observation of particular interest since 52Ro contains a RING finger domain, a
      motif common to several recently reported proteins involved in modulating
      ubiquitination. The absence of an interaction with 52 beta raises the
      consideration that regulation of protein ubiquitination might differ in fetal
      life.

PMID- 11461835
TI  - Ribonucleases and their antitumor activity.
AB  - The antitumor effect of ribonucleases was studied with animal ribonucleolytic
      enzymes, bovine pancreatic RNase A, bovine seminal RNase (BS-RNase), onconase and
      angiogenin. While bovine pancreatic RNase A exerts a minor antitumor effect, BS
      RNase and onconase exert significant effects. Angiogenin, as RNase, works in an
      opposite way, it initiates vascularization of tumors and subsequent tumor growth.
      Ribonunclease inhibitors are not able to inhibit the antitumor effectiveness of
      BS-RNase or onconase. However, they do so in the case of pancreatic RNases.
      Conjugation of BS-RNase with antibodies against tumor antigens (preparation of
      immunotoxins) like the conjugation of the enzyme with polymers enhances the
      antitumor activity of the ribonuclease. After conjugation with polymers, the half
      life of BS-RNase in blood is extended and its immunogenicity reduced. Recombinant
      RNases have the same functional activity as the native enzymes. The synthetic
      genes have also been modified, some of them with gene sequences typical for the
      BS-RNase parts. Recent experimental efforts are directed to the preparation of
      'humanized antitumor ribonuclease' that would be structurally similar to human
      enzyme with minimal immunogenicity and side effects. The angiogenesis of tumors
      is attempted to be minimized by specific antibodies or anti-angiogenic
      substances.

PMID- 11461836
TI  - Comparison of metallothionein concentrations and tissue distribution of trace
      metals in crabs (Pachygrapsus marmoratus) from a metal-rich estuary, in and out
      of the reproductive season.
AB  - Crabs, Pachygrapsus marmoratus, were sampled in June 1997 and February 1998 from
      two sites (at the mouth and 25 km upstream) in the metal-rich Gironde estuary,
      France. Gills and hepatopancreas were analysed for metal (Cd, Cu, Zn) and
      metallothionein (MT) contents, in order to examine the influence of both
      biological and environmental factors on the physico-chemical forms of detoxified
      metal storage in the crabs. The concentrations of MT and both cytosolic and
      insoluble metals were not greatly different between males and females, and the
      influence of organ weights was also minimal. Intersite differences were observed,
      probably resulting from the gradient of salinity in the estuary, which interacts
      with both the chemical speciation and bioavailability of metals, and the general
      protein metabolism of the crabs. Seasonal changes were also important, probably
      in interaction with the moult and reproductive cycles. In February,
      concentrations of insoluble metals were generally higher than in June, in both
      organs, suggesting that essential metals, particularly Zn, are stored during
      winter then remobilised during the breeding season. The natural variability in
      the concentrations of MT often concealed any relationship with accumulated metal
      concentrations. Thus MT in crabs cannot be considered as a useful biomarker of
      metal pollution.

PMID- 11461837
TI  - Importance of sulfate, cysteine and methionine as precursors to felinine
      synthesis by domestic cats (Felis catus).
AB  - There is conflicting evidence in the literature on the utilization of cysteine
      and methionine as precursors to the urinary sulfur-containing amino acid felinine
      in cats. Three entire domestic short-haired male cats, housed individually in
      metabolism cages, were injected intraperitoneally with either [35S]-sulfate,
      [35S]-cysteine, or [35S]-methionine. Daily urine samples were collected
      quantitatively for up to 9 days after injection. Each cat was injected once with
      each compound after observing an appropriate interval for [35S] to be depleted
      between injections. All the urine samples were analysed for felinine content and
      total radioactivity. Felinine was isolated from each urine sample and analysed
      for radioactivity. No radioactivity was found in felinine from cats injected with
      [35S]-sulfate. The mean (+/-S.E.M.) cumulative recovery of radioactivity in the
      urine of the [35S]-sulfate injected cats was 90.6+/-6.1% after 4 days. The mean
      (+/-S.E.M.) cumulative incorporation rate of radioactivity into felinine by the
      cats receiving the [35S]-cysteine and [35S]-methionine were 11.6+/-1.6 and 8.6+/
      0.6%, respectively, after 9 days. The mean (+/-S.E.M.) cumulative recoveries of
      radioactivity in the urine were 58.1+/-3.7 and 36.0+/-8.0%, respectively.
      Cysteine and methionine, but not sulfate, are precursors to felinine, with
      cysteine being a more quantitatively important precursor compared to methionine.

PMID- 11461838
TI  - Development and validation of a homologous zebrafish (Danio rerio Hamilton
      Buchanan) vitellogenin enzyme-linked immunosorbent assay (ELISA) and its
      application for studies on estrogenic chemicals.
AB  - Vitellogenin (VTG) was isolated by anion exchange chromatography from plasma of
      female zebrafish (Danio rerio) induced with 17alpha-ethinylestradiol (EE2). The
      purity of the VTG isolate was confirmed by polyacrylamide gel electrophoresis
      (SDS-PAGE). Purified VTG was used to raise polyclonal antibodies in rabbits and
      the specificity of the antisera for VTG confirmed by Western blot analysis of
      plasma proteins separated by SDS-PAGE. The antibodies cross-reacted with two
      proteins in the plasma of female zebrafish, with molecular masses of
      approximately 142 and 171 kDa. No cross-reactivity was observed with any other
      plasma proteins. A competitive enzyme-linked immunosorbent assay (ELISA) was
      developed using the polyclonal zebrafish VTG (z-VTG) antibodies and purified z
      VTG as ligand and standard, respectively. The z-VTG ELISA was sensitive with a
      detection limit of between 2.0 and 3.0 ng purified VTG/ml, and a working range
      between 3 and 500 ng/ml (30-85% binding). The ELISA demonstrated precision, with
      inter- and intra-assay variations of 7.5+/-2.7 and 4.9+/-1.4%, respectively.
      Plasma from adult zebrafish and whole body homogenates from juvenile zebrafish
      diluted parallel with the z-VTG standard in the ELISA, validating the assay for
      quantifying z-VTG in both of these tissues. Exposure of adult male zebrafish to
      EE2 via water induced a concentration-dependent induction of VTG with a lowest
      observed effect concentration (LOEC) < or =1.67 ng EE2/l (for a 21-day exposure).
      The homologous z-VTG ELISA provides a valuable tool for the study of
      environmental estrogens in zebrafish.

PMID- 11461839
TI  - Comparison of reproductive parameters in male yellow-blotched map turtles
      (Graptemys flavimaculata) from a historically contaminated site and a reference
      site.
AB  - From May to September of 1998, we collected monthly plasma samples from male
      yellow-blotched map turtles captured at two sites in the Pascagoula River
      drainage, Mississippi. One site (Vancleave) has a documented history of pollution
      from industrial sources (principally 2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD).
      Fish consumption advisories at the Vancleave site were lifted in 1996 and current
      impacts appear minimal. However, the yellow-blotched map turtle, a federally
      protected species, continues to decline in numbers. To determine if endocrine
      disruption could be a factor in the low reproductive rates observed in Vancleave
      turtles, we examined levels of plasma testosterone (T) and estradiol-17beta
      (E(2)) from males at this site and a second site (Leaksville), which has no known
      source of industrial pollution. Plasma was also tested for vitellogenin (VTG),
      which, in males, can be a biomarker of exposure to estrogenic contaminants. No
      males had detectable plasma VTG nor did mean monthly E(2) levels differ between
      sites. However, 10% of males from the historically polluted site were found to
      have high levels of E(2) (equivalent to levels found in females) and T was
      significantly lower for males captured at this site for 3 of 5 months. Our data
      suggest that the current impact of contaminants on reproduction in this
      population is limited. However, a portion of the population may have been
      affected developmentally, as represented by differences in reproductive
      parameters detected between sites.

PMID- 11461840
TI  - Persistent organochlorine pesticides detected in blood and tissue samples of
      vultures from different localities in South Africa.
AB  - Gas chromatography was used to establish the presence of quantifiable residues of
      14 persistent chlorinated hydrocarbon pollutants in whole blood, clotted blood,
      heart, kidney, liver and muscle samples obtained from individual African
      whitebacked (Pseudogyps africanus), Cape griffon (Gyps coprotheres) and
      Lappetfaced (Torgos tracheliotos) vultures from different localities in South
      Africa. The levels of pesticides measured in whole blood samples of live
      specimens were compared between nestlings from two natural breeding colonies,
      adults from a wildlife area and birds held in captivity. Statistically
      significant (P<0.05) differences between populations were detected in geometric
      means calculated for gamma-BHC (lindane), alpha(cis)-chlordane and alpha
      endosulfan. Five of the organochlorine contaminants displayed significant
      variations between concentrations detected in the clotted blood, organs and
      muscles excised from vulture carcasses. This includes residues of gamma-BHC,
      alpha-chlordane, dieldrin, beta-endosulfan and heptachlor epoxide. Values of the
      respective biocides measured in vulture samples were generally low in comparison
      to results documented for a number of avian species. Although no threat is posed
      by any of the organochloride pesticides, continual monitoring of especially
      breeding colonies is recommended. Furthermore, the suitability of African
      whitebacked vulture nestlings as basic bioindicators is highly advocated.

PMID- 11461841
TI  - Disruption of pituitary-ovarian axis by carbofuran in catfish, Heteropneustes
      fossilis (Bloch).
AB  - We investigated whether carbofuran (CF), a carbamate pesticide, at sub-lethal
      concentration had any adverse effects on reproductive function of the Indian
      catfish, Heteropneustes fossilis. 17beta-Estradiol content of serum and ovary of
      pre-spawning (P) and spawning (S) fish was reduced after sub-lethal concentration
      of carbofuran treatment (0.5-2 mg/ml, 30 days). After 30 days of CF treatment,
      the serum and ovarian vitellogenin levels of fish at the P stage were also
      reduced but remained unaltered in the S stage. The staining intensity of the
      pituitary gonadotrophs of the pre-spawning fish was significantly higher in CF
      treated fish compared to controls suggesting the inability of the pituitary
      gonadotrophs to release gonadotropin following CF treatment. CF thus acts as an
      antiestrogenic, endocrine-disrupting agent in fish, possibly targeting the
      pituitary-gonad axis.

PMID- 11461842
TI  - Metabolic costs incurred by crayfish (Procambarus acutus) in a trace element
      polluted habitat: further evidence of similar responses among diverse taxonomic
      groups.
AB  - Recent studies of several vertebrates and an invertebrate have shown elevated
      standard metabolic rate (SMR) following chronic exposure to a mixture of trace
      elements in a contaminated habitat. In this study, we examined whether another
      invertebrate, a crayfish (Procambarus acutus), also experienced elevated SMR in
      response to the same contaminants. We compared SMR of individuals inhabiting the
      contaminated site with SMR of individuals from uncontaminated reference sites. We
      also examined SMR of individuals collected from the reference areas and exposed
      in the laboratory for 50 days to sediment and food derived from the contaminated
      site. Individuals collected from the contaminated site had elevated SMR compared
      to individuals collected from the unpolluted areas (25.1 vs. 19.2 J g(-1) day(
      1)). Individuals exposed to contaminated sediment and food in the laboratory
      experienced elevations in SMR compared to controls after 27 days of exposure
      (35.2 vs. 29.4 J g(-1) day(-1)), but after 50 days of exposure, metabolic rate no
      longer differed between treatments. Growth of contaminant-exposed individuals was
      lower than growth of reference animals throughout the laboratory study. Elevated
      SMR associated with contaminant exposure may reflect energy-demanding mechanisms
      required to combat deleterious effects of contaminants. Our results support the
      prediction that increases in energy expenditure in the contaminated habitat would
      negatively influence production processes, such as growth. Results from this
      study in conjunction with observations from other species suggest that increased
      SMR is a common response among several taxa to the mixture of contaminants in the
      study site.

PMID- 11461843
TI  - Gender difference in enzymes related with alcohol consumption in hamster, an avid
      consumer of alcohol.
AB  - Syrian golden hamster (Mesocricetus auratus) is extraordinary among laboratory
      rodents in its ability to drink alcohol. After being given a free choice between
      15% ethanol and water for 5 days, both male and female hamsters derived at least
      85% of the fluid intake from the ethanol solution. Analysis of the alcohol
      metabolizing enzymes in alcohol-naive hamsters showed that the male had a higher
      activity of 57%, 58% and 34% in stomach alcohol dehydrogenase, liver cytochrome
      P450 1A2 and liver aldehyde dehydrogenase, respectively, compared with the
      female. The activity of lung angiotensin-converting enzyme, which influence fluid
      intake, was twofold higher in the male. After 4 weeks of ethanol consumption, the
      activities of the hepatic alcohol-metabolizing enzymes remained unchanged except
      cytochrome P450 2E1 which increased 42% and 88% in male and female hamsters,
      respectively. A reduction of approximately 80% in the activity of cytochrome P450
      1A2 was observed in both genders. The activities of several other cytochrome P450
      enzymes were also decreased. Although ethanol consumption did not increase plasma
      aminotransferase levels, it caused a significant increase in liver weight in
      female, but not male hamsters.

PMID- 11461844
TI  - Radiation exposure in CT: why so high?

PMID- 11461845
TI  - Radiation exposure and image quality in chest CT examinations.
AB  - OBJECTIVE: The purpose of this study was to determine how changes in radiographic
      tube current affect patient dose and image quality in unenhanced chest CT
      examinations. SUBJECTS AND METHODS: Ten sets of CT images were obtained from
      patients undergoing CT-guided chest biopsies. For each patient, six images of the
      same region were obtained at settings between 40 and 280 mAs. CT data were used
      to reconstruct tomographic sections with a field of view limited to the normal
      contralateral lung. Images were printed using lung and mediastinal image display
      settings. Image quality was determined by asking radiologists to assess the
      perceived level of mottle in CT images. Five chest radiologists ranked the
      relative image quality of six images. Patient effective doses were computed for
      chest CT examinations performed at each milliampere-second setting. Radiologists
      indicated whether any perceived improvement of image quality at the higher
      radiation exposures was worth the additional radiation dose. RESULTS: The
      differences in quality of chest CT images generated at greater than or equal to
      160 mAs were negligible. Reducing the radiographic technique factor below 160 mAs
      resulted in a perceptible reduction in image quality. Differences in CT image
      quality for radiographic techniques between 120 and 280 mAs were deemed to be
      insufficient to justify any additional patient exposure. However, the use of 40
      mAs results in an inferior image quality that would justify increased patient
      exposure. CONCLUSION: Radiographic techniques for unenhanced chest CT
      examinations can be reduced from 280 to 120 mAs without compromising image
      quality.

PMID- 11461846
TI  - Radiation exposures to patients from CT: reality, public perception, and policy.

PMID- 11461847
TI  - Radiation dose management: weighing risk versus benefit.

PMID- 11461848
TI  - Sedation and analgesia in MR imaging.

PMID- 11461849
TI  - Uterine artery embolization for the treatment of adenomyosis: clinical response
      and evaluation with MR imaging.
AB  - OBJECTIVE: This study was performed to evaluate the MR imaging appearance and
      clinical response of patients undergoing uterine artery embolization for the
      treatment of menorrhagia due to adenomyosis. MATERIALS AND METHODS: A
      retrospective review of 15 patients with adenomyosis and menorrhagia who
      underwent uterine artery embolization was performed. The diagnosis of adenomyosis
      was based on established MR imaging criteria. Clinical response was assessed at a
      minimum of 3 months after embolization. Follow-up MR imaging was performed 6
      months after embolization. RESULTS: Of the 15 patients in this study, five had
      diffuse adenomyosis without evidence of uterine fibroids, one had focal
      adenomyosis without evidence of uterine fibroids, and the remaining nine had
      adenomyosis with one or more fibroids. At follow-up, 12 (92.3%) of the 13
      patients reported significant improvement in presenting symptoms and quality of
      life. One patient continued experiencing menorrhagia, and one patient experienced
      amenorrhea during the 5 months of follow-up after embolization. MR imaging in
      nine patients, performed at a mean of 5.9 months after embolization, revealed
      significant reductions in median uterine volume (42%), median fibroid volume
      (71%), and mean-junctional-zone thickness (11 mm; 33%; p < 0.5). Six of the nine
      patients had subendometrial regions of decreased T2 signal intensity after
      embolization. CONCLUSION: Uterine artery embolization is a promising nonsurgical
      alternative for patients with menorrhagia and adenomyosis. Significant
      improvement in presenting symptoms and in quality of life is associated with
      decreases in uterine size and junctional zone thickness. Larger prospective
      studies are needed to establish the safety and efficacy of this procedure for
      patients with adenomyosis.

PMID- 11461850
TI  - Gadolinium-enhanced MR imaging in the evaluation of uterine fibroids treated with
      uterine artery embolization.
AB  - OBJECTIVE: The purpose of this study was to determine whether tumor volume
      reduction can be predicted by the infarction rate of uterine fibroids as seen on
      gadolinium-enhanced MR images obtained immediately after uterine artery
      embolization. MATERIALS AND METHODS: In our study, 36 women with symptomatic
      uterine fibroids successfully underwent uterine artery embolization. Unenhanced
      and enhanced MR imaging was performed before the procedure and repeated at 1
      week, 4 months, and 1 year after the procedure. We retrospectively reviewed
      enhanced MR images of uterine fibroids after uterine artery embolization. At 4
      months after uterine artery embolization, we compared the rate of tumor volume
      reduction in patients with completely infarcted dominant fibroids with the rate
      of tumor volume reduction in patients with partially infarcted fibroids. RESULTS:
      Enhanced MR images obtained 1 week after uterine artery embolization revealed
      that 100% infarction rates of the dominant uterine fibroids were achieved in 33
      women (92%), and 70--90% infarction rates were seen in the remaining three (8%).
      They also revealed that of a total of 204 fibroids in these patients, 100%
      infarction was achieved in 199 fibroids (98%). Enhanced MR images obtained 4
      months after uterine artery embolization showed that tumor volume reduction of
      the completely infarcted dominant fibroids (n = 23) was 60% +/- 18%, whereas that
      of the partially infarcted fibroids (n = 5) was 35% +/- 27% (p = 0.0367).
      CONCLUSION: Gadolinium-enhanced MR imaging is a useful diagnostic technique for
      uterine fibroids after uterine artery embolization because it assesses the degree
      of infarction in the embolized fibroids, which corresponds to the subsequent
      tumor volume reduction.

PMID- 11461851
TI  - Sonographically guided thrombin injection of iatrogenic femoral pseudoaneurysms:
      further experience of a single institution.
AB  - OBJECTIVE: In September 1998, we began to treat iatrogenic femoral
      pseudoaneurysms with direct thrombin injection under sonographic guidance. Our
      purpose was to determine the success and complication rate of this technique.
      SUBJECTS AND METHODS: We treated 114 consecutive patients who had iatrogenic
      femoral pseudoaneurysms using direct thrombin injection. A 22-gauge spinal needle
      was placed into the pseudoaneurysm lumen with sonographic guidance, and bovine or
      human thrombin (mean dose, 306 U; range, 50--1600 U) was injected under
      continuous color Doppler sonographic visualization. Distal pulses were monitored.
      Patient demographics, clinical variables, and pseudoaneurysm characteristics were
      collected. RESULTS: One hundred three (90%) of 114 patients had pseudoaneurysm
      thrombosis after the first procedure. Of the remaining 11 patients who required a
      second procedure 1 day later, thrombosis occurred in seven (64%) of 11. Thus, the
      overall success rate was 96% (110/114). Of the patients who required one
      injection, the mean thrombosis time was 12 sec (range, 3--90 sec). Three (3%) of
      114 patients required conscious sedation. Of the patients with successful
      thrombosis, 24-hr follow-up sonograms showed no recurrent pseudoaneurysm. Four
      patients (4%) had potential complications: a "blue toe" 15 hr after the thrombin
      injection that resolved spontaneously, a groin abscess, leg ischemia that
      resolved spontaneously after 4 hr, and crampy buttock pain that resolved
      spontaneously. CONCLUSION: For the treatment of iatrogenic femoral
      pseudoaneurysms, thrombin injection under sonographic guidance is a quick and
      effective method of therapy. Failures and complications are infrequent. At our
      institution, sonographically guided thrombin injection has replaced compression
      repair.

PMID- 11461852
TI  - A rapid low-cost uncrossed sheath method for clearing thrombosed hemodialysis
      grafts.

PMID- 11461853
TI  - Deep venous thrombosis: spectrum of findings and pitfalls in interpretation on CT
      venography.

PMID- 11461855
TI  - Relationship between duration of pain and secondary signs of obstruction of the
      urinary tract on unenhanced helical CT.
AB  - OBJECTIVE: The objective of this study was to investigate the relationship
      between duration of flank pain and the frequency of secondary signs of ureteral
      obstruction on unenhanced helical CT. SUBJECTS AND METHODS: The duration of flank
      pain was prospectively determined in 227 consecutive patients diagnosed with
      acute ureterolithiasis on unenhanced helical CT. These CT studies were evaluated
      for the presence or absence of perinephric stranding, ureteral dilatation,
      perinephric fluid, collecting system dilatation, periureteral stranding, and
      nephromegaly. The frequency of each sign was determined as a function of the
      duration of pain. RESULTS: The frequency of moderate or severe perinephric
      stranding increased from 5% at 1--2 hr to 51% at 7--8 hr (p < 0.001); ureteral
      dilatation increased from 84% at 1--2 hr to 97% at more than 8 hr (p < 0.03);
      moderate or severe perinephric fluid increased from 0% at 1--2 hr to 22% at 3--4
      hr (p < 0.03); collecting system dilatation increased from 68% at 1--2 hr to 89%
      at 7-8 hr (p < 0.03); periureteral stranding increased from 35% at 1--2 hr to 76%
      at 7--8 hr (p < 0.004); and nephromegaly increased from 40% at 1--2 hr to 54% at
      7--8 hr (p < 0.36). CONCLUSION: All CT secondary signs of ureteral obstruction
      except nephromegaly showed a significant increase in frequency as duration of
      flank pain increased. This observation may explain why the CT studies of some
      patients with acute ureterolithiasis show negative findings for some or all CT
      secondary signs of obstruction. Therefore, knowledge of the duration of pain is
      important when interpreting unenhanced CT studies in patients with acute
      ureterolithiasis.

PMID- 11461856
TI  - Urinary calculi on computed radiography: comparison of observer performance with
      hard-copy versus soft-copy images on different viewer systems.
AB  - OBJECTIVE: The purpose of this study was to compare observer performance for
      detecting urinary calculi using abdominal computed radiography with hard-copy
      versus soft-copy images and with a high-resolution video monitor versus a liquid
      crystal-display (LCD) monitor. MATERIALS AND METHODS: We compared observer
      performance for detecting urinary calculi using three sets of radiographs-hard
      copy images, soft-copy images displayed on a LCD monitor (1280 x 1024 bits), and
      soft-copy images displayed on a high-resolution video monitor using receiver
      operating characteristic curve analysis with a continuous rating scale. Computed
      radiography was archived with a 2140 x 1760 pixel resolution and a 10-bit depth.
      The selected data set included 62 images: 27 images showing proven urinary
      calculi smaller than 6 mm and three in number, and 35 images containing no proven
      abnormalities. Eleven radiologists (three genitourinary radiologists and eight
      general radiologists) participated in the study. Interpretations of three sets of
      randomly distributed radiographs were performed individually in three separate
      sessions at 1-week intervals. RESULTS: No statistically significant differences
      were found in the area under the receiver operating characteristic curve for
      detecting urinary calculi or in the interpreting times between soft-copy and hard
      copy images; the mean areas under the receiver operating characteristic curve of
      hard-copy images, soft-copy images displayed on an LCD monitor, and soft-copy
      images displayed on a high-resolution video monitor were 0.579, 0.610, and 0.732,
      respectively. However, soft-copy images showed relatively improved diagnostic
      accuracy among less experienced radiologists (p < 0.05). CONCLUSION: For
      detecting urinary calculi, soft-copy images offered a diagnostic accuracy similar
      to or slightly more accurate than that of hard-copy images obtained in a laser
      printed film-based environment. The diagnostic performance with soft-copy images
      viewed on an LCD monitor was comparable to that of soft-copy images viewed on a
      high-resolution video monitor.

PMID- 11461857
TI  - Radio-pathologic conferences of the Massachusetts General Hospital.
      Posttransplantation non-Hodgkin's lymphoma of the adrenal gland.

PMID- 11461858
TI  - Sonohysterography for evaluation of the endometrium in women treated with
      tamoxifen.
AB  - OBJECTIVE: This study was performed to evaluate sonohysterography for the
      diagnosis of endometrial abnormalities in women treated with tamoxifen. MATERIALS
      AND METHODS: Fifty sonohysterograms were obtained in 48 consecutive tamoxifen
      treated women. All women were postmenopausal and had been undergoing tamoxifen
      therapy for a mean of 2.6 years. Forty-six sonohysterograms (92%) were completed
      and four were unsuccessful. Sonohysterogram findings were correlated with prior
      endometrial biopsy results for 23 sonohysterograms (46%) that were preceded by
      endometrial biopsy. Sonohysterogram findings were also compared with
      histopathology results, available for 38 sonohysterograms (76%) that were
      followed by hysteroscopy with dilatation and curettage. RESULTS:
      Sonohysterography revealed 31 endometrial polyps (62%), six thickened endometria
      (12%), five normal endometria (10%), and four subendometrial cysts (8%). Surgery
      was avoided when seven sonohysterograms (14%) revealed normal endometria or
      subendometrial cysts. In the group with histopathologic correlation, 23 of 28
      polyps were confirmed and two of five thickened endometria were shown to
      represent endometrial hyperplasia. Twelve (63%) of 19 sonohysterograms with prior
      normal endometrial biopsy findings had abnormalities on sonohysterography,
      including 10 polyps and two thickened endometria. CONCLUSION: Sonohysterography
      aids the diagnosis of endometrial abnormalities in tamoxifen-treated women even
      if prior endometrial biopsies have negative findings. In 14% of cases,
      visualization of a normal endometrium on sonohysterography obviated surgery.

PMID- 11461859
TI  - Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison
      of CT, MR imaging, and positron emission tomography.
AB  - OBJECTIVE: Accurate assessment of lymph node status before treatment is critical
      in the treatment of gynecologic cancers because the 5-year survival and treatment
      of women is influenced by lymph node involvement. The aims of this study were to
      investigate the ability of X-ray CT, MR imaging, and (18)F-FDG positron emission
      tomography (PET) to detect pelvic lymph node metastases by comparing imaging with
      histopathologic findings after lymph node dissection. MATERIALS AND METHODS:
      Eighteen patients with gynecologic cancers were studied by all three imaging
      methods before surgery. The images were initially reviewed with routine
      diagnostic conditions and then, subsequently, by two observers who were unaware
      of the clinical and histopathologic findings of the patients. The nodal sites
      were split into upper (aortic to common iliac bifurcations) and lower (common
      iliac bifurcations to inguinal ligament) iliac chains. All observers' results
      were statistically analyzed with specificity, sensitivity, positive and negative
      predictive values, Fisher's exact test (individual observers) or chi-square test
      (combined observers), and Cohen's kappa test. RESULTS: Eight of 18 patients had
      lymph node metastases at histology. Findings of all three modalities agreed in
      full in only one patient. CT correctly revealed 10 node-negative patients,
      whereas MR imaging was correct in eight of these patients. (18)F-FDG PET
      correctly depicted one patient with lymph nodes negative for tumor. CT was the
      most specific imaging modality (97.0%), with MR imaging and PET rendering values
      of 90.7% and 77.3%, respectively, but sensitivity of all modalities was low (CT,
      48.1%; MR imaging, 53.7%; PET, 24.5%). Observer agreement for each modality was
      good; kappa values among all observers were 0.88 for CT, 0.85 for MR imaging, and
      0.72 for PET. CONCLUSION: CT is the most specific modality for detecting lymph
      nodes positive for tumor in gynecologic cancers, whereas MR imaging is the most
      sensitive. The poor results of PET in the pelvis are attributed to urinary (18)F
      FDG in the ureters or bladder, which may mask or imitate lymph node metastases.

PMID- 11461860
TI  - Noninvasive imaging of living related kidney donors: evaluation with CT
      angiography and gadolinium-enhanced MR angiography.
AB  - OBJECTIVE: This study was performed to determine whether noninvasive imaging with
      CT angiography and MR angiography in the preoperative investigation of living,
      related kidney donors provides sufficient information for the surgeon. MATERIALS
      AND METHODS: Eighty consecutive potential living kidney donors were investigated.
      Fifty patients underwent CT angiography and 30 underwent MR angiography before
      donor nephrectomy. CT was performed using 3-mm collimation with a pitch of 1.6
      after the injection of 150 mL of nonionic contrast medium. The axial data,
      multiplanar reconstructions, and maximum intensity projections were reviewed. MR
      angiography was performed on a 1-T magnet using a contrast-enhanced three
      dimensional gradient echo technique. Maximum intensity projections and axial
      reformations were reviewed. Imaging findings were compared with the surgical
      results in 54 patients. RESULTS: CT angiography and MR angiography were 100%
      sensitive in identifying the main renal arteries and renal veins. CT angiography
      visualized 37 of the 40 arteries identified at surgery, for a detection rate of
      93%. MR angiography visualized 18 of the 20 arteries identified at surgery, a
      detection rate of 90%. CONCLUSION: CT angiography and MR angiography are suitable
      for the noninvasive investigation of living kidney donors and provide all the
      information required by the surgeon. Both methods may miss small accessory renal
      arteries. MR angiography does not use potentially toxic contrast material or
      radiation and is the preferred investigation, with CT angiography reserved for
      patients unable to tolerate MR imaging.

PMID- 11461861
TI  - Inferior vena cava thrombosis: a mechanism of posttraumatic adrenal hemorrhage.

PMID- 11461862
TI  - Comparison of balloon- and mushroom-retained large-bore gastrostomy catheters.
AB  - OBJECTIVE: We conducted a retrospective study to evaluate two different types of
      percutaneous fluoroscopic gastrostomy procedures and catheters. MATERIALS AND
      METHODS: Between July 8, 1999, and August 4, 2000, 80 percutaneous gastrostomy
      catheters were placed in 80 patients in 80 attempts. Twenty-five 16-, 18-, or 20
      French balloon-retained catheters and 55 20-French mushroom-retained catheters
      were inserted. Typically, the type of catheters placed was based on operator
      preference. However, balloon-retained tubes were preferred for use in patients
      with obstructive head and neck or esophageal malignancies, and mushroom-retained
      catheters were preferred for use in demented or combative patients. Follow-up was
      conducted through chart reviews and telephone interviews. The technical success,
      procedural complications, and catheter complications were recorded. Chi-square
      statistical analysis was performed. RESULTS: Technical success was 100% (80/80
      patients), and no procedural complications occurred. In patients who received
      balloon-retained catheters, the major complication rate was 0%, the minor
      complication rate was 8% (2/25 patients), and the tube complication rate was 68%
      (17/25 patients). The following complications occurred: catheter dislodgment (n =
      17), superficial cellulitis (n = 1), and bleeding gastric ulcer (n = 1). In
      patients who received mushroom-retained catheters, the major complication rate
      was 0%, the minor complication rate was 3.6% (2/55 patients), and the tube
      complication rate was 3.6% (2/55 patients). The following complications occurred:
      superficial cellulitis (n = 2), tube occlusion (n = 1), and peristomal tube
      leakage (n = 1). No significant differences in major or minor complications were
      found between the gastrostomy procedures. Balloon-retained catheters had a
      significantly higher rate of tube complications (p < 0.001). CONCLUSION: Compared
      with balloon-retained catheters, mushroom-retained gastrostomy catheters are
      significantly more durable, more secure, and less prone to tube dysfunction.
      Mushroom-retained catheters should be the preferred type of gastrostomy catheter
      to place in patients whenever possible.

PMID- 11461863
TI  - Prevalence of incidental Bochdalek's hernia in a large adult population.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence and
      characteristics of adult Bochdalek's hernia in a large patient population.
      MATERIALS AND METHODS: We retrospectively reviewed all abdominal CT scans
      obtained at our hospital in 1998. Patients in our study were identified through a
      keyword search of our database for "Bochdalek," "hernia," and "diaphragm." The
      individual patient studies identified were reviewed in a soft-copy format. We
      noted the location and side of the body on which the diaphragmatic hernia arose
      and the contents of the sac. We also performed a chart review for each patient
      included in the study, noting the patient's sex, age, and symptoms. RESULTS:
      Incidental Bochdalek's hernia was diagnosed in 22 patients (17 women, five men),
      which represents an incidence of 0.17% based on 13,138 abdominal CT reports we
      reviewed. The mean age of the patients was 66.6 years. None of the patients were
      symptomatic. Sixty-eight percent of the hernias were on the right side of the
      body, 18% were on the left side, and 14% were bilateral. Seventy-three percent
      contained only fat or omentum, whereas 27% had solid or enteric organ involvement
      including the spleen, small intestine, or large intestine. CONCLUSION:
      Bochdalek's hernia is not rare, and the incidence of Bochdalek's hernias that
      contain enteric tract is higher than previously reported. This incidence likely
      represents a conservative estimate because some Bochdalek's hernias may have been
      overlooked or unreported.

PMID- 11461864
TI  - Pancreatic mass due to chronic pancreatitis: correlation of CT and MR imaging
      features with pathologic findings.
AB  - OBJECTIVE: The purpose of this study was to identify helical CT and MR imaging
      features of pancreatic masses (focal enlargement) due to chronic pancreatitis and
      their correlation with pathologic findings. CONCLUSION: When histologic fibrosis
      is uniformly present through the pancreas in patients with chronic pancreatitis,
      there is no demarcation of masses due to chronic pancreatitis. When there is a
      greater degree of histologic fibrosis in the masslike part of the pancreas, the
      mass is often demarcated from the remaining pancreas, and the enhancement pattern
      on two-phase helical CT and dynamic gadolinium-enhanced MR imaging mimics that of
      pancreatic adenocarcinoma.

PMID- 11461866
TI  - Hiatal hernia with pancreatic volvulus: a rare cause of acute pancreatitis.

PMID- 11461867
TI  - Hepatocellular carcinoma treated with radiofrequency ablation: comparison of
      pulse inversion contrast-enhanced harmonic sonography, contrast-enhanced power
      Doppler sonography, and helical CT.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of contrast
      enhanced pulse inversion harmonic imaging with contrast-enhanced power Doppler
      sonography and helical CT to determine incomplete local treatment after
      radiofrequency ablation in patients with hepatocellular carcinoma. MATERIALS AND
      METHODS: Thirty-five consecutive patients (24 men and 11 women; mean age, 64
      years) with 43 hepatocellular carcinomas (3.6 +/- 1.1 cm) were treated using
      internally cooled radiofrequency ablation therapy. Therapeutic response was
      evaluated at 4 months with dual-phase contrast-enhanced helical CT, conventional
      power Doppler Sonography, and pulse inversion harmonic imaging using a
      sonographic contrast agent (SH-508). CT and sonographic studies were reviewed
      separately in random order by four radiologists at different consensus
      conferences. Sensitivity and specificity of the sonographic methods were
      determined using CT as a gold standard and results were compared using the
      McNemar test. RESULTS: CT examinations identified residual tumor in 12 lesions
      (27.9%). Although conventional contrast-enhanced power Doppler sonography
      identified residual viable tumor foci in four incompletely treated lesions
      (9.3%), contrast-enhanced pulse inversion harmonic imaging identified residual
      tumoral enhancement in 10 lesions (23.3%). Thus, the sensitivity of pulse
      inversion harmonic imaging (83.3%) was significantly greater (p < 0.05) for
      detecting residual nonablated tumor compared with conventional contrast-enhanced
      power Doppler sonography. CONCLUSION: Our study suggests that contrast-enhanced
      pulse inversion harmonic imaging may enable the detection of residual nonablated
      tumor in more cases than contrast-enhanced power Doppler sonography and may
      ultimately prove to be a useful adjunct for percutaneous ablation therapies.
      Nevertheless, contrast-enhanced axial imaging (CT or MR imaging) is currently the
      most sensitive test for managing thermal ablation for patients with
      hepatocellular carcinoma.

PMID- 11461868
TI  - Tumor recurrence after radiofrequency thermal ablation of hepatic tumors:
      spectrum of findings on dual-phase contrast-enhanced CT.
AB  - OBJECTIVE: We conducted this study to determine the spectrum of CT findings of
      tumor recurrence after radiofrequency ablation of primary and secondary malignant
      hepatic tumors. MATERIALS AND METHODS: Twenty-five patients, 10 with
      hepatocellular carcinoma (HCC) and 15 patients with metastases who developed
      tumor recurrence after radiofrequency ablation of hepatic neoplasms, formed the
      study population. Three observers reviewed the CT scans of these patients and
      evaluated the location (local intrahepatic, remote intrahepatic, or extrahepatic)
      of all recurrent lesions and the morphology and enhancement characteristics of
      local intrahepatic recurrences. RESULTS: Local intrahepatic recurrences were seen
      in nine patients (90%) and 11 patients (73%); remote intrahepatic recurrences, in
      five patients (50%) and seven patients (45%); and extrahepatic recurrences, in
      zero and six patients (40%) with recurrent HCC and recurrent metastases,
      respectively. Of the 12 nodules of local intrahepatic recurrences in HCC and the
      24 in metastases, the patterns of local intrahepatic recurrences were of nodular,
      halo, and gross enlargement types in eight (67%) and nine (38%), four (33%) and
      six (38%), and zero and nine (37%) nodules in HCC and hepatic metastases,
      respectively. The number of local intrahepatic recurrent lesions enhancing in the
      arterial phase was significantly greater in HCC. CONCLUSION: Tumor recurrences
      occurred at intra- and extrahepatic sites after radiofrequency ablation of
      hepatic neoplasms. The local intrahepatic recurrences appeared in three patterns:
      nodular, halo, or gross enlargement. The sites of recurrence and the morphologic
      patterns of local intrahepatic tumor recurrence differed between primary and
      secondary hepatic neoplasms.

PMID- 11461869
TI  - Anatomic variants of the biliary tree: MR cholangiographic findings and clinical
      applications.

PMID- 11461870
TI  - Intraoperative sonography of the biliary system.

PMID- 11461871
TI  - Sonographically guided directional vacuum-assisted breast biopsy using a handheld
      device.
AB  - OBJECTIVE: The goal of this study was to show that one can safely remove all
      sonographic evidence of masses in the breast less than or equal to 1.5 cm in
      greatest dimension using the 11-gauge handheld Mammotome, thereby reducing the
      possibility of a false-negative diagnosis and other shortcomings of the automated
      core biopsy device. SUBJECTS AND METHODS: Over a 12-week period (May 3--July 31,
      2000), 124 sonographically guided breast biopsies were performed in 113 patients,
      using a new handheld directional vacuum-assisted biopsy device. All lesions that
      were less than or equal to 1.5 cm were biopsied using a handheld Mammotome; an
      attempt was made to continue the biopsy until no sonographic evidence of the
      lesion remained. RESULTS: Of these 124 lesions, 14 had infiltrating ductal
      carcinomas, four had infiltrating ductal carcinomas with associated ductal
      carcinoma in situ, one had infiltrating lobular carcinoma, one had ductal
      carcinoma in situ, three had atypical ductal hyperplasias, one had atypical
      lobular hyperplasia, and one had phyllodes tumor. Only one infiltrating ductal
      carcinoma was entirely removed histologically at Mammotome biopsy. There were no
      underestimates of disease. No cases of epithelial displacement were observed in
      any of the surgical excisions of malignancies. The remaining 99 lesions were
      benign. CONCLUSION: The handheld Mammotome diminishes the shortcomings of the
      automated core biopsy device. It reduces the possibility of false-negatives and
      underestimation of disease. It eliminates the need for multiple insertions and
      reduces the likelihood of epithelial displacement. As a result, we now use this
      device for all sonographically guided biopsies of breast masses smaller than 1.5
      cm and recommend that others consider it for such use.

PMID- 11461872
TI  - MR imaging of meniscal cysts: incidence, location, and clinical significance.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of medial
      versus lateral meniscal cysts as seen on MR imaging. MATERIALS AND METHODS: A
      total of 2572 knee MR imaging reports were retrospectively reviewed for the
      presence of meniscal tears and cysts. Two musculoskeletal radiologists reviewed
      all images with reported cysts. The type and location of meniscal tear and the
      presence and location of meniscal cysts were recorded. RESULTS: A total of 1402
      meniscal tears were reported in 2572 MR examinations (922 [66%] of 1402 in the
      medial compartment; 480 [34%] of 1402 in the lateral compartment). Meniscal cysts
      were present in 109 (4%) of 2572 knees. Of the 109 cysts, 72 (66%) were in the
      medial compartment, and 37 (34%) were in the lateral compartment. Meniscal cysts
      were found in association with 72 (7.8%) of the 922 medial meniscal tears and 37
      (7.7%) of the 480 lateral meniscal tears. Meniscal cysts showed direct contact
      with an adjacent meniscal tear in 107 (98%) of 109 cases, with the tear showing a
      horizontal component in 96 (90%) of 107 cases. CONCLUSION: Meniscal cysts occur
      almost twice as often in the medial compartment as in the lateral compartment.
      Medial and lateral tears occur with the same frequency. These findings, when
      viewed in the context of the historical literature on meniscal cysts, suggest
      that MR imaging detects a greater number of medial meniscal cysts than physical
      examination or arthroscopy, and that MR imaging can have an important impact on
      surgical treatment of patients.

PMID- 11461873
TI  - Examination of postoperative peripheral nerve lesions with high-resolution
      sonography.
AB  - OBJECTIVE: Peripheral nerve lesions after surgery are common and are related
      either to direct compromise of the nerve by the surgical procedure (iatrogenic
      lesions) or to postoperative events such as scar formation. Despite a high
      sensitivity, electrodiagnosis may not reveal the exact location and cause of a
      nerve lesion. We hypothesized that high-resolution sonography could be helpful in
      diagnosing postoperative peripheral nerve lesions by direct visualization of the
      nerve and surrounding tissues. SUBJECTS AND METHODS: Eighteen patients with
      postoperative peripheral nerve lesions that were confirmed with clinical
      examination and electrodiagnosis were examined on sonography. Eight patients had
      lesions caused by direct nerve surgery, and 10 patients had undergone a previous
      orthopedic operation or open biopsy. Sonographic diagnoses were correlated with
      neurologic examinations and surgical findings. RESULTS: Reliable visualization of
      injured nerves on sonography was feasible in all patients. Axonal swelling of a
      nerve was diagnosed in three patients, direct compromise of a nerve by
      surrounding scar tissue or surgical implants was diagnosed in 10 patients, a
      neuroma was diagnosed in three, and insufficient surgical repair, in two.
      Sonographic findings were confirmed during surgery in all except one patient.
      CONCLUSION: In contrast to electrophysiologic tests, high-resolution sonography
      can show the exact location, extent, and type of a postoperative peripheral nerve
      lesion and the concurrent disease of surrounding tissues. Because the latter can
      often be the causative agent for the development of a lesion or the lack of
      improvement with conservative treatment, sonography yields important information
      that may not be obtained with other diagnostic modalities.

PMID- 11461874
TI  - MR imaging of bone marrow in glycogen storage disease type IB in children and
      young adults.
AB  - OBJECTIVE: Patients with glycogen storage disease type IB have neutropenia and
      neutrophil dysfunction that predispose them to frequent infections, for which
      they are given granulocyte colony--stimulating factor. Because neutropenia is a
      consequence of defects in myeloid maturation, the bone marrow aspirations show
      hypercellularity due to myeloid hyperplasia. This study evaluated MR imaging of
      bone marrow in glycogen storage disease type IB with and without granulocyte
      colony-stimulating factor. CONCLUSION: As confirmed by the histologic results in
      bone marrow aspirations, abnormal findings on MR images of bone marrow in
      patients with glycogen storage disease type IB indicate an increased myelopoietic
      activity, which is augmented by treatment with granulocyte colony-stimulating
      factor.

PMID- 11461876
TI  - Sedatives used in pediatric imaging: comparison of IV pentobarbital with IV
      pentobarbital with midazolam added.
AB  - OBJECTIVE: This study was designed to evaluate safety, efficacy, and success of
      adding IV midazolam to an established IV pentobarbital protocol for pediatric
      sedation for radiologic imaging. Outcomes included sedation and discharge times
      as well as adverse events SUBJECTS AND METHODS: This prospective study compared
      two different sedation protocols developed by the radiology sedation committee
      and approved by the hospital sedation committee at our institution. Patients in
      the pentobarbital group received IV pentobarbital alone, and patients in the
      pentobarbital--midazolam group received a combination of IV pentobarbital and
      midazolam. A total of 1070 infants and children were enrolled, and sedation data
      were entered into a computer database and reviewed at bimonthly radiology
      sedation committee meetings for safety, efficacy, efficiency, failed sedations,
      and adverse outcomes. RESULTS: Mean age distribution, sex, American Society of
      Anesthesiologists physical status classification, fasting status, weight, and
      types of examinations were similarly distributed between the two study groups.
      Analysis of variance indicated longer times were required to sedate and to
      discharge patients who had received pentobarbital--midazolam (p < 0.001 for both
      times), even after adjusting for differences in the patients' ages and weights.
      The pentobarbital--midazolam group required more time to be successfully sedated
      and more time to discharge from the recovery room. The rates of adverse events
      and failed sedations were similar for both groups. CONCLUSION: Midazolam does not
      have a beneficial effect on pentobarbital sedation and has no effect on the rate
      of adverse events. The prolonged time needed both to sedate and to discharge
      (timed from the initial dose of sedation) pediatric patients who have received
      midazolam should discourage physicians from combining it with pentobarbital for
      pediatric sedation.

PMID- 11461877
TI  - CT of small-bowel obstruction in children: sensitivity and specificity.
AB  - OBJECTIVE.:The aim of this study was to determine the sensitivity, specificity,
      and accuracy of CT in the diagnosis of small-bowel obstruction in children.
      MATERIALS AND METHODS: The CT scans of 30 children with surgically proven small
      bowel obstruction, 22 children with ileus, and 29 children who served as controls
      were retrospectively reviewed by two of four interpreters who were unaware of the
      children's final diagnoses. Causes of obstruction in the patients included 19
      adhesions, six cases of volvulus, five intussusceptions, four strictures, and two
      cases each of internal hernia and abscess. Eight obstructions had multiple
      causes. The CT scans were evaluated for the presence of small-bowel obstruction
      using a scale with five degrees of confidence. In cases of discrepancy of more
      than one level of certainty, a third interpreter was consulted. Criteria for
      small-bowel obstruction included a discrepancy in caliber between the proximal
      dilated and the more distal small bowels or generalized small-bowel dilatation
      (>2.5 cm) in the presence of a collapsed colon. An interpreter's rating that an
      obstruction was either present or probable was considered a positive finding; a
      rating indicating that the interpreter was not sure whether an obstruction was
      present or believed that an obstruction was not probable or saw normal anatomic
      structures was considered a negative finding for small-bowel obstruction. The
      cause and level of obstruction also were recorded. RESULTS: There were 26 true
      positive (87%) and four false-negative (13%) interpretations for small-bowel
      obstruction. Among the interpretations of scans of patients with ileus, 68% were
      true-negative and 32% were false-positive interpretations for small-bowel
      obstruction. Among the control group, there were no false-positive readings.
      Sensitivity of CT was 87%, specificity was 86%, and accuracy was 86%. In the
      scans of children 2 years and younger, CT had a sensitivity of 100% and
      specificity of 0%. Of the patients with surgically confirmed levels of
      obstruction, the correct level of obstruction was described by both interpreters
      in 12 (86%) of 14 scans. The causes of obstruction were correctly identified in
      14 (47%) of 30 scans. CONCLUSION: CT is both sensitive and specific for use in
      diagnosing small-bowel obstruction in children, especially in children older than
      2 years.

PMID- 11461878
TI  - Using edge enhancement to identify subtle findings on soft-copy neonatal chest
      radiographs.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether edge enhancement
      could improve the visibility of subtle findings on soft copies of neonatal chest
      radiographs. MATERIALS AND METHODS: Two radiologists reviewed 82 soft-copy
      neonatal chest radiographs before and after the application of edge enhancement
      on our picture archiving and communication system (PACS). The visibility of a
      pneumothorax (n = 22), central venous catheter (n = 32), umbilical arterial
      catheter (n = 36), endotracheal tube (n = 40), and normal anatomic structures
      (the minor fissure, anterior segmental bronchus of the right upper lobe, and
      aortic arch, n = 57) was evaluated. Six of 22 soft-copy images depicting a
      pneumothorax were excluded from the evaluation of image quality either because of
      the large size of the pneumothorax itself (n = 7) or because of the lack of
      confirmatory evidence that would have been provided by an additional lateral
      decubitus (n = 6) or cross-table lateral radiograph (n = 3). Image quality was
      evaluated by visual grading analysis. RESULTS: The visibility of a pneumothorax
      (p < 0.01), vascular catheters (p < 0.001), the minor fissure (p < 0.001), and
      the anterior segmental bronchus of the right upper lobe (p < 0.001) improved
      significantly after applying edge enhancement to soft copies of neonatal chest
      radiographs, whereas the visibility of the aortic arch did not improve.
      Evaluations of the improvements in the visibility of the endotracheal tube were
      inconsistent. CONCLUSION: Application of edge enhancement to soft copies of
      neonatal chest radiographs helps radiologists to identify small pneumothoraces,
      vascular catheters, and delicate normal structures, thereby improving the
      detection of subtle chest findings in the neonatal intensive care unit.

PMID- 11461879
TI  - Use of three-dimensional reconstructed helical CT images in recognition and
      communication of chest wall anomalies in children.

PMID- 11461880
TI  - Intraarterial subclavian artery thrombolysis in a neonate.

PMID- 11461881
TI  - Evaluating pediatric brain tumor cellularity with diffusion-tensor imaging.
AB  - OBJECTIVE: MR imaging of central nervous system (CNS) malignancies falls short of
      a definitive evaluation. Tissue diagnosis remains the gold standard. Diffusion
      tensor MR imaging measures the apparent diffusion coefficient and diffusion
      anisotropy of water in tissue. The purpose of this study was to test the
      hypothesis that the apparent diffusion coefficient may improve the MR imaging
      evaluation of newly diagnosed CNS neoplasms. We examined the relationship between
      the apparent diffusion coefficient, anisotropy, and tumor cellularity in 12
      pediatric patients. MATERIALS AND METHODS: On the basis of histopathologic
      evaluation, tumors in this case series were segregated into three types: low
      grade gliomas, embryonal tumors, and nonembryonal high-grade tumors. Mean
      apparent diffusion coefficient and anisotropy values obtained from the solid
      components of each tumor were compared with cellularity, total cellular area, and
      total nuclear area derived from biopsy material. RESULTS: The apparent diffusion
      coefficient ratio (tumor to normal brain) correlated well with tumor
      classification (p = 0.001). Anisotropy was decreased similarly in all tumor
      classifications. The absolute apparent diffusion coefficient correlated well with
      cellularity (p = 0.014) and total nuclear area (p = 0.005) per high-power field.
      The correlation between apparent diffusion coefficient and total cellular area
      per high-power field was not statistically significant. CONCLUSION: The apparent
      diffusion coefficient may be predictive of tumor classification and may be a
      useful tool in characterizing tumor cellularity and total nuclear area. These
      parameters are not available in standard MR imaging. Therefore, diffusion-tensor
      imaging may enhance the diagnostic process in pediatric CNS malignancies.

PMID- 11461882
TI  - Reliability of normal findings on MR imaging for excluding the diagnosis of
      vasculitis of the central nervous system.
AB  - OBJECTIVE: We attempt to determine whether angiography is indicated in patients
      with suspected central nervous system (CNS) vasculitis who present with negative
      findings on MR imaging studies. CONCLUSION: MR imaging findings may be negative
      in the setting of CNS vasculitis confirmed on angiography, indicating that
      advanced imaging techniques tailored to detect infarction (i.e., fluid-attenuated
      inversion recovery, diffusion-weighted, and perfusion imaging) may be necessary
      to enhance the sensitivity of an MR study and that despite the high sensitivity
      of MR imaging for CNS vasculitis, angiography may still be required to render an
      accurate diagnosis.

PMID- 11461883
TI  - Arachnoiditis ossificans: MR imaging features in five patients.
AB  - OBJECTIVE: The purpose of this article is to illustrate the appearance of
      arachnoiditis ossificans on MR imaging and discuss the implications this
      diagnosis has on treatment. CONCLUSION: In patients with arachnoiditis
      ossificans, the MR imaging findings are of linear or masslike intrathecal
      lesions, which generally have some hyperintensity on T1- weighted sequences and
      are hyper- or hypointense on T2-weighted images, in the setting of arachnoiditis.

PMID- 11461884
TI  - CT-guided labyrinthectomy: efficacious minimally invasive therapy for intractable
      episodic vertigo.

PMID- 11461886
TI  - Question and answer. Sonographic follow-up of patients with gallbladder polyps.

PMID- 11461887
TI  - Different MR angiography techniques provide different results in assessing
      extracranial carotid artery disease.

PMID- 11461888
TI  - Language of the radiology report.

PMID- 11461890
TI  - Abnormal lateral meniscal fascicles.

PMID- 11461889
TI  - CT of primary cystic pancreatic neoplasms: nihilism may be unwarranted.

PMID- 11461891
TI  - Defending the "missed" radiographic diagnosis.

PMID- 11461892
TI  - Signing a colleague's radiology report.

PMID- 11461893
TI  - "Doc, I don't wanna know!": patient-requested noninformed consent.

PMID- 11461894
TI  - CT and MR imaging of intravertebral vacuum resulting from a malignancy.

PMID- 11461895
TI  - Metastasis of thyroid cancer to the heart.

PMID- 11461896
TI  - Perirectal sinus tracks and fistulas caused by hidradenitis suppurativa.

PMID- 11461897
TI  - Aortoenteric fistula on (99m)Tc erythrocyte scintigraphy.

PMID- 11461898
TI  - N-glycosylation and residues Asn805 and Asn890 are involved in the functional
      properties of type VI adenylyl cyclase.
AB  - In this study, we demonstrate that type VI adenylyl cyclase (ACVI) is
      glycosylated in vivo. Treating HEK293 cells expressing ACVI with tunicamycin to
      block the addition of N-linked oligosaccharide or removing the N-linked
      oligosaccharide by in vitro peptidyl-N-glycosidase F digestion reduced the
      molecular mass of ACVI. Furthermore, tunicamycin treatment suppressed the
      forskolin-stimulated activity of ACVI. Mutation of either one or both potential N
      glycosylation sites (Asn(805) and Asn(890), located on extracellular loops 5 and
      6, respectively) also reduced the molecular mass of ACVI. Therefore, ACVI was
      glycosylated at both Asn(805) and Asn(890). Confocal analysis indicated that
      glycosylation was not required for the delivery of ACVI to the cell surface.
      Although no significant alterations in K(m) values for ATP or sensitivity to
      divalent cations were detected, the glycosylation-deficient ACVI mutant
      N805Q/N890Q-ACVI exhibited much lower forskolin-, Mn(2+)-, and Mg(2+)-stimulated
      cyclase activities than did wild-type ACVI. By contrast, the Galpha(s)-stimulated
      cyclase activities of wild-type ACVI and N805Q/N890Q-ACVI were indistinguishable.
      Furthermore, compared with wild-type ACVI, N805Q/N890Q-ACVI was less sensitive to
      inhibition mediated by dopamine D2 receptors or by protein kinase C.
      Collectively, glycosylation of ACVI not only affected its catalytic activity in
      an activator-dependent manner, but also altered its ability to be regulated by a
      Galpha(i) protein-coupled receptor or by protein kinase C.

PMID- 11461899
TI  - Isolation of a novel gene from Schizosaccharomyces pombe: stm1+ encoding a seven
      transmembrane loop protein that may couple with the heterotrimeric Galpha 2
      protein, Gpa2.
AB  - A putative seven transmembrane protein gene, stm1(+), which is required for
      proper recognition of nitrogen starvation signals, was isolated as a multicopy
      suppressor of a ras1 synthetic lethal mutant in Schizosaccharomyces pombe. Under
      nitrogen-deficient conditions, transcription of the stm1 gene was induced;
      deletion of stm1 was associated with early entry into G(1) arrest. Under
      nutritionally sufficient conditions, overexpression of Stm1 inhibited vegetative
      cell growth, resulted in decreased intracellular cAMP levels, increased the
      expression of the meiosis-specific genes ste11, mei2, and mam2, and facilitated
      sexual development in homothallic cells. However inhibition of vegetative cell
      growth and reduction of cAMP levels were not observed in a deletion mutant of the
      heterotrimeric G protein Galpha2 gene, gpa2, that is responsible for regulating
      intracellular cAMP levels, a key factor in determining the sexual development in
      S. pombe. Stm1 protein was shown to interact with Gpa2 through its C-terminal
      transmembrane domains 5-7. Mutation at Lys(199) in the C-terminal domain
      (stm1(K199A)) abolished the Stm1 overexpression effect on lowering cAMP levels.
      Induction of ste11, a meiosis-specific gene transcription factor, by Stm1
      overexpression was enhanced in gpa2-deleted cells but was absent in a deletion
      mutant of sty1, a key protein kinase that links mitotic control with
      environmental signals and induces stress-responsive genes. Moreover, deletion of
      both stm1 and ras1 caused delayed entry into G(1) arrest in S. pombe when the
      cells were grown in a nitrogen-deficient medium. Thus we consider that the stm1
      gene can function through Gpa2-dependent and/or -independent pathways and may
      play a role in providing the prerequisite state for entering the pheromone
      dependent differentiation cycle in which heterotrimeric Galpha1 protein, Gpa1,
      and Ras1 play major roles. Stm1 could function as a sentinel molecule sensing the
      nutritional state of the cells, stopping the proliferative cell cycle, and
      preparing the cell to enter meiosis under nutritionally deficient conditions.

PMID- 11461900
TI  - Roles of DNA fragmentation factor and poly(ADP-ribose) polymerase in an
      amplification phase of tumor necrosis factor-induced apoptosis.
AB  - During apoptosis, endonucleases cleave DNA into 50-300-kb fragments and
      subsequently into internucleosomal fragments. DNA fragmentation factor (DFF) is
      implicated in apoptotic DNA cleavage; this factor comprises DFF45 and DFF40
      subunits, the former of which acts as a chaperone and inhibitor of the catalytic
      subunit and whose cleavage by caspase-3 results in DFF activation. Disruption of
      the DFF45 gene blocks internucleosomal DNA fragmentation and confers resistance
      to apoptosis in primary thymocytes. The role of DFF-mediated DNA fragmentation in
      apoptosis was investigated in primary fibroblasts from DFF45(-/-) and control
      (DFF45(+/+)) mice. DFF45 deficiency rendered fibroblasts resistant to apoptosis
      induced by tumor necrosis factor (TNF). TNF induced rapid cleavage of DNA into
      approximately 50-kb fragments in DFF45(+/+) fibroblasts but not in DFF45(-/-)
      cells, indicating that DFF mediates this initial step in DNA processing. The TNF
      induced activation of poly(ADP-ribose) polymerase (PARP), which requires PARP
      binding to DNA strand breaks, and the consequent depletion of the PARP substrate
      NAD were markedly delayed in DFF45(-/-) cells, suggesting a role for DFF in PARP
      activation. The activation of caspase-3 and mitochondrial events important in
      apoptotic signaling, including the loss of mitochondrial membrane potential and
      the release of cytochrome c, induced by TNF were similarly delayed in DFF45(-/-)
      fibroblasts. DFF45(-/-) and DFF45(+/+) cells were equally sensitive to the DNA
      damaging agent and PARP activator N-methyl-N'-nitro-N-nitrosoguanidine.
      Inhibition of PARP by 3-aminobenzamide partially protected DFF45(+/+) cells
      against TNF-induced death and inhibited the associated release of cytochrome c
      and activation of caspase-3. These results suggest that the generation of 50-kb
      DNA fragments by DFF, together with the activation of PARP, mitochondrial
      dysfunction, and caspase-3 activation, contributes to an amplification loop in
      the death process.

PMID- 11461901
TI  - Maf and Jun nuclear oncoproteins share downstream target genes for inducing cell
      transformation.
AB  - The Maf oncoprotein is a basic leucine zipper (bZip)-bearing transcriptional
      activator that recognizes the Maf recognition element (MARE) DNA sequence. In
      this study, we investigated the role of Maf's transactivation function in cell
      transformation. Replacement of the conserved amino terminus transactivator domain
      of Maf by a heterologous and stronger transactivator domain (the acidic
      transactivator domain of VP16) resulted in enhanced transformation of chicken
      embryo fibroblast cells. In contrast, the fusing of a transcriptional repressor
      domain (Sin3 interaction domain of Mxi1) with the whole Maf protein masked the
      transactivator function of Maf, which in turn inhibited its transforming
      activity. Furthermore, the leucine zipper domain of Maf, which defines its dimer
      forming specificity, was exchangeable with that of GCN4 yeast protein in terms of
      its transactivating and cell transforming activities. Thus, heterodimer formation
      with other bZip factors is not required for Maf's ability to transform. These
      results together suggest that transactivation through MARE is necessary for Maf
      induced transformation and that there exist downstream target gene(s) for
      transformation. Since the MARE sequence overlaps with the recognition element of
      another bZip oncoprotein Jun, we assessed whether Jun and Maf induce cell
      transformation through activating the same genes. We thus constructed a mutated
      version of Jun that has a GCN4 leucine zipper and lacks the transactivator
      domain. This mutant repressed the cell transformation not only by Jun but also by
      Maf. Thus, Maf and Jun share downstream target gene(s) that are involved in cell
      transformation.

PMID- 11461902
TI  - 1alpha,25-Dihydroxyvitamin D3-induced monocyte antimycobacterial activity is
      regulated by phosphatidylinositol 3-kinase and mediated by the NADPH-dependent
      phagocyte oxidase.
AB  - We investigated the basis for the induction of monocyte antimycobacterial
      activity by 1alpha,25-dihydroxyvitamin D(3) (D(3)). As expected, incubation of
      Mycobacterium tuberculosis-infected THP-1 cells or human peripheral blood,
      monocyte-derived macrophages with hormone resulted in the induction of
      antimycobacterial activity. This effect was significantly abrogated by
      pretreatment of cells with either of the phosphatidylinositol 3-kinase (PI 3-K)
      inhibitors, wortmannin or LY294002, or with antisense oligonucleotides to the
      p110 subunit of PI 3-Kalpha. Cells infected with M. tuberculosis alone or
      incubated with D(3) alone produced little or undetectable amounts of superoxide
      anion (O(2)). In contrast, exposure of M. tuberculosis-infected cells to D(3) led
      to significant production of O(2), and this response was eliminated by either
      wortmannin, LY294002, or p110 antisense oligonucleotides. As was observed for PI
      3-K inactivation, the reactive oxygen intermediate scavenger, 4-hydroxy-TEMPO,
      and degradative enzymes, polyethylene glycol coupled to either superoxide
      dismutase or catalase, also abrogated D(3)-induced antimycobacterial activity.
      Superoxide production by THP-1 cells in response to D(3) required prior infection
      with live M. tuberculosis, since exposure of cells to either killed M.
      tuberculosis or latex beads did not prime for an oxidative burst in response to
      subsequent hormone treatment. Consistent with these findings, redistribution of
      the cytosolic oxidase components p47(phox) and p67(phox) to the membrane fraction
      was observed in cells incubated with live M. tuberculosis and D(3) but not in
      response to combined treatment with heat-killed M. tuberculosis followed by D(3).
      Redistribution of p47(phox) and p67(phox) to the membrane fraction in response to
      live M. tuberculosis and D(3) was also abrogated under conditions where PI 3-K
      was inactivated. Taken together, these results indicate that D(3)-induced, human
      monocyte antimycobacterial activity is regulated by PI 3-K and mediated by the
      NADPH-dependent phagocyte oxidase.

PMID- 11461903
TI  - The phytochrome A-specific signaling intermediate SPA1 interacts directly with
      COP1, a constitutive repressor of light signaling in Arabidopsis.
AB  - SPA1 is a phytochrome A (phyA)-specific signaling intermediate that acts as a
      light-dependent repressor of photomorphogenesis in Arabidopsis seedlings. It
      contains a WD-repeat domain that shows high sequence similarity to the WD-repeat
      region of the constitutive repressor of light signaling, COP1. Here, using yeast
      two-hybrid and in vitro interaction assays, we show that SPA1 strongly and
      selectively binds to COP1. Domain mapping studies indicate that the putative
      coiled-coil domain of SPA1 is necessary and sufficient for binding to COP1.
      Conversely, similar deletion analyses of the COP1 protein suggest that SPA1
      interacts with the presumed coiled-coil domain of COP1. To further investigate
      SPA1 function in the phyA signaling pathway, we tested whether SPA1, like COP1,
      mediates changes in gene expression in response to light. We show that spa1
      mutations increase the photoresponsiveness of certain light-regulated genes
      within 2 h of light treatment. Taken together, the results suggest that SPA1 may
      function to link the phytochrome A-specific branch of the light signaling pathway
      to COP1. Hence, our data provide molecular support for the hypothesis that COP1
      is a convergence point for upstream signaling pathways dedicated to individual
      photoreceptors.

PMID- 11461904
TI  - Pro-survival function of Akt/protein kinase B in prostate cancer cells.
      Relationship with TRAIL resistance.
AB  - Tumor necrosis factor superfamily member TRAIL/Apo-2L has recently been shown to
      induce apoptosis in transformed and cancer cells. Some prostate cancer cells
      express constitutively active Akt/protein kinase B due to a complete loss of
      lipid phosphatase PTEN gene, a negative regulator of phosphatidylinositol 3
      kinase pathway. Constitutively active Akt promotes cellular survival and
      resistance to chemotherapy and radiation. We have recently noticed that some
      human prostate cancer cells are resistant to TRAIL. We therefore examined the
      intracellular mechanisms of cellular resistance to TRAIL. The cell lines
      expressing the highest level of constitutively active Akt were more resistant to
      undergo apoptosis by TRAIL than those expressing the lowest level. Down
      regulation of constitutively active Akt by phosphatidylinositol 3-kinase
      inhibitors, wortmannin and LY294002, reversed cellular resistance to TRAIL.
      Treatment of resistant cells with cycloheximide (a protein synthesis inhibitor)
      rendered cells sensitive to TRAIL. Transfecting dominant negative Akt decreased
      Akt activity and increased TRAIL-induced apoptosis in cells with high Akt
      activity. Conversely, transfecting constitutively active Akt into cells with low
      Akt activity increased Akt activity and attenuated TRAIL-induced apoptosis.
      Inhibition of TRAIL sensitivity occurs at the level of BID cleavage, as caspase-8
      activity was not affected. Enforced expression of anti-apoptotic protein Bcl-2 or
      Bcl-X(L) inhibited TRAIL-induced mitochondrial dysfunction and apoptosis. We
      therefore identify Akt as a constitutively active kinase that promotes survival
      of prostate cancer cells and demonstrate that modulation of Akt activity, by
      pharmacological or genetic approaches, alters the cellular responsiveness to
      TRAIL. Thus, TRAIL in combination with agents that down-regulate Akt activity can
      be used to treat prostate cancer.

PMID- 11461905
TI  - The phosphatase C(X)5R motif is required for catalytic activity of the
      Saccharomyces cerevisiae Acr2p arsenate reductase.
AB  - Acr2p detoxifies arsenate by reduction to arsenite in Saccharomyces cerevisiae.
      This reductase has been shown to require glutathione and glutaredoxin, suggesting
      that thiol chemistry might be involved in the reaction mechanism. Acr2p has a
      HC(X)(5)R motif, the signature sequence of the phosphate binding loop of the dual
      specific and protein-tyrosine phosphatase family. In Acr2p these are residues His
      75, Cys-76, and Arg-82, respectively. Acr2p has another sequence, (118)HCR, that
      is absent in phosphatases. Acr2p also has a third cysteine residue at position
      106. Each of these cysteine residues was changed individually to serine residues,
      whereas the histidine and arginine residues were altered to alanines. Cells of
      Escherichia coli heterologously expressing the majority of the mutant ACR2 genes
      retained wild type resistance to arsenate, and the purified altered Acr2p
      proteins exhibited normal enzymatic properties. In contrast, cells expressing
      either the C76S or R82A mutations lost resistance to arsenate, and the purified
      proteins were inactive. These results suggest that Acr2p utilizes a phosphatase
      like Cys(X)(5)Arg motif as the catalytic center to reduce arsenate to arsenite.

PMID- 11461906
TI  - Enhanced gluconeogenesis and increased energy storage as hallmarks of aging in
      Saccharomyces cerevisiae.
AB  - A relationship between life span and cellular glucose metabolism has been
      inferred from genetic manipulations and caloric restriction of model organisms.
      In this report, we have used the Snf1p glucose-sensing pathway of Saccharomyces
      cerevisiae to explore the genetic and biochemical linkages between glucose
      metabolism and aging. Snf1p is a serine/threonine kinase that regulates cellular
      responses to glucose deprivation. Loss of Snf4p, an activator of Snf1p, extends
      generational life span whereas loss of Sip2p, a presumed repressor of the kinase,
      causes an accelerated aging phenotype. An annotated data base of global age
      associated changes in gene expression in isogenic wild-type, sip2Delta, and
      snf4Delta strains was generated from DNA microarray studies. The transcriptional
      responses suggested that gluconeogenesis and glucose storage increase as wild
      type cells age, that this metabolic evolution is exaggerated in rapidly aging
      sip2Delta cells, and that it is attenuated in longer-lived snf4Delta cells. To
      test this hypothesis directly, we applied microanalytic biochemical methods to
      generation-matched cells from each strain and measured the activities of enzymes
      and concentrations of metabolites in the gluconeogenic, glycolytic, and
      glyoxylate pathways, as well as glycogen, ATP, and NAD(+). The sensitivity of the
      assays allowed comprehensive biochemical profiling to be performed using aliquots
      of the same cell populations employed for the transcriptional profiling. The
      results provided additional evidence that aging in S. cerevisiae is associated
      with a shift away from glycolysis and toward gluconeogenesis and energy storage.
      They also disclosed that this shift is forestalled by two manipulations that
      extend life span, caloric restriction and genetic attenuation of the normal age
      associated increase in Snf1p activity. Together, these findings indicate that
      Snf1p activation is not only a marker of aging but also a candidate mediator,
      because a shift toward energy storage over expenditure could impact myriad
      aspects of cellular maintenance and repair.

PMID- 11461907
TI  - Interleukin-8 up-regulation by neutrophil elastase is mediated by MyD88/IRAK/TRAF
      6 in human bronchial epithelium.
AB  - Cystic fibrosis is characterized in the lungs by neutrophil-dominated
      inflammation mediated significantly by neutrophil elastase (NE). Previous work
      has shown that NE induces interleukin-8 (IL-8) gene expression and protein
      secretion in bronchial epithelial cells. We sought to determine the intracellular
      mechanisms by which NE up-regulates IL-8 in bronchial epithelial cells. The data
      show that stimulation of 16HBE14o(-) cells with NE induced IL-8 protein
      production and gene expression. Both responses were abrogated by actinomycin D,
      indicating that regulation is at the transcriptional level. Electrophoretic
      mobility shift assays demonstrated that nuclear factor kappaB (NFkappaB) was
      activated in 16HBE14o(-) cells stimulated with NE. Western blot analysis
      demonstrated that activation of NFkappaB by NE was preceded by phosphorylation
      and degradation of IkappaB proteins, principally IkappaBbeta. In addition, we
      observed that interleukin-1 receptor-associated kinase (IRAK) was degraded in
      16HBE14o(-) cells stimulated with NE. Quantification of IL-8 reporter gene
      activity by luminometry demonstrated that dominant negative MyD88 (MyD88Delta) or
      TRAF-6 (TRAF-6Delta) inhibited IL-8 reporter gene expression in response to NE.
      Furthermore, MyD88Delta inhibited NE-induced IRAK degradation. These results show
      that NE induces IL-8 gene up-regulation in bronchial epithelial cells through an
      IRAK signaling pathway involving both MyD88 and TRAF-6, resulting in degradation
      of IkappaBbeta and nuclear translocation of NFkappaB. These findings may have
      implications for therapeutic treatments in the cystic fibrosis condition.

PMID- 11461908
TI  - Coordinated agonist regulation of receptor and G protein palmitoylation and
      functional rescue of palmitoylation-deficient mutants of the G protein G11alpha
      following fusion to the alpha1b-adrenoreceptor: palmitoylation of G11alpha is not
      required for interaction with beta*gamma complex.
AB  - Transfection of either the alpha(1b)-adrenoreceptor or Galpha(11) into a
      fibroblast cell line derived from a Galpha(q)/Galpha(11) double knockout mouse
      failed to produce elevation of intracellular [Ca(2+)] upon the addition of
      agonist. Co-expression of these two polypeptides, however, produced a significant
      stimulation. Co-transfection of the alpha(1b)-adrenoreceptor with the
      palmitoylation-resistant C9S,C10S Galpha(11) also failed to produce a signal, and
      much reduced and kinetically delayed signals were obtained using either C9S
      Galpha(11) or C10S Galpha(11). Expression of a fusion protein between the
      alpha(1b)-adrenoreceptor and Galpha(11) allowed [Ca(2+)](i) elevation, and this
      was also true for a fusion protein between the alpha(1b)-adrenoreceptor and
      C9S,C10S Galpha(11), since this strategy ensures proximity of the two
      polypeptides at the cell membrane. For both fusion proteins, co-expression of
      transducin alpha, as a beta.gamma-sequestering agent, fully attenuated the Ca(2+)
      signal. Both of these fusion proteins and one in which an acylation-resistant
      form of the receptor was linked to wild type Galpha(11) were also targets for
      agonist-regulated [(3)H]palmitoylation and bound [(35)S]guanosine 5'-3-O
      (thio)triphosphate (GTPgammaS) in an agonist concentration-dependent manner. The
      potency of agonist to stimulate [(35)S]GTPgammaS binding was unaffected by the
      palmitoylation potential of either receptor or G protein. These studies provide
      clear evidence for coordinated, agonist-mediated regulation of the post
      translational acylation of both a receptor and partner G protein and demonstrate
      the capacity of such fusions to bind and then release beta.gamma complex upon
      agonist stimulation whether or not the G protein can be palmitoylated. They also
      demonstrate that Ca(2+) signaling in EF88 cells by such fusion proteins is
      mediated via release of the G protein beta.gamma complex.

PMID- 11461909
TI  - Spatial-temporal patterning of metabotropic glutamate receptor-mediated inositol
      1,4,5-triphosphate, calcium, and protein kinase C oscillations: protein kinase C
      dependent receptor phosphorylation is not required.
AB  - The metabotropic glutamate receptors (mGluR), mGluR1a and mGluR5a, are G protein
      coupled receptors that couple via G(q) to the hydrolysis of phosphoinositides,
      the release of Ca(2+) from intracellular stores, and the activation of protein
      kinase C (PKC). We show here that mGluR1/5 activation results in oscillatory G
      protein coupling to phospholipase C thereby stimulating oscillations in both
      inositol 1,4,5-triphosphate formation and intracellular Ca(2+) concentrations.
      The mGluR1/5-stimulated Ca(2+) oscillations are translated into the synchronized
      repetitive redistribution of PKCbetaII between the cytosol and plasma membrane.
      The frequency at which mGluR1a and mGluR5a subtypes stimulate inositol 1,4,5
      triphosphate, Ca(2+), and PKCbetaII oscillations is regulated by the charge of a
      single amino acid residue localized within their G protein-coupling domains.
      However, oscillatory mGluR signaling does not involve the repetitive feedback
      phosphorylation and desensitization of mGluR activity, since mutation of the
      putative PKC consensus sites within the first and second intracellular loops as
      well as the carboxyl-terminal tail does not prevent mGluR1a-stimulated PKCbetaII
      oscillations. Furthermore, oscillations in Ca(2+) continued in the presence of
      PKC inhibitors, which blocked PKCbetaII redistribution from the plasma membrane
      back into the cytosol. We conclude that oscillatory mGluR signaling represents an
      intrinsic receptor/G protein coupling property that does not involve PKC feedback
      phosphorylation.

PMID- 11461910
TI  - The Notch intracellular domain is ubiquitinated and negatively regulated by the
      mammalian Sel-10 homolog.
AB  - The Caenorhabditis elegans sel-10 protein is structurally similar to E3 ubiquitin
      ligases and is a negative regulator of Notch (lin-12) and presenilin signaling.
      In this report, we characterize the mammalian Sel-10 homolog (mSel-10) and
      analyze its effects on Notch signaling. We find that mSel-10 localizes to the
      cell nucleus, and that it physically interacts with the Notch 1 intracellular
      domain (IC) and reduces Notch 1 IC-mediated activation of the HES 1 promoter.
      Notch 1 IC is ubiquitinated by mSel-10, and ubiquitination requires the presence
      of the most carboxyl-terminal region of the Notch IC, including the PEST domain.
      In the presence of the proteasome inhibitor MG132, the amount of Notch 1 IC and
      its level of ubiquitination are increased. Interestingly, this accumulation of
      Notch 1 IC in the presence of MG132 is accompanied by decreased activation of the
      HES 1 promoter, suggesting that ubiquitinated Notch 1 IC is a less potent
      transactivator. Finally, we show that mSel-10 itself is ubiquitinated and
      degraded by the proteasome. In conclusion, these data reveal the importance of
      ubiquitination and proteasome-mediated degradation for the activity and turnover
      of Notch ICs, and demonstrate that mSel-10 plays a key role in this process.

PMID- 11461911
TI  - Hepatitis B virus X protein differentially activates RAS-RAF-MAPK and JNK
      pathways in X-transforming versus non-transforming AML12 hepatocytes.
AB  - The hepatitis B virus (HBV) X protein (pX) is implicated in hepatocarcinogenesis
      of chronic HBV patients by an unknown mechanism. Activities of pX likely relevant
      to hepatocyte transformation include activation of the mitogenic RAS-RAF-MAPK and
      JNK pathways. To assess the importance of mitogenic pathway activation by pX in
      transformation, we employed a cellular model system composed of two tetracycline
      regulated, pX-expressing cell lines, constructed in AML12-immortalized
      hepatocytes. This system includes the differentiated 3pX-1 and the de
      differentiated 4pX-1 hepatocytes. Our studies have demonstrated that conditional
      pX expression transforms only 3pX-1 cells. Here, comparative in vitro kinase
      assays and various in vivo analyses demonstrate that pX affects an inverse
      activation of RAS-RAF-MAPK and JNK pathways in 3pX-1 versus 4pX-1 cells.
      Sustained pX-dependent RAS-RAF-MAPK pathway activation is observed in pX
      transforming 3pX-1 cells, whereas sustained pX-dependent JNK pathway activation
      is observed in pX non-transforming 4pX-1 cells. This differential, pX-dependent
      mitogenic pathway activation affects differential activation of cAMP-response
      element-binding protein and c-Jun and determines the proliferative response of
      3pX-1 and 4pX-1 cells. Furthermore, tetracycline-regulated, pX-NLS-expressing
      cell lines demonstrate that expression of the nuclear pX-NLS variant minimally
      activates the RAS-RAF-MAPK pathway and results in markedly reduced
      transformation. These results link sustained, pX-mediated activation of RAS-RAF
      MAPK pathway to hepatocyte transformation.

PMID- 11461912
TI  - Copper,zinc superoxide dismutase as a univalent NO(-) oxidoreductase and as a
      dichlorofluorescin peroxidase.
AB  - Nitroxyl (NO(-)) may be produced by nitric-oxide synthase and by the reduction of
      NO by reduced Cu,Zn-SOD. The ability of NO(-) to cause oxidations and of SOD to
      inhibit such oxidations was therefore explored. The decomposition of Angeli's
      salt (AS) produces NO(-) and that in turn caused the aerobic oxidation of NADPH,
      directly or indirectly. O(2) was produced concomitant with the aerobic oxidation
      of NADPH by AS, as evidenced by the SOD-inhibitable reduction of cytochrome c.
      Both Cu,Zn-SOD and Mn-SOD inhibited the aerobic oxidation of NADPH by AS, but the
      amounts required were approximately 100-fold greater than those needed to inhibit
      the reduction of cytochrome c. This inhibition was not due to a nonspecific
      protein effect or to an effect of those large amounts of the SODs on the rate of
      decomposition of AS. NO(-) caused the reduction of the Cu(II) of Cu,Zn-SOD, and
      in the presence of O(2), SOD could catalyze the oxidation of NO(-) to NO. The
      reverse reaction, i.e. the reduction of NO to NO(-) by Cu(I),Zn-SOD, followed by
      the reaction of NO(-) with O(2) would yield ONOO(-) and that could explain the
      oxidation of dichlorofluorescin (DCF) by Cu(I),Zn-SOD plus NO. Cu,Zn-SOD plus
      H(2)O(2) caused the HCO(3)(-)-dependent oxidation of DCF, casting doubt on the
      validity of using DCF oxidation as a reliable measure of intracellular H(2)O(2)
      production.

PMID- 11461913
TI  - Functional characterization of Pactolus, a beta-integrin-like protein
      preferentially expressed by neutrophils.
AB  - Murine Pactolus is a beta-integrin-like molecule expressed exclusively on the
      surface of granulocytes. Cell surface expression of Pactolus is dramatically
      increased following activation of bone marrow neutrophils with known agonists,
      and cross-linking of cell surface Pactolus, suggesting the bulk of the protein is
      in intracellular stores. The mature protein is found in two forms depending upon
      the extent of N-linked glycosylation. There is no evidence to suggest that
      Pactolus requires an associated alpha chain for expression. In some mouse
      strains, a truncated form of the protein is predicted based upon alternative
      splicing: this form, however, is unstable and rapidly degraded after synthesis.
      Differences in the quantities of these Pactolus mRNA isoforms have defined two
      alleles. BALB/c and C3H/HeJ mice possess allele B and preferentially express the
      truncated, unstable product, whereas C57BL/6 mice possess allele A and only
      produce the membrane-bound form. Sequence analysis has shown the difference
      between these two alleles is due to a single base pair difference at the splice
      acceptor site for the truncated product. The increased expression of the membrane
      form of Pactolus by granulocytes of C57BL/6 mice suggests a compensatory adhesion
      function that is reduced in cells from the low producing strains.

PMID- 11461914
TI  - Identification of peptide ligand-binding domains within the human motilin
      receptor using photoaffinity labeling.
AB  - The cDNA encoding the human motilin receptor was recently cloned and found to
      represent a G protein-coupled receptor that is structurally related to the growth
      hormone secretagogue receptors. Together, these represent a new Class I receptor
      family. Our aim in the present work is to gain insight into the molecular basis
      of binding of motilin to its receptor using photoaffinity labeling. To achieve
      this, we developed a Chinese hamster ovary cell line that overexpressed
      functional motilin receptor (CHO-MtlR; 175,000 sites per cell, with K(i) = 2.3 +/
      0.4 nm motilin and EC(50) = 0.3 +/- 0.1 nm motilin) and a radioiodinatable
      peptide analogue of human motilin that incorporated a photolabile p-benzoyl-l
      phenylalanine (Bpa) residue into its pharmacophoric domain. This probe,
      [Bpa(1),Ile(13)]motilin, was a full agonist at the motilin receptor that
      increased intracellular calcium in a concentration-dependent manner (EC(50) = 1.5
      +/- 0.4 nm). This photolabile ligand bound specifically and with high affinity to
      the motilin receptor (K(i) = 12.4 +/- 1.0 nm), and covalently labeled that
      molecule within its M(r) = 45,000 deglycosylated core. Cyanogen bromide cleavage
      demonstrated its covalent attachment to fragments of the receptor having apparent
      M(r) = 6,000 and M(r) = 31,000. These were demonstrated to represent fragments
      that included both the first and the large second extracellular loop domains,
      with the latter representing a unique structural feature of this receptor. The
      spatial approximation of the pharmacophoric domain of motilin with these receptor
      domains support their functional importance as well.

PMID- 11461915
TI  - Identification of the carbohydrate moieties and glycosylation motifs in
      Campylobacter jejuni flagellin.
AB  - Flagellins from three strains of Campylobacter jejuni and one strain of
      Campylobacter coli were shown to be extensively modified by glycosyl residues,
      imparting an approximate 6000-Da shift from the molecular mass of the protein
      predicted from the DNA sequence. Tryptic peptides from C. jejuni 81-176 flagellin
      were subjected to capillary liquid chromatography-electrospray mass spectrometry
      with a high/low orifice stepping to identify peptide segments of aberrant masses
      together with their corresponding glycosyl appendages. These modified peptides
      were further characterized by tandem mass spectrometry and preparative high
      performance liquid chromatography followed by nano-NMR spectroscopy to identify
      the nature and precise site of glycosylation. These analyses have shown that
      there are 19 modified Ser/Thr residues in C. jejuni 81-176 flagellin. The
      predominant modification found on C. jejuni flagellin was O-linked 5,7
      diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-nonulosonic acid (pseudaminic
      acid, Pse5Ac7Ac) with additional heterogeneity conferred by substitution of the
      acetamido groups with acetamidino and hydroxyproprionyl groups. In C. jejuni 81
      176, the gene Cj1316c, encoding a protein of unknown function, was shown to be
      involved in the biosynthesis and/or the addition of the acetamidino group on
      Pse5Ac7Ac. Glycosylation is not random, since 19 of the total 107 Ser/Thr
      residues are modified, and all but one of these are restricted to the central,
      surface-exposed domain of flagellin when folded in the filament. The mechanism of
      attachment appears unrelated to a consensus peptide sequence but is rather based
      on surface accessibility of Ser/Thr residues in the folded protein.

PMID- 11461916
TI  - Differential regulation of Cdc2 and Cdk2 by RINGO and cyclins.
AB  - Cyclin-dependent kinases (Cdks) are key regulators of the eukaryotic cell
      division cycle. Cdk1 (Cdc2) and Cdk2 should be bound to regulatory subunits named
      cyclins as well as phosphorylated on a conserved Thr located in the T-loop for
      full enzymatic activity. Cdc2- and Cdk2-cyclin complexes can be inactivated by
      phosphorylation on the catalytic cleft-located Thr-14 and Tyr-15 residues or by
      association with inhibitory subunits such as p21(Cip1). We have recently
      identified a novel Cdc2 regulator named RINGO that plays an important role in the
      meiotic cell cycle of Xenopus oocytes. RINGO can bind and activate Cdc2 but has
      no sequence homology to cyclins. Here we report that, in contrast with Cdc2-
      cyclin complexes, the phosphorylation of Thr-161 is not required for full
      activation of Cdc2 by RINGO. We also show that RINGO can directly stimulate the
      kinase activity of Cdk2 independently of Thr-160 phosphorylation. Moreover, RINGO
      bound Cdc2 and Cdk2 are both less susceptible to inhibition by p21(Cip1), whereas
      the Thr-14/Tyr-15 kinase Myt1 can negatively regulate the activity of Cdc2-RINGO
      with reduced efficiency. Our results indicate that Cdk-RINGO complexes may be
      active under conditions in which cyclin-bound Cdks are inhibited and can
      therefore play different regulatory roles.

PMID- 11461917
TI  - DNA sequence plays a major role in determining nucleosome positions in yeast CUP1
      chromatin.
AB  - The role of DNA sequence in determining nucleosome positions in vivo was
      investigated by comparing the positions adopted by nucleosomes reconstituted on a
      yeast plasmid in vitro using purified core histones with those in native
      chromatin containing the same DNA, described previously. Nucleosomes were
      reconstituted on a 2.5 kilobase pair DNA sequence containing the yeast TRP1ARS1
      plasmid with CUP1 as an insert (TAC-DNA). Multiple, alternative, overlapping
      nucleosome positions were mapped on TAC-DNA. For the 58 positioned nucleosomes
      identified, the relative positioning strengths and the stabilities to salt and
      temperature were determined. These positions were, with a few exceptions,
      identical to those observed in native, remodeled TAC chromatin containing an
      activated CUP1 gene. Only some of these positions are utilized in native,
      unremodeled chromatin. These observations suggest that DNA sequence is likely to
      play a very important role in positioning nucleosomes in vivo. We suggest that
      events occurring in yeast CUP1 chromatin determine which positions are occupied
      in vivo and when they are occupied.

PMID- 11461918
TI  - Activation of myosin light chain phosphatase in intact arterial smooth muscle
      during nitric oxide-induced relaxation.
AB  - We investigated whether myosin light chain phosphatase activity changes during
      nitric oxide-induced relaxation of contracted intact carotid media and how
      changes in phosphatase activity mediate this relaxation. We also investigated one
      mechanism for regulating this phosphatase. Myosin phosphatase activity, myosin
      light chain phosphorylation, guanosine 3',5'-cyclic monophosphate (cGMP)
      concentration, and phosphorylation of the inhibitory protein CPI-17 were all
      assayed in homogenates of one carotid media ring at each time point during nitric
      oxide-induced relaxation. The application of sodium nitroprusside to histamine
      contracted media caused rapid declines in light chain phosphorylation and force.
      These were temporally correlated with a rapid elevation of cGMP and a large
      transient increase in myosin phosphatase activity. During the early response to
      nitroprusside, when force declined, increases in myosin phosphatase activity,
      concurrent with cGMP-mediated decreases in calcium and myosin light chain kinase
      activity, could accelerate light chain dephosphorylation. CPI-17 was
      dephosphorylated upon application of nitroprusside at the same time that myosin
      phosphatase activity increased, suggesting that the removal of inhibition by
      phospho-CPI-17 contributed to the increase in myosin phosphatase activity. After
      20 min of nitroprusside, myosin phosphatase activity had declined to basal
      levels, however low force was sustained. Additional light chain phosphorylation
      independent mechanisms may be involved in sustaining the relaxation.

PMID- 11461919
TI  - Alternative splicing determines the function of CYP4F3 by switching substrate
      specificity.
AB  - Diversity of cytochrome P450 function is determined by the expression of multiple
      genes, many of which have a high degree of identity. We report that the use of
      alternate exons, each coding for 48 amino acids, generates isoforms of human
      CYP4F3 that differ in substrate specificity, tissue distribution, and biological
      function. Both isoforms contain a total of 520 amino acids. CYP4F3A, which
      incorporates exon 4, inactivates LTB4 by omega-hydroxylation (Km = 0.68 microm)
      but has low activity for arachidonic acid (Km = 185 microm); it is the only CYP4F
      isoform expressed in myeloid cells in peripheral blood and bone marrow. CYP4F3B
      incorporates exon 3 and is selectively expressed in liver and kidney; it is also
      the predominant CYP4F isoform in trachea and tissues of the gastrointestinal
      tract. CYP4F3B has a 30-fold higher Km for LTB4 compared with CYP4F3A, but it
      utilizes arachidonic acid as a substrate for omega-hydroxylation (Km = 22 microm)
      and generates 20-HETE, an activator of protein kinase C and Ca2+/calmodulin
      dependent kinase II. Homology modeling demonstrates that the alternative exon has
      a position in the molecule which could enable it to contribute to substrate
      interactions. The results establish that tissue-specific alternative splicing of
      pre-mRNA can be used as a mechanism for changing substrate specificity and
      increasing the functional diversity of cytochrome P450 genes.

PMID- 11461920
TI  - beta III spectrin binds to the Arp1 subunit of dynactin.
AB  - Cytoplasmic dynein is an intracellular motor responsible for endoplasmic
      reticulum-to-Golgi vesicle trafficking and retrograde axonal transport. The
      accessory protein dynactin has been proposed to mediate the association of dynein
      with vesicular cargo. Dynactin contains a 37-nm filament made up of the actin
      related protein, Arp1, which may interact with a vesicle-associated spectrin
      network. Here, we demonstrate that Arp1 binds directly to the Golgi-associated
      betaIII spectrin isoform. We identify two Arp1-binding sites in betaIII spectrin,
      one of which overlaps with the actin-binding site conserved among spectrins.
      Although conventional actin binds weakly to betaIII spectrin, Arp1 binds robustly
      in the presence of excess F-actin. Dynein, dynactin, and betaIII spectrin co
      purify on vesicles isolated from rat brain, and betaIII spectrin co
      immunoprecipitates with dynactin from rat brain cytosol. In interphase cells,
      betaIII spectrin and dynactin both localize to cytoplasmic vesicles, co
      localizing most significantly in the perinuclear region of the cell. In dividing
      cells, betaIII spectrin and dynactin co-localize to the developing cleavage
      furrow and mitotic spindle, a novel localization for betaIII spectrin. We
      hypothesize that the interaction between betaIII spectrin and Arp1 recruits
      dynein and dynactin to intracellular membranes and provides a direct link between
      the microtubule motor complex and its membrane-bounded cargo.

PMID- 11461921
TI  - Interactions of fibrillin-1 with heparin/heparan sulfate, implications for
      microfibrillar assembly.
AB  - Fibrillin-1 is a major constituent of the 10-12 nm extracellular microfibrils.
      Here we identify, characterize, and localize heparin/heparan sulfate-binding
      sites in fibrillin-1 and report on the role of such glycosaminoglycans in the
      assembly of fibrillin-1. By using different binding assays, we localize two
      calcium-independent heparin-binding sites to the N-terminal (Arg(45)-Thr(450))
      and C-terminal (Asp(1528)-Arg(2731)) domains of fibrillin-1. A calcium-dependent
      binding site was localized to the central (Asp(1028)-Thr(1486)) region of
      fibrillin-1. Heparin binding to these sites can be inhibited by a highly sulfated
      and iduronated form of heparan sulfate but not by chondroitin 4-sulfate,
      chondroitin 6-sulfate, and dermatan sulfate, demonstrating that the heparin
      binding regions represent binding domains for heparan sulfate. When heparin or
      heparan sulfate was added to cultures of skin fibroblasts, the assembly of
      fibrillin-1 into a microfibrillar network was significantly reduced. Western blot
      analysis demonstrated that this effect was not due to a reduced amount of
      fibrillin-1 secreted into the culture medium. Inhibition of the attachment of
      glycosaminoglycans to core proteins of proteoglycans by beta-d-xylosides resulted
      in a significant reduction of the fibrillin-1 network. These studies suggest that
      binding of fibrillin-1 to proteoglycan-associated heparan sulfate chains is an
      important step in the assembly of microfibrils.

PMID- 11461922
TI  - Nitric oxide inhibits ornithine decarboxylase via S-nitrosylation of cysteine 360
      in the active site of the enzyme.
AB  - Ornithine decarboxylase is the initial and rate-limiting enzyme in the polyamine
      biosynthetic pathway. Polyamines are found in all mammalian cells and are
      required for cell growth. We previously demonstrated that N-hydroxyarginine and
      nitric oxide inhibit tumor cell proliferation by inhibiting arginase and
      ornithine decarboxylase, respectively, and, therefore, polyamine synthesis. In
      addition, we showed that nitric oxide inhibits purified ornithine decarboxylase
      by S-nitrosylation. Herein we provide evidence for the chemical mechanism by
      which nitric oxide and S-nitrosothiols react with cysteine residues in ornithine
      decarboxylase to form an S-nitrosothiol(s) on the protein. The diazeniumdiolate
      nitric oxide donor agent 1-diethyl-2-hydroxy-2-nitroso-hydrazine acts through an
      oxygen-dependent mechanism leading to formation of the nitrosating agents
      N(2)O(3) and/or N(2)O(4). S-Nitrosoglutathione inhibits ornithine decarboxylase
      by an oxygen-independent mechanism likely by S-transnitrosation. In addition, we
      provide evidence for the S-nitrosylation of 4 cysteine residues per ornithine
      decarboxylase monomer including cysteine 360, which is critical for enzyme
      activity. Finally S-nitrosylated ornithine decarboxylase was isolated from intact
      cells treated with nitric oxide, suggesting that nitric oxide may regulate
      ornithine decarboxylase activity by S-nitrosylation in vivo.

PMID- 11461923
TI  - Temporal translational control by a metastable RNA structure.
AB  - Programmed cell death by the hok/sok locus of plasmid R1 relies on a complex
      translational control mechanism. The highly stable hok mRNA is activated by 3'
      end exonucleolytical processing. Removal of the mRNA 3' end releases a 5'-end
      sequence that triggers refolding of the mRNA. The refolded hok mRNA is
      translatable but can also bind the inhibitory Sok antisense RNA. Binding of Sok
      RNA leads to irreversible mRNA inactivation by an RNase III-dependent mechanism.
      A coherent model predicts that during transcription hok mRNA must be refractory
      to translation and antisense RNA binding. Here we provide genetic evidence for
      the existence of a 5' metastable structure in hok mRNA that locks the nascent
      transcript in an inactive configuration in vivo. Consistently, the metastable
      structure reduces the rate of Sok RNA binding and completely blocks hok
      translation in vitro. Structural analyses of native RNAs strongly support that
      the 5' metastable structure exists in the nascent transcript. Further structural
      analyses reveal that the mRNA 3' end triggers refolding of the mRNA 5' end into
      the more stable tac-stem conformation. These results provide a profound
      understanding of an unusual and intricate post-transcriptional control mechanism.

PMID- 11461924
TI  - Copper transport and metabolism are normal in aceruloplasminemic mice.
AB  - Ceruloplasmin is an abundant serum glycoprotein containing greater than 95% of
      the copper found in the plasma of vertebrate species. Although this protein is
      known to function as an essential ferroxidase, the role of ceruloplasmin in
      copper transport and metabolism remains unclear. To elucidate the role of
      ceruloplasmin in copper metabolism, the kinetics of copper absorption, transport,
      distribution, and excretion were examined utilizing (64)Cu in wild-type and
      aceruloplasminemic mice. No differences in gastrointestinal absorption, hepatic
      uptake, or biliary excretion were observed in these animals. Furthermore, steady
      state measurements of tissue copper content utilizing (64)Cu and atomic
      absorption spectroscopy revealed no differences in the copper content of the
      brain, heart, spleen, and kidney. Consistent with these findings, the activity of
      copper-zinc superoxide dismutase in these tissues was equivalent in wild-type and
      ceruloplasmin-deficient mice. Hepatic iron was elevated 3.5-fold in
      aceruloplasminemic mice because of the loss of ferroxidase function. Hepatic
      copper content was markedly increased in aceruloplasminemic mice. As no
      differences were observed in copper absorption or biliary copper excretion, these
      data suggest that in these animals, hepatocyte copper intended for ceruloplasmin
      incorporation is trafficked into a compartment that is less available for biliary
      copper excretion. Taken together, these data reveal no essential role for
      ceruloplasmin in copper metabolism and suggest a previously unappreciated
      complexity to the subcellular distribution of this metal within the hepatocyte
      secretory pathway.

PMID- 11461925
TI  - Fatal propionic acidemia in mice lacking propionyl-CoA carboxylase and its rescue
      by postnatal, liver-specific supplementation via a transgene.
AB  - Propionic acidemia (PA) is an inborn error of metabolism caused by the genetic
      deficiency of propionyl-CoA carboxylase (PCC). By disrupting the alpha-subunit
      gene of PCC, we created a mouse model of PA (PCCA(-/-)), which died in 24-36 h
      after birth due to accelerated ketoacidosis. A postnatal, liver-specific PCC
      expression via a transgene in a far lower level than that in wild-type liver,
      allowed PCCA(-/-) mice to survive the newborn and early infant periods,
      preventing a lethal fit of ketoacidosis (SAP(+)PCCA(-/-) mice). Interestingly,
      SAP(+)PCCA(-/-) mice, in which the transgene expression increased after the late
      infant period, continued to grow normally while mice harboring a persistent low
      level of PCC died in the late infant period due to severe ketoacidosis, clearly
      suggesting the requirement of increased PCC supplementation in proportion to the
      animal growth. Based on these results, we propose a two-step strategy to achieve
      an efficient PA prevention in human patients: a partial PCC supplementation in
      the liver during the newborn and early infant periods, followed by a larger
      amount of supplementation in the late infant period.

PMID- 11461926
TI  - Peptidoglycan recognition proteins: a novel family of four human innate immunity
      pattern recognition molecules.
AB  - The innate immune system recognizes microorganisms through a series of pattern
      recognition receptors that are highly conserved in evolution. Insects have a
      family of 12 peptidoglycan recognition proteins (PGRPs) that recognize
      peptidoglycan, a ubiquitous component of bacterial cell walls. We report cloning
      of three novel human PGRPs (PGRP-L, PGRP-Ialpha, and PGRP-Ibeta) that together
      with the previously cloned PGRP-S, define a new family of human pattern
      recognition molecules. PGRP-L, PGRP-Ialpha, and PGRP-Ibeta have 576, 341, and 373
      amino acids coded by five, seven, and eight exons on chromosomes 19 and 1, and
      they all have two predicted transmembrane domains. All mammalian and insect PGRPs
      have at least three highly conserved C-terminal PGRP domains located either in
      the extracellular or in the cytoplasmic (or in both) portions of the molecules.
      PGRP-L is expressed in liver, PGRP-Ialpha and PGRP-Ibeta in esophagus (and to a
      lesser extent in tonsils and thymus), and PGRP-S in bone marrow (and to a lesser
      extent in neutrophils and fetal liver). All four human PGRPs bind peptidoglycan
      and Gram-positive bacteria. Thus, these PGRPs may play a role in recognition of
      bacteria in these organs.

PMID- 11461927
TI  - Modulation of tumor necrosis factor apoptosis-inducing ligand- induced NF-kappa B
      activation by inhibition of apical caspases.
AB  - Tumor necrosis factor (TNF) apoptosis-inducing ligand (TRAIL), a member of the
      TNF family, induces apoptosis in many transformed cells. We report TRAIL-induced
      NF-kappaB activation, concomitant with production of the pro-inflammatory
      cytokine Interleukin-8 in the relatively TRAIL-insensitive cell line, HEK293. In
      contrast, TRAIL-induced NF-kappaB activation occurred in HeLa cells only upon
      pretreatment with the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe)
      fluoromethyl ketone (z-VAD.fmk), indicating that this was due to a caspase
      sensitive component of TRAIL-induced NF-kappaB activation. NF-kappaB activation
      was mediated by the death receptors, TRAIL-R1 and -R2, but not by TRAIL-R3 or -R4
      and was only observed in HeLa cells in the presence of z-VAD.fmk. Receptor
      interacting protein, an obligatory component of TNF-alpha-induced NF-kappaB
      activation, was cleaved during TRAIL-induced apoptosis. We show that receptor
      interacting protein is recruited to the native TRAIL death-inducing signaling
      complex (DISC) and that recruitment is enhanced in the presence of z-VAD.fmk,
      thus providing an explanation for the potentiation of TRAIL-induced NF-kappaB
      activation by z-VAD.fmk in TRAIL-sensitive cell lines. Examination of the TRAIL
      DISC in sensitive and resistant cells suggests that a high ratio of c-FLIP to
      caspase-8 may partially explain cellular resistance to TRAIL-induced apoptosis.
      Sensitivity to TRAIL-induced apoptosis was also modulated by inhibition or
      activation of NF-kappaB. Thus, in some contexts, modulation of NF-kappaB
      activation possibly at the level of apical caspase activation at the DISC may be
      a key determinant of sensitivity to TRAIL-induced apoptosis.

PMID- 11461928
TI  - Up-regulation of functionally impaired insulin-like growth factor-1 receptor in
      scrapie-infected neuroblastoma cells.
AB  - A growing body of evidence suggests that an altered level or function of the
      neurotrophic insulin-like growth factor-1 receptor (IGF-1R), which supports
      neuronal survival, may underlie neurodegeneration. This study has focused on the
      expression and function of the IGF-1R in scrapie-infected neuroblastoma cell
      lines. Our results show that scrapie infection induces a 4-fold increase in the
      level of IGF-1R in two independently scrapie-infected neuroblastomas, ScN2a and
      ScN1E-115 cells, and that the increased IGF-1R level was accompanied by increased
      IGF-1R mRNA levels. In contrast to the elevated IGF-1R expression in ScN2a,
      receptor binding studies revealed an 80% decrease in specific (125)I-IGF-1
      binding sites compared with N2a cells. This decrease in IGF-1R-binding sites was
      shown to be caused by a 7-fold decrease in IGF-1R affinity. Furthermore, ScN2a
      showed no significant difference in IGF-1 induced proliferative response, despite
      the noticeable elevated IGF-1R expression, putatively explained by the reduced
      IGF-1R binding affinity. Additionally, IGF-1 stimulated IGF-1Rbeta tyrosine
      phosphorylation showed no major change in the dose-response between the cell
      types, possibly due to altered tyrosine kinase signaling in scrapie-infected
      neuroblastoma cells. Altogether these data indicate that scrapie infection
      affects the expression, binding affinity, and signal transduction mediated by the
      IGF-1R in neuroblastoma cells. Altered IGF-1R expression and function may weaken
      the trophic support in scrapie-infected neurons and thereby contribute to
      neurodegeneration in prion diseases.

PMID- 11461929
TI  - Plants synthesize ethanolamine by direct decarboxylation of serine using a
      pyridoxal phosphate enzyme.
AB  - The established pathways from serine to ethanolamine are indirect and involve
      decarboxylation of phosphatidylserine. Here we show that plants can decarboxylate
      serine directly. Using a radioassay based on ethanolamine (Etn) formation,
      pyridoxal 5'-phosphate-dependent l-serine decarboxylase (SDC) activity was
      readily detected in soluble extracts from leaves of diverse species, including
      spinach, Arabidopsis, and rapeseed. A putative Arabidopsis SDC cDNA was
      identified by searching GenBank for sequences homologous to other amino acid
      decarboxylases and shown by expression in Escherichia coli to encode a soluble
      protein with SDC activity. This cDNA was further authenticated by complementing
      the Etn requirement of a yeast psd1 psd2 mutant. In a parallel approach, a cDNA
      was isolated from a rapeseed library by its ability to complement the Etn
      requirement of a yeast cho1 mutant and shown by expression in E. coli to specify
      SDC. The deduced Arabidopsis and rapeseed SDC polypeptides are 90% identical,
      lack obvious targeting signals, and belong to amino acid decarboxylase group II.
      Recombinant Arabidopsis SDC was shown to exist as a tetramer and to contain
      pyridoxal 5'-phosphate. It does not attack d-serine, l-phosphoserine, other l
      amino acids, or phosphatidylserine and is not inhibited by Etn, choline, or their
      phosphoesters. As a soluble, pyridoxal 5'-phosphate enzyme, SDC contrasts sharply
      with phosphatidylserine decarboxylases, which are membrane proteins that have a
      pyruvoyl cofactor.

PMID- 11461930
TI  - The glomerular epithelial cell anti-adhesin podocalyxin associates with the actin
      cytoskeleton through interactions with ezrin.
AB  - During development, renal glomerular epithelial cells (podocytes) undergo
      extensive morphologic changes necessary for creation of the glomerular filtration
      apparatus. These changes include formation of interdigitating foot processes,
      replacement of tight junctions with slit diaphragms, and the concomitant opening
      of intercellular urinary spaces. It was postulated previously and confirmed
      recently that podocalyxin, a sialomucin, plays a major role in maintaining the
      urinary space open by virtue of the physicochemical properties of its highly
      negatively charged ectodomain. This study examined whether the highly conserved
      cytoplasmic tail of podocalyxin also contributes to the unique organization of
      podocytes by interacting with the cytoskeletal network found in their cell bodies
      and foot processes. By immunocytochemistry, it was shown that podocalyxin and the
      actin binding protein ezrin are co-expressed in podocytes and co-localize along
      the apical plasma membrane, where they form a co-immunoprecipitable complex.
      Selective detergent extraction followed by differential centrifugation revealed
      that some of the podocalyxin cosediments with actin filaments. Moreover, its
      sedimentation is dependent on polymerized actin and is mediated by complex
      formation with ezrin. Once formed, podocalyxin/ezrin complexes are very stable,
      because they are insensitive to actin depolymerization or inactivation of Rho
      kinase, which is known to be necessary for regulation of ezrin and to mediate Rho
      dependent actin organization. These data indicate that in podocytes, podocalyxin
      is complexed with ezrin, which mediates its link to the actin cytoskeleton. Thus,
      in addition to its ectodomain, the cytoplasmic tail of podocalyxin also likely
      contributes to maintaining the unique podocyte morphology.

PMID- 11461931
TI  - Feedback control of glomerular vascular tone in neuronal nitric oxide synthase
      knockout mice.
AB  - For further elucidation of the role of neuronal nitric oxide synthase (nNOS) in
      macula densa (MD) cells, experiments were performed in anesthetized nNOS knockout
      mice (nNOS -/-). At comparable levels of arterial BP, renal blood flow was not
      significantly different between nNOS +/+ and nNOS -/- (1.7 +/- 0.2 versus 1.4 +/-
      0.1 ml/min), and autoregulation of renal blood flow was maintained to a pressure
      level of approximately 85 mmHg in both groups of mice (n = 6 in each group). The
      fall in proximal tubular stop-flow pressure in response to an increase in loop of
      Henle perfusion rate from 0 to 30 nl/min was comparable in nNOS +/+ and -/- mice
      (40.7 +/- 1.6 to 32 +/- 2 mmHg versus 40.6 +/- 1.6 to 31.6 +/- 2 mmHg; not
      significant; n = 13 versus 18 nephrons). Luminal application of the nonselective
      NOS inhibitor nitro-L-arginine (10(-3) and 10(-2) M) enhanced the perfusion
      dependent fall in stop-flow pressure in nNOS +/+ (7 +/- 1 to 13 +/- 2 mmHg; P <
      0.05) but not in nNOS -/- (7 +/- 1 to 8 +/- 1 mmHg; not significant) mice. nNOS 
      /- mice exhibited a lower nephron filtration rate, compared with nNOS +/+, during
      free-flow collections from early distal tubules (influence of MD intact, 7 +/-
      0.7 versus 10.9 +/- 1 nl/min; P = 0.002) but not from late proximal tubule
      (influence of MD minimized, 10.1 +/- 1 versus 11.7 +/- 1 nl/min; not significant;
      n = 16 nephrons). Distal Cl concentration and fractional absorption of fluid or
      chloride up to the early distal tubule was not different between nNOS -/- and +/+
      mice. The data indicate that nNOS in MD tonically attenuates the GFR-lowering
      influence of ambient luminal NaCl, which may serve to increase the fluid and
      electrolyte load to the distal tubule, consistent with a role of MD nNOS in
      tubuloglomerular feedback resetting.

PMID- 11461932
TI  - Effects of ammonia on acid-base transport by the B-type intercalated cell.
AB  - Ammonia, in addition to its role as a constituent of urinary net acid excretion,
      stimulates cortical collecting duct (CCD) net bicarbonate reabsorption. The
      current study sought to begin determining the cellular transport processes
      through which ammonia regulates bicarbonate reabsorption by testing whether
      ammonia stimulates B-type intercalated cell bicarbonate secretion, bicarbonate
      reabsorption, or both. The effects of ammonia on single CCD intercalated cells
      was studied by use of measurements of intracellular pH taken from in vitro
      microperfused CCD segments after luminal loading of the pH-sensitive fluorescent
      dye BCECF. These results showed, first, that ammonia inhibited B-cell
      unidirectional bicarbonate secretion and that this occurred despite no effect of
      ammonia on apical Cl(-)/HCO(3)(-) exchange activity. Second, ammonia increased
      the contribution of a SCH28080-sensitive apical H(+)-K(+)-ATPase to basal
      intracellular pH regulation and it stimulated basolateral Cl(-)/HCO(3)(-)
      exchange activity. Thus, ammonia activated both apical proton secretion and
      basolateral base exit, consistent with stimulation of unidirectional bicarbonate
      reabsorption. It was concluded that ammonia regulates CCD net bicarbonate
      reabsorption, at least in part, through the coordinated regulation of the
      separate processes of B-cell bicarbonate reabsorption and bicarbonate secretion.
      These effects do not reflect a general activation of ion transport but, instead,
      reflect coordinated and specific regulation of ion transport.

PMID- 11461933
TI  - Human kidney tubules detoxify chloroacetaldehyde, a presumed nephrotoxic
      metabolite of ifosfamide.
AB  - The nephrotoxic effects of the antineoplastic drug ifosfamide have been
      attributed to its hepatic metabolite chloroacetaldehyde. The effects of
      chloroacetaldehyde on isolated human kidney cortex tubules metabolizing lactate
      (a physiologic substrate in human kidneys) were investigated. At concentrations
      of > or =0.5 mM, chloroacetaldehyde was toxic to the human kidney tubules, as
      demonstrated by a dramatic decrease in cellular ATP levels and a large increase
      in lactate dehydrogenase release; chloroacetaldehyde also stimulated pyruvate
      accumulation and inhibited lactate removal and glucose synthesis. These effects,
      which were associated with incomplete disappearance of chloroacetaldehyde and
      extensive depletion of the cellular CoA, acetyl-CoA, and glutathione contents,
      were prevented by the addition of thiol-protecting drugs (mesna and amifostine).
      Human kidney tubules were demonstrated to metabolize chloroacetaldehyde at high
      rates, presumably via aldehyde dehydrogenase, which is very active in human
      kidneys. Carbon-13 nuclear magnetic resonance spectroscopy measurements indicated
      that human kidney tubules converted [2-(13)C]chloroacetaldehyde to [2
      (13)C]chloroacetate, the further metabolism of which was very limited. At
      equimolar concentrations, chloroacetate was much less toxic than
      chloroacetaldehyde, indicating that chloroacetate synthesis from
      chloroacetaldehyde by human kidney tubules represents a detoxification mechanism
      that could play a role in vivo in preventing or limiting the nephrotoxic effects
      observed during ifosfamide therapy.

PMID- 11461934
TI  - Impaired function of endothelial pressure-activated cation channel in salt
      sensitive genetic hypertension.
AB  - Mechanosensitive ion channels have been suggested to act as endothelial
      mechanosensors for hemodynamic forces. The present study tested the hypothesis
      that the pressure-activated cation channel (PAC), a novel type of endothelial
      mechanosensitive ion channel, is involved in salt sensitivity in the Sabra rat
      model of hypertension. Groups of Sabra salt-sensitive (SBH/y) and salt-resistant
      (SBN/y) rats were loaded with deoxycorticosterone-acetate (DOCA)-salt for 8 wk or
      were fed a regular diet. Single channel function of PAC in SBH/y and SBN/y rats
      was investigated in intact endothelium of mesenteric artery using the patch-clamp
      technique. After DOCA-salt treatment, the SBH/y rats showed a full hypertensive
      response, whereas SBN/y rats were normotensive. Rats of both strains that
      received a regular diet were normotensive. In endothelium of both Sabra rats,
      Ca(2+) permeable PAC that was activated by positive pipette pressures was
      identified. Apparent PAC density (percentage of patches with PAC activity) was
      reduced in hypertensive SBH/y rats that were loaded with DOCA-salt compared with
      salt-loaded normotensive SBN/y rats (6 +/- 2% versus 24 +/- 8%, respectively; P <
      0.05). In normotensive SBH/y and SBN/y rats that received a regular diet, PAC
      density was not altered. Mechanosensitivity and unitary conductance of
      endothelial PAC were similar in both strains under a regular diet as well as salt
      loading with DOCA-salt. In conclusion, the decreased density of PAC in mesenteric
      endothelium from hypertensive SBH/y rats indicates an impaired ion channel
      regulation. The defective PAC function presumably leads to an impaired
      mechanosensitive Ca(2+) entry and might contribute to endothelial dysfunction and
      high BP in this type of salt-sensitive genetic hypertension.

PMID- 11461935
TI  - Nitric oxide synthesis and oxidative stress in the renal cortex of rats with
      diabetes mellitus.
AB  - Experiments were performed to test the hypothesis that diabetes mellitus disrupts
      the balance between synthesis and degradation of nitric oxide (NO) in the renal
      cortex. Diabetes was induced by injection of streptozotocin, and sufficient
      insulin was provided to maintain moderate hyperglycemia for the ensuing 2 wk.
      Despite an 80% increase in total NO synthase activity measured by L-citrulline
      assay, nicotinamide adenine dinucleotide phosphate-diaphorase staining was
      unaltered, and no changes in NO synthase isoform protein levels or their
      distribution were evident in renal cortex from diabetic rats. Superoxide anion
      production was accelerated twofold in renal cortical slices from diabetic rats,
      with an associated 50% increase in superoxide dismutase activity. Western blots
      prepared by use of a monoclonal antinitrotyrosine antibody revealed an
      approximately 70-kD protein in renal cortex from sham rats, the nitrotyrosine
      content of which was threefold greater in cortical samples from diabetic rats.
      These observations indicate that the early stage of diabetes mellitus provokes
      accelerated renal cortical superoxide anion production in a setting of normal or
      increased NO production. This situation can be expected to promote peroxynitrite
      formation, resulting in the tyrosine nitration of a single protein of unknown
      identity, as well as a decline in the bioavailability of NO. These events are
      consistent with the postulate that oxidative stress promotes NO degradation in
      the renal cortex during the early stage of diabetes mellitus.

PMID- 11461936
TI  - Evidence for basolateral P2Y(6) receptors along the rat proximal tubule:
      functional and molecular characterization.
AB  - In this study, the distribution of P2Y(6) receptor mRNA in rat nephron segments
      was investigated and a functional approach was used to analyze basolateral
      protein expression. Reverse transcription-PCR studies revealed more intense
      expression of P2Y(6) receptor mRNA in the proximal tubule and the thick ascending
      limb of Henle's loop, less intense expression in the thin descending limb and the
      cortical and outer medullary collecting ducts, and no detectable expression in
      either the thin ascending limb or the inner medullary collecting duct. Dose
      dependent calcium responses to basolateral administration of UDP (a selective
      agonist for the P2Y(6) receptor) were observed in the proximal tubule but not in
      any of the other segments studied. In the proximal tubule, intracellular calcium
      concentration changes induced by UDP were associated with increased production of
      inositol phosphates, as were those induced by ATP and norepinephrine. However,
      UDP-induced intracellular calcium concentration changes were different,
      exhibiting no plateau after the initial peak; moreover, a single stimulation with
      a high concentration of UDP induced full desensitization of the UDP-sensitive
      calcium pathway but did not alter the responsiveness of the proximal tubule to
      ADP (a specific P2Y(1) receptor agonist), ATP or norepinephrine. In summary, this
      report demonstrates that P2Y(6) receptor mRNA is expressed in most segments of
      the rat nephron but that basolateral expression of the protein is restricted to
      the proximal tubule, where the receptor is coexpressed with the P2Y(1) receptor.
      The differences in the distributions of P2Y(6) receptor mRNA and UDP responses
      may indicate the presence of luminal receptors in other nephron segments.

PMID- 11461937
TI  - Transcriptional and post-transcriptional alterations of IkappaBalpha in active
      minimal-change nephrotic syndrome.
AB  - Minimal-change nephrotic syndrome (MCNS) is a renal disease characterized by
      heavy glomerular proteinuria and increased production of cytokines by immune
      cells. Because of the central role of nuclear factor-kappaB (NF-kappaB) in the
      regulation of cytokine expression, its activity during the relapse and remission
      phases of steroid-sensitive MCNS was analyzed. During relapse, nuclear extracts
      from peripheral blood mononuclear cells displayed high levels of NF-kappaB DNA
      binding activity, consisting primarily of p50/RelA (p65) complexes. NF-kappaB p65
      and IkappaBalpha proteins were barely detected or not detected in cytosolic
      fractions during relapse, in contrast to remission. The lack of expression of
      IkappaBalpha protein was associated with downregulation of IkappaBalpha mRNA and
      increases in the levels of the mRNA encoding the proteasome alpha2 subunit
      proteolytic pathway. In addition, inhibition of proteasome activity induced
      cytosolic accumulation of phosphorylated IkappaBalpha and significant reductions
      in the NF-kappaB binding activity in nuclear extracts from peripheral blood
      mononuclear cells from patients experiencing relapses. These results suggest that
      alterations in the NF-kappaB/IkappaBalpha regulatory feedback loop may contribute
      to the immunologic abnormalities that occur in steroidsensitive MCNS.

PMID- 11461938
TI  - Cyclopentenone prostaglandins inhibit cytokine-induced nf-kappab activation and
      chemokine production by human mesangial cells.
AB  - In the kidney an uncontrolled inflammatory response to an acute insult may lead
      to chronic inflammation, permanent tissue damage, and progressive renal
      insufficiency. Resolution of acute inflammation likely is dependent on endogenous
      regulatory mechanisms activated in parallel with mediators of renal inflammation.
      These mechanisms are postulated to attenuate the renal expression of
      proinflammatory cytokines, including the chemokines responsible for recruiting
      leukocytes to the kidney, thus facilitating the transition from inflammation to
      healing. To understand the regulation of the inflammatory response within the
      kidney, the effects of anti-inflammatory J series cyclopentenone prostaglandins
      on chemokine production by human mesangial cells were examined. Treatment of
      mesangial cells with prostaglandin J(2) and 15-deoxy-Delta(12,14)-prostaglandin
      J(2) blocked interleukin-1beta-induced monocyte chemoattractant protein-1 mRNA
      expression and protein production. This correlated with failure of the
      transcription factor nuclear factor-kappaB (NF-kappaB) to translocate to the
      nucleus and bind to its recognition motif, a step required for cytokine-induced
      monocyte chemoattractant protein-1 gene activation. NF-kappaB failed to
      translocate because the cyclopentenone prostaglandins attenuated degradation of
      the NF-kappaB inhibitor IkappaB-alpha. These data suggest that certain
      prostaglandins can limit the extent of renal chemokine expression and thus may
      have an important role in resolving renal inflammation.

PMID- 11461939
TI  - Role of mast cell tryptase in renal interstitial fibrosis.
AB  - Renal interstitial fibrosis is characterized by increased proliferation of
      fibroblasts and excessive accumulation of extracellular matrix. Mast cell
      tryptase has been implicated in the development of tissue fibrosis in skin and
      lungs. However, the significance of mast cell tryptase in human renal diseases
      has not been investigated. The potential role of mast cell-derived tryptase in
      the development of renal fibrosis was studied using immunohistochemical
      techniques and cultured human renal fibroblast cell lines. Semiquantitative
      immunostaining analysis of samples from 70 patients with several renal diseases,
      including IgA glomerulonephritis (GN) (n = 30), non-IgA GN (n = 5), membranous GN
      (n = 5), focal segmental glomerulosclerosis (n = 4), minor glomerular
      abnormalities (n = 5), lupus nephritis (n = 3), and acute or chronic
      tubulointerstitial nephritis (n = 18), revealed that the degree of renal
      interstitial fibrosis was well correlated with the number of infiltrating
      tryptase-positive mast cells (P < 0.01). Mast cells could not be detected in
      damaged glomeruli in any form of renal disease. [(3)H]Thymidine uptake
      experiments demonstrated that DNA synthesis by cultured renal fibroblasts was
      increased with the concentration of tryptase (0.5 to 5 nM) coincubated with
      heparin and was suppressed by coincubation with the protease inhibitors leupeptin
      and benzamidine hydrochloride. Tryptase alone also increased DNA synthesis by
      fibroblasts but exhibited less effectiveness, compared with the combination of
      tryptase and heparin. Conversely, heparin alone suppressed DNA synthesis by
      fibroblasts. Metabolic [(35)S]methionine-labeling experiments with cultured renal
      fibroblasts indicated that tryptase increased the synthesis of fibronectin and
      collagen type I, in a dose-dependent manner. These findings suggest that mast
      cell tryptase plays a role in the proliferation and extracellular matrix protein
      production of renal interstitial fibroblasts and thus contributes to the
      development of renal interstitial fibrosis.

PMID- 11461940
TI  - Human immunodeficiency virus-1 induces loss of contact inhibition in podocytes.
AB  - Human immunodeficiency virus-associated nephropathy (HIVAN) affects up to 10% of
      HIV-positive black adults and children and is the leading cause of renal disease
      in infected individuals. The disease is characterized by proliferation of renal
      epithelial cells, both glomerular and tubular. Diseased kidneys are enlarged, and
      glomerular visceral epithelial cells (podocytes) express proliferation markers.
      In a transgenic murine model of HIVAN expressing a deletion construct of HIV-1,
      the identical pathologic features are observed. It was demonstrated that HIV-1
      mRNA is expressed in renal epithelium of the transgenic mouse and in patients
      with HIVAN, suggesting a direct role for HIV-1 in disease pathogenesis in both
      humans and the murine model. For investigating the mechanisms responsible for
      proliferative changes in podocytes, the HIV-1 transgenic mouse was bred onto the
      immortomouse background, and conditionally immortalized transgenic and
      nontransgenic podocyte cell lines were established. Transgenic podocytes
      demonstrated increased spontaneous proliferation, compared with nontransgenic
      podocytes at confluence, and they were found to have a greater percentage of
      cells in the proliferative phase of the cell cycle. It is striking that
      transgenic podocytes were not contact inhibited and formed aggregates in soft
      agar. Aggregates also formed when nontransgenic podocytes were infected with the
      identical HIV-1 construct used to generate the transgenic model. This
      demonstrates that the loss of contact inhibition is due to a direct effect of HIV
      1. Therefore, proliferation induced by HIV-1 gene expression is likely to play a
      key role in the pathogenesis of HIVAN.

PMID- 11461941
TI  - Involvement of the activin-follistatin system in tubular regeneration after renal
      ischemia in rats.
AB  - This study was conducted to investigate the involvement of the activin
      follistatin system in renal regeneration after ischemic injury. Expression of
      mRNA for the activin beta(A) subunit was not detected in normal kidneys but
      increased markedly after renal ischemia. Immunoreactive beta(A) subunit was
      detected in tubular cells of the outer medulla in ischemic but not normal
      kidneys. Expression of mRNA for follistatin, an antagonist of activin A, was
      abundant in tubular cells of the outer medulla in normal kidneys and decreased
      significantly after renal ischemia. For assessment of the role of the activin
      follistatin system in renal regeneration after ischemic injury, recombinant
      follistatin was intravenously infused into rats with renal ischemia, at the time
      of reperfusion. Exogenous follistatin prevented the histologic changes induced by
      ischemic injury, reduced apoptosis in tubular cells, and accelerated tubular cell
      proliferation. Serum levels of creatinine and blood urea nitrogen were
      significantly lower in follistatin-treated rats. Conversely, intravenous
      administration of recombinant activin A inhibited tubular cell proliferation
      after ischemic injury. These results indicate that the activin-follistatin system
      participates in renal regeneration after ischemic injury. Follistatin
      administered intravenously accelerates renal regeneration after renal ischemia,
      presumably by blocking the actions of endogenous activin.

PMID- 11461942
TI  - Pharmacologic modulators of nitric oxide exacerbate tubulointerstitial
      inflammation in proteinuric rats.
AB  - Nitric oxide (NO) regulates inflammatory responses partly by cell-specific
      inhibition of the transcription factor nuclear factor kappaB (NF-kappaB). This
      study investigated the effect of continuous oral administration of an NO donor
      (molsidomine [Mol]), NO precursor (L-arginine [L-arg]), or selective inhibitors
      of inducible NO synthase (iNOS; aminoguanidine [AG], L-N(6)-(1-iminoethyl)lysine
      [L-NIL]) on the progression of tubulointerstitial inflammation and NF-kappaB
      activation in a non-immune model of chronic glomerular disease (Adriamycin
      nephropathy [AN]), from day 8 until day 30 after disease induction. On day 30,
      rats with AN had heavy proteinuria, reduced creatinine clearance, and
      tubulointerstitial disease. Treatment with both AG and L-NIL exacerbated the
      progression of AN as evidenced by (1) increased renal cortical malondialdehyde;
      (2) reduced creatinine clearance; and (3) increased tubular atrophy, interstitial
      volume, and monocyte infiltration. Unexpectedly, Mol also increased renal
      malondialdehyde and worsened tubular injury, whereas L-arg had no effect. The
      increase in renal cortical NF-kappaB activation in AN was not altered by AG, L
      NIL, or Mol, but the mRNA expression of monocyte chemoattractant protein-1,
      interleukin-10, and osteopontin were elevated in these groups. Nitrite release
      from kidney slices reduced in AN. Treatment with Mol restored renal nitrite
      release to normal, whereas neither L-arg nor the NOS inhibitors had an effect. It
      is concluded that endogenous iNOS-derived NO has a protective role against
      tubulointerstitial injury and cytokine production in AN. However, the pro-oxidant
      activity of NO donors may limit their potential benefit in proteinuric renal
      disease.

PMID- 11461943
TI  - Angiotensin II and prostaglandin interactions on systemic and renal effects of L
      NAME in humans.
AB  - For investigation of whether interactions between prostaglandins and angiotensin
      II modulate renal response to acute nitric oxide synthesis inhibition in humans,
      seven young volunteers who were kept on a 240-mM Na diet underwent four
      experiments with 90 min of infusion of 3.0 microg/kg.min(-1) NG-nitro-L-arginine
      methyl ester (L-NAME), each preceded by a 3-d treatment with placebo (PL), 50 mg
      of losartan (LOS), 75 to 125 mg of indomethacin (IND), or both drugs. Mean
      arterial pressure (MAP), GFR, effective renal plasma flow (ERPF), and Na
      excretion rate (UNaV) were measured at baseline and from 0 to 45 min and 45 to 90
      min of L-NAME infusion. After PL, L-NAME reduced GFR by 5% at 45 min (P < 0.05)
      and by 9% at 90 min (P < 0.001), ERPF by 11 to 17% (P < 0.001), and UNaV by 28 to
      45% (P < 0.001). MAP, unchanged at 45 min, rose by 5% (P < 0.001) at 90 min. LOS
      prevented pressor but not renal effects of L-NAME. With L-NAME+IND, MAP rose even
      at 45 min (+5%; P < 0.001 versus baseline) with a 10% rise at 90 min (P < 0.001).
      Changes in GFR (-13 to -20%), ERPF (-19 to -26%), and UNaV (-51 to -70%) were
      greater than those with L-NAME+PL or L-NAME+LOS (P < 0.05 to 0.001). With L
      NAME+IND+LOS, MAP did not increase, and GFR, ERPF, and UNaV fell much less than
      with L-NAME+IND alone (P < 0.02 to 0.001) with no differences versus PL or LOS
      alone. Angiotensin II blockade does not affect renal changes caused by L-NAME but
      prevents their potentiation by prostaglandin inhibition. Thus, endogenous
      prostaglandins counteract renal actions of endogenous angiotensin II in Na
      repleted humans even when nitric oxide synthesis is inhibited.

PMID- 11461944
TI  - Opportunities for improving the care of patients with chronic renal
      insufficiency: current practice patterns.
AB  - There are between 2 and 13 million Americans with chronic kidney disease (CKD).
      Recent reports suggest that their treatment is currently suboptimal. To further
      investigate this issue, patterns of practice for the treatment of patients with
      CKD who were enrolled in a large health maintenance organization in New Mexico
      were analyzed. Among the >200,000 patients who were enrolled in the health
      maintenance organization between 1994 and 1997, a cohort of 1658 patients who
      exhibited at least two gender-specific, elevated creatinine concentrations (Cr),
      separated by at least 90 d, were identified. The proportions of patients with Cr
      values of <2.0, 2.0 to 2.9, 3.0 to 3.9, and > or =4.0 mg/dl were 73, 17, 3, and
      7%, respectively. The majority of patients were treated by a primary care
      physician until Cr values reached 3.0 mg/dl, at which time a nephrologist was
      consulted. Care tended to be transferred to the nephrologist when the Cr reached
      4.0 mg/dl. Only 7.4% of patients received erythropoietin (EPO). Use of EPO
      increased as Cr increased. EPO was unlikely to be prescribed unless the patient
      had visited a nephrologist. Fewer than one half of all patients with CKD and
      fewer than 20% of patients with CKD with Cr values of > or =4.0 mg/dl received an
      angiotensin-converting enzyme inhibitor (ACEI). Nephrologists were not more
      likely to prescribe ACEI than were primary care physicians. Diabetic patients
      were more likely to receive ACEI than were nondiabetic patients, but ACEI use was
      quite low even among diabetic patients with CKD. The average number of
      hospitalizations per patient-year increased as Cr increased and was more than
      twice as high for patients with Cr values of > or =4.0 mg/dl, compared with those
      with Cr values of <2.0 mg/dl. The reasons for hospitalization were more likely to
      be related to comorbidities than to CKD itself, however. There are many
      opportunities to improve the care of patients with CKD. Better adherence to
      practices known to be of clinical benefit for patients with CKD not only will
      improve patient outcomes but also may reduce the costs of care. Providers, policy
      makers, and payers should view CKD as a major public health problem and initiate
      innovative programs to address this growing patient population.

PMID- 11461945
TI  - High adenosine and deoxyadenosine concentrations in mononuclear cells of
      hemodialyzed patients.
AB  - Infections are one of the most important complications of hemodialysis (HD). The
      high concentrations of adenosine (Ado) and of its metabolites during HD may
      contribute to the dialysis-induced immune deficiency through their known ability
      to alter lymphocyte function. The influence of HD on Ado metabolism was assessed
      in mononuclear cells through the measurement of (1) the concentrations of
      nucleosides in mononuclear cells and (2) the activities of mononuclear cell Ado
      deaminase (MCADA) and Ado kinase, two enzymes involved in Ado concentration
      regulation. Nine end-stage renal failure hemodialyzed patients (five men and four
      women; mean age, 69 +/- 10 yr) and eight healthy volunteers (four men and four
      women; mean age, 53 +/- 19 yr) were included in the study. Before HD, Ado,
      deoxyadenosine, and inosine concentrations were respectively 2.9-, 2.5-, and 2.5
      fold higher in mononuclear cells of patients than in healthy volunteers. During
      HD, Ado concentration decreased by 34%, whereas inosine concentration increased
      by 27%. Before HD, MCADA activity level was 2.1-fold lower in patients than in
      control subjects. After HD, MCADA activity increased by nearly 50% but remained
      lower than in control subjects. Ado kinase activity level of patients did not
      differ from that of control subjects and was unchanged by HD. The influence of
      Ado on in vitro mononuclear cell proliferation and interferon-gamma production
      also was evaluated. Ado inhibited cell proliferation and interferon-gamma
      production in a dose-dependent manner, and these inhibitions were stronger for
      patients than for healthy volunteers. The high concentrations of Ado and
      deoxyadenosine in mononuclear cells and the low MCADA activity level likely are
      involved in the immune defect of patients who are undergoing HD.

PMID- 11461946
TI  - Screening for subclinical stenosis in native vessel arteriovenous fistulae.
AB  - Guidelines recommend the use of ultrasound dilution techniques (UDT), including
      measurement of access recirculation (AR) and access blood flow (Q(a)), to screen
      for subclinical vascular access dysfunction. Although these techniques are
      efficacious in polytetrafluoroethylene grafts, data in native vessel
      arteriovenous fistulae (AVF) are lacking. A prospective observational study was
      conducted to evaluate the utility of UDT screening in AVF. Q(a) and AR were
      measured bimonthly. Positive studies required fistulograms and were defined by
      Q(a) < 500 ml/min, DeltaQ(a) > 20% from baseline or AR > 5%. Accesses with
      stenosis underwent percutaneous angioplasty. After 1 yr, there were 1355 mo of
      follow-up in 177 patients. There were 44 positive studies in 40 patients. Q(a)
      was <500 ml/min in 36 (82%), DeltaQ(a) was >20% in 5 (11%), and AR was >5% in 6
      (14%). Of patients with Q(a) < 500 ml/min, 29 (81%) had stenosis. Only two
      patients (40%) with DeltaQ(a) > 20% but Q(a) > 500 ml/min had stenosis. No
      patient with AR > 5% had stenosis unless Q(a) was also <500 ml/min. Immediate
      patency rate was 93% post-PTA. Mean Q(a) increased from 303 +/- 154 ml/min to 602
      +/- 220 ml/min (P < 0.0001), and mean urea reduction ratio increased from 70.4 +/
      8.4% to 74.6 +/- 6.5% (P = 0.003) post-PTA. The results demonstrate that UDT
      could detect subclinical stenoses in AVF, and most lesions were amenable to
      angioplasty. AVF that underwent PTA delivered higher Q(a) and urea reduction
      ratio, and immediate patency rates were acceptable. Access failure after negative
      UDT was unusual. Measuring AR increases the time required to perform UDT but does
      not improve utility. Serial measurements of Q(a) alone may be the best strategy
      for screening AVF.

PMID- 11461947
TI  - Vascular endothelial growth factor is essential for hyperglycemia-induced
      structural and functional alterations of the peritoneal membrane.
AB  - Long-term peritoneal dialysis is associated with the development of functional
      and structural alterations of the peritoneal membrane. Long-term exposure to the
      high glucose concentrations in conventional peritoneal dialysate has been
      implicated in the pathogenesis of peritoneal hyperpermeability and
      neoangiogenesis. Vascular endothelial growth factor (VEGF) is an endothelial
      specific growth factor that potently stimulates microvascular permeability and
      proliferation. High glucose exposure upregulates VEGF expression in various cell
      types and tissues. This study investigated whether VEGF plays a pathogenetic role
      in hyperglycemia-induced microvascular dysfunction in the peritoneal membrane.
      The peritoneal microcirculation of streptozotocin-induced diabetic rats and age
      matched controls was studied in vivo with a combination of functional and
      morphologic techniques. The diabetic microcirculation was characterized by an
      elevated transport of small solutes, indicating the presence of an increased
      effective vascular surface area. The leakage of FITC-albumin was more rapid in
      diabetic vessels, suggesting hyperpermeability for macromolecules. Structurally,
      an increased vascular density with focal areas of irregular capillary budding was
      found in the diabetic peritoneum. The hyperglycemia-induced structural and
      functional microvascular alterations were prevented by long-term treatment with
      neutralizing anti-VEGF monoclonal antibodies, whereas treatment with isotype
      matched control antibodies had no effect. VEGF blockade did not influence
      microvascular density or macromolecular leakage in control rats, demonstrating
      specificity for the hyperglycemia-induced alterations. The present results thus
      support an causative link among high glucose exposure, upregulation of VEGF, and
      peritoneal microvascular dysfunction.

PMID- 11461948
TI  - Recipient age and weight affect chronic renal allograft rejection in rats.
AB  - Nephron doses and immune responses change with age. Therefore, age is a potential
      risk factor for graft survival after kidney transplantation. The aim of this
      study was to determine whether age-related differences are of importance for long
      term outcomes after renal transplantation. Kidneys from Fisher 344 rats were
      orthotopically transplanted into nephrectomized Lewis rats. Kidneys were
      transplanted using donors and recipients of three age levels, i.e., young (8 wk
      of age), adult (16 wk of age), and old (40 wk of age). Rats were killed 24 wk
      after transplantation, and functional, morphologic, and molecular evaluations
      were performed. Recipient age, rather than donor age, determined graft survival
      rates. No significant correlation was observed between donor kidney weight on the
      day of transplantation and morphologic results. Advanced recipient age was
      associated with reduced creatinine clearance, more severe histologic injuries,
      including extended glomerular sclerosis, interstitial fibrosis, and vascular
      lesions, more pronounced cellular infiltration, and greater expression of
      transforming growth factor-beta and platelet-derived growth factor A and B
      chains. Although no significant correlation between donor age or kidney weight on
      the day of transplantation and morphologic results was observed, there was a
      significant correlation between recipient body weight on the day of
      transplantation and allograft injury. It is concluded that recipient age and
      weight affect chronic renal rejection. Renal allografts may benefit from young
      recipient age but may deteriorate in old recipients, suggesting effects of
      recipient functional demand on long-term outcomes.

PMID- 11461949
TI  - A controlled trial comparing two doses of cyclosporine in conjunction with
      mycophenolate mofetil and corticosteroids.
AB  - It is unknown whether the addition of mycophenolate mofetil (MMF) to cyclosporine
      (CsA) and prednisone after renal transplantation (RTx) allows for a reduced dose
      of CsA, to minimize the incidence of CsA-related side effects and to reduce
      costs. Therefore, 313 renal allograft recipients were randomized for treatment
      with MMF (1000 mg twice a day), prednisone, and either conventional- or low-dose
      CsA during the first 3 mo after RTx. The target trough levels were 300 and 150
      ng/ml, respectively, during the first 3 mo and 150 ng/ml in both groups
      thereafter. A total of 313 patients were included: 161 patients received a
      conventional dose and 152 received a low dose of CsA. During the first 6 mo after
      RTx, graft failure or patient death occurred in 19 of 161 patients (12%) in the
      conventional-dose group and in 11 of 152 patients (7%) in the low-dose group (not
      significant). Biopsy-proven acute rejection occurred in 36 of 161 patients (22%)
      in the conventional-dose group and in 29 of 152 patients (19%) in the low-dose
      group (not significant). The incidence of delayed graft function was similar in
      both groups (31 of 161 [19%] versus 28 of 152 [18%]; not significant). Serum
      creatinine did not differ between the conventional- and the low-dose groups: 151
      +/- 56 micromol/L versus 142 +/- 49 micromol/L at 3 mo and 141 +/- 60 micromol/L
      versus 136 +/- 49 micromol/L at 6 mo. There were no differences between the
      groups regarding BP, lipid metabolism, and infectious complications. In the low
      dose group, an estimated $500 per patient was saved on the costs of CsA. In
      conclusion, the addition of MMF to CsA and prednisone after RTx allows the use of
      a lower-than-conventional dose of CsA, without increasing the risk of rejection.

PMID- 11461950
TI  - Mycophenolate mofetil does not modify the incidence of cytomegalovirus (CMV)
      disease after kidney transplantation but prevents CMV-induced chronic graft
      dysfunction.
AB  - Ganciclovir, which is used to treat cytomegalovirus (CMV) infection, has been
      shown in rodent models to abolish CMV-mediated chronic cellular damage and
      endothelial cell proliferation; when associated with mycophenolate mofetil (MMF),
      it has been shown to increase its anti-herpes virus activity. This study tested
      the hypothesis that kidney graft recipients who received antirejection
      prophylaxis with MMF and who were treated with ganciclovir for a declared CMV
      disease could be protected from chronic graft dysfunction. Investigated was the
      impact of ganciclovir-treated CMV diseases in consecutive first kidney recipients
      according to their immunosuppressive therapy. The azathioprine (Aza)-treated
      group (Aza group) included 319 patients. The MMF-treated group (MMF group)
      included 126 patients. CMV disease was clinically defined and confirmed by
      virological proof of CMV infection and was treated for at least 14 d with
      ganciclovir. Despite having the same incidence (21.6% in the Aza group versus
      24.6% in the MMF group) and severity, CMV disease was significantly associated
      with graft loss independent of acute rejection episodes or other factors when
      tested in a Cox proportional model in the Aza group only (P < 10(-4)). It was
      shown for the first time that patients whose CMV disease is treated with
      ganciclovir while they are on MMF therapy are protected from the long-term
      deleterious consequences of CMV disease on graft survival, independent of acute
      rejection. It is suggested that the enhanced anti-herpes virus activity of
      ganciclovir by MMF could contribute to this reported effect, which may represent
      a significant contribution of MMF efficacy to graft survival.

PMID- 11461951
TI  - Rats injected with syngenic rat apoptotic neutrophils develop antineutrophil
      cytoplasmic antibodies.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) are present in sera from patients
      with various forms of vasculitis-associated glomerulonephritis. Because
      autoantibodies may be directed against antigens presented by apoptotic cells,
      generation of ANCA using apoptotic neutrophils (PMN) in syngenic Brown Norway
      (BN) rats was attempted. These rats are T-helper type 2-prone animals, already
      used successfully in other ANCA-positive animal models. BN rats received repeated
      injections of buffer or of nonapoptotic or apoptotic PMN aged in cultures, in the
      footpad and once intravenously. Four of five rats that received injections of PMN
      aged for 48 h developed ANCA, which cross-reacted with human leukocyte elastase
      in three cases. None of the rats that received injections of freshly isolated
      neutrophils developed ANCA. One rat that received buffer injection and that
      exhibited chronic skin infection developed delayed ANCA. None of the rats showed
      signs of disease: no weight loss and no proteinuria. Then a subnephritogenic dose
      of antibody directed against rat glomerular basement membrane was injected. Rats
      then were killed, and different organs were frozen and studied. No significant
      lesions were found in kidneys or lungs. It is concluded that injections of
      apoptotic but not freshly isolated PMN can generate ANCA in BN rats. Additional
      studies are needed to elucidate the immunization mechanism and the ability of
      these autoantibodies to initiate vasculitis in these experimental animals.

PMID- 11461952
TI  - PAX2 gene mutation in a family with isolated renal hypoplasia.
AB  - The PAX2 gene encodes a transcription factor that plays a critical role in the
      development of the urogenital tract, eyes, ears, and central nervous system.
      Recently, renal hypoplasia was observed to be part of the renal-coloboma
      syndrome, which is caused by heterozygous mutations of the PAX2 gene. The renal
      coloboma syndrome is a rare autosomal dominant syndrome that involves optic nerve
      colobomas and renal anomalies. For investigation of whether PAX2 mutations occur
      in patients with isolated renal hypoplasia, patient DNA was analyzed for PAX2
      mutations, by using PCR and direct sequencing. The study involved 20 patients
      with bilateral renal hypoplasia associated with decreased renal function.
      Heterozygous PAX2 mutations were detected in two patients, i.e., a novel nonsense
      mutation (C to A transversion at position 1566 in exon 9) in patient 1 and
      another novel nonsense mutation (C to T transversion at position 1318 in exon 7)
      in patient 2. The nucleotide changes for patients 1 and 2 directly introduced
      stop codons, presumably resulting in a message for a truncated PAX2 protein that
      lacked a partial transactivation domain. An ophthalmologic examination revealed a
      very mild, asymptomatic coloboma in patient 2, whereas the fundus was normal for
      patient 1. The mutation cosegregated with the presence of renal hypoplasia in the
      family of patient 1, appearing de novo in the mother of the patient, which
      strongly suggests that this mutation was the cause of renal hypoplasia in this
      family. This study demonstrates for the first time that PAX2 mutations can be
      responsible for isolated renal hypoplasia.

PMID- 11461953
TI  - Stem cells: a journey into a new frontier.

PMID- 11461954
TI  - Atheroembolic renal disease.

PMID- 11461955
TI  - Milestones in nephrology: Presence of luminal K+, a prerequisite for active NaCl
      transport in the cortical thick ascending limb of Henle's loop of rabbit kidney.
AB  - Originally published in Pflugers Arch. 392:92-94, 1981. Reprinted with author
      commentary by Dr. Schlatter.

PMID- 11461956
TI  - Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on
      oxidative stress and cell death induced by hydrogen peroxide, 4-hydroxynonenal or
      serum deprivation: potentiation of injury by ALS-related mutant superoxide
      dismutases and protection by Bcl-2.
AB  - Mutations in Cu/Zn-superoxide dismutase (SOD1) are associated with some cases of
      familial amyotrophic lateral sclerosis (ALS). We overexpressed Bcl-2, wild-type
      SOD1 or mutant SOD1s (G37R and G85R) in NT-2 and SK-N-MC cells. Overexpression of
      Bcl-2 rendered cells more resistant to apoptosis induced by serum withdrawal,
      H2O2 or 4-hydroxy-2-trans-nonenal (HNE). Overexpression of Bcl-2 had little
      effect on levels of protein carbonyls, lipid peroxidation, 8-hydroxyguanine (8
      OHG) or 3-nitrotyrosine. Serum withdrawal or H2O2 raised levels of protein
      carbonyls, lipid peroxidation, 8-OHG and 3-nitrotyrosine, changes that were
      attenuated in cells overexpressing Bcl-2. Overexpression of either SOD1 mutant
      tended to increase levels of lipid peroxidation, protein carbonyls, and 3
      nitrotyrosine and accelerated viability loss induced by serum withdrawal, H2O2 or
      HNE, accompanied by greater rises in oxidative damage parameters. The effects of
      mutant SOD1s were attenuated by Bcl-2. By contrast, expression of wild-type SOD1
      rendered cells more resistant to loss of viability induced by serum deprivation,
      HNE or H2O2. The levels of lipid peroxidation in wild-type SOD1 transfectants
      were elevated. Overexpression of mutant SOD1s makes cells more predisposed to
      undergo apoptosis in response to several insults. Our cellular systems appear to
      mimic events in patients with ALS or transgenic mice overexpressing mutant SOD1.

PMID- 11461957
TI  - Intrathecally delivered glial cell line-derived neurotrophic factor produces
      electrically evoked release of somatostatin in the dorsal horn of the spinal
      cord.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor with an
      established role in sensory neuron development. More recently it has also been
      shown to support adult sensory neuron survival and exert a neuroprotective effect
      on damaged sensory neurons. Some adult small-sized dorsal root ganglion (DRG)
      cells that are GDNF-sensitive sensory neurons express the inhibitory peptide
      somatostatin (SOM). Thus, we tested the hypothesis that prolonged GDNF
      administration would regulate SOM expression in sensory neuron cell bodies in the
      dorsal root ganglia (DRG) and activity-induced release of SOM from axon terminals
      in the dorsal horn. Continuous intrathecal delivery of GDNF for 11-13 days
      significantly increased the number of small DRG cells that expressed SOM.
      Furthermore, GDNF treatment evoked SOM release in the isolated dorsal horn
      following electrical stimulation of the dorsal roots that was otherwise
      undetectable in control rats. Conversely capsaicin-induced release of SOM (EC(50)
      50 nM) was not modified by GDNF treatment. These results show that GDNF can
      regulate central synaptic function in SOM-containing sensory neurons.

PMID- 11461958
TI  - 1,2-bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid induces caspase-mediated
      apoptosis and reactive oxygen species-mediated necrosis in cultured cortical
      neurons.
AB  - Sustained alteration in [Ca(2+)]i triggers neuronal death. We examined
      morphological and signaling events of Ca(2+)-deficiency-induced neuronal death.
      Cortical cell cultures exposed to 20 microM 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator,
      underwent neuronal apoptosis within 12 h that was evident by shriveled cell
      bodies, aggregated and condensed nuclear chromatin, and disrupted nuclear
      membrane. Thereafter, surviving neurons revealed typical necrosis, accompanied by
      swelling of cell body and mitochondria, over 24 h. Both apoptosis and necrosis
      were prevented by inclusion of 1 microg/mL cycloheximide, a protein synthesis
      inhibitor. Treatment with BAPTA-AM induced translocation of Bax into mitochondria
      within 4 h and release of cytochrome c from mitochondria over 4-12 h. An active
      fragment of caspase-3, a downstream mediator of cytochrome c, was observed within
      8 h and cleaved PHF-1-positive tau. Administration of zVAD-fmk, a broad inhibitor
      of caspases, or DEVD-amc, a selective inhibitor of caspase-3, selectively
      prevented the apoptosis component of BAPTA-AM neurotoxicity. In contrast, BAPTA
      AM-induced necrosis was propagated through sequential production of superoxide,
      mitochondrial and cytoplasmic reactive oxygen species. Combined treatment with
      caspase inhibitors and antioxidants blocked BAPTA-AM neurotoxicity. The present
      study suggests that neurons deficient in [Ca(2+)]i undergo caspase-3-mediated
      apoptosis and reactive oxygen species (ROS)-mediated necrosis.

PMID- 11461959
TI  - Serotonin depletion produces long lasting increase in striatal glutamatergic
      transmission.
AB  - The ability of serotonin (5-HT) to influence striatal glutamatergic transmission
      was examined by determining changes over time in glutamate extracellular levels,
      transporter expression and synaptosomal uptake in rats with lesion of
      serotonergic neurones. By 8 days after intraraphe injections of 5,7
      dihydroxytryptamine, producing 80% decreases in striatal tissue 5-HT levels, no
      changes were observed in the glutamatergic transmission. When 5-HT depletion was
      almost complete (21 days post-lesion), high affinity glutamate uptake in striatal
      synaptosomal preparations was significantly increased (156% of control), although
      no changes in striatal GLT1, GLAST and EAAC1 mRNAs, and GLT1 protein were
      detected by in situ hybridization and immunohistochemistry. Meanwhile, the
      serotonin lesion produced large increases in basal extracellular levels of
      glutamate and glutamine (364% and 259%, respectively) determined in awake rats by
      in vivo microdialysis, whereas no change was observed in dopamine levels as
      compared with control rats. High potassium depolarization as well as L-trans
      pyrrolidine-2,4-dicarboxylate, also induced larger increases in extracellular
      levels of glutamate in lesioned rats than in controls. Finally, similar changes
      in glutamate transmission were observed by 3 months post-lesion. These results
      suggest that 5-HT has a long lasting and tonic inhibitory influence on the
      striatal glutamatergic input, without affecting the basal dopaminergic
      transmission.

PMID- 11461960
TI  - Homocysteine potentiates beta-amyloid neurotoxicity: role of oxidative stress.
AB  - The cause of neuronal degeneration in Alzheimer's disease (AD) has not been
      completely clarified, but has been variously attributed to increases in cytosolic
      calcium and increased generation of reactive oxygen species (ROS). The beta
      amyloid fragment (Abeta) of the amyloid precursor protein induces calcium influx,
      ROS and apoptosis. Homocysteine (HC), a neurotoxic amino acid that accumulates in
      neurological disorders including AD, also induces calcium influx and oxidative
      stress, which has been shown to enhance neuronal excitotoxicity, leading to
      apoptosis. We examined the possibility that HC may augment Abeta neurotoxicity.
      HC potentiated the Abeta-induced increase in cytosolic calcium and apoptosis in
      differentiated SH-SY-5Y human neuroblastoma cells. The antioxidant vitamin E and
      the glutathione precursor N-acetyl-L-cysteine blocked apoptosis following
      cotreatment with HC and Abeta, indicating that apoptosis is associated with
      oxidative stress. These findings underscore that moderate accumulation of
      excitotoxins at concentrations that alone do not appear to initiate adverse
      events may enhance the effects of other factors known to cause neurodegeneration
      such as Abeta.

PMID- 11461961
TI  - Nuclear factor kappaB is a critical determinant in N-methyl-D-aspartate receptor
      mediated neuroprotection.
AB  - The role of a nuclear factor kappaB (NF-kappaB) in NMDA receptor-mediated
      neuroprotection is not known. A candidate sequence from the 5' flanking region of
      exon 3 of the rat brain-derived neurotrophic factor (BDNF) gene was used to show
      that exposure of rat cerebellar granule cells to 100 microM NMDA activated a
      specific DNA binding activity that was blocked by the NMDA receptor antagonist MK
      801. Anti-p65 antibody or anti-p50 antibody 'supershifted' the DNA binding
      activity, suggesting that the DNA-protein complex was composed of p65 and p50
      subunits. NMDA receptor-mediated neuroprotection was blocked when cerebellar
      neurons were transfected with a double-stranded oligonucleotide containing the
      BDNF gene NF-kappaB sequence. Furthermore, nuclear extracts prepared from neurons
      treated with NMDA and the double-stranded NF-kappaB oligonucleotide showed
      reduced DNA binding activity to the target sequence, supporting the idea that NF
      kappaB may be involved in the transcriptional activation of the BDNF gene. To
      address this issue, we quantified the level of exon 3-specific BDNF mRNA.
      Relative to GAPDH mRNA levels and compared with untreated neurons, NMDA increased
      exon 3-specific BDNF mRNA twofold. In contrast, pretreatment of neurons with the
      NF-kappaB target DNA abolished the increase in BDNF mRNA following addition of
      NMDA. We also determined that BDNF itself induced an NF-kappaB DNA binding
      activity. Taken together, these data support a mechanism where NF-kappaB plays a
      critical role in NMDA-mediated neuroprotection.

PMID- 11461962
TI  - Oxidative stress mediates neuronal DNA damage and apoptosis in response to
      cytosine arabinoside.
AB  - Cytosine arabinoside (AraC) is a nucleoside analog that produces significant
      neurotoxicity in cancer patients. The mechanism by which AraC causes neuronal
      death is a matter of some debate because the conventional understanding of AraC
      toxicity requires incorporation into newly synthesized DNA. Here we demonstrate
      that AraC-induced apoptosis of cultured cerebral cortical neurons is mediated by
      oxidative stress. AraC-induced cell death was reduced by treatment with several
      different free-radical scavengers (N-acetyl-L-cysteine, dipyridamole, uric acid,
      and vitamin E) and was increased following depletion of cellular glutathione
      stores. AraC induced the formation of reactive oxygen species in neurons as
      measured by an increase in the fluorescence of the dye 5-(6)-carboxy-2',7'
      dichlorodihydrofluorescein diacetate. AraC produced DNA single-strand breaks as
      measured by single-cell gel electrophoresis and the level of DNA strand breakage
      was reduced by treatment with the free radical scavengers. These data support a
      model in which AraC induces neuronal apoptosis by provoking the generation of
      reactive oxygen species, causing oxidative DNA damage and initiating the p53
      dependent apoptotic program. These observations suggest the use of antioxidant
      therapies to reduce neurotoxicity in AraC chemotherapeutic regimens.

PMID- 11461963
TI  - Dibutyryl-cAMP (dbcAMP) up-regulates astrocytic chloride-dependent L
      [3H]glutamate transport and expression of both system xc(-) subunits.
AB  - Recent studies have shown that N(6),2'-O-dibutyryladenosine 3':5' cyclic
      monophosphate (dbcAMP) increases the expression of specific subtypes of Na(+)
      dependent glutamate transporters in cultured astrocytes. Our group also found
      that treatment of astrocytes with dbcAMP for several days increases the Na(+)
      independent accumulation of L-[3H]glutamate. In this study, the properties of
      this Na(+)-independent accumulation were characterized, and the mechanism by
      which dbcAMP up-regulates this process was investigated. This accumulation was
      markedly reduced in the absence of Cl(-) and was also inhibited by several anion
      exchange inhibitors, including 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid, 4,4'-dinitrostilbene-2,2'-disulfonic acid and 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid, suggesting that this activity is
      mediated by a Cl(-)-dependent transporter. In addition, this activity was
      inhibited by micromolar concentrations of several inhibitors of another Cl(-)
      dependent (Na(+)-independent) transport activity frequently referred to as system
      xc(-) (L-cystine, L-alpha-aminoadipate, L-homocysteate, quisqualate, beta-N
      oxalyl-l-alpha,beta-diaminopropionate, ibotenate). This activity was
      competitively inhibited by several phenylglycine derivatives previously
      characterized as inhibitors of metabotropic glutamate receptor activation. The
      concentration-dependence for Na(+)-independent, Cl(-)-dependent L-[3H]glutamate
      uptake activity was compared for dbcAMP-treated and untreated astrocytes.
      Treatment with dbcAMP increased the V(max) of this Cl(-)-dependent transport
      activity by sixfold but had no effect on the K(m) value. System xc(-) requires
      two subunits, xCT and 4F2hc/CD98, to reconstitute functional activity. We found
      that dbcAMP caused a twofold increase in the levels of xCT mRNA and a sevenfold
      increase in the levels of 4F2hc/CD98 protein. This study indicates that dbcAMP up
      regulates Cl(-)-dependent L-[3H]glutamate transport activity in astrocytes and
      suggests that this effect is related to increased expression of both subunits of
      system xc(-). Because this activity is thought to be important for the synthesis
      of glutathione and protection from oxidant injury, understanding the regulation
      of system xc(-) may provide alternate approaches to limit this form of injury.

PMID- 11461964
TI  - The transcription factor E2F1 promotes dopamine-evoked neuronal apoptosis by a
      mechanism independent of transcriptional activation.
AB  - The E2F1 transcription factor plays an important role in promoting neuronal
      apoptosis; however, it is not clear how E2F1 does this. Here we show that E2F1 is
      involved in dopamine (DA)-evoked apoptosis in cerebellar granule neurons (CGNs).
      E2F1 -/- CGNs and CGNs expressing an antisense E2F1 cDNA were significantly
      protected from DA-toxicity relative to controls. The neuronal protection was
      accompanied by significantly reduced caspase 3 activity. E2F1-mediated neuronal
      apoptosis did not require activation of gene transcription because: (1) ectopic
      expression of E2F1 or its mutants lacking the transactivation domain induced
      neuronal apoptosis, whereas an E2F1 mutant lacking the DNA-binding domain did
      not; (2) under all of these conditions, known E2F1 target genes including cyclin
      A, cdc2 and p19(ARF) were not induced; and (3) DA-evoked neuronal apoptosis was
      associated with up-regulated E2F1, but not transcription of its target genes.
      Finally, E2F1-mediated neuronal apoptosis was associated with reduced nuclear
      factor (NF)-kappaB DNA-binding activity. Taken together, these data suggest that
      E2F1 promotes DA-evoked caspase 3-dependent neuronal apoptosis by a mechanism
      independent of gene transactivation, and this may possibly occur through
      inhibition of anti-apoptotic genes including NF-kappaB.

PMID- 11461965
TI  - JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in
      nerve growth factor-deprived sympathetic neurons.
AB  - The stress activated protein kinase pathway culminates in c-Jun phosphorylation
      mediated by the Jun Kinases (JNKs). The role of the JNK pathway in sympathetic
      neuronal death is unclear in that apoptosis is not inhibited by a dominant
      negative protein of one JNK kinase, SEK1, but is inhibited by CEP-1347, a
      compound known to inhibit this overall pathway but not JNKs per se. To evaluate
      directly the apoptotic role of the JNK isoform that is selectively expressed in
      neurons, JNK3, we isolated sympathetic neurons from JNK3-deficient mice and
      quantified nerve growth factor (NGF) deprivation-induced neuronal death,
      oxidative stress, c-Jun phosphorylation, and c-jun induction. Here, we report
      that oxidative stress in neurons from JNK3-deficient mice is normal after NGF
      deprivation. In contrast, NGF-deprivation-induced increases in the levels of
      phosphorylated c-Jun, c-jun, and apoptosis are each inhibited in JNK3-deficient
      mice. Overall, these results indicate that JNK3 plays a critical role in
      activation of c-Jun and apoptosis in a classic model of cell-autonomous
      programmed neuron death.

PMID- 11461966
TI  - A significant increase in both basal and maximal calcineurin activity in the rat
      pilocarpine model of status epilepticus.
AB  - This study focused on the effects of status epilepticus on the activity of
      calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is
      an important modulator of many neuronal processes, including learning and memory,
      induction of apoptosis, receptor function and neuronal excitability. Therefore, a
      status epilepticus-induced alteration of the activity of this important
      phosphatase would have significant physiological implications. Status epilepticus
      was induced by pilocarpine injection and allowed to continue for 60 min. Brain
      region homogenates were then assayed for calcineurin activity by
      dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus
      dependent increase in both basal and Mn(2+)-dependent calcineurin activity was
      observed in homogenates isolated from the cortex and hippocampus, but not the
      cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to
      50 microM okadaic acid. The increase in basal activity was also resistant to 100
      microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate
      affinity were increased following status epilepticus. However, the increase in
      calcineurin activity was not found to be due to an increase in calcineurin enzyme
      levels. Finally, increase in calcineurin activity was found to be NMDA-receptor
      activation dependent. The data demonstrate that status epilepticus resulted in a
      significant increase in both basal and maximal calcineurin activity.

PMID- 11461967
TI  - Attenuation of neurotoxicity in cortical cultures and hippocampal slices from
      E2F1 knockout mice.
AB  - The E2F1 transcription factor modulates neuronal apoptosis induced by
      staurosporine, DNA damage and beta-amyloid. We demonstrate E2F1 involvement in
      neuronal death induced by the more physiological oxygen-glucose deprivation (OGD)
      in mouse cortical cultures and by anoxia in mouse hippocampal slices. E2F1(+/+)
      and (-/-) cultures were comparable, in that they contained similar neuronal
      densities, responded with similar increases in intracellular calcium
      concentration ([Ca(2+)]i) to glutamate receptor agonists, and showed similar NMDA
      receptor subunit mRNA expression levels for NR1, NR2A and NR2B. Despite these
      similarities, E2F1(-/-) cultures were significantly less susceptible to neuronal
      death than E2F1(+/+) cultures 24 and 48 h following 120-180 min of OGD.
      Furthermore, the absence of E2F1 significantly improved the ability of CA1
      neurons in hippocampal slices to recover synaptic transmission following a
      transient anoxic insult in vitro. These results, along with our finding that E2F1
      mRNA levels are significantly increased following OGD, support a role for E2F1 in
      the modulation of OGD- and anoxia-induced neuronal death. These findings are
      consistent with studies showing that overexpression of E2F1 in postmitotic
      neurons causes neuronal degeneration and the absence of E2F1 decreases infarct
      volume following cerebral ischemia.

PMID- 11461968
TI  - The olfactory G protein G(alphaolf) possesses a lower GDP-affinity and
      deactivates more rapidly than G(salphashort): consequences for receptor-coupling
      and adenylyl cyclase activation.
AB  - The olfactory G protein G(alphaolf) differs from the short splice variant of
      G(salpha) (G(salphaS)) in 80 amino acids, but little is known about biochemical
      differences between G(alphaolf) and G(salphaS). We addressed this question by
      analyzing fusion proteins of the beta2-adrenoceptor (beta2AR) and G(alphaolf) and
      G(salphaS), respectively, using Sf9 insect cells as expression system. The fusion
      ensured defined receptor/G protein stoichiometry and efficient coupling. High
      affinity agonist binding studies showed that G(alphaolf) possesses a lower GDP
      affinity than G(salphaS) As a result, the agonist-free beta2AR and the beta2AR
      occupied by partial agonists were more efficient at promoting GDP-dissociation
      from G(alphaolf) than from G(salphaS) a assessed by guanosine 5'-O-(3
      thiotriphosphate) binding, adenylyl cyclase (AC) activity and GTP hydrolysis.
      Basal AC activity in the absence of GTP was almost sixfold lower in membranes
      expressing beta2AR-G(alphaolf) than in membranes expressing beta2AR-G(salphaS) at
      similar levels, reflecting the lower abundance of G(alphaolf-GDP) relative to
      G(salphaS-GDP). The maximum agonist-stimulated AC activity with beta2AR
      G(salphaS) was more than twofold higher than with beta2AR-G(alphaolf), but the
      relative agonist-stimulation of AC with beta2AR-G(alphaolf) was much greater than
      with beta2AR-G(salphaS). The difference in maximum AC activity can be explained
      by more rapid deactivation of G(alphaolf-GTP) by GTP hydrolysis and GTP
      dissociation relative to G(salphaS-GTP). Taken together, there are biochemical
      differences between G(alphaolf) and G(salphaS), supporting different roles of
      these G proteins in vivo.

PMID- 11461969
TI  - Anandamide degradation and N-acylethanolamines level in wild-type and CB1
      cannabinoid receptor knockout mice of different ages.
AB  - CD1 mice lacking the CB1 receptors (knockout, KO) were compared with wild-type
      littermates for their ability to degrade N-arachidonoylethanolamine (anandamide,
      AEA) through a membrane transporter (AMT) and a fatty acid amide hydrolase
      (FAAH). The regional distribution and age-dependence of AMT and FAAH activity
      were investigated. Anandamide membrane transporter and FAAH increased with age in
      knockout mice, whereas they showed minor changes in wild-type animals.
      Remarkably, they were higher in all brain areas of 6-month-old knockout versus
      wild-type mice, and even higher in 12-month-old animals. The molecular mass
      (approximately 67 kDa) and isoelectric point (approximately 7.6) of mouse brain
      FAAH were determined and the FAAH protein content was shown to parallel the
      enzyme activity. The kinetic constants of AMT and FAAH in the cortex of wild-type
      and knockout mice at different ages suggested that different amounts of the same
      proteins were expressed. The cortex and hippocampus of wild-type and knockout
      mice contained the following N-acylethanolamines: AEA (8% of total), 2
      arachidonoylglycerol (5%), N-oleoylethanolamine (20%), N-palmitoylethanolamine
      (53%) and N-stearoylethanolamine (14%). These compounds were twice as abundant in
      the hippocampus as in the cortex. Minor differences were observed in AEA or 2
      arachidonoylglycerol content in knockout versus wild-type mice, whereas the other
      compounds were lower in the hippocampus of knockout versus wild-type animals.

PMID- 11461970
TI  - Inhibitory effect of somatostatin on neutral amino acid transport in isolated
      brain microvessels.
AB  - In the presence of somatostatin-14 or some of its receptorial agonists, the
      uptake of large neutral amino acids by isolated brain microvessels was found to
      be inhibited up to 50%, no other transport system being affected. Although the
      luminal and abluminal sides of brain endothelial cells are both capable of taking
      up large neutral amino acids, only uptake from the abluminal side appears to be
      inhibited by somatostatin. The involvement of a type-2 somatostatin receptor was
      suggested by assays with a series of receptor-specific somatostatin agonists, and
      was confirmed by the release of inhibition caused by a specific type-2 receptor
      antagonist. A type-2-specific mRNA was indeed shown to be present in both bovine
      brain microvessels ex vivo and primary cultures of endothelial cells from rat
      brain microvessels.

PMID- 11461971
TI  - Serotonin activation of the ERK pathway in Hermissenda: contribution of calcium
      dependent protein kinase C.
AB  - The mitogen-activated protein kinase (MAPK) cascade is an important contributor
      to synaptic plasticity and learning in both vertebrates and invertebrates. In the
      nudibranch mollusk Hermissenda, phosphorylation and activation of the
      extracellular signal-regulated protein kinase (ERK), a key member of a MAPK
      cascade, is produced by one-trial and multitrial Pavlovian conditioning. Several
      signal transduction pathways that are activated by 5-hydroxytryptamine (5-HT) and
      may contribute to conditioning have been identified in type B photoreceptors.
      However, the regulation of ERK activity by 'upstream' signaling molecules has not
      been previously investigated in Hermissenda. In the present study we examined the
      role of protein kinase C (PKC) in the serotonin (5-HT) activation of the ERK
      pathway. The phorbol ester TPA produced an increase in ERK phosphorylation that
      was blocked by the PKC inhibitors GF109203X or Go6976. TPA-dependent ERK
      phosphorylation was also blocked by the MEK1 inhibitors PD098059 or U0126. The
      increased phosphorylation of ERK by 5-HT was reduced but not blocked by
      pretreatment with the calcium chelator BAPTA-AM or pretreatment with Go6976 or
      GF109203X. These results indicate that Ca(2+)-dependent PKC activation
      contributes to ERK phosphorylation, although a PKC-independent pathway is also
      involved in 5-HT-dependent ERK phosphorylation and activation.

PMID- 11461972
TI  - Glutamate induces focal adhesion kinase tyrosine phosphorylation and actin
      rearrangement in heterologous mGluR1-expressing CHO cells via calcium/calmodulin
      signaling.
AB  - Group 1 metabotropic glutamate receptors (mGluR1 and mGluR5) stimulate
      phospholipase C (PLC) and lead to mobilization of intracellular Ca(2+) and
      activation of protein kinase C (PKC). In this investigation, using heterologous
      receptor-expressing Chinese hamster ovary (CHO) cells, we showed that stimulation
      of mGluR1 or mGluR5 with glutamate rapidly increases tyrosine phosphorylation of
      focal adhesion kinase (FAK) (maximum at 1-3 min) in a dose-dependent manner (half
      maximal responses at approximately 2 microM). In mGluR1-expressing cells, the
      glutamate-induced increase of FAK tyrosine phosphorylation was blocked by not
      only the PLC inhibitor, U73122, but also depletion of intracellular Ca(2+) and
      effectively abrogated by calmodulin (CaM) inhibitors, calmidazolium and
      fluphenazine. However, neither the PKC inhibitor, GF109203X, nor the CaM kinase
      II inhibitor, KN-62, inhibited glutamate-stimulated FAK tyrosine phosphorylation.
      Stimulation of mGluR1 caused a marked increase in actin stress fiber formation.
      Importantly, this actin rearrangement was prevented by the CaM inhibitor, but not
      by the PKC inhibitor and is thus in a good agreement with the signaling cascade
      of the mGluR1-FAK pathway. These results suggest that the Ca(2+)/CaM signaling
      and its downstream FAK tyrosine phosphorylation play an important role in
      cellular function of mGluR1.

PMID- 11461973
TI  - Apoptotic signaling in dopamine-induced cell death: the role of oxidative stress,
      p38 mitogen-activated protein kinase, cytochrome c and caspases.
AB  - Oxidative stress generated by dopamine (DA) oxidation could be one of the factors
      underlying the selective vulnerability of nigral dopaminergic neurons in
      Parkinson's diseases. Here we show that DA induces apoptosis in SH-SY5Y
      neuroblastoma cells demonstrated by activation of caspase-9 and caspase-3,
      cleavage of poly(ADP-ribose) polymerase as well as nuclear condensation. We also
      show that p38 mitogen-activated protein kinase is activated within 10 min of DA
      treatment, which precedes the onset of apoptosis because the potent p38 kinase
      inhibitor SB203580 protects against DA-induced cell death as well as against
      caspase-9 and caspase-3 activation. In addition, the antioxidant N-acetyl-L
      cysteine (NAC) effectively blocks DA-induced p38 kinase activation, caspase-9 and
      caspase-3 cleavage and subsequent apoptosis, indicating that DA triggers
      apoptosis via a signaling pathway that is initiated by the generation of reactive
      oxygen species (ROS). Dopamine exerts its toxicity principally intracellularly as
      the DA uptake inhibitor, nomifensine significantly reduces DA-induced cell death
      as well as activation of p38 kinase and caspase-3. Furthermore, DA induces
      mitochondrial cytochrome c release, which is dependent on p38 kinase activation
      and precedes the cleavage of caspases. These observations indicate that DA
      induces apoptosis primarily by generating ROS, p38 kinase activation, cytochrome
      c release followed by caspase-9 and caspase-3 activation.

PMID- 11461974
TI  - Identification of the region of non-Abeta component (NAC) of Alzheimer's disease
      amyloid responsible for its aggregation and toxicity.
AB  - The non-beta-amyloid (Abeta) component of Alzheimer's disease amyloid (NAC) and
      its precursor alpha-synuclein have been linked to amyloidogenesis in several
      neurodegenerative diseases. NAC and alpha-synuclein both form beta-sheet
      structures upon ageing, aggregate to form fibrils, and are neurotoxic. We
      recently established that a peptide comprising residues 3-18 of NAC retains these
      properties. To pinpoint the exact region responsible we have carried out assays
      of toxicity and physicochemical properties on smaller fragments of NAC. Toxicity
      was measured by the ability of fresh and aged peptides to inhibit the reduction
      of the redox dye 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide
      (MTT) by rat pheochromocytoma PC12 cells and human neuroblastoma SHSY-5Y cells.
      On immediate dissolution, or after ageing, the fragments NAC(8-18) and NAC(8-16)
      are toxic, whereas NAC(12-18), NAC(9-16) and NAC(8-15) are not. Circular
      dichroism indicates that none of the peptides displays beta-sheet structure;
      rather all remain random coil throughout 24 h. However, in acetonitrile, an
      organic solvent known to induce beta sheet, fragments NAC(8-18) and NAC(8-16)
      both form beta-sheet structure. Only NAC(8-18) aggregates, as indicated by
      concentration of peptide remaining in solution after 3 days, and forms fibrils,
      as determined by electron microscopy. These findings indicate that residues 8-16
      of NAC, equivalent to residues 68-76 in alpha-synuclein, comprise the region
      crucial for toxicity.

PMID- 11461975
TI  - Chronic ethanol exposure delays the 'developmental switch' of the NMDA receptor
      2A and 2B subunits in cultured cerebellar granule neurons.
AB  - Chronic ethanol treatment of cultured neurons from various brain areas has been
      found to increase NMDA receptor function and to alter the levels of some NMDA
      receptor subunit proteins. Because the cultured neurons are exposed to ethanol
      during a period when the NMDA receptor is undergoing developmental changes in
      subunit expression, we wished to determine whether ethanol treatment alters this
      developmental pattern. We found that 3 days of treatment of cerebellar granule
      neurons with ethanol, which was previously reported to increase NMDA receptor
      function, resulted in a delay in the 'developmental switch' of the NR2A and NR2B
      subunits, i.e. the developmental decrease in NR2B and increase in NR2A protein
      expression. As a result, the level of NR2B was higher, and that of NR2A was
      lower, in the ethanol-treated cells than in control cells. Cross-linking
      experiments showed that the changes in total receptor subunit proteins levels
      were reflected in cell-surface expressed proteins, indicating changes in the
      amount of functional receptors. These results were confirmed by a higher potency
      of glycine at the NMDA receptor in the ethanol-treated cells, as determined by
      NMDA/glycine-induced increases in intracellular Ca(2+). The results suggest that
      the mechanism by which ethanol alters NMDA receptor expression in cultured
      neurons, where receptors are undergoing development, differs from the mechanism
      of ethanol's effect on NMDA receptors in adult brain. Changes in the proportion
      of NR2A and NR2B subunits may contribute to effects of ethanol on neuronal
      development.

PMID- 11461976
TI  - Role of alpha2-macroglobulin in regulating amyloid beta-protein neurotoxicity:
      protective or detrimental factor?
AB  - alpha2-Macroglobulin (alpha2M) has been identified as a carrier protein for beta
      amyloid (Abeta) decreasing fibril formation and affecting the neurotoxicity of
      this peptide. The alpha2-macroglobulin receptor/low density lipoprotein receptor
      related protein (LRP) is involved in the internalization and degradation of the
      alpha2M/Abeta complexes and its impairment has been reported to occur in
      Alzheimer's disease. Previous studies have shown alpha2M to determine an
      enhancement or a reduction of Abeta toxicity in different culture systems. In
      order to clarify the role of alpha2M in Abeta neurotoxicity, we challenged human
      neuroblastoma cell lines with activated alpha2M in combination with Abeta. Our
      results show that in neuroblastoma cells expressing high levels of LRP, the
      administration of activated alpha2M protects the cells from Abeta neurotoxicity.
      Conversely, when this receptor is not present alpha2M determines an increase in
      Abeta toxicity as evaluated by MTT and TUNEL assays. In LRP-negative cells
      transfected with the full-length human LRP, the addition of activated alpha2M
      resulted to be protective against Abeta-induced neurotoxicity. By means of
      recombinant proteins we ascribed the neurotoxic activity of alpha2M to its FP3
      fragment which has been previously shown to bind and neutralize transforming
      growth factor-beta. These studies provide evidence for both a neuroprotective and
      neurotoxic role of alpha2M regulated by the expression of its receptor LRP.

PMID- 11461977
TI  - The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2
      nonenal in the Alzheimer's disease brain: the role of Abeta1-42.
AB  - Glutamate transporters are involved in the maintenance of synaptic glutamate
      concentrations. Because of its potential neurotoxicity, clearance of glutamate
      from the synaptic cleft may be critical for neuronal survival. Inhibition of
      glutamate uptake from the synapse has been implicated in several
      neurodegenerative disorders. In particular, glutamate uptake is inhibited in
      Alzheimer's disease (AD); however, the mechanism of decreased transporter
      activity is unknown. Oxidative damage in brain is implicated in models of
      neurodegeneration, as well as in AD. Glutamate transporters are inhibited by
      oxidative damage from reactive oxygen species and lipid peroxidation products
      such as 4-hydroxy-2-nonenal (HNE). Therefore, we have investigated a possible
      connection between the oxidative damage and the decreased glutamate uptake known
      to occur in AD brain. Western blots of immunoprecipitated HNE-immunoreactive
      proteins from the inferior parietal lobule of AD and control brains suggest that
      HNE is conjugated to GLT-1 to a greater extent in the AD brain. A similar
      analysis of beta amyloid (Abeta)-treated synaptosomes shows for the first time
      that Abeta1-42 also increases HNE conjugation to the glutamate transporter.
      Together, our data provide a possible link between the oxidative damage and
      neurodegeneration in AD, and supports the role of excitotoxicity in the
      pathogenesis of this disorder. Furthermore, our data suggests that Abeta may be a
      possible causative agent in this cascade.

PMID- 11461978
TI  - Transition from the paediatric clinic to the adult service.

PMID- 11461979
TI  - Involving patients and the public--is it worth the effort?

PMID- 11461980
TI  - Aldosterone as a determinant of cardiovascular and renal dysfunction.

PMID- 11461981
TI  - Cardiovascular manifestations of HIV infection.

PMID- 11461982
TI  - A clinician's guide to digital X-ray systems.

PMID- 11461983
TI  - Ocular air-gun injury: 19 cases.
AB  - There have been many calls for preventive action against injuries caused by air
      guns. Eye injuries are particularly serious, and we conducted a retrospective
      study to review their characteristics. Ophthalmic consultants in the south-west
      region of England and South Wales were asked to recollect any injuries that had
      resulted from air weapons. Information was recorded on the nature and
      circumstances of the injury, subsequent management, and long-term effects. 19
      cases of ocular injury were identified, sustained at mean age 19.7 years, all in
      the past decade. 15 of the victims were male. At least 12 shootings were
      accidental but 2 were deliberate. The injury was self-inflicted in 5 cases, and
      in 6 the assailant was known to the victim. 9 sustained ruptured globes and 8 had
      severe contusions. Ultimately 4 individuals required enucleation and 2
      evisceration. At last review, visual acuity was no perception of light in 10
      (53%) and "counting fingers" or worse in 16. Victims spent an average of nearly
      10 days as an inpatient. The characteristics of the incidents that lead to ocular
      air-weapon injuries are unchanged. Reform of the firearms laws is probably the
      best way to prevention.

PMID- 11461984
TI  - Sore throat and hyperferritinaemia.

PMID- 11461985
TI  - Jet-ski injury: severe blunt neck trauma with survival.

PMID- 11461986
TI  - An epitrochlear tumour.

PMID- 11461987
TI  - Endocrine evaluation for muscle pain.

PMID- 11461988
TI  - A knife in the back: anaesthetic management.

PMID- 11461989
TI  - Amputations at the London Hospital 1852-1857.
AB  - Between 1852 and 1857 at the London Hospital, 142 amputations were performed in
      136 patients. The most common indication was an injury sustained at work. Overall
      mortality was 46% and the death rate was especially high for lower-limb
      amputations. Most deaths were due to postoperative sepsis. Those who received
      chloroform anaesthesia did worse than those who received ether.

PMID- 11461990
TI  - The key to the sanatoria.

PMID- 11461991
TI  - 65 years of mobile life for all?

PMID- 11461992
TI  - Carbon monoxide poisoning and the eye.

PMID- 11461993
TI  - Changing relationship between the public and the medical profession.

PMID- 11461994
TI  - Why doctors get angry in Crown Courts.

PMID- 11461995
TI  - A virally encoded chaperone specialized for folding of the major capsid protein
      of African swine fever virus.
AB  - It is generally believed that cellular chaperones facilitate the folding of virus
      capsid proteins, or that capsid proteins fold spontaneously. Here we show that
      p73, the major capsid protein of African swine fever virus (ASFV) failed to fold
      and aggregated when expressed alone in cells. This demonstrated that cellular
      chaperones were unable to aid the folding of p73 and suggested that ASFV may
      encode a chaperone. An 80-kDa protein encoded by ASFV, termed the capsid
      associated protein (CAP) 80, bound to the newly synthesized capsid protein in
      infected cells. The 80-kDa protein was released following conformational
      maturation of p73 and dissociated before capsid assembly. Coexpression of the 80
      kDa protein with p73 prevented aggregation and allowed the capsid protein to fold
      with kinetics identical to those seen in infected cells. CAP80 is, therefore, a
      virally encoded chaperone that facilitates capsid protein folding by masking
      domains exposed by the newly synthesized capsid protein, which are susceptible to
      aggregation, but cannot be accommodated by host chaperones. It is likely that
      these domains are ultimately buried when newly synthesized capsid proteins are
      added to the growing capsid shell.

PMID- 11461996
TI  - Hydrophobic amino acids in the human immunodeficiency virus type 1 p2 and
      nucleocapsid proteins can contribute to the rescue of deleted viral RNA packaging
      signals.
AB  - An RNA fragment of 75 nucleotides, which is located between the primer binding
      site and the 5' major splice donor site in human immunodeficiency virus type 1,
      has been shown to participate in specific encapsidation of viral RNA.
      Compensation studies have identified two second-site mutations, namely, MP2 (a
      T12I substitution in p2) and MNC (a T24I substitution in the nucleocapsid [NC]
      protein) that were involved in the rescue of various deletions in the
      aforementioned RNA region (i.e., BH-D1, BH-D2, and BH-LD3). To study whether the
      MP2 and MNC point mutations exert their compensatory effects in a cis manner,
      production of Gag proteins was blocked by insertion of stop codons into LD3, LD3
      MP2-MNC, and wild-type BH10 such that the constructs generated, i.e., LD3-DG, LD3
      MP2-MNC-DG, and BH-DG, only provided RNA transcripts for packaging. The results
      of cotransfection experiments showed that the LD3-MP2-MNC-DG viral RNA was
      packaged as inefficiently as LD3-DG; in contrast, BH-DG was efficiently packaged.
      Therefore, nucleotide substitutions in MP2 and MNC did not act in a cis manner to
      correct the packaging deficits in LD3. Next, we deliberately changed the T12 in
      p2 or the T24 in the NC to each of 19 other amino acids. We found that amino
      acids with long hydrophobic side chains, i.e., V, L, I, and M, were favored at
      either position 12 in p2 or at position 24 in NC to compensate for the above
      mentioned deletions. Further studies showed that only a few amino acids could not
      be used at these two sites by the wild-type virus due to decreased RNA levels in
      the virion or abnormal Gag protein processing. In this case, W, D, and E could
      not substitute for T12 in p2, and S, D, and N could not substitute for T24 in NC,
      without affecting viral infectivity. Therefore, the long hydrophobic side chains
      of V, L, I, and M are necessary for these amino acids to rescue the BH-D1, BH-D2,
      and BH-LD3 mutated viruses.

PMID- 11461997
TI  - Stability of the human papillomavirus type 18 E2 protein is regulated by a
      proteasome degradation pathway through its amino-terminal transactivation domain.
AB  - The E2 proteins of papillomaviruses regulate both viral transcription and DNA
      replication. The human papillomavirus type 18 (HPV18) E2 protein has been shown
      to repress transcription of the oncogenic E6 and E7 genes, inducing growth arrest
      in HeLa cells. Using HPV18 E2 fused to the green fluorescent protein (GFP), we
      showed that this protein was short-lived in transfected HeLa cells. Real-time
      microscopy experiments indicated that the E2-dependent signal increased for
      roughly 24 h after transfection and then rapidly disappeared, indicating that E2
      was unstable in HeLa cells and could confer instability to GFP. Similar studies
      done with a protein lacking the transactivation domain indicated that this
      truncation strongly stabilizes the E2 protein. In vitro, full-length E2 or the
      transactivation domain alone was efficiently ubiquitinated, whereas deletion of
      the transactivation domain strongly decreased the ubiquitination of the E2
      protein. Proteasome inhibition in cells expressing E2 increased its half-life
      about sevenfold, which was comparable to the half-life of the amino-terminally
      truncated protein. These characteristics of E2 instability were independent of
      the E2-mediated G(1) growth arrest in HeLa cells, as they were reproduced in MCF7
      cells, where E2 does not affect the cell cycle. Altogether, these experiments
      showed that the HPV18 E2 protein was degraded by the ubiquitin-proteasome pathway
      through its amino-terminal transactivation domain. Tight regulation of the
      stability of the HPV 18 E2 protein may be essential to avoid accumulation of a
      potent transcriptional repressor and antiproliferative agent during the viral
      vegetative cycle.

PMID- 11461998
TI  - Human immunodeficiency virus type 1 Vif protein is packaged into the
      nucleoprotein complex through an interaction with viral genomic RNA.
AB  - The human immunodeficiency virus type 1 (HIV-1) Vif protein plays a critical role
      in the production of infectious virions. Previous studies have demonstrated the
      presence of small amounts of Vif in virus particles. However, Vif packaging was
      assumed to be nonspecific, and its functional significance has been questioned.
      We now report that packaging of Vif is dependent on the packaging of viral
      genomic RNA in both permissive and restrictive HIV-1 target cells. Mutations in
      the nucleocapsid zinc finger domains that abrogate packaging of viral genomic RNA
      abolished packaging of Vif. Additionally, an RNA packaging-defective virus
      exhibited significantly reduced packaging of Vif. Finally, deletion of a putative
      RNA-interacting domain in Vif abolished packaging of Vif into virions. Virion
      associated Vif was resistant to detergent extraction and copurified with
      components of the viral nucleoprotein complex and functional reverse
      transcription complexes. Thus, Vif is specifically packaged into virions as a
      component of the viral nucleoprotein complex. Our data suggest that the specific
      association of Vif with the viral nucleoprotein complex might be functionally
      significant and could be a critical requirement for infectivity of viruses
      produced from restrictive host cells.

PMID- 11461999
TI  - Inhibition of human immunodeficiency virus type 1 transcription by chemical
      cyclin-dependent kinase inhibitors.
AB  - Cyclin-dependent kinases (cdk's) have recently been suggested to regulate human
      immunodeficiency virus type 1 (HIV-1) transcription. Previously, we have shown
      that expression of one cdk inhibitor, p21/Waf1, is abrogated in HIV-1 latently
      infected cells. Based on this result, we investigated the transcription of HIV-1
      in the presence of chemical drugs that specifically inhibited cdk activity and
      functionally mimicked p21/Waf1 activity. HIV-1 production in virally integrated
      lymphocytic and monocytic cell lines, such as ACH(2), 8E5, and U1, as well as
      activated peripheral blood mononuclear cells infected with syncytium-inducing
      (SI) or non-syncytium-inducing (NSI) HIV-1 strains, were all inhibited by
      Roscovitine, a purine derivative that reversibly competes for the ATP binding
      site present in cdk's. The decrease in viral progeny in the HIV-1-infected cells
      was correlated with a decrease in the transcription of HIV-1 RNAs in cells
      treated with Roscovitine and not with the non-cdk general cell cycle inhibitors,
      such as hydroxyurea (G(1)/S blocker) or nocodazole (M-phase blocker). Cyclin A-
      and E-associated histone H1 kinases, as well as cdk 7 and 9 activities, were all
      inhibited in the presence of Roscovitine. The 50% inhibitory concentration of
      Roscovitine on cdk's 9 and 7 was determined to be approximately 0.6 microM.
      Roscovitine could selectively sensitize HIV-1-infected cells to apoptosis at
      concentrations that did not impede the growth and proliferation of uninfected
      cells. Apoptosis induced by Roscovitine was found in both latent and activated
      infected cells, as evident by Annexin V staining and the cleavage of the PARP
      protein by caspase-3. More importantly, contrary to many apoptosis-inducing
      agents, where the apoptosis of HIV-1-infected cells accompanies production and
      release of infectious HIV-1 viral particles, Roscovitine treatment selectively
      killed HIV-1-infected cells without virion release. Collectively, our data
      suggest that cdk's are required for efficient HIV-1 transcription and, therefore,
      we propose specific cdk inhibitors as potential antiviral agents in the treatment
      of AIDS.

PMID- 11462000
TI  - Genetic retargeting of adenovirus: novel strategy employing "deknobbing" of the
      fiber.
AB  - For efficient and versatile use of adenovirus (Ad) as an in vivo gene therapy
      vector, modulation of the viral tropism is highly desirable. In this study, a
      novel method to genetically alter the Ad fiber tropism is described. The knob and
      the last 15 shaft repeats of the fiber gene were deleted and replaced with an
      external trimerization motif and a new cell-binding ligand, in this case the
      integrin-binding motif RGD. The corresponding recombinant fiber retained the
      basic biological functions of the natural fiber, i.e., trimerization, nuclear
      import, penton formation, and ligand binding. The recombinant fiber bound to
      integrins but failed to react with antiknob antibody. For virus production, the
      recombinant fiber gene was rescued into the Ad genome at the exact position of
      the wild-type (WT) fiber to make use of the native regulation of fiber
      expression. The recombinant virus Ad5/FibR7-RGD yielded plaques on 293 cells, but
      the spread through the monolayer was two to three times delayed compared to WT,
      and the ratio of infectious to physical particles was 20 times lower. Studies on
      virus tropism showed that Ad5/FibR7-RGD was able to infect cells which did not
      express the coxsackie-adenovirus receptor (CAR), but did express integrins.
      Ad5/FibR7-RGD virus infectivity was unchanged in the presence of antiknob
      antibody, which neutralized the WT virus. Ad5/FibR7-RGD virus showed an expanded
      tropism, which is useful when gene transfer to cells not expressing CAR is
      needed. The described method should also make possible the construction of Ad
      genetically retargeted via ligands other than RGD.

PMID- 11462001
TI  - Construction, safety, and immunogenicity in nonhuman primates of a chimeric
      yellow fever-dengue virus tetravalent vaccine.
AB  - We previously reported construction of a chimeric yellow fever-dengue type 2
      virus (YF/DEN2) and determined its safety and protective efficacy in rhesus
      monkeys (F. Guirakhoo et al., J. Virol. 74:5477-5485, 2000). In this paper, we
      describe construction of three additional YF/DEN chimeras using premembrane (prM)
      and envelope (E) genes of wild-type (WT) clinical isolates: DEN1 (strain PUO359,
      isolated in 1980 in Thailand), DEN3 (strain PaH881/88, isolated in 1988 in
      Thailand), and DEN4 (strain 1228, isolated in 1978 in Indonesia). These chimeric
      viruses (YF/DEN1, YF/DEN3, and YF/DEN4) replicated to ~7.5 log(10) PFU/ml in Vero
      cells, were not neurovirulent in 3- to 4-week-old ICR mice inoculated by the
      intracerebral route, and were immunogenic in monkeys. All rhesus monkeys
      inoculated subcutaneously with one dose of these chimeric viruses (as monovalent
      or tetravalent formulation) developed viremia with magnitudes similar to that of
      the YF 17D vaccine strain (YF-VAX) but significantly lower than those of their
      parent WT viruses. Eight of nine monkeys inoculated with monovalent YF/DEN1 -3,
      or -4 vaccine and six of six monkeys inoculated with tetravalent YF/DEN1-4
      vaccine seroconverted after a single dose. When monkeys were boosted with a
      tetravalent YF/DEN1-4 dose 6 months later, four of nine monkeys in the monovalent
      YF/DEN groups developed low levels of viremia, whereas no viremia was detected in
      any animals previously inoculated with either YF/DEN1-4 vaccine or WT DEN virus.
      An anamnestic response was observed in all monkeys after the second dose. No
      statistically significant difference in levels of neutralizing antibodies was
      observed between YF virus-immune and nonimmune monkeys which received the
      tetravalent YF/DEN1-4 vaccine or between tetravalent YF/DEN1-4-immune and
      nonimmune monkeys which received the YF-VAX. However, preimmune monkeys developed
      either no detectable viremia or a level of viremia lower than that in nonimmune
      controls. This is the first recombinant tetravalent dengue vaccine successfully
      evaluated in nonhuman primates.

PMID- 11462002
TI  - A human rotavirus with rearranged genes 7 and 11 encodes a modified NSP3 protein
      and suggests an additional mechanism for gene rearrangement.
AB  - A human rotavirus (isolate M) with an atypical electropherotype with 14 apparent
      bands of double-stranded RNA was isolated from a chronically infected
      immunodeficient child. MA-104 cell culture adaptation showed that the M isolate
      was a mixture of viruses containing standard genes (M0) or rearranged genes: M1
      (containing a rearranged gene 7) and M2 (containing rearranged genes 7 and 11).
      The rearranged gene 7 of virus M1 (gene 7R) was very unusual because it contained
      two complete open reading frames (ORF). Moreover, serial propagation of virus M1
      in cell culture indicated that gene 7R rapidly evolved, leading to a virus with a
      deleted gene 7R (gene 7RDelta). Gene 7RDelta coded for a modified NSP3 protein
      (NSP3m) of 599 amino acids (aa) containing a repetition of aa 8 to 296. The virus
      M3 (containing gene 7RDelta) was not defective in cell culture and actually
      produced NSP3m. The rearranged gene 11 (gene 11R) had a more usual pattern, with
      a partial duplication leading to a normal ORF followed by a long 3' untranslated
      region. The rearrangement in gene 11R was almost identical to some of those
      previously described, suggesting that there is a hot spot for gene rearrangements
      at a specific location on the sequence. It has been suggested that in some cases
      the existence of short direct repeats could favor the occurrence of rearrangement
      at a specific site. The computer modeling of gene 7 and 11 mRNAs led us to
      propose a new mechanism for gene rearrangements in which secondary structures,
      besides short direct repeats, might facilitate and direct the transfer of the RNA
      polymerase from the 5' to the 3' end of the plus-strand RNA template during the
      replication step.

PMID- 11462003
TI  - Contingent neutrality in competing viral populations.
AB  - The replicative fitness of a genetically marked (MARM-C) population of vesicular
      stomatitis virus was examined in competition assays in BHK-21 cells. In standard
      fitness assays involving up to eight competition passages of the mixed
      populations, MARM-C competes equally with the wild type (wt), but very prolonged
      competitions always led to the wt gaining dominance over MARM-C in a very slowed,
      nonlinear manner (J. Quer et al., J. Mol. Biol. 264:465-471, 1996). In the
      present study we show that a number of quite unrelated environmental
      perturbations, which decreased virus replication during competitions, all led to
      an accelerated dominance of the wt over MARM-C. These perturbations were (i) the
      presence of added (or endogenously generated) defective interfering particles,
      (ii) the presence of the chemical mutagen 5-fluorouracil (5-FU), or (iii) an
      increase in temperature to 40.5 degrees C. Thus, the "neutral fitness" of the
      MARM-C population is contingent. We have determined the entire genomic consensus
      sequence of MARM-C and have identified only six mutations. Clearly, some or all
      of these mutations allowed the MARM-C quasispecies population to compete equally
      with wt in a defined constant host environment, but the period of neutrality was
      shortened when the environment was perturbed during competitions. Interestingly,
      when four passages of each population were carried out independently in the
      presence of 5-FU (but in the absence of competition), no significant differences
      were detected in the fitness changes of wt and MARM-C, nor was there a difference
      in their subsequent abilities to compete with each other in a standard fitness
      assay. We propose a model for this contingent neutrality. The conditions employed
      to generate the MARM-C quasispecies population selected a small number of
      mutations in the consensus sequence. It appears that the MARM-C quasispecies
      population has moved into a segment of sequence space in which the average
      fitness value is neutral but, under environmental stress, beneficial mutations
      cannot be generated rapidly enough to compete with those being generated
      concurrently by competing wt virus quasispecies populations.

PMID- 11462004
TI  - Simian virus 40 Vp1 DNA-binding domain is functionally separable from the
      overlapping nuclear localization signal and is required for effective virion
      formation and full viability.
AB  - A DNA-binding domain (DBD) was identified on simian virus 40 (SV40) major capsid
      protein Vp1, and the domain's function in the SV40 life cycle was examined. The
      DBD was mapped by assaying various recombinant Vp1 proteins for DNA binding in
      vitro. The carboxy-terminal 58-residue truncated Vp1DeltaC58 pentamer bound DNA
      with a K(d) of 1.8 x 10(-9) M in terms of the protein pentamer, while full-length
      Vp1 and carboxy-terminal-17-truncated Vp1DeltaC17 had comparable apparent K(d)s
      of 5.3 x 10(-9) to 7.3 x 10(-9) M in terms of the protein monomers. Previously
      identified on Vp1 was a nuclear localization signal (NLS) consisting of two N
      terminal basic clusters, NLS1 (4-KRK-6) and NLS2 (15-KKPK-18). Vp1DeltaC58
      pentamers harboring multiple-point mutations in NLS1 (NLSm1), NLS2 (NLSm2), or
      both basic clusters (NLSm1. 2) had progressively decreased DNA-binding activity,
      down to 0.7% of the Vp1DeltaC58 level for NLSm1. 2 Vp1. These data, along with
      those of N-terminally truncated proteins, placed the DBD in overlap with the
      bipartite NLS. The role of the Vp1 DBD during infection was investigated by
      taking advantage of NLS phenotypic complementation (N. Ishii, A. Nakanishi, M.
      Yamada, M. H. Macalalad, and H. Kasamatsu, J. Virol. 68:8209-8216, 1994), in
      which an NLS-defective Vp1 could localize to the nucleus in the presence of wild
      type minor capsid proteins Vp2 and Vp3. This approach made it possible to dissect
      the role of the bifunctional Vp1 NLS-DBD in virion assembly in the nucleus.
      Mutants of the viable nonoverlapping SV40 (NO-SV40) DNA NLSm1, NLSm2, and NLSm1.
      2 replicated normally following transfection into host cells and produced capsid
      proteins at normal levels. All mutant Vp1s were able to interact with Vp3 in
      vitro. The mutants NLSm1 and NLSm1. 2 were nonviable, and the mutant Vp1s
      unexpectedly failed to localize to the nucleus though Vp2 and Vp3 did, suggesting
      that the mutated NLS1 acted as a dominant signal for the cytoplasmic localization
      of Vp1. Mutant NLSm2, for which the mutant Vp1's nuclear localization defect was
      complemented by Vp2 and Vp3, displayed a 5,000-fold reduced viability. Analysis
      of NLSm2 DNA-transfected cell lysate revealed a 10-fold reduction in the level of
      DNase I-protected viral DNA, and yet virion-like particles were found among the
      DNase I-resistant material. Collective results support a role for Vp1 NLS2-DBD2
      in the assembly of virion particles. The results also suggest that this
      determinant can function in the infection of new cells.

PMID- 11462005
TI  - Delivery of multiple epitopes by recombinant detoxified adenylate cyclase of
      Bordetella pertussis induces protective antiviral immunity.
AB  - CyaA, the adenylate cyclase toxin from Bordetella pertussis, can deliver its N
      terminal catalytic domain into the cytosol of a large number of eukaryotic cells
      and particularly into professional antigen-presenting cells. We have previously
      identified within the primary structure of CyaA several permissive sites at which
      insertion of peptides does not alter the ability of the toxin to enter cells.
      This property has been exploited to design recombinant CyaA toxoids capable of
      delivering major histocompatibility complex (MHC) class I-restricted CD8(+) T
      cell epitopes into antigen-presenting cells and to induce specific CD8(+)
      cytotoxic T-lymphocyte (CTL) responses in vivo. Here we have explored the
      capacity of the CyaA vector carrying several different CD8(+) T-cell epitopes to
      prime multiple CTL responses. The model vaccine consisted of a polyepitope made
      of three CTL epitopes from lymphocytic choriomeningitis virus (LCMV), the V3
      region of human immunodeficiency virus gp120, and chicken ovalbumin, inserted at
      three different sites of the catalytic domain of genetically detoxified CyaA.
      Each of these epitopes was processed on delivery by CyaA and presented in vitro
      to specific T-cell hybridomas. Immunization of mice by CyaA toxoids carrying the
      polyepitope lead to the induction of specific CTL responses for each of the three
      epitopes, as well as to protection against a lethal viral challenge. Moreover,
      mice primed against the vector by mock CyaA or a recombinant toxoid were still
      able to develop strong CTL responses after subsequent immunization with a
      recombinant CyaA carrying a foreign CD8(+) CTL epitope. These results highlight
      the potency of the adenylate cyclase vector for induction of protective CTL
      responses with multiple specificity and/or broad MHC restriction.

PMID- 11462006
TI  - Proteolysis of monomeric recombinant rotavirus VP4 yields an oligomeric VP5*
      core.
AB  - Rotavirus particles are activated for cell entry by trypsin cleavage of the outer
      capsid spike protein, VP4, into a hemagglutinin, VP8*, and a membrane penetration
      protein, VP5*. We have purified rhesus rotavirus VP4, expressed in baculovirus
      infected insect cells. Purified VP4 is a soluble, elongated monomer, as
      determined by analytical ultracentrifugation. Trypsin cleaves purified VP4 at a
      number of sites that are protected on the virion and yields a heterogeneous group
      of protease-resistant cores of VP5*. The most abundant tryptic VP5* core is
      trimmed past the N terminus associated with activation for virus entry into
      cells. Sequential digestion of purified VP4 with chymotrypsin and trypsin
      generates homogeneous VP8* and VP5* cores (VP8CT and VP5CT, respectively), which
      have the authentic trypsin cleavages in the activation region. VP8CT is a soluble
      monomer composed primarily of beta-sheets. VP5CT forms sodium dodecyl sulfate
      resistant dimers. These results suggest that trypsinization of rotavirus
      particles triggers a rearrangement in the VP5* region of VP4 to yield the dimeric
      spikes observed in icosahedral image reconstructions from electron cryomicroscopy
      of trypsinized rotavirus virions. The solubility of VP5CT and of trypsinized
      rotavirus particles suggests that the trypsin-triggered conformational change
      primes VP4 for a subsequent rearrangement that accomplishes membrane penetration.
      The domains of VP4 defined by protease analysis contain all mapped neutralizing
      epitopes, sialic acid binding residues, the heptad repeat region, and the
      membrane permeabilization region. This biochemical analysis of VP4 provides
      sequence-specific structural information that complements electron cryomicroscopy
      data and defines targets and strategies for atomic-resolution structural studies.

PMID- 11462007
TI  - Characterization of new syncytium-inhibiting monoclonal antibodies implicates
      lipid rafts in human T-cell leukemia virus type 1 syncytium formation.
AB  - We have previously shown that erythroleukemia cells (K562) transfected with
      vascular adhesion molecule 1 (VCAM-1) are susceptible to human T-cell leukemia
      virus type 1 (HTLV-1)-induced syncytium formation. Since expression of VCAM-1
      alone is not sufficient to render cells susceptible to HTLV-1 fusion, K562 cells
      appear to express a second molecule critical for HTLV-induced syncytium
      formation. By immunizing mice with K562 cells, we have isolated four monoclonal
      antibodies (MAbs), K5.M1, K5.M2, K5.M3, and K5.M4, that inhibit HTLV-induced
      syncytium formation between infected MT2 cells and susceptible K562/VCAM1 cells.
      These MAbs recognize distinct proteins on the surface of cells as determined by
      cell phenotyping, immunoprecipitation, and Western blot analysis. Since three of
      the proteins recognized by the MAbs appear to be GPI linked, we isolated lipid
      rafts and determined by immunoblot analysis that all four MAbs recognize proteins
      that sort entirely or in large part to lipid rafts. Dispersion of lipid rafts on
      the cells by cholesterol depletion with beta-cyclodextrin resulted in inhibition
      of syncytium formation, and this effect was not seen when the beta-cyclodextrin
      was preloaded with cholesterol before treating the cells. The results of these
      studies suggest that lipid rafts may play an important role in HTLV-1 syncytium
      formation.

PMID- 11462008
TI  - Downstream sequences influence the choice between a naturally occurring
      noncanonical and closely positioned upstream canonical heptameric fusion motif
      during bovine coronavirus subgenomic mRNA synthesis.
AB  - Mechanisms leading to subgenomic mRNA (sgmRNA) synthesis in coronaviruses are
      poorly understood but are known to involve a heptameric signaling motif,
      originally called the intergenic sequence. The intergenic sequence is the
      presumed crossover region (fusion site) for RNA-dependent RNA polymerase (RdRp)
      during discontinuous transcription, a process leading to sgmRNAs that are both 5'
      and 3' coterminal. In the bovine coronavirus, the major fusion site for synthesis
      of mRNA 5 (GGUAGAC) does not conform to the canonical motif (UC[U,C]AAAC) at
      three positions (underlined), yet it lies just 14 nucleotides downstream from
      such a sequence (UCCAAAC). The infrequently used canonical sequence, by computer
      prediction, is buried within the stem of a stable hairpin (-17.2 kcal/mol). Here
      we document the existence of this stem by enzyme probing and examine its
      influence and that of neighboring sequences on the unusual choice of fusion sites
      by analyzing transcripts made in vivo from mutated defective interfering RNA
      constructs. We learned that (i) mutations that were predicted to unfold the stem
      loop in various ways did not switch RdRp crossover to the upstream canonical
      site, (ii) a totally nonconforming downstream motif resulted in no measurable
      transcription from either site, (iii) the canonical upstream site does not
      function ectopically to lend competence to the downstream noncanonical site, and
      (iv) altering flanking sequences downstream of the downstream noncanonical motif
      in ways that diminish sequence similarity with the virus genome 5' end caused a
      dramatic switch to the upstream canonical site. These results show that sequence
      elements downstream of the noncanonical site can dramatically influence the
      choice of fusion sites for synthesis of mRNA 5 and are interpreted as being most
      consistent with a mechanism of similarity-assisted RdRp strand switching during
      minus-strand synthesis.

PMID- 11462009
TI  - Influenza B and C virus NEP (NS2) proteins possess nuclear export activities.
AB  - Nucleocytoplasmic transport of viral ribonucleoproteins (vRNPs) is an essential
      aspect of the replication cycle for influenza A, B, and C viruses. These viruses
      replicate and transcribe their genomes in the nuclei of infected cells. During
      the late stages of infection, vRNPs must be exported from the nucleus to the
      cytoplasm prior to transport to viral assembly sites on the cellular plasma
      membrane. Previously, we demonstrated that the influenza A virus nuclear export
      protein (NEP, formerly referred to as the NS2 protein) mediates the export of
      vRNPs. In this report, we suggest that for influenza B and C viruses the nuclear
      export function is also performed by the orthologous NEP proteins (formerly
      referred to as the NS2 protein). The influenza virus B and C NEP proteins
      interact in the yeast two-hybrid assay with a subset of nucleoporins and with the
      Crm1 nuclear export factor and can functionally replace the effector domain from
      the human immunodeficiency virus type 1 Rev protein. We established a plasmid
      transfection system for the generation of virus-like particles (VLPs) in which a
      functional viral RNA-like chloramphenicol acetyltransferase (CAT) gene is
      delivered to a new cell. VLPs generated in the absence of the influenza B virus
      NEP protein were unable to transfer the viral RNA-like CAT gene to a new cell.
      From these data, we suggest that the nuclear export of the influenza B and C
      vRNPs are mediated through interaction between NEP proteins and the cellular
      nucleocytoplasmic export machinery.

PMID- 11462010
TI  - Host range of small-ruminant lentivirus cytopathic variants determined with a
      selectable caprine arthritis- encephalitis virus pseudotype system.
AB  - The small-ruminant lentiviruses ovine maedi-visna virus (MVV) and caprine
      arthritis-encephalitis virus (CAEV) cause encephalitis, progressive pneumonia,
      arthritis, and mastitis in sheep and goats. Icelandic MVV strains, which are
      lytic in tissue culture, have a wide species distribution of functional
      receptors, which includes human cells. In contrast, functional receptors for the
      nonlytic CAEV CO are absent from human cells. To determine if the wide species
      distribution of functional receptors is a common property of MVV strains or
      related to cytopathic phenotype, we tested the infectivity of viruses pseudotyped
      with the envelope glycoproteins of MVV K1514, CAEV CO, and lytic and nonlytic
      North American MVV strains to cells of different species. Replication-defective
      CAEV proviral constructs lacking the env, tat, and vif genes and carrying the
      neomycin phosphotransferase gene in the vif-tat region were developed for the
      infectivity assays. Cotransfection of human 293T cells with these proviral
      constructs and plasmids expressing CAEV, MVV, or vesicular stomatitis virus
      envelope glycoproteins produced infectious pseudotyped virus which induced
      resistance of infected cells to G418. Using these pseudotypes, we confirmed the
      wide species distribution of Icelandic MVV receptors and the narrow host range of
      CAEV. However, functional receptors for the two North American MVV strains
      tested, unlike the Icelandic MVV and similar to CAEV, were limited to cells of
      ruminant species, regardless of cytopathic phenotype. The results indicate a
      differential receptor recognition by MVV strains which is unrelated to cytopathic
      phenotype.

PMID- 11462011
TI  - Role of metastability and acidic pH in membrane fusion by tick-borne encephalitis
      virus.
AB  - The envelope protein E of the flavivirus tick-borne encephalitis (TBE) virus is,
      like the alphavirus E1 protein, a class II viral fusion protein that differs
      structurally and probably mechanistically from class I viral fusion proteins. The
      surface of the native TBE virion is covered by an icosahedrally symmetrical
      network of E homodimers, which mediate low-pH-induced fusion in endosomes. At the
      pH of fusion, the E homodimers are irreversibly converted to a homotrimeric form,
      which we have found by intrinsic fluorescence measurements to be more stable than
      the native dimers. Thus, the TBE virus E protein is analogous to the prototypical
      class I fusion protein, the influenza virus hemagglutinin (HA), in that it is
      initially synthesized in a metastable state that is energetically poised to be
      converted to the fusogenic state by exposure to low pH. However, in contrast to
      what has been observed with influenza virus HA, this transition could not be
      triggered by input of heat energy alone and membrane fusion could be induced only
      when the virus was exposed to an acidic pH. In a previous study we showed that
      the dimer-to-trimer transition appears to be a two-step process involving a
      reversible dissociation of the dimer followed by an irreversible trimerization of
      the dissociated monomeric subunits. Because the dimer-monomer equilibrium in the
      first step apparently depends on the protonation state of E, the lack of
      availability of monomers for the trimerization step at neutral pH could explain
      why low pH is essential for fusion in spite of the metastability of the native E
      dimer.

PMID- 11462012
TI  - Two overlapping subdominant epitopes identified by DNA immunization induce
      protective CD8(+) T-cell populations with differing cytolytic activities.
AB  - Subdominant CD8(+) T-cell responses contribute to control of several viral
      infections and to vaccine-induced immunity. Here, using the lymphocytic
      choriomeningitis virus model, we demonstrate that subdominant epitopes can be
      more reliably identified by DNA immunization than by other methods, permitting
      the identification, in the virus nucleoprotein, of two overlapping subdominant
      epitopes: one presented by L(d) and the other presented by K(d). This subdominant
      sequence confers immunity as effective as that induced by the dominant epitope,
      against which >90% of the antiviral CD8(+) T cells are normally directed. We
      compare the kinetics of the dominant and subdominant responses after vaccination
      with those following subsequent viral infection. The dominant CD8(+) response
      expands more rapidly than the subdominant responses, but after virus infection is
      cleared, mice which had been immunized with the "dominant" vaccine have a pool of
      memory T cells focused almost entirely upon the dominant epitope. In contrast,
      after virus infection, mice which had been immunized with the "subdominant"
      vaccine retain both dominant and subdominant memory cells. During the acute phase
      of the immune response, the acquisition of cytokine responsiveness by subdominant
      CD8(+) T cells precedes their development of lytic activity. Furthermore, in both
      dominant and subdominant populations, lytic activity declines more rapidly than
      cytokine responsiveness. Thus, the lysis(low)-cytokine(competent) phenotype
      associated with most memory CD8(+) T cells appears to develop soon after antigen
      clearance. Finally, lytic activity differs among CD8(+) T-cell populations with
      different epitope specificities, suggesting that vaccines can be designed to
      selectively induce CD8(+) T cells with distinct functional attributes.

PMID- 11462013
TI  - Reconstitution of a functional duck hepatitis B virus replication initiation
      complex from separate reverse transcriptase domains expressed in Escherichia
      coli.
AB  - Hepatitis B viruses replicate through reverse transcription of an RNA
      intermediate, the pregenomic RNA (pgRNA). Replication is initiated de novo and
      requires formation of a ribonucleoprotein complex comprising the viral reverse
      transcriptase (P protein), an RNA stem-loop structure (epsilon) on the pgRNA, and
      cellular proteins, including the heat shock protein Hsp90, the cochaperone p23,
      and additional, as yet unknown, factors. Functional complexes catalyze the
      synthesis of a short DNA primer that is templated by epsilon and covalently
      linked to the terminal protein (TP) domain of P protein. Currently, the only
      system for generating such complexes in the test tube is in vitro translation of
      duck hepatitis B virus (DHBV) P protein in rabbit reticulocyte lysate (RRL),
      which also provides the necessary factors. However, its limited translation
      capacity precludes a closer analysis of the complex. To overcome this restriction
      we sought to produce larger amounts of DHBV P protein by expression in
      Escherichia coli, followed by complex reconstitution in RRL. Because previous
      attempts to generate full-length P protein in bacteria have failed we
      investigated whether separate expression of the TP and reverse transcriptase
      RNase H (RT-RH) domains would allow higher yields and whether these domains could
      trans complement each other. Indeed, TP and, after minor C-terminal
      modifications, also RT-RH could be expressed in substantial amounts, and when
      added to RRL, they were capable of epsilon-dependent DNA primer synthesis,
      demonstrating posttranslational activation. This reconstitution system should
      pave the way for a detailed understanding of the unique hepadnaviral replication
      initiation mechanism.

PMID- 11462014
TI  - High numbers of viral RNA copies in the central nervous system of mice during
      persistent infection with Theiler's virus.
AB  - The low-neurovirulence Theiler's murine encephalomyelitis viruses (TMEV), such as
      BeAn virus, cause a persistent infection of the central nervous system (CNS) in
      susceptible mouse strains that results in inflammatory demyelination. The ability
      of TMEV to persist in the mouse CNS has traditionally been demonstrated by
      recovering infectious virus from the spinal cord. Results of infectivity assays
      led to the notion that TMEV persists at low levels. In the present study, we
      analyzed the copy number of TMEV genomes, plus- to minus-strand ratios, and full
      length species in the spinal cords of infected mice and infected tissue culture
      cells by using Northern hybridization. Considering the low levels of infectious
      virus in the spinal cord, a surprisingly large number of viral genomes (mean of
      3.0 x 10(9)) was detected in persistently infected mice. In the transition from
      the acute (approximately postinfection [p.i.] day 7) to the persistent (beginning
      on p.i. day 28) phase of infection, viral RNA copy numbers steadily increased,
      indicating that TMEV persistence involves active viral RNA replication. Further,
      BeAn viral genomes were full-length in size; i.e., no subgenomic species were
      detected and the ratio of BeAn virus plus- to minus-strand RNA indicated that
      viral RNA replication is unperturbed in the mouse spinal cord. Analysis of
      cultured macrophages and oligodendrocytes suggests that either of these cell
      types can potentially synthesize high numbers of viral RNA copies if infected in
      the spinal cord and therefore account for the heavy viral load. A scheme is
      presented for the direct isolation of both cell types directly from infected
      spinal cords for further viral analyses.

PMID- 11462015
TI  - Reovirus-induced sigma1s-dependent G(2)/M phase cell cycle arrest is associated
      with inhibition of p34(cdc2).
AB  - Serotype 3 reoviruses inhibit cellular proliferation by inducing a G(2)/M phase
      cell cycle arrest. Reovirus-induced G(2)/M phase arrest requires the viral S1
      gene-encoded sigma1s nonstructural protein. The G(2)-to-M transition represents a
      cell cycle checkpoint that is regulated by the kinase p34(cdc2). We now report
      that infection with serotype 3 reovirus strain Abney, but not serotype 1 reovirus
      strain Lang, is associated with inhibition and hyperphosphorylation of p34(cdc2).
      The sigma1s protein is necessary and sufficient for inhibitory phosphorylation of
      p34(cdc2), since a viral mutant lacking sigma1s fails to hyperphosphorylate
      p34(cdc2) and inducible expression of sigma1s is sufficient for p34(cdc2)
      hyperphosphorylation. These studies establish a mechanism by which reovirus can
      perturb cell cycle regulation.

PMID- 11462016
TI  - Protection against simian immunodeficiency virus vaginal challenge by using Sabin
      poliovirus vectors.
AB  - Here we provide the first report of protection against a vaginal challenge with a
      highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector.
      New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were
      constructed, and these vectors were used to generate a series of new viruses
      containing SIV gag, pol, env, nef, and tat in overlapping fragments. Two
      cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) were
      inoculated into seven cynomolgus macaques. All monkeys produced substantial anti
      SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte
      responses were detected in three of seven monkeys after vaccination. All 7
      vaccinated macaques, as well as 12 control macaques, were challenged vaginally
      with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals
      exhibited substantial protection against the vaginal SIV challenge. All 12
      control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated
      monkeys we found no virological evidence of infection following challenge,
      indicating that these two monkeys were completely protected. Two additional SabRV
      SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to
      <10(3) copies/ml, suggesting that the vaccine elicited an effective cellular
      immune response. Three of six control animals developed clinical AIDS by 48 weeks
      postchallenge. In contrast, all seven vaccinated monkeys remained healthy as
      judged by all clinical parameters. These results demonstrate the efficacy of
      SabRV as a potential human vaccine vector, and they show that the use of a
      vaccine vector cocktail expressing an array of defined antigenic sequences can be
      an effective vaccination strategy in an outbred population.

PMID- 11462017
TI  - Identification of key amino acids of the mouse mammary tumor virus superantigen
      involved in the specific interaction with T-cell receptor V(beta) domains.
AB  - Mouse mammary tumor virus (MMTV) is a retrovirus encoding a superantigen that is
      recognized in association with major histocompatibility complex class II by the
      variable region of the beta chain (V(beta)) of the T-cell receptor. The C
      terminal 30 to 40 amino acids of the superantigen of different MMTVs display high
      sequence variability that correlates with the recognition of particular T-cell
      receptor V(beta) chains. Interestingly, MMTV(SIM) and mtv-8 superantigens are
      highly homologous but have nonoverlapping T-cell receptor V(beta) specificities.
      To determine the importance of these few differences for specific V(beta)
      interaction, we studied superantigen responses in mice to chimeric and mutant
      MMTV(SIM) and mtv-8 superantigens expressed by recombinant vaccinia viruses. We
      show that only a few changes (two to six residues) within the C terminus are
      necessary to modify superantigen recognition by specific V(beta)s. Thus, the
      introduction of the MMTV(SIM) residues 314-315 into the mtv-8 superantigen
      greatly decreased its V(beta)12 reactivity without gain of MMTV(SIM)-specific
      function. The introduction of MMTV(SIM)-specific residues 289 to 295, however,
      induced a recognition pattern that was a mixture of MMTV(SIM)- and mtv-8-specific
      V(beta) reactivities: both weak MMTV(SIM)-specific V(beta)4 and full mtv-8
      specific V(beta)11 recognition were observed while V(beta)12 interaction was
      lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8
      superantigen established normal MMTV(SIM)-specific V(beta)4 reactivity and
      completely abolished mtv-8-specific V(beta)5, -11, and -12 interactions. These
      new functional superantigens with mixed V(beta) recognition patterns allowed us
      to precisely delineate sites relevant for molecular interactions between the SIM
      or mtv-8 superantigen and the T-cell receptor V(beta) domain within the 30 C
      terminal residues of the viral superantigen.

PMID- 11462018
TI  - Identification of genotypic changes in human immunodeficiency virus protease that
      correlate with reduced susceptibility to the protease inhibitor lopinavir among
      viral isolates from protease inhibitor-experienced patients.
AB  - The association of genotypic changes in human immunodeficiency virus (HIV)
      protease with reduced in vitro susceptibility to the new protease inhibitor
      lopinavir (previously ABT-378) was explored using a panel of viral isolates from
      subjects failing therapy with other protease inhibitors. Two statistical tests
      showed that specific mutations at 11 amino acid positions in protease
      (L10F/I/R/V, K20M/R, L24I, M46I/L, F53L, I54L/T/V, L63P, A71I/L/T/V, V82A/F/T,
      I84V, and L90M) were associated with reduced susceptibility. Mutations at
      positions 82, 54, 10, 63, 71, and 84 were most closely associated with relatively
      modest (4- and 10-fold) changes in phenotype, while the K20M/R and F53L
      mutations, in conjunction with multiple other mutations, were associated with >20
      and >40-fold-reduced susceptibility, respectively. The median 50% inhibitory
      concentrations (IC(50)) of lopinavir against isolates with 0 to 3, 4 or 5, 6 or
      7, and 8 to 10 of the above 11 mutations were 0.8-, 2.7-, 13.5-, and 44.0-fold
      higher, respectively, than the IC(50) against wild-type HIV. On average, the
      IC(50) of lopinavir increased by 1.74-fold per mutation in isolates containing
      three or more mutations. Each of the 16 viruses that displayed a >20-fold change
      in susceptibility contained mutations at residues 10, 54, 63, and 82 and/or 84,
      along with a median of three mutations at residues 20, 24, 46, 53, 71, and 90.
      The number of protease mutations from the 11 identified in these analyses (the
      lopinavir mutation score) may be useful for the interpretation of HIV genotypic
      resistance testing with respect to lopinavir-ritonavir (Kaletra) regimens and may
      provide insight into the genetic barrier to resistance to lopinavir-ritonavir in
      both antiretroviral therapy-naive and protease inhibitor-experienced patients.

PMID- 11462019
TI  - Postnatal passive immunization of neonatal macaques with a triple combination of
      human monoclonal antibodies against oral simian-human immunodeficiency virus
      challenge.
AB  - To develop prophylaxis against mother-to-child human immunodeficiency virus (HIV)
      transmission, we established a simian-human immunodeficiency virus (SHIV)
      infection model in neonatal macaques that mimics intrapartum mucosal virus
      exposure (T. W. Baba et al., AIDS Res. Hum. Retroviruses 10:351-357, 1994). Using
      this model, neonates were protected from mucosal SHIV-vpu(+) challenge by pre-
      and postnatal treatment with a combination of three human neutralizing monoclonal
      antibodies (MAbs), F105, 2G12, and 2F5 (Baba et al., Nat. Med. 6:200-206, 2000).
      In the present study, we used this MAb combination only postnatally, thereby
      significantly reducing the quantity of antibodies necessary and rendering their
      potential use in humans more practical. We protected two neonates with this
      regimen against oral SHIV-vpu(+) challenge, while four untreated control animals
      became persistently infected. Thus, synergistic MAbs protect when used as
      immunoprophylaxis without the prenatal dose. We then determined in vitro the
      optimal MAb combination against the more pathogenic SHIV89.6P, a chimeric virus
      encoding env of the primary HIV89.6. Remarkably, the most potent combination
      included IgG1b12, which alone does not neutralize SHIV89.6P. We administered the
      combination of MAbs IgG1b12, 2F5, and 2G12 postnatally to four neonates. One of
      the four infants remained uninfected after oral challenge with SHIV89.6P, and two
      infants had no or a delayed CD4(+) T-cell decline. In contrast, all control
      animals had dramatic drops in their CD4(+) T cells by 2 weeks postexposure. We
      conclude that our triple MAb combination partially protected against mucosal
      challenge with the highly pathogenic SHIV89.6P. Thus, combination
      immunoprophylaxis with passively administered synergistic human MAbs may play a
      role in the clinical prevention of mother-to-infant transmission of HIV type 1.

PMID- 11462020
TI  - Human parainfluenza virus type 3 HN-receptor interaction: effect of 4-guanidino
      Neu5Ac2en on a neuraminidase-deficient variant.
AB  - The envelope of human parainfluenza virus type 3 (HPF3) contains two viral
      glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion protein (F).
      HN, which is responsible for receptor attachment and for promoting F-mediated
      fusion, also possesses neuraminidase (receptor-destroying) activity. We reported
      previously that 4-guanidino-neu5Ac2en (4-GU-DANA) and related sialic acid-based
      inhibitors of HPF3 neuraminidase activity also inhibit HN-mediated receptor
      binding and fusion processes not involving neuraminidase activity. We have now
      examined this mechanism, as well as neuraminidase's role in the viral life cycle,
      using a neuraminidase-deficient HPF3 variant (C28a) and stable cell lines
      expressing C28a or wild-type (wt) HN. C28a, which has a wt F sequence and two
      point mutations in the HN gene corresponding to two amino acid changes in the HN
      protein, is the first HPF3 variant with insignificant neuraminidase activity.
      Cells expressing C28a HN did not bind erythrocytes at 4 degrees C unless
      pretreated with neuraminidase, but no such pretreatment was required for
      hemadsorption activity (HAD) at 22 or 37 degrees C. HAD was blocked by 4-GU-DANA,
      attesting to the ability of this compound to inhibit HN's receptor-binding
      activity. C28a or wt plaque enlargement, a process that involves cell-cell fusion
      and does not depend on virion release, is diminished by the presence of 4-GU
      DANA, confirming the inhibitory effect of 4-GU-DANA on the fusogenic function of
      C28a HN. In C28a-infected cell monolayers, virion release and thus multicycle
      replication are severely restricted. This defect was corrected by supplementation
      of exogenous neuraminidase and also by the addition of 4-GU-DANA; neuraminidase
      destroys the receptors whereby newly formed C28a virions would remain attached to
      the cell surface, whereas 4-GU-DANA prevents the attachment itself, obviating the
      need for receptor cleavage. In accord with the ability of 4-GU-DANA to prevent
      attachment, the neuraminidase inhibitory effect of 4-GU-DANA on wt HPF3 did not
      diminish virion release into the medium. Thus, it is by inhibition of viral entry
      and syncytium formation that sialic acid analogs like 4-GU-DANA may counteract wt
      HPF3 infection.

PMID- 11462021
TI  - Efficient hepatitis delta virus RNA replication in avian cells requires a
      permissive factor(s) from mammalian cells.
AB  - Hepatitis delta virus (HDV) is a highly pathogenic human RNA virus whose genome
      is structurally related to those of plant viroids. Although its spread from cell
      to cell requires helper functions supplied by hepatitis B virus (HBV),
      intracellular HDV RNA replication can proceed in the absence of HBV proteins. As
      HDV encodes no RNA-dependent RNA polymerase, the identity of the (presumably
      cellular) enzyme responsible for this reaction remains unknown. Here we show
      that, in contrast to mammalian cells, avian cells do not support efficient HDV
      RNA replication and that this defect cannot be rescued by provision of HDV gene
      products in trans. Contrary to earlier assertions, this defect is not due to
      enhanced apoptosis triggered in avian cells by HDV. Fusion of avian cells to
      mammalian cells rescues HDV replication in avian nuclei, indicating that the
      nonpermissive phenotype of avian cells is not due to the presence of dominantly
      acting inhibitors of replication. Rather, avian cells lack one or more essential
      permissive factors present in mammalian cells. These results set the stage for
      the identification of such factors and also explain the failure of earlier
      efforts to transmit HDV infection to avian hosts harboring indigenous
      hepadnaviruses.

PMID- 11462022
TI  - Prolonged gray matter disease without demyelination caused by Theiler's murine
      encephalomyelitis virus with a mutation in VP2 puff B.
AB  - Theiler's murine encephalomyelitis virus (TMEV) is divided into two subgroups
      based on neurovirulence. During the acute phase, DA virus infects cells in the
      gray matter of the central nervous system (CNS). Throughout the chronic phase, DA
      virus infects glial cells in the white matter, causing demyelinating disease.
      Although GDVII virus also infects neurons in the gray matter, infected mice
      developed a severe polioencephalomyelitis, and no virus is detected in the white
      matter or other areas in the CNS in rare survivors. Several sequence differences
      between the two viruses are located in VP2 puff B and VP1 loop II, which are
      located near each other, close to the proposed receptor binding site. We
      constructed a DA virus mutant, DApBL2M, which has the VP1 loop II of GDVII virus
      and a mutation at position 171 in VP2 puff B. While DApBL2M virus replicated less
      efficiently than DA virus during the acute phase, DApBL2M-induced acute
      polioencephalitis was comparable to that in DA virus infection. Interestingly,
      during the chronic phase, DApBL2M caused prolonged gray matter disease in the
      brain without white matter involvement in the spinal cord. This is opposite what
      is observed during wild-type DA virus infection. Our study is the first to
      demonstrate that conformational differences via interaction of VP2 puff B and VP1
      loop II between GDVII and DA viruses can play an important role in making the
      transition of infection from the gray matter in the brain to the spinal cord
      white matter during TMEV infection.

PMID- 11462023
TI  - E1B 19K blocks Bax oligomerization and tumor necrosis factor alpha-mediated
      apoptosis.
AB  - Tumor necrosis factor alpha (TNF-alpha)-mediated death signaling causes the
      recruitment of monomeric pro- apoptotic Bax into a 500-kDa protein complex. The
      adenovirus Bcl-2 homologue, E1B 19K, inhibits TNF-alpha-mediated apoptosis,
      interacts with Bax, and blocked the formation of the 500-kDa Bax complex. TNF
      alpha and truncated Bid induced Bax-Bax cross-linking, indicative of
      oligomerization, and E1B 19K expression during infection inhibited this TNF-alpha
      mediated Bax oligomerization. TNF-alpha signaled conformation changes at the Bax
      amino and carboxy termini. Exposure of the Bax amino terminus facilitates E1B 19K
      Bax binding, which prevented exposure of the carboxy-terminal Bax Bcl-2 homology
      region 2 epitope. Inhibition of Bax oligomerization by E1B 19K is an activity
      that bears striking similarity to the means by which bacterial immunity proteins
      block pore formation by bacterial toxins which have structural homology to Bax.

PMID- 11462024
TI  - Human herpesvirus 8 envelope glycoprotein K8.1A interaction with the target cells
      involves heparan sulfate.
AB  - Human herpesvirus-8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus K8.1 gene
      encodes for two immunogenic glycoproteins, gpK8.1A and gpK8.1B, originating from
      spliced messages. The 228-amino-acid (aa) gpK8.1A is the predominant form
      associated with the virion envelope, consisting of a 167-aa region identical to
      gpK8.1B and a 61-aa unique region (L. Zhu, V. Puri, and B. Chandran, Virology
      262:237-249, 1999). HHV-8 has a broad in vivo and in vitro cellular tropism, and
      our studies showed that this may be in part due to HHV-8's interaction with the
      ubiquitous host cell surface molecule, heparan sulfate (HS). Since HHV-8 K8.1
      gene is positionally colinear to the Epstein-Barr virus (EBV) gene encoding the
      gp350/gp220 protein involved in EBV binding to the target cells, gpK8.1A's
      ability to interact with the target cells was examined. The gpK8.1A without the
      transmembrane and carboxyl domains (DeltaTMgpK8.1A) was expressed in a
      baculovirus system and purified. Radiolabeled purified DeltaTMgpK8.1A protein
      bound to the target cells, which was blocked by unlabeled DeltaTMgpK8.1A.
      Unlabeled DeltaTMgpK8.1A blocked the binding of [(3)H]thymidine-labeled purified
      HHV-8 to the target cells. Binding of radiolabeled DeltaTMgpK8.1A to the target
      cells was inhibited in a dose-dependent manner by soluble heparin, a
      glycosaminoglycan (GAG) closely related to HS, but not by other GAGs such as
      chondroitin sulfate A and C, N-acetyl heparin and de-N-sulfated heparin. Cell
      surface absorbed DeltaTMgpK8.1A was displaced by soluble heparin. Radiolabeled
      DeltaTMgpK8.1A also bound to HS expressing Chinese hamster ovary (CHO-K1) cells,
      and binding to mutant CHO cell lines deficient in HS was significantly reduced.
      The DeltaTMgpK8.1A specifically bound to heparin-agarose beads, which was
      inhibited by HS and heparin, but not by other GAGs. Virion envelope-associated
      gpK8.1A was specifically precipitated by heparin-agarose beads. These findings
      suggest that gpK8.1A interaction with target cells involves cell surface HS-like
      moieties, and HHV-8 interaction with HS could be in part mediated by virion
      envelope-associated gpK8.1A.

PMID- 11462025
TI  - Vaccinia virus F13L protein with a conserved phospholipase catalytic motif
      induces colocalization of the B5R envelope glycoprotein in post-Golgi vesicles.
AB  - The wrapping of intracellular mature vaccinia virions by modified trans-Golgi or
      endosomal cisternae to form intracellular enveloped virions is dependent on at
      least two viral proteins encoded by the B5R and F13L open reading frames. B5R is
      a type I integral membrane glycoprotein, whereas F13L is an unglycosylated,
      palmitylated protein with a motif that is conserved in a superfamily of
      phospholipid-metabolizing enzymes. Microscopic visualization of the F13L protein
      was achieved by fusing it to the enhanced green fluorescent protein (GFP). F13L
      GFP was functional when expressed by a recombinant vaccinia virus in which it
      replaced the wild-type F13L gene or by transfection of uninfected cells with a
      plasmid vector followed by infection with an F13L deletion mutant. In uninfected
      or infected cells, F13L-GFP was associated with Golgi cisternae and post-Golgi
      vesicles containing the LAMP 2 late endosomal-lysosomal marker. Association of
      F13L-GFP with vesicles was dependent on an intact phospholipase catalytic motif
      and sites of palmitylation. The B5R protein was also associated with LAMP2
      containing vesicles when F13L-GFP was coexpressed, but was largely restricted to
      Golgi cisternae in the absence of F13L-GFP or when the F13L moiety was mutated.
      We suggest that the F13L protein, like its human phospholipase D homolog,
      regulates vesicle formation and that this process is involved in intracellular
      enveloped virion membrane formation.

PMID- 11462026
TI  - Reactivation of latent human cytomegalovirus in CD14(+) monocytes is
      differentiation dependent.
AB  - We have previously demonstrated reactivation of latent human cytomegalovirus
      (HCMV) in myeloid lineage cells obtained from healthy donors. Virus was obtained
      from allogenically stimulated monocyte-derived macrophages (Allo-MDM), but not
      from macrophages differentiated by mitogenic stimulation (ConA-MDM). In the
      present study, the cellular and cytokine components essential for HCMV
      replication and reactivation were examined in Allo-MDM. The importance of both
      CD4(+) and CD8(+) T cells in the generation of HCMV-permissive Allo-MDM was
      demonstrated by negative selection or blocking experiments using antibodies
      directed against both HLA class I and HLA class II molecules. Interestingly,
      contact of monocytes with CD4 or CD8 T cells was not essential for reactivation
      of HCMV, since virus was observed in macrophages derived from CD14(+) monocytes
      stimulated by supernatants produced by allogeneic stimulation of peripheral blood
      mononuclear cells. Examination of the cytokines produced in Allo-MDM and ConA-MDM
      cultures indicated a significant difference in the kinetics of production and
      quantity of these factors. Further examination of the cytokines essential for the
      generation of HCMV-permissive Allo-MDM identified gamma interferon (IFN-gamma)
      but not interleukin-1 or -2, tumor necrosis factor alpha, or granulocyte
      macrophage colony-stimulating factor as critical components in the generation of
      these macrophages. In addition, although IFN-gamma was crucial for reactivation
      of latent HCMV, addition of IFN-gamma to unstimulated macrophage cultures was
      insufficient to reactivate virus. Thus, this study characterizes two distinct
      monocyte-derived cell types which can be distinguished by their ability to
      reactivate and support HCMV replication and identifies the critical importance of
      IFN-gamma in the reactivation of HCMV.

PMID- 11462027
TI  - Human parvovirus B19 induces cell cycle arrest at G(2) phase with accumulation of
      mitotic cyclins.
AB  - Human parvovirus B19 infects specifically erythroid progenitor cells, which
      causes transient aplastic crises and hemolytic anemias. Here, we demonstrate that
      erythroblastoid UT7/Epo cells infected with B19 virus fall into growth arrest
      with 4N DNA, indicating G(2)/M arrest. These B19 virus-infected cells displayed
      accumulation of cyclin A, cyclin B1, and phosphorylated cdc2 and were accompanied
      by an up-regulation in the kinase activity of the cdc2-cyclin B1 complex, similar
      to that in cells treated with the mitotic inhibitor. However, degradation of
      nuclear lamina and phosphorylation of histone H3 and H1 were not seen in B19
      virus-infected cells, indicating that the infected cells do not enter the M
      phase. Accumulation of cyclin B1 was persistently localized in the cytoplasm, but
      not in the nucleus, suggesting that B19 virus infection of erythroid cells raises
      suppression of nuclear import of cyclin B1, resulting in cell cycle arrest at the
      G(2) phase. The B19 virus-induced G(2)/M arrest may be the critical event in the
      damage of erythroid progenitor cells seen in patients with B19 virus infection.

PMID- 11462028
TI  - Cellular changes induced by low-risk human papillomavirus type 11 in
      keratinocytes that stably maintain viral episomes.
AB  - Infections by low-risk papillomavirus types, such as human papillomavirus (HPV)
      type 6 (HPV-6) and HPV-11, induce benign genital warts that rarely progress to
      malignancy. In contrast, lesions induced by high-risk HPV types have the
      potential to progress to cancer. Considerable information is available concerning
      the pathogenesis of high-risk HPV types, but little is known about the life cycle
      of low-risk HPV types. Although functionally distinct, both high- and low-risk
      virus types infect keratinocytes and induce virion production upon
      differentiation. This information suggests that they may share common mechanisms
      for regulating their productive life cycles. Using tissue culture methods
      developed to study high-risk HPV types, we examined the ability of HPV-11 to be
      stably maintained as episomes following transfection of normal human
      keratinocytes with cloned viral DNA. HPV-11 genomes were found to be maintained
      in keratinocytes for extended passages in cultures in 14 independent experiments
      involving transfection of cloned HPV-11 DNA. Interestingly, the HPV-11-positive
      cells exhibited an extended life span that averaged approximately twofold longer
      than that of control neomycin-transfected cells. In organotypic cultures, HPV-11
      positive cells exhibited altered differentiation patterns, but the extent of
      disruption was less severe than that seen with high-risk HPV types. In addition,
      the amplification of HPV-11 DNA, as well as the induction of several viral
      messages, was observed following differentiation of transfected cells in
      semisolid media. To determine whether global changes in cellular gene expression
      induced by HPV-11 were similar to those observed with high-risk HPV-31 (Y. E.
      Chang and L. A. Laimins, J. Virol. 74:4174-4182, 2000), microarray analysis of
      7,075 expressed sequences was performed. A spectrum of cellular genes different
      from that previously reported for HPV-31 was found to be activated or repressed
      by HPV-11. The expression of only a small set of genes was similarly altered by
      both high- and low-risk HPV types. This result suggests that different classes of
      HPVs have distinct effects on global cellular transcription patterns during
      infection. The methods described allow for a genetic analysis of HPV-11 in the
      context of its differentiation-dependent life cycle.

PMID- 11462029
TI  - Inhibition of p53 tumor suppressor by viral interferon regulatory factor.
AB  - The irreversible cell cycle arrest and apoptosis induced by p53 are part of the
      host surveillance mechanisms for viral infection and tumor induction. Kaposi's
      sarcoma-associated herpesvirus (KSHV), the most recently discovered human tumor
      virus, is associated with the pathogenesis of Kaposi's sarcoma, primary effusion
      lymphoma, and multicentric Castleman's disease. The K9 open reading frame of KSHV
      encodes a viral interferon (IFN) regulatory factor (vIRF) which functions as a
      repressor for cellular IFN-mediated signal transduction and as an oncoprotein to
      induce cell growth transformation. Here, we demonstrate that KSHV vIRF interacts
      with the cellular p53 tumor suppressor through the putative DNA binding region of
      vIRF and the central region of p53. This interaction suppresses the level of
      phosphorylation and acetylation of p53 and inhibits transcriptional activation of
      p53. As a consequence, vIRF efficiently prevents p53-mediated apoptosis. These
      results suggest that KSHV vIRF interacts with and inhibits the p53 tumor
      suppressor to circumvent host growth surveillance and to facilitate uncontrolled
      cell proliferation.

PMID- 11462030
TI  - Degradation of the retinoblastoma tumor suppressor by the human papillomavirus
      type 16 E7 oncoprotein is important for functional inactivation and is separable
      from proteasomal degradation of E7.
AB  - The steady-state level and metabolic half-life of retinoblastoma tumor suppressor
      protein pRB are decreased in cells that express high-risk human papillomavirus
      (HPV) E7 proteins. Here we show that pRB degradation is a direct activity of E7
      and does not reflect a property of cell lines acquired during the selection
      process for E7 expression. An amino-terminal domain of E7 that does not directly
      contribute to pRB binding but is required for transformation is also necessary
      for E7-mediated pRB degradation. Treatment with inhibitors of the 26S proteasome
      not only blocks E7-mediated pRB degradation but also causes the stabilization of
      E7. Mutagenic analyses, however, reveal that the processes of proteasomal
      degradation of E7 and pRB are not linked processes. HPV type 16 E7 also targets
      the pRB-related proteins p107 and p130 for destabilization by a proteasome
      dependent mechanism. Using the SAOS2 flat-cell assay as a biological indicator
      for pRB function, we demonstrate that pRB degradation, not solely binding, is
      important for the E7-induced inactivation of pRB.

PMID- 11462031
TI  - Requirement for uracil-DNA glycosylase during the transition to late-phase
      cytomegalovirus DNA replication.
AB  - Cytomegalovirus gene UL114, a homolog of mammalian uracil-DNA glycosylase (UNG),
      is required for efficient viral DNA replication. In quiescent fibroblasts, UNG
      mutant virus replication is delayed for 48 h and follows the virus-induced
      expression of cellular UNG. In contrast, mutant virus replication proceeds
      without delay in actively growing fibroblasts that express host cell UNG. In the
      absence of viral or host cell UNG expression, mutant virus fails to proceed to
      late-phase DNA replication, characterized by rapid DNA amplification. The data
      suggest that uracil incorporated early during wild-type viral DNA replication
      must be removed by virus or host UNG prior to late-phase amplification and
      encapsidation into progeny virions. The process of uracil incorporation and
      excision may introduce strand breaks to facilitate the transition from early
      phase replication to late-phase amplification.

PMID- 11462032
TI  - Human papillomavirus E6E7-mediated adenovirus cell killing: selectivity of mutant
      adenovirus replication in organotypic cultures of human keratinocytes.
AB  - Replication-competent adenoviruses are being investigated as potential anticancer
      agents. Exclusive virus replication in cancer cells has been proposed as a safety
      trait to be considered in the design of oncolytic adenoviruses. From this
      perspective, we have investigated several adenovirus mutants for their potential
      to conditionally replicate and promote the killing of cells expressing human
      papillomavirus (HPV) E6 and E7 oncoproteins, which are present in a high
      percentage of anogenital cancers. For this purpose, we have employed an
      organotypic model of human stratified squamous epithelium derived from primary
      keratinocytes that have been engineered to express HPV-18 oncoproteins stably. We
      show that, whereas wild-type adenovirus promotes a widespread cytopathic effect
      in all infected cells, E1A- and E1A/E1B-deleted adenoviruses cause no deleterious
      effect regardless of the coexpression of HPV18 E6E7. An adenovirus deleted in the
      CR2 domain of E1A, necessary for binding to the pRB family of pocket proteins,
      shows no selectivity of replication as it efficiently kills all normal and E6E7
      expressing keratinocytes. Finally, an adenovirus mutant deleted in the CR1 and
      CR2 domains of E1A exhibits preferential replication and cell killing in HPV E6E7
      expressing cultures. We conclude that the organotypic keratinocyte culture
      represents a distinct model to evaluate adenovirus selectivity and that, based on
      this model, further modifications of the adenovirus genome are required to
      restrict adenovirus replication to tumor cells.

PMID- 11462033
TI  - Recombinant measles viruses expressing altered hemagglutinin (H) genes:
      functional separation of mutations determining H antibody escape from
      neurovirulence.
AB  - Measles virus (MV) strain CAM/RB, which was adapted to growth in the brain of
      newborn rodents, is highly neurovirulent. It has been reported earlier that
      experimentally selected virus variants escaping from the monoclonal antibodies
      (MAbs) Nc32 and L77 to hemagglutinin (H) preserved their neurovirulence, whereas
      mutants escaping MAbs K71 and K29 were found to be strongly attenuated (U. G.
      Liebert et al., J. Virol. 68:1486-1493, 1994). To investigate the molecular basis
      of these findings, we have generated a panel of recombinant MVs expressing the H
      protein from CAM/RB and introduced the amino acid substitutions thought to be
      responsible for antibody escape and/or neurovirulence. Using these recombinant
      viruses, we identified the amino acid changes conferring escape from the MAbs L77
      (377R-->Q and 378M-->K), Nc32 (388G-->S), K71 (492E-->K and 550S-->P), and K29
      (535E-->G). When the corresponding recombinant viruses were tested in brains of
      newborn rodents, we found that the mutations mediating antibody escape did not
      confer differential neurovirulence. In contrast, however, replacement of two
      different amino acids, at positions 195G-->R and 200S-->N, which had been
      described for the escape mutant set, caused the change in neurovirulence. Thus,
      antibody escape and neurovirulence appear not to be associated with the same
      structural alterations of the MV H protein.

PMID- 11462034
TI  - Induction of potent human immunodeficiency virus type 1-specific T-cell
      restricted immunity by genetically modified dendritic cells.
AB  - A novel technology combining replication- and integration-defective human
      immunodeficiency virus type 1 (HIV-1) vectors with genetically modified dendritic
      cells was developed in order to induce T-cell immunity. We introduced the vector
      into dendritic cells as a plasmid DNA using polyethylenimine as the gene delivery
      system, thereby circumventing the problem of obtaining viral vector expression in
      the absence of integration. Genetically modified dendritic cells (GMDC) presented
      viral epitopes efficiently, secreted interleukin 12, and primed both CD4(+) and
      CD8(+) HIV-specific T cells capable of producing gamma interferon and exerting
      potent HIV-1-specific cytotoxicity in vitro. In nonhuman primates, subcutaneously
      injected GMDC migrated into the draining lymph node at an unprecedentedly high
      rate and expressed the plasmid DNA. The animals presented a vigorous HIV-specific
      effector cytotoxic-T-lymphocyte (CTL) response as early as 3 weeks after a single
      immunization, which later developed into a memory CTL response. Interestingly,
      antibodies did not accompany these CTL responses, indicating that GMDC can induce
      a pure Th1 type of immune response. Successful induction of a broad and long
      lasting HIV-specific cellular immunity is expected to control virus replication
      in infected individuals.

PMID- 11462035
TI  - The ribosome binding site of hepatitis C virus mRNA.
AB  - Hepatitis C virus (HCV) infects an estimated 170 million people worldwide, the
      majority of whom develop a chronic infection which can lead to severe liver
      disease, and for which no generally effective treatment yet exists. A promising
      target for treatment is the internal ribosome entry site (IRES) of HCV, a highly
      conserved domain within a highly variable RNA. Never before have the ribosome
      binding sites of any IRES domains, cellular or viral, been directly
      characterized. Here, we reveal that the HCV IRES sequences most closely
      associated with 80S ribosomes during protein synthesis initiation are a series of
      discontinuous domains together comprising by far the largest ribosome binding
      site yet discovered.

PMID- 11462036
TI  - Binding of human immunodeficiency virus type 1 gp120 to CXCR4 induces
      mitochondrial transmembrane depolarization and cytochrome c-mediated apoptosis
      independently of Fas signaling.
AB  - Apoptosis of CD4(+) T lymphocytes, induced by contact between human
      immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120) and its
      receptors, could contribute to the cell depletion observed in HIV-infected
      individuals. CXCR4 appears to play an important role in gp120-induced cell death,
      but the mechanisms involved in this apoptotic process remain poorly understood.
      To get insight into the signal transduction pathways connecting CXCR4 to
      apoptosis following gp120 binding, we used different cell lines expressing wild
      type CXCR4 and a truncated form of CD4 that binds gp120 but lacks the ability to
      transduce signals. The present study demonstrates that (i) the interaction of
      cell-associated gp120 with CXCR4-expressing target cells triggers a rapid
      dissipation of the mitochondrial transmembrane potential resulting in the
      cytosolic release of cytochrome c from the mitochondria to cytosol, concurrent
      with activation of caspase-9 and -3; (ii) this apoptotic process is independent
      of Fas signaling; and (iii) cooperation with a CD4 signal is not required. In
      addition, following coculture with cells expressing gp120, a Fas-independent
      apoptosis involving mitochondria and caspase activation is also observed in
      primary umbilical cord blood CD4(+) T lymphocytes expressing high levels of
      CXCR4. Thus, this gp120-mediated apoptotic pathway may contribute to CD4(+) T
      cell depletion in AIDS.

PMID- 11462037
TI  - Duck hepatitis B virus replication in primary bile duct epithelial cells.
AB  - Primary cultures of intrahepatic bile duct epithelial (IBDE) cells isolated from
      duckling livers were successfully grown for studies of duck hepatitis B virus
      (DHBV). The primary IBDE cells were characterized by immunohistochemistry using
      CAM 5.2, a cytokeratin marker which was shown to react specifically to IBDE cells
      in duck liver tissue sections and in primary cultures of total duck liver cells.
      Immunofluorescence assay using anti-duck albumin, a marker for hepatocytes,
      revealed that these IBDE cultures did not appear to contain hepatocytes. A
      striking feature of these cultures was the duct-like structures present within
      each cell colony of multilayered IBDE cells. Normal duck serum in the growth
      medium was found to be essential for the development of these cells into duct
      like structures. When the primary cultures of duck IBDE cells were acutely
      infected with DHBV, dual-labeled confocal microscopy using a combination of anti
      DHBV core proteins and CAM 5.2 or a combination of anti-pre-S1 proteins and CAM
      5.2 revealed that the IBDE cell colonies contained DHBV proteins. Immunoblot
      analysis of these cells showed that the DHBV pre-S1 and core proteins were
      similar to their counterparts in infected primary duck hepatocyte cultures.
      Southern blot analysis of infected IBDE preparations using a digoxigenin-labeled
      positive-sense DHBV riboprobe revealed the presence of hepadnavirus covalently
      closed circular (CCC) DNA, minus-sense single-stranded (SS) DNA, double-stranded
      linear DNA, and relaxed circular DNA. The presence of minus-sense SS DNA in the
      acutely infected IBDE cultures is indicative of DHBV reverse transcriptase
      activity, while the establishment of a pool of viral CCC DNA reveals the ability
      of these cells to maintain persistent infection. Taken collectively, the results
      from this study demonstrated that primary duck IBDE cells supported hepadnavirus
      replication as shown by the de novo synthesis of DHBV proteins and DNA
      replicative intermediates.

PMID- 11462038
TI  - Enhancement of muscle gene delivery with pseudotyped adeno-associated virus type
      5 correlates with myoblast differentiation.
AB  - Adeno-associated virus (AAV)-based muscle gene therapy has achieved tremendous
      success in numerous animal models of human diseases. Recent clinical trials with
      this vector have also demonstrated great promise. However, to achieve therapeutic
      benefit in patients, large inocula of virus will likely be necessary to establish
      the required level of transgene expression. For these reasons, efforts aimed at
      increasing the efficacy of AAV-mediated gene delivery to muscle have the
      potential for improving the safety and therapeutic benefit in clinical trials. In
      the present study, we compared the efficiency of gene delivery to mouse muscle
      cells for recombinant AAV type 2 (rAAV-2) and rAAV-2cap5 (AAV-2 genomes pseudo
      packaged into AAV-5 capsids). Despite similar levels of transduction by these two
      vectors in undifferentiated myoblasts, pseudotyped rAAV-2cap5 demonstrated
      dramatically enhanced transduction in differentiated myocytes in vitro (>500
      fold) and in skeletal muscle in vivo (>200-fold) compared to rAAV-2. Serotype
      specific differences in transduction efficiency did not directly correlate with
      viral binding to muscle cells but rather appeared to involve endocytic or
      intracellular barriers to infection. Furthermore, application of this pseudotyped
      virus in a mouse model of Duchenne's muscular dystrophy also demonstrated
      significantly improved transduction efficiency. These findings should have a
      significant impact on improving rAAV-mediated gene therapy in muscle.

PMID- 11462039
TI  - Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic virus
      type 1 p12(I): association with calreticulin and calnexin.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus encoding
      regulatory and accessory genes in four open reading frames (ORF I to IV) of the
      pX region. We have demonstrated an important role of pX ORF I expression, which
      encodes p12(I), in establishment of HTLV-1 infection in a rabbit model and for
      optimal viral infectivity in quiescent primary lymphocytes. These data indicated
      that p12(I) may enhance lymphocyte activation and thereby promote virus
      infection. To further define the role of p12(I) in cell activation, we
      characterized the subcellular localization of p12(I) in transfected 293T cells
      and HeLa-Tat cells by multiple methods, including immunofluorescence confocal
      microscopy, electron microscopy, and subcellular fractionation. Herein, we
      demonstrate that p12(I) accumulates in the endoplasmic reticulum (ER) and cis
      Golgi apparatus. The location of p12(I) was unchanged following treatments with
      both cycloheximide (blocking de novo protein synthesis) and brefeldin A
      (disrupting ER-to-Golgi protein transport), indicating that the protein is
      retained in the ER and cis-Golgi. Moreover, using coimmunoprecipitation assays,
      we identify the direct binding of p12(I) with both calreticulin and calnexin,
      resident ER proteins which regulate calcium storage. Our results indicate that
      p12(I) directly binds key regulatory proteins involved in calcium-mediated cell
      signaling and suggest a role of p12(I) in the establishment of HTLV-1 infection
      by activation of host cells.

PMID- 11462040
TI  - Accumulation and intranuclear distribution of unintegrated human immunodeficiency
      virus type 1 DNA.
AB  - The RNA genome of human immunodeficiency virus type 1 (HIV-1) is converted into
      DNA after infection in order to integrate into the host cell DNA. However, a
      large number of these reverse-transcribed genomes remain unintegrated in the
      nucleus of infected cells. Currently, there are no data available about the
      intranuclear distribution pattern of unintegrated HIV-1 DNA in relation to
      nuclear structures as observed on the single-cell level. In the present study, we
      investigated the intranuclear fate of unintegrated viral DNA in cell lines
      expressing CD4 and coreceptors (HOS-CD4.CCR5 and U373-MAGI-CXCR4(CEM)) infected
      with HIV-1 (strain 89.6). We used a novel approach to distinguish in situ
      unintegrated from integrated viral DNA by performing fluorescent in situ
      hybridization on cells in which stress-induced chromosome condensation had been
      induced, a procedure that contracts chromosomes independent of the cell cycle.
      Cells infected for 15 h accumulated large amounts of HIV-1 DNA which was located
      between the condensed chromosome strands, allowing the identification of this
      viral DNA as unintegrated. In contrast, in HeLa/LAV, a cell line carrying
      integrated HIV-1 genomes, the great majority of viral DNA colocalized with the
      cellular DNA. We show that unintegrated HIV-1 DNA does not evenly distribute
      within the host cell nucleus but tends to aggregate into clusters containing many
      copies of the viral genomes. The formation of these DNA clusters was independent
      of viral DNA replication and thus appeared to result solely from multiple
      infections. The DNA aggregates remained in the nuclei of infected cells for at
      least 25 h after the infection was stopped. The emergence of transcription sites,
      which most likely denote sites of the integrated provirus, lagged clearly behind
      the accumulation of viral DNA. These transcription foci could not be linked to
      unintegrated DNA molecules, suggesting that this DNA type is unable to
      transcribe, at least at levels comparable to those of integrated DNA. Neither
      unintegrated HIV-1 DNA nor transcription foci nor integrated DNA was observed to
      associate with nuclear domain 10 (ND10), a nuclear structure known to represent
      the site where several DNA viruses replicate and transcribe. Also, HIV-1 does not
      modify ND10 at early or late times of infection. There was no specific
      association of HIV-1 transcripts with splicing factor SC35 domains, in contrast
      to what has been reported for a number of both cellular and viral genes.
      Surprisingly, unintegrated HIV-1 DNA was found to accumulate within or in close
      association with SC35 domains, demonstrating a specific distribution of the viral
      DNA within the host cell nucleus. Taken together, our results demonstrate that
      unintegrated proviral HIV-1 DNA does not randomly localize within infected cells
      but preferentially aggregates in the nucleus within SC35 domains.

PMID- 11462041
TI  - Attenuation of Murray Valley encephalitis virus by site-directed mutagenesis of
      the hinge and putative receptor-binding regions of the envelope protein.
AB  - Molecular determinants of virulence in flaviviruses cluster in two regions on the
      three-dimensional structure of the envelope (E) protein; the base of domain II,
      believed to serve as a hinge during pH-dependent conformational change in the
      endosome, and the lateral face of domain III, which contains an integrin-binding
      motif Arg-Gly-Asp (RGD) in mosquito-borne flaviviruses and is believed to form
      the receptor-binding site of the protein. In an effort to better understand the
      nature of attenuation caused by mutations in these two regions, a full-length
      infectious cDNA clone of Murray Valley encephalitis virus prototype strain 1-51
      (MVE-1-51) was employed to produce a panel of site-directed mutants with
      substitutions at amino acid positions 277 (E-277; hinge region) or 390 (E-390;
      RGD motif). Viruses with mutations at E-277 (Ser-->Ile, Ser-->Asn, Ser-->Val, and
      Ser-->Pro) showed various levels of in vitro and in vivo attenuation dependent on
      the level of hydrophobicity of the substituted amino acid. Altered
      hemagglutination activity observed for these viruses suggests that mutations in
      the hinge region may indirectly disrupt the receptor-ligand interaction, possibly
      by causing premature release of the virion from the endosomal membrane prior to
      fusion. Similarly, viruses with mutations at E-390 (Asp-->Asn, Asp-->Glu, and Asp
      ->Tyr) were also attenuated in vitro and in vivo; however, the absorption and
      penetration rates of these viruses were similar to those of wild-type virus.
      This, coupled with the fact that E-390 mutant viruses were only moderately
      inhibited by soluble heparin, suggests that RGD-dependent integrin binding is not
      essential for entry of MVE and that multiple and/or alternate receptors may be
      involved in cell entry.

PMID- 11462042
TI  - Apical localization of the coxsackie-adenovirus receptor by glycosyl
      phosphatidylinositol modification is sufficient for adenovirus-mediated gene
      transfer through the apical surface of human airway epithelia.
AB  - In well-differentiated human airway epithelia, the coxsackie B and adenovirus
      type 2 and 5 receptor (CAR) resides primarily on the basolateral membrane. This
      location may explain the observation that gene transfer is inefficient when
      adenovirus vectors are applied to the apical surface. To further test this
      hypothesis and to investigate requirements and barriers to apical gene transfer
      to differentiated human airway epithelia, we expressed CAR in which the
      transmembrane and cytoplasmic tail were replaced by a glycosyl
      phosphatidylinositol (GPI) anchor (GPI-CAR). As controls, we expressed wild-type
      CAR and CAR lacking the cytoplasmic domain (Tailless-CAR). All three constructs
      enhanced gene transfer with similar efficiencies in fibroblasts. In airway
      epithelia, GPI-CAR localized specifically to the apical membrane, where it bound
      adenovirus and enhanced gene transfer to levels obtained when vector was applied
      to the basolateral membrane. Moreover, GPI-CAR facilitated gene transfer of the
      cystic fibrosis transmembrane conductance regulator to cystic fibrosis airway
      epithelia, correcting the Cl(-) transport defect. In contrast, when we expressed
      wild-type CAR it localized to the basolateral membrane and failed to increase
      apical gene transfer. Only a small amount of Tailless-CAR resided in the apical
      membrane, and the effects on apical virus binding and gene transfer were minimal.
      These data indicate that binding of adenovirus to an apical membrane receptor is
      sufficient to mediate effective gene transfer to human airway epithelia and that
      the cytoplasmic domain of CAR is not required for this process. The results
      suggest that targeting apical receptors in differentiated airway epithelia may be
      sufficient for gene transfer in the genetic disease cystic fibrosis.

PMID- 11462043
TI  - Centrosome abnormalities and genomic instability by episomal expression of human
      papillomavirus type 16 in raft cultures of human keratinocytes.
AB  - Primary human keratinocytes with ectopic expression of high-risk human
      papillomavirus (HPV) E6 and E7 oncoproteins display abnormal centrosome numbers,
      multipolar mitoses, and aneusomy. However, it has not been explored whether these
      abnormalities can occur in cells containing HPV episomes where E6 and E7
      expression is under viral transcriptional control. Here, we demonstrate that
      centrosome abnormalities and genomic instability occur in organotypic raft
      cultures of human keratinocytes with episomal HPV-16 even at low copy numbers. We
      conclude that HPV-16 DNA, when maintained as an episome, can disturb centrosome
      homeostasis and subvert genomic integrity of the host cell during early stages of
      the viral infection.

PMID- 11462044
TI  - Effective human herpesvirus 8 infection of human umbilical vein endothelial cells
      by cell-mediated transmission.
AB  - Cell-free transmission of human herpesvirus 8 (HHV-8) to human cells in vitro has
      been reported to be difficult, if not impossible. The present experiments were
      conducted with the idea that cell-cell contact may produce much more effective
      transmission, so-called cell-mediated transmission. Primary human umbilical vein
      endothelial cells (HUVECs) were cocultured with an HHV-8-infected lymphoma cell
      line, BCBL-1 cells. When a ratio of 12-O-tetradecanoylphorbol-13-acetate (TPA)
      treated BCBL-1 cells to HUVECs of 10:1 was used, more than 20% of HUVECs were
      found to express the HHV-8 latency-associated nuclear antigen (LANA) 48 h after
      the start of coculturing; this value increased to more than 30% after 72 h. HHV-8
      encoded ORF26, K8, K8.1, K10, K11, ORF59, and ORF65 proteins were not detected in
      these HHV-8-infected HUVECs until 72 h. The HHV-8 antigens were not observed in
      HUVECs cocultured with TPA-treated BCBL-1 cells separated by a membrane. Thirty
      days after removal of the BCBL-1 cells from the cell-mediated transmission
      experiment, the HUVECs still expressed LANA and the HHV-8 genome was detected by
      PCR in these cells. Moreover, the ORF59 protein, a DNA replication-associated
      protein of HHV-8, was expressed in such HUVECs in the presence of TPA
      stimulation. These results indicated a far more effective transmission mechanism,
      cell-cell contact, suggesting the possibility that such a mechanism works in
      vivo.

PMID- 11462045
TI  - Viral load increases in SJL/J mice persistently infected by Theiler's virus after
      inactivation of the beta(2)m gene.
AB  - We show that inactivating the beta(2)m gene increases the viral load of SJL/J
      mice persistently infected by Theiler's virus. Together with previous results,
      this shows that the characteristics of Tmevp1, a locus which controls the amount
      of viral RNA that persists in the central nervous system, are those of an H-2
      class I gene.

PMID- 11462046
TI  - DNA-induced structural changes in the papillomavirus capsid.
AB  - Human papillomavirus capsid assembly requires intercapsomeric disulfide bonds
      between molecules of the major capsid protein L1. Virions isolated from naturally
      occurring lesions have a higher degree of cross-linking than virus-like particles
      (VLPs), which have been generated in eukaryotic expression systems. Here we show
      that DNA encapsidation into VLPs leads to increased cross-linking between L1
      molecules comparable to that seen in virions. A higher trypsin resistance,
      indicating a tighter association of capsomeres through DNA interaction,
      accompanies this structural change.

PMID- 11462047
TI  - Phylogenetic analysis of enterovirus 71 strains isolated during linked epidemics
      in Malaysia, Singapore, and Western Australia.
AB  - Enterovirus 71 (EV71) is a frequent cause of hand, foot, and mouth disease (HFMD)
      epidemics associated with severe neurological sequelae in a small proportion of
      cases. There has been a significant increase in EV71 epidemic activity throughout
      the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have
      been associated with a severe form of brainstem encephalitis associated with
      pulmonary edema and high case fatality rates. In this study, we show that four
      genetic lineages of EV71 have been prevalent in the Asia-Pacific region since
      1997, including two previously undescribed genogroups (B3 and B4). Furthermore,
      we show that viruses belonging to genogroups B3 and B4 have circulated
      endemically in Southeast Asia during this period and have been the primary cause
      of several large HFMD or encephalitis epidemics in Malaysia, Singapore, and
      Western Australia.

PMID- 11462048
TI  - Tetramerization is a conserved feature of the virion-associated protein in plant
      pararetroviruses.
AB  - All plant pararetroviruses belong to the Caulimoviridae family. This family
      contains six genera of viruses with different biological, serological, and
      molecular characteristics. Although some important mechanisms of viral
      replication and host infection are understood, much remains to be discovered
      about the many functions of the viral proteins. The focus of this study, the
      virion-associated protein (VAP), is conserved among all members of the group and
      contains a coiled-coil structure that has been shown to assemble as a tetramer in
      the case of cauliflower mosaic virus. We have used the yeast two-hybrid system to
      characterize self-association of the VAPs of four distinct plant
      pararetroviruses, each belonging to a different genus of Caulimoviridae. Chemical
      cross-linking confirmed that VAPs assemble into tetramers. Tetramerization is
      thus a common property of these proteins in plant pararetroviruses. The possible
      implications of this conserved feature for VAP function are discussed.

PMID- 11462049
TI  - Analysis of virus-specific CD4(+) t cells during long-term gammaherpesvirus
      infection.
AB  - Major histocompatibility complex class II-mediated antigen presentation after
      intranasal infection with murine gammaherpesvirus 68 differs in mediastinal lymph
      nodes and spleen. Evidence that virus-specific CD4(+) T cells were being
      stimulated was found as late as 6 to 8 months after infection, and cells specific
      for the viral gp150(67-83) and ORF11(168-180) peptides were maintained as a
      fairly stable proportion of the total response.

PMID- 11462050
TI  - Physical and functional interactions between the corepressor CtBP and the Epstein
      Barr virus nuclear antigen EBNA3C.
AB  - CtBP has been shown to be a highly conserved corepressor of transcription. E1A
      and all the various transcription factors to which CtBP binds contain a conserved
      PLDLS CtBP-interacting domain, and EBNA3C includes a PLDLS motif (amino acids
      [aa] 728 to 732). Here we show that EBNA3C binds to CtBP both in vitro and in
      vivo and that the interaction requires an intact PLDLS. The C terminus of EBNA3C
      (aa 580 to 992) has modest trans-repressor activity when it is fused to the DNA
      binding domain of Gal4, and deletion or mutation of the PLDLS sequence ablates
      this and unmasks a transactivation function within the fragment. However, loss of
      the CtBP interaction motif had little effect on the ability of full-length EBNA3C
      to repress transcription. A striking correlation between CtBP binding and the
      capacity of EBNA3C to cooperate with (Ha-)Ras in the immortalization and
      transformation of primary rat embryo fibroblasts was also revealed.

PMID- 11462051
TI  - Use of patient-derived human immunodeficiency virus type 1 integrases to identify
      a protein residue that affects target site selection.
AB  - To identify parts of retroviral integrase that interact with cellular DNA, we
      tested patient-derived human immunodeficiency virus type 1 (HIV-1) integrases for
      alterations in the choice of nonviral target DNA sites. This strategy took
      advantage of the genetic diversity of HIV-1, which provided 75 integrase variants
      that differed by a small number of amino acids. Moreover, our hypothesis that
      biological pressures on the choice of nonviral sites would be minimal was
      validated when most of the proteins that catalyzed DNA joining exhibited altered
      target site preferences. Comparison of the sequences of proteins with the same
      preferences then guided mutagenesis of a laboratory integrase. The results showed
      that single amino acid substitutions at one particular residue yielded the same
      target site patterns as naturally occurring integrases that included these
      substitutions. Similar results were found with DNA joining reactions conducted
      with Mn(2+) or with Mg(2+) and were confirmed with a nonspecific alcoholysis
      assay. Other amino acid changes at this position also affected target site
      preferences. Thus, this novel approach has identified a residue in the central
      domain of HIV-1 integrase that interacts with or influences interactions with
      cellular DNA. The data also support a model in which integrase has distinct sites
      for viral and cellular DNA.

PMID- 11462052
TI  - Retroviral splicing suppressor requires three nonconsensus uridines in a 5'
      splice site-like sequence.
AB  - Rous sarcoma virus RNA contains a negative regulator of splicing (NRS) element
      that aids in maintenance of unspliced RNA. The NRS binds U1 snRNA at a sequence
      that deviates from the 5' splice site consensus by substitution of U's for A's at
      three positions: -2, +3, and +4. All three of these U's are important for NRS
      mediated splicing suppression. Substitution of a single nonconsensus C or G at
      any of these sites diminished NRS activity, whereas substitution of a single A
      generated a preferred 5' splice site within the NRS.

PMID- 11462053
TI  - Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are
      the most efficient blockers of virus adsorption to Vero cells.
AB  - The specific mechanisms by which antibodies neutralize flavivirus infectivity are
      not completely understood. To study these mechanisms in more detail, we analyzed
      the ability of a well-defined set of anti-dengue (DEN) virus E-glycoprotein
      specific monoclonal antibodies (MAbs) to block virus adsorption to Vero cells. In
      contrast to previous studies, the binding sites of these MAbs were localized to
      one of three structural domains (I, II, and III) in the E glycoprotein. The
      results indicate that most MAbs that neutralize virus infectivity do so, at least
      in part, by the blocking of virus adsorption. However, MAbs specific for domain
      III were the strongest blockers of virus adsorption. These results extend our
      understanding of the structure-function relationships in the E glycoprotein of
      DEN virus and provide the first direct evidence that domain III encodes the
      primary flavivirus receptor-binding motif.

PMID- 11462054
TI  - Role for p53 in gene induction by double-stranded RNA.
AB  - Cross talk between p53 and interferon-regulated pathways is implicated in the
      induction of gene expression by biologic and genotoxic stresses. We demonstrate
      that the interferon-stimulated gene ISG15 is induced by p53 and that p53 is
      required for optimal gene induction by double-stranded RNA (dsRNA), but not
      interferon. Interestingly, virus induces ISG15 in the absence of p53, suggesting
      that virus and dsRNA employ distinct signaling pathways.

PMID- 11462055
TI  - Sindbis virus variant with a deletion in the 6K gene shows defects in
      glycoprotein processing and trafficking: lack of complementation by a wild-type
      6K gene in trans.
AB  - A Sindbis virus (SV) variant with a 6K gene partially deleted has been obtained.
      This SV Del6K virus is defective in the proteolytic processing of virus
      glycoprotein precursor, transport of glycoproteins to the plasma membrane, and
      plaque phenotype. A revertant virus (SV Del6K-revQ21L) containing a point
      mutation in the deleted 6K gene was isolated and characterized. SV Del6K-revQ21L
      has corrected the defects of proteolytic processing and transport of virus
      glycoproteins to the plasma membrane, but it still remains attenuated compared to
      wild-type (wt) SV, exhibiting defects in virus budding. Neither mutant nor
      revertant viruses are complemented by the coexpression in trans of a wt SV 6K
      gene.

PMID- 11462056
TI  - Effect of soluble CD4 on exposure of epitopes on primary, intact, native human
      immunodeficiency virus type 1 virions of different genetic clades.
AB  - We have used a virus-binding assay to examine conformational changes that occur
      when soluble CD4 (sCD4) binds to the surface of intact, native, primary human
      immunodeficiency virus type 1 virions. The isolates examined belong to seven
      genetic clades (A to H) and are representative of syncytium-inducing and non
      syncytium-inducing phenotypes. Conformational changes in epitopes in the C2, V2,
      V3, C5, and CD4 binding domain (CD4bd) of gp120 and the cluster I and II regions
      of gp41 of these viruses were examined using human monoclonal antibodies that are
      directed at these regions. The studies revealed that sCD4 binding causes a marked
      increase in exposure of epitopes in the V3 loop, irrespective of the clade or the
      phenotype of the virus. Sporadic increases in exposure were observed in some
      epitopes in the V2 region, while no changes were observed in the C2, C5, or CD4bd
      of gp120 or the cluster I and II regions of gp41.

PMID- 11462058
TI  - Antidepressants in the treatment of patients with COPD: possible associations
      between smoking cigarettes, COPD and depression.

PMID- 11462059
TI  - Asthma in preschool children: prevalence and risk factors.
AB  - BACKGROUND: The prevalence of asthma in children has increased in many countries
      over recent years. To plan effective interventions to reverse this trend we need
      a better understanding of the risk factors for asthma in early life. This study
      was undertaken to measure the prevalence of, and risk factors for, asthma in
      preschool children. METHODS: Parents of children aged 3-5 years living in two
      cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were
      surveyed by questionnaire to ascertain the presence of asthma and various
      proposed risk factors for asthma in their children. Recent asthma was defined as
      ever having been diagnosed with asthma and having cough or wheeze in the last 12
      months and having used an asthma medication in the last 12 months. Atopy was
      measured by skin prick tests to six common allergens. RESULTS: The prevalence of
      recent asthma was 22% in Lismore and 18% in Wagga Wagga. Factors which increased
      the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to
      3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16),
      having had a serious respiratory infection in the first 2 years of life (OR 1.93,
      95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03,
      95% CI 1.15 to 3.60). Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having
      three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of
      recent asthma. CONCLUSIONS: Of the factors tested, those that have the greatest
      potential to be modified to reduce the risk of asthma are breast feeding and
      consumption of polyunsaturated fats.

PMID- 11462060
TI  - Nitrogen dioxide exposure from domestic gas cooking and airway response in
      asthmatic women.
AB  - BACKGROUND: Previous studies have not found a consistent association between
      exposure to domestic cooking using gas appliances and exacerbation of asthma. We
      investigated the immediate airflow response to acute exposure from single
      episodes of gas cooking, and peak airflow variability from continued exposure to
      repeated episodes of gas cooking in a group of non-smoking asthmatic women.
      METHODS: Sixteen adult non-smoking women with mild to severe persistent asthma
      were studied. The acute short term level of nitrogen dioxide (NO2) during gas
      cooking episodes and the mean exposure to NO2 from repeated gas cooking episodes
      were measured over a 2 week period, as well as proxy measures of frequency of
      cooking on each day and the length of time spent cooking each day. Their asthma
      status was monitored using peak expiratory flow rates (PEFR) before and after
      cooking, 2 week self-recorded serial readings of PEFR, respiratory symptom
      severity score, and use of rescue bronchodilators for acute asthma attacks.
      RESULTS: Cooking was significantly associated with an immediate mean fall in PEFR
      of 3.4% (p=0.015, paired t test). The acute short term NO2 level during cooking
      was significantly correlated with the fall in PEFR (r=-0.579; p=0.019). The
      frequency of cooking over a 2 week period was positively correlated with the mean
      exposure to NO2 (r=0.529; p=0.042). Continued exposure to NO2 over a 2 week
      period was associated significantly with increased frequency of rescue
      bronchodilator usage for asthma attacks (r=0.597; p=0.031). However, it was
      negatively associated with PEFR variability (r=-0.512; p=0.051) and respiratory
      symptom severity score (r= -0.567; p=0.043), probably due to the masking effects
      of bronchodilator treatment. CONCLUSIONS: Acute short term exposure to NO2 from
      single episodes of gas cooking is associated with immediate airflow limitation.
      Continued exposure from repeated episodes of gas cooking in asthmatic women is
      associated with greater use of rescue bronchodilators.

PMID- 11462061
TI  - Effect of nebulised L- and D-arginine on exhaled nitric oxide in steroid naive
      asthma.
AB  - BACKGROUND: Nitric oxide (NO) is a product of the enzyme nitric oxide synthase
      (NOS) and is found in normal and asthmatic human airways. The administration of L
      arginine results in an increase in airway NO production in asthmatic subjects.
      This is thought to occur because L-arginine is the substrate for NOS. However,
      studies in the systemic vasculature suggest that other mechanisms may be
      responsible. METHODS: Eight patients with steroid naive asthma each received 2.5
      g L-arginine, 2.5 g D-arginine, and 2.0% saline by ultrasonic nebuliser on
      separate days in a randomised, single blind manner. Exhaled NO was measured by
      chemiluminescence and spirometric tests were performed before and for 3 hours
      after each administration. The mean concentration of NO after exposure was
      calculated from the area under the curve. RESULTS: L-arginine, D-arginine, and
      2.0% saline induced a mean (95% CI) maximal bronchoconstriction of 11.9% (-1.7 to
      25.4), 10.0% (2.8 to 17.2), and 8.5% (-2.5 to 19.5) of the starting forced
      expiratory volume in one second (FEV(1)), respectively. Exhaled NO declined in
      proportion to the degree of bronchoconstriction (r=0.60, p<0.01).
      Bronchoconstriction and the acute reduction in exhaled NO resolved within 15
      minutes. The mean post-exposure concentration of NO was 15.75 parts per billion
      (ppb) after L-arginine, 15.16 ppb after D-arginine, and 12.74 ppb after 2.0%
      saline. The mean (95% CI) difference between L-arginine and placebo was 3.01
      (0.32 to 5.7) ppb, between D-arginine and placebo 2.42 (0.10 to 4.74) ppb, and
      between L- and D-arginine 0.59 (-1.56 to 2.74) ppb. CONCLUSIONS: Exhaled NO
      decreased with acute bronchoconstriction and returned to baseline with the
      resolution of bronchoconstriction. Exhaled NO increased following the
      administration of both L-arginine and D-arginine. Since NOS is stereospecific,
      this finding suggests that the increase in exhaled NO is not entirely mediated
      through an increase in NOS enzyme activity. We suggest that arginine may react in
      a non-stereospecific fashion with reactive oxygen species present in asthmatic
      airways.

PMID- 11462062
TI  - Respiratory symptoms, asthma, exercise test spirometry, and atopy in
      schoolchildren from a Lima shanty town.
AB  - BACKGROUND: Little is known about the associations between symptoms of asthma,
      pulmonary function tests, and atopy in developing countries. While asthma in
      children is often associated with atopy, some studies of wheezing illness have
      found little or no association, leading to suggestions that there are subgroups
      of wheezing illness. The ISAAC study recently reported that the prevalence of
      reported asthma symptoms in Lima, Peru was among the highest in the world, but
      did not report on the atopic status of the subjects. METHODS: A cross sectional
      survey was conducted of children aged 8-10 years who had previously participated
      in a cohort study of respiratory and diarrhoeal illnesses in infancy.
      Questionnaires were administered asking about respiratory symptoms and asthma
      diagnoses, pulmonary function tests were performed before and after exercise on a
      treadmill, and atopy was determined from skin prick tests and specific serum IgE
      levels. RESULTS: A total of 793 children participated in the survey. The
      prevalence of asthma related symptoms in the last 12 months was 23.2%, but only
      3.8% of children reported a recent asthma attack. The mean differences in pretest
      percentage predicted forced expiratory volume in one second (FEV(1)) were 8.1%
      (95% CI 2.4 to 13.8) between children who did and did not report an asthma attack
      in the last 12 months, and 5.3% (95% CI 2.8 to 7.9) in children who did and did
      not report respiratory symptoms. The corresponding differences in mean percentage
      fall in FEV(1) after exercise were 3.1% (95% CI -1 to 7.1) and 5.1% (95% CI 3.4
      to 6.8). Recent asthma or respiratory symptoms were not associated with atopy in
      this population (odds ratios 1.29 (95% CI 0.56 to 2.97) and 0.91 (95% CI 0.61 to
      1.37), respectively). CONCLUSIONS: Most asthma in these children was unrecognised
      and mild. Asthma and asthma symptoms in this population do not seem to be related
      to atopy.

PMID- 11462063
TI  - Exogenous female sex steroid hormones and risk of asthma and asthma-like
      symptoms: a cross sectional study of the general population.
AB  - BACKGROUND: Recent evidence suggests a role for hormonal factors in the aetiology
      of asthma. METHODS: Data from a large study of women selected from the general
      population were used to relate treatment with oral hormonal contraceptives (OCP)
      and postmenopausal hormone replacement therapy (HRT) to the following asthma
      indicators: self-reported asthma, wheezing, cough at exertion, and use of
      medication for asthma. The study sample comprised 1536 premenopausal and 3016
      postmenopausal women who participated in the third round of the Copenhagen City
      Heart Study in 1991-4. A total of 377 women were taking OCP (24.5% of
      premenopausal women) and 458 were on HRT (15.2% of postmenopausal women).
      RESULTS: In premenopausal women 4.8% reported having asthma. The prevalence of
      self-reported asthma, wheeze, use of asthma medication, and cough at exertion was
      not significantly related to use of OCP. In postmenopausal women the prevalence
      of self-reported asthma was 6.2%. A weak but consistent association was observed
      between HRT and self-reported asthma (OR 1.42 (95% CI 0.95 to 2.12)), wheeze (OR
      1.29 (95% CI 1.02 to 1.64)), cough at exertion (OR 1.34 (95% CI 1.01 to 1.77)),
      and use of asthma medication (OR 1.45 (95% CI 0.97 to 2.18)). CONCLUSIONS: In
      this study of the general population no relationship was found between the use of
      OCP and asthma. Although an association was observed between HRT and asthma and
      asthma-like symptoms, this was relatively weak and it is concluded that there is
      no necessity to change present prescription practice.

PMID- 11462064
TI  - Bedside tracer gas technique accurately predicts outcome in aspiration of
      spontaneous pneumothorax.
AB  - BACKGROUND: There is no technique in general use that reliably predicts the
      outcome of manual aspiration of spontaneous pneumothorax. We have hypothesised
      that the absence of a pleural leak at the time of aspiration will identify a
      group of patients in whom immediate discharge is unlikely to be complicated by
      early lung re-collapse and have tested this hypothesis by using a simple bedside
      tracer gas technique. METHODS: Eighty four episodes of primary spontaneous
      pneumothorax and 35 episodes of secondary spontaneous pneumothorax were studied
      prospectively. Patients breathed air containing a tracer (propellant gas from a
      pressurised metered dose inhaler) while the pneumothorax was aspirated
      percutaneously. Tracer gas in the aspirate was detected at the bedside using a
      portable flame ioniser and episodes were categorised as tracer gas positive (>1
      part per million of tracer gas) or negative. The presence of tracer gas was taken
      to imply a persistent pleural leak. Failure of manual aspiration and the need for
      a further intervention was based on chest radiographic appearances showing either
      failure of the lung to re-expand or re-collapse following initial re-expansion.
      RESULTS: A negative tracer gas test alone implied that manual aspiration would be
      successful in the treatment of 93% of episodes of primary spontaneous
      pneumothorax (p<0.001) and in 86% of episodes of secondary spontaneous
      pneumothorax (p=0.01). A positive test implied that manual aspiration would
      either fail to re-expand the lung or that early re-collapse would occur despite
      initial re-expansion in 66% of episodes of primary spontaneous pneumothorax and
      71% of episodes of secondary spontaneous pneumothorax. Lung re-inflation on the
      chest radiograph taken immediately after aspiration was a poor predictor of
      successful aspiration, with lung re-collapse occurring in 34% of episodes by the
      following day such that a further intervention was required. CONCLUSIONS:
      National guidelines currently recommend immediate discharge of patients with
      primary spontaneous pneumothorax based primarily on the outcome of the post
      aspiration chest radiograph which we have shown to be a poor predictor of early
      lung re-collapse. Using a simple bedside test in combination with the post
      aspiration chest radiograph, we can predict with high accuracy the success of
      aspiration in achieving sustained lung re-inflation, thereby identifying patients
      with primary spontaneous pneumothorax who can be safely and immediately
      discharged home and those who should be observed overnight because of a
      significant risk of re-collapse, with an estimated re-admission rate of 1%.

PMID- 11462065
TI  - Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high
      resolution computed tomography, chest radiography, and pulmonary function tests.
AB  - BACKGROUND: Fibrosing alveolitis (FA) is a common and serious complication of
      rheumatoid arthritis (RA). Before the availability of high resolution computed
      tomographic (HRCT) scanning, it was difficult to diagnose accurately without
      recourse to biopsy. Prospective studies have reported a prevalence of
      interstitial lung disease (ILD) of 19-44%. The term ILD used by these authors
      encompasses a variety of appearances on HRCT scans. This prospective study used
      HRCT scanning to determine the true prevalence of FA in hospital outpatients with
      RA, and to study associated clinical characteristics. METHODS: One hundred and
      fifty consecutive patients with RA were selected from a hospital outpatient
      department, irrespective of the presence or absence of chest disease. All
      underwent a detailed clinical assessment, chest HRCT scanning, and conventional
      chest radiography within 4 weeks of full pulmonary function tests. RESULTS:
      Seventy percent of patients were current or reformed cigarette smokers. Twenty
      eight (19%) had FA, most frequently of reticular pattern, and 12 of this group
      (43%) also had emphysematous bullae. None of the previously suggested risk
      factors for developing FA were confirmed. Fifty four percent of patients with
      HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon
      monoxide transfer factor (TLCO), 14% had restrictive pulmonary function tests,
      and 14% had bilateral chest radiographic signs of FA. CONCLUSIONS: HRCT evidence
      of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest
      examination or on full pulmonary function tests, even without restrictive changes
      or chest radiographic abnormalities, should prompt physicians to request a chest
      HRCT scan when investigating dyspnoea in patients with RA.

PMID- 11462066
TI  - Radical radiotherapy for stage I/II non-small cell lung cancer in patients not
      sufficiently fit for or declining surgery (medically inoperable): a systematic
      review.
AB  - OBJECTIVES: To determine the effectiveness of radical radiotherapy in medically
      inoperable stage I/II non-small cell lung cancer (NSCLC) and the extent of
      treatment related morbidity. METHODS: Randomised trials were sought by
      electronically searching the Cochrane Clinical Trials Register, and both
      randomised and non-randomised trials were sought by searching Medline and
      Excerpta Medica (Embase). Further studies were identified from references cited
      in those papers already identified by electronic searching. The studies included
      were those of patients of any age with stage I/II NSCLC receiving radiotherapy at
      a dose of >40 Gy in 20 fractions over 4 weeks or its radiobiological equivalent.
      RESULTS: Two randomised and 35 non-randomised studies were identified. One
      randomised and nine non-randomised studies did not meet the selection criteria,
      leaving one randomised and 26 non-randomised studies for analysis. In the
      randomised trial 2 year survival was higher following continuous
      hyperfractionated accelerated radiotherapy (CHART; 37%) than following 60 Gy in
      30 fractions over 6 weeks (24%). An estimated 2003 patients were included in the
      26 non-randomised studies; overall survival was 22-72% at 2 years, 17-55% at 3
      years, and 0-42% at 5 years. Following treatment, 11-43% of patients died from
      causes other than cancer. Cancer specific survival was 54-93% at 2 years, 22-56%
      at 3 years, and 13-39% at 5 years. Complete response rates were 33-61% and local
      failure rates were 6-70%. Distant metastases developed in approximately 25% of
      patients. Better response rates and survival were seen in those with smaller
      tumours and in those receiving higher doses although the reasons for prescribing
      higher doses were not clearly stated. The outcome was worse in those with prior
      weight loss or poor performance status. Assessment of treatment related morbidity
      and effects on quality of life and symptom control were inconclusive because of
      the lack of prospective evaluation and paucity of data. CONCLUSIONS: No
      randomised trials compared a policy of immediate radical radiotherapy with
      palliative radiotherapy given when patients develop symptoms. In the absence of
      such trials, radical radiotherapy appears to result in a better survival than
      might be expected had treatment not been given. A substantial, though variable,
      proportion of patients died during follow up from causes other than cancer. The
      optimal radiation dose and treatment technique (particularly with respect to
      mediastinal irradiation) remain uncertain.

PMID- 11462067
TI  - Prognostic value of CD4+ lymphocytes in pleural cavity of patients with non-small
      cell lung cancer.
AB  - BACKGROUND: For patients with non-small cell lung cancer the TNM staging system
      and other conventional prognostic factors fail to predict accurately the outcome
      of treatment and survival. This study attempts to determine the prognostic value
      for survival of the proportions of CD4+ lymphocytes in the pleural cavity (PLY)
      of patients with resectable non-small cell lung cancer. METHODS: Lymphocytes in
      the pleural cavity separated from 51 patients with non-small cell lung cancer
      were examined by flow cytometry to measure the proportions of CD4+ PLY.
      Univariate and multivariate analyses were performed to assess the association
      between the proportion of CD4+ PLY and survival. RESULTS: The 5 year survival
      rate of patients with percentage CD4+ PLY of < or = 30% was 84% whereas that of
      patients with %CD4+ PLY > 30% was 26.9%. The difference in survival between the
      %CD4+ PLY < or = 30% and %CD4+ PLY > 30% groups was significant (p < 0.0001). The
      %CD4+ PLY in those who survived for 5 years was significantly lower than that in
      the patients who died within 5 years (p < 0.0001). The difference in survival
      between patients with stage IA and IB lung cancer with %CD4+ PLY < or = 30% and
      those with %CD4+ PLY > 30% was also significant (p = 0.015). Multivariate
      analysis showed that the proportion of CD4+ PLY (hazard ratio = 6.9, 95% CI 0.045
      to 0.47) and nodal status (hazard ratio = 22.7, 95% CI 0.006 to 1.806) are
      significant and independent prognostic factors for the survival of patients with
      lung cancer. CONCLUSIONS: The proportion of CD4+ PLY may help to select patients
      who are likely to have a poorer prognosis after surgery and therefore may be
      suitable for consideration of adjuvant treatments. These results need
      confirmation in a larger prospective study.

PMID- 11462068
TI  - Transforming growth factor beta2 induced pleurodesis is not inhibited by
      corticosteroids.
AB  - BACKGROUND: Talc and tetracyclines induce pleurodesis by directly injuring the
      pleura. The injury results in intense inflammation which subsequently leads to
      fibrosis. Corticosteroids can inhibit talc pleurodesis by reducing the
      inflammatory process. We hypothesised that transforming growth factor beta2
      (TGFbeta2), a fibrogenic cytokine with immunomodulatory functions, could induce
      effective pleurodesis without generating significant pleural inflammation and
      therefore remain effective despite co-administration of corticosteroids. METHODS:
      Thirty rabbits were divided into two groups. Rabbits in the steroid group
      received weekly intramuscular injections of triamcinolone diacetate (0.8 mg/kg).
      Ten rabbits in each group were given 5.0 microg TGFbeta2 intrapleurally via a
      chest tube while the remaining five received 1.7 microg TGFbeta2. Pleurodesis was
      graded macroscopically after 14 days from 1 (none) to 8 (>50% symphysis).
      RESULTS: TGFbeta2 produced excellent pleurodesis at both 5.0 microg and 1.7
      microg doses. The pleural effusions produced after the injection were low in all
      inflammatory markers. No significant differences were seen between the steroid
      group and controls in macroscopic pleurodesis scores (7.2 (1.3) v 7.1 (1.2)),
      levels of inflammatory markers in the pleural fluids (leucocyte 1107 (387)/mm(3)
      v 1376 (581)/mm(3); protein 3.1 (0.3) mg/dl v 2.9 (0.3) mg/dl, and LDH 478 (232)
      IU/l v 502 (123) IU/l), and the degree of microscopic pleural fibrosis and
      pleural inflammation. CONCLUSIONS: TGFbeta2 can induce effective pleurodesis and
      remains effective in the presence of high dose parenteral corticosteroids.

PMID- 11462069
TI  - Women with cystic fibrosis and their potential for reproduction.

PMID- 11462070
TI  - Interventions for smoking cessation in hospitalised patients: a systematic
      review.
AB  - BACKGROUND: An admission to hospital provides an opportunity to help people stop
      smoking. Individuals may be more open to help at a time of perceived
      vulnerability, and may find it easier to quit in an environment where smoking is
      restricted or prohibited. Providing smoking cessation services during
      hospitalisation may help more people to attempt and sustain an attempt to quit.
      The purpose of this paper is to systematically review the effectiveness of
      interventions for smoking cessation in hospitalised patients. METHODS: We
      searched the Cochrane Tobacco Addiction Group register, CINAHL, and the Smoking
      and Health database for studies of interventions for smoking cessation in
      hospitalised patients. Randomised and quasi-randomised trials of behavioural,
      pharmacological, or multi-component interventions to help patients stop smoking
      conducted with hospitalised patients who were current smokers or recent quitters
      were included. Studies of patients admitted for psychiatric disorders or
      substance abuse, those that did not report abstinence rates, and those with
      follow up of less than 6 months were excluded. Two of the authors extracted data
      independently for each paper, with assistance from others. RESULTS: Intensive
      intervention (inpatient contact plus follow up for at least 1 month) was
      associated with a significantly higher cessation rate compared with controls
      (Peto odds ratio (OR) 1.82, 95% CI 1.49 to 2.22). Any contact during
      hospitalisation followed by minimal follow up failed to detect a statistically
      significant effect on cessation rate, but did not rule out a 30% increase in
      smoking cessation (Peto OR 1.09, 95% CI 0.91 to 1.31). There was insufficient
      evidence to judge the effect of interventions delivered only during the hospital
      stay. Although the interventions increased quit rates irrespective of whether
      nicotine replacement therapy (NRT) was used, the results for NRT were compatible
      with other data indicating that it increases quit rates. There was no strong
      evidence that clinical diagnosis affected the likelihood of quitting.
      CONCLUSIONS: High intensity behavioural interventions that include at least 1
      month of follow up contact are effective in promoting smoking cessation in
      hospitalised patients.

PMID- 11462071
TI  - Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy.
AB  - Pulmonary alveolar proteinosis is a rare condition traditionally requiring
      treatment with whole lung lavage. The case is presented of a young man who
      obtained complete remission following treatment with granulocyte-macrophage
      colony stimulating factor, a new treatment option.

PMID- 11462072
TI  - Exercise in chronic pulmonary disease: limitations and rehabilitation.
AB  - Chronic pulmonary disease is common in the community and increasing in
      prevalence. Although numerous etiologies exist, chronic obstructive pulmonary
      disease secondary to tobacco smoking, and asthma constitute the majority of
      cases. The important impact of these diseases on patients is disabling
      breathlessness and impairment of functional exercise capacity. The symptoms set
      up a vicious cycle leading to physical deconditioning and worsening exercise
      performance. The discipline of pulmonary rehabilitation has been conclusively
      shown to reverse this process, resulting in improved functional capacity and
      reduced breathlessness. Pulmonary rehabilitation, therefore, should be viewed as
      essential secondary preventative care for the majority of patients with chronic
      pulmonary disease. As such, early disease recognition and implementation of
      exercise reconditioning is important. In order to be maximally effective,
      pulmonary rehabilitation must recognize the complex underlying pathophysiology in
      chronic pulmonary disease and be customized to the individual patient. The chosen
      mode of exercise training should recognize that in order to be truly beneficial,
      any physiological responses need to translate readily into improvements in
      activities of daily living. Therefore, sessions in pulmonary rehabilitation
      should concentrate on exercises that have proven useful in this regard. Aerobic
      and resistance exercise prescriptions should be rigorous, scientifically based,
      and derived from an understanding of the basic principles of the human response
      to exercise prescription. Each of these exercise prescriptions should encompass
      the basic principles of intensity, frequency, duration, and progression suitably
      modified for the individual patient with chronic pulmonary disease.

PMID- 11462073
TI  - Ventilatory limitations in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder
      characterized by dysfunction of the small and large airways, as well as by
      destruction of the lung parenchyma and vasculature, in highly variable
      combinations. Breathlessness and exercise intolerance are the most common
      symptoms in COPD and progress relentlessly as the disease advances. Exercise
      intolerance is multifactorial, but in more severe disease, ventilatory limitation
      is often the proximate exercise-limiting event. Multiple factors determine
      ventilatory limitation and include integrated abnormalities in ventilatory
      mechanics and ventilatory muscle function as well as increased ventilatory
      demands (as a result of gas exchange abnormalities) and alterations in the
      neuroregulatory control of breathing. Despite its heterogeneity, the
      pathophysiological hallmark of COPD is expiratory flow limitation. When
      ventilation increases in flow-limited patients during exercise, air trapping is
      inevitable and causes further dynamic lung hyperinflation (DH) above the already
      increased resting volumes. DH causes elastic and inspiratory threshold loading of
      inspiratory muscles already burdened with increased resistive work. It seriously
      constrains tidal volume expansion during exercise. DH compromises the ability of
      the inspiratory muscles to generate pressure, and the positive intrathoracic
      pressures likely contribute to cardiac impairment during exercise. Progressive DH
      hastens the development of critical ventilatory constraints that limit exercise
      and, by causing serious neuromechanical uncoupling, contributes importantly to
      the quality and intensity of breathlessness. The corollary of this is that
      therapeutic interventions that reduce operational lung volumes during exercise,
      by improving lung emptying or by reducing ventilatory demand (which delays the
      rate of DH), result in clinically meaningful improvement of exercise endurance
      and symptoms in disabled COPD patients.

PMID- 11462074
TI  - Cardiovascular limitations in chronic pulmonary disease.
AB  - Chronic lung disease has significant impact on cardiovascular function. Much of
      this effect is because of increased right ventricular afterload caused by
      increased pulmonary vascular resistance resulting from structural changes in the
      pulmonary circulation, and because of hypoxic pulmonary vasoconstriction. In the
      case of chronic obstructive diseases, there may be additional increases in
      afterload resulting from dynamic hyperinflation. These processes can lead to
      structural changes in the heart (cor pulmonale), including right ventricular
      dilatation and hypertrophy, to maintain right ventricular output. In most
      ambulatory patients with chronic obstructive disease, it appears that cardiac
      output may be maintained at levels that are similar to normal both at rest and
      during exercise, with no consistent improvement in maximal exercise function
      afforded by interventions that increase blood flow. In contrast, diseases
      characterized by fibrosis or infiltration of the lung parenchyma may be
      associated with a disproportionate increase in pulmonary vascular resistance and
      more pronounced cardiovascular impairment, particularly with exercise.

PMID- 11462075
TI  - Skeletal muscle dysfunction in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a major health care problem.
      Formerly mainly a disease of men, women are increasingly frequently afflicted. In
      many of these patients, exercise intolerance is the chief complaint. Few
      effective therapies are available. In recent years, dysfunction of the muscles of
      ambulation has been identified as a source of a portion of the exercise
      intolerance these patients experience, and this dysfunction has been shown to be,
      at least in part, remediable. Mechanisms inducing muscle dysfunction include
      disuse atrophy, malnutrition, low levels of anabolic steroids, and myopathy from
      corticosteroid use. Endurance exercise training has been conclusively
      demonstrated to improve exercise tolerance in COPD. Recent studies suggest that
      strength training is beneficial as well. A new frontier of therapy for muscle
      dysfunction in COPD is the use of anabolic hormones. Testosterone supplementation
      has been shown to increase muscle mass and strength in both hypogonadal and
      eugonadal healthy men. Low-dose testosterone supplementation is being considered
      for use in postmenopausal women. Though short-term administration of testosterone
      in moderate doses seems to be well tolerated in both men and women, further
      studies are required before safety and effectiveness can be established for
      routine use in COPD patients.

PMID- 11462076
TI  - Exercise in chronic pulmonary disease: aerobic exercise prescription.
AB  - Endurance exercise training (EXT) is singly the most important aspect of
      rehabilitation for patients with chronic pulmonary disease. When effective, this
      modality of physical reconditioning leads to improved functional exercise
      capacity and reduced breathlessness. Early implementation is desirable to obtain
      more meaningful responses (e.g., when FEV1 falls below 50% of the predicted value
      in patients with chronic obstructive disease). Preparation for effective EXT
      requires optimization of respiratory system mechanics (e.g., using bronchodilator
      therapy), prevention of gas exchange failure (i.e., using supplemental oxygen),
      nutritional guidance, and psychological support (e.g., to overcome stigmata of
      disability, fear, and inclination to panic). EXT should be applied using a
      rigorous, scientifically based aerobic exercise prescription (AXRx) that
      recognizes basic principles of the human response to exercise prescription while
      considering individual pathophysiological limitations and identifying safety
      thresholds for exercise participation. The mode of aerobic exercise should use
      large muscle groups of the legs (e.g., treadmill or cycle ergometer). The
      recommended duration is an accumulation of 30 min of exercise per session at the
      target intensity, achieved by continuous or interval training. EXT should be
      supervised with a recommended frequency of at least three times per week for 6--8
      wk. Target exercise intensity can be monitored by oxygen uptake, work rate, heart
      rate, or perceived exertion. Target intensity can be determined initially on the
      basis of 40% of a reference value for maximum oxygen uptake and linked to other
      variables through predictable interrelationships. All aspects of the AXRx must be
      reviewed with regard to progression during training. Pulmonary rehabilitation
      must recognize the importance of achieving clinically meaningful responses (e.g.,
      increased 6-min walking distance of 54 m) as well as the need for maintenance
      exercise program to sustain the benefits.

PMID- 11462077
TI  - Exercise in chronic pulmonary disease: resistance exercise prescription.
AB  - Resistance exercise training has received relatively little attention as a means
      to reduce the muscle dysfunction and ensuing exercise intolerance seen in chronic
      pulmonary diseases. To date, only a few studies have examined the characteristics
      of skeletal muscle function or its responsiveness to strength training in
      patients with chronic respiratory diseases. It is clear from these studies,
      however, that peripheral muscle, particularly muscles of ambulation, are weak in
      patients with lung disease, exhibiting effort-dependent strength scores that are
      70--80% of these measures in age-matched healthy subjects. The degree to which
      this dysfunction is accounted for by deconditioning, disease-related myopathy, or
      other causes is unclear. It is evident, however, that patients with chronic
      respiratory diseases can acquire and maintain substantial improvements in
      skeletal muscle function, physical function, and quality of life through
      participation in a well-structured program of resistance exercise training.
      Despite the positive, albeit limited, evidence that skeletal muscle dysfunction
      may be improved with resistance training, no clear guidelines are available for
      this purpose. This review discusses the skeletal muscle dysfunction that
      accompanies chronic respiratory disease and presents strategies for resistance
      exercise training that may be considered as part of pulmonary rehabilitation.
      These strategies are derived from the successful outcomes noted in studies using
      resistance training in patients with COPD as well as on extrapolations from
      extant guidelines used to develop strength, power, and endurance in healthy
      individuals.

PMID- 11462078
TI  - New technologies in spine: kyphoplasty and vertebroplasty for the treatment of
      painful osteoporotic compression fractures.
AB  - STUDY DESIGN: Literature review. OBJECTIVES: To describe new treatments for
      painful osteoporotic compression fractures in light of available scientific
      literature and clinical experience. SUMMARY OF BACKGROUND DATA: Painful vertebral
      osteoporotic compression fractures lead to significant morbidity and mortality.
      This relates to pulmonary dysfunction, eating disorders (nutritional deficits),
      pain, loss of independence, and mental status change (related to pain and
      medications). Medications to treat osteoporosis (primarily antiresorptive) do not
      effectively treat the pain or the fracture, and require over 1 year to reduce the
      degree of osteoporosis. Kyphoplasty and vertebroplasty are new techniques that
      help decrease the pain and improve function in fractured vertebrae. METHODS: This
      is a descriptive review of the background leading to vertebroplasty and
      kyphoplasty, a description of the techniques, a review of the literature, as well
      as current ongoing studies evaluating kyphoplasty. RESULTS: Both techniques have
      had a very high acceptance and use rate. There is 95% improvement in pain and
      significant improvement in function following treatment by either of these
      percutaneous techniques. Kyphoplasty improves height of the fractured vertebra,
      and improves kyphosis by over 50%, if performed within 3 months from the onset of
      the fracture (onset of pain). There is some height improvement, though not as
      marked, along with 95% clinical improvement, if the procedure is performed after
      3 months. Complications occur with both and relate to cement leakage in both, and
      cement emboli with vertebroplasty. CONCLUSION: Kyphoplasty and vertebroplasty are
      safe and effective, and have a useful role in the treatment of painful
      osteoporotic vertebral compression fractures that do not respond to conventional
      treatments. Kyphoplasty offers the additional advantage of realigning the spinal
      column and regaining height of the fractured vertebra, which may help decrease
      the pulmonary, GI, and early morbidity consequences related to these fractures.
      Both procedures are technically demanding.

PMID- 11462079
TI  - Mechanosensitive afferent units in the lumbar posterior longitudinal ligament.
AB  - STUDY DESIGN: The mechanosensitive afferent units in the lumbar posterior
      longitudinal ligament were investigated in an animal model using an
      electrophysiologic technique. OBJECTIVES: The objectives of this study were to
      identify the mechanosensitive receptive fields in the lumbar posterior
      longitudinal ligament and to investigate their distribution and characteristics.
      SUMMARY OF BACKGROUND DATA: The lumbar posterior longitudinal ligament has a
      nerve network originating from the sinuvertebral nerve. These fibers are thin,
      and most of their terminals are free nerve endings. Some immunohistochemical
      studies have indicated that they are immunoreactive to calcitonin gene-related
      peptide and/or substance P, suggesting a nociceptive function. Most of these
      studies investigated morphologic aspects, and there have been few studies
      employing electrophysiologic techniques to examine mechanosensitive units.
      METHODS: We used 13 adult cats. They were anesthetized and then laminectomy was
      performed. The L5 and L6 dorsal rootlets were draped over a recording electrode.
      To investigate the receptive fields in the posterior longitudinal ligament,
      afferent impulses were evoked by mechanical stimulation with a glass probe. When
      the receptive fields were located, they were stimulated electrically to obtain
      conduction velocity and were stimulated with a set of 17 nylon filaments to
      determine their mechanical thresholds. RESULTS: Thirteen units were identified in
      the lumbar posterior longitudinal ligament. The majority of the units were
      located around the intervertebral disc level of the posterior longitudinal
      ligament. The mean mechanical threshold was 47.04 +/- 15.25 g. According to the
      conduction velocities of the units, 12 units were classified into Group III (0.5
      2.5 m/sec) and one unit into Group IV (2.5-20 m/sec). CONCLUSION:
      Mechanosensitive units classified into Group III or Group IV and with a high
      mechanical threshold (>7.0 g) were thought to act as nociceptive units. All units
      identified in this study satisfied these criteria. Our result suggests that
      afferent fibers from the lumbar posterior longitudinal ligament have a
      principally nociceptive function.

PMID- 11462080
TI  - Influence of macrophage infiltration of herniated disc tissue on the production
      of matrix metalloproteinases leading to disc resorption.
AB  - STUDY DESIGN: Herniated lumbar disc specimens were cocultured with peripheral
      blood mononuclear cells, and cells isolated from extruded disc were cultured to
      study the production of matrix metalloproteinases. OBJECTIVE: To investigate the
      role of peripheral blood mononuclear cells infiltrating extruded discs and disc
      derived cells in the production of matrix metalloproteinases. SUMMARY OF
      BACKGROUND DATA: Magnetic resonance imaging analysis of herniated disc patients
      revealed a progressive decrease in the size of herniated discs. Spontaneous
      regression of herniated disc is associated with infiltrating macrophages, and
      matrix metalloproteinases have been implicated in this phenomenon. However, the
      correlation between infiltrating macrophages and the production of matrix
      metalloproteinases has received little research attention. METHODS: Each disc
      specimen was incubated with homologous peripheral blood mononuclear cells. The
      numbers of peripheral blood mononuclear cells attached to the surfaces of
      herniated discs were counted and the culture media was assayed for MMP-3. The
      cells isolated from herniated discs were incubated with cytokines and the
      production of matrix metalloproteinases was measured. Total RNA was extracted
      from herniated discs and RT-PCR was carried out. RESULTS: Significantly larger
      numbers of peripheral blood mononuclear cells were attached to the surfaces of
      extruded discs, and higher amounts of MMP-3 were detected than those of control
      discs. The culture medium of extruded discs showed higher MMP-1 and MMP-3
      production than those from controls. Significant enhancement of MMP-1 and MMP-3
      mRNA expression was observed in the disc-derived cells stimulated with cytokines.
      CONCLUSION: These results suggest that peripheral blood mononuclear cells
      infiltrating extruded discs may secrete a variety of biologic materials capable
      of further recruiting monocytes into herniated discs in an autocrine fashion.
      Disc cells stimulated with cytokines showed enhanced production of matrix
      metalloproteinases, which might play an important role in spontaneous regression
      of disc materials.

PMID- 11462081
TI  - Stimulation of chemosensitive afferents from multifidus muscle does not sensitize
      multifidus muscle spindles to vertebral loads in the lumbar spine of the cat.
AB  - STUDY DESIGN: Electrophysiologic recordings from muscle spindle afferents
      innervating the lumbar multifidus muscle of the cat while loading the L6 vertebra
      at its spinous process and while exposing the segmentally adjacent lumbar
      multifidus muscles to algesic and inflammatory mediators. OBJECTIVES: The purpose
      of this study was to investigate a possible mechanism underlying muscle spasm and
      pain in the lumbar spine. The hypothesis was tested that stimulation of
      chemosensitive afferents with receptive endings in the paraspinal muscle
      increases the discharge of paraspinal muscle spindle afferents during loading of
      a lumbar vertebra. The presence of such a phenomenon would provide a mechanism by
      which pain or inflammation could alter segmental lumbar biomechanics and
      contribute to lumbar spine dysfunction. SUMMARY OF BACKGROUND DATA: Muscle pain,
      tenderness, and altered muscle tone are often associated with musculoskeletal
      disorders. The literature suggests that stimulation of Group III and IV muscle
      afferents sensitive to algesic or inflammatory metabolites increases the stretch
      sensitivity of muscle spindles via a reflex pathway involving gamma-motoneurons.
      The reflex increase in muscle spindle activity, in turn, reflexly increases the
      excitability of alpha-motoneurons leading to enhanced muscle tone and the further
      accumulation of muscle metabolites and subsequent pain. Studies in the cervical
      spine support this hypothesis. It has not been investigated in the lumbar spine.
      METHODS: Single unit activity from muscle spindles in the L6 multifidus muscle
      were recorded from the cut peripheral end of the L6 dorsal root in alpha
      chloralose-anesthetized cats and in decerebrate unanesthetized cats. The L6
      vertebra was loaded at its spinous process using a force-feedback motor. Ramp and
      hold loads were delivered at 25%, 50%, 75%, and 100% body weight. Chemosensitive
      afferents in the L5 and L7 multifidus muscle were stimulated by bathing
      (subfascial injection) or infiltrating (intramuscular injection) the L5 and L7
      multifidus muscles with bradykinin or capsaicin. RESULTS: Loading the L6 vertebra
      stimulated muscle spindles in the L6 multifidus muscle. Neither the saline volume
      control nor bradykinin nor capsaicin injected subfascially or intramuscularly
      affected the response of L6 multifidus muscle spindles to ramp and hold vertebral
      loads in the alpha-chloralose-anesthetized cat. In addition, neither saline nor
      bradykinin nor capsaicin injected intramuscularly affected the activity of L6
      multifidus muscle spindles to ramp and hold vertebral loads in the unanesthetized
      decerebrate cat. CONCLUSIONS: These results indicate that stimulation of small
      diameter muscle afferents in a deep muscle of the lumbar spine does not sensitize
      muscle spindles to vertebral loads. These data do not support the hypothesis that
      fusimotor reflexes evoked by chemosensitive muscle afferents contribute to muscle
      spasm or to changes in muscle tone in the lumbar spine. In addition, the present
      results do not provide evidence for the pain-spasm-pain cycle in the lumbar
      spine.

PMID- 11462082
TI  - The biomechanics of vertebroplasty. The effect of cement volume on mechanical
      behavior.
AB  - STUDY DESIGN: Ex vivo biomechanical study using osteoporotic cadaveric vertebral
      bodies. OBJECTIVE: To determine the association between the volume of cement
      injected during percutaneous vertebroplasty and the restoration of strength and
      stiffness in osteoporotic vertebral bodies, two investigational cements were
      studied: Orthocomp (Orthovita, Malvern, PA) and Simplex 20 (Simplex P with 20% by
      weight barium sulfate content; Stryker-Howmedica-Osteonics, Rutherford, NJ).
      SUMMARY OF BACKGROUND DATA: Previous biomechanical studies have shown that
      injections of 8-10 mL of cement during vertebroplasty restore or increase
      vertebral body strength and stiffness; however, the dose-response association
      between cement volume and restoration of strength and stiffness is unknown.
      METHODS: Compression fractures were experimentally created in 144 vertebral
      bodies (T6-L5) obtained from 12 osteoporotic spines harvested from female
      cadavers. After initial strength and stiffness were determined, the vertebral
      bodies were stabilized using bipedicular injections of cement totaling 2, 4, 6,
      or 8 mL and recompressed, after which post-treatment strength and stiffness were
      measured. Strength and stiffness were considered restored when post-treatment
      values were not significantly different from initial values. RESULTS: Strength
      was restored for all regions when 2 mL of either cement was injected. To restore
      stiffness with Orthocomp, the thoracic and thoracolumbar regions required 4 mL,
      but the lumbar region required 6 mL. To restore stiffness with Simplex 20, the
      thoracic and lumbar regions required 4 mL, but the thoracolumbar region required
      8 mL. CONCLUSION: These data provide guidance on the cement volumes needed to
      restore biomechanical integrity to compressed osteoporotic vertebral bodies.

PMID- 11462083
TI  - An ex vivo biomechanical evaluation of a hydroxyapatite cement for use with
      vertebroplasty.
AB  - STUDY DESIGN: Comparative ex vivo biomechanical study. OBJECTIVE: To determine
      the strength and stiffness of osteoporotic vertebral bodies subjected to
      compression fractures and stabilized via bipedicular injections of the following:
      1) Simplex P (Stryker-Howmedica-Osteonics, Rutherford, NJ), 2) Simplex P
      formulated consistent with the practice of vertebroplasty (F2), or 3) BoneSource
      (Stryker-Howmedica-Osteonics). SUMMARY OF BACKGROUND DATA: Little is known about
      the mechanical stabilization afforded by new materials proposed for use with
      vertebroplasty. METHODS: Vertebral bodies (T8-T10 and L2-L4) from each of 10
      fresh spines were harvested from female cadavers (81 +/- 12 years), screened for
      bone density (t score, -3.8 +/- 1.1; bone mineral density, 0.75 +/- 15 g/cm2),
      disarticulated, and compressed to determine initial strength and stiffness. The
      fractured vertebral bodies were stabilized via bipedicular injections of 4 mL
      (thoracic) or 6 mL (lumbar) and then recrushed. RESULTS: Vertebral bodies
      repaired with Simplex P resulted in significantly greater strength (P < 0.05)
      relative to their prefracture states, those repaired with BoneSource resulted in
      the restoration of initial strength for both the thoracic and lumbar level, and
      those repaired with F2 resulted in significantly greater strength (P < 0.05) in
      the thoracic region and restoration of strength in the lumbar region. All cement
      treatments resulted in significantly less stiffness compared with initial values.
      CONCLUSIONS: All three materials tested restored or increased vertebral body
      strength, but none restored stiffness. Both new materials show promise for use in
      percutaneous vertebroplasty, but they need clinical evaluation.

PMID- 11462084
TI  - Effects of bone cement volume and distribution on vertebral stiffness after
      vertebroplasty.
AB  - STUDY DESIGN: The biomechanical behavior of a single lumbar vertebral body after
      various surgical treatments with acrylic vertebroplasty was parametrically
      studied using finite-element analysis. OBJECTIVES: To provide a theoretical
      framework for understanding and optimizing the biomechanics of vertebroplasty.
      Specifically, to investigate the effects of volume and distribution of bone
      cement on stiffness recovery of the vertebral body. SUMMARY OF BACKGROUND DATA:
      Vertebroplasty is a treatment that stabilizes a fractured vertebra by addition of
      bone cement. However, there is currently no information available on the optimal
      volume and distribution of the filler material in terms of stiffness recovery of
      the damaged vertebral body. METHODS: An experimentally calibrated, anatomically
      accurate finite-element model of an elderly L1 vertebral body was developed.
      Damage was simulated in each element based on empirical measurements in response
      to a uniform compressive load. After virtual vertebroplasty (bone cement filling
      range of 1-7 cm3) on the damaged model, the resulting compressive stiffness of
      the vertebral body was computed for various spatial distributions of the filling
      material and different loading conditions. RESULTS: Vertebral stiffness recovery
      after vertebroplasty was strongly influenced by the volume fraction of the
      implanted cement. Only a small amount of bone cement (14% fill or 3.5 cm3) was
      necessary to restore stiffness of the damaged vertebral body to the predamaged
      value. Use of a 30% fill increased stiffness by more than 50% compared with the
      predamaged value. Whereas the unipedicular distributions exhibited a comparative
      stiffness to the bipedicular or posterolateral cases, it showed a medial-lateral
      bending motion ("toggle") toward the untreated side when a uniform compressive
      pressure load was applied. CONCLUSION: Only a small amount of bone cement (
      approximately 15% volume fraction) is needed to restore stiffness to predamage
      levels, and greater filling can result in substantial increase in stiffness well
      beyond the intact level. Such overfilling also renders the system more sensitive
      to the placement of the cement because asymmetric distributions with large fills
      can promote single-sided load transfer and thus toggle. These results suggest
      that large fill volumes may not be the most biomechanically optimal
      configuration, and an improvement might be achieved by use of lower cement volume
      with symmetric placement.

PMID- 11462085
TI  - Osteoporosis changes the amount of vertebral trabecular bone at risk of fracture
      but not the vertebral load distribution.
AB  - STUDY DESIGN: A finite-element study to investigate the amount of trabecular bone
      at risk of fracture and the distribution of load between trabecular core and
      cortical shell, for healthy, osteopenic, and osteoporotic vertebrae. OBJECTIVES:
      To determine differences between healthy, osteopenic, and osteoporotic vertebrae
      with regard to the risk of fracture and the load distribution. SUMMARY OF
      BACKGROUND DATA: The literature contains no reports on the effects of osteopenia
      and osteoporosis on load distribution in vertebral bodies, nor any reports on the
      amount of trabecular bone at risk of fracture. METHODS: Computed tomography data
      of vertebral bodies were used to construct patient-specific finite-element
      models. These models were then used in finite-element analyses to determine the
      physiologic stresses and strains in the vertebrae. RESULTS: For all three classes
      of vertebrae the contribution of the trabecular core to the total load transfer
      decreased from about 70% near the endplates to about 50% in the midtransverse
      region. The amount of trabecular bone that is at risk of fracture was about 1%
      for healthy vertebrae, about 3% for osteopenic vertebrae, and about 16% for
      osteoporotic vertebrae. CONCLUSIONS: Our finite-element models indicated that
      neither osteopenia nor osteoporosis had any effect on the contribution of the
      trabecular core to the total load placed on the vertebra. The trabecular core
      carried about half the load. Our finite-element models indicated that
      osteoporosis had a significant effect on the amount of trabecular bone at risk of
      fracture, which increased from about 1% in healthy vertebrae to about 16% for
      osteoporotic vertebrae.

PMID- 11462087
TI  - Biomechanical and morphologic evaluation of a three-dimensional fabric sheep
      artificial intervertebral disc: in vitro and in vivo analysis.
AB  - STUDY DESIGN: We have developed a new artificial intervertebral disc consisting
      of triaxial three-dimensional fabric for the sheep lumbar spine. To clarify the
      characteristics of the new implant, a series of biomechanical tests and
      morphologic evaluations were conducted. OBJECTIVES: To investigate the static,
      viscoelastic, and fatigue properties of the three-dimensional fabric disc in
      comparison with natural sheep disc and to evaluate their biomechanical and
      morphologic alteration in vivo. SUMMARY OF BACKGROUND DATA: In its human
      dimensions the three-dimensional fabric disc revealed mechanical properties
      similar to a natural human disc. METHODS: The disc-body units from sheep spine
      and the sheep three-dimensional fabric discs underwent tensile-compressive (200
      N), torsional (5 Nm), and creep-recovery tests (30 minutes-30 minutes, 200 N).
      After fatigue loading (2 million, compressive 200 N) the biomechanical changes
      and the debris were investigated. For in vivo evaluation after placing in the
      sheep psoas muscles for 6 months, the surface of the three-dimensional fabric
      disc was evaluated using macroscopy and scanning electron microscopy, followed by
      previous biomechanical tests. RESULTS: The behavior of the sheep three
      dimensional fabric disc was similar to that of natural sheep disc in tensile
      compressive and creep-recovery tests. In torsional testing the behavior of
      natural sheep disc was more rigid than that of the sheep three-dimensional fabric
      disc. After fatigue loading there was no biomechanical change and no debris
      detected. Six months after surgery no morphologic deterioration was observed nor
      were there changes in biomechanical parameters. CONCLUSIONS: The sheep three
      dimensional fabric disc exhibited biomechanical and morphologic biostability,
      appropriate viscoelasticity, and excellent fatigue properties. The three
      dimensional fabric disc has a potential for clinical application of human
      intervertebral disc replacement.

PMID- 11462088
TI  - Hematogenous pyogenic facet joint infection.
AB  - STUDY DESIGN: Retrospective. OBJECTIVES: To determine the incidence, clinical
      presentation, diagnostic laboratory values, imaging characteristics, and optimal
      treatment of hematogenous pyogenic facet joint infections. SUMMARY OF BACKGROUND
      DATA: There are 27 documented cases of hematogenous pyogenic facet joint
      infections. Data regarding incidence, clinical presentation, diagnosis, and
      treatment response are incomplete because of the paucity of reported cases.
      METHODS: This is a retrospective study of all cases of hematogenous pyogenic
      facet joint infection treated at one institution. Data from previous publications
      were combined with the present series to identify pertinent clinical
      characteristics and response to treatment. RESULTS: A total of six cases (4%) of
      hematogenous pyogenic facet joint infection were identified of 140 cases of
      hematogenous pyogenic spinal infection at our institution. Combining all reported
      cases reveals the following: The average patient age is 55 years. Ninety-seven
      percent of cases occur in the lumbar spine. Epidural abscess formation
      complicates 25% of the cases of which 38% develop severe neurologic deficit.
      Erythrocyte sedimentation rate and C-reactive protein are elevated in all cases.
      Staphylococcus aureus is the most common infecting organism. Magnetic resonance
      imaging is accurate in identifying the septic joint and associated abscess
      formation. Percutaneous drainage of the involved joint has a higher rate of
      success (85%) than treatment with antibiotics alone (71%), but the difference is
      not significant (P = 0.37). CONCLUSIONS: Hematogenous pyogenic facet joint
      infection is a rare but underdiagnosed clinical entity. Facet joint infections
      may be complicated by abscess formation in the epidural space or in the
      paraspinal muscles. Uncomplicated cases treated with percutaneous drainage and
      antibiotics may fare better than those treated with antibiotics alone. Cases
      complicated by an epidural abscess and severe neurologic deficit should undergo
      immediate decompressive laminectomy.

PMID- 11462089
TI  - Efficacy and safety of ethanol injections in 18 cases of vertebral hemangioma: a
      mean follow-up of 2 years.
AB  - STUDY DESIGN: The clinical records and radiographs of 18 patients with vertebral
      hemangiomas treated with ethanol vertebroplasty were reviewed to evaluate the
      usefulness of this method. OBJECTIVES: To assess, after a mean 2-year follow-up,
      the complication rate, results, and patient satisfaction with ethanol injection
      into vertebral hemangioma. SUMMARY OF BACKGROUND DATA: There is controversy about
      the safety of ethanol injections in the treatment of vertebral hemangiomas.
      METHODS: Twenty-four patients with vertebral hemangiomas were prepared for
      ethanol vertebroplasty. Eighteen patients were treated with ethanol
      vertebroplasty (average age, 49 years; range, 18-77 years) with a mean follow-up
      of 2 years (range, 1-4 years). The rest of the patients were not treated with
      ethanol vertebroplasty because in a pretreatment test injection the contrast
      medium was not retained by the hemangioma. RESULTS: Intralesional injections of
      alcohol did not cause clinical complications in any of the cases. CONCLUSIONS:
      This study shows that intralesional alcohol injections can be considered a safe
      technique for vertebral hemangiomas. However, a careful technique is required.

PMID- 11462091
TI  - Estimation of spinal deformity in scoliosis from torso surface cross sections.
AB  - STUDY DESIGN: Correlation of torso scan and three-dimensional radiographic data
      in 65 scans of 40 subjects. OBJECTIVES: To assess whether full-torso surface
      laser scan images can be effectively used to estimate spinal deformity with the
      aid of an artificial neural network. SUMMARY OF BACKGROUND DATA: Quantification
      of torso surface asymmetry may aid diagnosis and monitoring of scoliosis and
      thereby minimize the use of radiographs. Artificial neural networks are computing
      tools designed to relate input and output data when the form of the relation is
      unknown. METHODS: A three-dimensional torso scan taken concurrently with a pair
      of radiographs was used to generate an integrated three-dimensional model of the
      spine and torso surface. Sixty-five scan-radiograph pairs were generated during
      18 months in 40 patients (Cobb angles 0-58 degrees ): 34 patients with adolescent
      idiopathic scoliosis and six with juvenile scoliosis. Sixteen (25%) were randomly
      selected for testing and the remainder (n = 49) used to train the artificial
      neural network. Contours were cut through the torso model at each vertebral
      level, and the line joining the centroids of area of the torso contours was
      generated. Lateral deviations and angles of curvature of this line, and the
      relative rotations of the principal axes of each contour were computed.
      Artificial neural network estimations of maximal computer Cobb angle were made.
      RESULTS: Torso-spine correlations were generally weak (r < 0.5), although the
      range of torso rotation related moderately well to the maximal Cobb angle (r =
      0.64). Deformity of the torso centroid line was minimal despite significant
      spinal deformity in the patients studied. Despite these limitations and the small
      data set, the artificial neural network estimated the maximal Cobb angle within 6
      degrees in 63% of the test data set and was able to distinguish a Cobb angle
      greater than 30 degrees with a sensitivity of 1.0 and specificity of 0.75.
      CONCLUSIONS: Neural-network analysis of full-torso scan imaging shows promise to
      accurately estimate scoliotic spinal deformity in a variety of patients.

PMID- 11462093
TI  - Relationships between outcomes of conservative treatment and magnetic resonance
      imaging findings in patients with mild cervical myelopathy caused by soft disc
      herniations.
AB  - STUDY DESIGN: A retrospective follow-up study of conservatively treated patients
      with mild cervical myelopathy caused by cervical soft disc herniation. OBJECTIVE:
      To investigate the outcome of conservative treatment for patients with mild
      myelopathy caused by cervical soft disc herniation and to evaluate usefulness of
      magnetic resonance findings in the prediction of the outcomes. SUMMARY OF
      BACKGROUND DATA: Recent studies on conservative treatment for cervical soft disc
      herniation have focused mainly on radiculopathy, and not on myelopathy. METHODS:
      Twenty-seven patients with mild cervical myelopathy secondary to cervical soft
      disc herniation were treated conservatively for more than 6 months by cervical
      bracing and restriction of daily activities. Of the 27 patients, 17 patients
      (Group A) underwent conservative treatment only and it was associated with
      improvement in their neurologic deficits, while the other 10 patients (Group B)
      ultimately underwent decompression surgery because of neurologic deterioration.
      Comparisons between the two groups were made in regard to JOA scores, patient
      satisfaction, and magnetic resonance findings, including location of the disc
      herniation (focal or diffuse in the sagittal plane, median or paramedian in the
      axial plane). RESULTS: The JOA scores were 13.6 +/- 1.6 in Group A and 14.1 +/-
      1.6 in Group B before treatment, 14.9 +/- 1.0 and 12.9 +/- 2.1, respectively, at
      3 months, and 16.2 +/- 0.8 and 16.0 +/- 1.2, respectively, at the final follow
      up. The JOA scores at 3 months were significantly lower in Group B than in Group
      A. Satisfaction with the results of treatment at the final follow-up was reported
      by 77% of the patients in Group A and 90% in Group B. Focal-type herniation was
      present in 47% of the patients in Group A and 70% in Group B, while median-type
      herniation was diagnosed in 77% in Group A and 30% in Group B. Follow-up magnetic
      resonance imaging of the patients in Group A showed spontaneous regression of a
      herniated mass in 10 patients (59%). Diffuse-type herniations were more likely to
      regress spontaneously than focal-type herniations (78% vs. 37%). CONCLUSIONS:
      Conservative treatment is an effective treatment option for mild cervical
      myelopathy caused by cervical soft disc herniation. A good outcome can be
      expected in patients with a median-type and/or diffuse-type herniation on
      magnetic resonance imaging.

PMID- 11462094
TI  - Postoperative magnetic resonance imaging of lumbar disc herniation: comparison of
      microendoscopic discectomy and Love's method.
AB  - STUDY DESIGN: We performed a study to compare the magnetic resonance imaging
      findings up to 24 weeks after microendoscopic discectomy or surgery using Love's
      method in patients with lumbar disc herniation. OBJECTIVES: The objective was to
      determine whether or not microendoscopic discectomy was minimally invasive with
      respect to the nerve roots, cauda equina, and paravertebral muscles by comparing
      the postoperative magnetic resonance imaging findings in patients treated by
      microendoscopic discectomy and the conventional Love's method. SUMMARY OF
      BACKGROUND DATA: We introduced microendoscopic discectomy as a minimally invasive
      surgical procedure for lumbar disc herniation in September 1998 and have obtained
      good results. Microendoscopic discectomy is superior to the conventional Love's
      method in that it reduces postoperative pain, shortens the duration of
      hospitalization, and allows earlier resumption of normal activities. However, the
      effect of microendoscopic discectomy on the nerves and paravertebral muscles has
      not been evaluated objectively. METHODS: Enhancement of the nerve roots and
      paravertebral muscles, as well as the configuration of the cauda equina at the
      level of herniation, was assessed on axial magnetic resonance images obtained
      with contrast enhancement using gadolinium-diethylenetriamine penta-acetic acid
      before surgery and 1, 4, 8, 12, and 24 weeks after surgery in 25 patients who
      underwent microendoscopic discectomy and 15 patients who were treated using
      Love's method. RESULTS: Increased enhancement of the nerve roots was seen in
      50.0% of the microendoscopic discectomy group and 46.2% of the Love group at 1
      week after surgery. Enhancement of the paravertebral muscles at the surgical site
      tended to persist for longer in the microendoscopic discectomy group than in the
      Love group. However, muscle enhancement was widespread in some patients from the
      Love group. Abnormalities of the cauda equina attributed to surgical invasion
      were seen in 12.5% of the microscopic discectomy group and 15.4% of the Love
      group at 1 week after surgery. CONCLUSIONS: Microendoscopic discectomy had an
      effect on the nerve roots and cauda equina that was comparable with that of
      Love's method. The magnetic resonance images of the route of entry failed to show
      that microendoscopic discectomy is appreciably less invasive with respect to the
      paravertebral muscles.

PMID- 11462095
TI  - Back problems among postmenopausal women taking estrogen replacement therapy: the
      study of osteoporotic fractures.
AB  - STUDY DESIGN: Cross-sectional and prospective. OBJECTIVES: To investigate the
      association between estrogen replacement therapy use, back pain, and back
      function in a large cohort of elderly women. BACKGROUND: Several studies have
      suggested that women who use estrogen replacement therapy may be more likely to
      experience back pain than those who do not. However, the relationships between
      estrogen replacement therapy, back pain, and impaired back function have not been
      clearly delineated. METHODS: At baseline information on estrogen replacement
      therapy use, functional status, back pain and function, and general lifestyle
      variables was obtained from 7209 elderly white women (mean age 71 years)enrolled
      in the Study of Osteoporotic Fractures. Lateral radiographs of the lumbar and
      thoracic spine were taken at baseline and at the third clinic visit, an average
      of 3.7 years after the baseline visit. Bone mineral density at the hip and spine
      was measured approximately 2 years after baseline. Follow-up information on back
      pain and function was also obtained at the third clinic visit. RESULTS: A total
      of 1039 (14.4%) women were using estrogen replacement therapy at baseline,
      2016(28.0%) reported former use, and 4154 (57.6%) had never used estrogen
      replacement therapy. Compared with never-users, a statistically significant
      higher percentage of current estrogen users reported clinical back pain (52.7%
      vs. 43.4%) and back impairment (12.3% vs. 9.2%) at baseline and at the follow-up
      visit (pain 50.8% vs. 41%; impairment 16.0% vs. 12.1%). This occurred despite a
      higher prevalence of vertebral fractures in never-users of estrogen at the
      baseline visit. Current and former estrogen users without vertebral fractures had
      statistically significant higher likelihoods of having back pain and back
      dysfunction at both the baseline and third follow-up visit. The increased
      likelihood of back pain and back impairment in current and former estrogen users
      remained despite statistical adjustment for age, vertebral fracture, body mass
      index,smoking history, parity, exercise, arthritis, and diabetes in multivariate
      models. The relative risk (95%confidence interval) for impaired back function in
      former and current users at follow-up was 1.1 (0.9, 1.3) and 1.6 (1.3, 2.0),
      respectively. CONCLUSIONS: Our results indicate that postmenopausal estrogen use
      is associated with an increased likelihood of back pain and impaired back
      function in elderly white women.

PMID- 11462096
TI  - A comparison between bipedal and quadrupedal rats: do bipedal rats actually
      assume an upright posture?
AB  - STUDY DESIGN: A basic science animal investigation. OBJECTIVES: To determine if
      bipedal rats differ in upright posture compared with quadrupedal rats. SUMMARY OF
      BACKGROUND DATA: It has been reported that surgically induced bipedalism in the
      rat leads to habitual upright posture. Based on this finding, bipedal rats have
      been used to study the changes erect posture induces in bone, ligament, muscle,
      and intervertebral discs. Previous studies have used direct observation as a
      means to describe posture. This study is the first to quantify postural
      differences between bipedal and quadrupedal rats. METHODS: Eleven bipedal rats
      were created by forelimb and tail amputation within 24 hours of birth. Eleven
      quadrupedal rats served as controls. Specialized cages were used with infrared
      sensors, and a computer program measured the total amount of time in the upright
      stance, the number of stands, and the amount of horizontal movement in the
      upright stance. Statistical comparisons were made between bipedal and quadrupedal
      rats hourly and over a 24-hour period of time. RESULTS: Quadrupedal rats assumed
      an upright posture for a significantly greater amount of time than bipedal rats
      when monitored over 24 hours (P = 0.016). Quadrupedal and bipedal rats did not
      differ in the number of stands (P = 0.63) or in the amount of horizontal movement
      in the upright stance (P = 0.34) over 24 hours. Similar results were obtained
      when comparing hourly intervals. CONCLUSION: This study quantifiably indicates
      that bipedal rats do not assume a more erect posture and spend no more time in an
      upright position compared with quadrupedal rats. The upright posture may not be
      the cause of some previously reported anatomic changes observed in the bipedal
      rat.

PMID- 11462097
TI  - Neuromuscular neutral zones associated with viscoelastic hysteresis during cyclic
      lumbar flexion.
AB  - STUDY DESIGN: The reflexive EMG from the L3-L4 to L5-L6 multifidus of the in vivo
      feline was recorded during application of single passive flexion-extension cycle
      of the lumbar spine. OBJECTIVE: To determine the effect of viscoelastic
      hysteresis associated with a single-cycle flexion-extension and of increasing
      cycle frequency on the initiation and cessation displacement and tension
      thresholds of reflexive EMG from the multifidus muscles. SUMMARY OF BACKGROUND
      DATA: It is known that reflexive EMG can be recorded from some paraspinal muscles
      as a result of mechanical stimulation of lumbar ligaments and other viscoelastic
      structures. It is also known that mechanical neutral zones exist in the spine,
      that viscoelastic hysteresis is associated with a stretch-release cycle, and that
      the rate of stretch and release has a profound impact on viscoelastic tissue
      responses. It is unknown what are the neurologic neutral zones of the spine
      within which reflexive EMG does not exist, as well as the dependence of such
      neurologic neutral zones on viscoelastic hysteresis and increasing frequency of a
      flexion-extension cycle. METHODS: Single passive flexion-extension cycles of
      frequencies ranging from 0.1 to 1.0 Hz were applied to the lumbar spine of the
      feline while recording intramuscular EMG from the L3-L4 to L5-L6 multifidus. The
      displacement and tension thresholds associated with the initiation and cessation
      of EMG activity during the cycle were analyzed with respect to the cycles'
      viscoelastic hysteresis and frequency. The peak EMG discharge was tested for
      relationships with cycle frequency. RESULTS: The displacement and tension
      thresholds during the flexion phase of the cycle were significantly lower than
      the corresponding thresholds in the extension phase of the cycle. As the cycle
      frequency increased, EMG was triggered significantly earlier (lower displacement
      and tension thresholds) in the flexion phase and terminated earlier (higher
      displacement and tension thresholds) in the extension phase. The peak EMG was
      significantly larger as cycle frequency increased. CONCLUSIONS: Reflexive muscle
      forces are triggered at lower displacement or tension during flexion but diminish
      early during extension, leaving the spine unprotected for a substantial part of
      the extension movement. The muscle forces are recruited earlier and with larger
      intensity as the velocity of the movement increases, lending more protection to
      the spine. Faster extension movement, however, creates a larger window during
      which the spine is exposed to instability and injury because of lack of muscle
      forces.

PMID- 11462098
TI  - Is sacral instrumentation mandatory to address pelvic obliquity in neuromuscular
      thoracolumbar scoliosis due to myelomeningocele?
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To evaluate the functional outcome of
      two-stage anterior and posterior instrumented fusion without fixation to the
      sacrum on 11 patients with neuromuscular scoliosis from thoracolumbar
      myelomeningocele. SUMMARY OF BACKGROUND DATA: To our knowledge, there are no
      published results of combined anterior and posterior correction and fusion
      without inclusion of the sacrum in neuromuscular scoliosis from thoracolumbar
      myelomeningocele. In this article we present our experience and critically
      evaluate the functional outcome on 11 patients with neuromuscular scoliosis.
      PATIENTS AND METHODS: From July 1, 1992 through June 30, 1995, 11 consecutive
      patients with severe thoracolumbar scoliosis were admitted at our hospital. The
      mean age at operation was 12 years 9 months (range 9 years 9 months to 14 years 6
      months). All patients underwent a two-stage anterior and posterior spinal
      reconstruction. The patients were evaluated before surgery and after surgery.
      RESULTS: All patients were observed for a mean of 4 years 11 months (range 42-88
      months) from the time of second stage procedure. Before treatment the mean
      scoliosis was 81 degrees (range 55-110 degrees ); this was reduced to a mean of
      31 degrees (range 8-70 degrees ), and at the final follow-up the correction had
      deteriorated slightly to a mean of 35 degrees (range 12-80 degrees ). No patient
      had increased neurologic deficit or showed other major complication. CONCLUSIONS:
      Pelvic obliquity in thoracolumbar neuromuscular scoliosis from lumbosacral
      myelomeningocele spontaneously corrected when the scoliotic deformity is
      adequately addressed with instrumented fusion without inclusion of the sacrum.
      The correction obtained remained stable at follow-up. In the absence of a control
      group we believe that sparing lumbar segments from primary fusion offers these
      patients a better freedom of mobility.

PMID- 11462099
TI  - Prospective dynamic functional evaluation of gait and spinal balance following
      spinal fusion in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Prospective evaluation of gait and spinal-pelvic balance parameters
      in patients with adolescent idiopathic scoliosis undergoing a spinal fusion.
      OBJECTIVE: To evaluate changes in gait and three-dimensional alignment and
      balance of the spine relative to the pelvis as a consequence of spinal fusion.
      SUMMARY OF BACKGROUND DATA: Preoperative and postoperative spinal radiographs
      have been the major forms of outcome analysis of adolescent idiopathic scoliosis
      fusions. The use of optoelectronic analysis for posture and gait has gained
      acceptance recently. However, there is a paucity of data quantifying, comparing,
      and correlating structural and functional changes in patients undergoing
      scoliosis fusion surgery including upright posture and gait. METHODS: Thirty
      patients with adolescent idiopathic scoliosis undergoing an instrumented spinal
      fusion were prospectively evaluated. Coronal and sagittal vertical alignment was
      evaluated on radiographs (CVA-R, SVA-R), during upright posture (CVA-P and SVA
      P), and during gait (CVA-G, SVA-G). Transverse plane alignment was evaluated by
      the acromion-pelvis angle during gait. RESULTS: Gait speed was significantly
      decreased (P < 0.05) between preoperative (129 +/- 16 cm/sec) and 2-year
      postoperative (119 +/- 16 cm/sec) testing sessions. Decreasing gait speed was the
      result of significantly reduced cadence and decreased stride length. There were
      no significant differences for lower extremity kinematics over the entire gait
      cycle. Spinal-pelvic balance parameters showed significant improvement in mean
      CVA-R, CVA-G (P < 0.05), then unchanged CVA-P at 2 years postoperation. CVA-P was
      relatively unchanged while the mean CVA-G also showed significant improvement
      from preoperation (2.2 +/- 2.4 cm) to 2 years postoperation (1.3 +/- 1.3 cm)(P <
      0.05). The mean SVA-R, SVA-P, and SVA-G were unchanged at 2 years postoperation
      (P > 0.05). The acromion-pelvis angle during gait at maximum shoulder rotation
      was statistically improved at 1 year (P = 0.002) and 2 years (P = 0.001) after
      surgery. Importantly, CVA-P correlated with CVA-G, and SVA-P correlated with SVA
      G to the P < 0.05 level. CONCLUSIONS: Patients with adolescent idiopathic
      scoliosis undergoing spinal fusion show slightly decreased gait speed at 2 years
      postoperation without any change in lower extremity kinematics. Spinal-pelvic
      balance parameters are improved in the coronal plane and unchanged in the
      sagittal plane radiographically and during standing posture and gait. Transverse
      plane parameters also are improved at maximum shoulder rotation during gait.

PMID- 11462102
TI  - Editorial.

PMID- 11462103
TI  - From the Art Director's Desk.

PMID- 11462104
TI  - Pineal gland, melatonin and cancer. NEL Review.
AB  - Studies on the relationship between the pineal gland, melatonin and neoplastic
      disease have recently become one of the most fascinating aspects of pineal
      research. The first data suggesting a link between the pineal and cancer were
      published 70 years ago. However, the real progress in this area of research has
      been made in the last two decades. The bulk of the experimental evidence
      indicates the influence of the pineal gland on the malignant tumor formation
      and/or growth. The majority of reports point toward the oncostatic action of the
      pineal, exerted most probably by its hormone, melatonin, via different
      mechanisms, including modulation of endocrine and immune systems and direct
      antiproliferative action. The mechanisms of the oncostatic action of the pineal
      seem to be, however, very complex. There is some indication that the pineal gland
      may also play a role in human malignancy. Alterations in melatonin concentrations
      have been demonstrated in various tumor types including breast cancer, prostate
      cancer, colorectal carcinoma, and uterine cancer. Moreover, melatonin has been
      reported to be helpful in therapy of advanced cancer of various types. However,
      detailed 24h melatonin profiles must be studied in large numbers of patients with
      different types of tumors before determining whether melatonin concentrations
      have any diagnostic and/or prognostic values in cancer patients. Moreover, well
      designed clinical trials should be performed on the possible therapeutic
      significance of melatonin in neoplastic disease.

PMID- 11462105
TI  - Oxidative damage to nuclear DNA: amelioration by melatonin. NEL Review.
AB  - The indoleamine melatonin, a product of tryptophan metabolism in the pineal
      gland, is a free radical scavenger and antioxidant. This brief review summarizes
      melatonin's ability to protect nuclear DNA from oxidative damage. Using a variety
      of different cytogenetic, biochemical and molecular biological methods, a number
      of investigators have demonstrated melatonin's ability to protect DNA from the
      physical agent ionizing radiation, the herbicide paraquat, the carcinogen
      safrole, the excitotoxin kainic acid, the heavy metal chromium (VI), and a wide
      number of mutagens. Since these agents damage DNA because they generate free
      radicals, the observations are consistent with melatonin being a radical
      scavenger and antioxidant.

PMID- 11462106
TI  - Reciprocal interdependence between pineal gland and avian immune system. NEL
      Review.
AB  - The immune system of mammals and birds exhibits the same basic anatomical and
      functional organization, including dichotomy into the cellular and humoral immune
      response. Specificities of avian immune system may be, however, very useful for
      understanding numerous phylogenetic and evolutionary mysteries. Similarities and
      differences between mammals and birds in terms of several pineal gland functions
      are well known, and they seem to include the immunomodulatory activity of
      melatonin (MEL) as well. Embryonic pinealectomy of the chicken demonstrated
      functional interrelationships between the development of the pineal gland, immune
      system and/or neuroendocrine network, and embryonic bursectomy influenced the
      diurnal rhythm of the pineal gland function and abolished the effect of
      immunization on serum MEL level. Also immunization with a thymo-dependent antigen
      (SRBC) evoked some changes in the chicken nocturnal pineal NAT activity. We have
      found that the pineal gland and MEL control the diurnal rhythm of immunity in the
      chicken, but we were not able to demonstrate any immunostimulatory and anti
      glucocorticoid MEL effects, regardless of the chicken's age, sex, season, and
      hormone dose used. The existence of functional connections between the pineal
      gland and the immune system in chickens was, however, confirmed in other
      experimental approaches. Specific and reversible binding of 2-[125I]iodoMEL to
      the membrane preparations from lymphoid glands was demonstrated in several avian
      species. In vitro MEL diminished lymphocyte proliferation stimulated by the
      common T-cell mitogens, while alone failed to influence the blast formation.
      Reciprocal functional connections between the avian immune system and the pineal
      gland seem to be well documented, but the mechanism(s) involved have to be
      elucidated.

PMID- 11462107
TI  - Effects of melatonin on the oxidative stress induced by thyrotoxicosis in rats.
AB  - High concentrations of thyroid hormones can affect the metabolism of oxygen in
      aerobic conditions and stimulate free radicals generation in mitochondria.
      Reactive oxygen species are toxic to biomembranes and lead to peroxidation of
      lipids unless they are not removed by free radical scavengers. A few years ago
      melatonin (MEL), a pineal hormone, was described as a scavenger of free radicals,
      especially of hydroxyl and peroxyl radicals. The goal of the study was to examine
      the parameters of oxidative stress [the levels of conjugated dienes (CD),
      malondialdehyde (MDA) and Schiff bases (SB)] in male rats with thyrotoxicosis,
      induced by the injection of L-thyroxine (L-T4) in a dose of 100 &mgr;g/kg B.W.
      After one week of treatment with L-T4, the animals received MEL in a dose 5 mg/kg
      B.W., i.p., daily, for 7 days. Diagnosis of thyrotoxicosis was confirmed, using
      hormonal assays. We observed the increased concentration of free T4 (fT4) and
      free T3 (fT3) after L-T4 injections. The concentration of fT3 was diminished
      after MEL in L-T4-injected animals. In the liver, we did not observe any changes
      in the content of both CD and MDA after L-T4 injections but the content of SB was
      higher after L-T4 injections when compared to the control group. In the liver,
      melatonin did not change any parameters of oxidative stress, either alone or
      after L-T4. The changes in the parameters of oxidative stress were better
      expressed in the kidney, compared to the liver. Melatonin decreased the
      concentration of CD and SB in the kidneys of a group of animals with
      thyrotoxicosis. Additionally, MEL decreased the basal concentrations of CD and
      SB, when compared to the control group.

PMID- 11462108
TI  - Guest Editorial.

PMID- 11462109
TI  - Effects of melatonin on 24-h rhythms of neuroendocrine and immune changes in
      Freund's adjuvant-induced arthritis.
AB  - Old rats had significantly lower values of the amplitude of pineal melatonin
      content at any time point studied. Complete Freund's adjuvant administration
      reduced the amplitude of melatonin rhythm. On day 18 of arthritis development,
      decreased pineal melatonin contents were also seen in young rats. On day 18, a
      global depressive effect of arthritis development on pineal melatonin content was
      found. However, prolactin levels increased in old as compared to young rats.
      Freund's adjuvant administration brought about changes in the secretory pattern
      of prolactin in young and old animals that are opposite to those described for
      melatonin. Cell proliferation as assessed by ornithine decarboxylase activity
      exhibited significant 24-h variations with maximal activity of the enzyme during
      daily hours, acrophases varying from 13:15 to 16:52 h (lymph nodes). The mesor
      and amplitude of ornithine decarboxylase activity were lowest in old rats.
      Melatonin (100 &mgr;g) augmented amplitude of daily rhythm in submaxillary lymph
      node ornithine decarboxylase activity significantly. These data indicate that
      melatonin and prolactin change differentially during arthritis development in
      young and old animals, perhaps indicating opposite effects in the induction and
      maintenance of adjuvant-arthritis. The changes are compatible with the values of
      ornithine descarboxylase activity.

PMID- 11462110
TI  - Melatonin secretion in patients with pineal region tumors-preliminary report.
AB  - Tumors of the pineal region, though not very common, are recently more often
      diagnosed due to the introduction of computer tomography and magnetic resonance
      examinations into neurosurgical practice. However many controversies about the
      treatment of them still exist. Some of them need aggressive treatment. The others
      are benign and asymptomatic. Thus it seems to be important to improve our
      diagnosis of mass lesion of the pineal region, especially before taking a
      decision for surgery. The purpose of this study was to find any significant
      changes in the circadian pattern of melatonin secretion in patients with pineal
      region tumors. Blood samples were collected preoperatively from 21 patients with
      diagnosed pineal region tumors. In 13 patients sampling was performed at 08:00,
      14:00, 20:00 and 02:00 h during a 24-hour period but in 8 former ones only at
      02:00 h at night. The samples were immediately centrifuged and the serum stored
      at -20 degrees C until analysis. The patients stayed in the darkened room from
      23:00 to 05:00 h. Plasma melatonin was measured by direct and specific
      radioimmunoassay. The following three groups of results were found: (1) eight
      patients showed normal melatonin secretion profiles, (2) six cases with lack of
      the night maximum plasma value, and (3) seven cases with nocturnal melatonin
      concentration higher than in the healthy population (>100pg/ml). We observed no
      correlation between melatonin secretion and histological type of tumor. In
      conclusion, we suggest that changes of melatonin secretion could indicate the
      pineal region pathology. However further studies with a larger group of patients,
      especially with tumors originating from the pineal gland (pinealocytoma,
      pinealoblastoma), are necessary.

PMID- 11462111
TI  - The effect of morphine on melatonin secretion in the domestic pig. In vivo and in
      vitro study.
AB  - Up till now the results of performed investigations suggest the involvement of
      opioids in the regulation of the pineal gland activity in mammals. On the other
      hand, they show the existence of large interspecies differences in the presence
      of opioid peptides in the pineal gland and in the effects of opiates on the
      melatonin secretion. The aim of the present work was to study the influence of
      morphine on the melatonin secretion in the domestic pig. Morphine (about 2.5
      mg/kg) was given intravenously to immature gilts during the day, during the night
      or during the night with turned on fluorescent illumination (intensity 500 lx at
      the level of the animal heads) and plasma melatonin level was measured. The
      effect of various concentrations of morphine on basal or norepinephrine
      stimulated melatonin secretion was also investigated using perfusion culture of
      pineal glands of immature female pigs. Morphine did not change plasma melatonin
      concentration in the domestic pig when administered in a single dose at the
      beginning of the light or the dark phase of the diurnal light-dark cycle.
      However, morphine administration at the beginning of the night resulted in
      significantly decreased the plasma melatonin level in animals exposed to light,
      with intensity 500 lx, which was insufficient to block nocturnal rise in plasma
      concentration of this pineal hormone in the untreated pigs. Morphine had also no
      effect on the level of basal and norepinephrine-stimulated melatonin secretion in
      vitro. The obtained results suggest that in immature pigs morphine does not
      influence directly the pineal activity, but may modulate the melatonin secretion
      indirectly, increasing the sensitivity of the system generating melatonin
      synthesis and secretion to the light.

PMID- 11462112
TI  - Melatonin in humans-where we are 40 years after its discovery.
AB  - Although the pineal gland was well known for more than 2000 years and has been
      documented since Galen (130-200 AD), for many centuries different theories
      concerning its function were presented. The organ was believed to be a sphincter
      (ancient Greeks), the point at which the soul preeminently controls the body
      (Descartes, 1596-1650), a rudimentary organ (up to the 19th century), and a gland
      having endocrine function. Endocrine function of the pineal was postulated
      already at the end of 19th century and the beginning of the 20th century with the
      notion of antigonadotropic pineal influence, and the functional cooperation
      between the pineal and hypothalamo-hypophysial axis, but no secretory substance
      responsible for the gland function was known. In 1958 Lerner and coworkers
      succeeded in isolating from bovine pineal glands the compound termed melatonin
      because of its blanching effect on melanophores. This discovery constituted the
      milestone for further pineal research. Since then the knowledge of the structure
      and function of the pineal gland has tremendously increased, especially during
      the last two decades. However, it should be stressed that many problems in pineal
      research still must be solved. In this paper, the recent knowledge on the role of
      melatonin in humans is briefly presented.

PMID- 11462114
TI  - An analysis of Peer Gynt (Art Behind Science).

PMID- 11462113
TI  - Induction of endothelial nitric oxide synthase in perivascular mast cells in rat
      neurohypophysis after ischemia.
AB  - An electron microscopic immunocytochemical study was performed in order to
      determine the expression pattern of endothelial nitric oxide synthase (eNOS) in
      rat neurohypophysis after ischemia. In basal conditions eNOS was found to be
      weakly expressed on the endothelial cells and on single activated
      neurohypophyseal mastocytes. After cerebral ischemia, the number of mast cells
      increased in the neurohypophysis. The eNOS immunolabelling of mast cells was
      strongly enhanced between 10 min and 3 h after ischemia and declined at 24 h
      after ischemia. eNOS labelling was also enhanced in endotethelial cells between
      30 min and 3 h after ischemia. Ultrastructurally, eNOS labelling was restricted
      to the granules of activated mast cells and the cytoplasm of endothelial cells.
      This study suggests that cerebral mastocytes are an important source of eNOS in
      neurohypophysis during ischemia and contribute to nitric oxide production in the
      perivascular space.

PMID- 11462115
TI  - Hormonal evaluation in schizophrenic patients treated with neuroleptics.
AB  - The aim of this study was to hormonally evaluate schizophrenic patients on long
      term treatment with neuroleptics. Twenty-eight patients (14 men and 14 women) on
      long-term therapy with different neuroleptics were investigated. Blood samples
      for prolactin (PRL), growth hormone (GH) and insulin-like growth factor I (IGF-I)
      were measured, as well as gonadotropins and testosterone in the males. In
      addition, clinical signs and symptoms of the neuroleptic side effects were
      evaluated. Seven out of 14 women had elevated PRL and five of the six fertile
      women in this group had menstrual disturbances. Twelve of the l4 men had normal
      PRL levels, whereas two had slightly elevated PRL without related symptoms. Four
      patients had low IGF-I levels, which in one case was combined with elevated PRL.
      We conclude that PRL levels in schizophrenic patients on long-term therapy with
      neuroleptics are elevated in about 50% of the women and in 10-20% of the men.
      Furthermore, irrespective of PRL levels or other hormonal disturbances, some
      patients on long-term neuroleptic therapy show low IGF-I levels, pointing at a
      possible interference with neuroleptics on the hypothalamic-pituitary regulation
      of GH-dependent IGF-I secretion.

PMID- 11462116
TI  - Psychoimmuno-neuroendocrinology: An integrative approach to modern philosophy in
      medicine and psychology.
AB  - The immune system is now seen to be closely integrated with other physiological
      circuits, such as the central nervous system (CNS) and the neuroendocrine system.
      There is also an increasing amount of evidence that this integrated circuit is
      bidirectional and both systems exert a reciprocal effect on each other. We have
      always stressed the interdisciplinary nature of the science where disciplines and
      sciences such as medicine, biochemistry, genetics, psychology, human ethology,
      etc. meet and undergo a process of "cross-fertilization." We also have stressed
      the indivisibility of the somatic and psychological processes in the indivisible
      continuum of human life from its very beginning and the inseparability of the
      development and functions of the central nervous system and the immunological and
      neuroendocrine processes. This transdisciplinary and integrative aspect of
      sciences and their entree in the twenty-first century is the true vision for our
      common efforts. Integration means also amalgamation, assimilation, blending,
      combining, incorporation, unification and harmony. This last mentioned, harmony,
      should be stressed and underlined specifically: a harmony between different views
      and approaches, between different methods and methodologies, different theories
      and practices. In order to undertake such a challenge, a new scientific theory
      and a common language is required, a language that would be understood across
      disciplines and would be able to assist in getting beyond semantic problems. The
      bridge between the immune system, neuroendocrinology and the rest of the central
      nervous system opens the gateway to more common understanding and acceptance
      across the disciplines. It is an umbrella for the endeavor that unites various
      scientific fields in their attempt to elucidate the processes of experience
      involved from the earliest stages of human life. This integration does cross over
      the different disciplines and diagnostic systems. It attaches theoretical and
      applied fields, basic research and clinical experience throughout the whole
      continuity of human life from conception and onwards. Integrated Psychoimmuno
      Neuroendocrinology represents a unique opportunity for the primary prevention of
      psychological, emotional and physical disorders.

PMID- 11462117
TI  - Mercury and nickel allergy: risk factors in fatigue and autoimmunity.
AB  - This study examined the presence of hypersensitivity to dental and environmental
      metals in patients with clinical disorders complicated with chronic fatigue
      syndrome. Three groups of patients were examined through medical history, dental
      examination, and by using a modified test of blast transformation for metals
      MELISA(R). The three groups consisted of the following: 22 patients with
      autoimmune thyroiditis with or without polyglandular autoimmune activation; 28
      fatigued patients free from endocrinopathy; and 22 fatigued professionals without
      evidence of autoimmunity. As controls, a population sample or 13 healthy subjects
      without any evidence of metal sensitivity was included. Healthy controls did not
      complain of marked fatigue and their laboratory tests did not show signs of
      autoimmunity and endocrinopathy. We have found that fatigue, regardless of the
      underlying disease, is primarily associated with hypersensitivity to inorganic
      mercury and nickel. The lymphocyte stimulation by other metals was similar in
      fatigued and control groups. To evaluate clinical relevance of positive in vitro
      findings, the replacement of amalgam with metal-free restorations was performed
      in some of the patients. At a six-month follow-up, patients reported considerably
      alleviated fatigue and disappearance of many symptoms previously encountered; in
      parallel, lymphocyte responses to metals decreased as well. We suggest that metal
      driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis)
      and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue
      syndrome, fibromyalgia, and other diseases of unknown etiology.

PMID- 11462118
TI  - Effect of melatonin on in vitro gonadotropins and prolactin release from
      pituitary LHRH stimulated, and median eminence and on ovarian response to hCG in
      middle-aged female rats.
AB  - The possible influence of exogenous melatonin upon the reproductive axis of
      middle-aged (15-19-month-old) female rats showing irregular estrous cycle length
      was analyzed. In vitro pituitary and median eminence (ME) luteinizing hormone
      (LH), follicle stimulating hormone (FSH) and prolactin release and responsiveness
      to luteinizing hormone releasing hormone (LHRH) were investigated in control
      (n=12) and melatonin (150 &mgr;g/100 g BW) treated (n=16) rats. In vitro ovarian
      steroidogenic activity and its response to hCG were also evaluated. Basal
      secretion, first incubation after one hour (I(1)), second incubation after 2
      hours (I(2)) and after two hours plus LHRH (10(-7)) (I(2+LHRH)) or hCG (20 UI)
      (I(2+hCG)) were studied. Melatonin administration to middle-aged rats showed a
      different effect upon in vitro LH release than upon FSH since only lower FSH
      secretion rates were found. In vivo melatonin administration reduced in vitro LH
      release after LHRH stimulation and this was impaired to pituitary LH content,
      indicating that in vivo melatonin administration alters the mechanism of LH
      release but does not affect the LH synthesis. Neither melatonin nor LHRH affected
      hemipituitary in vitro prolactin release. In vivo melatonin administration again
      showed a different effect upon LH release than upon FSH from ME, showing
      decreasing FSH secretion rates. Similarly, melatonin did not affect prolactin
      release or ME content. Melatonin reduced estradiol release from hCG stimulated
      ovaries of middle-aged rats. We concluded that melatonin may have a physiological
      role in middle-aged rats since decreased in vitro basal FSH release and blunted
      LH and estradiol increase after stimuli.

PMID- 11462119
TI  - New analogs of somatostatin: inhibiting effectively GH, glucagon and insulin
      levels.
AB  - The in vivo effects of three new analogs of somatostatin (ASS-51, ASS-52 and ASS
      53 analogs) on GH, insulin and glucagon were studied in WKY rats. The solid phase
      method was used for the synthesis of ASS. Octreotide and ASS were given iv. in a
      dose of 0.05 &mgr;g/kg per animal in a time-dependent manner. ASS-52 and ASS-53
      were longer acting and more potent somatostatin analogs when compared to
      octreotide in producing the inhibition of GH. ASS-51 was found to be the most
      potent and selective inhibitor of insulin and glucagon release. Our results show
      that the increased inhibitory effect and the higher selectivity of the new
      somatostatin analogs may result from the differences in their chemical structure.
      ASS-52 is most active in inhibiting GH release. The mechanism by which ASS-52
      inhibits preferentially GH release may involve the opioid system and the
      activation of GABA-ergic receptors. In studies in vitro ASS-52 inhibited GH
      release from pituitary cells" culture.

PMID- 11462121
TI  - Mentoring: promoting a legacy for the future.

PMID- 11462122
TI  - Disclosure of HIV diagnosis to children: when, where, why, and how.
AB  - Despite recent recommendations by the American Academy of Pediatrics that
      strongly encourage disclosure of human immunodeficiency virus (HIV) infection to
      school-age children, health care providers vary widely in their actual disclosure
      practices. Concrete guidelines for accomplishing disclosure are not currently
      available. Nondisclosure can result in a variety of problems, including anxiety,
      depression, phobias, and exclusion from peer support groups and medical camps.
      This article reviews the available literature on disclosure of HIV infection to
      children and describes the disclosure process used in a large, urban pediatric
      HIV clinic.

PMID- 11462123
TI  - Over-the-counter medication use in preschool children.
AB  - INTRODUCTION: The purpose of this study was to describe how parents'/caregivers'
      perceptions of illness severity, susceptibility to illness, trust in primary care
      providers, perceived barriers to seeking care, and perceived effectiveness of
      over-the-counter (OTC) medication affect their decisions about the type of health
      care to provide for preschool children. In addition, the impact of social factors
      on the decision to give OTC medications to preschool children and/or the decision
      about whether to call the primary care provider was examined. METHODS: A
      descriptive correlational study was used with a convenience sample of 52
      caregivers of preschool-aged children. The OTC Medication Questionnaire and
      Medicine Decisions Questionnaire were given during parental Head Start meetings.
      RESULTS: Significant correlations existed between the age of the caregiver,
      socioeconomic status, perceived effectiveness of OTC medications, and the giving
      of OTC medications. Significant correlations also existed between perceived
      severity of illness, perceived susceptibility to illness, and calling the primary
      care provider or nurse practitioner. DISCUSSION: Specific guidelines for
      appropriate use of OTC medications should be provided to parents. These
      guidelines should include which OTC medications have proved to be effective.
      Anticipatory guidance by primary care practitioners is essential to prepare
      families for illnesses and illness progression, teach them about the efficacy and
      safe use of OTC medications, and help them use the health care system
      effectively.

PMID- 11462124
TI  - A bi-state, metropolitan, school-based immunization campaign: lessons from the
      Kansas City experience.
AB  - INTRODUCTION: Through school-based immunization programs, large numbers of
      children can be vaccinated in a cost-effective manner. Information from
      successful programs can be valuable to communities, schools, or pediatric health
      care providers considering the implementation of a school-based immunization
      program. The purpose of this study was to identify factors considered key to the
      success of a large bi-state, metropolitan, multi-school district, school-based,
      hepatitis B immunization program. METHOD: Immunizations were offered to 14,865
      sixth-grade students in 16 school districts at 123 public and private school
      buildings. Personnel from 6 health departments and numerous volunteers
      administered the vaccines. Twenty-two semistructured interviews were conducted
      with a representative sample of program participants from schools, health
      departments, and the coordinating immunization coalition. A qualitative, grounded
      theory analysis was performed using data from the interviews. RESULTS: The
      following categories emerged and were considered important issues in the success
      of a school-based program: organization, time, obtaining consent, educational
      opportunity, school support, and student tracking. DISCUSSION: School-based
      immunization programs can be successful, but they require a coordinated effort
      with school support to meet the challenges of obtaining consent and tracking
      students.

PMID- 11462125
TI  - Parenting classes: from birth to 3 years.
AB  - Parenting is a topic of great interest for pediatric nurse practitioners, because
      clinical practice is fraught with parenting concerns and dilemmas. This article
      provides information about resources available to health care providers that may
      be used to assist parents in their parenting endeavors. In addition, the article
      offers the philosophical basis and reported research supporting interventions
      with parents in general, as well as with specific curricula.

PMID- 11462126
TI  - Type 2 diabetes in children and adolescents: an emerging disease.
AB  - The incidence of type 2 diabetes is increasing in the United States, and minority
      populations in particular seem to be affected. In the past, it was thought that
      type 2 diabetes occurred only in adults. However, an alarming epidemic has
      emerged, and children as young as 8 years of age are now being diagnosed with the
      disease. The purpose of this article is to present pediatric nurse practitioners
      with the most recent information about type 2 diabetes in children and
      adolescents, summarize current understanding about diagnosis, and outline
      treatment options.

PMID- 11462127
TI  - Adolescent mothers' beliefs about parenting and injury prevention: results of a
      focus group.
AB  - INTRODUCTION: A nonfatal injury occurs every 2 seconds in the United States, and
      approximately 30,000 children die each year from injury-related causes. The U.S.
      Department of Health identified the reduction of unintentional injuries as a
      major health goal. The current study reports on a focus group discussion
      conducted with adolescent mothers to examine their beliefs and practices
      regarding injury prevention. METHOD: Seventeen first-time adolescent mothers
      participated in the focus group. Participants responded to questions about
      important aspects of mothering, causes of injury, and strategies to prevent
      injuries. Responses were categorized. RESULTS: No mother spontaneously identified
      injury prevention as an important part of mothering. More than half of all
      participants believed that injuries are unpreventable. Further, mothers
      identified a limited number of strategies to prevent injury. None of the mothers
      reported having discussed injury prevention with their child's pediatrician.
      DISCUSSION: Implications for care are discussed, including the need to address
      issues of injury prevention during well-baby care, the potential benefits of home
      visits, and specific challenges in implementing The Injury Prevention Program
      with young mothers.

PMID- 11462128
TI  - Constipation in children.

PMID- 11462129
TI  - Prevnar (heptavalent pneumococcal conjugate vaccine): disease prevention in
      infants and children.

PMID- 11462130
TI  - Boy with a cough and vomiting.

PMID- 11462131
TI  - Patients' bill of rights: NAPNAP's role in this legislative debate.

PMID- 11462132
TI  - Starting from scratch: developing your own practice site.

PMID- 11462133
TI  - Regarding childhood obesity.

PMID- 11462134
TI  - Toluene mineralization and growth potential of Pseudomonas putida PaW164 under
      toluene-limiting conditions.
AB  - Toluene-induced cells of Pseudomonas putida PaW164 (pWWO-164) were monitored for
      growth potential, maintaining the TOL plasmid, and potential toluene
      mineralization activity in toluene-amended and nonamended soil. A follow-up study
      was done in a carbon-free mineral salts solution to obtain further information on
      physiological changes that occur during starvation. These studies showed that
      there was a larger decline in colony forming units (CFUs) recovered on a toluate-
      or benzoate-defined mineral salts medium than on a complex agar medium, a greater
      percent decrease of CFU than of potential mineralization activity, no decrease in
      direct counts, and no loss of the TOL plasmid during starvation. Toluene-induced
      cells also showed an increasing lag time and a decreasing potential for
      mineralization of (14)C-toluene with starvation. In contrast, the lag time for
      mineralization of glucose was longest at the onset of starvation and reached a
      minimum by 3 days; thereafter, the potential for glucose mineralization remained
      high.

PMID- 11462135
TI  - Influence of organic solvents on the growth of marine microalgae.
AB  - Ninety-six-hour toxicity tests of five organic solvents (methanol, ethanol,
      acetone, N,N-dimethylformamide [DMF], and dimethyl sulfoxide [DMSO]) on nine
      species of marine microalgae (Bacillariophyceae; Skeletonema costatum, and
      Chaetoceros calcitrans, Prasinophyceae; Tetraselmis tetrathele, Haptophyceae;
      Isochrysis galbana and Pavlova lutheri, Dinophyceae; Prorocentrum minimum,
      Raphidophyceae; Heterosigma akashiwo, Euglenophyceae; Eutreptiella sp.,
      Chlorophyceae; Dunaliella tertiolecta) were conducted. For D. tertiolecta, T.
      tetrathele, I. galbana, and P. lutheri, methanol was the least toxic solvent. For
      S. costatum, C. calcitrans and Eutreptiella sp., DMSO was the least toxic
      solvent. For Heterosigma akashiwo, DMF was the least toxic solvent. In general,
      solvent toxicity was ethanol > methanol or acetone > DMF > DMSO. In relation to
      sensitivity of the microalgae to solvents, D. tertiolecta and T. tetrathele were
      lower in sensitivity, and Eutreptiella sp. and H. akashiwo were higher in
      sensitivity than the other species. The no observed effect concentration (NOEC)
      of acetone, DMF, and DMSO were higher than for ethanol and methanol. Acetone,
      DMF, and DMSO were suitable for carrier solvents used in toxicity test of water
      insoluble chemicals. Excellent regression between logEC(50) and logNOEC was
      obtained (logNOEC = 1.09 x logEC(50) - 0.84, R(2) = 0.91). This equation
      indicated that higher toxicity was higher application factor (EC(50)/NOEC) than
      lower toxicity. All application factors were higher than 0.1.

PMID- 11462136
TI  - Toxic effects of wastewaters collected at upstream and downstream sites of a
      purification station in cultures of rainbow trout hepatocytes.
AB  - The toxic effects of wastewater samples, collected in December 1998, from
      upstream (U) and downstream (D) sites of the purification station of the town of
      Nice (South-East France on the coast of the Mediterranean Sea) were assessed
      undiluted and at various dilutions (75%, 50%, and 25% of collected water sample),
      on trout hepatocyte cultures treated for 48 or 72 h. Chemical contamination
      (PCBs, PAHs, Cd, Cu, Pb, and Zn) was also evaluated by chemical analysis. The
      water samples from the upstream site were more cytotoxic than those from the
      downstream site. The induction of CYP1A enzyme and metallothioneins (MTs) were
      selected as specific indicators of exposure to organic contaminants and metals,
      respectively. CYP1A-related EROD activity as well as protein expression were
      found to be greatly induced after 72 h exposure of the hepatocytes to the
      undiluted water samples (U(100%) and D(100%)), but CYP1A1 mRNA was significantly
      overexpressed only by samples from the upstream site. Maximal MT levels were
      reached after 48 h of treatment with the least concentrated water samples (U(25%)
      and D(25%)). Glutathione S-transferase (GST) activities were similarly increased
      under the same conditions. On the other hand, there was no significant
      glutathione peroxidase (GPx) activity response. Induction of apoptosis was
      analyzed by using as markers both the fragmentation of the nuclear DNA into
      oligonucleosomal-length fragments recognized as a "DNA ladder" and the activation
      of DEVD (Asp-Glu-Val-Asp)-dependent protease considered as the central mediator
      of programmed cell death. Significant DNA cleavage was only detectable after 72-h
      exposure to the most concentrated water samples from upstream sites (U(75%) and
      U(100%)). DEVD-dependent protease activities were significantly increased, mainly
      in cells exposed to U(75%) and D(25%) for 72 h. In addition, pollution-related
      DNA damage assessed by using the Comet assay was approximatively 1.5 times
      greater than that of the control level with the undiluted water samples U(100%)
      and D(100%), after 72-h and 48-h exposure, respectively. The present study shows
      that such a multibiomarker-based approach could provide complementary
      information, for aquatic pollution monitoring, about the early biochemical
      effects in cells exposed to complex chemical pollution and could be considered as
      early warning systems to aquatic pollution.

PMID- 11462137
TI  - DDT toxicity and critical body residue in the amphipod Leptocheirus plumulosus in
      exposures to spiked sediment.
AB  - The lethal and sublethal toxicity of dichlorodiphenyltrichloroethane (DDT) to the
      estuarine amphipod Leptocheirus plumulosus was determined using sediment spiked
      with (14)C-labeled compound. Juvenile amphipods were exposed to concentrations up
      to 9.9 nmol/g dry weight (3.5 microg/g). Acute effects on survival were
      determined in a 10-day experiment. Chronic effects on survival, growth, and
      reproduction were assessed in a 28-day experiment. The DDT in the sediments
      transformed to dichlorodiphenyldichloroethane (DDD),
      dichlorodiphenyldichloroethylene (DDE), and polar metabolites during the 14-day
      sediment storage prior to exposing the amphipods. The mixture of DDT and its
      breakdown products (tDDT) was comprised mostly of DDT at the beginning of the
      exposures. DDD was the prevalent compound at termination of the 28-day exposure.
      Complete mortality occurred at sediment concentrations of tDDT as low as 7 nmol/g
      (2.3 microg/g) in both acute and chronic experiments. Most of the mortality
      appeared to have occurred within the first 4 days of exposure. No sublethal
      reductions in growth or reproduction were observed in the 28-day experiment. In
      the 10-day experiment, where amphipods did not receive supplemental food, growth
      was significantly increased in DDT treatments where survival was not affected.
      The concentration of tDDT in amphipod tissues was determined at exposure
      termination. In the 10-day experiment, a mean body residue of 14 nmol/g wet
      weight was associated with significant mortality (30%). Lower critical body
      residues were observed in the 28-day experiment, where the median lethal tissue
      residue (LR(50)) was 7.6 (6.8--8.4, 95% confidence interval) nmol/g wet weight.
      Based on previous studies, the lethal critical body residue for L. plumulosus is
      similar to those determined for freshwater amphipods and substantially lower than
      those determined for cladocerans and polychaetes.

PMID- 11462138
TI  - Trophic barriers to fertilizer Cd bioaccumulation through the food chain: a case
      study using a plant--insect predator pathway.
AB  - The objective of this study was to assess the uptake and subsequent transfer of
      Cd and Zn from a soil amended with a single application (150 kg P ha(-1)) of
      triple super phosphate fertilizer to wheat plants, aphids, and a predator and
      biocontrol agent of aphids, lacewings. The fertilizer amended soil and wheat
      plants grown on this soil had elevated concentrations of Cd compared to the
      controls, but similar concentrations of Zn. Aphids feeding on wheat plants on the
      fertilized soil had between three and seven times the concentrations of Cd and Zn
      observed in aphids feeding on the control plants. However, the lacewings showed
      no significant accumulation of Cd or Zn, and no differences in larval performance
      were recorded. Changes in the availability of Cd and Zn in the soils and the
      transfer through the plant-insect pathway were monitored using isotope dilution,
      by labeling the soils with carrier-free (109)Cd and (65)Zn. Decreases in the
      specific activities for Cd in the plants and aphids were observed for the
      fertilized soils compared to the controls, suggesting an increase in bioavailable
      Cd. On the fertilized soils the Cd:Zn ratio of the phloem-feeding aphids (0.008)
      was significantly less than the host plants (0.025), indicating a reduced
      relative uptake of Cd and a possible barrier for Cd along the soil--plant-
      herbivorous insect pathway--reducing uptake by phloem feeders and subsequently
      their predators.

PMID- 11462139
TI  - Content of metals in compartments of ecosystem of a siberian pond.
AB  - During three field seasons (June--September) of 1997--99 contents of Na, K, Ca,
      Mg, Fe, Mn, Zn, Cu, Al, Cr, Ni, Cd, and Pb were determined in compartments of
      ecosystem (surrounding soils, bottom sediments, water, zoobenthos, macrophytes,
      and fish) of a fish and recreation pond situated at the edge of Krasnoyarsk City
      (Siberia, Russia). Contents of most parts of metals in soils, water, and
      macrophytes significantly correlated with each other. As concluded, their
      contents were determined by natural, general, geochemical peculiarities of the
      region. Heavy metals, contents of which were higher than federal upper limits of
      concentration, were revealed. In muscles of fish with different feeding spectra-
      crucian and perch--concentrations of some metals differed significantly;
      correlation graphs for metals also had different structures. Comparison of our
      data with those on diverse aquatic ecosystems of Siberia, Europe, North America,
      and China published in the last decade was carried out. It was concluded that a
      distribution of heavy metals in the compartments of an aquatic ecosystem
      presently have to be determined for each particular water body until general
      regularities are discovered.

PMID- 11462140
TI  - Effects of copper and cadmium exposure on functional responses of hemocytes in
      the clam, Tapes philippinarum.
AB  - The effects of Cu and Cd on functional responses of hemocytes in Tapes
      philippinarum, a Veneridae clam widespread in the lagoon of Venice, were
      evaluated. Bivalves were exposed for 7 days to various concentrations of CuCl(2)
      x 2H(2)O (0, 10, 60, and 110 microg/L) and CdCl(2) x H(2)O (0, 150, 300, and 450
      microg/L). Hemocytes were collected from exposed clams, and the effects of Cu and
      Cd on phagocytosis, Neutral Red retention capacity, superoxide dismutase, and
      cytochrome oxidase activities were investigated. Hemocytes from animals exposed
      to Cu showed a significant decrease in phagocytic activity, whereas no inhibition
      was observed in cells from Cd-exposed animals. Diffusion of Neutral Red into the
      cytosol, an index of lysosomal membrane alteration, was enhanced by high
      concentrations of both metals. Different results in biochemical parameters were
      observed. Exposure to 60 and 110 microg Cu/L caused a significant reduction in
      hemocyte superoxide dismutase activity, whereas no changes resulted after Cd
      exposure. Increased cytochrome oxidase activity was observed in hemocytes from
      mollusks exposed to 60 microg Cu/L and 300 microg Cd/L; no significant
      differences were found in cells from bivalves exposed to 110 microg Cu/L and 450
      microg Cd/L. These results suggest a relationship between heavy metal exposure
      and alterations in functional responses of hemocytes in T. philippinarum and
      indicate that the type of observed effects vary with the nature and concentration
      of heavy metals. Moreover, the data obtained in the analyzed clam support the
      possibility of using it as sentinel organism in biomonitoring studies, even if
      used biomarkers will be further evaluated in field conditions.

PMID- 11462141
TI  - Changes in selenium, copper, cadmium, and zinc concentrations in mullet (Mugil
      cephalus) from the southern basin of Lake Macquarie, Australia, in response to
      alteration of coal-fired power station fly ash handling procedures.
AB  - Selenium, copper, cadmium, and zinc concentrations were measured in mullet (Mugil
      cephalus) from the southern basin of Lake Macquarie, Australia, in 1997 to
      determine if improved ash-handling practices at an adjacent coal fired power
      station, implemented in 1995, had significantly lowered trace metal
      concentrations in mullet tissues. Mean muscle tissue concentrations of selenium
      (5.9 +/- 0.7 microg/g dry mass), copper (3.6 +/- 0.1 microg/g dry mass), and zinc
      (14 +/- 1 microg/g dry mass) are lower than previously reported for mullet
      analyzed in 1993 (10 +/- 2, 21 +/- 3, 27 +/- 3 microg/g dry mass, respectively).
      Cadmium concentrations in liver tissues increased from 2.3 +/- 0.3 to 6 +/- 2
      microg/g dry mass. Significant intra-tissue correlations between metal
      concentrations were found for all tissues except muscle. Strong correlations of
      selenium, copper, and zinc concentrations were found in liver tissues, indicating
      a common primary source may exist for these metals, such as fly ash. All trace
      metals were found to have significant inter-tissue correlations, with strong
      correlations occurring for selenium between all tissues and for cadmium between
      all tissues except muscle. Regulation of copper, cadmium, and zinc appears to be
      occurring in muscle tissue. Selenium concentrations in mullet are still above
      levels considered to be of concern to human consumers. Trace metal concentrations
      are below that known to effect the health of fish. Mullet are directly exposed to
      trace metal concentrations as a result of feeding and the ingestion of
      contaminated sediment and detritus. Lower metal concentrations found in mullet
      tissues are attributed to the burial of highly contaminated sediment with
      material containing lower trace metal concentrations. Little of the variations in
      trace metal concentrations between mullet was explained by mass, gender, or age.

PMID- 11462142
TI  - Plasma androgen correlation, EROD induction, reduced condition factor, and the
      occurrence of organochlorine pollutants in reproductively immature white sturgeon
      (Acipenser transmontanus) from the Columbia River, USA.
AB  - White sturgeon (Acipenser transmontanus) support an active fishery in the
      Columbia River, but there is poor reproductive success within the impounded
      sections. The poor reproductive success has been attributed to hydroelectric
      development; however, water pollution could be a significant factor. White
      sturgeon plasma, liver, and gonad samples were collected from four Columbia River
      locations and a California aquaculture facility. Total length and weight of the
      fish were measured, and plasma samples were analyzed for testosterone (T), 11
      ketotestosterone (KT), 17 beta-estradiol (E2), and vitellogenin. Liver samples
      were analyzed for chlorinated pesticides and polychlorinated biphenyls,
      ethoxyresorufin-O-deethylase (EROD) activity and histopathology. Gonads were
      examined histologically to assess sexual maturity and characterize any lesions.
      Significant differences by location existed for p,p'-DDE, EROD activity, and
      condition factor. Plasma T was negatively correlated with p,p'-DDE in males and
      females, and plasma KT was negatively correlated in males. These data indicate
      that pollutants could be adversely affecting white sturgeon in the Columbia River
      basin.

PMID- 11462143
TI  - Behavioral and olfactory responses to prochloraz, bentazone, and nicosulfuron
      contaminated flows in goldfish.
AB  - The immediate behavioral responses of goldfish (Carassius auratus) to pesticide
      contaminated flows were recorded in a countercurrent olfactometer. In addition,
      electro-olfactograms were recorded from the epithelial surface of the olfactory
      rosette as a preliminary check for the olfactory sensitivity of the fish to the
      pesticides tested. All tests were run on prochloraz (imidazole fungicide),
      bentazone (diazine herbicide), and nicosulfuron (sulfonylurea herbicide).
      Behavioral effects were assessed, at four concentrations (10 microg/L, 100
      microg/L, 1 mg/L, 10 mg/L), on endpoints related to swimming pattern (preference
      avoidance responses, burst swimming reactions), comfort activities (buccal
      movements, feeding attempts), and social relations (antagonistic acts, grouping).
      The behavior of the fish appeared particularly sensitive to prochloraz exposure.
      As a whole, prochloraz-contaminated flows showed significant effects on the six
      behaviors studied; bentazone and nicosulfuron affected three and five,
      respectively. At the lowest concentration, prochloraz also showed more effects
      than the two other pesticides. Some of the behavioral endpoints were found
      particularly sensitive to a given chemical. Pesticide-contaminated flows also
      induced significant changes in swimming orientation of the fish. Attraction was
      observed in response to flowing solutions of prochloraz (1 mg/L, 10 mg/L),
      bentazone (10 microg/L, 10 mg/L), and nicosulfuron (1 mg/L, 10 mg/L). At a
      concentration of 1 mg/L, none of the pesticides induced a noticeable
      depolarization of the olfactory epithelium, suggesting that these chemicals are
      not detected by the olfactory sense of the fish. These results are discussed in
      the light of the data concerning effects of pesticides on behavior and chemical
      communication in fish.

PMID- 11462144
TI  - Metabolic alterations without metal accumulation in the ovary of adult Bufo
      arenarum females, observed after long-term exposure to Zn(2+), followed by
      toxicity to embryos.
AB  - Long-term exposure of aquatic organisms to metals, even those considered
      micronutrients, may affect their metabolism and produce sublethal effects. We
      evaluated the effects of long-term exposure of adult amphibian (Bufo arenarum)
      females to 4 microg/L of Zn(2+) (ZnSO(4) x H(2)O) in Ringer solution on the
      concentration of Zn and Fe, the activity of the key enzyme of the pentose
      phosphate pathway glucose 6-phosphate dehydrogenase, and glutathione content,
      both in the liver and ovary of these animals. We also performed early embryonic
      development studies by in vitro insemination from control and treated females. Zn
      exposure rendered lower Zn concentrations in the ovaries than did exposure of
      animals to Ringer solution without metal addition (97 +/- 50 versus 149 +/- 46 Zn
      microg/wet tissue g). Zn and Fe concentration correlation was positive and linear
      in the ovary, but was negative and nonlinear in the liver of the studied females.
      The activity of the enzyme glucose 6-phosphate dehydrogenase decreased (0.0599 +/
      0.0109 versus 0.0776 +/- 0.0263 micromol of NADPH/min x mg of proteins) and the
      endogenous glutathione content increased (0.027 +/- 0.005 versus 0.018 +/- 0.007
      mg/10 mg of proteins) in the ovary but remained unaltered in the liver as a
      consequence of Zn treatment. Our results suggest the existence of different
      mechanisms of regulation of Zn and Fe concentrations in the ovary and in the
      liver of adult B. arenarum females. Binding of Zn to low-molecular-weight
      proteins, as metallothioneins, may occur in the liver, thus protecting this organ
      from toxic effects. In the ovary high-molecular-weight proteins, like glucose-6
      phosphate dehydrogenase, should be able to bind Zn, leading to oxidative stress
      responsible for the observed increase in endogenous glutathione content.
      Inhibition of the pentose phosphate pathway in the ovary by Zn can be responsible
      for the reproductive failure that we detected through embryos survival studies
      during early life stages: 81.3 +/- 6.3% of embryos from control females survived
      versus 63.1 +/- 13.8% of embryos from Zn-treated females at the branchial
      circulation stage of development.

PMID- 11462145
TI  - Lead toxicosis and trace element levels in wild birds and mammals at a firearms
      training facility.
AB  - In May 1999, lead poisoning was diagnosed in a yellow-rumped warbler (Dendroica
      coronata) and a gray squirrel (Sciurus carolinensis) found at the Federal Law
      Enforcement Training Center (FLETC), Glynn County, GA, based on detection of 6.2
      and 90.0 ppm wet weight (WW) lead in the liver of the warbler and squirrel,
      respectively. From October 21--26, 1999, 72 wild animals (37 mammals and 35
      birds), comprised of 22 different species, were collected from a 24-ha area
      surrounding the FLETC outdoor firearms shooting range complex to evaluate
      exposure to lead and other trace elements. Ten animals were used as controls
      (five mammals and five birds) and were collected from areas 1.5--3 km outside the
      shooting range area. Kidney and liver tissues were analyzed for lead, zinc, and
      other trace elements. Bird gizzards and white-tailed deer abomasums were examined
      grossly and radiographically to detect metallic objects. Twenty-four (33.3%)
      animals (11 species) had kidney or liver tissue lead levels > 1.00 ppm, and 12 of
      these (6 species) had levels > 2.00 ppm. Carcasses of one brown-thrasher
      (Toxostoma rufum) and two white-tailed deer (Odocoileus virginianus) contained
      lead fragments. Elevated liver tissue levels of zinc (111.0 ppm) were detected in
      one brown thrasher that also had elevated kidney and liver tissue lead levels. In
      February 2000, seven yellow-rumped warblers and one solitary vireo (Vireo
      solitarius) found dead near the FLETC firearms shooting range also were diagnosed
      with lead poisoning, with liver and kidney tissue lead levels from 1.77--11.6 and
      4.55--17.8 ppm WW, respectively. This frequency of elevated tissue lead levels
      among the animals examined, in combination with confirmed lead toxicosis in both
      avian and mammalian species at FLETC, indicates significant lead exposure of
      local wild bird and mammal communities via bullets and fragments in and on the
      soil surface of the four outdoor ranges. Most FLETC firearms training is being
      shifted to new baffled ranges (four walls with semiopen top) with bullet recovery
      capabilities to preclude future deposition of lead in the environment; existing
      outdoor ranges will be remediated to remove existing lead.

PMID- 11462146
TI  - Courtship behavior of captive American kestrels (Falco sparverius) exposed to
      polychlorinated biphenyls.
AB  - Polychlorinated biphenyls (PCBs) adversely affect reproduction in birds. Captive
      adult male and female American kestrels (Falco sparverius) were studied to
      investigate the potential behavioral and hormonal alterations during the
      courtship period resulting from clinical exposure to PCBs. American kestrels
      ingested 7 mg/kg/body weight/bird/day of a 1:1:1 mixture of Aroclors 1248, 1254,
      and 1260 through their diet of day-old cockerels. The dietary dosage of Aroclors
      resulted in environmentally relevant total PCB residues in the eggs, averaging
      34.1 microg/g wet weight (geometric mean). There was no difference between
      treatment and control birds in the circulating levels of total androgens (p =
      0.44) or in 17 beta-estradiol (p = 0.29), one week following pairing. Male
      kestrels exposed to dietary PCBs exhibited significantly more sexual behaviors (p
      = 0.034) and flight behaviors (p = 0.026) than the control males. Sexual
      behaviors of male kestrels included; nest-box inspections, solicitation of
      copulation, the offer of food to the female, and giving the female food. The
      flight behaviors of the male included; flying from one perch to another and
      aerial display. In addition, the frequency of male sexual behaviors were
      correlated (r = 0.605, p = 0.001) with total PCB residues in the eggs of their
      mates. A concurrent study found that these same PCB-exposed kestrels experienced
      a delay in clutch initiation as well as a greater number of completely infertile
      clutches.

PMID- 11462147
TI  - Anthropogenic and natural organohalogen compounds in blubber of dolphins and
      dugongs (Dugong dugon) from northeastern Australia.
AB  - A range of organohalogen compounds (10 polychlorinated biphenyl [PCB] congeners,
      DDT and metabolites, chlordane-related compounds, the potential natural
      organochlorine compound Q1, toxaphene, hexachlorobenzene, hexachlorocyclohexanes,
      dieldrin, and several yet unidentified brominated compounds) were detected in the
      blubber of four bottlenose dolphins (Tursiops truncatus), one common dolphin
      (Delphinus delphis), and seven dugongs (Dugong dugon), as well as in adipose
      tissue of a green turtle (Chelonia mydas) and a python (Morelia spilota) from
      northeast Queensland (Australia). The green turtle and dugongs accumulated lower
      organohalogen levels than the dolphins. Lower levels in dugongs were expected
      because this species is exclusively herbivorous. Highest PCB and DDT levels
      recorded in dugongs were 209 and 173 microg/kg lipids, respectively. Levels of
      the nonanthropogenic heptachlorinated compound Q1 (highest level in dugongs was
      160 microg/kg lipids) were estimated using the ECD response factor of trans
      nonachlor. Highest organohalogen levels were found in blubber of dolphins for
      sumDDT (575--52,500 microg/kg) and PCBs (600--25,500 microg/kg lipids).
      Furthermore, Q1 was a major organohalogen detected in all samples analyzed,
      ranging from 450--9,100 microg/kg lipids. The highest concentration of Q1
      determined in this study represents the highest concentration reported to date in
      an environmental sample. Levels of chlordane-related compounds were also high
      (280--7,700 microg/kg, mainly derived from trans-nonachlor), but concentrations
      of hexachlorobenzene, hexachlorocyclohexanes, dieldrin, and toxaphene were
      relatively low and contributed little to the overall organohalogen contamination.
      Furthermore, a series of three major (BC-1, BC-2, and BC-3) and six minor (BC-4
      through BC-9) unknown brominated compounds were observable by extracting m/z 79
      and m/z 81 from the GC/ECNI-MS full scan run. Structural proposals were made for
      the two major recalcitrant compounds (referred to as BC-1 and BC-2). BC-2 appears
      to be a tetrabromo-methoxy-diphenylether (512 u) and BC-1 has 14 u (corresponding
      with an additional CH(2) group) more relative to BC-1. In general, the
      organohalogen pattern observed in blubber of dolphins was different compared to
      similar samples from other locations in the world, which is apparent from the
      fact that the four major abundant signals in the GC/ECD chromatogram of D.
      delphis originated from the four unknown compounds Q1, BC-1, BC-2, and BC-3.

PMID- 11462148
TI  - Transgene expression of thioredoxin (TRX/ADF) protects against 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced hematotoxicity.
AB  - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has a variety of toxic effects on a
      number of organs, including the hematopoietic system. The importance of TCDD
      induced oxidative stress has been evaluated in several target organs. However,
      its role in hematotoxicity remains poorly understood, although bone marrow is
      known to produce reactive oxygen species. The aim of this study is to evaluate
      not only the contribution of oxidative stress to TCDD-induced hematotoxicity but
      also the protective function of TRX/ADF, a known anti-oxidative stress agent, on
      the hematotoxicity of TCDD in ADF wild-type (WT) and transgenic (Tg) mice. WT and
      Tg mice received a single intraperitoneal injection of 20 microg TCDD/kg. One day
      after the treatment, blood and bone marrow cellularity was measured and bone
      marrow levels of granulotyce/macrophage colony-forming units were determined in
      the in vitro colony assay. The expression of human TRX transgene by their bone
      marrow cells was analyzed by Western blot electrophoresis. Our results showed
      that overexpression of TRX/ADF protects against TCDD-induced hematotoxicity,
      indicating that induction of oxidative stress that results in disruption of redox
      regulation may be an important mechanism in TCDD-induced bone marrow toxicity.
      Moreover, we detected a significant decrease of AhR mRNA levels in bone marrow
      cells of Tg mice following TCDD treatment, suggesting a biological role of
      TRX/ADF in the AhR-mediated pathway through which TCDD induces oxidative stress.

PMID- 11462149
TI  - Environmental residues and biomonitoring estimates of human insecticide exposure
      from treated residential turf.
AB  - Intentional and unavoidable human exposure is a consequence of using pesticides
      to nurture and protect residential turf. Limited exposure studies have been
      conducted for assessing potential human exposure of turf residues. Exposure was
      measured in persons who performed a 20-minute structured activity (Jazzercise) on
      chlorpyrifos (CP)-treated Kentucky bluegrass (12 +/- 4 microg CP/cm(2)). CP
      exposure was measured by determining urine clearance of the 3,5,6-trichloro-2
      pyridinol (TCP). Study participants wore either 100% cotton whole body dosimeters
      (union suit, gloves, and socks) or exercise suits (shorts and a sports top or one
      piece suit with similar amounts of exposed skin). An average of 1.6 mg CP/person
      was extracted from whole body dosimeters worn by study participants. The measured
      residue transfer was well below the 35 mg CP/person estimated using the US EPA
      standard operating procedures. Biomonitoring based on urine clearance of TCP
      indicated that an average of 1.3 microg CP/kg was absorbed. Absorbed dosages (0.5
      to 2 microg CP/kg) derived from transferable residue on cotton cloths pressed to
      the turf with a weighted roller were similar to estimates from biomonitoring. A
      very limited amount of CP applied to turf is available for transfer and
      absorption during intensive human contact.

PMID- 11462150
TI  - Correlation between lead exposure indicators and sister chromatid exchange (SCE)
      frequencies in lymphocytes from inorganic lead exposed workers.
AB  - Inorganic lead exposure was studied in 31 volunteers employed in storage battery
      plant. The genotoxicity of lead was measured in terms of sister chromatid
      exchange (SCE). Erythrocyte delta-aminolevulinic acid dehydrogenase (ALAD)
      activity, urinary delta-aminolevulinic acid (U-ALA), and blood lead levels (PbBs)
      were also determined to evaluate some possible relations between these lead
      exposure indicators and the observed SCE frequencies. Blood lead concentration of
      36.31 microg/dl was determined as an average level in the workers. Consequently
      decreased ALAD activity in erythrocytes and increased U-ALA excretion was
      observed in statistically higher PbBs when compared with the control group. A
      statistically significant correlation was observed between the PbBs and SCE
      frequencies (p < 0.05). Moreover, the correlation between U-ALA excretion and SCE
      frequencies (p < 0.01) was relatively higher than the correlation between PbBs
      and SCE frequencies. These results might indicate a possible mechanism of ALA
      mediation in the genotoxic effects of lead.

PMID- 11462151
TI  - Environmental and physiological factors affecting lead and cadmium levels in
      deciduous teeth.
AB  - Shed deciduous teeth lead and cadmium content of children from Cartagena (Spain)
      was assessed. Parents were provided with an interview containing different
      questions concerning family socioeconomic status, child's health history, zone of
      residence, or home antiquity. Besides, physiological variables were considered,
      i.e., sex of donor, presence of caries, type of tooth donated, tooth weight, age
      of shedding, and position within the mouth. Tooth lead and cadmium data showed a
      positively skewed distribution and were log-normalized for further analyses. No
      statistically significant differences could be observed for lead and cadmium
      values according to the sex of donor. Both heavy metals decreased in content from
      incisors to molars and with age of shedding. The one-way analysis of variance
      (ANOVA) displayed both environmental and physiological risk factors contributing
      to high tooth lead and cadmium values. When a multifactor ANOVA was carried out,
      the associations between home antiquity, nail biting habit, and jaw with tooth
      lead levels, as well as those between zone of residence and tooth cadmium levels
      were found to persist. However, the only common factor for both heavy metals in
      the multiple analyses was the type of tooth.

PMID- 11462152
TI  - Hydrogen peroxide stimulates apoptosis in cultured human retinal pigment
      epithelial cells.
AB  - PURPOSE: To determine whether hydrogen peroxide (H2O2), a physiological mediator
      of oxidative stress induces apoptosis in retinal pigment epithelial (RPE) cells.
      METHODS: To demonstrate that oxidatively stressed retinal pigment epithelial
      cells undergo apoptosis consequential to mitochondrial dysfunction, biochemical
      parameters of apoptosis were determined in cultured cells after treatment with 50
      200 mM H2O2 for different times. Caspase-3 protease activity was determined from
      hydrolysis of DEVD-rho-nitroanilide. Expression of the anti-apoptotic protein,
      bcl-2 and the pro-apoptotic proteins p53 and p21 were analyzed by western
      blotting. RESULTS: Caspase-3 activity significantly increased in cells exposed to
      H2O2. Also, the expression of bcl-2 in cells treated with 200 microM H2O2 was
      diminished, whereas expression of p53 and p21waf-1 was increased compared to the
      controls. CONCLUSIONS: Exposure of retinal pigment epithelial cells to
      concentrations of H2O2 that cause in vitro mitochondrial DNA damage also promotes
      apoptosis.

PMID- 11462153
TI  - Mechanism of growth inhibitory effect of Mitomycin-C on cultured human retinal
      pigment epithelial cells: apoptosis and cell cycle arrest.
AB  - PURPOSE: To investigate the therapeutic potential of Mitomycin-C (MMC) in the
      management of proliferative vitreoretinopathy, the antiproliferative effect of
      MMC on cultured human retinal pigment epithelial (RPE) cells were investigated in
      vitro. METHODS: Drug sensitivities of cultured human RPE cells to MMC were
      determined using the tetrazolium dye assay. In order to detect the presence of
      apoptosis, DNA fragmentation was assessed by DAPI staining, and TdT-dUTP nick-end
      labeling (TUNEL) assay. The relative amount of DNA fragmentation was quantified
      by flow cytometric analysis. To analyze the cell cycle response of RPE cells to
      MMC, flow cytometric analysis of propidium iodide stained nuclei was performed.
      The levels of proteins related to DNA damage in the RPE cells were then
      determined by Western blot analysis. RESULTS: MMC inhibited cell proliferation in
      a dose-dependent manner. The majority of RPE cells following treatment with 10
      microg/ml of MMC exhibited fragmented nuclei as observed by DAPI staining and
      TUNEL assay. Cell cycle analysis demonstrated an accumulation of cells arrested
      in S and G2/M phase following treatment with 1 microg/ml of MMC. At 10 microg/ml
      of MMC, a dramatic increase of the cell population in the sub G1 peak, which can
      be considered a marker of cell death by apoptosis, was observed by flow
      cytometry. Western blot analysis of p53 and p21 revealed a gradual increase in
      the level of these proteins when RPE cells were exposed to increasing
      concentrations of MMC. CONCLUSIONS: This study demonstrated that the response of
      RPE cells to MMC was bi-directional: 1) partial arrest of the cell cycle at S,
      G2/M phase, and 2) induction of apoptotic cell death.

PMID- 11462154
TI  - Extra-hepatic expression of serum albumin mRNA in mouse retina.
AB  - PURPOSE: In some mammals, serum albumin protein exists in the interphotoreceptor
      space (IPS), the space between photoreceptor cells and the retinal pigment
      epithelium. Serum albumin is synthesized largely in the liver, though low levels
      of extra-hepatic expression have been documented in several other tissues,
      including fetal rat kidney, pancreas, lung, and heart. The purpose of this study
      was to investigate whether serum albumin protein and mRNA are found in mouse
      retina. METHODS: Using albumin rabbit antibodies and HRP goat anti-(rabbit IgG),
      we performed immunoassays on mouse IPS washes to detect the presence of serum
      albumin protein. Protein extracts from IPS washes were subjected to Affigel Blue
      chromatography. This resin has an affinity for serum albumin. Reverse
      transcription-polymerase chain reaction (RT-PCR) of retina total RNA was
      performed to search for albumin mRNA. Also, real-time reverse transcription
      polymerase chain reaction (RT-RT-PCR) was employed to look at the levels of
      expression in different age groups. RESULTS: A constituent of the IPS washes
      specifically bound and eluted from Affigel Blue column, suggesting that the
      washes contained serum albumin. SDS PAGE revealed that the size of the
      constituent was 67 kDa, the size of serum albumin. This 67 kDa band reacted with
      mouse serum antibody. An RT-PCR amplified fragment of serum albumin mRNA from
      retina displayed the expected size. The sequence of this fragment is identical to
      authentic serum albumin cDNA sequence. RPE and choroid were negative for serum
      albumin mRNA. However, rd1(-)/rd1(-) retina was positive, suggesting that at
      least some serum albumin is synthesized in the inner layers of the retina. RT-RT
      PCR showed that serum albumin mRNA levels in whole retina reached a maximum at
      about postnatal day 15 and gradually decreased to about one-sixth of maximum at
      12 months age. CONCLUSIONS: Serum albumin protein and mRNA were found in mouse
      IPS and retina, suggesting that the protein is synthesized in the retina. The
      previously demonstrated ability of serum albumin to bind fatty acids and
      retinoids and its presence in the mouse IPS suggest a role for serum albumin in
      transporting retinoids in the retina or IPS, especially at young ages when
      concentrations appear greatest.

PMID- 11462155
TI  - Vascular localization of heparan sulfate proteoglycans in retinas of patients
      with diabetes mellitus and in VEGF-induced retinopathy using domain-specific
      antibodies.
AB  - PURPOSE: The Steno hypothesis (Deckert et al. ) states that in diabetes mellitus
      (DM), changes in vascular heparan sulfate proteoglycan (HSPG) expression are
      involved in systemic endothelial dysfunction and increased capillary
      permeability. In diabetes-induced glomerular capillary leakage, loss of HSPG and
      its side chains has been documented. This study aimed to investigate whether
      microvascular leakage in diabetic retinopathy (DR) is also associated with
      altered expression of HSPG in retinal microvessels. METHODS: Serial cryosections
      of post-mortem eyes of 22 subjects with DM and 7 controls were stained with
      antibodies against the core proteins of the basement membrane HSPGs agrin (Abs
      Bl31 and JM72) and perlecan (Ab 1948), and four antibodies against heparan
      sulfate side chains (HS) (Abs JM403, HepSS1, JM13, 3G10). Moreover, we
      investigated Cynomolgus monkey eyes injected with vascular endothelial growth
      factor (VEGF)-A, as a model of retinal microvas-cular leakage. The endothelial
      antigen PAL-E was used to detect microvascular leakage. RESULTS: In the retina of
      all controls and DM cases, agrin and perlecan core proteins and HS as recognized
      by JM403 and 3G10 were expressed in the walls of microvessels. Staining for JM13
      was variable between cases, but unrelated to microvascular leakage as determined
      by PAL-E. Staining for HepSS1 was absent in all human retinal microvessels. In
      monkey retinas, HSPG staining was identical to that in human retinal tissues,
      except for the staining for HepSS1, which was found absent in control monkey eyes
      but which was positive in VEGF-injected eyes. CONCLUSIONS: Increased
      microvascular permeability in human DR is not associated with changes in
      expression of the HSPGs studied, whereas high amounts of VEGF may induce
      increased expression of the HS side chain epitope recognized by HepSS1. These
      results suggest that the mechanism underlying retinal leakage is different from
      diabetic glomerular capillary leakage.

PMID- 11462156
TI  - Latanoprost and matrix metalloproteinase-1 in human choroid organ cultures.
AB  - PURPOSE: Latanoprost, a prostaglandin F2a analogue and ocular hypotensive agent,
      alters extracellular matrix and matrix metalloproteinases (MMPs), including MMP
      1, within tissues of the uveoscleral outflow pathway. In addition to these
      tissues, the anterior choroid also is exposed to fluid within the uveoscleral
      outflow pathway. The present study was undertaken to compare MMP-1 expression in
      the choroid with other uveoscleral pathway tissues and to determine the effect of
      latanoprost on MMP-1 expression in human choroid organ cultures. METHODS: Choroid
      tissue explant cultures were generated and incubated with PhXA85, the
      biologically active form of latanoprost, or vehicle for 12 or 18 hours. Explant
      cultures from iris and ciliary body also were generated and exposed to PhXA85.
      Protein extracts of theses cultures, as well as from fresh tissues, were then
      probed for MMP-1 by Western blotting. All samples were normalized for protein
      content and reletive expression was evaluated by densitometry. Also, total RNA
      was harvested from fresh tissues or from cultures treated with PhXA85. The amount
      of MMP-1 mRNA in these samples was measured using real time polymerase chain
      reaction. These results were normalized according to simultaneous measurements of
      glyceraldehyde-3-phosphate dehydrogenase mRNA within the same samples. RESULTS:
      Compared to the ciliary body, in which specific MMP-1 concentration (/total mg
      protein) was greatest, the specific MMP-1 concentrations within iris, anterior
      choroid, and posterior choroid were less by 24.7 +/- 0.69%, 40.7 +/- 1.04%, and
      64.5 +/- 0.52%, respectively (mean +/- SD). The order of MMP-1 mRNA expression
      among these tissues from fresh eyes was ciliary body < anterior choroid <
      posterior choroid < iris. Treatment of ciliary body explant cultures with 200 nM
      PhXA85 for 12 hours increased MMP-1 protein content by 154 +/- 34% (P = 0.004,
      students t test, N = 3). In contrast, similar treatment of anterior choroid,
      posterior choroid, or iris explant cultures minimally changed MMP-1 protein
      content (23 +/- 22+/-, P = 0.124; 14 +/- 8%, P = 0.462; 27 +/- 16%, P = 0.037,
      respectively). Increased MMP-1 was observed in choroid cultures incubated for 18
      hrs with 200 nM or 500 nM PhXA85. MMP-1 mRNA in 12 hour PhXA85-treated choroid
      cultures was the same or less than vehicle-treated cultures from 7 of 9 donors.
      In contrast, MMP-1 mRNA was increased in PhXA85-treated ciliary body cultures
      from 2 of 2 donors. CONCLUSIONS: These results suggest that the capacity for
      latanoprost-mediated induction of MMP-1 within the choroid is less than within
      the ciliary muscle. Hence, it is unlikely that induction of MMP-1 in choroid
      plays as important a role in uveoscleral outflow modulation as induction of MMP-1
      in the ciliary muscle.

PMID- 11462157
TI  - Expression of Bcl-2 during the development of rabbit retina.
AB  - AIM: Programmed cell death or apoptosis plays an important role in retinal
      development. Bcl-2 is one of the genes whose endproducts regulate apoptosis. This
      study has examined the expression of Bcl-2 during the development of rabbit
      retina. METHOD: Bcl-2 was detected by immunohistochemistry in developing rabbit
      retinas from embryonic day (E) 15, 22, 26, 29 and postnatal day (PN) 0, 3, 7, 15
      and adults. RESULTS: Faint immunoreactivity in the anuclear layer was observed at
      E 15, which increased in E 19. Immunoreactivity in certain radially aligned
      neuroepithelial cells/immature Muller cells could be recognized at E 22 and it
      progressively increased until in mature Muller cells radial processes were
      immunoreactive beyond the outer plexiform layer in PN 15 retinas.
      Immunoreactivity was already present in the optic nerve at E 15 but it decreased
      with increasing age until it disappeared at the time of birth. CONCLUSIONS:
      Observations suggest that Bcl-2 is transiently expressed by ganglion cell axons
      during embryonic development. Detection of Bcl-2 immunoreactivity in the endfeet
      and proximal processes of radially aligned neuroepithelial cells/immature Muller
      cells early during the development, and its persistence in the endfeet and much
      of radial processes of Muller cells in adult life suggest that these cells
      possibly play a role in the development of the retinal ganglion cells, and also
      in the maintenance of the retinal neurons in the adults.

PMID- 11462158
TI  - Nitric oxide participates in cataract development in selenite-treated rats.
AB  - PURPOSE: The role of nitric oxide in the development of selenite-induced
      cataracts in rats was examined using nitric oxide synthase (NOS) inhibitors.
      METHODS: Subcutaneous injection of sodium selenite was used to induce cataracts
      in rats, with or without pretreatment with NOS inhibitors. The anterior eye
      segment analysis system (EAS-1000, Nidek) was used to measure lens opacity. The
      glutathione content of the lenses was determined by an HPLC method and the Ca2+
      content by atomic absorption spectrometry. Nitrite, a stable metabolite of nitric
      oxide, was determined fluorometrically. NADPH-diaphorase activity staining and
      Western blot analysis were used to determine NOS levels. RESULTS: Administration
      of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited lens
      opacification in selenite-treated rats. NG-nitro-d-arginine methyl ester, an
      inactive enantiomer of l-NAME, had no effect. Aminoguanidine, another NOS
      inhibitor, also inhibited the development of cataracts in a dose-dependent
      manner. On the other hand, L-arginine, a substrate of NOS, accelerated the
      development of cataracts. Although the opacification of the lenses was apparent
      approximately 3 days after selenite injection, the nitrite level was increased
      within one day. In addition, NOS was induced in the eye within one day of
      selenite injection. CONCLUSIONS: The present study demonstrated that NOS
      inhibitors prevented the development of cataracts in selenite-treated rats. The
      results also suggest that nitric oxide had an important role in the development
      of selenite-induced cataracts.

PMID- 11462159
TI  - Macular dystrophy with protan genotype and phenotype studied with cone type
      specific ERGs.
AB  - PURPOSE: To determine the L- and M-cone driven ERG responses in a male patient
      with macular dystrophy and a protan phenotype. METHODS: We measured large field
      ERG thresholds to stimuli which modulated exclusively the L- or the M-cones or
      the two in various combinations (both in-phase and in counterphase). In none of
      the stimuli, the S-cones were modulated. Additionally, standard and multifocal
      ERGs were measured. Analysis of the L- and M-cone pigment genes was performed by
      means of PCR, RFLP analysis and DNA sequencing techniques. RESULTS: Macular
      dystrophy was revealed by the markedly abnormal multifocal ERGs in presence of
      near normal standard ERGs. The large field ERG responses were exclusively driven
      by the M-cones with enlarged thresholds when compared with otherwise normal
      protanopes. In addition, the M-cone driven ERG response phases were abnormal.
      Pigment gene analysis confirmed a protan genotype with the presence of a single
      5'red/3'green hybrid pigment gene. CONCLUSIONS: Our novel stimulus technique
      allows a reliable analysis of the separate cone pathways even in cases with
      macular dysfunction. The increased thresholds and the abnormal phase behavior of
      the M-cone driven ERGs reflect altered mechanisms of the retinal physiology in
      this patient. The data strongly suggest that the macular dystrophy and the
      protanopia have independent origins.

PMID- 11462160
TI  - Lipid peroxidation in porcine irises: dependence on pigmentation.
AB  - PURPOSE: Pigmentation of the iris is caused by varying amounts of melanin pigment
      granula in a constant number of melanocytes in the superficial stroma. Melanin
      has been shown to act as antioxidant. We have now investigated lipid peroxidation
      in dependence on stromal pigmentation in isolated porcine irises. METHODS: The
      same number of lightly and heavily pigmented porcine irises (visual selection)
      were homogenized (1 : 20 w/v) in buffer (50 mmol/l phosphate buffer and 4 mmol/l
      sodium azide). 500 microl homogenate were incubated at 37 degrees C in duplicate
      for 5, 10, 20 and 40 min in absence and presence of Fe2+ as inducer of lipid
      peroxidation. The amount of lipid peroxidation was assayed by the thiobarbituric
      acid (TBA) test. The results are expressed as nmol of TBA reactive material
      (TBAR) produced/mg protein. Fe2+ concentration of the supernatant was determined
      spectrophotometrically with 1,10 orthophenanthroline. Concentrations of D-glucose
      and D -fructose in iris tissue homogenates were determined spectrophotometrically
      by enzymatic bioanalysis. RESULTS: 70, 180 and 360 micromol/l Fe2+ induced lipid
      peroxidation. A plateau region was reached after 20 min. The amount of lipid
      peroxidation differed in dependence on stromal pigmentation in porcine irises.
      The effect was most significant at 180 micromol/l Fe2+, which induced 1.373 +/-
      0.138 nmol TBAR/mg protein in lightly compared to 0.491 +/- 0.125 nmol TBAR/mg
      protein in heavily pigmented irises after 10 min incubation (p < 0.0001, n = 4).
      Similar effects (factor 2-3) were also measured after 20 and 40 min incubation.
      On the other hand, the content of Fe2+ in the supernatant was the same within
      error. Sugar concentrations (D-glucose and D-fructose) did not differ
      significantly for the two differently pigmented iris tissues. CONCLUSIONS: There
      is a stronger induction of lipid peroxidation in lightly compared to heavily
      pigmented porcine irises. This effect may be related to the difference in stromal
      melanin content and its antioxidant activity.

PMID- 11462161
TI  - A comparison of different embedding media on the ultrastructure of the trabecular
      meshwork.
AB  - PURPOSE: To determine whether the preservation of the extracellular matrix and
      the ultrastructural appearance of the trabecular meshwork are affected by
      different histologic processing protocols and embedding media. Conventionally
      used epoxy resins such as Araldite require complete dehydration of tissue, while
      the acrylic resin LR White requires only partial dehydration, better preserves
      tissue antigens, and has been reported to preserve more of the extracellular
      matrix. METHODS: Seven human eyes ranging in age from 2 months to 78 years were
      dissected and tissue samples from each eye processed and embedded in both
      Araldite and LR White media. The ultrastructure of the trabecular cells and the
      extracellular matrix of the meshwork was compared between media. The preservation
      of the extracellular matrix in the juxtacanalicular region was determined by
      measuring the amount of material immediately underlying Schlemm(1)s canal.
      Immunoelectron microscopy was used to determine the composition of this material.
      RESULTS: Araldite provided better resolution of ultrastructural details than
      freshly polymerized LR White. After a period of ripening for several months,
      however, resolution of tissue details in LR White improved. No significant
      quantitative difference was found in the amount of extracellular matrix
      underlying Schlemm's canal when comparing the two media. Neither post-mortem time
      to fixation (up to 31 hr), donor age, nor immersion vs. perfusion fixation
      technique affected the amount of extracellular material present in the comparison
      of the two embedding media. Immunogold labeling of the extracellular material
      within the juxtacanalicular tissue revealed the presence of collagen IV, laminin,
      and fibronectin in the basement membrane region immediately underlying the inner
      wall, and also in scattered patches within the juxtacanalicular tissue.
      CONCLUSIONS: Despite the less rigorous processing required for LR White than
      epoxy embedding, neither the appearance nor amount of the extracellular material
      was affected by the different embedding protocols. Prolonged post-mortem time to
      fixation did not affect the appearance nor amount of extracellular matrix.
      Immunolabeling revealed that the extracellular matrix of the juxtacanalicular
      tissue contains components of basement membrane material.

PMID- 11462162
TI  - Pigment epithelium derived factor as a neuroprotective agent against ischemic
      retinal injury.
AB  - PURPOSE: Pigment epithelium-derived factor (PEDF) is a protein shown to have
      neurotrophic activity. The purpose of this study was to determine whether PEDF is
      neuroprotective of retinal neurons that are exposed to transient ischemia
      reperfusion. METHODS: Transient retinal ischemia was produced by increasing the
      intraocular pressure for 45 min in albino rats eyes. Immediately after
      reperfusion, PEDF was injected intravitreally into the experimental eyes. Injury
      was evaluated morphologically and by measuring the thickness of the inner retinal
      layers (IRL) and by counting the number of retinal ganglion cells (RGC) in epon
      embedded sections. RESULTS: Morphologic and morphometric analysis of the
      thickness of the IRL and the counting of RGC demonstrated that PEDF injected
      immediately after reperfusion protected the eyes partially but significantly from
      the ischemic injury. CONCLUSIONS: Intravitreal injection of PEDF even after the
      ischemia can ameliorate retinal injury. PEDF may be useful in preventing neuronal
      degeneration in the inner retina resulting from ischemia.

PMID- 11462163
TI  - Delayed tear clearance in contact lens associated papillary conjunctivitis.
AB  - PURPOSE: To study the tear film clearance in contact lens associated papillary
      conjunctivitis patients. METHODS: Fifty-eight daily-wear soft contact lens
      wearers completed a questionnaire regarding a survey of their contact lens usage
      and subjective symptoms. They were grouped according to the size of conjunctival
      papillae, namely PC1 with no papillae, PC2 with papillae of less than 0.3 mm, and
      PC3 with papillae of 0.3-1.0 mm in diameter. Tear film breakup time and
      fluorescein clearance tests were performed. RESULTS: There was a median of 1, 2,
      and 3 subjective symptoms in PC1, PC2, and PC3 groups respectively (p < 0.001).
      Patients with larger papillae on their upper tarsus had more subjective symptoms
      such as burning sensation, discharge, limbal injection, foreign body sensation
      and dryness sensation (p = 0.018, 0.001, 0.004, 0.005, and 0.036 respectively).
      They also had shorter tear film breakup time (p = 0.05), delayed tear clearance
      (p = 0.002) and more corneal neovascularization (p < 0.001). Patients having
      delayed tear clearance test tended to have more subjective symptoms (p = 0.004)
      and larger papillae on upper tarsus (p = 0.002). However, neither the way the
      patients cleaned their contact lenses nor their enzyme cleaning frequency
      associated with the tear fluorescein clearance (p = 0.528 and 0.394,
      respectively). Meibomian gland dysfunction and corneal neovascularization did not
      correlate with the delayed tear clearance either (p = 0.111 and 0.717,
      respectively). CONCLUSIONS: Tear clearance in contact lens associated papillary
      conjunctivitis patients was delayed. We proposed that delayed tear clearance
      might increase the protein and inflammatory mediator concentrations in the tear
      film and contribute to the pathogenesis or aggravate the severity of contact lens
      associated papillary conjunctivitis.

PMID- 11462164
TI  - Retinal vascular changes in rats with inherited hypercholesterolemia--corrosion
      cast demonstration.
AB  - PURPOSE: To demonstrate specific hypercholesterolemic changes in the retinal
      vascular architecture. METHODS: Corrosion casts of 12- to 18-month-old rats with
      inherited hypercholesterolemia (RICO) and of control Wistar Kyoto (WKy) rats were
      examined with a scanning electron microscope (SEM). The diameters of the retinal
      arteries, veins and capillaries were measured in photographs with a caliber
      micrometer. The capillary branches were counted in the micrographs with the use
      of Adobe Photoshop. The retinal capillaries were examined by transmission
      electron microscopy (TEM). RESULTS: SEM examination of the vascular casts of 15
      month-old RICO rats showed slight tortuosity of large vessels at the posterior
      pole of the retina. The precapillary arterioles branching from the major artery
      were longer and straighter than normal. Retinal capillary changes such as caliber
      irregularity and narrowing in the capillary network were more severe in 18-month
      old RICO rats. The most prominent finding was marked straightening of the
      capillaries in the inner and outer layers of the capillary network, which looked
      like fine strings. Intercapillary spaces became wider, and finally capillaries
      looked scattered. The diameter of the retinal capillaries lumen in RICO rats was
      significantly narrower than that in WKy rats (p < 0.0001). The capillary branches
      were fewer in 18-month-old RICO rats than that in 18-month-old WKy rats (p <
      0.0001). Neither local stenosis or obstruction in the arterioles and venules nor
      any arteriovenous crossing defect was seen in young and old RICO rats.
      Transmission electron microscopy of 16-month-old RICO rat retinas revealed that
      the capillaries in the inner and outer plexiform layers contained scarce
      cytoplasmic components, vacuoles in endothelial cells and basement membranes of
      irregular thickness. Capillary pericytes were swollen and irregular in shape,
      contained vacuolated mitochondria and scarce cytoplasmic components. CONCLUSIONS:
      These findings indicate that the retinal capillary changes are probably related
      to hypercholesterolemia.

PMID- 11462165
TI  - Pseudomonas aeruginosa LasA protease and corneal infections.
AB  - PURPOSE: A mutant strain of Pseudomonas aeruginosa deficient in LasA protease
      (staphylolytic protease) has been described as having reduced ocular virulence,
      suggesting that LasA is a major virulence factor. This study was undertaken to
      provide further genetic analysis of the role of P. aeruginosa LasA protease in
      ocular infections. METHODS: LasA protease-deficient mutants of P. aeruginosa PAO1
      V and ATCC 19660 were constructed by allelic replacement. Mutants and their
      respective wild type parent strains were evaluated for virulence and growth in
      the eye using mouse scarification and rabbit intrastromal injection models of
      keratitis. RESULTS: LasA protease-deficient mutants of both strains were as
      virulent as wild type strains, growing to 4 to 6 log10 CFU/cornea and causing
      significant ocular pathology in the mouse (P > 0.42) and rabbit (P > 0.53).
      CONCLUSIONS: These data show that LasA protease is not a major corneal virulence
      factor, suggesting that the main mechanism of corneal damage has yet to be
      definitively identified.

PMID- 11462166
TI  - Optimal concentration of human epidermal growth factor (hEGF) for epithelial
      healing in experimental corneal alkali wounds.
AB  - PURPOSE: By using both in vivo and in vitro (organ-cultured) systems, the optimal
      concentrations of hEGF to enhance epithelial healing after alkali wounds were
      evaluated in the rabbit cornea. METHODS: Alkali-injured corneas (pi = 5.5 mm, 1 N
      NaOH, 60 s) were treated with 0.01, 0.1, 1.0, 10 and 100 ng/ml hEGF for the in
      vitro study. The healing of epithelium and endothelium was determined at 1, 2, 3,
      4, and 6 days after treatment. For the in vivo experiment, the eyes were treated
      with 2, 5, 10, and 50 microg/ml hEGF 3 times per day. The measurement of
      epithelial healing rate, transmission electron microscopy and immunohistochemical
      observation were performed after 7 days treatment. RESULTS: In in vitro tests,
      hEGF enhanced the epithelial healing rates, showing a maximum enhancement at the
      concentration of 1.0 ng/ml, and endothelial healing was increased at 100 ng/ml.
      In in vivo studies, no significant difference was observed in the rates of
      epithelial healing between control and each hEGF-treated group. Among the tested
      concentrations, 5 microg/ml hEGF induced the most active proliferation of basal
      cells and 50 microg/ml hEGF remarkably produced a vascular ingrowth to the
      central wound area. The thickness of re-surfaced epithelium was increased by hEGF
      in a concentration-dependent manner. CONCLUSIONS: The results of the present
      study indicate that a low concentration of hEGF may selectively enhance
      epithelial healing without affecting endothelial healing. The optimal
      concentration of hEGF for the stimulation of epithelial healing appears to be 5
      microg/ml in rabbit corneal alkali wounds.

PMID- 11462167
TI  - Calpain inhibitor, SJA6017, reduces the rate of formation of selenite cataract in
      rats.
AB  - PURPOSE: 1) To measure the amount of calpain inhibitor SJA6017 taken up by lenses
      of young rats after administration; and 2) To test efficacy of SJA6017 against
      selenite cataract in regard to amelioration of proteolysis of lens protein and
      prevention of lens nuclear opacity. METHODS: Selenite nuclear cataracts were
      produced by subcutaneous injection of an overdose of sodium selenite to 16-day
      old rats. SJA6017 was administered daily using intraperitoneal injections at 100
      mg/kg body weight/day for 4 days. Lenses were observed and photographed by slit
      lamp biomicroscopy, and scored into one of three stages. Enucleated lenses were
      also scored into one of four stages and lens opacities in the nuclear region were
      quantified by image analysis. Proteolysis of crystallins was detected by SDS
      PAGE. The amount of SJA6017 taken up by the lens was detected with a column
      switching HPLC system. RESULTS: Nuclear cataracts were visible in 31% of the
      animals receiving only selenite, while the frequency of nuclear cataract in the
      Se+SJA6017 group was reduced to only 16%. This effect of SJA6017 was confirmed by
      densitometric analysis as a reduction in the density of the nucleus. Similar
      proteolytic changes of crystallins occurred at all stages of selenite cataract
      formation. The amount of SJA6017 in the lens was detected at the level of 0.03
      microM. CONCLUSIONS: Systemic SJA6017 was taken up by the lens, and SJA6017
      ameliorated in vivo selenite cataract formation. These studies are important
      because they partially validate the biochemical rationale for developing non
      surgical, drug treatments for cataract prevention in man.

PMID- 11462168
TI  - Effect of external ocular surgery and mode of post-operative care on plasminogen,
      plasmin, angiostatins and alpha(2)-macroglobulin in tears.
AB  - PURPOSE: To determine whether corneal surgery and the mode of post-surgical
      treatment influence the distribution of plasminogen, plasmin, angiostatins and
      alpha(2)-macrogobulin in tear fluid. METHODS: Subjects underwent either
      photorefractive keratectomy (PRK), insertion of intra-stromal corneal rings
      (ICR), or cataract ablation followed by insertion of an intra-ocular lens (IOL).
      Post-surgical treatment consisted of prophylactic use of antibiotic and anti
      inflammatory agents followed either by patching for 24 hours, or covering the
      wounded cornea with a bandage soft contact lens. Open eye tear fluid (OTF) was
      obtained prior to surgery and 10 minutes after patch removal or 24 hours after
      surgery and thereafter with the bandage lens still in place. After
      centrifugation, supernatants and controls were western blot analyzed using a
      protocol designed to allow the simultaneous semi- quantitative detection of
      alpha2-macroglobulin, plasminogen, plasmin, angiostatins and interleukin-8 (IL
      8). RESULTS: No obvious differences were apparent in OTF recovered from
      contralateral control eyes compared to the surgical eyes in individuals who
      underwent PRK surgery and whose eyes were covered with a bandage contact lens. In
      contrast, OTF samples recovered 10 minutes after patch removal from all
      individuals contained elevated levels of alpha2-macroglobulin and a diverse
      mixture of elevated levels of plasminogen/plasmin, angiostatins and possibly a
      plasmin-a1-antiplasmin complex. All of these changes were seen, albeit to a
      lesser extent, in the patched control OTF samples. IL-8 could not be detected in
      any sample. The composition of the tear film returned to near normal on
      subsequent sampling 24 hours after patch removal. CONCLUSIONS: Patching results
      in a marked increase in the concentration of various proteins which could
      modulate inflammation and wound healing.

PMID- 11462169
TI  - Exogenous vasopressin influences intraocular pressure via the V(1) receptors.
AB  - PURPOSE: To compare central, peripheral, and ocular effects of exogenously given
      vasopressin on intraocular pressure (IOP) and to identify the related receptor
      mechanisms of action in rabbits. METHODS: Young adult New Zealand albino rabbits
      were entrained under a daily 12-hour light and 12-hour dark cycle. In the early
      light period, bolus injections of vasopressin or desmopressin (a specific V(2)
      receptor agonist) were given either to the central nervous system (CNS) through
      an implanted cannula to the 3(rd) ventricle or to the systemic circulation via
      the ear vein in conscious rabbits. Changes in IOP and pupil size were monitored
      for up to 6 hours and dose-response curves were generated. Effects of centrally
      and peripherally given vasopressin on IOP were further examined following
      pretreatments with a selective V(1) receptor antagonist administered into the
      3(rd) ventricle and into the ear vein, respectively. In order to clarify whether
      or not exogenously given vasopressin can alter IOP by mechanisms inside the eye,
      vasopressin was injected into the anterior chamber or the vitreous chamber
      unilaterally in conscious rabbits. Changes in IOP and pupil size were monitored.
      After an anterior chamber or intravitreal injection of the V(1) receptor
      antagonist, changes in IOP and pupil size due to an intravenous injection of
      vasopressin were determined to study the involvement of the related receptor
      mechanism. RESULTS: A dose-dependent elevation of IOP appeared after injections
      of vasopressin into the 3(rd) ventricle. There was no pupillary change. This IOP
      elevation was blocked by the pretreatment with the V(1) receptor antagonist.
      Following intravenous injections of vasopressin, significant reductions of IOP
      and pupil size occurred. These reductions were blocked by the pretreatment with
      the V(1) receptor antagonist. Intracerebroventricular or intravenous injection of
      desmopressin had no effect on IOP or pupil size. Injection of vasopressin into
      the anterior chamber or the vitreous chamber caused significant reductions of IOP
      and pupil size. Pretreatment with the V(1) receptor antagonist into the anterior
      chamber or the vitreous chamber prevented the reductions of IOP and pupil size
      following an intravenous injection of vasopressin. CONCLUSIONS:
      Intracerebroventricular and intravenous injections of vasopressin cause opposite
      effects on IOP. The central effect of vasopressin on IOP and the peripheral
      effects of vasopressin on IOP and pupil size are due to stimulations of the V(1)
      receptors. Reductions of IOP and pupil size following intravenous injections of
      vasopressin are at least partially due to stimulations of the V(1) receptors
      inside the eye.

PMID- 11462170
TI  - Uveitopathogenic sites in recoverin.
AB  - PURPOSE: This study was carried out in order to determine the most potent and
      novel uveitopathogenic sites of recoverin using synthetic peptides. METHODS:
      Several synthetic peptides containing the recoverin sequence plus adjuvants were
      injected into Lewis rats, and the uveitopathogenic sequence was defined,
      clinically, histologically, and immunologically. RESULTS: Peptides containing of
      amino acids 57-85 and 136-167 induced severe EAU, and the lowest doses to induce
      EAU were 20 microg and 10 microg, respectively. Lymphocyte proliferative
      reactions were also positive for peptides 57-85 and 136-167. The core sequences
      within the uveitopathogenic site were 65-79 and 153-164. Peptides of amino acids
      65-79 within 57-85 and 149-167 within 136-167 were the smallest in the recoverin
      sequence, respectively, that could induce severe EAU. CONCLUSION: We found
      recoverin has some novel potent uveitopathogenic sites, 149-167. These findings
      of the uveitopathogenic sites in recoverin may lead to improved understanding of
      the pathogenesis of uveitis and the means to design specific treatment.

PMID- 11462171
TI  - Cytokine production and helper T cell subsets in Vogt-Koyanagi-Harada's disease.
AB  - PURPOSE: To investigate helper T (Th) cell subsets and cytokine production in
      patients with Vogt-Koyanagi-Harada's (VKH) disease. METHODS: Nine patients in the
      acute stage of VKH disease and 9 healthy controls were studied. Interferon-gamma
      (IFN-gamma), interleukin-2 (IL-2) and IL-4 mRNA from peripheral blood mononuclear
      cells (PBMC) was detected by reverse transcriptase-polymerase chain reaction.
      Cytokine levels in plasma, cerebrospinal fluid (CSF) and PBMC culture supernatant
      were measured by enzyme-linked immunosorbent assay (ELISA). The proportions of
      each cytokine-producing CD4+ or CD8+ cells in PBMC cultured with or without anti
      CD3 antibody stimulation were analyzed by flow cytometry. RESULTS: We observed a
      significant increase of cytokine mRNA positive cases of VKH patients in
      comparison with controls only in IFN-gamma mRNA detection from PBMC. ELISA
      detected IFN-gamma in CSF from only 1 patient and no cytokine in plasma. The
      levels of IFN-gamma and IL-2 were significantly higher in the stimulated cell
      culture supernatant of the patients than those of controls. The proportions of
      IFN-gamma- or IL-2-producing CD4+ cells were significantly higher in the patients
      than in controls in both stimulated and unstimulated conditions. However, no
      significant difference was found in IL-4-producing CD4+ cells. In CD8+ cells,
      significant difference was found only in IL-2-producing cells in the stimulated
      condition. CONCLUSIONS: Th cells from VKH patients produced predominantly Th1
      cytokines, especially after stimulation in vitro. It is therefore suggested that
      activated Th cells produce predominantly Th1 cytokines, which then produce
      pathologic changes.

PMID- 11462172
TI  - Demethylation, reactivation, and destabilization of human fragile X full-mutation
      alleles in mouse embryocarcinoma cells.
AB  - The major causes of fragile X syndrome are mutational expansion of the CGG repeat
      in the FMR1 gene, hypermethylation, and transcriptional silencing. Most fragile X
      embryos develop somatic mosaicism of disease-causing "full" expansions of
      different lengths. Homogeneity of the mosaic patterns among multiple tissues in
      the same individual indicates that these previously unstable expansions acquire
      mitotic stability early in fetal life. Since mitotic stability is found strictly
      associated with hypermethylation in adult tissues, current theory has fixed the
      time of instability to developmental stages when fully expanded CGG repeats exist
      in an unmethylated state. We used murine embryocarcinoma (EC) cells (PC13) as a
      model system of pluripotent embryonic cells. Hypermethylated and unmethylated
      full expansions on human fragile X chromosomes were transferred from murine A9
      hybrids into EC cells, by means of microcell fusion. As demonstrated in the
      present study for the first time, even full expansion alleles that were fully
      methylated and stable in the donors' fibroblasts and in A9 became demethylated,
      reactivated, and destabilized in undifferentiated EC hybrids. When destabilized
      expansions were reintroduced from EC cells into A9, instability was reversed to
      stability. Our results strongly support the idea that fully expanded alleles are
      initially unstable and unmethylated in the human embryo and gain stability upon
      genetic or epigenetic change of the embryonic cells.

PMID- 11462173
TI  - p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split
      hand-split foot malformation suggest a genotype-phenotype correlation.
AB  - p63 mutations have been associated with EEC syndrome (ectrodactyly, ectodermal
      dysplasia, and cleft lip/palate), as well as with nonsyndromic split hand-split
      foot malformation (SHFM). We performed p63 mutation analysis in a sample of 43
      individuals and families affected with EEC syndrome, in 35 individuals affected
      with SHFM, and in three families with the EEC-like condition limb-mammary
      syndrome (LMS), which is characterized by ectrodactyly, cleft palate, and mammary
      gland abnormalities. The results differed for these three conditions. p63 gene
      mutations were detected in almost all (40/43) individuals affected with EEC
      syndrome. Apart from a frameshift mutation in exon 13, all other EEC mutations
      were missense, predominantly involving codons 204, 227, 279, 280, and 304. In
      contrast, p63 mutations were detected in only a small proportion (4/35) of
      patients with isolated SHFM. p63 mutations in SHFM included three novel
      mutations: a missense mutation (K193E), a nonsense mutation (Q634X), and a
      mutation in the 3' splice site for exon 5. The fourth SHFM mutation (R280H) in
      this series was also found in a patient with classical EEC syndrome, suggesting
      partial overlap between the EEC and SHFM mutational spectra. The original family
      with LMS (van Bokhoven et al. 1999) had no detectable p63 mutation, although it
      clearly localizes to the p63 locus in 3q27. In two other small kindreds affected
      with LMS, frameshift mutations were detected in exons 13 and 14, respectively.
      The combined data show that p63 is the major gene for EEC syndrome, and that it
      makes a modest contribution to SHFM. There appears to be a genotype-phenotype
      correlation, in that there is a specific pattern of missense mutations in EEC
      syndrome that are not generally found in SHFM or LMS.

PMID- 11462174
TI  - Park7, a novel locus for autosomal recessive early-onset parkinsonism, on
      chromosome 1p36.
AB  - Although the role of genetic factors in the origin of Parkinson disease has long
      been disputed, several genes involved in autosomal dominant and recessive forms
      of the disease have been localized. Mutations associated with early-onset
      autosomal recessive parkinsonism have been identified in the Parkin gene, and
      recently a second gene, PARK6, involved in early-onset recessive parkinsonism was
      localized on chromosome 1p35-36. We identified a family segregating early-onset
      parkinsonism with multiple consanguinity loops in a genetically isolated
      population. Homozygosity mapping resulted in significant evidence for linkage on
      chromosome 1p36. Multipoint linkage analysis using MAPMAKER-HOMOZ generated a
      maximum LOD-score of 4.3, with nine markers spanning a disease haplotype of 16
      cM. On the basis of several recombination events, the region defining the disease
      haplotype can be clearly separated, by > or =25 cM, from the more centromeric
      PARK6 locus on chromosome 1p35-36. Therefore, we conclude that we have identified
      on chromosome 1 a second locus, PARK7, involved in autosomal recessive, early
      onset parkinsonism.

PMID- 11462175
TI  - A decade (1989-1998) of pediatric invasive pneumococcal disease in 2 populations
      residing in 1 geographic location: implications for vaccine choice.
AB  - During 1 decade (1989-1998), data on invasive pneumococcal disease were collected
      prospectively to assess the burden of disease among Jewish and Bedouin children
      in southern Israel and the potential reduction in illness that can be achieved by
      using conjugate vaccines. Data on 513 children <15 years old with
      bacteriologically proven invasive pneumococcal disease were obtained. Among
      Jewish and Bedouin children <5 years old, incidence rates were 45 and 139 cases
      per 100,000 child-years of observation, respectively. Jewish and Bedouin children
      differed in clinical manifestations, seasonal patterns of disease, serotype
      distribution, and antibiotic susceptibility rates. The potential coverage by 7-,
      9-, and 11-valent conjugate vaccines is 41%, 67%, and 71%, respectively, for
      Jewish children and 22%, 63%, and 65%, respectively, for Bedouin children. The 9-
      and 11-valent pneumococcal conjugate vaccines have the potential to substantially
      decrease invasive pneumococcal disease in southern Israel.

PMID- 11462176
TI  - Detection of Aspergillus species in blood and bronchoalveolar lavage samples from
      immunocompromised patients by means of 2-step polymerase chain reaction: clinical
      results.
AB  - Bronchoalveolar lavage (BAL) samples from 67 patients who were at high risk for
      invasive aspergillosis were examined using a recently developed 2-step polymerase
      chain reaction (PCR) that detects </=10 fg of Aspergillus DNA in blood and BAL
      samples in vitro. Thirteen of these patients had PCR and diagnostic results
      positive for Aspergillus infection. Four patients with possible invasive
      aspergillosis also had positive PCR results, and the remaining 50 had negative
      PCR results. In addition, 907 blood samples from 218 high-risk patients were
      screened. Thirty-three patients with positive PCR results had invasive
      aspergillosis; 148 patients had PCR and diagnostic results that were negative,
      and 34 patients with positive PCR results had nonconclusive clinical data. Both
      blood and BAL testing were performed for 45 patients. All 8 patients with proven
      invasive aspergillosis showed concordance of positive PCR results. Our data
      suggest that this PCR method has possible clinical value for confirming and
      improving the diagnosis of invasive aspergillosis in high-risk patients.

PMID- 11462177
TI  - Antibiotic-resistant pneumococci carried by young children do not appear to
      disseminate to adult members of a closed community.
AB  - Although antibiotic-resistant pneumococci have been frequently detected among day
      care center (DCC) attendees, the transmission of these organisms to other members
      of the community has not been adequately studied. Nasopharyngeal cultures were
      obtained from 152 children and 244 adult members of a closed community (a
      kibbutz) in Israel. Serotyping, antibiogram, and pulsed-field gel electrophoresis
      were performed to determine the relatedness of isolated pneumococci. Twenty (30%)
      of the 66 isolates from children showed decreased susceptibility to penicillin
      and 9 isolates (14%) were resistant to > or =3 drugs. Of the 16 isolates from
      adults, 5 (31%) were intermediately resistant to trimethoprim-sulfamethoxazole.
      Resistant strains carried by DCC attendees were not isolated either from their
      parents or from other adult members of the community. Despite the high degree of
      interpersonal contact occurring in a closed community, resistant pneumococcal
      strains carried by DCC attendees do not appear to be easily transmitted to the
      adult population, which suggests the existence of an immunological barrier.

PMID- 11462178
TI  - Cost of hospitalization for and risk factors associated with vancomycin-resistant
      Enterococcus faecium infection and colonization.
AB  - The increase in costs of hospitalization for patients with drug-resistant
      infection may be associated with drug resistance itself or with the severity of
      the underlying illness that predisposes patients to acquire the drug-resistant
      infection. To address this issue, risk factors and cost of hospitalization were
      compared for patients infected or colonized with vancomycin-susceptible
      Enterococcus faecium (VSEF) or vancomycin-resistant E. faecium (VREF) in a large
      tertiary-care hospital in New York City. From January 1995 through December 1996,
      157 patients with VSEF and 262 patients with VREF were identified. CMI (case-mix
      index) was assigned to each patient as a measure of severity of illness, with a
      CMI of 1 considered to represent illness of average severity. For all patients
      who were assigned a CMI of <3, the cost per day of hospitalization for patients
      with VREF was significantly greater than that for patients with VSEF. However,
      for patients with a CMI of >3, there was no difference between cost of
      hospitalization for patients with VREF and that for patients with VSEF. These
      observations indicate that, although vancomycin resistance is associated with an
      increased cost of hospitalization for less severely ill patients with VREF,
      patients with severe underlying illness, regardless of vancomycin resistance,
      incur similar hospitalization costs.

PMID- 11462179
TI  - Detection of unsuspected cases of nosocomial transmission of tuberculosis by use
      of a molecular typing method.
AB  - The aim of this study was to use restriction fragment length polymorphism to
      detect unsuspected cases of nosocomial transmission of tuberculosis (TB) among
      patients who had been admitted to a university hospital. One hundred fifty-one
      samples of Mycobacterium tuberculosis isolated from patients with pulmonary TB
      were studied. The isolates from 37 patients (24.5%) defined 11 clusters. None of
      the patients infected with these cluster isolates had hospital stays that
      coincided with one another, and for 5.4% of the patients, the epidemiological
      link was clearly outside the hospital. Previous incarceration was associated with
      infection with cluster isolates. In addition, 109 patients without TB (41 of whom
      were infected with human immunodeficiency virus) who shared a room with patients
      who had TB were followed for 18-60 months. Among the patients who survived,
      secondary cases of TB due to nosocomial transmission were not detected.

PMID- 11462180
TI  - Polyclonal bacteremia due to gram-negative rods.
AB  - The frequency of, risk factors for, and outcome of polyclonal gram-negative
      bacteremia are still unknown. We investigated them in a prospective cohort study
      of patients for whom a blood culture yielded >/=1 species of gram-negative
      aerobic rod. For each patient, pulsed field gel electrophoresis (PFGE) was
      performed on 4 colonies of each morphologic type. Episodes of bacteremia were
      considered polyclonal if caused by >1 PFGE type of the same species. Ten (6.5%)
      of 153 investigated patients had polyclonal bacteremia. Bacteremia due to
      nonfermenting rods was the single significant risk factor for polyclonal
      bacteremia. Complications were equally frequent in all patient groups. However,
      patients with polyclonal bacteremia received more extensive antibiotic therapy
      than did patients with monoclonal bacteremia. Nearly 20% of episodes of
      bacteremia due to nonfermenting rods were polyclonal, but it remains unclear why
      nonfermenting rods were more likely to cause polyclonal bacteremia than were
      other gram-negative rods.

PMID- 11462181
TI  - Initial virological and immunologic response to highly active antiretroviral
      therapy predicts long-term clinical outcome.
AB  - Little is known about the long-term clinical outcomes for human immunodeficiency
      virus (HIV)-infected patients who have received highly active antiretroviral
      therapy (HAART). Determining factors associated with long-term clinical outcomes
      early in the course of treatment may allow modifications to be made for patients
      who are at a greater risk of treatment failure. To evaluate these factors, we
      studied 213 HIV-infected patients who had received HAART for at least 115 weeks.
      In the univariate analysis, virological response, which was measured as the
      change in virus load from baseline at month 3 of treatment, was the single best
      predictor of clinical outcome (relative hazard, 0.722; P=.001), independent of
      virological suppression. In the multivariate analysis, virological response and
      immunologic response, which was measured as an increase in CD4 cell count of >200
      cells/mm(3), resulted in better prediction of clinical outcomes than did use of
      either variable alone (P=.02). Our results indicate that changes in virus load
      and immunologic response together are good predictors of clinical outcome and can
      be assessed after the initiation of HAART, which would allow clinicians to
      identify patients early in the course of therapy who are at greater risk of
      negative outcome.

PMID- 11462182
TI  - Evaluation of zinc bacitracin capsules versus placebo for enteric eradication of
      vancomycin-resistant Enterococcus faecium.
AB  - Patients who are colonized with enteric vancomycin-resistant Enterococcus faecium
      (VREF) are a major reservoir for transmission of and infection with this
      organism. In a randomized, controlled study to assess the effectiveness of high
      dose bacitracin in the eradication of enteric VREF, 12 patients who were
      colonized with VREF were randomized to receive placebo (n=6) or orally
      administered zinc bacitracin (n=6) for 10 days. Posttreatment perirectal or stool
      cultures indicated that after 3 weeks, VREF had been eradicated from the stool of
      only 2 (33%) of 6 patients in each group. Of the 8 remaining patients who were
      still VREF-positive at 3 weeks after treatment, 5 (62%) had later evidence of
      spontaneous enteric eradication at 8 weeks. Further testing of VREF isolates
      revealed that a significant number (n=22, 76%) were resistant to bacitracin and
      that patients may have been colonized with multiple different VREF strains.
      Although bacitracin was not effective in the enteric eradication of VREF, the
      high rates of spontaneous eradication suggest that other host and environmental
      factors are more important in achieving long-term suppression or elimination of
      VREF colonization.

PMID- 11462183
TI  - Vancomycin-resistant Enterococcus faecium meningitis successfully managed with
      linezolid: case report and review of the literature.
AB  - Enterococci cause serious illness in immunocompromised patients and severely ill,
      hospitalized patients. Resistance to vancomycin has increased in frequency during
      the past few years. Limited therapeutic options are available for vancomycin
      resistant enterococcal infections and the optimum therapy has not been
      established. We report a case of nosocomial vancomycin-resistant Enterococcus
      faecium meningitis in the setting of hyperinfection with Strongyloides
      stercoralis that was successfully treated with linezolid. We also review the
      previously reported cases of vancomycin-resistant E. faecium meningitis.

PMID- 11462184
TI  - Macrolide-resistant Streptococcus pneumoniae and use of antimicrobial agents.
AB  - The prevalence of isolates of Streptococcus pneumoniae (pneumococcus) that are
      resistant to antimicrobial agents is increasing globally. We studied the
      connection between antimicrobial resistance of pneumococci and regional use of
      antimicrobial agents in Finland. In 1997, a total of 6106 pneumococcal isolates
      were identified in clinical microbiology laboratories in Finland. Most of the
      pneumococci were isolated from respiratory tract samples, 8% were from blood
      culture samples, and 0.5% were from cerebrospinal fluid samples. The regional
      levels of resistance for pneumococci in 1997 were compared with the regional
      rates of use of antimicrobial agents from 1995 through 1996. We found that
      resistance to macrolides correlated highly significantly with macrolide use
      (P=.006). A significant correlation was also found between resistance to
      trimethoprim-sulfamethoxazole and trimethoprim-sulfamethoxazole use (P=.043). We
      did not find a correlation between penicillin resistance and the use of any
      antimicrobial agent. The positive correlation between macrolide-resistant
      pneumococci and the use of macrolides is worrying, because macrolides are used
      worldwide in the treatment of patients with respiratory tract infections, which
      are often caused by pneumococci.

PMID- 11462185
TI  - Antibiotic selection of multiply resistant pneumococci.

PMID- 11462186
TI  - Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for
      Disease Control and Prevention (USA) and the Laboratory Centre for Disease
      Control (Canada).
AB  - Chlamydia pneumoniae has been associated with atherosclerosis and several other
      chronic diseases, but reports from different laboratories are highly variable and
      "gold standards" are lacking, which has led to calls for more standardized
      approaches to diagnostic testing. Using leading researchers in the field, we
      reviewed the available approaches to serological testing, culture, DNA
      amplification, and tissue diagnostics to make specific recommendations. With
      regard to serological testing, only use of microimmunofluorescence is
      recommended, standardized definitions for "acute infection" and "past exposure"
      are proposed, and the use of single immunoglobulin (Ig) G titers for determining
      acute infection and IgA for determining chronic infection are discouraged.
      Confirmation of a positive culture result requires propagation of the isolate or
      confirmation by use of polymerase chain reaction (PCR). Four of 18 PCR assays
      described in published reports met the proposed validation criteria. More
      consistent use of control antibodies and tissues and improvement in skill at
      identifying staining artifacts are necessary to avoid false-positive results of
      immunohistochemical staining. These standards should be applied in future
      investigations and periodically modified as indicated.

PMID- 11462187
TI  - Prospective assessment of the etiology of acute febrile illness after a tick bite
      in Slovenia.
AB  - A prospective study established the etiology of febrile illnesses in residents of
      Slovenia that occurred within 6 weeks after a tick bite. A combination of
      laboratory and clinical criteria identified 64 (49.2%) of 130 patients as having
      confirmed, probable, or possible cases of tickborne disease during 1995 and 1996.
      Of the 130 patients, 36 (27.7%) had laboratory evidence of tickborne
      encephalitis, all of whom had clinically confirmed disease. Evidence of infection
      with Borrelia burgdorferi sensu lato was identified in 26 patients; 10 (7.7%) had
      confirmed Lyme borreliosis. Of 22 patients with evidence of Ehrlichia
      phagocytophila infection, 4 (3.1%) had confirmed ehrlichiosis. Infection by
      multiple organisms was found in 19 (14.6%) of 130 patients. Patients with
      meningeal involvement (43 [72.3%] of 59) were more likely to have confirmed
      tickborne disease than were patients with illness of undefined localization (18
      [26.5%] of 68; P<.0001). Tickborne viral and bacterial infections are an
      important cause of febrile illness in Slovenia.

PMID- 11462188
TI  - Clinical and molecular characterization of vancomycin-resistant Enterococcus
      faecium strains during establishment of endemicity.
AB  - To characterize the molecular epidemiology of vancomycin-resistant Enterococcus
      faecium (VREF) in Tennessee, VREF isolates that were recovered from patients
      during a 3-year period at a tertiary care center and throughout the state were
      typed by means of pulsed-field gel electrophoresis. Clinical characteristics and
      outcomes of patients colonized or infected with different strain types were also
      examined. A total of 34 different strain types were identified. A single VREF
      strain (type O) predominated (63 [61%] of 103 single-patient isolates (i.e., 1
      isolate per patient) obtained from 7 different health care institutions). There
      were no significant differences between patients harboring type O strains and
      those harboring non-type O strains (P> or =.05). The rate of recovery of type O
      subtypes and strains other than type O increased over the 3-year study period.
      Establishment of VREF endemicity was initially characterized by clonal spread of
      type O strains. Subsequently, polyclonal dissemination may have been due to
      microevolutionary changes among type O strains.

PMID- 11462189
TI  - A nosocomial outbreak of fluoroquinolone-resistant Streptococcus pneumoniae.
AB  - Over the course of a 20-month period, in a hospital respiratory ward in which
      ciprofloxacin was often used as empirical antimicrobial therapy for lower
      respiratory tract infections (LRTIs), 16 patients with chronic bronchitis
      developed nosocomial LRTIs caused by penicillin- and ciprofloxacin-resistant
      Streptococcus pneumoniae (serotype 23 F). The minimum inhibitory concentration
      (MIC) of ciprofloxacin for all isolates from the first 9 patients was 4
      microg/mL, in association with a parC mutation. Isolates from the subsequent 7
      patients all had a ciprofloxacin MIC of 16 microg/mL, in association with an
      additional mutation in gyrA. The MICs for this isolate were 8 microg/mL of
      levofloxacin (resistant), 2 microg/mL of moxifloxacin and gatifloxacin
      (intermediately resistant), and 0.12 microg/mL of gemifloxacin. This outbreak
      demonstrates the ability of S. pneumoniae to acquire multiple mutations that
      result in increasing levels of resistance to the fluoroquinolones and to be
      transmitted from person to person.

PMID- 11462190
TI  - Vertebral osteomyelitis due to Candida species: case report and literature
      review.
AB  - Candida species uncommonly cause vertebral osteomyelitis. We present a case of
      lumbar vertebral osteomyelitis caused by Candida albicans and review 59 cases of
      candidal vertebral osteomyelitis reported in the literature. The mean age was 50
      years, and the lower thoracic or lumbar spine was involved in 95% of patients.
      Eighty-three percent of patients had back pain for >1 month, 32% presented with
      fever, and 19% had neurological deficits. The erythrocyte sedimentation rate was
      elevated in 87% of patients, and blood culture yielded Candida species for 51%.
      C. albicans was responsible for 62% of cases, Candida tropicalis for 19%, and
      Candida glabrata for 14%. Risk factors for candidal vertebral osteomyelitis were
      the presence of a central venous catheter, antibiotic use, immunosuppression, and
      injection drug use. Medical and surgical therapies were both used, and
      amphotericin B was the primary antifungal agent. Prognosis was good, with an
      overall clinical cure rate of 85%.

PMID- 11462191
TI  - Sabin monovalent oral polio vaccines: review of past experiences and their
      potential use after polio eradication.
AB  - After global eradication of polio is achieved, there will be a need for
      stockpiles of vaccine to combat potential outbreaks of poliomyelitis caused by
      (1) unforeseen release of polioviruses, (2) continued circulation of vaccine
      derived strains, or (3) prolonged replication of polioviruses in immunodeficient
      persons. We conducted a review of the literature to document the immunogenicity
      and safety of monovalent Sabin vaccines, considered ideal candidates for these
      situations. The National Library of Medicine archives were searched for the
      keywords "polio," "monovalent," and "vaccine." Seroconversion rates for
      monovalent Sabin type 1 ranged from 53% to 100% (median, 95%); for type 2, 77%
      100% (median, 93%); and for type 3, 52%-100% (median, 85%). The risk of vaccine
      associated poliomyelitis per million persons vaccinated ranged from.05 to 0.99
      (type 1), 0-0.65 (type 2), and 1.18-8.91 (type 3). Single-dose monovalent Sabin
      vaccines are highly immunogenic and safe and should be considered for stockpiles
      of vaccine to provide an effective response to potential outbreaks of
      poliomyelitis in the post-eradication period.

PMID- 11462192
TI  - Better control of antibiotic resistance.
AB  - This text summarizes the conclusions of the French Working Party to Promote
      Research to Control Bacterial Resistance, initiated by the French Institute for
      Public Health Surveillance. The goal was to identify and prioritize the research
      areas most pertinent to the evolution of antibiotic resistance. The working group
      was part of a nationwide consultation of experts in the field of bacterial
      resistance and was coordinated with 2 other groups addressing (1) the use and
      surveillance of resistance to antibiotics and (2) the control and prevention of
      resistance to antibiotics. The proposals were discussed at a meeting held on 13
      January 1999 by a large group of French microbiologists and clinicians who
      specialize in infectious diseases. The expert panel stressed that the
      determinants of evolution of antimicrobial resistance and the possibility of
      reversing this evolution are not completely known or understood. It emphasized
      the need for efforts to anticipate emergence of new resistances, to analyze the
      consequences of bacterial resistance, to develop rapid tests for determination of
      susceptibility to antibiotics, and to develop new antibiotics.

PMID- 11462193
TI  - Why shouldn't we determine the erythrocyte sedimentation rate?
AB  - A test that is meant to measure a given parameter is more likely to detect
      changes in that parameter if it is not affected by factors other than those which
      it is intended to quantitate. The clinical use of the laboratory test for
      determining the erythrocyte sedimentation rate is backed by nearly a century of
      experience. Although its nonspecificity is acknowledged, it has been used to
      quantitate the inflammatory process that underlies infectious, inflammatory, and
      neoplastic disorders. I believe that this venerable test is affected by too many
      factors in addition to that which we think we are measuring, to the point that
      its clinical usefulness is severely compromised.

PMID- 11462194
TI  - Fungal infections in older adults.
AB  - Invasive fungal infections have become an increasing problem in older adults.
      Infections with opportunistic fungi have increased because older patients are
      more likely to be considered for transplantation, receive aggressive regimens of
      chemotherapy for cancer, and take immunosuppressive drugs for nonmalignant
      diseases. In addition, healthy older adults are now more likely to travel
      extensively and to indulge in outdoor activities, which put them at risk for
      exposure to endemic mycoses. Although many of the clinical manifestations of
      fungal infections in older and younger adults are similar, there are aspects of
      histoplasmosis, aspergillosis, and cryptococcosis that are unique to older
      patients. Treatment of older adults with amphotericin B is difficult because of
      the intrinsic nephrotoxicity of the drug. Although they are less toxic, azoles
      must be used carefully for treatment of older adults, who are more likely to
      experience serious drug-drug interactions than are younger persons.

PMID- 11462195
TI  - Group B streptococcal disease in nonpregnant adults.
AB  - Group B streptococcal (GBS) disease in nonpregnant adults is increasing,
      particularly in elderly persons and those with significant underlying diseases.
      Diabetes, neurological impairment, and cirrhosis increase risk for invasive GBS
      disease. Skin, soft-tissue, and osteoarticular infections, pneumonia, and
      urosepsis are common presentations. Meningitis and endocarditis are less common
      but associated with serious morbidity and mortality. Disease is frequently
      nosocomial and may be related to the placement of an iv catheter. Recurrent
      infection occurs in 4.3% of survivors. Capsular serotypes Ia, III, and V account
      for the majority of disease in nonpregnant adults. Although group B streptococci
      are susceptible to penicillin, minimum inhibitory concentrations are 4-fold to 8
      fold higher than for group A streptococci. Resistance to erythromycin and
      clindamycin is increasing. The role of antibodies in protection against GBS
      disease in nonpregnant adults is unresolved. However, the immunogenicity of GBS
      vaccines being developed for prevention of neonatal disease should be assessed
      for adults who are at risk.

PMID- 11462196
TI  - Influence of human immunodeficiency virus infection on the course of hepatitis C
      virus infection: a meta-analysis.
AB  - Studies have shown that rates of liver disease are higher in persons who are
      coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      than they are in persons with HCV alone, but estimates of risk vary widely and
      are based on data for dissimilar patient populations. We performed a meta
      analysis to quantify the effect of HIV coinfection on progressive liver disease
      in persons with HCV. Eight studies were identified that included outcomes of
      histological cirrhosis or decompensated liver disease. These studies yielded a
      combined adjusted relative risk (RR) of 2.92 (95% confidence interval [CI], 1.70
      5.01). Of note, studies that examined decompensated liver disease had a combined
      RR of 6.14 (95% CI, 2.86-13.20), whereas studies that examined histological
      cirrhosis had a pooled RR of 2.07 (95% CI, 1.40-3.07). There is a significantly
      elevated RR of severe liver disease in persons who are coinfected with HIV and
      HCV. This has important implications for timely diagnosis and consideration of
      treatment in coinfected persons.

PMID- 11462197
TI  - Investigation of primary human immunodeficiency virus infection in patients who
      test positive for heterophile antibody.
AB  - In light of a recent report of 3 false-positive results of Epstein-Barr virus
      heterophile tests caused by HIV infection, we sought to assess the frequency of
      this occurrence. One hundred thirty-two positive heterophile antibody-tested
      serum samples were obtained from 2 tertiary care facilities in Boston to assess
      for HIV, and all tested negative for HIV plasma RNA. This study shows that false
      positive results of heterophile tests are not frequently associated with primary
      HIV infection.

PMID- 11462198
TI  - Tularemia epidemic in northwestern Spain: clinical description and therapeutic
      response.
AB  - This study describes the clinical characteristics of tularemia in Spain's first
      epidemic outbreak and the therapeutic response and compares the efficacy of 3
      antibiotics (streptomycin, ciprofloxacin, and doxycycline). For 142 cases of
      tularemia, the therapeutic failure rate was 22.5%; ciprofloxacin was the
      antibiotic with the lowest percentage of therapeutic failures and with the fewest
      side effects.

PMID- 11462199
TI  - Endocarditis caused by penicillin-resistant viridans streptococci: 2 cases and
      controversies in therapy.
AB  - Although penicillin-resistant viridans streptococci have been isolated from
      samples from the mouth, blood, and wounds in increasing numbers, viridans
      streptococci isolated from patients with endocarditis have remained sensitive to
      penicillin for the past 5 decades. We report the cases of 2 patients with
      penicillin-resistant viridans streptococcal endocarditis, review 6 other cases
      from the literature, and summarize 2 studies that used an animal model of
      penicillin-resistant viridans streptococcal endocarditis.

PMID- 11462200
TI  - Dengue fever: a harmful disease in patients with thrombocytopenia?
AB  - We describe 2 patients with autoimmune thrombocytopenic disease who developed
      classic dengue fever associated with serious bleeding and extremely low platelet
      counts (1000 cells/mm(3) and 3000 cells/mm(3), respectively). Such patients
      should be properly advised as to the possibility that common dengue fever may
      substantially enhance their risk for hemorrhagic complications.

PMID- 11462201
TI  - Mortality rates in comparative trials of formulations of amphotericin B.

PMID- 11462203
TI  - Tuberculosis drug serum levels.

PMID- 11462204
TI  - Good's syndrome: the association of thymoma with immunodeficiency.

PMID- 11462205
TI  - Mycobacterium bovis peritonitis mimicking ovarian cancer in a young woman.
AB  - We describe a 27-year-old woman with peritonitis due to Mycobacterium bovis that
      initially appeared to be ovarian cancer. Clinicians should include this disease
      in the differential diagnosis of ovarian cancer and should consider laparoscopic
      diagnosis in the appropriate epidemiologic setting.

PMID- 11462206
TI  - Ivermectin treatment of a traveler who returned from Peru with cutaneous
      gnathostomiasis.
AB  - We describe a 21-year-old patient who experienced a relapse of cutaneous
      gnathostomiasis after receiving initial treatment with albendazole and who had a
      successful outcome after receiving a short course of ivermectin for the relapse.
      This is the first reported case of gnathostomiasis acquired by a human in Peru.

PMID- 11462207
TI  - Bacteremia caused by Capnocytophaga species in patients with neutropenia and
      cancer: results of a multicenter study.
AB  - We investigated 28 cases of bacteremia caused by Capnocytophaga species that
      occurred during an 8-year period, most of which were in patients with hematologic
      malignancy and neutropenia. Infections were uncomplicated, without serious organ
      involvement and without any apparent source except ulcerations of the
      oropharyngeal mucosa, and only 1 isolate showed resistance to beta-lactam
      antibiotics; 9 of 16 isolates were resistant to ciprofloxacin.

PMID- 11462208
TI  - Does gene number really settle the nature versus nurture debate?

PMID- 11462209
TI  - Cycle-regulated genes and cell cycle regulation.
AB  - The transcriptional profile of the entire Caulobacter crescentus genome over a
      synchronous cell cycle was recently described. The analysis reveals a stunning
      553 cell-cycle-regulated genes or orfs, nearly 19% of the genome, including
      putative functions in virtually all biological activities. Over a quarter of
      these genes/orfs respond to the Caulobacter master regulator, CtrA, most of them
      apparently indirectly. The analysis confirms and extends earlier observations
      showing that many proteins involved in cell cycle functions are expressed at the
      cell age when they are needed. Conversely, the data suggest that proteins
      specifically expressed at a particular age may be involved in a process taking
      place then.

PMID- 11462210
TI  - Remembering silence.
AB  - Polycomb response elements (PREs) are regulatory switch elements that can direct
      the genes that they control to be either active or silenced. Once decided, this
      on or off state is maintained through subsequent cell divisions. We do not know
      how the switching works, or how it is copied to newly replicated chromosomes.
      Experiments that switch a silenced PRE to an active state have provided insights
      into both questions. A PRE switched experimentally can remember its previously
      silenced state and return to it after several cell divisions. In the most recent
      study of this phenomen on, the data show that several distinct variables affect
      the ability of PREs to "remember" and restore their previous state. The authors'
      interpretation of these results is discussed here.

PMID- 11462211
TI  - Molecular biology and anatomy of Drosophila olfactory associative learning.
AB  - Most of our current knowledge of olfactory associative learning in Drosophila
      comes from the behavioral and molecular analysis of mutants that fail to learn.
      The identities of the genes affected in these mutants implicate new signaling
      pathways as mediators of associative learning. The expression patterns of these
      genes provide insight into the neuroanatomical areas that underlie learning. In
      recent years, there have been great strides in understanding the molecular and
      neuroanatomical basis for olfaction in insects. It is now clear that much of the
      association between the conditioned stimuli and the unconditioned stimuli in
      olfactory learning occurs within mushroom bodies - third order olfactory neurons
      within the central brain. In this review, we discuss the nature of the behavioral
      tasks, the molecules, and the neuronal circuits involved in olfactory learning in
      Drosophila.

PMID- 11462212
TI  - Mechanisms and molecules in motor neuron specification and axon pathfinding.
AB  - The vertebrate nervous system performs the most complex functions of any organ
      system. This feat is mediated by dedicated assemblies of neurons that must be
      precisely connected to one another and to peripheral tissues during embryonic
      development. Motor neurons, which innervate muscle and regulate autonomic
      functions, form an integral part of this neural circuitry. The first part of this
      review describes the remarkable progress in our understanding of motor neuron
      differentiation, which is arguably the best understood model of neuronal
      differentiation to date. During development, the coordinate actions of inductive
      signals from adjacent non-neural tissues initiate the differentiation of distinct
      motor neuron subclasses, with specific projection patterns, at stereotypical
      locations within the neural tube. Underlying this specialisation is the
      expression of specific homeodomain proteins, which act combinatorially to confer
      motor neurons with both their generic and subtype-specific properties. Ensuring
      that specific motor neuron subtypes innervate the correct target structure,
      however, requires precise motor axon guidance mechanisms. The second half of this
      review focuses on how distinct motor neuron subtypes pursue highly specific
      projection patterns by responding differentially to spatially discrete attractive
      and repulsive molecular cues. The tight link between motor neuron specification
      and axon pathfinding appears to be established by the dominant role of
      homeodomain proteins in dictating the ways that navigating motor axons interpret
      the plethora of guidance cues impinging on growth cones.

PMID- 11462213
TI  - It ain't over till it's ova: germline sex determination in C. elegans.
AB  - Sex determination in most organisms involves a simple binary fate choice between
      male or female development; the outcome of this decision has profound effects on
      organismal biology, biochemistry and behaviour. In the nematode C. elegans, there
      is also a binary choice, either male or hermaphrodite. In C. elegans, distinct
      genetic pathways control somatic and germline sexual cell fate. Both pathways
      share a common set of globally acting regulatory genes; however, germline
      specific regulatory genes also participate in the decision to make male or female
      gametes. The determination of sexual fate in the germline of the facultative
      hermaphrodite poses a special problem, because first sperm then oocytes are
      produced. It has emerged that additional layers of post-transcriptional
      regulation have been imposed to modulate the activities of the global sex
      determining genes, tra-2 and fem-3; the balance between these activities is
      crucial in controlling sexual cell fate in the hermaphrodite germline.

PMID- 11462214
TI  - Pathways to photoreceptor cell death in inherited retinal degenerations.
AB  - The mutations that cause many forms of inherited retinal degenerations have been
      identified, yet the mechanisms by which these mutations lead to death of
      photoreceptor cells of the retina are not completely understood. Investigations
      of the pathways from mutation to retinal degeneration have focused on spontaneous
      and engineered animal models of disease. Based on the studies performed to date,
      four major categories of degeneration mechanism can be identified. These include
      disruption of photoreceptor outer segment morphogenesis, metabolic overload,
      dysfunction of retinal pigment epithelial cells, and chronic activation of
      phototransduction. Future investigations will likely identify additional
      mechanisms of photoreceptor damage. This review will summarize what has been
      learned from studying animal models of non-syndromic inherited retinal
      degenerations.

PMID- 11462215
TI  - Ethylene hormone receptor action in Arabidopsis.
AB  - Small gaseous molecules play important roles in biological signaling in both
      animal and plant physiology. The hydrocarbon gas ethylene has long been known to
      regulate diverse aspects of plant growth and development, including fruit
      ripening, leaf senescence and flower abscission. Recent progress has been made
      toward identifying components involved in ethylene signal transduction in the
      plant Arabidopsis thaliana. Ethylene is perceived by five receptors that have
      similarity to two-component signaling proteins. The hydrophobic amino-terminus of
      the receptors binds ethylene, and mutations in this domain both prevent ethylene
      binding and confer ethylene insensitivity to the plant; the carboxyl-terminal
      portion of the receptors has similarity to bacterial his tidine protein kinases.
      Genetic data suggest a model in which ethylene binding inhibits receptor
      signaling, yet precisely how these receptors function is unclear. Two of the
      receptors have been found to associate with a negative regulator of ethylene
      responses called CTR1, which appears to be a mitogen-activated protein kinase
      (MAPK) kinase kinase.

PMID- 11462216
TI  - Fertilin beta and other ADAMs as integrin ligands: insights into cell adhesion
      and fertilization.
AB  - One of the most important cell-cell interactions is that of the sperm with the
      egg. This interaction, which begins with cell adhesion and culminates with
      membrane fusion, is mediated by multiple molecules on the gametes. One of the
      best-characterized of these molecules is fertilin beta, a ligand on mammalian
      sperm and one of the first ADAMs (A Disintegrin and A Metalloprotease domain) to
      be identified. Fertilin beta (also known as ADAM2) participates in sperm-egg
      membrane binding, and it has long been hypothesized that this function is
      achieved through the interaction of the disintegrin domain of fertilin beta with
      an integrin on the egg surface. There are now approximately 30 members of the
      ADAM family and, to date, five different ADAMs (fertilin beta, ADAM9, ADAM12,
      ADAM15, ADAM23) have been described to interact with integrins (specifically
      alpha(6)beta(1), alpha(v)beta(3), alpha(9)beta(1), alpha(v)beta(5), and/or
      alpha(5)beta(1)). This field will be discussed with respect to what is known
      about specific ADAMs and the integrins with which they interact, and what the
      implications are for sperm-egg interactions and for integrin function. These data
      will also be discussed in the context of recent knockout studies, which show that
      eggs lacking the alpha(6) integrin subunit can be fertilized, and eggs lacking
      the integrin-associated tetraspanin protein CD9 fail to fertilize. Key issues in
      cell adhesion that pertain to gametes and fertilization will also be highlighted.

PMID- 11462217
TI  - Does neuronal loss in Parkinson's disease involve programmed cell death?
AB  - Recently it has been hypothesized that apoptotic cell death is involved in
      several neuropathological conditions including Parkinson's disease (PD). Initial
      morphological studies assessing the presence of apoptosis in Parkinsonian brain
      tissues yielded mixed results. Based on more recent studies in human PD brains as
      well in animal and cell culture models of the disease, a picture is emerging,
      however, that strongly suggests that many of the molecular players thought to
      participate in this type of neuronal cell death are active in the disease. The
      task of researchers in the field is now to deduce how these players may be
      interacting with one another to bring about cell death in PD and to design
      effective therapies to interfere with these processes.

PMID- 11462218
TI  - An evolutionary model for the origin of non-randomness, long-range order and
      fractality in the genome.
AB  - We present a model for genome evolution, comprising biologically plausible events
      such as transpositions inside the genome and insertions of exogenous sequences.
      This model attempts to formulate a minimal proposition accounting for key
      statistical properties of genomes, avoiding, as far as possible, unsupportable
      hypotheses for the remote evolutionary past. The statistical properties that are
      observed in genomic sequences and are reproduced by the proposed model are: (i)
      deviations from randomness at different length scales, measured by suitable
      algorithms, (ii) a special form of size distribution (power law distribution)
      characterising different levels of genome organisation in the non-coding, and
      (iii) extensive resemblance in the alternation of coding and non-coding regions
      at several length scales (self-similarity) in long genomic sequences of higher
      eukaryotes.

PMID- 11462219
TI  - Oligotrophs versus copiotrophs.
AB  - Bacteria can grow rapidly, yet there are some that grow slowly under apparent
      optimal conditions. These organisms are usually present in environments with low
      levels of nutrients, and are not found in conditions of more plentiful nutrients.
      They are known as "oligotrophs"in contrast to "copiotrophs", which are common in
      environments with greater nutritional opportunities. This essay asks why do the
      oligotrophs not occupy richer environments, and why are copiotrophs not more
      prevalent in chronic starvation environments?

PMID- 11462220
TI  - Gene therapy and retinitis pigmentosa: advances and future challenges.
AB  - It may be possible, one day, to use gene therapy to treat diseases whose genetic
      defects have been discerned. Because many genes responsible for inherited eye
      disorders within the retina have been identified, diseases of the eye are prime
      candidates for this form of therapy. The eye also has the advantage of being
      highly accessible with altered immunological properties, important considerations
      for easy delivery of virus and avoidance of systemic immune responses. Currently,
      adenovirus, adeno-associated virus and lentivirus have been used to successfully
      transfer genetic material to retinal pigment epithelium and photoreceptor cells.
      By harnessing therapeutic genes to these viruses, researchers have been able to
      demonstrate rescue in rodent models of retinitis pigmentosa, providing evidence
      that this form of therapy can be effective in delaying photoreceptor cell death.
      Future challenges include confirming therapeutic effects in animal models with
      eyes more anatomically similar to those of humans and demonstrating long-term
      rescue with minimal toxicity.

PMID- 11462221
TI  - TMOF-like factor controls the biosynthesis of serine proteases in the larval gut
      of Heliothis virescens.
AB  - Proteolytic enzyme biosynthesis in the midgut of the 4th instar larva of
      Heliothis virescens is cyclical. Protease activity increases immediately after
      the molt from the 3rd to the 4th instar larvae and declines just before the molt
      into the 5th instar. Characterization of the midgut proteases using soybean
      tryspin inhibitor (SBTI) Bowman Birk Inhibitor (BBI) 4-(2
      aminoethyl)benzensulfonylfluoride (AEBSF) and N-tosyl-L-phenylalanine
      chloromethylketone (TPCK) indicate that protease activity is mostly trypsinlike
      (80%) with a small amount of chymotrypsinlike activity (20%). Injections of late
      3rd and 4th instar larval hemolymph into H. virescens larvae inhibited tryspin
      biosynthesis in the larval midgut. Similar results were obtained when highly
      purified 4th instar larval hemolymph that crossreacted with Aea-TMOF antisurm
      using ELISA was injected into 2nd instar larvae. Injections of Aea-TMOF and its
      analogues into 2nd instar, and Aea-TMOF alone into 4th instar larvae stopped
      trypsin biosynthesis 24 and 48 h after the injections, respectively. Injections
      of 4th instar H. virescens larval hemolymph into female Aedes aegypti that took a
      blood meal stopped trypsin biosynthesis and egg development. These results show
      that the biosynthesis of trypsin-like enzymes in the midgut of a lepidoptera is
      modulated with a hemolymph circulating TMOF-like factor that is closely related
      to Aea-TMOF. Arch.

PMID- 11462222
TI  - Testis ecdysiotropin, an insect gonadotropin that induces synthesis of
      ecdysteroid.
AB  - Testes of lepidoptera synthesized ecdysteroid in a somewhat different temporal
      pattern than the prothoracic glands that release ecdysteroid to the hemolymph.
      Brain extracts from Heliothis virescens and Lymantria dispar induced testes to
      synthesize ecdysteroid, but did not affect prothoracic glands. The testis
      ecdysiotropin (LTE) was isolated from L. dispar pupal brains by a series of high
      pressure chromatography steps. Its sequence was Ile-Ser-Asp-Phe-Asp-Glu-Tyr-Glu
      Pro-Leu-Asn-Asp-Ala-Asp-Asn-Asn-Glu-Val-Leu-Asp-Phe-OH, of molecular mass 2,473
      Daltons. The predominant signaling pathway for LTE was via G(i) protein, IP3,
      diacylglycerol and PKC; a modulating pathway, apparently mediated by an
      angiotensin II-like peptide, was controlled via G(s) protein, cAMP, and PKA.
      Testis ecdysteroid caused isolated testis sheaths to also synthesize a growth
      factor that induced development of the male genital tract. The growth factor
      appeared to be a glycoprotein similar to vertebrate alpha-1-glycoprotein. A
      polyclonal antibody to LTE indicated LTE-like peptide in L. dispar brain medial
      neurosecretory cells, the suboesophageal, and other ganglia, and also in its
      target organ, the testis sheath. LTE immunoreactivity was also seen in testis
      sheaths of Rhodnius prolixus. LTE-like immunoactivity was also detected in
      developing optic lobes, antennae, frontal ganglia, and elongating spermatids of
      developing L. dispar pupae. This may indicate that LTE has a role in development
      as well as stimulation of testis ecdysteroid synthesis. Published 2001 Wiley
      Liss, Inc.

PMID- 11462223
TI  - FMRFamide-like material in the earwig, Euborellia annulipes, and its functional
      significance.
AB  - The neurosecretory system of the earwig, Euborellia annulipes, contained material
      similar to that of FMRFamide, as shown by immunocytochemistry. Within the brain
      were two pairs of darkly staining perikarya in the medial protocerebrum, and up
      to four pairs of immunoreactive cells in the lateral protocerebrum. The corpora
      allata appeared immunoreactive in 10-day females, but not in 2-day-old adults.
      Additionally, immunoreactive material was detected in midgut endocrine cells of
      both 2- and 10-day-old females. FMRFamide at 1 to 100 nM did not inhibit juvenile
      hormone production by earwig corpora allata in vitro. This was true of glands of
      low activity from 2-day cat food-fed or starved virgin females, 10-day starved
      females, and those of relatively high activity from 10-day-old, cat food-fed
      females. In contrast, FMRFamide at 50 and 100 (but not at 1) nM stimulated gut
      motility in vitro in distended guts from 2-day fed females. Preparations from
      starved females and those from 10-day fed females (in which feeding behavior is
      on the decline) did not respond to exogenous FMRFamide with enhanced rates of
      contraction. Lastly, preparations from females starved for 7 days and
      subsequently fed for 3 days responded to 10 nM FMRFamide with increases in gut
      motility.

PMID- 11462224
TI  - Synthesis of lipids in the fat body of Gryllus bimaculatus: age-dependency and
      regulation by adipokinetic hormone.
AB  - The free abdominal fat body of adult female Mediterranean field crickets, Gryllus
      bimaculatus, synthesizes lipids from [1-(14)C]-acetate in vitro. Up to an age of
      12h, the incorporation of acetate into lipids is very low and then rises to a
      maximum 24h after adult emergence. Thereafter, the incorporation of acetate
      decreases to moderate levels at day 2 and then slowly decreases until day 30. The
      adipokinetic hormone of G. bimaculatus (Grb-AKH) significantly inhibits the
      incorporation of acetate at a concentration of 10(-11) M; maximum inhibition
      (approximately 95%) is reached at 10(-8) M. The inhibiting effect of Grb-AKH is
      fast, dose-dependent, and reversible. The periovaric fat body shows a similar
      pattern of acetate incorporation, although rates of incorporation are lower; the
      incorporation can be inhibited by Grb-AKH as well. The segmental abdominal fat
      body and the fat body from the head both incorporate acetate into lipids at low
      rates that cannot be inhibited significantly by AKH. Prepurified brain extracts
      significantly inhibit acetate incorporation by free abdominal fat bodies at a
      concentration of 0.1 brain equivalent. Allatostatins and crustacean cardioactive
      peptide, which are both present in cricket brains, are not responsible for this
      inhibiting effect. Octopamine causes a dose-dependent inhibition of acetate
      incorporation whereas synephrine had no such effect. The inhibiting effect of Grb
      AKH on the formation of lipid stores in the fat body and its consequences for
      reproductive processes are discussed.

PMID- 11462225
TI  - Introduction: neuropeptides in insect development and reproduction.

PMID- 11462226
TI  - Cancer and children: where are we coming from? Where are we going?
AB  - The past four decades have seen remarkable progress in the treatment of childhood
      cancer and changes in the social environment in which cancer in the family is
      experienced. Current research in pediatric psycho-oncology focuses on
      psychosocial consequences of the disease and on differentiating which factors
      predict problematic versus positive outcomes in adjustment of the child and the
      family. The papers in this Special Issue reflect much of the recent developments
      in childhood psycho-oncology as well as the challenges to come.

PMID- 11462227
TI  - Physical sequelae and self-perceived attachment in adult survivors of childhood
      cancer.
AB  - The association between the physical sequelae of childhood cancer and self
      reported attachment behavior was investigated in 97 adult survivors. Attachment
      was assessed using standardized self-report questionnaires. Functional disability
      and cosmetic sequelae of the cancer and its treatment were evaluated by the
      attending oncologist using a standardized rating scale. Results suggest that
      attachment is not significantly associated with physician-rated physical
      sequelae, but may be related to the time of onset of the functional deficits,
      independent of the current age or age at diagnosis. Further, survivors with
      functional sequelae in adulthood describe themselves as more insecure in their
      relationships in general and more ambivalent in their relationship with their
      parents. These findings, if replicated, suggest that the duration of the
      functional deficits as well as the developmental stage of the individual when
      they began may be important variables which affect the survivor's capacity to
      develop and maintain intimate relationships that are secure and satisfying.

PMID- 11462228
TI  - Predictors of affective responses of mothers and fathers of children with cancer.
AB  - We investigated predictors of affective responses for 125 parents (77 mothers, 48
      fathers) of children with various types of cancer who varied in time of diagnosis
      from newly diagnosed to 13 years following cancer treatment. The primary
      rationale of the investigation was to determine whether cognitive appraisals,
      perceived social supports, and caregivers' perceptions of children's behavior
      would predict affective responses differentially for mothers and fathers. We
      defined affectivity as self-reported depressive symptoms, and state and trait
      anxiety symptoms. Parents did not differ on any of the variables, including
      affective responses, although differential predictors of affective responses were
      revealed for mothers and fathers. Affiliation-related attributions were
      associated with affective responses for mothers, and achievement-related
      attributions and perceived social support were associated with affective
      responses for fathers.

PMID- 11462229
TI  - Children with cancer with different survival perspectives: defensiveness, control
      strategies, and psychological adjustment.
AB  - The main objective of the present study was to investigate whether children with
      cancer with different survival perspectives differ in their psychological
      adjustment, defensiveness and their use of cognitive control strategies.
      Furthermore, the study investigated which variables predict emotional adjustment
      of these children with cancer most adequately. A total of n=84 children (n=43
      children in remission and n=41 children not in remission) participated in the
      study. They answered questionnaires about control strategies, defensiveness,
      anxiety and depression. No differences were found in any of the questionnaires
      between children in remission and relapse. Emotional adjustment of the children
      was predicted by defensiveness and by positive expectations about the course of
      the illness. The findings demonstrate the importance of having positive
      expectations for the emotional adjustment of children with cancer. The strength
      of the study is the inclusion of a substantial group of children with cancer who
      have a reduced survival perspective.

PMID- 11462230
TI  - Supportive groups for siblings of pediatric oncology patients: impact on anxiety.
AB  - Childhood cancer can have a substantial emotional impact on the siblings of the
      sick child. In order to help these siblings adjust to the illness, supportive
      groups were started in 1994 at our medical center. The program is based on a
      model of psychosocial support; the aim of the group is to enhance control
      strategies and, thus, to reduce anxiety. It consists of five sessions and is
      offered to siblings aged 7-18. The study objective is to evaluate the effect of
      group participation on sibling anxiety. The State Trait Anxiety Inventory for
      Children was administered to 24 siblings before and after group participation.
      Results showed that siblings experience less anxiety after participating in the
      group. Before group participation, a majority of the siblings were more anxious
      compared with normal peers. The sibling's age and sex, whether the ill child is
      in treatment, survival perspective, and time since diagnosis were not related to
      anxiety reduction. The continuation of the group is supported by its positive
      impact on siblings. Results must nevertheless be interpreted cautiously,
      considering the small number of siblings participating in the study, the lack of
      a control group and the restriction to one outcome measure.

PMID- 11462231
TI  - Parental coping with the diagnosis of childhood cancer: gender effects,
      dissimilarity within couples, and quality of life.
AB  - OBJECTIVE: Considering coping as dynamic process within the family, effects of
      gender and diagnosis are investigated. Dissimilarity within couples in coping
      with childhood cancer is studied longitudinally in its effects on quality of life
      of mothers, fathers, and the sick children. METHODS: A total of 108 parents out
      of 54 complete families participated in a prospective study. Twenty-five families
      had a child newly diagnosed with cancer, 29 families had a child newly diagnosed
      with juvenile diabetes or epilepsy. The Coping Health Inventory for Parents, the
      Trier Coping Scales, and the Ulm Quality-of-Life Inventory for Parents were
      employed 1-2 weeks after diagnosis and again 10-12 weeks after diagnosis.
      RESULTS: In face of childhood cancer, parents develop more rumination, defense,
      and information seeking, and less social support seeking strategies compared to
      the control group. Mothers report more frequent and more effective coping
      compared with fathers, but mothers and fathers do not differ in their self
      reported quality of life. No convergence within couples could be demonstrated in
      most of the corresponding coping styles. The strongest correlation between
      mothers and fathers appeared in the religious coping style (r=0.60, p<0.001).
      Coping dissimilarity within couples in social support seeking and religion is
      correlated with an improvement of parental quality of life. Parental
      dissimilarity in information seeking is correlated with a decrease in the child's
      quality of life. CONCLUSION: Coping dissimilarities between fathers and mothers
      have differential effects on the family members. For this reason, psychosocial
      interventions should support dis-synchrony when it appears adaptive, and they
      should help parents to overcome those differences that negatively affect their
      child.

PMID- 11462232
TI  - Psychological issues among children of hereditary breast cancer gene (BRCA1/2)
      testing participants.
AB  - Children growing up in hereditary breast cancer families may experience
      diminished psychological well-being. In addition to coping with having a cancer
      affected parent or close relatives, these children may focus on their own health
      risks in light of shared genetic information. While knowledge of a parent's
      BRCA1/2 negative status may allay a subset of children's worries and fears about
      cancer, others could experience distressing thought patterns over positive test
      results. The purpose of this preliminary study is to explore conceptions of
      health, cancer risk, and psychological adjustment among children in families
      suggestive of carrying BRCA1/2 susceptibility genes. As part of a longitudinal
      investigation of the outcomes of BRCA1/2 testing in adults, 20 children of a
      highly select group of 15 mothers (80% previously affected by breast/ovarian
      cancer) completed a self-report survey of their beliefs and opinions regarding
      cancer and genetic testing, stress and worry about cancer, and anxiety,
      depression, and behavior problems. All information was completed at baseline,
      prior to the mother's receipt of her genetic test result. The data did not
      suggest unusually elevated cancer worries or psychological adjustment problems in
      these children at this point in the parental genetic testing process. However,
      children with more psychological distress symptoms did experience more frequent
      thoughts of becoming sick and greater cancer worries. To the extent that learning
      about a parent's positive test result could exacerbate these tendencies,
      recommendations to promote child psychological and family communications research
      that monitor such responses are offered.

PMID- 11462233
TI  - Using linked markers to infer the age of a mutation.
AB  - Advances in sequencing and genotyping technologies over the last decade have
      enabled geneticists to easily characterize genetic variation at the nucleotide
      level. Hundreds of genes harboring mutations associated with genetic disease have
      now been identified by positional cloning. Using variation at closely linked
      genetic markers, it is possible to predict the times in the past at which
      particular mutations arose. Such studies suggest that many of the rare mutations
      underlying human genetic disorders are relatively young. Studies of variation at
      genetic markers linked to particular mutations can provide insights into human
      geographic history, and historical patterns of natural selection and disease,
      that are not available from other sources. We review two approaches for
      estimating allele age using variation at linked genetic markers. A phylogenetic
      approach aims to reconstruct the gene tree underlying a sample of chromosomes
      carrying a particular mutation, obtaining a "direct" estimate of allele age from
      the age of the root of this tree. A population genetic approach relies on models
      of demography, mutation, and/or recombination to estimate allele age without
      explicitly reconstructing the gene tree. Phylogenetic methods are best suited for
      studies of ancient mutations, while population genetic methods are better suited
      for studies of recent mutations. Methods that rely on recombination to infer the
      ages of alleles can be fine-tuned by choosing linked markers at optimal map
      distances to maximize the information available about allele age. A limitation of
      methods that rely on recombination is the frequent lack of a fine-scale linkage
      map. Maximum likelihood and Bayesian methods for estimating allele age that rely
      on intensive numerical computation are described, as well as "composite"
      likelihood and moment-based methods that lead to simple estimators. The former
      provide more accurate estimates (particularly for large samples of chromosomes)
      and should be employed if computationally practical.

PMID- 11462234
TI  - Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with
      non-syndromic autosomal recessive deafness.
AB  - Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was
      found to be responsible for two non-syndromic recessive deafness loci located on
      human chromosome 21q22.3, DFNB8 and DFNB10. We found evidence for linkage to the
      DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating
      congenital autosomal recessive sensorineural deafness. The audiometric tests
      showed a loss of hearing greater than 70 dB, in all affected individuals of both
      families. Mutation screening of TMPRSS3 revealed two novel missense mutations,
      W251C and P404L, altering highly conserved amino acids of the serine protease
      domain. Both mutations were not found in 200 control Tunisian chromosomes. The
      detection of naturally-occurring TMPRSS3 missense mutations in deafness families
      identifies functionally important amino acids. Comparative protein modeling of
      the TMPRSS3 protease domain predicted that W251C might lead to a structural
      rearrangement affecting the active site H257 and that P404L might alter the
      geometry of the active site loop and therefore affect the serine protease
      activity.

PMID- 11462235
TI  - Identification of novel RP2 mutations in a subset of X-linked retinitis
      pigmentosa families and prediction of new domains.
AB  - X-linked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity with
      almost five distinct loci on the X chromosome. So far, only two XLRP genes have
      been identified, RPGR (or RP3) and RP2, being mutated in approximately 70% and
      10% of the XLRP patients. Clinically there is no clearly significative difference
      between RP3 and RP2 phenotypes. In the attempt to assess the degree of
      involvement of the RP2 gene, we performed a complete mutation analysis in a
      cohort of patients and we identified five novel mutations in five different XLRP
      families. These mutations include three missense mutations, a splice site
      mutation, and a single base insertion, which, because of frameshift, anticipates
      a stop codon. Four mutations fall in RP2 exon 2 and one in exon 3. Evidence that
      such mutations are different from the 21 RP2 mutations described thus far
      suggests that a high mutation rate occurs at the RP2 locus, and that most
      mutations arise independently, without a founder effect. Our mutation analysis
      confirms the percentage of RP2 mutations detected so far in populations of
      different ethnic origin. In addition to novel mutations, we report here that a
      deeper sequence analysis of the RP2 product predicts, in addition to cofactor C
      homology domain, further putative functional domains, and that some novel
      mutations identify RP2 amino acid residues which are evolutionary conserved,
      hence possibly crucial to the RP2 function.

PMID- 11462236
TI  - Missense polymorphism in the human carboxypeptidase E gene alters enzymatic
      activity.
AB  - Carboxypeptidase E (CPE) is involved in the biosynthesis of peptide hormones and
      neurotransmitters, including insulin. One of the features of type 2 diabetes
      mellitus (T2DM) is an elevation in the proinsulin level and/or proinsulin/insulin
      molar ratio, suggesting that mutations in proinsulin processing enzymes may
      contribute to the development of T2DM. We scanned CPE for mutations in a
      collection of Ashkenazi T2DM families and identified five novel single nucleotide
      polymorphisms (SNPs). An SNP in the 283(rd) codon, c.847C>T, changes arginine to
      tryptophan (R283W). The residue Arg283 is conserved among CPE orthologs as well
      as most enzymatically active metallocarboxypeptidases. Of the 272 Ashkenazi T2DM
      pedigrees screened, we found four families segregating R283W. Within these four
      families, patients who inherited one copy of this variant had much earlier age of
      onset for T2DM. The R283W CPE protein cleaves peptide substrates with
      substantially lower efficiencies and is less stable at elevated temperature. In
      addition, the R283W CPE variant has a narrower pH optimum and is much less active
      at pH 6.0-6.5, indicating that the R283W CPE variant would be substantially less
      active than wild type CPE in the trans-Golgi network and immature secretory
      vesicles where the enzyme functions in vivo. To summarize, we uncovered a rare
      non-conservative missense mutation in CPE and demonstrated that the mutant
      protein has altered enzymatic properties. We predict that this mutant could cause
      hyperproinsulinism and diabetes in the homozygous state.

PMID- 11462237
TI  - DHPLC analysis of the MECP2 gene in Italian Rett patients.
AB  - Rett Syndrome (RTT) is an X-linked dominant neurodevelopmental disorder, which
      almost exclusively affects girls, with an estimated prevalence of one in 10,000
      15,000 female births. Mutations in the methyl CpG binding protein 2 gene (MECP2)
      have been identified in roughly 75% of classical Rett girls. The vast majority of
      Rett cases (99%) are sporadic in origin, and are due to de novo mutations. We
      collected DNA samples from 50 Italian classical Rett girls, and screened the
      MECP2 coding region for mutations by denaturing high-performance liquid
      chromatography (DHPLC) and subsequent direct sequencing. DHPLC is a recently
      developed method for mutation screening which identifies heteroduplexes formed in
      DNA samples containing mismatches between wild type and mutant DNA strands,
      combining high sensitivity, reduced cost per run, and high throughput. In our
      series, 19 different de novo MECP2 mutations, eight of which were previously
      unreported, were found in 35 out of 50 Rett girls (70%). Seven recurrent
      mutations were characterized in a total of 22 unrelated cases. Initial DHPLC
      screening allowed the identification of 17 out of 19 different mutations (90%);
      after optimal conditions were established, this figure increased to 100%, with
      all recurrent MECP2 mutations generating a characteristic chromatographic
      profile. Detailed clinical data were available for 27 out of 35 mutation carrying
      Rett girls. Milder disease was detectable in patients carrying nonsense mutation
      as compared to patients carrying missense mutations, although this difference was
      not statistically significant (P = 0.077).

PMID- 11462238
TI  - Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome.
AB  - Alport syndrome is a progressive renal disease leading to chronic renal failure,
      which often is accompanied by sensorineural deafness and ophthalmological signs
      in the form of anterior lenticonus. The X-linked form of the disease is caused by
      mutations in the COL4A5 gene encoding the alpha5-chain of type IV-collagen. We
      performed mutation analysis of the COL4A5 gene by PCR-SSCP analysis of each of
      the 51 exons with flanking intronic sequences in 81 patients suspected of X
      linked Alport syndrome including 29 clear X-linked cases, 37 cases from families
      with a pedigree compatible with X-linked inheritance, and 15 isolated cases. We
      found a mutation detection rate of 52% (42/81) (58% in males and 21% in females),
      and 69% (20/29) in families who clearly demonstrated X-linked inheritance. Thirty
      six different mutations were found in 42 patients comprising 16 missense
      mutations, seven frameshifts, three in-frame deletions, four nonsense mutations,
      and six splice site mutations. Twenty-two of the mutations have not previously
      been reported. Furthermore, we found one non-pathogenic amino acid substitution,
      one rare variant in a non-coding region, and one polymorphism with a
      heterozygosity of 28%. Three de novo mutations were found, two of which were
      paternal and one of maternal origin.

PMID- 11462239
TI  - Detection of germline mutations in the BRCA1 gene by RNA-based sequencing.
AB  - BRCA1 mutation detection is expensive and has sensitivity limitations, which
      might at least partially be overcome by RNA-based sequencing. There are claims
      that RNA tests are unreliable due to differential splicing, exon skipping, or
      nonsense-mediated mRNA decay that results in either the absence or low expression
      of mRNA harboring mutations. The major aim of this study was to determine if the
      application of specific high temperature annealing primers can assure high
      sensitivity of detection of BRCA1 sequence alterations by cDNA sequencing. The
      study group comprised 21 Polish cancer families with aggregations of breast
      and/or ovarian cancer. We detected mutations in 10 out of 21 unrelated patients.
      These were: nucleotide substitutions (c.309T>C; c.300T>G); nucleotide insertions
      (c.5382insC) three cases; nucleotide deletions (c.4154delA) one case, (c.
      185delAG) one case, (c.3819delGTAAA) two cases; and the deletion of the entire
      sequence of exon 22, one case. In addition, we identified three transcript
      variants resulting from alternative splice sites affecting the last six
      nucleotides of exon 1a (GTAAAG), and the first three nucleotides (CAG) of exon 8
      and exon 14. In all cases these were cDNA heterozygous changes. Two of these
      splice site changes have not been previously described. Sequencing of genomic DNA
      "exon by exon" did not result in the detection of any additional abnormalities.
      The sensitivity of our analyses was sufficient to reliably detect mutations
      without the necessity of tissue culturing to obtain enough template cDNA for
      analysis.

PMID- 11462240
TI  - A new PCR assay useful for screening of FRAXE/FMR2 mental impairment among males.
AB  - FRAXE (FMR2) is a fragile site associated with mental impairment located in Xq28,
      600 kb distal to FRAXA (FMR1), the fragile X syndrome fragile site. The FRAXE
      mutation is an expansion of a CCG repeat that results in methylation of a nearby
      CpG island. FRAXE alleles could be divided into four categories: normal (6-30 CCG
      repeats), intermediate (31-60 CCG repeats), premutation (61-200 CCG repeats), and
      full mutation (over 200 repeats). We have developed a non-isotopic polymerase
      chain reaction (PCR)-based assay for the identification of FRAXE full mutation
      alleles among mentally impaired men. In this novel PCR test for the FRAXE locus,
      we used three primers to permit an amplification of a 223 bp monomorphic internal
      control fragment in addition to the amplification of a 419 bp (CCG)(16) FRAXE
      locus band. A linear series of 93 male patients referred for FRAXE testing but
      found to be negative for the (CCG)(n) expansion in the FMR2 gene by Southern
      blotting analysis were retested by our PCR technique. In addition, we analyzed
      two positive controls consisting of a FRAXE fully mutated male and one male with
      a Xq terminal deletion. The developed PCR test showed accuracy of 100% in the
      normal individuals retested by PCR analysis, as well as in the two positive
      control samples utilized, in which the strategy of multiplex amplification worked
      as expected. Although not suitable for medical diagnosis of females and mosaics,
      it constitutes an important strategy for PCR typing and for FRAXE population
      screening.

PMID- 11462241
TI  - Characterization of 11 novel mutations in the X-linked chronic granulomatous
      disease (CYBB gene).
AB  - The most frequent form of chronic granulomatous disease (CGD) is caused by
      inactivation of the CYBB gene, which encodes the gp91-phox subunit of phagocyte
      NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen
      species and thus from eradicating bacterial and fungal infections. We
      investigated 16 unrelated male patients with suspected X-linked CGD and gp91-phox
      deficiency. A mutation was found in the CYBB gene of all 16 patients, and 11 of
      these mutations were novel. Eleven patients (69%) had a point mutation (84G>A in
      two unrelated patients, and 177C>G, 217C>T, 388C>T, 676C>T, 691C>T, 868C>T,
      919A>C, 1384G>T and T1514G in one case each, yielding W28X, C59W, R73X, R130X,
      R226X, Q231X, R290X, T307P, E462X, L505R gp-91phox). One patient had an in-frame
      deletion removing two amino acids (R54 and A55). Finally, insertions or
      duplications were found in four patients (from +1 to +31 bases). Overall, 12
      (75%) of the mutations led to the production of a truncated protein. No clear
      correlation was found between clinical manifestations and genomic/biochemical
      alterations. Thirteen mothers could be tested, and all were carriers. Hum Mutat
      18:163, 2001.

PMID- 11462242
TI  - Evidence of a founder mutation of BRCA1 in a highly homogeneous population from
      southern Italy with breast/ovarian cancer.
AB  - Several genes have been involved in the pathogenesis of hereditary breast/ovarian
      cancer (BOC), but mutations in the BRCA1 gene are by far the most recurrent. In
      this study, we report the identification of a founder mutation in a
      geographically and historically homogeneous population from Calabria, a south
      Italian region. A screening performed on 24 patients from unrelated families
      highlighted the high prevalence of a 5083del19 alteration in the BRCA1 gene,
      which accounts for 33% of the overall gene mutations. The same mutation was also
      detected in 4 patients, all of Calabrian origin, referred to us by research
      centres from the north of Italy. Allelotype analysis, performed on probands and
      unaffected family members revealed the presence a common allele, therefore
      suggesting a founder effect due to a common ancestor. Our findings underscore the
      importance of ethnic background homogeneity in patients' selection and highlight
      the usefulness of founder mutations as a potential tool for optimisation of
      preclinical diagnosis in gene carriers and therapeutic approaches in affected
      individuals.

PMID- 11462243
TI  - Four novel mutations in the RPE65 gene in patients with Leber congenital
      amaurosis.
AB  - Leber congenital amaurosis (LCArpar; is a heterogeneous disorder representing the
      congenital forms of retinitis pigmentosa accounting for about 5% of all retinal
      dystrophies. The RPE65 gene product is required for regeneration of the visual
      pigment for phototransduction. Defects in the RPE65 gene have so far been shown
      to account for approximately 10 % of known cases of LCA. Here we describe four
      additional novel mutations in the RPE65 gene (c.889delA, c.131G>A, c.1249G>C,
      c.430T>G) and several novel polymorphisms in a large series of LCA patients. Hum
      Mutat 18:164, 2001.

PMID- 11462244
TI  - Molecular analysis of 40 Italian patients with mucopolysaccharidosis type II: New
      mutations in the iduronate-2-sulfatase (IDS) gene.
AB  - Mucopolysaccharidosis type II (MPS2, or Hunter syndrome), rare X-linked lysosomal
      storage disorder, results from deleterious mutations in the iduronate-2-sulfatase
      (IDS) gene. We report here the mutational analysis of a total of 40 unrelated
      Italian MPS II patients ranging from mild to severe phenotype. We are able to
      assign the genotype to 29 of them (72.5%), identifying 22 different mutations,
      five of which are unpublished (c.533delTT, W12X, N265I, c.1131-1142del, c.1131
      1305del). A total of 55.2% of the molecularly characterised patients resulted
      from missense mutations, 20.7% from nonsense mutations, and another 13.8% of
      patients from small deletions (<20pb) or splice mutations, whereas 10.3% of the
      cases carried major structural alterations such as large deletion and
      rearrangements. The results reported here support the evidence of the mutational
      heterogeneity of the IDS gene as well as the difficulty to correlate genotype and
      phenotype in the patients with MPSII. However, the molecular characterisation of
      the patients is advantageous, making the carrier detection feasible for the
      females in the family at risk and improving the reliability of prenatal diagnosis
      techniques. Moreover, it provides a good foundation for therapeutic strategies.

PMID- 11462245
TI  - Expression and analysis of CLN2 variants in CHO cells: Q100R represents a
      polymorphism, and G389E and R447H represent loss-of-function mutations.
AB  - Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal hereditary
      childhood disease. The gene underlying LINCL, CLN2, encodes a lysosomal enzyme,
      tripeptidyl peptidase I (TPP-I), deficiency in which leads to lysosomal
      accumulation of autofluorescent materials accompanied by severe neuronal atrophy.
      Mutational analysis was conducted to characterize different CLN2 alleles. Two
      probands of Romany origin were found to be homozygous for an allele that encoded
      a protein with two changes, designated Q100R+G389E CLN2. To distinguish potential
      polymorphisms from mutations, a recombinant expression system was used to
      investigate individual constructs. Elevated levels of TPP-I activity in CHO cells
      expressing Q100R CLN2 and background activity in CHO cells expressing G389E CLN2
      clearly defines G389E as a pathogenic mutation and indicates that Q100R is a
      polymorphism. Association of the R447H mutation with a delayed onset form of
      LINCL in two separate families raised the question of whether R447H CLN2 retains
      residual activity. However, CHO cells expressing R447H CLN2 had TPP-I activity
      comparable to that of neo transfected cells, indicating that any residual
      activity was below the level of detection in this experimental system. Hum Mutat
      18:165, 2001.

PMID- 11462246
TI  - Identification of recurrent and novel mutations in the LDL receptor gene in
      German patients with familial hypercholesterolemia.
AB  - In order to identify mutations in the low density lipoprotein receptor (LDLR)
      gene in primary hypercholesterolemia, we screened 100 unrelated German
      individuals with elevated plasma LDL-C (LDL-C > 4,7 mmol/l) for mutations in the
      18 exons and their flanking intronic sequences including the promoter region of
      the LDL-R gene using a combination of polymerase chain reaction (PCR), denaturing
      gradient gel electrophoresis (DGGE) and direct sequencing. In addition we tested
      all patients for the presence of mutations in codons 3456 - 3553 of the gene
      encoding apolipoprotein B-100. In 56 individuals we detected 37 different
      mutations affecting the LDL-R gene, 16 of which, designated C122R, C127Y, C163W,
      F179L, R236W, E296X, R553C, V618D, T721I, V785D, G1358+2A, 257delTCTGGAGGT,
      657delC, 676insACGGTATGGACTGCAdelGACG, C1205delTCT, 2420delTCCTTCT, have not yet
      been reported. One proband was a compound heterozygote showing two separate
      sequence variations (E207X and T705I). Seven patients were heterozygous for the
      mutation R3500Q within the apoB-100 gene. These results demonstrate that there is
      a broad spectrum of mutations in the LDL-R gene and that the R3500Q mutation is a
      frequent cause of hypercholesterolemia in the German population.

PMID- 11462247
TI  - Analysis of the entire coding region of the cystic fibrosis transmembrane
      regulator gene in idiopathic pancreatitis.
AB  - Many Cystic Fibrosis (CF) carriers have been detected testing some subjects with
      chronic pancreatitis for a limited number of mutations. The aim of this study was
      to find out if some subjects with pancreatitis and a CFTR mutation actually carry
      another, undetected mutation. We screened for 18 CFTR mutations plus the CFTR
      intron 8 poly(T) tract length a population of 67 patients suffering from
      idiopathic either acute, or recurrent acute, or chronic pancreatitis. Three of
      them were diagnosed as affected by CF. Among the others, a subset of 14 (8 CFTR
      mutation carriers, 4 5T carriers, and 2 sweat chloride borderliners) was selected
      and analyzed by denaturing gradient gel electrophoresis. Six possibly CF-related
      mutations were detected: L997F and 3878delG were found in two of the subjects
      already carrying another mutation, S1235R and L997F in one patient carrying the
      5T, and L997F and D614G in the two patients with borderline sweat chloride. Among
      the 14 selected cases a total of 11 patients carried at least one mutation, and
      three of them were compound heterozygotes. Though it is debatable whether these
      three individuals can be considered affected by CF, their pancreatitis is
      possibly a clinical manifestation of some CFTR-related disease. Hum Mutat 18:166,
      2001.

PMID- 11462248
TI  - Population screening of F508del (DeltaF508), the most frequent mutation in the
      CFTR gene associated with cystic fibrosis in Argentina.
AB  - Cystic fibrosis (CF) is the most common autosomal recessive disease in the
      Caucasian population. The disease can be caused by one of the more than 900
      different mutations in the Cystic Fibrosis Transmembrane Conductance Regulator
      (CFTR) gene. However, the deletion of the phe508-codon is the most prevalent
      mutation observed. Our aim was to perform a screening for this mutation
      (DeltaF508, or F508del) in the population of Mendoza, Argentina. For the
      screening, 1,000 blood samples were obtained from CF asymptomatic individuals and
      combined into 100 pools each containing 10 different blood samples. Pools
      containing at least one F508del carrier were detected by heteroduplex formation
      during the PCR amplification of exon 10. The PCR was designed to introduce a
      recognition site for a restriction enzyme that confirmed the presence of the
      deletion F508del in the positive pools. The results with this simple method
      indicate a frequency of carriers in the Mendoza population of 2.1% (1.3%-3.2, 95%
      confidence limits). The observed frequency of carriers is similar to that
      reported for European populations. Hum Mutat 18:167, 2001.

PMID- 11462271
TI  - [No one should suffer because of "cervical cytology". Screening programs should
      be revised in each county].

PMID- 11462272
TI  - [Genetic breakthrough in inflammatory bowel disease].

PMID- 11462273
TI  - [Of what significance is abnormal result of smear test? Anxiety because of
      insufficient information in connection with abnormal result of cervical smear
      test].
AB  - The purpose of the study was to investigate possible differences in psychological
      response between two groups of women after pathological cervical smear tests (CIN
      I or recurrent CIN I and/or CIN II-III respectively). 43 women participated. A
      standardised questionnaire was used. In 75 percent of the cases the result was
      given over the telephone. The number of women who reacted with medium to strong
      anxiety in the CIN I group (15/22) did not differ from those in the group with
      CIN II-III (15/21). 45 percent of the women in the CIN I group thought their
      lesions to be malignant. 64 percent of the women in the CIN I group, as compared
      to 38 percent of the women in the CIN II-III group, benefitted from the
      additional information they asked for and received. A majority of the women would
      have liked more information as well as the opportunity to discuss the findings in
      a more personal way.

PMID- 11462274
TI  - [Presbyacusis--hearing loss in old age].
AB  - Presbyacusis is a very common type of hearing loss, often having profound effects
      on the quality of life in old age. Since the number of elderly persons is
      increasing, the incidence of presbyacusis is also expected to increase in the
      future. Presbyacusis is caused by cochlear degeneration, most pronounced in the
      basal cochlear coil. The most common audiometric configuration is a gently
      sloping audiogram, above all affecting the high frequencies. Efforts to improve
      auditory communication in old age are important, and can be expected to result in
      improved quality of life for elderly persons and in more efficient use of public
      resources. The alleviation of age-related hearing handicap includes aural
      rehabilitation with hearing aid fitting and training programs, specially designed
      for elderly people. Hearing loss is often combined with other handicaps, such as
      dementia, immobility and poor vision. The synergistic effects of multiple
      handicaps can be extensive. Prevention is an issue which is both challenging and
      problematic. The most important preventive measure is noise reduction, which must
      start early in life and not shortly before retirement. Inner ear treatment
      programs, currently under development, might possibly be suitable for treatment
      of inner ear disorders in the future. Considerable gains can be achieved with
      respect to resources both human and economical through rehabilitation and
      suitable preventive measures.

PMID- 11462275
TI  - [Residential care after the geriatric care reform. District nurses experience
      extensive responsibility and limited rights].
AB  - We studied the care of patients in homes for the elderly and in special homes for
      the demented in the city of Malmo. Nine district nurses were interviewed using a
      tape recorder, and the content of the interviews was analyzed. Many patients
      needed extensive care, and resources were insufficient regarding both number of
      staff and their competence. The management of nursing in the various districts of
      the city was not well-defined. More consulting time was requested on the part of
      both district nurses and general practitioners in homes for the elderly and homes
      for the demented.

PMID- 11462276
TI  - [Three future perspectives of health information. Information can make the public
      independent, demanding or well-informed].

PMID- 11462277
TI  - [Interest for more health information. Information given by health authorities
      and family is considered more reliable than information found on the Internet,
      based on a study in the county of Ostergotland].

PMID- 11462278
TI  - [Placental abruption. Hypovolemia can explain difficulties when attempting
      resuscitation in asphyxia].

PMID- 11462279
TI  - [Congress in the USA on hot topics in neonatology. Unnecessary, sometimes harmful
      methods are still used].

PMID- 11462280
TI  - [New classification of diagnoses from the SFAM Informatik].

PMID- 11462281
TI  - [Can breast milk protect against cardiovascular disease by blood pressure
      programming?].

PMID- 11462282
TI  - [National targets for public health. Focusing on factors of social environment].

PMID- 11462283
TI  - [Organizational stress and care of individuals with professional burnout].

PMID- 11462284
TI  - [Is the "inside of human beings" responsibility of health care services?].

PMID- 11462285
TI  - [Norwegian and Swedish health care--different conditions, same problems].

PMID- 11462286
TI  - [The 20-points orthopedics course is based on scientific basis].

PMID- 11462287
TI  - Transcranial Doppler pulsatility indices as a measure of diffuse small-vessel
      disease.
AB  - BACKGROUND AND PURPOSE: Elevation in pulsatility indices (PIs) as measured by
      transcranial Doppler (TCD) have been postulated to reflect downstream increased
      vascular resistance caused by small-vessel ischemic disease. METHODS: The authors
      retrospectively compared TCD PIs and magnetic resonance imaging (MRI)
      manifestations of small-vessel disease in 55 consecutive patients who underwent
      TCD studies and brain MRI within 6 months of each other during a 2-year period.
      RESULTS: Correlations between TCD middle cerebral artery PIs and MRI measures
      were as follows: periventricular hyperintensity (PVH) = 0.52 (P < .0001), deep
      white matter hyperintensity (DWMH) = 0.54 (P < .0001), lacunar disease = 0.31 (P
      = .02), and combined PVH/DWMH/lacunes = 0.54 (P < .0001). Correlation between
      pontine ischemia and vertebrobasilar PIs was 0.46 (P = .0004). Univariate
      analysis showed that age, elevated PI, and hypertension strongly correlated with
      white matter disease measures. After adjusting for these factors in a
      multivariate Poisson regression analysis, PI remained an independent predictor of
      white matter disease. Receiver operator curve analyses identified PI cut points
      that allowed discrimination of PVH with 89% sensitivity and 86% specificity and
      discrimination of DWMH with 70% sensitivity and 73% specificity. CONCLUSIONS:
      Elevation in PIs as measured by TCD shows strong correlation with MRI evidence of
      small-vessel disease. TCD may be a useful physiologic index of the presence and
      severity of diffuse small-vessel disease.

PMID- 11462288
TI  - A broad diagnostic battery for bedside transcranial Doppler to detect flow
      changes with internal carotid artery stenosis or occlusion.
AB  - BACKGROUND AND PURPOSE: The authors establish accuracy parameters of a broad
      diagnostic battery for bedside transcranial Doppler (TCD) to detect flow changes
      due to internal carotid artery (ICA) stenosis or occlusion. METHODS: The authors
      prospectively studied consecutive patients with stroke or transient ischemic
      attack referred for TCD. TCD was performed and interpreted at bedside using a
      standard insonation protocol. A broad diagnostic battery included major criteria:
      collateral flow signals, abnormal siphon or terminal carotid signals, and delayed
      systolic flow acceleration in the middle cerebral artery. Minor criteria included
      a unilateral decrease in pulsatility index (< or = 0.6 or < or = 70% of
      contralateral side), flow diversion signs, and compensatory velocity increase.
      Angiography or carotid duplex ultrasound (CDU) was used to grade the degree of
      carotid stenosis using North American criteria. Sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of TCD
      findings were determined. RESULTS: Seven hundred and twenty patients underwent
      TCD, of whom 517 (256 men and 261 women) had angiography and/or CDU within 8.8 +/
      0.9 days. Age was 63.1 +/- 15.7 years. For a 70% to 99% carotid stenosis or
      occlusion, TCD had sensitivity of 79.4%, specificity of 86.2%, PPV of 57.0%, NPV
      of 94.8%, and accuracy of 84.7%. For a 50% to 99% carotid stenosis or occlusion,
      TCD had sensitivity of 67.5%, specificity of 83.9%, PPV of 54.5%, NPV of 90.0%,
      and accuracy of 81.6%. TCD detected intracranial carotid lesions with 84.9%
      accuracy and extracranial carotid lesions with 84.4% accuracy (sensitivity of 88%
      and 79%, specificity of 85% and 86%, PPV of 24% and 54%, and NPV of 99% and 95%,
      respectively). The prevalence of the ophthalmic artery flow reversal was 36.4% in
      patients with > or = 70% stenosis or occlusion. If present, this finding
      indicated a proximal ICA lesion location in 97% of these patients. CONCLUSIONS:
      In symptomatic patients, bedside TCD can accurately detect flow changes
      consistent with hemodynamically significant ICA obstruction; however, TCD should
      not be a substitute for direct carotid evaluation. Because TCD is sensitive and
      specific for a > or = 70% carotid stenosis or occlusion in both extracranial and
      intracranial carotid segments, it can be used as a complementary test to refine
      other imaging findings and detect tandem lesions.

PMID- 11462289
TI  - Magnetic resonance analysis of postsurgical temporal lobectomy.
AB  - BACKGROUND AND PURPOSE: The effect of temporal lobe transection area, volume of
      postoperative gliosis, and surgical technique on patients' seizure-free outcome
      is unknown. The authors studied the effects of these variables on patients'
      seizure-free outcome. METHODS: A retrospective review of magnetic resonance
      imaging examinations acquired 3 to 18 months after temporal lobe resection was
      carried out for 18 patients with intractable temporal lobe seizures and known
      postsurgical outcomes for more than 2 years. The total volume of radiologically
      probable gliosis evident on axial proton-density-weighted images was calculated
      for each patient using software on an independent console. The total area of
      temporal lobe surface transected by the scalpel was calculated as well, using
      sagittal T1-weighted images. The total volume of gliosis, the total area of
      transected temporal lobe, and the specific type of surgery (sparing vs no sparing
      of the superior temporal gyrus) were then correlated with the postsurgical
      outcome of the patients. An examiner with no prior knowledge of the patients'
      postsurgical outcomes carried out the above calculations and measurements. The
      patients' postoperative outcome was defined using Engel classifications, and
      patients were divided into 2 groups: group A with Engel class 1 (n = 9) and group
      B with Engel classes 2-4 (n = 9). RESULTS: The mean volumes of postoperative
      gliosis were not significantly different between group A (3592.3 mm3) and group B
      (4270 mm3). The mean area of transected temporal lobe was also similar between
      group A (1865.2 mm2) and group B (1930 mm2). With regard to surgical technique,
      there were 5 patients who had the superior temporal gyrus resected and 13 who did
      not. Eighty percent of patients with the superior temporal gyrus resected were
      Engel class 1 or 2, whereas only 20% were of Engel class 3 or 4. CONCLUSIONS: The
      authors found no clear association between postoperative outcome and residual
      temporal lobe gliosis, the surgical technique, or the total area of temporal lobe
      transected by the scalpel.

PMID- 11462290
TI  - Intravascular ultrasound Doppler measurement of blood flow velocity.
AB  - BACKGROUND AND PURPOSE: The authors investigated the feasibility and accuracy of
      intravascular Doppler sonography (IVDS) with a newly developed microprobe.
      METHODS: The known method to determine blood flow velocity by transcutaneous
      Doppler sonography was transferred to an intravascular usable Doppler probe. With
      the improved technique, a microprobe measuring 0.3 mm in diameter can be advanced
      through a 5F catheter used in routine diagnostic angiography to perform
      intravascular Doppler sonography. In a first step, the conditions for application
      and measurement were studied in a flow tube model and were transferred in a
      second step to patients undergoing routine angiography and patients with arterial
      stenoses. RESULTS: Measurements with nondegassed liquids showed a high intensive
      acoustic signal, but no echo effect could be recorded in degassed liquids. IVDS
      of healthy vessels in 40 patients showed the same typical flow pulse curve as
      seen in transcutaneous measurements. The optimal position of the microprobe with
      respect to the contact of the vessel wall, the diastolic and systolic phase, and
      the distance to the tip of the catheter could be evaluated. In 95.6% of the 40
      patients with healthy vessels, IVDS was successful. Fourteen patients with
      arterial stenotic diseases were investigated before and after percutaneous
      transluminal angioplasty, and the results of these investigations correlated well
      with the angiographical results. CONCLUSIONS: For percutaneously directly
      reachable vessels, the transcutaneous Doppler sonography is the choice for easy
      noninvasive and inexpensive measurement of blood flow velocity. However, for
      vessels that are difficult or impossible to reach percutaneously, intravascular
      measurement is a valid procedure.

PMID- 11462291
TI  - Single photon emission computed tomography, magnetic resonance imaging
      hyperintensity, and cognitive impairments in patients with vascular dementia.
AB  - BACKGROUND: The relationship between subcortical hyperintensity (SH) on magnetic
      resonance imaging (MRI), cortical perfusion on single photon emission computed
      tomography (SPECT), and cognitive function is not well understood. The authors
      examined these relationships in individuals with vascular dementia (VaD), paying
      particular attention to frontal lobe function to determine whether the presence
      of SH on MRI was associated with frontal hypoperfusion on SPECT, which in turn
      would be associated with impairments of executive-attention function. METHODS:
      Patients with vascular dementia (n = 26) were assessed on neurocognitive tests
      and brain MRI and SPECT. SH volume was quantified from the axial T2-weighted
      fluid attenuated inversion recovery MRI. Total counts of activation across voxels
      for 12 cortical regions of interest were determined from SPECT. Perfusion ratios
      of both total cortical and frontal activation relative to cerebellum activation
      were derived, and regression analyses were performed to determine the
      relationships between cognitive, MRI, and SPECT indices. RESULTS: SH volume on
      MRI was significantly associated with frontal lobe perfusion, but not with global
      cortical perfusion as measured by SPECT. Frontal lobe perfusion did not
      consistently correlate with performance on measures of executive-attention
      function, although both total and frontal perfusion ratios were significantly
      associated with other cognitive functions. CONCLUSIONS: These results suggest
      that a functional "disconnection" between the frontal lobes and subcortical
      structures does not fully account for the magnitude of global cognitive
      impairment in VaD. Cortical perfusion as measured by SPECT appears to be
      associated with cognitive performance, but not specifically executive-attention
      dysfunction. Additional studies are needed to further examine the relationship
      between subcortical and cortical function in VaD.

PMID- 11462292
TI  - SonoVue in transcranial Doppler investigations of the cerebral arteries.
AB  - BACKGROUND AND PURPOSE: The authors investigated the safety and diagnostic
      potential of a new ultrasound contrast agent (SonoVue) using transcranial color
      coded duplex sonography (TCCS). METHODS: Forty patients were enrolled in a
      multicenter, open-label (on-site), blind (off-site), randomized, dose-ranging
      crossover study. SonoVue was administered as an intravenous bolus injection of 4
      different dosages (0.3, 0.6, 1.2, and 2.4 mL). Efficacy was evaluated as (1) off
      site assessment of global quality of the Doppler investigation (based on color or
      power Doppler images and spectral analysis) at baseline and following each dose
      of SonoVue according to a 4-point scale (from very poor to excellent imaging of
      blood flow) and (2) duration of clinically useful signal enhancement and color or
      power Doppler visualization of blood flow. Additional on-site efficacy
      assessments performed following each dose of SonoVue included confidence in
      diagnosis and global consequences of contrast enhancement on diagnosis. Safety
      evaluations included clinical laboratory tests, neurological examination,
      injection site tolerability, and incidence of adverse events and their
      relationship to the study agent. RESULTS: All doses of SonoVue significantly
      improved the global quality of Doppler examinations (P < .05). The median
      duration of clinically useful enhancement was dose related (P < .001) and ranged
      from 2 to 6 minutes at the highest dose. The administration of the contrast agent
      changed a nondiagnostic study to a diagnostic one in 66% of patients and
      increased the confidence in diagnosis in 74% of cases. No serious adverse events
      were recorded following SonoVue administration. The observed adverse reactions
      were all transient and mild in intensity. CONCLUSIONS: The results obtained from
      this multicenter study demonstrate that the administration of SonoVue to patients
      with ischemic cerebrovascular disease who undergo TCCS examination of cerebral
      vessels improves the visualization of intracranial arteries, providing a dose
      dependent contrast enhancement and a clinically useful duration of signal
      enhancement related to the dose. During this multicenter study, SonoVue proved to
      be a safe and well-tolerated compound.

PMID- 11462293
TI  - A computed tomography score for assessment of mass effect in space-occupying
      cerebellar infarction.
AB  - BACKGROUND AND PURPOSE: Patients with cerebellar infarction are threatened by
      infratentorial herniation and impaired circulation of cerebrospinal fluid if mass
      effect in posterior fossa develops. Clinical assessment is often impaired in
      patients with disturbances of consciousness. Therefore, computed tomography (CT)
      examination is essential in the diagnosis of complication and decision for
      operative treatment. METHODS: Mass effect of cerebellar infarction was
      quantitatively assessed using a 3-item CT score: width of fourth ventricle,
      compression of quadrigeminal cistern, and width of lateral ventricle. Retest and
      interrater reliability was determined. Validity of assessment of mass effect was
      examined using 185 CT scans from a cerebellar infarction study, and the effect of
      operative treatment on CT score was determined. RESULTS: The correlation
      coefficients for retest and interrater reliability were 0.94 and 0.75,
      respectively. The authors found a significant difference for the CT sum score and
      all CT items except "compression of the fourth ventricle" between patients with
      different levels of consciousness. Effect of operative treatment was documented
      by improvement of CT score. CONCLUSIONS: The proposed CT score is of high
      interrater and retest reliability, supplements the clinical assessment of the
      patient, and is able to monitor the efficacy of decompressive treatment.

PMID- 11462294
TI  - Effect of adenosine on cerebral blood flow velocity.
AB  - BACKGROUND AND PURPOSE: Evidence suggests that adenosine (ADN) is a potent
      vasodilator of cerebral vessels. However, the feasibility of manipulating human
      cerebral vascular resistance with ADN has not been assessed by means of TCD. The
      purpose of this study was to quantitatively estimate the change in middle
      cerebral artery cerebral blood flow velocity (CBFV) in response to intravenous
      ADN infusion in humans. METHODS: Eleven patients with subacute cerebrovascular
      events (ischemic stroke, transient ischemic attack, or hemorrhage) undergoing
      adenosine-thallium stress testing were studied before, during, and after ADN
      infusion to evaluate the effect of ADN on cerebral blood flow velocity.
      Continuous blood pressure (BP), heart rate (HR), respiration rate (RR), end-tidal
      CO2 (ET-CO2), and transcranial Doppler ultrasonography monitoring of CBFV and
      pulsatility index (PI) in both middle cerebral arteries were performed. RESULTS:
      The mean CBFVs were 65.4 +/- 19.2 cm/s before, 55.4 +/- 18.1 cm/s during, and
      64.1 +/- 22.5 cm/s after ADN infusion, which represents a statistically
      significant decrease during ADN test compared with both baseline (P = .007) and
      posttest levels (P = .017). The PI was increased during the test (0.91 +/- 0.2)
      when compared with baseline (0.71 +/- 0.1) (P = .007). During ADN injection, mean
      HR increased (P = .004) and mean ET-CO2 levels decreased significantly (P =
      .003). Mean BP and RR did not change significantly. CONCLUSIONS: The authors
      hypothesize that any direct vasodilatory effect of ADN on the distal cerebral
      peripheral vasculature may be negated by an effect of ADN on depth of respiration
      resulting in hypocapnia and secondary distal vasoconstriction.

PMID- 11462295
TI  - Helical high-resolution volume-rendered 3-dimensional computer tomography
      angiography in the detection of intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: This study was carried out to determine whether high
      resolution 3-dimensional prospective-volume-rendered computed tomographic (CT)
      angiography can replace conventional intra-arterial digital subtractional
      angiography in the diagnostic evaluation of patients with an acute subarachnoid
      hemorrhage (SAH) due to ruptured intracranial aneurysm. METHODS: Both techniques
      were performed in 30 consecutive patients within 2 to 12 hours after their
      admission to the hospital. RESULTS: In this group of 30 patients, CT angiography
      with 3-dimensional volume-rendered reconstruction detected 31 aneurysms in 25
      patients. Two aneurysms were missed on CT angiography. Conventional angiography
      detected 33 aneurysms in 27 patients. The authors considered angiograms in 3
      patients presenting with SAH as normal. In all cases where an aneurysm was
      detected on CT angiography, the finding was confirmed by conventional
      angiography. CONCLUSIONS: CT angiography with 3-dimensional post-processing is a
      sensitive, noninvasive method that provides a 3-dimensional view of intracranial
      vessels and the aneurysm. It is also very useful in planning either surgical or
      endovascular treatment.

PMID- 11462296
TI  - Transcranial sonography of brain tumors in the adult: an in vitro and in vivo
      study.
AB  - BACKGROUND: Few reports indicate the potential of transcranial sonography (TCS)
      in detecting human brain tumors. METHODS: With an Agilent Sonos 2500 ultrasound
      device, the authors studied 4 brain tumor phantoms and compared the findings with
      magnetic resonance imaging (MRI). TCS was performed on 40 patients with
      intracranial tumors in a follow-up design. Sonographic tumor volume and affection
      of the ventricular system were compared with MRI findings. RESULTS: The authors
      found a good correlation between TCS and MRI volumetry in the in vitro study. TCS
      showed good intraobserver and interobserver reliability. A new volumetric formula
      for TCS measurement was determined. TCS detection rate of brain tumors in vivo
      was 40%. When the investigators were given access to radiological findings, the
      rate of tumor identification was 80%. Despite a sufficient acoustic window, 40%
      of gliomas grade II and III were not detected. One glioblastoma was not
      identified owing to an insufficient temporal acoustic window. Tumor volumes
      measured with MRI and TCS correlated well. MRI volumes exceeded TCS volumes by
      41%. In the postoperative examinations (mean = 8 days postoperative, n = 15), the
      resection cavity was displayed as hyperechogenic. It appeared impossible to
      differentiate between residual tumor tissue and normal repair mechanisms or
      blood. In the follow-up examination (mean = 99 days postoperative, n = 15) in 5
      patients, neither MRI nor TCS showed tumor regrowth. Ten patients had residual
      tumors that were detected by sonography. CONCLUSIONS: The value of TCS for the
      diagnostics of brain tumors is at present limited. Once the tumor has been
      identified, sonographic results match well with those of MRI.

PMID- 11462297
TI  - 1H spectroscopy in patients with amyotrophic lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: The authors investigate changes in brain metabolites
      among patients with amyotrophic lateral sclerosis (ALS). Twelve patients
      diagnosed with definite ALS (and 2 subgroups with either pronounced upper
      motoneuron signs or less obvious, probable upper motoneuron involvement) and 10
      controls were examined. 1H studies were performed on a 1.5-T Siemens Magnetom
      Vision with single voxel (SV). A voxel (TR = 1500 ms, TE = 270 ms, 512
      acquisitions, VOI = 8 cm3) was placed bilaterally in the precentral gyrus. In
      addition, chemical shift imaging (CSI) (VOI = 1 x 1 x 1.5 cm, TR = 1500 ms, TE =
      135 ms) was performed. Ratios of peak integrals (N-acetyl-aspartate/choline, N
      acetyl-aspartate/creatine, and creatine/choline) were determined. A Mann-Whitney
      U Test and a Wilcoxon Matched Pairs Test were applied. METHODS: The statistical
      analysis failed to demonstrate any significant differences between the ALS
      patients and the controls with respect to ratio measures. Using CSI, it was found
      that patients with clinically pronounced upper motoneuron signs had significantly
      lower (P = .037) N-acetyl-aspartate/choline ratios in the more affected
      hemisphere. CONCLUSIONS: The authors conclude that CSI is more effective at
      detecting lower N-acetyl-aspartate/choline levels among ALS patients than is SV.

PMID- 11462298
TI  - Pharmacokinetics of echocontrast agent infusion in a dog model.
AB  - Ultrasound contrast agents (UCAs) have a distinct diagnostic impact on
      transcranial Doppler (TCD) and duplex sonography. In addition to the properties
      of the UCA and ultrasound imaging modes, the duration of contrast enhancement
      depends on the administration mode. Infusion of UCAs may be appropriate for
      prolonging the diagnostically useful time of elevated Doppler intensity. Five
      sedated dogs were investigated by TCD during infusion with SonoVue, a new UCA
      consisting of sulfur hexafluoride microbubbles. The infusion rate was varied, and
      the time-intensity curves were analyzed. Infusion rate of 70 ml/h provided a
      stable mean level of increased Doppler intensity up to 24 to 26 dB over baseline,
      whereas a rate of 35 ml/h did not result in a stable plateau (range 8-19 dB over
      baseline [5 minutes after starting time]). The maximum increases in Doppler mean
      intensity (18.2 dB [35 ml/h] and 25.6 dB [70 ml/h]) were significantly different
      (P = .025). Pharmacokinetic analysis of SonoVue during inflow (by exponential
      functional fitting of the time-mean intensity curves) and elimination (by linear
      regression analysis) revealed no dose-related differences. This study
      demonstrated a dose-dependent level of increased Doppler mean intensity within
      the brain circulation during infusion of SonoVue. Unlike the bell-shaped course
      of Doppler signal enhancement seen after bolus injection, infusion generates a
      stable plateau, which is an important prerequisite for more advanced contrast
      applications.

PMID- 11462299
TI  - Selective arterial distribution of cerebral hyperperfusion in Fabry disease.
AB  - Fabry disease is an X-linked recessive deficiency of lysosomal alpha
      galactosidase A associated with an increased risk of early onset cerebrovascular
      disease. The disorder is reported to affect the posterior circulation
      predominantly. This hypothesis was investigated directly by the measurement of
      regional cerebral blood flow with positron emission tomography (PET). Resting
      regional cerebral blood flow (rCBF) in 26 hemizygous patients with Fabry disease
      and 10 control participants was examined using H(2)15O and PET. Statistical
      parametric mapping (SPM(t), SPM99) and PET images of patients and controls were
      produced. Significantly increased SPM(t) clusters were then color coded and
      blended with a coregistered T1 magnetic resonance imaging (MRI) template.
      Cerebral arterial territory maps were digitized and rescaled. Custom OpenGL and
      ImageVision Library C++ code was written to allow a first-order affine
      transformation of the blended SPM(t) and MRI template onto the arterial territory
      map. The affine transformation was constrained by choosing corresponding cerebral
      landmark "tie points" between the SPM(t) [symbol: see text] MRI template images
      and the cerebral arterial territory maps. The data demonstrated that the
      posterior circulation is the predominant arterial territory with a significantly
      increased rCBF in Fabry disease. No arterial distribution had a decreased rCBF.

PMID- 11462300
TI  - Human brain temperature in vivo: lack of heating during color transcranial
      Doppler ultrasonography.
AB  - This study was undertaken to assess the effect of ultrasound on human brain
      temperature in vivo. The investigation consisted of direct recording of
      intracranial temperature during color transcranial Doppler (TCD) sonography in a
      neurosurgical patient. The temperature was recorded from 3 thermocouples. One was
      implanted together with an intracranial pressure sensor into a surgically reduced
      intraparenchymal hematoma, the second was placed within the subdural space close
      to the temporal acoustic window, and the third was located extracranially at the
      outer surface of the temporal bone. Tympanic temperatures were also measured to
      give an approximation of global brain temperature. A 2.5-MHz transducer was used,
      and the system settings were as follows: spatial peak temporal average intensity
      = 234 mW/cm2 in B-mode at a maximum power of 32.3 mW and 2132 mW/cm2 in Doppler
      mode at a maximum power of 149.3 mW. Neither increase in the intraparenchymal
      brain temperature nor increase in the temperature at the bone/soft tissue
      interface was observed during 30 minutes of insonation. The ipsilateral tympanic
      temperature increased by only 0.06 degree C, and this value may be regarded as a
      measure of the overall increase in brain temperature. Passive cooling effect
      produced by the transducer, which was at ambient temperature, was found to reach
      the brain surface and to surpass any possible heating caused by the ultrasound.
      The results indicate that no noticeable increases in human brain temperature
      occur in response to ultrasound emitted by a color TCD device at high transmitter
      power settings within the diagnostic range.

PMID- 11462301
TI  - Does reversal of ischemia on diffusion-weighted imaging reflect higher apparent
      diffusion coefficient values?
AB  - This study investigated whether ischemia on diffusion-weighted imaging (DWI) that
      reverses has higher apparent diffusion coefficients (ADCs). A patient treated
      with thrombolytics was evaluated with serial magnetic resonance imaging studies
      before treatment, at 3 and 14 days and at 4 weeks. A 100.01-cm3 left
      frontoparietal stroke on baseline DWI was only 18.11 cm3 (18%) on 4-week fluid
      attenuated inversion recovery. The mean ADC was 7.43 x 10(-3) mm2/s in the 6
      regions that reversed and 7.31 x 10(-3) mm2/s in the 6 regions that persisted (P
      < .036). With thrombolytic treatment, large ischemic lesions on DWI may reverse,
      and these areas display higher mean ADCs.

PMID- 11462302
TI  - Unilateral temporal lobe stroke causing ischemic transient global amnesia: role
      for diffusion-weighted imaging in the initial evaluation.
AB  - Ischemia has been proposed as a cause of transient global amnesia (TGA), but
      proof has been lacking. The authors performed magnetic resonance imaging on a 77
      year-old woman with classic TGA at 4 hours and at 6 days after the onset of
      symptoms. Her initial diffusion-weighted imaging (DWI) and apparent diffusion
      coefficient imaging suggested an acute infarct in the left mesial temporal lobe.
      Follow-up T2-weighted imaging at 6 days confirmed the lesion as an ischemic
      infarct, despite resolution of her symptoms. DWI permits early detection of small
      ischemic lesions and may identify patients with ischemic TGA who should be
      evaluated for potential sources of emboli.

PMID- 11462303
TI  - Dural arteriovenous fistula associated with prothrombin gene mutation.
AB  - An association between dural arteriovenous fistula and cerebral sinus thrombosis
      is reported. It is clear in several cases that thrombosis precedes the
      development of the fistula while it is unclear that it occurs in every case. The
      authors report a case of a woman with sinus thrombosis and presence of
      prothrombin gene mutation who subsequently developed a large dural arteriovenous
      fistula. Various possible factors involved in the pathogenesis of a dural fistula
      are discussed, with emphasis on underlying thrombophilia and oral contraceptive
      use in this patient.

PMID- 11462304
TI  - High-resolution magnetic resonance imaging reveals symmetric bitemporal cortical
      necrosis after carbon monoxide intoxication.
AB  - High-resolution magnetic resonance images obtained in a patient several months
      after carbon monoxide (CO) intoxication revealed nearly symmetric regional
      atrophy of both lateral temporal lobes. This pattern of cortical lesions after CO
      exposure has not been reported before. The patient suffered from severe cognitive
      deficits including a transient Kluver-Bucy-like behavior. This report underlines
      the value of high-resolution magnetic resonance imaging in chronic stages of CO
      intoxication in the attempt to understand the neuroanatomical bases of the
      observed behavior.

PMID- 11462305
TI  - Discordance between cerebral oxygen and glucose metabolism, and hemodynamics in a
      mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode patient.
AB  - A patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike
      episode (MELAS) syndrome underwent serial measurement of cerebral blood flow with
      xenon computed tomography (Xe-CBF) while presenting with strokelike episodes
      accompanied by a cerebral lesion. He underwent positron emission tomography (PET)
      measurement of the regional cerebral blood flow (PET-CBF), metabolic rate of
      oxygen (CMRO2), and glucose (CMRGlu) after his symptoms and lesion disappeared.
      During the symptomatic period, Xe-CBF and the Xe-CBF response to acetazolamide
      loading were well preserved both in and outside the low-density lesion. In the
      PET study, decreased CMRO2 and increased PET-CBF and CMRGlu were noted in the
      entire brain. The strokelike episodes of patients with MELAS are more likely
      attributed to the failure of oxygen metabolism than to a vascular accident.

PMID- 11462306
TI  - Intraosseous sacral myxopapillary ependymoma and the differential diagnosis of
      sacral tumors.
AB  - Although involvement of other regions of the spinal cord and brain stem is seen,
      myxopapillary ependymoma is most commonly found at the filum terminale or cauda
      equina. Less commonly, myxopapillary ependymoma may occur outside the central
      nervous system from direct metastatic extension of an intrathecal tumor, and
      rarely it may present as a primary tumor outside the thecal sac. The authors
      present a case of primary sacral myxopapillary ependymoma, which was first
      diagnosed as a chordoma. They then discuss the magnetic resonance imaging
      findings of this and other sacral tumors. Myxopapillary ependymoma should be
      considered in the differential diagnosis for a primary expansile sacral mass
      along with other lesions such as chordoma, aneurysmal bone cyst, and giant cell
      tumor.

PMID- 11462307
TI  - Cerebral vasculitis: diagnosis and follow-up with transcranial Doppler
      ultrasonography.
AB  - The authors report a patient with postpartum intracerebral hemorrhage associated
      with cerebral vasculitis. Cerebral circulation was assessed with transcranial
      Doppler (TCD) ultrasonography, magnetic resonance angiography, and conventional
      cerebral angiography. Initial TCD studies demonstrated bilateral patchy increased
      cerebral blood flow velocity (CBFV) in the anterior circulation with complete
      normalization during remission. This case report provides evidence that cerebral
      vasculitis leads to relevant CBFV changes and that the TCD technique may assist
      in diagnosis and follow-up of these patients.

PMID- 11462308
TI  - Clinical and magnetic resonance imaging regression of progressive multifocal
      leukoencephalopathy in an AIDS patient after intensive antiretroviral therapy.
AB  - A 36-year-old homosexual man with 6 months of visual symptoms and headaches had
      right homonymous hemianopia, mild new learning impairment, and alexia with
      agraphia. The initial brain magnetic resonance imaging (MRI) scan was reported
      consistent with left occipital infarction. Subsequent MRI demonstrated abnormal
      demyelination in subcortical white matter and deep parieto-occipital white matter
      bilaterally, but primarily left. Human immunodeficiency virus testing and
      cerebrospinal fluid polymerase chain reaction for JC virus DNA were both
      positive, consistent with progressive multifocal leukoencephalopathy (PML) with
      AIDS. His clinical status steadily deteriorated, and MRI white matter
      abnormalities worsened despite high-dose antiretroviral therapy. After the
      antiretroviral regimen was intensified by the addition of a protease inhibitor,
      rapid clinical and radiographic improvement occurred with subsequent MRI studies
      revealing only residual left parieto-occipital encephalomalacia. PML in AIDS
      patients has been associated with a nearly uniformly poor prognosis until recent
      reports of improved outcomes after highly active antiretroviral therapy. This
      patient with PML and AIDS similarly showed a robust clinical and MRI response to
      intensive antiretroviral combination therapy, which has been maintained for more
      than 3 years.

PMID- 11462309
TI  - Intracranial vasculitis and multiple abscesses in a pregnant woman.
AB  - Cerebral vasculitis is an unusual disorder with many causes. Infectious causes of
      cerebral vasculitis are predominantly bacterial or viral in nature. Purulent
      bacterial vasculitis is most often a complication of severe bacterial meningitis.
      The patient is a 25-year-old African American female, 25 weeks pregnant, who
      presented to the neurology service after a consult and referral from an outside
      hospital. She had a 1-month history of right sixth nerve palsy. Initial workup
      included a negative lumber puncture and a noninfused magnetic resonance imaging
      (MRI). Three days later, the patient developed right-sided migraine headaches and
      right third nerve palsy. The angiogram revealed diffuse irregularity and
      narrowing of the petrous, cavernous, and supraclinoid portions of the internal
      carotid and right middle cerebral arteries. Shortly thereafter, an MRI
      examination revealed diffuse leptomeningeal enhancement and abscess and a right
      parietal subdural empyema. Infectious vasculitis secondary to purulent meningitis
      has a rapidly progressive course and presents with cranial nerve palsy with
      involvement of the cavernous sinus. Although the association of this disease with
      pregnancy has not been established, it should be recognized that the early
      imaging studies may be negative or discordant and follow-up imaging might be
      necessary.

PMID- 11462310
TI  - Chronic pain: a challenge for primary care.

PMID- 11462311
TI  - Insulin therapy in poorly controlled type 2 diabetic patients: does it affect
      quality of life?
AB  - BACKGROUND: Strict glycaemic control in type 2 diabetic patients is recommended
      in a number of treatment protocols. However, although better glycaemic control
      prevents or postpones chronic diabetic complications, it remains uncertain how
      this affects quality of life in the short and long term. AIM: To study the impact
      of insulin therapy on glycaemic control and quality of life in type 2 diabetic
      patients, with secondary failure on maximal oral medication. DESIGN OF STUDY: Two
      separate sets of analyses were performed: a longitudinal analysis of those
      patients converted to insulin therapy and a comparison of 12-week outcomes
      between the two randomisation groups. SETTING: Ten general practices,
      participating in the Nijmegen Monitoring Project. METHOD: Patients, poorly
      controlled on maximal oral therapy, were stratified with respect to age and sex,
      and randomly allocated to insulin therapy in two different schedules: (a) after a
      12-week period with enhanced compliance to diet and oral therapy: or (b) as soon
      as secondary failure was established. Patients were referred to a diabetologist
      to start insulin therapy and were referred back to their general practitioner
      (GP) as soon as glycaemic control was stable. We assessed fasting blood glucose,
      HbA1c functional health, and quality of life (Sickness Impact Profile, COOP/WONCA
      charts, Diabetes Symptom Checklist) at baseline, after the patient was referred
      back to the GP, and nine months later. RESULTS: Of the 38 included patients,
      three patients dropped out and seven patients were not switched over to insulin
      therapy. In patients starting insulin therapy, mean HbA1c and fasting blood
      glucose level decreased from 9.5% to 7.6%, and from 12.0 mmol to 8.4 mmol,
      respectively (P < 0.001). The better control was accompanied by a decrease in
      hyperglycaemic complaints (P = 0.01). No increase in hypoglycaemic complaints was
      found. There were no statistically significant changes in quality-of-life
      parameters. After 12 weeks, patients directly referred to insulin therapy showed
      a statistically significant improvement in HbA1c and fasting glucose level, in
      contrast to patients with enhanced compliance. Quality-of-life scores did not
      significantly differ statistically. CONCLUSION: Insulin therapy in poorly
      controlled type 2 diabetic patients from general practice resulted in a
      significant clinical improvement of glycaemic control, accompanied by a reduction
      of hyperglycaemic complaints, without an increase in hypoglycaemic complaints or
      an adverse influence on quality of life.

PMID- 11462312
TI  - Otitis externa in UK general practice: a survey using the UK General Practice
      Research Database.
AB  - BACKGROUND: Otitis externa is a common clinical problem in general practice and
      yet there are remarkably few data available on the demographic characteristics of
      patients with this condition and the approaches used by general practitioners
      (GPs) in the United Kingdom (UK) to manage it. AIM: To define the descriptive
      epidemiology of otitis externa in the general population, to describe the first
      line drug treatment used by UK GPs, and to determine factors related to second
      disease episodes. DESIGN OF STUDY: Epidemiological data survey. SETTING: All
      cases of otitis externa occurring in 1997 in practices contributing data to the
      UK General Practice Research Database. METHOD: Data were extracted on age, sex,
      date of episode of otitis externa, treatment prescribed, co-existing diagnoses of
      eczema and diabetes, referral to ear, nose, and throat departments and occurrence
      of subsequent episodes of disease. Arbitrarily a second episode of disease was
      defined as persistence if it occurred at 28 days or fewer after the first episode
      and recurrence if it occurred at more than 28 days after the first episode.
      RESULTS: A diagnosis of otitis externa was common in all age groups and, except
      in the elderly, was more common in females than males. There was an increase in
      disease episodes at the end of the summer in all age groups except the 60 years
      and over group. In the majority of cases GPs prescribed ear drops (85%), but a
      significant proportion of patients were also prescribed oral antibiotics (21%).
      Referral to secondary care was uncommon (3%). Among patients prescribed ear-drop
      formulations, those containing both steroid and antibiotic or steroid alone were
      used most commonly and were associated with the lower rates of disease
      persistence but not recurrence. Among patients prescribed antibiotics,
      penicillins were prescribed most commonly. Disease persistence rates, and to a
      lesser extent disease recurrence rates, were higher in patients prescribed oral
      antibiotics. CONCLUSION: Otitis externa is a common condition and GPs can expect
      to see an excess of cases at the end of the summer. Topical ear drops are the
      most common treatment used in the UK. Patients prescribed steroid or
      steroid/antibiotic combination ear drops have fewer subsequent consultations for
      otitis externa over the following 28 days.

PMID- 11462313
TI  - The community prevalence of chronic pelvic pain in women and associated illness
      behaviour.
AB  - BACKGROUND: Chronic pelvic pain has often been described as a major women's
      health issue, but no information exists on the extent of the problem in the
      United Kingdom. AIM: To investigate the community prevalence of chronic pelvic
      pain and its effect on the lives of consulting and non-consulting women. DESIGN
      OF STUDY: Postal questionnaire survey. SETTING: Women aged 18 to 49 (n = 3916)
      randomly selected from the Oxfordshire Health Authority Register. METHOD: The
      questionnaire response rate (adjusted for non-deliveries) was 74% (2304/3106).
      Chronic pelvic pain was defined as recurrent or constant pelvic pain of at least
      six months' duration, unrelated to periods, intercourse, or pregnancy. Case
      subgroups comprised recent consulters, past consulters, and non-consulters. Women
      who reported dysmenorrhoea alone formed a comparison group. RESULTS: The three
      month prevalence of chronic pelvic pain was 24.0% (95% CI = 22.1% to 25.8%). One
      third of women reported pain that started more than five years ago. Recent
      consulters (32% of cases) were most affected by their symptoms in terms of pain
      severity, use of health care, physical and mental health scores, sleep quality,
      and pain-related absence from work. Non-consulters (41% of cases) did not differ
      from women with dysmenorrhoea in terms of symptom-related impairment.
      Irrespective of consulting behaviour, a high rate of symptom-related anxiety was
      found in women with chronic pelvic pain (31%) compared with women with
      dysmenorrhoea (7%). CONCLUSIONS: This study showed a high community prevalence of
      chronic pelvic pain in women of reproductive age. Cases varied substantially in
      the degree to which they were affected by their symptoms. The high symptom
      related anxiety in these women emphasises the need for more information about
      chronic pelvic pain and its possible causes.

PMID- 11462314
TI  - Urinary incontinence in older people in the community: a neglected problem?
AB  - BACKGROUND: The prevalence and impact of urinary incontinence has been
      investigated much less in older men than in older women. It is suggested that
      those who perceive that their daily lives are affected should have priority for
      services. However, many people do not seek medical help, even though they may be
      severely affected. AIM: To investigate unmet need in relation to the prevalence
      and impact on everyday life of urinary incontinence in men and women over the age
      of 65 years. DESIGN OF STUDY: Cross-sectional survey to measure prevalence of
      urinary incontinence, the impact on people's lives, use of protection, and health
      services. SETTING: Stratified random sample of 2000 community-living elderly
      (equal numbers of men and women, aged 65 to 74 years and over 75 years) in 11
      general practices in a British city. RESULTS: The response rate was 79%. The
      overall prevalence of incontinence in the previous month was 31% for women and
      23% for men. Women generally had more severe frequency of incontinence and a
      greater degree of wetness than men. Protection use was greater in women than in
      men. Only 40% of men and 45% of women with incontinence had accessed health
      services. Significant predictors of the use of health services were: incontinence
      reported as a problem, increased frequency of incontinence, and greater degree of
      wetness. About one-third of people who leaked with severe frequency or who
      reported that it was a problem had not accessed NHS services for incontinence.
      CONCLUSIONS: Urinary incontinence is a common problem for older men and women
      living in the community and can have a deleterious effect on their lives. There
      is the opportunity to improve the lives of many older people with urinary
      incontinence, probably by a combination of increased public, patient, and
      professional awareness that should lead to earlier presentation and initiation of
      effective care.

PMID- 11462315
TI  - Frequency of attendance in general practice and symptoms before development of
      chronic fatigue syndrome: a case-control study.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) research has concentrated on
      infective, immunological, and psychological causes. Illness behaviour has
      received less attention, with most research studying CFS patients after
      diagnosis. Our previous study on the records of an insurance company showed a
      highly significant increase in illness reporting before development of CFS. AIM:
      To investigate the number and type of general practitioner (GP) consultations by
      patients with CFS for 15 years before they develop their condition. DESIGN OF
      STUDY: Case-control study in 11 general practices in Devon. SETTING: Forty-nine
      patients with CFS (satisfying the Centers for Disease Control criteria), 49 age,
      sex, and general practice matched controls, and 37 patients with multiple
      sclerosis (MS) were identified from the general practices' computerised
      databases. METHOD: The number of general practice consultations and symptoms
      recorded in three five-year periods (quinquennia) were counted before development
      of the patients' condition. RESULTS: The median number of consultations was
      significantly higher for CFS patients than that of matched controls in each of
      the quinquennia: ratios for first quinquennium = 1.88, P = 0.01; second
      quinquennium = 1.70, P = 0.005; last quinquennium = 2.25, P < 0.001. More CFS
      patients than controls attended for 13 of the 18 symptoms studied. Significant
      increases were found for upper respiratory tract infection (P < 0.001), lethargy
      (P < 0.001), and vertigo (P = 0.02). Similar results were found for CFS patients
      when compared with MS. CONCLUSIONS: CFS patients consulted their GP more
      frequently in the 15 years before development of their condition, for a wide
      variety of complaints. Several possibilities may explain these findings. The
      results support the hypothesis that behavioural factors have a role in the
      aetiology of CFS.

PMID- 11462316
TI  - Learning preferences and learning styles: a study of Wessex general practice
      registrars.
AB  - BACKGROUND: Experienced trainers know that individual registrars react very
      differently to identical learning experiences generated during the year in
      practice. This divergence reflects differences in registrars' learning styles.
      Only one study of United Kingdom (UK) general practitioners' learning styles has
      been undertaken. Learning style theory predicts that matching learning preference
      with learning style will enhance learning. This paper researches for the first
      time the evidence in the setting of UK general practice. AIM: To determine, for
      the general practice registrars within the Wessex Region, the nature of their
      learning preferences and learning styles and correlations between them. DESIGN OF
      STUDY: A descriptive confidential postal questionnaire survey. SETTING: Fifty
      seven registrars identified in the Wessex Region with a minimum experience of six
      months in general practice. METHOD: The questionnaire gathered demographic data
      (sex, age, experience in general practice, years post-registration, and
      postgraduate qualifications). Learning preferences were elicited using a six
      point Likert scale for learning experiences. The Honey and Mumford Learning Style
      Questionnaire (LSQ) elicited the registrars' learning styles. A second
      questionnaire was sent to non-responders. RESULTS: The response rate was 74%.
      Registrars report that interactive learning with feedback is preferred, but more
      passive learning formats remain valued. A wide range of learning style scores was
      found. The Honey and Mumford LSQ mean scores fell within the reflector-theorist
      quadrant. Evidence for correlations between learning preferences and learning
      styles was also found, in particular for the multiple choice question and audit
      components of summative assessment. CONCLUSION: A wide range of registrar
      learning styles exists in Wessex, and initial correlations are described between
      learning preferences and learning styles as predicted by style theory. This work
      sets the stage for a shared understanding and use of learning style theory to
      enhance professional learning throughout a GP's career. More research is needed
      in this domain.

PMID- 11462317
TI  - Chlamydia trachomatis: opportunistic screening in primary care.
AB  - Following the publication of the Chief Medical Officer's report on chlamydial
      screening, we identified the sexual health of young women as an area for concern.
      As part of our review we decided to opportunistically search for chlamydial
      genital infections using a non-invasive technique. Sexually active women under 25
      years of age were invited to submit a first void urine sample for polymerase
      chain reaction analysis. Over the period of a year we found out that 10.9% of
      sexually active young women tested positive for chlamydia in our practice.

PMID- 11462318
TI  - Frequent attenders in general practice: a retrospective 20-year follow-up study.
AB  - We describe a 20-year retrospective study of 58 patients with a cross-matched
      control group in one practice, who initially attended more than 12 times in 1975.
      The study establishes that frequent attendance is not consistent; the majority of
      high-attending patients in general practice revert over a short period of time to
      a normal consulting pattern. Diseases, rather than patients, appear to dictate
      high consulting rates. Consistent high attendance is largely owing to multiple
      pathology.

PMID- 11462319
TI  - Pitfalls of 'inert' ingredients.

PMID- 11462320
TI  - Meeting the National Service Framework for coronary heart disease: which patients
      have untreated high blood pressure?
AB  - BACKGROUND: The National Service Framework for coronary heart disease requires
      primary care teams to identify patients who are at high risk of cardiovascular
      events and treat those with high blood pressure. However, there are no data on
      how many must be assessed, how much cardiovascular disease can be prevented or
      which patients are most likely to benefit. AIM: To estimate the potential number
      of patients who are eligible for blood pressure assessment, the number of
      preventable cardiovascular disease events and the relative efficiency of the
      strategy in different age groups. DESIGN OF STUDY: Modelling exercise. SETTING:
      Hypothetical population of 100,000. METHOD: The age-sex specific prevalence of
      cardiovascular risk factors and of current anti-hypertensive treatment were
      obtained from published sources and combined with published estimates of the
      effectiveness of anti-hypertensive treatment. From these data were calculated
      numbers of persons eligible for assessment and treatment, and numbers of
      preventable cardiovascular events. RESULTS: There were 79,607 persons eligible
      for assessment and 5888 eligible for treatment. Treatment could prevent between
      101 and 139 cardiovascular events annually. There were 11,571 persons aged over
      65 years and eligible for assessment and 4655 eligible for treatment. Treatment
      could prevent 85 to 117 cardiovascular events annually. No cardiovascular events
      are prevented in persons aged under 45 years. CONCLUSION: Confining assessment to
      the 16% who are aged over 65 years prevents 85% of the population's avoidable
      cardiovascular disease. Primary care teams should assess and treat persons aged
      over 65 years before assessing younger patients. No health benefit results from
      assessing persons aged under 45 years.

PMID- 11462321
TI  - James Mackenzie Lecture. Trust--in general practice.

PMID- 11462322
TI  - General practitioner's awareness of colorectal cancer: has referral improved?

PMID- 11462323
TI  - NHS direct.

PMID- 11462324
TI  - Specialist outreach in the NHS.

PMID- 11462325
TI  - Personality-targeted strategies for explaining immunisation risk.

PMID- 11462326
TI  - Electrodiagnosis in carpal tunnel syndrome.

PMID- 11462327
TI  - Adverse drug reactions.

PMID- 11462328
TI  - Diabetes in primary care: study raises questions.

PMID- 11462329
TI  - Medical school selection procedures.

PMID- 11462330
TI  - Deprivation payments.

PMID- 11462331
TI  - Sexually transmitted infections in primary care: a need for education.

PMID- 11462332
TI  - GPs prescribing specialist medicines.

PMID- 11462333
TI  - A simple, practical method for optimizing aesthetic results of CEREC milled
      restorations.

PMID- 11462334
TI  - Multimedia patient education: patients taking ownership of their needs.

PMID- 11462335
TI  - Computerization can make you a better dentist.

PMID- 11462336
TI  - Transform your practice with high technique, Part 2: How technology solves
      staffing problems.

PMID- 11462337
TI  - Researcher finds link among stress, pain, and immune function. Root canal
      procedure used as model to determine link.

PMID- 11462338
TI  - Black tea; white teeth. Research suggests beverage may be powerful cavity
      fighting tool.

PMID- 11462339
TI  - Ergonomics: doing the right thing!

PMID- 11462340
TI  - Advantages of expanding the role of the registered dental hygienist in tooth
      whitening.

PMID- 11462341
TI  - The particulars of procedures.

PMID- 11462342
TI  - Managing patients with diabetes, Part 2.

PMID- 11462343
TI  - Diagnosis and treatment of dental caries: a microdentistry approach.

PMID- 11462344
TI  - Impression terminology.

PMID- 11462345
TI  - The choice is ours.

PMID- 11462346
TI  - A current protocol for nonsurgical periodontal therapy.

PMID- 11462347
TI  - Mini dental implants: enhancing patient satisfaction and practice income.

PMID- 11462348
TI  - Aesthetic rehabilitation of the patient with temporomandibular dysfunction: a 6
      year postoperative case study.

PMID- 11462349
TI  - Diagnosing salivary gland disease.

PMID- 11462350
TI  - Use of the POLY and AART occlusal techniques in the fabrication of a fixed
      detachable implant reconstruction.

PMID- 11462351
TI  - [Acidemia, propionic].

PMID- 11462352
TI  - [Aciduria, argininosuccinic].

PMID- 11462353
TI  - [Aciduria, glutaric (type 1)].

PMID- 11462355
TI  - [Acoustic neuromata].

PMID- 11462354
TI  - [Aciduria, glutaric (type 2)].

PMID- 11462356
TI  - [Acrocallosal syndrome (Schinzel type)].

PMID- 11462357
TI  - [Acrocephalopolydactylous dysplasia (Elejalde syndrome)].

PMID- 11462358
TI  - [Acrocephalopolysyndactyly].

PMID- 11462359
TI  - [Acrocephalosyndactyly type I].

PMID- 11462360
TI  - [Abnormal morphogenesis].

PMID- 11462361
TI  - [Acrocephalosyndactyly type III].

PMID- 11462362
TI  - [Acrocephalosyndactyly type V].

PMID- 11462363
TI  - [Acrodysostosis].

PMID- 11462364
TI  - [Acrofacial dysostosis].

PMID- 11462365
TI  - [Acrofacial dysostosis, Nager type].

PMID- 11462366
TI  - [Acrofacial dysostosis, postaxial type (postaxial acrofacial dysostosis: POAD)].

PMID- 11462367
TI  - [Acromegaloid facial appearance syndrome].

PMID- 11462368
TI  - [Acromegaloid phenotype-cutis verticis gyrata-corneal leukoma].

PMID- 11462369
TI  - [Acromelic frontonasal dysostosis].

PMID- 11462370
TI  - [Acromesomelic dysplasia].

PMID- 11462371
TI  - [Acromicric dysplasia].

PMID- 11462372
TI  - [Acro-renal-mandibular syndrome].

PMID- 11462373
TI  - [Acyl-CoA dehydrogenase deficiency (very-long-chain, long-chain, medium-chain,
      short-chain), mitochondrial].

PMID- 11462374
TI  - [Adenine phosphoribosyltransferase deficiency].

PMID- 11462375
TI  - [Adenosine deaminase deficiency].

PMID- 11462376
TI  - [Adrenoleukodystrophy].

PMID- 11462377
TI  - [Agnathia-holoprosencephaly].

PMID- 11462378
TI  - [Agnathia-microstomia-synotia].

PMID- 11462380
TI  - [Albinism].

PMID- 11462379
TI  - [Aicardi syndrome].

PMID- 11462381
TI  - [Albinism, Waardenburg type--Hirschsprung aganglionosis].

PMID- 11462382
TI  - [Alexander disease].

PMID- 11462383
TI  - [Alopecia-anosmia-deafness-hypogonadism syndrome (Johnson type)].

PMID- 11462384
TI  - [Alpers disease].

PMID- 11462385
TI  - [Alzheimer disease, familial].

PMID- 11462386
TI  - [Amelo-cerebro-hypohidrotic syndrome].

PMID- 11462387
TI  - [Amelo-onycho-hypohidrotic syndrome].

PMID- 11462388
TI  - [Amniotic bands syndrome].

PMID- 11462389
TI  - [Amyloidoses].

PMID- 11462390
TI  - [Amyotrophic lateral sclerosis].

PMID- 11462391
TI  - [Androgen resistance syndrome].

PMID- 11462392
TI  - [Anemia, hereditary sideroblastic].

PMID- 11462393
TI  - [Diamond-Blackfan syndrome].

PMID- 11462394
TI  - [Anemia, hypoplastic-triphalangeal thumbs (Aase-Smith type)].

PMID- 11462395
TI  - [Anencephaly].

PMID- 11462396
TI  - [Angelman syndrome].

PMID- 11462397
TI  - [Klippel-Trenaunay-Weber syndrome].

PMID- 11462398
TI  - [Aniridia].

PMID- 11462399
TI  - [Anophthalmia-limb anomalies].

PMID- 11462400
TI  - [Anorchia].

PMID- 11462401
TI  - [Anorectal malformation].

PMID- 11462402
TI  - [Anosmia, congenital].

PMID- 11462403
TI  - [Antley-Bixler syndrome].

PMID- 11462404
TI  - [Etiology and initiating mechanisms of abnormal morphogenesis].

PMID- 11462405
TI  - [Anus-hand-ear syndrome (Townes-Brocks syndrome)].

PMID- 11462406
TI  - [Aorta].

PMID- 11462407
TI  - [Arachnodactyly, contractural Beals type].

PMID- 11462408
TI  - [AREDYLD syndrome].

PMID- 11462409
TI  - [Argininemia].

PMID- 11462410
TI  - [Arrhythmia, with long QT interval without deafness].

PMID- 11462411
TI  - [Arrhythmia, Wolff-Parkinson-White type].

PMID- 11462412
TI  - [Arterio-hepatic dysplasia].

PMID- 11462413
TI  - [Arthrogryposis].

PMID- 11462414
TI  - [Arthro-ophthalmopathy, hereditary, progressive, Stickler type & Weissenbacher
      Zweymuller variant].

PMID- 11462415
TI  - [Asphyxiating thoracic dysplasia].

PMID- 11462416
TI  - [Asplenia syndrome].

PMID- 11462417
TI  - [Ataxia, Friedreich type].

PMID- 11462418
TI  - [Ataxia-hypogonadism syndrome (Boucher-Neuhauser syndrome)].

PMID- 11462419
TI  - [Ataxia-telangiectasia].

PMID- 11462420
TI  - [ATR-16].

PMID- 11462421
TI  - [Atrial septal defects (ASD)].

PMID- 11462422
TI  - [Axial mesodermal dysplasia].

PMID- 11462423
TI  - [Bannayan-Zonana syndrome].

PMID- 11462424
TI  - [Barber-Say syndrome].

PMID- 11462425
TI  - [Bardet-Biedl syndrome].

PMID- 11462426
TI  - [Barraquer-Simons syndrome].

PMID- 11462427
TI  - [Barth syndrome].

PMID- 11462428
TI  - [Bartter syndrome].

PMID- 11462429
TI  - [Beare-Stevenson cutis gyrata syndrome].

PMID- 11462430
TI  - [Becker nevus syndrome].

PMID- 11462431
TI  - [Beckwith-Wiedemann syndrome].

PMID- 11462432
TI  - [Bilginturan syndrome].

PMID- 11462433
TI  - [Biopterin synthesis deficiency (involv. DHPR deficiency)].

PMID- 11462434
TI  - [Biotinidase deficiency].

PMID- 11462435
TI  - [Bladder extrophy].

PMID- 11462436
TI  - [Blau syndrome].

PMID- 11462437
TI  - [Blepharo-cheilo-dontic (BCD) syndrome].

PMID- 11462438
TI  - [Blepharofacioskeletal syndrome].

PMID- 11462439
TI  - [Blepharophimosis, epicanthus inversus and ptosis syndrome (BPES)].

PMID- 11462440
TI  - [Bloom syndrome].

PMID- 11462441
TI  - [Borjeson-Forssman-Lehmann syndrome].

PMID- 11462442
TI  - [Brachydactyly, hereditary solitary].

PMID- 11462443
TI  - [Brain, arachnoid cysts, temporal lobe agenesis].

PMID- 11462444
TI  - [Branchio-oculo-facial (BOF) syndrome].

PMID- 11462445
TI  - [Branchio-oto-renal (BOR) syndrome].

PMID- 11462446
TI  - [Branchio-skeleto-genital syndrome].

PMID- 11462447
TI  - [Brachmann-de Lange syndrome].

PMID- 11462448
TI  - [Dysmorphology approach].

PMID- 11462449
TI  - [Breast].

PMID- 11462451
TI  - [C syndrome].

PMID- 11462450
TI  - [Burton skeletal dysplasia].

PMID- 11462452
TI  - [Campomelic or camptomelic dysplasia (CMPD)].

PMID- 11462453
TI  - [Camptodactyly, hereditary solitary].

PMID- 11462454
TI  - [Trismus-pseudocamptodactyly syndrome].

PMID- 11462455
TI  - [Cancer, breast, familial].

PMID- 11462456
TI  - [Cancer, colorectal].

PMID- 11462457
TI  - [Carnitine palmitoyltransferase deficiency (I, II)].

PMID- 11462458
TI  - [Carbamoyl phosphate synthetase I deficiency].

PMID- 11462459
TI  - [Cardiofacial syndrome, asymmetric or asymmetrical crying facies (ACF)].

PMID- 11462460
TI  - [Cardio-facio-cutaneous (CFC) syndrome].

PMID- 11462461
TI  - [Cardiomyopathy, familial dilated].

PMID- 11462462
TI  - [Carey-Fineman-Ziter (CFZ) syndrome].

PMID- 11462463
TI  - [Carnitine transport defect].

PMID- 11462464
TI  - [Cat eye syndrome].

PMID- 11462465
TI  - [Molecular cytogenetic diagnosis of congenital malformation syndromes].

PMID- 11462466
TI  - [Cataract].

PMID- 11462467
TI  - [Cataracts-oto-dental defects (Nance-Horan syndrome)].

PMID- 11462468
TI  - [Caudal regression syndrome].

PMID- 11462469
TI  - [Cerebellar agenesis].

PMID- 11462470
TI  - [Cerebello-trigeminal dermal dysplasia].

PMID- 11462472
TI  - [Cerebro-costo-mandibular syndrome].

PMID- 11462471
TI  - [Cerebral gigantism].

PMID- 11462473
TI  - [Cerebro-nephro-osteodysplasia (Hutterite type)].

PMID- 11462474
TI  - [Cerebro-oculo-facio-skeletal (COFS) syndrome].

PMID- 11462475
TI  - [Cerebro-reno-digital syndromes].

PMID- 11462476
TI  - [Wildervanck (cervico-oculo-acoustic) syndrome].

PMID- 11462477
TI  - [CHARGE association].

PMID- 11462478
TI  - [Chediak-Higashi syndrome].

PMID- 11462480
TI  - [Chondrodysplasia punctata].

PMID- 11462479
TI  - [Cherubism].

PMID- 11462481
TI  - [Chondrodystrophic myotonia, Schwartz-Jampel type].

PMID- 11462482
TI  - [Chondroectodermal dysplasia].

PMID- 11462483
TI  - [Chromosome 1].

PMID- 11462484
TI  - [Chromosome 2].

PMID- 11462485
TI  - [Chromosome 3].

PMID- 11462486
TI  - [Chromosome 4].

PMID- 11462487
TI  - [Chromosome 5].

PMID- 11462488
TI  - [Chromosome 6].

PMID- 11462489
TI  - [Chromosome 7].

PMID- 11462490
TI  - [Chromosome 8].

PMID- 11462491
TI  - [Chromosome 9].

PMID- 11462492
TI  - [Chromosome 10].

PMID- 11462493
TI  - [Textbooks and databases useful to refer for diagnosis of congenital anomalies].

PMID- 11462494
TI  - [Chromosome 11].

PMID- 11462495
TI  - [Chromosome 12].

PMID- 11462496
TI  - [Chromosome 13].

PMID- 11462497
TI  - [Chromosome 14].

PMID- 11462498
TI  - [Chromosome 15].

PMID- 11462499
TI  - [Chromosome 16].

PMID- 11462500
TI  - [Chromosome 17].

PMID- 11462501
TI  - [Chromosome 18].

PMID- 11462502
TI  - [Chromosome 19].

PMID- 11462503
TI  - [Chromosome 20].

PMID- 11462504
TI  - [Chromosome 21].

PMID- 11462505
TI  - [Chromosome 22].

PMID- 11462506
TI  - [Chromosome instability, Nijmegen type].

PMID- 11462507
TI  - [Chromosome mosaicism, 45,X/46,XY type].

PMID- 11462508
TI  - [Chromosome tetraploidy].

PMID- 11462509
TI  - [Chromosome triploidy].

PMID- 11462510
TI  - [Chromosome X, poly-X].

PMID- 11462511
TI  - [Chromosome XYY, XXY].

PMID- 11462512
TI  - [Citrullinemia].

PMID- 11462513
TI  - [Cleft lip].

PMID- 11462514
TI  - [Cleft palate].

PMID- 11462515
TI  - [Pierre Robin syndrome (Robin sequence)].

PMID- 11462516
TI  - [Social acceptance of disabled persons].

PMID- 11462517
TI  - [Cleidocranial dysplasia].

PMID- 11462518
TI  - [Cockayne syndrome].

PMID- 11462519
TI  - [CODAS syndrome].

PMID- 11462520
TI  - [Coffin-Lowry syndrome].

PMID- 11462521
TI  - [Coffin-Siris syndrome].

PMID- 11462522
TI  - [Cohen syndrome].

PMID- 11462523
TI  - [Colon, aganglionosis].

PMID- 11462524
TI  - [Colon, atresia or stenosis].

PMID- 11462525
TI  - [Colon, duplication].

PMID- 11462526
TI  - [Color blindness, blue monocone-monochromatic].

PMID- 11462527
TI  - [Colpocephaly].

PMID- 11462528
TI  - [Congenital hypothalamic hamartoma syndrome].

PMID- 11462529
TI  - [Contractures, congenital lethal Finnish type].

PMID- 11462530
TI  - [Contractures-muscle atrophy-oculomotor apraxia].

PMID- 11462531
TI  - [Convulsion, benign familial neonatal].

PMID- 11462532
TI  - [Corneal dystrophy, endothelial].

PMID- 11462533
TI  - [Corpus callosum agenesis].

PMID- 11462534
TI  - [Cortical hyperostosis, infantile].

PMID- 11462535
TI  - [Costello syndrome].

PMID- 11462536
TI  - [Craniofacial dysostosis].

PMID- 11462537
TI  - [Morphogenesis in human embryos and fetuses].

PMID- 11462538
TI  - [Cranio-carpo-tarsal dysplasia, whistling face type].

PMID- 11462539
TI  - [Cranio-cerebello-cardiac (3C) syndrome].

PMID- 11462540
TI  - [Craniodiaphyseal dysplasia].

PMID- 11462541
TI  - [Craniodiaphyseal dysplasia, Lenz-Majewski type].

PMID- 11462542
TI  - [Cranio-ectodermal dysplasia].

PMID- 11462543
TI  - [Craniofacial-deafness-hand syndrome].

PMID- 11462544
TI  - [Craniofrontonasal dysplasia].

PMID- 11462545
TI  - [Craniometaphyseal dysplasia].

PMID- 11462547
TI  - [Crigler-Najjar syndrome].

PMID- 11462546
TI  - [Craniosynostosis].

PMID- 11462548
TI  - [Cutis laxa].

PMID- 11462549
TI  - [Cyclopia].

PMID- 11462550
TI  - [Cystic fibrosis].

PMID- 11462551
TI  - [Cystic hygroma].

PMID- 11462552
TI  - [Cystinuria].

PMID- 11462553
TI  - [Darier disease].

PMID- 11462554
TI  - [da-Silva syndrome].

PMID- 11462555
TI  - [Deafness].

PMID- 11462556
TI  - [Deafness-onycho-osteodystrophy-retardation-seizures (DOORS)].

PMID- 11462557
TI  - [Deafness-triphalangeal thumbs-onychodystrophy].

PMID- 11462558
TI  - [Birth defect syndrome and bioethics].

PMID- 11462559
TI  - [Dejerine-Sottas disease].

PMID- 11462560
TI  - [Dentatorubropallidoluysian degeneration, hereditary].

PMID- 11462561
TI  - [Dermal hypoplasia, focal].

PMID- 11462562
TI  - [Dermatoarthritis, familial histiocytic].

PMID- 11462563
TI  - [Desbuquois syndrome].

PMID- 11462564
TI  - [Dextrocardia-bronchiectasis-sinusitis syndrome].

PMID- 11462565
TI  - [Diabetes (insipidus/mellitus)-optic atrophy-deafness].

PMID- 11462566
TI  - [Diaphragmatic hernia].

PMID- 11462567
TI  - [Diaphyseal dysplasia].

PMID- 11462568
TI  - [Diastematomyelia].

PMID- 11462569
TI  - [Diastrophic dysplasia].

PMID- 11462570
TI  - [Digito-palatal syndrome (Stevenson type)].

PMID- 11462571
TI  - [Digito-reno-cerebral syndrome].

PMID- 11462572
TI  - [Dihydropyrimidine dehydrogenase deficiency].

PMID- 11462574
TI  - [Dubin-Johnson syndrome].

PMID- 11462573
TI  - [Dopamin beta-hydroxylase deficiency, congenital].

PMID- 11462575
TI  - [Dubowitz syndrome].

PMID- 11462576
TI  - [Dwarfism (short limbed)--Peters anomaly of the eye].

PMID- 11462577
TI  - [Dwarfism, dyssegmental, Rolland-Desbuquois type].

PMID- 11462578
TI  - [Dwarfism, dyssegmental, Silverman-Handmaker type].

PMID- 11462579
TI  - [Dwarfism, Laron type].

PMID- 11462580
TI  - [Dwarfism, osteodysplastic primordial, types I, II, III].

PMID- 11462581
TI  - [Dwarfism-dysmorphic facies-retardation, Pitt type, Pitt-Rogers-Danks syndrome,
      Wolf-Hirschhorn syndrome, 4p-syndrome].

PMID- 11462582
TI  - [Dyggve-Melchior-Clausen syndrome].

PMID- 11462583
TI  - [Dyschondrosteosis].

PMID- 11462584
TI  - [Dysosteosclerosis].

PMID- 11462585
TI  - [Earlobe, attached].

PMID- 11462586
TI  - [Ectodermal dysplasia, Basan type].

PMID- 11462587
TI  - [Ectodermal dysplasia, Christ-Siemens-Touraine type].

PMID- 11462588
TI  - [Ectodermal dysplasia, congenital facial, Setleis type].

PMID- 11462589
TI  - [Ectodermal dysplasia, Hay-Wells type].

PMID- 11462590
TI  - [Ectodermal dysplasia, hidrotic].

PMID- 11462591
TI  - [Ectodermal dysplasia, Passarge type].

PMID- 11462592
TI  - [Ectodermal dysplasia, Rapp-Hodgkin type].

PMID- 11462593
TI  - [Ectodermal dysplasia-ectrodactyly-macular dystrophy].

PMID- 11462594
TI  - [A view of the prevention for the birth defect syndrome].

PMID- 11462595
TI  - [Ectro-amelia syndrome].

PMID- 11462596
TI  - [Ectrodactyly, split hand/split foot malformation].

PMID- 11462597
TI  - [Ectrodactyly-ectodermal dysplasia-clefting syndrome].

PMID- 11462598
TI  - [Ehlers-Danlos syndrome].

PMID- 11462599
TI  - [Emery-Dreifuss syndrome].

PMID- 11462600
TI  - [Encephalocele].

PMID- 11462601
TI  - [Encephalocraniocutaneous lipomatosis].

PMID- 11462602
TI  - [Encephalopathy, necrotizing].

PMID- 11462603
TI  - [Enchondromatosis (Ollier disease)].

PMID- 11462604
TI  - [Enchondromatosis and hemangiomas (Maffucci syndrome)].

PMID- 11462605
TI  - [Endocrine neoplasia, multiple type 1].

PMID- 11462607
TI  - [Endosteal hyperostosis].

PMID- 11462606
TI  - [Endocrine neoplasia, multiple type 2].

PMID- 11462608
TI  - [Epidermolysis bullosum, type I, II, III].

PMID- 11462609
TI  - [Epiphyseal dysplasia, multiple].

PMID- 11462610
TI  - [Epiphyseal stippling syndrome].

PMID- 11462611
TI  - [Exostoses, multiple cartilaginous].

PMID- 11462612
TI  - [Exstrophy of cloaca sequence].

PMID- 11462613
TI  - [Eye, anterior segment dysgenesis].

PMID- 11462615
TI  - [Eye, hypertelorism].

PMID- 11462614
TI  - [Eye, Duane retraction syndrome].

PMID- 11462616
TI  - [Eye, keratoconus].

PMID- 11462617
TI  - [Eye, microphthalmia/coloboma].

PMID- 11462618
TI  - [F-syndrome].

PMID- 11462619
TI  - [Fabry disease].

PMID- 11462620
TI  - [Face, median cleft face syndrome].

PMID- 11462621
TI  - [Facial cleft, lateral, oblique].

PMID- 11462622
TI  - [Facial clefting syndrome, Gypsy type].

PMID- 11462623
TI  - [Fanconi-Bickel syndrome].

PMID- 11462624
TI  - [Risk evaluation for human teratogenic factors].

PMID- 11462625
TI  - [Femoral hypoplasia-unusual facies syndrome].

PMID- 11462626
TI  - [Fetal alcohol syndrome].

PMID- 11462627
TI  - [Fetal aminoglycoside ototoxicity].

PMID- 11462628
TI  - [Fetal aminopterin syndrome].

PMID- 11462629
TI  - [Fetal angiotensin converting enzyme (ACE) inhibition renal failure].

PMID- 11462630
TI  - [Fetal barbiturate effects].

PMID- 11462631
TI  - [Fetal cytomegalovirus syndrome].

PMID- 11462632
TI  - [Fetal effects from maternal diabetes].

PMID- 11462633
TI  - [Fetal hydantoin syndrome].

PMID- 11462634
TI  - [Fetal lithium effects].

PMID- 11462635
TI  - [Fetal methylmercury effects].

PMID- 11462636
TI  - [Fetal parvovirus infection].

PMID- 11462637
TI  - [Fetal radiation syndrome].

PMID- 11462639
TI  - [Fetal rubella syndrome].

PMID- 11462638
TI  - [Fetal retinoid syndrome].

PMID- 11462640
TI  - [Fetal syphilis syndrome].

PMID- 11462641
TI  - [Fetal thalidomide syndrome].

PMID- 11462642
TI  - [Fetal toxoplasmosis syndrome].

PMID- 11462643
TI  - [Fetal trimethadione syndrome].

PMID- 11462644
TI  - [Fetal valproate syndrome].

PMID- 11462645
TI  - [Fetal warfarin syndrome].

PMID- 11462646
TI  - [Fever, familial Mediterranean].

PMID- 11462647
TI  - [FG syndrome].

PMID- 11462648
TI  - [Fibrochondrogenesis].

PMID- 11462649
TI  - [Fibrodysplasia ossificans progressiva (FOP)].

PMID- 11462650
TI  - [McCune-Albright syndrome].

PMID- 11462651
TI  - [Floating-Harbor syndrome].

PMID- 11462652
TI  - [Forsius-Eriksson syndrome].

PMID- 11462653
TI  - [Frontonasal dysplasia].

PMID- 11462654
TI  - [Fraser syndrome].

PMID- 11462656
TI  - [Fructose-1,6-bisphosphatase deficiency].

PMID- 11462655
TI  - [Frontometaphyseal dysplasia].

PMID- 11462657
TI  - [Fryns syndrome].

PMID- 11462659
TI  - [Fucosidosis].

PMID- 11462658
TI  - [Prenatal genetic diagnosis and fetal therapy].

PMID- 11462660
TI  - [Active ring X chromosome].

PMID- 11462661
TI  - [G syndrome].

PMID- 11462662
TI  - [Galactosemia].

PMID- 11462663
TI  - [Gastroschisis].

PMID- 11462664
TI  - [Gaucher disease].

PMID- 11462665
TI  - [Geleophysic dwarfism].

PMID- 11462666
TI  - [Gerstmann-Straussler syndrome].

PMID- 11462668
TI  - [Gingival fibromatosis].

PMID- 11462667
TI  - [Gilbert syndrome].

PMID- 11462669
TI  - [Gingival multiple hamartoma syndrome].

PMID- 11462670
TI  - [Glycogen storage disease (I-VIII)].

PMID- 11462671
TI  - [GM1 gangliosidosis].

PMID- 11462672
TI  - [GM2 gangliosidosis].

PMID- 11462673
TI  - [Goldberg-Shprintzen syndrome].

PMID- 11462674
TI  - [Gonadal dysgenesis, XX type & XY type].

PMID- 11462675
TI  - [Gorlin-Chaudhry-Moss syndrome].

PMID- 11462676
TI  - [Gracile bone dysplasia].

PMID- 11462677
TI  - [Grebe syndrome].

PMID- 11462679
TI  - [Gyrate atrophy of the choroid and retina].

PMID- 11462678
TI  - [Growth retardation-alopecia-pseudoanodontia-optic atrophy].

PMID- 11462680
TI  - [Hair, uncombable-crystalline cataract].

PMID- 11462681
TI  - [Hair-nail ectodermal dysplasia].

PMID- 11462682
TI  - [Hajdu-Cheney syndrome].

PMID- 11462683
TI  - [Hallervorden-Spatz disease].

PMID- 11462684
TI  - [Hand, ulnar and fibular ray deficiency, Weyers type].

PMID- 11462685
TI  - [Hand-foot-genital syndrome].

PMID- 11462686
TI  - [Hardikar syndrome].

PMID- 11462687
TI  - [Hartnup disorder].

PMID- 11462688
TI  - [HDR syndrome].

PMID- 11462689
TI  - [Heart-hand syndrome].

PMID- 11462690
TI  - [Hemangioma-thrombocytopenia syndrome].

PMID- 11462691
TI  - [Heme oxygenase 1 deficiency].

PMID- 11462692
TI  - [Hemifacial atrophy, progressive].

PMID- 11462693
TI  - [Hemihypertrophy].

PMID- 11462694
TI  - [Hemochromatosis].

PMID- 11462695
TI  - [Hennekam syndrome].

PMID- 11462696
TI  - [Hereditary motor and sensory neuropathy, LOM type (HMSNL)].

PMID- 11462697
TI  - [Hermaphroditism, true].

PMID- 11462698
TI  - [Herrmann-Pallister-Opitz syndrome].

PMID- 11462699
TI  - [Hirschsprung disease].

PMID- 11462700
TI  - [Histidinemia].

PMID- 11462702
TI  - [Holoprosencephaly].

PMID- 11462701
TI  - [Holocarboxylase synthetase deficiency].

PMID- 11462703
TI  - [Homocystinuria].

PMID- 11462704
TI  - [Huntington disease].

PMID- 11462705
TI  - [Hutterite syndrome, Bowen-Conradi type].

PMID- 11462706
TI  - [Hydrolethalus syndrome].

PMID- 11462707
TI  - [Hypercholesterolemia, familial].

PMID- 11462708
TI  - [Aarskog syndrome].

PMID- 11462709
TI  - [Hyperglycinemia, nonketotic].

PMID- 11462710
TI  - [Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome].

PMID- 11462711
TI  - [Hyperprolinemia].

PMID- 11462712
TI  - [Hypertelorism-hypospadias syndrome].

PMID- 11462713
TI  - [Hypertelorism-microtia-facial cleft-conductive deafness].

PMID- 11462714
TI  - [Hypervalinemia].

PMID- 11462715
TI  - [Hypochondroplasia].

PMID- 11462716
TI  - [Hypodontia-nail dysgenesis].

PMID- 11462717
TI  - [Hypoglossia-hypodactylia].

PMID- 11462718
TI  - [Hypogonadotropic hypogonadism].

PMID- 11462719
TI  - [Aase-Smith syndrome].

PMID- 11462720
TI  - [Hypohidrotic ectodermal dysplasia, X-linked].

PMID- 11462721
TI  - [Hypomandibular faciocranial dysostosis].

PMID- 11462722
TI  - [Hypomelanosis of Ito, pigmentary dysplasia].

PMID- 11462723
TI  - [Hypoparathyroidism, familial].

PMID- 11462724
TI  - [Hypophosphatasia].

PMID- 11462725
TI  - [Hypophosphatemia, non X-linked, X-linked].

PMID- 11462726
TI  - [Hypopigmentation-immune defect, Griscelli type].

PMID- 11462727
TI  - [Hypospadias].

PMID- 11462728
TI  - [Hypothalamic hamartoblastoma syndrome, congenital, Hall-Pallister syndrome].

PMID- 11462729
TI  - [Hypoventilation, congenital central alveolar type].

PMID- 11462730
TI  - [Acetoacetyl-CoA thiolase deficiency, mitochondrial].

PMID- 11462731
TI  - [Acheiropody].

PMID- 11462732
TI  - [Achondrogenesis (Houston-Harris type, Langer-Saldino type, Parenti-Fraccaro
      type)].

PMID- 11462733
TI  - [Achondroplasia].

PMID- 11462734
TI  - [Acidemia, isovaleric].

PMID- 11462735
TI  - [Acidemia, methylmalonic].

PMID- 11462736
TI  - Adults with ADHD. An overview.
AB  - Attention-Deficit Hyperactivity Disorder (ADHD) is a common, genetically
      transmitted neurological disorder, with onset in childhood, probably mediated by
      decreased brain dopaminergic functioning. The first author was one of the
      earliest to describe the persistence of symptoms into adulthood. Prevalence and
      natural history data suggest that of the 3 to 10% of children diagnosed with
      ADHD, one- to two-thirds (somewhere between 1 and 6% of the general population)
      continue to manifest appreciable ADHD symptoms into adult life. This paper
      describes how ADHD in adults can be readily diagnosed and treated, despite
      resembling or coexisting with other psychiatric disorders. The Wender Utah
      diagnostic criteria address adult characteristics of the disorder. Informant and
      patient interviews and rating scales are used to determine the psychiatric status
      of the patient as a child, make a retroactive diagnosis of childhood ADHD, and
      establish the current diagnosis of the adult. Stringent diagnosis is key to
      determining effective treatment. Dopamine agonist stimulant medications appear to
      be the most effective in treating ADHD. About 60% of patients receiving stimulant
      medication showed moderate-to-marked improvement, as compared with 10% of those
      receiving placebo. The core symptoms of hyperactivity, inattention, mood
      lability, temper, disorganization, stress sensitivity, and impulsivity have been
      shown to respond to treatment with stimulant medications. Non-dopaminergic
      medications, such as the tricyclic antidepressants and SSRIs have generally not
      been useful in adults with ADHD in the absence of depression or dysthymia.
      Pemoline is no longer approved for use in these patients, despite early favorable
      reports. Appropriate management of adult patients with ADHD is multimodal.
      Psychoeducation, counseling, supportive problem-directed therapy, behavioral
      intervention, coaching, cognitive remediation, and couples and family therapy are
      useful adjuncts to medication management. Concurrent supportive psychosocial
      treatment or polypharmacy may be useful in treating the adult with comorbid ADHD.

PMID- 11462737
TI  - Continuous performance tests are sensitive to ADHD in adults but lack
      specificity. A review and critique for differential diagnosis.
AB  - Historically, the focus for Attention Deficit Hyperactivity Disorder (ADHD) has
      been on children, with considerable research and many opinions available in this
      area. More recently, the focus has been expanded to include ADHD in adults.
      Assessment of ADHD in adults is complicated by the high rate of co-occurring
      disorders as well as symptom overlap with a number of disorders. One popular
      family of measures for the assessment of attention and executive control is the
      continuous performance test (CPT). A review of the available research on CPTs
      reveals that they are quite sensitive to CNS dysfunction. This is both a strength
      and a limitation of CPTs in that multiple disorders can result in impaired
      performance on a CPT. The high sensitivity of CPTs is further complicated by the
      multiple variations of CPTs available, some of which may be more sensitive or
      demonstrate better specificity to ADHD in adults than others. If CPTs are to be
      used clinically, further research will be needed to answer the questions raised
      by this review.

PMID- 11462738
TI  - Adult ADHD. Analysis of self-ratings on a behavior questionnaire.
AB  - It is customary to acquire behavior ratings of children with ADHD from parents
      and teachers, but comparable informants are typically not available for adults.
      Self-rating is substituted. The present study presents self-ratings of ADHD and
      control adults on a 43-item scale. The groups differed significantly on all but 4
      descriptors, and 3 sufficed to account for more than 50% of the variance,
      reflecting distractibility, impulsivity and lack of control of behavior,
      respectively. Discriminant analysis revealed 83% and 90% correct classification
      of ADHD and controls, respectively. The results support the usefulness of self
      rating in adults with ADHD and corroborate the resemblance and continuity between
      childhood and adult ADHD.

PMID- 11462739
TI  - The diagnosis and neuropsychological assessment of adult attention
      deficit/hyperactivity disorder. Scientific study and practical guidelines.
AB  - The recognition of attention deficit/hyperactivity disorder (ADHD) in adults is a
      well documented, but relatively new development. Investigations of the disorder
      have indicated that disturbances in behavior and adjustment are common. These
      disturbances may be linked to poorly developed executive functions. This paper
      reviews the neuropsychological studies that have compared persons with ADHD to
      normal controls and to psychiatric controls. The review indicates that persons
      with ADHD share many neuropsychological characteristics with other persons with
      serious psychiatric conditions, although those with ADHD may have a particular
      profile of slowed performance in tasks of sustained attention and set shifting,
      and their use of working memory may be particularly impaired. The implications of
      research for clinical assessment are discussed. We contend that a
      neuropsychological orientation is necessary for making the diagnosis and gaining
      a full understanding of adult ADHD. A model for clinical assessment is proposed
      which utilizes a neuropsychological orientation and the targeted administration
      of neuropsychological instruments. The careful use of neuropsychological measures
      is warranted in providing an elaborate picture of a person's functioning,
      although the use of neuropsychological tests is not necessary to make the
      diagnosis.

PMID- 11462740
TI  - A nosology of disorders of attention.
AB  - The trailblazing research on sleep mechanisms and petit mal epilepsy, conducted
      during the period from 1940 through 1970, illuminated the brain substrate for
      normal consciousness and attention, as well as their disorders. This research
      helped inform and structure our neuropsychologically based model of the
      "elements" of attention. The model has been used to assess attention in the
      research laboratory and clinic, and has led to a "nosology of disorders of
      attention," which is presented here in preliminary form. The nosology reviews the
      possible causes of the symptom(s) of impaired attention, as well as suggesting a
      blueprint for future research in this area.

PMID- 11462741
TI  - Attention deficit/hyperactivity disorder as a right hemisphere syndrome.
      Selective literature review and detailed neuropsychological case studies.
AB  - Recent studies of ADHD implicate well-defined neuroanatomical networks and
      neurochemical pathways in its pathophysiological basis. Considerable attention
      has focused on the role of anterior and superior frontal regions and portions of
      the basal ganglia, including the caudate nucleus and globus pallidus. This paper
      reviews a growing literature suggesting differential involvement of right
      hemisphere mechanisms specialized for behavioral regulation and attention.
      Supportive data are drawn from neuropsychology, neuroanatomy, and neurochemistry.
      In addition, three cases are presented that illustrate the complex role of right
      hemisphere dysfunction in adult manifestations of ADHD. We suggest that the
      pleomorphic presentations of ADHD can be understood in terms of a spectrum of
      disturbances in overlapping neural regions, especially involving frontal and
      parietal areas of the right hemisphere and their connections to subcortical
      structures (including the striatum, limbic system and diencephalic nuclei).

PMID- 11462742
TI  - Neurocognitive problems in attention deficit disorder. Alternative concepts and
      evidence for impairment in inhibition of selective attention.
AB  - The critical neurocognitive components of Attention-Deficit/Hyperactivity
      Disorder (ADHD) remain controversial, despite extensive research to disclose the
      essential cognitive components of this disorder. We propose to organize this
      research into three types of cognitive mechanisms while demonstrating the
      consistencies and inconsistencies in each: studies of response inhibition, of
      executive function, and of attentional inhibition. We also present the results of
      cluster analyses of a group (n = 25) of narrowly selected adult patients with
      childhood onset of ADHD, reveal three subtypes of ADHD, and argue that the only
      evidence of a general cognitive deficit is found in tests of selective attention.
      Finally, we provide the results of exploratory studies of selective attention for
      perception and for semantic memories. The data suggest that the cognitive
      disinhibition of ADHD is found in semantic recognition, but not in
      visuoperceptual recognition.

PMID- 11462743
TI  - Comorbidity in adults with attention-deficit/hyperactivity disorder.
AB  - This paper describes the clinical manifestations of attention
      deficit/hyperactivity disorder (ADHD) in adulthood, with particular emphasis
      placed on issues relating to comorbidity. Prospective and retrospective studies
      are reviewed to evaluate the degree to which adults with ADHD exhibit clinical
      features that mirror their childhood counterparts with analogous comorbid
      psychiatric (e.g., antisocial, mood, and anxiety) and/or cognitive (i.e.,
      learning) disorders. We also address the question of whether comorbid disorders
      in adults represent independent diagnostic entities and whether the presence of
      psychiatric comorbidity varies as a function of ADHD subtype (i.e., inattentive,
      hyperactive-impulsive, combined, and residual). As is the case for ADHD in
      childhood, comorbidity is not uncommon among adults with ADHD. However, the
      reported prevalence of comorbid conditions among adults with ADHD varies
      considerably depending upon whether the research used a prospective or
      retrospective design.

PMID- 11462744
TI  - Schizophrenia and attention deficit disorder. Two complex disorders of attention.
AB  - Attentional dysfunction can be found in nearly every form of psychopathology, not
      just in attention deficit disorder (ADD). Being able to distinguish ADD from
      other psychiatric conditions is crucial for clinicians working with adolescents
      and young adults, particularly in the case of psychoses where making the correct
      diagnosis and beginning treatment promptly is extremely important. In this paper
      we review the literature on the attentional dysfunction found in schizophrenia
      and compare it to that found in ADD in an effort to increase our knowledge of
      etiology and underlying mechanisms. Investigators studying ADD may learn from the
      study of schizophrenia by realizing that ADD is also a complex disorder of
      attention that occurs across the developmental spectrum and is characterized by
      various predispositional, environmental, and maturational factors.

PMID- 11462745
TI  - Attention deficit/hyperactivity disorder and substance abuse. Diagnostic and
      therapeutic considerations.
AB  - Patterns of association between attention deficit hyperactivity disorder (ADHD)
      and substance-use disorders are considered. Recent investigations have found that
      up to 50% of individuals with continuing ADHD symptoms have a substance-use
      disorder. ADHD appears to represent an independent risk factor for substance
      abuse. We review clinical challenges posed by the diagnosis of ADHD in substance
      abusing populations. Nicotine dependence is also substantially more common among
      adults with ADHD (40%) than in the general population (26%). While several
      classes of substances of abuse may ameliorate various symptoms of ADHD,
      individuals with ADHD may also be vulnerable to substance use because of poor
      judgment or impulsive behavior in social settings. Evidence is reviewed from
      genetic studies examining the role of the dopamine D2 (DRD2) gene in the etiology
      of ADHD. The presence of ADHD may affect the course of adolescent substance abuse
      in several ways: predicting earlier age of onset, longer duration of substance
      use disorder, and progression of alcohol abuse to another drug-use disorder.
      Individuals with ADHD have been noted to have a shorter interval between the
      onsets of drug abuse and drug dependence. Such individuals are also at greater
      risk for treatment failure, as their disruptive behaviors interfere with
      treatment access and response. Lastly, we review advances in pharmacotherapeutic
      agents used for treating ADHD and consider the impact of these interventions on
      comorbid substance-use disorders. We suggest promising areas of focus for
      clinical research trials targeting the subpopulation of substance abusers with
      concurrent ADHD.

PMID- 11462746
TI  - Attention deficit disorders and sleep/arousal disturbance.
AB  - Many children, adolescents, and adults with Attention Deficit Disorders report
      chronic difficulties with falling asleep, awakening and/or maintaining adequate
      daytime alertness. These problems may be due to a variety of factors, including
      environment, lifestyle, and psychiatric comorbidities. Impairments in
      sleep/arousal may also be related more directly to the underlying pathophysiology
      of ADD. This chapter describes clinical manifestations of sleep/arousal problems
      often associated with ADD and reviews behavioral and medication options for
      treatment.

PMID- 11462747
TI  - Adult ADHD. Controlled medication assessment.
AB  - Many adults with ADHD respond to stimulant therapy, but controlled medication
      assessments have not been reported. We administered an effortful working memory
      task in four half-day sessions, double blind, at methylphenidate levels of 0, 5,
      10 and 20 mg. Dose-response curves were established individually. Fifteen of 17
      patients displayed a favorable response to one or more levels of medication; that
      is, they achieved more correct responses and less variability than on placebo.
      Each dose level elicited optimal performance from some of the patients. Unlike
      monitoring by self-report, the objective medication assessment offers an
      expeditious approximation to the ultimate optimal dose, potentially saving the
      patient weeks on an ineffective and/or excessive dosage regime.

PMID- 11462748
TI  - Psychostimulants in the treatment of adults with psychosis and attention deficit
      disorder.
AB  - Whether conceptualized as comorbid ADD with psychosis or as a distinct diagnostic
      entity--ADD psychosis--patients with features of both ADD and psychosis benefit
      from treatment with psychostimulants. It is hypothesized that psychostimulants
      have their therapeutic effect via amelioration of frontal lobe dysfunction.

PMID- 11462749
TI  - Aspects of psychotherapy with adults with attention deficit disorder.
AB  - The process of psychotherapy with individuals with Attention Deficit Disorder who
      may require this form of intervention (in addition to medication and
      psychoeducation) is described. Salient features of therapy specific to these
      patients, such as the subjective effects of medication, characteristic defensive
      operations, and reconciliation with the past, are emphasized.

PMID- 11462750
TI  - Alternative treatments for adults with attention-deficit hyperactivity disorder
      (ADHD).
AB  - A previous review of alternative treatments (Tx) of ADHD--those other than
      psychoactive medication and behavioral/psychosocial Tx--was supplemented with an
      additional literature search focused on adults with ADHD. Twenty-four alternative
      Tx were identified, ranging in scientific documentation from discrediting
      controlled studies through mere hypotheses to positive controlled double-blind
      clinical trials. Many of them are applicable only to a specific subgroup.
      Although oligoantigenic (few-foods) diets have convincing double-blind evidence
      of efficacy for a properly selected subgroup of children, they do not appear
      promising for adults. Enzyme-potentiated desensitization, relaxation/EMG
      biofeedback, and deleading also have controlled evidence of efficacy. Iron
      supplementation, magnesium supplementation, Chinese herbals, EEG biofeedback,
      massage, meditation, mirror feedback, channel-specific perceptual training, and
      vestibular stimulation all have promising prospective pilot data, many of these
      tests reasonably controlled. Single-vitamin megadosage has some intriguing pilot
      trial data. Zinc supplementation is hypothetically supported by systematic case
      control data, but no systematic clinical trial. Laser acupuncture has promising
      unpublished pilot data and may be more applicable to adults than children.
      Essential fatty acid supplementation has promising systematic case-control data,
      but clinical trials are equivocal. RDA vitamin supplementation, non-Chinese
      herbals, homeopathic remedies, and antifungal therapy have no systematic data in
      ADHD. Megadose multivitamin combinations are probably ineffective for most
      patients and are possibly dangerous. Simple sugar restriction seems ineffective.
      Amino acid supplementation is mildly effective in the short term, but not beyond
      2-3 months. Thyroid treatment is effective in the presence of documented thyroid
      abnormality. Some alternative Tx of ADHD are effective or probably effective, but
      mainly for certain patients. In some cases, they are the Tx of choice, and
      initial evaluation should consider the relevant etiologies. A few have failed to
      prove effective in controlled trials. Most need research to determine whether
      they are effective and/or to define the applicable subgroup. Some of them,
      although not safer than standard Tx, may be preferable for an etiologic subgroup.

PMID- 11462751
TI  - Brain imaging of attention deficit/hyperactivity disorder.
AB  - Advances in imaging technology allow unprecedented access to the anatomy and
      physiology of the living, growing human brain. Anatomical imaging studies of
      individuals with attention deficit/hyperactivity disorder (ADHD) consistently
      point to involvement of the frontal lobes, basal ganglia, corpus callosum, and
      cerebellum. Imaging studies of brain physiology also support involvement of right
      frontal-basal ganglia circuitry with a powerful modulatory influence from the
      cerebellum. Although not currently of diagnostic utility, further extension and
      refinement of these findings may offer hope for greater understanding of the core
      nature of ADHD and possible subtyping to inform treatment interventions.

PMID- 11462752
TI  - EEG biofeedback treatment of ADD. A viable alternative to traditional medical
      intervention?
AB  - Literature searches dating back to 1968 were conducted through Psychlit and
      Medline services to review the scientific literature on EEG biofeedback treatment
      of ADD. While anecdotal and case reports cite promising evidence, methodological
      problems coupled with a paucity of research precludes any definitive conclusions
      as to the efficacy of enhanced alpha and hemisphere-specific EEG biofeedback
      training. One of the more promising EEG biofeedback treatment paradigms involves
      theta/beta training. Studies have reported that academic, intellectual, and
      behavioral gains have been attained with this approach. Significant behavioral
      and cognitive changes have also been reported following SMR training. However,
      research into these treatment approaches has also been marred by methodological
      inadequacies and lack of sufficient follow-up studies. A number of
      recommendations for future research into this treatment approach are made.

PMID- 11462753
TI  - Improving attention and managing attentional problems. Adapting rehabilitation
      techniques to adults with ADD.
AB  - Research and clinical experience in the field of brain injury rehabilitation have
      focused quite extensively on the need and potential to retrain attentional skills
      that are commonly affected by acquired brain injury. Four approaches to managing
      attention impairments that have emerged from this literature include attention
      process training, training use of strategies and environmental support, training
      use of external aids, and the provision of psychosocial support. Most often,
      several of these will be used in combination. For example, a therapy regimen
      might include attention process training emphasizing specific components of
      attention (e.g., sustained attention), in conjunction with training in pacing
      techniques, and psychosocial support, where the client keeps behavioral logs and
      discusses insights gained from tracking attention successes and attention lapses.
      Although there are as yet little data with regard to the effectiveness of these
      approaches in adults with developmental disorders of attention, there is a
      growing literature suggesting they may be effective in children and adolescents
      with ADHD. Further investigation of the application of such techniques in adults
      with a wide variety of attention disorders, including developmental disorders,
      would be valuable.

PMID- 11462754
TI  - Metacognitive remediation in adult ADHD. Treating executive function deficits via
      executive functions.
AB  - The neuropathology underlying ADHD most consistently points to dysfunction in
      corticostriatal pathways--leading to inactivation, or insufficient engagement, of
      frontal and prefrontal lobes. By implication there may be functional
      disconnection between the anterior and posterior higher cortical regions, instead
      of a fixed dysfunction in either one. Given this premise, reconnection of these
      systems via cognitive interventions constitutes a logical remedial approach in
      the treatment of ADHD, which this paper introduces. In particular, a hybrid model
      is developed which proposes integration of existing psychodynamic, cognitive, and
      neuropsychological interventions. An organizing theme is expansion of
      metacognitive understanding through these procedures, powerfully exemplified via
      use of metaphor in clinical vignettes.

PMID- 11462755
TI  - College students with ADHD and other hidden disabilities. Outcomes and
      interventions.
AB  - Nearly 25 years of special education law have enabled many qualified students
      with disabilities to graduate from college preparatory high school programs and
      enter institutes of higher education. The Americans with Disabilities Act enacted
      by Congress in 1990, the Individuals with Disabilities Education Act of 1975, and
      Section 504 of the Rehabilition Act of 1973 all mandate special education
      services for students with disabilities. A parallel nationwide rise is being
      reported in the numbers of students with disabilities on college campuses. The
      greatest increase is seen in students with so-called hidden disabilities such as
      learning disabilities, ADHD, and psychiatric disabilities. These students face a
      number of obstacles once they are admitted to college. Many factors, some
      intrinsic to the student and others extrinsic to the campus, moderate success in
      higher education. Overlapping or multiple diagnoses, psychological distress, poor
      social and interpersonal skills, persisting cognitive deficits (especially in the
      area of executive functioning), and alcohol abuse are important factors that must
      be understood as institutions of higher education strive to promote access and
      provide effective support services on their campuses.

PMID- 11462756
TI  - Adult ADHD. Concluding thoughts.
AB  - This concluding paper raises some final questions and issues that the authors
      feel should receive more emphasis in future research on ADHD in adults. One
      significant problem for our field is the upward extension of child-based models
      and approaches without proper adaptation to adults. With adults differing
      patterns of comorbidity and symptom heterogeneity pose new conceptual,
      diagnostic, and treatment challenges. As an illustration, we review ten common
      presenting complaints in adults and their link to the underlying core ADHD
      deficits of hyperkinesis, inattention, and impulsivity. While these core symptoms
      are often overt problems in children, in adults subtler executive dysfunction
      appears. Even though the growing consensus is that ADHD is a disorder of
      executive functions (EF), the details of the EF/ADHD connection remain unclear
      and may be far more complex in adults. That complexity is mirrored in the
      widening anatomic representation of EF, extending beyond the frontal lobes into
      the subcortex and other nonfrontal regions. More research will be needed to
      follow the developmental trajectory of executive dysfunction in ADHD over the
      life cycle and tie this to the developmental neuropsychology of EF. Psychosocial
      context and nongenetic familial influence are also critical variables that need
      greater consideration when characterizing and measuring ADHD symptoms in adults.
      Finally, until we have reached consensus on adult subject selection, we may not
      be able to enhance diagnostic rigor or expand our conceptual framework for
      understanding the underlying pathophysiology of ADHD in adults.

PMID- 11462757
TI  - Clinical and molecular genetics of ADHD and Tourette syndrome. Two related
      polygenic disorders.
AB  - ADHD is a polygenic disorder due to the additive effect of genes affecting
      dopamine, norepinephrine, serotonin, GABA, and other neurotransmitters. Some of
      the specific loci involved are dopamine genes--DRD2, DRD4, DRD5, and the dopamine
      transporter; norepinephrine (NE) and epinephrine (EPI) genes--dopamine beta
      hydroxylase, ADRA2A, ADRA2C, PNMT, norepinephrine transporter, MAOA, COMT;
      serotonin genes--TDO2, HTR1A, HTR1DA, serotonin transporter; GABA genes--GABRB3;
      androgen receptor and other genes. This model is consistent with all of the
      present knowledge about ADHD including (a) the increased frequency of ADHD in the
      relatives of ADHD probands, (b) the presence of a wide spectrum of comorbid
      behaviors (depression, anxiety, learning, conduct, oppositional-defiant, conduct
      and substance abuse disorders) in ADHD probands and their relatives on both
      parental sides, (c) the close relationship to Tourette syndrome (TS), (d) the
      failure to find the genes for TS using linkage analysis, (e) the brain imaging
      studies showing hypometabolism of the frontal lobes, (f) the relationship between
      dopamine D2 receptor density and regional blood flow, (g) the correlation between
      tics and dopamine D2 receptor density in TS, (h) the motor hyperactivity of
      dopamine transporter and dopamine D3 receptor gene knockout mice, (i) the LeMoal
      and Shaywitz dopamine deficiency animal models of ADHD, (j) the NE models of
      ADHD, (k) the failure to explain ADHD on the basis of any single neurotransmitter
      defect, (l) the response of ADHD to dopamine and alpha 2-adrenergic agonists, (m)
      the small percentage of the variance of specific behaviors accounted for by each
      gene, and numerous other aspects of ADHD. The implications of the polygenic model
      for the understanding, diagnosis and treatment of ADHD and TS, as well as other
      psychiatric disorders, are reviewed.

PMID- 11462758
TI  - ADHD, aggression, and antisocial behavior across the lifespan. Interactions with
      neurochemical and cognitive function.
AB  - The progression to adult antisocial behavior is the least desirable developmental
      trajectory for children with ADHD. An unremitting pattern of physical aggression
      appears of great import when predicting long-term outcome. However, a profile
      characterized by behavioral and cognitive impulsivity and emotional lability may
      indicate a greater likelihood of the progression to adult antisocial behavior and
      violent impulse-control disorders. This constellation of behaviors appears to be,
      at least in part, mediated by brain serotonergic systems. The contribution of
      cognitive impairments, as manifested by executive function deficits, diminished
      moral reasoning, and impaired empathic ability, to the emergence and persistence
      of antisocial behavior has yet to be discerned.

PMID- 11462759
TI  - Medical mimics. Medical and neurological conditions simulating ADHD.
AB  - The medical and neurological conditions that simulate ADHD are reviewed, as well
      as those disorders frequently presenting as comorbidities with ADHD. The
      localization of ADHD has invoked multiple areas, including frontal lobes,
      nondominant parietal lobe, and basal ganglia, and the neural network theory of
      cortical-subcortical-cortical loops has been implicated in the pathogenesis of
      ADHD. The medical evaluation of patients presenting with ADHD should be
      comprehensive, with an emphasis on demonstrating chronic and permeating symptoms
      since early childhood without a better medical explanation. Associated thyroid
      disorders are reviewed, including the syndrome of resistance to thyroid hormone.
      Suggested laboratory studies are provided, depending on the clinical
      circumstances.

PMID- 11462760
TI  - Quinolinic acid accumulation during neuroinflammation. Does it imply
      excitotoxicity?
AB  - It is often proposed that quinolinic acid (QUIN) contributes to the
      pathophysiology of neuroinflammation because this kynurenine pathway metabolite
      is a selective agonist of N-methyl-D-aspartate (NMDA) receptors, and both its
      brain tissue and cerebrospinal fluid concentrations increase markedly with
      inflammation. However, whether or not the extracellular levels of QUIN reached
      during neuroinflammation are high enough to promote excitotoxicity, remains
      unclear because QUIN is a weak NMDA receptor agonist. We have addressed this
      issue by evaluating the extracellular concentrations of QUIN that must be reached
      to initiate potentially excitotoxic changes in the cerebral cortex of rats, under
      normal conditions, and when superimposed on another insult. We have also examined
      the increase in extracellular lactate associated with the perfusion of increasing
      concentrations of QUIN through a microdialysis probe. The extracellular EC50 for
      induction of local depolarisation was 228 microM with QUIN alone; that is, about
      30 times the levels of QUIN measured previously in immune activated brain.
      Furthermore, at least 20 microM extracellular QUIN needed to be reached to reduce
      K+ induced spreading depression, an unexpected effect since spreading depression
      is inhibited by NMDA receptor antagonists. Our data suggest that, although
      synthesis of QUIN from activated microglia and invading macrophages can increase
      its extracellular concentration 10-100-fold, the levels that are reached in these
      conditions remain far below the concentrations of QUIN that are necessary for
      excessive NMDA receptor activation. However, the possibility that QUIN
      accumulation may be a deleterious feature of neuroinflammation cannot be ruled
      out at this stage.

PMID- 11462761
TI  - Monitoring for neuroprotection. New technologies for the new millennium.
AB  - Monitoring for neuroprotection, like surgery, has placed on emphasis on minimal
      or non-invasiveness. Monitoring of parameters that truly reflect the degree of
      injury to the nervous system is another goal. Thus, two themes for the coming
      decade in neuromonitoring will be: (1) less-invasive monitoring; and (2)
      parameters that more closely reflect the etiological factors in ischemic or other
      neuroinjury. In this paper, we review neuromonitoring techniques and devices that
      can be used readily in the operating room or intensive care unit setting. Those
      that require transport of the patient to a special facility (e.g., for computed
      tomography or magnetic resonance imaging/spectroscopy) and those that have been
      in standard practice for neuromonitoring (e.g., electrophysiological monitoring-
      EEG, evoked potentials) are not considered. The two techniques considered in
      detail are (1) continuous multiparameter local brain tissue monitoring with
      microprobes, and (2) non-invasive continuous local brain tissue oxygenation
      monitoring by near infrared spectroscopy. Both techniques have been cleared by
      the Food and Drug Administration (FDA) for clinical use. The rationale for their
      use, the nature of the devices, and clinical results to date are reviewed. It is
      expected that both techniques will gain wide acceptance during the coming decade;
      further advances in neuromonitoring that can be expected further into the twenty
      first century are also discussed.

PMID- 11462762
TI  - Neuronal protein kinase signaling cascades and excitotoxic cell death.
AB  - Perturbation of normal survival mechanisms may play a role in a large number of
      disease processes. Glutamate neurotoxicity, particularly when mediated by the N
      methyl-D-aspartate (NMDA) subtype of glutamate receptors, has been hypothesized
      to underlie several types of acute brain injury, including stroke. Several
      neurological insults linked to excessive release of glutamate and neuronal death
      result in tyrosine kinase activation, including p44/42 mitogen activated protein
      (MAP) kinase. To further explore a role for MAP kinase activation in
      excitotoxicity, we used a novel tissue culture model to induce neurotoxicity.
      Removal of the endogenous blockade by Mg2+ of the NMDA receptor in cultured
      hippocampal neurons triggers a self perpetuating cycle of excitotoxicity, which
      has relatively slow onset, and is critically dependent on NMDA receptors and
      activation of voltage gated Na+ channels. These injury conditions led to a rapid
      phosphorylation of p44/42 that was blocked by MAP kinase kinase (MEK) inhibitors.
      MEK inhibition was associated with protection against synaptically mediated
      excitotoxicity. Interestingly, hippocampal neurons preconditioned by a sublethal
      exposure to Mg(2+)-free conditions were rendered resistant to injury induced by a
      subsequently longer exposure to this insult; the preconditioning effect was MAP
      kinase dependent. The MAP kinase signaling pathway can also promote polypeptide
      growth factor mediated neuronal survival. MAP kinase regulated pathways may act
      to promote survival or death, depending upon the cellular context in which they
      are activated.

PMID- 11462763
TI  - Neuroprotection for the new millennium. Matchmaking pharmacology and technology.
AB  - A major theme of the 1990s in the pathophysiology of nervous system injury has
      been the multifactorial etiology of irreversible injury. Multiple causes imply
      multiple opportunities for therapeutic intervention--hence the abandonment of the
      "magic bullet" single pharmacologic agent for neuroprotection in favor of
      pharmacologic "cocktails". A second theme of the 1990s has been the progress in
      technology for neuroprotection, minimally- or non-invasive monitoring as well as
      treatment. Cardiac stenting has eliminated the need, in many cases, for open
      heart surgery; deep brain stimulation for Parkinson's disease has offered
      significant improvement in quality of life for many who had exhausted cocktail
      drug treatment for their disease. Deep brain stimulation of the subthalamic
      nucleus offers a novel treatment for Parkinson's disease where a technological
      advance may actually be an intervention with effects that are normally expected
      from pharmacologic agents. Rather than merely "jamming" the nervous system
      circuits involved in Parkinson's disease, deep brain stimulation of the
      subthalamic nucleus appears to improve the neurotransmitter imbalance that lies
      at the heart of Parkinson's disease. It may also slow the progression of the
      disease. Given the example of deep brain stimulation of the subthalamic nucleus
      for Parkinson's disease, in future one may expect other technological or
      "hardware" interventions to influence the programming or "software" of the
      nervous system's physiologic response in certain disease states.

PMID- 11462765
TI  - The role of intraoperative neurophysiology in the protection or documentation of
      surgically induced injury to the spinal cord.
AB  - Playing both neuroprotective and educational roles, intraoperative
      neurophysiology has become an intrinsic part of modern neurosurgery. In this
      article, we present evidence substantiating the neuroprotective role of
      intraoperative neurophysiology, specifically its capacity to help prevent injury
      to the corticospinal tracts and the dorsal columns during spinal cord injury.

PMID- 11462764
TI  - Neuroprotective role of neurophysiological monitoring during endovascular
      procedures in the spinal cord.
AB  - The endovascular treatment of spinal vascular malformations places the spinal
      cord at risk for ischemia. When these procedures are performed using general
      anesthesia, the neurophysiological monitoring methods currently available provide
      the only means by which to assess the functional integrity of sensory and motor
      pathways. Neurophysiological monitoring allows a warning for the neuroradiologist
      of impending irreversible neurological damage so that action may be taken for the
      prompt restoration of adequate spinal cord perfusion. Muscle motor evoked
      potentials (mMEPs) better reflect spinal cord perfusion in the anterior spinal
      artery territory than do somatosensory evoked potentials (SEPs), although their
      use during spinal endovascular procedures remains anecdotal in the literature. In
      the study reported here we assessed: (1) the feasibility of intraoperative
      neurophysiological monitoring, (2) the role of provocative tests with Amytal and
      Xylocaine, and (3) the specific but complementary role played by SEPs and mMEPs,
      during endovascular embolization of spinal vascular malformations and tumors. The
      results suggest that: (1) neurophysiological monitoring is feasible during most
      endovascular procedures in the spine and spinal cord under general anesthesia,
      (2) provocative tests enhance the safety of the procedure, (3) mMEPs are more
      feasible than SEPs and more sensitive than SEPs to provocative tests. We strongly
      suggest the use of multimodal neurophysiological monitoring and provocative tests
      during the endovascular treatment of spinal and spinal cord vascular lesions.

PMID- 11462767
TI  - Neuroprotective effects of novel cholinesterase inhibitors derived from
      rasagiline as potential anti-Alzheimer drugs.
AB  - TV3326, (N-propargyl-(3R)-aminoindan-5-yl-ethyl,methyl carbamate) was prepared in
      order to combine the neuroprotective effects of rasagiline, a selective inhibitor
      of monoamine oxidase (MAO)-B with the cholinesterase (ChE) inhibitory activity of
      rivastigmine as a potential treatment for Alzheimer's disease. The study reported
      here examined the neuroprotective effects of TV3326 against various insults in
      vitro and in vivo. TV3326 caused a dose related (10-500 microM) reduction in
      death induced in NGF differentiated rat pheochromocytoma (PC12) cells by 3-4 hour
      exposure to oxygen-glucose deprivation. A single s.c. injection of TV3326 given
      five minutes after closed head injury in mice significantly reduced the cerebral
      edema, and accelerated the recovery of motor function and spatial memory several
      days later. Unilateral icv injection of streptozotocin (STZ) 1.5 mg in rats,
      caused specific damage to myelinated neurones in the fornix and corpus callosum
      accompanied by microgliosis. Three bilateral injections of STZ, 0.25 mg each,
      caused more widespread damage, and a marked impairment in spatial memory. Chronic
      oral treatment with TV3326 (75 mumols/kg) reduced the neuronal damage and
      microgliosis and almost completely prevented the memory impairment. The
      neuroprotective effect in PC12 cells may be due to a combination of ChE
      inhibition and antiapoptotic activity. The latter does not result from ChE
      inhibition. It is associated with the presence of the propargyl group, since it
      occurs with other propargylamines that do not inhibit MAO, but not with drugs
      that inhibit only ChE.

PMID- 11462768
TI  - The action of acetyl-L-carnitine on the neurotoxicity evoked by amyloid fragments
      and peroxide on primary rat cortical neurones.
AB  - The amyloid beta-peptides have been implicated in the excitotoxic mechanism of
      neuronal injury in the pathogenesis of Alzheimer's disease. In this paper we
      examine the effect of different amyloid fragments (beta A1-40, A1-28, and A25
      35), as well as potential neuroprotective compounds on rat cortical neuron
      viability. Exposure of neurones to beta A25-35 or A1-40 at concentrations as low
      as 1 microgram/ml inhibited, significantly, the MTT response and this level of
      inhibition was similar after 24-h or three-day exposure. Furthermore, the level
      of inhibition was not affected by the presence or absence of 5% horse serum in
      the medium. Preexposure (10 min) of neurones to ALC at concentrations of 0.1, 1,
      5, and 10 mM attenuated the inhibition of the MTT response caused by beta A25-35
      (50 micrograms/ml) in serum free medium for 24 h. The treatment of cells with
      vitamin E (100 microM), catalase (4 mg/ml), NGF (0.1 and 10 ng/ml), or
      cycloheximide (0.1 microgram/ml) significantly restored the MTT response that was
      inhibited by beta A25-35. The mechanism for the protective actions of these
      compounds against beta A25-35 toxicity is not clear but may involve free radical
      scavenger action and preservation of energy production, although other
      mechanisms, especially for ALC, such as a direct effect on A-beta interaction
      with charged anionic phospholipids and/or stabilizing action on membranes, are
      also possible.

PMID- 11462769
TI  - Post-stroke dementia. Nootropic drug modulation of neuronal nicotinic
      acetylcholine receptors.
AB  - Nefiracetam is a new pyrrolidone nootropic drug that is being developed for
      clinical use in the treatment of post-stroke vascular-type and Alzheimer's-type
      dementia. Among a few neuroreceptors that have been identified as potential
      targets of nootropics, neuronal nicotinic acetylcholine receptors (nnAChRs) are
      deemed the most important since they are related to learning, memory, and
      Alzheimer's disease dementia. We have recently found potent stimulating action of
      nefiracetam on nnAChRs. Rat cortical neurons in long-term primary culture
      expressed nnAChRs. Whole-cell patch clamp experiments revealed two types of
      currents induced by ACh, alpha-bungarotoxin (alpha-BuTX)-sensitive, rapidly
      desensitizing, alpha 7-type currents and alpha-BuTX-insensitive, slowly
      desensitizing, alpha 4 beta 2-type currents. Although alpha 7-type currents were
      only weakly inhibited by nefiracetam, alpha 4 beta 2-type currents were potently
      and efficaciously potentiated by nefiracetam. Nefiracetam at 0.1 nM reversibly
      potentiated ACh-induced currents to 200-300% of control. Very high concentrations
      (about 10 microM) also potentiated these currents, but to a lesser extent,
      indicative of the bell-shaped dose-response relationship known to occur for
      nefiracetam, even in animal behavior experiments. Three specific inhibitors of
      each of PKA and PKC did not prevent nefiracetam from potentiating ACh-induced
      currents, indicating that these protein kinases are not involved in nefiracetam
      action. Pretreatment with pertussis toxin did not alter nefiracetam potentiation,
      indicating Gi/Go proteins are not involved. Pretreatment with cholera toxin did
      abolish nefiracetam potentiation. Thus, nefiracetam potentiation is mediated via
      Gs proteins. In conclusion, nefiracetam stimulates alpha 4 beta 2-type nnAChRs
      via Gs proteins at nanomolar concentrations. The potentiation of alpha 4 beta 2
      type nnAChRs is thought to be at least partially responsible for cognitive
      enhancing action.

PMID- 11462771
TI  - Antioxidant and antiaging activity of N-acetylserotonin and melatonin in the in
      vivo models.
AB  - It is generally accepted that antioxidant properties of melatonin significantly
      contribute to its antiaging effect. Antioxidant effects of N-acetylserotonin
      (NAS), a melatonin precursor and metabolite, might predict its antiaging action
      as well. The antiaging effect of NAS was studied in female retired breeders and
      male C3H mice. Both NAS and melatonin administered with drinking water prolonged
      life span in male animals by about 20% versus control animals (p < 0.01) but did
      not affect the life span of female mice. Antioxidative activity was evaluated by
      determining the malonaldehyde + 4-hydroxynonenal (MDA + 4-HNE) and cellular
      glutathion peroxidase (GPx) levels in male, 11-month-old, C57Bl/6J mice with very
      limited (if any) capacity to convert pineal NAS into melatonin. NAS increased the
      antioxidant capacity of kidney. Both NAS and melatonin (four weeks daily i.p.
      injections) increased the antioxidant capacity of brain as demonstrated by
      decreased MDA + 4-HNE and increased GPx levels. NAS-treated C57Bl/6J mice
      experienced a weight loss of 9%, whereas the saline and melatonin groups only 3%.
      NAS- and melatonin-treated animals had healthy and luxuriant fur coats with some
      gray fur in the melatonin group; animals in the saline group had large areas of
      baldness. This study demonstrates, for the first time, the antiaging effect of
      NAS. This effect needs to be confirmed in animals with impaired capacity to
      convert NAS into melatonin.

PMID- 11462772
TI  - Free radical-mediated molecular damage. Mechanisms for the protective actions of
      melatonin in the central nervous system.
AB  - This review briefly summarizes the multiple actions by which melatonin reduces
      the damaging effects of free radicals and reactive oxygen and nitrogen species.
      It is well documented that melatonin protects macromolecules from oxidative
      damage in all subcellular compartments. This is consistent with the protection by
      melatonin of lipids and proteins, as well as both nuclear and mitochondrial DNA.
      Melatonin achieves this widespread protection by means of its ubiquitous actions
      as a direct free radical scavenger and an indirect antioxidant. Thus, melatonin
      directly scavenges a variety of free radicals and reactive species including the
      hydroxyl radical, hydrogen peroxide, singlet oxygen, nitric oxide, peroxynitrite
      anion, and peroxynitrous acid. Furthermore, melatonin stimulates a number of
      antioxidative enzymes including superoxide dismutase, glutathione peroxidase,
      glutathione reductase, and catalase. Additionally, melatonin experimentally
      enhances intracellular glutathione (another important antioxidant) levels by
      stimulating the rate-limiting enzyme in its synthesis, gamma-glutamylcysteine
      synthase. Melatonin also inhibits the proxidative enzymes nitric oxide synthase
      and lipoxygenase. Finally, there is evidence that melatonin stabilizes cellular
      membranes, thereby probably helping them resist oxidative damage. Most recently,
      melatonin has been shown to increase the efficiency of the electron transport
      chain and, as a consequence, to reduce election leakage and the generation of
      free radicals. These multiple actions make melatonin a potentially useful agent
      in the treatment of neurological disorders that have oxidative damage as part of
      their etiological basis.

PMID- 11462774
TI  - Neuroprotective and cognition-enhancing properties of MK-801 flexible analogs.
      Structure-activity relationships.
AB  - Neuroprotective and biobehavioral properties of a series of novel open chain MK
      801 analogs, as well as their structure-activity relationships have been
      investigated. Three groups of compounds were synthesized: monobenzylamino,
      benzhydrylamino, and dibenzylamino (DBA) analogs of MK-801. It was revealed that
      DBA analogs exhibit pronounced glutamate-induced calcium uptake blocking
      properties and anti-NMDA activity. The hit compound of DBA series, NT-1505, was
      investigated for its ability to improve cognition functions in animal model of
      Alzheimer's disease type dementia, simulated by treating animals with
      cholinotoxin AF64A. The results from an active avoidance test and a Morris water
      maze test showed that experimental animals, treated additionally with NT-1505,
      exhibited much better learning ability and memory than the control group (AF64A
      treated) and close to that of the vehicle group of animals (treated with
      physiological solution). Study of NT-1505 influence on locomotor activity
      revealed that it is characterized by a spectrum of behavioral activity radically
      different from that of MK-801, and in contrast to the latter one does not produce
      any psychotomimetic side effects in the therapeutically significant dose
      interval. The computed docking of MK-801 and its flexible analogs on the NMDA
      receptor elucidated the crucial role of the hydrogen bond formed between these
      compounds and the asparagine residue for magnesium binding in the NMDA receptor.
      It was suggested that strong hydrophobic interaction between MK-801 and the
      hydrophobic pocket in the NMDA receptor-channel complex determines much higher
      irreversibility of this adduct compared to the intermediates formed between this
      site and Mg ions or flexible DBA derivatives, which might explain the absence of
      PCP-like side effects of the latter compounds.

PMID- 11462775
TI  - Amino acid uptake and release in primary astrocyte cultures exposed to ethanol.

PMID- 11462776
TI  - Synaptic deprivation and age-related vulnerability to hypoxic-ischemic neuronal
      injury. A hypothesis.
AB  - Advanced age is associated with physiological changes, such as cerebral
      autoregulation dysfunction, atrial fibrillation, reduced cerebral blood flow,
      elevated blood pressure, and other changes. Stroke-related dementia is associated
      with brain loss principally due to strokes, and neuropathological examination of
      the brains of old people shows a direct correlation between the extent of brain
      loss and dementia. However, the exact mechanism of the age related vulnerability
      to hypoxic-ischemic neuronal injury remains unknown. The majority of synapses in
      the brain use excitatory amino acids as their neurotransmitter. Glutamate, a
      major endogenous excitatory amino acid required for normal physiological
      excitation, is also involved in the pathophysiology of hypoxic-ischemic neuronal
      injury. The N-methyl-D-aspartate (NMDA) glutamate receptor subtype plays a major
      role in mediating hypoxic-ischemic neuronal injury. NMDA receptors also mediate
      adaptive responses important for synaptic plasticity. This report explores the
      possible role of synaptic activity as a protective mechanism against neuronal
      cell death. Specifically, the role of NMDA receptors in neuronal plasticity by
      upregulating a survival pathway is discussed. Loss of a neuronal population that
      uses glutamate as its neurotransmitter leads to a loss of activity on the
      postsynaptic neurons or synaptic deprivation. Deprivation of excitatory amino
      acids on the postsynaptic neurons results in the failure of activity-dependent
      induced intrinsic survival pathways induced by NMDA receptors. The loss of
      neuroprotective intrinsic survival pathways increases the vulnerability of these
      neurons to more hypoxic-ischemic neuronal damage. Since cerebral infarction is
      also age related, this hypothesis provides a plausible explanation of how we
      become more vulnerable to hypoxic-ischemic neuronal injury as a function of age.

PMID- 11462778
TI  - The failure of neuronal protective agents versus the success of thrombolysis in
      the treatment of ischemic stroke. The predictive value of animal models.
AB  - Agents claimed to be neuroprotective in animal stroke models have all failed in
      human trials. Thrombolysis has been reported as beneficial in animal and human
      stroke. We explore the reasons for this disparity, using a review of published
      results of agents tested both in animal stroke models and in human stroke trials.
      In animals the effect of neuroprotective agents and of thrombolytic agents on
      infarct size is time-dependent: early initiation of treatment works best; and
      benefit is progressively--and eventually totally--lost with increasing delay of
      time of first treatment. The animal data also show that, overall, the beneficial
      effects of the neuroprotective agents are weaker, and are totally lost sooner,
      than those of thrombolytics. The human data show that the failed trials of the
      neuroprotective agents had entry windows that went far beyond the windows of
      (any) success seen in tests of these agents in animals. By contrast, human
      thrombolysis trials uniformly restricted time of entry to windows in which these
      agents have shown beneficial effect in animals. In clinical stroke trials,
      neuroprotective agents failed to produce benefit because their effects at best
      are too weak, and they were used at times predictable from the animal models as
      too late. Thrombolytic therapy, which has a stronger effect than neuroprotective
      agents in animal models, was used clinically during the early window of optimal
      effectiveness, and produced beneficial results. "Too little/too late" is the
      recipe for failure in the treatment of ischemic stroke.

PMID- 11462779
TI  - Low molecular weight heparin and the treatment of ischemic stroke. Animal
      results, the reasons for failure in human stroke trials, mechanisms of action,
      and the possibilities for future use in stroke.

PMID- 11462780
TI  - Non-pharmacologic (physiologic) neuroprotection in the treatment of brain
      ischemia.
AB  - Clinical trials for ischemic stroke have been characterized by a disappointing
      series of negative results, using a panoply of pharmacologic agents. This paper
      emphasizes five physiologic measures that can be taken to mitigate ischemic brain
      damage. These are (1) hypothermia, (2) insulin, (3) arterial hyperoxemia, (4)
      blood pressure control and (5) magnesium. Hypothermia is protective in both focal
      and global ischemia, even postischemically protecting against selective neuronal
      necrosis and infarction. The total equation for protection includes the (i)
      postischemic delay, (ii) depth, and (iii) duration of hypothermia. Insulin
      operates by lowering glucose levels to the normal range in focal ischemia. It is
      possible that very low glucose levels are detrimental in focal ischemia with
      paradoxical augmentation of the infarct size, and that spreading depression plays
      a role in this. Controlled arterial hyperoxemia seems effective experimentally in
      reducing infarct size, operating mechanistically by either a direct effect of
      oxygen, or vasoconstriction causing shunting of blood into the infarct, or both.
      Blood pressure is a critical determinant of infarct size, and raising blood
      pressure improves collateral blood flow and reduces stroke size. To be used
      clinically, however, hemorrhage must be ruled out. The most dramatic clinical
      effects of blood pressure are seen in aneurysm patients with vasospasm, where
      minor increases in blood pressure reverse temporary hemiparesis by reducing
      ischemia. Magnesium is likely the safest NMDA antagonist, with a long history of
      safe administration to pregnant women with eclampsia. There is potential
      interaction with insulin, in that magnesium causes hyperglycemia, which requires
      insulin to counteract it. Magnesium and insulin together have been shown
      effective in experimental brain ischemia. In the absence of safe and effective
      pharmacologic neuroprotection agents, clinical trials should be designed and
      launched to test these physiologic measures, singly and in combination, to reduce
      brain damage after ischemia.

PMID- 11462782
TI  - T2-weighted MRI correlates with long-term histopathology, neurology scores, and
      skilled motor behavior in a rat stroke model.
AB  - The intraluminal suture model of transient middle cerebral artery occlusion
      (MCAO) in the Sprague Dawley strain of rats characteristically results in an
      inconsistently sized brain lesion. The purpose of the investigation reported here
      was to determine whether there were strong point-to-point correlations between
      the degree of cortical lesion size, as assessed in vivo using T2-weighted
      magnetic resonance imaging (MRI) and corresponding cortical lesion size using
      routine histopathological techniques. Moreover, we aimed to investigate if
      cortical lesion size as determined by these two modalities correlates with
      neurological and/or skilled motor deficits observed in individual animals.
      Baseline behavioral scores were obtained on the animals prior to receiving 60 min
      of transient MCAO. Following MCAO, animals were tested for 1-21 days for
      neurological deficits. T2-weighted MRIs of the cortex were taken at two and seven
      days post-MCAO. At 30 and 60 days the rats were retested for forelimb dexterity
      in the staircase test. Subsequently, the cortex was examined for
      histopathological damage. Indeed, there were highly significant correlations
      between lesion size determined by MRI and histopathology. The degree of cortical
      damage observed in the T2-weighted MRI, as well as the size of the
      histopathological lesions were, in turn, highly correlated with the degrees of
      deficiencies observed in the composite neurological assessments and with the
      deficits involving skilled use of the contralateral forepaw (damaged side).

PMID- 11462783
TI  - On the relationship between plasma concentrations of drugs and outcome of stroke
      studies in laboratory animals.
AB  - In assessing plasma concentrations of drugs in relation to neuroprotective
      effect, emphasis should be placed on measured or calculated concentrations during
      the window of opportunity for effect, rather than at the end of the experiment.
      Unbound (plasma free) concentrations should be especially considered as should
      brain penetration to the stroked area. Problem-solving exercises should include
      post hoc assessment of dosing residues and proof of exposure. The shape of the
      graph of response versus concentration in plasma is very steep, giving the
      impression of an all-or-none effect. Although higher doses lead to greater
      effects, attempts to statistically correlate plasma level and infarct size are
      likely to be unsuccessful. There is strong evidence that the pharmacokinetic
      properties of drugs are affected by the physiological consequences of ischemia.

PMID- 11462784
TI  - Combination therapy stroke trial. rt-PA +/- lubeluzole.

PMID- 11462786
TI  - Rat model of autism spectrum disorders. Genetic background effects on Borna
      disease virus-induced developmental brain damage.

PMID- 11462787
TI  - Antiapoptotic properties of rasagiline, N-propargylamine-1(R)-aminoindan, and its
      optical (S)-isomer, TV1022.
AB  - Rasagiline and structurally related propargylamines protected dopaminergic SH
      SY5Y cells from apoptosis induced by 6-OHDA and peroxynitrite-generating SIN-1.
      It was suggested that the intracellular mechanism of the neuroprotection is
      related to the stabilization of mitochondrial membrane potential, as indicated by
      use of a fluorescent indicator, JC-1. The opening of the permeability transition
      pore (PTP) was prevented by rasagiline, even in isolated mitochondria. The
      activation of apoptotic cascade by the oxidative stress and neurotoxins, such as
      activation of caspase 3 and DNA fragmentation, was also inhibited by pretreatment
      with rasagiline. These propargylamines may prevent or rescue declining neurons
      induced by mitochondrial apoptotic cascade and may be applicable as
      "neuroprotective agents" in aging and age-related neurodegenerative disorders,
      such as Parkinson's and Alzheimer's diseases.

PMID- 11462788
TI  - Lack of protective effect by intermittent hypoxia on MPTP-induced neurotoxicity
      in mice.
AB  - In the study we report here, several lines of evidence support the preventive
      action of intermittent hypoxia against oxidative injuries in CNS. Our in vitro
      data showed that autooxidation and iron-induced lipid peroxidation were
      attenuated in cortical homogenates of intermittent hypoxia-treated animals.
      Furthermore, our preliminary study found that iron induced oxidative injuries
      were abolished in rat brain after intermittent hypoxic treatment (paper
      submitted). Several antioxidative defensive systems improve in response to
      intermittent hypoxia. Since attenuation of autooxidation and iron-induced lipid
      peroxidation were observed in cortical homogenates of intermittent hypoxia
      treated mice, the lack of prevention by intermittent hypoxia of MPTP-induced
      neurotoxicity may be due to the MPTP action that is not oxidative related.
      Together with our previous studies, in which several antioxidants were shown to
      successfully prevent oxidative injuries, our data here suggest that intermittent
      hypoxia may offer a potential treatment for preventing CNS degenerative diseases.

PMID- 11462789
TI  - Rescue of dying neurons by (R)-deprenyl in the MPTP-mouse model of Parkinson's
      disease does not include restoration of neostriatal dopamine.
AB  - Chronic (8- to 10-week) administration of the selective, potent, and irreversible
      monoamine oxidase B inhibitor (R)-deprenyl has been shown to increase the
      tyrosine hydroxylase immunoreactivity in the substantia nigra of mice that had
      been treated three days earlier with a neurotoxic dose of the parkinsonian
      inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This reported
      rescuing of lesioned nigrostriatal cell bodies by (R)-deprenyl prompted us to
      investigate if this (R)-deprenyl treatment also could restore neostriatal
      dopamine levels that are depleted by MPTP. The results of these experiments show
      that long term (8 or 10 weeks) treatment with (R)-deprenyl beginning three days
      post MPTP administration did not result in restoration of depleted neostriatal
      dopamine levels in C57BL/6 mice. We conclude that, although (R)-deprenyl may
      rescue MPTP-injured nigrostriatal neurons, it does not lead to functional
      recovery of these neurons as measured by the restoration of neostriatal dopamine
      levels.

PMID- 11462790
TI  - Gene therapy for treatment of cerebral ischemia using defective herpes simplex
      viral vectors.
AB  - Significant advances have been made over the past few years concerning the
      cellular and molecular events underlying neuron death. Recently, it is becoming
      increasingly clear that some of genes induced during cerebral ischemia may
      actually serve to rescue the cell from death. However, the injured cell may not
      be capable of expressing protein at high enough levels to be protective. One of
      the most exciting arenas of such interventions is the use of viral vectors to
      deliver potentially neuroprotective genes at high levels. Neurotropic herpes
      simplex viral (HSV) strains are an obvious choice for gene therapy to the brain,
      and we have used bipromoter vectors that are capable of transferring various
      genes to neurons. Using this system in experimental models of stroke, cardiac
      arrest, and excitotoxicity, we have found that it is possible to enhance neuron
      survival against such cerebral insults by overexpressing genes that target
      various facets of injury. These include energy restoration by the glucose
      transporter (GLUT-1), buffering calcium excess by calbindin, preventing protein
      malfolding or aggregation by stress proteins and inhibiting apoptotic death by
      BCL-2. We show that in some cases, gene therapy is also effective after the onset
      of injury, and also address whether successful gene therapy necessarily spares
      function. Although gene therapy is limited to the few hundred cells the vector is
      capable of transfecting, we consider the possibility of such gene therapy
      becoming relevant to clinical neurology in the future.

PMID- 11462791
TI  - Effect of L-carnitine pretreatment on 3-nitropropionic acid-induced inhibition of
      rat brain succinate dehydrogenase activity.
AB  - L-Carnitine (LC) plays an important regulatory role in the mitochondrial
      transport of long chain free fatty acids (FFA). 3-Nitropropionic acid (3-NPA) is
      known to induce cellular energy deficit and oxidative stress-related
      neurotoxicity via an irreversible inhibition of mitochondrial succinate
      dehydrogenase (SDH). In the present study, activity of SDH was measured in order
      to evaluate neuroprotective effects of LC against the 3-NPA-induced
      neurotoxicity. Male, CD Sprague-Dawley rats, three months old, were injected with
      either 50 or 100 mg/kg of LC, i.p., 30 min prior to 3-NPA (30 mg/kg, s.c.) or
      with 3-NPA alone. The activity of brain SDH was quantified spectrophotometrically
      in caudate nucleus (CN), frontal cortex (FC), and hippocampus (HIP) 60 min after
      the 3-NPA injection. The SDH activity in the animals treated with 3-NPA alone was
      38% (CN), 50% (FC), and 36% (HIP) that of saline controls. Pretreatment with LC
      prior to 3-NPA injection attenuated decreases of SDH activity by approximately 15
      and 29% (LC low and high dose, respectively). Despite the attenuation of SDH
      inhibition, the activity of SDH in these regions remained significantly lower in
      treated than in control rats (p < 0.05). It appears that the protective effect of
      LC against 3-NPA-induced oxidative stress cannot be explained by the direct
      action of LC to interfere with the SDH inhibition but are rather achieved by LC
      actions downstream of the SDH inhibition.

PMID- 11462792
TI  - Methamphetamine-induced dopaminergic neurotoxicity: role of peroxynitrite and
      neuroprotective role of antioxidants and peroxynitrite decomposition catalysts.
AB  - Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been
      known to be involved in a multitude of neurodegenerative disorders such as
      Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral
      sclerosis (ALS). Both ROS and RNS have very short half-lives, thereby making
      their identification very difficult as a specific cause of neurodegeneration.
      Recently, we have developed a high performance liquid
      chromatography/electrochemical detection (HPLC/EC) method to identify 3
      nitrotyrosine (3-NT), an in vitro and in vivo biomarker of peroxynitrite
      production, in cell cultures and brain to evaluate if an agent-driven
      neurotoxicity is produced by the generation of peroxynitrite. We show that a
      single or multiple injections of methamphetamine (METH) produced a significant
      increase in the formation of 3-NT in the striatum. This formation of 3-NT
      correlated with the striatal dopamine depletion caused by METH administration. We
      also show that PC12 cells treated with METH has significantly increased formation
      of 3-NT and dopamine depletion. Furthermore, we report that pretreatment with
      antioxidants such as selenium and melatonin can completely protect against the
      formation of 3-NT and depletion of striatal dopamine. We also report that
      pretreatment with peroxynitrite decomposition catalysts such as 5, 10,15,20
      tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and 5, 10, 15, 20
      tetrakis (2,4,6-trimethyl-3,5-sulfonatophenyl) porphinato iron III (FETPPS)
      significantly protect against METH-induced 3-NT formation and striatal dopamine
      depletion. We used two different approaches, pharmacological manipulation and
      transgenic animal models, in order to further investigate the role of
      peroxynitrite. We show that a selective neuronal nitric oxide synthase (nNOS)
      inhibitor, 7-nitroindazole (7-NI), significantly protect against the formation of
      3-NT as well as striatal dopamine depletion. Similar results were observed with
      nNOS knockout and copper zinc superoxide dismutase (CuZnSOD)-overexpressed
      transgenic mice models. Finally, using the protein data bank crystal structure of
      tyrosine hydroxylase, we postulate the possible nitration of specific tyrosine
      moiety in the enzyme that can be responsible for dopaminergic neurotoxicity.
      Together, these data clearly support the hypothesis that the reactive nitrogen
      species, peroxynitrite, plays a major role in METH-induced dopaminergic
      neurotoxicity and that selective antioxidants and peroxynitrite decomposition
      catalysts can protect against METH-induced neurotoxicity. These antioxidants and
      decomposition catalysts may have therapeutic potential in the treatment of
      psychostimulant addictions.

PMID- 11462793
TI  - Biomarkers of 3-nitropropionic acid (3-NPA)-induced mitochondrial dysfunction as
      indicators of neuroprotection.
AB  - In humans or animals, symptoms of mitochondrial energy dysfunction may be
      produced by mutations or inborn errors of the necessary enzymes, as well as by
      enzyme inhibitors or uncouplers of the oxidative phosphorylation process. 3
      Nitropropionic acid (3-NPA) is a toxin that is sometimes produced on moldy crops
      (sugarcane, peanuts, etc.) in amounts sufficient to cause severe neuromuscular
      disorders when consumed by humans. In vitro, 3-NPA irreversibly inactivates SDH,
      a Complex II respiratory enzyme important for mitochondrial energy production. We
      have been studying biomarkers of 3-NPA exposure in the expectation that such
      markers may be useful in the screening process to identify neuroprotective agents
      against neurotoxicity produced by mitochondrial energy dysfunction. Animals were
      sacrificed at various times after 3-NPA exposure for histochemical visualization
      of SDH activity and measurement of immediate postmortem rectal temperature. 3-NPA
      treated rats experienced progressive hypothermia that reached a loss of 3 degrees
      C or more in core body temperature by three hours after dosing. The optical
      density of the SDH stain in brain was reduced, following a similar time course,
      most prominently in the cerebellum and least sharply in the thalamus. Some rats
      were given injections of L-carnitine (an enhancer of fatty acid transport) either
      alone, or as a pretreatment prior to a dose of 3-NPA. Although L-carnitine
      deficiency by itself can produce mitochondrial dysfunction, pretreatment with L
      carnitine was of limited efficacy at overcoming the effects of 3-NPA on either
      body temperature or quantitative SDH histochemistry. Body temperature and SDH
      histochemistry may be useful biomarkers for evaluating the efficacy of
      neuroprotective agents against lower doses of 3-NPA, against other
      pharmacological models of mitochondrial dysfunction, or even against genetic
      mitochondrial diseases.

PMID- 11462795
TI  - Antiviral medications improve cerebrovascular perfusion in HIV+ non-drug users
      and HIV+ cocaine abusers.
AB  - Antiviral medications have been useful in delaying the time course of HIV
      infection. Antiviral medications have also been reported to delay or reduce
      symptoms associated with AIDS related dementia and to improve cortical perfusion.
      The mechanism for this improvement is unclear. Thus, this report studies the
      effects of antiviral medications on cerebral blood flow velocity in HIV+ cocaine
      abusers, HIV+ control individuals and appropriate control individuals. Thirty-two
      unmedicated HIV+ individuals (28 cocaine abusers and 4 control individuals), 22
      HIV+ individuals using antiviral medications (16 cocaine abusers and 6 HIV+
      control individuals), 47 HIV- cocaine abusers, and 27 control HIV- subjects were
      studied. Blood flow velocities were determined for the anterior and middle
      cerebral arteries using transcranial Doppler sonography. HIV+ individuals on
      antiviral medications had lower pulsatility values, suggesting decreased
      resistance in the cerebral blood vessels, in comparison to HIV+ individuals not
      taking antiviral medications. HIV+ cocaine abusers and HIV+ control individuals
      using antiviral medications had pulsatility values similar to HIV- control
      subjects. Antiviral medications appear to reduce these cerebrovascular perfusion
      deficits in HIV+ individuals. The antiviral medications appear to have a direct
      neuroprotective effect in addition to their antiviral effects. The
      neuroprotective role of antiviral medications requires further investigation.

PMID- 11462796
TI  - Marijuana abusers are at increased risk for stroke. Preliminary evidence from
      cerebrovascular perfusion data.
AB  - We have recorded blood flow velocity in the anterior and middle cerebral arteries
      by transcranial Doppler sonography in abstinent marijuana abusers (n = 16) and
      control subjects (n = 19) to assess the effects of prolonged marijuana use of the
      cerebrovascular system. The pulsatility index, a measure of cerebrovascular
      resistance, and systolic velocity were significantly (p < 0.005) increased in
      marijuana abusers compared to the control subjects. These findings suggest that
      cerebral perfusion observed in 18-30 year old marijuana abusers is comparable to
      that of normal 60 year-olds. Thus, chronic abuse of marijuana might be a risk
      factor for stroke.

PMID- 11462797
TI  - Delayed multidose treatment with nicotinamide extends the degree and duration of
      neuroprotection by reducing infarction and improving behavioral scores up to two
      weeks following transient focal cerebral ischemia in Wistar rats.
AB  - A single, delayed dose of nicotinamide (NAm) was shown to be protective against
      focal cerebral ischemia in rats, but the protection was limited to three to seven
      days following stroke. The investigation reported here was conducted to examine
      if the use of multiple doses of NAm, administered after the onset of focal
      cerebral ischemia, would extend the duration of neuroprotection compared with a
      single dose treatment regimen. Male Wistar rats were subjected to transient focal
      cerebral ischemia by occluding the right middle cerebral artery (MCAo) for two
      hours. Following MCAo, motor and sensory behavioral tests were performed daily
      and the cerebral infarct volumes were measured at two weeks after sacrifice. Each
      animal was placed into one of four groups that received either normal saline
      alone (Group S), one (Group A), two (Group B), or three (Group C) doses of NAm
      (500 mg/kg). Each animal, therefore, received three treatments over two weeks,
      with the first dose administered intravenously two hours after the onset of MCAo.
      Single and multiple doses of NAm reduced the infarction (p < 0.01) and improved
      (p < 0.05) the neurologic sensory and motor behavior when compared with the
      saline-treated animals up to two weeks after stroke. Moreover, animals that
      received multiple doses of NAm recuperated full motor function not different from
      normal, preoperative motor behavior. Delayed treatment with NAm given as multiple
      doses, therefore, further enhances the extent and duration of neuroprotection by
      significantly reducing cerebral infarct volumes, improving neurologic behavioral
      scores, and confers a complete motor recovery up to two weeks from the onset of
      focal cerebral ischemia in Wistar rats.

PMID- 11462798
TI  - Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer.
AB  - Dimebon, launched earlier in Russia as an antihistamine drug, was evaluated as a
      representative of a new generation of anti-Alzheimer's drugs that have two
      beneficial actions: (1) to alleviate symptoms, and (2) to prevent progression of
      the disease. The drug demonstrated cognition and memory-enhancing properties in
      the active avoidance test in rats treated with the neurotoxin AF64A, which
      selectively destroys cholinergic neurons. Dimebon protected neurons in the
      cerebellum cell culture against the neurotoxic action of beta-amyloid fragment (A
      beta 25-35, EC50 = 25 microM). In vitro, Dimebon displayed Ca(2+)-blocking
      properties (IC50 = 57 microM, on isolated rat ileum intestine) and pronounced
      anticholinesterase activity (IC50 = 7.9 microM and 42 microM for butyrylcholine
      esterase and acetylcholine esterase, respectively). It also exhibited strong anti
      NMDA activity in the prevention of NMDA-induced seizures in mice (EC50 = 42 +/- 6
      mg/kg i.p.). A beneficial effect of Dimebon in the therapy of Alzheimer's disease
      was demonstrated in a pilot clinical trial performed in the Moscow Center of
      Gerontology. Fourteen patients who participated in the trial were evaluated for
      their state of personality and for the severity of the disease. The evaluation
      included orientation (space, place, time, and patient personality), memory for
      the past and present, life in present, speech, irritability, and so forth. During
      and after the eight-week therapy with Dimebon, cognitive and self-service
      functions of patients improved significantly, and psychopathic symptoms, anxiety,
      depression, tearfulness, and headache were substantially diminished. The results
      of these studies suggest Dimebon as a new candidate for the therapy of
      Alzheimer's-like disorders.

PMID- 11462799
TI  - Cell death in spinal cord injury (SCI) requires de novo protein synthesis.
      Calpain inhibitor E-64-d provides neuroprotection in SCI lesion and penumbra.
AB  - Degradation of cytoskeletal proteins by calpain, a Ca(2+)-dependent cysteine
      protease, may promote neuronal apoptosis in the lesion and surrounding areas
      following spinal cord injury (SCI). Clinically relevant moderate (40 g-cm force)
      SCI in rats was induced at T12 by a standardized weight-drop method.
      Internucleosomal DNA fragmentation or apoptosis in the lesion was inhibited by 24
      h treatment of SCI rats with cycloheximide (1 mg/kg), indicating a requirement
      for de novo protein synthesis in this process. To prove an involvement of calpain
      activity in mediation of apoptosis in SCI, we treated SCI rats with a cell
      permeable calpain inhibitor E-64-d (1 mg/kg). Following 24-h treatment, a 5-cm
      long spinal cord section centered at the lesion was collected, and divided
      equally into five segments (1 cm each) to determine calpain activity, as shown by
      degradation of the 68-kD neurofilament protein (NFP), and apoptosis as indicated
      by internucleosomal DNA fragmentation. Neurodegeneration propagated from the site
      of injury to neighboring rostral and caudal regions. Both calpain activity and
      apoptosis were readily detectable in the lesion, and moderately so in neighboring
      areas of untreated SCI rats, whereas these were almost undetectable in E-64-d
      treated SCI rats, and absent in sham animals. Results indicate that apoptosis in
      the SCI lesion and penumbra is prominently associated with calpain activity and
      is inhibited by the calpain inhibitor E-64-d providing neuroprotective benefit.

PMID- 11462800
TI  - Neurogenesis and neuroprotection in the adult brain. A putative role for 5
      lipoxygenase?
AB  - 5-Lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are two enzymes that are
      critical for the synthesis of eicosanoids, the inflammatory metabolites of
      arachidonic acid. Both 5-LOX and COX-2 are expressed in the brain, including in
      CNS neurons. The physiologic role of these proteins in neuronal functioning is
      not clear. In non-neuronal tissues these two enzymes often assume similar roles:
      in addition to their function in inflammation, 5-LOX and COX-2 appear to be
      associated with cell proliferation, that is, with tumor growth. High 5-LOX
      expression has been noticed in the proliferating brain or pancreatic tumor cells;
      reduction in tumor cell proliferation and/or destruction of tumor cells was
      achieved with 5-LOX inhibitors. Proliferation of immature neurons/neuroblasts is
      an important component of mitotic neurogenesis. We investigated the role of 5-LOX
      in proliferation using cultures of human neuronal precursor cells, NT2. We found
      that these cells express 5-LOX mRNA and we used 3H-thymidine incorporation as a
      measure of cell proliferation; this was reduced by treating the cultures with 5
      LOX inhibitor AA-861. We propose that the 5-LOX pathway plays a crucial role in
      mitotic neurogenesis. Additional studies should explore whether 5-LOX may
      participate in neurogenesis related pathologies and whether it should be
      considered a target for procedures aimed at altering neurogenesis for therapeutic
      purposes.

PMID- 11462801
TI  - The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives
      exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo.
AB  - The antiapoptotic and neuroprotective activity of irreversible monoamine oxidase
      (MAO) B inhibitor, rasagiline [R(+)-N-propargyl-1-aminioindan], its S-isomer
      (TVP1022) and TV 3219, a novel anti-Alzheimer cholinesterase-MAO inhibitor drug
      derived from rasagiline were examined in PC12 cells cultures and in vivo. We
      found that these drugs have potent antiapoptotic and neuroprotective activities
      in response to serum and NGF withdrawal in partially neuronally differentiated
      PC12 cells and prevent the fall in mitochondrial membrane potential, the first
      step in cell death. Closed head injury studies in mice have shown that both
      rasagiline and TVP1022 are neuroprotective. All these compounds possess a
      propargyl moiety, which normally is responsible for irreversible inactivation of
      MAO, as is seen with rasagiline. However, neither TVP1022 nor TV3219 are MAO
      inhibitors, both share the antiapoptotic and neuroprotective actions of
      rasagiline, indicating that MAO inhibition is not a prerequisite for
      neuroprotection and that the propargyl moiety exhibits intrinsic neuroprotective
      pharmacological activity that requires identification.

PMID- 11462804
TI  - Modulation of cyclooxygenase-2 and brain reactive astrogliosis by purinergic P2
      receptors.
AB  - Astroglial cells respond to trauma and ischemia with reactive gliosis, a reaction
      characterized by increased astrocytic proliferation and hypertrophy. Although
      beneficial to a certain extent, excessive gliosis may be detrimental,
      contributing to neuronal death in neurodegenerative diseases. We have tested the
      hypothesis that ATP may act as a trigger of reactive gliosis in an in vitro model
      (rat brain primary astrocytes) where reactive astrogliosis can be quantified as
      elongation of astrocytic processes. Challenge of cells with the ATP analog
      alpha,beta methyleneATP (alpha,beta meATP) resulted in concentration dependent
      elongation of astrocytic processes, an effect that was fully counteracted by the
      non-selective ATP/P2 receptor antagonists suramin and pyridoxalphosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS). Signalling studies revealed that
      alpha,beta meATP-induced gliosis is mediated by a novel G-protein-coupled
      receptor (a P2Y receptor) coupled to an early release of arachidonic acid.
      Challenge of cells with alpha,beta meATP also resulted in an increase of
      inducible cyclooxygenase-2 (COX-2), the activity of which has been reported to be
      pathologically increased in a variety of neurodegenerative diseases characterized
      by inflammation and astrocytic activation. Induction of COX-2 by alpha,beta meATP
      was causally related to reactive astrogliosis, since the selective COX-2
      inhibitor NS-398 prevented both the purine-induced elongation of astrocytic
      processes and the associated COX-2 increase. Preliminary data on the putative
      receptor-to-nucleus pathways responsible for purine-induced gliosis suggest that
      induction of the COX-2 gene may occur through the protein kinase C/mitogen
      activated protein kinase system, and may involve the formation of activated AP-1
      transcription complexes. We speculate that antagonists selective at this novel
      P2Y receptor subtype may represent a novel class of neuroprotective agents able
      to slow down neurodegeneration by counteracting the inflammatory events
      contributing to neuronal cell death.

PMID- 11462805
TI  - The A3 adenosine receptor induces cytoskeleton rearrangement in human astrocytoma
      cells via a specific action on Rho proteins.
AB  - In previous studies, we have demonstrated that exposure of astroglial cells to A3
      adenosine receptor agonists results in dual actions on cell survival, with
      "trophic" and antiapoptotic effects at nanomolar concentrations and induction of
      cell death at micromolar agonist concentrations. The protective actions of A3
      agonists have been associated with a reinforcement of the actin cytoskeleton,
      which likely results in increased resistance of cells to cytotoxic stimuli. The
      molecular mechanisms at the basis of this effect and the signalling pathway(s)
      linking the A3 receptor to the actin cytoskeleton have never been elucidated.
      Based on previous literature data suggesting that the actin cytoskeleton is
      controlled by small GTP-binding proteins of the Rho family, in the study reported
      here we investigated the involvement of these proteins in the effects induced by
      A3 agonists on human astrocytoma ADF cells. The presence of the A3 adenosine
      receptor in these cells has been confirmed by immunoblotting analysis. As
      expected, exposure of human astrocytoma ADF cells to nanomolar concentrations of
      the selective A3 agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N
      methyluronamide (CI-IB-MECA) resulted in formation of thick actin positive stress
      fibers. Preexposure of cells to the C3B toxin that inactivates Rho-proteins
      completely prevented the actin changes induced by CI-IB-MECA. Exposure to the A3
      agonist also resulted in significant reduction of Rho-GDI, an inhibitory protein
      known to maintain Rho proteins in their inactive state, suggesting a potentiation
      of Rho-mediated effects. This effect was fully counteracted by the concomitant
      exposure to the selective A3 receptor antagonist MRS1191. These results suggest
      that the reinforcement of the actin cytoskeleton induced by A3 receptor agonists
      is mediated by an interference with the activation/inactivation cycle of Rho
      proteins, which may, therefore, represent a biological target for the
      identification of novel neuroprotective strategies.

PMID- 11462806
TI  - Adenosine extracellular brain concentrations and role of A2A receptors in
      ischemia.
AB  - Various experimental approaches have been used to determine the concentration of
      adenosine in extracellular brain fluid. The cortical cup technique or the
      microdialysis technique, when adenosine concentrations are evaluated 24 hours
      after implantation of the microdialysis probe, are able to measure adenosine in
      the nM range under normoxic conditions and in the microM range under ischemia. In
      vitro estimation of adenosine show that it can reach 30 microM at the receptor
      level during ischemia, a concentration able to stimulate all adenosine receptor
      subtypes so far identified. Although the protective role of A1 receptors in
      ischemia seems consistent, the protective role of A2A receptors appears to be
      controversial. Both A2A agonists and antagonists have been shown to be
      neuroprotective in various in vivo ischemia models. Although A2A agonists may be
      protective, mainly through peripherally mediated effects, A2A antagonists may be
      protective through local brain mediated effects. It is possible that A2A
      receptors are tonically activated following a prolonged increase of adenosine
      concentration, such as occurs during ischemia. A2A receptor activation
      desensitizes A1 receptors and reduces A1 mediated effects. Under these conditions
      A2A receptor antagonists may be protective by potentiating all the
      neuroprotective A1 mediated effects, including decreased neurotoxicity due to
      reduced ischemia induced glutamate outflow.

PMID- 11462807
TI  - Right thing at a wrong time? Adenosine A3 receptors and cerebroprotection in
      stroke.
AB  - The involvement of adenosine A3 receptors in normal and pathologic functions of
      the brain remains to be defined. Previous studies have shown that chronic
      preischemic administration of the agonist [N6-(3-iodobenzyl)-5'-N
      methylcarboxoamidoadenosine or IB-MECA) results in a significant protection of
      neurons in selectively vulnerable brain regions and in an equally significant
      reduction of the subsequent mortality. Acute administration of the drug, on the
      other hand, resulted in a pronounced worsening of these parameters. We now report
      that the effect of administration of IB-MECA depends on the timing of treatment
      with respect to the onset of the focal insult, and provide the first data
      supporting speculation that treatment with adenosine A3 receptor agonists may
      decrease the infarct size following focal brain ischemia. Treatment with IB-MECA
      administered 20 min prior to transient middle cerebral ischemia (MCAOt = 30 min)
      resulted in a significant increase of the infarct size (p < 0.01), whereas
      administration 20 min after ischemia resulted in statistically significant
      decrease of the infarct volume. Postischemic treatment results in improved
      neuronal preservation, decreased intensity of reactive gliosis, and pronounced
      reduction of microglial infiltration. The data indicate that the effects of
      adenosine A3 receptor stimulation depend on the differential impact of these
      receptors on both neuronal and non-neuronal elements of the cerebral tissue, for
      example, astrocytes, microglia, and vasculature.

PMID- 11462809
TI  - Nuclear magnetic resonance relaxation in determination of residue-specific 15N
      chemical shift tensors in proteins in solution: protein dynamics, structure, and
      applications of transverse relaxation optimized spectroscopy.
AB  - We developed several approaches to direct determination of the 15N CSA from
      relaxation measurements in uniformly 15N-labeled proteins in solution. These
      methods are based on multiple-field measurements and could be extended to other
      nuclei in proteins and other molecules. Combined with the isotropic chemical
      shift measurements, this provides an experimental approach to full
      characterization of chemical shift tensors in proteins in their native milieu,
      which is likely to provide valuable information on the nature of chemical shifts
      and their relation to protein structure. Knowledge of 15N CSA is essential for an
      accurate characterization of protein dynamics from relaxation measurements.

PMID- 11462810
TI  - Dipolar couplings in macromolecular structure determination.

PMID- 11462811
TI  - Nuclear magnetic resonance methods for high molecular weight proteins: a study
      involving a complex of maltose binding protein and beta-cyclodextrin.

PMID- 11462812
TI  - Optimization of protein solubility and stability for protein nuclear magnetic
      resonance.

PMID- 11462813
TI  - Nuclear magnetic resonance methods for quantifying microsecond-to-millisecond
      motions in biological macromolecules.

PMID- 11462814
TI  - Characterizing protein-protein complexes and oligomers by nuclear magnetic
      resonance spectroscopy.

PMID- 11462815
TI  - Nuclear magnetic resonance methods for elucidation of structure and dynamics in
      disordered states.

PMID- 11462816
TI  - Micellar systems as solvents in peptide and protein structure determination.

PMID- 11462817
TI  - Nuclear magnetic resonance of membrane-associated peptides and proteins.

PMID- 11462818
TI  - Physiological conditions and practicality for protein nuclear magnetic resonance
      spectroscopy: experimental methodologies and theoretical background.

PMID- 11462819
TI  - Paramagnetic probes in metalloproteins.

PMID- 11462820
TI  - Protein-DNA interactions.

PMID- 11462821
TI  - Nuclear magnetic resonance methods to study structure and dynamics of RNA-protein
      complexes.

PMID- 11462822
TI  - Protein-protein interactions probed by nuclear magnetic resonance spectroscopy.

PMID- 11462823
TI  - Solid-state nuclear magnetic resonance techniques for structural studies of
      amyloid fibrils.

PMID- 11462824
TI  - Segmental isotopic labeling using expressed protein ligation.

PMID- 11462825
TI  - High-resolution nuclear magnetic resonance of encapsulated proteins dissolved in
      low viscosity fluids.

PMID- 11462826
TI  - Automated assignment of ambiguous nuclear overhauser effects with ARIA.

PMID- 11462827
TI  - Automatic determination of protein backbone resonance assignments from triple
      resonance nuclear magnetic resonance data.

PMID- 11462828
TI  - Construction of microsatellite-based, high-resolution genetic maps in the mouse.

PMID- 11462829
TI  - Mapping of genomic clones by fluorescence in situ hybridization.

PMID- 11462830
TI  - Genetic analysis of complex traits.

PMID- 11462831
TI  - Map integration. From a genetic map to a physical gene map and ultimately to the
      sequence map.

PMID- 11462832
TI  - Construction of full-length-enriched cDNA libraries. The oligo-capping method.

PMID- 11462833
TI  - Construction of transcript maps by somatic cell/radiation hybrid mapping. The
      human gene map.

PMID- 11462834
TI  - Preparation and screening of high-density cDNA arrays with genomic clones.

PMID- 11462835
TI  - Direct selection of cDNAs by genomic clones.

PMID- 11462836
TI  - Exon trapping. Application of a large-insert multiple-exon-trapping system.

PMID- 11462837
TI  - Sequencing bacterial artificial chromosomes.

PMID- 11462838
TI  - Finding genes in genomic nucleotide sequences by using bioinformatics.

PMID- 11462839
TI  - Gene identification using the pufferfish, Fugu rubripes, by sequence scanning.

PMID- 11462840
TI  - Isolation of differentially expressed genes through subtractive suppression
      hybridization.

PMID- 11462841
TI  - Isolation of differentially expressed genes by representational difference
      analysis.

PMID- 11462842
TI  - Sequence-based detection of single nucleotide polymorphisms.

PMID- 11462843
TI  - Expression profiling and isolation of differentially expressed genes by indexing
      based differential display.

PMID- 11462844
TI  - Expression profiling by systematic high-throughput in situ hybridization to whole
      mount embryos.

PMID- 11462845
TI  - Expression monitoring using cDNA microarrays. A general protocol.

PMID- 11462846
TI  - Prediction of protein structure and function by using bioinformatics.

PMID- 11462847
TI  - Genomic mismatch scanning for the mapping of genetic traits.

PMID- 11462848
TI  - Identification of novel genes by gene trap mutagenesis.

PMID- 11462849
TI  - Determination of gene function by homologous recombination using embryonic stem
      cells and knockout mice.

PMID- 11462850
TI  - Genomic analysis utilizing the yeast two-hybrid system.

PMID- 11462851
TI  - Methods for adeno-associated virus-mediated gene transfer into muscle.

PMID- 11462852
TI  - Detection of chromosomal abnormalities by comparative genomic hybridization.

PMID- 11462853
TI  - Retroviral-mediated gene transduction.

PMID- 11462854
TI  - Gene therapy approaches to sensitization of human prostate carcinoma to cisplatin
      by adenoviral expression of p53 and by antisense jun kinase oligonucleotide
      methods.

PMID- 11462855
TI  - Ribozyme gene therapy.

PMID- 11462856
TI  - Construction of a bacterial artificial chromosome library.

PMID- 11462857
TI  - Contiguation of bacterial clones.

PMID- 11462858
TI  - Variations of pelvic anteversion in the lying and standing positions: analysis of
      24 control subjects and implications for CT measurement of position of a
      prosthetic cup.
AB  - The position of the acetabular implant plays a dominant role in the displacement
      of a total hip prosthesis. CT allows precise measurement of the position of the
      cup, but the influence of pelvic rotation on this measurement is unknown. The aim
      of this study was to determine, in a group of healthy subjects, whether a pelvic
      equilibrium exists specific to each individual, and whether this is constant over
      time on the one hand and between the standing and lying positions on the other.
      The study concerned 15 men and 9 women with a mean age of 31 years. Each subject
      had strictly lateral radiographs of the pelvis, lying and standing, repeated at
      two different times. Pelvic version was measured in these radiographs. Each
      individual had a pelvic position constant over time, both in the lying and
      standing positions. However, there were important variations of the position of
      the pelvis during passage from the lying to the standing position: 22 patients
      had retroversion of the pelvis by a mean of 7 degrees (2-18 degrees) and 2 others
      had an anteversion of 3 degrees. These major variations of the pelvic position
      between the standing and lying positions explain why CT studies made in the lying
      position do not allow for the anteversion of the cup in the standing position,
      which is close to the dynamic situation during which displacement may occur.
      Thus, an excessive anteversion of the cup may be masked when the scan is made in
      the lying position, since in this position the anteversion of the pelvis leads to
      retroversion of the cup. The error may reach 20 degrees, so that we recommend
      that CT measurements made without allowing for the position of the pelvis should
      be interpreted with caution.

PMID- 11462859
TI  - The precision of ultrasound imaging and its relevance for carpal tunnel syndrome.
AB  - The carpal tunnel syndrome (CTS) is the most common peripheral entrapment
      neuropathy in human. The diagnosis is based on symptoms and on physical
      examination and is supported by nerve conduction tests. The aim of this study was
      to evaluate the precision and the valence of ultrasound (US) for CTS. An anatomic
      study was performed on 40 wrists of 20 unfixed human cadavers. The carpal tunnel
      and its important structures and contents were imaged and measured by ultrasound
      (7.5-MHz high resolution probe). The dorsopalmar diameter (DPD), the radioulnar
      diameter (RUD), the perimeter (P) and the cross-sectional area (A) were
      determined for the carpal canal and for the median nerve. These US images and
      measurements were directly compared with anatomic cross-sections gained from the
      same wrists at the same level. Our results showed that ultrasound is a very
      precise method to display the anatomy of the carpal tunnel and of the median
      nerve and thus the conditions of the median nerve. Significant differences could
      not be detected for each of these parameters either for the carpal tunnel or the
      median nerve. (Ultrasound: cross-sectional area of carpal tunnel: 162.4 +/- 29.3
      mm2 and of the median nerve: 9.2 +/- 2.4 mm2; anatomy: cross-sectional area of
      carpal tunnel: 168.4 +/- 31.2 mm2 and of median nerve: 9.4 +/- 2.2 mm2).

PMID- 11462860
TI  - High bifurcation of common carotid artery, anomalous origin of ascending
      pharyngeal artery and anomalous branching pattern of external carotid artery.
AB  - We present a rare case of combined high bifurcation of the common carotid artery,
      anomalous origin of the ascending pharyngeal artery and unusual branching pattern
      of the external carotid artery. The right common carotid artery bifurcated at the
      level between the second and the third cervical vertebrae, giving rise to the
      ascending pharyngeal artery just below the bifurcation. The right external
      carotid artery branched directly at its origin into the superior thyroid, lingual
      and occipital arteries and the distal part of the external carotid artery. The
      latter gave rise to the right facial artery and finally bifurcated into the
      maxillary and superficial temporal arteries. The right posterior auricular artery
      arose from the right occipital artery. The finding was unilateral and other
      vascular anomalies were not observed. The embryogenesis of such a combination of
      anomalies is not clear, but the anatomic consequences may have important clinical
      implications.

PMID- 11462861
TI  - Bilateral origin of the internal thoracic artery from the third part of the
      subclavian artery: a case report.
AB  - The routine use of the internal thoracic artery (ITA) as a conduit in coronary
      artery bypass grafting surgery has highlighted the need to appreciate this
      vessel's anatomic variations. The usual origin of this vessel is from the first
      part of the subclavian artery, occasionally from the second and rarely from the
      third. Henriques-Pino and Prates described a unilateral origin from the third
      part on the left and Vorster et al on the right. Our cadaveric case report
      presents an unusual bilateral origin of the ITA arising from the third part of
      the subclavian artery in a 25-year-old Black South African female. The ITA arose
      from the ventral aspect, 7.3 cm on the right side and 8.5 cm on the left side
      from the origin of the subclavian artery, and inclined acutely inferiorly and
      medially, anterior to the distal attachment of the scalenus anterior m., followed
      the inner border of the first rib for a short distance and, thereafter, continued
      its usual course in the thorax. This appears to be the first case report
      presenting a bilateral origin of the ITA from the third part of the subclavian
      artery.

PMID- 11462862
TI  - Unilateral absence of the thoracic part of the trapezius muscle.
AB  - The absence of some muscles, such as pectoralis major, serratus anterior and
      quadratus femoris have been described, however the absence of trapezius, either
      in isolation or in association with other structures, is not often observed. In
      this case study, we present a case of partial absence of the left trapezius
      muscle in an adult black male cadaver, which had a large aponeurosis replacing
      the ascending fibres and some of the transverse fibres of the muscle.
      Histological analysis showed the presence of a few muscle fibres in the
      aponeurosis. From a functional viewpoint, it is possible that this individual
      would have had difficulty in moving his shoulder, especially during flexion,
      abduction and circumduction of the arm.

PMID- 11462863
TI  - Thyrolingual trunk arising from the common carotid artery: a case report.
AB  - During a cadaver dissection in the anatomy department of the University of Liege,
      Belgium, an anatomic variation of the superior thyroid and lingual arteries was
      observed on the right side in a 68-year-old woman. Both arteries arose from a
      common trunk located 30 mm beneath the carotid bifurcation. After a 5.2 mm
      course, the thyrolingual trunk divided into superior thyroid and lingual arteries
      which followed an unusual course towards their respective organs. Knowledge of
      this anomaly is important for those who are involved with neck surgery and
      anatomy.

PMID- 11462864
TI  - Bilateral case of superficial ulnar artery originating from axillary artery.
AB  - During the dissection of an 86-year-old male human cadaver, superficial ulnar
      arteries were found in both upper limbs. These arteries branched from the
      axillary arteries. In the left arm, the artery crossed ventral to the medial root
      of the median nerve before running towards the medial part of the arm. The
      persistence of the median artery was noted. In the right arm, the ulnar artery
      had a common origin with the subscapular artery. It crossed anterior to the
      lateral root of the median nerve and then, in the arm, ran alongside the
      anterolateral aspect of the median nerve, near the biceps brachii muscle, which
      was supplied by this superficial ulnar artery. Then the artery crossed the median
      nerve and the brachial artery. The embryology, incidence and clinical relevance
      of this anatomical variation are discussed. So this was a rare case where the
      ulnar arteries originated from the axillary artery on both sides, but then
      followed different courses in the arm and, on the right side, the superficial
      ulnar artery partly supplied the biceps brachii muscle.

PMID- 11462865
TI  - Anatomical basis of latissimus dorsi and teres major transfers in rotator cuff
      tear surgery with particular reference to the neurovascular pedicles.
AB  - Musculotendinous transfers (MTT) of latissimus dorsi (LD) and teres major (TM),
      either in isolation or combination, have recently been advocated to treat
      irreparable rotator cuff tears. The purpose of this study was to (1) review the
      anatomy of the LD and TM neurovascular pedicles, and (2) undertake experimental
      MTT to humeral insertions of either supraspinatus or infraspinatus to evaluate
      tension on their nutrient arteries in six positions of the arm. Twenty-six
      shoulders were studied, 22 of which had previously been injected with red latex.
      Gross dissection, using 4.3 x magnification when necessary, was followed by one
      MTT for each shoulder (11 LD, 6 TM, 9 combined). The anatomy of the LD and TM
      neurovascular pedicles was consistent with classic descriptions in 85% of cases;
      "medialisation" of the thoracodorsal artery was observed in 4 specimens. Tension
      on the teres major artery was not observed in 15 isolated or combined MTTs, while
      tension on the thoracodorsal artery in at least one arm position was observed in
      60% of 20 isolated or combined MTTs. Three factors were found to be associated
      with tension: medialisation of the thoracodorsal artery, fixation onto the
      supraspinatus insertion, and 90 degrees abduction combined with internal
      rotation. The results suggest that tension on the thoracodorsal artery is
      possible under certain circumstances when an isolated LD or combined MTT is
      performed to treat irreparable rotator cuff tear.

PMID- 11462866
TI  - Posterior approach for simultaneous access to the popliteal and anterior tibial
      arteries: applications to distal arterial bypass.
AB  - Arterial surgery to salvage the lower limb tends to make use of the great
      saphenous vein, harvested with the subject in the supine position. If this is not
      possible the small saphenous vein is used, harvested with the subject in the
      prone position, however this requires a perioperative modification of the
      procedure. A bypass between the popliteal and anterior tibial arteries can be
      performed using either a lateral or a medial and lateral approach with the
      patient supine. In the event of trophic disorders of the lateral compartment of
      the leg, these approaches are not applicable. In such cases we propose a single
      posterior approach. The single posterior approach was used on 10 lower limbs from
      5 cadavers in the prone position. Approach to the lower part of the popliteal
      artery was undertaken posteriorly between the two heads of gastrocnemius. The
      small saphenous vein was entirely dissected 10 cm above the lateral malleolus,
      the Achilles tendon and short fibular vessels were retracted medially to expose
      the interossous fascia, which was divided over 10 cm. Medial rotation of the limb
      by 30 degrees exposed the anterior tibial artery. For 3 of the lower limbs an 8
      cm fibular resection was necessary, whereas on the remaining 7 medial rotation
      enabled excellent exposure of the anterior tibial artery. The single posterior
      approach to the anterior tibial artery can be applied in cases requiring distal
      bypass, using the small saphenous vein, between the inferior part of the
      popliteal artery and the anterior tibial artery.

PMID- 11462867
TI  - Vertebral pedicle anatomy in relation to pedicle screw fixation: a cadaver study.
AB  - New techniques to stabilize and correct the thoracic and lumbar spine have been
      developed in recent years. In view of the wide variety and complexity of fixation
      devices, the optimum configuration of spinal instrumentation systems needs to be
      defined. Linear and angular measurements of both vertebral pedicles were made in
      ten complete thoracic and lumbar cadaveric spines using callipers and a
      goniometer. The vertical interpedicular distance gradually increased along the
      spine up to L5. The transverse interpedicular distance was larger at both ends of
      the spine. Pedicular height gradually increased from T1 to L5, plateauing between
      T3 and T9, being widest at the thoracolumbar junction. Pedicular width was
      greatest at the three junctional regions of the spine. The sagittal pedicular
      angle decreased along the length of the spine to zero at L5. The transverse
      pedicular angle decreased from T1 to T12 and then increased to L5. Of the
      pedicular measurements only width limits the diameter of fixation screws. The
      vertical interpedicular distance determines the distance between the holes of
      plates, while the length of the transfixator is related to the transverse
      interpedicular distance. The pedicular angles enable triangulation of screws and
      determine the stability of the fixation.

PMID- 11462868
TI  - Significance of the auditory tube angle and mastoid size in chronic ear disease.
AB  - The aim of this study was to determine whether a relationship exists between
      mastoid size and auditory tube angle (ATA) and chronic ear disease. A
      radiological and clinical study was undertaken of the temporal bones of 36
      subjects. There were 24 patients with unilateral chronic otitis media (COM) and
      12 healthy controls (HC): the contralateral healthy ears of the COM patients were
      also used as control (CLHC). From each CT scan the distance between Henle spine
      and the sigmoid sinus (H-SS) and the ATA was assessed. The angle between a
      longitudinal line bisecting the transverse length of the external auditory canal
      and the longitudinal axis of the AT was calculated. A direct correlation between
      H-SS and ATA, both in COM and HC (p < 0.01), was observed, but not in CLHC (p >
      0.05). There was no significant difference in the ATA results between COM and
      CLHC, or between COM and HC (p > 0.05), however there was a significant
      difference between CLHC and HC (p = 0.02). H-SS distances were not significantly
      different between COM and CLHC, or COM and HC, or CLHC and HC (p > 0.05). An
      association between ATA and mastoid size in both healthy and diseased ears was
      observed. The anatomical relationships of the AT, mastoid and middle ear, which
      form a functional unit, are not significantly important in chronic ear disease.

PMID- 11462870
TI  - No free lunch.

PMID- 11462869
TI  - The frontotemporal peripheral nerves. Topographic variations of the supraorbital,
      supratrochlear and auriculotemporal nerves and their possible clinical
      significance.
AB  - The peripheral topography of the supraorbital (SON) and supratrochlear (STN)
      nerves and the superficial temporal branch of the auriculotemporal nerve (ATN)
      was investigated in 10 cadavers. The aim was to define the optimal locations for
      anaesthetic nerve blocks, as well as to help surgeons prevent nerve injuries.
      Specific measurements on the nerve "exits" in relation to defined landmarks are
      presented. The variability of the supraorbital notches and peripheral branching
      of the dissected nerves suggests several methods for anaesthetic blocks in cases
      of surgical and clinical head pain. The optimum injection site for a selective
      SON block is 20-30 mm from the midline (range 15-33 mm); reinjection at 30-50 mm
      from the midline might complete inefficient nerve block. For selective SON block
      the distance between the main SON and STN branches (mean 15.3 mm) should also be
      considered. The ATN is best blocked at a point located at the level with and 10
      15 mm (range 8-20 mm) anterior to the upper origin of the helix. Separate exits
      for the medial and lateral SON branches were observed in eight of the 20 nerves
      examined. Twenty of the 28 exits were foraminae completed by bony or connective
      tissue. In many cases both the SON and STN ascended close to the associated
      artery: in six cases a tissue band covered the nerve and vessel at the orbital
      exit. Some of the observed structures associated with the nerve might be pain
      generators, however the present study does not provide any evidence for such a
      hypothesis.

PMID- 11462871
TI  - [Continuing education must be taken seriously! To be on "educational leave" is
      considered by many workplaces as an extra expenditure and not as an investment in
      human capital].

PMID- 11462872
TI  - [Continuing should be a part of the clinical reality. Courage is required to see
      both the strong and the weak sides of the professional situation].
AB  - Continuing professional development (CPD) is a joint responsibility of the
      individual physician and the employer. CPD should focus on identification and
      documentation of the learning needs of the individual, based on professional
      demands. Reflection, feedback and evaluation of the results are central elements
      of the process. Efficient learning demands active participation; modern
      information technology is now becoming more widely available.

PMID- 11462873
TI  - [Candid, not monitored children run less risk of becoming delinquent].
AB  - Monitoring (tracking and surveillance) of children's behavior is considered an
      essential parenting skill. Numerous studies show that well monitored youths are
      less involved in delinquency and other norm-breaking behaviors, and scholars
      conclude that parents should track their children more carefully. We have
      questioned that conclusion. We point out that monitoring measures typically
      assess parents' knowledge, but not its source, and parents could derive knowledge
      from their children's free disclosure of information as well as their own active
      surveillance efforts. In our study of 14-year-olds in central Sweden and their
      parents, parental knowledge came mainly from child disclosure, and child
      disclosure was the source of knowledge that was most closely linked to broad and
      narrow measures of delinquency (norm-breaking and police contact). Parents'
      control efforts were related to good adjustment only after the child's feelings
      of being controlled, which were linked to poor adjustment, were partialled-out.
      These results held for both children's and parents' reports, for both sexes, and
      independent of whether the children were exhibiting problem behavior or not. We
      conclude that tracking and surveillance is not the best prescription for parental
      behavior, and a new prescription must rest on an understanding of the factors
      that determine child disclosure. As adolescents spend increasing amounts of time
      away from home, parental trust should become important, but little is known about
      how trust develops. We propose that parental trust is based on knowledge,
      primarily. We have pitted three types of knowledge about the child against each
      other in the prediction of parental trust--knowledge of: feelings and concerns,
      past delinquency, and daily activities. Results showed that knowledge of daily
      activities was more important than knowledge of past delinquency. In further
      analyses, knowledge of daily activities that came from the child's spontaneous
      disclosure was most closely linked to parents' trust. These findings add support
      to our reinterpretation of parental "monitoring" as parental knowledge that
      mainly comes from spontaneous child disclosure. Additionally, the role of
      parental trust for dysfunctional family relations was examined, and it was found
      that the relations between the child's delinquency and family dysfunction were
      mediated by parental trust. Finally, even though there was substantial agreement
      between parents and children about parents' trust in the child, the individual's
      unique perspectives were important. Family dysfunction from the child's
      perspective was based on whether they believed that their parents trusted them,
      and parents' perceptions of family dysfunction were based on their trust in the
      child.

PMID- 11462874
TI  - [International consensus meeting on fatigue and the risk of traffic accidents.
      The significance of fatigue for transportation safety is underestimated].
AB  - Recently there has been a sizeable increase in research on fatigue and accidents
      in transportation. Therefore a meeting was convened last year to discuss
      prevalence, mechanisms and countermeasures, with the intention to produce an
      international consensus document. It was concluded that official statistics
      strongly underestimate prevalence, and that a reasonable estimate, based on
      research, lies between 10 and 20% for accidents on the road, in the air and at
      sea. The main causes are disturbed sleep and work at the circadian low, caused by
      night work, morning work, sleep/wake disorders (including sleep apnea) or social
      obstacles to sleep. Suggested countermeasures include information/education of
      the public and of transportation companies, as well as enforcement of existing
      work hour regulation. Additional countermeasures include strategic use of napping
      and caffeine, as well as implementation of rumble strips and--possibly-
      electronic devices for drowsiness detection.

PMID- 11462875
TI  - [Drowsiness--greater traffic hazard than alcohol. Causes, risks and treatment].
AB  - Stress and shortage of sleep may cause daytime somnolence and impaired vigilance
      at the wheel, especially among those suffering from sleep disturbances. According
      to the international consensus meeting in Stockholm in May of 2000 on "The sleepy
      driver and pilot--causes, risks and countermeasures", drowsy driving is an
      underestimated risk factor in official statistics, and as many as 15-30 percent
      of today's traffic accidents are related to drowsiness; thus it is an even
      greater risk factor than alcohol. Drowsy drivers suffer from inattention,
      impaired concentration and may even fall asleep at the wheel. Accidents during
      dozing result in three times as many fatalities as other accidents. There are a
      number of reasons for habitual drowsiness at the wheel aside from sleep
      deprivation, including rhonchopathy, shift work and jet lag, mental depression,
      insomnia, narcolepsy, endocrinological diseases, periodic limb movement disorder,
      medication, pain-disordered sleep, and heart disease. Among the most active
      drivers, i.e. middle aged men, obstructive sleep apnea syndrome (OSAS) has been
      found to be the most common reason for habitually drowsy driving. OSAS causes a 2
      3 fold increased risk of traffic accidents, and it impairs simulated driving.
      Palatoplasty as well as nasal CPAP have been shown to improve vigilance and
      driving performance to an extent that the increase in risk is eliminated. Drivers
      suffering from habitual drowsiness and micro-sleep attacks forcing them to take
      repeated rests are at special risk. Even if they are as dangerous as drivers with
      unlawful blood alcohol levels they cannot be caught in a police checkpoint.
      However they often seek medial advice, and properly treated they may often return
      safely to traffic. If not, there could be a need to report them to the
      authorities so as to limit or prohibit their driving.

PMID- 11462876
TI  - [Hereditary thyroid cancer can be cured by prophylactic surgery].
AB  - Multiple endocrine neoplasia type 2 (MEN 2) is a rare syndrome in which the
      consequences for the patient and family members are considerable. Mutation
      analysis of the RET proto-oncogene is crucial for decision-making regarding each
      patient. Today, carriers of MEN 2 mutations should be offered prophylactic
      thyroidectomy with the potential to eliminate the risk for potentially lethal
      medullary thyroid carcinoma (MTC). Here, we present the first Swedish experience
      of such operations performed mainly on the basis of genetic analysis. Twenty
      patients underwent total thyroidectomy at a mean age of 13.5 (6-43) years. In all
      cases, either manifest MTC (n = 11) or C-cell hyperplasia was found. So far, no
      patient has any sign of recurrence or developmental insufficiency at 1-5 years
      follow-up. As the medical and ethical problems in this group of patients are
      substantial, and as the operations are performed in otherwise healthy children,
      they should be treated at centers with adequate multidisciplinary expertise and
      competence.

PMID- 11462877
TI  - [Reduced cost-effectiveness of depression screening].

PMID- 11462878
TI  - [Snuff doesn't interfere with alcohol breath test].

PMID- 11462879
TI  - [Time for continuing education is in short supply for general practitioners-
      results from a questionnaire study].

PMID- 11462880
TI  - [Quality of health care. What is it and how can it be measured?].

PMID- 11462881
TI  - [When the "tiger" from Teneriffa crushed admiral Nelson's arm].

PMID- 11462882
TI  - [A vision of a new health care system: with a "health care check" can citizens
      make their own choices].

PMID- 11462883
TI  - [Whiplash injuries has an unambiguous organic basis].

PMID- 11462884
TI  - [Final reply on ADHD/DAMP: wrong statements will not become more truthful by
      repeating them].

PMID- 11462885
TI  - [Happy return of hypothermia as a therapeutic method in neonatal asphyxia].

PMID- 11462886
TI  - Spot urine 5-hydroxy indole acetic acid and acute appendicitis.
AB  - BACKGROUND/AIMS: Appendectomy for suspected appendicitis cases is a common
      procedure. Its clinical diagnosis needs to be supported by accurate confirmatory
      tests. No single paraclinical test with a high degree of sensitivity and
      specificity is available for its diagnosis. The appendix contains numerous
      serotonin-producing cells (enterochromaffin cells). In the inflammatory process
      and subsequent cell injury, serotonin is released and converted to 5-HIAA (5
      hydroxy indole acetic acid). We studied the elevation of 5-HIAA in the spot urine
      of acute appendicitis patients. METHODOLOGY: 5-HIAA was measured by high
      performance liquid chromatography in the spot urine samples of 40 healthy
      individuals and 166 patients who presented to emergency units of the university
      hospitals with acute abdominal pain. The results of the urine concentrations were
      compared to the histopathology reports of the removed appendices and the final
      diagnosis of other diseases. RESULTS: From 80 cases with a presumptive diagnosis
      of appendicitis, 73 were operated on and seven cases discharged after a few hours
      observation. Sixty-five out of 66 documented appendicitis patients showed a
      striking increase of urinary spot 5-HIAA with significant differences vs. all
      cases of healthy control individuals (P < 0.001). The 5-HIAA values of all of the
      negative appendectomy cases (n = 7) and all of the discharged cases after the
      observation period (n = 7) were within healthy control ranges. The mean value of
      the appendicitis group (42.76 +/- 2.26 mumol/L) was also significantly higher vs.
      all other acute abdomens which could mimic acute appendicitis (P < 0.05)
      excepting gastroenteritis patients. Considering 20 mumol/L as the cutoff value
      sensitivity, specificity, positive and negative predictive values of this test
      for discriminating appendicitis in clinically suspected patients were 98%, 100%,
      100% and 93%, respectively and in all acute abdomens were 98%, 71%, 69% and
      98.6%, respectively. The patients with gastroenteritis also showed elevation of 5
      HIAA (43.05 +/- 2.7 mumol/L) vs. other nonappendicitis groups (P < 0.05).
      CONCLUSIONS: We have concluded that measurement of 5-HIAA in spot urine is a
      highly reliable test supporting the clinical diagnosis of appendicitis and if it
      does not show an increase, appendicitis can be ruled out with a very high degree
      of confidence which helps to reduce unnecessary appendectomies. In clinically
      suspected appendicitis patients with diarrhea, an increase of 5-HIAA may not
      confirm the diagnosis.

PMID- 11462887
TI  - Evaluation of an office-based urine test for detecting Helicobacter pylori: a
      Prospective Pilot Study.
AB  - BACKGROUND/AIMS: To ascertain the reliability of a newly developed office-based
      urine test, the RAPIRUN test, used for detection of H. pylori infection.
      METHODOLOGY: Urine specimens from 142 consecutive patients undergoing
      gastroendoscopy (77 men, 65 women; mean 52.0 years) were tested with RAPIRUN at
      the same time. The total reaction time for the urine test is 20 min. None of the
      patients had received any H. pylori eradicating treatment. The H. pylori status
      was evaluated based on 5 different tests: culture, histology, biopsy urease test,
      13C-urea breath test, and the RAPIRUN test. A commercial office-based kit using
      an immunochromatographic technique was used to examine urine samples for H.
      pylori antibody. H. pylori status was defined as positive when the culture was
      positive or if 2 of the other 3 tests (histology, biopsy urease test, and 13C
      urea breath test were positive. RESULTS: Of 93 patients with H. pylori infection,
      88 were tested as positive by RAPIRUN (sensitivity 94.6%). Of 48 patients without
      infection, 43 were found to be negative by RAPIRUN (specificity 89.6%). One case
      with an invalid urine test was excluded. CONCLUSIONS: This urine test is a rapid,
      inexpensive, reliable and easy-to-use tool for the diagnosis of H. pylori
      infection in untreated patients. It can be used for mass screening of patients'
      H. pylori status, particularly in children, postgastrectomy patients,
      uncooperative patients, and patients undergoing bismuth or proton pump inhibitor
      treatment.

PMID- 11462888
TI  - Rapid diagnosis of choledocholithiasis using biochemical tests in patients
      undergoing laparoscopic cholecystectomy.
AB  - BACKGROUND/AIMS: The present study was designed to identify the biochemical tests
      which could detect the presence of common bile duct stones in patients with
      symptomatic gallstones, without other invasive investigations. The usefulness of
      biochemical tests may reduce the necessity of endoscopic retrograde
      cholangiopancreatography prior to laparoscopic cholecystectomy. METHODOLOGY: 3000
      patients with symptomatic laparoscopic cholecystectomy scheduled for laparoscopic
      cholesystectomy were included in the study. 458 patients (201 men, 257 women;
      mean age, 57.7 +/- 14.6 yrs) were examined with endoscopic retrograde
      cholangiopancreatography for suspected common bile duct stones. The serum tests
      for liver function, including a measurement of aspartate aminotransferase,
      alanine aminotransferase, alkaline phosphatase, total bilirubin, direct
      bilirubin, gamma-glutamyltransferase and albumin were obtained on admission prior
      to the ultrasonography, and the endoscopic retrograde cholangiopancreatography.
      RESULTS: The six significant factors, including alkaline phosphatase, direct
      bilirubin, total bilirubin, aspartate aminotransferase, alanine aminotransferase
      and gamma-glutamyltransferase were identified by the univariate analysis and the
      multivariate logistic regression analysis which identified alkaline phosphatase
      and gamma-glutamyltransferase, as the two significant independent factors. A
      statistical model was developed with a formula of [formula: see text] A curve of
      receiver operating characteristics was constructed to identify an alkaline
      phosphatase level greater than 300 U/L or a gamma-glutamyltransferase level
      greater than 420 mU/mL which would have both higher sensitivity and specificity.
      CONCLUSIONS: Biochemical tests can be a significant aid to the clinician's
      decision-making when predicting the presence of common bile duct stones in
      patients with gallstones.

PMID- 11462889
TI  - Routine testing of liver function after biliary-enteric anastomosis has no
      clinical relevance.
AB  - BACKGROUND/AIMS: Patients who had a biliary-enteric anastomosis often have
      elevated liver function tests. The aim of this study was to investigate whether
      elevated liver function tests are associated with recurrent episodes of
      cholangitis. METHODOLOGY: Thirty-two patients, who received a biliary-enteric
      anatomosis for benign biliary disease were evaluated. Follow-up consisted of the
      patient's history, physical examination, determination of liver function tests,
      ultrasonography and hepatobiliary scintigraphy using 99mTc-HIDA. RESULTS: Median
      duration of follow-up was 45 months (range: 1-192) and liver function tests were
      elevated in 22 patients (69%) at some time during follow-up. Dilated intrahepatic
      ducts were found in 3 of 30 patients (10%), all of whom had elevated liver
      function tests at follow-up. Delayed passage from the liver was observed using
      scintigraphy in 10 (31%) of the patients. Seven patients (22%) experienced one
      episode of cholangitis and none experienced more than one episode. Multivariate
      analysis showed that male sex was an independent risk factor for elevated liver
      function tests (odds ratio: 10.9; P < 0.05). For cholangitis, no risk factors
      could be identified. CONCLUSIONS: It is concluded that elevated liver function
      tests are relatively common after a biliary-enteric anastomosis for benign
      biliary tract disease and are not predictive of the occurrence of cholangitis.
      We, therefore, recommend omitting routine laboratory screening for elevated liver
      function tests in the follow-up of a biliary-enteric anastomosis.

PMID- 11462890
TI  - Atypical primary sclerosing cholangitis cases associated with unusual
      pancreatitis.
AB  - BACKGROUND/AIMS: We encountered one group of primary sclerosing cholangitis cases
      which met classic criteria, but demonstrated better clinical courses.
      METHODOLOGY: We evaluated the clinical characteristics of several cases of
      primary sclerosing cholangitis, especially those associated with chronic
      pancreatitis. RESULTS: Of a total of 25 cases, eight had a background of
      pancreatitis with unusual irregularly segmental or diffuse narrowing features on
      pancreatography. Abdominal ultrasonography and computed tomography also revealed
      segmental or diffuse enlargement of the pancreas. Pathological findings of
      surgical specimens in two cases pointed to lymphoplasmacytic sclerosing
      pancreatitis. The walls of the lower biliary ducts were also thickened with a
      similar appearance to the pancreatic ducts. In seven cases, cholangiography
      displayed stenosis of the lower part of the common bile duct and in one case,
      only the hepatic hilar region was affected. In this case both biliary and
      pancreatic lesions responded to steroid therapy simultaneously. One case
      developed hepatic hilar stenosis four months after a lesion in the lower part of
      the common bile duct had disappeared. The cases of primary sclerosing cholangitis
      with pancreatitis demonstrated better clinical courses than did typical cases of
      primary sclerosing cholangitis. Six cases were characterized by autoimmunological
      abnormalities. CONCLUSIONS: We concluded that similar etiological agents might
      impact on both the pancreas and biliary tract, either simultaneously or in
      sequence. We propose new criteria for these atypical primary sclerosing
      cholangitis cases.

PMID- 11462891
TI  - Intraluminal brachytherapy and selfexpandable stents in nonresectable biliary
      malignancies--the question of long-term palliation.
AB  - BACKGROUND/AIMS: To evaluate the effect of a combination of intraluminal
      brachytherapy and metallic stent implantation in the treatment of patients with
      nonresectable biliary tumors. METHODOLOGY: Thirty-two patients aged 41-80 years
      with nonresectable biliary malignancies--Klatskin's tumor (n = 17), gallbladder
      carcinoma (n = 11) and carcinoma of papilla Vateri (n = 4)--were treated with a
      combination of intraluminal brachytherapy (source Ir192, high-dose radiation
      regimen, total dose 30 Gy) and metallic stent implantation. Intraluminal
      brachytherapy and stent insertion (metallic, spiral-Z stent) were performed
      percutaneously in all patients. RESULTS: The mean survival in patients with
      Klatskin's tumor was 457 days (range: 64-1186; median: 358 days), in patients
      with gallbladder carcinoma 237 days (range: 92-609; median: 210 days) and in
      patients with carcinoma of papilla Vateri 850 days (range: 48-1518; median: 1277
      days). The rate of 2-year survival in these groups as 27, 0 and 50%,
      respectively. The survival time differed significantly at the 5% level. The mean
      time of stent patency was 418, 220 and 850 days, respectively. No complications
      related directly to intraluminal brachytherapy were observed. CONCLUSIONS:
      Intraluminal brachytherapy combined with stent implantation is a safe method and
      appears to prolong survival in inoperable patients with Klatskin's tumor and
      carcinoma of papilla Vateri compared with nontreated patients in previous
      studies. In contrast no similar effect should be expected in patients with
      gallbladder carcinoma.

PMID- 11462892
TI  - Surgical treatment for congenital biliary dilatation, with or without
      intrahepatic bile duct dilatation.
AB  - BACKGROUND/AIMS: The incidence of postoperative cholangitis differs between
      patients with and those without congenital intrahepatic bile duct dilatation. The
      aim of this study was to evaluate comparatively the treatment results in these
      two patients groups. METHODOLOGY: Forty-eight patients were classified into those
      with (dilated type) and those without (nondilated type) intrahepatic bile duct
      dilatation. The surgical procedure used, clinical manifestation, and cell
      kinetics (proliferating cell nuclear antigen labeling index, PCNALI) of bile duct
      epithelium were examined with respect to the incidence and course of
      postoperative cholangitis. RESULTS: Nineteen patients were classified as the
      dilated type, and the other 29 patients were the nondilated type. In the dilated
      type group, hepaticoduodenostomy was performed on five patients,
      hepaticojejunostomy (Roux-en-Y method) on eight and jejunal interposition on six.
      Among the 29 nondilated-type patient, hepaticoduodenostomy was performed on 19
      patients, hepaticojejunostomy (Roux-en-Y method) on seven, and jejunal
      interposition on three. Hepatectomy was performed in one dilated-type adult
      patient with marked cholangiectasia in the left hepatic lobe. The incidence of
      postoperative cholangitis was 26.3% (5/19) in the dilated-type group and 6.9%
      (2/29) in the nondilated-type group. The clinical manifestation was generally
      mild in the nondilated-type patients. However, among the adult dilated-type
      patients, on whom jejunal interposition had been performed, there were two
      patients who required additional surgery for the treatment of cholangitis that
      occurred postoperatively. The PCNALI in the bile duct epithelium was 13.9% for
      the dilated-type and 8.8% for the nondilated-type groups, respectively.
      CONCLUSIONS: Jejunal interposition for biliary reconstruction seems a
      contraindicated maneuver for adult dilated-type patients, because of the possible
      development of postoperative cholangitis. The cellular proliferating activity in
      the bile duct epithelium of the patients of both the dilated and nondilated type
      was significantly increased compared to that of a control group. Consequently,
      the extrahepatic bile duct might have to be removed in patients with
      pancreaticobiliary maljunction regardless of the presence or absence of biliary
      dilatation.

PMID- 11462893
TI  - Evaluation of immune response in patients after open or laparoscopic
      cholecystectomy.
AB  - BACKGROUND/AIMS: Laparoscopic cholecystectomy is a so called mini-invasive
      surgical procedure, and on this basis, we investigated whether and how the immune
      response is modified in patients after laparoscopic cholecystectomy compared to
      patients who underwent open cholecystectomy. METHODOLOGY: In a prospective,
      nonrandomized trial, 35 patients underwent laparoscopic cholecystectomy and 31
      open cholecystectomy. Immune activity (neutrophils, total lymphocytes, lymphocyte
      subpopulations, human leukocyte antigen (HLA-DR), interleukin 6, skin Multitest)
      was evaluated before surgery and respectively, 1, 3, and 6 days postoperatively.
      RESULTS: One day after surgery, an increase in interleukin 6 (P < 0.01) was noted
      in patients who had undergone open cholecystectomy, while this parameter was
      almost unchanged in patients with laparoscopic cholecystectomy. Moreover, skin
      tests showed a hypo or anergic response in the majority (81.8%) of open
      cholecystectomy patients compared to laparoscopic cholecystectomy patients
      (10.5%), (P < 0.01). Finally, monocyte antigen HLA-DR was also reduced in open
      cholecystectomy patients (P < 0.05). In this group, we noted 2 cases (6.45%) of
      respiratory tract infection. CONCLUSIONS: Even though laparoscopic
      cholecystectomy requires a longer surgery, it reduces postoperative pain, and
      hospitalization. It also facilitates rapid recovery, a return to normal activity,
      avoids postoperative immunosuppression and shows a better postoperative morbidity
      compared to open surgery.

PMID- 11462894
TI  - Biliary cystadenocarcinoma with superficial spread to the extrahepatic bile duct.
AB  - We report a case of biliary cystadenocarcinoma of the liver with superficial
      spread to the extrahepatic bile duct. Preoperative endoscopic retrograde
      cholangiography revealed communication between a 4.5-cm cyst in segment 4 of the
      liver and the bile duct. From the findings obtained by peroral cholangioscopy and
      intraoperative cholangioscopy, the granular mucosa in the bile duct was diagnosed
      as superficially spreading cancer. The right posterior segmental bile duct and
      the right anterior segmental bile duct were resected at the point where the
      spread of cancer was no longer traceable and left lobectomy plus caudate
      lobectomy was carried out. This achieved radical resection, leaving the resected
      margin of the bile duct free from cancer. Histopathologically, well
      differentiated papillary adenocarcinoma was found on the inner surface of the
      cyst, and the cancer had superficially spread from the cyst to the extrahepatic
      bile duct via the 2.5-mm diameter communication between the cyst and bile duct.
      The cancer was limited only to the mucosal layer all over the lesion. When
      performing radical surgery for biliary cystadenocarcinoma, it is recommended that
      cholangioscopy be performed to examine whether the cancer has superficial spread
      to the extrahepatic bile duct or not. Bile duct resection should be carried out,
      depending on the extent of the superficial spread, so that the resected margin of
      the bile duct is free from cancer.

PMID- 11462895
TI  - Multiple mucosal lesions in the duodenum: exploring the potential clinical
      backgrounds and concurrent diseases.
AB  - BACKGROUND/AIMS: Multiple mucosal lesions of the duodenum (MMLD), presenting with
      multiple mucosal redness and ulcers with or without blood clots in the proximal
      duodenum, may be occasionally discovered during gastroduodenal endoscopy. This
      study was undertaken to investigate the clinical implications of MMLD.
      METHODOLOGY: Endoscopic pictures and charts of patients with MMLD were
      retrospectively reviewed. The endoscopic features of MMLD were recorded for both
      location and severity. The endoscopic severity of MMLD was defined as follows:
      Grade I: multiple mucosal redness; Grade II: multiple ulcers with clear base;
      Grade III: multiple ulcers with reddish base or fresh blood clot coating.
      RESULTS: A total of 229 (1.08%) MMLD events in 207 patients were identified out
      of a total of 21,223 upper gastrointestinal endoscopies. Common backgrounds of
      patients with MMLD included diabetes, hypertension, and some chemical exposure,
      such as cigarettes, alcohol, nonsteroidal anti-inflammatory drugs and anti
      Helicobacter pyloric regimens. Common concurrent diseases included peptic
      disease, sepsis, malignancy, renal insufficiency, and portal hypertension. MMLD
      associated with sepsis usually involved only the second portion of the duodenum,
      but when associated with nonsteroidal anti-inflammatory drugs was less often only
      involved with the second portion. MMLD with renal insufficiency was less prone to
      involve the bulb alone. Diabetes-related MMLD tended to present with mild
      severity as defined by Grade I, H. pylori infection with Grade II, and renal
      insufficiency and portal hypertension with higher severity such as Grade III.
      Nine patients had fatal outcomes due to uncontrolled concurrent diseases, other
      than MMLD. CONCLUSIONS: MMLD, an uncommon occurrence in endoscopy, can develop
      from several clinical settings. When encountering MMLD while performing
      endoscopy, the best policy is to search and correct the concurrent diseases as
      early as possible.

PMID- 11462896
TI  - Indications for posthepatectomy hepatic vein reconstruction from functional and
      morphological studies: clamping test and hepatic vein branch distribution
      determined by three-dimensional computed tomography.
AB  - BACKGROUND/AIMS: Indications for hepatic vein reconstruction for preserving
      remnant liver function after hepatectomy were assessed using the clamping test
      and the findings of preoperative 3D-CT (3-dimensional computed tomography).
      METHODOLOGY: Fifteen patients who underwent hepatectomy for malignant tumors in
      segment VII or VIII, or both, were examined with preoperative 3D-CT and an
      intraoperative clamping test. RESULTS: On the basis of changes in right hepatic
      venous pressure during clamping, we classified all patients into 3 types: the
      persistent elevation type (P-type, 8 patients), the no elevation type (N-type, 3
      patients) and the transitory elevation type (T-type, 4 patients). Hepatic venous
      hemoglobin oxygen saturation (ShvO2) decreased significantly in the P type but
      hardly changed in the T and N types during the clamping test. Both the inferior
      right hepatic vein (IRV6) and the tributary of the middle hepatic vein draining
      segment V (MV5) were detected by preoperative 3D-CT in the T and N types.
      CONCLUSIONS: Assessments of hepatic vein branch distribution using preoperative
      3D-CT served to predict the results of the hepatic vein clamping test. The
      results of preoperative 3D-CT were useful as indications for hepatic vein
      reconstruction.

PMID- 11462897
TI  - IGF-I triple helix strategy in hepatoma treatment.
AB  - BACKGROUND/AIMS: To investigate the effect of gene therapy for hepatocellular
      carcinoma based on inhibition of cellular IGF-I expression, the technique of IGF
      I triple helix was investigated in mice developing programmed hepatoma.
      METHODOLOGY: mhAT1F1 mouse hepatoma cell line was transfected in vitro with IGF-I
      triple helix expression vector (pMT-AG-TH) or with IGF-I antisense expression
      vector (pMT-Anti-IGF-I). 10 x 10(6) transfected cells of either triple helix or
      antisense type were inoculated intraperitonealy into transgenic ATIIITB6 mice
      developing genetically programmed hepatoma (mice die between the age of 6 and 7
      months). In parallel, human cell cultures established from surgically removed
      hepatomas were investigated. RESULTS: mhAT1F1 and human primary cell cultures,
      transfected with pMT-AG-TH or pMT-Anti-IGF-I vectors resulted in total inhibition
      of IGF-I demonstrated by immunocytochemical and Northern blot techniques.
      Transfected cells changed their phenotype and recovered major histocompatibility
      complex I expression showed by fluorescence-activated cell sorting analysis and
      Western blot. Moreover, two phenomena were observed in IGF-I "antisense" or
      "triple helix" transfected cells: 1) the apoptosis, demonstrated by TUNEL
      technique; 2) the presence of IL-6 simultaneously with disappearance of tumor
      necrosis factor-alpha and IL-10, investigated by reverse transcriptase-polymerase
      chain reaction technique. In in vivo experiments, injection of murine transfected
      cells into mice in terminal-phase prolonged their survival 3-4 months in 100% of
      cases, as well in "antisense" group (8/8) as in "triple helix" group (10/10).
      CONCLUSIONS: Injection of hepatoma cells transfected with IGF-I triple helix
      expression vector, and showing immunogenic and apoptotic characteristics, can
      constitute an effective cellular therapy against hepatocellular carcinoma.

PMID- 11462898
TI  - The effect of portal hypertension on expression of gastric mucin mRNA in rats.
AB  - BACKGROUND/AIMS: Gastric mucin, a principal component of gastric mucus, is
      thought to play an important role in protecting gastric mucosa and maintaining
      the homeostasis of the gastric mucosa. Our previous studies have demonstrated
      that the contents of gastric mucin were decreased in rats with portal
      hypertension. Thus, the purpose of this present study was designed to confirm the
      effect of portal hypertension on the expression of gastric mucin mRNA and to
      localize gastric mucin mRNA production site in rats. METHODOLOGY: Portal
      hypertension was induced experimentally by partial ligation of the portal vein in
      Wistar rats. The severity of gastric mucosal lesions was evaluated
      macroscopically by a gross ulcer index. We simultaneously measured the levels of
      mRNA in the gastric tissues of control and portal hypertension rats by reverse
      transcription-polymerase chain reaction, Southern blot hybridization, and in situ
      hybridization. RESULTS: The damage to gastric mucosa was found to be prominently
      greater in the portal hypertension rats compared to the control (P < 0.01). The
      expression of mucin mRNA was significantly reduced in portal hypertension rats
      compared to the control using the reverse transcription-polymerase chain reaction
      and Southern blot hybridization (both P < 0.01). In situ hybridization showed
      that mucin mRNA was localized primarily in the gastric submucosa and mucosa,
      particularly in the surface mucous and the gland mucous cells. CONCLUSIONS: Our
      results reveal that portal hypertension would cause a decrease in mucin mRNA, and
      it would be helpful in understanding the mechanism of gastric mucosal mucin
      alteration in portal hypertension and the pathogenesis of portal hypertension
      gastropathy. Furthermore, it may provide the strategy in the prevention and
      therapy of portal hypertension gastropathy.

PMID- 11462899
TI  - The role of liver transplantation in patients with Caroli's disease.
AB  - Caroli's disease, characterized by segmental or diffuse dilation of the
      intrahepatic biliary ducts, is a rare disease which is difficult to treat. The
      course of the disorder is characterized by recurrent episodes of cholangitis and
      hospital stays, with a consequent loss of quality-of-life and productive
      capacity, often ending in death due to uncontrolled infection. Endoscopic
      drainage of the bile duct, percutaneously or surgically, is palliative, and
      presents bad results in the follow-up of these patients. Orthotopic liver
      transplantation appears to be an effective curative option for the treatment of
      patients with Caroli's disease associated to complications. The authors present
      the course of two cases of this disease, associated with congenital fibrosis of
      the liver worsened by repeated episodes of cholangitis, submitted to orthotopic
      liver transplantation.

PMID- 11462900
TI  - Mantle cell lymphoma of the rectum at an early stage: a case report.
AB  - We report a very rare early-stage case of mantle cell lymphoma, which arose from
      the rectum. A 60-year-old man presented with a small elastically hard polypoid
      lesion in the rectum. The lesion was 1.2 x 1.2 cm in size. As a preoperatively
      barium enema and endoscopy suggested a benign tumor of the rectum, he underwent
      local excision of a rectal polypoid mass transanally under spinal anesthesia.
      However, histological examination revealed a malignant lymphoma, because the
      lesion was histologically characterized by solid growths of small to medium-sized
      round cells. Furthermore, immunohistochemical tests revealed B-cell marker
      positivity and CD5 positivity, but cyclin D1 negativity. Since it was reported
      that lymphomas with a mantle cell lymphoma morphology and CD5 expression, but
      without cyclin D1 overexpression, exist in about 10% of mantle cell lymphoma
      cases, we diagnosed his disease as mantle cell lymphoma. To our knowledge, this
      is the first reported case of an early-stage mantle cell lymphoma, originating
      from the rectum.

PMID- 11462901
TI  - Spontaneous ruptured middle colic artery aneurysm with concurrent renal cell
      carcinoma.
AB  - We present the first reported case of spontaneous ruptured middle colic artery
      aneurysm in a patient who has concurrent hypervascular tumor which has a
      potential for rupturing. A 68-year-old Japanese man was admitted with abdominal
      pain and hypervascular renal tumor which developed in the subcapsular cortex and
      protruded outward. The next morning after admission, anemia rapidly progressed
      and severe abdominal pain developed. Emergency laparotomy was performed for a
      preliminary diagnosis of ruptured hypervascular renal tumor. However, the renal
      tumor was not ruptured but a ruptured middle colic artery aneurysm was found. The
      aneurysm measured 3.0 x 2.0 cm in greatest diameter and was resected. Three weeks
      later, nephrectomy for hypervascular renal tumor was electively performed.
      Histologically, the tumor was clear cell carcinoma. In the present case, the
      diagnosis of ruptured middle colic artery was extremely difficult.

PMID- 11462902
TI  - Peroral jejunoscopy for treating stenosis of hepaticojejunostomy after
      pancreatoduodenectomy.
AB  - A 72-year-old woman suffered from relapsing cholangitis after pylorus-preserving
      pancreatoduodenectomy for chronic pancreatitis. The common hepatic duct had been
      anastomosed to the jejunum 8 cm distal to the duodenojejunostomy. Peroral
      jejunoscopy showed a severe stenosis of the hepaticojejunostomy, which was
      endoscopically enlarged by means of electroincision and balloon dilation,
      subsequently. No procedure-related complications occurred. The patient has been
      asymptomatic for 34 months. Most of the strictures of bilioenterostomy are
      reportedly treated by surgical revision, the percutaneous transhepatic approach,
      or the percutaneous transjejunal approach. Endoscopic treatment may be attempted
      in cases in which the postoperative anatomy potentially allows endoscopic access,
      because of its minimal invasiveness and effectiveness.

PMID- 11462903
TI  - Surgical treatment of synchronous hepatocellular and esophageal carcinoma: case
      report and review of literature.
AB  - Simultaneous presentation of hepatocellular carcinoma and esophageal carcinoma is
      rare. Few cases have been reported as surgically curable. We treated a caucasian
      man of 68 years who presented a voluminous hepatocellular carcinoma in the right
      lobe of the liver and a superficial squamous cell carcinoma of the middle third
      of the esophagus. Both tumors seemed curable with surgery. We adopted a treatment
      consisting of two steps: 1) curative hepatic right trisegmentectomy; 2) three
      months later transhiatal esophagectomy. Two units of blood were transfused for
      both operations. Simultaneous hepatectomy and esophagectomy have been published
      in seven cases. We opted for resecting the tumors in two distinct procedures to
      lower the operative risk. Because of the large size of the hepatocellular
      carcinoma and the small size of the esophageal carcinoma, hepatectomy was
      performed first. The delay between the two interventions did not compromise the
      prognosis that is actually dependent of the hepatocellular carcinoma.

PMID- 11462904
TI  - A rare case of alpha-fetoprotein-producing early gastric cancer.
AB  - Most of the alpha-fetoprotein-producing gastric cancer is advanced at the time of
      presentation, and alpha-fetoprotein-producing early gastric cancer is extremely
      rare. Alpha-fetoprotein-producing early gastric cancer was confirmed by
      immunohistochemistry and serum analysis of alpha-fetoprotein concentration. Alpha
      fetoprotein carbohydrate chain microheterogeneity was further evaluated by lectin
      binding specificity. A 71-year-old-male patient underwent total gastrectomy due
      to a depressed type of gastric cancer in the upper third of the stomach. There
      was no evidence of synchronous liver metastasis and hepatitis. Histological
      examination revealed that the tumor invasion was limited to the submucosal layer,
      and that the tumor consisted of both well-differentiated, papillo-tubular growth
      areas and trabecular and medullary growth areas resembling hepatoid carcinoma.
      Immunohistochemically, alpha-fetoprotein and cytokeratin localization were
      confirmed in the cancer cells, whereas simultaneous localization of
      carcinoembryonic antigen, carbohydrate antigen 19-9, and human chorionic
      gonadotropin could not be observed. The elevated preoperative serum alpha
      fetoprotein concentration (113 ng/mL) promptly decreased to and remained within
      normal levels postoperatively (3.6 ng/mL). The predominance of a strong-bound
      fraction with lectin, which was demonstrated by lens culinalis agglutinin
      affinity chromatography, suggests that the alpha-fetoprotein carbohydrate chain
      species in the present case was a hepatic type. The patient received adjuvant
      intravenous chemotherapy consisting of 5-fluorouracil and cisplatin, and has been
      further supported by oral 5-fluorouracil administration. The patient has been
      disease free for 15 months following surgery. We report here a rare case of alpha
      fetoprotein producing early gastric cancer. The alpha-fetoprotein carbohydrate
      phenotype analysis helps to consider the primary differentiation of alpha
      fetoprotein-producing gastric cancer.

PMID- 11462905
TI  - Quantitative analysis of telomerase activity: a potential diagnostic tool for
      colorectal carcinoma.
AB  - BACKGROUND/AIMS: We describe the results of the application of the nonradioactive
      F-TRAP (fluorescence-based telomeric repeat amplification protocol) assay for the
      diagnosis of colorectal carcinoma(s). We also investigated whether the level of
      telomerase activity in colorectal carcinoma can be distinguished from that in
      normal colorectal tissue or benign colorectal tumors, in which the presence of
      telomerase activity has also been demonstrated. In addition, we also investigated
      whether it could be a potential tumor progression marker. METHODOLOGY: The F-TRAP
      assay was performed, using biopsy specimens obtained from colonoscopic
      examinations, including 20 colorectal carcinoma, 10 tubular adenoma and 20
      adjacent colorectal normal tissue specimens. In 15 carcinoma cases, the
      correlation between telomerase activity level and clinicopathological parameters
      was analyzed. RESULTS: The results showed that the level of telomerase activity
      in colorectal carcinomas (88.71 +/- 92.1 units; mean +/- SD) was much higher than
      that in normal colorectal tissues (3.34 +/- 8.57 units) or adenomas (7.8 +/-
      10.27 units). By quantifying the level of telomerase activity using the F-TRAP
      assay, colorectal carcinomas can be distinguished from normal colorectal tissue
      or colorectal benign tumors. However, no significant correlation was observed
      between telomerase activity levels and clinicopathological parameters such as
      depth of tumor invasion, lymphatic and/or venous involvement, and regional lymph
      node metastasis and Dukes' stage. CONCLUSIONS: Quantitative analysis of the level
      of telomerase activity using the F-TRAP assay provides a useful diagnostic tool
      for colorectal carcinoma, but it would not be useful as a tumor progression
      marker.

PMID- 11462906
TI  - Clinicopathological analyses of advanced colorectal cancers of different sizes-
      especially those of 20 mm or less in diameter.
AB  - BACKGROUND/AIMS: Many small cancers of the flat type can now be detected, and
      many advanced cancers of the flat type have been discovered. In this study, to
      clarify the clinicopathological characteristics of small advanced cancers,
      advanced cancers of 20 mm or less in diameter were compared with those of other
      sizes. METHODOLOGY: Patients with advanced colorectal cancer (n = 865) were
      divided into four groups on the basis of cancer diameter as follows: Group A (20
      mm or less), 21 patients; Group B (21-60 mm), 581 patients; Group C (61-100 mm),
      215 patients; and Group D (101 mm or more), 48 patients. These groups were
      compared for various clinicopathological findings. RESULTS: The depth of invasion
      was muscularis propria in 14 cases and subserosa in 7 cases. In Group A, cancer
      was histologically well-differentiated in 8 cases, moderately differentiated in
      12 cases, and mucinous in one case. Six cases (28.6%) in Group A had lymph node
      metastasis (N1). In Group A, one patient had multiple liver metastasis and all of
      the other cases were assessed as R0 resection. CONCLUSIONS: Most small advanced
      colorectal cancers of 20 mm or less in diameter can be regarded as quasi-early
      cancers, but some have the potential for high malignancy, and for these,
      reduction surgery cannot be used.

PMID- 11462907
TI  - Diagnosis and treatment of bleeding colonic diverticula.
AB  - BACKGROUND/AIMS: Colonic diverticula are the most frequent cause of major lower
      intestinal bleeding and pose a diagnostic and therapeutic challenge to the
      attending physician. Emergency surgical resection is associated with a high
      mortality and morbidity and patients who will stop bleeding spontaneously cannot
      be distinguished from those who will continue to bleed. Our aim was to evaluate
      the efficacy of barium enema as a sole less invasive treatment option for severe
      diverticular bleeding. METHODOLOGY: We evaluated 102 patients admitted with
      colonic diverticular bleeding, from 1993 to 1997, who needed transfusion of 2 or
      more units of blood. We compared the clinical efficacy of surgical resection,
      conservative treatment, and therapeutic barium enema with regard to the cessation
      of bleeding, morbidity, mortality, and rebleeding rate. The therapeutic
      strategies used after further episodes of bleeding were also registered. RESULTS:
      Transfusion requirements were highest in patients who underwent surgical
      treatment, while the least amount of blood was required by the barium enema group
      (6.9 +/- 3.1 vs. 3.6 +/- 1.5 units of blood). However, the quantity of transfused
      blood did not correlate with the initial hemoglobin level, which was highest in
      the conservative treatment group and lowest in the operative group (9.0 +/- 1.2
      vs. 8.1 +/- 1.3 g/dL). These data support the fact that the most severe bleeding
      would necessitate surgical resection and that therapeutic barium enema may be
      considered more effective than conservative treatments. With regard to the
      outcome of treatment, conservative treatment led to a rebleeding rate of 43.3%,
      which differed significantly from a 15.9% rebleeding rate after therapeutic
      barium enema (P = 0.009). No rebleeding was registered in surgically treated
      patients. Sixty percent of patients in whom therapeutic barium enema failed were
      treated by colonic resection without mortality, while 77% of patients who had
      rebleeding after conservative treatment were successfully treated with barium
      enema. Overall, barium enema was the most frequently applied second-line
      treatment (56.5%). The mortality after surgery was significantly higher than that
      after other treatment modalities (33% vs. 1%; P = 0.0001). CONCLUSIONS: If
      diverticular bleeding is clinically suspected as the cause of major lower
      intestinal hemorrhage, barium enema is a more promising alternative than
      conservative treatment because of diagnostic and therapeutic importance in the
      long-term. In the event of urgent secondary surgery following the failure of
      barium enema to stop bleeding, we recommend a sigmoidoscopy and, optionally, an
      angiography before surgery in order to first localize the bleeding. We conclude
      that therapeutic barium enema is the treatment of choice for the first bleeding
      episode, while surgical resection should be performed if rebleeding occurs.

PMID- 11462908
TI  - Distinct relationship between polypoid growth type and sporadic colorectal
      carcinomas with microsatellite instability.
AB  - BACKGROUND/AIMS: This study was carried out to clarify whether colorectal
      carcinomas with MSI (microsatellite instability) is correlated with growth types
      of invasive carcinomas. METHODOLOGY: Samples of tumor tissue and adjacent normal
      mucosa were obtained from 45 patients with sporadic advanced colorectal cancer.
      The MSI was assessed by the mobility shift assay of microsatellite and VNTR
      (variable numbers of tandem repeat) alleles using 12 markers. Tumors with four or
      more positive loci were determined to be MSI positive. The polyadenine tract
      (A)10 of the third exon in TGF beta RII was also assessed by mobility shift assay
      of DNA fragments amplified with primers. Histological examination was performed
      to divide all tumors into polypoid growth carcinoma and nonpolypoid growth
      carcinoma, according to Shimoda et al.'s classification. RESULTS: Ten of 11 cases
      with MSI had a 1-base pair deletion in a polyadenine tract in the TGF beta RII
      gene. Fifteen cases showed polypoid growth and 30 cases indicated nonpolypoid
      growth. There were 9 polypoid growth cases and 2 nonpolypoid growth cases with
      MSI, while there were 6 polypoid growth cases and 28 nonpolypoid growth cases
      without MSI. Colorectal cancer cases with MSI had a significantly higher
      incidence of cases with polypoid growth (9/11) compared to those without MSI
      (6/34) (P = 0.0004). CONCLUSIONS: Sporadic colorectal carcinomas with MSI tend to
      show a polypoid growth type. We think that there are two types including "adenoma
      carcinoma sequence" type and "RER" type in colorectal carcinomas that show
      adenoma-carcinoma progression.

PMID- 11462909
TI  - Chemotherapy of nonoperable colorectal liver metastases.
AB  - Biomodulated 5-fluorouracil-based therapy is the mainstay of treatment for
      advanced colorectal cancer. Patients with advanced disease do better with
      chemotherapy than they do without, but the overall survival in these patients is
      still poor. Combination of infusional and bolus 5-fluorouracil/folinic acid
      (leucovorin) regimens with newer agents, such as CPT-11 and oxaliplatin, in the
      fist-line treatment of patients with advanced colorectal cancer, has yielded
      increased response rates and progression-free survivals. In the case of CPT-11
      this has also led to an increase in overall survival. Improved therapy
      combinations and the delivery of the therapy directly to the liver by hepatic
      arterial infusion, either alone or in combination with intravenous delivery, all
      herald an improvement in the clinical outcome of patients with nonoperable liver
      metastases. These patients should be offered the best chemotherapy option
      available coupled, where appropriate, with liver resection.

PMID- 11462910
TI  - Surgical controversies in the treatment of recurrent achalasia of the esophagus.
AB  - BACKGROUND/AIMS: Surgery remains the first choice for achalasia of the esophagus
      with good results in 90% of cases. METHODOLOGY: We studied the cause of failure
      for surgical treatment and the results of a second operation in 20 patients that
      were followed up for at least three years. RESULTS: The results were good in 70%
      of the cases. CONCLUSIONS: To improve this procedure, according to the authors,
      it is essential for a careful presurgery evaluation, an early reoperation in case
      of failure and a careful surgical technique in order to avoid periesophageal
      sclerosis.

PMID- 11462911
TI  - Epiphrenic diverticula, esophageal carcinoma and esophagopleural fistula.
AB  - A case report of a patient with two epiphrenic diverticula and a squamous cell
      carcinoma within one of them is presented. Moreover, a pleural empyema and an
      esophagopleural fistula appeared following the neoplasic diverticulum
      perforation. Only a few cases have been previously described in the English
      language literature. An additional one is now presented.

PMID- 11462912
TI  - Importance of proliferation markers in gastrointestinal carcinoid tumors: a
      clinicopathologic study.
AB  - BACKGROUND/AIMS: Carcinoid tumors are common tumors in the gastrointestinal
      tract. Certain criteria such as the depth of invasion, the localization, the
      tumor size, the mitotic index and the pattern of ploidy are used to determine the
      potential biological behavior of these tumors some of which might be malignant.
      The goal of this study was to assess the prognostic significance of proliferation
      markers (Ki67 and PCNA) in carcinoid tumors by using immunohistochemistry.
      METHODOLOGY: An immunostaining in 37 carcinoid tumors arising in various
      locations of the gastrointestinal tract was performed. The best stained area was
      selected and 1000 neoplastic cells were counted in order to determine the
      proliferation index in each case. RESULTS: The results of proliferation index
      were compared with the depth of invasion, the embryologic type, the tumor size,
      the presence of metastases and disease-free survival by using statistical
      methods. The Ki67 tumor proliferation index in the tumors > 2.1 cm was
      significantly different from the tumors < or = 2 cm (P = 0.032). CONCLUSIONS: The
      presence of significant correlation between Ki67 positivity and the tumor size
      might suggest that Ki67 antibody can be useful for the determination of potential
      behavior of gastrointestinal carcinoid tumors.

PMID- 11462913
TI  - A noninvasive H. pylori stool antigen assay to detect H. pylori infection of in
      vivo BALB/c mice models.
AB  - BACKGROUND/AIMS: Previous tests for H. pylori infection status of mice have
      required sacrificing the small host for histological evaluation. We thus aim to
      determine whether a noninvasive HpSA (H. pylori-specific stool antigen assay)
      could be applied to detect H. pylori infection in living mice. METHODOLOGY: A
      total of 60 BALB/c specific pathogen-free mice were used, 20 per control group
      and 40 per exposed group, the exposed group being challenged with H. pylori
      isolates. In both groups, the stool samples of each mouse were collected before,
      7 days, and 4 weeks after the challenge with H. pylori isolates in the exposed
      group. All the stool samples were processed with HpSA to detect the presence of
      H. pylori infection. Four weeks after the inoculation of the exposed group and no
      inoculation in the control group, each mouse received gastrectomy for histology
      to judge the presence of H. pylori. RESULTS: None of the mice had a positive
      histology in the control group. Five BALB/c mice expired due to H. pylori
      inoculation in the exposed group. Four weeks after inoculation, 85.7% (30/35) of
      the BALB/c mice achieved the H. pylori infection. Applying the stool samples
      collected on the 7th day and selecting cutoff point as 0.2, the sensitivity and
      specificity of HpSA to detect the H. pylori colonization achieved as 100% and
      88%, respectively. The 4th week stool samples for HpSA achieved a high
      sensitivity as 96.6% and specificity as 96% to detect H. pylori infection rate,
      while choosing cutoff point as 0.20. CONCLUSIONS: HpSA can be an effective tool
      without subject lethality to detect H. pylori infection in BALB/c mice model.

PMID- 11462914
TI  - New aspects of prognostic factors in adenocarcinomas of the small bowel.
AB  - BACKGROUND/AIMS: Primary small bowel tumors are rare and the prognosis is
      generally considered to be poor. Histologically chiefly adenocarcinomas are
      reported. The surgeon is challenged in their treatment, because of the
      infrequency, unspecific symptoms and delay in diagnosis. Retrospectively we
      investigated the surgical therapy, combined morbidity, survival rates and
      prognostic factors in a large series of primary adenocarcinomas of the small
      bowel at a single surgical center. METHODOLOGY: Between 1985 and 1998, 94
      patients with a primary tumors of the small bowel (malignant n = 62 [65.9%],
      benign n = 32 [34.1%]) were operated on. The subgroup of the adenocarcinomas (n =
      22) were considered for this study. RESULTS: The median follow-up is 8.4 years
      (range: 0.9-14.2 years). Sixteen patients had a follow-up more than 5 years. The
      main surgical procedure was a small bowel segment resection. Morbidity was 13.6%
      (only in patients with a duodenal tumors) and the 30-day mortality 5.6%. The
      estimated 2-year-survival rate was 66%, the 5-year-survival rate 45%. Univariate
      analysis identified the presence of the residual tumor (R-status) (P = 0.004),
      tumor stage according to the UICC (P = 0.01), lymph node metastasis (P = 0.007),
      distant metastasis (P = 0.001), lymphangiosis carcinomatosa (P = 0.001) and
      vascular invasion (P = 0.0008) as prognostic factors. CONCLUSIONS: A complete
      macroscopic and microscopic tumor resection including a systemic lymph node
      dissection has to be the aim of any curative surgical approach in patients with
      adenocarcinoma of the small bowel.

PMID- 11462915
TI  - Experience of laparoscopic management in 100 patients with acute abdomen.
AB  - BACKGROUND/AIMS: The decision to operate on a patient with acute abdominal pain
      comes to the mind of the surgeon if routine investigations fail to identify the
      cause. A negative laparotomy may have complications, while laparoscopy appears to
      be a valuable way to improve the accuracy of diagnosis of acute abdominal pain
      and offers a promising modality of treatment. METHODOLOGY: The study included 100
      patients with provisional diagnosis of acute abdomen after clinical examination
      and conventional diagnostic aids. All the patients have been subjected to
      diagnostic laparoscopy. RESULTS: Eight cases (8%) were managed by laparotomy
      following diagnosis by laparoscope (disturbed ectopic pregnancy), while 92 cases
      (92%) were managed laparoscopically which resulted in 81 cases (81%) of
      successful laparoscopic procedure (31 appendectomies, 19 cholecystectomies, 12
      ovarian cyst accident, and others) and 11 cases (11%) were converted to open
      surgery (4 gallbladder empyema, 2 appendicular mass, 2 intestinal obstruction,
      and others). Postoperative complications were two cases of wound infection
      managed conservatively (perforated appendix). The postoperative follow-up for six
      months was uneventful. CONCLUSIONS: Laparoscopic management of acute abdomen is a
      safe and effective method with the advantages of small scar, short hospital stay
      and early recovery.

PMID- 11462916
TI  - Idiopathic segmental infarction of the greater omentum as a cause of acute
      abdomen report of two cases and review of the literature.
AB  - The segmental infarction of the greater omentum is a rare cause of acute abdomen.
      Its etiology is uncertain although several predisposing factors have been
      underlined such as congenital venous anomalies, sudden change of position and
      substantial meal. The clinical picture simulates an appendicitis or
      cholecystitis, thus being difficult to make a preoperative diagnosis. However,
      ultrasonography or computed tomography scan can help us make this diagnosis and
      then we alternatively perform a conservative treatment, laparoscopic approach or
      resection by laparotomy. We present two cases, preoperatively diagnosed by
      ultrasonography and computed tomography scan that were treated by laparotomy
      resection. We also review the published cases in the medical literature.

PMID- 11462917
TI  - A rare type of lesser sac hernia.
AB  - We report herein the case of a female who developed a lesser sac hernia which was
      a rare type and was strangulated by a hole in the posterior layer of the lesser
      omentum. In our patient, abdominal computed tomography showed a loop of distended
      intestines among the liver, gallbladder and stomach. To our knowledge, there has
      been no previous report of transomental hernia exactly like our present case.

PMID- 11462918
TI  - Reactive oxygen metabolites and upper gastrointestinal diseases.
AB  - Reactive oxygen metabolites play an important role in the pathogenesis of
      gastroduodenal mucosal inflammation (mucosal ischemic injury and other models of
      mucosal damage induced by nonsteroidal anti-inflammatory drugs, ethanol, or H.
      pylori), peptic ulcer disease, and gastric cancer. H. pylori achieves its
      pathogenetic role by triggering an intense leukocyte infiltration of the gastric
      mucosa, and neutrophil activation provides a major source of reactive oxygen
      metabolites which can cause tissue damage mainly in the absence of antioxidants.
      H. pylori virulence factors promote release of a variety of
      chemoattractants/inflammatory mediators. Circulating leukocytes are recruited to
      sites of inflammation by a well-regulated and coordinated process that largely
      occurs in postcapillary venules. Adhesion molecules are expressed on the surface
      of endothelial cells and leukocytes serve to ensure an orderly sequence of cell
      to-cell interactions that sustain leukocyte adherence to vascular endothelium and
      the subsequent transendothelial migration into inflamed tissue. Transcriptional
      factors are involved in the expression of endothelial adhesion molecules, and
      regulation of activity of these factors (i.e., NF-kappa B) is a very attractive
      target for therapeutic interventions. Longstanding H. pylori-associated gastritis
      predisposes to gastric cancer development and reactive oxygen metabolites play a
      part in H. pylori-related gastric carcinogenesis. Various regimens of reactive
      oxygen metabolite scavengers appear to be new treatment strategies for upper
      gastrointestinal diseases.

PMID- 11462919
TI  - The intracorporeal autoorganic biofilter of portal blood in portal hypertension
      surgery.
AB  - BACKGROUND/AIMS: The authors present the new surgical treatment method for portal
      hypertension by means of intracorporeal autoorganic biofilter of portal blood at
      the portosystemic shunt pathway. The hepatized spleen is used as the organic
      biofilter of portal blood. METHODOLOGY: The experiments were carried out on 20
      mongrel dogs, both sexes, 18-20 kg of body weight. The animals were divided into
      the four equal groups. The comparative evaluation of portal hypertension
      treatment efficiency by means of several vascular portosystemic shunts were
      performed after the portal hypertension modeling. On the animals of groups I and
      II, the mesenterico-caval and splenorenal shunts were performed, respectively.
      The hepatized autospleen was involved in the portosystemic shunt pathway in the
      animals of group III. The animals of group IV served as controls. RESULTS: The
      reduction in perfusional pressure of the blood which flows to the liver led to
      damage of the organ's functional possibilities, significant disturbances to the
      hemodynamics and reduction of the liver detoxification possibilities,
      respectively, for several portocaval shunt creations during the portal
      hypertension model. On the other hand, the undetoxificated portal blood entrance
      into the system blood flow via the created shunt over the liver increased.
      CONCLUSIONS: The hepatized autospleen insertion into the portosystemic bloodflow
      gave us the opportunity to perform the dosage passing of portal blood into the
      systemic bloodflow and to maintain the pressure of the portal blood, which flows
      to the liver. Moreover, the hepatized autospleen has shown such specific liver
      functions as glucogenesis, albumin synthesis and others.

PMID- 11462920
TI  - Is resection for large hepatocellular carcinoma in cirrhotic patients beneficial?
      Study of 38 cases.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma in cirrhotic patients generally carries
      a poor prognosis either due to recurrence or to postoperative morbidity or both.
      Several factors affect the prognosis of hepatocellular carcinoma resection as
      presence of cirrhosis of the liver, tumor diameter and tumor capsulation.
      METHODOLOGY: Thirty-eight patients with large hepatocellular carcinoma greater
      than 5 cm with a background of cirrhotic liver were divided into two groups
      according to tumor diameter. Group A (n = 20) with tumors less than 10 cm in
      diameter, and group B (n = 18) with tumors larger than 10 cm. All patients
      underwent preoperative investigations including clinical laboratory tests,
      sonography, computed tomography, selective angiography and upper gastrointestinal
      endoscopy. All patients were subjected to different types of hepatic resection.
      RESULTS: A significant difference in tumor size, capsulation, and operation time
      were recorded between the two groups, of patients. No significant difference was
      detected between both groups regarding sex, age, viral markers, pathologic
      features, and Child classification. Hospital mortality occurred in 5% versus
      11.1% of both groups, respectively. Postoperative jaundice and ascitis occurred
      in 30%, 35% versus 44.4%, 72.0%, respectively (P < 0.005, P < 0.04). Late
      mortality occurred in 65% of patients in group A and in 77% of group B.
      Recurrence was detected in 42% of group A and 62% in group B. Recurrence after
      resection in capsulated tumors was significantly lower than in noncapsulated
      tumors in group A (P < 0.01), but not significant in group B. Also, survival rate
      in patients with capsulated tumors was significantly better in both groups (P <
      0.01) than that with noncapsulated tumors. CONCLUSIONS: Resection of
      hepatocellular carcinoma with diameter larger than 10 cm recorded bad prognosis
      regarding recurrence and mortality rates than tumors less than 10 cm. However,
      capsulated tumors gave better postoperative prognosis than noncapsulated ones.

PMID- 11462921
TI  - Oxidative stress in fulminant hepatic failure: comparison of two pig models with
      and without liver necrosis.
AB  - BACKGROUND/AIMS: No experimental study has clearly demonstrated how liver
      necrosis worsens the evolution of fulminant hepatic failure. Considering that
      several types of liver injury are associated with oxidative stress, we decided to
      measure plasma oxidative markers in two pig models of fulminant hepatic failure
      without and with liver necrosis. METHODOLOGY: Fulminant hepatic failure was
      produced in two groups of six pigs each by either total hepatectomy or complete
      hepatic devascularization. The following parameters were recorded before and
      during the course of hepatic failure: electrocerebral activity, plasma vitamin E,
      malondialdehyde and fluorescent protein-aldehyde adducts, total cholesterol,
      lactate-dehydrogenase, creatine phosphokinase, and ammonium. RESULTS: Despite
      comparable survival periods, hepatic necrosis was associated with earlier
      electrocerebral deterioration. Plasma concentration of malondialdehyde and
      fluorescent protein-aldehyde adducts rose and vitamin E content decreased in both
      groups. However, while in the group without liver necrosis the rates of
      cholesterol and vitamin E decay were identical, in the group with liver necrosis
      cholesterol concentration decreased less than vitamin E concentration, strongly
      indicating a true intravascular oxidation of vitamin E. Interestingly, in both
      models the rise of oxidative parameters preceded the development of cell injury.
      CONCLUSIONS: Oxidative stress, although present in both models, was significantly
      higher in the group with liver necrosis.

PMID- 11462922
TI  - Liver hemangioma revisited: current surgical indications, technical aspects,
      results.
AB  - BACKGROUND/AIMS: New developments regarding the diagnosis of liver hemangiomas,
      surgical indication and therapeutic options emerged recently. We reviewed our
      experience from the point of view of these modern developments. METHODOLOGY:
      Fifty-seven patients with liver hemangiomas were retrospectively studied. The
      relationship between size, symptoms and treatment was assessed. RESULTS:
      Indication for surgery was the size of the lesion in 5 patients, symptomatology
      in 48 and uncertain diagnosis in 4. Increase in size was noted in four patients.
      Six patients had associated intraabdominal benign or malignant pathology. The
      treatment of choice was enucleation. Postoperative complications were noted in 6
      patients and mortality was nil. In 3 patients the hemangiomas recurred and were
      reresected in 2. CONCLUSIONS: Hemangiomas should be resected when larger than 10
      cm and when they become symptomatic. With the modern diagnostic work-up,
      uncertainty of diagnosis as an indication for surgery should be rare. Surgery
      remains the main treatment, with a low morbidity and mortality if performed in a
      specialized hepatobiliary unit. Enucleation is the surgical option of choice. In
      selected cases laparoscopic enucleation can be performed with good results.

PMID- 11462923
TI  - Evaluation of hepatic functional reserve in rats with obstructive jaundice by
      asyaloglycoprotein receptor.
AB  - BACKGROUND/AIMS: Until now, there has been no adequate means of evaluating the
      liver functional reserve in cases with obstructive jaundice. 99mTC-GSA
      (99mTechnetium-DTPA-Galactosyl-human serum albumin) is a new liver-imaging agent
      which binds specifically to the asyaloglycoprotein-receptor on the membrane of
      hepatocytes. So, the liver imaging by GSA excludes the influence of the
      reticuloendothelial system. Therefore, the uptake of 99mTC-GSA is considered to
      be a useful method for the estimation of liver functional reserve in cases with
      obstructive jaundice. METHODOLOGY: In this study, we examined the uptake rate and
      specific binding capacities of 99mTC-GSA to receptors on the membrane of
      hepatocytes following 1, and 2 weeks of bile-duct ligation and 1 week after
      reduction of jaundice using the rat model. RESULTS: The hepatic uptake rate
      decreased as the period of jaundice was prolonged and returned to nearly normal
      by the reduction of jaundice. The value of specific binding capacities at 2 weeks
      after bile-duct ligation decreased significantly compared to the value of the
      control and the reduced group (P < 0.05). The cause of decrease in specific
      binding capacities was indicated as the decrease of affinity constant especially
      in the high affinity part. These results coincide with the change of binding
      capacities of insulin and glucagon receptors with obstructive jaundice, which
      accurately reflect the severity of hepatocyte injury. CONCLUSIONS: Taking
      together these results, 99mTC-GSA liver scintigraphy is thought to be a useful
      method to evaluate the liver functional reserve in cases with jaundice.

PMID- 11462924
TI  - Phase II study of systemic gemcitabine chemotherapy for advanced unresectable
      hepatobiliary carcinomas.
AB  - BACKGROUND/AIMS: Patients with advanced unresectable hepatobiliary carcinomas
      have a dismal prognosis. The efficacy of systemic chemotherapy in these patients
      is negligible and often, in particular in patients with hepatocellular
      carcinomas, the toxicity of chemotherapy outweighs the potential palliative
      effect of antineoplastic agents. Gemcitabine is a new anticancer agent with a
      mild toxicity profile, which has demonstrated antineoplastic activity in many
      solid tumors. Therefore we investigated the effect of gemcitabine in patients
      with advanced nonresectable hepatocellular and cholangiocellular carcinomas in a
      phase II study. METHODOLOGY: Twenty-three patients with cholangiocellular
      carcinoma and 20 patients with hepatocellular carcinoma were enrolled into the
      study. Eighteen of the 20 patients with hepatocellular carcinomas had liver
      cirrhosis. Gemcitabine was administered once weekly over 30 min for 3 consecutive
      weeks out of every 4 weeks. Patients with cholangiocellular carcinomas received
      gemcitabine also in the forth week of the first cycle with no rest to the
      following cycle. Disease status was assessed every 4 weeks. RESULTS: Overall the
      regimen was well tolerated. The median number of gemcitabine administration was
      15 (range, 3-37) in the group of patients with cholangiocellular carcinomas and
      7.6 (range, 3-21) in the group of patients with hepatocellular carcinomas. In the
      group of patients with hepatocellular carcinomas thrombocytopenia was the most
      frequent side effect (30% grade 3/4). Among the patients with cholangiocellular
      carcinomas nausea and neutropenia were the most commonly observed side effects.
      The overall response rate of hepatocellular carcinomas was only 5% and
      chemotherapy generally did not improve the tumor symptoms of the patients in this
      group. In contrast, in the group of cholangiocellular carcinomas, seven patients
      achieved a partial response (overall response rate 30%). Eleven patients with
      cholangiocellular carcinomas revealed tumor symptoms before the onset of
      gemcitabine treatment. Seven of these patients developed a treatment related
      clinical benefit as defined as a relief of tumor symptoms or gain of weight.
      CONCLUSIONS: Our results indicate that the treatment of cholangiocarcinomas with
      gemcitabine is effective and should be further evaluated in phase III studies. In
      contrast, palliative chemotherapy with gemcitabine cannot be recommended in
      patients with hepatocellular carcinoma and liver cirrhosis.

PMID- 11462925
TI  - Retrospective study on the effects of lipiodolization before a potentially
      curative hepatectomy for colorectal liver metastases: long-term results of a
      pilot study.
AB  - BACKGROUND/AIMS: Lipiodolization, a selective regional cancer chemotherapeutic
      modality using lipiodol plus anticancer drugs, can prolong the survival time of
      patients with unresectable liver cancer. A preliminary study was conducted with
      adjuvant lipiodolization before a potentially curative hepatectomy for patients
      with metachronous colorectal liver metastases. The ultimate aim of this study was
      to improve the long-term survival after hepatectomy. METHODOLOGY: Twenty-one
      consecutive patients with colorectal hepatic metastases were included in this
      study. Seven patients underwent preoperative lipiodolization, while the remaining
      14 patients did not receive any preoperative adjuvant therapy. The
      clinicopathological features and prognoses of these patients were investigated.
      The median follow-up period after a curative hepatectomy was 56 months. RESULTS:
      The clinicopathological factors did not differ markedly between the 2 groups.
      However, the cumulative survival rate of the 7 patients receiving preoperative
      lipiodolization was significantly (P < 0.05) better than that in those not
      receiving any preoperative treatment. CONCLUSIONS: Based on the above encouraging
      findings, we therefore propose that a prospective randomized trial should be
      carried out to confirm the beneficial effects of our adjuvant chemotherapeutic
      modality on patient survival following a curative hepatectomy for the patients
      with colorectal liver metastases.

PMID- 11462926
TI  - Salvaging procedures for dysfunctional peritoneovenous shunt.
AB  - BACKGROUND/AIMS: Peritoneovenous shunt is one of the treatments for refractory
      ascites. However, the dysfunction of the shunt is frequently seen and needs
      further management. We in this manuscript reported our experience in the
      salvaging procedures of dysfunctional peritoneovenous shunt. METHODOLOGY: A total
      of 29 Denver shunts were constructed for the management of refractory ascites at
      the Department of Surgery, National Taiwan University Hospital since January 1992
      to February 1999. A cross-sectional case study was performed. RESULTS: There was
      a total of 20 cases of mechanical dysfunction for these 29 patients. In the
      management of 6 peritoneal catheter occlusions which occurred in the early phase
      of this series, revision was performed by lengthening of the peritoneal catheter
      with a peritoneal dialysis catheter so that the catheter tip could rest in the
      Douglas pouch. The same procedure was adopted in the last 14 consecutive Denver
      shunts and this significantly decreased the incidence of peritoneal catheter
      occlusion (6/15 vs. 0/14, P = 0.011 by Fisher's exact test). In the 6 episodes of
      valve occlusion, the reservoir of the Denver shunt was replaced with a new one
      but the peritoneal and venous catheters were not changed. In the 8 episodes of
      venous catheter dysfunction, two venous catheters slipping out were managed by
      lengthening the catheter with a large-bore Hickmann catheter. In the other 6
      episodes, a new venous catheter was inserted to the other side of the internal
      jugular vein or saphenous vein through a subcutaneous tunnel and the catheter was
      connected to the reservoir with a connector. CONCLUSIONS: Although
      peritoneovenous shunt did not prolong the life expectancy of the patients with
      decompensated liver cirrhosis, it did relieve tense ascites rapidly and improve
      the quality of life remarkably. The modifications and salvaging procedures we
      used in our series could restore a dysfunctional Denver shunt easier, safer and
      with a higher cost-saving than a total revision of the shunt.

PMID- 11462927
TI  - The comparison of electron microscopy and scintigraphy in determining the
      protective effect of dimethylsulphoxide (DMSO) on ischemia/reperfusion injury
      through Pringle maneuver.
AB  - BACKGROUND/AIMS: We investigated the role of the electron microscopy and
      hepatobiliary scintigraphy in determining the effect of DMSO (dimethysulphoxide)
      and ischemia/reperfusion injury in the liver after the Pringle maneuver.
      METHODOLOGY: Twenty-four rabbits were divided into the following groups; A:
      Control group, B: Pringle, C: 10 mg/kg DMSO, D: 1 g/kg DMSO + Pringle. Group A
      was considered as a control group and only laparotomy was applied. Group B was
      exposed to Pringle maneuver only. Group C was given 10 mg/kg of DMSO via the vena
      cava inferior. Group D was given 1 g/kg of DMSO. A clamp was fastened for the
      groups of B, C and D in the 30th minute of the Pringle maneuver and a biopsy was
      applied five minutes later. Fifteen minutes later a dynamic hepatobiliary
      scintigraphy was applied. From dynamic images, liver peak time and activity half
      time of the liver were obtained. RESULTS: It was found that liver peak time and
      liver activity half time values of the group B, C and D were significantly longer
      than group A. Liver peak time and liver activity half time values of group B was
      not different from group C. However, some values of group D were found to be
      significantly shorter than groups B and C. In the electron microscopy
      examination, only in group B were some specific degenerative changes observed in
      the sinusoids. We observed less irreversible changes in group C than in group B.
      On the other hand, the least irreversible changes were in group D. CONCLUSIONS:
      As a conclusion, while electron microscopy is regarded as the "gold standard",
      hepatobiliary scintigraphy may be thought of as an easily applicable method in
      determining the ischemic reperfusion injury in the clinical comparison of the
      protective agents.

PMID- 11462928
TI  - Is hepatic resection for multiple liver metastases from colorectal carcinoma
      acceptable treatment?
AB  - BACKGROUND/AIMS: To determine an appropriate surgical treatment for patients with
      multiple liver metastases, we evaluated the efficacy of treatment in patients
      with 5 or more liver tumors in both lobes after metastasis from colorectal
      carcinoma which we refer to as H3 liver metastasis. METHODOLOGY: Seventy-two
      cases of H3 liver metastasis were classified as follows into four types according
      to tumor distribution in the liver: type A (n = 16), multiple metastases present
      in one lobe, and, in the other, confined to one segment; type B (n = 12),
      multiple metastases present bilaterally, but with tumors larger than 2 cm in
      diameter confined to one lobe or to three segments; type C (n = 10), multiple and
      diffuse metastases present in both lobes and all tumors 2 cm or less in diameter;
      and type D (n = 34) metastatic tumors larger than 2 cm in diameter occurring in
      every segment of the both lobes. Hepatectomy was performed within a possible
      range as a rule for all cases, and intrahepatic arterial infusion was performed
      in unresectable cases. In cases that responded to intrahepatic arterial infusion,
      hepatectomy was considered and performed when technically possible and
      potentially curative. RESULTS: The proportion of cases treated with hepatectomy
      were: type A, 56.3%; type B, 8.3%; type C, 10.0%; and type D, 2.9%. The regional
      intrahepatic arterial infusion ratios and response rates to it were 18.8% and
      0.0% in type A, 91.7% and 33.3% in type B, 80.0% and 71.4% in type C, and 64.7%
      and 0.0% in type D, respectively. One type B patient whose tumor showed complete
      resolution after intrahepatic arterial infusion and one type C patient with a
      partial response underwent hepatectomy. The cumulative survival rate at two years
      was significantly lower in type D (3.2%), than in the other types (type A, 33.3%;
      type B, 36.4%; and type C, 11.7%). CONCLUSIONS: These results suggested that
      hepatectomy should be performed in cases of type A, and that intrahepatic
      arterial infusion may be effective as neoadjuvant chemotherapy for type B or C.
      However, there is no effective treatment for type D at present.

PMID- 11462929
TI  - Complete resection of the caudate lobe of the liver with tumor: technique and
      experience.
AB  - BACKGROUND/AIMS: To study the technique and curative effects of complete
      resection of the caudate lobe of the liver with tumors. METHODOLOGY: There were
      18 patients with tumors in the caudate lobe of the liver in this study. Among
      them, hepatocellular carcinoma was found in 12 patients, metastasis to the
      caudate lobe two years after resection of rectal carcinoma in one,
      cholangiocarcinoma in one, and huge benign tumor in four. Complete caudate
      lobectomy and combined with left lateral lobectomy or left hemihepatectomy or
      left trilobectomy were performed in this series. RESULTS: The median operating
      time was 227 min and median blood loss was 1590 mL, and the median blood
      transfusion was 1520 mL. No operative or postoperative mortality, or any
      postoperative complications were found in any of the patients. The 1-, 3- and 5
      year survival rates of the 12 patients with hepatocellular carcinoma were 58.3%,
      55.5% and 37.8%, respectively. One patient with cholangiocarcinoma died in
      postoperative 4 months. One patient with metastatic rectal cancer has been alive
      for more than 5 years after the operation, and 4 patients with benign tumors are
      still alive and well. CONCLUSIONS: Complete resection of the caudate lobe of the
      liver should be the first choice for removal of huge tumors originating from the
      caudate lobe, although this procedure is quite difficult and has a high risk
      factor.

PMID- 11462930
TI  - Safety and utility of autologous blood transfusion for resection of metastatic
      liver tumor.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the safety and
      efficacy of predeposit autologous blood transfusion for resection of hepatic
      metastases. METHODOLOGY: We examined stored blood from 25 patients with advanced
      colorectal or gastric cancer for carcinoembryonic antigen mRNA using reverse
      transcriptase-polymerase chain reaction assay to detect cancer cell in the
      autologous blood. We also retrospectively evaluated no transfusion (A, n = 44),
      autologous transfusion (B, n = 15), and homologous transfusion groups (C, n = 26)
      for perioperative liver function and long-term outcome after undergoing resection
      of liver metastases. RESULTS: In 5 of 25 patients, carcinoembryonic antigen mRNA
      was detected immediately after blood donation and after 7 days of storage, but
      not after 14-21 days of storage. The cumulative 5-year survival rates for groups
      A, B, and C were not different. However, disease-free survival with colorectal
      liver metastases was significantly higher in group A than in group C (P = 0.019).
      Total bilirubin concentrations in group C on the first postoperative day were
      also significantly higher than group A (P = 0.025). CONCLUSIONS: Stored
      autologous blood may contain cancer cells, but these decrease or disappear after
      storage for more than 7 days. For hepatic resection of metastases, transfusion
      avoidance yields the optimal outcome.

PMID- 11462931
TI  - Activation of blood platelets in chronic hepatitis and liver cirrhosis P-selectin
      expression on blood platelets and secretory activity of beta-thromboglobulin and
      platelet factor-4.
AB  - BACKGROUND/AIMS: Blood platelets are cells that quite often undergo damage in
      chronic liver diseases. Endotoxemia and hyperkinetic circulation influence
      platelets in an active manner. The role of platelets in the development of
      hepatitis and liver fibrosis is speculative. The aim of the study was to
      determine the influence of chronic liver diseases on platelets morphologic
      parameters, their secretory activity and P-selectin expression. METHODOLOGY: The
      examination was completed in the group of 29 patients with chronic hepatitis and
      27 with liver cirrhosis of postinflammatory etiology (HBV, HCV). Liver biopsies
      were carried out in all patients. Thirty-two healthy individuals were the control
      group. Platelets morphological parameters (number, volume, platelet crit, micro-
      and macrothrombocyte fraction) were estimated. beta-thromboglobulin concentration
      and platelet factor 4 in blood serum as well as P-selectin expression on resting
      platelets and after thrombin activation were also examined. RESULTS: Number,
      volume, and platelet crit decreased with the advancement of a liver disease.
      Megathrombocyte fraction increased inversely with the severity of liver damage.
      The concentration of beta-thromboglobulin and platelet factor 4 alpha-granule
      contents in blood serum was higher 2- and 7-times, respectively than in healthy
      controls. P-selectin expression on resting platelets was considerably higher.
      After stimulation with thrombin, P-selectin expression was equal (chronic
      hepatitis) or higher (liver cirrhosis) than in the control. CONCLUSIONS: There
      are changes of platelet morphological parameters, with accompanying
      megathrombocyte fraction increase that occur in chronic liver diseases.
      Thrombocytes in chronic liver diseases and liver cirrhosis are more activated.
      Platelet sensitivity to stimuli in these ailments is higher (liver cirrhosis)
      than in the healthy controls.

PMID- 11462932
TI  - Child-Pugh class, nutritional indicators and early liver transplant outcomes.
AB  - BACKGROUND/AIMS: Patients with chronic liver disease undergoing liver
      transplantation have reduced body fat and muscle mass. The extent to which
      nutritional indicators and Child-Pugh class are predictive of postoperative
      outcome in adults is unclear. The aims of this study were to determine in adult
      patients undergoing transplant 1) the influence of preoperative Child-Pugh class
      and nutritional indicators on early transplant outcomes and one-year survival, 2)
      the relationship between nutritional indicators and Child-Pugh class and disease
      type. This study included 80 patients (1990-1994). METHODOLOGY: The nutritional
      indicators utilized were grip strength, triceps skinfold thickness and
      uncorrected mid-arm muscle area. Measured outcomes were ventilator time,
      intensive care stay, postoperative hospital stay and one-year survival. RESULTS:
      Early morbidity was determined in survivors. Child-Pugh class C patients required
      longer ventilation and spent more time in the intensive care unit than Child-Pugh
      classes A and B. No significant relationships were found for length of hospital
      stay. Relationships between the nutritional indicators (when controlled for Child
      Pugh class) and early morbidity could not be determined due to insufficient data.
      No relationship was established between one-year survival and Child-Pugh class or
      the nutritional indicators. Grip strength and mid-arm muscle area were lower in
      the patients in Child-Pugh classes B and C. Parenchymal liver disease was
      associated with lower grip strength and mid-arm muscle area when compared to
      cholestatic disease. CONCLUSIONS: Child-Pugh class C is associated with greater
      early postoperative morbidity. Advanced Child-Pugh class is also associated with
      diminished muscle status and parenchymal disease.

PMID- 11462933
TI  - Repeat hepatectomy for recurrent hepatic metastases from colorectal cancer.
AB  - BACKGROUND/AIMS: Resection of liver metastases from colorectal cancer is accepted
      as a safe, and curative treatment. Furthermore, repeat hepatectomy has been
      indicated for hepatic recurrence after initial hepatectomy to achieve long-term
      survival or cure. The present study is a retrospective review of our results
      using repeat hepatectomy for colorectal liver metastases to identify outcomes and
      prognostic factors associated with long-term survival. METHODOLOGY: Ninety-four
      patients underwent an initial hepatectomy for colorectal metastases between 1990
      and 1995. Thirty patients had hepatic recurrence after the initial hepatectomy.
      Eleven patients underwent repeat hepatectomy for isolated hepatic recurrence.
      RESULTS: The operative mortality was 0%. The overall 5-year survival rate after
      detection of second liver metastases of 11 patients was 45.5%. The distribution
      of first liver metastases and disease-free interval between the first and second
      hepatectomy demonstrated significance in relation to survival after repeat
      hepatectomy (P = 0.0303 and 0.0338). CONCLUSIONS: Repeat hepatectomy for
      recurrent liver metastases from colorectal cancer was the most effective
      treatment to improve survival time for selected patients. In patients with
      isolated second liver metastasis, unilateral spread of first liver metastases,
      and a disease-free interval between the first and second hepatectomies of more
      than 12 months, long-term survival or cure can be expected after repeat
      hepatectomy.

PMID- 11462934
TI  - Splenic arterial ligation prevents liver injury after a major hepatectomy by a
      reduction of surplus portal hypertension in hepatocellular carcinoma patients
      with cirrhosis.
AB  - BACKGROUND/AIMS: In this study, we investigated whether a reduction of surplus
      portal hypertension after a major hepatectomy by SPL (splenic arterial ligation)
      prevents a liver injury in cirrhotic patients with hepatocellular carcinoma.
      METHODOLOGY: Six hepatocellular carcinoma patients (SPL group) with liver
      cirrhosis (67 +/- 10 years old, ICGR15: 21.0 +/- 9.8%, T.Bil: 1.1 +/- 1.2 mg/dL)
      underwent major hepatectomy with splenic arterial ligation in order to reduce
      excessive portal hypertension after hepatectomy from 1998 to 2000, July. The
      patients (n = 15, 60 +/- 9 years old, ICGR15: 11.5 +/- 5.9%, T.Bil: 0.66 +/- 0.15
      mg/dL) who underwent liver resection above subsegmentectomy in the same period
      (control group) served as the control for SPL group. RESULTS: In the SPL group,
      the portal pressures before hepatectomy were 26 +/- 7 cm H2O and those after
      hepatectomy were 29 +/- 6 cm H2O. The portal pressure after splenic arterial
      ligation decreased to 24.5 +/- 6.3 cm H2O. The splenic tissue blood flows before
      SPL were 16.8 +/- 5.6 mL/min/100 g, while those after SPL were 7.2 +/- 2.2
      mL/min/100 g. The portal pressures before hepatectomy were 17 +/- 2 cm H2O and
      those after hepatectomy were 19 +/- 2 cm H2O in the six control patients. At the
      peak levels of liver function after surgery, T.Bil was 2.6 +/- 1.5 mg/dL, GOT was
      165 +/- 59 IU/L, and GPT was 107 +/- 49 IU/L. All patients could discharge
      without complications except for one case with bile leakage in SPL. At the peak
      levels of liver function in control group, T.Bil was 3.7 +/- 1.9 mg/dL, GOT was
      404 +/- 227 IU/L, and GPT was 322 +/- 171 IU/L. At the peak levels of liver
      function after surgery, T.Bil was 3.4 +/- 1.3 mg/dL, GOT was 398 +/- 289 IU/L,
      and GPT was 319 +/- 220 IU/L. Conversely, there were 11 episodes of complications
      (11/15), including two cases of hospital death resulting from liver failure in
      patients who underwent right lobectomy, in the control patients. CONCLUSIONS: The
      decompression of surplus portal hypertension by SPL might be effective in the
      prevention of post hepatectomized liver injury and the improvement of
      postoperative mortality and morbidity.

PMID- 11462935
TI  - Budd-Chiari syndrome secondary to intracardiac extension of hepatocellular
      carcinoma. Two cases treated by radical resection.
AB  - Two young women presenting Budd-Chiari syndrome as the primary manifestation of
      hepatocellular carcinoma with intracardiac extension were treated by debulking of
      the atrium and inferior vena cava under extracorporeal circulation and major
      hepatectomy. The first patient who was treated in a single procedure died during
      the immediate postoperative period. The second patient who was treated in two
      steps died of meningeal and pulmonary metastases 12 months later. Clinical
      findings and surgical strategy for this rare condition are discussed in the light
      of 6 previously reported surgical cases.

PMID- 11462936
TI  - Surgical closure of the gastrorenal shunt with distal splenorenal shunt operation
      for portosystemic encephalopathy.
AB  - A 67-year-old woman was admitted to our institution for hepatic encephalopathy.
      Careful examination revealed a large gastrorenal shunt. On an occlusion test of
      the gastrorenal shunt using a balloon catheter, portal vein pressure increased to
      as high as 26 cm H2O from the pretest value of 17.5 cm H2O. From the significant
      increase of portal vein pressure, it was thought that simple closure of the shunt
      could cause postoperative formation of an esophageal varix and its rupture. We
      thus performed shunt closure with distal splenorenal shunt with splenopancreatic
      and gastric disconnection to prevent the hazard. In treating the encephalopathy
      caused by a spontaneous shunt, it is one of the options to perform distal
      splenorenal shunt with splenopancreatic and gastric disconnection in addition to
      shunt closure if a remarkable increase of portal vein pressure is observed by the
      shunt occlusion test.

PMID- 11462937
TI  - Asymptomatic arterio-biliary fistula after transarterial chemoembolization of
      metastatic liver tumors.
AB  - Arterio-biliary fistula is a rare clinical condition resulting from various
      causes such as iatrogenic injury and ischemic change of the bile duct. Serious
      clinical symptoms occur due to the shunting of high-pressure blood from the
      hepatic artery into the bile duct. Here we report a case of arterio-biliary
      fistula demonstrated by angiographic examinations. The communication appeared
      after repeat transarterial chemoembolization of metastatic liver tumors. The
      interesting point of this case was that the patient did not have any obvious
      clinical symptoms related to the fistula. The mechanisms responsible for this
      rare manifestation are discussed.

PMID- 11462938
TI  - Application of liver transplantation for familial amyloid polyneuropathy combined
      with Crohn's disease.
AB  - We describe the case of a 31-year-old Japanese man with familial amyloid
      polyneuropathy combined with Crohn's disease, who underwent living-related
      orthotopic liver transplantation. Although he had a 2-year history of alternating
      constipation/diarrhea, his bowel symptoms exacerbated severely during the period
      he was in our ward for pretransplant evaluation. Small bowel barium examination
      and gastroduodenal endoscopy showed typical features of Crohn's disease. He was
      diagnosed as having active Crohn's disease, and the scheduled living-related
      orthotopic liver transplantation was postponed. After controlling the active
      disease with conservative therapy for two months, he underwent living-related
      orthotopic liver transplantation using a graft of the left lobe from his father.
      Postoperative medication consisted of azathioprine, aminosalicylates, tacrolimus
      and steroids. His postoperative course was uneventful, and he was discharged from
      hospital on the 25th postoperative day. Pre- and postoperative transplant
      management of patients with Crohn's disease is also discussed, because it
      influences the clinical course of inflammatory bowel diseases.

PMID- 11462939
TI  - Irrigation of liver abscess: proposal of a novel method and possible indications.
AB  - We present here two suggestive cases in considering the advantages and
      disadvantages of irrigation of pyogenic liver abscess: one patient developed an
      intrahepatic hematoma as an unusual sequela, while the other was successfully
      treated by abscess irrigation, overcoming failure of percutaneous catheter
      drainage and the patient's seriously ill condition. Based on these cases, we
      propose a novel method of liver abscess irrigation via percutaneous drainage
      tubes with the following three characteristics: 1) use of a drip infusion
      apparatus for irrigant instillation and drainage in order to avoid elevation of
      pressure in the abscess, a source of potential life-threatening sequelae, 2)
      addition of contrast medium to irrigant, and 3) employment of computed tomography
      in dynamic equilibrium of irrigant in order to evaluate the efficacy of current
      irrigation. Of interest was the parenchymal enhancement around the irrigated
      liver abscess revealed by computed tomography with this method, which suggested
      that dissemination of abscess contents may be inevitable with irrigation.
      Although the indications for liver abscess irrigation must be considered
      carefully given the critical sequelae potentially associated with it, the method
      we present can be used as a second-line trial exclusively for liver abscesses
      refractory to first-line treatment with percutaneous catheter drainage or needle
      aspiration, since it can be used not only as a therapeutic procedure with
      mechanical washing or dilution of abscess contents but also as a diagnostic aid
      enabling more effective subsequent treatment by defining the areas in which
      drainage and irrigation is not effective.

PMID- 11462940
TI  - Successful treatment for bronchial bleeding from invasive pulmonary metastasis of
      hepatocellular carcinoma: a case report.
AB  - Pulmonary metastasis is frequently seen in patients with advanced hepatocellular
      carcinoma. However, information is limited concerning life-threatening
      complications and effective treatment of pulmonary metastasis because of the poor
      prognosis of patients with advanced hepatocellular carcinoma. Recent remarkable
      progress in detection and treatment of hepatocellular carcinoma has improved
      prognosis, making management of pulmonary metastasis an important clinical issue.
      We describe a 68-year-old man with pulmonary metastasis of hepatocellular
      carcinoma and sudden onset of hemoptysis from bronchial invasion. Transcatheter
      embolization was performed successfully via the bronchial artery with
      disappearance of bloody sputum. Peribronchial pulmonary metastasis of
      hepatocellular carcinoma can cause life-threatening hemoptysis. Transcatheter
      arterial embolization may be one of therapeutics for hemoptysis from invasive
      pulmonary metastasis of hepatocellular carcinoma.

PMID- 11462941
TI  - Insulinoma: diagnostic strategies and surgical treatment. A 22-year experience.
AB  - BACKGROUND/AIMS: The efficacy of preoperative localization methods and the
      results of the surgical treatment of insulinoma were studied. METHODOLOGY: Fifty
      nine patients referred for surgical treatment were studied and the results of the
      diagnostic tools for tumor localization were compared with findings at surgical
      intervention. The influence of the type of surgical procedure in the immediate
      and late postoperative course was also studied. RESULTS: Ultrasonography had a
      sensitivity of 30%, computed tomography 25%, angiography 54%, portal vein
      sampling 94%, endoscopic ultrasonography 27% and magnetic resonance 17%.
      Intraoperative palpation localized 98.2% of the tumors and by the addition of
      intraoperative echography, all lesions were identified. In 55 patients with
      benign lesions, 22 enucleations, 25 distal pancreatectomies, 7 pancreatectomies
      plus enucleation and one duodenopancreatectomy were performed. Malignant tumors
      were treated by pancreatic resection, postoperative hepatic artery embolization
      and systemic chemotherapy. There was no postoperative mortality. Pancreatic
      fistula was the most common complication. Three patients who underwent distal
      pancreatectomy developed late diabetes (9.3%). CONCLUSIONS: Extensive
      preoperative investigation, mainly with invasive methods, is not indicated and by
      combining intraoperative palpation and echography most of the cases can be
      adequately dealt with. Preservation of pancreatic tissue with enucleation and
      preservation of the spleen are the best choice for treatment of benign
      insulinomas.

PMID- 11462942
TI  - Utility of serum CA 19-9 monitoring in preoperative radiotherapy for pancreatic
      cancer.
AB  - BACKGROUND/AIMS: Pancreatic cancer is extremely refractory even to aggressive
      treatments including surgery, resulting in early metastasis and/or local
      recurrence. We investigated changes in serum tumor marker CA 19-9 levels during
      preoperative radiotherapy in conjunction with initial treatment failure.
      METHODOLOGY: Twenty-three patients presenting with localized disease and an
      increased serum CA 19-9 level, who were slated to undergo pancreatectomy and/or
      intraoperative radiotherapy following preoperative radiotherapy were reviewed. CA
      19-9 response, the ratio of post-radiotherapy level before laparotomy to pre
      radiotherapy level, was analyzed in relation to disease-control time and
      survival. RESULTS: Eleven patients revealed metastasis at restaging or
      laparotomy; 12 patients (52%) completed aggressive treatments. Initial failure
      was identified at the liver (52%), peritoneum (52%), or local site (26%) with a
      median disease-control time of 91 days; 7 patients showed combined failure. All
      but 1 patient died of cancer with a median survival time of 264 days. CA 19-9
      response (range: 0-1185%) did not correlate with disease-control time or
      survival; 8 progressive-disease patients (> 140% response), however, showed
      significantly shorter disease-control time than 15 nonprogressive-disease
      patients (< or = 140% response). CONCLUSIONS: CA 19-9 monitoring is useful in
      preoperative radiotherapy for identifying patients who will not benefit by
      succeeding aggressive treatments by predicting early metastasis.

PMID- 11462943
TI  - Long-term results following different extent of resection in chronic
      pancreatitis.
AB  - BACKGROUND/AIMS: To evaluate, whether the indication related varying extent of
      resection in chronic pancreatitis has a predictable impact on long-term outcome.
      METHODOLOGY: One hundred and twenty-six patients consecutively underwent surgery
      for chronic pancreatitis from March 1987 to September 1997. Three treatment
      categories were defined: Pancreatoduodenectomy, duodenum-preserving resection and
      drainage procedures, and left-sided pancreatectomy. Main outcome measures were
      late mortality, pain scores preoperatively and at follow-up, body-weight change,
      percentage of insulin dependent diabetes, patient's and physician's satisfaction
      with surgery. RESULTS: Forty-one patients underwent pancreatoduodenectomy, 59
      drainage procedures, and 26 left-sided pancreatectomy, respectively. Hospital
      mortality was 1 (2.4%), 4 (6.8%), and 1 (3.8%) (P = NS), totaling 4.8%. After an
      average follow-up of 5.2 years, late mortality was 10 (24.4%), 9 (15.3%), and 4
      (15.4%) (P = NS) for a total of 23 (18.3%). Two patients (1.6%) died of
      unsuspected pancreatic cancer. Three patients (2.4%) had to be reoperated upon
      for pain relapse. The mean pain score was 8.8 preoperatively and 2.1 at late
      follow-up and not different among groups. Body-weight gain averaged 3.0, 4.0, and
      3.4 kg, with no significant differences. Percentage of insulin dependency in all
      patients rose from 14% prior to surgery to 30% at reevaluation, and was very
      similar in all treatment categories. CONCLUSIONS: The different kind and level of
      invasiveness of the surgical procedures did not significantly influence the late
      outcome. High rates of late mortality and deterioration of endocrine function are
      to a greater extent sequelae of comorbidity and the progression of the underlying
      pancreatic disease.

PMID- 11462944
TI  - Duodenal lesions following severe acute pancreatitis: review of 10 years'
      clinical experience.
AB  - BACKGROUND/AIMS: Acute pancreatitis may result in many local and contiguous organ
      complications; though the pancreas is in close proximity to the duodenum
      anatomically, acute pancreatitis causing duodenal lesions is rarely encountered.
      Our aim is to retrospectively evaluate the clinical features of the duodenal
      lesions in patients with severe acute pancreatitis. METHODOLOGY: During the past
      10 years, 1,637 consecutive patients with acute pancreatitis were admitted to
      Taipei Veterans General Hospital. Total parenteral nutrition was employed in 251
      patients with acute pancreatitis, defined as 'severe acute pancreatitis'. They
      had all received computed tomography during the hospitalization period, and the
      computed tomography reports were reviewed to find patients with duodenal
      involvement induced from pancreatitis. We defined those patients having duodenal
      wall thickening, extrinsic compression of the duodenum, or other obstructive
      lesions seen on the computed tomography scan as evident duodenal lesion or
      duodenal involvement. RESULTS: Nine cases of evident duodenal lesions following
      severe acute pancreatitis have been documented over a 10-year period in 1
      teaching medical center. The lesions were found by image study or during
      operation. The most frequently involved site was the second portion of the
      duodenum. Clinically, 1 unique case developed severe duodenal obstruction
      requiring surgical correction, and 7 cases recovered after supportive therapy. Of
      the 9, only 1 case died of multiple organ failure. CONCLUSIONS: In contrast to
      the colonic lesions caused by acute pancreatitis with a high morbidity and
      mortality, total parenteral nutrition yields a good prognosis in patients with
      evident duodenal lesions following severe acute pancreatitis.

PMID- 11462945
TI  - Analysis of postoperative pancreatitis in DSRS with SPD.
AB  - BACKGROUND/AIMS: Distal splenorenal shunt with splenopancreatic disconnection
      (DSRS + SPD) evolved to prevent the development of a pancreatic siphon, to
      improve maintenance as well as quality of portal perfusion and to achieve better
      long-term survival. We report several cases of postoperative pancreatitis in DSRS
      + SPD. Recently, oxygen-derived free radicals have been reported to play an
      important role in pathogenesis of acute pancreatitis. METHODOLOGY: In this study,
      ten cases of DSRS + SPD were examined intraoperatively. The local changes in
      oxygen-derived free radicals were obtained by measuring lipid peroxide and an
      endogenous scavenger (SOD) in the development of DSRS + SPD-induced pancreatitis.
      RESULTS: Lipid peroxide activity as the offense system was not changed before or
      after SPD. However, SOD activity as a defense system was significantly lowered
      after SPD compared to before SPD. CONCLUSIONS: These results indicate that an
      imbalance of both systems might be the cause of postoperative pancreatitis.

PMID- 11462946
TI  - Randomized trial of 5-fluorouracil, leucovorin and cisplatin in advanced
      pancreatic cancer.
AB  - BACKGROUND/AIMS: Phase II trials of combined 5 fluorouracil, leucovorin and
      cisplatin have demonstrated an 18-28% response rate in advanced pancreatic
      carcinomas. We investigated the effect of this chemotherapy regime on patients'
      survival. METHODOLOGY: Patients included gave informed consent. They had an
      advanced and proven pancreatic adenocarcinoma. The trial was multicentric,
      prospective and randomized. It compared a 5-day course of leucovorin (200
      mg/m2/day), 5-fluorouracil (375 mg/m2/day) and cisplatin (15 mg/m2/day) repeated
      every 21 days (23 patients) with a control group (22 patients). The main end
      points were survival time (Kaplan-Meier and log-rank methods) a[not readable: see
      text]side effects of chemotherapy. RESULTS: Association of leucovorin, 5
      fluorouracil and cisplatin failed to demonstrate any advantage of this regimen
      compared with supported care alone. Median survival times were 8.6 months (SD +/-
      1.8) and 7.0 months (SD +/- 0.6), respectively. The modulation of 5-fluorouracil
      by leucovorin and cisplatin was well tolerated with moderate toxic effects.
      CONCLUSIONS: This multicentric trial failed to demonstrate any advantage of the
      evaluated chemotherapy regime in the palliative treatment of cancer of the
      exocrine pancreas. Other trials including gemcitabine and/or radiotherapy are
      needed in advanced pancreatic adenocarcinoma.

PMID- 11462947
TI  - Immunohistochemical study of genetic alterations in intraductal and invasive
      ductal tumors of the pancreas.
AB  - BACKGROUND/AIMS: Multiple genetic alterations are involved in the development of
      pancreatic neoplasm. Here we investigated the incidence of p53, ras, bcl-2 and c
      erbB-2 gene alterations in intraductal papillary-mucinous tumors and invasive
      ductal adenocarcinoma of the pancreas by immunohistochemical method to identify
      and analyze their relationship in terms of these genetic alterations.
      METHODOLOGY: Fifty-four pancreatic lesions, including 18 benign (hyperplasia (3)
      and intraductal papillary adenoma (15)), and 16 malignant (carcinoma in situ (2)
      and intraductal papillary adenocarcinoma (14)) cases of intraductal papillary
      mucinous tumor; and 20 cases of invasive ductal adenocarcinoma, were
      immunostained by avidin-biotin peroxidase conjugate method. RESULTS: p53 and
      rasp21 expressions were significantly greater in malignant intraductal (P < 0.01,
      P < 0.05) and invasive ductal (P < 0.01, P < 0.01) tumors than in benign
      intraductal papillary-mucinous tumors; while bcl-2 and c-erbB-2 expressions were
      significantly greater in invasive ductal adenocarcinoma than both benign (P <
      0.01, P < 0.05) and malignant (P < 0.05, P < 0.05) intraductal papillary-mucinous
      tumors. CONCLUSIONS: Different groups of genetic alterations are involved in
      different phases of pancreatic tumorigenesis. p53 and ras gene alterations occur
      at an early stage during the development of intraductal papillary-mucinous tumor,
      while additional alterations of bcl-2 and c-erbB-2 occur during the development
      of invasive ductal adenocarcinoma of the pancreas.

PMID- 11462948
TI  - Portal vein resection in pancreatic head carcinoma. Part 1: Technical
      considerations.
AB  - It has been reported that pancreatic carcinoma invading the superior mesenterico
      portal vein confluence can be resected safely. Numerous techniques have been
      described for portal vein reconstruction, these procedures are described and
      discussed by the authors.

PMID- 11462949
TI  - Portal vein resection in pancreatic head carcinoma. Part 2: Clinical
      significance.
AB  - The prognosis of pancreatic carcinoma remains poor. Surgical resection provides
      the only chance for cure. Prognostic factors and survival are similar between
      patients who underwent portal vein resection compared with standard resection.
      Isolated portal vein involvement should not be a contraindication for pancreatic
      resection.

PMID- 11462950
TI  - Prognostic studies on gastric cancer with concomitant liver metastases.
AB  - BACKGROUND/AIMS: The aim of this study was to clarify prognostic factors after
      surgical treatments in gastric cancer patients having synchronous liver
      metastases. METHODOLOGY: Clinicopathological features and prognosis were
      retrospectively reviewed in 43 surgical patients with gastric cancer with
      concomitant liver metastases from 1984 to 1998. RESULTS: More than half of the
      patients (51.2%) had numerous liver metastases (H3). Rates of peritoneal
      metastases (P1, P2, P3: 34.9%), tumor serosal invasion (T3 or T4: 73.8%) and
      widespread lymph node metastases (N3, N4: 69.8%) were also high. Although the
      gastric resection was performed in 29 patients (67.5%), concomitant hepatectomy
      resection was performed in only 3 patients (7.0%). Univariate analysis revealed
      that the grade of liver metastases (H1, H2, H3) was only a statistically
      significant prognostic factor (P = 0.008). Concerning surgical treatments, the
      resection group had tendency to better survival than the nonresection group (P =
      0.074). Eight cases survived more than 1 year. Seven of the 8 cases (87.5%) were
      patients with gastrectomy. All of the 5 two-year survivors were patients with
      gastrectomy. CONCLUSIONS: In patients with gastric cancer with concomitant liver
      metastases, the grade of liver metastases indicate prognosis. In addition, there
      is possibility of palliative gastrectomy increasing the survival rare to more
      than one year.

PMID- 11462951
TI  - The value of D1 lymphadenectomy as prognostic marker in gastric cancer.
AB  - BACKGROUND/AIMS: To assess if the study on the involvement of perigastric lymph
      nodes, the only ones resected in D1 lymphadenectomy, is a valid prognostic marker
      in patients undergoing curative resection for gastric cancer. METHODOLOGY: A
      retrospective study was performed in 101 patients with gastric cancer, 34 women
      and 67 men, with a mean age of 61 years, undergoing curative resection by
      gastrectomy and D1 lymphadenectomy. Tumor size, the depth of tumoral invasion of
      the wall, nodal involvement and 5-year survival were assessed. RESULTS: Both
      tumor size and the depth of tumoral invasion of the wall were significantly
      related to metastatic involvement of perigastric lymph nodes. Similarly, tumoral
      involvement of the first-level lymph nodes was significantly associated with
      survival. CONCLUSIONS: D1 lymphadenectomy can provide adequate prognostic
      information in patients with gastric cancer undergoing curative resection.

PMID- 11462952
TI  - Acid-related diseases following retrosternal stomach interposition.
AB  - BACKGROUND/AIMS: Esophagectomy and reconstruction with retrosternal stomach
      interposition implies bilateral truncal vagotomy, which supposedly causes gastric
      functional impairment. METHODOLOGY: Esophagectomy and reconstruction with
      retrosternal stomach interposition was performed on 15 men (mean age: 58.4 years)
      and 3 women (mean age: 43.6 years). The stomach was pedicled on the right gastric
      and right gastroepiploic artery without performing pyloroplasty. The cervical
      side-to-end anastomosis was sutured manually. The functional results were
      assessed 2-4 years postoperatively, by determining 24-hour qualitative
      intragastric pH-measurement, fluoroscopical gastric emptying studies, fasting
      gastrin levels, and endoscopy with biopsy studies. RESULTS: Endoscopy and biopsy
      confirmed esophagitis in 12 patients, gastritis in 15 and a gastric ulcer in 1
      case. Fluoroscopic examination documented a normal passage of contrast medium in
      17, slight impairment in 1 case treated by balloon dilatation of the pylorus.
      Qualitative intragastric pH-measurement revealed a total pH < 3 in 22.5-98.05% of
      measuring events (mean: 74.31%) within 24 hours, in 18 cases. Only 4 patients had
      pH < 3 in less than 50%. Fasting gastrin levels (normal range: 25-110 mU/L)
      varied from 48.78 mU/L-168.20 (mean: 85.23 mU/L). Only 3 patients had levels >
      110 mU/L (maximum: 168.20 mU/L). CONCLUSIONS: Acid-related diseases may also
      occur after truncal vagotomy and retrosternal stomach interposition. Routine
      follow-up endoscopy and biopsy studies should be done to prevent inflammatory
      complications and maintain the patient's quality of life.

PMID- 11462953
TI  - A randomized clinical trial of pouch reconstruction after total gastrectomy for
      cancer: which is the better technique, Roux-en-Y or interposition?
AB  - BACKGROUND/AIMS: To determine the optimum pouch reconstruction after total
      gastrectomy, we conducted a randomized trial to compare the usefulness between PR
      and PI in terms of quality of life. METHODOLOGY: Thirty patients younger than 70
      years of age were selected and randomly classified into the following 2 groups:
      pouch and Roux-en-Y (PR; n = 15) and pouch and interposition (PI; n = 15). In
      each subject, the postoperative symptoms, food intake in a single meal, body
      weight, serum nutritional parameters, endoscopy, emptying time of the gastric
      substitute, and gallstone formation were evaluated. RESULTS: There were no
      significant differences in terms of the postprandial symptoms, food intake, body
      weight, and serum nutritional parameters until 2 years postoperative. Endoscopy
      showed a tendency of food stasis in the PR group, although this was not
      significant. The gastric emptying test in the PR group indicated that the
      retention capacity was slightly superior to that in the PI group. CONCLUSIONS:
      The impact of the duodenal passage on symptoms and nutrition could not be
      ascertained.

PMID- 11462954
TI  - Indications for pancreaticosplenectomy in advanced gastric cancer.
AB  - BACKGROUND/AIMS: The lymph nodes along the splenic artery (No. 11) and at the
      splenic hilum (No. 10) are classified in group 2 (n2) in the Japanese
      Classification of Gastric Carcinoma. Pancreaticosplenectomy is performed to
      achieve complete D2 dissection, but its efficacy remains controversial. To
      clarify the indications for pancreaticosplenectomy in gastric cancer, surgical
      results were investigated. METHODOLOGY: This study investigated 111 gastric
      cancer patients who underwent potentially curative total gastrectomy with
      pancreaticosplenectomy accompanied by D2 or more extensive lymph node dissection.
      The rate of lymph node metastasis and the number of Nos. 10 and 11 lymph nodes
      that contained metastases were ascertained from several histopathological
      findings. Predictive factors for metastasis in lymph nodes Nos. 10 and 11 and
      prognostic factors for survival were calculated and compared using the univariate
      and Cox proportional hazard regression model. RESULTS: Lymph node metastasis to
      No. 10 or 11 was observed in 19 patients. Of these, 8 (42.1%) had paraaortic
      lymph node metastases. The average number of metastatic lymph nodes in the 19
      patients was 19.4 +/- 19.2. The location of the primary tumor and the number of
      metastatic lymph nodes were correlated to lymph node metastasis to Nos. 10 and
      11. Of the regional lymph nodes, the right paracardial lymph nodes and those
      along the short gastric vessels frequently metastasized to No. 10 or 11. The 5
      year survival rate of patients with metastases in lymph nodes No. 10 or 11 was
      23.8% and that with No. 16 metastases was 24.5%, whereas that in n2 without
      metastasis in No. 10 or 11 was 41.4%. The independent prognostic factor was the
      number of metastatic lymph nodes. Of the postoperative complications, pancreatic
      fistula was observed in 43 patients (38.7%) and followed by anastomotic leakage
      in 6 (5.4%). CONCLUSIONS: Pancreaticosplenectomy is indicated in patients with
      advanced gastric cancer in the upper third or the whole of the stomach and with
      lymph node metastasis at right paracardial or along the short gastric vessels. To
      obtain good surgical results, pancreaticosplenectomy with paraaortic lymph node
      dissection (D3) should be carried out in patients with as few metastatic lymph
      nodes as possible.

PMID- 11462955
TI  - [Should abortion laws in France be relaxed again?].

PMID- 11462956
TI  - [Myoma and infertility: analysis of the literature].
AB  - The influence of myomas on reproduction has been clearly demonstrated, however
      their effects on fertility remain debated. The aim of this review, between
      January 1988 and December 2000, was to clarify the relation between myoma and
      fertility, and to assess pregnancy rates after myomectomy in infertile patients.
      Spontaneously, 54 publications were selected and 40 eligible. No study compared
      pregnancy rates with or without myomas. Pregnancy rates after myomectomy varied
      between 9.6% and 76.9%, with descriptive series. In medically assisted
      procreation, five publications were eligible. Myoma presence was associated with
      decreased pregnancy rates. Hysteroscopic sub-mucous myoma resection increased
      pregnancy rates. Relation between myoma and sterility is probable, however no
      proof was obtained. Myomectomy efficacy has not been statistically proven, but
      spontaneously almost 60% of patients became pregnant 24 months after surgery.
      Decreased pregnancy rates are observed when other infertility factors are
      associated. Concerning myomectomy in medically assisted procreation, conflicting
      results are available. Prospective randomised studies are needed.

PMID- 11462957
TI  - [Relationship between lymphatic metastasis in breast and cervix cancers and the
      level of CD44-H expression evaluated by an immunohistochemical method].
AB  - Immunohistochemistry has been used to evaluate the relationship between the rate
      of CD44-H antigen expression in breast invasive intracanalicuar and cervical
      epidermoid carcinomas and the presence of node metastasis. A total of 36 cases of
      breast carcinoma and 20 cases of cervical carcinoma was examined. For the two
      types of carcinoma, the CD44-H molecule was highly expressed in cases with node
      metastasis; with 50% and 75% median value of CD44-H positive tumor cells
      respectively for the breast (p < 0.02) and for the uterine cervix (p < 0.05)
      compared to respectively 10% and 37.5% in the cases without node metastasis. The
      expression of this molecule increases with invasive potential of tumor cells and
      the use of this antigen for prognostic ends may be possible.

PMID- 11462958
TI  - [Value of ureteral catheterization in laparoscopy].
AB  - OBJECTIVE: Describe indications and procedures of ureteral retrograde catheter
      placement in operative laparoscopy. Assess the security that allows this
      technique to avoid or detect ureteral injury. STUDY DESIGN: A cohort study over a
      five year period was performed on 1722 patients who underwent an operative
      gynecologic laparoscopy. SURGICAL TECHNIQUE: When presumptive evidence of ureter
      adhesiolysis (dense adhesions from previous surgery, endometriosis), or suspicion
      of iatrogenic ureter transection, laparoscopic procedure was interrupted. A
      cystoscopy was performed and an internalized stent was inserted. RESULTS: In nine
      cases (preventive indications), patients required this procedure in adnexal
      surgery (dense adhesions from previous operations endometriosis), in oophorectomy
      for residual ovary syndrome and ovarian remnant syndrome and in hysterectomy with
      an intraligamentary leiomyomata. In one case (diagnostic indication), ureteral
      catheter placement was performed after use of an endoscopic linear stapler during
      a laparoscopically assisted vaginal hysterectomy. CONCLUSION: This intra
      operative procedure can allow better ureter recognition and its safe dissection
      when complex operative laparoscopy is foreseen.

PMID- 11462959
TI  - [Neonatal bacterial infections at the CUH of Dakar].
AB  - OBJECTIVES: It's a retrospective study in order to determine the epidemiology of
      neonatal bacterial infection and to evaluate the efficiency of the antibiotic
      protocol in University Teaching Hospital in Dakar. MATERIAL AND METHODES: From
      January 1st 1997 to December 31st 1998 we have registered 7461 live births,
      samples of blood are taken from 2312 new-born baby and they received
      antibiotherapy (beta-lactamine + gentamycin) at the first day based on infections
      risk evaluated by anamnestic criterias. The treatment is seven to one days long,
      the antibiotic was adapted according to the antibiogram result. RESULTS: The
      neonatal infection diagnosis is confirmed in 246 cases, about 33 per 1000 live
      births or 10.6% of newborn babies having on antibiotherapy. Most current risk
      factors are premature rupture of membranes (85%) and neonatal suffering (87.8%).
      Isolated gerras are: Klebsiella pneumoniae (61.5%), Enterobacteria (11.5
      Staphylococcus (8.7%), colibacille (6%), Streptococcus (5.5%), Enterococcus
      (4.1%) and Pseudomonas (2.7%). Most of these germs are resistant to antibiotics
      currently used in first intention (ampicillin, cefotaxim, gentamycin), in
      particularly 95% of Klebsiella. Most efficient antibiotics are amikacin,
      colistin, ceftriaxon and ciprofloxacine. Deaths occurs in 48 cases with 36 in
      early neonatal period, 79% of mortality rate related to infection by Klebsiella.
      CONCLUSION: First intention antibiotherapy must be always adapted to the
      bacterial ecology evolution and must be more selective by using major infections
      risk factors. We promote early infection diagnosis by using biologic markers
      which reference is represented by C Reactive Protein.

PMID- 11462960
TI  - [Maternal anxiety induced by prenatal diagnostic techniques: detection and
      management].
AB  - Recent improvement in the screening for chromosomal defects, in particular the
      widespread use of ultrasonography and maternal biochemistry, is leading to a high
      number of fetal invasive tests (amniocentesis or chorion villus sampling). An
      increased level of anxiety in the pregnant women, which may sometimes continue
      until the postnatal period, is believed to be due to these prenatal diagnosis
      procedures. Maternal anxiety originates in the doubts related to fetal integrity
      and pregnancy outcome after information of a positive biochemical screening or
      visualisation of an ultrasound marker of chromosomal abnormality. Each specialist
      involved in prenatal care should take special attention to this, because of at
      least two reasons. First, anxiety may reduce maternal well being during
      pregnancy. Second, because it could have deleterious effects on parent to infant
      relationships. Without any intention of lowering the positive aspects of prenatal
      diagnosis, it appears essential to consider the negative effects anxiety may have
      on both parents. From our own experience and the conclusion of previous reported
      studies, we suggest some measures to reduce the level of maternal anxiety related
      to prenatal diagnosis: (i) improvement in the quality and transparency of
      information offered to pregnant women; (ii) training and involvement in
      psychological and emotional care for each member in the medical team; (iii)
      special and systematic psychological care for the "high risk" pregnant women
      regarding anxious disorders.

PMID- 11462961
TI  - [Endometrial adenofibroma].
AB  - We report a case of papillary adenofibroma of the uterine corpus in a 31 year-old
      woman who was initially examined for vaginal bleeding. Pelvic examination showed
      a large polypoid mass protruding through the cervix canal. A pelvic ultrasound
      revealed a polypoid cystic mass apparently arising from the uterus. A polypectomy
      was performed. The tumor was composed histologically by begin epithelial and
      mesenchymal components. Uterine adenofibroma is a extremely rare tumor which
      considered to be a mixed tumor of Mullerian origin. This lesion appears to be
      clinically and histologically benign but must be differentiated from other
      malignant lesions of the uterus, particularly from the adenosarcoma.

PMID- 11462962
TI  - [Reply from the authers to the letter from C. Bergeron].

PMID- 11462963
TI  - [In reply to the article by J. Choper et al. Non-palpable breast lesions:
      radiopathological correlations on surgical excision samples. Importance of the
      choice of minimal excisional technique. Gynecol Obstet Fertil 2000; 28: 888-95].

PMID- 11462964
TI  - [In reply to the article by S. Mimoun et al. Apropos of menstruation and its
      disorders in 603 women using contraception in 1999. Gynecol Obstet Fertil 2001;
      29: 904-12].

PMID- 11462965
TI  - [Dyspareunia of menopausal women (psychological and sexological aspects)].

PMID- 11462966
TI  - [Fertiloscopy].

PMID- 11462967
TI  - [Hydrosalpinx and fertilization in vitro-embryo transfer: abstention or
      salpingectomy? Abstention, salpingectomy or salpingostomy?].

PMID- 11462968
TI  - [[Hydrosalpinx and fertilization in vitro-embryo transfer: abstention or
      salpingectomy? Salpingectomy, yes but when and for whom?].

PMID- 11462969
TI  - New dermatological agents for the treatment of psoriasis.

PMID- 11462970
TI  - Design of remarkably simple, yet potent urea-based inhibitors of glutamate
      carboxypeptidase II (NAALADase).

PMID- 11462971
TI  - [3H]N-2-(4-(N-benzamido)phenyl)propyl-2-propanesulfonamide: a novel AMPA receptor
      potentiator and radioligand.

PMID- 11462972
TI  - Quinoxalinylethylpyridylthioureas (QXPTs) as potent non-nucleoside HIV-1 reverse
      transcriptase (RT) inhibitors. Further SAR studies and identification of a novel
      orally bioavailable hydrazine-based antiviral agent.
AB  - Quinoxalinylethylpyridylthioureas (QXPTs) represent a new class of human
      immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase (RT)
      inhibitors (NNRTIs) whose prototype is 6-FQXPT (6). Docking studies based on the
      three-dimensional structure of RT prompted the synthesis of novel
      heteroarylethylpyridylthioureas which were tested as anti-HIV agents. Several
      compounds proved to be potent broad-spectrum enzyme inhibitors and significantly
      inhibited HIV-1 replication in vitro. Their potency depends on the substituents
      and the nature of the heterocyclic skeleton linked to the ethyl spacer, and
      structure-activity relationships are discussed in terms of the possible
      interaction with the RT binding site. Although the new QXPTs analogues show
      potent antiviral activity, none of the compounds tested overcome the
      pharmacokinetic disadvantages inherent to ethylpyridylthioureidic antiviral
      agents, which in general have very low oral bioavailability. Through an
      integrated effort involving synthesis, docking studies, and biological and
      pharmacokinetic evaluation, we investigated the structural dependence of the poor
      bioavailability and rapid clearance within the thioureidic series of antivirals.
      Replacing the ethylthioureidic moiety with a hydrazine linker led to a new
      antiviral lead, offering promising pharmacological and pharmacokinetic properties
      in terms of antiviral activity and oral bioavailability.

PMID- 11462973
TI  - 3-Aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones: a new class of selective A1
      adenosine receptor antagonists.
AB  - Radioligand binding assays using bovine cortical membrane preparations and
      biochemical in vitro studies revealed that various 3-aryl[1,2,4]triazino[4,3
      a]benzimidazol-4(10H)-one (ATBI) derivatives, previously reported by us as
      ligands of the central benzodiazepine receptor (BzR) (Primofiore, G.; et al. J.
      Med. Chem. 2000, 43, 96-102), behaved as antagonists at the A1 adenosine receptor
      (A1AR). Alkylation of the nitrogen at position 10 of the triazinobenzimidazole
      nucleus conferred selectivity for the A1AR vs the BzR. The most potent ligand of
      the ATBI series (10-methyl-3-phenyl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one
      12) displayed a Ki value of 63 nM at the A1AR without binding appreciably to the
      adenosine A2A and A3 nor to the benzodiazepine receptor. Pharmacophore-based
      modeling studies in which 12 was compared against a set of well-established A1AR
      antagonists suggested that three hydrogen bonding sites (HB1 acceptor, HB2 and
      HB3 donors) and three lipophilic pockets (L1, L2, and L3) might be available to
      antagonists within the A1AR binding cleft. According to the proposed
      pharmacophore scheme, the lead compound 12 engages interactions with the HB2 site
      (via the N2 nitrogen) as well as with the L2 and L3 sites (through the pendant
      and the fused benzene rings). The results of these studies prompted the
      replacement of the methyl with more lipophilic groups at the 10-position (to fill
      the putative L1 lipophilic pocket) as a strategy to improve A1AR affinity. Among
      the new compounds synthesized and tested, the 3,10-diphenyl[1,2,4]triazino[4,3
      a]benzimidazol-4(10H)-one (23) was characterized by a Ki value of 18 nM which
      represents a 3.5-fold gain of A1AR affinity compared with the lead 12. A
      rhodopsin-based model of the bovine adenosine A1AR was built to highlight the
      binding mode of 23 and two well-known A1AR antagonists (III and VII) and to guide
      future lead optimization projects. In our docking simulations, 23 receives a
      hydrogen bond (via the N1 nitrogen) from the side chain of Asn247 (corresponding
      to the HB1 and HB2 sites) and fills the L1, L2, and L3 lipophilic pockets with
      the 10-phenyl, 3-phenyl, and fused benzene rings, respectively.

PMID- 11462974
TI  - Design, synthesis, and modeling of novel cyclic thrombin receptor-derived peptide
      analogues of the Ser42-Phe-Leu-Leu-Arg46 motif sequence with fixed conformations
      of pharmacophoric groups: importance of a Phe/Arg/NH2 cluster for receptor
      activation and implications in the design of nonpeptide thrombin receptor
      mimetics.
AB  - The novel cyclic analogues cyclo(Phe-Leu-Leu-Arg-epsilonLys-Dap) (1) and cyclo(D
      Phe-Leu-Leu-Arg-epsilonLys-Dap) (2), which differ only in the absolute
      conformation of Phe, have been designed and synthesized based upon the minimal
      peptide sequence Phe-Leu-Leu-Arg which has been found to exhibit biological
      activity for the thrombin receptor. Compound 1, in which all amino acids have the
      L-configuration, exhibited higher activity in the rat aorta relaxation and rat
      longitudinal muscle bioassays compared to compound 2, in which the Phe residue is
      in the D-configuration. This is attributed to the spatial proximity of the Phe
      and Arg in compound 1 which does not exist in its diastereomeric compound 2, as
      is depicted from a combination of NMR studies and computational analysis.
      Structure-activity studies (SAR) showed that the Phe and Arg side chains along
      with a primary amino group form an active recognition motif that is augmented by
      the presence of a second primary amino group in the cyclic peptide. We suggest
      that a comparable cyclic conformation may be responsible for the interaction of
      linear TRAPs with the thrombin receptor. The validity of this proposition was
      tested by the synthesis of four active nonpeptide thrombin receptor mimetics.
      Substance (S)-N-(6-guanidohexanoyl)-N'-(2-amino-3-phenylpropionyl)piperazine (3),
      in which the pharmacophoric phenyl, guanidino, and amino groups were incorporated
      onto a piperazine template, was found to be the most active compared to the other
      synthesized compounds which lack the amino pharmacophoric group.

PMID- 11462975
TI  - Structure-activity relationships of pyridoxal phosphate derivatives as potent and
      selective antagonists of P2X1 receptors.
AB  - Novel analogues of the P2 receptor antagonist pyridoxal-5'-phosphate 6-azophenyl
      2',5'-disulfonate (2) were synthesized and studied as antagonists in functional
      assays at recombinant rat P2X1, P2X2, and P2X3 receptors expressed in Xenopus
      oocytes (ion flux stimulation) and at turkey erythrocyte P2Y1 receptors
      (phospholipase C activation). Selected compounds were also evaluated as
      antagonists of ion flux and the opening of a large pore at the recombinant human
      P2X7 receptor. Modifications were made in the 4-aldehyde and 5'-phosphate groups
      of the pyridoxal moiety: i.e. a CH2OH group at the 4-position in pyridoxine was
      either condensed as a cyclic phosphate or phosphorylated separately to form a
      bisphosphate, which reduced potency at P2 receptors. 5-Methylphosphonate
      substitution, anticipated to increase stability to hydrolysis, preserved P2
      receptor potency. At the 6-position, halo, carboxylate, sulfonate, and
      phosphonate variations made on the phenylazo ring modulated potency at P2
      receptors. The p-carboxyphenylazo analogue, 4, of phosphate 2 displayed an IC50
      value of 9 nM at recombinant P2X1 receptors and was 1300-, 16-, and > 10,000-fold
      selective for P2X1 versus P2X2, P2X3, and P2Y1 subtypes, respectively. The
      corresponding 5-methylphosphonate was equipotent at P2X1 receptors. The 5
      methylphosphonate analogue containing a 6-[3,5-bis(methylphosphonate)]phenylazo
      moiety, 9, had IC50 values of 11 and 25 nM at recombinant P2X1 and P2X3
      receptors, respectively. The analogue containing a phenylazo 4-phosphonate group,
      11, was also very potent at both P2X1 and P2X3 receptors. However, the
      corresponding 2,5-disulfonate analogue, 10, was 28-fold selective for P2X1 versus
      P2X3 receptors. None of the analogues were more potent at P2X7 and P2Y1 receptors
      than 2, which acted in the micromolar range at these two subtypes.

PMID- 11462976
TI  - Synthesis and SAR of a new series of COX-2-selective inhibitors: pyrazolo[1,5
      a]pyrimidines.
AB  - The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5
      a]pyrimidines as potent and selective cyclooxygenase-2 (COX-2) inhibitors are
      described. The new compounds were evaluated both in vitro (COX-1 and COX-2
      inhibition in human whole blood) and in vivo (carrageenan-induced paw edema and
      air-pouch model). Modification of the pyrimidine substituents showed that 6,7
      disubstitution provided the best activity and led to the identification of 3-(4
      fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidine
      (10f) as one of the most potent and selective COX-2 inhibitor in this series.

PMID- 11462977
TI  - Analogues of prazosin that bear a benextramine-related polyamine backbone exhibit
      different antagonism toward alpha1-adrenoreceptor subtypes.
AB  - Hybrid tetraaamine disulfides 4-9 were synthesized by combining the structural
      features of prazosin (1), a competitive alpha1-adrenoreceptor antagonist, and
      benextramine (2), an irreversible alpha1/alpha2-adrenoreceptor antagonist, and
      their biological profiles at alpha1-adrenoreceptor subtypes were assessed by
      functional experiments in isolated rat vas deferens (alpha1A), spleen (alpha1B),
      and aorta (alpha1D). To verify the role of the disulfide moiety on the
      interaction with alpha1-adrenoreceptor subtypes, carbon analogues 10-15 were
      included in this study. All quinazolines lacking the disulfide bridge behaved,
      like 1, as competitive antagonists, whereas all polyamine disulfides displayed a
      nonhomogeneous mechanism of inhibition at the three subtypes since they were,
      like 2, noncompetitive antagonists at the alpha1A and alpha1B subtypes while
      being, unlike 2, competitive antagonists at the alpha1D. In particular, the
      blocking effects were characterized by a decrease of the maximal response to
      noradrenaline that was affected only slightly by washings. Probably the alpha1A
      and alpha1B subtypes bear in the binding pocket a suitable thiol function that
      would suffer an interchange reaction with the disulfide moiety of the antagonist
      and which is missing, or not accessible, in the alpha1D subtype. Polyamines 8, 9,
      and 14, among others, emerged as promising tools for the characterization of
      alpha1-adrenoreceptors, owing to their receptor subtype selectivity. Finally, the
      effect of nonbasic substituents on the phenyl ring of prazosin analogues 16-28 on
      potency and selectivity for the different subtypes can hardly be rationalized.

PMID- 11462978
TI  - Behavioral approach to nondyskinetic dopamine antagonists: identification of
      seroquel.
AB  - A great need exists for antipsychotic drugs which will not induce extrapyramidal
      symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be
      a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine
      D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor
      antagonist which appears to act selectively in the mesolimbic area. In this work
      dopamine antagonism was assessed in two mouse behavioral assays: antagonism of
      apomorphine-induced climbing and antagonism of apomorphine-induced disruption of
      swimming. The potential for the liability of dyskinesias was determined in
      haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners
      of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic
      potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was
      dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias whereas its N-2
      (2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such
      distinctions presented an opportunity. Thus, aromatic and N-substituted analogues
      of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1
      yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11
      (4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was
      found to be an apomorphine antagonist comparable to clozapine. It was essentially
      nondyskinetic in the Cebus model. With 23 as a platform, a number of N
      substituted analogues were found to be good apomorphine antagonists but all were
      dyskinetic.

PMID- 11462979
TI  - Conformationally restricted analogues of 1N,14N-bisethylhomospermine (BE-4-4-4):
      synthesis and growth inhibitory effects on human prostate cancer cells.
AB  - Twelve analogues of 1N,14N-bisethylhomospermine (BE-4-4-4) with restricted
      conformations were synthesized in the search for cancer chemotherapeutic agents
      with higher cytotoxic activities and lower systemic toxicities than BE-4-4-4. The
      central butane segment of BE-4-4-4 was replaced with a 1,2-substituted
      cyclopropane ring, a 1,2-substituted cyclobutane ring, and a 2-butene residue. In
      each case, the cis/trans-isomeric pair was synthesized. Cis-monounsaturation(s)
      was also introduced at the outer butane segment(s) of BE-4-4-4. The two possible
      cis-dienes and a cis-triene formally derived from the tetraazaeicosane skeleton
      of BE-4-4-4 were also prepared. Four cultured human prostate cancer cell lines
      (LnCap, DU145, DuPro, and PC-3) were treated with the new tetramines to examine
      their effects on cell growth with a MTT assay. One representative cell line
      (DuPro) was selected to further study the cellular uptake of the novel
      tetramines, their effects on intracellular polyamine pools, and their
      cytotoxicity. All tetramines entered the cells, reduced cellular putrescine and
      spermidine pools while exerting only a small effect on the spermine pool,
      inhibited cell growth, and killed 2-3 logs of cells after 6 days of treatment at
      10 microM. Four new tetramines, the two cyclopropyl isomers, the trans-cyclobutyl
      isomer, and the (5Z)-tetraazaeicosene, were more cytotoxic than their saturated
      counterpart (BE-4-4-4). Their cytotoxicity, however, could not be correlated
      either with their cellular uptake or with their ability to deplete intracellular
      polyamine pools. We attribute their cytotoxicity to their specific molecular
      structures. The cytotoxicity was markedly reduced when the central butane segment
      was deprived of its rotational freedom by replacing it with a double bond.
      Introduction of a triple bond or a benzene-1,2-dimethyl residue at the central
      segment of the polyamine chain, led to complete loss of biological activity. The
      conformationally restricted alicyclic derivatives were not only more cytotoxic
      than was the freely rotating BE-4-4-4 by several orders of magnitude but also had
      much lower systemic toxicities than the latter. Thus, we obtained new tetramines
      with a wider therapeutic window than BE-4-4-4.

PMID- 11462980
TI  - cis-Unsaturated analogues of 3,8,13,18,23-pentaazapentacosane (BE-4-4-4-4):
      synthesis and growth inhibitory effects on human prostate cancer cell lines.
AB  - From the results of our previous physicochemical studies of polyamine-nucleic
      acid interactions, we concluded that polyamine analogues in cisoidal conformation
      are capable of wrapping around the major groove of the double helix, of
      displacing natural polyamines from their nucleic acid binding sites, and of
      inhibiting cell division. On the basis of this hypothesis, nine unsaturated
      pentamines, formally derived from the cytotoxic pentamine 3,8,13,18,23
      pentaazapentacosane (BE-4-4-4-4), were prepared in an attempt to increase
      antineoplastic activity. Cis-double bonds were introduced in all possible sites
      in the saturated pentaazapentacosane structure of BE-4-4-4-4 to yield two
      pentacosenes, four pentacosadienes, two pentacosatrienes, and one
      pentacosatetraene. Cis-double bonds should also provide good targets for mixed
      function oxidases that might eliminate the accumulation of unsaturated pentamines
      in serum, thereby reducing systemic toxicity in animals. We determined the
      ability of these new pentamines to inhibit growth in four cultured human prostate
      cancer cell lines (LnCap, DU145, PC-3, and DuPro) using a MTT assay. LnCap and
      DU145 cells were very sensitive, PC-3 cells were relatively resistant, and DuPro
      cells were intermediate in sensitivity to most of these synthetic pentamines. In
      all cell lines, pentamines that had unsaturation(s) at the end of the chain
      showed the highest cell growth inhibitory effects. The cellular uptake, effects
      on cellular polyamine levels, and cytotoxicity of these pentamines on one
      representative prostate cancer cell line (DuPro) were further examined with a
      colony-forming efficiency (CFE) assay. The pentamines with unsaturation(s) at the
      end of the chain were once again the most cytotoxic among both the saturated (BE
      4-4-4-4) and unsaturated analogues. Appreciable amounts of all pentamines entered
      DuPro cells and depleted cellular polyamine pools by day 6 of treatment. For most
      pentamines, however, cell growth inhibitory and cytotoxic effects could not be
      directly correlated either with their cellular uptake or with their ability to
      deplete cellular polyamine pools. The position of the double bonds in the
      aliphatic backbone seems to be the most important determinant of cytotoxicity.
      For some pentamines, however, depletion of cellular polyamines may add to their
      efficacy.

PMID- 11462981
TI  - New 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives, with dual action at 5
      HT1A serotonin receptors and serotonin transporter, as a new class of
      antidepressants.
AB  - In a search toward new and efficient antidepressants, 1-aryl-3-(4-arylpiperazin-1
      yl)propane derivatives were designed, synthesized, and evaluated for 5-HT
      reuptake inhibition and 5-HT1A receptor antagonism. This dual pharmacological
      profile should lead, in principle, to a rapid and pronounced enhancement in
      serotoninergic neurotransmission and consequently to a more efficacious treatment
      of depression. The design was based on coupling structural moieties related to
      inhibition of serotonin reuptake, such as gamma-phenoxypropylamines, to
      arylpiperazines, typical 5-HT1A ligands. In binding studies, several compounds
      showed affinity at the 5-HT transporter and 5-HT1A receptors. Antidepressant-like
      activity was initially assayed in the forced swimming test with those compounds
      with Ki < 200 nM in both binding studies. Functional characterization was
      performed by measuring the intrinsic effect on rectal temperature in mice and
      also the antagonism to 8-OH-DPAT-induced hypothermia. The most efficacious
      compounds (12f, 23gE, 28a, and 28b) were further explored for their ability to
      antagonize 8-OH-DPAT-induced inhibition of forskolin-stimulated cAMP formation in
      a cell line expressing the 5-HT1A receptor. Furthermore, the antidepressant-like
      properties of 12f, 28a, and 28b, which exhibited 5-HT1A receptor antagonistic
      property in the latter study, were also evaluated in the learned helplessness
      test in rats. Among these three compounds, 28b (1-benzo[b]thiophene-3-yl)-3-[4-(2
      methoxyphenyl)-1-ylpropan-1-ol) showed the higher affinity at both the 5-HT
      transporter and 5-HT1A receptors (Ki = 20 nM in both cases) and was also active
      in the other pharmacological tests. Such a pharmacological profile could lead to
      a new class of antidepressants with a dual mechanism of action and a faster onset
      of action.

PMID- 11462982
TI  - Tyrosine kinase inhibitors. 18. 6-Substituted 4-anilinoquinazolines and 4
      anilinopyrido[3,4-d]pyrimidines as soluble, irreversible inhibitors of the
      epidermal growth factor receptor.
AB  - 4-Anilinoquinazoline- and 4-anilinopyrido[3,4-d]pyrimidine-6-acrylamides are
      potent pan-erbB tyrosine kinase inactivators, and one example (CI-1033) is in
      clinical trial. A series of analogues with a variety of Michael acceptor units at
      the 6-position were prepared to define the structural requirements for
      irreversible inhibition. A particular goal was to determine whether additional
      functions to increase solubility could be appended to the Michael acceptor.
      Substituted acrylamides were prepared by direct acylation of the corresponding 6
      amines with the requisite acid or acid chloride. Vinylsulfonamide derivatives
      were obtained by acylation of the amines with chloroethylsulfonyl chloride
      followed by base-promoted elimination. Vinylsulfone and vinylsulfine derivatives
      were prepared by oxidation and base elimination of a hydroxyethylthio
      intermediate. The compounds were evaluated for their inhibition of
      phosphorylation of the isolated EGFR enzyme and for inhibition of EGF-stimulated
      autophosphorylation of EGFR in A431 cells and of heregulin-stimulated
      autophosphorylation of erbB2 in MDA-MB 453 cells. Substitution at the nitrogen of
      the acrylamide was tolerated only with a methyl group; larger substituents were
      dystherapeutic, and no substitution at all was tolerated at the acrylamide alpha
      carbon. In contrast, while electron-donating groups at the acrylamide beta-carbon
      were not useful, even quite large electron-withdrawing groups (which increase its
      electrophilicity) were tolerated. A series of derivatives with solubility
      enhancing substituents linked to the acrylamide beta-carbon via amides were
      potent irreversible inhibitors of isolated EGFR (IC50s = 0.4-1.1 nM), with weakly
      basic morpholine and imidazole derivatives being the best. Vinylsulfonamides were
      also potent and irreversible inhibitors, but vinylsulfones and vinylsulfines were
      reversible and only poorly active. Two compounds were evaluated against A431,
      H125, and MCF-7 xenografts in nude mice but were inferior in these assays to the
      clinical trial compound CI-1033.

PMID- 11462983
TI  - Design, synthesis, and biological evaluation of a series of lavendustin A
      analogues that inhibit EGFR and Syk tyrosine kinases, as well as tubulin
      polymerization.
AB  - A series of N-alkylamide analogues of the lavendustin A pharmacophore were
      synthesized and tested for inhibition of the epidermal growth factor receptor
      (EGFR) protein tyrosine kinase and the nonreceptor protein tyrosine kinase Syk.
      Although several compounds in the series were effective inhibitors of both
      kinases, it seemed questionable whether their inhibitory effects on these kinases
      were responsible for the cytotoxic properties observed in a variety of human
      cancer cell cultures. Accordingly, a COMPARE analysis of the cytotoxicity profile
      of the most cytotoxic member of the series was performed, and the results
      indicated that its cytotoxicity profile was similar to that of antitubulin
      agents. This mechanism of action was supported by demonstrating that most
      compounds in the series were moderately effective as inhibitors of tubulin
      polymerization. This suggests that the lavendustin A analogues reported here, as
      well as some of the previously reported lavendustin A analogues, may be acting as
      cytotoxic agents by a mechanism involving the inhibition of tubulin
      polymerization.

PMID- 11462984
TI  - GnRH antagonists: a new generation of long acting analogues incorporating p
      ureido-phenylalanines at positions 5 and 6.
AB  - A series of antagonists of gonadotropin-releasing hormone (GnRH) of the general
      formula Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph/4Amf(P)-D4Aph/D4Amf(Q)-Leu-ILys-Pro-DAla
      NH2 was synthesized, characterized, and screened for duration of inhibition of
      luteinizing hormone release in a castrated male rat assay. Selected analogues
      were tested in a reporter gene assay (IC50 and pA2) and an in vitro histamine
      release assay. P and Q contain urea/carbamoyl functionalities designed to
      increase potential intra- and intermolecular hydrogen bonding opportunities for
      structural stabilization and peptide/receptor interactions, respectively. These
      substitutions resulted in analogues with increased hydrophilicity and a lesser
      propensity to form gels in aqueous solution than azaline B [Ac-D2Nal-D4Cpa-D3Pal
      Ser-4Aph(Atz)-D4Aph(Atz)-Leu-ILys-Pro-DAla-NH2 with Atz = 3'-amino-1H-1',2',4'
      triazol-5'-yl, 5], and in some cases they resulted in a significant increase in
      duration of action after subcutaneous (s.c.) administration. Ac-D2Nal-D4Cpa-D3Pal
      Ser-4Aph(L-hydroorotyl)-D4Aph(carbamoyl)-Leu-ILys-Pro-DAla-NH2 (acetate salt is
      FE200486) (31) and eight other congeners (20, 35, 37, 39, 41, 45-47) were
      identified that exhibited significantly longer duration of action than acyline
      [Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Ac)-D4Aph(Ac)-Leu-ILys-Pro-DAla-NH2] (6) when
      administered subcutaneously in castrated male rats at a dose of 50 microg in 100
      microL of phosphate buffer. No correlation was found between retention times on a
      C18 reverse phase column using a triethylammonium phosphate buffer at pH 7.0 (a
      measure of hydrophilicity) or affinity in an in vitro human GnRH report gene
      assay (pA2) and duration of action. FE200486 was selected for preclinical
      studies, and some of its properties were compared to those of other clinical
      candidates. In the intact rat, ganirelix, abarelix, azaline B, and FE200486
      inhibited plasma testosterone for 1, 1, 14, and 57 days, respectively, at 2 mg/kg
      s.c. in 5% mannitol (injection volume = 20 microL). Based on the information that
      31, 33, 35 and 37 were significantly shorter acting than acyline or azaline B
      after intravenous administration (100 microg/rat), we surmised that the very long
      duration of action of the related FE200486 (for example) was likely due to unique
      physicochemical properties such as solubility in aqueous milieu, comparatively
      low propensity to form gels, and ability to diffuse at high concentrations in a
      manner similar to that described for slow release formulations of peptides.
      Indeed, in rats injected s.c. with FE200486 (2 mg/kg), plasmatic concentrations
      of FE200486 remained above 5 ng/mL until day 41, and the time after which they
      dropped below 3 ng/mL and plasma LH levels started rising until full recovery was
      reached at day 84 with levels of FE200486 hovering around 1 ng/mL. Additionally,
      FE200486 was less potent at releasing histamine from isolated rat mast cells than
      any of the GnRH antagonists presently described in preclinical reports.

PMID- 11462985
TI  - Synthesis by chemoselective ligation and biological evaluation of novel cell
      permeable PKC-zeta pseudosubstrate lipopeptides.
AB  - The ability of lipopeptides to passively cross the cell membrane opens new
      opportunities for the intracellular delivery of bioactive peptides. However, the
      production of large series of cell-permeable lipopeptides is not trivial due to
      their generally low solubility. We have evaluated the possibility of associating
      the fatty acid to the functional cargo using generally applicable ligation
      chemistries. To this end, we have designed an amphiphilic shuttle in which
      arginine residues served to solubilize the lipid part in aqueous media, during
      both the assembly of the lipopeptide and the cellular assays. Our model peptide,
      the pseudosubstrate sequence of protein kinase C-zeta (PKC-zeta), was associated
      to the pentapeptide Gly-Arg-Gly-Arg-Lys(Pam)-NH2 through thiazolidine, thioether,
      disulfide, or hydrazone linkages. The cytoplasm import of the resulting
      constructs was monitored through the quantification of the apoptosis specifically
      induced by PKC-zeta inhibition. Our observations suggested the interest of this
      noninvasive cellular import method to modulate the activity of an
      intracytoplasmic pharmacological target and showed the influence of a non-amide
      link created between the functional peptide and the lipidic vector: optimal
      results, in terms of both specific activity and low basal cytotoxicity, were
      obtained with the thiazolidine ligation product.

PMID- 11462986
TI  - Calculation of the hydrophobicity of platinum drugs.
AB  - Models of the hydrophobicity of platinum drugs based on exposed surface areas of
      polar and nonpolar atoms are presented. For a total of 24 log P(oct) data, the
      best model resulted in a standard deviation of 0.35 over a range of more than 4
      log units, with regression coefficients in broad agreement with previous models
      of log P(oct) for organic molecules. This model is used to compare log P(oct) to
      cell uptake for five platinum drugs and hence to establish an exponential
      relation between these parameters.

PMID- 11462987
TI  - Bibliography. Current world literature. Lipid metabolism and therapy.

PMID- 11462988
TI  - Bibliography. Current world literature. Nutrition in the intensive care unit.

PMID- 11462989
TI  - Phylogeography, Hybridization and Speciation. Proceedings of a meeting. Aussois,
      France, April 2000.

PMID- 11462990
TI  - 9th International Symposium on Cosmetic Laser Surgery. April 28-30, 2000. Las
      Vegas, Nevada, USA. Abstracts.

PMID- 11462991
TI  - Proceedings of the 18th Workshop of the Scandinavian Society for Cell Toxicology.
      Solentuna, Sweden, 7-10 September 2000.

PMID- 11462992
TI  - VHA, Deloitte & Touche offer strategies for hospitals and health care systems.

PMID- 11462993
TI  - Summaires for patients. In some women, postmenopausal hormone use increases short
      term risk for heart disease, but decreases risk in the long term.

PMID- 11462994
TI  - Patient-initiated treatment of recurrent urinary tract infection in women.

PMID- 11462995
TI  - Summaries for patients. Using multiple drugs in combination helps patients with
      advanced AIDS.

PMID- 11462996
TI  - Summaries for patients. A new anti-inflammatory therapy (Infliximab) for
      complicated sarcoidosis.

PMID- 11462997
TI  - Facility profile. Interior renovation gets a hand. Curtis National Center for
      Treatment of the Hand and Upper Extremity, Baltimore.

PMID- 11462998
TI  - How to define risk factors among cancer patients.

PMID- 11462999
TI  - 'Payer specialists' save nurses time.

PMID- 11463000
TI  - Patient safety alert. Risk management eliminated in wide-ranging program.

PMID- 11463001
TI  - Patient safety alert. Patient safety tool focuses on best practices.

PMID- 11463002
TI  - Patient safety alert. ER demand still rising, endangering patients.

PMID- 11463003
TI  - The eradication of bovine pleuropneumonia: a personal perspective.

PMID- 11463004
TI  - Lipoprotein(a) levels in patients with homozygous familial hypercholesterolaemia.

PMID- 11463006
TI  - Summaries for patients. Detecting pulmonary emboli with helical computed
      tomography.

PMID- 11463005
TI  - Summaries for patients. Using a type of blood pressure medicine, angiotensin
      converting enzyme inhibitors, to prevent worsening of kidney disease unrelated to
      diabetes.

PMID- 11463007
TI  - Summaries for patients. Improving the diagnosis of pulmonary embolism in the
      emergency department.

PMID- 11463008
TI  - Summaries for patients. A new and improved system for excluding the diagnosis of
      deep venous thrombosis.

PMID- 11463009
TI  - Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or
      BRCA2 mutation.
AB  - BACKGROUND: Women with a BRCA1 or BRCA2 mutation have a high risk of breast
      cancer and may choose to undergo prophylactic bilateral total mastectomy. We
      investigated the efficacy of this procedure in such women. METHODS: We conducted
      a prospective study of 139 women with a pathogenic BRCA1 or BRCA2 mutation who
      were enrolled in a breast-cancer surveillance program at the Rotterdam Family
      Cancer Clinic. At the time of enrollment, none of the women had a history of
      breast cancer. Seventy-six of these women eventually underwent prophylactic
      mastectomy, and the other 63 remained under regular surveillance. The effect of
      mastectomy on the incidence of breast cancer was analyzed by the Cox proportional
      hazards method in which mastectomy was modeled as a time-dependent covariate.
      RESULTS: No cases of breast cancer were observed after prophylactic mastectomy
      after a mean (+/-SE) follow-up of 2.9+/-1.4 years, whereas eight breast cancers
      developed in women under regular surveillance after a mean follow-up of 3.0+/-1.5
      years (P=0.003; hazard ratio, 0; 95 percent confidence interval, 0 to 0.36). The
      actuarial mean five-year incidence of breast cancer among all women in the
      surveillance group was 17+/-7 percent. On the basis of an exponential model, the
      yearly incidence of breast cancer in this group was 2.5 percent. The observed
      number of breast cancers in the surveillance group was consistent with the
      expected number (ratio of observed to expected cases, 1.2; 95 percent confidence
      interval, 0.4 to 3.7; P=0.80). CONCLUSIONS: In women with a BRCA1 or BRCA2
      mutation, prophylactic bilateral total mastectomy reduces the incidence of breast
      cancer at three years of follow-up.

PMID- 11463010
TI  - Three months versus one year of oral anticoagulant therapy for idiopathic deep
      venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators.
AB  - BACKGROUND: In patients with idiopathic deep venous thrombosis, continuing
      anticoagulant therapy beyond three months is associated with a reduced incidence
      of recurrent thrombosis during the period of therapy. Whether this benefit
      persists after anticoagulant therapy is discontinued is controversial. METHODS:
      Patients with a first episode of idiopathic proximal deep venous thrombosis who
      had completed three months of oral anticoagulant therapy (with warfarin, in 97
      percent of the cases and acenocoumarol in 3 percent) were randomly assigned to
      the discontinuation of oral anticoagulants or to their continuation for nine
      additional months. The primary study outcome was recurrence of symptomatic,
      objectively confirmed venous thromboembolism during at least two years of follow
      up. RESULTS: The primary intention-to-treat analysis showed that of 134 patients
      assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous
      thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with
      21 of 133 patients assigned to the discontinuation of oral anticoagulant therapy
      (15.8 percent; average follow-up, 37.2 months), resulting in a relative risk of
      0.99 (95 percent confidence interval, 0.57 to 1.73). During the initial nine
      months after randomization (after all patients received three months of therapy),
      1 patient had a recurrence while receiving oral anticoagulant therapy (0.7
      percent), as compared with 11 of the patients assigned to the discontinuation of
      oral anticoagulant therapy (8.3 percent; P=0.003). The incidence of recurrence
      after the discontinuation of treatment was 5.1 percent per patient-year in
      patients in whom oral anticoagulant therapy was discontinued after 3 months (95
      percent confidence interval, 3.2 to 7.5 percent; average interval since
      discontinuation, 37.2 months) and 5.0 percent per patient-year in patients who
      received an additional 9 months of oral anticoagulant therapy (95 percent
      confidence interval, 3.1 to 7.8 percent; average interval since discontinuation,
      29.4 months). None of the recurrences were fatal. Four patients had non-fatal
      major bleeding during the extended period of anticoagulant therapy (3.0 percent).
      CONCLUSIONS: In patients with idiopathic deep venous thrombosis, the clinical
      benefit associated with extending the duration of anticoagulant therapy to one
      year is not maintained after the therapy is discontinued.

PMID- 11463011
TI  - The treatment of multidrug-resistant tuberculosis in Turkey.
AB  - BACKGROUND: We evaluated the results of treatment in 158 consecutive patients
      with multidrug-resistant tuberculosis who were treated at our center in Istanbul.
      METHODS: A total of 21 female patients and 137 male patients (age range, 15 to 68
      years) received treatment for multidrug-resistant tuberculosis between March 1992
      and October 1999. The patients had previously received a mean of 5.7
      antituberculosis drugs and were infected with organisms that were resistant to a
      mean of 4.4 drugs. All patients were infected with organisms that were resistant
      to both isoniazid and rifampicin. The regimens we used were selected on the basis
      of previous treatment protocols and the results of susceptibility tests. All
      patients received at least three drugs thought to be active; the treatment was
      continued for at least 18 months after the conversion to a negative culture and
      for at least 24 months in the absence of first-line drugs. RESULTS: The mean
      number of drugs given during the study was 5.5 (range, 3 to 9). Surgical
      resection was performed in 36 patients. Adverse effects led to discontinuation of
      one or more drugs in 62 patients (39 percent). Cultures became negative in 150
      patients (95 percent) after a mean of 1.9 months (range, 1 to 9). The overall
      success rate of treatment was 77 percent, with cures in 78 patients (49 percent)
      and probable cures in 43 (27 percent). Treatment failed in 13 patients (8
      percent). Seven patients died (4 percent). Seventeen patients (11 percent) did
      not complete the treatment regimen. The patients with unsuccessful outcomes were
      older than those with successful outcomes (mean age, 42 years vs. 36 years;
      P=0.008), had received a larger number of drugs previously (median, six vs. five;
      P=0.048), were more likely to have been treated previously with ofloxacin (57
      percent vs. 30 percent, P=0.004), and were less likely to have received ofloxacin
      as part of the study protocol (65 percent vs. 84 percent, P=0.018). Thirty-eight
      percent of the patients with unsuccessful outcomes were infected with organisms
      that were resistant to more than five drugs. In a step-down logistic-regression
      analysis, a successful outcome was independently associated with a younger age
      (P=0.013) and the absence of previous treatment with ofloxacin (P=0.005).
      CONCLUSIONS: Most patients with multidrug-resistant tuberculosis can be cured
      with the use of appropriate, intensive treatment regimens.

PMID- 11463012
TI  - Defective urinary concentrating ability due to a complete deficiency of aquaporin
      1.

PMID- 11463013
TI  - Images in clinical medicine. Liver metastases from lung cancer.

PMID- 11463014
TI  - The influence of hospital volume on survival after resection for lung cancer.
AB  - BACKGROUND: Among patients who have undergone high-risk operations for cancer,
      postoperative mortality rates are often lower at hospitals where more of these
      procedures are performed. We undertook a population-based study to estimate the
      extent to which the number of procedures performed at a hospital (hospital
      volume) is associated with survival after resection for lung cancer. METHODS: We
      studied patients 65 years old or older who received a diagnosis of stage I, II,
      or IIIA non-small-cell lung cancer between 1985 and 1996, resided in 1 of the 10
      study areas covered by the Surveillance, Epidemiology, and End Results Program,
      and underwent surgery at a hospital that participates in the Nationwide Inpatient
      Sample (2118 patients and 76 hospitals). RESULTS: The volume of procedures at the
      hospital was positively associated with the survival of patients (P<0.001). Five
      years after surgery, 44 percent of patients who underwent operations at the
      hospitals with the highest volume were alive, as compared with 33 percent of
      those who underwent operations at the hospitals with the lowest volume. Patients
      at the highest-volume hospitals also had lower rates of postoperative
      complications (20 percent vs. 44 percent) and lower 30-day mortality (3 percent
      vs. 6 percent) than those at the lowest-volume hospitals. CONCLUSIONS: Patients
      who undergo resection for lung cancer at hospitals that perform large numbers of
      such procedures are likely to survive longer than patients who have such surgery
      at hospitals with a low volume of lung-resection procedures.

PMID- 11463015
TI  - Management of tuberculosis in the United States.

PMID- 11463016
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 22-2001. A 25-year-old woman with fever and abnormal liver
      function.

PMID- 11463017
TI  - Prophylactic mastectomy for women with BRCA1 and BRCA2 mutations--facts and
      controversy.

PMID- 11463018
TI  - The major infectious diseases in the world--to treat or not to treat?

PMID- 11463019
TI  - Is it justifiable to withhold treatment for hepatitis C from illicit-drug users?

PMID- 11463020
TI  - Treatment of chronic hepatitis C in active drug users.

PMID- 11463021
TI  - Recombinant human activated protein C for severe sepsis.

PMID- 11463022
TI  - Recombinant human activated protein C for severe sepsis.

PMID- 11463023
TI  - Recombinant human activated protein C for severe sepsis.

PMID- 11463024
TI  - Recombinant human activated protein C for severe sepsis.

PMID- 11463025
TI  - Renal-artery stenosis.

PMID- 11463026
TI  - Renal-artery stenosis.

PMID- 11463027
TI  - Genetic variation in alcohol dehydrogenase and myocardial infarction.

PMID- 11463028
TI  - Appendectomy and protection against ulcerative colitis.

PMID- 11463029
TI  - Appendectomy and protection against ulcerative colitis.

PMID- 11463030
TI  - Appendectomy and protection against ulcerative colitis.

PMID- 11463031
TI  - Myocarditis and cardiomyopathy associated with clozapine use in the United
      States.

PMID- 11463033
TI  - JAMA patient page. Organ donation. Share life by donating your organs and
      tissues.

PMID- 11463032
TI  - Pamidronate for bone pain from osteolytic lesions in Langerhans'-cell
      histiocytosis.

PMID- 11463034
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States and worldwide, 2000-01 season, and composition of the 2001-02
      influenza vaccine.

PMID- 11463035
TI  - From the Centers for Disease Control and Prevention. Fatal pediatric poisoning-
      New Hampshire, 2000.

PMID- 11463036
TI  - From the Centers for Disease Control and Prevention. First reports of AIDS.

PMID- 11463037
TI  - From the Centers for Disease Control and Prevention. The 20th year of AIDS: a
      time to re-energize prevention.

PMID- 11463038
TI  - From the Centers for Disease Control and Prevention. Shortage of spectinomycin.

PMID- 11463039
TI  - Spinal anaesthesia and conus damage.

PMID- 11463040
TI  - A simple technique to reduce the incidence of accidental dural puncture.

PMID- 11463041
TI  - What's the point?

PMID- 11463042
TI  - Effect of ropivacaine on platelet function.

PMID- 11463043
TI  - Diclofenac suppositories--potential for drug error?

PMID- 11463044
TI  - Pre-filled drugs for the obstetric theatre.

PMID- 11463045
TI  - Pre-filled ephedrine syringes.

PMID- 11463046
TI  - Which side?

PMID- 11463047
TI  - Aerial somersault performance under three visual conditions.
AB  - Experiments were designed to examine the visual contributions to performance of
      back aerial double somersaults by collegiate acrobats. Somersaults were performed
      on a trampoline under three visual conditions: (a) NORMAL acuity; (b) REDUCED
      acuity (subjects wore special contacts that blocked light reflected onto the
      central retina); and (c) NO VISION. Videotaped skill performances were rated by
      two NCAA judges and digitized for kinematic analyses. Subjects' performance
      scores were similar in NORMAL and REDUCED conditions and lowest in the NO VISION
      condition. Control of body movement, indicated by time-to-contact, was most
      variable in the NO VISION condition. Profiles of angular head and neck velocity
      revealed that when subjects could see, they slowed their heads prior to touchdown
      in time to process optical flow information and prepare for landing. There was
      not always enough time to process vision associated with object identification
      and prepare for touchdown. It was concluded that collegiate acrobats do not need
      to identify objects for their best back aerial double somersault performance.

PMID- 11463048
TI  - Randomized double-blind placebo controlled trial of the effect of botulinum toxin
      on walking in cerebral palsy.

PMID- 11463049
TI  - Adverse effects of early dexamethasone treatment in extremely-low-birth-weight
      infants.

PMID- 11463050
TI  - Promotion of Breastfeeding Intervention Trial (PROBIT) a randomized trial in the
      Republic of Belarus.

PMID- 11463051
TI  - [Crystalloid versus colloid. A never ending story?].

PMID- 11463052
TI  - [Small volume--large benefits?].

PMID- 11463056
TI  - From the Centers for Disease Control and Prevention. Exposure to patients with
      meningococcal disease on aircraft--United States, 1999-2001.

PMID- 11463057
TI  - From the Centers for Disease Control and Prevention. University Outbreak of
      Calcivirus infection mistakenly attributed to Shiga toxin-producing Escherichia
      Coli O157:H7--Virginia, 2000.

PMID- 11463058
TI  - JAMA Patient page. When gambling becomes a bad bet.

PMID- 11463059
TI  - Lipoprotein(a)is an important genetic risk for coronary artery disease in Asian
      Indians.

PMID- 11463060
TI  - Low-density lipoprotein apheresis in homozygous familial hypercholesterolemia.

PMID- 11463061
TI  - Atorvastatin versus micronized fenofibrate in the treatment of patients with
      mixed hyperlipoproteinemia.

PMID- 11463062
TI  - Cuban medicine.

PMID- 11463063
TI  - Diagnosis of proximal right coronary artery occlusion using ST elevation ratio in
      lead III > II.

PMID- 11463064
TI  - Delaware/Hudson Valley hot spot for biotechnology.

PMID- 11463065
TI  - Current world literature.

PMID- 11463066
TI  - An overview of animal models in experimental schistosomiasis and refinements in
      the use of non-human primates.
AB  - The complex nature of the schistosome parasite and its interaction with the
      mammalian host necessitates the continued use of live intact animal models in
      schistosomiasis research. This review acknowledges this necessity and highlights
      some of the important insights into the pathogenesis of the disease that have
      been gained from using various animal models. The use of non-human primates as
      more relevant models of human schistosomiasis is stated. In addition, the
      importance of animal welfare consideration when using primates for research is
      emphasized. Finally, some guidelines for the refined capture, handling and early
      humane endpoints for non-human primates to be used in experimental
      schistosomiasis are suggested.

PMID- 11463067
TI  - Psychological distress, hopelessness and welfare.
AB  - This article assesses the validity of the claim that welfare in itself has
      deleterious psychological consequences for single mothers. The analysis compares
      single mothers who are recipients of AFDC with single mothers who are not
      recipients in terms of their depressive symptoms (as measured by the CES-D) and
      hopelessness (as measured by Pearlin Mastery Scale). The analysis uses data from
      the National Longitudinal Survey of Youth and the National Survey of Families and
      Households. The authors find that higher levels of both depression and
      hopelessness among welfare recipients can be explained by their material hardship
      rather than the stigma attached to welfare. They show that AFDC recipients report
      similar levels of depression and hopelessness as jobless non-recipients as well
      as low-wage non-recipients. An additional finding is that long-term welfare
      recipients do not experience greater emotional problems than short-term welfare
      recipients. Finally, the paper shows that feelings of hopelessness mediate the
      relationship between material deprivation and psychological distress for both
      recipients and non-recipients.

PMID- 11463068
TI  - Scale and structure of capitated physician organizations in California.
AB  - Physician organizations in California broke new ground in the 1980s by accepting
      capitated contracts and taking on utilization management functions. In this paper
      we present new data that document the scale, structure, and vertical affiliations
      of physician organizations that accept capitation in California. We provide
      information on capitated enrollment, the share of revenue derived by physician
      organizations from capitation contracts, and the scope of risk sharing with
      health maintenance organizations (HMOs). Capitation contracts and risk sharing
      dominate payment arrangements with HMOs. Physician organizations appear to have
      responded to capitation by affiliating with hospitals and management companies,
      adopting hybrid organizational structures, and consolidating into larger
      entities.

PMID- 11463069
TI  - Medicare+Choice: an interim report card.
AB  - While the aim of Medicare+Choice (M+C) was to expand choice, the choices
      available to Medicare beneficiaries have diminished since its inception: Existing
      plans have withdrawn from M+C, few new plans have entered the program from among
      the newly authorized plan types, greater choice has not developed in areas that
      lacked choice, and the inequities in benefits and offerings between higher- and
      lower-paid areas of the country have widened rather than narrowed. Operational
      constraints probably explain the most immediate declines in M+C enrollment, but
      Congress's ability to foster success for M+C will ultimately depend on the way in
      which historical tensions related to competing goals and ideologies for the
      Medicare program are resolved.

PMID- 11463070
TI  - Market failure? Individual insurance markets for older Americans.
AB  - This study examines the viability of tax credits and nongroup markets for
      covering uninsured adults ages fifty to sixty-four. We find that adults in this
      age group covered by nongroup plans tend to be healthier and wealthier than the
      average for their peers, yet more of them go without care and experience high
      medical bills relative to their incomes. Individual-market premiums rise steeply
      with age in most states and are well above employer-group rates. Costs are likely
      to be unaffordable for most uninsured older adults, even with large tax credits
      or in states with community rating. These findings indicate a need to include
      risk and age pooling to reach the uninsured in this age group.

PMID- 11463071
TI  - Hospital mergers and savings for consumers: exploring new evidence.
AB  - This study analyzes changes in costs and prices from 1989 to 1997 for 1,767 short
      term hospitals, including 204 hospitals involved in mergers; 653 hospitals that
      were rivals to these merging hospitals; and 910 nonmerging nonrival hospitals. We
      find that merging hospitals generally had lower growth in costs and prices
      compared with their rivals and also with nonmerging nonrival hospitals. We find
      that the presence and extent of these savings varied based on market and hospital
      conditions. However, our findings suggest that cost and price savings resulting
      from mergers may be smaller than estimated in earlier studies, especially through
      our comparison of merging hospitals with their rivals.

PMID- 11463072
TI  - How did safety-net hospitals cope in the 1990s?

PMID- 11463073
TI  - The effect of reforms on spending for veterans' substance abuse treatment, 1993
      1999.

PMID- 11463074
TI  - Politics and the public hospital in our capital.

PMID- 11463075
TI  - Making a public hospital work.

PMID- 11463076
TI  - Medicare beneficiaries' costs of care in the last year of life.
AB  - This paper profiles Medicare beneficiaries' costs for care in the last year of
      life. About one-quarter of Medicare outlays are for the last year of life,
      unchanged from twenty years ago. Costs reflect care for multiple severe illnesses
      typically present near death. Thirty-eight percent of beneficiaries have some
      nursing home stay in the year of their death; hospice is now used by half of
      Medicare cancer decedents and 19 percent of Medicare decedents overall. African
      Americans have much higher end-of-life costs than others have, an unexpected
      finding in light of their generally lower health care spending.

PMID- 11463077
TI  - Embraceable you: how employers influence health plan enrollment.
AB  - Based on data from a 1999 national survey of 1,939 randomly selected employers,
      this paper examines the policies that affect the percentage of workers eligible
      for and enrolled in a firm's health plan. In 1994, 14 percent of employees worked
      for a firm offering cash-back payments, but fewer than 1 percent worked for a
      firm with income-related premiums or deductibles. The strongest determinants of
      eligibility rates are the waiting time for new employees before they are deemed
      eligible, and eligibility standards for part-time workers. The primary
      determinants of the take-up rate are lowest monthly employee contribution for
      single coverage, and the percentage of the workforce earning less than $20,000
      per year.

PMID- 11463078
TI  - Are Fortune 100 companies responsive to chronically ill workers?
AB  - We conducted a survey of Fortune 100 companies to determine their response to the
      growing number of employees with chronic conditions. We found that although all
      companies cover some services that are particularly beneficial to persons with
      chronic conditions, gaps in coverage remain. We also found large variations in
      cost-sharing mechanisms, number of covered visits, and lifetime maximum benefit
      provisions, which are especially important to persons with chronic conditions. In
      general, for persons with chronic conditions the benefits offered by these
      Fortune 100 companies are superior to those offered by Medicare.

PMID- 11463079
TI  - Prevalence of selected employer health insurance purchasing strategies in 1997.
AB  - This paper provides information about the nationwide prevalence of selected
      employer health insurance purchasing strategies. These strategies include raising
      the share of medical costs borne by employees; the use of quality information in
      choosing which plans to offer; and direct contracting with provider systems. The
      data are primarily from the 1997 Robert Wood Johnson Foundation Employer Health
      Insurance Survey.

PMID- 11463080
TI  - Use of physician assistants and nurse practitioners in primary care, 1995-1999.
AB  - Federal policies and state legislation encourage the use of physician assistants
      (PAs) and nurse practitioners (NPs) in primary care, although the nature of their
      work has not been fully analyzed. In this paper we analyze primary care physician
      office encounter data from the 1995-1999 National Ambulatory Medical Care
      Surveys. About one-quarter of primary care office-based physicians used PAs
      and/or NPs for an average of 11 percent of visits. The mean age of patients seen
      by physicians was greater than that for PAs or NPs. NPs provided
      counseling/education during a higher proportion of visits than did PAs or
      physicians. Overall, this study suggests that PAs and NPs are providing primary
      care in a way that is similar to physician care.

PMID- 11463081
TI  - Reinventing a multicounty behavioral health care system: the local philanthropy
      as change agent.

PMID- 11463082
TI  - Authors respond to WHO critics.

PMID- 11463083
TI  - More debate on paying for GME.

PMID- 11463084
TI  - Ways to address medical errors.

PMID- 11463086
TI  - Use of consumer surveys.

PMID- 11463085
TI  - Admitting mistakes is not enough.

PMID- 11463087
TI  - Doctors' views of Medicare payment levels.

PMID- 11463088
TI  - Fraud-and-abuse enforcement in Medicare: finding middle ground.
AB  - Medicare fraud and abuse cost billions of dollars each year. Yet Congress is
      considering legislation to hamper enforcement. Providers' anger over enforcement
      led to a congressional compromise several years ago to limit excesses. If
      providers and their advocates were to hobble enforcement, this could provoke a
      backlash. Instead, the existing compromise should be strengthened to accommodate
      legitimate provider concerns while allowing enforcement against major fraud and
      abuse. Government should further confine, structure, and check its discretion in
      applying the False Claims Act. Enhancing the Health Care Financing
      Administration's capacity to ensure that contractors pay claims properly would
      remove additional points of friction.

PMID- 11463089
TI  - How managed care can be ethical.
AB  - The growth of managed care in the United States has been paralleled by a rising
      tide of anti-managed care sentiment. The "managed care problem" is understood
      generally as the need to protect individuals against large companies that care
      more about their bottom line than about people. The premise of the BEST (Best
      Ethical Strategies for Managed Care) project is that the "managed care problem"
      is best understood as an ethical problem--a conflict of values that arises as the
      country changes from a patient-centered to a population-centered approach to
      health care. The BEST project team worked with nine managed care organizations to
      identify their most intractable problems. The team redefined these problems in
      terms of ethical dilemmas, then studied each organization in search of
      innovative, exemplary approaches. These exemplary approaches are being shared
      publicly with the aim that they be adapted and adopted by other organizations
      facing similar difficulties and by regulators and legislators hoping to improve
      the health care system.

PMID- 11463090
TI  - Full parity: steps toward treatment equity for mental and addictive disorders.
AB  - The 1996 Mental Health Parity Act requiring equal annual and lifetime dollar
      limits for mental health benefits is to sunset 30 September 2001. This paper
      reviews the impact and limitations of both this law and existing state provisions
      and describes recent research on the actual and projected costs associated with
      such laws. We contend that full parity provided within the context of managed
      care not only is possible, but represents a "sequential" rather than a final step
      toward the broader goal of achieving equity in the treatment of persons with
      mental and addictive disorders.

PMID- 11463091
TI  - Toward full mental health parity and beyond.
AB  - The 1996 Mental Health Parity Act (MHPA), which became effective in January 1998,
      is scheduled to expire in September 2001. This paper examines what the MHPA
      accomplished and steps toward more comprehensive parity. We explain the strategic
      and self-reinforcing link of parity with managed behavioral health care and
      conclude that the current path will be difficult to reverse. The paper ends with
      a discussion of what might be behind the claims that full parity in mental health
      benefits is insufficient to achieve true equity and whether additional steps
      beyond full parity appear realistic or even desirable.

PMID- 11463092
TI  - Parity or insurance mandate? The case for mental health parity in Kansas.

PMID- 11463093
TI  - Consumers versus managed care: the new class actions.
AB  - The plaintiffs in pending consumer class-action lawsuits against health
      maintenance organizations (HMOs) should fail in their claims for damages for
      fraud under federal anti-racketeering legislation. Although HMOs have regularly
      failed to disclose their business methods and have not strictly honored their
      contractual coverage promises, the circumstances in which they introduced cost
      controls into a market sadly lacking them suggest motives not deserving punitive
      sanctions. Courts could easily find that HMOs violated the Employee Retirement
      Income Security Act (ERISA), however. Injunctive relief compelling more extensive
      disclosures and clearer contracts might well legitimize HMOs' methods and
      generally improve the performance of the health care marketplace.

PMID- 11463094
TI  - Physician organization in California: crisis and opportunity.
AB  - Many of the 250 physician organizations that provide care to California's sixteen
      million health maintenance organization enrollees are in a state of crisis,
      squeezed between constrained revenues, rising practice costs, and consumer
      sentiment that favors unconstrained choice over integrated delivery. Medical
      groups and independent practice associations are retrenching to their core
      geographic areas, reducing capitation for drug benefits and hospital services,
      and abandoning dreams of displacing health plans. Consolidation is accelerating
      in some areas, as medical groups join with hospitals to extract higher payment
      rates from insurers and employers. The conjunction of consumerism and premium
      inflation creates new opportunities for organizations that truly can manage
      health care, but the challenges roiling California's medical groups may preclude
      meaningful efforts to seize the initiative.

PMID- 11463095
TI  - Canaries in a coal mine: California physician groups and competition.
AB  - Health care organizations may compete by developing organized processes to
      improve quality and increase efficiency, or may focus on growing to increase
      negotiating leverage and on controlling costs through withholding appropriate
      care and avoiding sick patients. This paper describes key ways in which public
      and private policy decisions create incentives that influence the competitive
      focus of physician groups in California, a state in which physician groups and
      health maintenance organizations are prevalent. These policies do not manage
      competition in optimal ways: They reward groups for market leverage and
      controlling costs while failing to fully reward quality and efficiency.

PMID- 11463096
TI  - Persistence of herpesvirus of eel Herpesvirus anguillae in farmed European eel
      Anguilla anguilla.
AB  - Herpesvirus of eel Herpesvirus anguillae (HVA) was isolated repeatedly from
      farmed eel of an outwardly healthy stock, but virus isolation was much greater in
      an experimental group of fish that were injected with dexamethasone. The results
      suggest that HVA can establish a latent infection in eel. Previous exposure of
      these eels to HVA virus was shown by detection of HVA-specific antibodies. These
      eels did not show clinical signs after a secondary infection with HVA. Tracing of
      seropositive eel stocks, which had previous contact with HVA, and of HVA carrier
      fish can be useful to control disease outbreaks due to HVA infection.

PMID- 11463097
TI  - Comparison of single-round polymerase chain reaction (PCR) and pepsin-trypsin
      digest (PTD) methods for detection of Myxobolus cerebralis.
AB  - Single-round polymerase chain reaction (PCR) and pepsin-trypsin digest (PTD)
      methods were compared for the detection of Myxobolus cerebralis. Parallel tests
      were conducted on a total of 1743 free-ranging and 400 hatchery-reared salmonids.
      Concurrent results were found in 84.6% of the free-ranging fish samples, and
      83.5% of the hatchery samples. PCR identified M. cerebralis more frequently than
      did PTD, and did so in many geographic locations previously considered free of
      the parasite. Average myxospore count by PTD among both free-ranging and hatchery
      fish increased significantly (p < 0.001) with a subjective evaluation of amplicon
      staining intensity.

PMID- 11463098
TI  - Effect of lectins on the invasion of Ichthyophthirius theront to channel catfish
      tissue.
AB  - This study determined the effects of lectin binding to theronts of
      Ichthyophthirius multifiliis on theront immobilization, invasion, trophont
      development and survival in channel catfish Ictalurus punctatus excised fins in
      vitro. Soybean agglutinin (SBA), lentil agglutinin (LCA), gorse agglutinin (UEA
      I) and wheat germ agglutinin (WGA) were used to treat theronts. Percentages of
      theronts immobilized by 4 lectins ranged from 12.0 to 19.4% at a concentration of
      1000 microg ml(-1). These lectins bound more than half of the theronts at a
      concentration of 50 microg ml(-1). More theronts were labeled by SBA and WGA than
      by lectin LCA at concentrations of 50 and 100 microg ml(-1), respectively. The
      binding of these lectins to theronts indicated that monosaccharides (D-galactose,
      L-fucose, D-mannose and D-glucose) and amino sugar derivatives (N
      acetylgalactosamine and N-acetylglucosamine) were present on the surface of
      theronts. Invasion was reduced significantly for theronts treated with LCA, UEA-I
      and WGA. No difference in invasion was found between control and SBA bound
      theronts (p > 0.05). The binding of lectin LCA, UEA-I and WGA to theronts
      significantly reduced the development of trophonts (p < 0.05). The mean volumes
      of trophonts labeled with these 3 lectins were smaller than volumes in control
      trophonts from 8 to 48 h after exposure. Survival was lower in trophonts labeled
      with lectins than in control trophonts at 48 h after exposure.

PMID- 11463099
TI  - Analysis of Kudoa thyrsites (Myxozoa: Myxosporea) spore antigens using monoclonal
      antibodies.
AB  - A method employing Percoll gradient centrifugation was developed to purify Kudoa
      thyrsites spores from somatic muscle tissue of Atlantic salmon Salmo salar.
      Highly purified spores were then used to immunize inbred BALB/c mice for
      derivation of hybridomas secreting Kudoa-specific monoclonal antibodies (mAbs).
      Analysis of mAbs by immunofluorescence microscopy and flow cytometry showed that
      several were specific for antigens on the surface of K. thyrsites spores whereas
      other mAbs reacted with polar capsules or with polar filaments of spores of K.
      thyrsites, K. paniformis and K. crumena. Immunoblots on spore lysates using the
      surface-binding mAbs showed a broad band of 46 to > 220 kDa, whereas mAbs
      specific for antigens of polar capsules and polar filaments detected sharper
      bands of various molecular masses, depending on the Kudoa species. The dominant
      epitope of the K. thyrsites spore surface antigen was shown to be carbohydrate as
      determined by its sensitivity to treatment with anhydrous trifluoromethane
      sulfonic acid and by its resistance to treatment with Proteinase K.
      Immunofluorescence microscopy using the K. thyrsites-specific mAbs on isolated,
      intact, permeabilized plasmodia and on thin sections of somatic muscle tissue
      containing plasmodia revealed intense labeling of spores both within the spore
      producing plasmodia and in the flesh of infected Atlantic salmon. As few as 100
      spores were detected by immunoblotting, indicating that these mAbs have potential
      for use in developing a field-based diagnostic test.

PMID- 11463100
TI  - Fitness of the marine parasitic nematode Anisakis simplex s. str. in temperate
      waters of the NE Atlantic.
AB  - In temperate waters of the NE Atlantic, third-stage larvae of Anisakis simplex
      sensu stricto collected from 3 paratenic host species were identified by
      restriction fragment length polymorphisms. The condition of wild larval
      infrapopulations was assessed by examining morphometric and growth
      characteristics. The differentiation patterns and the excretory/secretory
      products of larvae grown in vitro were also examined. An extensive morphometric,
      growth and differentiation variability was found between parasite larvae
      collected from different paratenic host sources. Nematode infrapopulation larvae
      from the squid comprise those smaller individuals with the lowest values of
      survival rates and moult success. It may be then concluded that the fitness of A.
      simplex s. str. larvae is not the best possible in the squid, which impaired the
      competitiveness of the parasite and its chances of developing into an adult. This
      suggests that the microenvironments impaired by the paratenic host may provide
      larval infrapopulations with unique ecological factors probably influencing its
      recruitment to the final host populations.

PMID- 11463101
TI  - Effects of trematode infection on metabolism and activity in a freshwater snail,
      Semisulcospira libertina.
AB  - Changes in the metabolism and activity of the freshwater snail Semisulcospira
      libertina infected with larval trematodes were studied experimentally. In snails
      up to 11 mm in shell width, crawling distance, feeding frequency, and the
      proportion of individuals located on vertical walls did not differ among snails
      infected with mature or immature cercariae, or uninfected snails (p > 0.05). In
      snails larger than 11 mm, individuals infected with mature cercariae tended to
      feed more frequently during the light period (p = 0.0081), but the distance they
      crawled and the proportion of individuals located on vertical walls did not
      differ, regardless of infection (p > 0.05). Infection with mature cercariae
      significantly increased the oxygen consumption rate (p = 0.016), which was
      measured only in the large size.

PMID- 11463102
TI  - A model of salmon louse production in Norway: effects of increasing salmon
      production and public management measures.
AB  - Salmon lice Lepeophtheirus salmonis Kroyer have caused disease problems in farmed
      Atlantic salmon Salmo salar L. since the mid-1970s in Norway. High infection
      intensities and premature return of wild sea trout Salmo trutta L. were first
      reported in 1992. Later emaciated wild Atlantic salmon smolts carrying large
      amounts of lice have been observed both in fjords and offshore. The Norwegian
      Animal Health Authority regulations to control the problem, which came into
      operation in 1998, included compulsory louse level monitoring in farms and
      maximum legal numbers of lice per fish. Here, we present a model of salmon louse
      egg production in Norway and show that the effect of the current public
      management strategy is critically dependent on the yearly increase in salmon
      production. This is because the infection pressure is the product of the number
      of fish in the system, and the number of lice per fish. Due to the much larger
      number of farmed than wild salmonids, it is highly likely that lice originating
      from farmed salmon infect wild stock. Estimated tolerance limits for wild
      salmonids vary widely, and the level of louse egg production in farms which would
      be needed to decimate wild populations is not known. Two possible thresholds for
      total lice egg production are investigated: (1) 1986 to 1987 level (i.e. before
      adverse effects on sea trout were recorded), and (2) a level corresponding to a
      doubling of the estimated natural infection pressure. The farm lice per fish
      limits that would have to be observed to keep louse production within the 2
      thresholds are calculated for the period 1986 to 2005. A steady decrease in the
      permitted number of lice per fish may keep the total louse production stable, but
      the number of salmon required for verification of lice numbers will increase as
      the prevalence to be verified is decreased. At threshold (2), the model estimated
      that lice limits should have been 0.05 louse per fish in 1999. This would require
      60 fish from each pen to be collected, anaesthetised and examined for a good
      estimate at a confidence level of 95%. Such sample numbers are likely to be
      opposed by farmers. The use of national delousing programs to solve the problem
      is discussed.

PMID- 11463103
TI  - Karyomegaly in Baryancistrus sp. (Loricaridae) from Amazonian Brazil.
AB  - Vesicular karyomegaly of the liver hepatocytes is described from Baryancistrus
      sp. (Loricaridae), in 3 out of 7 fish, collected from Rio Xingu in central
      Amazonian (neutral water) Brazil and kept about 2 wk in a holding facility fed
      with acid water (pH 5.0 to 5.5). Altered cells also occurred in the gill
      epithelium. The vesicles in the liver were shown to contain a periodic acid
      Schiff (PAS)-positive substance or residue.

PMID- 11463104
TI  - Common sculpin Cottus gobio as a natural paratenic host of Proteocephalus
      longicollis (Cestoda: Proteocephalidae), a parasite of salmonids, in Europe.
AB  - Common sculpins Cottus gobio L. (Pisces: Cottidae), from the Mlynsky Brook near
      Ceske Zleby in the Sumava National Park, southwestern Bohemia, Czech Republic,
      were found to harbour in their intestines juvenile cestodes Proteocephalus
      longicollis (Zeder, 1800), a common parasite of holarctic salmonids, with a
      prevalence of 60% and intensity of 1 to 11 (mean 5) parasites per fish;
      undoubtedly, these prey fish serve as paratenic hosts. In this locality, the
      definitive host of P. longicollis is the brown trout Salmo trutta m. fario L.,
      large specimens of which apparently acquire infection of this parasite by feeding
      on infected sculpins. C. gobio is the first known natural paratenic host of P.
      longicollis in Europe.

PMID- 11463105
TI  - Transmission of white spot syndrome virus (WSSV) to Litopenaeus vannamei from
      infected cephalothorax, abdomen, or whole shrimp cadaver.
AB  - Shrimp viruses can remain infectious in frozen shrimp tissue and have been found
      in frozen commodity shrimp. Therefore, the threat of viral outbreaks in wild and
      cultured shrimp via frozen commodity shrimp exists. Because frozen shrimp are
      imported with and without the cephalothorax, more knowledge is needed concerning
      the infectivity of a cephalothorax relative to that of an abdomen. We compared
      the mortality rates from shrimp exposed to a WSSV-infected cephalothorax,
      abdomen, or whole shrimp cadaver. Estimates of transmission coefficients from the
      exposures to the infected cephalothorax, abdomen, or whole shrimp were also
      calculated because the transmission coefficients account for differences in the
      initial doses. In addition, we compared the variability in infectivity of pieces
      of shrimp by feeding 24 equal-sized pieces of cephalothorax and abdomen to 24
      individually isolated shrimp. In Expt 1, susceptible shrimp did not completely
      consume the infected abdomen, and a significant difference was detected among
      shrimp exposed to the abdomen (mortality rate = 0.40), cephalothorax (mortality
      rate = 0.75), and whole shrimp cadaver (mortality rate = 0.67). The calculated
      transmission coefficients were 0.95 from an infected cephalothorax, 0.59 from an
      infected abdomen, and 0.69 from an infected whole shrimp cadaver. In Expt 2,
      susceptible shrimp were starved to ensure complete ingestion of each dose. No
      significant difference was observed in the estimated mortality rates from an
      infected cephalothorax (0.58), abdomen (0.63), or whole shrimp (0.67). The
      calculated transmission coefficients were 0.84 from an infected cephalothorax,
      0.83 from an infected abdomen, and 0.60 from an infected whole shrimp cadaver. In
      Expt 3, no difference was observed in the mortality rates resulting from
      exposures to pieces of infected cephalothorax (0.57) or abdomen (0.58). Our
      results suggested that there was no difference in the viral loads of a WSSV
      infected cephalothorax or abdomen, but that the cephalothorax was more
      infectious, probably because it was more palatable. In addition, our results are
      inconsistent with some assumptions of pathogen transmission used in
      epidemiological models. Some shrimp may be less aggressive feeders; therefore,
      susceptible shrimp are differentially contacting the dead infected shrimp in the
      exposure tanks, violating the random mixing assumption. Moreover, virus is
      probably not homogeneously distributed throughout an infected shrimp, suggesting
      that contacts between susceptible and infected shrimp are not equally likely to
      result in transmission.

PMID- 11463106
TI  - Phylogenetic relationships of aquatic birnaviruses based on deduced amino acid
      sequences of genome segment A cDNA.
AB  - Aquatic birnaviruses, such as infectious pancreatic necrosis virus (IPNV), cause
      serious diseases in a variety of fish species used worldwide in aquaculture and
      have also been isolated from a variety of healthy fish and shellfish species.
      These viruses exhibit a high degree of antigenic heterogeneity and variation in
      biological properties such as pathogenicity, host range, and temperature of
      replication. To better understand genetic and biological diversity among these
      viruses, the nucleotide and deduced amino acid sequences were determined from
      cDNA of the large open reading frame (ORF) of genome segment A of the 9 type
      strains of Serogroup A and 4 other representative strains of Serotype A1, the
      predominant serotype in the United States. In addition, nucleotide and deduced
      amino acid sequences were determined for the VP2 coding region of a variety of
      isolates representing 5 of the 9 serotypes. VP2 is the major outer capsid protein
      of aquatic birnaviruses. RT-PCR was used to amplify a 2904 bp cDNA fragment
      including all but a few bp of the large ORF of genome segment A or a 1611 bp
      fragment representing the entire VP2 coding region. Nucleotide and deduced amino
      acid sequences were determined from the PCR products. Pairwise comparisons were
      made among our data and 2 other aquatic birnavirus sequences previously
      published. Several hypervariable regions were identified within the large ORF.
      The most divergent pair of viruses exhibited a similarity of 80.1% in the deduced
      amino acid sequence encoded by the large ORF. Genomic relationships revealed in a
      phylogenetic tree constructed from comparison of the deduced amino acid sequences
      of the large ORF demonstrated that these viruses were clustered into several
      genogroups. Phylogenetic comparison of the deduced amino acid sequences of the
      VP2 coding region of 28 aquatic birnavirus isolates, including the type strains
      of all 9 serotypes, demonstrated 6 genogroups, some of which were comprised of
      several genotypes. The most divergent pair of viruses exhibited a similarity of
      81.2% in the deduced amino acid sequence from the VP2 coding region. In contrast
      to previous studies of much shorter genomic sequences within the C-terminus
      pVP2/NS junction coding region, these genogroups based on the entire large ORF or
      the VP2 coding region generally correlated with geographical origin and
      serological classification. Isolates from the major Canadian serotypes were more
      closely related to the European isolates than to isolates from the United States.

PMID- 11463107
TI  - Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline
      alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in
      northeastern Irian Jaya, Indonesia.
AB  - Combination therapy is one method of overcoming the global challenge of drug
      resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in
      vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone
      for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia.
      Eighty-nine patients with uncomplicated falciparum malaria were randomized to
      standard dose chloroquine (n = 30), doxycycline (100 mg every 12 hours [7 days],
      n = 20), or chloroquine with doxycycline (n = 39); corresponding numbers for
      vivax malaria (n = 63) were 23, 16, 24. Endpoints were parasite sensitivity (S)
      or resistance (RI/RII/RIII). Of the 105 evaluable patients,
      chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with
      P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured
      11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]).
      Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%])
      patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7
      51.1%]). Chloroquine/doxycycline was effective against P. falciparum but only
      modestly effective against P. vivax. These findings support the use of
      chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating
      chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in
      this setting.

PMID- 11463108
TI  - Clinical trial of beta-arteether versus quinine for the treatment of cerebral
      malaria in children in Yaounde, Cameroon.
AB  - One hundred and two children aged 0-10 years with cerebral malaria (Blantyre coma
      score of 2 or less) were randomly treated either with intramuscular arteether
      (3.2 mg/kg on Day 0, followed by 1.6 mg/kg on Days 1 to 4) or intravenous (i.v.)
      quinine dihydrochloride (20 mg of the salt/kg, followed by 10 mg of the salt/kg
      every 8 hr up to Day 6). Treatment with oral quinine sulfate (10 mg/kg every 8
      hr) was substituted for i.v. quinine when the patient was able to take oral
      medicine. All patients were followed up in the hospital for 7 days; thereafter,
      they were treated as outpatients on Days 14, 21, and 28. Mortality rate, the main
      efficacy parameter, was 11.8% lower in the arteether treatment group than in the
      quinine group (15.7% versus 27.4%); however, the difference was not significant
      (P = 0.25). Means for fever clearance time, coma resolution time, and parasite
      clearance time were similar in the 2 treatment groups (42.2 +/- 34.9 hr; 34.8 +/-
      18.8 hr, and 46.3 +/- 28.5 hr, respectively for arteether, versus 45.0 +/- 26.7
      hr; 30.3 +/- 18.9 hr, and 40.7 +/- 18.9 hr, respectively, for quinine). At 28
      days, the cure rates were 73.2% and 64.9% for the arteether and quinine treatment
      groups, respectively. Arteether is safe and therapeutically at least as effective
      as quinine for the treatment of cerebral malaria in children in Cameroon. Because
      of its ease of administration, arteether appears to be suited for use in the
      rural zones where monitoring facilities do not exist.

PMID- 11463109
TI  - A colorimetric in vitro drug sensitivity assay for Plasmodium falciparum based on
      a highly sensitive double-site lactate dehydrogenase antigen-capture enzyme
      linked immunosorbent assay.
AB  - We report a double-site enzyme-linked lactate dehydrogenase immunodetection assay
      (DELI), a highly sensitive antigen-capture enzyme-linked immunosorbent assay,
      which proved to be more sensitive for the detection of Plasmodium falciparum than
      thick blood smears, as sensitive as the polymerase chain reaction, and probably
      more reliable. This technique can help to detect infra-microscopic parasitemias
      (one parasite in 10(6)-10(8) red blood cells) from biological samples, and being
      quantitative, provide a fast substitute to thick smears for epidemiologic
      purposes. The technique can also be used to measure the in vitro drug sensitivity
      of P. falciparum with greater ease, much greater speed, and simpler equipment
      than that required for the isotopic microtest. Results obtained with four
      antimalarial drugs upon 16 strains closely paralleled those obtained by the
      isotopic assay (R = 0.95). In contrast with the latter, much lower parasite
      densities could be tested in the DELI assay (as low as 0.005%), thereby extending
      the number of isolates that can be investigated. The ease of implementation and
      low cost of the DELI-microtest may contribute to a revived interest in using in
      vitro methods to survey resistance to antimalarial drugs, so as to better predict
      future in vivo drug failures and provide public health recommendations.

PMID- 11463110
TI  - Chloroquine treatment of uncomplicated Plasmodium falciparum malaria in Mali:
      parasitologic resistance versus therapeutic efficacy.
AB  - Whether and when to replace chloroquine with other antimalarial drugs is an
      urgent public health question in much of Africa, where Plasmodium falciparum,
      which is increasingly resistant to chloroquine, continues to kill millions each
      year. Antimalarial drug efficacy has traditionally been measured as parasitologic
      resistance, but recent guidelines use both clinical and parasitologic criteria to
      monitor therapeutic efficacy. To assess the new efficacy protocol, we measured
      parasitologic and therapeutic outcomes in 514 patients treated with chloroquine
      for uncomplicated P. falciparum malaria in Mali. There was a general agreement
      between parasitologic and therapeutic outcomes at two sites, with 13-17%
      parasitologic resistance rates and 10-15% treatment failure rates. However, the
      new protocol overestimated early treatment failure rates (21-71% of cases
      classified as early treatment failure had sensitive or RI parasitologic
      responses), particularly where resistance was rare, and missed low-level
      parasitologic resistance. Modifications of the protocol for monitoring
      antimalarial therapeutic efficacy are recommended.

PMID- 11463111
TI  - A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for
      multidrug-resistant Plasmodium falciparum malaria in Thailand.
AB  - The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether
      lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were
      assessed in a randomized trial in 219 patients (> or = 12 years old) with acute,
      uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty
      four patients received artemether-lumefantrine and 55 received the standard
      treatment combination of mefloquine-artesunate. Both drugs induced rapid
      clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5%
      (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100%
      (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of
      artemether-lumefantrine was very well tolerated, with very good compliance. The
      most frequent adverse events were headache, dizziness, nausea, abdominal pain,
      dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups
      showed QTc prolongations but without any cardiac complication, and no differences
      were seen between patients with and without measurable baseline plasma levels of
      quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and
      lumefantrine were consistent with historical data for the same dose regimen, and
      were higher, particularly for lumefantrine, than those previously observed with
      the four-dose regimen, explaining the greater efficacy of the six-dose regimen in
      a drug-resistant setting. These results confirm the excellent safety and efficacy
      of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug
      resistant P. falciparum malaria.

PMID- 11463112
TI  - A field study on malaria prevalence in southeastern Laos by polymerase chain
      reaction assay.
AB  - A detection survey for malaria infection by routine microscopy and polymerase
      chain reaction (PCR) assay was conducted on 336 inhabitants of two villages in
      Khammouane Province, Lao People's Democratic Republic (Lao PDR), in July 1997.
      Malaria infection was demonstrated in 58 (17.3%) subjects by microscopy and in
      117 (34.8%) by PCR assay. Specimens positive by both methods were frequent in
      young villagers, suggesting the presence of many subclinical infections in older
      persons. The most common species of malaria parasite was Plasmodium falciparum
      (82.9%). Polymerase chain reaction assay detected mixed infections with 2-4
      species in 27 specimens (23.1%). The results demonstrate that there are many
      subclinical malaria infections with low parasite level and infection with all
      four human malaria species in Lao PDR.

PMID- 11463113
TI  - Prospective risk of morbidity in relation to malaria infection in an area of high
      endemicity of multiple species of Plasmodium.
AB  - In an area of Papua New Guinea with high prevalence of Plasmodium falciparum
      (39.6%), Plasmodium vivax (18.3%), and Plasmodium malariae (13.8%), cross
      sectional analysis found P. falciparum infection to be independent of the other
      species despite heterogeneities in transmission. Plasmodium vivax and P. malariae
      infections were negatively correlated. Plasmodium malariae infection was
      positively associated with homologous infection four months previously and with
      prior P. falciparum, but not P. vivax infection. There were no other indications
      that any Plasmodium species protected against heterologous infection. Prospective
      analysis of health-center morbidity supported the idea that P. malariae infection
      protects against disease, but indicated greater protection against non-malaria
      than P. falciparum-associated fevers. Plasmodium vivax appeared to protect
      against P. falciparum disease but not against other forms of morbidity. Covariate
      adjustment had considerable effects on estimated relationships between species,
      and confounding variables may account for many differences among reports of inter
      species interactions in human malaria.

PMID- 11463114
TI  - Short report: seroprevalence of Taenia solium cysticercosis in pigs in Bahia
      State, northeastern Brazil.
AB  - To determine the prevalence and etiologic factors of Taenia solium cysticercosis
      in pigs in the state of Bahia, northeastern Brazil, we performed serological
      surveys in Salvador, the capital of the state, and in two local towns, Santo
      Amaro and Jequie. Residents raising free-roaming pigs in the study areas were
      randomly selected. Sera were obtained from the pigs and examined by the enzyme
      linked immunoelectrotransfer blot assay (EITB). The prevalence of antibodies to
      T. solium was 4.4% (2 of 45) in Salvador, 3.2% (3 of 93) in Santo Amaro, and
      23.5% (24 of 102) in Jequie. A significantly high seroprevalence in Jequie was
      associated with poor sanitary conditions, such as an open sewer system and no
      inspection process of pork before marketing.

PMID- 11463115
TI  - The use of IS2404 restriction fragment length polymorphisms suggests the
      diversity of Mycobacterium ulcerans from different geographical areas.
AB  - Buruli ulcer, caused by Mycobacterium ulcerans, has been reported in five
      continents: Africa, Asia, Australia, and North and South America. In the present
      study, restriction fragment length polymorphism with the recently described M.
      ulcerans specific insertion sequence IS2404 as a probe, was applied to
      Mycobacterium shinshuense, Mycobacterium marinum, and 14 clinical M. ulcerans
      isolates originating from six geographic areas: Africa (n = 6), Australia (n =
      2), Mexico (n = 1), south Asia (n = 2), Asia (n = 1), and South America (n = 2).
      Using this probe, six subtypes of M. ulcerans, related to the six geographic
      origins of the isolates were distinguished, confirming that M. ulcerans can be
      divided into subgroups corresponding to different geographic variants of the same
      species.

PMID- 11463116
TI  - Tonate virus infection in French Guiana: clinical aspects and seroepidemiologic
      study.
AB  - Two recent cases of human infection with Tonate virus, one of which was a fatal
      case of encephalitis, have renewed interest in these viruses in French Guiana.
      The clinical aspects of confirmed and probable cases of infection with this virus
      indicate that it has pathogenic properties in humans similar to those of other
      viruses of the Venezuelan equine encephalitis complex. To determine the
      prevalence of antibodies to Tonate virus in the various ethnic groups and areas
      of French Guiana, 3,516 human sera were tested with a hemagglutination inhibition
      test. Of these, 11.9% were positive for the virus, but significant differences in
      seroprevalence were found by age, with an increase with age. After adjustment for
      age, significant differences were found between places of residence. The
      prevalence of antibody to Tonate virus was higher in savannah areas, especially
      in the Bas Maroni (odds ratio [OR] = 22.2, 95% confidence interval [CI] = 15.2
      32.4) and Bas Oyapock areas (OR = 13.4; 95% CI = 9.8-18.4). The ethnic
      differences observed in this study were due mainly to differences in place of
      residence, except that whites were significantly less frequently infected than
      other ethnic groups. This study indicates that Tonate virus infection is highly
      prevalent in French Guiana, especially in savannah areas.

PMID- 11463117
TI  - Case report: Acute myocardial infarction complicating a viper bite.
AB  - Myocardial infarction is a rare complication of snakebite. The present report
      describes a 40-year-old Jordanian farmer who developed an acute myocardial
      infarction several hours after a snakebite. The diagnosis of myocardial
      infarction was confirmed by a typical history of retrosternal chest pain,
      characteristic electrocardiographic changes, and elevated serum creatinine kinase
      (MB-CK). The patient had no risk factors for coronary artery disease and the
      coronary arteries were normal on cardiac catheterization. The possible mechanisms
      leading to myocardial infarction following snakebite are discussed.

PMID- 11463118
TI  - Specific heterologous F(ab')2 antibodies revert blood incoagulability resulting
      from envenoming by Lonomia obliqua caterpillars.
AB  - Contact with Lonomia obliqua caterpillars results in a bleeding syndrome
      characterized by hemorrhage and blood coagulation disturbances. Conventional
      therapy using antifibrinolytics or cryoprecipitates has been unable to treat
      pathophysiologic alterations. As antivenoms are effective therapy for treatment
      of victims of venomous animals, a process of manufacturing a specific antilonomic
      serum by immunizing horses with Lonomia caterpillar bristle extracts (LBE) was
      developed. Lonomia caterpillar bristle extracts exhibited several protein bands
      on SDS-PAGE, induced blood coagulation abnormalities and lethality in mice, and
      stimulated specific antibody production in horses. Sera obtained from immunized
      horses were rich in anti-LBE specific antibodies distributed among the horse IgG
      isotypes. These antibodies had the ability to recognize various LBE antigens as
      well as to neutralize their coagulopathy-inducing activity. The antivenom
      manufactured by the developed process was composed of purified and sterilized
      F(ab')2 with ED50 = 38.61 microl, potency = 0.29 mg/ml, and 95% confidence limit
      of potency 0.20-1.36.

PMID- 11463119
TI  - Automated detection of malaria pigment in white blood cells for the diagnosis of
      malaria in Portugal.
AB  - A novel automated method (Cell-Dyn 3500) allows malaria diagnosis by detecting
      malaria pigment in white blood cells during routine full blood counts. In
      Portugal, 174 samples from 148 patients who presented to the emergency department
      were analyzed. Compared with microscopy the sensitivity was 95% and the
      specificity was 88%. In 5 cases, false-positive Cell-Dyn 3500 results were from
      patients who had a recent history of treated malaria, indicating that the method
      may remain positive during convalescence. Six patients were diagnosed due to the
      changes observed with the automated method only, because clinicians had not
      requested malaria smears. This instrument appears to provide a promising method
      for the diagnosis of malaria, especially where automated full blood counts are
      routine in the work-up of febrile patients.

PMID- 11463120
TI  - Multiplex polymerase chain reaction amplification and differentiation of
      Entamoeba histolytica and Entamoeba dispar DNA from stool samples.
AB  - Due to the clinical importance of differentiating the two species of the
      Entamoeba histolytica/Entamoeba dispar complex, we developed a multiplex
      polymerase chain reaction (PCR) method that overcomes time-consuming and
      laborious procedures. We report here a DNA extraction protocol using non-fixed
      stool samples that avoid long lysis-incubation periods through the combined use
      of zirconium beads and a lysis-supporting buffer. We characterized 49 of 52 stool
      specimens from Cuban patients with amoebiosis. Among them, 36 (75.5%) were
      infected only with E. dispar (the nonpathogenic species), while 13 (24.5%)
      displayed a mixed infection with both E. dispar and E. histolytica. The multiplex
      PCR protocol showed a specificity of 1.00 and a sensitivity of 0.94. Furthermore,
      the entire procedure can be performed in one day. This approach is therefore
      reliable and applicable in the field for epidemiologic studies.

PMID- 11463121
TI  - Pathogenic aspects of pyogenic liver abscess associated with experimental
      schistosomiasis.
AB  - Schistosomiasis mansoni infection that occurs concurrently with Staphylococcus
      aureus bacteremia favors the formation of pyogenic liver abscess. The present
      experimental study in mice evaluated the following aspects of the relationship
      between infection with Schistosoma mansoni and liver abscess caused by S. aureus:
      a) the role of the eggs of S. mansoni in the genesis of the abscesses; b) the
      influence of different phases of schistosomiasis in the development of liver
      abscesses; and c) the effect of the treatment of schistosomiasis on the
      development of the abscesses. Macroscopic and histopathological study showed
      multiple liver abscesses around granulomas of S. mansoni in the acute and chronic
      phases of schistosomiasis. Treatment of acute schistosomiasis before
      experimentally-induced bacteremia did not prevent the formation of liver abscess.
      The study findings indicate that granulomas around S. mansoni eggs and worms
      lodged in the liver provide a focus and substrate for pyogenic abscesses caused
      by S. aureus.

PMID- 11463122
TI  - Increased multiplicity of Plasmodium falciparum infections and skewed
      distribution of individual msp1 and msp2 alleles during pregnancy in Ndiop, a
      Senegalese village with seasonal, mesoendemic malaria.
AB  - Pregnancy is associated with a greater susceptibility to Plasmodium falciparum
      infections, which may result in serious complications affecting both the mother
      and the fetus. To compare allelic diversity and multiplicity of infection in the
      same women during and outside pregnancy, we conducted a retrospective analysis of
      the monthly fingerprick blood samples collected during a longitudinal survey
      conducted in Ndiop, a Senegalese village with mesoendemic malaria. Merozoite
      surface protein-1 (msp1) block 2 and merozoite surface protein-2 (msp2) genotypes
      were determined for 308 blood samples collected from 20 women. Pregnancy was
      associated with a significantly higher prevalence of P. falciparum infection,
      higher parasite densities, and a higher multiplicity of infection. The highest
      multiplicity of infection was observed in the youngest pregnant women. Because of
      co-linearity, it was not possible to dissociate the impact of age from that of
      parity on multiplicity of infection. Some individual msp1 and msp2 alleles showed
      a highly skewed pregnancy-associated distribution. These results indicate that
      pregnancy is associated with increased permissiveness to a large number of
      clones, as well as with infection by specific genotypes.

PMID- 11463123
TI  - Sylvatic transmission of arboviruses among Bornean orangutans.
AB  - Wild populations of nonhuman primates live in regions of sylvatic arbovirus
      transmission. To assess the status of arbovirus transmission in Bornean forests
      and the susceptibility of wild orangutans to arboviral infection, blood samples
      of wild orangutans, semi-captive orangutans, and humans were examined. Samples
      were tested by plaque reduction neutralization test for antibodies to viruses
      representing three families (Flaviviridae, Alphaviridae, and Bunyaviridae),
      including dengue-2, Japanese encephalitis, Zika, Langat, Tembusu, Sindbis,
      Chikungunya, and Batai viruses. Both wild and semi-captive orangutan groups as
      well as local human populations showed serologic evidence of arbovirus infection.
      The presence of neutralizing antibodies among wild orangutans strongly suggests
      the existence of sylvatic cycles for dengue, Japanese encephalitis, and sindbis
      viruses in North Borneo. The present study demonstrates that orangutans are
      susceptible to arboviralinfections in the wild, although the impact of arboviral
      infections on this endangered ape remain unknown.

PMID- 11463124
TI  - Case report: Unusual location of Dirofilaria immitis in a 28-year-old man
      necessitates orchiectomy.
AB  - The fourth case of zoonotic Dirofilaria immitis infection in a California
      resident is reported. This case was unique in that it involved the spermatic
      cord, produced significant symptoms, and upon physical examination was suspected
      of being an incarcerated inguinal hernia. At surgery frozen sections were
      inconclusive regarding neoplasia and cord involvement precluded removal of the
      mass without orchiectomy, which was done. Histopathology revealed a well
      preserved immature male D. immitis, the canine heartworm, in a branch of the
      spermatic artery. The morphological identification of the worm was confirmed by
      polymerase chain reaction (PCR) studies. This case illustrates that D. immitis
      infections can complicate differential diagnosis of extrapulmonary lesions and
      suggests that the public health significance of this vector-borne filarial worm
      needs to be evaluated through appropriate epidemiological studies in enzootic
      areas.

PMID- 11463125
TI  - Neuroprotection for ischaemic stroke: an unattainable goal?
AB  - Neuroprotective therapies for acute ischaemic stroke have yet to be realised
      despite the determined efforts of basic science and clinical investigators.
      Progressive elucidation of the complex pathophysiology involved in the ischaemic
      cascade has led to the development of numerous candidate interventions.
      Preliminary efficacy in animal models has repeatedly resulted in frustration
      after extensive clinical testing. Failure in the translation of results from
      animal models to humans implicates potential limitations of the current drug
      development process. Reflection on prior studies suggests possible flaws at
      several stages. Incorporation of standardised guidelines for preclinical testing
      of putative neuroprotective therapies and modification of clinical trial design,
      methodology and reporting may improve chances for success. The future of
      neuroprotection for stroke remains bright in spite of previous disappointments.

PMID- 11463126
TI  - Psychotic and mood disorders associated with the perimenopausal period:
      epidemiology, aetiology and management.
AB  - Contrary to widely held beliefs, menopause is not associated with an increase in
      psychiatric illness. Although just prior to menopause there is a slight increase
      in minor psychological symptoms, prevalence rates of depression fall
      postmenopause. Hypotheses for the occurrence of depression in some perimenopausal
      women include: a pre-existing sensitivity to the change in the gonadal hormones
      leading to decreases in neural transmitters; reactions to the physiological
      changes associated with menopause such as night sweats, or the influence of a
      multitude of negative attitudes and expectations concerning menopause. The loss
      of the protective effects of estrogen may be related to the slight increase in
      the incidence of schizophrenia in women at menopause. The role of hormone
      replacement therapy (HRT) in treating psychiatric symptoms remains poorly
      understood. In nondepressed women, HRT may improve well-being either as a direct
      effect or as a consequence of reduced physical symptoms and fear of aging. In
      women with moderate to severe depressions, HRT alone does not appear to be
      beneficial. HRT may have some beneficial effects on short term memory. More
      research is needed to assess the possible role of HRT in augmenting the effects
      of antidepressant and antipsychotic medications.

PMID- 11463127
TI  - Kleptomania: diagnosis and treatment options.
AB  - Kleptomania--the inability to resist the impulse to steal objects, not for
      personal use or monetary gain--is currently classified in psychiatric
      nomenclature as an impulse control disorder. However, some of the principle
      features of the disorder, which include repetitive intrusion thoughts, inability
      to resist the compulsion to perform the thievery and the relief of tension
      following the act, suggest that kleptomania may constitute an obsessive
      compulsive spectrum disorder. Kleptomania is commonly under-diagnosed and is
      often accompanied by other psychiatric conditions, most notably affective,
      anxiety and eating disorders, and alcohol and substance abuse. Individuals with
      the disorder are usually referred for treatment due to the comorbid psychiatric
      complaints rather than kleptomanic behaviour per se. Over the past century there
      has been a shift from psychotherapeutic to psychopharmacological interventions
      for kleptomania. Pharmacological management using selective serotonin (5
      hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) and other antidepressants,
      mood stabilisers and opioid receptor antagonists, as adjuvants to cognitive
      behavioural therapy, has produced promising results.

PMID- 11463128
TI  - Occupational exposure to volatile anaesthetics: epidemiology and approaches to
      reducing the problem.
AB  - Long term occupational exposure to trace concentrations of volatile anaesthetics
      is thought to have adverse effects on the health of exposed personnel. In
      contrast with halothane--an agent likely to cause mutagenic effects and proven to
      be teratogenic--isoflurane and enflurane have not so far been proved to have
      adverse effects on the health of personnel exposed long term. Data on the newer
      agents sevoflurane and desflurane are limited. Since possible health hazards from
      long term exposure to inhalational anaesthetics cannot yet be definitively
      excluded, many Western countries have established limits for exposure. These
      usually range from 2 to 10 ppm as a time-weighted average over the time of
      exposure. A number of investigations have demonstrated that, in operating
      theatres with modern climate control and waste anaesthetic gas scavenging
      systems, occupational exposure is unlikely to exceed threshold limits. However,
      occupational exposure from the use of volatile agents in operating theatres with
      poor air control--especially during bronchoscopy procedures in paediatric
      patients--remains a source of concern. This also holds true for both
      postanaesthesia care units (PACU) and intensive care units (ICU) lacking proper
      air conditioning and waste gas scavengers. To minimise occupational exposure to
      volatile anaesthetics, all measures must be taken to provide climate control and
      properly working scavenging devices, and ensure sufficient personal skill of the
      anaesthetist, e.g. during inhalational mask induction. Furthermore, low-flow
      anaesthesia should be used whenever possible. The sole use of intravenous drugs
      such as propofol instead of volatile agents, were this possible, would eliminate
      occupational exposure, but may result in environmental pollution by toxic
      metabolites (e.g. phenol).

PMID- 11463129
TI  - Visual field defects with vigabatrin: epidemiology and therapeutic implications.
AB  - Vigabatrin is an antiepileptic drug (AED) that acts as a selective irreversible
      inhibitor of gamma-aminobutyric acid (GABA) transaminase. In 1997, 3 cases of
      severe symptomatic and persistent visual field constriction associated with
      vigabatrin treatment were described. During 1997 to 1998, similar concentric
      visual field constrictions were described in patients with drug-resistant
      epilepsy who were receiving vigabatrin concurrently with other AEDs. However, a
      study of patients treated with vigabatrin monotherapy alone showed that there was
      a causal relationship between vigabatrin treatment and the specific bilateral
      concentric visual field constriction. The Marketing Authorisation Holders survey
      (involving 335 vigabatrin recipients aged >14 years) indicated that 31% of
      patients [95% confidence interval (CI) 26 to 36%] had a visual field defect
      attributable to vigabatrin, compared with a 0% incidence of visual field defects
      (upper 95% CI 3%) in an unexposed control group. Other studies in adults have
      given similar overall prevalences, with a total of 169 of 528 patients diagnosed
      with vigabatrin-associated field defects (32%, 95% CI 28 to 36%). Male gender
      seems to be associated with an increase in the relative risk of visual field loss
      of approximately 2-fold. The pattern of defect is typically a bilateral, absolute
      concentric constriction of the visual field, the severity of which varies from
      mild to severe. Data gathered so far suggest that the cumulative incidence
      increases rapidly during the first 2 years of treatment and within the first 2 kg
      of vigabatrin intake, stabilising at 3 years and after a total vigabatrin dose of
      3 kg. The prevalence of vigabatrin-associated field defects seems to be lower in
      children, but there are also methodological problems and greater variability in
      the assessment of visual fields in children. There is particular concern that the
      increased risk of the visual field defects will outweigh the benefit of the drug
      in patients who could be controlled with other AEDs. Vigabatrin should currently
      be used only in combination with other AEDs for patients with resistant partial
      epilepsy when all other appropriate drug combinations have proved inadequate or
      have not been tolerated. Regular visual field testing should be performed before
      the start of treatment and at regular intervals during treatment. Patients with
      pre-existent visual field defects due to other causes should not be treated with
      vigabatrin. Currently, the benefits of treating infantile spasms with vigabatrin
      monotherapy seem to outweigh the risks, but further prospective studies and
      follow-up of children receiving treatment are needed to evaluate the place of
      vigabatrin in this indication.

PMID- 11463130
TI  - Tianeptine: a review of its use in depressive disorders.
AB  - Tianeptine is an antidepressant agent with a novel neurochemical profile. It
      increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast
      with most antidepressant agents) and reduces stress-induced atrophy of neuronal
      dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in
      contrast with most tricyclic antidepressant agents, tianeptine does not appear to
      be associated with adverse cognitive, psychomotor, sleep, cardiovascular or
      bodyweight effects and has a low propensity for abuse. Tianeptine has a
      comparatively favourable pharmacokinetic profile. It is not subject to first-pass
      hepatic metabolism, has high bioavailability and limited distribution, and is
      rapidly eliminated. While this offers advantages for tianeptine over the
      tricyclic antidepressant agents in terms of dose titration, treatment changes and
      potential drug interactions, its rapid elimination makes adherence to dosage
      schedules more important. Tianeptine differs from most antidepressants in that it
      is not primarily metabolised by the hepatic cytochrome P450 system, indicating
      less likelihood of drug-drug interactions; this is of particular interest for
      elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been
      investigated in patients with major depression, depressed bipolar disorder,
      dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to
      several classical antidepressant agents (amitriptyline, clomipramine, imipramine,
      mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and
      sertraline. Comparison with maprotiline indicated superior efficacy for
      tianeptine but dothiepin appeared superior in another study. Extended treatment
      with tianeptine decreases the incidence of relapse/recurrence of depression.
      Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline,
      clomipramine and mianserin and more effective than maprotiline in improving
      associated anxiety in patients with depressive disorders. Depression and anxiety
      symptoms in alcohol dependant patients also respond well to tianeptine. The
      adverse effects associated with tianeptine are similar in many respects to those
      of the SSRIs and minimal in comparison with the tricyclic antidepressants. The
      most common adverse effects are nausea, constipation, abdominal pain, headache,
      dizziness and changes in dreaming. Anticholinergic effects occur less often with
      tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be
      decreased in elderly patients and those with severe renal failure, but adjustment
      is not necessary in patients with alcoholism or hepatic impairment, or those
      undergoing haemodialysis. CONCLUSIONS: The antidepressant efficacy and favourable
      tolerability and pharmacokinetic profiles of tianeptine in patients with
      depression, including those with associated anxiety, have been proven; the data
      indicate that it may have additional potential in specific subgroups of depressed
      patients such as the elderly and those with chronic alcoholism.

PMID- 11463131
TI  - Glucose for smoking cessation: does it have a role?
AB  - Nicotine replacement therapies and amfebutamone (bupropion) have both been shown
      to aid smoking cessation. However, even with the best support most attempts to
      stop smoking fail, and many smokers prefer not to use medications in their quit
      attempts. Oral dextrose (glucose) has been proposed as a possible aid to smoking
      cessation which would be very inexpensive and might be used by some smokers as
      well as or instead of medications. It is hypothesised that single doses of
      nicotine relieve hunger in smokers so that over time smokers therefore come, in
      certain situations, to interpret sensations associated with hunger as craving for
      a cigarette. Adaptation to long term nicotine intake leads to exacerbation of
      these sensations during periods of abstinence. Chewing dextrose tablets results
      in a rapid increase in blood glucose levels that would be expected to yield a
      small reduction in these sensations which might then translate into a reduction
      in craving. An intervention that reduced craving might help smokers to maintain
      abstinence. Placebo-controlled studies have provided some support for the
      hypothesis that chewing glucose tablets can reduce desire to smoke during
      abstinence, and the one adequately powered study carried out so far found that
      glucose tablets increased 1-month abstinence rates significantly compared with a
      placebo. Definitive trials are now required but, given their low cost, glucose
      tablets may be a useful aid for some smokers.

PMID- 11463132
TI  - Sleep disorders in patients with Parkinson's disease: epidemiology and
      management.
AB  - Patients with Parkinson's disease can experience a number of sleep disorders,
      including insomnia, parasomnias and daytime somnolence [specifically, excessive
      daytime sleepiness (EDS) and sleep attacks]. Insomnia is a frequent and important
      complaint of patients with the disease. Both the pathology of Parkinson's disease
      and dopaminergic drugs may contribute to the much higher than expected frequency
      of sleep fragmentation and disrupted sleep among these patients. In addition,
      coexisting depression seems to be a major and frequent risk factor for insomnia
      in Parkinson's disease. After recognising a sleep problem, the first step in
      management is to examine and diagnose the type of insomnia and possible medical
      or psychological factors that may disturb nocturnal sleep. The next step is to
      give the patient appropriate advice on sleep hygiene. Increasing the dosage of
      dopaminergic drug treatment will often increase sleep disruption and should be
      avoided unless the patient's sleep is primarily disturbed by the motor
      manifestations of parkinsonism during the night. Depression should be looked for
      and if appropriate be treated in any patients with insomnia. If it becomes
      necessary to treat the patient with an hypnosedative agent, it is important to
      use a drug with a short half-life and that manifests as few adverse effects as
      possible the next morning. Up-to-date guidelines for the use of hypnosedatives
      should be followed. Patients with Parkinson's disease experience a wide range of
      parasomnias. The majority of behaviours may be related to rapid eye movement
      (REM) sleep behaviour disorder (RBD) or to a spectrum of symptoms ranging from
      vivid dreaming to psychosis. RBD is effectively treated with clonazepam. In
      addition, the atypical antipsychotics have given physicians new and better
      treatment options for psychotic symptoms in individuals with Parkinson's disease.
      EDS is common in Parkinson's disease, while sleep attacks seem to be rare
      manifestations of the disease or its treatment. Significant EDS is found in 15%
      of patients with Parkinson's disease compared with in 1% of healthy elderly
      people. Sleep attacks are observed in patients treated with all dopaminergic
      medications but have recently been brought to prominence because of their
      association with the newer dopamine agonists ropinirole and pramipexole. Patients
      with Parkinson's disease should be informed about the possibility of developing
      sleep problems during the day when prescribed new drugs. Appropriate actions with
      regard to driving must be taken if significant and persistent daytime somnolence
      or sleep attacks appear.

PMID- 11463133
TI  - The role of central serotonergic dysfunction in the aetiology of premenstrual
      dysphoric disorder: therapeutic implications.
AB  - Premenstrual dysphoric disorder (PMDD), as defined in DSM-IV, is a mood disorder.
      One of the leading theories for the pathogenesis of mood disorders is dysfunction
      of the serotonergic system. An increasing database suggests that serotonergic
      dysfunction also characterises PMDD. Evidence that treatments which enhance
      serotonergic function are beneficial in reducing the symptoms of PMDD support
      this hypothesis. Indeed, most of the evidence from baseline studies suggests
      predominantly a serotonergic rather than a noradrenergic or dopaminergic
      dysfunction. Challenge studies further support this hypothesis. These findings of
      neurotransmitter dysfunction are more consistent than those of other
      neuroendocrine abnormalities for example. Based on treatment studies, a selective
      serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, fluoxetine, has been
      approved for use in PMDD by the US Food and Drug Administration.

PMID- 11463134
TI  - Oxidative damage and schizophrenia: an overview of the evidence and its
      therapeutic implications.
AB  - Free radicals are highly reactive chemical species generated during normal
      metabolic processes. which in excess can lead to membrane damage. Elaborate
      antioxidant defence systems exist to protect against oxidative stress. There is
      accumulating evidence of altered antioxidant capacity in schizophrenia. Membrane
      dysfunction can be secondary to free radical-mediated pathology, and may
      contribute to specific aspects of schizophrenic symptomatology and complications
      of its treatment. Specifically, free radical-mediated abnormalities may
      contribute to the development of a number of clinically significant consequences,
      including prominent negative symptoms, tardive dyskinesia, neurological 'soft'
      signs and parkinsonian symptoms. Our previous results showing altered membrane
      dynamics and antioxidant enzyme activities in schizophrenia, and findings from
      other investigators, are consistent with the notion of free radical-mediated
      neurotoxicity in schizophrenia. These findings provide a theoretical basis from
      which the development of novel therapeutic strategies such as fatty acid and
      antioxidant supplementation can occur in the future.

PMID- 11463136
TI  - Perospirone.
AB  - Perospirone is an atypical antipsychotic agent for the treatment of
      schizophrenia. Its primary mode of action is through antagonism of serotonin 5
      HT2A and dopamine D2 receptors. An 8-week course of oral perospirone 8 to 48
      mg/day displayed efficacy in up to 75% of patients with schizophrenia
      participating in phase II and phase III trials. The onset of action of the drug
      was about 2 weeks. Perospirone was effective against positive, negative and
      general symptoms in patients with schizophrenia, as assessed with standard rating
      scales (Brief Psychiatric Rating Scale, Positive and Negative Symptom Scale).
      Compared with haloperidol 2 to 12 mg/day, perospirone 8 to 48 mg/day was
      significantly more effective against negative symptoms and tended to be more
      effective against general symptoms and most positive symptoms in a trial in 145
      patients with schizophrenia. Perospirone had efficacy similar to that of
      mosapramine 50 to 300 mg/day in a comparative phase III trial in 159 patients.
      Extrapyramidal symptoms (EPS) tended to occur less often and were generally
      milder with perospirone than with haloperidol or mosapramine.

PMID- 11463135
TI  - Circadian rhythm sleep disorders: pathophysiology and potential approaches to
      management.
AB  - An intrinsic body clock residing in the suprachiasmatic nucleus (SCN) within the
      brain regulates a complex series of rhythms in humans, including
      sleep/wakefulness. The individual period of the endogenous clock is usually >24
      hours and is normally entrained to match the environmental rhythm. Misalignment
      of the circadian clock with the environmental cycle may result in sleep
      disorders. Among these are chronic insomnias associated with an endogenous clock
      which runs slower or faster than the norm [delayed (DSPS) or advanced (ASPS)
      sleep phase syndrome, or irregular sleep-wake cycle], periodic insomnias due to
      disturbances in light perception (non-24-hour sleep-wake syndrome and sleep
      disturbances in blind individuals) and temporary insomnias due to social
      circumstances (jet lag and shift-work sleep disorder). Synthesis of melatonin (N
      acetyl-5-methoxytryptamine) within the pineal gland is induced at night, directly
      regulated by the SCN. Melatonin can relay time-of-day information (signal of
      darkness) to various organs, including the SCN itself. The phase-shifting effects
      of melatonin are essentially opposite to those of light. In addition, melatonin
      facilitates sleep in humans. In the absence of a light-dark cycle, the timing of
      the circadian clock, including the timing of melatonin production in the pineal
      gland, may to some extent be adjusted with properly timed physical exercise.
      Bright light exposure has been demonstrated as an effective treatment for
      circadian rhythm sleep disorders. Under conditions of entrainment to the 24-hour
      cycle, bright light in the early morning and avoidance of light in the evening
      should produce a phase advance (for treatment of DSPS), whereas bright light in
      the evening may be effective in delaying the clock (ASPS). Melatonin, given
      several hours before its endogenous peak at night, effectively advances sleep
      time in DSPS and adjusts the sleep-wake cycle to 24 hours in blind individuals.
      In some blind individuals, melatonin appears to fully entrain the clock.
      Melatonin and light, when properly timed, may also alleviate jet lag. Because of
      its sleep-promoting effect, melatonin may improve sleep in night-shift workers
      trying to sleep during the daytime. Melatonin replacement therapy may also
      provide a rational approach to the treatment of age-related insomnia in the
      elderly. However, there is currently no melatonin formulation approved for
      clinical use, neither are there consensus protocols for light or melatonin
      therapies. The use of bright light or melatonin for circadian rhythm sleep
      disorders is thus considered exploratory at this stage.

PMID- 11463137
TI  - The conjoined twins of Lowen.
AB  - This paper discusses an unusual etching of unlike-sex conjoined twins of the
      syncephalus type dated 1547. The authenticity of the case is discussed in terms
      of the biological plausibility of such twins and in the light of mediaeval
      understanding of the twinning process. Unlike-sex syncephalic twins may occur as
      a result of dispermic fertilisation, or be an erroneous depiction of an
      asymmetrical anomaly of the external genitalia of a like-sex pair, mimicking the
      genitals of the other sex. On the other hand, the Lowen etching conforms with
      mediaeval beliefs that conjoined twins are divine punishment and therefore were
      used for ecclesiastical and perhaps commercial purposes. The historical context
      of the drawing, in which the relation between religion, media, and medicine
      satisfied the eagerness of the public for curios of Nature, is no longer valid.
      Thus the Lowen etching opens a window to the past from which modern medicine can
      be appreciated.

PMID- 11463138
TI  - Seasonal variation of livebirths, stillbirths, extramarital births and twin
      maternities in Switzerland.
AB  - A study was made of the seasonal variation in all births, and births according to
      marital status, multiplicity and birth status (live and still) in Switzerland
      recorded between 1876 and 1990. To obtain seasonal variation in as pure as
      possible form, our analyses are based on rates. When comparing the seasonality in
      data sets showing markedly different levels, standardised indices were used.
      Assuming the length of pregnancies with twins to be about one month shorter than
      for pregnancies with singletons, lagged twinning rates were calculated but, in
      comparison with actual twinning rates, the general seasonal variation remained.
      Therefore, this study was based on actual twinning rates. A monotonic increase in
      the amplitude of the seasonal variation in general births was noted for the
      period 1876-1930, with strong seasonal variation holding for 1921-1980. After
      that, a marked decline in the amplitude can be observed. Seasonality of both all
      births and twin maternities showed very similar pattern for the periods 1876-1930
      and 1969-1990, with maxima in the spring (March-May) and troughs in late autumn
      (October-December). Twin maternities showed a strong seasonality for the period
      1876-1930, being about 20% higher in March than in October. The twinning rate in
      the period 1876-1930 was about 2.6 per thousand units higher than in the period
      1969-90. For twin maternities there was also a stronger seasonal variation during
      the earlier period than during the later one. The pattern of the seasonal
      variation for extramarital births, showing a maximum in February (conceptions in
      May-June) and a minimum in August (conceptions in November-December) with a
      difference of no less than 24% was more marked than for the marital births. It
      seems likely that this seasonality of extra-marital maternities was due mainly to
      seasonal variation of coital rates and multiple ovulation in the early summer
      months coinciding with optima of light, temperature and food supply. A strong
      reduction in the rate of stillbirths (gestational age more than 29 weeks) was
      observed during the twentieth century. The stillbirth rate declined from about 40
      per 1000 in the 1870s to fewer than 5 per 1000 in the 1980s. Irrespective of this
      strong decline in the stillbirth rate, the same seasonal rhythm was noticed
      throughout the period with high stillbirth rates among births around March and
      low rates during the summer and autumn.

PMID- 11463139
TI  - Establishing a twin register in Sri Lanka.
AB  - Nearly all twin registers are based in developed countries and there is no twin
      register in the developing world. Our objectives were to initiate the process of
      establishing a nationwide twin register in Sri Lanka by starting a volunteer
      register first and working towards a population-based register. Regular newspaper
      advertisements, feature articles, radio talks, and television programmes were
      used to publicise a competition for twins, their parents/relatives and friends
      requesting them to participate by sending in details of twins. The competition
      ran from 28 March 1997 for a period of 3 months. It offered prizes for three
      winners selected by drawing lots. Advertisements highlighted the objective of the
      competition as establishing a twin register for future research and emphasised
      that informed consent would be obtained for individual research projects. Those
      who registered comprise 4602 twin pairs (same sex: male--1564, female--1885;
      different sex--1153), 80 sets of triplets (same sex: male--17, female--31;
      different sex--42) and two sets of quadruplets (different sex). The oldest twins,
      triplets, quadruplets are 85, 46, and 5 years old, respectively; 88.0% of twins
      are less than 30 years old. Although others have previously used media publicity
      to enrol twins in twin registers, we believe this to be the first time that twins
      have been enrolled through competition. We have more young twins, and our gender
      and zygosity proportions after applying Weinburg's rule do not match the
      proportions expected from a volunteer twin sample. Establishing a twin register
      for research purposes has proved possible in a developing country.

PMID- 11463140
TI  - Cross-cultural adaptation and preliminary validation of a zygosity determination
      questionnaire for twins in Sri Lanka.
AB  - We report the process of adaptation into Sinhala of a questionnaire given to
      mothers of twins to determine zygosity. Adaptation and validation was carried out
      in three stages. Firstly, we used a nominal group to translate the English
      version and to assess the extent of agreement (consensus measurement) on the
      appropriateness of the translation and resolve disagreement (consensus
      development). Secondly we used a qualitative interview with 25 mothers of twins.
      The three main stems of the translated questionnaire were used as a semi
      structured interview, and the responses noted verbatim. These were categorised
      and analysed, and the translated full questionnaire was then presented as closed
      questions with fixed choice responses. The categorised responses generated during
      the qualitative interview were compared with the responses to the fixed choices
      in the full questionnaire. The third stage was the appraisal of the questionnaire
      by 17 bilingual parents of twins. The source and translated version of the
      questionnaire were given to them at least 3 days apart. The responses were rated
      and the total scores were computed to determine the zygosity. This step was
      carried out to measure the validity and reliability of the Sinhala version. A
      perfect correlation between the original and adapted version was obtained, with a
      kappa of 1. The results suggest that the Sinhala version of the questionnaire is
      conceptually equivalent to the original questionnaire. Comparison of the zygosity
      determination by using this adapted questionnaire with results from analysis of
      genetic markers on Sri Lankan twins is needed for final validation of the
      translated questionnaire.

PMID- 11463141
TI  - Cervical length as a predictor of pre-term birth in twin gestations.
AB  - The aim of this study was to determine the predictive value of cervical length as
      a risk factor for spontaneous pre-term birth in twin gestations. A retrospective
      chart review was carried out on patients with twin pregnancies referred to our
      multiples' clinic. Cervical length was measured by transvaginal ultrasonography.
      Patients with an indicated pre-term delivery or intervention were excluded from
      the analysis. Outcomes included preterm delivery < 28 and < 35 weeks gestation.
      After extracting the data, 2 x 4 tables were constructed. Likelihood ratios were
      then generated for cervical lengths < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm,
      and > 3.0 cm. Because of the limited number of measurements taken < 25 weeks
      gestation, we elected to collapse the tables, thereby achieving more meaningful
      results. For measurements taken before 30 weeks gestation, a shorter cervix did
      predict delivery < 28 weeks gestation (likelihood ratios for cervical lengths <
      or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 4.43, 1.94, 0.97,
      and 1.02, respectively). The probability of preterm delivery < 35 weeks gestation
      increased with decreasing cervical length (likelihood ratios for cervical length
      < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 2.58, 1.66, 1.38,
      and 0.81, respectively). A shorter cervix measured before 30 weeks gestation was
      a stronger predictor of preterm delivery < 28 weeks compared to < 35 weeks
      gestation. Cervical length was not predictive of preterm delivery if measured
      after 30 weeks. Cervical length is predictive of preterm delivery < 28 weeks and
      < 35 weeks gestation when measured before 30 weeks gestation. No trend was seen
      when measured after 30 weeks gestation. A prospective study is currently underway
      to confirm these results.

PMID- 11463142
TI  - Assisted reproductive technologies and monozygous twins: implications for future
      study and clinical practice.
AB  - That the zona pellucida (ZP) plays a prominent role in the physiology of some
      human twinning is an attractive, albeit incompletely proven, medical hypothesis.
      Indeed, an association has been proposed between manipulation of the ZP and/or
      native ZP microarchitecture and monozygotic (MZ) twins. Ovulation induction also
      has been theoretically linked to in vivo ZP alterations facilitating MZ twin
      development. In vitro fertilization (IVF) relies on necessary (and, in some cases
      extended) embryo culture techniques potentially creating subtle ZP changes and
      subsequent MZ twinning. With growing experience in the assisted reproductive
      technologies and particularly IVF, some preliminary reports have noted an
      increased frequency of MZ twins after procedures that artificially breach the ZP
      (i.e., intracytoplasmic sperm injection [ICSI], or 'assisted hatching'). Such ZP
      manipulations ostensibly enhance oocyte fertilization or facilitate blastocyst
      hatching, thus improving pregnancy rates for couples undergoing fertility
      treatment. Evidence exists both to challenge and support the connection between
      these phenomena and MZ twins. This report outlines the fundamental embryological
      processes believed responsible for these conflicting observations; the current
      literature on the subject of human ZP micro-manipulation and MZ twins is also
      discussed.

PMID- 11463143
TI  - Parent ratings of temperament in twins: explaining the 'too low' DZ correlations.
AB  - Twin studies of child temperament using objective measures consistently suggest
      moderate heritability for most dimensions. However, parent rating measures
      produce unusual patterns of results. Intraclass correlations for identical (MZ)
      twins are typically high, whereas fraternal (DZ) twin intraclass correlations are
      much lower than would be predicted from an additive genetic model. The 'too low'
      DZ correlations can be explained by parent-rating biases that either exaggerate
      the differences between DZ twins (contrast effects) or that inflate the
      similarity of MZ twins (assimilation effects), or by the presence of non-additive
      genetic variance. To evaluate the three possible explanations, we used model
      fitting procedures applied to parent-rating data averaged across 14, 20, 24, and
      36 months of age in a sample of 196 twin pairs participating in the MacArthur
      Longitudinal Twin Study. The data were best described by a model that included
      contrast effects. Implications for non-twin research are discussed.

PMID- 11463144
TI  - Maternal behavior toward premature twins: implications for development.
AB  - Assisted reproductive techniques and fertility enhancing therapies have increased
      multiple births and, therefore, the risk of prematurity and its developmental
      consequences. Parent intervention is an effective source of compensation for the
      cognitive effects of prematurity. We hypothesized that relative to parents of
      preterm singletons, parents of preterm twins are less able to provide such
      enhancing care, resulting in a developmental disadvantage for preterm twins.
      Maternal-infant interactions of premature singletons (n = 22; birth weight = 1668
      +/- 350 g, gestational age = 32.3 +/- 2.1 weeks) and premature twins (n = 8;
      birth weight = 1618 +/- 249 g; gestational age = 32.0 +/- 2.6 weeks) with
      comparable demographic and medical status were observed at home at 1 and 8 months
      corrected age using a 30 min checklist of developmentally facilitative behavior.
      Mental (MDI) and psychomotor (PDI) indices of the Bayley Scales of Infant
      Development and Caldwell Home Observations for Measurement of the Environment
      (HOME) inventories were administered (18 months corrected age). Compared with
      mothers of premature singletons, mothers of premature twins exhibited fewer
      initiatives (P < 0.001) and responses (P < 0.01) and were less responsive to
      positive signals (P < 0.01) and crying (P < 0.01). Unprompted by the infant, twin
      mothers lifted or held (P < 0.05), touched (P < 0.01), patted (P < 0.05) or
      talked (P < 0.01) less. Singleton MDIs surpassed twins (119.4 +/- 7.7 vs 103.6 +/
      7.7; P < 0.01). Maternal verbal behavior and the acceptance of child factor
      (HOME), both favoring singletons, correlated with MDI (R-square = 0.46, P <
      0.0002). Mothers of premature twins exhibited fewer initiatives and responses
      toward offspring than did mothers of premature singletons. Maternal behavior was
      predictive of cognitive development.

PMID- 11463145
TI  - Genetic and environmental influences on a measure of infant attachment security.
AB  - A twin study of infant attachment security at age 24 months was conducted on
      archival data for a sample of 99 MZ pairs and 108 DZ pairs from the Louisville
      Twin Study. MZ concordance for attachment was 62.6%, which was significantly
      greater than the DZ concordance of 44.4%. Concordances were transformed into
      polychoric correlations, and LISREL was used to conduct a quantitative genetic
      analysis of the data. Results indicated that 25% of the variability in attachment
      was attributable to genetic factors, and the remaining 75% was attributable to
      non-shared environmental effects. No evidence was found for a contribution from
      shared environmental influences to attachment security. Possible concerns about
      the validity of twin methodology are addressed and various interpretations of the
      results are presented.

PMID- 11463146
TI  - Parents' and teachers' ratings of problem behaviours in children: genetic and
      contrast effects.
AB  - We obtained ratings on the Conners' scales from teachers (CTRS-28) and parents
      (CPRS-48) for 61 monozygotic and 64 dizygotic twin pairs, aged between 7 and 11
      years. Model-fitting analyses were carried out to estimate the extent of genetic
      and environmental influences on problem behaviours, and to explore possible
      contrast effects in ratings by parents and teachers. Confirming previous findings
      with other measures, there was evidence of moderate to strong genetic effects on
      a range of problem behaviours. Parents' ratings on the Anxiety, Impulsive
      Hyperactive and Learning Problem sub-scales showed significant evidence of
      contrast effects. There was no evidence of such rater bias or competitive sibling
      interaction effects in ratings by teachers, or in parents' ratings on the Conduct
      Problem and Psychosomatic sub-scales.

PMID- 11463147
TI  - An exploration of the genetic and environmental etiology of heart rate in infancy
      and middle childhood.
AB  - Heart rate was recorded on 210 MZ and 174 DZ same sex twin pairs participating in
      the MacArthur Longitudinal Twin Study (MALTS) at age 14, 20, 24, 36 months and 7
      years. Heart rate was monitored in the laboratory at all ages. At ages 14 to 36
      months, heart rate was monitored prior to a set of cognitive tasks. At age 7
      years heart rate was recorded during a mood-eliciting videotaped presentation. At
      this age only heart rate monitored during neutral portions of the presentation
      were used. Mean heart rate declines substantially across this age range, but is
      similar in boys and girls and for MZ and DZ twins at each age. Heart rate is
      moderately correlated across all time points suggesting that individual
      differences in heart rate are relatively stable over this age range. Multivariate
      genetic and environmental models were fitted to the raw data. In general, genetic
      factors contribute to the stability of individual differences over time. Shared
      and non-shared environment factors tended to be occasion specific, with non
      shared environment contributing substantially to the individual variation at each
      age. Shared environment and non-shared environment also contributed a modicum to
      the stability across time. Thus, individual differences in resting heart rate is
      a relatively stable, heritable trait from infancy to early childhood.

PMID- 11463148
TI  - Genetics of testosterone and the aggression-hostility-anger (AHA) syndrome: a
      study of middle-aged male twins.
AB  - The aim of this study was to determine the genetic contribution to the variation
      in testosterone and the aggression-hostility-anger (AHA) syndrome in middle-aged
      twins. Moreover, the relation between testosterone and this syndrome, and
      possible common genetic mechanisms were investigated. Towards this end, blood
      samples were collected at two time points; the AHA syndrome was measured using
      three questionnaires: the Buss-Durkee Hostility Inventory with seven subscales,
      the Jenkins Activity Survey and the Spielberger State-Trait Anger Scale. The
      results showed substantial heritabilities for testosterone (approximately 60%)
      and moderate to fair heritabilities for the nine measures of the AHA syndrome (23
      53%). The best fitting model for testosterone at two time points included a small
      age component and additive genetic and unique environmental factors, while a
      multivariate analysis of the nine AHA subscales resulted in an independent
      pathway model with two common additive genetic and two common unique
      environmental factors. No correlation between the common genetic factor
      influencing testosterone and the AHA subscales was found. We did, however, detect
      a negative correlation between the common environmental factor underlying
      testosterone and both common environmental factors influencing the nine AHA
      subscales, which may reflect a tendency for testosterone levels to rise and
      hostility to drop (or vice versa) after repeatedly experiencing success (or
      failure).

PMID- 11463149
TI  - Categories of deltaF508 homozygous cystic fibrosis twin and sibling pairs with
      distinct phenotypic characteristics.
AB  - Cystic fibrosis (CF), the most common severe autosomal recessive trait among
      Caucasians, is caused by molecular lesions in the cystic fibrosis transmembrane
      conductance regulator gene (CFTR). The course of the multi-organ disease CF is
      highly variable, suggesting the influence of environmental factors and/or
      modulating genes other than CFTR on the disease phenotype. To evaluate the cause
      of CF disease variability, the European CF Twin and Sibling Study collected data
      on two clinical parameters most sensitive for the course and prognosis of CF, ie
      weight predicted for height (wfh)% (representative for the nutritional status)
      and FEVPerc (representative for the pulmonary status) for a cohort of 277 sibling
      pairs, 12 pairs of dizygous twins and 29 pairs of monozygous twins. Of these 318
      CF twin and sib pairs, 114 were reported to be homozygous for the most frequent
      CF disease-causing lesion, deltaF508. Intra-pair discordance was assessed by the
      intra-pair differences with wfh% and FEVPerc and by DELTA, a composite parameter
      defined by linear combination of wfh% and FEVPerc in order to describe
      discordance with respect to the overall disease severity. Monozygous twins had a
      significantly lower DELTA than dizygous twins (P = 0.05) indicating that CF
      disease severity is modulated by an inherited component in addition to the CFTR
      gene itself. Extreme phenotypes are considered to be more informative for the
      analysis of any quantitative trait. Thus, we aimed to quantify disease severity
      and intra-pair discordance in order to select pairs with the extreme phenotypes
      DIS (discordant patient pairs), CON+ (concordant and mildy affected patient
      pairs) and CON- (concordant and severely affected patient pairs). The algorithm
      reliably discriminated between pairs DIS, CON+ and CON- among the cohort of
      deltaF508 homozygotes. The selected pairs from these categories demonstrated non
      overlapping properties for wfh%, FEVPerc and the intra-pair difference of both
      parameters.

PMID- 11463150
TI  - Estimation of penetrance from twin data.
AB  - A simple method for estimating the gene frequency p and the penetrance value K
      from data on polymorphic monogenic characteristics on monozygotic twin pairs is
      presented. In spite of the method here presented having limited value because the
      results it yields cannot be evaluated on their own, the estimates of p and K it
      provides can be indirectly tested by comparing them to the ones obtained in
      familial aggregates through classical segregation analysis or by using the latter
      to calculate the expected proportions of dominant-dominant, dominant-recessive
      and recessive-recessive monozygotic twin pairs. When the method is applied to
      data on tongue-rolling ability published in the literature, a good agreement is
      observed between twin and familial estimates, thus indicating that the method is
      reliable and that it can be used as an ancillary way of corroborating or
      otherwise evidence of monogenic autosomal dominant mechanism inferred from the
      analysis of familial data.

PMID- 11463151
TI  - Anxiety and depression in twin and sib pairs extremely discordant and concordant
      for neuroticism: prodromus to a linkage study.
AB  - Multivariate modelling of anxiety and depression data in twins has suggested that
      the two phenotypes are largely underpinned by one genetic factor, while other
      studies have indicated a relationship between these disorders and the neuroticism
      personality trait. As part of a study to identify quantitative trait loci for
      anxiety and depression, questionnaire responses and interviews of 15,027
      Australian twins and 11,389 of their family members conducted during the past 20
      years were reviewed to identify individuals with neuroticism, anxiety and
      depression scores in the upper or lower deciles of the population. This
      information was then used to identify extreme discordant and concordant (EDAC)
      sib pairs. 1373 high-scoring and 1571 low-scoring subjects (2357 sib pairs) were
      selected for participation, and extremely high participation rates were achieved,
      with over 90% of contactable prospective participants completing the interview
      phase, and over 90% of these providing blood or buccal samples. Participation
      bias arising from the nature of the selection variables was minimal, with only a
      small difference between rates of interview participation among prospective
      participants with high and low selection scores (89.4% vs 91.6%). The interview
      permitted the diagnosis of depression and several anxiety disorders (OCD,
      agoraphobia, panic disorder, generalised anxiety disorder) in this sample
      according to DSM-IV criteria. The methodology for selection of prospective
      subjects was demonstrated to be extremely successful, with highly significant
      differences in depression and anxiety disorder prevalence rates between
      individuals in the two selection groups. The success of this EDAC sampling scheme
      will enhance the power for QTL linkage and association analysis in this sample.

PMID- 11463152
TI  - A population-based study of personality in 34,000 sib-pairs.
AB  - Several theoretical studies have suggested that large samples of randomly
      ascertained siblings can be efficiently used to ascertain phenotypically extreme
      individuals and increase power to detect genetic linkage. Phenotypes that can be
      reliably measured by questionnaire are of obvious utility for such selection
      strategies, as large numbers of individuals can be contacted without laborious
      individual interview. As the first step in developing a large randomly
      ascertained family cohort in southwest England, a sample of 88,000 individuals,
      including more than 34,000 sibling pairs in 20,000 sibships, was administered the
      Eysenck Personality Questionnaire (EPQ) by commercial mailing. The sample age
      ranges were 20-67 years and comprised 59% males and 41% females. Descriptive
      properties of the EPQ scales are similar to those reported from other large
      family cohorts. Test-retest correlations on 1681 probands in the sample are
      substantial for the N-scale (r = 0.93), but somewhat more modest for the other
      scales (range r = 0.70-0.88). Phenotypic and sibling correlations correspond
      quite closely to those of twin studies.

PMID- 11463153
TI  - GENESiS: creating a composite index of the vulnerability to anxiety and
      depression in a community-based sample of siblings.
AB  - There is considerable evidence for a unitary and dimensional view of the genetic
      vulnerability to symptoms of anxiety and depression. The GENESiS (Genetic
      Environmental-Nature of Emotional States in Siblings) Study aims to use a
      multivariate approach to detect genetic loci that contribute to individual
      differences in this vulnerability dimension. The study used the UK General
      Practice Research Framework to generate a community-based sample of siblings.
      Questionnaire measures of anxiety/depression included the short form of the
      neuroticism scale from the revised Eysenck Personality Questionnaire (EPQ-N), the
      General Health Questionnaire (GHQ-12), and the anxious arousal and high positive
      affect subscales from the Mood and Anxiety Symptoms Questionnaire (MASQ-AA and
      MASQ-HPA). Genetic model-fitting of 2658 unselected sibships provided evidence
      for a single common genetic (familial) factor that accounted for a substantial
      proportion of the genetic variances and covariances of these four measures. Using
      the parameter estimates of this model, we constructed a composite index of this
      common genetic factor. This index, which has a sib correlation of 0.22, will be
      used as a quantitative phenotype in the molecular genetic phase of GENESiS.

PMID- 11463154
TI  - Netherlands twin family study of anxious depression (NETSAD).
AB  - In a longitudinal study of Dutch adolescent and young adult twins, their parents
      and their siblings, questionnaire data were collected on depression, anxiety and
      correlated personality traits, such as neuroticism. Data were collected by mailed
      surveys in 1991, 1993, 1995 and 1997. A total of 13,717 individuals from 3344
      families were included in the study. To localise quantitative trait loci (QTLs)
      involved in anxiety and depression, the survey data were used to select the most
      informative families for a genome-wide search. For each individual a genetic
      factor score was computed, based on a genetic multivariate analysis of anxiety,
      depression, neuroticism and somatic anxiety. A family was selected if at least
      two siblings (or DZ twins) had extreme factor scores. Both discordant (high-low)
      and concordant (high-high and low-low) pairs were included in the selected
      sample. Once an extreme sibling pair was selected, all family members (parents
      and additional siblings of the selected pair) who had at least once returned a
      questionnaire booklet were asked to provide a DNA sample. In total, 2724
      individuals from 563 families (1007 parents and 1717 offspring) were approached
      and 1975 individuals from 479 families (643 patients and 1332 offspring) complied
      by returning a buccal swab for DNA isolation. All offspring from selected
      families were asked to participate in a psychiatric interview and in a 24-hour
      ambulatory assessment of cardiovascular parameters and cortisol. The interview
      consisted of the WHO-Composite International Diagnostic Interview and was
      administered to 1253 offspring. In this paper we describe the genetic
      epidemiological analyses of the survey data on anxiety, somatic anxiety,
      neuroticism and depression. We detail how these data were used to select families
      for the QTL study and discuss strategies that may help elucidate the molecular
      pathways leading from genes to anxious depression.

PMID- 11463155
TI  - Terminology for twin zygosity.

PMID- 11463156
TI  - The mechanism initiating and controlling monozygotic twinning in humans remains
      to be elucidated.

PMID- 11463157
TI  - Identical and fraternal: when words mislead.

PMID- 11463160
TI  - Luigi Gedda 1902-2000.

PMID- 11463161
TI  - Antioxidants in the treatment of Graves disease.
AB  - An antioxidant mixture (LAROTABE) was evaluated in the treatment of Graves
      disease. Fifty-six hyperthyroid patients were treated with methimazol (MMI) (A),
      LAROTABE (B), or MMI plus LAROTABE (C). According to a clinical score,
      improvement was obtained at 8 weeks in A and 4 weeks in B and C. Group A
      diminished their thyroid hormone concentration to normal levels, while patients
      with LAROTABE did not reduce T3 and T4 unless MMI was introduced. Hyperthyroid
      patients had increased malondialdehyde (MDA) content and SOD activity and
      decreased catalase activity compared to controls. Within group A, MDA decreased
      to control values while SOD was reduced 38.3% and catalase increased 21.6%.
      Similar results were obtained for MDA and for both enzymes after treatment with
      LAROTABE. Signs and symptoms of Graves disease might be related to an increase in
      free radicals; antioxidants could be a new therapeutic tool to improve the
      clinical manifestation of this illness.

PMID- 11463162
TI  - Disaccharide modulation of the mitochondrial membrane fluidity changes induced by
      the membrane potential.
AB  - The influence of the medium composition on the dynamic properties of
      mitochondrial membranes on depolarization was studied by following the
      fluorescence anisotropy changes of mitochondria-bound 1,6-diphenyl-1,3,5
      hexatriene (DPH) and hematoporphyrin (HP) as reporters, respectively, of lipid
      and protein regions. On collapse of the potential, the membrane fluidity
      increased in NaCl-, KCl-, and monosaccharide-based media and decreased in
      disaccharides. Infrared spectroscopy experiments suggested that disaccharides
      likely change water's structure and association on the membrane surface. These
      results indicate that disaccharides induce membrane perturbation, which may
      interfere in the study of structure-function correlation in biological membranes.

PMID- 11463163
TI  - Precursor of a novel scorpion venom peptide (BmKn1) with no disulfide bridge from
      Buthus martensii Karsch.
AB  - A full-length cDNA sequence encoding the precursor of a novel venom peptide
      (named BmKn1) with no disulfide bridge was first isolated from the venom gland
      cDNA library of Chinese scorpion Buthus martensii Karsch. The encoded precursor
      consisted of 70 amino acid residues including two parts: a signal peptide of 23
      residues, and a putative mature venom peptide (BmKn1) of 47 residues. The
      sequence of BmKn1 showed no similarity to those of other scorpion venom peptides.
      BmKn1 may be the first member of a new venom peptide family from scorpion. Future
      research will be interesting to unravel further the pharmacological function of
      this novel scorpion venom peptide.

PMID- 11463164
TI  - Intra- and intercellular distribution of mitochondrial probes and changes after
      treatment with MDR modulators.
AB  - Fluorescent probes are currently used to evaluate the mitochondrial transmembrane
      potential in situ. However, in parallel experiments using the probes JC-1 and
      TMRM in different cell types (human astrocytes, HEp-2, Vero, KB, and HeLa cells),
      we found that the distribution of JC-1 and TMRM is highly variable not only in
      different cell types but also in different cells of the same cell type, a
      condition that has never been documented until our work. This phenomenon depends
      on a hidden, widespread multidrug resistance (MDR) phenotype that can be
      recognized only by comparative assays with MDR inhibitors (progesterone,
      verapamil, and cyclosporin A) and represents a serious risk of error in the
      evaluation of the mitochondrial potential.

PMID- 11463165
TI  - Public funding of understanding nature.

PMID- 11463166
TI  - Casein kinase I: from obscurity to center stage.
AB  - The casein kinase I (CKI) family of protein kinases is a group of highly related,
      ubiquitously expressed serine/threonine kinases found in all eukaryotic organisms
      from protozoa to man. Recent advances in diverse fields, including developmental
      biology and chronobiology, have elucidated roles for CKI in regulating critical
      processes such as Wnt signaling, circadian rhythm, nuclear import, and
      Alzheimer's disease progression.

PMID- 11463167
TI  - Molecular basis of the anaerobic response in plants.
AB  - The response of plants to flooding is complex and involves the induction of
      specific gene sets. A multidisciplinary approach by several research teams has
      led to a reasonably good understanding of the low oxygen response, and many of
      the genes and proteins that are involved are known. But the factors that are
      critical in determining tolerance or intolerance remain unknown. Microarray
      technology offers renewed hope to unravel the complex changes in gene expression
      occurring in plants upon low oxygen treatment and what mechanisms are involved in
      the response.

PMID- 11463168
TI  - Are there large uncharted regions of tumor suppressor genes?

PMID- 11463169
TI  - Do rodents have a gene encoding glycogenin-2, the liver isoform of the self
      glucosylating initiator of glycogen synthesis?
AB  - The discovery of a second human gene, GYG2, encoding a liver-specific isoform of
      glycogenin, the self-glucosylating initiator of glycogen biosynthesis, raised the
      possibility for differential controls of this protein in liver and muscle. The
      new protein, glycogenin-2, had several properties similar biochemically to the
      muscle isoform, glycogenin-1, but unlike glycogenin-1, stable expression in
      fibroblasts led to a significant overaccumulation of glycogen. Ensuing attempts
      to generate reagents suitable for use with rodents, to examine the physiological
      regulation of glycogenin-2 by nutritional and hormonal factors, have been
      unsuccessful. Proof of a negative is difficult but the weight of the evidence is
      beginning to mitigate against the existence of a second glycogenin gene in
      rodents leading us to hypothesize that the presence of the GYG2 gene is limited
      to primates.

PMID- 11463170
TI  - Optical study of cytochrome cM formation in Synechocystis.
AB  - The expression of the cytM gene, which encodes cytochrome cM in Synechocystis sp.
      PCC 6803, is induced under stress conditions such as low temperature. Results of
      spectrophotometric studies revealed that cytochrome cM was oxidized by light
      absorbed by photosystem I in cells that had acclimatized to a low temperature.
      However, no similar light-induced oxidation of cytochrome cM was observed in
      delta cytM mutant cells. The kinetics of the oxidation and reduction of P700
      before and after acclimation of Synechocystis cells to low temperature suggested
      that cytochrome cM might donate electrons to photooxidized P700. Our observations
      indicate that cytochrome cM is synthesized under low-temperature stress and that
      it might carry electrons directly to P700+ in photosystem I.

PMID- 11463171
TI  - Transient up-regulation of liver mitochondrial thymidine kinase activity in
      proliferating mitochondria.
AB  - Administration of the fatty acid analogue tetradecylthioacetic acid (TTA) to
      rodents up-regulates peroxisomal and mitochondrial lipid-metabolizing enzymes and
      induces a proliferation of these organelles in hepatocytes. We show here that
      male NMRI mice fed a diet containing 0.3% (w/w) TTA revealed a transient two-fold
      increase in the incorporation of [3H]thymidine into the liver mtDNA followed by a
      1.6-fold increase in the content of mtDNA. In addition, a transient three-fold
      increase in the mitochondrial thymidine kinase (TK2) activity and a slight
      increase in the DNA polymerase gamma activity was observed, indicating that the
      TTA induced mitochondrial proliferation is linked to an up-regulation of the
      mitochondrial thymidine kinase activity.

PMID- 11463172
TI  - Adolescence and after.

PMID- 11463173
TI  - Neuromotor development from 5 to 18 years. Part 1: timed performance.
AB  - Timed performance in specific motor tasks is an essential component of a
      neurological examination applied to children with motor dysfunctions. This
      article provides centile curves describing normal developmental course and
      interindividual variation of timed performances of non-disabled children from 5
      to 18 years. In a cross-sectional study (n=662) the following motor tasks were
      investigated: repetitive finger movements, hand and foot movements, alternating
      hand and foot movements, sequential finger movements, pegboard, and dynamic and
      static balance. Intraobserver, interobserver, and test-retest reliability for
      timed measurements were moderate to high. Timed performances improved throughout
      the entire prepubertal period, but differed among various motor tasks with
      respect to increase in speed and when the 'adolescent plateau' was reached.
      Centile curves of timed performance displayed large interindividual variation for
      all motor tasks. At no age were clinically relevant sex differences noted, nor
      did socioeconomic status significantly correlate with timed performance. Our
      results demonstrate that timed motor performances between 5 and 18 years are
      characterized by a long-lasting developmental change and a large interindividual
      variation. Therefore, a well standardized test instrument, and age-specific
      standards for motor performances are necessary preconditions for a reliable
      assessment of motor competence in school-age children.

PMID- 11463174
TI  - Neuromotor development from 5 to 18 years. Part 2: associated movements.
AB  - Associated movements (AMs) are the most frequently assessed parameters of
      movement quality in children with motor dysfunctions. In this article, reference
      curves of duration and degree of AMs from 5 to 18 years are provided. In a cross
      sectional study of non-disabled children (n=662) duration and degree of AMs were
      estimated at six specific ages while children performed repetitive finger, hand,
      and foot movements, alternating hand and foot movements, diadochokinesis,
      sequential finger movements, pegboard, stress gaits, and dynamic balance.
      Moderate-to-high intraobserver and interobserver reliability for the assessment
      of AMs were noted. Duration and degree of AMs displayed a non-linear
      developmental course that was a function of the motor task's complexity. AMs
      decreased most with age in repetitive movements, less in alternating and
      sequential movements, and least in the pegboard and dynamic balance. Reference
      curves demonstrated large interindividual variations for duration and degree of
      AMs. Both the variable developmental course and large interindividual variation
      need to be taken into account in the assessment of movement quality of school-age
      children. In contrast to timed performance, considerable sex differences for AMs
      were observed.

PMID- 11463175
TI  - Abnormal developmental patterns of suck and swallow rhythms during feeding in
      preterm infants with bronchopulmonary dysplasia.
AB  - Infants with bronchopulmonary dysplasia (BFD) often have difficulty achieving
      coordinated suckle feeding. To analyze rhythmic differences during feeding in
      infants with BPD we performed weekly studies of 14 infants with BPD (eight male,
      six female; postmenstrual age [PMA] 32.1 to 39.7 weeks); and a PMA-matched
      control group without BPD (n=20), from initiation of bottle feeding until
      discharge, with simultaneous digital recordings of pharyngeal and nipple (teat)
      pressure. Unlike the control group, there was no significant correlation between
      PMA and stability of suckle rhythm, aggregation of suckles or swallows into runs,
      or length of suckle runs. Comparing those infants >35 weeks' PMA, the group with
      BPD had significantly decreased stability of suckle rhythm (increased coefficient
      of variation of suckle-suckle intervals: 0.34, SE 0.02 vs 0.254, SE 0.014;
      p=0.003), decreased aggregation into suckle runs (71.1, SE 3.4% vs 85.4, SE
      2%;p=0.001), and decreased length of suckle runs (7.2, SE 0.9 vs 13.1, SE 1.9
      suckles/run; p=0.003). Percentage of swallows in runs was also decreased in the
      cohort with BPD (58, SE 3.8% vs 77.2, SE 3.5%; p<0.001), as was length of swallow
      run (5.3, SE 0.5 vs 10.7, SE 1.1;p<0.001). Thus, in infants with BPD, anticipated
      maturational patterns of suckle and swallow rhythms did not occur. Delay in
      attainment of stable suckle and swallow rhythms in preterm infants, especially
      after 35 weeks' PMA, may predict subsequent feeding and neurological problems.

PMID- 11463176
TI  - Quality of life in preschool children born preterm.
AB  - The relationship of preterm birth to health-related quality of life (HRQoL) was
      examined for children aged 1 to 4 years. Three gestational age groups with a NICU
      history were selected, <32 weeks (n=65), 32 to 36 weeks (n=41), 237 weeks (n=54),
      and a reference group from the open population (n=50). The main instrument was
      the TNO-AZL Preschool Quality Of Life (TAPQOL) questionnaire, which was completed
      by the parents. In addition, other outcome measures obtained from parents or
      neonatologists were investigated. Children born <32 weeks had significantly lower
      HRQoL than the reference group in the scales for lungs, stomach, eating
      disorders, motor functioning, communication, and anxiety. Parental feelings
      towards the child were related to the child's HRQoL. We found differences between
      the neonatologists' and parents' perceptions of the children's situation, which
      can have clinical consequences (e.g. different opinions about what needed
      treatment). Neonatal intensive care after birth has HRQoL implications for all
      children, particularly in children born at <32 weeks of gestation.

PMID- 11463177
TI  - Are families with adolescents and young adults with cerebral palsy the same as
      other families?
AB  - This study compared adolescents with cerebral palsy (CP) and their families to
      adolescents without physical disabilities and their families as the child enters
      and leaves adolescence (age ranges 13 to 15 years and 19 to 23 years). Families
      of 90 individuals with CP (42 females, 48 males) and 75 individuals without
      physical disabilities (34 females, 41 males) participated. They completed the
      Family Assessment Device, Life Situation Survey, Multidimensional Scale of
      Perceived Social Support, and Future Questionnaire. There were few differences in
      family functioning, life satisfaction, or perceived social support between the
      groups. Expectations of young adults with CP and parents of both adolescents and
      young adults regarding future independence and success were lower than the
      expectations of the control group. While the group results emphasize similarities
      between families during the two stages of adolescence, individual families and
      individual family members report specific challenges.

PMID- 11463178
TI  - Characteristics and course of urinary tract dysfunction after acute transverse
      myelitis in.
AB  - Bladder involvement is common in transverse myelitis but its characteristics and
      natural history, particularly in relation to neurological outcome, have not been
      described in a paediatric population previously. Ten children, with ages ranging
      from 8 months to 16 years, who had a diagnosis of acute transverse myelitis were
      studied with video urodynamics and followed up in a tertiary paediatric
      neurourology clinic. Nine of ten children had obstructive urinary tract symptoms
      at presentation and all went on to develop 'irritative' urinary tract symptoms
      (frequency and urgency) about 1 month after initial presentation. Video
      urodynamics showed a combination of irritative (detrusor hyperreflexia) and
      obstructive (detrusor-sphincter dyssynergia) abnormalities in most patients and
      enabled management to be specifically directed towards these. The patients
      progress was followed up for a median duration of 36 months. All had residual
      bladder dysfunction, only four were asymptomatic on treatment. The degree of
      recovery of bladder function was not related to the degree of motor recovery.

PMID- 11463179
TI  - Angelman syndrome: evolution of the phenotype in adolescents and adults.
AB  - Individuals with Angelman syndrome (AS) have severe learning disability,* ataxia,
      seizures, dysmorphic facies, a happy, sociable disposition, and inability to
      speak. Most of the literature concerning the clinical features of AS has
      concentrated on younger children. This study aimed to look at the natural history
      of AS by documenting the clinical features in a group of 28 adolescents and
      adults with AS (12 males, 16 females; age range 16 to 40 years). Specific aspects
      studied included physical characteristics, general health, mobility, seizure
      disorder, behaviour and communication, and self-help skills. Problems seen in
      this older group of individuals differed significantly from those typically
      observed in younger children. The incidence of scoliosis and joint contractures
      increased with age. Facial features were more striking in adults. Hyperactivity
      and concentration improved and the sociable disposition persisted. There were
      subtle clinical differences between the groups of individuals with different
      underlying genetic abnormalities. Information obtained from this study is
      relevant to diagnosis and management of older individuals with AS.

PMID- 11463180
TI  - Quantitative evaluation of thalami and basal ganglia in infants with
      periventricular leukomalacia.
AB  - Quantitative analyses of cross-sectional areas of the thalami, caudate nuclei,
      and lentiform nuclei were performed in 29 preterm infants (16 males, 13 females;
      mean age 29.6 weeks, age range 27 to 24 weeks,) with periventricular leukomalacia
      (PVL). MRI was carried out in the infants between 9 and 18 months of corrected
      age and in 16 control infants. Bilateral thalami, caudate nuclei, lentiform
      nuclei, cerebral hemispheres, and cerebellum were measured by computer. Ratios of
      the areas of the thalami (Th), caudate nuclei (Ca), lentiform nuclei (Le), and
      cerebral hemispheres (CH) to that of the cerebellum (Ce) were calculated in each
      infant. The ratio of Th:Ce was significantly smaller in infants with moderate and
      severe PVL than in the control group bilaterally. Abnormal intensity areas were
      not observed in the thalami in any infants with PVL. CH:Ce was also smaller in
      infants with severe PVL than in the control group. No significant difference was
      observed between the groups in ratios Le:Ce or Ca:Ce. Results of our study
      suggest that the volume of the thalami is reduced and that thalamic involvement
      is present in infants with white matter lesions who have moderate to severe PVL.

PMID- 11463181
TI  - Functional MRI of visual cortex in sedated 18 month-old infants with or without
      periventricular leukomalacia.
AB  - Functional MRI (fMRI) of the visual cortex was evaluated in 42 sedated 18-month
      old infants (mean corrected age; 31 males, 11 females) with or without
      periventricular leukomalacia (PVL). Data from 14 infants could not be evaluated
      because of movement artefacts. Ten of the remaining 28 infants showed no
      significant fMRI response upon visual stimulation. In 18 infants, a significant
      signal change upon stimulation was found in the visual cortex: in 17 a signal
      decrease and in one a signal increase. Functional changes were located mainly in
      the anterior part of the visual cortex. Seven of the 28 infants had normal MRI
      and 21 showed variable occipital PVL. An fMRI response was equally frequent in
      infants without PVL (4 of 7 infants) and with PVL (14 of 21 infants). In
      conclusion, fMRI was shown to be feasible in sedated infants. No correlation was
      found between functional activation and the presence or absence of occipital PVL.
      Type of fMRI response (signal decrease) and localization (anterior part of the
      visual cortex) are different from those seen in adults, probably reflecting a
      combination of sedation effects and immaturity of the visual system. At present,
      fMRI is a highly promising research tool; its clinical relevance still has to be
      established.

PMID- 11463182
TI  - Tethering of the vertebral artery in the congenital arcuate foramen of the atlas
      vertebra: a possible cause of vertebral artery dissection in children.
AB  - Twelve children with vertebrobasilar artery stroke are reported (seven males,
      five females; aged 6 months to 15 years). Patient 1 showed an arcuate foramen in
      the posterior arch of the atlas, an anatomical variant occurring in 3 to 15% of
      the population. It was hypothesized that the presence of the arcuate foramen
      might cause tethering of the vertebral artery and lead to its dissection by
      repetitive trauma. Lateral plain films of the cervical spine in cases of
      posterior circulation stroke were taken. Eight of 11 patients showed aberrant
      arcuate foramina. Of the remaining three patients, one had normal cervical spine
      X-rays, one had an absent right posterior arch of the atlas following previous
      surgery for a cervical meningocele, and one patient had incomplete ossification
      of the vertebrae. Seven of the nine patients with arcuate foramina had vertebral
      angiograms. In all cases this showed the vertebral artery passing through the
      arcuate foramen before entering the brain and an appearance consistent with
      arterial dissection and occlusion at the same site below the foramen. Most
      documented cases of posterior circulation stroke in children follow trauma, which
      may be minimal or repetitive, with thrombotic occlusion of the artery at C1-C2
      level. The association with an arcuate foramen and its possible causative role in
      the genesis of posterior circulation stroke in children has not been previously
      recognized. There may be a causal association between the presence of an arcuate
      foramen, tethering of the vertebral artery in the foramen, and dissection from
      repetitive trauma with movement of the neck.

PMID- 11463183
TI  - Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance
      intelligence quotients.

PMID- 11463184
TI  - 'Cerebral herniation in pyogenic meningitis'.

PMID- 11463185
TI  - Adapting to heart conditions: a test of the hedonic treadmill.
AB  - This paper tests the hypothesis of hedonic adaptation by analyzing the role that
      a history of heart problems has on the ability to deal with future heart
      conditions. The results show that those who have had a heart condition in the
      past are less likely to report worse self-assessed health and emotional health
      due to the onset of a new condition than those who have not previously had
      exposure to heart trouble. The results are fairly supportive of the notion of a
      hedonic treadmill.

PMID- 11463186
TI  - Balancing incentives in the compensation contracts of nonprofit hospital CEOs.
AB  - Given the considerable insight into corporate governance achieved through studies
      of executive compensation in proprietary firms it is surprising that executive
      contracting in nonprofit organizations remains largely unexplored. In this paper,
      we use the multitask principal agent model of Holmstrom and Milgrom [The Journal
      of Law, Economics and Organization 7 (1991) (Suppl.) 24] to argue that nonprofit
      hospitals represent an optimal response to information asymmetries between
      managers and boards. For a board with multidimensional objectives, the agency
      problem is getting top executives to distribute their efforts across all
      dimensions of the hospital's mission. The nonprofit form is preferred because the
      absence of high powered incentives such as share ownership reduces executives'
      incentives to place undue emphasis on improving financial performance at the
      expense of important but less observable tasks. Using newly available
      compensation data we test the model by comparing the conditional distributions of
      earnings for industrial and nonprofit hospital CEOs in Ontario. Our best
      estimates are that CEOs in publicly traded firms earn twice as much on average as
      those in similarly sized nonprofit hospitals but bear roughly eight times the
      income variance. Estimates of the associated degree of risk aversion are well
      within conventional bounds and are consistent with the trade-off between
      insurance and incentives predicted by the theory.

PMID- 11463187
TI  - Long-term care and nursing home coverage: are adult children substitutes for
      insurance policies?
AB  - Recent theoretical work suggests that in some cases, parents will forego the
      purchase of long-term care insurance and rely on child-provided care in old age.
      This paper uses data from the Asset and Health Dynamics survey and the Panel
      Study of Income Dynamics to examine whether the availability of children and
      other potential caregivers explains why so few elderly persons have long-term
      care insurance. In contrast to the notion that family members serve as
      substitutes for long-term care insurance, variables measuring the availability of
      informal caregivers have no statistically significant effect in models of
      insurance ownership and models of intentions to purchase insurance.

PMID- 11463188
TI  - Medicaid reimbursement and the quality of nursing home care.
AB  - An influential series of papers have found that an increase in Medicaid
      reimbursement decreases the level of nursing home quality in the presence of
      certificate-of-need (CON) and construction moratorium regulations. Using more
      recent national data, an outcome-oriented measure of quality, and an alternative
      methodology, this study finds a positive, albeit small, effect of reimbursement
      on quality. Although this paper does find some evidence of excess demand within
      the market for nursing home care, this new finding is attributed to a decline in
      nursing home utilization over the last two decades.

PMID- 11463189
TI  - Do Medicaid physician fees for prenatal services affect birth outcomes?
AB  - This study exploits a natural experiment to examine the relationship between
      Medicaid physician fees and birth outcomes among a national sample of pregnant
      women. Applying a cohort difference-in-differences methodology, I find a
      significant negative association between these fees and the risk of low birth
      weight. I estimate that a 10% higher than average relative Medicaid fee is
      independently associated with a 0.074% lower absolute risk of low birth weight
      (<2.5 kg) and a 0.035% lower risk of very low birth weight (<1.5kg) among
      Medicaid-insured women. For low-income women, this association grows
      significantly. Lastly, I find a moderate association between these fees and use
      of first trimester prenatal services.

PMID- 11463190
TI  - Medical malpractice liability and its effect on prenatal care utilization and
      infant health.
AB  - In this paper we conduct the first national evaluation of the effect of
      malpractice liability pressure, as measured by malpractice premiums, on prenatal
      care utilization and infant health. Our results indicate that a decrease in
      malpractice premiums that would result from a feasible policy reform would lead
      to a decrease in the incidence of late prenatal care by between 3.0 and 5.9% for
      black women and between 2.2 and 4.7% for white women. Although, we found evidence
      that malpractice liability pressure was associated with greater prenatal care
      delay and fewer prenatal care visits, we did not find evidence that such pressure
      negatively affected infant health.

PMID- 11463191
TI  - The meaning of death: some simulations of a model of healthy and unhealthy
      consumption.
AB  - Simulations of a model of healthy and unhealthy consumption are used to
      investigate the impact of various terminal conditions on life-span, pathways of
      health-related consumption and health. A model in which life-span and the 'death'
      stock of health are fixed is compared to versions in which (i) the 'death' stock
      of health is freely chosen; (ii) life-span is freely chosen; (iii) both the
      'death' stock of health and life-span are freely chosen. The choice of terminal
      conditions has a striking impact on optimal plans. Results are discussed with
      reference to the existing demand for health literature and illustrate the
      application of iterative processes to determine optimal life-span, the role
      played by the marginal value of health capital in determining optimal plans, and
      the importance of checking the second-order conditions for the optimal choice of
      life-span.

PMID- 11463192
TI  - Dollars and performance: treating alcohol misuse in Maine.
AB  - If public funds are allocated efficiently, then an increase in funding should
      improve the performance of substance abuse treatment programs. In the data used
      in this paper, performance (measured as abstinence rates) and expenditures per
      patient are not positively correlated. One explanation is that funding is
      endogeneous, i.e. programs treating more difficult patients receive more funding.
      The data comes from all Maine's outpatient drug-free programs that received
      public funding between 1991 and 1994. After controlling for endogeneity, this
      paper concludes that the marginal impact of expenditures per patient on
      abstinence rates is small and statistically insignificantly different from zero.

PMID- 11463193
TI  - A comment on Neudeck and Podczeck's "adverse selection and regulation in health
      insurance markets".
AB  - Using the Grossman equilibrium concept, Neudeck and Podczeck [Journal of Health
      Economics 15 (1996) 387] show that imposing a minimum standard on a perfectly
      competitive insurance market can result in anti-competitive effects: decreased
      welfare with some insurers earning positive profits. However, the Grossman
      concept precludes an insurer from offering two separating, cross-subsidizing
      health plans. When an insurer can offer multiple plans (as under both the Nash
      and Miyazaki-Wilson equilibrium concepts), I show that minimum standards result
      in a doubleton equilibrium, never allow positive total profits, and increase
      welfare. This is of interest since in 1997 more than half of establishments in
      the US offering choice of multiple plans did so through a single insurer.

PMID- 11463194
TI  - Beam characteristics for various sizes of annular aperture on scanning electron
      microscope.
AB  - Using an analogy between light optics and electron optics, we have calculated
      beam characteristics such as the beam profile and the optical transfer function
      for several sizes of annular and circular apertures on a scanning electron
      microscope (SEM). It has been found that an annular aperture improves the image
      quality with regard to several kinds of image resolution and the depth of focus
      at the price of good low-frequency (nu) contrast. In contrast with conventional
      circular-aperture SEM images, a combination of a low-nu-pass filtered, circular
      aperture SEM image with a high-nu-pass filtered, annular-aperture SEM image has
      the potential to enhance the image quality in terms of both the image resolution
      and the depth of focus.

PMID- 11463195
TI  - The concept of high angle wedge polishing and thickness monitoring in TEM sample
      preparation.
AB  - The concept of high angle wedge polishing for TEM non-metal sample preparation is
      introduced for the first time. Also, introduced is the concept of converting
      lateral distance measurement into vertical thickness measurement in monitoring
      TEM sample thickness. Based on the Tripod polisher, Quadripod was constructed
      using these two concepts. Fast and reliable TEM sample preparation (mechanical
      polishing down to electron transparency) can be achieved using the Quadripod. In
      addition, Quadripod offers the ability of locating a specific area of interest.

PMID- 11463196
TI  - Image-spectroscopy--I. The advantages of increased spectral information for
      compositional EFTEM analysis.
AB  - The acquisition of a series of energy-filtered TEM images over the energy-loss
      range of interest creates a three-dimensional data set comprising both spatial
      and spectral information. Such an image-series contains energy-loss information
      not available with conventional two- or three-window methods, allowing standard
      techniques for quantitative EELS analysis to be applied to extracted 'image
      spectra'. The increase in spectral information enables improved ionisation edge
      background extrapolation and interactive image-spectrum analysis to be performed.
      In this paper, the many advantages of the image-spectroscopy approach are
      outlined by reference to an example of elemental segregation in an AlZnMgCu
      alloy.

PMID- 11463197
TI  - Image-spectroscopy--II. The removal of plural scattering from extended energy
      filtered series by Fourier deconvolution.
AB  - The increased spectral information obtained by acquiring an EFTEM image-series
      over several hundred eV allows plural scattering to be removed from loss images
      using standard deconvolution techniques developed for the quantification of EEL
      spectra. In this work, both Fourier-log and Fourier-ratio deconvolution
      techniques have been applied successfully to such image-series. Application of
      the Fourier-log technique over an energy-loss range of several hundred eV has
      been achieved by implementation of a novel method that extends the effective
      dynamic range of EFTEM image-series acquisition by over four orders of magnitude.
      Experimental results show that the removal of plural scattering from EFTEM image
      series gives a significant improvement in quantification for thicker specimen
      regions. Further, the recovery of the single-scattering distribution using the
      Fourier-log technique over an extended energy-loss range is shown to result in an
      increase in both the ionisation-edge jump-ratio and the signal-to-noise ratio.

PMID- 11463198
TI  - Structure determination at the atomic level from dynamical electron diffraction
      data under systematic row conditions.
AB  - We discuss a method to obtain structural information on crystals at the atomic
      level in high-resolution transmission electron microscopy from dynamical
      diffraction data under systematic row conditions. Working at a fixed incident
      energy and within an N-beam approximation, data is required at a well defined set
      of N incident beam orientations to determine the scattering matrix, one
      orientation for each column in the matrix. At each orientation the corresponding
      column of the scattering-matrix is obtained by Fourier transformation of the exit
      surface wave function. Thus, in addition to each exit surface image, we must
      recover the phase of the wave function for that orientation in the image plane.
      We show that retrieval of the phase using algorithms based on conservation of
      flux, which assume continuity of the phase, can yield incorrect solutions for the
      phase. This is because singularities can occur in the phase of the wave field at
      points where the intensity is zero, which can lead to edge dislocations in the
      phase. We demonstrate, using a model example, how these edge dislocations arise.
      We will show that phase retrieval from a through focal series of measurements or
      using the Gerchberg-Saxton algorithm (starting from measurements of an image and
      the corresponding diffraction pattern), correctly retrieves the phase and hence
      the exit surface wave function for all the orientations required to obtain the
      scattering-matrix. The dynamical (multiple) scattering can then be inverted to
      uniquely obtain the projected potential.

PMID- 11463199
TI  - Contamination and the quantitative exploitation of EELS low-loss experiments.
AB  - Quantitative exploitation of the low-loss domain of electron energy loss spectra
      is based on an accurate determination of the corresponding signal intensity
      profile. This signal can be erroneous and contains artefacts as a result of
      sample contamination in the microscope, for example. The consequences of
      contamination on the signal intensity of the low-loss spectra are discussed. In
      the case of a carbonaceous contamination, a simple additional spurious signal can
      be considered, as has been demonstrated in the case of a Si single crystal, a
      highly oriented pyrolytic graphite (HOPG) and a strontium titanate single crystal
      (SrTiO3). The linear variation of the rate of contamination with time allows the
      implementation of a simple method based on the subtraction of the spurious signal
      in order to correct for the contamination effect. The relative errors induced by
      the carbonaceous contamination on the determination of the optical properties of
      SrTiO3 are estimated.

PMID- 11463200
TI  - The Turkish commercial health insurance industry.
AB  - Turkey has experienced significant development in the private health insurance
      market since 1991. Improvements in private health services, increased public
      awareness, and insufficient service delivery by the social security organizations
      have encouraged more people to buy private health insurance. The number of people
      covered by private health insurance has reached 600,000, forming a $200 million
      market. The Turkish insurance industry is targeting 6-8 million insurance holders
      before the year 2005. This study examines the structure of the commercial health
      insurance industry of Turkey and gives the latest policy and legal changes made
      in the insurance market by the Turkish government to affect supply and demand.

PMID- 11463201
TI  - Management strategies and financial performance in rural and urban hospitals.
AB  - This study identifies the difference in financial performance between rural and
      urban hospitals and examines whether or not that difference may be attributed to
      the emphasis of revenue enhancement over cost management strategies. Hospitals in
      Virginia were included in this study except for the two state university medical
      centers. Rural and urban hospitals were compared on 10 performance indicators
      grouped into four categories: revenues, costs, profits, and productivity. The
      results suggest that rural hospital profitability is dependent on cost
      management. Since rural hospitals achieved lower cost, better efficiency and
      productivity level than urban hospitals in Virginia, they demonstrate a
      significant higher level of profit.

PMID- 11463202
TI  - Possible electromagnetic interference with electronic medical equipment by radio
      waves coming from outside the hospital.
AB  - Electromagnetic interference (EMI) with electronic medical equipment by radio
      waves from mobile telephone handsets has been reported and is currently receiving
      wide attention. The possibility of EMI with electronic medical equipment by radio
      waves coming into the hospital has also been pointed out. But so far, there are
      no reports measuring the frequency distribution of electric field intensity
      induced by incoming radio waves. Therefore, we measured electric field intensity
      induced by radio waves coming into our 11-floor hospital, which was under
      construction. The maximum intensity observed was about 200 V/m at 2.79 GHz, from
      airport surveillance radar waves. The maximum intensity induced by radio waves
      from cellular phone base stations was 1.78 V/m. These data show that various
      frequencies of radio waves are common in this urban area, and that they induce
      strong electricfield intensity. This strong electric field intensity might cause
      EMI with electronic medical equipment. Measurement of the electromagnetic
      environment should be done by each hospital in urban areas to prevent EMI with
      electronic medical equipment.

PMID- 11463203
TI  - Categorization of fetal heart rate patterns using neural networks.
AB  - Digitized data from CTG (cardiotocography) measurements (fetal heart rate and
      uterine contractions) have been used for categorization of typical heart rate
      patterns before and during delivery. Short time series of CTG data, about 7 min
      duration, have been used in the categorization process. In the first part of the
      study, selected CTG data corresponding to 10 typical cases were used for purely
      auto associative unsupervised training of a Self-Organizing Map Neural Network
      (SOM). The network may then be used for objective categorization of CTG patterns
      through the map coordinates produced by the network. The SOM coordinates were
      then compared. In the second part of the study, a hybrid neural network
      consisting of a SOM network and a Back-Propagation network (BP) was trained with
      data corresponding to a number of basic heart rate patterns as described by eight
      manually selected indices. Test data (different than the training data) were then
      used to check the performance of the network. The present study shows that the
      categorization process, in which neural networks were used, can be reliable and
      agree well with the manual categorization. Since the categorization by neural
      networks is very fast and does not involve human efforts, it may be useful in
      patient monitoring.

PMID- 11463204
TI  - Molecular physiology of neuronal K-ATP channels (review).
AB  - ATP sensitive potassium (K-ATP) channels are widely expressed in many cell types
      including neurons. K-ATP channels are heteromeric membrane proteins that consist
      of two very different subunits: the pore-forming, two-transmembrane spanning
      potassium channel subunit (Kir6) and the regulatory, 17 transmembrane spanning
      sulphonylurea receptor (SUR). This ensemble--joined together in a 4:4
      stoichiometry--endows this channel with a unique combination of functional
      properties. The open probability of K-ATP channels directly depends on the
      intracellular ATP/ADP levels allowing the channels to directly couple the
      metabolic state of a cell to its electrical activity. Here, recent progress on
      the molecular composition and functional diversity of neuronal K-ATP channels is
      reviewed. One is particular concerned with single-cell mRNA expression studies
      that give insight to the coexpression patterns of Kir6 and SUR isoforms in
      identified neurons. In addition, the physiological roles of neuronal K-ATP
      channels in glucose sensing and adapting neuronal activity to metabolic demands
      are discussed, as well as their emerging pathophysiological functions in acute
      brain ischemia and chronic neurodegenerative diseases.

PMID- 11463205
TI  - Cationic lipid-mediated transfection in vitro and in vivo (review).
AB  - Recent rapid developments in genomics will likely lead to a rapid expansion in
      identifying defective genes causing a variety of diseases, implying a vast
      increase in the number of therapeutic targets. Treatment of such diseases may
      include strategies ranging from gene delivery and replacement to antisense
      approaches. For successful development of gene therapies, a minimal requirement
      involves the engineering of appropriate gene- or oligonucleotide-carrier systems,
      which are necessary for protective purposes (against nucleases) and transport (to
      target tissue and cells in vivo). Further, they should also display the
      propensity to efficiently translocate the oligonucleotides and gene constructs
      into cells, via passage across several membrane barriers. The emphasis in this
      review will be on the use of cationic lipids for that purpose. Crucial to
      successful application of this sophisticated technology in vivo will be a need
      for a better understanding of fundamental and structural parameters that govern
      transfection efficiency, including the issues of cationic lipid/DNA complex
      assembly (with or without helper lipid), stability towards biological fluids,
      complex-target membrane interaction and translocation, and gene-integration into
      the nucleus. Biophysical and biochemical characterization of so-called
      lipoplexes, and their interaction with cells in vitro, are considered
      instrumental in reaching such insight. Here, most recent advances in cationic
      lipid-mediated gene delivery are discussed from such a perspective.

PMID- 11463206
TI  - The multi-structural feature of the multidrug resistance gene product P
      glycoprotein: implications for its mechanism of action (hypothesis).
AB  - P-glycoprotein is a member of the ATP-binding cassette (ABC) transport
      superfamily. It plays an important role in the development of multidrug
      resistance in cancers by effluxing a wide variety of anticancer drugs. A large
      amount of information on the structure and function of P-glycoprotein has been
      accumulated over recent years from studies using molecular, biochemical, and
      biophysical approaches. It remains unclear, however, how this protein folds in
      membranes and how it transports such a wide variety of hydrophobic compounds.
      This paper highlights the recent progress in the structural and biogenesis
      aspects of P-glycoprotein. A model mechanism of P-glycoprotein action is proposed
      as a hypothesis that is based on recent progress in studying the topological
      folding of P-glycoprotein.

PMID- 11463207
TI  - Early stage shape change of human erythrocytes after application of electric
      field pulses.
AB  - Erythrocytes which receive electric field pulses are subject to poration, fusion
      and shape changes due to electrodynamic forces, aminophospholipid perturbation
      and influences on the normal flip-flop process. The shape change characteristics
      of cells suspended in different media were analysed after application of
      rectangular electric field pulses from t=11-44 micros and from E=4-8 kV/cm.
      Albumin is shown to decelerate the echinocyte shape change within the first few
      seconds after pulse application. The addition of fluoride and vanadate
      accelerates the shape change due to their inhibiting influence on the
      aminophospholipid translocase. For both the duration of the field pulse and its
      field strength, there exist lower threshold values under which no early stage
      shape change is observable. The activation energy calculated from the dissipative
      influence of the electric field alone is smaller than expected, indicating the
      electrodynamic influence on the flip-flop process. Cell shapes were additionally
      analysed by contour tracing to focus on the echinocyte spicule distribution after
      pulse application. This image analysis revealed that, with an increase of both
      pulse duration and field strength, the shape change velocity and the shape change
      intensity increase.

PMID- 11463208
TI  - Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat
      equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside
      transporter proteins produced in Xenopus oocytes.
AB  - In the present study, one has determined the relative role of plasma membrane
      equilibrative (Na+-independent) ENT nucleoside transport proteins (particularly
      ENT2) in the uptake of antiviral nucleoside analogues for comparison with the
      previously reported drug transport properties of concentrative (Na+-dependent)
      CNT nucleoside transport proteins. The human and rat nucleoside transport
      proteins hENT1, rENT1, hENT2 and rENT2 were produced in Xenopus oocytes and
      investigated for their ability to transport three 3'-deoxy-nucleoside analogues,
      ddC (2'3'-dideoxycytidine), AZT (3'-azido-3'-deoxythymidine) and ddI (2'3'
      dideoxyinosine), used in human immunodeficiency virus (HIV) therapy. The results
      show, for the first time, that the ENT2 transporter isoform represents a
      mechanism for cellular uptake of these clinically important nucleoside drugs.
      Recombinant h/rENT2 transported ddC, ddI and AZT, whilst h/rENT1 transported only
      ddC and ddI. Relative to uridine, h/rENT2 mediated substantially larger fluxes of
      ddC and ddI than h/rENT1. Transplanting the amino-terminal half of rENT2 into
      rENT1 rendered rENT1 transport-positive for AZT and enhanced the uptake of both
      ddC and ddI, identifying this region as a major site of 3'-deoxy-nucleoside drug
      interaction.

PMID- 11463209
TI  - Erythrocyte agglutination by wheat germ agglutinin: ionic strength dependence of
      the contact seam topology.
AB  - The topology of the cell-cell contact seam formed when normal or pronase pre
      treated (PPT) erythrocytes are exposed to wheat germ agglutinin (WGA) in isotonic
      media of different ionic strengths was examined here. Lectin uptake and cell
      agglutination were also quantified. Agglutination of normal cells was gradually
      and significantly inhibited as ionic strength (IS) was reduced from 0.15
      (buffered 145 mm NaCl) to 0.105. Agglutination was less inhibited in PPT cells,
      even when IS was reduced to 0.09. Cell contact seams formed during agglutination
      showed patterns of localized contacts. The scale of the patterns, i.e. the
      average lateral separation distance of contact regions, was 0.62 microm for
      normal cells and was significantly shorter, at 0.44 microm, for PPT cells at an
      IS of 0.15. The scale increased significantly for both cell types when the IS was
      reduced to 0.09. Flow cytometry measurements showed that WGA uptake by normal
      cells increased slightly, whilst that for PPT cells was unchanged, as IS was
      decreased from 0.15 to 0.09. The results imply that, whilst ionic strength change
      does not exert a strong influence on intermolecular WGA-ligand binding, physico
      chemical modification of the interaction between cells modulates not only the
      extent and progression of the biospecific lectin-induced cell-cell agglutination
      but also the topology of the contact seam. The IS dependence of contact
      separation in WGA-agglutinated cells is contrasted here with that reported for
      cells adhering in dextran solutions. The influence of IS change and pronase pre
      treatment on contact pattern are consistent with predictions, from interfacial
      instability theory, of punctuate thinning of the aqueous layer separating bilayer
      membranes in close apposition.

PMID- 11463211
TI  - Circadian programming in cyanobacteria.
AB  - Prokaryotic cyanobacteria express robust circadian (daily) rhythms under the
      control of a timing mechanism that is independent of the cell division cycle.
      This biological clock orchestrates global regulation of gene expression.
      Competition experiments demonstrate that fitness is enhanced when the circadian
      period is consonant with the period of the environmental cycle. Mutational
      analyses have identified three clock genes in the organism, one of which is
      related to DNA recombinases and helicases. We propose a new model for the core
      'clockwork' that implicates rhythmic changes in the status of the chromosome that
      underly the rhythms of gene expression.

PMID- 11463212
TI  - A fungus among us: the Neurospora crassa circadian system.
AB  - Neurospora crassa is the only molecular genetic model system for circadian
      rhythms research in the fungi. Its strengths as a model organism lie in its
      relative simplicity--compared to photosynthesizing and vertebrate organisms, it
      is a stripped-down version of life. It forms syncitial hyphae, propagates and
      reproduces, and the circadian clock is manifest in numerous processes therein. As
      with other model circadian systems, Neurospora features a
      transcription/translation feedback loop that is fundamental to an intact
      circadian system. The molecular components of this loop converge with those of
      blue light photoreception, thus bringing the clock and one of its input pathways
      together.

PMID- 11463213
TI  - The Drosophila circadian clock: what we know and what we don't know.
AB  - Circadian rhythms are regulated by endogenous body clocks, which are formed by
      rhythmic cycles of clock gene expression. Almost all reviews of the Drosophila
      circadian clock state that the intracellular oscillator is based on a simple
      negative feedback loop. However, not many 'simple' feedback loops in biology last
      for 24 h. Instead, the Drosophila clock is a series of precisely timed steps that
      are deliberately slow. In this paper, I will discuss the current model for how
      the Drosophila clock is regulated, and ask what questions remain to be answered.

PMID- 11463214
TI  - The mammalian circadian clock shop.
AB  - In mammals, a master circadian pacemaker driving daily rhythms in behavior and
      physiology resides in the suprachiasmatic nucleus (SCN). The SCN contains
      multiple circadian oscillators that synchronize to environmental cycles and to
      each other in vivo. Rhythm production, an intracellular event, depends on more
      than eight identified genes. The period of the rhythms within the SCN also
      depends upon intercellular communication. Many other tissues also retain the
      ability to generate near 24 -h periodicities although their place in the
      organization of circadian timing is still unclear. This paper focuses on the
      tissue-, cellular- and molecular-level events that generate and entrain circadian
      rhythms in behavior in mammals and emphasizes the apparent differences between
      the SCN and peripheral oscillators.

PMID- 11463215
TI  - The molecular genetics of circadian rhythms in Arabidopsis.
AB  - While a number of physiological and biochemical processes in plants have been
      found to be regulated in a circadian manner, the mechanism underlying the
      circadian oscillator remains to be elucidated. Advances in the identification and
      characterization of components of the plant circadian system have been made
      largely through the use of genetics in Arabidopsis thaliana. Results so far
      indicate that the generation of rhythmicity by the Arabidopsis clock relies on
      molecular mechanisms that are similar to those described for other organisms, but
      that a totally different set of molecular components has been recruited to
      perform these functions.

PMID- 11463216
TI  - Photic entrainment of the circadian clock: from Drosophila to mammals.
AB  - Entrainment is as fundamental to an organism's circadian timing as are the
      molecular mechanisms involved in the functioning of the intracellular clock
      oscillator. In nature, one of the principle, although not the only, circadian
      entraining stimulus (Zeitgeber) is provided by the daily light--dark cycles. In
      animals, the visual processing apparatus alone is inadequate to accomplish the
      task of transducing circadian photic signals to the clockwork machinery. In fact,
      it is ever more appreciated by circadian biologists that organisms as divergent
      as plants and mammals have evolved a wonderfully complex array of partly
      redundant specializations which can guarantee the precise alignment of biological
      and environmental time. Research in circadian biology is cruising at such a rate
      that attempts to review the state of the art can only hope, at best, to provide a
      snapshot of the speeding cruiser from its wake. This paper will hopefully provide
      a reasonably sharp portrayal of what is at hand.

PMID- 11463217
TI  - How does the circadian clock send timing information to the brain?
AB  - This paper discusses circadian output in terms of the signaling mechanisms used
      by circadian pacemaker neurons. In mammals, the suprachiasmatic nucleus houses a
      clock controlling several rhythmic events. This nucleus contains one or more
      pacemaker circuits, and exhibits diversity in transmitter content and in axonal
      projections. In Drosophila, a comparable circadian clock is located among period 
      expressing neurons, a sub-set of which (called LN-vs) express the neuropeptide
      PDF. Genetic experiments indicate LN-vs are the primary pacemakers neurons
      controlling daily locomotion and that PDF is the principal circadian transmitter.
      Further definition of pacemaker properties in several model systems will provide
      a useful basis with which to describe circadian output mechanisms.

PMID- 11463220
TI  - Australia's campaign to eradicate bovine tuberculosis: the battle for freedom and
      beyond.
AB  - In 1970, voluntary State-based TB control programs in Australia were replaced by
      a coordinated national campaign to eliminate both brucellosis and tuberculosis
      from the cattle population. The campaign was funded and managed under tripartite
      agreement by State/Territory and Commonwealth governments and Industry. The
      tuberculosis component of the campaign relied on test and slaughter with
      surveillance for the disease in abattoirs and trace-back to property of origin an
      essential component. Because of the moderate sensitivity of the skin test (
      approximately 70%), testing was repeated at prescribed intervals over a number of
      years. In the more hostile environment of northern Australia, novel strategies
      were developed to maximize musters and remove 'at risk' animals. Australia is
      fortunate it did not have a feral host for M. bovis (apart from buffalo, which
      were included in the campaign) to complicate eradication. A national granuloma
      submission program was implemented in 1992 to increase the intensity of abattoir
      monitoring. Selective or total depopulation was used in some herds to achieve the
      requirements of the national Standard Definitions and Rules of the Campaign and
      achieve the status of 'TB Free Area' in December 1997. Monitoring for
      tuberculosis has continued under the 5-year Tuberculosis Freedom Assurance
      Program and measures to further reduce the risk of new cases have been
      implemented.

PMID- 11463221
TI  - Tuberculosis in cattle: new perspectives.
AB  - Today, the risk to human health is at a low level in most developed countries.
      This has shifted the emphasis to the trading implications of the disease in
      cattle and has led to a deterioration in the appreciation of risk by all except
      those who are directly affected by the occurrence of tuberculosis in their herd.
      The success of earlier national bovine tuberculosis eradication programmes was
      achieved at a time when herds were smaller, the intensity and demands of
      production lower, and before the emergence of a significant wildlife reservoir of
      Mycobacterium bovis. There are other impediments to eradication, however, not
      least of which are the limitations of the tuberculin test and the failure
      adequately to address other environmental sources of M. bovis. Provided the
      security of the herd is established, then the use of the tuberculin test can
      generally be relied upon to detect infection in exposed herds. The strategic use
      of cytokine assays can provide a further means of identifying infected cattle and
      ensuring their early removal. However, if infection has been introduced into the
      herd by means other than an infected bovine animal, then the security offered by
      the programme of tuberculin testing, in the absence of other control measures, is
      of limited value.Geographical information and data management systems can now be
      used to identify those areas where tuberculosis is currently being actively
      disseminated and where additional resources can most usefully be deployed. A
      clearer understanding of the mode of herd to herd transmission of M. bovis can
      thus be achieved and this can lead to a broader approach to the control and
      eradication of this zoonotic disease.

PMID- 11463222
TI  - Cattle-to-cattle transmission of Mycobacterium bovis.
AB  - This review, illustrated with data on the characteristics of herds infected with
      Mycobacterium bovis (TB) in Great Britain (GB), attempts to identify the role of
      cattle-to-cattle transmission (CCT) of TB. CCT plays a part in the entry of
      infection into herds, through purchased infected animals or contiguous spread,
      although CCT can have a relatively small role in comparison with an established
      wildlife source. Experimental studies have shown that it is possible for CCT to
      occur within herds. In 1999, more than one reactor was found in over two-thirds
      of confirmed TB incidents in Great Britain. The details of transmission from an
      infectious animal to a susceptible animal are described: proximate, which depends
      on factors such as closeness of contact and ventilation, or indirect, which also
      depends on survival outside the host. Herd size is a risk factor for the
      incidence of TB, both in herds and in individual cattle. Control of TB is
      considered in relation to the skin test: failure of the test to remove all
      infected animals from incidents is possible, but probably of less significance
      than failure to prevent reinfection from sources external to the herd. It is
      concluded that CCT may have significance in determining the total number of
      reactors. Safeguarding herds from other sources of TB is likely to reduce CCT as
      a side effect.

PMID- 11463223
TI  - Wildlife disease reservoirs: the epidemiology of Mycobacterium bovis infection in
      the European badger (Meles meles) and other British mammals.
AB  - Mycobacterium bovis infection has been confirmed in a wide range of mammals hosts
      throughout the world. The European badger (Meles meles) and the brushtail possum
      (Trichosurus vulpecula) are implicated as significant sources of infection for
      domestic cattle in the UK and New Zealand respectively. The risk of transmission
      of infection between a wildlife population and domestic animals will be
      determined by both the epidemiology of the disease and the ecology of the host.
      In the UK, surveys by the UK Ministry of Agriculture, Fisheries and Food (MAFF)
      have identified M. bovis infection in deer (Cervus sp., Capreolus sp., Dama sp.),
      red fox (Vulpes vulpes), mink (Mustela vison), feral ferret (Mustela furo), mole
      (Talpa europaea), brown rat (Rattus norvegicus) and feral cat (Felis catus).
      However, the potential contribution to cattle herd breakdowns, of reservoirs of
      M. bovis infection in mammals other than the badger is poorly understood and is
      the subject of current research. In contrast, M. bovis infection in the badger
      has been the subject of a long term ecological and epidemiological study at
      Woodchester Park in South-West England, where the prevalence and distribution of
      infection in a wild population has been intensively monitored. The pattern of
      infection in the population and potential risks to cattle, are profoundly
      influenced by badger social organization and behaviour. The pattern of land use
      and cattle farming practices in the UK brings badgers into close contact with
      domestic animals and provides conditions that may enhance the likelihood of
      disease transfer.

PMID- 11463224
TI  - Models of Mycobacterium bovis in wildlife and cattle.
AB  - Following the first model of wildlife tuberculosis (in European badgers) there
      has been a spate of papers modelling wildlife TB. These have looked at population
      parameters and disease dynamics in the badger and possum. Recent papers in
      particular have looked at various methods of controlling the wildlife vector to
      reduce the incidence of TB in cattle. The author examines the role of modelling
      to show what insights it has given us, which issues have not been addressed, and
      where the shortfalls lie. Particular attention will be paid to a comparison
      between models of badgers and possums, and between simple and more complex
      models, and possible areas of future research will be revealed.

PMID- 11463225
TI  - Towards more accurate diagnosis of bovine tuberculosis using defined antigens.
AB  - Diagnostic accuracy is of paramount importance in test-and-slaughter programmes
      for the eradication of bovine tuberculosis (TB). Currently applied methods, such
      as in vivo skin testing and in vitro interferon-gamma (IFN- gamma) testing,
      utilize purified protein derivatives (PPDs), which are poorly-defined mixtures
      containing many individual antigenic components. It is known that false-positive
      responses to these reagents can occur in cattle which are not infected with TB,
      largely because of that antigenic complexity. This paper reviews recent
      approaches to the characterization of more precisely defined diagnostic tools
      which can be used to develop tests with greater specificity. For example, the low
      mass secreted protein ESAT-6 has been shown to be capable of differentiating TB
      infected cattle from those which develop responsiveness to PPD through contact
      with environmental mycobacteria or vaccination with BCG. The information which
      has accumulated in recent years has shown that the increased specificity is
      associated with some decrease in test sensitivity, but the overall advantages of
      being able to make precise diagnostic decisions will have significant advantages
      in many situations.

PMID- 11463226
TI  - Mycobacterium bovis infection in human beings.
AB  - The causative agent of bovine tuberculosis, Mycobacterium bovis, is also
      responsible for some cases of tuberculosis in human beings. Although recognized
      for over a century, this form of human tuberculosis has been a source of
      considerable misunderstanding and controversy. Questions still remain concerning
      the relative virulence of M. tuberculosis and M. bovis in human beings, the risk
      of human disease after infection, the immunological consequences of infection
      that does not proceed to disease, the occurrence of human-to-human transmission
      of M. bovis and the health risk of diseased human beings to cattle. The advent of
      the HIV/AIDS pandemic raises new questions of the epidemiological impact of
      immunosuppression on the transmission of M. bovis to and between human beings.
      Although largely eradicated in the developed nations, bovine tuberculosis still
      occurs in many developing nations and epidemiological data on the impact of this
      on human health is scanty but, in the light of the increasing incidence of
      tuberculosis worldwide, it is urgently needed.

PMID- 11463227
TI  - Pathogenesis of tuberculosis in cattle.
AB  - There has been a renewed interest in the pathogenesis of bovine tuberculosis in
      many countries, in an attempt to understand better its transmission, to improve
      diagnosis and assess the potential of vaccination. This paper, which overviews
      current knowledge of aspects of the pathogenesis of bovine tuberculosis, draws
      from studies of field cases and experimental infections and highlights
      deficiencies in current understanding. The pathogenesis of bovine tuberculosis
      has not received the same level of attention as with human tuberculosis, and in
      many instances, the processes involved in bovine tuberculosis have been drawn
      from studies of human tuberculosis or from small animal models of infection. This
      paper however, considers the successful emulation of naturally acquired
      tuberculosis using experimental cattle models and identifies the complex and
      integrated nature of microbiological, immunological and pathological events
      involved. Current understanding of the initiation of infection, immune responses,
      and subsequent pathology, which can vary significantly in individual animals are
      discussed. Whilst there are aspects of M. bovis that still remain elusive to
      scientific investigation, further studies on the pathogenesis of bovine
      tuberculosis are advocated as necessary to provide a better scientific basis on
      which to review control and eradication strategies, which are currently less than
      effective in many regions.

PMID- 11463228
TI  - Pathogenesis of pulmonary Mycobacterium bovis infection: basic principles
      established by the rabbit model.

PMID- 11463229
TI  - Virulence factors of Mycobacterium bovis.
AB  - Virulence factors of Mycobacterium bovis are the special properties that enable
      it to infect, survive, multiply and cause disease in an animal host. An
      understanding of these factors will lead to new strategies including an effective
      vaccine to control bovine tuberculosis. A few factors have already been
      identified and two broadly different approaches to discover other virulence
      factors are now being used. In the first approach, libraries of random M. bovis
      mutants are produced, the likely attenuated mutants are identified using a
      screening technique and the interrupted genes in selected mutants are identified.
      In the second approach, genes encoding putative virulence factors are selected by
      a range of different methods and then inactivated, usually by allelic exchange,
      to produce likely attenuated mutants of M. bovis. In both approaches, loss of
      virulence by a mutant must be determined in an animal model. Subsequently, the
      mutant must be complemented back to virulence with an active form of the
      identified gene in order to demonstrate that loss of virulence was not due to
      polar effects of the mutation on nearby genes. It is almost certain that most of
      the virulence factors of M. bovis are the same as those of the classical human
      tuberculosis organism, Mycobacterium tuberculosis, as both organisms can cause
      identical clinical disease in humans and are genetically very similar. Many
      putative virulence genes are now being investigated and only the inherent
      slowness with which mycobacterial work proceeds, delays the inevitable arrival of
      an exciting new phase in the understanding of mycobacterial disease.

PMID- 11463230
TI  - Immune responses in bovine tuberculosis.
AB  - Knowledge of the immune responses which develop in cattle following infection
      with Mycobacterium bovis is essential both to the understanding of disease
      pathogenesis and to the logical development of immune-dependent tools, such as
      diagnostic tests and vaccines, which can be used to combat the disease. Studies
      of field cases of bovine tuberculosis (TB) and of experimental bovine models of
      M. bovis infection have indicated that cell-mediated immune responses (CMI)
      predominate within a spectrum of immunity which exists. This paper reviews
      aspects of recent research and indicates how knowledge of T-cell antigenic
      targets in bovine TB along with increasing knowledge of T-cell subpopulations and
      their interactions with M. bovis -infected macrophages provides opportunities for
      the development of better methods for disease control.

PMID- 11463231
TI  - Immunology and vaccinology of tuberculosis: can lessons from the mouse be applied
      to the cow?
AB  - The nature of both innate and acquired immunity in the lungs are both still
      poorly understood, and how these two sets of mechanisms intersect with each other
      may have considerable bearing on the overall expression of host resistance. While
      the central role of CD4 T cells in the acquired phase is well established, cells
      bearing this marker may also contribute to innate immunity in the guise of both
      NK-positive and negative innate populations capable of secreting gamma
      interferon. In contrast, expansion of an antigen-specific memory T cell
      population is the purpose of current vaccine strategies, and several interesting
      and promising types of new candidates are briefly discussed.

PMID- 11463232
TI  - In vitro control of Mycobacterium bovis by macrophages.
AB  - Mycobacterium bovis is frequently seen inside macrophages in vivo. The outcome of
      M. bovis infection depends on T cell interactions with macrophages, however
      mycobacteria are thought to be relatively resistant to macrophage killing. Little
      is known about the immunological mechanisms which control intracellular growth of
      M. bovis, and in the absence of T cell help the organism is capable of
      intracellular survival and replication. We have investigated the role of
      macrophages in controlling growth of virulent M. bovis or M. bovis BCG in vitro.
      At a multiplicity of infection of 5:1, macrophages from a range of animal species
      including cattle, deer, possums, ferrets and mice restricted growth of BCG while
      M. bovis grew progressively. Inter-species variation in controlling growth of M.
      bovis by alveolar macrophages was observed. Pre-treatment of macrophages with
      interferon-gamma and lipopolysaccharide inhibited intracellular growth of M.
      bovis. Addition of freshly recruited macrophages further inhibited M. bovis, and
      intracellular growth was arrested by activated fresh macrophages. Our
      observations suggest that naive macrophages can prevent BCG growth, while T cell
      activation in conjunction with freshly recruited macrophages is required for
      preventing growth of M. bovis.

PMID- 11463233
TI  - Vaccination of cattle against Mycobacterium bovis.
AB  - Protection of cattle against bovine tuberculosis by vaccination could be an
      important control strategy in countries where there is persistence of
      Mycobacterium bovis infection in wildlife and in developing countries where it is
      not economical to implement a 'test and slaughter' control programme. Early field
      trials with Bacille Calmette Guerin (BCG) M. bovis vaccine in cattle produced
      disappointing results, with induction of tuberculin skin-test reactivity
      following vaccination and low levels of protection. However, recent studies using
      a low dose of BCG vaccine in cattle have produced more encouraging results and
      field trials should now be carried out in developing countries to determine
      whether this low dose BCG vaccination strategy will reduce the spread of
      infection. The options for new candidate tuberculosis vaccines have increased
      markedly in the last decade with the advent of new attenuated strains of M.
      bovis, and sub-unit protein and recombinant DNA vaccines. Some of these new types
      of vaccines have recently been tested in cattle. New attenuated M. bovis vaccines
      induced greater protection than BCG vaccine in cattle which had been sensitized
      to environmental mycobacteria prior to vaccination. In contrast, it has proved
      difficult to stimulate appropriate immune responses in cattle necessary for
      protection with sub-unit protein and recombinant DNA vaccines and better
      immunological adjuvants are required for these types of vaccines. Progress in the
      development of new tuberculosis vaccines has been very rapid in the past decade
      and the prospects for vaccination to control and eradicate bovine tuberculosis
      are encouraging.

PMID- 11463234
TI  - Optimal models to evaluate the protective efficacy of tuberculosis vaccines.
AB  - BCG has been used widely as a vaccine to prevent tuberculosis (TB) for 80 years,
      yet there is still considerable controversy about its efficacy. Many experimental
      variables have obscured the true efficacy of BCG. The absence of appropriate
      animal models for the study of protective efficacy and the lack of in vitro
      correlates of protective immunity have impeded progress. Laboratory animal
      studies, which have contributed to understanding the pathogenesis, heritability
      of resistance and immunology of TB, have failed to identify the immunological
      pathways necessary for protective immunity. In recent years, cattle and deer,
      which are naturally susceptible to TB, have been used to study protective
      immunity in vaccinated animals, challenged with virulent bacteria. A deer TB
      infection model has been developed that can measure protection against TB
      infection or the development of disease. Data from this model show that,
      providing live BCG is administered in a short interval prime-boost protocol,
      significant protection against infection and disease can be obtained. Single dose
      vaccine provides suboptimal protection that attenuates pathology but does not
      prevent infection. Low dose BCG vaccine (10(4)cfu), administered in a prime-boost
      protocol, sufficient to prevent infection, does not cause conversion to delayed
      type hypersensitivity or produce unacceptable side-effects. Immune memory for
      protection against infection persists at optimal levels for at least 12 months
      post vaccination. Used optimally, BCG produces good levels of protection against
      TB and improved protocols or its use should be explored, before attempts are made
      to replace it with new-generation vaccines. It is now possible to integrate the
      fundamental information obtained from laboratory animals with studies of
      functional immune protection in target host species. Justification for the use of
      TB vaccines for domestic livestock under field conditions, must be underpinned by
      scientific evidence that they provide acceptable levels of protection long term.

PMID- 11463235
TI  - A coordinated strategy for evaluating new vaccines for human and animal
      tuberculosis.
AB  - There is a remarkable convergence in the current efforts to develop and evaluate
      new tuberculosis (TB) vaccine candidates for use in humans, domestic animals, and
      wild animal reservoirs. It is quite likely that similar vaccination strategies
      will prove useful in these diverse host species. Many TB vaccine candidates are
      being screened for protective efficacy in conventional laboratory animals (e.g.
      mouse, guinea pig), in captive wild species under laboratory conditions (e.g.
      brushtail possum), and in the target hosts (e.g. cattle, deer). These systems
      share some important features, e.g. direct challenge infection of the lung by
      intratracheal or aerosol exposure, and the use of bacterial enumeration, and
      gross and microscopic histopathology, as the readouts. Some TB vaccine candidates
      have been tested in many models, yielding important insights into common
      mechanisms of resistance to Mycobacterium tuberculosis and M. bovis, and
      providing evidence of the vaccine's ability to induce protection under widely
      different circumstances. Coordination of this global search for better TB
      vaccines, irrespective of target species, would facilitate the rapid application
      of new technologies and maximize the sharing of materials and experiences between
      human and veterinary TB researchers. The creation of liaisons between TB vaccine
      research efforts of government-sponsored medical and agricultural research
      programs, international bodies such as the World Health Organization (WHO) and
      the European Community (EC), private foundations and the vaccine industry, will
      yield a high return.

PMID- 11463236
TI  - BOVIGAM: an in vitro cellular diagnostic test for bovine tuberculosis.
AB  - BOVIGAM which is based on the detection of gamma interferon (IFN- gamma) is a
      rapid, laboratory assay of a cell mediated immune response that may be used for
      the detection of tuberculosis (TB) infection in animals. Whole blood is first
      incubated overnight with bovine PPD, avian PPD or negative control antigens, and
      IFN- gamma in the supernatant plasma is then measured by EIA. TB infection is
      indicated by a predominant IFN- gamma response to bovine PPD. Since 1988, BOVIGAM
      has been extensively trialed on more than 200 000 cattle in Australia, Brazil,
      Ireland, Northern Ireland, Italy, New Zealand, Romania, Spain and the USA.
      Sensitivity has varied between 81.8% and 100% for culture-confirmed bovine TB and
      specificity between 94% and 100%. The IFN- gamma assay detects M. bovis infection
      earlier than the skin test and in New Zealand is applied to detect skin-test
      negative cattle with TB, where after slaughter a significant number of IFN- gamma
      reactors have TB. BOVIGAM is also approved in New Zealand for serial testing skin
      test positive cattle when non-specificity is suspected. Cattle are tested 7-30
      days after a positive caudal fold test. The boosting effect of the skin test on T
      cell activity allows blood to be cultured with PPD up to 30 h after collection
      without effecting accuracy. The BOVIGAM results are not affected by poor
      nutritional condition and are only mildly and briefly affected by dexamethasone
      treatment and parturition. IFN- gamma responses of cattle vaccinated with BCG are
      dose-dependent and short-lived. The BOVIGAM kit is now used routinely in many
      countries for the detection of M. bovis infected cattle, buffalo and goats.

PMID- 11463237
TI  - Genomics of Mycobacterium bovis.
AB  - The imminent completion of the genome sequence of Mycobacterium bovis will reveal
      the genetic blueprint for this most successful pathogen. Comparative analysis
      with the genome sequences of M. tuberculosis and M. bovis BCG promises to expose
      the genetic basis for the phenotypic differences between the tubercle bacilli,
      offering unparalleled insight into the virulence factors of the M. tuberculosis
      complex. Initial analysis of the sequence data has already revealed a novel
      deletion from M. bovis, as well as identifying variation in members of the PPE
      family of proteins. As the study of bacterial pathogenicity enters the
      postgenomic phase, the genome sequence of M. bovis promises to serve as a
      cornerstone of mycobacterial genetics.

PMID- 11463238
TI  - Comparative genomics of BCG vaccines.
AB  - Bacille Calmette-Guerin (BCG) vaccines have been given to more people than any
      other vaccine. They have also probably resulted in as much controversy as any
      other vaccine. In clinical trials, the efficacy of BCG vaccination against
      pulmonary TB has been widely variable. At the same time, a number of
      investigators have observed phenotypic differences between BCG daughter strains,
      raising the possibility that differences between BCG products may in some way
      translate into different outcomes. With recent genomic analysis of BCG strains,
      it has become possible to piece together the molecular events that have resulted
      in current BCG vaccines. Between the derivation of BCG in 1921 and the
      lyophilization of BCG Pasteur 1173 in 1961, there have been at least seven
      genetic events, including deletions, duplications and a single nucleotide
      polymorphism. The phenotypic relevance of these changes in BCG vaccines remains
      to be explored.

PMID- 11463239
TI  - Molecular epidemiology of Mycobacterium bovis: exploiting molecular data.
AB  - 'Molecular epidemiology' is defined as the integration of conventional
      epidemiological approaches with molecular techniques to track specific strains of
      pathogens in order to understand the distribution of disease in populations. It
      has become a very powerful tool in the study of Mycobacterium tuberculosis and
      human tuberculosis, where it has been exploited to provide 'added value' to
      conventional epidemiological approaches (contact tracing) and has often
      challenged accepted dogmas. It has been used to confirm epidemiologically
      suspected transmission, to detect epidemiologically unsuspected transmission, to
      identify risk factors and environments where transmission is occurring, to detect
      laboratory errors and to monitor the efficacy of tuberculosis control programmes.
      For Mycobacterium bovis and bovine tuberculosis, molecular epidemiology has a key
      role to play in providing more precise epidemiological data on the issues of
      interbovine transmission and the role of wildlife reservoirs in disease
      maintenance and transmission. M. bovis strains may also differ in key biological
      properties, such as virulence, transmissibility, stability and antigenic
      variation, which may help to explain field observations. There may be correlation
      between strain type and 'herd level' factors such as breakdown size etc.
      Molecular 'strain typing' studies have provided useful information in several
      countries, notably New Zealand, where strain typing data is used as an integral
      part of M. bovis control schemes, to influence the level of herd testing or
      wildlife control and to define the extent and spread of infected wildlife. This
      presentation will review the methods and approaches currently appropriate for M.
      bovis strain typing and will review selected applications as well as discussing
      future perspectives and challenges for the application of molecular epidemiology
      to bovine tuberculosis.

PMID- 11463240
TI  - Immunodiagnosis of bovine tuberculosis. Summary of a satellite workshop of the
      Mycobacterium bovis 2000 conference, Cambridge, UK, 17 August 2000.

PMID- 11463241
TI  - Report from the 1st Comparative Workshop on the Pathology of Mycobacterial
      Infections.

PMID- 11463242
TI  - Third International Conference on Mycobacterium bovis, St John's College,
      Cambridge, 13-17 August 2000. Workshop on Vaccine Development for Domestic
      Livestock and Wildlife.

PMID- 11463243
TI  - Cattle TB schemes; control or eradication; a critical reappraisal.

PMID- 11463244
TI  - A biomimetic approach to dihydrobenzofuran synthesis.
AB  - A method for an acid-catalyzed construction of dihydrobenzofuran heterocycles
      (14) from 2-(2'-hydroxyethyl)quinone precursors 10 is presented. The putative
      oxonium ion intermediate 17 formed by an intramolecular hydroxyl cyclization
      followed by dehydration is reduced in situ by an added dihydroquinone source.
      Good to excellent yields of cyclized products are realized in all cases except
      for highly electron deficient systems, and these suffer reduction prior to
      oxonium ion formation. All products are monomeric and derived from a two-electron
      transfer except for 10 g, which affords the dimeric dihydrobenzofuran. The amount
      of cyclization or reduction product is governed by the HOMO/LUMO gap between the
      quinone substrate and the dihydroquinone additive, and the product distribution
      can be adjusted by modifying the electronic properties of the added reducing
      agent.

PMID- 11463245
TI  - Supramolecular assemblies between macrocyclic porphyrin hexamers and star-shaped
      porphyrin arrays.
AB  - The syntheses of eight new star-shaped D(3)-symmetric arrays in which three 15
      (pyrid-4-yl)porphyrin subunits are attached to the 1, 3, and 5 positions of a
      benzene core through linkers consisting of collinear repetitive phenylethynyl
      units have been carried out using Pd(0)-catalyzed coupling reactions. By the same
      procedure, an analogous 10-(4-pyridin-yl)porphyrin hexamer in which all positions
      of the benzene core are substituted has been obtained. Likewise, the preparation
      of suitably sized cyclic porphyrin hexamers, in which all six or at least three
      alternate porphyrin rings are complexed with Zn(II) ions, is described in detail.
      In solution, such cyclic porphyrin hexamers form supramolecular assemblies with
      the star-shaped polyporphyrins in which the latter are held in the interior of
      the macrocycle through coordination of the apical pyridine rings with the Zn(II)
      ions. The suggested structures are supported by (1)H NMR spectroscopic and MALDI
      TOF mass spectrometric measurements. They agree with the high values of the
      binding constants of the corresponding supramolecules, which range between K =
      1.1 x 10(10) and 1.4 x10(9) M(-1).

PMID- 11463246
TI  - The effect of neighboring 1- and 2-adamantyl group substitution on the
      conformations and stereodynamics of N-methylpiperidine. Dynamic NMR spectroscopy
      and molecular mechanics calculations.
AB  - When a 1-adamantyl or a 2-adamantyl substituent is introduced at the 2-position
      in N-methylpiperidine, four different chair conformations are possible.
      Experimental observation using dynamic NMR spectroscopy and molecular mechanics
      calculations agree that the chair conformation with an equatorial adamantyl group
      and an axial methyl group is by far the most stable, but in both cases a minor
      population of a second conformation is demonstrated and characterized.
      Interaction between adamantyl and methyl groups is much more conformation
      determining than any preference for equatorial over axial location which
      predominates in simpler 2-substituted N-methylpiperidines.

PMID- 11463247
TI  - Nucleophilic substitution by a hydroxide ion at a vinylic carbon: ab initio and
      density functional theory studies on methoxyethene, 3-methoxypropenal, 2,3
      dihydro-4H-pyran-4-one, and 4H-pyran-4-one.
AB  - Nucleophilic substitutions by a hydroxide ion at vinylic carbons of methoxyethene
      (system A), 3-methoxypropenal (system B), 2,3-dihydro-4H-pyran-4-one (system C),
      and 4H-pyran-4-one (system D) were calculated by Becke's three-parameter hybrid
      density functional-HF method with the Lee-Yang-Parr correlation functional
      (B3LYP//B3LYP) and the second-order Moller-Plesset theory (MP2//B3LYP) using the
      6-31+G(d) and AUG-cc-pVTZ basis sets. In addition, bulk solvent effects (aqueous
      solution) were estimated by the polarized continuum (overlapping spheres) model
      (PCM-B3LYP//B3LYP) and the polarizable conductor PCM model (CosmoPCM
      B3LYP//B3LYP). The mechanisms as well as the influence of resonance, cyclic
      strain, aromatic, and polar effects on the reactivity of the calculated systems
      were determined. In the gas phase the rate-determining step of nucleophilic
      vinylic substitutions by a hydroxide ion may be either addition of hydroxide ion
      at the vinylic carbon (systems A and B) or elimination of the leaving group
      (systems C and D). In aqueous solution, for all four systems investigated,
      addition of hydroxide ion at the vinylic carbon is rate determining.

PMID- 11463248
TI  - Induction of diastereoselectivity in Fe(II) tris(amino acid-bipyridine)
      complexes.
AB  - A group of iron(II) tris-bipyridine complexes bearing L-amino acids (L-Lys, L
      Phe, L-Ser, L-Val) was prepared to investigate the predetermination of chirality
      of metal complexes by the chiral amino acid subunits. Noncovalent interactions
      and solvent polarity seemed to be important factors in inducing
      diastereoselectivity of the metal complexes. These phenomena were explained by
      (1)H NMR and CD spectroscopic studies and molecular mechanics calculations.

PMID- 11463249
TI  - Fluorescent charge-neutral analogue of xanthosine: synthesis of a 2'
      deoxyribonucleoside bearing a 5-aza-7-deazaxanthine base.
AB  - A concise route is described to prepare the 5-aza-7-deazapurine 2'-deoxyriboside
      (4), which presents the puADA hydrogen-bonding pattern, analogous to the hydrogen
      bonding pattern presented by 2'-deoxyxanthosine (2). The route begins with the
      commercially available 1-alpha-chloro-2-deoxy-3-5-bistoluoyloxyribofuranose (10),
      which proves to be a versatile point of entry to beta-2'-deoxyribofuranosides. In
      the first step, 2-nitroimidazole (8) is coupled with 10 to yield intermediate 11.
      Reduction of the nitro group to an amino group yields 12, which is treated with
      phenyl isocyanatoformate to complete the nucleobase to yield 13. Removal of the
      toluoyloxy protecting groups of 13 yields the target nucleoside 4 in 40% overall
      yield in four steps. In an alternative strategy, convergent coupling of 14 with
      10 under basic conditions was attempted but found to yield the heterocycle
      glycosylated at the undesired position. Compound 13 displays potentially useful
      fluorescence properties. After excitation at 250 nm, a solution of 13 in MeCN
      shows a fluorescence emission with a maximum at 410 nm. Furthermore, 13 is
      neutral at physiological pH, a property that it shares with natural nucleobases
      but not xanthosine itself, which is an acid with a pK(a) of ca. 5.6. Furthermore,
      as part of the design, 4 is made capable of presenting an unshared pair of
      electrons to the DNA minor groove.

PMID- 11463250
TI  - Nucleophilicity toward ketenes: rate constants for addition of amines to aryl
      ketenes in acetonitrile solution.
AB  - Second-order rate constants (k(Nu)) have been measured for the addition of amines
      to ketenes 4-6 in acetonitrile solution by the laser flash photolysis technique.
      These ketenes are formed from a photochemical Wolff rearrangement of diazoketones
      1-3, respectively. For all diazoketones studied, the presence of amines as
      nucleophiles in the reaction medium results in the formation of an intermediate
      that later converts to the amide. The rate of formation of these intermediates is
      linearly dependent on amine concentration. Various classes of amines, such as
      primary, secondary, and tertiary, aromatic, and aliphatic, have been used to
      investigate the ketene reactivity, and rate constants in the range 10(4)-10(9) M(
      1) s(-1) have been measured. Reaction rates are dependent upon steric effects in
      both the ketene and the nucleophile, which is consistent with a reaction
      mechanism involving nucleophilic attack at Calpha in the molecular plane of the
      ketene. On the basis of these data, a set of N(+) parameters for the reaction of
      amines with ketenes was determined.

PMID- 11463251
TI  - Oxidation of nitrobenzylic carbanions with dimethyldioxirane. new synthesis of
      quinomethanes and nitrobenzylic carbinols. First examples of methylation of
      carbanions with dimethyldioxirane.
AB  - The reaction of nitrobenzylic carbanions with dimethyldioxirane (DMD) results in
      oxidation at the carbanion center or at the nitronate center to give
      nitrobenzylic carbinols or quinomethanes, respectively. Minor amounts of the
      methylation products are also formed. Both of these processes were observed for
      carbanions of (p-nitroaryl)diarylmethanes. The outcome of the oxidation process
      is very sensitive to the reaction conditions.

PMID- 11463252
TI  - A study of electronic effects on the kinetics of thermal deamination of N
      nitrosoamides.
AB  - N-4-R-Benzyl-N-nitrosopivalamides (1a-d; R = MeO, Me, H, NO(2)) were allowed to
      decompose at 18 degrees C in C(6)D(12), CDCl(3), CD(3)CN, and d(6)-DMSO, and the
      rates of decomposition were followed by (1)H NMR spectroscopy. The half-lives of
      the nitrosoamides were found to vary in a systematic way with the nature of the R
      group on the aromatic nucleus. Electron-releasing groups were found to decrease
      the stability of the starting nitrosoamide, whereas electron-withdrawing ones
      increased the nitrosoamides' thermal stability. A Hammett-type plot of log(rate
      constants of deamination) vs sigma(p) was linear (R(2) = 0.986) with a rho-type
      value of -0.90 indicating development of significant positive charge at the
      benzylic position in the transition state of the rate-determining step. The
      thermal stability of the nitrosoamides was also found to be systematically
      affected by the polarity of the solvent: as the solvent polarity increased, so
      did the lability of the nitrosoamides. This observation of intra- and
      intermolecular electronic perturbations of the kinetics of nitrosoamide
      decomposition appears to be novel. A closer look at the rate-determining step of
      nitrosoamide thermolysis is made, and a mechanistic framework is proposed that
      accounts for both steric and electronic modulation of nitrosoamide stability as
      well as the greater thermal stabilities of the related N-nitrocarboxamides and N
      nitrosotosylamides.

PMID- 11463253
TI  - C(60)-based triads with improved electron-acceptor properties:
      pyrazolylpyrazolino[60]fullerenes.
AB  - A series of triad pyrazolylpyrazolino[60]fullerenes has been prepared in one pot
      from suitably functionalized hydrazones by 1,3-dipolar cycloaddition reactions
      under microwave irradiation. The electrochemical properties of the compounds
      obtained were investigated by cyclic voltammmetry, and they show better electron
      acceptor character than the parent C(60) in all cases. Fluorescence experiments
      and time-resolved transition spectroscopy indicate the existence of photoinduced
      charge-transfer processes with the C(60) triplet acting as the acceptor.

PMID- 11463254
TI  - Atropisomerism of the C-1-C'-1 axis of 2,2',8,8'-unsubstituted 1,1'-binaphthyl
      derivatives.
AB  - The Suzuki coupling of optically active (S)-binaphthyl bromide 10 with (S)
      binaphthyl boronic acid 11 produced a diastereomeric mixture of
      tetrahydroxyquaternaphthyls 4. The coupling products 4as well as their
      derivatives 5-7 can be considered as members of the family of 1,1'-binaphthyl
      3,3'-diols. The C-1-C'-1 axis of all these compounds was found to have an
      unusually high rotational barrier. Generally, the barrier is higher for
      derivatives having more bulky substituents at the 3 and 3' positions.

PMID- 11463255
TI  - An unusual decarboxylative Maillard reaction between L-DOPA and D-glucose under
      biomimetic conditions: factors governing competition with Pictet-Spengler
      condensation.
AB  - In 0.1 M phosphate buffer at pH 7.4 and 37 degrees C, the tyrosine metabolite L
      3,4-dihydroxyphenylalanine (L-DOPA) reacts smoothly with D-glucose to afford,
      besides diastereoisomeric tetrahydroisoquinolines 1 and 2 by Pictet-Spengler
      condensation, a main product shown to be the unexpected decarboxylated Amadori
      compound N-(1-deoxy-D-fructos-1-yl)-dopamine (3). Under similar conditions,
      dopamine gave only tetrahydroisoquinoline products 4 and 5, whereas L-tyrosine
      gave exclusively the typical Amadori compound 6. Fe(3+) and Cu(2+) ions, which
      accumulate in relatively high levels in parkinsonian substantia nigra, both
      inhibited the formation of 3. Cu(2+) ions also inhibited the formation of 1 and 2
      to a similar degree, whereas Fe(3+) ions increased the yields of 1 and 2.
      Apparently, the formation of 3 would not be compatible with a simple
      decarboxylation of the initial Schiff base adduct, but would rather involve the
      decarboxylative decomposition of a putative oxazolidine-5-one intermediate
      assisted by the catechol ring. These results report the first decarboxylative
      Maillard reaction between an amino acid and a carbohydrate under biomimetic
      conditions and highlight the critical role of transition metal ions in the
      competition with Pictet-Spengler condensation.

PMID- 11463256
TI  - Two-carbon homologation of aldehydes via silyl ketene acetals. 2. Study of the
      stereochemical control in the formation of (E)-alkenoic acids.
AB  - The condensation of C,O,O-tris(trimethylsilyl)ketene acetal 1 with aldehydes 2 in
      the presence of catalytic amounts of mercuric iodide at room temperature affords
      syn and anti beta-trimethylsiloxy alpha-trimethylsilyl alkanoic acid silyl esters
      3 in good yields. These new compounds gave, under acidic or basic conditions, E
      and (or) Z enoic acids 4. The paths for the formation of these alkenoic acids are
      discussed.

PMID- 11463257
TI  - Semisynthesis of D-ring modified taxoids: novel thia derivatives of docetaxel.
AB  - Two novel 5(20)-thia analogues of docetaxel have been synthesized from 10
      deacetylbaccatin III or taxine B and isotaxine B. The key step of these syntheses
      is the concomitant thietane ring formation and acetylation of the tertiary
      alcohol at C-4. Both compounds are less cytotoxic than docetaxel but have
      divergent activity on microtubule disassembly.

PMID- 11463258
TI  - Synthesis of 5-epi-[6-(2)H(2)]valiolone and stereospecifically monodeuterated 5
      epi-valiolones: exploring the steric course of 5-epi-valiolone dehydratase in
      validamycin A biosynthesis.
AB  - In validamycin A biosynthesis, as well as that of acarbose, the valienamine and
      validamine moieties are ultimately derived from a C(7) sugar, sedoheptulose 7
      phosphate, which is cyclized to 2-epi-5-epi-valiolone by a cyclase that operates
      via a dehydroquinate (DHQ) synthase-like mechanism. 2-epi-5-epi-Valiolone is
      first epimerized at C-2 to give 5-epi-valiolone and then dehydrated between C-5
      and C-6 to yield valienone. To probe the dehydration mechanism of 5-epi-valiolone
      to valienone, stereospecifically 6alpha- and 6beta-monodeuterated 5-epi
      valiolones were synthesized. The key step in the synthesis was desulfurization of
      the tetrabenzyl-6,6-bis(methylthio)-5-epi-valiolone and introduction of the
      deuterium utilizing Zn, NiCl(2), ND(4)Cl/D(2)O, and THF. Extensive studies using
      various combinations of protio- and deuteroreagents and solvents probed the
      mechanism of the reductive desulfurization, which is crucial for the preparation
      of stereospecifically monodeuterated 5-epi-valiolones. Incorporation experiments
      with the labeled precursors in the validamycin A producer strain, Streptomyces
      hygroscopicus var. limoneus, revealed that the dehydration of 5-epi-valiolone to
      valienone occurs by a syn elimination of water.

PMID- 11463259
TI  - Tuning lipase enantioselectivity in organic media using solid-state buffers.
AB  - The enantioselectivity exhibited by Candida antarctica lipase B (CALB) in
      predominantly organic media has been studied for different enzyme protonation
      states. Alcoholysis of (+/-)-2-phenyl-4-benzyloxazol-5(4H)-one (1) using butan-1
      ol as the nucleophile in low-water organic solvents was used as a model reaction.
      Using either organo-soluble bases or the newly introduced solid-state buffers of
      known pK(a), the protonation state of the lipase was altered. By choice of the
      appropriate solid-state buffer or organic base, the enantioselectivity could be
      selectively tuned. Both Et(3)N and the solid-state buffer pair CAPSO/CAPSO.Na
      were found to increase the enantioselectivity of the reaction catalyzed by CALB
      and that of another lipase (Mucor miehei). Significant differences to both the
      enantioselectivity and catalytic rate were observed, especially under hydrated
      conditions where byproduct acid was formed.

PMID- 11463260
TI  - Development of a new carbon-carbon bond forming reaction. new organic chemistry
      of sulfur dioxide. Asymmetric four-component synthesis of polyfunctional
      sulfones.
AB  - At low temperature 1-alkoxy-1,3-dienes add to sulfur dioxide activated by a Lewis
      or Bronstedt acid and generate zwitterionic intermediates that can be quenched by
      enoxysilanes. The resulting beta,gamma-unsaturated silyl sulfinates can be
      desilylated and reacted with methyl iodide to provide polyfunctional sulfones.
      Exploratory studies of this four-component synthesis of sulfones are reported.
      Enantiomerically pure derivatives containing up to three new stereogenic centers
      can be obtained using enantiomerically pure (E,E)-1-alkoxy-2-methylpenta-1,3
      dienes derived from alpha-methyl benzyl alcohols, including the Greene's chiral
      auxiliary. The stereochemistry of the reactions is consistent with a mechanism
      involving the suprafacial hetero-Diels-Alder addition of sulfur dioxide to the 1
      alkoxy-1,3-dienes that are rapidly ionized into zwitterionic intermediates.

PMID- 11463261
TI  - Transmembrane ion channels constructed of cholic acid derivatives.
AB  - A new class of supramolecular transmembrane ion channels was prepared by linking
      two amphiphilic cholic acid methyl ethers through biscarbamate bonds to afford
      bis(7,12-dimethyl-24-carboxy-3-cholanyl)-N,N'-xylylene dicarbamate 2 and bis[7,12
      dimethyl-24-(N,N,N-trimethylethanaminium-2-carboxylate)-3-cholanyl]-N,N'-xylylene
      dicarbamate dichloride 3. When incorporated into a planar bilayer membrane, both
      compounds showed stable (lasting 10 ms to 10 s) single ion channel currents. Only
      limited numbers of relatively small conductances were characterized for these
      channels (5-20 pS for 2 and 5-10 pS for 3, 10 and 17 pS for 2, and 9 pS for 3 in
      particular). Both channels were cation selective, and permeability ratios of
      potassium cation to chloride anion were 17 and 7.9 for 2 and 3, respectively,
      reflecting the difference in ionic species of the headgroup. Both channels 2 and
      3 showed significant potassium selectivity over sodium by a factor of 3.1 and
      3.2, respectively. No Li(+) currents were observed for 2, showing sharp
      discrimination between Na(+) or K(+).

PMID- 11463262
TI  - Conversion of glucosamine to galactosamine and allosamine derivatives: control of
      inversions of stereochemistry at C-3 and C-4.
AB  - The reactions of sodium benzoate with a series of trimesylates derived from
      glucosamine have been examined in an attempt to gain facile access to
      galactosamine analogues. Trimesylate 17, in which the amino group was protected
      as a phthalimide, underwent double displacement at positions 4 and 6 to give the
      dibenzoate 18 with the desired galactosamine configuration. In contrast,
      trimesylates 21 and 27, in which the amino groups were protected as acetamides,
      unexpectedly underwent double displacement at positions 3 and 6, giving products
      22 and 28, respectively, with allosamine configurations.

PMID- 11463263
TI  - Synthesis of a novel bicyclic nucleoside restricted to an S-type conformation and
      initial evaluation of its hybridization properties when incorporated into
      oligodeoxynucleotides.
AB  - The phosphoramidite (1S,3R,4S)-3-(2
      cyanoethoxy(diisopropylamino)phosphinoxymethyl)-5-N-(4-monomethoxytrityl)-1
      (uracil-1-yl)-5-aza-2-oxabicyclo[2.2.1]heptane 18 of a novel bicyclic nucleoside
      structure was synthesized from the known 1-(3'-deoxy-beta-D-psicofuranosyl)uracil
      3. Conformational analysis of its structure verified its expected S-type furanose
      conformation, and the secondary amino group in the 4'-position allowed for
      incorporation into oligonucleotides using 5' --> 3' directed oligonucleotide
      synthesis as previously described for phosphoramidates. Thermal denaturation
      studies showed rather large decreases in duplex stabilities of -4.3 and -2.7
      degrees C per modification toward complementary DNA and RNA, respectively.

PMID- 11463264
TI  - Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrones.
AB  - Efficient routes to the synthesis of norbornadiene-tethered nitrones have been
      developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The
      cycloadditions occurred in moderate to good yields for a variety of substrates
      and were found to be highly regio- and stereoselective, giving single regio- and
      stereoisomers in most cases.

PMID- 11463265
TI  - Kinetics of the thiazolium ion-catalyzed benzoin condensation.
AB  - The formation of benzoin (Ph-CHOH-CO-Ph) from two molecules of benzaldehyde,
      catalyzed by 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide in methanol
      buffered with Et(3)N/Et(3)NH(+)Cl(-) has been studied. Initial-rate studies at
      various concentrations of PhCHO (0.1-1.7 M) showed that the reaction is close to
      being first order in PhCHO. Following the reaction in deuteriomethanol, (1)H NMR
      spectroscopy allowed rate constants for all three kinetically significant steps
      to be determined. These show that all three steps are partially rate-determining.
      A normal deuterium kinetic isotope effect for the overall reaction (k(H)/k(D)
      approximately 3.4) is observed using PhCDO, and a large inverse solvent isotope
      effect (k(D)/k(H) approximately 5.9) is observed using deuteriomethanol,
      consistent with the kinetic scheme presented here.

PMID- 11463266
TI  - Synthesis and solution conformational analysis of 2,3-anhydro-3-C-[(1R)-2,6
      anhydro-1-deoxy-1-fluoro-D-glycero-D-gulo-heptitol-1-C-yl]-beta-D-gulo-furanose:
      first example of a monofluoromethylene-linked C-disaccharide.
AB  - Condensation of 2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosylcarbaldehyde with
      isolevoglucosenone induced by Et(2)AlI, followed by epoxidation, gave an aldol
      that was fluorinated into a monofluoromethylene C-glucopyranoside that was
      converted into the title C-disaccharide 1. Its conformational behavior in water
      has been studied by using a combination of NMR spectroscopy (J and NOE data) and
      molecular mechanics calculations.

PMID- 11463267
TI  - Synergic effect of vicinal stereocenters in [3 + 2] cycloadditions of
      carbohydrate azadipolarophiles and mesoionic dipoles: origin of diastereofacial
      selectivity.
AB  - The intermolecular [3 + 2] cycloaddition of carbohydrate-derived 1,2-diaza-1,3
      butadienes and 1,3-thiazolium-4-olates provides a conceptual basis for the
      problem of diastereofacial preference in the acyclic series of unsaturated
      sugars. Experimental results employing a side chain of D-arabino configuration
      have shown the stereodifferentiation exerted by the first stereogenic center that
      renders the Re,Re face of the acyclic sugar-chain azadiene eligible for
      cycloaddition (J. Org. Chem. 2000, 65, 5089). The results of the present work,
      now utilizing an alternative framework of D-lyxo configuration, evidence the
      discriminating power of the second stereogenic carbon, which induces the
      preferential approach to the Re,Si face of the heterocyclic dipole. This scheme
      of face selectivity is also grounded in theoretical calculations at a
      semiempirical level. In addition to dihydrothiophenes, which are the expected
      products of the [3 + 2] cycloaddition, bicyclic systems based on
      dihydrothieno[2,3-c]piperidine skeleton can also be obtained.

PMID- 11463268
TI  - Phosphinic acid pseudopeptides analogous to glutamyl-gamma-glutamate: synthesis
      and coupling to pteroyl azides leads to potent inhibitors of folylpoly-gamma
      glutamate synthetase.
AB  - Several routes to a complex phosphinate phosphapeptide analogous to the gamma
      glutamyl peptide Glu-gamma-Glu have been investigated. Formation of gamma
      phosphono glutamate derivatives via addition of a phosphorus-based radical to
      protected vinylglycine was found to be of limited value because of the elevated
      temperatures required. Alkylation and conjugate addition reactions of trivalent
      phosphorus (P(III)) species were investigated. In situ generation of bis
      trimethylsilyl esters of phosphinous acids proved to be an effective route to
      phosphinates of modest structural complexity. However, this chemistry could not
      be extended to the incorporation of an amino acid moiety at the N-terminal side
      of the desired phosphinate. A successful synthesis of the target phosphinate
      phosphapeptide was effected using P(III) chemistry and dehydrohalogenation to
      yield an alpha,beta-unsaturated phosphinic acid ester, following which conjugate
      addition of diethylacetamido malonate and acid-mediated hydrolysis afforded the
      desired phosphinate phosphapeptide. Coupling of the unprotected phosphinate
      phosphapeptide with two acyl azides derived from folic acid and methotrexate led
      to the corresponding pteroylphosphapeptides of interest as possible mimics of
      tetrahedral intermediates in the reaction catalyzed by folylpolyglutamate
      synthetase.

PMID- 11463269
TI  - Role of hydrogen bonding in the oxidation of thianthrene 5-oxide with peroxy
      acids.
AB  - The oxidation of thianthrene 5-oxide, i.e., a mechanistic probe for the
      assessment of the electronic character of various oxidants, with peroxybenzoic
      acids in various oxygen bases as solvents was investigated. The nucleophilicity
      (X(SO)) of peroxy acids was increasing with increasing basicity of the oxygen
      base. A good linear correlation was observed by plotting X(SO) values vs either
      the Kamlet-Taft beta values or the OOH (1)H NMR chemical shifts of m
      chloroperoxybenzoic acid (m-CPBA) in solvents of various basicity. These
      observations, together with the results of IR and (1)H NMR spectroscopic studies
      of peroxybenzoic acids, and DFT (B3LYP/6-311++G) studies of the intramolecular
      hydrogen bonding in peroxyformic, peroxyacetic, and m-CPBA, as well as the
      intermolecular hydrogen bonding in the complexes of the these peroxy acids with
      dimethyl ether as a model oxygen base, support the involvement of the peroxy acid
      oxygen base complexes in the transition states of these reactions. The increased
      nucleophilicity (X(SO)) of peroxy acids in basic solvents is most likely due to
      the increased negative charge on the terminal "electrophilic" peroxycarboxylic
      oxygen atom (OH), and/or the increased LUMO and HOMO energies of the peroxy acid
      in the complexes, as compared to those parameters in the intramolecularly
      hydrogen-bonded form of peroxy acids, believed to be operative in inert solvents.

PMID- 11463270
TI  - Synthesis and evaluation of a series of C3-substituted CBI analogues of CC-1065
      and the duocarmycins.
AB  - The synthesis and evaluation of a series of C3-substituted 1,2,9,9a
      tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) analogues of the CC-1065 and
      duocarmycin alkylation subunits are detailed, including methyl and the full
      series of halogens. Introduction of the key substituent was accomplished through
      directed metalation of the seco-CBI core followed by reaction of the resultant
      aryllithium with an appropriate electrophile. C3-Bromo and iodo substituents were
      only effectively installed on the hindered aryllithium intermediate using a novel
      halogen source, 1-bromo- and 1-iodophenylacetylene, that should prove generally
      useful beyond the studies we describe. X-ray crystal structures of the series
      show substantial distortion in the vinylogous amide due to unfavorable steric
      interactions between the C3-substituent and the N(2)-carbamate. In the halogen
      series, the N2-C2a bond length and the torsional angle chi(1) smoothly increase
      with the increasing size of the C3 substituent indicative of decreasing
      vinylogous amide conjugation through the series (H > F > Cl > Br > I). Unlike N
      Boc-CBI, this series of substituted CBI analogues proved remarkably reactive
      toward solvolysis even at pH 7, where the reaction is uncatalyzed and the
      reactivity order (I > Br > Cl > F > H) follows a trend consistent with the extent
      of vinylogous amide conjugation and stabilization. The implications of these
      observations on the source of catalysis for the DNA alkylation reaction of the
      natural products are discussed.

PMID- 11463271
TI  - Organometallic dehydro[14] annulenes containing Vollhardt's cyclobutadiene: are
      CpCo-complexed cyclobutadienes more aromatic then benzene?
AB  - Pd-catalyzed coupling of 1,2-diethynyl-3,4
      (bistrimethylsilyl)cyclobutadienecyclopentadienylcobalt to a series of 1-iodo-2
      (trimethylsilylethynyl)benzenes and 1-chloro-4-trimethylsilylbut-1-ene-3-yne is
      followed by desilylation with potassium carbonate. Cu(OAc)(2)-promoted oxidative
      ring closure leads to dehydro[14]annulenes and dehydro[14]benzoannulenes fused to
      a cyclobutadiene(cyclopentadienylcobalt) complex. Five of these fused
      dehydroannulenes were structurally characterized. (1)H NMR spectroscopy of the
      organometallic dehydro[14]annulenes incorporating the
      (bistrimethylsilyl)cyclobutadiene(cyclopentadienylcobalt) unit suggested that the
      aromaticity of the fused cyclobutadiene complex might be stronger than that of
      benzene according to the ring-current criterion.

PMID- 11463272
TI  - Remote substituent effects on the oxymercuration of 2-substituted norbornenes: an
      experimental and theoretical study.
AB  - The effect of a remote substituent on regioselectivity in the oxymercuration of 2
      substituted norbornenes has been investigated experimentally and theoretically
      using density functional theory (DFT). Regioselectivities of 1:1 to 14:1 were
      observed with various 2-substituted norbornenes. Exo-2-substituted norbornenes
      always gave greater regioselectivities compared to the corresponding endo-2
      substituted norbornenes. The effects of solvents on the regioselectivity have
      also been examined, and ethereal solvents were found to be the best choice giving
      the optimal yield and regioselectivity. The relative rate of oxymercuration was
      estimated by competition experiments. The least reactive substrate (X = OAc) gave
      the highest regioselectivity. According to DFT predictions, the increased
      difference between the reaction barriers that results in the greater
      regioselectivity is correlated directly with the larger polarity of the C=C
      double bond, which is attacked by the mercury and oxygen. A number of stable exo
      and endo conformers were predicted. All exo conformers show the same polarity of
      the double bond, while some endo conformers have a reversal of this polarity. All
      the conformers except those with the OAc substituent are very close in energy and
      thus should react. The existence of a mixture of endo conformers with the C=C
      double bond of opposite polarity clearly explains a decrease in regioselectivity
      for the endo species. The origin of the greatest regioselectivity for the OAc-2
      norbornenes lies in the fact that the conformer with the largest polarity is
      notably lower in energy than others due to an internal C-H-O hydrogen bond.

PMID- 11463273
TI  - Transition states and mechanisms of the hetero-Diels-Alder reactions of
      hyponitrous acid, nitrosoalkanes, nitrosoarenes, and nitrosocarbonyl compounds.
AB  - The transition states and energetics of Diels-Alder reactions for a variety of
      nitroso compounds with dienes were explored with density functional theory using
      the B3LYP functional and 6-31G basis set. The reactions involve HNO, various
      nitrosoalkanes and arenes (RNO and ArNO), and nitrosoformaldehyde (CHONO) as
      dienophiles with butadiene and a series of 1- and 2-substituted dienes. The
      mechanisms, activation energies, energies of reaction, stereoselectivities, and
      regioselectivities are predicted for these reactions. These predictions are
      compared to available experimental data. The mechanism is found to be concerted
      but involves highly asynchronous transition states. Although it is not evident in
      the products, we find that the endo path is very strongly favored over the exo
      alternative due to repulsion between the diene and nitrogen's lone pair. A range
      of experimental regioselectivities are reproduced by calculations and are found
      to hinge on a very sensitive balance between FMO interactions, electrostatics,
      and steric effects. A series of generalizations for predicting regioselectivity
      for untried diene-dienophile pairs are made.

PMID- 11463274
TI  - Stereoselective nucleophilic formylation and cyanation of alpha-alkoxy- and alpha
      aminoaldehydes.
AB  - The spontaneous 1,2-addition of formaldehyde N,N-dialkylhydrazones to
      carbohydrate-derived alpha-alkoxyaldehydes takes place under neutral conditions
      and in the absence of catalysts or promoters to afford the corresponding alpha
      hydroxyhydrazones in good to excellent yields and with highly anti
      diastereoselectivities. Subsequent transformations of the hydrazono group into
      aldehydes and nitriles following known procedures provide a new entry into the
      homologation of carbohydrates and the synthesis of cyanohydrins, respectively.
      Additionally, reaction of methyleneaminopyrrolidine with N-Boc-protected alpha
      aminoaldehydes from natural amino acids efficiently affords the corresponding
      adducts under the same conditions. From these adducts, a variety of biologically
      interesting alpha-hydroxy-beta-aminocarbonyl compounds can be accessed upon
      manipulation of the hydrazone moiety.

PMID- 11463275
TI  - Metal-promoted allylation, propargylation, or allenylation of azetidine-2,3
      diones in aqueous and anhydrous media. Application to the asymmetric synthesis of
      densely functionalized 3-substituted 3-hydroxy-beta-lactams.
AB  - Metal-mediated carbonyl allylation, allenylation, and propargylation of optically
      pure azetidine-2,3-diones were investigated in both anhydrous and aqueous
      environments. Different metals promoters showed varied regioselectivities on
      product formation during allenylation/propargylation reactions of the keto-beta
      lactams. The stereochemistry of the new C3-substituted C3-hydroxy quaternary
      center was controlled by placing a chiral auxiliary at C4. In this way, the
      coupling of azetidine-2,3-diones with a variety of propenyl-, propynyl-, and
      allenylmetal reagents offers a convenient asymmetric entry to potentially
      bioactive 3-substituted 3-hydroxy-beta-lactams.

PMID- 11463276
TI  - Total synthesis of rutamycin B, a macrolide antibiotic from Streptomyces
      aureofaciens.
AB  - Rutamycin B (2) was synthesized from three principal subunits, spiroketal 75,
      keto aldehyde 83, and aldehyde 108. First, triol 62 was assembled by Julia
      coupling of sulfone 56 with aldehyde 58 followed by an acid-catalyzed
      spiroketalization. The three hydroxyl functions of 62 were successfully
      differentiated, leading to phosphonate 75. The latter was condensed in a
      Wadsworth-Emmons reaction with 83, prepared in six steps from (R)-aldehyde 76, to
      give 92. Coupling of the titanium enolate of 92 with 108 afforded Felkin product
      109 with high stereoselectivity in a process that is critically dependent on the
      presence of the p-methoxybenzyl ether in the aldehyde. Transformation of 109 via
      aldehyde 116 to vinylboronate 122 was followed by macrocyclization under Suzuki
      conditions to yield 123. Exhaustive desilylation of the latter yielded rutamycin
      B.

PMID- 11463277
TI  - Generation of cyclopentadienones from 2-bromocyclopentenones.

PMID- 11463278
TI  - Intramolecular cyclizations of imines bearing the 2-(thiomethyl)-3-trimethylsilyl
      1-propenyl terminator. An efficient new procedure for the stereocontrolled
      synthesis of functionalized pyrrolidine derivatives.

PMID- 11463279
TI  - Efficient synthesis of a fluorescent farnesylated Ras peptide.

PMID- 11463280
TI  - The solid state and solution structure of HAPyU.

PMID- 11463281
TI  - Acid-catalyzed hydrolysis and lactonization of alpha2,8-linked oligosialic acids.

PMID- 11463282
TI  - DFT-based quantitative prediction of regioselectivity: cycloaddition of
      nitrilimines to methyl propiolate.

PMID- 11463283
TI  - Iron-catalyzed reaction of propargyl sulfides and trimethylsilyldiazomethane.

PMID- 11463284
TI  - A facile synthesis of naturally occurring aminopeptidase inhibitor tyromycin A.

PMID- 11463285
TI  - C-H bond activation in dense carbon dioxide: rhodium-catalyzed methane
      carbonylation and alkane dehydrogenation.

PMID- 11463286
TI  - A mild procedure for the reduction of pyridine N-oxides to piperidines using
      ammonium formate.

PMID- 11463287
TI  - A straightforward synthetic entry to the 4,9b-propanopyrrolo[2,3-c]quinoline
      system by a new reductive cyclization of alpha'-(2-nitrophenyl) enones.

PMID- 11463288
TI  - Kinetics and activation parameters for the thermal 1,5-hydrogen shifts
      interconverting the four monodeuterio-cis,cis-1,3-cyclooctadienes.

PMID- 11463289
TI  - Double carbonylation of aryl iodides with primary amines under atmospheric
      pressure conditions using the Pd/PPh(3)/DABCO/THF system.

PMID- 11463290
TI  - Toward the total synthesis of variecolin.
AB  - [reaction: see text] An annulative approach toward the total synthesis of the
      sesterterpenoid variecolin (1) is presented. Synthesis of the key hemiketal,
      containing the core ABC ring skeleton, has been achieved on a model system by an
      expeditious route utilizing samarium(II) iodide. Furthermore, enantioselective
      syntheses of component fragments for the total synthesis have been developed.

PMID- 11463291
TI  - Template-directed C-H insertion: synthesis of the dioxabicyclo[3.2.1]octane core
      of the zaragozic acids.
AB  - [reaction: see text] The preparation of (+/-)-24, a model for the core of the
      zaragozic acids, is reported. The pivotal reaction in this endeavor is the
      dirhodium(II)-catalyzed intramolecular C-H bond insertion of 2-diazoacetyl-1,3
      dioxane 4, a transformation which generates four of the six stereocenters present
      in the core structure. A novel method for the diastereoselective synthesis of
      pyruvic acid acetals was also developed and employed in the preparation of 4 from
      xylitol derivative 7.

PMID- 11463292
TI  - Vinyl imidates in cycloaddition reactions: a formal synthesis of (+/-)-reserpine.
AB  - [reaction: see text] The intramolecular Diels-Alder reaction of N
      acylvinylimidates provides an efficient entry into cis-fused perhydroisoquinoline
      ring systems. This is demonstrated by the preparation of isoquinoline 2, an
      intermediate, which has been previously transformed to reserpine.

PMID- 11463293
TI  - Stereoselective synthesis of chiral 2,3-cis-2-ethynylaziridines by base-mediated
      intramolecular amination of bromoallenes.
AB  - [reaction: see text] Novel stereoselective synthesis of 2,3-cis-2
      ethynylaziridines from amino allenes is presented. While sodium hydride mediated
      intramolecular amination of (4S,aS)-4-alkyl-4-[N-(arylsulfonyl)amino]-1-bromobuta
      1,2-dienes yields a mixture of 2,3-cis- and 2,3-trans-2-ethynylaziridines in
      which the cis-isomer predominates (79:21-89:11), the amination of (4S,aR)-isomers
      affords 2,3-cis-aziridines in excellent selectivities (91:9-100:0). Conversion of
      2,3-trans-2-ethynylaziridines into the corresponding cis-isomers via a sequence
      of reactions (methanesulfonic acid mediated ring-opening reaction, bromination,
      and aziridination) is also described.

PMID- 11463294
TI  - Synthesis of a new class of 5'-functionalized adenosines using a rh(ii)-catalyzed
      1,3-dipolar cycloaddition.
AB  - [reaction: see text] Chemically protected adenosine was functionalized at the 5'
      position to generate novel dipolarophiles and mesoionic dipoles. These species
      were found to undergo facile 1,3-dipolar cycloaddition to afford a new series of
      adenosine derivatives that contain a point of diversification at the 5' position
      of adenosine.

PMID- 11463295
TI  - Bioconversion of the anthracycline analogue desacetyladriamycin by recombinant
      DoxA, a P450-monooxygenase from Streptomyces sp. strain C5.
AB  - [reaction: see text] A recombinant P450-monooxygenase, DoxA, obtained from
      Streptomyces sp. strain C5, the producer of the anticancer compound daunorubicin,
      was expressed in S. lividans TK24 and therein used to catalyze the conversion of
      the anthracycline analogue desacetyladriamycin into the new anthracycline, 10
      hydroxydesacetyladriamycin. This work establishes a new function for DoxA and
      demonstrates the use of a recombinant enzyme to prepare a new anthracycline
      analogue.

PMID- 11463296
TI  - MacDonald [2 + 2]-type condensation with vicinal diketones: synthesis and
      properties of novel spiro-tricyclic porphodimethenes.
AB  - [structure: see text] Acid-catalyzed [2 + 2] condensation reactions of polycyclic
      aromatic vicinal diketones including aceanthrenequinone, phenathrenequinone, and
      pyrene-4,5-dione with 5-mesityldipyrromethanes are outlined, and this methodology
      provides a flexible entry to spiro-tricyclic porphodimethenes. The
      porphodimethene products have been fully characterized, including X-ray structure
      analyses and fluorescence spectroscopy. In the case of the phenanthrenone
      substituted macrocycle, the two spiro-locks can be ring-opened to form a trans
      bis(2'-hydroxymethylbiphenyl)-substituted porphyrin.

PMID- 11463297
TI  - Synthesis and properties of 9,9-diarylfluorene-based triaryldiamines.
AB  - [reaction: see text] 9,9-Diaryl-2,7-dibromofluorene was synthesized by a triflic
      acid promoted Friedel-Crafts reaction. Introduction of diarylamino groups at its
      C2 and C7 positions by a Pd-catalyzed amination results in the formation of a
      novel class of triaryldiamines. The 9,9-diaryl substituents at the central
      linkage play a less important role in the photophyscial properties but affect the
      oxidation potential and improve the morphological stability of these new
      triarylamines.

PMID- 11463298
TI  - Total synthesis of nafuredin, a selective NADH-fumarate reductase inhibitor.
AB  - [structure: see text] Total synthesis of nafuredin, a selective NADH-fumarate
      reductase inhibitor, has been accomplished by a convergent approach. The C1-C8
      and C9-C18 segments were derived efficiently from D-glucose and (S)-(-)-2-methyl
      1-butanol, respectively, coupled by stereoselective Julia olefination, and
      converted to nafuredin.

PMID- 11463299
TI  - Intramolecular aminyl and iminyl radical additions to alpha,beta-unsaturated
      esters. Diastereoselective tandem cyclofunctionalization and hydrogen transfer
      reactions.
AB  - [reaction: see text] A tandem process featuring intramolecular aminyl radical
      cyclofunctionalization and hydrogen transfer affords 2,3-trans-disubstituted
      pyrrolidines with anti or syn diastereoselectivity. The extension of this
      strategy to iminyl radicals gives trans-anti pyrrolenines with high levels of 1,2
      induction in both steps of the tandem process.

PMID- 11463300
TI  - Combination of tert-butoxycarbonyl and triphenylphosphonium protecting groups in
      the synthesis of substituted hydrazines.
AB  - [structure: see text] A new reagent for the systematic synthesis of substituted
      hydrazines is reported. Unlike previously developed reagents, this one contains
      only two protecting groups, thus providing a faster approach to multisubstituted
      derivatives. The selective introduction of alkyl and acyl groups is illustrated
      by a few examples. Also a new fast method for the deprotection of the
      triphenylphosphonium group is presented.

PMID- 11463301
TI  - N-methylated 5-alkenyloxazolium salt transformations.
AB  - [reaction: see text] In the course of natural product synthetic studies, 5-(4
      pentenyl)oxazole and 5-(5-hexenyl)oxazole were N-methylated. The initial N
      methylated 5-alkenyloxazolium salt adducts were found to be only intermediates
      and were ultimately transformed into hydroindole and hydroisoquinoline compounds,
      respectively.

PMID- 11463302
TI  - SbF(5)-mediated reactions of oxafluorodiazirines.
AB  - [reaction: see text] The reaction of benzyloxyfluorodiazirine (3) with SbF(5) in
      benzene gives PhCH(2)OCF, which undergoes SbF(5)-mediated fragmentation to
      PhCH(2)(+), CO, and SbF(6)(-); the benzyl cation alkylates benzene to yield
      diphenylmethane. Phenoxyfluorodiazirine (4) reacts with SbF(5) in benzene to give
      PhOCF and (ultimately) triphenylmethane by a pathway that avoids fragmentation.

PMID- 11463303
TI  - Aspartic protease inhibitors designed from computer-generated templates bind as
      predicted.
AB  - [reaction: see text] Novel tripeptide-derived peptidomimetics 1, 7ab, and 8ab,
      inspired by templates generated by the structure-generating program GrowMol, were
      synthesized, shown to inhibit Rhizopus chinensis pepsin, and found by X-ray
      crystallography to bind to the enzyme in the GrowMol-predicted mode. Repetitive
      evaluation of the computer-generated templates for synthetic feasibility and
      optimal enzyme interactions led to the designed compounds.

PMID- 11463304
TI  - Design and synthesis of unsymmetrical peptidyl urea inhibitors of aspartic
      peptidases.
AB  - [structure: see text] The design, synthesis, and enzyme inhibition of a new class
      of aspartic peptidase inhibitors is described. Unsymmetrical ureas were designed
      from computer-generated structures. Using mechanism-based and substrate-based
      design techniques, potent pepsin inhibitors were developed and the binding mode
      was established. Two X-ray crystal structures of enzyme-bound inhibitors revealed
      a new binding mode that is closely related to the computer-generated binding
      mode.

PMID- 11463305
TI  - From peptides to non-peptide peptidomimetics: design and synthesis of new
      piperidine inhibitors of aspartic peptidases.
AB  - [reaction: see text] The 3-alkoxy-4-arylpiperidine inhibitors of aspartic
      peptidases are shown to be a new type of non-peptide peptidomimetic inhibitor.
      These piperidines can be designed from peptide-derived inhibitors by use of a
      structure-generating program but only after the enzyme active site conformation
      has been modified in a mechanistically related fashion. New enantioselective
      syntheses of 3-alkoxy-4-arylpiperidine analogues are described.

PMID- 11463306
TI  - Influence of HMPA on reducing power and reactivity of SmBr(2).
AB  - [reaction: see text] Addition of HMPA to SmBr(2) in THF produces a reactant with
      an estimated redox potential of -2.63 +/- 0.01 V (vs Ag/AgNO(3)). This powerful
      reductant is capable of reducing ketimines and alkyl chlorides at room
      temperature. Although the structure of the reductant has not been established, it
      is nonetheless a powerful addition to the arsenal of samarium-based reductants
      currently utilized.

PMID- 11463307
TI  - Asymmetric dihydroxylation of olefins using cinchona alkaloids on highly ordered
      inorganic supports.
AB  - [reaction: see text] A modified cinchona alkaloid was grafted onto a mesoporous
      molecular sieve and onto amorphous silica gel. These heterogeneous ligands were
      employed in the asymmetric dihydroxylation of olefins under Sharpless conditions.
      The supported ligands yielded equivalent enantioselectivity compared with that of
      the homogeneous system and were easily recovered and reused.

PMID- 11463308
TI  - Novel D-pi-A chromophores based on the fulvene accepting moiety.
AB  - [reaction: see text] Novel D-pi-A chromophores based on the fulvene accepting
      moiety and p-dimethylamino phenyl and 1,3-dithiole-2-ylidene donor moieties have
      been prepared. The X-ray structures of two representative derivatives have been
      determined. Examination of the UV-visible spectra and cyclic voltamperometry data
      revealed remarkable sensitivity of the electronic structure of these derivatives
      to substituents at the cyclopentadiene ring.

PMID- 11463309
TI  - Novel DMAP-catalyzed skeletal rearrangement of 5-exo-(2-hydroxy
      ethylene)oxasilacyclopentanes.
AB  - [reaction: see text] 5-exo-(Hydroxyethylene)-2-oxa-1-silacyclopentanes are found
      to undergo a novel DMAP-catalyzed skeletal rearrangement through silicon-oxygen
      exchange during acetylation to yield the corresponding 5-(2-acetoxyalkyl)-2-oxa-1
      silacyclopent-4-enes exclusively. The mechanism for this unprecedented
      rearrangement is proposed.

PMID- 11463310
TI  - Synthesis of dixanthones and poly(dixanthone)s by cyclization of 2
      aryloxybenzonitriles in trifluoromethanesulfonic acid.
AB  - [reaction: see text] Condensation of 2-fluorobenzonitriles with phenoxides
      affords 2-aryloxybenzonitriles that cyclize cleanly in trifluoromethanesulfonic
      acid at room temperature to give xanthone-iminium triflates. The C=N bond in
      these compounds is remarkably resistant to hydrolysis, but prolonged reaction
      with strong aqueous acid under vigorous conditions affords xanthones in good
      yield. The synthesis is exemplified for a novel series of polynuclear dixanthones
      and for a high molar mass polyxanthone derived from the previously unreported
      monomer 3,3'-difluoro-4,4'-biphenyldicarbonitrile.

PMID- 11463311
TI  - Efficient introduction of protected guanidines in boc solid phase peptide
      synthesis.
AB  - [reaction: see text] Reaction of primary amines with pyrazole 1 results in rapid
      and efficient guanidinylation, either in solution or on solid phase. The reaction
      affords sulfonamide-protected products required for BOC solid phase peptide
      synthesis (SPPS) in a single step under mild conditions. Incorporation of
      orthogonally protected side chain amines permits the synthesis of peptides
      containing arginine analogues, one of which could not be prepared by coupling of
      preformed amino acids.

PMID- 11463312
TI  - Regioselective nucleophilic additions to cross-conjugated dienone system bearing
      beta-fluorine: a versatile approach to highly substituted 2-cyclopentenones.
AB  - [reaction: see text] 3-Fluoro-5-methylene-2-cyclopentenone is treated with
      appropriate nucleophiles and Lewis acids to undergo regioselective 1,2-addition,
      exocyclic 1,4-addition, and endocyclic 1,4-addition, leading to 3-substituted 4
      methylene-2-cyclopentenones, 5-substituted 3-fluoro-2-cyclopentenones, and 3
      substituted 5-methylene-2-cyclopentenones in good yields, respectively.

PMID- 11463313
TI  - Synthesis of a chiral aziridine derivative as a versatile intermediate for HIV
      protease inhibitors.
AB  - [reaction: see text] Chiral aziridine derivative 1 was prepared from D-tartaric
      acid. This compound could be utilized as a common intermediate for the synthesis
      of hydroxyethylamine class HIV protease inhibitors such as saquinavir,
      amprenavir, or nelfinavir.

PMID- 11463314
TI  - N-methoxy-N-acylnitrenium ions: application to the formal synthesis of (+/-)
      desmethylamino FR901483.
AB  - [reaction: see text] The formal synthesis of (+/-)-desmethylamino FR901483 (2) is
      described. Construction of the unique azatricyclic skeleton of 2 was accomplished
      by a sequence which involved (i) preparation of dienone 7 by an N-methoxy-N
      acylnitrenium ion-induced spirocyclization, (ii) formation of 2
      azabicyclo[3.3.1]nonane 5 by the 6-(pi-exo)-exo-trig radical cyclization of 1,7
      enyne 6, and (iii) installation of the C-5 p-methoxybenzyl side chain by Lewis
      acid-mediated alkylation of silyl enol ether 18.

PMID- 11463315
TI  - Radical transfer hydrosilylation/cyclization using silylated cyclohexadienes.
AB  - [reaction: see text] A new method for mild metal-free hydrosilylation is
      described. Silylated cyclohexadienes are used as radical transfer hydrosilylating
      reagents for various double and triple bonds. A trialkylsilane is transferred
      from a cyclohexadiene moiety to an alkene. The hydrosilylation can be combined
      with a C-C bond formation as shown for the preparation of silylated cycloalkanes
      from the corresponding dienes.

PMID- 11463316
TI  - Scavenging of fluorinated N,N'-dialkylureas by hydrogen binding: a novel
      separation method for fluorous synthesis.
AB  - [reaction: see text] A dramatic solubility increase in fluorous solvents is
      observed for N,N'-di(polyfluoroalkyl)ureas when hydrogen binding complexes are
      formed with commercially available perfluoroalkanoic acid scavengers. As a case
      example, analytically pure peptides and esters are obtained using this novel
      separation method.

PMID- 11463317
TI  - A novel strategy for the synthesis of omega-functionalized perfluoroalkyl
      iodides.
AB  - [reaction: see text] The applicability of telomeric alcohols,
      H(CF(2)CF(2))(n)()CH(2)OH, for the synthesis of omega-functionalized F-alkylating
      reagents, I(CF(2)CF(2))(n-1)CH(2)OAc (6, n = 5), is demonstrated. The key steps
      of this optimized method are the "activation" of the HCF(2)- terminus in a
      lithiation process yielding olefin 2 [(Z+E)-BuCF=CF(CF(2)CF(2))(4)CH(2)OH, 86%]
      and a successive ozonation reaction in trifluoroethanol media affording ester 3b
      [CF(3)CH(2)O(2)C(CF(2)CF(2))(4)CH(2)OH, 93%]. Highly stereospecific ozone
      cleavage of the (E)-2 isomer was observed in methanol due to the competitive
      oxidation of the solvent.

PMID- 11463318
TI  - Study on the reactivity of the alkene component in ruthenium-catalyzed [2 + 2]
      cycloadditions between an alkene and an alkyne. Part 1.
AB  - [reaction: see text] The ruthenium-catalyzed [2 + 2] cycloadditions of 7
      substituted norbornadienes with an alkyne have been investigated. The
      cycloadditions were found to be highly regio- and stereoselective, giving only
      the anti-exo cycloadducts as the single regio- and stereoisomers in good yields.
      The results on the relative rate of different 7-substituted norbornadienes in the
      Ru-catalyzed [2 + 2] cycloadditions with an alkyne indicated that the reactivity
      of the alkene component decreases dramatically as the alkene becomes more
      electron deficient.

PMID- 11463319
TI  - Stereospecific synthesis of 1,2-cis glycosides by allyl-mediated intramolecular
      aglycon delivery. 2. The use of glycosyl fluorides.
AB  - [reaction: see text] Stereospecific 1,2-cis glycosylation of 2-O-allyl-protected
      glucosyl and mannosyl fluorides via a sequence of allyl isomerization, N
      iodosuccinimide-mediated tethering, and intramolecular aglycon delivery (IAD) is
      reported. The use of fluoride as anomeric leaving group is advantageous in that
      tethering efficiencies can be increased for hindered aglycon alcohols by the use
      of extended reaction times without competitive anomeric activation.
      Intramolecular glycosylation furnishes the desired alpha-glucosides and beta
      mannosides in an entirely stereoselective manner.

PMID- 11463320
TI  - LiCB(11)Me(12): a catalyst for pericyclic rearrangements.
AB  - [structure: see text] Benzene and 1,2-dichloroethane solutions of the Li(+) salt
      of the weakly coordinating anion CB(11)Me(12)(-) catalyze the rearrangement of
      cubane to cuneane, quadricyclane to norbornadiene, basketene to Nenitzescu's
      hydrocarbon, and diademane to triquinacene. The Claisen rearrangement of phenyl
      allyl ether is also strongly accelerated.

PMID- 11463321
TI  - Synthesis and chiroptical properties of optically active, regioregular
      oligothiophenes.
AB  - [reaction: see text] A series of regioregular oligothiophenes bearing chiral
      oxazoline residues have been synthesized in high yields by a stepwise synthesis
      using the Stille cross-coupling reaction. The chiroptical properties of the
      oligothiophenes up to the octamer were investigated with UV-visible and CD
      spectroscopies. The octamer showed split-type Cotton effects in chloroform as a
      good solvent in the presence of a poor solvent such as acetonitrile, while the
      lower molecular weight oligomers exhibited almost no induced CD.

PMID- 11463322
TI  - Intramolecular radical rearrangement reactions of 2-methyleneaziridines:
      application to the synthesis of substituted piperidines, decahydroquinolines, and
      octahydroindolizines.
AB  - [reaction: see text] Intramolecular 5-exo cyclization of 3-(2-methyleneaziridin-1
      yl)propyl radicals leads to the generation of a highly strained, bicyclic
      aziridinylcarbinyl radical that undergoes C-N bond fission to the ring-expanded
      aminyl radical. This methodology provides access to substituted 3
      methylenepiperidines and, by combining it with an additional 5-exo-trig
      cyclization reaction, the octahydroindolizidine skeleton.

PMID- 11463323
TI  - Oxidative ring cleavage of cyclic acetals with hypervalent tert-butylperoxy
      lambda(3)-iodanes.
AB  - [reaction: see text] Exposure of cyclic acetals to 1-tert-butylperoxy-1,2
      benziodoxol-3(1H)-one in the presence of tert-butyl hydroperoxide and potassium
      carbonate in benzene at room temperature results in oxidative ring cleavage to
      glycol monoesters via intermediate tert-butylperoxy ortho esters.

PMID- 11463324
TI  - Catalytic Meerwein-Pondorf-Verley reduction by simple aluminum complexes.
AB  - [reaction: see text] Catalytic MPV reduction was successfully carried out using
      simple aluminum precatalysts. Alkylaluminum reagents were converted to a low
      aggregation aluminum alkoxide that was highly active for the MPV reduction of
      several carbonyl substrates in high yield (50-99%) using (i)PrOH as the reducing
      agent. A high degree of cis/trans selectivity was achieved in the reduction of 2
      methylcyclohexanone (cis/trans = 20/80) by (i)PrOH. When chiral hydride sources
      were utilized in the reduction of 2-chloroacetophenone, high enantioselectivity
      (68-80% ee) was observed.

PMID- 11463325
TI  - Remote C-H activation of phenyl-substituted alkenes by BH(3).THF: mechanism and
      applications.
AB  - [reaction: see text] The hydroboration of tetrasubstituted alkenes and, in
      particular, bicyclic alkenes with BH(3).THF at 50 degrees C provides, via a
      highly stereoselective 1,2-rearrangement and a remote C-H activation, a diol in
      which the relative stereochemistry of three centers has been controlled. A
      mechanistic study provides general rules for remote C-H activation and leads to
      new synthetic applications.

PMID- 11463326
TI  - A four-step synthesis of the hydroazulene core of guanacastepene.
AB  - [reaction: see text] A concise, four-step conversion of 2-methylcyclopentenone to
      hydroazulene 2 is described. An alternative approach that led to an unexpected
      [5,5]-bicyclic carbon framework is also discussed.

PMID- 11463327
TI  - Synthesis of the amino sugar from C-1027.
AB  - [reaction: see text] The amino sugar side chain (2) from C-1027Chr was
      synthesized in 12 steps from mannose. The key reactions are an internal
      displacement by nitrogen to introduce the cis amino group at C-4 and the
      methylation of an enolate at C-5.

PMID- 11463328
TI  - The use of sulfur ylides in the synthesis of substituted indoles.
AB  - [reaction: see text] This letter describes the insertion of rhodium carbenoids
      into thioindoles. C-10 thioindoles undergo fragmentation-coupling reactions when
      exposed to rhodium carbenoids. In an analogous fashion, ketoester- and malonate
      substituted carbenoids have been found to insert into C-2 thioindoles. In
      contrast, vinylogous carbenoids were found to alkylate C-2 thioindoles at C-3.

PMID- 11463329
TI  - A novel [2 + 2] photodimerization of N-[(E)-3,4-methylenedioxycinnamoyl]dopamine
      in the solid state.
AB  - [reaction: see text] To give photoreactivity to catecholamines, N-cinnamoyl
      substituted dopamines (E)-5a-5c and O,O'-dimethyldopamines (E)-3a-3c were
      prepared under solvent-free conditions. A particularly interesting observed
      photoreactivity was that of N-[(E)-3,4-methylenedioxycinnamoyl]dopamine ((E)-5c),
      which underwent a novel type of [2 + 2] photodimerization in the solid state,
      giving exclusively a tricyclic product 8. This reaction is the first example of
      solid-state photoaddition of an alkene to the benzene ring.

PMID- 11463330
TI  - Site-specific generation of deoxyribonolactone lesions in DNA oligonucleotides.
AB  - [reaction: see text] An efficient method for the site-specific generation of 2
      deoxyribonolactone oxidative DNA damage lesions from a "photocaged" nucleoside
      analogue was developed. A nucleoside phosphoramidite bearing a C-1' nitrobenzyl
      cyanohydrin was prepared and incorporated into DNA oligonucleotides using
      automated DNA synthesis. The caged analogue, which was stable in aqueous
      solution, was converted to the 2-deoxyribonolactone lesion by UV irradiation. DNA
      containing the caged analogue and the deoxyribonolactone site were characterized
      by electrospray mass spectrometry (ES-MS).

PMID- 11463331
TI  - Synthesis of differentially substituted hexaethynylbenzenes based on tandem
      Sonogashira and Negishi cross-coupling reactions.
AB  - [reaction: see text] Synthesis of polyethynyl-substituted aromatic compounds was
      achieved efficiently by the use of the Negishi cross-coupling reaction, and this
      method, coupled with the Sonogashira reaction, was applied to the synthesis of
      differentially substituted hexaethynylbenzenes from chloroiodobenzenes.

PMID- 11463333
TI  - Isolation and characterization of two novel A20-like proteins.
AB  - The transcription factor nuclear factor kappa B (NF-kappa B) plays a pivotal role
      in inflammatory processes through induction of adhesion molecules and chemokines.
      The zinc finger molecule A20 is an important negative regulator of NF-kappa B.
      The mechanism utilized by A20 is not fully understood, but A20 has been shown to
      bind to tumour-necrosis-factor-receptor-associated factor (TRAF) molecules, which
      are necessary for pro-inflammatory cytokine signalling. We report two novel
      genes, Cezanne (cellular zinc finger anti-NF-kappa B) and TRABID (TRAF-binding
      domain), with sequence similarity to A20. Co-immunoprecipitation studies
      indicated that TRAF6 was able to interact with both Cezanne and TRABID. In
      contrast, reporter gene experiments revealed a specific ability of Cezanne to
      down-regulate NF-kappa B. It is likely, therefore, that Cezanne participates in
      the regulation of inflammatory processes.

PMID- 11463332
TI  - Nitric oxide synthases: structure, function and inhibition.
AB  - This review concentrates on advances in nitric oxide synthase (NOS) structure,
      function and inhibition made in the last seven years, during which time
      substantial advances have been made in our understanding of this enzyme family.
      There is now information on the enzyme structure at all levels from primary
      (amino acid sequence) to quaternary (dimerization, association with other
      proteins) structure. The crystal structures of the oxygenase domains of inducible
      NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other
      information in the context of this important part of the enzyme, with its binding
      sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many
      inhibitors which interact with them. The exact nature of the NOS reaction, its
      mechanism and its products continue to be sources of controversy. The role of the
      biopterin cofactor is now becoming clearer, with emerging data implicating one
      electron redox cycling as well as the multiple allosteric effects on enzyme
      activity. Regulation of the NOSs has been described at all levels from gene
      transcription to covalent modification and allosteric regulation of the enzyme
      itself. A wide range of NOS inhibitors have been discussed, interacting with the
      enzyme in diverse ways in terms of site and mechanism of inhibition, time
      dependence and selectivity for individual isoforms, although there are many
      pitfalls and misunderstandings of these aspects. Highly selective inhibitors of
      iNOS versus eNOS and neuronal NOS have been identified and some of these have
      potential in the treatment of a range of inflammatory and other conditions in
      which iNOS has been implicated.

PMID- 11463334
TI  - Cysteine residues of SNAP-25 are required for SNARE disassembly and exocytosis,
      but not for membrane targeting.
AB  - The release of neurotransmitter at a synapse occurs via the regulated fusion of
      synaptic vesicles with the plasma membrane. The fusion of the two lipid bilayers
      is mediated by a protein complex that includes the plasma membrane target soluble
      N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein (SNAP)
      receptors (t-SNAREs), syntaxin 1A and synaptosome-associated protein of 25 kDa
      (SNAP-25), and the vesicle SNARE (v-SNARE), vesicle-associated membrane protein
      (VAMP). Whereas syntaxin 1A and VAMP are tethered to the membrane by a C-terminal
      transmembrane domain, SNAP-25 has been suggested to be anchored to the membrane
      via four palmitoylated cysteine residues. We demonstrate that the cysteine
      residues of SNAP-25 are not required for membrane localization when syntaxin 1A
      is present. Analysis of the 7 S and 20 S complexes formed by mutants that lack
      cysteine residues demonstrates that the cysteines are required for efficient
      SNARE complex dissociation. Furthermore, these mutants are unable to support
      exocytosis, as demonstrated by a PC12 cell secretion assay. We hypothesize that
      syntaxin 1A serves to direct newly synthesized SNAP-25 through the Golgi
      transport pathway to the axons and synapses, and that palmitoylation of cysteine
      residues is not required for targeting, but to optimize interactions required for
      SNARE complex dissociation.

PMID- 11463335
TI  - Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)
      binding proteins in mammals.
AB  - Based on peroxin protein 5 (Pex5p) homology searches in the expressed sequence
      tag database and sequencing of large full-length cDNA inserts, three novel and
      related human cDNAs were identified. The brain-derived cDNAs coded for two
      related proteins that differ only slightly at their N-terminus, and exhibit 39.8%
      identity to human PEX5p. The shorter liver-derived cDNA coded for the C-terminal
      tetratricopeptide repeat-containing domain of the brain cDNA-encoded proteins.
      Since these three proteins specifically bind to various C-terminal peroxisome
      targeting signals in a manner indistinguishable from Pex5p and effectively
      compete with Pex5p in an in vitro peroxisome-targeting signal 1 (PTS1)-binding
      assay, we refer to them as 'Pex5p-related proteins' (Pex5Rp). In contrast to
      Pex5p, however, human PEX5Rp did not bind to Pex14p or to the RING finger motif
      of Pex12p, and could not restore PTS1 protein import in Pex5(-/-) mouse
      fibroblasts. Immunofluorescence analysis of epitope-tagged PEX5Rp in Chinese
      hamster ovary cells suggested an exclusively cytosolic localization. Northern
      blot analysis showed that the PEX5R gene, which is localized to chromosome 3q26.2
      -3q27, is expressed preferentially in brain. Mouse PEX5Rp was also delineated. In
      addition, experimental evidence established that the closest-related yeast
      homologue, YMR018wp, did not bind PTS1. Based on its subcellular localization and
      binding properties, Pex5Rp may function as a regulator in an early step of the
      PTS1 protein import process.

PMID- 11463336
TI  - Molecular modelling and experimental studies of mutation and cell-adhesion sites
      in the fibronectin type III and whey acidic protein domains of human anosmin-1.
AB  - Anosmin-1, the gene product of the KAL gene, is implicated in the pathogenesis of
      X-linked Kallmann's syndrome. Anosmin-1 protein expression is restricted to the
      basement membrane and interstitial matrix of tissues affected in this syndrome
      during development. The anosmin-1 sequence indicates an N-terminal cysteine-rich
      domain, a whey acidic protein (WAP) domain, four fibronectin type III (FnIII)
      domains and a C-terminal histidine-rich region, and shows similarity with cell
      adhesion molecules, such as neural cell-adhesion molecule, TAG-1 and L1. We
      investigated the structural and functional significance of three loss-of-function
      missense mutations of anosmin-1 using comparative modelling of the four FnIII and
      the WAP domains based on known NMR and crystal structures. Three missense
      mutation-encoded amino acid substitutions, N267K, E514K and F517L, were mapped to
      structurally defined positions on the GFCC' beta-sheet face of the first and
      third FnIII domains. Electrostatic maps demonstrated large basic surfaces
      containing clusters of conserved predicted heparan sulphate-binding residues
      adjacent to these mutation sites. To examine these modelling results anosmin-1
      was expressed in insect cells. The incorporation of the three mutations into
      recombinant anosmin-1 had no effect on its secretion. The removal of two dibasic
      motifs that may constitute potential physiological cleavage sites for anosmin-1
      had no effect on cleavage. Peptides based on the anosmin-1 sequences R254--K285
      and P504--K527 were then synthesized in order to assess the effect of the three
      mutations on cellular adhesion, using cell lines that represented potential
      functional targets of anosmin-1. Peptides (10 microg/ml) incorporating the N267K
      and E514K substitutions promoted enhanced adhesion to 13.S.1.24 rat olfactory
      epithelial cells and canine MDCK1 kidney epithelial cells (P<0.01) compared with
      the wild-type peptides. This result was attributed to the introduction of a
      lysine residue adjacent to the large basic surfaces. We predict that two of the
      three missense mutants increase the binding of anosmin-1 to an extracellular
      target, possibly by enhancing heparan sulphate binding, and that this critically
      affects the function of anosmin-1.

PMID- 11463337
TI  - Phosphorylation is a regulatory mechanism in apolipoprotein B mRNA editing.
AB  - The editing of apolipoprotein B (apoB) mRNA is under tissue-specific,
      developmental and metabolic regulation. We found that multiple protein kinase
      inhibitors or activators increased apoB mRNA editing up to 2.5-fold in Caco-2
      cells and 3-8-fold in McA7777 and FAO rat cells respectively. The phosphorylation
      agent-induced modulation is independent of the apolipoprotein B editing catalytic
      subunit 1 (APOBEC-1) and of apoB mRNA expression levels, indicating the
      involvement of a protein modification, such as phosphorylation, regulating the
      cellular editing of apoB mRNA. Transient expression of protein kinase C-&theta;
      more than doubled apoB mRNA editing in FAO cells. Chronic exposure to ethanol, a
      treatment known to increase the expression of protein kinases and to change
      protein phosphorylation status, increased apoB mRNA editing in FAO cells up to
      2.5-fold without increasing the mRNA abundance of APOBEC-1. The elimination of
      potential phosphorylation sites 47 and 72 of human APOBEC-1 decreased its
      activity to approx. one-eighth of control levels by a Ser(47)-->Ala mutation, but
      more than doubled the activity by a Ser(72)-->Ala mutation. The activity
      modulation was reversed by a Ser-->Asp mutation at sites 47 and 72, which
      introduced a phosphorylation-like carbonic acid group. Both human APOBEC-1
      dephosphorylated by alkaline phosphase and the Ser(47,72)-to-alanine double
      mutant protein demonstrated a shifted isoelectric focusing pattern compared with
      the wild type, indicating phosphorylation at these sites. Taken together, these
      results suggest that phosphorylation might be an important mechanism in the
      regulation of apoB mRNA editing.

PMID- 11463338
TI  - Identification and characterization of the STIM (stromal interaction molecule)
      gene family: coding for a novel class of transmembrane proteins.
AB  - STIM1 (where STIM is stromal interaction molecule) is a candidate tumour
      suppressor gene that maps to human chromosome 11p15.5, a region implicated in a
      variety of cancers, particularly embryonal rhabdomyosarcoma. STIM1 codes for a
      transmembrane phosphoprotein whose structure is unrelated to that of any other
      known proteins. The precise pathway by which STIM1 regulates cell growth is not
      known. In the present study we screened gene databases for STIM1-related
      sequences, and have identified and characterized cDNA sequences representing a
      single gene in humans and other vertebrates, which we have called STIM2. We
      identified a single STIM homologue in Drosophila melanogaster (D-Stim) and
      Caenorhabditis elegans, but no homologues in yeast. STIM1, STIM2 and D-Stim have
      a conserved genomic organization, indicating that the vertebrate family of two
      STIM genes most probably arose from a single ancestral gene. The three STIM
      proteins each contain a single SAM (sterile alpha-motif) domain and an unpaired
      EF hand within the highly conserved extracellular region, and have coiled-coil
      domains that are conserved in structure and position within the cytoplasmic
      region. However, the STIM proteins diverge significantly within the C-terminal
      half of the cytoplasmic domain. Differential levels of phosphorylation appear to
      account for two molecular mass isoforms (105 and 115 kDa) of STIM2. We
      demonstrate by mutation analysis and protein sequencing that human STIM2
      initiates translation exclusively from a non-AUG start site in vivo. STIM2 is
      expressed ubiquitously in cell lines, and co-precipitates with STIM1 from cell
      lysates. This association into oligomers in vivo indicates a possible functional
      interaction between STIM1 and STIM2. The structural similarities between STIM1,
      STIM2 and D-STIM suggest conserved biological functions.

PMID- 11463339
TI  - Measurement of proteases using chemiluminescence-resonance-energy-transfer
      chimaeras between green fluorescent protein and aequorin.
AB  - Homogeneous assays, without a separation step, are essential for measuring
      chemical events in live cells and for drug discovery screens, and are desirable
      for making measurements in cell extracts or clinical samples. Here we demonstrate
      the principle of chemiluminescence resonance energy transfer (CRET) as a
      homogeneous assay system, using two proteases as models, one extracellular (alpha
      thrombin) and the other intracellular (caspase-3). Chimaeras were engineered with
      aequorin as the chemiluminescent energy donor and green fluorescent protein (GFP)
      or enhanced GFP as the energy acceptors, with a protease linker (6 or 18 amino
      acid residues) recognition site between the donor and acceptor. Flash
      chemiluminescent spectra (20--60 s) showed that the spectra of chimaeras matched
      GFP, being similar to that of luminous jellyfish, justifying their designation as
      'Rainbow' proteins. Addition of the protease shifted the emission spectrum to
      that of aequorin in a time- and dose-dependent manner. Separation of the
      proteolysed fragments showed that the ratio of green to blue light matched the
      extent of proteolysis. The caspase-3 Rainbow protein was able to provide
      information on the specificity of caspases in vitro and in vivo. It was also able
      to monitor caspase-3 activation in cells provoked into apoptosis by staurosporine
      (1 or 2 microM). CRET can also monitor GFP fluor formation. The signal-to-noise
      ratio of our Rainbow proteins is superior to that of fluorescence resonance
      energy transfer, providing a potential platform for measuring agents that
      interact with the reactive site between the donor and acceptor.

PMID- 11463340
TI  - Two splice variants of Golgi-microtubule-associated protein of 210 kDa (GMAP-210)
      differ in their binding to the cis-Golgi network.
AB  - GMAP-210 (Golgi-microtubule-associated protein of 210 kDa) is a peripheral Golgi
      protein that interacts with the minus end of microtubules through its C-terminus
      and with cis-Golgi network membranes through its N-terminus; it participates in
      the maintenance of the structural integrity of the Golgi apparatus [Infante,
      Ramos-Morales, Fedriani, Bornens and Rios (1999) J. Cell Biol. 145, 83--98]. We
      report here the cloning of a new isoform of GMAP-210 that lacks amino acid
      residues 105--196. On the basis of the analysis of the gmap-210 genomic sequence,
      we propose that the small isoform, GMAP-200, arises from alternative splicing of
      exon 4 of the primary transcript. Overexpression of GMAP-200 induces
      perturbations in both the Golgi apparatus and the microtubule network that are
      similar to those previously reported for GMAP-210 overexpression. We show that
      both isoforms are able to oligomerize under overexpression conditions. Analysis
      in vitro and in vivo, with the green fluorescent protein as a marker, reveals
      that the binding of the N-terminal domain of GMAP-200 to the cis-Golgi network
      membranes is lower than that of the N-terminal domain of GMAP-210. Implications
      for the regulation of interaction between the cis-Golgi network and microtubules
      are discussed.

PMID- 11463341
TI  - A three-step kinetic mechanism for selective inhibition of cyclo-oxygenase-2 by
      diarylheterocyclic inhibitors.
AB  - Cyclo-oxygenase (COX) enzymes are the targets for non-steroidal anti-inflammatory
      drugs (NSAIDs). These drugs demonstrate a variety of inhibitory mechanisms, which
      include simple competitive, as well as slow binding and irreversible inhibition.
      In general, most NSAIDs inhibit COX-1 and -2 by similar mechanisms. A unique
      class of diarylheterocyclic inhibitors has been developed that is highly
      selective for COX-2 by virtue of distinct inhibitory mechanisms for each
      isoenzyme. Several of these inhibitors, with varying selectivity, have been
      utilized to probe the mechanisms of COX inhibition. Results from analysis of both
      steady-state and time-dependent inhibition were compared. A generalized mechanism
      for inhibition, consisting of three sequential reversible steps, can account for
      the various types of kinetic behaviour observed with these inhibitors.

PMID- 11463342
TI  - Purification, molecular cloning and mechanism of action of graminelysin I, a
      snake-venom-derived metalloproteinase that induces apoptosis of human endothelial
      cells.
AB  - Apoptosis, a programmed, physiological mode of cell death, is important in tissue
      homoeostasis. Here we report that a new metalloproteinase, graminelysin I,
      purified from Trimeresurus gramineus venom, induced apoptosis of human
      endothelial cells as examined by electrophoresis and flow cytometry. Graminelysin
      I contains only a metalloproteinase domain. It is a single-chain proteinase with
      a molecular mass of 27020 Da. cDNA sequence analysis revealed that the
      disintegrin-like and cysteine-rich domains of the putative precursor protein of
      graminelysin I are likely to be processed post-translationally, producing the
      proteinase domain (graminelysin I). Graminelysin I cleaved the alpha chain of
      fibrinogen preferentially and cleaved the beta chain either on longer incubation
      or at higher concentration. Graminelysin I inhibited the adhesion of human
      umbilical-vein endothelial cells (HUVECs) to immobilized fibrinogen and induced
      HUVECs detachment in a dose-dependent manner. These effects on HUVECs were
      abolished when graminelysin I was pretreated with EDTA. However, graminelysin I
      did not inhibit the adhesion of HUVECs to immobilized collagen. HUVECs were
      susceptible to death after treatment with graminelysin I when they were cultured
      on immobilized fibrinogen. In contrast, HUVECs were rather resistant to treatment
      with graminelysin I if they were cultured on immobilized collagen. Furthermore,
      graminelysin I induced apoptosis of HUVECs in a dose-dependent manner. Similarly,
      its apoptosis-inducing activity was blocked if it was treated with EDTA. These
      results suggest that the catalytic activity of graminelysin I on matrix proteins
      contributes to its apoptosis-inducing activity.

PMID- 11463343
TI  - Fingerprinting of polysaccharides attacked by hydroxyl radicals in vitro and in
      the cell walls of ripening pear fruit.
AB  - Hydroxyl radicals (*OH) may cause non-enzymic scission of polysaccharides in
      vivo, e.g. in plant cell walls and mammalian connective tissues. To provide a
      method for detecting the action of endogenous *OH in vivo, we investigated the
      products formed when polysaccharides were treated with *OH (generated in situ by
      ascorbate-H(2)O(2)-Cu(2+) mixtures) followed by NaB(3)H(4). Treatment with *OH
      increased the number of NaB(3)H(4)-reacting groups present in citrus pectin,
      homogalacturonan and tamarind xyloglucan. This increase is attributed partly to
      the formation of glycosulose and glycosulosuronic acid residues, which are then
      reduced back to the original (but radioactive) sugar residues and their epimers
      by NaB(3)H(4). The glycosulose and glycosulosuronic acid residues were stable for
      >16 h at 20 degrees C in ethanol or buffer (pH 4.7), but were destroyed in
      alkali. Driselase-digestion of the radiolabelled polysaccharides yielded
      characteristic patterns of (3)H-products, which included galactose and
      galacturonate from pectin, and isoprimeverose, galactose, glucose and arabinose
      from xyloglucan. Pectin yielded at least eight (3)H-labelled anionic products,
      separable by electrophoresis at pH 3.5. The patterns of radioactive products form
      useful 'fingerprints' by which *OH-attacked polysaccharides may be recognized.
      Applied to the cell walls of ripening pear (Pyrus communis) fruit, the method
      gave evidence for progressive *OH radical attack on polysaccharides during the
      softening process.

PMID- 11463344
TI  - Folding of beta pep-4 beta-sheet sandwich dimers and tetramers is influenced by
      aliphatic hydrophobic residues at the intersubunit interface.
AB  - For the designed peptide 33mer, beta pep-4, formation of beta-sheet structure
      [Ilyina, Roongta and Mayo (1997) Biochemistry 36, 5245--5250] is
      thermodynamically linked to self-association. Dimers and tetramers are stabilized
      by interactions between hydrophobic residues lying on the hydrophobic faces of
      the amphipathic monomer subunits. The present study investigates the effects on
      folding and self-association of the substitution of two key hydrophobic residues
      (Ile(20) and Val(22)) at the beta-sheet sandwich interface of beta pep-4. Single
      site (I20L, I20V, I20A, V22L, V22I and V22A; where I20L corresponds to the
      substitution of Ile(20) with leucine etc.) and double-site (I20L/V22L and
      I20V/V22I) variants have been investigated. Like parent beta pep-4, all variants
      can form dimers and tetramers. NOESY data indicate that the overall beta-sheet
      fold and intersubunit beta-strand alignments are the same in all variant
      tetramers. CD data for all variants indicate mostly beta-sheet character in
      dimers and random coil character in monomers. Only for the V22I variant is the
      beta-sheet fold stabilized in the monomer state. Pulse-field gradient NMR-derived
      diffusion coefficients, measured as a function of peptide concentration, provide
      a means for deriving the distribution of monomer, dimer and tetramer states and,
      therefore, equilibrium association constants. Relative thermodynamic stabilities,
      which vary no more than approx. 0.5 kcal/mol (where 1 kcal identical with 4.184
      kJ) from peptide to peptide, are I20V/V22I>I20V>I20L/V22L=beta pep-4 (Delta G(D)
      of 7.5 kcal/mol)=I20L=I20A>V22I>V22L>V22A for dimer formation and
      I20V>I20L/V22L>I20L>beta pep-4 (Delta G(T) of 6
      kcal/mol)>V22I>I20V/V22I>V22L>I20A>V22A for tetramer formation. For the most
      part, dimer and/or tetramer stabilities are enhanced by the presence of valine
      and leucine and are attenuated by the presence of isoleucine and alanine.

PMID- 11463345
TI  - Regulation of yeast acetohydroxyacid synthase by valine and ATP.
AB  - The first step in the common pathway for the biosynthesis of branched-chain amino
      acids is catalysed by acetohydroxyacid synthase (AHAS; EC 4.1.3.18). The enzyme
      is found in plants, fungi and bacteria, and is regulated by controls on
      transcription and translation, and by allosteric modulation of catalytic
      activity. It has long been known that the bacterial enzyme is composed of two
      types of subunit, and a similar arrangement has been found recently for the yeast
      and plant enzymes. One type of subunit contains the catalytic machinery, whereas
      the other has a regulatory function. Previously, we have shown [Pang and Duggleby
      (1999) Biochemistry 38, 5222--5231] that yeast AHAS can be reconstituted from its
      separately purified subunits. The reconstituted enzyme is inhibited by valine,
      and ATP reverses this inhibition. In the present work, we further characterize
      the structure and the regulatory properties of reconstituted yeast AHAS. High
      phosphate concentrations are required for reconstitution and it is shown that
      these conditions are necessary for physical association between the catalytic and
      regulatory subunits. It is demonstrated by CD spectral changes that ATP binds to
      the regulatory subunit alone, most probably as MgATP. Neither valine nor MgATP
      causes dissociation of the regulatory subunit from the catalytic subunit. The
      specificity of valine inhibition and MgATP activation are examined and it is
      found that the only effective analogue of either regulator of those tested is the
      non-hydrolysable ATP mimic, adenosine 5'-[beta,gamma-imido]triphosphate. The
      kinetics of regulation are studied in detail and it is shown that the activation
      by MgATP depends on the valine concentration in a complex manner that is
      consistent with a proposed quantitative model.

PMID- 11463346
TI  - Phosphorylation-mimicking glutamate clusters in the proline-rich region are
      sufficient to simulate the functional deficiencies of hyperphosphorylated tau
      protein.
AB  - The microtubule-associated tau proteins represent a family of closely related
      phosphoproteins that become enriched in the axons during brain development. In
      Alzheimer's disease (AD), tau aggregates somatodendritically in paired helical
      filaments in a hyperphosphorylated form. Most of the sites that are
      phosphorylated to a high extent in paired helical filament tau are clustered in
      the proline-rich region (P-region; residues 172--251) and the C-terminal tail
      region (C-region; residues 368--441) that flank tau's microtubule-binding
      repeats. This might point to a role of a region-specific phosphorylation cluster
      for the pathogenesis of AD. To determine the functional consequences of such
      modifications, mutated tau proteins were produced in which a P- or C-region
      specific phosphorylation cluster was simulated by replacement of serine/threonine
      residues with glutamate. We show that a phosphorylation-mimicking glutamate
      cluster in the P-region is sufficient to block microtubule assembly and to
      inhibit tau's interaction with the dominant brain phosphatase protein phosphatase
      2A isoform AB alpha C. P-region-specific mutations also decrease tau aggregation
      into filaments and decrease tau's process-inducing activity in a cellular
      transfection model. In contrast, a phosphorylation-mimicking glutamate cluster in
      the C-region is neutral with regard to these activities. A glutamate cluster in
      both the P- and C-regions induces the formation of SDS-resistant conformational
      domains in tau and suppresses tau's interaction with the neural membrane cortex.
      The results indicate that modifications in the proline-rich region are sufficient
      to induce the functional deficiencies of tau that have been observed in AD. They
      suggest that phosphorylation of the proline-rich region has a crucial role in
      mediating tau-related changes during disease.

PMID- 11463347
TI  - Effect of angiotensin II and ethanol on the expression of connexin 43 in WB rat
      liver epithelial cells.
AB  - The turnover of connexin 43 (Cx43) is very rapid in many cells and involves both
      the lysosomal and proteasomal protease pathways. Here we show that Ca(2+)
      mobilizing agonists such as angiotensin II (Ang II) can up-regulate the
      expression of Cx43 in WB rat liver epithelial cells. Vasopressin had the same
      effect in A7R5 smooth-muscle cells. The effect of Ang II was not prevented by
      pretreatment with proteasomal or lysosomal inhibitors and was associated with an
      enhanced biosynthesis of Cx43 as measured by metabolic labelling experiments. The
      accumulation of Cx43 occurred in intracellular compartments and at the cell
      surface, as determined by confocal immunofluorescence studies and by
      immunoblotting of fractions soluble and insoluble in Triton X-100. Chronic
      treatment of WB cells with ethanol inhibited Cx43 expression; this was associated
      with decreased biosynthesis of Cx43. Neither treatment with Ang II nor treatment
      with ethanol altered the levels of Cx43 mRNA. Incubation of WB cells with Ang II
      did not alter gap-junctional communication as judged by a dye-coupling assay.
      However, treatment with ethanol markedly decreased gap-junctional communication
      and this effect was diminished in Ang-II-treated cells, demonstrating that gap
      junctional communication is linked to the level of Cx43 expression. We conclude
      that Cx43 biosynthesis is regulated by Ca(2+)-mobilizing agonists and ethanol in
      WB cells. The changes in Cx43 expression might have a role in modifying the
      conduction of metabolites and second messengers between cells.

PMID- 11463348
TI  - Continuous affinity-based selection: rapid screening and simultaneous
      amplification of bacterial surface-display libraries.
AB  - A new method for continuous biopanning has been developed. We have combined the
      power of affinity chromatography with the fecundity of bacteria in a unique
      process that mimics clonal selection. Mixed populations of bacteria were applied
      to a fermenter containing the immobilized ligand of interest. Bacteria retained
      in this affinity fermenter were allowed to grow under continuous washout
      conditions, such that weakly bound organisms were selectively lost. Those
      initially rare founder bacteria expressing a receptor for the immobilized ligand
      (R+ve) were thus enriched and amplified simultaneously. From an initial culture
      containing 1 x 10(10) R-ve cells spiked with fewer than 30 R+ve bacteria (<1 in
      10(8)), final ratios of R+ve/R-ve bacteria as high as 1 in 12 were observed,
      representing an enrichment factor of 55 million-fold. This technology has
      considerable potential for rapid screening of bacterial surface-display libraries
      and in facilitating directed-evolution studies.

PMID- 11463349
TI  - Constitutive shedding of the amyloid precursor protein ectodomain is up-regulated
      by tumour necrosis factor-alpha converting enzyme.
AB  - The amyloid precursor protein (APP) of Alzheimer's disease is a transmembrane
      protein that is cleaved within its extracellular domain, liberating a soluble N
      terminal fragment (sAPP alpha). Putative mediators of this process include three
      members of the ADAM (a disintegrin and metalloprotease) family, ADAM9, ADAM10 and
      ADAM17/TACE (tumour necrosis factor-alpha converting enzyme). Tumour necrosis
      factor-alpha protease inhibitor (TAPI-1), an inhibitor of ADAMs, reduced
      constitutive and muscarinic receptor-stimulated sAPP alpha release in HEK-293
      cells stably expressing M3 muscarinic receptors. However, the former was less
      sensitive to TAPI-1 (IC(50)=8.09 microM) than the latter (IC(50)=3.61 microM),
      suggesting that these processes may be mediated by different metalloproteases.
      Constitutive sAPP alpha release was increased several-fold in cells transiently
      transfected with TACE, and this increase was proportional to TACE expression. In
      contrast, muscarinic-receptor-activated sAPP alpha release was not altered in
      TACE transfectants. TACE-dependent constitutive release of co-transfected
      APP(695) was inhibited by TAPI-1 with an IC(50) of 0.92 microm, a value
      significantly lower than the IC(50)s for inhibition of either constitutive or
      receptor-regulated sAPP alpha shedding mediated by endogenous secretases. The
      results indicate that TACE is capable of catalysing constitutive alpha-secretory
      cleavage of APP, but it is likely that additional members of the ADAM family
      mediate endogenous constitutive and receptor-coupled release of sAPP alpha in HEK
      293 cells.

PMID- 11463350
TI  - Effect of chemical modification of recombinant human acetylcholinesterase by
      polyethylene glycol on its circulatory longevity.
AB  - Post-translational modifications were recently shown to be responsible for the
      short circulatory mean residence time (MRT) of recombinant human
      acetylcholinesterase (rHuAChE) [Kronman, Velan, Marcus, Ordentlich, Reuveny and
      Shafferman (1995) Biochem. J. 311, 959--967; Chitlaru, Kronman, Zeevi, Kam,
      Harel, Ordentlich, Velan and Shafferman (1998) Biochem. J. 336, 647--658;
      Chitlaru, Kronman, Velan and Shafferman (2001) Biochem. J. 354, 613--625], which
      is one of the major obstacles to the fulfilment of its therapeutic potential as a
      bioscavenger. In the present study we demonstrate that the MRT of rHuAChE can be
      significantly increased by the controlled attachment of polyethylene glycol (PEG)
      side chains to lysine residues. Attachment of as many as four PEG molecules to
      monomeric rHuAChE had minimal effects, if any, on either the catalytic activity
      (K(m)=0.09 mM and k(cat)=3.9 x 10(5) min(-1)) or the reactivity of the modified
      enzyme towards active-centre inhibitors, such as edrophonium and di-isopropyl
      fluorophosphate, or to peripheral-site ligands, such as propidium, BW284C51 and
      even the bulky snake-venom toxin fasciculin-II. The increase in MRT of the PEG
      modified monomeric enzyme is linearly dependent, in the tested range, on the
      number of attached PEG molecules, as well as on their size. It appears that even
      low level PEG-conjugation can overcome the deleterious effect of under
      sialylation on the pharmacokinetic performance of rHuAChE. At the highest tested
      ratio of attached PEG-20000/rHuAChE (4:1), an MRT of over 2100 min was attained,
      a value unmatched by any other known form of recombinant or native serum-derived
      AChE reported to date.

PMID- 11463351
TI  - Localization, purification and specificity of the full-length membrane-bound form
      of human recombinant alpha 1,3/4-fucosyltransferase from BHK-21B cells.
AB  - Fucosyltransferase III [galactoside 3(4)-L-fucosyltransferase; EC 2.4.1.65] (FT3)
      is a Golgi type II membrane protein that catalyses the synthesis of fucosylated
      Lewis motifs that are associated with cell-adhesion events and are differentially
      expressed during cell differentiation. In the present work, the full-length
      membrane bound form of FT3 has been expressed in baby hamster kidney cells. The
      enzyme has been found in the trans-Golgi and trans-Golgi network (TGN) of the
      transfected cells, where it appeared as monomers and dimers, but not as oligomers
      with high molecular masses. Therefore oligomerization is not the basis for
      correct localization of FT3 in the Golgi. The enzyme has been purified, with a
      final yield of 2% and a total purification of 2900-fold, by DEAE-Sepharose, SP
      Sepharose, GDP-Fractogel and Superdex 200 chromatography. The purified enzyme
      showed a clear preference for the Gal beta 3GlcNAc motif in oligosaccharides
      conjugated with the hydrophobic tail (CH(2))(3)-NHCO-(CH(2))(5)-NH-biotin.
      Substitution of galactose with alpha 2-linked fucose or alpha 2,3-linked N
      acetylneuraminic acid yielded a 1.9-fold increase or a 43% decrease in activity
      respectively. The enzyme showed no activity towards asialofetuin, a glycoprotein
      containing the Gal beta 3GlcNAc acceptor motif. Therefore it has been concluded
      that the membrane-bound form of FT3 is present in the Golgi and the TGN in an
      equilibrium of monomers<-->dimers, which might fucosylate glycans from
      glycolipids, but not from glycoproteins.

PMID- 11463352
TI  - Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat
      hepatoma cells.
AB  - Aldehyde dehydrogenase (ALDH) is a family of several isoenzymes important in cell
      defence against both exogenous and endogenous aldehydes. Compared with normal
      hepatocytes, in rat hepatoma cells the following changes in the expression of
      ALDH occur: cytosolic class 3 ALDH expression appears and mitochondrial class 2
      ALDH decreases. In parallel with these changes, a decrease in the polyunsaturated
      fatty acid content in membrane phospholipids occurs. In the present study we
      demonstrated that restoring the levels of arachidonic acid in 7777 and JM2 rat
      hepatoma cell lines to those seen in hepatocytes decreases hepatoma cell growth,
      and increases class 2 ALDH activity. This latter effect appears to be due to an
      increased gene transcription of class 2 ALDH. To account for this increase, we
      examined whether peroxisome-proliferator-activated receptors (PPARs) or lipid
      peroxidation were involved. We demonstrated a stimulation of PPAR expression,
      which is different in the two hepatoma cell lines: in the 7777 cell line, there
      was an increase in PPAR alpha expression, whereas PPAR gamma expression increased
      in JM2 cells. We also found increased lipid peroxidation, but this increase
      became evident at a later stage when class 2 ALDH expression had already
      increased. In conclusion, arachidonic acid added to the culture medium of
      hepatoma cell lines is able to partially restore the normal phenotype of class 2
      ALDH, in addition to a decrease in cell growth.

PMID- 11463353
TI  - Possible mechanisms involved in the down-regulation of translation during
      transient global ischaemia in the rat brain.
AB  - The striking correlation between neuronal vulnerability and down-regulation of
      translation suggests that this cellular process plays a critical part in the
      cascade of pathogenetic events leading to ischaemic cell death. There is
      compelling evidence supporting the idea that inhibition of translation is exerted
      at the polypeptide chain initiation step, and the present study explores the
      possible mechanism/s implicated. Incomplete forebrain ischaemia (30 min) was
      induced in rats by using the four-vessel occlusion model. Eukaryotic initiation
      factor (eIF)2, eIF4E and eIF4E-binding protein (4E-BP1) phosphorylation levels,
      eIF4F complex formation, as well as eIF2B and ribosomal protein S6 kinase
      (p70(S6K)) activities, were determined in different subcellular fractions from
      the cortex and the hippocampus [the CA1-subfield and the remaining hippocampus
      (RH)], at several post-ischaemic times. Increased phosphorylation of the alpha
      subunit of eIF2 (eIF2 alpha) and eIF2B inhibition paralleled the inhibition of
      translation in the hippocampus, but they normalized to control values, including
      the CA1-subfield, after 4--6 h of reperfusion. eIF4E and 4E-BP1 were
      significantly dephosphorylated during ischaemia and total eIF4E levels decreased
      during reperfusion both in the cortex and hippocampus, with values normalizing
      after 4 h of reperfusion only in the cortex. Conversely, p70(S6K) activity, which
      was inhibited in both regions during ischaemia, recovered to control values
      earlier in the hippocampus than in the cortex. eIF4F complex formation diminished
      both in the cortex and the hippocampus during ischaemia and reperfusion, and it
      was lower in the CA1-subfield than in the RH, roughly paralleling the observed
      decrease in eIF4E and eIF4G levels. Our findings are consistent with a potential
      role for eIF4E, 4E-BP1 and eIF4G in the down-regulation of translation during
      ischaemia. eIF2 alpha, eIF2B, eIF4G and p70(S6K) are positively implicated in the
      translational inhibition induced at early reperfusion, whereas eIF4F complex
      formation is likely to contribute to the persistent inhibition of translation
      observed at longer reperfusion times.

PMID- 11463354
TI  - Knockout of mouse beta 1,4-galactosyltransferase-1 gene results in a dramatic
      shift of outer chain moieties of N-glycans from type 2 to type 1 chains in
      hepatic membrane and plasma glycoproteins.
AB  - To understand the contribution of beta 1,4-galactosyltransferase (beta 4Gal-T)-1
      to galactosylation in vivo, N-glycans of hepatic membrane glycoproteins and
      plasma glycoproteins from beta 4Gal-T1 wild-type (beta 4Gal-T1(+/+)) and beta
      4Gal-T1 knockout mice were compared. Unexpectedly, glycoproteins from the
      knockout mice were found to express considerable amounts of sialylated,
      galactosylated N-glycans. A striking contrast was that galactose residues were
      largely beta 1,4-linked to GlcNAc residues in the beta 4Gal-T1(+/+) mouse glycans
      but beta 1,3-linked in the knockout mouse glycans, thus resulting in the shift of
      the backbone structure from type 2 chain (Gal beta 1-->4GlcNAc) to type 1 chain
      (Gal beta 1-->3GlcNAc). Detailed analysis of plasma glycoproteins revealed that
      the expression of sialyl linkage in N-glycans was shifted from the Sia alpha 2-
      >6Gal to the Sia alpha 2-->3Gal, and oversialylated type 1 chains were,
      remarkably, found in the knockout mouse glycans. Thus beta 4Gal-T1 deficiency was
      primarily compensated for by beta1,3-galactosyltransferases, which resulted in
      different sialyl linkages being formed on the outer chains and altered backbone
      structures, depending on the acceptor specificities of sialyltransferases. These
      results suggest that beta 4Gal-T1 in mouse liver plays a central role in the
      synthesis of type 2 chain and is also involved in the regulation of sialylation
      of N-glycans. The knockout mice may prove useful in investigation of the
      mechanism which regulates the tissue-dependent terminal glycosylation.

PMID- 11463355
TI  - Effect of 'binary mitochondrial heteroplasmy' on respiration and ATP synthesis:
      implications for mitochondrial diseases.
AB  - Respiratory-chain-complex subunits in mitochondria are encoded by nuclear or
      mitochondrial DNA. This property might have profound implications for the
      phenotypic expression of mutations affecting oxidative phosphorylation complexes.
      The aim of this paper is to study the importance of the origin of the mutation
      (nuclear or mitochondrial) on the expression of mitochondrial defects. We have
      therefore developed theoretical models illustrating three mechanisms of nuclear
      or mitochondrial DNA mutation giving rise to a deficiency in the respiratory
      chain complex: (1) a partial deficiency, homogeneously distributed in all of the
      mitochondria; (2) a complete deficiency, only affecting some of the mitochondria
      ('binary mitochondrial heteroplasmy'); and (3) a partial deficiency, affecting
      only some of the mitochondria. We show that mutations affecting oxidative
      phosphorylation complexes will be expressed in different ways depending on their
      origins. Although the expression of nuclear or mitochondrial mutations is
      evidence of a biochemical threshold, we demonstrate that the threshold value
      depends on the origin and distribution of the mutation (homogeneous or not) and
      also on the energy demand of the tissue. This last prediction has been confirmed
      in an experimental model using hexokinase for the simulation of the energy demand
      and a variation in mitochondrial concentration. We also emphasize the possible
      role of 'binary mitochondrial heteroplasmy' in the expression of mitochondrial
      DNA mutations and thus the importance of the origin of the deficit (mutation) for
      the diagnosis or therapy of mitochondrial diseases.

PMID- 11463356
TI  - Ca(2+)/calmodulin-dependent protein kinase mediates the phosphorylation of CD44
      required for cell migration on hyaluronan.
AB  - CD44 is the principal cell surface receptor for the extracellular matrix
      glycosaminoglycan hyaluronan, and binding to this ligand underlies CD44-mediated
      cell attachment and migration. As would be expected for a widely expressed
      adhesion receptor, CD44 is subject to complex regulatory events, and mis
      regulation of the receptor has been associated with a number of disease
      pathologies, including chronic inflammatory conditions and the progression of
      metastatic tumours. In previous studies we have demonstrated that a key control
      point for this receptor is the phosphorylation of CD44 on a conserved cytoplasmic
      serine residue, Ser(325). This modification is not required for efficient ligand
      binding, but is an essential component of CD44-dependent cell migration on a
      hyaluronan substratum. To understand better the mechanism regulating CD44
      phosphorylation on Ser(325), we have generated a monoclonal antibody that
      specifically recognizes CD44 phosphorylated on Ser(325), and have developed
      assays to identify the Ser(325) kinase. We demonstrate here that CD44 is
      phosphorylated to high stoichiometry in resting cells and that Ca(2+)/calmodulin
      dependent protein kinase II is a CD44 Ser(325) kinase.

PMID- 11463357
TI  - Selenium regulation of transcript abundance and translational efficiency of
      glutathione peroxidase-1 and -4 in rat liver.
AB  - Glutathione peroxidase (GPX)1 mRNA in rat liver falls dramatically during Se
      deficiency to levels that are approx. 10% of Se-adequate levels. This regulation
      is mediated by mRNA stability, and is hypothesized to involve nonsense-mediated
      mRNA decay. mRNA levels for GPX4 and other selenoproteins are much less regulated
      by Se status. To evaluate the relative contribution of mRNA abundance versus
      translational efficiency to overall regulation of GPX1 expression, we quantified
      GPX1, GPX4 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts per
      cell in rat liver. Surprisingly, we found that GPX1 transcripts in Se deficiency
      are moderately abundant and similar in abundance to GAPDH and other selenoprotein
      mRNAs; Se supplementation increases GPX1 mRNA so that it is 30-fold higher than
      GAPDH mRNA. Translational efficiency of GPX1 mRNA is half of that of GPX4.
      Translational efficiency of GPX1 mRNA increases approx. 20-fold with Se
      supplementation and appears to switch GPX1 mRNA from nonsense-mediated
      degradation to translation. This regulatory switch can explain why GPX1
      expression is an excellent parameter for assessment of Se status.

PMID- 11463358
TI  - Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor.
AB  - The human multidrug-resistance (MDR1) P-glycoprotein (Pgp) is an ATP-binding
      cassette transporter (ABCB1) that is ubiquitously expressed. Often its
      concentration is high in the plasma membrane of cancer cells, where it causes
      multidrug resistance by pumping lipophilic drugs out of the cell. In addition,
      MDR1 Pgp can transport analogues of membrane lipids with shortened acyl chains
      across the plasma membrane. We studied a role for MDR1 Pgp in transport to the
      cell surface of the signal-transduction molecule platelet-activating factor
      (PAF). PAF is the natural short-chain phospholipid 1-O-alkyl-2-acetyl-sn-glycero
      3-phosphocholine. [(14)C]PAF synthesized intracellularly from exogenous
      alkylacetylglycerol and [(14)C]choline became accessible to albumin in the
      extracellular medium of pig kidney epithelial LLC-PK1 cells in the absence of
      vesicular transport. Its translocation across the apical membrane was greatly
      stimulated by the expression of MDR1 Pgp, and inhibited by the MDR1 inhibitors
      PSC833 and cyclosporin A. Basolateral translocation was not stimulated by
      expression of the basolateral drug transporter MRP1 (ABCC1). It was insensitive
      to the MRP1 inhibitor indomethacin and to depletion of GSH which is required for
      MRP1 activity. While efficient transport of PAF across the apical plasma membrane
      may be physiologically relevant in MDR1-expressing epithelia, PAF secretion in
      multidrug-resistant tumours may stimulate angiogenesis and thereby tumour growth.

PMID- 11463359
TI  - Phorbol ester-induced activation of mitogen-activated protein
      kinase/extracellular-signal-regulated kinase kinase and extracellular-signal
      regulated protein kinase decreases glucose-6-phosphatase gene expression.
AB  - Glucose-6-phosphatase (G6Pase) plays a central role in blood glucose
      homoeostasis, and insulin suppresses G6Pase gene expression by the activation of
      phosphoinositide 3-kinase (PI 3-kinase). Here, we show that the phorbol ester PMA
      decreases both basal and dexamethasone/cAMP-induced expression of a luciferase
      gene under the control of the G6Pase promoter in transiently transfected H4IIE
      hepatoma cells. This regulation was suppressed by the inhibitors of the mitogen
      activated protein kinase/extracellular-signal-regulated kinase kinase (MEK),
      PD98059 and U0126, but not by the inhibitor of PI 3-kinase, LY294002. The co
      expression of a constitutively active mutant of MEK mimicked the regulation of
      G6Pase promoter activity by PMA. The effect of PMA on both basal and induced
      G6Pase gene transcription was impaired by the overexpression of a dominant
      negative MEK construct, as well as by the expression of mitogen-activated protein
      kinase phosphatase-1. The mutation of the forkhead-binding sites within the
      insulin-response unit of the G6Pase promoter, which decreases the effect of
      insulin on G6Pase gene expression, did not alter the regulation of gene
      expression by PMA. The data show that PMA decreases G6Pase gene expression by the
      activation of MEK and extracellular-signal regulated protein kinase. With that,
      PMA mimics the effect of insulin on G6Pase gene expression by a different
      signalling pathway.

PMID- 11463360
TI  - Type-1 ribosome-inactivating protein from iris (Iris hollandica var. Professor
      Blaauw) binds specific genomic DNA fragments.
AB  - The capacity of IRIP, a type-1 ribosome-inactivating protein (RIP) isolated from
      the bulbs of Iris hollandica, to bind specific DNA sequences from a mixture of
      approx. 200 bp (average length) fragments of total genomic DNA from Iris genome
      was studied. Fragments that were preferentially bound by IRIP were enriched by
      several cycles of affinity binding and PCR, and were cloned and sequenced. The
      selected DNA fragments do not share conserved sequences, indicating that IRIP
      does not bind DNA fragments in a strictly sequence-specific manner. According to
      sequence analysis, most IRIP-bound fragments contain one or more possible free
      energy-stable hairpin structure(s) in their secondary structure, which may be the
      basis for recognition between IRIP and these DNA fragments. Some, but not all,
      DNA fragments moderately lower the RNA N-glycosidase activity of IRIP towards
      rabbit reticulocyte lysate ribosomes. IRIP does not remove adenines from the
      binding fragments, which implies that it does not act as a
      polynucleotide:adenosine glycosidase towards these DNA fragments. The selective
      binding of IRIP to conspecific DNA fragments is also discussed in view of the
      novel concept that RIPs may act as DNA-binding proteins with a regulatory
      activity on gene expression.

PMID- 11463361
TI  - Treatment of PC12 cells with nerve growth factor increases iron uptake.
AB  - Phaeochromocytoma PC12 cells treated with nerve growth factor (NGF) differentiate
      into a neuronal phenotype. Here we compare the uptake of transferrin-bound and
      non-transferrin-bound iron in NGF-treated (neuronal phenotype) and control
      (proliferating) PC12 cells. The non-transferrin-bound iron uptake was greater in
      the NGF-treated cells than in the control, independently of the uptake time, the
      iron-chelating agents used, the oxidation state of iron (Fe(2+) or Fe(3+)) and
      the iron concentration tested. The NGF-treated cells expressed L-type and N-type
      voltage-operated Ca(2+) channels. Nitrendipine (an L-type inhibitor) and possibly
      omega-conotoxin (an N-type inhibitor) inhibited the iron uptake by 20%.
      Thapsigargin inhibits the endoplasmic reticulum Ca(2+) pump and allowed Mn(2+)
      entry into cells. Preincubating PC12 cells with thapsigargin increased the iron
      uptake. The rate of transferrin-bound iron uptake was less than 1% of the non
      transferrin-bound iron uptake and the maximum transferrin-bound iron uptake was
      also very low. We conclude that an increase in the iron uptake by multiple
      pathways accompanies the transition of PC12 cells from the proliferating to the
      neuronal phenotype.

PMID- 11463362
TI  - Sensitivity of respiratory chain activities to lipid peroxidation: effect of
      vitamin E deficiency.
AB  - Rats fed a vitamin E-depleted diet for 48 weeks had undetectable levels of
      vitamin E in the gastrocnemius muscle and liver, leading to elevated
      malondialdehyde levels in both tissues and an elevated GSH level in muscle.
      Skeletal-muscle mitochondria showed decreased mitochondrial respiratory chain
      (MRC) activities, whereas liver MRC activities were increased. Exposure of normal
      rat liver submitochondrial particles (SMPs) to an in vitro NADPH-dependent lipid
      peroxidation system resulted in a dose-dependent increase in lipid peroxidation
      and inhibition of complex I and complex IV activities. Complex I exhibited
      greater sensitivity to lipid peroxidation than complex IV. At low and high NADPH
      concentrations, the rate of lipid peroxidation and the level of enzyme inhibition
      were essentially the same in liver SMPs from both vitamin E-deficient and control
      rats, suggesting that under these conditions, the loss of vitamin E did not
      exacerbate the effects of either lipid peroxidation or enzyme inhibition. These
      results indicate that normal vitamin E levels in liver mitochondria are not
      required for protection against lipid peroxidation and are consistent with the
      normal liver mitochondrial function in vitamin E-deficient animals. This suggests
      other antioxidants, such as ubiquinol and GSH, may be more important in
      protecting liver mitochondria and MRC from lipid peroxidation.

PMID- 11463363
TI  - Ca(2+) stabilizes the semiquinone radical of pyrroloquinoline quinone.
AB  - Spectroelectrochemical studies were performed on the interaction between Ca(2+)
      and pyrroloquinoline quinone (PQQ) in soluble glucose dehydrogenase (sGDH) and in
      the free state by applying a mediated continuous-flow column electrolytic
      spectroelectrochemical technique. The enzyme forms used were holo-sGDH (the holo
      form of sGDH from Acinetobacter calcoaceticus) and an incompletely reconstituted
      form of this, holo-X, in which the PQQ-activating Ca(2+) is lacking. The
      spectroelectrochemical and ESR data clearly demonstrated the generation of the
      semiquinone radical of PQQ in holo-sGDH and in the free state in the presence of
      Ca(2+). In contrast, in the absence of Ca(2+) no semiquinone was observed, either
      for PQQ in the free state (at pH 7.0) or in the enzyme (holo-X). Incorporation of
      Ca(2+) into the active site of holo-X, yielding holo-sGDH, caused not only
      stabilization of the semiquinone form of PQQ but also a negative shift (of 26.5
      mV) of the two-electron redox potential, indicating that the effect of Ca(2+) is
      stronger on the oxidized than on the reduced PQQ. Combining these data with the
      observations on the kinetic and chemical mechanisms, it was concluded that the
      strong stimulating effect of Ca(2+) on the activity of sGDH can be attributed to
      facilitation of certain kinetic steps, and not to improvement of the
      thermodynamics of substrate oxidation. The consequences of this conclusion are
      discussed for the oxidative as well as for the reductive part of the reaction of
      sGDH.

PMID- 11463364
TI  - Angiotensin II-responsive element is the insulin-responsive element in the
      adipocyte fatty acid synthase gene: role of adipocyte determination and
      differentiation factor 1/sterol-regulatory-element-binding protein 1c.
AB  - We have previously shown that angiotensin II (Ang II) increases the expression of
      the gene encoding adipocyte fatty acid synthase (FAS). Here we investigate the
      mechanism responsible for increased FAS gene transcription by Ang II. We
      demonstrate that Ang II increased luciferase activity by 3-fold in 3T3-L1
      adipocytes transfected with fusion constructs linking the FAS promoter to the
      luciferase reporter gene. Interestingly, we mapped the Ang II regulatory
      sequences to the insulin-responsive region (E box) in the proximal FAS promoter.
      The E box alone was able to mediate Ang II responsiveness when linked to a
      heterologous promoter. However, this response was lost when mutations that
      abolished the binding of the E box to its transcription factors were introduced.
      Using adenoviral overexpression of a dominant-negative form of adipocyte
      determination and differentiation factor 1 (ADD1), a transcription factor that
      binds to the insulin-responsive E box, we demonstrated that ADD1 was required for
      Ang II regulation of the FAS gene in 3T3-L1 adipocytes. Furthermore, ADD1
      expression was also up-regulated by Ang II. With the use of transfections as well
      as glucose transport assays, we further demonstrated that Ang II stimulation of
      the FAS gene was dependent on glucose. In conclusion, this is the first report
      that Ang II regulates adipocyte FAS gene transcription via insulin response
      sequences in a glucose-dependent manner and that this regulation is mediated at
      least in part via the ADD1 transcription factor.

PMID- 11463365
TI  - Inositol lipids are regulated during cell cycle progression in the nuclei of
      murine erythroleukaemia cells.
AB  - Previous data suggest the existence of discrete pools of inositol lipids, which
      are components of a nuclear phosphoinositide (PI) cycle. However, it is not known
      whether the contents of these pools are regulated during cell proliferation. In
      the present study we demonstrate that the mass levels of three important
      constituents of the nuclear PI cycle are regulated during the cell cycle.
      Radioactive label incorporation into PtdIns(4,5)P(2) was seen to increase
      dramatically as synchronized cells entered S-phase. This did not coincide with
      any significant changes in the nuclear mass levels of this lipid, suggesting that
      the rate of turnover of this molecule was increased. Levels of PtdIns4P, the
      major substrate for PtdIns(4,5)P(2) production by Type I PtdInsP kinases
      (PIPkins), were regulated during the cell cycle and indicated a complex
      relationship between these two lipids. An alternative substrate for
      PtdIns(4,5)P(2), PtdIns5P, phosphorylated by Type II PIPkins, was present in
      nuclei at much smaller amounts than the PtdIns4P, and thus is unlikely to
      contribute significantly to PtdIns(4,5)P(2) turnover. However, a large increase
      in nuclear PtdIns5P mass was observed when murine erythroleukaemia cells are in
      G(1), and this could represent a potential pool of nuclear inositol lipid that
      has a specific signalling role. Analysis of extracted lipid fractions indicated
      the absence of any PtdIns3P in these nuclei.

PMID- 11463366
TI  - New international guidelines for chronic obstructive pulmonary disease.

PMID- 11463367
TI  - Weaning children from mechanical ventilation: a prospective randomized trial of
      protocol-directed versus physician-directed weaning.
AB  - OBJECTIVE: Compare outcomes between physician-directed and protocol-directed
      weaning from mechanical ventilation in pediatric patients. DESIGN: Prospective
      randomized. SETTING: Pediatric and cardiac intensive care units in a 307-bed
      tertiary referral hospital for children. INTERVENTIONS: The control group
      (physician-directed) was weaned according to individual physician order for
      reduction in minute ventilation, positive end-expiratory pressure, and ordered
      oxygen saturation parameters for reduction in fraction of inspired oxygen
      (F(IO)(2)). The study group (protocol-directed) was weaned according to a
      predetermined algorithm developed for the purpose of this investigation. METHODS:
      The study enrolled 223 patients (116 physician-directed, 107 protocol-directed).
      All patients were monitored for hemodynamics, ventilator parameters, arterial
      blood gas values when available, oxygen saturation, weaning time, pre-weaning
      time, extubation time, and time on F(IO)(2) > or = 0.40. We also monitored the
      incidence of reintubation, subglottic stenosis, tracheitis, and pneumonia. The
      protocol-directed group had additional measurements of actual versus predicted
      minute volume, comparisons of respiratory rate (actual versus predicted for age),
      and presence of spontaneous breathing effort for 10 consecutive minutes. Data
      analysis was done according to intent to treat. RESULTS: There was no significant
      difference in 12-hour and 24-hour pediatric risk of mortality (PRISM III) scores
      between groups. The protocol-directed group overall had shorter total ventilation
      time, weaning time, pre-weaning time, time to extubation, and time on F(IO)(2)
      >0.40, although after stratification for respiratory diagnosis, only the
      difference in weaning time remained significant. There was no difference in the
      incidence of reintubation, new-onset tracheitis, subglottic stenosis, or
      pneumonia. CONCLUSIONS: Protocol-directed weaning resulted in a shorter weaning
      time than physician-directed weaning in these pediatric patients.

PMID- 11463368
TI  - A comparison of two airway suctioning frequencies in mechanically ventilated,
      very-low-birthweight infants.
AB  - INTRODUCTION: Endotracheal suctioning of mechanically ventilated, very-low
      birthweight infants for removal of respiratory secretions can be associated with
      morbidity. Routine endotracheal suctioning is inadvisable, but the safe minimum
      endotracheal suctioning frequency for prevention of airway obstruction has not
      been determined. HYPOTHESIS: Decreasing suctioning frequency from every 4 hours
      to every 8 hours (plus as needed) would have no clinically important effect on
      the primary outcomes (nosocomial bloodstream infection [BSI], ventilator
      associated pneumonia [VAP], and bacterial airway colonization) or secondary
      outcomes (reintubation rates, need for postural drainage, severity of
      bronchopulmonary dysplasia [BPD], neonatal mortality, duration of mechanical
      ventilation, and duration of hospitalization). METHODS: We conducted a sequential
      retrospective study of 90 very-low-birthweight infants who were mechanically
      ventilated for longer than 7 days and who underwent endotracheal suctioning every
      4 hours (plus as needed) and 90 similar infants who underwent endotracheal
      suctioning every 8 hours (plus as needed). Two-pass endotracheal suctioning used
      during the study period required predetermined measurement of the suction
      catheter and prior instillation of saline. RESULTS: The 2 treatment groups were
      similar in demographic and clinical characteristics, including survival (90% and
      85%), age at time of death (28 and 33 d), mean birthweight (926 and 934 g),
      gestational age (27 and 27 wk), duration of ventilation (29 and 27 d), and
      duration of stay (55 and 53 d). Regardless of suctioning frequency, airway
      colonization with Gram-positive cocci occurred in the majority of patients by 2
      weeks of life. Forty-three percent of the infants suctioned every 4 hours and 44%
      of those suctioned every 8 hours became airway colonized with Gram-negative
      bacilli. No Gram-negative bacilli species was more likely to be associated with
      either treatment group. VAP was diagnosed in 5 of the infants suctioned every 4
      hours and in 9 of the infants suctioned every 8 hours. Nosocomial BSI occurred in
      18 of the infants suctioned every 4 hours and in 21 of the infants suctioned
      every 8 hours. The difference in incidence of VAP and BSI was due to a epidemic
      that started before the change in suctioning frequency. During hospitalization,
      approximately one fourth of the patients in each group required postural drainage
      and were reintubated 11 and 10 times per 100 ventilator days, respectively. A
      comparable number of infants in each group developed severe BPD and were
      discharged home on oxygen. Suctionings per patient per ventilator day were 6 for
      the group suctioned every 4 hours and 4 for the group suctioned every 8 hours (p
      < 0.01). CONCLUSIONS: A low-frequency suctioning regimen (every 8 hours plus as
      needed) can be implemented without increasing the incidence of nosocomial BSI,
      VAP, bacterial airway colonization, frequency of reintubation, need for postural
      drainage, severity of BPD, neonatal mortality, duration of mechanical
      ventilation, or duration of hospitalization. Although the minimum suctioning
      frequency for removal of unwanted respiratory secretions is yet to be
      established, a substantial reduction in endotracheal suctioning frequency appears
      to be safe.

PMID- 11463369
TI  - An evaluation of ventilator reliability: a multivariate, failure time analysis of
      5 common ventilator brands.
AB  - INTRODUCTION: Mechanical ventilator failures expose patients to unacceptable
      risks and are expensive. By identifying factors that correlate with the amount of
      time between consecutive ventilator failures, we might reduce patient risk, save
      money, and shed light on a number of important questions concerning whether
      reliability changes as a function of time. OBJECTIVE: Investigate the correlation
      between several explanatory variables and the time between consecutive ventilator
      failures and address the following questions: (1) Are ventilators as safe and
      reliable following repairs as they were before failing? (2) Does reliability
      change significantly as a ventilator is used or ages? (3) Does a hospital's
      particular operating environment play a role in ventilator reliability? (4) Are
      ventilator service contracts worth the money? METHODS: A retrospective review was
      conducted using repair and maintenance records from 2 hospitals: a 570-bed
      teaching hospital and a 410-bed local community hospital. Records were examined
      from a total of 66 individual ventilators, of 5 different brands, used between
      July 1, 1991, and January 3, 2001. The ventilators included 13 Tyco-Mallinckrodt
      Infant Star, 10 Bird VIP, 11 Bird 6400ST, 16 Bird 8400STi, and 16 Tyco
      Mallinckrodt 7200ae. The dependent variable was the operating time between or
      before unexpected mechanical failures; this was determined by the difference
      between hours logged on the ventilator hour meter at the time of failure and that
      recorded when the study began, or when the ventilator was new. Thereafter (when
      applicable), the time before failure was the difference in hours at consecutive
      failures. Seven independent explanatory covariates were selected and analyzed as
      potential correlates with time between failures. Another independent variable,
      the site of ventilator use (community or teaching hospital), was also tested for
      significance. Data were analyzed using the Cox proportional hazard model, the
      multiple-groups survival statistic, and the Cox-Mantel test. RESULTS: In
      2,567,365 hours of ventilator operation, 290 observations were recorded (226
      failures and 64 censored observations). Two of the 7 covariates were judged time
      dependent, excluded from the Cox model, and evaluated using other techniques. Of
      the 5 remaining covariates, 2 were significantly related to reliability, both
      indirectly. There was no difference in reliability, regardless of how many times
      a ventilator had been previously repaired, but hospital environment did
      significantly affect reliability. CONCLUSIONS: Ventilator reliability depends on
      a number of factors. This study indicates that, on average, ventilator
      reliability improves the more a ventilator is used and the longer the brand has
      been commercially available. The number of previous ventilator repairs did not
      affect reliability, but the hospital environment did. These data, if validated,
      should help to enhance our understanding of ventilator reliability and could
      eventually have profound economic and safety implications as well.

PMID- 11463370
TI  - Global strategy for the diagnosis, management, and prevention of chronic
      obstructive pulmonary disease: National Heart, Lung, and Blood Institute and
      World Health Organization Global Initiative for Chronic Obstructive Lung Disease
      (GOLD): executive summary.

PMID- 11463371
TI  - The C. elegans E2F- and DP-related proteins are required for embryonic asymmetry
      and negatively regulate Ras/MAPK signaling.
AB  - Early C. elegans embryos exhibit protein asymmetries that allow rapid
      diversification of cells. Establishing these asymmetries requires the novel
      protein MEX-5. We show that mutations in the efl-1 and dpl-1 genes cause defects
      in protein localization resembling defects caused by mutations in mex-5. efl-1
      and dpl-1 encode homologs of vertebrate E2F and DP proteins that regulate
      transcription as a heterodimer. efl-1 and dpl-1 mutants have elevated levels of
      activated Map kinase in oocytes. Their mutant phenotype and that of mex-5 mutants
      can be suppressed by reducing Ras/Map kinase signaling. We propose this signaling
      pathway has a role in embryonic asymmetry and that EFL-1/DPL-1 control the level
      of Map kinase activation.

PMID- 11463372
TI  - dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in C.
      elegans vulval development.
AB  - The synthetic multivulva (synMuv) genes define two functionally redundant
      pathways that antagonize RTK/Ras signaling during Caenorhabditis elegans vulval
      induction. The synMuv gene lin-35 encodes a protein similar to the mammalian
      tumor suppressor pRB and has been proposed to act as a transcriptional repressor.
      Studies using mammalian cells have shown that pRB can prevent cell cycle
      progression by inhibiting DP/E2F-mediated transcriptional activation. We
      identified C. elegans genes that encode proteins similar to DP or E2F. Loss-of
      function mutations in two of these genes, dpl-1 DP and efl-1 E2F, caused the same
      vulval abnormalities as do lin-35 Rb loss-of-function mutations. We propose that
      rather than being inhibited by lin-35 Rb, dpl-1 DP and efl-1 E2F act with lin-35
      Rb in transcriptional repression to antagonize RTK/Ras signaling during vulval
      development.

PMID- 11463373
TI  - Restriction of mesendoderm to a single blastomere by the combined action of SKN-1
      and a GSK-3beta homolog is mediated by MED-1 and -2 in C. elegans.
AB  - The endoderm and much of the mesoderm arise from the EMS cell in the four-cell C.
      elegans embryo. We report that the MED-1 and -2 GATA factors specify the entire
      fate of EMS, which otherwise produces two C-like mesectodermal progenitors. The
      meds are direct targets of the maternal SKN-1 transcription factor; however,
      their forced expression can direct SKN-1-independent reprogramming of non-EMS
      cells into mesendodermal progenitors. We find that SGG-1/GSK-3beta kinase acts
      both as a Wnt-dependent activator of endoderm in EMS and an apparently Wnt
      independent repressor of the meds in the C lineage, indicating a dual role for
      this kinase in mesendoderm development. Our results suggest that a broad tissue
      territory, mesendoderm, in vertebrates has been confined to a single cell in
      nematodes through a common gene regulatory network.

PMID- 11463374
TI  - Delta/Notch and Boss/Sevenless signals act combinatorially to specify the
      Drosophila R7 photoreceptor.
AB  - The R7 photoreceptor, a unique cell type within the Drosophila ommatidium, was
      initially proposed to be specified by two distinct signals from neighboring
      cells, one from the R8 photoreceptor and another from the R1/6 photoreceptor
      pair. The R8-to-R7 signal is the transmembrane ligand Bride of Sevenless (Boss),
      which is received by the receptor tyrosine kinase Sevenless (Sev) and transduced
      via Ras activation within the presumptive R7 cell. However, the identity of the
      R1/6-to-R7 signal has remained elusive. Here, we present evidence that the
      transmembrane ligand Delta (Dl), expressed by the R1/6 pair, activates the
      receptor Notch (N) in the presumptive R7 cell and constitutes the postulated R1/6
      to-R7 signal required in combination with the Boss/Sev signal to specify the R7
      fate.

PMID- 11463375
TI  - Yb modulates the divisions of both germline and somatic stem cells through piwi-
      and hh-mediated mechanisms in the Drosophila ovary.
AB  - The coordinated division of distinctive types of stem cells within an organ is
      crucial for organogenesis and homeostasis. Here we show genetic interactions
      among fs(1)Yb (Yb), piwi, and hedgehog (hh) that regulate the division of both
      germline stem cells (GSCs) and somatic stem cells (SSCs), the two constituent
      stem cell populations of the Drosophila ovary. Yb is required for both GSC and
      SSC divisions; loss of Yb function eliminates GSCs and reduces SSC division,
      while Yb overexpression increases GSC number and causes SSC overproliferation. We
      also show that Yb acts via the piwi- and hh-mediated signaling pathways that
      emanate from the same signaling cells to control GSC and SSC division,
      respectively. hh signaling also has a minor effect in GSC division.

PMID- 11463376
TI  - Late arrest of spermiogenesis and germ cell apoptosis in mice lacking the TBP
      like TLF/TRF2 gene.
AB  - Metazoan genomes encode two related proteins, TBP and the TBP-like factor
      (TLF/TRF2), sharing a highly conserved saddle-like domain. TLF is highly
      expressed in a finely regulated pattern in the mouse testis during
      spermatogenesis. The murine TLF gene has been inactivated using homologous
      recombination. TLF-/- mice are viable, but mutant male mice are sterile due to a
      late, complete arrest of spermiogenesis. In mutant animals, spermatogonia and
      spermatocytes develop normally, but round spermatids undergo apoptosis at step 7.
      Although the expression of the transcriptional activator CREM and many other
      postmeiotic genes was unaltered in TLF null mice, several spermiogenesis genes
      transcribed in late round spermatids appeared to be under TLF control. Hence, TLF
      is not required for embryonic development in the mouse but is essential for
      spermiogenesis.

PMID- 11463377
TI  - Cooperation between STAT3 and c-jun suppresses Fas transcription.
AB  - Decreased Fas expression during tumor progression often results in a loss of Fas
      ligand (FasL)-mediated apoptosis. Human and mouse melanoma exhibit an inverse
      correlation between the degree of Fas cell surface expression, tumorigenicity,
      and metastatic capacity. The expression of dominant negative Stat3 or c-Jun in
      melanoma cells efficiently increased Fas expression and sensitized cells to FasL
      induced apoptosis. Stat3+/- as well as c-Jun-/- cells exhibited increased Fas
      cell surface expression and higher sensitivity to FasL-mediated apoptosis.
      Suppression of Fas expression by Stat3 and c-Jun is uncoupled from Stat3-mediated
      transcriptional activation. Our findings indicate that Stat3 oncogenic activities
      could also be mediated through its cooperation with c-Jun, resulting in
      downregulation of Fas surface expression, which is implicated in the tumor's
      ability to resist therapy and metastasize.

PMID- 11463378
TI  - A transient histone hyperacetylation signal marks nucleosomes for remodeling at
      the PHO8 promoter in vivo.
AB  - Chromatin remodeling of the yeast PHO8 promoter requires the SAGA histone
      acetyltransferase complex. We report here that SAGA is necessary and sufficient
      to establish an activator-dependent hyperacetylation peak over the PHO8 promoter
      that is restricted to those nucleosomes that are remodeled upon activation. This
      local hyperacetylated state is observed upon activation in the absence of the
      SWI/SNF complex when the remodeling process is frozen subsequent to activator
      binding. Hyperacetylation is lost, however, if remodeling is permitted to go to
      completion. Thus, a transient histone hyperacetylation signal is shown to be a
      prerequisite for, and determinant of, the domain of nucleosome remodeling in
      vivo.

PMID- 11463379
TI  - A positioned nucleosome on the human U6 promoter allows recruitment of SNAPc by
      the Oct-1 POU domain.
AB  - The human snRNA promoters contain a proximal sequence element (PSE) required for
      basal transcription and a distal sequence element (DSE) required for activated
      transcription. The PSE recruits the multisubunit factor SNAPc, whereas the DSE
      recruits Oct-1. Oct-1 and SNAPc bind cooperatively to DNA when their respective
      binding sites are moved into proximity through a mechanism that involves a
      defined protein-protein contact. Here, we show that on the natural U6 promoter,
      cooperative binding of Oct-1 and SNAPc is mediated by a positioned nucleosome
      that resides between the DSE and the PSE. This cooperative binding requires the
      same protein-protein contact as cooperative binding to closely spaced sites on
      naked DNA and mediates transcription activation.

PMID- 11463380
TI  - CREB binding protein recruitment to the transcription complex requires growth
      factor-dependent phosphorylation of its GF box.
AB  - Growth factors such as epidermal growth factor (EGF) and insulin regulate
      development and metabolism via genes containing both POU homeodomain (Pit-1) and
      phorbol ester (AP-1) response elements. Although CREB binding protein (CBP)
      functions as a coactivator on these elements, the mechanism of transactivation
      was previously unclear. We now demonstrate that CBP is recruited to these
      elements only after it is phosphorylated at serine 436 by growth factor-dependent
      signaling pathways. In contrast, p300, a protein closely related to CBP that
      lacks this phosphorylation site, binds only weakly to the transcription complex
      and in a growth factor-independent manner. A small region of CBP (amino acids 312
      440), which we term GF box, contains a potent transactivation domain and mediates
      this effect. Direct phosphorylation represents a novel mechanism controlling
      coactivator recruitment to the transcription complex.

PMID- 11463381
TI  - Selective insulin signaling through A and B insulin receptors regulates
      transcription of insulin and glucokinase genes in pancreatic beta cells.
AB  - Insulin signaling is mediated by a complex network of diverging and converging
      pathways, with alternative proteins and isoforms at almost every step in the
      process. We show here that insulin activates the transcription of its own gene
      and that of the beta cell glucokinase gene (betaGK) by different mechanisms.
      Whereas insulin gene transcription is promoted by signaling through insulin
      receptor A type (Ex11-), PI3K class Ia, and p70s6k, insulin stimulates the betaGK
      gene by signaling via insulin receptor B type (Ex11+), PI3K class II-like
      activity, and PKB (c-Akt). Our data provide evidence for selectivity in insulin
      action via the two isoforms of the insulin receptor, the molecular basis being
      preferential signaling through different PI3K and protein kinases.

PMID- 11463382
TI  - SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive
      amplification.
AB  - Adaptive point mutation and amplification are induced responses to environmental
      stress, promoting genetic changes that can enhance survival. A specialized
      adaptive mutation mechanism has been documented in one Escherichia coli assay,
      but its enzymatic basis remained unclear. We report that the SOS-inducible, error
      prone DNA polymerase (pol) IV, encoded by dinB, is required for adaptive point
      mutation in the E. coli lac operon. A nonpolar dinB mutation reduces adaptive
      mutation frequencies by 85% but does not affect adaptive amplification, growth
      dependent mutation, or survival after oxidative or UV damage. We show that pol
      IV, together with the major replicase, pol III, can account for all adaptive
      point mutations at lac. The results identify a role for pol IV in inducible
      genetic change.

PMID- 11463383
TI  - Poliovirus RNA replication requires genome circularization through a protein
      protein bridge.
AB  - The mechanisms and factors involved in the replication of positive stranded RNA
      viruses are still unclear. Using poliovirus as a model, we show that a long-range
      interaction between ribonucleoprotein (RNP) complexes formed at the ends of the
      viral genome is necessary for RNA replication. Initiation of negative strand RNA
      synthesis requires a 3' poly(A) tail. Strikingly, it also requires a cloverleaf
      like RNA structure located at the other end of the genome. An RNP complex formed
      around the 5' cloverleaf RNA structure interacts with the poly(A) binding protein
      bound to the 3' poly(A) tail, thus linking the ends of the viral RNA and
      effectively circularizing it. Formation of this circular RNP complex is required
      for initiation of negative strand RNA synthesis. RNA circularization may be a
      general replication mechanism for positive stranded RNA viruses.

PMID- 11463384
TI  - Molecular organization of a recombinant subviral particle from tick-borne
      encephalitis virus.
AB  - The tick-borne encephalitis (TBE) flavivirus contains two transmembrane proteins,
      E and M. Coexpression of E and the M precursor (prM) leads to secretion of
      recombinant subviral particles (RSPs). In the most common form of these RSPs,
      analyzed at a 19 A resolution by cryo-electron microscopy (cryo-EM), 60 copies of
      E pack as dimers in a T = 1 icosahedral surface lattice (outer diameter, 315 A).
      Fitting the high-resolution structure of a soluble E fragment into the RSP
      density defines interaction sites between E dimers, positions M relative to E,
      and allows assignment of transmembrane regions of E and M. Lateral interactions
      among the glycoproteins stabilize this capsidless particle; similar interactions
      probably contribute to assembly of virions. The structure suggests a picture for
      trimer association under fusion-inducing conditions.

PMID- 11463385
TI  - Structural model for the cooperative assembly of HIV-1 Rev multimers on the RRE
      as deduced from analysis of assembly-defective mutants.
AB  - The functional efficacy of the HIV-1 Rev protein is highly dependent on its
      ability to assemble onto its HIV-1 RNA target (the RRE) as a multimeric complex.
      To elucidate the mechanism of multimeric assembly, we have devised two rapid and
      broadly applicable strategies for examining cooperative interactions between
      proteins bound to RNA, one based on cooperative translational repression of a two
      site reporter and the other on gel shift analysis with crude E. coli extracts.
      Using these strategies, we have identified two distinct surfaces of Rev (head and
      tail) that are critical for different steps in multimeric assembly. Our data
      indicate that Rev assembles cooperatively on the RRE via a series of symmetrical
      tail-to-tail and head-to-head protein-protein interactions. The insights into
      molecular architecture suggested by these findings have enabled us to derive a
      structural model for Rev and its multimerization on the RRE.

PMID- 11463386
TI  - Phosphoprotein-protein interactions revealed by the crystal structure of kinase
      associated phosphatase in complex with phosphoCDK2.
AB  - The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr
      160) of the CDK2 activation segment, the site of regulatory phosphorylation that
      is essential for kinase activity. Here we describe the crystal structure of KAP
      in association with pThr-160-CDK2, representing an example of a protein
      phosphatase in complex with its intact protein substrate. The major protein
      interface between the two molecules is formed by the C-terminal lobe of CDK2 and
      the C-terminal helix of KAP, regions remote from the kinase-activation segment
      and the KAP catalytic site. The kinase-activation segment interacts with the
      catalytic site of KAP almost entirely via the phosphate group of pThr-160. This
      interaction requires that the activation segment is unfolded and drawn away from
      the kinase molecule, inducing a conformation of CDK2 similar to the activated
      state observed in the CDK2/cyclin A complex.

PMID- 11463387
TI  - ATP-dependent proteases degrade their substrates by processively unraveling them
      from the degradation signal.
AB  - Protein unfolding is a key step in several cellular processes, including protein
      translocation across some membranes and protein degradation by ATP-dependent
      proteases. ClpAP protease and the proteasome can actively unfold proteins in a
      process that hydrolyzes ATP. Here we show that these proteases seem to catalyze
      unfolding by processively unraveling their substrates from the attachment point
      of the degradation signal. As a consequence, the ability of a protein to be
      degraded depends on its structure as well as its stability. In multidomain
      proteins, independently stable domains are unfolded sequentially. We show that
      these results can explain the limited degradation by the proteasome that occurs
      in the processing of the precursor of the transcription factor NF-kappaB.

PMID- 11463388
TI  - A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK
      inhibitor p27Kip1.
AB  - The Cks/Suc1 proteins associate with CDK/cyclin complexes, but their precise
      function(s) is not well defined. Here we demonstrate that Cks1 directs the
      ubiquitin-mediated proteolysis of the CDK-bound substrate p27Kip1 by the protein
      ubiquitin ligase (E3) SCF(Skp2). Cks1 associates with the F box protein Skp2 and
      is essential for recognition of the p27Kip1 substrate for ubiquitination in vivo
      and in vitro. Using purified recombinant proteins, we reconstituted p27Kip1
      ubiquitination activity and show that it is dependent on Cks1. CKS1-/- mice are
      abnormally small, and cells derived from them proliferate poorly, particularly
      under limiting mitogen conditions, possibly due to elevated levels of p27Kip1.

PMID- 11463389
TI  - RGS proteins provide biochemical control of agonist-evoked [Ca2+]i oscillations.
AB  - Agonist-evoked [Ca2+]i oscillations have been considered a biophysical phenomenon
      reflecting the regulation of the IP3 receptor by [Ca2+]i. Here we show that
      [Ca2+]i oscillations are a biochemical phenomenon emanating from regulation of
      Ca2+ signaling by the regulators of G protein signaling (RGS) proteins. [Ca2+]i
      oscillations evoked by G protein-coupled receptors require the action of RGS
      proteins. Inhibition of endogenous RGS protein action disrupted agonist-evoked
      [Ca2+]i oscillations by a stepwise conversion to a sustained response. Based on
      these findings and the effect of mutant RGS proteins and anti-RGS protein
      antibodies on Ca2+ signaling, we propose that RGS proteins within the G protein
      coupled receptor complexes provide a biochemical control of [Ca2+]i oscillations.

PMID- 11463390
TI  - Interleukin 2 receptors and detergent-resistant membrane domains define a
      clathrin-independent endocytic pathway.
AB  - Clathrin-dependent endocytosis has long been presented as the only efficient
      mechanism by which transmembrane receptors are internalized. We selectively
      blocked this process using dominant-negative mutants of Eps15 and showed that
      clathrin-mediated endocytosis of transferrin was inhibited, while endocytosis of
      interleukin 2 (IL2) receptors proceeded normally. Ultrastructural and biochemical
      experiments showed that clathrin-independent endocytosis of IL2 receptors exists
      constitutively in lymphocytes and is coupled to their association with detergent
      resistant membrane domains. Finally, clathrin-independent endocytosis requires
      dynamin and is specifically regulated by Rho family GTPases. These results define
      novel properties of receptor-mediated endocytosis and establish that the IL2
      receptor is efficiently internalized through this clathrin-independent pathway.

PMID- 11463391
TI  - PUMA induces the rapid apoptosis of colorectal cancer cells.
AB  - Through global profiling of genes that were expressed soon after p53 expression,
      we identified a novel gene termed PUMA (p53 upregulated modulator of apoptosis).
      The protein encoded by PUMA was found to be exclusively mitochondrial and to bind
      to Bcl-2 and Bcl-X(L) through a BH3 domain. Exogenous expression of PUMA resulted
      in an extremely rapid and profound apoptosis that occurred much earlier than that
      resulting from exogenous expression of p53. Based on its unique expression
      patterns, p53 dependence, and biochemical properties, PUMA may be a direct
      mediator of p53-associated apoptosis.

PMID- 11463392
TI  - PUMA, a novel proapoptotic gene, is induced by p53.
AB  - The p53 tumor-suppressor protein functions as a transcriptional activator, and
      several p53-inducible genes that play a role in the induction of apoptosis in
      response to p53 have been described. We have identified a novel gene named PUMA
      (p53 upregulated modulator of apoptosis) as a target for activation by p53. This
      gene encodes two BH3 domain-containing proteins (PUMA-alpha and PUMA-beta) that
      are induced in cells following p53 activation. PUMA-alpha and PUMA-beta show
      similar activities; they bind to Bcl-2, localize to the mitochondria to induce
      cytochrome c release, and activate the rapid induction of programmed cell death.
      Antisense inhibition of PUMA expression reduced the apoptotic response to p53,
      and PUMA is likely to play a role in mediating p53-induced cell death through the
      cytochrome c/Apaf-1-dependent pathway.

PMID- 11463393
TI  - Laboratory evaluation of the entomopathogenic fungus, Metarhizium anisopliae for
      the control of the groundnut bruchid, Caryedon serratus on groundnut.
AB  - The pathogenicity of five isolates of Metarhizium anisopliae to adult Caryedon
      serratus was evaluated in the laboratory. All the isolates tested were virulent
      to the beetle but pathogenicity varied among the isolates. One isolate, CPD 4 was
      consistently superior to all other isolates in terms of mortality of the beetle,
      protection of groundnut pods from damage, reduction in progeny production and
      repellency to the beetle. At 10 days post-treatment, adult mortality treated with
      0.1, 0.5 and 1.0g of dry conidia equivalent to 3.6x10(8), 1.8x10(9) and 3.6x10(9)
      conidia of isolate CPD 4 per 50g of groundnut pods was 100% which did not differ
      significantly from pirimiphos-methyl-treated pods at 10ppm. At the lowest dosage
      of 0.1g of conidia per 50g of pods, damage in pods protected with isolate CPD 4
      was 5% which did not differ significantly from the 2% damage in pods protected by
      pirimiphos-methyl at 10ppm but significantly differed from damage in untreated
      pods which was 26%. Isolate CPD 4 caused complete reduction in progeny emergence
      at all dosages tested. It also exhibited some degree of repellency to the beetle
      with percentage repellency values of between 40-79% at concentrations of 0.1-1.0g
      of conidia per 50g of groundnut pods. These combined virulence and repellency
      characteristics of this isolate may increase its protectant potential against C.
      serratus.

PMID- 11463394
TI  - An improved method for mass rearing of three liposcelid psocids (Psocoptera:
      Liposcelidae) infesting stored commodities.
AB  - An improved method of mass culturing liposcelid psocids is described that enables
      the production of large numbers of insects with minimal equipment and handling.
      The key factor was the provision of refuge by the addition of black chart papers
      (five pieces, each 10x2cm) inside the culture jars. A culture medium comprising
      whole wheat (14% moisture content), kibbled wheat, wholemeal wheat flour and
      brewer's yeast in the proportion of 10:10:10:0.1 (v/v) was tested on Liposcelis
      bostrychophila, L. entomophila and L. paeta. When reared on this medium with
      initial colonies of 10 adults, there was a 12-fold increase in L. bostrychophila,
      5-fold increase in L. entomophila and an 8-fold increase in L. paeta populations
      over a 4-week period. The method enables quick and simple extraction and handling
      of insects. This rearing method produced significantly (P<0.05) larger population
      numbers when compared with a range of published and unpublished methods.

PMID- 11463395
TI  - Intraspecific and interspecific competition in Callosobruchus maculatus (F.) and
      Callosobruchus subinnotatus (Pic) on stored bambara groundnut, Vigna subterranea
      (L.) Verdcourt.
AB  - Intraspecific competition was studied in Callosobruchus maculatus and
      Callosobruchus subinnotatus. Interspecific competition between the two bruchids
      was also studied to determine which of these species is likely to cause more
      damage to stored bambara groundnuts, Vigna subterranea in cases of joint
      infestation. Results showed that increasing the adult density up to 8 females per
      10g of bambara groundnut seeds did not significantly reduce the mean number of
      eggs laid per female, the number of eggs developing to the adult stage, or the
      weight of emerged adults of either species. The developmental period of the two
      species was also not significantly affected. The adult emergence curve of C.
      maculatus was similar to that of C. subinnotatus and was of the scramble type. C.
      maculatus performed better than C. subinnotatus in interspecific competition and
      it achieved this through a higher egg-laying ability and a higher rate of progeny
      production coupled with a shorter life-cycle. The implications of these findings
      with respect to damage and possible loss of stored bambara groundnut are
      discussed.

PMID- 11463396
TI  - Efficacy of essential oil of Ocimum basilicum L. and O. gratissimum L. applied as
      an insecticidal fumigant and powder to control Callosobruchus maculatus (Fab.)
AB  - Essential oils from sweet basil, Ocimum basilicum, and African basil, O.
      gratissimum, (Labiatae) grown in Guinea were obtained by steam distillation.
      Following exposure of newly emerged adult beetles (Callosobruchus maculatus) to
      12h of fumigation using pure essential oils at a dose of 25&mgr;l/vial, 80%
      mortality was recorded for O. basilicum, 70% for O. gratissimum and 0% in the
      control. A significant difference was observed between the responses of males and
      females with males exhibiting greater sensitivity. When 1g of aromatized powder
      was applied to adults, a 50% lethal concentration at 48h was found to be
      65&mgr;l/g for O. basilicum and 116&mgr;l/g of O. gratissimum oils. The essential
      oils from the two plant species exhibited a significant effect both on the egg
      hatch rate and on the emergence of adults. The egg hatch rate was reduced to 3%
      with O. basilicum and 15% with O. gratissimum using an essential oil
      concentration of 30&mgr;l, whereas the egg hatch rate for the control was 95%.
      When compared with the control (97%), adult emergence dropped to 0% with O.
      basilicum and to 4% with O. gratissimum. Storage bioassays were run to assess the
      long-term effect of powders aromatized with essential oils of Ocimum. Complete
      protection was observed over 3 months starting at a dose of 400&mgr;l in the case
      of both oils. From a germination test, it was concluded that aromatized powders
      have no significant effect on the seed germination rate. After 5d, a rate of 88%
      germination was seen in seeds treated with aromatized powder and protected from
      insects, compared with 97% for untreated seeds that were not exposed to insects.

PMID- 11463397
TI  - Performance of phosphine in fumigation of bagged paddy rice in indoor and outdoor
      stores.
AB  - Phosphine fumigation trials were carried out on bag-stacks of paddy rice to study
      the differences in gas loss rates and concentration-time (Ct) products achieved
      during the treatment of indoor and outdoor stacks. Stacks (89-132t) were
      fumigated singly under 250&mgr;m thick polyethylene sheeting, which was sealed
      with a double layer of sand-snakes to the concrete floor. Phosphine was applied
      as an aluminium phosphide formulation and the fumigations continued for 7 days.
      In the first experiment, stacks of paddy rice with moisture contents ranging from
      12.2 to 13.7% were held in either indoor or in outdoor storage and subjected to
      fumigation at the rate of 2, 3 or 4g of phosphine/tonne. The outdoor stacks held
      relatively low levels of phosphine with Ct products for the indoor stacks of 135,
      171 and 294gh/m(3), respectively, whilst the corresponding values for the outdoor
      stacks were 70, 85 and 166gh/m(3) only. The average gas loss rate was 14.5% per
      day for the indoor stacks and 29.5% for the outdoor stacks. In the second
      experiment, old stacks of paddy rice inside a godown, one each with grains at 8.8
      and 9.8% moisture content, were fumigated at 3g phosphine/tonne. Release of
      phosphine was delayed and fumigant sorption was less and therefore higher Ct
      products of 204 and 216gh/m(3) were achieved. In the stacks built outdoors, the
      resident infestations of Rhyzopertha dominica, Cryptolestes sp. and Oryzaephilus
      surinamensis were completely controlled despite lower Ct products. On the other
      hand, in the stacks of old paddy, R. dominica survived the treatment. Subsequent
      testing showed that the population had a degree of resistance to phosphine.

PMID- 11463398
TI  - Repellent effect of pea (Pisum sativum) fractions against stored-product insects.
AB  - Peas (Pisum sativum) are toxic to some stored-product insects. The repellent
      effect of fractions of pea seed to stored-product insects was evaluated in
      multiple-choice tests in which wheat kernels were dusted with fractions rich in
      either protein, fibre or starch at 0.001 to 10% (wt:wt). There was a negative
      correlation between pea protein concentration and the number of adults found in
      grain for Cryptolestes ferrugineus and Sitophilus oryzae, but not for Tribolium
      castaneum. Pea fibre repelled C. ferrugineus adults but not S. oryzae and T.
      castaneum. Pea starch did not repel any of the insects. One-week old and 6-week
      old C. ferrugineus were equally repelled by pea protein. Repellency was
      detectable 1h after exposure. Cryptolestes ferrugineus and S. oryzae did not
      become habituated to the repellent action of pea protein even after 4 weeks of
      exposure. Habituation was observed, however, when C. ferrugineus was exposed to
      pea fibre for 4 weeks. In a two-choice bioassay (0 vs. 0.1% and 0 vs. 1% pea
      protein), the pea-protein-treated grain had significantly fewer insects (C.
      ferrugineus, S. oryzae, Sitophilus zeamais, T. castaneum, and Tribolium confusum)
      than untreated grain. The properties of the pea protein fractions seem well
      suited for developing a natural stored grain protectant.

PMID- 11463399
TI  - Efficacy and fumigation characteristics of ozone in stored maize.
AB  - This study evaluated the efficacy of ozone as a fumigant to disinfest stored
      maize. Treatment of 8.9tonnes (350bu) of maize with 50ppm ozone for 3d resulted
      in 92-100% mortality of adult red flour beetle, Tribolium castaneum (Herbst),
      adult maize weevil, Sitophilus zeamais (Motsch.), and larval Indian meal moth,
      Plodia interpunctella (Hubner) and reduced by 63% the contamination level of the
      fungus Aspergillus parasiticus Speare on the kernel surface. Ozone fumigation of
      maize had two distinct phases. Phase 1 was characterized by rapid degradation of
      the ozone and slow movement through the grain. In Phase 2, the ozone flowed
      freely through the grain with little degradation and occurred once the molecular
      sites responsible for ozone degradation became saturated. The rate of saturation
      depended on the velocity of the ozone/air stream. The optimum apparent velocity
      for deep penetration of ozone into the grain mass was 0.03m/s, a velocity that is
      achievable in typical storage structures with current fans and motors. At this
      velocity 85% of the ozone penetrated 2.7m into the column of grain in 0.8d during
      Phase 1 and within 5d a stable degradation rate of 1ppm/0.3m was achieved.
      Optimum velocity for Phase 2 was 0.02m/s. At this velocity, 90% of the ozone dose
      penetrated 2.7m in less than 0.5d. These data demonstrate the potential
      usefulness of using ozone in managing stored maize and possibly other grains.

PMID- 11463400
TI  - Fumigation with carbonyl sulfide: a model for the interaction of concentration,
      time and temperature.
AB  - The new fumigant carbonyl sulfide offers an alternative to both methyl bromide
      and phosphine as a grain fumigant. Separate mathematical models for levels of
      kill, based on quantitative toxicological studies were developed for adults and
      eggs of the rice weevil Sitophilus oryzae (L.). These models suggest that
      fumigation exposure times for carbonyl sulfide will be a compromise between those
      of methyl bromide (typically 24h) and phosphine (7-10d) to achieve a very high
      kill of all developmental stages. S. oryzae eggs were more difficult to kill with
      carbonyl sulfide fumigation than the adults. At 30 degrees C, a 25gm(-3)
      fumigation killed 99.9% of adults in less than 1d, but took 4d to kill the same
      percentage of eggs. Models were generated to describe the mortality of adults at
      10, 15, 20, 25 and 30 degrees C. From these models it is predicted that
      fumigation with carbonyl sulfide for 1-2d at 30gm(-3) will kill 99.9% of adults.
      Furthermore the models illustrate that fumigations with concentrations below
      10gm(-3) are unlikely to kill all adult S. oryzae. Significant variation was
      observed in the response of eggs to the fumigant over the temperature range of 10
      to 30 degrees C. Models were generated to describe the mortality of eggs at 10,
      15, 20, 25 and 30 degrees C. As the temperature was reduced below 25 degrees C,
      the time taken to achieve an effective fumigation increased. Extrapolating from
      the models, a 25gm(-3) fumigation to control 99.9% of S. oryzae eggs will take
      95h (4d) at 30 degrees C, 77h (3.2d) at 25 degrees C, 120h (5d) at 20 degrees C,
      174h (7.5d) at 15 degrees C and about 290h (11d) at 10 degrees C. The role of
      temperature in the time taken to kill eggs with carbonyl sulfide cannot be
      ignored. In order to achieve the desired level of kill of all developmental
      stages, the fumigation rates need to be set according to the most difficult life
      stage to kill, in this instance, the egg stage.

PMID- 11463401
TI  - "Prediction of insect populations in grain storage". by Driscoll, R., Longstaff,
      B.C. and Beckett, S. Journal of Stored Products Research 36 (2000), 131-151.

PMID- 11463402
TI  - Keeping women in hospital and academic medicine.

PMID- 11463403
TI  - Rarity of adverse effects after 17D yellow-fever vaccination.

PMID- 11463404
TI  - Vasopressin or epinephrine: which initial vasopressor for cardiac arrests?

PMID- 11463405
TI  - Treatment of congenital hypothyroidism.

PMID- 11463406
TI  - Genotype-specific effects of smoking on risk of CHD.

PMID- 11463407
TI  - Repair of coarctation of the aorta and hypertension: does age matter?

PMID- 11463408
TI  - Age estimation of living people undergoing criminal proceedings.

PMID- 11463409
TI  - Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a
      report of two cases.
AB  - BACKGROUND: The yellow fever vaccine is regarded as one of the safest attenuated
      virus vaccines, with few side-effects or adverse events. We report the occurrence
      of two fatal cases of haemorrhagic fever associated with yellow fever 17DD
      substrain vaccine in Brazil. METHODS: We obtained epidemiological, serological,
      virological, pathological, immunocytochemical, and molecular biological data on
      the two cases to determine the cause of the illnesses. FINDINGS: The first case,
      in a 5-year-old white girl, was characterised by sudden onset of fever
      accompanied by headache, malaise, and vomiting 3 days after receiving yellow
      fever and measles-mumps-rubella vaccines. Afterwards she decompensated with
      icterus and haemorrhagic signs and died after a 5-day illness. The second patient
      a 22-year-old black woman-developed a sore throat and fever accompanied by
      headache, myalgia, nausea, and vomiting 4 days after yellow fever vaccination.
      She then developed icterus, renal failure, and haemorrhagic diathesis, and died
      after 6 days of illness. Yellow fever virus was recovered in suckling mice and
      C6/36 cells from blood in both cases, as well as from fragments of liver, spleen,
      skin, and heart from the first case and from these and other viscera fragments in
      case 2. RNA of yellow fever virus was identical to that previously described for
      17D genomic sequences. IgM ELISA tests for yellow fever virus were negative in
      case 1 and positive in case 2; similar tests for dengue, hantaviruses,
      arenaviruses, Leptospira, and hepatitis viruses A-D were negative. Tissue
      injuries from both patients were typical of wild-type yellow fever.
      INTERPRETATION: These serious and hitherto unknown complications of yellow fever
      vaccination are extremely rare, but the safety of yellow fever 17DD vaccine needs
      to be reviewed. Host factors, probably idiosyncratic reactions, might have had a
      substantial contributed to the unexpected outcome.

PMID- 11463410
TI  - Fever and multisystem organ failure associated with 17D-204 yellow fever
      vaccination: a report of four cases.
AB  - BACKGROUND: In 1998, the US Centers for Disease Control and Prevention was
      notified of three patients who developed severe illnesses days after yellow fever
      vaccination. A similar case occurred in 1996. All four patients were more than 63
      years old. METHODS: Vaccine strains of yellow fever virus, isolated from the
      plasma of two patients and the cerebrospinal fluid of one, were characterised by
      genomic sequencing. Clinical samples were subjected to neutralisation assays, and
      an immunohistochemical analysis was done on one sample of liver obtained at
      biopsy. FINDINGS: The clinical presentations were characterised by fever,
      myalgia, headache, and confusion, followed by severe multisystemic illnesses.
      Three patients died. Vaccine-related variants of yellow fever virus were found in
      plasma and cerebrospinal fluid of one vaccinee. The convalescent serum samples of
      two vaccinees showed antibody responses of at least 1:10240. Immunohistochemical
      assay of liver tissue showed yellow fever antigen in the Kuppfer cells of the
      liver sample. INTERPRETATION: The clinical features, their temporal association
      with vaccination, recovery of vaccine-related virus, antibody responses, and
      immunohistochemical assay collectively suggest a possible causal relation between
      the illnesses and yellow fever vaccination. Yellow fever remains an important
      cause of illness and death in South America and Africa; hence, vaccination should
      be maintained until the frequency of these events is quantified.

PMID- 11463411
TI  - Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised
      controlled trial.
AB  - BACKGROUND: Survival rates for cardiac arrest patients, both in and out of
      hospital, are poor. Results of a previous study suggest better outcomes for
      patients treated with vasopressin than for those given epinephrine, in the out-of
      hospital setting. Our aim was to compare the effectiveness and safety of these
      drugs for the treatment of in-patient cardiac arrest. METHODS: We did a triple
      blind randomised trial in the emergency departments, critical care units, and
      wards of three Canadian teaching hospitals. We assigned adults who had cardiac
      arrest and required drug therapy to receive one dose of vasopressin 40 U or
      epinephrine 1 mg intravenously, as the initial vasopressor. Patients who failed
      to respond to the study intervention were given epinephrine as a rescue
      medication. The primary outcomes were survival to hospital discharge, survival to
      1 h, and neurological function. Preplanned subgroup assessments included patients
      with myocardial ischaemia or infarction, initial cardiac rhythm, and age.
      FINDINGS: We assigned 104 patients to vasopressin and 96 to epinephrine. For
      patients receiving vasopressin or epinephrine survival did not differ for
      hospital discharge (12 [12%] vs 13 [14%], respectively; p50.67; 95% CI for
      absolute increase in survival 211.8% to 7.8%) or for 1 h survival (40 [39%] vs 34
      [35%]; p50.66; 210.9% to 17.0%); survivors had closely similar median mini-mental
      state examination scores (36 [range 19-38] vs 35 [20-40]; p50.75) and median
      cerebral performance category scores (1 vs 1). INTERPRETATION: We failed to
      detect any survival advantage for vasopressin over epinephrine. We cannot
      recommend the routine use of vasopressin for inhospital cardiac arrest patients,
      and disagree with American Heart Association guidelines, which recommend
      vasopressin as alternative therapy for cardiac arrest.

PMID- 11463412
TI  - Association between maternal serum concentration of the DDT metabolite DDE and
      preterm and small-for-gestational-age babies at birth.
AB  - BACKGROUND: DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) is highly
      effective against most malaria-transmitting mosquitoes and is being widely used
      in malaria-endemic areas. The metabolite, DDE (1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene), has been linked to preterm birth in small studies, but
      these findings are inconclusive. Our aim was to investigate the association
      between DDE exposure and preterm birth. METHODS: Our study was based on the US
      Collaborative Perinatal Project (CPP). From this study we selected a subset of
      more than 44000 eligible children born between 1959 and 1966 and measured the DDE
      concentration in their mothers' serum samples stored during pregnancy. Complete
      data were available for 2380 children, of whom 361 were born preterm and 221 were
      small-for-gestational age. FINDINGS: The median maternal DDE concentration was 25
      mg/L (range 3-178)-several fold higher than current US concentrations. The
      adjusted odds ratios (OR) of preterm birth increased steadily with increasing
      concentrations of serum DDE (ORs=1, 1.5, 1.6, 2.5, 3.1; trend p<0.0001). Adjusted
      odds of small-for-gestational-age also increased, but less consistently (ORs=1,
      1.9, 1.7, 1.6, 2.6; trend p=0.04). After excluding preterm births, the
      association of DDE with small-for-gestational-age remained. INTERPRETATION: The
      findings strongly suggest that DDT use increases preterm births, which is a major
      contributor to infant mortality. If this association is causal, it should be
      included in any assessment of the costs and benefits of vector control with DDT.

PMID- 11463413
TI  - Apolipoprotein E4 and coronary heart disease in middle-aged men who smoke: a
      prospective study.
AB  - BACKGROUND: The common isoforms of apolipoprotein E (apoE), E2, E3, and E4, are
      important determinants of plasma lipid concentrations, and the epsilon4 allele is
      associated with raised risk of coronary heart disease. We investigated whether
      the effect of smoking on coronary heart disease risk is affected by APOE
      genotype. METHODS: We enrolled 3052 middle-aged men who were free of coronary
      heart disease for prospective cardiovascular surveillance in the second Northwick
      Park Heart Study (NPHSII). Smoking habit was ascertained at baseline and yearly
      by questionnaire. APOE genotype was identified by PCR and restriction enzyme
      digestion. Endpoints were fatal coronary heart disease, non-fatal myocardial
      infarction, and coronary artery surgery and silent myocardial infarction at
      follow-up. FINDINGS: During 18836 person years of surveillance, 96 men had an
      acute myocardial infarction, 26 needed coronary artery surgery, and 14 had silent
      myocardial infarctions. Compared with never-smokers, risk of coronary heart
      disease in ex-smokers was 1.34 (95% CI 0.86-2.08) and in smokers it was 1.94
      (1.25-3.01). This risk was independent of other classic risk factors. In never
      smokers, risk was closely similar in men with different genotypes. Risk in men
      homozygous for the epsilon3 allele was 1.74 (1.10-2.77) in ex-smokers and 1.68
      (1.01-2.83) in smokers, whereas in men carrying the epsilon4 allele risk was 0.84
      (0.40-1.75) and 3.17 (1.82-5.50), respectively, with no significant differences
      in risk in the epsilon2 carriers. For the epsilon3 group, the genotype effect on
      risk was no longer significant after adjustment for classic risk factors
      (including plasma lipids). However, even after adjustment, smokers who were
      carriers of the epsilon4 allele, showed significantly raised risk of coronary
      heart disease compared with the non-smoking group (2.79, 1.59-4.91, epsilon4
      smoking interaction p=0.007). INTERPRETATION: Smoking increases the risk of
      coronary heart disease in men of all genotypes but particularly in men carrying
      the epsilon4 allele.

PMID- 11463414
TI  - Fits and strokes.

PMID- 11463415
TI  - Hepatitis and death following vaccination with 17D-204 yellow fever vaccine.
AB  - We describe a man vaccinated with the 17D204 strain of yellow fever virus, who
      subsequently died of yellow fever. Sequencing of the NS5-39 untranslated region
      showed that the virus isolated from the patient was identical to the vaccine
      strain of the same batch, and different from wild-type virus. Both viruses
      contained a mutation, although the association of this mutation with virulence is
      unknown. Severe, rapidly progressive, and ultimately fatal disease can follow use
      of the 17D204 vaccine strain. There is need for renewed discussion as to the
      safety of the vaccine and the indications for its use.

PMID- 11463416
TI  - Interferon-gamma microsatellite and rheumatoid arthritis.
AB  - Several non-HLA genes contribute to the susceptibility to rheumatoid arthritis
      (RA). A recent report noted an allele (126 bp [CA(13)]) of the interferon-gamma
      intron A microsatellite repeat strongly associated with both the occurrence and
      the severity of RA. We assessed this locus in an independent set of 128 controls
      and 93 prospectively recruited patients with early RA. The reported association
      could not be confirmed. This discrepancy might be due to technical problems,
      which could be avoided by the use of reference samples.

PMID- 11463417
TI  - Objective cosmetic and anatomical outcomes at adolescence of feminising surgery
      for ambiguous genitalia done in childhood.
AB  - There are few, if any data on the long-term outcome of feminising genital surgery
      for children with ambiguous genitalia. We present a retrospective study of
      cosmetic and anatomical outcomes in 44 adolescent patients who had ambiguous
      genitalia in childhood and underwent feminising genital surgery. Cosmetic result
      was judged as poor in 18 (41%) of these patients. 43 (98%) of 44 needed further
      treatment to the genitalia for cosmesis, tampon use, or intercourse. 23 (89%) of
      26 of genitoplasties planned as one-stage procedures required further major
      surgery. This information must be available to parents and clinicians planning
      such surgery. Cosmetic genital surgery in infancy needs to be reassessed in the
      light of these results.

PMID- 11463418
TI  - Cold feet and prolonged sleep-onset latency in vasospastic syndrome.
AB  - People with vasospastic syndrome have cold hands and feet and abnormal
      vasoconstriction after local cold exposure. Normally there is a circadian rhythm
      of distal vasodilation, with onset in the early evening, which directly
      influences ability to fall asleep. We gave a sleep questionnaire to 32 patients
      with primary vasospastic syndrome and 31 healthy controls. People with
      vasospasticity had significantly prolonged sleep-onset latency both at onset of
      night-time sleep and after nocturnal disturbance. This prolonged latency could be
      associated with impaired capacity for distal vasodilation.

PMID- 11463419
TI  - US experts urge referral for complex cancer surgeries.

PMID- 11463430
TI  - Kenya forms taskforce to tackle AIDS.

PMID- 11463434
TI  - Antibiotic resistance of bacteria in biofilms.
AB  - Bacteria that adhere to implanted medical devices or damaged tissue can encase
      themselves in a hydrated matrix of polysaccharide and protein, and form a slimy
      layer known as a biofilm. Antibiotic resistance of bacteria in the biofilm mode
      of growth contributes to the chronicity of infections such as those associated
      with implanted medical devices. The mechanisms of resistance in biofilms are
      different from the now familiar plasmids, transposons, and mutations that confer
      innate resistance to individual bacterial cells. In biofilms, resistance seems to
      depend on multicellular strategies. We summarise the features of biofilm
      infections, review emerging mechanisms of resistance, and discuss potential
      therapies.

PMID- 11463435
TI  - Medical use, misuse, and diversion of opioids in India.
AB  - In less-developed countries, opioids such as morphine are often not available for
      pain relief because of excessive regulations imposed to prevent their misuse and
      diversion. We describe the effect that these draconian measures have had on the
      availability of drugs for medical use in Kerala, India, and present results of a
      study, which we did to ascertain whether or not the misuse and diversion of
      opioids is as prevalent as the government reaction would suggest. We followed
      1723 patients in Calicut, India, who were being treated for pain with oral
      morphine on an outpatient home-care basis. Over 2 years, we did not identify any
      instances of misuse or diversion. These results suggest that, in the context of
      India as a less-developed country, oral morphine can be dispensed safely to
      patients for use at home. We recommend that palliative care programmes talk to
      concerned governmental authorities, to make them aware of the medical need for
      opioids, and communicate with local news media to increase awareness of
      palliative care and the use of these analgesics. Our project has overcome
      regulatory barriers that had interrupted availability of morphine and its use in
      pain relief in India.

PMID- 11463436
TI  - Human rights: a critical framework for the response to HIV/AIDS.

PMID- 11463437
TI  - HIV and human rights in refugee settings.

PMID- 11463438
TI  - Compulsory detention: limits of law.

PMID- 11463445
TI  - "SHOW ME". --Eliza Doolittle in My Fair Lady.

PMID- 11463446
TI  - Gain of chromosome 3 and loss of 13q are frequent alterations in pituitary
      adenomas.
AB  - Genetic changes underlying the tumorigenesis of pituitary adenomas (PA) are
      poorly characterized. To search for characteristic genomic imbalances involved in
      PA, we examined 38 cases: 12 hormone-secreting (HS) and 26 non-functioning (NF)
      PA, by comparative genomic hybridization. The most frequent DNA copy number
      change in both kinds of tumors was loss of 13q. Gains of chromosomes 3, 7 and 14,
      6p, and 20q were more frequent in HSPA than in NFPA. These data indicate that the
      13q region may harbor tumor suppressor genes determining the tumorigenesis of PA
      and gain in chromosome 3 may be related to hormone secretion. These findings
      provide a basis to search for candidate diagnostic markers of HSPA.

PMID- 11463447
TI  - Translocation (8;17;15;21)(q22;q23;q15;q22) in acute myeloid leukemia (M2). a
      four-way variant of t(8;21).
AB  - We report the results of cytogenetic, fluorescence in situ hybridization (FISH)
      and molecular analyses in a 15-year-old boy diagnosed with acute myeloid leukemia
      subtype M2 (AML-M2). Cytogenetic and FISH analyses, the latter with whole
      chromosome painting probes, revealed a complex translocation involving four
      chromosomes: t(8;17;15;21)(q22;q23;q15;q22). The observation of breakpoints at
      8q22 and 21q22 suggested a rearrangement of the ETO and AML1 genes, respectively.
      Using a dual-color FISH test with ETO and AML1 probes, we demonstrated an
      AML1/ETO fusion signal on the derivative chromosome 8. Reverse transcription
      polymerase chain reaction (RT-PCR) analysis showed the presence of AML1/ETO
      fusion transcripts identical to those found in classical t(8;21). The present
      case highlights the relevant role of the rearranged chromosome 8, which encodes
      the AML1/ETO fusion product in the pathogenesis of AML-M2.

PMID- 11463448
TI  - Near haploid childhood acute lymphoblastic leukemia masked by hyperdiploid line:
      detection by fluorescence in situ hybridization.
AB  - Near-haploid (<30 chromosomes) acute lymphoblastic leukemia (ALL) is a rare and
      unique subgroup of childhood common ALL associated with a very poor outcome. It
      may be underdiagnosed when masked by a co-existing hyperdiploid line, which has
      to be distinguished from the common good-prognostic hyperdiploid (>50
      chromosomes) ALL. We present three children in whom, by conventional
      cytogenetics, near-haploid ALL was detected on relapse. Using interphase FISH
      probes of chromosomes X, Y, 4, 12, and 21, we were able, in two cases, to trace
      the hidden near-haploid lines of approximately 5% and 20% of the cells, masked by
      hyperdiploid cells of approximately 80% and 70%, respectively; at relapse, the
      proportion was reversed, with predominant near-haploid lines of over 80% and
      residual hyperdiploidy of less than 10%. The near-haploid lines consisted of 24
      and 27 chromosomes, and always retained the second copy of chromosome 21 or its
      derivative, as detected in one of our patients by SKY. The hyperdiploid clones
      were the exact duplicates of the near-haploid ones and contained four and two
      copies of the chromosomes represented in two and one copies in the near-haploid
      stem line, respectively. Unlike the common hyperdiploid ALL, no trisomies were
      observed. The patients were all aged >10 years, with WBC 0.7-30 x 10(9)/L, and a
      common ALL phenotype. They were treated with the ALL-BFM-95 protocol, medium risk
      group, and responded well to 8 days of steroid therapy, but relapsed early,
      within 11 months, and died a few months later. Interphase FISH technique is
      recommended for the detection of cryptic near-haploid clones in the diagnostic
      survey of ALL. To assess the prognostic value of near-haploidy in the context of
      the ALL-BFM protocols, a larger cohort of patients is required.

PMID- 11463449
TI  - Subgroup of patients with Philadelphia-positive chronic myelogenous leukemia
      characterized by a deletion of 9q proximal to ABL gene: expression profiling,
      resistance to interferon therapy, and poor prognosis.
AB  - A major deletion of the region proximal to the rearranged ABL gene on 9q was
      found in 14/94 (15%) of chronic myelogenous leukemia Philadelphia-positive
      patients by interphase fluorescent in situ hybridization with the BCR/ABL extra
      signal dual-color probe. Preliminary results indicated that the prognosis of the
      deletion 9q patients is probably worse than that of the non-deletion 9q patients.
      Twelve of the 14 deletion 9q patients were treated with alpha-interferon and none
      had a major cytogenetic response. The median duration of the chronic phase in
      patients not undergoing BMT was significantly shorter for the deletion 9q
      patients as compared to the non-deletion 9q patients (p =.0144). DNA microarray
      technology was performed in order to compare the gene expression patterns between
      the two groups of patients. A number of genes exhibiting differential expression,
      especially involving cell adhesion and migration, were identified. This finding
      may identify a sub-group of CML patients with different cell properties and a
      relatively poor prognosis.

PMID- 11463450
TI  - Definition of chromosome aberrations in testicular germ cell tumor cell lines by
      24-color karyotyping and complementary molecular cytogenetic analyses.
AB  - Many of the reported karyotypes for adult testicular germ cell tumors (GCTs) are
      complex and incomplete, although the presence of an isochromosome 12p, i(12p),
      and gain of 12p material have consistently been found. Here, an accurate
      definition of the chromosome aberrations associated with four cell lines derived
      from GCTs (GCT27, H12.1, Tera1, and Tera2) has been produced using 24-color
      karyotyping by mulifluor in situ hybridization, comparative genomic hybridization
      analysis, and further fluorescence in situ hybridization analysis to confirm some
      chromosomal assignments and refine involvement of specific regions of 12p. There
      was karyotypic heterogeneity. Isochromosomes in addition to i(12p) were found, as
      were other rearrangements with breakpoints at or near centromeric regions. The
      most frequent non-centromeric breakpoints were at 1p31 approximately p32, 1p21
      approximately p22, 11q13, and Xq22, although consistent partner chromosomes were
      not involved. One cell line (Tera1) showed a subtle dosage increase in the copy
      number of a 12p probe known to be within the smallest overlapping region of
      amplification that has been defined in a number of testicular GCTs with amplicons
      at 12p11 approximately p12. The chromosome rearrangements and associated
      imbalances may be significant in GCT progression and the characterized cell lines
      can be used to investigate these further.

PMID- 11463451
TI  - Cytogenetic similarities between two types of salivary gland carcinomas: adenoid
      cystic carcinoma and polymorphous low-grade adenocarcinoma.
AB  - Adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA)
      are low-grade adenocarcinomas of salivary glands with a putative common
      histogenesis from the intercalated ducts but featuring distinct histological
      appearances. Hybrid tumors containing areas with histological patterns of both
      neoplasms have been reported but, to our knowledge, the question of their
      genotypic similarity has not yet been approached. As part of an ongoing study on
      cytogenetic characterization of salivary gland tumors, from a group of 24
      malignant neoplasms, three out of five cases of ACC and three of four cases of
      PLGA were selected for their similar karyotypic changes. All of them displayed
      chromosome 12 abnormalities, affecting the 12q12-q13 region in four (all ACC
      cases and one PLGA case), 12q22 in one PLGA case, and 12p12.3 in the remaining.
      From this group of neoplasms, one PLGA and one ACC showed the same
      t(6;12)(p21;q13). Our findings favor the concept that tumors of salivary glands
      displaying epithelial and myoepithelial phenotypes share a common histogenesis.

PMID- 11463452
TI  - Translocation (2;14) associated with complex rearrangements of the Ig heavy chain
      in non-Hodgkin lymphoma.
AB  - Cytogenetic analysis of a patient with non-Hodgkin lymphoma revealed the
      following karyotype: 49,XXX,t(2;14)(q21;q32),+4,+8,del(13)(q14q21). Southern blot
      analysis with an Ig region probe showed non-productive rearrangements indicative
      of a translocation involving the Ig locus. However, molecular cloning of the
      abnormal rearrangements did not show novel sequences derived from chromosome 2
      but showed that the BCL-6 gene was juxtaposed to the IgH enhancer. Three further
      clones with abnormal rearrangements involving the Ig locus, particularly
      Iggamma3, were isolated. This suggests that the mature lymphoid cells, in this
      patient, were capable of undergoing indiscriminate switch cleavage and
      religation.

PMID- 11463453
TI  - 6p abnormalities and TNF-alpha over-expression in retinoblastoma cell line.
AB  - Retinoblastoma is the most common primary intra-ocular tumor in childhood. It has
      been established that recurrent cytogenetic abnormalities are the hallmark of
      mostly all malignant tumors. Recurrent atypical cytogenetic abnormalities of the
      short arm of chromosome 6 were reported in several cases of retinoblastoma,
      mainly in association with reciprocal translocations. In the present study,
      alterations of chromosome 6 associated with retinoblastoma were studies in the Y
      79 and the WERI-Rb-1 cell lines established from highly malignant
      retinoblastomas. Fluorescence in situ hybridization (FISH) technique was used to
      identify the chromosomal breakpoint on 6p in this cell line. To perform this
      detection, yeast artificial chromosome (YAC) clones from p21 to p22 bands were
      used and the breakpoint was localized on 6p21.3. Previous studies had suggested
      that activation of some genes on 6p could be dependent on a translocation
      mechanism. Expression of a candidate gene localized near the chromosomal
      breakpoint was measured by immunocytochemistry and flow cytometry techniques. An
      enhancement of the tumor necrosis factor-alpha (TNF-alpha) protein expression in
      Y79 cells was detected by this approach. The relationship between TNF-alpha over
      expression and the malignancy of retinoblastoma is discussed.

PMID- 11463454
TI  - Pituitary tumorigenesis and hPit-1 cells.
AB  - Despite decades of clinical data verifying the success of therapeutic approaches
      to human pituitary tumors, a significant number of tumors progress and can be
      life-threatening. The development of better therapeutic strategies for pituitary
      tumors is complicated by the relative scarcity of human pituitary material for
      basic experimentation. Human pituitary tissue was used to derive cell cultures,
      and a cell line, hPIT-1. Molecular and functional analyses were used to further
      characterize the cells as human pituitary explants in vitro. Functional analyses
      of the cell cultures indicated that the cells were tumorigenic and of human
      folliculostellate origin. hPit-1 cells revealed numerous abnormalities of ploidy.
      Molecular analyses indicated the absence of expression of the following pituitary
      hormones or hormone subunits by this culture: growth hormone, prolactin, ACTH,
      FSHbeta, LHbeta, THbeta, and p-glycoprotein. By contrast, the cells expressed
      uniformly high levels of human follistatin mRNA. Finally, the cells are
      moderately tumorigenic in immune-deficient mice. Although the precise molecular
      genetic mechanisms for tumorigenesis in the established cell culture are unknown,
      the cells serve as a future resource in the study of pituitary tumor initiation,
      progression, and response to therapy.

PMID- 11463455
TI  - Comparative genomic hybridization in polycythemia vera and essential
      thrombocytosis patients.
AB  - Polycythemia vera (PV) and essential thrombocytosis (ET) are clonal chronic
      myeloproliferative disorders originating from a multipotent stem cell. Bone
      marrow examinations reveal chromosomal abnormalities in 15-43% of PV patients and
      5% of ET patients, but no specific recurring abnormality has been found to date.
      We aimed to find cytogenetic aberrations in PV and ET by comparative genomic
      hybridization (CGH), a relatively new molecular cytogenetic technique. In this
      study, CGH analysis was performed on peripheral blood leukocytes of 12 PV
      patients and 8 ET patients. One patient (8.3%) with PV had an abnormal karyotype
      with a deletion in 7q11.2 and one patient with ET (12.5%) had a gain in 18p.
      Peripheral blood analysis by CGH revealed a low frequency of cytogenetic
      abnormalities in PV and ET patients. However, using CGH we were able to detect
      two cytogenetic aberrations that were not reported previously in these disorders.

PMID- 11463456
TI  - Tetrasomy 21 as the sole acquired karyotypic abnormality in acute myeloblastic
      leukemia.
AB  - Peripheral blood and bone marrow analysis of a 79-year-old female led to a
      diagnosis of acute myeloblastic leukemia with differentiation (AML-M2).
      Chromosome analysis of the unstimulated bone marrow cells revealed 48,
      XX,+21,+21, and tetrasomy 21 was the sole cytogenetic abnormality in this
      constitutionally normal female patient.

PMID- 11463457
TI  - Allelic loss at 10q23.3 but lack of mutation of PTEN/MMAC1 in chromophobe renal
      cell carcinoma.
AB  - Chromophobe renal cell carcinoma (RCC) is characterized by loss of multiple
      chromosomes including chromosome 10. This study was undertaken to determine the
      LOH at the PTEN/MMAC1 locus (chromosome band 10q23.3) and to search for gene
      mutations in 15 chromophobe, 50 conventional, and 10 papillary RCCs as well as in
      10 renal oncocytomas. Loss of heterozygosity (LOH) wa seen at all informative
      loci in all chromophobe RCCs and in two conventional RCCs. We did not find
      mutations by analyzing exon 1 to 9 of the PTEN/MMAC1 gene using the PCR-SSCP
      technique in tumors with LOH at 10q23.3.

PMID- 11463458
TI  - Chromosomal gains and losses are uncommon in hairy cell leukemia: a study based
      on comparative genomic hybridization and interphase fluorescence in situ
      hybridization.
AB  - In contrast to other subtypes of lymphoproliferative malignancies, the genetic
      mechanisms underlying the pathogenesis of hairy cell leukemia (HCL) are unknown.
      We studied densely infiltrated splenic tissue of 14 cases of HCL for the presence
      of chromosomal gains and losses by comparative genomic hybridization (CGH).
      Chromosomal imbalances were detected in only four of the 14 cases. Chromosomal
      gains involved the regions 5q13-q31 (two cases) and 1p32-p36.2 (one case). A loss
      of the region 11q14-q22 was found in one additional patient. The imbalances
      affecting the regions 5q and 11q were confirmed by interphase fluorescence in
      situ hybridization (FISH) using PAC clone 144G9 (5q31) and YAC clones 755B11
      (11q22.3-q23.1) and 801E11 (11q22.3-q23.1 spanning the ATM gene) and occurred in
      61% to 75% of analyzed nuclei. The latter DNA probes and probes hybridizing to
      chromosomal regions, which are frequently deleted in other subtypes of non
      Hodgkin lymphomas (NHL), namely 9p21/ P16(INK4A), 13q14/D13S25, and 17p13/P53
      were subsequently applied to all 14 cases of HCL, but no additional abnormalities
      were found. We conclude that overrepresentation of chromosome 5 represents a
      recurrent aberration in HCL and that the commonly overrepresented region resides
      in 5q13-q31. Chromosomal imbalances including deletions of the tumor suppressor
      gene loci 9p21/P16(INK4A), 13q14/D13S25, and 17p13/P53 rarely occur in HCL in
      contrast to some other subtypes of B-cell NHL. The pathogenetic role of 11q/ATM
      alterations in HCL remains to be determined.

PMID- 11463459
TI  - Trisomy 16 as the sole anomaly in hematological malignancies. Three new cases and
      a short review.
AB  - We report on three cases, two with myelodysplastic syndrome (MDS) and one with
      acute lymphoblastic leukemia (ALL), displaying trisomy 16 as the sole cytogenetic
      anomaly. In none of these cases was a concomitant inv(16)(p13q22) detected by
      fluorescence in situ hybridization (FISH) or reverse transcription polymerase
      chain reaction (RT-PCR). Summarizing the literature, only six other cases
      cytogenetically characterized by an isolated trisomy 16 have been reported in
      hematological malignancies. These patients had either MDS, acute myeloblastic
      leukemia (AML), myelofibrosis, or ALL. All but one of these cases were aged less
      than 50.

PMID- 11463460
TI  - Substrate specificity of recombinant cysteine proteinase, CPB, of Leishmania
      mexicana.
AB  - The primary S(1) subsite specificity of a recombinant cysteine proteinase, CPB2.8
      Delta CTE, of Leishmania mexicana was investigated in a systematic way using a
      series of peptides derived from Abz-KLRFSKQ-EDDnp in which Arg was substituted by
      all natural amino acids (where Abz is ortho-amino-benzoyl and EDDnp is N-[2,4
      dinitrophenyl]-ethylenediamine). The peptides from this series with charged side
      chain amino acids, Cys, Cys(SBzl), and Thr(OBzl) were well hydrolysed. All other
      substitutions resulted in peptides that were resistant or hydrolysed very slowly
      and inhibited the enzyme with K(i) values in the range of 9--400 nM. Looking for
      natural substrates for CPB2.8, we observed that the recombinant enzyme failed to
      release kinin from human kininogen, an activity earlier observed with cruzipain
      from Trypanosoma cruzi (Del Nery et al., J. Biol. Chem. 272 (1997) 25713.). This
      lack of activity seems to be a result of the resistance to hydrolysis of the
      sequence at the N-terminal site of bradykinin in the human kininogen. The
      preferences for the S(3), S(2) and S(1)'-S(3)' for some amino acids were also
      examined using substrates derived from Abz-KLRFSKQ-EDDnp with variations at Lys,
      Leu, Phe, Ser and Lys, using the amino acids Ala, Phe, Leu, His or Pro. Peptides
      with Phe at P(1)' presented the highest affinity to the leishmanial enzyme. For
      comparison, some of the obtained peptides were also assayed with recombinant
      human cathepsin L and cruzain. The best substrates for CPB2.8 Delta CTE were also
      well hydrolysed by cathepsin L, however, the best inhibitors of the parasite
      enzyme have low affinity to cathepsin L. These promising data provide leads for
      the design of anti-parasitic drugs directed against the leishmanial enzyme.

PMID- 11463461
TI  - Adaptation of signature-tagged mutagenesis for Toxoplasma gondii: a negative
      screening strategy to isolate genes that are essential in restrictive growth
      conditions.
AB  - The obligate intracellular parasite Toxoplasma gondii can infect virtually any
      nucleated cell in any warm-blooded host. Through the effort of many researchers,
      we are beginning to learn what makes T. gondii such a successful protozoan
      parasite. A high throughput genetic screen that allows simultaneous examination
      of a large panel of mutants would greatly facilitate a global investigation of
      this parasite. Signature-tagged mutagenesis uses a unique DNA sequence to tag an
      individual mutant so that it can later be identified within a pool. This system
      allows the efficient identification of parasites carrying mutations in genes that
      are essential for growth in restrictive but not permissive conditions. We have
      generated a bank of approximately 4900 signature-tagged T. gondii tachyzoites
      represented in 89 pools, each of which contains 60 uniquely tagged mutant
      parasites. We have demonstrated the usefulness of this negative screening
      strategy with a tissue culture model for pyrimidine salvage using resistance to
      the pro-drug FUDR. Mutants that are defective for growth in any defined growth
      condition versus standard tissue culture conditions can now be identified (eg,
      sensitive to a specific drug, growth in a specialized cell line, or growth within
      animals).

PMID- 11463462
TI  - Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate
      gametogenesis of Plasmodium in the midgut of the mosquito.
AB  - Gametogenesis of Plasmodium in vitro can be induced by the combined stimulus of a
      5 degrees C fall in temperature and the presence of xanthurenic acid (XA). In
      vitro experiments showed that P. gallinaceum (EC(50)=80 nM) is much more
      sensitive to XA than P. berghei (9 microM), P. yoelii (8 microM), and P.
      falciparum (2 microM). However, in the mosquito vector, we do not know whether
      the temperature shift and XA are the only gametocyte-activating factors (GAF),
      nor do we know with certainty the true source(s) of XA in the mosquito blood
      meal. Previous studies indicate that XA is the only source of GAF in the
      mosquito. By defining, and then contrasting, the ability of an XA-deficient
      mutant of Aedes aegypti, with the wild-type mosquito to support exflagellation
      and ookinete formation in vivo, we determined the roles of parasite-, mosquito-
      and host blood-derived GAF in the regulation of gametogenesis of P. gallinaceum.
      Removal of both host and vector sources of GAF totally inhibited both
      exflagellation and ookinete production, whilst the lack of either single source
      resulted in only a partial reduction of exflagellation and ookinete formation in
      the mosquito gut. Both sources can be effectively replaced/substituted by
      synthetic XA. This suggests (1) both mosquito- and vertebrate-derived factors act
      as GAF in the mosquito gut in vivo; (2) the parasite itself is unable to produce
      any significant GAF activity. Studies are underway to determine whether
      vertebrate-derived GAF is XA. These data may form the basis of further studies of
      the development of new methods of interrupting malarial transmission.

PMID- 11463463
TI  - CAP5.5, a life-cycle-regulated, cytoskeleton-associated protein is a member of a
      novel family of calpain-related proteins in Trypanosoma brucei.
AB  - The cell shape of African trypanosomes is determined by the presence of an
      extensive subpellicular microtubule cytoskeleton. Other possible functions of the
      cytoskeleton, such as providing a potential framework for signalling proteins
      transducing information from the intracellular and extracellular environment,
      have not yet been investigated in trypanosomes. In this study, we have identified
      a novel cytoskeleton-associated protein in Trypanosoma brucei. CAP5.5 is the
      first member of a new family of proteins in trypanosomes, characterised by their
      similarity to the catalytic region of calpain-type proteases. CAP5.5 is only
      expressed in procyclic, but not in bloodstream, trypanosomes. Furthermore, CAP5.5
      has been shown to be both myristoylated and palmitoylated, suggesting a stable
      interaction with the cell membrane. A bioinformatics analysis of the trypanosome
      genome revealed a diverse family of calpain-related proteins with primary
      structures similar to CAP5.5, but of varying length. We suggest a nomenclature
      for this new family of proteins in T. brucei.

PMID- 11463464
TI  - The surface antigen SAG3 mediates the attachment of Toxoplasma gondii to cell
      surface proteoglycans.
AB  - The attachment of Toxoplasma gondii to target cells is mediated by recognition of
      cellular heparan sulfate proteoglycans (HSPGs). The present study was performed
      to determine whether SAG1 and SAG3, two of the parasite surface antigens anchored
      to the membrane via glycosylphosphatidylinositol groups (GPIs), are involved in
      the tachyzoite binding to proteoglycans. The use of recombinant soluble forms of
      these proteins allowed us to demonstrate that SAG3, but not SAG1, interacts
      specifically with cellular HSPGs. Indeed, soluble recombinant SAG3 protein
      (recSAG3) was found to bind to immobilized heparin, whereas recSAG1 did not
      interact with this glycoaminoglycan. The specific adherence of recSAG3 to CHO
      cells was inhibited by soluble glycoconjugates, of which heparin, fucoidan and
      dextran sulfate were the most effective. Moreover, binding of recSAG3 to two
      HSPGs-deficient cell mutants was reduced by up to 80%. Proteoglycan sulfation was
      critical for SAG3 adherence to HSPGs as incubation of cells in the presence of
      sodium chlorate drastically reduced the recSAG3 binding. Finally, preincubation
      of CHO cells with recSAG3 blocked the adsorption of radiolabelled Toxoplasma
      tachyzoites. Taken together, these results indicate that SAG3 is a first
      glycoaminoglycan-binding protein associated with Toxoplasma, and SAG3-HSPGs
      interactions are involved in the parasite attachment to target cells.

PMID- 11463465
TI  - Characterization of a retrotransposon-like element from Entamoeba histolytica.
AB  - The protozoan parasite Entamoeba histolytica is the causative agent of
      amoebiasis. The genome organization of this organism is not well understood. We
      had earlier reported the presence of a multicopy sequence, HMc, in E.
      histolytica. Subsequent analysis showed that HMc is a member of a retrotransposon
      family that we have named the E. histolytica retrotransposon-like element
      (EhRLE). Four other members of this family have been characterized. The EhRLE
      family is distributed across all chromosomes of the parasite. There are 140
      copies, which show minor sequence variation with respect to one another (2--4%
      from the consensus sequence). From a sequence analysis of five members of the
      EhRLE family, the complete EhRLE unit is estimated to be 4086 bp in length. It
      has a 27-mer inverted repeat at its ends. A pairwise comparison with sequences in
      the database showed a highly significant match of a part of EhRLE with reverse
      transcriptases (RT), especially those encoded by non-long terminal repeat
      retrotransposons. There are stop codons in all the five EhRLEs, but a continuous
      open reading frame of 464 amino acids could be reconstructed by comparing the
      sequences of several EhRLEs. The reconstructed sequence showed a much better
      identity with RT as compared with any of the original EhRLE sequences. The non
      pathogenic species, Entamoeba dispar, also contains this element, with 85%
      sequence identity with EhRLE. The data suggest that EhRLE may be a
      retrotransposon, but many of its members are probably nonfunctional due to the
      accumulation of mutations.

PMID- 11463466
TI  - An EBA175 homologue which is transcribed but not translated in erythrocytic
      stages of Plasmodium falciparum.
AB  - Plasmodia species can bind to the Duffy blood group antigen (Plasmodium vivax and
      P. knowlesi) or glycophorin A (P. falciparum) on human erythrocytes as receptors
      for the invasion of merozoites in the asexual life cycle. A number of proteins
      have been identified in P. vivax, P. knowlesi and P. falciparum that serve as
      parasite ligands for these interactions and this group of proteins form the
      erythrocyte binding protein (EBP) family. The availability of sequence data
      generated as part of the P. falciparum Genome Project has allowed the
      identification of other genes related to the known EBP family members. We
      describe the Psi EBA165 gene and show that it has four exons, a structure
      identical to that described for EBA175. Analysis using reverse transcriptase
      polymerase chain reaction (RT-PCR) has shown that all introns are spliced and
      that this gene is transcribed. The predicted protein would have the same
      structure as EBA175 containing the F1/F2 domains, a cysteine-rich region followed
      by a predicted transmembrane region and a short cytoplasmic tail, but the coding
      region of Psi EBA165 contains frameshifts. It was possible that the frameshifts
      may be corrected in the transcript, or alternatively, a mechanism could operate
      that allowed the translation machinery to read through the frameshifts.
      Antibodies that recognise EBA165 fusion proteins could not detect this protein in
      the P. falciparum parasites tested. Additionally, it was possible to disrupt the
      Psi EBA165 gene without affecting the parasite's ability to invade and grow in
      erythrocytes. These results suggest that the Psi EBA165 gene is a transcribed
      pseudogene.

PMID- 11463467
TI  - von Willebrand Factor A domain-related protein, a novel microneme protein of the
      malaria ookinete highly conserved throughout Plasmodium parasites.
AB  - The mosquito-invasive form of the malarial parasite, the ookinete, develops
      numerous secretory organelles, called micronemes, in the apical cytoplasm.
      Micronemal proteins are thought to be secreted during midgut invasion and to play
      a crucial role in attachment and motility of the ookinete. We found a novel
      ookinete micronemal protein of rodent malarial parasite Plasmodium berghei, named
      P. berghei von Willebrand factor A domain-related protein (PbWARP), and report it
      here as a putative soluble adhesive protein of the ookinete. The PbWARP gene
      contained a single open reading frame encoding a putative secretory protein of
      303 amino acids, with a von Willebrand factor type A module-like domain as a main
      component. Western blot analysis demonstrated that PbWARP was firstly produced 12
      h after fertilization by maturing ookinetes as SDS-resistant complexes.
      Recombinant PbWARP produced with a baculovirus system also formed SDS-resistant
      high-order oligomers. Immuno-electron microscopic studies showed that PbWARP was
      randomly distributed in the micronemes. PbWARP homologues also exist in human
      malarial parasites, Plasmodium falciparum and Plasmodium vivax. Highly conserved
      primary structures of PbWARP homologues among these phylogenetically distant
      Plasmodium species suggest their functional significance and the presence of a
      common invasion mechanism widely utilized throughout Plasmodium parasites.

PMID- 11463468
TI  - Molecular characterization of a 2-Cys peroxiredoxin from the human malaria
      parasite Plasmodium falciparum.
AB  - We have identified the 2-Cys peroxiredoxin (PfPrx-1) from the human malaria
      parasite Plasmodium falciparum. The PfPrx-1 showed the highest identity at amino
      acid level to the type II Prx among the currently known six subfamilies of
      mammalian Prx. The sequence identity between the PfPrx-1 and the previously
      reported 1-Cys Prx of P. falciparum (PfPrx-2), which corresponded to mammalian
      type VI Prx, was 25%. This suggests that the parasite possesses two Prx
      subfamilies. The PfPrx-1 showed significant sequence similarities with those of 2
      Cys peroxiredoxins of plants in the BLASTX search. This may reflect the
      consequences of a genetic transfer from an algal endosymbiont to the parasite
      nucleus during evolution. The recombinant PfPrx-1 protein (rPfPrx-1) was
      expressed as a histidine fusion protein in Escherichia coli and purified with Ni
      chromatography. The rPfPrx-1 existed as dimers under non-reducing conditions and
      dissociated into monomers in the presence of dithiothreitol. The PfPrx-1 protein
      also exists as a dimer in the parasites themselves. The reduction of the oxidized
      enzyme by the donation of electrons from E. coli thioredoxin (Trx)/Trx reductase
      system was demonstrated in its reaction with H(2)O(2), using the rPfPrx-1
      protein. These results suggested that the PfPrx-1 can act as a terminal
      peroxidase of the parasite Trx system. An elevated expression of the PfPrx-1
      protein seen in the trophozoite, the stage with active metabolism, suggests an
      association of the parasite Trx system with its intracellular redox control.

PMID- 11463469
TI  - Comparative analysis of Plasmodium reichenowi and P. falciparum erythrocyte
      binding proteins reveals selection to maintain polymorphism in the erythrocyte
      binding region of EBA-175.

PMID- 11463470
TI  - Negative selection of herpes simplex virus thymidine kinase in Toxoplasma gondii.

PMID- 11463471
TI  - Lymphotactin: a potential mediator of immunity against Theileria annulata
      infection of cattle.

PMID- 11463472
TI  - Recombinant falcipain-2 cleaves erythrocyte membrane ankyrin and protein 4.1.

PMID- 11463473
TI  - Stage-specific expression in Leishmania conferred by 3' untranslated regions of
      L. major leishmanolysin genes (GP63).

PMID- 11463474
TI  - Recombinational loss of a ribosomal DNA unit from the circular episome of
      Entamoeba histolytica HM-1:IMSS.

PMID- 11463475
TI  - Visualizing synapse formation and remodeling: recent advances in real-time
      imaging of CNS synapses.
AB  - The formation and maintenance of synaptic connections are critical in the
      development and plasticity of the central nervous system (CNS). Until recently,
      there have been few studies that followed the molecular sequences of the CNS
      synapse formation and maintenance. This situation changed dramatically after the
      introduction of green fluorescent protein (GFP)-based fluorescent probes and the
      development of lipophilic tracers of endocytotic membranes. These techniques
      enabled us to visualize presynaptic and postsynaptic structures in living neurons
      and illustrated active transport and remodeling of synaptic components.
      Furthermore, recent attempts to identify correlation between presynaptic and
      postsynaptic morphogenesis suggested very rapid time course of synapse formation
      at the individual axo-dendritic contact sites. These recent works clearly
      demonstrated the power of real-time imaging studies. Development of a wide
      variety of fluorescent probes and advances in the imaging techniques in future
      will further extend our knowledge on the molecular events that take place in the
      process of the development and maturation of synaptic junctions.

PMID- 11463476
TI  - Organization of the neurons of origin of the descending pathways from the ferret
      superior colliculus.
AB  - The superior colliculus (SC), through its descending projections to the brainstem
      and spinal cord, is involved in initiating sensory-driven orienting behaviors.
      Ferrets are carnivores that hunt both above and below ground using visual (and
      auditory) cues in the daylight but non-visual cues in darkness and in
      subterranean environments. The present investigation sought to determine whether
      the ferret SC shows organizational features similar to those found in other
      visually dominant animals (e.g. cats), or whether characteristics of colliculi
      from non-visually dominant animals (e.g. rodents) prevail. Injection of
      retrograde tracer into the identified targets of the colliculus (cervical spinal
      cord, the contralateral pontomedullary reticular formation, or the ipsilateral
      pontine reticular formation) labeled tectospinal, crossed tectoreticular, and
      ipsilateral tectoreticular neurons, respectively, within the adult ferret SC.
      Labeled tectospinal and crossed tectoreticular neurons were far outnumbered by
      neurons with ipsilateral reticular projections. Like those of their visually
      dominant relatives, ferret tectospinal neurons were well represented throughout
      the anterior-posterior extent of the SC and crossed tectoreticular neurons tended
      to be distributed more broadly across the intermediate gray layer than those of
      rodents. Thus, even though ferrets perform well as subterranean predators where
      non-visual cues initiate orienting behaviors, these anatomical characteristics
      indicate that their colliculi are organized similar to that of their visually
      dominant, carnivorous relatives.

PMID- 11463477
TI  - Protection of nigral neurons by GDNF-engineered marrow cell transplantation.
AB  - Marrow stromal cells, which have many characteristics of stem cells, populate
      various non-hematopoietic tissues including the brain. In the present study, the
      cDNA for the dopaminergic neurotrophic factor Glial Cell Line-Derived
      Neurotrophic Factor (GDNF) was delivered using marrow cells in the mouse 1-Methyl
      4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) model of Parkinson's disease.
      Following cross-sex intravenous bone marrow transplantation with male donor cells
      that had been transduced with GDNF (GDNF-BMT) or with non-manipulated marrow
      (Control-BMT), female recipient mice were subjected to systemic MPTP injections.
      Eight weeks after neurotoxin exposure, more tyrosine hydroxylase immunoreactive
      nigral neurons and striatal terminal density were observed in the GDNF-BMT mice
      compared with the Control-BMT group. In addition, following the expected initial
      behavioral hyperactivity in both groups, a significant difference in motor
      activity was detected between the two groups. GDNF immunoreactive male donor
      marrow derived cells were detected in the brains of GDNF-BMT mice but not in
      controls. These data indicate that marrow derived cells that seed the brain can
      express biologically active gene products and, therefore, can function as
      effective vehicles for therapeutic gene transfer to the brain.

PMID- 11463478
TI  - Long-term change in synaptic transmission in CA3 circuits followed by spontaneous
      rhythmic activity in rat hippocampal slices.
AB  - The relevance of long-term potentiation (LTP) at excitatory synapses in CA3
      circuits to generation of spontaneous epileptiform bursts in CA3 was investigated
      using rat hippocampal slices. CA3 pyramidal cells were antidromically stimulated
      through Schaffer collaterals. Evoked field potentials were extracellularly
      recorded from the stratum pyramidale and the stratum radiatum in CA3. Therefore,
      field potentials reflecting recurrent excitatory post-synaptic potentials (EPSPs)
      and inhibitory post-synaptic potentials (IPSPs) were positive at the stratum
      pyramidale and negative at the stratum radiatum. First, we tested how the
      amplitude of the evoked field potentials depends on a gamma-aminobutyric acid
      (GABA(A)) antagonist. Both of the positive and negative field potential peaks
      reduced in the medium containing penicillin (2 mM) or bicuculline (20 microM).
      This suggests that unmasked EPSPs due to suppression of IPSPs do not result in an
      increase in the evoked potentials. Second, CA3 pyramidal cells were
      antidromically stimulated by tetanic stimulation of Schaffer collaterals in order
      to induce LTP at synapses in CA3 circuits. Both of the positive and negative
      field potentials increased, suggesting that recurrent EPSPs were enhanced by
      tetanic stimulation. Induction of LTP at recurrent excitatory synapses was
      followed by spontaneous epileptiform bursts which persisted throughout
      experiments (approximately 1.5 h), while LTP of afferent synaptic potential
      evoked by hilar test stimulation was not induced. These results suggest that LTP
      at the afferent synapses is not necessary to spontaneous epileptiform bursts in
      CA3, but LTP at excitatory synapses between CA3 pyramidal cells contribute to
      spontaneous epileptiform bursts.

PMID- 11463479
TI  - Amplification of blood-brain barrier GLUT1 glucose transporter gene expression by
      brain-derived peptides.
AB  - Glucose is a critical nutrient for the brain, and the transport of this hexose
      from blood to brain is mediated by the blood-brain barrier (BBB) GLUT1 glucose
      transporter. The expression of the BBB-GLUT1 gene is compromised in different
      pathological conditions and it is modulated by brain trophic factors. The brain
      derived peptide preparation Cerebrolysin (Cl, EBEWE, Austria) increases the
      expression of the BBB-GLUT1 via mRNA stabilization. In order to gain more
      insights into the mechanism of BBB-GLUT1 gene regulation, the present
      investigation studied the effect of Cl on the expression of both the GLUT1
      protein and GLUT1 reporter genes in brain endothelial cultured cells (ECL). Cl
      markedly increased the expression of reporter genes containing GLUT1
      translational control elements and cis-acting elements involved in the
      stabilization of the GLUT1 mRNA transcript in a dose dependent manner. Cl
      produced only marginal effects on the reporter gene control lacking the GLUT1
      regulatory elements. In parallel experiments, Cl markedly increased the uptake of
      3H-2-deoxy-D-glucose and the levels of the GLUT1 protein measured by ELISA. Data
      presented here demonstrate: (i) that Cl increases the expression of BBB-GLUT1
      reporter genes containing regulatory cis-elements involved in the stabilization
      and translation of the GLUT1 transcript; (ii) that the effect on both regulatory
      elements cooperates to increase gene expression; and (iii) that the increased
      levels of the BBB-GLUT1 reporter genes in Cl-treated ECL cells are associated
      with an increase in the glucose uptake and in the expression of the GLUT1
      protein.

PMID- 11463480
TI  - Somatic noxious mechanical stimulation induces Fos expression in the postsynaptic
      dorsal column neurons in laminae III and IV of the rat spinal dorsal horn.
AB  - This study was conducted to ascertain the possible expression of Fos-like
      immunoreactivity (Fos-LI) in the postsynaptic dorsal column (PSDC) neurons in
      response to noxious mechanical stimulation of the forepaw glabrous area of normal
      rats. For this purpose, Fos immunohistochemistry along with Fluoro-Gold (FG)
      retrograde tracing was utilized. After repeated noxious pinching of the forepaw
      glabrous area, there was a marked increase in number of Fos-LI neurons in the
      dorsal horn, including Rexed's laminae III and IV, at C5-T1 spinal cord segments
      ipsilateral to the stimulation. Between segments C5 and T1, about 40% of the Fos
      LI neurons in laminae III and IV were distributed at segment C7. In the rats
      subjected to the noxious pinch coupled with FG injection into the right cuneate
      nucleus, PSDC neurons double labeled with Fos and FG were localized in the
      ipsilateral laminae III and IV extending from segment C5 to T1, with about 70% of
      them distributed at segments C6 and C7. At segment C6 or C7, double-labeled
      neurons made up about 10% of the PSDC neurons that projected their axons to the
      cuneate nucleus. Most of the double-labeled neurons appeared fusiform with their
      primary dendrites projected dorso-ventrally. The present results suggest that the
      morphologically distinct, subclasses of PSDC neurons in spinal laminae III and IV
      may contribute to the central transmission of mechanical nociceptive information
      through the dorsal column into the cuneate nucleus.

PMID- 11463481
TI  - Brain strategies for reading in the second language are determined by the first
      language.
AB  - Brain activation associated with reading was investigated in ten normal Japanese
      volunteers (five highly literate in both Japanese and English) and ten American
      native English speakers (five highly literate in both English and Japanese) in
      order to determine the neuroanatomic substrates employed in reading the first
      language (L1), and to determine the effect of L1 on the neurosubstrates involved
      in reading the second language (L2). The study was performed using blood
      oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging
      (fMRI) on a high-field (3.0T) system specifically optimized for fMRI. The
      activation patterns in Japanese subjects reading Japanese (L1) were substantially
      different from the patterns obtained in American subjects reading English text
      (L1). The activation patterns reading L2 were virtually identical to the patterns
      seen when reading L1 in both Japanese and English natives highly literate in both
      language systems. The results demonstrated that the neuroanatomical substrates
      underlying the cognitive processing of reading are differentially determined
      based on the language system. The study further indicates that the cognitive
      processes for reading in the second language involve the same cortical structures
      employed for the first language, supporting the hypothesis that the second
      language represents the cognitive extension of the first language.

PMID- 11463482
TI  - Changes in NADPH diaphorase expression in the fish visual system during optic
      nerve regeneration and retinal development.
AB  - The various functions of nitric oxide (NO) in the nervous system are not fully
      understood, including its role in neuronal regeneration. The goldfish can
      regenerate its optic nerve after transection, making it a useful model for
      studying central nervous regeneration in response to injury. Therefore, we have
      studied the pattern of NO expression in the retina and optic tectum after optic
      nerve transection, using NADPH diaphorase histochemistry. NO synthesis was
      transiently up-regulated in the ganglion cell bodies, peaking during the period
      when retinal axons reach the tectum, between 20-45 days after optic nerve
      transection. Enzyme activity in the tectum was transiently down-regulated and
      then returned to control levels at 60 days after optic nerve transection, during
      synaptic refinement. To compare NO expression in the developing and regenerating
      retina, we have looked at NO expression in the developing zebrafish retina. In
      the developing zebrafish retina the pattern of staining roughly followed the
      pattern of development with the inner plexiform layer and horizontal cells having
      the strongest pattern of staining. These results suggest that NO may be involved
      in the survival of ganglion cells in the regenerating retina, and that it plays a
      different role in the developing retina. In the tectum, NO may be involved in
      synaptic refinement.

PMID- 11463483
TI  - Effects of temporal gaps between successive fixation targets on discrimination
      performance and evoked brain activity.
AB  - Planning and executing of action in real-world conditions require continuous
      sensory input from many modalities. At the same time, sensory functions depend on
      reafferent and efference-copy information flow as imposed by motor actions. We
      studied how a specific oculomotor task influences afferent visual processing.
      Twenty healthy adults performed visually guided saccades. Between the offset of a
      fixation light and the onset of a new visual target a temporal gap of a duration
      of about 200 ms was introduced. This time structure is known from previous
      studies to elicit saccades at express latencies. In a control condition, 'no gap'
      was used. During eye movements one of four visual patterns with different
      orientations was presented, triggered by the horizontal electro-oculogram. We
      analyzed discrimination performance and the simultaneously recorded multichannel
      EEG activity. In the gap condition, shorter saccadic latencies were accompanied
      by significant more correct perceptual judgments. However, brain activity, as
      quantified by global field power, evoked component latency and topographical
      descriptors (centers of gravity or centroids) were not affected by the gap. This
      contrasts the notion that parieto-occipital areas are the most important sites of
      sensorimotor integration. Furthermore, the presence of a visual masking stimulus
      did not degrade discrimination performance, demonstrating that local retinal
      afterimages were not used for perceptual decisions. We conclude that intra
      saccadic visual processing is influenced by pre-saccadic events. Under the short
      time constraints prevalent in the saccadic task, fixation target cues are not
      only used for motor planning but also influence the visibility of visual patterns
      presented during the eye movement.

PMID- 11463484
TI  - Niflumic acid reduces the hyperpolarization-activated current (I(h)) in rod
      photoreceptor cells.
AB  - We examined the effects of niflumic acid (NFA), a chloride channel blocker, on
      the hyperpolarization-activated current (I(h)) in newt rod photoreceptors. At 100
      microM, NFA delayed the activation of I(h) induced by hyperpolarizing voltage
      pulses to -83 mV from a holding potential of -43 mV, and reduced the steady-state
      current. However, reduction by NFA was weakened when I(h) was activated by
      hyperpolarizing steps to -123 mV, suggesting that these effects were voltage
      dependent. The suppressive effects of NFA on I(h) were accompanied by a negative
      shift in activation voltage. NFA also delayed the relaxation of I(h) tail
      currents, showing that this drug also inhibited deactivation of the current. The
      reversal potential and the fully activated conductance were not affected. These
      observations suggest that NFA reduces I(h) by modifying the gating kinetics of
      the underlying channels. The suppressive actions of NFA remained when
      intracellular Ca2+ was strongly chelated, and the failure of suppression by NFA
      in inside-out patches suggests that the agent may act on the I(h) channel from
      the extracellular side. These results, obtained in rod photoreceptors, are
      consistent with similar effects of NFA on I(f) in cardiac myocytes, suggesting
      that both currents share similar pharmacological properties.

PMID- 11463487
TI  - Chemically induced rat mammary tumor treated with tamoxifen showed decreased
      expression of cyclin D1, cyclin E, and p21(Cip1).
AB  - We studied the effects of tamoxifen (TAM) on the growth of 7,12
      dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor and the expression of
      cyclin D1, cyclin E, p21(Cip1), and estrogen receptors (ER) by performing
      immunohistochemistry and Western blot analysis. When tumor size reached between
      10 and 15mm in the largest dimension, the rats were divided into a DMBA-control
      group and a DMBA-TAM group. The administration of TAM markedly decreased the
      tumor development and showed decreased expression of bromodeoxyuridine, cyclin
      D1, cyclin E, and p21(Cip1) when compared with those of the DMBA-control group;
      however, a few tumors showed progressive growth in spite of TAM treatment. These
      tumors had decreased expression of ER. This study suggests that TAM suppresses
      tumor development through the down-expression of cyclin D1 and cyclin E.

PMID- 11463488
TI  - Differential effects of acetaminophen pretreatment on hepatic aflatoxin B(1)-DNA
      binding, cellular proliferation, and aflatoxin B1-induced hepatic foci in rats
      and hamsters.
AB  - Effects of acetaminophen (AAP) pretreatment on hepatic aflatoxin B1 (AFB(1))-DNA
      binding, cellular proliferation, and AFB(1)-induced glutathione S-transferase
      placental form (GST-P) positive hepatocytes and foci have been examined in young
      male rats and hamsters. Intraperitoneal (i.p.) dosing of 600mg AAP 3h before
      AFB(1) i.p. injection showed three-fold more AFB(1)-DNA binding in hamsters and
      40% less binding in rats. Cell proliferation analyzed by bromodeoxyuridine
      incorporation was not significant (0.4-0.6%) 24-96h after AAP (600mg) treatment
      of rats; however, proliferation was stimulated and was maximum (11%) in hamsters
      at 72h after AAP treatment. Dosing of rats with AFB(1) alone at 0.5 or 2.5mg
      level gave an appreciable number of GST-P positive minifoci (two to nine cells)
      with a few foci larger than 100 microm; pretreatment with AAP (300 or 600mg) 48h
      before 0.5 or 2.5mg AFB(1) had no effect on the number and focal area of foci. In
      hamsters, 1 or 2mg AFB(1) alone yielded GST-P positive hepatocytes without any
      minifoci. Pretreatment with AAP (600mg) 48 or 72h before 1 or 2mg AFB(1) produced
      increases in both GST-P positive hepatocytes and minifoci. Thus, marked changes
      are observed after AAP pretreatment in hamsters compared to rats.

PMID- 11463489
TI  - Strain variation in renal carcinogenesis by N-ethyl-N-hydroxyethylnitrosamine in
      F1 (Wistar-Fischer) rats.
AB  - The present study was conducted to compare the incidences of renal tumors in
      Wistar (W), Fischer (F) and F1 rats (WF: female Wistar rats x male Fischer rats;
      FW: female Fischer rats x male Wistar rats) induced by N-ethyl-N
      hydroxyethylnitrosamine (EHEN). Levels of 8-OHdG in renal DNA were also
      investigated in Wistar and Fischer rats. After 2000 ppm of EHEN was administered
      orally for 2 weeks, the animals were fed basal diet until week 32. Wistar males
      and females demonstrated significantly higher sensitivity regarding induction of
      renal lesions, while both WF and FW rats had similar incidences, generally
      intermediate between those for the two parent strains. The formation of 8-OHdG
      was maximal 60-180 min after an intraperitoneal dose of 750 mg/kg to Wistar and
      Fischer rats, which correlates with the increase tending to the incidence of
      renal tumors in male and female Wistar and Fischer rats. The results suggest that
      EHEN induction of renal tumors is related to oxygen radical damage and that the
      genes in the Wistar strain responsible for the sensitivity are not inherited in a
      sex-dependent fashion, despite the male being more susceptible.

PMID- 11463490
TI  - Frequent loss of heterozygosity on multiple chromosomes in Chinese esophageal
      squamous cell carcinomas.
AB  - Analysis of the loss of heterozygosity (LOH) detected by polymerase chain
      reaction techniques using 18 polymorphic markers localized to chromosomes 3p, 5,
      17, and 18q in 40 Hong Kong Chinese esophageal squamous cell carcinoma (ESC)
      patients showed that multiple alterations on several chromosomes are involved in
      ESC development. The LOH rates detected for markers on chromosome 3 ranged from
      44.0 to 85.7%, for chromosome 5 from 40.9 to 61.9%, for chromosome 17 from 40.0
      to 100%, and for chromosome 18 from 38.9 to 58.3%. No significant association was
      observed between LOH and the clinical and histopathological parameters.

PMID- 11463491
TI  - Predicting chemotherapy response and comparing with P-glycoprotein expression
      using technetium-99m tetrofosmin scan in untreated malignant lymphomas.
AB  - The purposes of this study were to predict the chemotherapy response of untreated
      malignant lymphomas (ML) using a technetium-99m tetrofosmin (Tc-TF) scan and to
      compare Tc-TF results with P-glycoprotein (Pgp) expression. Before undergoing
      chemotherapy, 25 patients with ML were enrolled in this study. Tc-TF scan was
      performed 10 min after intravenous injection of Tc-TF. Immunohistochemical
      analyses were performed on multiple sections of ML specimens to evaluate Pgp
      expression. The chemotherapy response was evaluated in the first 1-2 years after
      the completion of treatment. The mean tumor-to-background ratio of the 15
      patients with good responses (3.23+/-0.56) was significantly higher than that of
      the ten patients with poor responses (1.18+/-0.11). All of the 15 patients with
      good responses had positive Tc-TF scan results, but negative Pgp expression.
      Among the ten patients with poor responses, all had negative Tc-TF scan results,
      but six had positive Pgp expression and four had negative Pgp expression.
      Significant differences in the incidences of good and poor responses were found
      between patients with positive Tc-TF scan results and patients with negative Tc
      TF scan results and between patients with positive Pgp expression and patients
      with negative Pgp expression. No significant differences in the incidences of
      good and poor responses were found between Hodgkin's disease patients and non
      Hodgkin's lymphoma patients, stage I-II patients and III-IV patients, patients
      aged >40 and patients aged < or =40 years, and patients with and without B
      symptoms. Compared with other prognostic factors, Tc-TF scan results and Pgp
      expression more accurately predict the chemotherapy response in patients with ML.

PMID- 11463492
TI  - Identification and characterization of human deoxyguanosine kinase cDNA
      fragments.
AB  - Mitochondria require deoxyribonucleoside triphosphates for the synthesis of their
      DNA and one of the enzymes responsible for the initial phosphorylation of purine
      deoxyribonucleoside is deoxyguanosine kinase (dGK; EC 2.7.1.113). Recent studies
      have suggested that dGK in addition to deoxycytidine kinase phosphorylates
      several anti-cancer agents, such as 9-beta-D-arabinofuranosylguanine (Ara-G),
      cladribine (CdA), and fludarabine. There appear to coexist several mRNA fragments
      of dGK. In the present study we found 10 fragments, the longest fragment had
      834bp, and represented the entire open reading frame of dGK (780bp). The nine
      additional fragments detected ranged from 807 to 269bp. All the fragments were
      found to contain the specific mitochondria translocation signal sequence.
      Expression of these fragments in Escherichia coli demonstrated that only the full
      length dGK resulted in a protein that could phosphorylate CdA and Ara-G. Given
      the difficulty to measure the full-length dGK, these data are of value for
      studying the mRNA gene expression of dGK in cell lines and in leukemic cells from
      patients.

PMID- 11463493
TI  - Mass spectrometric high-throughput analysis of serum-free conditioned medium from
      cancer cell lines.
AB  - Proteins secreted by cancer cells may be useful as tumor markers. We analyzed
      constituents produced by cells grown in serum-free conditioned medium to avoid
      confounding factors present in serum. Mass spectrometric techniques were used to
      obtain expression patterns of constituents between 2000 and 15000 Da from as
      little as 1 microl of crude sample. This protocol can produce distinctive mass
      profiles from 16 cell lines within 1 h. Thus, differential display by mass
      spectrometry will expedite the discovery of peptides specifically secreted by
      particular cells. These data illustrate the advantage of this strategy over the
      conventional approach of electrophoretic separation of serum samples.

PMID- 11463494
TI  - Different features of angiogenesis between ovarian and breast carcinoma.
AB  - Angiogenesis assessed by immunohistochemical staining for endothelial cells has
      been widely accepted as an independent prognostic factor in human breast
      carcinoma. However, the clinicopathologic significance of angiogenesis is still
      being argued in ovarian carcinoma. Therefore, we retrospectively analyzed the
      clinicopathologic significance of angiogenesis in ovarian carcinoma compared with
      that in breast carcinoma. After vessels were stained with CD34-monoclonal
      antibody, the areas with the highest number of intratumoral microvessels were
      assessed in a 200x field in 42 ovarian carcinoma and 41 breast carcinoma.
      Intratumoral microvessel density (IMD) in ovarian carcinoma was significantly
      lower than that in breast carcinoma. Further, the difference of IMD from tumor to
      tumor in ovarian carcinoma was smaller than that in breast carcinoma. IMD was
      correlated with tumor grade, but not with other clinicopathologic variables in
      ovarian carcinoma. Although the patients with high-IMD tumor revealed a poorer
      prognosis than those with low-IMD tumor in breast carcinoma, IMD had no
      influential effects on the survival of the patients with ovarian carcinoma. Our
      comparative analysis of IMD in ovarian carcinoma with that in breast carcinoma
      indicates that angiogenesis may play an important role in the transient of
      ovarian neoplasms, but not in the progression of ovarian carcinomas, and that the
      biological roles of angiogenesis might be different, depending on histologic
      subtype.

PMID- 11463495
TI  - Cholesterol catabolism in patients with acute myelogenous leukemia and
      hypocholesterolemia: suppressed levels of a circulating marker for bile acid
      synthesis.
AB  - Hypocholesterolemia is a frequent finding in patients with acute myelogenous
      leukemia (AML) and in other types of malignancies. Since bile acids are major
      excretion products of cholesterol, the hepatic degradation of cholesterol to bile
      acids was investigated in AML patients by analyzing a circulating marker for bile
      acid synthesis. In addition, plasma levels of a marker for cholesterol synthesis
      were determined. The plasma levels of 7alpha-hydroxy-4-cholesten-3-one,
      reflecting bile acid production, were markedly lower in patients with AML than in
      healthy controls. The median levels were 3.3 and 18.5ng/ml (P<0.0001) in the AML
      patients (n=29) and the healthy subjects (n=16), respectively. The plasma levels
      of 7-dehydrocholesterol, reflecting hepatic cholesterol synthesis, were similar
      for the AML patients and the controls. The results show that the conversion of
      cholesterol to bile acids was suppressed in AML patients, a phenomenon that may
      result in a decreased intestinal absorption of cholesterol and subsequent
      hypocholesterolemia.

PMID- 11463496
TI  - Acceleration of lung metastasis by up-regulation of CD44 expression in
      osteosarcoma-derived cell transplanted mice.
AB  - The effect of CD44-phenotypic expression on metastasis to the lung was studied
      using a spontaneous murine osteosarcoma-derived cell line, POS-1, stimulated with
      lipopolysaccharide (LPS). POS-1 cells were inoculated into the hind paws of 20
      C3H/HeJ mice and produced a visible mass in all mice in 5 weeks, and these
      transplanted tumors resulted in lung metastasis in all mice. The number of
      metastatic foci in the lungs was 12.0+/-2.1 (mean+/-SD) with LPS-stimulated
      cells, which was significantly higher than that of unstimulated cells (5.8+/-1.4;
      N=10 for each; P<0.05). Hyaluronate (HA), a ligand of CD44, inhibited a number of
      lung metastases in a dose-dependent manner (0.5% HA, 3.0+/-1.1; 0.005% HA, 5.1+/
      1.5; without HA, 8.6+/-1.7; N=10 for each; P<0.05, each group with HA versus the
      group without HA). Adhesion assay by coculturing POS-1 cells and lung
      microvascular endothelial cells on culture plate showed that the adhesion was
      significantly lower in HA treated POS-1 than those without HA (1.18+/-0.12 and
      2.74+/-0.17, respectively, P<0.05). These results suggest that lung metastasis
      was accelerated by up-regulation of CD44.

PMID- 11463497
TI  - Expression of p21(WAF1/CIP1) and p53 proteins in gastric carcinoma: its
      relationships with cell proliferation activity and prognosis.
AB  - The expressions of p21(WAF1/CIP1), p53 proteins, and Ki-67 antigen were
      investigated immunohistochemically in 190 primary gastric carcinomas. Of the 190
      tumors, 40.5% positively expressed p21(WAF1/CIP1) and 42.1% positively expressed
      p53. The expression of p21(WAF1/CIP1) was significantly associated with
      clinicopathological factors including gender, tumor size, status of lymph node,
      and clinicopathological stage (P<0.05 for all), but p21(WAF1/CIP1) expression
      showed no clear correlation with Ki-67 labeling index. The mean Ki-67 labeling
      index was significantly higher in p53-positive cases than p53-negative cases
      (P<0.0001). However, among the clinicopathological factors examined, expression
      of p53 correlated only with age. Univariate and multivariate survival analyses
      revealed that clinicopathological stage (P<0.001) and expression status of
      p21(WAF1/CIP1) (P<0.05) were independent prognostic factors. Neither the
      expression status of p53 nor the Ki-67 labeling index, however, influenced the
      prognosis of patients with gastric cancer.

PMID- 11463498
TI  - RET rearrangements in familial papillary thyroid carcinomas.
AB  - Familial papillary thyroid carcinoma (FPTC) is an inherited tumor characterized
      by a more aggressive phenotype than that of its sporadic counterpart. Its mode of
      inheritance as well as its genetic and molecular bases are still poorly
      understood. On the contrary, genetic alterations in sporadic papillary thyroid
      carcinoma (PTC) are better characterized, the most common one involving the
      activation of the proto-oncogene RET through somatic rearrangements. In the
      present study, we investigated by interphase fluorescence in situ hybridization
      the presence of RET rearrangements in a series of 20 FPTC. We show that one FPTC
      and the adenoma from the same patient carry a RET rearrangement (type PTC1) and
      that this rearrangement is absent in the germline. Furthermore, we excluded a RET
      haplotype sharing in two brothers of the same family. These results show that RET
      rearrangements can indeed be found in FPTC and confirm that RET is not involved
      in the inherited predisposition to FPTC.

PMID- 11463499
TI  - Low detection rate of p53 antibodies in sera of soft tissue sarcoma patients.
AB  - Accumulation of the p53 gene product can lead to its immunogenic appearance and
      the generation of p53 serum antibodies (p53ab). In different cancer types the
      occurrence of detectable p53ab has an independent prognostic impact. In spite of
      the known p53 protein overexpression rate in soft tissue sarcomas (STS), up to
      70%, there have been no investigations done on p53ab in serum in STS patients. In
      this prospective study of 50 STS patients, we investigated the presence of serum
      p53ab using an enzyme-linked immunosorbent assay system and the presence of p53
      overexpression in the appropriate tissue specimen immunohistochemically. Using
      Kruskal-Wallis chi(2) and Kaplan-Meier tests the results were then correlated to
      histopathological and clinical data. Six of the 50 patients (12%) showed p53ab
      detectable in the serum, and 56% (28/50) of the tumors were p53
      immunohistochemically positive. Four of the six p53ab positives (66%) had
      immunohistochemically p53 positive and two (33%) had negative tumors. Altogether
      four of the 50 patients (8%) were positive for p53ab in serum as well as for p53
      immunohistochemistry in tumor tissue specimens. Twenty patients (40%) were
      negative for both. All of the p53ab positive patients had stage I or II tumors.
      Excluding tumor stage there was no p53ab correlation to histopathological,
      clinical or prognostic parameters. We conclude that in STS patients, p53ab also
      occurs but in contrast to other tumor types at a relatively low frequency.
      According to our results, the clinical value of p53ab seems to be limited in STS
      patients.

PMID- 11463500
TI  - A basin-wide approach to dredged material management in New York/New Jersey
      Harbor.
AB  - In the last decade, an area of increasing estuarine research in the New York/New
      Jersey Harbor has been the identification of toxic contaminant sources, mapping
      of contaminant levels in water and sediments, and assessment of contaminant
      accumulation in biota. The accumulation of anthropogenic contamination in the
      harbor's sediments has occurred for centuries, primarily from land-based
      municipal and industrial sources. Contaminants from land-based sources introduced
      into surface waters rapidly become scavenged by suspended particles that then
      tend to settle to the bottom, primarily in deep areas, such as berths and
      navigation channels. Several million cubic meters of sediments must be dredged
      annually to clear navigation channels. In the past, the dredged material was
      disposed in a designated ocean site. However, in1992, new testing procedures were
      implemented, and much of the harbor's dredged material was determined to be
      unsuitable for ocean placement. It is ironic that these restrictions came at a
      time when the quality of harbor sediments is improving, largely because of
      pollution controls implemented as a result of the Clean Water Act and other
      environmental measures put in place by government and industry. For example, the
      harbor-wide concentration of mercury has decreased to 0.7-0.8ppm, a level that is
      approaching the pre-industrial background level. Nevertheless, in certain areas
      of the harbor, there remain sufficiently high concentrations of contaminants to
      merit concern and to create serious problems for sponsors of dredging projects.
      Development of a basin-wide sediment management strategy is necessary to guide
      port decision-makers in their efforts to clean-up contaminant sources, to dredge
      regional waterways, and to ameliorate the contaminated sediment disposal problem.
      The backbone of this strategy is the integration of the data from an ongoing
      field monitoring and modeling program with a parallel investigation of watershed
      and airshed sources and sinks using industrial ecology methodology.

PMID- 11463501
TI  - Dredging and disposal of fine sediments in the state of Rio de Janeiro, Brazil.
AB  - Dredging is employed quite frequently in the state of Rio de Janeiro, especially
      for the installation and upkeep of commercial ports and rehabilitation of the
      hydraulic section of silted bodies of water. Until recently, all dredged material
      with no economic use was destined for marine disposal or stored at the edge of
      the water body. Since the 1990s, however, a new approach has been adopted for
      dredging as a result of pressure from the environmental organisations,
      encouraging closer interaction in Rio de Janeiro between the local and state
      public authorities and the universities on issues relating to licensing of this
      kind of activity. The recent experiments of the Civil and Ocean Engineering
      Programs of COPPE-UFRJ (Federal University of Rio de Janeiro) described herein
      are included in this context. The state of Rio de Janeiro has three bays, several
      coastal lagoon systems and a number of small and medium sized rivers in or close
      to urban areas, with a gentle slope as they near the sea. This is, then, a region
      highly susceptible to silting processes of water bodies, and therefore, to
      maintenance and/or environmental rehabilitation. As discussed in the article,
      fine and almost always organic sediments prevail, which is a considerable
      obstacle to the end disposal and possibility of reuse.

PMID- 11463502
TI  - Recovery of dredged material for beneficial use: the future role of physical
      separation processes.
AB  - Sediments dredged from navigational waterways have historically been disposed in
      confined disposal facilities (CDFs) or in open water. When sediments are
      contaminated, open water disposal is typically not an alternative, and sediments
      are placed in CDFs. Many CDFs are nearing capacity, and siting and constructing
      new facilities is both difficult and expensive. In many cases, CDFs contain both
      clean and contaminated dredged material. Removal of materials suitable for
      beneficial use (BU) is one alternative under consideration to extend the life of
      existing CDFs, as is separation of recoverable materials at the time of disposal.
      Several technologies for recovery of clean materials or treatment of contaminated
      materials for beneficial use are presently under evaluation. Physical separation
      technologies have been demonstrated to have potential in reducing the volume of
      sediment that must be managed with confined disposal, but there are several
      technical issues that remain to be addressed. Determination of beneficial use
      specifications, physical and chemical characterization of dredged material,
      overall site characterization, selection of suitable unit operations, management
      of liquid and solid residuals, and cost/benefit analysis, are all important
      aspects to successful implementation of separation processes. Several of these
      elements are presently being evaluated in research conducted by the US Army Corps
      of Engineers, at the ERDC Waterways Experiment Station (WES).

PMID- 11463503
TI  - Determination of the environmental impact of consolidation induced convective
      transport through capped sediment.
AB  - The presence of contaminated sediment poses a barrier to essential waterway
      maintenance and construction in many ports and harbors, which support 95% of US
      foreign trade. Cost effective solutions to remediate contaminated sediments in
      waterways need to be applied. Capping is the least expensive remediation
      alternative available for marine sediments that is unsuitable for open water
      disposal. Dredged material capping and in situ capping alternatives, however, are
      not widely used because regulatory agencies are concerned about the potential for
      contaminant migration through the caps. Numerous studies have been conducted on
      the effects of diffusion through caps, however, there is a lack of experimental
      data documenting the effects of consolidation induced transport of contaminants
      through caps. This study examines consolidation induced convective contaminant
      transport in capped sediment utilizing a research centrifuge. In this study,
      consolidation induced convective transport was modeled for 7h at 100 x g, which
      modeled a contaminant migration time of 8 years for a prototype that was 100
      times larger than the centrifuge model. In this study, hydrodynamic dispersion
      was a function of the seepage velocity. And, advection and dispersion dominated
      the migration of contaminants. Centrifuge model results were compared to an
      analytical solution for advection and dispersion. The advection-dispersion
      equation demonstrated that the centrifuge test is a conservative estimate for
      predicting contaminant transport. In conducting sensitivity analysis of the
      advection-dispersion equation to the centrifuge modeling, as hydrodynamic
      dispersion decreased, the time for contaminant breakthrough increased. Moreover,
      as the sediment to water distribution coefficient increased, the contaminant
      concentration into the overlying water decreased.

PMID- 11463504
TI  - Ultrasound to decontaminate heavy metals in dredged sediments.
AB  - Sediments contaminated with heavy metals due to past disposal practices threaten
      the environment and require remediation. This study was an attempt to develop a
      technology to decontaminate heavy metals in dredged sediments using ultrasound
      coupled with vacuum pressure. A set of laboratory scale experiments were
      conducted using dredged sediments obtained from New York/New Jersey harbor. This
      sediment sample is considered as category III, a material that failed to meet
      USEPA requirements for toxicity or bioaccumulation, and required secure disposal.
      Acoustic cavitation due to ultrasound energy coupled with vacuum pressure was
      used to facilitate the removal of chromium (the selected metal contaminant) from
      the sediments. Full factorial experimental designs were performed to evaluate the
      above treatment technique and to optimize the processes. Two coupled processes
      were used to separate and to treat both coarse (Process #1) and fine (Process #2)
      fractions of sediments. Selected variables for evaluation of Process #1 were
      ultrasound power, soil-to-water ratio, vacuum pressure and dwell time, and for
      Process #2 were ultrasound power, soil-to-water ratio and dwell time. Laboratory
      scale experiments were carried out with various combinations of these parameters
      according to the factorial design. The optimum removal was found to be 92% with
      the parameter levels at 1200W power, 1:15 soil-to-water ratio, 15 psi vacuum
      pressure and 15 min of dwell time. After the application of Process #2 for fine
      sediments it was found that the fines were separated into silt and clay. Only the
      silt faction had a considerable metal removal while the clay fraction was
      insensitive to the treatment. A maximum removal of 83% was obtained for silt
      fraction when factor levels were at 1200W power, 1:50 soil-to-water ratio and 90
      min of dwell time. Further analysis of clay fraction showed that the chromium in
      clay is immobile and stable. The toxicity characteristic leaching procedure
      (TCLP) test on clay fraction confirmed that the treated clay fraction is safe to
      dispose. The study showed that the proposed treatment technique is effective and
      economical for sediments with lower clay contents.

PMID- 11463505
TI  - Analysis of electrokinetic sedimentation of dredged Welland River sediment.
AB  - The Welland River is a tributary of the Niagara River. In the late 1980s it was
      discovered that a section of the Welland River was contaminated with heavy metals
      as a results of two sewer outfalls that has been used by a steel plant and local
      industrial and municipal operations for the last 50-60 years. One of the major
      problems encountered in the treatment of the dredged Welland River sediment is a
      slow rate of sedimentation due to the large proportion of fine solids in the
      sediment. In this study, the results of electrokinetic sedimentation of the
      Welland River sediment are analyzed based on the principles of gravitational and
      electrokinetic sedimentation. It was found that the effects of electric field
      intensity and the initial solid concentration of the suspension are the
      dominating factors governing the average particle settling velocity, the
      coefficient of free settling in the free settling stage and the coefficient of
      sedimentation in the hindered settling stage. The electrokinetic treatment is
      proven to be effective in terms of increasing the free and hindered settling
      velocities, reducing the overall sedimentation time and increasing the final
      solid concentration of the sediment. Thus, electrokinetics can be used to
      accelerate sedimentation of dilute solid suspensions, such as dredged sediment,
      wastewater and mine tailings.

PMID- 11463506
TI  - Heavy metal removal from sediments by biosurfactants.
AB  - Batch washing experiments were used to evaluate the feasibility of using
      biosurfactants for the removal of heavy metals from sediments. Surfactin from
      Bacillus subtilis, rhamnolipids from Pseudomonas aeruginosa and sophorolipid from
      Torulopsis bombicola were evaluated using a metal-contaminated sediment (110mg/kg
      copper and 3300mg/kg zinc). A single washing with 0.5% rhamnolipid removed 65% of
      the copper and 18% of the zinc, whereas 4% sophorolipid removed 25% of the copper
      and 60% of the zinc. Surfactin was less effective, removing 15% of the copper and
      6% of the zinc. The technique of ultrafiltration and zeta potential measurements
      were used to determine the mechanism of metal removal by the surfactants. It was
      then postulated that metal removal by the biosurfactants occurs through sorption
      of the surfactant on to the soil surface and complexation with the metal,
      detachment of the metal from the soil into the soil solution and hence
      association with surfactant micelles. Sequential extraction procedures were used
      on the sediment to determine the speciation of the heavy metals before and after
      surfactant washing. The carbonate and oxide fractions accounted for over 90% of
      the zinc present in the sediments. The organic fraction constituted over 70% of
      the copper. Sequential extraction of the sediments after washing with the various
      surfactants indicated that the biosurfactants, rhamnolipid and surfactin could
      remove the organically-bound copper and that the sophorolipid could remove the
      carbonate and oxide-bound zinc. Therefore, heavy metal removal from sediments is
      feasible and further research will be conducted.

PMID- 11463507
TI  - Dredged material decontamination demonstration for the port of New York/New
      Jersey.
AB  - Management of contaminated dredged material is a significant challenge in the
      Port of New York and New Jersey as a result of more stringent regional ocean
      placement regulations with escalating costs for upland placement. One component
      of an overall management plan can be the application of a decontamination
      technology followed by creation of a product suitable for beneficial use. This
      concept is the focus of a project now being carried out by the US Environmental
      Protection Agency, Region 2, the US Army Corps of Engineers, New York District,
      the US Department of Energy, Brookhaven National Laboratory, and regional
      university groups that have included Rensselaer Polytechnic Institute, Rutgers
      University, New Jersey Institute of Technology, and Stevens Institute of
      Technology. The project has progressed through phased testing of commercial
      technologies at the bench scale (15 liters) (Marcor, Metcalf & Eddy, Gas
      Technology Institute, Westinghouse Science & Technology, BioGenesis,
      International Technology, and BioSafe) and pilot-scale (1.5-500m(3)) (BioGenesis,
      Gas Technology Institute, and Westinghouse Science & Technology) levels. The
      technologies developed by Gas Technology Institute and BioGenesis are now going
      forward to commercial demonstration facilities that are intended to treat from
      23000 to 60000m(3) of dredged material during their first operational period in
      2001-2002. Beneficial use products are soils and cement. Treatment costs for the
      final commercial facilities are estimated at US$ 39 per m(3). Selection of the
      technologies was made based on the effectiveness of the treatment process,
      evaluation of the possible beneficial use of the treated materials, and other
      factors. Major elements of the project are summarized here.

PMID- 11463508
TI  - An evaluation of technologies for the heavy metal remediation of dredged
      sediments.
AB  - Sediments dewatering is frequently necessary after dredging to remediate and
      treat contaminants. Methods include draining of the water in lagoons with or
      without coagulants and flocculants, or using presses or centrifuges. Treatment
      methods are similar to those used for soil and include pretreatment, physical
      separation, thermal processes, biological decontamination,
      stabilization/solidification and washing. However, compared to soil treatment,
      few remediation techniques have been commercially used for sediments. In this
      paper, a review of the methods that have been used and an evaluation of developed
      and developing technologies is made. Sequential extraction technique can be a
      useful tool for determining metal speciation before and after washing.
      Solidification/stabilization techniques are successful but significant monitoring
      is required, since the solidification process can be reversible. In addition, the
      presence of organics can reduce treatment efficiency. Vitrification is applicable
      for sediments but expensive. Only if a useful glass product can be sold will this
      process be economically viable. Thermal processes are only applicable for removal
      of volatile metals, such as mercury and costs are high. Biological processes are
      under development and have the potential to be low cost. Since few low cost metal
      treatment processes for sediments are available, there exists significant demand
      for further development. Pretreatment may be one of the methods that can reduce
      costs by reducing the volumes of sediments that need to be treated.

PMID- 11463510
TI  - Repeated administration of the novel antiepileptic agent levetiracetam does not
      alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers.
AB  - OBJECTIVE: This study was undertaken to determine whether levetiracetam (Keppra)
      affected the pharmacokinetic or pharmacodynamic profile of digoxin in healthy
      adults. METHODS: Seven men and four women (19-48 years old) completed this double
      blind, placebo-controlled study. Each received digoxin 0.25 mg once daily (0.5 mg
      on day 1) during the 1-week run-in period, followed by two 1-week periods of
      coadministration of digoxin with levetiracetam (2000 mg/day) or placebo in a two
      way crossover design. The pharmacokinetics of digoxin and levetiracetam were
      assessed by analysis of blood samples. ECG recordings were taken to monitor
      effects of levetiracetam on digoxin pharmacodynamics. RESULTS: The ratios of
      geometric means, using a 90% confidence interval, between coadministration of
      digoxin with levetiracetam or placebo were 103.96% (99.18%, 108.95%) for AUC(ss),
      100.87% (89.52%, 113.66%) for C(max), 97.67% (82.76%, 115.26%) for PTF, and
      99.04% (90.98%, 109.00%) for C(min). Although digoxin produced predictable
      changes in ECG, its pharmacodynamic parameters did not differ significantly
      between levetiracetam and placebo administration. Furthermore, the
      pharmacokinetics of levetiracetam were not altered in the presence of digoxin. Co
      administration of levetiracetam and digoxin was well tolerated. CONCLUSION: At
      the doses administered, there was no pharmacokinetic interaction and no evidence
      of a pharmacodynamic interaction between digoxin and levetiracetam.

PMID- 11463511
TI  - Effect of riluzole on the acquisition and expression of amygdala kindling.
AB  - PURPOSE: Riluzole possesses various synaptic effects including an inhibitory
      action on glutamate release. The drug has been shown to inhibit kindled seizures,
      while its effect on the acquisition of kindling has not been reported. We
      investigated effects of riluzole on the kindling development in addition to
      effects on kindled seizures. METHODS: A bipolar electrode was implanted in the
      right amygdala of rats. Riluzole was injected intraperitoneally 30 min before
      kindling stimulation. To investigate effects of riluzole on the kindling
      development, rats were stimulated once daily for the drug session of 14 days at a
      current of 200 microA, 60 Hz, 1 ms for 2 s and thereafter stimulated without
      drugs (drug-free session) until completion of kindling. Seizure ranks and after
      discharge duration were observed every day. To investigate effects of riluzole on
      kindled seizures, fully-kindled rats were stimulated at the current of
      generalized seizure threshold (GST) before and after the administration of
      riluzole. Seizure ranks and after discharge duration were measured. GST after the
      treatment was also determined. RESULTS: The number of stimuli required for the
      first appearance of stage five seizure was significantly larger in rats treated
      with 8 mg/kg of riluzole than in vehicle controls. Riluzole at a dose of 8 mg/kg
      significantly retarded the development of seizure stages in the drug session. By
      comparison, effects on the duration of after discharge was relatively mild,
      though significantly different from the vehicle control. Riluzole at a dose of
      either 4 or 8 mg/kg markedly inhibited behavioral seizures and reduced the
      duration of after discharge in kindled seizures provoked by GST. The drug also
      significantly increased GST at both doses, suggesting that the anticonvulsant
      effects were attributed to the increase in GST. CONCLUSION: It was demonstrated
      that inhibitory effects of riluzole on both kindled seizures and the development
      of behavioral seizures in kindling acquisition with relatively mild correlation
      to afterdischarge duration. These effects might be attributed to inhibitory
      actions of riluzole on glutamate release and NMDA-receptor mediated events.

PMID- 11463512
TI  - Repeated low-dose treatment of rats with pilocarpine: low mortality but high
      proportion of rats developing epilepsy.
AB  - Systemic administration of pilocarpine in rats can result in a chronic behavioral
      state that is similar to human temporal lobe epilepsy. The pilocarpine model of
      epilepsy is widely used for studying the factors that contribute to the
      development of epilepsy as a consequence of status epilepticus (SE). For this
      purpose, pilocarpine is either administered alone at a high systemic dose or in
      combination with lithium, which markedly potentiates the convulsant effect of
      pilocarpine. Both experimental protocols, however, are associated with high
      mortality rates. In the present study, we evaluated whether mortality rate in
      rats can be decreased by repeated administration of low doses of pilocarpine. The
      time the rats spent in SE was limited by diazepam. Preliminary experiments in
      lithium-free rats indicated that repeated low-dose administration of pilocarpine
      is too time-consuming to produce SE compared to single high-dose administration.
      All subsequent experiments were performed in lithium-pretreated rats. Single-dose
      injection of 30 mg/kg pilocarpine produced SE in approximately 70% of the
      animals, but 45% of the rats died although SE was interrupted by diazepam after
      90 min. Repeated i.p. administration of 10 mg/kg pilocarpine at 30-min intervals
      resulted in SE after 2-4 injections; the mean dose of pilocarpine needed to
      induce SE was 26 mg/kg. When SE was interrupted after 90 min, mortality rate was
      below 10%, which was significantly lower compared to the protocol with one single
      administration of 30 mg/kg pilocarpine. In contrast to mortality rate, the
      development of spontaneous recurrent seizures did not differ between experimental
      protocols. Almost all rats which had experienced a SE of at least 60 min
      developed chronic epilepsy. Average latency to the first spontaneous seizure was
      approximately 40 days. The frequency and severity of spontaneous seizures was not
      significantly different between protocols, although animal groups with repeated
      low-dose treatment tended to have higher frequencies of spontaneous seizures
      compared to single-dose administration. The present study demonstrates that
      systemic treatment of lithium-pretreated rats with several low doses of
      pilocarpine efficiently produces SE and chronic epilepsy with much lower
      mortality rates than single-dose pilocarpine.

PMID- 11463513
TI  - Superoxide dismutase, glutathione peroxidase activities and the hydroperoxide
      concentration are modified in the hippocampus of epileptic rats.
AB  - The relationship between free radical and scavenger enzymes has been found in the
      epileptic phenomena and reactive oxygen species have been implicated in seizure
      induced neurodegeneration. Using the epilepsy model obtained by systemic
      administration of pilocarpine (PILO) in rats, we investigated the superoxide
      dismutase (SOD) and glutathione peroxidase (GPx) activities as well as the
      hydroperoxide (HPx) concentration in the hippocampus of rats during status
      epilepticus (SE), silent and chronic periods. The enzyme activities as well as
      the HPx concentration were measured using spectrophotometric methods and the
      results compared to values obtained from saline-treated animals. The SOD activity
      decreased after long-lasting SE period and during the chronic phase. In addition,
      HPx levels increased in same periods whereas the GPx activity increased only in
      the hippocampus of animals submitted to 1 h of SE. Animals presenting partial
      seizures, those submitted to 5 h of SE and animals from the silent period
      (seizure free) showed normal levels of SOD, GPx and HPx. These results show a
      direct evidence of lipid peroxidation during seizure activity that could be
      responsible for neuronal damage in the hippocampus of rats, during the
      establishment of PILO model of epilepsy.

PMID- 11463514
TI  - High prevalence of antiphospholipid antibodies in children with epilepsy: a
      controlled study of 50 cases.
AB  - Evidence of immune system aberrations in patients with epilepsy includes
      antiphospholipid antibody positivity in adult patients with epilepsy with a
      prevalence of 19-26% and in 13% of children with partial epilepsy. Also
      immunoglobulin A deficiency has been reported to exist in up to 25% of epilepsy
      patients. The possible role of immune mechanisms in the pathogenesis of childhood
      epilepsy is clinically supported by the effectiveness of immunomodulatory
      treatments in cases with catastrophic childhood epilepsies. We analyzed a set of
      various autoantibodies in 50 consecutive children with epilepsy and in 20 healthy
      control subjects. None of the children had any clinical signs of immune system
      disorders. The main result was a significantly (P=0.011) higher prevalence of
      antiphospholipid antibodies in the study group (44%) compared with controls
      (10%). These antibodies were unexpectedly common (71-80%) in children with
      multiple seizure types associated often with symptomatic etiology, early onset
      and high frequency of seizures. There was no evidence of the antiphospholipid
      positivity being induced by certain AEDs (e.g. phenytoin or carbamazepine). Even
      though the significance of these autoantibodies remains unknown, their increased
      prevalence indicates that immune system mediated mechanisms may have a role in
      the manifestation of epilepsy in some children.

PMID- 11463515
TI  - T-STAR gene: fine mapping in the candidate region for childhood absence epilepsy
      on 8q24 and mutational analysis in patients.
AB  - Childhood absence epilepsy (CAE) is one of the most common epilepsies in
      children. At least four phenotypic subcategories of CAE have been proposed. Among
      them, a subtype persisting with tonic-clonic seizures has been mapped to 8q24
      (ECA1 MIM 600131). By constructing a physical map for the 8q24 region, we
      recently narrowed the ECA1 locus to a 1.5-Mb region. In the present
      communication, we show that T-STAR gene is located within the ECA1 region. T-STAR
      is a novel member of STAR (for signal transduction and activation of RNA) family,
      and is predicted to encode a spermatogenesis related RNA-binding protein. T-STAR
      is located within the markers D8S2049 and D8S1753 and its complete coding region
      spans nine exons. In addition to its known expression in testis, moderate level
      of transcripts for T-STAR gene was detected in brain, heart and is highly
      abundant in skeletal muscle. Mutational analysis for the T-SATR gene in CAE
      families did not show any sequence variation in the coding region, and this
      suggests that the T-STAR gene is not involved in the pathogenesis of persisting
      CAE. However, genomic organization of T-STAR gene characterized in the present
      report might help in understanding the biological functions of T-STAR as well as
      its suspected involvement in other disorders mapped on this region.

PMID- 11463516
TI  - A comparison of monotherapy with lamotrigine or carbamazepine in patients with
      newly diagnosed partial epilepsy.
AB  - Monotherapy with lamotrigine or carbamazepine was evaluated in a multicentre open
      trial of patients aged 2 years and above with newly diagnosed partial epilepsy. A
      total of 417 patients were randomised to treatment with lamotrigine, while 201
      patients received carbamazepine. Following a dose escalation period of 6 weeks,
      maintenance therapy (Weeks 7-24) was adjusted according to response. Efficacy was
      similar with both treatments (65% with lamotrigine, 73% with carbamazepine,
      P=0.085). Efficacy was assessed by the proportion of patients seizure free during
      the last 16 weeks of treatment; all subjects who remained in the study for at
      least 18 weeks after the week 4 visit were included in the analysis. More
      patients receiving lamotrigine completed the study (81%), compared with those
      receiving carbamazepine (77%). This difference was primarily due to
      discontinuation as a result of adverse events, reported by 34 (8%) of those
      treated with lamotrigine but 26 (13%) of those treated with carbamazepine. The
      proportion of patients who experienced adverse events in the lamotrigine group
      was lower (218 patients, 52%) compared with the carbamazepine group (120
      patients, 60%). The proportion of patients with adverse events considered to be
      drug related was lower in the lamotrigine group (132 patients, 32%) compared with
      the carbamazepine group (83 patients, 41%). Somnolence was the only adverse event
      reported at an incidence of greater than 5% and where there was a difference of
      5% or more between treatment groups (4% lamotrigine, 11% carbamazepine patients).
      The small subsets of elderly patients (aged 65 years or over) and paediatric
      patients (aged 2-12 years) also showed better tolerability to lamotrigine than to
      carbamazepine. In conclusion, monotherapy with lamotrigine is as effective as
      carbamazepine in patients with newly diagnosed partial epilepsy. Patients were
      able to tolerate lamotrigine better than carbamazepine, so more patients
      receiving lamotrigine were able to remain on therapy.

PMID- 11463517
TI  - Polymorphism analysis of JRK/JH8, the human homologue of mouse jerky, and
      description of a rare mutation in a case of CAE evolving to JME.
AB  - Disruption of the function of the mouse jerky gene by transgene insertion causes
      generalized recurrent seizures reminiscent of human idiopathic generalized
      epilepsy (IGE). A human homologue, JRK/JH8, has been cloned, which maps to 8q24,
      a chromosomal region associated with several forms of IGE. JRK/JH8 is, therefore,
      a candidate locus for at least some forms of IGE. We report corrected cDNA
      sequences and extended open reading frames for the mouse jerky and human JRK/JH8
      genes, which add 48 amino acids to the N-terminus of the Jerky protein and which
      extends the region of homology with the N-terminal DNA-binding domain of the
      centromere-binding protein, CENP-B. Systematic sequencing of the coding region of
      the extended JRK/JH8 gene identified single nucleotide polymorphisms that define
      three haplotypes, which were used for association studies in patients with
      idiopathic generalized epilepsy. We report one subject with childhood absence
      epilepsy (CAE) that evolved to juvenile myoclonic epilepsy (JME) that has a
      unique de novo mutation that results in a non-conservative amino acid change at a
      potential protein glycosylation site. Familial analysis supports a causal role
      for this mutation in the disease.

PMID- 11463518
TI  - The insular but not the perirhinal cortex is involved in the expression of fully
      kindled amygdaloid seizures in rats.
AB  - We have previously reported an important excitatory role of the perirhinal cortex
      (PRC) in rat kindling development using an immunohistochemistry technique. In
      this study, we investigated the roles of the PRC and the insular cortex (INS)
      located rostral to the PRC, in fully-kindled amygdaloid seizures, using a
      microinjection technique in the rat kindling model of epilepsy. Following the
      establishment of daily kindling, we investigated the effects of microinjections
      of procaine hydrochloride, 2-amino-5-phosphonovalerate (APV; an N-methyl-D
      aspartate (NMDA) receptor antagonist) and 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(f)-quinoxaline (NBQX; an alpha-amino-3-hydroxy-5-methyl-isoxazole-4
      propionic acid (AMPA) receptor antagonist). Microinjections of these drugs into
      the ipsilateral PRC did not suppress kindled seizures. The possibility is that
      the process of kindling development forms novel seizure-generalization pathways
      that do not require further activation of the PRC. On the other hand, procaine
      and APV injected into the ipsilateral INS significantly suppressed kindled
      seizures. The manner of suppression appeared to be 'all or none'. It is therefore
      possible that at least the activation of NMDA receptors in the INS is necessary
      to express generalized kindled amygdaloid seizures.

PMID- 11463519
TI  - Expression of metabotropic glutamate receptor 1alpha in the hippocampus of rat
      pilocarpine model of status epilepticus.
AB  - The expression of metabotropic glutamate receptor 1alpha was studied in the rat
      hippocampus after pilocarpine-induced status epilepticus by Western blot and
      immunocytochemistry at both light and electron microscopic levels. At 1 day after
      pilocarpine-induced status epilepticus, there was marked decrease in metabotropic
      glutamate receptor 1alpha immunoreactivity at the border between stratum oriens
      and alveus in CA1 and CA3, and in the hilus of dentate gyrus. Between 3 and 31
      days after pilocarpine-induced status epilepticus, metabotropic glutamate
      receptor 1alpha-immunoreactive dendrites and cell bodies in the border between
      stratum oriens and alveus gradually reappeared. Upregulation of metabotropic
      glutamate receptor 1alpha, however, was observed in the stratum oriens of CA1 at
      day 1, but returned to baseline by day 7. By electron microscopy, the
      metabotropic glutamate receptor 1alpha-immunoreactive product was demonstrated
      only in the post-synaptic elements in the border between the stratum oriens and
      alveus of CA1 and the hilus of the dentate gyrus in both control and experimental
      rats. At 1 day after pilocarpine-induced status epilepticus, metabotropic
      glutamate receptor 1alpha-immunoreactive degenerating neurons were identified in
      the border between stratum oriens and alveus of CA1 and the hilus of the dentate
      gyrus. At 7 and 31 days, many degenerating axons were also found. Present results
      suggest that excitoneurotoxicity mediated through post-synaptic metabotropic
      glutamate receptor 1alpha may be involved in degeneration and death of
      interneurons in the hilus of dentate gyrus, and the border between stratum oriens
      and alveus of CA1 in the early stage after pilocarpine-induced status
      epilepticus.

PMID- 11463520
TI  - A retrospective review of 228 episodes of infective endocarditis where rheumatic
      valvular disease is still common.
AB  - Two hundred and twenty-eight episodes of infective endocarditis in adult patients
      (mean age 36 years) were reviewed retrospectively. There were 183 episodes (80%)
      of native valve, 15 (7%) early prosthetic valve and 30 (13%) late prosthetic
      valve endocarditis. The most common predisposing factor was rheumatic valvular
      disease (65%). None of the patients were intravenous drug users. According to the
      Duke criteria, the number of definite, probable and rejected episodes were 121
      (53%), 94 (41%) and 13 (6%), respectively. Additional minor criteria increased
      the number of definite endocarditis to 82%. The Duke criteria are not primarily
      intended to influence treatment decisions but are helpful in standardising
      research activities. The choice of the level of sensitivity or specificity of the
      criteria may be adjusted according to the aim of the study and prevalence of
      disease in a particular area. More sensitive criteria may be valuable in those
      countries where the prevalence of rheumatic valvular disease is still high.

PMID- 11463521
TI  - Bacteriological and clinical efficacy of various antibiotics used in the
      treatment of streptococcal pharyngitis in Italy. An epidemiological study.
AB  - A total of 123 community paediatricians and 23 microbiology laboratories studied
      the clinical and bacteriological efficacy of treatment of group A streptococcal
      pharyngitis in Italy. Of 1065 patients, from whom Streptococcus pyogenes was
      isolated, 723 returned to follow up and of these 138 (19%) still had a positive
      throat culture. The erythromycin resistance (ER) rate was 23.7% with resistance
      phenotype distribution of: 31.7% constitutive (CR), 26.6% inducible (IR) and
      41.7% efflux pump (M) resistance phenotype. All strains were susceptible to the
      beta-lactam agents tested. CR strains were highly resistant to all 14, 15 and 16
      membered macrolides with the exception of rokitamycin which showed activity
      against 37.8% of isolates. All phenotype M and some IR isolates were susceptible
      to clindamycin, rokitamycin, josamycin and spiramycin; clarithromycin was active
      against a small percentage of strains belonging to the IR and M phenotype.
      Bacterial eradication was found in 85.5, 78.7 and 75.8% of the penicillin,
      macrolide and cephalosporin treated groups. Genotyping of strains showed that
      8.7% of the 19% of cases classified as 'failed bacterial eradication' were due to
      recolonization with a different isolate, observed exclusively among beta-lactams
      treated patients. Clinical cure was achieved in a high percentage of cases,
      irrespective of the antibiotic prescribed, with the best clinical efficacy being
      found following therapy with amoxycillin and clarithromycin (90.9%).

PMID- 11463522
TI  - Efficacy and safety of gemifloxacin 320 mg once-daily for 7 days in the treatment
      of adult lower respiratory tract infections.
AB  - An open-label, non-comparative study assessed the clinical and bacteriological
      efficacy of gemifloxacin (320 mg, once-daily for 7 days) in lower respiratory
      tract infections (LRTI). Patients with acute exacerbation of chronic bronchitis
      (AECB, n=261) or community-acquired pneumonia (CAP, n=216) were enrolled into the
      study. Clinical success rates at follow-up (days 21-28) in the intent-to-treat
      (ITT) population were high, 83.1% in AECB patients (95% CI: 77.9, 87.4) and 82.9%
      in CAP patients (95% CI: 77.0, 87.5). High bacteriological success rates were
      achieved (bacteriological ITT population), 91.2% (52/57) in AECB patients (95%
      CI: 80.0, 96.7) and 77.9% (60/77) in CAP patients (95% CI: 66.8, 86.3).
      Gemifloxacin was well tolerated with a low incidence of adverse events.
      Gemifloxacin treatment resulted in high clinical and bacteriological success
      rates and is a well-tolerated therapy for the treatment of LRTIs.

PMID- 11463523
TI  - GAR-936 (9-t-butylglycylamido-minocycline) susceptibility test development for
      streptococci, Haemophilus influenzae and Neisseria gonorrhoeae: preliminary
      guidelines and interpretive criteria.
AB  - GAR-936, a new semisynthetic derivative of minocycline, has earlier shown
      promising activity against tetracycline-resistant pathogens, including
      Streptococcus pneumoniae. In this study, the activity of GAR-936 was tested
      against a total of 514 tetracycline-susceptible and -resistant strains of S.
      pneumoniae, beta-haemolytic streptococci, viridans group streptococci,
      Haemophilus influenzae and Neisseria gonorrhoeae. All strains of H. influenzae,
      were inhibited by < or =2 mg/l of GAR-936, with MIC(90)s for all streptococci and
      gonococci of < or =0.5 mg/l. Scattergrams of GAR-936 comparing MICs by broth
      microdilution testing and zone diameters using 30 microg disks, confirmed the
      proposed susceptibility criteria of < or 2 mg/l or > or =20 mm zone diameter.
      Clinical trial results should be correlated with these preliminary in vitro
      results to confirm and/or adjust these susceptibility interpretive criteria for
      GAR-936 when testing fastidious streptococci, H. influenzae and N. gonorrhoeae.

PMID- 11463524
TI  - Antibiotic resistance in Salmonella enterica subsp. enterica strains isolated in
      Poland from 1998 to 1999.
AB  - A total of 326 Salmonella enterica subsp. enterica strains representing 29
      serotypes, isolated from human stool specimens during 1998-1999 in sanitary
      epidemiological units in Poland were tested for antibiotic susceptibility by a
      standard disk diffusion method. The antibiotics used were ampicillin, cefotaxime,
      chloramphenicol, tetracycline, streptomycin, gentamicin, kanamycin, nalidixic
      acid, ciprofloxacin, furazolidone, cotrimoxazole, sulphonamides and trimethoprim.
      In addition, 201 strains belonging to the five most commonly isolated serotypes
      (S. Enteritidis, S. Typhimurium, S. Hadar, S. Infantis and S. Virchow) also had
      minimal inhibitory concentrations (MICs) determined for amoxycillin/clavulanic
      acid. Selected strains were screened for production of extended spectrum beta
      lactamases (ESBLs). There were 49.4% of Salmonella enterica subsp. enterica
      strains resistant to two or more antibiotics, with the highest prevalence of
      multiple resistant strains among serotypes Typhimurium, Hadar and Virchow.
      Resistance to ampicillin, streptomycin, tetracycline, nalidixic acid,
      furazolidone and sulphonamides occurred most frequently. Over 93% of S. Virchow
      strains were resistant to furazolidone. No strains resistant to ciprofloxacin by
      disk-diffusion method were detected but 31.3% of isolates of the 201 strains
      representing the five most common serotypes had reduced ciprofloxacin
      susceptibility (MICs ranging 0.125-0.5 mg/l). One strain (S. Mbandaka) was
      resistant to cefotaxime and produced ESBL.

PMID- 11463525
TI  - Comparative killing kinetics of the novel des-fluoro(6) quinolone BMS-284756,
      fluoroquinolones, vancomycin and beta-lactams.
AB  - The primary bactericidal classes used therapeutically as single agents, are the
      quinolones and the cell-wall active agents. In this study, their rates of killing
      were compared. The des-fluoro(6) quinolone BMS-284756 (T-3811ME),
      fluoroquinolones (trovafloxacin, levofloxacin) and cell wall-active agents (beta
      lactams, vancomycin) were evaluated against Enterobacteriaceae, Staphylococcus
      aureus, streptococci, and Enterococcus faecalis. Time-kill analysis was done at
      10x the MIC, using Mueller-Hinton broth (supplemented with 7% lysed horse blood
      for Streptococcus pneumoniae and the viridans streptococci), or Brain Heart
      Infusion broth for beta-haemolytic streptococci. Using a 3-log(10) decrease in
      viable count as an index of bactericidal activity, BMS-284756 and the
      fluoroquinolones killed Enterobacteriaceae rapidly, requiring < 2 h versus > or
      =6 h for beta-lactams. The staphylococcal cell counts generally decreased more
      rapidly with quinolone exposure, compared with those treated with vancomycin or
      the beta-lactams. The antimicrobial agents killed streptococci and enterococci
      more slowly, requiring > 6 h to decrease the viable count by 99.9%. In summary,
      BMS-284756 killing rates are similar to those of recent fluoroquinolones and are
      bacterial group-dependent. Overall, the quinolones are more rapidly bactericidal
      than vancomycin and the beta-lactam antibiotics.

PMID- 11463526
TI  - Comparative in vitro bacteriostatic and bactericidal activity of trovafloxacin,
      levofloxacin and moxifloxacin against clinical and environmental isolates of
      Legionella spp.
AB  - The susceptibility of 140 Legionella spp isolates (106 clinical and 34
      environmental isolates) to trovafloxacin (TRFX), levofloxacin (LEVX),
      moxifloxacin (MOFX), ciprofloxacin (CIPX), ofloxacin (OFLX), erythromycin (ERY),
      azithromycin (AZI) and rifampicin (RIF) was studied using a standard
      microdilution method and buffered yeast extract broth (BYE) supplemented with
      0.1% alpha-ketoglutarate. The post-antibiotic effects (PAEs) of the study drugs
      against 10 clinical isolates of Legionella pneumophila sg.1 were compared. The
      MIC inhibiting 90% of strains tested on BYEalpha broth were 0.008, 0.016, 0.016,
      0.06, 0.125, 0.5, 0.5, and 0.004 mg/l for TRFX, LEVX, MOXX, CIP, OFLX, ERY, AZI,
      and RIF, respectively. The MBC/MIC ratios ranged from one to eight depending on
      the antibiotic tested: TRFX [1x-2 x MIC], LEVX, MOFX, CIPX and OFLX [1x-4 x MIC],
      RIF [2x-4 x MIC], ERY and AZI [2x-8 x MIC]. TRFX, RIF, LEVX, MOFX, CIPX, OFLX,
      ERY and AZI showed similar activity against Legionella species other than L.
      pneumophila. One-hour exposures to the study antimicrobial agents at a
      concentration of 4 x MIC resulted in PAEs as follows (average in hours): TRFX:
      2.68 h; RIF: 2.63 h; CIPX: 2.62 h; MOFX: 2.56 h; LEVX: 2.41 h; OFLX: 2.25 h; AZI:
      1.65 h; and ERY: 1.54 h. In conclusion, our in vitro data confirm that
      trovafloxacin, levofloxacin, moxifloxacin and rifampicin have excellent
      bacteriostatic and bactericidal activity against Legionella spp and show
      significant post-antibiotic effect.

PMID- 11463527
TI  - Elucidation of antibiotic effectiveness against Staphylococcus epidermidis during
      intraocular lens implantation.
AB  - The effect of various antimicrobial agents commonly used in irrigating solutions
      on the hydrophobicity and adherence of Staphylococcus epidermidis ATCC 14990 was
      investigated. The longest post-antibiotic effect (PAE=3.2 h) was obtained with
      gentamicin followed by ciprofloxacin (2.7 h), clindamycin (2.2 h), ceftazidime
      (1.8 h) and vancomycin (1.6 h). The post-antibiotic effect on surface
      hydrophobicity of cells previously treated with gentamicin, ciprofloxacin, or
      clindamycin for 120 min resulted in a substantial decrease in affinities to
      hexadecane (31.4, 28.5 and 27%, respectively) compared with control untreated
      cells. Less effect was noted with cells previously treated with ceftazidime or
      vancomycin (20.5 and 15.8%, respectively). Similar but less marked results were
      obtained when the cells were exposed to antibiotics for 30 or 60 min. The post
      antibiotic effect on adherence of cells to both intraocular lenses and to
      epithelial cells showed that adherence to lenses decreased as the time of
      exposure to antimicrobial agents increased. Adherence was greatly diminished with
      cells treated with gentamicin or ciprofloxacin compared with control untreated
      cells. Adherence was less affected by clindamycin, ceftazidime and vancomycin.
      The data supported the use of antimicrobial agents in irrigating solution during
      intraocular surgery, since, reduced adherence (colonization) and might result in
      a lower incidence of endophthalmitis.

PMID- 11463528
TI  - Methicillin-resistant Staphylococcus aureus in the hospitals of central Greece.
AB  - A total of 250 consecutive Staphylococcus aureus clinical isolates were collected
      during the period 1999-2000 from the five major hospitals of the district of
      Thessaly (Central Greece). Thirty seven (14.8%) of the isolates were mecA
      positive (MRSA) in a PCR-based assay; all exhibited resistance to oxacillin (agar
      dilution MICs > or =4 mg/L) and were also resistant to multiple antibiotics. Most
      of the MRSA isolates had been collected in the intensive care units and the
      surgical wards of the participating hospitals in a sporadic fashion. The MRSA
      incidence found here was significantly lower than reported in previous studies
      from Greece. Molecular typing by PFGE showed that the MRSA isolates were
      distributed between three pulsotypes. Evaluation of various conventional methods
      for assessing methicillin resistance showed that oxacillin agar dilution and
      immunological detection of PBP2a with the Slidex MRSA Detection kit were the most
      reliable in this setting. Misclassifications of isolates exhibiting low-level
      resistance (oxacillin MIC 2-4 mg/L) occurred with the salt agar screen, the
      oxacillin disk diffusion and the ATB Staph System methods.

PMID- 11463529
TI  - Combination of benzo[a]phenothiazines with acyclovir against herpes simplex
      virus.
AB  - The combined antiviral effects of some benzo[a]phenothiazines and 9-[2
      hydroxy(ethoxy)methyl]guanine (acycloguanosine, acyclovir, ACV) on the
      multiplication of herpes simplex virus type 2 (HSV-2) were studied using Vero
      cells. The antiviral effect of ACV on a wild strain of HSV-2 was enhanced in the
      presence of 5-oxo-5H-benzo[a]phenothiazine and 6-methyl-5-oxo-5H
      benzo[a]phenothiazine in a yield reduction test. A mathematical formula was used
      to interpret the drug interaction and a synergistic effect was found with a
      combination of ACV and benzo[a]phenothiazines. The effect of simultaneous
      application of two benzo[a]phenothiazines on the multiplication of HSV-2 strain
      during serial passages was also investigated. The combinations of 5-oxo-5H
      benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine with ACV at a
      low concentration using serial passages of a plaque-purified ACV sensitive HSV-2
      strain, reduced the infective virus population. A similar effect was also found
      on the activity of other benzo[a]phenothiazine derivatives. When the two most
      effective derivatives of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H
      benzo[a]phenothiazine were simultaneously used with ACV against a wild type HSV-2
      strain during consecutive passages, the infective virus titres were decreased,
      but their effect was only moderate. These results suggest that a combination of
      some benzo[a]phenothiazines with ACV might enhance their antiviral activity
      probably by reduction of the mutagenic rate in the virus populations.

PMID- 11463530
TI  - Activity of the ketolide telithromycin (HMR-3647) against erythromycin
      susceptible and -resistant pneumococci isolated in the UK.
AB  - The novel ketolide telithromycin (formerly HMR-3647) was tested against a
      collection of pneumococci of varying sensitivity to erythromycin and clindamycin,
      isolated in geographically diverse UK hospitals. Telithromycin was highly active
      against erythromycin-susceptible pneumococci, the MIC(90) being 0.015 mg/l.
      Erythromycin-resistant pneumococci that contained the ermB gene, either alone or
      together with the mefE gene, were cross-resistant to other macrolides and to
      clindamycin, while erythromycin-resistant pneumococci that contained only the
      mefE gene were cross-resistant to azithromycin, clarithromycin and roxithromycin
      but remained susceptible to josamycin and clindamycin. Telithromycin was active
      against erythromycin-resistant pneumococci irrespective of their mechanism of
      macrolide resistance, although the MIC(90) (0.25 mg/l) was higher than that seen
      with erythromycin-sensitive isolates. Telithromycin thus appears to be a
      potentially useful drug in settings where pneumococcal resistance to macrolides
      is prevalent.

PMID- 11463531
TI  - Activity of gatifloxacin against strains resistant to ofloxacin and ciprofloxacin
      and its ability to select for less susceptible bacterial variants.
AB  - Gatifloxacin is an 8-methoxy fluoroquinolone. On quinolones, this side chain
      imparts increased activity against Gram-positive bacteria and enhanced killing.
      Gatifloxacin was tested against ofloxacin non-susceptible (ofloxacin MIC>2 mg/l)
      strains of Streptococcus pneumoniae (gatifloxacin MIC(90), 1 mg/l) and
      methicillin-resistant Staphylococcus aureus (MRSA, gatifloxacin MIC(90), 4 mg/l),
      and to ciprofloxacin non-susceptible (ciprofloxacin MIC>1 mg/l) strains of
      Escherichia coli (gatifloxacin MIC(90),>16 mg/l) and ciprofloxacin non
      susceptible (ciprofloxacin MIC>0.06 mg/l) Neisseria gonorrhoeae (gatifloxacin
      MIC(50), 0.12 mg/l and MIC(90), 0.5 mg/l). Though gatifloxacin showed some
      reduced susceptibility to these populations, the MIC(50) and MIC(90) values
      suggest that gatifloxacin may be useful against pneumococci and some gonococcal
      strains not susceptible to other fluoroquinolones. Gatifloxacin did not select
      for less susceptible variants of MRSA and pneumococci, in contrast to the 10- to
      100-fold higher selection frequencies with ciprofloxacin and ofloxacin. The
      single-step E. coli mutants selected by gatifloxacin and the comparator
      quinolones had quinolone MICs within the susceptible range. These data suggest
      that gatifloxacin use may hinder the development of quinolone-resistance,
      particularly in Gram-positive bacteria.

PMID- 11463532
TI  - Identity and antibiotic susceptibility of enterobacterial flora of salad
      vegetables.
AB  - The enterobacterial flora from carrots (organic and non-organic) and salad
      vegetables has been identified and antibiotic susceptibilities determined.
      Pseudomonas fluorescens and Pantoea (formerly Enterobacter) agglomerans were the
      species most commonly found; the former was usually resistant to at least six of
      the antibiotics under test. Rahnella aquatilis (often producing beta-lactamase)
      was also found in carrots. There were no clear differences in flora from organic
      and non-organic carrots. Thus, uncooked vegetables are a potential source of
      highly resistant opportunistic pathogens.

PMID- 11463533
TI  - Antibacterial activity of black myrobalan (Terminalia chebula Retz) against
      Helicobacter pylori.
AB  - The effect of ether, alcoholic and water extracts of black myrobalan (Teminalia
      chebula Retz) on Helicobactor pylori were examined using an agar diffusion method
      on Columbia Agar. Water extracts of black myrobalan showed significant
      antibacterial activity and had a minimum inhibitory concentration (MIC) and
      minimum bacteriocidal concentration (MBC) of 125 and 150 mg/l, respectively. The
      extract was active after autoclaving for 30 min at 121 degrees C. Plant powder
      (incorporated in agar) gave higher MIC and MBC values (150 and 175 mg/l,
      respectively). Water extracts of the black myrobalan at a concentration of 1-2.5
      mg/ml inhibited urease activity of H. pylori. The results show that black
      myrobalan extracts contain a heat stable agent(s) with possible therapeutic
      potential. Other bacterial species were also inhibited by black myrobalan water
      extracts.

PMID- 11463534
TI  - Effect of cyclosporin on uropathogenic Escherichia coli adherence to human
      endothelial cells.
AB  - The effect of cyclosporin A on the adherence of Escherichia coli strains to human
      umbilical vein endothelial cells was studied. Compared with the controls,
      bacterial adherence significantly increased following preincubation of the cells
      with cyclosporin A at 50 mg/l and more significantly, to cells preincubated with
      cyclosporin A at 100-200 mg/l. The results showed that cyclosporin A use may be
      accompanied by an increased bacterial adherence to host cells in vivo. This
      effect was achieved using a wide range of therapeutic doses.

PMID- 11463535
TI  - Truncus arteriosus repair: outcomes, risk factors, reoperation and management.
AB  - OBJECTIVES: Truncus arteriosus (TA) continues to be associated with significant
      morbidity and mortality, but there have been clinically significant improvements
      with early repair. METHODS: Sixty patients underwent physiological correction of
      TA between November 1978 and January 2000. The average age was 76 days (range, 3
      days--20 months). Associated cardiac anomalies were frequently encountered, the
      most common being severe truncal valve regurgitation (n=7), interrupted aortic
      arch (n=6), coronary artery anomalies (n=6), non-confluent pulmonary arteries
      (n=4), and total anomalous pulmonary venous return (n=1). Truncal valve
      replacement was performed initially or subsequently in seven patients with severe
      regurgitation (mechanical prostheses in six patients and a cryopreserved aortic
      homograft in one patient). Right ventricle--pulmonary artery continuity was
      established with an aortic (n=16) or pulmonary homograft (n=32) in 48 patients, a
      Dacron polyester porcine valved conduit in five, a non-valved
      polytetrafluoroethylene (PTFE) tube in three, direct anastomosis to the right
      ventricle with anterior patch arterioplasty in three, and a bovine jugular venous
      valve conduit in one patient. RESULTS: There were ten hospital deaths (17%; 70%
      confidence limit, 7--25%). Multivariate and univariate analyses demonstrated a
      relationship between hospital mortality and associated cardiac anomalies. In the
      43 patients without these associated cardiac anomalies, the early survival was
      91% (group I). In the 17 patients with one or more of these risk factors, the
      survival was 71% (group II, P=0.002). There was one late death. Twenty-three
      patients (46%) required reoperation for right ventricular outflow tract (RVOT)
      obstruction at a mean follow-up time of 59.1 months. In 23 patients, the RVOT
      reconstruction was performed with a PTFE monocusp, and six patients had of a
      variety of replacement conduits inserted. Postoperatively, there were 34 (68%)
      patients in New York Heart Association functional class I and 16 (32%) in class
      II. Twenty-eight surviving patients are reported as doing well without any
      medication. The freedom of reoperation in the 39 hospital survivors (group I)
      without risk factors was 64% at 7 years; and 36% at 10 years in the 11 patients
      (group II) surviving with risk factors. CONCLUSIONS: Associated cardiac anomalies
      were risk factors for death after the repair of TA. In the absence of these
      associated lesions, TA can be repaired with an excellent surgical outcome in the
      neonatal and early infancy period.

PMID- 11463536
TI  - Double inlet right ventricle versus other types of double or common inlet
      ventricle: its clinical characteristics with reference to the Fontan procedure.
AB  - OBJECTIVE: To determine the clinical features in patients with double inlet right
      ventricle (DIRV) and separate atrioventricular (AV) valves in terms of the Fontan
      procedure. METHODS: Surgical procedures were carried out in 31 patients with this
      rare malformation. Their clinical characteristics were compared with similar
      features in 45 patients with double inlet left ventricle (DILV), 93 with common
      inlet right ventricle (CIRV), and 20 with common inlet left ventricle (CILV).
      RESULTS: Pulmonary atresia with the right and the left pulmonary arteries being
      confluent was seen in 58% of patients with DIRV, and pulmonary atresia with non
      confluent pulmonary arteries in 15% (P=0.0001). The incidence of these findings
      was significantly higher when compared with DILV (P=0.0001). Reflecting these
      morphologic features, constructions of systemic-to-pulmonary shunts and extensive
      plasty to the pulmonary arteries were more frequently needed in patients with
      DIRV than in the others (P=0.04, 0.0001). The AV valves have become moderately or
      severely regurgitant in three with DIRV (10%). The Fontan procedure has thus been
      employed in 21 with DIRV (64%), this incidence being significantly higher than
      that seen in the CIRV (37%) group (P=0.01). Survival rate of 95% at 10 years in
      this group was as excellent as that in the DILV group, and obviously better than
      that in either CIRV or CILV (P=0.002). CONCLUSIONS: Although multiple palliative
      procedures might be frequently needed to maintain pulmonary perfusion, the Fontan
      circulation can be justifiably established in patients with DIRV, and
      regurgitation across the AV valves was not very common.

PMID- 11463537
TI  - Usefulness of vacuum-assisted cardiopulmonary bypass circuit for pediatric open
      heart surgery in reducing homologous blood transfusion.
AB  - OBJECTIVE: Open-heart surgery without homologous blood transfusion is still
      difficult in children because priming volume in cardiopulmonary bypass circuit
      results in extreme hemodilution. Vacuum-assisted cardiopulmonary bypass circuit
      has the benefit of improving venous return and results in lowering priming
      volume. We introduced vacuum-assisted cardiopulmonary bypass circuit in order to
      reduce priming volume for pediatric patients in March 1995. A retrospective study
      was made on the efficacy of vacuum-assisted circuit for pediatric open-heart
      surgery in reducing homologous blood transfusion. METHODS: Patients weighing from
      5 to 20 kg who underwent surgery between January 1991 and June 1996 were divided
      into two groups, group A comprised 128 patients before introduction of this
      circuit and group B comprised 49 patients after introduction, and their clinical
      course was compared. Vacuum-assisted circuit was used in 27 patients of group B.
      RESULTS: The percentage of transfusion-free operations was significantly higher
      in group B than in group A (33.6% in group A vs. 53.1% in group B, P = 0.014),
      and particularly this percentage in patients weighing less than 10 kg
      significantly increased (0% in group A vs. 42.9% in group B, P < 0.01). The
      amount of homologous blood transfusion was significantly lower in group B than in
      group A (374 +/- 362 ml in group A and 212 +/- 287 ml in group B, P < 0.01). The
      rate of complications and the duration of respiratory support did not differ
      between the two groups. The duration of hospital stay was lower in group B than
      in group A. CONCLUSIONS: The findings of this study indicate that vacuum-assisted
      circuit is useful for pediatric open-heart surgery in reducing homologous blood
      transfusion.

PMID- 11463538
TI  - Is there still a place for open surgical valvotomy in the management of aortic
      stenosis in children? The view from Southampton.
AB  - OBJECTIVE: The most appropriate management of aortic stenosis (AS) in children
      remains controversial. The purpose of this study was to determine the outcome
      following open valvotomy for AS in children. METHODS: Ninety-seven consecutive,
      unselected, children (mean age 3.2 +/- 3.6 years, 1 day--15 years) underwent an
      open valvotomy for critical (n=36) or severe (n=61) AS between 1979 and 2000 in
      Southampton. Twenty-six were neonates (1--31 days), 27 were infants (1--12
      months) and 44 were older children (1--15 years). Mean follow-up was 10 +/- 5.4
      years, 1 month--21.9 years. RESULTS: Two neonates died early giving an overall
      operative mortality of 2.1% (7.7% for the neonates and 0% for infants and older
      children). The mean aortic gradient was reduced from 76 to 24.5 mmHg (P <
      0.0001). Residual or recurrent AS occurred in 17 patients and severe aortic
      regurgitation in eight patients. Kaplan--Meier 10-year freedom from residual or
      recurrent AS was 83.1 +/- 4.7% and from severe aortic regurgitation was 95.3 +/-
      2.7%. Twenty-five patients required an aortic re-operation or re-intervention, 18
      of whom had an aortic valve replacement (AVR) (mean valve size 21.8 +/- 0.9 mm,
      range 21--25 mm). Ten-year freedom from any aortic re-operation or re
      intervention was 78.4 +/- 5.2% and from AVR was 85.1 +/- 4.6%. There were ten
      late deaths. Overall 10-year survival, including hospital mortality, was 90.2 +/-
      3.1% (69.7 +/- 9.7% for the neonates, 92 +/- 5.4% for the infants and 100% for
      older children, (P < 0.0001). Ten-year survival for children with isolated AS (n
      = 69) was 100% and for those with associated cardiovascular problems (n = 28) was
      67.3 +/- 8.9% (P < 0.0001). All survivors are in New York Heart Association
      functional class I. CONCLUSIONS: Open valvotomy remains the gold standard in the
      management of AS in neonates, infants and older children. It is associated with
      low operative mortality and provides lengthy freedom from recurrent AS and
      regurgitation. Re-operations are common but if AVR is required, implantation of
      an adult-sized prosthesis is usually possible. There is a late death-hazard for
      those with severe associated lesions, but the survival prospects for the patients
      with isolated AS are excellent.

PMID- 11463539
TI  - Repair of moderate aortic valve lesions associated with other pathology: an 11
      year follow-up.
AB  - OBJECTIVES: The presence of moderate aortic valve (AV) lesions associated with
      other pathologies that require surgery presents a problem since ignoring or
      replacing the valve seems unsatisfactory. AV repair can be an attractive
      alternative if shown to perform satisfactory. METHODS: To evaluate this
      possibility, all consecutive AV patients who underwent operation between July
      1988 and July 1999 were reviewed. Out of 1764 AV patients, 239 (14%) underwent
      repair and 86 (study group) had moderate lesions associated with mitral (73),
      tricuspid (33), coronary disease (5) and others (8). Mean age was 28 years (range
      2--66); 78% were rheumatic, 71% were in sinus rhythm and 71% in NYHA class III-
      IV. RESULTS: There were seven hospital deaths (8%) and three patients were lost
      to follow-up (95% complete). Late mortality was 8% and 10-year actuarial survival
      was 86 +/- 4.5% (excluding hospital mortality). There were four (5%) embolic
      events (actuarial freedom 94 +/- 3.5%). Twenty-one patients required reoperation
      with two mortalities. The AV was not touched in five patients. In the remaining
      16, the AV was replaced. Only one patient had isolated AV replacement while in
      all others, additionally, the mitral, tricuspid, or both required surgery. All
      reoperated patients had rheumatic etiology. Actuarial freedom from AV dysfunction
      at 8 years was 68 +/- 7.5%. CONCLUSIONS: Repair of associated moderate AV lesion
      is worth considering even in a predominantly young rheumatic population.

PMID- 11463540
TI  - Composite stentless valve with graft extension for combined replacement of the
      aortic valve, root and ascending aorta.
AB  - OBJECTIVE: The composite mechanical valve conduit has been most commonly used for
      patients who require combined aortic valve, root, and ascending aorta
      replacement, but is limited, especially in the elderly, because of the need for
      long-term anticoagulation. We report the first consecutive series of patients in
      whom a composite stentless valve with graft extension, which does not require
      long-term anticoagulation, was performed. METHODS: Between April 1998 and July
      2000, eight patients with severe aortic root and ascending aortic pathology
      underwent a combined aortic valve, root, and ascending aorta replacement with a
      Freestyle stentless porcine valve with a Hemashield graft extension. Mean age was
      74 (range 56--82), three were males. Concomitant procedures included coronary
      artery bypass graft (CABG) alone (n=2), mitral valve replacement with atrial
      septal defect repair (n=1) and CABG with septal myomectomy (n=1). RESULTS:
      Operative mortality was zero. Median aortic cross-clamp and cardiopulmonary
      bypass times were 150 and 203 min, respectively. Two patients returned to the
      operating room for bleeding. Median blood transfusions and hospital length of
      stay were 4 units and 11 days, respectively. CONCLUSIONS: The composite stentless
      valve with graft extension is a reasonable alternative to a mechanical valve
      conduit for patients who require a combined aortic valve, root, and ascending
      aorta replacement, in whom anticoagulation is not desirable or contraindicated.

PMID- 11463541
TI  - Use of the pulmonary autograft for mitral replacement: short- and medium-term
      experience.
AB  - OBJECTIVES: In an effort to find a suitable mitral substitute for our young
      rheumatic patients who cannot follow a proper anticoagulation regimen for life,
      we resorted to an old concept reported by one of the authors (D.N.R.) in 1967.
      This report summarizes our experience with the Ross-mitral operation to date.
      METHODS: Between 19 June 1997 and 27 June 2000, 43 patients with rheumatic valve
      disease underwent the Ross-mitral operation. Two patients were excluded because
      of graft stenosis detected at the end of the procedure for which the autograft
      had to be sacrificed. Of the remaining 41 patients 29 were female, and the age
      range was 12--57 years (median 39 years). The autograft was incorporated within a
      Dacron tubing, with a pericardial collar attached to its proximal end. The
      conduit was sutured distally to the excised mitral annulus; the pericardium was
      attached proximally to the atrial wall in 36 patients, and was used simply to
      cover the Dacron tubing in five patients. The pulmonary artery was replaced with
      a pulmonary or aortic homograft, or with a pulmonary xenograft. RESULTS: There
      were two hospital fatalities from a cerebrovascular accident and a lung injury,
      and two postoperative myocardial infarctions. There were five late deaths, two
      due to bacterial endocarditis, one due to excessive bleeding at reoperation for a
      paravalvular leak, and two not related to the procedure. A phenomenon of
      'autograft stenosis' occurred intraoperatively in four recent consecutive
      patients that probably resulted from our use, for the first time, of softer
      Dacron tubing material. This was repaired in two of the four patients.
      Echocardiography confirmed excellent functioning of all 34 autografts of
      surviving patients up to 36 months postoperatively (mean follow-up 18.2 months).
      Two patients remain in functional Class III status, one due to left heart failure
      following myocardial infarction, and the other due to recurrent tricuspid
      insufficiency. CONCLUSIONS: We believe that the mitral pulmonary autograft is a
      worthwhile alternative to mechanical prostheses in developing countries.

PMID- 11463542
TI  - Preliminary observations on haemodynamics during physiological stress conditions
      following 'double-orifice' mitral valve repair.
AB  - OBJECTIVE: The 'double-orifice' (DO) technique has been proposed to simplify
      mitral valve repair (MVRep) in particular settings of mitral insufficiency.
      However, the haemodynamic effects of such a redesigned valve are poorly
      documented, particularly during stress conditions. Thus, we sought to evaluate
      the haemodynamic changes during exercise conditions after the DO procedure.
      METHODS: Twenty-seven selected patients were enrolled for this study. Mean age
      was 60 +/- 14 years (range 31--80 years). All patients had had severe mitral
      regurgitation and normal LV function preoperatively, and had undergone DO as
      isolated procedure for MVRep. Annular remodelling was associated in 24 cases
      (Carpentier classic ring in 13 patients and autologous pericardium in 11
      patients, respectively). Postoperatively, haemodynamic data were recorded at
      baseline and during supine exercise test at submaximal workloads by means of
      transthoracic echocardiography. A logistic regression analysis was applied to
      evaluate the association between the observed haemodynamic changes and surgical
      technique. RESULTS: Mean follow-up was 47 +/- 20 months. Significant residual
      mitral insufficiency (grade three over four) was found in five patients at
      baseline assessment, and in six patients at peak exercise. Transmitral pressure
      gradient showed a significant (P < 0.001) increase in both peak and mean values
      at peak exercise (from 7 +/- 4 to 17 +/- 10 and from 3 +/- 2 to 8 +/- 6 mmHg,
      respectively). Pulmonary hypertension was observed in six patients (moderate in
      all cases) at rest and in 13 patients (moderate in seven cases and severe in five
      cases) at peak exercise. We did not find any correlation between the haemodynamic
      data and surgical factors. CONCLUSIONS: This study indicates that though
      effective mitral valve competence is achieved in the majority of operated
      patients, DO repair may induce impaired diastolic mitral dynamism in some cases,
      particularly during exercise conditions. Further investigations are required to
      thoroughly elucidate the overall mechanics of a DO valve, especially at strenuous
      cardiocirculatory states.

PMID- 11463543
TI  - Combined mitral valve and coronary artery surgery: ischemic versus non-ischemic
      mitral valve disease.
AB  - OBJECTIVES: Mitral valve combined with coronary artery surgery is associated with
      a higher hospital mortality than each operation in particular. Controversy exists
      regarding the predictive value of ischemic mitral valve disease (MVD) on outcome.
      METHODS: Between 1984 and 1997, 262 patients underwent mitral valve operations
      (replacement, n = 198; repair, n = 64) in combination with coronary
      revascularization. The etiology of MVD was secondary to ischemic heart disease
      (group I) in 82 (31%) patients, and non-ischemic (group II) in 180 (69%) patients
      (rheumatic, 139 patients (53%); degenerative, 41 patients (16%)). Both groups
      were similar in age, cardiac risk factors and pulmonary artery pressure. Patients
      of group I had significantly more severe coronary artery disease, more often an
      impaired left ventricle and myocardial infarction, and were in a worse functional
      condition. The mean number of bypass grafts was significantly higher in group I.
      The follow-up was 98% (230/234 patients). RESULTS: With 19.5%, the hospital
      mortality was significantly increased in group I compared with 6.7% in group II
      (P = 0.002; overall, 10.7%). Mitral valve repair or replacement had no influence
      on early outcome, although mitral valve repair was performed more often in group
      I (37 versus 19%). The survival (valve-related event-free survival) after
      discharge from hospital in the 1st, 5th and 10th year was 94 (94%), 70 (66%) and
      53% (35%) in group I and 96 (95%), 79 (76%) and 54% (41%) in group II,
      respectively. The long-term functional capacity was equally good in both groups
      (New York Heart Association mean, 1.86 versus 1.72). CONCLUSIONS: Patients with
      ischemic MVD are in a worse cardiac condition with significantly higher hospital
      mortality than patients with non-ischemic MVD and coronary artery bypass
      grafting. Once discharged from hospital, both groups have comparable long-term
      outcomes, with the best results in patients with degenerative MVD.

PMID- 11463544
TI  - The importance of grade 2 ischemic mitral regurgitation in coronary artery bypass
      grafting.
AB  - OBJECTIVE: To study if grade 2 ischemic mitral regurgitation (MR) influences
      outcome after coronary artery bypass grafting (CABG). METHODS: Results of all
      CABG patients with grade 2/4 ischemic MR operated during 1995--1998 (n = 89) were
      compared with all CABG patients without MR (n = 4709) during the same period. To
      further evaluate patients with grade 2 ischemic MR, a case-control study focusing
      on functional status was performed. Control patients without MR (n = 89) were
      matched for age, gender and left ventricular ejection fraction. All patients were
      interviewed regarding angina symptoms and functional status. RESULTS: Survival
      according to Kaplan--Meier at 1 and 3 years were inferior in the MR group
      compared to all CABG patients (91 vs 96% and 84 vs 92%, respectively (P =
      0.0017). However, MR patients were older (68 +/- 9 vs 65 +/- 9 years (mean +/-
      SD), P = 0.008) and had an inferior preoperative left ventricular ejection
      fraction (42 +/- 14 vs 58 +/- 14%, P < 0.0001). In the case-control study, New
      York Heart Association (NYHA) class and Higgins' risk score differed
      preoperatively between the MR group and controls. Neither 30-day mortality (4,5%
      in both groups) nor survival at 1 (91 vs 93%) and 3 years (84 vs 88%) differed
      significantly. NYHA class and angina class (Canadian Cardiovascular Society, CCS)
      improved similarly in both groups. Postoperatively, 62% of the patients in the MR
      group had reduced, 36% unchanged and 2% increased MR. CONCLUSIONS: CABG on
      patients with grade 2 ischemic MR reduces angina pectoris and improves functional
      status to the same extent as in CABG patients without MR. Postoperative morbidity
      and mortality do not differ significantly between the groups. Grade of MR is
      reduced or unchanged after CABG in patients with grade 2 ischemic MR. The study
      supports an operative strategy where grade 2 ischemic mitral regurgitation is
      treated by CABG alone but the result do not exclude that there might be
      individual patients that would benefit from a valvular or annular procedure in
      combination with CABG. How these patients should be identified remains unclear.

PMID- 11463545
TI  - Does a hyperoncotic cardiopulmonary bypass prime affect extravascular lung water
      and cardiopulmonary function in patients undergoing coronary artery bypass
      surgery?
AB  - OBJECTIVE: Different types of colloidal priming for cardiopulmonary bypass (CPB)
      have been used to reduce fluid load and to avoid the fall of plasma colloid
      osmotic pressure (COP) that leads to edema formation and consequently can cause
      organ dysfunction. The discussion about the optimal priming composition, however,
      is still controversial. We investigated the effect of a hyperoncotic CPB-prime
      with hydroxyethyl starch (HES) 10% (200;0.5) on extravascular lung water (EVLW)
      and post-pump cardiac and pulmonary functions. METHODS: In 20 randomized patients
      undergoing elective coronary artery bypass graft surgery (CABG), a colloid prime
      (COP: 48 mmHg, HES-group, n = 10) and a crystalloid prime (Ringer's lactate,
      crystalloid group, n = 10) of equal volume were compared with respect to the
      effects on cardiopulmonary function. Cardiac index (CI), mean arterial pressure
      (MAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance
      index (SVRI), pulmonary artery pressure (PAP), pulmonary vascular resistance
      index (PVRI), alveolo-arterial oxygen difference (AaDO(2)), pulmonary shunt
      fraction (Q(s)/Q(T)), EVLW (double-indicator dilution technique with ice-cold
      indocyanine green), COP, fluid balance and body weight were evaluated peri
      operatively. RESULTS: Pre-operative demographic and clinical data, CPB-time,
      cross-clamp time and the number of anastomoses were comparable for both groups.
      During CPB, COP was reduced by 20% in the HES-group (18.9 +/- 3.7 vs. 23.7 +/-
      2.2 mmHg, P < 0.05) while it was reduced by more than 50% of the pre-CPB value
      (9.8 +/- 2.0 vs. 21.4 +/- 2.1 mmHg, P < 0.05) in the crystalloid group (P < 0.05
      HES- vs. crystalloid group). Post-CPB EVLW was unchanged in the HES-group but it
      was elevated by 22% in the crystalloid group (P < 0.05 HES- vs. crystalloid
      group), CI was higher in the HES-group (3.4 +/- 0.3 vs. 2.7 +/- 0.5l/min, P <
      0.05). Fluid balance was less in the HES-group (813 +/- 619 vs. 2143 +/- 538, P <
      0.05). Post-operative weight gain could be prevented in the HES-group but not in
      the crystalloid group (1.5 +/- 1.2 vs. -0.3 +/- 1.5, P < 0.05). No significant
      differences were seen for MAP, PAP, PCWP, SVRI, PVRI, AaDO(2) and (Q(s)/Q(T))
      between the two groups at any time. CONCLUSIONS: Hyperoncotic CPB-prime using HES
      10% improves CI and prevents EVLW accumulation in the early post-pump period,
      while pulmonary function is unchanged. This effect can be of benefit especially
      in patients with congestive heart failure.

PMID- 11463546
TI  - Ischemically compromised myocardium displays different time-courses of functional
      recovery: correlation with morphological alterations?
AB  - OBJECTIVE: It has been demonstrated that positron emission tomography (PET)
      predicts the functional recovery of viable but ischemically compromised
      myocardium. Reversible contractile dysfunction after revascularization has been
      reported for 'hibernating myocardium' and stunned myocardium, however, there are
      little data concerning the time-course and the extent of improvement of the two
      different pathophysiological conditions. METHODS: Twenty-nine patients with
      advanced coronary artery disease and severely reduced left ventricular function
      (EF 18--35%) who were referred for isolated coronary artery bypass grafting
      underwent preoperative PET viability assessment and were functionally assessed by
      two-dimensional echocardiography preoperatively at 11 days, 14 weeks, and more
      than 12 months after surgical revascularization. Intraoperative biopsies were
      taken from dysfunctional areas defined by PET as segments of normal perfusion and
      normal metabolism (stunned myocardium) and from areas with a 'mismatch' between
      perfusion and metabolism (hibernating myocardium). The degree of morphological
      alterations was evaluated by electron microscopy. RESULTS: In 70% of the 240
      dysfunctional segments, 'stunned myocardium' was present whereas 'hibernating
      myocardium' could be detected in only 24% (P < 0.01). Hibernating myocardium was
      associated with more severe preoperative wall motion abnormalities and incomplete
      postoperative recovery. After 1 year, 31% of 'stunned' segments vs. only 18% of
      'hibernating' segments showed complete functional restoration (P < 0.05). This
      incomplete improvement was associated with more severe morphological alterations
      including depletion of sarcomeres, accumulation of glycogen, loss of
      sarcoplasmatic reticulum, and cellular sequestration. CONCLUSIONS: These data
      indicate that in patients with severe ischemic left ventricular dysfunction
      'stunned myocardium' is more prevalent than 'hibernation'. Functional
      normalization is more frequent in 'stunned' segments, whereas areas of
      'hibernation' showed more severe tissue injury and protracted recovery. Different
      degrees of myocardial injury coexist in most patients, which determines the time
      course and the extent of improvement after revascularization.

PMID- 11463547
TI  - Composite arterial grafting with double skeletonized internal thoracic arteries.
AB  - OBJECTIVES: Composite arterial grafting is a surgical technique for arterial
      myocardial revascularization, in which free arterial conduits are proximally
      anastomosed end-to-side to an intact internal thoracic artery (ITA). This report
      describes technical aspects and results of composite grafting using bilateral
      skeletonized ITAs. METHODS: From April 1996 to February 1999, 1057 patients
      underwent coronary artery bypass grafting (CABG) using bilateral skeletonized
      internal thoracic arteries. In 600 of them (57%), composite arterial grafting was
      performed. There were 452 men and 148 women. The mean age was 69 +/- 7 years. Two
      hundred and six patients (34%) were diabetics, 84 (14%) had severe left
      ventricular dysfunction (ejection fraction of < 35%), and 26 (4.3%) underwent
      emergency operations. In 574 patients, the right ITA was used as a free graft
      connected to the in-situ left ITA. In 26, the free left ITA was attached to the
      in-situ right ITA, and in 38, mini-composite grafts (free distal left ITA on the
      left ITA, or free distal right ITA on the right ITA) were constructed. The
      average number of grafts was 3.0/patient (range, 2--6). RESULTS: The operative
      mortality was 2.8% (n = 17), and there were ten (1.7%), deep sternal wound
      infections. The mean follow-up was 25 months (range, 14--36 months). The 3-year
      survival was 92.5%. Ninety-seven percent of the surviving patients were angina
      free. CONCLUSIONS: We currently perform this surgery routinely in most patients
      referred for CABG, and regard bilateral skeletonized internal thoracic arteries
      as the most appropriate arterial conduits for the composite technique.

PMID- 11463548
TI  - Vasoreactivity of arterial grafts in the patient with diabetes mellitus:
      investigations on internal thoracic artery and radial artery conduits.
AB  - OBJECTIVE: Arterial revascularization with either internal thoracic artery (ITA)
      or radial artery (RA) appears to be particularly attractive in diabetic patients.
      Previous investigations have shown that endothelial dysfunction and
      artherosclerosis are seen more often in these patients. The aim of this study was
      to compare the vasoreactive properties of ITA and RA grafts in diabetic and non
      diabetic patients. METHODS: Arterial rings were harvested from 57 patients who
      underwent complete arterial revascularization. The patients were divided into a
      non-diabetic group (I: n = 30) and patients with diabetes mellitus (II: n = 27).
      Arterial rings of the ITA (I: n = 30; II: n = 27) and RA (I: n = 28; II: n = 19)
      were mounted on a strain gauge in oxygenated, normothermic Krebs's--Henseleit
      solution at optimal resting tension. With KCL (80 mM) serving as the control,
      assessment of force of contraction (norepinephrine), endothelium-dependent
      relaxation (acetylcholine) and smooth muscle-dependent relaxation
      (glyceroltrinitrate) were obtained. RESULTS: After KCL, the RA showed a trend to
      lower maximum contraction forces in diabetics (I: 76 +/- 25 mN; II: 69 +/- 29
      mN), which was pronounced in patients with diabetes of more than 10 years
      duration (55 +/- 23 mN; P = 0.1). Maximum contraction force of the ITA was
      similar in both groups (I: 41 +/- 20 mN; II: 34 +/- 19 mN) and not influenced by
      the duration of diabetes. The two groups showed no significant differences of the
      relative vasoconstriction after norepinephrine in RA (I: 53 +/- 18%; II: 61 +/-
      19%) and ITA rings (I: 70 +/- 23%; II: 69 +/- 25%). Also, endothelium-dependent
      relaxation with acetylcholine in RA (I: 53 +/- 14%; II: 57 +/- 16%) and ITA rings
      (I: 42 +/- 17%; II: 44 +/- 20%), and smooth muscle relaxation with
      glyceroltrinitrate of RA (I: 72 +/- 8%; II: 73 +/- 12%) and ITA rings (I: 64 +/-
      12%; II: 58 +/- 20%) was comparable in both groups. No influence of duration of
      the diabetic disease was noted. CONCLUSIONS: Although RA rings of patients with a
      long duration of diabetes have decreased maximum contraction forces, their
      relative vasoconstriction after norepinephrine, endothelium-dependent relaxation
      and smooth muscle relaxation was similar to non-diabetic patients. We thus
      conclude that the RA is an adequate arterial conduit in the patient with diabetes
      mellitus.

PMID- 11463549
TI  - A UK trial-based cost--utility analysis of transmyocardial laser
      revascularization compared to continued medical therapy for treatment of
      refractory angina pectoris.
AB  - OBJECTIVE: Transmyocardial laser revascularization (TMLR) is used to treat
      patients with refractory angina considered unsuitable for conventional forms of
      revascularization. Using patient specific data from a single centre UK randomised
      controlled trial, we aimed to determine whether, from a UK National Health
      Service (NHS) perspective, TMLR plus standard medical management is cost
      effective when compared with standard medical management alone. METHODS: One
      hundred and eighty-eight patients assessed as having refractory angina, and not
      suitable for conventional forms of revascularization were randomized to receive
      TMLR and medical management (94) or medical management alone (94). Costs to the
      UK NHS of TMLR (where appropriate), and all secondary sector health care contacts
      and cardiac-related medication in the 12 months following randomization, were
      collected. Patient utility as measured using the EuroQol EQ-5D questionnaire was
      combined with 12-month survival data to generate quality adjusted life years
      (QALYs). RESULTS: The mean cost per patient over the year from hospitalization
      for TMLR was 11,470 pounds sterling and for medical management alone was 2586
      pounds sterling, giving a cost difference of 8901 pounds sterling (95% confidence
      interval (CI) 7502 pounds sterling--10,008 pounds sterling: P < 0.0001). The mean
      QALY difference, in favour of TMLR was 0.039 (95% CI -0.033 to 0.113: P = 0.268).
      This gives an incremental cost per QALY of over 228,000 pounds sterling. Analysis
      of stochastic uncertainty and of sensitivity to gross changes in key parameters
      consistently produces very high costs per QALY. CONCLUSIONS: The policy
      implications are clear: for such patients TMLR is an inefficient use of UK health
      service resources. This conclusion would not be changed by considerable
      improvements in effectiveness or reductions in cost.

PMID- 11463550
TI  - Left ventriculoplasty for ischemic cardiomyopathy.
AB  - OBJECTIVE: In order to treat ischemic cardiomyopathy, which is defined as non
      aneurysmal diffuse akinetic left ventricle with chronic heart failure following
      myocardial infarction, the mid-term effect of the endoventricular circular patch
      plasty (EVCPP) was studied. MATERIALS AND METHODS: EVCPP has been performed on 54
      patients (46 men and eight women with a mean age of 61 years) during 4 years from
      March 1997 to December 2000. Thirty-two patients (59%) were NYHA class III and 22
      patients (41%) were class IV. Nine patients (17%) had mild angina pectoris before
      the operation but others had no chest pain. Single, double, triple, and left main
      disease were noted in six, 13, 32, and three patients, respectively. Mean left
      ventricular ejection fraction was 23.3 +/- 6.3% (6--30%). Coronary artery bypass
      grafting was concomitantly undergone by 51 patients (94%) and mitral valve
      reconstruction was done on 19 patients (35%). RESULTS: Two patients (3.7%) needed
      an intra-aortic balloon pump to wean from cardiopulmonary bypass. Seven patients
      (12.9%) died in the hospital. Among them, two patients (4.4%) out of 45 patients
      who underwent elective operation died of stroke and heart failure. Five patients
      (55.5%) out of nine patients who required emergency operation died of heart
      failure and multiorgan failure. Late death occurred in six patients (11.1%) due
      to arrhythmia and heart failure in each of three patients. Out of 41 survivors,
      38 patients returned to NYHA class I or II and three patients to class III. Out
      of 50 patients who underwent left ventricular study before and after operation,
      ejection fraction increased from 22.8 +/- 6.6 to 36.2 +/- 8.0% and mean left
      ventricular end-diastolic volume and left ventricular end-systolic volume indices
      reduced from 152.8 +/- 24.6 to 105.0 +/- 36.5 and from 113.6 +/- 45.7 to 66.4 +/-
      28.4 ml/m(2), respectively. Mean pulmonary wedge pressure decreased from 19.1 +/-
      8.8 to 14.9 +/- 6.8 mmHg. One-, 2-, and 3-year actuarial survival rates were
      87.9, 82.7 and 77.2%, respectively. CONCLUSION: Left ventriculoplasty using EVCPP
      is effective to exclude the akinetic LV segment, and left ventricular function
      and clinical status improve in patients with ischemic cardiomyopathy.

PMID- 11463551
TI  - Validation of FDG positron emission tomography for differentiation of unknown
      pulmonary lesions.
AB  - OBJECTIVE: The impact of the (2-(fluorine-18)-fluoro-2-2deoxy-D-glucose)-positron
      emission tomography ((18)F-FDG-PET) for discrimination of pulmonary lesions was
      evaluated in a single centre prospective study. METHODS: In the study, 109
      patients with pulmonary lesions of unknown origin verified by computed tomography
      were enrolled consecutively (April 1999--May 2000). They were subject to (18)F
      FDG-PET diagnostics. (18)F-FDG-PET images were interpreted by two independent
      nuclear medicine physicians who were blinded to the results of other imaging
      procedures. In 87 patients, surgery was applied followed by histological
      investigation, which served as the gold standard. In 22 other patients, extensive
      tumour load or assumed benign dignity of the lesions prevented surgery. RESULTS:
      Overall sensitivity of (18)F-FDG-PET in 87 resected patients was 0.86.
      Differentiation in malignant (n = 69) and benign lesions (n = 18) revealed
      sensitivities of 0.9 and 0.72, respectively. Sensitivity of (18)F-FDG-PET in
      inflammatory lesions was markedly lower (0.43) than in benign tumours (0.91).
      Standard uptake values were significantly increased in malignant tumours compared
      with benign lesions (9.9 and 1.6, respectively; P = 0.035). There was a clear
      correlation of sensitivity with tumour size with a failure rate of 27% in lesions
      < or = 1cm (n = 15), 10% (n = 20) in lesions between 1 and 2 cm and 12% (n = 45)
      above 2 cm. In primary bronchial carcinoma, a clear correlation of sensitivity
      was observed with regard to tumour grading (G1, three out of five; G2, 24 out of
      27; G3, 26 out of 26; and G4, one out of one). Lymph node involvement was
      correctly suggested in 10 out of 19 (52.6%) patients. However, false positive
      lymph node enhancement was indicated in one out of 18 (5.5%) operated patients
      with benign lesions and eight out of 39 (20.5%) with bronchial carcinoma.
      CONCLUSION: (18)F-FDG-PET at present does not serve as the gold standard for
      early detection of small and well-differentiated tumours. However, it contributes
      efficiently to the detection of malignancy in tumours >1cm, which are moderately
      or poorly differentiated. Positive lymph node imaging must not preclude surgery
      but requires histological proof. Discrimination of benign and malignant pulmonary
      tumours by (18)F-FDG-PET appears to be hampered in inflammatory lesions.

PMID- 11463552
TI  - Prognostic significance of pleural lavage cytology after resection for non-small
      cell lung cancer.
AB  - OBJECTIVE: In the staging of lung cancer, pleural effusion that is malignant on
      cytologic examination is regarded as T4 disease, and curative resection cannot be
      performed. We conducted this study to determine whether cancer cells can be
      present in the pleural cavity with no pleural effusion, to investigate the
      factors contributing to that occurrence, and to evaluate its prognostic
      significance. METHODS: Eighty-five patients (77 males, eight females) with a
      median age 60.1-+/--7.9 years (31--74 years) underwent a major lung resection,
      due to lung cancer in our department. From January 1998 to December 1999, 30
      pneumonectomies, seven bilobectomies, 46 lobectomies and two wedge-resections
      were performed. Chest wall resection was performed in four patients. After
      performing a posterolateral thoracotomy and lung resection with extended
      mediastinal lymph node dissection, the pleural cavity was filled with 1 l
      physiologic saline solution (PSS) and the fluid was shaken. The lavage fluid was
      suctioned off (S1). Immediately after the lavage, the pleural cavity was refilled
      with 3 l PSS. The surgeon washed out the pleural cavity by hand for 1 min and the
      fluid was suctioned off. Finally, the pleural cavity was refilled with 1 l PSS
      and a new lavage fluid was suctioned off (S2). A cytologic examination was
      carried out for each sample. RESULTS: The pathology report showed 39
      adenocarcinomas, 33 squamous-cell, two adenosquamous, four large-cell, two
      neuroendocrine and five undifferentiated carcinomas. S1 was positive in eight
      patients (9.4%), while S2 was positive in four patients (4.7%). The correlation
      of positive pleural lavage and infiltrated lymph nodes demonstrated a
      statistically significant relation between presence of N2 disease and positive S2
      sample (P = 0.049). No significant correlation existed between positive lavage
      sample (S1 or S2) and TNM stage, level of T, extent of tumor invasion, kind of
      operation, histological type or differentiation of the cancer (Chi square test).
      The mean follow-up is 11.3 +/- 6.2 months (4--22 months). There are 78 patients
      alive. A significance difference in survival was identified in-patients with
      positive S1 (P = 0.0081), and positive S2 (P = 0.0251) (Kaplan--Meier).
      CONCLUSION: The cytologic results of lavage were positive for malignant cells in
      eight of 85 patients (9.4%). The existence of cancer cells in the pleural cavity
      can be the result of their exfoliation or surgical manipulations. The mechanical
      irrigation subdivides the percentage of positive samples. Our study supports that
      the positive findings on pleural lavage cytology is an essential prognostic
      factor.

PMID- 11463553
TI  - Improved pre-operative mediastinal staging in non-small-cell lung cancer by
      serial sectioning and immunohistochemical staining of lymph-node biopsies.
AB  - OBJECTIVE: Mediastinal staging of non-small-cell lung carcinoma (NSCLC) by
      mediastinoscopy suffers from a low sensitivity, leading to a number of patients
      with unforeseen N2 disease at thoracotomy. This study was undertaken to assess
      whether pre-operative staging could be improved by serial sectioning and
      immunohistochemical staining of mediastinoscopy biopsies. METHODS: In 183
      consecutive patients with NSCLC, a thoracotomy was performed after a thorough
      mediastinal staging by computed tomography scan and cervical mediastinoscopy. In
      158 patients (88%), a mediastinal node dissection was performed, revealing
      unforeseen N2 disease in 24 cases (15%). The preserved mediastinoscopy biopsies
      of these patients were retrospectively serially sectioned and stained with MNF
      116. RESULTS: Metastases could be identified in seven cases (30%), reducing
      unforeseen N2 disease from 15 to 10%. The number of patients who could
      theoretically benefit from neo-adjuvant therapy would have been increased by at
      least 10%. CONCLUSIONS: Pre-operative mediastinal staging can be improved
      considerably by serial sectioning and immunohistochemical staining of
      mediastinoscopic biopsy specimens.

PMID- 11463554
TI  - Is lung cancer surgery justified in patients with direct mediastinal invasion?
AB  - OBJECTIVE: To assess the results of the surgical treatment of patients with stage
      IIIB non-small cell lung carcinoma (NSCLC) invading the mediastinum (T4).
      METHODS: Twenty-nine patients were operated on from 1986 to 1999. Histology was
      squamous cell carcinoma in 17 patients, adenocarcinoma in eight, large cell
      carcinoma in two and neuroendocrinal carcinoma in two. Three patients received a
      preoperative chemotherapy (n = 2) or radiochemotherapy (n = 1). The lung
      resection consisted of a pneumonectomy in 25 patients and a lobectomy in four.
      The procedure was extended to one of the following structures: superior vena cava
      (SVC) (n = 17), aorta (n = 1), left atrium (n = 5) and carina (n = 6). Seventeen
      patients had a postoperative regimen including radiochemotherapy (n = 12),
      radiotherapy (n = 4), or chemotherapy (n = 1). RESULTS: Complete R0 resection was
      achieved in 25 patients, whereas four patients had a microscopically (n = 1) or
      macroscopically (n = 3) residual disease. The operative mortality rate was 7% (n
      = 2). Non-fatal major complications occurred in eight patients (28%). Overall 5
      year survival rate was 28% (median 11 months), including the operative mortality.
      The median survival of the 18 patients with an N0 or N1 disease was 16 months
      whereas the median survival of the 11 patients with an N2 disease was 9 months.
      At completion of the study, 22 patients have died, two postoperatively and 10
      from pulmonary causes without evidence of cancer. CONCLUSIONS: Surgical
      management of T4 NSC lung cancer invading the mediastinum should be considered,
      in the absence of N2 disease, when a complete resection is achievable.

PMID- 11463555
TI  - Risk analysis and long-term survival in patients undergoing resection of T4 lung
      cancer.
AB  - OBJECTIVE: The aim of this study is to identify the risk group of patients with
      T4 lung cancer who could more likely benefit from surgical resection. METHODS:
      Between January 1, 1990, and December 31, 1998, 77 patients underwent pulmonary
      resection for T4 lung cancer: lobectomy (n = 20), bilobectomy (n = 4) and
      pneumonectomy (n = 53). The T4 sites of mediastinal involvement were:
      Intrapericardiac portions of the pulmonary artery (n = 30), left atrium (n = 19),
      aorta (n = 8), superior vena cava (n = 8), carina (n = 7), the esophagus (n = 8)
      and the vertebral body (n = 6). Ten patients had multiple neoplastic nodules in
      the same lobe of the lung. RESULTS: Overall survival rates at 1, 2 and 3 years
      were 46, 31 and 21%, respectively. Factors adversely affecting survival with
      univariate analysis included the localization of tumours in the lower lobe (P =
      0.04) and both the involvement of superior and inferior mediastinal lymph nodes
      (P = 0.03). Multivariate analysis included two factors adversely affecting
      survival: the location of the primary tumour and the nodal stations involved.
      Regression tree analysis classified the patients into low-risk group (primary
      tumour in upper lobe or in main stem bronchus and pN0 or pN1 or superior or
      inferior mediastinal nodes involved), intermediate-risk group (primary tumour in
      upper lobe or in main stem bronchus and both superior and inferior mediastinal
      nodes involved, primary tumour in inferior lobe and pN0 or pN1 or inferior
      mediastinal nodes involved) and high-risk group (primary tumour in inferior lobe
      and both superior and inferior nodes involved). The 3-year survival rates were
      36% for the low-risk group, 4% for the intermediate-risk group and 0% for the
      high-risk group (P = 0.006). CONCLUSIONS: In patients with T4 lung cancer, the
      surgery can justify itself for tumours in the upper lobe or in the main stem
      bronchus and with pN0 or pN1.

PMID- 11463556
TI  - Proximal bronchial extension with special reference to tumor localization in non
      small cell lung cancer.
AB  - OBJECTIVE: Surgery is the optimal treatment in patients with non-small cell lung
      cancer (NSCLC) and tumor-negative bronchial resection margins should be
      maintained for a curative resection. The epidemiology of NSCLC, including the
      aspects of tumor localization, has been changing during the recent decades. The
      aim of this study was to evaluate microscopic proximal bronchial extension with
      special reference to the site of the tumor. METHODS: Surgical specimens of 70
      NSCLC cases were examined histologically for proximal bronchial extension of the
      tumor. The entire bronchial tree with the tumor was extracted from the specimen
      and serially cut at a thickness of 5 mm in the transverse plane of the bronchus.
      Microscopic proximal extension of the tumor was classified as either
      endobronchial or peribronchial. RESULTS: Thirty-three (47.1%) tumors had central
      and 37 (52.9%) had peripheral localization. Among the central and peripheral
      tumors, 10 (30.3%) and seven (18.9%) had microscopic proximal extension,
      respectively. In total, the mean length of proximal extension was 10.94 +/- 7.07
      mm. The mean length of extension for peripheral tumors was 15.71 +/- 8.38 mm,
      significantly greater than that of central tumors, which was 7.60 +/- 3.47 mm (P
      = 0.026). Peripheral tumors showed a significant peribronchial extension (P =
      0.024). CONCLUSIONS: A greater percentage of central tumors show microscopic
      proximal bronchial extension, whereas the length of microscopic proximal
      bronchial extension is significantly greater in peripheral tumors. Peripheral
      tumors preferentially have a peribronchial extension pattern.

PMID- 11463557
TI  - Surgical treatment of lung cancer invading chest wall: a retrospective analysis
      of 110 patients.
AB  - OBJECTIVE: To retrospectively assess the results of surgical treatment in a
      consecutive series of 110 patients with Stage IIb and IIIa non small cell lung
      cancer (NSCLC) invading chest wall. METHODS: A series of 110 patients underwent
      surgery for Stage IIb and IIIa NSCLC with involvement of chest wall. There were
      101 male and 9 female patients, mean age was 61.4 (range 32--74), 52 (47.3%) of
      them complaining for chest pain. Surgical procedures were pneumonectomy in seven
      patients (6.4%), lobectomy in 73 (66.4%), bi-lobectomy in six (5.4%) and wedge
      resection in 24 (21.8%). In 63 patients (57.3%) an extrapleural resection was
      performed while in the other 47 (42.7%) an 'en bloc' resection of tumor with
      chest wall was required. In 22 patients (76.3%) repair was achieved by muscle
      flap while in 8 (26.7%) a prosthesis was required. Five-year survival was
      computed using the Kaplan--Meier method; P values correspond to the log-rank
      test. RESULTS: There were neither intraoperative nor postoperative deaths.
      Postoperative staging revealed 83 T3N0M0, 17 T3N1M0 and 10 T3N2M0. Mean
      postoperative hospital stay was 17.7 days (range 5--40). For N0 patients 5 year
      survival was 47% (39/83) and no significant difference was noted when
      extrapleural and 'en bloc' resection groups were compared (P = 0.08). In N1/N2
      patients no survival was observed (0/27) and comparison between surgical
      procedures was not statistically significant (P = 0.41). Moreover when N0
      patients were compared with N1 patients the difference in survival was
      significant for both extrapleural (P = 0.02) and 'en bloc' (P = 0.04) groups. No
      difference was noted when the two surgical procedures were compared independently
      form N status (P = 0.94). Within the group of patients undergone 'en bloc'
      resection survival was significantly better for N0 patients as in the group of
      extrapleural resection. CONCLUSION: Surgical treatment of Stage IIb and IIIa
      NSCLC invading chest wall by extrapleural or 'en bloc' resection is widely
      adopted and justified by the good results in terms of morbidity and relief of
      pain. Survival is always depending on the N status.

PMID- 11463558
TI  - Non-small cell lung cancer with single brain metastasis: the role of surgical
      treatment.
AB  - OBJECTIVE: The prognosis of non-small cell lung cancer (NSCLC) with brain
      metastasis is very poor, with median survival rate below 6 months, even if
      treated with palliative radio and/or chemotherapy. To assess the effectiveness of
      surgical treatment for this kind of patients we reviewed our experience. METHODS:
      From January 1989 to October 1999, 30 patients (26 males and four females; mean
      age: 58.7 years) with NSCLC and single brain metastasis underwent surgical
      treatment of both primary lung cancer and secondary cerebral lesion. Patients
      (pts) were divided into two major groups. In group 1 (G1) 20 pts (18 males and
      two females) presented a synchronous brain metastasis. In group 2 (G2) 10 pts
      (eight males and two females) presented a metachronous brain metastasis during
      the follow-up period (range 3-24 months since the primary tumor). Patients
      selected in G1 had T1-2, N0-1 clinical staging, good 'performance status' (ECOG:0
      -1; Karnofsky index > 70%), age < 75 years. Craniotomy has always been the first
      approach. In G2 also patients with locally advanced tumors (T3 and/or N2) were
      included. Whole brain radiotherapy and/or chemotherapy was the post-operative
      choice treatment. RESULTS: Histologic findings have shown: adenocarcinoma in 17
      cases (12 in G1; five in G2), squamous cell carcinoma in 10 cases (six in G1;
      four in G2), large cell carcinoma in 2 (one in G1; one in G2) and large cell
      neuroendocrine carcinoma in one (G1). Survival analysis (Kaplan--Meier method)
      has shown an overall value of 80% at 1 year (95% in G1; 50% in G2), 41% at 2
      years (47% in G1; 30% in G2) and 17% at 3 years (14% in G1; 20% in G2). Overall
      median survival is 23 months (23 in G1; 11 in G2); mean survival 27.8 months
      (30.3 months in G1; 22.8 months in G2). According to univariate analysis
      prognosis is definitively better in N0 tumors compared to N1-2 tumors and in
      adenocarcinoma cases compared to other histotypes (P < 0.05). CONCLUSIONS: We can
      conclude that combined surgical therapy is, nowadays, the choice treatment for
      this kind of patients, even though restricted to selected cases. The knowledge of
      prognostic factors may optimize indications for surgery.

PMID- 11463559
TI  - Evaluation of radiological and pathological prognostic factors in surgically
      treated patients with bronchoalveolar carcinoma.
AB  - OBJECTIVE: The incidence of adenocarcinoma and bronchoalveolar carcinoma has
      increased in recent years. The aim of this study was to retrospectively evaluate
      radiological and pathological factors affecting survival in patients with
      bronchoalveolar carcinoma (BAC) or BAC associated with adenocarcinoma who
      underwent surgical treatment. METHODS: From May 1988 to September 1999, 49
      patients with BAC or BAC and adenocarcinoma underwent surgical treatment.
      Complete resection was performed in 42 patients. In these patients the impact of
      the following factors on survival was evaluated: stage, TNM status, radiological
      and pathological findings (percentage of bronchoalveolar carcinoma in the tumour,
      presence or absence of sclerosing and mucinous patterns, vascular invasion and
      lymphocytic infiltration). RESULTS: Twenty-nine patients were male and 20 female.
      Mean age was 63 years. Five-year survival was 54%. Univariate analysis of the
      patients who underwent complete resection demonstrated a favourable impact on
      survival in stages Ia and Ib (P = 0.01) and in the absence of nodal involvement
      (P = 0.02) and mucinous patterns (P = 0.02). Mucinous pattern was also
      prognostically relevant at multivariate analysis (P = 0.02). In the 27 patients
      with stage Ia and Ib disease, univariate analysis demonstrated that the absence
      of mucinous pattern (P = 0.006) and a higher percentage of BAC (P = 0.01)
      favourably influenced survival. The latter data were also confirmed by
      multivariate analysis (P = 0.01). CONCLUSION: Surgical treatment of early-stage
      BAC and combined BAC and adenocarcinoma is associated with favourable results.
      However, the definition of prognostic factors is of utmost importance to improve
      the results of the treatment. In our series tumours of the mucinous subtype and
      with a lower percentage of BAC had a worse prognosis.

PMID- 11463560
TI  - Blood use in lung resection for carcinoma: perioperative elective anaemia does
      not compromise the early outcome.
AB  - OBJECTIVE: Blood transfusion may adversely affect the prognosis following surgery
      for non-small cell lung carcinoma (NSCLC). Conventionally by most thoracic
      surgeons, a perioperative haemoglobin (Hb) less than 10 g/dl has been considered
      a transfusion trigger. In this prospective trial we have (a) evaluated the
      overall blood transfusion requirements and factors associated with an increased
      need for transfusion and (b) in a subsequent subset of patients, tested the
      hypothesis that elective anaemia after major lung resection may be safely
      tolerated in the early postoperative period. METHODS: A total of 198 (M/F 179/10,
      mean age 61.2, range 32--85 years) patients suffering from NSCLC were submitted
      to pneumonectomy (n = 89), bilobectomy (n = 19) and lobectomy (n = 90). A rather
      strict protocol was used as a transfusion strategy. The transfusion requirements
      were analyzed and seven parameters (gender, age > 65, preoperative Hb < 11.5
      g/dl, chest wall resection, history of previous thoracotomy, pneumonectomy and
      total blood loss) were statistically evaluated by univariate and logistic
      regression analysis. Subsequently, according to the perioperative Hb level during
      the first 48 h, patients were divided into group A (n = 49, Hb = 8.5--10) and
      group B (n = 149, Hb > 10) with a view to estimate the risks of elective
      perioperative anaemia. Groups were comparable in terms of age, sex, type of
      operation performed, preoperative Hb, creatinine level, FEV1, arterial blood
      gases and history of heart disease. RESULTS: The overall transfusion rate was
      16%. Univariate analysis revealed that preoperative Hb < 11.5 g/dl (P < 0.01) and
      total blood loss (P < 0.0001) were associated with increased need for
      transfusion, but only the total blood loss was identified as an independent
      variable in multivariate analysis. Statistical analysis between groups A and B
      showed no significant difference regarding postoperative morbidity and mortality:
      atelectasis (3 vs. 6), chest infection (2 vs. 9), sputum retention requiring
      bronchoscopy (5 vs. 12), admission to intensive care unit (5 vs. 7), ARDS (0 vs.
      3), postoperative hospital stay (7.7 +/- 2.6 vs. 9.1 +/- 3.8 days) and deaths (1
      vs. 3). CONCLUSIONS: The use of a strict transfusion strategy could help in
      reducing overall blood transfusion. Furthermore, a perioperative Hb of 8.5--10
      g/dl could be considered safe in elective lung resections for carcinoma.

PMID- 11463561
TI  - Postoperative adjuvant therapy for stage IB non-small-cell lung cancer.
AB  - OBJECTIVE: Although surgical resection alone is considered adequate treatment in
      stage IB non-small-cell lung cancer (NSCLC), long-term survival is not
      satisfactory and the recurrence rate is quite high. The validity of postoperative
      chemotherapy at stage IB in terms of disease-free and overall survival was
      assessed in a randomised trial. METHODS: The trial was designed as a randomised,
      two-group study with postoperative adjuvant chemotherapy versus surgery alone as
      control group. All patients had stage IB disease (pT2N0) assessed after a radical
      surgical procedure. Chemotherapy consisted of treatment with cisplatin (100
      mg/m(2) on day 1) and etoposide (120 mg/m(2) on days 1--3) for a total of six
      cycles. RESULTS: Between January 1988 and December 1994, 66 patients were
      included in the study. Thirty-three belonged to the adjuvant chemotherapy group
      and 33 to the control group. Groups were homogeneous for conventional risk
      factors. There was no clinical significant morbidity associated to chemotherapy.
      Patients were followed for a minimum period of 5 years. The rates of locoregional
      recurrence and distant metastases were 18 and 30%, respectively, in the adjuvant
      chemotherapy group and 24 and 43%, respectively, in the control group. The 5-year
      disease-free survival rates were 59% in the adjuvant group and 30% in the control
      group (P = 0.02). The difference in the Kaplan--Meier survival between the groups
      was significant as assessed using the log-rank test (P = 0.04). CONCLUSIONS: Our
      results suggest that adjuvant chemotherapy may reduce recurrences and prolong
      overall survival in patients at stage IB NSCLC deemed radically operated. Despite
      being difficult to accept, the use of adjuvant chemotherapy might have better
      long-term results.

PMID- 11463562
TI  - Postoperative complications in relation with induction therapy for lung cancer.
AB  - OBJECTIVES: The purpose of this study was to evaluate the risk of lung cancer
      surgery following induction chemotherapy and/or radiotherapy. METHODS: This
      retrospective study included 69 patients treated from January 1990 to January
      1998 for a primary lung cancer in whom surgery had been performed after induction
      treatment. Surgery had not been considered initially for the following reasons:
      N2 disease (IIIA, n = 25); temporary functional impairment (two stages IB and two
      stages IIIA (N2), n = 4); and doubtful resectability (stage IIIB (T4), n = 40).
      The medical regimen resulted in combined radio-chemotherapy in 43 patients who
      received two to four cycles of chemotherapy (average 2.9 +/- 0.8 cycles) and 43
      +/- 8 Gy (range 20--60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7
      cycles). RESULTS: Exploratory thoracotomy was performed in four patients (6%).
      The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases.
      There were four re-operations (6%): three for bronchial fistula and one for
      bleeding. Thirty-five patients (51%) required blood transfusion (4.5 +/- 3.8 cell
      packs). The incidence of early and delayed bronchial fistula after pneumonectomy
      was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSIONS:
      Surgery for lung cancer after induction chemotherapy and/or radiotherapy is
      associated with an increased risk. If the mortality seems 'acceptable', the
      morbidity rate, however, is high.

PMID- 11463563
TI  - Small cell lung cancer I--III A: cytoreductive chemotherapy followed by resection
      with continuation of chemotherapy.
AB  - OBJECTIVES: To define the place for surgery in combined modality treatment of
      small cell lung cancer patients. The endpoint was: does complete resection reduce
      the risk of local failure? METHODS: Between November 1981 and June 1996, 75
      patients in stage I--III A, many of them with a bulky cN2 tumor at presentation,
      were exposed to VP-16 based cytoreductive chemotherapy. After three courses of
      induction treatment, 46 patients underwent thoracotomy and 35 of them had
      resection. RESULTS: There were two sudden deaths (pulmonary embolism). No other
      complications were observed. In six cases (6/35 = 16%), no residual tumor was
      found in the resected specimen. Four weeks after surgery, chemotherapy was
      resumed. Three patients experienced local relapse (3/33), among them, the single
      patient with incomplete resection, and two other patients developed local and
      distant failure (2/33). Thus, the local relapse rate was 15% (5/33). Eight
      patients, mainly with chemotherapy induced surgicopathological complete remission
      (pCR) and with lymph nodes free of tumor in surgical specimens (pN0), are alive,
      tumor-free, at a median of 136 + months. Two patients died tumor-free at 65 and
      147 months. One patient died of unrelated causes at 21 months with no evidence of
      disease at autopsy. The median survival in the cN0 + N1 subsets was 25.09 months,
      whereas in cN2 disease, this was 13.75 months. There were no long-term survivors
      among the patients with persistent N2 disease. The median survival in all 35
      patients using the Kaplan--Meier method was 18 months; the 5-year tumor-free
      survival rate was 29% and the 10-year tumor-free survival rate was 23%.
      CONCLUSIONS: Satisfactory local tumor control confirmed the assumption of the
      study. No residual tumor in the resected specimen (pCR) is the most favorable
      prognostic factor and determinant of long-term survival. Surgery should not be
      performed in the patients with persistent N2 disease.

PMID- 11463564
TI  - Indications for surgery in tracheobronchial ruptures.
AB  - OBJECTIVE: Ruptures of the tracheobronchial tree present a life-threatening
      situation. Nevertheless, therapy is still controversial. Though conservative
      treatment by antibiotics and intubation with the cuff inflated distal to the tear
      is favored by some authors, surgical repair is unavoidable in many cases.
      METHODS: We present a series of 31 patients (mean age 43.6 years, range 8--72
      years) with iatrogenous or post-traumatic tracheobronchial ruptures treated since
      1975. Fifteen ruptures were longitudinal tears of the trachea, not extending
      lower than a distance of 3 cm from the bifurcation, 11 involved the bifurcation
      and/or the main bronchi. The total length of the longitudinal tears ranged from 2
      to 12 cm, five were transverse near complete abruptions of the trachea or main
      bronchi. Involvement of the full thickness of the wall with free view into the
      pleural space or to the esophageal wall was present in 29 cases. Twenty-nine out
      of the 31 patients underwent surgical repair and two were treated conservatively.
      The length and depth of the lesion, the degree of subcutaneous emphysema,
      pneumothorax and/or pneumomediastinum as well as clinical signs suggesting
      incipient mediastinitis were considered when making the decision for surgery.
      RESULTS: Twenty-five out of the 29 patients experienced an uneventful recovery.
      Four patients died of sepsis unrelated to the tracheobronchial trauma. One of the
      two patients who underwent conservative therapy also recovered uneventfully. The
      other one died because of multi-organ failure due to underlying myocardial
      infarction. CONCLUSIONS: Conveniently localized short lacerations, especially if
      they do not involve the whole thickness of the tracheal wall, can be treated with
      antibiotics and intubation with the cuff inflated distal to the tear, avoiding
      high intra-bronchial pressures also after eventual extubation. In all other cases
      surgical repair is to be preferred.

PMID- 11463565
TI  - Surgical treatment of esophageal carcinoma complicated by fistulas.
AB  - OBJECTIVES: The locally advanced esophageal carcinoma can be complicated by
      fistulas. According to published data, the incidence rate of malignant esophageal
      fistulas is about 13%. The range of treatment modalities proposed by different
      authors varies from palliation to active and, if possible, radical surgical
      interventions. In the present study, we investigated combined esophagectomies as
      a radical treatment of the malignant esophageal fistulas. METHODS: Thirty-five
      patients (aged 28--67) with malignant esophageal fistulas of different
      localizations were operated over a period from 1990 to 2000. The tumor was
      located in the upper, middle and lower thoracic esophagus in four, 20 and 11
      cases, respectively. The malignant fistula with the mediastinum, pleural cavity,
      lungs, bronchi and trachea was observed in 21, two, five, four and three cases,
      respectively. Subtotal esophagectomy and esophagogastroplasty were performed in
      18 patients; subtotal esophagectomy with intrapleural coloesophagoplasty was
      performed in one case; proximal gastric and lower thoracic esophageal resection
      from the left-side abdominothoracic approach was performed in three cases.
      Esophagogastric bypass anastomoses were formed in ten patients. Gastrostomy was
      performed in three patients. RESULTS: The complication rate was 40% (14 out of
      35); the postoperative mortality was 14.3% (five out of 35). In patients after
      esophageal resection, the mortality rate was 13.6% (three out of 22). With a
      median survival of 13 months (range, 3--31), the 2-year survival rate was 21%
      after combined esophagectomies. CONCLUSIONS: The goal of surgery for esophageal
      cancer with various fistulas is to completely resect the primary tumor and
      involved adjacent structures with clear surgical margins and extended two-field
      lymphadenectomy. The importance of performing a complete resection is stressed by
      the absence of 1-year survivors among patients who underwent bypass surgery or
      gastrostomy. We consider that en-bloc combined resection of esophageal cancer
      complicated by fistula can be done with a low mortality.

PMID- 11463566
TI  - Post-traumatic pericardial rupture.

PMID- 11463567
TI  - Mediastinoscopy and permanent venous access device positioning through the same
      incision.
AB  - We report herein our technique for positioning of permanent venous access device
      in patients undergoing mediastinoscopy for diagnosis and/or staging of thoracic
      malignancies. Through the same 3-cm skin incision employed for mediastinoscopy,
      access to right internal jugular vein is obtained and the prepectoral pocket for
      chamber positioning is prepared. The technique is simple, safe and provides
      increased patient acceptability.

PMID- 11463568
TI  - A novel technique for giant left atrium reduction.
AB  - We herein describe a safe and reproducible technique for left atrial volume
      reduction in patients with a giant left atrium. In a 56-year-old patient
      undergoing redo mitral valve replacement, the left atrium measured 18 x 20 x 17
      cm occupying the middle-lower segment of the right hemithorax with compression of
      the adjacent organs. The left atrial volume was reduced by triangular resections
      of the atrial wall and the mitral valve was replaced using a mechanical
      prosthesis. The postoperative course was uneventful and the left atrial diameter
      was 11.2 cm at the latest control.

PMID- 11463569
TI  - Thoracic epidural anesthesia for coronary bypass via left anterior thoracotomy in
      the conscious patient.
AB  - Cardiac surgery is perceived to be maximally invasive and fraught with
      complications. Secondary to this, cardiothoracic surgeons have been refining
      traditional techniques to minimize their invasive nature. Epidural anesthesia has
      been utilized safely and effectively for numerous surgical procedures to reduce
      the associated morbidity. In hopes of achieving a similar result, we utilized
      thoracic epidural anesthesia for a coronary artery bypass via a left anterior
      thoracotomy, in an awake, spontaneously breathing patient. To the best of our
      knowledge, this is the first reported case utilizing this approach. Herein we
      report the results and technique utilized.

PMID- 11463570
TI  - Mediastinitis following graft replacement of the ascending aorta: conservative
      approach by omental transposition.
AB  - A 57-year-old patient underwent prosthetic replacement of a previously implanted
      ascending aorta graft and developed a periprosthetic purulent collection 1 month
      later. He was successfully treated by debridement of infected tissues, antiseptic
      irrigation and transposition of an omental flap. The postoperative course was
      uneventful. A chest computed tomography scan performed 15 months later showed no
      signs of perigraft infection. Prompt conservative surgical treatment including
      omental transposition can be effective in the treatment of mediastinitis
      following graft replacement of the ascending aorta.

PMID- 11463571
TI  - Long-term survival after multiple resections of a fibrosarcoma involving the lung
      and chest wall.
AB  - We report on the case of a 61-year-old male patient who developed a giant
      fibrosarcoma involving both the lung and chest wall. This patient underwent three
      extended resections including the chest wall in each case. Radiotherapy was
      administered after the last resection, when the tumor was obviously not
      completely removed. The patient lives a normal life with no signs of recurrence 5
      years after his last resection. Multiple extended resections of large and
      aggressive sarcomas can result in long-term survival, with good quality of life,
      in adequately selected patients.

PMID- 11463572
TI  - Peroxisome proliferator-activated receptor-gamma: from adipogenesis to
      carcinogenesis.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone
      receptors, initially described as molecular targets for synthetic compounds
      inducing peroxisome proliferation. PPAR-gamma, the best characterized of the
      PPARs, plays a crucial role in adipogenesis and insulin sensitization.
      Furthermore, PPAR-gamma has been reported to affect cell
      proliferation/differentiation pathways in various malignancies. We discuss in the
      present review recent advances in the understanding of the function of PPAR-gamma
      in both cell proliferation and adipocyte differentiation.

PMID- 11463573
TI  - Mutations in the human genes encoding the transcription factors of the hepatocyte
      nuclear factor (HNF)1 and HNF4 families: functional and pathological
      consequences.
AB  - Mutations in the human genes encoding the tissue-specific transcription factors
      hepatocyte nuclear factor (HNF)1alpha, HNF1beta and HNF4alpha are responsible for
      maturity onset diabetes of the young (MODY), a monogenic dominant inherited form
      of diabetes mellitus characterized by defective insulin secretion of the
      pancreatic beta-cells. In addition, the mutated HNF1beta gene causes defective
      development of the kidney and genital malformation. This review summarizes the
      main features of these transcription factors and discusses potential events
      leading to the specific disease phenotypes.

PMID- 11463574
TI  - Alternative splicing of the proadrenomedullin gene results in differential
      expression of gene products.
AB  - The adrenomedullin (AM) gene codifies for two bioactive peptides, AM and proAM N
      terminal 20 peptide (PAMP). We have found two forms of the AM mRNA. Form A is
      devoid of introns and results in a prohormone containing both peptides. Form B
      retains the third intron, which introduces a premature stop codon, producing a
      shorter prohormone with only PAMP. Tissues with a higher B/A ratio were more
      immunoreactive for PAMP than for AM. The form B message was found in the
      cytoplasmic compartment, thus excluding that the longer message was a result of
      contaminating nuclear mRNA. Form B was found in cells that express PAMP but not
      AM. mRNA expression in a variety of cell lines was investigated by ribonuclease
      protection assay and form B was found in significant amounts in two of them.
      Treatments that modify AM expression, such as exposure to hypoxia, were shown to
      change the B/A ratio and the relative secretion of AM and PAMP, indicating that
      the splicing mechanism for AM can be modulated and is physiologically relevant.
      Analysis of the sequence of the third intron and the fourth exon of the AM gene
      found motifs compatible with a highly regulated alternative splicing mechanism.

PMID- 11463575
TI  - Regulation of apoA1 gene expression with acidosis: requirement for a
      transcriptional repressor.
AB  - Serum apolipoprotein A(1) (apoA(1)) concentration is inversely correlated with
      the risk of premature atherosclerosis. Serum apoA(1) concentrations are
      regulated, in part, at the transcriptional level. ApoA(1) mRNA is synthesized
      primarily in the liver and small intestine, under the direction of a number of
      signaling molecules and tissue-specific regulatory elements. Previously, we
      demonstrated that extracellular acidosis suppresses apoA(1) mRNA levels at the
      level of transcription. Here we demonstrate that intracellular acidosis, in the
      absence of extracellular pH changes, represses apoA(1) promoter activity.
      Repression occurs through a pH responsive element (pH-RE) located within the
      apoA(1) gene promoter. Acidosis increases the specific DNA binding activity of a
      putative repressor protein within the immediate 5'-flanking region of the apoA(1)
      gene. The cis-element that binds the putative repressor protein contains a
      negative thyroid hormone response element (nTRE) located 3' and adjacent to the
      apoA(1) TATA box. Mutation of the nTRE/pH-RE abrogates protein binding and alters
      the activity of reporter genes controlled by this element. Repression by acidosis
      did not require de novo mRNA and protein synthesis. Inhibition of tyrosine kinase
      activity and diacylglycerol-stimulated protein kinase C (PKC) signaling pathways
      with tyrophostin A47 and phorbol myristate acetate, respectively, did not affect
      the repression of apoA(1) promoter activity with acidosis. These results suggest
      that transcriptional repression of the apoA(1) gene by alterations in ambient pH
      is associated with enhanced DNA binding activity of a repressor protein, through
      a mechanism which appears to be independent of de novo mRNA and protein
      synthesis, tyrosine kinase activity, or PKC activation.

PMID- 11463576
TI  - Thyroid transcription factor 1 and Pax8 synergistically activate the promoter of
      the human thyroglobulin gene.
AB  - Thyroglobulin (Tg) is an essential thyroid-specific protein, which serves as the
      matrix for thyroid hormone biosynthesis. To obtain new insights in the regulation
      of Tg gene expression, we investigated the interaction of the human Tg promoter
      with the thyroid-specific transcription factors TTF-1 and Pax8. A reporter gene,
      containing a 202 bp fragment from the human Tg 5'-flanking region including the
      promoter sequence and the transcriptional start site, and expression vectors
      containing the cDNAs for human TTF-1 and Pax8 were used in cotransfection
      experiments, in the non-thyroidal cell lines COS-7 and HeLa. Pax8 increased the
      specific transcriptional activity of the Tg promoter about threefold, whereas
      cotransfection with the homeodomain-containing protein TTF-1 stimulated promoter
      activity from six- to tenfold. The simultaneous expression of both factors
      stimulated the Tg promoter activity in a multiplicative manner up to 25-fold. TTF
      1 binding sites could be localized precisely by lectron mobility shift assay. The
      two binding elements corresponded to sites A and C in the rat Tg promoter. Site
      directed mutagenesis of three nucleotides in each binding element inhibited
      binding of TTF-1 to the two oligonucleotides. In cotransfection experiments, the
      mutant site C decreased TTF-1 transactivation to 26% of the wild-type, whereas an
      additional mutation in the site A reduced this value to almost zero, thus proving
      the physiological relevance of these sites. The present results demonstrate that
      the activity of the human Tg promoter is closely dependent on the function of TTF
      1 and Pax8, opening the field for further investigations of pathological
      alterations of Tg gene expression.

PMID- 11463577
TI  - The first international standard for human leptin and the first international
      standard for mouse leptin: comparison of candidate preparations by in vitro
      bioassays and immunoassays.
AB  - In an international collaborative study, two preparations of human sequence
      recombinant leptin and two preparations of mouse sequence recombinant leptin were
      evaluated, using in vitro bioassays and immunoassays, by eight laboratories, in
      three countries, for their suitability to serve as the international standard
      (IS) for human and mouse leptin respectively. The bioassays detected the human
      and mouse leptin with similar potency, while the immunoassays showed a greater
      response to the leptin of the species against which the antibody preparation had
      been raised. Comparison of the candidate standards with the various preparations
      of leptin of the same species currently assayed in the participating laboratories
      showed that immunoassay measurements cannot be used to predict the biological
      potency. On the basis of the results reported here, in October 1999 the Expert
      Committee on Biological Standardization of the World Health Organization
      established the preparation coded 97/594 as the first IS for human leptin, with
      an assigned unitage of 4000 IU/ampoule, and the preparation coded 97/626 as the
      first IS for mouse leptin, with an assigned unitage of 4000 IU/ampoule. The ISs
      for leptin are distributed by the National Institute for Biological Standards and
      Control, UK, http://www.nibsc.ac.uk.

PMID- 11463578
TI  - The engineered, cytosolic form of human type I 3beta-hydroxysteroid
      dehydrogenase/isomerase: purification, characterization and crystallization.
AB  - Human type I 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD/isomerase)
      is an integral membrane protein of human placental trophoblast and of insect Sf9
      cells transfected with recombinant baculovirus containing the cDNA encoding the
      enzyme. Purified native or wild-type enzyme remains in solution only in the
      presence of detergent that may prevent crystallization. The membrane-spanning
      domain (residues 283-310) of the enzyme protein was deleted in the cDNA using PCR
      based mutagenesis. The modified enzyme was expressed by baculovirus in the
      cytosol instead of in the microsomes and mitochondria of the Sf9 cells. The
      cytosolic form of 3beta-HSD/isomerase was purified using affinity chromatography
      with Cibacron Blue 1000. The NAD(+) and NaCl used to elute the enzyme were
      removed by size-exclusion centrifugation. Hydroxylapatite chromatography yielded
      a 26-fold purification of the enzyme. SDS-PAGE revealed a single protein band for
      the purified cytosolic enzyme (monomeric molecular mass 38.8 kDa) that migrated
      just below the wild-type enzyme (monomeric molecular mass 42.0 kDa). Michaelis
      Menten constants measured for 3beta-HSD substrate (dehydroepiandrosterone)
      utilization by the purified cytosolic enzyme (K(m)=4.5 microM, V(max)=53 nmol/min
      per mg) and the pure wild-type enzyme (K(m)=3.7 microM, V(max)=43 nmol/min per
      mg), for isomerase substrate (5-androstene-3,17-dione) conversion by the purified
      cytosolic (K(m)=25 microM, V(max)=576 nmol/min per mg) and wild-type (K(m)=28
      microM, V(max)=598 nmol/min per mg) enzymes, and for NAD(+) reduction by the
      3beta-HSD activities of the cytosolic (K(m)=35 microM, V(max)=51 nmol/min per mg)
      and wild-type (K(m)=34 microM, V(max)=46 nmol/min per mg) enzymes are nearly
      identical. The isomerase activity of the cytosolic enzyme requires allosteric
      activation by NADH (K(m)=4.6 microM, V(max)=538 nmol/min per mg) just like the
      wild-type enzyme (K(m)=4.6 microM, V(max)=536 nmol/min per mg). Crystals of the
      purified, cytosolic enzyme protein have been obtained. The inability to
      crystallize the detergent-solubilized, wild-type microsomal enzyme has been
      overcome by engineering a cytosolic form of this protein. Determining the
      tertiary structure of 3beta-HSD/isomerase will clarify the mechanistic roles of
      potentially critical amino acids (His(261), Tyr(253)) that have been identified
      in the primary structure.

PMID- 11463579
TI  - Homocysteine thiolactone inhibits insulin signaling, and glutathione has a
      protective effect.
AB  - Hyperhomocysteinemia and insulin resistance are independent factors for
      cardiovascular disease. Most of the angiotoxic effects of homocysteine are
      related to the formation of homocysteine thiolactone and the consequent increase
      in oxidative stress. The oxidative stress has also been shown to impair insulin
      action, therefore leading to insulin resistance. In order to study a putative
      direct effect of homocysteine on insulin signaling, we have characterized the
      molecular counter-regulation of the early events in the signal transduction of
      the insulin receptor, and the metabolic end-point of glycogen synthesis. We
      employed HTC rat hepatoma cells transfected with the human insulin receptor. A 10
      min exposure to homocysteine thiolactone (50 microM) resulted in a significant
      inhibition of insulin-stimulated tyrosine phosphorylation of the insulin receptor
      beta-subunit and its substrates IRS-1 and p60-70, as well as their association
      with the p85 regulatory subunit of phosphatidylinositol 3-kinase. These effects
      led to impairment of the insulin-stimulated phosphatidylinositol 3-kinase
      activity, which plays a central role in regulating insulin action. Thus, insulin
      stimulated glycogen synthesis was also inhibited by homocysteine thiolactone. To
      investigate whether oxidative stress was mediating the counter-regulatory effect
      of homocysteine thiolactone on insulin signaling, we preincubated the cells (5
      min) with 250 microM glutathione prior to the incubation with homocysteine (10
      min) and subsequent insulin challenge. Glutathione completely abolished the
      effects of homocysteine thiolactone on insulin-receptor signaling and restored
      the insulin-stimulated glycogen synthesis. In conclusion, these data suggest that
      homocysteine thiolactone impairs insulin signaling by a mechanism involving
      oxidative stress, leading to a defect in insulin action.

PMID- 11463580
TI  - Cross-talk between Stat5b and estrogen receptor-alpha and -beta in mammary
      epithelial cells.
AB  - Both 17beta-estradiol and prolactin play important roles in the mammary gland,
      raising the possibility of functional cross-talk between the two signaling
      pathways. Here, we demonstrate that estrogen receptor-alpha (ERalpha) and -beta
      (ERbeta) are both able to potentiate transcription from a Stat5-responsive
      promoter when activated by prolactin. Potentiation was observed not only in the
      presence of 17beta-estradiol, but also in the presence of anti-estrogens such as
      tamoxifen and ICI 182,780. The magnitude of the response was dependent on cell
      type: in the HC11 mouse mammary epithelial cell line ERbeta potentiates
      transcription efficiently whereas ERalpha showed low activity. Conversely, in COS
      7 cells, both estrogen receptors were active. We show that activation domains in
      the N-terminus (AF-1) and the C-terminus (AF-2) of the ERs are dispensable for
      potentiation. The effects are dependent on the presence of an intact DNA
      binding/hinge domain, which we show is capable of interacting with Stat5b in
      vitro and in HC11 cell extracts. We conclude that ERalpha and ERbeta act as
      coactivators for Stat5b through a mechanism which is independent of AF-1 and AF
      2.

PMID- 11463581
TI  - Association of prohormone convertase 3 with membrane lipid rafts.
AB  - Prohormone convertase 3 (PC3) is a neuroendocrine-specific member of the
      subtilisin-kexin family, involved in the intracellular processing and maturation
      of prohormones and proneuropeptides. PC3 is synthesised as a proprotein that
      undergoes two different cleavages resulting in the mature PC3 and the
      enzymatically active PC3DeltaC. In vitro translated proPC3 and proPC3DeltaC bind
      to trans-Golgi network (TGN)/granule-enriched membranes from the AtT20
      neuroendocrine cell line in a pH-dependent manner suggesting both a dominant role
      for the pro-region in membrane association and that the C-terminal region is not
      essential. However, while PC3 bound to membranes the majority of PC3DeltaC did
      not, suggesting that either the pro-region or the C-terminal region of PC3 is
      required for membrane association. Removal of peripheral membrane proteins did
      not affect the binding properties of any of the in vitro translated proteins.
      Chromaffin granule membranes (CGMs) were used to study the binding
      characteristics of endogenous PC3 and its active C-terminal truncated counterpart
      (PC3DeltaC). Incubation of CGMs with Triton X-100 did not completely solubilise
      either of these forms of PC3. Moreover, both PC3 and PC3DeltaC remained
      associated with detergent-resistant membrane microdomains, termed lipid rafts,
      purified from CGMs. The data raise the possibility that PC3 and PC3DeltaC are
      sorted to the regulated secretory pathway via their association with membrane
      lipid rafts.

PMID- 11463582
TI  - Idiopathic pulmonary fibrosis: to biopsy or not to biopsy.

PMID- 11463583
TI  - Following protocol: weaning difficult-to-wean patients with chronic obstructive
      pulmonary disease.

PMID- 11463584
TI  - Upper airway nerve lesions in obstructive sleep apnea.

PMID- 11463585
TI  - Safeguarding patients in clinical trials with high mortality rates.

PMID- 11463586
TI  - Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis.
AB  - It is not known if a surgical lung biopsy is necessary in all patients for the
      diagnosis of idiopathic pulmonary fibrosis (IPF). We conducted a blinded,
      prospective study at eight referring centers. Initially, cases were evaluated by
      clinical history and examination, transbronchial biopsy, and high-resolution lung
      computed tomography scans. Pulmonologists at the referring centers then assessed
      their certainty of the diagnosis of IPF and provided an overall diagnosis, before
      surgical lung biopsy. The lung biopsies were reviewed by a pathology core and 54
      of 91 patients received a pathologic diagnosis of IPF. The positive predictive
      value of a confident (certain) clinical diagnosis of IPF by the referring centers
      was 80%. The positive predictive value of a confident clinical diagnosis was
      higher, when the cases were reviewed by a core of pulmonologists (87%) or
      radiologists (96%). Lung biopsy was most important for diagnosis in those
      patients with an uncertain diagnosis and those thought unlikely to have IPF.
      These studies suggest that clinical and radiologic data that result in a
      confident diagnosis of IPF by an experienced pulmonologist or radiologist are
      sufficient to obviate the need for a lung biopsy. Lung biopsy is most helpful
      when clinical and radiologic data result in an uncertain diagnosis or when
      patients are thought not to have IPF.

PMID- 11463587
TI  - Ace gene I/D polymorphism and sarcoidosis pulmonary disease severity.
AB  - Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin
      converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic
      heterogeneity of I/D frequencies and controversy surrounding the association
      between the polymorphism and severity of disease. The objective of this study
      was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease
      susceptibility, (2) pulmonary disease severity (with particular reference to
      pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct
      European sarcoidosis populations. Standard chest radiographic staging was
      performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from
      presentation. Pulmonary function data were analyzed, and patients were then
      categorized according to disease severity. A PCR-SSP assay was used to determine
      the ACE I/D genotype of each patient studied. The I/D allele frequencies from
      these patients were compared with frequencies from ethnically matched UK (n =
      386) and Czech (n = 179) control subjects using a chi-square contingency table.
      No significant differences were seen in the distribution of the ACE I/D
      genotypes, allele frequencies or phenotype frequencies. Furthermore, no
      association was found between the ACE I/D polymorphism and pulmonary disease
      severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism
      has no role in sarcoidosis susceptibility in European whites and that it is not a
      regulatory variant in this disease.

PMID- 11463588
TI  - Pulmonary gas exchange and sputum cellular responses to inhaled leukotriene D(4)
      in asthma.
AB  - Inhalational challenges with inflammatory mediators may provoke lung function
      disturbances similar to those shown in spontaneous acute asthma. Cysteinyl
      leukotrienes (CysLTs) have recently been established as mediators of
      bronchoconstriction in asthma but their effects on pulmonary gas exchange in
      asthma have not been assessed. We therefore investigated the effects of
      leukotriene D(4) (LTD(4)) challenge resulting in a significant decrease in FEV(1)
      (mean +/- SE, by 32 +/- 3%) in 13 nonsmoking, mild asthmatics. Respiratory system
      resistance (Rrs), and respiratory and inert gases were measured before and
      immediately after, and at 15 and 45 min after challenge. After
      bronchoprovocation, Rrs increased (by 106 +/- 12%), Pa(O(2)) decreased (by 25 +/-
      4 mm Hg), and ventilation-perfusion distributions moderately to severely
      deteriorated, as shown by increases in the dispersions of pulmonary blood flow
      (Log SDQ, by 59 +/- 12%) and alveolar ventilation (Log SDV, by 65 +/- 20%) (p <
      0.05 each). Sputum eosinophils (p < 0.05) and urinary LTE(4) (p < 0.005)
      increased after challenge. Despite the lack of mathematical correlations between
      spirometric and Rrs changes and gas exchange indices, the pattern of improvement
      of the functional variables after challenge ran in parallel. These findings
      support the evidence that CysLTs, in addition to being potent
      bronchoconstrictors, also provoke profound disturbances of pulmonary gas exchange
      in asthma.

PMID- 11463589
TI  - Airway constriction pattern is a central component of asthma severity: the role
      of deep inspirations.
AB  - Measurements of lung resistance and elastance (RL and EL) from 0.1 to 8 Hz
      reflect both the mean level and pattern of lung constriction. The goal of this
      study was to establish a relation between a deep inspiration (DI) and the
      heterogeneity of constriction in healthy versus asthmatic subjects. Constriction
      pattern was assessed from measurements of the RL and EL from 0.1 to 8 Hz in seven
      healthy subjects and in 12 asthmatics. These data were acquired before and after
      a DI and before and after a standard methacholine challenge versus a modified
      challenge in which a DI is prohibited. Generally, avoidance of a DI increased
      responsiveness. In healthy subjects and in those with mild-to-moderate baseline
      asthma a bronchial challenge, especially during self-inhibited DI, produced a
      heterogenous pattern of constriction inclusive of randomly distributed airway
      closures or near closures. Nevertheless, such subjects were able to reopen their
      airways via a DI. In contrast, in subjects with severe baseline asthma, there is
      a more extreme heterogeneous constriction pattern with random airway closures
      even at baseline. Further, there is no residual bronchodilatory effect of a DI
      either before or after bronchial challenge. We conjecture that inflammation and
      wall-remodeling facilitate a dangerous degree of heterogeneous constriction
      inclusive of airway closures or near closures, and contribute to the prevention
      of a DI from having a residual bronchodilatory effect.

PMID- 11463590
TI  - Airway narrowing associated with inhibition of deep inspiration during
      methacholine inhalation in asthmatics.
AB  - Reduced bronchodilatation in response to deep inspiration (DI) has been
      demonstrated in asthmatics. We have previously shown that inhibition of DI for 10
      min or more during methacholine inhalation increases airway narrowing in normals.
      We tested the hypothesis that inhibition of DIs during methacholine inhalation in
      asthmatics would not affect the magnitude of airway narrowing. We administered
      the PC(15) dose of methacholine to eight asthmatics every 5 min for 5 doses and
      measured spirometry after each dose. On four separate days, subjects received
      either 2, 3, 4, or 5 doses selected randomly, but DIs were inhibited during the
      challenge and spirometry was measured only at the start and after the final dose.
      Geometric mean PC(15) was 1.6 mg/ml. Mean values for FEV(1) (+/- SEM) after Doses
      2 through 5 were 84 +/- 4, 78 +/- 6, 79 +/- 5, and 81 +/- 3% of baseline,
      respectively, when DIs were allowed. During inhibition of DIs, they were 73 +/-
      6, 67 +/- 5, 64 +/- 6, and 61 +/- 7% of baseline values. Decreases in FEV(1)
      after Doses 4 and 5 were significantly greater when DIs were inhibited (p <
      0.05). We conclude that in this group of asthmatics, inhibition of DI for 15 min
      is associated with increased airway narrowing in response to methacholine
      inhalation, and therefore, DI may be an important factor limiting induced airway
      narrowing in asthmatics as well as in normal subjects.

PMID- 11463591
TI  - "Natural history" of pulmonary hypertension in a series of 131 patients with
      chronic obstructive lung disease.
AB  - The prognostic value and the evolution of pulmonary hypertension (PH) in patients
      with markedly hypoxemic chronic obstructive pulmonary disease (COPD), treated or
      not with long-term oxygen therapy (LTOT), has been extensively investigated.
      However, little is known in patients with mildly or moderately hypoxemic COPD not
      requiring LTOT. Therefore, we assessed the evolution of pulmonary hemodynamics in
      131 patients with stable COPD by performing two right heart catheterizations at a
      mean (+/- SD) time interval of 6.8 +/- 2.9 yr. At inclusion (T0), no patient had
      PH (i.e., the mean pulmonary artery pressure [Ppa] at rest was < 20 mm Hg). Group
      1 included 55 patients without exercising PH and group 2 included 76 patients
      with exercising PH, defined by a pulmonary arterial pressure (Ppa) > 30 mm Hg
      during a steady-state 40-W exercise. Group 2 patients compared with group 1
      patients had a significantly higher resting Ppa (16 +/- 3 mm Hg versus 14 +/- 2
      mm Hg, p = 0.001). At the second catheterization, 33 (25%) patients (9 of 55 in
      group 1, 24 of 76 in group 2, p = 0.048) showed a resting Ppa > 20 mm Hg, but PH
      was generally mild, ranging from 20 to 42.5 mm Hg. The mean Ppa at second
      evaluation was 16 +/- 5 mm Hg in group 1 and 19 +/- 7 mm Hg in group 2 (p =
      0.01). The patients who developed resting PH at the second catheterization (T1)
      had higher resting and exercising Ppa (p = 0.001 and p = 0.002, respectively),
      and significantly lower resting and exercising Pa(O(2)) (p = 0.005 and p = 0.012,
      respectively) at T0. Logistic regression analysis showed that resting and
      exercising Ppa were independent predictors (at T0) for the subsequent development
      of PH (p = 0.029 and p = 0.027, respectively). The patients who developed resting
      PH (T1) had a significantly worsening of Pa(O(2)) (from 63.5 mm Hg at T0 to 60 mm
      Hg at T1, p = 0.047), whereas the Pa(O(2)) as a mean was stable in the remainder
      (69.5 mm Hg at T0 and T1). These results show the following. The progression of
      Ppa over time in patients with COPD with mild to moderate hypoxemia is rather
      slow, the average change for the group as a whole being of + 0.4 mm Hg/yr. Only
      about 25% of patients with COPD with mild to moderate hypoxemia and without
      resting PH at the onset will develop PH during a 6-yr follow-up. The patients
      with exercising PH at the onset have a significantly increased risk of developing
      PH over time. Only resting and exercising Ppa at the onset are independently
      related to the subsequent development of PH. However, in individual cases, the
      models of linear or logistic regression do not allow a pertinent prediction of
      the level of Ppa or the presence of PH at the second right heart catheterization.

PMID- 11463592
TI  - Comparison of two methods for weaning patients with chronic obstructive pulmonary
      disease requiring mechanical ventilation for more than 15 days.
AB  - We designed a prospective multicenter randomized controlled study in three long
      term weaning units (LWU) to evaluate which protocol, inspiratory pressure support
      ventilation (PSV) or spontaneous breathing trials (SB), is more effective in
      weaning patients with chronic obstructive pulmonary disease (COPD) requiring
      mechanical ventilation for more than 15 d. Fifty-two of 75 patients, failing an
      initial T-piece trial at admission, were randomly assigned to PSV or SB (26 in
      both groups). No significant difference was found in weaning success rate (73%
      versus 77% in the PSV and SB group, respectively), mortality rate (11.5% versus
      7.6%), duration of ventilatory assistance (181 +/- 161 versus 130 +/- 106 h), LWU
      (33 +/- 12 versus 35 +/- 19 d), or total hospital stay. The results of these
      defined protocols were retrospectively compared with an "uncontrolled clinical
      practice" in weaning historical control patients. The overall 30-d weaning
      success rate was significantly greater (87% versus 70%) and the time spent under
      mechanical ventilation by survived and weaned patients was shorter in the
      patients in the study than in historical control patients (103 +/- 144 versus 170
      +/- 127 h). The LWU and hospital stays were also significantly shorter (27 +/- 12
      versus 38 +/- 18 and 38 +/- 17 versus 47 +/- 18 d). Spontaneous breathing trials
      and decreasing levels of PSV are equally effective in difficult-to-wean patients
      with COPD. The application of a well-defined protocol, independent of the mode
      used, may result in better outcomes than uncontrolled clinical practice.

PMID- 11463593
TI  - Efficacy of low tidal volume ventilation in patients with different clinical risk
      factors for acute lung injury and the acute respiratory distress syndrome.
AB  - In patients with acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low
      tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by
      22% compared with traditional mechanical ventilation (12 ml/kg). In this study,
      we examined the relative efficacy of low VT mechanical ventilation among 902
      patients with different clinical risk factors for ALI/ARDS who participated in
      ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS
      was associated with substantial variation in mortality. The risk of death (before
      discharge home with unassisted breathing) was highest in patients with sepsis
      (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other
      risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite
      these differences in mortality, there was no evidence that the efficacy of the
      low VT strategy varied by clinical risk factor (p = 0.76, for interaction between
      ventilator group and risk factor). There was also no evidence of differential
      efficacy of low VT ventilation in the other study outcomes: proportion of
      patients achieving unassisted breathing (p = 0.59), ventilator-free days (p =
      0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for
      demographic and clinical covariates did not appreciably affect these results.
      After reclassifying the clinical risk factors as pulmonary versus nonpulmonary
      predisposing conditions and infection-related versus non-infection-related
      conditions, there was still no evidence that the efficacy of low VT ventilation
      differed among clinical risk factor subgroups. In conclusion, we found no
      evidence that the efficacy of the low VT ventilation strategy differed among
      clinical risk factor subgroups for ALI/ARDS.

PMID- 11463594
TI  - Effects of high-frequency oscillation on endogenous surfactant in an acute lung
      injury model.
AB  - This study evaluated the effects of high-frequency oscillation (HFO) and
      conventional mechanical ventilation (CMV) on gas exchange and the pulmonary
      surfactant system in an acute lung injury model. Following induction of lung
      injury with N-nitroso-n-methylurethane, adult rabbits were anesthetized and
      randomized to one of the following ventilatory strategies: HFO for 120 min, CMV
      for 120 min, HFO for 60 min, followed by CMV for 60 min, CMV for 60 min followed
      by HFO for 60 min or CMV for 60 min. Separate animals were ventilated using CMV
      with a lower tidal volume and a positive end-expiratory pressure level that was
      increased throughout the experimental period. Oxygenation was significantly
      greater in animals ventilated with HFO compared with animals ventilated with CMV.
      The proportion of surfactant in large aggregate forms was significantly greater
      following ventilatory support with HFO compared with CMV. Surfactant aggregate
      conversion was also significantly lower during HFO compared with CMV. We conclude
      that in our model of acute lung injury, HFO was a superior mode of ventilation
      and reduced the conversion of alveolar surfactant large aggregates into small
      aggregate forms, resulting in a greater percentage of large aggregate forms in
      the alveolar space.

PMID- 11463595
TI  - Short-term effects of inhaled nitric oxide and prone position in pulmonary and
      extrapulmonary acute respiratory distress syndrome.
AB  - Inhaled nitric oxide (NO) and prone position (PP) are frequently used in the
      treatment of acute respiratory distress syndrome (ARDS). We compared the gas
      exchange and hemodynamic effects induced by the combination of NO inhalation and
      PP in patients with ARDS and analyzed whether or not pulmonary (Pu) and
      extrapulmonary (Epu) ARDS patients behave differently. Eight Pu and seven Epu
      ARDS patients were studied in four situations: supine position (SP); SP with NO
      inhalation at 5 ppm (SP + NO); PP; and PP with NO inhalation (PP + NO). In
      comparison with SP, NO inhalation and PP induced significant increases in
      Pa(O(2))/FI(O(2)) (from 106 +/- 58 in SP to 131 +/- 69 mm Hg in SP + NO, p =
      0.01, and to 184 +/- 67 mm Hg in PP, p < 0.001). Pu and Epu ARDS showed a similar
      improvement in Pa(O(2))/FI(O2) with PP. Only Pu ARDS patients showed a
      significant increase (p < 0.001) in oxygenation induced by NO inhalation from 81
      +/- 45 to 100 +/- 50 mm Hg in SP, and from 146 +/- 53 to 197 +/- 98 mm Hg in PP.
      In conclusion, PP is associated with a marked improvement in oxygenation,
      irrespective of the causes of ARDS, and additive effects of NO inhalation are
      mainly seen in patients with Pu ARDS.

PMID- 11463596
TI  - Upper airway sensation in snoring and obstructive sleep apnea.
AB  - Previous studies indicate that upper airway (UA) sensory receptors play a role in
      the maintenance of UA patency and contribute to arousal in response to airway
      occlusion. An impairment of UA sensory function could therefore predispose to UA
      obstruction during sleep. We hypothesized that UA sensation is impaired in
      obstructive sleep apnea (OSA), and that sensation improves after treatment with
      nasal continuous positive airway pressure (CPAP). We measured two-point
      discrimination (2PD) and vibratory sensation thresholds (VT) in 37 patients with
      OSA (mean [+/- SE] apnea- hypopnea index [AHI] = 39 +/- 5 events/h), 12 nonapneic
      snorers (SN), and 15 control subjects (CL). Sensory thresholds were determined in
      the UA and on the lip and hand as control sites. Both 2PD and VT were similar
      among the three groups at the lip and hand sites but were significantly reduced
      in the UA of OSA and SN subjects versus CL (p < 0.05). Values for 2PD and VT in
      the UA of OSA versus SN were not significantly different. Sensory measures were
      repeated after 6 mo in 23 OSA patients treated with CPAP as well as in 18
      untreated patients. Thresholds for 2PD and VT at control sites remained identical
      in both groups, as did 2PD for the UA. However, VT in the UA showed a significant
      improvement in treated (4.4 +/- 0.2 pre-CPAP versus 3.8 +/- 0.2 mm post-CPAP, p <
      0.05) but not untreated patients. These findings indicate the presence of a
      selective impairment in the detection of mechanical stimuli in the UA of patients
      with OSA and SN, which is partially reversible after treatment with nasal CPAP in
      patients with OSA.

PMID- 11463597
TI  - Bronchodilation and bronchoprotection in asthmatic preschool children from
      formoterol administered by mechanically actuated dry-powder inhaler and spacer.
AB  - We evaluated the bronchodilatory and the bronchoprotective effect of the long
      acting beta(2)-agonist formoterol administered as dry powder from a mechanically
      actuated dry-powder inhaler (DPI) using spacer in 12 asthmatic children 2 to 5 yr
      of age. Lung function was measured as the specific airway resistance (sRaw) in a
      whole body plethysmograph. Hyperventilation of cold, dry air was used as
      bronchial challenge, and the responsiveness was estimated as change in sRaw. The
      bronchoprotective effect of formoterol Turbohaler 9 microg was compared with
      salbutamol 200 microg and placebo at 15 min, 4 and 8 h postdose in a randomized,
      double-blind, placebo-controlled, crossover study. All treatments were
      administered from DPI (Turbohaler) actuated mechanically into a spacer.
      Formoterol and salbutamol caused similar and significant bronchodilation at the
      first measurement 3 min postdose. Formoterol offered a sustained and stable
      bronchodilation for at least 8 h. Salbutamol provided significant bronchodilation
      for less than 4 h. Formoterol caused significant bronchoprotection of 80% for at
      least 8 h compared with placebo, and from 4 h onward compared with salbutamol.
      Bronchoprotection from salbutamol lasted less than 4 h. In conclusion, formoterol
      administered as dry powder in a single dose provided rapid and sustained
      bronchodilation and clinically significant bronchoprotection for at least 8 h in
      2- to 5-yr-old asthmatic children. Furthermore, this study suggests that
      mechanical actuation of DPI using a spacer is effective for aerosol treatment of
      young asthmatic children.

PMID- 11463598
TI  - Heliox improves gas exchange during high-frequency ventilation in a pediatric
      model of acute lung injury.
AB  - Because heliox has a lower density as compared with air, we postulated that
      heliox would improve gas exchange during high-frequency oscillatory ventilation
      (HFOV) in a model of acute lung injury. In a prospective, cross-over trial, we
      studied 11 piglets with acute lung injury created by saline lavage. With initial
      conditions of permissive hypercapnia (Pa(CO(2)) 55-80 mm Hg), each piglet
      underwent HFOV with a fixed mean airway pressure, pressure oscillation, and
      ventilatory frequency. The following gas mixtures were used: oxygen-enriched air
      (60% O(2)/40% N(2)) and heliox (60% O(2)/ 40% He and 40% O(2)/60% He). Compared
      with oxygen-enriched air, the 40% and 60% helium gas mixtures reduced Pa(CO(2))
      by an average of 10.5 and 20.3 mm Hg, respectively. A modest improvement in
      oxygenation was seen with the 40% helium mixture. We conclude that heliox
      significantly improves carbon dioxide elimination and modestly improves
      oxygenation during HFOV in a model of acute lung injury. On the basis of test
      lung data and plethysmography measurements, we also conclude that heliox improves
      carbon dioxide elimination primarily through increased tidal volume delivery.
      Although heliox improved gas exchange during HFOV in our model, increased tidal
      volume delivery may limit clinical applicability.

PMID- 11463599
TI  - Differential mRNA expression of insulin-like growth factor-1 splice variants in
      patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.
AB  - Insulin-like growth factor-1 (IGF-1) is a highly mitogenic polypeptide detectable
      in human lung. Using competitive reverse transcriptase/polymerase chain reaction
      (RT-PCR), expression of four IGF-1 transcripts was examined in bronchoalveolar
      lavage cells (BALC) from normal subjects, idiopathic pulmonary fibrosis (IPF),
      stage I/II (no fibrosis), and stage III/IV (confirmed fibrosis) pulmonary
      sarcoidosis patients, and fibroblast strains isolated from normal and IPF lungs.
      Transcripts studied were Class 1 and Class 2 (exons 1 or 2, respectively) with
      IGF-1Eb or IGF-1Ea (exons 5 or 6, respectively). Total IGF-1 expression was
      downregulated in BALC of both patients with IPF (p < 0.01) and patients with
      sarcoidosis (p < 0.04) compared with healthy subjects. In contrast, both
      constitutive (p < 0.003) and transforming growth factor-beta (TGF-beta)- induced
      (p < 0.02) IGF-1 expression was higher in fibrotic, compared with normal,
      fibroblasts. These changes were associated with differential expression of IGF-1
      splice variants. Healthy subjects and sarcoidosis patients without fibrosis
      showed similar expression of Class 1/Class 2 and IGF-1Ea/IGF-1Eb. However,
      patients with fibrosis demonstrated discordant, increased relative abundance of
      Class 1 transcripts (p < 0.01). In parallel, all fibrosis patients failed to
      express Class 2, IGF-1Eb forms and sarcoidosis patients with fibrosis did not
      express the Class 1, IGF-1Eb variant either. Fibrotic fibroblasts expressed
      higher constitutive levels of Class 1, IGF-1Ea transcripts compared with normal
      fibroblasts. Class 2, IGF-1Eb forms were moderately expressed by fibroblasts only
      after stimulation with TGF-beta, which also further increased levels of Class 1,
      IGF-1Ea transcripts. Our findings suggest that transition from a healthy to a
      fibrotic phenotype occurs in association with a changing pattern of IGF-1 mRNA
      heterogeneity and leads us to hypothesize a potential role for specific IGF-1
      variants in fibrogenesis.

PMID- 11463600
TI  - Low-dose theophylline reduces eosinophilic inflammation but not exhaled nitric
      oxide in mild asthma.
AB  - Theophylline is well-established in the management of asthma, and there is some
      evidence of an antiinflammatory effect in asthma. It is not known whether
      theophylline affects inflammatory markers such as sputum eosinophils and exhaled
      nitric oxide (NO) in patients with mild asthma not receiving inhaled steroid
      therapy. In a double-blind, placebo-controlled, cross-over study of 15 patients
      with mild asthma, we assessed the effect of low-dose theophylline therapy (250 mg
      twice per day) on eosinophils in induced sputum, bronchoalveolar lavage (BAL) and
      airway biopsies at the end of both the treatment and placebo periods.
      Measurements of exhaled nitric oxide (NO) were made at the end of the active and
      placebo treatment periods of 5 wk each. Low-dose theophylline (mean serum level,
      6.1 mg/L) led to a significant reduction in mean (95% confidence interval [CI])
      sputum eosinophils from 11.3% (7.80-14.76%) to 8.0% (5.46-10.44%), BAL
      eosinophils from 3.4% (2.4-4.4%) to 1.7% (1.1-2.3%) and biopsy eosinophils from
      1.83% (0.76-2.89%) to 1.20% (0.27-2.13%) compared with placebo (all p < 0.05).
      There was no significant change in levels of exhaled NO or improvement in lung
      function and bronchial responsiveness. Low-dose theophylline induced
      antiinflammatory effects in asthma, reflected by a fall in airway eosinophils
      with no change in exhaled NO or changes in lung function.

PMID- 11463601
TI  - Elevated soluble ST2 protein levels in sera of patients with asthma with an acute
      exacerbation.
AB  - Previous studies have reported that ST2 is preferentially expressed on Th2 cells
      and plays a critical part in controlling airway inflammation in murine models of
      asthma. However, the clinical role of ST2 in patients with bronchial asthma
      remains unclear. In our study, we examined 56 patients with atopic asthma in a
      nonattack phase and 200 nonatopic normal volunteers for healthy control, and
      analyzed the relationship of their serum ST2 levels to asthma severity, pulmonary
      function, and laboratory data. Of the 56 patients with atopic asthma, 30
      exhibited asthmatic exacerbation, and their serum ST2 levels were also analyzed.
      The serum ST2 levels were low, but a statistical difference was found between
      patients with nonattack asthma and the healthy control group (p < 0.05). We also
      found a differential rise of serum ST2 level that correlates well with the
      severity of asthma exacerbation. Furthermore, the serum ST2 levels during asthma
      exacerbation statistically correlated with the percentage of predicted peak
      expiratory flow (r = -0.634, p = 0.004) and Pa(CO(2)) (r = 0.516, p = 0.003).
      These results suggest that soluble human ST2 protein in sera may be related to
      Th2-mediated allergic inflammation inducing acute exacerbation in patients with
      atopic asthma.

PMID- 11463602
TI  - Chronic hypoxia induces constitutive p38 mitogen-activated protein kinase
      activity that correlates with enhanced cellular proliferation in fibroblasts from
      rat pulmonary but not systemic arteries.
AB  - Pulmonary hypertension occurs commonly in patients with chronic hypoxic lung
      disease and is characterized by the remodeling of the pulmonary artery walls. The
      molecular mechanisms underlying such remodeling are unknown but we have recently
      shown that the stress-activated (Jnk and p38) mitogen-activated protein (MAP)
      kinases are activated in pulmonary artery fibroblasts following acute hypoxia. We
      now show that Erk and p38 MAP kinases are constitutively activated in fibroblasts
      derived from the remodeled pulmonary, but not the systemic circulation from rats
      exposed to chronically hypoxic conditions. Moreover, we find that such
      fibroblasts show sustained enhanced proliferative capacities relative to
      pulmonary artery fibroblasts derived from normoxic rats or to aortic fibroblasts
      from either normoxic or hypoxic rats. Finally, abrogation of p38, but not Erk MAP
      kinase activity by use of specific inhibitors, prevents the enhanced
      proliferative capacity exhibited by pulmonary artery fibroblasts. Taken together,
      these data suggest that enhanced p38 MAP kinase activity provides a molecular
      mechanism to explain the proliferation of pulmonary artery fibroblasts required
      for remodeling of the pulmonary vasculature.

PMID- 11463603
TI  - Extracellular superoxide dismutase attenuates lung injury after hemorrhage.
AB  - Reperfusion of the lung after hemorrhage generates free radicals such as
      superoxide (O(2)(.)) that may injure the lung; however, the relative importance
      of intracellular versus extracellular free radicals is unclear. The superoxide
      dismutases (SOD) are the primary enzymatic method to reduce superoxide. We
      examined whether lung-specific overexpression of extracellular superoxide
      dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wild-type mice
      and mice overexpressing the human EC-SOD gene with a lung-specific promoter were
      hemorrhaged by removing 30% of blood volume. After hemorrhage, the lung wet to
      dry weight ratios increased from 5.4 +/- 0.11 in unmanipulated control mice to
      6.3 +/- 0.16 in wild-type mice, but to only 5.60 +/- 0.17 in the EC-SOD
      transgenic mice (p < 0.05 compared with hemorrhaged wild-type). Hemorrhage
      induced lipid peroxidation, as assessed by lung F(2) isoprostanes, was lower in
      the EC-SOD transgenic mice (3.4 +/- 0.3 microg/lung) compared with wild-type mice
      (1.9 +/- 0.2 microg/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic
      mice had attenuated the hemorrhage-induced increase in both pulmonary nuclear
      factor kappa B (NK-kappaB) activation (relative absorbance 1.1 +/- 0.2 for EC-SOD
      transgenic versus 2.5 +/- 0.1 for wild-type; p < 0.05) and myeloperoxidase
      activity (5.1 +/- 0.87 units/g for EC-SOD transgenic versus 11.3 +/- 1.8 units/g
      for wild-type; p < 0.01). Thus, overexpression of pulmonary EC-SOD in the mouse
      lung attenuates lung injury after hemorrhage.

PMID- 11463604
TI  - Bronchoscopic volume reduction: a safe and effective alternative to surgical
      therapy for emphysema.
AB  - Lung volume reduction surgery (LVRS), the removal of damaged, hyperexpanded lung,
      has been shown to improve respiratory function in many patients with end-stage
      emphysema. We report the results of an animal study using a new
      transbronchoscopic alternative to LVRS in which a washout solution and fibrin
      based glue are used to collapse, seal, and scar target regions of abnormal lung.
      Twelve sheep had static and dynamic lung functions measured at baseline.
      Emphysema was produced by inhaled papain (7,000 U/wk x 4 wk), resulting in a
      significant increase of lung volumes, compliance, and airway resistance. The
      animals were then divided into three treatment groups of four animals, and
      underwent surgical volume reduction (SVR), bronchoscopic volume reduction (BVR),
      or bronchoscopy alone (Sham-BVR). Response to each intervention was assessed 8 to
      12 wk after treatment by measuring lung function and examining lung tissue. BVR
      and SVR groups responded with significant and similar decreases in TLC and
      residual volume (RV). Tissue examination demonstrated that BVR caused collapse of
      the lung with focal scarring in 11 of 20 target territories (55% success rate).
      Three of the 11 target zones developed sterile abscesses. Postprocedure
      complications were less frequent with BVR than with SVR. This pilot study
      suggests that lung volume reduction can be achieved in animals without surgery
      using a bronchoscopic approach and a novel fibrin-based glue system. BVR has the
      potential for simplifying volume reduction, extending indications, and reducing
      morbidity, mortality, and costs in humans.

PMID- 11463605
TI  - Effect of aerosolized uridine 5'-triphosphate on mucociliary clearance in mild
      chronic bronchitis.
AB  - Previous studies show that uridine 5'-triphosphate (UTP), a P2Y(2) receptor
      agonist, is effective at acutely enhancing mucociliary clearance in healthy,
      nonsmoking adults. UTP solution for inhalation is being developed by Inspire
      Pharmaceuticals under the compound number INS316. In a double-blind, randomized,
      crossover, placebo-controlled study we tested the single-dose effect of UTP in
      chronic smokers with mild chronic bronchitis (n = 15) by measuring the clearance
      of (99m)Tc-Fe(2)O(3) particles (4.0 microm mass median aerodynamic diameter
      [MMAD]) after inhalation of nebulized placebo (0.9% saline) and two doses of UTP
      (20 and 100 mg in the nebulizer). On each study day, gamma camera scanning was
      performed over a 2-h period. After an initial deposition scan, subjects inhaled
      placebo or UTP during the first 20 min of scanning. Analysis of whole lung
      clearance showed that the retention-time curves for each day were biphasic and
      that the earliest break point in the average curves occurred at 50 min. Mean
      particle clearance rate (Clr in %/min) through 50 min for placebo treatment was
      Clr = 0.65 +/- 0.27 whereas treatment with UTP showed Clr significantly increased
      to 0.95 +/- 0.48 and 0.93 +/- 0.44 for the 20-mg and 100-mg dose respectively, p
      < 0.005 for both as compared with placebo. These data show that mucociliary
      clearance associated with mild chronic bronchitis is acutely improved with
      minimal doses of aerosolized UTP, presumably because of its stimulation of
      ciliary beating and hydration of airway secretions.

PMID- 11463606
TI  - Sensory nerves promote ozone-induced lung inflammation in mice.
AB  - Genetically manipulated mice exhibiting altered innervation of the airways were
      used to examine the role of sensory nerves in ozone-induced lung inflammation.
      Transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara
      cell secretory protein (CCSP) promoter exhibit hyperinnervation of the airways by
      sympathetic and tachykinin-containing sensory nerve fibers. Mice carrying a
      mutation in the low-affinity NGF receptor (NGFR) gene possess deficits in sensory
      innervation. CCSP-NGF transgenic mice exhibited a twofold increase in the number
      of lung lavage neutrophil level whereas NGFR knockout mice exhibited a nearly 50%
      decrease in neutrophilic inflammation compared with wild-type mice 18 h after
      ozone inhalation. Treatment with neurokinin receptor antagonists reduced the
      level of neutrophilic inflammation in both wild-type and CCSP-NGF mice.
      Examination of lavage fluid cytokine concentrations revealed that 4 h after ozone
      exposure CCSP-NGF mice produced significantly higher amounts of the chemokine KC
      than wild-type mice exposed to ozone. The results of this study indicate that
      sensory nerves are important mediators of ozone-induced inflammation in mice.

PMID- 11463607
TI  - Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling.
AB  - Prostacyclin (PGI(2)) reduces pulmonary vascular resistance and attenuates
      vascular smooth muscle cell proliferation through signal transduction following
      ligand binding to its receptor. Because patients with severe pulmonary
      hypertension have a reduced PGI(2) receptor (PGI-R) expression in the remodeled
      pulmonary arterial smooth muscle, we hypothesized that pulmonary vascular
      remodeling may be modified PGI-R dependently. To test this hypothesis, PGI-R
      knockout (KO) and wild-type (WT) mice were subjected to a simulated altitude of
      17,000 ft or Denver altitude for 3 wk, and right ventricular pressure and lung
      histology were assessed. The PGI-R KO mice developed more severe pulmonary
      hypertension and vascular remodeling after chronic hypoxic exposure when compared
      to the WT mice. Our results indicate that PGI(2) and its receptor play an
      important role in the regulation of hypoxia-induced pulmonary vascular
      remodeling, and that the absence of a functional receptor worsens pulmonary
      hypertension.

PMID- 11463608
TI  - Plasma monocyte chemoattractant protein-1 and pulmonary vascular resistance in
      chronic thromboembolic pulmonary hypertension.
AB  - The pathogenesis of severe pulmonary hypertension seems to be related to
      inflammatory response in diseased sites. Monocyte chemoattractant protein-1 (MCP
      1) has been reported to play a role in the development of congestive heart
      failure. In this immunological response, activation and migration of leukocytes
      including macrophages to the inflammatory region are important factors. We
      hypothesized that the severity of pulmonary hypertension may be related to MCP-1,
      which is thought to be upregulated by blood pressure or shear stress in pulmonary
      vasculature as well as by immunological and inflammatory reactions in chronic
      thromboembolic pulmonary hypertension (CTEPH). Circulating levels of MCP-1,
      interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) were
      measured by sandwich ELISA in 14 patients with CTEPH. The plasma level of MCP-1
      was significantly correlated with pulmonary vascular resistance. In IL-1beta and
      TNF-alpha, on the other hand, there was no correlation between cytokines and
      pulmonary hemodynamics. Pathological specimens obtained from the patients with
      CTEPH undergoing thromboendarterectomy demonstrated immunoreactivity of MCP-1 in
      endothelium, smooth muscle cells, and macrophages within neointima in the
      hypertensive large elastic pulmonary artery. We conclude that MCP-1 is
      upregulated in the remodeling of pulmonary arteries in close association with
      increased pulmonary vascular resistance in CTEPH.

PMID- 11463609
TI  - Evolving concepts of the maturation of central pathways underlying the hypoxic
      ventilatory response.

PMID- 11463610
TI  - Sequence determination of reduction potentials by cysteinyl hydrogen bonds and
      peptide pipoles in [4Fe-4S] ferredoxins.
AB  - A sequence determinant of reduction potentials is reported for bacterial [4Fe-4S]
      type ferredoxins. The residue that is four residues C-terminal to the fourth
      ligand of either cluster is generally an alanine or a cysteine. In five
      experimental ferredoxin structures, the cysteine has the same structural
      orientation relative to the nearest cluster, which is stabilized by the SH...S
      bond. Although such bonds are generally considered weak, indications that Fe-S
      redox site sulfurs are better hydrogen-bond acceptors than most sulfurs include
      the numerous amide NH...S bonds noted by Adman and our quantum mechanical
      calculations. Furthermore, electrostatic potential calculations of 11
      experimental ferredoxin structures indicate that the extra cysteine decreases the
      reduction potential relative to an alanine by approximately 60 mV, in agreement
      with experimental mutational studies. Moreover, the decrease in potential is due
      to a shift in the polar backbone stabilized by the SH...S bond rather than to the
      slightly polar cysteinyl side chain. Thus, these cysteines can "tune" the
      reduction potential, which could optimize electron flow in an electron transport
      chain. More generally, hydrogen bonds involving sulfur can be important in
      protein structure/function, and mutations causing polar backbone shifts can alter
      electrostatics and thus affect redox properties or even enzymatic activity of a
      protein.

PMID- 11463611
TI  - Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and
      regulation of ion pumps in ventricular myocyte.
AB  - We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res
      1999, 84:571-586) by incorporating 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). The results
      indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and
      diffusion of CaATP may affect the amplitude and time course of intracellular
      Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio
      significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+),
      lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and
      decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during
      periodic voltage-clamp stimulation. The analysis suggests that the most important
      reason for these changes during metabolic inhibition is the down-regulation of
      the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High
      Ca(2+) concentrations developed near the membrane might have a greater influence
      on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+)
      concentrations in the bulk myoplasm. The model predictions are in general
      agreement with experimental observations measured under normal and pathological
      conditions.

PMID- 11463612
TI  - Molecular dynamics simulation of the human U2B" protein complex with U2 snRNA
      hairpin IV in aqueous solution.
AB  - A 2200-ps molecular dynamics (MD) simulation of the U2 snRNA hairpin IV/U2B"
      complex was performed in aqueous solution using the particle mesh Ewald method to
      consider long-range electrostatic interactions. To investigate the interaction
      and recognition process between the RNA and protein, the free energy
      contributions resulting from individual amino acids of the protein component of
      the RNA/protein complex were calculated using the recently developed glycine
      scanning method. The results revealed that the loop region of the U2 snRNA
      hairpin IV interacted mainly with three regions of the U2B" protein: 1) beta 1
      helix A, 2) beta 2-beta 3, and 3) beta 4-helix C. U2 snRNA hairpin IV bound U2B"
      in a similar orientation as that previously described for U1 snRNA with the U1A'
      protein; however, the details of the interaction differed in several aspects. In
      particular, beta 1-helix A and beta 4-helix C in U2B" were not observed to
      interact with RNA in the U1A' protein complex. Most of the polar and charged
      residues in the interacting regions had larger mutant free energies than the
      nonpolar residues, indicating that electrostatic interactions were important for
      stabilizing the RNA/protein complex. The interaction was further stabilized by a
      network of hydrogen bonds and salt bridges formed between RNA and protein that
      was maintained throughout the MD trajectory. In addition to the direct
      interactions between RNA and the protein, solvent-mediated interactions also
      contributed significantly to complex stability. A detailed analysis of the
      ordered water molecules in the hydration of the RNA/protein complex revealed that
      bridged water molecules reside at the interface of RNA and protein as long as
      2100 ps in the 2200-ps trajectory. At least 20 bridged water molecules, on
      average, contributed to the instantaneous stability of the RNA/protein complex.
      The stabilizing interaction energy due to bridging water molecules was obtained
      from ab initio Hartree-Fock and density functional theory calculations.

PMID- 11463613
TI  - Interactions of cholesterol with lipid bilayers: the preferred configuration and
      fluctuations.
AB  - The free energy difference associated with the transfer of a single cholesterol
      molecule from the aqueous phase into a lipid bilayer depends on its final
      location, namely on its insertion depth and orientation within the bilayer. We
      calculated desolvation and lipid bilayer perturbation contributions to the water
      to-membrane transfer free energy, thus allowing us to determine the most
      favorable location of cholesterol in the membrane and the extent of fluctuations
      around it. The electrostatic and nonpolar contributions to the solvation free
      energy were calculated using continuum solvent models. Lipid layer perturbations,
      resulting from both conformational restrictions of the lipid chains in the
      vicinity of the (rigid) cholesterol backbone and from cholesterol-induced elastic
      deformations, were calculated using a simple director model and elasticity
      theory, respectively. As expected from the amphipathic nature of cholesterol and
      in agreement with the available experimental data, our results show that at the
      energetically favorable state, cholesterol's hydrophobic core is buried within
      the hydrocarbon region of the bilayer. At this state, cholesterol spans
      approximately one leaflet of the membrane, with its OH group protruding into the
      polar (headgroup) region of the bilayer, thus avoiding an electrostatic
      desolvation penalty. We found that the transfer of cholesterol into a membrane is
      mainly driven by the favorable nonpolar contributions to the solvation free
      energy, whereas only a small opposing contribution is caused by conformational
      restrictions of the lipid chains. Our calculations also predict a strong tendency
      of the lipid layer to elastically respond to (thermally excited) vertical
      fluctuations of cholesterol so as to fully match the hydrophobic height of the
      solute. However, orientational fluctuations of cholesterol were found to be
      accompanied by both an elastic adjustment of the surrounding lipids and by a
      partial exposure of the hydrophobic cholesterol backbone to the polar (headgroup)
      environment. Our calculations of the molecular order parameter, which reflects
      the extent of orientational fluctuations of cholesterol in the membrane, are in
      good agreement with available experimental data.

PMID- 11463614
TI  - Polymer-induced membrane contraction, phase separation, and fusion via Marangoni
      flow.
AB  - Experiments have shown that the depletion of polymer in the region between two
      apposed (contacting or nearly contacting) bilayer membranes leads to fusion. In
      this paper we show theoretically that the addition of nonadsorbing polymer in
      solution can promote lateral contraction and phase separation of the lipids in
      the outer monolayers of the membranes exposed to the polymer solution, i.e.,
      outside the contact zone. This initial phase coexistence of higher- and lower
      density lipid domains in the outer monolayer results in surface tension gradients
      in the outer monolayer. Initially, the inner layer lipids are not exposed to the
      polymer solution and remain in their original "unstressed" state. The
      differential stresses on the bilayers give rise to a Marangoni flow of lipid from
      the outer monolayers in the "contact zone" (where there is little polymer and
      hence a uniform phase) to the outer monolayers in the "reservoir" (where
      initially the surface tension gradients are large due to the polymer-induced
      phase separation). As a result, the low-density domains of the outer monolayers
      in the contact zone expose their hydrophobic chains, and those of the inner
      monolayers, to the solvent and to each other across the narrow water gap,
      allowing fusion to occur via a hydrophobic interaction. More generally, this type
      of mechanism suggests that fusion and other intermembrane interactions may be
      triggered by Marangoni flows induced by surface tension gradients that provide
      "action at a distance" far from the fusion or interaction zone.

PMID- 11463615
TI  - Thermodynamics and kinetics of actin filament nucleation.
AB  - We have performed computer simulations and free energy calculations to determine
      the thermodynamics and kinetics of actin nucleation and thus identify a probable
      nucleation pathway and critical nucleus size. The binding free energies of
      structures along the nucleation pathway are found through a combination of
      electrostatic calculations and estimates of the entropic and surface area
      contributions. The association kinetics for the formation of each structure are
      determined through a series of Brownian dynamics simulations. The combination of
      the binding free energies and the association rate constants determines the
      dissociation rate constants, allowing for a complete characterization of the
      nucleation and polymerization kinetics. The results indicate that the trimer is
      the size of the critical nucleus, and the rate constants produce polymerization
      plots that agree very well with experimental results over a range of actin
      monomer concentrations.

PMID- 11463616
TI  - Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I.
      Krogh's model.
AB  - Human bone marrow (BM) is a tissue of complex architectural organization, which
      includes granulopoietic loci, erythroblastic islets, and lymphocytic nodules.
      Oxygen tension (pO(2)) is an important determinant of hematopoietic stem and
      progenitor cell proliferation and differentiation. Thus, understanding the impact
      of the BM architectural organization on pO(2) levels in extravascular
      hematopoietic tissue is an important biophysical problem. However, currently it
      is impossible to measure pO(2) levels and their spatial variations in the BM.
      Homogeneous Kroghian models were used to estimate pO(2) distribution in the BM
      hematopoietic compartment (BMHC) and to conservatively simulate pO(2)-limited
      cellular architectures. Based on biophysical data of hematopoietic cells and
      characteristics of BM physiology, we constructed a tissue cylinder solely
      occupied by granulocytic progenitors (the most metabolically active stage of the
      most abundant cell type) to provide a physiologically relevant limiting case.
      Although the number of possible cellular architectures is large, all simulated
      pO(2) profiles fall between two extreme cases: those of homogeneous tissues with
      adipocytes and granulocytic progenitors, respectively. This was illustrated by
      results obtained from a parametric criterion derived for pO(2) depletion in the
      extravascular tissue. Modeling results suggest that stem and progenitor cells
      experience a low pO(2) environment in the BMHC.

PMID- 11463617
TI  - Modeling pO(2) distributions in the bone marrow hematopoietic compartment. II.
      Modified Kroghian models.
AB  - Hematopoietic cells of various lineages are organized in distinct cellular
      architectures in the bone marrow hematopoietic compartment (BMHC). The
      homogeneous Kroghian model, which deals only with a single cell type, may not be
      sufficient to accurately describe oxygen transfer in the BMHC. Thus, for cellular
      architectures of physiological significance, more complex biophysical-transport
      models were considered and compared against simulations using the homogeneous
      Kroghian model. The effects of the heterogeneity of model parameters on the
      oxygen tension (pO(2)) distribution were examined using the multilayer Kroghian
      model. We have also developed two-dimensional Kroghian models to simulate several
      cellular architectures in which a cell cluster (erythroid cluster) or an
      individual cell (megakaryocyte or adipocyte) is located in the BMHC predominantly
      occupied by mature granulocytes. pO(2) distributions in colony-type cellular
      arrangements (erythroblastic islets, granulopoietic loci, and lymphocytic
      nodules) in the BMHC were also evaluated by modifying the multilayer Kroghian
      model. The simulated results indicate that most hematopoietic progenitors
      experience low pO(2) values, which agrees with the finding that low pO(2)
      promotes the expansion of various hematopoietic progenitors. These results
      suggest that the most primitive stem cells, which are located even further away
      from BM sinuses, are likely located in a very low pO(2) environment.

PMID- 11463618
TI  - Probing the origins of increased activity of the E22Q "Dutch" mutant Alzheimer's
      beta-amyloid peptide.
AB  - The amyloid peptide congener A beta(10--35)-NH(2) is simulated in an aqueous
      environment in both the wild type (WT) and E22Q "Dutch" mutant forms. The origin
      of the noted increase in deposition activity resulting from the Dutch mutation is
      investigated. Multiple nanosecond time scale molecular dynamics trajectories were
      performed and analyzed using a variety of measures of the peptide's average
      structure, hydration, conformational fluctuations, and dynamics. The results of
      the study support the conclusions that 1) the E22Q mutant and WT peptide are both
      stable in "collapsed coil" conformations consistent with the WT structure of, J.
      Struct. Biol. 130:130--141); 2) the E22Q peptide is more flexible in solution,
      supporting early claims that its equilibrium structural fluctuations are larger
      than those of the WT peptide; and 3) the local E22Q mutation leads to a change in
      the first solvation layer in the region of the peptide's "hydrophobic patch,"
      resulting in a more hydrophobic solvation of the mutant peptide. The simulation
      results support the view that the noted increase in activity due to the Dutch
      mutation results from an enhancement of the desolvation process that is an
      essential step in the aggregation of the peptide.

PMID- 11463619
TI  - Heat capacity of protein folding.
AB  - We construct a Hamiltonian for a single domain protein where the contact enthalpy
      and the chain entropy decrease linearly with the number of native contacts. The
      hydration effect upon protein unfolding is included by modeling water as ideal
      dipoles that are ordered around the unfolded surfaces, where the influence of
      these surfaces, covered with an "ice-like" shell of water, is represented by an
      effective field that directs the water dipoles. An intermolecular pair
      interaction between water molecules is also introduced. The heat capacity of the
      model exhibits, the common feature of small globular proteins, two peaks
      corresponding to cold and warm unfolding, respectively. By introducing ad hoc
      vibrational modes, we obtain quantitatively good accordance with experiments on
      myoglobin.

PMID- 11463620
TI  - Analysis of a 10-ns molecular dynamics simulation of mouse acetylcholinesterase.
AB  - A 10-ns molecular dynamics simulation of mouse acetylcholinesterase was analyzed,
      with special attention paid to the fluctuation in the width of the gorge and
      opening events of the back door. The trajectory was first verified to ensure its
      stability. We defined the gorge proper radius as the measure for the extent of
      gorge opening. We developed an expression of an inter-atom distance
      representative of the gorge proper radius in terms of projections on the
      principal components. This revealed the fact that collective motions of many
      scales contribute to the opening behavior of the gorge. Covariance and
      correlation results identified the motions of the protein backbone as the gorge
      opens. In the back-door region, side-chain dihedral angles that define the
      opening were identified.

PMID- 11463621
TI  - Mesoscopic simulation of cell membrane damage, morphology change and rupture by
      nonionic surfactants.
AB  - A new simulation method, dissipative particle dynamics, is applied to model
      biological membranes. In this method, several atoms are united into a single
      simulation particle. The solubility and compressibility of the various liquid
      components are reproduced by the simulation model. When applied to a bilayer of
      phosphatidylethanolamine, the membrane structure obtained matches quantitatively
      with full atomistic simulations and with experiments reported in the literature.
      The method is applied to investigate the cause of cell death when bacteria are
      exposed to nonionic surfactants. Mixed bilayers of lipid and nonionic surfactant
      were studied, and the diffusion of water through the bilayer was monitored. Small
      transient holes are seen to appear at 40% mole-fraction C(9)E(8), which become
      permanent holes between 60 and 70% surfactant. When C(12)E(6) is applied,
      permanent holes only arise at 90% mole-fraction surfactant. Some simulations have
      been carried out to determine the rupture properties of mixed bilayers of
      phosphatidylethanolamine and C(12)E(6). These simulations indicate that the area
      of a pure lipid bilayer can be increased by a factor 2. The inclusion of
      surfactant considerably reduces both the extensibility and the maximum stress
      that the bilayer can withstand. This may explain why dividing cells are more at
      risk than static cells.

PMID- 11463622
TI  - Free energy decomposition of protein-protein interactions.
AB  - A free energy decomposition scheme has been developed and tested on antibody
      antigen and protease-inhibitor binding for which accurate experimental structures
      were available for both free and bound proteins. Using the x-ray coordinates of
      the free and bound proteins, the absolute binding free energy was computed
      assuming additivity of three well-defined, physical processes: desolvation of the
      x-ray structures, isomerization of the x-ray conformation to a nearby local
      minimum in the gas-phase, and subsequent noncovalent complex formation in the gas
      phase. This free energy scheme, together with the Generalized Born model for
      computing the electrostatic solvation free energy, yielded binding free energies
      in remarkable agreement with experimental data. Two assumptions commonly used in
      theoretical treatments; viz., the rigid-binding approximation (which assumes no
      conformational change upon complexation) and the neglect of vdW interactions,
      were found to yield large errors in the binding free energy. Protein-protein vdW
      and electrostatic interactions between complementary surfaces over a relatively
      large area (1400--1700 A(2)) were found to drive antibody-antigen and protease
      inhibitor binding.

PMID- 11463623
TI  - Are proteins well-packed?
AB  - The average packing density inside proteins is as high as in crystalline solids.
      Does this mean proteins are well-packed? We go beyond average densities, and look
      at the full distribution functions of free volumes inside proteins. Using a new
      and rigorous Delaunay triangulation method for parsing space into empty and
      filled regions, we introduce formal definitions of interior and surface packing
      densities. Although proteins look like organic crystals by the criterion of
      average density, they look more like liquids and glasses by the criterion of
      their free volume distributions. The distributions are broad, and the scalings of
      volume-to-surface, volume-to-cluster-radius, and numbers of void versus volume
      show that the interiors of proteins are more like randomly packed spheres near
      their percolation threshold than like jigsaw puzzles. We find that larger
      proteins are packed more loosely than smaller proteins. And we find that the
      enthalpies of folding (per amino acid) are independent of the packing density of
      a protein, indicating that van der Waals interactions are not a dominant
      component of the folding forces.

PMID- 11463624
TI  - The optical stretcher: a novel laser tool to micromanipulate cells.
AB  - When a dielectric object is placed between two opposed, nonfocused laser beams,
      the total force acting on the object is zero but the surface forces are additive,
      thus leading to a stretching of the object along the axis of the beams. Using
      this principle, we have constructed a device, called an optical stretcher, that
      can be used to measure the viscoelastic properties of dielectric materials,
      including biologic materials such as cells, with the sensitivity necessary to
      distinguish even between different individual cytoskeletal phenotypes. We have
      successfully used the optical stretcher to deform human erythrocytes and mouse
      fibroblasts. In the optical stretcher, no focusing is required, thus radiation
      damage is minimized and the surface forces are not limited by the light power.
      The magnitude of the deforming forces in the optical stretcher thus bridges the
      gap between optical tweezers and atomic force microscopy for the study of
      biologic materials.

PMID- 11463625
TI  - Dynamic regulation of sarcoplasmic reticulum Ca(2+) content and release by
      luminal Ca(2+)-sensitive leak in rat ventricular myocytes.
AB  - In cardiac muscle, excitation-contraction (E-C) coupling is determined by the
      ability of the sarcoplasmic reticulum (SR) to store and release Ca(2+). It has
      been hypothesized that the Ca(2+) sequestration and release mechanisms might be
      functionally linked to optimize the E-C coupling process. To explore the
      relationships between the loading status of the SR and functional state of the
      Ca(2+) release mechanism, we examined the effects of changes in SR Ca(2+) content
      on spontaneous Ca(2+) sparks in saponin-permeabilized and patch-clamped rat
      ventricular myocytes. SR Ca(2+) content was manipulated by pharmacologically
      altering the capacities of either Ca(2+) uptake or leak. Ca(2+) sparks were
      recorded using a confocal microscope and Fluo-3 and were quantified considering
      missed events. SR Ca(2+) content was assessed by application of caffeine.
      Exposure of permeabilized cells to anti-phospholamban antibodies elevated the SR
      Ca(2+) content and increased the frequency of sparks. Suppression of the SR
      Ca(2+) pump by thapsigargin lowered [Ca(2+)](SR) and reduced the frequency of
      sparks. The ryanodine receptor (RyR) blockers tetracaine and Mg(2+) transiently
      suppressed the frequency of sparks. Upon washout of the drugs, sparking activity
      transiently overshot control levels. Low doses of caffeine transiently
      potentiated sparking activity upon application and transiently depressed the
      sparks upon removal. In patch-clamped cardiac myocytes, exposure to caffeine
      produced only a transient increase in the probability of sparks induced by
      depolarization. We interpret these results in terms of a novel dynamic control
      scheme for SR Ca(2+) cycling. A central element of this scheme is a luminal
      Ca(2+) sensor that links the functional activity of RyRs to the loading state of
      the SR, allowing cells to auto-regulate the size and functional state of their SR
      Ca(2+) pool. These results are important for understanding the regulation of
      intracellular Ca(2+) release and contractility in cardiac muscle.

PMID- 11463626
TI  - Multiparticle adhesive dynamics. Interactions between stably rolling cells.
AB  - A novel numerical simulation of adhesive particles (cells) reversibly interacting
      with an adhesive surface under flow is presented. Particle--particle and particle
      -wall hydrodynamic interactions in low Reynolds number Couette flow are
      calculated using a boundary element method that solves an integral representation
      of the Stokes equation. Molecular bonds between surfaces are modeled as linear
      springs and stochastically formed and broken according to postulated descriptions
      of force-dependent kinetics. The resulting simulation, Multiparticle Adhesive
      Dynamics, is applied to the problem of selectin-mediated rolling of hard spheres
      coated with leukocyte adhesion molecules (cell-free system). Simulation results
      are compared to flow chamber experiments performed with carbohydrate-coated
      spherical beads rolling on P-selectin. Good agreement is found between theory and
      experiment, with the main observation being a decrease in rolling velocity with
      increasing concentration of rolling cells or increasing proximity between rolling
      cells. Pause times are found to increase and deviation motion is found to
      decrease as pairs of rolling cells become closer together or align with the flow.

PMID- 11463627
TI  - U-type inactivation of Kv3.1 and Shaker potassium channels.
AB  - We previously concluded that the Kv2.1 K(+) channel inactivates preferentially
      from partially activated closed states. We report here that the Kv3.1 channel
      also exhibits two key features of this inactivation mechanism: a U-shaped voltage
      dependence measured at 10 s and stronger inactivation with repetitive pulses than
      with a single long depolarization. More surprisingly, slow inactivation of the
      Kv1 Shaker K(+) channel (Shaker B Delta 6--46) also has a U-shaped voltage
      dependence for 10-s depolarizations. The time and voltage dependence of recovery
      from inactivation reveals two distinct components for Shaker. Strong
      depolarizations favor inactivation that is reduced by K(o)(+) or by partial block
      by TEA(o), as previously reported for slow inactivation of Shaker. However,
      depolarizations near 0 mV favor inactivation that recovers rapidly, with strong
      voltage dependence (as for Kv2.1 and 3.1). The fraction of channels that recover
      rapidly is increased in TEA(o) or high K(o)(+). We introduce the term U-type
      inactivation for the mechanism that is dominant in Kv2.1 and Kv3.1. U-type
      inactivation also makes a major but previously unrecognized contribution to slow
      inactivation of Shaker.

PMID- 11463628
TI  - Voltage-dependent formation of gramicidin channels in lipid bilayers.
AB  - The formation kinetics of gramicidin A channels in lipid bilayer membranes has
      been characterized as a function of voltage for different solution conditions and
      membrane composition. The frequency of channel events was measured during the
      application of voltage ramps and counted in given intervals, a procedure that
      eliminated the effects of drift in gramicidin concentration. The formation rate
      was found to increase strongly with voltages up to approximately 50 mV and then
      to level off slightly. The shape of the voltage dependence was independent of
      lipid solvent and ramp speed but differed for different ions and different
      solution concentrations. This suggested an ion occupancy effect on the formation
      rate that was further supported by the fact that the minimum of the formation
      rate was shifted toward the equilibrium potential in asymmetric solution
      concentrations. The effects are explained in terms of a model that contains two
      contributions to the voltage dependence, a voltage-dependent ion binding to the
      monomers and a polarization of monomers by the applied electric field and by the
      occupied ions. The theory is found to give a good fit to experimental data.

PMID- 11463629
TI  - cAmp activation of apical membrane Cl(-) channels: theoretical considerations for
      impedance analysis.
AB  - Transepithelial electrical impedance analysis provides a sensitive method to
      evaluate the conductances and capacitances of apical and basolateral plasma
      membranes of epithelial cells. Impedance analysis is complicated, due not only to
      the anatomical arrangement of the cells and their paracellular shunt pathways,
      but also in particular to the existence of audio frequency-dependent capacitances
      or dispersions. In this paper we explore implications and consequences of
      anatomically related Maxwell-Wagner and Cole-Cole dielectric dispersions that
      impose limitations, approximations, and pitfalls of impedance analysis when
      tissues are studied under widely ranging spontaneous rates of transport, and in
      particular when apical membrane sodium and chloride channels are activated by
      adenosine 3',5'-cyclic monophosphate (cAMP) in A6 epithelia. We develop the
      thesis that capacitive relaxation processes of any origin lead not only to
      dependence on frequency of the impedance locus, but also to the appearance of
      depressed semicircles in Nyquist transepithelial impedance plots, regardless of
      the tightness or leakiness of the paracellular shunt pathways. Frequency
      dependence of capacitance precludes analysis of data in traditional ways, where
      capacitance is assumed constant, and is especially important when apical and/or
      basolateral membranes exhibit one or more dielectric dispersions.

PMID- 11463630
TI  - PGE(2) activation of apical membrane Cl(-) channels in A6 epithelia: impedance
      analysis.
AB  - Measurements of transepithelial electrical impedance of continuously short
      circuited A6 epithelia were made at audio frequencies (0.244 Hz to 10.45 kHz) to
      investigate the time course and extent to which prostaglandin E(2) (PGE(2))
      modulates Cl(-) transport and apical membrane capacitance in this cell-cultured
      model epithelium. Apical and basolateral membrane resistances were determined by
      nonlinear curve-fitting of the impedance vectors at relatively low frequencies
      (<50 Hz) to equations (Paunescu, T. G., and S. I. Helman. 2001. Biophys. J.
      81:838--851) where depressed Nyquist impedance semicircles were characteristic of
      the membrane impedances under control Na(+)-transporting and amiloride-inhibited
      conditions. In all tissues (control, amiloride-blocked, and amiloride-blocked and
      furosemide-pretreated), PGE(2) caused relatively small (< approximately 3
      microA/cm(2)) and rapid (<60 s) maximal increase of chloride current due to
      activation of a rather large increase of apical membrane conductance that
      preceded significant activation of Na(+) transport through amiloride-sensitive
      epithelial Na(+) channels (ENaCs). Apical membrane capacitance was frequency
      dependent with a Cole-Cole dielectric dispersion whose relaxation frequency was
      near 150 Hz. Analysis of the time-dependent changes of the complex frequency
      dependent equivalent capacitance of the cells at frequencies >1.5 kHz revealed
      that the mean 9.8% increase of capacitance caused by PGE(2) was not correlated in
      time with activation of chloride conductance, but rather correlated with
      activation of apical membrane Na(+) transport.

PMID- 11463631
TI  - Kv4 channels exhibit modulation of closed-state inactivation in inside-out
      patches.
AB  - The mechanisms of inactivation gating of the neuronal somatodendritic A-type K(+)
      current and the cardiac I(to) were investigated in Xenopus oocyte macropatches
      expressing Kv4.1 and Kv4.3 channels. Upon membrane patch excision (inside-out),
      Kv4.1 channels undergo time-dependent acceleration of macroscopic inactivation
      accompanied by a parallel partial current rundown. These changes are readily
      reversible by patch cramming, suggesting the influence of modulatory cytoplasmic
      factors. The consequences of these perturbations were investigated in detail to
      gain insights into the biophysical basis and mechanisms of inactivation gating.
      Accelerated inactivation at positive voltages (0 to +110 mV) is mainly the result
      of reducing the time constant of slow inactivation and the relative weight of the
      slow component of inactivation. Concomitantly, the time constants of closed-state
      inactivation at negative membrane potentials (-90 to -50 mV) are substantially
      decreased in inside-out patches. Deactivation is moderately accelerated, and
      recovery from inactivation and the peak G--V curve exhibit little or no change.
      In agreement with more favorable closed-state inactivation in inside-out patches,
      the steady-state inactivation curve exhibits a hyperpolarizing shift of
      approximately 10 mV. Closed-state inactivation was similarly enhanced in Kv4.3.
      An allosteric model that assumes significant closed-state inactivation at all
      relevant voltages can explain Kv4 inactivation gating and the modulatory changes.

PMID- 11463632
TI  - Locating phospholamban in co-crystals with Ca(2+)-ATPase by cryoelectron
      microscopy.
AB  - Phospholamban (PLB) is responsible for regulating Ca(2+) transport by Ca(2+)
      ATPase across the sarcoplasmic reticulum of cardiac and smooth muscle. This
      regulation is coupled to beta-adrenergic stimulation, and dysfunction has been
      associated with end-stage heart failure. PLB appears to directly bind to Ca(2+)
      ATPase, thus slowing certain steps in the Ca(2+) transport cycle. We have
      determined 3D structures from co-crystals of PLB with Ca(2+)-ATPase by
      cryoelectron microscopy of tubular co-crystals at 8--10 A resolution.
      Specifically, we have used wild-type PLB, a monomeric PLB mutant (L37A), and a
      pentameric PLB mutant (N27A) for co-reconstitution and have compared resulting
      structures with three control structures of Ca(2+)-ATPase alone. The overall
      molecular shape of Ca(2+)-ATPase was indistinguishable in the various
      reconstructions, indicating that PLB did not have any global effects on Ca(2+)
      ATPase conformation. Difference maps reveal densities which we attributed to the
      cytoplasmic domain of PLB, though no difference densities were seen for PLB's
      transmembrane helix. Based on these difference maps, we propose that a single PLB
      molecule interacts with two Ca(2+)-ATPase molecules. Our model suggests that PLB
      may resist the large domain movements associated with the catalytic cycle, thus
      inhibiting turnover.

PMID- 11463633
TI  - A model for 4-aminopyridine action on K channels: similarities to
      tetraethylammonium ion action.
AB  - We present a model for the action of 4-aminopyridine (4AP) on K channels. The
      model is closely based on the gating current studies of the preceding paper and
      has been extended to account for ionic current data in the literature. We propose
      that 4AP, like tetraethylammonium ion and other quaternary ammonium ions, enters
      and leaves the channel only when the activation gate is open, a proposal that is
      strongly supported by the literature. Once in the open channel, 4AP's major
      action is to bias the activation gate toward the closed conformation by
      approximately the energy of a hydrogen bond. S4 segment movement, as reflected in
      gating currents, is almost normal for a 4AP-occupied channel; only the final
      opening transition is affected. The model is qualitatively the same as the one
      used for many years to explain the action of quaternary ammonium ions.

PMID- 11463634
TI  - Resolving the gating charge movement associated with late transitions in K
      channel activation.
AB  - We examined the late transitions in the activation sequence of potassium channels
      by analyzing gating currents of mutant Shaker IR channels and using the potassium
      channel blocker 4-aminopyridine (4AP). Gating currents were recorded from a
      double mutant of Shaker that was nonconducting (W434F mutation) and had the late
      gating transitions shifted to the right on the voltage axis (L382C mutation),
      thus separating the late transitions from the early ones. 4AP applied to the
      double mutant blocked the final transition and made possible novel observations
      of the isolated intermediate transitions, the ones that immediately precede the
      final opening of the channel. These transitions, which have not been well
      characterized previously, produce a distinct fast component in the gating current
      tails. Two intermediate transitions contribute to the fast component and carry
      23% of the total gating charge. The effect of 4AP is well modeled as a selective
      block of the final gating transition, which opens the channel. The final
      transition contributes approximately 5% of the total gating charge.

PMID- 11463635
TI  - Structural models of the MscL gating mechanism.
AB  - Three-dimensional structural models of the mechanosensitive channel of large
      conductance, MscL, from the bacteria Mycobacterium tuberculosis and Escherichia
      coli were developed for closed, intermediate, and open conformations. The
      modeling began with the crystal structure of M. tuberculosis MscL, a homopentamer
      with two transmembrane alpha-helices, M1 and M2, per subunit. The first 12 N
      terminal residues, not resolved in the crystal structure, were modeled as an
      amphipathic alpha-helix, called S1. A bundle of five parallel S1 helices are
      postulated to form a cytoplasmic gate. As membrane tension induces expansion, the
      tilts of M1 and M2 are postulated to increase as they move away from the axis of
      the pore. Substantial expansion is postulated to occur before the increased
      stress in the S1 to M1 linkers pulls the S1 bundle apart. During the opening
      transition, the S1 helices and C-terminus amphipathic alpha-helices, S3, are
      postulated to dock parallel to the membrane surface on the perimeter of the
      complex. The proposed gating mechanism reveals critical spatial relationships
      between the expandable transmembrane barrel formed by M1 and M2, the gate formed
      by S1 helices, and "strings" that link S1s to M1s. These models are consistent
      with numerous experimental results and modeling criteria.

PMID- 11463636
TI  - Robust, high-resolution, whole cell patch-clamp capacitance measurements using
      square wave stimulation.
AB  - High-resolution, whole cell capacitance measurements are usually performed using
      sine wave stimulation using a single frequency or a sum of two frequencies. We
      present here a high-resolution technique for whole-cell capacitance measurements
      based on square-wave stimulation. The square wave represents a sum of sinusoidal
      frequencies at odd harmonics of the base frequency, the amplitude of which is
      highest for the base frequency and decreases as the frequency increases. The
      resulting currents can be analyzed by fitting the current relaxations with
      exponentials, or by a phase-sensitive detector technique. This method provides a
      resolution undistinguishable from that of single-frequency sine wave stimulation,
      and allows for clear separation of changes in capacitance, membrane conductance,
      and access resistance. In addition, it allows for the analysis of more complex
      equivalent circuits as associated with the presence of narrow fusion pores during
      degranulation, tracking many equivalent circuit parameters simultaneously. The
      method is insensitive to changes in the reversal potential, pipette capacitance,
      or widely varying cell circuit parameters. It thus provides important advantages
      in terms of robustness for measuring cell capacitances, and allows analysis of
      complicated changes of the equivalent circuits.

PMID- 11463637
TI  - Osmotically induced membrane tension modulates membrane permeabilization by class
      L amphipathic helical peptides: nucleation model of defect formation.
AB  - The mechanism of action of lytic peptides on membranes is widely studied and is
      important in view of potential medical applications. Previously (I. V. Polozov,
      A. I. Polozova, E. M. Tytler, G. M. Anantharamaiah, J. P. Segrest, G. A. Woolley,
      and R. M., Biochemistry, 36:9237--9245) we analyzed the mechanism of membrane
      permeabilization by 18L, the archetype lytic peptide featuring the class L
      amphipathic alpha-helix, according to the classification of Segrest et al. (J. P.
      Segrest, G. de Loof, J. G. Dohlman, C. G. Brouillette, and G. M. Anantharamaiah,
      1990, Proteins, 8:103--117). We concluded that the 18L peptide destabilizes
      membranes, leading to a transient formation of large defects that result in
      contents leakage and, in the presence of bilayer-bilayer contact, could lead to
      vesicle fusion. Here we report that this defect formation is strongly enhanced by
      the membrane tension induced by osmotic swelling of vesicles. Even below standard
      leakage-inducing peptide/lipid ratios, membrane resistance to osmotic tension
      drops from hundreds to tens of milliosmoles. The actual decrease is dependent on
      the peptide/lipid ratio and on the type of lipid. We propose that under membrane
      tension a peptidic pore serves as a nucleation site for the transient formation
      of a lipidic pore. The tension is released upon pore expansion with inclusion of
      more peptides and lipids into the pore lining. This tension modulation of leakage
      was observed for other class L peptides (mastoparan, K18L) and thus may be of
      general applicability for the action of membrane active lytic peptides.

PMID- 11463638
TI  - Asymmetric pore distribution and loss of membrane lipid in electroporated DOPC
      vesicles.
AB  - An externally applied electric field across vesicles leads to transient
      perforation of the membrane. The distribution and lifetime of these pores was
      examined using 1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC) phospholipid
      vesicles using a standard fluorescent microscope. The vesicle membrane was
      stained with a fluorescent membrane dye, and upon field application, a single
      membrane pore as large as approximately 7 microm in diameter was observed at the
      vesicle membrane facing the negative electrode. At the anode-facing hemisphere,
      large and visible pores are seldom found, but formation of many small pores is
      implicated by the data. Analysis of pre- and post-field fluorescent vesicle
      images, as well as images from negatively stained electron micrographs, indicate
      that pore formation is associated with a partial loss of the phospholipid bilayer
      from the vesicle membrane. Up to approximately 14% of the membrane surface could
      be lost due to pore formation. Interestingly, despite a clear difference in the
      size distribution of the pores observed, the effective porous areas at both
      hemispheres was approximately equal. Ca(2+) influx measurements into perforated
      vesicles further showed that pores are essentially resealed within approximately
      165 ms after the pulse. The pore distribution found in this study is in line with
      an earlier hypothesis (E. Tekle, R. D. Astumian, and P. B. Chock, 1994, Proc.
      Natl. Acad. Sci. U.S.A. 91:11512--11516) of asymmetric pore distribution based on
      selective transport of various fluorescent markers across electroporated
      membranes.

PMID- 11463639
TI  - Dehydration induces lateral expansion of polyunsaturated 18:0-22:6
      phosphatidylcholine in a new lamellar phase.
AB  - To gain a better understanding of the biological role of polyunsaturated
      phospholipids, infrared (IR) linear dichroism, NMR, and x-ray diffraction studies
      have been conducted on the lyotropic phase behavior and bilayer dimensions of sn
      1 chain perdeuterated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine
      (SDPC-d35), a mixed-chain saturated (18:0)-polyunsaturated (22:6 omega 3) lipid.
      SDPC films were hydrated at definite values of temperature (T) and relative
      humidity (RH). In excess water, the lipid forms exclusively lamellar phases in
      the temperature range 0--50 degrees C. Upon dehydration the lipid undergoes the
      main phase transition between the liquid-crystalline (L(alpha)) and gel (L(beta))
      phase at T < 15 degrees C. Both the saturated and polyunsaturated chains adopt a
      stretched conformation in the L(beta) phase, presumably the all-trans (stearoyl)
      and angle iron or helical (docosahexaenoyl) one. A new fluid lamellar phase
      (L(alpha)') was found in partially hydrated samples at T > 15 degrees C. SDPC
      membranes expand laterally and contract vertically in the L(alpha)' phase when
      water was removed. This tendency is in sharp contrast to typical dehydration
      induced changes of membrane dimensions. The slope of the phase transition lines
      in the RH-T phase diagram reveal that the lyotropic L(alpha)'-L(alpha) and
      L(beta)-L(alpha) transitions are driven by enthalpy and entropy, respectively The
      possible molecular origin of the phase transitions is discussed. The properties
      of SDPC are compared with that of membranes of monounsaturated 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC-d31).

PMID- 11463640
TI  - Effect of electrostatic interactions on phase stability of cubic phases of
      membranes of monoolein/dioleoylphosphatidic acid mixtures.
AB  - To elucidate effects of electrostatic interactions resulting from surface charges
      on structures and phase stability of cubic phases of lipid membranes, membranes
      of 1-monoolein (MO) and dioleoylphosphatidic acid (DOPA) (DOPA/MO membrane)
      mixtures have been investigated by small-angle x-ray scattering method. As
      increasing DOPA concentration in the DOPA/MO membrane at 30 wt% lipid
      concentration, a phase transition from Q(224) to Q(229) phase occurred at 0.6
      mol% DOPA, and at and above 25 mol% DOPA, DOPA/MO membranes were in the L(alpha)
      phase. As NaCl concentration in the bulk phase increased, for 10% DOPA/90% MO
      membrane in excess water, a Q(229) to Q(224) phase transition occurred at 60 mM
      NaCl, and then a Q(224) to H(II) phase transition occurred at 1.2 M NaCl.
      Similarly, for 30% DOPA/70% MO membrane in excess water, at low NaCl
      concentrations it was in the L(alpha) phase, but at and above 0.50 M NaCl it was
      in the Q(224) phase, and then at 0.65 M NaCl a Q(224) to H(II) phase transition
      occurred. These results indicate that the electrostatic interactions in the
      membrane interface make the Q(229) phase more stable than the Q(224) phase, and
      that, at larger electrostatic interactions, the L(alpha) phase is more stable
      than the cubic phases (Q(224) and Q(229)). We have found that the addition of
      tetradecane to the MO membrane induced a Q(224)-to-H(II) phase transition and
      also that to the 30% DOPA/70% MO membrane induced an L(alpha)-to-H(II) phase
      transition. By using these membranes, the effect of the electrostatic
      interactions resulting from the membrane surface charge (DOPA) on the spontaneous
      curvature of the monolayer membrane has been investigated. The increase in DOPA
      concentration in the DOPA/MO membrane reduced the absolute value of spontaneous
      curvature of the membrane. In the 30% DOPA/70% MO membrane, the absolute value of
      spontaneous curvature of the membrane increased with an increase in NaCl
      concentration. On the basis of these new results, the phase stability of DOPA/MO
      membranes can be reasonably explained by the spontaneous curvature of the
      monolayer membrane and a curvature elastic energy of the membrane.

PMID- 11463641
TI  - ADP ribosylation factor 6 binding to phosphatidylinositol 4,5-bisphosphate
      containing vesicles creates defects in the bilayer structure: an electron spin
      resonance study.
AB  - The effects of binding of myristoylated ADP ribosylation factor 6 (myr-ARF6), an
      activator of phospholipase D (PLD), to a model membrane were investigated using
      an electron spin resonance (ESR) labeling technique. Initial studies were
      conducted in vesicles composed of 1-palmitoyl-2-oleoyl phosphatidylethanolamine,
      dipalmitoylphosphatidylcholine, phosphatidylinositol 4,5-biphosphate (PIP(2)),
      and cholesterol. Recombinant ARF6 binding significantly enhances defects in both
      the headgroup and acyl-chain regions of the membrane, which are revealed by the
      emergence of sharp components in the spectra from a headgroup label, 1,2
      dipalmitoylphosphatidyl-2,2,6,6-tetramethyl-1-piperidinyloxy-choline (DPPTC), and
      a chain label, 10PC, after myr-ARF6 binding. Binding of non-myristoylated ARF6
      (non-ARF6) shows markedly reduced effects. Interestingly, no change in spectra
      from DPPTC was observed upon myr-ARF6 binding when PIP(2) in the vesicles was
      replaced by other negatively charged lipids, including phosphatidylinositol,
      phosphatidylserine, and phosphatidylglycerol, even when normalized for charge.
      The production of the sharp peak appears to be a specific event, because another
      GTP binding protein, CDC42, which binds PIP(2) and activates PLD, fails to induce
      changes in vesicle structure. These results suggest a previously unappreciated
      role for ARF in mediating a protein/lipid interaction that produces defects in
      lipid bilayers. This function may serve as an initial event in destabilizing
      membrane structure for subsequent membrane fusion or biogenesis of vesicles.

PMID- 11463642
TI  - Phloretin-induced changes of lipophilic ion transport across the plasma membrane
      of mammalian cells.
AB  - The adsorption of the hydrophobic anion [W(CO)(5)CN](-) to human lymphoid Jurkat
      cells gave rise to an additional anti-field peak in the rotational spectra of
      single cells, indicating that the cell membrane displayed a strong dielectric
      dispersion in the kilohertz to megahertz frequency range. The surface
      concentration of the adsorbed anion and its translocation rate constant between
      the two membrane boundaries could be evaluated from the rotation spectra of cells
      by applying the previously proposed mobile charge model. Similar single-cell
      electrorotation experiments were performed to examine the effect of phloretin, a
      dipolar molecule known to influence the dipole potential of membranes, on the
      transport of [W(CO)(5)CN](-) across the plasma membrane of mammalian cells. The
      adsorption of [W(CO)(5)CN](-) was significantly reduced by phloretin, which is in
      reasonable agreement with the known phloretin-induced effects on artificial and
      biological membranes. The IC(50) for the effect of phloretin on the transport
      parameters of the lipophilic ion was approximately 10 microM. The results of this
      study are consistent with the assumption that the binding of phloretin reduces
      the intrinsic dipole potential of the plasma membrane. The experimental approach
      developed here allows the quantification of intrinsic dipole potential changes
      within the plasma membrane of living cells.

PMID- 11463643
TI  - Responding phospholipid membranes--interplay between hydration and permeability.
AB  - Osmotic forces are important in regulating a number of physiological membrane
      processes. The effect of osmotic pressure on lipid phase behavior is of utmost
      importance for the extracellular lipids in stratum corneum (the outer part of
      human skin), due to the large gradient in water chemical potential between the
      water-rich tissue on the inside, and the relative dry environment on the outside
      of the body. We present a theoretical model for molecular diffusional transport
      over an oriented stack of two-component lipid bilayers in the presence of a
      gradient in osmotic pressure. This gradient serves as the driving force for
      diffusional motion of water. It also causes a gradient in swelling and phase
      transformations, which profoundly affect the molecular environment and thus the
      local diffusion properties. This feedback mechanism generates a nonlinear
      transport behavior, which we illustrate by calculations of the flux of water and
      solute (nicotine) through the bilayer stack. The calculated water flux shows
      qualitative agreement with experimental findings for water flux through stratum
      corneum. We also present a physical basis for the occlusion effect. Phase
      behavior of binary phospholipid mixtures at varying osmotic pressures is modeled
      from the known interlamellar forces and the regular solution theory. A first
      order phase transformation from a gel to a liquid--crystalline phase can be
      induced by an increase in the osmotic pressure. In the bilayer stack, a
      transition can be induced along the gradient. The boundary conditions in water
      chemical potential can thus act as a switch for the membrane permeability.

PMID- 11463644
TI  - Assembly of a polytopic membrane protein structure from the solution structures
      of overlapping peptide fragments of bacteriorhodopsin.
AB  - Three-dimensional structures of only a handful of membrane proteins have been
      solved, in contrast to the thousands of structures of water-soluble proteins.
      Difficulties in crystallization have inhibited the determination of the three
      dimensional structure of membrane proteins by x-ray crystallography and have
      spotlighted the critical need for alternative approaches to membrane protein
      structure. A new approach to the three-dimensional structure of membrane proteins
      has been developed and tested on the integral membrane protein,
      bacteriorhodopsin, the crystal structure of which had previously been determined.
      An overlapping series of 13 peptides, spanning the entire sequence of
      bacteriorhodopsin, was synthesized, and the structures of these peptides were
      determined by NMR in dimethylsulfoxide solution. These structures were assembled
      into a three-dimensional construct by superimposing the overlapping sequences at
      the ends of each peptide. Onto this construct were written all the distance and
      angle constraints obtained from the individual solution structures along with a
      limited number of experimental inter-helical distance constraints, and the
      construct was subjected to simulated annealing. A three-dimensional structure,
      determined exclusively by the experimental constraints, emerged that was similar
      to the crystal structure of this protein. This result suggests an alternative
      approach to the acquisition of structural information for membrane proteins
      consisting of helical bundles.

PMID- 11463645
TI  - Computer simulation of the rough lipopolysaccharide membrane of Pseudomonas
      aeruginosa.
AB  - Lipopolysaccharides (LPSs) form the major constituent of the outer membrane of
      Gram-negative bacteria, and are believed to play a key role in processes that
      govern microbial metal binding, microbial adsorption to mineral surfaces, and
      microbe-mediated oxidation/reduction reactions at the bacterial exterior surface.
      A computational modeling capability is being developed for the study of
      geochemical reactions at the outer bacterial envelope of Gram-negative bacteria.
      A molecular model for the rough LPS of Pseudomonas aeruginosa has been designed
      based on experimentally determined structural information. An electrostatic model
      was developed based on Hartree-Fock SCF calculations of the complete LPS molecule
      to obtain partial atomic charges. The exterior of the bacterial membrane was
      assembled by replication of a single LPS molecule and a single phospholipid
      molecule. Molecular dynamics simulations of the rough LPS membrane of P.
      aeruginosa were carried out and trajectories were analyzed for the energetic and
      structural factors that determine the role of LPS in processes at the cell
      surface.

PMID- 11463646
TI  - Rational design of lipid molecular structure: a case study involving the C19:1c10
      monoacylglycerol.
AB  - The phase properties of lipids have far-reaching consequences in membrane
      biology. Their influence ranges from domain formation in intact biomembranes to
      membrane protein reconstitution and crystallization. To exploit phase behavior in
      the spirit of rational design, it is imperative that the rules relating lipid
      molecular structure and liquid crystal or mesophase behavior be established.
      Phase behavior is quantitatively and concisely represented in the form of
      temperature-composition phase diagrams. A somewhat limited number of phase
      diagrams exists for the monoacylglycerols. The objective of the current study was
      to determine the quality of phase behavior prediction for a specific
      monoacylglycerol based on an analysis of the existing phase diagrams for related
      chain homologs. To this end, a phase diagram for the monononadecenoin
      (19:1c10)/water system was predicted in the temperature range from -15 degrees C
      to 120 degrees C and from 0% to 80% (w/w) water. The prediction was tested by
      constructing the corresponding phase diagram using low- and wide-angle x-ray
      diffraction, differential scanning calorimetry, and polarized light microscopy.
      The results show that the predicted and experimental phase diagrams agree
      remarkably well. They also highlight the need for additional phase studies of the
      type described to enlarge the data bank of phase diagrams and to strengthen the
      foundations of the rational design approach.

PMID- 11463647
TI  - Atomic force microscopy studies of ganglioside GM1 domains in phosphatidylcholine
      and phosphatidylcholine/cholesterol bilayers.
AB  - The distribution of ganglioside in supported lipid bilayers has been studied by
      atomic force microscopy. Hybrid dipalmitoylphosphatidylcholine
      (DPPC)/dipalmitoylphosphatidylethanolamine (DPPE) and (2:1 DPPC/cholesterol)/DPPE
      bilayers were prepared using the Langmuir Blodgett technique. Egg PC and DPPC
      bilayers were prepared by vesicle fusion. Addition of ganglioside GM1 to each of
      the lipid bilayers resulted in the formation of heterogeneous surfaces that had
      numerous small raised domains (30--200 nm in diameter). Incubation of these
      bilayers with cholera toxin B subunit resulted in the detection of small protein
      aggregates, indicating specific binding of the protein to the GM1-rich
      microdomains. Similar results were obtained for DPPC, DPPC/cholesterol, and egg
      PC, demonstrating that the overall bilayer morphology was not dependent on the
      method of bilayer preparation or the fluidity of the lipid mixture. However,
      bilayers produced by vesicle fusion provided evidence for asymmetrically
      distributed GM1 domains that probably reflect the presence of ganglioside in both
      inner and outer monolayers of the initial vesicle. The results are discussed in
      relation to recent inconsistencies in the estimation of sizes of lipid rafts in
      model and natural membranes. It is hypothesized that small ganglioside-rich
      microdomains may exist within larger ordered domains in both natural and model
      membranes.

PMID- 11463648
TI  - Multiple structures of thick filaments in resting cardiac muscle and their
      influence on cross-bridge interactions.
AB  - Based on two criteria, the tightness of packing of myosin rods within the
      backbone of the filament and the degree of order of the myosin heads, thick
      filaments isolated from a control group of rat hearts had three different
      structures. Two of the structures of thick filaments had ordered myosin heads and
      were distinguishable from each other by the difference in tightness of packing of
      the myosin rods. Depending on the packing, their structure has been called loose
      or tight. The third structure had narrow shafts and disordered myosin heads
      extending at different angles from the backbone. This structure has been called
      disordered. After phosphorylation of myosin-binding protein C (MyBP-C) with
      protein kinase A (PKA), almost all thick filaments exhibited the loose structure.
      Transitions from one structure to another in quiescent muscles were produced by
      changing the concentration of extracellular Ca. The probability of interaction
      between isolated thick and thin filaments in control, PKA-treated preparations,
      and preparations exposed to different Ca concentrations was estimated by electron
      microscopy. Interactions were more frequent with phosphorylated thick filaments
      having the loose structure than with either the tight or disordered structure. In
      view of the presence of MgATP and the absence of Ca, the interaction between the
      myosin heads and the thin filaments was most likely the weak attachment that
      precedes the force-generating steps in the cross-bridge cycle. These results
      suggest that phosphorylation of MyBP-C in cardiac thick filaments increases the
      probability of cross-bridges forming weak attachments to thin filaments in the
      absence of activation. This mechanism may modulate the number of cross-bridges
      generating force during activation.

PMID- 11463649
TI  - Changes in cardiac contractility related to calcium-mediated changes in
      phosphorylation of myosin-binding protein C.
AB  - Ca ions can influence the contraction of cardiac muscle by activating kinases
      that specifically phosphorylate the myofibrillar proteins myosin-binding protein
      C (MyBP-C) and the regulatory light chain of myosin (RLC). To investigate the
      possible role of Ca-regulated phosphorylation of MyBP-C on contraction, isolated
      quiescent and rhythmically contracting cardiac trabeculae were exposed to
      different concentrations of extracellular Ca and then chemically skinned to clamp
      the contractile system. Maximum Ca-activated force (F(max)) was measured in
      quiescent cells soaking in 1) 2.5 mM Ca for 120 min, 2) 1.25 mM for 120 min, or
      3) 1.25 mM for 120 min followed by 10 min in 7.5 mM, and 4) cells rhythmically
      contracting in 2.5 mM for 20 min. F(max) was, respectively, 21.5, 10.5, 24.7, and
      32.6 mN/mm(2). Changes in F(max) were closely associated with changes in the
      degree of phosphorylation of MyBP-C and occurred at intracellular concentrations
      of Ca below levels associated with phosphorylation of RLC. Monophosphorylation of
      MyBP-C by a Ca-regulated kinase is necessary before beta-adrenergic stimulation
      can produce additional phosphorylation. These results suggest that Ca-dependent
      phosphorylation of MyBP-C modulates contractility by changing thick filament
      structure.

PMID- 11463650
TI  - Quantal sarcomere-length changes in relaxed single myofibrils.
AB  - We carried out experiments on single isolated myofibrils in which thin filaments
      had been functionally removed, leaving the connecting (titin) filaments as the
      sole agent taking up the length change. With technical advances that gave sub
      nanometer detectability we examined the time course of single sarcomere-length
      change when the myofibril was ramp-released or ramp-stretched by a motor. The
      sarcomere-length change was stepwise. Step sizes followed a consistent pattern:
      the smallest was approximately 2.3 nm, and others were integer multiples of that
      value. The approximately 2.3-nm step quantum is the smallest consistent
      biomechanical event ever demonstrated. Although the length change must involve
      the connecting filament, the size of the quantum is an order of magnitude smaller
      than anticipated from folding of Ig- or fibronectin-like domains, implying either
      that folding occurs in sub-domain units or that other mechanisms are involved.

PMID- 11463651
TI  - Effect of ionic strength on the conformation of myosin subfragment 1-nucleotide
      complexes.
AB  - The effect of ionic strength on the conformation and stability of S1 and S1
      nucleotide-phosphate analog complexes in solution was studied. It was found that
      increasing concentration of KCl enhances the reactivity of Cys(707) (SH1 thiol)
      and Lys(84) (reactive lysyl residue) and the nucleotide-induced tryptophan
      fluorescence increment. In contrast, high KCl concentration lowers the structural
      differences between the intermediate states of ATP hydrolysis in the vicinity of
      Cys(707), Trp(510) and the active site, possibly by increasing the flexibility of
      the molecule. High concentrations of neutral salts inhibit both the formation and
      the dissociation of the M**.ADP.Pi analog S1.ADP.Vi complex. High ionic strength
      profoundly affects the structure of the stable S1.ADP.BeF(x) complex, by
      destabilizing the M*.ATP intermediate, which is the predominant form of the
      complex at low ionic strength, and shifting the equilibrium to favor the
      M**.ADP.Pi state. The M*.ATP intermediate is destabilized by perturbation of
      ionic interactions possibly by disruption of salt bridges. Two salt-bridge pairs,
      Glu(501)-Lys(505) in the Switch II helix and Glu(776)-Lys(84) connecting the
      catalytic domain to the lever arm, seem most appropriate to consider for
      participating in the ionic strength-induced transition of the open M*.ATP to the
      closed M**.ADP.Pi state of S1.

PMID- 11463652
TI  - Probing the structure and dynamics of a DNA hairpin by ultrafast quenching and
      fluorescence depolarization.
AB  - DNA hairpins have been investigated in which individual adenines were replaced by
      their fluorescent analog 2-aminopurine (2AP). The temperature dependence of the
      time evolution of polarized emission spectra was monitored with picosecond time
      resolution. Four isotropic decay components for each oligonucleotide indicated
      the coexistence of at least four conformations. The fluorescence for three of
      these was significantly quenched, which is explained by hole transfer from 2AP to
      guanine(s). An approximately 8-ps component is ascribed to direct hole transfer,
      the approximately 50-ps and approximately 500-ps components are ascribed to
      structural reorganization, preceding hole transfer. At room temperature, a
      fraction remains unquenched on a 10-ns timescale, in contrast to higher
      temperatures, where the flexibility increases. Besides quenching due to base
      stacking, a second quenching process was needed to describe the data. Evidence
      for both intrastrand and interstrand hole transfer was found. The extracted
      probability for stacking between neighboring bases in double-stranded regions was
      estimated to be approximately 75% at room temperature and approximately 25% at 80
      degrees C, demonstrating structural disorder of the DNA. Fluorescence
      depolarization revealed both local dynamics of the DNA and overall dynamics of
      the entire oligonucleotide. Upon raising the temperature, the C-N terminus of the
      hairpin appears to melt first; the rest of the hairpin denatures above the
      average melting temperature.

PMID- 11463653
TI  - Aggregation of nucleosomes by divalent cations.
AB  - Conditions of precipitation of nucleosome core particles (NCP) by divalent
      cations (Ca(2+) and Mg(2+)) have been explored over a large range of nucleosome
      and cation concentrations. Precipitation of NCP occurs for a threshold of
      divalent cation concentration, and redissolution is observed for further addition
      of salt. The phase diagram looks similar to those obtained with DNA and synthetic
      polyelectrolytes in the presence of multivalent cations, which supports the idea
      that NCP/NCP interactions are driven by cation condensation. In the phase
      separation domain the effective charge of the aggregates was determined by
      measurements of their electrophoretic mobility. Aggregates formed in the presence
      of divalent cations (Mg(2+)) remain negatively charged over the whole
      concentration range. They turn positively charged when aggregation is induced by
      trivalent (spermidine) or tetravalent (spermine) cations. The higher the valency
      of the counterions, the more significant is the reversal of the effective charge
      of the aggregates. The sign of the effective charge has no influence on the
      aspect of the phase diagram. We discuss the possible reasons for this charge
      reversal in the light of actual theoretical approaches.

PMID- 11463654
TI  - Stretching single-stranded DNA: interplay of electrostatic, base-pairing, and
      base-pair stacking interactions.
AB  - Recent single-macromolecule observations revealed that the force/extension
      characteristics of single-stranded DNA (ssDNA) are closely related to solution
      ionic concentration and DNA sequence composition. To understand this, we studied
      the elastic property of ssDNA through the Monte Carlo implementation of a
      modified freely jointed chain (FJC), with electrostatic, base-pairing, and base
      pair stacking interactions all incorporated. The simulated force-extension
      profiles for both random and designed sequences have attained quantitative
      agreements with the experimental data. In low-salt solution, electrostatic
      interaction dominates, and at low forces, the molecule can be more easily aligned
      than an unmodified FJC. In high-salt solution, secondary hairpin structure
      appears in ssDNA by the formation of base pairs between complementary bases, and
      external stretching causes a hairpin-coil structural transition, which is
      continuous for ssDNA made of random sequences. In designed sequences such as
      poly(dA-dT) and poly(dG-dC), the stacking potential between base pairs encourages
      the aggregation of base pairs into bulk hairpins and makes the hairpin-coil
      transition a discontinuous (first-order) process. The sensitivity of elongation
      to the base-pairing rule is also investigated. The comparison of modeling
      calculations and the experimental data suggests that the base pairing of single
      stranded polynucleotide molecules tends to form a nested and independent planar
      hairpin structure rather than a random intersecting pattern.

PMID- 11463655
TI  - Spectral inhomogeneity of photosystem I and its influence on excitation
      equilibration and trapping in the cyanobacterium Synechocystis sp. PCC6803 at 77
      K.
AB  - Ultrafast transient absorption spectroscopy was used to probe excitation energy
      transfer and trapping at 77 K in the photosystem I (PSI) core antenna from the
      cyanobacterium Synechocystis sp. PCC 6803. Excitation of the bulk antenna at 670
      and 680 nm induces a subpicosecond energy transfer process that populates the Chl
      a spectral form at 685--687 nm within few transfer steps (300--400 fs). On a
      picosecond time scale equilibration with the longest-wavelength absorbing
      pigments occurs within 4-6 ps, slightly slower than at room temperature. At low
      temperatures in the absence of uphill energy transfer the energy equilibration
      processes involve low-energy shifted chlorophyll spectral forms of the bulk
      antenna participating in a 30--50-ps process of photochemical trapping of the
      excitation by P(700). These spectral forms might originate from clustered
      pigments in the core antenna and coupled chlorophylls of the reaction center.
      Part of the excitation is trapped on a pool of the longest-wavelength absorbing
      pigments serving as deep traps at 77 K. Transient hole burning of the ground
      state absorption of the PSI with excitation at 710 and 720 nm indicates
      heterogeneity of the red pigment absorption band with two broad homogeneous
      transitions at 708 nm and 714 nm (full-width at half-maximum (fwhm) approximately
      200--300 cm(-1)). The origin of these two bands is attributed to the presence of
      two chlorophyll dimers, while the appearance of the early time bleaching bands at
      683 nm and 678 nm under excitation into the red side of the absorption spectrum
      (>690 nm) can be explained by borrowing of the dipole strength by the ground
      state absorption of the chlorophyll a monomers from the excited-state absorption
      of the dimeric red pigments.

PMID- 11463656
TI  - Specific binding sites for cations in bacteriorhodopsin.
AB  - The Asp-85 residue, located in the vicinity of the retinal chromophore, plays a
      key role in the function of bacteriorhodopsin (bR) as a light-driven proton pump.
      In the unphotolyzed pigment the protonation of Asp-85 is responsible for the
      transition from the purple form (lambda(max) = 570 nm) to the blue form
      (lambda(max) = 605 nm) of bR. This transition can also be induced by deionization
      (cation removal). It was previously proposed that the cations bind to the bR
      surface and raise the surface pH, or bind to a specific site in the protein,
      probably in the retinal vicinity. We have reexamined these possibilities by
      evaluating the interaction between Mn(2+) and a nitroxyl radical probe covalently
      bound to several mutants in which protein residues were substituted by cystein.
      We have found that Mn(2+), which binds to the highest-affinity binding site,
      significantly affects the EPR spectrum of a spin label attached to residue 74C.
      Therefore, it is concluded that the highest-affinity binding site is located in
      the extracellular side of the protein and its distance from the spin label at 74C
      is estimated to be approximately 9.8 +/- 0.7 A. At least part of the three to
      four low-affinity cation binding sites are located in the cytoplasmic side,
      because Mn(2+) bound to these binding sites affects spin labels attached to
      residues 103C and 163C located in the cytoplasmic side of the protein. The
      results indicate specific binding sites for the color-controlling cations, and
      suggest that the binding sites involve negatively charged lipids located on the
      exterior of the bR trimer structure.

PMID- 11463657
TI  - Fluorescence emission spectral shift measurements of membrane potential in single
      cells.
AB  - Previous measurements of transmembrane potential using the electrochromic probe
      di-8-ANEPPS have used the excitation spectral shift response by alternating
      excitation between two wavelengths centered at voltage-sensitive portions of the
      excitation spectrum and recording at a single wavelength near the peak of the
      emission spectrum. Recently, the emission spectral shift associated with the
      change in transmembrane potential has been used for continuous membrane potential
      monitoring. To characterize this form of the electrochromic response from di-8
      ANEPPS, we have obtained fluorescence signals from single cells in response to
      step changes in transmembrane potentials set with a patch electrode, using single
      wavelength excitation near the peak of the dye absorption spectrum. Fluorescence
      changes at two wavelengths near voltage-sensitive portions of the emission
      spectrum and shifts in the complete emission spectrum were determined for
      emission from plasma membrane and internal membrane. We found that the
      fluorescence ratio from either dual-wavelength recordings, or from opposite sides
      of the emission spectrum, varied linearly with the amplitude of the transmembrane
      potential step between -80 and +60 mV. Voltage dependence of difference spectra
      exhibit a crossover point near the peak of the emission spectra with
      approximately equal gain and loss of fluorescence intensity on each side of the
      spectrum and equal response amplitude for depolarization and hyperpolarization.
      These results are consistent with an electrochromic mechanism of action and
      demonstrate how the emission spectral shift response can be used to measure the
      transmembrane potential in single cells.

PMID- 11463658
TI  - Crystal structure of R-phycocyanin and possible energy transfer pathways in the
      phycobilisome.
AB  - The crystal structure of R-phycocyanin from Polysiphonia urceolata (R-PC-PU) at
      2.4 A is reported. The R-PC-PU crystal belongs to space group P4(3)2(1)2 with
      cell parameters a = 135.1 A, c = 210.0 A, and alpha = beta = gamma = 90 degrees.
      The structure was determined by molecular replacement. The crystallographic R
      factor of the refined model is 0.189 (R(free) = 0.239). Comparison of the
      microenvironment of chromophore beta 155 in R-PC-PU and in C-PC from Fremyolla
      diphosiphon (C-PC-FD) reveals that their spectral differences may be caused by
      their different alpha 28 residues. In the R-PC-PU crystal structure, two (alpha
      beta)(3) trimers assemble face to face to form a hexamer, and two such hexamers
      assemble in two novel side-to-side arrangements. Possible models for the energy
      transfer from phycoerythrin to phycocyanin and from phycocyanin to
      allophycocyanin are proposed based on several phycobiliprotein crystal
      structures.

PMID- 11463659
TI  - Fluorescence study of conformational properties of melanotropins labeled with
      aminobenzoic acid.
AB  - The native hormone alpha-melanocyte-stimulating hormone (alpha-MSH) and its more
      potent analog [Nle(4),D-Phe(7)]alpha-MSH (NDP-alpha MSH), labeled at the amino
      terminal with the fluorescent aminobenzoic acid (Abz) isomers, were examined by
      fluorescence methods. We observed energy transfer between the tryptophan(9)
      residue acting as donor and Abz as acceptor, the transfer being more pronounced
      to the ortho-form of the acceptor. Within the hypothesis that different peptide
      conformations coexist in equilibrium during the fluorescence decay, we supposed
      that the intensity decay was modulated by an acceptor-donor distance distribution
      function f(r). From the time-resolved fluorescence experimental data, we
      recovered the distance distribution between Abz and Trp(9), using the CONTIN
      program, within the framework of the Forster resonance energy transfer model. The
      methodology proved to be useful to provide quantitative information about
      conformational dynamics of melanotropins and its dependency on the solvent. In
      aqueous medium, alpha-MSH has a broad Abz-Trp(9) distance distribution,
      reflecting the structural flexibility of the peptide. Three different distance
      populations could be identified in the labeled analog NDP-alpha MSH in water,
      indicating distinct conformational states for the synthetic peptide, compared
      with the native hormone. Measurements in trifluoroethanol resulted in the
      recovery of two Abz-Trp(9) distance populations, both for the native and the
      analog hormones, reflecting the decrease, induced by the solvent, of the
      conformational states available to the peptides.

PMID- 11463660
TI  - Mean square fluctuations of hydrogen atoms and water-biopolymer interactions in
      hydrated saccharides.
AB  - We have used the elastic neutron scattering technique to investigate the dynamics
      of the two main saccharidic components of starch: amylose and amylopectin. The
      measurements were carried out in the temperature range of 20 to 320 K and at
      different hydration levels from the dry state up to 0.47 g saccharide/g D(2)O. In
      the dry samples, the atomic dynamics is harmonic up to approximately 300 K. In
      the hydrated samples a "glass-like" transition leading to an anharmonic dynamics
      is observed. The onset of the anharmonicity occurs at temperatures that increase
      from approximately 180 K to 260 K upon decreasing hydration from 0.5 to 0.1 g
      saccharide/g D(2)O. This behavior is qualitatively similar to that observed in
      hydrated globular proteins, but quantitative differences are present. Assuming a
      simple asymmetric double-well potential model, the temperature and hydration
      dependence of the transition have been described in terms of few physical
      parameters.

PMID- 11463661
TI  - Substrate binding to DNA photolyase studied by electron paramagnetic resonance
      spectroscopy.
AB  - Structural changes in Escherichia coli DNA photolyase induced by binding of a
      (cis,syn)-cyclobutane pyrimidine dimer (CPD) are studied by continuous-wave
      electron paramagnetic resonance and electron-nuclear double resonance
      spectroscopies, using the flavin adenine dinucleotide (FAD) cofactor in its
      neutral radical form as a naturally occurring electron spin probe. The electron
      paramagnetic resonance/electron-nuclear double resonance spectral changes are
      consistent with a large distance (> or =0.6 nm) between the CPD lesion and the
      7,8-dimethyl isoalloxazine ring of FAD, as was predicted by recent model
      calculations on photolyase enzyme-substrate complexes. Small shifts of the
      isotropic proton hyperfine coupling constants within the FAD's isoalloxazine
      moiety can be understood in terms of the cofactor binding site becoming more
      nonpolar because of the displacement of water molecules upon CPD docking to the
      enzyme. Molecular orbital calculations of hyperfine couplings using density
      functional theory, in conjunction with an isodensity polarized continuum model,
      are presented to rationalize these shifts in terms of the changed polarity of the
      medium surrounding the FAD cofactor.

PMID- 11463662
TI  - The third generation pill controversy ("continued").

PMID- 11463663
TI  - Poverty reduction strategy papers.

PMID- 11463664
TI  - Vocational rehabilitation.

PMID- 11463665
TI  - Drugs for Alzheimer's disease.

PMID- 11463667
TI  - UK approves preimplantation genetic screening technique.

PMID- 11463668
TI  - Mortality for paediatric cardiac surgery at Bristol was twice that at other
      centres.

PMID- 11463671
TI  - US abortion clinics afraid of new violence.

PMID- 11463670
TI  - Tobacco company claims that smokers help the economy.

PMID- 11463672
TI  - Scientists fertilise mouse eggs without sperm.

PMID- 11463674
TI  - GMC steps up hearings to deal with rise in cases.

PMID- 11463675
TI  - Bill will give Americans right to buy cheaper drugs.

PMID- 11463676
TI  - Levels of neurosis remained static in the 1990s.

PMID- 11463677
TI  - Government decision to hand over GP negotiations branded "bizarre".

PMID- 11463678
TI  - Third generation oral contraceptives and risk of venous thrombosis: meta
      analysis.
AB  - OBJECTIVE: To evaluate quantitatively articles that compared effects of second
      and third generation oral contraceptives on risk of venous thrombosis. DESIGN:
      Meta-analysis. STUDIES: Cohort and case-control studies assessing risk of venous
      thromboembolism among women using oral contraceptives before October 1995. MAIN
      OUTCOME MEASURES: Pooled adjusted odds ratios calculated by a general variance
      based random effects method. When possible, two by two tables were extracted and
      combined by the Mantel-Haenszel method. RESULTS: The overall adjusted odds ratio
      for third versus second generation oral contraceptives was 1.7 (95% confidence
      interval 1.4 to 2.0; seven studies). Similar risks were found when oral
      contraceptives containing desogestrel or gestodene were compared with those
      containing levonorgestrel. Among first time users, the odds ratio for third
      versus second generation preparations was 3.1 (2.0 to 4.6; four studies). The
      odds ratio was 2.5 (1.6 to 4.1; five studies) for short term users compared with
      2.0 (1.4 to 2.7; five studies) for longer term users. The odds ratio was 1.3 (1.0
      to 1.7) in studies funded by the pharmaceutical industry and 2.3 (1.7 to 3.2) in
      other studies. Differences in age and certainty of diagnosis of venous thrombosis
      did not affect the results. CONCLUSIONS: This meta-analysis supports the view
      that third generation oral contraceptives are associated with an increased risk
      of venous thrombosis compared with second generation oral contraceptives. The
      increase cannot be explained by several potential biases.

PMID- 11463679
TI  - Randomised controlled trial of brief psychological intervention after deliberate
      self poisoning.
AB  - OBJECTIVES: To determine the effects of a brief psychological intervention (brief
      psychodynamic interpersonal therapy) for patients after deliberate self poisoning
      compared with usual treatment. To compare the impact of the active intervention
      and usual treatment on patients' satisfaction with care. DESIGN: Randomised
      controlled trial. PARTICIPANTS: 119 adults who had deliberately poisoned
      themselves and presented to the emergency department of a teaching hospital.
      SETTING: Community based study. INTERVENTION: Four sessions of therapy delivered
      in the patient's home. Control patients received "treatment as usual," which in
      most cases consisted of referral back to their general practitioner. OUTCOME
      MEASURES: Severity of suicidal ideation six months after treatment as assessed by
      the Beck scale for suicidal ideation. Secondary outcome measures at six month
      follow up included depressive symptoms as measured by the Beck depression
      inventory, patient satisfaction with treatment, and self reported subsequent
      attempts at self harm. RESULTS: Participants randomised to the intervention had a
      significantly greater reduction in suicidal ideation at six month follow up
      compared with those in the control group (reduction in the mean (SD) Beck scale
      8.0 v 1.5). They were more satisfied with their treatment and were less likely to
      report repeated attempts to harm themselves at follow up (proportion repeating 9%
      v 28% in control group; difference 19%, 95% confidence interval 9% to 30 %,
      P=0.009). CONCLUSION: Brief psychodynamic interpersonal therapy may be a valuable
      treatment after people have deliberately tried to poison themselves.

PMID- 11463681
TI  - Condom gap in Africa: evidence from donor agencies and key informants.

PMID- 11463682
TI  - Risk of breast cancer in women who attend the NHS breast screening programme:
      cohort study.

PMID- 11463683
TI  - Survival of trauma patients who have prehospital tracheal intubation without
      anaesthesia or muscle relaxants: observational study.

PMID- 11463686
TI  - Managing demand: transfer of management of self limiting conditions from general
      practice to community pharmacies.

PMID- 11463685
TI  - Relation between insufficient response to antihypertensive treatment and poor
      compliance with treatment: a prospective case-control study.
AB  - OBJECTIVES: To prospectively compare compliance with treatment in patients with
      hypertension responsive to treatment versus patients with treatment resistant
      hypertension. DESIGN: Prospective case-control study. SETTING: Outpatient
      department in a large city hospital in Switzerland, providing primary, secondary,
      and tertiary care. PARTICIPANTS: 110 consecutive medical outpatients with
      hypertension and taking stable treatment with at least two antihypertensive drugs
      for at least four weeks. MAIN OUTCOME MEASURES: Treatment compliance assessed
      with MEMS devices; blood pressure determined by 12 hour daytime ambulatory
      monitoring (pressure <135/85 mm Hg in patients aged </=60 years and <155/90 mm Hg
      in patients aged >60 indicated hypertension responsive to treatment). RESULTS:
      Complete data were available for 103 patients, of whom 86 took >/=80% of their
      prescribed doses ("compliant") and 17 took <80% ("non-compliant"). Of the 49
      patients with treatment resistant hypertension, 40 (82%) were compliant, while 46
      (85%) of the 54 patients responsive to treatment were compliant. CONCLUSION: Non
      compliance with treatment was not more prevalent in patients with treatment
      resistant hypertension than in treatment responsive patients.

PMID- 11463687
TI  - Evidence based case report: Assessing developmental delay.

PMID- 11463688
TI  - Lesson of the week: Danger of stereotyping in suspected osteomalacia.

PMID- 11463689
TI  - A global health fund: a leap of faith?

PMID- 11463690
TI  - When should clinical guidelines be updated?

PMID- 11463691
TI  - Systematic reviews in health care: Systematic reviews of evaluations of
      diagnostic and screening tests.

PMID- 11463692
TI  - Measles, mumps, and rubella (MMR) vaccine and autism. Ecological studies cannot
      answer main question.

PMID- 11463693
TI  - Asthma and early childhood infectious disease. Infection is trigger rather than
      cause.

PMID- 11463694
TI  - Using clinical evidence. Randomised controlled trials are not the only evidence.

PMID- 11463695
TI  - Code of conduct is needed for publishing raw data.

PMID- 11463697
TI  - Lay members can contribute much in primary care groups.

PMID- 11463698
TI  - Spirit of collaboration needs fostering.

PMID- 11463699
TI  - Questionnaires for depression and anxiety. Systematic review is incomplete.

PMID- 11463711
TI  - Circulation research impact factor sets new record.

PMID- 11463700
TI  - Exposure of healthcare workers to bloodborne viruses. Only the tip of the iceberg
      has been measured.

PMID- 11463712
TI  - Atherosclerosis modified.

PMID- 11463713
TI  - Heme oxygenase-1 protects the heart.

PMID- 11463714
TI  - The cytoplasm: no longer a well-mixed bag.

PMID- 11463715
TI  - Abnormal balance in the angiopoietin-tie2 system in human brain arteriovenous
      malformations.
AB  - Brain arteriovenous malformations (BAVMs) are congenital vascular lesions that
      often present as cerebral hemorrhage in young adults. The variable nature of the
      clinical course, especially with respect to spontaneous hemorrhage, recurrence,
      growth, and regression, suggests that BAVMs are lesions with active angiogenesis
      and vascular remodeling. We examined mRNA and protein expression of angiopoietin
      1 (Ang1) and Ang2 by semiquantitative reverse transcriptase-polymerase chain
      reaction, in situ hybridization, and Western blot in BAVMs and control brains
      obtained from temporal lobectomy for medically intractable seizures. Although
      Ang1 mRNA levels were similar in BAVMs and controls, Ang1 protein levels were 30%
      lower in BAVMs than in controls. Ang2 mRNA levels were 40% higher and Ang2
      protein levels were 8-fold higher in BAVMs than in controls. In situ
      hybridization showed that the Ang2 mRNA was localized to the perivascular area in
      BAVMs. This abnormal balance in the Ang-Tie2 system may, in part, explain the
      aberrant vascular phenotype in BAVMs.

PMID- 11463716
TI  - Redox signaling of the arteriolar myogenic response.
AB  - Arteriolar vascular smooth muscle cells (VSMCs) are mechanosensitive,
      constricting to elevations in transmural pressure (P(TM)). The goal of the
      present study was to determine using mouse isolated tail arterioles and arteries
      whether oxidant signaling regulates this myogenic response. In response to P(TM)
      elevation, VSMCs of arterioles but not arteries generated constriction and
      increased reactive oxygen species (ROS) activity (using the H(2)O(2)-sensitive
      probe dichlorodihydrofluorescein). Arterioles had increased expression of NADPH
      oxidase components compared with arteries. Inhibition of NADPH oxidase, using
      mice with targeted impairment of enzyme components (p47(phox) or rac1) or
      diphenyleneiodonium, prevented the pressure-induced generation of ROS. When ROS
      activity was inhibited, either by inhibiting NADPH oxidase or with N
      acetylcysteine, the myogenic constriction was abolished. The myogenic
      constriction was also inhibited by catalase, which inactivates H(2)O(2), but was
      unaffected by a cell-permeant mimic of superoxide dismutase (MnTMPyP). alpha(1)
      Adrenergic constriction was not associated with altered ROS activity and was not
      affected by inhibition of NADPH oxidase or ROS. Exogenous H(2)O(2) constricted
      VSMCs of arterioles but not arteries. Thus, NADPH oxidase and ROS, in particular
      H(2)O(2), contribute to the myogenic response of arteriolar VSMCs.

PMID- 11463717
TI  - Regulation of vascular bed-specific prothrombotic potential.
AB  - Hemostasis is the result of interdependent and complex systemic and local
      endothelial pathways that govern vascular integrity and rheology. A striking
      feature of hypercoagulable conditions is the focal nature of the resultant
      thrombotic pathology. Such disorders in hemostasis may be associated with
      distinct vascular beds, thus implying that the relative combined contribution of
      individual regulatory pathways may be specific and/or unique to a particular
      locale in the vasculature. Systemic factors and platelets mediate the formation
      of fibrin deposition; however, it is the diverse interrelationships in the
      interaction of these systemic elements with the local endothelial components that
      dictate vascular bed-specific hemostatic regulation. Indeed, the local activation
      of coagulation cascades, rather than increases in systemic thrombotic potential,
      is what leads to fibrin formation in different vascular beds. Hence, the
      propensity for congenital or acquired disorders to result in local thrombotic
      pathology is based on the relative contribution of the various hemostatic
      regulatory pathways in individual vascular beds. The present review highlights
      the role of local endothelial regulation in the interaction between local and
      systemic elements that contribute to vascular bed-specific prothrombotic
      potential.

PMID- 11463718
TI  - Genetic locus in mice that blocks development of atherosclerosis despite extreme
      hyperlipidemia.
AB  - The genes contributing to the common forms of atherosclerosis are largely
      unknown. One approach to dissecting complex traits such as atherosclerosis is to
      use animal models, such as the mouse, to map and characterize the genetic loci
      involved. We now report the identification of a locus for aortic lesion formation
      on mouse chromosome 6 that exhibits a highly significant lod score of 6.7 in a
      genetic cross between the susceptible strain, C57BL/6J, and the resistant strain,
      CAST/Ei. The locus was confirmed by constructing a congenic strain in which the
      chromosome 6 segment from CAST/Ei was transferred to a C57BL/6J background in a
      series of backcrosses. The congenic strain was almost completely resistant to
      diet-induced atherosclerosis. The chromosome 6 segment was also transferred onto
      the background of an LDL receptor-null mutation and resulted again in almost
      complete resistance to aortic lesion formation. This locus also influenced
      insulin levels but did not affect plasma lipoprotein levels, blood pressure, or
      body fat. The chromosome 6 gene, which we call Artles (for arterial lesions), did
      not affect endothelial cell responses to oxidized LDL, but lesion formation was
      partially reduced through bone marrow transplantation. The locus contains the
      candidate gene peroxisome proliferator-activated receptor-gamma, and the congenic
      mice exhibited significantly reduced expression of peroxisome proliferator
      activated receptor-gamma.

PMID- 11463719
TI  - Prx1 controls vascular smooth muscle cell proliferation and tenascin-C expression
      and is upregulated with Prx2 in pulmonary vascular disease.
AB  - Prx1 and Prx2 are homeobox transcription factors expressed during vasculogenesis.
      To begin to elucidate how Prx1 and Prx2 are regulated and function in the adult
      vasculature, in situ hybridization studies were performed. Prx1 and Prx2 mRNAs
      were not detected in normal adult rat pulmonary arteries; however, both genes
      were induced with vascular disease, colocalizing to sites of tenascin-C (TN-C)
      expression. Because catabolism of the extracellular matrix (ECM) is a critical
      step in the development of vascular disease, we investigated whether changes in
      vascular smooth muscle cell (SMC)-ECM interactions regulate Prx1 and Prx2. A10
      SMCs cultured on native type I collagen showed low levels of Prx1 and Prx2 mRNA
      expression, whereas cells cultured on denatured collagen showed higher levels of
      expression of both genes. At a functional level, transfection of SMCs with a Prx1
      expression plasmid significantly increased their growth. Because TN-C also
      promotes SMC growth and its expression is also upregulated by denatured collagen,
      we tested and thereafter showed that Prx1 expression significantly enhances TN-C
      gene promoter activity 20-fold. Similar experiments conducted with truncated Prx1
      proteins showed that the N-terminal portion and the homeodomain of Prx1 were
      necessary to induce the bulk of TN-C promoter activity. These findings support
      the hypothesis that Prx genes are regulated by changes in SMC adhesion and play
      key morphoregulatory roles during the development and progression of pulmonary
      vascular disease in adults.

PMID- 11463720
TI  - UT-A urea transporter protein in heart: increased abundance during uremia,
      hypertension, and heart failure.
AB  - Urea transporters have been cloned from kidney medulla (UT-A) and erythrocytes
      (UT-B). We determined whether UT-A proteins could be detected in heart and
      whether their abundance was altered by uremia or hypertension or in human heart
      failure. In normal rat heart, bands were detected at 56, 51, and 39 kDa. In
      uremic rats, the abundance of the 56-kDa protein increased 1.9-fold compared with
      pair-fed, sham-operated rats, whereas the 51- and 39-kDa proteins were unchanged.
      We also detected UT-A2 mRNA in hearts from control and uremic rats. Because
      uremia is accompanied by hypertension, the effects of hypertension per se were
      studied in uninephrectomized deoxycorticosterone acetate salt-treated rats, where
      the abundance of the 56-kDa protein increased 2-fold versus controls, and in
      angiotensin II-infused rats, where the abundance of the 56 kDa protein increased
      1.8-fold versus controls. The 51- and 39-kDa proteins were unchanged in both
      hypertensive models. In human left ventricle myocardium, UT-A proteins were
      detected at 97, 56, and 51 kDa. In failing left ventricle (taken at transplant,
      New York Heart Association class IV), the abundance of the 56-kDa protein
      increased 1.4-fold, and the 51-kDa protein increased 4.3-fold versus nonfailing
      left ventricle (donor hearts). We conclude that (1) multiple UT-A proteins are
      detected in rat and human heart; (2) the 56-kDa protein is upregulated in rat
      heart in uremia or models of hypertension; and (3) the rat results can be
      extended to human heart, where 56- and 51-kDa proteins are increased during heart
      failure.

PMID- 11463721
TI  - High glucose impairs voltage-gated K(+) channel current in rat small coronary
      arteries.
AB  - Hyperglycemia is associated with impaired endothelium-dependent dilation that is
      due to quenching of NO by superoxide (O(2)(. -)). In small coronary arteries
      (CAs), dilation depends more on smooth muscle hyperpolarization, such as that
      mediated by voltage-gated K(+) (Kv) channels. We determined whether high glucose
      enhances O(2)(.-) production and reduces microvascular Kv channel current and
      functional responses. CAs from Sprague-Dawley rats were incubated 24 hours in
      medium containing either normal glucose (NG, 5.5 mmol/L D-glucose), high glucose
      (HG, 23 mmol/L D-glucose), or L-glucose (LG, 5.5 mmol/L D-glucose and 17 mmol/L L
      glucose). O(2)(.-) production was increased in HG arteries. Whole-cell patch
      clamping showed a reduction of 4-aminopyridine (4-AP)-sensitive current (Kv
      current) from smooth muscle cells of HG CAs versus NG CAs or versus LG CAs (peak
      density was 9.95+/-5.3 pA/pF for HG versus 27.8+/-6.8 pA/pF for NG and 28.5+/-5.2
      pA/pF for LG; P<0.05). O(2)(.-) generation (xanthine+xanthine oxidase) decreased
      K(+) current density, with no further reduction by 4-AP. Partial restoration was
      observed with superoxide dismutase and catalase. Constriction to 3 mmol/L 4-AP
      was reduced in vessels exposed to HG (13+/-5%, P<0.05) versus NG (30+/-7%) or LG
      (34+/-4%). Responses to KCl and nifedipine were not different among groups.
      Superoxide dismutase and catalase increased contraction to 4-AP in HG CAs. This
      is the first direct evidence that exposure of CAs to HG impairs Kv channel
      activity. We speculate that this O(2)(.-)-induced impairment may reduce
      vasodilator responsiveness in the coronary circulation of subjects with coronary
      disease or its risk factors.

PMID- 11463722
TI  - Energetic crosstalk between organelles: architectural integration of energy
      production and utilization.
AB  - Cells with high and fluctuating energy demands such as cardiomyocytes need
      efficient systems to link energy production to energy utilization. This is
      achieved in part by compartmentalized energy transfer enzymes such as creatine
      kinase (CK). However, hearts from CK-deficient mice develop normal cardiac
      function under conditions of moderate workload. We have therefore investigated
      whether a direct functional interplay exists between mitochondria and
      sarcoplasmic reticulum or between mitochondria and myofilaments in cardiac cells
      that catalyzes direct energy and signal channeling between organelles. We used
      the selective permeabilization of sarcolemmal membranes with saponin to study the
      functional interactions between organelles within the cellular architecture. We
      measured contractile kinetics, oxygen consumption, and caffeine-induced tension
      transients. The results show that in hearts of normal mice, ATP produced by
      mitochondria (supplied with substrates, oxygen, and adenine nucleotides) was able
      to sustain calcium uptake and contractile speed. Moreover, direct mitochondrially
      supplied ATP was nearly as effective as CK-supplied ATP and much more effective
      than externally supplied ATP, suggesting that a direct ATP/ADP channeling exists
      between the sites of energy production (mitochondria) and energy utilization
      (sarcoplasmic reticulum and myofilaments). On the other hand, in cardiac cells of
      mice deficient in mitochondrial and cytosolic CK, marked cytoarchitectural
      modifications were observed, and direct adenine nucleotide channeling between
      mitochondria and organelles was still effective for sarcoplasmic reticulum and
      myofilaments. Such direct crosstalk between organelles may explain the preserved
      cardiac function of CK-deficient mice under moderate workloads.

PMID- 11463723
TI  - Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for
      SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+)
      handling capacity.
AB  - Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a
      pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level.
      SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+)
      transients; however, the cellular mechanisms underlying altered Ca(2+) handling
      in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal
      microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and
      structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load
      measurements revealed that TG myocytes have significantly enhanced SR Ca(2+)
      load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an
      increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine
      receptor binding activity was decreased by approximately 30%. However, TG
      myocytes had a greater rate of spontaneous ryanodine receptor opening as measured
      by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by
      approximately 50%, whereas the time course of inactivation was unchanged in TG
      myocytes. These studies provide important evidence that SERCA1a can substitute
      both structurally and functionally for SERCA2a in the heart and that SERCA1a
      overexpression can be used to enhance SR Ca(2+) transport and cardiac
      contractility.

PMID- 11463724
TI  - Cardiac-specific expression of heme oxygenase-1 protects against ischemia and
      reperfusion injury in transgenic mice.
AB  - Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon monoxide
      and antioxidant bilirubin. We have previously shown that in response to hypoxia,
      HO-1-null mice develop infarcts in the right ventricle of their hearts and that
      their cardiomyocytes are damaged by oxidative stress. To test whether HO-1
      protects against oxidative injury in the heart, we generated cardiac-specific
      transgenic mice overexpressing different levels of HO-1. By use of a Langendorff
      preparation, hearts from transgenic mice showed improved recovery of contractile
      performance during reperfusion after ischemia in an HO-1 dose-dependent manner.
      In vivo, myocardial ischemia and reperfusion experiments showed that infarct size
      was only 14.7% of the area at risk in transgenic mice compared with 56.5% in wild
      type mice. Hearts from these transgenic animals had reduced inflammatory cell
      infiltration and oxidative damage. Our data demonstrate that overexpression of HO
      1 in the cardiomyocyte protects against ischemia and reperfusion injury, thus
      improving the recovery of cardiac function.

PMID- 11463725
TI  - Impaired hyperpolarization in regenerated endothelium after balloon catheter
      injury.
AB  - Ca(2+)-activated K(+) (K(Ca)) channels control endothelial Ca(2+) homeostasis and
      the formation of vasodilators. After angioplasty, dysfunction of the regenerated
      endothelium leads to abnormal vasoregulation. In this study, we tested the
      expression and function of K(Ca) channels in regenerated endothelium at 6 weeks
      after balloon catheter injury of rat carotid arteries (CAs) by using single-cell
      reverse transcription-polymerase chain reaction, patch-clamp techniques, and
      analysis of vasoreactivity. In single regenerated endothelial cells (ECs), the
      percentage of ECs expressing the K(Ca) genes, rSK3 (12+/-8%) and rIK1 (22+/-9%),
      was significantly lower compared with the percentage of native ECs expressing
      these genes (rSK3 58+/-8%, rIK1 64+/-10%). In patch-clamp experiments, K(Ca)
      currents and acetylcholine-induced hyperpolarization were markedly reduced in
      regenerated ECs (shift of membrane potential -6+/-3 mV) compared with those in
      native ECs (shift of membrane potential -21+/-5 mV). In pressure myograph
      experiments, acetylcholine-induced dilation was impaired in reendothelialized CAs
      compared with normal CAs. Intraluminal application of the K(Ca) blocker apamin
      and charybdotoxin inhibited dilation by 30% in normal CAs but was without effect
      in reendothelialized CAs. Intraluminal application of 1-ethyl-2-benzimidazolinone
      (100 micromol/L), an opener of K(Ca) channels, evoked dilation by 29% in normal
      CAs but had no effect in reendothelialized CAs. In conclusion, the impaired
      expression of K(Ca) channels in regenerated endothelium results in defective
      hyperpolarization and impaired dilation. Thus, the impaired K(Ca) channel
      function contributes to functional alterations of regenerated endothelium after
      angioplasty.

PMID- 11463726
TI  - Smooth muscle cell changes during flow-related remodeling of rat mesenteric
      resistance arteries.
AB  - To obtain information on the molecular and cellular mechanisms of flow-induced
      arterial remodeling, we analyzed the morphology and smooth muscle cell (SMC)
      characteristics in rat mesenteric resistance arteries after interventions that
      decreased and increased flow. Juvenile male Wistar Kyoto rats were subjected to
      surgery that, compared with control arteries, provided arteries with chronic low
      flow and chronic high flow. Low flow resulted in a decreased passive lumen
      diameter, hypotrophy of the artery wall, and both loss and decreased size of
      SMCs. Time course studies, with intervention length ranging from 2 to 32 days of
      altered blood flow, showed that the narrowing of the lumen diameter in low-flow
      arteries appeared within 2 days and that an early dedifferentiation of SMC
      phenotype was indicated by markedly reduced levels of desmin mRNA. High flow
      resulted in an increased passive lumen diameter and in hypertrophy of the artery
      wall. The hypertrophy resulted from SMC proliferation because SMC number,
      measured by the 3D-dissector technique, was increased and immunohistochemical
      assessment of proliferating cell nuclear antigen also showed an increase. The
      widening of high-flow arteries required 16 days to become established, at which
      time desmin mRNA was reduced. This time was also required to establish changed
      wall mass in both low-flow and high-flow arteries. Apoptotic cells detected by
      TdT-mediated dUTP-biotin nick end labeling staining were mainly located in the
      medial layer, and evaluation of DNA fragmentation indicated that increased
      apoptosis occurred in both low flow and high flow. This study shows for the first
      time direct evidence that reduced and elevated blood flow in resistance arteries
      produce, respectively, decrease and increase in SMC number, with
      dedifferentiation of the SMCs in both cases.

PMID- 11463727
TI  - Investigation of relationship between reduced, oxidized, and protein-bound
      homocysteine and vascular endothelial function in healthy human subjects.
AB  - Previous studies investigating homocysteine and vascular disease have relied on
      total plasma homocysteine as the sole index of homocysteine status. We examined
      the dynamic relationship between vascular endothelial function and concentrations
      of total, protein-bound oxidized, free oxidized, and reduced homocysteine to
      identify the homocysteine form associated with endothelial dysfunction in humans.
      We investigated 14 healthy volunteers (10 men, 4 women). Brachial artery flow
      mediated dilatation was measured at baseline and at 30, 60, 120, 240, and 360
      minutes after oral (1) L-methionine (50 mg/kg), (2) L-homocysteine (5 mg/kg), and
      (3) placebo. Plasma concentrations of total, protein-bound oxidized, free
      oxidized, and reduced homocysteine were measured at each time point, and
      nitroglycerin-induced dilatation at was assessed at 0, 120, and 360 minutes. Flow
      mediated dilatation fell, and concentrations of total, protein-bound oxidized,
      free oxidized, and reduced homocysteine increased after oral homocysteine and
      oral methionine (all P<0.05 for difference in time course compared with placebo).
      Flow-mediated dilatation showed a reciprocal relationship with reduced
      homocysteine during both homocysteine and methionine loading. In both loading
      studies, peak reduction in flow-mediated dilatation coincided with maximal
      reduced homocysteine concentrations. In contrast, there was no consistent
      relationship between flow-mediated dilatation and free oxidized homocysteine,
      protein-bound oxidized homocysteine, or related species. Nitroglycerin-induced
      dilatation was unchanged by oral homocysteine and oral methionine (P>0.10
      compared with placebo). Reduced homocysteine is closely associated with
      endothelial dysfunction during oral methionine and oral homocysteine loading. Our
      observations support the hypothesis that reduced homocysteine is the deleterious
      form of homocysteine for vascular function in vivo and suggest a less important
      role for other homocysteine species.

PMID- 11463728
TI  - Homozygous SCN5A mutation in long-QT syndrome with functional two-to-one
      atrioventricular block.
AB  - Heterozygous mutations in genes encoding cardiac ionic channel subunits KCNQ1,
      HERG, SCN5A, KCNE1, and KCNE2 are causally involved in the dominant form of long
      QT syndrome (LQTS) while homozygous mutations in KCNQ1 and KCNE1 cause LQTS with
      or without congenital deafness. In addition, two homozygous HERG mutations have
      been associated with severe LQTS with functional atrioventricular conduction
      anomalies in young children. A 2:1 atrioventricular block (AVB) with a major QTc
      prolongation (526 ms) was evidenced in a 5-year-old boy referred for syncope and
      seizure. LQTS was diagnosed and beta-blocking therapy initiated leading to normal
      atrioventricular conduction. Electrophysiological study provided support that
      location of the AVB was infra-Hisian. DNA analysis was performed in the proband
      and in asymptomatic family members. A novel missense mutation, V1777M, in the
      early C-terminal domain of SCN5A was identified. The proband was homozygous while
      the parents and two siblings were heterozygous carriers. Homozygote and
      heterozygote expression of the mutant channels in tsA201 mammalian cells resulted
      in a persistent inward sodium current of 3.96+/-0.83% and 1.49+/-0.47% at -30 mV,
      respectively, which was dramatically reduced in the presence of tetrodotoxin.
      This study provides the first evidence for a homozygous missense mutation in
      SCN5A and suggests that LQTS with functional 2:1 AVB in young children, a severe
      phenotype associated with bad prognosis, may be caused by homozygous or
      heterozygous compound mutations not only in HERG but also in SCN5A. The full text
      of this article is available at http://www.circresaha.org.

PMID- 11463729
TI  - Knowledge is power.

PMID- 11463730
TI  - In silico veritas. Data-mining and automated discovery: the truth is in there.

PMID- 11463731
TI  - Public views on GMOs: deconstructing the myths. Stakeholders in the GMO debate
      often describe public opinion as irrational. But do they really understand the
      public?

PMID- 11463732
TI  - Biological research in Japan and Asia. An interview with Ken-ichi Arai, Dean of
      the Institute of Medical Science at the University of Tokyo and President of the
      Asia-Pacific International Molecular Biology Network.

PMID- 11463733
TI  - They are moving. Germany has started a broad debate about legalising the use of
      surplus embryos for biomedical research.

PMID- 11463734
TI  - Of mice and Mendel. The predicted rise in the use of knock-out and transgenic
      mice should cause us to reflect on our justification for the use of animals in
      research.

PMID- 11463735
TI  - Proteomics: biology in the post-genomic era. Companies all over the world rush to
      lead the way in the new post-genomics race.

PMID- 11463738
TI  - Brakes and gas pedals. Meeting: Spetses 2000, molecular mechanisms of development
      and disease.

PMID- 11463739
TI  - Ion channels in health and disease. 83rd Boehringer Ingelheim Fonds International
      Titisee Conference.

PMID- 11463740
TI  - Sex and sugar in yeast: two distinct GPCR systems.
AB  - Although eukaryotic G-protein coupled receptor (GPCR) systems are well known for
      their ability to detect and mediate rapid responses to extracellular signals, the
      full range of stimuli to which they respond may not yet have been identified.
      Activation of GPCRs by hormones, pheromones, odorants, neurotransmitters, light
      and different taste compounds is well established. However, the recent discovery
      of a glucose-sensing GPCR system in Saccharomyces cerevisiae has unexpectedly
      added common nutrients to this list of stimuli. This GPCR system mediates glucose
      activation of adenylate cyclase during the switch from respirative/gluconeogenic
      metabolism to fermentation. The GPCR system involved in pheromone signalling in
      S. cerevisiae has already served as an important model and tool for the study of
      GPCR systems in higher eukaryotic cell types. Here, we highlight the similarities
      and differences between these two signalling systems. We also indicate how the
      new glucose-sensing system can serve as a model for GPCR function and as a tool
      with which to screen for heterologous components of signalling pathways as well
      as for novel ligands in high-throughput assays.

PMID- 11463741
TI  - Structure--function relationships in HIV-1 Nef.
AB  - The accessory Nef protein of HIV and SIV is essential for viral pathogenesis, yet
      it is perplexing in its multitude of molecular functions. In this review we
      analyse the structure-function relationships of motifs recently proposed to play
      roles in aspects of Nef modification, signalling and trafficking, and thereby to
      impinge on the ability of the virus to survive in, and to manipulate, its
      cellular host. Based on the full-length structure assembly of HIV Nef, we
      correlate surface accessibility with secondary structure elements and sequence
      conservation. Motifs involved in Nef-mediated CD4 and MHC I downregulation are
      located in flexible regions of Nef, suggesting that the formation of the
      transient trafficking complexes involved in these processes depends on the
      recognition of primary sequences. In contrast, the interaction sites for
      signalling molecules that contain SH3 domains or the p21-activated kinases are
      associated with the well folded core domain, suggesting the recognition of highly
      structured protein surfaces.

PMID- 11463742
TI  - A novel stop codon readthrough mechanism produces functional Headcase protein in
      Drosophila trachea.
AB  - Translational regulation provides an efficient means to control the localization
      and production of proteins. The headcase (hdc) mRNA in Drosophila generates two
      overlapping proteins as a result of translational readthrough of an internal UAA
      stop codon. This readthrough event is necessary for the function of hdc as a
      branching inhibitor during tracheal development. By ectopic expression of
      different Hdc proteins in the trachea, we show that the long Hdc form alone, can
      function as a potent branching inhibitor whose activity is proportional to its
      amount. The suppression of termination in the hdc mRNA is not stop-codon
      dependent, suggesting that the readthrough does not involve codon specific
      suppressors. We have identified an 80 nucleotide sequence immediately downstream
      of the UAA, which is necessary and sufficient to confer termination readthrough
      in a heterologous mRNA. We present a novel mechanism of eukaryotic translational
      termination suppression that may regulate the amount of functional Hdc.

PMID- 11463743
TI  - A novel mechanism of matrix metalloproteinase-9 gene expression implies a role
      for keratinization.
AB  - To investigate the pathophysiological role of matrix metalloproteinase (MMP)-9 in
      the skin, we analyzed MMP-9 expression from human keratinocytes in culture. MMP-9
      and the terminal differentiation marker involucrin were co-localized in the same
      keratinocytes with a high concentration of Ca(2+), a potent stimulator of
      differentiation. We identified the novel KRE-M9 element, further downstream to
      the previously reported TPA responsive element in the MMP-9 promoter, and both of
      these two elements were shown to be important for MMP-9 transcription and Ca(2+)
      induction. The concomitant upregulation of MMP-9 and involucrin transcripts was
      probably due to the very similar gene regulatory elements, KRE-M9 and KRE-4, in
      their respective promoters. These results indicate a novel mechanism of
      transcriptional regulation for MMP-9 in the process of keratinization, implying
      the probable association of apoptosis and differentiation of keratinocytes in
      epidermal skin tissue.

PMID- 11463744
TI  - Xenopus FRS2 is involved in early embryogenesis in cooperation with the Src
      family kinase Laloo.
AB  - FRS2 has been identified in mammalian cells as a protein that is tyrosine
      phosphorylated and binds to Grb2 and Shp2 in response to fibroblast growth factor
      (FGF) or nerve growth factor (NGF) stimulation. But neither its existence in
      other vertebrate classes or invertebrates nor its function during embryonic
      development has been defined. Here we have identified and characterized a Xenopus
      homolog of FRS2 (xFRS2). xFRS2 is tyrosine phosphorylated in early embryos, and
      overexpression of an unphosphorylatable form of xFRS2 interferes with FGF
      dependent mesoderm formation. The Src family kinase Laloo, which was shown to
      function in FGF signaling during early Xenopus development, binds to xFRS2 and
      promotes tyrosine phosphorylation of xFRS2. Moreover, xFRS2 and Laloo are shown
      to bind to Xenopus FGF receptor 1. These results suggest that xFRS2 plays an
      important role in FGF signaling in cooperation with Laloo during embryonic
      development.

PMID- 11463745
TI  - YidC, an assembly site for polytopic Escherichia coli membrane proteins located
      in immediate proximity to the SecYE translocon and lipids.
AB  - Like its mitochondrial homolog Oxa1p, the inner membrane protein YidC of
      Escherichia coli is involved in the integration of membrane proteins. We have
      analyzed individual insertion steps of the polytopic E. coli membrane protein
      MtlA targeted as ribosome-nascent chain complexes to inner membrane vesicles.
      YidC can accommodate at least the first two transmembrane segments of MtlA at the
      protein lipid interface and retain them even though the length of the nascent
      chain would amply allow insertion into membrane lipids. An even longer insertion
      intermediate of MtlA is described that still has the first transmembrane helix
      bound to YidC while the third contacts SecE and YidC during integration. Our
      findings suggest that YidC forms a contiguous integration unit with the SecYE
      translocon and functions as an assembly site for polytopic membrane proteins
      mediating the formation of helix bundles prior to their release into the membrane
      lipids.

PMID- 11463746
TI  - CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri.
AB  - Epithelial cells are refractory to extracellular lipopolysaccharide (LPS), yet
      when presented inside the cell, it is capable of initiating an inflammatory
      response. Using invasive Shigella flexneri to deliver LPS into the cytosol, we
      examined how this factor, once intracellular, activates both NF-kappaB and c-Jun
      N-terminal kinase (JNK). Surprisingly, the mode of activation is distinct from
      that induced by toll-like receptors (TLRs), which mediate LPS responsiveness from
      the outside-in. Instead, our findings demonstrate that this response is mediated
      by a cytosolic, plant disease resistance-like protein called CARD4/Nod1.
      Biochemical studies reveal enhanced oligomerization of CARD4 upon S. flexneri
      infection, an event necessary for NF-kappaB induction. Dominant-negative versions
      of CARD4 block activation of NF-kappaB and JNK by S. flexneri as well as
      microinjected LPS. Finally, we showed that invasive S. flexneri triggers the
      formation of a transient complex involving CARD4, RICK and the IKK complex. This
      study demonstrates that in addition to the extracellular LPS sensing system
      mediated by TLRs, mammalian cells also possess a cytoplasmic means of LPS
      detection via a molecule that is related to plant disease-resistance proteins.

PMID- 11463747
TI  - Stop codon recognition in ciliates: Euplotes release factor does not respond to
      reassigned UGA codon.
AB  - In eukaryotes, the polypeptide release factor 1 (eRF1) is involved in translation
      termination at all three stop codons. However, the mechanism for decoding stop
      codons remains unknown. A direct interaction of eRF1 with the stop codons has
      been postulated. Recent studies focus on eRF1 from ciliates in which some stop
      codons are reassigned to sense codons. Using an in vitro assay based on mammalian
      ribosomes, we show that eRF1 from the ciliate Euplotes aediculatus responds to
      UAA and UAG as stop codons and lacks the capacity to decipher the UGA codon,
      which encodes cysteine in this organism. This result strongly suggests that in
      ciliates with variant genetic codes eRF1 does not recognize the reassigned
      codons. Recent hypotheses describing stop codon discrimination by eRF1 are not
      fully consistent with the set of eRF1 sequences available so far and require
      direct experimental testing.

PMID- 11463748
TI  - FRET-based detection of different conformations of MK2.
AB  - MAP kinase-activated protein kinase 2 (MK2 or MAPKAP K2) is a stress-activated
      enzyme downstream to p38 MAPK. By fusion of green fluorescent protein variants to
      the N- and C-terminus we analysed conformational changes in the kinase molecule
      in vitro and in vivo. Activation of MK2 is accompanied by a decrease in
      fluorescence resonance energy transfer, indicating a transition from an
      inactive/closed to an active/open conformation with an increase in the apparent
      distance between the fluorophores of approximately 9 A. The closed conformation
      exists exclusively in the nucleus. Upon stress, the open conformation of MK2
      rapidly becomes detectable in the cytoplasm and accumulates in the nucleus only
      when Crm1-dependent nuclear export is blocked. Hence, in living cells activation
      of MK2 and its nuclear export are coupled by a phosphorylation-dependent
      conformational switch.

PMID- 11463749
TI  - Specific polar localization of ribosomes in Bacillus subtilis depends on active
      transcription.
AB  - The large subunit of ribosomes in Bacillus subtilis was tagged by generation of a
      fusion of ribosomal protein L1 to blue fluorescent protein (BFP). The fusion was
      fully active and localized around the nucleoids, predominantly close to the cell
      poles, in growing cells. However, in stationary phase cells, and in growing cells
      treated with rifampicin, L1-BFP was distributed throughout the cells, in contrast
      to cells treated with chloramphenicol, in which ribosomes still localized around
      nucleoids. These data show that specific localization of ribosomes is not due to
      nucleoid exclusion, but is a dynamic process due to active synthesis of RNA. Dual
      labelling of ribosomes and cold shock proteins (CSPs) tagged with green
      fluorescent protein (GFP) revealed colocalization of both protein classes. CSPs
      are implicated in coupling of transcription with translation and may bridge the
      spatial separation of ribosomes and nucleoid-associated RNA polymerase.

PMID- 11463750
TI  - Studies in hemodynamics and hypertension.
AB  - This review covers a representative sampling of investigations in hemodynamics
      and hypertension performed by the author during the period from approximately
      1945 to 1980. The hemodynamic studies included a description of changes
      associated with congestive heart failure and with acute myocardial infarction.
      These studies emphasized for the first time the importance of left ventricular
      afterload and of the mobilizable venous reservoir. Other hemodynamic studies
      included diverse subjects such as the first and only recordings of pulse waves in
      arteries as small as 200 gammam in diameter, velocity differences between red
      blood cells and plasma, turbulent blood flow in the ascending aorta, increase in
      velocity of blood flow of leg veins under compression, rates of transcapillary
      flow of solutes in humans, and the first use of external arterial pulse wave
      recordings to assess vascular compliance. Pioneer studies in hypertension
      included the first use of an antihypertensive drug to treat malignant
      hypertension and the first report of the treatment of hypertension with a
      thiazide diuretic.

PMID- 11463751
TI  - 6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic
      localization of pheochromocytoma.
AB  - The diagnosis and treatment of pheochromocytoma depend critically on effective
      means to localize the tumor. Computed tomography and magnetic resonance imaging
      have good sensitivity but poor specificity for detecting pheochromocytoma, and
      nuclear imaging approaches such as (131)I-metaiodobenzylguanidine scintigraphy
      have limited sensitivity. Here we report initial results using 6
      [(18)F]fluorodopamine positron emission tomography (PET) scanning in the
      diagnostic localization of pheochromocytoma. Twenty-eight patients with known or
      clinically suspected pheochromocytoma underwent PET scanning after intravenous
      injection of 6-[(18)F]fluorodopamine. Of the 28 patients, 9 had surgical
      confirmation of the tumor, 8 had previously diagnosed metastatic
      pheochromocytoma, and 11 had plasma levels of metanephrines that were within
      normal limits. All 9 patients with surgically proven pheochromocytoma had
      abnormal 6-[(18)F]fluorodopamine PET scans that identified the tumors. All 8
      patients with metastatic pheochromocytoma had extra-adrenal sites of 6
      [(18)F]fluorodopamine-derived activity. Of the 11 patients with normal plasma
      levels of metanephrines, 9 had negative 6-[(18)F]fluorodopamine PET scans, 1 had
      extra-adrenal foci of 6-[(18)F]fluorodopamine-derived activity, and 1 had
      symmetric uptake of 6-[(18)F]fluorodopamine in the region of the adrenal glands.
      In patients with known disease, 6-[(18)F]fluorodopamine PET scanning can detect
      and localize pheochromocytomas with high sensitivity. In patients in whom the
      diagnosis of pheochromocytoma is considered but excluded because of negative
      plasma metanephrine results, 6-[(18)F]fluorodopamine PET scans are consistently
      negative. These findings justify a clinical trial of 6-[(18)F]fluorodopamine PET
      scanning as a diagnostic tool.

PMID- 11463752
TI  - Microsatellite DNA polymorphism of human adrenomedullin gene in normotensive
      subjects and patients with essential hypertension.
AB  - Adrenomedullin (AM) is a hypotensive peptide widely produced in the
      cardiovascular organs and tissues. We have cloned and sequenced the genomic DNA
      encoding the human AM gene and have determined that the gene is located in the
      short arm of chromosome 11. The 3'-end of the gene is flanked by the
      microsatellite marker of cytosine adenine (CA) repeats. In this study, we
      investigated the association between DNA variations in AM gene and the
      predisposition to hypertension. Genomic DNA was obtained from 272 healthy
      normotensive subjects (NT) age 57+/-5 years and 266 patients with essential
      hypertension (EH) age 53+/-11 years. The DNA was subject to PCR using a
      fluorescence-labeled primer, and the number of CA repeats were determined by poly
      acrylamide gel electrophoresis. The averaged blood pressure was 117+/-13/73+/-9
      mm Hg in NT and 170+/-23/104+/-12 mm Hg in EH. In Japanese, there existed 4 types
      of alleles with different CA-repeat numbers: 11, 13, 14, and 19. The frequencies
      of these alleles were significantly different between NT and EH (chi(2)=9.43,
      P=0.024). Namely, 13.5% of EH carried the 19-repeat allele, whereas the frequency
      was 6.2% in NT (chi(2)=7.62, P=0.007). In NT, plasma AM concentrations were not
      significantly different between the genotypes. In conclusion, microsatellite DNA
      polymorphism of AM gene may be associated with the genetic predisposition to EH,
      although the gene expression is not likely to be affected by the genotypes.

PMID- 11463753
TI  - Link of nonhemodynamic factors to hemodynamic determinants of left ventricular
      hypertrophy.
AB  - Despite current evidence suggesting that hemodynamic load is the fundamental
      stimulus to begin the sequence of biological events leading to the development of
      left ventricular hypertrophy, genotype, gender, body size, and less easily
      recognizable environmental factors may contribute to generate the cascade of
      molecular changes that eventually yield the increase in protein synthesis needed
      to increase left ventricular mass. However, even nonhemodynamic factors such as
      gender and body size eventually regulate the growth of left ventricular mass by
      at least in part influencing loading conditions. Consideration of measurable
      factors, such as gender, body size, and hemodynamic load, allows evaluation of
      individual echocardiographic left ventricular mass as the deviation from the
      level that would be required to face a gender-specific hemodynamic load at a
      given body size. Values of left ventricular mass that are inappropriately high
      for individual gender, body size, and hemodynamic load are associated with a high
      cardiovascular risk phenotype, even independent of the presence of arterial
      hypertension. Thus, the condition of inappropriately high left ventricular mass
      may be recognized as a more advanced stage of pathological structural changes
      initially induced by overload, going beyond the compensatory needs. The
      biological process that yields inappropriate left ventricular mass is probably
      linked to the protracted activity over time of biological mediators of left
      ventricular hypertrophy, such as proto-oncogenes and other growth factors,
      neurohormones, and cytokines, inducing structural modifications that initially
      compensate imposed overload but eventually change the structure of myocardial
      tissue and the composition of motor units.

PMID- 11463754
TI  - Hypertension in an anthropological and evolutionary paradigm.

PMID- 11463755
TI  - Prostaglandin I(2)/E(2) ratios in unilateral renovascular hypertension of
      different severities.
AB  - Differences between prostaglandins I(2) and E(2) in their renal synthesis and
      pathophysiological roles were investigated in unilateral renovascular
      hypertension of different severities in 18 patients: 6 with mild stenosis (<75%
      of the diameter) of the renal artery, 7 with moderate stenosis (75% to 90%), and
      5 with severe stenosis (>90%). Before and after aspirin administration (10
      mg/kg), renal venous and aortic plasma was assayed for 6-ketoprostaglandin
      F(1alpha) (instead of prostaglandin I(2)), prostaglandin E(2), and renin
      activity. In mild or moderate stenosis, the mean 6-ketoprostaglandin F(1alpha)
      level in renal venous plasma from the stenotic side was not different from that
      from the normal side or from aortic plasma. Prostaglandin E(2) levels and renin
      activity in such patients were higher on the stenotic side than on the normal
      side and higher in venous than in aortic plasma. Aspirin inhibited prostaglandin
      E(2) synthesis and suppressed renin release from stenotic kidneys and lowered
      blood pressure as the renin activity decreased in patients with mild or moderate
      stenosis. In severe stenosis, levels of 6-ketoprostaglandin F(1alpha) and
      prostaglandin E(2) were higher on the stenotic side than on the normal side and
      higher in venous than in aortic plasma. Aspirin inhibited the synthesis of both
      prostaglandins and suppressed renin release from the stenotic kidney. In patients
      with unilateral renovascular hypertension with mild or moderate stenosis of the
      renal artery, prostaglandin E(2), rather than I(2), seems to contribute to
      further acceleration of renin release. Prostaglandin I(2) may increase and
      participate in further renin release when the stenosis is severe.

PMID- 11463756
TI  - Genomic scan for exercise blood pressure in the Health, Risk Factors, Exercise
      Training and Genetics (HERITAGE) Family Study.
AB  - Agenome-wide linkage scan was performed for genes affecting submaximal exercise
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the sedentary
      state and their responses to a standardized endurance training program. A total
      of 344 polymorphic markers were used, and 344 pairs of siblings from 99 white
      nuclear families and 102 sibling pairs from 105 black family units were available
      for the study. All subjects were healthy but sedentary at baseline. SBP and DBP
      were measured during exercise tests at 2 different intensities: 50 W (SBP50 and
      DBP50) and 80% of maximal oxygen consumption (SBP80 and DBP80). Baseline blood
      pressure phenotypes were adjusted for age, gender, and body mass index, and the
      training responses (after training minus baseline [Delta]) were adjusted for age,
      gender, baseline body mass index, and baseline blood pressure. Two analytical
      strategies were used: a multipoint variance-components linkage analysis using all
      the family data and a single-point linkage analysis using pairs of siblings. In
      whites, promising linkages (lod score >1.75) were detected for baseline SBP80 on
      10q23-q24 and for DeltaSBP50 on 8q21. In addition, several chromosomal regions
      with suggestive evidence of linkage (lod score 1.0 to 1.75) were observed for
      SBP50 (22q11.2-q13), DBP50 (6q23-q27), SBP80 (2p24, 2q21, 14q11.1-q12, and
      16q21), DBP80 (6q13-q21), DeltaSBP50 (7p12-p13), and DeltaDBP50 (5q31-q32). In
      blacks, DBP50, DBP80, and DeltaDBP80 showed promising quantitative trait loci on
      18p11.2, 11q13-q21, and 10q21-q23, respectively. Suggestive linkages were evident
      for DBP50 on 2p22-p25, 11p15.5, and 18q21.1; for SBP80 on 6q21-q21, 6q31-q36,
      12q12-q13, 15q12-q13, and 17q11-q12; and for DBP80 on 8q24, 10q21-q24, and 12p13.
      All the detected chromosomal regions include several potential candidate genes
      and therefore warrant further studies in the Health, Risk Factors, Exercise
      Training and Genetics (HERITAGE) cohort and other studies.

PMID- 11463757
TI  - Peaks and valleys.

PMID- 11463758
TI  - Heritability estimates of obesity measures in siblings with and without
      hypertension.
AB  - The goal of the present study was to evaluate mean values and heritability
      estimates of 3 global and 11 regional obesity measures in siblings with (HPT,
      n=209) or without (non-HPT, n=91) early-onset (age </=55 years) hypertension who
      originated from the same families. Sixty-one sibships, each having at least 2 HPT
      siblings, were selected from a French-Canadian population with a known founder
      effect. Comparison of the mean values showed that HPT siblings are more obese
      than non-HPT siblings and that the body fat of HPT siblings is more centrally
      distributed. Significant differences were observed in all global obesity measures
      (P=0.009 to 0.0001). Among the regional measures, the most prominent differences
      were seen in waist circumference (P=0.00002), waist/hip ratio (P=0.0001), and
      suprailiac skinfold (P=0.00008). Comparison of the heritability estimates derived
      from sibling/sibling correlations (FCOR program, SAGE) suggested that genetic
      factors play a greater role in HPT (n=357) than in non-HPT (n=93) sib-pairs in
      determining most obesity measures. Similar to the mean values, these differences
      were most apparent in global and upper-body measures, with heritabilities ranging
      from 40% to 70% (P=0.05 to 0.0006) in HPT siblings and from 0% to 32% (P=NS) in
      non-HPT siblings. In summary, the present results suggest that HPT and non-HPT
      siblings drawn from the same families differ by the degree and distribution of
      body fat accumulation and that this difference is determined, at least in part,
      by genetic factors cosegregating with hypertension. This, in turn, suggests that
      a genetic link exists between obesity and hypertension in these families.

PMID- 11463759
TI  - Endothelial apoptosis induced by oxidative stress through activation of NF
      kappaB: antiapoptotic effect of antioxidant agents on endothelial cells.
AB  - Injury of endothelial cells has been assumed to be an initial trigger of the
      development of atherosclerosis. In this study, we investigated the molecular
      mechanisms of endothelial cell death induced by hypoxia, which leads to oxidative
      stress. To study the relation between hypoxia-induced cell death and activation
      of nuclear factor-kappaB (NF-kappaB) in a hypoxic state, we evaluated the effect
      of 2 antioxidant drugs, probucol and pyrrolidine dithiocarbamate (PDTC), on human
      endothelial apoptosis. Although hypoxic treatment of human aortic endothelial
      cells resulted in a significant decrease in cell number and a significant
      increase in apoptotic cells compared with that of cells under normoxia (P<0.01),
      treatment with probucol (50 micromol/L) or PDTC (100 micromol/L) significantly
      attenuated the decrease in cell number (P<0.01) and was accompanied by inhibition
      of NF-kappaB activation. Furthermore, downregulation of bcl-2 caused by hypoxia
      was inhibited by these drugs. We further investigated the translocation of bax
      protein from the cytoplasm to the mitochondrial heavy fraction membrane, as
      translocation of bax protein is considered to be a determinant of apoptosis.
      Interestingly, we found that antioxidant treatment inhibited the translocation of
      bax protein caused by hypoxia. Moreover, upregulation of p53, a proapoptotic
      molecule, was observed in hypoxia, whereas treatment with probucol attenuated the
      expression of p53 accompanied by suppression of NF-kappaB activation. These data
      suggest functional links between p53 and endothelial apoptosis through the
      activation of NF-kappaB. Overall, the current study demonstrated that oxidative
      stress induced apoptosis in human aortic endothelial cells through the
      downregulation of bcl-2, translocation of bax, and upregulation of p53, probably
      through NF-kappaB activation. Oxidative stress may play an important role in
      endothelial apoptosis mediated by hypoxia, through the activation of NF-kappaB.

PMID- 11463760
TI  - Src is an important mediator of extracellular signal-regulated kinase 1/2
      dependent growth signaling by angiotensin II in smooth muscle cells from
      resistance arteries of hypertensive patients.
AB  - The role of c-Src in growth signaling by angiotensin (Ang) II was investigated in
      vascular smooth muscle cells (VSMCs) from arteries of hypertensive patients. c
      Src and extracellular signal-regulated kinase 1/2 (ERK1/2) activity, proto
      oncogene expression, activating protein-1 (AP-1) DNA-binding activity, and DNA
      and protein synthesis were studied in Ang II-stimulated VSMCs derived from small
      peripheral resistance arteries of normotensive subjects (NTs, n=5) and age
      matched untreated hypertensive patients (HTs, n=10). Ang II type 1 (AT(1)) and
      type 2 (AT(2)) receptor status was also assessed. Ang II dose-dependently
      increased the synthesis of DNA and protein, with enhanced effects in VSMCs from
      HTs. PD 098,059, a selective inhibitor of the ERK1/2 pathway, attenuated Ang II
      stimulated growth in HTs. The effects of PD 098,059 were greater in HTs than in
      NTs. In NTs, Ang II transiently increased ERK1/2 phosphorylation, whereas in HTs,
      Ang II-stimulated actions were augmented and sustained. PP2, a selective Src
      inhibitor, reduced ERK1/2 activity and normalized ERK1/2 responses in HTs. Ang II
      induced c-Src phosphorylation was 2- to 3-fold greater in HTs than in NTs. In HTs
      but not NTs, kinase activation was followed by overexpression of c-fos and
      enhanced AP-1 DNA-binding activity. PD 098,059 and PP2 attenuated these
      responses. AT(1) receptor expression was similar in NTs and HTs. In HT cells
      transfected with c-fos antisense oligodeoxynucleotide, Ang II-stimulated growth
      was reduced compared with sense oligodeoxynucleotide. Our findings suggest that
      augmented Ang II-stimulated VSMC growth is mediated via hyperactivation of c-Src
      regulated ERK1/2-dependent pathways, leading to overexpression of c-fos mRNA and
      enhanced AP-1 DNA-binding activity. Because AT(1) receptor expression was
      unaltered in HTs, increased Ang II signaling may be a postreceptor phenomenon.
      These data define a signal transduction pathway whereby Ang II mediates
      exaggerated growth in VSMCs from HTs.

PMID- 11463761
TI  - Analysis of cell-specific promoters for viral gene therapy targeted at the
      vascular endothelium.
AB  - The use of viral vectors for vascular gene therapy targeted at the endothelium is
      limited by the promiscuous tropism of vectors and nonspecificity of viral
      promoters, resulting in high-level transgene expression in multiple tissues. To
      evaluate suitable endothelial cell (EC)-specific promoters for vascular gene
      therapy, we directly compared the ability of the fms-like tyrosine kinase-1 (FLT
      1), intercellular adhesion molecule-2 (ICAM-2), and von Willebrand factor (vWF)
      promoters to drive EC-restricted transcription after cloning into adenoviral
      vectors upstream of lacZ. Vastly different expression profiles were observed.
      Whereas both FLT-1 and ICAM-2 promoters generated transgene expression levels
      similar to cytomegalovirus in ECs in vitro, vWF expression levels were extremely
      low. Analysis of non-EC types revealed that ICAM-2 but not FLT-1 evoked leaky
      transgene expression, thus identifying FLT-1 as the most selective promoter. With
      an ex vivo human gene therapy model, the FLT-1 promoter demonstrated EC-specific
      transgene expression in intact human vein but no detectable expression from
      infected exposed smooth muscle cells in EC-denuded vein. Furthermore, when
      adenoviruses were systemically administered to mice, the FLT-1 promoter
      demonstrated extremely low-level gene expression in the liver, the major target
      organ for adenoviral transduction in vivo. This study highlights the potential of
      using the FLT-1 promoter for local and systemic human gene therapy in
      hypertension and its complications.

PMID- 11463762
TI  - Perceived job stress but not individual cardiovascular reactivity to stress is
      related to higher blood pressure at work.
AB  - Psychological stress has been reported to be related to higher blood pressure
      (BP) and unfavorable cardiovascular profile. However, because of the complexity
      of personal stress management, a multilevel stress measurement strategy is
      needed. The aim of this cross-sectional study was to analyze the respective
      influences of the subjective perception of professional strain (high demand and
      low latitude) and cardiovascular reactivity to a stress test (Stroop stress test)
      on BP. Worksite BP was measured in 303 healthy normotensive subjects, 18 to 55
      years of age, who worked in the same chemical company. In a subset of 70 randomly
      selected subjects, 24-hour ambulatory BP was performed to assess BP during
      working hours. The 20% of subjects who reported the highest job strain (high
      strain group) or the highest BP stress reactivity (high-responder group) were
      compared with the remaining subjects (80%) (non-high-strain or low-responder
      groups). Subjects who submitted to the highest job strain had significantly
      higher ambulatory diastolic BP (4.5 mm Hg, P=0.015) during only working hours,
      whereas BP was similar during the remaining hours. Worksite BP and stress
      cardiovascular reactivity were similar between job strain groups. BP stress
      reactivity did not influence worksite and ambulatory BP. Spontaneous BP
      variability assessed by standard deviation and spectral analysis was equivalent
      between complementary groups. Prevalence of microalbuminuria was significantly
      higher in the high-responder group (8.2% versus 2.5% in low responders) and only
      slightly higher in the high-strain group (6.2% versus 3.2% in non-high strain).
      Potential confounding factors, such as age, gender, alcohol consumption, salt
      intake, body mass index, and occupation, which were equivalent between groups,
      did not interfere with our results. Our study quantifies high-professional strain
      effects on BP levels that appear to be higher only during the working period and
      to be independent from spontaneous BP variability and stress BP reactivity.

PMID- 11463763
TI  - Transepithelial sodium absorption is increased in people of African origin.
AB  - Salt-sensitive hypertension is more common and has more severe consequences in
      urban black populations than in white populations. Increased renal sodium
      reabsorption through epithelial sodium channels may underlie the development of
      high blood pressure in black people. Increased sodium channel activity has been
      detected in subjects with Liddle's syndrome by nasal potential difference
      measurements. Nasal potential difference measurements were made in 39 black
      normotensive, 106 black hypertensive, 51 white normotensive, and 61 white
      hypertensive subjects. Blood pressure, body mass index, and 24-hour urinary
      sodium excretion were also measured. Maximum potential difference was
      significantly higher in black subjects than in white subjects (P=0.009) but was
      not significantly different between normotensive and hypertensive subjects after
      adjustment for age, gender, current smoking status, body mass index, and 24-hour
      urinary sodium excretion (black normotensive, -21.6+/-1.0 mV; black hypertensive,
      -21.5+/-0.7 mV; white normotensive, -18.5+/-1.0 mV; and white hypertensive
      subjects, -18.9+/-0.9 mV). Nasal potential difference did not correlate with
      blood pressure or biochemical variables within ethnic and blood pressure groups.
      Nasal potential difference, an index of nasal sodium channel activity, is greater
      in black than in white people but does not differ between normotensive and
      hypertensive groups. Increased nasal potential difference measurements may
      reflect generalized upregulation of sodium transport in black people compared
      with white people, which may help to explain the high prevalence of hypertension
      in black people but would not explain differences in blood pressure within
      separate ethnic groups.

PMID- 11463764
TI  - Sodium sensitivity of blood pressure appearing before hypertension and related to
      histological damage in immunoglobulin a nephropathy.
AB  - Patients with renal parenchymal disease exhibit sodium-sensitive hypertension. We
      examined patients with immunoglobulin A (IgA) nephropathy to determine whether
      this sensitivity appears before hypertension begins and whether this sensitivity
      is related to histological damage. Thirty-eight patients with IgA nephropathy
      followed a diet with an ordinary sodium level for 1 week and a sodium-restricted
      diet for 1 week, in random order, and were divided into 3 groups by their
      systemic blood pressure on the diet with an ordinary sodium level (optimal,
      <120/<80 mm Hg, n=15; normal to high-normal, 120 to 139/80 to 89 mm Hg, n=18;
      hypertensive, >/=140/>/=90 mm Hg, n=5). The sodium sensitivity index was
      calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn
      by linkage of 2 datum points obtained during the different diets. The scores for
      glomerulosclerosis and tubulointerstitial damage were evaluated
      semiquantitatively. The sensitivity index, glomerulosclerosis score, and score
      for tubulointerstitial damage were higher in patients with normal to high-normal
      blood pressure or hypertension than in patients with optimal pressure. The
      sensitivity index was significantly correlated with glomerulosclerosis (P=0.001)
      and tubulointerstitial damage (P=0.002). In patients with normal to high-normal
      pressure, sodium restriction lowered blood pressure to the optimal range and
      decreased proteinuria. In patients with IgA nephropathy, sodium sensitivity of
      blood pressure related to renal histological damage appears before hypertension.

PMID- 11463765
TI  - Association of sodium channel gamma-subunit promoter variant with blood pressure.
AB  - The SCNN1G gene, located on human chromosome 16p12, encodes the gamma subunit of
      the amiloride-sensitive epithelial sodium channel, and mutations in SCNN1G can
      result in Liddle's syndrome or pseudohypoaldosteronism type I. We identified
      sequence variations in the promoter region of SCNN1G and examined the association
      between this polymorphism and blood pressure in a large cohort (n=4075)
      representing the general population in Japan. We found T(-1290)C, T(-501)G, G(
      173)A, and G(-104)T polymorphisms in the promoter region of SCNN1G and confirmed
      the existence of T387C and T474C polymorphisms in exon 3 and the C1947G
      polymorphism in exon 13. Because the genotypes of the T(-1290)C, T(-501)G, G(
      104)T, and T474C polymorphisms were in tight linkage disequilibrium, we selected
      the T474C and G(-173)A polymorphisms for an association study. The G(-173)A
      polymorphism of SCNN1G had a significant effect on systolic pressure (P=0.0050)
      and pulse pressure (P=0.0050). The AA genotype was associated with an 11 mm Hg
      drop in systolic pressure and an 8 mm Hg drop in pulse pressure and with a higher
      prevalence of hypotension (P=0.0195). A transient transfection assay using MDCK
      cells and human renal epithelial cells indicated that the promoter activity of
      the G(-173) allele was higher than that of the A(-173) allele. Although the
      effects of the A(-173) allele were recessive and although the AA genotype was
      found in just 0.7% of our study population, we observed that this variation of
      human SCNN1G had significant effects on blood pressure.

PMID- 11463766
TI  - Effects of angiotensin-(1-7) on forearm circulation in normotensive subjects and
      patients with essential hypertension.
AB  - Previous animal studies have shown that angiotensin (Ang)-(1-7) is a biologically
      active component of the renin-angiotensin system, acting as a vasoactive agent,
      and may play a role in the blood pressure regulation. There is little
      information, however, on the effect of Ang-(1-7) on human circulation or the
      mechanism of its action. To investigate the effect of Ang-(1-7) on forearm
      circulation and to determine whether this effect is altered in patients with
      essential hypertension, we measured change in forearm blood flow using venous
      occlusion plethysmography in response to intra-arterial infusion of Ang-(1-7)
      (10(-10), 10(-9), and 10(-8) mol/min; for 5 minutes) in normotensive control
      subjects (n=8) and patients with essential hypertension (n=8). Infusion of Ang-(1
      7) significantly increased the forearm blood flow response in a dose-dependent
      manner in both normotensive control subjects (28.7+/-9.7%, at 10(-8) mol/min;
      P<0.05) and hypertensive patients (31.8+/-15.2%, at 10(-8) mol/min; P<0.05). The
      vasodilatory effect of Ang-(1-7) was similar in the two groups. Intra-arterial
      infusion of N(G)-monomethyl-L-arginine, a nitric oxide synthesis inhibitor, did
      not alter the forearm blood flow response to Ang-(1-7) in either group. These
      findings suggest that Ang-(1-7) causes vasodilation in forearm circulation of
      normotensive subjects and patients with essential hypertension through a pathway
      that is independent of nitric oxide synthesis.

PMID- 11463767
TI  - Bradykinin potentiation by angiotensin-(1-7) and ACE inhibitors correlates with
      ACE C- and N-domain blockade.
AB  - ACE inhibitors block B(2) receptor desensitization, thereby potentiating
      bradykinin beyond blocking its hydrolysis. Angiotensin (Ang)-(1-7) also acts as
      an ACE inhibitor and, in addition, may stimulate bradykinin release via
      angiotensin II type 2 receptors. In this study we compared the bradykinin
      potentiating effects of Ang-(1-7), quinaprilat, and captopril. Porcine coronary
      arteries, obtained from 32 pigs, were mounted in organ baths, preconstricted with
      prostaglandin F(2alpha), and exposed to quinaprilat, captopril, Ang-(1-7), and/or
      bradykinin. Bradykinin induced complete relaxation (pEC(50)=8.11+/-0.07, mean+/
      SEM), whereas quinaprilat, captopril, and Ang-(1-7) alone were without effect.
      Quinaprilat shifted the bradykinin curve to the left in a biphasic manner: a 5
      fold shift at concentrations that specifically block the C-domain (0.1 to 1
      nmol/L) and a 10-fold shift at concentrations that block both domains. Captopril
      and Ang-(1-7) monophasically shifted the bradykinin curve to the left, by a
      factor of 10 and 5, respectively. A 5-fold shift was also observed when Ang-(1-7)
      was combined with 0.1 nmol/L quinaprilat. Repeated exposure of porcine coronary
      arteries to 0.1 micromol/L bradykinin induced B(2) receptor desensitization. The
      addition of 10 micromol/L quinaprilat or Ang-(1-7) to the bath, at a time when
      bradykinin alone was no longer able to induce relaxation, fully restored the
      relaxant effects of bradykinin. Angiotensin II type 1 or 2 receptor blockade did
      not affect any of the observed effects of Ang-(1-7). In conclusion, Ang-(1-7),
      like quinaprilat and captopril, potentiates bradykinin by acting as an ACE
      inhibitor. Bradykinin potentiation is maximal when both the ACE C- and N-terminal
      domains are inhibited. The inhibitory effects of Ang-(1-7) are limited to the ACE
      C-domain, raising the possibility that Ang-(1-7) synergistically increases the
      blood pressure-lowering effects of N-domain-specific ACE inhibitors.

PMID- 11463768
TI  - Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1
      expression in rat vascular smooth muscle cells.
AB  - Recently, it was shown that Rho-kinase plays an important role in blood pressure
      regulation. However, it is not known whether Rho-kinase is involved in
      atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important
      chemokine that regulates monocyte recruitment and atherogenesis. Therefore, we
      examined the role of Rho and Rho-kinase in the angiotensin (Ang) II-induced
      expression of MCP-1. Ang II dose- and time-dependently enhanced the expression of
      MCP-1 mRNA and the protein production in vascular smooth muscle cells. CV11974,
      an Ang II type 1 receptor (AT(1)-R) specific antagonist inhibited the enhancement
      of MCP-1 expression by Ang II, suggesting that the effect of Ang II is mediated
      by the AT(1)-R. Botulinum C3 exotoxin, a specific inhibitor of Rho, suppressed
      Ang II-induced MCP-1 production. To examine the role of Rho-kinase in Ang II
      induced MCP-1 expression, we used adenovirus-mediated overexpression of the
      dominant negative mutant of Rho-kinase (AdDNRhoK) or Y-27632, a specific
      inhibitor of Rho-kinase. Both AdDNRhoK and Y-27632 strongly inhibited Ang II
      induced MCP-1 expression. Although inhibition of extracellular signal-regulated
      protein kinase (ERK) by PD 098,059 also inhibited Ang II-induced MCP-1
      expression, Y-27632 did not affect Ang II-induced activation of ERK. These
      results indicate that Rho-kinase plays a critical role in Ang II-induced MCP-1
      production independent of ERK. The Rho-Rho-kinase pathway may be a novel target
      for the inhibition of Ang II signaling and the treatment of atherosclerosis.

PMID- 11463769
TI  - Endothelin mediates some of the renal actions of acutely administered angiotensin
      II.
AB  - Recent studies suggest that endogenous endothelin mediates much of the
      vasoconstrictor activity and vascular fibrotic damage caused by chronic
      administration of angiotensin II. The present study uses the mixed endothelin-A
      and endothelin-B receptor antagonist bosentan and the endothelin-A-selective
      blocker BQ-123 to study the contribution of endogenous endothelin to the pressor
      and renal action of acutely administered angiotensin II in conscious, chronically
      catheterized rats. Exposure to angiotensin II at 0.48 pmol 0.5 ng/100 g body
      weight per min IV (low dose) and 1.91 pmol 2.0 ng/100 g body weight per min IV
      (high dose) raised mean arterial blood pressure (18+/-4 mm Hg, P<0.01, and 39+/-4
      mm Hg, P<0.005, respectively) while also increasing renal vascular resistance
      (4.3+/-1 mm Hg/mL per min, P<0.001, and 10+/-1 mm Hg/mL per min, P<0.001,
      respectively). In the presence of bosentan, pressor and renal vasoconstrictor
      responses to low-dose angiotensin II were blunted (P<0.02 and P<0.01,
      respectively), and the results with BQ-123 were similar. In contrast, these
      parameters were unaffected during high-dose angiotensin II infusion+bosentan,
      although BQ-123 did selectively reduce the rise in renal vascular resistance,
      possibly via an endothelin B-mediated nitric oxide effect. In contrast, high-dose
      angiotensin II caused natriuretic and diuretic effects that were completely
      prevented by bosentan. These results show that endothelin (via endothelin A)
      contributes to the pressor and renal vasoconstrictor actions of acutely
      administered low-dose angiotensin II. Furthermore, our data suggest that the
      previously described angiotensin II-induced natriuresis and diuresis observed
      with a high pressor dose of angiotensin II is mediated by endothelin.

PMID- 11463770
TI  - Angiotensinogen polymorphism M235T, carotid atherosclerosis, and small-vessel
      disease-related cerebral abnormalities.
AB  - The angiotensinogen M235T polymorphism has been linked to hypertension and
      cardiovascular disease. We studied the role of this polymorphism as a risk factor
      for carotid atherosclerosis and small-vessel disease-related brain abnormalities.
      A total of 431 randomly selected community-dwelling subjects without clinical
      evidence for strokes underwent angiotensinogen genotyping and carotid Duplex
      scanning; 1.5-T brain magnetic resonance imaging (MRI) was done in 396
      individuals. At 3-year follow-up, we reexamined 343 and 267 study participants by
      ultrasound and brain MRI, respectively. Carotid atherosclerosis was graded on a 5
      point scale. Small-vessel disease-related brain abnormalities were deep or
      subcortical white matter lesions or lacunes. Progression of carotid
      atherosclerosis and MRI findings was rated by direct imaging comparison by 3
      independent raters. The M/M, M/T, and T/T genotypes were seen in 20.9%, 52.9%,
      and 18.1% of subjects, respectively. The M235T polymorphism was neither
      associated with baseline carotid findings nor with progression of carotid
      atherosclerosis. There was a trend toward more frequent small-vessel disease
      related MRI abnormalities in the T/T than in the other genotypes at the baseline
      examination. Progression of brain lesions occurred significantly more commonly in
      T/T than in M/M and M/T carriers (P<0.001). Logistic regression analysis
      identified the T/T genotype (odds ratio, 3.19; P=0.002) and arterial hypertension
      (odds ratio, 3.06; P=0.03) as significant independent predictors of lesion
      progression. These data suggest that the angiotensinogen T/T genotype at position
      235 is a genetic marker for brain lesions from and progression of small vessel
      disease but not for extracranial carotid atherosclerosis.

PMID- 11463771
TI  - Characterization of the microglial response to cerebral ischemia in the stroke
      prone spontaneously hypertensive rat.
AB  - Stroke-prone spontaneously hypertensive rats (SHRSP) sustain more ischemic damage
      after middle cerebral artery occlusion than do their reference strain, the Wistar
      Kyoto rat (WKY). The cause of increased stroke sensitivity is still under
      investigation. In general, SHRSP display a greater response to inflammatory
      stimuli than do WKY. Because inflammatory cells may influence the extent of
      damage in experimental stroke, this study has investigated the acute inflammatory
      response to focal ischemia in SHRSP and WKY. Adult male SHRSP (n=5) and WKY (n=5)
      were anesthetized and underwent distal middle cerebral artery occlusion. After 24
      hours of recovery, infarct volume, neutrophil counts, and activated microglia
      counts were performed. SHRSP displayed more ischemic damage than did WKY (135+/
      4.7 versus 102+/-4.7 mm(3) [mean+/-SEM], P<0.005). Brain neutrophil counts were
      extremely low in both strains. SHRSP displayed significantly more activated
      microglia than did WKY in the ipsilateral hemisphere (respective SHRSP versus WKY
      values [mean+/-SEM] were 88+/-3.6 versus 51+/-3.4 per mm(2) for the cortical peri
      infarct region [P<0.005] and 183+/-7.9 versus 156+/-3.7 per mm(2) for the infarct
      core [P<0.05]) and in the contralateral hemisphere (eg, respective SHRSP versus
      WKY values were 102+/-3.2 versus 50+/-3.1 per mm(2) for the sensorimotor cortex
      [P<0.0001]). No neutrophils and very few activated microglia were found within
      the brains of naive rats. However naive SHRSP possessed more microglia (resting
      and activated) than did naive WKY. This study demonstrates a more pronounced
      microglial response to focal ischemia in SHRSP compared with WKY and provides
      evidence of a potential role for inflammatory processes in response to ischemic
      damage.

PMID- 11463772
TI  - Centrally mediated effects of bromocriptine on cardiac sympathovagal balance.
AB  - Bromocriptine, a dopamine agonist, is known to lower cardiovascular mortality in
      L-dopa-treated patients with Parkinson's disease, probably by reducing the
      cardiac sympathetic activity. We aimed at unmasking the central effects of
      bromocriptine on the heart by power spectrum analysis. Ten healthy subjects (aged
      31+/-2 years) in supine and sitting positions were evaluated after the
      administration of bromocriptine (2.5 mg) alone and after pharmacological
      peripheral D(2)-like blockade by domperidone (20 mg). We calculated
      (autoregressive method) the following: the low-frequency (LF) component (an index
      of cardiac sympathetic tone), the high-frequency (HF) component (an index of
      cardiac vagal tone), and the LF/HF ratio (an index of cardiac sympathovagal
      balance). With subjects in the supine position, bromocriptine alone induced a
      significant increase in the LF component and the LF/HF ratio, together with a
      reduction in norepinephrine plasma levels and blood pressure values. These
      conflicting effects can be explained as the combined result of direct and
      indirect (reflex-mediated) actions of bromocriptine in vivo. No changes in
      cardiac autonomic drive were observed with subjects in the sitting position.
      After domperidone pretreatment, bromocriptine induced a reduction in the LF
      component and in the LF/HF ratio. The sitting position caused an increase in
      heart rate and in the LF/HF ratio. We demonstrated both peripheral and central
      effects of bromocriptine. In particular, pretreatment with a peripheral
      antagonist (domperidone) allowed us to unmask the central effect of bromocriptine
      on cardiac sympathetic drive.

PMID- 11463773
TI  - Inhibition of baroreflex by angiotensin II via Fos expression in nucleus tractus
      solitarii of the rat.
AB  - We evaluated the modulatory action of angiotensin II at the nucleus tractus
      solitarii on spontaneous baroreceptor reflex response, the angiotensin subtype
      receptors involved, and the role of Fos protein in this process, using Sprague
      Dawley rats anesthetized with pentobarbital sodium. Microinjection bilaterally of
      angiotensin (Ang ) II (5, 10, 20, or 40 pmol) into the nucleus tractus solitarii
      significantly suppressed the spontaneous baroreceptor reflex, as represented by
      the magnitude of transfer function between systemic arterial pressure and heart
      rate signals. There also was a concomitant increase in Fos-like immunoreactivity
      in the nucleus tractus solitarii. Both the suppression of spontaneous
      baroreceptor reflex and Fos expression in nucleus tractus solitarii neurons
      elicited by Ang II were discernibly attenuated by pretreatment with or
      comicroinjection into the bilateral nucleus tractus solitarii of a 15-mer
      antisense c-fos oligonucleotide that targets against the initiation codon of c
      fos mRNA. In addition, those 2 actions of Ang II were reversed by the
      coadministration of the nonpeptide Ang II type 1 (AT(1)) receptor antagonist
      losartan (1.6 nmol) but not by the nonpeptide AT(2) receptor antagonist PD
      123,319 (1.6 nmol). Control treatments with artificial cerebrospinal fluid, sense
      cDNA, or antisense oligonucleotide with a scrambled sequence were ineffective. We
      conclude that under minimal cardiovascular perturbation, Fos expression mediated
      via activation of AT(1) subtype receptors may underlie the inhibitory modulation
      of beat-to-beat baroreflex control of blood pressure by Ang II at the nucleus
      tractus solitarii.

PMID- 11463774
TI  - Rescue of impaired angiogenesis in spontaneously hypertensive rats by
      intramuscular human tissue kallikrein gene transfer.
AB  - Angiogenesis represents a compensatory response targeted to preserve the
      integrity of tissues subjected to ischemia. The aim of the present study was to
      examine whether reparative angiogenesis is impaired in spontaneously hypertensive
      rats (SHR), as a function of progression of hypertension. In addition, the
      potential of gene therapy with human tissue kallikrein (HK) in revascularization
      was challenged in SHR and normotensive Wistar-Kyoto rats (WKY) that underwent
      excision of the left femoral artery. Expression of vascular endothelial growth
      factor and HK was upregulated in ischemic hindlimb of WKY but not of SHR.
      Capillary density was increased in ischemic adductor muscle of WKY (from 266+/-20
      to 633+/-73 capillaries/mm(2) at 28 days, P<0.001), whereas it remained unchanged
      in SHR (from 276+/-20 to 354+/-48 capillaries/mm(2), P=NS), thus compromising
      perfusion recovery as indicated by reduced plantar blood flow ratio (0.61+/-0.08
      versus 0.92+/-0.07 in WKY at 28 days, P<0.05). In separate experiments, saline or
      5x10(9) pfu adenovirus containing the HK gene (Ad.CMV-cHK) or the beta
      galactosidase gene (Ad.CMV-LacZ) was injected intramuscularly at 7 days after the
      induction of ischemia. Ad.CMV-cHK augmented capillary density and accelerated
      hemodynamic recovery in both strains, but these effects were more pronounced in
      SHR (P<0.01). Our results indicate that native angiogenic response to ischemia is
      impaired in SHR, possibly as a result of defective modulation of endothelial cell
      mitogens. Supplementation with kallikrein, one of the growth factors found to be
      deficient in SHR, restores physiological angiogenic response utilitarian for
      tissue healing. Our discoveries may have important implications in vascular
      medicine for therapeutic benefit.

PMID- 11463775
TI  - Potentiation of kinin analogues by ramiprilat is exclusively related to their
      degradation.
AB  - The potentiation of kinin actions represents a cardioprotective property of ACE
      inhibitors. Although a clear contribution to this effect is related to the
      inhibition of bradykinin (BK) breakdown, the high efficacy of potentiation and
      the ability of ACE inhibitors to provoke a B(2)-receptor-mediated response even
      after receptor desensitization has also triggered hypotheses concerning
      additional mechanisms of kinin potentiation. The application of kinin analogues
      with enhanced metabolic stability for the demonstration of degradation
      independent mechanisms of potentiation, however, has yielded inconsistent
      results. Therefore, the relation between the susceptibility of B(2)-agonists to
      ACE and the potentiation of their actions by ACE inhibitors was investigated with
      the use of minimally modified kinin derivatives that varied in their degree of
      ACE resistance. The B(2)-agonists BK, D-Arg-[Hyp(3)]-BK, [Hyp,(3) Tyr(Me)(8)]-BK,
      [DeltaPhe(5)]-BK, [D-NMF(7)]-BK, and [Phe(8)psi(CH(2)-NH)Arg(9)]-BK were tested
      for degradation by purified rabbit ACE and for their potency in contracting the
      endothelium-denuded rabbit jugular vein in the absence and presence of
      ramiprilat. Purified ACE degraded D-Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK
      at 81% and 71% of BK degradation activity, respectively, whereas other peptides
      were highly ([DeltaPhe(5)]-BK) or completely ([D-NMF(7)]-BK, [Phe(8)psi(CH(2)
      NH)Arg(9)]-BK) resistant. The EC(50) of BK-induced venoconstriction (1.15+/-0.2
      nmol/L) was reduced by a factor of 5.7 in the presence of ramiprilat. Likewise, D
      Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK were both significantly potentiated
      by a factor of 4.4, whereas the activities of the other agonists were not
      affected. Ramiprilat exerted no influence on the maximum contraction induced by
      any of the agonists. It is concluded that the potentiation of kinin analogues
      during ACE inhibition correlates quantitatively with the susceptibility of each
      substance to degradation by ACE. As such, no evidence of degradation-independent
      potentiating actions of ACE inhibitors could be obtained.

PMID- 11463776
TI  - Renal blood flow dynamics and arterial pressure lability in the conscious rat.
AB  - It is not known whether renal blood flow (RBF) is still autoregulated when the
      kidney is exposed to large transient blood pressure (BP) fluctuations such as
      those occurring spontaneously in conscious sinoaortic baroreceptor-denervated
      (SAD) rats. In this study, BP and RBF were simultaneously recorded in 8 SAD rats
      (2 weeks before study) and 8 baroreceptor-intact rats during approximately 3
      hours of spontaneous activity. The kidney used for RBF recordings was denervated
      to prevent the interference of changes in renal sympathetic tone with
      autoregulatory mechanisms. In intact rats, RBF variability (coefficient of
      variation 9.1+/-0.8%) was larger (P<0.02) than BP variability (5.9+/-0.2%). This
      was mainly because of slow changes in RBF that were unrelated to BP and also to a
      prominent oscillation of RBF of approximately 0.25-Hz frequency. Autoregulatory
      patterns were identified at frequencies <0.1 Hz and provided a modest attenuation
      of BP fluctuations. In SAD rats, RBF variability (12.4+/-1.6%) was lower (P<0.02)
      than BP variability (18.2+/-1.1%). Autoregulation powerfully attenuated BP
      changes <0.1 Hz (normalized transfer gain 0.21+/-0.02 in the 0.0015- to 0.01-Hz
      frequency range) but at the expense of an oscillation located at approximately
      0.05 Hz that possibly reflected the operation of the tubuloglomerular feedback.
      Large transient hypertensive episodes were not translated into RBF changes in SAD
      rats. We conclude that autoregulatory mechanisms have an ample capacity to
      protect the kidney against spontaneous BP fluctuations in the conscious rat. This
      capacity is not fully used under normal conditions of low BP variability.

PMID- 11463781
TI  - Expression analysis using oligonucleotide microarrays in mice lacking bradykinin
      type 2 receptors.
AB  - We recently conducted detailed cardiovascular and blood pressure-related
      phenotypic studies of mice lacking the bradykinin-B(2) receptor and were unable
      to identify a phenotype despite insensitivity to infused bradykinin. We therefore
      used oligonucleotide microarray analysis of some 12 000 genes and expressed
      sequence tags to identify molecular mechanisms that might be involved in
      compensating for the lack of a functional B(2) receptor in the kidneys of the
      mice. We identified 2 gene families that may have an impact on cardiovascular
      regulation and the bradykinin pathway. A water transport channel in the kidney,
      AQP4, was downregulated in the mice, whereas other members of the gene family did
      not show differences in expression levels. In addition, a number of serine
      proteases were upregulated in B(2) receptor-deficient mice. These genes are all
      located within a gene cluster on mouse chromosome 7. The findings were verified
      by an independent method. We suggest that microarray analysis has usefulness in
      elucidating otherwise unappreciated compensatory signaling pathways.

PMID- 11463782
TI  - Do beta-blockers put on weight?

PMID- 11463783
TI  - Herpesvirus saimiri replaces ZAP-70 for CD3- and CD2-mediated T cell activation.
AB  - The protein tyrosine kinase ZAP-70 plays a pivotal role involved in signal
      transduction through the T cell receptor and CD2. Defects in ZAP-70 result in
      severe combined immunodeficiency. We report that Herpesvirus saimiri, which does
      not code for a ZAP-70 homologue, can replace this tyrosine kinase. H. saimiri is
      an oncogenic virus that transforms human T cells to stable growth based on mutual
      CD2-mediated activation. Although CD2-mediated proliferation of ZAP-70-deficient
      uninfected T cells was absent, we could establish H. saimiri-transformed T cell
      lines from two unrelated patients presenting with ZAP-70 deficiencies. In these
      cell lines, CD2 and CD3 activation were restored in terms of [Ca(2+)](i), MAPK
      activation, cytokine production, and proliferation. Activation-induced tyrosine
      phosphorylation of zeta remained defective. The transformed cells expressed very
      high levels of the ZAP-70-related kinase Syk. This increased expression was not
      observed in the primary T cells from the patients and was not due to the
      transformation by the virus because transformed cell lines established from
      control T cells did not present this particularity. In conclusion, wild type H.
      saimiri can restore CD2- and CD3-mediated activation in signaling-deficient human
      T cells. It extends our understanding of interactions between the oncogenic H.
      saimiri and the infected host cells.

PMID- 11463784
TI  - Assembly of DNA polymerase III holoenzyme: co-assembly of gamma and tau is
      inhibited by DnaX complex accessory proteins but stimulated by DNA polymerase III
      core.
AB  - Although the two alternative Escherichia coli dnaX gene products, tau and gamma,
      are found co-assembled in purified DNA polymerase III holoenzyme, the pathway of
      assembly is not well understood. When the 10 subunits of holoenzyme are
      simultaneously mixed, they rapidly form a nine-subunit assembly containing tau
      but not gamma. We developed a new assay based on the binding of complexes
      containing biotin-tagged tau to streptavidin-coated agarose beads to investigate
      the effects of various DNA polymerase III holoenzyme subunits on the kinetics of
      co-assembly of gamma and tau into the same complex. Auxiliary proteins in
      combination with delta' almost completely blocked co-assembly, whereas chipsi or
      delta' alone slowed the association only moderately compared with the interaction
      of tau with gamma alone. In contrast, DNA polymerase III core, in the absence of
      deltadelta' and chipsi, accelerated the co-assembly of tau and gamma, suggesting
      a role for DNA polymerase III' [tau(2)(pol III core)(2)] in the assembly pathway
      of holoenzyme.

PMID- 11463785
TI  - Characterization of Escherichia coli MoeB and its involvement in the activation
      of molybdopterin synthase for the biosynthesis of the molybdenum cofactor.
AB  - Amino acid sequence comparisons of Escherichia coli MoeB suggested that the MoeB
      dependent formation of a C-terminal thiocarboxylate on the MoaD subunit of
      molybdopterin synthase might resemble the ubiquitin-activating step in the
      ubiquitin-targeted degradation of proteins in eukaryotes. To determine the exact
      role of MoeB in molybdopterin biosynthesis, the protein was purified after
      homologous overexpression. Using purified proteins, we have demonstrated the ATP
      dependent formation of a complex of MoeB and MoaD adenylate that is stable to gel
      filtration. Mass spectrometry of the complex revealed a peak of a molecular mass
      of 9,073 Da, the expected mass of MoaD adenylate. However, unlike the ubiquitin
      activation reaction, the formation of a thioester intermediate between MoeB and
      MoaD could not be observed. There was also no evidence for a MoeB-bound sulfur
      during the sulfuration of MoaD. Amino acid substitutions were generated in every
      cysteine residue in MoeB. All of these exhibited activity comparable to the wild
      type, with the exception of mutations in cysteine residues located in putative Zn
      binding motifs. For these cysteines, loss of activity correlated with loss of
      metal binding.

PMID- 11463786
TI  - The cleavage of Akt/protein kinase B by death receptor signaling is an important
      event in detachment-induced apoptosis.
AB  - Epithelial cells undergo death receptor-dependent apoptosis when detached from
      matrix, a process termed anoikis. Activation of Akt/protein kinase B (PKB) by
      matrix attachment protects cells from anoikis. In this study, we establish a link
      between anoikis and Akt/PKB-mediated survival by demonstrating that Akt/PKB is
      cleaved by caspases in matrix-detached epithelial cells by a mechanism that
      involves death receptors. Reduced levels of Akt/PKB protein were observed in
      detached Madin-Darby canine kidney cells relative to cells attached to collagen.
      Equivalent levels of Akt/PKB, however, were detected in matrix-adherent and
      detached cells after inhibition of caspase activity or expression of an Akt/PKB
      mutant (D108+119A) that is resistant to caspase cleavage. The contribution of
      death domain-containing proteins to Akt/PKB cleavage was evidenced by the ability
      of dominant negative Fas-associated death domain to restore normal levels of
      Akt/PKB in matrix-detached cells. Importantly, expression of a cleavage-resistant
      Akt/PKB mutant protected matrix-detached cells from apoptosis. These studies
      suggest that members of the death receptor family promote the caspase-mediated
      cleavage of Akt/PKB and that this event contributes to anoikis.

PMID- 11463787
TI  - tau binds and organizes Escherichia coli replication proteins through distinct
      domains: domain III, shared by gamma and tau, oligomerizes DnaX.
AB  - The tau and gamma proteins of the DNA polymerase III holoenzyme DnaX complex are
      products of the dnaX gene with gamma being a truncated version of tau arising
      from ribosomal frameshifting. tau is comprised of five structural domains, the
      first three of which are shared by gamma (Gao, D., and McHenry, C. (2001) J.
      Biol. Chem. 276, 4433-4453). In the absence of the other holoenzyme subunits,
      DnaX exists as a tetramer. Association of delta, delta', chi, and psi with domain
      III of DnaX(4) results in a DnaX complex with a stoichiometry of
      DnaX(3)deltadelta'chipsi. To identify which domain facilitates DnaX self
      association, we examined the properties of purified biotin-tagged DnaX fusion
      proteins containing domains I-II or III-V. Unlike domain I-II, treatment of
      domain III-V, gamma, and tau with the chemical cross-linking reagent BS3 resulted
      in the appearance of high molecular weight intramolecular cross-linked protein.
      Gel filtration of domains I-II and III-V demonstrated that domain I-II was
      monomeric, and domain III-V was an oligomer. Biotin-tagged domain III-V, and not
      domain I-II, was able to form a mixed DnaX complex by recruiting tau, delta,
      delta', chi, and psi onto streptavidin-agarose beads. Thus, domain III not only
      contains the delta, delta', chi, and psi binding interface, but also the region
      that enables DnaX to oligomerize.

PMID- 11463788
TI  - From brain to bile. Evidence that conjugation and omega-hydroxylation are
      important for elimination of 24S-hydroxycholesterol (cerebrosterol) in humans.
AB  - The brain is the almost exclusive site of formation of 24S-hydroxycholesterol in
      man, and there is a continuous flux of this oxysterol across the blood-brain
      barrier into the circulation. The hepatic metabolism of 24S-hydroxycholesterol
      was studied here by three different approaches: incubation of tritium-labeled 24S
      hydroxycholesterol with human primary hepatocytes, administration of tritium
      labeled 24S-hydroxycholesterol to a human volunteer, and quantitation of free and
      conjugated 24S-hydroxycholesterol and its neutral metabolites in ileocecal fluid
      from patients with ileal fistulae. 24S-Hydroxycholesterol as well as 24R
      hydroxycholesterol were converted into bile acids by human hepatocytes at a rate
      of about 40% of that of the normal intermediate in bile acid synthesis, 7 alpha
      hydroxycholesterol. There was also a conversion of 24S-hydroxycholesterol into
      conjugate(s) of 5-cholestene-3 beta,24S,27-triol at a rate similar to the that of
      conversion into bile acids. When administered to a human volunteer, labeled 24S
      hydroxycholesterol was converted into bile acids at about half the rate of
      simultaneously administered labeled 7 alpha-hydroxycholesterol. Free, sulfated,
      and glucuronidated 24S-hydroxycholesterol and 5-cholestene-3 beta,24,27-triol
      were identified in ileocecal fluid. The excretion of these steroids was about 3.5
      mg/24 h, amounting to more than 50% of the total estimated flux of 24S
      hydroxycholesterol from the brain. It is concluded that 24S-hydroxycholesterol is
      a less efficient precursor to bile acids and that about half of it is conjugated
      and eliminated in bile as such or as a conjugate of a 27-hydroxylated metabolite.
      The less efficient metabolism of 24S-hydroxycholesterol may explain the
      surprisingly high levels of this oxysterol in the circulation and is of interest
      in relation to the suggested role of 24S-hydroxycholesterol as a regulator of
      cholesterol homeostasis.

PMID- 11463789
TI  - Fusion of human neutrophil phagosomes with lysosomes in vitro: involvement of
      tyrosine kinases of the Src family and inhibition by mycobacteria.
AB  - The intracellular killing of microorganisms in phagocytes involves the fusion of
      lysosomes containing bactericidal factors with phagosomes, and several
      intracellular pathogens are able to inhibit this fusion event. In this study, we
      report the reconstitution of phagosome-lysosome fusion in vitro, using an assay
      based on resonance energy transfer between fluorescent phospholipid analogues
      that were inserted into whole human NB4-neutrophil membranes from liposomes
      containing positively charged lipids. Cytosol was required for fusion, and fusion
      was stimulated 3-fold if this cytosol had been prepared from neutrophils
      activated by using opsonized zymosan or a combination of the calcium ionophore
      (A23187) and phorbol myristate acetate (PMA). Fusion was inhibited by the
      addition of PP1, an inhibitor of Src family protein kinases, or GTPgammaS. We
      have previously reported that the biogenesis of phagolysosomes in human
      neutrophils is inhibited by mycobacteria. Here we show that cytosol from cells
      having internalized live (not heat-killed) Mycobacterium smegmatis or cytosol
      simply incubated with mycobacteria inhibited fusion, indicating that soluble
      factors are involved in mycobacterial inhibition of phagosome-lysosome fusion.

PMID- 11463790
TI  - Molecular basis for selectivity of high affinity peptide antagonists for the
      gastrin-releasing peptide receptor.
AB  - Few gastrointestinal hormones/neurotransmitters have high affinity peptide
      receptor antagonists, and little is known about the molecular basis of their
      selectivity or affinity. The receptor mediating the action of the mammalian
      bombesin (Bn) peptide, gastrin-releasing peptide receptor (GRPR), is an
      exception, because numerous classes of peptide antagonists are described. To
      investigate the molecular basis for their high affinity for the GRPR, two classes
      of peptide antagonists, a statine analogue, JMV594 ([d-Phe(6),Stat(13)]Bn(6-14)),
      and a pseudopeptide analogue, JMV641 (d-Phe-Gln-Trp-Ala-Val-Gly-His-Leupsi(CHOH
      CH(2))-(CH(2))(2)-CH(3)), were studied. Each had high affinity for the GRPR and
      >3,000-fold selectivity for GRPR over the closely related neuromedin B receptor
      (NMBR). To investigate the basis for this, we used a chimeric receptor approach
      to make both GRPR loss of affinity and NMBR gain of affinity chimeras and a site
      directed mutagenesis approach. Chimeric or mutated receptors were transiently
      expressed in Balb/c 3T3. Only substitution of the fourth extracellular (EC)
      domain of the GRPR by the comparable NMBR domain markedly decreased the affinity
      for both antagonists. Substituting the fourth EC domain of NMBR into the GRPR
      resulted in a 300-fold gain in affinity for JMV594 and an 11-fold gain for
      JMV641. Each of the 11 amino acid differences between the GRPR and NMBR in this
      domain were exchanged. The substitutions of Thr(297) in GRPR by Pro from the
      comparable position in NMBR, Phe(302) by Met, and Ser(305) by Thr decreased the
      affinity of each antagonist. Simultaneous replacement of Thr(297), Phe(302), and
      Ser(305) in GRPR by the three comparable NMBR amino acids caused a 500-fold
      decrease in affinity for both antagonists. Replacing the comparable three amino
      acids in NMBR by those from GRPR caused a gain in affinity for each antagonist.
      Receptor modeling showed that each of these three amino acids faced inward and
      was within 5 A of the putative binding pocket. These results demonstrate that
      differences in the fourth EC domain of the mammalian Bn receptors are responsible
      for the selectivity of these two peptide antagonists. They demonstrate that
      Thr(297), Phe(302), and Ser(305) of the fourth EC domain of GRPR are the critical
      residues for determining GRPR selectivity and suggest that both receptor-ligand
      cation-pi interactions and hydrogen bonding are important for their high affinity
      interaction.

PMID- 11463791
TI  - The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated
      genes.
AB  - To gain insight into the molecular mechanisms underlying cutaneous wound repair,
      we performed a large scale screen to identify novel injury-regulated genes. Here
      we show a strong up-regulation of the RNA and protein levels of the two Ca(2+)
      binding proteins S100A8 and S100A9 in the hyperthickened epidermis of acute
      murine and human wounds and of human ulcers. Furthermore, both genes were
      expressed by inflammatory cells in the wound. The increased expression of S100A8
      and S100A9 in wound keratinocytes is most likely related to the activated state
      of the keratinocytes and not secondary to the inflammation of the skin, since we
      also found up-regulation of S100A8 and S100A9 in the epidermis of activin
      overexpressing mice, which develop a hyperproliferative and abnormally
      differentiated epidermis in the absence of inflammation. Furthermore, S100A8 and
      S100A9 expression was found to be associated with partially differentiated
      keratinocytes in vitro. Using confocal microscopy, both proteins were shown to be
      at least partially associated with the keratin cytoskeleton. In addition,
      cultured keratinocytes efficiently secreted the S100A8/A9 dimer. These results
      together with previously published data suggest that S100A8 and S100A9 are novel
      players in wound repair, where they might be involved in the reorganization of
      the keratin cytoskeleton in the wounded epidermis, in the chemoattraction of
      inflammatory cells, and/or in the defense against microorganisms.

PMID- 11463792
TI  - Modulation of glucose-6-phosphate dehydrogenase activity and expression is
      associated with aryl hydrocarbon resistance in vitro.
AB  - The mutagenic effect of environmental carcinogens has been well documented in
      animal models and in human studies but the mechanisms involved in preventing
      carcinogen insult have not been fully elucidated. In this study we examined the
      molecular and biochemical changes associated with carcinogen resistance in a
      series of aryl hydrocarbon-resistant MCF-7 cell lines developed by exposure to
      benzo[a]pyrene (BP). The cell lines were designated as AH(R40), AH(R100), and
      AH(R200) to denote their increasing fold resistance to BP compared with wild type
      cells. These cell lines were also resistant to another aryl hydrocarbon (AH),
      dimethylbenz[a]anthracene, but not to pleiotropic drugs (doxorubicin,
      vinblastine, and taxol). The resistant cell lines showed an increase in the level
      of the primary intracellular antioxidant, reduced glutathione, corresponding to
      increasing AH resistance. However, there was no change in glutathione reductase
      activity. The generation of reduced glutathione requires NADPH, and we therefore
      examined the activity and expression of the rate-limiting enzyme in NADPH
      production, glucose-6-phosphate dehydrogenase (G6PD). An increase in G6PD
      specific activity was associated with increasing aryl hydrocarbon resistance.
      This was due to an increased expression of G6PD in resistant cells, which was
      demonstrated by increases in both protein and mRNA levels. However, there was no
      increase in the transcription rate of G6PD in the resistant cell lines,
      indicating that the increase G6PD expression is due to a post-transcriptional
      modulation, which was confirmed by actinomycin D chase experiments. These results
      demonstrate that modulation of G6PD expression and activity is an important
      mechanism in AH resistance.

PMID- 11463793
TI  - An essential function of Saccharomyces cerevisiae RNA triphosphatase Cet1 is to
      stabilize RNA guanylyltransferase Ceg1 against thermal inactivation.
AB  - Saccharomyces cerevisiae RNA triphosphatase (Cet1) and RNA guanylyltransferase
      (Ceg1) interact in vivo and in vitro to form a bifunctional mRNA capping enzyme
      complex. Here we show that the guanylyltransferase activity of Ceg1 is highly
      thermolabile in vitro (98% loss of activity after treatment for 10 min at 35
      degrees C) and that binding to recombinant Cet1 protein, or a synthetic peptide
      Cet1(232-265), protects Ceg1 from heat inactivation at physiological
      temperatures. Candida albicans guanylyltransferase Cgt1 is also thermolabile and
      is stabilized by binding to Cet1(232-265). In contrast, Schizosaccharomyces pombe
      and mammalian guanylyltransferases are intrinsically thermostable in vitro and
      they are unaffected by Cet1(232-265). We show that the requirement for the Ceg1
      binding domain of Cet1 for yeast cell growth can be circumvented by
      overexpression in high gene dosage of a catalytically active mutant lacking the
      Ceg1-binding site (Cet1(269-549)) provided that Ceg1 is also overexpressed.
      However, such cells are unable to grow at 37 degrees C. In contrast, cells
      overexpressing Cet1(269-549) in single copy grow at all temperatures if they
      express either the S. pombe or mammalian guanylyltransferase in lieu of Ceg1.
      Thus, the cell growth phenotype correlates with the inherent thermal stability of
      the guanylyltransferase. We propose that an essential function of the Cet1-Ceg1
      interaction is to stabilize Ceg1 guanylyltransferase activity rather than to
      allosterically regulate its activity. We used protein-affinity chromatography to
      identify the COOH-terminal segment of Ceg1 (from amino acids 245-459) as an
      autonomous Cet1-binding domain. Genetic experiments implicate two peptide
      segments, (287)KPVSLYVW(295) and (337)WQNLKNLEQPLN(348), as likely constituents
      of the Cet1-binding site on Ceg1.

PMID- 11463794
TI  - Altered regulation of ERK1b by MEK1 and PTP-SL and modified Elk1 phosphorylation
      by ERK1b are caused by abrogation of the regulatory C-terminal sequence of ERKs.
AB  - ERK1b is an alternatively spliced form of ERK1, containing a 26-amino acid
      insertion between residues 340 and 341 of ERK1. Although under most circumstances
      the kinetics of ERK1b activation are similar to that of ERK1 and ERK2, we have
      previously found several conditions under which the activation of ERK1b by
      extracellular stimuli differs from that of other ERKs. We studied the molecular
      mechanisms that cause this differential regulation of ERK1b and found that ERK1b
      is altered in its ability to interact with MEK1 and this influenced its
      subcellular localization but not its kinetics of activation. ERK1b had a
      decreased ability to phosphorylate Elk1, but this did not change much the
      transcriptional activity of the latter. Importantly, the interaction of ERK1b
      with PTP-SL, which can act as a MAPK phosphatase, shortly after mitogenic
      stimulation, was significantly affected as well. Using mutants of ERK1b we found
      that the differential interaction of ERK1b with the three effectors is caused by
      the site of insertion that abrogates the cytosolic retention sequence/common
      docking motif of ERKs, and is not dependent on the actual sequence of the insert.
      Prolonged epidermal growth factor stimulation of Rat1 cells resulted in a
      differential inactivation and not activation of ERK1b as compared with ERK1 and
      ERK2. The reduced sensitivity to phosphatases without major differences in the
      kinetics of activation or activation of substrates, suggests that ERK1b plays a
      role in the transmission of extracellular signals under conditions of persistent
      stimulation, where ERK1b and MAPK phosphatases are induced, and the activity of
      ERK1 and ERK2 is suppressed.

PMID- 11463795
TI  - Glucose activates protein kinase C-zeta /lambda through proline-rich tyrosine
      kinase-2, extracellular signal-regulated kinase, and phospholipase D: a novel
      mechanism for activating glucose transporter translocation.
AB  - Insulin controls glucose uptake by translocating GLUT4 and other glucose
      transporters to the plasma membrane in muscle and adipose tissues by a mechanism
      that appears to require protein kinase C (PKC)-zeta/lambda operating downstream
      of phosphatidylinositol 3-kinase. In diabetes mellitus, insulin-stimulated
      glucose uptake is diminished, but with hyperglycemia, uptake is maintained but by
      uncertain mechanisms. Presently, we found that glucose acutely activated PKC
      zeta/lambda in rat adipocytes and rat skeletal muscle preparations by a mechanism
      that was independent of phosphatidylinositol 3-kinase but, interestingly,
      dependent on the apparently sequential activation of the dantrolene-sensitive,
      nonreceptor proline-rich tyrosine kinase-2; components of the extracellular
      signal-regulated kinase (ERK) pathway, including, GRB2, SOS, RAS, RAF, MEK1 and
      ERK1/2; and, most interestingly, phospholipase D, thus yielding increases in
      phosphatidic acid, a known activator of PKC-zeta/lambda. This activation of PKC
      zeta/lambda, moreover, appeared to be required for glucose-induced increases in
      GLUT4 translocation and glucose transport in adipocytes and muscle cells. Our
      findings suggest the operation of a novel pathway for activating PKC-zeta/lambda
      and glucose transport.

PMID- 11463796
TI  - Purification and characterization of an acid amidase selective for N
      palmitoylethanolamine, a putative endogenous anti-inflammatory substance.
AB  - N-Arachidonoylethanolamine (anandamide) is cannabimimetic, and N
      palmitoylethanolamine is anti-inflammatory and immunosuppressive. We found an
      amidase that is more active with the latter than the former in contrast to the
      previously known anandamide amidohydrolase for which N-palmitoylethanolamine is a
      poor substrate. Proteins solubilized by freezing and thawing from the 12,000 x g
      pellet of various rat organs hydrolyzed [(14)C]N-palmitoylethanolamine to
      palmitic acid and ethanolamine. The specific enzyme activity was higher in the
      order of lung > spleen > small intestine > thymus > cecum, and high activity was
      found in peritoneal and alveolar macrophages. The enzyme with a molecular mass of
      31 kDa was purified from rat lung to a specific activity of 1.8 micromol/min/mg
      protein. Relative reactivities of the enzyme with various N-acylethanolamines
      (100 microm) were as follows: N-palmitoylethanolamine, 100%; N
      myristoylethanolamine, 48%; N-stearoylethanolamine, 21%; N-oleoylethanolamine,
      20%; N-linoleoylethanolamine, 13%; anandamide, 8%. The enzyme was the most active
      at pH 5 and was activated 7-fold by Triton X-100. The enzyme was almost
      insensitive to methyl arachidonyl fluorophosphonate, which inhibited anandamide
      amidohydrolase potently. Thus, the new enzyme referred to as N
      palmitoylethanolamine hydrolase was clearly distinguishable from anandamide
      amidohydrolase.

PMID- 11463797
TI  - MIST functions through distinct domains in immunoreceptor signaling in the
      presence and absence of LAT.
AB  - MIST (also termed Clnk) is an adaptor protein structurally related to SLP-76 and
      BLNK/BASH/SLP-65 hematopoietic cell-specific adaptor proteins. By using the BLNK
      deficient DT40 chicken B cell system, we demonstrated MIST functions through
      distinct intramolecular domains in immunoreceptor signaling depending on the
      availability of linker for activation of T cells (LAT). MIST can partially
      restore the B cell antigen receptor (BCR) signaling in the BLNK-deficient cells,
      which requires phosphorylation of the two N-terminal tyrosine residues. Co
      expression of LAT with MIST fully restored the BCR signaling and dispenses with
      the requirement of the two tyrosines in MIST for BCR signaling. However, some
      other tyrosine(s), as well as the Src homology (SH) 2 domain and the two proline
      rich regions in MIST, is still required for full reconstitution of the BCR
      signaling, in cooperation with LAT. The C-terminal proline-rich region of MIST is
      dispensable for the LAT-aided full restoration of MAP kinase activation, although
      it is responsible for the interaction with LAT and for the localization in
      glycolipid-enriched microdomains. On the other hand, the N-terminal proline-rich
      region, which is a binding site of the SH3 domain of phospholipase Cgamma, is
      essential for BCR signaling. These results revealed a marked plasticity of MIST
      function as an adaptor in the cell contexts with or without LAT.

PMID- 11463798
TI  - Enhanced sensitivity of insulin-resistant adipocytes to vanadate is associated
      with oxidative stress and decreased reduction of vanadate (+5) to vanadyl (+4).
AB  - Vanadate (sodium orthovanadate), an inhibitor of phosphotyrosine phosphatases
      (PTPs), mimics many of the metabolic actions of insulin in vitro and in vivo. The
      potential of vanadate to stimulate glucose transport independent of the early
      steps in insulin signaling prompted us to test its effectiveness in an in vitro
      model of insulin resistance. In primary rat adipocytes cultured for 18 h in the
      presence of high glucose (15 mm) and insulin (10(-7) m), sensitivity to insulin
      stimulated glucose transport was decreased. In contrast, there was a paradoxical
      enhanced sensitivity to vanadate of the insulin-resistant cells (EC(50) for
      control, 325 +/- 7.5 microm; EC(50) for insulin-resistant, 171 +/- 32 microm; p <
      0.002). Enhanced sensitivity was also present for vanadate stimulation of insulin
      receptor kinase activity and autophosphorylation and Akt/protein kinase B Ser-473
      phosphorylation consistent with more effective PTP inhibition in the resistant
      cells. Investigation of this phenomenon revealed that 1) depletion of GSH with
      buthionine sulfoximine reproduced the enhanced sensitivity to vanadate while
      preincubation of resistant cells with N-acetylcysteine (NAC) prevented it, 2)
      intracellular GSH was decreased in resistant cells and normalized by NAC, 3)
      exposure to high glucose and insulin induced an increase in reactive oxygen
      species, which was prevented by NAC, 4) EPR (electron paramagnetic resonance)
      spectroscopy showed a decreased amount of vanadyl (+4) in resistant and
      buthionine sulfoximine-treated cells, which correlated with decreased GSH and
      increased vanadate sensitivity, while total vanadium uptake was not altered, and
      5) inhibition of recombinant PTP1B in vitro was more sensitive to vanadate (+5)
      than vanadyl (+4). In conclusion, the paradoxical increased sensitivity to
      vanadate in hyperglycemia-induced insulin resistant adipocytes is due to
      oxidative stress and decreased reduction of vanadate (+5) to vanadyl (+4). Thus,
      sensitivity of PTP inhibition and glucose transport to vanadate is regulated by
      cellular redox state.

PMID- 11463799
TI  - Perioperative high dose rate brachytherapy for soft tissue sarcoma.

PMID- 11463800
TI  - Supratentorial astrocytomas and oligodendrogliomas treated in the MRI era.
AB  - BACKGROUND: There is at present no consensus on the policy for the treatment of
      patients with low-grade gliomas (LGGs). METHODS: This report is a retrospective
      multi-institutional study of 100 patients (ages 16-65 years) with astrocytoma
      (grade II), oligodendroglioma, anaplastic oligodendroglioma and anaplastic
      oligoastrocytoma of the supratentorial areas which were treated with surgery and
      postoperative radiotherapy at five university hospitals in northern Japan between
      1990 and 1997 when MRI was routinely used to determine the target volume. Most
      patients were irradiated with 50-60 Gy. The target volume usually covered the
      areas with T2 prolongation of MRI with a margin of 2 cm. RESULTS: The disease
      specific 5-year survival rate was 87.4% for patients with oligodendroglioma and
      75.3% for patients with astrocytoma. Survival for patients with astrocytoma in
      the MRI era appears to be improved compared with historical controls in the
      literature. Patients with astrocytoma aged 40 years and under had a significantly
      better disease-specific survival rate than those over 40 years (P < 0.05) and
      patients with oligodendroglioma and oligoastrocytoma showed a similar tendency.
      Patients with astrocytoma who had over 50% of their tumor removed had a
      significantly better survival rate than those who had less than 50% removed (P <
      0.05). Chemotherapy appeared to improve the disease-specific survival rate of
      patients with oligodendroglioma but not that of patients with astrocytoma.
      CONCLUSION: Oligodendroglioma has a more protracted course of disease progression
      than astrocytoma. This particular feature and the sensitivity of LGGs to
      chemotherapy as well as their relevant prognostic factors, such as age,
      histopathology and amount of tumor removal, should be taken into account before
      any decision on treatment methods for LGGs is made.

PMID- 11463801
TI  - Radiotherapy combined with nimustine hydrochloride and etoposide for malignant
      gliomas: results of a pilot study.
AB  - BACKGROUND: The aim of this study was to examine the effectiveness of radio
      chemotherapy using nimustine hydrochloride (ACNU) and etoposide (VP-16) for
      malignant gliomas. METHODS: From 1985 through 1998, 33 consecutive patients with
      supratentorial malignant gliomas were treated by a single protocol. The mean age
      was 45.8 years (range 12-76 years). The median Karnofsky performance score was 80
      (range 60-100). There were 14 anaplastic astrocytomas (AA) and 19 glioblastomas
      (GBM). Following surgery, 60 Gy of radiotherapy combined with an adjuvant
      chemotherapy using ACNU (80 mg/m(2) i.v. days 1 and 36) and etoposide (80 mg/m(2)
      i.v. days 2, 3, 37 and 38) was administered. On completion of the initial radio
      chemotherapy, a single cycle of the same chemotherapy was repeated every 6-8
      weeks until tumor progression or for 2 years at the maximum. RESULTS: All 33
      patients tolerated treatment. We observed complete response in five cases (15%),
      partial response in nine (27%), no change in 11 (33%) and progressive disease in
      eight (24%). The response rate (>50% reduction) was therefore 42.4%. Median
      progression-free survival (PFS) for all 33 patients was 8.4 months: 7.8 months
      for GBMs and 13.5 months for AAs. There was no significant difference in PFS
      between GBM and AA patients (p = 0.14). The median survival time of all 33
      patients was 21.1 months: 16.2 months for GBMs and 49.9 months for AAs. The
      difference in survival between AA and GBM was statistically significant (p =
      0.0019). Myelosuppression appeared in 11 patients: grade 2 hematological toxicity
      in 10 cases (30%) and grade 3 in one case (3%). We did not observe any
      gastrointestinal toxicity. Multivariate analysis showed that age and initial
      histological grade had independent prognostic significance. CONCLUSION: RT with
      ACNU and etoposide are feasible and well tolerated and the treatment results were
      comparable to the best results reported in the literature.

PMID- 11463802
TI  - Intracavitary chemotherapy with 5-fluoro-2'-deoxyuridine (FdUrd) in malignant
      brain tumors.
AB  - BACKGROUND: After completing basic research on the anti-tumor effects and
      neurotoxicity of 5-fluoro-2'-deoxyuridine (FdUrd) and the balance of thymidine
      kinase and thymidine phosphorylase activities and confirming the safety of
      intrathecal FdUrd administration in a previous clinical study of meningeal
      carcinomatosis, intracavitary administration of FdUrd was performed as a second
      trial in patients with malignant glioma and metastatic brain tumors. METHODS: The
      study population consisted of 13 patients, six with glioblastoma, one with
      anaplastic astrocytoma and six with metastatic brain tumors. This treatment was
      applied for cystic, small-volume residual or recurrent tumors. FdUrd (1-10
      microg) was administered every day at least 25 times through an Ommaya device
      placed in the cyst or closed postoperative cavity reconstructed with a patch of
      galea aponeurotica. Intracavitary chemotherapy with FdUrd was preceded by
      radiation therapy in two patients but no other adjuvant therapy was performed.
      RESULTS: No side effects such as headache, nuchal pain, convulsive attack, bone
      marrow suppression or liver dysfunction were observed during the course of
      chemotherapy. Seven of the 13 patients showed responses: complete response six,
      minor response one, no change two and progressive disease four after the twenty
      fifth intracavitary administration of FdUrd when tumor sizes on CT scans and MRI
      before and after intracavitary chemotherapy were compared. CONCLUSIONS:
      Intracavitary FdUrd chemotherapy may be useful for the treatment of small-volume
      tumors.

PMID- 11463803
TI  - Validation and problems of St-Gallen recommendations of adjuvant therapy for node
      negative invasive breast cancer in Japanese patients.
AB  - BACKGROUND: The objectives of this study were to confirm the favorable outcome of
      invasive breast cancer in Japanese patients without lymph node metastasis who did
      not receive adjuvant therapies and to validate the St-Gallen recommendations in
      this population. METHODS: The subjects were a consecutive series of 920 node
      negative invasive breast cancer patients who underwent surgery between 1987 and
      1994 at our hospital. These patients did not receive adjuvant chemotherapy. Ten
      year disease-free (DFS) and overall survival (OS) rates were analyzed by the St
      Gallen risk categories (Minimal/Low, Intermediate, High). RESULTS: The median age
      of the patients at surgery was 52 years and the median follow-up period of
      patients was 10.2 years. At 10 years, the respective DFS and OS rates of all
      patients were 84.6 and 86.7%. The DFS and OS of patients in the Minimal/Low risk
      category (25 patients) both showed 100%. The DFS and OS of patients in the
      Intermediate risk category (356 patients) showed 92.0 and 93.1%, respectively.
      The DFS and OS of patients in the High risk category (539 patients) showed 79.4
      and 82.2%, respectively, indicating a significant difference between those in the
      Minimal/Intermediate risk category (381 patients) (p < 0.001, p < 0.001,
      respectively). The DFS and OS of patients who had one pathological lymph node
      metastasis (775 patients) showed 72.7 and 75.2%, respectively, which indicated a
      non-significant difference between those in the High risk category (381 patients)
      (p = 0.10). These data support the validation of adjuvant therapy for high-risk
      node-negative breast cancers in Japanese patients. However, quality control is
      needed to define the histological grade included in the risk categories.
      CONCLUSION: Japanese patients with invasive breast cancer without lymph node
      metastasis showed a survival advantage compared with their Caucasian
      counterparts. However, patients in the High risk group as defined by St-Gallen
      recommendations should be indicated for adjuvant therapy.

PMID- 11463804
TI  - What do breast cancer patients benefit from staging bone scintigraphy?
AB  - BACKGROUND: A review and analysis of breast cancer treatment records were
      conducted to establish criteria for performing disease staging by bone
      scintigraphy in Japanese breast cancer patients. METHODS: Records from 5538
      consecutive Japanese breast cancer patients from January 1988 to December 1998
      were reviewed and analyzed to determine bone metastasis status at the time of
      initial treatment. Correlation between metastasis to bone and factors known
      before and after surgery was analyzed using logistic regression. RESULTS: The
      overall incidence of metastasis to bone was 2.13% [95% confidence interval (CI):
      1.77-2.55%, 118/5538]. Multivariate logistic analysis revealed that tumor size,
      nodal involvement and histopathology correlated with metastasis to bone. Patients
      with tumors larger than 30 mm had a significantly higher probability of
      metastasis to bone, as did patients with lymph node evaluation results N > or =
      1. The incidence of metastasis to bone was 0% in patients with stage 0 disease,
      0.08% in stage I patients, 1.09% in stage II patients, 9.96% in stage III
      patients and 34.04% in stage IV patients. Stage II patients were sub-classified
      by tumor size T (small, 21-30 mm; and large, 31-50 mm), nodal involvement N and
      histopathology. The incidence of metastasis to bone in stage II patients was
      higher in patients with large tumors, scirrhous carcinoma or invasive lobular
      carcinoma or both. CONCLUSION: Bone metastasis correlated with tumor size (T),
      lymph node involvement (N) and histopathology. Using the criteria that bone
      scintigraphy is not necessary in populations with a < 1% incidence of bone
      metastasis, but is recommended at incidence > 3%, the following conclusions were
      drawn. Staging by bone scintigraphy provided no benefit to patients whose disease
      was stage I or less, stage II with small tumors or stage II with large tumors
      marked by low-grade histopathology (papillotubular cancer). Bone scintigraphy is
      recommended in patients whose disease is stage II with large tumors marked by
      high-grade histopathology (scirrhous or invasive lobular cancer), stage III or
      stage IV. Consequently, staging by bone scintigraphy could be avoided in 71%
      (3943/5538) of Japanese breast cancer patients.

PMID- 11463805
TI  - Self-expandable metallic stents for patients with recurrent esophageal carcinoma
      after failure of primary chemoradiotherapy.
AB  - BACKGROUND: Recent advances in chemoradiotherapy for esophageal carcinoma have
      resulted in improved survival rates. However, there are few options for recurrent
      dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy.
      The aim of this study was to evaluate the safety and efficacy of self-expandable
      metallic stent placement for patients with recurrent esophageal carcinoma where
      definitive chemoradiotherapy has failed. METHODS: Thirteen consecutive patients
      with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable
      metallic stents were placed after failure of primary chemoradiotherapy, were
      studied retrospectively. All patients had esophageal obstruction or malignant
      fistula. RESULTS: The oral alimentation status of nine of 13 patients (69%)
      improved after successful placement of the stent. Following placement of the
      stent, fever (>38 degrees C) and severe chest pain occurred in 85% (11/13) of the
      patients. In all patients examined, C-reactive protein was elevated within 1 week
      of the operation. Esophageal perforation occurred in three patients. Stent
      related mediastinitis and pneumonia developed in six (46%) and three (23%)
      patients, respectively. Seven of the 13 patients (54%) died of stent-related
      pulmonary complications. CONCLUSION: Although the placement of a self-expandable
      metallic stent for patients with recurrent esophageal carcinoma after failure of
      chemoradiotherapy improved their oral alimentation status, we found that this
      treatment increases the risk of life-threatening pulmonary complications.

PMID- 11463806
TI  - Phase II trial of outpatient schedule of paclitaxel in patients with previously
      untreated metastatic, measurable adenocarcinoma of the stomach.
AB  - BACKGROUND: Chemotherapy represents the standard treatment for patients with
      metastatic stomach cancer. Conflicting results have been published regarding the
      activity of paclitaxel in this setting. Therefore, we developed a phase II study
      to evaluate an outpatient 3 h infusion of paclitaxel. METHODS: Patients with
      chemonaive metastatic stomach cancer received paclitaxel 210 mg/m(2) every 3
      weeks. Patients with esophageal cancer were not eligible. RESULTS: Twenty-one
      patients were enrolled. The median age was 55.5 years (range 37-81 years). Two
      partial responses were observed among the 18 patients evaluable for response and
      toxicity (response rate 11%, 95% CI: 2-33%). The median time to progression was
      10.5 weeks and median survival 23 weeks. There was only one episode of grade IV
      neutropenia and no episodes of grade 3-4 non-hematological toxicity were
      observed. CONCLUSION: Paclitaxel exhibited minimal activity in this patient
      population.

PMID- 11463807
TI  - High dose rate interstitial brachytherapy in soft tissue sarcoma: technical
      aspects and results.
AB  - BACKGROUND: Radiation is essential for function preservation in the management of
      soft tissue sarcoma (STS). One of the advantages of brachytherapy is that it
      allows for specific localization of radiation dose to the tumor bed. We examined
      the results of our clinical experiences with immediate postoperative high dose
      rate (HDR) brachytherapy and external beam radiation treatment (EBRT) for STS.
      METHODS: A total of 17 patients (11 primary and six recurrent) between 1995 and
      1999 were included in this review. The inclusion criteria for HDR and EBRT were
      as follows: (1) high-grade tumor, (2) low-grade tumor of > or = 10 cm, (3)
      recurrent tumor, (4) tumor abutting or invading critical structures and (5)
      positive margin. The catheters (six French) were placed parallel to the long axis
      of the tumor with a 1-1.5 cm spacing in between. If necessary, muscle or gel-foam
      was placed over the critical structures to maintain a minimum space of 0.5 cm
      from the catheters. On postoperative day 6, patients received HDR (2-3
      Gy/fraction x6, twice daily). Three weeks later, patients received EBRT (total 36
      60 Gy). The follow-up duration was between 13 and 60 months (median 31 months).
      RESULTS: There was no local failure within the radiation field in any of the
      patients. One patient required wound revision for delayed healing after
      brachytherapy. During EBRT, most patients experienced only mild erythema (grade 1
      or 2 skin reaction). In long-term follow-up, there were no patients with
      neuropathy or significant fibrosis. CONCLUSIONS: Our results suggest that
      immediate postoperative HDR with a total dose of 12-18 Gy over 3 days is an
      effective treatment combined with EBRT in the management of STS.

PMID- 11463808
TI  - Interstitial pneumonia possibly due to a novel anticancer drug, TS-1: first case
      report.
AB  - A newly approved oral fluoropyrimidine, TS-1, is a dihydropyrimide dehydrogenase
      (DPD)-inhibiting fluoropyrimidine (DIF) drug. We describe a case of interstitial
      pneumonia probably caused by TS-1. A peripheral blood lymphocytes stimulating
      test (DLST) with TS-1 demonstrated a substantial positive reaction. So far only
      three cases of TS-1-induced interstitial pneumonia have been reported but the
      relationship between interstitial pneumonia and TS-1 was demonstrated only in
      this case. Considering that interstitial pneumonia has also been reported with 5
      FU, it is necessary in the future to clarify which component of this drug is
      directly related to interstitial pneumonia.

PMID- 11463809
TI  - A nested variant of transitional cell carcinoma of the urinary bladder: a case
      report.
AB  - Nested variants of transitional cell carcinomas (TCC-NVs) are relatively rare
      neoplasms in the urinary bladder, but at least 25 cases have been described. This
      disease is characterized by the pathological finding of irregular nests and/or
      tubules of transitional carcinoma cells infiltrating the lamina propria without
      involvement of the mucosal layer. In our case, diagnosed by open biopsy, there
      were scattered tumor cells observed from the muscle layer to the subserosa, with
      a tendency toward increasing cellular anaplasia with the depth of invasion. Since
      the prognosis of TCC-NV is generally poor, comprehensive chemotherapy was
      performed. No changes were observed on computed tomography and the performance
      status (0) remained the same after 1 year, so the treatment was considered
      effective. We conclude that open biopsy should be carried out without hesitation
      when bladder cancer is suspected, even if there are negative findings of repeated
      urinary cytology examination and/or endoscopic cold cup biopsy.
      Immunohistochemical analysis may help in the diagnosis of TCC-NVs derived from
      epithelial cells. Diagnosis and treatment at an early stage should reduce the
      mortality of patients with TCC-NVs.

PMID- 11463810
TI  - Successful unrelated cord blood transplantation in Philadelphia chromosome
      positive acute lymphoblastic leukemia during pulmonary aspergillosis treated by
      anti-fungal therapy, granulocyte colony-stimulating factor-mobilized granulocytes
      and surgical resection: case report.
AB  - A 3-year-old girl with Philadelphia chromosome positive acute lymphoblastic
      leukemia developed pulmonary aspergillosis during severe neutropenia by re
      induction therapy. She was treated by intravenous fluconazole, oral itraconazole
      with plasma level monitoring and surgical resection of the focus for 3 months
      after clinical diagnosis of fungal infection was made. Once she had recovered
      from surgery we attempted to induce remission with anti-fungal treatment. She
      developed fever and neutropenia and appeared unlikely to remit with conventional
      chemotherapy. Unrelated one-antigen-mismatched cord blood (CB) transplantation
      was performed 2 months after the induction therapy. Her pulmonary aspergillosis
      was reactivated during subsequent conditioning. Anti-fungal drugs were switched
      to amphotericin B and granulocyte colony-stimulating factor-mobilized granulocyte
      concentrates were transfused. She obtained engraftment and has maintained
      complete hematological and molecular remission without signs of aspergillus
      infection for 13 months so far after transplantation. Even very high-risk
      transplantation in pediatric patients could be successfully supported by
      carefully designed intense comprehensive medical care.

PMID- 11463811
TI  - Cancer statistics Digest. Trends of all cancer in Japan [News].

PMID- 11463812
TI  - The insert region of RhoA is essential for Rho kinase activation and cellular
      transformation.
AB  - RhoA is involved in multiple cellular processes, including cytoskeletal
      organization, gene expression, and transformation. These processes are mediated
      by a variety of downstream effector proteins. However, which effectors are
      involved in cellular transformation and how these proteins are activated
      following interaction with Rho remains to be established. A unique feature that
      distinguishes the Rho family from other Ras-related GTPases is the insert region,
      which may confer Rho-specific signaling events. Here we report that deletion of
      the insert region does not result in impaired effector binding. Instead, this
      insert deletion mutant (RhoDeltaRas, in which the insert helix has been replaced
      with loop 8 of Ras) acted in a dominant inhibitory fashion to block RhoA-induced
      transformation. Since RhoDeltaRas failed to promote stress fiber formation, we
      examined the ability of this mutant to bind to and subsequently activate Rho
      kinase. Surprisingly, RhoDeltaRas-GTP coprecipitated with Rho kinase but failed
      to activate it in vivo. These data suggested that the insert domain is not
      required for Rho kinase binding but plays a role in its activation. The
      constitutively active catalytic domain of Rho kinase did not promote focus
      formation alone or in the presence of Raf(340D) but cooperated with RhoDeltaRas
      to induce cellular transformation. This suggests that Rho kinase needs to
      cooperate with additional Rho effectors to promote transformation. Further, the
      Rho kinase catalytic domain reversed the inhibitory effect of RhoDeltaRas on Rho
      induced transformation, suggesting that one of the downstream targets of Rho
      induced transformation abrogated by RhoDeltaRas is indeed Rho kinase. In
      conclusion, we have demonstrated that the insert region of RhoA is required for
      Rho kinase activation but not for binding and that this kinase activity is
      required to induce morphologic transformation of NIH 3T3 cells.

PMID- 11463813
TI  - NF-kappaB signals induce the expression of c-FLIP.
AB  - Activation of the transcription factor NF-kappaB is a major effector of the
      inducible resistance to death receptor-mediated apoptosis. Previous evidence
      indicates that the combined transcriptional activation of TRAF-1, TRAF-2, IAP-1,
      and IAP-2 is required to suppress cell death by tumor necrosis factor (TNF). Here
      we show that NF-kappaB activation upregulates the caspase 8 inhibitor FLIP,
      resulting in increased resistance to Fas ligand (FasL) or TNF. Restoration of
      either the full-length 55-kDa long form of FLIP or an alternatively spliced short
      form of FLIP in NF-kappaB null cells inhibits TNF- and FasL-induced cell death
      efficiently, whereas the expression of IAP or TRAF family members only partially
      rescues cells from death. Resistance to either FasL- or TNF-induced apoptosis is
      overcome when cells are incubated in the presence of the protein synthesis
      inhibitor cycloheximide. This treatment leads to the rapid downregulation of FLIP
      but not to that of TRAF2. Our findings suggest that FLIP is an important mediator
      of NF-kappaB-controlled antiapoptotic signals.

PMID- 11463814
TI  - Functional analysis of mouse kinesin motor Kif3C.
AB  - Members of the kinesin II family are thought to play essential roles in many
      types of intracellular transport. One distinguishing feature of kinesin II is
      that it generally contains two different motor subunits from the Kif3 family.
      Three Kif3 family members (Kif3A, Kif3B, and Kif3C) have been identified and
      characterized in mice. Intracellular localization and biochemical studies
      previously suggested that Kif3C is an anterograde motor involved in anterograde
      axonal transport. To understand the in vivo function of the Kif3C gene, we used
      homologous recombination in embryonic stem cells to construct two different
      knockout mouse strains for the Kif3C gene. Both homozygous Kif3C mutants are
      viable, reproduce normally, and apparently develop normally. These results
      suggest that Kif3C is dispensable for normal neural development and behavior in
      the mouse.

PMID- 11463815
TI  - Interaction between acetylated MyoD and the bromodomain of CBP and/or p300.
AB  - Acetylation is emerging as a posttranslational modification of nuclear proteins
      that is essential to the regulation of transcription and that modifies
      transcription factor affinity for binding sites on DNA, stability, and/or nuclear
      localization. Here, we present both in vitro and in vivo evidence that
      acetylation increases the affinity of myogenic factor MyoD for acetyltransferases
      CBP and p300. In myogenic cells, the fraction of endogenous MyoD that is
      acetylated was found associated with CBP or p300. In vitro, the interaction
      between MyoD and CBP was more resistant to high salt concentrations and was
      detected with lower doses of MyoD when MyoD was acetylated. Interestingly, an
      analysis of CBP mutants revealed that the interaction with acetylated MyoD
      involves the bromodomain of CBP. In live cells, MyoD mutants that cannot be
      acetylated did not associate with CBP or p300 and were strongly impaired in their
      ability to cooperate with CBP for transcriptional activation of a muscle creatine
      kinase-luciferase construct. Taken together, our data suggest a new mechanism for
      activation of protein function by acetylation and demonstrate for the first time
      an acetylation-dependent interaction between the bromodomain of CBP and a
      nonhistone protein.

PMID- 11463816
TI  - Mice with very low expression of the vesicular monoamine transporter 2 gene
      survive into adulthood: potential mouse model for parkinsonism.
AB  - We have created a transgenic mouse with a hypomorphic allele of the vesicular
      monoamine transporter 2 (Vmat2) gene by gene targeting. These mice (KA1) have
      profound changes in monoamine metabolism and function and survive into adulthood.
      Specifically, these animals express very low levels of VMAT2, an endogenous
      protein which sequesters monoamines intracellularly into vesicles, a process
      that, in addition to being important in normal transmission, may also act to keep
      intracellular levels of the monoamine neurotransmitters below potentially toxic
      thresholds. Homozygous mice show large reductions in brain tissue monoamines,
      motor impairments, enhanced sensitivity to dopamine agonism, and changes in the
      chemical neuroanatomy of the striatum that are consistent with alterations in the
      balance of the striatonigral (direct) and striatopallidal (indirect) pathways.
      The VMAT2-deficient KA1 mice are also more vulnerable to the neurotoxic effects
      of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in terms of nigral dopamine cell
      death. We suggest that the mice may be of value in examining, long term, the
      insidious damaging consequences of abnormal intracellular handling of monoamines.
      On the basis of our current findings, the mice are likely to prove of immediate
      interest to aspects of the symptomatology of parkinsonism. They may also,
      however, be of use in probing other aspects of monoaminergic function and
      dysfunction in the brain, the latter making important contributions to the
      pathogenesis of schizophrenia and addiction.

PMID- 11463817
TI  - Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin
      and Hic-5 through interaction with focal adhesion kinase.
AB  - Hic-5 is a paxillin homologue that is localized to focal adhesion complexes. Hic
      5 and paxillin share structural homology and interacting factors such as focal
      adhesion kinase (FAK), Pyk2/CAKbeta/RAFTK, and PTP-PEST. Here, we showed that Hic
      5 inhibits integrin-mediated cell spreading on fibronectin in a competitive
      manner with paxillin in NIH 3T3 cells. The overexpression of Hic-5 sequestered
      FAK from paxillin, reduced tyrosine phosphorylation of paxillin and FAK, and
      prevented paxillin-Crk complex formation. In addition, Hic-5-mediated inhibition
      of spreading was not observed in mouse embryo fibroblasts (MEFs) derived from
      FAK(-/-) mice. The activity of c-Src following fibronectin stimulation was
      decreased by about 30% in Hic-5-expressing cells, and the effect of Hic-5 was
      restored by the overexpression of FAK and the constitutively active forms of Rho
      family GTPases, Rac1 V12 and Cdc42 V12, but not RhoA V14. These observations
      suggested that Hic-5 inhibits cell spreading through competition with paxillin
      for FAK and subsequent prevention of downstream signal transduction. Moreover,
      expression of antisense Hic-5 increased spreading in primary MEFs. These results
      suggested that the counterbalance of paxillin and Hic-5 expression may be a novel
      mechanism regulating integrin-mediated signal transduction.

PMID- 11463818
TI  - Antiapoptotic signaling generated by caspase-induced cleavage of RasGAP.
AB  - Activation of caspases 3 and 9 is thought to commit a cell irreversibly to
      apoptosis. There are, however, several documented situations (e.g., during
      erythroblast differentiation) in which caspases are activated and caspase
      substrates are cleaved with no associated apoptotic response. Why the cleavage of
      caspase substrates leads to cell death in certain cases but not in others is
      unclear. One possibility is that some caspase substrates generate antiapoptotic
      signals when cleaved. Here we show that RasGAP is one such protein. Caspases
      cleave RasGAP into a C-terminal fragment (fragment C) and an N-terminal fragment
      (fragment N). Fragment C expressed alone induces apoptosis, but this effect could
      be totally blocked by fragment N. Fragment N could also block apoptosis induced
      by low levels of caspase 9. As caspase activity increases, fragment N is further
      cleaved into fragments N1 and N2. Apoptosis induced by high levels of caspase 9
      or by cisplatin was strongly potentiated by fragment N1 or N2 but not by fragment
      N. The present study supports a model in which RasGAP functions as a sensor of
      caspase activity to determine whether or not a cell should survive. When caspases
      are mildly activated, the partial cleavage of RasGAP protects cells from
      apoptosis. When caspase activity reaches levels that allow completion of RasGAP
      cleavage, the resulting RasGAP fragments turn into potent proapoptotic molecules.

PMID- 11463819
TI  - SIR functions are required for the toleration of an unrepaired double-strand
      break in a dispensable yeast chromosome.
AB  - Unrepaired DNA double-strand breaks (DSBs) typically result in G(2) arrest. Cell
      cycle progression can resume following repair of the DSBs or through adaptation
      to the checkpoint, even if the damage remains unrepaired. We developed a screen
      for factors in the yeast Saccharomyces cerevisiae that affect checkpoint control
      and/or viability in response to a single, unrepairable DSB that is induced by HO
      endonuclease in a dispensable yeast artificial chromosome containing human DNA.
      SIR2, -3, or -4 mutants exhibit a prolonged, RAD9-dependent G(2) arrest in
      response to the unrepairable DSB followed by a slow adaptation to the persistent
      break, leading to division and rearrest in the next G(2). There are a small
      number of additional cycles before permanent arrest as microcolonies. Thus, SIR
      genes, which repress silent mating type gene expression, are required for the
      adaptation and the prevention of indirect lethality resulting from an
      unrepairable DSB in nonessential DNA. Rapid adaptation to the G(2) checkpoint and
      high viability were restored in sir(-) strains containing additional deletions of
      the silent mating type loci HML and HMR, suggesting that genes under mating type
      control can reduce the toleration of a single DSB. However, coexpression of MATa1
      and MATalpha2 in Sir(+) haploid cells did not lead to lethality from the HO
      induced DSB, suggesting that toleration of an unrepaired DSB requires more than
      one Sir(+) function.

PMID- 11463820
TI  - The Sgs1 helicase of Saccharomyces cerevisiae inhibits retrotransposition of Ty1
      multimeric arrays.
AB  - Ty1 retrotransposons in the yeast Saccharomyces cerevisiae are maintained in a
      genetically competent but transpositionally dormant state. When located in the
      ribosomal DNA (rDNA) locus, Ty1 elements are transcriptionally silenced by the
      specialized heterochromatin that inhibits rDNA repeat recombination. In addition,
      transposition of all Ty1 elements is repressed at multiple posttranscriptional
      levels. Here, we demonstrate that Sgs1, a RecQ helicase required for genome
      stability, inhibits the mobility of Ty1 elements by a posttranslational
      mechanism. Using an assay for the mobility of Ty1 cDNA via integration or
      homologous recombination, we found that the mobility of both euchromatic and rDNA
      Ty1 elements was increased 32- to 79-fold in sgs1Delta mutants. Increased Ty1
      mobility was not due to derepression of silent rDNA-Ty1 elements, since deletion
      of SGS1 reduced the mitotic stability of rDNA-Ty1 elements but did not stimulate
      their transcription. Furthermore, deletion of SGS1 did not significantly increase
      the levels of total Ty1 RNA, protein, or cDNA and did not alter the level or
      specificity of Ty1 integration. Instead, Ty1 cDNA molecules recombined at a high
      frequency in sgs1Delta mutants, resulting in transposition of heterogeneous Ty1
      multimers. Formation of Ty1 multimers required the homologous recombination
      protein Rad52 but did not involve recombination between Ty1 cDNA and genomic Ty1
      elements. Therefore, Ty1 multimers that transpose at a high frequency in
      sgs1Delta mutants are formed by intermolecular recombination between
      extrachromosomal Ty1 cDNA molecules before or during integration. Our data
      provide the first evidence that the host cell promotes retrotransposition of
      monomeric Ty1 elements by repressing cDNA recombination.

PMID- 11463821
TI  - Disruption of gamma-glutamyl leukotrienase results in disruption of leukotriene
      D(4) synthesis in vivo and attenuation of the acute inflammatory response.
AB  - To study the function of gamma-glutamyl leukotrienase (GGL), a newly identified
      member of the gamma-glutamyl transpeptidase (GGT) family, we generated null
      mutations in GGL (GGL(tm1)) and in both GGL and GGT (GGL(tm1)-GGT(tm1)) by a
      serial targeting strategy using embryonic stem cells. Mice homozygous for
      GGL(tm1) show no obvious phenotypic changes. Mice deficient in both GGT and GGL
      have a phenotype similar to the GGT-deficient mice, but approximately 70% of
      these mice die before 4 weeks of age, at least 2 months earlier than mice
      deficient only in GGT. These double-mutant mice are unable to cleave leukotriene
      C(4) (LTC(4)) to LTD(4), indicating that this conversion is completely dependent
      on the two enzymes, and in some organs (spleen and uterus) deletion of GGL alone
      abolished more than 90% of this activity. In an experimental model of
      peritonitis, GGL alone is responsible for the generation of peritoneal LTD(4).
      Further, during the development of peritonitis, GGL-deficient mice show an
      attenuation in neutrophil recruitment but not of plasma protein influx. These
      findings demonstrate an important role for GGL in the inflammatory response and
      suggest that LTC(4) and LTD(4) have distinctly different functions in the
      inflammatory process.

PMID- 11463822
TI  - Nucleocytoplasmic distribution of the ovalbumin serpin PI-9 requires a
      nonconventional nuclear import pathway and the export factor Crm1.
AB  - Proteinase inhibitor 9 (PI-9) is a human serpin present in the cytoplasm of
      cytotoxic lymphocytes and epithelial cells. It inhibits the cytotoxic lymphocyte
      granule proteinase granzyme B (graB) and is thought to protect cytotoxic
      lymphocytes and bystander cells from graB-mediated apoptosis. Following uptake
      into cells, graB promotes DNA degradation, rapidly translocating to the nucleus,
      where it binds a nuclear component. PI-9 should therefore be found in cytotoxic
      lymphocyte and bystander cell nuclei to ensure complete protection against graB.
      Here we demonstrate by microscopy and subcellular fractionation experiments that
      PI-9 is present in the nuclei of human cytotoxic cells, endothelial cells, and
      epithelial cells. We also show that the related serpins, PI-6, monocyte
      neutrophil elastase inhibitor (MNEI), PI-8, plasminogen activator inhibitor 2
      (PAI-2), and the viral serpin CrmA exhibit similar nucleocytoplasmic
      distributions. Because these serpins lack classical nuclear localization signals
      and are small enough to diffuse through nuclear pores, we investigated whether
      import occurs actively or passively. Large (approximately 70 kDa) chimeric
      proteins comprising PI-9, PI-6, PI-8, MNEI, or PAI-2 fused to green fluorescent
      protein (GFP) show similar nucleocytoplasmic distributions to the parent
      proteins, indicating that nuclear import is active. By contrast, CrmA-GFP is
      excluded from nuclei, indicating that CrmA is not actively imported. In vitro
      nuclear transport assays show that PI-9 accumulates at a rate above that of
      passive diffusion, that it requires cytosolic factors but not ATP, and that it
      does not bind an intranuclear component. Furthermore, PI-9 is exported from
      nuclei via a leptomycin B-sensitive pathway, implying involvement of the export
      factor Crm1p. We conclude that the nucleocytoplasmic distribution of PI-9 and
      related serpins involves a nonconventional nuclear import pathway and Crm1p.

PMID- 11463823
TI  - Polynucleotide phosphorylase functions as both an exonuclease and a poly(A)
      polymerase in spinach chloroplasts.
AB  - The molecular mechanism of mRNA degradation in the chloroplast consists of
      sequential events including endonucleolytic cleavage, the addition of poly(A)
      rich sequences to the endonucleolytic cleavage products, and exonucleolytic
      degradation by polynucleotide phosphorylase (PNPase). In Escherichia coli,
      polyadenylation is performed mainly by poly(A)-polymerase (PAP) I or by PNPase in
      its absence. While trying to purify the chloroplast PAP by following in vitro
      polyadenylation activity, it was found to copurify with PNPase and indeed could
      not be separated from it. Purified PNPase was able to polyadenylate RNA molecules
      with an activity similar to that of lysed chloroplasts. Both activities use ADP
      much more effectively than ATP and are inhibited by stem-loop structures. The
      activity of PNPase was directed to RNA degradation or polymerization by
      manipulating physiologically relevant concentrations of P(i) and ADP. As expected
      of a phosphorylase, P(i) enhanced degradation, whereas ADP inhibited degradation
      and enhanced polymerization. In addition, searching the complete Arabidopsis
      genome revealed several putative PAPs, none of which were preceded by a typical
      chloroplast transit peptide. These results suggest that there is no enzyme
      similar to E. coli PAP I in spinach chloroplasts and that polyadenylation and
      exonucleolytic degradation of RNA in spinach chloroplasts are performed by one
      enzyme, PNPase.

PMID- 11463824
TI  - Histone H1 phosphorylation by Cdk2 selectively modulates mouse mammary tumor
      virus transcription through chromatin remodeling.
AB  - Transcriptional activation of the mouse mammary tumor virus (MMTV) promoter by
      ligand-bound glucocorticoid receptor (GR) is transient. Previously, we
      demonstrated that prolonged hormone exposure results in displacement of the
      transcription factor nuclear factor 1 (NF1) and the basal transcription complex
      from the promoter, the dephosphorylation of histone H1, and the establishment of
      a repressive chromatin structure. We have explored the mechanistic link between
      histone H1 dephosphorylation and silencing of the MMTV promoter by describing the
      putative kinase responsible for H1 phosphorylation. Both in vitro kinase assays
      and in vivo protein expression studies suggest that in hormone-treated cells the
      ability of cdk2 to phosphorylate histone H1 is decreased and the cdk2 inhibitory
      p21 protein level is increased. To address the role of cdk2 and histone H1
      dephosphorylation in the silencing of the MMTV promoter, we used potent cdk2
      inhibitors, Roscovitine and CVT-313, to generate an MMTV promoter which is
      associated predominantly with the dephosphorylated form of histone H1. Both
      Roscovitine and CVT-313 block phosphorylation of histone H1 and, under these
      conditions, the GR is unable to remodel chromatin, recruit transcription factors
      to the promoter, or stimulate MMTV mRNA accumulation. These results suggest a
      model where cdk2-directed histone H1 phosphorylation is a necessary condition to
      permit GR-mediated chromatin remodeling and activation of the MMTV promoter in
      vivo.

PMID- 11463825
TI  - DNA methylation is linked to deacetylation of histone H3, but not H4, on the
      imprinted genes Snrpn and U2af1-rs1.
AB  - The relationship between DNA methylation and histone acetylation at the imprinted
      mouse genes U2af1-rs1 and Snrpn is explored by chromatin immunoprecipitation
      (ChIP) and resolution of parental alleles using single-strand conformational
      polymorphisms. The U2af1-rs1 gene lies within a differentially methylated region
      (DMR), while Snrpn has a 5' DMR (DMR1) with sequences homologous to the
      imprinting control center of the Prader-Willi/Angelman region. For both DMR1 of
      Snrpn and the 5' untranslated region (5'-UTR) and 3'-UTR of U2af1-rs1, the
      methylated and nonexpressed maternal allele was underacetylated, relative to the
      paternal allele, at all H3 lysines tested (K14, K9, and K18). For H4,
      underacetylation of the maternal allele was exclusively (U2af1-rs1) or
      predominantly (Snrpn) at lysine 5. Essentially the same patterns of differential
      acetylation were found in embryonic stem (ES) cells, embryo fibroblasts, and
      adult liver from F1 mice and in ES cells from mice that were dipaternal or
      dimaternal for U2af1-rs1. In contrast, in a region within Snrpn that has
      biallelic methylation in the cells and tissues analyzed, the paternal (expressed)
      allele showed relatively increased acetylation of H4 but not of H3. The methyl
      CpG-binding-domain (MBD) protein MeCP2 was found, by ChIP, to be associated
      exclusively with the maternal U2af1-rs1 allele. To ask whether DNA methylation is
      associated with histone deacetylation, we produced mice with transgene-induced
      methylation at the paternal allele of U2af1-rs1. In these mice, H3 was
      underacetylated across both the parental U2af1-rs1 alleles whereas H4 acetylation
      was unaltered. Collectively, these data are consistent with the hypothesis that
      CpG methylation leads to deacetylation of histone H3, but not H4, through a
      process that involves selective binding of MBD proteins.

PMID- 11463826
TI  - Inhibition of the motility and growth of B16F10 mouse melanoma cells by dominant
      negative mutants of Dok-1.
AB  - Dok-1 (p62(Dok)) is a multiple-site docking protein that acts downstream of
      receptor and nonreceptor tyrosine kinases. Although it has been proposed to
      contribute to the control of cell growth and migration through association with
      the Ras GTPase-activating protein and the adapter protein Nck, the role of Dok-1
      remains largely unknown. The functions of Dok-1 have now been investigated by the
      generation of two different COOH-terminal truncation mutants of this protein: one
      (DokPH+PTB) containing the pleckstrin homology and phosphotyrosine-binding
      domains, and the other (DokPH) composed only of the pleckstrin homology domain.
      Both of these mutant proteins were shown to act in a dominant negative manner.
      Overexpression of each of the mutants in highly metastatic B16F10 mouse melanoma
      cells thus both inhibited the tyrosine phosphorylation of endogenous Dok-1
      induced by cell adhesion as well as reduced the association of the endogenous
      protein with cellular membranes and the cytoskeleton. Overexpression of DokPH+PTB
      in these cells also markedly reduced both the rates of cell spreading, migration,
      and growth as well as the extent of Ras activation. The effects of DokPH on these
      processes were less pronounced than were those of DokPH+PTB, indicating the
      importance of the phosphotyrosine-binding domain. These results suggest that at
      least in B16F10 cells, Dok-1 positively regulates not only cell spreading and
      migration but also cell growth and Ras activity.

PMID- 11463827
TI  - Regulation of Id gene expression by type I insulin-like growth factor: roles of
      Stat3 and the tyrosine 950 residue of the receptor.
AB  - Id proteins are known to play important roles in the proliferation and
      differentiation of many cell types. The type 1 insulin-like growth factor
      receptor (IGF-IR), activated by its ligand, induces the differentiation of 32D
      IGF-IR cells, a murine hematopoietic cell line, expressing a human IGF-IR.
      Expression in 32D IGF-IR cells of a dominant negative mutant of Stat3 (DNStat3)
      inhibits IGF-I-mediated differentiation. DNStat3 causes a dramatic increase in
      Id2 gene expression. This increase, however, is IGF-I dependent and is abrogated
      by a mutation at tyrosine 950 of the IGF-IR. These results indicate that in 32D
      cells, the IGF-IR regulates the expression of the Id2 gene and that this
      regulation is modulated by both positive and negative signals. Our results also
      suggest that in this model, Id2 proteins influence the differentiation program of
      cells but are not sufficient for the full stimulation of their proliferation
      program.

PMID- 11463828
TI  - High-copy-number expression of Sub2p, a member of the RNA helicase superfamily,
      suppresses hpr1-mediated genomic instability.
AB  - We report on a novel role for a pre-mRNA splicing component in genome stability.
      The Hpr1 protein, a component of an RNA polymerase II complex and required for
      transcription elongation, is also required for genome stability. Deletion of HPR1
      results in a 1,000-fold increase in genome instability, detected as direct-repeat
      instability. This instability can be suppressed by the high-copy-number SUB2
      gene, which is the Saccharomyces cerevisiae homologue of the human splicing
      factor hUAP56. Although SUB2 is essential, conditional alleles grown at the
      permissive temperature complement the essential function of SUB2 yet reveal
      nonessential phenotypes. These studies have uncovered a role for SUB2 in
      preventing genome instability. The genomic instability observed in sub2 mutants
      can be suppressed by high-copy-number HPR1. A deletion mutant of CDC73, a
      component of a PolII complex, is also unstable for direct repeats. This too is
      suppressed by high-copy-number SUB2. Thus, defects in both the transcriptional
      machinery and the pre-mRNA splicing machinery can be sources of genome
      instability. The ability of a pre-mRNA splicing factor to suppress the
      hyperrecombination phenotype of a defective PolII complex raises the possibility
      of integrating transcription, RNA processing, and genome stability or a second
      role for SUB2.

PMID- 11463829
TI  - Reduced hepatic uptake and intestinal excretion of organic cations in mice with a
      targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene.
AB  - The polyspecific organic cation transporter 1 (OCT1 [SLC22A1]) mediates
      facilitated transport of small (hydrophilic) organic cations. OCT1 is localized
      at the basolateral membrane of epithelial cells in the liver, kidney, and
      intestine and could therefore be involved in the elimination of endogenous amines
      and xenobiotics via these organs. To investigate the pharmacologic and
      physiologic role of this transport protein, we generated Oct1 knockout (Oct1(-/
      )) mice. Oct1(-/-) mice appeared to be viable, healthy, and fertile and displayed
      no obvious phenotypic abnormalities. The role of Oct1 in the pharmacology of
      substrate drugs was studied by comparing the distribution and excretion of the
      model substrate tetraethylammonium (TEA) after intravenous administration to wild
      type and Oct1(-/-) mice. In Oct1(-/-) mice, accumulation of TEA in liver was four
      to sixfold lower than in wild-type mice, whereas direct intestinal excretion of
      TEA was reduced about twofold. Excretion of TEA into urine over 1 h was 53% of
      the dose in wild-type mice, compared to 80% in knockout mice, probably because in
      Oct1(-/-) mice less TEA accumulates in the liver and thus more is available for
      rapid excretion by the kidney. In addition, we found that absence of Oct1 leads
      to decreased liver accumulation of the anticancer drug metaiodobenzylguanidine
      and the neurotoxin 1-methyl-4-phenylpyridium. In conclusion, our data show that
      Oct1 plays an important role in the uptake of organic cations into the liver and
      in their direct excretion into the lumen of the small intestine.

PMID- 11463830
TI  - Loss of JunB activity enhances stromelysin 1 expression in a model of the
      epithelial-to-mesenchymal transition of mouse skin tumors.
AB  - Chemical carcinogenesis in mouse skin has been useful in delineating the
      molecular events that underlie squamous cell carcinoma progression. A late event
      in this progression, the epithelial-to-mesenchymal transition (EMT), is
      characterized by the loss of epithelial markers and the presence of mesenchymal
      markers. One mesenchymal marker associated with this transition is the matrix
      metalloproteinase stromelysin 1 (Str-1). To examine the molecular mechanisms
      regulating the expression of Str-1 during the EMT, genetically related mouse skin
      tumor cell lines representing the epithelial (B9(SQ)) and mesenchymal (A5(SP))
      phenotypes were studied. As expected, B9(SQ) cells did not make Str-1, while
      A5(SP) cells did. B9(SQ)-A5(SP) somatic hybrids did not make Str-1, suggesting
      that a critical regulatory factor was a B9(SQ)-specific repressor. Str-1 promoter
      analysis revealed that a canonical AP-1 site was sufficient to maintain
      differential reporter gene activity. This result correlated with the observed
      loss of binding of the transcriptionally inactive JunB-Fra-2 AP-1 complex from
      B9(SQ) cells, being replaced primarily by the more active JunD-Fra-2 complex in
      A5(SP) cells. The higher level of JunB binding to both DNA and Fra-2 correlated
      with its hyperphosphorylation by Jun N-terminal kinase, an activity that was
      significantly higher in B9(SQ) cells. In the somatic hybrids, JunB gene
      expression was highly upregulated, a condition that also was sufficient to
      repress the expression of the endogenous Str-1 gene in A5(SP) cells. These data
      suggested that alterations in JunB activity, by changes in either phosphorylation
      or gene expression, contributed to the phenotypic differences that occur in this
      model of the EMT.

PMID- 11463831
TI  - Oncogenic Ras blocks anoikis by activation of a novel effector pathway
      independent of phosphatidylinositol 3-kinase.
AB  - Activated Ras, but not Raf, causes transformation of RIE-1 rat intestinal
      epithelial cells, demonstrating the importance of Raf-independent effector
      signaling in mediating Ras transformation. To further assess the contribution of
      Raf-dependent and Raf-independent function in oncogenic Ras transformation, we
      evaluated the mechanism by which oncogenic Ras blocks suspension-induced
      apoptosis, or anoikis, of RIE-1 cells. We determined that oncogenic versions of H
      , K-, and N-Ras, as well as the Ras-related proteins TC21 and R-Ras, protected
      RIE-1 cells from anoikis. Surprisingly, our analyses of Ras effector domain
      mutants or constitutively activated effectors indicated that activation of Raf-1,
      phosphatidylinositol 3-kinase (PI3K), or RalGDS alone is not sufficient to
      promote Ras inhibition of anoikis. Treatment of Ras-transformed cells with the
      U0126 MEK inhibitor caused partial reversion to an anoikis-sensitive state,
      indicating that extracellular signal-regulated kinase activation contributes to
      inhibition of anoikis. Unexpectedly, oncogenic Ras failed to activate Akt, and
      treatment of Ras-transformed RIE-1 cells with the LY294002 PI3K inhibitor did not
      affect anoikis resistance or growth in soft agar. Thus, while important for Ras
      transformation of fibroblasts, PI3K may not be involved in Ras transformation of
      RIE-1 cells. Finally, inhibition of epidermal growth factor receptor kinase
      activity did not overcome Ras inhibition of anoikis, indicating that this
      autocrine loop essential for transformation is not involved in anoikis
      protection. We conclude that a PI3K- and RalGEF-independent Ras effector(s)
      likely cooperates with Raf to confer anoikis resistance upon RIE-1 cells, thus
      underscoring the complex nature by which Ras transforms cells.

PMID- 11463832
TI  - Negative regulation of protein translation by mitogen-activated protein kinase
      interacting kinases 1 and 2.
AB  - Eukaryotic initiation factor 4E (eIF4E) is a key component of the translational
      machinery and an important modulator of cell growth and proliferation. The
      activity of eIF4E is thought to be regulated by interaction with inhibitory
      binding proteins (4E-BPs) and phosphorylation by mitogen-activated protein (MAP)
      kinase-interacting kinase (MNK) on Ser209 in response to mitogens and cellular
      stress. Here we demonstrate that phosphorylation of eIF4E via MNK1 is mediated
      via the activation of either the Erk or p38 pathway. We further show that
      expression of active mutants of MNK1 and MNK2 in 293 cells diminishes cap
      dependent translation relative to cap-independent translation in a transient
      reporter assay. The same effect on cap-dependent translation was observed when
      MNK1 was activated by the Erk or p38 pathway. In line with these findings,
      addition of recombinant active MNK1 to rabbit reticulocyte lysate resulted in a
      reduced protein synthesis in vitro, and overexpression of MNK2 caused a decreased
      rate of protein synthesis in 293 cells. By using CGP 57380, a novel low-molecular
      weight kinase inhibitor of MNK1, we demonstrate that eIF4E phosphorylation is not
      crucial to the formation of the initiation complex, mitogen-stimulated increase
      in cap-dependent translation, and cell proliferation. Our results imply that
      activation of MNK by MAP kinase pathways does not constitute a positive
      regulatory mechanism to cap-dependent translation. Instead, we propose that the
      kinase activity of MNKs, eventually through phosphorylation of eIF4E, may serve
      to limit cap-dependent translation under physiological conditions.

PMID- 11463833
TI  - Nonsense-mediated decay of human HEXA mRNA.
AB  - Nonsense-mediated mRNA decay (NMD), the loss of mRNAs carrying premature stop
      codons, is a process by which cells recognize and degrade nonsense mRNAs to
      prevent possibly toxic effects of truncated peptides. Most mammalian nonsense
      mRNAs are degraded while associated with the nucleus, but a few are degraded in
      the cytoplasm; at either site, there is a requirement for translation and for an
      intron downstream of the early stop codon. We have examined the NMD of a mutant
      HEXA message in lymphoblasts derived from a Tay-Sachs disease patient homozygous
      for the common frameshift mutation 1278ins4. The mutant mRNA was nearly
      undetectable in these cells and increased to approximately 40% of normal in the
      presence of the translation inhibitor cycloheximide. The stabilized transcript
      was found in the cytoplasm in association with polysomes. Within 5 h of
      cycloheximide removal, the polysome-associated nonsense message was completely
      degraded, while the normal message was stable. The increased lability of the
      polysome-associated mutant HEXA mRNA shows that NMD of this endogenous mRNA
      occurred in the cytoplasm. Transfection of Chinese hamster ovary cells showed
      that expression of an intronless HEXA minigene harboring the frameshift mutation
      or a closely located nonsense codon resulted in half the normal mRNA level.
      Inclusion of multiple downstream introns decreased the abundance further, to
      about 20% of normal. Thus, in contrast to other systems, introns are not
      absolutely required for NMD of HEXA mRNA, although they enhance the low-HEXA-mRNA
      phenotype.

PMID- 11463834
TI  - The oncoprotein Tax binds the SRC-1-interacting domain of CBP/p300 to mediate
      transcriptional activation.
AB  - Oncogenesis associated with human T-cell leukemia virus (HTLV) infection is
      directly linked to the virally encoded transcription factor Tax. To activate HTLV
      1 transcription Tax interacts with the cellular protein CREB and the pleiotropic
      coactivators CBP and p300. While extensively studied, the molecular mechanisms of
      Tax transcription function and coactivator utilization are not fully understood.
      Previous studies have focused on Tax binding to the KIX domain of CBP, as this
      was believed to be the key step in recruiting the coactivator to the HTLV-1
      promoter. In this study, we identify a carboxy-terminal region of CBP (and p300)
      that strongly interacts with Tax and mediates Tax transcription function. Through
      deletion mutagenesis, we identify amino acids 2003 to 2212 of CBP, which we call
      carboxy-terminal region 2 (CR2), as the minimal region for Tax interaction.
      Interestingly, this domain corresponds to the steroid receptor coactivator 1 (SRC
      1)-interacting domain of CBP. We show that a double point mutant targeted to one
      of the putative alpha-helical motifs in this domain significantly compromises the
      interaction with Tax. We also characterize the region of Tax responsible for
      interaction with CR2 and show that the previously identified transactivation
      domain of Tax (amino acids 312 to 319) participates in CR2 binding. This region
      of Tax corresponds to a consensus amphipathic helix, and single point mutations
      targeted to amino acids on the face of this helix abolish interaction with CR2
      and dramatically reduce Tax transcription function. Finally, we demonstrate that
      Tax and SRC-1 bind to CR2 in a mutually exclusive fashion. Together, these
      studies identify a novel Tax-interacting site on CBP/p300 and extend our
      understanding of the molecular mechanism of Tax transactivation.

PMID- 11463835
TI  - Reconstitution of enhancer function in paternal pronuclei of one-cell mouse
      embryos.
AB  - How chromatin-mediated transcription regulates the beginning of mammalian
      development is currently unknown. Factors responsible for promoter repression and
      enhancer-mediated relief of this repression are not present in the paternal
      pronuclei of one-cell mouse embryos but are present in the zygotic nuclei of two
      cell embryos. Here we show that coinjection of purified histones and a plasmid
      encoded reporter gene into the paternal pronuclei of one-cell embryos at a
      specific histone-DNA concentration could recreate the behavior observed in two
      cell embryos: acquisition of promoter repression and subsequent relief of this
      repression either by functional enhancers or by histone deacetylase inhibitors.
      Furthermore, the extent of enhancer-mediated stimulation in one-cell embryos
      depended on the acetylation status of the injected histones, on the treatment of
      embryos with a histone deacetylase inhibitor, and on the developmentally
      regulated appearance of enhancer-specific coactivator activity. The coinjected
      plasmids in one-cell embryos also exhibited chromatin assembly, as determined by
      a supercoiling assay. Thus, injection of histones into one-cell embryos
      faithfully reproduced the chromatin-mediated transcription observed in two-cell
      embryos. These results suggest that the need for enhancers to stimulate promoters
      through relief of chromatin-mediated repression occurs once the parental genomes
      are organized into chromatin. Furthermore, we present a model mammalian system in
      which the role of individual histones, and particular domains within the histones
      that are targeted in enhancer function, can be examined using purified mutant
      histones.

PMID- 11463836
TI  - Yeast RNA polymerase I enhancer is dispensable for transcription of the
      chromosomal rRNA gene and cell growth, and its apparent transcription enhancement
      from ectopic promoters requires Fob1 protein.
AB  - At the end of the 35S rRNA gene within ribosomal DNA (rDNA) repeats in
      Saccharomyces cerevisiae lies an enhancer that has been shown to greatly
      stimulate rDNA transcription in ectopic reporter systems. We found, however, that
      the enhancer is not necessary for normal levels of rRNA synthesis from
      chromosomal rDNA or for cell growth. Yeast strains which have the entire enhancer
      from rDNA deleted did not show any defects in growth or rRNA synthesis. We found
      that the stimulatory activity of the enhancer for ectopic reporters is not
      observed in cells with disrupted nucleolar structures, suggesting that reporter
      genes are in general poorly accessible to RNA polymerase I (Pol I) machinery in
      the nucleolus and that the enhancer improves accessibility. We also found that a
      fob1 mutation abolishes transcription from the enhancer-dependent rDNA promoter
      integrated at the HIS4 locus without any effect on transcription from chromosomal
      rDNA. FOB1 is required for recombination hot spot (HOT1) activity, which also
      requires the enhancer region, and for recombination within rDNA repeats. We
      suggest that Fob1 protein stimulates interactions between rDNA repeats through
      the enhancer region, thus helping ectopic rDNA promoters to recruit the Pol I
      machinery normally present in the nucleolus.

PMID- 11463837
TI  - Protein kinase C-delta regulates thrombin-induced ICAM-1 gene expression in
      endothelial cells via activation of p38 mitogen-activated protein kinase.
AB  - The procoagulant thrombin promotes the adhesion of polymorphonuclear leukocytes
      to endothelial cells by a mechanism involving expression of intercellular
      adhesion molecule 1 (ICAM-1) via an NF-kappaB-dependent pathway. We now provide
      evidence that protein kinase C-delta (PKC-delta) and the p38 mitogen-activated
      protein (MAP) kinase pathway play a critical role in the mechanism of thrombin
      induced ICAM-1 gene expression in endothelial cells. We observed the
      phosphorylation of PKC-delta and p38 MAP kinase within 1 min after thrombin
      challenge of human umbilical vein endothelial cells. Pretreatment of these cells
      with the PKC-delta inhibitor rottlerin prevented the thrombin-induced
      phosphorylation of p38 MAP kinase, suggesting that p38 MAP kinase signals
      downstream of PKC-delta. Inhibition of PKC-delta or p38 MAP kinase by
      pharmacological and genetic approaches markedly decreased the thrombin-induced NF
      kappaB activity and resultant ICAM-1 expression. The effects of PKC-delta
      inhibition were secondary to inhibition of IKKbeta activation and of subsequent
      NF-kappaB binding to the ICAM-1 promoter. The effects of p38 MAP kinase
      inhibition occurred downstream of IkappaBalpha degradation without affecting the
      DNA binding function of nuclear NF-kappaB. Thus, PKC-delta signals thrombin
      induced ICAM-1 gene transcription by a dual mechanism involving activation of
      IKKbeta, which mediates NF-kappaB binding to the ICAM-1 promoter, and p38 MAP
      kinase, which enhances transactivation potential of the bound NF-kappaB p65
      (RelA).

PMID- 11463838
TI  - Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results
      in bare lymphocyte syndrome.
AB  - Ankyrin repeats are well-known structural modules that mediate interactions
      between a wide spectrum of proteins. The regulatory factor X with ankyrin repeats
      (RFXANK) is a subunit of a tripartite RFX complex that assembles on promoters of
      major histocompatibility complex class II (MHC II) genes. Although it is known
      that RFXANK plays a central role in the nucleation of RFX, it was not clear how
      its ankyrin repeats mediate the interactions within the complex and with other
      proteins. To answer this question, we modeled the RFXANK protein and determined
      the variable residues of the ankyrin repeats that should contact other proteins.
      Site-directed alanine mutagenesis of these residues together with in vitro and in
      vivo binding studies elucidated how RFXAP and CIITA, which simultaneously
      interact with RFXANK in vivo, bind to two opposite faces of its ankyrin repeats.
      Moreover, the binding of RFXAP requires two separate surfaces on RFXANK. One of
      them, which is located in the ankyrin groove, is severely affected in the FZA
      patient with the bare lymphocyte syndrome. This genetic disease blocks the
      expression of MHC II molecules on the surface of B cells. By pinpointing the
      interacting residues of the ankyrin repeats of RFXANK, the mechanism of this
      subtype of severe combined immunodeficiency was revealed.

PMID- 11463839
TI  - Dichotomy of AML1-ETO functions: growth arrest versus block of differentiation.
AB  - The fusion gene AML1-ETO is the product of t(8;21)(q22;q22), one of the most
      common chromosomal translocations associated with acute myeloid leukemia. To
      investigate the impact of AML1-ETO on hematopoiesis, tetracycline-inducible AML1
      ETO-expressing cell lines were generated using myeloid cells. AML1-ETO is tightly
      and strongly induced upon tetracycline withdrawal. The proliferation of AML1
      ETO(+) cells was markedly reduced, and most of the cells eventually underwent
      apoptosis. RNase protection assays revealed that the amount of Bcl-2 mRNA was
      decreased after AML1-ETO induction. Enforced expression of Bcl-2 was able to
      significantly delay, but not completely overcome, AML1-ETO-induced apoptosis.
      Prior to the onset of apoptosis, we also studied the ability of AML1-ETO to
      modulate differentiation. AML1-ETO expression altered granulocytic
      differentiation of U937T-A/E cells. More significantly, this change of
      differentiation was associated with the down-regulation of CCAAT/enhancer binding
      protein alpha (C/EBPalpha), a key regulator of granulocytic differentiation.
      These observations suggest a dichotomy in the functions of AML1-ETO: (i)
      reduction of granulocytic differentiation correlated with decreased expression of
      C/EBPalpha and (ii) growth arrest leading to apoptosis with decreased expression
      of CDK4, c-myc, and Bcl-2. We predict that the preleukemic AML1-ETO(+) cells must
      overcome AML1-ETO-induced growth arrest and apoptosis prior to fulfilling their
      leukemogenic potential.

PMID- 11463840
TI  - SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing
      detachment from chromatin early in T-cell apoptosis.
AB  - SATB1 is expressed primarily in thymocytes and orchestrates temporal and spatial
      expression of a large number of genes in the T-cell lineage. SATB1 binds to the
      bases of chromatin loop domains in vivo, recognizing a special DNA context with
      strong base-unpairing propensity. The majority of thymocytes are eliminated by
      apoptosis due to selection processes in the thymus. We investigated the fate of
      SATB1 during thymocyte and T-cell apoptosis. Here we show that SATB1 is
      specifically cleaved by a caspase 6-like protease at amino acid position 254 to
      produce a 65-kDa major fragment containing both a base-unpairing region (BUR)
      binding domain and a homeodomain. We found that this cleavage separates the DNA
      binding domains from amino acids 90 to 204, a region which we show to be a
      dimerization domain. The resulting SATB1 monomer loses its BUR-binding activity,
      despite containing both its DNA-binding domains, and rapidly dissociates from
      chromatin in vivo. We found this dimerization region to have sequence similarity
      to PDZ domains, which have been previously shown to be involved in signaling by
      conferring protein-protein interactions. SATB1 cleavage during Jurkat T-cell
      apoptosis induced by an anti-Fas antibody occurs concomitantly with the high
      molecular-weight fragmentation of chromatin of ~50-kb fragments. Our results
      suggest that mechanisms of nuclear degradation early in apoptotic T cells involve
      efficient removal of SATB1 by disrupting its dimerization and cleavage of genomic
      DNA into loop domains to ensure rapid and efficient disassembly of higher-order
      chromatin structure.

PMID- 11463841
TI  - Increased susceptibility to streptozotocin-induced beta-cell apoptosis and
      delayed autoimmune diabetes in alkylpurine-DNA-N-glycosylase-deficient mice.
AB  - Type 1 diabetes is thought to occur as a result of the loss of insulin-producing
      pancreatic beta cells by an environmentally triggered autoimmune reaction. In
      rodent models of diabetes, streptozotocin (STZ), a genotoxic methylating agent
      that is targeted to the beta cells, is used to trigger the initial cell death.
      High single doses of STZ cause extensive beta-cell necrosis, while multiple low
      doses induce limited apoptosis, which elicits an autoimmune reaction that
      eliminates the remaining cells. We now show that in mice lacking the DNA repair
      enzyme alkylpurine-DNA-N-glycosylase (APNG), beta-cell necrosis was markedly
      attenuated after a single dose of STZ. This is most probably due to the reduction
      in the frequency of base excision repair-induced strand breaks and the consequent
      activation of poly(ADP-ribose) polymerase (PARP), which results in catastrophic
      ATP depletion and cell necrosis. Indeed, PARP activity was not induced in APNG(-/
      ) islet cells following treatment with STZ in vitro. However, 48 h after STZ
      treatment, there was a peak of apoptosis in the beta cells of APNG(-/-) mice.
      Apoptosis was not observed in PARP-inhibited APNG(+/+) mice, suggesting that
      apoptotic pathways are activated in the absence of significant numbers of DNA
      strand breaks. Interestingly, STZ-treated APNG(-/-) mice succumbed to diabetes 8
      months after treatment, in contrast to previous work with PARP inhibitors, where
      a high incidence of beta-cell tumors was observed. In the multiple-low-dose
      model, STZ induced diabetes in both APNG(-/-) and APNG(+/+) mice; however, the
      initial peak of apoptosis was 2.5-fold greater in the APNG(-/-) mice. We conclude
      that APNG substrates are diabetogenic but by different mechanisms according to
      the status of APNG activity.

PMID- 11463842
TI  - Identification and functional characterization of neo-poly(A) polymerase, an RNA
      processing enzyme overexpressed in human tumors.
AB  - Poly(A) polymerase (PAP) plays an essential role in polyadenylation of mRNA
      precursors, and it has long been thought that mammalian cells contain only a
      single PAP gene. We describe here the unexpected existence of a human PAP, which
      we call neo-PAP, encoded by a previously uncharacterized gene. cDNA was isolated
      from a tumor-derived cDNA library encoding an 82.8-kDa protein bearing 71%
      overall similarity to human PAP. Strikingly, the organization of the two PAP
      genes is nearly identical, indicating that they arose from a common ancestor. Neo
      PAP and PAP were indistinguishable in in vitro assays of both specific and
      nonspecific polyadenylation and also endonucleolytic cleavage. Neo-PAP produced
      by transfection was exclusively nuclear, as demonstrated by immunofluorescence
      microscopy. However, notable sequence divergence between the C-terminal domains
      of neo-PAP and PAP suggested that the two enzymes might be differentially
      regulated. While PAP is phosphorylated throughout the cell cycle and
      hyperphosphorylated during M phase, neo-PAP did not show evidence of
      phosphorylation on Western blot analysis, which was unexpected in the context of
      a conserved cyclin recognition motif and multiple potential cyclin-dependent
      kinase (cdk) phosphorylation sites. Intriguingly, Northern blot analysis
      demonstrated that each PAP displayed distinct mRNA splice variants, and both PAP
      mRNAs were significantly overexpressed in human cancer cells compared to
      expression in normal or virally transformed cells. Neo-PAP may therefore be an
      important RNA processing enzyme that is regulated by a mechanism distinct from
      that utilized by PAP.

PMID- 11463843
TI  - Preserved pancreatic beta-cell development and function in mice lacking the
      insulin receptor-related receptor.
AB  - Receptors of the insulin/insulinlike growth factor (IGF) family have been
      implicated in the regulation of pancreatic beta-cell growth and insulin
      secretion. The insulin receptor-related receptor (IRR) is an orphan receptor of
      the insulin receptor gene (Ir) subfamily. It is expressed at considerably higher
      levels in beta cells than either insulin or IGF-1 receptors, and it has been
      shown to engage in heterodimer formation with insulin or IGF-1 receptors. To
      address whether IRR plays a physiologic role in beta-cell development and
      regulation of insulin secretion, we have characterized mice lacking IRR and
      generated a combined knockout of Ir and Irr. We report that islet morphology,
      beta-cell mass, and secretory function are not affected in IRR-deficient mice.
      Moreover, lack of IRR does not impair compensatory beta-cell hyperplasia in
      insulin-resistant Ir(+/-) mice, nor does it affect beta-cell development and
      function in Ir(-/-) mice. We conclude that glucose-stimulated insulin secretion
      and embryonic beta-cell development occur normally in mice lacking Irr.

PMID- 11463844
TI  - Reconstitution of cyclin D1-associated kinase activity drives terminally
      differentiated cells into the cell cycle.
AB  - Terminal cell differentiation entails definitive withdrawal from the cell cycle.
      Although most of the cells of an adult mammal are terminally differentiated, the
      molecular mechanisms preserving the postmitotic state are insufficiently
      understood. Terminally differentiated skeletal muscle cells, or myotubes, are a
      prototypic terminally differentiated system. We previously identified a mid-G(1)
      block preventing myotubes from progressing beyond this point in the cell cycle.
      In this work, we set out to define the molecular basis of such a block. It is
      shown here that overexpression of highly active cyclin E and cdk2 in myotubes
      induces phosphorylation of pRb but cannot reactivate DNA synthesis, underscoring
      the tightness of cell cycle control in postmitotic cells. In contrast, forced
      expression of cyclin D1 and wild-type or dominant-negative cdk4 in myotubes
      restores physiological levels of cdk4 kinase activity, allowing progression
      through the cell cycle. Such reactivation occurs in myotubes derived from
      primary, as well as established, C2C12 myoblasts and is accompanied by impairment
      of muscle-specific gene expression. Other terminally differentiated systems as
      diverse as adipocytes and nerve cells are similarly reactivated. Thus, the
      present results indicate that the suppression of cyclin D1-associated kinase
      activity is of crucial importance for the maintenance of the postmitotic state in
      widely divergent terminally differentiated cell types.

PMID- 11463845
TI  - Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and
      proliferation of endothelial cells.
AB  - The protein kinase Akt is activated by growth factors and promotes cell survival
      and cell cycle progression. Here, we demonstrate that Akt phosphorylates the cell
      cycle inhibitory protein p21(Cip1) at Thr 145 in vitro and in intact cells as
      shown by in vitro kinase assays, site-directed mutagenesis, and phospho-peptide
      analysis. Akt-dependent phosphorylation of p21(Cip1) at Thr 145 prevents the
      complex formation of p21(Cip1) with PCNA, which inhibits DNA replication. In
      addition, phosphorylation of p21(Cip1) at Thr 145 decreases the binding of the
      cyclin-dependent kinases Cdk2 and Cdk4 to p21(Cip1) and attenuates the Cdk2
      inhibitory activity of p21(Cip1). Immunohistochemistry and biochemical
      fractionation reveal that the decrease of PCNA binding and regulation of Cdk
      activity by p21(Cip1) phosphorylation is not caused by altered intracellular
      localization of p21(Cip1). As a functional consequence, phospho-mimetic
      mutagenesis of Thr 145 reverses the cell cycle-inhibitory properties of
      p21(Cip1), whereas the nonphosphorylatable p21(Cip1) T145A construct arrests
      cells in G(0) phase. These data suggest that the modulation of p21(Cip1) cell
      cycle functions by Akt-mediated phosphorylation regulates endothelial cell
      proliferation in response to stimuli that activate Akt.

PMID- 11463846
TI  - Gene targeting reveals a crucial role for MTG8 in the gut.
AB  - The MTG8 (ETO) locus is involved in a reciprocal exchange with runx1 in the
      t(8;21) of acute myeloid leukemia. It is a member of a small gene family encoding
      transcriptional regulators that interact with corepressors and histone
      deacetylase. However, the physiologic cellular processes controlled by MTG8 are
      not known. In order to gain an insight into the latter, we have generated mutant
      mice with an insertional inactivation at the locus, which disrupts transcription
      of exon 2. The postnatal viability of homozygous mutants was greatly reduced. In
      approximately 25% the midgut was missing, whereas practically all pups surviving
      past the first 2 days showed severe growth impairment, which was likely due to a
      gross disruption of the gut architecture. The latter phenotype could be traced
      back to late embryonic development. No difference in gut cell differentiation or
      proliferation was found compared to wild-type littermates. Levels of factors
      known to be involved in gut morphogenesis were also unchanged. MTG8 is expressed
      in the outermost layers of the developing gut from at least E9.5. Thus, MTG8
      plays a novel, essential role in the gastrointestinal system.

PMID- 11463847
TI  - A meiotic chromosomal core consisting of cohesin complex proteins recruits DNA
      recombination proteins and promotes synapsis in the absence of an axial element
      in mammalian meiotic cells.
AB  - The behavior of meiotic chromosomes differs in several respects from that of
      their mitotic counterparts, resulting in the generation of genetically distinct
      haploid cells. This has been attributed in part to a meiosis-specific chromatin
      associated protein structure, the synaptonemal complex. This complex consist of
      two parallel axial elements, each one associated with a pair of sister
      chromatids, and a transverse filament located between the synapsed homologous
      chromosomes. Recently, a different protein structure, the cohesin complex, was
      shown to be associated with meiotic chromosomes and to be required for chromosome
      segregation. To explore the functions of the two different protein structures,
      the synaptonemal complex and the cohesin complex, in mammalian male meiotic
      cells, we have analyzed how absence of the axial element affects early meiotic
      chromosome behavior. We find that the synaptonemal complex protein 3 (SCP3) is a
      main determinant of axial-element assembly and is required for attachment of this
      structure to meiotic chromosomes, whereas SCP2 helps shape the in vivo structure
      of the axial element. We also show that formation of a cohesin-containing
      chromosomal core in meiotic nuclei does not require SCP3 or SCP2. Our results
      also suggest that the cohesin core recruits recombination proteins and promotes
      synapsis between homologous chromosomes in the absence of an axial element. A
      model for early meiotic chromosome pairing and synapsis is proposed.

PMID- 11463848
TI  - The elongation domain of ELL is dispensable but its ELL-associated factor 1
      interaction domain is essential for MLL-ELL-induced leukemogenesis.
AB  - The MLL-ELL chimeric gene is the product of the (11;19)(q23p13.1) translocation
      associated with de novo and therapy-related acute myeloid leukemias (AML). ELL is
      an RNA polymerase II elongation factor that interacts with the recently
      identified EAF1 (ELL associated factor 1) protein. EAF1 contains a limited region
      of homology with the transcriptional activation domains of three other genes
      fused to MLL in leukemias, AF4, LAF4, and AF5q31. Using an in vitro
      transformation assay of retrovirally transduced myeloid progenitors, we conducted
      a structure-function analysis of MLL-ELL. Whereas the elongation domain of ELL
      was dispensable, the EAF1 interaction domain of ELL was critical to the
      immortalizing properties of MLL-ELL in vitro. To confirm these results in vivo,
      we transplanted mice with bone marrow transduced with MLL fused to the minimal
      EAF1 interaction domain of ELL. These mice all developed AML, with a longer
      latency than mice transplanted with the wild-type MLL-ELL fusion. Based on these
      results, we generated a heterologous MLL-EAF1 fusion gene and analyzed its
      transforming potential. Strikingly, we found that MLL-EAF1 immortalized myeloid
      progenitors in the same manner as that of MLL-ELL. Furthermore, transplantation
      of bone marrow transduced with MLL-EAF1 induced AML with a shorter latency than
      mice transplanted with the MLL-ELL fusion. Taken together, these results indicate
      that the leukemic activity of MLL-ELL requires the EAF1 interaction domain of
      ELL, suggesting that the recruitment by MLL of a transactivation domain similar
      to that in EAF1 or the AF4/LAF4/AF5q31 family may be a critical common feature of
      multiple 11q23 translocations. In addition, these studies support a critical role
      for MLL partner genes and their protein-protein interactions in 11q23
      leukemogenesis.

PMID- 11463849
TI  - A murine homologue of the Drosophila brainiac gene shows homology to
      glycosyltransferases and is required for preimplantation development of the
      mouse.
AB  - The neurogenic gene brainiac was first isolated in Drosophila melanogaster, where
      it interacts genetically with members of the Notch signaling cascade. We have
      isolated a murine homologue of the Drosophila brainiac gene and delineated its
      highly specific expression pattern during development and adult life. We find
      particularly strong expression in the developing central nervous system, in the
      developing retina, and in the adult hippocampus. Targeted deletion of mouse
      Brainiac 1 expression leads to embryonic lethality prior to implantation. Null
      embryos can be recovered as blastocysts but do not appear to implant, indicating
      that mouse Brainiac 1, likely a glycosyltransferase, is crucial for very early
      development of the mouse embryo.

PMID- 11463850
TI  - Tracking the role of a star in the sky of the new millennium.
AB  - The steroidogenic acute regulatory protein is indispensable for the biosynthesis
      of steroid hormones. Steroidogenic acute regulatory protein mediates the rate
      limiting step in steroidogenesis, the transfer of cholesterol from the outer
      mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to
      pregnenolone. Its essential role in steroidogenesis was shown when it was
      discovered that mutations in the steroidogenic acute regulatory protein gene in
      humans cause the lipoid form of congenital adrenal hyperplasia, a potentially
      lethal disease resulting from an inability to synthesize steroids. Also, the
      steroidogenic acute regulatory protein null mouse has a phenotype that is
      essentially the same as that observed with human mutations. Studies on the
      regulation of the expression of the steroidogenic acute regulatory protein gene
      has enjoyed considerable progress, yet the complexity of this regulation
      indicates that much work remains. The mechanism whereby steroidogenic acute
      regulatory protein mediates the transfer of cholesterol to the inner
      mitochondrial membrane remains a mystery, but the recent solving of the structure
      of the cholesterol transferring domain of a steroidogenic acute regulatory
      protein homolog coupled with structure-function studies of steroidogenic acute
      regulatory protein in natural and synthetic membranes has allowed for at least
      two models to be proposed. This review will briefly attempt to summarize what is
      currently known about the regulation of the steroidogenic acute regulatory
      protein gene and its mechanism of action, fully understanding that in both areas
      considerable gaps in our knowledge remain.

PMID- 11463851
TI  - Heat shock interferes with steroidogenesis by reducing transcription of the
      steroidogenic acute regulatory protein gene.
AB  - A key regulatory point in fine tuning of steroidogenesis is the synthesis of
      steroidogenic acute regulatory protein, which transfers cholesterol into
      mitochondria. Heat shock and toxic insults reduce steroidogenic acute regulatory
      protein, severely compromising steroid synthesis. As the molecular mechanisms for
      this reduction remain elusive, we tested the hypothesis that heat shock directly
      interferes with transcription of the steroidogenic acute regulatory protein gene.
      We show that, in mouse MA-10 Leydig tumor cells, heat shock caused drastic
      declines in (Bu)(2)cAMP-induced progesterone accumulation and steroidogenic acute
      regulatory protein transcript abundance. A proximal steroidogenic acute
      regulatory protein promoter fragment (-85 to +39) is sufficient to direct both
      cAMP inducibility and heat shock inhibition. Nuclear extracts from MA-10 cells
      displayed binding to this proximal promoter fragment as a low mobility complex in
      gel shift experiments. This complex disappeared in nuclear extracts taken at 5
      and 10 min after initiation of heat shock and reappeared in extracts taken at 2
      and 8 h. Similar low- mobility complexes formed on oligonucleotides representing
      the overlapping subfragments of the minimal steroidogenic acute regulatory
      protein promoter fragment sensitive to the heat shock effect. Extracts from heat
      shocked MA-10 cells displayed reduced complex formation to each of the
      subfragments. We conclude that heat shock reduces progesterone synthesis,
      steroidogenic acute regulatory protein mRNA abundance, and steroidogenic acute
      regulatory protein promoter activity and disrupts binding of nuclear proteins to
      the proximal region of the steroidogenic acute regulatory protein promoter.
      Together these observations provide strong evidence for a mechanism of
      transcriptional inhibition in the down-regulation of steroidogenic acute
      regulatory protein expression by heat shock.

PMID- 11463852
TI  - Salt-inducible kinase is involved in the ACTH/cAMP-dependent protein kinase
      signaling in Y1 mouse adrenocortical tumor cells.
AB  - The involvement of salt-inducible kinase, a recently cloned protein
      serine/threonine kinase, in adrenal steroidogenesis was investigated. When Y1
      mouse adrenocortical tumor cells were stimulated by ACTH, the cellular content of
      salt-inducible kinase mRNA, protein, and enzyme activity changed rapidly. Its
      level reached the highest point in 1-2 h and returned to the initial level after
      8 h. The mRNA levels of cholesterol side-chain cleavage cytochrome P450 and
      steroidogenic acute regulatory protein, on the other hand, began to rise after a
      few hours, reaching the highest levels after 8 h. The salt-inducible kinase mRNA
      level in ACTH-, forskolin-, or 8-bromo-cAMP-treated Kin-7 cells, mutant Y1 with
      less cAMP-dependent PKA activity, remained low. However, Kin-7 cells, when
      transfected with a PKA expression vector, expressed salt-inducible kinase mRNA.
      Y1 cells that overexpressed salt-inducible kinase were isolated, and the mRNA
      levels of steroidogenic genes in these cells were compared with those in the
      parent Y1. The level of cholesterol side-chain cleavage cytochrome P450 mRNA in
      the salt-inducible kinase-overexpressing cells was markedly low compared with
      that in the parent, while the levels of Ad4BP/steroidogenic factor-1-, ACTH
      receptor-, and steroidogenic acute regulatory protein-mRNAs in the former were
      similar to those in the latter. The ACTH-dependent expression of cholesterol side
      chain cleavage cytochrome P450- and steroidogenic acute regulatory protein-mRNAs
      in the salt-inducible kinase-overexpressing cells was significantly repressed.
      The promoter activity of the cholesterol side-chain cleavage cytochrome P450 gene
      was assayed by using Y1 cells transfected with a human cholesterol side-chain
      cleavage cytochrome P450 promoter-linked reporter gene. Addition of forskolin to
      the culture medium enhanced the cholesterol side-chain cleavage cytochrome P450
      promoter activity, but the forskolin-dependently activated promoter activity was
      inhibited when the cells were transfected with a salt-inducible kinase expression
      vector. This inhibition did not occur when the cells were transfected with a salt
      inducible kinase (K56M) vector that encoded an inactive kinase. The salt
      inducible kinase's inhibitory effect was also observed when nonsteroidogenic,
      nonAd4BP/steroidogenic factor-1 -expressing, NIH3T3 cells were used for the
      promoter assays. These results suggested that salt-inducible kinase might play an
      important role(s) in the cAMP-dependent, but Ad4BP/steroidogenic factor-1
      independent, gene expression of cholesterol side-chain cleavage cytochrome P450
      in adrenocortical cells.

PMID- 11463853
TI  - NF-1C, Sp1, and Sp3 are essential for transcription of the human gene for P450c17
      (steroid 17alpha-hydroxylase/17,20 lyase) in human adrenal NCI-H295A cells.
AB  - Cytochrome P450c17 catalyzes steroid 17alpha-hydroxylase and 17,20 lyase
      activities, which are required for the biosynthesis of cortisol and sex steroids.
      Human P450c17 is expressed in a cAMP-responsive, cell-specific, developmentally
      programmed fashion, but little is known about its transcriptional regulation.
      Expression of deletion mutants of up to 2,500 bp of human 5'-flanking DNA in
      human adrenal NCI-H295A cells indicated that most regulatory activity was
      confined to the first 227 bp. Deoxyribonuclease I footprinting of the proximal
      promoter identified the TATA box, an steroidogenic factor-1 site, and three
      previously uncharacterized sites at -107/85, at -178/-152, and at -220/-185.
      EMSAs and methylation interference assays suggested that the -107/-85 site and
      the -178/-152 site bind members of the NF-1 (nuclear factor-1) family of
      transcription factors. An NF-1 consensus sequence generated similar DNA/protein
      complexes, and antibodies against NF-1C2/CTF2 supershifted the complexes formed
      by the -107/-85 site, the -178/-152 site, and the NF-1 consensus site. Western
      blots of nuclear extracts from NCI-H295A cells probed with this NF-1 antiserum
      identified two NF-1 isoforms between 50 and 55 kDa. The presence of NF-1C2 (CTF2)
      and CTF5 in NCI-H295A cells was demonstrated by RT-PCR and sequencing. Mutation
      of both the -107/-85 and the -178/-152 NF-1 sites reduced basal transcription by
      half. Supershift assays showed that the ubiquitous proteins Sp1 and Sp3 both bind
      to the -227/-184 region, and that mutation of their binding sites reduced
      transcription by 75%. Mutation of the Sp1/Sp3 site plus the two NF-1 sites
      eliminated almost all detectable transcription. Thus, Sp1 and Sp3 binding to the 
      227/-184 site and NF-1C proteins binding to the -107/-85 and the -178/-152 sites
      are crucial for adrenal transcription of the human gene for P450c17.

PMID- 11463854
TI  - A free carboxylate oxygen in the side chain of position 674 in transmembrane
      domain 7 is necessary for TSH receptor activation.
AB  - A specific H-bonding network formed between the central regions of transmembrane
      domain 6 and transmembrane domain 7 has been proposed to be critical for
      stabilizing the inactive state of glycoprotein hormone receptors. Many different
      constitutively activating TSH receptor point mutations have been identified in
      hyperfunctioning thyroid adenomas in the lower portion of transmembrane domain 6.
      Position D633 in transmembrane domain 6 of the human TSH receptor is the only one
      in which four different constitutively activating amino acid exchanges have been
      identified. Further in vitro substitutions led to constitutive activation of the
      TSH receptor (D633Y, F, C) as well as to the first inactivating TSH receptor
      mutation in transmembrane domain 6 without changes of membrane expression or TSH
      binding (D633R). Molecular modeling of this inactivating TSH receptor mutation
      revealed potential interaction partners of R633 in transmembrane domain 3 and/or
      transmembrane domain 7, presumably via hydrogen bonds that could be responsible
      for locking the TSH receptor in a completely inactive state. To further elucidate
      the H-bond network that most likely maintains the inactive state of the TSH
      receptor, we investigated these potential interactions by generating TSH receptor
      double mutants designed to break up possible H bonds. We excluded S508 in
      transmembrane domain 3 as a possible interaction partner of R633. In contrast, a
      partial response to TSH stimulation was rescued in a receptor construct with the
      double-substitution D633R/N674D. Our results therefore confirm the H bond between
      position 633 in transmembrane domain 6 and 674 in transmembrane domain 7
      suggested by molecular modeling of the inactivating mutation D633R. Moreover, the
      mutagenesis results, together with a three-dimensional structure model, indicate
      that for TSH receptor activation and G protein-coupled signaling, at least one
      free available carboxylate oxygen is required as a hydrogen acceptor atom at
      position 674 in transmembrane domain 7.

PMID- 11463855
TI  - Regulation of melatonin 1a receptor signaling and trafficking by asparagine-124.
AB  - Melatonin is a pineal hormone that regulates seasonal reproduction and has been
      used to treat circadian rhythm disorders. The melatonin 1a receptor is a seven-
      transmembrane domain receptor that signals predominately via pertussis toxin
      sensitive G-proteins. Point mutations were created at residue N124 in cytoplasmic
      domain II of the receptor and the mutant receptors were expressed in a
      neurohormonal cell line. The acidic N124D- and E-substituted receptors had high
      affinity (125)I-melatonin binding and a subcellular localization similar to the
      neutral N124N wild-type receptor. Melatonin efficacy for the inhibition of cAMP
      by N124D and E mutations was significantly decreased. N124D and E mutations
      strongly compromised melatonin efficacy and potency for inhibition of K(+)
      induced intracellular Ca(++) fluxes and eliminated control of spontaneous calcium
      fluxes. However, these substitutions did not appear to affect activation of Kir3
      potassium channels. The hydrophobic N124L and N124A or basic N124K mutations
      failed to bind (125)I-melatonin and appeared to aggregate or traffic improperly.
      N124A and N124K receptors were retained in the Golgi. Therefore, mutants at N124
      separated into two sets: the first bound (125)I-melatonin with high affinity and
      trafficked normally, but with reduced inhibitory coupling to adenylyl cyclase and
      Ca(++) channels. The second set lacked melatonin binding and exhibited severe
      trafficking defects. In summary, asparagine-124 controls melatonin receptor
      function as evidenced by changes in melatonin binding, control of cAMP levels,
      and regulation of ion channel activity. Asparagine-124 also has a unique
      structural effect controlling receptor distribution within the cell.

PMID- 11463856
TI  - The orphan nuclear receptor TR2 interacts directly with both class I and class II
      histone deacetylases.
AB  - A combination of in vivo and in vitro assays was employed to describe the ligand
      independent interaction of the orphan nuclear receptor TR2 and histone
      deacetylase proteins. The repressive effect of TR2 on transcription of a
      luciferase reporter driven by a promoter containing a direct repeat-5 (DR5)
      derived from the human RARbeta gene was suppressed by the addition of the histone
      deacetylase inhibitor trichostatin A. Immunoprecipitation with FLAG-epitope
      (MDYKDDDDK)-tagged histone deacetylase proteins was used to demonstrate that TR2
      and histone deacetylases 3 or 4 are present in the same immunoprecipitated
      complex. Deacetylase activity was demonstrated for these coimmunoprecipitates,
      further confirming the in vivo interaction of TR2 and histone deacetylases.
      Immunoprecipitation with anti-TR2 antibody was used to demonstrate interaction of
      TR2 with endogenously expressed histone deacetylases 3 and 4 in COS-1 cells.
      Dissection of TR2 domains showed that the DNA binding domain of the receptor was
      responsible for interaction with both histone deacetylases 3 and 4 in glutathione
      S-transferase pull-down assays, while the ligand binding domain did not interact.
      The pull-down data were confirmed with far Western blots that also showed a
      direct interaction between labeled histone deacetylase proteins and TR2. It is
      suggested that repression mediated by unliganded TR2 is mediated, in part, by a
      direct interaction of this receptor with histone deacetylase proteins.

PMID- 11463857
TI  - Human immunodeficiency virus type 1 Tat binding protein-1 is a transcriptional
      coactivator specific for TR.
AB  - The DNA-binding domain of nuclear hormone receptors functions as an interaction
      interface for other transcription factors. Using the DNA-binding domain of
      TRbeta1 as bait in the yeast two-hybrid system, we cloned the Tat binding protein
      1 that was originally isolated as a protein binding to the human immunodeficiency
      virus type 1 Tat transactivator. Tat binding protein-1 has subsequently been
      identified as a member of the ATPase family and a component of the 26S
      proteasome. Tat binding protein-1 interacted with the DNA-binding domain but not
      with the ligand binding domain of TR in vivo and in vitro. TR bound to the amino
      terminal portion of Tat binding protein-1 that contains a leucine zipper-like
      structure. In mammalian cells, Tat binding protein-1 potentiated the ligand
      dependent transactivation by TRbeta1 and TRalpha1 via thyroid hormone response
      elements. Both the intact DNA-binding domain and activation function-2 of the TR
      were required for the transcriptional enhancement in the presence of Tat binding
      protein-1. Tat binding protein-1 did not augment the transactivation function of
      the RAR, RXR, PPARgamma, or ER. The intrinsic activation domain in Tat binding
      protein-1 resided within the carboxyl-terminal conserved ATPase domain, and a
      mutation of a putative ATP binding motif but not a helicase motif in the carboxyl
      terminal conserved ATPase domain abolished the activation function. Tat binding
      protein-1 synergistically activated the TR-mediated transcription with the
      steroid receptor coactivator 1, p120, and cAMP response element-binding protein,
      although Tat binding protein-1 did not directly interact with these coactivators
      in vitro. In contrast, the N-terminal portion of Tat binding protein-1 directly
      interacted in vitro and in vivo with the TR-interacting protein 1 possessing an
      ATPase activity that interacts with the activation function-2 of liganded TR.
      Collectively, Tat binding protein-1 might function as a novel DNA-binding domain
      binding transcriptional coactivator specific for the TR probably in cooperation
      with other activation function-2-interacting cofactors such as TR-interacting
      protein 1.

PMID- 11463858
TI  - Hyperactivation of MAPK induces loss of ERalpha expression in breast cancer
      cells.
AB  - ERalpha-negative breast tumors tend to overexpress growth factor receptors such
      as epidermal growth factor receptor or c-erbB-2. Raf-1 is a key intermediate in
      the signal transduction pathways of these receptors. High levels of constitutive
      Raf kinase (Deltaraf) activity imparts ERalpha- positive MCF-7 breast cancer
      cells with the ability to grow in the absence of estrogen. Deltaraf transfectants
      maintained in estrogen-depleted media showed greatly diminished responses to
      17beta-estradiol or the pure antiestrogen ICI 182,780. Western blotting, ligand
      binding, and immunohistochemistry assays revealed a loss of ERalpha protein
      expression, and ribonuclease protection assays indicated that this correlated
      with loss of ERalpha message. In examining the basal expression of estrogen
      induced genes in the stable transfectants or in transient cotransfection assays
      with an estrogen-response element- reporter construct and Deltaraf or
      constitutively active MAPK kinase (DeltaMEK), no ligand- independent activation
      of ERalpha was observed. Transient expression of Deltaraf and double-label
      immunostaining showed ERalpha was lost in those cells that transiently expressed
      Deltaraf. Abrogation of Raf signaling via treatment with the MEK inhibitors PD
      098059 or U0126 resulted in reexpression of ERalpha. Similar studies performed
      with MCF-7 cells overexpressing epidermal growth factor receptor or c-erbB-2
      confirmed that hyperactivation of MAPK resulted in down-regulation of ERalpha
      that was reversible by MEK inhibition or transfection with dominant negative ERK1
      and ERK2 constructs. These data suggest that the hyperactivation of MAPK in
      epidermal growth factor receptor- or c-erbB-2-overexpressing breast cancer cells
      is directly responsible for generation of an ERalpha-negative phenotype and, more
      importantly, that this process may be abrogated by inhibiting these pathways,
      thus restoring ERalpha expression.

PMID- 11463859
TI  - The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose
      levels in vivo.
AB  - The RXR serves as a heterodimer partner for the PPARgamma and the dimer is a
      molecular target for insulin sensitizers such as the thiazolidinediones. Ligands
      for either receptor can activate PPAR-dependent pathways via PPAR response
      elements. Unlike PPARgamma agonists, however, RXR agonists like LG100268 are
      promiscuous and activate multiple RXR heterodimers. Here, we demonstrate that
      LG100754, a RXR:RXR antagonist and RXR:PPARalpha agonist, also functions as a
      RXR:PPARgamma agonist. It does not activate other LG100268 responsive
      heterodimers like RXR:liver X receptoralpha, RXR:liver X receptorbeta, RXR:bile
      acid receptor/farnesoid X receptor and RXR:nerve growth factor induced gene B.
      This unique RXR ligand triggers cellular RXR:PPARgamma-dependent pathways
      including adipocyte differentiation and inhibition of TNFalpha-mediated
      hypophosphorylation of the insulin receptor, but does not activate key farnesoid
      X receptor and liver X receptor target genes. Also, LG100754 treatment of db/db
      animals leads to an improvement in insulin resistance in vivo. Interestingly,
      activation of RXR:PPARgamma by LG100268 and LG100754 occurs through different
      mechanisms. Therefore, LG100754 represents a novel class of insulin sensitizers
      that functions through RXR but exhibits greater heterodimer selectivity compared
      with LG100268. These results establish an approach to the design of novel RXR
      based insulin sensitizers with greater specificity.

PMID- 11463860
TI  - Inhibitory effects of 1alpha,25-dihydroxyvitamin D(3) on the G(1)-S phase
      controlling machinery.
AB  - The nuclear hormone 1alpha,25-dihydroxyvitamin D(3) induces cell cycle arrest,
      differentiation, or apoptosis depending on target cell type and state. Although
      the antiproliferative effect of 1alpha,25-dihydroxyvitamin D(3) has been known
      for years, the molecular basis of the cell cycle blockade by 1alpha,25
      dihydroxyvitamin D(3) remains largely unknown. Here we have investigated the
      mechanisms underlying the G(1) arrest induced upon 1alpha,25-dihydroxyvitamin
      D(3) treatment of the human breast cancer cell line MCF-7. Twenty-four-hour
      exposure of exponentially growing MCF-7 cells to 1alpha,25-dihydroxyvitamin D(3)
      impeded proliferation by preventing S phase entry, an effect that correlated with
      appearance of the growth-suppressing, hypophosphorylated form of the
      retinoblastoma protein (pRb), and modulation of cyclin-dependent kinase (cdk)
      activities of cdk-4, -6, and -2. Time course immunochemical and biochemical
      analyses of the cellular and molecular effects of 1alpha,25-dihydroxyvitamin D(3)
      treatment for up to 6 d revealed a dynamic chain of events, preventing activation
      of cyclin D1/cdk4, and loss of cyclin D3, which collectively lead to repression
      of the E2F transcription factors and thus negatively affected cyclin A protein
      expression. While the observed 10-fold inhibition of cyclin D1/cdk 4-associated
      kinase activity appeared independent of cdk inhibitors, the activity of cdk 2
      decreased about 20-fold, reflecting joint effects of the lower abundance of its
      cyclin partners and a significant increase of the cdk inhibitor p21(CIP1/WAF1),
      which blocked the remaining cyclin A(E)/cdk 2 complexes. Together with a rapid
      down-modulation of the c-Myc oncoprotein in response to 1alpha,25
      dihydroxyvitamin D(3), these results demonstrate that 1alpha,25-dihydroxyvitamin
      D(3) inhibits cell proliferation by targeting several key regulators governing
      the G(1)/S transition.

PMID- 11463861
TI  - Multiple promoters exist in the human GR gene, one of which is activated by
      glucocorticoids.
AB  - A new human GR gene sequence (hGR 1Ap/e), which is distinct from the previously
      identified human GR promoter and coding sequences, has been isolated and
      characterized. The hGR 1Ap/e sequence is approximately 31 kbp upstream of the
      human GR coding sequence. This sequence (2,056 bp) contains a novel promoter (the
      hGR 1A promoter; 1,075 bp) and untranslated exon sequence (hGR exon 1A sequence;
      981 bp). Alternative splicing produces three different hGR 1A-containing
      transcripts, 1A1, 1A2, and 1A3. GR transcripts containing exon 1A1, 1A2, 1B, and
      1C are expressed at various levels in many cancer cell lines, while the exon 1A3
      containing GR transcript is expressed most abundantly in blood cell cancer cell
      lines. Glucocorticoid hormone treatment causes an up-regulation of exon 1A3
      containing GR transcripts in CEM-C7 T-lymphoblast cells and a down-regulation of
      exon 1A3-containing transcripts in IM-9 B-lymphoma cells. Deoxyribonuclease I
      footprinting using CEM-C7 cell nuclear extract reveals four footprints in the
      promoter region and two intraexonic footprints. Much of the basal promoter
      activating function is found in the +41/+269 sequence, which contains two
      deoxyribonuclease I footprints (FP5 and FP6). When this sequence is cloned into
      the pXP-1 luciferase reporter gene, hormone treatment causes a significant
      increase in luciferase activity in Jurkat T cells that are cotransfected with a
      GR expression vector. FP5 is an interferon regulatory factor-binding element, and
      it contributes significantly to basal transcription rate, but it is not activated
      by steroid. FP6 resembles a glucocorticoid response element and can bind GRbeta.
      This novel hGR 1Ap/e sequence may have future applications for the diagnosis,
      prognosis, and treatment of T-cell leukemia and lymphoma.

PMID- 11463862
TI  - Inhibition of heat shock transcription factor by GR.
AB  - The GR is a hormone-activated transcription factor that acts to regulate specific
      gene expression. In the absence of hormone, the GR and other steroid receptors
      have been shown to form complexes with several mammalian heat shock proteins. As
      heat shock proteins are produced by cells as an adaptive response to stress,
      speculation has existed that communication between the heat shock and
      glucocorticoid hormone signal pathways must exist. Only recently has evidence to
      support this hypothesis been reported. In almost all cases, the evidence has been
      of an ability of heat shock to cause a potentiation of the glucocorticoid hormone
      response. In this proposal, evidence is now presented that heat shock signaling
      can, in turn, be regulated by glucocorticoids. In mouse L929 cells stably
      expressing a chloramphenicol acetyltransferase reporter controlled by the human
      heat shock protein70 promoter and containing known binding sites for heat shock
      transcription factor 1 treatment with glucocorticoid agonist (dexamethasone)
      results in a dose-dependent decrease of stress-induced chloramphenicol
      acetyltransferase gene expression. In these cells, inhibition of heat shock
      protein70 promoter activity by dexamethasone was completely blocked by GR
      antagonist (RU486). Similar treatment of L929 cells stably expressing a
      chloramphenicol acetyltransferase reporter under the control of the
      constitutively active SV40 promoter showed no such inhibition by dexamethasone.
      More importantly, dexamethasone was also found to inhibit heat shock-induced
      expression of the major heat shock proteins-heat shock proteins70, 90, and 110.
      Thus, the inhibitory effect of dexamethasone appears to apply to most, if not
      all, heat shock transcription factor 1-regulated genes. Although dexamethasone
      did not prevent the DNA-binding function of heat shock-activated heat shock
      transcription factor 1, it did inhibit a constitutively active mutant of human
      heat shock transcription factor 1 under nonstress conditions, suggesting that
      dexamethasone repression of heat shock transcription factor 1 was primarily
      through an inhibition of heat shock transcription factor 1 transcription
      enhancement activity. To more accurately characterize the stage of GR signaling
      responsible for inhibition of heat shock transcription factor 1, a series of
      Chinese hamster ovary cells containing either no GR, wild-type mouse GR, or
      single-point mutations of GR were employed. Dexamethasone inhibition of heat
      shock-induced heat shock transcription factor 1 activity was observed in the
      presence of wild-type GR, but not in Chinese hamster ovary cells lacking GR,
      suggesting that signaling cascades other than GR were not involved in this effect
      of dexamethasone. Consistent with this conclusion was the observation that
      dexamethasone had no effect on activity of the MAPKs (ERK1, ERK2, or c-jun N
      terminal kinase), which are known to negatively regulate heat shock transcription
      factor 1. Dexamethasone inhibition of heat shock transcription factor 1 was not
      seen in Chinese hamster ovary cells expressing GR defective for DNA-binding
      function. Moreover, dissociation of GR/Hsp90/Hsp70 complexes was observed in
      response to hormone for both the wild-type and DNA binding-defective forms of GR,
      demonstrating that release of Hsp90 or Hsp70 (both of which are known to keep
      heat shock transcription factor 1 in its inactive state) could be ruled out as a
      potential mechanism. Thus, it appears that GR-mediated transactivation or
      transrepression is required for the inhibitory effect of dexamethasone on heat
      shock transcription factor 1 activity. Taken as a whole, these results provide
      evidence for a novel mechanism of cross-talk in which signaling by the GR can
      attenuate the heat shock response in cells through an inhibition of the
      transcription enhancement activity of HSF1.

PMID- 11463863
TI  - Regulation of phosphoinositide metabolism, Akt phosphorylation, and glucose
      transport by PTEN (phosphatase and tensin homolog deleted on chromosome 10) in
      3T3-L1 adipocytes.
AB  - To investigate the roles of PTEN (phosphatase and tensin homolog deleted on
      chromosome 10) in the regulation of 3-position phosphorylated phosphoinositide
      metabolism as well as insulin-induced Akt phosphorylation and glucose metabolism,
      wild-type PTEN and its phosphatase-dead mutant (C124S) with or without an N
      terminal myristoylation tag were overexpressed in Sf-9 cells and 3T3-L1
      adipocytes using baculovirus and adenovirus systems, respectively. When expressed
      in Sf-9 cells together with the p110alpha catalytic subunit of phosphoinositide 3
      kinase, myristoylated PTEN markedly reduced the accumulations of both
      phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5
      trisphosphate induced by p110alpha. In contrast, overexpression of the C124S
      mutants apparently increased these accumulations. In 3T3-L1 adipocytes, insulin
      induced accumulations of phosphatidylinositol 3,4-bisphosphate and
      phosphatidylinositol 3,4,5-trisphosphate were markedly suppressed by
      overexpression of wild-type PTEN with the N-terminal myristoylation tag, but not
      by that without the tag. On the contrary, the C124S mutants of PTEN enhanced
      insulin-induced accumulations of phosphatidylinositol 3,4-bisphosphate and
      phosphatidylinositol 3,4,5-trisphosphate. Interestingly, the phosphorylation
      level of Akt at Thr308 (Akt2 at Thr309), but not at Ser473 (Akt2 at Ser474), was
      revealed to correlate well with the accumulation of phosphatidylinositol 3,4,5
      trisphosphate modified by overexpression of these PTEN proteins. Finally, insulin
      induced increases in glucose transport activity were significantly inhibited by
      the overexpression of myristoylated wild-type PTEN, but were not enhanced by
      expression of the C124S mutant of PTEN. Therefore, in conclusion, 1) PTEN
      dephosphorylates both phosphatidylinositol 3,4-bisphosphate and
      phosphatidylinositol 3,4,5-trisphosphate in vivo, and the C124S mutants interrupt
      endogenous PTEN activity in a dominant-negative manner. 2) The membrane targeting
      process of PTEN may be important for exerting its function. 3) Phosphorylations
      of Thr309 and Ser474 of Akt2 are regulated differently, and the former is
      regulated very sensitively by the function of PTEN. 4) The phosphorylation level
      of Ser474, but not that of Thr309, in Akt2 correlates well with insulin
      stimulated glucose transport activity in 3T3-L1 adipocytes. 5) The activity of
      endogenous PTEN may not play a major role in the regulation of glucose transport
      activity in 3T3-L1 adipocytes.

PMID- 11463864
TI  - Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate
      insulin secretion.
AB  - In pancreatic beta-cells, voltage-dependent K(+) (Kv) channels are potential
      mediators of repolarization, closure of Ca(2+) channels, and limitation of
      insulin secretion. The specific Kv channels expressed in beta-cells and their
      contribution to the delayed rectifier current and regulation of insulin secretion
      in these cells are unclear. High-level protein expression and mRNA transcripts
      for Kv1.4, 1.6, and 2.1 were detected in rat islets and insulinoma cells.
      Inhibition of these channels with tetraethylammonium decreased I(DR) by
      approximately 85% and enhanced glucose-stimulated insulin secretion by 2- to 4
      fold. Adenovirus-mediated expression of a C-terminal truncated Kv2.1 subunit,
      specifically eliminating Kv2 family currents, reduced delayed rectifier currents
      in these cells by 60-70% and enhanced glucose-stimulated insulin secretion from
      rat islets by 60%. Expression of a C-terminal truncated Kv1.4 subunit, abolishing
      Kv1 channel family currents, reduced delayed rectifier currents by approximately
      25% and enhanced glucose-stimulated insulin secretion from rat islets by 40%.
      This study establishes that Kv2 and 1 channel homologs mediate the majority of
      repolarizing delayed rectifier current in rat beta-cells and that antagonism of
      Kv2.1 may prove to be a novel glucose-dependent therapeutic treatment for type 2
      diabetes.

PMID- 11463867
TI  - Decreased carotid artery distensibility as a sign of early atherosclerosis in
      viscose rayon workers.
AB  - Carbon disulphide (CS(2)) is known to accelerate atherosclerosis and to increase
      the risk for cardiovascular diseases. To assess the effect of CS(2) on the
      functional (distensibility and compliance) and the structural (intima media
      thickness) properties of the common carotid artery, and blood pressure and lipid
      metabolism parameters, a cross-sectional study on 85 workers from a viscose rayon
      factory and 37 controls was carried out. Exposure to CS(2) was assessed by
      personal monitoring and was well below the threshold limit value-time weighted
      average. Carotid arterial wall properties were determined using a non-invasive
      ultrasound wall movement detector system. No significant effect of CS(2) on blood
      pressure, total cholesterol, high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol or triglycerides was found. Among the vascular parameters
      studied, only distensibility was significantly lower and heart rate was
      significantly higher in exposed subjects compared with the controls. In
      conclusion, occupational exposure to CS(2) may cause early alterations in
      arterial elastic properties in young individuals, and even before lipid and
      clinical findings have occurred, important functional changes in the vessel wall
      are present.

PMID- 11463868
TI  - A review of studies on maternal occupational exposures and birth defects, and the
      limitations associated with these studies.
AB  - The proportion of pregnant women who work during pregnancy is increasing as more
      women move into previously male-dominated occupations. With this move,
      occupational exposure to chemical or physical factors during pregnancy could be
      further increased. In the last decade, there have been many reports on the causes
      of birth defects. Unfortunately, most reported associations between occupational
      exposures and adverse reproductive outcomes in epidemiological studies are
      equivocal and often controversial. Many reported associations are only
      suggestive. More information is needed before firm conclusions can be drawn. The
      major reasons for ambiguous findings are due to limitations of study methodology,
      e.g. inappropriate endpoints, multiple confounders, low study power and
      inadequate analysis methods. It must also be noted that maternal work, and
      therefore exposure, may also differ greatly from country to country.

PMID- 11463869
TI  - High-frequency (10-18 kHz) hearing thresholds: reliability, and effects of age
      and occupational noise exposure.
AB  - The objective was to investigate the reliability and effects of age and noise on
      high-frequency hearing thresholds. A cross-sectional study was used involving 187
      exposed and 52 non-industrial noise-exposed subjects selected randomly from noise
      exposed and non-industrial noise-exposed subjects, respectively. Each subject was
      tested with both conventional-frequency (0.25-8 kHz) and high-frequency (10-18
      kHz) audiometry. Test-retest results showed that high-frequency audiometry (HFA)
      was as reliable as the conventional procedure. Although the inter-subject
      variation was large, the intra-subject variation was small, indicating that HFA
      can be used more reliably than the conventional procedure to monitor individual
      cases over time. Both the hearing threshold at high frequencies and the upper
      frequency limit deteriorated as a function of age and frequency. The exposed
      subjects had significantly higher hearing thresholds than the non-exposed
      subjects at all the high frequencies tested, the difference between the two
      groups being greatest at 14 kHz. Multivariate analysis indicated that age was the
      primary predictor and noise exposure the secondary predictor of hearing
      thresholds in a high frequency range (10-18 kHz). In contrast, multivariate
      analysis indicated the reverse order-noise exposure as the primary predictor,
      then age-for a conventional frequency range (0.25-8 kHz). The results of this
      study suggest that HFA might be used as an early indicator for noise-induced
      hearing loss and acoustic trauma rather than audiometry at a conventional
      frequency (4 kHz), particularly for younger groups.

PMID- 11463870
TI  - Respiratory disorders and allergies in tea packers.
AB  - The aim of this study was to determine whether respiratory symptoms or cross
      shift declines in lung function were related to occupational exposure to tea
      dust. A cross-sectional epidemiological study was conducted at a tea-packing
      plant. Subjects completed a questionnaire, spirometry before and after a full
      work shift, skin prick testing and venipuncture. Among the 83% of the workers at
      the site who participated, the prevalences of asthma, wheezing, hay fever and
      atopy were similar to the general population. Work-related nasal symptoms were
      more commonly reported by blenders and operators. There were six (3.2%) subjects
      with a cross-shift decline in the forced expiratory volume in 1 s of > 10%.
      Specific immunoglobulin E antibodies to black or chamomile tea were observed in
      10 (5.6%) employees. As there was little evidence of specific allergic
      sensitization to the tea varieties tested, the excess of work-related respiratory
      and nasal symptoms probably represented non-specific irritation.

PMID- 11463871
TI  - The calculation of accident risks in fitness for work assessments: diseases that
      can cause sudden incapacity.
AB  - Risk equations have been developed to assist in determining fitness for work of
      people with diseases that may cause rapid loss of control. The four equations
      calculate the frequency of fatal injury to the person with the disease, the
      frequency of fatal injury to colleagues in the workplace, and the cost of fatal
      injury and property damage to the employer. It is suggested that the additional
      risk of fatal injury to the person with the disease should not exceed the fatal
      injury rate in high-risk industries such as forestry, fishing and mining. It is
      also suggested that the additional risk of fatal injury to each colleague should
      be no more than one-tenth of the fatal injury rate due to motor vehicle accidents
      in the community. Two hypothetical case examples are given, demonstrating the use
      of the equations. The equations highlight the need to examine the risks
      associated with individuals, their specific jobs and their workplaces. They also
      highlight significant uncertainties in the determination of fitness, which
      perhaps have been underestimated in the past. Wherever possible, redundant
      defences should be utilized to prevent accidents in the event of sudden
      incapacity.

PMID- 11463872
TI  - A comparison between two methods of aesthesiometric assessment in patients with
      hand-arm vibration syndrome.
AB  - Hand-arm vibration syndrome (HAVS) is caused by prolonged exposure to vibration.
      The diagnosis and assessment of disease severity are subjective at present. The
      aim of this study was to determine sensorineural dysfunction in patients with
      HAVS using two methods of aesthesiometric assessment. We recruited three groups
      of age-matched subjects: 20 subjects diagnosed as having HAVS, 15 manual workers
      and 15 sedentary workers. We measured both two-point discrimination and depth
      sense perception using an aesthesiometer. We found that the two-point
      discrimination wheel was more accurate than the depth sense perception wheel at
      detecting levels of sensorineural dysfunction in subjects with HAVS. The
      increased sensitivity of the two-point disc would suggest that it should be used
      in preference to the depth sense disc for the assessment of sensorineural
      dysfunction in patients with HAVS.

PMID- 11463873
TI  - Multidisciplinary team evaluation of upper extremity injuries in a single visit:
      the UPPER Program.
AB  - Musculoskeletal disorders are the leading cause of disability among people
      between 18 and 64 years of age. Patients with musculoskeletal injuries of the
      upper extremities are usually evaluated and treated by an individual physician
      and therapist. However, for patients who have problems, especially after being
      treated by a hand surgeon and a certified hand therapist, there are few other
      management options. A multidisciplinary assessment program for patients with
      chronic upper limb pain has not been described in the literature. As part of The
      University of Michigan RERC (Rehabilitation Engineering Research Center), the
      UPPER Program (UPper extremity Protocol Evaluation in Rehabilitation) was
      developed to evaluate patients who have disabling upper limb musculoskeletal
      disorders. At the center of the program is a multidisciplinary team composed of a
      physiatrist (physical medicine and rehabilitation specialist), occupational
      therapist, physical therapist, exercise physiologist, vocational counselor and
      pain psychologist. The UPPER Program elements include a pre-evaluation
      questionnaire, individual team member assessments and a team meeting. It is
      followed by a patient appointment with the team physician to review the results
      and recommendations. The essential details of the program are presented in this
      article so it can be reproduced elsewhere.

PMID- 11463874
TI  - The Life Events Inventory: re-scaling based on an occupational sample.
AB  - The objective of this study was to compare the validity of the original
      weightings used by the Life Events Inventory (LEI) with those obtained from a
      contemporary occupational sample. Fifty male and 62 female manufacturing
      employees (age range 16-55 years) assigned scores to each item on a slightly
      modified version of the LEI scale. The current sample consistently assigned
      higher weights to events/items than did the original sample, but there was high
      agreement in terms of item ranking. Some distinct age and gender differences in
      scoring were apparent, and are discussed further. It was concluded that when
      separate weightings are employed for age and gender groups, the LEI remains a
      useful tool for quantifying background levels of stress in both workplace stress
      audits and epidemiological studies where statistical control for non-occupational
      sources of stress is required.

PMID- 11463875
TI  - Hypocalcaemia and hypomagnesaemia due to hydrofluoric acid.
AB  - Hydrofluoric acid readily penetrates the skin and mucous membranes, causing deep
      tissue layer destruction. Dermal exposure can produce hypocalcaemia,
      hypomagnesaemia, hyperkalaemia, cardiac dysrhythmias and death. We report the
      case of a 52-year-old man who presented hypocalcaemia and hypomagnesaemia due to
      occupational dermal contact with hydrofluoric acid. Hypocalcaemia and
      hypomagnesaemia were corrected by i.v. administration of calcium gluconate and
      magnesium sulphate.

PMID- 11463876
TI  - Re: The assessment of fitness to travel.

PMID- 11463877
TI  - Public health. Responding to market failures in tuberculosis control.

PMID- 11463878
TI  - Regulation of transcriptional activation domain function by ubiquitin.
AB  - The ability of transcriptional activation domains (TADs) to signal ubiquitin
      mediated proteolysis suggests an involvement of the ubiquitin-proteasome pathway
      in transcription. To probe this involvement, we asked how ubiquitylation
      regulates the activity of a transcription factor containing the VP16 TAD. We show
      that the VP16 TAD signals ubiquitylation through the Met30 ubiquitin-ligase and
      that Met30 is also required for the VP16 TAD to activate transcription. The
      requirement for Met30 in transcription is circumvented by fusion of ubiquitin to
      the VP16 activator, demonstrating that activator ubiquitylation is essential for
      transcriptional activation. We propose that ubiquitylation regulates TAD function
      by serving as a dual signal for activation and activator destruction.

PMID- 11463880
TI  - The Smithsonian affair.

PMID- 11463879
TI  - No supermassive black hole in M33?
AB  - We observed the nucleus of M33, the third-brightest galaxy in the Local Group,
      with the Space Telescope Imaging Spectrograph at a resolution at least a factor
      of 10 higher than previously obtained. Rather than the steep rise expected within
      the radius of gravitational influence of a supermassive black hole, the random
      stellar velocities showed a decrease within a parsec of the center of the galaxy.
      The implied upper limit on the mass of the central black hole is only 3000 solar
      masses, about three orders of magnitude lower than the dynamically inferred mass
      of any other supermassive black hole. Detecting black holes of only a few
      thousand solar masses is observationally challenging, but it is critical to
      establish how supermassive black holes relate to their host galaxies, and which
      mechanisms influence the formation and evolution of both.

PMID- 11463882
TI  - Astronomy. Nearby galaxy breaks the black hole chain.

PMID- 11463881
TI  - Biomedical research. Pentagon proposes to cut AIDS research from defense budget.

PMID- 11463883
TI  - Clinical research. Procedures faulted in fatal asthma trial.

PMID- 11463884
TI  - Astronomy. Wet stellar system like ours found.

PMID- 11463885
TI  - Space station science. Congress orders halt to planned NASA cuts.

PMID- 11463886
TI  - Smithsonian Institution. New panel will redirect science.

PMID- 11463887
TI  - Genomics. Animals line up to be sequenced.

PMID- 11463888
TI  - Microbiology. S. pneumoniae genome falls to sequencers.

PMID- 11463889
TI  - Japan. Lab chiefs decry push for strategic research.

PMID- 11463890
TI  - Intellectual property. Appeals court clears way for academic suits.

PMID- 11463891
TI  - Stem cell research. NIH review outlines 'enormous promise'.

PMID- 11463892
TI  - Yugoslavia. Science goes begging in recovery package.

PMID- 11463893
TI  - Treaty compliance. Down to the wire on bioweapons talks.

PMID- 11463894
TI  - Infectious diseases. Malaria's beginnings: on the heels of hoes?

PMID- 11463895
TI  - Biogeochemistry. 'Inconceivable' bugs eat methane on the ocean floor.

PMID- 11463896
TI  - Profile. A man and his archive seek greener pastures.

PMID- 11463897
TI  - Climate change. Uncertainty and climate change assessments.
AB  - Clear and quantitative discussion of uncertainties is critical for public policy
      making on climate change. The recently completed report of the Intergovernmental
      Panel on Climate Change assessed the uncertainty in its findings and forecasts.
      The uncertainty assessment process of the IPCC should be improved in the future
      by using a consistent approach to quantifying uncertainty, focusing the
      quantification on the few key results most important for policy making. The
      uncertainty quantification procedure should be fully documented, and if expert
      judgment is used, a specific list of the experts consulted should be included.

PMID- 11463898
TI  - Climate change. Uncertainty in the IPCC's Third Assessment Report.

PMID- 11463899
TI  - Evolution. The Cambrian explosion exploded?

PMID- 11463900
TI  - Weather. Hurricane threats.

PMID- 11463901
TI  - Malaria. Protecting against bad air.

PMID- 11463902
TI  - Neuroscience. The meaning of a mini.

PMID- 11463903
TI  - Electron transfer. Sometimes you can go home again.

PMID- 11463904
TI  - Biomedicine. Huntingtin--profit and loss.

PMID- 11463905
TI  - Polymer dynamics. Chance encounters.

PMID- 11463906
TI  - Interpretation of high projections for global-mean warming.
AB  - The Intergovernmental Panel on Climate Change (IPCC) has recently released its
      Third Assessment Report (TAR), in which new projections are given for global-mean
      warming in the absence of policies to limit climate change. The full warming
      range over 1990 to 2100, 1.4 degrees to 5.8 degrees C, is substantially higher
      than the range given previously in the IPCC Second Assessment Report. Here we
      interpret the new warming range in probabilistic terms, accounting for
      uncertainties in emissions, the climate sensitivity, the carbon cycle, ocean
      mixing, and aerosol forcing. We show that the probabilities of warming values at
      both the high and low ends of the TAR range are very low. In the absence of
      climate-mitigation policies, the 90% probability interval for 1990 to 2100
      warming is 1.7 degrees to 4.9 degrees C.

PMID- 11463907
TI  - Optical control of electrons during electron transfer.
AB  - The dynamics of electron transfer reactions in solution can be controlled with
      the use of a sequence of femtosecond laser pulses. In the charge transfer to
      solvent (CTTS) reaction of sodide (Na-) in tetrahydrofuran, an initial light
      pulse launched the CTTS reaction, ejecting an electron into either an immediate
      or a solvent-separated Na0:solvated electron contact pair. A second pulse was
      used to excite the electrons in the contact pairs, and a third pulse monitored
      the amount of Na- produced through the back electron transfer. Excitation of the
      electrons in immediate contact pairs shut off the back electron transfer, whereas
      excitation of the electrons in solvent-separated pairs both enhanced and hindered
      the back electron transfer.

PMID- 11463908
TI  - Impact of polymer tether length on multiple ligand-receptor bond formation.
AB  - The promoters of cell adhesion are ligands, which are often attached to flexible
      tethers that bind to surface receptors on adjacent cells. Using a combination of
      Monte Carlo simulations, diffusion reaction theory, and direct experiments
      (surface force measurements) of the biotin-streptavidin system, we have
      quantified polymer chain dynamics and the kinetics and spatial range of tethered
      ligand-receptor binding. The results show that the efficiency of strong binding
      does not depend solely on the molecular architecture or binding energy of the
      receptor-ligand pair, nor on the equilibrium configuration of the polymer tether,
      but rather on its "rare" extended conformations.

PMID- 11463909
TI  - Physical structure and inversion charge at a semiconductor interface with a
      crystalline oxide.
AB  - We show that the physical and electrical structure and hence the inversion charge
      for crystalline oxides on semiconductors can be understood and systematically
      manipulated at the atomic level. Heterojunction band offset and alignment are
      adjusted by atomic-level structural and chemical changes, resulting in the
      demonstration of an electrical interface between a polar oxide and a
      semiconductor free of interface charge. In a broader sense, we take the metal
      oxide semiconductor device to a new and prominent position in the solid-state
      electronics timeline. It can now be extensively developed using an entirely new
      physical system: the crystalline oxides-on-semiconductors interface.

PMID- 11463910
TI  - Remotely sensed biological production in the equatorial Pacific.
AB  - A combination of ship, buoy, and satellite observations in the tropical Pacific
      during the period from 1992 to 2000 provides a basin-scale perspective on the net
      effects of El Nino and La Nina on biogeochemical cycles. New biological
      production during the 1997-99 El Nino/La Nina period varied by more than a factor
      of 2. The resulting interannual changes in global carbon sequestration associated
      with the El Nino/La Nina cycle contributed to the largest known natural
      perturbation of the global carbon cycle over these time scales.

PMID- 11463911
TI  - The recent increase in Atlantic hurricane activity: causes and implications.
AB  - The years 1995 to 2000 experienced the highest level of North Atlantic hurricane
      activity in the reliable record. Compared with the generally low activity of the
      previous 24 years (1971 to 1994), the past 6 years have seen a doubling of
      overall activity for the whole basin, a 2.5-fold increase in major hurricanes
      (>/=50 meters per second), and a fivefold increase in hurricanes affecting the
      Caribbean. The greater activity results from simultaneous increases in North
      Atlantic sea-surface temperatures and decreases in vertical wind shear. Because
      these changes exhibit a multidecadal time scale, the present high level of
      hurricane activity is likely to persist for an additional approximately 10 to 40
      years. The shift in climate calls for a reevaluation of preparedness and
      mitigation strategies.

PMID- 11463912
TI  - A phosphatocopid crustacean with appendages from the Lower Cambrian.
AB  - Here we describe a phosphatocopid arthropod with preserved soft anatomy from
      Lower Cambrian rocks of Shropshire, England, which provides evidence for the
      occurrence of Crustacea, including Eucrustacea, in the Early Cambrian. The find
      identifies an important, stratigraphically early source of well-preserved fossils
      (Konservat-Lagerstatte).

PMID- 11463913
TI  - Recent origin of Plasmodium falciparum from a single progenitor.
AB  - Genetic variability of Plasmodium falciparum underlies its transmission success
      and thwarts efforts to control disease caused by this parasite. Genetic variation
      in antigenic, drug resistance, and pathogenesis determinants is abundant,
      consistent with an ancient origin of P. falciparum, whereas DNA variation at
      silent (synonymous) sites in coding sequences appears virtually absent,
      consistent with a recent origin of the parasite. To resolve this paradox, we
      analyzed introns and demonstrated that these are deficient in single-nucleotide
      polymorphisms, as are synonymous sites in coding regions. These data establish
      the recent origin of P. falciparum and further provide an explanation for the
      abundant diversity observed in antigen and other selected genes.

PMID- 11463914
TI  - Methane-consuming archaea revealed by directly coupled isotopic and phylogenetic
      analysis.
AB  - Microorganisms living in anoxic marine sediments consume more than 80% of the
      methane produced in the world's oceans. In addition to single-species aggregates,
      consortia of metabolically interdependent bacteria and archaea are found in
      methane-rich sediments. A combination of fluorescence in situ hybridization and
      secondary ion mass spectrometry shows that cells belonging to one specific
      archaeal group associated with the Methanosarcinales were all highly depleted in
      13C (to values of -96 per thousand). This depletion indicates assimilation of
      isotopically light methane into specific archaeal cells. Additional microbial
      species apparently use other carbon sources, as indicated by significantly higher
      13C/12C ratios in their cell carbon. Our results demonstrate the feasibility of
      simultaneous determination of the identity and the metabolic activity of
      naturally occurring microorganisms.

PMID- 11463915
TI  - Persistence of native-like topology in a denatured protein in 8 M urea.
AB  - Experimental methods have demonstrated that when a protein unfolds, not all of
      its structure is lost. Here we report measurement of residual dipolar couplings
      in denatured forms of the small protein staphylococcal nuclease oriented in
      strained polyacrylamide gels. A highly significant correlation among the dipolar
      couplings for individual residues suggests that a native-like spatial positioning
      and orientation of chain segments (topology) persists to concentrations of at
      least 8 molar urea. These data demonstrate that long-range ordering can occur
      well before a folding protein attains a compact conformation, a conclusion not
      anticipated by any of the standard models of protein folding.

PMID- 11463916
TI  - Complete genome sequence of a virulent isolate of Streptococcus pneumoniae.
AB  - The 2,160,837-base pair genome sequence of an isolate of Streptococcus
      pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia,
      meningitis, and otitis media, contains 2236 predicted coding regions; of these,
      1440 (64%) were assigned a biological role. Approximately 5% of the genome is
      composed of insertion sequences that may contribute to genome rearrangements
      through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of
      polysaccharides and hexosamines provide a substantial source of carbon and
      nitrogen for S. pneumoniae and also damage host tissues and facilitate
      colonization. A motif identified within the signal peptide of proteins is
      potentially involved in targeting these proteins to the cell surface of low
      guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins
      that may serve as potential vaccine candidates were identified. Comparative
      genome hybridization with DNA arrays revealed strain differences in S. pneumoniae
      that could contribute to differences in virulence and antigenicity.

PMID- 11463917
TI  - Absence of junctional glutamate receptor clusters in Drosophila mutants lacking
      spontaneous transmitter release.
AB  - Little is known about the functional significance of spontaneous miniature
      synaptic potentials, which are the result of vesicular exocytosis at nerve
      terminals. Here, by using Drosophila mutants with specific defects in presynaptic
      function, we found that glutamate receptors clustered normally at neuromuscular
      junctions of mutants that retained spontaneous transmitter secretion but had lost
      the ability to release transmitter in response to action potentials. In contrast,
      receptor clustering was defective in mutants in which both spontaneous and evoked
      vesicle exocytosis were absent. Thus, spontaneous vesicle exocytosis appears to
      be tightly linked to the clustering of glutamate receptors during development.

PMID- 11463918
TI  - Tech.Sight. Industrializing structural biology.

PMID- 11463919
TI  - The role of Mycoplasma genitalium in non-gonococcal urethritis.

PMID- 11463920
TI  - Sorting out the new HSV type specific antibody tests.
AB  - This review will delineate performance characteristics and limitations, as far as
      they are known, of the new glycoprotein G based, type specific HSV serologies.
      Several of these tests have been FDA approved in the United States for use in
      adults. With the departure of Gull/Meridian from the HSV serology market, it is
      important for clinicians to understand the sources and claims of the remaining
      type specific tests. Moreover, inaccurate tests using crude antigen preparations
      remain on the market. These tests are identified based on product insert
      information provided by company representatives.

PMID- 11463921
TI  - Surveys on sexual health: recent developments and future directions.
AB  - The increasingly widespread adoption of the term sexual health reflects a move
      away from the medicalisation of this specialty. The focus has shifted from
      clinical practice to lifestyle and behaviour; from clinician to client, and from
      treatment to prevention. This article discusses these themes, identifying their
      implications for sexual health research. Recent times have seen, for example, a
      growing number of studies combining biological and behavioural measures conducted
      by interdisciplinary teams able to combine biomedical measurements of morbidity
      with insights into the subjective interpretations of symptoms and consequences.
      Considerable progress has been made, too, in mounting community based studies,
      and much has been achieved in gaining compliance and refining sampling methods.
      Integrated sexual health services, encompassing more than contraceptive or
      prophylactic service provision, have provided the impetus to investigation of the
      costs and benefits of coordinated family planning and genitourinary medicine
      services. Despite its broader focus, there remain opportunities for sexual health
      research to expand its remit. Studies to date may have focused too narrowly on
      pathological, to the neglect of health enhancing, consequences of sexual
      behaviour.

PMID- 11463922
TI  - Assessing the impact of national anti-HIV sexual health campaigns: trends in the
      transmission of HIV and other sexually transmitted infections in England.
AB  - OBJECTIVE: To assess the impact of the sexual component of AIDS and HIV campaigns
      on transmission of HIV and other sexually transmitted infections (STIs). DESIGN:
      Comparison of time series data. SETTING: England, 1971-1999. OUTCOME MEASURES:
      HIV transmission and diagnoses among men who have sex with men (MSMs), rates of
      attendances and specific STI diagnoses (per 100 000 total population) at
      genitourinary medicine (GUM) clinics. RESULTS: Awareness of AIDS and campaigns in
      1983-4 among homosexual men coincided with substantial declines in transmission
      of HIV and diagnoses of syphilis among MSMs. During general population campaigns
      in 1986-7 new GUM clinic attendances requiring treatment fell by 117/10(5) in men
      and 42/10(5) in women. Rates for gonorrhoea fell by 81/10(5) and 43/10(5) and
      genital herpes by 6/10(5) and 4/10(5), respectively. Previous rises in genital
      wart rates were interrupted, while rates of attendances not requiring treatment
      (the "worried well") increased by 47/10(5) and 58/10(5) for men and women,
      respectively. Since 1987 diagnoses of HIV among MSMs have not declined, averaging
      1300-1400 annually. Following a period of unchanging rates there have been
      substantial increases in GUM attendances requiring treatment, notably for
      gonorrhoea, syphilis, and viral STIs since 1995. CONCLUSIONS: Self help
      initiatives and awareness among homosexual men in 1983-4 contributed
      significantly to a fall in HIV transmission among MSMs, and the general campaigns
      of 1986-7 were associated with similar effects on all STI transmission. Both
      effects seem to have occurred through changing sexual behaviour, and probably
      contributed to the UK's low national HIV prevalence. Bacterial STI incidence has
      increased significantly since 1995 and there is no evidence that recent
      prevention initiatives have reduced HIV transmission among MSMs, hence sexual
      health initiatives need to be comprehensively reinvigorated in England.

PMID- 11463924
TI  - Sexual behaviour among youths at high risk for HIV-1 infection in Dar es Salaam,
      Tanzania.
AB  - OBJECTIVES: To investigate sex specific sexual behaviour in youths visiting a
      youth clinic for sexual and reproductive health in Dar es Saalam. METHODS: A
      questionnaire was administered to a random sample of youths between 10 and 24
      years of age attending the youth health clinic in Dar es Saalam. The clinical
      investigation included testing for syphilis and HIV-1 antibodies RESULTS: 1423
      youths attended the clinic between September 1997 and August 1998. The study
      population comprised 213 (53.5%) males and 185 (46.5%) females. 97 (24.4%) were
      below 20 years. The mean age at coitarche was 16.5 and 17.0 years of age for
      males and females, respectively. The coitarche was involuntary in 15 females
      (8.6%). 49.5% males reported more than five lifetime partners compared with 14.1%
      for females (p<0.0001). Males reported recent partners to be 2.5 years younger,
      while females reported them to be 5.0 years older. No contraceptive use was
      reported by 29.7% of the males and 40.3% of females. 52.7% females had been
      pregnant and 26 (14.1%) reported induced abortions. Genital discharge was found
      in 69.5% and 73.9% and GUD in 36.6% and 27.1% of males and females respectively.
      12 males (5.9%) and 43 females (24.6%) were found to be HIV-1 infected. 13.8% of
      the females with only one lifetime partner were HIV-1 infected compared with
      40.9% with more than five partners (p = 0.028). CONCLUSIONS: Many youths in Dar
      es Salaam engage in sexual behaviours that put them at risk of unwanted
      pregnancies and STIs including HIV infection. Female youths were more likely to
      contract HIV infection than males. In African urban areas youth oriented clinics
      can have a pivotal role in HIV/STI prevention and control

PMID- 11463923
TI  - The interrelation of HIV, cervical human papillomavirus, and neoplasia among
      antenatal clinic attenders in Tanzania.
AB  - OBJECTIVES: To determine the prevalence and interrelation of cervical human
      papillomavirus (HPV) genotypes, squamous intraepithelial lesions (SIL), HIV, and
      other reproductive tract infections (RTIs) among urban antenatal clinic attenders
      in Mwanza, Tanzania. METHODS: Genital swabs were collected from 660 pregnant
      women and tested for a range of RTIs and for cervical cytology. Cervical HPV-DNA
      was detected by PCR and genotyped. HIV and syphilis serologies were performed.
      RESULTS: HPV prevalence was 34% (209/612 women). Of the 144 typeable samples, 83%
      were high risk (HR-HPV) oncogenic strains (56% HPV 16 related types). SIL was
      detected in 43 women (7%), with high grade SIL in 3%. There was a high prevalence
      of HIV (15%), and of any RTI (83%). Genital warts were detected in 20 women (3%).
      HPV infection was associated with some behavioural factors (short duration of
      relationship, single status, not using condoms) and gonorrhoea. There was no
      overall association between HPV and HIV (OR=1.02, 95% CI 0.6-1.6), but a non
      significant trend towards a stronger association with HR-HPV in women aged 15-19
      (OR=2.79, 95% CI 0.8-9.5) and women aged > or =30 (OR=3.20, 95% CI 0.7-15). SIL
      was associated with HPV (OR=3.66, 95% CI 1.9-7.0), but not significantly with HIV
      (OR=1.54, 95% CI 0.7-3.4). Prevalence of SIL was higher among women dually
      positive for HPV/HIV compared to HPV infection only (21% v 12%), although this
      difference was not statistically significant (p=0.17). CONCLUSIONS: HPV infection
      was highly prevalent in this young antenatal population. The association of HIV
      with HR-HPV types in older women may suggest that the principal HIV/HPV
      interaction in this population is for HIV to upregulate HPV persistence, leading
      to subsequent development of SIL.

PMID- 11463925
TI  - Diagnosis of human papillomavirus infection by dry vaginal swabs in military
      women.
AB  - OBJECTIVE: Human papillomavirus (HPV) assays are likely to be used with
      increasing frequency in clinical management of women with abnormal Papanicolaou
      smears and in cervical cancer screening. Our objective was to simplify the method
      of collection of female genital tract specimens. The utility of vaginal dry swabs
      for HPV diagnosis was evaluated. METHODS: Specimens for cytology and for HPV
      identification were collected by a clinician from 189 female soldiers attending a
      military clinic. Three methods of specimen collection for HPV identification were
      compared: a vaginal dry swab (v-DRY), and vaginal and cervical swabs placed into
      specimen transport medium (v-STM and c-STM). Swabs were shipped to a STD
      laboratory for processing. Specific HPV types were identified by a consensus
      primer based PCR based method. Results from 165 women were evaluable. RESULTS:
      HPV prevalence by the three methods was similar and ranged from 44.8% to 50.9%.
      53 (32.1%) women were HPV positive and 60 (36.4%) women were HPV negative by all
      three collection methods. With respect to the risk categories of specific HPV
      types, there was greater agreement between the results from the two vaginal (v
      DRY and v-STM) samples (kappa values of 0.69-0.81) than between the cervical (c
      STM) and either of the vaginal samples (kappa values of 0.37-0.55). The HPV yield
      from c-STM was somewhat greater than that from the vaginal specimens but the
      correlation between cytological abnormalities and HPV was high for all three
      methods. CONCLUSION: A dry vaginal swab may be an acceptable method of specimen
      collection for HPV diagnosis.

PMID- 11463926
TI  - Demographic and behavioural profile of adults infected with chlamydia: a case
      control study.
AB  - OBJECTIVES: To determine which demographic and behavioural parameters are
      independently associated with chlamydial infection in adults. METHODS: Subjects
      were recruited prospectively from male and female attendees at a large clinic for
      sexually transmitted infections (STI). All subjects were tested for chlamydia and
      gonorrhoea and asked to complete a questionnaire addressing demography, sexual
      and non-sexual (including drug taking) behaviour, and history of STI. Cases were
      those attending with a new clinical episode and found to be infected with
      chlamydia, but who did not have gonorrhoea. A control group was selected randomly
      from those found to be negative on screening for both infections. RESULTS: 986
      cases and 1212 controls were recruited over one calendar year. The following were
      found to be independent risk factors for chlamydial infection on multivariate
      analysis (odds ratios with 95% confidence intervals in parentheses): being
      unmarried (1.8; 1.1-3.1); black Caribbean ethnicity (2; 1.5-2.7). Increasing age,
      fewer partners, and higher reported use of condoms were associated with a lower
      risk of infection. CONCLUSION: Black Caribbeans are at increased risk from
      chlamydia after controlling for sexual behaviour and socioeconomic status. Future
      research should seek an explanation elsewhere-for example, in terms of
      differences in sexual mixing or effectiveness of healthcare interventions.

PMID- 11463927
TI  - Sexually transmitted infections and vaginal douching in a population of female
      sex workers in Nairobi, Kenya.
AB  - OBJECTIVE: To assess the association between vaginal douching and sexually
      transmitted infections (STI) among a group of female sex workers (FSWs) in
      Nairobi, Kenya. METHODS: This study was part of a randomised, placebo controlled
      trial of monthly prophylaxis with 1 g of azithromycin to prevent STIs and HIV
      infection in a cohort of Nairobi FSWs. Consenting women were administered a
      questionnaire and screened for STIs. RESULTS: The seroprevalence of HIV-1 among
      543 FSWs screened was 30%. HIV infection was significantly associated with
      bacterial vaginosis (BV), trichomoniasis, gonorrhoea, and the presence of a
      genital ulcer. Regular douching was reported by 72% of the women, of whom the
      majority inserted fluids in the vagina, generally after each sexual intercourse.
      Water with soap was the fluid most often used (81%), followed by salty water
      (18%), water alone (9%), and a commercial antiseptic (5%). Douching in general
      and douching with soap and water were significantly associated with bacterial
      vaginosis (p = 0.05 and p = 0.04 respectively). There was a significant trend for
      increased frequency of douching and higher prevalence of BV. There was no direct
      relation observed between douching and risk for HIV infection or other STIs.
      CONCLUSION: The widespread habit of douching among African female sex workers was
      confirmed. The association between vaginal douching and BV is of concern, given
      the increased risk of HIV infection with BV, which has now been shown in several
      studies. It is unclear why we could not demonstrate a direct association between
      douching and HIV infection. Further research is required to better understand the
      complex relation between douching, risk for bacterial vaginosis, and risk for HIV
      and other STIs.

PMID- 11463928
TI  - Cost effectiveness analysis of a population based screening programme for
      asymptomatic Chlamydia trachomatis infections in women by means of home obtained
      urine specimens.
AB  - OBJECTIVES: To evaluate the cost effectiveness of a systematic screening
      programme for asymptomatic Chlamydia trachomatis infections in a female inner
      city population. To determine the sensitivity of the cost effectiveness analysis
      to variation in the probability of developing sequelae. METHODS: A decision tree
      was constructed to evaluate health effects of the programme, such as averted
      sequelae of chlamydial infection. Cost effectiveness from a societal perspective
      was estimated for screening by means of a ligase chain reaction on mailed, home
      obtained urine specimens, in a population with a C trachomatis test prevalence of
      2.9%. An extensive sensitivity analysis was performed for the probability of
      sequelae, the percentage of preventable pelvic inflammatory disease (PID), and
      the discount rate. RESULTS: The estimated net cost of curing one woman, aged 15
      40 years, of a C trachomatis infection is US$1210. To prevent one major outcome
      (PID, tubal factor infertility, ectopic pregnancy, chronic pelvic pain, or
      neonatal pneumonia), 479 women would have to be screened. The net cost of
      preventing one major outcome is $15 800. Changing the probability of PID after
      chlamydial infection from 5% to 25% decreases the net cost per major outcome
      averted from $28 300 to $6380, a reduction of 78%. Results were less sensitive to
      variations in estimates for other sequelae. The breakeven prevalence of the
      programme ranges from 6.4% for the scenario with all probabilities for
      complications set at the maximum value to a prevalence of 100% for probabilities
      set at the minimum value. CONCLUSIONS: Systematic screening of all women aged 15
      40 years for asymptomatic C trachomatis infections is not cost effective.
      Although the results of the analyses are sensitive to variation in the
      assumptions, the costs exceed the benefits, even in the most optimistic scenario.

PMID- 11463929
TI  - Protease inhibitor related type III hyperlipoproteinaemia is common and not
      associated with apolipoprotein-E E2/E2 phenotype.
AB  - OBJECTIVE: To determine the prevalence of type III hyperlipoproteinaemia in a
      cohort of HIV infected patients taking protease inhibitors and its correlation
      with the apolipoprotein-E2 isoform. DESIGN: Cross sectional study of 57
      consecutive HIV infected subjects taking protease inhibitor therapy for a median
      of 12.5 (1-29) months, seen in an outpatient HIV clinic. Controls were 17
      patients on non-nucleoside reverse transcriptor inhibitor therapy (NNRTI) for 9
      (1-19) months and 50 antiviral naive patients. METHODS: Fasting cholesterol,
      triglyceride, HDL cholesterol, lipoprotein (a), and glucose were measured.
      Lipoprotein electrophoresis was performed on patients with a cholesterol >6.5
      mmol/l and a triglyceride concentration of >4.5 mmol/l. Apolipoprotein-E
      phenotype was determined in serum. RESULTS: Dyslipidaemia was found in 43 (75%)
      PI treated patients-37 with triglyceride >2.3 mmol/l, 30 with cholesterol >6.5
      mmol/l, and nine with HDL cholesterol <0.9 mmol/l. 38% had a lipoprotein (a) >300
      mg/l. 11 patients (19.3%) had a type III hyperlipoproteinaemia pattern. Only one
      was homozygous for the E2 phenotype and none had clinical diabetes. An additional
      patient had a serum lipid profile compatible with type III hyperlipoproteinaemia
      and an E3/E2 phenotype in whom electrophoresis was not carried out before
      treatment. Six (35%) of the NNRTI and 16 (32%) of the antiviral naive patients
      had dyslipidaemia. 18 (31.6%) of the PI and none of the control patients had a
      cholesterol and/or triglyceride >8 mmol/l. CONCLUSION: Type III
      hyperlipoproteinaemia is common in this group of patients and need not be
      associated with the apolipoprotein-E2/E2 isoform. HIV protease inhibitors may
      interfere with lipoprotein receptor related protein.

PMID- 11463930
TI  - A novel condom policy for young attenders at a sexual health clinic.
AB  - OBJECTIVES: To review the uptake of a new service for condom provision in the
      under 16s. METHODS: A retrospective case note review of attenders at an inner
      London sexual health clinic. RESULTS: The service was audited over a 3 month
      period in the spring of 2000. There were 97 individual attendances, 94% (92) male
      and 6% (5) female. 89% (87) had never attended a sexual health service before.
      When asked how they had heard of the clinic 88% (86) said a friend had told them
      about the clinic. 66% (64) claimed not to be sexually active. CONCLUSIONS: A
      novel policy of condom distribution to groups of boys has been successfully
      piloted at an inner London sexual health clinic. This policy appears to be
      overcoming the reluctance of teenage boys to access sexual health services.

PMID- 11463931
TI  - Attendance by older patients at a genitourinary medicine clinic.
AB  - OBJECTIVES: To determine how patients aged 50 and above had been referred to a
      department of genitourinary medicine (GUM), why they had attended, their sexual
      histories, and what diagnoses were made. To identify any special sexual health
      needs in this group of patients. METHODS: A case note review was undertaken of
      all patients aged 50 and over attending the Portsmouth GUM department over a 3
      month period. RESULTS: There was a marked difference in reason for attendance
      between men and women in this older age group. Men were more likely to attend for
      a sexual health screen, often with minimal or no symptoms, following an
      extramarital or casual liaison. Women more commonly had symptoms causing
      difficulties with sexual intercourse with their regular partner. CONCLUSIONS:
      Older people present to GUM departments with a wide range of sexually associated
      problems. The diagnostic and management expertise available in GUM departments
      makes them ideal providers of sexual health care for this as well as younger age
      groups.

PMID- 11463933
TI  - Syringomata: an unusual differential diagnosis of anogenital warts.

PMID- 11463934
TI  - Female low sexual desire and sexually transmitted infections.

PMID- 11463935
TI  - Hepatitis B and C viruses and sexually transmitted disease patients in Jamaica.
AB  - OBJECTIVES: To determine the prevalence of hepatitis C virus (HCV), hepatitis B
      virus (HBV), human immunodeficiency virus (HIV) infections, and risk factors for
      HCV and HBV infections in sexually transmitted disease (STD) clinics in Jamaica.
      METHODS: A prospective observational cohort study was carried out. Blood was
      collected from 485 consecutive patients attending the comprehensive health centre
      in Kingston, Jamaica. Serum was tested using commercially prepared reagents and
      standard procedures for antibodies to HCV (anti-HCV), hepatitis B core antigen
      (anti-HBc), hepatitis B surface antigen (HBsAg), HIV-1 infection, and syphilitic
      infection. Sociodemographic and sexual characteristics of the patients were
      recorded for assessment as risk factors for HCV and HBV infections. RESULTS: None
      of the patients had anti-HCV, 21.0% had anti-HBc, 3.2% HBsAg, 2.5% tested
      positive for HIV-1, and 5.2% had reactive serological test for syphilis. Age was
      the only independent risk factor identified for anti-HBc positivity. CONCLUSIONS:
      The data obtained in this study were not in support of sexual transmission of HCV
      or HBV infections in Jamaica. Carefully designed multicentre studies could
      provide more consistent information on the transmission of these viruses by
      sexual routes.

PMID- 11463936
TI  - Neuropsychiatric reaction induced by clarithromycin in a patient on highly active
      antiretroviral therapy (HAART).

PMID- 11463939
TI  - Prevalence of Chlamydia trachomatis IgG antibodies in antenatal patients from
      Trinidad.

PMID- 11463940
TI  - Notice of redundancy.

PMID- 11463941
TI  - Is Mycoplasma hominis a vaginal pathogen?

PMID- 11463942
TI  - Response of hepatitis B induced membranoproliferative glomerulonephritis to
      HAART.

PMID- 11463943
TI  - Implications of random measurement error in studies adjusting for sexual
      behaviours.

PMID- 11463944
TI  - Cervical cytology smears in sexually transmitted infection clinics in the United
      Kingdom.

PMID- 11463945
TI  - Faith in stem cells.

PMID- 11463946
TI  - Oct-4: gatekeeper in the beginnings of mammalian development.
AB  - The Oct-4 POU transcription factor is expressed in mouse totipotent embryonic
      stem and germ cells. Differentiation of totipotent cells to somatic lineages
      occurs at the blastocyst stage and during gastrulation, simultaneously with Oct-4
      downregulation. Stem cell lines derived from the inner cell mass and the epiblast
      of the mouse embryo express Oct-4 only if undifferentiated. When embryonic stem
      cells are triggered to differentiate, Oct-4 is downregulated thus providing a
      model for the early events linked to somatic differentiation in the developing
      embryo. In vivo mutagenesis has shown that loss of Oct-4 at the blastocyst stage
      causes the cells of the inner cell mass to differentiate into trophectoderm
      cells. Recent experiments indicate that an Oct-4 expression level of roughly 50%
      150% of the endogenous amount in embryonic stem cells is permissive for self
      renewal and maintenance of totipotency. However, upregulation above these levels
      causes stem cells to express genes involved in the lineage differentiation of
      primitive endoderm. These novel advances along with latest findings on Oct-4
      associated factors, target genes, and dimerization ability, provide new insights
      into the understanding of the early steps regulating mammalian embryogenesis.

PMID- 11463947
TI  - Hypoxia-inducible factor and the development of stem cells of the cardiovascular
      system.
AB  - Decreased oxygen (O2) levels activate hypoxia-inducible factor (HIF-1) to induce
      genes involved in glycolysis, glucose transport, erythropoiesis, and
      angiogenesis. Mutations in various HIF-1 subunits have contributed to our
      understanding of the role hypoxia plays during early embryonic development in
      general and the cardiovascular system in particular. We propose that HIF-1 is
      important for the generation, proliferation, maintenance, and differentiation of
      the early cardiovascular system. Understanding aberrations in these hypoxic
      responses is important since they contribute to serious human disease such as
      ischemia and tumorigenesis. In this review we will focus on the critical role of
      O2 in regulating cardiovascular events during early embryonic development.

PMID- 11463948
TI  - Imprinting in the germ line.
AB  - Genomic imprinting is an epigenetic system of gene regulation in mammals. It
      determines the parent-of-origin-dependent expression of a small number of
      imprinted genes during development, i.e., the maternal allele is inactive while
      the paternal is active, or vice versa. Imprinting is imparted in the germ line
      and involves differential DNA methylation such that particular DNA regions become
      methylated in one sex of germ line but not in the other. Inheritance of these
      differential egg and sperm methylation states is then transmitted to somatic
      cells, where they lead to differential maternal and paternal allelic activity, or
      monoallelic expression. Increasing evidence indicates that the inherited and
      stable differential allelic methylation regulates monoallelic expression by
      influencing the activity of gene regulatory elements-for one allele the element
      is switched off by methylation, while for the other the element is left
      potentially active by the lack of methylation. An interesting feature of the germ
      line is that, despite the presence of genomic imprinting, either as imprints
      inherited from the zygote or as new imprints imparted according to germ cell sex,
      imprinted genes are biallelically expressed as if imprints were not present. One
      explanation for this observation is that imprints have no influence over the germ
      cell's transcriptional machinery, i.e., imprinting may be neutralized in the germ
      cell lineage. This phenomenon may have a common basis with other unique features
      of the germ line, such as totipotency, perhaps in some unique aspect of chromatin
      structure.

PMID- 11463949
TI  - Signal transduction: multiple pathways, multiple options for therapy.
AB  - Many aspects of cell behavior, such as growth, motility, differentiation, and
      apoptosis, are regulated by signals cells receive from their environment. Such
      signals are important, e.g., during embryonal development, wound healing,
      hematopoiesis, and in the regulation of the immune response, and may come from
      interactions with other cells or components of the extracellular matrix, or from
      binding of soluble signaling molecules to specific receptors at the cell
      membrane. Hereby different signaling pathways are initiated inside the cell.
      Perturbations of such signaling pathways are seen in several types of diseases,
      e.g., cancer, inflammatory conditions, and atherosclerosis. Thus, antagonists of
      several signaling pathways have potential clinical utility. Several such
      compounds are currently used or are in clinical trials; others are currently
      being analyzed in animal models.

PMID- 11463950
TI  - CD34- blood-derived human endothelial cell progenitors.
AB  - A subset of adult peripheral blood leukocytes functions as endothelial cell
      progenitors called angioblasts. They can incorporate into the vasculature in
      animal models of neovascularization and accelerate the restoration of blood flow
      to mouse ischemic limbs. Earlier reports suggested that CD34-expressing (CD34+)
      but not CD34+ cell-depleted (CD34-) leukocytes can differentiate into endothelial
      cells (EC) in vitro and in vivo. Recent findings suggest that CD14+ cells, which
      are typically CD34-, also have angioblast-like properties in vitro. To determine
      the identity of angioblasts, the potential of CD34+, CD34-, CD34- CD14+, and CD34
      CD14- cells to produce EC was compared. We show that a subset of monocyte (CD34-
      CD14+)-enriched cells can take on an EC-like phenotype in culture, but that the
      EC-like cells also express dendritic cell antigens. These findings suggest that
      monocytes differentiate into macrophages, dendritic cells, or EC depending on
      environmental cues. The data also demonstrate that angioblasts are more abundant
      in the blood than previously thought. Finally, we demonstrate that CD34- and CD34
      CD14+ cells incorporate into the endothelium of blood vessels in mouse ischemic
      limbs. However, incorporation of these cells requires co-injection with CD34+
      cells, indicating that leukocyte-leukocyte interactions may play a critical role
      in governing angioblast behavior in vivo.

PMID- 11463951
TI  - Interleukin 3 improves the ex vivo expansion of primitive human cord blood
      progenitor cells and maintains the engraftment potential of scid repopulating
      cells.
AB  - In umbilical cord blood (UCB) transplantation, the number of nucleated cells per
      kilogram is a major predictive and critical factor of hematopoietic recovery.
      Thus, ex vivo expansion of hematopoietic UCB progenitors could potentially
      accelerate engraftment. Whereas Flt-3 ligand (FL), stem cell factor (SCF), and
      thrombopoietin (TPO) are considered indispensable, the role of interleukin 3 (IL
      3) is still controversial: it has been reported either to support or abrogate the
      reconstituting ability of stem cells. By adding IL-3 we aimed to enhance the
      amplification of early and committed progenitor cells without impairing the long
      term engraftment of stem cells. Demonstrating a positive impact of IL-3 on the
      proliferation of all progenitor subsets, the amplification of CD34+ UCB cells was
      increased 20.9-fold +/- 5.4 (mean +/- standard error) in serum-free culture with
      FL, SCF, TPO, and IL-3 as opposed to 9.3-fold +/- 3.2 without IL-3 after 7 days.
      If IL-3 was included, primitive long-term culture-initiating cells and committed
      colony-forming cells were expanded 16.3-fold +/- 5.5 and 18.1-fold +/- 2.4,
      respectively, compared to 12.6-fold +/- 5.6 and 9.1-fold +/- 2.0 without IL-3.
      Analysis of cultured CD34+ UCB cells in sublethally irradiated nonobese
      diabetic/severe combined immunodeficient mice confirmed that cultured cells had
      preserved their repopulating potential. After 6 weeks, all mice showed
      multilineage engraftment with their bone marrow containing an average of 45%
      human CD45+ cells of the unmanipulated sample, 43% of cells after culture in the
      presence of IL-3, and 27% of cells after culture without IL-3. In combination
      with early acting cytokines, IL-3 therefore improves the ex vivo expansion of UCB
      stem and progenitor cells without impairing their engraftment potential.

PMID- 11463952
TI  - Effect of the hemoregulatory peptide (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 and MIP
      1alpha is reduced in bone marrow cultures from patients with chronic myeloid
      leukemia (CML).
AB  - The granulocyte-derived hemoregulatory peptide pyroGlu-Glu-Asp-Cys-Lys = pEEDCK
      is known to keep hematopoietic cells quiescent. When oxidized to its dimeric form
      (pEEDCK)2, it activates growth of hematopoietic progenitors in association with
      stroma-derived cytokines. (pEEDCK)2 has a Cys-Cys motif which is also a typical
      feature of the macrophage inflammatory protein (MIP-1alpha). The present study
      was designed to analyze differences between the response of normal and leukemic
      progenitor cells to (pEEDCK)2 or MIP-1alpha. When long-term bone marrow cultures
      (LTBMCs) were incubated with (pEEDCK)2 or MIP-1alpha and/or cytokines, the
      stimulatory effect on colony-forming units
      granulocyte/erythroid/macrophage/megakaryocyte of LTBMC from chronic myeloid
      leukemia (CML) patients was less than 50% compared to LTBMC from healthy humans.
      No difference in oncogene expression could be observed in LTBMC from CML patients
      regarding reduction of Philadelphia chromosome-associated transcription of the
      BCR-ABL gene. With respect to the expression of growth and differentiation
      associated genes (Galpha16, 5-lipoxygenase, phospholipaseA2, c-kit, and CD34),
      which were analyzed from LTBMC by semiquantitative reverse transcriptase
      polymerase chain reaction, the same transcription rate was observed in CML
      patients and healthy donors. However, two isoforms of a key enzyme of oxidative
      metabolism, carnitine palmitoyltransferase (CPT1A and CPT1B), showed 50-fold
      higher expression rates in LTBMC cells of healthy donors compared to CML
      patients. It is known that a decrease in oxidative metabolism is associated with
      an increase in redox equivalents in malignancy. This might result in a reduction
      of disulphide bonds in (pEEDCK)2 or MIP-1alpha, thus inducing a downregulation of
      these factors in bone marrow from CML patients.

PMID- 11463953
TI  - Promegapoietin-1a, an engineered chimeric IL-3 and Mpl-L receptor agonist,
      stimulates hematopoietic recovery in conventional and abbreviated schedules
      following radiation-induced myelosuppression in nonhuman primates.
AB  - Promegapoietin-1a (PMP-1a), a multifunctional agonist for the human interleukin 3
      and Mpl receptors, was evaluated for its ability to stimulate hematopoietic
      reconstitution in nonhuman primates following severe radiation-induced
      myelosuppression. Animals were total body x-irradiated (250 kVp) to 600 cGy total
      midline tissue dose. PMP-1a was administered s.c. in several protocols: A) daily
      (50 microg/kg) for 18 days; B) nine doses (5 microg/kg) every other day for 3
      weeks; C) a single high dose (100 microg/kg) at 20 hours, or D) a single high
      dose (100 microg/kg) at 1 hour following TBI. The irradiation controls received
      0.1% autologous serum for 18 consecutive days. Hematopoietic recovery was
      assessed by bone marrow clonogenic activity, peripheral blood cell nadirs,
      duration of cytopenias, time to recovery to cellular thresholds, and requirements
      for clinical support. PMP-1a, irrespective of administration schedule,
      significantly improved all platelet-related parameters: thrombocytopenia was
      eliminated, the severity of platelet nadirs was significantly improved, and
      recovery of platelet counts to > or =20,000/miccrol was significantly reduced in
      all PMP-1a-treated cohorts. As a consequence, all PMP-1a-treated cohorts were
      transfusion-independent. Neutrophil regeneration was augmented in all treatment
      schedules. Additionally, all PMP-1a-treated cohorts showed an improvement in red
      blood cell nadir and recovery. PMP-1a in conventional or abbreviated schedules
      induced significant thrombopoietic regeneration relative to the control cohort,
      whereas significant improvement in neutrophil recovery was schedule-dependent in
      radiation-myelosuppressed nonhuman primates.

PMID- 11463954
TI  - Interleukin-4 downregulates nuclear factor-erythroid 2 (NF-E2) expression in
      primary megakaryocytes and in megakaryoblastic cell lines.
AB  - The transcriptional factor nuclear factor-erythroid 2 (NF-E2) is one of the few
      transcription factors known to be functionally linked to the megakaryocytic
      lineage, where it regulates terminal megakaryocyte maturation and platelet
      formation. However, the regulation of NF-E2 expression in megakaryocytic cells
      has not been extensively evaluated. In particular, no data have been reported on
      the effect of negative regulators of megakaryocytopoiesis on NF-E2 expression.
      This study investigated the in vitro effects of two negative regulators of
      megakaryocytopoiesis, such as interleukin-4 (IL-4) and transforming growth factor
      beta1 (TGF-beta1) on the expression of NF-E2 transcription factor in
      megakaryoblastic cell lines (Hel and MK1) and in normal CD34-derived
      megakaryocytic cells. For this purpose, we used quantitative real-time reverse
      transcription-polymerase chain reaction (RT-PCR) to detect mRNA NF-E2 isoforms (a
      and f) and flow-cytometry analysis to evaluate NF-E2 protein expression. Our
      results demonstrated that TGF-beta1 did not inhibit NF-E2 mRNA and protein
      expression of either maturating or fully mature normal megakaryocytic cells as
      well as that of the two cell lines. By contrast, IL-4 downmodulates the
      expression of NF-E2 transcription factor at both mRNA and protein levels in
      normal maturating megakaryocytic cells and in the megakaryoblastic cell lines. NF
      E2 expression of normal mature megakaryocytes was not affected by IL-4. Thus, the
      results of the present investigation demonstrate that NF-E2 transcription factor
      is involved not only in terminal megakaryocyte maturation but also in the
      negative regulation of the early phase of megakaryocyte development.

PMID- 11463955
TI  - The molecular perspective: ultraviolet light and pyrimidine dimers.

PMID- 11463956
TI  - Type 2 diabetes in children: a problem lurking for India?

PMID- 11463957
TI  - Role of brain SPECT in neonates with hypoxic ischemic encephalopathy and its
      correlation with neurodevelopmental outcome.
AB  - OBJECTIVE: To study cerebral blood flow pattern seen on single photon emission
      computed tomography (SPECT) scan in neonates with hypoxic ischaemic
      encephalopathy (HIE) and to correlate it with immediate neurological status and
      neurodevelopmental outcome; and to compare it with Ultrasonogaphy (USG). DESIGN:
      Prospective cohort study. SETTING: Tertiary level Neonatal Intensive Care Unit.
      METHODS: All the neonates HIE stage 2 or 3 underwent SPECT scan and USG between
      the ages of 1-2 weeks. The pattern of deficit seen on SPECT scan was correlated
      with neurological status, duration of altered sensorium, severity of seizures and
      short-term neurodevelopmental outcome at 3 months. RESULTS: The commonest pattern
      of defect noted was parasagittal hypoperfusion. Babies with severe perfusion
      defect had higher incidence of difficult to control seizures and longer duration
      of altered sensorium. The positive predictive value of SPECT scan was 75% while
      that of USG was 60% and the negative predictive value of SPECT was 100% while
      that of USG was 76%, when neurodevelopmental outcome at 3 months was considered.
      CONCLUSION: SPECT scan is superior to ultrasonography in predicting
      neurodevelopmental outcome in babies with HIE.

PMID- 11463958
TI  - Prediction of mortality by application of PRISM score in intensive care unit.
AB  - OBJECTIVE: Prediction of mortality by application of Pediatric Risk of Mortality
      (PRISM) score in Pediatric Intensive Care Unit (PICU) patients under Indian
      circumstances. DESIGN: Prospective study. SETTING: PICU of a tertiary care multi
      specialty hospital. METHODS: 100 sick pediatric patients admitted consecutively
      in PICU were taken for this study. PRISM score was calculated. Hospital outcome
      was recorded as (died/survived). The predicted death was calculated by the
      formula: RESULTS: Of 100 patients, 18 died and 82 survived. By PRISM score 49
      children had the score of 1-9. The expected death in this group was 10.3% (n =
      5.03) and the observed death was 8.2% (n = 4). Among 45 children with the score
      of 10-19, the expected mortality was 21.2% (n = 9.6) and observed was 24.4% (n =
      11). There were 3 patients with the score of 20-29, the expected mortality in
      this group was 39.3% (n = 1.18) and observed mortality 33.3% (n = 1). There were
      3 patients with score > or = 30, observed death 66.3% (n = 2) and expected
      mortality was 74.7% (n = 2.24). There was no significant difference between
      expected and observed mortality in any group. (p > 0.5). ROC analysis showed area
      under the curve of 72%. CONCLUSION: PRISM score has good predictive value in
      assessing the probability of mortality in relation to children admitted to a PICU
      under Indian circumstances.

PMID- 11463959
TI  - National consultation to review the existing guidelines in ICDS scheme in the
      field of health and nutrition.

PMID- 11463960
TI  - Febrile seizures.

PMID- 11463961
TI  - 12. Multiple measurements and their simultaneous consideration.

PMID- 11463962
TI  - Risk factors for kernicterus in term babies with non-hemolytic jaundice.

PMID- 11463963
TI  - Pulse oximetry in asphyxiated newborns in the delivery room.

PMID- 11463964
TI  - Gastroesophageal reflux disease in children with cerebral palsy.

PMID- 11463965
TI  - Vitamin A supplementation in children with recurrent respiratory infections.

PMID- 11463966
TI  - Anthrax in an infant.

PMID- 11463967
TI  - Transfusion transmitted CMV infection in a neonate.

PMID- 11463968
TI  - Congenital cricopharyngeal achalasia.

PMID- 11463969
TI  - Langherhans cell histiocytosis in monozygotic twins.

PMID- 11463970
TI  - Trichotillomania.

PMID- 11463971
TI  - Hereditary wooly hair.

PMID- 11463972
TI  - Antigens in hepatitis B vaccines.

PMID- 11463974
TI  - Unusual foreign body in the neck.

PMID- 11463975
TI  - Hypothermia with nimesulide.

PMID- 11463976
TI  - Correlation of plasma color index with serum bilirubin in neonatal jaundice.

PMID- 11463977
TI  - Correlation of plasma color index with serum bilirubin in neonatal jaundice.

PMID- 11463979
TI  - Biochemical assessment of iodine deficiency disorder in Baroda and Dang districts
      of Gujarat State.

PMID- 11463981
TI  - Neurological prognosis in neonatal indirect hyperbilirubinemia.

PMID- 11463984
TI  - Expression of granzyme B and perforin in multiple myeloma.
AB  - Multiple myeloma (MM) remains an incurable disease by conventional therapy. MM
      tumor cells evade the immune system and can induce immunosuppression by producing
      immunomodifying agents such as TGF-beta, FasL, vascular endothelial growth factor
      and Muc-1. In the present study, we show that bone marrow cells from a patient
      suffering from MM IgG/k type, stage IIIA, when cultured, expressed granzyme B and
      perforin, normally expressed exclusively by cytotoxic T cells (CTLs) and natural
      killer (NK) cells. In addition, phenotypic analysis revealed that the cultured
      cells were activated antigen-presenting cells with NK targeting capacity. We
      propose that expression of these cytolytic enzymes may constitute an additional
      adoptive mechanism by the tumor cells to actively destroy the host immune
      effector cells.

PMID- 11463985
TI  - Activated T-cell and bispecific antibody immunotherapy for high-risk breast
      cancer. Bench to bedside.
AB  - Nontoxic approaches are needed to improve overall survival (OS) and progression
      free survival (PFS) for high-risk breast cancer. Combination immunotherapy (IT)
      consisting of activated T cells (ATC), interleukin-2 (IL-2), and CTL (GM-CSF) was
      given after peripheral blood stem cell transplant (PBSCT). There were no major
      toxicities and there appear to be improvements in OS and PFS over historical
      controls. In order to develop specific cytotoxic T lymphocytes (CTL), we combined
      ATC with the use of bispecific antibody (BiAb). By arming ATC with anti-CD3 x
      anti-HER2/neu BiAb (HER2BiAb), the approach converts nonspecific ATC into
      HER2/neu (HER2) specific CTL. ATC remain armed, kill tumor targets for days, and
      produce cytokines after binding to tumor. Arming ATC with BiAbs may prove to be
      effective for targeting a variety of tumors with and without high-dose
      chemotherapy.

PMID- 11463986
TI  - Factors determining the actual received dose intensity in a program of
      multicyclic dose-intensive alternating chemotherapy with sequential stem cell
      support.
AB  - Dose intensity has been related to clinical outcome in several solid tumors. We
      studied the influence of clinical and cellular parameters on dose intensity
      received in a series of 53 patients with metastatic breast cancer or advanced
      ovarian cancer. They received courses of cisplatin 120 mg/m(2) plus etoposide 600
      mg/m(2) alternating every 14 days with ifosfamide 8 g/m(2) plus paclitaxel 200-
      350 mg/m(2). Blood stem cell support was administered after every course except
      for the first one. Patients with excellent mobilization underwent immunomagnetic
      selection of CD34+ cells. We found a significant inverse correlation between the
      CD34+ cell dose infused and the delay for the administration of the next cycle. A
      CD34+ cell dose between 1.5 and 5 x 10(6)/kg per cycle was found to be feasible
      and was followed by a median delay of 1 day (not different from doses above 5 x
      10(6)/kg). Three factors independently predicted the actually received dose
      intensity in a multiple regression model (R(2) = 0.4): previous autologous
      transplantation, eligibility for immunomagnetic selection (excellent response to
      mobilization) and median CD34+ cell dose received along the treatment.

PMID- 11463987
TI  - Stem cell factor: biology and relevance to clinical practice.
AB  - The type III tyrosine kinase receptor c-KIT and its ligand stem cell factor (SCF;
      also known as KIT ligand, mast cell growth factor and steel factor) are closely
      involved in the regulation of a wide range of tissues at different stages of
      life. This review provides an outline of the discovery, structure and expression
      of SCF and c-KIT but concentrates on their respective roles in the regulation of
      human haemopoiesis and how this knowledge might be exploited in the clinical
      setting.

PMID- 11463988
TI  - Filgrastim (r-metHuG-CSF) in the 21st century: SD/01.
AB  - SD/01, a sustained-duration molecule, has been developed by adding a poly
      [ethylene glycol] molecule to the filgrastim molecule. The pegylation does not
      change the properties of filgrastim, except that the plasma clearance is
      decreased and plasma half-life is increased. Increasing the duration of the
      biological effects of filgrastim may offer certain groups of patients better
      benefits. Early clinical studies have been encouraging with no serious toxicities
      noted.

PMID- 11463989
TI  - Plasmapheresis for thrombotic thrombocytopenic purpura following bone marrow
      transplantation.
AB  - Recognition of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic
      syndrome (HUS) following bone marrow transplantation (BMT) has increased in
      recent years. The use of plasma exchange has greatly improved the outlook of de
      novo TTP. Fewer data are available on its use in post-BMT TTP but small
      uncontrolled series showed poor results with low response rates. We present here
      a case of a young patient who developed manifestations of TTP 10 months after BMT
      with complete recovery following treatment with plasma exchange for 1 month. This
      case suggests that plasma exchange could be life saving and should be tried in
      every patient with post-BMT TTP.

PMID- 11463990
TI  - Mesenchymal differentiation and organ distribution of established human stromal
      cell lines in NOD/SCID mice.
AB  - Two human stromal cell lines were established previously from bone marrow-derived
      primary long-term cultures by immortalization using the SV40 large T antigen and
      cellular cloning. After irradiation, the fibroblast-like cell lines L87/4 and
      L88/5 support hematopoietic differentiation of allogeneic cord blood cells in
      vitro. The stromal cells do not express CD34 and CD50, but some adhesion
      molecules and integrins, such as CD44, CD54 and CD58. Their expression profiles
      on RNA and protein levels are suggestive of their osteogenic potency. The quality
      and quantity of osteocalcin and osteopontin protein expression depended on the
      culture conditions. Expression of the osteogenic markers increased over time in
      culture, especially in cells growing in clusters. The stromal cells also
      expressed collagens I and V, but did not show any expression of collagens II and
      III. The potentially osteoblastic stromal cells were transplanted into NOD/ SCID
      recipient mice by intravenous injection and were found in various mesenchymal
      organs up to 10 weeks after transplantation. Osteocalcin-positive human stromal
      cells could be detected in the bone marrow, thymus, liver, brain and gut of the
      recipient animals. In summary, there is evidence that human bone-marrow-derived
      stromal cells have to be considered mesenchymal progenitors, persistently
      expressing osteogenic markers in vitro and in vivo.

PMID- 11463991
TI  - Detection of epithelial cells in hematopoietic organs of patients with breast
      cancer. Physiopathological significance and clinical consequences.
AB  - Breast cancer is the most frequent neoplastic disease in populations of developed
      countries. It will affect 1 of every 6 or 7 women during their lifetime. The
      disease eventually evolves to a metastatic stage, and currently appears to be not
      curable at that stage. Thus, understanding mechanisms that result in the
      establishment of tumor at sites distant from the primary location is of the
      utmost importance. Equally important is the definition of a metastatic state,
      especially in regard to the detection of micrometastases. Finally, the presence
      of circulating tumor cells in the peripheral blood of patients who undergo
      progenitor mobilization, collection and reinfusion may be of clinical
      significance in the setting of high-dose chemotherapy for breast cancer.

PMID- 11463992
TI  - Successful allogeneic bone marrow transplantation. Crucial roles of stromal cells
      in prevention of graft rejection.
AB  - We have previously found that a major histocompatibility complex (MHC)
      restriction exists between pluripotent hemopoietic stem cells (P-HSCs) and
      stromal cells. Based on this finding, we have recently found using chimerism
      resistant mouse combinations that successful allogeneic (allo) BMT can be
      executed by recruiting donor bone marrow stromal cells. The strategies include
      donor bone grafts under the skin, injection of whole bone marrow cells (BMCs)
      including stromal cells via the portal vein (PV), and injection of whole BMCs
      directly into the bone marrow cavity (intra-bone marrow [IBM] injection). In this
      paper, we show how stromal cells play crucial roles in overcoming chimerism
      resistant allo BMT.

PMID- 11463993
TI  - Immune reconstitution following transplantation of autologous peripheral CD34+
      cells.
AB  - The recovery of lymphocyte count, CD4+ and CD8+ T-cell subsets, natural killer
      (NK) cells and CD19+ B cells has been evaluated during the first 4 months after
      the infusion of autologous CD34+ peripheral blood progenitor cells (PBPC; group
      A; 33 patients) or autologous unselected PBPC (group B; 36 patients) for
      hematological malignancies. Lymphocyte count promptly recovered in both patient
      cohorts, although the repopulation of CD3+ T cells occurred more rapidly in group
      B compared with group A. The count of CD4+ T lymphocytes remained <200/microl
      during the study period in patients transplanted with CD34+ PBPC, being
      significantly lower compared with group B (p = 0.0019 and p = 0.0035 on days 30
      and 60, respectively). CD8+ T cells rapidly increased both in group A and B and
      CD4 to CD8 ratio was severely reduced. CD4+ and CD8+ T cells displayed an
      activated phenotype in both groups of patients, coexpressing the HLA-DR antigen
      throughout the study period. No differences in the repopulation kinetics of NK
      cells and CD19+ B cells were observed. Further investigations are encouraged to
      characterize T cell competence following transplantation of CD34+ PBPC.

PMID- 11463994
TI  - Clinical trials and survival curves: the shape of things to come.
AB  - Clinical trials remain the standard for introducing new treatments into the
      medical armamentarium. There is a wealth of information contained in survival
      curves that are the ultimate outcomes reported in most oncology clinical trials.
      Survival curves report interesting information about the disease and its response
      to treatment. Unfortunately, and all too often, the limitations of survival
      curves are not adequately presented in publications and alternative
      interpretations for the data are not meticulously delineated by authors. The
      danger inherent in any publication of survival is that the data are not
      sufficiently 'mature' to support the conclusions that are drawn. This would be of
      little consequence if medical decisions were not based upon reading the latest
      publication that is acclaimed to be definitive and settle the question 'once and
      for all.' Better understanding of survival curves and how they shape the future
      of clinical practice may reduce the dangers of these pitfalls.

PMID- 11463995
TI  - A case-control study of the effect of infant feeding on celiac disease.
AB  - AIMS: The aim of this study was to investigate the association between the
      duration of breast-feeding and the age at the first gluten introduction into the
      infant diet and the incidence and age at onset of celiac disease. METHODS: In a
      case-control study, 143 children with celiac disease and 137 randomly recruited
      gender- and age-matched control children were administered a standardized
      questionnaire. Multivariate-adjusted odds ratios (OR) as estimates of the
      relative risk and corresponding 95% confidence intervals (95% CI) were
      calculated. RESULTS: The risk of developing celiac disease decreased
      significantly by 63% for children breast-fed for more than 2 months (OR 0.37, 95%
      CI 0.21-0.64) as compared with children breast-fed for 2 months or less. The age
      at first gluten introduction had no significant influence on the incidence of
      celiac disease (OR 0.72, 95% CI 0.29-1.79 comparing first gluten introduction
      into infant diet >3 months vs. < or =3 months). CONCLUSIONS: A significant
      protective effect on the incidence of celiac disease was suggested by the
      duration of breast-feeding (partial breast-feeding as well as exclusive breast
      feeding). The data did not support an influence of the age at first dietary
      gluten exposure on the incidence of celiac disease. However, the age at first
      gluten exposure appeared to affect the age at onset of symptoms.

PMID- 11463996
TI  - Mild-to-moderate malnutrition alters glutathione, gamma-glutamyl-transpeptidase
      and glycine uptake in small intestinal brush-border vesicles of rhesus monkeys.
AB  - BACKGROUND: In India about 85% of pre-school children show evidence of mild-to
      moderate malnutrition. Consequences of severe malnutrition and protein deficiency
      are well reported by workers but little information is available on milder forms.
      METHODS: Mild-to-moderate protein energy malnourished (PEM) state was induced in
      12 monkeys by providing 2.42 g protein and 55 kcal kg(-1) day(-1) while 12
      controls were fed 4.84 g protein and 110 kcal kg(-1). After a 30-40% reduction in
      body weight as compared with their controls, the animals were killed and brush
      border membrane vesicles (BBMV) were prepared from three parts of small
      intestine. Purified vesicles were assayed for gamma-glutamyl-transpeptidase
      (GGTP), glutathione (GSH) and U-(14)C-glycine uptake. RESULTS: GGTP activity
      increased significantly while glutathione and uptake of glycine decreased
      significantly in all the three parts of small intestine. On nutritional
      rehabilitation of 9 weeks, the activity of GGTP, GSH and in vitro uptake of
      glycine amino acid recovered completely. CONCLUSION: The results of the present
      study indicates that even mild-to-moderate malnutrition should not be ignored
      during the development state.

PMID- 11463997
TI  - LDL and HDL oxidation and fatty acid composition in vegetarians.
AB  - The oxidation of low-density lipoproteins (LDL) and high-density lipoproteins
      (HDL) and fatty acid composition, which may affect the resistance of lipoproteins
      to oxidation, were determined in 24 lacto-ovo vegetarians. Vegetarian diets
      contain more essential polyunsaturated fatty acids (PUFAs). Therefore, the
      relationship between LDL and HDL oxidation resistance measured by the kinetics of
      the formation of fatty acid conjugated dienes (lag time, maximal rate of
      oxidation and maximal amount of conjugated dienes), LDL and HDL fatty acid
      composition and vitamin E content were evaluated. All parameters of in vitro
      oxidation were significantly lower in HDL when compared with LDL. The relative
      values of arachidonic, dihomo-gamma-linoleic and docosahexaenoic acid were
      significantly higher in HDL, alpha-linolenic acid content significantly lower,
      when compared with LDL; the peroxidizability index was significantly higher in
      HDL. The content of vitamin E was found more than 2-fold lower in HDL particles.
      The results show the importance of fatty acid composition in the resistance of
      LDL and HDL to oxidation and from this aspect, the composition of LDL isolated
      from vegetarians seems to be more favourable compared to HDL.

PMID- 11463998
TI  - Effects of gamma-irradiated fats on plasma lipid concentrations and hepatic
      cholesterol metabolism in rats.
AB  - Currently, there is a growing need for food irradiation that is effective in food
      preservation and quality improvement. Accordingly, this study was designed to
      observe the effects of gamma-irradiated dietary fat on plasma lipid
      concentrations and hepatic cholesterol metabolism in rats. Male rats were fed 5
      kGy-gamma-irradiated beef tallow (gammaBT), corn oil (gammaCO), perilla oil
      (gammaPO), and nonirradiated fats (BT, CO, and PO) for 6 weeks. The gamma
      irradiated fat feeding did not affect the plasma lipid concentrations. However,
      the hepatic cholesterol content was significantly higher in the rats fed gamma-CO
      as compared with the rats fed nonirradiated CO (40.0 vs. 28.2 mg/g liver). The
      hepatic HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activities were
      not significantly different between the controls and the gamma-irradiated fat fed
      groups. However, the hepatic ACAT (acyl-CoA:cholesterol acyltransferase) activity
      was significantly lower in the gammaPO group as compared with its control group
      (138.2 vs. 404.5 pmol min(-1) mg(-1)). Among the nonirradiated groups, the ACAT
      activities of the CO and PO groups were higher than that of the BT group. The
      amounts of coprostanone, cholesterol, and total fecal neutral sterol were
      significantly higher in the gammaPO group as compared with the other groups.
      These results indicate that although slight changes in the lipid metabolism were
      observed as a result of 5-kGy-gamma-irradiated fat feeding, they were relative to
      the fat type and had no harmful consequences.

PMID- 11463999
TI  - A study of intensified dietary support in underweight candidates for lung
      transplantation.
AB  - BACKGROUND: No data is available on dietary intervention in candidates for lung
      transplantation and on the effect of different strategies for dietary support in
      this cohort. AIM: We therefore wanted to evaluate the effects of intensified
      nutritional support compared with simple support on energy intake and nutritional
      status. METHOD: Our participants were underweight (n = 42) and normal-weight
      (control group, n = 29) candidates for lung transplantation. The underweight
      patients were randomized into two groups. Group A received intensified dietary
      counselling, ready-made liquid nutritional supplements free of charge and regular
      follow-ups, while group B received only one session of individual dietary
      counselling, no supplements and no follow-ups. RESULTS: The mean intervention
      time was 21 weeks. Groups A and B both increased their energy intake and gained
      weight. Group A increased their energy intake from a median of 8.7 to 10.1 MJ (p
      < 0.01 compared with the control group after intervention) and gained a mean of
      2.9 kg body weight (95% CI 1.2; 4.7, p = 0.005 compared with the control group),
      while group B increased from 7.4 to 10.8 MJ (p = 0.005) and gained 2.3 kg (1.2;
      3.3, p = 0.002). Only group B increased their fat-free mass. In this group, an
      increase in O(2) saturation and a decrease in PaCO(2) were suggested. None of the
      groups improved its physical performance. CONCLUSION: In candidates for lung
      transplantation we were unable to confirm the hypothesis that intensified
      nutritional support compared with a simple support increased compliance. Both
      groups achieved the goal for energy intake and gained weight.

PMID- 11464000
TI  - Evaluation of various rapid chloride tests for assessing urinary NaCl excretion.
AB  - BACKGROUND/AIMS: The evidence linking NaCl intake to high blood pressure and
      probably to other diseases has become stronger. Therefore, a population-wide
      reduction of NaCl intake is generally recommended. Measuring NaCl excretion in
      urine is the preferred method for estimating dietary NaCl intake. Rapid tests
      measuring urinary NaCl excretion might be useful for self-monitoring the
      individual NaCl consumption. METHODS: The accuracy of four rapid tests measuring
      chloride content in urine was assessed. Three tests were originally not designed
      for urine analysis, but for water and food analysis. Totally 204 urine samples
      were analysed both with the 4 different rapid tests and with quantitative routine
      laboratory procedures for chloride and sodium. RESULTS: Chloride and sodium were
      highly correlated (r = 0.96), indicating chloride determination as a reasonable
      method to assess sodium and NaCl contents in urine. Accuracy of the rapid tests
      was acceptable in three cases. The drawback of two tests was their narrow
      calibration range, so that most urine samples had to be diluted. Use of one test
      showed problems in interpreting its results because the decolouration of the test
      pads was difficult to recognize. CONCLUSION: It is concluded that rapid chloride
      tests designed for water analysis might be suitable to determine NaCl in urine
      samples.

PMID- 11464001
TI  - Nutritional disorders among workers in North China during national turmoil.
AB  - Previously undescribed disorders of nutrition of thiamin, niacin and pyridoxin
      were observed among the poor people of North China during periods of prolonged
      deprivation. These disorders were often elicited or exacerbated by physical
      exertion. Thiamin deficiency syndromes included great toe pain, heel pain,
      temporomandibular joint click, and painful click of the knee. Syndromes of niacin
      deficiency included pellagral scrotal dermatitis, hypersecretion of ear wax, and
      night terrors. Episodic nocturnal motor hyperfunction was caused by pyridoxin
      deficiency. Several cases with cardiovascular diseases were observed in which
      nutritional debt appeared to occur simultaneously with oxygen debt following
      severe physical labor. Intramuscular thiamin HCl ameliorated symptoms of
      impending stroke. Persons with the same symptoms who did not receive thiamin
      progressed to fatal stroke.

PMID- 11464002
TI  - Consensus statement on submission and publication of manuscripts.

PMID- 11464003
TI  - New 'surgical innovation' as a revolution.

PMID- 11464004
TI  - Icing on the cake: a modified technique to seal the raw parenchymal surface of a
      split liver transplantation with fibrin glue.

PMID- 11464005
TI  - Preoperative adjuvant radiochemotherapy may increase the risk in patients
      undergoing thoracoabdominal esophageal resections.
AB  - BACKGROUND/AIM: Fatigue and malaise are common symptoms after radiochemotherapy
      which could affect patients' working capacity and add to the subsequent
      postoperative risk. The aim of the study was to investigate whether neoadjuvant
      radiochemotherapy in patients scheduled for a thoracoabdominal resection impairs
      their working capacity and adds to the postoperative risk. PATIENTS AND METHODS:
      29 patients with resectable tumors (T(3) or N(1)) and a working capacity of > or
      =80 W on a bicycle test were included into the study. The tumor stage was
      determined by endoscopic ultrasound and computed tomography scan. The patients
      were given neoadjuvant radiochemotherapy during 38 days, consisting of two cycles
      of 5-fluorouracil (1,000 mg/m(2)) daily during 5 days and cisplatinum (100
      mg/m(2)) on two occasions. Accelerated radiochemotherapy to a total dose of 40.8
      Gy was given. Surgery was planned 4-6 weeks after completion of therapy. The
      patients had a bicycle test before induction of neoadjuvant treatment and 2-5
      days prior to the operation. RESULTS: Three patients died already during the
      course of neoadjuvant treatment. The 26 remaining patients who had a bicycle test
      decreased their working capacity by a mean of 30 W (p < 0.0001). Ten patients had
      a decrease of their working capacity to < or = 90 W, of whom 6 died within 3
      months postoperatively, and of the patients who had the working capacity
      decreased to < or = 80 W, 4 out of 5 died during the corresponding postoperative
      period. None of the patients, who performed >100 W at the second preoperative
      bicycle test died. CONCLUSIONS: Preoperative adjuvant radiochemotherapy,
      according to the present schedule, clearly exerts a detrimental effect on the
      patients' working capacity. A physical performance, at the time of the operation,
      < or = 80-90 W strongly predicts the subsequent postoperative risk. Similar
      adjuvant therapies may, therefore, in fact be harmful to some patients scheduled
      for a thoracoabdominal resection.

PMID- 11464006
TI  - Correlation between endoscopic and angiographic findings in patients with
      esophageal and isolated gastric varices.
AB  - BACKGROUND/AIM: The correlation between angiographic vascular patterns and
      endoscopic findings in portal hypertension is not sufficiently known, and
      knowledge of the vascular anatomy may contribute to an improvement in endoscopic
      embolization and transjugular retrograde obliteration procedures. We propose a
      new vascular map that should prove useful for this purpose. METHODS: Between
      April 1985 and December 1997 we performed percutaneous transhepatic portography
      in a selected group of 75 patients (16 women and 59 men), aged 43-71 years, from
      whom informed consent was obtained. All patients had been diagnosed
      endoscopically as having either esophageal or isolated gastric varices. According
      to the Child-Pugh classification, class A, B, and C cirrhosis was seen in 19, 40,
      and 16 patients, respectively. We created a vascular map of esophageal and
      isolated gastric varices, based on the opacification of the portal venous
      collaterals on percutaneous transhepatic portography. We compared the patients in
      both variceal groups in terms of portal venous pressure, main blood supply, and
      drainage routes. RESULTS: We found that the portal collateral system was divided
      into two systems: the portoazygos venous system and the portophrenic venous
      system. The former contributed to the formation of esophageal and cardiac varices
      and the latter to the formation of isolated gastric varices located at the fundus
      or at both the cardia and fundus. The left gastric vein participated as blood
      supply in 70% of the isolated gastric varices and in 100% of the esophageal
      varices (p < 0.01). The posterior gastric vein participated as blood supply in
      70% of the isolated gastric varices and in 24% of the esophageal varices (p <
      0.01). We classified the main blood drainage routes of isolated gastric varices
      functionally into three types: gastrorenal shunt (85%), gastrophrenic shunt
      (10%), and gastropericardiac shunt (5%). The portal venous pressure in patients
      with esophageal varices was 358 +/- 66 mm H(2)O, whereas in patients with
      isolated gastric varices it was 262 +/- 44 mm H(2)O (p < 0.01). CONCLUSION: We
      suggest that this new vascular map will be useful in endoscopic embolization and
      transjugular retrograde obliteration procedures for esophageal and isolated
      gastric varices.

PMID- 11464007
TI  - Anterior versus posterior slippage: two different types of eccentric pouch
      dilatation in patients with adjustable laparoscopic gastric banding.
AB  - PURPOSE: To describe two different types of band dislocation that may occur in
      morbidly obese patients following adjustable laparoscopic gastric banding (ALGB)
      with the LAP-BAND. MATERIALS AND METHODS: 170 morbidly obese patients were
      treated with an LAP-BAND at our institution. In the first 20 patients the band
      was positioned transbursally, which means that the lesser sac is penetrated
      during laparoscopic band implantation. In the following 150 patients the
      operation technique was changed to suprabursal band positioning where the lesser
      sac is not penetrated. Plain radiographs and single contrast studies of all
      patients who developed band instability in the follow-up were analyzed
      retrospectively and compared to the clinical and intraoperative findings and to
      the operation technique used. RESULTS: Over a time period of 3.5 years 'posterior
      slippage' occurred in all 20 patients with transbursal band placement, but it
      never occurred after suprabursal band placement. Never- theless 4 patients with
      suprabursal band placement presented with an eccentric pouch dilatation,
      secondary to 'anterior slippage' after the seromuscular stitches had burst on the
      anterior and superior surface of the band. All these patients presented with food
      intolerance and all of them had to be reoperated. The radiographic findings were
      pathognomonic for each type of band dislocation. CONCLUSION: Band dislocation is
      a known major complication that may occur following ALGB and it may present in
      two different forms. While 'posterior slippage' can be avoided if the band is
      placed suprabursally, 'anterior slippage' may still occur. It is important to be
      familiar with both types of band dislocation since they require early detection
      and surgical band replacement or band refixation.

PMID- 11464008
TI  - Pylorus-preserving total pancreatectomy. Early and late results.
AB  - BACKGROUND/AIMS: Preservation of the pylorus is an accepted alternative procedure
      to the classical Whipple operation for pancreatic head resection but data
      describing its value for total pancreatectomy are sparse. METHODS: A prospective
      analysis of 22 total pancreatectomies performed in a consecutive series of 436
      pancreatic resections from 1.11.93 to 1.5.99. RESULTS: 11 patients underwent
      total pancreatectomy with preservation of the pylorus. Histopathological
      examination revealed pancreatic adenocarcinoma in 16 cases and duodenal
      adenocarcinoma in 1 patient, 5 patients had other types of pancreatic neoplasm.
      In-hospital mortality was 4.5% (n = 1), cumulative morbidity was 59% and
      reoperations were performed in 9.1% of cases (n = 2). Median follow-up was 37
      months (range 5-66). 62% of patients (n = 13) developed tumor recurrence and 13
      patients died during the follow-up period with 10 deaths being cancer related.
      There was no difference concerning postoperative and follow-up morbidity of
      survival between patients undergoing pylorus-preserving total pancreatectomy or
      pancreatectomy with gastrectomy. However, postoperative body weight was increased
      3, 6, 9 and 12 months following preservation of the pylorus. CONCLUSION: Total
      pancreatectomy with preservation of the pylorus is a feasible type of resection
      for all types of pancreatic or ampullary tumors, which shows a similar morbidity
      and long-term survival but improved nutritional recovery compared with standard
      total pancreatectomy.

PMID- 11464009
TI  - Hepatic tissue engineering on 3-dimensional biodegradable polymers within a
      pulsatile flow bioreactor.
AB  - BACKGROUND: An optimal method for hepatocyte transplantation is not yet
      determined. With the principles of tissue engineering in vitro conditioning of
      hepatocytes on biodegradable polymer in a flow bioreactor before implantation
      forming spheroids may achieve increased cell mass and function to replace lost
      organ function in vivo. METHODS: Biodegradable poly-L-lactic (PLLA) polymer discs
      were seeded with rat hepatocytes in a concentration of 10 x 10(6) cells per ml
      and exposed to a medium flow of 24 ml/min for 1, 2, 4 and 6 days. The number and
      diameter of spheroidal aggregates was measured by phase-contrast microscopy. H&E
      histology was performed. Albumin production as hepatocyte specific function was
      determined by ELISA. RESULTS: Spheroids of viable hepatocytes of 50-200 microm in
      diameter were formed. Both the number and diameter of the spheroids increased
      during the first 2 days and then remained constant until day 6. Albumin
      production was maintained throughout the culture period. CONCLUSION: Short (2- 3
      days) pre-transplant conditioning of hepatocytes in a flow bioreactor on
      biodegradable PLLA resulted in formation of spheroids with a liver-like
      morphology and preserved specific metabolic function. Tissue engineered
      hepatocyte spheroids on polymer may represent a functionally active and easy
      transplantable neotissue and may serve as an in vivo substitute for lost liver
      function.

PMID- 11464010
TI  - In vitro function of islets of Langerhans encapsulated with a membrane of porcine
      chondrocytes for immunoisolation.
AB  - BACKGROUND/AIMS: Widespread clinical application of islet transplantation remains
      restricted, because of insufficient methods to prevent rejection and autoimmune
      destruction of islet grafts. In this study we demonstrate long-term function of
      islets of Langerhans within a capsule of porcine chondrocytes which may serve as
      an immunoisolation barrier utilizing the immunoprivileged properties of the
      chondrocyte matrix. METHODS: Islets of Langerhans were isolated from Lewis rats,
      seeded on biodegradable polyglycolic acid polymer, and encapsulated with a
      monolayer of porcine chondrocytes. The encapsulated constructs and controls were
      kept in culture for 5 weeks. One group was exposed to a glucose challenge every
      5th day. The insulin concentration of the culture medium was measured.
      Histological and insulin-immunohistochemical studies were performed. RESULTS:
      Hematoxylin and eosin histology demonstrated viability of the islets of
      Langerhans. The intact morphology was demonstrated by Heidenhain staining.
      Toluidine blue showed viability of surrounding chondrocyte layers.
      Immunohistochemistry was positive for insulin within the beta cells of the
      islets. Both encapsulated constructs and nonencapsulated controls showed
      increasing insulin levels after glucose challenge. CONCLUSIONS: We can tissue
      engineer a chondrocyte encapsulation membrane which permits diffusion of glucose
      and insulin. Islets of Langerhans survive within the chondrocyte capsule, and the
      glucose/insulin feedback mechanism remains intact.

PMID- 11464011
TI  - Self-expandable metallic stent therapy of esophagojejunal stricture in a stapled
      anastomosis: a case report and review of the literature.
AB  - The introduction of the stapler apparatus has provided safe and effective
      gastrointestinal anastomotic surgical operations for most surgeons. However, the
      major disadvantage of stapler surgery is an increased risk of anastomotic
      stricture formation. Treatment of this kind of stricture is performed mainly by
      using endoscopic balloon dilators. However, this therapy may fail or the patient
      may become reactive or uncooperative during dilatation sessions. Herein, we
      present a case to show the successful and uncomplicated insertion of a self
      expanding metallic stent into an esophagojejunal anastomotic stricture which
      developed 1 month after total gastrectomy and stapled esophagojejunal anastomosis
      in a patient with gastric carcinoma. This is the 3rd report in the literature.

PMID- 11464012
TI  - Video mediastinoscopic division of a congenital esophagobronchial fistula with
      esophageal diverticulum by a paraesophageal approach.
AB  - We treated a patient with an esophagobronchial fistula accompanied by stomach
      cancer. Using an endo-stapling technique, the fistula was divided video
      mediastinoscopically by a paraesophageal approach through the esophageal hiatus
      in the diaphragm.

PMID- 11464013
TI  - Carcinosarcoma of the esophagus--pattern of recurrence.
AB  - Carcinosarcoma of the esophagus is a rare malignant neoplasm, predominantly
      affecting men in their seventh decade of life. While presenting symptoms and
      anatomic location of squamous cell and carcinosarcoma of the esophagus are
      similar, the latter often presents as a large intraluminal polypoid mass on
      barium esophagram. The more favorable prognosis associated with carcinosarcoma
      versus other esophageal neoplasms has been attributed to early onset of symptoms,
      resulting in prompt diagnosis, and a lower propensity for tumor invasion. We
      report the case of an elderly woman presenting with dysphagia who was initially
      diagnosed with esophageal leyomyosarcoma. Final tumor pathology showed esophageal
      carcinosarcoma.

PMID- 11464014
TI  - Treatment of devastating postgastrectomy symptoms: the potential role of jejunal
      pouch reconstruction.
AB  - After gastrectomy a few patients develop severe symptoms and malnutrition. There
      are probably several reasons for this, such as insufficient gastric reservoir
      function, malassimilation, diarrhea and dumping. The patient presented here
      developed severe malnutrition after partial gastrectomy and his weight gradually
      decreased from 95 to 40 kg during the first 6 postoperative years. His major
      complaint was postprandial vomiting and early satiety. During the course of his
      illness, he was repeatedly investigated with computerized tomography scans,
      repeated endoscopies with biopsies, barium examinations, etc. Finally the only
      positive finding was bacterial intestinal overgrowth, but antibiotic treatment
      did not improve his condition. After repeated periods of parenteral nutrition or
      enteral tube feeding, an S-shaped jejunal pouch was attached to the gastric
      remnant. Dual-energy X-ray absorptiometry was used to examine the body
      composition and bone density in the immediate postoperative period and 1 year
      after the operation. During the first postoperative year he gained 11 kg weight
      and reported an essentially normal food intake. Both laboratory and clinical
      parameters improved and a gain in lean body mass was recorded. Patients with
      severe postgastrectomy symptoms, with no other plausible explanation than
      nonexistent or insufficient gastric reservoir function, may benefit from re
      reconstruction with a jejunal pouch.

PMID- 11464015
TI  - Proximal gastric diverticulum after anterior lesser curve seromyotomy.
AB  - A case of gastric diverticulum arising in a patient who had previously undergone
      anterior lesser curve seromyotomy for chronic duodenal ulcer disease is reported.
      The endoscopic appearance of this lesion is described and the potential
      mechanisms of causation are reviewed. The clinical relevance of this rare finding
      is examined with emphasis on the need for an index of awareness of this
      abnormality on the part of endoscopists and in particular, on the risks of
      injudicious biopsy of such a diverticulum.

PMID- 11464016
TI  - Vena cava stenting and portorenal shunt in Budd-Chiari syndrome: combination of
      the 'modern' and the 'classical'.
AB  - We have treated a 33-year-old Budd-Chiari patient (due to antiphospholipid
      syndrome) with a history of myocardial infarction by placing a vascular stent in
      the inferior vena cava and performing a portorenal shunt with three objectives:
      (1) to perform a shunt operation on a Budd-Chiari patient with good hepatic
      functional reserve, (2) to avoid a thoracotomy and manipulation of the heart in a
      patient with a cardiac thrombus and a history of myocardial infarction and (3) to
      avoid a synthetic graft in a patient with antiphospholipid syndrome. Vena cava
      stenting and portorenal shunt make a useful combination which should be included
      in the armamentarium of the hepatobiliary surgeon.

PMID- 11464017
TI  - Successful treatment of dissemination of hepatocellular carcinoma to the pleura
      and diaphragm after percutaneous liver biopsy.
AB  - BACKGROUND/AIM: Treatment for dissemination of hepatocellular carcinoma to the
      pleura and diaphragm following percutaneous needle biopsy has not been
      established. METHODS: The case of a 57-year-old man who underwent percutaneous
      needle biopsy for liver tumor is presented. RESULTS: Ten months after resection
      of the tumor (moderately differentiated hepatocellular carcinoma), masses in the
      right pleural cavity and on the diaphragm were detected by computed tomography.
      Resections of the masses with surrounding tissue and the diaphragm and wedge
      resection of the right lung were performed. A wide range of the pleura and the
      diaphragm was coagulated with an argon beam coagulator. The patient is in good
      health without recurrence 4 years after the operation. CONCLUSION: Aggressive
      surgical treatment should be considered for patients with dissemination of
      hepatocellular carcinoma by needle biopsy when the lesions are limited.

PMID- 11464018
TI  - Acute cholecystitis secondary to hemobilia after percutaneous liver biopsy.
AB  - A case of obstructive acute cholecystitis following percutaneous liver biopsy is
      presented. The patient complained of intense and continuous pain in the right
      upper quadrant of the abdomen 2 days after the liver biopsy. On abdominal
      examination, Murphy's sign was present. Hemogram revealed a fall in the
      hematocrit level from 44 to 38 because of hemobilia. Ultrasonography showed a
      dilated gallbladder with moderate thickness of the wall and a blood clot of 20 x
      9 mm inside. The patient was subjected to laparoscopic cholecystectomy. The acute
      inflammation of the gallbladder was secondary to obstruction of the cystic duct
      by the blood clot. The postoperative period was uneventful.

PMID- 11464019
TI  - Splenic rupture following ESWL for a pancreatic duct calculus.
AB  - Extracorporeal shock wave lithotripsy (ESWL) is an established and extensively
      used treatment alternative for urinary calculi. It is also an established method
      of dealing with pancreatic duct calculi complementing endoscopic techniques in
      selected cases. Three reports of splenic injury following and probably caused by
      ESWL for urinary calculi have previously been published. We report a case of
      splenic rupture presenting with life-threatening hemorrhage 6 days after a single
      ESWL therapy session for pancreatic duct calculi.

PMID- 11464020
TI  - Splenic abscess after lithotripsy of pancreatic duct stones.
AB  - We describe a case of splenic abscess following lithotripsy of pancreatic stones,
      for which emergency splenectomy eventually had to be performed. It is important
      to be aware of this complication, because splenic abscess is still a life
      threatening entity.

PMID- 11464021
TI  - Arthritis as a rare extra-intestinal manifestation of acute sigmoid
      diverticulitis.
AB  - BACKGROUND: A causal association between acute diverticulitis of the sigmoid
      colon and arthritis has rarely been reported. CASE REPORT: We report the case of
      a 60-year-old patient who developed migrating arthritis of the knee and ankle
      during the recurring episode of acute diverticulitis of the sigmoid colon.
      Treatment with NSAIDs and antibiotics had little effect on joint disease, but
      medical treatment was successful in reducing the diverticulitis-related symptoms.
      Arthritis promptly improved after surgical resection of the sigmoid colon, and 30
      months later the patient is free of symptoms in the previously affected joints.
      CONCLUSIONS: Five cases of diverticulitis-associated arthritis have been
      reported. The similar case reported here reconfirms that joint disease has a
      limited response to medical approaches. Colon resection is recommended for
      patients with diverticulitis-associated arthritis which does not respond promptly
      to antibiotic therapy.

PMID- 11464022
TI  - Multiple idiopathic small bowel strictures: report of three cases.
AB  - Multiple strictures of the small bowel are relatively rare. In many cases, a
      distinct cause can be defined, but some strictures are unexplainable by any
      specific mechanism and have been termed 'idiopathic' small bowel strictures. We
      present 3 cases of multiple small bowel strictures in which the affected segments
      were studied with perioperative photoplethysmography, in vivo specimen
      angiography and pathology. Neither photoplethysmographic alterations nor
      structural vascular lesions were found.

PMID- 11464023
TI  - Interposed colon between remnants of the small intestine exhibits small bowel
      features in a patient with short bowel syndrome.
AB  - We describe herein the case of a 48-year-old man who underwent emergency massive
      resection of the small intestine due to a strangulated ileus, which led to short
      bowel syndrome (SBS), as he was left with only 7 cm of jejunum and 8 cm of ileum
      with ileocecal valve. He then received interposition of a colon segment between
      the jejunum and ileum remnants isoperistaltically. For 24 months after the
      operation, he has been able to tolerate oral intake, but still requires partial
      home parenteral nutritional support during the night on a bimonthly basis.
      Biochemical and nutritional parameters, including the analysis of minerals and
      trace elements, indicated that the patient was in relatively good health.
      Histological examination revealed that the mucosa of the interposed colon showed
      hypertrophy and hyperplasia of the crypt glands, and cells resembling Paneth
      cells which are usually seen in the small intestine, suggesting that the colon
      segment exhibits adaptive changes to the small intestine. Colon interposition may
      be a useful technique in patients with SBS when the small bowel is too short for
      the other surgical considerations.

PMID- 11464024
TI  - Small bowel perforation after extracorporeal shockwave lithotripsy of an ureter
      stone.
AB  - A 60-year-old man was treated by extracorporeal shock wave lithotripsy (ESWL) for
      an impacted ureter stone. Two days after the procedure he developed an acute
      abdomen. On laparotomy, a small bowel perforation in the area of an adhesion to
      the abdominal wall was found. The adherent intestinal segment was located exactly
      in the range of the ESWL field, so that excluding further reasons the shockwave
      lithotripsy must be assumed to be causative.

PMID- 11464025
TI  - Novel operative management of primary mesenteric volvulus.
AB  - Mesenteric volvulus is a potentially life-threatening condition. Little
      information is available for the recommended treatment of viable bowel and
      virtually no information is available for the suggested elective treatment of a
      mesenteric volvulus. This communication details a series of enteropexies that
      were successful in the management of this disorder.

PMID- 11464026
TI  - Granulomatous appendicitis revisited: report of a case.
AB  - BACKGROUND: Isolated granulomatous appendicitis is uncommon and previously was
      considered to be a form of localised Crohn's disease. However more recent series
      have noted that relapse is rare after appendicectomy and concluded that the
      condition is a distinct entity unrelated to Crohn's disease. Following a case of
      granulomatous appendicitis at St. Vincent's University Hospital Dublin, the
      condition was reviewed and the results are detailed herein. METHODS: A case of
      granulomatous appendicitis is presented with discussion of 4 previous cases
      encountered in our practice and the literature is reviewed. RESULTS: The clinical
      presentation was sub-acute appendicitis with a mass palpable in the right iliac
      fossa. At operation an enlarged, inflamed appendix with a broad base was noted
      and appendicectomy performed. Histopathology showed numerous granulomata on
      microscopic examination. The yersinia serology tests were negative. Review of
      computerised histopathology records in the hospital for the last 7 years showed 4
      additional cases of granulomatous appendicitis. This is a total of 5 of 1,615
      appendectomies (an incidence of 0.31%). In all cases, the post-operative course
      was uneventful and the patients have had no further complaints. CONCLUSION: This
      small series provides further evidence that granulomatous appendicitis is a
      distinct clinical entity unrelated to Crohn's disease and is cured by
      appendicectomy. It should be suspected when there is a sub-acute onset of
      appendicitis and an enlarged, broad-based appendix is found at operation.

PMID- 11464028
TI  - Bladder cancer. I. Molecular and genetic basis of carcinogenesis.
AB  - The transformation of a normal into a malignant cell is a multistep mechanism,
      which involves various alterations on the molecular and genetic level. These
      molecular alterations occur spontaneously or are induced by carcinogens (e.g.
      naphthylamine--a component of cigarette smoke and one of the most important
      carcinogens leading to bladder tumor carcinogenesis). This report summarizes some
      of the most important molecular and genetic alterations in bladder cancer. As in
      most other malignancies the generation of bladder cancer is caused by the
      accumulation of various molecular changes. The expression of oncogenes (ras, erbB
      2 and EGF receptor), tumor-suppressor genes (Rb, p53), cell-cycle genes (p15,
      p16) and DNA-repair genes is altered mostly by mutation or chromosomal
      aberration. Loss of heterozygosity of chromosome 9p and 9q has been shown to be a
      crucial event in the transition of normal urothelium to papillary transitional
      cell carcinoma while p53 is primarily involved in the development of carcinoma in
      situ.

PMID- 11464029
TI  - Bladder cancer. II. Molecular aspects and diagnosis.
AB  - The current system used to classify bladder carcinoma by stage and histological
      grade is very useful, yet still has limited ability to predict the natural
      history, or treated natural history, of a bladder tumor. Cystoscopy and urine
      cytology are currently the gold standard in the diagnosis and follow-up of
      bladder cancer. Classical urine cytology, however, at least in the diagnosis of
      G1 tumors, is definitely characterized by a relative low sensitivity. The low
      sensitivity and subjective interpretation of cytology led to the development of
      several tests to detect bladder cancer in urine. We provide a current,
      comprehensive review of the literature on bladder tumor markers and summarize
      their diagnostic potential. In conclusion, under the premise that cystoscopy has
      never been subjected to evaluation, no diagnostic marker with a sensitivity and
      specificity comparable to cystoscopy currently exists. The combined analysis of
      several tumor markers, as in the Immunocyt test, seems to be the most promising
      approach. In the future, rather highly sensitive tests may be able to replace
      cystoscopy or prolong the intervals of cystoscopies in the follow-up of selected
      patients.

PMID- 11464030
TI  - Cytokeratin-20 reverse-transcriptase polymerase chain reaction as a new tool for
      the detection of circulating tumor cells in peripheral blood and bone marrow of
      bladder cancer patients.
AB  - OBJECTIVES: Systemic progression is the prevalent form of bladder tumor
      recurrence after radical cystectomy. The ability to detect circulating tumor
      cells in peripheral blood or bone marrow could be of prognostic value for the
      disease with the consequence of early adjuvant chemotherapy. We established a
      sensitive and specific method using a double cytokeratin-20 (CK-20) reverse
      transcriptase polymerase chain reaction (RT-PCR) to detect circulating bladder
      cancer cells in venous blood and bone marrow MATERIAL AND METHODS: The
      sensitivity of the detection method was determined by a serial dilution of
      bladder cancer cells from the cell line HT1376 in whole blood. Bone marrow from
      20 bladder cancer patients was drawn prior to radical cystectomy and CK-20 cDNA
      was amplified by RT-PCR. Additionally, pre- and postoperative venous blood
      samples from 11 of these patients with bone marrow aspirates and 9 patients
      undergoing only transurethral resection of the bladder as well as blood samples
      of 25 healthy volunteers were investigated by CK-20 RT-PCR. RESULTS: The
      detection limit of the method was 2 bladder cancer cells/ml whole blood
      containing one million peripheral blood mononuclear cells. The positive detection
      rate in bone marrow was 7 of 20 (35%) for bladder cancer patients of all stages.
      However, investigation of the preoperatively collected venous blood samples from
      20 patients revealed onyl 2 positive findings, belonging to advanced tumor stages
      pT4pN0M0 and pT3pN2M0. In contrast, CK-20 was detected in 3 of 20 postoperatively
      collected venous blood samples from patients with low tumor stages (pTaNXM0 and
      pT1NXM0) as well as from 1 patient with pelvic lymph node metastases (pT3apN2M0).
      All venous blood samples of the control group (n = 25) were negative for CK-20.
      CONCLUSION: The detection of circulating bladder tumor cells in venous blood and
      bone marrow by the CK-20 RT-PCR is a promising approach that could improve risk
      assessment and the identification of bladder cancer patients who would benefit
      from adjuvant chemotherapy.

PMID- 11464031
TI  - Activation of natural killer cells by Bacillus Calmette-Guerin.
AB  - OBJECTIVES: Using a human in vitro model we have previously identified so-called
      bacillus Calmette-Guerin (BCG)-activated killer (BAK) cells as potential effector
      cells in BCG immunotherapy. This study was designed to prove the hypothesis that
      BAK cells are a subpopulation of natural killer (NK) cells and to analyze the
      role of NK cells during BCG immunotherapy in vivo. METHODS: After stimulation of
      mononuclear cells (MNCs) with BCG for 7 days CD3+ and CD56+ lymphocytes were
      depleted by magnetic cell separation. Subsequently, the cytotoxicity of the
      marker-negative cell population was tested in a radioactive release assay.
      Coexpression of CD56/CD16 and CD56/perforin was assessed by flow cytometry. The
      importance of NK cells for effective BCG immunotherapy in vivo was analyzed by
      comparing BCG treatment of bladder tumors bearing 'wild-type' C57BL/6 and NK
      deficient beige mice. RESULTS: BAK cells were shown to have a CD3-/CD56+ NK cell
      phenotype. They expressed high amounts of perforin and low amounts of CD16, both
      of which are characteristic features of (activated) NK cells. BCG immunotherapy
      significantly prolonged survival in tumor-bearing C57BL/6 mice but was
      ineffective in NK-deficient beige mice. However, BCG treatment did not influence
      the frequency of pulmonary metastases in both mouse strains. CONCLUSIONS: Our
      data clearly indicate that stimulation of human MNCs with BCG leads to the
      activation of cytotoxic lymphocytes with NK cell phenotype. These killer cells
      express perforin and CD16, two molecules involved in NK cell cytotoxicity.
      Finally, ineffective BCG treatment of beige mice suggests a key role for NK cells
      during BCG immunotherapy in vivo.

PMID- 11464032
TI  - Radical cystectomy in patients older than 75 years: assessment of morbidity and
      mortality.
AB  - OBJECTIVE: We have reviewed our surgical experience to assess intra- and
      postoperative morbidity and mortality in 25 patients 75 years old or older with
      invasive bladder cancer who underwent radical cystectomy and urinary diversion or
      bladder substitution. METHODS: Between January 1993 and February 1999, of 190
      patients who underwent radical cystectomy, 23 men and 2 women were aged from 75
      to 87 (median 79) years. Urinary diversion was performed in 23 cases and bladder
      substitution in 2. All patients had significant comorbidity and 15 patients were
      ASA II and 10 ASA III. RESULTS: Median operating time was 4 h. Perioperative
      mortality rate was 4%. Intraoperative, early and late postoperative complications
      occurred in 15, 16 and 6 patients, respectively. The most common early
      complications were pyelonephritis (32%), disorientation (20%), additional
      pulmonary infection (20%) and prolonged ileus (32%). No secondary procedures were
      necessary. The most common late complication was ureteroileal anastomotic
      stricture (16%). The median hospital stay and intensive care unit stay were 24
      and 14 days, respectively. With a median follow-up of 14 (5-50) months the
      overall mortality rate was 32%. CONCLUSIONS: Radical cystectomy can be performed
      in elderly patients with acceptable perioperative mortality and morbidity.
      However, because of the high incidence of minor medical complications, hospital
      stay is often prolonged.

PMID- 11464033
TI  - Prediction of postoperative prostatic cancer stage on the basis of systematic
      biopsies using two types of artificial neural networks.
AB  - OBJECTIVE: The choice of therapy for prostatic cancer should depend on a rational
      preoperative estimate of tumor stage. Artificial neural networks were used to
      predict postoperative staging of prostatic cancer from sextant biopsies and
      routinely available preoperative data. METHODS: In group I (97 cases), nonorgan
      confinement (tumor stage > or =pT3a) was predicted on the basis of age and six
      histopathological variables from sextant biopsies. In group II (77 cases),
      nonorgan confinement and extraprostatic organ infiltration (tumor classification
      > or =pT3b) were predicted from age, four histopathological variables, the
      preoperative PSA level, and the total prostate volume estimated by preoperative
      ultrasonography. Learning vector quantization (LVQ) networks were applied for
      this purpose and compared to multilayer perceptrons (MLP) and linear discriminant
      analysis (LDA). RESULTS: Nonorgan confinement could be predicted correctly in 90%
      of newly presented cases from sextant biopsy histopathology alone. A similar
      accuracy of predicting nonorgan confinement (83%) was obtained by combining
      preoperative biopsy histology with clinical data. Extraprostatic organ
      infiltration could be predicted correctly in 82%. The best results were obtained
      by LVQ networks, followed by MLP networks and LDA. CONCLUSION: The postoperative
      tumor stage of prostatic cancer can be estimated with high accuracy, sensitivity
      and specificity from preoperative routine parameters using artificial neural
      networks, especially LVQ networks. The results suggest that this methodology
      should be evaluated in a larger prospective study.

PMID- 11464034
TI  - Prostate-specific antigen (PSA) value change after antibacterial therapy of
      prostate inflammation, as a diagnostic method for prostate cancer screening in
      cases of PSA value within 4-10 ng/ml and nonsuspicious results of digital rectal
      examination.
AB  - OBJECTIVES: Investigation of the possibilities of improving the accuracy of
      prostate cancer (PC) screening among patients with a PSA value of 4-10 ng/ml and
      nonsuspicious results of digital rectal examination (DRE), using as diagnostic
      method the PSA value change (PSA-VCh) after antibacterial treatment of prostate
      inflammation. METHODS: The study included 61 patients with PSA 4-10 ng/ml,
      nonsuspicious DRE and inflammation in expressed prostate secretion (EPS). All
      these patients underwent antibacterial therapy with the following repeated PSA
      determination and PSA-VCh assessment. RESULTS: Antibacterial therapy led to PSA
      decrease in 80% of cases. Effectiveness of PSA-VCh in PC screening was estimated.
      Sensitivity of PSA-VCh (with cut-off point -0.1.100%) equaled 85%, specificity
      96%, positive predictive value 85% and negative predictive value 96%.
      CONCLUSIONS: Prostate inflammation proves to be a significant factor contributing
      to serum PSA elevation up to 10 ng/ml among patients with nonsuspicious DRE.
      Assessment of PSA-VCh after antibacterial treatment can improve PC screening
      accuracy in cases of PSA 4-10 ng/ml, nonsuspicious DRE and inflammation in EPS.

PMID- 11464035
TI  - Transurethral holmium: YAG laser prostatectomy using a side-firing fiber for
      bladder outlet obstruction due to benign prostatic enlargement: urodynamic
      evaluation of surgical outcome.
AB  - OBJECTIVES: To prospectively assess the efficacy of transurethral holmium
      (Ho):YAG laser prostatectomy using a side-firing fiber in patients with bladder
      outlet obstruction due to benign prostatic enlargement (BPE) from the standpoint
      of urodynamics. METHODS: 32 male patients with BPE aged 53-83 (mean 69.4) years
      were operated on. All patients, excluding 3 with urinary retention, were
      evaluated with the International Prostatic Symptom Score (IPSS), Quality of Life
      (QOL) score and uroflowmetry up to 12 months postoperatively, and a pressure/flow
      study was performed before and 3 months after the operation. RESULTS: The total
      IPSS score, QOL score, average and maximum flow rates improved significantly
      (p<0.0001) at 12 months postoperatively. In the pressure/flow study, detrusor
      opening pressure, maximum detrusor pressure, detrusor pressure at maximum flow,
      minimum urethral opening pressure, and Abrams-Griffiths number decreased
      significantly (p<0.0001, p = 0.0001, p<0.0001, p = 0.0019 and p<0.0001,
      respectively) 3 months postoperatively. Detrusor instability disappeared in 12 of
      17 patients and remained in 2. CONCLUSIONS: Transurethral Ho:YAG laser
      prostatectomy was found to be effective for the treatment of bladder outlet
      obstruction due to BPE.

PMID- 11464036
TI  - Is transurethral vaporesection of the prostate better than standard transurethral
      resection?
AB  - OBJECTIVE: The aim of this study was to undertake an evaluation of the
      comparative efficacy and morbidity of transurethral vaporesection (TUVRP) and
      standard transurethral resection (TURP), two resection techniques using loops of
      different thickness and power settings. METHODS: In a prospective study, 185
      patients with lower urinary tract symptoms suggestive of bladder outlet
      obstruction and benign prostatic enlargement were randomized to undergo either
      TUVRP or standard TURP. Inclusion criteria were benign prostatic enlargement,
      moderate or severe lower urinary tract symptoms and/or a significant urinary
      residual (>60 ml), while patients with previous prostatic surgery, prostate
      cancer or neurogenic bladder disorders were excluded. Prostate size, residual
      urine, urinary flow rate and symptoms as well as associated bother (using the
      International Prostate Symptom Score (IPSS) and the American Urological
      Association Bother Score (AUA-BS)) were assessed preoperatively. Intraoperative
      blood loss and fluid absorption were evaluated by measuring serum hemoglobin and
      respiratory alcohol concentration. Patients were followed for 1 year with the
      evaluation of flow rates, residual urine volumes, symptom scores and
      complications at 3, 6 and 12 months. RESULTS: A significant difference was seen
      in the weight of the resected tissue (TURP 30.3 g vs. TUVRP 21.9 g, p<0.003).
      There were no significant differences in blood loss, intraoperative fluid
      absorption or procedure time between TUVRP and TURP, although more patients in
      the TURP group required blood transfusions (13 vs. 7) and mean procedure time was
      longer for TUVRP (71.0 vs. 65.9 min). The postoperative improvements in IPSS, AUA
      BS, residual and Q(max) were significant in both groups (p<0.01 for each) but
      without difference between the two groups. The rate of complications (urinary
      tract infections, urethral stricture, reintervention rate) during follow-up was
      the same in both groups. CONCLUSIONS: In this prospective randomized comparison
      of the clinical outcome and morbidity of standard TURP versus TUVRP, there were
      no significant differences in any of the parameters evaluated except for the
      weight of the resected tissue.

PMID- 11464037
TI  - Double-blind, crossover comparison of 3 mg apomorphine SL with placebo and with 4
      mg apomorphine SL in male erectile dysfunction.
AB  - OBJECTIVE: To establish the efficacy and safety of a fixed, 3-mg dose of
      apomorphine SL compared with placebo, and to compare 3 mg with 4 mg apomorphine
      SL in patients with erectile dysfunction. METHODS: This randomized, double-blind,
      crossover study included 296 heterosexual men with ED of various etiologies and
      severities. Two crossover groups were evaluated separately: 3 mg apomorphine SL
      vs. placebo (n = 194), and 3 vs. 4 mg apomorphine SL (n = 102). The primary
      efficacy variable was the percentage of attempts resulting in erections firm
      enough for intercourse; additional variables included the percentage of attempts
      resulting in intercourse and time to erection. Partner assessments were also
      analyzed. RESULTS: 3 mg apomorphine SL was significantly more effective than
      placebo (p<0.001) for the percentage of attempts resulting in erections firm
      enough for intercourse and resulting in intercourse, as assessed by both patients
      and partners. Median time to erection was 18.8 min. The 3-mg dose was not
      significantly different from 4 mg in the evaluation of efficacy variables, but
      the incidence of adverse events was higher with 4 mg. Nausea was the most common
      event, reported by 3.3% of patients on 3 mg vs. 14.1% on 4 mg; in the placebo
      comparison, nausea was reported by 7.0% of patients taking 3 mg apomorphine SL
      vs. 1.1% of those taking placebo. CONCLUSIONS: 3 mg apomorphine SL was
      significantly more effective than placebo and comparable to 4 mg, while offering
      an improved risk-benefit ratio.

PMID- 11464038
TI  - Risk factors for urinary incontinence in both sexes. Analysis of a health
      screening project.
AB  - PURPOSE: The aim of this study was to identify factors related to urinary
      incontinence in both sexes by analysing almost 2.500 individuals participating in
      a health screening project in the area of Vienna. MATERIALS AND METHODS: An
      incontinence questionnaire (Bristol LUTS questionnaire) was included to health
      investigations. During this investigation (a) a medical history; (b) a physical
      investigation; (c) sociodemographic parameters including smoking, eating and
      drinking habits, and (d) urine and blood study including 14 parameters were
      obtained. The parameters collected during this health investigation were
      correlated to the presence of urinary incontinence to identify potential risk
      factors for urinary incontinence. RESULTS: 1,262 women (49.7+/-13.6 years) and
      1,236 men (48.6+/-13.0 years) were analyzed. In the female population, 26.3%
      reported on episodes of urinary incontinence during the past 4 weeks. Among other
      factors, age (correlation coefficient [r] = 0.22), body mass index (r = 0.20),
      urgency (r = 0.16), feeling of incomplete bladder emptying (r = 0.21), previous
      uro-gynecological surgery and fasting blood glucose correlated significantly to
      urinary incontinence. Five percent of men were incontinent, age (r = 0.12),
      urgency (r = 0.16), nocturia (r = 0.16), feeling of incomplete emptying (r =
      0.16), reduced uroflow (r = 0.18) and previous prostatectomy (r = 0.11)
      correlated to the presence of urinary incontinence. In both sexes, smoking habits
      and the education level revealed no association. CONCLUSIONS: The high prevalence
      of urinary incontinence, its socioeconomic implications, the continuously ageing
      population and the fact that a number of potential risk factors, particularly in
      women, have been identified suggest that targeted prevention is a major task for
      the future.

PMID- 11464039
TI  - Storage detrusor pressure in bilateral hydroureteronephrosis.
AB  - OBJECTIVES: To determine the detrusor pressure (P(det)) during the storage phase
      associated with upper urinary tract (UUT) dilatation. SUBJECTS AND METHODS:
      Twenty-seven patients with bilateral hydroureteronephrosis, neither due to
      organic obstruction nor vesicoureteral reflux, were included. Water cystometry
      was done according to the recommendations of the International Continence Society
      [Abrams P., et al.: Scand J Urol Nephrol 1988(suppl 114):5-19]. P(det) at 25, 50,
      75 and 100% of bladder capacity was determined using the tag function of a
      computerized urodynamic system. RESULTS: The age of the patients ranged from 16
      to 81 years; 3 were females and 6 had renal insufficiency. In these 27 patients,
      high P(det) >15 cm H2O was sustained throughout the storage phase in only 11% of
      patients, and at 50 and 75% of bladder capacity in 44 and 88% of patients. About
      half (13/27) of the patients had a P(det) <40 cm H(2)O at capacity. Patients with
      renal insufficiency had a mean P(det) higher and more sustained over the storage
      phase compared to patients with normal renal function. The mean P(det) at all
      measured bladder volumes was significantly higher than in a control group of
      patients without hydroureteronephrosis. CONCLUSION: A P(det) >15 cm H(2)O but not
      necessarily 40 cm H2O, sustained for part of the storage phase but not
      necessarily throughout the whole storage phase, was associated with UUT
      deterioration. A higher and more sustained P(det) during the storage phase was
      associated with renal insufficiency.

PMID- 11464040
TI  - Double-J ureteral stents: an alternative to external urinary stents in orthotopic
      bladder substitution.
AB  - OBJECTIVE: The aim of this study was to compare advantages and disadvantages of
      using double-J or external stents to preserve the uretero-ileal anastomosis in
      patients receiving an orthotopic neobladder. METHODS: 77 consecutive patients
      with bladder cancer who underwent radical cystoprostatectomy and Studer
      neobladder were evaluated. All patients received a direct spatulated end-to-side
      uretero-ileal anastomosis in the afferent loop (Nesbit technique). In 45 patients
      (group A), the stents (Bracci ureteral splint) were brought our through the
      reservoir and anchored to the skin; in 32 patients (group B), an internal double
      J stent was used. Median follow-up was 30 months. RESULTS: 9 (11.5%) uretero
      ileal anastomosis strictures in group A and 7 (11.6%) in group B were observed.
      There was a significant difference in the side of stricture with a greater
      prevalence on the left side (p<0.004). Stricture formation and side were not
      related to the type of stent used. 14 (20%) neobladder-ureteral refluxes
      occurred, with a non-significant difference between the two groups (p = 0.37). 12
      patients (86%) were asymptomatic; two patients developed pyelonephritis and
      needed antibiotic treatment. Neobladder catheter was removed after 17 days
      (range: 15-18 days) and 14 days (range: 12-15 days), respectively, in group A and
      group B with an earlier discharge of the patients in group B. There was a
      significant difference in mean hospital stay between the two groups (Mann-Whitney
      test p<0.0001). Discomfort related to the stent was mild for most of the patients
      of group B (84%). CONCLUSIONS: Internal stenting is an equally effective
      alternative to external stent in patients undergoing bladder replacement. The use
      of double-j stents appears to be associated with minimal discomfort, earlier
      mobilization and a shorter hospital stay.

PMID- 11464041
TI  - Effects of eicosapentaenoic acid on urinary calcium excretion in calcium stone
      formers.
AB  - OBJECTIVES: The low incidence of atherosclerosis and other degenerative disease,
      including urolithiasis, in the Greenland Eskimo has been attributed to their high
      consumption of oily fish with its high concentration of eicosapentaenoic acid
      (EPA). With a westernized diet, the oxygenated products of renal prostaglandin
      synthesis are metabolites of the n-6 series and these are known to play important
      roles in several pathophysiological processes involved in calcium stone
      formation. Buck's group presented a hypothesis that the initiating factor for
      lithiasis triggers prostaglandin synthesis, and showed that this influenced by
      EPA treatment. METHOD: In order to ascertain the effects of EPA on plasma lipids
      and urinary parameters, we undertook a clinical study whereby a highly purified
      preparation was administrated (1,800 mg/day) to 88 patients with urinary stones
      for 3 months (short term) and 18 months (long term). RESULTS: Hyperlipemia
      improved the affected individuals and urinary calcium was significantly reduced
      in the hypercalciuric but not in the normocalciuric group. CONCLUSION: The
      results suggest that EPA by reducing urinary calcium might favorably affect urine
      composition in a way that possibly reduces the risk of calcium stone formation.

PMID- 11464042
TI  - Citric acid (solution R) irrigation in the treatment of refractory infection
      (struvite) stone disease: is it useful?
AB  - OBJECTIVE: Citric acid, in varying concentrations, has been used in the
      dissolution treatment of struvite renal calculi. Solution R (Uro-trainer), which
      contains 6% citric acid, is a solution licensed for use in the management of
      struvite stone disease in the UK. We report our experience. METHODS: 23 kidneys
      in 22 patients (10 male and 12 female patients, mean age 45, range 15-60 years)
      underwent solution R irrigation following debulking of the stone with
      percutaneous nephrolithotomy (n = 20), ureteroscopy and shock wave lithotripsy (n
      = 2) combined with open procedures (n = 4) between 1994 and 1998. The original
      stone configuration consisted of 14 staghorn, 4 partial staghorn and 5 large
      burden stones. Irrigation was performed through a nephrostomy tube (n = 20) or in
      a retrograde fashion (n = 3) using a closed infusion pump system (40 ml/h). The
      response to treatment was checked using a nephrostogram and/or plain X-ray.
      RESULTS: In 6 (26%) kidneys, after an average duration of 2 (1-5) days,
      irrigation had to be abandoned due to loin pain, leak or sepsis. The average
      duration of irrigation was 6.4 (1-20) days. At the end of irrigation, a total of
      4 (17.4%) kidneys had complete radiographic clearance, while the stone was
      reduced to calyceal dust in 3 (13%). Partial response was seen in 11 (47.8%) and
      no response in 5 (21.8%) kidneys. Following additional alternative
      intervention(s) in 6 (26%) kidneys (4 with partial and 2 with no response)
      further clearance was achieved in 3 (13%) and calyceal dust status in 3 (13%).
      The response was better if the stone was reduced to less than 10mm prior to
      irrigation. At the mean follow-up of 2.44 (1-4) years, of 13 kidneys with stone
      clearance or calyceal dust, 9 suffered recurrence or re-growth, 5 of which
      required further interventions. Only 4 (17.4%) of 23 kidneys remained stone free.
      CONCLUSIONS: In patients with complex stone disease, adjuvant solution R
      irrigation can reduce the stone burden. There is a considerable potential for
      side effects necessitating close monitoring for sepsis and electrolyte
      abnormalities. However, the overall success rate for solution R is limited.

PMID- 11464043
TI  - Extracorporeal shock wave lithotripsy in children. Efficacy, complications and
      long-term follow-up.
AB  - OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) is effective and safe
      for the treatment of upper urinary tract calculi in adults. Some speculations
      concerning possible damages from ESWL on the growing kidney have been raised.
      METHODS: From January 1990 to December 1998, 64 children (30 girls and 34 boys; 8
      months to 15 years old, mean 5.6 years) with a total of 83 stones of the upper
      urinary tract were treated by ESWL (Lithostar). Preoperative evaluation included
      history, physical examination, routine blood tests, urinalysis, urine culture,
      intravenous urography and optional renal scintigraphy. The impulse rate per
      treatment varied from 750 to 4,000 (mean 2,996). After acute treatment, routine
      follow-up included renal ultrasound, blood pressure controls, laboratory tests
      and eventually plain film X-ray. RESULTS: Successful fragmentation of the stones
      was achieved in all patients. In 54% the patients were free of stones treated at
      the time of discharge. At 3 months after treatment radiographic studies showed no
      residual fragments in 80% of the treated children. 83% of the treated stones were
      cleared entirely. The remaining fragments were clinically insignificant. An
      average of 2.5 ESWL treatments per child in general anesthesia were required.
      Stone analysis showed 20 calcium oxalate, 38 calcium phosphate, 12 struvite, 2
      uric acid and 9 cystine calculi. Ureteral stents were placed in 43%. No
      significant urinary infection was seen under antibiotic prophylaxis. Only 3
      children showed a recurrence (1 x cystinuria with low compliance and 2 x
      struvite). There was no case of renal scarring. No change in renal function or
      blood pressure was found compared to the preoperative values. Hematuria and
      proteinuria disappeared in all children who were free of stones. Renal ultrasound
      revealed no growth difference between treated and untreated renal units.
      CONCLUSIONS: In childhood, ESWL is an efficacious and safe treatment of stones of
      the upper urinary tract. The long-term follow-up after ESWL with a second
      generation lithotriptor did not show any signs of damage to the growing kidney.
      Sometimes repeated ESWL treatments are justified by the low rate of
      complications.

PMID- 11464044
TI  - Urological complications in pediatric renal transplantation.
AB  - OBJECTIVE: In this study, we evaluated the urological complications and their
      consequences after renal transplantation in children. MATERIALS AND METHODS: A
      retrospective study was performed concerning urological complications after
      kidney transplantation in children at the University Medical Center St Radboud
      Nijmegen from August 1977 until July 1999. The mean age of the cadaver kidney
      donors was 23.2 (range 1-74.3) years. RESULTS: In this period 146 children
      received 183 renal allografts. Twenty-four urological complications (13.1%) were
      noted in 23 patients. Urinary leakage was seen in 8 cases (4.4%) and a ureteral
      stenosis was present in 7 cases (3.8%), 5 patients developed stones (2.7%) and 4
      severe lymph leakage needing surgical treatment (2.2%). In 3 patients the
      urological complication induced graft loss. In cadaver kidneys from donors
      younger than 5 years there was no significantly increased complication rate in
      comparison to older cadaver kidneys [2/32 (6.3%) versus 16/125 (12.2%)]. In a
      subgroup of 24 patients treated for severe posterior urethral valves the
      complication rate was not significantly increased in comparison to the others
      (8.3% in the group with posterior urethral valves against 13.7% in the group
      without). CONCLUSIONS: Urological complications are a small threat for graft
      function and the results are comparable with earlier studies. Routine ultrasound
      can be important for early detection of problems in the postoperative period. A
      close observation in the postoperative care and good collaboration between
      pediatric nephrologist and urologist is mandatory. Sometimes, early intervention
      can be undertaken with the possibility of saving graft function and reducing
      morbidity.

PMID- 11464045
TI  - Intestinal perforation as a complication of tension-free vaginal tape procedure
      for urinary incontinence.
AB  - OBJECTIVES: To report and prevent a serious complication of tension-free vaginal
      tape (TVT) procedure. CASE REPORT: One day after a TVT procedure, an emergency CT
      scan showed adhesion of intestinal loops with a pneumoperitoneum. The patient had
      previously had intra- and retroperitoneal surgery with a sacral cervicopexy and a
      Burch colposuspension. CONCLUSION: In such a case of previous surgery, a CT scan
      may be useful before a TVT procedure.

PMID- 11464046
TI  - Acute renal failure due to rhabdomyolysis associated with radical perineal
      prostatectomy.
AB  - We report a case of acute renal failure due rhabdomyolysis as a result of the
      exaggerated lithotomy position during radical perineal prostatectomy. The
      pathogenesis, diagnosis, management, and preventive measures of acute renal
      failure associated with rhabdomyolysis are also reviewed.

PMID- 11464047
TI  - Transient paralysis of the bladder due to wound botulism.
AB  - In the last 10 years, wound botulism has increasingly been reported and nearly
      all of these new cases have occurred in injecting-drug abusers. After absorption
      into the bloodstream, botulinum toxin binds irreversibly to the presynaptic nerve
      endings, where it inhibits the release of acetylcholine. Diplopia, blurred
      vision, dysarthria, dysphagia, respiratory failure and paresis of the limbs are
      common symptoms of this intoxication. Surprisingly and despite the well-known
      blocking action of the botulinum toxin on the autonomic nerve system, little
      attention has been paid to changes in the lower urinary tract following acute
      botulinum toxin poisoning. Here we report a case of bladder paralysis following
      wound botulism. Early diagnosis and adequate management of bladder paralysis
      following botulism is mandatory to avoid urologic complications. Accordingly, the
      prognosis is usually favorable and the bladder recovery complete.

PMID- 11464048
TI  - Metastatic primitive neuroectodermal tumor of the kidney in adults.
AB  - OBJECTIVE: Primitive neuroectodermal tumors (PNET) of the kidney are rare and
      highly aggressive malignancies. The purpose of our study was to present
      information about the management of patients with metastatic disease. METHODS:
      The records of 2 patients (30-year-old female and 32-year-old male) with
      metastatic PNET of the kidney were reviewed and our data compared with the
      literature. RESULTS: Neither clinical evaluation nor radiological methods allowed
      to distinguish PNET from renal cell carcinoma. Immunohistochemistry revealed
      strong positivity for CD99 in tumor 1 and weak positivity for NSE and vimentin in
      both tumors. In tumor 2, EWS/FLI1 translocation was detected by RT-PCR. Patient 1
      underwent nephrectomy, seven cycles of polychemotherapy, two cycles of high-dose
      chemotherapy, autologous bone marrow rescue, radiotherapy of suspicious skeletal
      foci and is without evidence of recurrent disease 28 months after therapy.
      Patient 2 underwent six cycles of polychemotherapy, nephrectomy, high-dose
      chemotherapy with cyclophosphamide and abdominal radiotherapy. Because of relapse
      high-dose chemotherapy with stem cell rescue was not performed. He underwent
      three further cycles of polychemotherapy and died one year after diagnosis due to
      cerebral metastasis. CONCLUSIONS: The diagnosis of renal PNET must be considered
      in young patients with renal neoplasm, particularly those with advanced disease
      at presentation. Achieving exact diagnosis has important clinical consequences
      because polychemotherapy and high-dose chemotherapy may lead to dramatic tumor
      reduction or even complete remission.

PMID- 11464050
TI  - The early detection and diagnosis of bladder cancer: a critical review of the
      options.
AB  - Bladder cancer has a high worldwide incidence matched by a tendency to recur,
      necessitating close and regular follow-up. Current methods of investigation of
      bladder cancer involve cystoscopy, ultrasound scanning and contrast urography,
      with additional information provided by cytology. These methods, although having
      a high detection rate, are expensive, time-consuming, invasive and uncomfortable.
      There is, therefore, a need for an inexpensive, noninvasive, quick and simple
      investigation with a high sensitivity and specificity for the detection of
      bladder cancer. There are an increasing number of molecular assays available for
      the detection of bladder cancer. From bladder tumour antigens to nuclear matrix
      proteins to adhesion molecules, cytoskeletal proteins and growth factors, urology
      has looked at them all to support the early detection and diagnosis of bladder
      cancer. This review critically discusses both the commercial as well as the
      research-based diagnostic assays available (their mode of action, overall
      accuracy - both by stage and grade, and their uses and limitations from both a
      clinical as well as a practical point of view). Aiming to give an insight into
      the options currently available for noninvasive bladder cancer diagnosis, it also
      provides prospective comment on what new methods/technologies may be useful in
      the medium term.

PMID- 11464051
TI  - Metastatic urothelial cancer: evaluation of prognostic factors and change in
      prognosis during the last twenty years.
AB  - OBJECTIVE: This study was designed to establish prognostic factors for survival
      of patients with locally advanced or metastatic urothelial cancer. We have
      furthermore investigated changes in patient characteristics and treatment
      strategies during the last 20 years. PATIENTS AND METHODS: Between 1992 and 1997,
      a total of 156 patients with newly diagnosed recurrent locally advanced disease
      (nonresectable, radioresistant) and/or metastatic transitional cell carcinoma of
      the urothelial tract were included in a protocol evaluating clinical and
      laboratory prognostic factors at baseline. The relationship between these
      characteristics and survival was analyzed using univariate and multivariate
      methods. The results were compared to the survival results of similar patients
      treated previously from 1976 to 1991. RESULTS: Median survival after diagnosis of
      recurrent locally advanced or metastatic disease was 5.8 months. Multivariate
      analysis showed that good performance status (PS), normal alkaline phosphatase
      (AP), absence of liver metastases and chemotherapy were independent prognostic
      factors for long survival. An increase in survival was found when comparison was
      made with 240 patients treated in the period from 1976 to 1991, but the period of
      treatment had no independent importance in multivariate analysis. CONCLUSION: PS,
      AP and liver metastases are the major important prognostic factors in metastatic
      urothelial cancer. Stage migration and increased use of chemotherapy may have
      contributed to improved median survival during the last 20 years.

PMID- 11464052
TI  - The use of valrubicin for the chemoresection of superficial bladder cancer -- a
      marker lesion study.
AB  - OBJECTIVES: To assess the effect and tolerance of a 6-week course of intravesical
      valrubicin on a tumour intentionally left in the bladder (marker lesion)
      following incomplete transurethral resection of the bladder (TURBT). PATIENTS AND
      METHODS: In a prospective phase II study, 40 patients with refractory superficial
      transitional cell carcinoma (TCC), with or without carcinoma in situ, underwent
      TURBT at which a tumour <1 cm in diameter was deliberately left in the bladder.
      They were then treated with six instillations of 800 mg valrubicin at weekly
      intervals. Patients were assessed three months after the initial TURBT by
      cystoscopy and biopsy. Patients remaining clear of disease underwent repeat
      cystoscopies at 3-monthly intervals until recurrence or for up 2 years. RESULTS:
      21/39 (54%) of patients were found to be clinically clear of disease upon
      cystoscopic examination at 3 months. 18/39 (46%) of patients were considered
      histologically clear of bladder disease. The current estimate of the mean time to
      recurrence is 248 days. CONCLUSIONS: A 6-week course of intravesical valrubicin
      has proved effective in ablating a marker tumour left in the bladder after
      incomplete TURBT and in preventing or delaying recurrence of further tumours in a
      group of patients with previously treated superficial TCC.

PMID- 11464053
TI  - Correlation of positive prostate sextant biopsy locations to sites of positive
      surgical margins in radical prostatectomy specimens.
AB  - OBJECTIVE: To investigate whether sextant location of positive prostate biopsy
      predicts the site of positive surgical margins (PSM) at the time of radical
      prostatectomy (RP) in patients with clinical stage T1c prostate cancer. METHODS:
      A retrospective query of the Center for Prostate Disease Research (CPDR) database
      at our institution identified 456 patients with clinical stage T1c prostate
      cancer who underwent standard sextant prostate biopsy prior to RP. Each biopsy
      was submitted separately for pathologic analysis according to sextant location.
      The sextant location of positive biopsies was compared to the sites of PSM after
      RP. RESULTS: PSM were found in 129 of 456 (28%) RP specimens. The incidence of
      PSM at the prostate apex in patients with a positive or negative apical sextant
      biopsy was similar (9 and 8% respectively, p>0.05). The incidence of PSM at the
      prostate base in patients with a positive or negative sextant biopsy of the
      prostate base was also the same (7% in both groups, p>0.05). As the number of
      positive biopsy cores on one side of the prostate increased (0, 1, 2, and 3) so
      did the chance of an ipsilateral PSM (5.4, 16.2, 35.7 and 45.0%, respectively;
      p<0.005). CONCLUSIONS: Positive sextant biopsy location (apex and base) does not
      correlate with site of PSM at RP. However, ipsilateral PSM are more likely as the
      number of positive sextant biopsies on that side increases. While pathologic
      processing of biopsy specimens according to longitudinal prostate location (base,
      mid and apex) is probably unnecessary, the number of positive biopsies on a given
      side may be useful preoperative information.

PMID- 11464054
TI  - Outcome of laterally directed sextant biopsies of the prostate in screened males
      aged 50--66 years. Implications for sampling order.
AB  - OBJECTIVE: Prostate cancer has its most frequent location in the posterior
      lateral part of the gland. The aim of this study was to evaluate the cancer
      detection rate of six systemic prostate biopsies with mid lobar biopsies taken
      far laterally in the prostate. PATIENTS AND METHODS: A total of 692 patients
      (aged 50--66 years) enrolled in a screening study underwent prostate biopsies
      because of an elevated serum prostate-specific antigen (PSA; > or =3 ng/ml)
      level. The outcome of the biopsies was related to findings at digital rectal
      examination (DRE) and transrectal ultrasound (TRUS) and to the location within
      the prostate. RESULTS: Prostate cancer was detected in 164 patients. DRE and TRUS
      were suspicious of malignancy in 66 cases (40%) and 84 cases (51%), respectively.
      The two biopsies taken far laterally midlobar in the prostate detected as many as
      83% of the cancers and when combined with two apical biopsies, 96% of all cancers
      were detected. CONCLUSION: At PSA screening in this age-group, only 57% of the
      prostate cancers detectable by sextant biopsies were palpable or visible at TRUS.
      Most of the cancers (96%) were detectable by only four systematic, carefully
      directed biopsies. In men with normal DRE, the two lateral midlobar biopsies
      should be taken first during the biopsy procedure.

PMID- 11464055
TI  - Spatial distribution of prostate cancers undetected on initial needle biopsies.
AB  - OBJECTIVES: The spatial distribution of cancer foci of prostate carcinomas with
      negative initial biopsies was compared to that of prostate carcinomas with
      positive initial biopsies to detect areas in which carcinomas were more
      frequently located when the initial biopsy was negative. METHODS: Twenty patients
      with prostate cancer and a negative initial biopsy trial were detected among 218
      patients with preceding systematic biopsies (9.2%) in our hospital. Analysis of
      the prostatectomy specimens regarding cancer distribution, multifocality, tumour
      size, Gleason score, and stage was performed using pathohistological techniques
      and three-dimensional computer reconstruction. RESULTS: Prostatectomy specimens
      with negative initial biopsies showed more frequently cancer foci in apical
      (p<0.0001) and dorsal (p<0.02) prostatic compartments, higher incidence of
      multifocality (p<0.01), and smaller size of carcinoma foci (p<0.00003) compared
      to carcinomas in 81 stage-matched prostatectomy specimens with positive initial
      biopsies. Comparing both groups, no significant differences were noted in Gleason
      score of preoperative biopsies and prostatectomies, prostate weight, prostate
      specific antigen (PSA) level, digital rectal examination, and patients age.
      CONCLUSIONS: Missing the cancer in clinically significant prostate carcinomas by
      current systematic biopsy techniques may also be due to an apico-dorsal cancer
      location, particularly in combination with multifocality and small size of
      carcinoma foci in large prostates. In case of reasonable clinical suspicion of
      prostate cancer and negative initial biopsy, an early repeat biopsy with special
      emphasis on the apico-dorsal peripheral zone should be envisaged.

PMID- 11464056
TI  - Renal cell carcinoma: evaluation of the 1997 TNM system and recommendations for
      follow-up after surgery.
AB  - OBJECTIVE: We evaluated the tumor recurrence pattern after radical or nephron
      sparing surgery for localized renal cell carcinoma. Based on this pattern, we
      suggest a surveillance protocol after surgery. METHODS: The outcome of 200
      consecutive patients with localized renal cell carcinoma (RCC) that were operated
      on between January 1982 and December 1997 was evaluated retrospectively. Radical
      nephrectomy was performed in 155 patients (77.5%), and nephron-sparing surgery in
      45 patients (22.5%). The timing and site of disease recurrence were correlated
      with parameters of the primary tumor. RESULTS: One hundred and twenty-four
      patients (62%) had pathological stage T1, 26 (13%) had stage T2, and 50 (25%) had
      stage T3 (41 stage T3a, 8 stage T3b, and 1 stage T3c). The mean follow-up was 47
      months (range 6--169 months). Four patients (3.2%) with stage T1, 6 patients
      (23%) with T2, and 13 patients (26%) with T3 developed recurrent disease. None of
      the patients with a stage T1 tumor, smaller than 4 cm, had tumor recurrence.
      There were no recurrences after nephron-sparing surgery compared to 23
      recurrences (14.8%) among patients after radical nephrectomy (p = 0.01). Only 1
      patient who underwent pulmonary lobectomy for asymptomatic metastases smaller
      than 2.5 cm, found by routine chest CT, attained long-term survival. CONCLUSIONS:
      The prognosis of patients after radical nephrectomy for renal cell carcinoma,
      smaller than 4 cm, is excellent and they do not need radiological follow-up.
      Patients with larger T1 tumors, 4--7 cm in diameter, or a higher stage should be
      followed with CT of the chest and abdomen done every 6 months for 5 years and
      then annually. Following partial nephrectomy of small renal tumors periodic renal
      ultrasonography should be done to rule out local recurrence in the operated
      kidney.

PMID- 11464057
TI  - Coagulating intermittent cutting. Improved high-frequency surgery in
      transurethral prostatectomy.
AB  - OBJECTIVES: Transurethral prostatectomy (TURP) is the gold standard in surgical
      therapy of symptomatic bladder outlet obstruction. TURP is characterised by
      immediate treatment success, due to the removal of obstruction combined with a
      long-lasting improvement of symptoms and voiding parameters. In spite of good
      long-term results of TURP, intraoperative blood loss produces morbidity. We
      investigated a blood-sparing cut using a new high-frequency technology. METHODS:
      (1) A standard high frequency generator was extended in its function by
      additional electronics. (2) The possibility of a blood-sparing cut using
      'coagulating intermittent cutting' (CIC cocut BMP) was quantified ex vivo using a
      blood-perfused porcine kidney. Four cuts next to each other were performed
      through the parenchyma using a standard resectoscope with a standard loop. This
      was done with a commercially available generator and CIC cocut BMP. The blood
      loss was determined semiqantitatively. RESULTS: (1) In a first step 'coagulating
      cutting' with coagulating and cutting periods (10/94-- 08/96) was developed.
      During each cut, phases with predominant cutting effect alternate with
      coagulating phases of defined duration. As a disadvantage, operation time
      increased due to lower cutting speed. In a second step cutting combined with
      coagulation effect with high voltage pulses -- 'coagulating intermittent cutting'
      (08/96--06/97) -- was developed. In this technique, the output signal consists of
      a pulse-modulated sinusoidal voltage with high amplitudes. But gas bubbles
      impaired vision. This finally resulted in the 'coagulating intermittent cutting'
      with constant voltage pulses and control of pulse intervals (CIC cocut BMP, since
      07/97 up to now). (2) Comparing the function of the high-frequency generators in
      vitro, the Wilcoxon test for paired samples revealed a significant reduction of
      the observed bleeding with the CIC cocut BMP (p = 0.002). CONCLUSIONS:
      'Coagulating intermittent cutting' improves the gold standard of TURP with
      reduced blood loss. The procedure is feasible with a standard resection
      equipment. The already trained surgeon has no further learning cure, and teaching
      of classical TURP is maintained.

PMID- 11464058
TI  - Male lower urinary tract symptoms and related health care seeking in Germany.
AB  - OBJECTIVES: To investigate the prevalence of lower urinary tract symptoms (LUTS)
      and LUTS- related health care issues in the male population between the ages of
      50 and 80 in Germany. METHODS: 8,973 randomly chosen men in the age group of
      interest received by mail a self-administered questionnaire addressing voiding
      symptoms and bother, common health status, and social demographic as well as
      health care resources related issues. RESULTS: Of 6,031 (67.2%) returned
      questionnaires, 5,404 (60.2%) were properly filled out and entered into the
      database. Of these, 5,004 (56%) completed all IPSS questions. 3,539 (70.7%) of
      the men presented with no or mild LUTS (IPSS 0--7), 1,465 (29,3%) with moderate
      to severe voiding symptoms (IPSS >7), respectively. From logistic regression
      analysis it appears that mainly bother from voiding symptoms as well as
      incomplete emptying and week stream induced a visit to the doctor. Of men with
      moderate symptoms (IPSS 8--19), 40% did not report any bother. CONCLUSION: LUTS
      is a common condition among German elderly males. In general, bother from LUTS
      seem to have more effects on health care seeking behavior than symptoms
      themselves or physical health status. Bother scores may discriminate between
      those individuals with moderate symptoms (IPSS 8--19), who may be followed
      through watchful waiting instead of active therapy.

PMID- 11464059
TI  - Transurethral microwave thermotherapy for symptomatic benign prostatic
      hyperplasia: long-term durability with Prostcare.
AB  - OBJECTIVE: To evaluate the long-term durability of transurethral microwave
      thermotherapy (TUMT) with Prostcare for symptomatic benign prostatic hyperplasia
      (BPH). PATIENTS AND METHODS: From August 1993 to July 1994, a total of 65
      patients with symptomatic BPH who underwent TUMT using the Prostcare apparatus
      (Bruker Spectospin, Wissembourg, France) with low-energy protocol (maximal power
      52 W) were enrolled into a short-term evaluation. Subsequent follow-up
      information was collected in July 1999. If patients had had any further therapy
      for BPH, the date of retreatment was considered as an endpoint of TUMT efficacy.
      If no further therapy for BPH had been needed, they were re-assessed for overall
      satisfaction. RESULTS: The median follow-up period was 49 months. Twenty patients
      were excluded for various reasons, including 17 with loss of follow-up and 3 with
      new diseases that could affect the voiding status. Thirty-eight (84.4%) of 45
      valuable patients had received further therapy for BPH, including medication (n =
      21, 46.7%), and endoscopic surgery (n = 17, 37.7%). The times to pharmacologic or
      endoscopic retreatment after TUMT were 8.9+/-11.1 and 23.0+/-14.4 months,
      respectively (p = 0.0003, log rank test). Only 7 (15.5%) patients had no further
      treatment, with 3 having satisfactory improvements, but 4 feel dissatisfied yet
      not needing any further therapy. In addition, 2 patients complained of erectile
      dysfunction after TUMT and 1 was diagnosed with prostate cancer 50 months after
      TUMT. In addition, there was no significant difference for all baseline values
      among three groups with no retreatment or retreatment with medication or
      endoscopic surgery. CONCLUSION: At the 5-year follow-up, the long-term durability
      of low-energy TUMT with Prostcare is only exhibited in a few patients and the
      overall retreatment rate was 84.4%. Thus, patient should be informed of the high
      probability of supplementary treatment after TUMT.

PMID- 11464060
TI  - Nephrostomy tube or 'JJ' ureteric stent in ureteric obstruction: assessment of
      patient perspectives using quality-of-life survey and utility analysis.
AB  - INTRODUCTION: Upper urinary tract obstruction is often relieved by either a
      percutaneous nephrostomy tube (PCN) or a ureteric stent. Both can cause
      considerable morbidity and reduce patient's health-related quality of life (QoL).
      We have compared the QoL in these 2 groups. PATIENTS AND METHODS: 34 patients (21
      stent and 13 PCN) with unilateral ureteric obstruction were prospectively
      studied. Each patient completed a questionnaire, which included a common single
      health index (EuroQol EQ-5D) and intervention-specific questions to assess pain,
      urinary symptoms and day-to-day problems. RESULTS: There were 22 male and 12
      female patients [mean age 56+/-9 years (PCN) and 55+/-14 years (stent)]. The mean
      duration between the intervention and conduct of the survey was 12+/-5 days for
      PCN and 28+/-14 days for stent. There was no different in the mean EuroQol score
      (p = 0.199) and analogue score (p = 0.596) indicating no differences in the gross
      defects in physical and psychosocial function and the utility between the 2
      groups. There was a significant difference in the urinary symptoms (p<0.0001)
      with patients who had a stent experiencing significantly more irritative urinary
      symptoms. This group also suffered discomfort for a greater duration and in
      various postures requiring more analgesia (although not significant with
      Bonferroni correction). Patients with PCN required more help in the daily care of
      the nephrostomy tube. There was no difference in the incidence of infections and
      the need for antibiotics. CONCLUSIONS: Patients with 'JJ' stents have
      significantly more irritative urinary symptoms and a high chance of local
      discomfort than patients with nephrostomy tubes (PCN). However, based on the
      EuroQol analysis, there is no significant difference in the gross impact on the
      health-related QoL or the utility between these groups indicating no patient
      preference for either modality of treatment.

PMID- 11464061
TI  - Outpatient holmium laser lithotripsy using semirigid ureteroscope. Is the
      treatment outcome affected by stone load?
AB  - OBJECTIVES: To compare the outcome of outpatient ureteroscopic laser lithotripsy
      (URSL) for ureteral stone larger than 10 mm in longest diameter (group 1) with
      those less than or equal to 10 mm (group 2). METHODS: 134 patients with solitary
      ureteral stone were treated by outpatient URSL. No exclusion criteria with
      regards to stone size, level or composition were applied. Semirigid ureteroscopy
      and holmium-YAG laser lithotripsy was performed under general anaesthesia as
      outpatient procedure. Radiological follow-up by intravenous urogram was performed
      3 months postoperatively. Patients' demographic data, stone parameters, operative
      details and treatment outcome were collected prospectively and compared between
      the two groups. RESULTS: Among the 134 ureteral stones, 41(31%) were larger than
      10 mm. Group 1 contained more upper and middle ureteral stones than group 2 (68
      vs. 40% p = 0.001). Operating time was significantly longer for group 1 (68.9 vs.
      46.8 min, p<0.001) and postoperative stenting rate was higher (83 vs. 60%, p =
      0.01). There was no difference between the groups in terms of 3 months stone
      clearance rate (92.7 vs. 91.4%, p = 0.8). Complication rate was higher in group 1
      (22 vs. 5.4%, p = 0.004) especially for lower stones (46.2 vs. 5.4%, p = 0.001)
      but most of which were minor complications that were treated conservatively. One
      patient in group 1 (2.4%) developed ureteral stricture at the longstanding stone
      impaction site despite postoperative stenting. The stricture resolved subsequent
      to balloon dilatation. CONCLUSIONS: URSL can treat stones larger than 10 mm in
      longest diameter at all levels safely and effectively in an outpatient setting.

PMID- 11464062
TI  - The tension-free transvaginal tape procedure in the treatment of female urinary
      stress incontinence: a French prospective multicentre study.
AB  - OBJECTIVE: To evaluate in a prospective multicentre study (five centres) the
      preliminary results regarding efficacy and morbidity of the new tension-free
      transvaginal tape (TVT) technique in the treatment of urinary stress incontinence
      (USI) in women. METHODS: From November 1996 to May 1999, 52 women of mean age 64
      (range 37--91) years underwent the TVT procedure to treat isolated grade 2 or 3
      USI (44 cases) or grade 1 or 2 USI associated with uterine or rectal prolapse
      surgery (8 cases). Twenty-nine patients (55.8%) presented recurrent USI (1--4
      previous procedures). Clinical data showed urethrovesical junction hypermobility
      in 35 cases (67.3%), isolated intrinsic sphincter deficiency (ISD) in 17 cases
      (32.6%) and pelvic organ prolapse in 8 cases. Urodynamics confirmed ISD in 27
      cases (51.9%) with a mean urethral closure pressure of 18.5 (range 7--25) cm
      H(2)O. All data were collected by surgeons on a questionnaire. RESULTS: The
      surgical procedure was performed under spinal cord anaesthesia in 82.7% of
      patients (local anaesthesia 11.5%) with a mean operation time of 30 (range 20-
      60) min for TVT implantation. Six bladder injuries (11.5%) were identified and
      the needle was repositioned. Mean hospital stay was 2.5 (range 1-7) days in the
      group who underwent TVT alone. Mean follow-up of continence was 15.2 (range 6-
      36) months: 83% of patients were dry and 17% were improved. Nine patients (17.3%)
      required self-catheterization for 2--10 days postoperatively. No recurrence of
      USI, defect healing or tape rejection were reported. CONCLUSION: TVT is a new
      technique for the surgical treatment of USI which is useful for recurrent cases.
      The advantages are simplicity, low morbidity, reproducibility and reduced
      operative time. These early results indicate the technique is effective in
      correcting incontinence and is locally well tolerated. But these are preliminary
      data and the long-term outcome on USI and the urethra is needed.

PMID- 11464063
TI  - Calcitonin receptor gene polymorphism: a possible genetic marker for patients
      with calcium oxalate stones.
AB  - OBJECTIVES: The formation of urinary stones is hypothesized to be associated with
      calcitonin receptors. The most commonly seen polymorphism is C/T at the 1377th
      nucleotide. Hence, these polymorphisms are being used as a genetic marker in the
      search for the cause of urolithiasis. METHODS: A normal control group of 105
      healthy people and 102 patients with recurrent calcium oxalate stones were
      examined. The polymorphism was detected following a polymerase chain reaction
      based and restriction analysis by AluI. An uncuttable length is 228 bp (CC)
      whereas two fragments of 120 and 108 bp are shown as cuttable lengths (TT).
      RESULTS: The results revealed significant differences between the normal
      individuals and the stone patients (p<0.01). The distribution of leucine
      (cuttable) homozygote in the stone group (2.0%) was higher than in the control
      group (0.0%). The odds ratio for the leucine allele of the calcitonin receptor
      gene in calcium oxalate stone disease is 5.634 (95% CI: 2.286--13.885).
      CONCLUSIONS: Results show that the polymorphism in the calcitonin receptor gene
      could be a genetic marker for urinary stone disease and therefore it is
      worthwhile pursuing further studies of the leucine allele of calcitonin receptor
      gene due to it is strongly correlated with stone disease.

PMID- 11464064
TI  - Erectile dysfunction in cyclists. Is there any difference in penile blood flow
      during cycling in an upright versus a reclining position?
AB  - OBJECTIVE: Perineal compression during bicycling appears to be responsible for
      some cases of erectile dysfunction. MATERIAL AND METHODS: In 46 healthy athletic
      men transcutaneous penile oxygen pressure (tpO(2)) at the glands of the penis was
      measured, using a transcutaneous measurement device. It has been shown that the
      tpO(2) levels measured at the glans correlate with the penile blood flow. Our
      measurements were performed before, during and after cycling in an upright and a
      reclining position in a crossover study. RESULTS: The mean transcutaneous pO(2)
      at the glans in a standing position before biking was 60.5+/-8.1 mm Hg. It
      decreased after sitting on the saddle in an upright position to 17.9+/-3.9 mm Hg.
      Continued cycling in a seated upright position showed pO(2) levels of 18.3+/-5.2
      mm Hg, with a full return to normal pO(2) values after a 10-min recovery period
      in a standing position. Cycling in a reclining position resulted in pO(2) levels
      of 59.4+/-4.2 mm Hg, a similar level to that obtained before exercising.
      CONCLUSIONS: The results of the present study demonstrated that there is a
      deficiency in penile perfusion caused by perineal arterial compression. Cycling
      in a reclining position - in which no perineal compression was seen - caused no
      alteration in penile blood flow during exercising. Therefore, we suggest cycling
      in a reclining position to avoid health hazards - such as penile numbness and
      hypoxygenation of the corpora cavernosa, which can result in impotency.

PMID- 11464066
TI  - Subcortical brain mechanisms in speech and language.
AB  - This paper reviews current research and contemporary theories of subcortical
      participation in the motor control of speech production and language processing.
      As a necessary precursor to the discussion of the functional roles of the basal
      ganglia and thalamus, the neuroanatomy of the basal ganglial-thalamocortical
      circuitry is described. Contemporary models of hypokinetic and hyperkinetic
      movement disorders based on recent neuroanatomical descriptions of the multi
      segmented circuits that characterise basal ganglion anatomy are described.
      Reported effects of surgically induced lesions in the globus pallidus and
      thalamus on speech production are reviewed. In addition, contemporary models
      proposed to explain the possible contribution of various subcortical structures
      to language processing are described and discussed in the context of evidence
      gained from observation of the effects of circumscribed surgically induced
      lesions in the basal ganglia and thalamus on language function. The potential of
      studies based on examination of the speech/language outcomes of patients
      undergoing pallidotomy and thalamotomy to further inform the debate relating to
      the role of subcortical structures in speech motor control and language
      processing is highlighted.

PMID- 11464067
TI  - The aging voice: a review, treatment data and familial and genetic perspectives.
AB  - This paper will provide a review of aspects of vocal aging within the context of
      general body aging and describe two data sets related to the aging voice. Data
      will be presented which document pre- to posttreatment improvement in select
      voice characteristics (sound pressure level, subglottal air pressure,
      thyroarytenoid laryngeal muscle activity and voice quality) following application
      of an intensive voice treatment program (the LSVT) to 3 individuals with aged
      voice. Additionally, physiological data (forced expiratory volume, visual
      accommodation, bone density, taste discrimination, white blood count and resting
      heart rate) and select perceptual (perceived age) and acoustic measures
      (reflecting both cycle-to-cycle and longer-term intensity and frequency
      stability) from 67 subjects will be reviewed from the work of Gray and colleagues
      to document the differential impact of the global aging process across organ
      systems including the aging voice.

PMID- 11464068
TI  - Psychosocial aspects of aphasia: whose perspectives?
AB  - This paper reviews some different meanings of the term 'psychosocial' and
      identifies the different ways in which the social and psychological sequelae of
      aphasia can be explored. These include qualitative methods, which seem well
      suited to addressing such complex issues. Having outlined some features of
      qualitative research, the paper describes a study in which fifty people talked
      about the consequences and significance of their long-term aphasia. Their
      'insider perspective' on aphasia suggests its impacts are extensive, complex,
      direct and indirect, interconnected, systemic, dynamic and diversely experienced.
      The paper discusses the various implications of the study for clinicians and
      researchers concerned with the psychosocial aspects of aphasia and outlines how
      some of the issues raised in the interviews might be addressed.

PMID- 11464069
TI  - Effects of atropine and propranolol on retinal vessel diameters during isometric
      exercise.
AB  - PURPOSE: There is controversy regarding the nervous control of retinal blood
      vessels in humans. Most in vitro studies indicate that the intraocular part of
      the central retinal artery lacks autonomic innervation. We investigated the
      response of retinal vessels to isometric exercise during blockade of beta
      receptors (propranolol) or muscarinic receptors (atropine). METHODS: Twelve
      healthy subjects performed squatting for 6 min during infusion of either
      propranolol atropine or placebo. Blood pressure and pulse rate were measured non
      invasively. Retinal vessel diameters were measured continuously using the Zeiss
      Retinal Vessel Analyser. RESULTS: Squatting induced a significant increase in
      blood pressure and pulse rate, which was paralleled by a decrease in retinal vein
      and artery diameters. Atropine did not change the retinal vessel response to
      isometric exercise. Propranolol significantly blunted the exercise-induced
      vasoconstriction in retinal arteries. CONCLUSION: This result likely indicates
      propranolol-evoked vasoconstriction in the extraocular parts of the central
      retinal artery during isometric exercise.

PMID- 11464070
TI  - Protective effect of docosahexaenoic acid against retinal ischemic injury: an
      electroretinographic study.
AB  - PURPOSE: To determine whether docosahexaenoic acid (DHA) can reduce the retinal
      damage induced by transient retinal ischemia. METHODS: Retinal ischemia was
      induced by increasing intraocular pressure (IOP). Retinal circulation was
      restored by lowering IOP. An intraperitoneal injection of 1,000 mg/kg of DHA
      ester (DHA-E) was given 5 h before the ischemia. Electroretinograms were recorded
      just before the ischemia and at 60-min intervals up to 4 h after circulation was
      restored. RESULTS: The ratio of the amplitudes after the ischemia to that just
      before ischemia was significantly higher in eyes administered DHA-E than in
      controls at each time point (p < 0.01). CONCLUSION: DHA-E is effective in
      protecting the retina against transient retinal ischemia.

PMID- 11464071
TI  - Involvement of oxygen free radicals in experimental retinal ischemia and the
      selective vulnerability of retinal damage.
AB  - Protective effects of CV-3611, a free radical scavenger, on retinal ischemic
      injury in the rat and on glutamate-induced cytotoxicity in a cell line were
      evaluated. Transient retinal ischemia was induced by raising intraocular pressure
      of rats to 110 mm Hg for 45 min, and the electroretinogram (ERG) was measured to
      evaluate retinal function. No ERG could be recorded immediately after
      reperfusion, and thereafter the ERG gradually recovered. Recovery of the a-wave
      latency and the amplitudes of the a and b waves in the CV-3611-treated (10 mg/kg,
      p.o.) group were significantly better than those in the control group up to 24 h
      after reperfusion. In both the control and CV-3611 group, the b wave showed
      better recovery than the a wave up to 6 h after reperfusion, while the
      relationship was reversed after 24-hour reperfusion. Glutamate (10 mM)-induced
      cytotoxicity in the N18-RE-105 cell, a neural retina-neuroblastoma hybridoma, was
      quantified by measuring lactate dehydrogenase. Three and 10 microM of CV-3611
      significantly attenuated the glutamate-induced cytotoxicity in N18-RE-105 cells.
      Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function
      after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity.
      These results suggest that oxygen free radicals play an important role in the
      early phase of retinal ischemic injury. Moreover, differential recovery processes
      of the a and b waves after ischemia suggest that the selective vulnerability of
      the retina to ischemia could change functionally during the period of
      reperfusion.

PMID- 11464072
TI  - Photoreceptor protection against constant light-induced damage by isopropyl
      unoprostone, a prostaglandin F(2alpha) metabolite-related compound.
AB  - Some of the antiglaucoma drugs have shown neuroprotective effects in ischemic
      retinal damage and optic nerve injury. We studied photoreceptor protection
      against constant light-induced damage using isopropyl unoprostone, a
      prostaglandin F(2alpha) metabolite-related compound. Albino Sprague-Dawley rats
      were administered isopropyl unoprostone solution intravitreally in one eye (the
      test eye) and vehicle alone in the contralateral eye (the control eye) and were
      exposed to constant light for 7 days. Histological examinations were performed to
      evaluate photoreceptor protection by quantifying the outer nuclear layer (ONL)
      thickness and scoring the rescue of ONL. Seven-day constant light affected
      photoreceptors and produced a marked disruption of photoreceptor outer segments
      and inner segments and a decrease in the thickness of the ONL. As compared with
      control eyes, pretreatment by intravitreal administration of isopropyl
      unoprostone 2 days prior to constant light exposure provided protection from the
      light insult, and the effects of rescue were dependent on the dose of the agent
      (0.6-6.0 microg), the maximum dose protecting about 70% of the photoreceptors.
      Topical application of the drug had little rescue effect. Aberrant macrophages in
      light-exposed eyes with unoprostone injection were more numerous than in normal
      eyes, but the extent did not differ significantly from that of degenerated eyes
      injected with vehicle only. Isopropyl unoprostone has shown protection of
      photoreceptors against constant light-induced damage, and it is thus suggested
      that the agent has neuroprotective activity in vivo.

PMID- 11464073
TI  - Specific labeling of lens aldehyde dehydrogenase class 1 from (3)H-cholesterol or
      its derivatives.
AB  - We investigated the possibility that sterols could covalently modify ocular lens
      cell proteins. Incubation of cultured bovine lens epithelial cells (BLEC) with
      (3)H-cholesterol led to the labeling of a cytosolic protein of about 52 kD. Two
      dimensional electrophoresis of the BLEC soluble proteins and fluorography
      revealed one labeled protein of 52 kD, pI = 6.6, plus a weakly labeled, slightly
      more acidic protein of the same size. MALDI-MS analysis of both proteins
      recovered from duplicate gels indicated both to be aldehyde dehydrogenase class 1
      (ALDH-1). The identity was confirmed by immunoprecipitation with antiserum to
      ALDH-1. Alkaline hydrolysis of (3)H-labeled ALDH-1 released most of the
      radiolabel as compounds much more polar than cholesterol. We speculate that lens
      ALDH-1 can participate in the oxidation of cholesterol or its derivatives to
      unidentified sterol carboxylic acids and that the labeled protein reflects
      capture of ALDH-1 with sterol intermediates covalently bound to the enzyme in
      ester linkage. Lens ALDH-1 might, therefore, participate in the detoxication of
      polar sterols.

PMID- 11464074
TI  - Interaction between delta-9-tetrahydrocannabinol and indomethacin.
AB  - The effect of indomethacin on the Delta9-tetrahydrocannabinol (Delta9-THC)
      induced fall in rabbit intraocular pressure (IOP) was determined. A 2% suspension
      of indomethacin was given topically 1 h before intravenous injection of Delta9
      THC. IOP was measured hourly and was compared between groups receiving either
      Delta9-THC alone or Delta9-THC plus indomethacin. A substantial attenuation of
      the IOP response to Delta9-THC was caused by indomethacin. Delta9-THC may
      influence IOP at least in part by a prostaglandin-mediated process. Involvement
      of the cyclooxygenase pathway offers a common explanation for linking several
      ocular cannabinoid effects. The latter include a fall in IOP, conjunctival
      hyperemia and minor inflammation.

PMID- 11464075
TI  - Dryness symptoms, diagnostic protocol and therapeutic management: a report on
      1,200 patients.
AB  - PURPOSE: To report the diagnostic and therapeutic data obtained from 1,200
      patients suffering from dry eye symptoms not due to Sjogren's syndrome or other
      auto-immune diseases. METHODS: Schirmer test I, ferning test, breakup time, vital
      dye staining, brush and imprint cytology were performed; data were grouped into
      diagnostic profiles, and the therapy was prescribed according to these. RESULTS:
      Eight diagnostic profiles were identified. Dry eye was diagnosed in 57.1% of
      patients; the remaining 42.9% were found to suffer from eye discomfort or
      conjunctivitis of different aetiologies. CONCLUSIONS: Subjective symptoms of
      dryness can hide diseases other than dry eye; combined clinical and laboratory
      tests are requested to make a diagnosis. Our experience indicates that a therapy
      prescribed on the basis of diagnostic profiles provides relief in 79.1% of cases.

PMID- 11464076
TI  - Experimental intravitreal application of trovafloxacin in rabbits.
AB  - This study was performed to examine the retinal toxicity of trovafloxacin, a
      broad-spectrum fourth-generation fluoroquinolone, in rabbit eyes after
      intravitreal injection. The left eyes of 20 albino rabbits were divided into four
      groups, and each was injected intravitreally with 0.1 ml of trovafloxacin in a 50
      microg, 100-microg, 250-microg or 500-microg concentration. The right eyes of
      these rabbits served as control and received normal saline solution. Retinal
      function was assessed from the electroretinogram (ERG), and retinal structure was
      also examined by ophthalmoscopy and histologic study (light microscopy). The
      intravitreal injections of 50 microg, 100 microg, and 250 microg trovafloxacin
      did not significantly change the ERG a-wave, b-wave or the oscillatory potential
      throughout the follow-up period of 4 weeks. While no ERG changes were observed at
      4 weeks after injection, in the 3 eyes that received trovaloxacin 500 microg/0.1
      ml, the a-wave amplitudes showed a diminution of 56-49% and those of b-waves one
      of 53-44% of the preinjection amplitudes at 4 weeks after injection, but
      oscillatory potentials remained unchanged in the other 2 rabbits intravitreally
      injected with 500 microg trovafloxacin. However, in none of the injected eyes and
      the control eyes in all groups were ophthalmoscopically visible fundus changes
      and histologic abnormality observed. The results suggest that intravitreally
      injected trovafloxacin at a dose of up to 500 microg is nontoxic to the rabbit
      retina. If future studies in other species confirm our findings, intravitreal
      trovafloxacin may be a good alternative in the treatment and prevention of
      clinical bacterial endophthalmitis.

PMID- 11464077
TI  - Management of COPD: surgical options.
AB  - Dyspnoea on exertion and exercise intolerance are the hallmarks of chronic
      obstructive pulmonary disease (COPD); the primary causes appear to be
      respectively, increased airway resistance with reduced maximal ventilatory
      capacity and peripheral skeletal muscle dysfunction with early onset of anaerobic
      metabolism. Patients with end-stage COPD usually show little or no benefit from
      conventional medical treatment. Physical training is capable of ameliorating
      exercise tolerance, but improvement is usually modest in the advanced disease
      state. Two surgical options are generally accepted for carefully selected
      patients with emphysema: resection of large bullae, when identified, and lung
      transplantation. Transplantation, the only effective cure for advanced COPD, is
      of limited use primarily because of age, comorbidity, limited availability of
      organs and cost. A different approach for severe emphysema, lung volume reduction
      surgery (LVRS), has been increasingly utilized during the past several years. In
      carefully selected emphysematous patients, LVRS improves lung volumes and
      mechanics, and reduces exertional dyspnoea. Unfortunately, surgical mortality
      still remains high and some patients show no measurable improvement after
      surgery. There is an urgent need for data on long-term effects of LVRS; the
      results of large, randomized trials will soon be forthcoming. The aim of this
      brief review is to summarize the available knowledge on the effects of LVRS, the
      criteria for patient selection, short- versus long-term effects and, finally, to
      propose future directions in this field.

PMID- 11464078
TI  - Drug-induced bronchospasm--a negligible phenomenon?

PMID- 11464079
TI  - Drug-induced bronchospasm: analysis of 187 spontaneously reported cases.
AB  - BACKGROUND: The Swiss Drug Monitoring Center (SANZ) uses a systematic approach to
      the collection of spontaneously reported individual cases on suspected adverse
      drug reactions (ADRs). Spontaneous reporting schemes are designed to detect new,
      rare and unexpected ADRs and to act as an early warning system but there is a
      tendency to overreport severe reactions. OBJECTIVES: The aim of the study was to
      determine drug-induced episodes of bronchospasm, their seriousness and
      predisposing risk factors. An ADR is classified as serious if the reaction
      results in death, is life-threatening, requires inpatient hospitalization or
      prolongation of existing hospitalization, results in persistent or significant
      disability or incapacity. RESULTS: From 1986 to 1995 SANZ received 8,191 case
      reports of suspected ADRs. In 187 cases (2%) bronchospasm was reported. In 55% of
      these cases the reaction was regarded as serious. Analgesics and nonsteroidal
      anti-inflammatory drugs (NSAIDs) were reported most frequently and were involved
      in 24% of the cases of which 64.5% were classified as serious. In three cases a
      lethal outcome was reported after intravenous administration of metamizol. Anti
      infectious agents were implicated in 18% (52% serious), cardiovascular drugs in
      11% (50% serious), drug formulation agents in 9% (41% serious), vaccines and
      immunoglobulins in 5.5% (50% serious), and plasma volume expanders in 5.5% (80%
      serious). Other drug groups were involved in 27% of the cases. About 50% of
      patients experiencing bronchospasm after NSAIDs, pharmaceutical formulation
      agents, vaccines and immunoglobulins had predisposing risk factors such as
      asthma, atopy or drug allergy. In other drug groups a predisposing factor was
      identified in 27% or less. CONCLUSION: Drug-induced bronchospasm is frequently
      reported with NSAIDs, anti-infective agents, cardiovascular drugs and excipients
      with a high proportion of serious reactions.

PMID- 11464080
TI  - Prevalence of emphysema in individuals who underwent screening CT for lung cancer
      in Nagano prefecture of Japan.
AB  - BACKGROUND: Screening for lung cancer with low-dose spiral computed tomography
      (CT) was carried out in Nagano prefecture in Japan. OBJECTIVE: To study the
      prevalence of emphysema in 7,847 individuals based on the Nagano spiral CT
      screening and to correlate the prevalence and severity of emphysema with various
      factors. METHODS: Spiral CT images with scan parameters of 120 kV, 50 mA, 10-mm
      collimation and a pitch of 2 obtained at full inspiration were retrospectively
      evaluated in 7,847 individuals. Emphysema was defined as the presence of low
      attenuation areas in the lung parenchyma. Extent of emphysema was graded on a
      four-level scale and correlated with gender, age and smoking habits. RESULTS:
      There were 4,288 males and 3,559 females. Mean age of the subjects was 61 years;
      45.8% of the participants were smokers. Overall prevalence of emphysema was 2.9%;
      the prevalence was significantly higher in males (5.0%) than in females (0.5%);
      it was also significantly higher in smokers, and increased with age. Emphysema
      was positively correlated with age, but there was no correlation with smoking
      indices. Emphysema was mostly mild and localized in the upper lung. The logistic
      model revealed that gender, age and smoking indices were significant factors for
      developing emphysema. CONCLUSIONS: Overall prevalence of emphysema was 2.9%. The
      prevalence was higher in males and in older people. Smoking was also related to a
      higher prevalence of emphysema but not to its severity.

PMID- 11464081
TI  - Continuous positive airway pressure and lung inflation in sleep apnea patients.
AB  - BACKGROUND: It was shown in normals that an important decrease in upper airway
      resistance can be obtained with continuous positive airway pressure (CPAP). It
      was suggested that lung inflation in patients with sleep apnea syndrome (SAS)
      could also be a mechanism of action of CPAP. OBJECTIVE: In the present study we
      wanted to evaluate the effects of nocturnal CPAP on the daytime lung function
      pattern in patients with SAS. METHODS: We measured arterial blood gases and
      possible changes in static lung volumes in 57 SAS patients (37 with normal lung
      function, 10 with COPD and 10 with restrictive lung disease) after at least one
      month of CPAP therapy. RESULTS: A significant increase in PaO(2) (from 79 to 84
      mm Hg, p = 0.01) and a decrease in AaDO(2) (from 23 +/- 1 to 16 +/- 1, p < 0.01)
      was only observed in SAS patients with normal lung function. This improved gas
      exchange was parallelled by a small but non significant change in the FRC (from
      96.5 +/- 3.2 to 105.4 +/- 3.7%pred, p = 0.07) and TLC (from 101.3 +/- 1.7 to
      104.1 +/- 1.4%pred, p = 0.15). Similar changes in TLC and FRC were also observed
      in SAS patients with obstructive and restrictive lung disease. CONCLUSIONS:
      Chronic nocturnal CPAP therapy can improve daytime gas exchange and may influence
      lung inflation during the daytime. The small changes seem to be a functional
      effect but of no clinical relevance.

PMID- 11464082
TI  - Prevalence of habitual snoring in a sample of French males. Role of "minor" nose
      throat abnormalities.
AB  - BACKGROUND: No data on snoring prevalence obtained with a standard questionnaire
      exist for France. Major nose-throat abnormalities have been demonstrated in cases
      with obstructive sleep apnea; evidence of "minor" abnormalities in community
      studies is scarce. OBJECTIVES: The first objective of our study was to estimate
      the prevalence of habitual snoring in a sample of middle-aged active males in
      France. The second objective was to test the hypothesis that "minor" nose-throat
      abnormalities could be associated with habitual snoring in a field survey.
      METHODS: Three hundred thirty-four male employees of a local university
      volunteered for the study (93.6% of those contacted by mail); 300 returned a
      sleep questionnaire. The protocol also included anthropometry and a noninvasive
      nose-throat examination. RESULTS: Complete data were obtained in 299 subjects
      aged 23-63 years. When "habitual snorers" (= 32%) were compared with never
      snorers, significant differences were found for all anthropometric variables,
      except height. In univariate analysis, habitual snoring was associated with a
      large number of variables, including a large soft palate, a large uvula, and
      altered nose patency. A logistic regression model retained 8 factors
      independently associated with snoring: age, neck circumference, tobacco
      consumption, breathing pauses during sleep, not feeling rested during the day,
      need for coffee to stay awake, blocked or running nose at night and a large soft
      palate. CONCLUSIONS: The prevalence of habitual snoring in this sample of middle
      aged French males was 32%. We confirmed the significant association of habitual
      snoring with age, weight excess, and tobacco smoking, and identified two further
      factors: blocked nose at night and a large soft palate.

PMID- 11464083
TI  - Diagnostic value of D dimer in pulmonary embolism and pneumonia.
AB  - BACKGROUND: Diagnosis of pulmonary embolism (PE) and its clear-cut
      differentiation with other entities of occasional similar presentation remains
      difficult in routine clinical practice. High plasmatic levels of D dimer (DD), a
      specific fibrin derivate, have recently been reported in PE. OBJECTIVE: The
      purpose of this study was to prospectively evaluate the diagnostic value of
      plasmatic DD in a clinical setting. METHODS: We studied 52 patients with PE
      proven with pulmonary scintigraphic studies in relation to 19 patients
      posteriorly diagnosed of having community-acquired pneumonia and 30 healthy
      subjects. Evolution of DD levels whilst the patients were on intravenous
      anticoagulant therapy was evaluated by measuring DD concentration on admission
      and on day 7 in 10 patients. RESULTS: Plasma DD levels were significantly higher
      in PE in relation to controls (p < 0.001). DD levels were also higher in patients
      diagnosed with community-acquired pneumonia in relation to controls (p < 0.05)
      but lower than those obtained in high probability PE (p < 0.05). Sensitivity and
      specificity of plasmatic DD in the emergency diagnosis of PE are of 92 and 71%,
      respectively. Plasma levels of DD were found to progressively decrease during the
      first week of heparin therapy, but they remained higher than in control subjects.
      CONCLUSIONS: Plasma DD levels are increased in patients with suspected PE and the
      degree of elevation is related to the results obtained in scintiscans. Moreover,
      DD concentrations progressively decrease during the first week of anticoagulant
      therapy. The increased DD levels found in patients with pneumonia make this test
      useless in the differential diagnosis between these two clinical entities.

PMID- 11464084
TI  - Invasive thymoma: a clinical study of 23 cases.
AB  - BACKGROUND: Invasive thymoma is a rare mediastinal tumor. Clinicopathological
      characteristics that influence survival of patients with this tumor are under
      debate. Treatment is based on tumor resection. The benefice of therapies, such as
      radiation therapy (RT) and/or chemotherapy (CT) as adjuvant treatments to
      surgery, or palliative therapy to unresectable or recurrent thymoma are
      discussed. OBJECTIVES: The aim of this study was to assess patients with invasive
      thymoma, with specific emphasis on factors predicting survival. METHODS: We
      studied retrospectively 23 patients with invasive thymoma. Parameters assessed
      were age, presenting symptoms, histological features, stage at diagnosis,
      treatment modalities and survival. All patients received primary therapy: 11
      patients (48%) had tumor resection associated with CT and/or RT, while 12
      patients had palliative therapy including RT and/or CT. Regimens for CT were
      based on cisplatin. RESULTS: Patients' mean age was 58 years. Three patients had
      stage II disease at diagnosis (13%), 8 patients had stage III (35%) and 12
      patients had stage IV (52%). Median overall survival was 20 months (range: 4-160)
      and five-year survival rate was 43.5% (10 patients). Surgical resection had a
      significant impact on survival (p < 0.0001). Survival was also related to stage
      of the disease at diagnosis (p = 0.006), but not to histology of the tumor (p =
      0.12). Salvage treatment was of clinical importance: 5 out of 15 patients (33.3%)
      who relapsed during a 5-year follow-up responded to a multimodality therapeutic
      approach that affected survival (p = 0.019). CONCLUSION: Factors determining the
      outcome of these tumors are the stage of the disease at diagnosis, and the
      adequacy of surgical removal. Salvage treatment of recurrent thymoma may give a
      moderate response rate and improve survival.

PMID- 11464085
TI  - Pulmonary nocardiosis: clinical experience in ten cases.
AB  - BACKGROUND: Pulmonary nocardiosis is an infrequent infection whose incidence
      seems to be increasing due to a higher degree of clinical suspicion and the
      increasing number of immunosuppressive factors. OBJECTIVE: To study the
      predisposing factors, clinical characteristics, diagnostic procedures, treatment
      and progress of pulmonary nocardiosis (PN). METHODS: Review of 10 patients (9
      male, 1 female, mean age 61) with PN in a 600-bed teaching hospital, diagnosed
      from 1992 to 1999. RESULTS: Associated diseases observed were chronic obstructive
      pulmonary disease (COPD) in 6 patients, human immunodeficiency virus (HIV)
      infection in 3 and polymyalgia rheumatica in 1. Four patients had received oral
      corticotherapy for COPD for over a year (mean dose 13 mg/day of prednisone or
      equivalent). The main reason for consultation was an increase in dyspnea in the
      patients with COPD (6/6) and fever in those with HIV (3/3). Mean time between
      onset of symptoms and diagnosis was 5 weeks. In 8 patients, the infection
      occurred outside the hospital setting. The infection was restricted to the lung
      in 9/10; in the remaining case, the central nervous system (CNS) and subcutaneous
      tissue were affected. Lobar or multilobar consolidation was the most frequent
      radiographic pattern found (6/10). Sputum culture was positive when performed (8
      cases). Diagnosis was made or confirmed by bronchoscopy (bronchoaspirate or
      protected specimen brush) in 5 patients. Germs isolated were: Nocardia asteroides
      (8/10), Nocardia farcinica (1/10), Nocardia otitidiscaviarum (1/10).
      Cotrimoxazole was the most used empirical treatment (6/10). Resolution was
      achieved in 5 cases. Four subjects died: 1 HIV patient with disseminated
      nocardiosis, and 3 COPD patients, 2 of whom had received long-term
      corticotherapy. Illness recurred in only 1 case, due to failure to comply with
      treatment. CONCLUSIONS: (1) In our geographical setting Nocardia presents as a
      subacute or chronic pulmonary infection, mainly outside the hospital. (2) It
      tends to affect only the lung. (3) Diagnosis requires a high clinical suspicion,
      and can be made on the basis of a sputum culture. (4) Nocardia tends to attack
      patients with underlying COPD, or immunodepressed patients treated with
      glucocorticoids, or patients with HIV infection. (5) Mortality is high in both
      COPD and HIV patients. (6) In our area, cotrimoxazole seems to be the most
      commonly prescribed treatment.

PMID- 11464086
TI  - Increased interleukin-5 levels in bronchoalveolar lavage fluid is a major factor
      for eosinophil accumulation in acute eosinophilic pneumonia.
AB  - BACKGROUND: Increased interleukin-5 (IL-5) levels have been reported in
      bronchoalveolar lavage fluid (BALF) from patients with acute eosinophilic
      pneumonia (AEP); however, it still remains to be determined whether IL-5 is
      responsible for the eosinophil accumulation in the lung. OBJECTIVE: We examined
      the effect of antibodies against cytokines on eosinophil chemotaxis induced by
      BALF from AEP patients to identify factors responsible for eosinophil
      accumulation. METHODS: We measured a series of specific cytokines, including IL
      3, IL-4, IL-5, IL-6, IL-8, GM-CSF, RANTES, MCP-1, MIP-1alpha and eotaxin, in the
      BALF from 4 patients with AEP. BALF from 4 patients with chronic eosinophilic
      pneumonia (CEP) and 13 patients with non-eosinophilic interstitial lung diseases
      (ILD) were examined as controls. The eosinophil chemotactic activity in the BALF
      was examined using tissue culture insert furnished with a polycarbonate membrane.
      RESULTS: The total protein content in BALF from patients with AEP was extremely
      elevated. Even after standardization with protein concentration, IL-5 levels in
      AEP patients were significantly higher than those in CEP and ILD. IL-3 and
      chemokines were rather lower in the AEP group than in the CEP and ILD groups. In
      AEP BALF, anti-IL-5 neutralizing antibody significantly inhibited eosinophil
      chemotaxis. Antibodies against IL-3, GM-CSF, and IL-8 did not affect the
      eosinophil migration. CONCLUSION: These findings suggest that locally produced IL
      5 plays an important role in eosinophil accumulation of AEP.

PMID- 11464087
TI  - Quantification of the size of primary spontaneous pneumothorax: accuracy of the
      Light index.
AB  - BACKGROUND: The size of a pneumothorax (PTX) is usually estimated by the Light
      index. Treatment strategies of (primary, spontaneous) PTX partially depend upon
      the size of the PTX. To our knowledge, the Light index has not yet been
      correlated with the actual volume of the PTX. OBJECTIVES: To correlate the
      estimated size of a primary spontaneous PTX by means of the Light index, with the
      actual amount of air present in the pleural space. METHODS: Actual PTX volumes
      were measured by means of manual aspiration of air present in the pleural space
      in 18 patients with primary spontaneous PTX and correlated with the size
      estimation obtained by the Light index. RESULTS: Light index and volume
      measurements were strongly correlated (r = 0.84, p < 0.0001). CONCLUSIONS: The
      Light index is a good estimate of the actual size of a (primary spontaneous) PTX.

PMID- 11464088
TI  - Comparison of a new desktop spirometer (Diagnosa) with a laboratory spirometer.
AB  - BACKGROUND: The Diagnosa is a fully integrated system, able to determine
      spirometry, ECG, blood pressure and body composition. Real time data can be
      transferred via Internet to a remote receiving center. OBJECTIVES: The aim of
      this study was to perform biological testing of the spirometry component in
      subjects with normal and pathological pulmonary function. METHODS: A group of 45
      patients (mean age 43.3 years, 30 males) was tested on both the Diagnosa and the
      standard Jaeger Masterlab spirometer according to the guidelines of the American
      Thoracic Society. Three subgroups of 15 subjects each (normal spirometry,
      obstructive and restrictive airflow limitation) were selected. RESULTS: All
      measurements performed with the Diagnosa (FVC, FIVC, FEV(1), PEF, FEF(25),
      FEF(50), FEF(75)) correlated closely (r = 0.92-0.99) with those performed with
      the Jaeger spirometer and showed good limits of agreement (the largest difference
      between the two devices being 0.2 liter for FEV(1)). Analysis of the 3 subgroups
      showed no difference for any parameters compared to the overall group. Electronic
      transfer of all data was successful. CONCLUSIONS: The Diagnosa spirometer is
      comparable to a standard laboratory spirometer and can be used reliably for
      telemedicine purposes.

PMID- 11464089
TI  - Pushed, pulled or twisted?

PMID- 11464090
TI  - High-dose-rate endobronchial brachytherapy in endobronchial metastatic malignant
      chondroid syringoma.
AB  - A 65-year-old man with malignant chondroid syringoma (MCS) was found to have
      pulmonary metastases in the form of multiple pulmonary nodules 4 years after wide
      excision and adjuvant radiotherapy of a primary abdominal wall tumor. Atelectasis
      of the lingula due to obstructive endobronchial metastasis, resistant to
      combination chemotherapy, led us to perform high-dose rate (HDR) endobronchial
      brachytherapy for the first time in this rare tumor with a favorable response.
      This case emphasizes the role of HDR brachytherapy as a palliative procedure in
      endobronchial tumors not responding to other treatment modalities, even those
      considered to be radioresistant.

PMID- 11464091
TI  - Obstructive granulomatous bronchiolitis due to Mycobacterium avium complex in an
      immunocompetent man.
AB  - While the development of pulmonary disease due to Mycobacterium avium complex
      (MAC) infection is most commonly associated with underlying predisposing factors,
      this organism occasionally causes symptomatic disease in otherwise normal
      individuals. Patients with MAC pulmonary disease most often present with
      cavitating granulomas, but a spectrum of pathologic changes has been described.
      The authors present a case of MAC pulmonary disease in an immunocompetent, middle
      aged man with no identified predisposing factors. The diagnostic biopsy disclosed
      the unusual finding of noncaseating granulomas with predominant involvement of
      bronchioles, corresponding to the patient's obstructive and restrictive pulmonary
      dysfunction.

PMID- 11464092
TI  - Tetracycline aspiration. Case report and review of the literature.
AB  - A 74-year-old woman presented with a 2-day history of cough, dyspnea and wheezing
      following aspiration of a tetracycline tablet. She developed a left lower lobe
      pneumonitis, and bronchoscopy revealed left main bronchus narrowing and exudate.
      The course of this patient is discussed in reference to the available literature
      on toxic aspirations.

PMID- 11464093
TI  - Nearly fatal complications of cervical lymphadenitis following BCG immunotherapy
      for superficial bladder cancer.
AB  - This report describes the case of a 68-year-old man with bilateral cervical
      lymphadenitis and chorioretinitis due to bacille Calmette-Guerin (BCG),
      originating from BCG immunotherapy for treatment of superficial bladder cancer 2
      years ago. During antimycobacterial therapy a fistula between the right-sided
      lymph node and an aneurysm of the carotid artery developed. This led to life
      threatening spontaneous bleeding which required vascular graft surgery. Like
      other known systemic side effects, cervical lymphadenitis may also occur
      following intravesical BCG immunotherapy, and life-threatening complications
      cannot be excluded despite adequate medical treatment.

PMID- 11464094
TI  - Possible relevance of virus infection for development of analgesic idiosyncrasy.
AB  - Although it has been hypothesized that analgesic idiosyncrasy could be acquired
      by viral infection, there is no evidence that any virus can cause sporadic cases
      of aspirin-intolerant asthma. We report a case, which points to the possible
      relevance of herpes simplex virus (HSV) infection for development of analgesic
      idiosyncrasy. We examined the patient to evaluate whether analgesic idiosyncrasy
      might have been acquired by viral infection. Sulpyrine provocation testing was
      performed to confirm the patient's development of analgesic idiosyncrasy and
      methacholine provocation testing was performed to assess bronchial
      hyperresponsiveness. The titer of anti-HSV IgG antibody was measured to confirm
      viral infection. Sulpyrine provocation testing revealed that hypersensitivity to
      analgesics had appeared in this patient. In contrast, the marked improvement of
      her bronchial hyperresponsiveness was confirmed by a PC(20) methacholine of 0.63
      mg/ml 1 week after sulpyrine provocation testing. The anti-HSV IgG antibody
      confirmed recent HSV infection. To the best of our knowledge, this is the first
      reported case of acquired analgesic idiosyncrasy following HSV infection.

PMID- 11464095
TI  - Bronchiolitis obliterans with organizing pneumonia associated with acute Coxiella
      burnetii infection.
AB  - We report the case of a 62-year-old man who developed bronchiolitis obliterans
      with organizing pneumonia (BOOP) associated with acute Coxiella burnetii
      infection. The diagnosis of BOOP was made by fiber-optic transbronchial biopsy.
      Treatment with corticosteroids resulted in rapid clinical improvement and
      complete resolution of airspace opacities. To the best of our knowledge, this is
      the first well-documented case of BOOP associated with C. burnetii infection.
      This case suggests that this infection might trigger the development of BOOP.

PMID- 11464096
TI  - Cavitary opacity following lung transplantation.

PMID- 11464097
TI  - Is there a need for another inhalative beta(2)-agonist besides formoterol in
      patients with asthma?
AB  - Formoterol can substitute the rapid- and short-acting beta(2)-agonists as well as
      the slow- and long-acting salmeterol. Therefore formoterol in a fixed combination
      with an inhalant steroid reduces the aerosol devices necessary for asthma control
      to only one, to be used for regular "controller" and, as needed, "rescue
      therapy". The side effect profile of formoterol is comparable to the short-acting
      beta(2)-agonists which makes the combination with a topically active
      glucocorticoid applicable in patients of any asthma severity as long as they are
      able to perform an inspiratory vital capacity maneuver

PMID- 11464098
TI  - Serum CA19-9 levels reflect bronchoalveolar lavage fluid neutrophil levels in
      idiopathic pulmonary fibrosis.

PMID- 11464099
TI  - A case of parenchymal pulmonary endometriosis, diagnosed by cytologic examination
      of bronchial washing.

PMID- 11464100
TI  - Assessment of 'dry skin': current bioengineering methods and test designs.
AB  - Dry skin is a frequent problem in dermatology and a sign of dysfunction of the
      epidermis, especially of the stratum corneum as the morphological equivalent of
      the skin barrier. It may occur as an individual disposition or as the leading
      symptom of atopic dermatitis or ichthyosis. Besides the visual examination of the
      skin, various bioengineering methods have been developed to assess the different
      pathological and adaptive changes in the skin. In addition to the assessment of
      skin humidity, barrier function and desquamation, the quantification of skin
      surface topography and the mechanical properties of skin are suitable methods to
      characterize a dry skin condition. For clinical assessment of moisturizing
      products and emollients the parameters of investigation have to be defined and
      integrated in an adapted study design depending on the composition and content of
      the active agent in the test product. Newly developed cosmetic products have to
      be investigated for safety and efficacy. Modern bioengineering methods are
      suitable to fulfill these challenges.

PMID- 11464101
TI  - Distribution of hydrolytic activity catalyzes the biotransformation of
      prednisolone 21-acetate in human skin.
AB  - We investigated the distribution of hydrolytic enzymes which metabolize
      prednisolone 21-acetate (PNA) to prednisolone (PN) in human skin. Km (Michaelis
      Menten constant) and Vmax (maximum rate) of hydrolytic enzyme in human skin was
      25.1 microM and 0.46 nmol/min/mg protein, respectively. Specific activities of
      hydrolysis in dermis and epidermis were similar and, in consideration to their
      thickness, hydrolytic activity in epidermis was 12.1 times higher than in dermis.
      Moreover, the highest amount of metabolite (PN) was found at 80-120 microm from
      the skin surface by skin slicing. Therefore, hydrolytic activity which
      metabolized PNA was distributed in epidermis, especially in the basement membrane
      area; epidermis borders dermis in this area and the papillary plexus is reached
      just beneath the dermal papillae. These results suggest that the distribution of
      hydrolytic activity in human skin may prevent certain substances from entering
      the systemic circulation in their unhydrolyzed form.

PMID- 11464102
TI  - Metabolism of prednisolone 21-acetate in hairless mouse skin.
AB  - We investigated the hydrolytic activity of prednisolone 21-acetate (PNA) to
      prednisolone (PN) in an enzyme solution composed of esterase and skin homogenates
      from hairless mice. The values of the Michaelis-Menten constant obtained from
      hairless mouse skin and esterase solution were 14.2 and 10.2 microM,
      respectively; conversely, the value of the maximum rate from hairless mouse and
      esterase solution were 0.67 and 1,886 nmol/min/mg protein, respectively. To
      examine the effect of enzymatic inhibitors on hydrolytic activity, five enzymatic
      inhibitors, 3,4-dichloroisocoumarine (DCIC), N-tosyl-L-phenylalanine chloromethyl
      ketone, iodoacetamide, p-hydroxymercuribenzoic acid (HMBA) and sodium
      dodecylsulfate, were added to the enzyme solution. Sixty-eight percent of
      hydrolytic activity in skin homogenates were not deactivated by DCIC which
      completely inhibited the enzymatic activity in esterase solution. We also studied
      the localization of hydrolytic enzyme with a subcellular faction: 66 and 11% of
      specific activity existed in microsome (Ms) and cytosol (Cp) fractions,
      indicating that the hydrolytic activity of PNA was included mainly in the Ms
      fraction. Hydrolytic activity in Ms and Cp fractions was different from
      sensitivity to enzymatic inhibitor; DCIC inhibited activity in the Ms fraction
      and, on the other hand, HMBA inhibited it in the Cp fraction. Therefore, Ms and
      Cp fractions in skin homogenates include a different esterase isoform and the
      metabolism of PNA to PN in hairless mouse skin is mediated by these isoforms.

PMID- 11464103
TI  - Penetration kinetics of 8-methoxypsoralen after 8-methoxypsoralen bath procedure
      with and without UVA irradiation.
AB  - Administration of 8-methoxypsoralen (8-MOP) in a dilute bath water solution is an
      effective therapeutic alternative for systemic application of 8-MOP, avoiding
      systemic side effects such as nausea and cataractogenesis. The aim of our study
      was to determine the epicutaneous penetration of 8-MOP in a dilute bath water
      solution with and without additional UVA irradiation in human skin under in vitro
      conditions. To simulate the PUVA bath procedure, 8 skin samples were exposed to
      radioactively labeled 8-MOP in a water solution. After 20 min, the test solution
      was removed and the skin surface was dried. Immediately after the bath procedure,
      4 of the skin samples were irradiated with 0.5 J/cm2 UVA. During a test period of
      15 h, the 8-MOP penetration was observed. In both test groups (with and without
      UVA irradiation) 8-MOP permeated through all skin layers between 30 min and 1 h
      after application. Compared to the unirradiated skin samples, the UVA-irradiated
      skin samples showed a significantly slower increase and a lower maximum of 8-MOP
      permeation. Following our results, UVA irradiation of 8-MOP-exposed skin samples
      led to a significantly decreased permeation rate. This might be due to UVA
      induced links between 8-MOP molecules and human DNA. In addition, we investigated
      the levels of radioactivity emitted by tritium-labeled 8-MOP in stratum corneum,
      epidermis and dermis up to 30 min after 8-MOP bath in two further test groups
      with and without additional UVA irradiation. The statistical analysis revealed no
      significant differences between these two test groups. Thus, the levels of
      radioactivity remained constant in the epidermis and dermis during the test
      period of 30 min. Since the levels of radioactivity were constant up to 30 min
      after UVA irradiation, a previously supposed marked loss of 8-MOP concentration
      might not be responsible for the rapid extinction of observed in vivo
      photosensitivity within 1 h after PUVA bath observed in vivo in human skin.

PMID- 11464104
TI  - Dithranol and dimethylfumarate suppress the interferon-gamma-induced up
      regulation of cytokeratin 17 as a putative psoriasis autoantigen in vitro.
AB  - In psoriasis an etiopathogenetic vicious circle has been hypothesized in which
      disease manifestation is triggered by skin-specific autoantigen structures.
      Autoreactive T cells are supposed to mediate inflammation and hyperproliferation
      in the epidermopapillary compartment, positively feeding back the expression and
      accessibility of decisive antigen structures. Recently an epitope within
      cytokeratin 17 (K17) has been described as such a putative psoriasis autoantigen,
      which is moreover known to be up-regulated under the influence of proinflammatory
      interferon-gamma (IFN-gamma), which is abundantly detected in psoriatic plaques.
      The present study proposes an in vitro model for this presumptive IFN-gamma/K17
      autoimmune loop, i.e. the incubation of hyperproliferative human HaCaT
      keratinocytes with 25 U IFN-gamma/ml for 72 h. This treatment led to a
      significant up-regulation of K17 protein expression (> or =300%) measured by flow
      immunocytometry as compared to the untreated control (100%, p < or = 0.05).
      Preincubation with a subcytotoxic and antiproliferative dithranol concentration
      as low as 0.3 microM for 2 h prior to the IFN-gamma exposure resulted in a K17
      expression that was significantly lower than the IFN-gamma-induced K17 expression
      reference level. The IFN-gamma-induced K17 expression was also significantly
      lowered by coincubation with a subcytotoxic and nonantiproliferative
      concentration of 3 microM dimethylfumarate. The data indicate for dithranol and
      dimethylfumarate that a part of their antipsoriatic mode of action may be related
      to a direct down-regulation of putative psoriasis autoantigen structures.

PMID- 11464105
TI  - Tacalcitol, an active vitamin D3, induces nerve growth factor production in human
      epidermal keratinocytes.
AB  - The human epidermal keratinocyte cell line K-TL-1, developed from a benign
      epidermal tumor, was cultured in the presence of the synthetic vitamin D3
      analogue tacalcitol [1alpha,24(R)-dihydroxyvitamin D3] to assess the effects on
      the production of nerve growth factor (NGF). Confluent K-TL-1 cells were cultured
      with 10(-8) M of tacalcitol. Supernatants and cell homogenates were collected and
      NGF concentrations were determined by enzyme-linked immunosorbent assay. The
      concentration of NGF in the supernatants of cultures treated with tacalcitol
      peaked within 24 h after the start of tacalcitol treatment and remained stable
      for 96 h. This NGF induction caused by tacalcitol was dose-dependent, showing an
      ED50 between 10(-10) and 10(-9) M. Induction of NGF mRNA expression by tacalcitol
      was also observed by RT-PCR, indicating that tacalcitol induced NGF expression
      through transcriptional activation. These results suggest that active vitamin D3
      could treat peripheral neuropathy by inducing NGF production in the skin.

PMID- 11464106
TI  - Immunomodulation induced by Avene spring water on Th1- and Th2-dependent cytokine
      production in healthy subjects and atopic dermatitis patients.
AB  - Avene spring water (ASW) is commonly used in France for treating atopic
      dermatitis and psoriasis. Previous works demonstrated modulation of cell membrane
      fluidity by ASW. The aims of the present study were (a) to investigate a possible
      in vitro effect of ASW on Th1- and Th2-dependent cytokine production using
      peripheral blood mononuclear cells from healthy individuals and (b) to
      investigate both the in vitro effect of ASW on AD patients' cells and the in vivo
      cellular and clinical modifications induced by a 3-week Avene Medical Spa water
      cure (AMSWC). The effect of ASW was tested on lymphocyte cultures, which were
      stimulated in vitro by various mitogens and a superantigen of staphylococcal
      origin. The lymphocyte proliferation and the production of the cytokines IL-2, IL
      4 and IFN-gamma were tested. The results showed that ASW-containing medium
      enhanced the lymphoproliferative response to some mitogens. IL-2 and IFN-gamma
      production were also increased in stimulated culture supernatants. Conversely,
      ASW-containing medium induced a decrease in IL-4 production by normal peripheral
      blood lymphocytes. Furthermore, AMSWC was able to amend the clinical features as
      well as the immunological Th2 profile of atopic dermatitis.

PMID- 11464107
TI  - Nutrition and prostate cancer.
AB  - Nutrition is apparently a major risk factor for the development and progression
      of prostate cancer. Based on experimental studies and epidemiologic data mainly
      from case-control studies or cohort studies, there is strong evidence that
      reduction of the total energy consumption, a diet comprising less than 30% fat,
      and increased intake of phytoestrogens, vitamins D and E and selenium could yield
      a decreased prostate cancer incidence. Furthermore, some of these measures appear
      to have antitumoral capacity even in the presence of the disease. These
      observations have provided a rationale to forward large prospective trials on
      dietary interventions to prove the efficacy of the concept and further delineate
      the correlation between nutritional compounds and prostate cancer risk. These
      chemoprevention trials are either aiming a reduction prostate cancer incidence or
      a decrease in tumor progression. Depending on the study design, large numbers of
      individuals need to be enrolled and long follow-up intervals are required thus
      making such trials highly complex and cost-intensive. However, regarding the
      potential relevance of chemoprevention on public health, further efforts to
      identify nutritional factors affecting prostate cancer growth are warranted.

PMID- 11464108
TI  - Why surgery for incontinence and prolapse fails.

PMID- 11464109
TI  - Comparison of Gleason scores from sextant prostate biopsies and radical
      prostatectomy specimens.
AB  - OBJECTIVES: We compared the Gleason scores obtained from sextant prostate biopsy
      and radical prostatectomy (RP) specimens in patients with localized prostate
      cancer. PATIENTS AND METHODS: Sixty-one patients having a clinical diagnosis of
      localized prostate cancer underwent needle biopsy under transrectal
      ultrasonography (TRUS) and RP. Grading and staging were assigned based on Gleason
      scores and the TNM system, respectively. RESULTS: Mean patient age was 65.5 +/-
      13.43 years and mean PSA level was 14.69 +/- 3.95. Mean Gleason score for
      prostate biopsy and RP specimen were 5.85 +/- 0.7 and 6.34 +/- 1.44,
      respectively. With respect to clinical stage, there were 20 patients in stage 1
      and 41 patients in stage 2 prostate cancer. Comparing the Gleason scores, the
      biopsy score was lower in 26 (42.26%) and higher than RP specimens in 7 (11.84%)
      cases, and there was agreement between the biopsy and RP specimens in 28 (45.9%)
      patients. The difference between the two Gleason scores was +/- 1 for 18 patients
      (29.5%) and +/- 2 or more for 17 patients (27.86%). CONCLUSION: In our study,
      high Gleason score biopsies with elevated PSA level (>10 ng/ml) were risk factors
      for extraprostatic extension, and we demonstrated that Gleason scores were
      significantly correlated with seminal vesicle and lymph node invasion (p < 0.05).
      The Gleason scores of biopsy and RP specimens agreed with 45.9% of TRUS-guided
      sextant prostate biopsies, and this ratio was 91.1% in moderately differentiated
      tumors

PMID- 11464110
TI  - Repair of inguinal hernias using the mesh technique during extraperitoneal pelvic
      lymph node dissection.
AB  - PURPOSE: This article describes our experience of using a totally extraperitoneal
      approach for endoscopic pelvic lymphadenectomy and inguinal hernia repair with
      the mesh technique in one procedure. MATERIALS AND METHODS: A total of 52
      patients underwent modified pelvic lymph node dissection for the staging of
      prostate cancer. Eight of them had hernia defects; 1 was recurrent. Five patients
      with direct and 3 patients with indirect inguinal hernias were treated by totally
      extraperitoneal hernia repair with the placement of a mesh measuring at least 10
      x 15 cm (prolene mesh with incision and flap). RESULTS: The mean duration of the
      lymphadenectomy itself was decreased from 150 min (first 20 patients) to 70 min
      (n = 21-52). The mean additional procedure time for hernioplasty was 15 min. The
      overall lymph node-positive rate was 9.6%. The complication rate was 7.7%. Four
      patients developed symptomatic lymphoceles, 1 of whom developed deep venous
      thrombosis. No complications occurred which were attributed to hernia repair.
      Morbidity did not rise, and hospitalization time did not increase for the
      patients who underwent hernioplasty. There were no recurrences or neuralgias on
      follow-up up to 2 years. CONCLUSIONS: By avoiding entry into the peritoneal
      cavity, the extraperitoneal approach obviates intra-abdominal complications
      (ileus, bowel injury, peritonitis) in both techniques. The extraperitoneal
      approach for pelvic lymph node dissection allows concomitant inguinal hernia to
      be repaired with low morbidity and within an acceptable operating time.

PMID- 11464111
TI  - Renal cell carcinoma in renal graft recipients and donors: incidence and
      consequence.
AB  - INTRODUCTION AND OBJECTIVES: Numerous studies have reported an increasing
      incidence of small renal cell carcinoma (RCC). De novo RCC in a renal allograft
      is a rare event and has special implications in renal transplant recipients. The
      objective of this study was to retrospectively evaluate the incidence of RCC in
      renal graft recipients and donors and to determine a procedure in cases with
      newly detected small renal tumors at the time of kidney preparation before
      transplantation. MATERIAL AND METHODS: We mailed a questionnaire to 38 German
      transplant clinics and received answers from 27 centers. A total of 10,997 renal
      graft recipients were included in the period of 1990-1998. RESULTS: In 30 kidneys
      (0.273%) RCC was detected at the time of preparation before transplantation.
      There were 23 male and 3 female donors. No bilateral RCC was described. The mean
      age of the donors with RCC was 50.9 years (range 37-72 years). The tumors had a
      mean size of 2.2 cm (range 0.4-6 cm). 67% of the patients had a renal tumor
      smaller than 20 mm. In 26/27 centers the decision to transplant relies on the
      result of the immediate section for microscopic examination. 16 patients (0.145%)
      developed RCC 3-12 years after renal transplantation (mean 7.4 years). The mean
      tumor size was 2.5 cm (range 2-2.8 cm). In 50% a grade 1 and in the other 50% a
      grade 2 carcinoma was found. CONCLUSIONS: Because of the RCC incidence in donor
      candidates we recommend an ultrasound screening of the native kidneys before
      renal explantation and an immediate preparation of the kidney surface especially
      in donors older than 45 years. In cases with small renal lesions we recommend an
      immediate section for microscopic examination before transplantation to prevent
      tumor implantation into an otherwise healthy patient. The frequency of RCCs after
      renal transplantation necessitates careful clinical and instrumental examinations
      in organ-transplanted recipients both before and at regular intervals after
      transplantation, including the patient's kidneys.

PMID- 11464112
TI  - Management of renal angiomyolipoma in complex clinical situations.
AB  - Renal angiomyolipoma (AML) is associated with complex clinical situations such as
      tumour in a solitary kidney, bilateral, large or multicentric tumours or those
      associated with tuberous sclerosis (TS) or pregnancy. Management in these
      situations may be challenging. Fifteen patients (20 kidneys) were admitted with
      symptomatic AML over last 10 years. Eleven patients had one or the other
      complicating factor. Ten patients had a tumour of >10 cm, 4 had TS, 5 had
      multiple and bilateral tumours, 1 patient was pregnant and 1 had a solitary
      functioning kidney. With the newer imaging modalities correct diagnosis was
      possible in 12 cases and renal cell carcinoma (RCC) was suspected in 3 cases.
      Selective angioembolization (SAE) was done in 3 patients, which successfully
      controlled bleeding in all. Nephron-sparing surgery (NSS) was performed in 5
      patients. Total nephrectomy was done in 4 cases, in 3 due to suspicion of RCC and
      in 1 due to extensive involvement of the kidney. Three patients with multiple and
      bilateral tumours were chosen for conservative treatment and none developed
      recurrence of bleeding on strict follow-up. In a pregnant patient, bleeding was
      successfully controlled with angioembolization. However, 1 patient with a
      solitary functioning kidney with large-sized tumour (20 x 18 cm) underwent NSS.
      In conclusion, the basis of management of AML is preservation of renal tissue,
      which can be effectively achieved with SAE or NSS. In a solitary functioning
      kidney, NSS or SAE is the ideal treatment, if feasible. The patients in the TS
      group are usually more complicated and require life-long follow-up after initial
      management with NSS or SAE. Pregnant AML patients can be safely managed with SAE.
      Conservative treatment without any intervention and regular follow-up may be more
      helpful in some patients with multiple, bilateral extensive tumours.

PMID- 11464113
TI  - p53 and bcl-2 overexpression as associated risk factors in patients 40 years old
      or less with transitional cell carcinoma of the bladder.
AB  - OBJECTIVES: Transitional cell carcinoma (TCC) of the bladder in younger patients
      has historically a favourable prognosis. bcl-2 and p53 genes are implicated in
      cell cycle regulation with roles on programmed cell death. Presence of nuclear
      accumulation of p53 and cytoplasmic accumulation of bcl-2 were proposed to confer
      a growth advantage to tumour cells. In this study, we investigated the roles of
      p53 and bcl-2 as prognostic factors in TCC of bladder in patients younger than 40
      years. PATIENTS AND METHODS: From 1986 to 1998, 25 patients younger than 40 years
      were treated for TCC of bladder in our hospital. Of the tumour specimens, 24 were
      adequate for evaluating p53 and bcl-2 oncoproteins (group I). As a control (group
      II), we randomly selected 30 patients older than 50 years treated for bladder
      cancer in this period. Two oncoproteins were detected by immunohistochemical
      analysis in paired tumour tissue specimens in both groups. Retrospectively
      obtained clinical follow-up data were available, with a mean follow-up of 44 and
      25.5 months in groups I and II, respectively. Relations between tumour
      recurrences and progression with positivity of bcl-2 and p53 were investigated.
      RESULTS: Expression of bcl-2 was observed in 13 (54.1%) and 11 (36.7%) and
      nuclear p53 accumulation in 9 (37.5%) and 17 (56.7%) of groups I and II,
      respectively. In the presence of p53 expression, tumours showed significantly
      more progression in group I (55 vs. 6.7%) and group II (41.1 vs. 0%). Recurrence
      rates were not significantly different in tumours with and without nuclear p53
      overexpression in both groups. Also, recurrence and progression rates were not
      significantly different in tumours with and without cytoplasmic bcl-2
      overexpression in both groups. Grade (G) and stage appeared as important
      prognostic factors in both groups since 60% of GIII tumours showed progression in
      group I, but none of GI and GII tumours. Similarly, 75% of T3 tumours progressed,
      while these rates were 25 and 25% for T1-T2 tumours in group I. In group II,
      31.2, 25 and 0% of GIII, GII and GI tumours progressed, while 50, 41.6 and 0% of
      T3, T2 and T1 tumours progressed, respectively. CONCLUSIONS: Nuclear p53
      expression in TCC appears to be associated with a poorer prognosis in both
      younger and older patients. Although cytoplasmic bcl-2 overexpression is found in
      the majority of tumours in the younger group, it is not associated with tumour
      progression and recurrence.

PMID- 11464114
TI  - Long-term behavior of secretory immunity in ileocecal and ileal orthotopic
      neobladders.
AB  - OBJECTIVE: To compare secretory immunity in cecal and ileal orthotopic
      neobladders, and to detect its permanence over time. PATIENTS AND METHODS: IgA
      was studied in the urine of 33 patients with ileocecourethrostomy (ICUS) and 13
      patients with ileal reservoir (IR). The mean follow-up was 55 months. Results
      were compared in terms of the type of operation, a healthy control group, and the
      time since surgery. RESULTS: Urinary IgA levels were significantly higher in ICUS
      and IR patients than in normal controls. No significant differences in IgA
      concentrations were detected in patients with different reservoirs and with
      regard to time. CONCLUSION: Both the reservoirs maintain the function of
      producing IgA. In particular no differences were detected over time and urine
      could be a permanent antigenic stimulus. IgA could be considered an adjunctive
      factor for upper urinary tract protection. For this reason we prefer to use a
      simple, indirect antireflux mechanism, thus avoiding direct manipulation of the
      uretero-intestinal anastomosis.

PMID- 11464115
TI  - Diagnosis of abdominal bilateral cryptorchidism: HCG stimulation test.
AB  - A diagnostic stimulation test with hCG (Pregnyl) was performed in clinically
      healthy boys and was used to diagnose cases of bilateral abdominal
      cryptorchidism. In clinical andrology, this test may be applied as a noninvasive
      and highly sensitive method.

PMID- 11464116
TI  - Urinary composition and lithogenic risk in normal subjects following oligomineral
      versus bicarbonate-alkaline high calcium mineral water intake.
AB  - OBJECTIVE: A normal dietary calcium intake to reduce intestinal oxalate
      absorption is essential to avoid recurrence of calcium oxalate stone formation.
      It is also important in the prevention of osteopenia in idiopathic
      hypercalciuria. The calcium content of waters used for hydration may vary from
      very low to relatively high and is an important factor in prevention or
      additional risk of stone formation. Therefore, the effect of drinking mineral
      waters of different calcium concentrations on lithogenic risk factors was studied
      in normal volunteers. MATERIALS AND METHODS: Normal subjects were divided into
      two groups of 11 and 10 individuals each. All followed a prescribed diet with an
      average calcium content of 800 mg/day. The water intake for hydration consisted
      of 2 liters of an oligomineral water with a low calcium content, <20 mg/l (group
      A) or of a bicarbonate alkaline water with a high calcium content, 370 mg/l
      (group B). RESULTS: Diuresis increased similarly in both groups; urine calcium
      increased by about 80 mg/day in group B. A rise in urine oxalate was observed in
      both groups, along with the increased urine volume. Osmolar excretion increased
      in group B; urine osmolality decreased significantly only in group A. In spite of
      the increase in calciuria in group B, Ca/citrate ratio was constant, due to an
      increase in citrate excretion. Inter-group differences in terms of activity
      products of calcium phosphate, calculated according with Tiselius's methods, were
      found. The differences in AP(CaP) index 1 and AP(CaP) index 2 were significant,
      with higher values in group B, who drank the bicarbonate alkaline mineral water.
      CONCLUSIONS: Increased water intake between meals to prevent renal stone
      recurrence should preferably be achieved with a relatively low calcium water and
      calcium-rich mineral waters should be avoided.

PMID- 11464117
TI  - Combination of transcutaneous electrical nerve stimulation and ondansetron in
      preventing cisplatin-induced emesis.
AB  - OBJECTIVE: To find out whether the combination of transcutaneous electrical nerve
      stimulation (TENS) and ondansetron had an increased antiemetic effect. MATERIALS
      AND METHODS: Fourteen testis and 11 bladder cancer patients were scheduled for 4
      cycles of bleomycin-etoposide-cisplatin (BEP) or methotrexate-vinblastine
      etoposide-cisplatin (MVEC) combination chemotherapy, respectively. At each cycle
      the whole cisplatin dose was given in 1 day that is 100 mg/m(2)/day in the BEP
      and 70 mg/m(2)/day in the MVEC protocols. Ondansetron was given at a dose of 12
      mg/day and TENS was applied by commercially available 'Relief Band'(Maven Labs,
      Inc., Citrus Heights, Calif., USA). The first 3 cycles of each case were blindly
      randomized to one of the following regimens; TENS vs. ondansetron vs. a
      combination of both. The regimens were applied during the administration of
      cisplatin and the patients were asked to report their nausea according to a scale
      between 0 to 10. Also for each regimen the number of emetic attacks experienced
      during the administration of cisplatin was recorded by the same observer. Then
      the scores of each regimen were compared. RESULTS: The mean nausea scores for
      regimens TENS, ondansetron and TENS + ondansetron were found to be 5.12 +/- 2.54,
      3.0 +/- 1.71 and 0.8 +/- 0.96, respectively. Ondansetron was better than TENS in
      preventing nausea (p = 0.000). However the combination of TENS and ondansetron
      resulted in a significant decrease in nausea scores when compared to TENS alone
      (p = 0.000) or ondansetron alone (p = 0.000). The mean number of emetic attacks
      for the TENS, ondansetron and TENS + ondansetron regimens were 3.16 +/- 1.84,
      1.64 +/- 1.44 and 0.56 +/- 0.82, respectively. A statistically significant
      difference was present between the number of emetic attacks observed with the
      TENS + ondansetron combination and TENS alone (p = 0.000) or ondansetron alone (p
      = 0.001). Ondansetron was again better than TENS in preventing emetic attacks (p
      = 0.001). CONCLUSION: The use of TENS as an adjunct to ondansetron therapy has
      provided significant benefit in preventing nausea and emetic attacks caused by
      cisplatin.

PMID- 11464118
TI  - Are adverse effects of sildenafil also caused by inhibition of diamine oxidase?
AB  - BACKGROUND: Sildenafil citrate (Viagra), a drug used to treat erectile
      dysfunctions, causes adverse reactions such as headache, flushing or nasal
      congestion. Sildanefil's potency as inhibitor of diamine oxidase was
      investigated, as side effects may also be induced by histamine itself due to an
      impaired histamine metabolism. METHODS: Placental diamine oxidase inhibition
      experiments were performed with consecutive dilutions of sildenafil citrate (10(
      5) to 10(-9) mol/l). In 9 male volunteers in vivo diamine oxidase inhibition was
      investigated after taking 100 mg sildenafil (Viagra). RESULTS: Sildenafil citrate
      did not inhibit placental diamine oxidase either in vitro or in vivo. However,
      infusion of 300 mg of cimetidine inhibited diamine oxidase activity by 27 +/- 7%
      15 min after infusion, demonstrating that drugs may inhibit diamine oxidase in
      vivo. CONCLUSION: As side effects of sildenafil are not caused due to inhibition
      of diamine oxidase, sildenafil citrate seems to be harmless for patients
      suffering from histamine intolerance.

PMID- 11464119
TI  - Supramaximal stimuli do not evoke a maximal contraction in urinary bladder smooth
      muscle fibers.
AB  - BACKGROUND: Smooth muscle fibers can be stimulated with an electrical field, high
      potassium or carbachol. We studied the effect of combined, supramaximal
      stimulation on the isometric force and the maximum shortening velocity of the pig
      urinary bladder. MATERIALS AND METHODS: After determining the dose response curve
      of each stimulation type, we stimulated 8 fibers with cumulative addition of
      supramaximal stimuli. RESULTS: The isometric force elicited with either
      potassium, carbachol or electrical field stimulation alone was the same for each
      stimulus. After addition of a second or third different supramaximal stimulus,
      the force further increased to a value that was on average 40% higher.
      CONCLUSIONS: Carbachol, high potassium or electrical field stimulation work
      through different stimulation pathways. Maximum stimulation with one of the
      stimuli does not result in a maximum isometric force development and maximum
      shortening velocity.

PMID- 11464120
TI  - Finasteride: a long-term follow-up in the treatment of recurrent hematuria
      associated with benign prostatic hyperplasia.
AB  - OBJECTIVES: To assess the effectiveness and long-term results after finasteride
      treatment of recurrent hematuria associated with benign prostatic hyperplasia
      (BPH). MATERIALS AND METHODS: The study comprised 80 patients, aged 62-86 (mean
      74) years, of whom 50 received finasteride 5 mg once daily for 4 years and 30
      were used as controls. Patients with malignancy, severe hepatic or renal failure
      and hematologic disorders were excluded. Patients were divided into 3 groups
      according to the severity of hematuria (minor, moderate, severe). All patients
      were followed up at 3, 12, 24 and 48 months. RESULTS: The follow-up ranged from 8
      to 48 (mean 22) months in the finasteride group and 3-42 (mean 23) months in the
      control group. Hematuria recurrence rates were 6/50 (12%) and 23/30 (77%) in the
      finasteride and control groups, respectively. Surgical treatment was needed in 6
      patients of the finasteride group and 19 of the control group. Patients with
      minor hematuria experienced no recurrence of symptoms in the finasteride group in
      contrast to 13 of 17 patients in the control group. For the patients with
      moderate hematuria, recurrence of symptoms was observed in 3 of 13 in the
      finasteride group and 3 of 5 in the control group. Three of six patients with
      severe hematuria had a recurrence of symptoms after finasteride treatment in
      contrast to 7 of 8 in the control group. CONCLUSION: Finasteride has proved to be
      a safe, well tolerable and effective medication in reducing or preventing
      recurrent hematuria related to BPH.

PMID- 11464121
TI  - Calcium oxalate crystal attachment to cultured rat kidney epithelial cell, NRK
      52E.
AB  - Madin-Darby canine kidney (MDCK) cells have been used in research on crystal
      adhesion to epithelial cells. Recently, matrix proteins were identified, and
      studies of the genes and proteins expressed in renal epithelial cells have become
      active. The present study confirms the usefulness of the NRK-52E cell line,
      derived from the rat, in the study of attachment with calcium oxalate crystals.
      The calcium oxalate crystal suspension was distributed on top of the cells. After
      incubation, the monolayers were rinsed to remove non-associated crystals. After
      fixation, the association of crystals and NRK-52E cells was visualized using
      scanning electron microscopy. Calcium oxalate crystals were attached to the
      surface of NRK-52E cells. Under high magnification, many of the microvilli of the
      cells had elongated towards the crystals, and microvilli projections appeared to
      catch the crystals. The NRK-52E cell line is useful in the study of attachment
      between crystals and urinary epithelial cells in the kidney, especially for the
      regulation and analysis of genes and proteins.

PMID- 11464122
TI  - Tomorrow's world today--evidence-based medicine.

PMID- 11464123
TI  - Hematuria due to immune-mediated thrombocytopenic purpura.

PMID- 11464124
TI  - Haematuria presenting six years after a pelvic fracture.
AB  - Pelvic fractures are frequently associated with injuries to the lower
      genitourinary tract. However, most described injuries are noted at the time the
      fracture is sustained. We describe the case of a 63-year-old man who presented
      with haematuria 6 years after sustaining an 'open-book'-type pelvic fracture.

PMID- 11464125
TI  - Synchronous bladder augmentation and living related kidney transplantation.
AB  - Ileocystoplasty for enlargement of bladder capacity in conjunction with renal
      transplantation has been described in several cases. However, the surgical
      approach has been accomplished as a two-stage procedure. We report the case of a
      21-year-old female myelomeningocele patient with end-stage renal insufficiency
      who was treated with ileocytstoplasty and living related renal transplantation at
      a single stage. Convalescence remained uneventful. On follow-up 13 months after
      the operation, the renal parameters remained stable.

PMID- 11464126
TI  - Collecting duct carcinoma.
AB  - Collecting duct carcinoma of the kidney is a rare variant of renal cell
      carcinoma. Hematuria is the most common presenting symptom. This tubulopapillary
      tumor arises from or differentiates forward to medullary collecting tubules. It
      is typically centered on the medulla of the kidney and extends into the cortex
      with a desmoplastic reaction. There are few reports documenting the clinical
      presentation and long-term prognosis. We describe a case of this uncommon tumor
      with clinical, histological and immunohistochemical features and review the
      literature.

PMID- 11464127
TI  - Indolent behaviour of low-grade B cell lymphoma of mucosa-associated lymphoid
      tissue arising in the kidney.
AB  - We report a case of low-grade MALT lymphoma (mucosa-associated lymphoid tissue)
      arising in the kidney. It had very indolent behaviour with multiple extranodal
      relapses (parotid gland, orbit, skin, breast, prostate) over a period of 13
      years; presently, the patient is asymptomatic.

PMID- 11464128
TI  - Adult testicular pure yolk sac tumor.
AB  - Here we describe the clinical, ultrasonographic and histological features of a
      rare pure adult yolk sac tumor detected in the right testis of a 44-year-old
      male. Due to the rarity of this neoplasm (less than 10 cases have been reported),
      there is no unanimous consensus for therapy following inguinal orchiectomy. We
      believe that nerve-sparing retroperitoneal lymph node dissection could be
      potentially curative and useful for future interpretations of this tumor's
      potential evolution.

PMID- 11464129
TI  - Primary lymphoma of the epididymis: case report and review of the literature.
AB  - OBJECTIVE: To report an extremely rare clinical pathological observation of a
      case of primary lymphoma of the epididymis, without testicular or systemic
      involvement, and to update the relevant literature. MATERIALS AND METHODS: A 25
      year-old white male patient complaining of right scrotal pain was referred to our
      department. Clinical examination detected a hard painful mass at the right
      epididymal head. Epididymitis was diagnosed and conservative therapy with
      antibiotics and anti-inflammatory drugs was given. After 2 months of therapy the
      patient was admitted to our department because a tumor was suspected. Tumor
      markers were normal. Right scrotal exploration was performed through a standard
      inguinal incision. The epididymal head was completely replaced by a hard white
      mass. Fresh frozen sections indicated a malignant tumor. Right radical
      orchiectomy was performed. RESULTS: High-grade primary epididymal non-Hodgkin's
      lymphoma with diffuse large cells (group G according to the Working Formulation)
      was diagnosed. Clinical pathological staging detected stage IE (extranodal)
      primary epididymal lymphoma. The patient was referred to the Hematologic Unit for
      combined chemotherapy, according to the VACOP-B protocol. After an 18-month
      follow-up the patient is well and disease free. CONCLUSIONS: When an epididymal
      mass does not benefit from medical treatment, scrotal exploration and fresh
      frozen sections of the lesion should be done. The possible bilateral involvement
      by primary epididymal lymphoma has to be kept in mind. Radical orchiectomy is the
      treatment of choice for primary lymphoma of the epididymis. Adjuvant chemotherapy
      is indicated in high-grade malignant lymphoma. Prognostic parameters of the
      disease may be the grade of malignancy and the size of the tumor.

PMID- 11464130
TI  - Testicular sarcoid.
AB  - Sarcoidosis occurs rarely in Caucasian males and seldom involves the testis. We
      report an unusual case of asymptomatic testicular sarcoid in a Caucasian man.

PMID- 11464131
TI  - Liposarcoma of the spermatic cord.
AB  - A 64-year-old male presented with a 4-year history of a mass in the left scrotum.
      Radical orchiectomy was performed. Pathological analysis demonstrated a well
      differentiated liposarcoma. No evidence of recurrence or metastasis has been
      noted during the 3-month follow-up without any postoperative adjuvant therapy.

PMID- 11464132
TI  - Clear cell adenocarcinoma of the male urethra in association with so-called
      nephrogenic metaplasia.
AB  - A clear cell adenocarcinoma of the urethra associated with so-called nephrogenic
      metaplasia occurring in a 57-year-old male patient is presented. Ten months
      following total urethrectomy, multiple pulmonary metastases had developed. The
      patient died 2.5 years after surgery. The possible histogenesis of clear cell
      adenocarcinoma of the lower urinary tract - reported to develop in the male
      urethra only in a very few cases - is reviewed briefly. We favor an origin from
      preexisting nephrogenic metaplasia as one of the possible histogenetic pathways.

PMID- 11464133
TI  - Priapism associated with intracavernosal injection of cocaine.
AB  - We describe a case of priapism associated with intracavernosal injection of
      cocaine and our treatment approach and discuss the pathophysiologic mechanisms of
      cocaine-induced priapism and offer a physiologic approach to its management.

PMID- 11464134
TI  - Cavernositis following intracavernous injection of vasoactive drugs.
AB  - Intracavernous injection is one of the most common treatments of erectile
      dysfunction. Infectious complications are rare, but hazardous. We report the case
      of a 44-year-old to stress the importance of patient supervision and drug
      prescription.

PMID- 11464135
TI  - Surgical management of isolated bilateral adrenal metastases from colon carcinoma
      causing adrenal insufficiency.
AB  - Adrenal insufficiency due to histologically proven bilateral metastatic adrenal
      involvement from colon cancer has been clinically reported only twice. Surgical
      treatment of bilateral adrenal metastases is seldom performed, since other
      metastatic localizations are usually concomitant. To the best of our knowledge,
      we report the first case of relatively long-term disease-free survival after
      bilateral adrenalectomy in a patient with adrenal insufficiency due to bilateral
      metastases from colon carcinoma.

PMID- 11464136
TI  - Vaginal and omental metastasis from superficial bladder cancer.
AB  - A 58-year-old lady, diagnosed as having superficial bladder cancer 6 years
      earlier presented to us with a vaginal nodule. Investigations and biopsy revealed
      a metastatic transitional cell carcinoma in the pelvic lymph nodes, omentum and
      vagina.

PMID- 11464137
TI  - Sublingual meloxicam for renal colic.

PMID- 11464139
TI  - Apoptotic effects in primary human umbilical vein endothelial cell cultures
      caused by exposure to virion-associated and cell membrane-associated HIV-1 gp120.
AB  - During the course of HIV-1 infection, free virus, infected cells, and free HIV-1
      proteins circulate within the host, exposing the host endothelium to these viral
      factors. We have previously presented evidence showing that soluble HIV-1 gp120
      protein interacts with chemokine receptors on primary human endothelium and
      (through those interactions) induces apoptosis as well as other intracellular
      effects. The current study examines the effect of exposure of vascular
      endothelium to gp120 IIIb expressed on the surface of Jurkat cells and in the
      context of viral particles. Apoptosis was observed in human umbilical vein
      endothelial cell (HUVEC) cultures exposed to gp160-transfected Jurkat cells as
      well as to virion particles with gp120 on their surface. Additional experiments
      show that this apoptotic effect was caused by gp120 protein acting through
      chemokine receptors on the HUVEC surface, primarily the CXCR4 receptor. At higher
      concentrations of gp120, this lymphotrophic variant, which has been shown to
      interact predominantly with CXCR4, seems to interact with and induce apoptosis
      through the CCR5 receptor. Finally, this apoptotic effect in HUVEC cultures
      occurs at low levels of the inducing agent, gp120, on cell membranes or on virion
      particles. These results demonstrate that HIV-1 gp120 is capable of interacting
      with and killing vascular endothelial cells in multiple in vivo contexts.

PMID- 11464140
TI  - Pathogenic determinants of the mucosally transmissible CXCR4-specific
      SHIV(SF33A2) map to env region.
AB  - Infection of rhesus macaques with chimeric simian-human immunodeficiency viruses
      (SHIV) is an established method to study AIDS pathogenesis and is increasingly
      used to assess the efficacy of vaccine and antiviral candidates. For these
      reasons, a detailed understanding of those molecular determinants, which confer
      pathogenic potential to SHIV viruses, should assist in both rational experimental
      design and interpretation of results. In this report, we describe the development
      and in vivo characterization of a pathogenic molecular clone, SHIVSF33A2, which
      contains an envelope sequence derived from the CXCR4-dependent isolate, HIV
      1SF33. Proviral DNA, amplified from a rhesus macaque infected with the pathogenic
      isolate SHIVSF33A, was substituted into the corresponding region of the parental,
      nonpathogenic SHIVSF33 genome creating the molecular clone SHIVSF33A2. Coreceptor
      specificity of SHIVSF33A2 was determined to be CXCR4 specific. Naive rhesus
      macaques were productively infected after a single exposure to cell-free
      SHIVSF33A2 by either the intravenous (IV) or intravaginal (IVAG) routes. Animals
      infected with SHIVSF33A2 suffered a severe loss of peripheral CD4+ T cells and
      high acute plasma viremia with development of simian AIDS 9 months after
      inoculation. Sequence analysis identified 25 discreet amino acid changes within
      the V1-V5 regions of the envelope protein when compared with the nonpathogenic
      parental virus. These data indicate that domains within the HIV-1 envelope
      protein are sufficient to define pathogenic potential in the context of the
      SIVmac239 genome.

PMID- 11464141
TI  - Antiretroviral treatment simplification with nevirapine in protease inhibitor
      experienced patients with hiv-associated lipodystrophy: 1-year prospective follow
      up of a multicenter, randomized, controlled study.
AB  - BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to
      maximize treatment compliance without sacrificing potency, at least for drug
      experienced HIV-infected patients currently on regimens containing protease
      inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of
      PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic,
      immunologic, and clinical benefit of switching the PI to nevirapine in patients
      with HIV-associated lipodystrophy and sustained viral suppression before entry in
      the study. DESIGN: Open-labeled, prospective, randomized, multicenter study.
      SETTING: Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One
      hundred six HIV-infected adults with clinically evident lipodystrophy who
      sustained HIV-RNA suppression for at least 6 months with PI-containing
      antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine
      during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS:
      Several virologic and immunologic analyses, standard and specific biochemical
      tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At
      week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of
      patients in Groups A and B, respectively, whereas 74% and 72% of patients had
      viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in
      both groups compared with baseline values, and a significant decrease in
      CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no
      significant changes in anthropometric or body shape measurements were found after
      48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A
      (but not in Group B) compared with baseline values (p <.05), although no
      significant differences were seen between groups at the end of the study.
      Subjects in Group A reported a better quality of life (QOL) index than controls
      (p <.001), with the main reason reported being the greater simplicity of the new
      drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including
      nevirapine, seem to be an effective alternative for PI-experienced patients.
      Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels
      and improve the immunologic response at 48 weeks of follow-up in patients with
      prior sustained virologic suppression. The switch to nevirapine significantly
      improved the lipidic profile in Group A, although there were no differences
      between groups at the end of the study. Additionally, no significant changes were
      seen in terms of lipodystrophy-related body shape changes 1 year after the PI
      substitution. Finally, nevirapine-containing regimens have a simpler dosing
      schedule, and this facilitates high adherence and improves QOL.

PMID- 11464142
TI  - Stavudine versus zidovudine and the development of lipodystrophy.
AB  - The pathogenesis of some components of the lipodystrophy (LD) syndrome might be
      linked to the use of nucleosides. Earlier reports did not compare treatment
      regimens according to the nucleoside backbone. We studied a cohort of individuals
      who did not switch between stavudine and zidovudine. LD was defined to be present
      if one of three criteria was met: self-report by the patient, observation by an
      investigator who had known the patient since commencement of highly active
      antiretroviral therapy (HAART), or examination by a physician masked to therapy.
      The mean duration of therapy was 101 weeks (range: 26-234 weeks). Overall
      prevalence of LD was 48.7%. Lipoatrophy and lipohypertrophy occurred in 33.9% and
      28.7% of patients, respectively. Logistic regression showed four parameters to be
      significantly associated with lipoatrophy: HAART longer than 2 years (p =.002,
      odds ratio [OR] = 4.4, 95% confidence interval [CI]: 1.608-11.965), baseline
      viral load >100,000 copies/ml (p =.004, OR = 4.3, CI: 1.726-11.197), age >40
      years (p =.016, OR = 3.2, CI: 1.247-8.373), and white ethnicity (p =.041, OR =
      5.4, CI: 1.070-28.184). Cholesterol levels of >200 mg/dl at baseline were
      associated with a risk reduction (p =.047, OR = 0.36, CI: 0.130-0.987). Use of
      lipohypertrophy as a dependent variable resulted in a significant association
      with HAART duration (p = 0.028, OR = 2.7, CI: 1.2-6.5) and protease inhibitor use
      (p =.014, OR = 3.8, CI: 1.3-11.2). LD prevalence is similar with both backbones
      using stavudine or zidovudine. This is the first time that baseline cholesterol
      was shown to be significantly associated with lipoatrophy.

PMID- 11464143
TI  - Association between insulin resistance and hepatitis C virus chronic infection in
      HIV-hepatitis C virus-coinfected patients undergoing antiretroviral therapy.
AB  - Insulin resistance (IR) in the context of highly active antiretroviral therapy
      (HAART) is becoming more common in HIV-infected patients. Patients with chronic
      hepatitis C virus (HCV) infection have an increased risk of IR and type 2
      diabetes mellitus. A cross-sectional study was performed to investigate whether
      chronic HCV infection constitutes a risk factor for IR in HIV-HCV-coinfected
      patients undergoing HAART. Inclusion criteria were positive HCV viremia and a
      sustained increase of alanine aminotransferase of at least twice the normal
      value. A total of 29 HIV-HCV patients, 76 HIV patients, and 121 HCV controls were
      tested for IR and body mass index (BMI). IR was measured using the homeostasis
      model assessment. In HIV-HCV and HIV patients, fat redistribution and lipid
      profile were assessed. There was no significant difference in age, CD4 cell
      count, HIV viral load, or duration of HAART between the HIV-HCV and HIV groups.
      HIV-HCV patients and HCV controls had a significant increase in IR when compared
      with HIV patients (0.25 +/- 0.28 and 0.21 +/- 0.34 versus 0.04 +/- 0.37; p =.01
      and p =.003, respectively). Lipoatrophy was observed more frequently in HIV-HCV
      patients in comparison with HIV patients (41% versus 14%; p =.003). In HIV-HCV
      patients, total cholesterol and triglyceride levels were significantly lower than
      in HIV patients. In multivariate analysis, IR, BMI, triglyceride levels, and
      peripheral fat wasting were the independent variables associated with HCV
      infection. Our findings suggest that chronic HCV infection is a significant
      factor associated with the development of metabolic abnormalities and with
      modifications in body composition in HIV patients receiving antiretroviral
      treatment.

PMID- 11464144
TI  - Detrimental effects of continued illicit drug use on the treatment of HIV-1
      infection.
AB  - OBJECTIVE: To identify the effects of substance abuse status (active, former, and
      never) on utilization of highly active antiretroviral therapy (HAART), medication
      adherence, and virologic and immunologic responses to therapy. DESIGN:
      Prospective cohort study of 764 HIV-1-infected patients who attended an urban HIV
      clinic and participated in a standardized interview. MAIN OUTCOME MEASURES: Past
      utilization of HAART, self-reported nonadherence with antiretroviral therapy, and
      changes in HIV-1 RNA level and CD4+ lymphocyte count relative to prior peak and
      nadir, respectively. RESULTS: Forty-four percent of active drug users failed to
      utilize HAART compared with 22% of former drug users and 18% of non-drug users (p
      <.001 for both comparisons). Among participants who were taking antiretroviral
      therapy when interviewed, active drug users were more likely to report medication
      nonadherence (34% vs. 24% of nonusers and 17% of former users), had a smaller
      median reduction in HIV-1 RNA from baseline (0.8 log10 copies/ml vs. 1.7 in
      nonusers and 1.6 in former users), and had smaller median increases in CD4+
      lymphocyte count from baseline (65 cells/mm3 vs. 116 in nonusers and 122 in
      former users) (p <.05 for all comparisons with active users). CONCLUSIONS: Active
      drug use was strongly associated with underutilization of HAART, nonadherence,
      and inferior virologic and immunologic responses to therapy, whereas former drug
      users and non-drug users were similar in all outcomes. Effective strategies are
      needed that integrate HIV-1 and substance abuse treatments.

PMID- 11464145
TI  - A pilot trial of indinavir, ritonavir, didanosine, and lamivudine in a once-daily
      four-drug regimen for HIV infection.
AB  - OBJECTIVE: To evaluate the tolerance, pharmacokinetics, and virologic and
      immunologic outcomes of once-daily indinavir, ritonavir, didanosine, and
      lamivudine in HIV-seropositive individuals. DESIGN: Open-label 24-week pilot
      study. PATIENTS: Ten HIV-seropositive subjects who were either antiretroviral
      naive or minimally experienced with short-term single-or dual-nucleoside therapy
      provided informed consent and were enrolled. All subjects received didanosine
      (400 mg) 30 to 60 minutes before a meal followed by indinavir (1200 mg),
      ritonavir (400 mg), and lamivudine (300 mg) concurrent with the aforementioned
      meal. METHODS: Safety laboratory tests, including a complete blood cell count and
      amylase, lipase, liver transaminase, and nonfasting lipid monitoring as well as
      plasma HIV viral load and CD4+ lymphocyte count, were carried out at monthly
      intervals. Genotyping was performed at baseline. Pharmacokinetic studies for
      indinavir and ritonavir were performed at week 8. RESULTS: Nine of 10 subjects
      completed 24 weeks of therapy. No subject demonstrated primary protease inhibitor
      mutations at baseline. Toxicities experienced by subjects were typically mild and
      consistent with those commonly reported for each of the medications, including
      two cases of hematuria. By week 24, median nonfasting cholesterol and
      triglyceride levels increased by 49% and 108%, respectively. Median baseline
      plasma HIV viral load and CD4+ lymphocyte count were 29,292 (4.47 log10)
      copies/ml and 224 cells/mm3, respectively. Eight of 10 subjects had a plasma HIV
      viral load of <50 copies/ml by week 12. The 2 subjects with a detectable HIV
      viral load reached <50 copies/ml by week 28. Median CD4+ lymphocyte counts
      increased by 193 cells/mm3 at week 24. Indinavir and ritonavir plasma
      concentrations remained above respective inhibitory and effective concentrations
      (IC95 and EC50) (uncorrected for protein binding) throughout the 24-hour dosing
      interval for 6 of 10 and 8 of 10 subjects, respectively. CONCLUSIONS: Our pilot
      study demonstrates excellent virologic suppression despite low minimum protease
      inhibitor concentrations during a dosing interval in some patients and is
      supportive of further study.

PMID- 11464146
TI  - Long-term evaluation of T-cell subset changes after effective combination
      antiretroviral therapy during asymptomatic HIV-infection.
AB  - Demonstration of long-lived HIV-reservoirs resistant to the effects of
      combination antiretroviral therapy raises concern over the ability of treatment
      to maintain long-term beneficial alterations in T-cell subset composition. To
      address this issue, we have examined the effect of antiretroviral therapy on T
      cell subset change during early HIV-infection in a 2-year prospective open-label
      trial composed of treatment-naive asymptomatic HIV-infected patients with CD4+ T
      cell counts > or =400 cells/microl. Therapy consisted of double (zidovudine and
      lamivudine) or triple (zidovudine, lamivudine, and ritonavir) combination
      antiretroviral therapy. Retrospective analysis based on magnitude of viral
      suppression was used to characterize responder and nonresponder groups. Among
      responders, long-term antiretroviral therapy maintained a significant increase in
      numbers of total CD4+, naive CD4+/CD45RA+, and memory CD4+/CD45RO+ T cells. A
      concomitant significant decrease in numbers of memory CD8+/CD45RO+ and both
      activated CD8+/HLA-DR+ and CD8+/CD38+ T cells was also maintained. In contrast,
      long-term antiretroviral therapy among nonresponders led only to a significant
      increase in the numbers of CD4+ T cells and a significant reduction in numbers of
      activated CD8+/HLA-DR+ T cells. The long-term ability of antiretroviral therapy
      during early asymptomatic HIV-infection to maintain reversal of disease-induced T
      cell activation and maturation abnormalities continues to support the concept
      that immunologic advantage is gained by commencing early aggressive
      antiretroviral therapy. Nevertheless, continued management of T-cell subset
      recovery is significantly more effective in the presence of completely suppressed
      viral replication.

PMID- 11464147
TI  - DNA copy number alterations in HIV-positive and HIV-negative patients with
      diffuse large-cell lymphomas.
AB  - Individuals infected with HIV are at increased risk of developing aggressive non
      Hodgkin's lymphoma with a worse prognosis than those similarly afflicted without
      HIV infection. The underlying genetic differences in tumor behavior between these
      two groups are not known. We explored the hypothesis that lymphomas from HIV
      positive individuals have distinct somatic genetic changes that may provide clues
      to the genetic basis of disease progression and outcome. Genome-wide DNA copy
      number alterations (CNAs) in primary tumors from 14 HIV-positive and 11 HIV
      negative patients with diffuse large B-cell lymphoma (DLCL) were quantified using
      comparative genomic hybridization (CGH). Tumors from HIV-positive patients
      displayed fewer regional DNA-CNAs than those from patients who did not have HIV.
      When CNAs were present, they occurred at lower frequency in HIV-positive
      patients. Gains at chromosomes 8q and Xp were the most frequent changes in the
      HIV-negative group, and gains on 2p and 12q were common in the combined HIV
      positive and HIV-negative groups. No alteration was specific to AIDS-related
      DLCL. These data suggest that fewer somatic genomic changes are needed for
      progression to DLCL in HIV-immunocompromised hosts, and that other factors, such
      as reduced immune surveillance, may contribute to neoplastic progression.

PMID- 11464148
TI  - Mismatched human leukocyte antigen alleles protect against heterosexual HIV
      transmission.
AB  - Genetic variation at the human leukocyte antigen (HLA) loci has been shown to be
      an important risk factor for progression to HIV disease, but its significance in
      infection is less well understood. We have investigated its role in HIV
      transmission in a cohort of individuals at risk for heterosexual infection.
      Analysis of over 80 individuals revealed that that the degree of concordance at
      HLA A, B, and DR loci differs significantly between transmitting and
      nontransmitting couples at risk for heterosexual HIV transmission (p <.02),
      suggesting that allogeneic immune responses may confer a degree of protection
      against HIV infection. Analysis of the frequencies of specific alleles at the A,
      B, and DR loci revealed a significantly higher frequency of HLA DR5 among exposed
      uninfected individuals, relative to population controls.

PMID- 11464149
TI  - Who will enroll? Predicting participation in a phase II AIDS vaccine trial.
AB  - BACKGROUND: The problems of underenrollment and selective enrollment may
      undermine AIDS vaccine trials. If prospective study subjects' stated willingness
      to participate (WTP) in hypothetical vaccine trials predicts future enrollment,
      then measuring WTP before recruitment may enhance the enrollment in, and ethics
      of, such trials. METHODS: We prospectively studied changes over an 18-month
      period in the stated WTP in, and knowledge of, a hypothetical AIDS vaccine trial
      among 610 Philadelphia residents at high risk for HIV infection. Of these people,
      499 were subsequently recruited to participate in an actual, phase II AIDS
      vaccine trial. We used multivariable logistic regression and the area under the
      receiver-operating characteristic (ROC) curve to model predictors of actual
      enrollment. RESULTS: Actual enrollment rates were 8.3%, 6.8%, 15.8%, and 29.0%
      among those who had initially said they were "definitely not," "probably not,"
      "probably," and "definitely" willing to participate, respectively (p =.006). The
      area under the ROC curve was 0.65, indicating a modest ability of stated WTP to
      differentiate those who enroll from those who do not. Knowledge of basic vaccine
      trial concepts, though unrelated to enrollment, increased over an 18-month period
      with repeated education sessions (p <.0001), whereas stated WTP declined over
      this same period (p <.0001). CONCLUSION: Although other factors not captured by
      stated WTP may also influence future enrollment, prospectively assessing stated
      WTP may augment the validity of the informed consent process, help prevent
      underenrollment, and clarify the population from which the study sample is drawn.

PMID- 11464150
TI  - Brief report: condom use consistency associated with beliefs regarding HIV
      disease transmission among women receiving HIV antiretroviral therapy.
AB  - OBJECTIVE: To ascertain whether condom use consistency is associated with beliefs
      regarding a decreased likelihood of HIV transmission as a function of taking
      antiretroviral therapy. DESIGN: Cross-sectional analysis of HIV-positive women
      from Brooklyn (NY) enrolled in the Women's Interagency HIV Study (WIHS) who were
      taking any form of antiretroviral therapy at the time of data collection.
      METHODS: Between February and October, 1999, 145 HIV-positive eligible women
      participated in a structured, face-to-face interview. Interviews assessed
      attitudes and behaviors related to antiretroviral therapy and sexual risk
      behavior in the 6 months since a previous study visit. RESULTS: Over three
      fourths of the study sample (77%) disagreed with a statement that being on
      antiretroviral therapy decreases the chances of transmitting HIV to others. After
      controlling for number of sexual partners and HIV serostatus of partners, women
      reporting no association between HIV therapy and disease infectiousness were over
      three times more likely to report consistent condom use (odds ratio [OR], 3.1;
      95% confidence interval [CI], 1.2-8.3; p <.05). CONCLUSIONS: Antiretroviral
      therapy may be associated with increased risk behavior when it is believed that
      regimens may decrease the risk of disease transmission. Education regarding
      potential deleterious consequences of inconsistent condom use should be part of
      ongoing HIV care.

PMID- 11464151
TI  - Deciding where and how to be tested for HIV: what matters most?
AB  - This study examined preferences for specific types of HIV tests as well as for
      test attributes such as cost, counseling, and privacy. A survey was administered
      to 354 clients of public testing services. Nonparametric tests and logistic
      regression were used to compare test preferences and attribute ratings, and to
      assess differences by demographic and risk groups. Nearly two thirds of
      respondents chose a public clinic test as their first choice, whereas 24% chose a
      home self-test, 12% chose a test at a doctor's office, and 1% chose a home
      specimen-collection test. Three attributes (accuracy/timeliness, privacy of test
      disclosure, and linking of test results) were rated equally-and most-important.
      In-person counseling was endorsed as the fourth most important attribute.
      Availability of in-person counseling was the strongest predictor of "loyalty" to
      public clinic tests-a consistent preference for that type of test even when the
      other tests were offered as additional no-cost options. There was also
      substantial interest in home self-tests. The results suggest specific attributes
      of testing that may be particularly important to individuals from diverse
      demographic and risk backgrounds.

PMID- 11464152
TI  - Concurrence of drug users' self-report of current HIV status and serotest
      results.
AB  - This study examines the concurrence of drug users' self-reports of current HIV
      status with serotest results. The analyses are based on data obtained from face
      to-face interviews with 7,256 out-of-treatment injection drug and/or crack users
      in 10 sites that participated in the Cooperative Agreement for AIDS Community
      Based Outreach/Intervention Research Program (funded by the U.S. National
      Institute on Drug Abuse ). Although the degree of concurrence between HIV
      negative individuals' self-reports of their current HIV status and their serotest
      results was high (specificity, 99%), this was not the situation for individuals
      who tested positive for HIV (sensitivity, 44%).

PMID- 11464153
TI  - Cofactors for HIV disease progression in a cohort of homosexual and bisexual men.
AB  - To evaluate cofactors for progression of HIV infection, the authors identified
      370 men with well-defined seroconversion dates and cofactor data among
      participants in the San Francisco City Clinic Cohort (SFCCC). Postseroconversion
      substance use, sexual behavior, and sexually transmitted diseases were assessed
      using multivariate proportional hazards models. Weekly use of hallucinogens
      strongly and independently predicted death (relative hazard [RH], 2.59; 95%
      confidence interval [CI], 1.56-4.28), as well as diagnosis of AIDS; weekly
      cocaine use also predicted mortality. Receptive anal intercourse with ejaculation
      was independently associated with mortality risk (RH, 1.45; 95% CI, 1.02-2.04)
      and AIDS. The associations of accelerated progression with weekly use of
      recreational drugs and unprotected receptive anal intercourse need to be
      confirmed in other prospective cohorts.

PMID- 11464154
TI  - Presence of genotypic resistance to antiretroviral drugs in a cohort of therapy
      naive HIV-1-infected Italian patients.

PMID- 11464155
TI  - Risk factors for hepatotoxicity in patients treated with highly active
      antiretroviral therapy.

PMID- 11464156
TI  - Low prevalence of cardiac abnormalities in an HIV-seropositive population on
      antiretroviral combination therapy.

PMID- 11464157
TI  - The Boeing prospective study and beyond.
AB  - STUDY DESIGN: The Boeing prospective study was reviewed. The Boeing prospective
      study, comprising two articles, was a large field study that explored why workers
      would or would not report occupational back pain problems. OBJECTIVES: The most
      immediate objective was to determine the extent to which conclusions drawn from
      the Boeing prospective study withstand critical examination. The ultimate purpose
      of this review was to develop guidelines for field studies of back pain in
      industry. SUMMARY OF BACKGROUND DATA: For more than a century, researchers have
      noted great variability among individuals in the reporting of back pain, but the
      explanations posed for this variability have been inconsistent. Because findings
      gain credibility roughly to the extent that they bear on the world outside the
      laboratory, field studies in particular hold great potential for clarifying the
      underlying explanation for individual variability in back pain reporting. The
      Boeing prospective study was a large and ambitious field study that examined this
      issue. METHODS: The Boeing prospective study was examined through the lens of
      research conducted since it was published. The review used both the
      methodological and substantive literature. RESULTS: The Boeing prospective study,
      based on a minority of workers originally solicited to participate in it (33
      41%), accounted for 7% of the variation in why workers would or would not report
      a back pain problem. A number of issues that may have biased its results toward
      the null are examined. CONCLUSIONS: The highlighting of the Boeing prospective
      study's limitations may be instructive not so much to criticize this one
      particular study but, rather, to anticipate problems that in general may be
      encountered in field studies of back pain in industry. Looking beyond the Boeing
      prospective study, the following guidelines for the conduct of such studies may
      be proposed: 1) Study designs should be based on explanations from which testable
      hypotheses may be derived; 2) Subgroups within the more general category of "back
      pain" should be delineated; 3) Both occupational exposures and psychosocial
      factors should be entered into the analysis; 4) Factors not apparent at the
      workplace should be considered; 5. Abstracts of articles should be carefully
      crafted.

PMID- 11464158
TI  - Staged spinal cord decompression through posterior approach for thoracic
      myelopathy caused by ossification of posterior longitudinal ligament.
AB  - STUDY DESIGN: Prospective clinical study of the effect of staged elimination of
      anatomic factors inhibiting posterior shift of the thoracic spinal cord on the
      degree of posterior shift of the thoracic spinal cord and its significance in
      augmenting the safety of ossification of posterior longitudinal ligament (OPLL)
      manipulation in thoracic OPLL myelopathy. OBJECTIVES: To develop a comprehensive
      method that enables safe and sufficient decompression of the spinal cord for
      thoracic OPLL myelopathy. SUMMARY OF BACKGROUND DATA: Decompression of the spinal
      cord by direct manipulations of thoracic OPLLs, via either anterior or posterior
      approach, caused some iatrogenic catastrophic spinal cord injuries, and methods
      to prevent such injuries during surgery have not yet been developed. METHODS:
      Procedures of elimination of anatomic factors inhibiting posterior shift of the
      thoracic spinal cord were performed in stages at intervals of between 1 month and
      11 years depending on patients' neurologic status. The first stage operation
      consisted of extensive cervicothoracic laminoplastic decompression with or
      without posterior longitudinal durotomy, and if the decompression were
      insufficient, measures for OPLL-spinal cord separation with or without OPLL
      manipulation were added. RESULTS: All 17 patients with thoracic OPLL myelopathy
      showed improvements of neurology comparable with those with successful anterior
      approaches after decompression. The mean follow-up period was 42 months (range 6
      101 months). Neurologic improvements persisted for the entire follow-up period in
      all patients except one patient who developed arachnoid cyst compressing the
      dorsum of the once-decompressed spinal cord 30 months after surgery. CONCLUSIONS:
      Staged posterior decompression to eliminate anatomic factors inhibiting posterior
      shift of the thoracic spinal cord is the safest and the most reliable method of
      spinal cord decompression to treat thoracic OPLL myelopathy, so far. However,
      long-term results are required before the methods can be established.

PMID- 11464159
TI  - Initial outcome and efficacy of "kyphoplasty" in the treatment of painful
      osteoporotic vertebral compression fractures.
AB  - STUDY DESIGN: An Institutional Review Board-approved Phase I efficacy study of
      inflatable bone tamp usage in the treatment of symptomatic osteoporotic
      compression fractures. OBJECTIVES: To evaluate the safety and efficacy of
      inflatable bone tamp reduction and cement augmentation, "kyphoplasty," in the
      treatment of painful osteoporotic vertebral compression fractures. SUMMARY OF
      BACKGROUND DATA: Osteoporotic compression fractures can result in progressive
      kyphosis and chronic pain. Traditional treatment for these patients includes bed
      rest, analgesics, and bracing. Augmentation of vertebral compression fractures
      with polymethylmethacrylate, "vertebroplasty," has been used to treat pain. This
      technique, however, makes no attempt to restore the height of the collapsed
      vertebral body. Kyphoplasty is a new technique that involves the introduction of
      inflatable bone tamps into the vertebral body. Once inflated, the bone tamps
      restore the vertebral body back toward its original height while creating a
      cavity that can be filled with bone cement. PATIENTS AND METHODS: Seventy
      consecutive kyphoplasty procedures were performed in 30 patients. The indications
      included painful primary or secondary osteoporotic vertebral compression
      fractures. Mean duration of symptoms was 5.9 months. Symptomatic levels were
      identified by correlating the clinical data with MRI findings. Perioperative
      variables and bone tamp complications or issues were recorded and analyzed.
      Preoperative and postoperative radiographs were compared to calculate the
      percentage height restored. Outcome data were obtained by comparing preoperative
      and latest postoperative SF-36 data. RESULTS: At the completion of the Phase I
      study there were no major complications related directly to use of this technique
      or use of the inflatable bone tamp. In 70% of the vertebral bodies kyphoplasty
      restored 47% of the lost height. Cement leakage occurred at six levels (8.6%).SF
      36 scores for Bodily Pain 11.6-58.7, (P = 0.0001) and Physical Function 11.7
      47.4, (P = 0.002) were among those that showed significant improvement.
      CONCLUSIONS: The inflatable bone tamp was efficacious in the treatment of
      osteoporotic vertebral compression fractures. Kyphoplasty is associated with
      early clinical improvement of pain and function as well as restoration of
      vertebral body height in the treatment of painful osteoporotic compression
      fractures.

PMID- 11464162
TI  - Re: correlation between a positive Hoffmann's reflex and cervical pathology in
      asymptomatic individuals.

PMID- 11464163
TI  - Useful information on the prognosis for neck pain occurring after a rear-end
      motor vehicle collision.

PMID- 11464164
TI  - Re: reduction and fixation of sacroiliac joint dislocation by the combined use of
      S1 pedicle screws and the Galveston technique.

PMID- 11464167
TI  - The next meeting is not for me!

PMID- 11464170
TI  - Myths and realities about E-health.

PMID- 11464169
TI  - Polypharmacy, herbal therapies, and elders.

PMID- 11464171
TI  - Community case management outcomes.

PMID- 11464172
TI  - The Case Report: a newsletter from the Case Management Society of America:
      President's message.

PMID- 11464173
TI  - Case management in the bliss zone: overcoming ethical issues to advocate for a
      catastrophic patient.

PMID- 11464174
TI  - Professional integrity: a commentary on "Case Management in the bliss Zone".

PMID- 11464175
TI  - Patient education: a collaborative process.

PMID- 11464176
TI  - Dispelling rumors about long-term acute care hospitals.

PMID- 11464177
TI  - Direct to consumer case management.

PMID- 11464178
TI  - Panniculitis. Part I. Mostly septal panniculitis.
AB  - The panniculitides represent a group of heterogeneous inflammatory diseases that
      involve the subcutaneous fat. The specific diagnosis of these diseases requires
      histopathologic study because different panniculitides usually show the same
      clinical appearance, which consists of subcutaneous erythematous nodules on the
      lower extremities. However, the histopathologic study of panniculitis is
      difficult because of an inadequate clinicopathologic correlation, and the
      changing evolutionary nature of the lesions means that biopsy specimens are often
      taken from late-stage lesions, which results in nonspecific histopathologic
      findings. In addition, large-scalpel incisional biopsies are required. However,
      we believe that by obtaining appropriate biopsy specimens and with adequate
      clinicopathologic correlation, a specific diagnosis may be rendered in most cases
      of panniculitis. It must be accepted that all panniculitides are somewhat mixed
      because the inflammatory infiltrate involves both the septa and lobules; however,
      in general the differential diagnosis between a mostly septal and a mostly
      lobular panniculitis is straightforward at scanning magnification. Mostly septal
      panniculitides with vasculitis include leukocytoclastic vasculitis involving the
      small blood vessels of the septa; superficial thrombophlebitis resulting from
      inflammation and subsequent thrombosis of large veins of the septa; and cutaneous
      polyarteritis nodosa, which is a vasculitis involving arteries and arterioles of
      the septa of subcutaneous fat with few or no systemic manifestations. Often
      septal panniculitides with no vasculitis are the consequence of dermal
      inflammatory processes extending to the subcutaneous fat, such as necrobiosis
      lipoidica, scleroderma, subcutaneous granuloma annulare, rheumatoid nodule, and
      necrobiotic xanthogranuloma. However, in other cases, the inflammatory process is
      primarily located in the fibrous septa of the subcutis with or without
      involvement of the overlying dermis. The most frequently seen septal panniculitis
      is erythema nodosum, which, in fully developed lesions, is characterized
      histopathologically by Miescher's radial granulomas in the septa.

PMID- 11464179
TI  - A randomized trial of the efficacy of a new micronized formulation versus a
      standard formulation of isotretinoin in patients with severe recalcitrant nodular
      acne.
AB  - BACKGROUND: Isotretinoin is very frequently the drug of choice for the management
      of severe recalcitrant nodular acne. Recently, a new micronized and more
      bioavailable formulation of isotretinoin has been developed that permits once
      daily administration in lower doses than usually used with standard isotretinoin
      (Accutane), regardless of whether it is taken with or without food. OBJECTIVE:
      Our purpose was to determine whether micronized isotretinoin and standard
      isotretinoin are clinically equivalent. METHODS: In this multicenter, double
      blind, double-dummy study, 600 patients with severe recalcitrant nodular acne
      were treated with either 0.4 mg/kg of micronized isotretinoin once daily without
      food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses
      with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both
      treatment groups in this well-controlled clinical trial experienced an equivalent
      reduction in the number of total nodules (facial plus truncal). In addition, an
      equivalent proportion of patients achieved 90% clearance of the total number of
      nodules. Both formulations had similar results for other efficacy variables.
      CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of
      isotretinoin under fasted conditions is clinically equivalent to the standard
      twice-daily formulation under fed conditions in the treatment of severe
      recalcitrant nodular acne.

PMID- 11464180
TI  - Safety of a new micronized formulation of isotretinoin in patients with severe
      recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin
      with standard isotretinoin.
AB  - BACKGROUND: Isotretinoin is a very effective drug for treating severe
      recalcitrant nodular acne. A new micronized formulation of isotretinoin has been
      shown to be clinically equivalent to standard isotretinoin with improved
      bioavailability and minimal food effect. The safety profile of the micronized
      formulation has not been described previously. OBJECTIVE: The objective of this
      article is to report the incidence and intensity of adverse events found in a
      comparative, double-blind efficacy study that showed clinical equivalence of the
      new micronized formulation of isotretinoin and the standard isotretinoin
      formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant
      nodular acne were treated with micronized isotretinoin (n = 300) under fasted
      conditions or standard isotretinoin (n = 300) under fed conditions. One cohort
      received single daily doses of 0.4 mg/kg of micronized isotretinoin without food
      and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two
      divided doses with food. Adverse events were monitored during 20 weeks of drug
      therapy. RESULTS: The proportion of adverse events in most body systems was
      generally lower in patients receiving micronized isotretinoin than in those
      receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to
      have a safety profile similar to that of standard isotretinoin and to carry a
      lower risk of mucocutaneous events and hypertriglyceridemia.

PMID- 11464181
TI  - Complete molecular remission during biologic response modifier therapy for Sezary
      syndrome is associated with enhanced helper T type 1 cytokine production and
      natural killer cell activity.
AB  - BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a clonally derived, skin-invasive
      malignancy of CD4(+) T lymphocytes with the phenotype of mature helper T cells.
      Advancing stages of CTCL are associated with depressed cell-mediated immunity,
      increased production of T helper type 2 cytokines and decreased levels of T
      helper type 1 cytokines. OBJECTIVE: Our purpose was to evaluate the cytokine
      secretion pattern and cell-mediated cytotoxicity in peripheral blood mononuclear
      cells of patients with Sezary syndrome in relation to the presence of the
      malignant clone. METHODS: Serial polymerase chain reaction for the T-cell
      receptor-beta or T-cell receptor-gamma gene rearrangement was used to determine
      the presence of the malignant clone. Enzyme-linked immunosorbent assays were used
      to determine the levels of interleukin 4 and interferon gamma produced by the
      peripheral blood mononuclear cells from the patients with Sezary syndrome.
      RESULTS: We demonstrate 3 cases of Sezary syndrome with typically suppressed cell
      mediated cytotoxicity, elevated production of interleukin 4, and depressed
      production of interferon gamma by their peripheral blood mononuclear cells before
      institution of therapy with biologic response modifier therapy. In all 3 cases
      after clinical and molecular remission, we observed striking immunologic changes,
      including an increase in levels of natural killer cell activity and interferon
      gamma production and decreased production of interleukin 4. CONCLUSIONS: The
      observation that the cytokine secretion pattern by peripheral blood mononuclear
      cells from 3 patients with Sezary syndrome normalized with the disappearance of
      the malignant clone from the peripheral blood suggests that the malignant T cells
      account for the aberrant cytokine production. Moreover, the aberrant cytokine
      production may be the cause for suppression of cell-mediated immunity seen in
      advancing stages of CTCL.

PMID- 11464182
TI  - Histologic features of actinic keratoses in solid organ transplant recipients and
      healthy controls.
AB  - BACKGROUND: Squamoproliferative lesions are common in patients who are
      immunosuppressed, particularly in recipients of solid organ transplants.
      Histologic features in such biopsy specimens may differ from those of otherwise
      healthy patients. Actinic keratoses (AKs) in transplant recipients may possess
      pathologic characteristics that suggest that they arose in an immunosuppressed
      host. OBJECTIVE: We evaluated 30 randomly selected AKs from 25 recipients of
      solid organ transplants and compared their histologic features to those of 50 AKs
      from 45 patients who were not immunosuppressed. METHODS: Tissue samples were
      categorized by sex, patient age, and site of biopsy. Sixteen separate histologic
      criteria were evaluated in a blinded fashion in each specimen. Statistical
      analysis was performed between the two groups with and without controlling for
      the age of the patient. RESULTS: The transplant group was significantly younger
      (54.8 years) than the nontransplant group (70.0) and contained more men (88%)
      than women (51%). AKs from transplant recipients were statistically more likely
      to demonstrate bacterial colonization, confluent parakeratosis, hyperkeratosis,
      increased mitotic activity, and verrucous changes. After controlling for age
      only, hyperkeratosis failed to be more prevalent in the transplant group.
      CONCLUSION: Certain histopathologic features are more common in AKs of
      immunosuppressed transplant recipients and may be used to distinguish between
      those removed from otherwise healthy persons.

PMID- 11464183
TI  - Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A
      multicenter, randomized, placebo-controlled trial.
AB  - BACKGROUND: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the
      US population. Although the disease is self-limiting in persons with a healthy
      immune response, patients seek treatment because of the discomfort and visibility
      of a recurrent lesion. OBJECTIVE: Our purpose was to determine whether docosanol
      10% cream (docosanol) is efficacious compared with placebo for the topical
      treatment of episodes of acute HSL. METHODS: Two identical double-blind, placebo
      controlled studies were conducted at a total of 21 sites. Otherwise healthy
      adults, with documented histories of HSL, were randomized to receive either
      docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or
      erythema stage of an episode. Treatment was administered 5 times daily until
      healing occurred (ie, the crust fell off spontaneously or there was no longer
      evidence of an active lesion) with twice-daily visits. RESULTS: The median time
      to healing in the 370 docosanol-treated patients was 4.1 days, 18 hours shorter
      than observed in the 367 placebo-treated patients (P =.008; 95% confidence
      interval [CI]: 2, 22). The docosanol group also exhibited reduced times from
      treatment initiation to (1) cessation of pain and all other symptoms (itching,
      burning, and/or tingling; P =.002; 95% CI: 3, 16.5); (2) complete healing of
      classic lesions (P =.023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or
      soft crust stage of classic lesions (P <.001; 95% CI: 8, 25). Aborted episodes
      were experienced by 40% of the docosanol recipients versus 34% of placebo
      recipients (P =.109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with
      docosanol were mild and similar to those with placebo. CONCLUSION: Docosanol
      applied 5 times daily is safe and effective in the treatment of recurrent HSL.
      Differences in healing time compared favorably with those reported for the only
      treatment of HSL that has been approved by the Food and Drug Administration.

PMID- 11464184
TI  - Dense inflammation does not mask residual primary basal cell carcinoma during
      Mohs micrographic surgery.
AB  - BACKGROUND: Areas of dense inflammation are commonly removed during Mohs
      micrographic surgery for basal cell carcinoma because of the concern that they
      may mask areas of tumor. OBJECTIVE: Our purpose was to determine whether
      inflammation masks tumor during Mohs surgery for primary basal cell carcinoma.
      METHODS: Twenty-five consecutive cases of primary basal cell carcinoma with areas
      of dense inflammation encountered during Mohs surgery were sectioned and stained
      with hematoxylin and eosin and Ber-EP4. RESULTS: In no cases did the dense
      inflammation mask residual tumor. CONCLUSION: Dense inflammation does not mask
      primary basal cell carcinoma during Mohs surgery and should be carefully
      evaluated before additional surgery is performed.

PMID- 11464185
TI  - Facial "glomangiomas": large facial venous malformations with glomus cells.
AB  - BACKGROUND: "Glomangiomas" are benign cutaneous vascular lesions consisting of
      convoluted, abnormally formed venous channels lined by cuboidal and oval
      epithelioid, alpha-actin-positive, glomus cells. Three different clinical
      variants of glomangioma have been recognized: solitary, multiple, and nodular, or
      plaquelike. Inheritable forms are common. OBJECTIVE: We describe in 7 patients (2
      of them having a familial glomangiomatosis) the rare facial location of
      glomangiomas to differentiate this type from common facial venous malformation
      (VM). METHODS: We analyzed clinical data (photographs), course, investigations
      (computed tomographic scans in 4 patients, magnetic resonance imaging in 6,
      arteriography in 2, direct puncture phlebography in 4, and pathologic
      examinations in all 7), and outcome with treatment. RESULTS: Lesions were soft,
      composed of multiple nodules, confluent and plaquelike, deep blue or blue-to
      purple, sometimes sagging, one-sided in a cheek, extending to the lips in 5
      patients, to the chin in 4, and to the lower eyelid in 4. They were poorly
      compressible, a finding different from common facial VMs. In a young man
      extensive back involvement was associated. Among radiologic investigations, only
      magnetic resonance imaging after gadolinium enhancement offered some differential
      features with common VMs. However, histopathologic examination clarified the
      differential diagnosis: although the large tortuous venous channels were
      reminiscent of capillary-venous malformation, in many vessels the walls contained
      one or several rows of glomus cells. CONCLUSION: Multiple plaquelike facial
      "glomangiomas" mimic a common venous malformation because of their blue hue.
      However, with experience, one can clinically recognize them, and their pathologic
      aspect is distinctive. Management should differ slightly from that for common
      facial VM because sclerotherapy has proven to be less effective. Therefore
      surgical treatment is the only helpful therapeutic option.

PMID- 11464186
TI  - Black spot poison ivy: A report of 5 cases and a review of the literature.
AB  - Black-spot poison ivy dermatitis is a rare manifestation of a common condition.
      It occurs on exposure to the resins of the plants of the Rhus family also known
      as Toxicodendron. We describe 5 patients with black deposits on their skin and
      clothing after contact with poison ivy and review the literature reflecting
      different aspects of this phenomenon including clinical presentation, histologic
      findings, and historical background.

PMID- 11464187
TI  - Dermatology in primary care: Prevalence and patient disposition.
AB  - BACKGROUND: Cutaneous disease is commonly encountered in primary care. The
      frequency of patients presenting to primary care physicians with skin disease and
      their eventual disposition is not well studied. OBJECTIVE: The purpose of this
      study was to determine the prevalence of patients seen with skin disease in a
      primary care setting and the likelihood of their referral to a dermatologist. The
      impact the primary care provider had on the quality of skin care was also
      examined. METHODS: A retrospective chart review was performed of patients seen
      during a 2-year period at a general medicine clinic within the University of
      Miami and upon referral to a University of Miami dermatology office. Data were
      obtained on the prevalence of skin disease, dispositions of referral, diagnoses
      made, and procedures performed. RESULTS: During a 2-year period, 36.5% of
      patients who presented to their primary care physician had at least one skin
      problem. Of 208 patients with skin disease, in 58.7% (122/208) it was their chief
      complaint. A wide range of diagnoses were made by the primary care physician,
      with a limited number of diagnostic procedures performed. Of the 37.5% of
      patients referred to a dermatologist, 68% were referred on initial evaluation.
      Diagnoses made by the primary care physician were concordant with that made by
      the dermatologists 57% of the time. CONCLUSION: Patients frequently see their
      primary care physician for skin disease. A large percentage are referred to
      dermatologists, often for a biopsy of a suspect lesion, to confirm a suspected
      diagnosis, or to establish a diagnosis of lesions of unknown origin.

PMID- 11464188
TI  - Treatment of cicatricial pemphigoid with mycophenolate mofetil as a steroid
      sparing agent.
AB  - BACKGROUND: Cicatricial pemphigoid (CP) is a rare autoimmune bullous disease that
      affects the skin and mucous membranes. It commonly ends by serious complications
      such as blindness, stenosis, and stricture formation and is difficult to treat.
      Mycophenolate mofetil has been reported to be effective in the treatment of
      pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid either as
      monotherapy or as a steroid-sparing agent. OBJECTIVE: Our purpose was to evaluate
      the effectiveness of mycophenolate mofetil as a steroid-sparing agent in treating
      patients with CP. METHODS: Three patients with CP were treated with mycophenolate
      mofetil and prednisolone. RESULTS: All 3 patients responded very well to the
      therapy. None of them showed relapse of the disease for a follow-up period of 6
      to 14 months after complete cessation of mycophenolate mofetil and prednisolone.
      No side effects were seen. CONCLUSION: Mycophenolate mofetil appears to be a safe
      and effective steroid-sparing agent in the treatment of CP.

PMID- 11464189
TI  - Primary cutaneous malignant melanoma and its precursor lesions: diagnostic and
      therapeutic overview.
AB  - During the past few decades, scientific data relating to melanoma have
      flourished. New information regarding acquired nevi, dysplastic nevi (atypical
      nevi), and congenital nevi has given us a better understanding of these precursor
      lesions and their relationships to malignant melanoma. The roles of laboratory
      testing, photography, and newer diagnostic tools (eg, epiluminescence) to
      evaluate patients for melanoma or precursor lesions have fallen under close
      scrutiny. Traditional surgical therapeutic interventions continue to be replaced
      by less aggressive protocols based on prospective randomized studies. Many new
      interventions such as sentinel lymph node procedures are currently being
      evaluated at research/referral centers around the world. We present clinicians
      with an evidence-based summary of the current literature with regard to primary
      cutaneous melanoma, its diagnosis, precursor lesions, and therapy.

PMID- 11464190
TI  - Surgical Pearl: A flat plastic cylinder derived from a disposable syringe
      effectively achieves hemostasis in carbon dioxide laser surgery.

PMID- 11464191
TI  - Treatment of severe congenital erythropoietic porphyria by bone marrow
      transplantation.
AB  - Congenital erythropoietic porphyria (CEP), which is the result of a deficiency of
      uroporphyrinogen (URO) III synthase activity, is the most disfiguring porphyria
      in humans. Various methods of treatment have been used to treat CEP with varying
      success, including erythrocyte transfusion, hydroxyurea, and splenectomy. The
      only treatment that corrects the enzymatic defect resulting in a cure is bone
      marrow/stem cell transplantation, which has been reported previously in only 5
      patients worldwide. We describe the first patient with CEP who underwent
      successful bone marrow transplantation performed in the United States and review
      the therapeutic options in the management of this challenging type of porphyria.

PMID- 11464192
TI  - Microcystic adnexal carcinoma: First reported case in an African American man.
AB  - Microcystic adnexal carcinoma (MAC) is a relatively uncommon adnexal neoplasm
      that can display aggressive local invasion. MAC occurs most commonly on the
      central part of the face and can be clinically asymptomatic with a benign
      appearance. We describe the first reported case of MAC in an African American man
      who was treated by Mohs micrographic surgery.

PMID- 11464193
TI  - Interstitial granulomatous dermatitis with cutaneous cords and arthritis: a
      disorder associated with autoantibodies.
AB  - Interstitial granulomatous dermatitis with arthritis is a new entity
      characterized by linear or arciform subcutaneous cords. We describe a patient
      presenting with typical cutaneous lesions extending from the anterior and
      posterior part of the axillae to the flank. The lesions had been present for 6
      years with flares and remission. Histopathologic examination revealed a bandlike
      infiltrate of histiocytes in the reticular dermis with focal areas of palisading
      around necrotic collagen bundles. A few atypical histiocytes were also present.
      As previously described, it was associated with serologic findings of an
      autoimmune disease, especially high titers of anti-DNA antibodies. The possible
      inclusion of the interstitial granulomatous dermatitis in the continuous spectrum
      of the palisaded neutrophilic and granulomatous dermatitis of immune complex
      disease is also discussed.

PMID- 11464194
TI  - Cerebrotendinous xanthomatosis.
AB  - Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid-storage
      disease caused by mutations in the sterol 27-hydroxylase gene. The accumulation
      of cholestanol in various tissues characterizes this disease. Diagnosis is based
      on determination of urinary bile alcohols. Therapy with chenodeoxycholic acid may
      arrest the progression of the disease. A 55-year-old woman presented with a
      slowly progressive paraparesia and two firm subcutaneous tumors over the knees.
      Her medical history revealed difficulty in standing and walking since infancy,
      bilateral juvenile cataracts, and mental retardation. Histopathologic examination
      of one subcutaneous tumor was consistent with tendinous xanthoma. Substantial
      elevation of urinary bile alcohols confirmed the diagnosis. Treatment with oral
      chenodeoxycholic acid was started, with only mild improvement of spasticity.
      Recognition of tendon xanthomas in a young patient with neurologic symptoms or
      cataracts (or both) is crucial to start early treatment and to avoid irreversible
      neurologic sequelae.

PMID- 11464195
TI  - Treatment of epidermodysplasia verruciformis with a combination of acitretin and
      interferon alfa-2a.
AB  - Epidermodysplasia verruciformis (EV) is an autosomal recessive disease
      characterized by the lifelong eruption of disseminated verrucae-like lesions.
      Numerous treatment modalities have been used to treat EV without benefit.
      Recently, retinoid and interferon therapies have been found to be of value in the
      treatment of EV. We present a case of EV that was treated with a combination of
      acitretin and interferon alfa-2a.

PMID- 11464196
TI  - Celecoxib-induced Sweet's syndrome.
AB  - Sweet's syndrome and related neutrophilic dermatoses have been associated with a
      variety of medications. Celecoxib is a new cyclo-oxygenase-2 inhibitor recently
      approved for arthritis. We describe a 57-year-old man who experienced tender
      pustulopapular lesions on the dorsal aspects of the hands, neck, and legs 1 week
      after starting celecoxib. Histopathologic examination of the lesion showed a
      diffuse dermal neutrophilic infiltrate, edema of the papillary dermis, spongiform
      pustules, and no leukocytoclastic vasculitis. These findings were consistent with
      Sweet's syndrome. Without realizing a possible association, the patient
      rechallenged himself with a second course of the medication, which resulted in a
      rapid exacerbation of his lesions. After discontinuing the medication for the
      second time, the patient has had complete clearing of his lesions. To our
      knowledge, this is the first report of Sweet's syndrome associated with this new
      class of nonsteroidal anti-inflammatory drugs.

PMID- 11464197
TI  - Early experience with sentinel lymph node mapping for Merkel cell carcinoma.
AB  - Merkel cell or cutaneous neuroendocrine carcinoma is a malignant tumor with a
      propensity toward local and systemic recurrence. A new surgical technique,
      intraoperative lymphatic mapping and selective sentinel lymph node dissection
      (SSLND), has been demonstrated to have a high predictive value for the detection
      of metastatic disease in the regional lymphatic basin in cutaneous melanoma. The
      use of this technology may be particularly useful to accurately stage patients
      with Merkel cell carcinoma (MCC) because this tumor has a frequent propensity
      toward regional nodal metastases. Intraoperative lymphatic mapping and SSLND were
      performed on 6 patients with biopsy-proven MCC. Three patients with MCC had
      positive disease in the sentinel lymph node(s). SSLND is a feasible technique
      with minimal procedural morbidity to detect clinically occult disease in patients
      with MCC.

PMID- 11464198
TI  - Merkel cell carcinoma in the setting of HIV infection.
AB  - Merkel cell carcinoma has been found to have an increased incidence among
      immunosuppressed patients, specifically organ transplant recipients receiving
      immunosuppressive therapy. HIV similarly depresses the immune response of
      infected persons. We report a case of Merkel cell carcinoma (MCC) in an HIV
      infected patient who died from liver metastases 2 years after his tumor was
      diagnosed. The purpose of this report is to describe the possible relationship
      between HIV and MCC and to emphasize the importance of early diagnosis and
      aggressive management of MCC.

PMID- 11464199
TI  - Patch testing discordance alert: false-negative findings with rubber additives
      and fragrances.
AB  - From July 1996 through June 1998, the North American Contact Dermatitis Group
      evaluated 318 patients for suspected contact dermatitis by patch testing
      simultaneously with Finn Chambers and the T.R.U.E. Test allergen system.
      Discrepancies between the two systems were found in some of the results,
      particularly with fragrance and rubber allergens. These results suggest that
      positive reactions to fragrance, thiuram, and carba mix allergens may be missed
      if the T.R.U.E. Test is used alone.

PMID- 11464200
TI  - Drug-induced cutaneous lupus erythematosus, a distinct syndrome that is
      frequently unrecognized.

PMID- 11464201
TI  - Management of cutaneous T-cell lymphoma: The future is here.

PMID- 11464202
TI  - "Invisible" mycosis fungoides?

PMID- 11464203
TI  - Invisible mycosis fungoides: a new case.

PMID- 11464204
TI  - Ursodeoxycholic acid causing exacerbation of dermatitis herpetiformis.

PMID- 11464205
TI  - Tinea capitis of childhood: incidence and pathogenetic role of Trichophyton
      tonsurans in Central Europe.

PMID- 11464207
TI  - Lichenoid chronic graft-versus-host disease-like acrodermatitis induced by
      hydroxyurea.

PMID- 11464208
TI  - Photodistributed felodipine-induced facial telangiectasia.

PMID- 11464209
TI  - Stroke treatment enters the Fas lane.

PMID- 11464210
TI  - Till death do us part.

PMID- 11464211
TI  - In an adhesion dependent human gastric adenocarcinoma cell line, integrin
      ligation without adhesion rescues from anoikis but is not sufficient for cell
      cycle progression.
AB  - STAD cells are the adherent parental apoptotic line from which two sublines were
      cloned that differed in their response to suspended culturing conditions, one
      clone STAD.APO is apoptotic and the other STAD.ARR goes into cell cycle arrest.
      Using this system we have found that the addition of soluble collagen can rescue
      STAD and STAD.APO cells from anoikis, and it can also affect STAD.ARR cells by
      overcoming the suspension induced cell cycle arrest. In contrast, when cells were
      cultured with a soluble anti-beta1 integrin mAb 33B6, the apoptotic clones again
      were rescued from anoikis, but the cell cycle arresting clone remained quiescent.
      This result was somewhat surprising as it is generally accepted that cytoskeletal
      rearrangements that accompany integrin mediated adhesion and cell shape changes
      are required for the abrogation of anoikis, and it was unexpected that
      differences in the mechanism used for integrin triggering would yield variable
      results on growth regulation. This observation led us to further examine whether
      the addition of a monovalent anti-beta1 integrin agent could produce similar
      results as intact mAb. Therefore we employed Fab fragments of 33B6 in our
      culturing assay and found that indeed monovalent binding was capable of saving
      STAD and STAD.APO cells from anoikis but did not have an effect on STAD.ARR
      cells. Therefore in this study we have observed that integrin mediated dependent
      survival can occur by mere ligation of the beta1 integrin subunit, but that cell
      cycle arrest due to suspended conditions can not. Thus integrins can play
      differential roles in cell fate decisions and mediate these effects by different
      mechanisms.

PMID- 11464212
TI  - Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in
      stroke.
AB  - Stroke is the third most common cause of death in the Western world. The
      mechanisms of brain damage in the affected areas are largely unknown. Hence,
      rational treatment strategies are limited. Previous experimental evidence
      suggested that cerebral lesions were less prominent in CD95 (APO-1/Fas)-deficient
      (lpr) than in wild-type mice. Additional results strongly suggested that the CD95
      ligand (CD95L) was a major cause of neuronal autocrine suicide in the penumbra.
      These data and the assumption that death-receptor systems might determine stroke
      related damage in the brain prompted us to examine these systems in in vitro and
      in vivo models of ischemia. We showed that hybrids of TNF-deficient and gld mice
      were strongly resistant towards stroke-induced damage. To determine the mechanism
      of action of TNF and CD95L, we separately investigated their influence on primary
      ischemic death and secondary inflammatory injury. Inhibition of both TNF and
      CD95L in vitro prevented death of primary neurons induced by oxygen-glucose
      deprivation and reperfusion. The recruitment of inflammatory cells to the
      ischemic hemisphere was abrogated in the absence of both TNF and CD95L.
      Significantly, mice injected with a mixture of neutralizing anti-TNF and anti
      CD95L antibodies 30 min after induction of stroke showed a marked decrease in
      both infarct volumes and mortality. Accordingly, the locomotor performance of
      these animals was not significantly impaired in comparison to sham-operated
      animals. These data reveal that inhibition of TNF and CD95L blocks stroke-related
      damage at two levels, the primary ischemic and the secondary inflammatory injury.
      These results offer new approaches in stroke treatment.

PMID- 11464213
TI  - Functional characterization of Fas ligand on tumor cells escaping active specific
      immunotherapy.
AB  - Mice transgenic for the rat HER-2/neu oncogene (rNeu-TG) developed spontaneous
      breast tumors that can escape a rNeu-specific immune response induced by active
      specific immunotherapy (ASI). The ability of these escape tumors to grow appeared
      to be due to upregulation of the Fas ligand (Fas-L) molecule. In an effort to
      develop tools for the better elucidation of the role of Fas-L and other
      regulatory mechanisms in tumor escape, we established cell lines derived from
      escape tumors. These tumor cell lines retained MHC class I, rNeu and Fas-L
      expression in vitro and formed tumors in vaccinated mice. Tumor growth was
      accompanied by permanent Fas-L expression in vivo, both in vaccinated and control
      vaccinated mice, indicating that these cells have acquired constitutive Fas-L
      expression. Moreover, these cells induced target cell apoptosis in vitro. Thus,
      these cells represent a unique tool to elucidate the importance of Fas-L
      expressed by tumors that escaped efficient systemic immune responses.

PMID- 11464214
TI  - An apoptosis signaling pathway induced by the death domain of FADD selectively
      kills normal but not cancerous prostate epithelial cells.
AB  - The adaptor protein FADD directly, or indirectly via another adaptor called
      TRADD, recruits caspase 8 to death receptors of the tumor necrosis factor
      receptor family. Consequentially, a dominant-negative mutant (FADD-DN, which
      consists only of the FADD death domain) that binds to receptors but cannot
      recruit caspase 8 has been widely used to inhibit apoptosis by various stimuli
      that work via death receptors. Here, we show that FADD-DN also has another cell
      type- and cancer-dependent activity because it induces apoptosis of normal human
      prostate epithelial cells but not normal prostate stromal cells or prostate
      cancer cells. This activity is independent of FADD-DN's ability to bind to three
      known interacting proteins, Fas, TRADD or RIP suggesting that it is distinct from
      FADD's functions at activated death receptors. FADD-DN induces caspase activation
      in normal epithelial cells as demonstrated using a Fluorescence Resonance Energy
      Transfer assay that measures caspase activity in individual living cells.
      However, caspase-independent pathways are also implicated in FADD-DN-induced
      apoptosis because caspase inhibitors were inefficient at preventing prostate cell
      death. Therefore, the death domain of FADD has a previously unrecognized role in
      cell survival that is epithelial-specific and defective in cancer cells. This
      FADD-dependent signaling pathway may be important in prostate carcinogenesis.

PMID- 11464215
TI  - Regulation of cell death and survival in intestinal intraepithelial lymphocytes.
AB  - Intraepithelial lymphocytes (IEL) of the small murine bowel represent a unique
      population of mostly CD8(+) T lymphocytes that reside within the epithelial cell
      layer of the intestinal mucosa. The close interaction with epithelial cells
      appears to be crucial for IEL survival since isolation and ex vivo culture
      induces massive apoptosis in this lymphocyte population. Here, we provide
      evidence that this form of IEL cell death may be mediated at least in part by
      endogenously produced glucocorticoids since adrenalectomy or treatment of mice
      with a glucocorticoid receptor antagonist significantly enhanced ex vivo survival
      of IEL. We further demonstrate that ex vivo activation of IEL induces
      upregulation of anti-apoptotic gene products, compensates for the lack of
      survival cytokines and rescues from apoptotic cell death. Thus, similar to
      thymocytes and T cell hybridomas, IEL survival may be regulated by the
      antagonistic action of TCR activation and glucocorticoids.

PMID- 11464216
TI  - The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human
      leukemia cells (U937) through the mitochondrial rather than the receptor-mediated
      pathway.
AB  - Flavopiridol (FP), an inhibitor of cyclin dependent kinases 1, 2 and 4, potently
      induced apoptosis in U937 human monoblastic leukemia cells. This process was
      accompanied by characteristic morphological changes, inner mitochondrial membrane
      permeability transition, release of cytochrome c, processing of procaspases, and
      generation of reactive oxygen species. Significantly, the general caspase
      inhibitor Boc-FMK did not block the release of cytochrome c, whereas it did block
      cleavage of BID and the loss of Deltapsi(m). Neither FP-induced apoptosis nor
      cytochrome c release was inhibited by the pharmacological caspase-8 inhibitor
      IETD-FMK or endogenous expression of viral caspase-8 inhibitor CrmA. Finally, FP
      mediated apoptosis, but not cytochrome c release, was partially blocked by the
      free radical scavenger LNAC. Collectively, these findings indicate that FP
      induces apoptosis in U937 cells via the release of cytochrome c from the
      mitochondria and independently of activation of procaspase-8.

PMID- 11464217
TI  - The BH3 domain of BAD fused to the Antennapedia peptide induces apoptosis via its
      alpha helical structure and independent of Bcl-2.
AB  - Since the over-expression of Bcl-2 is a common cause of multi-drug resistance,
      cytotoxic peptides that overcome the effects of Bcl-2 may be clinically useful.
      We harnessed the death-promoting alpha helical properties of the BH3 domain of
      BAD by fusing it to the Antennapedia (ANT) domain, which allows for cell entry
      (ANTBH3BAD). Treatment of 32D cells with the ANTBH3BAD peptide results in a 99%
      inhibition of colony formation. No significant toxicity is observed after
      treatment with ANT or BH3BAD alone. A mutant fusion peptide unable to bind Bcl-2
      induces cell death as effectively as the wild-type ANTBH3BAD. Furthermore, 32D
      cells over-expressing Bcl-2 show no resistance to the ANTBH3BAD peptide.
      Therefore, the toxicity of the peptide was independent of the Bcl-2 pathway. We
      demonstrate that the toxicity of the peptide is due to its alpha helicity that
      disrupts mitochondrial function. Since this peptide overcomes major forms of drug
      resistance, it may be therapeutically useful if appropriately targeted to
      malignant cells.

PMID- 11464218
TI  - The trigger to cell death determines the efficiency with which dying cells are
      cleared by neighbours.
AB  - Phagocytosis of apoptotic cells is required to prevent tissue injury.
      Professional phagocytes, such as monocyte-derived macrophages, are highly
      efficient scavengers of apoptotic cells but their presence cannot always be
      relied on; in that case, removal of effete cells is accomplished by helpful
      neighbours. This study describes differences in the efficiency with which
      apoptotic cells of the same type, but dying in response to different triggers,
      are engulfed; this varies from engulfment that is so proficient few or no
      unengulfed apoptotic cells are found, to engulfment that is so delayed apoptotic
      cells have become secondarily necrotic at the point of engulfment. In all cases
      the efficiency of engulfment is determined at least in part by the dying cells
      themselves. p53- and Bax-transfected kidney epithelial (293) cells (transiently
      transfected using a non-toxic method) were engulfed so proficiently by homotypic
      neighbours that cells did not show evidence of engagement of the apoptotic
      programme (chromatin condensation and TUNEL positivity) until engulfment had
      taken place. Engulfment nonetheless required activation of at least initiator
      caspases. 293 cells induced to apoptose by other means (etoposide and
      staurosporine treatment) were not so efficiently ingested: unengulfed apoptotic
      cells were consistently revealed at all doses and time points, even when treated
      cells were mixed with healthy, non-treated 293 cells. These data make it
      extremely unlikely that the fraction of viable, unaffected neighbours determines
      the efficiency with which engulfment proceeds. Furthermore, 293 cells treated
      with etoposide or staurosporine were differentially appealing both to homotypic
      neighbours and to cells in the professional phagocyte lineage (THP-1 cells). If
      different apoptotic stimuli programme cells to be recognised with different
      efficiencies, pathways to apoptosis may be injury limiting to greater or lesser
      degrees.

PMID- 11464219
TI  - Transient protection by peripheral benzodiazepine receptors during the early
      events of ultraviolet light-induced apoptosis.
AB  - The peripheral benzodiazepine receptor (PBR) is a mitochondrial protein involved
      in the formation of mitochondrial permeability transition (PT) pores which play a
      critical role during the early events of apoptosis. PBRs are located in many
      tissues and are strongly expressed in the superficial layers of human epidermis.
      PBRs play a protective role against free radical damage and PBR ligands modulate
      apoptosis. To investigate the role of PBR during the early events of ultraviolet
      (UV)-mediated apoptosis we compared the effects of UVB on PBR-transfected Jurkat
      cells and their wild type counterparts devoid of any PBR expression. Results
      indicate that early after UVB exposure (up to 4 h), PBR-transfected cells were
      more resistant to apoptosis and exhibited a delayed mitochondrial transmembrane
      potential drop, a diminished superoxide anions production, and a reduced caspase
      3 activation. Taken together these findings suggest that PBR may regulate early
      death signals leading to UV induced apoptosis.

PMID- 11464220
TI  - Establishment of okadaic acid resistant cell clones using a cDNA expression
      library.
AB  - The mechanism whereby the universal apoptogen and serine/threonine phosphatase
      inhibitor okadaic acid (OA) kills cells, is still unclear. To create a novel tool
      for probing of OA action, fibroblasts were selected for OA-resistance after
      infection with a retroviral Jurkat T-cell cDNA expression library. Twenty-one
      clones were selected. Two of these (OAR1, OAR2) were studied in detail. OAR1 and
      2 had each a retrovirally introduced short cDNA, corresponding to a human gene
      (oar1 and oar2, respectively) with unknown function. Reintroduction of oar1 or
      oar2 cDNA into wild-type cells reproduced the OA-resistant phenotype. OAR1 and 2
      were cross-resistant to other phosphatase inhibitors (calyculin A, cantharidin),
      but not to staurosporine or microinjected Cytochrome c, thus, indicating a
      disturbance in a limited number of death pathways, upstream or independent of
      apaf-1/caspases-3/9. The action of OA involved caspase-dependent and caspase
      independent components. Both components were less efficient in OAR1 and 2, than
      in wild-type cells. Subtle differences existed between OA-induced phosphoprotein
      patterns in wild-type cells, OAR1, and OAR2, indicating that a narrow selection
      of protein phosphorylation events had been targeted. We propose that the clones
      have defects in a hitherto non-elucidated signal pathway linking OA-induced
      protein phosphorylation to initiation of a death execution pathway provided with
      a caspase-dependent amplification loop. The novel OA-resistant cell clones will
      be used to elucidate the significance for apoptosis of oar1 and 2, their link to
      altered protein phosphorylation, and the potential link of the latter to
      initiation of apoptosis.

PMID- 11464221
TI  - Presence of anti-"tissue" transglutaminase antibodies in inflammatory intestinal
      diseases: an apoptosis-associated event?

PMID- 11464222
TI  - Fas-ligand and immune privilege: the eyes have it.

PMID- 11464223
TI  - Solubilization of phytosterols in diacylglycerol versus triacylglycerol improves
      the serum cholesterol-lowering effect.
AB  - OBJECTIVE: This study was performed to investigate the difference in the serum
      cholesterol- and triglyceride-lowering activities between phytosterols dissolved
      in diacylglycerol (PS/DG) and dispersed in triacylglycerol (PS/TG). The effects
      of the solvent on the concentrations of serum beta-sitosterol and campesterol
      were examined. DESIGN: The study had a randomised crossover design. SUBJECTS:
      Twelve healthy normocholesterolemic or moderately hypercholesterolemic men aged
      29-50 y participated in this study. INTERVENTIONS: For 2 weeks before the test
      period (designated as the control period), all subjects consumed control
      mayonnaise (PS free) daily with supper and were randomly assigned to two groups
      for the 2 week test period; one group was given mayonnaise containing PS (500
      mg/day) dissolved in DG (10 g/day), and the other mayonnaise containing PS (500
      mg/day) dispersed in TG (10 g/day). After a wash out period consuming control PS
      free mayonnaise for 4 weeks, the groups were reversed for 2 weeks. RESULTS: PS/TG
      feeding had no effect on the serum cholesterol level. In contrast, PS/DG feeding
      significantly reduced the total and LDL cholesterol levels from the initial value
      of 5.57 to 5.31 mmol/l (4.7%; P<0.05) and from 3.69 to 3.39 mmol/l (7.6%;
      P<0.05), respectively. Moreover, the degree of total cholesterol reduction
      induced by PS/DG feeding in the test period was significantly greater than that
      induced by PS/TG feeding (P<0.05). In addition, the serum beta-sitosterol and
      campesterol concentrations did not change during the PS/TG or PS/DG feeding
      periods. CONCLUSIONS: Dissolution of PS in DG had a better serum cholesterol
      lowering effect than dissolution in TG. SPONSORSHIP: Kao Corporation.

PMID- 11464224
TI  - Fatty acid status of women of reproductive age.
AB  - OBJECTIVE: Healthy foetal and infant development is dependent on an adequate
      maternal supply of essential and polyunsaturated fatty acids (PUFA). While there
      are published data on the fatty acid status of pregnant women, there are few on
      the status of non-pregnant women of reproductive age. The aims of this study were
      to test the hypotheses that the fatty acid status of non-pregnant women is
      affected by socio-economic status and anthropometric, behavioural and obstetric
      factors. DESIGN: Observational study METHODS: One-hundred and thirty-five women
      of child-bearing age (mean 29.8 y, s.d. 6.92) were invited to provide a blood
      sample and to answer a questionnaire, of whom 114 were included in the study.
      Plasma and red cell total fatty acids were measured as their methyl esters by gas
      chromatography mass spectrometry. RESULTS: On multivariate analyses, use of
      hormonal contraception was independently associated with lower plasma
      polyunsaturated fatty acids (difference between means -2.76, 95% confidence
      interval (-4.64, -0.88), P=0.0034), whereas cigarette smoking was associated with
      higher red cell oleic acid (0.74 (0.18, 1.29), P=0.0094). Fish intake was
      associated with higher red cell total n-3 fatty acids (0.62 (0.27, 0.85),
      P=0.0014). CONCLUSIONS: We have reported data on the range of the fatty acids of
      plasma and red blood cells (RBC) total lipids of 114 healthy women of
      reproductive age. These data provide further information on how socio-economic,
      anthropometric, behavioural and obstetric factors may be relevant to female and
      nutrition and health. SPONSORSHIP: University of Glasgow.

PMID- 11464225
TI  - No effect of copper supplementation on biochemical markers of bone metabolism in
      healthy young adult females despite apparently improved copper status.
AB  - OBJECTIVE: To investigate the effects of increasing Cu intakes, above the usual
      dietary intake, on biomarkers of bone metabolism in healthy young adult females
      (aged 21-28 y) over a 4 week period. DESIGN: A double-blind, placebo-controlled
      randomised repeat crossover Cu supplementation trial. SETTING: The study was
      conducted at the Royal Veterinary and Agricultural University (RVAU), Copenhagen,
      Denmark. SUBJECTS: Sixteen healthy young adult females aged 20-28 y were
      recruited from among students at the RVAU. INTERVENTION: During the 4 week
      intervention periods in this randomised, crossover trial (3x4 weeks with a
      minimum 3 week wash-out period), each subject received, in addition to their
      usual diet, either 3 or 6 mg elemental Cu/day as CuSO4 or a matching placebo. On
      the last 3 days of each dietary period 24 h urines were collected. In addition,
      blood was collected on the last day of each dietary period. RESULTS: Serum Cu and
      erythrocyte superoxide dismutase (but not caeruloplasmin protein concentration or
      activity (putative indices of Cu status)) were significantly increased (P<0.05)
      after daily Cu supplementation with 3 and 6 mg/day for 4 weeks. Serum osteocalcin
      (biomarker of bone formation), urinary creatinine (Cr) concentration, urinary
      pyridinoline (Pyr)/Cr or deoxypyridinoline (Dpyr)/Cr excretion, or daily urinary
      Pyr or Dpyr excretion (biomarkers of bone resorption) were unaffected by Cu
      supplementation. CONCLUSION: Copper supplementation of the usual diet in healthy
      young adult females, while apparently improving Cu status, had no effect on
      biochemical markers of bone formation or bone resorption over 4 week periods.
      SPONSORSHIP: Funding from the European Commission.

PMID- 11464226
TI  - Dietetics in ancient Greek philosophy: Plato's concepts of healthy diet.
AB  - Plato (5th-4th century BC), one of the most important philosophers of Greek
      antiquity, left a valuable spiritual heritage, compiled in his famous dialogues.
      His teachings extend to almost every single field of human knowledge. Among other
      philosophical concepts, Plato's works are imbued with the fundamental principle
      of moderation. This spirit is characteristically evident in his references to
      human diet. According to the philosopher, a moderate and thus a healthy diet,
      consists of cereals, legumes, fruits, milk, honey and fish. However, meat,
      confectionery and wine should be consumed only in moderate quantities. Excesses
      in food lead to ailments and therefore should be avoided. Plato considers
      physicians responsible for the regulation of human diet, for medicine is a
      science and not merely an art as in the case of cookery. The dietary pattern
      presented in Platonic dialogues shares many common components with the highly
      reputed Mediterranean diet. As a whole, Plato's writings represent a valuable
      source for the study of the nutritional customs during the classical period of
      ancient Greece.

PMID- 11464227
TI  - Postnatal iron status of Hong Kong Chinese women in a longitudinal study of
      maternal nutrition.
AB  - OBJECTIVE: To report postnatal iron nutritional status of Hong Kong Chinese women
      during the first 6 months postpartum. DESIGN AND SUBJECTS: A longitudinal study
      examining postnatal calcium and iron status of Hong Kong Chinese breastfeeding
      and formula-feeding women was conducted during 1998. Postpartum women aged 20-40
      y, with no bone or blood disorders were recruited and interviewed at 0
      (baseline), 2, 6 weeks, 3 and 6 months postpartum. Dietary intake was assessed by
      a 3 day dietary record and cross checked by a 24 h recall. Complete blood count
      and serum ferritin level were measured to assess anaemia and iron status. In this
      report, subjects were divided into an anaemic group (haemoglobin level < 10 g/dl)
      and a non-anaemic group (haemoglobin level > or = 10 g/dl) according to baseline
      haemoglobin levels. RESULTS: At baseline, 13/47 (27.7%) subjects were anaemic.
      Two of these 13 anaemic subjects were still anaemic at 3 and 6 months postpartum.
      Anaemic subjects showed significantly (P < 0.01) greater amounts of blood loss
      and a higher rate of primary postpartum haemorrhage than the non-anaemic
      subjects. Daily food intake and dietary nutrient intake did not differ
      significantly between the two groups. During the first 6 weeks postpartum,
      subjects in both groups consumed more poultry and egg, and comparable amounts of
      meat, compared with women in the Hong Kong general population. Iron and vitamin C
      intakes for the majority of subjects reached 60% of the US Recommended Daily
      Allowances. Regression analysis suggested that the rate of change in haemoglobin
      level in the first 6 weeks postpartum was positively correlated with baseline MCV
      level and serum ferritin level, but negatively correlated with baseline
      haemoglobin level. CONCLUSIONS: Blood loss at delivery is an important factor for
      postpartum anaemia. Postnatal recovery of iron status of this group of women
      appeared to be more related to physiological factors than to dietary factors. The
      role of diet as well as other physiological changes in postpartum women requires
      further investigation. Finding ways to minimise blood loss at delivery could be
      the most practical strategy to reduce the rate of postpartum anaemia.
      SPONSORSHIP: CSM was supported by a research studentship from the Research Grants
      Council, Hong Kong.

PMID- 11464228
TI  - A one-year follow-up study in anorexia nervosa. Dietary pattern and
      anthropometrical evolution.
AB  - OBJECTIVE: To find out the modifications and the interrelationships between the
      energy and macronutrient intakes and anthropometric measurements of a group of
      anorexia nervosa patients (ANP), with homogenous diagnosis, age and treatment,
      during a 1 y follow-up. DESIGN: Longitudinal study design. SUBJECTS: Fourteen
      restricting-type ANP in the adolescent age (11-21 y) were recruited for the study
      and evaluated at four time intervals during 1 y of multidisciplinary treatment:
      (a) on admission (AN0); (b) after 1 month (AN1); (c) after 6 months (AN6); (d)
      after 1 y (AN12). MEASURES: Energy and macronutrient composition of the diet (48
      h recall) and anthropometric measurements including skinfold thickness. RESULTS:
      Mean weight and BMI were under the 3rd percentile in AN0. All anthropometrical
      parameters increased significantly in AN1 compared to AN0 and did not change in
      AN6 and AN12. Energy and macronutrient intakes increased significantly in AN1.
      The dietary changes were not maintained in the subsequent time intervals and
      there was an overall tendency to turn back to AN0 results. Energy intake adequacy
      to Spanish Recommended Intakes (RI) showed only an acceptable ratio in AN1 (94%
      RI); however, a preserved protein intake was found throughout the study (mean
      intakes between 128.5% and 230.0% RI). Negative correlations were found at AN12
      between size of arm's subcutaneous fat stores and energy and macronutrient
      intakes. CONCLUSION: In this 1 y follow-up study the decrease in the intake of
      energy and macronutrients after discharge seems to be related to anthropometric
      evolution, so that a return to restrictive eating behaviour had occurred in those
      subjects who had reached the highest values in their subcutaneous fat stores,
      probably related to dissatisfaction with self-body image.

PMID- 11464229
TI  - Comparison of a vitamin E-rich diet and supplemental vitamin E on measures of
      vitamin E status and lipoprotein profile.
AB  - OBJECTIVE: To determine whether dietary modification rather than use of
      supplements can raise indices of vitamin E status to potentially cardioprotective
      levels. DESIGN: Eight week randomised controlled trial with parallel treatments
      to compare increased use of vitamin E-rich foods, supplementation with 200 IU of
      vitamin E, and a placebo. SETTING: Dunedin, New Zealand. SUBJECTS: Ninety
      subjects were recruited, of whom 82 non-smoking, free-living individuals aged 22
      72 y with plasma cholesterol <7.5 mmol/l completed the trial. MAIN OUTCOME
      MEASURES: Dietary intakes, plasma alpha tocopherol, plasma alpha
      tocopherol/cholesterol ratio and lipoprotein cholesterol. RESULTS: Consumption of
      an additional 12 mg of vitamin E (alpha tocopherol equivalents) from dietary
      sources was primarily achieved through the replacement of saturated fat-rich
      foods with unsaturated fats rich in vitamin E, nuts and vegetables. This resulted
      in a 3.4 micromol/l increase in plasma alpha tocopherol at week 6 (95% CI 1.6
      5.3), and 0.9 micromol/mmol in plasma alpha tocopherol/cholesterol at weeks 4 and
      6 (95% CI 0.3-1.4 and 0.4-1.4, respectively) when compared with the placebo
      group. In the supplement group, plasma alpha tocopherol and plasma alpha
      tocopherol/cholesterol were significantly increased within 2 weeks and remained
      so throughout the 8 week intervention. CONCLUSION: Increasing dietary vitamin E
      intake can increase plasma alpha tocopherol levels, although factors other than
      dietary intake are also important determinants. The extent of dietary
      modification required to achieve potentially cardioprotective levels of plasma
      alpha tocopherol is difficult in practice. SPONSORSHIP: The study was supported
      through the Otago Medical Research Foundation Laurenson Award.

PMID- 11464230
TI  - The role of street foods in the dietary pattern of two low-income groups in
      Nairobi.
AB  - OBJECTIVES: To examine the frequency of street food consumption of people living
      in low-income settlements in Nairobi and the role of street foods in their daily
      diet and to reveal why people consume street foods rather than home-prepared
      foods. SETTING, SUBJECTS AND METHODS: A cross-sectional descriptive study was
      done with 1011 households and in-depth interviews with a subsample of 73
      households in two selected areas in Nairobi: Korogocho, a low-income slum area
      and Dandora, a low-middle-income area. RESULTS: The frequency of street food
      consumption was higher in Korogocho than in Dandora (3.6 vs 2.0 days per week;
      P<0.001). Street food consumption did not differ between different types of
      households, with the exception of household size. Employment status of the
      household head and street food consumption were related (P<0.001): consumption
      frequency of 3.7 days per week when irregularly or unemployed, 2.9 days/week when
      self-employed and 2.1 days/week when regularly employed. Furthermore, where an
      adult woman with primarily a domestic role was present, street food consumption
      was less (2.55 days per week when present vs 2.95 when not present; P<0.05).
      CONCLUSIONS: Street foods play an important role in the diet of poor households
      in Nairobi, in particular for breakfast and snacks, because they are cheap and
      convenient. The frequency of street food consumption is determined by a
      combination of at least four factors: level of household income; regularity of
      income; household size; and time available to prepare meals. SPONSORSHIP: The
      project is financed by the Netherlands Foundation for the Advancement of Tropical
      Research (WOTRO), filenumber WV 96-153.

PMID- 11464231
TI  - Food consumption patterns in Italy: the INN-CA Study 1994-1996.
AB  - OBJECTIVES: The present study was aimed at surveying the Italian food consumption
      patterns in the 90s. It represented the second nationwide food intake survey that
      was carried out by the Istituto Nazionale di Ricerca per gli Alimenti e la
      Nutrizione (INRAN). DESIGN: Cross-sectional study. SETTING: Free-living
      households. SUBJECTS: Sampled subjects: 1147 households randomly selected to be
      representative of the four main geographical areas (North-West, North-East,
      Centre, South). Analysed subjects: 1978 individuals out of 2734 initially
      collected in 15 Collaborative Centres strategically scattered through the
      national territory. METHODS: A mixed 7-day based survey technique was applied in
      order to survey both individual and household consumption. At individual level,
      food intake was recorded by a self-compiled diary. At household level food data
      collection was by compilation of a food inventory by the dietician, a
      purchased/wasted foods diary and a recipes form both compiled by the person
      responsible for food related activities (decision of purchase, purchase,
      preparation of meals) in the household. All recorded data were monitored by the
      dieticians who visited the households participating in the study, at least three
      times. Household members were interviewed in order to collect socio-demographic,
      lifestyle and motivational information. Furthermore, field-workers performed the
      food coding and the input of data by an ad hoc developed software. The survey
      design allowed an internal quantitative check of food data. Several check steps
      were centrally performed RESULTS: The complex methodology caused the 46.8%
      response rate and afterwards a reduction of the analysed units (72% of the
      surveyed individuals). However, the analysed sample provided sufficiently
      reliable data for outlining the most relevant aspects of dietary patterns in
      Italy. In order to better interpret the results, controversial aspects are also
      illustrated and discussed in the text. The disparity analysis found that
      traditional diversities among Italian regions are still alive. In general, males
      eat more than females. Analysis according to the age class (children: 1-9 years
      old; adolescents: 10-17; adults: 18-64; elderly: >64) showed differences
      especially between the group of children vs all the others, but also in the two
      groups of young individuals vs adults and the elderly, that could represent clues
      of an incorrect way of eating. CONCLUSIONS: Taking into account the different
      methodology, the comparison with previous results showed changes in the Italian
      average diet complying with an increasing attention to healthy aspects by large
      sectors of the population, but also opposite tendencies that should be carefully
      monitored. SPONSORSHIP: Minister delle Politiche Agricole e Forestali
      (Mi.P.A.F.).

PMID- 11464232
TI  - Oral antioxidant therapy for marginal dry eye.
AB  - OBJECTIVE: To assess the efficacy of an orally administered antioxidant dietary
      supplement for managing marginal dry eye. DESIGN: A prospective, randomised,
      placebo controlled trial with cross-over. SETTING: Eye Clinic, Department of
      Vision Sciences, Glasgow Caledonian University. SUBJECTS: Forty marginal dry eye
      sufferers composed of 30 females and 10 males (median age 53 y; range 38-69 y).
      INTERVENTIONS: Baseline assessments were made of tear volume sufficiency (thread
      test), tear quality (stability), ocular surface status (conjunctival impression
      cytology) and dry eye symptoms (questionnaire). Each subject was administered
      courses of active treatment, placebo and no treatment, in random order for 1
      month each and results compared to baseline. RESULTS: Tear stability and ocular
      surface status were significantly improved following active treatment (P<0.05).
      No changes from baseline were detected following administration of placebo and no
      treatment (P>0.05). Absolute increase in tear stability correlated with absolute
      change in goblet cell population density. Tear volume was not improved following
      any treatment period and dry eye symptom responses were subject to placebo
      effect. CONCLUSIONS: Oral antioxidants improved both tear stability and
      conjunctival health, although it is not yet understood whether increased ocular
      surface health mediates increased tear stability or vice versa. SPONSORS: This
      study was supported by a PhD scholarship funded by the Department of Vision
      Sciences, Glasgow Caledonian University, Scotland. Antioxidant supplements and
      placebos were kindly donated by Vitabiotics.

PMID- 11464233
TI  - Iron status of premenopausal women in two regions of Bangladesh: prevalence of
      deficiency in high and low socio-economic groups.
AB  - OBJECTIVE: The objective of the study was to assess iron status in women of
      different physiological status of two socio-economic groups in Bangladesh.
      DESIGN: Cross sectional study, using 3-day food record and blood haemoglobin,
      serum iron, serum ferritin concentrations. SETTING: Two regions of Bangladesh.
      The Dhaka city area and west region of Nandail, Mymensingh. SUBJECTS: Women aged
      16-40 y. The low socio-economic group (group L, n=101) consisted of rural women
      with precarious income levels. The high socio-economic group (group H, n=90)
      consisted of women with high income and educational levels. The groups were
      composed of three sub-groups (non-pregnant non-lactating=1, pregnant = 2 and
      lactating = 3). RESULTS: There was no significant difference between the
      corresponding sub-groups of the two socio-economic groups in dietary intake of
      iron. In all sub-groups, the intake of iron was much higher than the RDA level
      and mainly based on non-haem iron. Blood haemoglobin (B-Hb) concentration
      (P=0.000), serum iron concentration (P=0.005) and serum ferritin (SF)
      concentration (P=0.000) were affected by socio-economic status. Physiological
      status (PS) influenced the B-Hb concentration (P=0.000). Prevalence of anaemia
      ranged from 63 to 70% in group L and 27 to 66% in group H, respectively. The
      prevalence of empty iron store (SF concentration<12 microg/l) ranged from 35 to
      59% in group L and 15 to 32% in group H, respectively. The prevalence of anaemia
      and iron deficiency (70 and 35% for sub-group L2; 66 and 32% for sub-group H2,
      respectively) were similar in the pregnant subjects of the two groups.
      CONCLUSIONS: Subclinical iron deficiency was common in women of low socio
      economic status. The pregnant subjects in the two groups was similar as regards
      iron status. SPONSORSHIP: The study was supported by the Academy of Finland,
      University of Helsinki and NorFa, Norway.

PMID- 11464234
TI  - A population study of the influence of beer consumption on folate and
      homocysteine concentrations.
AB  - OBJECTIVE: Mild hyperhomocysteinemia is a significant and independent risk factor
      for vascular diseases. Blood total homocysteine concentration (tHcy) is
      considered to be the product of an interaction between genetic and nutritional
      factors notably intake of folate, vitamin B12 and pyridoxine. The aim of the
      study was to determine whether regular intake of beer containing large amount of
      folate and other vitamins influences the tHcy blood concentrations. DESIGN: Cross
      sectional population-based survey. SETTING: Adult population, residents of Pilsen
      (Czech Republic) and vicinity. SUBJECTS: Population series included 292 males and
      251 females aged 35-65 y, mean age 53.4 y. All subjects were examined by a
      standard protocol for clinical, anthropometrical and laboratory estimations. MAIN
      OUTCOME MEASURES: tHcy was measured by high-pressure liquid chromatography with
      fluorescent detection, blood folate and B12 levels immunochemically using
      commercial kits. RESULTS: Beer intake was associated with blood folate and
      vitamin B12 concentrations positively and with tHcy concentration negatively. By
      categories of beer intake, subjects with intake of 1 l daily or more had
      significantly lower tHcy and higher folate concentrations than those reporting
      lower daily beer intake. CONCLUSION: Moderate beer consumption may help to
      maintain the tHcy levels in the normal range due to high folate content. Folate
      from beer may thus contribute to the protective effect of alcohol consumption on
      cardiovascular disease in population with generally low folate intake from other
      nutrients. SPONSORSHIP: Supported by grant 301/00/P089 Grant Agency of Czech
      Republic and Internal Grant Agency of the Ministry of Health.

PMID- 11464235
TI  - Percutaneous endoscopic gastrostomy: a prospective analysis of hospital support
      required and complications following discharge to the community.
AB  - INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is the commonest method
      of long-term enteral nutrition. In the UK there is no nationally funded framework
      to provide community support for patients with gastrostomies. OBJECTIVES: To
      assess the hospital support required and the complications occurring in a cohort
      of patients discharged into the community with a gastrostomy in-situ. DESIGN AND
      SETTING: We prospectively collected data between June and November 1998 regarding
      patients (n=87) with PEG complications in the community following discharge from
      two adjacent hospitals in South Yorkshire (Rotherham District General Hospital
      and the Royal Hallamshire Hospital). RESULTS: The mortality within this cohort
      during the study period was 17.2%. Of these 15 patients 10.3% (n=9) were thought
      to have died as a result of the progression of their disease, whilst in the other
      6.9% (n=6) pneumonia was documented as the cause of death. Problems with
      gastrostomies requiring telephone advice occurred in 24.1% of patients and 65.5%
      necessitated a home visit. However during this period of 6 months, 23% of
      patients were admitted as an emergency, accounting for 61 in-patient days. All
      were from nursing or residential homes and the emergency occurred after normal
      surgery hours. General practitioners dealt with aspiration pneumonia in 25.2% of
      the cohort but other tube problems were referred to the endoscopy unit.
      DISCUSSION: This is the first study to specifically highlight the specialist
      intervention and support required by patients discharged into the community with
      PEGs, a group for whom there is often no formal aftercare. A specialist nurse or
      dietician could establish a liaison service focusing on primary care and using
      hospital resources when appropriate. This study provides further evidence to
      support the recommendations for tube feeding made by the British Association for
      Parenteral and Enteral Nutrition.

PMID- 11464236
TI  - Determinants of glycated haemoglobin in the general population: associations with
      diet, alcohol and cigarette smoking.
AB  - OBJECTIVE: We evaluated cigarette smoking, alcohol intake and consumption of
      different foods as determinants of glycated haemoglobin in a general population
      sample. DESIGN: Cross-sectional survey. SETTING: England. SUBJECTS:
      Representative sample of 15 809 adults aged 16 y and older. Data analysed for
      9772 non-diabetic, white European subjects. MAIN OUTCOME MEASURES: Glycated
      haemoglobin (GHb). Analyses were adjusted for age, sex, body mass index (BMI),
      waist-hip circumference ratio, activity level, and educational attainment.
      RESULTS: After adjusting for confounding, GHb was 0.277% (95% confidence interval
      0.218 to 0.336) higher in current smokers of 20 or more per day, compared with
      non-smokers. GHb was 0.189% (0.101 to 0.277) lower in those drinking 42 or more
      units of alcohol per week than in non-drinkers. GHb was not associated with
      frequency of consumption of pulses, fruit, vegetables and salads, cakes, bread or
      confectionery. GHb was higher in subjects who took sugar in tea (0.051%, 0.015 to
      0.087%) or in coffee (0.069%, 0.034 to 0.105%). GHb was higher in subjects who
      used solid fat for cooking (0.082%, 0.022 to 0.142%), or who drank whole rather
      than reduced-fat milk (0.088%, 0.036 to 0.140%), or used butter or hard margarine
      rather than low-fat spreads (0.075%, 0.029 to 0.121%). CONCLUSIONS: In the
      general population, higher GHb may be associated with cigarette smoking, or
      frequent consumption of fat-containing foods. Consumption of alcohol may be
      associated with lower GHb. SPONSORSHIP: None.

PMID- 11464238
TI  - The spectrum of Familial Mediterranean Fever (FMF) mutations.
AB  - Familial Mediterranean Fever (FMF) is the prototype of a group of inherited
      inflammatory disorders. The gene (MEFV) responsible for this disease, comprises
      10 exons and 781 codons. Twenty-nine mutations, most located in the last exon,
      have been identified so far. It is unclear whether all are true disease-causing
      mutations. Five founder mutations, V726A, M694V, M694I, M680I and E148Q account
      for 74% of FMF chromosomes from typical cases (Armenians, Arabs, Jews, and
      Turks). Rare mutations are preferentially found in populations not usually
      affected by FMF (eg Europeans not from the above ancestries). The various
      combinations of MEFV mutations define severe to mild genotypes. The trend is that
      genotypes including two mutations located within mutational 'hot-spots' (codons
      680 or 694) of the gene are associated with severe phenotypes, whereas mild
      phenotypes are associated with some other mutations, E148Q being the mildest and
      least penetrant. Understanding the correlation between the FMF phenotype and
      genotype is further obscured by the existence of complex alleles, modifier loci,
      genetic heterogeneity and possible epigenetic factors. Additionally, mutations in
      the MEFV gene are thought to be involved in non FMF disorders. Carrier rates for
      FMF mutations may be as high as 1:3 in some populations, suggesting that the
      disease is underdiagnosed. This review update emphasises that both clinical and
      genetic features are to be taken into account for patient diagnosis, colchicine
      treatment and prognosis.

PMID- 11464239
TI  - Best practice guidelines for molecular analysis in spinal muscular atrophy.
AB  - With a prevalence of approximately 1/10 000, and a carrier frequency of 1/40-1/60
      the proximal spinal muscular atrophies (SMAs) are among the most frequent
      autosomal recessive hereditary disorders. Patients can be classified clinically
      into four groups: acute, intermediate, mild, and adult (SMA types I, II, III, and
      IV, respectively). The complexity and instability of the genomic region at
      chromosome 5q13 harbouring the disease-causing survival motor neuron 1 (SMN1)
      gene hamper molecular diagnosis in SMA. In addition, affected individuals with
      SMA-like phenotypes not caused by SMN1, and asymptomatic individuals with two
      mutant alleles exist. The SMN gene is present in at least one telomeric (SMN1)
      and one centromeric copy (SMN2) per chromosome in normal (non-carrier)
      individuals, although chromosomes containing more copies of SMN1 and/or SMN2
      exist. Moreover, the two SMN genes (SMN1 and SMN2) are highly homologous and
      contain only five base-pair differences within their 3' ends. Also, a relatively
      high de novo frequency is present in SMA. Guidelines for molecular analysis in
      diagnostic applications, carrier detection, and prenatal analysis using direct
      and indirect approaches are described. Overviews of materials used in the
      molecular diagnosis as well as Internet resources are included.

PMID- 11464240
TI  - Men at risk of being a mutation carrier for hereditary breast/ovarian cancer: an
      exploration of attitudes and psychological functioning during genetic testing.
AB  - Males with a BRCA1/BRCA2 mutation are not at greatly increased risk for cancer,
      whereas their (grand)daughters, and other female relatives who carry the
      mutation, are. Males from BRCA1/BRCA2 families may opt for genetic testing to
      confirm whether or not they may have transmitted the mutation to their children
      and, if so, to inform them at an appropriate age about the genetic risk and its
      implications. The psychological implications of genetic testing for men at risk
      of being a BRCA1/BRCA2 mutation carrier have received little attention. We report
      on 28 men requesting BRCA1 or BRCA2 testing, and their partners. Men were at 25%
      (n =4) or 50% risk (n =24) of being a mutation carrier, the majority with
      daughters and half of them with daughters aged over 20 years. Levels of
      psychological distress were assessed several weeks before and after disclosure of
      the test result. In addition, we investigated the level of intrusive thoughts and
      feelings about breast and ovarian cancer and the tendency to avoid these. By
      means of interviews and questionnaires, participants could report on (expected)
      emotional implications of genetic testing for themselves and their children, on
      experiences with cancer in the family and on personality trait optimism. Distress
      levels prior to the result in tested men and their partners were low. Many men
      and partners expected the test result to affect their children's, but not their
      own level of problems. Men without daughters and those with an optimistic
      personality had especially low distress prior to disclosure. Most men reported
      that they did not actively avoid the issue. Only four of the 28 men were
      identified as mutation carriers. High distress after disclosure of the result was
      reported by one mutation carrier and by three non-mutation carriers. Verbatim
      transcripts from interviews showed a large variation of psychological reactions
      in male mutation carriers (eg regarding guilt feelings). Low pre-test distress in
      males does not necessarily indicate avoidance of the issue. Future studies may
      indicate which psychological reactions occur in male mutation carriers when the
      problem becomes more acute, eg when a daughter is found to carry the mutation
      and/or is diagnosed with breast or ovarian cancer.

PMID- 11464241
TI  - Physical and transcriptional map of the hereditary inclusion body myopathy locus
      on chromosome 9p12-p13.
AB  - Hereditary inclusion body myopathy (HIBM) is a group of neuromuscular disorders
      characterised by adult-onset, slowly progressive distal and proximal muscle
      weakness and typical muscle pathology. Previously, we have mapped the gene
      responsible for a recessive form of HIBM to chromosome 9p1 and narrowed the
      interval to one single YAC clone of 1 Mb in size. As a further step towards the
      identification of the HIBM gene, we have constructed a detailed physical and
      transcriptional map of this region. A high resolution BAC contig that includes
      the HIBM critical region, flanked by marker 327GT4 and D9S1859, was constructed.
      This contig allowed the precise localisation of 25 genes and ESTs to the proximal
      region of chromosome 9. The expression pattern of those mapped genes and ESTs was
      established by Northern blot analysis. In the process of refining the HIBM
      interval, 13 new polymorphic markers were identified, of which 11 are CA-repeats,
      and two are single nucleotide polymorphisms. Certainly, this map provides an
      important integration of physical and transcriptional information corresponding
      to chromosome 9p12-p13, which is expected to facilitate the cloning and
      identification not only of the HIBM gene, but also other disease genes which map
      to this region.

PMID- 11464242
TI  - Functional characterization of novel mutations in the human cytochrome b gene.
AB  - The great variability of the human mitochondrial DNA (mtDNA) sequence induces
      many difficulties in the search for its deleterious mutations. We illustrate
      these pitfalls by the analysis of the cytochrome b gene of 21 patients affected
      with a mitochondrial disease. Eighteen different sequence variations were found,
      five of which were new mutations. Extensive analysis of the cytochrome b gene of
      146 controls found 20 supplementary mutations, thus further demonstrating the
      high variability of the cytochrome b sequence. We fully evaluated the functional
      relevance of 36 of these 38 mutations using indirect criteria such as the nature
      of the mutation, its frequency in controls, or the phylogenetic conservation of
      the mutated amino acid. When appropriate, the mtDNA haplotype, the heteroplasmic
      state of the mutation, its tissue distribution or its familial transmission were
      also assessed. The molecular consequences of the mutations, which appeared
      possibly deleterious in that first step of evaluation, were evaluated on the
      complex III enzymological properties and protein composition using specific
      antibodies that we have generated against four of its subunits. Two original
      deleterious mutations were found in the group of seven patients with overt
      complex III defect. Both mutations (G15150A (W135X) and T15197C (S151P)) were
      heteroplasmic and restricted to muscle. They had significant consequences on the
      complex III structure. In contrast, only two homoplasmic missense mutations with
      dubious clinical relevance were found in the patients without overt complex III
      defect.

PMID- 11464243
TI  - Comprehensive methylation analysis in typical and atypical PWS and AS patients
      with normal biparental chromosomes 15.
AB  - Imprinting defects in 15q11-q13 are a rare but significant cause of Prader-Willi
      syndrome (PWS) and Angelman syndrome (AS). Patients with an imprinting defect
      have apparently normal chromosomes 15 of biparental origin, but are recognised by
      @parental DNA methylation at D15S63 (PW71) or SNURF-SNRPN exon 1. We have
      investigated the methylation status of five additional loci in 12 such patients
      with or without a deletion in the imprinting centre. In each patient, the
      imprinting defect affected all loci tested. During routine diagnostic testing we
      identified four patients who had a normal methylation pattern at SNURF-SNRPN exon
      1, but an abnormal pattern at D15S63. In two of these patients, who were
      suspected of having PWS, this change was restricted to D15S63. In two patients
      suspected of having AS, several but not all loci were affected. Using a newly
      developed methylation-specific PCR test for D15S63 we found that these
      methylation changes are rare in patients suspected of having AS. Although we can
      not prove that the methylation changes in the four patients are causally related
      to their disease, our findings demonstrate that spatially restricted changes in
      methylation can occur. In some cases, these changes may reflect incomplete
      imprint spreading.

PMID- 11464244
TI  - Screening for subtelomeric chromosome abnormalities in children with idiopathic
      mental retardation using multiprobe telomeric FISH and the new MAPH telomeric
      assay.
AB  - Subtelomeric chromosomal abnormalities are emerging as an important cause of
      human genetic disorders. The scope of this investigation was to screen a selected
      group of children with idiopathic mental retardation for subtelomeric anomalies
      using the multiprobe telomeric FISH method and also to develop and test a new
      assay, the MAPH telomeric assay, in the same group of patients. The new MAPH
      telomeric assay uses the recently published MAPH methodology that permits the
      measurement of locus copy number by hybridisation with a specifically designed
      set of probes located at the end of human chromosomes. Seventy patients with
      idiopathic mental retardation have been screened using the established multiprobe
      telomeric FISH assay and the new MAPH telomeric assay, for all telomeres. One
      patient with de novo 8p subtelomeric deletion was identified. The new MAPH
      telomeric assay confirmed the same results in both normal and abnormal samples.
      This is the first description of the use of MAPH methodology to detect
      chromosomal imbalances near the telomeres in idiopathic mentally retarded
      patients. The new MAPH telomeric assay offers a new, fast, accurate and cost
      effective diagnostic tool to detect chromosomal imbalances near telomeres in
      mentally retarded patients, as well as the characterisation of known chromosomal
      abnormalities, spontaneous recurrent miscarriages, infertility, hematological
      malignancies, preimplantation genetic diagnosis, and other fields of clinical and
      research interests.

PMID- 11464245
TI  - Linear increase of diploidy in human sperm with age: a four-colour FISH study.
AB  - The aim of this study was to determine if donor age is associated with an
      increased incidence of diploidy and of disomy for the sex chromosomes and for
      chromosomes 6 and 21. We used simultaneous fluorescence in situ hybridisation
      (FISH) for chromosomes 6, 21, X and Y in sperm from 18 healthy donors, aged 24-74
      years (mean 48.8 years). A total of 194 024 sperm were analysed, with a minimum
      of 10 000 sperm scored for each donor. Our results indicate a significant
      increase of the level of diploidy (P=0.002), and a marginal significance of total
      sex chromosome disomy (P=0.055) with age. No increase was observed for disomies
      XX, YY, XY, 21 or 6. The percentages of increase for disomy and for diploidy
      ranged from 0.3 to 17% for each 10-year period. Chromosomes 6 and 21 did not
      segregate preferentially with the X or Y chromosomes. Our findings show a linear
      trend association between age and diploidy in human males.

PMID- 11464246
TI  - Cytogenetic analyses of culture failures by comparative genomic hybridisation
      (CGH)-Re-evaluation of chromosome aberration rates in early spontaneous
      abortions.
AB  - Comparative genomic hybridisation (CGH) represents an alternative molecular
      cytogenetic technique capable of detecting chromosomal imbalances by reverse
      fluorescence in situ hybridisation. As the technique uses genomic DNA for
      assessment it does not rely on metaphase chromosomes in the test material and
      thus circumvents technical problems associated with tissue culturing. In the
      present study, we applied CGH to identify chromosome anomalies in 60 spontaneous
      abortions of the first trimester, that had failed to grow in culture. In 57 out
      of 60 cases CGH analyses were successful. The overall aneuploidy rate detected
      was 72%. Trisomy was the predominant chromosome anomaly accounting for 68.0% of
      abnormal abortions, followed by triploidy (17.1%) and monosomy X (9.8%). An
      unbalanced structural rearrangement was found in one (2.4%) abortion. Most
      frequently involved in trisomies were chromosomes 16 (32.1%), 7 and 22 (10.7%
      each), 4, 13, 15, and 21 (7.2 % each). Three triploid cases and one complete mole
      were detected by microsatellite analysis as supplementary method. CGH data on
      culture failures were compared with data derived from 4693 successfully
      karyotyped first trimester spontaneous abortions, resulting in a chromosome
      aberration rate of 64.8%. The distribution of the different chromosome anomalies
      was similar with the exception of a higher rate of trisomies 7 and of XYY
      triploidies in the culture failures. Based on our data we suggest that the
      genetic contribution to pregnancy loss is still underestimated. Investigating
      abortion tissues hitherto unassessed by conventional methods, we suggest that the
      contribution of chromosome aberrations to first trimester pregnancy loss is
      nearly 70%.

PMID- 11464247
TI  - MUC1 gene polymorphism in the gastric carcinogenesis pathway.
AB  - MUC1 like most mucin genes shows extensive length polymorphism in the central
      core region. In a previous study it was shown that individuals with small MUC1
      alleles/genotypes have an increased risk for development of gastric carcinoma.
      Our aim was to see if MUC1 gene polymorphism was involved in susceptibility for
      the development of conditions that precede gastric carcinoma: chronic atrophic
      gastritis (CAG) and intestinal metaplasia (IM). We evaluated MUC1 polymorphism in
      a population of 174 individuals with chronic gastritis (CG) displaying (CAG)
      and/or intestinal metaplasia (IM). The population of patients with CG shows MUC1
      allele frequencies significantly different from the gastric carcinoma patients
      and blood donors population. A significantly lower frequency of CAG and IM was
      observed in MUC1 VNTR heterozygotic patients. Within the group of patients with
      IM, MUC1 large VNTR homozygotes show a significantly higher frequency of complete
      IM while small VNTR homozygotes show a significantly higher frequency of
      incomplete IM. These findings show that MUC1 polymorphism may define different
      susceptibility backgrounds for the development of conditions that precede gastric
      carcinoma: chronic atrophic gastritis (CAG) and intestinal metaplasia (IM).

PMID- 11464248
TI  - Mutation frequency of Familial Mediterranean Fever and evidence for a high
      carrier rate in the Turkish population.
AB  - Familial Mediterranean Fever (FMF) is a recessive disorder characterised by
      episodes of fever and neutrophil-mediated serozal inflammation. The FMF gene
      (MEFV) was recently identified and four common mutations characterised. The aim
      of this study was to determine the carrier rate in the Turkish population and the
      mutation frequency in the clinically diagnosed FMF patients. We found a high
      frequency of carriers in the healthy Turkish population (20%). The distribution
      of the five most common MEFV mutations among healthy individuals (M694V 3%, M680I
      5%, V726A 2%, M694I 0% and E148Q 12%) was significantly different (P<0.005) from
      that found in patients (M694V 51.55%, M680I 9.22%, V726A 2.88%, M694I 0.44% and
      E148Q 3.55%).

PMID- 11464249
TI  - No mutations in the coding region of the Rett syndrome gene MECP2 in 59 autistic
      patients.
AB  - Autistic disorder is a pervasive developmental disorder considered to have a
      multigenic origin. Mental retardation is present in 75% of autistic patients.
      Autistic features are found in Rett syndrome, a neurological disorder affecting
      girls and associated with severe mental retardation. Recently, the gene
      responsible for the Rett syndrome, methyl CpG-binding protein (MECP2) gene, was
      identified on the X chromosome by a candidate gene strategy. Mutations in this
      gene were also observed in some mentally retarded males. In this study we tested
      MECP2 as a candidate gene in autistic disorder by a DGGE analysis of its coding
      region and intron-exon boundaries. Among 59 autistic patients, 42 males and 17
      females, mentally retarded or not, no mutations or polymorphisms were present in
      the MECP2 gene. Taking into account the size of our sample, we conclude that
      MECP2 coding sequence mutations are not an important factor (less than 5% of
      cases) in the aetiology of autistic disorder.

PMID- 11464251
TI  - Right atrial function in hypertension.

PMID- 11464252
TI  - First-line treatment of hypertension: from monotherapy to fixed low-dose
      combination therapy.

PMID- 11464253
TI  - Peripheral vascular disease and hypertension: a forgotten association?
AB  - Peripheral vascular disease (PVD) is associated with a high cardiovascular
      morbidity and mortality. Intermittent claudication is the most common symptomatic
      manifestation of PVD, but is also an important predictor of cardiovascular death,
      increasing it by three-fold, and increasing all-cause mortality by two to five
      fold. Hypertension is a common and important risk factor for vascular disorders,
      including PVD. Of hypertensives at presentation, about 2-5% have intermittent
      claudication, with this prevalence increasing with age. Similarly, 35-55% of
      patients with PVD at presentation also have hypertension. Patients who suffer
      from hypertension with PVD have a greatly increased risk of myocardial infarction
      and stroke. Apart from the epidemiological associations, hypertension contributes
      to the pathogenesis of atherosclerosis, the basic underlying pathological process
      underlying PVD. Hypertension, in common with PVD, is associated with
      abnormalities of haemostasis and lipids, leading to an increased atherothrombotic
      state. Nevertheless, none of the large antihypertensive treatment trials have
      adequately addressed whether a reduction in blood pressure causes a decrease in
      PVD incidence. There is therefore an obvious need for such outcome studies,
      especially since the two conditions are commonly encountered together.

PMID- 11464254
TI  - Calcium channel blockers, postural vasoconstriction and dependent oedema in
      essential hypertension.
AB  - Treatment with calcium channel blocker (CCB)s, dihydropyridines and others, is
      frequently complicated by dependent oedema in the absence of sodium retention or
      cardiac failure, a bothersome side effect of unclear aetiology. The present paper
      reviews our own and other work dealing with the antagonism exerted by such drugs
      on postural vasoconstriction, a mechanism triggered by limb venous congestion
      during orthostasis and controlled through a local sympathetic axo-axonic reflex
      and increased myogenic tone in response to changes in transmural pressure. By
      stabilising capillary pressure, postural vasoconstriction counteracts fluid
      hyperfiltration consequent to gravitational stimuli, and consistent evidence
      shows attenuation of this response by L-type calcium channel blockers.
      Interference with the postural reflex control of skin blood flow may therefore
      contribute to dependent oedema, although cannot entirely explain its development.
      Attenuation of postural vasoconstriction may amplify the fluid hyperfiltration
      induced by CCBs through other mechanisms, such as imbalanced intracapillary
      pressure or enhanced vascular permeability, which are the main factors
      determining net fluid filtration into the interstitial compartment.

PMID- 11464255
TI  - Right atrial function in hypertensive patients: effects of antihypertensive
      therapy.
AB  - OBJECTIVES: The effects (16 weeks) of oral antihypertensive drugs on right atrial
      (RA) function were evaluated by two-dimensional and Doppler echocardiography in
      64 patients with mild-to-moderate essential hypertension. Thirty-two age- and sex
      matched normal subjects served as controls. BACKGROUND: Hypertension alters the
      diastolic properties of the left ventricle and disturbs the left atrial
      contractile activities. RA performance may also alter in essential hypertension.
      METHODS: From the tricuspid flow velocity curves the E/A ratio, the velocity-time
      integrals (Ei and Ai, respectively) as well as the sum, TTi = Ei + Ai, were
      measured. RA active contribution (RAAC) was expressed as the ratio RAAC = Ai/TTi.
      RESULTS: RA-A/E ratio, RA-Ai and RAAC were increased while RA-TTi were decreased
      in hypertensives compared to controls, P < 0.0001 for all comparisions. After
      therapy TTi increased (from 13.2 +/- 1.6 to 16.2 +/- 2.0 cm with ramipril, and
      from 12.9 +/- 1.1 to 14.4 +/- 1.2 cm with amlodipine, P < 0.001) and RAAC
      decreased (from 0.19 +/- 0.01 to 0.13 +/- 0.01, with ramipril and from 0.19 +/-
      0.01 to 0.16 +/- 0.00, with amlodipine P < 0.001) while RA dimensions did not
      change. the decrease in RAAC was significantly greater with ramipril (P < 0.001)
      and was significantly influenced by the decrease in left ventricular mass (P <
      0.001) and right ventricular relaxation (P < 0.001). CONCLUSIONS: RA function is
      deteriorated in patients with essential hypertension. The fall in the arterial
      blood pressure produced by antihypertensive treatment was associated with
      improved RA performance and reduced left ventricular mass without changes in RA
      dimensions. The left ventricular mass and the right ventricular relaxation
      influenced the changes in RA performance.

PMID- 11464256
TI  - Systematic screening of type B human natriuretic peptide receptor gene
      polymorphisms and association with essential hypertension.
AB  - C-type natriuretic peptide (CNP) dilates arteries, lowers blood pressure and
      inhibits proliferation of vascular smooth muscle cells via the type B natriuretic
      peptide receptor (NPRB). The CNP-NPRB system may play a crucial role in the
      development of cardiovascular disease. We recently determined the structure of
      the human NPRB gene. In the present study, our objectives are to identify the
      polymorphisms of the NPRB gene and investigate the association of this gene with
      essential hypertension (EH). We used the polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) technique to study the NPRB gene
      polymorphism, and conducted an association study using a novel polymorphic
      marker. PCR-SSCP analysis of all 22 exons was done in 90 subjects, and abnormally
      migrating bands were observed in the analyses of exon 11 and intron 18. Direct
      sequencing of these DNA fragments revealed the following sequence alterations: a
      C to T transition at nucleotide (nt) 2077 in exon 11 and a 9-bp
      insertion/deletion (I/D) in intron 18. PCR-restriction fragment length
      polymorphism analysis (PCR-RFLP) was developed to detect the C2077T transition.
      PCR-RFLP analyses of healthy subjects revealed that the C2077T polymorphism had
      complete linkage to GT repeats in intron 2 reported previously. The I/D
      polymorphism was identified by polyacrylamide gel electrophoresis, and it was not
      linked to any known polymorphic alleles of this gene. Therefore, the possible
      association between the I/D polymorphism and EH was investigated. A total of 123
      individuals with EH and 123 age-matched normotensive control subjects were
      studied. Overall distributions of allele frequencies in the two groups were not
      significantly different. Although the I/D polymorphism in intron 18 of the NPRB
      gene was not associated with EH, the results of this study, which identified two
      novel polymorphisms in the human NPRB gene, will facilitate further genetic
      analysis of this gene and cardiovascular disease.

PMID- 11464257
TI  - A forced titration study of antihypertensive efficacy of candesartan cilexetil in
      comparison to losartan: CLAIM Study II.
AB  - An 8-week, multicentre (72 sites in the US), double-blind, randomised, parallel
      group, forced titration study compared the antihypertensive efficacy of
      candesartan cilexetil and losartan. A total of 611 patients with essential
      hypertension (diastolic blood pressure 95 to 114 mm Hg) were randomised initially
      to candesartan cilexetil 16 mg once daily or losartan 50 mg once daily. After 2
      weeks of randomised treatment, the doses of candesartan cilexetil and losartan
      were doubled to 32 mg and 100 mg once daily and continued respectively for 6
      weeks. At week 8, candesartan cilexetil lowered the blood pressure (BP) at 24 h
      (trough), 6 h (peak) and 48 h post dose to a significantly greater extent (P <
      0.05) than losartan: candesartan cilexetil lowered trough BP by 13.4/10.5 mm Hg,
      peak BP by 15.5/12.9 mm Hg and 48-h BP by 10.5/9.9 mm Hg compared to a reduction
      of trough BP by 10.1/9.1 mm Hg, peak BP by 12.0/9.5 mm Hg, and 48-h BP by 5.9/7.0
      mm Hg by losartan. The responder and control rates were numerically higher in the
      candesartan cilexetil group, but the differences did not reach statistical
      significance; the responder rates were 58.8% for the candesartan cilexetil group
      and 52.1% for the losartan group and control rates were 49.0% for the candesartan
      cilexetil group and 44.6% for the losartan group. Overall, both treatment
      regimens were well tolerated. A total of 15 of the 611 (2.5%) patients withdrew
      from the study due to an adverse event, including nine (2.9%) in the candesartan
      cilexetil group and six (2.0%) in the losartan group. In conclusion, this forced
      titration study confirms that candesartan cilexetil is more effective in lowering
      BP than losartan when compared at once daily maximum doses.

PMID- 11464258
TI  - Increased insulin resistance in salt sensitive essential hypertension.
AB  - OBJECTIVE: To determine the possible relationship between insulin resistance and
      salt sensitivity in essential hypertension. DESIGN AND METHODS: We studied 17 non
      obese, essential hypertensive patients (24-h blood pressure: 149 +/- 15/94 +/- 5
      mm Hg) with normal glucose tolerance. Salt sensitivity was diagnosed in the
      presence of a significant increase (P < 0.05, more than 4 mm Hg) in 24-h mean
      blood pressure (MBP) when patients switched from a low-salt intake (50 mmol/day
      of Na(+)) to a high-salt intake (240 mmol/day of Na(+)), each period lasting 7
      days. The insulin sensitivity index was determined by the euglycaemic
      hyperinsulinaemic clamp. RESULTS: Six patients were classified as salt sensitive
      (24-h MBP increase: 6.2 +/- 1.1 mm Hg), and 11 as salt resistant (24-h MBP
      increase: -1.2 +/- 3.8 mm Hg). No significant differences were observed between
      salt sensitive and salt resistant patients regarding baseline characteristics,
      fasting serum insulin, fasting serum glucose, glycosylated haemoglobin, total
      cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, uric acid and
      microalbuminuria. Salt sensitive patients exhibited a reduced insulin sensitivity
      index compared with salt resistant patients (1.7 +/- 1.1 vs 3.5 +/- 1.2
      mg/kg/min; P = 0.009). An inverse relationship (r -0.57; P = 0.016) between the
      insulin sensitivity index and 24-h MBP increase with high salt intake was found.
      CONCLUSION: Salt sensitive essential hypertensive patients are more insulin
      resistant than salt resistant patients when both salt sensitivity and insulin
      resistance are accurately measured. Indirect measures of both insulin and salt
      sensitivity and/or the presence of modifying factors, such as obesity or glucose
      intolerance, may account for differences in previous studies.

PMID- 11464259
TI  - A comparison of dietary and non-dietary factors of hypertension and normal blood
      pressure in a Chinese population.
AB  - The aim of this study was to compare the differences of dietary and non-dietary
      factors in hypertension and normal blood pressure (BP) of Chinese urban people.
      Two cross-sectional population surveys were carried out in Tianjin, one of the
      three largest cities in China. A total of 2068 subjects aged 35-64 years were
      selected by a random stratified cluster sampling, 367 men and 395 women were
      hypertensive, and 623 men and 683 women had normal BP. The diet was assessed by
      food weighing plus consecutive individual 3-day food records. Health status,
      health behaviours and anthropomentry were assessed. The whole population had a
      high sodium and low potassium consumption level. Hypertensive men and women had
      significantly higher daily dietary sodium intake (P < 0.05) and hypertensive
      women had higher dietary sodium-to-potassium ratio (P < 0.01) than men and women
      with normal BP. Age, body mass index, overweight and family history of
      hypertension were positively related to high BP. dietary sodium intake and
      dietary sodium-to-potassium ratio were positively associated with high BP.
      Education level in women and commuting physical activity in men were inversely
      associated with high BP.

PMID- 11464260
TI  - Once-daily treatment of patients with hypertension: a placebo-controlled study of
      amlodipine and benazepril vs amlodipine or benazepril alone.
AB  - OBJECTIVE: To compare the efficacy, tolerability, and safety of once-daily
      therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg, benazepril 10
      mg, and placebo. DESIGN: Randomised, double-blind, placebo-controlled, parallel
      group, multicentre trial. SETTING: Twenty-two clinical centres, including private
      practice groups and academic research clinics. PATIENTS: A total of 530 patients
      between 21 and 80 years of age with essential hypertension were screened for the
      study, and 454 were randomised to treatment with amlodipine 5 mg/benazepril 10
      mg, amlodipine 5 mg, benazepril 10 mg, or placebo for 8 weeks. RESULTS:
      Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in
      sitting diastolic blood pressure than amlodipine 5 mg (P < 0.03), benazepril 10
      mg (P < 0.001), and placebo (P < 0.001). The response rate in the amlodipine 5
      mg/benazepril 10-mg treatment group (66.4%) was better than that observed in the
      amlodipine 5-mg (50.0% P < 0.02), benazepril 10-mg (38.3% P < 0.001), and placebo
      (24.4% P < 0.001) groups. There was no significant difference in heart rate among
      the four groups. The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg
      (1.7%) group was somewhat less than that in the amlodipine 5-mg (4.5%) group.
      CONCLUSIONS: Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and
      was superior to amlodipine 5 mg, benazepril 10 mg, and placebo in reducing
      sitting diastolic blood pressure in patients with essential hypertension.

PMID- 11464261
TI  - Moyamoya disease associated with renovascular disease in a young African
      Brazilian patient.
AB  - Moyamoya is a rare disease characterized by fibrous dysplasia of the internal
      carotid and proximal cerebral arteries, which has been described mainly in young
      Japanese. We present a case of Moyamoya disease with renal artery involvement in
      a young male patient with an African origin. A 15-year-old boy was referred to
      our hospital due to uncontrolled blood pressure, headache, somnolence, cognitive
      deficit and multiple lacunar infarcts in the computed tomography. Cerebral
      arteriography showed the absence of the normal vascular anatomy at the level of
      the circle of Willis. The intracranial vessels presented severe stenosis or were
      occluded and replaced by an extensive network of ectasic collateral vessels.
      Abdominal ultrasound examination identified asymmetric kidneys, and renal
      arteriography showed a tight stenosis of the ostium and proximal segment of right
      main artery, which was only partially relieved by balloon angioplasty. A
      saphenous bypass from aorta to the right renal artery re-established the renal
      blood flow. Blood pressure dropped after surgery and was controlled with low
      doses of diuretic and beta-blocker. After arteriography he presented right
      hemiplegia, with partial recovering in the following months. In conclusion, we
      described the first case of Moyamoya disease with concomitant renovascular
      disease in a young adult of African origin, an association that may be more
      frequent than usually suspected in clinical practice.

PMID- 11464262
TI  - Takayasu--pulseless disease.

PMID- 11464263
TI  - Erythrocyte sodium-lithium countertransport in African American women.

PMID- 11464265
TI  - Monitoring a bioprocess for ethanol production using FT-MIR and FT-Raman
      spectroscopy.
AB  - The application of Fourier transform mid-infrared (FT-MIR) spectroscopy and
      Fourier transform Raman (FT-Raman) spectroscopy for process and quality control
      of fermentative production of ethanol was investigated. FT-MIR and FT-Raman
      spectroscopy along with multivariate techniques were used to determine
      simultaneously glucose, ethanol, and optical cell density of Saccharomyces
      cerevisiae during ethanol fermentation. Spectroscopic measurement of glucose and
      ethanol were compared and validated with the high-performance liquid
      chromatography (HPLC) method. Spectral wave number regions were selected for
      partial least-squares (PLS) regression and principal component regression (PCR)
      and calibration models for glucose, ethanol, and optical cell density were
      developed for culture samples. Correlation coefficient (R(2)) value for the
      prediction for glucose and ethanol was more than 0.9 using various calibration
      methods. The standard error of prediction for the PLS first-derivative
      calibration models for glucose, ethanol, and optical cell density were 1.938 g/l,
      1.150 g/l, and 0.507, respectively. Prediction errors were high with FT-Raman
      because the Raman scattering of the cultures was weak. Results indicated that FT
      MIR spectroscopy could be used for rapid detection of glucose, ethanol, and
      optical cell density in S. cerevisiae culture during ethanol fermentation.

PMID- 11464266
TI  - Effect of physical factors on the production of bacteriocin from Pediococcus
      acidilactici ITV 26.
AB  - The effect of pH, temperature and agitation on growth and bacteriocin production
      by Pediococcus acidilactici ITV 126 was investigated. Experiments were made in
      flasks containing MRS medium at 30 to 40 degrees C, pH 5 to 7 and agitation 0 to
      200 rpm. Factor levels were arranged in a 2(3) factorial design with central and
      axial points. Anova and Tukey paired comparison tests showed that a temperature
      of 35 degrees C favored bacteriocin production, whereas 40 degrees C was best for
      cell growth. A statistical interaction of temperature and agitation was observed
      affecting microbial growth. pH 5 favored both cell growth and bacteriocin
      production.

PMID- 11464267
TI  - Microbial treatment of a styrene-contaminated air stream in a biofilter with high
      elimination capacities.
AB  - A styrene-utilizing mixed microbial culture was isolated and utilized in a
      biofilter for the biological treatment of a contaminated air stream. Biofilter
      media consisted of composted wood bark and yard waste. The biofilters were
      acclimated at 120 s residence time and further evaluated at 60 and 30 s gas
      residence times. The biofilters received organic loading rates of up to 350
      g/m(3) h. The styrene volumetric removal rate was a function of the organic
      loading rate and increased with increasing loading rates. Average volumetric
      removal rates of 69-118 g/m(3) h observed in our studies were higher than
      reported values for styrene biofilters. Average styrene removal efficiencies
      ranged from 65% to 75% (maximum 100%). Axial analysis of styrene concentration
      along the column indicated that the bulk of the styrene removal occurred in the
      first section of the biofilter. Analyses of the media indicated that the moisture
      content of the first section (50-55% w/w) was significantly lower than in the
      second and third sections (65-70% w/w). The pressure drops across the biofilter
      were low due to the high concentration of large media particles. The total
      pressure drops were 1-3, 4-6, and 10-16 mm for the 120-, 60-, and 30-s residence
      time periods, respectively.

PMID- 11464268
TI  - Chromium accumulation by two Streptomyces spp. isolated from riverine sediments.
AB  - Strains designated R22 and R25, isolated from Sali River sediments, Argentina,
      were highly resistant to chromium. These strains were shown by 16S rRNA
      sequencing studies to be Streptomyces spp.; this affiliation was consistent with
      morphological and chemical characteristics. Growth of strains R22 and R25 in
      medium containing 100 mg l(-1) chromate was reduced by only 23% and 34%,
      respectively, compared with growth in medium without added chromium. Streptomyces
      sp. strains R22 and R25 both accumulated chromium with yields of 10.0 and 5.6 mg
      Cr g(-1) of dry weight, respectively, and a chromate concentration of 50 mg ml(
      1). Cell fractionation studies with strain R22 showed that the great majority of
      the chromium were associated with the cell wall fraction. Streptomyces strains
      R22 and R25 may have applications in bioremediation of chromium contamination.

PMID- 11464269
TI  - Effects of amino acid and trace element supplementation on pneumocandin
      production by Glarea lozoyensis: impact on titer, analogue levels, and the
      identification of new analogues of pneumocandin B(0).
AB  - Addition of the amino acids threonine, serine, proline, and arginine to
      fermentations of the fungus Glarea lozoyensis influenced both the pneumocandin
      titer and the spectrum of analogues produced. Addition of threonine or serine
      altered the levels of the "serine analogues" of pneumocandins B(0) and B(5) and
      allowed for their isolation and identification. Proline supplementation resulted
      in a dose-dependent increase in the levels of pneumocandins B(0) and E(0),
      whereas pneumocandins C(0) and D(0) decreased as a function of proline level.
      Moreover, proline supplementation resulted in an overall increase in the
      synthesis of both trans-3- and trans-4-hydroxyproline while maintaining a low
      trans-4-hydroxyproline to trans-3-hydroxyproline ratio compared to the
      unsupplemented culture. Pneumocandin production and the synthesis of
      hydroxyprolines was also affected by addition of the proline-related amino acid
      arginine but not by the addition of glutamine or ornithine. Zinc, cobalt, copper,
      and nickel, trace elements that are known to inhibit alpha-ketoglutarate
      dependent dioxygenases, affected the pneumocandin B(0) titer and altered the
      levels of pneumocandins B(1), B(2), B(5), B(6), and E(0), analogues that possess
      altered proline, ornithine, and tyrosine hydroxylation patterns.

PMID- 11464270
TI  - Salmonella spp. are affected by different levels of water activity in closed
      microcosms.
AB  - Controlling water activity (a(w)) can significantly impact the growth of
      Salmonella in poultry litter and manure - a phenomenon that was studied
      quantitatively using two common serotypes of Salmonella. The quantitative effect
      of changes in levels of a(w) on Salmonella populations was determined using
      inoculated, frosted glass rectangles placed in closed chambers (microcosms).
      Glass rectangles with known concentrations of Salmonella enteritidis and S.
      brandenburg were placed in microcosms maintained at an a(w) level of 0.893 for 24
      h at room temperature (RT) and then transferred to other microcosms maintained at
      the same temperature but with higher a(w) levels (0.932 and 0.987). Salmonella
      populations on the slides were quantified at 4, 18, 24, and 48 h. Slightly
      elevated levels of a(w) (<0.1, i.e., 10% equilibrium relative humidity) for 24 h
      resulted in a 100-fold increase in counts of Salmonella. The data also suggested
      that in vitro adaptation to dry environments may occur when the organisms are
      exposed to alternating levels of relatively high and low (0.987 and 0.893) levels
      of a(w). Any increased tolerance of Salmonella to reduced levels of a(w) could be
      the result of physico-chemical changes in the organism due to selective
      environmental pressure, formation of a protective biofilm, and/or entry into a
      dormant state. Results from this study are compatible with those from previously
      reported on-farm surveys, reinforcing the contention that maintaining a(w) below
      0.85 in and around litter/manure surfaces in poultry or livestock bedding areas
      may be a critical factor in safe production of food.

PMID- 11464271
TI  - Effect of nitrogen source and pH on siderophore production by Rhodotorula strains
      and their application to biocontrol of phytopathogenic moulds.
AB  - The production of rhodotorulic acid, a siderophore synthesized by Rhodotorula
      strains, was improved with the objective of achieving the biocontrol of
      phytopathogenic moulds. Rhodotorulic acid increased up to 60% in the presence of
      urea as a nitrogen source, pH near to 8 and a C:N ratio of 8:1. The siderophore
      containing spent medium showed in vitro antifungal activity against important
      plant pathogens including Botrytis cinerea, which causes grey mould on a wide
      variety of host plants including numerous commercial crops. The antifungal
      activity was related to siderophore concentration.

PMID- 11464272
TI  - Screening and characterization of koji molds producing saline-tolerant protease.
AB  - Three mold strains isolated from soil in the Taipei area of Taiwan were compared
      with a commercial strain of Aspergillus oryzae for their proteolytic activities
      in an 18% NaCl aqueous solution system. Among these strains, the one subsequently
      identified and designated as Aspergillus sp. FC-10 produced protease with
      superior saline tolerance. In aflatoxin tests, this strain did not generate
      detectable aflatoxin after growing on steamed grain polished rice substrate for
      24 days. Two types of extracellular proteases were preliminary fractionated by
      column chromatography on DEAE Sepharose CL-6B. Proteolytic activity of the
      nonadsorbed protease (P-I) was reduced to 9.4% in the 18% NaCl solution compared
      to its original activity determined in the buffer solution. However, the adsorbed
      protease (P-II) was particularly salt tolerant and stable, with 50% proteolytic
      activity retained throughout the 6-h stability test in 18% NaCl solution.

PMID- 11464273
TI  - Protease A activity and nitrogen fractions released during alcoholic fermentation
      and autolysis in enological conditions.
AB  - Determination of protease A activity during alcoholic fermentation of a synthetic
      must (pH 3.5 at 25 degrees C) and during autolysis showed that a sixfold
      induction of protease A activity occurred after sugar exhaustion, well before
      100% cell death occurred. A decrease in protease A activity was observed when
      yeast cell autolysis started. Extracellular protease A activity was detected late
      in the autolysis process, which suggests that protease A is not easily released.
      Evolution of amino acids and peptides was determined during alcoholic
      fermentation and during autolysis. Amino acids were released in early stationary
      phase. These amino acids were subsequently assimilated during the fermentation.
      The same pattern was observed for peptides; this has never been reported
      previously. During autolysis, the concentration of amino acids and peptides
      increased to reach a maximum of 20 and 40 mg N l(-1), respectively. This study
      supports the idea that although protease A activity seemed to be responsible for
      peptides release, there is no clear correlation among protease A activity, cell
      death, and autolysis. The amino acid composition of the peptides showed some
      variations between peptides released during alcoholic fermentation and during
      autolysis. Depending on aging time on yeast lees, the nature of the peptides
      present in the medium changed, which could lead to different organoleptic
      properties.

PMID- 11464274
TI  - Effects of carbon source, phosphorus concentration, and several micronutrients on
      biomass and geosmin production by Streptomyces halstedii.
AB  - The effects of various carbon sources, phosphorus concentration, and different
      concentrations of the micronutrients calcium, cobalt, copper, iron, manganese,
      potassium, and zinc were determined on biomass dry weight production, geosmin
      production, and geosmin/biomass (G/B) values for Streptomyces halstedii, a
      geosmin-producing actinomycete isolated from the sediment of an aquaculture pond.
      Of the substrates tested, maltose as a sole carbon source promoted maximal growth
      by S. halstedii while mannitol promoted maximal geosmin production, and galactose
      yielded the highest G/B values. Fish-food pellets and galactose were poor
      substrates for growth. Increasing phosphorus concentrations enhanced geosmin
      production and G/B values. Of the seven micronutrients tested, zinc, iron, and
      copper had the most profound effects on biomass and geosmin production.
      Increasing zinc concentrations promoted biomass production while inhibiting
      geosmin production and G/B values; increasing concentrations of copper and iron
      inhibited biomass and geosmin production. Increased copper concentrations had the
      greatest effect in preventing growth and geosmin production by S. halstedii.

PMID- 11464275
TI  - Increased erythritol production in fed-batch cultures of Torula sp. by
      controlling glucose concentration.
AB  - The effect of glucose concentration on erythritol production by Torula sp. was
      investigated. The maximum volumetric productivity of erythritol was obtained at
      an initial glucose concentration of 300 g l(-1) in batch culture. The volumetric
      productivity was maximal at a controlled glucose concentration of 225 g l(-1),
      reducing the lag time of the erythritol production. A fed-batch culture was
      established with an initial glucose concentration of 300 g l(-1) and with a
      controlled glucose concentration of 225 g l(-1) in medium containing phytic acid
      as a phosphate source. In this fed-batch culture, a final erythritol production
      of 192 g l(-1) was obtained from 400 g l(-1) glucose in 88 h. This corresponded
      to a volumetric productivity of 2.26 g l(-1) h(-1) and a 48% yield.

PMID- 11464276
TI  - Purification and characterization of a novel salt-tolerant protease from
      Aspergillus sp. FC-10, a soy sauce koji mold.
AB  - A novel salt-tolerant protease produced by Aspergillus sp. FC-10 was purified to
      homogeneity through anion-exchange chromatography, preparative isoelectric
      focusing electrophoresis, and gel filtration chromatography, with an overall
      recovery of 12.7%. This protease demonstrated an optimum pH range of 7.0-9.0 for
      activity, with a stable pH range of 5.0-9.0. The optimum process temperature at
      pH 7.0 was 65 degrees C. The enzyme has a molecular mass of 28 kDa and was
      deduced as a monomer with an isoelectric point of 3.75. Enzyme activity was
      strongly inhibited by 5 mM of HgCl(2) and FeCl(3), and significantly inhibited by
      5 mM of CuSO(4), FeSO(4), and MnCl(2). The activity of this purified protease was
      inhibited by Na(2).EDTA; however, leupeptin, pepstatin A, PMSF, and E-64 did not
      affect the activity. Based on the N-terminal amino acid sequence and amino acid
      composition, this purified protease should be classified as a member of the
      deuterolysin family.

PMID- 11464277
TI  - PHF3-specific antibody responses in over 60% of patients with glioblastoma
      multiforme.
AB  - Glioblastoma multiforme (GBM), a malignant astrocytic tumour, represents the most
      frequent tumour of the human brain. Nevertheless, its molecular pathology is not
      well understood. We utilized the immune system, which contributes to cancer
      protection, to help identify new GBM-related genes. By screening a human GBM cDNA
      library with autologous patient serum (SEREX-approach), we isolated a gene termed
      PHF3 (PHD finger protein 3). The gene product of PHF3 is immunogenic in GBM as
      tested in an allogenic patient serum screening demonstrating antibodies in 24 of
      39 (61.53%) sera, whereas none of the 14 healthy persons had antibodies against
      PHF3. While previous SEREX studies revealed allogenic antibody responses up to
      40%, our results for PHF3 represent the highest reported rate for a specific
      antibody response. We show that GBM patients with an antibody response against
      PHF3 show significant better survival than patients without PHF3-specific
      antibodies. Because the amino acid sequence of PHF3 contains a PHD finger (also
      termed LAP motif), a TFIIS homology, a proline rich region and nuclear
      localization signals, it supposedly functions as a transcription factor. A
      polyclonal antibody generated against PHF3 shows nuclear expression in most
      investigated formalin-fixed, paraffin embedded tissues. In GBM, PHF3 expression
      is concentrated in cells surrounding necroses.

PMID- 11464278
TI  - The periodic down regulation of Cyclin E gene expression from exit of mitosis to
      end of G(1) is controlled by a deacetylase- and E2F-associated bipartite
      repressor element.
AB  - The expression of cyclin E and that of a few other bona fide cell cycle
      regulatory genes periodically oscillates every cycle in proliferating cells.
      Although numerous experiments have documented the role of E2F sites and E2F
      activities in the control of these genes as cells exit from G(0) to move through
      the initial G(1)/S phase transition, almost nothing is known on the role of E2Fs
      during the subsequent cell cycles. Here we show that a variant E2F-site that is
      part of the Cyclin E Repressor Module (CERM) (Le Cam et al., 1999b) accounts for
      the periodic down regulation of the cyclin E promoter observed between the exit
      from mitosis until the mid/late G(1) phase in exponentially cycling cells. This
      cell cycle-dependent repression correlates with the periodic binding of an
      atypical G(1)-specific high molecular weight p107-E2F complex (Cyclin E Repressor
      Complex: CERC2) that differs in both size and DNA binding behaviors from known
      p107-E2F complexes. Notably, affinity purified CERC2 displays a TSA-sensitive
      histone deacetylase activity and, consistent with this, derepression of the
      cyclin E promoter by trichostatin A depends on the CERM element. Altogether, this
      shows that the cell cycle-dependent control of cyclin E promoter in cycling cells
      is embroiled in acetylation pathways via the CERM-like E2F element.

PMID- 11464279
TI  - CCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma
      cells is p53-independent but may involve enhanced cytochrome c release.
AB  - Death ligands such as CD95 ligand (CD95L) or tumor necrosis factor-related
      apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) induce apoptosis in
      radiochemotherapy-resistant human malignant glioma cell lines. The death
      signaling TRAIL receptors 2 (TRAIL-R2/death receptor (DR) 5) and TRAIL-R1/DR4
      were expressed more abundantly than the non-death-inducing (decoy) receptors
      TRAIL-R3/DcR1 and TRAIL-R4/DcR2 in 12 human glioma cell lines. Four of the 12
      cell lines were TRAIL/Apo2L-sensitive in the absence of a protein synthesis
      inhibitor, cycloheximide (CHX). Three of the 12 cell lines were still TRAIL/Apo2L
      resistant in the presence of CHX. TRAIL-R2 expression predicted sensitivity to
      apoptosis. Coexposure to TRAIL/Apo2L and cytotoxic drugs such as topotecan,
      lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, CCNU) or temozolomide
      resulted in synergistic killing. Synergistic killing was more often observed in
      cell lines retaining wild-type p53 activity (U87MG, LN-229) than in p53 mutant
      cell lines (LN-18, T98G, U373MG). Drug exposure resulted in enhanced TRAIL-R2
      expression, but decreased TRAIL-R4 expression in U87MG cells. Ectopic expression
      of dominant-negative p53(V135A) abrogated the drug-induced changes in TRAIL-R2
      and TRAIL-R4 expression, but had no effect on synergy. Thus, neither wild-type
      p53 function nor changes in TRAIL receptor expression were required for synergy.
      In contrast, synergy resulted possibly from drug-induced cytochrome c release
      from mitochondria, serving as an amplifier of the TRAIL/Apo2L-mediated cascade of
      caspase activation. These data provide novel insights into the role of the
      TRAIL/Apo2L system in malignant gliomas and illustrate that TRAIL/Apo2L-based
      immunochemotherapy may be an effective therapeutic strategy for these lethal
      neoplasms.

PMID- 11464280
TI  - Connexin43 suppresses proliferation of osteosarcoma U2OS cells through post
      transcriptional regulation of p27.
AB  - Many lines of evidence indicate that connexin genes expressing gap junction (GJ)
      proteins inhibit tumor cell proliferation. However, the precise molecular
      mechanisms remain unclear. In this study, we show that overexpression of
      connexin43 (Cx43) suppressed proliferation of human osteosarcoma U2OS cells
      through inhibition of the cell cycle transition from G1 to S phase. This
      inhibition was attributed to a significant accumulation of the hypophosphorylated
      retinoblastoma (Rb) protein, which was causally related to decreases in the
      kinase activities of cyclin-dependent kinases (CDKs) 2 and 4. Enforced Cx43
      expression markedly increased the level of the CDK inhibitor p27. This increase
      resulted from an increased synthesis and a reduced degradation of the p27
      proteins, but not influence of the p27 mRNA. Moreover, we show that the Cx43
      modulated GJ function was the main contributor to the elevation in p27 levels, in
      which cAMP was involved. These data suggest that Cx43 appears to inhibit
      proliferation of U2OS cells by increasing the levels of p27 proteins via post
      transcriptional regulatory mechanisms.

PMID- 11464281
TI  - Identification of candidate genes on chromosome band 20q12 by physical mapping of
      translocation breakpoints found in myeloid leukemia cell lines.
AB  - Deletions of the long arm of chromosome 20 have been reported in a wide range of
      myeloid disorders and may reflect loss of critical tumor suppressor gene(s). To
      identify such candidate genes, 65 human myeloid cell line DNAs were screened by
      polymerase chain reaction (PCR) for evidence of allelic loss at 39 highly
      polymorphic loci on the long arm of chromosome 20. A mono-allelic pattern was
      present in eight cell lines at multiple adjacent loci spanning the common deleted
      regions (CDRs) previously defined in primary hematological samples, suggesting
      loss of heterozygosity (LOH) at 20q. Fluorescence in situ hybridization (FISH)
      was then performed using a series of yeast artificial chromosomes (YACs) ordered
      in the CDR, and in five of eight cell lines, the deletions resulted from
      cytogenetically detectable whole chromosomal loss or large interstitial deletion,
      whereas in another cell line deletion was associated with an unbalanced
      translocation. LOH in the CMK megakaryocytic cell line, which has a
      hypotetraploid karyotype, was associated with a der(20)t(1;20)(q32;q12)x2 leading
      to complete deletion of the CDR. Three additional unbalanced translocations were
      found within the CDR and all three breakpoints mapped to a single YAC. We then
      used a series of P1 artificial chromosomes (PACs) spanning this YAC clone, and
      two PACs produced 'split' signals suggesting that they each span one of these
      breakpoints. Exon trapping using PACs that overlap the breakpoint regions yielded
      portions of six genes and evaluation of these genes as candidate tumor suppressor
      genes is underway. The limited information available about these genes suggests
      that the h-l(3)mbt gene is the most attractive candidate.

PMID- 11464282
TI  - A repetitive element containing a critical tyrosine residue is required for
      transcriptional activation by the EWS/ATF1 oncogene.
AB  - Chromosomal fusion of the N-terminal region of the Ewings Sarcoma Oncogene (EWS
      activation-domain, EAD) to the DNA-binding domains of a variety of cellular
      transcription factors produce oncogenic proteins (EWS-fusion proteins (EFPs))
      that cause distinct malignancies. In EFPs, the EAD acts as a potent
      transcriptional activation domain and this ability is repressed in the context of
      normal, non-tumorigenic, EWS. Trans-activation by the EAD is therefore a specific
      characteristic of EFPs and it is thought that EFPs induce tumorigenesis via
      improper transcriptional activation of cellular genes. Functional elements
      required for transcriptional activation are dispersed throughout the EAD, as are
      thirty-one copies of a Degenerate Hexapeptide Repeat (DHR, consensus SYGQQS).
      This suggests that the EAD contains a highly reiterated functional element
      related to DHRs. Here we show that in the context of EWS/ATF1, the EFP that
      causes malignant melanoma of soft parts, trans-cooperation by small regions of
      the EAD ( approximately 30 residues) results in potent transcriptional activation
      dependent on the conserved tyrosine residues present in DHRs. These findings
      provide the first evidence for a role of DHRs in EAD-mediated trans-activation
      and demonstrate that the EAD represents a novel tyrosine-dependent
      transcriptional activation domain.

PMID- 11464283
TI  - Functional identification of LZTS1 as a candidate prostate tumor suppressor gene
      on human chromosome 8p22.
AB  - Deletions in the 8p21-22 region of the human genome are among the most common
      genetic alterations in prostate carcinomas. Several studies in different tumor
      tissues, including prostate, indicate that there are probably multiple tumor
      suppressor genes (TSGs) present in this region. To identify candidate TSGs on
      8p22 a YAC contig spanning this region was assembled and YAC clones retrofitted
      with a selectable marker (neo) were transferred into rat prostate AT6.2 cells.
      Two overlapping YAC clones showed greatly reduced colony-forming efficiency,
      indicating they may carry a TSG. Two BAC clones encompassing the overlapping
      region also appeared to exert suppressive effects on the growth of AT6.2 cells.
      Database searches for genes mapped to the critical region identified a gene known
      as FEZ1 (LZTS1) as a potential candidate suppressor gene. Subsequent experiments
      showed that over-expression of LZTS1 cDNA inhibited stable colony-forming
      efficiencies of AT6.2, HEK-293 and LNCaP cells. In contrast, LZTS1-transfected
      Rat-1 and RM1 cells were growth-stimulated. Database searches also identified
      additional isoforms of the LZTS1 mRNA, as well as LZTS1 protein domains
      reminiscent of those found in transcription factors. Together these data suggest
      that the LZTS1 gene is involved in the regulation of cell growth and its loss of
      function may contribute to the development of prostatic carcinomas, as well as
      other cancers.

PMID- 11464284
TI  - Homeobox gene Cdx1 regulates Ras, Rho and PI3 kinase pathways leading to
      transformation and tumorigenesis of intestinal epithelial cells.
AB  - The Cdx1 homeobox gene encodes for an intestine-specific transcription factor
      involved in the control of proliferation and differentiation of epithelial cells.
      Although it has been indicated that Cdx1 may act as a proto-oncogene in cultured
      fibroblasts, its direct role in the regulation of intestinal tumorigenesis has
      not been demonstrated. Here we show that expression of Cdx1 in an intestinal
      epithelial cell line (IEC-6) induces anchorage-independent growth in soft agar
      and promotes the formation of adenocarcinoma in vivo. The phenotype of Cdx1
      induced tumors was exacerbated when IEC-6/Cdx1 cells were injected together with
      matrigel containing mitogens and extracellular matrix components. These changes
      were correlated with an increase in the GTP-bound form of Ras, modulation of
      Cdc42 and Rho-A activities, and accumulation of phosphatidyl inositol 3 (PI3)
      kinase products. Moreover, combined inhibition of Ras/Rho and PI3 kinase
      signaling by synthethic inhibitors blocked colony formation of IEC-6/Cdx1 cells
      in soft agar. Taken together, these results demonstrate a direct involvement of
      Cdx1, and its collaboration with Ras, Rho and PI3 kinase pathways, in
      transformation and tumorigenesis of intestinal epithelial cells.

PMID- 11464285
TI  - Blockade of NF-kappaB activity in human prostate cancer cells is associated with
      suppression of angiogenesis, invasion, and metastasis.
AB  - Since the NF-kappaB/relA transcription factor is constitutively activated in
      human prostate cancer cells, we determined whether blocking NF-kappaB/relA
      activity in human prostate cancer cells affected their angiogenesis, growth, and
      metastasis in an orthotopic nude mouse model. Highly metastatic PC-3M human
      prostate cancer cells were transfected with a mutated IkappaBalpha
      (IkappaBalphaM), which blocks NF-kappaB activity. Parental (PC-3M), control
      vector-transfected (PC-3M-Neo), and IkappaBalphaM-transfected (PC-3M
      IkappaBalphaM) cells were injected into the prostate gland of nude mice. PC-3M
      and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node
      metastasis, whereas PC-3M-IkappaBalphaM cells produced slow growing tumors with
      low metastatic potential. NF-kappaB signaling blockade significantly inhibited in
      vitro and in vivo expression of three major proangiogenic molecules, VEGF, IL-8,
      and MMP-9, and hence decreased neoplastic angiogenesis. Inhibition of NF-kappaB
      activity in PC-3M cells also resulted in the downregulation of MMP-9 mRNA and
      collagenase activity, resulting in decreased invasion through Matrigel.
      Collectively, these data suggest that blockade of NF-kappaB activity in PC-3M
      cells inhibits angiogenesis, invasion, and metastasis.

PMID- 11464286
TI  - G1-Cdk activity is required for both proliferation and viability of cytokine
      dependent myeloid and erythroid cells.
AB  - Hematopoietic cytokines are critically required for survival and cell
      proliferation of myeloid and erythroid progenitors. It is poorly understood how
      the apoptotic machinery of progenitor cells senses the absence of specific
      cytokines. Here we show that G1-Cdk activity is essential for cytokine-mediated
      viability of myeloid and erythroid progenitors. Cytokine deprivation is
      associated with rapid downregulation of G1-Cdk activity, cell cycle arrest, and
      apoptosis. Specific inhibition of G1-Cdk activity results in apoptotic cell death
      in the presence of saturating cytokine levels. In contrast, specific cell cycle
      arrest in G2/M does not affect viability. When cell proliferation is arrested by
      cytokine withdrawal, primary erythroid progenitors expressing v-ErbA maintain G1
      Cdk activity and undergo delayed apoptosis. Cdk-inhibitors strongly enhance
      apoptosis in starved v-ErbA cells, indicating that sustained Cdk activity is
      required for protection from apoptosis by v-ErbA.

PMID- 11464287
TI  - Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK)
      modulates cell motility and invasion.
AB  - We have shown that ER-negative and invasive human breast cancer cell lines MDA-MB
      468 and MDA-MB-231 have constitutively higher mitogen activated protein kinase
      (ERK1&2/MAPK) when compared to the ER-positive and non-invasive MCF-7 human
      breast cancer cells. In MCF-7 cells, TGFalpha stimulation induced only transient
      MAPK activation, leading to a transient increase in cell migration. However, MDA
      231 and MDA 468 cells, TGFalpha stimulation induced sustained MAPK activation,
      which correlated with enhanced cell motility and in vitro invasion. Serum
      stimulation activates ERK/MAPK activity persistently in both ER-positive and ER
      negative breast cancer cells, leading to enhanced and sustained cell migration.
      Inhibition of MAPK activation by anti-sense MEK expression in MDA-MB-468 cells
      significantly inhibits cell migration and in vitro invasion. In contrast, MCF-7
      cells expressing constitutively activated MEK show a significant increase in MAPK
      activity and cell migration, but this failed to enhance in vitro invasion. The
      kinetic profiles of MAPK activation and inhibition show a relationship between
      the duration and magnitude of MAPK activation and cell migration in both ER
      positive and ER-negative human breast cancer cells. These studies show that cell
      motility is modulated by the magnitude and the duration of MAPK activation; but
      increased activation of MAPK may not be sufficient to allow in vitro invasion in
      non-invasive MCF-7 breast cancer cells.

PMID- 11464288
TI  - Impaired class II transactivator expression in mice lacking interferon regulatory
      factor-2.
AB  - Class II transactivator (CIITA) is required for both constitutive and inducible
      expression of MHC class II genes. IFN-gamma induced expression of CIITA in
      various cell types is directed by CIITA type IV promoter. The two
      transactivators, STAT1 and IRF-1, mediate the IFN-gamma activation of the type IV
      promoter by binding to the GAS and IRF-E of the promoter, respectively. In
      addition to IRF-1, IRF-2, another member of the IRF family, also activates the
      human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the
      promoter in transient transfection assays. IRF-1 and IRF-2 can co-occupy the IRF
      E of the human CIITA type IV promoter. To understand the effect of loss of IRF-2
      on the endogenous CIITA expression, we assayed for CIITA expression in IRF-2
      knock-out mice. Both basal and IFN-gamma induced CIITA expression were reduced in
      IRF-2 knock-out mice. At least half of the amount of inducible CIITA mRNA depends
      on IRF-2. The reduction of IFN-gamma induced CIITA mRNA in IRF-2 knock-out mice
      was due to the reduction of the type IV CIITA mRNA induction. The reduction of
      basal CIITA mRNA was apparently due to the reduction of CIITA mRNA originating
      from other promoters. These data indicate that IRF-2, like IRF-1, plays a
      critical role in the regulation of the endogenous CIITA gene. The implications in
      understanding the previously described phenotypes of IRF-2 defective mice are
      discussed.

PMID- 11464289
TI  - Multi-faceted analyses of a highly metastatic human lung cancer cell line NCI
      H460-LNM35 suggest mimicry of inflammatory cells in metastasis.
AB  - This study established and characterized low-metastatic revertant and parental
      clones of a highly metastatic human lung cancer cell line, NCI-H460-LNM35
      (hereafter referred to as LNM35). Expression-profiling analysis revealed that up
      regulation of various proinflammatory cytokines and angiogenic chemotactic
      chemokines was present in LNM35. Further, while COX-2 itself is known to be
      inducible in inflammation, COX-2 expression levels correlated well with the
      capabilities of these clones for not only in vitro motility and invasion but also
      in vivo metastasis, and COX-2 inhibitors were shown for the first time to reduce
      lung cancer metastasis in vivo. These findings suggest that lung cancer cells may
      mimic inflammatory cells in the process of metastasis.

PMID- 11464290
TI  - Modulation of p53 dependent gene expression and cell death through thioredoxin
      thioredoxin reductase by the Interferon-Retinoid combination.
AB  - We have shown earlier that the IFN-beta and all-trans retinoic acid (RA)
      combination, but not the single agents, induces death in several tumor cell
      lines. Employing a genetic technique we have identified several Genes associated
      with Retinoid-IFN induced Mortality (GRIM). One of the GRIMs was human
      thioredoxin reductase (TR), a redox enzyme. Since the overexpressed TR augments
      IFN/RA stimulated cell death, we explored the mechanisms of TR-mediated death.
      Here we show that TR augments cell death by upregulating the transcriptional
      activity of p53 tumor suppressor. This process does not involve a physical
      increase in levels of p53. Using redox inactive mutants of TR and its substrate,
      thioredoxin (Trx), we demonstrate that IFN/RA-induced regulation of p53 dependent
      gene expression requires TR and Trx. In contrast-over-expression of wildtype TR
      or Trx augment the p53 dependent gene expression in response to IFN/RA treatment.
      Consistent with these results an increased DNA binding activity of p53 was noted
      in the presence of TR. These studies identify a novel mechanism of p53 mediated
      cell death regulation involving redox enzymes.

PMID- 11464291
TI  - Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and
      malignant mesothelioma and identification of a new 3p21.3 homozygous deletion.
AB  - The beta-catenin gene (CTNNB1) has been shown to be genetically mutated in
      various human malignancies. To determine whether the beta-catenin gene is
      responsible for oncogenesis in thoracic malignancies, we searched for the
      mutation in 166 lung cancers (90 primary tumors and 76 cell lines), one blastoma
      and 10 malignant mesotheliomas (two primary tumors and eight cell lines). Among
      the lung cancers, including 43 small cell lung cancers (SCLCs) and 123 non-small
      cell lung cancers (NSCLCs), we identified four alterations in exon 3, which is
      the target region of mutation for stabilizing beta-catenin. One primary
      adenocarcinoma had a somatic mutation from C to G, leading to an amino acid
      substitution from Ser to Cys at codon 37. Among the cell lines, SCLC NCI-H1092
      had a mutation from A to G, leading to an Asp to Gly substitution at codon 6,
      NSCLC HCC15 had a mutation from C to T, leading to a Ser to Phe substitution at
      codon 45, and NSCLC NCI-H358 had a mutation from A to G, leading to a Thr to Ala
      substitution at codon 75. One blastoma also had a somatic mutation from C to G,
      leading to a Ser to Cys substitution at codon 37. Among the 10 malignant
      mesotheliomas, we identified a homozygous deletion in the NCI-H28 cell line.
      Cloning of the rearranged fragment from NCI-H28 indicated that all the exons
      except exon 1 of the beta-catenin gene are deleted and that the deletion junction
      is 13 kb downstream from exon 1. Furthermore, Northern blot analysis of 26 lung
      cancer and eight mesothelioma cell line RNAs detected ubiquitous expression of
      the beta-catenin messages except NCI-H28, although Western blot analysis showed
      that relatively less amounts of protein products were expressed in some of lung
      cancer cell lines. Our findings suggest that the beta-catenin gene is
      infrequently mutated in lung cancer and that the NCI-H28 homozygous deletion of
      the beta-catenin gene might indicate the possibility of a new tumor suppressor
      gene residing in this region at 3p21.3, where various types of human cancers show
      frequent allelic loss.

PMID- 11464292
TI  - CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB
      contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells.
AB  - The molecular alterations in tumour cells leading to resistance towards apoptosis
      induced by CD95 and TRAIL-receptors are not fully understood. We report here that
      the stimulation of the CD95- and TRAIL-resistant human pancreatic adenocarcinoma
      cell line PancTuI with an agonistic anti-CD95 antibody or TRAIL resulted in
      activation of protein kinase C and NF-kappaB. Inhibition of protein kinase C by
      Go6983 sensitized these cells to apoptotic challenges and strongly diminished
      activation of NF-kappaB by anti-CD95 and TRAIL. Similarly, inhibition of NF
      kappaB by MG132 or by transient transfection with a dominant negative mutant of
      IkappaBalpha restored the responsiveness of PancTuI cells to both death ligands.
      In the CD95 and TRAIL-sensitive cell line Colo357 the induction of protein kinase
      C and NF-kappaB following activation of CD95 and TRAIL-R was very moderate
      compared with PancTuI cells. However, pre-incubation of these cells with PMA
      strongly reduced their apoptotic response to anti-CD95 and TRAIL. Taken together,
      we show that activation of protein kinase C operates directly in a death receptor
      dependent manner in PancTuI cells and protect pancreatic tumour cells from anti
      CD95 and TRAIL-mediated apoptosis by preventing the loss DeltaPsim and Cytochrome
      c release as well as by induction of NF-kappaB.

PMID- 11464293
TI  - Translation of the human c-myc P0 tricistronic mRNA involves two independent
      internal ribosome entry sites.
AB  - The human c-myc proto-oncogene is transcribed from four alternative promoters
      (P0, P1, P2, and P3) giving rise to mRNAs having 5' leader sequences of various
      length. The c-myc P0 mRNA contains three open reading frames (ORFs), the last one
      encoding c-Myc1 and c-Myc2 proteins generated by alternative translation
      initiated at CUG and AUG codons. The middle ORF (MYCHEX1) and the 5' ORF (ORF1)
      code for proteins 188 and 114 amino acids in length, respectively. We and others
      previously identified an internal ribosome entry site (IRES) in P0 and P2 c-myc
      mRNAs, promoting the cap-independent translation of c-Myc1 and c-Myc2. Here, we
      report the presence of a second IRES (named IRES1) promoting the cap-independent
      translation of MYCHEX1 in c-myc P0 mRNA. Using deletion analysis, we mapped an 80
      nt region essential for IRES1 activity. c-myc P0 mRNA is thus the first
      eukaryotic polycistronic mRNA described for which translation initiation of two
      different open reading frames (MYCHEX1 and c-Myc1/c-Myc2) involves internal
      ribosome entry.

PMID- 11464294
TI  - Where next for public health in England and Wales?

PMID- 11464295
TI  - Social and demographic factors predictive of change over seven years in CHD
      related behaviours in men aged 18-49 years.
AB  - It is possible that the relationship of social status to coronary heart disease
      is partly mediated through health-related behaviours that have been found to
      relate to both social status and CHD. Changes in certain health-related
      behaviours are known to lead to changes in CHD incidence. What are the
      characteristics of men who change or do not change these behaviours and their
      subsequent chances of CHD? This study aims to relate changes in men's CHD-related
      behaviours over a seven-year period to their social and demographic
      characteristics.A survey was carried out on a random sample of adults in Great
      Britain in 1984-85 and the equivalent information was obtained again on those
      participants who were re-interviewed seven years later in 1991-92. Results are
      presented for the 582 men aged 18-34 and the 584 men aged 35-49 at the first
      interview who were re-interviewed seven years later. Changes over the seven years
      in smoking, saturated fat intake, alcohol consumption and exercise were related
      to social and demographic factors. The two age groups showed broadly similar
      patterns of behaviour. In both age groups, those who continued with or took up a
      low fat diet and/or exercise were more likely to be in a higher social class, in
      employment, to live in private housing and to have more educational
      qualifications. For the younger men only, those in private housing were more
      likely to reduce the amount they smoked. Other findings are also reported. The
      findings suggest that those people who are in less advantageous social and
      economic situations are less likely to change to a more healthy lifestyle and so
      should be a focus for health education.

PMID- 11464296
TI  - Understanding of heart disease and diabetes in a South Asian community: cross
      sectional study testing the 'snowball' sample method.
AB  - South Asian people living in the UK have a higher rate of heart disease and non
      insulin-dependent diabetes. Research into health knowledge and beliefs around
      these diseases is lacking. Accessing South Asian communities is difficult and is
      a barrier to research. We have undertaken a cross-sectional survey of South Asian
      people living in South Tyneside (UK) in 1996 based on a snowball sample to assess
      understanding of heart disease and diabetes. 334 South Asian men and women aged
      16-74 y were interviewed. For heart disease, 115 (35%) people said they did not
      understand the meaning of the term, 62 (19%) were unable to provide any
      description, 48 (14%) could not give a single cause, and 54 (17%) could not
      suggest a preventive measure. For diabetes, 92 (28%) people did not understand
      the term, 43 (13%) could not provide any description, 75 (22%) were unable to
      suggest any risk factor and 64 (20%) could not give a preventive measure. For
      both heart disease and diabetes, two-thirds of respondents said they did not
      understand enough about the conditions to prevent them. There were important
      differences by sex and country of origin on the level of understanding with women
      and Bangladeshi people having lower levels of knowledge. Three of 20 people
      diagnosed with heart disease knew no preventive measure, and of 16 people with
      diabetes, six could not name any risk factors for diabetes. There is a major,
      urgent need for education within the South Asian communities on the causes and
      prevention of heart disease and diabetes.

PMID- 11464297
TI  - Coronary heart disease risk factors in urban bus drivers.
AB  - The purpose of this study was to determine the risk factors for coronary heart
      disease (CHD) in 2297 bus drivers and skilled workers from the Taipei Municipal
      Bus Administrative Bureau. Data for this study were compiled from the medical
      records of annual physical examinations for bus drivers and skilled workers
      conducted at Taipei Municipal Chronic Disease Hospital during the period from
      July 1998 to June 1999. The results showed that, after adjustment for age,
      hypertension rates for bus drivers (56.0%, 986/1361) were significantly greater
      than for skilled workers (30.6%, 164/536). All age groups demonstrated a similar
      difference. Significant differences were also noted in body mass index, serum
      cholesterol, serum triglyceride and ischemic heart disease between bus drivers
      and skilled workers. Among bus drivers, the prevalence of obesity was 9.6%,
      hypercholesterolemia 34.0%, hypertriglyceridemia 69.4% and ischemic heart disease
      1.7%. By contrast, among skilled workers, the prevalence of obesity was only
      4.6%, hypercholesterolemia 29.9%, hypertriglyceridemia 30.6% and ischemic heart
      disease 0.9%. These findings suggest that exposure to the occupation of driving a
      bus may carry an increased risk of CHD and that drivers who develop signs of
      cardiovascular illness should be transferred to non-driving occupations within
      the company.

PMID- 11464298
TI  - Work experience and drinking behavior: alienation, occupational status, workplace
      drinking subculture and problem drinking.
AB  - This study explored the association between alienating job conditions and problem
      drinking within the context of occupational status and workplace drinking
      subculture. From December 1994 to March 1995, a questionnaire survey was
      implemented in the manufactory sector in southern Taiwan. Within the
      questionnaire, any perceived self-estrangement, powerlessness and social
      isolation that the individual experienced in his work were measured as the
      alienating job conditions, and any negative physical, psychological and social
      consequences the individual experienced during the previous month were considered
      as affecting problem drinking. Of the 1117 subjects, 668 (61.8%) reported
      imbibing one or more drinks during the preceding month; the average daily alcohol
      consumption being 0.2+/-0.9 drinks. In addition, 188 (16.8%) subjects reported
      having experienced drinking-related problems in the preceding month. Workers with
      low occupational status were more likely to become problem drinkers when they
      felt comparatively self-estranged in their work. Further, those with a family
      history including any habitual drinker or those under more encouraging workplace
      drinking subculture were more likely to have drinking-related problems. For the
      prevention of problem-related drinking behavior, the workplace should be
      considered as the focus of our future intervention and management program.

PMID- 11464299
TI  - Priority setting with Health Inequality Impact Assessment.
AB  - The imperative to reduce health inequalities whilst keeping within budget means
      that Health Authorities must prioritise to gain maximum benefit from available
      resources. Health Inequality Impact Assessment (HIIA) rapid appraisal has been
      developed by Bro Taf Health Authority to ensure that planning produces positive
      effects for disadvantaged people. HIIA rapid appraisal consists of assessing the
      effect of deprivation on the planning topic, examining the relevant evidence,
      defining opportunities for action and rating these relative to their likely
      impact on health inequalities. The process is best carried out by a
      multidisciplinary team including health authority, local authority, voluntary
      sector and community representatives. This paper describes a HIIA rapid appraisal
      process, that resulted in a Trust that serves a highly disadvantaged locality
      agreeing to try a new method of working and to collaborate in research on
      breaking the cycle of deprivation.

PMID- 11464300
TI  - The control chart: an epidemiological tool for public health monitoring.
AB  - The objective of the authors is to apply the control chart, a statistical method
      for quality control used in industry, to public health surveillance. A pilot
      study was conducted during the 1998 World Football Cup (WFC) by 553 sentinel
      general practitioners (GPs) throughout France. The average number of cases of
      communicable, environmental and societal diseases relating to mass gatherings,
      and the total number of referrals to hospital reported daily by a GP, were
      plotted on a u-chart for each condition monitored. This average was beyond the
      statistical control limits if it fell outside the 99.7% confidence interval of
      the baseline incidences estimated before the WFC. Seven hundred and forty data
      points representing 262 279 medical encounters were plotted. Nineteen points
      exceeded the statistical control limits. None of these alerts was confirmed for
      two consecutive days. Control charts ensured that the level of the items chosen
      for general community health surveillance remained under control.

PMID- 11464301
TI  - Do all patients in primary care who may benefit from eradication of Helicobacter
      pylori have access to effective care?
AB  - The purpose of this study was to identify those patients who would benefit from
      eradication therapy for Helicobacter pylori and to understand the scale of
      service changes needed to implement eradication therapy. All general practices in
      Bradford Health Authority were invited to take part in the study. Patients who
      had received more than one repeat prescription for proton pump inhibitors or H(2)
      receptor antagonists in the previous twelve months were identified using the
      repeat prescription systems in the participating practices. Their case notes were
      examined and the relevant data items extracted by a trained project worker. Forty
      four out of 100 practices agreed to take part and they accounted for a population
      of 262 647 people. Of that population, 2.3% (6037) of patients were on long-term
      acid suppressing treatment. Seventy-nine percent (n=4784) of patients on long
      term acid suppression had a diagnosis recorded in the records; 17% (n=1028) had
      duodenal ulcer; 5% (n=278) gastric ulcer and the rest, 58% (n=3478), consisted of
      patients labelled as dyspepsia, heartburn, gastritis, and non-ulcer dyspepsia.
      Only 131 (10%) of those patients with peptic ulcer had been prescribed
      eradication therapy. Endoscopy and barium meal examinations had been used to
      confirm the diagnosis in 2715 patients. In the remaining patients there was no
      information in the case notes to suggest whether the diagnosis had been confirmed
      by investigations.A substantial proportion of patients previously diagnosed as
      having peptic ulcer have not been offered eradication therapy demonstrating a
      delay in getting research evidence into practice. To ensure all patients within a
      health district who may benefit from eradication therapy, do benefit, a
      systematic approach including access to additional investigative facilities is
      required.

PMID- 11464302
TI  - Hepatitis B among homeless and other impoverished US military veterans in
      residential care in Los Angeles.
AB  - Findings are presented for a cross-sectional study of serological markers of
      hepatitis B virus (HBV) infection in an underserved population-impoverished
      veterans of the US armed forces in a Veterans Administration (VA) residential
      program in the US. We examine the demographic, background, and risk factors
      associated with HBV infection in this high-risk population. This paper presents a
      secondary analysis of cross-sectional survey and clinical data for 370 male
      veterans who were residents of a domiciliary care program for homeless veterans
      in Los Angeles, using chi(2), Fisher's Exact, and logistic regression analysis.
      About one-third (30.8%) of the sample tested positive for current or past HBV
      infection (ie, seropositive for either the HBV core antibody or surface antigen).
      After multivariate analysis, rates of HBV were significantly higher among
      veterans who were older, non-white, or who had a history of regular heroin use (a
      proxy measure for injection drug use), drug overdose, or drug detoxification
      treatment. The rate of current or past HBV infection among veterans in this
      sample (30.8%) was high compared to an estimated 5% to 8% of the general US
      population. Also, 3% of the sample were currently infected with HBV. Strategies
      for intervention include broader screening, immunization, and treatment
      interventions with this high-risk group.

PMID- 11464303
TI  - Management of childhood gastroenteritis in the community.
AB  - Good evidence-based research exists for the management of gastroenteritis.
      However, we encountered local anecdotal evidence of wide variations in the
      management of gastroenteritis. In order to assess the prevailing practice in
      gastroenteritis management in primary care, in the Tees Health region, an
      anonymous questionnaire study involving general practitioners (GPs) and health
      visitors (HVs) was performed. Three case scenarios were presented in the
      questionnaire, involving a breast-fed infant, a formula-fed infant and a four-y
      old child all with diarrhoea and vomiting, but able to tolerate oral fluids and
      not ill enough to need hospital admission. Most GPs (78.6%) and HVs (80.5%)
      advised continuation of breast-feeding, though the practice of giving advice to
      stop breast-feeding, starve the child and substitute inappropriate fluids such as
      flat coke, was still common. For infants who were bottle-fed, this inappropriate
      advice was given much more commonly (only 25.6% and 52.8% of GPs and HVs,
      respectively gave advice to continue bottle-feeding). This was even more true for
      the four-y-old, for whom advice to continue with a normal diet was very much the
      exception (7.7% of GPs and 19.5% of HVs). Advice given to parents of children
      with gastroenteritis was inconsistent and, in many cases, inappropriate. This has
      implications for clinical governance. There is an urgent need for the development
      and implementation of local guidelines.

PMID- 11464304
TI  - A report of an outbreak of Shigellosis in a primary school in Staffordshire.
AB  - This paper describes the management of an outbreak of Shigellosis, reported in
      the national media, in a village school in Staffordshire. The issues encountered
      by the outbreak team during the management of this incident have re-affirmed the
      need for public and environmental health departments to work closely with
      educational bodies to develop clear and consistent action plans for the
      management of communicable disease outbreaks. The management of communicable
      disease in schools, the workplace and other settings should be addressed,
      possibly as a component of local health improvement plans.

PMID- 11464305
TI  - Quantitative microbial monitoring in a dental office.
AB  - The aim of this study was to evaluate the environmental pollution before and
      after dental procedures (during one year) in a dental office in which a system of
      air filtration was effective and suitable procedures of microbial controls were
      routinely applied for instruments and small surfaces. The air contamination was
      evaluated during one year by the 'plate' method (Air Microbial Index, AMI) in
      each room of the dental office following a bimonthly monitoring program. Nutrient
      agar plates were exposed, in monitored areas for 1 h for each control time and
      incubated at 37 degrees C for 2 days. The number of viable cells was expressed as
      colony forming units per plate per hour (CFU/plate/h). During the observation
      year, the quantitative analysis of the microbiological levels in the operative
      areas was always within acceptable values. In fact, a range from 4-18 CFU/plate/h
      was found as the mean of AMI in each controlled room. In particular, the aerosol
      pollution following dental procedures did not significantly modify AMI values
      compared with AMI values recorded before dental procedures. Data presented here
      demonstrate that the combined use of effective infection control procedures and a
      system of air filtration can be efficacious in reducing airborne environmental
      contamination in a dental office and emphasise the use of an inexpensive method
      such as AMI to verify the environmental bacterial pollution.

PMID- 11464308
TI  - Towards a catheter free status in neurogenic bladder dysfunction: a review of
      bladder management options in spinal cord injury (SCI).
AB  - STUDY DESIGN: Review. OBJECTIVES: To assess current available options for bladder
      management in SCI patients the post-acute phase. METHODS: Relevant articles were
      extracted from medline and Cinahl between 1966--1999. In addition, references
      earlier than 1966 that were listed in these articles were identified and
      extracted. RESULTS: Catheterisation (indwelling or self intermittent) is still
      carried out by the majority of SCI patients with more morbidity for indwelling
      catheterisation. Other methods include condom drainage, suprapubic tapping and
      supreapubic pressure are used and are associated with less complications.
      Complicated procedures like sacral anterior root stimulator and entero
      cystoplasty are carried out with the onset of or impending complications.
      CONCLUSION: Several methods of bladder management are available in the post-acute
      phase of SCI. The method used has to be based on urodynamic characteristics with
      the aim of producing a continent bladder with adequate low pressure storage
      capacity. Modern management of the bladder in SCI has successfully reduced renal
      related mortality in SCI from 95% in the first half of the 20th century to the
      present 3%.

PMID- 11464309
TI  - Surgical treatment for thoracic spinal stenosis.
AB  - OBJECTIVES: To describe the underlying causes, surgical results and prognostic
      factors in thoracic stenosis causing myelopathy. METHODS: The underlying causes
      and surgical results were analyzed retrospectively in 28 cases of thoracic spinal
      stenosis which caused myelopathy. Degenerative spondylosis was the most common
      cause, and three cases were associated with systemic diseases. Decompressive
      laminectomy was performed in 24 cases, anterior decompression in five cases, and
      combined decompression in one case. Ossification of ligamentum flavum was found
      in 18 cases, facet hypertrophy in 13, ossification of posterior longitudinal
      ligament in six, and ventral spur in four. Postoperatively 16 patients improved
      and four patients worsened. Follow-up ranged from 2 months to 5 years and 8
      months). Statistical analysis was performed using a chi(2) test to investigate
      the relationship between subjects. Multivariant analysis (general linear model)
      was used to determine the factors which influence surgical outcome. RESULTS:
      There were neurological improvements in 16 patients, in whom Nurick grade changed
      from 3.3 preoperatively to 1.8 postoperatively. Eight patients showed no
      significant change in functional grade and four patients deteriorated after
      decompressive laminectomy. The group of which initial symptom duration was less
      than 2 years showed better results (P=0.006). The group with sufficient
      decompression and no additional proximal stenosis had better treatment outcome
      (P=0.005, P=0.002). CONCLUSION: Chronic severe myelopathy caused by thoracic
      spinal stenosis can be reversible with appropriate decompression. Surgical
      outcome was dependent on initial symptom duration, sufficient decompression and
      presence of additional proximal stenosis. SPONSORSHIP: This study was supported
      by a grant No. 02-1997-071-0 from the Seoul National University Hospital Research
      Fund.

PMID- 11464310
TI  - Prevention of heterotopic ossification after spinal cord injury with
      indomethacin.
AB  - STUDY DESIGN: A randomized, prospective, double-blind, placebo-controlled
      clinical trial. OBJECTIVES: To determine the effect of indomethacin on the
      prevention of heterotopic ossification (HO) following spinal cord injury (SCI).
      SETTING: County Hospital, Miami, Florida, USA. METHODS: Sixteen patients were
      treated with slow-release indomethacin 75 mg daily and 17 patients received
      placebo for a period of 3 weeks. Prevention was started 21+/-14 days after SCI.
      In both groups of patients there was similar age of the patients as well as the
      level of SCI and ASIA impairment scale. Two methods were used to diagnose HO,
      bone scintigraphy and radiographic examination. Bone scintigraphy with technetium
      labeled methylene-diphosphonate was used for diagnosis of early stage, while
      radiography was used for diagnosis of late stage of HO development. RESULTS: A
      significantly lower incidence of early HO was found in the indomethacin group
      (25%) than in the placebo group (65%; P<0.001). Similarly there was a significant
      reduction of late HO in the indomethacin group (12.5%) as compared to the placebo
      group (41%; P<0.001). CONCLUSION: Our data suggest that indomethacin used during
      the first 2 months after SCI is effective in prevention of HO in a significant
      number of patients.

PMID- 11464311
TI  - Impact of age on the injury pattern and survival of people with cervical cord
      injuries.
AB  - STUDY DESIGN: A retrospective, follow-up study. OBJECTIVES: To differentiate the
      injury pattern and survival of people with cervical cord injuries with onset at
      different ages. SETTING: Rehabilitation wards of a university hospital that is a
      tertiary referral center in Taipei, Taiwan. METHODS: The records of acute and
      traumatic cervical cord injury patients hospitalized from 1989 to 1997 were
      reviewed. All subjects received comprehensive rehabilitation programs during
      hospitalization. Their survival status at the end of follow-up was studied.
      RESULTS: Forty-seven of 109 (43.1%) people with cervical cord injuries were 50
      years or older at onset. Older patients were more frequently injured by minor
      falls, resulting in more incomplete quadriplegia. They also showed fewer spinal
      fractures, and more demonstrated associated spondylosis and ossification of the
      posterior longitudinal ligament. Eleven (10.2%) subjects were deceased, found by
      a linkage to a death registration database at the end of follow-up. The
      significant predictor of survival status at follow-up was older age at injury
      using Cox proportional hazards model. CONCLUSION: Spinal cord injured patients
      had different injury patterns, demanding different preventative strategies. Those
      injured at older ages were at higher risk of mortality according to our study.
      SPONSORSHIP: This study was supported in part by grants from the National Taiwan
      University Hospital (89S2005), Taipei, Taiwan.

PMID- 11464312
TI  - Evaluation of post traumatic distress in the first 6 months following SCI.
AB  - STUDY DESIGN: Cross-sectional questionnaire. OBJECTIVES: To assess the degree of
      post traumatic stress symptomatology and its correlates amongst a group of new
      spinal cord injured patients. SETTING: The National Spinal Injuries Centre, Stoke
      Mandeville Hospital NHS Trust. METHOD: Eighty-five participants with an average
      age of 32.6 years were assessed between 6 and 24 weeks post injury. Seventeen
      participants were female. Seventy per cent had complete lesions. Forty per cent
      had paraplegia and 60% had tetraplegia. Road traffic accidents were the most
      common cause of injury followed by falls and then sporting accidents. The Impact
      of Event Scale was used to measure the experience of intrusive thoughts about the
      trauma and avoidance of trauma related stimuli. Anxiety (SAI), depression (BDI)
      and dependency (FIM) were also measured. RESULTS: High levels of distress were
      evident in 14% of the sample. Trauma-related distress was significantly higher in
      female patients or patients with high levels of anxiety or depression.
      CONCLUSION: In this sample, the rates of trauma-related distress following spinal
      cord injury were comparable to those found following other traumas and are of
      clinical significance.

PMID- 11464313
TI  - Life satisfaction in persons with spinal cord injury: a comparative investigation
      between Sweden and Japan.
AB  - STUDY DESIGN: A cross-sectional and comparative investigation using the unified
      questionnaire. OBJECTIVES: To investigate the cultural (East Asian versus North
      European) differences in life satisfaction between long-term survivors of spinal
      cord injuries (SCI). SETTING: Uppsala county in Sweden and Fukuoka prefecture in
      Japan. METHODS: A questionnaire dealing with life satisfaction was prepared by
      the authors. It focused mainly on sexual life and accompanied a self-rating
      Barthel Index Score. The questionnaire was mailed to male SCI persons in the two
      communities, Uppsala county (Sweden) and Fukuoka prefecture (Japan). Forty (77%)
      Swedish and 85 (71%) Japanese SCI replied. RESULTS: (1) Swedish SCI appeared to
      be more satisfied than Japanese SCI in general health, economy, social activity,
      social service, family life and sexual life. (2) Several life domains indicated
      significant difference in life satisfaction between with- and without-partner
      group in Japanese SCI. No life domains indicated significant difference in
      Swedish SCI. (3) No statistically significant difference was indicated in all of
      life domains between the degree of life satisfaction and interval since spinal
      cord damage. CONCLUSION: The more expanded cross-cultural study is expected to be
      helpful for discussing the QOL of SCI.

PMID- 11464314
TI  - Occlusion of left common iliac vein by a distended urinary bladder in a male with
      paraplegia due to spinal cord injury.
AB  - STUDY DESIGN: A report of a male subject who sustained paraplegia at T-5 level
      due to spinal cord injury (SCI) 18 years ago, and in whom, occlusion of the left
      common iliac vein by a distended bladder was detected during a routine follow-up.
      OBJECTIVES: To illustrate a rare complication of chronic distension of the
      urinary bladder viz occlusion of the left common iliac vein, which persisted even
      after providing adequate bladder drainage by intermittent catheterisation.
      SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: As part of a
      routine follow-up, we performed intravenous urography by injecting 50 ml of
      Ultravist 300 in a vein over the dorsum of the left foot. Opacification of
      collateral veins in the pelvis was seen in the 5- and 10-min films, which
      suggested iliac venous occlusion. In order to confirm the diagnosis, contrast was
      injected intravenously in the left foot and venography was performed. RESULTS:
      Venography revealed a distended left common iliac vein with contrast flowing into
      the right internal iliac vein through collateral veins in the pelvis; the right
      common iliac vein and inferior vena cava were patent. Duplex Doppler sonography
      showed compression of left common iliac vein by the posterior wall of a distended
      bladder with absence of blood flow through the compressed segment. Computerised
      tomography (CT) confirmed the diagnosis of extrinsic compression of the left
      common iliac vein against the promontory of sacrum by a distended bladder. CT
      excluded other causes for iliac vein occlusion. CONCLUSION: In a male subject
      with SCI, chronic bladder distension produced occlusion of the left common iliac
      vein. Health professionals caring for individuals with SCI should be aware that
      long-standing bladder distension could cause pressure effects upon adjacent
      structures in the pelvis.

PMID- 11464315
TI  - Synovial cyst at the intervertebral foramina causing lumbar radiculopathy.
AB  - OBJECTIVE: To determine the presence of intraforaminal synovial cysts resulting
      in nerve root compression. METHODS: A 26 year old man presenting with left leg
      pain was admitted. He had no motor, sensory, or reflex changes. Magnetic
      resonance imaging (MRI) and MRI-myelography showed an intra and extra foraminal,
      extradural, cystic lesion at L4 vertebra on the left side. RESULTS: At surgery
      there was a cystic mass pressing on the nerve root, and no connection or
      communication with the dural structures could be found. CONCLUSION: Synovial
      cysts are uncommon extradural degenerative lesions. Intraspinal synovial cysts
      occur most often at the L4-5 level, but they have been reported in all areas of
      the spine except the intraforaminal region and the sacrum.

PMID- 11464317
TI  - Acquired posterior choanal stenosis and atresia: management of this unusual
      complication after radiotherapy for nasopharyngeal carcinoma.
AB  - PURPOSE: To report on acquired posterior choanal stenosis and atresia after
      radiotherapy for nasopharyngeal carcinoma. MATERIALS AND METHODS: Four patients
      with acquired bilateral choanal atresia and 2 with severe unilateral choanal
      stenosis in the posterior choanae were identified after treatment of
      nasopharyngeal carcinoma with radiotherapy. The mean age was 42 years (range, 29
      to 48 years). Two patients had stage II, and 4 had stage III disease, according
      to Ho's classification. They all received a 66 Gy dose of external irradiation
      delivered to the nasopharynx, and a mean dose of 62.6 Gy to the neck. Five
      patients had an additional 20 Gy delivered to the parapharyngeal region, and 1
      patient had intracavitatory brachytherapy of 18 Gy delivered to the nasopharynx.
      The mean onset of symptoms was 10.5 months (range, 2 to 40 months)
      postirradiation. All patients were treated by transnasal endoscopic resection.
      Merocel epsitaxis packing (Medtronic Xomed, Jacksonville, FL) was used to stent
      the nasal airway for 2 weeks postoperatively. RESULTS: The mean follow-up was
      16.2 months (range, 14 to 18 months) after surgery. Four patients (67%) were
      symptom-free. Two patients (33%) had unilateral restenosis in the postnasal space
      that required revision surgery and further nasal stenting for 2 weeks, and both
      were subsequently free from further restenosis. No adverse postoperative
      complication occurred. CONCLUSION: Acquired posterior choanal stenosis and
      atresia is an unusual long-term complication after radiotherapy that can be
      successfully treated with transnasal endoscopic resection. A 2-week Merocel nasal
      stent is recommended to prevent restenosis in the posterior choanae.

PMID- 11464318
TI  - Safety and efficacy of currently available fibrin tissue adhesives.
AB  - PURPOSE: The purpose of this study is to review preparation methods, bonding
      power, preparation time, and costs associated with currently available autologous
      and homologous fibrin tissue adhesive preparations. METHODS: Two autologous
      fibrin tissue adhesive preparations (AFTA-A and AFTA-E), a single-donor
      homologous preparation, and 2 multiple-donor pooled homologous fibrin tissue
      adhesives, Vi-Guard and Tisseel, were evaluated and compared in relation to
      bonding power, preparation time, cost, bicompatibility, and biodegradability.
      RESULTS: Vi-Guard and Tisseel showed significantly greater bonding strengths than
      their single-donor counterparts. AFTA-C offers the quickest preparation time. All
      preparations were found to be similar in biocompatibility and biodegradability in
      soft tissue tests. Histology showed no infection or tissue reaction from adhesive
      exposure in any of the preparations. CONCLUSION: The optimal choice of a fibrin
      tissue adhesive is determined by the particular clinical indication. Currently
      available fibrin tissue adhesives vary appreciably in their bonding strength,
      cost, level of exposure risk, and preparation methods and times. Autologous
      preparations, which offer optimal safety, lack the strength and availability
      characteristics found with the multiple-donor preparations.

PMID- 11464319
TI  - Pharyngeal tuberculosis.
AB  - PURPOSE: To increase awareness of tuberculosis (TB) as an important differential
      diagnosis of lesions in the pharynx and discuss its presentation. PATIENTS AND
      METHODS: The study included nine patients (2 males and 7 females); each with a
      diagnosis of primary pharyngeal tuberculosis (PTB). Of these, 3 had
      nasopharyngeal TB, 5 had tonsillar TB, and 1 had hypopharyngeal TB. The
      diagnostic criteria were either positive culture, positive smear, or
      histopathologic features of caseating granuloma consistent with TB in the biopsy
      specimen and a response to treatment. RESULTS: All patients had primary
      infection. The main presenting symptom in all nasopharyngeal TB was neck mass,
      whereas tonsillar TB patients presented with sore throats or discomfort.
      Dysphagia was the presenting symptom in hypopharyngeal TB. Six patients (3 with
      nasopharyngeal TB and 3 with tonsillar TB) had cervical adenopathy. The smear for
      acid-fast bacillus was positive in 4 patients (44.4%); culture was positive in 2
      patients (22.2%). Histopathologic features of caseating granuloma, consistent
      with TB, were positive in all patients who received antituberculous medications.
      CONCLUSION: Otolaryngologists should consider pharyngeal TB as one of the
      differential diagnosis of lesions of the pharynx especially in those countries
      where TB is endemic.

PMID- 11464320
TI  - Meniere's disease as a manifestation of vestibular ganglionitis.
AB  - OBJECTIVE: To present morphologic evidence of viral-induced vestibular nerve
      pathology in Meniere's Disease (MD). MATERIAL STUDIED: Twelve temporal bones (TB)
      from 8 patients with the clinical symptoms of MD. RESULTS: There was
      endolymphatic hydrops (EH) and perilymphatic fibrosis in 10 of the 12 TB from MD
      patients. Of the 10 TB with EH of the pars inferior, 3 also contained
      outpouchings in the pars superior (utricle and canals), and 3 showed apical
      spiral ganglion cell loss. Focal vestibular nerve axonal degeneration was
      observed in all but one TB. CONCLUSION: Morphologic changes in TB of patients
      with MD, and clinical observations in patients with recurrent vestibulopathy,
      support the concept that the pathologic mechanism responsible for auditory and
      vestibular symptoms in MD may be reactivation of a latent viral vestibular
      ganglionitis.

PMID- 11464321
TI  - Vagal neuropathy after upper respiratory infection: a viral etiology?
AB  - PURPOSE: To describe a condition that occurs following an upper respiratory
      illness, which represents injury to various branches of the vagus nerve. Patients
      with this condition may present with breathy dysphonia, vocal fatigue, effortful
      phonation, odynophonia, cough, globus, and/or dysphagia, lasting long after
      resolution of the acute viral illness. The patterns of symptoms and findings in
      this condition are consistent with the hypothesis that viral infection causes or
      triggers vagal dysfunction. This so-called postviral vagal neuropathy (PVVN)
      appears to have similarities with other postviral neuropathic disorders, such as
      glossopharyngeal neuralgia and Bell's palsy. MATERIALS AND METHODS: Five patients
      were identified with PVVN. Each patient's chart was reviewed, and elements of the
      history were recorded. RESULTS: Each of the 5 patients showed different features
      of PVVN. CONCLUSIONS: Respiratory infection can trigger or cause vocal fold
      paresis, laryngopharyngeal reflux, and neuropathic pain.

PMID- 11464322
TI  - Is glutathione-S-transferase-pi expression a reliable predictor of chemoradiation
      response in cancer of the head and neck?
AB  - PURPOSE: Concurrent radiation and chemotherapy is being evaluated as an
      alternative treatment to surgery for patients with advanced squamous cell
      carcinoma of the head and neck, because organ preservation maybe possible without
      compromising survival. However, the response to concurrent chemoradiation
      treatment varies from patient to patient, and there is currently no available
      molecular predictor of response for this particular treatment modality. There is
      some evidence to indicate that glutathione S-transferase-pi (GST-pi), which is
      one of the drug detoxifying enzymes, may decrease the effectiveness of platinum
      based chemotherapy in the treatment of a variety of tumor types. This study was
      performed to investigate whether GST-pi expression was correlated with response
      to concurrent chemotherapy and radiotherapy in patients with advanced squamous
      cell carcinoma of the head and neck. MATERIALS AND METHODS: Diagnostic biopsy
      specimens of 36 patients who underwent concurrent chemoradiotherapy for the
      treatment of advanced squamous cell carcinoma of the head and neck were examined
      for GST-pi expression by using immunohistochemistry with polyclonal antihuman GST
      pi antibodies. GST-pi expression scores were compared among responders and
      nonresponders. RESULTS: Although the staining rate with antiGST-pi was slightly
      lower in the responder group in comparison with the nonresponders (82% vs 100%),
      the difference was not statistically significant. CONCLUSION: GST-pi expression
      is unlikely to be a valuable predictor of response to concurrent chemotherapy and
      radiation treatment in patients with advanced squamous cell carcinoma of the head
      and neck.

PMID- 11464323
TI  - Squamous cell carcinoma metastatic to the neck from an unknown head and neck
      primary site.
AB  - Squamous cell carcinoma metastatic to the neck from an unknown head and neck
      primary site is relatively uncommon and presents a challenging diagnostic and
      therapeutic dilemma. Diagnostic evaluation includes fine-needle aspiration of the
      neck mass, chest roentgenography, computed tomography, and/or magnetic resonance
      imaging of the head and neck, followed by panendoscopy and biopsies. The primary
      tumor will be detected in approximately 40% of patients; approximately 80% of
      cancers are located in the base of the tongue or tonsillar fossa. Management
      options include treatment of the neck alone or both sides of the neck and the
      potential head and neck primary sites. The latter approach is associated with
      better long-term control above the clavicles. The 5-year survival rate is
      approximately 50% after treatment and is influenced by the extent of neck
      disease. In this article, we review the pertinent literature.

PMID- 11464324
TI  - An update on inflammatory disorders of the pediatric airway: epiglottitis, croup,
      and tracheitis.
AB  - Acute infections of the respiratory tract are common in pediatric patients.
      Respiratory disease is the leading cause of hospitalization in children less than
      4 years of age and is responsible for many physicians' office and emergency
      department visits.(1) The severity of upper respiratory tract infection ranges
      from mild, self-limited disease to potentially life-threatening airway
      obstruction. The prepared clinician can often make a diagnosis based solely on
      the history and physical examination, using radiographs and laboratory
      examinations to aid in diagnosis when the clinical picture is unclear. At times,
      airway collapse is imminent, and the clinician must proceed directly to endoscopy
      for definitive diagnosis and airway protection. This article will discuss the
      pathogenesis, clinical presentation, and management of epiglottitis, croup, and
      bacterial tracheitis in the pediatric population.

PMID- 11464325
TI  - Lingual thyroid: iodine 131: a viable treatment modality revisited.
AB  - PURPOSE: Lingual thyroid has a reported incidence between 1:10 and 1:100,000.
      When symptomatic, patients may present with dysphagia, choking, and/or dyspnea.
      Current surgical treatment options range from tumor extirpation or transposition
      to excision and reimplantation. Tracheotomies are often performed postoperatively
      for reliable airway control. Iodine 131 (131I) has not been a popular modality of
      treatment for lingual thyroid because of theoretical fears of increased airway
      obstruction from thyroiditis. We believe that these fears were not substantiated,
      and that symptomatic patients needed a reliable, nonsurgical treatment option.
      Therefore, our goal was to further investigate the use of 131I for the treatment
      of symptomatic lingual thyroid. PATIENTS AND METHODS: A 6-year retrospective
      chart review was performed. From 1994 to 2000, 2 patients with symptomatic
      lingual thyroid presented to the Arkansas Cancer Research Center Head and Neck
      Oncology clinic, University of Arkansas for Medical Sciences, Little Rock, AR.
      Patients underwent pretreatment computed tomography, and iodine 123 scans. They
      then received 1 oral dose of 131I. Doses ranged from 30 to 85 mCi. Patients were
      then followed daily for signs of airway compromise. RESULTS: Complete resolution
      of symptoms was seen 2 months after treatment. Patients did not complain of any
      increased airway compromise during treatment initiation. Patients remain symptom
      free and are maintained on thyroid hormone replacement. CONCLUSIONS: Iodine 131
      ablation of lingual thyroid is a safe and effective treatment in symptomatic
      patients and should be included in the algorithm when formulating a treatment
      plan.

PMID- 11464326
TI  - Glomangiomyoma of the nasal cavity.
AB  - Glomus tumor is a rare neoplasm that typically occurs in soft tissue of the
      extremity, particularly the subungual region of the finger tip. It rarely occurs
      in the nasal septum. Glomangiomyoma is a rare histologic variant of glomus tumor.
      The authors describe a case of glomangiomyoma of the nasal septum that presented
      as nasal obstruction. The histologic, immunohistochemical, and
      electronmicroscopic findings are described. The otolaryngologist and surgical
      pathologist should be aware of such an entity, and should not confuse it with the
      totally unrelated glomus jugulare tumor, or paraganglioma of the middle ear.

PMID- 11464327
TI  - Familial enlarged vestibular aqueduct syndrome.
AB  - Enlarged vestibular aqueduct syndrome is a clinical disease entity associated
      with anatomic abnormality of the bony canal in the temporal bone containing the
      endolymphatic duct and sac. The definition of this syndrome is progressive
      sensorineural hearing loss with an isolated enlarged vestibular aqueduct.
      Familial inheritance of enlarged vestibular aqueduct syndrome is rare, and the
      correct mode of inheritance has not been discovered. This report is the study of
      familial inheritance with enlarged vestibular aqueduct syndrome. Clinical
      audiological, radiographic, and chromosomal analyses were performed in this case,
      which reports on two female probands who are offspring of normal parents.
      According to the study of pedigree, familial inheritance of enlarged vestibular
      aqueduct syndrome is strongly suspected as an autosomal recessive trait. Further
      study should be focused on discovering the genetic evaluation of familial
      inheritance of enlarged vestibular aqueduct syndrome.

PMID- 11464328
TI  - Aneurysmal bone cyst of the frontal sinus.
AB  - Aneurysmal bone cysts are benign, vascular, cystic osseous tumors. Approximately
      2% of all aneurysmal bone cysts are found in the head and neck region, with the
      most common site being the mandible. We report a case of an aneurysmal bone cyst
      arising from the frontal sinus in a pediatric patient. The diagnosis was
      suggested through various radiographic studies, with the final pathologic
      diagnosis confirmed after tumor excision. Complete en-bloc excision was performed
      by using a bifrontal craniotomy approach, with immediate reconstruction of the
      defect by using a split calvarial bone graft.

PMID- 11464329
TI  - Dermal thymus: case report and review of the literature.
AB  - An aberrant thymus is not uncommon; it is usually located in the subcutaneous
      tissue and attaches to deeper structures, but it rarely occurs within the dermis
      (dermal thymus). We report on an 8-month-old male infant with a dermal thymus. He
      was born with a skin tumor on the right side of the neck, located just over the
      sternocleidomastoid muscle. The tumor was soft, dark red, and elevated. It
      measured 10 by 21 mm in diameter. The surface was erosive and partially covered
      with crust. The infant also had a unilateral cleft lip and a deformity of the
      bilateral auricles. Because of recurrent episodes of infection, the tumor was
      resected and histologically diagnosed as a dermal thymus.

PMID- 11464330
TI  - Fibrous dysplasia, chondrosarcoma, and McCune-Albright syndrome.

PMID- 11464331
TI  - Professional organizations: how they work and when they don't.

PMID- 11464332
TI  - Research: Barriers to interdisciplinary research.

PMID- 11464333
TI  - Technology: Intellectual property and technology transfer.

PMID- 11464334
TI  - Professional practice: Bridging the gap.

PMID- 11464335
TI  - Public policy: Realigning our skewed health care system.

PMID- 11464336
TI  - NCLEX-RN performance: predicting success on the computerized examination.
AB  - Since the adoption of the Computerized Adaptive Testing (CAT) format of the
      National Certification Licensure Examination for Registered Nurses (NCLEX-RN), no
      studies have been reported in the literature on predictors of successful
      performance by baccalaureate nursing graduates on the licensure examination. In
      this study, a discriminant analysis was used to identify which of 21 variables
      can be significant predictors of success on the CAT NCLEX-RN. The convenience
      sample consisted of 289 individuals who graduated from a baccalaureate nursing
      program between 1995 and 1998. Seven significant predictor variables were
      identified. The total number of C+ or lower grades earned in nursing theory
      courses was the best predictor, followed by grades in several individual nursing
      courses. More than 93 per cent of graduates were correctly classified. Ninety
      four per cent of NCLEX "passes" were correctly classified, as were 92 per cent of
      NCLEX failures. This degree of accuracy in classifying CAT NCLEX-RN failures
      represents a marked improvement over results reported in previous studies of
      licensure examinations, and suggests the discriminant function will be helpful in
      identifying future students in danger of failure. J Prof Nurs 17:158-165, 2001.

PMID- 11464337
TI  - Strategic development of a master's program on the World Wide Web.
AB  - Quality teaching requires more than masterful professors. In today's academic
      environments, leaders in educational institutions have responsibilities to supply
      fiscal and human resources that support settings conducive to learning and that
      instill human, educational, and professional values. Recent technologic advances
      have shifted the capacities to deliver programs of study outside traditional
      classrooms. The World Wide Web can deliver nursing courses that are complex,
      multimedia, and interactive. Planning to offer a degree program on-line requires
      examining the organization's mission and philosophy as well as allocating human
      and fiscal resources to the project. As leaders implement innovations, such as
      distance learning on-line, they must address the organization's political
      challenges and cultural changes. When leaders seek to introduce innovation within
      their organizations, they must be prepared for excitement as well as anxiety and
      resistance. Leadership also requires evaluating performance and outcomes for
      quality education. In addition, they strive to meet expectations of quality of
      all stakeholders. J Prof Nurs 17:166-172, 2001.

PMID- 11464338
TI  - Contractual issues for faculty practice.
AB  - Contracts are a common foundation for faculty practice relationships between a
      college of nursing and other agencies. Although the legal format of a contract is
      relatively standardized, the process of contracting entails decisions and issues
      that increase its complexity. Little is available in the faculty practice
      literature that addresses contracts and contractual issues as a comprehensive
      whole. This article contains discussions of nursing faculty practice contractual
      issues such as the elements of a contract as a framework, including competent
      parties, offer, consideration, and acceptance. Evaluation of contract performance
      is addressed and alternatives for decision making and problem resolutions are
      suggested throughout. J Prof Nurs 17:173-179, 2001.

PMID- 11464339
TI  - The faculty portfolio: documenting the scholarship of teaching.
AB  - The scholarship of teaching is considered an essential component of scholarship
      within academic settings. To promote the transfer of knowledge specific to the
      discipline of nursing, this category of scholarship must include inquiry into the
      practice of teaching, program development, and professional role modeling, in
      addition to excellence in teaching itself. Conveying what constitutes teaching
      scholarship in nursing may present special challenges for nurse faculty in the
      university setting. A faculty teaching portfolio is one mechanism for
      explicating, communicating, and enhancing the scholarship of teaching. The
      methodology for creating, improving, and maintaining a teaching portfolio
      includes analyzing the mission of the university, articulating a philosophy of
      teaching, deciding on goals and objectives, designing evaluative mechanisms,
      processing data, conducting a self-evaluation, applying new approaches, and
      revisiting and reflecting on the outcomes. Faculty teaching portfolios serve to
      display, communicate, and document the scholarship of teaching. The creative
      endeavors surrounding portfolio development are ongoing and recursive,
      necessitating self-reflection and new approaches. J Prof Nurs 17:180-186, 2001.

PMID- 11464340
TI  - Use of the Internet in survey research.
AB  - An Internet survey of the Pick's Disease Network showed the potential for use of
      the Internet for research into diseases that are too rare to find sufficient
      subjects to gather data on patient and family experiences, helpful interventions,
      and other care-related information. This descriptive survey used an author
      constructed instrument posted on a university server to collect information on
      both the affected persons and the family. Although the sample cannot be
      scientific and controlled, there was a 68.6 per cent response rate. The fact that
      specialists and imaging technology had been used in making the diagnoses, and
      that, with one exception, the responses were comparable to information in other
      reports, increased, confidence in the validity of the sample and the responses.
      One of the biggest needs of caregivers and family members was for more
      information and support. This survey indicates that such research can provide
      information about rare diseases so that nurses can be more helpful to patients
      and caregivers. Further exploration of research uses of the Internet could not
      only help to get information on rare diseases, but perhaps offer unique research
      opportunities to students who are using distance-education technologies. J Prof
      Nurs 17:187-193, 2001.

PMID- 11464341
TI  - Seeing the glass half full: living with Sjogren's Syndrome.
AB  - The purpose of this qualitative research was to explore the lived experiences of
      women with Sjogren's Syndrome (SS), a chronic autoimmune syndrome in which
      invading lymphocytes attack moisture-producing glands of the body. This syndrome,
      affecting 4 million Americans, involves extreme dryness of the eyes and mouth and
      other systemic complications such as fatigue and muscle and joint pain. Ten
      women, ranging in age from 27 to 83, with SS were interviewed to understand their
      coping strategies and attitudes. This study used Strauss' framework to view the
      quality of life of the chronically ill-specifically, those with SS. Nine
      questions were asked to elicit information on limitations with daily living,
      relationships, emotions about lifestyle changes, and comparisons with others
      living with chronic disease. In addition to SS, 8 of the 10 women also had
      fibromyalgia, and 4 had other conditions such as lupus and rheumatoid arthritis
      (secondary Sjogren's). Their responses were categorized into four groups:
      helping, hindering, hoping, and hurting. This led to the development of the 4H
      Model of Chronic Autoimmune Disease with subcategories such as: supporting,
      joining, comparing, coping, health promoting, fearing, becoming a chronic
      sufferer, feeling, wishing, appearing, impeding, restricting, isolating,
      suffering, doctoring, and diagnosing. J Prof Nurs 17:194-202, 2001.

PMID- 11464342
TI  - Professionalism in nursing behaviors of nurse practitioners.
AB  - Little research on the level of professionalism of nurse practitioners has been
      published to date. These nurses are expected to practice relatively autonomously
      in delivering client care and therefore must monitor their own levels of
      professionalism. At a national conference, 502 nurse practitioners completed the
      Professionalism in Nursing Behaviors Inventory. Participants represented all of
      the states and the most common specialties of nurse practitioners. Nearly 68 per
      cent had been practitioners less than 5 years and were primarily employed in
      physicians' offices. The majority had received their master's degrees from
      schools with nurse practitioner curricula, and 8 per cent held doctorates. More
      than one half of the practitioners had written a research proposal or
      participated in a project within the past 2 years. In terms of autonomy, nearly
      50 per cent of the nurses had written their own job descriptions. Maintaining
      certification motivated them to engage in some professionalism behaviors. Results
      indicated these nurse practitioners had high levels of professionalism. J Prof
      Nurs 17:203-210, 2001.

PMID- 11464343
TI  - Postdural puncture headache: mechanisms, treatment, and prevention.

PMID- 11464344
TI  - Lipid soluble opioids do move in cerebrospinal fluid.

PMID- 11464345
TI  - Multimodal therapy for post-cesarean delivery pain.

PMID- 11464346
TI  - The injection of intrathecal normal saline reduces the severity of postdural
      puncture headache.
AB  - BACKGROUND AND OBJECTIVES: We investigated whether the injection of 10 mL of
      normal saline into the subarachnoid space following accidental dural puncture
      reduced the incidence of postdural puncture headache (PDPH) and the need for
      epidural blood patch (EBP). METHODS: Twenty-eight patients who experienced
      accidental dural puncture with an epidural needle had 10 mL of normal saline
      injected into the subarachnoid space. In 22 patients, the injection was performed
      immediately through the epidural needle. In 6 patients who had intrathecal
      catheters placed through the epidural needle, the saline was injected through the
      catheter before removal. All other patients who experienced wet taps during the
      same period that the study was in progress but did not receive the saline
      injection served as a control group, 26 in number. Patients with severe or
      persistent PDPHs were treated with EBP. RESULTS: Of those patients who received
      intrathecal normal saline immediately through the epidural needle, 32% developed
      a headache compared with 62% of controls. Of these, 1 patient who received saline
      required EBP compared with nine in the control group (P =.004). Of those patients
      who had intrathecal catheters placed, there were no headaches in the saline group
      of 6 compared with 3 in the control group of 5, 1 of whom was treated with EBP (P
      >.05). CONCLUSIONS: The immediate injection of 10 mL intrathecal normal saline
      after a wet tap significantly reduced the incidence of PDPH and the need for EBP.
      When an intrathecal catheter had been placed following a wet tap, injection of 10
      mL of normal saline before its removal effectively prevented PDPH.

PMID- 11464347
TI  - The effect of distance from injection site to the brainstem using spinal
      sufentanil.
AB  - BACKGROUND AND OBJECTIVES: Intrathecal (IT) sufentanil is commonly used in
      parturients to provide rapid onset of labor analgesia without motor block. This
      practice, although widely used, has been associated with severe respiratory
      depression in some patients. The mechanism of this respiratory depression is
      unclear, however, rapid cephalad movement and interaction with parenteral opioids
      are 2 frequently cited explanations for this complication. Because this
      complication has occurred only in women with heights between 150 and 157 cm, we
      elected to study the effect of the distance from injection site to the cisterna
      magna (CM) on peak brainstem cerebrospinal fluid (CSF) concentrations. METHODS:
      Ten adult ewes were injected with IT sufentanil (0.3 microg/kg) at a mean
      distance of either 71 cm (65 to 78 cm) from the brainstem (pelvic group) or 37 cm
      (34 to 42 cm) from the brainstem (thoracic group). CSF was then sampled at 5
      minute intervals from the CM. RESULTS: Measurable CM concentrations of sufentanil
      were noted in the brainstem at 20 and 25 minutes, respectively, for the thoracic
      and the pelvic groups. Peak sufentanil concentrations from the thoracic group
      were nearly 10-fold higher (0.553 +/- 0.43 ng/mL) compared with the pelvic group
      (0.064 +/- 0.002 ng/mL) when measured in the CM (P =.023). CONCLUSIONS: Our
      results suggest that sufentanil migrates relatively large distances in the IT
      space. Injection site (distance from the brainstem) appears to be a prominent
      factor in determining brainstem concentrations and subsequent respiratory
      depression after spinal administration. Reg Anesth Pain Med 2001;26:306-309.

PMID- 11464348
TI  - Diclofenac and/or propacetamol for postoperative pain management after cesarean
      delivery in patients receiving patient controlled analgesia morphine.
AB  - BACKGROUND AND OBJECTIVES: A multimodal approach to postcesarean pain management
      may enhance analgesia and reduce side effects after surgery. This study evaluates
      the postoperative analgesic effects of propacetamol and/or diclofenac in
      parturients undergoing elective cesarean delivery under spinal anesthesia.
      METHODS: After randomization, 80 healthy parturients received the following:
      placebo (group M), 100 mg diclofenac rectally every 8 hours (group MD), 2 g
      propacetamol intravenously every 6 hours (group MP), or a combination of 2 g
      propacetamol and 100 mg diclofenac (group MDP) as described above. Drugs were
      administered for 24 hours after surgery. Postoperative pain was controlled with a
      patient controlled analgesia pump, using morphine. The visual analog scale (VAS)
      at rest and on coughing, as well as the morphine consumption, were evaluated at
      2, 6, and 24 hours postoperatively. Also, the side effects experienced after
      undergoing the different regimens were compared. RESULTS: The patients'
      characteristics did not differ significantly between the 4 groups. VAS score at 2
      hours, both at rest and on coughing were lower in group MDP and MD compared with
      group M (P <.05). At 24 hours, there was still a tendency toward lower pain
      scores in the groups MDP and MD; however, this difference was only statistically
      significant at rest between the MDP group and the MP and M groups. Morphine
      consumption at 2, 6, and 24 hours was lower in the MDP and MD groups compared
      with the MP and M groups (P <.05). The morphine-sparing effect was higher in
      groups MDP and MD compared with group MP (57% and 46%, respectively, v 8.2%, P
      <.05). The incidence of side effects was similar in all groups. However, the
      power of the study was too low to permit an evaluation of potential side effects.
      CONCLUSION: Diclofenac after cesarean delivery improves analgesia and has a
      highly significant morphine-sparing effect. We were unable to demonstrate
      significant morphine-sparing effect of propacetamol or additive effect of
      propacetamol and diclofenac in this group of patients.

PMID- 11464349
TI  - Randomized prospective study comparing preoperative epidural and intraoperative
      perineural analgesia for the prevention of postoperative stump and phantom limb
      pain following major amputation.
AB  - BACKGROUND AND OBJECTIVES: Acute stump pain and phantom limb pain after
      amputation is a significant problem among amputees with a reported incidence of
      phantom limb pain in the first year following amputation as high as 70%. Epidural
      analgesia before limb amputation is commonly used to reduce postamputation acute
      stump pain in the immediate postoperative period and phantom pain in the first
      year. We investigated whether immediate postamputation stump pain and phantom
      pain in the first year is reduced by preoperative epidural block with bupivacaine
      and diamorphine compared with intraoperative placement of a perineural catheter
      infusing bupivacaine. METHODS: In a randomized prospective trial, 30 patients
      scheduled for lower limb amputation were randomly assigned epidural bupivacaine
      at the standard rate used in our hospital (0.166%, 2 to 8 mL/h) and diamorphine
      (0.2 to 0.8 mg/h) for 24 hours before and during operation (14 patients; epidural
      group) and 3 days postoperatively, or an intraoperatively placed perineural
      catheter (16 patients; perineural group) for intra and postoperative
      administration of bupivacaine (0.25%, 10 mL/h). All patients had general
      anesthesia for the amputation and were asked about stump and phantom pain in the
      first 3 days and then at 6 and 12 months by an independent examiner. Study
      endpoints were rate of stump and phantom pain, intensity of stump and phantom
      pain, and consumption of opioids. The groups were well matched in baseline
      characteristics. RESULTS: Stump pain scores in the first 3 days were
      significantly higher in the perineural group compared with the epidural group (P
      <.01). After 3 days, 4 (29%) patients in the epidural group and 7 (44%) in the
      perineural group had phantom pain (P =.32). Numbers of patients with phantom pain
      for epidural versus perineural group were: 5 (63%) versus 7 (88%) (P =.25) at 6
      months; 3 (38%) versus 4 (50%) (P =.61) at 12 months. Stump pain and phantom
      sensation were similar in both groups at 6 and 12 months. CONCLUSIONS: Using our
      regimen, perioperative epidural block started 24 hours before the amputation is
      not superior to infusion of local anaesthetic via a perineural catheter in
      preventing phantom pain, but gives better relief of stump pain in the immediate
      postoperative period.

PMID- 11464350
TI  - Effects of gabapentin in acute inflammatory pain in humans.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study was to examine the analgesic
      effects of the anticonvulsant, gabapentin, in a validated model of acute
      inflammatory pain. METHODS: Twenty-two volunteers were investigated in a double
      blind, randomized, placebo-controlled cross-over study. Gabapentin 1,200 mg or
      placebo was given on 2 separate study days. Three hours after drug
      administration, a first-degree burn injury was produced on the medial aspect of
      the nondominant calf (12.5 cm(2), 47 degrees C for 7 minutes). Quantitative
      sensory testing (QST) included pain ratings to thermal and mechanical stimuli
      (visual analog scale [VAS]), assessments of thermal and mechanical detection
      thresholds, and areas of secondary hyperalgesia. Side effects drowsiness and
      postural instability were assessed by subjective ratings (VAS). RESULTS: The burn
      injury induced significant primary and secondary hyperalgesia (P <.0001).
      Gabapentin diminished the decrease in mechanical pain threshold in the burn area
      (P =.04) and reduced secondary hyperalgesia, but the reduction was not
      significant (P =.06). Heat pain thresholds, pain during the burn, and mechanical
      pain in the area of secondary hyperalgesia were not significantly changed by
      gabapentin (P <.2). Ratings of drowsiness and unsteadiness during walking were
      significantly higher for gabapentin than for placebo (P <.05). CONCLUSIONS: The
      study indicates that gabapentin has no analgesic effect in normal skin, but may
      reduce primary mechanical allodynia in acute inflammation following a thermal
      injury. These observations suggest a clinical potential of gabapentin in the
      treatment of postoperative pain.

PMID- 11464351
TI  - Addition of clonidine increases duration and magnitude of vasodilative effect
      induced by sympathetic block with mepivacaine in dogs.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study is to examine the duration and
      magnitude of vasodilative effect induced by sympathetic block with the addition
      of clonidine to mepivacaine. METHODS: We measured mean arterial pressure (MAP),
      heart rate (HR), and right and left brachial artery blood flow (BABF) before and
      after stellate ganglion block (SGB) in dogs. The experimental protocol was
      designed as follows: (1) left SGB using 1.0 mL 0.5% mepivacaine (n = 6) and (2)
      left SGB using the addition of clonidine 0.5 microg to 1.0 mL 0.5% mepivacaine (n
      = 6). RESULTS: MAP and HR did not change significantly throughout the study in
      either group. Left SGB with mepivacaine increased left BABF significantly from 10
      minutes through 50 minutes after SGB (baseline, 100%; peak at 10 minutes after
      SGB, 176% +/- 28%; P <.01). Left SGB with the addition of clonidine to
      mepivacaine induced a significant increase of left BABF from 10 minutes through
      70 minutes after SGB (baseline, 100%; peak at 10 minutes after SGB, 223% +/- 42%;
      P <.01). The values of left BABF after SGB with the addition of clonidine to
      mepivacaine were significantly higher than those of SGB with mepivacaine alone
      from 10 minutes through 80 minutes after SGB (P <.05). Right BABF decreased
      significantly after SGB throughout the study in both groups. CONCLUSIONS: The
      addition of clonidine increases both duration and magnitude of the vasodilative
      effect induced by sympathetic block over that caused by mepivacaine alone.

PMID- 11464352
TI  - Water-diluted local anesthetic for trigger-point injection in chronic myofascial
      pain syndrome: evaluation of types of local anesthetic and concentrations in
      water.
AB  - BACKGROUND AND OBJECTIVES: We have recently demonstrated that a mixture of 1%
      lidocaine with water in a 1:3 ratio has less injection pain and is more effective
      than unaltered 1% lidocaine in treating chronic myofascial pain syndromes. Yet,
      the most suitable local anesthetic and the most effective dilution in water have
      not been evaluated. METHODS: Various mixtures of local anesthetics and water or
      saline were injected intramuscularly into the shoulder of 40 female volunteers,
      and pain scores on injection were evaluated in a randomized and double-blinded
      manner. In another portion of the study, 0.25% or 0.2% lidocaine in water were
      injected randomly into 1 side of 21 outpatients with chronic neck, shoulder, or
      lumbar myofascial pain to the same degree in both sides. The other solution was
      injected into the other side of the same patients. RESULTS: Less injection pain
      was experienced with the water-diluted 0.25% lidocaine and water-diluted 0.25%
      mepivacaine than the saline-diluted 0.25% lidocaine and water-diluted 0.0625%
      bupivacaine. Also, less injection pain was experienced with the water-diluted
      0.25% and 0.2% lidocaine than the water-diluted 0.3% and 0.15% lidocaine. In the
      other study, there were no differences in either the effectiveness or duration of
      analgesia between the 0.25% and 0.2% water-diluted lidocaine. CONCLUSIONS: The
      suitable type of local anesthetic may be lidocaine or mepivacaine, and the most
      effective water-diluted concentration is considered to be 0.2% to 0.25%.

PMID- 11464353
TI  - Confirmation of location of epidural catheters by epidural pressure waveform and
      computed tomography cathetergram.
AB  - OBJECTIVE: Epidural pressure has remained a relatively unused test of
      physiological monitoring for the past 3 decades. It is our hypothesis that
      epidural pressure waveforms (EPWFs) obtained by transducing an epidural catheter
      (EC) can be used as a surrogate for the accurate location of the EC. The goal of
      this study was to validate this new method by comparing it with a more objective
      radiographic technique such as computed tomography cathetergram (CTC). METHODS:
      The EPWF and CTC were studied in 13 patients receiving continuous epidural
      analgesia (12 patients who had postoperative pain and 1 patient who had chronic
      pain). Of these 13 patients, 8 patients had reported inadequate analgesia, and 5
      had reported satisfactory analgesia. First, the end of the EC was connected to a
      disposable pressure transducer, this was followed by a 5-mL normal saline bolus
      injection to ensure the patency of the EC, and the EPWF was recorded. Next, the
      patient was taken to an imaging suite and, after injecting contrast through the
      EC, the course of the catheter was imaged with computed tomography (CT). The CT
      images were studied by the neuroradiologist and correlated with the EPWF.
      RESULTS: The EPWF of 5 patients with clinically adequate analgesia revealed a
      pulsatile waveform on transducing the EC and a crescentic spread of contrast in
      the epidural space on CTC. In 8 patients with inadequate epidural analgesia, the
      EPWF measurement failed to show oscillations, and contrast collections were
      observed in the paraspinous muscles. The results of EPWF and CTC were compared
      using Fisher's exact test. CONCLUSIONS: The strong relationship between EPWF and
      CTC suggests that EPWF can be used reliably to confirm the correct placement of
      the EC in a selected group of patients.

PMID- 11464354
TI  - Postoperative analgesia by intraarticular clonidine and neostigmine in patients
      undergoing knee arthroscopy.
AB  - BACKGROUND AND OBJECTIVE: Clonidine and neostigmine have a central mechanism of
      analgesic action and are synergistic when given intrathecally. Both drugs also
      have a peripheral analgesic effect. The purpose of this study was to compare the
      analgesic effect of intraarticular clonidine and neostigmine, used separately and
      in combination, in patients undergoing knee arthroscopy. METHODS: Eighty-four
      American Society of Anesthesiologists (ASA) I and II patients scheduled for
      meniscus repair under arthroscopy were allocated randomly in 6 groups to receive
      in a double-blind manner at the end of surgery 150 microg of intraarticular
      clonidine with subcutaneous saline, 500 microg of intraarticular neostigmine with
      subcutaneous saline, an intraarticular combination of 150 microg of clonidine and
      500 microg of neostigmine with subcutaneous saline, 150 microg of intraarticular
      clonidine with 500 microg of subcutaneous neostigmine, 500 microg of
      intraarticular neostigmine with 150 microg of subcutaneous clonidine, or
      intraarticular and subcutaneous isotonic saline. Postoperative pain scores were
      measured on a visual analog scale (VAS) at rest and on mobilization. Paracetamol
      (1 g) was given as a rescue medication when pain score was greater than 40.
      RESULTS: VAS scores at rest and on mobilization were lower in the first 5 groups
      compared with the intraarticular saline group (P <.05), but no significant
      difference was documented between the treated groups. The time to the first
      paracetamol administration was shorter in the saline group compared with the
      other groups, and the paracetamol demand was also higher in this group. Forty
      five percent of the patients who had received clonidine had at least 1 episode of
      hypotension versus 4% of those who did not (P <.01). The incidence of bradycardia
      was 20% and 0%, respectively (P =.01). The incidence of nausea was not
      statistically different in patients who did and did not receive neostigmine (43%
      v. 36%, respectively). CONCLUSION: Intraarticular administration of 150 microg of
      clonidine, 500 microg of neostigmine, or both produce postoperative analgesia,
      and the combination is not more effective.

PMID- 11464355
TI  - Clinical usefulness, safety, and plasma concentration of ropivacaine 0.5% for
      inguinal hernia repair in regional anesthesia.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the
      pharmacokinetics, feasibility, and clinical effects of ropivacaine in regional
      anesthesia (ilioinguinal-iliohypogastric blocks [IIB], genitofemoral block plus
      local infiltration) for inguinal hernia repair. METHODS: Following ethics
      committee approval and informed consent, 21 male adults received 60 mL
      ropivacaine 0.5% (without vasoconstrictor). In 11 patients, further injections of
      5 to 10 mL were given while preparing the hernial sack. Plasma concentration of
      ropivacaine was determined in venous blood after 10, 20, 30, 45, 60, 90, 120, and
      300 minutes using reversed-phase high pressure liquid chromatography (HPLC).
      RESULTS: Peak plasma concentrations of ropivacaine were 1.5 +/- 0.6 (0.7 to 2.6)
      microg/mL (mean +/- SD [range]). These maximum concentrations occurred after 45
      (30 to 60) minutes (median [range]). No signs of central nervous or
      cardiovascular toxicity were observed. Twelve of 21 patients did not need any
      additional analgesics within 24 hours postoperatively. One patient had a femoral
      motor block lasting 6 hours, 5 patients reported sensory femoral block lasting 5
      to 12 hours. Patients, as well as the surgeon, were very satisfied with the
      procedure, and all patients stated that they would like to have it performed
      again that way in case of an inguinal hernia on the opposite side. CONCLUSION: A
      ropivacaine dose of 60 to 70 mL of 0.5% appears adequate for regional anesthesia
      for inguinal hernia repair regarding conditions for surgery, safety, ambulation,
      and postoperative pain relief.

PMID- 11464356
TI  - Buprenorphine added to the local anesthetic for brachial plexus block to provide
      postoperative analgesia in outpatients.
AB  - BACKGROUND AND OBJECTIVES: Over the past 10 years, several studies have suggested
      that the addition of certain opiates to the local anesthetic used for brachial
      block may provide effective, long-lasting postoperative analgesia. One of these
      studies indicated that the agonist-antagonist, buprenorphine, added to
      bupivacaine provided a longer period of postoperative analgesia than the
      traditional opiates, but in this study, it is impossible to determine the
      relative contributions of the local anesthetic and the opiate to the
      postoperative analgesia because of the extremely long duration of the anesthesia
      provided by the local anesthetic, bupivacaine. By repeating the study using a
      local anesthetic of a shorter duration, the present study delineates more clearly
      the contribution of the buprenorphine to postoperative analgesia when added to a
      shorter-acting local anesthetic. METHODS: Forty, healthy, consenting adult
      patients scheduled for upper extremity surgery were enrolled in the study.
      Premedication was provided by intravenous midazolam 2 mg/70 kg and anesthesia by
      a subclavian perivascular brachial plexus block. The patients were assigned
      randomly to 1 of 2 equal groups based on the agents used for the blocks. The
      patients in group I received 40 mL of a local anesthetic alone, while those in
      group II received the same local anesthetic plus buprenorphine 0.3 mg. The study
      was kept double-blind by having 1 anesthesiologist prepare the solutions, a
      second anesthesiologist perform the blocks, and a third anesthesiologist monitor
      the anesthesia and analgesia thereafter, up to and including the time of the
      first request for an analgesic medication. The data were reported as means (+/-
      SEM), and differences between groups were determined using repeated measures of
      analysis of variance (ANOVA) and chi(2), followed by the Fisher exact test for
      post hoc comparison. A P value of less than.05 was considered to be statistically
      significant. RESULTS: The mean duration of postoperative pain relief following
      the injection of the local anesthetic alone was 5.3 (+/- 0.15) hours as compared
      with 17.4 (+/- 1.26) hours when buprenorphine was added, a difference that was
      statistically (and clinically) significant (P <.0001). CONCLUSIONS: The addition
      of buprenorphine to the local anesthetic used for brachial plexus block in the
      present study provided a 3-fold increase in the duration of postoperative
      analgesia, with complete analgesia persisting 30 hours beyond the duration
      provided by the local anesthetic alone in 75% of the patients. This practice can
      be of particular benefit to patients undergoing ambulatory upper extremity
      surgery by providing prolonged analgesia after discharge from the hospital.

PMID- 11464357
TI  - Does alkalinization of 0.75% ropivacaine promote a lumbar peridural block of
      higher quality?
AB  - BACKGROUND AND OBJECTIVES: We did not find clinical studies of the alkalization
      of ropivacaine in the literature. The objectives of this study were: (1) to
      determine the quantity of sodium bicarbonate (NaHCO(3)), which alkalinizes 0.75%
      ropivacaine (with and without adrenaline); (2) to verify the physico-chemical
      alterations arising from this alkalization; and (3) to determine whether
      alkalinized ropivacaine produces a higher-quality epidural block measured via
      sensory-motor onset, block spread and anesthesia duration. METHODS: It was
      determined in the laboratory that 0.012 and 0.015 mEq of NaHCO(3), respectively,
      alkalinized 10 mL of the 0.75% ropivacaine solutions without and with adrenaline
      (1:200,000). In the second phase, the study was random and double-blind and
      involved 60 patients divided into 3 groups of 20 (G1, G2, and G3). Via epidural
      lumbar blocks, these groups received, respectively, 10 mL of 0.75% ropivacaine
      plus 0.5 mL of 0.9% NaCl (solution A), 10 mL of 0.75% ropivacaine plus 0.0012 mEq
      of NaHCO(3) (solution B), and 10 mL of 0.75% ropivacaine (with adrenaline) plus
      0.015 mEq of NaHCO(3) (solution C). The pH, PCO(2) (partial CO(2) pressure), and
      the nonionized fractions of the 0.75% ropivacaine solutions were compared before
      and after the addition of 0.9% NaCl or NaHCO(3) or adrenaline plus NaHCO(3). The
      motor and sensory onsets, block spread, and the duration of the block were
      evaluated. RESULTS: The values of the pH, PCO(2), and nonionized fractions
      increased significantly in solutions B and C in relation to solution A. No
      differences among the groups were observed in relation to block spread and
      sensory-motor onset. The duration of the sensory blocks was significantly greater
      in the patients in groups G2 and G3. CONCLUSION: This study indicates that the
      quantity of NaHCO(3) needed to alkalize 10 mL of 0.75% ropivacaine at room
      temperature is 0.012 mEq. When the solution contains adrenaline 1:200,000 (mg.mL(
      1)), up to 0.015 mEq of NaHCO(3) may be added. The alkalization of the 0.75%
      ropivacaine solution did not cause a reduction of sensory-motor onset, but did
      provide a significant increase in the duration of the epidural block with no
      significant differences between the solutions with and without adrenaline.

PMID- 11464358
TI  - Cerebrospinal fluid leak treated by aspiration and epidural blood patch under
      computed tomography guidance.
AB  - BACKGROUND AND OBJECTIVES: Cerebrospinal fluid (CSF) leakage secondary to surgery
      of the spine is usually treated by drainage of CSF through a subarachnoid
      catheter or surgical repair of the dural tear. We present 2 cases in which the
      pseudomeningocele was treated by aspiration of the leaked CSF and blood patch
      under computed tomography (CT) guidance. CASE REPORT: Two patients had headache
      after spine surgery. Physical examination showed a bulging accumulation of fluid
      at the laminectomy site. Aspiration of the fluid followed by injection of the
      patients' blood was performed aseptically under CT guidance. The patients had
      resolution of their headache, and follow-up showed no recurrence of the CSF leak.
      CONCLUSIONS: CSF leak secondary to a surgical tear of the dura can be
      successfully treated by aspiration of the fluid followed by injection of the
      patient's blood. CT guidance is recommended to assess the extent of the CSF
      leakage, determine the degree of evacuation of the leaked CSF, and to confirm the
      injection of the blood into the epidural space and the space created by the
      pseudomeningocele.

PMID- 11464359
TI  - From neuralgia to peripheral neuropathic pain: evolution of a concept.

PMID- 11464360
TI  - Gabapentin for the treatment and prophylaxis of cluster headache.
AB  - BACKGROUND AND OBJECTIVES: Cluster headache is an uncommon debilitating condition
      for which effective management remains a challenge. We describe the use of
      gabapentin in the treatment and prophylaxis of cluster headache in a patient who
      was refractory to other treatments. CASE REPORT: A 38-year-old man had a history
      of intermittent right-side headaches for 24 years, diagnosed as cluster headache.
      He received only partial relief from a range of conventional treatments. A trial
      with gabapentin 300 mg twice daily was tried and found to be effective in
      treatment and prophylaxis of his headaches. CONCLUSION: Gabapentin was effective
      in the treatment of a patient with cluster headache. Further investigation of
      gabapentin compared with conventional treatments and placebo is warranted.

PMID- 11464361
TI  - Repeated psoas compartment blocks for the management of long-standing hip pain.
AB  - BACKGROUND AND OBJECTIVES: The psoas compartment block is used to produce
      analgesia of the lumbar plexus mainly for hip and knee surgery. It has also been
      used for the management of a long-standing pain due to hip joint degeneration.
      CASE REPORT: A 55-year-old woman with severe left hip pain received repetitive
      psoas compartment blocks over 18 months. The blocks provided her with effective
      pain control. The quality and duration of the block was improved by the addition
      of opioid to the local anesthetic. CONCLUSION: We successfully performed repeated
      psoas compartment blocks with a local anesthetic and subsequently with added
      opioids, which produced substantial pain relief, especially after the addition of
      opioids.

PMID- 11464362
TI  - Use of computed tomography for mandibular nerve block in the treatment of
      trigeminal neuralgia.

PMID- 11464363
TI  - Simple formulas for preparing local anesthetic solutions for infusion.

PMID- 11464364
TI  - The use of air for the identification of the epidural space.

PMID- 11464365
TI  - Epidural hematoma in a parturient who developed disseminated intravascular
      coagulation after epidural anesthesia.

PMID- 11464366
TI  - Use of ultrasound to control depth of needle insertion.

PMID- 11464368
TI  - The futility of using sharp pinprick (or cold) to assess spinal or epidural
      anesthesia for cesarean delivery.

PMID- 11464370
TI  - Thermophilic aerobic treatment of a synthetic wastewater in a membrane-coupled
      bioreactor.
AB  - Synthetic wastewater containing alpha-lactose and gelatin was treated in a
      thermophilic membrane-coupled bioreactor (MBR). Thermophilic (>45 degrees C)
      treatment represents a potentially advantageous process for high-temperature as
      well as high-strength industrial wastewaters susceptible to reactor autoheating.
      Thermophilic systems, however, generally support a nonflocculating biomass that
      resists conventional methods of cell separation from the treated wastewater. MBRs
      were applied to thermophilic treatment systems because bacterial cells can be
      retained regardless of cell aggregation. Thermophilic aerobic MBRs were
      successfully operated at high levels of biocatalyst and produced a better
      effluent quality than analogous thermophilic bioreactors without cell recycle. At
      a hydraulic residence time (HRT) of 13.1 h, the chemical oxygen demand (COD) of
      the membrane eluate improved from 760 mg l(-1) (without cell recycle) to 160 mg
      l(-1) (with cell recycle). Bacterial community shifts were detected by denaturing
      gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR) -amplified
      16S rRNA gene fragments - 6 of 13 bands disappeared within 2 days of MBR
      operation. A concomitant 40-50% reduction in physiological indicators of cell
      reactivity (RNA:protein; ATP:protein) was also observed. The specific activity of
      beta-galactosidase and aminopeptidase, however, increased by 10-25%, indicating
      that there is a definite advantage to MBR operation at the highest biomass level
      possible. Nucleotide sequence analysis of 16S rDNA clones identified phylotypes
      from the low-G+C Gram-positive division and the beta- and gamma-subdivisions of
      Proteobacteria.

PMID- 11464371
TI  - [Changes in serum levels of C-reactive protein and the soluble adhesion
      molecules, sE-selectin and sICAM-1, after transdermal 17-beta estradiol
      replacement].
AB  - OBJECTIVE: Increases in serum concentrations of C-reactive protein (CRP) and
      soluble adhesion molecules sE-selectin and sICAM-1 are regarded as risk factors
      of atherosclerosis now. We aimed to analyse an effect of estrogen replacement
      therapy (ERT) by transdermal 17-beta estrogen on the variables. DESIGN: A
      clinical study. SETTING: Division of Gynaecology and Obstetrics, Hospital, Jicin
      and Department of Gynaecology and Obstetrics, 1st Faculty of Medicine, Charles
      University, Prague, Czech Republic. METHODS: Serum concentrations of CRP (by
      immunoturbidimetry) and sE-selectin and sICAM-1 (both by ELISA test) were
      examined in 19 women (median age 50.0 years) after hysterectomy with both side
      adnexectomy before and after 4 months of continuous transdermal substitution by
      17-beta estradiol (ERT) in 1.5 mg dose daily. Data were compared by paired t-test
      or by Wilcoxon test. P = 0.05, or below was taken as significant. RESULTS: Serum
      concentration of C-reactive protein was decreased in treated women after 4 months
      of ERT (before ERT 1.82 +/- 2.20 mg/l, after 4 months of ERT 0.28 +/- 0.55 mg/l;
      p = 0.006) as well as both soluble adhesion molecules: sE-selectin (before ERT
      45.13 +/- 17.3 micrograms/l, after 4 months of ERT 31.39 +/- 9.03 micrograms/l; p
      = 0.027) and sICAM-1 (before ERT 271.84 +/- 62.30 micrograms/l, after 4 months of
      ERT 242.86 +/- 62.32 micrograms/l; p = 0.026). CONCLUSION: Transdermal
      substitution with 17-beta estradiol may reduce one of risk factor of
      atherogenesis in treated women after hysterectomy with both side adnexectomy.

PMID- 11464372
TI  - [Surgical treatment of male infertility].
AB  - OBJECTIVE: In the Czech Republic in the treatment of male infertility the most up
      to-date technologies of assisted reproduction have also become the methods of
      choice: MESA--microsurgical epididymal sperm aspiration, TESE--testicular sperm
      extraction and ICSI--intracytoplasmic sperm injection. The objective of the
      present study was an attempt to find a reliable predictor of results of planned
      TESE as prediction of possible successful sperm extraction can prevent
      unnecessary ovarian stimulation. DESIGN: Retrospective analysis of a group of 202
      men operated in the authors centre on account of azoospermia--65 patients with
      obstructive azoospermia and 137 patients with testicular azoospermia. SETTING:
      Andromeda, Biolab, Iscare IVF, Prague. METHOD: The following parameters were
      evaluated: testicular volume, FSH serum level and histological finding and their
      values were compared with results of TESE. RESULTS: Elevated FSH levels and low
      testicular volume do not rule out a positive result of TESE. The most accurate
      predictor is histological examination. Elongated spermatids were found in the
      histological material in 59.3% of the examined cases which correlates
      significantly with the 60.2% TESE yield in the evaluated group. CONCLUSION: The
      material assembled on operation was divided into three parts. One serves
      preparation of the perIerative native preparation, the second one is dispatched
      for histological examination and the largest part is frozen. Simultaneous
      collection of oocytes and sperm cells is done only in selected cases. The
      histological finding of elongated spermatids indicates a positive finding of
      sperm during TESE with an accuracy of 91%. Assessment of the causes of
      azoospermia, evaluation of the state of spermatogenesis and treatment are thus
      implemented by a single operation.

PMID- 11464373
TI  - [Psychology of urinary incontinence. I. Comparison of women with urgent and
      stress incontinence before initiation of therapy].
AB  - OBJECTIVE OF STUDY: Comparison of psychological characteristics of untreated
      female patients with urgent and stress urinary incontinence. DESIGN: First stage
      of a perspective comparative study. SETTING: Gynaecological and Obstetric
      Department of the Municipal Hospital Neratovice, Urogynaecological out-patient
      dept. of the Institute for Mother and Child in Prague-Podoli, the
      Urogynaecological out-patient dept. of the Gynaecological and Obstetric Clinic of
      the First Medical Faculty Charles University and General Faculty Hospital Prague.
      METHODS: The study compares a group of 54 patients with stress incontinence and a
      group of 16 patients with urgent incontinence. Before the onset of therapy the
      patients were examined by a series of psychodiagnostic tests: MMPI/100 (Minnesota
      Multiphasic Personality Inventory, abridged version), STAI (State-Trait Anxiety
      Inventory), SCL-90 (Symptom Check List), Luscher's colour test, guided interview.
      For statistical evaluation the sign test and t-test were used. RESULTS: In the
      MMPI/100 and SCL-90 questionnaires a significant difference was found, i.e. a
      greater psychopathology in women with urgent incontinence (in both instances p <
      0.01). The two groups did not differ in any single scale. STAI and the interview
      did not reveal any significant differences with the exception of greater
      importance of sexual contact in women with urgent incontinence (p < 0.05).
      CONCLUSION: In the group of women with urgent incontinence a higher non-specific
      psychopathology was proved as compared with women with stress incontinence.

PMID- 11464374
TI  - [Does bedrest after embryo transfer cause a worse outcome in in vitro
      fertilization?].
AB  - OBJECTIVE: To evaluate the effect of bed rest following embryotransfer (ET) on
      the results of an in vitro fertilization (IVF) program. DESIGN: A prospective
      randomized study. SETTING: Gyn.-Obst. Department--Assisted Reproduction Centre,
      1st Medical Faculty of Charles University Prague and General Hospital, Prague.
      METHODS: After randomisation of patients on two groups (N--no bed rest, L--bed
      rest), embryo transfer (ET) was performed and all patients stand-up 20 minutes
      later. Group N went home, group L continued bed rest in the hospital overnight.
      We compared results of IVF in both groups. RESULTS: Both groups (N = 20 patients,
      L = 18 patients) were comparable in the age, number of previous IVF attempts,
      stimulation protocol, person performing ET, number of transferred embryos,
      percentage of ICSI, percentage of diagnosis "tubal infertility" and age of
      embryos in the day of ET. Results for group N (no bed rest) were in all
      parameters better than for group L: implantation rate (IR) (22.5% versus 14.5%),
      IR of high quality embryos (25.8% versus 16.7%), pregnancy rate (50% versus
      22.2%, p = 0.08), Take-home baby rate (40% versus 11%, p = 0.07). No of results
      reached clear statistical significance as the study was finished for ethical
      reasons (worse results of more difficult therapy in group L). CONCLUSION: The
      overnight bed rest in the hospital following ET did not ameliorate results of
      IVF. There is a strong tendency to negative effect of bed rest. Similar results
      may be found on other authors, but they did not extend the sense of their studies
      to the question of negative effects of the bed rest after ET, being satisfied
      with the result of "no worse results after no bed rest".

PMID- 11464375
TI  - [Laparoscopic sterilization using the Filshie clip--a prospective study of 180
      patients].
AB  - OBJECTIVE: In this prospective study from 1997-2000, authors have been analyzing
      preliminary results of 180 tubal sterilizations, which were performed by method
      of the laparoscopic application of Filshie clips. DESIGN: Prospective study.
      SETTING: Department of operative gynaecology and minimally invasive surgery,
      Hospital Na Homolce, Prague. METHODS: The procedures were performed in accordance
      with the still valid Public Notice of the Czech Republic Ministry of Health n.
      1/1972, section 5/1972. The mean age of the patients was 38.6 years, with each
      patient having 2.1 living children on average. During the intervention 42% of the
      patients either had IUD or were taking a hormonal contraceptive, while 29% of the
      patients had in their history a record of previous abdominal surgery. RESULTS:
      The average duration of the operation (from the incision to the closure) was 14
      min. There were no per- or postoperative complications and until the present we
      have no knowledge of failure. In the view of both the patient and the surgeon,
      this is the most acceptable procedure. CONCLUSION: In accordance with the British
      (RCOG) and the Canadian Gynecological Society conclusions and also on the basis
      of many randomized studies and recommendations from WHO, we conclude that the
      laparoscopic approach with the mechanical tubal occlusion by means of the clip is
      the first choice method. Our previous experience and meta-analytic studies of the
      literature, demonstrate that from all accessible clip methods, the Filshie clip
      method is the most suitable as it has the lowest failure rate, the least
      occurrences of extrauterine gravidity (in a case of failure). Most importantly it
      is a simple, quick and easily taught method. Another potentially significant
      factor is the highest rate of successful reversibility.

PMID- 11464376
TI  - [A safe site for transposition of ovaries in radical hysterectomy for cervical
      carcinoma].
AB  - OBJECTIVE: To know the influence of twilight by using the radiotherapeutical
      technique box on hormonal function of ovaries. The aim of transposition of
      ovaries by radical hysterectomy of the cervical cancer is to move the ovaries out
      of radiotherapeutical target volume, and thus to protect their hormonal function.
      SETTING: Institute for the Care of Mother and Child, Prague, Czech Republic.
      METHODS: Computer simulation of radiation isodoses of linear accelerator on the
      transferred pictures of CT and calculation on the total dose, and radiobiological
      equivalent outside the target volume of radiation regarding the total dose of 46
      Gy. RESULTS: In the pelvis region the minimal dose succeeded in acting as a
      castrating dose. The safe area is 2.5 cm above the margin of the radiation beam.
      CONCLUSION: It can be recommended to tuck the ovaries 3.5 cm above the margin of
      the pelvis.

PMID- 11464377
TI  - [Extraperitoneal cesarean section--an alternative or routine?].
AB  - OBJECTIVE: Evaluation of the importance of extraperitoneal Caesarean section in
      contemporary obstetrics. DESIGN: Review. SETTING: Gynaecological and Obstetrics
      Department, Bata Hospital Zlin. SUBJECT: A historical review of views on the
      approach to the lower uterine segment in Caesarean section and definition of some
      myths associated with extraperitoneal Caesarean sections. Retrospective analysis
      of the development of indications for this operation in 1977-1999 and their
      possible advantages. RESULTS: Analysis of 318 operations proved possible
      advantages of the operation during the perioperative period as well as during
      convalescence. CONCLUSION: Extraperitoneal Caesarean section can be considered an
      alternative of other surgical methods and procedures in infected cases and also
      an operation which can be implemented under all conditions except peracute
      states. The limiting factor is in particular the surgeon not familiar with the
      extraperitoneal technique. It is an operation with reduced invasiveness.

PMID- 11464378
TI  - [Recommendations for diagnosis and therapy of premenstrual syndrome].

PMID- 11464379
TI  - [Recommendations for prescription of intrauterine contraception].

PMID- 11464380
TI  - [Role of total laparoscopic hysterectomy in genital reconstruction in
      transsexuals].
AB  - OBJECTIVE: Evaluation of the suitability of total laparoscopic hysterectomy as an
      adjunctive procedure in the female-to-male transsexual reassignment surgery.
      Surgical reassignment surgery in the transsexual is not a frequent procedure. The
      expertise of an gynaecologist in the treatment of the syndrome is necessary as
      well as the input of other specialists such as psychiatrists, psychologists,
      plastic and reconstructive surgeons and urologists. The gynaecological surgeon
      usually performs the hysterectomy and in some cases also colpectomy. SUBJECT:
      Case report. METHODS: The authors analyse their own surgical experience with the
      above mentioned syndrom in the patient in whom the surgical reconstruction took
      place in two phases. In the first phase the Total Laparoscopic Hysterectomy with
      Bilateral Salpingo Ophorectomy (TLH, BSO) was performed. Of note is that this
      procedure was chosen due to extremely narrow vaginal canal with no uterine
      descent. For the second phase of the surgery the patient was referred to the
      urological surgeon. RESULTS: The duration of the surgery was 54 minutes, the
      blood loss was not measurable. We have not encountered any per- and postoperative
      complications and the patient was discharged after 48 hours. CONCLUSION: We
      conclude that the TLH/BSO approach has enabled to us to preserve the vital
      structures needed for reconstruction of external genitalia, e.g. inferior
      epigastric vessels and rectus muscles were not disturbed. This approach is
      complex and has clear advantages in comparison to vaginal hysterectomy,
      laparoscopic assisted vaginal hysterectomy or even total abdominal hysterectomy.
      It does guarantee a smooth removal of both ovaries and it is not dependent on the
      size of the vagina or uterine descent.

PMID- 11464381
TI  - [Laparoscopic therapy of symptomatic splenic implants in the minor pelvis].
AB  - OBJECTIVE: The radical laparoscopic treatment of the aforementioned pathology has
      made it possible to eliminate recurrent pelvic pain of the 24 years old patient.
      SUBJECT: Case report. METHODS AND RESULTS: 24 year old, nulligravid patient, had
      primary laparoscopy in 1998 because of chronic pelvic pain. Histology has
      confirmed both, the infiltrative endometriosis and the pelvic splenosis. While
      the endometriosis has been radically excised, splenic implants have been, in
      accordance with the current opinions in the literature, left in situ. Only their
      biopsy has been done. Due to recurrent pelvic pain after 15 months and the growth
      of the splenical implants, the second look laparoscopy was performed with the
      radical excision of these foci. CONCLUSION: The patient, 4 months after the
      intervention is asymptomatic. At variance with most of the literature, we assume
      that the pelvic splenosis in contrast to the abdominal is in many cases
      symptomatic. It causes especially pelvic pain and dyspareunia in connection with
      the contingent implant growth. In such cases the radical excision is indicated,
      where the laparoscopy is the chosen method. Authors are discussing the
      differentiational diagnosis of this syndrome especially concerning endometriosis,
      peritoneal carcinomatosis, accessory spleen and the manifestation of the
      lymphoma.

PMID- 11464382
TI  - [Importance of iodine intake during pregnancy--iodine supplementation and its
      risks].
AB  - Expressive deficiency of iodine (level of iodine in the urine is under 50
      micrograms/l) is characteristic for 10% children and 20% adult. Low levels of
      iodine in the urine were described by women after the delivery and by newborns.
      In the article are described specificity physiology of the thyroid gland,
      consequences of low intake of iodine, importance and risk of supplementation of
      iodine in the pregnancy. Intake of dose 200 micrograms iodine per day for
      pregnant women is important as the prevention of pathophysiological changes in
      the pregnancy and for development of foetus.

PMID- 11464383
TI  - [Contraception with depot gestagens].
AB  - OBJECTIVE: Summary of contraceptive implants and injectable contraceptives.
      DESIGN: Review of the literature. SETTING: Department of Gynaecology and
      Obstetrics, 1st Faculty of Medicine, Charles University, Prague. RESULTS:
      Contraceptive implants and injectable contraceptives are systems based on
      continuous release of small dose of progestogen in the circulation. Active
      substances are depo-medroxyprogesterone acetate in the Depo-Provera injections
      and levonogestrel in Norplant implants. Mechanisms of action are: inhibition of
      ovulation, impermeability of cervical mucus and synchronisation of maturation of
      endometrial stroma and glands. Efficacy of both of the methods is very high.
      Recovery of fertility is immediately in after Norplant removal and in few months
      after discontinuation of Depo-Provera. Progesterone only contraception has only
      very few contraindications which are only relative. It is possible to use her by
      the women with contraindications of combined oral contraception. The main side
      effect is altered menstrual bleeding pattern.

PMID- 11464384
TI  - [Conservative treatment of dysfunctional uterine bleeding].
AB  - OBJECTIVE OF STUDY: Analysis of contemporary knowledge of conservative treatment
      of dysfunctional bleeding. DESIGN: Review of literature. SETTING: Gynaecological
      and Obstetric Clinic, First Medical Faculty Charles University and General
      Faculty Hospital, Prague. METHOD: Evaluation and review of problem of DUB based
      on data from the literature. CONCLUSION: The development of new therapeutic
      surgical methods of uterine bleeding calls for a critical evaluation of a
      possible conservative approach. A few years ago failure of medicamentous
      treatment was an indication for hysterectomy. Thus conservative treatment was
      used very frequently. The development of many endoscopic techniques changed
      fundamentally the algorithm of treatment in women who do not plan another
      pregnancy. The article gives a critical account of contemporary knowledge of
      conservative treatment of dysfunctional uterine bleeding.

PMID- 11464385
TI  - [Cyclical changes in the ovaries and uterus in ultrasonic imaging].
AB  - OBJECTIVE OF STUDY: Summary of findings on possibilities of ultrasound
      examination of the uterus and ovaries. DESIGN: Review. SETTING: Gynaecological
      and Obstetric Clinic First Medical Faculty Charles University and General Faculty
      Hospital Prague 2, Apolinarska 18. MATERIAL AND METHODS: Processing of data in
      the literature on possibilities of gynaecological ultrasound examination.
      CONCLUSION: Ultrasound examination is an indispensable part in the diagnosis of
      pathological conditions of the uterus and ovaries.

PMID- 11464386
TI  - Workers' compensation latex claims.

PMID- 11464387
TI  - Workers' compensation claims from latex glove use.

PMID- 11464388
TI  - Meta-analysis of risk estimates for prostate cancer among rubber workers.

PMID- 11464389
TI  - Opportunities and challenges in leading a professional organization: a recent
      president's perspective.

PMID- 11464390
TI  - The incidence of green tobacco sickness among Latino farmworkers.
AB  - We estimated the prevalence and incidence density (ID) and the risk factors of
      green tobacco sickness among minority farmworkers in North Carolina. Using a
      prospective surveillance design, 182 farmworkers were interviewed up to 5 times
      at biweekly intervals in 1999. The green tobacco sickness prevalence was 24.2%,
      whereas the ID was 1.88 days per 100 days worked. Greater work experience (5+
      years, ID = 0.87; first year ID = 2.41) and tobacco use (ID of 1.18 vs 2.39) were
      negatively associated with green tobacco sickness. Task (e.g., priming ID, 4.04;
      topping ID, 1.86; barning ID, 0.62) and working in wet clothing (25% of workdays
      ID, 2.97; fewer than 25% of workdays ID, 1.29) had the largest effect. More
      effort must be directed toward preventing this occupational illness that affects
      workers who have little control over workplace safety.

PMID- 11464391
TI  - Pathological excretion patterns of urinary proteins in miners highly exposed to
      dinitrotoluene.
AB  - A cohort of 161 underground miners who had been highly exposed to dinitrotoluene
      (DNT) in the copper-mining industry of the former German Democratic Republic was
      reinvestigated for signs of subclinical renal damage. The study included a
      screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary
      proteins alpha 1-microglobulin and glutathione-S-transferase alpha (GST alpha) as
      biomarkers for damage of the proximal tubule and glutathione-S-transferase pi
      (GST pi) for damage of the distal tubule. The exposures were categorized
      semiquantitatively (low, medium, high, and very high), according to the type and
      duration of professional contact with DNT. A straight dose-dependence of
      pathological protein excretion patterns with the semiquantitative ranking of DNT
      exposure was seen. Most of the previously reported cancer cases of the urinary
      tract, especially those in the higher exposed groups, were confined to
      pathological urinary protein excretion patterns. The damage from DNT was directed
      toward the tubular system. In many cases, the appearance of Tamm-Horsfall
      protein, a 105-kD protein marker, was noted. Data on the biomarkers alpha 1
      microglobulin, GST alpha, and GST pi consistently demonstrated a dose-dependent
      increase in tubular damage, which confirmed the results of screening by SDS-PAGE
      and clearly indicated a nephrotoxic effect of DNT under the given conditions of
      exposure. Within the cluster of cancer patients observed among the DNT-exposed
      workers, only in exceptional cases were normal biomarker excretions found.

PMID- 11464392
TI  - The intervention research process in occupational safety and health: an overview
      from the National Occupational Research Agenda Intervention Effectiveness
      Research team.
AB  - The goal of occupational safety and health intervention effectiveness research is
      to determine whether specific interventions work to prevent work-related injury
      and illness. But that is not the whole story. It is also important that the
      development and implementation of the intervention be evaluated. All three phases
      (development, implementation, and effectiveness) are central to a model of
      intervention research proposed by the National Occupational Research Agenda
      Intervention Effectiveness Research team. Areas for future research are also
      presented.

PMID- 11464393
TI  - Pulmonary function in long-term asbestos workers in China.
AB  - The relationship of pulmonary function to exposure to asbestos and radiographic
      abnormalities has been controversial, especially when smoking is present as a
      confounder. The aim of the study was to provide further understanding on the
      radiographic-physiologic associations in nonsmoking and smoking asbestos workers.
      Radiographic asbestosis, pleural lesion, and pulmonary function were studied in
      269 Chinese asbestos workers, with average exposure years of 23 for male workers
      and 18 for female workers. Their functional data were compared with those of 274
      controls without exposure to dust. Although most of the male workers were
      smokers, none of the female workers smoked. In comparison with controls, asbestos
      workers had significantly lower lung volume and diffusing capacity, irrespective
      of gender. Female workers and smoking male workers had lower measurements of
      forced expiratory volume in 1 second and instantaneous forced expiratory flow at
      50% and 25% of forced vital capacity. After adjustment for relevant covariates,
      asbestos exposure, asbestosis, and pleural abnormalities were associated with
      decreased parameters of pulmonary function, including lung volume, diffusing
      capacity, and airway flow. These data indicate that asbestos-related functional
      defects manifested by lung restriction and mild airway obstruction correlate with
      exposure to asbestos and with parenchymal and pleural abnormalities, independent
      of smoking.

PMID- 11464394
TI  - Prevalence of thyroid diseases in Nevada counties with respect to perchlorate in
      drinking water.
AB  - Perchlorate is well-known to inhibit the uptake of iodine by the thyroid and has
      been shown to do so at doses in the milligrams-per-day range and higher.
      Perchlorate has been found in the water supply of Clark County (Las Vegas),
      Nevada, at 4 to 24 micrograms/L (parts per billion) and may provide exposure
      dosages in the tens of micrograms per day. An analysis of the Medicaid database
      from Nevada was undertaken to determine whether an increase in the prevalence of
      any thyroid disease was associated with that level of perchlorate content. The
      prevalence of persons being seen for thyroid disease or for specific thyroid
      diseases (goiter, nodule, thyrotoxicosis, congenital hypothyroidism, acquired
      hypothyroidism, thyroiditis, and other thyroid disorders) and for thyroid cancer
      among the Medicaid-eligible population of each county was calculated for the 2
      year period 1997 to 1998. The prevalences in Clark County were compared with
      those in Washoe County (i.e., Reno), the second most populous county in the
      state, and with those for the rest of the state. There was no evidence of an
      increased rate of thyroid disease (or of any specific thyroid disease) associated
      with perchlorate exposure. Generally, the prevalences in the metropolitan parts
      of the state were lower than for the rest of the state, particularly for acquired
      hypothyroidism. This analysis found no evidence that perchlorate-containing
      drinking water at the given level increased the prevalence of acquired
      hypothyroidism or of any other thyroid condition.

PMID- 11464395
TI  - Cancer mortality in relation to environmental chromium exposure.
AB  - From the 1950s to the 1980s, hexavalent chromium compounds were used as additives
      at certain water-cooling towers at three southern California gas compressor
      facilities. Claims of potential residential chromium exposure prompted the
      examination of age-adjusted mortality rates during 1989 to 1998 for lung cancer,
      all cancer, and all deaths for neighborhoods near versus distant from the plants.
      Differences in the rates between areas tended to be small and not statistically
      significant. The only significant difference was a lower, rather than higher,
      rate of total cancer among women in the potentially exposed areas. Study
      limitations preclude a definitive assessment of risk, but similar to previous
      investigations of cancer in relation to environmental chromium exposure in other
      locations, this study found no evidence of a cancer hazard among residents living
      near these California gas compressor facilities.

PMID- 11464396
TI  - Agricultural exposure to carbamate pesticides and risk of non-Hodgkin lymphoma.
AB  - Recent epidemiological studies have suggested an increased risk of non-Hodgkin
      lymphoma (NHL) from carbamate insecticide use among farmers. To further explore
      the possible relationships, we conducted a pooled analysis of three population
      based case-control studies conducted in four midwestern states in the United
      States. A total of 985 white male subjects and 2895 control subjects were
      included in this analysis. Unconditional logistic regression was used to estimate
      the association and control for confounding. Compared with nonfarmers, farmers
      who had ever used carbamate pesticides had a 30% to 50% increased risk of NHL,
      whereas farmers without carbamate pesticide use showed no increased risk.
      Analyses for individual carbamate pesticides found a more consistent association
      with Sevin but not carbofuran, butylate, or S-ethyl dipropylthiocarbamate plus
      protectant. Among farmers using Sevin, the risk of NHL was limited to those who
      personally handled the product, those who first used the product for > or = 20
      years before their disease diagnosis, and those who used the product for a longer
      period. These associations persisted after adjusting for other major classes of
      pesticides. These results suggest an increased risk of NHL associated with
      carbamate pesticide use, particularly Sevin. Further investigation of the
      association is warranted.

PMID- 11464397
TI  - Firefighters' hearing: a comparison with population databases from the
      International Standards Organization.
AB  - We investigated firefighters' hearing relative to general population data to
      adjust for age-expected hearing loss. For five groups of male firefighters with
      increasing mean ages, we compared their hearing thresholds at the 50th and 90th
      percentiles with normative and age- and sex-matched hearing data from the
      International Standards Organization (databases A and B). At the 50th percentile,
      from a mean age of 28 to a mean age of 53 years, relative to databases A and B,
      the firefighters lost an excess of 19 to 23 dB, 20 to 23 dB, and 16 to 19 dB at
      3000, 4000, and 6000 Hz, respectively. At the 90th percentile, from a mean age of
      28 to a mean age of 53 years, relative to databases A and B, the firefighters
      lost an excess of 12 to 20 dB, 38 to 44 dB, 41 to 45 dB, and 22 to 28 dB at 2000,
      3000, 4000, and 6000 Hz, respectively. The results are consistent with
      accelerated hearing loss in excess of age-expected loss among the firefighters,
      especially at or above the 90th percentile.

PMID- 11464398
TI  - Low job satisfaction predicts delayed return to work after laparoscopic
      cholecystectomy.
AB  - We studied 102 consecutive employed patients treated by elective laparoscopic
      cholecystectomy to determine job characteristics and psychological factors that
      predict delay in return to work after their procedure. Median sick leave was 13
      days, and five variables significantly added to a model predicting sick leave of
      at least 20 days (31.4% of the workers): low job satisfaction (odds ratio [OR],
      12.56; 95% confidence interval [CI], 3.34 to 47.2); physical effort at work (OR,
      4.99; 95% CI, 1.46 to 17.04); pain at 7 days (OR, 5.55; 95% CI, 1.56 to 19.76);
      patient's expectation of slow recovery (> 7 days) (OR, 6.12; 95% CI, 1.82 to
      20.55); and patient's expectation of no financial loss (OR, 3.85; 95% CI, 1.14 to
      12.50). The model was excellent (area under the receiver operating characteristic
      curve, 89.6%). We conclude that low job satisfaction is a major predictor of
      delayed return to work.

PMID- 11464399
TI  - The roles of the Army Medical Services--shaping the battlespace?

PMID- 11464400
TI  - Preparation for deployment abroad.

PMID- 11464401
TI  - Symptomatic approach to problems while working in the tropics.

PMID- 11464402
TI  - A practical approach to problems on return from deployment.

PMID- 11464403
TI  - The management of near drowning.

PMID- 11464404
TI  - Terrorism--new threats, new challenges?

PMID- 11464405
TI  - Fluid Resuscitation in Pre-Hospital Trauma Care: a consensus view.
AB  - Fluid administration for trauma in the pre-hospital environment is a challenging
      and controversial area. There is not yet any equivocal answer which can be
      supported by clear unanswerable evidence. Nevertheless, a careful reading of what
      evidence is available does allow some provisional conclusions to be drawn. We
      believe that the following represent the best possible current expert consensus
      on pre-hospital fluids in trauma. As future evidence brings clarity to this area,
      these guidelines can be modified, and further consensus statements will be issued
      taking into account such information. When treating trauma victims in the pre
      hospital arena: Cannulation should take place en route where possible Only two
      attempts at cannulation should be made Transfer should not be delayed by attempts
      to obtain intravenous access Entrapped patients require cannulation at the scene
      Normal saline is recommended as a suitable fluid for administration to trauma
      patients Boluses of 250 ml fluid may be titrated against the presence or absence
      of a radial pulse (caveats; penetrating torso injury, head injury, infants).

PMID- 11464406
TI  - Clinical findings of the second 1000 UK Gulf War veterans who attended the
      Ministry of Defence's Medical Assessment Programme.
AB  - OBJECTIVE: To review the diagnoses made in the second 1000 veterans of the Gulf
      conflict 1990-91 seen in the Ministry of Defence's Gulf Veterans' Medical
      Assessment Programme and to determine the main conditions related to Gulf
      service. DESIGN: Case series of 1000 consecutive Gulf veterans who presented to
      the programme between 25 February 1997 and 19 February 1998. SUBJECTS: Gulf War
      veterans. MAIN OUTCOME MEASURES: Assessment of the patient's health status.
      Diagnosis of medical and psychiatric conditions using ICD-10. RESULTS: 204
      patients were unwell. 309 patients had organic disease, of whom 248 were well,
      252 had psychiatric conditions which remained active in 173. The remaining 79,
      now well, had had psychiatric disorders following Gulf service. The principal
      psychiatric diagnosis was post traumatic stress disorder and the majority arose
      as a result of Gulf service. CONCLUSION: 796 (80%) veterans were well. There were
      309 (31%) patients with organic disease. 252 (25%) veterans had psychiatric
      conditions of which 173 (69%) had an active diagnosed disorder and post traumatic
      stress disorder was the predominant condition. The pattern of disease is similar
      to that seen in NHS practice. We found, like others, no evidence to support a
      unique Gulf War syndrome. Post conflict illnesses have many common features.

PMID- 11464407
TI  - Organisation and design of regular field hospitals.
AB  - The organisation and design of field hospitals within the British Army has been
      under review since the GulfWar. This paper discusses principles for the
      organisation and design of field hospitals and makes suggestions for further
      development. The paper describes the deployment of field hospitals from a 25 bed
      hospital troop up to a 200 bed field hospital.

PMID- 11464408
TI  - The military medical management of missile injury to the spine: a review of the
      literature and proposal of guidelines.
AB  - The management of missile injury to the spinal cord is controversial. The
      literature is reviewed and recommendations made about the management of these
      injuries. To surgeons in a country that is relatively safe such injuries are
      rare, this review provides useful information about this condition.

PMID- 11464409
TI  - Use of simulation technology in Australian Defence Force resuscitation training.
AB  - Realistic training of health personnel for the resuscitation of military
      casualties is problematic. There are few opportunities for personnel to obtain
      the necessary experience unless working in a busy emergency or trauma
      environment. Even so, the specific nature of military trauma means that many
      aspects of casualty management may not be adequately covered in the civilian
      domain. This paper discusses the use of advanced simulation technology in the
      training of military resuscitation teams. Such training has been available to
      members of the Australian Defence Force (ADF) for two years.

PMID- 11464410
TI  - Primary closure of battle wounds of the colon: is it an option for the military
      surgeon?
AB  - The management of battle wounds of the colon has been safely established for many
      years, with primary closure of the wounds being discouraged. More recent work,
      involving large numbers of patients from civilian trauma centres, has challenged
      this. The appropriateness of these conclusions for the battle situation is
      discussed, including the nature of injury, the medical logistics and the combat
      scenario. Parameters are indicated and guide lines given, incorporating battle
      proven military surgical principles and modern trauma experience. This includes
      damage control and possible primary closure of selected wounds. In this way the
      military surgeon can take an informed decision in providing optimal care for
      patients with battle wounds of the colon.

PMID- 11464411
TI  - The treatment role of the plastic nail guard for ingrowing toenails.
AB  - An illustrative case of bilateral ingrowing toe-nails highlights the practical
      advantages of the use of the plastic nail guard (PNG). Insertion of the PNG is
      inexpensive and is easy to learn and perform. The technique is described and
      discussed. Its recurrence rate compares favourably with simple avulsion and wedge
      resection.

PMID- 11464412
TI  - Battlefield advanced trauma life support (BATLS).

PMID- 11464413
TI  - Sierra Leone 1914.

PMID- 11464414
TI  - Ambroise Pare (1510-1590).

PMID- 11464415
TI  - The initial management of acute burns.
AB  - The initial management of burns, in common with all trauma, follows the ABCDE
      approach. The outline management plan detailed above assumes the availability of
      certain medical supplies but even simple measures are invaluable in burn care if
      they are all that are available. The most basic supplies required to resuscitate
      a casualty are oral salt and water in appropriate volumes. Similarly it should be
      possible in field conditions to monitor vital signs and urine output, dress the
      burns with clingfilm or plastic bags and wrap the casualty in absorbent
      materials.

PMID- 11464416
TI  - Self assessment exercises in cold weather remote medicine.

PMID- 11464417
TI  - Occupational Medicine & Army aviation medicine. The doctors who assess groups as
      well as individuals. The flying doctors.

PMID- 11464419
TI  - Preparing for the MRCP(UK) Part I examination.

PMID- 11464420
TI  - Write an original paper.

PMID- 11464421
TI  - Medical support on a Himalayan expedition.

PMID- 11464422
TI  - DNA identification.

PMID- 11464423
TI  - Thoughts on Kosovo.

PMID- 11464424
TI  - An early multi-tool.

PMID- 11464425
TI  - Decomposing pharmaceutical cost growth in different types of health plans.
AB  - OBJECTIVE: To decompose pharmaceutical spending growth into price and quantity
      components and to compare growth across different types of health plans. STUDY
      DESIGN: Retrospective analysis of pharmaceutical claims for active employees of a
      large national employer from 1996 to 1998, who were enrolled in traditional fee
      for-service plans, health maintenance organizations (HMOs), and preferred
      provider organizations. OUTCOME MEASURES: Outcomes measures included total cost
      growth, price growth, and quantity growth. Quantity growth was divided into
      growth in use of existing products and in use of newly introduced products. For
      existing products, quantity growth was further decomposed into growth in the
      number of prescriptions and change in the mix of prescriptions. RESULTS: During
      the study period, HMOs had the greatest cost growth. This differential cost
      growth was largely attributable to changes in utilization as opposed to changes
      in prices, which were similar among types of health plans. Introduction of new
      products contributed 15 to 20 percentage points to cost growth in each setting.
      Differences in cost growth were largely attributed to differences in the growth
      rate of spending on existing products. For existing products, the impact of
      increases in the number of prescriptions was much greater in the HMOs, while the
      impact of changes in the mix of prescriptions was only mildly greater in the
      HMOs. CONCLUSIONS: Pharmaceutical cost growth was largely attributable to changes
      in utilization as opposed to changes in prices. Changes in utilization patterns
      were complex and differed across types of health plans.

PMID- 11464426
TI  - Economic evaluation of lamivudine compared with interferon-alpha in the treatment
      of chronic hepatitis B in the United States.
AB  - OBJECTIVE: To determine whether lamivudine or interferon-alpha (IFN-alpha) is the
      more successful treatment for chronic hepatitis B given a fixed drug budget.
      STUDY DESIGN: A decision-tree model of 1 year. PATIENTS AND METHODS: Average
      wholesale prices were used to estimate drug costs. A fixed drug budget of
      $558,910, sufficient to treat 100 patients with IFN-alpha, was assumed. Clinical
      data were taken from randomized controlled trials. The outcome measures used were
      hepatitis B "e" antigen (HBeAg) seroconversion rates and rates of progression to
      cirrhosis. RESULTS: The analysis showed that given the fixed drug budget, 353
      patients could be treated with lamivudine, resulting in an expected 62 HBeAg
      seroconversions, with 6 patients progressing to cirrhosis. Given the same drug
      budget, 100 patients could be treated with IFN-alpha, leaving 253 patients
      untreated. This treatment scenario would result in an expected 32 HBeAg
      seroconversions, with 28 patients progressing to cirrhosis. Compared with no
      treatment, the costs per additional HBeAg seroconversion obtained were $12,703
      for lamivudine and $39,922 for IFN-alpha. In addition, each case of cirrhosis
      avoided through lamivudine treatment resulted in significant annual cost savings.
      Lamivudine therapy also provided additional clinical benefits (e.g.,
      normalization of alanine transaminase levels, reduction in hepatitis B virus DNA
      levels, improvement in liver histology) to patients who do not seroconvert.
      CONCLUSION: From the perspective of a third-party payer with a fixed drug budget,
      lamivudine is more cost-effective therapy than IFN-alpha for the treatment of
      chronic hepatitis B.

PMID- 11464427
TI  - Promoting smoking abstinence in pregnant and postpartum patients: a comparison of
      2 approaches.
AB  - OBJECTIVE: To compare the implementation, delivery, and implications for
      dissemination of 2 different maternal smoking-cessation/relapse-prevention
      interventions in managed care environments. STUDY DESIGN: Healthy Options for
      Pregnancy and Parenting (HOPP) was a randomized, controlled efficacy trial of an
      intervention that bypassed the clinical setting. Stop Tobacco for OuR Kids
      (STORK) was a quasi-experimental effectiveness study of a point-of-service
      intervention. Both incorporated prenatal and postnatal components. PATIENTS AND
      METHODS: Subjects in both studies were pregnant women who either smoked currently
      or had quit recently. The major intervention in HOPP was telephone counseling
      delivered by trained counselors, whereas the STORK intervention was delivered by
      providers and staff during prepartum, inpatient postpartum, and well-baby visits.
      RESULTS: In HOPP, 97% of telephone intervention participants reported receiving 1
      or more counselor calls. The intervention delayed but did not prevent postpartum
      relapse to smoking. Problems with intervention delivery related primarily to
      identification of the target population and acceptance of repeated calls. STORK
      delivered 1 or more cessation contacts to 91% of prenatal smokers in year 1, but
      the rate of intervention delivery declined in years 2 and 3. Modest differences
      were obtained in sustained abstinence between 6 and 12 months postpartum, but not
      in point prevalence abstinence at 12 months. CONCLUSIONS: The projects were
      compared using 4 of the 5 dimensions of the RE-AIM model including reach,
      adoption, implementation, and maintenance. It was difficult to apply the fifth
      dimension, efficacy, because of the differences in study design and purpose of
      the interventions. The strengths and limitations of each project were identified,
      and it was concluded that a combined intervention that incorporates elements of
      both HOPP and STORK would be optimal if it could be implemented at reasonable
      cost.

PMID- 11464428
TI  - Primary care physician job satisfaction and turnover.
AB  - OBJECTIVE: To examine the relationship of personal characteristics,
      organizational characteristics, and overall job satisfaction to primary care
      physician (PCP) turnover. SUBJECTS AND METHODS: A cohort of 507 postresident,
      nonfederally employed PCPs younger than 45 years of age, who completed their
      medical training between 1982 and 1985, participated in national surveys in 1987
      and 1991. Psychological, economic, and sociological theories and constructs
      provided a conceptual framework. Primary care physician personal, organizational,
      and overall job satisfaction variables from 1987 were considered independent
      variables. Turnover-related responses from 1991 were dependent variables.
      Bivariate and multivariate analyses were conducted. RESULTS: More than half (55%)
      of all PCPs in the cohort left at least 1 practice between 1987 and 1991. Twenty
      percent of the cohort left 2 employers. PCPs dissatisfied in 1987 were 2.38 times
      more likely to leave (P < .001). Primary care physicians who believed that third
      party payer influence would decrease in 5 years were 1.29 times more likely to
      leave (P < .03). Non-board certified PCPs were 1.3 times more likely to leave (P
      < .003). Primary care physicians who believed that standardized protocols were
      overused were 1.18 times more likely to leave (P < .05). Specialty, gender, age,
      race, and practice setting were not associated with PCP turnover. CONCLUSIONS:
      Turnover was an important phenomenon among PCPs in this cohort. The results of
      this study could enable policy makers, managed care organizations, researchers,
      and others to better understand the relationship between job satisfaction and
      turnover.

PMID- 11464429
TI  - Physician characteristics and the initiation of beta-adrenergic blocking agent
      therapy after acute myocardial infarction in a managed care population.
AB  - OBJECTIVE: To determine the association between physician characteristics and the
      use of beta-adrenergic blocking agents after acute myocardial infarction in a
      national managed care organization. STUDY DESIGN: Retrospective administrative
      data analysis. PARTICIPANTS AND METHODS: The study cohort consisted of 473
      physicians who prescribed the medications and 578 patients who (1) experienced an
      acute myocardial infarction between January 1, 1995, and December 31, 1996, with
      at least 1 cardiac medication claim within 7 days of hospital discharge; (2) were
      not previously taking beta-adrenergic blocking agents; and (3) had none of
      several defined contraindications to the medication. Using multivariate models,
      we assessed the relation between physician characteristics and initiation of beta
      adrenergic blocking agent therapy, controlling for patient characteristics and
      cardiac treatments. RESULTS: Sixty-two percent of patients filled a prescription
      for beta-adrenergic blocking agents within 7 days of hospital discharge.
      Physician characteristics, including specialty and region of hospitalization,
      were independently associated with the use beta-adrenergic blocking agents.
      Family practice physicians and other noninternists were much less likely than
      cardiologists to prescribe beta-adrenergic blocking agents. The other most
      important predictors of the use of beta-adrenergic blocking agents were region of
      hospitalization and patient age. CONCLUSIONS: Physician characteristics are
      associated with the use of beta-adrenergic blocking agents. Although there are
      opportunities to improve practice for all physicians, family practice physicians
      and noninternists have the most opportunity to improve.

PMID- 11464430
TI  - Electronic prescribing in ambulatory practice: promises, pitfalls, and potential
      solutions.
AB  - OBJECTIVE: To examine advantages of and obstacles to electronic prescribing in
      the ambulatory care environment. DATA SOURCES: MEDLINE and International
      Pharmaceutical Abstract searches were conducted for the period from January 1980
      to September 2000. Key words were electronic prescribing, computerized physician
      order entry, prior authorization, drug utilization review, and consumer
      satisfaction. In September 2000, a public search engine (www.google.com) was used
      to find additional technical information. In addition, pertinent articles were
      cross-referenced to identify other resources. DATA EXTRACTION: Articles, symposia
      proceedings, and organizational position statements published in the United
      States on electronic prescribing and automation in healthcare are cited. DATA
      SYNTHESIS: Electronic prescribing can eliminate the time gap between point of
      care and point of service, reduce medication errors, improve quality of care, and
      increase patient satisfaction. Considerable funding requirements, segmentation of
      healthcare markets, lack of technology standardization, providers' resistance to
      change, and regulatory indecisiveness create boundaries to the widespread use of
      automated prescribing. The potential solutions include establishing a
      standardizing warehouse or a router and gaining stakeholder support in
      implementation of the technology. CONCLUSIONS: Electronic prescribing can provide
      immense benefits to healthcare providers, patients, and managed care. Resolution
      of several obstacles that limit feasibility of this technology will determine its
      future.

PMID- 11464431
TI  - Another theory about healthcare expenditures and inflation refuted by the facts.

PMID- 11464432
TI  - Factors associated with unplanned readmissions following cardiac surgery.
AB  - Cardiac surgery patients are at risk for unplanned readmissions due to the
      various complications they may experience following surgery. The purpose of this
      report is to critically review the literature related to predictors of unplanned
      readmissions of cardiac surgery patients following discharge from the hospital. A
      literature review was conducted from 1989 to 1999 using MEDLINE and CINAHL, with
      the following key words: cardiac surgery, coronary artery bypass surgery,
      recovery, and readmission. The literature revealed that gender and race do have
      an effect on how well a patient will recover following cardiac surgery. It was
      also found that patients with longer lengths of stay due to complications were at
      greater risk for readmission following discharge from the hospital. There was no
      evidence that decreased length of stay for this patient group led to a greater
      number of readmissions. Implications for nurses include the need for improved
      coordination of patient care and implementation of effective discharge planning
      in high-risk patients. Additional research is needed to develop interventions to
      decrease readmissions of women and African Americans and other racial groups
      specific to their particular risk factors for readmission following cardiac
      surgery.

PMID- 11464433
TI  - Interpreting the arterial pressure waveform in the intra-aortic balloon-pumped
      patient.
AB  - This paper reviews arterial pressure waveforms and contrasts the differences in
      waveforms imposed by intra-aortic balloon counterpulsation. It explores questions
      regarding blood pressure interpretation and offers guidelines for practice.

PMID- 11464434
TI  - Role of spirituality in adjustment of patients with advanced heart failure.
AB  - Heart failure is a chronic and progressive disease often characterized by severe
      symptoms, frequent hospitalization, and poor prognosis. It may threaten the
      individual's sense of self and lead to questions related to spirituality. The
      purpose of this qualitative, phenomenologic study was to describe the role of
      spirituality in the adjustment of patients to advanced heart failure. Purposive
      sampling of all patients who presented to two university-affiliated, outpatient
      heart failure clinics was used. Eighty-seven patients were interviewed using a
      semistructured questionnaire. Data were subjected to content analysis and
      thematic coding. Patients described a three-step process where spirituality
      contributed to their adjustment to advanced heart failure: development of regret
      regarding past behaviors and lifestyles; the search for meaning within the
      present experience of heart failure; and the search for hope for the future and
      reclaiming of optimism. Assessment and interventions that include a spiritual
      dimension can facilitate the adjustment of patients to advanced heart failure.

PMID- 11464435
TI  - Dofetilide: a new class III antiarrhythmic for the management of atrial
      fibrillation.

PMID- 11464436
TI  - Change from a North American setting to a European setting: impressions from a NY
      trained adult nurse practitioner.
AB  - There are many challenges that an American-trained nurse practitioner faces in
      Switzerland. Having an international perspective, I will be able to combine the
      best of two settings. My goal is to be a role model for the ways in which
      advanced nursing practice can be an asset in the health care setting and to
      inspire nurses to pursue this path in preventive, rehabilitative, or acute
      cardiovascular settings throughout Switzerland.

PMID- 11464437
TI  - Cardiac surgery 2001: what's hot, what's not.

PMID- 11464438
TI  - What is this atrioventricular conduction abnormality occurring after electrical
      cardioversion for atrial flutter?

PMID- 11464439
TI  - Treating obesity: a new target for prevention of coronary heart disease.
AB  - Recognition by the American Heart Association that obesity is a major modifiable
      risk factor for coronary heart disease has prompted health providers to take a
      more active role in obesity management. Obesity has long been known to accompany
      a host of chronic diseases, e.g., type II diabetes, hypertension, and
      dyslipidemia. We now recognize that obesity is itself a chronic disease with a
      complex etiology; like diabetes and hypertension, it is treatable with a similar
      chronic disease treatment model. Relatively modest weight loss confers
      disproportionate health benefits, improving a roster of risk factors. Diet,
      exercise, and behavior modification still compose the gold standard of treatment.
      If these measures fail, medication and surgery should be considered for
      appropriate patients. With current techniques, many patients can achieve
      realistic weight goals that can be maintained over the long term. Published
      management guidelines can now assist in integrating the practical applications of
      obesity-related research findings into everyday clinical practice.

PMID- 11464440
TI  - Nutritional status and well being. Is there a relationship between body mass
      index and the well-being of older people?
AB  - Poor nutritional status may impair well being indirectly as a consequence of
      increased morbidity and decline in functional status. The aim of this study was
      to examine the independent effect of body mass index on the well being of older
      people. Thirty one hospital-based patients over 65 years of age were studied.
      Well being was assessed using the Philadelphia Geriatric Center Morale Scale
      (PGCMS)--anglicised version. Body mass index and well being were assessed on
      admission to hospital and at three months. At follow-up, a significant
      correlation was observed between body mass index and PGCMS values. Further
      analysis showed that this relationship was linear, with poor nutritional status
      being associated with low levels of well being and good nutritional status being
      associated with the highest levels of well being. High or low body mass index was
      able to predict the PGCMS score with a poor sensitivity of 44% and specificity of
      96%. When the contribution of potential confounding variables was analysed, body
      mass was found to have no significant independent effect on well being. Instead,
      the presence of depression was the most powerful predictor of levels of well
      being. In conclusion, this study has demonstrated that nutritional status, as
      indicated by body mass index, has no detectable independent effect on well being.
      However, measurement of nutritional status may still have a role in the
      assessment of well being, in that, while the finding of a low body mass index
      cannot be taken as indicative of low levels of well being, the finding of a high
      body mass index is likely to indicate adequate well being. Further studies,
      however, are required in this area that would involve larger numbers of subjects
      and alternative measures of nutritional status and well being.

PMID- 11464441
TI  - The treatment of coronary heart disease: an update. Part 1: An overview of the
      risk factors for cardiovascular disease.
AB  - Cardiovascular disease (CVD) is the main cause of death. Atherosclerosis of
      coronary arteries is responsible for almost all cases of CVD. The term 'risk
      factor' describes all those characteristics found in healthy individuals that are
      independently related to subsequent development of CVD. It includes modifiable
      biochemical and physiological characteristics, such as hypercholesterolaemia,
      hypertension, cigarette smoking, diabetes mellitus, obesity and low HDL
      cholesterol levels, as well as non-modifiable personal characteristics, such as
      age, gender and family or personal history of early onset CVD. In addition to the
      'classic' risk factors mentioned above, several other variables have been
      implicated as predictors of CVD: left ventricular hypertrophy; infectious agents;
      markers of inflammation; oxidative stress; and increased levels of fibrinogen,
      triglycerides, homocysteine and Lp(a)]. However, controversy exists regarding the
      exact role of these variables in the pathogenesis of atherosclerosis.
      Furthermore, there are no conclusive data showing that the modification of these
      variables is associated with a decrease in the incidence of cardiovascular
      events. Nevertheless, these 'new' risk factors should be taken into account in
      patients with CVD without established risk factors.

PMID- 11464442
TI  - The treatment of coronary heart disease: an update. Part 2: Mortality trends and
      main causes of death in the Greek population.
AB  - The Seven Countries Study, carried out in the 1960s, showed a low cardiovascular
      disease (CVD) mortality in the Greek population. Since then, although the age
      adjusted all-cause mortality has gradually and steadily decreased, CVD mortality
      has increased, mainly due to a rise in ischaemic heart disease (IHD) mortality,
      and, more specifically, myocardial infarction (MI). The number of MIs per 100,000
      men aged 30-69 years increased from 195 in 1981 to 297 in 1988 and from 35 to 52
      in women, respectively. Age-adjusted IHD mortality in men aged 45-74 years almost
      doubled from 1956 to 1978. The rate of increase slowed down for a decade and
      since 1990 it has declined slightly. In women, the age-adjusted IHD mortality
      increased, but to a lesser degree until 1990, and then it started to decline.
      Cerebrovascular mortality was higher than IHD mortality in women and equal to IHD
      mortality in men in the late 1950s and early 1960s, but it started to decrease in
      1972 in men, and in 1973 in women. Cancer mortality is the second commonest cause
      of death in both genders. Age-adjusted cancer mortality (in those aged 45-74
      years) increased slightly in men until 1979 and then remained stable. In women,
      it remained stable until 1991 and then started to decline. The eradication of
      malaria and rheumatic fever, the decrease in infectious diseases, the improvement
      of the medical care system and the rise of the population's socio-economic level
      achieved during the last five decades in Greece have reduced all-cause mortality.
      On the other hand, the changes in lifestyle (lack of physical exercise, new
      dietary habits) have resulted in a higher IHD mortality. However, this increase
      is less than would be expected, taking into account the rise in blood cholesterol
      levels and the high prevalence of smoking. The recent small decline in IHD
      mortality is probably attributable to better treatment of IHD rather than to
      preventive measures.

PMID- 11464443
TI  - The treatment of coronary heart disease: an update. Part 3: Statins beyond
      cholesterol lowering.
AB  - Statins may have additional properties beyond diminishing low-density lipoprotein
      (LDL) cholesterol levels. These actions could reduce the risk of vascular events.
      For example, these lipid lowering drugs act on the vascular endothelium, smooth
      muscle, haemostatic factors and the vessel wall. There are several differences in
      how statins act on these systems. These observations, in turn, lead to the
      conclusion that all statins may not be equally effective in terms of vascular
      disease prevention.

PMID- 11464444
TI  - The treatment of coronary heart disease: an update. Part 4: Acute ischaemic
      coronary syndromes.
AB  - There have been several recent developments in the diagnosis, risk stratification
      and treatment of acute ischaemic coronary syndrome (AICS). These include the use
      of troponins for the diagnosis and risk stratification of AICS. The use of
      glycoprotein IIb/IIIa inhibitors and angioplasty with stenting has altered the
      prognosis associated with AICS. This brief review considers these issues.

PMID- 11464445
TI  - The treatment of coronary heart disease: an update. Part 5: Selected comments and
      questions.
AB  - Vasospasm is probably the cause of myocardial infarction (MI) in only a few
      cases. There are differences between statins and therefore they may not all be
      equally effective. Several cardiovascular risk factors need to be assessed in
      high-risk patients.

PMID- 11464446
TI  - A comparison of simvastatin and atorvastatin up to maximal recommended doses in a
      large multicenter randomized clinical trial.
AB  - OBJECTIVE: At higher doses, simvastatin has been shown to produce significantly
      greater increases in high-density lipoprotein (HDL) cholesterol and
      apolipoprotein (apo) A-I than atorvastatin. To extend and confirm these findings,
      a 36-week, randomized, double-blind, dose-titration study was performed in 826
      hypercholesterolemic patients to compare the effects of simvastatin and
      atorvastatin on HDL cholesterol, apo A-I, and clinical and laboratory safety.
      PRIMARY HYPOTHESIS: Simvastatin, across a range of doses, will be more effective
      than atorvastatin at raising HDL cholesterol and apo A-I levels. METHODS: A total
      of 826 hypercholesterolemic patients were enrolled in this double-blind,
      randomized, parallel, 36-week, dose-escalation study. Patients randomized to
      simvastatin received 40 mg/day for the first 6 weeks, 80 mg/day for the next 6
      weeks, and remained on 80 mg/day for the final 24 weeks. Patients randomized to
      atorvastatin received 20 mg/day for the first 6 weeks, 40 mg/day for the next 6
      weeks, and 80 mg/day for the remaining 24 weeks. RESULTS: During the first 12
      weeks of the study, simvastatin increased HDL cholesterol and apo A-I more than
      the comparative doses of atorvastatin, while producing slightly lower reductions
      in low-density lipoprotein (LDL) cholesterol and triglycerides. At the maximal
      dose comparison, simvastatin 80 mg and atorvastatin 80 mg, the HDL cholesterol
      and apo A-I differences favoring simvastatin were larger than at the lower doses.
      In addition, at the maximal dose comparison, the incidence of drug-related
      clinical adverse experiences was approximately two-fold higher with atorvastatin
      80 mg than with simvastatin 80 mg (23 versus 12%, p < 0.001), due predominantly
      to a greater incidence of gastrointestinal symptoms with atorvastatin (10 versus
      3%, p < 0.001). The incidence of clinically significant alanine aminotransferase
      elevations was also higher with atorvastatin 80 mg than with simvastatin 80 mg
      (3.8 versus 0.5%, p < 0.010), especially in women (6.0 versus 0.6%). CONCLUSIONS:
      At the doses compared in this study, simvastatin led to greater increases in HDL
      cholesterol and apo A-I levels than atorvastatin. At the maximum dose comparison,
      there were fewer drug-related gastrointestinal symptoms and clinically
      significant aminotransferase elevations with simvastatin.

PMID- 11464447
TI  - From HER2 to herceptin.
AB  - HER2 overexpression occurs in 25% of breast cancers and seems to correlate with
      poor prognosis. HER2 overexpression may predict tamoxifen failure and different
      response rates to chemotherapeutic agents such as the taxanes and anthracyclines.
      The detection of HER2 and its overexpression is performed using fluorescent in
      situ hybridisation (FISH) and/or immunohistochemistry (IHC). Trastuzumab
      [Herceptin (H)] is a humanised IgG monoclonal antibody specific for the growth
      factor receptor HER2. Pre-clinical trials using monoclonal antibodies have shown
      inhibition of breast tumour growth in athymic nude mice. Phase II and III
      clinical trials have evaluated the efficacy and safety of Herceptin in women with
      metastatic breast cancer in combination with other agents and as a single agent.
      Currently, Trastuzumab and paclitaxel is the only combination indicated for the
      treatment of patients with metastatic breast cancer whose tumours overexpress
      HER2. It is also indicated as a single agent in women with HER2-overexpressing
      metastatic breast cancer that has progressed after previous chemotherapy.
      Herceptin is a well-tolerated drug and the side-effects that are commonly seen
      with chemotherapy, such as neutropenia, alopecia and mucositis, are rarely
      observed. The main risk factors for cardiotoxicity are concurrent or previous
      anthracycline exposure. The potential role of Herceptin in the adjuvant setting
      is currently being evaluated.

PMID- 11464448
TI  - Hypertriglyceridemia: a review of clinical relevance and treatment options: focus
      on cerivastatin.
AB  - The triglyceride (TG) level is one of several lipid parameters that can aid
      prediction of coronary heart disease (CHD) risk. An elevated plasma TG level is
      strongly associated with an increased risk of CHD. Hypertriglyceridemia, the
      second most common dyslipidemic abnormality in hypertensive subjects after
      increased low-density lipoprotein cholesterol (LDL-C), is defined by the National
      Cholesterol Education Programme (NCEP) as a fasting TG level of > 2.26 mmol/l (>
      200 mg/dl) and is recognised as a primary indicator for treatment in type IIb
      dyslipidemia. Raised TG levels can be present in individuals at risk for CHD when
      the total cholesterol is normal. However, not all individuals with raised TG
      levels have increased risk of CHD. Factors such as: diet, age, lifestyle, and a
      range of medical conditions, drug therapy and metabolic disorders, can all affect
      the TG level. In some of these circumstances, other factors protect against the
      risk of CHD, and can minimise or negate the effect of the risk factors present.
      Although TG reducing therapy has been shown to be associated with an improved
      clinical outcome, more research is needed to determine whether this is an
      independent effect of TG reduction or an effect of normalising the overall lipid
      profile in hypertriglyceridemic patients. Further trials are required to quantify
      the clinical benefits of lowering TG to 'target' levels and to confirm targets
      defined by NCEP-II (shown in Table 1). The role of TG in CHD pathogenesis is
      thought to involve several direct and indirect mechanisms, such as effects on the
      metabolism of other lipoproteins, transport proteins, enzymes, and on coagulation
      and endothelial dysfunction. More research is required to fully elucidate the
      role of TG, the ways in which it can influence other risk factors and the
      mechanism of its own more direct role in the atherogenic process. Patients with
      hypertriglyceridemia have been shown to respond well to dietary control and to
      the use of lipid lowering drugs such as 3-hydroxy-3-methylglutaryl-Coenzyme A
      (HMG CoA) reductase inhibitors (known as statins), fibrates and nicotinic acids.
      However, recent retrospective real-life clinical studies show that only 38% of
      patients receiving some form of lipid-lowering therapy achieved NCEP-defined LDL
      C target levels, demonstrating the need for the use of more aggressive treatment.
      In hypertriglyceridemic patients, the newer statins, cerivastatin and
      atorvastatin, have shown comparable efficacy in reducing TG compared with the
      older statins. Achieving NCEP target lipid levels has been shown to reduce the
      risk of cardiovascular disease in dyslipidemic individuals, including high-risk
      patient groups such as those with additional risk factors, existing heart
      disease, diabetes mellitus and metabolic syndrome. Although the latest clinical
      studies investigating combination therapies, i.e. dual therapy with both a statin
      and a fibrate, have demonstrated them to be effective for overall control of
      lipid parameters and reducing coronary events, it is not yet clear whether this
      offers any significant advantage over monotherapy. Results from ongoing longer
      term end-point clinical studies may provide further information in this area and
      consequent reviews of primary care management policies for dyslipidemia. Statin
      monotherapy may be a reliable option for primary care treatment of dyslipidemia
      (including hypertriglyceridemia).

PMID- 11464449
TI  - Synthetic statins: more data on newer lipid-lowering agents.
AB  - Extensive trial evidence supports the use of hydroxy-methyl-glutaryl-CoA
      reductase inhibitors (HMG-CoA-RI; statins) in atherosclerotic disease. Statins
      can be divided into two broad groups: the 'natural' statins derived from a fungal
      metabolites, and synthetic compounds. Whether all statins have similar anti
      atherosclerotic properties, or whether these actions are specific to the
      'natural' statins, is controversial. This commentary reviews the differences
      between natural and synthetic statins with regard to lipid-lowering and non-lipid
      lowering effects, including their action on the acute phase reactant C-reactive
      protein. Among the newer synthetic statins, fluvastatin has some positive end
      point evidence while cerivastatin shares many biochemical properties with the
      'natural' statins. Extensive clinical trial programmes are underway with both
      atorvastatin and cerivastatin. These trials will give a definitive answer to the
      question of whether synthetic statins are as equally efficacious as 'natural'
      statins in preventing atherosclerotic events.

PMID- 11464450
TI  - Eprosartan provides safe and effective long-term maintenance of blood pressure
      control in patients with mild to moderate essential hypertension.
AB  - Control of hypertension is hindered by the incidence of adverse events associated
      with therapy, which can result in low patient compliance. Specific angiotensin II
      receptor subtype AT1 blockers offer an alternative to the angiotensin converting
      enzyme inhibitors in the treatment of hypertension, as the incidence of side
      effects may be lower. This open-label study was designed to investigate the long
      term safety and efficacy of the AT1 receptor blocker, eprosartan, in patients
      with mild to moderate essential hypertension (sitting diastolic blood pressure >
      or = 95 mmHg and < or = 114 mmHg). 706 patients from 55 centres in the USA and
      three centres in Canada were randomised to receive once-daily eprosartan (400-800
      mg) alone or in combination with hydrochlorothiazide (HCTZ). The study consisted
      of five periods: screening (day 1), run-in (2-4 weeks), titration (3-15 weeks),
      maintenance (12-24 months) and follow-up (5-7 days). Safety evaluations included
      incidences of adverse events and changes in laboratory tests, vital signs and
      electrocardiograms. Efficacy assessments included effects on blood pressure (BP)
      and fasting concentrations of lipids and glucose. The maintenance period was
      completed at 12 months by 583 (83.3%) patients and at 24 months by 311 (44.4%)
      patients. In total, 396 (56.1%) patients completed the study according to
      protocol. Once-daily eprosartan was well tolerated either alone or in combination
      with HCTZ, irrespective of the study dose administered. Patients treated with
      eprosartan had a safety profile similar to that reported in short-term placebo
      controlled studies. The most frequently reported adverse event was upper
      respiratory tract infection. The incidence of adverse events was not affected by
      age or race, and, although events increased with the addition of HCTZ, they were
      generally not severe. The beneficial effect on BP was maintained throughout
      treatment. For the majority of patients, HDL cholesterol, triglyceride and
      glucose levels remained within the reference levels at all doses and timepoints.
      In summary, eprosartan provides reliable blood pressure control in a high
      proportion of patients, with a safety profile similar to that seen with placebo
      in short-term, placebo-controlled trials. By providing long-term safety and
      efficacy, eprosartan may have the potential to increase patient compliance, a
      significant issue in the treatment of hypertension in all patient types.

PMID- 11464451
TI  - [A challenge to conquest of neurological diseases].
AB  - For the last three decades, neurology has witnessed remarkable progress in both
      basic sciences and clinical researches. They include detection of abnormal genes
      in common degenerative and metabolic diseases, clarification of brain mechanisms
      of movement and cognition with neurophysiology including unit recording from
      basal ganglia neurons, neuroimaging and neuropsychology tests. Treatment of
      intractable chronic diseases has also progressed. Medical, surgical and
      immunosuppressive treatment for Parkinson's disease, immunological diseases, and
      for certain metabolic diseases are examples. Neurologists in Japan contributed in
      research progress in the various fields. However, services in clinical medicine
      have devoted mainly in neurodegenerative, immunological diseases and myopathy.
      Promotion of nationwide clinical service for cerebrovascular disease, epilepsy
      and dementia is required. Research in neurology in the next century should be
      promoted in various fields with different methodology and targets; genes,
      molecular mechanisms, cellular activity, neural networks, brain as a whole and a
      human subject. Particularly integrated function of he brain shall be studied
      thoroughly not only from biological but also from psychological and social point
      of view. Leaders in neurology in Japan, particularly professors of neurology have
      been asked to chair all the activities of education, research and clinics. Merits
      of this system were reflected in connection of clinical and research data,
      resulting in establishment of new disease showing unusual combination of symptoms
      and signs. In future, coordination among specialists in different fields are
      required for further promotion of clinical researches and training of
      neurologists. Qualified neurological services in ordinary clinics can be achieved
      with cooperation of personnels in a team where neurologists are required to play
      a key role aiming at assurance of best QOL for patients and families.

PMID- 11464452
TI  - [Functional and pathophysiological models of the basal ganglia: therapeutic
      implications].

PMID- 11464453
TI  - [Molecular mechanisms of neurotransmission].
AB  - Neurotransmission is regulated by neurotransmitters at the synapses in the
      neuronal circuits. Main neurotransmitters are classified into the groups of amino
      acids, amines, purines, peptides, and nitric oxide. In principle,
      neurotransmitters except peptides are synthesized in the presynaptic
      neuroterminals from the precursors by the synthesizing enzymes, stored in the
      synaptic vesicles, released by exocytosis into the synaptic cleft, combined with
      the postsynaptic membrane receptors, and induce a series of signal transduction
      to produce acute, short-term, or long-term physiological effects. Termination of
      the neurotransmission is carried out either by re-uptake into presynaptic nerve
      terminals through plasma membrane transporters and storage into synaptic vesicles
      through vesicular transporters or by degradation through metabolizing enzymes
      (acetylcholine and peptides). Almost all genes related to neurotransmitters have
      been cloned and the structures of the genes and the protein products have been
      characterized. Molecular mechanisms of neurotransmission have been elucidated by
      mouse molecular genetics such as transgenic or knockout mice. Over-expression of
      human tyrosine hydroxylase (TH). the rate-limiting enzyme of catecholamine
      synthesis, in transgenic mice (Kaneda et al, Neuron 6, 583-584, 1991) or
      conversion of norepinephrine neurons to epinephrine neurons (Kobayashi et al,
      Proc Natl Acad Sci USA 89, 1631-1635, 1992) does not significantly change the
      phenotype due to compensatory mechanisms such as receptor down-regulation. In
      contrast, TH (-/-) mutant mice die at perinatal period due to heart failure
      caused by norepinephrine deficiency in the sympathetic neurons (Kobayashi et al,
      J Biol Chem 270, 27235-27243, 1995). TH (+/-) mice show a partial decrease in
      norepinephrine and a modest memory impairment (Kobayashi et al, J Neurosci 20,
      2418-2426, 2000). One problem with adult phenotype in transgenic or knockout mice
      is that mutations cause the confounding effect of the developmental compensation.
      Thus conditional knockout of a specific type of neurons at a definite time after
      birth is required. Immunotoxin mediated conditional cell targeting (IMCT)
      (Kobayashi et al, Proc Natl Acad Sci 92, 1132-1136, 1995) is a novel transgenic
      technique for elucidating the function of a neuron in a neuronal circuit. Human
      molecular genetics of genetic neurological diseases are also useful for
      elucidating molecular mechanisms of neurotransmission. Autosomal dominant dopa
      responsive dystonia (DRD) (Segawa's disease) with mutations of GTP cyclohydrolase
      I (Ichinose et al, Nature Genet 8, 236-242, 1994) causes a partial decrease in
      dopamine in the nigrostriatal dopamine neurons and produces a dystonia phenotype
      (Segawa's syndrome). In contrast, autosomal recessive GTP cyclohydrolase I
      deficiency with complete loss of the enzyme activity produces deficiencies of
      dopamine, norepinephrine, and serotonin and complex phenotypes with severe
      neurological symptoms (Ichinose et al, J Biol Chem 270, 10062-10071, 1995).

PMID- 11464454
TI  - [Prediction on the medical care system for the aged people in the new century].
AB  - Japan has become the country with the longest life expectancy in the world in
      about 25 years. Among many factors for this success, the medical care system,
      including the health insurance for everyone, played the important role, which has
      been evaluated as the best in the world. However, since the national economy in
      Japan has become recently suppressed it has become one of the big political
      problems to keep this system as same as before. In addition, the medical expenses
      for the elderly and aged people is now as high as 40% of all. In this meaning, we
      should create the better system by ourselves, based on ethical criteria,
      harmonized with the progress of medicine. In April of 2000, the new long term
      care system was introduced aiming the self independence of aged people. Now, the
      medical and long term care system has become unified into one toward the ideal
      society in the future. In this paper, the ideal medical care system, especially
      for the aged people was discussed. Needless to say, the medical care system
      should have widely view to the future. The progress of medicine, high technology
      and health promotion will play very important parts to create the ideal society
      in future. If any geriatric diseases including senile dementia will be settled in
      near future, the medical care system for the aged will change completely. In
      addition, the nationwide campaign of health promotion will induce excellent
      results. Thus the society in the future will become much brighter and happier. In
      this meaning, health promotion, medical care, and welfare systems should be
      unified into one system. The expenses for these systems should be regarded as the
      investments expecting the huge profit in health and happiness in the future.

PMID- 11464455
TI  - [Triplet repeat disease, with particular emphasis of spinal and bulbar muscular
      atrophy (SBMA)].
AB  - Spinal and bulbar muscular atrophy (SBMA) is an X-linked neurodegenerative
      disease caused by the expansion of a CAG repeat in the first exon of the androgen
      receptor (AR) gene. To date, eight CAG-repeat diseases have been identified,
      including spinal and bulbar muscular atrophy (SBMA). Huntington's disease (HD),
      dentatorubralpallidoluysian atrophy (DRPLA) and five spinocerebellar ataxias
      (SCAs 1, 2, 3, 6, 7). These disorders likely share a common pathogenesis caused
      by the gain of a toxic function associated with the expanded polyglutamine tract.
      Several mechanisms have been postulated as a pathogenic process for
      neurodegeneration caused by the expanded polyglutamine tract. Processing of the
      polyglutamine containing proteins by proteases liberate truncated polyglutamine
      tract, which may cause neurodegeneration as demonstrated in transgenic mice and
      transfected cells. In addition to cellular toxicity, truncated and expanded
      polyglutamine tracts have been shown to form intranuclear inclusions (NI). The
      NIs formed by the disease protein are a common pathological feature of these
      diseases. In SBMA, NIs containing AR protein have been observed in regions of
      SBMA central nervous system susceptible to degenerations. Transcriptional factors
      or their cofactors, such as cerb or creb-binding protein (CBP) sequestrated in
      the NI may alter the major intracellular transcriptional signal transduction, and
      ultimately may result in neuronal degeneration. The ubiquitin-proteasome pathway
      may also contribute to the pathogenesis of CAG-repeat diseases. As for the
      therapeutic strategies, many possibilities have been demonstrated. Overexpression
      of Hsp70 and Hsp40 chaperones act together to protect a cultured neuronal cell
      model of SBMA from a cellular toxicity of expanded polyglutamine tract.

PMID- 11464456
TI  - [Recent progress in electrodiagnostic tests in clinical neurology].
AB  - Electrodiagnostic testings including electromyography have become increasingly
      important tools in clinical practice of neurology. These tests should not merely
      be referred to a technician, but be viewed as a clinical tool used by a
      neurologist. Recent advances in clinical electromyography, nerve conduction
      tests, and tests for axonal function including the newly developed threshold
      electrotonus are reviewed. These not only serve as a diagnostic tool, but also
      are useful in clinical trials by providing an objective parameter of nerve
      function. Computerized threshold tracking techniques such as threshold
      electrotonus enable us to monitor molecular events in various ion channels in
      axons of patients. Further development is expected toward clinical molecular
      neurophysiology.

PMID- 11464457
TI  - [Diagnosis and recent treatment of migraine].
AB  - This lecture discusses prevalence, diagnosis and recent treatment of migraine in
      Japan. It particularly emphasizes the necessity for better medical delivery to
      patients with migraine. The nationwide population study showed that migraine is
      just as common a disorder as in other countries. The overall prevalence of
      migraine was 8.4% among people aged 15 years or older. Severity of migraine was
      similar to previous reports from other countries. Migraine sufferers in Japan do
      not consult a physician regularly for the problem. Yet, approximately 70% of the
      migraine sufferers complained that migraine headache disturbed their daily
      activity to a major degree. With many migraine sufferers who deserve medical
      care, the necessity for improved medical care is beginning to be widely
      recognized. New medicine such as sumatriptan is on market now and its proper
      clinical use is important.

PMID- 11464458
TI  - [How to examine a patient with higher cerebral dysfunction].
AB  - The mysterious maneuvers of the neuropsychological examination actually conceal
      the very intellectual process by which diagnosis is obtained. Five features that
      are usually sufficient to diagnose aphasia are 1) spontaneous speech, 2) speech
      comprehension, 3) repetition, 4) reading aloud with comprehension, and 5)
      writing. In spontaneous speech, fluent aphasics have normal rhythm, melody, and
      well-articulated sentence, but the speech is filled with paraphasias. The speech
      of non-fluent aphasics is slow, labored, and poorly articulated. When patients
      with spatial neglect are asked to perform a variety of tasks in space, they
      neglect the hemispace contralateral to their lesion. For example, when asked to
      draw a picture of a flower, they may draw only a half of the flower. The patients
      may fail to cross out lines distributed over a page. Amnesic patients, despite
      normal scores on psychometric tests of intelligence and normal performances on
      immediate memory, show significant impairments in new learning (anterograde
      amnesia) and remote memory (retrograde amnesia). In this article, The author also
      explained about two topics briefly of language functions (tactile reading) and
      hemispatial neglect (reference frames).

PMID- 11464459
TI  - [Recent advance in epileptology].
AB  - Nowadays epilepsy is classified according to the international classification of
      epilepsies, epileptic syndromes and related disorders proposed by International
      League Against Epilepsy (ILAE, 1989). Among these epilepsies and epileptic
      syndromes, I detailed the clinical symptomatology and the clinical significance
      of benign familial neonatal convulsions, juvenile myoclonic epilepsy, epilepsy
      with myoclonic absence, mesial temporal lobe epilepsy and chronic progressive
      epilepsia partialis continua of childhood. Of 218 patients with temporal lobe
      resection who were followed for over 2 years, 172 patients or 79% were seizure
      free according to Engel's criteria of seizure outcome after surgical treatment.
      Of 66 patients with extra-temporal lobe epilepsy, 43 patients or 65% were seizure
      free. From the postsurgical outcome I talked about the need of strict presurgical
      evaluation to have the good postsurgical outcome. The neuropathology of
      surgically resected 278 specimens of temporal lobe epilepsy was mesial temporal
      sclerosis in 184, neuroepithelial tumors in 66, cortical malformation in 11,
      vascular anomaly in 13, and others in 4. Thirty-nine of resected 66 specimens of
      extra-temporal lobe epilepsies were cortical malformation. I presented the recent
      progress of genetic study in epilepsies and stressed the importance of correct
      diagnosis of epilepsy for genetic study.

PMID- 11464460
TI  - [Recent advances in autonomic function tests].
AB  - Recent advances in medical technology introducing various new autonomic function
      tests. We introduced five new autonomic function tests, these are initial heart
      rate response to postural change, monitoring of cerebral circulation by near
      infrared spectroscopy, sympathetic skin tests including sympathetic sweat
      response and sympathetic flow response, pressure flow study and videourodynamics.
      Initial heart rate response to voluntary standing reveals two types of heart rate
      increase, initial one is due to parasympathetic suppression and late one is due
      to sympathetic activity. Near-infrared spectroscopy could detect the amount of
      local blood volume, and by using this test we occasionally noted a discrepancy of
      systemic blood pressure and cerebral circulation. Sympathetic skin test revealed
      relatively well preserved flow response whereas sweat response is often severely
      impaired in central nervous system disease. Pressure flow study could
      differentiate the impaired detrusor contraction and increased outlet resistance
      in patients with impaired micturition. Videourodynamics is the useful method to
      visualize the lower urinary disorders.

PMID- 11464461
TI  - [Neurology of eye movements].
AB  - Eye movements are necessary for clear and stable vision, for which images of the
      world should be brought to the fovea and be held steady on the retina. The main
      types of eye movements consist of saccadic eye movements, vergence, vestibular
      eye movements, smooth pursuit eye movements and eye movements for visual
      stabilization. Saccades are fast eye movements and have consistent relationship
      between their peak velocity and the size of the movements. The burst neurons in
      the brainstem are the generator of saccades and receive projections from the
      frontal eye field, supplementary eye field, parietal eye field, basal ganglia,
      superior colliculus and cerebellum. Saccades are evaluated by a speed and
      accuracy of the size. There are different types of saccade, such as visually
      triggered saccades, antisaccades, memory-guided saccade and predictive saccades.
      The specific test paradigms of saccades may show the localization and the type of
      diseases. Opsoclonus, flatter-like oscillation, ocular myoclonus, square-wave
      jerks are characteristic involuntary eye movements. Syndromes of the paramedic
      pontine reticular formation, medial longitudinal fascicules and one-and-a-half
      syndrome are caused by disease of the pons.

PMID- 11464462
TI  - [Risk factors for Alzheimer's disease].
AB  - Apolipoprotein E (apoE) is the major risk factor, besides aging, for Alzheimer's
      disease (AD). Many hypotheses have been proposed to explain the mechanism whereby
      one of the isoforms of apoE, apoE4, could cause AD. We have been conducting
      studies on the pathogenic roles of apoE from the viewpoint of its physiological
      function. We previously reported that one detrimental effect of apoE4 on neuronal
      viability can be induced by alteration in intracellular cholesterol metabolism.
      In brains of patients with AD, there is a common pathological process, called the
      amyloid cascade. Therefore, one of the central questions regarding the pathogenic
      roles of apoE in the development of AD is how apoE4 enhances deposition of
      amyloid b-protein (A beta). In relation to this issue, evidence is now
      accumulating to show that the metabolism of amyloid precursor protein (APP) and A
      beta can be modulated by cellular cholesterol. Our recent studies revealed that a
      novel A beta with a unique ability to accelerate fibril formation of soluble A
      beta is generated in the presence of cellular cholesterol. These lines of
      evidence suggest that the alteration of cholesterol metabolism in neurons due to
      aging and/or expression of apoE4 may be a prerequisite for the development of AD.

PMID- 11464463
TI  - [beta-amyloid cascade: current status and future directions].
AB  - The deposition of amyloid beta peptides (A beta) is one of the pathological
      hallmarks of Alzheimer's disease (AD) brains. A beta are composed of 40-42 amino
      acid peptides that are proteolytically cleaved from beta APP. The deposition as
      diffuse plaques of a species of A beta ending at the 42nd residue (A beta 42) is
      one of the earliest pathological changes of AD. Importantly, mutations in beta
      APP genes located in positions flanking the A beta sequences have been shown to
      cosegregate with the clinical manifestations of AD in a subset of familial AD
      (FAD) pedigrees. Moreover, mutations in presenilin (PS) 1 and 2, novel polytopic
      membrane proteins identified as causative molecules for the majority of FAD, also
      increase the production of A beta 42. These results support the notion that A
      beta (42) plays a key role in the cascadic development of AD. Recently, PS 1 and
      PS 2 are shown to be the catalytic subunits of gamma-secretase that cleave the
      intramembrane segments of beta APP and Notch. Future therapeutic approaches to
      reduce amyloid deposition, including inhibitors for beta- and gamma-secretases,
      as well as beta-amyloid vaccine therapy, raise high hopes towards the cure and
      prevention of AD, although the outcome thereof would be key to the consistency of
      amyloid cascade hypothesis.

PMID- 11464464
TI  - [Roles of mitochondrial dysfunctions in Alzheimer's disease--contribution of
      deficiency of ALDH 2].
AB  - Mitochondrial aldehyde dehydrogenase 2 (ALDH 2) deficiency is caused by a mutant
      allele in the Mongoloids. To examine whether genetic constitutions affecting
      aldehyde metabolism influence the risk for late-onset Alzheimer's disease (LOAD),
      we performed a case-control study in the Japanese population on the deficiency in
      ALDH 2 caused by the dominant-negative mutant allele of the ALDH 2 gene (ALDH 2 *
      2). In a comparison of 447 patients with sex, age and region matched non-demented
      controls, the genotype frequency carrying the ALDH 2 * 2 allele was significantly
      higher in the patients than in the controls (p = 0.001, Odds ratio 1.6). Logistic
      regression analysis indicates that carriage of the ALDH 2 * 2 allele is an
      independent risk for LOAD of the epsilon 4 allele of the apolipoprotein E gene
      (APOE-epsilon 4) (p = 0.002). Moreover, the odds ratio for LOAD in carriers of
      the ALDH 2 * 2 allele was almost twice that in non-carriers irrespective of
      status with regard to the APOE-epsilon 4 allele. Among patients homozygous for
      the APOE-epsilon 4 allele, age at onset of LOAD was significantly lower in those
      with than without the ALDH 2 * 2 allele. In addition, dosage of the ALDH 2 * 2
      allele significantly affected age at onset of patients homozygous for the APOE
      epsilon 4 allele. These results indicate that the ALDH 2 deficiency is a risk for
      LOAD, synergistically acting with the APOE-epsilon 4 allele.

PMID- 11464465
TI  - [The progress of Alzheimer's disease research biomarkers--sensitivity and
      specificity].
AB  - Rapid growth of dementia patients prompts improvement of medical and care
      systems. For this reason, biological markers for Alzheimer's disease are
      necessary, which enable us detect Alzheimer's disease before onset of dementia
      and evaluate drug effects on evidence based procedure. Here, we summarized the
      developing field of biological markers and reported recent results of large-scale
      multicenter study of CSF tau and A beta for clinical practice.

PMID- 11464466
TI  - [Thrombolytic therapy for acute ischemic stroke].
AB  - In this paper, results of the recent clinical trials were reviewed, and problems
      in treating patients with thrombolysis were discussed. Data generated from
      randomized controlled trials over the past few years have shown that acute
      intervention can improve neurological outcome in patients with ischemic stroke.
      Intravenous recombinant tissue plasminogen activator has become established as an
      acute treatment for stroke. Intra-arterial thrombolysis is a developing modality
      for the treatment of the acute stroke that shows promise in restoring cerebral
      arterial supply. However, thrombolysis have not approved yet in any forms in
      Japan. Under this circumstance, thrombolysis should be carried out in GCP
      compatible clinical trials, so far. The overall results of a clinical trial
      cannot necessarily generalized to all patients in the trial and all similar
      future patients. A difference between settings of a clinical trial and of general
      practice should be also noted. Early recognition of stroke symptoms and immediate
      transfer to a suitable treatment facility should bring thrombolysis to a larger
      number of stroke victims. Finally, successful treatment is due in part to
      selecting patients who are not at increased risk for intracranial hemorrhage
      based on clinical and imaging features, and therefore rapid in-hospital triage
      protocols are mandatory.

PMID- 11464467
TI  - [Recent progress in intravascular neurosurgery for the treatment of
      cerebrovascular disease].
AB  - With the recent advances in the devices and techniques in intravascular
      neurosurgery such as microcatheters or a digital subtraction angiography,
      intravascular neurosurgery plays an important role for the treatment of
      cerebrovascular disease. We describe here, a recent progress in intravascular
      neurosurgery for the treatment of cerebrovascular disease. As a treatment of
      cerebrovascular disease, we discuss the treatment of cerebral aneurysm using
      Guglielmi detachable coils (GDC), and the treatment of ischemic cerebrovascular
      disease such as the thrombolytic therapy for the acute embolic occlusion of the
      cerebral artery, and a percutaneous transluminal angioplasty (PTA) or a stenting
      for the stenotic lesion of the cerebral arteries. Embolization of the cerebral
      aneurysm using GDC is less invasive method compare to the standard neurosurgical
      clipping of aneurysm. So, recently it becomes one of standard methods of the
      treatment of cerebral aneurysm. Thrombolytic therapy, PTA and stenting also
      become an important treatment for the ischemic cerebrovascular disease.

PMID- 11464468
TI  - [Pathophysiology and prevention of cardiogenic brain embolism].
AB  - Cardiogenic brain embolism (CBE) accounts for approximately 20% of symptomatic
      ischemic stroke patients in Japan. Nonvalvular atrial fibrillation (NVAF) is the
      most common cause of CBE, accounting for approximately 50%. As compared to other
      ischemic stroke subtypes such as lacunar and atherothrombotic infarction, CBE is
      accompanied by more extensive infarction and more pronounced brain edema.
      Reopening of an occluded artery, that may cause hemorrhagic transformation (40%)
      or exacerbate brain edema, is frequently observed (60 to 90%). Early mortality
      and recurrence rates are high, and outcome is often poor. Patients with CBE older
      than 70 years have NVAF more frequently (76%) and their outcome is worse as
      compared to the younger CBE patients. In North American and European countries,
      warfarin with the intensity of 2.0 to 3.0 (or 4.0) is recommended for NVAF
      patients with advanced age, hypertension, history of brain infarction, or other
      high-risk features. Our prospective, randomized study, however, indicated that
      the low-intensity warfarin (INR 1.5 to 2.1) may be safer than the conventional
      intensity treatment for the secondary prevention of stroke in CBE patients with
      NVAF, especially in old ones. Prospective, randomized trials must be conducted to
      establish the optimal treatment strategy in primary prevention of stroke in
      Japanese persons with NVAF.

PMID- 11464469
TI  - [CADASIL: clinical analysis of CADASIL and CADASIL-like disorders in Japan].
AB  - To clarify the characteristics of CADASIL in Japan, we performed clinical and
      genetic investigations for six patients from 5 Japanese families diagnosed as
      CADASIL. We identified that the onset of focal neurologic deficits ranged from 38
      to 63 years old (mean 49 +/- 9.4 yrs) and the occurrence rates of main neurologic
      symptoms and signs were 1/6 for migraine, 3/6 for recurrent stroke episodes, 6/6
      for dementia, and 4/6 for pseudobulbar palsy. The marked narrowing of retinal
      arteries were observed in 3/6. The notch 3 mutations were all found in exon 4.
      Although other several families shared similar phenotype of CADASIL, there were
      no deposition of granular osmiophilic materials within the basal lamina of smooth
      muscle cells in the arterioles of biopsied muscle and no mutations in the cording
      regions of notch 3 gene. We investigated prospectively the incidence of CADASIL
      and CADASIL-like disease in Kumamoto district from 1999 to 2000. One thousand and
      thirty four patients with stroke were hospitalized in 6 hospitals which have
      stroke care unit. Among them, 7 patients fulfilled the criteria that were less
      than 60 years old, lacunar strokes and/or TIA, presence of a family history, and
      no risk factors such as hypertension, diabetes mellitus, and hyperlipidemia. One
      of seven patients was diagnosed as CADASIL by DNA analysis. It was suspected the
      incidences of CADASIL and CADASIL-like disease were not so rare in Japan.

PMID- 11464470
TI  - [Antithrombotic therapy in cerebral infarction].
AB  - Antithrombotic therapy for the acute stage of cerebral infarction consists of
      thrombolysis, anticoagulant therapy and antiplatelet therapy, and their
      indications depend on the clinicopathological type of lesion, time after onset,
      and severity of illness. Tissue plasminogen activator has been approved in the
      United States for use in cerebral infarction within 3 hours after onset. The
      usefulness of heparin as anticoagulant therapy at the acute stage of cerebral
      infarction was not proved by the International Stroke Trial due to hemorrhagic
      complication. A selective thrombin inhibitor (argatroban) is used in Japan for
      atherothrombotic cerebral infarction within 48 hours after onset. A selective
      thromboxane A2 synthetase inhibitor (sodium ozagrel) had been approved for
      cerebral thrombosis within 5 days after onset. Aspirin (160-300 mg/day) is
      effective, but slightly, in the acute stage of cerebral infarction by the
      International Stroke Trial and Chinese Acute Stroke Trial. To prevent recurrence
      of stroke in the chronic stage of cerebral infarction, antiplatelet therapy (with
      aspirin or ticlopidine) is used for atherothrombotic cerebral infarction, and
      anticoagulant therapy with warfarin for cardioembolic cerebral infarction.

PMID- 11464471
TI  - [Recent progress in diagnostic imaging of cerebrovascular diseases].
AB  - The recent development of the neuroimaging modalities has enabled early detection
      of abnormal cerebral perfusion due to arterial steno-occlusive lesions by means
      of single photon emission computed tomography (SPECT) and perfusion weighted
      images of magnetic resonance imaging (MRI), early detection of ischemic brain
      damage by means of diffusion weighted image of MRI, and lacunar infarction and
      hemorrhage by means of T 2 * weighted images. These methods are now available for
      the clinical practice. The imaging technique further visualized various
      pathological states associated with cerebrovascular disease. The fiber tracts in
      the white matter and its disruption can be evaluated by anisotropy imaging of
      MRI. Selective neuronal necrosis after mild ischemia was detected by radioactive
      tracers specifically bound to neurons. These progress may contribute to uncover
      the pathophysiology of cerebrovascular diseases and to treat the patients.

PMID- 11464472
TI  - [The advance in the research and therapeutic trials of amyotrophic lateral
      sclerosis].
AB  - The research concerning with the pathogenesis of amyotrophic lateral sclerosis
      (ALS) has been in steady progress in the last 10 years, including discovery of
      SOD mutation in familial ALS. Riluzole, by its inhibiting excitatory amino acid
      release, is the only drug, which has been demonstrated the neuroprotective
      activity in the randomised double-blind placebo-controlled clinical trials in
      patients with ALS, although many other clinical therapeutic trials for ALS
      patients has been carried out. We discussed the clinical trials being the under
      way, especially SR57746A, (1-[2-(naphth-2-yl)ethy]-4-(3-trifluoromethyl phenyl)
      1, 2, 5, 6-tetrahydro-pyridine, hydrochloride), a non-peptide compound which has
      been shown to exhibit a wide range of neurotrophic effects both in vitro and in
      vivo, and its phase II study in Japan and two kinds of phase III studies ongoing
      in the United States, Canada and Europe. We also introduced the clinical
      guideline for practice and care of ALS patients proposed by American Academy of
      Neurology, expecting to establish clinical guideline to be applicable to Japanese
      cases.

PMID- 11464473
TI  - [Recent progress in treatment for multiple sclerosis].
AB  - Multiple sclerosis (MS) is currently considered to be an autoimmune disease
      mediated by myelin antigen-specific Th 1 cells. Although the mechanism of MS
      remains to be elucidated, new disease modifying drugs have recently been
      introduced to MS treatment. Interferon-beta, copolymer 1 and intravenous
      administration of immunoglobulins have been shown to significantly reduce the
      relapse rate, progression of disease and increase of MRI lesion load in MS.
      However, as the effects of these drugs are nonspecific immunomodulation, specific
      immunomodulation therapy for MS is called for. T cell vaccination, altered
      peptide ligand and oral tolerance are possible candidates for specific immune
      therapy for MS. As in Asians there is such a distinct subtype of MS as HLA-DPB 1
      * 0501-associated opticospinal MS, it is important to look for unique immune
      therapy for opticospinal MS in future.

PMID- 11464474
TI  - [Recent advances of the treatment in metabolic disorders].
AB  - Familial amyloid polyneuropathy (FAP) and adult type (type II) citrullinemia are
      caused by metabolic disorders in liver: the vast majority of serum amyloid
      precursors (variant forms of transthyretin) in FAP are produced in liver and
      adult citrullinemia is ascribed to a deficiency of argininosuccinate synthetase
      (ASS), one of the five urea cycle enzymes in liver. Liver transplantation is,
      therefore, expected to correct the underlying metabolic abnormalities in both
      diseases. We performed partial liver transplantation using grafts from living
      donors for 13 patients with FAP and outcomes of 10 patients are satisfactory:
      polyneuritic and autonomic symptoms are gradually improving. The remaining 3
      patients, all of whom were at advanced stages of the disease, had adverse
      postoperative results, presumably because of serious dysfunctions of amyloid
      laden systemic organs. Similarly seven patients with adult citrullinemia received
      this transplantation and all recovered uneventfully. After operation plasma
      levels of ammonia and citrulline were soon normalized and five patients had
      returned to their previous social lives. Liver transplantation is a very
      promising therapy for the liver-based metabolic disorders.

PMID- 11464475
TI  - [Molecular therapy of muscular dystrophy].
AB  - Muscular dystrophy is a nosology for a group of hereditary muscle disorders
      characterized by progressive wasting and weakness of skeletal muscle, where
      degeneration of muscle fibers is detected by pathological examination. Since the
      causative gene of Duchenne muscular dystrophy (DMD), the most severe and abundant
      form of muscular dystrophy, the DMD gene, and its product dystrophin was isolated
      by positional cloning by Dr. Kunkel and his colleagues, the studies on molecular
      pathologies of muscular dystrophy has been extensively developed. The current
      therapeutic approaches of muscular dystrophy, such as DMD involves
      pharmacological suppression of the inflammatory and immure responses, which
      usually provides only modest and temporary beneficial effects. Future approaches
      depend on cell and gene therapy technology and will require different strategies,
      none of which are currently ready to enter clinical practice. These approaches
      involve the efficient, non-antigenic gene transfer for in vivo gene therapy,
      pharmacological upregulation of the synthesis of utrophin, a related protein that
      compensates for the loss of dystrophin, and myogenic stem cell transplantation.
      These approaches could be integrated each other and called as molecular therapy.

PMID- 11464476
TI  - [A dynamic neuropsychological approach].
AB  - There are at least two approaches in evaluating neuropsychological patients. One
      is to analyze negative symptoms and find a correlation between a damaged brain
      lesion and a lost function. The other is to focus on the nature of positive
      symptoms and find a principle ruling a behavioral change caused by a lesion.
      Although both approaches are equally important, I focused on the latter approach
      in this symposium. Two syndromes, i.e. forced manipulation of tools and
      hyperlexia are interpreted in terms of the rivalry between the top-down process
      of inhibition and bottom-up process of stimulus processing, resulting in the
      predominance of the latter. Two other symptoms, i.e. misperception in a case of
      associative visual agnosia and habitual behavior in a frontal damaged-dementia
      are interpreted in the same terms, but resulting in the predominance of the top
      down process. These syndromes clearly illustrate that the behavior is organized
      on the dynamic balance between the information generated internally and the one
      coming in from the environment.

PMID- 11464477
TI  - [The advantages and limitations of brain function analyses by PET].
AB  - PET has been proved to be a powerful tool for exploring the brain function. We
      discussed the advantages and limitations of PET for analyzing the brain function
      on the basis of our clinical and experimental experiences of functional imaging.
      A multimodality PET study measuring cerebral energy metabolism (CMRO2 and
      CMRglc), cerebral blood flow (CBF), oxygen extraction fraction (OEF) and
      neurotransmitter function (presynaptic and postsynaptic) opens up a closer
      insight into a precise pathophysiology of the brain dysfunction: In cerebral
      infarction, it reveals a state of "misery perfusion" in the acute stage, "luxury
      perfusion" in the intermediate stage, and proportionately decreased CBF and CMRO2
      in the chronic stage. Neurotransmitter function may identify specifically a
      neuronal subgroup of dysfunction. Owing to the low temporal resolution of PET, a
      neuronal activity may propagate transsynaptically to remote areas during the
      period of scanning, resulting in an obscured primary site of the neuronal
      activity. Uncoupling between neuronal activities and cerebral energy
      metabolism/CBF may occur under a certain state of brain pathology, particularly
      after an acute destructive lesion, according to our experimental studies.
      Neurotransmitter function may reveal the effect of drugs on the brain function,
      and may be useful for developing a new method of drug therapy for brain diseases
      in the future.

PMID- 11464478
TI  - [Evaluation of brain function: electrophysiology of the motor system].
AB  - To evaluate brain motor function, transcranial magnetic stimulation and
      supraspinal control of spinal reflexes are reviewed. Motor evoked potentials
      (MEPs) is facilitated after movement, depending on muscles (arm, hand) and
      movements (isometric, precise, repetitive, sequential), which indicates
      specialization of cortical mechanisms. EMG triphasic pattern in ballistic
      movement is delayed by magnetic stimulation, but the pattern itself is preserved.
      Ballistic and associated posture-adjusting movements are delayed by magnetic
      stimulation in the same way, and similar cortical mechanisms appear to be
      included. Patients with motor neglect, normal MEPs and remarkably prolonged
      silent period show inability to initiate movement for several seconds after
      magnetic stimulation, and strong and long-lasting intracortical inhibition are
      observed. Motor neglect can be produced by strong inhibitory inputs to the motor
      cortex. Neural plasticity is studied in patients with brain and peripheral
      lesions; ipsilateral MEPs, enlargement of muscle representation in the cortex,
      and contribution of descending pathways other than corticospinal tract are
      reported. Central control of spinal reflex activities is also important in motor
      control. Reflex circuits contribute to reciprocal inhibition and to selective
      contraction, or function as an attenuator of activity of the motoneurone pool.
      Neural plasticity after daily exercise is reported also at the segmental level.

PMID- 11464479
TI  - [Functional MRI-motor reorganization].
AB  - With rapid advancement of non-invasive imaging technologies, it is now possible
      to perform a detailed assessment of brain functional reorganization in humans.
      Studies in hemiparesis patients due to corticospinal tract impairment strongly
      suggest an important role of ipsilateral cortex and supplemental motor cortices
      in functional reorganization of the motor system. Studies in patients with
      peripheral nerve disease indicate that central nervous system reorganization
      indeed occurs based on peripheral motor dysfunction. Data on cerebellar
      reorganization indicate a potential role of the reticular formation in motor
      functional reorganization.

PMID- 11464480
TI  - [Segawa's disease].
AB  - Segawa's disease (dopa-responsive dystonia) is caused by a genetic mutation in
      the gene for GTP cyclohydrolase I, a rate-limiting enzyme for the biosynthesis of
      tetrahydrobiopterin. Although the causative gene was identified, many issues
      remain to be addressed in this disease. In this short article, we have described
      and discussed the relevance of measurement of GTP cyclohydrolase I activity in
      phytohemagglutinin-stimulated mononuclear blood cells in patients with Segawa's
      disease. Although the enzyme activity in immune cells may not reflect the
      activity in the brain, we can evaluate the maximum ability in the induction of
      GTP cyclohydrolase I in the cell from this method. Under normal conditions
      without any stimulant, some compensatory mechanism(s) may attenuate the
      difference in the enzyme activity between patients and normal individuals. Since
      one allele is inactivated in patients with Segawa's disease, we can distinguish
      the patients from normal individuals without examining their gene-defect. Because
      we cannot identify a mutation in the coding region and the exon-intron junction
      of GTP cyclohydrolase I in about half of patients with Segawa's disease, this
      biochemical assay has great value in diagnosis of the disease.

PMID- 11464481
TI  - [Dentatorubral-pallidoluysian atrophy (DRPLA)--discovery of the disease, DRPLA
      gene and the pathophysiology].
AB  - The clinical entity of dentatorubral-pallidoluysian atrophy (DRPLA) was
      discovered and established in Japan. The characteristic clinical genetic features
      of DRPLA including prominent anticipation prompted us to search the genes
      carrying CAG repeats as the candidate genes for DRPLA. Based on this approach,
      the DRPLA gene was discovered by two independent Japanese groups in 1994. Given
      that DRPLA is caused by expansion of CAG repeats, the molecular mechanisms of the
      anticipation and the broad clinical presentations of DRPLA depending on the age
      at onset are clearly understood as a function of the size and the instability of
      the CAG repeats. Recent studies have suggested that mutant proteins with expanded
      polyglutamine stretches have "gain-of-toxic" functions to neuronal cells. The
      molecular mechanisms of the "toxic" functions, however, have not been identified.
      Based on the recent findings that nuclear transport of the mutant proteins
      carrying expanded polyglutamine stretches is important in the pathogenesis, we
      screened nuclear proteins which bind to expanded polyglutamine stretches. We
      found that expanded polyglutamine stretches bind to TAFII130, a TATA-binding
      protein-associated factor, and interfere with CREB-dependent transcriptional
      activation. Since CREB-dependent transcriptional activation plays essential roles
      in neuronal survival and plasticity, such interference is expected to lead to
      neuronal dysfunction.

PMID- 11464482
TI  - [Aceruloplasminemia].
AB  - Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains greater
      than 95% of the copper present in human plasma. It is synthesized mainly in the
      liver. Aceruloplasminemia is an autosomal recessive disorder affecting iron
      metabolism, originally called familial apoceruloplasmin deficiency, which
      manifests late-onset blepharospasm and retinal degeneration. Subsequent
      investigations have found patients with late adult onset of ataxia and diabetes
      mellitus. Our patients have also shown diabetes. Clinically, aceruloplasminemia
      is a triad consisting of neurologic disease, retinal degeneration, and diabetes.
      This disease is characterized by mutations in the ceruloplasmin gene and iron
      accumulation in the retina and basal ganglia as well as in parenchymal tissues
      caused by a complete deficiency of ceruloplasmin ferroxidase activity. The
      neurological symptoms in affected patients include involuntary movements, ataxia,
      and dementia reflecting the sites of iron deposition detected by MRI as well as
      the regions of neurodegeneration observed at autopsy. Consistent with this
      observation, ceruloplasmin gene expression is detected in the retina and basal
      ganglia revealing that this protein is essential for iron homeostasis neuron
      survival in the central nervous system. The unique involvement of the central
      nervous system distinguishes aceruloplasminemia from other inherited and acquired
      iron storage disorders.

PMID- 11464483
TI  - [Autosomal recessive juvenile parkinsonism: its pathogenesis is involved in the
      ubiquitin-proteasome pathway].
AB  - The contribution of genetic factors in the pathogenesis of PD is supported by the
      demonstration of the high concordance in twins studies using PET, the increased
      risk among relatives of PD patients in case control and family studies, and the
      existence of familial PD and parkinsonism by single gene defect. Recently, two
      genes such as alpha-synuclein and parkin have been identified. alpha-Synuclein is
      involved in a rare dominant form of familial PD with dopa responsive parkinsonian
      features and Lewy body positive pathology. In contrast, parkin is responsible for
      autosomal recessive form (AR-JP) of early onset PD with Lewy body-negative
      pathology. To date, variable mutations such as deletions or point mutations have
      been reported in AR-JP patients from world wide. In addition, the localization of
      parkin indicates parkin may are involved in the axonal transport system. More
      recently, we have found that parkin interacts with ubiquitin-conjugating enzyme,
      UbcH 7, and is functionally linked to the ubiquitin-proteasome pathway as a
      ubiquitin ligase. These findings fit the characteristics of lack of Lewy bodies
      which are cytoplasmic inclusions considered a pathological hallmark. Our findings
      should enhance the exploration of the mechanisms of neuronal death in PD as well
      as other neurodegenerative disorders of which variable inclusion bodies are
      observed.

PMID- 11464484
TI  - [Fukuyama-type congenital muscular dystrophy].
AB  - Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by congenital
      muscular dystrophy in combination with cortical dysgenesis and ocular
      abnormality. We identified on chromosome 9 q31 the gene for FCMD, which encodes a
      novel 461-amino-acid protein (fukutin). Most FCMD-bearing chromosomes have been
      derived from a single ancestral founder, whose mutation consisted of a 3-kb
      retrotransposal insertion in the 3' non-coding region of the fukutin gene. Some
      point mutations causing premature termination were found. Amino acid sequence and
      transfection experiments suggest that fukutin may be an extracellular protein.
      Pathological study on the brain of the FCMD fetuses revealed that the glia
      limitans and basement-membrane complex had frequent breaks. Because of this,
      developing neurons were shown to overmigrate in the cerebrum. Electron microscopy
      of the skeletal muscle in FCMD showed that the basal lamina has a disrupted
      appearance. Thus, a structural alteration of the basal lamina appears to play a
      key role in the pathophysiology of FCMD. The spectrum of clinical variability of
      FCMD is much wider than recognized previously. Point mutations have been seen to
      render the FCMD phenotype rather severe. FCMD could give rise to only in the
      Japanese who have a milder retrotransposon mutation.

PMID- 11464485
TI  - [Current status and needs of the department of neurology as a specialized
      department of a general hospital].
AB  - In this report, I have summarized the current situation surrounding diagnosis,
      treatment and related needs in the department of neurology in relation to
      postgraduate neurology training considered from the standpoint of a specialized
      department within a general hospital. This summary is based on the responses to a
      questionnaire that was sent to the persons in charge of education and training at
      180 institutions affiliated with the Japanese Society of Neurology and 478
      education and training institutions among Japanese city hospitals, excluding
      university hospitals and special research institutions. Replies were received
      from 305 hospitals, amounting to a response rate of 63.8%. The number of doctors
      working in the department of neurology was found to be low at 2 in 84 hospitals
      and 3 in 65 hospitals. The majority of neurologists at general hospitals are
      fully engaged in examining outpatients as well as inpatients, and they do not
      have adequate time for research, education and training and participation in the
      activities of academic associations. Of the 10 items cited in the questionnaire
      relating to the types of postgraduate neurology training desired by neurologists
      employed in general hospitals, the most common selections in order of decreasing
      frequency were improvement in the capacity to manage common disorders (such as
      headache, dizziness, numbness, etc.) diagnosed in the outpatient clinic,
      improvement in the capacity to diagnose the acute phase of cerebral apoplexy,
      further education about EEG (electroencephalogram) and EMG (electromyogram), and
      medical ethical issues such as informed consent. The views about postgraduate
      neurological education and training described in detail in writing by the
      respondents were as follows. 1) Neurologists required by a city general hospital
      Numerous respondents commented that the capacity to diagnose medical neurological
      diseases associated with internal (systemic) medical disorders is needed since
      there are remarkably few doctors in general hospitals whose interest is confined
      only to neurological diseases ranging from rare to common complaints. In
      contrast, neurologists whose knowledge and training derives from a wide clinical
      base of internal medicine are in great demand. 2) Points of disparity between
      postgraduate neurology training in a university hospital and neurologists
      required by a city general hospital In addition, many respondents expressed the
      view that under the medical school system, neuroscience and research are given a
      higher priority than the cultivation of clinical medical skills and although
      there may be keen academic interest in the clinical diagnosis and treatment of
      rare diseases, there is not necessarily the same level of keen interest in common
      diseases, hence the universities may be educating researchers effectively, but
      are not necessarily producing capable clinicians. 3) Measures that should be
      taken to address this difference in postgraduate neurology training between
      university and city general hospitals The university hospital is separated into
      research and clinical groups and the time has now come for a system of management
      under which a professor leads the research group and another professor leads the
      clinical group. There should be a clear-cut clarification of the responsible
      roles of university and city general hospitals in the postgraduate education and
      training of neurologists. Furthermore, the professional staff and facilities of
      general hospitals that are affiliated with universities should be upgraded and
      expanded to enable them to serve more effectively as sites of clinical education
      and training. The position and status of neurologists at city general hospitals
      should be raised to the same level as that of university professors and
      institutions affiliated with the Japanese Society of Neurology.

PMID- 11464486
TI  - [Current status and need for neurological practices from regional medical
      institutions].
AB  - We studied the current status of, and need for, neurological practices from
      regional medical institutions, including in-home services. These institutions
      classify patients with neurological diseases into three categories:
      cerebrovascular disease, intractable diseases, and other diseases with
      neurological symptoms. As acute and chronic neurological diseases run their
      course, patients require appropriate care, including diagnosis, treatment,
      rehabilitation, and in-home medical care. Rehabilitation is essential for
      patients with intractable or progressive disease because it helps to prevent
      progression, enhances mental health, and encourages the use of abilities that are
      unaffected by disease. As neurologists, we must consider how we can have a
      positive impact on the patient, the hospital, and the community. In Japan, the
      majority of patients who receive in-home medical care have neurological
      disorders, such as cerebrovascular disease or other intractable diseases. We have
      provided in-home support to 18 patients with amyotrophic lateral sclerosis who
      use ventilators. This year, a long-term care insurance system was instituted in
      Japan. Now, a support system needs to be established to provide community-based
      medical care, health care, and welfare services. As our population ages, we
      believe neurologists will play an increasingly important role in this support
      system.

PMID- 11464487
TI  - [Proposal of postgraduate training program in neurology].
AB  - In order to improve the postgraduate training in neurology in Japan, practical
      program is proposed. It consists of 5 years. The first 2 years include internal
      medicine for 16 months, pediatrics for 2 months, neurosurgery for 2 months,
      emergency medicine for 2 months, and anesthesiology for 2 months. The next 3
      years include neurology training in the ward and out-patient clinic in the
      University Hospital for one year followed by another year of neurology ward
      training at the affiliated hospital where they are exposed to see more acute
      neurological cases. In addition to these clinical training, they will study basic
      neurological sciences in neuroanatomy, and neurophysiology in the evening in the
      form of small group seminars and they are assigned to read EEG every week and
      attend EEG reading sessions. EMG, muscle biopsy, and sural nerve biopsy will be
      done under supervision when they are in charge of such cases who require those
      examinations. The last year program includes neurological consultation from the
      other departments, out-patient clinic, setting up neurological conferences, and
      elective course for 3 months. It is recommended that Japanese Neurological
      Society informs us several institutes where they can offer pediatric neurology
      training, and neuropathology training in several districts in Japan, since they
      have difficulty in getting training in these two specialties in many Japanese
      hospitals.

PMID- 11464488
TI  - [Postgraduate training program in neurology--in university and the affiliated
      hospital].

PMID- 11464489
TI  - [Influence of histologic type on prognosis of patients undergoing curative
      intervention for gastric adenocarcinoma. Italian multicenter study].
AB  - BACKGROUND: The prognostic significance of the histological type in gastric
      cancer is still debated. The correlation between intestinal-diffuse type and
      tumor recurrence was investigated in a prospective multicentric study which
      collects the cases from three surgical Departments of Italy. PATIENTS AND
      METHODS: Four-hundred and twelve patients who underwent a potentially curative
      resection between 1988 and 1995 were considered; 273 cases were classified as
      intestinal type (group A), and 139 cases as diffuse type (group B). Mixed cases
      were excluded from the study. All patients were included in a complete follow-up
      program for the early diagnosis of recurrence. Clinical, histopathological and
      surgical factors were examined for their influence on tumor recurrence by
      univariate and multivariate analysis. RESULTS: Recurrence rate was 41.4% in
      intestinal type, and 65.5% in diffuse type cases (p < 0.0001). In group A,
      multivariate analysis identified nodal status (p < 0.0001), depth of invasion (p
      < 0.005), lymph node dissection (D1 vs. D2-D4, p < 0.01), advanced age (p < 0.01)
      and male sex (p < 0.05) as significant prognostic factors. In group B, depth of
      invasion (p < 0.0005), lymph node dissection (p < 0.005), tumor size (p < 0.01)
      and nodal status (p < 0.05) resulted as significant variables; no preventive
      effect on tumor recurrence was found for D2 vs. D1 lymphadenectomy. Multivariate
      analysis performed on the totality of the cases demonstrated diffuse type as an
      independent predictor of poor prognosis (relative risk: 1.67, p < 0.001).
      CONCLUSIONS: Diffuse type of gastric cancer is an independent risk factor for
      tumor recurrence as compared with intestinal type; clinical and pathological
      variables play a different role as prognostic factors in the two histotypes.

PMID- 11464490
TI  - [Principles of oncologic radicality in the surgical treatment of gastric
      carcinoma].
AB  - To date the basic guidelines in surgical oncology of the stomach may be
      summarized in the correct definition of "R0" exeresis (curative operation), but
      there is still much debate on which should practically be the extension of the
      gastric resection and which the kind of lymphatic dissection in order to fulfill
      all the criteria for a correct definition of "curative surgery". As regards the T
      factor, almost all Authors agree on the fact the a correct R0 gastric resection
      must include a tumor-free distal margin at least 6 cm from the superior edge of
      the neoplasm; a safe distal margin should be at least at 1 cm. below the pylorus.
      Provided that these principles are thoroughly observed, there is no oncologic
      advantage in performing a total gastrectomy instead of a sub-total gastric
      resection. Differently, as regards the N factor, there is no agreement on which
      kind of lymph nodal dissection shoul be routinely adopted: published reports on
      this subject are somewhat controversial and also whereas a systematic extended
      lymphadenectomy showed a possible statistical benefit in long term-survival,
      unacceptable morbidity rates discourage a diffuse application of extended
      lymphatic dissection out of dedicated; institutions. Anyhow, at the moment it is
      almost universally accepted that a minimum of 25 removed nodes are necessary for
      a correct and comparable staging of gastric cancer. At last, literature data do
      not support the routine use of splenectomy, with the only exception of those
      cases with documented lymph nodal enlargement at the splenic hilum.

PMID- 11464491
TI  - Early gastric cancer: endoscopic mucosal resection.
AB  - In Japan, endoscopic mucosal resection (EMR) is now accepted as a treatment
      option for cases of early gastric cancer (EGC) with minimum probability of
      associated lymph node metastasis. In National Cancer Center Hospital (NCCH), EMR
      is currently applied to patients with early cancers up to 30 mm diameter that
      were of intestinal type, and were superficially elevated and/or depressed (Type
      I, IIa and IIc) but without ulceration or definite signs of submucosal invasion.
      Four hundred seventy nine lesions of EGC in 449 patients were treated by EMR from
      1987 through 1998. Submucosal invasion was found on subsequent pathologic
      examination in 74 lesions, and surgery was recommended. Sixty nine percent of
      intramucosal cancer was resected with a clear margin, which was therefore judged
      to be a "complete resection". Local recurrence in the stomach occurred in 2% (5
      lesions) with complete resection and in 17% (18 lesions) without complete
      resection treated conservatively or endoscopically, and all were subsequently
      treated with curative intent. There were no gastric cancer-related deaths for a
      median follow-up period of 38 months (3-120 months). Bleeding and perforation
      were two major complications in EMR, but there were no treatment-related deaths.
      We believe that EMR allows us to perform less-invasive treatment without
      sacrificing the possibility of cure. We hope to promote its use around the world.

PMID- 11464492
TI  - ["Update on gastric carcinoma"].

PMID- 11464493
TI  - Staging laparoscopy for gastric cancer.
AB  - The growing role of multimodal treatment plans for advanced gastric cancer has
      contributed to the development of more accurate preoperative staging strategies.
      The high diagnostic efficacy of video-laparoscopy as regards the M factor has
      been reported by many; preoperative laparoscopy therefore permits to avoid
      unhelpful surgical exploration in case of peritoneal dissemination of tumor or
      liver metastases undetected by conventional staging. At Memorial Sloan Kattering
      Cancer Center preoperative staging laparoscopy is currently included in the
      diagnostic algorithm for gastric cancer. Data from a consecutive series of 103
      patients demonstrated metastatic disease in 24 patients (37%) who were considered
      to have localized cancer by computed tomography (CT) or endoscopic
      ultrasonography (EUS), with an accuracy of 94% with respect to the M factor.
      These patients did not require open surgery. Laparoscopic washings were obtained
      from 127 patients with gastric cancer and a positive correlation between the
      extent of disease and prevalence of positive cytology was noted (T1/T2: 0%,
      T3/T4: 10%, M+: 59%). Our experience suggests that laparoscopy has added value in
      staging patients with gastric carcinoma. It appears to be a safe and effective
      staging modality, avoiding unnecessary explorations and providing new means of
      directing appropriate treatment strategy.

PMID- 11464494
TI  - [Role of lymphadenectomy in gastric carcinoma].
AB  - Controversy still surrounds the value of extensive regional lymphnode dissection
      in the treatment of gastric cancer. The aim of the present paper is to give this
      topic a contribution through the review of the literature and the analysis of
      personal results.

PMID- 11464495
TI  - [Neoadjuvant chemotherapy in gastric carcinoma].
AB  - A complete surgical resection currently represents the only curative treatment
      option for gastric carcinoma, but as regards locally advanced cancer the
      possibility of local or distant recurrence remains extremely high even following
      a R0 resection. As far as T3-4/N+ tumors are concerned, unsatisfying results of
      surgery alone have stressed the need for multimodal treatments: in the recent
      past adjuvant chemotherapy has represented a common complementary treatment for
      locally advanced gastric cancer, but conclusive results of most randomized trials
      did not show a significant impact on long term survival. Literature review shows
      a growing trend throughout the 90's towards the adoption of a preoperative
      chemotherapy, initially evaluated as a form of "salvage" palliative treatment for
      unresectable patients. To date a number of phase II study suggests the efficacy
      of neo-adjuvant treatment administered to resectable patients with the purpose of
      inducing tumor downstaging, increasing the rate of R0 resections and controlling
      recurrencies. From March 1996 the Authors have started a controlled study on neo
      adjuvant therapy for locally advanced gastric cancer. Accurate staging and
      patients selection were based upon immediately preoperative laparoscopy. In this
      ongoing study, patients are administered two preoperative cycles of EEP
      chemotherapy (Etoposide, Epirubicin, cis-Platin). Preliminary data have been
      evaluated on the first 15 cases. Grade I myelosuppression has been observed in
      12/15 cases and grade II/III in 3/15 cases; 1 patient died by septic
      complications. Restaging has not shown progression of the disease in 13/14 cases;
      a macroscopic response was evidenced in 7/14 patients; 14/14 patients could
      undergo a successful D2 surgical resection following neo-adjuvant therapy.
      Pathological staging confirmed tumor downstaging in 7 out of 14 cases; 12/14
      patients in this group (85.7%) could benefit a R0 resection. These preliminary
      data encourage us to proceed in our prospective investigation.

PMID- 11464496
TI  - [Helicobacter pylori and gastric carcinoma].
AB  - Among the suspected bacterial causes of cancer, H. pylori is the agent more
      consistently linked to malignancy. After its discovery in 1983 and the later
      confirmation as the leading cause of chronic gastritis, several studies were
      performed to prove an association between H. pylori infection and gastric
      carcinoma. The epidemiological data have been so strong that in 1994 the
      International Association for Research on Cancer stated that "there was
      sufficient evidence" to classify H. pylori as a group I carcinogen in humans.
      However, the exact mechanisms underlying the link between H. pylori infection and
      gastric carcinoma remain still to be elucidated. The natural history of H. pylori
      infection shows that, although roughly half of the world's human population bears
      the organism, only a minority of individuals develop clinically important
      outcomes (e.g. peptic ulcer, lymphoproliferative diseases, atrophic gastritis and
      gastric carcinoma): host's genetic make-up, duration of infection, diet and
      differences between H. pylori strains have been proposed as factors potentially
      able to influence the outcomes in different individuals. The damaging agents by
      which H. pylori could promote gastric carcinogenesis are produced either by the
      organism or as a consequence of the host inflammatory response to the infection.
      Gastric mucosal chronic damage may, therefore, lead to changes in the pattern of
      epithelial cell kinetic (increase in cell proliferation and induction of
      apoptosis) in gastric glands which may induce DNA injury with irreversible
      genetic lesions. Finally, a direct association between H. pylori infection and
      the induction of gastric carcinoma has been recently demonstrated in an animal
      model, giving further credence to the role of this organism in gastric
      carcinogenesis.

PMID- 11464497
TI  - [Adjuvant chemotherapy in gastric carcinoma].
AB  - The adjuvant chemotherapy (A.C.) is considered as a complementary treatment in
      patients who underwent radical surgery for gastric cancer, with complete removal
      of the tumor and absence of macroscopically detectable metastasis. This treatment
      is generally started within 4-6 weeks after the operation. The indication to A.C.
      is related practically only to the stage of the disease, due to the fact that no
      other prognostic factors of an increased risk of relapse have been detected. Two
      metanalysis have been recently published by Earle (1998) and Floriani (1998);
      both the two have recognized a possible effective role of the CA for Gastric
      Cancer. Naturally these "impressions" of efficacy documented by these two
      metanalysis should be confirmed through new trials with larger recruitment. In
      these new trials the new generation schedules (weekly PELF, ECF plus 5-FU), which
      showed an increased response for advanced disease, should be administered.

PMID- 11464498
TI  - [Our experience regarding biologically inactive gastroenteropancreatic
      neuroendocrine tumors].
AB  - The Authors present 9 cases of gastro-enteropancreatic neuro-endocrine
      biologically inactive tumors. In 5 cases the tumor site was appendicular. In 4
      patients an appendectomy was performed, in one patient a right hemicolectomy and
      the patients after a period of 3-9 years are well and disease free. In a patient
      with a gastric carcinoid and a single hepatic metastasis a total gastrectomy with
      an hepatic metastasectomy were performed but the patient died 16 months
      thereafter. In a case localized to the right colon with a single hepatic
      metastasis a right hemicolectomy was performed with a metastasectomy but the
      patient died after 12 months. In a case localized to an ileal loop a segmental
      resection was performed followed by a medical therapy with octreotide and the
      patient is well and disease free after 3 years. In a case localized to the
      pancreas with widespread lymphatic metastasis it was performed a simple biliary
      diversion (coledocho-duodenostomy) followed by medical therapy with octreotide.
      Surprisingly after 4 years the patient is alive and a TC control shows a decrease
      of the pancreatic tumor and of the lympho glandular tumefactions.

PMID- 11464499
TI  - [Gastrin and colorectal cancer].
AB  - The aim of present study was to assess preoperative/postoperative serum gastrin
      level variations and their prognostic value in patients with colo-rectal cancer.
      Levels have been evaluated in 66 subjects undergoing colo-rectal cancer surgery,
      with curative intent, from may 1990 to february 1994. Preoperative gastrin
      analysis was performed on peripheral blood samples in starred patient just prior
      surgery. Postoperative gastrin assessment was performed 7 day after surgery in
      starred patients as well. Follow-up ranged from 5 to 8 years. No association
      between preoperative gastrin levels and tumor site, stage or grading was
      observed. No significant variation of preoperative gastrin levels (p > 0.05) was
      ascertained postoperatively neither in the whole patient series nor after
      correction for tumor stage. Postoperative levels were therefore not affected by
      surgical removal of cancer. Neither preoperative nor postoperative serum gastrin
      levels influenced significantly the 5-year survival. In our experience, with the
      limitation of a small series assessment, serum gastrin level do not seem to have
      any prognostic value in colo-rectal cancer.

PMID- 11464500
TI  - [Endoscopic diagnosis and treatment of juvenile solitary polyps, in the light of
      the unusual but proven neoplastic potential].
AB  - For many years a neoplastic potentiality of the juvenile polyps has been denied.
      The authors performed a critical review of the international literature about the
      neoplastic transformation of the juvenile polyps. Each examined case had to
      respect three conditions: 1) exhaustive hystological findings certifying a clear
      neoplastic degeneration of a juvenile polyp; 2) clear evidence of single juvenile
      polyposis (< 5), presence in the colon and rectum only and absence of
      familiarity; 3) reliable diagnostic practice (endoscopic and/or hystological
      evidence). During the review we collected 271 cases of juvenile polyposis
      observed in 12 countries, 97 of which (35.79%) showed neoplastic transformation,
      adenomatous type in 50 (18.45%) and carcinomatous type in 47 (17.34%), and 13
      cases of neoplastic degeneration of single juvenile polyps. The review shows
      clearly and strongly that the risk of cancer in the juvenile polyposis can reach
      the risk of the adenomatous polyposis. The neoplastic degeneration exists in the
      single juvenile polyps even if in a lower degree.

PMID- 11464501
TI  - [Sigma volvulus: diagnostic and therapeutic features (considerations on 10
      cases)].
AB  - BACKGROUND: Sigmoid volvulus is associated with a high mortality because affects
      elderly patients who often have severe comorbid conditions that increase their
      surgical risk. OBJECTIVES: The aim of this study was to evaluate the most common
      procedures of diagnosis and treatments to obtain better results. METHODS: The
      clinical presentation, diagnosis and treatment of 10 consecutive patients with
      sigmoid volvulus are reviewed. Ages ranged from 30 to 93 years. Endoscopic
      decompression was tried in 6 and was successful in 3 cases. Seven patients had
      emergency surgery: surgical procedures were resection in 1 case and distortion
      with sigmoidopexy in 6; two patients had elective surgery after endoscopic
      decompression: surgical procedure was resection. RESULTS: All patients had
      abdominal pain. Other symptoms were constant only in the half of the cases.
      Significant was the correlation between leucocytosis and bowel ischaemia. Plain
      abdominal radiographs was not specific while sigmoidoscopy was diagnostic in all
      the cases. Two patients died: one after non operative reduction and another after
      emergency derotation and sigmoidopexy (operative mortality: 14%). The only
      complication was an anastomotic fistula. There were no recurrences at the time of
      follow-up (1-9 years after operation). CONCLUSION: Sigmoid volvulus is difficult
      to diagnose preoperatively and is associated with a high mortality. It may be
      diagnosed and treated by sigmoidoscopy followed by elective surgery. The
      treatment of choice is resection but good choice results can be obtained also
      with derotation and sigmoidopexy.

PMID- 11464502
TI  - [Multifocal gastric carcinoid associated with chronic type A atrophic gastritis.
      Analysis of 2 clinical cases].
AB  - Gastric carcinoid is a rare disease, representing less than 1% of gastric tumours
      and 11-41% of all gastrointestinal carcinoids. The recent Solcia's classification
      distinguishes three subtypes of these neoplasms, which show specific clinical and
      pathological features. Type one arises in patients with chronic atrophic
      gastritis (CGA), achlorhydria, hypergastrinemia and consequent enterochromaffin
      like cell hyperplasia and dysplasia. Type two is related to Zollinger Ellison
      syndrome and type three represents the sporadic kind. We report two cases of
      multifocal gastric carcinoid associated to CGA, one of them with pernicious
      anemia. Both patients had aspecific abdominal symptoms; the diagnosis was
      suspected by upper endoscopy and confirmed by histological examination. Patients
      were submitted to total gastrectomy. They are still alive six years after
      surgery, without signs or symptoms of recurrences. Treatment of these tumours is
      controversial, because of their uncertain biological and clinical behaviour. Some
      Authors propose a conservative strategy (only endoscopic surveillance or
      removal); others stress importance of surgery (antrectomy or gastric resection).
      We discuss and underline the role of surgical therapy and the relevance of
      radical approach.

PMID- 11464503
TI  - [Pancreatic cystic metastasis from pulmonary carcinoma. Report of a case].
AB  - We report the case of a patients with a metachronous cystic pancreatic metastasis
      from an undifferentiated large cell lung carcinoma two years after the primary
      tumor had been surgically removed. Clinically, he presented with epigastric pain,
      fever, weakness and anorexia. The patient was operated and a palliative
      cystogastrostomy was performed after an intraoperative biopsy had been informed
      as positive for carcinoma. Six months later the patient died. Pancreatic
      metastases from lung carcinoma are found in approximately 7-9% of patients
      deceased of this neoplasm. Clinical and radiological findings simulate primary
      pancreatic tumors, being epigastric pain, jaundice and upper digestive bleeding
      the most frequent symptoms. They represent stages of advanced systemic
      disseminated tumoral disease, and because of this reason total or partial
      surgical curative resections will only be performed in a few cases of patients
      with isolated metastasis, criteria of resectability and without evidence of
      extended disease to other organs or systems. In the most of the cases, the
      treatment will only be palliative, even medical or surgical.

PMID- 11464504
TI  - Production of shotgun libraries using random amplification.
AB  - In the following report, thermal cycling coupled with random 10-mers as primers
      was used to construct randomly amplified shotgun libraries (RASLs). This approach
      allowed shotgun libraries to be constructed from nanogram quantities of input
      DNA. RASLs contained inserts from throughout a target genome in an unbiased
      fashion and did not appear to contain chimeric sequences. This protocol should be
      useful for shotgun sequencing the genomes of unculturable organisms and rapidly
      producing shotgun libraries from cosmids, fosmids, yeast artificial chromosomes
      (YACs), and bacterial artificial chromosomes (BACs).

PMID- 11464505
TI  - Analysis of ubiquitination in vivo using a transgenic mouse model.
AB  - The primary pathway for the proteolytic destruction of cellular proteins is
      through ubiquitin-mediated targeting to the proteasome. This pathway is pivotal
      not only in the elimination of damaged or misfolded proteins but also in the
      temporal, developmental, or signal-mediated destruction of normal cellular
      substrates. The list of known substrates of the ubiquitin/proteasome pathway is
      long, but most substrates have been identified in yeast or, more recently, in
      cultured mammalian cells. It is likely that many mammalian substrates with
      developmental or disease relevance have yet to be identified because their
      ubiquitination occurs in tissue or organ systems that cannot be adequately
      modeled in vitro. We have developed a transgenic mouse model that will allow the
      isolation and identification of these substrates. The human UbC promoter was used
      to drive expression of a hexahistidine-tagged version of human ubiquitin in a
      variety of mouse tissues from early embryonic stages, as assessed by a green
      fluorescent protein marker. Cleavage of the fusion protein by endogenous enzymes
      produced epitope-tagged ubiquitin that was detected both in monomeric form and
      conjugated to cellular proteins. This mouse model should facilitate in the
      analysis of normal and disease-related ubiquitination events in vivo.

PMID- 11464506
TI  - Quantitative real-time PCR assay for determining transgene copy number in
      transformed plants.
AB  - The development of transgenic events can be limited by many factors. These
      include expression levels, insert stability and inheritance, and the
      identification of simple insertion events. All of the factors can be related to
      the copy number of the transgene. Traditionally, copy number has been determined
      by laborious blotting techniques. We have developed an alternative approach that
      utilizes the fluorogenic 5' nuclease (TaqMan) assay to quantitatively determine
      transgene copy level in plants. Using this assay, hundreds of samples can be
      analyzed per day in contrast to the low throughput encountered with traditional
      methods. To develop the TaqMan copy number assay, we chose to utilize our highly
      efficient Agrobacterium-mediated transformation system of maize. This
      transformation procedure generates predominantly low copy number insertion
      events, which simplified assay development. We have also successful applied this
      assay to other crops and transformation systems.

PMID- 11464507
TI  - Isolation of genomic DNA from blood using a novel filter-based DNA purification
      technology.
AB  - A novel DNA purification technology is described that enables the purification of
      pure dsDNA from blood. When compared to existing DNA purification methods, the
      Whatman BioScience Purification System (WBPS) offers a fast and convenient way to
      recover high yields of DNA. WBPS is based on a unique filter system that entraps
      DNA within a matrix. This allows the process to be performed in a single
      unidirectional reaction vessel, reducing user interaction and multiple
      centrifugation steps.

PMID- 11464508
TI  - Detection of fluorescence dye-labeled proteins in 2-D gels using an Arthur 1442
      Multiwavelength Fluoroimager.
AB  - Labeling of proteins with SYPRO Orange, SYPRO Red, and SYPRO Ruby after 2-D
      polyacrylamide gel electrophoresis (PAGE) using plastic-backed immobilized pH
      gradient (IPG) strips and precast SDS polyacrylamide gels was tested. Protein
      spots were detected using an Arthur 1442 Multiwavelength Fluoroimager. The
      labeling methods described allow detection of proteins both after isoelectric
      focusing (IEF) and PAGE with a sensitivity higher than or comparable to standard
      silver staining methods. In addition to the post-labeling methods mentioned
      above, pre-labeling with the cysteine-specific fluorophore monobromobimane before
      2-D PAGE is a sensitive, fast, and cost-effective alternative to existing
      staining protocols.

PMID- 11464509
TI  - Proteomics--structure and function.

PMID- 11464510
TI  - Making cool drugs hot: isothermal titration calorimetry as a tool to study
      binding energetics.
AB  - Characterization of the thermodynamics of binding interactions is important in
      improving our understanding of bimolecular recognition and forms an essential
      part of the rational drug design process. Isothermal titration calorimetry (ITC)
      is rapidly becoming established as the method of choice for undertaking such
      studies. The power of ITC lies in its unique ability to measure binding reactions
      by the detection of the heat change during the binding interaction. Since heat
      changes occur during many physicochemical processes, ITC has a broad application,
      ranging from chemical and biochemical binding studies to more complex processes
      involving enthalpy changes, such as enzyme kinetics. Several features of ITC have
      facilitated its preferential use compared to other techniques that estimate
      affinity. It is a sensitive, rapid, and direct method with no requirement for
      chemical modification or immobilization. It is the only technique that directly
      measures enthalpy of binding and so eliminates the need for van't Hoff analysis,
      which can be time consuming and prone to uncertainty in parameter values.
      Although ITC has facilitated the measurement of the thermodynamics governing
      binding reactions, interpretation of these parameters in structural terms is
      still a major challenge.

PMID- 11464511
TI  - Array-based ELISAs for high-throughput analysis of human cytokines.
AB  - In this report, we describe the development of a mini-array system suitable for
      high-throughput quantification of proteins. This mini-array is a multiplexed,
      sandwich-type ELISA that measures the concentration of seven different human
      cytokines--TNF-alpha, IFN alpha, IFN gamma, IL-1 alpha, IL-1 beta, IL-6, and IL
      10--from a single sample in each well of a 96-well plate. The mini-array is
      produced by spotting monoclonal antibodies (mAbs) in a 3 x 3 pattern in the
      bottom of the wells of 96-well polystyrene plates. Cytokines that are captured by
      the arrayed mAbs are detected by using biotinylated mAbs, followed by the
      addition of a streptavidin-horseradish peroxidase (HRP) conjugate and a
      chemiluminescent substrate. The light produced from the HRP-catalyzed oxidation
      of the substrate is measured at each spot in the array by imaging the entire
      plate with a commercially available CCD camera. Here, we demonstrate that these
      96-well-plate format mini-arrays have performance characteristics that make them
      suitable for the high-throughput screening of anti-inflammatory compounds.

PMID- 11464512
TI  - Conditional gene expression in human intracranial xenograft tumors.
AB  - In an initial effort to determine the effect of expressing potentially
      therapeutic gene products on the growth properties of glioma tumor xenografts, we
      describe the development of cell lines that can conditionally express beta
      galactosidase (beta-gal). To achieve this, we generated stable cell lines that
      express the modified tetracycline repressor molecule (rtTA) and the beta-gal gene
      under control of tetracycline-responsive cis-elements. The resulting cell lines
      express functional beta-gal following treatment with the tetracycline analog
      doxycyclin (Dox). These cells were then used to form intracranial tumors after
      injection into the brain using an implantable guide-screw system. The xenografts
      were found to express beta-gal when the animals were fed drinking water
      containing Dox. From these studies, we conclude that the expression of a target
      gene in a human xenograft growing in the brain of a living mouse can be
      conditionally regulated.

PMID- 11464513
TI  - General strategy for constructing large HSV-1 plasmid vectors that co-express
      multiple genes.
AB  - Herpes simplex virus type 1 (HSV-1) plasmid vectors have a number of attractive
      features for gene transfer into neurons. In particular, the large size of the HSV
      1 genome suggests that HSV-1 vectors might be designed to co-express multiple
      genes. Here, we report a general strategy for constructing large HSV-1 plasmid
      vectors that co-express multiple genes. Each transcription unit is linked to an
      antibiotic resistance gene, and genetic selections are used to assemble large
      vectors. Using this strategy, we constructed large (26 or 31 kb) HSV-1 vectors
      that contain two transcription units and two or three genes. These vectors were
      efficiently packaged into HSV-1 particles using a helper virus-free packaging
      system. The resulting vector stocks supported the expression of two or three
      genes in both cultured cells and the rat brain. Potential applications of HSV-1
      vectors that co-express multiple genes are discussed.

PMID- 11464514
TI  - Determination of the TLR4 genotype using allele-specific PCR.

PMID- 11464515
TI  - M13-tailed primers improve the readability and usability of microsatellite
      analyses performed with two different allele-sizing methods.

PMID- 11464516
TI  - Human duplex sex determination PCR.

PMID- 11464517
TI  - Optimized growth conditions for direct amplification of cDNA clone inserts from
      culture.

PMID- 11464518
TI  - Constructing cDNA libraries with fewer clones that contain long poly(dA) tails.

PMID- 11464519
TI  - Transduction of biopsy samples: bridging gene therapy between animals and humans.

PMID- 11464520
TI  - Portable plant-tissue macerator.

PMID- 11464521
TI  - Sequence verification as quality-control step for production of cDNA microarrays.
AB  - To generate cDNA arrays in our core laboratory, we amplified about 2300 PCR
      products from a human, sequence-verified cDNA clone library. As a quality-control
      step, we sequenced the PCR products immediately before printing. The sequence
      information was used to search the GenBank database to confirm the identities.
      Although these clones were previously sequence verified by the company, we found
      that only 79% of the clones matched the original database after handling. Our
      experience strongly indicates the necessity to sequence verify the clones at the
      final stage before printing on microarray slides and to modify the gene list
      accordingly.

PMID- 11464522
TI  - Three-color imaging using fluorescent proteins in living zebrafish embryos.
AB  - The zebrafish embryo is especially valuable for cell biological studies because
      of its optical clarity. In this system, use of an in vivo fluorescent reporter
      has been limited to green fluorescent protein (GFP). We have examined other
      fluorescent proteins alone or in conjunction with GFP to investigate their
      efficacy as markers for multi-labeling purposes in live zebrafish. By injecting
      plasmid DNA containing fluorescent protein expression cassettes, we generated
      single-, double-, or triple-labeled embryos using GFP, blue fluorescent protein
      (BFP, a color-shifted GFP), and red fluorescent protein (DsRed, a wild-type
      protein structurally related to GFP). Fluorescent imaging demonstrates that GFP
      and DsRed are highly stable proteins, exhibiting no detectable photoinstability,
      and a high signal-to-noise ratio. BFP demonstrated detectable photoinstability
      and a lower signal-to-noise ratio than either GFP or DsRed. Using appropriate
      filter sets, these fluorescent proteins can be independently detected even when
      simultaneously expressed in the same cells. Multiple labels in individual
      zebrafish cells open the door to a number of biological avenues of investigation,
      including multiple, independent tags of transgenic fish lines, lineage studies of
      wild-type proteins expressed using polycistronic messages, and the detection of
      protein-protein interactions at the subcellular level using fluorescent protein
      fusions.

PMID- 11464523
TI  - Fluorescence in situ hybridization method for co-localization of mRNA and GEP.
AB  - Co-localization studies using green fluorescent protein (GFP) and fluorescence
      immunohistochemistry have become commonplace. However, co-localization studies
      using GFP and mRNA in situ hybridization are rare, in large part because typical
      in situ hybridization reaction conditions often lead to the loss of GFP
      fluorescence. Here, we describe a new fluorescence mRNA in situ hybridization
      protocol using cRNA riboprobes that leaves GFP fluorescence intact. This protocol
      is based on a urea-based hybridization buffer and the Tyramide Signal
      Amplification system. This protocol should provide researchers engaged in the use
      of GFP with a solid starting point for adapting their own in situ hybridization
      protocols.

PMID- 11464524
TI  - Increased yield of PCR products by addition of T4 gene 32 protein to the SMART
      PCR cDNA synthesis system.
AB  - Under certain conditions, T4 gene 32 protein is known to increase the efficiency
      of different enzymes, such as Taq DNA polymerase, reverse transcriptase, and
      telomerase. In this study, we compared the efficiency of the SMART PCR cDNA
      synthesis kit with and without the T4 gene 32 protein. The use of this cDNA
      synthesis procedure, in combination with T4 gene 32 protein, increases the yield
      of RT-PCR products from approximately 90% to 150%. This effect is even observed
      for long mRNA templates and low concentrations of total RNA (25 ng). Therefore,
      we suggest the addition of T4 gene 32 protein in the RT-PCR mixture to increase
      the efficiency of cDNA synthesis, particularly in cases when low amounts of
      tissue are used.

PMID- 11464525
TI  - Integration of PCR fragments at any specific site within cloning vectors without
      the use of restriction enzymes and DNA ligase.
AB  - Here, we describe a method that offers a unique way to engineer plasmids with
      precision but without digestion using restriction enzymes for the insertion of
      DNA. The method allows the insertion of PCR fragments in between any two
      nucleotides within a target plasmid. The only requirement is that the amplified
      fragments must be embedded between DNA sequences homologous to the site in which
      the integration is planned. This method is an adaptation of the QuikChange Site
      Directed Mutagenesis protocol. It is simpler than the existing cloning strategies
      and is suitable for multiparallel constructions of new plasmids. We have
      demonstrated its utility by constructing plasmids in which we have successfully
      integrated PCR fragments up to 1117 bp.

PMID- 11464526
TI  - Development of ligase-assisted spacer addition for the measurement of
      microsatellites.
AB  - Conventional methods for detecting differences in microsatellite repeat lengths
      rely on electrophoretic fractionation on long denaturing polyacrylamide gels, a
      time-consuming and labor-intensive method. Therefore, there is a need for the
      development of new and rapid approaches to routinely detect such length
      polymorphisms. The advent of techniques allowing the coupling of DNA molecules to
      solid surfaces has provided new prospects in the area of mutation detection. We
      describe here the development and optimization of the ligase-assisted spacer
      addition (LASA) method, a novel and rapid procedure based on an ELISA format to
      measure microsatellite repeat lengths. The LASA assay was successfully applied to
      a set of 11 bird samples to assess its capabilities as a genotyping method.

PMID- 11464527
TI  - [The Chilean medical scientific societies join to form a common entity].
AB  - A recent law project pretended to improve the number and distribution of clinical
      specialists throughout the country. Several Medical Scientific Societies felt
      that the diagnosis and the treatment proposed for the problem were erroneous. In
      Chile, there is no such lack of specialists but, unfortunately, they are badly
      distributed and any solution should include their better geographical
      distribution. This was the beginning of a common action by 30 Medical Scientific
      Societies, which realized that they have several problems in common, deciding to
      create an entity to face them: the Chilean Association of Medical Scientific
      Societies (ASOCIMED). This association was formed last August. In a few months of
      work it has studied its bylaws to be submitted for approval to the Member
      Societies. Also it has started to study, together with the Ministry of Public
      Health, the needs, number and distribution of specialists in the country and
      important information should be gathered from this study. ASOCIMED is already
      representing Medical Scientific Societies in the National Corporation for Medical
      Certification (CONACEM), together with the National Academy of Medicine is
      creating a National Award of Medicine and with the Health Insurance Companies is
      studying a way to face high cost diseases. During its short existence, ASOCIMED
      has faced a diversity of different issues and it seems reasonable to believe that
      it will play an important role in Chilean Medicine.

PMID- 11464528
TI  - [Changes in the patterns of drug prescription for acute myocardial infarct.
      Comparison of 2 periods].
AB  - BACKGROUND: Pharmacotherapy of Chilean patients with acute myocardial infarction
      has been recorded in 37 hospitals since 1993. AIM: To compare pharmacotherapy for
      acute myocardial infarction in the period 1993 to 1995 with the period 1997-1998.
      PATIENTS AND METHODS: Drug prescription during hospital stay was recorded in 2957
      patients admitted to Chilean hospitals with an acute myocardial infarction in the
      period 1993-1995 and compared with that of 1981 subjects admitted in the period
      1997-1998. RESULTS: When compared with the former period, in the lapse 1997-1998
      there was an increase in the frequency of prescription of aspirin (93 and 96.1%
      respectively) beta blockers (37 and 55.2% respectively) and angiotensin
      converting enzyme inhibitors (32 and 53%). The prescription of thrombolytic
      therapy did not change (33 and 33.7% respectively). There was a reduction in the
      prescription of calcium antagonists and antiarrhythmic drugs. CONCLUSIONS: During
      the period 1997-1998, the prescription of drugs with a potential to reduce the
      mortality of acute myocardial infarction, increased. The diffusion of guidelines
      for the management of this disease may have influenced this change.

PMID- 11464529
TI  - [Effects of proteolytic enzymes and sexual abstinence on alpha glucosidase
      biochemical quantification in human seminal plasma].
AB  - BACKGROUND: alpha-glucosidase is found in human seminal plasma as an acid form,
      located in accessory glands, and as a neutral form secreted almost exclusively by
      the epididymis. Quantification of alpha-glucosidase activity is a marker of the
      secretory function of the epididymis and indemnity of the sperm transport
      pathway. AIM: To obtain reference values for alpha-glucosidase in normal samples
      of seminal plasma, to evaluate its behavior in serial samples and to determine
      the effect of proteolytic enzymes. MATERIAL AND METHODS: Fifty donors, with
      normal semen analysis according to the criteria of the World Health Organization,
      were evaluated. For the study with alpha-quimotrypsin, 0.1 to 10 mg/ml of the
      enzyme was added to the seminal plasma from a group of donors. alpha-glucosidase
      was also measured in semen obtained from nine patients at different time
      intervals. RESULTS: Normal alpha-glucosidase values ranged from 14.52 to 25.69
      microU/ml. Concentrations up to 10 mg/ml of alpha-quimotrypsin (10 times of that
      usually used in the liquefaction of the semen) did not alter the quantification
      of alpha-glucosidase. Serial determinations revealed oscillations in their
      magnitude, which stayed in each patient's characteristic range. However a
      subgroup presented a marked reduction of the activity of alpha-glucosidase as the
      abstinence diminished (40%). CONCLUSIONS: Evaluation of alpha-glucosidase in
      seminal plasma gives reliable information of the secretor state of the epididymis
      and especially replaces invasive methods used to evaluate the indemnity of the
      spermatic transport from the epididymis to the anterior urethra.

PMID- 11464530
TI  - [Prevalence of calorie protein malnutrition among patients in chronic
      hemodialysis].
AB  - BACKGROUND: Malnutrition has been strongly associated with morbidity and
      mortality in hemodialysis patients. In the other hand, dialysis allows a
      nutritional improvement in patients with more than 12 months in dialysis. AIM: To
      study the prevalence of malnutrition among patients in hemodialysis. PATIENTS AND
      METHODS: We measured clinical, anthropometric and biochemical parameters of
      nutritional status in chronic hemodialysed patients. Results were related to
      individual time in dialysis. Patients with more and less than 12 months in
      dialysis were compared. RESULTS: Twenty nine patients (18 male) aged 14 to 65
      years old, were studied. Mean caloric intake was 23.8 Cal/Kg and protein intake
      was 0.7 g/Kg. Mean body mass index was 21.7 +/- 3.7 kg/m2 Thirty eight percent of
      patients had a body mass index of less than 20 kg/m2. Mean serum albumin was 4.1
      +/- 0.7 g/L; mean prealbumin was 33.5 +/- 7.9 mg% and creatinine was 9.6 +/- 2.8
      mg%. Serum cholesterol was 182 mg% and triacylglycerol 129 mg%. PCR was 42.2 +/-
      18.8 and Kt/V was 1.45 +/- 0.3. We did not find a correlation between nutritional
      markers and time in dialysis or a difference in nutritional parameters between
      patients with less or more than 12 months in dialysis. CONCLUSIONS: These
      patients in chronic dialysis have a high prevalence of caloric malnutrition,
      which may be due to a poor caloric intake. Protein malnutrition parameters were
      normal in most patients. The absence of abnormal lipid levels, common in chronic
      renal failure, is noticeable.

PMID- 11464531
TI  - [Hyperuricemia as a marker for anaerobic threshold in chronic cardiac failure].
AB  - BACKGROUND: Patients with chronic cardiac failure often have elevated plasma uric
      acid levels, that are associated to a dismal prognosis. AIM: To investigate
      possible metabolic mechanisms to explain elevated uric acid levels in these
      patients. PATIENTS AND METHODS: Eighteen patients with chronic cardiac failure
      aged 61 +/- 10 years old, without gout or renal failure and not using high doses
      of diuretics (equal or less than 80 mg/day furosemide or 50 mg/day
      hydrochlorothiazide) were studied. Plasma uric acid levels were correlated with
      anaerobic threshold, maximal oxygen uptake, plasma noradrenaline and creatinine
      and left ventricular ejection fraction, measured radioisotopically. RESULTS: Mean
      maximal oxygen uptake was 16.6 +/- 4.2 ml/kg/min. There was a negative
      correlation between uric acid levels and maximal oxygen uptake or maximal oxygen
      uptake/body surface area (r = 0.521 and -0.533 respectively, p < 0.05). Patients
      with uric acid levels over 7 mg/dl had a lower anaerobic threshold than patients
      with lower levels (9.81 +/- 2.41 and 13.08 +/- 3.28 ml/kg/min respectively, p <
      0.05). No significant differences in maximal oxygen uptake were observed in these
      two groups of patients (15.5 +/- 4.24 and 18.08 +/- 3.86 ml/kg/min respectively).
      Uric acid levels did not correlate with plasma noradrenaline, creatinine or left
      ventricular ejection fraction. CONCLUSIONS: These results suggest that a defect
      in cellular oxygenation contributes to the elevation of plasma uric acid levels
      in patients with chronic cardiac failure.

PMID- 11464532
TI  - [Ambiguous sex: prevalence at birth in the maternity ward of the clinical
      hospital of the university of Chile].
AB  - BACKGROUND: Ambiguous sex has a great phenotypic variability and is a serious
      medical and social problem. AIM: To study the prevalence of ambiguous sex among
      newborns. MATERIAL AND METHODS: As part of the ECLAMC (Cooperative Latin American
      Study of Congenital Malformations) all newborns with malformations are registered
      and the next normal newborn is considered as a control. RESULTS: 50.253 births
      occurred (between 1982 and 1999) in the University of Chile Maternity Hospital.
      The rate of congenital malformations was 6.78% and the prevalence of ambiguous
      sex was 4.7 per 10.000 births. Affected children had a lower birth weight, lower
      gestational age and a lower maternal age than controls. The most frequent
      associated malformations were of the urinary (64%) and cardiovascular systems
      (60.7%). Thirty two percent of affected children had specific syndromes.
      CONCLUSIONS: The prevalence of ambiguous sex in this study was 4.7 per 10.000
      births, which is higher than that reported in the ECLAMC (1.9 per 10,000).

PMID- 11464533
TI  - [Clinical heterogeneity of the chromosome 22q11 microdeletion syndrome].
AB  - BACKGROUND: DiGeorge anomaly, velocardiofacial syndrome and conotruncal anomaly
      face syndrome are part of a group of congenital malformations of the chromosome
      22q11 microdeletion syndrome, since they share certain phenotypic features as
      well as a common genetic abnormality. The malformations include mild facial
      dysmorphic features, conotruncal heart defects, thymic and parathyroid hypoplasia
      or aplasia and cleft palate. AIM: To describe the initial clinical presentation
      of children with clinical and molecular diagnosis of 22q11 microdeletion.
      PATIENTS AND METHODS: Ten children (seven male) with the phenotypic features of
      22q11 microdeletion syndrome are reported. Microdeletion was detected in
      peripheral lymphocytes by fluorescent in situ hybridisation (FISH) with the TUPLE
      1 DNA probe. RESULTS: Two children had abnormal karyotypes, one of them had a
      visible deletion and another child had an unbalanced translocation inherited from
      his mother who had a balanced translocation between chromosomes 14 and 22. Two of
      the 10 patients had an anterior laryngeal web, a malformation infrequently
      described in this syndrome. Five patients had the diagnosis of DiGeorge anomaly,
      had a more serious clinical presentation and a higher early mortality.
      CONCLUSIONS: The high frequency of the 22q11 microdeletion syndrome, estimated at
      1:5.000 newborns, and its variable presentations requires a high level of
      awareness for its early diagnosis and appropriate management of associated
      complications.

PMID- 11464534
TI  - [Acute hepatitis caused by virus A, E and non A-E in Chilean adults].
AB  - BACKGROUND: Sanitary and socioeconomic changes and the identification of new
      causative virus, have changed the epidemiology of hepatitis in Chile. AIM: To
      study the natural history of acute hepatitis caused by virus A, E and non A-E in
      Chilean adults. PATIENTS AND METHODS: A special study protocol was followed for
      patients with a clinical picture of acute hepatitis. Anti HAV IgM, anti HBc IgM,
      anti HEV IgG and IgM and Anti HCV antibodies were determined by ELISA. RESULTS:
      Fifty nine patients (30 male), aged 15 to 58 years old were studied. Eighty nine
      percent had jaundice and 50 to 70% had malaise and abdominal pain. Virus A was
      positive in 80%, virus E in 7%. In 14% of patients, all viral markers were
      negative. The evolution was typical in 78%, biphasic in 14% and cholestatic in
      5%. One patient had a prolonged and one a fulminant course. Mean ALT was 1148 U/l
      and mean total bilirubin was 5.5 mg/dl. Seventy three percent of cases occurred
      during early winter and spring and 27% during summer and early autumn.
      CONCLUSIONS: The main etiology of acute viral hepatitis in Chile is virus A and
      most cases occur during the rainy season. Clinical features of hepatitis non A-E
      are similar to enteral transmission forms.

PMID- 11464535
TI  - [ECLAMC: 30-year study of epidemiological surveillance of neural tube defects in
      Chile and Latin America].
AB  - BACKGROUND: There is an urgent need to assess the impact, on the incidence of
      neural tube defects, of the recently implanted flour fortification with folic
      acid in Chile. The Collaborative Study of Congenital Malformations in Latin
      America (ECLAMC) has carried out an uninterrupted register of congenital
      malformations in the last thirty years. AIM: To assess the epidemiology of neural
      tube defects in Chile and determine the most adequate base period to evaluate the
      effects of Folic acid fortification. MATERIAL AND METHODS: Analysis of ECLAMC
      database that has registered all births over 500 g from 1967. RESULTS: From 1967
      to 1999, there were 434.624 births in 18 hospitals in Chile and 3.586.569 births
      in 155 hospitals in the rest of Latin America. The rate of neural tube defects in
      Chile was 17.03 per 10.000, significantly higher than the rest of ECLAMC (14.88
      per 10.000). The prevalence of neural tube defects has a statistically
      significant secular tendency to increase in the study period and is higher among
      stillbirths, newborns with a birth weight of less than 1500 g, women and
      offspring of mothers aged less than 19 years old. CONCLUSIONS: The period 1982
      1999 is considered the best period for reference comparisons of the effects folic
      acid supplementation.

PMID- 11464536
TI  - [Motivation to quit smoking among ex-smoker university workers and students].
AB  - BACKGROUND: In Chile, 10% of deaths in adults are directly attributed to smoking.
      AIM: To identify intrinsic and extrinsic motivations to quit smoking among a
      group of subjects that quitted without external help. MATERIAL AND METHODS: The
      motivations to quit smoking were measured using the 20 items Reasons for Quitting
      Scale (RFQ), in 145 ex smokers (80 students and 65 workers at The University of
      Conception). The scale identifies intrinsic motivations in the categories health
      and self control and extrinsic motivations in the categories immediate
      reinforcement and social pressure. RESULTS: Factorial analysis with orthogonal
      rotation of the 20 items of the scale, suggested an optimal solution with five
      factors, that had a maximal impact of 0.43 and explained the motivations in up to
      a 66% of workers and 65% of students. The factors with the greater impact were
      the items of immediate reinforcement, social pressure and self control. The
      category health had only a 6% influence in the modification of smoking habits.
      CONCLUSIONS: The most important motivations to quit smoking in this sample were
      an immediate reinforcement, social pressure and self control. The analysis of
      motivations will help to orient smoking cessation programs.

PMID- 11464537
TI  - [Endoscopic coagulation with argon plasma, a therapeutic option in gastric antral
      vascular ectasia].
AB  - BACKGROUND: Gastric Antral Vascular Ectasia or Watermelon stomach is a rare cause
      of chronic gastrointestinal bleeding, often presenting as a chronic iron
      deficiency anemia. This condition can be associated with some other diseases such
      as cirrhosis, autoimmune diseases and others. We report two patients treated with
      Argon Plasma Coagulation, a 68 years old male with an ethanol related cirrhosis
      and a 72 years old female with an idiopathic Gastric Antral Vascular Ectasia. The
      characteristic endoscopic features were mistaken for many years as gastritis.
      Both patients presented with severe anemia requiring multiple transfusions as
      treatment. Due to the poor operative risk, both patients were treated with Argon
      Plasma Coagulation with good results.

PMID- 11464538
TI  - [Suprahepatic vein catheterization in 4 cases of severe septic shock].
AB  - Splanchnic hypoperfusion, with pathogenic implications for multiple organ
      failure, can occur during septic shock. We report four patients with septic shock
      in whom regional hepatosplenic splanchnic perfusion was monitored through
      suprahepatic vein catheterization and gastric tonometry. Suprahepatic lactate and
      oxygen saturation showed splanchnic hypoperfusion in all patients. These
      parameters improved only in the patient that survived. Gastric tonometry was more
      inconsistent. We conclude that suprahepatic vein catheterization could have a
      role in the management of septic shock.

PMID- 11464539
TI  - [Treatment of bipolar disorder during pregnancy and puerperium period. A case
      report].
AB  - We report a 37 years old woman with a severe bipolar disorder, that became
      pregnant during treatment with lithium. The patient and her family were informed
      about the 0.05-0.1% risk of cardiac malformations of the newborn, but decided to
      maintain her pregnancy and not to discontinue the use of lithium, fearing a
      relapse of her psychiatric ailment. She continued under medical surveillance and
      had a normal delivery, but no breast feeding was allowed.

PMID- 11464540
TI  - [Scientific ethics and frozen embryos].
AB  - BACKGROUND: Scientific Ethics is the theory and praxis of decisions.
      Philosophical Ethics is presented as the theory and praxis of the good. As the
      good differs among cultures, Philosophical Ethics is dependent on the endo
      cultural good conception. The decision (included that one of adhesion or not to a
      world vision) depends on neuro-psychic specific factors: i) cognitive factors
      that include mostly the knowledge of the alternatives and their consequences and
      the ideological or religious conception of good in relation to the alternatives;
      ii) affective factors that make alternatives pleasant, unpleasant or neutral,
      attractive, repulsive or neutral; iii) emotional factors that associate to
      alternatives anger, peace or neutrality, sadness, happiness or neutrality; iv)
      value factors that assign importance, triviality or neutrality to alternatives,
      or assign them significance, irrelevancy or neutrality. There are unspecific
      factors such as the psychic energy, desire or others. Mixed factors such as
      attitude, motivation, intention and others. Scientific Ethics deals with the mind
      as a materio-energetic process which is different from the soul, eggs and embryos
      of any species are full individuals of that species, because, they have initiated
      a copy of their genome that specify, give autonomy and define them as
      individuals. For Scientific Ethics to leave frozen embryos like that for ever, to
      defrost and get rid of them or to use their cells for science are synonymous of
      killing them. To defrost them to use their cells as stem cells for somatic cell
      therapy or to implant them into uteri to continue their development is to
      maintain alive their cells, but only the implantation allows their maintenance as
      individuals, thus, being the only compatible with the Christian ethics. The
      compatibility of these alternatives with other ethics is discussed.

PMID- 11464541
TI  - Alzheimer disease: 100 years later.
AB  - Almost 100 years since the first clinical report of a case of Alzheimer disease
      (AD), three early-onset and two late-onset AD genes have been identified. While
      rare mutations in the early-onset genes (amyloid precursor protein, and
      presenilins 1 and 2) lead to increased generation of specific forms of the
      amyloid beta protein (A,beta), common polymorphisms in the late-onset genes
      (apolipoprotein E and alpha 2-macroglobulin) are thought to alter the clearance
      and degradation of A,beta in brain. Although definite proof for a direct link
      between altered A beta generation/clearance and neurodegeneration has not yet
      been attained, mechanism-based approaches for the therapeutic treatment of AD
      based on lowering levels of the potentially pathogenic A beta are currently
      underway. The recent discovery of the enzymes (secretases) responsible for
      generating A beta have paved the way for the development of such drugs and
      increase the prospects for successful therapeutic intervention to arrest AD
      neuropathogenesis.

PMID- 11464542
TI  - [Irritable bowel syndrome].
AB  - Irritable bowel syndrome is a functional disease with highly variable symptoms
      and difficult to diagnose. The clinical picture is fundamental to reach a correct
      diagnosis and discard other gastrointestinal diseases. It etiology is not well
      known; psychological problems and stress probably play an important role in the
      development of the disease. Irritable bowel syndrome impairs the quality of life
      of patients and is a frequent cause of consultation in primary care. Its therapy
      is basically symptomatic and requires psychological support. The physician must
      warn his/her patients that immediate results are rarely obtained and that a
      prolonged clinical follow up may be necessary.

PMID- 11464543
TI  - [General objectives for a health organization reform in Chile].

PMID- 11464544
TI  - [Medical epistemology].

PMID- 11464545
TI  - [Sleepiness attacks while driving: adverse effects of new antiparkinson drugs].

PMID- 11464546
TI  - Morbidity in newborn babies.

PMID- 11464547
TI  - A suspected case of temporal arteritis.

PMID- 11464548
TI  - Key developments in paediatrics.

PMID- 11464549
TI  - Child sex abuse--a guide for GPs.

PMID- 11464550
TI  - Promoting the health of children.

PMID- 11464551
TI  - Growing pains: a diagnosis of exclusion.

PMID- 11464552
TI  - Using spirometry in general practice.

PMID- 11464554
TI  - Unlocking the doors of perception.

PMID- 11464555
TI  - Is it a bird? Is it a plane? Ultra-rapid visual categorisation of natural and
      artifactual objects.
AB  - Visual processing is known to be very fast in ultra-rapid categorisation tasks
      where the subject has to decide whether a briefly flashed image belongs to a
      target category or not. Human subjects can respond in under 400 ms, and event
      related-potential studies have shown that the underlying processing can be done
      in less than 150 ms. Monkeys trained to perform the same task have proved even
      faster. However, most of these experiments have only been done with biologically
      relevant target categories such as animals or food. Here we performed the same
      study on human subjects, alternating between a task in which the target category
      was 'animal', and a task in which the target category was 'means of transport'.
      These natural images of clearly artificial objects contained targets as varied as
      cars, trucks, trains, boats, aircraft, and hot-air balloons. However, the
      subjects performed almost identically in both tasks, with reaction times not
      significantly longer in the 'means of transport' task. These reaction times were
      much shorter than in any previous study on natural-image processing. We conclude
      that, at least for these two superordinate categories, the speed of ultra-rapid
      visual categorisation of natural scenes does not depend on the target category,
      and that this processing could rely primarily on feed-forward, automatic
      mechanisms.

PMID- 11464556
TI  - Adaptation reveals a neural code for the visual location of orientation change.
AB  - We apply an adaptation technique to explore the neural code for the visual
      location of textures defined by modulation of orientation over space. In showing
      that adaptation to textures modulated around one orientation shifts the perceived
      location of textures modulated around a different orientation, we demonstrate the
      existence of a neural code for the location of orientation change that
      generalises across orientation content. Using competitive adaptation, we
      characterise the neural processes underlying this code as single-opponent for
      orientation, that is with concentric excitatory/inhibitory receptive areas tuned
      to a single orientation.

PMID- 11464557
TI  - Perceived depth of 3-D objects in 3-D scenes.
AB  - Effects of information specifying the position of an object in a 3-D scene were
      investigated in two experiments with twelve observers. To separate the effects of
      the change in scene position from the changes in the projection that occur with
      increased distance from the observer, the same projections were produced by
      simulating (a) a constant object at different scene positions and (b) different
      objects at the same scene position. The simulated scene consisted of a ground
      plane, a ceiling plane, and a cylinder on a pole attached to both planes. Motion
      parallax scenes were studied in one experiment; texture-gradient scenes were
      studied in the other. Observers adjusted a line to match the perceived internal
      depth of the cylinder. Judged depth for objects matched in simulated size
      decreased as simulated distance from the observer increased. Judged depth
      decreased at a faster rate for the same projections shown at a constant scene
      position. Adding object-centered depth information (object rotation) increased
      judged depth for the motion-parallax displays. These results demonstrate that the
      judged internal depth of an object is reduced by the change in projection that
      occurs with increased distance, but this effect is diminished if information for
      change in scene position accompanies the change in projection.

PMID- 11464558
TI  - The absence of depth constancy in contour stereograms.
AB  - Stereoscopic surfaces constructed from Kanizsa-type illusory contours or explicit
      luminance contours were tested for three-dimensional (3-D) shape constancy. The
      curvature of the contours and the apparent viewing distance between the surface
      and the observer were manipulated. Observers judged which of two surfaces
      appeared more curved. Experiment 1 allowed eye movements and revealed a bias in 3
      D shape judgment with changes in apparent viewing distance, such that surfaces
      presented far from the observer appeared less curved than surfaces presented
      close to the observer. The lack of depth constancy was approximately the same for
      illusory-contour surfaces and for explicit-contour surfaces. Experiment 2 showed
      that depth constancy for explicit-contour surfaces improved slightly when
      fixation was required and eye movements were restricted. These experiments
      suggest that curvature in depth is misperceived, and that illusory-contour
      surfaces are particularly sensitive to this distortion.

PMID- 11464559
TI  - Imperfect invariance to object translation in the discrimination of complex
      shapes.
AB  - The positional specificity of short-term visual memory for a variety of 3-D
      shapes was investigated in a series of 'same'/'different' discrimination
      experiments, with computer-rendered stimuli displayed either at the same or at
      different locations in the visual field. For animal-like shapes, we found
      complete translation invariance, regardless of the interstimulus similarity, and
      irrespective of direction and size of the displacement (experiments 1 and 2).
      Invariance to translation was obtained also with animal-like stimuli that had
      been 'scrambled' by randomizing the relative locations of their parts (experiment
      3). The invariance broke down when the stimuli were made to differ in their
      composition, but not in the shapes of the corresponding parts (experiments 4 and
      5). We interpret this pattern of findings in the context of several current
      theories of recognition, focusing in particular on the issue of the
      representation of object structure.

PMID- 11464560
TI  - Stereomotion speed perception is contrast dependent.
AB  - The effect of contrast on the perception of stimulus speed for stereomotion and
      monocular lateral motion was investigated for successive matches in random-dot
      stimuli. The familiar 'Thompson effect'--that a reduction in contrast leads to a
      reduction in perceived speed--was found in similar proportions for both binocular
      images moving in depth, and for monocular images translating laterally. This
      result is consistent with the idea that the monocular motion system has a
      significant input to the stereomotion system, and dominates the speed percept for
      approaching motion.

PMID- 11464561
TI  - Cognitive suppression of tilt sensations during linear horizontal self-motion in
      the dark.
AB  - On the basis of models of otolith functioning, one would expect that, during
      sinusoidal linear self-motion in darkness, percepts of body tilt are experienced.
      However, this is normally not the case, which suggests that the otoliths are not
      responsive to small deviations from the vertical of the gravito-inertial force
      vector acting on them. Here we show that this is incorrect. Subjects usually know
      on what kind of linear motion device they are (going to be) moved, having seen it
      prior to experimentation. This may result in a cognitive suppression of such
      otolith responses. In the present study, subjects were kept completely unaware of
      how they were moved and were asked to report on how they thought they moved.
      About 50% of the reports included tilt percepts almost immediately. It is
      concluded that this reveals the presence of otolith responsiveness to even small
      and short-lived deviations of the gravito-inertial force vector from verticality,
      a responsiveness which is suppressed when (prior) cognitions exist that the
      motion path is purely in the horizontal plane.

PMID- 11464562
TI  - Multistability of overlapped face stimuli is dependent upon orientation.
AB  - Stimuli composed of two overlapped faces, one rotated 45 degrees clockwise and
      the other 45 degrees counterclockwise, produce perceptual rivalry whereby both
      faces cannot be simultaneously perceived. We obtained subjective and quantitative
      measures of this rivalry effect and examined if it persists with inverted
      stimuli. Our results show that upright stimuli are multistable, with alternations
      occurring from one face to the other within 2 s. Inverted stimuli were instead
      perceived as ambiguous in half of the trials, indicating weaker perceptual
      rivalry in that condition. We suggest that overlapped faces produce perceptual
      rivalry because each face is readily interpreted into a Gestalt, an effect that
      in turn is dependent upon orientation.

PMID- 11464563
TI  - Familiarisation with faces selectively enhances sensitivity to changes made to
      the eyes.
AB  - Two experiments were designed to isolate the facial information utilised in the
      learning of new faces. In experiments 1 and 2, two groups of subjects were each
      trained on different groups of faces by means of a dynamic video presentation.
      They were then shown both trained and novel faces in a same-different decision
      task, where 'different' trials included manipulations of internal and external
      facial features, and the task was to decide whether two images were identical or
      had a difference in one or more features. Both experiments showed that hair
      change was most easily detected in untrained (unfamiliar) faces. When faces had
      been trained (familiar), detection of eye changes was selectively enhanced and
      sensitivity to hair changes was maintained. While previous studies have suggested
      that familiar face representations are weighted towards their internal features,
      our experimental results show that this is due to selective enhancement of
      sensitivity to changes made to the eyes alone, with no reduction in the salience
      of the hair. Moreover, within the limits of the familiarisation used here, there
      was no enhancement of the representation of the other internal face features
      examined.

PMID- 11464564
TI  - People don't keep their heads still when looking to one side, and other people
      can tell.
AB  - Twenty pairs of photographs were made of adults looking 25 degrees to the left
      and 25 degrees to the right while attempting to face forwards. The eye regions of
      each photograph were concealed. Twenty adults attempted to sort each pair into
      left-looking and right-looking pictures. They were successful 65% of the time, p
      < 0.001. This suggests models have difficulty looking to one side without a
      perceptible head turn or comparable facial cue. This previously unrecognised
      phenomenon has implications for research on detection of gaze.

PMID- 11464565
TI  - The lady's not for turning: rotation of the Thatcher illusion.
AB  - Inversion is especially detrimental to the processing of faces. This is clearly
      demonstrated by the Thatcher illusion. It has been suggested that this detriment
      is due to a loss of holistic or configural processing for inverted faces
      (Bartlett and Searcy, 1993 Cognitive Psychology 25 281-316). Sturzel and
      Spillmann (2000 Perception 29 937-942) suggest that this loss of configural
      processing occurs suddenly as a face is rotated slowly from upright to inverted.
      This hypothesis is tested in a study of the reaction times taken to indicate that
      a face has been Thatcherised at various angles of orientation. The results
      suggest that there is a gradual loss of configural information rather than a
      rapid switch from one type of processing to another.

PMID- 11464566
TI  - Hospitals can control patient days to stem nurse demand.

PMID- 11464567
TI  - How cancer centers of excellence lose money on 2nd opinion patients.

PMID- 11464568
TI  - Cardiovascular services are great opportunities and risks for hospitals.

PMID- 11464569
TI  - Boards have important strategic decisions to make in 2001.

PMID- 11464570
TI  - Clinical care coordinators help hospitalists cut ALOS by up to 50%.

PMID- 11464571
TI  - Last 25 years proves that little will change.

PMID- 11464572
TI  - Rural residents use urban hospitals, which are more expensive.

PMID- 11464573
TI  - Cancer rates and deaths from cancers continued to decline between 1992 and 1998.

PMID- 11464574
TI  - Are singleton assisted reproductive technology pregnancies at risk of
      prematurity?
AB  - PURPOSE: Our purpose was to determine the risk of premature delivery among
      singleton pregnancies derived from assisted reproduction technology (ART).
      METHODS: Ninety-five singleton ART pregnancies and 190 matched spontaneous
      pregnancies were assessed for preterm delivery rates, pregnancy complications,
      and cesarean section rates in a retrospective study at an academic medical
      center. RESULTS: Among the ART singleton deliveries group (n = 95), 19 (20%) were
      preterm, which was statistically significantly higher than the 4% (8 of 190)
      found in the control group. Among the pregnancies achieved by intracytoplasmic
      sperm injection (ICSI) in the severe male-factor infertility subgroup (n = 22),
      only one preterm delivery occurred (4.5%). CONCLUSIONS: Singleton ART pregnancies
      are at an increased risk of preterm delivery compared to singleton pregnancies
      after spontaneous conception. The higher rate may be attributed to various
      infertility cofactors, such as uterine malformations, previous operative
      procedures that involved cervical dilatation, and a history of pelvic infection.
      This is supported by the finding that ICSI-derived pregnancies in couples with
      strict male-factor infertility are not at an increased risk of preterm delivery.

PMID- 11464575
TI  - The effect of exogenous luteinizing hormone (LH) on oocyte viability: evidence
      from a comparative study using recombinant human follicle-stimulating hormone
      (FSH) alone or in combination with recombinant LH for ovarian stimulation in
      pituitary-suppressed women undergoing assisted reproduction.
AB  - PURPOSE: The purpose of this prospective, randomized study was to compare ovarian
      response and oocyte and embryo yields in women undergoing ovulation induction for
      IVF/ICSI using recombinant human FSH (rhFSH) alone or in combination with
      recombinant human LH (rhLH). METHODS: Patients were randomized to receive rhFSH
      alone (group F; n = 13) or rhFSH + rhLH (group L; n = 15). rhFSH was administered
      according to a step-down protocol; patients assigned to group L received rhLH at
      a fixed dose of 75 IU (1 ampoule) throughout the treatment period. RESULTS: The
      total dose of rhFSH, number of growing follicles, and serum concentrations of
      estradiol (E2) on the day of hCG administration were similar in both treatment
      groups. However, the percentage of metaphase II oocytes and fertilization rate
      were significantly higher in group F than in group L. The lower fertilization
      rates associated with rhLH were also seen in a subgroup of patients from group L
      who had undergone a previous ART cycle stimulated with FSH only and thus acted as
      their own controls. However, when in vitro fertilization (IVF) and
      intracytoplasmic sperm injection cycles were considered separately, differences
      in fertilization rates were statistically significant only for oocytes treated by
      conventional IVF. CONCLUSIONS: This study shows that the addition of recombinant
      LH to recombinant FSH in pituitary-suppressed women undergoing ART does not
      improve the ovarian response and even may have a negative impact on oocyte
      maturation and fertilization.

PMID- 11464576
TI  - Comparison of the cryopreservation of human embryos obtained after
      intracytoplasmic sperm injection with a slow cooling or an ultrarapid cooling
      procedure.
AB  - PURPOSE: Our purpose was to compare an ultrarapid method (URM) modified with
      dimethyl sulfoxide (Me2SO) to a slow method (SM) with propanediol (PROH) for the
      cryopreservation of extra human embryos in a program of intracytoplasmic sperm
      injection (ICSI). METHODS: The extra embryos of 160 patients were cryopreserved
      in a prospective and randomized manner (drawing lots) by a modified URM (3 M
      Me2SO/0.25 M sucrose/thawing in three sucrose gradients) (Group I) or by a SM
      (1.5 M Propanediol/program 0-Cryologic CL863) (Group II). A total of 103 cycles
      has been thawed thus far. The number of thawed cycles was 58 for group I and 45
      for group II. RESULTS: The mean age (group I, 31.3 +/- 4.5; group II, 31.9 +/-
      4.3) did not differ between the groups (P = 0.38). The number of frozen embryos
      (group I, 6.6 +/- 3.2; group II, 6.5 +/- 3.2) was similar (P = 0.49) for the two
      groups, as was the number of thawed embryos (P = 0.52) (group I, 6.5 +/- 2.9;
      group II, 6.2 +/- 3). The survival rate was higher (P < 0.01) for group II (83.3
      +/- 23%) than for group I (69.2 +/- 28.7%). The cleavage rate was also higher (P
      < 0.01) for group II (56.8 +/- 31%) compared with group I (24.2 +/- 22.4%). The
      number of embryos transferred did not differ (P = 0.14) between the groups (group
      I, 3.16 +/- 1.2; group II, 3.5 +/- 1.0). The implantation rate (group I, 6.3%;
      group II, 13.8%) was significantly different between groups (P = 0.034).
      Pregnancy rates per thawed and transferred cycle were higher for group II (33.3
      and 36.6%, respectively) compared with group I (13.8 and 16%, respectively), and
      these differences were significant (P = 0.03 and P = 0.03, respectively).
      CONCLUSION: The data obtained suggest that the SM is superior to the URM for the
      cryopreservation of extra embryos after ICSI.

PMID- 11464577
TI  - Alternative embryo transfer on day 3 or day 5 for reducing the risk of multiple
      gestations.
AB  - PURPOSE: This study was carried out to reduce the possibility of high-order
      multiple gestations and the failure of embryo transfer by determining their
      replacement date based on the number and quality of 2-day embryos. METHODS: All
      zygotes were cocultured with cumulus cells in 10 microliters of YS medium
      containing 10% human follicular fluid (hFF) for 48 or 96 hr. In period I, all
      embryos were transferred on day 3 (1032 cycles). In period II, the embryos were
      transferred on either day 3 or day 5 by determining their replacement date based
      on the number and quality of 2-day embryos: there were 2701 patients in whom
      embryos were replaced on day 3 (in the case that the number of zygotes was less
      than eight and the number of good-quality embryos was less than three) and 1952
      patients less than 40 years old in whom embryos were replaced on day 5 (in the
      case that the number of zygotes was eight or more and/or the number of good
      quality embryos was three or more). On the other hand, patients who were 40 years
      old or more were alloted to day 3 transfer cycles, regardless of the number and
      quality of the 2-day embryos, due to the possibility of their not producing
      blastocyst-stage embryos in vitro. RESULTS: The number of embryos transferred in
      period II was 2.9 +/- 0.6, while that in period I was 3.7 +/- 0.5. The multiple
      pregnancy rate was significantly decreased in period II (30.7%) compared to that
      (49.6%) in period I, while the pregnancy and implantation rates in period II
      (36.1 and 16.4%, respectively) were not lower than those (34.9 and 16.1%,
      respectively) in period I. The rate of triplet or more gestations was
      significantly minimized in period II (2.3%) compared to that in period I (26.5%).
      CONCLUSIONS: We propose that determination of the date on which embryos should be
      transferred based on the number and quality of embryos on day 2 may help to
      maintain an acceptable pregnancy rate, while minimizing embryo transfer failure
      and high-order multiple gestations.

PMID- 11464578
TI  - Gonadotropin-releasing hormone messenger ribonucleic acid and protein expression
      in Vero cells.
AB  - PURPOSE: Interleukin-1 (IL-1) is a major regulator of local cellular interactions
      during embryonic implantation. We hypothesized that gonadotropin-releasing
      hormone (GnRH) may also play a role in the embryonic/epithelial dialogue during
      early implantation. To examine this hypothesis, we examined the ability of IL-1
      to regulate GnRH mRNA and protein expression in Vero cells. METHODS: Viable Vero
      cells (1 x 10(5)/well) were cultured in multiple-well tissue culture plates for
      in vitro studies and in 4-well chamber slides for immunohistochemical study.
      Confluent Vero cells were cultured with increasing concentrations of recombinant
      human IL-1 beta for an additional 24 hr. Vero cell expression of GnRH and GnRH
      receptor mRNAs was measured with polymerase chain reaction (PCR) and nested PCR,
      respectively. GnRH protein expression was validated by immunohistochemistry
      study. The quantitative level of GnRH mRNA expression regulated by IL-1 beta in
      Vero cells was determined by quantitative competitive PCR (QC PCR) with standard
      curve methodology. RESULTS: RT-PCR revealed beta-actin, GnRH, and GnRH receptor
      mRNA expression in Vero cell cultures. Immunostaining confirmed the presence of
      GnRH protein in Vero cells. Quantitative PCR demonstrated IL-1 beta up-regulation
      of Vero cell GnRH mRNA expression (p < 0.05). CONCLUSIONS: These results suggest
      that Vero cell mRNA and protein expression of GnRH may play a substantial role in
      early embryo/epithelial dialogue during embryo coculture, with an embryotrophic
      effect due to expression of GnRH by Vero cells.

PMID- 11464579
TI  - IL-18, a product of choriodecidual cells, increases during premature rupture of
      membranes but fails to turn on the Fas-FasL-mediated apoptosis pathway.
AB  - PROBLEM: IL-18 is a novel cytokine, which promotes inflammation and apoptosis.
      This study examines its expression pattern, site of production, and levels in the
      amniotic fluid (AF) during pregnancy complications such as preterm labor and
      preterm premature rupture of membranes (pPROM). The ability of IL-18 to induce
      the Fas-Fas ligand (FasL)/caspase-mediated apoptotic pathway is also studied.
      METHODS: Amniochorion collected at term was placed in an organ explant system. IL
      18 mRNA expression was studied by RT-PCR. IL-18 mRNA and peptide were localized
      by in situ hybridization and immunohistochemistry. IL-18 in the AF of women with
      pPROM, with preterm labor with no rupture of membranes, and at term was measured
      using ELISA. Multiplex PCR was used to study the expression pattern of
      proapoptotic genes such as Fas, FasL, caspase 8, and Fas-associated death domain
      (FADD). ELISA was also used to measure the release of soluble Fas from IL-18
      stimulated amniochorion in culture media. RESULTS: IL-18 is a constitutively
      expressed gene in human chorion and decidua but not in human amnion and increases
      in the AF of women with pPROM [2.9 +/- 3.3 ng/ml (SD)] compared to women with
      preterm labor (1.1 +/- 0.67 ng/ml; P < 0.05) and term (0.9 +/- 0.73 ng/ml; P <
      0.05). IL-18 induces Fas expression, whereas FADD is a constitutively expressed
      gene in human fetal membranes. IL-18 failed to induce FasL or caspase 8
      expressions. Soluble Fas release from amniochorion was increased after IL-18
      stimulation. CONCLUSION: Chorion and decidua are a source of IL-18, whose
      concentrations are increased in the AF during pPROM. IL-18 induced Fas expression
      in amniochorion; however, it failed to turn on other genes in the Fas-FasL
      apoptosis pathway including FasL and caspase 8.

PMID- 11464580
TI  - Transcervical embryoscopy in missed abortion.
AB  - PURPOSE: The present study was conducted to determine the usefulness of
      transcervical embryoscopy in diagnosing localized and systemic defects in
      embryonic morphogenesis of missed abortions. METHODS: The study population
      consisted of 24 women with the final diagnosis of missed abortion. Prior to the
      instrumental evacuation of the uterus a rigid hysteroscope was passed
      transcervically into the amniotic cavity to obtain a detailed view of the embryo.
      Karyotyping was attempted in all cases included in this study. RESULTS: An embryo
      could be visualized in 19 cases. Ten embryos showed multiple developmental
      defects. CONCLUSIONS: In cases of early failure of pregnancy, embryoscopy permits
      visualization of the embryo in utero, unaffected by the damage usually caused by
      its instrumental evacuation or spontaneous passage. This technique can be a
      helpful tool for pathologists and geneticists in enhancing their understanding of
      human embryonic malformations, but more importantly, it improves clinical care
      and follow-up, especially in cases of repeated abortions.

PMID- 11464581
TI  - Multiplex PCR for screening of microdeletions on the Y chromosome.
AB  - PURPOSE: The aim of this study was to develop a multiplex PCR protocol, which
      could be suitable for screening of microdeletions in the three azoospermia factor
      (AZF) regions on the Y chromosome. METHODS: In the screening protocol, 36 known
      sequence tagged site (STS) primer pairs were first tested in single PCR reactions
      and thereafter combined in multiplex PCR to test for specificity and sensitivity
      in order to develop a stable and reliable multiplex PCR assay to detect Y
      microdeletions. RESULTS: Of the 36 primers tested, 11 turned out not to be
      specific or produced PCR products that were too weak, and they were therefore not
      used in the multiplex PCR. The remaining 25 STSs were selected on the basis of
      their ability to be reproducibly amplified with each other using identical
      amplification conditions. Five multiplex sets, each consisting of five primer
      pairs, were established in the multiplex PCR setup. CONCLUSION: The multiplex PCR
      protocol presented in this study is an easy and reliable method for detection of
      Y chromosome microdeletions and could be used for screening of infertile men to
      allow genetic counseling about the risk of transmitting infertility from father
      to son.

PMID- 11464582
TI  - Capacity for hormone production of cultured trophoblast cells obtained from
      placentae at term and in early pregnancy.
AB  - PROBLEM: There is an increased doubt about the identity of isolated
      cytotrophoblast cells at term. Therefore, we compared pregnancy serum levels of
      three hormones [human placental lactogen (hPL), human chorionic gonadotropin
      (hCG), and leptin] with the capacity for hormone production of early placentae
      [EP; 8-13 weeks of gestation (WG)] and term placentae (TP; 38-42 WG). METHODS:
      Serum levels of these hormones were determined in 15 paired maternal (7-41 WG)
      and fetal (37-41 WG) samples. Cytotrophoblast cells were isolated from term (TP;
      38-42 weeks) and early (EP; 8-13 weeks) placentae by enzymatic digestion and
      subsequent purification on a Percoll gradient. These cells were cultured for 6
      days. The production of the hormones hPL, hCG, and leptin was determined as
      release during culture + cell content after culture - cell content before
      culture. RESULTS: Serum levels (mean +/- SD; n = 15) at 7-12 and 37-41 WG were
      89,652 +/- 21,431 and 13,620 +/- 5854 mIU/ml for hCG, 400 +/- 182 and 7088 +/-
      2030 ng/ml for hPL, and 12,675 +/- 4266 and 32,236 +/- 10,961 pg/ml for leptin,
      respectively. For cultured cells from EP and TP, hCG and hPL showed different
      patterns of release during the first 2-3 days. While the release of these two
      hormones by EP cytotrophoblast cells continued during 6 days in culture, their
      concentrations reached a plateau for TP cytotrophoblasts between 4 and 6 days.
      Leptin was undetectable (< 15 pg/ml) in TP cell cultured media, while for EP all
      three hormones showed the same release profiles. Production calculated for 30,000
      TP trophoblast cells cultured for 6 days (n = 8) was 2-31 mIU for hCG and 0.5-2
      ng for hPL. For EP (n = 11), it was 50-1070 mIU for hCG, 15-323 ng for hPL, and
      137-580 pg for leptin. Net synthesis of hCG and hPL for TP was > 10-fold and < 1
      fold, respectively. In contrast, the production of all three hormones for EP was
      at least 100 times the initial cell content. CONCLUSIONS: These results
      demonstrate that trophoblasts from early pregnancy show much higher production
      rates of hCG, hPL, and leptin than at term. However, the in vitro findings are
      difficult to be reconciled with the different serum concentrations of the two
      hormones hPL and leptin observed during the course of pregnancy.

PMID- 11464583
TI  - The biological significance of phospholipase C beta 1 gene mutation in mouse
      sperm in the acrosome reaction, fertilization, and embryo development.
AB  - PURPOSE: We carried out this study to evaluate the biological significance of
      phospholipase C beta 1 gene mutation in mouse sperm in the acrosome reaction,
      fertilization, and embryo development. METHODS: Study subjects were divided into
      two groups according to the sperm [intact phospholipase C (PLC) beta 1 and PLC
      beta 1-/- C57BL/6J x CBA F1 mouse sperm] used. The positive acrosome reaction
      rate labeled with fluorescein isothiocyanate-Pisum sativum agglutinin, the
      fertilization rate, and the rate of embryos developed to the stage of morula or
      blastocyst in the two groups were compared. RESULTS: The mouse sperm null for the
      PLC beta 1 gene showed a lower acrosome reaction rate than control sperm (69.2 vs
      50.9%, P < 0.05). And the fertilization rate and the rate of embryos developed to
      the stage of morula or blastocyst were also lower in the group using PLC beta 1-/
      mouse sperm compared to the intact group (P < 0.05; 73.5 vs 51.8% and 15.7 vs
      4.3%, respectively). CONCLUSIONS: Mutation of the PLC beta 1 gene in the mouse
      sperm reduces the acrosome reaction rate, fertilization rate, and embryo
      development rate, which may be the etiologic factors responsible for the low
      reproductive rate of PLC beta 1-/- mouse.

PMID- 11464584
TI  - An intracytoplasmic sperm injection pregnancy with a globozoospermic male.

PMID- 11464585
TI  - [Atypical regenerative changes, dysplasia, and carcinoma in situ in chronic
      gastritis associated with Helicobacter pylori].
AB  - In the present work we study the association between chronic active gastritis
      (CAG), atypical regeneration and dysplasia and gastric Helicobacter pylori (HP)
      infection. We study two groups of endoscopic biopsies. Regenerative changes and
      dysplasia were evaluated according to Gandur-Maymneh et al. classification which
      was simplified in typical and atypical regeneration, and mild and severe
      dysplasia. The group I included 94 patients with CAG, 9 with chronic non active
      gastritis (CNAG) and 2 with normal gastric mucosa. CAG was graded according to
      activity in; severe 28 patients; moderate 54 patients and; mild 12 patients. HP
      association in these cases was 100%, 77% and 25%. In cases of CNAG HP was present
      in 22%, there were not HP in normal gastric mucosa. There were atypical
      regeneration in 25% of moderate CAG and in 42% of severe CAG. Mild dysplasia was
      present in 7.5 and 25% in cases of moderate and severe CAG. Two biopsies showed
      severe dysplasia. In addition, intestinal metaplasia was found in 15% of CAG, the
      metaplasia was present in 25% of cases with CAG and atypical regeneration; in 54%
      of cases with mild dysplasia and; in 100% on cases with severe dysplasia. The
      group II included 9 cases of gastric cancer of intestinal type, 7 cases of
      diffuse type, and 4 cases of mixed type. In all these cases there was viewed CAG
      associated to HP infection in non-neoplastic mucosa. In 75% of cases there were
      showed atypical regeneration and 60% presented some type of dysplasia. There was
      transition between atypical regeneration and dysplasia in 6 cases of intestinal
      gastric cancer and in 3 cases of mixed type. We found relationship between the
      intensity of CAG and HP colonization, and the association with atypical
      regeneration and dysplasia.

PMID- 11464586
TI  - [Utility of botulinum toxin in stasis esophagitis secondary to achalasia. Report
      of a case].
AB  - Upper gastrointestinal bleeding is an infrequent complication of achalasia.
      Stasis esophagitis is a rare cause of esophageal bleeding in which conventional
      forms of treatment may be associated with a high risk of complications. Botulinum
      toxin has emerged as a therapeutic alternative with few secondary effects. We
      present a case report of achalasia complicated by upper gastrointestinal bleeding
      secondary to stasis esophagitis which was successfully treated with botulinum
      toxin. Interesting aspects related to stasis esophagitis and the potential role
      of botulinum toxin in achalasia are discussed.

PMID- 11464587
TI  - [Gastric stromal tumor with myxoid degeneration. Report of a case and review of
      the literature].
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST's) represent a heterogeneous
      group of neoplasms that have as their common histologic denominator an immature
      proliferation of epithelioid or spindle cells. Although originally believed to
      represent atypical variants of leiomyoma or leiomyosarcoma, recent studies have
      demonstrated that only a subset of such tumors actually display well developed
      immunohistochemical, ultrastructural features of smooth muscle differentiation.
      Most gastrointestinal mesenchymal tumors are of uncertain histogenesis. Current
      studies have shown a striking morphological and immunophenotypic similarities of
      these tumors with the interstitial cells of Cajal. And that they may originate
      from stem cells that differentiate toward a pacemaker cell phenotype. Most GIST's
      have a co-expression of Kit (CD117) or CD34, which is also express in
      interstitial cells of Cajal. OBJECTIVE: This review will attempt to summarize the
      current knowledge and understanding of these lesions based on review of the
      literature, with an analysis of the criteria for distinguishing between benign
      and malignant tumors. METHOD: We report a Gastrointestinal Stromal Tumor of the
      stomach with prominent cystic degeneration. The patient had diarrhea, abdominal
      pain and was found to have abdominal mass. X-ray and computed axial tomography
      examination showed a lesion that seems to be a pancreatic cystic lesion. At
      laparotomy a large intramural tumor located in the stomach was found.
      Histologically, the lesion was composed of epithelioid and spindle cells embedded
      in an abundant myxoid stroma. Tumor cells showed positive staining for vimentin
      and CD34 positive. We conclude that the diagnosis of gastrointestinal stromal
      tumor whit prominent cystic degeneration can be made in this case.

PMID- 11464588
TI  - [Multiorgan resection in T4 colonic adenocarcinoma. Report of a case].
AB  - BACKGROUND: Colorectal cancer is the second among gastrointestinal malignancies
      in Mexico Locally advanced disease or metastatic lesions are frequently found. To
      resect or not such a tumor is a difficult decision. OBJECTIVE: To report a case
      of colon cancer with multivisceral invasion resected and to review the published
      information. CLINICAL MATERIAL: A 43 year-old Mexican male with rectal bleeding
      and weight loss with a tumor located in transverse colon with direct invasion to
      stomach. CT scan demonstrated invasion to spleen and pancreas. En-bloc radical
      extended right colectomy, total gastrectomy, distal pancreatectomy, splenectomy
      and left adrenalectomy was performed. Adjuvant chemotherapy was used. At 12-month
      follow-up he is asymptomatic, without neoplasic activity and with good quality of
      life. CONCLUSION: An aggressive multiorganic resection in T4 colorectal tumors is
      justified in selected cases. The high morbidity and mortality of these procedures
      must be evaluated individually, and if permissive must be performed.

PMID- 11464589
TI  - [Acute pancreatitis secondary to typhoid fever in a preschool child].
AB  - INTRODUCTION: A case of child with acute pancreatitis associated with typhoid
      fever is reported herein. CASE REPORT: A four years old child was admitted to the
      pediatric emergency room with an acute abdomen and fever. He was submitted to a
      diagnostic laparotomy and mesenteric adenitis was the only finding. During the
      postoperative period, he persisted with abdominal pain and fever. Laboratory
      studies and abdominal ultrasonography revealed an acute pancreatitis. Also,
      Salmonella typhi was isolated from blood and stool cultures. Treatment for
      pancreatitis included nasogastric catheter and total parenteral nutrition.
      Typhoid fever was treated with ampicillin. Thereafter, his clinical course was
      uneventful and he was discharged 13 days after being admitted. CONCLUSIONS: Acute
      pancreatitis has been associated with typhoid fever. To the best of our
      knowledge, this is the youngest patient reported in the literature with this
      association. Possible pathophysiologic mechanisms are reviewed.

PMID- 11464590
TI  - [Gastrointestinal neurofibromatosis. A rare cause of abdominal surgery].
AB  - OBJECTIVE: Report two cases of gastrointestinal neurofibromatosis that required
      surgical intervention for their resolution. BACKGROUND: Neurofibromatosis is a
      congenital disease which is classified in two types. In neurofibromatosis type 1
      or Von Recklinghausen's disease the patients have some classical manifestations
      as cafe au lait pigmentation, bony abnormalities and neurofibromas of both
      peripheral and central nerves. In up to 25% of the patients with
      neurofibromatosis 1, the gastrointestinal tract is involved. The most affected
      organs are the stomach and the jejunum. The symptoms of the patients with
      gastrointestinal neurofibromatosis are related to gastrointestinal bleeding or
      obstruction. METHOD: Two patients with gastrointestinal neurofibromatosis that
      required surgical intervention for the resolution of their manifestations.
      RESULTS: Two cases of gastrointestinal neurofibromatosis, one of them had as her
      main clinical feature gastrointestinal bleeding, and the other patient intestinal
      obstruction. They were submitted to exploratory laparotomy finding
      gastrointestinal neurofibromatosis in both as the cause of their symptomatology.
      CONCLUSIONS: The management of gastrointestinal neurofibromatosis could need
      surgical intervention, and when this is done the postoperative evolution is
      satisfactory.

PMID- 11464591
TI  - [Discourse upon assuming the presidency of the Mexican Gastroenterology
      Association].

PMID- 11464593
TI  - [Cystic lymphangioma of the mesentery. Clinical, radiological, and morphological
      analysis].
AB  - BACKGROUND: The cystic mesenteric lymphangioma is a rare benign neoplasia, that
      can be misdiagnosed with others cystic intra-abdominal tumors. AIM: To shown the
      clinical and histopathological features of a cystic mesenteric lymphangioma.
      MATERIAL AND METHODS: A 17-year old male with a past history of 17 days of right
      lower abdominal pain, palpable mass, fever, nausea and vomitus. The initial
      clinical diagnosis was appendicitis, during the appendectomy a mesenteric tumor
      was found. The patient was then sent to a third level cancer center for further
      diagnosis and treatment. In an abdominal CT scan a multicystic retroperitoneal
      tumor was found and diagnosed as a cystic pancreatic tumor. At midline
      exploratory celiotomy a cystic tumor infiltrating the right colon mesenterium,
      duodenum, proximal jejunum, and pancreas head was found. A pancreatoduodenectomy
      in bloc with right hemicolectomy was performed. During the postoperative period
      the patient developed cholestasis due to endovenous parenteral nutritional
      support that improved when it was suspended. The patient was discharged without
      complications at the 15th postoperative day. The histopathologic diagnosis was
      cystic mesenteric lymphangioma. At 12 months of follow-up the patient is healthy.
      CONCLUSION: The cystic mesenteric lymphangioma is a rare benign tumor and its
      diagnosis should be included in the differential diagnosis of cystic intra
      abdominal neoplasias. Due to the tumor's location, as in the current patient, the
      surgeon should plan the appropriate surgery as to avoid morbidity, since the
      objective of such treatment is curative.

PMID- 11464594
TI  - [Prevalence of non-alcoholic steatohepatitis. Comparative study with diabetic
      patients].
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a not very well known disease;
      it has been described principally in obese and diabetic women without significant
      alcohol consumption. The women are practically asymptomatic, and the hepatic
      function test (HFT) shows minimal changes. The liver biopsy findings are
      identical to those found in alcoholic liver disease. NASH may progress to
      cirrhosis. OBJECTIVE: To determine the prevalence of NASH in a Mexican community.
      METHODS: In the City of Pachuca, Mexico, we studied volunteers of both sexes who
      were between the ages of 17 and 75 years, all with an alcohol consumption of < 20
      g/week without any known hepatic disease. A clinical review, laboratory test, and
      hepatic ultrasound were carried out. Subjects with HFT and ultrasound disorders
      were invited to continue the study with a hepatic biopsy. RESULTS: Ninety-seven
      volunteers completed the study, of whom 70 were non-diabetics and 27 were
      diabetics. Ten patients (10.3%) had NASH confirmed by hepatic biopsy; the
      prevalence in diabetics was 18.5% and in non-diabetics, 7.1%. In spite of the
      differences between NASH patients and the control group concerning gender, age,
      and diabetic status, there was no significant statistical difference except for
      the gallbladder antecedent. CONCLUSIONS: The prevalence of NASH was 10.3% in the
      studied group. NASH is more frequent in diabetics and women, but without a
      significant statistical difference. However, the odds ratio (OR) analysis shows
      diabetes and female sex to be a risk factor for NASH; therefore it is probable
      than our sample size is not large enough.

PMID- 11464595
TI  - [Synchronous neoplasias in colorectal cancer].
AB  - OBJECTIVE: The aim of this study was to show the incidence of synchronous lesions
      in colorectal cancer patients treated surgical at our service. SUMMARY BACKGROUND
      DATA: Many studies have shown different incidences of synchronous lesions in
      colorectal cancer, mainly due to variations in the accuracy of the diagnostic
      methods used and the intentional search for associated lesucosal. METHOD: Fifty
      eight clinical records of patients operated on for colorectal cancer were
      retrospectively reviewed from August 1995 to March 1999. The synchronous lesions
      were classified as benign or malignant lesions based on its histological
      classification. Statistical analysis was carried out by the Spearman coefficient
      correlation. RESULTS: Fifteen patients (25.8%) had 28 synchronous lesions, nine
      were male (60%), and six females (20%). The average age was 63.2 years with a
      range of 26 to 83 years. The endoscopic diagnosis of synchronous lesions was
      performed preoperatively in 12 patients (80%). The most frequent localization's
      of primary tumor was the sigmoid colon in six patients (40%). The more frequent
      localization of synchronous lesions was the rectum (35.7%). Benign lesions were
      most commonly found in synchronous lesions (89.3%). CONCLUSIONS: The patient with
      colorectal cancer has an unstable epithelium and an uncommon predisposition to
      develop several mucosal alterations. This predisposition is prone to grow benign
      or malignant lesions. For this reason, we advise all that patient with colorectal
      cancer be fully studied endoscopically.

PMID- 11464596
TI  - [Efficient use of the operating room].
AB  - BACKGROUND: To know whether the operating room is efficient requires continual
      evaluation of the equipment, the competency of personnel included and the level
      of complexity of the surgical procedures. This evaluation is in the institutional
      hospital center. The centers. The centers use them for internal control. However,
      they are slightly or not at all going in the productivity analysis of the
      operating room for decision making. OBJECTIVE: To identify the elements that
      favor suboptimal use of operating rooms and in each case, to propose solution for
      more efficient use. TYPE OF STUDY: Prospective, observational, transversal and
      comparative. MATERIAL AND METHODS: The study was carried out means of structured
      questionnaires with the times for surgical interventions in two operating rooms
      over sixty days. They were conducted the gynecology and general surgery areas. We
      compared real times against ideal times, and also the complexity levels.
      STATISTICAL ANALYSIS: Fisher's test p < 0.05 was considerate significant.
      RESULTS: One hundred and twenty-five surgical procedure were performed, 57.6%
      during the morning shift (MS) and 42.2% during the evening shift (ES). A total of
      66.4% corresponded to complexity level IIII, 84.8% were elective surgeries, 58.4%
      corresponded to general surgeries, and 41.6% to gynecologic surgical
      interventions. The delay in times entering the operating room was 20.5 min in MS
      compared to 4.3 min in ES p < 0.05. In more complex procedures, we found greater
      delay in surgical time. CONCLUSIONS: The efficient use of the operating room
      depends on the complying of specific functions in the programmed time of the
      surgical equipment involved, systematic supervision, and the complexity level.

PMID- 11464597
TI  - [Interstitial gastric emphysema in children].
AB  - Gastric pneumatosis is an unusual clinical finding in infants and children and it
      appears in the three following similar conditions: pneumatosis cystoides;
      emphysematous gastritis, and gastric emphysema. MATERIALS METHODS AND RESULTS:
      The clinical pictures and radiographic appearance of this association are
      described in four patients in whom the clinical course made suspect interstitial
      gastric emphysema. Two patients had hypertrophic pyloric stenosis and two,
      unspecific erosive gastritis. In the first two patients, a Fredet-Ramstedt
      procedure was performed. All patients survived. Differential diagnostic
      considerations, the importance of correct radiological diagnosis, and the results
      of proper therapy are discussed. CONCLUSIONS: Pyloric and duodenal obstruction in
      infants is the main etiologic factor in gastric emphysema.

PMID- 11464598
TI  - [Digestive tract hemorrhage secondary to jejunal angiodysplasia associated with
      jejunal diverticulosis].
AB  - The most important factor in the management of alimentary tract bleeding is the
      adequate localization of the lesion. Small bowel bleeding is a rare entity and
      determination of the specific anatomic site is difficult. Once stomach, duodenum,
      or colon origin has been discharged through endoscopy, methods such as
      angiography and Tc99m RBC scans are appropriate. We present a patient with lower
      gastrointestinal bleeding secondary to jejunal angiodysplasia associated with
      jejunal diverticular disease. In the present case, Tc99m RBC scans were used to
      identify the bleeding site. In cases of lower gastrointestinal bleeding of
      undetermined origin, we suggest the consideration of both diagnoses
      (angiodysplasia or diverticular disease) with exploratory celiotomy to resolve
      these pathologies, particularly in the elderly patient.

PMID- 11464599
TI  - [Hypochromic microcytic anemia as the only manifestation of celiac disease].
AB  - BACKGROUND: Extraintestinal symptoms and signs may be the only manifestations of
      celiac sprue. METHODS: We report a case of a patient with hypochromic microcytic
      anemia as the only expression of the disease. RESULTS: Was asymptomatic the
      patient with pallor at physical examination. The laboratory showed only
      hypochromic microcytic anemia due to iron deficiency. She was previously was
      treated twice with oral iron without achieving good results. The upper
      gastrointestinal endoscopy, the colonoscopy, and the small bowel barium contrast
      study were normal. The small bowel biopsy showed villous atrophy and a chronic
      inflammatory infiltrate of the lamina propria. The antiendomysial and
      antireticulin antibodies were negative. The IgA antigliadin antibody was positive
      (1:120). The patient was initiated on a gluten free diet and oral iron. After
      four months of treatment, hemoglobin and the iron serum levels were normal and at
      6 months, the small bowel biopsy showed striking improvement. CONCLUSIONS:
      Familiarity with the diverse extraintestinal features of celiac sprue and a high
      index of suspicion are essential for accurate diagnosis in patients with subtle
      presentations.

PMID- 11464601
TI  - [Colonoscopy. Analysis of 2,000 procedures].
AB  - BACKGROUND: During the last 3 decades, colonoscopy has become the diagnostic
      study with greatest sensitivity and acuity in colonic pathology. AIMS: To know
      the most frequent diagnostic and colonoscopic disorders, and the pathology found,
      to establish certainty of the colonoscopic procedure. METHOD: Between 1987 and
      1997, a descriptive, transversal, retrospective and observational study of the
      2,000 colonoscopies that were carried out at on service was done, making a
      registry of the endoscopic search in colorectal pathology and their
      characteristics in on patients. RESULTS: Colonoscopies were done in 967 men
      (47.3%) and 1,053 women (52.6%) with a median age of 55.8 years (10 range (-) 93
      years). In 1,780 of them (89.%), it was possible to arrive to cecum; 1,150
      (57.5%) were pathologic. The most frequent finding was hemorrhage of the lower
      digestive tube in 525 (26.2%) patients; in addition cancer in 402 (20.1%),
      suspicion of intestinal inflammatory disease 292 (14.6%) and colorectal polyps
      199 (10%) were found. The most frequent endoscopic diagnosis was colorectal
      polyps in 405 (35.7%) patients; in additions diverticular disease was found in
      404 (35.1%) patients intestinal inflammatory disease in 185 (16%), colorectal
      cancer in 85 (7.4%), and vascular ectasias in 52 (4.5%) patients. There were four
      complicated cases (0.25%), three by resolved therapeutic colonoscopy and one
      diagnostically. CONCLUSION: The most frequent colonoscopic were findings
      hemorrhage of the lower digestive tube and the finding of cancer. The most
      frequent diagnoses were colorectal polyps and diverticular disease. Colonoscopy
      is a safe diagnostic and therapeutic procedure.

PMID- 11464602
TI  - [Indications and results of hepatic resection in benign and malignant tumors].
AB  - OBJECTIVE: The authors analyze the indications and results in 75 consecutive
      liver resections. BACKGROUND: In recent years, the morbidity and mortality of
      this procedure have been reduced at specialized centers due to better control of
      intraoperative bleeding and improved perioperative management. METHODS: The
      clinical records of 72 patients who had a liver resection over a 4-year period
      were reviewed. RESULTS: Fifty-two were females and 23, males. Ages ranged between
      15 and 88 years (X: 50 +/- 22 years). The indications for surgery were liver,
      secondary in 28, gallbladder or bile duct cancer in 17, benign liver tumors in
      16, and primary malignant liver tumors in 14. Forty-seven major liver resections
      were performed and included 25 right hepatectomies, 13 left hepatectomies, five
      right trisegmentectomies, and four left trisegmentectomies. Additionally, 28
      minor resections included 12 resections of the left lateral segment, nine
      bisegmentectomies, five segmentectomies and two resections of the caudate lobe.
      Operative time ranged from 60-540 min (X: 260 +/- 97 min); the mean operative
      bleeding was 1439 +/- 660 mL (range 20-5,000 mL). The pringle maneuver was used
      in 63 patients and ranged from 20-100 min (X: 42 +/- 25 min). Twenty-five
      patients presented complications (33%), the most frequent being hepatic failure,
      postoperative bleeding, ascitis and bilomas. Six patients died (8%) due to
      hepatic and multiorganic failure in four pneumonia and myocardial infarct in one,
      and systemic sepsis in the other. CONCLUSIONS: Liver resection is an excellent
      therapeutic alternative in patients with benign and malignant liver focal
      lesions.

PMID- 11464603
TI  - [Neutropenic enteropathy associated with autoimmune diseases. A more aggressive
      presentation].
AB  - BACKGROUND: There is just one case report dealing with neutropenic enteropathy
      associated with autoimmune diseases. METHOD: An autopsy analysis of neutropenic
      enteropathy in autoimmune and hematologic diseases was carried on. Gross findings
      and slides were reviewed. A blind analysis is of the mucosal lesions in small and
      large intestine as well as of the clinical course was made. RESULTS: Seventeen
      cases of neutropenic enteropathy were found a once period of 13 years (1,068
      autopsies). Fourteen cases were seen in patients with hematologic diseases and
      three in patients with autoimmune diseases. Acute symptoms had a 6-day evolution
      and were characterized by abdominal pain, diarrhea, ascitis, and fever in
      autoimmune diseases. Extension of colonic damage was 58 and 13% in small bowel.
      Cases associated with hematologic diseases had longer clinical course with fever
      abdominal pain and colonic lesions in 21% of the surface and small bowel lesions
      in 6% of the mucosa. No acute inflammatory infiltrate around the necrotic zones
      was observed in either group Azathioprine, steroids, methotrexate, and alkylating
      agents were associated to neutropenia. CONCLUSIONS: Clinical evolution and
      morphologic findings were more severe in neutropenic enteropathy associated with
      autoimmune diseases than in patients with hematologic diseases.

PMID- 11464604
TI  - [Causes and mortality of intestinal obstruction in the elderly].
AB  - OBJECTIVE: To determine the etiology, clinical symptom, evolution, and results of
      management of small bowel obstruction (SBO) in our geriatric patients.
      BACKGROUND: SBO is one of the first etiologies of surgical emergency procedures
      in the elderly with mortality at 20-40%. It is believed that etiology of these
      obstructions is due to the abdominal hernia adherence and oncologic problems.
      METHOD: In all patients older than 65 year of age, no traumatic, attending the
      emergency room of our General Surgery Service from December 1996 to June 1998,
      data concerning symptomatology and surgical finding were collected. RESULTS: In
      104 surgical elderly emergency patients, 40 cases was operated on by BO. The
      first cause was inguinal and umbilical hernia (35%). The first symptom was
      hypertympanism and radiological data. Mortality was 37% conditioned by metabolic
      and pneumonic problems. CONCLUSIONS: The abdominal hernias were the firth
      etiology from SBO. We recommended immediate surgery and preoperative correction
      of the additional diseases.

PMID- 11464605
TI  - [Hamartoma of the bile ducts. Report of a case and review of the literature].
AB  - OBJECTIVE: A clinical case report and literature review of the on the biliary
      duct hamartoma is presented. BACKGROUND: The biliary hamartoma is a rare hepatic
      lesion described for the first time in 1918 by Von Meyenburg. It is consistent
      with biliary duct deformity and disorganization, forming cystic structures
      varying in sizes. METHODS: The patient is a 44-year-old female who had an
      ultrasonogram that showing disseminated hepatic lesions, which rendered an
      irregular shape to the viscera. An abdominal CT scan corroborated this hepatic
      lesion that appeared as multiple and low density in cystic form, disseminated
      through the entire organ. This study also showed a pelvic lesion in the left
      ligament of the uterus. The images were interpreted as malignant left ovaric
      tumor with hepatic metastases. The patient was taken to exploratory laparotomy.
      Liver biopsies and radical hysterectomy were performed. RESULTS: The frozen
      sections were reported as negative for malignancy and definitive diagnostic was
      biliary duct hamartoma and uterine myomatosis. CONCLUSIONS: The presence of
      biliary duct hamartoma causes diagnostic confusion and difficulty in the
      management of patients in that it appears to be liver metastases.

PMID- 11464606
TI  - [Pancreatic pseudocyst, Torulopsis glabrata primary infection. Report of a case].
AB  - BACKGROUND: T. glabrata is a saprophyte fungus that has been considered in the
      past years to be a pathologic agent in the pancreatic pseudocyst. Only three
      cases have been reported in the world literature. OBJECTIVE: To present a new
      case of a patient with pancreatic pseudocyst whose primary cause of infection and
      sepsis was Torulopsis glabrata and to analyze the possible factors that produced
      the infection. In the same manner, a review of the cases on literature to date
      was conducted. CASE REPORT: We present the clinical evolution of a post surgical
      patient with conventional cholecystectomy with biliary duct exploration and
      biliary duct derivation secondary to choledocholithiasis. This patient developed
      acute pancreatitis days after an endoscopic retrograde cholangiopancreatography
      was carried out. The patient received wide-range antibiotics and total parenteral
      nutrition (TPN). Later, the patient's case was complicated with pancreatic
      pseudocyst that was act diagnosed and managed initially with antifungus therapy
      due to an asymptomatic stage and a late report for T. glabrata. CONCLUSIONS:
      Pancreatobiliary duct instrumentation, in the same manner, prolonged therapy with
      wide-spectrum antibiotics and with TPN an with the means that had associated as
      risk factors for T. glabrata infection. Therefore, this fungus could have changed
      its biologic behavior from commensal to pathogenic. A potentially pathogenic
      agent in patients receiving this type of therapy and who have pancreatic
      pseudocyst must be considered to recognize these in the initial stages and begin
      therapy.

PMID- 11464607
TI  - [Acute mesenteric ischemia. Profile of an aggressive disease].
AB  - Acute mesenteric ischemia is an abdominal emergency due to inadequate tissue
      perfusion with a mortality rate between 60 and 100%. Intestinal damage by
      ischemia depends on general circulation, collateral blood flow, response of the
      mesenteric vasculature to autonomic stimuli, circulating vasoactive substances,
      local humoral factors, and the normal and abnormal products of cellular
      metabolism before and after reperfusion of the ischemic segment. Four
      physiopathologic phenomenon are present: superior mesenteric artery embolism;
      superior mesenteric artery thrombosis; non-occlusive acute mesenteric ischemia,
      and superior mesenteric venous thrombosis; embolism event is the most frequent.
      The injury observed after 3 of ischemia (blood flow reduced to 20% of normal) and
      1 of reperfusion is more severe than 4 of ischemia. Clinical diagnosis of
      mesenteric ischemia required a high suspect index, specially in elderly patients
      with cardiovascular problems. Abdominal pain and hemodynamic and/or metabolic
      changes are the most frequent symptoms. Although some authors have questioned the
      need for angiography, this study is the key not only to making a diagnosis of
      acute mesenteric ischemia before bowel infarction and prior to laparotomy, but
      also to initiate intra-arterial mesenteric angiography therapy with vasodilators.
      Patients who persist with acute abdomen will require exploratory celiotomy and
      vascular exploration. The outcome depends on early diagnosis and therapy to avoid
      ischemia progression and reperfusion injury.

PMID- 11464608
TI  - [Anorectal surgery in patients infected with human immunodeficiency virus].
AB  - OBJECTIVE: The aim of this study was to describe the clinical characteristics of
      the patients infected with the human immunodeficiency virus (HIV), who were
      submitted to anorectal surgery with emphasis on healing time and complications.
      METHODS: The patients were evaluated prospectively from July 1998 to July 1999;
      there was a total of 23 patients HIV (+) (Group 1). They were compared to a
      control group of randomly chosen HIV (-) patients (Group II) to establish the
      characteristics of each group, the morbidity, and the time of healing. The
      statistical analysis was performed with the student T test. RESULTS: In Group I,
      the diagnosis were fistula in the anus, anal fissure, anal abscess, condylomata
      acuminata, anal ulcer, and cutaneous flaps. Seven patients had a fistulotomy, a
      drainage of abscess in one, resection of different skin lesions in 12,
      electrofulguration of condylomata in two, fisturectomy in three and solely biopsy
      in three. The average healing time was 26.087 days for Group I and 23.21 days for
      Group II. A comparison between healing time and complications in these two groups
      was carried out to determine a whether significant difference exists in these
      parameters. There was no significant difference between these groups, but there
      were unequal rates of healing (26.087, DE +/- 10.778 days vs 23.21 DE +/- 6.259
      days; p = not significant) and complications for the similar procedures.
      CONCLUSIONS: The healing in time HIV (+) patients submitted to anorectal surgery
      may not vary important when compared with HIV (-) patients.

PMID- 11464609
TI  - [Incidence and relation of endoscopic sphincterotomy to the proximal migration of
      biliary prostheses].
AB  - BACKGROUND: Endoprostheses are commonly used in the treatment of biliary
      disorders. The frequency of and potential risk factors for stent migration,
      however, remain largely unknown. OBJECTIVE: To determine how often biliary duct
      stents migrate proximally and to quantify the influence of specific risk factors
      on the occurrence of stent migration. PATIENTS METHODS AND RESULTS: We analyzed
      the occurrence of stent migration among the 410 stents for which follow-up data
      were available between January 1995 to December 1998. In 272 cases, we performed
      endoscopic sphincterotomy. Results demonstrated incidence rates of 4.4% for
      proximal biliary stent migration iatrogenic strictures were significantly
      associated with proximal biliary stent migration. CONCLUSIONS: Iatrogenic
      strictures were significantly associated with proximal common bile duct migration
      and the association between sphincterotomy and proximal migration failed to reach
      statistical significance.

PMID- 11464610
TI  - [Laparoscopically created stomas].
AB  - PURPOSE: The aim of this paper is to present the results obtained in five cases
      with a stoma created by the laparoscopic approach. PATIENTS AND METHOD: Analysis
      of five patients who required a stoma as treatment for their diseases or as a
      complementary management of another medical problem from March 1999 to May 1999.
      There were three women and two men. Mean age was 43 years (range 20-59 years).
      Two women had a rectovaginal fistula secondary to radiation proctitis, another
      woman presented an infected sacral wound, one man suffered a sphincteric lesion
      that required sphincteroplasty, and the other man had Fournier's gangrene.
      Surgical technique included the use of two ports, one at the umbilicus for the
      camera and the other at the site previously chosen for the stoma. RESULTS: Mean
      surgical time was 30 min (range 20-40 min), transoperative bleeding was
      meaningless; all stomas began to function during the first 24 h after the
      procedure. One patient began oral intake on the first day, three patients on the
      second day, and one patient was intubated in the intensive care unit and for this
      reason was unable to eat. All stomas achieved the objective sought and there were
      no complications related to the procedure. CONCLUSIONS: Stoma creation by the
      laparoscopic approach may offer advantages over the open-surgery technique.

PMID- 11464611
TI  - [Pneumatosis intestinalis. Report of 3 cases].
AB  - OBJECTIVE: To describe the clinical, radiological, morphological, and
      immunohistochemical characteristics of three cases of pneumatosis intestinalis.
      METHODS: From 1982 to 1999, cases diagnosed as pneumatosis cystoides intestinalis
      were reviewed. The laboratory results, X-ray findings, clinical course, treatment
      and evolution were obtained from the clinical charts. Slides and macroscopic
      photos were obtained from the surgical pathology files. New slides were obtained
      from the paraffin blocks for immunohistochemical detection of endothelial cells
      (CD 31) and macrophagic cells (CD 68). RESULTS: We found three patients with
      pneumatosis intestinalis associated to a history of abdominal surgeries from 936
      enteral resections (0.3%). These three patients showed clinical features of
      intestinal obstruction. Morphological and immunohistochemical analysis showed
      pseudocysts without an epithelial and endothelial lining. Some spaces were lined
      by multinucleated giant cells positive for CD 68 and endothelial cells that were
      CD 31 positive. CONCLUSIONS: Antecedent of obstruction and abdominal surgeries
      were the constant association with pneumatosis cystoides intestinalis. Most
      lesions were pseudocysts without epithelial or endothelial lining.

PMID- 11464612
TI  - [Hirschsprung disease in the adult. Report of a case].
AB  - OBJECTIVE: To describe a case of Hirschsprung's disease (HD) in an adult patient.
      BACKGROUND: HD is diagnosed in the newborn in 80 to 90% of cases. HD is rare in
      the adult, and usually affects an ultrashort segment of the bowel. CASE REPORT: A
      49-year-old woman with a history of constipation since birth is involved. She was
      submitted to an abdominal laparotomy because of fecal impaction. A colostomy was
      performed. The diagnosis of HD affecting, the descending colon was established
      with manometry and histopathology. She underwent surgery, and a proctectomy and
      left hemicolectomy with colo-anal anastomosis was performed. CONCLUSION: Adult HD
      is an infrequently diagnosed entity that must be suspected in a patient with
      chronic, intractable constipation from infancy, evidence of megacolon, and
      typical manometric and histopathologic features. The short and ultrashort-segment
      disease are more often found in older children and adults. The differential
      diagnosis includes idiopathic megarectum, functional constipation, and colonic
      pseudo-obstruction.

PMID- 11464613
TI  - [Primary lipoma of the liver].
AB  - A case of lipoma of the liver is reported in a 57-year-old woman with a 10-month
      history of non-insulin dependent diabetes mellitus and 3 days with abdominal
      pain, distention, nausea, and vomiting. On medical examination, the liver was
      palpable 5 cm below the right costal margin without splenomegaly or ascites. A CT
      scan revealed a well-defined fat attenuation tumor and an MR demonstrated a well
      circumscribed lesion with bright signal intensity. An extended right hepatic
      lobectomy was performed. The resected specimen measured 28.6 x 18.3 x 8.2 cm and
      weighed 2,200 g. The yellow and well-circumscribed tumor measured 15 x 9.5 cm and
      was composed of mature adipose cells pushing the liver tissue at the periphery.
      The patient was asymptomatic 6 months after surgery.

PMID- 11464614
TI  - [Massive hepatobiliary fascioliasis].
AB  - Massive hepatobiliary fascioliasis. Report of two cases. INTRODUCTION: Liver
      fascioliasis is the most frequent parasitic disease of the biliary tract in
      Mexico. Massive infestation is common in sheep and bovines and rarely occurs in
      humans. Only two previous cases of massive fascioliasis has been reported and we
      present here in two additional cases. Case reports. Both cases presented in
      alcohol-related liver disease patients who had eaten watercress Nasturium
      officinalis. Upper abdominal pain, obstructive jaundice, and choledochal
      dilatation were the salient manifestations. Diagnosis was made by surgical
      exploration and adult fluke identification. One patient died due to progressive
      liver failure and the other, is alive and received praziquantel treatment.
      CONCLUSIONS: Since 1935, approximately fifty cases of massive hepatobiliary
      fascioliasis have been reported in Mexico, most misdiagnosed as cholelithiasis;
      however, a history of watercress ingestion has been recorded in most of these
      cases.

PMID- 11464615
TI  - [Editorial comment on the article: Incidence and relation of endoscopic
      sphincterotomy to the proximal migration of biliary prostheses].

PMID- 11464616
TI  - [Comment on the article: Laparoscopically created stomas].

PMID- 11464617
TI  - [Epidemiologic and clinical aspects of Helicobacter pylori infection in
      children].
AB  - Worldwide, H. pylori prevalence in children ranges from under 10% to almost 80%.
      Prevalence is low in developed countries; whereas high prevalence is observed in
      most developing countries. Documented risk factors for infection include
      socioeconomic status, household crowding, ethnicity, migration from high
      prevalence regions, and infection status of family members. H. pylori infection
      is not associated with specific symptoms in children; although it is consistently
      associated with antral gastritis, which clinical significance is unclear. H.
      pylori associated duodenal ulcers are seldom seen in children under 10 years of
      age. The role of the infection in recurrent abdominal pain is highly
      controversial. H. pylori-infected children demonstrate a chronic inflammatory
      cell infiltrate, with a lack neutrophils, as compared with the response observed
      in adults. The importance of virulence determinants such as cagA and vacA,
      described as relevant for disease during H. pylori infection, has not been
      extensively studied in children. Sensitive and specific methods for the detection
      of H. pylori in children are needed, especially in infant populations where the
      colonization is in its early phases. Non-invasive, cheap, and simple methods are
      needed for epidemiologic studies. There is no consensus about criteria for the
      use of eradication treatment in H. pylori-infected children. Multicenter
      pediatric studies are needed to solve the many unanswered question on the natural
      history of H. pylori infection in children, including identification of risk
      factors for infection, identification of prognostic indicators for the
      development of gastroduodenal disease later in life, and the host response to
      infection.

PMID- 11464618
TI  - [The association between Helicobacter pylori and gastric neoplasia. Epidemiologic
      evidence].
AB  - Helicobacter pylori (HP) causes chronic gastritis and, together with non
      steroidal anti-inflammatory drugs, is considered the most frequent etiologic
      agent of peptic ulcer. Since there are numerous epidemiologic and pathogenesis
      studies that demonstrate an association between infection by HP and gastric
      neoplasias, the World Health Organization declared, in 1994, HP infection a Group
      1 carcinogen (a definitive cause of human neoplasias, similar to tobacco). This
      article reviews the epidemiological evidence supporting the association between
      HP infection and two gastric neoplasias: adenocarcinoma and B cell lymphoma
      associated to mucosas (MALT). This article also presents preliminary results of a
      project performed in the mountainous region of Chiapas, Mexico, in which the
      decrease of precancerous gastric lesions were studied one year after treatment
      for HP infection.

PMID- 11464619
TI  - [Importance of Helicobacter pylori in the pathogenesis of gastric cancer.
      Experimental models in rodents].
AB  - We found that the seroprevalence in Cancer Institute of H. pylori infection was
      significantly more frequent in gastric cancer than in age- and gender-matched
      controls. This study suggested an epidemiological link between H. pylori
      infection and gastric cancer. H. pylori exhibits a complex system of enzymes
      which serve a range of functions. Toxic effects are produced by urease (UR),
      phospholipase (PL) and alcohol dehydrogenase (ADH). We embarked on an exploration
      of the enzyme activities of H. pylori infected patients using a TLC
      autoradioluminography. This method has a wide dynamic range and could offer an
      analytical technique for studying a radioactive compound and its enzymes in H.
      pylori infected mucosa. Biopsies samples taken from 21 gastric cancer patients
      and 95 controls were studied. Although high activity of UR indicates well the
      presence of H. pylori impairment, activities of ADH and PL reflects more the
      chronicity of mucosal damage in both groups. Clearly, the enzyme profile showed
      in our study reflects the "physiological" adaptations behind chronic injured
      mucosal changes but its relation to gastric cancer and H. pylori needs further
      study. There is an urgent need to understand the carcinogenesis process using
      animal models. We performed previous study for to explore the effect of H. pylori
      infection on N- methyl-N-nitrosourea-induced (MNU) gastric carcinogenesis in mice
      C57BL/6 mice were administered broth culture of H. pylori and given MNU in
      drinking water. In terms of the incidence of neoplasms development was increase
      in the MNU group pre-infected with H. pylori. That findings showed that C57BL/6
      mice-infected model is well suited for investigating the bacteria promoter effect
      in the gastric carcinogenesis. Finally another rodent model study (still in
      process) showed rapid development of hyperplastic gastritis with gastric erosions
      in H. pylori-infected MTH1 knockout mice. We sought to further evaluate MTH1
      knockout mice as potential test animal for carcinogenesis. CONCLUSION: It is
      suggested that H. pylori infection is an important risk factor for the
      development of gastric cancer. The possibility that this organism acts
      etiologically, exerting its effect over long period of time, is biologically
      plausible. However, the role of H. pylori per se in that process is still a
      matter of discussion. The various enzymes of H. pylori discussed in this paper
      support colonization, and are perhaps important for epithelial damage, they could
      contribute to the stimulation and modulation of the chronic inflammatory
      response, but its relation to gastric cancer and H. pylori needs further study.
      Finally H. pylori in C57BL/6 and knockout mice showed excellent colonization at
      two months and six months after infection there was adenomatous, hyperplastic and
      ulcerative changes. Those findings showed that both mice-infected models are well
      suited for investigating the bacteria promoter effect in the gastric
      carcinogenesis.

PMID- 11464620
TI  - [Helicobacter pylori. Its relationships and morphological controversies].
AB  - After Helicobacter pylori was described in 1984, it has been related to numerous
      benign and malignant morphological disturbances. The distribution of the
      gastroduodenal disease, their histological expressions and their controversial
      topics regarding their relationship with HP are better known today. The aim of
      this paper is review some of these features.

PMID- 11464621
TI  - [Peptic ulcer and Helicobacter pyrlori. Results and consequences of its
      eradication].
AB  - Helicobacter pylori (Hp) a known pathogen of peptic ulcer disease (PUD), causes
      more than 90% of them when non steroidal anti-inflammatory agents (NSAID) are
      excluded. Prevalence of Hp is greater than 70% within some underdeveloped
      societies, but yet less than 1% suffer PUD. Such selectivity has been attributed
      to pathogenic differences of diverse Hp strains, their relative proportion in a
      given patient, but also to genetic host factors that favors colonization and
      different immunologic responses that end up in PUD in some, while gastritis is
      the only consequence in others. Other pathophysiologic factors, independent of Hp
      such as acid hypersecretion or duodenal bicarbonate hyposecretion may interplay
      with Hp to provoke PUD. Pepsinogen I levels are better predictors of PUD than Hp
      is in a given individual. PUD recurrence is less than 2% per year, although some
      controversies prevail whether Hp should be eradicated in patients requiring
      NSAID, since eradication does not prevent PUD, does not improves healing of
      existing ulcers nor decreases risk of bleeding. Even though, bleeding recurrence
      is less frequent when Hp has been treated. Prevalence of Hp is quite similar in
      bleeding PUD to that of general population of a given geographic area, Hp it is
      not a risk factor for this complication. Hp eradication in PUD causes reflux
      esophagitis in 25% of patients, and reflux medical control is far more difficult.
      Even worse hypergastrinemia produced by antisecretory agents is further increased
      under Hp infection, and their use over 1 year is accompanied by ECL hyperplasia
      in 30% of them. Thus Hp interplay and consequences are diverse and complex. Their
      knowledge is needed for proper selection of patients that need eradication.

PMID- 11464622
TI  - [Treatment of Helicobacter pylori infection. Whom to treat and with what?].
AB  - Actually is considered that Helicobacter pylori play a major role in the genesis
      of peptic ulcer. Like in the gastric and duodenal ulcer. When we demonstrate the
      presence of Helicobacter pylori in the gastric antrum of patients with ulcer they
      must receive eradication treatment. Another indication for eradication treatment
      are the patients with malt lymphoma or patients with endoscopical resection of
      gastric carcinoma. The ideal treatment is the therapy that eradicate 90% of the
      cases. The most effective are the triple therapies with one proton pump inhibitor
      with two antibiotics like amoxycillin plus clarithromycin. In Mexico the
      therapies with metronidazole are not recommended because we have high rates of
      resistance to this drug 70%. Is not justified to treat patients with non ulcer
      dyspepsia. We still recommended the schemes of 14 days. A good alternative is the
      combination of ranitidine bismuth citrate plus two antibiotics. Is possible that
      in the future we can have a vaccine to eradicate and to prevent the infection.

PMID- 11464624
TI  - [Early gastric carcinoma. Analysis of 21 cases].
AB  - BACKGROUND: Early gastric carcinoma (EGC) is defined as a neoplasm confined to
      the mucosa and submucosa regardless of the presence of metastasis. This lesion is
      found in approximately 3% of cases in Mexico. The aim of this study is to
      describe our experience with EGC, emphasizing early detection as the most useful
      method to decrease mortality. METHODS: Retrospective review of records of
      patients with EGC treated at an oncologic referral center over a 12-years period.
      RESULTS: Twenty-one cases of EGC were retrieved. Mean age was 58.1 years (range,
      33 to 84). Twelve were women and nine, men. Lymph node or distant metastasis were
      not found. Overall 5-year survival was 66.4%. Twenty patients underwent radical
      gastrectomy and only one underwent wedge resection of the gastric wall. Two
      patients (9.5%) presented recurrence and cancer-related death. Mean follow-up was
      8.3 years. CONCLUSION: The prognosis of EGC in our hospital is lower than in
      countries other than Mexico and this lesion is found with low frequency.
      Increasing the detection EGC is the best method to reduce GC-related mortality.

PMID- 11464623
TI  - [Is the association of Helicobacter pylori with humans a classical example of
      parasitism?].
AB  - Since the first report of the potential role of Helicobacter pylori as cause of
      disease of the upper intestinal tract of humans, a major controversial has
      developed. First, the role of H. pylori as the etiological agent of duodenal and
      gastric ulcer has been questioned. Second, the possibility of H. pylori as a
      major risk factor in the development of distal gastric cancer has not been fully
      accepted. It is interesting that at the time when the etiological role of H.
      pylori is almost universally accepted, series of publications have suggested that
      the elimination of H. pylori from asymptomatic individuals might represent a risk
      for the development of other upper gastrointestinal diseases such as GERD and
      cancer of the esophagus. The main goal of this revision is to describe the
      virulence factors associated with H. pylori as well as its interaction with the
      human host, to establish whether H. pylori should be considered a true pathogen
      or only a commensal.

PMID- 11464625
TI  - [Proximal migration of biliary prosthesis. Endoscopic extraction techniques].
AB  - BACKGROUND: Proximal migration of a biliary stent is an uncommon event, but its
      management can present a technical challenge to the therapeutic endoscopist.
      OBJECTIVE: We reviewed the methods that have been used for retrieval of
      proximally migrated biliary stents in a referral endoscopic center. PATIENTS
      METHOD, AND RESULTS: From January 1995 to December 1998, there were 410
      procedures for insertion of biliary stents. Eighteen patients had migrated
      biliary stents; 15 stents (83%) were extracted successfully. One half of the
      stents were retrieved by grasping the stent directly with a wire basket. Four
      were recovered using the Soehendra device, and a stone retrieval balloon
      alongside the stents to provide traction indirectly in two patients. Surgical
      techniques were necessary in three cases. CONCLUSIONS: In patients with a dilated
      duct, indirect traction with a balloon or direct grasping of the stent with a
      wire basket is usually successful. Cannulating the stent lumen with a wire is
      often the best approach in patients with biliary stricture or nondilated duct.
      Using these techniques, most proximally migrated biliary stents can be retrieved
      endoscopically.

PMID- 11464626
TI  - [Preservation of hepatocytes in UW and HTK solutions with added fluorocarbons].
AB  - BACKGROUND: One of the limitations for hepatocyte transplantation is the short
      survival of isolated hepatocytes. OBJECTIVE: We evaluated the utility of
      fluorocarbons (PFC) added to University of Wisconsin (UW) and histidine
      tryptofane-ketoglutarate (HTK) solutions on hepatocyte preservation. METHOD: Rat
      hepatocytes were isolated by colagenase digestion technique, with a viability
      greater than 85% measured by tripan blue exclusion. We suspended 1.2 x 10(8)
      hepatocytes in 20 mL of: HTK solution, HTK with perfluor-n-octane (HTK + PFC), UW
      solution, and E. Williams medium as control group (CG). Five samples of each
      group were stored at 4 degrees C for 40 h. We measured Cell viability, large
      membrane bleb formation and extracellular LDH at 0, 12, 24 and 36 hours. RESULTS:
      Cell viability was lower in the UW at 12 h (p < 0.05) and 24 h (p < 0.05)
      compared to the rest of the study groups; at 36 h we found no differences in cell
      viability. There were fewer hepatocytes with large membrane blebs in UW + PFC;
      compared with the remainder of the solutions, but this difference was only
      reached statistical significance when compared to UW at 24 h (p < 0.05) and at 36
      h (p < 0.05). When comparing groups with or without fluorocarbons LDH levels
      showed no difference at 0, 12, 24, and 36 h. CONCLUSIONS: The present study shows
      that the addition of fluorocarbons to UW solution diminishes large membrane
      formation (irreversible damage) and improves cell viability at 12 and 24 h.
      However, fluorocarbons added to both solutions failed to increase preservation
      time beyond 24 h.

PMID- 11464627
TI  - [677T mutation of the MTHFR gene in adenomas and colorectal cancer in a
      population sample from the Northeastern Mexico. Preliminary results].
AB  - INTRODUCTION: Adequate intake of folates has been associated to low prevalence of
      colon cancer. Methylenetetrahydrofolate reductase enzyme (MTHFR) plays an
      important role in folate metabolism. The role of the 677 mutation at the MTHFR
      gene in the risk for colorectal cancer remains controversial. A recent report
      established that this mutation has a high prevalence in the healthy Mexican
      population. AIMS: To analyze the prevalence of 677T MTHFR mutation in patients
      with colorectal cancer and controls without chronic gastrointestinal disorders.
      METHODS: Seventy-four colorectal cancer, 32 adenomas and 110 normal samples were
      analyzed. Patients and controls were matched for sex and age. For each sample,
      DNA isolation, PCR, and mutation detection by restriction enzyme digestion were
      performed to determine the allele at the 677 position in the MTHFR gene. RESULTS:
      Genotype 677C/677C was found in 18.7, 20.3, and 30.9% in adenomas, cancer lesions
      and controls, respectively. Frequencies of the 677C/677T genotype were 59.4,
      56.7, and 47.3%, in adenomas, cancer lesions, and controls, respectively.
      Genotype 677T/677T was found in 21.9, 23.0, and 21.8% in adenomas, cancer
      lesions, and controls, respectively. The odds ratio between genotypes carrying
      the mutation (T/T and C/T) and normal genotype (CC) was 1.81 (IC 95% 0.97-3.3),
      chi 2 = 3.5, p = 0.06. CONCLUSION: Our results showed that persons who carry the
      677T mutation at MTHFR locus have a tendency for an increased risk for colorectal
      cancer. This study supports the basic concept that low levels of folic acid
      contribute with the colorectal cancer pathogenesis. Our lack of statistic
      significance may be due to reduced sample size.

PMID- 11464628
TI  - [Wilson disease. Report of a case of autopsy with copper tissue quantification
      and electronic microscopy].
AB  - Wilson's disease is a rare autosomal recessive disorder of copper metabolism.
      Kinnear Wilson described the entity in 1912 and considered it to be a
      degenerative disorder of the central nervous system associated with asymptomatic
      cirrhosis. Gene linkage analysis has localized the genetic defect on chromosome
      13. CLINICAL CASE: Woman of 15 years of age. She began with amenorrhea at 8
      months of evolution, and acholia and hepatomegaly 1 month before her death. The
      viral serology panel was negative. She evolved with severe hepatic insufficiency
      and died. The quantitation of copper dose postmortem in hepatic tissue by atomic
      absorption spectrophotometry resulted in 250.57 micrograms/g. Electronic
      microscopy showed dense bodies in the mitochondria. Young adolescents frequently
      develop hepatic insufficiency as a first manifestation of Wilson's disease.
      Histologically, some morphology data such as the glucogenized naked nuclei,
      microvesticular fatty change, Mallory bodies, and hepatic regeneration, but the
      definitive diagnosis was decreased serum ceruloplasmin level, quantitation of
      copper in tissue, electron microscopy, and more recently, the molecular biology
      or genetic alterations.

PMID- 11464629
TI  - [Diagnostic and therapeutic endoscopic cholangiopancreatography in biliary leak
      after liver transplantation. Report of 2 cases].
AB  - BACKGROUND: The most common biliary tract complications after orthotopic liver
      transplantation are anastomotic strictures and bile leaks. These remain important
      causes of morbidity, frequently prompting surgical approach and/or biliary
      drainage. OBJECTIVE: To report our experience using endoscopic retrograde
      cholangiopancreatography (ERCP) in the diagnosis and management of biliary tract
      complications in patients with hepatic transplantation. PATIENTS/METHODS AND
      RESULTS: We present two patients with hepatic transplantation who developed bile
      peritonitis secondary to biliary leaks diagnosed by ERCP, both treated with
      sphincterotomy and biliary endoprostheses. Bile leaks rapidly resolved after
      endoscopic sphincterotomy and stent placement. CONCLUSIONS: ERCP is a useful
      diagnostic and therapeutic intervention for post-transplantation biliary tract
      complications.

PMID- 11464630
TI  - [Nesidioblastosis as extracolonic manifestation associated with adenomatous
      familial polyposis].
AB  - OBJECTIVE: To describe the case of a patient with familial adenomatous polyposis
      (FAP) who developed organic hyperinsulinemia and hypoglycemia due to pancreatic
      nesidioblastosis. BACKGROUND: FAP can be considered as one of the familial cancer
      syndromes. The development of endocrine tumors in these patients is an infrequent
      event, and most of these tumors have been well-differentiated thyroid neoplasms.
      To our knowledge, the occurrence of organic hyperinsulinemia in the context of
      FAP has not been reported. METHODS: Organic hyperinsulinemia was demonstrated
      during a 72-h fast, measuring insulin and C-peptide by RIA at the time of
      hypoglycemia. Immunohistochemistry for insulin and other pancreatic hormones was
      performed on the surgical pancreatic specimen. RESULTS: The patient underwent a
      distal pancreatectomy with resolution of hypoglycemia. Histopathologically, the
      excised pancreas showed beta cell hyperplasia arising from the ductal epithelium.
      Such beta cells strongly immunostained for insulin, pancreatic polypeptide, and
      neuron-specific enolase. CONCLUSIONS: The development of endocrine tumors in an
      inherited cancer syndromes such as FAP is rare. Such an association may suggest
      shared mechanisms of tumorigenesis. The case herein reported should prompt us to
      consider organic hyperinsulinism as an extracolonic manifestation of FAP.

PMID- 11464631
TI  - [Laparoscopic partial hepatectomy. Report of the first case in Mexico].
AB  - The authors report the case of a 47-year-old female patient referred to the
      Instituto Nacional de Cancerologia with abdominal pain and a focal liver lesion
      in the left lateral segment. After a careful tumor work-up, a laparoscopic left
      lateral segmentectomy was performed. The postoperative course was uneventful and
      the patient was discharged at the 2nd postoperative day. Histologic examination
      revealed focal nodular hyperplasia. In a search of the literature we find this to
      be the first case treated by this approach in Mexico.

PMID- 11464632
TI  - [The astonishing evolution of endoscopy].

PMID- 11464633
TI  - [Prognostic index in wound infection and abdominal sepsis].
AB  - OBJECTIVE: To establish an abdominal surgical infection prognostic index with all
      risk factors. SUMMARY BACKGROUND DATA: Individuals, requiring abdominal surgery
      have an established surgical infection risk of 1% and this risk increases with
      several factors, such as age over 50 years, (4%), diabetes mellitus (12%),
      obesity (8%), hospitalization up to 10 days (4%), bad nutrition (2%), surgical
      time up to 3 h (6%) summer (4%) shock (6%) immunosuppression (6%), contaminated
      surgery (from 1%-40%), or emergency surgery (4%). METHOD: We reviewed 199
      patients and investigated previous disease, total white blood cells, oxygen
      saturation, albumin, body weight, type of surgery performed in regard to
      contamination, surgical time, hospitalization time, preoperative hair removal
      previous to surgery, presence of emergency surgery, and prevalence of remote site
      infections at time of surgery. All these parameters were reviewed for 48 h before
      and after the surgical procedure and every risk factor acquired a number with
      respect to the established risk in the world literature. An index called
      Prognostic index of surgical infections (PISI) was performed, made up of the
      addition of risk factors. Every patient was observed 10 days after the surgical
      procedure searching for abdominal or wound infection and correlating the index
      with the presence of surgical infection. RESULTS: Patients with a prognostic
      index of 12 or less did not show infections in any case; those with an index of
      13 to 15 points had 30% of risk infection, 16 to 18 obtained 70%, 19 to 21
      acquired 90%, and 22 or more obtained 100% of surgical risk infection.
      Sensitivity was 100% and specificity, nearby 75%. CONCLUSIONS: PISI is a reliable
      indicator of surgical infection risk because it takes into account all factors
      that cause troubles in the patients, and has high sensitivity and very good
      specificity.

PMID- 11464634
TI  - Taking account of quality. Discussion.
AB  - Another report from the Institute of Medicine in March 2001 has joined a large
      body of literature documenting serious quality and safety problems. Eight health
      care leaders discuss ways in which organizations can reduce medical errors and
      improve patient outcomes.

PMID- 11464635
TI  - Reducing health care risk. The challenge is to make everyone feel accountable.
AB  - Are employees punished or praised for acknowledging errors, raising concerns
      about safety, or identifying recurrent medical mishaps? To reduce risk, managers
      must promote a safety culture where everyone shares a sense of accountability and
      takes responsibility for high-quality care.

PMID- 11464636
TI  - Road signs, gym equipment, child care.
AB  - A growing number of health care organizations have expanded their definition of
      preventive care by supporting community programs. Education, homelessness,
      poverty, nutrition, physical fitness, drugs, and risky behaviors are some issues
      being addressed.

PMID- 11464637
TI  - The benefits of using hospitalists.
AB  - A good hospitalist program will more than pay for itself by improving outcomes,
      reducing length of stay, and enhancing hospital efficiency. Moreover, the program
      can often attract primary care physicians who prefer to use the service of a
      hospitalist.

PMID- 11464638
TI  - 20 years of health care marketing.

PMID- 11464639
TI  - Healing relationships.

PMID- 11464640
TI  - A new approach to health care delivery.

PMID- 11464641
TI  - Evidence-based consumerism.

PMID- 11464642
TI  - The butler did it.

PMID- 11464643
TI  - Countering the physician's belief system.

PMID- 11464644
TI  - [Cardiovascular disease in kidney transplantation].

PMID- 11464645
TI  - [The angiotensin gene in essential arterial hypertension].

PMID- 11464646
TI  - [Molecular genetic changes identified in tubular disorders affecting water
      electrolyte transport].

PMID- 11464647
TI  - [Survival markers in dialysis].

PMID- 11464648
TI  - [Patients with end-stage chronic renal insufficiency on programmed withdrawal
      from dialysis].
AB  - The voluntary discontinuation of dialysis by patients is a common mode of death
      in dialysis programmes. Unfortunately the Spanish experience has not been related
      in the nephrological literature. Initiation of, and withdrawal from, dialysis
      pose ethical questions for medicine in the 21st century. The dialysis population
      is aging and they have multiple medical problems. The choice may be between
      prolongation of quantity or quality of life. We evaluated a protocol for
      initiation of dialysis in patients with end stage renal failure and their
      subsequent withdrawal. We determined the factors predicting withdrawal of
      dialysis and revised the protocol to take account of these. We carried out an
      opinion poll of doctors and nurses about the effectiveness of the protocol. We
      studied prospectively the reasons for death of patients in the last seven years.
      RESULTS: Thirty patients were withdrawn from dialysis out of 116 who died during
      treatment by hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) in
      the last seven years. Vascular nephropathy is the principal disease predicting
      withdrawal from dialysis; the main precipitating cause is mental incapacity. The
      availability of a protocol for withdrawal of dialysis is well received by doctors
      and nurses and it engenders moral and legal calm when facing difficult decisions.
      Twenty-six per cent of deaths on regular dialysis are the result of withdrawal of
      treatment.

PMID- 11464649
TI  - [Risk factors associated with survival in patients in a peritoneal dialysis
      program].
AB  - The aim of this study was to quantify the effect of different mortality risk
      factors in peritoneal dialysis and to establish a prognostic index that could
      predict mortality risk when patients start dialysis. A prospective study was
      performed on 103 patients included in our peritoneal dialysis program. The mean
      follow-up time was 26 +/- 21 months. A multivariate analysis (Cox regression was
      made to identify different risk factors that could influence patient survival
      during peritoneal dialysis. Age, gender, parathyroid hormone, albumin,
      cholesterol, and the presence of diabetes mellitus were evaluated as potential
      risk factors. Patients were distributed in three groups (high, medium and low
      risk), according to the risk factors with a significant influence in multivariate
      analysis, and patient survival was studied depending on the prognostic index
      using Kaplan-Meier estimator. Overall patient survival was 90% (95%CI: 83 to 96%)
      after the first year and 40% (95%IC: 32 to 58%) after 5 years of follow-up. The
      Cox regression analysis identified albumin below 4 g/dL (RR: 2.57; 95% CI: 1.16
      to 5.72), age older than 65 years RR: 3.10; 95%IC: 1.20 to 7.98) and diabetes
      mellitus (relative risk, RR: 4.36; 95%IC: 1.43 to 13.31) as independent risk
      factors for mortality in patients receiving peritoneal dialysis. Patient survival
      after two years was 40% (95%IC: 31 to 59%), 73% (95%IC: 60 a 86%) and 100% (p <
      0.05), respectively. Malnutrition and related factors in patients receiving
      peritoneal dialysis are associated with a higher mortality rate.

PMID- 11464650
TI  - [Effect of folic acid supplementation on total homocysteine levels in
      hemodialysis patients].
AB  - Hyperhomocysteinemia is an independent risk factor for cardiovascular mortality
      in ESRD, but about 80% of total homocysteine (tHcy) is bound to albumin (alb). We
      have tried, prospectively, to reduce tHcy levels by using folic acid (f.a.) and
      vitamin B6 (P.P.) supplementation. All patients on HD, not receiving f.a. or P.P.
      and all new patients, after their third month on HD, were supplemented with f.a.
      5 mg/48 hours p.o and P.P. 40 mg/week. We determined folate, P.P. (RIA), vit.
      B12, KTV, residual renal function (KRU), PCRn, alb and tHcy levels (HPLC). 80
      patients, age 62.6 +/- 13.6 years, time on HD 16.2 +/- 25.1 months, all dialysed
      with AN69 or PPMA, and bicarbonate, were included. The prevalence of
      hyperhomocysteinemia was 84.4%, and P.P. deficit was present in 32%, with folate
      in the low normal range. At the beginning of the study, before supplementation,
      tHcy was negatively correlating only with folate (r = -0.336) (p = 0.01), and not
      with P.P., vitamin B12, age, albumin, KTV, KRU or PCRn. 58 patients received six
      months of supplementation, with normalization of P.P. levels, a significant
      increase of folate (7.25; I.C = 95% confidence intervals: 6.45, 8.05 vs 61.29;
      I.C.: 44.47, 78.11) (p < 0.001), and decrease of tHcy (24.1; IC: 21.5, 26.3 vs
      19.9; I.C: 17.5, 22.4) (p < 0.05). 33 patients have received 12 months of
      supplementation, but in spite of a continued increase of folate (100.78; I.C:
      74.81, 126.74) (p < 0.001), only 3 have normal levels of tHcy; correlating
      directly tHcy with albumin (r = 0.56) (p = 0.001), that had increased compared to
      the beginning of the study (3.39; I.C. 3.29, 3.49 vs 3.50; I.C: 3.37, 3.63) (p <
      0.05). CONCLUSION: After f.a. and P.P. supplementation, though initially tHcy is
      reduced, this response is short lived, and tHcy directly correlates with albumin
      levels. Good nutrition associated with HD adequacy, in absence of B vitamin
      deficits, seems to be the best determinant of tHcy levels rather than its removal
      by dialysis tHcy levels should be interpreted taking into account the serum
      albumin.

PMID- 11464651
TI  - [Aluminum and uremic bone disease. Diagnostic utility of serum aluminum and the
      deferoxamine (DFO) test ].
AB  - The optimal control of aluminium content in dialysis fluids has resulted in a
      decrease in the incidence of aluminium related bone disease (ARBD) and in the
      risk for aluminium toxicity. Nevertheless the problem has not disappeared. Bone
      biopsy with specific staining for Al remains the only reliable method for the
      diagnosis of ARBD. Currently there is not a total agreement on the reliability of
      serum Al levels and of the DFO test in the identification of patients with Al
      overload or toxicity. In a series of patients (mean age 48 +/- 14 years old) from
      our hemodialysis units we carried out bone biopsy and we studied the prevalence
      of bone aluminium overload and of ARBD and the usefulness of serum aluminium and
      of DFO test in their diagnosis. Seventy- three bone biopsies were evaluated by
      histomorphometric analysis and aluminium staining (Aluminon). Al overload was
      diagnosed when the Aluminon staining was positive independent of the bone surface
      covered with Al and of the bone formation rate (BFR). Patients were consider to
      have ARBD when aluminium covered > 25% of bone surface and BFR was < 0.031 micron
      3/micron 2/day. Fifteen patients had aluminium overload while 7 patients were
      considered to have ARBD. Positive Aluminon staining appeared in all
      histopathological forms of renal osteodystrophy although it appeared mainly in
      patients with mixed lesion and osteomalacia. Most of the patients with adynamic
      bone disease had negative Aluminon staining. Patients with aluminium overload
      showed lower bone formation and mineralization rates. Serum aluminium levels
      below 40 micrograms/l were useful to exclude bone aluminium overload. Serum
      aluminium levels and DFO test were not specific in diagnosing aluminium overload
      or ARBD. A DFO test with an increment in serum aluminium over 100 micrograms/l in
      combination with a serum PTH below 200 pg/ml was useful to diagnose ARBD.

PMID- 11464652
TI  - [Endoluminal percutaneous thrombectomy as a treatment for acute vascular access
      thrombosis: long-term results of 123 procedures].
AB  - Percutaneous treatment of thrombosis of occluded vascular access (VA) for
      haemodialysis (HD) has been an alternative to surgical and pharmacological
      treatments, but long term results are not well defined. The aim of our study was
      to analyse the long term results of percutaneous thrombectomy as a treatment of
      occluded VA for HD. We conducted a prospective study from june 1995 to april
      1999, including 123 consecutive thrombectomies in 64 VA in patients submitted to
      our hospital because of recent thrombosis of VA for HD. We used two different
      techniques, hydrodynamic catheter thrombectomy (Hydrolyser) in the 42 first
      procedures (34.1%), and since october 1996 we used mechanical balloon
      thrombolysis in the remaining 81 patients (65.9%). Underlying stenoses were
      evaluated by angiography, and treated by angioplasty. After the procedure,
      intravenous heparin was administered for 24 hours. The VA were 28 Brescia-Cimino
      arteriovenous fistulae (30.4%) and 64 PTFE grafts (69.6%). PATIENT
      CHARACTERISTICS: mean age: 63 +/- 15 years (18-84), previous VA: 3.3 +/- 2.5 (0
      9). The mean follow-up was 10.5 +/- 8.6 months (3-35). Percutaneous thrombectomy
      was able to remove the clots in 120 instances (technical success: 97.5%). After
      the thrombectomy 15 patients (16.3%) were immediately referred to the surgeon to
      perform a new VA due to vascular lesions in which percutaneous treatment was not
      indicated. Thirteen cases (14.1%) showed early thrombosis (< 72 hours). During
      the follow-up, 27 cases developed thrombosis (30%) and 26 VA were still patent
      (28.3%). In 23% of perfusion lung scans and in 2 of the 5 angiographies performed
      after thrombectomy, subsegmentary or segmentary perfusion defects were detected,
      without clinical significance. There were no relevant undesirable effects related
      to the technique and no symptomatic pulmonary embolism. In summary, percutaneous
      thrombectomy, whether hydrodynamic or mechanical, has shown to be an efficacious
      treatment of VA thrombosis for HD, preserving the VA with satisfactory long-term
      results.

PMID- 11464653
TI  - [Physical symptoms and emotional disorders in patient on a periodic hemodialysis
      program].
AB  - OBJECTIVES: To establish the frequency and severity of somatic symptoms and
      emotional distress (anxiety and/or depression) among our chronic hemodialysis
      (CHD) patients and to study the relationship between them as well as their
      influence on the perceived health status. PATIENTS AND METHODS: All patients who
      had been on CHD for a minimum of three months were eligible for the study. Eight
      of them were excluded: six because they were unable to answer the questionnaires
      and two because they refused to participate. The 58 remaining patients were the
      subject of our study (median age 68.5 years; median duration of HD 29.5 months).
      Diverse sociodemographic and clinical data were recorded. The patients answered
      the following questionnaires: 1) The "physical symptoms" dimension of the Kidney
      Disease Questionnaire; 2) A measure of anxiety (STAI); 3) A measure of depression
      (Beck Depression Inventory and Cognitive Depression Index); and 4) The Nottingham
      Health Profile (NHP). RESULTS: The most frequent and severe symptoms were
      tiredness, itching, thirst, bone and joint pain and sleep disturbance. The
      severity of the symptoms was positively associated with female sex, and the
      presence of clinically relevant degrees of anxiety and/or depression. A quarter
      of the patients were anxious and almost half of them suffered from depression.
      Emotional disturbances were associated with the severity of somatic symptoms and
      comorbidity. Only anxiety and depression were significantly associated with the
      global NHP score; they explained 47% of its variance. A score of 50 or more in
      the "Emotional Reactions" dimensions with the NHP detected 69% of the patients
      with anxiety and 81% of those with depression. CONCLUSIONS: Somatic symptoms are
      common among patients on CHD and they appear to be associated with emotional
      distress (anxiety and depression) that influences significantly the perceived
      health status. Measuring the perceived health status by means of generic and
      specific questionnaires, may help to establish the diagnosis of these problems.

PMID- 11464654
TI  - [Automated peritoneal dialysis: impact on residual kidney function and peritoneal
      membrane permeability].

PMID- 11464655
TI  - [Distal renal tubular acidosis with rhabdomyolysis as the presenting form in 4
      pregnant women].
AB  - We describe four pregnant patients with distal renal tubular acidosis (type I)
      (DRTA) whose initial presentation was rhabdomyolysis (RML) secondary to severe
      hypokalemia. We draw attention to the unusual presentation of DRTA during
      pregnancy, the low frequency of DRTA in adult patients and RML as initial
      manifestation. In one case the DRTA was secondary to Sjogren Syndrome and the
      etiology was unknown in the rest of the cases. We discuss the potential
      pathogenic mechanisms to explain hypokalemic RML and the various causes of DRTA
      in adult patients.

PMID- 11464656
TI  - [Ciprofloxacin-induced vasculitis with cutaneous and renal involvement].
AB  - Quinolone antibiotics are frequently used in the practice of medicine.
      Nephrotoxic side effects related to the use of quinolones are uncommon. We report
      a patient in treatment with ciprofloxacin who presented with purpuric skin
      lesions and alteration of renal function. We review these antibacterial agents
      with special attention on associated adverse reactions, and present-day
      experience with the newer quinolone antibiotics.

PMID- 11464657
TI  - [Intracytoplasmic crystals and Fanconi syndrome in a patient with IgA kappa
      myeloma].
AB  - A 45 year old man with IgA-Kappa myeloma had adult Fanconi Syndrome. Examination
      of renal biopsy revealed lesions in proximal tubules without glomerular lesions
      and without intratubular casts. By electron microscopy cytoplasmic crystalline
      inclusions were observed in renal proximal tubular epithelium. Increased plasma
      cells (28%) in bone marrow aspiration also contained crystalline inclusions. The
      treatment of myeloma produced partial remission of proliferative disease and
      Fanconi syndrome. We discuss the pathogenesis of Fanconi syndrome induced by
      light chains as well as the composition of crystalline deposits and the effects
      of treatment on Fanconi Syndrome.

PMID- 11464658
TI  - [Hemolytic-uremic syndrome after myomectomy].

PMID- 11464659
TI  - [Dialysis inclusion criteria and early mortality].

PMID- 11464660
TI  - [Utility of 99m Tc MIBI gammagraphy before parathyroidectomy in patients with
      secondary hyperparathyroidism].

PMID- 11464661
TI  - [The unusual transfer of the "Spanish model" of organ donation to the United
      Kingdom].

PMID- 11464662
TI  - [Content and absorption of calcium in diets of Northwestern Mexico: a
      bibliographic retrospective].
AB  - Calcium is an essential mineral in humans for growth and development of bones and
      teeth. In adults, bone activity is limited to maintaining bone mass and in order
      to do this, an adequate intake of calcium is necessary. The objective of this
      study was to conduct a review of the information available in the literature on
      the content and availability of calcium in the diet in Northwestern Mexico. The
      diet studies show that the amount of calcium (1164 mg/d) in the diets in
      Northwestern Mexico meets the RDA for adults 25 or older and that the principal
      sources of calcium are corn tortillas, wheat flour tortillas and beans.
      Bioavailability of calcium in diets containing these foods increases when small
      amounts of dairy products are added to the diet. This same difference in the
      availability of calcium was observed in an in vivo study conducted in young
      women. We can conclude, based on the studies mentioned, that it is necessary to
      evaluate the effect of calcium in the diets of Northwestern Mexico directly in
      the general population taking into consideration factors that may play a role in
      maintaining bone structure such as exercise, age, sex.

PMID- 11464663
TI  - [The adaptation and validation of the food security scale in a community of
      Caracas, Venezuela].
AB  - This paper describes the process of modifying and validating a hunger index
      developed in the United States by Wehler et al (1992). It is part of a research
      whose main objective is to develop and validate a simple method that measures
      both quantitative (food sufficiency) and qualitative (female self-perception)
      dimensions of household food insecurity. In a pilot study, the original
      instrument was modified from a 2 point 8 item to a 4 point 12 item scale.
      Precision measured with Alpha Chronbach's coefficient was high (0.871) suggesting
      consistency in the scale's items. The instrument was applied to a sample of 238
      poor and very poor households in a peri-urban barrio of Caracas. To determine
      overall internal validity of the scale the relationship between possible
      economic, social and behavioral determinants and food security level measured
      with the scale, was analyzed. Construct validity of the scale was established
      with factor and principal components analysis. Finally, with multiple regression
      analysis evidence is presented for overall validity of the scale. Four
      determinants: predictors of food sufficiency score, monthly income per capita,
      social class, and number of children in the household predict in the expected
      direction self-perceived food security level (R2 = 0.343). Results suggest that
      this instrument, together with an abbreviated measure of food sufficiency, based
      on strategic foods may be a valid, precise, and simple method for identifying and
      monitoring households that suffer from some degree of food insecurity in poor
      urban communities.

PMID- 11464664
TI  - [Efficacy evaluation of the molasses supplementation in normal and depleted rats
      diet].
AB  - Molasses, a sugar cane by-product, has been consumed in Brazil since colonial
      times. The efficacy of molasses added to the diet of normal and depleted
      laboratory animals on growth and hemoglobin was tested. Forty weaning males rats,
      of 21 days of age, were divided into four groups of ten animals: Control (casein
      diet with 10.14% protein); Molasses (casein diet with 10.14% protein and 12.50%
      molasses); Depleted Control and Depleted Molasses, the later two submitted to
      protein depletion for the first 7 days of the trial. Animals were weighed at
      weaning (initial weight) and at the end of the experiment (final weight) and were
      fed the experimental rations and water ad libitum for 28 days (normal animals)
      and 21 days (depleted animals). Consumption was registered in order to calculate
      the Food Efficiency Ratio. At the end, animals fasted for 10 hours, killed and
      blood was collected by cardiac puncture to determine hemoglobin levels. Weight
      gain in all groups did not show statistically significant differences. Molasses
      fed animals presented a small, but not significant increase in hemoglobin levels,
      compared to the control groups. Considering the possible deleterious effects of a
      high sugar diet, that can originate furfural during food processing, it is
      necessary to conduct more studies to evaluate the utilization of these products
      for human consumption.

PMID- 11464665
TI  - [Rice and bean diets increase hepatic and plasmatic activity of
      gammaglutamyltranspeptidase in young rats].
AB  - The effect of feeding rice and bean diets in both hepatic and plasmatic activity
      of gamma-glutamyltranspeptidase-(GGT-EC 2.3.2.2) activity was evaluated in
      growing-rats (Experiment A) and mature rats (Experiment B). During 28 days, the
      animals were fed with isocaloric-diets composed by tree levels of rice, bean or
      rice-and-bean protein. Similarly with the aproteic group, a significant increase
      on both the hepatic and plasmatic GGT activity were showed with the lowest levels
      of protein, when compared with 25% casein control group. This rise was more
      effective in growing-rats fed on legume-based diets (as bean or rice-and-bean
      diets), making evident a differential effect of age and an exacerbated effect of
      the protein restriction with the lowest sulfur amino acids disposal. These
      alterations suggest a metabolic adaptation of GGT to both the inadequate protein
      and sulfur-amino acid levels, thus supporting the hypothesis that the Glutathione
      levels may be reduced by these legume-based diets.

PMID- 11464666
TI  - [Evaluation of commercial UHT milk and optimization of industrial process].
AB  - From the nutrition al point of view milk is one of the most complete food in the
      diet of mammals. It contains nearly all the nutrients necessary to sustain life,
      but milk can deteriorate very easily, either by microbiological contamination or
      by biochemical reactions during processing and/or storage. The objective of this
      research study was to design a modified UHT treatment to achieve commercial
      sterilization and maximize the stabilization of the heat-treated product during
      storage. To search for a modified UHT process, a mathematical model coupled with
      an optimization routine (complex method) was developed. The mathematical model
      considers Kinetics for the inactivation of Bacillus stearothermophilus and
      several quality factors. To attain the objective function, several commercial UHT
      milk were analyzed and for the computer search the minimization of hydroxy methyl
      furfural (HMF) formation was considered and also including constraints for
      protease and lipase inactivation. The complex optimization procedure was
      implemented to search for the optimum modified UHT treatment.. One of the optimum
      modified UHT treatments was the combination of two pre-treatment (3.16 minutes at
      62.30 degrees C and 6 minutes at 75 degrees C) in addition with a UHT treatment
      (0.75 s at 148.8 degrees C). This treatment attains the maximum product stability
      with a negligible effect on composition and color formation in the treated milk
      (HMF formation less than 3 mg/mL).

PMID- 11464667
TI  - [Technology for the whole utilization of brewer's yeast in food industry].
AB  - A flexible scheme for the fractionation of brewer's yeast was developed. The
      procedure allows the production of different products such as: dry yeast flakes,
      dry yeast pills, yeast-extract based table sauce, yeast protein concentrates and
      soy-like sauce. The investment required for the processing of one ton per day is
      below 2 million dollars with an overall profitability higher than 53%. Investment
      is recovered in 0.75 years. The production of food ingredients from yeast
      upgrades its biomass about 25 fold. Present procedure is compared with other
      biomass fractionation processes taking into account the utilization of all
      technological streams where the process becomes environmentally friendly since
      effluent production significantly lower than similar technologies.

PMID- 11464668
TI  - [Application of dielectric cooking in the elaboration of instant maize flour for
      the preparation of corn and tortilla chips].
AB  - This present work reports on the evaluation of a method for producing of instant
      flour for corn and tortilla chips based on dielectric cooking (DC). The samples
      prepared with lime showed a smaller variation in color than those without lime. A
      greater water absorption capacity was found in the samples processed without
      lime. The values for cohesion and adhesion of the DC masa prepared with lime are
      within the range of values previously reported for samples of masa prepared with
      nixtamal and commercial instant maize flours. The color analyses of chips from DC
      masa showed slight changes in relation to the chips prepared by the traditional
      process of nixtamalization. The DC tortilla chips (plus lime) with 15 minutes of
      DC showed similar values of delta E as compared to the control (commercial
      tortilla chips). The moisture of the DC chips varied in the range from 1.5 to
      2.8. The DC tortilla chips with lime absorbed a lower amount of oil than the
      control sample and the corn chips. In fact, the DC chips absorbed lower amount of
      oil as compared to the control. The DC tortilla chips with lime and processed for
      10 and 15 minutes were crunchy and smooth. Dielectric cooking displays a high
      potential for corn and tortilla chips with good functional characteristics,
      giving substantial savings of water, processing time and with higher yields due
      to the use of the whole grain.

PMID- 11464669
TI  - Nutritional value of mung bean (Vigna radiata) as effected by cooking and
      supplementation.
AB  - The study was conducted to improve the nutritional value of Mung (Vigna radiata)
      by supplementation with different kinds of meat. Diets were prepared using raw
      and cooked Mung and then cooked Mung was supplemented with poultry, mutton and
      beef at 10, 15, and 20 percent levels. Nutritional value of Mung was determined
      by chemical analysis as well as by rat assay. Mung had 25 percent protein and
      minor losses were observed during cooking. It had 1.21 percent lysine which was
      reduced by 43 percent on cooking. Other amino acids also showed losses during
      cooking. The Protein Efficiency Ratio (PER) of diet containing Mung was
      significantly reduced on cooking (1.86 vs 1.40). On the contrary cooking resulted
      in some improvement of Net Protein utilization (NPU) and True Digestibility (TD)
      of the Mung based diets. Twenty percent level of different meats showed better
      results in terms of PER, NPU and TD.

PMID- 11464670
TI  - [Biochemistry and functional characterization of squid mantle meat (Dosidicus
      gigas)].
AB  - A study for the characterization of frozen giant squid mantle (meat) protein
      stored at -25 degrees C for 8 month was started. In the present research, the
      following functional properties were investigate: emulsifying, water holding and
      gel forming capacities. Optimal conditions for the separation and differentiation
      of miofibrillar and sarcoplasmatic proteins were also studied. It was found that
      the unfrozen giant squid mantle meat es capable of emulifying 2.817,4 g of oil/g
      of protein and holding capacity was 3.64 g of water/g of protein. Related to the
      gel forming capacity, it was not obtain, probably due to excessive storage of the
      meat. With regard to miofibrilar protein obtention of the squid mantle meat, it
      was found that two low ionic strength washings (I = 0.05), the sarcoplasmic
      proteins were practically eliminated from the protein matrix. The differentiation
      of miofibrilar and sarcoplasmatic proteins was obtained by PAGE-SDS of the squid
      mantle meat extracted at two different ionic strength (I = 0.05 and I = 0.5).
      This work demonstrates that the giant squid mantle protein has a high emulsifying
      and water holding capacity, and it can be used, as a raw material, for the
      improvement of sausage products. About the gelling products, more studies will be
      necessary with fresh squid mantle meat to conclude about this functional
      property.

PMID- 11464671
TI  - [Preparation of cookies with a flour mixture of wheat and green plantain].
AB  - With the purpose of diversifying the use of green plantain flour, a functional
      evaluation was performed by substituting 7% of chocolate cookie wheat flour by
      dehydrated green plantain flour; thus allowing to obtain a product with good
      physical and organoleptic qualities, as well as a better nutritional quality, as
      for dietary fibre and resistant starch. As a result of the use of this dehydrated
      green plantain flour (G-HT/HPV), the values of some chemical components increased
      significantly (P 0.05 Pound) in comparison to the standard cookies (GP): ash
      (2.46 to 2.69%), proteins (8.93 to 9.69%), dietary fiber (4.97 to 5.40%),
      resistant starch (0.19 to 0.23%) and total sugar (25.26 to 30.55). The G-HT/HPV
      complies with the industrial requirements as for moisture (2.7300%), ph (8.43),
      aw (0.205) and color (L = 31.78; a = 7.95 and b = 10.51). Besides, thanks to the
      use of G-HT/HPV the flours scattering during the kneaded process was diminished,
      thus reducing the cookie diameter and increasing the resistance to breaking (1.48
      to 2.06 Kgf), in comparison to the GP. While evaluating the shelf life for G
      HT/HPV, it was demonstrated that was affected by moisture, pH, aw and acidity
      after the first month of storage. In the preference comparison test between the G
      HT/HPV and a trademark cookie (GC), no significant differences were founded. Both
      were accepted and qualified between good and very good, as for sensorial features
      like colour, fragrance and taste. However, significant differences were detected
      in relation to texture, and they were corroborated in the texture profile
      analysis. In this test the panel staff, while evaluating both types of cookies
      demonstrated that there are 8 features that can be used to describe them: firm,
      crumble, crisp, mealy, soft, lumpy, particle size and chewy.

PMID- 11464672
TI  - [Suitability of wild underexploited vegetables from the Argentine Chaco as a food
      resource].
AB  - The nutritional value of wild underexploited vegetable samples collected in the
      Argentine Chaco was investigated. Leaves from Hipochaeris sp.-, Coronopus didimus
      and Portulaca olearacea; fruits from Zyziphus sativa, Brumelia obtusifolia and
      Eugenia uniflora; and roots of Canna coccinea were included in this work; several
      separate samples being taken at least during two consecutive harvesting seasons.
      Values for moisture, protein, total lipids, crude fiber, ash, reducing and total
      sugars, starch, total pectins and energy are given. Mineral micronutrient
      contents are reported for calcium, potassium, magnesium, iron and phosphorus, as
      well as vitamin values (ascorbic acid and beta-carotene). Higher concentrations
      of macronutrients were found in the leafy vegetables (32-50 Kcal/100 g) than in
      commercially exploited cultivars (14-30 Kcal/100 g), as shown by an increased
      energy value, the protein content of Portulaca olearacea (3.74 g/100 g) being
      highly remarkable. Unusually high micronutrient figures were also determined in
      Coronopus didimus, with 172.3; 3.98, and 46.7 mg/100 g, for calcium, iron and
      magnesium, respectively. In general, fruits also showed higher macronutrient
      contents, with the exception of proteins, with less but constant values (1.58 to
      1.74 g/100 g), although contributing more energy than commercial cultivars (70 to
      147 Kcal/100 g). Equally important proved to be the provitamin A content in
      Eugenia uniflora (11.98 mg/100 g). Roots of Canna coccinea revealed the lowest
      energy value (34 Kcal/100 g) but surprisingly, the highest content of phosphorus
      of all the species under study.

PMID- 11464673
TI  - [Chemical composition of Creole cattle meat].
AB  - Proximal composition was determined in meat's Creole cattle (CGBC). For this
      purpose, four raw cuts of CGBC were analyzed: buttock, flank, loin blade steak,
      and shoulder blade steak. The mentioned names of the meat cuts come from the
      National Meat Bureau from the Republic of Argentina. These cuts were taken from
      an experimental lot of Creole cattle (n = 11) in Jujuy province. Comparisons were
      made with data extracted from Argentine Table of Food Composition, edited by
      National Nutrition Institute, Buenos Aires, Argentina (1942). The results show
      that the level of protein is slightly inferior (in the case of CGBC varies
      between 18.44 +/- 0.30 and 21.06 +/- 0.11 g/100 g, while in the CTE varies
      between 20 and 23.8 g/100 g). The content of lipids in the cuts without visible
      fat is variable (1.06 +/- 0.01 to 2.74 +/- 0.61 g/100 g in the cuts of CGBC and
      1.4 to 8.4 for the cuts of CTE). The content of minerals is similar (Fe 2.26 +/-
      0.18 to 2.35 +/- 0.23 mg/100 g in CGBC, while in the CTE varies between 3.15 and
      3.46 mg/100 g; Phosphorous varies between 142 +/- 10 and 170 +/- 11 mg/100 g in
      CGBC and 186 to 213 mg/100 g in CTE). These outcomes allow to affirm that the
      quality of CGBC beef is very similar to CTE beef with regard to principal
      nutrients.

PMID- 11464674
TI  - Nutritional composition and vitamin C stability in stored camu-camu (Myrciaria
      dubia) pulp.
AB  - Camu-camu (Myrciaria dubia), a native fruit of the Amazon region, is one of the
      richest sources of vitamin C (2.4 to 3.0 g/100 g in the pulp) found in Brazil.
      The purpose of this work was the physical-chemical characterization of some
      nutrients and the valuation of vitamin C stability in stored camu-camu pulp,
      produced by the Agronomic Institute of Parana (IAPAR), Parana State, Brazil. The
      vitamin C determination was made by titration with potassium iodate. The fruit
      produced in Parana State, presented a lower content of vitamin C than the one
      native of the amazon region, possibly due to the different development conditions
      of the plant, and consequently of the fruit, as well as the climatic variation,
      the humidity and the characteristics of the soil. Regarding the vitamin C
      stability in stored (-18 degrees C) camu-camu pulp, a considerable decrease in
      its concentration until the 28th day was observed lost 23% (from 1.57 to 1.21
      g/100 g), staying approximately the same until the end of the experiment. After
      335 days of storage, the content found was of approximately 1.16 g/100 g of pulp,
      the ascorbic acid losses amounted to 26%. This content was still higher than the
      one found for most fruits that are good sources of this vitamin.

PMID- 11464675
TI  - [Comparative proximal and mineral analysis of iguana,poultry and beef meats].
AB  - Raw meat samples from iguana, poultry and beef cattle specimens were used to
      compare proximal (g/100 g) and mineral (mg/100 g) composition. Iguana meat was
      obtained by dissecting whole specimens (Iguana iguana) captured at a ranch (n =
      20). Thighs and breasts were separated from broiler (either chilled or frozen)
      carcasses (n = 20), and deboned to represent chicken meat samples, whereas 2.5-cm
      thick longissimus (ribeyes) steaks were removed from carcasses and frozen to
      represent beef of several breed types (n = 20). The one-way analysis of variance
      performed by the least squares method (LS Means) showed specie affected
      significantly (p > 0.05) all composition variables under study. Moisture content
      did not differ between iguana and chicken meats (74.7 y 74.9%, respectively)
      whereas beef samples had the lowest water content (73%) (p < 0.01). LS means for
      protein content showed beef samples (22.3%) were highest (p < 0.05) in this
      nutrient, iguana meat being intermediate (20.8%). Chicken meat presented the
      highest amount of total lipids (7.75 +/- 0.20 g/100 g) (p < 0.01) followed by
      iguana (3.49 +/- 0.12 g/100 g) and beef (2.57 +/- 0.20 g/100 g). Ash and most
      individual minerals were more concentrated in iguana meat, except for K and Zn
      that were more abundant in beef samples. Non-significant differences in Mg, Na,
      Cu or Mn contents were detected between chicken and beef samples. It was
      concluded that iguana meat could be an alternate source of protein and minerals
      as compared to those of traditional meat species.

PMID- 11464676
TI  - [Finally a better financing for home hemodialysis].

PMID- 11464677
TI  - [Can medical research contribute to global equalization?].

PMID- 11464678
TI  - [High blood pressure].

PMID- 11464679
TI  - [Emergency dialysis at Haukeland hospital in 1999].
AB  - BACKGROUND: The incidence of acute renal failure requiring dialysis is not known
      in our country. The criteria for acute dialysis are not uniformly accepted,
      neither is there consensus on dialysis strategy in critically ill patients. We
      describe the acute dialysis activity in our hospital in 1999. MATERIAL AND
      METHODS: We have retrospectively recorded the indications for dialysis and the
      course and hospital mortality in all patients treated with acute dialysis in
      1999. RESULTS: 108 patients were treated with 670 dialysis procedures; the
      incidence was 20.5 per 100,000 inhabitants. Continuous veno-venous
      haemodiafiltration accounted for 37% of all treatments. In 50% of the patients
      acute renal failure occurred after surgery or serious infections with a mortality
      of 57% and 62% respectively. Total dialysis mortality was 45%. The mortality in
      patients with malignancy and peripheral vascular disease was 90% and 75%
      respectively. 10% of the patients needed chronic dialysis. INTERPRETATION: The
      incidence of acute dialysis was higher than previously reported from European
      countries and may be related to the general increase in active treatment of
      patients with complicated diseases. The mortality rates are persistently high.
      Close cooperation between nephrologists and intensivists in the treatment of
      these patients is essential.

PMID- 11464680
TI  - [Acute renal failure caused by hypercalcemia].
AB  - BACKGROUND: Hypercalcaemia may cause acute renal failure. MATERIAL AND METHODS:
      We present and discuss two patients with acute renal failure caused by
      hypercalcaemia. RESULTS: Patient no. 1 was treated with too high doses of vitamin
      D for hypoparathyroidism. Patient no. 2 had been taking extremely high doses of
      calcium carbonate for dyspeptic pain. Volume depletion and renal vasoconstriction
      are the mechanisms that lead to acute renal failure. Long-lasting hypercalcaemia
      will lead to calcium deposits in the kidneys (nephrocalcinosis), which is known
      to cause chronic renal failure. INTERPRETATION: It is mandatory to start early
      treatment for serious hypercalcaemia. If treatment is started in time, the renal
      failure may be reversible. Constant vigilance is essential when patients are
      treated with vitamin D.

PMID- 11464681
TI  - [Acute renal failure, renal artery stenosis and angiotensin-converting enzyme
      (ACE) inhibitor].
AB  - BACKGROUND: Acute renal failure is a well-known complication in patients with
      renal artery stenosis during treatment with ACE inhibitor. Renal artery
      thrombosis after withdrawal of ACE inhibitor has not been reported previously.
      MATERIAL AND METHODS: We describe a patient with acute renal failure with an
      unexpected course. RESULTS: A 67-year-old man was admitted with acute anuric
      renal failure during treatment with hydrochlorothiazide and enalapril. His blood
      pressure was 165/60 mm Hg. Renal ultrasound was normal. After initial rehydration
      and dialysis, diuresis resumed until a sudden unexpected anuric renal failure
      recurred on day 12. Angiography disclosed bilateral renal artery occlusion. The
      right renal artery was successfully opened and a stenosis was blocked and
      stented, and brisk diuresis ensued. Two days later hypertension accelerated, and
      a new invasive procedure on day 24 succeeded in opening, blocking and stenting a
      proximal stenosis in the left artery; a mobile thrombus was located behind the
      stenosis and successfully treated with intraarterial thrombolysis. Blood pressure
      rapidly normalized, and serum creatinine was normal on visits 1.5 and 4 months
      later. INTERPRETATION: General aspects and prevention of acute renal failure
      during ACE inhibitor therapy are discussed. Acute renal thrombosis after
      withdrawal of ACE inhibitor in patients with stimulated renin angiotensin system
      and significant renal artery stenosis may be causally related to the
      antifibrinolytic effects of angiotensin II and aldosterone. Endovascular
      reconstruction of renal artery occlusion may completely restore the kidney
      function.

PMID- 11464682
TI  - [Bilateral renal artery stenosis--a cause of acute pulmonary edema].
AB  - BACKGROUND: Renal artery stenosis may present as acute pulmonary oedema and be
      misinterpreted as congestive heart failure. ACE inhibitors and angiotensin-II
      antagonists are widely used among patients with congestive heart failure and
      hypertension. MATERIAL AND METHODS: The authors present a patient with congestive
      heart failure caused by a combination of coronary heart disease and bilateral
      renal artery stenosis. The patient developed acute kidney failure secondary to
      ACE inhibitor and angiotensin II antagonist treatment. RESULTS: Mechanisms behind
      pulmonary oedema secondary to renovascular hypertension are discussed.
      INTERPRETATION: Revascularisation is the treatment of choice for this patient
      category.

PMID- 11464683
TI  - [Quality of rapid tests for determination of infectious mononucleosis].
AB  - BACKGROUND: The Norwegian centre for quality assurance in primary health care,
      NOKLUS, was established in 1992 to ensure the quality of laboratory analyses
      performed in primary health care. This article evaluates results from the surveys
      of infectious mononucleosis. MATERIAL AND METHODS: From 1996 to 2000, five serum
      panels were sent to participating practices in order to control test-kits
      designed for serological rapid diagnosis of infectious mononucleosis. 648
      practices participated in this external quality assessment in 2000. Target values
      were determined using the Paul Bunell Davidsohn test. The results obtained for
      each type of test and variables that might have affected the results were
      evaluated. RESULTS: Outdated kits or kits close to the date of expiration showed
      poorer results than the other test-kits. The quality of the results depended
      mainly on the type of test-kit used and the training level of the persons
      performing the analyses. INTERPRETATION: The best performing tests in these
      surveys were Clearview IM (Unipath Limited) and Contrast Mono (Genzyme
      diagnostics). These two tests are among the three most frequently used tests, out
      of a total of thirteen, in our surveys.

PMID- 11464684
TI  - [Encephalitis after acute Epstein-Barr virus infection].
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection is known to cause severe
      neurological complications such as encephalitis. MATERIAL AND METHODS: We present
      the history of two men, aged 17 and 22, who developed encephalitis after acute
      primary EBV infection. One of them survived with cerebral complications, the
      other died. RESULTS: One of them had the classic presentation of infectious
      mononucleosis and EBV-specific findings in the cerebrospinal fluid. The other had
      neither signs of infectious mononucleosis nor specific findings in the
      cerebrospinal fluid such as EBV-PCR. Nevertheless, the clinical features of
      encephalitis were very similar. They were characterized by memory problems,
      personality changes, reduced consciousness, brainstem disorders and epileptic
      seizures. CT and MRI findings indicated involvement of basal ganglia and limbic
      structures. None of them responded to acyclovir. INTERPRETATION: We conclude that
      EBV infection can lead to severe cerebral complications without general symptoms
      of infectious mononucleosis and specific serologic findings in the cerebrospinal
      fluid.

PMID- 11464685
TI  - [Two cases of pneumococcal pericarditis].
AB  - BACKGROUND: Bacterial pericarditis is often overlooked, partly because symptoms
      and signs associated with pericarditis are frequently missing, but also because
      of the rarity of the disease. MATERIAL AND METHODS: Two cases of pneumococcal
      pericarditis treated at Ullevaal University Hospital are presented. RESULTS:
      Pneumococcal pericarditis is a rare, but serious complication to infections like
      pneumonia, pleural empyema, and septicaemia. Patients with an infectious disease
      who develop signs of elevated central venous pressure, enlarged cardiac
      silhouette on chest x-ray, or severe hypotension should have an echocardiography
      performed. If pericardial fluid is present, a diagnostic pericardiocentesis
      should be considered. INTERPRETATION: Treatment consists of drainage and
      antibiotics. Pericardiocentesis and subxiphoid catheter drains may be inadequate
      because of fibrin precipitation resulting in organization of the fluid. In these
      cases surgical intervention has traditionally been recommended, but
      intrapericardial fibrinolysis could be an alternative.

PMID- 11464686
TI  - [24-hour blood pressure monitoring and albumin excretion in urine in
      hypertension].
AB  - BACKGROUND AND OBJECTIVES: Microalbuminuria, a subclinical increase of albumin
      excretion in urine, is a novel recognized risk factor for atherosclerosis in
      essential hypertension. This study aimed to look at the association between
      ambulatory blood pressure and urinary albumin excretion (UAE) in hypertensive
      subjects. MATERIAL AND METHODS: 140 patients aged 50.1 +/- 11.6 years, referred
      for 24-hour ambulatory blood pressure monitoring (ABPM), were studied. A separate
      analysis was performed in 46 persons with newly diagnosed and untreated essential
      hypertension. Albumin excretion was evaluated by determining the
      albumin/creatinine ratio (ACR) in the first voided morning urine sample.
      According to the ACR, patients were categorized as having normoalbuminuria (ACR <
      1.5 mg/mmol), borderline microalbuminuria (1.5 < or = ACR < 3.0 mg/mmol) and
      overt microalbuminuria (ACR > or = 3.0 mg/mmol). RESULTS: ACR was significantly
      higher in hypertensive than in normotensive individuals (2.17 +/- 2.67 and 1.72
      +/- 2.97 mg/mmol respectively, p = 0.012). Average 24-hour, daytime and nighttime
      systolic as well as diastolic blood pressures were lower in patients with
      normoalbuminuria than in the other two groups and did not differ among the two
      microalbuminuric groups. A close relationship between ACR and ambulatory BP was
      observed, even for the subgroup of newly diagnosed and untreated hypertensive
      patients. INTERPRETATION: A close relationship is observed between ambulatory
      blood pressures and albumin excretion rates in the microalbuminuric and
      normoalbuminuric range. Further studies are needed to assess the threshold level
      of ACR when screening for microalbuminuria in hypertensive patients.

PMID- 11464687
TI  - [Ambulatory and home blood pressure monitoring].
AB  - BACKGROUND: Ambulatory blood pressure measurements may be performed with manual
      or automatic devices. Such methods seem to be increasingly used for diagnosing
      conditions like "white coat hypertension" or abnormal variations in the 24-hour
      blood pressure profile. However, it is not yet known whether these patients are
      exposed to an increased risk of cardiovascular events. MATERIALS AND METHODS:
      This paper is a summary of systematic reviews (health technology assessment
      reports) of the performance and effectiveness of ambulatory blood pressure
      measurements for the diagnosis of hypertension. RESULTS: Ambulatory blood
      pressure measurements may be used during medical treatment for hypertension to
      control blood pressure, and patients using these measurements have been shown to
      reach the target blood pressure at lower medication levels than patients
      depending on blood pressure measurements in the surgery. INTERPRETATION:
      Widespread use of ambulatory blood pressure measurements in order to predict
      cardiovascular risk requires knowledge about diagnostic and prognostic
      performance. There are studies that address these concerns, but major weaknesses
      in study design limit their value. The lack of a consensus on reference values is
      also an impediment to the use of ambulatory blood pressure measurements.

PMID- 11464688
TI  - [Acute infectious myelitis].
AB  - BACKGROUND: Acute myelitis is a clinical condition affecting the motor, sensor or
      autonomic function of the spinal cord. The etiology is often unknown, although a
      diversity of pathogens have been associated with acute myelitis. MATERIALS AND
      METHODS: Based on relevant literature we present an overview of the most
      important pathogens responsible for infectious acute myelitis in northern Europe,
      as well as recommendations regarding diagnostic guidelines. RESULTS: The
      pathogenic mechanisms are only partly known. Both replication of the pathogen,
      cellular defence mechanisms after invasion of the central nervous system, and the
      immune system seem to be important for the neurological damage. INTERPRETATION:
      Identification of a causative agent is important for the etiologic diagnosis and
      offers the possibility of specific treatment.

PMID- 11464689
TI  - [Significant decline in blood pressure levels after 1996--fact or artefact?].
AB  - BACKGROUND: Since 1985, the National Health Screening Service has regularly
      offered men and women aged 40-42 years in all Norwegian counties except Oslo a
      cardiovascular disease risk factor screening. After 1996, a substantial decline
      in blood pressure levels was observed. MATERIAL AND METHODS: Data from eight
      counties which were screened both in 1994-96 and 1997-99. RESULTS: Mean
      systolic/diastolic blood pressure was 135.3/81.1 and 129.2/75.7 mm Hg in men and
      126.1/75.9 and 119.4/70.3 mm Hg in women. The change in blood pressure is
      considered in relation to methodological aspects, such as blood pressure devices,
      situation, whether the measurements have been taken in ambulatory buses or
      indoors, and also in relation to life-style and other factors linked to blood
      pressure. CONCLUSION: No reasonable explanation for the blood pressure decline
      has been traced.

PMID- 11464690
TI  - [Ischemic stroke in children--a diagnostic challenge].
AB  - BACKGROUND, MATERIAL AND METHODS: Ischaemic cerebral infarctions are relatively
      uncommon in childhood, and the aetiologies seen in this age group are different
      from those commonly seen in adults. This study presents clinical findings,
      investigation results and outcome in a five-year material collected between 1994
      and 1999 in our department. It includes 22 children with ischaemic strokes aged
      three months to 13 year at the first or only stroke episode. RESULTS: The
      symptoms caused by ischaemic strokes in this age group vary and are often
      combined. Motor symptoms dominate, and we found hemiplegia, facial palsy, visual
      disturbances and reduced consciousness, listed according to decreasing
      occurrence. Infections and cardiac diseases or procedures were the most common
      aetiologies, both occurring with 22%. Other groups were autoimmune diseases
      (14%), malignancies (5%) and dissection of the a. carotis after trauma (5%). None
      of the patients in this material died as a result of the ischaemic stroke; 27%
      recovered completely. 41% had light sequela, 18% moderate sequela, and 14% ended
      up severely disabled. 18% had recurrent stroke episodes. INTERPRETATION:
      Appropriate examination after stroke in childhood is of great importance, since
      some of the aetiologies are associated with recurrence risk. Based on our
      clinical experiences and literature studies, we suggest a plan for diagnostic
      evaluation and treatment strategies for children who undergo an acute cerebral
      vascular disease.

PMID- 11464691
TI  - [Metformin and contrast media--increased risk of lactic acidosis?].
AB  - A rare side effect from metformin is lactic acidosis. There have been much
      concern about the reported risk when metformin was combined with contrast medium.
      Almost all reported cases following combination with contrast media occurred when
      pre-existing poor renal function was present. A recent review of the literature
      has resulted in new recommendations in Europe and the USA. We suggest new
      guidelines for Norway with regard to the use of metformin in patients undergoing
      radiological examination with contrast media.

PMID- 11464692
TI  - [Erik Gerhard Schytte--Dioceseos Nordlandiae Aesculapius--city medical officer].
AB  - Erik Gerhard Schytte (1728-1808) was born in Vega in Northern Norway. He read
      theology at the University of Copenhagen, but like other Norwegian theological
      students at the time, he also took an interest in medicine and attended lectures
      in the field. During some periods, Schytte substituted for the city medical
      officer in Bergen. In 1754 he graduated in theology in Copenhagen and went on to
      become a vicar in various parishes in Northern Norway, working partly as a vicar
      and partly as a medical practitioner and turning his vicarage into a kind of
      hospital. He was the first person with a medical education who practiced medicine
      in Northern Norway. For his contribution to the medical services in that region,
      he was appointed honorary professor by the government in Copenhagen. Schytte was
      widely known as the Aesculap of Northern Norway.

PMID- 11464693
TI  - [How are my receptors, doctor?].

PMID- 11464694
TI  - [A new special tuberculin is expected to improve diagnosis of tuberculosis].

PMID- 11464695
TI  - [More home hemodialysis!].

PMID- 11464696
TI  - [Scientific basis of the blood group diet].

PMID- 11464697
TI  - [Best when it comes to health services, health status and life style?].

PMID- 11464698
TI  - [Methicillin resistant Staphylococcus aureus in Oslo in 2000].

PMID- 11464699
TI  - [Acupuncture in acute lumbago].

PMID- 11464700
TI  - [Air ambulance service should be managed according to the premises of health
      care].

PMID- 11464701
TI  - [State air ambulances and "physicians of the air"].

PMID- 11464702
TI  - [How to find Nordic articles on the Internet?].

PMID- 11464703
TI  - [The obligation to refer--one more time].

PMID- 11464704
TI  - [Why research courses for medical students?].

PMID- 11464705
TI  - [The role of metalloprotease in pathogenesis of nervous system diseases].
AB  - Matrix Metalloproteases (MMPs) comprise a big family of proteolytic enzymes
      secreted into extracellular matrix and involved in remodelling of many tissues.
      The MMPs' activity is regulated on many levels. It is also determined by specific
      inhibitors known as tissue inhibitors of metalloproteases (TIMPs). Several
      studies revealed that MMPs have a role not only in physiological processes but
      also in pathophysiology of nervous system diseases, such as multiplex sclerosis,
      Guillan-Barre syndrome and strokes. Concerning demyelination MMPs are responsible
      for degradation of myelin components and facilitation of immune cells migration
      into inflammatory sites by degrading vascular basement membrane. We still
      investigate substances with positive clinical effect on the nervous system
      diseases due to MMPs inactivation.

PMID- 11464706
TI  - [Conduction disturbances and cardiac arrhythmias in myotonic dystrophy--diagnosis
      and clinical significance in adult populations].
AB  - Myotonic dystrophy (DM) is the most frequent adult form of muscular dystrophy.
      The clinical presentation consists of both muscular and systemic involvement. One
      of the main causes of high mortality is sudden cardiac death due to
      tachyarrhythmias and conduction disturbances. The knowledge of cardiovascular
      complications is very important because of diagnostic and therapeutic
      possibilities. The main cardiological complications of DM are arrhythmias
      associated with the destruction of the conduction system. The main
      electrocardiographic changes (prolongation of the P-R interval, left anterior
      hemiblock, increased QRS duration) reflect destruction of the His-Purkinje system
      and may progress very rapidly, leading to death due to Stokes-Adams attacks. The
      most frequent tachyarrhythmias are atrial and ventricular extrasystoles, atrial
      flutter and fibrillation, as well as ventricular tachycardia, that can be a cause
      of sudden death. The mechanisms underlying ventricular arrhythmias are conduction
      disturbances, prolongation of the QT interval, impaired coronary reserve and
      autonomic function. A common type of tachycardia seen in patients with DM is that
      originating from the branches of the bundle of His (bundle-branch re-entry). Risk
      stratification (in respect of cardiological complications) is possible on the
      basis of electrophysiological studies, clinical symptoms and a family history.
      Invasive electrophysiological investigation and implantation of a pacemaker may
      be indicated in patients with electrocardiographic features of a significant
      disease of the conduction system. Multicentre clinical trials assessing the
      efficacy of this therapeutic strategy are underway.

PMID- 11464707
TI  - [Direct fixation of odontoid process base fractures].
AB  - Fractures of the base of odontoid process are serious spinal injuries. Their
      treatment still remains controversial. External rigid immobilisation is the way
      of conservative healing. Operations by posterior approach: posterior atlantoaxial
      fixation, atlantoaxial transarticular screw fixation or even occipitocervical
      fixation limit range of head motion. Direct odontoid screw fixation preserves
      normal motion of C1-C2 junction. Success of this method depends on proper
      patients selection. The authors present description of surgical technique based
      on literature review and their own experience. The authors perform odontoid
      fixation by means of single cannulated cancellous screw guided by K-wire. This
      wire provides stability of broken odontoid process during procedure of screw
      insertion. Old fracture--1 case in author's experience--has been curetted before
      fixation. The authors reviewed clinical efficacity and results of direct odontoid
      screw fixation published in current literature.

PMID- 11464708
TI  - [Encephalopathy and other neurologic syndromes with familial occurrence].
AB  - A review is presented of literature data concerning vascular disease occurring in
      families. They manifested clinically as recurrent TIA, ischaemic and haemorrhagic
      strokes and other blood supply disturbances and lead to numerous vasogenic brain
      tissue damage of various intensity. Particularly evident lesions are observed in
      hemispheric white matter. Progressive neurological symptoms and dementia form the
      picture of subcortical leucoencephalopathy in several members of a family.
      Moyamoya disease, fibromuscular dysplasia, hereditary haemorrhagic
      telangiectasia, hereditary cerebral haemorrhage with amyloidosis, pseudoxanthoma
      elasticum, two types of subcortical encephalopathy in Japan, HERNS and CADASIL
      are described.

PMID- 11464709
TI  - [Syringomyelia associated with intracranial tumors. Case report and literature
      review].
AB  - A case of 39 years old woman with two intracranial meningiomas and syringomyelia
      is presented. Large right-sided tentorial meningioma in cerebellopontine angle
      and middle cranial fossa and small left sided sphenoid wing meningioma co-existed
      with secondary tonsillar herniation and large syringomyelic cavity in cervical
      and thoracic spinal cord. The patient had dissociated sensory loss on trunk and
      upper left extremity, muscle atrophy, left hand paresis, long tracts signs. After
      having done atlanto-occipital decompression, the intramedullary cavity collapsed
      and neurological symptoms resolved. Two months later large tentorial meningioma
      was successfully removed via occipito-suboccipital craniotomy with tentorial
      transsection. A review of the literature concerning syringomyelia secondary to
      intracranial tumours was done. To our knowledge this is the first such case
      described in which syringomyelia syndrome was the prominent symptom of the
      disease and two staged surgical procedure, first oriented at treatment of
      syringomyelia itself, was applied.

PMID- 11464710
TI  - [SUNCT syndrome--case report].
AB  - Short-lasting unilateral neuralgiform headache attacks with conjunctival
      injection and tears (SUNCT) syndrome is a very rare disorder, first described by
      Sjaastad et al. in 1989. The authors report a case of that type of headache in an
      80 years old woman. They also discuss the pathophysiology and treatment.

PMID- 11464711
TI  - [Percutaneous vertebral surgery. Indications, technics and possibilities].
AB  - The authors report their own experience with percutaneous vertebroplasty, one of
      the so called--minimally invasive methods, used to treat a certain group of
      spinal lesions affecting the vertebral bodies. The paper contains a brief review
      of the current literature, basic problems, indications and operative technique.
      The authors remark, that insertion of the needle into the vertebral body gives an
      access for biopsy before cement injection. This procedure was realised in the
      case of diagnostic uncertainty. Technical details of transpedicular biopsy are
      described. The authors present 2 representative cases. FIRST CASE: a female with
      pathologic fracture of the Th7 vertebral body of osteoporotic origin. TREATMENT:
      combination of biopsy and vertebroplasty by percutaneous transpedicular approach.
      Second case: a female with cancer metastasis in L1 vertebral body, vertebroplasty
      was performed to support the anterior spinal column. Needle insertion was
      controlled either by radiofluoroscopy or by CT. The authors confirm pain relief
      related to vertebroplasty.

PMID- 11464712
TI  - [Personal modification of the Codubix prosthesis in craniofacial plastic
      surgery].
AB  - Typical "Codubix" prosthesis usually applied to cover cranial defect was used in
      craniofacial reconstruction. In this case the defect resulted from total removal
      of cranial basis neoplasm infiltrating orbital roof and surrounding structures.
      The cranial defect included right frontal bone--superciliary arch, orbital roof
      and margin; zygomatic bone frontal part junction and the lesser and greater wings
      of the sphenoid. Cranial reconstruction in this spatially differentiated area is
      technically difficult. The authors discuss the way of standard prosthesis
      modification in order to apply it in craniofacial reconstruction. Follow-up
      radiological and aesthetic results are presented.

PMID- 11464713
TI  - [Atherosclerotic changes in the aorta of patients with ischemic and hemorrhagic
      stroke].
AB  - Clinico-pathological analysis of 207 patients dying after stroke was performed.
      The occurrence of atherosclerotic lesions in the aortic arch, thoracic and
      abdominal parts of aorta were compared in patients dying of ischaemic and
      haemorrhagic stroke. Advanced atherosclerotic lesions in the arch of aorta were
      rare in patients with ischaemic and haemorrhagic stroke. Moderate atherosclerotic
      lesions in the aortic arch were observed more frequently in ischaemic than in
      haemorrhagic stroke. Advanced atherosclerotic lesions in thoracic and abdominal
      part of aorta occurred with the same frequency in ischaemic and haemorrhagic
      stroke.

PMID- 11464714
TI  - [Determination of lipoprotein (a) [Lp(a)] in patients with ischemic stroke.
      Preliminary communication].
AB  - The aim of this work was the determination of apolipoprotein(a) [Lp(a)] in the
      patients three months after the onset of ischaemic stroke. A group of 56 patients
      was investigated. Stroke was diagnosed as caused by atherosclerotic changes in
      main cerebral arteries in 32 patients and in 11 by changes in cervical arteries.
      In 13 persons a lacunar stroke was recognised. The mean Lp(a) level and the
      median value were significantly higher in the group of patients after stroke as
      compared with 45 controls. A more frequent occurrence of Lp(a) level over 30
      mg/dl considered as pathological was observed more often in the patients. No
      correlation was seen between Lp(a) and the resistance of LDL to oxidation nor
      between Lp(a) and the amount of products of LDL oxidation in vitro.

PMID- 11464715
TI  - [Tumor necrosis factor alpha (TNF-alpha) in patients with ischemic stroke].
AB  - Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine. Stroke
      induces a rapid increase in TNF-alpha levels within and around the focus of
      damaged brain. The aim of our study was to evaluate, whether patients with stroke
      differ from control patients in the concentrations of TNF-alpha in cerebrospinal
      fluid and serum. We studied TNF-alpha levels in cerebrospinal fluid and serum in
      30 patients with stroke within 24 h after onset of neurological signs and in 15
      patients of control group with the diagnosis of tension headache and
      neurasthenia. In patients with stroke the levels of TNF-alpha in the
      cerebrospinal fluid and serum were significantly higher in comparison with
      control group. The results of our study may suggest the overproduction of TNF
      alpha during first twenty-four hours of stroke.

PMID- 11464716
TI  - [Clinical course and changes of soluble interleukin-2 receptor and soluble forms
      of intercellular adhesion molecule-1 (ICAM-1) in serum of multiple sclerosis
      patients].
AB  - Changes were assessed in serum levels of soluble interleukin-2 receptor (sIL-2R
      alpha) and soluble intercellular adhesion molecule-1 (sICAM-1), indirect indices
      of activation of immunological system, in the course of multiple sclerosis (ms).
      12 patients (av. age 39.2 +/- 9.4 y.) with the first relapse that fulfilled
      criteria of clinical probable ms acc. to Poser Committee were included into the
      study. Blood samples were taken at the beginning of the relapse and then every 2
      month periods. Simultaneously, neurological impairment (EDSS scale) was assessed.
      When the next relapse occurred examination was repeated from the beginning. The
      total time of observation was between 12 and 18 months. The levels of both
      soluble molecules were examined with ELISA test. In relapse mean serum levels of
      sIL-2R alpha and sICAM-1 were significantly elevated in comparison to the results
      obtained in remission (respectively: p < 0.001 and p = 0.03). Changes in serum
      level of both soluble molecules during the first 2 months after relapse were
      significantly higher than in subsequent 2-month periods (p < 0.001). Each relapse
      was accompanied by elevation of serum levels of sIL-2R alpha and sICAM-1. There
      was no obtainable correlation between improvement in EDSS scale and changes in
      sIL-2R alpha level during the whole time of observation. Improvement in EDSS
      scale was correlated with lowering of sICAM-1 but only during the first two
      months after relapse. CONCLUSIONS: Serum level of sIL-2R alpha and sICAM-1 in ms
      patients during relapse is significantly higher in comparison to the results
      obtained during remission. Each relapse is accompanied by elevation of sIL-2R
      alpha and sICAM-1 in serum, during remission serum levels of both molecules do
      not changed significantly.

PMID- 11464717
TI  - [Surface CD2, CD4, CD8 markers and IL-2 and TNF-alpha cytokines in amyotrophic
      lateral sclerosis].
AB  - The cause of amyotrophic lateral sclerosis is still unknown. In the paper CD2,
      CD4 and CD8 markers on mononuclear cells as well as levels of TNF-alpha and IL-2
      in sera from 15 patients with ALS were evaluated. There was a significant
      increase of TNF-alpha in sera of ALS patients in comparison with control group.
      This is the first such observation. It supports the concept that immune
      mechanisms may play a role in the pathogenesis of ALS.

PMID- 11464718
TI  - [Determination of melatonin concentrations in patients with consciousness
      disturbances after craniocerebral trauma. Preliminary communication].
AB  - The study was performed in cooperation of the Department of Neurotraumatology and
      the Department of Clinical Biochemistry Jagiellonian University in Cracow. In
      patients with central nervous system injury, diagnosed upon computerized
      tomography scan, melatonin levels were measured. The most frequent reason of
      damage was severe craniocerebral trauma. Consciousness, assessed according to
      Glasgow Coma Scale, was between 3 to 13 points. Melatonin levels were measured at
      8 a.m. The investigation could not demonstrate any correlations between
      consciousness disturbances after head injury and serum melatonin levels in the
      morning. To draw a final conclusion further experiments are necessary. They will
      help to explain the role of endogenous melatonin in patients after craniocerebral
      injury.

PMID- 11464719
TI  - [The significance of stereotactic biopsy in the diagnosis and treatment of
      central nervous system lymphomas].
AB  - The paper presents seven cases of central nervous system lymphomas diagnosed in
      Department of Neurosurgery of Military Clinical Hospital in Bydgoszcz. The role
      of stereotactic biopsy in the management of this entity is underlined. Clinical,
      radiological and pathological symptoms met in PCNSL (Primary Central Nervous
      System Lymphoma) are briefly described.

PMID- 11464720
TI  - [Primary brain lymphomas].
AB  - In the Department of Neurosurgery of the Medical University of Warsaw 11 patients
      with primary central nervous system lymphomas were diagnosed and treated between
      1990 and 1999. The patients comprised of 6 females and 5 males, aged 23 to 86
      years, with most patients presenting in the sixth decade. The time from first
      symptoms to the diagnosis ranged from a few days to 5 months. In the majority of
      patients, the leading symptoms were: headaches, motor weakness, aphasia and
      memory disturbance. Initial diagnosis was based on MR in 3 patients, CT in 7 and
      on both CT and MR in 1 patient. The frontal lobe was the most common site of
      involvement. All the patients underwent surgery. The histological diagnosis was
      confirmed by immunohistochemical analysis using monoclonal antibodies: CD 20,
      CD3, CKMNF 116. In all cases, a B-cell type lymphoma was diagnosed. Radiotherapy
      was administered to 4 patients, 2 received chemotherapy and 1 received combined
      treatment. The median survival time so far is 17.6 months.

PMID- 11464721
TI  - Lab goes online seeking new blood.

PMID- 11464722
TI  - Order entry gets out of hand.

PMID- 11464723
TI  - The first steps toward security.

PMID- 11464724
TI  - I.T. shores up defenses against medication errors.

PMID- 11464725
TI  - Is the future in the cards?
AB  - Smart cards have yet to catch on in health care. Applications for data security
      and marketing, however, could boost their use.

PMID- 11464726
TI  - CIOs take time to make time.

PMID- 11464727
TI  - Exercise and heart disease.
AB  - Atherosclerotic coronary artery disease (CAD) is a leading cause of death in the
      United States. It accounts for myocardial infarction in approximately 1.5 million
      Americans annually and results in approximately 500,000 deaths yearly. Half of
      these deaths occur prior to patients being admitted to a hospital. A dramatic
      reduction in mortality related to atherosclerotic CAD has occurred in the last
      decade. This reduction has resulted from significant advances in both the medical
      and surgical management of this disease as well as from increased efforts to
      modify risk factors known to increase the likelihood of developing CAD.
      Modifiable risk factors include cigarette smoking, hypercholesterolemia, and
      hypertension. More recently, physical inactivity has been found to be a
      significant modifiable risk factor that can influence the development of CAD.
      This article reviews some of the observational data that support these
      conclusions, discusses the role of exercise in the prevention of CAD in select
      groups, and reviews some of the mechanisms by which exercise may modify the
      development of CAD.

PMID- 11464728
TI  - The preparticipation physical examination.
AB  - For decades the preparticipation physical examination (PPE) has been used to
      screen athletes prior to sports participation to prevent injury or illness.
      Evolution of the PPE, it is theorized, originated from the need to identify
      individuals with conditions that may predispose them to injuries or life
      threatening situations. However, the effectiveness, practicality, and worthiness
      of the examination are a matter of debate. As members of a medical team,
      physicians are responsible for the health and safety of the athlete. The PPE is
      the first step in satisfying this responsibility. This article discusses the
      components of the PPE and presents the evidence-based model of knowledge behind
      the PPE.

PMID- 11464729
TI  - Assessment and management of the painful shoulder.
AB  - The shoulder joint is a complex structure composed of intricate bony architecture
      and an ornate system of muscles, tendons, and ligaments. What many refer to as
      the "shoulder joint" is actually a combination of 4 articulations--the
      glenohumeral joint, acromioclavicular joint, sternoclavicular joint, and the
      scapulothoracic articulation. These structures work together to provide the
      shoulder complex with multiple degrees of freedom, which allow the upper
      extremity to be abducted, adducted, rotated, flexed, and extended. Although this
      flexibility is vital for positioning the arm in space, it can make the evaluation
      of pathology difficult. Furthermore, neck pathology can refer pain to the
      shoulder, which may require a screening evaluation of the neck. This article
      reviews the relevant anatomy and discusses an approach to the differential
      diagnosis of shoulder pain.

PMID- 11464730
TI  - The sprained ankle.
AB  - The sprained ankle is the most common musculoskeletal injury seen by physicians
      caring for active youngsters and adults. It accounts for approximately one fourth
      of all sports-related injuries and is commonly seen in athletes participating in
      basketball, soccer, or football. It has been shown that one third of West Point
      cadets suffer an ankle sprain during their 4 years at the military academy. While
      diagnosis and management of the sprained ankle is usually straightforward,
      several serious injuries can masquerade as an ankle sprain, and it is important
      for the clinician to recognize these to prevent long-term morbidity. In this
      article the basic anatomy of the ankle, mechanisms by which the ankle is injured,
      and the differential diagnosis of the acutely injured ankle are reviewed.
      Appropriate evaluation of the injured ankle and the criteria that should be
      utilized for determining the necessity of radiographs are discussed as well as
      management of the acutely sprained ankle and the role of prevention in reducing
      the risk of ankle injury.

PMID- 11464731
TI  - Understanding NSAIDs: from aspirin to COX-2.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) annually account for 70 million
      prescriptions and 30 billion over-the-counter (OTC) medications sold in the
      United States alone. Despite our familiarity with these drugs, NSAIDs are full of
      paradoxes that pose significant challenges for the medical community. Although
      NSAIDs are among the oldest of drugs, new formulations continue to come to
      market. Some formulas are safe enough to be sold OTC for use in infants with
      fever, while others are available only as a prescription medication and are a
      leading cause of iatrogenic reactions, hospitalizations, and death. Physicians
      face the choice of prescribing lower cost, older NSAIDs versus the more expensive
      but potentially safer ones. The use of NSAIDs is clearly increasing. Factors
      contributing to this increase are the availability of OTC preparations and the
      aging of the population with a concomitant increase in osteoarthritis. One
      indication of the popularity of NSAIDs is that following the introduction of 2
      new cyclooxygenase-2 (COX-2) selective inhibitors in 1999, these drugs
      immediately became the most frequently prescribed new drugs in the United States.
      This article will familiarize the practitioner with the various types of NSAIDs,
      including the newer COX-2 formulations, their mechanism of action, and potential
      adverse reactions and efficacy. Although most practitioners are aware of the
      indications for NSAIDs, research is continuing to explore nontraditional
      applications. A new framework is being created that will allow new additions to
      the NSAID class of medications.

PMID- 11464732
TI  - Teenage births to ethnic minority women.
AB  - This article analyses British age-specific fertility rates by ethnic group, with
      a special interest in child-bearing by women below the age of 20. Birth
      statistics are not analysed by ethnic group, and teenage birth rates have been
      estimated from the dates of birth of mothers and children in the Labour Force
      Survey. The method appears to be robust. Caribbean, Pakistani and especially
      Bangladeshi women were much more likely to have been teenage mothers than white
      women, but Indian women were below the national average. Teenage birth rates have
      been falling in all three South Asian communities.

PMID- 11464733
TI  - Adoptees and relatives who wish to contact one another: the Adoption Contact
      Register.
AB  - The article describes the background to the introduction of the Adoption Contact
      Register, what it does, and the numbers of adoptees and relatives who have used
      it since 1991. The article also considers the profile of relationships of the
      relatives to the adoptees--and compares the profile of these relationships
      amongst successful matches with the profile of relationships amongst all
      relatives on the Register.

PMID- 11464734
TI  - The proportion of adoptees who have received their birth records in England and
      Wales.
AB  - Over 70 thousand adults who were adopted in out-of-family adoptions have received
      their original birth records from ONS since The Children Act, 1975 (Section 26)
      first enabled them to do so. This article describes how estimates of these
      adoptees have been made by their year of birth and year of receiving their birth
      record. It then analyses the trends, with particular reference to the theory that
      adoption can cause deep-seated psychological problems, setting them within the
      historical context of adoption in this century.

PMID- 11464735
TI  - The demographic situation in the European Union.
AB  - This article draws selected material from the annual Yearbook on Demography (2000
      edition) published by Eurostat, the Statistical Office of the European
      Communities. Some key comparisons with other regions of the world are included,
      together with a broad picture of the demographic situation in the European Union.
      Topic coverage is selective.

PMID- 11464736
TI  - New methods for the detection of viruses: call for review of drinking water
      quality guidelines.
AB  - Drinking water supplies which meet international recommendations for source,
      treatment and disinfection were analysed. Viruses recovered from 100 L-1,000 L
      volumes by in-line glass wool filters were inoculated in parallel into four cell
      culture systems. Cell culture inoculation was used to isolate cytopathogenic
      viruses, amplify the nucleic acid of non-cytopathogenic viruses and confirm
      viability of viruses. Over a period of two years, viruses were detected in 23% of
      413 drinking water samples and 73% of 224 raw water samples. Cytopathogenic
      viruses were detected in 6% raw water samples but not in any treated drinking
      water supplies. Enteroviruses were detected in 17% drinking water samples,
      adenoviruses in 4% and hepatitis A virus in 3%. In addition to these viruses,
      astro- and rotaviruses were detected in raw water. All drinking water supplies
      had heterotrophic plate counts of < 100/mL, total and faecal coliform counts of
      0/100 mL and negative results in qualitative presence-absence tests for somatic
      and F-RNA coliphages (500 mL samples). These results call for a revision of water
      quality guidelines based on indicator organisms and vague reference to the
      absence of viruses.

PMID- 11464737
TI  - Climatic effects on Salmonella survival in plant and soil irrigated with
      artificially inoculated wastewater: preliminary results.
AB  - The use of wastewater to replace other water resources for irrigation is highly
      dependent on whether the health risk and environmental impacts entailed are
      acceptable or not. Total count and species of microorganisms found in wastewater
      vary widely because of climatic conditions, season, population sanitary habits
      and disease incidence. Salmonella, one of the genera associated with waterborne
      diseases, lives in the intestine. Thus, it is widely accepted that they have a
      limited survival period under environmental conditions. Wastewater management
      practices and the ability of Salmonella to survival under field conditions would
      determine the health risk associated with its presence in wastewater. Although
      chlorination is widely used, there are situations in which Salmonella is able to
      survive the sudden stress imposed by this technique. The aim of this experiment
      was to contribute to the study of the climatic and soil effects on pathogen
      survival under agricultural field conditions in order to assess which were the
      best wastewater management practices from both health and economic points of
      view. Five pots filled with soil seeded with Medicago sativa and an automatic
      weather station were used. A secondary effluent was artificially inoculated with
      Salmonella. In addition, open plates (filled with sterilised soil) and
      ultraviolet radiation isolated plates (filled with non-sterilised soil) were
      used. As soil heat emission contributes to the environmental conditions around
      the bacteria, standardised meteorological temperature data had to be carefully
      used in the bacterial survival studies under agricultural conditions. Radiation
      was the main cause of Salmonella mortality as its effect was more important than
      natural soil bacteria competence. Higher reduction of Salmonella counts could
      have been associated with longer spring days. Soil was able to effectively remove
      Salmonella. Subsurface drip irrigation methods could provide an effective tool to
      prevent health risk associated with wastewater irrigation.

PMID- 11464738
TI  - Experimental investigations and numerical modelling of Cryptosporidium parvum
      transport behaviour in aquifers.
AB  - The purpose of this study was to improve understanding of the potential for
      transfer of the protozoan pathogen Cryptosporidium parvum through aquifers to
      drinking water wells. Therefore, the factors characterising this transport were
      experimentally determined. We have developed a continuously recirculating column
      assay. The latter allows small amounts of C. parvum oocysts to be manipulated
      providing as much protection as possible from the risks of contamination. As the
      analysis of oocyst samples is time consuming, a numerical model, simulating the
      transport phenomena of oocysts under the experimental conditions of assays, was
      developed to establish the whole experimental curve of results using a small
      number of experimental points. The comparisons drawn between analytic solutions,
      experimental results with tracer (NaCl solution) and numerical simulation were in
      good agreement. A continuously recirculating column assay was performed using
      oocysts in suspension (flow rate = 1.43 mL/min). Treated sand was used as
      previous experiments had shown that no adsorption occurs. We observed almost
      total filtration (99.85%). To check this result, an assay with an open column was
      carried out under the same conditions. We observed a filtration value of 97%.
      Consequently, we may say that the continuously recirculating column assay
      provides satisfactory results.

PMID- 11464739
TI  - Adsorption and survival of faecal coliforms, somatic coliphages and F-specific
      RNA phages in soil irrigated with wastewater.
AB  - This study was carried out to compare the adsorption and survival of faecal
      coliforms, somatic coliphages and F-specific RNA phages in soil irrigated with
      wastewater. Adsorption isotherms showed that 3-10x more faecal coliforms than
      somatic coliphages were adsorbed from wastewater onto soil. The adsorption
      behavior of F-specific RNA phages was intermediate between those of these two
      microorganisms. In wastewater, the inactivation factor of somatic coliphages at 8
      22 degrees C was 5-7 lower than those of faecal coliforms. F-specific RNA phages
      have a decrease close to faecal coliforms. In soil, at temperatures of 8-22
      degrees C and at moistures of 15-35%, somatic coliphages survived longer than the
      two other microorganisms. These results seemed to be confirmed by the soil column
      experiments. The rate of inactivation of all microorganisms was lower in soil
      than in wastewater and depended extensively on soil temperature and moisture
      content. Survival was optimal at low temperature (8 degrees C) and low moisture
      content (15%). Thus, somatic coliphages seemed to be a better indicator of faecal
      contamination than faecal coliforms under our experimental conditions and based
      only on the two criteria tested (survival and adsorption). Somatic coliphages
      were able to contaminate the soil over greater distances and survive better in
      both wastewater and soil than faecal coliforms. These results need to be
      confirmed by studies on several soil columns using different kinds of soil and
      different kinds of wastewater.

PMID- 11464740
TI  - Neural network modelling of Cryptosporidium and Giardia concentrations in the
      Delaware River, USA.
AB  - Artificial neural networks are brain-like structures used in mathematical
      modelling that excel in pattern recognition. In this research, a simple feed
      forward artificial neural network, trained by error back-propagation algorithm,
      was used as a tool to relate peak Cryptosporidium and Giardia concentrations with
      other biological, chemical and physical parameters in surface water. Multiple
      water quality parameters at a water treatment plant intake on the Delaware River,
      New Jersey, USA, collected in 1996, were provided to the authors for recognition
      analysis. Water samples were classified as "background" and "above background"
      based on the concentration of full and empty oocysts and cysts of Cryptosporidium
      and Giardia. The results of this preliminary effort were encouraging. Parameters
      significant to the identification of each protozoa were identified, eight for
      Cryptosporidium and seven for Giardia by a stepwise elimination technique. Data
      withheld from the model training was used to validate the trained models and
      evaluate the most effective internal architecture. In both cases, the best
      prediction performance was found when the number of internal nodes was twice that
      of the input parameters in single hidden-layer architecture. Predictions for the
      classification of the verification data set resulted in no false-negatives (mis
      prediction of above background protozoa concentrations) when the models were
      optimally trained.

PMID- 11464741
TI  - Persistence of two model enteric viruses (B40-8 and MS-2 bacteriophages) in water
      distribution pipe biofilms.
AB  - The persistence of two model enteric virions (Bacteroides fragilis phage B40-8
      and coliphage MS-2) within pipe biofilms was investigated in situ in an urban
      distribution system. Biofilms were allowed to develop on uPVC and stainless steel
      (SS) coupons in a modified Robbins' device for 70 d within a 150 mm uPVC
      reticulation main. Coupons were then placed in annular reactors and slug dosed
      with B40-8 and MS-2 phages (10(8) pfu/mL). Pipe water velocity, pH and free
      chlorine were recorded during the experimental period. Biofilms on uPVC were
      generally more abundant (based on total bacterial counts, HPCs, total protein and
      total carbohydrate). Both B40-8 and MS-2 were incorporated into biofilms formed
      on uPVC and SS coupons (> 10(4) and > 10(3) pfu/microgram protein respectively)
      and persisted for > 30 d and 6 d respectively, reflecting biofilm biomass on the
      two pipe surfaces. Virion loss/inactivation from biofilm followed an initial
      rapid phase, followed by a very slow phase representing approximately 0.01% of
      the original virion population. Virions, therefore, have the potential to
      accumulate within distribution biofilm and problems could arise when clusters of
      biofilm-associated enteric virions become detached from the substrata by
      hydrodynamic forces or sudden changes in disinfection regime.

PMID- 11464742
TI  - Comparative survival of enteric viruses and bacteria in Atlantic Ocean seawater.
AB  - The survival of Escherichia coli, Salmonella typhi, Shigella sonnei, poliovirus
      type 1 and a parvovirus (Minute Virus of Mice) was determined in seawater. Seeded
      seawater was incubated in the laboratory at 6, 12, 20 and 28 degrees C for up to
      40 d. In-situ survival studies were done seasonally (winter, spring, summer and
      fall) using seeded microbial dialysis equipment placed in the Atlantic Ocean off
      coastal North Carolina at water depths of 3-10 m. In laboratory studies all test
      microbes survived longer at lower temperatures with typical times for 90%
      inactivation (T90) of 1-3 d at the highest temperature and > 10 d at the lowest
      temperature. Of the microbes tested, E. coli survived least well while S. typhi
      and Sh. sonnei survived similar to or greater than enteric viruses. Parvovirus
      survival was similar to that of poliovirus. Under in-situ conditions, E. coli
      also survived least well of all microbes tested with T90 values of 0.9-3.9 d
      depending upon season. All other test microbes had generally similar survivals.
      Overall, microbial survival in seawater was greater under laboratory conditions
      than under in-situ conditions. There was no clear association between microbial
      survival and water temperature. The lower survival of E. coli compared to the
      bacterial and viral pathogens under laboratory conditions raises concerns because
      it is a key microbial indicator of faecal contamination.

PMID- 11464743
TI  - Runoff of faecal microorganisms and nutrients from perennial grass ley after
      application of slurry and mineral fertiliser.
AB  - Perennial grass was fertilised with cattle slurry either surface-spread or
      injected into the soil. Slurry was spread once (early summer) in 1996 and 1997
      and twice (both summer and autumn) in 1998 and 1999. The control was mineral
      fertilisation in summer. Faecal microbial numbers in surface runoff water were
      very high in late June 1998 soon after very heavy rains even though the last
      slurry application had been made almost one year earlier. There was no clear
      difference between slurry spreading methods. Autumn spreading of slurry lead to
      high microbial levels in runoff waters and water hygiene was protected better by
      slurry injection than by surface spreading. In spring, after snow melt, some
      faecal microorganisms were found in surface runoff water and the numbers of
      faecal microorganisms were less from plots with slurry surface spreading than
      those with slurry-injection. Losses of total phosphorus (TP) and total nitrogen
      (TN) in surface runoff were 2.7 and 7.7 kg/ha respectively from grass with
      surface-spread slurry in winter 1998-1999. The injection of slurry decreased TP
      and TN runoff by an average of 81% and 73% respectively. In 1999 there was little
      runoff because the summer was sunny and dry.

PMID- 11464744
TI  - Comparison of static and dynamic disinfection models for bacteria and viruses in
      water of varying quality.
AB  - Disinfection studies rarely use natural waters due to demands exerted on the
      applied disinfectants and lack of consistent disinfectant residuals. This study
      compared the degree of disinfection achieved in natural waters between
      conventional batch (static) models and a system of similar volume where
      disinfectant residuals were maintained at constant levels (dynamic). In the
      latter, disinfectant was delivered through a hollow fibre cartridge from a
      slipstream of a full-scale (chloramine) or pilot (chlorine) water treatment
      plant. The test organisms (hepatitis A virus, poliovirus, MS-2, Mycobacterium
      terrae and Enterococcus durans) were selected with different resistance to the
      disinfectants. In general, for water of "good" quality, the differences between
      the two systems were often small or not apparent for monochloramine. However, for
      low chlorine residuals, or when additional demand was placed on the disinfectant,
      differences between the two systems became more apparent. Little difference was
      seen between disinfection of the test organisms singly or in mixtures, but injury
      of vegetative bacteria with monochloramine was very apparent. This system could
      be useful for understanding the fluctuations in disinfection efficacy that may
      occur in source water of varying quality, or in distribution systems, as
      disinfectant residuals decline.

PMID- 11464745
TI  - Synergistic effect of solar radiation and solar heating to disinfect drinking
      water sources.
AB  - Waterborne diseases are still common in developing countries as drinking water
      sources are contaminated and feasible means to reliably treat and disinfect these
      waters are not available. Many of these developing countries are in the tropical
      regions of the world where sunlight is plentiful. The objective of this study was
      to evaluate the effectiveness of combining solar radiation and solar heating to
      disinfect contaminated water using a modified Family Sol*Saver System (FSP). The
      non-UV transmittable cover sheet of the former FSP system was replaced with an UV
      transmittable plastic cover sheet to enable more wavelengths of sunlight to treat
      the water. Disinfection efficiency of both systems was evaluated based on
      reduction of the natural populations of faecal coliform, E. coli, enterococci, C.
      perfringens, total heterotrophic bacteria, hydrogen sulphide producing bacteria
      and FRNA virus. The results showed that under sunny and partly sunny conditions,
      water was heated to critical temperature (60 degrees C) in both the FSP systems
      inactivating more than 3 log (99.9%) of the concentrations of faecal coliform and
      E. coli to undetectable levels of < 1 CFU/100 mL within 2-5 h exposure to
      sunlight. However, under cloudy conditions, the two FSP systems did not reduce
      the concentrations of faecal indicator bacteria to levels of < 1 CFU/100 mL.
      Nonetheless, sufficient evidence was obtained to show that UV radiation of
      sunlight plus heat worked synergistically to enhance the inactivation of faecal
      indicator bacteria. The relative log removal of indicator microorganism in the
      FSP treated water was total heterotrophic bacteria < C. perfringens < F RNA virus
      < enterococci < E. coli < faecal coliform. In summary, time of exposure to heat
      and radiation effects of sunlight were important in disinfecting water by solar
      units. The data indicated that direct radiation of sunlight worked
      synergistically with solar heating of the water to disinfect the water. Thus,
      effective disinfection was observed even when the water temperature did not reach
      60 degrees C. Finally, the hydrogen sulphide test is a simple and reliable test
      that householders can use to determine whether their water had been sufficiently
      disinfected.

PMID- 11464746
TI  - The effect of temperature on the efficacy of ozonation for inactivating
      Cryptosporidium parvum oocysts.
AB  - Examination of the effects of water temperature on the inactivation of
      Cryptosporidium parvum oocysts with ozone, ozonation experiments were conducted
      in a semi-batch mode with a wide temperature range of 3-30 degrees C.
      Inactivation was assessed in terms of mice infectivity and in vitro excystation.
      The temperature dependency of the CT products by a reduction in infectivity of 2
      log10 could be described successfully by the Arrhenius equation, 1/CT = 1.086 x
      10(18)e-12520/K where CT is the integrated ozone concentration over the contact
      time (mg/min/L) and K is the Kelvin temperature of water. As for the reduction in
      viability assessed by the excystation assay, protocol B, the obtained regression
      equation, 1/CT = 1.802 x 10(18)e-12640/K, was almost identical to that observed
      for the infectivity. Thus, the CT products required for a 2 log10 reduction in
      both infectivity and viability increased by an average factor of 4.2 for every 10
      degrees C decrease in water temperature. Additionally, our findings suggested
      that the viability, as determined by protocol B, could substitute for animal
      infectivity in evaluating the effects of environmental factors on the efficacy of
      ozonation.

PMID- 11464747
TI  - Inactivation of Cryptosporidium parvum oocysts with sequential application of
      ozone and combined chlorine.
AB  - Single-step inactivation experiments with ozone and monochloramine revealed the
      presence of a CT lag followed by pseudo-first order inactivation kinetics.
      Sequential disinfection experiments with ozone followed by monochloramine
      revealed that ozone pretreatment resulted in the removal of a more prominent CT
      lag observed for monochloramine. In addition, the rate of inactivation for ozone
      pretreated oocysts was approximately 2.5x greater than that observed for the post
      lag phase portion of the monochloramine primary inactivation curve.

PMID- 11464748
TI  - Comparative effectiveness of UV wavelengths for the inactivation of
      Cryptosporidium parvum oocysts in water.
AB  - Cryptosporidium parvum oocysts in water were exposed to distinct wavelength bands
      of collimated beam ultraviolet (UV) radiation across the germicidal UV wavelength
      range (210-295 nm) that were emitted from a medium pressure (MP) mercury vapour
      lamp. The dose of UV radiation transmitted though each narrow bandpass filter was
      measured utilising potassium ferrioxalate actinometry. Oocyst infectivity was
      determined using a cell culture assay and titre was expressed as an MPN. The
      log10 inactivation for each band of radiation was determined for a dose of 2
      mJ/cm2. Doses from all wavelengths between 250-275 nm resulted in approximately 2
      log10 inactivation of Cryptosporidium parvum oocyst infectivity while doses with
      wavelengths higher and lower than this range were less effective. Because
      polychromatic radiation from MP UV lamps had about the same germicidal activity
      between the wavelengths of 250-275 nm for inactivation of oocyst infectivity,
      there was no unique advantage of MP UV over low pressure (LP) UV except for the
      simultaneous delivery of a wide range of germicidal wavelengths.

PMID- 11464749
TI  - Disinfection of secondary effluents by infiltration percolation.
AB  - Among the most attractive applications of reclaimed wastewater are: irrigation of
      public parks, sports fields, golf courses and market gardening. These uses
      require advanced wastewater treatment including disinfection. According to WHO
      guidelines (1989) and current rules and regulations in Tunisia, faecal coliform
      levels have to be reduced to < 10(3) or 10(2) CFU/100 mL. In Tunisia, most
      wastewater plants are only secondary treatment and, in order to meet health
      related regulations, the effluents need to be disinfected. However, it is usual
      for secondary effluents to need filtration prior to disinfection. Effectiveness
      of conventional disinfection processes, such as chlorination and UV radiation,
      are dependent upon the oxidation level and the levels of suspended solids of the
      treated water. Ozonation is relatively expensive and energy consuming. The
      consideration of the advantages and disadvantages of conventional techniques,
      their reliability, investment needs and operational costs will lead to the use of
      less sophisticated alternative techniques for certain facilities. Among
      alternative techniques, soil aquifer treatment and infiltration percolation
      through sand beds have been studied in Arizona, Israel, France, Spain and
      Morocco. Infiltration percolation plants have been intermittently fed with
      secondary or high quality primary effluents which percolated through 1.5-2 m
      unsaturated coarse sand and were recovered by under-drains. In such infiltration
      percolation facilities, microorganisms were eliminated through numerous physical,
      physicochemical and biological inter-related processes (mechanical filtration,
      adsorption and microbial degradation respectively). Efficiency of faecal coliform
      removal was dependent upon the water detention times in the filtering medium and
      on the oxidation of the filtered water. Effluents of Sfax town aerated ponds were
      infiltrated through 1.5 m deep sand columns in order to determine the performance
      of infiltration percolation in the polishing of secondary effluents. Elimination
      of bacteria (total and coliforms, faecal streptococci) and their relationship
      with the hydraulic load and the temperature were investigated.

PMID- 11464750
TI  - The elimination of helminth ova, faecal coliforms, Salmonella and protozoan cysts
      by various physicochemical processes in wastewater and sludge.
AB  - The removal of helminth ova, faecal coliforms, Salmonella and protozoan cysts by
      the application of physicochemical treatment processes to municipal wastewater
      and sludge was studied. In the first case, the advanced primary treatment (APT)
      process was studied, as well as filtration of the APT effluent. The APT sludge
      was treated with either lime or acid. The initial values of helminth ova, faecal
      coliforms, Salmonella and protozoan cysts in the wastewater were 23-27 eggs/L,
      7.8 x 10(7)-6.5 x 10(8) MPN/100 mL, 4.5 x 10(5)-2.4 x 10(6) MPN/100 mL, and 1,007
      1,814 cysts/L respectively. After APT treatment, 96% of the helminth ova, 1 log
      of faecal coliforms and Salmonella, and 67% of the protozoan cysts were
      eliminated. To reduce the concentration of helminth ova from values > 1.2 ova/L
      to < 1 ova/L an additional filtration step was required. In the sludge, the
      initial values of helminth ova, faecal coliforms and Salmonella were 65-120 ova/g
      TS, 8.3 x 10(7)-1.4 x 10(11) MPN/g TS and 3.6 x 10(6)-2.4 x 10(10) MPN/g TS
      respectively. A 97% reduction of the helminth and an 8.5 log reduction of faecal
      coliforms and Salmonella was achieved by alkaline stabilisation, compared with a
      98% and 4.5 log reduction by acid treatment.

PMID- 11464751
TI  - Occurrence of Cryptosporidium in Japan and counter-measures in wastewater
      treatment plants.
AB  - The outbreak of cryptosporidiosis in Ogose in 1996 forced the wastewater
      treatment authorities to rethink the level of contamination by Cryptosporidium of
      wastewater and waters in the watersheds and counter-measures in wastewater
      treatment plants. A survey of Cryptosporidium concentrations in wastewater and
      treated wastewater conducted nationwide showed relatively low levels. Also,
      evaluation of wastewater treatment showed a 2 log oocyst removal with an
      activated sludge process and an additional 1 log removal with coagulant dosing.

PMID- 11464752
TI  - Water quality improvement of treated wastewater by intermittent soil percolation.
AB  - Our research aimed to evaluate intermittent soil infiltration of treated sewage
      for reuse in the north of Chile. Aerated lagoon effluent was infiltrated in
      columns packed with native soils (sandy-lime, lime-gravel and limey-sand).
      Columns were operated for more than a year under different cycles of filling and
      drying, depths and load pressures depending on soil characteristics. The
      efficiency of the system was determined through influent-effluent microbiological
      indicators level (faecal coliforms, E. coli, Salmonella spp, MS2 phage, and
      protozoan cysts), physicochemical characterisation (TOC, COD, BOD, nitrogen), and
      hydraulic flow measurement. Results showed: (a) high reduction of enteric
      bacteria (5-7 log10), some inactivation of phage (2-4 log10) and complete removal
      of intestinal cyst; (b) stable removal of organic matter (80-90% reduction of
      TOC, COD, BOD); and (c) partial ammonia reduction through adsorption and
      nitrification with denitrification mainly occurring in sandy soil. Preliminary
      data from pilot plant working in the field showed better results that those
      obtained in the laboratory especially removal of microbiological indicators.
      Microbiological quality of effluent met Class A regulations for agricultural
      reuse (WHO, 1989) and the system looks like an attractive alternative to cope
      with water shortage in the region.

PMID- 11464753
TI  - Correlations between microbial parameters from water samples: expectations and
      reality.
AB  - Data which are collected in order to estimate the correlation between parameters
      must be analysed with caution. Classical statistics of correlation are often
      inappropriate. The "r" statistic is very easily distorted by non-Normal data. Non
      parametric statistics can be helpful. The interpretation and usefulness of the
      estimates of correlation will depend on the study plan. If water samples come
      from disparate sources (e.g. upstream or downstream from sewage outlets) then
      parameters A and B may occur in their highest and lowest numbers according to how
      close the samples were to contamination sources thus correlating closely.
      However, if all samples come from sources with similar pollution levels then
      plots of A and B will show considerable scatter and apparently little
      correlation. So what is the relationship between A and B? An example of "perfect"
      correlation, as demonstrated by replicate counts of a single parameter from split
      samples, gave an r value of only 0.63 (p = 0.62) due to random variation in
      numbers of organisms between the two halves of the sample. Thus large amounts of
      data are needed for studying true correlation because relationships between
      parameters are embedded in the natural variation. This also illustrated that
      Standards for a single parameter can be "passed" or "failed" by two halves of the
      same sample. Study design is clearly of fundamental importance. Consideration
      must be given to the appropriate way of asking questions about correlation
      between different parameters.

PMID- 11464754
TI  - Behaviour of pathogenic E. coli and Salmonella enteritidis in small domestic
      sewage treatment apparatus ("Johkasou").
AB  - "Johkasou" is a small sewage treatment apparatus commonly used in Japan which can
      effectively treat domestic wastewater in places where a public sewage system is
      difficult to supply. The behaviour of enterohaemorrhagic E. coli O157 and
      Salmonella enteritidis in a "Johkasou" was studied. Their reduction rates
      depended significantly on the water temperature in the "Johkasou" with minimal
      decrease in numbers at 10 degrees C within 48 h. The reduction rates increased at
      20 degrees C and 30 degrees C where 4 log reduction could be expected. The
      reduction rates were influenced by the BOD of the solutions that contained the
      pathogens with the lower the BOD the higher the reduction rate. The reduction
      rates were about the same between both pathogens. The result showed that it was
      necessary to disinfect the effluent as some pathogens can pass through the
      apparatus when some users of the apparatus excrete pathogens.

PMID- 11464755
TI  - The effect of liming on the microbiological quality of urban sludge.
AB  - Treatments applied to sludge in order to stabilise and dehydrate them may give
      notable inactivation of microorganisms. This is observed when sludge is exposed
      either to high temperature or drastic pH when residual sludge is limed. The
      control of virological, parasitological and bacteriological sludge quality by
      detecting pathogenic microorganisms is slow and too expensive to be commonly
      practised. Thus, it is possible to replace pathogenic microorganisms detection by
      that of contamination indicators. The aim of this study was to determine the
      influence of liming on the behaviour of pathogenic microorganisms detected in
      urban sludge. The detection of Salmonella and helminth eggs was carried out in
      liquid sludge (2-3% dryness) and solid sludge (23% dryness) with added lime (0
      45% weight/dry weight) and stored for 24 h-46 weeks. The results showed that
      liming modified some characteristics such as temperature, dryness and pH of the
      sludge. It appeared that, whatever the percentage of added lime, the temperature
      of liquid sludge did not change while it increased by about 9 degrees C when 30
      45% lime was added to solid sludge. In the same way, the dryness of liquid sludge
      did not change during the liming, whereas the dryness of 45% limed solid sludge
      increased from 23% to 31%. Finally, 15%, 30% and 45% liming gave a pH of at least
      10, 11.5 and 12, respectively, although the pH increase depended on the sludge
      type. The efficiency of liming was considered to be related to the pH and not to
      the percentage of added lime. Three factors determined the efficiency of pathogen
      elimination: (a) the pH reached by the sludge, (b) the period of liming activity
      and (c) the dryness of the sludge. Salmonella were eliminated from liquid sludge
      in 24 h at pH 10.7 and from solid sludge in 24 h at pH 10.0. Viable helminth egg
      concentration decreased to 3 eggs/10 g DM in liquid sludge in 14 d at pH 11.9 and
      60 d at pH 11.6. In solid sludge, egg reduction was achieved in 24 h at pH 12.5,
      7 d at pH 12.0 and 14 d at pH 11.5. From this study, it appeared that liming
      resulted in a much better microbiological quality of liquid sludge if its pH was
      maintained at 11.6 over 60 d or at pH 11.9 for 14 d. Solid sludge needed to be
      maintained at pH 11.5 for 14 d, pH 12.0 for 7 d or pH 12.5 for 24 h to achieve
      similar results.

PMID- 11464756
TI  - Evaluation of fluorogenic TSC agar for recovering Clostridium perfringens in
      groundwater samples.
AB  - Clostridium perfringens is widely recognised as a reliable water pollution
      indicator. Since several media can be employed for the membrane filtration
      enumeration of this microorganism, the main aim of this work was to investigate
      the ability of fluorocult-supplemented TSC-agar (Merck) for recovering Cl.
      perfringens from public springs used for direct human consumption. Cl.
      perfringens recovery was also performed on mCP agar (Cultimed) according to
      Directive 98/83 as well as on TSC-Agar (Merck), TSN-Agar (Merck) and SPS-Agar
      (BBL) media. Variance analysis of data obtained showed no statistically
      significant differences in the counts obtained among all media employed in this
      work. However, the Cl. perfringens recovery efficiencies with TSC and fluorogenic
      TSC agars were significantly greater (P = < 0.05) than the corresponding values
      of mCP and TSN media. On the other hand, the identification of typical and
      atypical colonies isolated from all media demonstrated that fluorogenic TSC agar
      was the most specific medium for Cl. perfringens recovery in groundwater samples
      (85.3% of typical colonies and 82.8% of atypical colonies confirmed). In summary,
      the membrane filtration technique with fluorogenic TSC agar showed the best
      performance characteristics of all the media tested as judged by their recovery
      efficiency and specificity in these water samples.

PMID- 11464757
TI  - Optimisation of the ISO-method on enumeration of somatic coliphages (draft ISO
      10705-2).
AB  - As part of the EU project "Bacteriophages in Bathing Waters" (January 1996-June
      1999) research was carried out to optimise the method for detection and
      enumeration of somatic coliphages in water as described in ISO/CD 10705-2 of
      August 1995. It was concluded that this draft ISO standard needed to be amended
      in certain aspects. For determining the viable count of the host culture WG5
      Escherichia coli, a membrane filtration technique should be used instead of
      spread plate technique as the latter gives lower and less reproducible results. A
      freshly prepared inoculum culture of host strain WG5 should be used instead of a
      frozen inoculum culture as freezing of the inoculum culture is found to
      negatively influence the phage counts. The double agar layer method (DAL) is
      preferred to the single agar layer method (SAL) for performing the phage analysis
      as the DAL method gives higher phage counts than the SAL method.

PMID- 11464758
TI  - Detection and rapid differentiation of human enteroviruses in water sources by
      restriction enzyme analysis.
AB  - The objective of this study was to assess the application and efficiency of
      molecular techniques for the detection and serotyping of enteroviruses from
      environmental water samples. Samples of water were collected at regular intervals
      upstream and downstream of an informal settlement. Techniques for the detection
      of enteroviruses included a reverse transcription polymerase chain reaction (RT
      PCR), nested PCR (n-PCR) and Sabin-specific triplex PCR. A specific 297 bp
      fragment was amplified by the n-PCR and subjected to restriction enzyme (RE)
      analysis to differentiate between various serotypes of prototypical
      enteroviruses. Enteroviruses that gave inconclusive restriction patterns were
      typed by partial sequencing of the VP1 region. Results indicated a high incidence
      of enteroviruses, predominantly coxsackie B viruses. The results on polioviruses,
      as well as other enteroviruses, contributed valuable information on enteroviruses
      circulating in the community. The molecular approach described here proved
      suitable for the rapid, sensitive, specific and cost effective, simultaneous
      detection and typing of enteroviruses in water.

PMID- 11464759
TI  - Evaluation of Coli-ID and MUG Plus media for recovering Escherichia coli and
      other coliform bacteria from groundwater samples.
AB  - Several chromogenic media for detecting coliform bacteria in water are
      commercially available including Coli ID medium (ID) (bioMerieux) and MUG Plus
      cefsulodin agar (MP) (Laboratorios Microkit, S.L.). Since little is known about
      the performance of these media, we have evaluated their usefulness for recovering
      Escherichia coli and other coliform organisms in groundwaters used for direct
      human consumption. Variance analysis of obtained data showed that no
      statistically significant differences in counts of E. coli and other coliforms on
      ID and MP media compared with reference methods. However, the evaluation of
      sensitivity and recovery efficiency of both media showed that the two chromogenic
      media were more sensitive and significantly more efficient (P = < 0.05) than
      reference medium for detecting coliforms in groundwater. However, the
      identification of 400 typical and atypical colonies isolated from ID and MP media
      demonstrated a higher specificity when using ID for coliforms and E. coli. In
      summary, the two chromogenic media evaluated could be used as alternative methods
      to reference media for detecting and recovering coliform bacteria in groundwater
      samples. MP agar was more sensitive and efficient than ID agar whereas the latter
      was more specific and selective.

PMID- 11464760
TI  - Early warning of faecal contamination of water: a dual mode, automated system for
      high- (< 1 hour) and low-levels (6-11 hours).
AB  - There is a recognised need for methods that permit rapid estimation of the
      sanitary quality of water e.g. during raw water monitoring and emergencies
      involving water treatment failure or main breaks in a distribution network. In
      this study, two models for predicting the level of faecal contamination of water
      were studied. The first format, based on measurement of beta-galactosidase
      activity by the automated Colifast analyser, detected faecal contamination of
      high levels, corresponding to > 15 thermotolerant coliforms (FC)/5 mL, in 1-3 h,
      in a format that allowed for semi-quantification of results. By setting up a cut
      off level, the system could be used as an operational tool identifying random
      increases in faecal contamination during routine raw water monitoring. A second
      Presence-Absence format was dependent upon the growth of low levels of FC with
      subsequent detection in the Colifast analyser. 95% of water samples containing 1
      15 FC/sample volume showed positive detection after 11 h.

PMID- 11464761
TI  - Determination of salmonellae from municipal wastewaters.
AB  - This study compared the efficiency of culture methods for salmonellae detection
      in wastewaters collected from three Finnish municipal treatment plants and from
      one laboratory-scale plant. The performance of one-step enrichment in Preuss
      tetrathionate broth was better than that of two-step enrichment (buffered peptone
      water pre-enrichment (BPW) and selective enrichment in Rappaport-Vassiliadis (RV)
      medium. The best combinations for Salmonella isolation were xylose-lysine
      deoxycholate (XLD) and Rambach (RB) agars after Preuss enrichment and did not
      differ when brilliant green-magnesium chloride (BM) or brilliant green phenol red
      (BP) agars were used. The two-step enrichment inhibited the growth of both
      salmonellae and interfering accompanying flora. Salmonella-positive plates were
      generally easier to read when inoculated from RV than from Preuss medium because
      of less growth of competing flora. XLD and BM agars supported growth of
      salmonellae and inhibited growth of competing flora better than BP and Rambach
      agars. XLD and BM agars gave the highest numbers of salmonellae isolations but
      XLD and Rambach agars gave the best differentiation. Salmonella levels were < 3-
      > 1100 MPN/100 mL.

PMID- 11464762
TI  - Occurrence of microcystins in raw water sources and treated drinking water of
      Finnish waterworks.
AB  - Problems caused by cyanobacteria are common around the world and also in raw
      water sources of drinking water treatment plants. Strains belonging to genera
      Microcystis, Anabaena and Planktothrix produce potent hepatotoxins, the
      microcystins. Laboratory and pilot scale studies have shown that microcystins
      dissolved in water may pass the conventional surface water treatment processes.
      In 1998 the World Health Organization proposed a guide value of 1 microgram/L for
      microcystin-LR (MC-LR) in drinking water. The purpose of this research was to
      study the occurrence of microcystins in raw water sources of surface waterworks
      and in bank filtration plants and to evaluate the removal of microcystins in
      operating waterworks. Four bank filtration plants and nine surface waterworks
      using different processes for water treatment were monitored. Phytoplankton was
      identified and quantified, and microcystins analysed with sensitive immunoassay.
      Microcystin occurrence in selected water samples was verified with HPLC and a
      protein phosphatase inhibition method. Microcystins were detected sporadically in
      raw water sources of most of the waterworks. In two raw water supplies toxins
      were detected for several months. The highest microcystin concentrations in
      incoming raw water were approximately 10 micrograms/L MC-LR equivalents. In
      treated drinking water microcystins were detected occasionally but the
      concentrations were always below the guide value proposed by WHO.

PMID- 11464763
TI  - Degradation of cyanobacterial hepatotoxins in batch experiments.
AB  - Bank filtration offers a cost effective and low maintenance technique for the
      removal of cyanobacterial hepatotoxins from drinking water. For bank filtration
      to be effective, the toxins must be degraded. The broad aim of this research was
      to determine whether the hepatotoxins, nodularin and microcystin-LR, could be
      completely removed from the soil/water matrix of three soils by microbial
      degradation. The results indicated that complete toxin removal was possible
      within 10-16 d in 2/3 soils that were incubated in the dark at 20 degrees C. The
      soils with the highest organic carbon content (2.9%) and the highest clay content
      (16.1%) were the most effective at removing the toxins in batch experiments.
      However, the sandy soil (98.5% sand) was incapable of degrading either toxin. The
      half-lives of toxin losses due to adsorption, desorption and degradation were
      calculated and for all soils. The degradation process had the highest half-life
      for both toxins. This suggested that degradation was likely to be the rate
      limiting step of complete toxin removal. It was concluded that when a bank
      filtration site was being chosen, the degradation potential and the textural
      properties of the riverbank soil would be important when considering complete
      removal of cyanobacterial hepatotoxins.

PMID- 11464764
TI  - Viral risks associated with wastewater reuse: modeling virus persistence on
      wastewater irrigated salad crops.
AB  - A model for virus decay on lettuce and carrot crops has been derived as part of a
      comprehensive wastewater irrigation microbial risk assessment model under
      development. Results from the decay modeling indicated the presence of a very
      persistent sub-population of viruses evidenced by an initial rapid phase of decay
      followed by a very slow phase. In addition, virus counts fitted a negative
      binomial rather than Poisson distribution indicating over-dispersion. Hence the
      data indicated that viruses were not uniformly distributed over the surfaces of
      both crops. The aim of this paper was to investigate the implications of over
      dispersion and the presence of a very persistent sub-population of viruses for
      assessing viral illness from the consumption of lettuces and carrots irrigated
      with secondary treated effluent. When over-dispersion or clumping of viruses was
      accounted for, a significant increase in the heterogeneity in the risk estimates
      arose. In addition, predicted infection rates were significantly underestimated
      if the presence of a persistent sub-population of viruses was not considered in
      the decay kinetics of the risk model. Hence, both viral clumping and persistence
      sub-populations should be accounted for in future risk assessments of enteric
      viruses associated with wastewater reuse.

PMID- 11464765
TI  - Community surveys of self-reported diarrhoea can dramatically overestimate the
      size of outbreaks of waterborne cryptosporidiosis.
AB  - This paper describes a community-based study undertaken to assess the size of a
      waterborne outbreak of cryptosporidiosis in the North West region of England. The
      outbreak was linked to a single reservoir in the English Lake District and
      provided drinking water to over 1.2 million people. There were some 308
      laboratory confirmed cases. We conducted a community-based survey for self
      reported diarrhoea in four towns within the outbreak area and four control towns.
      The rate of self-reported diarrhoea was higher in the control towns than in the
      outbreak towns. It would appear that retrospective community-based studies of
      diarrhoeal disease are subject to recall bias that would overestimate the
      incidence of illness, especially following reporting in the media. In the light
      of our findings, we reviewed the study undertaken during the Milwaukee outbreak
      that produced the estimated size of 405,000 cases. It is suggested that the
      estimate of the size of the Milwaukee outbreak is severely flawed, and the actual
      size of this outbreak was between 1% and 10% of that claimed.

PMID- 11464766
TI  - HACCP (Hazard Analysis and Critical Control Points) to guarantee safe water reuse
      and drinking water production--a case study.
AB  - To obtain a sustainable water catchment in the dune area of the Flemish west
      coast, the integration of treated domestic wastewater in the existing potable
      water production process is planned. The hygienic hazards associated with the
      introduction of treated domestic wastewater into the water cycle are well
      recognised. Therefore, the concept of HACCP (Hazard Analysis and Critical Control
      Points) was used to guarantee hygienically safe drinking water production. Taking
      into account the literature data on the removal efficiencies of the proposed
      advanced treatment steps with regard to enteric viruses and protozoa and after
      setting high quality limits based on the recent progress in quantitative risk
      assessment, the critical control points (CCPs) and points of attention (POAs)
      were identified. Based on the HACCP analysis a specific monitoring strategy was
      developed which focused on the control of these CCPs and POAs.

PMID- 11464767
TI  - A new analytical tool to assess health risks associated with the virological
      quality of drinking water (EMIRA study).
AB  - This work assessed the risks associated with the virological quality of tapwater
      using a molecular analytical tool manageable in a field survey. It combined a
      daily epidemiological follow-up of digestive morbidity among a panel of
      volunteers and a microbiological surveillance of drinking water. RT-PCR was used
      for detection of enterovirus, rotavirus and astrovirus. 712 cases of acute
      digestive conditions occurred in the 544 volunteers. 38% (9/24) raw water and 23%
      (10/44) tap water samples were positive for at least one virus marker with 9/10
      positive tap water samples complying with bacterial criteria. No statistically
      significant association was found between the presence of viral markers and
      observed incidence of digestive morbidity. However, when an outbreak occurred,
      enterovirus and rotavirus RNA was detected in the corresponding stored tap water
      samples. Sequencing of the amplified fragments showed that the rotavirus detected
      was of bovine origin. This work demonstrated that enteric virus markers were
      common in tapwater of the study communities (characterised by a vulnerable raw
      water) despite absence of bacterial indicators. Tangential ultrafiltration
      coupled to RT-PCR allowed a simultaneous and fast detection of the study viruses
      from environmental samples. This process is a promising tool usable for
      virological water surveillance, in as much the corresponding know-how is
      transferred to the field professionals.

PMID- 11464768
TI  - Pseudomonas aeruginosa as an indicator of health risk in water for human
      consumption.
AB  - During an outbreak of gastroenteritis in 28 children living in a small
      neighbourhood of Cuernavaca city (Mexico), a survey was performed to evaluate the
      confidence in coliform bacteria as sole indicators of potability of drinking
      waters. A primary infection by E. coli and a secondary by Pseudomonas aeruginosa
      was diagnosed in five of the children and the drinking water provided by a well
      was suspected as a transmission source. General and household distribution
      systems, household filters and bottled waters were evaluated for total and faecal
      coliforms, family Enterobacteriaceae, P aeruginosa and residual chlorine. In
      every sample, pathogenic/opportunistic bacteria were isolated even in the absence
      of coliforms and in the presence of residual chlorine. Arbitrarily assigned
      "pollution/risk levels" indicated that the most elevated risk was most frequently
      associated with storage in tanks and with bacterial colonisation in the pipeline
      system and commercial household filters where high levels of P aeruginosa were
      determined. A probability of correspondence between the presence of this
      bacterium and the secondary gastrointestinal infection diagnosed was found
      pointing towards a need for the inclusion of other microorganisms, one of which
      may be P aeruginosa, as indicators of health risk associated with drinking waters
      in Mexico.

PMID- 11464769
TI  - Infectious risk associated with wastewater reuse: an epidemiological approach
      applied to the case of Clermont-Ferrand, France.
AB  - Wastewater reuse raises the question of health risk and the epidemiological
      surveys needed. An epidemiological and environmental approach was used to check
      the security for the exposed populations (surrounding and agricultural population
      in Clermont-Ferrand. Four information systems were set up: two sentinel systems
      joining general physicians (15) and pharmacists (7) for the surrounding
      population and two follow-up surveys among field workers and farmers. Water
      quality monitoring and a study of aerosols from spray irrigation were performed.
      No epidemic event was identified with only some case clusters (not related to
      water exposure) being observed. All the declared cases were benign. The workers'
      survey underlined a substantial incidence of nettle rashes, itchy skins,
      sunburns, and cuts. The follow-up study among farmers and their families did not
      reveal any particular phenomena. The bacteriological quality of treated
      wastewater throughout conformed with the recommendations of the Superior Council
      of Public Health of France (1,000 faecal coliforms/100 mL). No faecal bacteria
      were observed in aerosols with water concentrations equal to 10(3) cfu/100 mL and
      an exposure time of 20 min. The survey of such an irrigation system, towards
      potential and actual risks, required the conjunction of different epidemiological
      information sources and microbiological data.

PMID- 11464770
TI  - Human enteric viruses in Coquina clams associated with a large hepatitis A
      outbreak.
AB  - An outbreak of hepatitis A, affecting 183 people, occurred in Valencia (Spain).
      Epidemiological evidence pointed to an association of the outbreak with
      consumption of Coquina clams (Donax sp), imported frozen from Peru. Shellfish
      were analysed for the presence of hepatitis A virus (HAV), enteroviruses,
      rotaviruses, astroviruses, caliciviruses and hepatitis E virus. HAV was detected
      in 75% of assayed shellfish samples. Other enteric viruses were occasionally
      found in the same samples. Molecular epidemiological analysis of fragments of the
      VP1/2A and the 5' end of the genome from shellfish and sera isolates, revealed
      the presence of six variants belonging to a single genotype.

PMID- 11464771
TI  - Waterborne epidemics in Finland in 1998-1999.
AB  - Fourteen waterborne epidemics occurred in Finland during 1998-1999. About 7,300
      illness cases were registered in these outbreaks. All except one of the
      waterborne epidemics were associated with undisinfected groundwaters. An equal
      number of waterborne epidemics occurred in public and private water systems, but
      most cases of illness occurred in public water systems. The three largest
      epidemics comprised 6,700 illness cases. Insufficient purification treatment
      unable to remove Norwalk-like viruses caused the only waterborne epidemic in a
      surface water plant. The main reasons for groundwater outbreaks were floods and
      surface runoffs which contaminated water. Norwalk-like viruses caused eight and
      Campylobacter three of the outbreaks. In two cases the epidemic ceased by the
      exhaustion of susceptible persons in the exposed community but in most cases it
      was terminated by changing the water source, boiling the drinking water, and
      starting chlorination.

PMID- 11464772
TI  - Astrovirus detection in wastewater samples.
AB  - Procedures for the detection of astroviruses in wastewater samples have been
      developed and evaluated. Following these methodologies, we investigated the
      occurrence of astroviruses in wastewater samples from three different sewage
      treatments plants located in Southern France and two in the Barcelona area. Some
      positive samples were genotyped by analysis of a fragment of the ORF1a by
      restriction fragment length polymorphism (RFLP) with endonuclease DdeI. The
      amplimers generated contain several sites for the DdeI restriction endonuclease,
      being the number and location of sites different between strains.

PMID- 11464773
TI  - Use of rapid enzymatic assays to study the distribution of faecal coliforms in
      the Seine river (France).
AB  - In 1997 and 1998 faecal contamination of the Seine river and its estuary was
      studied for the first time by rapid enzymatic methods, based on the presence of
      the beta-D-glucuronidase enzyme in E. coli, in parallel with traditional plate
      counts of faecal coliforms on specific culture medium. Our study focused on a 450
      km stretch of the river, including the Parisian area, and presenting highly
      variable levels of faecal pollution. Both methods showed that wastewater outfalls
      of the Parisian area and the presence of a maximum turbidity zone (at the mouth
      of the estuary) had a strong impact on the abundance of faecal coliforms in the
      river. Downstream from the Parisian outfalls, beta-D-glucuronidase activity
      measurements decreased 5-6x less rapidly than plate counts suggesting that rapid
      enzymatic assays could detect enzymatically-active but non-culturable bacteria.

PMID- 11464774
TI  - Tirane, Albania: survey on drinking water quality and facilities.
AB  - To develop a realistic model of the situation, a study was carried out in four
      different socioeconomic and hygienic areas of Tirane, namely in the modern and
      historical centre as well as in the intermediate and peripheral areas. In each
      area interviewers from the city's Public Health Directorate, contacted randomly,
      door-to-door, the residents, submitting a questionnaire and collecting water
      samples at the same time. Our data show relevant differences regarding
      distribution and quality of drinking water between the centre and peripheral
      areas. One third of water samples revealed the presence of microorganisms,
      whereas one fifth had no residual chlorine. Altogether more than 200,000 people
      in the peripheral areas of Tirane live under low level hygienic conditions. The
      recent outbreaks of cholera, poliomyelitis and the hyperendemic hepatitis A
      disease are the dramatic results of the low quality drinking water.

PMID- 11464775
TI  - Occurrence of Cryptosporidium oocysts and Giardia cysts in a conventional water
      purification plant.
AB  - A one-year monitoring of Cryptosporidium oocysts and Giardia cysts was conducted
      at a water purification plant. A total of thirteen 50 L samples of river source
      water and twenty-six 2,000 L samples of filtered water (treated by coagulation
      flocculation, sedimentation and rapid filtration) were concentrated using a
      hollow fibre ultrafiltration membrane module at a purification plant.
      Cryptosporidium oocysts were detected in all raw water samples with a geometric
      mean concentration of 400 oocysts/m3 (range 160-1,500 oocysts/m3). Giardia cysts
      were detected in 12/13 raw waters (92%) with a geometric mean concentration of
      170 cysts/m3 (range 40-580 oocysts/m3). Probability distributions of both
      Cryptosporidium oocysts and Giardia cyst concentration in raw water were nearly
      log-normal. In filtered water samples, Cryptosporidium oocysts were detected in
      9/26 samples (35%) with a geometric mean concentration of 1.2 oocysts/m3 (range
      0.5-8 oocysts/m3) and Giardia cysts in three samples (12%) with 0.8 cysts/m3
      (range 0.5-2 oocysts/m3). The estimated removal of Cryptosporidium oocysts and
      Giardia cysts was, respectively, 2.54 log 10 and 2.53 log10 on the basis of
      geometric means, 3.20 and 3.57 log10 on the basis of 50% observation level and
      2.70 and 2.90 log10 on the basis of 90% observation level.

PMID- 11464776
TI  - Setting microbiological water quality standards for sea bathing--a critical
      evaluation.
AB  - The World Health Organization (WHO) recently produced draft guidelines for safe
      recreational water environments. The microbiological standards proposed in the
      guidelines are expected to overestimate the degree of water quality required to
      provide given levels of public health protection. The WHO standards were obtained
      by means of a risk assessment which featured a dose-response model derived from a
      series of randomised controlled trials. The trials have many strengths but biases
      and problems with statistical analysis are likely to have led to over-estimation
      of the risks from bathing in the dose-response model. In addition, the WHO risk
      assessment failed to consider the effects of uncertainty and variability in risk
      estimates and sensitivity to model assumptions. Improved standards could be
      obtained by extending the risk assessment to examine these effects and by
      incorporating a suitably revised dose-response model.

PMID- 11464777
TI  - Helicobacter pylori in water systems for human use in Mexico City.
AB  - Helicobacter pylori infection is associated with peptic ulcers and gastric cancer
      in humans. Transmission of H. pylori is still not certain with some
      epidemiological data suggesting water as a possible transmission route. The
      objective of this study was to detect H. pylori 16S rRNA gene in five water
      systems in the Mexico City area. Samples were taken between 1997 and 2000 from
      extraction wells (system 1), from dams used as water sources, both pre- and post
      treatment (systems 2 and 3), treated wastewater (system 4) and non-treated
      wastewater (system 5). Detection of the H. pylori 16S rRNA gene in water samples
      was carried out using nested PCR in 139 water samples and confirmed by using cagA
      gene detection by PCR-hybridisation. The results showed the presence of H. pylori
      in 58 (42%) of the water samples in total with a prevalence of 68% in system 1,
      100% in system 2, 0% in system 3, 17% in system 4 and 20% in system 5. This first
      stage showed the presence of H. pylori in the tested water systems; nevertheless,
      viability of the microorganism in water and vegetables needs to be confirmed as
      well as demonstration of a relationship between human and environmental strains.

PMID- 11464778
TI  - Occurrence of Legionella in groundwater: an ecological study.
AB  - The natural habitat of Legionella is the water environment. Little is known about
      their presence in groundwater in spite of the fact that many millions around the
      globe regularly rely on groundwaters. This pilot study was aimed at evaluating
      the occurrence of Legionella in groundwater samples (water and biofilms)
      collected from various sites. Water and biofilm samples from selected groundwater
      sources were examined for Legionella using culture media (selective and non
      selective) and a semi-nested PCR assay. Innovative approaches such as
      immunomagnetic separation (IMS) in combination with cultivation and flow
      cytometry were also evaluated. The findings available thus far show that (a)
      Legionella could be readily recovered from groundwater samples by cultivation
      even though their numbers showed considerable variations, (b) surprisingly, the
      PCR methodology was not yet as sensitive as cultivation and (c) flow cytometry
      was not directly applicable on natural samples because of debris and the high
      number of heterotrophic associated microflora from which some members were likely
      to cross-react with the monoclonal antibody used for separation procedures (IMS).

PMID- 11464779
TI  - Workforce planning. What does it all add up to?

PMID- 11464780
TI  - Management costs. Cut and run.
AB  - Government claims that the NHS will have saved 1 bn Pounds on management costs by
      the end of this financial year are exaggerated. Published figures on savings
      since 1997-98 vary considerably. The question of what level of management costs
      the NHS should be expected to bear to run efficiently needs to be addressed.

PMID- 11464781
TI  - Medicines. Peace in a POD (patients' own drug).

PMID- 11464782
TI  - Corporate image. Vision or nightmare?

PMID- 11464783
TI  - Training. Scene setting.

PMID- 11464784
TI  - Primary care. Howling in the wilderness.

PMID- 11464785
TI  - Recruitment. How things work.

PMID- 11464786
TI  - Childcare. Keeping mum.

PMID- 11464787
TI  - Violence. Assault discourse.

PMID- 11464788
TI  - Toxicity and nicotinic acetylcholine receptor interaction of imidacloprid and its
      metabolites in Apis mellifera (Hymenoptera: Apidae).
AB  - Acute oral and contact toxicity tests of imidacloprid, an insecticide acting
      agonistically on nicotinic acetylcholine receptors (nAChR), to adult honeybees,
      Apis mellifera L var carnica, were carried out by seven different European
      research facilities. Results indicated that the 48-h oral LD50 of imidacloprid is
      between 41 and > 81 ng per bee, and the contact LD50 between 49 and 102 ng per
      bee. The ingested amount of imidacloprid-containing sucrose solution decreased
      with increasing imidacloprid concentrations and may be attributed to dose-related
      sub-lethal intoxication symptoms or to antifeedant responses. Some previously
      reported imidacloprid metabolites occurring at low levels in planta after seed
      dressing, i.e. olefine-, 5-OH- and 4,5-OH-imidacloprid, showed lower oral LD50
      values (> 36, > 49 and 159 ng per bee, respectively) compared with the
      concurrently tested parent molecule (41 ng per bee). The urea metabolite and 6
      chloronicotinic acid (6-CNA) exhibited LD50 values of > 99,500 and > 121,500 ng
      per bee, respectively. The pharmacological profile of the [3H]imidacloprid
      binding site in honeybee head membrane preparations is consistent with that
      anticipated for a nAChR. IC50 values for the displacement of [3H]imidacloprid by
      several metabolites such as olefine, 5-OH-, 4,5-OH-imidacloprid, urea and 6-CNA
      were 0.45, 24, 6600, > 100,000, and > 100,000 nM, respectively. Displacement of
      [3H]imidacloprid by imidacloprid revealed an IC50 value of 2.9 nM, thus
      correlating well with the observed acute oral toxicity of the compounds in
      honeybees. Neurons isolated from the antennal lobe of A mellifera and subjected
      to whole-cell voltage clamp electrophysiology responded to the application of 100
      microM acetylcholine with a fast inward current of between 30 and 1600 pA at -70
      mV clamp potential. Imidacloprid and two of the metabolites (olefine- and 5-OH
      imidacloprid) acted agonistically on these neurons, whereas the others did not
      induce currents at test concentrations up to 3 mM. The electrophysiological data
      revealed Hill coefficients of approximately 1, indicating a single binding site
      responsible for an activation of the receptor and no direct cooperativity or
      allosteric interaction with a second binding site.

PMID- 11464789
TI  - Resistance to ACCase-inhibiting herbicides and isoproturon in UK populations of
      Lolium multiflorum: mechanisms of resistance and implications for control.
AB  - Herbicide-resistant Lolium multiflorum (Italian rye-grass) was first reported in
      the UK in 1993 and had been confirmed on 25 farms by 1999. In this study,
      resistance to five herbicides belonging to the aryloxyphenoxypropionate,
      cyclohexanedione and phenyl-urea classes was determined in six populations of L
      multiflorum from the UK under glasshouse and simulated field conditions.
      Glasshouse conditions tended to exaggerate the degree of resistance, but
      experiments performed in both environments detected resistance in four
      populations of L multiflorum. Four populations (Essex A1, Lincs A1, Wilts B1,
      Yorks A2) were resistant to diclofop-methyl, fluazifop-P-butyl, tralkoxydim and
      partially resistant to isoproturon, but only the population from Yorkshire (Yorks
      A2) showed resistance to cycloxydim. Biochemical analyses of acetyl coenzyme A
      carboxylase (ACCase) activity, oxygen consumption by thylakoids, diclofop
      metabolism and glutathione S-transferase activity showed that, in three of the
      resistant populations, an enhanced rate of herbicide metabolism conferred
      resistance. This is the first report world-wide of an enhanced metabolism
      mechanism of diclofop resistance in L multiflorum. In the Yorks A2 population, an
      insensitive ACCase was detected (target-site resistance) which also conferred
      cross-resistance to all of the other ACCase inhibitors investigated.

PMID- 11464790
TI  - Persistence and metabolism of imidacloprid in different soils of West Bengal.
AB  - A laboratory experiment was performed to study the persistence of imidacloprid
      from two formulations (Confidor 200 g litre-1 SL and Gaucho 700 g kg-1 WS), and
      its metabolism in three different soils (Gangetic alluvial soil of Kalyani,
      lateritic soil of Jhargram and coastal alkaline soil of Canning) of West Bengal
      following application at 0.5 kg and 1.0 kg AIha-1. Dissipation of imidacloprid in
      soil followed first-order kinetics and DT50 values ranged from 28.7 to 47.8 days.
      The shortest half-lives (28.7 and 35.8 days) were observed in the lateritic soil
      of Jhargram for both liquid and powder formulations. The formation of two
      metabolites of imidacloprid, imidacloprid-urea and imidacloprid-olefin, was first
      detected on day 30 of degradation at 28 (+/- 1) degrees C in all three soils.

PMID- 11464791
TI  - Toxicity of synthetic piperonyl compounds to leaf-cutting ants and their
      symbiotic fungus.
AB  - The development of Leucoagaricus gongylophorus, the fungus cultured by the leaf
      cutting ant Atta sexdens was inhibited in vitro by synthetic compounds containing
      the piperonyl group. In addition, worker ants that were fed daily on an
      artificial diet to which these compounds were added had a higher mortality rate
      than the controls. The inhibition of the fungal growth increased with the size of
      the carbon side chain ranging from C1 through C8 and decreasing thereafter. 1
      (3,4-Methylenedioxybenzyloxy)octane (compound 5) was the most active compound and
      inhibited the fungal development by 80% at a concentration of 15 micrograms ml-1.
      With worker ants the toxic effects started with compound 5 and increased with the
      number of carbons in the side chain. Thus, for the same concentration (100
      micrograms ml-1) the mortality rates observed after 8 days of diet ingestion were
      82%, 66% and 42%, for 1-(3,4-methylenedioxybenzyloxy)decane, 1-(3,4
      methylenedioxybenzyloxy)dodecane and compound 5, respectively, whereas with
      commercial piperonyl butoxide the mortality was 68%. The latter compound, which
      is known as a synergist insecticide, was as inhibitory to the symbiotic fungus as
      the synthetic compound 5. The possibility of controlling these insects in the
      future using compounds that can target simultaneously both organisms is
      discussed.

PMID- 11464792
TI  - Dicofol resistance in Tetranychus cinnabarinus: resistance and stability of
      resistance in populations from Antalya, Turkey.
AB  - Resistance against dicofol was investigated in the carmine spider mite,
      Tetranychus cinnabarinus. Higher resistance levels were detected by leaf residual
      bioassays than by topical bioassays, both done using a Potter spray tower, in
      almost all populations of T cinnabarinus examined from Antalya, Turkey. For
      instance, the resistance level at LC95 was 17.5-fold in topical bioassays but
      58.9-fold in leaf residual bioassays for the population collected from
      greenhouses in the Topcular district. There were differences of resistance levels
      at LC95, ranging between 2.6- and 23.9-fold using topical bioassays and between
      5.0- and 58.9-fold in residual bioassays, in populations collected from
      greenhouses from various districts. Populations from cotton showed lower
      resistance levels against dicofol than populations from greenhouses. Resistance
      to dicofol at LC50 as indicated by topical and residual bioassays increased 19.7-
      and 100.7-fold, respectively, in a colony from the laboratory strain of T
      cinnabarinus selected with dicofol alone for 16 cycles. However, the dicofol
      resistance at LC50 increased 19.4- and 52.0-fold in another colony selected in
      rotation with dicofol and tetradifon for six and eight cycles, respectively. The
      changes in resistance to dicofol 5 months after the selection ceased were as
      follows: in the colony selected for dicofol alone, using topical and residual
      bioassays, the resistance levels at LC50 decreased to 11.7- and 99.1-fold,
      respectively, and in the colony selected in rotation with dicofol and tetradifon
      to 10.8- and 15.8-fold, respectively.

PMID- 11464793
TI  - Palatability of bird repellents to Rattus norvegicus.
AB  - The palatability to captive, mostly laboratory-bred, Norway rats (Rattus
      norvegicus) of cereal-based baits containing 0.02 g kg-1 brodifacoum, with and
      without bird-repellent additives, was compared in a no-choice experimental
      design. Methyl anthranilate (25 g kg-1), dimethyl anthranilate (25 g kg-1) and
      cinnamamide (2.5 g kg-1) reduced bait consumption by the rats, but all except one
      rat ate enough bait to receive a lethal dose. Cinnamamide (1 g kg-1), ortho
      aminoacetophenone (0.1 g kg-1) and tannic acid (20 g kg-1) did not reduce bait
      consumption and all rats died after eating baits. The concentration of
      cinnamamide palatable to rats has only a low and short-lived repellency to birds,
      so it does not warrant further investigation. However, ortho-aminoacetophenone
      and tannic acid should now be field-tested for palatability to all three rat
      species in New Zealand and for repellency to native New Zealand birds.

PMID- 11464794
TI  - The concentration of pesticides in sediments from Kolleru Lake in India.
AB  - Kolleru Lake is the largest natural freshwater lake in India. Sediment samples
      were collected at different locations from Kolleru Lake at different seasons in a
      year over a period of three years and analyzed for eight selected pesticides. In
      general, pesticides were present at all locations. The selected pesticides alpha
      BHC, gamma-BHC, malathion, chlorpyrifos and endosulfan were present at higher
      concentrations than isodrin, dieldrin and p,p'-DDT. The concentrations of alpha
      BHC, gamma-BHC malathion, chlorpyrifos, isodrin, endosulfan, dieldrin and p,p'
      DDT in sediments were 1.2-388, 1.4-212, from below the minimum detection limit
      (BDL)-186, 1.1-292, BDL-38.6, BDL-206, BDL-128 and BDL-191 micrograms kg-1 dry
      weight, respectively. The aim of this study is to evaluate baseline data, to try
      to account for the concentration of pesticides in sediments and to discuss their
      potential to affect human beings and aquatic organisms.

PMID- 11464795
TI  - Synthesis and in vitro antifungal activity of 1-amino-3,4-dialkylnaphthalene-2
      carbonitriles and their analogues.
AB  - Twenty-four 3- and/or 4-alkyl-substituted 1-aminonaphthalene-2-carbonitriles and
      their analogues were prepared and evaluated for growth-inhibiting activity
      against four phytopathogenic fungi: Fusarium culmorum, Alternaria brassicicola,
      Botrytis cinerea and Penicillium expansum. The results obtained were compared
      with the activity of a commercial fungicide. The highest fungistatic activity was
      revealed by amino nitriles having hydrogen atoms or only one short alkyl group
      (CH3, C2H5) at the 3- or 4-position of the naphthalene system. The minimum values
      of calculated EC50 and EC95 indexes were 1.1 and 5.1 mg litre-1, respectively.
      These values were considerably lower than those for the reference fungicide.

PMID- 11464796
TI  - Adsorption-desorption behaviour of flufenacet in five different soils of India.
AB  - Adsorption-desorption of the herbicide flufenacet (FOE 5043) has been studied in
      five soils from different locations in India (Delhi, Ranchi, Nagpur, Kerala and
      Assam) varying in their physicochemical properties. The organic matter (OM)
      content varied from 0.072 to 0.864%, clay content from 2.5 to 43.7% and pH from
      4.45 to 8.35. The adsorption studies were carried out using a batch equilibration
      technique. Ten grams of soil were equilibrated with 20 ml of aqueous 0.01 M CaCl2
      solution containing different concentrations (0-30 mg litre-1) of flufenacet.
      After equilibration, an aliquot of supernatant was taken out for analysis. During
      desorption, the amount withdrawn for analysis was replenished with fresh 0.01 M
      CaCl2 solution and further equilibrated. Desorption studies were carried out with
      the 30 mg litre-1 concentration of flufenacet only. The adsorption studies
      revealed that there was moderate to high adsorption of flufenacet considering the
      comparatively low organic carbon content in the five test soils. Average Kd
      values ranged from 0.77 to 4.52 and Freundlich KF values from 0.76 to 4.39. The
      highest adsorption was observed in Kerala soil (OM 0.786%; clay 25%; pH 4.45)
      followed by Ranchi, Nagpur and Delhi soils, and the lowest in Assam soil (OM
      0.553%; clay 2.5%; pH 6.87). The trend in adsorption could be attributed to the
      chemical nature of flufenacet and the physicochemical properties of the soil such
      as pH, OM and clay contents. OM and clay contents were positively correlated
      whereas pH was negatively correlated. Soils having low pH, high OM and high clay
      contents showed higher adsorption. Desorption studies revealed that there was a
      hysteresis effect in all the soils. Hysteresis coefficient values (ratio of n(ad)
      and n(des)) varied from 0.09 to 0.45. The study implies that, because of its
      moderate to high adsorption, flufenacet is likely to persist in soil for some
      time. However, the possibility of its movement by leaching or surface run off is
      less.

PMID- 11464797
TI  - The effect of the herbicide diuron on soil microbial activity.
AB  - The inhibitory effect of the herbicide diuron [3-(3,4-dichlorophenyl)-1,1
      dimethylurea] on microbial activity in red Latosol soil was followed using
      microcalorimetry. The activity of the micro-organisms in 1.50 g of soil sample
      was stimulated by addition of 6.0 mg of glucose and 6.0 mg of ammonium sulfate
      under 35% controlled humidity at 298.15 (+/- 0.02) K. This activity was
      determined by power-time curves that were recorded for increasing amounts of
      diuron, varying from zero to 333.33 micrograms g-1 soil. An increase in the
      amount of diuron in soil caused a decrease of the original thermal effect, to
      reach a null value above 333.33 micrograms g-1 of herbicide. The power-time curve
      showed that the lag-phase period and peak time increased with added herbicide.
      The decrease of the thermal effect evolved by micro-organisms and the increase of
      the lag-phase period are associated with the death of microbial populations
      caused by diuron, which strongly affects soil microbial communities.

PMID- 11464798
TI  - Evaluation of endosulfan residues in vegetables grown in greenhouses.
AB  - The reduction in residue levels of endosulfan with time after treatment of
      tomatoes, green beans, peppers and cucumbers grown in different types of
      commercial greenhouses (flat- and asymmetric-roof greenhouses) in Almeria (Spain)
      was investigated. A study of the major and minor degradation products of
      endosulfan in peppers and cucumbers (endosulfan-sulfate, -ether and -lactone) was
      carried out using gas chromatography-tandem mass spectrometry (GC-MS/MS). To
      establish the influence of environmental conditions on the degradation of
      endosulfan, several field trials have been carried out in which crops were
      sprayed at different rates (full, half- and quarter- of those rates recommended)
      during two seasons (spring and winter). For statistical purposes, the
      disappearance of endosulfan with time was considered to follow a pseudo-first
      order reaction. Analysis of variance (ANOVA) has been applied to the results
      obtained. Half-lives of residue disappearance were 4.03-4.68 days in green beans,
      4.03-4.20 days in tomatoes, 8.22 days in peppers and 7.97 days in cucumbers. Half
      lives in spring were shorter than in the winter season. The application rate and
      the type of greenhouse did not influence the half-lives.

PMID- 11464799
TI  - Common names of pesticides recently approved by the BSI.

PMID- 11464800
TI  - Re: Gulliver G 100--A new device to evaluate daily growth measurement in
      comparison with Harpenden stadiometer. Glock et al.[Horm Res 1999;52:287-290].

PMID- 11464801
TI  - The study of laryngeal muscle activity in normal human subjects and in patients
      with laryngeal dystonia using multiple fine-wire electromyography.
AB  - The normal human larynx performs numerous complex tasks with nearly complete
      reliability. These tasks require precise timing of movements that are effected by
      the laryngeal muscles. The most specific method to examine these muscles is by
      electromyography. Although many studies on laryngeal electromyography have been
      reported using multichannel recordings, none has provided a detailed analysis of
      each laryngeal muscle's role during a variety of common tasks and the spectrum of
      normative values. Simultaneous eight-channel, fine-wire electromyographic
      recordings were made in 11 human subjects. The timing patterns of the laryngeal
      muscles during the coordinated efforts for phonation and other common glottic
      functions were examined. In addition, normative values for latencies and
      amplitudes of response were determined. During simple phonation, a "set pattern"
      for the thyroarytenoid, lateral cricoarytenoid , and interarytenoid muscles was
      found. The thyroarytenoid and lateral cricoarytenoid muscles demonstrated a burst
      at onset preceding phonation and then decreased activity, whereas the
      interarytenoid sustained glottic position during phonation. The coordination of
      the laryngeal muscles was similarly determined for connected speech, respiration,
      Valsalva maneuver, cough, throat-clear task, and swallow. These patterns of
      response, the latencies for activities, and the amplitudes of response in normal
      subjects provided the basis to examine the abnormal laryngeal function in a group
      of 59 patients with four clinical varieties of laryngeal dystonia (adductor,
      tremor, abductor, and mixed). The findings include abnormal patterns of response,
      increased latencies, and increased amplitudes of recruitment in many tasks
      including nonphonatory tasks. Although specific distinctions were noted in each
      group, the responses were remarkably similar, indicating that all clinical
      varieties of laryngeal dystonia should be classified as mixed dystonia with a
      clinical preponderance for one or more types of behavior.

PMID- 11464802
TI  - I. The moral status of the pre-implantation embryo.

PMID- 11464803
TI  - II. The cryopreservation of human embryos.

PMID- 11464804
TI  - ECG of the month. Wide QRS tachycardia.

PMID- 11464805
TI  - The ten most commonly asked questions about stroke prevention in atrial
      fibrillation.

PMID- 11464806
TI  - Obesity is bad: but what should the definition be, and when is it bad?

PMID- 11464807
TI  - Robert Wood Johnson Foundation, IHI launch "Pursuing Perfection" program in
      health care.

PMID- 11464808
TI  - AHRQ chief answers patient safety/research questions.

PMID- 11464809
TI  - Developing cross-national CME for mental disorders in Europe.

PMID- 11464810
TI  - Tardive dyskinesia exacerbating with mania in a bipolar patient.

PMID- 11464811
TI  - Successful treatment with clozapine in a patient with neuroleptic-induced acute
      laryngeal dystonia.

PMID- 11464812
TI  - Improvement in antithrombotic management in atrial fibrillation also requires
      effective INR control.

PMID- 11464813
TI  - Anticoagulation and atrial fibrillation.

PMID- 11464815
TI  - A twenty-first century call for public health workforce development.

PMID- 11464814
TI  - Implementation of antithrombotic management in atrial fibrillation.

PMID- 11464816
TI  - [Chronic lymphatic leukemia. 3. The concrete case].

PMID- 11464817
TI  - Index of suspicion. Case 2. Diagnosis: Ludwig angina.

PMID- 11464818
TI  - Index of suspicion. Case 3. Diagnosis: Acute primary adrenal insufficiency.

PMID- 11464820
TI  - Recommendations for suspended doctors must be enacted.

PMID- 11464819
TI  - Doctors must learn to let others treat them and their families.

PMID- 11464821
TI  - Closing the gap between professional teaching and practice. Applying ethical
      principles is sometimes difficult for students.

PMID- 11464822
TI  - Closing the gap between professional teaching and practice.  Ethical guidance for
      teaching applies to postgraduate education as well.

PMID- 11464823
TI  - Spreading research in primary care safely.

PMID- 11464824
TI  - Consumers are helping to prioritise research.

PMID- 11464825
TI  - Is bigger better for primary care groups and trusts? Small can be beautiful and
      effective.

PMID- 11464826
TI  - Is bigger better for primary care groups and trusts? Culture and leadership are
      also important.

PMID- 11464827
TI  - Is bigger better for primary care groups and trusts? Larger trusts may reduce
      inequalities.

PMID- 11464828
TI  - Elderly people's technique in using dry powder inhalers. New inhaler devices are
      rarely used by older people in the community.

PMID- 11464829
TI  - Elderly people's technique in using dry powder inhalers. Zanamivir and unreason
      seem to go together.

PMID- 11464830
TI  - Diagnosis of acute appendicitis. Appendicitis is a separate clinical entity in
      men and women.

PMID- 11464831
TI  - Cardiovascular events in users of sildenafil. Paper does not provide any
      reassurance.

PMID- 11464832
TI  - Hepatitis B, lamivudine, and HIV.

PMID- 11464833
TI  - Addison's disease should be diagnosed biochemically.

PMID- 11464834
TI  - Fetal growth markers may show nutritionally mediated effect.

PMID- 11464835
TI  - Adult obesity depends on genes and environment.

PMID- 11464836
TI  - Liver cirrhosis is risk factor for pyogenic liver abscesses.

PMID- 11464837
TI  - Responsibilities of sponsors are limited in premature discontinuation of trials.

PMID- 11464838
TI  - Fertility treatment in HIV needs multidisciplinary team.

PMID- 11464839
TI  - Iraqi doctors appeal for help from doctors in other countries.

PMID- 11464840
TI  - Health-related decision limits rather than reference limits to guide the use of
      ferritin measurements.

PMID- 11464842
TI  - Health centres and GP surgeries should provide bicycle parking.

PMID- 11464843
TI  - Setting priorities for science funding.

PMID- 11464844
TI  - Socioeconomic biological weapons.

PMID- 11464845
TI  - First words.

PMID- 11464846
TI  - Effects of lead exposure.

PMID- 11464847
TI  - El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral
      sclerosis.

PMID- 11464848
TI  - Animal models of amyotrophic lateral sclerosis.
AB  - Animal models of human disease are important in unravelling the pathophysiology
      of the condition, for exploring the natural history of disease and for evaluating
      potential therapies. The development of animal models of human neurodegenerative
      disease such as ALS is particularly challenging, given the paucity of knowledge
      of their aetiology and the organizational specificity of the human motor system.
      Nonetheless, a range of spontaneously occurring, experimentally produced, or
      genetically engineered models of ALS are now available. Although not always a
      perfect replica of the ALS disease, these models are shown to be of outstanding
      importance for investigations of the mechanisms of dysfunction/death of motor
      neurons in vivo. This is particularly true for the transgenic mouse models
      expressing superoxide dismutase or cytoskeletal proteins. This approach has
      provided an unparalleled opportunity for testing of potential pharmacological or
      gene therapies, and it can be expected that the results of these studies will be
      translated into the clinical advances of the next years.

PMID- 11464849
TI  - An overview of H-reflex studies in amyotrophic lateral sclerosis.
AB  - H-reflex methods were used to investigate motor neuron excitability and the basic
      physiology of segmental spinal reflexes. While many studies have been performed
      using these electrophysiological techniques, in both normal subjects and patients
      with different neurological diseases, few studies have focused on patients
      affected by amyotrophic lateral sclerosis (ALS). This article reviews the various
      electrophysiological techniques which use H-reflex to study the physiology of
      segmental spinal reflexes in motor neuron diseases. Their possible applications
      for elucidating pathophysiological mechanisms in ALS and for monitoring the
      disease during clinical trials are discussed.

PMID- 11464850
TI  - Cyclin-dependent kinase-5 (CDK5) and amyotrophic lateral sclerosis.
AB  - Cyclin-dependent kinase-5 (CDK5) is a serine-threonine protein kinase that has
      been implicated in a number of physiological processes in nerve and muscle cells,
      including neurogenesis, neuritic outgrowth, axonal transport of membrane-bound
      organelles and myogenesis. CDK5 has also been shown to phosphorylate the
      important cytoskeletal proteins, neurofilament and tau, both in vitro and in
      cells. The latter has prompted study into the potential role of CDK5 in the
      hyperphosphorylation of these proteins as part of the neuropathology seen in
      amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. More
      recently, increasing evidence has suggested a role for CDK5 in cellular
      apoptosis. Apoptosis has been implicated as the final common pathway of cell
      death in a number of neurodegenerative diseases including ALS. This article sets
      out to review the physiological and pathological roles ascribed to CDK5 and the
      possible relevance thereof to the pathogenesis of ALS.

PMID- 11464851
TI  - Improving the quality of life for people with ALS: the challenge ahead.
AB  - In tandem with recent progress in basic and clinical research in amyotrophic
      lateral sclerosis (ALS), clinical care and management has improved substantially.
      Key processes and practices have been established and are specified in current
      ALS Practice Parameters; the international ALS databases identify the current
      status of care and management given by physicians. A number of prospective
      clinical management research studies are now well underway to establish the
      effective utility of enteral feeding, assistive ventilatory device, and exercise
      in patients with ALS. One of the main research objectives in the clinical
      management of ALS is to improve patients' quality of life. For patients with ALS,
      only comprehensive multidisciplinary care can effectively improve their overall
      quality of life from diagnosis to death. This paper will briefly review a number
      of factors that must be considered if we are to improve the quality of life for
      these patients, including comprehensive medical management, patient education,
      the importance of hope, the role of the health care professional, and the
      patients themselves.

PMID- 11464852
TI  - Spiritual well-being of the individual with amyotrophic lateral sclerosis.
AB  - BACKGROUND: A study was conducted to: (1) establish the feasibility and
      reliability of the Spiritual Well-Being Scale (SWBS) and its religious (RWB) and
      existential well-being (EWB) subscales in a sample of individuals with ALS; (2)
      describe the spiritual and religious practices, and spiritual well-being in these
      individuals; and (3) examine the relationship between spiritual well-being and
      quality of life. METHOD: A random sample of 60 individuals completed the SWBS at
      the beginning and end of an ALS clinic visit. Subjects were classified into
      early, middle or late stage of ALS, using vital capacity and total ALS Functional
      Rating Scale scores. A subsample completed the Sickness Impact Profile (SIP).
      RESULTS: The SWBS and its RWB and EWB subscales were found to have high internal
      consistency and test-retest reliability. There were no statistically significant
      differences in SWB, RWB or EWB scores among the three stages of ALS. RWB scores
      were significantly higher than EWB scores overall and within the middle and late
      stages. Strong negative correlations were found between physical and psychosocial
      dimension SIP subscores and RWB scores, suggesting that religious well-being may
      impact quality of life, or vice versa.

PMID- 11464853
TI  - Cognitive function in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      of unknown etiology. Although there was a widely held belief that ALS does not
      cause cognitive impairment, cognitive function in patients with ALS has received
      more attention recently. In this paper, we discuss the clinical, neuroanatomical
      and neuropathological basis for cognitive dysfunction in ALS.

PMID- 11464854
TI  - Amyotrophic lateral sclerosis with multiple sclerosis: a clinical and
      pathological report.
AB  - We report a 62-year-old woman with a past history of painful central visual loss
      who developed progressive quadriparesis and bulbar palsy. Neurological
      examination revealed widespread upper and lower motor neuron signs in the bulbar
      region and extremities. Electromyography demonstrated widespread active and
      chronic motor axon loss. Magnetic resonance neuroimaging studies revealed
      enhancing callosal and periventricular white matter lesions and cervical and
      thoracic cord hyperintensities. Cerebrospinal fluid analysis was consistent with
      multiple sclerosis. The patient died of respiratory failure two years after
      presentation, and autopsy revealed multifocal demyelination involving the corpus
      callosum, cerebellum and spinal cord as well as pathologic findings typical of
      amyotrophic lateral sclerosis. A review of the literature confirms the
      exceedingly unusual combination of amyotrophic lateral sclerosis with multiple
      sclerosis.

PMID- 11464855
TI  - Intratumoural heterogeneity of 1p deletions and MYCN amplification in
      neuroblastomas.
AB  - BACKGROUND: At least three genetic hallmarks identify aggressive tumour behaviour
      in neuroblastomas; amplification of the oncogene MYCN; deletion (loss of
      heterozygosity [LOH]) at the short arm of chromosome 1 (del1p36), seen in
      approximately 28% of the cases; and di-tetraploidy. The MYCN oncogene is
      amplified in approximately 23% of all neuroblastomas and becomes important for
      the stratification of therapy in localised and 4s tumours. Up to now, it has been
      believed that the genetic constellation of neuroblastic tumours is stable and
      does not alter during tumour evolution or during tumour progression. PROCEDURE:
      Using fluorescence in situ hybridisation techniques (FISH) to investigate
      different tumour areas on touch preparations and histological sections, we show
      that genetic heterogeneity can be detected in neuroblastomas, especially in
      tumours detected by urinary mass screening. CONCLUSION: The identification of
      such cell clones is important, because the MYCN amplification and/or the deletion
      at 1p36 appear to be responsible for aggressive local growth and development of
      metastases.

PMID- 11464856
TI  - Stromal cells and human malignant neuroblasts derived from bone marrow metastasis
      may share common karyotypic abnormalities: the case of the IGR-N-91 cell line.
AB  - BACKGROUND: Stage IV neuroblastoma is characterized by tumor invasion and
      metastatic dissemination. Cell lines derived from such neuroblastomas have a high
      in vitro proliferation capacity. PROCEDURE: We established three neuroblastoma
      cell lines derived from involved bone marrow of three patients with stage IV
      neuroblastoma and performed a cytogenetic study. RESULTS: Various culture
      conditions allowed us to distinguish two cell subpopulations: malignant
      neuroblasts (Nb-type) and substrate-adherent stromal cells (Str-type). Karyotypic
      analyses revealed two specific chromosomal abnormalities in diploid malignant IGR
      N-331 neuroblasts, der(1)t(1;7)(p22;q11) and der(5)t(5;17)(q35;q21), one
      unbalanced translocation der(1)t(1;17)(p35;q21)x2 in hyperdiploid malignant IGR-N
      337 neuroblasts, and a normal karyotype in both corresponding stromal
      subpopulations. In contrast, in the IGR-N-91 model, both cell types shared two
      unbalanced translocations, t(1;4)(q12;p15) and t(2;10)(p14;q11), suggesting that
      stromal cells and malignant neuroblasts originate from a common stem cell.
      CONCLUSIONS: Based on our findings, we postulate that genetically modified
      stromal cells may influence the metastatic potential of malignant neuroblasts.

PMID- 11464857
TI  - Retinoblastoma family proteins induce differentiation and regulate B-myb
      expression in neuroblastoma cells.
AB  - BACKGROUND: The expression of several genes is modulated during neuroblastoma
      differentiation. The retinoblastoma family proteins, pRb, p107 and pRb2/p130, act
      in the repression of proliferation genes, interacting mainly with the E2F
      transcription factors. PROCEDURE AND RESULTS: In this study, we found that, in
      neuroblastoma cell lines, pRb and p107 proteins decreased, undergoing progressive
      dephosphorylation, whereas pRb2/p130 increased at late stages of differentiation.
      B-myb expression was down-regulated in association with the up-regulation of
      pRb2/p130, the major partner of E2F on the E2F site of the B-myb promoter in
      differentiated cells. Transfection of each of the retinoblastoma family genes in
      neuroblastoma cells was able to induce neural differentiation, to inhibit 3H
      thymidine incorporation, and to down-regulate B-myb promoter activity.
      CONCLUSIONS: In conclusion, our data suggest a major contribution of
      retinoblastoma proteins, and especially of pRb2/p130, in B-myb promoter
      regulation and demonstrate the induction of neural differentiation by p107 and
      pRb2/p130, suggesting a role of these proteins in triggering differentiation
      specific genes.

PMID- 11464858
TI  - TrkA signal transduction pathways in neuroblastoma.
AB  - BACKGROUND: Favorable neuroblastomas frequently express high levels of the TrkA
      receptor, and these tumors have a propensity to either differentiate or regress,
      but the mechanisms responsible for these two fates are unclear. PROCEDURE: To
      study TrkA signal transduction in neuroblastoma (nb), we stably expressed wild
      type TrkA and five TrkA mutants in the human nb cell line SH-SY5Y. Resulting
      single cell clones were characterized by TrkA mRNA and protein expression and by
      autophosphorylation of the receptor. RESULTS: Introduction of TrkA restored nerve
      growth factor (NGF) responsiveness of SH-SY5Y cells, demonstrated by
      morphological differentiation and induction of immediate-early genes. TrkA
      overexpression leads to growth inhibition in the absence of NGF, whereas NGF
      treatment results in increased proliferation. CONCLUSIONS: Analysis of downstream
      signaling elements in mutated TrkA receptors indicates that NGF-induced
      differentiation is dependent on TrkA kinase activity, but several redundant
      pathways seem to be used farther downstream. This suggests differences from TrkA
      pathways identified in PC12 cells.

PMID- 11464859
TI  - Distal chromosome 17 gains in neuroblastomas detected by comparative genomic
      hybridization (CGH) are associated with a poor clinical outcome.
AB  - PROCEDURE: To establish the significance of chromosome 17 aberrations in the
      biology of neuroblastomas, the fresh-frozen material of 53 primary neuroblastomas
      (average patient age: 20.8 months; stage 1 or 2: n = 10; stage 3: n = 10; stage
      4: n = 10; stage 4s: n = 23) was studied by means of comparative genomic
      hybridization (CGH). Follow-up data were available for 52 of 53 cases studied
      (average follow-up period: 26.4 months). Except for one, all cases had previously
      been analyzed for MYCN status (semiquantitative Southern blot analysis). Studies
      of LOH 1p36 (VNTR-PCR) had been performed on 28 of 53 cases. RESULTS: Chromosome
      17 gains were detected in 46 of 53 (86.8%) cases. Whole chromosome gains were
      mostly restricted to localized tumors (stage 1 or 2: 9 of 10 cases; stage 4s:19
      of 23; stage 3: 2 of 10; stage 4:0 of 10 cases), whereas distal 17 gains were
      significantly associated with clinically advanced tumor stages and patients aged
      over 1 year at diagnosis. Univariate analyses revealed a statistically
      significant correlation of distal 17q gains with overall survival (P< 0.01, MYCN
      amplification: P< 0.01; 1p deletion: P< 0.01) and an elevated recurrency rate
      (17q: P= 0.02, MYCN amplification: P = 0.05; 1p deletion P= 0.3). There was a
      strong coincidence of distal 17q gains and 1p deletion or MYCN amplification (P <
      0.01). CONCLUSION: Our data indicate that distal chromosome 17q gains are of
      major prognostic relevance for neuroblastoma patients. However, studies on a
      larger series of tumors have to be performed to assess whether or not these
      alterations are independent prognostic markers of a poor clinical outcome.

PMID- 11464860
TI  - Expression of Fas (APO-1/CD95) and Fas ligand (FasL) in human neuroblastoma.
AB  - BACKGROUND AND PROCEDURE: To determine the possible role of Fas/FasL system in
      the particularly heterogeneous behaviour of neuroblastoma (NB), we have measured
      the functional expression of Fas and its ligand, FasL, in primary neuroblastoma
      samples and cell lines by immunohistochemistry and flow cytometry. RESULTS: Our
      results reveal that while Fas expression is associated with low stage and more
      mature tumors, heterogeneous FasL expression was mostly detected in high stage
      tumors, with our apparent correlation to MYCN amplification. Flow cytometric
      analysis of cell lines demonstrated a high expression of Fas in epithelial-type,
      HLA class I positive cell lines, which was lost upon activation with phorbol
      esters. In contrast, Fas ligand was detected in only a small subset of cell
      lines. CONCLUSIONS: In some cell lines, cytotoxic assays revealed the ability of
      NB-associated Fas receptor to transduce an apoptotic signal upon triggering. The
      pattern of functional Fas/FasL expression in tumours and cell lines suggests that
      this system may be involved in the evasion of highly malignant neuroblastoma
      cells to host immune response.

PMID- 11464861
TI  - Apoptosis in neuroblastomas induced by interferon-gamma involves the CD95/CD95L
      pathway.
AB  - BACKGROUND AND PROCEDURE: The CD95/CD95 ligand (CD95L) system is a key regulator
      of apoptosis. To evaluate a possible role of the CD95/CD95L system in human
      neuroblastoma (NB) cells, we investigated the constitutive and interferongamma
      (INFgamma)-induced expression of CD95 and CD95L, and CD95-mediated cell death in
      the SK-N-BE(2) cell line. RESULTS: Modulation of CD95/CD95L expression and
      triggering of an autocrine apoptotic mechanism by IFNgamma suggest a potential
      role for INFgamma as a therapeutic agent for NB. CONCLUSIONS: The evidence that
      retinoids induce apoptosis via tissue transglutaminase (tTG) and that N-methyl-D
      aspartate (NMDA) and gp120 act through the nitric oxide synthase (NOS) activation
      pathway, indicates the existence of different molecular mechanisms of action,
      whose pharmacological exploitation might be used in an additive fashion.

PMID- 11464862
TI  - Signaling pathway of ciliary neurotrophic factor in neuroblastoma cell lines.
AB  - BACKGROUND: Ciliary neurotrophic factor (CNTF) is a member of the interleukin-6
      (IL-6) cytokine family and affects the survival and differentiation of several
      classes of neurons. For signal transduction, CNTF requires a receptor complex,
      composed of the IL-6 signal transducing molecule gp130, leukemia inhibitory
      factor receptor (LIFR)-beta, and CNTFR-alpha. There are two major independent
      pathways (Jak-STAT and Ras-MAPK) in cell signaling, and some recent reports show
      interaction between these pathways. The signal of the IL-6 family is mainly
      transduced to the Jak-STAT pathway through gp130. However, it has not been
      examined in neuroblastoma in detail. PROCEDURE AND RESULTS: Here we examine the
      signaling pathway of CNTF in 11 neuroblastoma cell lines. Northern blot analysis
      revealed that 3 of the 11 cell lines expressed c-fos mRNA after CNTF stimulation.
      Cell lysates were immunoprecipitated with agarose-conjugated antiphosphotyrosine
      antibody and blotted with anti-gp130, anti-Jak1, or anti-STAT3 antibody. Tyrosine
      phosphorylation of gp130, Jak1, and STAT3 was observed after CNTF stimulation in
      these three cell lines. Furthermore, tyrosine phosphorylation of ERK1 (one of the
      MAPKs) was also observed in all of them. CONCLUSIONS: These results demonstrate
      that CNTF signaling is conserved in some of the neuroblastoma cell lines and
      suggest that not only a Jak-STAT pathway but a MAPK pathway is activated by CNTF
      through gp130 in neuroblastoma cell lines.

PMID- 11464864
TI  - The vitamin A analogues: 13-cis retinoic acid, 9-cis retinoic acid, and Ro 13
      6307 inhibit neuroblastoma tumour growth in vivo.
AB  - BACKGROUND: Neuroblastoma, a childhood tumour of the sympathetic nervous system,
      may undergo spontaneous differentiation or regression due to apoptosis after no
      or minimal therapy. However, the majority of neuroblastomas are diagnosed as
      metastatic tumours with a poor prognosis in spite of intensive multimodal
      therapy. Vitamin A and its analogues (retinoic acid, RA) play an important role
      in normal cel lular differentiation and programmed cell death. RA regulates
      neuroblastoma growth and differentiation in vitro, and has shown activity against
      human neuroblastoma in vivo. PROCEDURE: Recently, 9-cis RA was shown to induce
      apoptosis in vitro in neuroblastoma using a 5 days short-term treatment and
      subsequent washout. In the present study, nude rats with human neuroblastoma SH
      SY5Y xenografts were treated with 13-cis RA (4 mg po daily), 9-cis RA (5 mg po
      daily) or the novel analogue Ro 13-6307 (0.3 mg po daily) using either a
      continuous or short-term schedule. RESULTS: ALL three different retinoids
      decreased neuroblastoma growth significantly in terms of tumour weight after 8-12
      days when compared to untreated controls (P < 0.05). Minor signs of toxicity in
      13-cis RA treated rats were observed. However, severe toxicity with significant
      weight loss was seen in all rats treated with 9-cis RA and Ro 13-6307. Toxicity
      was more pronounced with the continuous regimen. CONCLUSIONS: We conclude that
      different retinoids reduce neuroblastoma tumour growth in vivo. Drug scheduling
      and dosage may affect both therapeutic efficacy and toxic side effects. Further
      in vivo studies are warranted, including pharmacokinetic and molecular analyses,
      before clinical trials with promising retinoids like 9-cis RA and Ro 13-6307 can
      be started in children with neuroblastoma.

PMID- 11464863
TI  - Retinoic acid-induced apoptosis of the CHP134 neuroblastoma cell line is
      associated with nuclear accumulation of p53 and is rescued by the GDNF/Ret
      signal.
AB  - BACKGROUND: Neuroblastoma (NBL) is one of the most common solid malignancies in
      childhood and is derived from the sympathetic precursor cells. Although p53, a
      tumor suppressor, has been reported to be rarely mutated in NBLs, it is
      sequestered abnormally in the cytoplasm of the NBL cell. The mechanism and
      functional role of the abnormal intracellular localization of p53 remain unclear.
      PROCEDURE: Here, we established an in vitro system of apoptosis model using a NBL
      cell line CHP134 which also showed a cytoplasmic sequestration of p53. The
      treatment of the cells with 1 or 5 microM all-trans retinoic acid (RA) induced
      moderate neurite outgrowth followed by massive death of CHP134 cells by days 5 to
      6. RESULTS: TUNEL staining showed that the cell death was due to apoptosis.
      Immunofluorescent stain demonstrated that p53 was strongly positive in the
      nucleus on day 5, which was accompanied with induction of p21WAF1. In addition,
      expression of caspase-3 was also increased during the cell death. Intriguingly,
      the RA treatment induced expression of Ret tyrosine kinase receptor in CHP134
      cells. CONCLUSIONS: The addition of ligands, glial cell line-derived neurotrophic
      factor (GDNF) and neurturin (NTN), inhibited apoptosis as well as nuclear
      accumulation of p53 in the cell. The present results suggest that the RA-induced
      apoptosis of NBL cells is associated with activation of both the caspase cascade
      and the p53-mediated pathway with its nuclear translocation. The neurotrophic
      signal through the GDNF-Ret system may prevent the neuronal cell death.

PMID- 11464865
TI  - Downregulation of hASH1 is associated with the retinoic acid-induced
      differentiation of human neuroblastoma cell lines.
AB  - BACKGROUND: MASH1, a transcription factor with basic helix-loop-helix domain, has
      a pivotal function to promote differentiation of neural crest cells into
      autonomic neurons. PROCEDURE: To investigate the functional significance of human
      MASH1 (hASH1) in the pathogenesis of neuroblastoma, which is originated from
      autonomic precursor cells, we studied hASH1 gene expression in primary
      neuroblastomas and human nueroblastoma cell lines. RESULTS: The follovving
      results were obtained: (i) hASH1 was expressed in 40 out of 61 (66%) primary
      neuroblastomas, (ii) hASH1 transcripts were downregulated in several cell lines
      prior to differentiation induced by all-trans retinoic acid (RA), (iii) a
      neuroblasotma cell line without expression of endogenous hASH1 did not respond to
      RA at all, and (iv) the analysis of the hASH1 genomic DNA revealed two possible
      transcription initiation sites, which may correspond to 3.0 kb and 3.5 kb
      transcripts. CONCLUSIONS: Our observations suggest that, although hASH1 may not
      preserve the growth capacity of neuroblastomas, downregulation of hASH1 may be
      necessary to promote neuronal differentiation of neuroblastoma.

PMID- 11464866
TI  - Differential gene regulation by 9-cis and all-trans retinoic acid in
      neuroblastoma cells.
AB  - BACKGROUND: 9-cis retinoic acid (RA) is more effective than all-trans RA at
      inducing neuroblastoma differentiation in vitro, and has distinct biological
      properties with respect to its ability to promote apoptosis in N-type
      neuroblastoma cells. The cellular effects of 9-cis RA may, in part, result from
      activation of retinoid X receptor (RXR) homodimers. If this hypothesis is
      correct, 9-cis RA may control the expression of a different subset of retinoid
      regulated genes compared to all-trans RA. PROCEDURE: We have therefore used
      differential mRNA display to identify genes differentially expressed in
      neuroblastoma cells in response to all-trans and 9-cis RA. RESULTS: The majority
      of cDNAs differentially expressed in response to all-trans or 9-cis RA matched to
      nonredundant Genbank sequences or EST database sequences. Differential-display
      profiles were similar in SH SY 5Y and SH S EP cells, clonal derivatives of the
      mixed neuroblastoma cell line SK N SH, although there were apparent differences
      between these cell lines with respect to the retinoid-regulation of specific RT
      PCR cDNA fragments. CONCLUSIONS: These data support the view that 9-cis and all
      trans RA act via different receptor mechanisms.

PMID- 11464867
TI  - Role of CD44H carbohydrate structure in neuroblastoma adhesive properties.
AB  - BACKGROUND: CD44 represents a heterogeneous group of surface glycoproteins
      involved in cell-cell and cell-matrix interactions. CD44H is the major receptor
      for hyaluronate, and most if not all CD44H known functions are attributed to its
      ability to recognize hyaluronate. We have previously demonstrated a lack of CD44
      expression in high stages and NMYC-amplified tumors and further have shown that
      NMYC-amplified cell lines either did not express CD44 at all or expressed a
      nonfunctional receptor. On the other hand, nonamplified cells constitutively
      expressed an active receptor, suggesting that absence of CD44-mediated hy
      aluronate binding could be related to increased malignancy in human
      neuroblastoma. PROCEDURE: In the present study we have compared the glycosylated
      structure of CD44 expressed by NMYC amplified vs. nonamplified cell lines in
      relation to their adhesive properties for hyaluronate. These adhesive properties
      were measured after modifications of the carbohydrate structure with enzymes and
      inhibitors of N- or O-linked glycosylation. RESULTS AND CONCLUSIONS: Our results
      indicate that increased sialylation, defective N-linked glycosylation, and
      substitution of the CD44 glycoprotein with keratan sulfate glycosaminoglycan
      might include modifications observed on neuroblastoma cells that could account
      for the inability of the receptor to bind hyaluronate.

PMID- 11464868
TI  - 17q gain in neuroblastoma predicts adverse clinical outcome. U.K. Cancer
      Cytogenetics Group and the U.K. Children's Cancer Study Group.
AB  - BACKGROUND: It is now recognized that gain of chromosome 17 material is the most
      frequent genetic abnormality of neuroblastoma cells. Several studies have linked
      17q gain with known adverse prognostic factors: patient age >1 year, advanced
      stage disease, deletion of chromosome arm 1 p, and amplification of the MYCN
      oncogene. We sought to further investigate the clinical and prognostic
      associations of chromosome 17 status in relation to other well-established
      predictive factors. PROCEDURE: In a collaborative study by UK cytogenetics
      centres, we compiled a series of 104 neuroblastoma tumours for which the status
      of chromosome 17 was confidently defined by cytogenetics, metaphase or interphase
      FISH, or CGH analysis. The results were correlated with data on 1p and MYCN, and
      with centrally collated clinical and survival information. RESULTS: Gain of 17q
      (i.e., unbalanced gain of segment 17q21-qter) was found in 66.3% of tumours,
      while 33.7% showed a '17q normal' status (i.e., no gain at all, or gain of whole
      chromosome 17 relative to ploidy). Gain of 17q was strongly associated with
      advanced stage disease, patient age >1 year, 1p deletion, and MYCN amplification
      (all P< 0.01). In univariate analysis, 17q gain was a significant predictor of
      adverse outcome (projected 5 year relapse-free survival 15.6% compared to 75.2%
      in cases lacking this feature in tumour cells; (P < 0.0001). In multivariate
      analysis, 17q gain was more strongly associated with adverse outcome than was
      either stage (Stage 4 vs other combined) or 1p status. CONCLUSION: We conclude
      that gain of chromosome segment 17q21-qter is of great biological and clinical
      importance in neuroblastoma, and that its detection at diagnosis should be a
      priority.

PMID- 11464870
TI  - Distribution of natural antibody against human neuroblastoma among children with
      or without neuroblastoma.
AB  - BACKGROUND: This study was conducted to examine the distribution of a natural
      antibody against neuroblastoma (NB) among Japanese children and to clarify the
      clinical significance of the presence of this antibody in the sera during
      treatment in patients with International Neuroblastoma Staging System Stage 4 NB.
      PROCEDURE: Human sera were obtained from 8 healthy volunteers, 82 patients with
      non-malignant surgical diseases, and 35 patients with NB including 3 with Stage 1
      disease, 6 with Stage 2, 7 with Stage 3, 17 with Stage 4, and 2 with Stage 4S.
      This natural antibody was quantified by flow cytometry and its anti-tumor
      activity was measured by complement-dependent cytotoxicity (CDC) using TGW cells,
      a human NB cell line, as the target. RESULTS: IgM antibody and CDC activity
      against NB could be detectetd in all sera from healthy volunteers and from
      patients with non-malignant surgical dis eases who were age >1 year. The amount
      of IgM antibody and CDC activity in sera from patients with Stage 4 NB at
      diagnosis consistently was low, most likely because of massive absorption by
      tumor cells. In this group of patients, the increased CDC activity detected
      during treatment was indicative of a favorable factor for survival. CONCLUSIONS:
      A natural antibody against NB appears to exist in the sera of Japanese children.
      The sequential assessment of the levels of this antibody in the sera from Stage 4
      NB patients during treatment may serve as a prognostic indicator.

PMID- 11464869
TI  - Decreased wild-type full-length Et-A and -B receptors in neuroblastoma and Ewing
      sarcoma cells.
AB  - BACKGROUND: Endothelins and their receptors, Et-A and Et-B, play an essential
      role in differentiation and migration of neural crest cells. Expression of
      endothelin receptors has been examined in neuroblastoma and Ewing sarcoma cell
      lines. PROCEDURE: RNA was amplified for Et-A and Et-B by RT-PCR. Amplified
      products were cloned into the expression vector pLNCX, which was used to
      transfect CHO cells. Binding characteristics of transfected CHO cells were
      examined. RESULTS: Full-length Et-A mRNA was identified in all cell lines, in
      addition to a truncated Et-A product. CHO cells expressing full-length Et-A bound
      to endothelin, but cells expressing truncated Et-A did not. Full length Et-B mRNA
      was not detected, but two smaller molecular weight products were amplified. These
      are as yet uncharacterised. CONCLUSIONS: These results suggest that endothelins
      and their receptors may be important in the development and biology of
      neuroblastoma and Ewing sarcoma.

PMID- 11464872
TI  - IGFBPs are involved in xenograft development in nude mice.
AB  - BACKGROUND: The insulin-like growth factors (IGFs) are involved in the growth and
      differentiation of neuroblastoma cells. In all biological fluids, they are non
      covalently bound to high-affinity binding proteins (IGFBP-1 to -6) which modulate
      their bioavailability. We previously showed that IGFBP-6 expression is linked to
      the arrest of growth in neuroblastoma cells, whereas IGFBP-2 is associated with
      proliferation. PROCEDURE: To study the role of IGFBP-6 in cell growth, we stably
      IGR-N-91 neuroblastoma cells with a plasmid containing sequences coding for IGFBP
      6 under the control of the cytomegalovirus (CMV) promoter. RESULTS: The incidence
      and size of tumors generated by injecting IGFBP-6-expressing cells into nude mice
      were reduced by factors of 2 and 5, respectively, as compared with those
      generated by injection by control cells. Northern blot analyses if xenografts
      revealed weaker expression of IGF-II, type 2 IGF receptor and IGFBP-2 mRNAs in
      IGFBP-6-expressing cthan in control xenografts. IGFBP-6 may therefore reduce the
      expression of IGF-II (which induces tumour development) at a transcriptional
      level. Conversely, containing IGFBP-2 cDNA under the control of CMV promoter grew
      three to four times as fast as normal control xenografts. Northern blot analyses
      revealed weaker expression of intact IGFBP-3 and IGFBP-1 in IGFBP-2-expressing
      than in control xenografts. CONCLUSIONS: IGFBP-1 and intact IGFBP-3 expression
      both enhance IGF bioavailability which promotes tumour growth. Although the
      mechanisms of action of IGFBP-2 and IGFBP-6 remain to be elucidated, an inverse
      relationship appears to exist between the two binding proteins, IGFBP-2 being
      involved in proliferation and IGFBP-6 in its arrest.

PMID- 11464871
TI  - Evidence of chromaffin oxygen sensing in neuroblastoma.
AB  - With the aid of IGF2 and VEGF in situ hybridization; tyrosine hydroxylase,
      chromogranin A, and Ki67 immunohistochemistry; and TUNEL staining applied to a
      large series of clinical neuroblastomas and to an animal model, we show here that
      stroma-poor neuroblastomas show evidence of chromaffin differentiation similar to
      that of type 1 small intensely fluorescent (SIF) cells and that this occurs in a
      vascular-dependent fashion, indicating a role for local tumor hypoxia in the
      differentiation process.

PMID- 11464875
TI  - Neuroblastoma cells provoke Schwann cell proliferation in vitro.
AB  - BACKGROUND: A subset of human neuroblastomas (NBs) has the capacity to mature
      completely, imitating sympathetic ganglia. Previously, we showed that the
      neuronal population in spontaneously maturing NBs usually has a near-triploid DNA
      content without 1p deletions, and we concluded that the constantly diploid
      Schwann cells (SCs) do not belong to the neoplastic component of these tumours.
      We therefore hypothesised that NB cells are able to stimulate SC proliferation,
      and that SCs trigger NB differentiation. PROCEDURE: We performed in vitro
      experiments to test this model and to test whether SCs can also influence the
      growth of aggressive NBs. Human SCs were co-cultivated with NB tumours and cell
      lines, and were harvested after defined time intervals. Proliferative activity of
      the SCs and the NB cells was determined by visualisation of 5-bromo-2'
      deoxyuridine (BrdU) incorporation or Ki-67 staining. Neurite outgrowth and
      neurofilament (NF) expression were analysed immunocytochemically and apoptotic
      rate was determined by a terminal deoxynucleotidyl transferase-mediated dUTP-X
      fluorescein nick end labelling (TUNEL) assay. RESULTS: Human NB tumours or cell
      lines unequivocally increased the proliferation of SCs in vitro. In cocultivated
      NB cells, the proliferative activity was not altered in the first days of
      cocultivation, although neurite outgrowth and NF expression were enhanced.
      However, after 10 days, the mitotic rate of neuroblastic cells decreased and the
      apoptotic rate showed a marked increase. CONCLUSIONS: The results of the
      cocultivation experiments provide an experimental hint that the in vivo growth of
      SCs in NBs is caused by the neoplastic neuroblasts, and they also indicate that
      cells from peripheral nerves can influence the growth of aggressive NB cells if
      cocultivated.

PMID- 11464873
TI  - Biological aspects of neuroblastomas identified by mass screening in Quebec.
AB  - BACKGROUND: Neuroblastoma has several characteristics that suggest that
      preclinical diagnosis might improve outcome. Therefore, the Quebec Neuroblastoma
      Screening Project was undertaken from 1989 to 1994 to examine infants at 3 weeks
      and 6 months by measuring urinary catecholamine metabolites. PROCEDURE: Over the
      5-yr period, 45 tumors were detected by screening, 20 were identified clinically
      prior to the third week, and 64 were identified clinically at a later time. We
      analyzed available tumors for Shimada histopathology, tumor ploidy, MYCN copy
      number and serum ferritin. RESULTS: Of the tumors detected by screening, only 2
      of 45 tested had unfavorable histology, 2 of 45 had diploid or tetraploid DNA
      content, 0 of 43 had MYCN amplification, and 4 of 44 had elevated serum ferritin.
      All of these patients are alive and well. The 20 patients detected prior to the 3
      week screen had similar biological characteristics. In contrast, of the patients
      detected clinically after 3 weeks of age, 19 of 51 testedhad unfavorable
      histology, 25 of 66 had diploid or tetraploid tumors, 12 of 56 had MYCN
      amplification, and 14 of 54 had elevated ferritin. CONCLUSIONS: The difference
      between the screened and clinically detected cases was highly significant for
      each biological variable. Preliminary data on other biological variables, such as
      neurotrophin expression and allelic loss on 1 p in these patients are consistent
      with the above findings. These data suggest that mass screening for neuroblastoma
      at or before 6 months of age detects almost exclusively tumors that have
      favorable biological characteristics, many of which might have regressed
      spontaneously. Thus, continued mass screening for neuroblastoma at 6 months is
      unlikely to accomplish its intended goal, and should probably be discontinued.

PMID- 11464874
TI  - Observation of untreated patients with neuroblastoma detected by mass screening:
      a "wait and see" pilot study.
AB  - BACKGROUND: Recent studies have indicated that mass screening for neuroblastoma
      detects tumors that otherwise would have regressed spontaneously without
      recognition. Therefore, we started an observation program for these patients to
      determine how frequently spontaneous regression occurs. PROCEDURE: Eighteen
      patients were detected by mass screening between June 1994 and December 1996.
      Eight of these cases matched the following criteria and entered the observation
      program: Stage I or II, less than 5 cm in diameter; no involvement of large
      vessels or organs; not difficult to resect; informed consent. If there were an
      increase in tumor size, an elevation of tumor markers, or evidence of metastasis,
      the tumor would be immediately resected. RESULTS: Five of the eight cases showed
      spontaneous regression. Although the remaining three tumors were resected 6-10
      months after diagnosis, all patients survived without evidence of recurrence.
      CONCLUSIONS: At least 60% of neuroblastoma cases who entered our observation
      program regressed spontaneously.

PMID- 11464876
TI  - Relationship between histopathological features, MYCN amplification, and
      prognosis: a UKCCSG study. United Kingdom Children Cancer Study Group.
AB  - Histological sections from 231 patients with neuroblastoma were reviewed and
      morphological features and their relationship to age, stage, MYCN amplification
      (in 128 tumours by Southern analyses), and clinical outcome (based on Shimada
      risk grouping) determined. Stage 4 disease was associated with poorly
      differentiated and undifferentiated tumours (P = 0.001), an MKI of >2% (P<
      0.001), and Shimada unfavourable histology (UHi) P< 0.0001. In univariate
      analysis MKI was significant in predicting a poorer relapse-free survival (RFS),
      low vs. intermediate and high (P< 0.001). Age, MYCN amplification, and Shimada UH
      also emerged as significant variables. There was a higher proportion of MYCN
      amplified tumours with Shimada UH (P = 0.03), and this group had a decreased RFS
      (P = 0.002). In patients with Shimada FH, MYCN amplification did not
      significantly predict a poor prognosis. In those with stage 4 disease, Shimada
      classification was not significant in predicting survival (P = 0.97); the same
      was true for those over the age of 1 year (P = 0.66). In multivariate analysis,
      MYCN amplification and Shimada UH both emerged as independent prognostic factors.
      In conclusion, morphological features assigned some subsets of patients to
      prognostic risk groups. Most MYCN-amplified tumours have unfavourable histology
      and a poorer prognosis. However, in patients with stage 4 disease and those over
      the age of 1 year, other factors that may influence prognosis should be
      determined.

PMID- 11464877
TI  - Reversal of multidrug resistance-associated protein-mediated drug resistance in
      cultured human neuroblastoma cells by the quinolone antibiotic difloxacin.
AB  - BACKGROUND: We have recently shown that high-level expression of the multidrug
      resistance-associated protein (MRP) gene is a powerful independent predictor of
      poor outcome in neuroblastoma. The clinical implication of these findings is that
      MRP modulators may prove therapeutically useful. PROCEDURE: We therefore
      investigated the ability of difloxacin, a quinolone antimicrobial antibiotic, to
      increase drug cytotoxicity in unselected cultured human neuroblastoma cells. Drug
      cytotoxicity was determined using a microtiter assay in neuroblastoma cells
      expressing low (SH-EP), intermediate (NBL-S), or high [BE(2)-C] levels of MRP.
      RESULTS: Difloxacin (50 microg/ml) increased sensitivity to the MRP substrates,
      vincristine, doxorubicin, daunorubicin, and potassium antimony tartrate to an
      extent directly proportional to their level of MRP expression. No change in the
      response to cisplatin, which is not a substrate for MRP, was observed in any of
      the cell lines. CONCLUSIONS: The data demonstrate that difloxacin can reverse
      drug resistance in unselected human neuroblastoma cells and is therefore a
      potential candidate for future clinical trials.

PMID- 11464878
TI  - Effect of CEP-751 (KT-6587) on neuroblastoma xenografts expressing TrkB.
AB  - BACKGROUND: The compound CEP-751 (KT-6587), a potent and selective inhibitor of
      the Trk family of tyrosine kinases, has been shown to inhibit the growth of human
      neuroblastoma (NB) xenografts in nude mice [1]. PROCEDURE: To address its
      mechanism of action, we studied SY5Y, a human NB cell line with no detectable Trk
      expression, and two subclones transfected with TrkB. The transfected clones, SY5Y
      (G8) and SY5Y (G12), expressed moderate and high levels, respectively, of TrkB
      mRNA and protein. These TrkB-expressing subclones and the parental line were then
      grown as xenografts in nude mice, and CEP-751 was used to inhibit TrkB tyrosine
      kinase activity in these xenografts. Animals were treated twice a day with CEP
      751 (21 mg/kg), or with the carrier vehicle as a control. TrkB expression in the
      resultant tumors was examined by quantitative RT-PCR. The effect of CEP-751 on
      TrkB activation by BDNF was examined in G12 cells in culture by
      immunoprecipitation with antipan Trk antiserum, followed by Western blot analysis
      using antiphosphotyrosine antibodies. To determine if CEP-751 was causing
      apoptosis, the TUNEL assay was used. RESULTS: CEP-751 had little effect on the
      growth of SY5Y tumors, but did slow the growth rate of the C8 and G12 tumors. The
      daily growth rate of the treated tumors was 0.16, 0.13, and 0.10 cm3,
      respectively, for the SY5Y, G8, and G12 tumors. RT PCR analysis confirmed the
      expression of TrkB in G8 and G12, but not in SY5Y tumors. Activation of TrkB by
      BDNF in G12 cells was inhibited by CEP-751 in a dose dependent fashion. The
      treated tumors showed marked evidence of apoptosis. CONCLUSIONS: These data
      suggest that the effect of CEP-751 is due, at least in part, to its inhibition of
      TrkB kinase, and that CEP-751 may become a useful therapeutic tool for the
      treatment of aggressive neuroblastomas, which often express TrkB.

PMID- 11464879
TI  - Immunotherapeutic strategies in neuroblastoma: antitumoral activity of
      deglycosylated Ricin A conjugated anti-GD2 antibodies and anti-CD3xanti-GD2
      bispecific antibodies.
AB  - BACKGROUND: The antigen GD2 is selectively expressed on the surface of
      neuroblastoma cells, and is detected by the monoclonal antibody BW704. In this
      study, we describe the antitumoral capacity of the immunotoxin BW704dgA (BW704
      conjugated to deglycosylated ricin A), and of anti-CD3xanti-GD2 bispecific
      antibodies that are capable of redirecting cytotoxic T cells towards
      neuroblastoma cells. We further investigate the in vivo activity of BW704dgA
      immunotoxins in a human neuroblastoma model in SCID mice. PROCEDURE: BW704dgA
      immunotoxins were injected i.p. as a single close (48 microg/mouse) on day 4 or
      divided into three doses on day 4, 5, and 6 after i.v. inoculation of the human
      neuroblastoma cell line IMR5-75. RESULTS: The mean survival time (MST) of
      BW704dgA treated animals was significantly increased (MST 49 days) compared to
      the control animals treated with irrelevant immunotoxin, unconjugated BW704, or
      control buffer (MST 33 to 39 days, P < 0.0001), without differences in the
      application schedules. Anti-CD3xanti-NP antibodies and NP-conjugated GD2
      antibodies (BW704-NP) were used in a cytotoxicity assay with cytotoxic T-cells as
      effectors, and tracer labeled neuroblastoma cell line IMR5 as target cells. Anti
      CD3xanti-NP antibodies, together with BW704-NP, showed increased cytotoxic
      activity compared to the incubation with CD3xanti-NP antibodies alone or with
      unconjugated anti-GD2. Additionally, a dose-dependent effect of NP-conjugated
      anti-GD2-antibodies upon the lysis of the target cells could be demonstrated. In
      this report, we describe two immunotherapeutic approaches using GD2 binding BW704
      antibodies, modified as immunotoxin and a bispecific antibody, for the targeting
      and elimination of neuroblastoma cells. CONCLUSIONS: We envisage a combined
      immunotherapeutic regimen consisting of BW704dgA mediated stem cell purging,
      followed by a systemic treatment with anti-CD3xanti-GD2 bispecific antibodies in
      neuroblastoma.

PMID- 11464882
TI  - Etoposide toxicity on human neuroblastoma cells in vitro is enhanced by
      preceeding hyperthermia.
AB  - BACKGROUND: Thermal enhancement has been proven in vitro for the cytotoxic effect
      of alkylants and platinum compounds, not, however, for etoposide, which acts
      synergistically to these drugs. PROCEDURE: Our in vitro study on a neuroblastoma
      cell line confirmed previous results in other tumor models that the cytotoxicity
      of etoposide (12.8% as compared to untreated controls) is not enhanced by
      simultaneous heating to 40 or 42 degrees C for 1 hr (11.9%), as jugded by colony
      forming assay. RESULTS: The same temperature applied 24 hr before the drug
      resulted in a significant decrease of colonies (6.1%). Double treatment with
      etoposide within a 24-hr-interval yielded a similar result (5.6%). The colony
      number could be further decreased by adding hyperthermia 24 hr before the second
      treatment (1.3%). CONCLUSIONS: We demonstrate in vitro that the enhancing effect
      of increased temperature on the cytotoxicity of etoposide on neuroblastoma cells
      is not absent, but depends on scheduling. The temperature range used is
      achievable in total body hyperthermia. Thus, our results are relevant for
      possible treatment of disseminated neuroblastoma.

PMID- 11464880
TI  - Antiangiogenic therapy inhibits human neuroblastoma growth.
AB  - BACKGROUND: Angiogenesis plays a crucial role in the progression and metastasis
      of malignant solid tumors. In many types of cancer, including neuroblastoma, high
      tumor vascularity correlates with poor outcome. Recently, a number of angiogenic
      inhibitors have been identified that had antitumor activity in preclinical
      studies. PROCEDURE: To investigate the effect of the antiangiogenic agent TNP-470
      on neuroblastoma tumor growth, we treated nude mice with TNP-470 after they were
      inoculated subcutaneously with 5 x 10(6) cells from the MYCN-amplified, human
      neuroblastoma cell line NBL-W-N. RESULTS: TNP-470 did not significantly affect
      tumor growth when it was administered to mice with large tumors (>600 mm3).
      However, when TNP-470 was administered in the setting of microscopic disease 12
      hr following tumor cell inoculation, treated mice had a significantly improved
      tumor-free survival at 12 weeks (P < 0.001), and overall survival at 45 weeks (P
      < 0.001), compared to control animals. CONCLUSIONS: Our studies suggest that TNP
      470 treatment may be most effective if it is administered in the setting of
      microscopic disease. We speculate that TNP-470 may inhibit neuroblastoma growth
      in children if treatment is initiated following intensive multimodality therapy,
      when residual disease is minimal.

PMID- 11464881
TI  - Disaloganglioside GD2 loss following monoclonal antibody therapy is rare in
      neuroblastoma.
AB  - BACKGROUND: Gangliosicle GD2 is abundant on human neuroblastoma (NB). Monoclonal
      antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen
      negative clones can escape immune-mediated attack leading to clinical resistance
      or recurrence. PROCEDURE: Among 95 evaluable patients treated intravenously with
      3F8 (94 Stage 4, 1 Stage 3), 66 received nonradiolabeled 3F8, 11 received 131
      iodine-labeled-3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18
      received both forms of treatment. Prior to treatment, 90 patients tested positive
      for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor
      immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy (n = 2).
      RESULTS: Of 62 patients who had refractory or recurrent neuroblastoma following
      3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow
      immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole
      tumor that lost GD2 expression underwent phenotypic transformation into a
      pheochromocytoma-like tumor. CONCLUSIONS: The persistence of GD2 expression in
      refractory or recurrent NB suggests that complete antigen loss is an uncommon
      event and cannot account for treatment failure.

PMID- 11464884
TI  - Molecular cytogenetic definition of 17q translocation breakpoints in
      neuroblastoma.
AB  - BACKGROUND: Unbalanced translocations resulting in the gain of material from 17q
      are the most common chromosomal changes in neuroblastoma and are associated with
      poor patient survival, and are established indicators of bad prognosis.
      PROCEDURE: We have used 13 fluorescent in situ hybridisation probes to map 17q
      translocation breakpoints in ten neuroblastoma cell lines and 21 primary tumours.
      RESULTS: At least seven different breakpoints have been identified, all localised
      within the proximal half of 17q (53-68 cM, 17cen-17q22). CONCLUSION: These
      results suggest that the dosage of a gene, or genes, in 17q22-qter is responsible
      for the clinical effects of 17q gain, rather than the disruption of a specific
      gene.

PMID- 11464886
TI  - Automatic detection and genetic profiling of disseminated neuroblastoma cells.
AB  - BACKGROUND: Rare tumor cells circulating in the hematopoietic system can escape
      identification. On the other hand, the nature of these cells, positive for an
      immunologiCal tumor marker, cannot be determined without any genetic information.
      PROCEDURE: To overcome these problems a novel computer assisted scanning system
      for automatic cell search, analysis, and sequential repositioning was developed.
      This system allows an exact quantitative analysis of rare tumor cells in the bone
      marrow and peripheral blood by sequential immunological and molecular cytogenetic
      characterization. RESULTS AND CONCLUSIONS: In that virtually all tumor cells in a
      mixing experiment could be recovered unambiguously, we can conclude that the
      sensitivity of this approach is set by the number of cells available for
      analysis. Sequential FISH analyses of immunologically positive cells improve both
      the specificity and the sensitivity of the microscopic minimal residual disease
      detection.

PMID- 11464885
TI  - Outcome prediction by molecular detection of minimal residual disease in bone
      marrow for advanced neuroblastoma.
AB  - BACKGROUND: We have determined whether sequential molecular detection of minimal
      residual disease (MRD) in bone marrow (BM) could predict the outcome of patients
      with advanced neuroblastoma (NB). PROCEDURE: Bone marrow samples from 19 patients
      over 12 months of age with stage 4 neuroblastoma were sequentially examined for
      tumor cell contamination by detecting tyrosine hydroxylase (TH) mRNA using
      reverse transcription-polymerase chain reaction (RT-PCR). All patients received
      repetitive multi-drug chemotherapy including cisplatin, cyclophosphamide or
      ifosphamide, adriamycin, and etoposide or vincristine. Seventeen patients
      received myeloablative therapy with hematopoietic stem cell transplantation after
      achieving complete remission. RESULTS: All but one patient were histologically
      positive for tumor cells in BM samples at diagnosis, and they became negative for
      tumor cells within 3 months histologically. By the RT-PCR analysis, all patients
      were positive for TH mRNA in BM samples at diagnosis, and they became negative
      for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM
      samples became negative for TH mRNA within 4 months after the start of
      chemotherapy remained alive without evidence of disease (median 61 months, range
      20-76). In contrast, 12 of 13 patients whose BM samples remained positive at that
      time developed relapse and 10 of them died of disease (median 24 months, range 13
      43). There was a statistically significant difference in survival between the two
      groups (P < 0.05). No significant difference of clinical characteristics by the
      MRD positivity at 4 months after the start of chemotherapy. CONCLUSIONS:
      Persistence of MRD in BM at 4 months after the start of chemotherapy could
      predict poor prognosis in advanced neuroblastoma.

PMID- 11464883
TI  - Preclinical and clinical aspects on the use of amifostine as chemoprotector in
      neuroblastoma patients.
AB  - BACKGROUND: In several studies in adults, amifostine (WR-2721) and its active
      metabolite WR-1065 have shown protection against myelo- and nephrotoxicity of
      chemotherapeutic agents without compromising cytotoxic efficacy to the tumor.
      PROCEDURE: In the present study, the effect of amifostine and WR-1065 on
      neuroblastoma tumor growth and its protective potential for hematotoxicity were
      investigated. Neither amifostine nor WR-1065 reduced the cytotoxic effect of six
      drugs commonly used for this tumor when tested on neuroblastoma cells in vitro.
      RESULTS: In mice carrying human xeno-transplanted neuroblastoma, tumor growth and
      antitumor activity of chemotherapy were unaffected by amifostine. In addition,
      hematotoxicity of alkylators was relieved in some cases. In patients with
      neuroblastoma, amifostine only slightly reduced bone marrow toxicity and was
      highly emetogenic. CONCLUSIONS: Therefore, amifostine warrants further
      investigation before its widespread clinical use in the treatment of children
      with neuroblastoma.

PMID- 11464887
TI  - Detection of microscopic disease: comparing histology, immunocytology, and RT-PCR
      of tyrosine hydroxylase, GAGE, and MAGE.
AB  - BACKGROUND: We first explored the use of multiple molecular markers to overcome
      tumor heterogeneity. Sixty-seven neuroblastoma (NB) tumors were tested for the
      expression of GAGE, MAGE-2, MAGE-2, MAGE-3, and MAGE-4 by RT-PCR and then
      chemiluminescence; 82% of tumors had detectable GAGE, and 88% expressed at least
      one of the four MAGE genes. PROCEDURE AND RESULTS: By combining GAGE and MAGE, 64
      of 67 (95%) of tumors became detectable; 17 of 67 coexpressed all five molecular
      markers. Neither GAGE nor MAGE expression correlated with stage. GAGE was found
      to have the broadest (18 of 18) expression among stage 4 tumors. Two hundred
      fifty-nine bone marrows from 99 patients were then studied for NB positivity by
      four detection methods: histology, immunocytology, and molecular detection by
      GAGE and tyrosine hydroxylase (TH) mRNA. Two hundred seven samples were NB
      positive by one detection method. All four techniques were comparable in
      detecting tumor cells at diagnosis and at relapse. GAGE and immunocytology were
      far more sensitive than histology and TH mRNA when marrows were sampled during
      chemotherapy and at the time of clinical remission. CONCLUSIONS: By combining
      multiple molecular markers and independent screening techniques, we may be able
      to overcome tumor heterogeneity and expedite the detection of microscopic disease
      in the clinical management of neuroblastoma.

PMID- 11464888
TI  - Minimal residual disease at the time of peripheral blood stem cell harvest in
      patients with advanced neuroblastoma.
AB  - BACKGROUND: Despite treatment with high-dose myeloblative chemotherapy and
      peripheral blood stem cell (PBSC) rescue, a high proportion of children with
      neuroblastoma relapse and die. Re-infusion of PBSC contaminated with tumour at
      the time of autologous transplantation may play a significant role in this
      relapse. In this study the frequency of tumour contamination in PB from children
      with neuroblastoma has been investigated. PROCEDURE: Minimal residual disease was
      measured using RT-PCR for tyrosine hydroxylase (TH) mRNA in PBSCs from patients
      with advanced neuroblastoma. PBSCs from 18 patients in complete clinical
      remission were studied. RESULTS: Studies in other cancers have suggested minimal
      contamination of PBSCs with tumour cells; TH mRNA was detected by RT-PCR in 50%
      (9/18) of PBSC harvests. Seventy-seven percent (7/9) of patients with TH mRNA in
      PBSC died of disease compared to 44% (4/9) who were TH mRNA-negative.
      CONCLUSIONS: Therefore, the presence of TH mRNA in PBSCs appeared to be
      associated with an unfavourable outcome, although this was not statistically
      significant. In summary, RT-PCR for TH mRNA is a sensitive method for the
      identification of tumour cells in PBSC harvest. The presence of TH mRNA in PBSC
      harvest may reflect disease status and be associated with an unfavourable
      outcome, although long-term clinical outcome studies in a larger patient cohort
      are required.

PMID- 11464889
TI  - Evaluation of catecholamine metabolites, mIBG scan, and bone marrow cytology as
      response markers in stage 4 neuroblastoma.
AB  - BACKGROUND: The early biological response has been proved an excellent predictor
      in acute lymphoblastic leukemia and nephroblastoma. We asked whether
      catecholamine metabolites, mIBG scan, and bone marrow evaluation might be
      relevant response markers in disseminated neuroblastoma. PROCEDURE: Three hundred
      sixty-seven unselected stage 4 neuroblastoma patients treated according the
      German cooperative trial NB90 were entered into the study. Catecholamine plasma
      and urine levels were centrally determined by gas chromatography/ mass
      spectrometry. Bone marrow cytology and mIBG scans were evaluated by local
      investigators. RESULTS: At diagnosis, mIBG scan was positive in 306 patients
      (92%), borderline in seven patients (2%), and negative in 19 patients (6%). Bone
      marrow aspirates were cytologically positive in 292 patients (84%) and negative
      in 57 patients (16%). Plasma catecholamine levels were elevated in 79% (206 of
      260 patients.), urinary levels in 91% (307 of 338 patients). The outcome of
      patients with normalized mIBG scan after four courses of chemotherapy [5 year EFS
      (event free survival) 0.22 +/- 0.07] was not superior to the outcome of patients
      with still abnormal uptake (5 year EFS 0.30 +/- 0.05). The event free survival of
      patients with still positive bone marrow aspirates after four courses (0.16 +/-
      0.06) was inferior to the EFS of patients with negative bone marrow aspirates
      (0.26 +/- 0.04, P = 0.0054). Urinary catecholamine normalization after four
      cycles of chemotherapy (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10) had no
      influence on outcome, whereas plasma catecholamine normalization after the first
      (5 year EFS 0.40 +/- 0.09 versus 0.14 +/- 0.07, P= 0.0364) or the fourth cycle (5
      year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10, P = 0.0242) indicated a better
      outcome. CONCLUSIONS: These data show that serial plasma catecholamine levels and
      bone marrow aspirates in the course of the disease are useful tools in predicting
      outcome.

PMID- 11464890
TI  - Somatostatin receptor type 2 gene expression in neuroblastoma, measured by
      competitive RT-PCR, is related to patient survival and to somatostatin receptor
      imaging by indium -111-pentetreotide.
AB  - BACKGROUND: We previously reported that human neuroblastoma cell lines and
      primary neuroblastoma tumors expressed a variable amount of mRNA for type 2
      somatostatin (sst2) receptor gene. We also found that high level of sst2
      expression were positively related to patient survival. PROCEDURE: We studied
      retrospectively 49 primary neuroblastomas. To detect and measure sst2 mRNA
      expression we developed a quantitative RT-PCR based on competitive PCR. When
      possible the number of MYCN copies was also measured with competitive PCR.
      RESULTS;. We found that the lowest level of sst2 mRNA was detected in advanced
      stages of neuroblastomas (stage IV) when compared with the other stages (P<
      0.005). Patients with high levels of sst2 expression (>7 x 10(7) molecules/microg
      RNA) had a cumulative survival better than those with low sst2 expression (P <
      0.0005). This predictive independent value of sst2 (P= 0.005) is retained after
      stratification for N-myc amplification. Finally we verified that the ex vivo sst2
      gene expression in tumor samples was positively related (P < 0.01) to the in vivo
      semiquantitative determination of sst2 protein, assessed by 111In-pentetreotide
      imaging. CONCLUSIONS: Our data indicate that the measurement of sst2 mRNA
      measurement could represent a relevant tool in the prediction of neuroblastoma
      outcome, independently from MYCN amplification.

PMID- 11464891
TI  - N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children
      diagnosed over 1 year of age.
AB  - BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive
      chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994]
      but with lower dosing of vincristine) for induction, surgical resection and 2100
      cGy hyperfractionated radiotherapy for local control, and for consolidation,
      targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody
      and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The
      chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of
      doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and
      cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7.
      131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates
      stem-cell support. RESULTS: Of the first 24 consecutive previously untreated
      patients more than 1 year old at diagnosis, 22 were stage 4 and two were
      unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21
      of 24 patients. Twenty patients to date have completed treatment with 131I-3F8,
      and 15 patients have completed all treatment. With a median follow-up of 19
      months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities
      were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited
      pain and urticaria during antibody treatment. Late effects include hearing
      deficits and hypothyroidism.

PMID- 11464892
TI  - Neuroblastoma: changing incidence and survival in young people aged 0-24 years. A
      report from the North of England Young Persons' Malignant Disease Registry.
AB  - BACKGROUND AND PROCEDURE: Population based data for neuroblastoma in children and
      young adults under 25 years at diagnosis were ascertained from the Northern
      Region Young Persons' Malignant Disease Registry for the period 1968-1995. Age
      standardised incidence rates were calculated (ASR) and changes in incidence and
      survival were investigated. Over the study period 144 patients were registered,
      of these 136 were children under 15 years at diagnosis (median age: 2.2 years,
      ASR: 8.6 cases per million children per year), and 8 were 15-24 years (ASR 0.6).
      RESULTS AND CONCLUSIONS: Incidence of childhood neuroblastoma in the North of
      England increased significantly over time; ASRs were 5.8 for 1968-1981 and 9.5
      for 1982-1995 (rate ratio: 1.6, 95%; CI 1.2-2.3). The increase in incidence was
      seen in both infants and older children, and in both low stage and advanced
      disease. Overall 5 year survival was 15% for 1968-1981 and 40% for 1982-1995 (P <
      0.0001). Significant improvements in survival were documented across different
      stage and age-groups, including those over 1 with stage 4 disease (0% versus 18%,
      P < 0.0001). Further research is needed to investigate the reasons for the
      increasing incidence of neuroblastoma.

PMID- 11464893
TI  - Late relapse and prognosis for neuroblastoma patients surviving 5 years or more:
      a report from the European Neuroblastoma Study Group "Survey".
AB  - BACKGROUND AND PROCEDURE: Most deaths from neuroblastoma occur within 2 years of
      diagnosis but there have been several anecdotal reports of relapse and death
      after much longer periods of follow up. In order to investigate and quantify the
      risk of late events we analysed data for patients registered with the European
      Neuroblastoma Study Group between 1982 and 1990. Out of a total of 1,277 children
      registered, 427 were alive with follow-up beyond 5 years from diagnosis (median
      follow-up of 8.8 years, range 5-14 years). Of these 406 were in remission with no
      prior recurrence, 16 were in remission having experienced a relapse prior to 5
      years, and 5 were alive with progressive disease. RESULTS: For the 406 patients
      in remission with no prior relapse the 10 year progression free survival (PFS)
      was 96% (CI 94-98). For those aged over 1 year with stage 4 disease at diagnosis
      10 year PFS was 88% (CI 79-96) compared to 98% (CI 97-99) for other patients
      combined, P< 0.001. In a multivariate analysis of all 422 patients in remission
      at 5 years, significant risk factors for subsequent relapse were age > 1 yr with
      stage 4 disease at diagnosis (relative risk 10.5, P < 0.001) and prior relapse
      (RR 4.2, P= 0.01). CONCLUSIONS: The results of this study emphasise the
      importance of longterm follow-up of patients and the need for late monitoring of
      clinical trials in children with neuroblastoma. They also provide a baseline for
      comparison with future and hopefully more effective treatment programmes.

PMID- 11464894
TI  - OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.
AB  - BACKGROUND: This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4
      neuroblastoma patients over 1 year of age. PROCEDURE: Ninety-five patients with
      stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5
      mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600
      mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was
      haematological recovery. RESULTS: Seventy out of ninety-five (74%) patients
      completed seven or more courses and were evaluable for toxicity. Of these 70
      patients, 33% had more than three episodes of fever and sepsis, 35% required more
      than five blood or platelet transfusions, 36% had grade 2 or more
      gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction
      in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death.
      CONCLUSIONS: OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over
      1 year of age.

PMID- 11464895
TI  - Allelic deletion at chromosome bands 11q14-23 is common in neuroblastoma.
AB  - BACKGROUND: Neuroblastoma tumorigenesis may involve the differential inactivation
      of multiple tumor suppressor genes. Recent data have suggested that a
      neuroblastoma suppressor gene may be located on the long arm of chromosome 11
      (11q). PROCEDURE: We therefore analyzed 295 primary neuroblastomas from a
      representative group of patients for loss of heterozygosity (LOH) at 25
      polymorphic markers spanning 11q. RESULTS: LOH was observed in 129 primary
      neuroblastomas (44%), and a common region of LOH mapped to 11q14-23. No
      correlation was found between 11q LOH and adverse prognostic variables, but a
      strong inverse relationship between 11q LOH and MYCN amplification (P < 0.001)
      was observed. There was no difference in overall survival when patients were
      stratified by 11q LOH status. However, 11q LOH was associated with a decreased
      overall survival probability when patients whose tumors had a single copy of MYCN
      were analyzed separately (P = 0.008). CONCLUSION: These data support the
      hypothesis that a tumor suppressor gene mapping within 11q14-23 is frequently
      inactivated during the malignant evolution of neuroblastoma.

PMID- 11464896
TI  - Generation of a humanised single chain Fv (Scfv) derived from the monoclonal Eric
      1 recognising the human neural cell adhesion molecule.
AB  - BACKGROUND: Murine monoclonal antibody (MoAb) ERIC-1 recognises an epitope on the
      neural cell adhesion molecule (NCAM) whose expression in paediatric and adult
      tissues is confined mainly to the brain, peripheral nerve, and adrenal medulla.
      Anti-NCAM antibodies have been used for the treatment and diagnosis of a number
      of tumours, including neuroblastoma. However, whole antibody exhibits poor
      penetration into solid tumour deposits and rapid systemic clearance upon repeated
      administration due to development of a human antimouse antibody (HAMA) response.
      PROCEDURE: To overcome these problems, recombinant DNA techniques have been used
      to humanise and assemble the ERIC-1 immunoglobulin variable heavy (VH) and light
      (VL) chains into a single chain Fv (scFv). RESULTS: Three humanised scFv clones
      were identified which differ from the predicted humanised sequence by occasional
      amino acid changes, but these maintain the same specificity as the original ERIC
      1 MoAb. CONCLUSIONS: The humanised scFv may prove to be a useful reagents in the
      treatment and diagnosis of a variety of neuroectodermal tumours and can clearly
      form a suitable template for the generation of a fully humanised ERIC-1 MoAb.

PMID- 11464897
TI  - Localised and unresectable neuroblastoma in infants: excellent outcome with
      primary chemotherapy. Neuroblastoma Study Group, Societe Francaise d'Oncologie
      Pediatrique.
AB  - PROCEDURE: Infants with neuroblastoma (NB) were assessed according to INSS
      recommendations, including MIBG scan and extensive bone marrow staging to
      eliminate metastatic spread. Patients with unresectable tumour received
      chemotherapy, including two courses of carboplatin-etoposide (CE) and two of
      vincristinecyclophosphamide-doxorubicin (CAdO). Post-operative treatment was to
      be given only in infants with MYCN amplification. Between 1990 and 1994, 52
      consecutive children were registered. RESULTS: Among the 44 patients who received
      CE as a first course, the response rate was (66%) and the primary could be
      removed in all children but one, who was in remission. The toxicity was mainly
      haematological and was always manageable. The 5 year overall survival (OS) and
      event-free survival (EFS) were 94 and 90 +/- 8%, respectively, with a median
      follow-up of 48 months. The outcome of infants with no MYCN amplification was
      excellent; OS and EFS were, respectively, 97 and 94%. CONCLUSIONS: Chemotherapy
      allows surgical excision and excellent outcome in infants with localised and
      unresectable NB. Less intensive Chemotherapy should be investigated in such
      patients.

PMID- 11464898
TI  - Initial characterization of the apoptosis-inducing receptor for natural human
      anti-neuroblastoma IgM.
AB  - BACKGROUND: Human neuroblastoma (NB) cells contain a 260 kDa surface antigen (NB
      p260), which serves as receptor for natural human IgM antibodies (anti-NB IgM).
      Upon binding to NB-p260, these antibodies induce apoptosis in human NB cells.
      PROCEDURE AND RESULTS: In this study, we purified NB-p260 to homogeneity from
      human LA-N-1 NB cells by sequential ion exchange chromatography followed by
      preparative SDS gel electrophoresis. Purified NB-p260 exhibited rapid
      autodegradation despite the presence of various protease inhibitors. The
      autodegradation process precluded extensive N-terminal sequencing. However, from
      repeat N-terminal sequence analysis, a consensus sequence of seven amino acid
      residues emerged that exhibited significant homology to the subunit c of the
      human mitochondrial ATP synthase, a hydrophobic membrane protein of 7.6 kDa.
      Western blot analyses demonstrated that purified NB-p260 was recognized by
      polyclonal antibodies raised against both subunit c-containing storage bodies and
      a synthetic peptide consisting of amino acid residues 32-45 of subunit c. In
      addition to peptide sequences related to subunit c, NB-p260 also contained
      epitopes related to the human heat shock protein HSP90. In Western blots, a
      monoclonal anti-HSP90 antibody reacted with purified NB-p260 as well as with a
      predominant protein fragment of approximately 90 kDa that appeared during the
      process of NB-p260 autodegradation. The anti-HSP90 antibody was also capable of
      binding to the surface of LA-N-1 cells and inhibiting the binding of human anti
      NB IgM in a dose-dependent manner. CONCLUSIONS: Collectively, our data suggest
      that NB-p260, the apoptosis-mediating receptor for natural human anti-NB IgM,
      represents a novel surface protein of human NB cells containing polypeptide
      sequences related to the subunit c of the mitochondrial ATP synthase and the heat
      shock protein HSP90.

PMID- 11464899
TI  - Loss of heterozygosity for chromosome 14q in neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is a genetically heterogeneous disease, with subsets of
      tumors demonstrating rearrangements of several genomic regions. Preliminary
      studies from several groups have identified loss of heterozygosity (LOH) for the
      long arm of chromosome 14 (14q) in 20-25% of primary neuroblastomas. PROCEDURE:
      To determine precisely the frequency and extent of 14q deletions, we performed
      LOH analysis for a large series of primary neuroblastomas using a panel of 11
      highly polymorphic markers. RESULTS: LOH was detected in 83 of 372 tumors (22%).
      Although the majority of tumors with allelic loss demonstrated allelic loss for
      all informative markers, 13 cases showed LOH for only a portion of 14q. A single
      consensus region of deletion, which was shared by all tumors with 14q LOH, was
      defined within 14q23-q32 between D14S588 and the 14q telomere. Allelic loss for
      14q was strongly correlated with the presence of 11q LOH (P < 0.001 ) and
      inversely correlated with MYCN amplification (P= 0.04). CONCLUSIONS: LOH for 14q
      was evident in all clinical risk groups, indicating that this abnormality may be
      a universal feature of neuroblastoma tumor development. These findings suggest
      that a tumor suppressor gene involved in the initiation or progression of
      neuroblastoma is located within distal 14q.

PMID- 11464900
TI  - Comprehensive analysis of chromosome 1p deletions in neuroblastoma.
AB  - BACKGROUND: Chromosome 1p deletions are common in advanced neuroblastomas, but
      the biological and clinical implications of this clonal rearrangement remain
      controversial. Previous studies of chromosome 1p loss of heterozygosity (LOH)
      have been limited by analyses of relatively small number of tumors derived from
      heterogeneously assessed and treated patient populations. Therefore, a strictly
      representative cohort of 288 Children's Cancer Group neuroblastoma patients
      treated on the most recent phase III therapeutic trials was identified.
      PROCEDURE: Primary tumors from these patients were analyzed for LOH at precisely
      mapped and highly informative 1p polymorphic loci located from 1p32 to 1p36.3 by
      multiplex PCR. RESULTS: Ninety-three primary tumor specimens (32%) had LOH at
      multiple 1p36 marker loci. All 1p deletions overlapped the previously determined
      smallest region of overlap (SRO). One tumor had a small terminal deletion
      completely within 1p36.3, allowing for further refinement of the 1p36 SRO. We
      found no evidence to support an additional, nonoverlapping region of LOH within
      1p32-36. We confirmed the strong correlation of 1p36 LOH with MYCN amplification
      (P < 0.001), advanced disease stage (P < 0.001), and decreased both 3-year event
      free survival and overall survival probabilities (P< 0.001). When stratified for
      MYCN amplification status or entered into a multivariate analysis, 1p36 LOH
      remained predictive for decreased event-free survival, but not overall survival
      probability. CONCLUSIONS: These data support the hypothesis that inactivation of
      a tumor suppressor gene within 1p36.3 is associated with an increased risk for
      disease relapse.

PMID- 11464901
TI  - Detailed molecular analysis of 1p36 in neuroblastoma.
AB  - BACKGROUND: Several lines of evidence es tablish that chromosome band 1p36 is
      frequently deleted in neuroblastoma primary tumors and cell lines, suggesting
      that a tumor suppressor gene within this region is involved in the development of
      this tumor. PROCEDURE: We analyzed the status of 1p36 in primary neuroblastomas
      and cell lines to define the region of consistent rearrangement. RESULTS: Loss of
      heterozygosity (LOH) studies of primary neuro blastomas identified allelic loss
      in 135 of 503 tumors (27%), with the smallest region of overlap (SRO) defined
      distal to D15214 (1p36.3). No homozygous deletions were detected at 120 loci
      mapping to 1p36.1-p36.3 in a panel of 46 neuroblastoma cell lines. A recently
      identified patient with neuroblastoma was found to have a constitutional deletion
      within 1p36.2-p36.3, and this deletion, when combined with the LOH results,
      defined a smaller SRO of one megabase within 1p36.3. We constructed a
      comprehensive integrated map of chromosome 1 containing 11,000 markers and large
      insert clones, a high-resolution radiation hybrid (RH) map of 1p36, and a P1
      artificial chromosome (PAC) contig spanning the SRO, to further characterize the
      region of interest. Over 768 kb (75%) of the SRO has been sequenced to
      completion. Further analysis of distal 1p identified 113 transcripts localizing
      to 1p36, 21 of which were mapped within the SRO. CONCLUSION: This analysis will
      identify suitable positional candidate transcripts for mutational screening and
      subsequent identification of the 1p36.3 neuroblastoma suppressor gene.

PMID- 11464902
TI  - Genetic analysis of p73 localized at chromosome 1p36.3 in primary neuroblastomas.
AB  - BACKGROUND: Human p73, a novel homolog of p53, has recently been cloned and
      mapped at chromosome 1p36.3, the locus for putative tumor suppressor gene(s) of
      neuroblastoma (NBL) and other cancers. p73, like p53, inhibits growth and induces
      apoptosis in neuroblastoma and osteosarcoma cell lines. PROCEDURE: To test the
      hypothesis that p73 is a NBL suppressor gene, we examined expression, allelo
      typing, and mutation of the p73 gene in primary human neuroblastomas. Loss of
      heterozygosity (LOH) for p73 was performed in 272 primary NBLs using a CT repeat
      polymorphic marker, which we found in intron 9 of the p73 gene. RESULTS: p73 LOH
      was observed in 28 out of 151 (19%) informative cases. The high frequency of p73
      LOH was significantly associated with sporadic neuroblastomas (P< 0.001), MYCN
      amplification (P< 0.001), and advanced stages (P< 0.05). Mutational analyses by
      PCR-SSCP (single strand conformation polymorphism) revealed two mis-sense
      mutations in 140 NBLs, one somatic and one germline. CONCLUSION: Thus, the
      present results have shown that mutation of p73 is infrequent in NBLs, although
      the p73 locus is frequently lost in advanced stage tumors. These suggest that p73
      may not be a tumor suppressor in the classic Knudson manner.

PMID- 11464903
TI  - Genomic and allelic expression status of the p73 gene in human neuroblastoma.
AB  - BACKGROUND AND PROCEDURE: The p53 gene homologue, p73, is located on the 1p36-3
      locus, which is frequently deleted in human neuroblastoma (NB). A survey of 61 NB
      showed that among 33% of informative cases, p73 loss of heterozygosity (LOH)
      occurred in 7 of 20 (35%). RESULTS: LOH pattern of vicinal markers suggested that
      the p73 gene could not be considered as the candidate NB suppressor gene.
      Moreover, comparative measurements of allelic expression in tumors and
      corresponding patient lymphocytes indicate that pure biallelism is much more
      frequent in lymphocytes than in tumors (71% vs 30%, P= 0.05), which suggests that
      disequilibrated allelic expression is associated with NB disease. CONCLUSION:
      Therefore, in the p73 LOH NBs, the p73 gene could be altered in the maintained
      allele not by mutations [Ishimiya et al.: Med Pediatr Oncol, this issue], but
      rather by an abnormal transcription.

PMID- 11464904
TI  - Expression of the putative tumour suppressor gene, p73, in neuroblastoma and
      other childhood tumours.
AB  - BACKGROUND: The recently characterised p53 homologue, p73, has been mapped to
      chromosome 1p36, a region often found deleted in neuroblastoma. Although p73 has
      been implicated as a candidate tumour suppressor for neuroblastoma, mutations in
      the gene appear to be rare, thus suggesting other mechanisms for its aberrant
      behaviour. PROCEDURE: We analysed p73 gene expression in a panel of primary
      neuroblastoma tumours and cell lines, as well as other tumours of childhood,
      using a reverse transcriptase-polymerase chain reaction assay. RESULTS: Although
      low-level p73 expression was detected in 44/45 primary neuroblastoma tumours, no
      association with prognostic markers could be discerned. In no case was the level
      of p73 expression in the primary tumours as high as that observed in p73
      expressing neuroblastoma cell lines. Expression of the p73 gene was also detected
      in 24/34 other childhood tumours. CONCLUSION: Collectively, the data raise doubts
      over the role of this gene as a tumour suppressor in neuroblastoma.

PMID- 11464905
TI  - Multicentre analysis of patterns of DNA gains and losses in 204 neuroblastoma
      tumors: how many genetic subgroups are there?
AB  - PROCEDURE: Analysis of comparative genomic hybridization (CGH) data of 120 tumors
      from four different studies, and data of 84 previously unpublishied tumors,
      allowed delineation of at least six different genetic subsets of neuroblastomas.
      RESULTS AND CONCLUSIONS: A small number of tumors show no detectable imballances.
      A second group of tumors presents with gains and losses of whole chromosomes and
      is found predominantly in prognostically favorable stage 1 and 2 tumors. The
      remaining groups are characterized by the presence of partial chromosome
      imbalances, and are found mostly in stage 3, 4, and 4S tumors. The third group
      shows 17q gain without 11q loss, 1p loss, or MYCN amplification (MNA). The fourth
      group has 1p deletion or MNA, and finally, a fifth group shows 11q loss without
      1p deletion or MNA, and is found mainly in stage 4 tumors. The latter group is
      significantly associated with losses of 3p, 4p, and 14q.

PMID- 11464906
TI  - Analysis of genomic imprinting at 1p35-36 in neuroblastoma.
AB  - BACKGROUND: Deletion of the distal short arm of chromosome 1 occurs in 25-35% of
      primary neuroblastomas, and a putative tumor suppressor gene has been mapped to a
      consensus region of deletion at 1p36.2-36.3. Indirect evidence suggests the
      presence of an imprinted neuroblastoma suppressor gene within this region, as
      well as an additional nonimprinted, proximal suppressor gene, inactivation of
      which correlates with MYCN amplification. PROCEDURE: To test this hypothesis, we
      performed 1p loss of heterozygosity (LOH) studies on a series of neuroblastomas
      for which parental DNA had been collected. PCR-formatted polymorphic markers were
      used to determine the size of the 1p deletion and the parental origin of the
      deleted 1p homologue. RESULTS: Twenty-six neuroblastomas with 1p LOH were
      evaluated. Twenty-four had MYCN amplification, and of these, 15 demonstrated loss
      of the paternally inherited 1p. Two neuroblastomas with a single copy of MYCN
      were evaluated and both had deletion of the paternally inherited 1p, with one
      case exhibiting a small terminal deletion. In addition, we have reviewed 49
      previously reported neuroblastomas where 1p LOH data and the parental origin of
      the deleted lp homologue were available. CONCLUSIONS: Analyzed together, these 75
      neuroblastomas demonstrate random deletion of parental 1p homologues (P = 0.30).
      Further, tumors with smaller deletions (breakpoints distal to D1S201 or D1S7)
      showed a random loss of the parental 1p homologues (P = 0.59), contrary to the
      expected preferential maternal 1p deletion if an imprinted suppressor gene mapped
      to this region. However, 19 tumors with 1p LOH and single copy MYCN had deletion
      of the maternal 1p homologue preferentially (P = 0.02), which does not exclude
      the possibility that loss of an imprinted suppressor gene plays a role in this
      subset.

PMID- 11464907
TI  - Absence of somatostatin receptor expression in vivo is correlated to di- or
      tetraploid 1p36-deleted neuroblastomas.
AB  - BACKGROUND: Poor prognosis in childhood neuroblastoma is associated with
      deletions of chromosome region 1p36 and di/tetraploid DNA content. PROCEDURE:
      Forty-six patients with histopathologically proven neuroblastoma were
      investigated for in vivo expression of somatostatin receptors (SR) by 111In
      pentetreotide scintigraphy. All tumors were analyzed for cytometric DNA content
      and chromosome 1p36 integrity. RESULTS: SR expression was detected in 28 tumors
      (61%) and correlated with young age, localized clinical stage, and favorable
      outcome. Fourteen tumors showed deletion at chromosome 1p36, thirteen of which
      did not show SR expression (P< 0.001). A triploid DNA content was correlated with
      the presence of SR (23 of 25, P< 0.001). No tumor with deletion of chromosome
      1p36 and di/tetra DNA content showed SR expression (chi2 = 29.88, d.o.f. = 2, P <
      0.001). CONCLUSIONS: We conclude that SR expression is related to genetic
      features of prognostic significance. This may be assessed with a minimally
      invasive scintigraphic method.

PMID- 11464908
TI  - Fine mapping of a tumour suppressor candidate gene region in 1p36.2-3, commonly
      deleted in neuroblastomas and germ cell tumours.
AB  - BACKGROUND: A common genetic feature of neuroblastomas, which is also an
      important prognostic factor, is deletion of chromosome region 1p. The deletion of
      1p often involves a deletion of varying size, with a consensus region within the
      most distal bands 1p36.2-3. The neuroblastoma SRO (shortest region of overlap of
      (deletions) presented earlier by our group was defined distally by the cluster of
      loci D1S80/ D1Z2/CDC2L1 and proximally by loci D1S244, i.e., approximately 25 cM.
      The 1p deletions are, however, not restricted to neuroblastoma tumours. In fact,
      a large spectrum of tumour types display deletions to varying degrees of 1p.
      PROCEDURE: We have exploited the possibility of using deletions of other tumour
      types, preferentially that of germ cell tumours, and combining the deletions with
      that of the neuroblastoma SRO. Also in germ cell tumours, distal 1p-deletions
      have been shown to have prognostic significance. RESULTS: We found in our germ
      cell tumours a SRO ranging from D1S508 to D1S200. Interestingly, this region only
      partially overlapped (approximately 5 cm) with our neuroblastoma SRO in region
      D1S508 to D1S244. We have thus focused on analysing this smaller region in the
      search for genes involved in the genesis of different cancers. We have performed
      radiation hybrid mapping of a large number of markers, STSs, ESTs, and others
      known to reside in 1p. We have also initiated the development of a BAC contig of
      the region. FISH, and fibre-FISH mapping of BACs were also performed.
      CONCLUSIONS: The data presented here constitute an ongoing work with the aim of
      identifying and cloning gene(s) important for development of germ cell tumours,
      neuroblastomas, and possibly other tumours.

PMID- 11464909
TI  - Biological characteristics of neuroblastoma with partial deletion in the short
      arm of chromosome 1.
AB  - BACKGROUND: Neuroblastoma shows remarkable heterogeneity, resulting in favorable
      and unfavorable outcomes. It is well known that almost all cases with MYCN
      amplification have a poor prognosis. We have previously reported that unfavorable
      tumors show high telomerase activity, whereas favorable tumors show low or nil
      activity. We also found that the unfavorable neuroblastoma often have a loss of
      heterozygosity (LOH) at the MYCL locus. PROCEDURE: To clarify the biological and
      clinical profiles of tumors with genetic abnormalities of the short arm of
      chromosome 1, we performed deletion mapping on 1p on 92 neuroblastoma tissues and
      corresponding noncancerous samples obtained from 92 cases for 24 micro- or
      minisatellite loci. RESULTS: LOH was detected in at least one locus of 1p in 43
      (47%) cases. All samples were classified into four groups according to the
      deleted pattern: interstitial deletion (group I, n = 20), short terminal deletion
      (group ST, n = 6), large terminal deletion (group LT, n = 17), and without
      detectable deletion (group N, n = 49). All group I cases, whose SRO (shortest
      region of overlap) was at 1p36.1-2, survived disease free, and none of them
      showed MYCN amplification or high telomerase activity except for one case. On the
      other hand, in group LT cases, who showed a large terminal deletion from D1S162
      (1p32-pter), including the SRO of group 1, only 5 out of 17 have survived disease
      free, and 13 showed MYCN amplification or high telomerase activity. The six group
      ST cases showed small terminal deletion from 1p36.3 with modest prognosis,
      similar to the group N. CONCLUSIONS: Thus, we propose three loci, 1p36.1-2, 1p32
      34, and 1p36.3, as the candidate loci of neuroblastoma suppressor genes on
      chromosome 1p responsible for groups I, LT, and ST, respectively. Among them, the
      1p32-34 locus may be associated with aggressiveness of tumor progression,
      possibly due to MYCN amplification and/or telomerase reactivation, while the
      remaining two loci may not.

PMID- 11464910
TI  - Two-dimensional DNA electrophoresis identifies novel CpG islands frequently
      coamplified with MYCN in neuroblastoma.
AB  - BACKGROUND: Amplification of the oncogene MYCN in neuroblastoma has been found to
      correlate with aggressive tumour growth and is used as a predictor of clinical
      outcome. The MYCN amplicon is known to involve coamplification of extensive DNA
      regions. Therefore it is possible that other genes are coamplified in this
      amplicon and that they may play a role in the poor outcome of MYCN amplified
      tumours. PROCEDURE: We have implemented an approach for the two-dimensional
      separation of human genomic restriction fragments to detect and isolate as yet
      unknown amplified sequences in the MYCN amplicon in neuroblastoma. Using this
      approach we have recently cloned a novel gene referred to as NAG that is
      frequently coamplified with MYCN in neuroblastoma. RESULTS AND CONCLUSIONS: We
      report here the identification and cloning of two additional CpG islands that are
      amplified in neuroblastoma. One contains a sequence that is identical to the
      first intron of DDX1. The other represents a novel CpG island that is associated
      with an as yet unidentified gene. We show that the novel CpG island is located in
      close proximity to the MYCN locus on chromosome 2 and is as frequently
      coamplified with MYCN in neuroblastoma as NAG and DDX1.

PMID- 11464911
TI  - Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastomas.
AB  - BACKGROUND: The EPH family is the largest subfamily of receptor protein-tyrosine
      kinases, consisting of EPHA and EPHB subgroups. Ligands of EPH family receptors
      are called ephrins, which include ephrin-A and ephrin-B subgroups. We recently
      found that transcripts encoding the EPHB subgroup (EPHB) and the ephrin-B
      subgroup (EFNB) were expressed together in neuroblastoma (NB) cell lines.
      PROCEDURE: In this study, we examined the expression of EPHB and EFNB transcripts
      in 24 NB specimens representing all clinical stages. We found that several EPHB
      and EFNB transcripts were expressed together in all NBs examined. RESULTS: Among
      the transcripts examined, EPHB6 expression was most significantly associated with
      low stage tumors (stages 1, 2, and 4S; P = 0.0048). TrkA expression was
      significantly correlated with EPHB6, EFNB2, and EFNB3 expression (P < 0.01 in
      each case). Taken together, these data indicate that the expression of EPHB6,
      EFNB2, and EFNB3 may serve as prognostic indicators of favorable NBs. In the low
      stage NBs without MYCN amplification, EPHB2 expression was correlated both with
      MYCN expression and with TrkA expression (P < 0.01 in each case). Moreover, MYCN
      expression was correlated with TrkA expression (P < 0.01) in the low-stage NBs.
      CONCLUSIONS: This observation points to the possibility that MYCN expression
      might contribute to favorable outcome of low-stage NBs.

PMID- 11464912
TI  - Prognostic significance of DNA di-tetraploidy in neuroblastoma.
AB  - BACKGROUND: Identification of biological factors may provide tools to
      discriminate poor risk neuroblastoma patients of diagnosis, to ultimately offer
      risk adapted treatment intensity. PROCEDURES: Tumour cell DNA content, MYCN
      amplification (NMA), deletion of the short arm of chromosome 1 (del 1p) as well
      as three serological markers were assessed in 179 children with neuroblastoma.
      RESULTS: Localised regional disease (stage 1 to 3) was diagnosed in 98 patients,
      and disseminated disease in 81 patients (65 with stage 4, 16 with stage 4s).
      Median age at diagnosis was 12 months and the median observation time 4 years.
      Sixty-seven of 179 patients had near di-tetraploid tumours (37%), with a
      significantly worse prognosis of 44% overall survival at 4 years in comparison
      with 88% in near triploid tumours (P < .001). The near di-tetraploid group showed
      a significant correlation with additional adverse biological factors (NMA, del
      1p: P < 0.001), age over 1 year (P< 0.001), clinical stage 4 (P< 0.001), elevated
      ferritin (P = 0.023), and elevated LDH (P< 0.001). Multivariate analysis based on
      the overall (OS) and event free survival (EFS) estimations revealed that near di
      tetraploidy was the most powerful biological factor, with a P-value of <0.001 for
      EFS and OS, followed by NMA (P = 0.015) for OS and del 1p (P= 0.047) for EFS.
      CONCLUSIONS: This analysis underlines the important influence of near di
      tetraploidy on prognosis, and suggests that more efforts should be undertaken to
      implement this factor in future studies.

PMID- 11464913
TI  - DR-nm23 expression affects neuroblastoma cell differentiation, integrin
      expression, and adhesion characteristics.
AB  - BACKGROUND AND PROCEDURE: Nm23 gene family has been associated with metastasis
      suppression and differentiation. We studied DR-nm23 during neuroblastoma cells
      differentiation. DR-nm23 expression increased after retinoic acid induction of
      differentiation in human cell lines SK-N-SH and LAN-5. RESULTS: In several cell
      lines, overexpression of DR-nm23 was associated with more differentiated
      phenotypes. SK-N-SH cells increased vimentin expression, increased deposition of
      collagen type IV, modulated integrin expression, and underwent growth arrest; the
      murine neuroblastoma cell line N1E-115 showed neurite outgrowth and a striking
      enhancement of beta1 integrin expression. Up-regulation of beta1 integrin was
      specifically responsible for the increase in the adhesion to collagen type I
      coated plates. Finally, cells overexpressing DR-nm23 were unable to growth in
      soft agar. CONCLUSIONS: In conclusion, DR-nm23 expression is directly involved in
      differentiation of neuroblastoma cells, and its ability to affects the adhesion
      to extracellular substrates and to inhibit growth in soft agar suggests an
      involvement in the metastatic potential of neuroblastoma.

PMID- 11464914
TI  - Increased expression of p27Kip1 arrests neuroblastoma cell growth.
AB  - BACKGROUND AND PROCEDURE: To investigate the molecular mechanisms by which
      retinoic acid (RA) alters cell growth, the expression and activity of components
      of the cell cycle machinery were analyzed. RESULTS AND CONCLUSIONS: Within 2 days
      of RA treatment, and prior to the arrest of NB cells in the G1 phase of the cell
      cycle, there was a complete downregulation of GI cyclin/cdk activities. Protein
      levels for the G1 cyclin/cdk were essentially unchanged during this time,
      although there was a decrease in the steady state levels of hyperphosphorylated
      Rb and p60N-MYC proteins. The cdk inhibitors, p21Cip1 and p27Kip1 were
      constitutively expressed in KCNR, while p15 INK4B and p16 INK4A mRNA were
      undetected. Within 24 hr of RA treatment, there was a 4-fold increase in the
      expression of p27Kip1, although p27 mRNA levels were unchanged. Levels of p21Cip1
      were unaltered. Coincident with the decrease in kinase activity there was an
      increase in p27 bound to G1 cyclin/cdk. The increase in p27 was not due to an
      increase in transcription. In other cell systems, increased expression of c-MYC
      has been shown to lead to a decrease in p27 levels that is regulated at the post
      transcriptional level (sequestration). To determine whether increased levels of N
      MYC could affect the level of p27, we evaluated the expression of p27 in a series
      of N-MYC transfected cells and found that constitutive overexpression of N-MYC
      led to a decrease in the steady-state levels of p27 and in p27 bound to G1
      cyclin/cdk complexes. Using adenoviral vectors expressing p27, we found that
      infection leads to increased p27 expression, which causes a decrease in cdk
      activity and an accumulation of cells in G1.

PMID- 11464915
TI  - Universal TA cloning.
AB  - TA cloning is one of the simplest and most efficient methods for the cloning of
      PCR products. The procedure exploits the terminal transferase activity of certain
      thermophilic DNA polymerases, including Thermus aquaticus (Taq) polymerase. Taq
      polymerase has non-template dependent activity which preferentially adds a single
      adenosine to the 3'-ends of a double stranded DNA molecule, and thus most of the
      molecules PCR amplified by Taq polymerase possess single 3'-A overhangs. The use
      of a linearized "T-vector" which has single 3'-T overhangs on both ends allows
      direct, high-efficiency cloning of PCR products, facilitated by complementarity
      between the PCR product 3'-A overhangs and vector 3'-T overhangs. The TA cloning
      method can be easily modified so that the same T-vector can be used to clone any
      double-stranded DNA fragment, including PCR products amplified by any DNA
      polymerase, as well as all blunt- and sticky-ended DNA species. This technique is
      especially useful when compatible restriction sites are not available for the
      subcloning of DNA fragments from one vector to another. Directional cloning is
      made possible by appropriate hemi-phosphorylation of both the T-vectors and the
      inserts. With a single T-vector at hand, any DNA fragment can be cloned without
      compromising the cloning efficiency. The universal TA cloning method is thus both
      convenient and labor-saving.

PMID- 11464916
TI  - Lactic acid bacteria as live vaccines.
AB  - Mucosal routes for vaccine delivery offer several advantages over systemic
      inoculation from both immunological and practical points of view. The development
      of efficient mucosal vaccines therefore represents a top prority in modern
      vaccinology. One way to deliver protective antigens at the mucosal surfaces is to
      use live bacterial vectors. Until recently most of these were derived from
      attenuated pathogenic microorganisms. As an alternative to this strategy, non
      pathogenic food grade bacteria such as lactic acid bacteria (LAB) are being
      tested for their efficacy as live antigen carriers. The LABVAC european research
      network is presently comparing the vaccine potential of Lactococcus lactis,
      Streptococcus gordonii and Lactobacillus spp. To date, it has been shown that
      systemic and mucosal antigen-specific immune responses can be elicited in mice
      through the nasal route using the three LAB systems under study. Data on
      successful oral and vaginal immunisations are also accumulating for L. lactis and
      S. gordonii, respectively. Moreover, the immune responses can be potentiated by
      co-expression of interleukins. Future areas of research include improvement of
      local immunisation efficiency, analysis of in vivo antigen production,
      unravelling of the Lactobacillus colonisation mechanisms and construction of
      biologically contained strains.

PMID- 11464917
TI  - PCR clamping.
AB  - An efficient, PCR based method for the selective amplification of DNA target
      sequences that differs by a single base pair is described. The method utilises
      the high affinity and specificity of PNA for their complementary nucleic acids
      and that PNA cannot function as primers for DNA polymerases.

PMID- 11464918
TI  - Duplex DNA capture.
AB  - This article describes the sequence-specific isolation and purification of intact
      double-stranded DNA (dsDNA) by oligonucleotide/PNA-assisted affinity capture
      (OPAC). The OPAC assay is based on selective tagging of a DNA duplex by
      biotinylated oligodeoxyribonucleotide (ODN) through formation of a so-called PD
      loop. The PD-loop is assembled with the aid of a pair of PNA "openers", which
      allow sequence-specific targeting with a Watson-Crick complementary ODN probe in
      the exposed region of the dsDNA. The protocol involves three steps. First, two
      cationic bis-PNAs locally pry the DNA duplex apart at a predetermined site. Then,
      the exposed DNA single strand is targeted by a complementary biotinylated ODN to
      selectively form a stable PD-loop complex. Finally, the capture of dsDNA is
      performed using streptavidin covered magnetic beads. The OPAC procedure has many
      advantages in the isolation of highly purified native DNA over other affinity
      capture and amplification techniques.

PMID- 11464919
TI  - In vitro selection of functional nucleic acid sequences.
AB  - The power of in vitro selection methods for the isolation of nucleic acids that
      display a desired property derives from the enormous number of sequence variants
      that can be surveyed with relative ease using controlled in vitro biochemistry.
      This methodology has found a variety of applications, ranging from the study of
      nucleic acid-protein interactions and natural ribozymes to the isolation of
      nucleic acids with potential as diagnostic or therapeutic reagents or with new
      catalytic activities. The number of reported applications is growing
      exponentially, and each application presents new variables and challenges. The
      goal of this article is to guide prospective users through the myriad decisions
      that must be made in the design and execution of a successful in vitro selection
      experiment.

PMID- 11464920
TI  - Risk factors in the early diagnosis of ALS: European epidemiological studies.
AB  - Significant changes in the epidemiology of amyotrophic lateral sclerosis (ALS)
      have been observed over the last few years. Based on reports of studies from the
      1970s and early 1980s, the incidence of ALS in Europe has been considered to be
      constant, with only slight differences in the incidence of ALS between different
      countries. However, flaws in the methodologies of these studies, such as case
      definition, case ascertainment, selection bias, study design and difficulties in
      the early diagnosis of cases, have been identified. More recent studies reveal a
      trend towards an increase in the ALS mortality rate over the past two decades,
      but the significance of this trend remains unclear. Recent ALS incidence studies,
      particularly those based on the 'register model', have given new insight into ALS
      epidemiology. ALS seems to be a uniform problem across Europe, with age-specific
      incidence rates showing a progressive increase up to the 70-79 age group. False
      negative cases are frequent, ranging from 26-42% of cases. The rate of false
      positive cases is approximately 10%. In approximately half of the false-positive
      cases, the possible diagnosis of ALS was withdrawn because the initial symptoms
      did not progress. No consistent epidemiological clues concerning the cause of ALS
      have been found in epidemiological studies. The only possible associations that
      perhaps warrant further investigation include farming, mechanical and electrical
      traumas, heavy labour and toxins or chemicals.

PMID- 11464921
TI  - Risk factors in the early diagnosis of ALS: North American epidemiological
      studies. ALS CARE Study Group.
AB  - Patient-specific (endogenous) and population-specific (exogenous) risk factor
      analysis is identifying novel physical and chemical exposures which might be time
      linked to the development of amyotrophic lateral sclerosis (ALS) and other motor
      neuron diseases. Electric injury in a number of case-control studies as well as
      prolonged exposure at work and home to agricultural chemicals in pesticides and
      herbicides have been identified as significant risk factors. Heavy exercise,
      trauma with or without bone fractures and heavy metal exposure at work have not
      been confirmed as risk factors. Surprisingly, occupation as a pilot or navigator
      has recently been identified as a potential risk factor, which will need to be
      confirmed. The introduction of international patient registries in North America
      (ALS CARE) and in Europe (ALS HPS) will facilitate future studies on the
      prognosis of ALS, adherence to standards of practice, quality of life and patient
      outcome studies. An initial survey of the ALS Patient Care Database in January
      1999, when nearly 1800 patients had been entered across North America, indicated
      the median time from ALS onset to diagnosis is 14 months when no second opinion
      is requested, 12 months if the patient requests a second opinion and 10 months
      when the neurologist requests an additional opinion. No significant difference
      was found in the median time to diagnose sporadic ALS patients compared with
      familial ALS patients.

PMID- 11464922
TI  - Difficulty of early diagnosis of amyotrophic lateral sclerosis: Japanese case
      studies.
AB  - An early diagnosis of amyotrophic lateral sclerosis can be difficult to establish
      in patients with atypical features such as unilateral crural amyotrophy or
      showing motor symptoms and signs of overlapping conditions like cervical
      spondylosis, unless these patients are followed over long periods of time. Here
      we describe three such cases from our hospital in Japan.

PMID- 11464923
TI  - Problems in shortening the time to confirmation of ALS diagnosis: lessons from
      the 1st Consensus Conference, Chicago, May 1998.
AB  - The 2nd Consensus Conference (Versailles) on the early diagnosis of amyotrophic
      lateral sclerosis (ALS) developed themes identified at the 1st Consensus
      Conference (Chicago) on defining optimal management in ALS. These themes included
      describing the problems and limitations in current diagnostic practices,
      identifying consequences of early diagnosis on patient management, establishing
      recommendations to help healthcare personnel achieve the early diagnosis and
      proposing solutions to facilitate early diagnosis of ALS. Lessons from the ISIS
      Survey and the 1st Consensus Conference focused on the variability of the first
      contact physician, supply factors for specialists and variability of application
      of medical techniques. The recently introduced concept of 'ALS health states or
      stages' was reviewed in terms of ongoing and potential prospective studies. The
      relative contribution of neuroimaging or clinical neurophysiological
      investigations to accelerating the diagnosis of ALS in clinical practice was
      debated. The role of a common ALS knowledge-base among patients, initial
      healthcare providers, diagnosing neurologists and confirming neurologists was
      critically appraised with regard to simplified 'ALS diagnostic algorithm', 'ten
      aphorisms in the diagnosis of ALS' and 'ALS axioms of referral'. Refining this
      ALS knowledge-base is required to identify a minimum dataset required for the
      evaluation and diagnosis of ALS.

PMID- 11464924
TI  - Genetic factors in the early diagnosis of ALS.
AB  - The frequency of familial amyotrophic lateral sclerosis (ALS) is usually reported
      as 5-10% of all ALS cases. This figure is probably an underestimate, primarily
      due to inadequate recording of family history in the patients' charts, and to the
      not infrequent occurrence of reduced disease penetrance in pedigrees with
      familial ALS. The true familial ALS frequency may be at least double this.
      Familial ALS is heterogenetic. The only known ALS-causing gene is the CuZn
      superoxide dismutase gene (CuZn-SOD). Mutations in this gene account for a fifth
      of all familial ALS cases and a few percent of apparent sporadic ALS cases.
      Genetic testing for CuZn-SOD mutations can help confirm a diagnosis of ALS,
      especially in cases with atypical features that have been reported in some cases
      with CuZn-SOD mutations. Genetic testing should only be performed after thorough
      clinical examination and in cases with a proven or uncertain family history of
      ALS. It is not warranted in cases with no proven family history for three
      generations, unless the patient shows the characteristic phenotype associated
      with recessive inheritance of the D90A CuZn-SOD mutation.

PMID- 11464925
TI  - Pathophysiological significance of fasciculations in the early diagnosis of ALS.
AB  - In amyotrophic lateral sclerosis (ALS), muscles with preserved strength can have
      fasciculation potentials (FPs) as the only abnormality. The FPs in strong muscles
      are predominantly simple and stable, and can often be recruited by a slight
      voluntary contraction. In weak and atrophic muscles, the FPs are generally
      complex and unstable, tend to have a slower firing rate and are not recruited by
      voluntary contraction. Macro-electromyography studies suggest that these FPs are
      part of a more complex motor unit, as opposed to simple FPs which can represent
      all the motor unit. FPs driven by transcranial magnetic stimulation (TMS) were
      observed in 13 ALS patients. TMS-driven fasciculations had a simple morphology
      and were stable. Complex potentials were never cortically driven. These
      observations strengthen the conviction that fasciculations in ALS can have
      different origins. Simple, stable FPs arise proximally and are probably related
      to excitotoxicity phenomena, while complex, unstable FPs are most likely to
      originate in distal axonal sprouts that are associated with the reinnervation
      process. Some ALS patients with fatigue and mild weakness can have profuse
      fasciculations at an early phase in the evolution of the disease. Patients with
      denervation localized in one region and diffuse FPs should be strongly suspected
      of having ALS. With this strategy it should be possible to shorten the diagnosis
      time.

PMID- 11464926
TI  - Neurophysiological evaluation of cortical function in the early diagnosis of ALS.
AB  - The corticomotoneuronal system is selectively vulnerable in amyotrophic lateral
      sclerosis (ALS). In the past it has been difficult to evaluate the upper motor
      neuron component of this system. Recent studies using functional imaging and
      neurophysiological methods are now available as potential surrogate markers in
      the early diagnosis of ALS. We have used peristimulus time histograms (PSTHs) to
      evaluate the integrity of the motor cortex in ALS and in particular the cortical
      colonies that synapse with single anterior horn cells. The motor cortex in ALS
      becomes hyperexcitable early in the course of the disease and this may persist
      for some time. This is reflected in the PSTH by a desynchronized, complex
      response. Evidence indicates that this prime abnormality in ALS is supraspinal in
      origin and probably due to increased repetitive firing of the corticomotoneuron.
      The hyperexcitability is likely to be due to a combination of increased
      excitation at the level of the motor cortex and decreased inhibition due to
      dysfunction of the cortical inhibitory interneurones that modulate the output of
      the corticomotoneurone.

PMID- 11464927
TI  - Fasciculations without fibrillations: the dilemma of early diagnosis.
AB  - The challenge of identifying patients at the earliest stage of disease has
      highlighted the role of subtle markers of clinical pathology.
      Electrophysiological changes usually precede evidence of clinical weakness and
      have, therefore, been implicated. Specifically, the onset of fasciculations,
      particularly those widespread in distribution, in the absence of fibrillation
      potentials, have been suggested as an early indicator of motor neuron disease.
      Several cases will be presented here to highlight instances where diffuse
      fasciculations were not enough to accurately implicate the current diagnostic
      criteria for amyotrophic lateral sclerosis (ALS). In two instances, alternative
      diagnoses were eventually supported. If the purpose of early diagnosis is to lead
      to early treatment with experimental therapy, we must be certain that we study as
      homogenous a population of patients as possible. Fasciculations by themselves are
      not enough to implicate early diagnosis; disease progression is probably the
      single most important historical characteristic for diagnosis. Signs of active
      denervation (i.e. fibrillation potentials) are critical. Chronic weakness should
      be proportional to either atrophy or upper motor neuron signs in the affected
      muscle. This should be true for both early and late recognition of the disease.

PMID- 11464928
TI  - ALS diagnostic criteria of El Escorial Revisited: do they meet the needs of
      clinicians as well as researchers?
AB  - The El Escorial criteria for diagnosis of amyotrophic lateral sclerosis (ALS)
      have been in use for almost a decade. A revised set of criteria, meant to
      supersede the original set, was developed at a 1998 World Federation of Neurology
      (WFN) ALS meeting at Airlie House in Warrenton, Virginia, USA. This revised
      document, nicknamed El Escorial Revisited, has been published on the WFN-ALS
      website. El Escorial has proven useful in standardizing diagnostic criteria for
      entry into research trials and it is expected that El Escorial Revisited will
      help to liberalize such entry requirements. However, general neurologists and
      neuromuscular clinicians have found El Escorial to be unwieldy and generally
      unhelpful in achieving an earlier, accurate diagnosis of ALS. The El Escorial
      Revisited document is a step toward lessening these problems, but more 'user
      friendly' criteria may be necessary for clinicians and those not conducting
      research. Such ALS criteria would improve categorization of ALS patients, would
      allow clinicians more latitude in beginning ALS treatment, and would educate
      practitioners to differentiate ALS from other motor neuron and non-motor neuron
      diseases. Intensive education of physicians will help improve earlier patient
      referral and accurate ALS diagnosis. There remains a group of 'difficult cases'
      that will continue to challenge the neuromuscular specialist. Earlier diagnosis
      in this latter group will require significant advances in the fields of
      electrodiagnosis, neuroimaging, immunobiochemistry, and neurogenetics.

PMID- 11464929
TI  - Confounding effects of mimicking disorders in the early diagnosis of amyotrophic
      lateral sclerosis.
AB  - A diagnosis of amyotrophic lateral sclerosis (ALS) should be given to the patient
      only when the doctor or the neurologist feels confident or certain about the
      diagnosis. Certainty of a diagnosis of ALS is important because there are a
      number of disorders that could mimic the symptoms of ALS but differ in prognosis
      and treatment. Early treatment of ALS is critical to offer optimal therapy to the
      patient. However, ALS is difficult to diagnose at an early stage. The fact that
      ALS is a rare disease means doctors and neurologists do not always have the
      necessary experience to diagnose confidently. Therefore, clear strategies
      involving criteria for clinical evaluation and ancillary tests such as
      electromyography, muscle biopsy and magnetic resonance imaging, must be set up to
      establish the presence of upper and lower motor neuron abnormalities.

PMID- 11464930
TI  - Shortening the time to the diagnosis of amyotrophic lateral sclerosis: role of
      the neurologist.
AB  - Early diagnosis is particularly relevant in the diagnosis of amyotrophic lateral
      sclerosis (ALS) as new therapies, which may have a direct impact on the outcome
      of the disease, are being developed. Many ALS patients go to non-neurological
      specialists rather than neurologists for their first consultation. Neurologists
      specialized in the field of neuromuscular diseases therefore have a duty to help
      general neurologists and other non-neurological specialists to recognize the
      disease. This may be achieved by disseminating the El Escorial/Airlie House
      clinical and electrophysiological criteria for the diagnosis of ALS as well as by
      emphasizing that ALS is a manageable condition. Neurologists should collaborate
      better with patient organizations as well as reinforce public awareness of ALS.

PMID- 11464931
TI  - Shortening the time to diagnosis in ALS: the role of electrodiagnostic studies.
AB  - The early diagnosis of ALS has become an issue in management of the disease with
      the introduction of a therapy. As more effective treatment becomes available
      early diagnosis will become increasingly important. Electromyography (EMG) has
      potential value in this area, but will need to be applied not only with
      conventional methods but also quantitatively in order to refine the accuracy of
      diagnosis itself, and to evaluate progression. If a treatment is effective then
      progression will not occur and one of the major cornerstones of current diagnosis
      will disappear. For early diagnosis much will depend on appropriate recognition
      of the possibility of amyotrophic lateral sclerosis by primary care physicians,
      and other specialists. A semi-quantitative evaluation, utilizing clinical and EMG
      assessments, would help in this appraisal.

PMID- 11464932
TI  - Effects of the early diagnosis of amyotrophic lateral sclerosis on the patient:
      advantages.
AB  - Advantages of early diagnoses in amyotrophic lateral sclerosis include validation
      of symptoms, avoidance of unnecessary procedures, enhanced preparation for
      disability and medical education. Most importantly, earlier in the course of the
      disease--while there is a greater motor neuron pool survival--diagnosis would
      enable earlier treatment intervention.

PMID- 11464933
TI  - Effects of the early diagnosis of amyotrophic lateral sclerosis on the patient:
      disadvantages.
AB  - While the early diagnosis of disease is generally desirable, this is not always
      so. There is reason to be concerned about the reliability of clinical diagnosis
      of amyotrophic lateral sclerosis (ALS), based on currently available methods,
      early in the disease process. Applying the standard of cost-effectiveness it is
      possible to estimate the effort required to extend the lifespan of persons who
      are detected through a screening programme. Until it is possible to alter the
      treatment outcome, patients have little to gain by the early detection of ALS.

PMID- 11464934
TI  - Versailles minimal dataset for diagnosis of ALS: a distillate of the 2nd
      Consensus Conference on accelerating the diagnosis of ALS. Versailles 2nd
      Consensus Conference participants.
AB  - The 2nd Consensus Conference (Versailles) recommended that an ALS knowledge-base
      for initial healthcare providers, diagnosing neurologists and confirming
      neurologists should be defined to include a simplified version of diagnostic
      criteria less formal than the World Federation of Neurology El Escorial Revisted
      Criteria ('ALS diagnosis - An algorithm'), a set of rules concerning red flags
      which should increase the suspicion of ALS as the diagnosis and minimize the time
      between suspicion and referral for confirmation of diagnosis ('ALS axioms of
      referral'), as well as a site of symptom onset-specific checklist of minimal
      clinical examination, neuroimaging, electrodiagnostic, pulmonary function and
      laboratory test information required to confirm the diagnosis of ALS ('Versailles
      minimal dataset'). Although introductory discussions addressed the advantages and
      disadvantages of earlier diagnosis, false-positive or false-negative diagnosis,
      the frequency of follow-up and what potential biological markers to be followed,
      these issues will have to be further evaluated at future consensus conferences.

PMID- 11464935
TI  - Update on ISI survey: Europe, North America and South America.
AB  - It is well known that the diagnostic process in amyotrophic lateral sclerosis
      (ALS) may be excessively prolonged, with negative consequences for the patients
      and their families. The ISIS study assessed the diagnostic process in 201
      patients affected by ALS from 6 different countries (Argentina, Brazil, Germany,
      Italy, Spain and USA). The median time from onset to diagnosis ranged from 12
      months in Spain to 17 months in Italy. The median time for patients to have a
      first consultation with a physician was 2 months (range: 1-1.5 months) and with a
      neurologist was 6-9 months. The median time needed for the neurologist to confirm
      the diagnosis was 3-6 months. Electromyography was performed on more than 90% of
      patients in all countries, and was requested in most cases by the neurologist.
      False-negative diagnoses were quite frequent (45% of cases with at least one
      other diagnosis evoked at any time before the ALS diagnosis) and were made by
      neurologists in 28% of cases, by general practitioners in 29% of cases, by
      orthopaedic surgeons in 26% of cases and by other specialists in 18% of cases.
      The reasons for misdiagnoses were: presence of other diseases to which the
      symptomatology was attributed, misinterpretation of examinations, and lack of
      familiarity with ALS.

PMID- 11464936
TI  - Positron emission tomography (PET)--its potential to provide surrogate markers in
      ALS.
AB  - Positron emission tomography (PET) has enabled us to study the human brain with
      unrivalled sensitivity, and has already established its place in the research of
      neurological conditions such as Parkinson's disease and epilepsy. PET has been
      used as a tool in the study of patients with motor neuron disease (MND) for well
      over ten years now, but its potential in diagnosis and to identify surrogate
      markers of disease expression (phenotype) and progression has yet to be fully
      realized. The early studies using 2-18fluoro-2-deoxy-D-glucose to measure
      regional changes in cerebral metabolic rate for glucose gave the first clues to
      the more widespread involvement of the brain in MND. Later studies exploited the
      development of activation studies using 15O-containing tracers, which allowed
      correlation with neuropsychological measures, and the refinement of mapping
      techniques to delineate the extra-motor areas involved in the disease process.
      More recently, studies involving ligands such as 11C-flumazenil have allowed the
      exploration of functional reorganisation in MND, and inhibitory interneuronal
      pathways which may be crucial in modulation of disease expression. In the future
      new ligands will be applied in combination with other modalities of investigation
      (multimodal magnetic resonance imaging; neurophysiological studies) in order to
      understand the pathophysiology of this heterogeneous condition. Although the
      potential of PET has not yet been realized in ALS, it is likely to play a part in
      defining new diagnostic and surrogate markers of disease extent and severity.

PMID- 11464937
TI  - Functional magnetic resonance imaging (fMRI) clinical studies in ALS--paradigms,
      problems and promises.
AB  - Functional magnetic resonance imaging (fMRI) provides high-resolution, non
      invasive estimates of neural activity detected by a blood oxygen level dependent
      signal by assessing the increase in blood flow to the local vasculature that
      accompanies neural activity in the brain. fMRI studies with standard hand motor
      test (index-thumb opposition, ITO, or pinch) in ALS patients show good test
      retest reliability and similar amplitude of signals in ALS patients compared with
      control subjects. Isometric force can be performed with careful control for the
      force exerted, recruitment of other muscles and motion artefact. The volume
      (number of voxels above threshold) of sensorimotor and cerebellar cortex
      activated by ITO is reproducibly larger in ALS patients compared with control
      subjects. Imagined movements in ALS have been studied, as in amputees, and larger
      volumes are activated in ALS patients with imagined movements as well, compared
      with control subjects. fMRI studies in ALS patients evaluating cortical
      activation during pure somatosensory stimulation cutaneous stimulation of the
      hand to elicit the palmomental response and cutaneous stimulation of the sole to
      elicit the plantar response - indicate that ALS patients activate a significantly
      smaller volume of the contralateral sensorimotor cortex compared to control
      subjects. No statistically significant difference was seen in other areas,
      including the ipsilateral cerebellum and the contralateral thalamus. An anterior
      shift in the volume of cortex activated by these paradigms occurs in ALS
      patients, with a volume of activation, anteriorly, not activated in control
      subjects. fMRI studies will complement other clinical neurophysiological and
      neuroimaging techniques in our future attempts to solve the riddle of ALS and
      other motor neuron diseases.

PMID- 11464938
TI  - A concise overview of recent breakthroughs in imaging of ALS.
AB  - Numerous attempts have been made to visualize the motor cortex and pyramidal
      tract lesions in patients with ALS using magnetic resonance imaging (MRI), single
      photon emission computed tomography (SPECT) and positron emission tomography
      (PET). This paper briefly reviews the applicability of these imaging modalities
      in ALS.

PMID- 11464939
TI  - The role of electromyography (EMG) in the diagnosis of ALS.
AB  - Electromyography (EMG) plays a key role in the diagnostic evaluation of ALS. This
      paper deals with the contribution of conventional needle EMG and
      electroneurography to the neurophysiological assessment of ALS. In addition,
      special EMG techniques such as single fibre EMG and macro EMG are discussed as
      they mirror the decline of the number of motor units during the disease process
      and the remodelling capacity of the surviving motor units.

PMID- 11464940
TI  - Motor unit number estimation (MUNE): how may it contribute to the diagnosis of
      ALS?
AB  - Motor unit number estimation (MUNE) is a type of electrophysiological technique
      that measures the approximate number of lower motor neurons (LMNs) innervating a
      single muscle or a small group of muscles. Low MUNE counts provide evidence of
      LMN degeneration, but a single MUNE study does not determine if this loss is
      ongoing, recent or remote in time. Sequential change of MUNE count provides
      evidence for ongoing degeneration. Furthermore, sequential change in MUNE from a
      normal to abnormally low count provides evidence for progressive spread of signs
      within a region or to another region. MUNE has no established ability to identify
      other diseases that may provide a non-ALS explanation for the signs of LMN
      degeneration. If MUNE studies were to be incorporated into a future revision of
      the diagnostic criteria for ALS, prospective studies will be important to define
      more clearly the sensitivity and specificity of MUNE in patients with ALS and in
      patients with weakness that does not involve LMN degeneration. In addition to its
      potential contributions toward the diagnosis of ALS, MUNE may have greater
      potential in quantifying the rate of progression in studies of the natural
      history of ALS and the response to experimental treatment.

PMID- 11464941
TI  - Transcranial magnetic stimulation (TMS): compared sensitivity of different motor
      response parameters in ALS.
AB  - Owing to the low sensitivity of clinical signs in assessing upper motor neuron
      (UMN) involvement in ALS, there is a need for investigative tools capable of
      detecting abnormal function of the pyramidal tract. Transcranial magnetic
      stimulation (TMS) may contribute to the diagnosis by reflecting a UMN dysfunction
      that is not clinically detectable. Several parameters for the motor responses to
      TMS can be evaluated with different levels of significance in healthy subjects
      compared with ALS patients. The central motor conduction time, however, is not
      sensitive in detecting subclinical UMN defects in individual ALS patients. The
      amplitude of the motor evoked potential (MEP), expressed as the percentage of the
      maximum wave, also has a low sensitivity. In some cases, the corticomotor
      threshold is decreased early in the disease course as a result of corticomotor
      neuron hyperexcitability induced by glutamate. Later, the threshold increases,
      indicating a loss of UMN. In our experience, a decreased silent period duration
      appears to be the most sensitive parameter when using motor TMS in ALS. TMS is
      also a sensitive technique for investigating the corticobulbar tract, which is
      difficult to study by other methods. TMS is a widely available, painless and safe
      technique with a good sensitivity that can visualize both corticospinal and
      corticobulbar tract abnormalities. The sensitivity can be improved further by
      taking into account the several MEP parameters, including latency and cortical
      silent period decreased duration.

PMID- 11464942
TI  - Peristimulus time histograms (PSTHs)--a marker for upper motor neuron involvement
      in ALS?
AB  - Upper motor neuron involvement in ALS has been widely studied by means of
      transcranial magnetic stimulation and various imaging methods, such as magnetic
      resonance imaging, proton emission tomography, single photon emission computer
      tomography and magnetic resonance spectroscopy. Although almost all of these
      methods have detected 'abnormalities' of the motor cortex, no method has yet
      proven to be capable of monitoring disease progression. We and others have used
      peristimulus time histograms (PSTH) to evaluate corticomotoneuronal dysfunction.
      The primary peak (PP) in the PSTH reflects the initial rising phase of the
      excitatory post-synaptic potential evoked at the anterior horn cell by converging
      corticomotoneurons. In ALS, the PP is delayed in onset, increased in duration,
      and desynchronized. These abnormalities become more pronounced over time. Delayed
      PPs also occur more frequently in non-hereditary ALS (nHALS) with disease
      progression and are a hallmark of the autosomal recessively inherited D90A Cu-Zn
      SOD mutation. Evidence indicates that in this particular mutation, as well as in
      nHALS, the fast-conducting monosynaptic pathway originating from large pyramidal
      Betz cells is preferentially lost, whereas a slow-conducting pathway seems to be
      spared. This is most likely due to the enormous metabolic demand of the large
      pyramidal cells, which may explain the selective vulnerability of the most recent
      phylogenetic system to develop in the human nervous system.

PMID- 11464943
TI  - Genetic markers of ALS.
AB  - As a result of the advances made in the field of molecular and population
      genetics, it is anticipated that several genes underlying ALS or predisposing to
      ALS might be identified in the near future. This will enable physicians to
      establish a diagnosis of ALS based on molecular findings in addition to clinical
      and electrophysiological findings. At present, mutations in the gene encoding for
      the free radical scavenging enzyme, superoxide dismutase (SOD1), is the only
      basis for a molecular diagnosis. Other mutations are under investigation and
      confirmed results are eagerly awaited.

PMID- 11464944
TI  - Serum and cerebrospinal fluid biochemical markers of ALS.
AB  - To date there is no satisfactory serum or cerebrospinal fluid (CSF) metabolic
      marker with which to identify patients with ALS. The goal of finding a suitable
      marker will be more feasible following the identification of defined subgroups of
      patients with ALS. Some aspects of neurotransmitter chemistry in CSF seem worthy
      of further investigation, in particular, clarification of whether there is a
      significant elevation of CSF glutamate in a subgroup of patients and whether
      there are robust alterations in the noradrenaline transmitter system. It seems
      unlikely, in the face of present evidence, that the presence of aberrant
      exitatory amino acid transporter 2 transcripts in CSF will prove to be a useful
      marker of ALS. Increased levels of 3-nitrotyrosine and neurofilament light in
      CSF, while not entirely disease-specific for ALS, may nevertheless prove useful
      confirmatory markers of the disease and its progression.

PMID- 11464945
TI  - Proton magnetic resonance spectroscopy (1H-MRS) in ALS.
AB  - Establishing the presence of upper motor neuron (UMN) pathology is essential for
      an accurate and definite diagnosis of ALS. However, clinical identification of
      UMN dysfunction can be difficult in early disease or if lower motor neuron signs
      are prominent. A routine technique such as magnetic resonance imaging is usually
      normal and non-specific. Proton magnetic resonance spectroscopy (1H-MRS) is a non
      invasive neuroimaging technique that has successfully demonstrated evidence of
      neuronal abnormalities in motor regions of the brain in ALS. This review
      discusses the advantages and limitations of employing 1H-MRS as an investigative
      tool in the diagnosis of ALS.

PMID- 11464946
TI  - Role of mitochondria in ALS.

PMID- 11464947
TI  - The skin in ALS.

PMID- 11464948
TI  - Intrathecal delivery of BDNF.

PMID- 11464949
TI  - Superoxide dismutase-1 mutation-related neurotoxicity in familial amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      characterized by motor neuron system involvement, and is epidemiologically
      subclassified into sporadic, familial and endemic forms. About 20% of ALS
      families are associated with mutations in the gene for superoxide dismutase-1
      (SOD1) encoded on chromosome 21q22.1. Several studies have pointed to a variety
      of functions of mutant SOD1, which has enhanced catalytic activity of the
      peroxynitrite-mediated tyrosine nitration, readily releases the reactive Cu ions,
      induces apoptotic cell death, has enhanced peroxidase activity, damages the
      mitochondria to release Ca2+, and forms SOD1-containing aggregates in the
      cytoplasm. Many of these studies have obtained evidence for increased oxidative
      damage in ALS. On the other hand, some reports disagree with oxidative damage
      involvement in SOD1 mutant ALS. In considering the findings of increased
      oxidative damage in mutant SOD1-expressing transgenic mice, it should be
      remembered that overexpression of mutant SOD1 may enhance oxidative stress
      generation from this enzyme. In this review, we present the clinicopathological
      features of SOD1 mutant familial ALS and its transgenic mouse model, and also
      discuss SOD1 mutation-related neurotoxicity, including SOD1 protein aggregation
      and post-translational protein modification.

PMID- 11464950
TI  - New consensus research on neuropathological aspects of familial amyotrophic
      lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: inclusions
      containing SOD1 in neurons and astrocytes.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      that primarily involves the motor neuron system. Approximately 5-10% of ALS is
      familial. Superoxide dismutase 1 (SOD1) gene mutations are shown to be associated
      with about 20% of familial ALS (FALS) patients. The neuronal Lewy-body-like
      hyaline inclusion (LBHI) and astrocytic hyaline inclusion (Ast-HI) are
      morphological hallmarks of certain SOD1-linked FALS patients with SOD1 gene
      mutant and transgenic mice expressing human SOD1 with G85R mutation. From the
      detailed immunohistochemical analyses, the essential common protein of both
      inclusions is SOD1. Ultrastructurally, both inclusions consist of granule-coated
      fibrils 15-25 nm in diameter. Based on the immuno-electron microscopical finding
      that these abnormal granule-coated fibrils are positive for SOD1, the formation
      (or aggregation) of the abnormal fibrils containing SOD1 would be essential
      evidence in diseases caused by various SOD1 mutations. The granule-coated fibrils
      are also modified by advanced glycation end products (AGEs). The AGEs themselves
      are insoluble molecules with direct toxic effects on cells. AGE formation of SOD1
      composing the granule-coated fibrils (probable AGE-modified mutant SOD1) may
      amplify their aggregation and produce a more marked toxicity.

PMID- 11464951
TI  - Role of mitochondria in amyotrophic lateral sclerosis.
AB  - Neurodegeneration in amyotrophic lateral sclerosis (ALS) is characterized by the
      specific loss of central and peripheral motor neurons. While this pattern of
      neuronal demise gives rise to a distinct clinical syndrome, at the cellular and
      molecular level ALS pathology is similar to that seen in other neurodegenerative
      diseases. In particular, mitochondrial dysfunction in ALS is reminiscent of that
      observed in Alzheimer's and Parkinson's diseases. Mitochondria in persons with
      ALS demonstrate impaired electron transport, increased free radical generation,
      and an inability to adequately buffer cytosolic calcium shifts. These
      abnormalities are probably systemic and potentially due to mutation of
      mitochondrial DNA.

PMID- 11464952
TI  - The skin in amyotrophic lateral sclerosis.
AB  - It has been repeatedly noted, but never as yet fully explained, that patients
      with ALS do not develop bedsores even at the terminal stage. Furthermore, the
      skin of ALS patients feels supple, like tanned leather, and loses elasticity.
      When the skin is stretched, it returns only sluggishly to its original position.
      We termed this property of skin 'delayed return phenomenon (DRP)'; it is usually
      seen more than 2 1/2 years after the onset of symptoms. Though it is thought that
      phenomena such as DRP and the absence of bedsores are characteristic of this
      disease, little attention has been paid to these unique features in ALS patients.
      In this review we summarize recent developments in research on skin from ALS
      patients, which may give insight into the possible mechanisms and pathogenesis
      underlying this disorder.

PMID- 11464953
TI  - A phase I/II trial of recombinant methionyl human brain derived neurotrophic
      factor administered by intrathecal infusion to patients with amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Brain derived neurotrophic factor (BDNF) is a potent survival factor
      for motoneurons. This study investigated the safety and tolerability of
      recombinant methionyl human BDNF (r-metHuBDNF) infused intrathecally by means of
      an implanted pump in patients with ALS. METHODS: Twenty-five patients with
      probable or definite ALS were treated with either r-metHuBDNF (25, 60, 150, 400
      or 1000 microg/day) or placebo in a 12-week, randomized, double-blinded,
      sequential, dose-escalation study. Test treatment was interrupted by a washout
      period from days 11 to 25 to allow the evaluation of laboratory safety measures.
      In each dose cohort four patients received r-metHuBDNF and one received placebo.
      On completion of the double-blind period of the study all patients continued to
      receive r-metHuBDNF in an open-label extension for up to 60 weeks. Lumbar
      cerebrospinal fluid (CSF) samples were taken periodically from all patients for
      the measurement of r-metHuBDNF levels and in a minority of patients these were
      supplemented by cistemal samples. RESULTS: Within days after the initiation of
      infusion the majority of patients receiving r-metHuBDNF reported mild sensory
      symptoms, including paraesthesias or a sense of warmth, which were usually
      confined to the lower limbs and were frequently exacerbated by neck flexion. In
      most instances these symptoms decreased or even disappeared over several weeks.
      Sleep disturbance, dry mouth, agitation and other behavioural effects were
      encountered at higher doses (>150 microg/day) and necessitated dose reductions.
      The spinal CSF levels of r-metHuBDNF were directly related to dose, with a lumbar
      to cervical ratio of approximately 4:1. CONCLUSIONS: The intrathecal delivery of
      r-metHuBDNF in doses of up to 150 microg/day was well tolerated and appears
      feasible. The reversible CNS effects with higher dose indicate that BDNF can be
      delivered cranially against CSF flow. The small number of patients and the design
      of the study did not permit conclusions to be drawn about the efficacy of the
      treatment.

PMID- 11464954
TI  - Oral administration of creatine monohydrate retards progression of motor neuron
      disease in the wobbler mouse.
AB  - BACKGROUND AND AIMS: Creatine has a neuroprotective effect in mutant superoxide
      dismutase (G93A) transgenic mice, an animal model of motor neuron disease (MND).
      Treatment with creatine monohydrate enhances muscle strength in patients with
      neuromuscular disorders. The purpose of our study was to determine whether
      administration of creatine monohydrate can attenuate progressive disease in
      wobbler mice. METHODS: After an initial diagnosis of disease at the age of 3-4
      weeks, creatine monohydrate (5 or 50 mg/kg, po) or vehicle was given to wobbler
      mice daily for 4 weeks in a blinded fashion. We compared symptomatic and
      neuropathological assessments among the three groups. RESULTS: Creatine levels in
      biceps muscles were increased by approximately 20% following administration of
      higher-dose creatine monohydrate. In comparison with vehicle, treatment with
      higher doses of creatine monohydrate potentiated grip strength, attenuated
      forelimb contracture and increased the weight of biceps muscles. Mice treated
      with higher doses of creatine monohydrate showed retarded denervation muscle
      atrophy in the biceps muscles and reduced degeneration of the spinal motor
      neurons. Thus, oral administration of creatine monohydrate delayed the
      progression of disease in wobbler mice. CONCLUSION: Our results indicate that
      this molecule may have therapeutic potential in human motor neuropathy or MND.

PMID- 11464955
TI  - Increased serum hyaluronic acid in amyotrophic lateral sclerosis: relation to its
      skin content.
AB  - BACKGROUND: Abnormalities of hyaluronic acid (HA) of skin have been reported in
      patients with amyotrophic lateral sclerosis (ALS). However, little is known
      concerning the changes of serum HA in ALS. The purpose of this study was to
      investigate skin HA content and serum HA levels in ALS patients. METHODS: We
      measured skin HA content and serum HA levels in patients with ALS, and compared
      the results with those of control subjects. RESULTS: Skin HA content in ALS
      patients was significantly higher than in diseased control subjects and control
      subjects without neurological disorders, and increased significantly, the longer
      the duration of illness. Serum HA concentrations in patients with ALS were
      significantly higher than in diseased control subjects and in healthy control
      subjects, and were positively and significantly associated with duration of
      illness. There was an appreciable positive correlation between serum HA
      concentrations and skin HA content in ALS patients. CONCLUSION: These data
      suggest that a metabolic alteration of HA may take place in ALS and increased
      levels of serum HA may reflect an increased content of skin HA in ALS.

PMID- 11464956
TI  - Mechanisms of brain injury: L1 cell adhesion molecule as a target for ethanol
      induced prenatal brain injury.
AB  - The magnitude of the problem of neurodevelopmental disorders is enormous.
      Frequently, the mechanism of injury is unknown. In this article, the function of
      one cell adhesion molecule, L1, will be reviewed. L1 is critical for proper
      central nervous system development. Similarities between patients with fetal
      alcohol syndrome and with L1 mutations suggest that the mechanism of
      developmental neurotoxicity of ethanol is partly due to effects on L1 cell
      adhesion molecule.

PMID- 11464957
TI  - Perinatal implications of maternal hypertension.
AB  - Hypertensive disorders of pregnancy are prototypical of maternal conditions
      associated with reduced uteroplacental blood flow. Hypertensive disorders in
      pregnancy include chronic hypertension, preeclampsia-eclampsia, superimposed
      preeclampsia, and gestational hypertension. Pathophysiology of these disorders
      include deficient uterine vascular modeling in the process of placentation and
      aberrations of vasomotor regulation. Aberrations of uterine renin-angiotensin
      system may play a proximate role in the pathogenesis of preeclampsia syndrome.
      Clinical manifestations are explained in this review based on resultant
      vasoconstriction and ischemia in systemic and regional circulations. Perinatal
      implications of hypertensive disorders both in terms of early neonatal outcome
      and long-term neurodevelopmental effects are described. Methods of antenatal
      assessment of the fetus and, briefly, principles of clinical management are
      described.

PMID- 11464958
TI  - Risk factors for neurologic impairment among very low-birth-weight infants.
AB  - Although cerebral palsy is the most common neurologic impairment among very low
      birth-weight survivors, its etiology remains uncertain. Current research supports
      the role of both antenatal and neonatal factors in the pathogenesis of cerebral
      palsy among these extremely premature infants. Important antenatal risk factors
      include chorioamnionitis and multiple placental lesions. Maternal preeclampsia
      may provide neuroprotection. The major neonatal risk factors include severe
      cranial ultrasound abnormalities, chronic lung disease, hyperbilirubinemia, and
      possibly hypothyroxinemia.

PMID- 11464959
TI  - Fetal and neonatal neurologic consultations: identifying brain disorders in the
      context of fetal-maternal-placental disease.
AB  - Pediatric neurologists provide an important consultative role for the fetus or
      neonate with a suspected brain disorder. Although most consultations are
      initiated after birth, neonatal neurologic dysfunction may be reflective of fetal
      brain damage or maldevelopment. Maternal or placental/cord disease states can
      predispose the fetus or neonate to brain disorders during the antepartum,
      intrapartum, or early postpartum periods. Neurologists must therefore consider
      maternal, placental, and fetal conditions on which a neonatal encephalopathy may
      be superimposed, with or without recent brain injury. This review suggests how
      the pediatric neurologist can contribute more effectively to fetal and neonatal
      neurologic evaluations regarding etiologies and mechanisms of brain injury; their
      role will enhance diagnostic services composed of maternal-fetal specialists,
      placental and pediatric pathologists, neonatologists, neurosurgeons, geneticists,
      and other pediatric subspecialists. Selected examples of structural markers
      during fetal life, and functional markers during neonatal life, illustrate the
      wide spectrum of disease states that are highly dependent on the timing and
      location of brain injury. The pediatric neurologist has the opportunity to
      integrate these complementary lines of investigation into a responsive
      consultative opinion, which is both medically accurate and ethical, responsible
      to the welfare of the mother and child.

PMID- 11464960
TI  - Magnetic resonance techniques in the evaluation of the fetal and neonatal brain.
AB  - Magnetic resonance imaging (MRI) has contributed dramatically to our
      understanding of the newborn with neurologic problems. Recently developed
      magnetic resonance techniques, such as fetal MRI and MR spectroscopy, offer
      additional insight into normal and pathologic processes affecting the fetal and
      neonatal CNS. This article examines developmental abnormalities as reflected in
      neuroimaging studies and discusses some of the newer MR modalities and their
      capabilities.

PMID- 11464961
TI  - Genetic advances in central nervous system malformations in the fetus and
      neonate.
AB  - Malformations of the central nervous system (CNS) are commonly encountered by the
      pediatric neurologist when called to evaluate a fetus or newborn. Such
      malformations may be isolated or appear as part of a genetic syndrome. In the
      past few years there have been great advances in identifying the genes and
      genetic alterations for many isolated CNS malformations and syndromes with CNS
      malformations. Therefore, it is important to look for associated anomalies in any
      infant with a CNS malformation, as well as consideration of the rest of the
      family. We have chosen four malformations (holoprosencephaly, hydrocephalus,
      lissencephaly, and schizencephaly) to serve as a paradigm for genetic
      malformations of the CNS. Understanding the underlying genetic etiology of a
      disorder allows us to give more accurate recurrence risk counseling, to better
      estimate potential complications, and to better manage the patient's care. As
      research continues, additional malformations and syndromes will be understood on
      the genetic level, and combining this genetic information with neurologic
      understanding will translate into better medical care for the patient.

PMID- 11464962
TI  - Annotation: Recent research examining the role of peer relationships in the
      development of psychopathology.
AB  - This Annotation highlights recent research on the role of peer group and
      friendship factors in the development of psychopathology in childhood and
      adolescence. Several processes are considered. including peer rejection (e.g.,
      exclusion and victimization), social withdrawal and avoidance of peer
      interaction, and the socialization of deviant behavior and internalizing
      problems. The mediating influences of several proximal components are examined,
      including cognitive-perceptual factors and emotion regulation. In addition, the
      moderating influences of close friendship, age, gender, ethnicity, and group
      norms are considered. Several promising avenues for future directions in research
      are highlighted, including the examination of heterogeneity in developmental
      processes, further investigation of gender-based norms, and the application of
      multi-level modeling techniques and gene-environment process models.

PMID- 11464963
TI  - The long-term stability of sociometric status classification: a longitudinal
      study of included pupils who have moderate learning difficulties and their
      mainstream peers.
AB  - This study investigated the longitudinal stability of sociometric classification
      in two groups of children aged 8 to 10 years over a 2-year period. Two simple,
      but sensitive and valid forced-choice sociometric measures were completed by 41
      children with moderate learning difficulties (MLD) and 375 mainstream children.
      On both occasions and on both measures (one using a "work with" and one a "play
      with" sociometric criterion) MLD pupils were significantly less likely to be
      classified as popular and more likely to be classified as rejected. Over the 2
      year period just over half of the children, whether MLD or mainstream, were
      classified in the same sociometric category. However, the stability coefficients
      for the rejected and popular sociometric status groups were found to be higher in
      the included sample than in the mainstream sample. The results of this study are
      compared with previous longitudinal studies in the area that have focused on
      mainstream pupils, and implications for the use of sociometric measures in
      evaluating the outcomes of inclusion are discussed.

PMID- 11464964
TI  - An evaluation of nonresponse bias in peer, self, and teacher ratings of
      children's psychosocial adjustment.
AB  - The last decades have shown a rapid increase in nonresponse rates. For this
      reason it is important to study nonresponse and think about it critically. In
      this article we investigated whether nonresponse affected estimates of the levels
      of adjustment problems in children and the correlations between these outcomes.
      The nonresponse was caused by parents who refused permission to interview their
      children at school, parents who did not return a questionnaire, teachers who did
      not complete the questionnaire, and parents who refused to participate in an in
      depth study, with nonresponse rates of 9%, 69%, 25%, and 46% respectively. The
      sample consisted of 1282 children aged 4 5 years and the dependent measures were
      peer-rated sociometric status, self-rated wellbeing at school, and teacher-rated
      behaviour problems. Despite considerable nonresponse in some conditions our
      results showed hardly any evidence for bias. This suggested that bias cannot
      simply be inferred from the amount of nonresponse and that standard rules such as
      "nonresponse rates higher than 50% are not acceptable" lack a scientific basis.
      Instead, we argue that to assess nonresponse bias the specific conditions and
      analyses of the study will need to be considered and special measures may be
      required.

PMID- 11464965
TI  - Prospective 10-year follow-up in adolescent anorexia nervosa--course, outcome,
      psychiatric comorbidity, and psychosocial adaptation.
AB  - The aim of the present study was to follow up the long-term course of adolescent
      onset anorexia nervosa by repeated assessment, to analyze the association between
      the course of the eating disorder and psychiatric comorbidity, and to evaluate
      psychosocial outcome. The sample consisted of 39 inpatients who were
      reinvestigated 3, 7, and 10 years after discharge. The patients and 39 controls
      matched for age, gender, and occupational status were assessed with structured
      interviews on DSM-III-R eating disorders, additional axis I and axis II
      psychiatric disorders, and psychosocial functioning. Results showed that 69 % of
      the original subjects met the criteria for full recovery at the 10-year follow
      up. One patient (3%) still exhibited the full syndrome of restrictive anorexia
      nervosa, two patients (5%) the full syndrome of bulimia nervosa. None of the
      patients had died. Of the subjects, 51% currently had an axis I psychiatric
      disorder and 23% met the full criteria for a personality disorder. Apart from the
      eating disorder, anxiety disorders and avoidant-dependent and obsessive
      compulsive personality disorders were the most common psychiatric diagnoses.
      There was a significant association between psychiatric comorbidity and the
      outcome of the eating disorder and between outcome and psychosocial adaptation.
      With regard to psychiatric morbidity and psychosocial functioning, long-term
      recovered patients did not differ significantly from normal controls. It is
      concluded that in most patients adolescent anorexia nervosa takes a prolonged
      course, although it seems to be more favorable than in adult-onset forms. Those
      who achieve complete recovery from the eating disorder have a good chance of
      overcoming other psychiatric disorders and to adapt to social requirements.

PMID- 11464966
TI  - Ten-year follow-up of adolescent-onset anorexia nervosa: psychiatric disorders
      and overall functioning scales.
AB  - The aim of this study was to assess prospectively the long-term outcome in a
      representative sample of teenage-onset anorexia nervosa (AN) in respect of
      psychiatric disorders and overall outcome. Fifty-one AN cases, recruited by
      community screening, with a mean age of onset of 14 years, was contrasted with 51
      matched comparison cases at a mean age of 24 years (10 years after AN onset). All
      102 cases had been examined at ages 16 and 21 years. At 24 years all probands
      were interviewed regarding psychiatric disorders (SCID-I) and overall outcome
      (Morgan-Russell assessment schedule, the GAF). There were no deaths at 10-year
      follow-up. One in four in the AN group had a persisting eating disorder (ED),
      including three who still had anorexia nervosa. Lifetime diagnoses of affective
      disorders and obsessive-compulsive disorder were over-represented in the AN
      group. Outcome according to Morgan-Russell was poor in 27%, intermediate in 29%,
      and good in 43%. According to the GAF, half the AN group had a poor psychosocial
      functioning. These were subjects with either a persisting ED or lifelong problems
      with social interaction or obsessive-compulsive behaviour. Ten-year outcome of
      teenage-onset AN is favourable in the majority of cases; most individuals have
      recovered from their ED and have no other axis I disorder. However, half the AN
      group reported poor psychosocial outcome, in most cases explained by a persisting
      ED or chronic obsessive-compulsive behaviour/social interaction problems.

PMID- 11464967
TI  - Effects of maternal depression on cognitive development of children over the
      first 7 years of life.
AB  - The effects of postnatal depression on cognitive test scores at 20 months and 4;
      8 years of age as well as the timing (onset in the early postnatal period versus
      later), severity, number of episodes, duration of longest phase, recency, and
      chronicity of material depression on children's cognitive scores at 6; 3 years
      was investigated. In South Bavaria, Germany, 1,329 mothers of singletons were
      screened when the children were 6; 3 years of age for the presence of depressive
      symptoms since the birth of their infant. A standard interview (SADS-L) was used
      to ascertain DSM-IV diagnosis and details of depressive episodes. Ninety-two
      mothers were diagnosed as having suffered DSM-IV defined depression (7%). Seven
      hundred and twenty-one mothers had no depressive episodes or symptoms from their
      children's birth until 6; 3 years and were used as control group. The children
      had been assessed with the Griffiths Scales of Babies' Abilities (20 months), the
      Columbia Mental Maturity Scales (CMM) at 4; 8 years, and the Kaufman Assessment
      Battery for Children (K-ABC) at 6; 3 years. No significant main effects of
      severity, timing of onset, duration, or chronicity of depression of the child's
      cognitive development were found. Significant interactions of gender with
      chronicity of maternal depression (i.e. early-onset major and repeated episodes)
      were detected. Low SES boys or boys born at neonatal risk of mothers with chronic
      depression had lower Achievement Scores in the K-ABC at 6; 3 years than children
      of mothers with less severe depression or controls. It is concluded that maternal
      depression per se has negligible effects on children's cognitive development.
      Long-term effects may be found when maternal depression is chronic, the child is
      a boy and neonatal risk-born, or the family suffers other social risks.

PMID- 11464968
TI  - Rethinking maternal sensitivity: mothers' comments on infants' mental processes
      predict security of attachment at 12 months.
AB  - This study investigated predictors of attachment security in a play context using
      a sample of 71 mothers and their 6-month-old infants. We sought to rethink the
      concept of maternal sensitivity by focusing on mothers' ability accurately to
      read the mental states governing infant behaviour. Five categories were devised
      to assess this ability, four of which were dependent on maternal responses to
      infant behaviours, such as object-directed activity. The fifth, mothers'
      Appropriate minded-related comments, assessed individual differences in mothers'
      proclivity to comment appropriately on their infants' mental states and
      processes. Higher scores in this fifth category related to a secure attachment
      relationship at 12 months. Maternal sensitivity and Appropriate mind-related
      comments were independent predictors of attachment security at 12 months,
      respectively accounting for 6.5% and 12.7% of its variance. We suggest that these
      findings are in line with current theorising on internal working models of
      attachment, and may help to explain security-related differences in mentalising
      abilities.

PMID- 11464969
TI  - Longitudinal change in parenting associated with developmental delay and catch
      up.
AB  - The current study examined the predictors of parent-child relationship quality
      and developmental change in a sample of children adopted into the U.K. following
      severe early privation, and in a comparison sample of nondeprived, within-country
      adoptees. One hundred and fifty-eight children adopted from Romania and 52 U.K.
      adoptees were assessed at age 6 years; longitudinal data (age 4 and 6 years) were
      available on the 110 Romanian adoptees placed into U.K. homes before 24 months of
      age and all U.K. adoptees. Ratings of parent-child positivity and negativity
      during a semistructured interaction task were obtained from coders who were blind
      to the child's background. Results indicated that adoptive parent-child
      relationship quality was related to duration of deprivation and that
      cognitive/developmental delay mediated this association. The magnitude of this
      effect was modest and diminished over time. Longitudinal analyses revealed that
      positive change in parent-child relationship quality was most marked among
      children who exhibited cognitive catch-up between assessments. The direction of
      effects appeared to be primarily child to parent. The findings underscore the
      need for further research on the long-term impact of early experiences on
      psychosocial development.

PMID- 11464970
TI  - Issues in measuring quality of life in childhood cancer: measures, proxies, and
      parental mental health.
AB  - The relationship between child- and parent-reported quality of life (QOL) and the
      effects of parental mental health, illness stressors, and child vulnerability was
      explored using two measures of QOL: the Pediatric Cancer Quality Life-32 (Varni
      et al., 1998a) and the Disquol (Eiser, Cotter, Oades, Seamark, & Smith, 1999).
      Thirty-two children with acute lymphoblastic leukaemia (mean age = 8.92 years)
      and 36 parents completed measures of QOL when attending routine clinic. In
      addition, parents also completed the General Health Questionnaire (GHQ-28),
      perception of the child's vulnerability, and illness-related stressors.
      Significant correlations were found between the overall scores on the two child
      completed QOL measures, with a range of poor, moderate to good correlations found
      between the individual subscales. Poor to moderate concordance was found between
      child and parent reports. Children who self-reported poorer QOL had mothers who
      were more depressed. Parents who reported poorer QOL for their child reported
      more illness stressors and perceived their child as being more vulnerable.
      Assumptions that concordance between child and parent ratings of QOL is a
      necessary requirement for new measures of QOL are challenged.

PMID- 11464971
TI  - Body image, psychosocial functioning, and personality: how different are
      adolescents and young adults applying for plastic surgery?
AB  - This study addressed three questions: (1) Do adolescents undergoing plastic
      surgery have a realistic view of their body? (2) How urgent is the psychosocial
      need of adolescents to undergo plastic surgery? (3) Which relations exist between
      bodily attitudes and psychosocial functioning and personality? From 1995 to 1997,
      184 plastic surgical patients aged 12 to 22, and a comparison group of 684
      adolescents and young adults from the general population aged 12 to 22 years, and
      their parents, were interviewed and completed questionnaires and standardised
      rating scales. Adolescents accepted for plastic surgery had realistic appearance
      attitudes and were psychologically healthy overall. Patients were equally
      satisfied with their overall appearance as the comparison group, but more
      dissatisfied with the specific body parts concerned for operation, especially
      when undergoing corrective operations. Patients had measurable appearance-related
      psychosocial problems. Patient boys reported less self-confidence on social areas
      than all other groups. There were very few patient-comparison group differences
      in correlations between bodily and psychosocial variables, indicating that bodily
      attitudes and satisfaction are not differentially related to psychosocial
      functioning and self-perception in patients than in peers. We concluded that
      adolescents accepted for plastic surgery have considerable appearance-related
      psychosocial problems, patients in the corrective group reporting more so than in
      the reconstructive group. Plastic surgeons may assume that these adolescents in
      general have a realistic attitude towards their appearance. are psychologically
      healthy, and are mainly dissatisfied about the body parts concerned for
      operation. corrective patients more so than reconstructive patients. Introverted
      patients may need more attention from plastic surgeons during the psychosocial
      assessment.

PMID- 11464972
TI  - Preschool developmental pathways to preadolescent internalizing and externalizing
      problems.
AB  - The present study investigated longitudinal pathways from specific early
      preschool behavioral problems (ages 2-3 years) to internalizing and externalizing
      problems in preadolescence (ages 10-11 years), and the role of social problems at
      school entry (ages 4-5 years) in such pathways. Path analyses were performed
      using both parent and teacher reports in a sample of 251 to 346 children from the
      general population, depending on the availability of parent and teacher data at
      each time of assessment. Structural equation modeling revealed homotypic
      internalizing and externalizing pathways, predictions from early preschool
      externalizing problems to later internalizing problems, and negative predictive
      paths from early internalizing problems to externalizing problems in
      preadolescence. Cross-informant predictions spanning 8 years were found between
      parent-reported aggression and overactivity at ages 2-3 years and teacher
      reported externalizing problems at ages 10-11 years. Further, results showed that
      boys' pathways were more complex and showed greater predictive validity than
      pathways for girls, and that social problems at school entry played a significant
      role in pathways to internalizing problems, but only for boys. The results are
      discussed from a developmental psychopathology perspective.

PMID- 11464973
TI  - Sensitivity to reward delay in children with attention deficit hyperactivity
      disorder (ADHD).
AB  - The present study compared the sensitivity to pre- and post-reward delays of
      children with and without DSM-IV combined type ADHD. Thirty-six children with DSM
      IV combined type ADHD and 36 controls completed a signal-detection task. Correct
      identification of one stimulus produced an immediate reward and then a 3.5 s
      delay before the next trial (immediate reward). Correct identification of the
      other stimulus was associated with a 3.5 s delay before reward was delivered
      (delayed reward). Group differences emerged in response bias toward the
      immediately rewarded alternative. Children in the ADHD group showed a greater
      bias toward immediate reward than the controls. Children in the control group
      showed different patterns of response bias and discriminability following
      immediate and delayed rewards. For these children discriminability was lower and
      response bias was greater on trials following delayed reward. Both groups
      responded more slowly on trials following delayed reward. These findings support
      the hypothesis that children with ADHD are unusually sensitive to pre-reward
      delays.

PMID- 11464974
TI  - Documenting the case for stem cell transplantation: the role of evidence-based
      reviews and implications for future research. Statement of the Steering Committee
      for Evidence-Based Reviews of the American Society for Blood and Marrow
      Transplantation (ASBMT).

PMID- 11464975
TI  - The role of cytotoxic therapy with hematopoietic stem cell transplantation in the
      therapy of diffuse large cell B-cell non-Hodgkin's lymphoma: an evidence-based
      review.

PMID- 11464976
TI  - Tandem high-dose chemotherapy in high-risk primary breast cancer: a multivariate
      analysis and a matched-pair comparison with standard-dose chemotherapy.
AB  - Stem cell-supported high-dose chemotherapy (HDCT) is currently being evaluated in
      patients with high-risk primary breast cancer (HRPBC), as defined by extensive
      axillary lymph node involvement. Conclusive results from randomized studies with
      sufficient patient numbers and follow-up are pending. We retrospectively analyzed
      144 HRPBC patients enrolled in a single-arm trial of tandem HDCT at the
      University of Heidelberg to evaluate the prognostic value of nodal ratio,
      HER2/neu status, and cytokeratin-positive bone marrow cells and to compare the
      outcomes of these patients with those of a conventionally treated control group
      of 91 patients matched by nodal ratio, tumor size, combined hormone-receptor
      status, and HER2/neu status. The tandem HDCT regimen consisted of 2 cycles of
      induction chemotherapy followed by 2 cycles of blood stem cell-supported high
      dose ifosfamide, 12 g/m2; carboplatin, 900 mg/M2; and epirubicin, 180 mg/m2.
      Conventionally treated patients received a regimen containing anthracycline
      without taxanes (52 patients) or CMF (cyclophosphamide, methotrexate, and 5
      flurouracil; 39 patients). With a median follow-up of 3.8 years, disease-free,
      distant disease-free, and overall survival rates were 62%, 65%, and 84%,
      respectively. In univariate analysis, besides the hormone receptor status (P =
      .007), HER2/neu overexpression was the strongest predictor of earlier death (P =
      .017). In multivariate analysis, a nodal ratio of > or =0.8 was found to be the
      only independent predictor of relapse (relative risk [RR] = 2.09; 95% confidence
      interval [CI], 1.21-3.60; P = .008) and only the absence of hormone receptors was
      associated with earlier death (RR = 3.59; 95% CI, 1.45-8.86; P = .006). Despite a
      trend toward later distant relapse after HDCT compared with standard-dose
      chemotherapy with a median follow-up of 3 years (P = .059), thus far, matched
      pair analysis has not demonstrated significantly better survival rates after HDCT
      in all matched patients (P = .786) or in the subgroups of anthracycline-treated
      patients and patients with and without overexpression of HER2/neu. So far, the
      follow-up time has been too short to draw definite conclusions; however, patients
      with a nodal ratio of > or =0.8, receptor-negative tumors, or HER2/neu
      overexpression are at high risk for relapse and death, irrespective of the kind
      of adjuvant chemotherapy.

PMID- 11464977
TI  - Randomized, placebo-controlled, double-blind study of a cytomegalovirus-specific
      monoclonal antibody (MSL-109) for prevention of cytomegalovirus infection after
      allogeneic hematopoietic stem cell transplantation.
AB  - MSL-109 is a monoclonal antibody specific to the cytomegalovirus (CMV)
      glycoprotein H with high neutralizing capacity. In a prospective, randomized,
      double-blind study, allogeneic hematopoietic stem cell transplantation (HSCT)
      recipients with positive donor and/or recipient serology for CMV before
      transplantation received either 60 mg/kg MSL-109 (n = 59), 15 mg/kg MSL-109 (n =
      60), or placebo (n = 60) intravenously every 2 weeks from day -1 until day 84
      after transplantation. CMV pp65 antigenemia, CMV-DNA load in plasma, and viremia
      by culture were tested weekly. Primary end points were development of pp65
      antigenemia at any level and/or viremia for which ganciclovir was given. There
      was no statistically significant difference in CMV pp65 antigenemia or viremia
      among patients in the 60-mg group (pp65 antigenemia, 47%; viremia, 15%), the 15
      mg group (52%; 23%), and the placebo group (45%; 17%). There was also no
      difference in maximum levels of pp65 antigenemia, time to clearance of pp65
      antigenemia after start of ganciclovir, CMV disease, invasive bacterial and
      fungal infections, time to neutrophil and platelet engraftment, acute graft
      versus-host disease, days of hospitalization, and overall survival rate among the
      3 groups. However, a subgroup analysis of CMV-seronegative recipients with a
      seropositive donor (D+/R-) showed a transiently improved survival rate by day 100
      in MSL-109 recipients (mortality: 60-mg group, 1/13; 15-mg group, 1/12; placebo
      group, 6/10 [P = .02 for 60-mg versus placebo groups; P = .08 for 15-mg versus
      placebo groups]); by the end of follow-up, the difference was no longer
      statistically significant. The improved survival rate in D+/R- patients could not
      be attributed to a reduction in CMV disease; however, MSL-109 was associated with
      improved platelet engraftment and less grade III to IV acute graft-versus-host
      disease in this subgroup. In a subgroup analysis of CMV-seropositive recipients
      of MSL-109 (D+/R+ and D-/R+), overall mortality was increased compared to that of
      the placebo group (P = .12 for the 60-mg versus placebo groups, P = .05 for the
      15-mg versus placebo groups, and P = .04 for the dose levels combined versus
      placebo). MSL-109 was well tolerated and no immune response to the drug was
      observed. Thus, MSL-109 was safe but did not reduce CMV infection in allogeneic
      HSCT recipients. The transient survival advantage seen early after
      transplantation in CMV D+/R- patients and the negative effect on survival in
      seropositive patients remain unexplained. Thus, there is no evidence that MSL-109
      is beneficial in CMV-seropositive HSCT recipients.

PMID- 11464978
TI  - Low incidence of transplantation-related acute complications in patients with
      chronic myeloid leukemia undergoing allogeneic stem cell transplantation with a
      low-dose (550 cGy) total body irradiation conditioning regimen.
AB  - Although allogeneic transplantation is a curative therapy for chronic myeloid
      leukemia (CML), treatment-related mortality is still a major cause of
      posttransplantation mortality, especially for patients older than 40 years. We
      investigated, in a phase II trial, the role of a low-dose (550 cGy) high-dose
      rate (35 cGy/min) single-exposure total body irradiation (TBI) conditioning
      regimen for allogeneic peripheral blood stem cell (PBSC) transplantation in
      patients with CML. Between June 1997 and August 2000, 30 adult patients with CML
      underwent cytokine-mobilized allogeneic PBSC transplantation from HLA-matched
      siblings following administration of cyclophosphamide (60 mg/kg per day
      intravenously on days -2 and -1) and single-dose TBI (550 cGy delivered at 30
      cGy/min on day 0). Cyclosporine A alone was administered for prophylaxis against
      graft-versus-host disease (GVHD). Median patient age was 47 years (range, 21-63
      years), with 23 patients (77%) older than 40 years. The preparative regimen was
      well tolerated. Grade 4 toxicities and oral mucositis were not observed. Graft
      failure did not occur. Severe acute GVHD was observed in 5 patients (17%). The
      median follow-up was 23 months (range, 6-39 months). Cytogenetic or hematologic
      relapse was detected in 3 patients (10%), 2 of whom subsequently entered
      remission following a taper of immunosuppression. Nonrelapse mortality occurred
      in 5 patients (17%), and the Kaplan-Meier estimate of survival at 2 years was 83%
      (95% confidence interval, 70%-97%). In summary, this low-dose TBI-based
      preparative regimen resulted in uniform donor engraftment, with markedly reduced
      organ toxicity and nonrelapse mortality, in this relatively older cohort of
      patients with CML.

PMID- 11464979
TI  - High-dose chemotherapy for rhabdomyosarcoma: where do we go from here.

PMID- 11464980
TI  - Overview of the treatment of infant central nervous system tumors:
      medulloblastoma as a model.

PMID- 11464981
TI  - Role of high-dose chemotherapy with hematopoietic stem cell rescue in the
      treatment of metastatic or recurrent rhabdomyosarcoma.
AB  - PURPOSE: This review summarizes the published data on the use of high-dose
      chemotherapy and hematopoietic stem cell rescue (HSCR) in the treatment of
      recurrent or metastatic rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Three
      hundred eighty-nine patients were identified from 22 articles selected by
      computer generated searching of MEDLINE (1979-present). One hundred seventy-seven
      patients had stage 4 disease and were treated during first complete remission
      (CRI). The remaining patients were treated during CR1/first partial remission
      (PR1) (110 patients), CR2/PR2 (53 patients), CR2 (12 patients), CR3 (1 patient),
      or treated with disease (36 patients). RESULTS: Patients treated during CR1 or
      CR1/PR1 had event-free survival (EFS) rates ranging from 24% to 29% at 3 to 6
      years from diagnosis and overall survival (OS) rates ranging from 20% to 40% at 2
      to 6 years after diagnosis according to data provided as Kaplan-Meier estimates.
      Studies without Kaplan-Meier estimates (n = 32) indicate that 12 patients (38%)
      with stage IV RMS treated during CR1 or CR1/PR1 were surviving 7 to 60 months
      from diagnosis, similar to patients with stage IV RMS treated on Intergroup
      Rhabdomyosarcoma Studies II or III. Patients treated during CR2, CR3, or with
      evidence of disease had a worse outcome with an estimated 3 years OS of 12% (n =
      51). Studies without Kaplan-Meier estimates (n = 27) indicate that four patients
      (15%) treated during CR2, CR3, or with disease were surviving 17 to 33 months
      after transplant. CONCLUSIONS: Based on these data, there does not appear to be a
      significant advantage to undergoing high-dose chemotherapy with HSCR for patients
      with relapsed or refractory high-risk RMS. Clearly, there is a need for
      incorporating new treatment strategies for patients with high-risk RMS.

PMID- 11464982
TI  - Paclitaxel for the treatment of progressive or recurrent childhood brain tumors:
      a pediatric oncology phase II study.
AB  - PURPOSE: To assess the efficacy and define the toxicity of paclitaxel given at a
      dosage of 350 mg/m2 every 3 weeks as a 24-hour continuous infusion to children
      with recurrent or progressive primary brain tumors. PATIENTS AND METHODS: Seventy
      three eligible patients, ages 4 months to 19 years, with progressive or recurrent
      primary brain tumors were treated according to a Pediatric Oncology Group (POG)
      phase II protocol with paclitaxel (POG 9330). Tumor histologic strata included:
      astrocytoma (n = 4), malignant glioma (n = 13), medulloblastoma (n = 16), brain
      stem glioma (n = 15), ependymoma (n = 13), and miscellaneous histologies (n =
      12). All patients had previous histologic confirmation of a primary intracranial
      or spinal cord tumor with magnetic resonance imaging or computed tomography
      documentation of unequivocally measurable progressive or recurrent disease. All
      patients had received previous therapy including surgery, radiation therapy,
      and/or chemotherapy, but no patient had been previously treated on more than one
      phase II trial. Paclitaxel was administered as a 24-hour intravenous infusion at
      a dosage of 350 mg/m2 every 3 weeks. Neurologic and neuroradiologic reevaluations
      were performed after every second course. Patients were allowed to continue
      therapy for a total of 18 cycles in the absence of progressive disease or
      unacceptable toxicity. RESULTS: Seventy-five patients were enrolled onto the POG
      9330 protocol; two ineligible patients were removed from the study before
      receiving any therapy. Of the 73 eligible patients, 72 were evaluable for
      toxicity and 70 were either fully or partially evaluable for disease response.
      There was one complete response and three partial responses (5.7%). Twenty
      patients had stable disease for more than 2 months. Toxicities included mild
      nausea, central nervous system toxicity, myelosuppression, and febrile
      neutropenia, including one septic death. One grade 2 and two grade 3 allergic
      reactions occurred. No cardiac toxicities or arthralgias were reported.
      CONCLUSION: Paclitaxel is well tolerated in children with recurrent or
      progressive brain tumors at this dosage and schedule and may result in short-term
      disease stabilization in this patient population. The lack of a significant
      number of patients with measurable disease regression, however, precludes it from
      being identified as an active agent when administered as a single agent by 24
      hour continuous infusion.

PMID- 11464983
TI  - Absence of human herpesvirus-6 genome by polymerase chain reaction in children
      with Hodgkin disease: a Children's Cancer Group Lymphoma Biology Study.
AB  - BACKGROUND: Human herpesvirus-6 (HHV6) has been implicated in adult lymphomas but
      the role that HHV6 has in lymphomagenesis is unclear. Because primary infection
      occurs in children, a prospective study was undertaken to detect HHV6 in those
      with pediatric Hodgkin disease (HD). OBSERVATIONS: Tumor was obtained from
      children with HD entered on a Children's Cancer Group Biology Study. Polymerase
      chain reaction (PCR) was performed using HHV6 primers. All 47 specimens (40
      nodular sclerosing; 3 lymphocyte predominant; 3 mixed cellularity; and 1
      unclassified) were negative for HHV6. CONCLUSIONS: The results demonstrate no
      HHV6 sequence in childhood HD.

PMID- 11464984
TI  - Lack of prognostic significance of intratumoral angiogenesis in nonmetastatic
      osteosarcoma.
AB  - BACKGROUND: A need exists to stratify patients with nonmetastatic osteosarcoma
      into risk subcategories to administer risk-adapted therapy. Intratumoral
      angiogenesis determined at diagnosis may have a prognostic significance in this
      malignancy. PATIENTS AND METHODS: The authors performed a retrospective
      immunohistochemical study on archival pathologic material from patients with
      nonmetastatic osteosarcoma, excluding patients with purely chondroblastic tumors
      associated with hypovascularity of the cartilaginous stroma. Representative
      sections from the diagnostic biopsies were stained with a murine monoclonal
      antibody directed against CD34, an endothelial cell marker. Two pathologists
      unaware of the patients' long-term outcome counted microvessels in 10 microscopic
      fields from the most active areas of neovascularization. RESULTS: Between March
      1988 and December 1996, 15 girls and 14 boys (median age 12.6 y, range 4.3-18.3)
      were identified. Seven patients had died of metastatic disease at a median of 3.4
      years (range 0.8-7.4) after diagnosis; 22 were alive with no evidence of disease
      at a median follow-up of 6.8 years (range 2.7-11.4). There was no significant
      difference in the number of microvessels per field (pathologist 1, median 19 vs.
      18.5; pathologist 2, median 15 vs. 10) between survivors or patients who died of
      metastatic disease. The correlation between the measurements of the two
      pathologists was excellent (correlation coefficient 0.87). CONCLUSIONS:
      Intratumoral neovascularization determined at diagnosis does not correlate with
      long-term outcome in patients with nonmetastatic osteosarcoma. A prospective
      study is necessary to confirm these results.

PMID- 11464985
TI  - Intravenous anesthesia with propofol for painful procedures in children with
      cancer.
AB  - OBJECTIVE: To study the safety and efficacy of propofol-based intravenous
      anesthesia in children with cancer undergoing painful procedures. METHODS: This
      study is a retrospective analysis of data collected from 52 consecutive children
      who underwent 335 procedures using propofol anesthesia. These data were routinely
      collected in all patients: time to induction, duration of the procedure, time to
      recover, and the doses of the drugs used. Monitoring with electrocardiography and
      pulse oximetry was continuous during the procedure; blood pressures were recorded
      before and after the procedure and every 5 to 10 minutes during the procedure.
      The patients received one of these four propofol-based intravenous regimens
      according to the anesthesiologist's preference: propofol only; propofol plus
      fentanyl; propofol plus midazolam; or propofol, fentanyl, and midazolam. The
      efficacy of sedation was rated by this scoring system: 3 = no movement during
      procedure; 2 = minimal movement that did not interfere with the procedure; 1 =
      moderate movement requiring physical restraint to complete the procedure.
      RESULTS: There were six episodes of mild hypoxia (oxygen saturation 85%-94%) and
      one episode of laryngospasm. None required intubation. Two patients had agitation
      and one patient had emesis during the postrecovery phase. There was no difference
      in the efficacy of sedation between the four regimens. Patients receiving the
      combination of propofol, fentanyl, and midazolam received the least amount of
      propofol and required the least time to recover. There were no life-threatening
      complications. CONCLUSIONS: Propofol-based anesthesia, when administered by an
      anesthesiologist in a controlled setting, is safe and effective for performing
      painful procedures in children with cancer.

PMID- 11464986
TI  - Vidarabine therapy for severe chronic active Epstein-Barr virus infection.
AB  - PURPOSE: Severe chronic active Epstein-Barr virus infection (SCAEBV) is an
      intractable disease with a poor prognosis, and a definitive treatment has not
      been established. We administered vidarabine to patients with natural killer (NK)
      cell-type SCAEBV and evaluated clinical and virologic effects. PATIENTS AND
      METHODS: Four patients with SCAEBV were enrolled in this study. These patients
      had various symptoms, including fever, chronic hepatitis, hepatosplenomegaly, and
      hypersensitivity to mosquito bites. All patients had increased numbers of NK
      cells in their peripheral blood, and most of these were infected with EBV. Viral
      load was measured by in situ hybridization and quantitative polymerase chain
      reaction (PCR). RESULTS: The patients all responded to the therapy, and their
      symptoms improved. After the therapy, the number of NK cells in their peripheral
      blood decreased. In two patients who were closely monitored, the viral load
      measured by in situ hybridization and quantitative PCR decreased in parallel with
      the symptomatic improvement. After discontinuing this drug, the patient's
      symptoms returned and the Epstein-Barr virus load increased again. CONCLUSION:
      These results indicate that vidarabine therapy is a therapeutic choice to control
      SCAEBV, although its effect may be transient.

PMID- 11464987
TI  - Feasibility study of IL-11 and granulocyte colony-stimulating factor after
      myelosuppressive chemotherapy to mobilize peripheral blood stem cells from
      heavily pretreated patients.
AB  - PURPOSE: Pediatric patients with solid tumors treated with prolonged dose
      intensive chemoradiotherapy are poor mobilizers of peripheral blood stem cells
      (PBSC). We have conducted a pilot study to mobilize PBSC in eight pediatric
      patients with relapsed solid tumors using ifosfamide, carboplatin, and etoposide
      (ICE) followed-up by IL-11 plus granulocyte colony-stimulating factor (G-CSF).
      PATIENTS AND METHODS: Patients received ifosfamide 1.8 g/m2 per day for 5 days,
      carboplatin 400 mg/m2 per day for 2 days, and etoposide 100 mg/m2 per day for 5
      days. After completion of ICE chemotherapy, patients received daily subcutaneous
      injections of G-CSF (5 microg/kg per day) and IL-11 (50-100 microg/kg per day)
      until peripheral stem cell apheresis. RESULTS: The median age was 11 years.
      Diagnosis included three relapsed Hodgkin disease, three relapsed central nervous
      system tumors, one relapsed Wilms tumor, and one relapsed rhabdomyosarcoma. The
      median number of apheresis procedures required to obtain 5 x 10(6) CD34+ cells/kg
      was one. The mean +/- standard error of mean (SEM) total CD34+ cells collected
      was 14.0+/-2.7 x 10(6)/kg. The mean +/- SEM total CD34+/CD41+ cells collected was
      4.6+/-1.9 x 10(6)/kg. Seven of the eight patients have subsequently undergone
      myeloablative chemotherapy with autologous PBSC transplantation and have
      reconstituted hematopoiesis with a median time to neutrophil recovery of 10 days
      and platelet recovery of 15.5 days. CONCLUSIONS: We conclude that the regimen of
      ICE/IL-11 plus G-CSF is successful in mobilizing large numbers of CD34+ PBSC
      cells with a limited number (one) of apheresis collections in patients that have
      previously been heavily pretreated with chemotherapy/radiotherapy.

PMID- 11464988
TI  - Hydroxyurea therapy for pediatric patients with hemoglobin SC disease.
AB  - PURPOSE: Hydroxyurea (HU) has laboratory and clinical efficacy in hemoglobin SS
      (HbSS) disease, but its benefits in hemoglobin SC (HbSC) disease are unknown. A
      recent adult HbSC disease pilot trial with HU therapy documented a modest
      laboratory benefit. Our goal was to evaluate the laboratory and clinical
      responses of selected pediatric patients with severe HbSC disease to HU therapy.
      PATIENTS AND METHODS: As part of a retrospective case series, patients were
      selected from the Duke Pediatric Sickle Cell Program based on the frequency and
      severity of their vasoocclusive events or an episode of acute chest syndrome.
      Oral HU therapy was started as a single daily dose and increased to the maximally
      tolerated dose based on myelosuppression. Laboratory evaluation was performed at
      baseline and monthly thereafter. Once the maximum tolerated dose was reached,
      laboratory data were monitored bimonthly. RESULTS: We treated six severely
      affected pediatric HbSC patients with HU for a median of 27 months. Mean
      corpuscular volume increased significantly (+26 fL) without change in hemoglobin
      concentration (-0.1 g/dL); neutrophils decreased significantly. Percentage of
      fetal hemoglobin (+8.5%) and percentage of F cells (+35.7%) increased
      significantly. Two experienced only mild and reversible toxicity. CONCLUSION: The
      laboratory responses in our pediatric patients with HbSC disease were striking,
      with increases in percentage of fetal hemoglobin and percentage of F-cells
      approaching responses observed in adult and pediatric patients with HbSS disease.
      All patients improved clinically. Our findings demonstrate that HU therapy
      benefits pediatric patients with severe HbSC disease, although larger clinical
      trials of HU therapy in HbSC disease are warranted.

PMID- 11464989
TI  - Parvovirus B19 infection in a child with acute lymphoblastic leukemia during
      induction therapy.
AB  - Immunocompromised children, including those undergoing chemotherapy treatment of
      malignant disease, are at particular risk for infection with parvovirus B19.
      However, these patients' attenuated immune responses may obscure the serologic
      and clinical manifestations of the infection. The authors describe a patient
      undergoing induction therapy for acute lymphoblastic leukemia whose parvovirus
      B19 infection was identified by the incidental detection of giant pronormoblasts
      and absence of normal mature erythroid precursors, characteristic of parvovirus
      infection, on a routine bone marrow examination. Intravenous immunoglobulin was
      administered and the patient's aplastic anemia resolved completely within 3
      weeks. This highlights the importance of alertness to the possibility of
      parvovirus infection in children with cancer.

PMID- 11464990
TI  - Thyroid carcinoma after successful treatment of osteosarcoma: a report of three
      patients.
AB  - We report three cases of papillary thyroid carcinoma occurring after successful
      treatment of osteosarcoma. Only one of the three patients received radiation
      therapy (to the chest) as part of the primary treatment of osteosarcoma. The
      onset of thyroid carcinoma occurred between 8 and 16 years from the cessation of
      osteosarcoma therapy. All patients are alive and disease-free from both
      malignancies. Whereas the association between osteosarcoma and thyroid carcinoma
      has not previously been recognized, there have been five case reports of these
      two entities occurring in the same patient. Three of these cases occurred in
      patients with Werner syndrome. None of the patients reported here had physical
      stigmata of Werner syndrome or a family history consistent with a hereditary
      cancer syndrome. Thyroid carcinoma occurs infrequently in patients with
      osteosarcoma, but in view of the rarity of these two disorders, this association
      may represent an inherited predisposition to these malignancies.

PMID- 11464991
TI  - Hepatic mesenchymal hamartoma in a neonate: a case report and review of the
      literature.
AB  - To describe an unusual presentation of mesenchymal hamartoma in a critically ill
      neonate necessitating a novel therapeutic embolization before definitive
      resection. An unusual presentation of a large hepatic mass in a newborn
      complicated by pulmonary hypertension and vascular "steal" with renal
      insufficiency is presented. The mass was initially successfully embolized, but
      then revascularized, necessitating resection in an attempt to improve the
      clinical status of the critically ill neonate. The resected mass was a
      mesenchymal hamartoma with a necrotic center and extensive arterial
      collateralization. The patient began improving immediately after resection.
      Mesenchymal hamartoma may present in the neonate as a diagnostic dilemma. This is
      the first case report describing persistent pulmonary hypertension and renal
      compromise from this tumor. Embolization as a therapeutic modality to address
      this tumor is described. The cause of the persistent and severe pulmonary
      hypertension remains unclear,but may be related to the tumor.

PMID- 11464992
TI  - Infantile cytomegalovirus-associated autoimmune hemolytic anemia.
AB  - Autoimmune hemolytic anemia (AIHA) is a hematologic disorder that is rarely seen
      in infants and young children. Most cases are associated with viral or bacterial
      infection, but the immunologic events leading to hemolysis are poorly understood.
      We describe two infants with severe cytomegalovirus (CMV)-associated warm
      antibody AIHA. One case was immunohematologically analyzed and showed suggestive
      evidence that endogenous anti-CMV IgG antibodies were the pathogenic antibodies
      leading to hemolysis, implicating a possible causal relationship between AIHA and
      CMV infection. Both patients were ultimately treated with intravenous CMV immune
      globulin, with subsequent improvement. These cases suggest that investigation for
      the presence of CMV in infantile AIHA is warranted and that CMV immune globulin
      should be considered as a therapeutic option.

PMID- 11464993
TI  - Lymphomatoid papulosis and Ki-1+ anaplastic large cell lymphoma occurring
      concurrently in a pediatric patient.
AB  - Lymphomatoid papulosis (LyP) is a benign, self-healing, papular eruption that can
      wax and wane over the course of time. Transformation to T-cell lymphoma has been
      well documented in 10% to 20% of adults with LyP, but there are have been no
      cases reported in patients younger than age 26 years. We describe the first
      pediatric patient, a 16-year-old girl, who had clinical features of LyP and
      concurrently was found to have a lesion diagnosed as Ki-1+ anaplastic large cell
      lymphoma. After treatment with chemotherapy, she has been in continuous remission
      for 16 months.

PMID- 11464994
TI  - Ehrlichiosis infection in a 5-year-old boy with neutropenia, anemia,
      thrombocytopenia, and hepatosplenomegaly.
AB  - Ehrlichiosis should be considered in the differential diagnosis of any patient
      with recent fever, pancytopenia, hepatosplenomegaly, and history of tick
      exposure. We present a previously healthy 5-year-old boy who was referred to the
      Hematology-Oncology Clinic to consider a bone marrow etiologic process after his
      pediatrician discovered progressive neutropenia, anemia, thrombocytopenia, and
      hepatosplenomegaly accompanied by 2 days of fever. Bone marrow aspirate and
      biopsy were nonrevealing. Because of the history of a recent tick bite, a
      diagnosis of ehrlichiosis infection was considered and ultimately confirmed by
      IgG-specific serum testing. The patient's fever was treated symptomatically with
      acetaminophen, and symptoms resolved on their own without intervention.
      Ehrlichiosis is a tick-borne infection that occurs throughout the spring and
      summer, often causing findings that mimic a malignancy or serious hematologic
      disorder. The diagnosis should be considered in any person living in tick
      infested areas and can be confirmed by polymerase chain reaction or serum
      antibody titers. Treatment with doxycycline can lead to rapid clinical
      improvement if the diagnosis is made early.

PMID- 11464995
TI  - Bilateral subdural effusions related to disease activity in familial
      hemophagocytic lymphohistiocytosis in an 8-month-old infant.
AB  - An 8-month-old girl had classic features of hemophagocytic lymphohistiocytosis
      (HLH). A presumptive diagnosis of familial hemophagocytic lymphohistiocytosis was
      made on the basis of her age and the presence of parental consanguinity. In view
      of abnormal neurologic findings at presentation, a magnetic resonance imaging
      scan was performed and showed bilateral proteinaceous subdural effusions. These
      resolved within 1 week of commencement of chemotherapy for the primary condition.
      These subdural effusions were the only objective documentations of central
      nervous system involvement, along with an increased cerebrospinal fluid protein
      level. We also report other radiologic findings of HLH, which are of use in
      strengthening this diagnosis in individuals in whom the diagnosis is strongly
      suspected.

PMID- 11464996
TI  - Abnormal number of X chromosomes and neuroblastic tumors.

PMID- 11464997
TI  - The embryology, classification, epidemiology, and genetics of facial clefting.
AB  - Facial clefting results from a variety of genetic and environmental causes. It
      occurs when developing facial processes fail to fuse, merge, or interact; the
      clefts range from mild to severe. The embryology and classification of these
      clefts have been characterized. Moreover, the epidemiology has been determined
      from population data. Unfortunately, complete understanding of the genetics of
      facial clefting has not been completely uncovered. Facial clefts exist within
      more than 300 syndromes with only a few being commented on in this article. As
      the human genome project continues, the understanding of facial clefting and its
      syndromes may continue to improve. Such knowledge could advance diagnosis and
      treatment of the patient and counseling of the affected family. Other articles
      within this issue address the management of these clefts.

PMID- 11464998
TI  - Maxillary deformities.
AB  - The management of congenital maxillary anomalies can be managed with ease by the
      well trained facial plastic surgeon. An understanding of dental anatomy,
      occlusion, and the rudiments of cephalometric analysis are important
      prerequisites for this type of work. A background in the management of facial
      trauma prepares the surgeon for the surgery involved. A sense of aesthetics is
      required to adequately anticipate what the final cosmetic and functional outcome
      should be in these cases. The Le Fort III osteotomy is particularly difficult,
      especially if there is associated hypertelorism that requires craniotomy.
      Significant experience in the less demanding operations of the maxilla coupled
      with experience in skull base surgery is essential before tackling this demanding
      procedure.

PMID- 11464999
TI  - Management of congenital nasal anomalies.
AB  - Congenital nasal anomalies are rare disorders that may present challenges to the
      facial plastic and reconstructive surgeon. These anomalies are extremely varied
      and result from a wide range of disordered embryonic development. A basic
      understanding of nasal and facial development is helpful in understanding these
      anomalies. In addition, proper respect for the unique challenges of nasal surgery
      on infants and children is crucial to best serve the patient. This allows a
      proper work-up and consideration of appropriate treatment options before surgical
      repair.

PMID- 11465000
TI  - Management of congenital anomalies of the neck.
AB  - This article, although not exhaustive, highlights the most common congenital
      anomalies of the neck. The diagnostic possibilities for a neck mass are
      extensive, and congenital malformations account for a minority of neck masses.
      The misdiagnosis and inappropriate treatment of a neck mass may have serious
      consequences for the patient. Therefore, a standardized and complete approach to
      the evaluation of neck masses is required. As stressed in this article, a
      thorough history and physical examination form the cornerstones of such an
      evaluation. The fact that congenital lesions of the neck have varied
      manifestations and may present at any age should always be considered.

PMID- 11465001
TI  - Otoplasty.
AB  - When multiple techniques are described to address a single condition, it is
      axiomatic that no single technique is ideal. Using mattress sutures to create an
      antihelical fold when one is absent provides benefits that outweigh the risks of
      this technique. It is a technique that can be learned quickly and mastered with
      experience. Goode's successful revision otoplasties with mattress sutures suggest
      that excessively springy ears are not the reason for failure. His results suggest
      that technical errors may be responsible for the lack of success at the initial
      procedure. No technique is without complications or limitations, and this
      technique is no exception. Conservative resection of the concha just medial to
      the lateral edge with reapproximation to the cauda helicis offers a quick,
      reliable approach to prominent conchal bowls. Prominence of the lobule was not
      described in detail. The lobule should, of course, be corrected if it contributes
      to the ear deformity. Chosen operative techniques should be adaptable to various
      deformities, and it is preferable, therefore, that the surgeon is comfortable
      with multiple techniques. The first step in this level of comfort is to acquire a
      detailed knowledge of ear anatomy. Only by having a firm grasp of the normal can
      the abnormal be understood precisely. Although a sound technical platform is
      required to achieve superior results, excellence is achieved only by a thorough,
      detailed preoperative analysis. A combination of mattress sutures to address the
      antihelix and lateral resection of the conchal bowl produces excellent results in
      most cases. Applying a rote technique to all deformities, however, is ineffective
      and will compromise results. Superior outcomes can be attained only with command
      of a combination of acute diagnostic skills, knowledge of various surgical
      techniques, and the ability to execute those techniques.

PMID- 11465002
TI  - Management of the cleft palate.
AB  - Oral clefts are among the most common of all birth defects. The exact etiology of
      palatal clefting is unclear, however, it is believed to be a multifactorial
      disruption of embryologic morphogenesis. Evaluation of these patients is complex
      and requires a thorough understanding of palatal anatomy and embryology. A team
      approach is used to addresses the varied anatomic, genetic, and psychosocial
      issues that surround these patients and their families. This article reviews the
      anatomy, embryology, epidemiology, diagnosis, and treatment of children with
      cleft palate.

PMID- 11465003
TI  - Auricular reconstruction in congenital anomalies of the ear.
AB  - In looking at the use of autogenous cartilage for auricular reconstruction as a
      corrective option for congenital anomalies of the ear, it is obvious that it has
      become refined to the point that the surgical outcome typically pleases patients
      and their families if their expectations are realistic. Thus, surgeons are able
      to help ward off the agonizing abuse that these young patients are inevitably
      subjected to when born with deformities that are visible to peers. Delay of
      reconstruction beyond age 10 can lead to significant, and possibly, permanent
      psychologic sequelae resulting from harassment. Key elements of successful
      auricular reconstruction are careful staging of surgeries, effective
      communication with family as to expectations and results, and selection of a
      surgeon with extensive experience. The risk versus reward question can be
      answered clearly by one look at the face of a delighted child who is moved to
      tears when his or her bandages are removed; parents, of course, are equally
      gratified. Although more studies are needed to pinpoint specific problems and
      forestall complications, this is certainly a viable surgical series that parents
      of children with microtia would do well to consider thoroughly. At the same time,
      this author strongly encourages plastic surgeons to fine-tune their skills in
      this area so that the operation can be made more widely available. Extreme
      satisfaction is inherent in perfecting and using this complex orchestration of
      staged procedures.

PMID- 11465004
TI  - Management of velopharyngeal competence.
AB  - Velopharyngeal dysfunction is common in patients with a repaired cleft palate or
      unrepaired submucous cleft palates. The optimal time of surgical repair is 4 to 6
      years of age after a thorough speech evaluation and speech therapy. Assessment of
      the velopharyngeal defect during speech allows the surgeon to customize the
      surgery to the patient. Patients require careful monitoring postoperatively for
      obstructive sleep apnea.

PMID- 11465005
TI  - Management of the cleft lip deformity.
AB  - Repair of the unilateral cleft lip deformity is a challenging and rewarding
      procedure. Historically, many techniques have been described to reconstruct the
      unilateral cleft lip. These have included straight-line repairs and various
      geometric flap closures. The rotation-advancement flap technique of Millard is a
      reliable and versatile method for repair of the unilateral cleft lip deformity.
      This technique allows lip repair and tip rhinoplasty while camouflaging the scars
      in the newly formed philtral border. If properly applied, the rotation
      advancement repair produces excellent functional and aesthetic results (Figs. 18A
      and 18B).

PMID- 11465006
TI  - Management of the cleft lip nasal deformity.
AB  - Management of the cleft lip nasal deformity offers a unique and ongoing challenge
      in facial plastic surgery. Although there has been no consensus regarding the
      optimal timing and technique for surgical repair of this deformity, the authors
      have found a three-tiered approach to be satisfactory. This approach involves a
      primary rhinoplasty performed at the time of the initial cleft lip repair to
      address reconstruction of the nasal floor and sill, columellar lengthening,
      repositioning of the alar base, and repositioning of the skin and mucosa of the
      lower lateral cartilage. Following alveolar bone grafting, an intermediate
      rhinoplasty is often performed at 6 to 10 years of age through an open approach
      to correct the cartilaginous lower nasal deformity. A delayed rhinoplasty is then
      performed in the later teenage years to correct the bony dorsal deformity and the
      various causes of nasal obstruction.

PMID- 11465007
TI  - Management of craniofacial neurofibromatosis.
AB  - The problem with neurofibromatosis is that it has always been classified from a
      pathological point of view. This really does not help when it comes to clinical
      management. This article presents a classification that relates to the severity
      of the condition and to its clinical management. In the head and neck area, the
      important region from the point of view of treatment, is the orbit and its
      contents. It is possible to classify the neurofibromatosis of the facial area in
      three grades, and these signify the severity of orbital involvement. This
      directly relates to the surgical management of these patients. Once this system
      is adopted, surgical decision-making is relatively easy, although the execution
      of the management is complex.

PMID- 11465008
TI  - Vascular anomalies of the head and neck.
AB  - Vascular abnormalities of the head and neck are relatively uncommon lesions. An
      understanding of these anomalies based on their pathogenesis and natural history
      clearly divides them into hemangiomas and vascular malformations. Treatment
      strategies that are reasonable and predictable can then be devised based on the
      aforementioned factors.

PMID- 11465009
TI  - Correction of nonsyndromal craniosynostosis.
AB  - Correction of craniosynostosis requires close collaboration between the
      craniofacial surgeon and the neurosurgeon. Typically, nonsyndromal
      craniosynostosis patients will require only one operation to correct the cranial
      vault deformity. The procedures usually are undertaken between 3 and 6 months of
      age. Any gaps are filled in with new bone because the dura is highly osteogenic.
      The early correction of these deformities can avoid future facial deformities as
      a result of restricted skull base growth causing maxillary and secondary
      mandibular deformities.

PMID- 11465010
TI  - The star systems: overview and use in determining antiepileptic drug choice.
AB  - An explosion in antiepileptic drug (AED) therapy began in the 1990s with the
      licensing of 9 new chemical entities and more to come. Important differences
      between AEDs may not be detected by regulatory trials, which are designed to
      satisfy licensing requirements and often diverge considerably from everyday
      clinical practice. The Star Systems have been developed as evidence-based yet
      pragmatic and flexible models for comparing AEDs. Each drug has been judged
      across a range of criteria, including mechanism of action, pharmacokinetics, ease
      of use, efficacy, tolerability, safety, interaction profile and a 'comfort
      factor'. A score has been allocated under each category and systems have been
      devised for patients with newly diagnosed epilepsy and those with difficult-to
      control seizures requiring combination therapy. The choice of treatment should
      involve assessment of patient-related factors, accurate classification of seizure
      type and syndrome, married with an understanding of the pharmacology of the AEDs.
      A staged management plan should be formulated when initiating treatment with the
      aim of preventing the development of refractory epilepsy. When using combinations
      of AEDs, the mechanism of action of each agent should be taken into
      consideration. Such an individualised approach to management will optimise the
      chance of attaining remission and help many more patients achieve a fulfilling
      life.

PMID- 11465011
TI  - Compulsive buying disorder: definition, assessment, epidemiology and clinical
      management.
AB  - Compulsive buying disorder is characterised by excessive or poorly controlled
      preoccupations, urges or behaviours regarding shopping and spending, which lead
      to adverse consequences. Compulsive buying disorder has been estimated to affect
      from 2 to 8% of the general adult population in the US; 80 to 95% of those
      affected are female. Onset occurs in the late teens or early twenties, and the
      disorder is generally chronic. Psychiatric comorbidity is frequent, particularly
      mood, anxiety, substance use, eating and personality disorders. Treatment has not
      been well delineated, but individual and group psychotherapy, cognitive
      behavioural therapy and 12-step programmes may be helpful. Debt consolidation and
      credit counselling will be appropriate for many individuals who have compulsive
      buying disorder. Serotonin (5-hydroxytryptamine; 5-HT) re- uptake inhibitors may
      help some patients regulate their buying impulses. Self-help books are also
      available.

PMID- 11465013
TI  - The economics of selective serotonin reuptake inhibitors in depression: a
      critical review.
AB  - The prevalence of depression and the high costs associated with its treatment
      have increased interest in pharmacoeconomic evaluations of drug treatment,
      particularly in the 1990s as the use of selective serotonin (5-hydroxytryptamine;
      5-HT) reuptake inhibitors (SSRIs) expanded substantially. This review presents
      results from specific studies representing the key study designs used to address
      the pharmacoeconomics of SSRI use: retrospective administrative database
      analyses, clinical decision analysis models, and randomised clinical trials.
      Methodological considerations in interpreting results are highlighted. In
      retrospective administrative database analyses, most comparisons have been made
      between SSRIs and tricyclic antidepressants (TCAs). A few studies have addressed
      differences between SSRIs. The studies focused on healthcare cost (to payer) and
      cost-related outcomes (e.g. treatment duration, drug switching). Although SSRIs
      are generally associated with higher drug acquisition costs than are TCAs, total
      healthcare costs are at least offset, if not decreased, by reductions in costs
      associated with use of SSRIs. Although studies from the early 1990s show some
      advantage for fluoxetine, the results are limited by use of data from shortly
      after the introduction of paroxetine and sertraline; studies from the mid- 1990s
      on that compare drugs within the SSRI class show general equivalence in terms of
      cost. Important methodological advances are occurring in retrospective studies,
      with selection bias and other design limitations being addressed statistically.
      Clinical decision analysis models permit flexibility in terms of ability to
      specify different alternative treatment scenarios and varying durations.
      Sensitivity analysis aids interpretability, although model inputs are limited by
      data availability. Results from short term (1 year duration or less) studies
      comparing SSRIs and TCAs suggest that SSRIs are more cost effective or that there
      is no difference. Longer term studies (lifetime Markov models) focus more on the
      impact of maintenance antidepressant therapy and show more mixed results,
      generally favouring SSRIs over TCAs. The results indicate that the effect of
      SSRIs is mainly through prevention of relapse. Important assumptions of these
      models include fewer serious adverse effects and lower treatment discontinuation
      rates with SSRIs. Naturalistic clinical trials provide greater generalisability
      than traditional randomised clinical trials. One naturalistic trial found that
      nearly half of TCA-treated patients switched to another antidepressant within 6
      months; only 20% of SSRI-treated patients switched. Cost differences between
      groups were minimal. These studies indicate few differences in medical costs,
      depression outcomes and health-related quality of life between TCAs and
      fluoxetine, although fewer fluoxetine-treated patients switched treatment.

PMID- 11465014
TI  - Nature and nurture in ALS.

PMID- 11465015
TI  - Quality of life in ALS.

PMID- 11465016
TI  - Mechanism and treatment of motoneuron degeneration in ALS: what have SOD1 mutants
      told us?
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that
      causes motoneuron degeneration, skeletal muscle atrophy, paralysis and death. The
      identification of mutations in Cu,Zn superoxide dismutase (SOD1) as a genetic
      cause of this disease has led to the creation of a number of in-vitro and in-vivo
      models. Experiments have been carried out in these model systems to address
      fundamental questions related to the disease: (1) what is the nature of toxicity
      of the mutated SOD1? (2) what are the cellular targets and pathways that lead to
      neuronal degeneration? (3) what makes motoneurons particularly vulnerable to the
      toxicity of the mutant enzyme? and (4) are there effective treatments for ALS
      based on current hypotheses regarding the disease mechanism? Current research on
      these questions is reviewed.

PMID- 11465017
TI  - Amyotrophic lateral sclerosis: toxins and environment.
AB  - The role of environmental influences in the aetiopathogenesis of amyotrophic
      lateral sclerosis (ALS) has exercised minds since the 19th century. Despite
      strong hunches that environmental agents might be implicated in the causation of
      ALS, research seeking more objective evidence has generally yielded results which
      have been confusing and difficult to understand in terms of a unitary
      aetiological hypothesis. This review attempts to draw this evidence together in
      the context of a semi-systematic review of the literature. Potential physical
      influences are described as well as the better known chemical factors. The
      interface with recent advances in molecular genetics is reviewed as well as foci
      of ALS variants as they occur in localized areas in various parts of the world.
      There is a discussion of large and small area geographical clustering and the
      review concludes by presenting a general view of the possible significance of
      these--at times--confusing pointers in the context of other current theories of
      the aetiology of ALS.

PMID- 11465018
TI  - Frameshift, nonsense and non amino acid altering mutations in SOD1 in familial
      ALS: report of a Japanese pedigree and literature review.
AB  - We demonstrated the clinical characteristics of each member of a family from Oki
      Island in western Japan, whose members have familial amyotrophic lateral
      sclerosis (FALS) with a 2-base pair (bp) deletion at codon 126 of Cu/Zn
      superoxide dismutase (SOD1) gene. Mean disease duration among the Oki family
      members was about 2 years. Long-term survivors with respiratory support presented
      disturbances in eye movement and urination toward the end stages of the disease.
      In addition, we focused on in-vitro instabilities in the frameshift and nonsense
      mutations, including the 2-bp deletion, as well as some deletional, insertional
      and intronic mutations. These mutations were all found within exon 4, exon 5 and
      intron 4. As for the durations of illness, there were no significant differences
      between FALS patients with these SOD1 mutations and those with point mutations,
      although the former cases were likely to have shorter disease durations. In cell
      culture experiments, SOD1 proteins with frameshift and nonsense mutations were
      extremely unstable and showed very short half-lives. We postulated that the in
      vitro instability of the mutant SOD1 might be related to the pathogenesis of
      FALS, e.g. through the mechanism of copper release.

PMID- 11465019
TI  - Expression of nitric oxide synthase isoforms in spinal cord in amyotrophic
      lateral sclerosis.
AB  - METHODS: Autoradiography with [3H]nitro-L-arginine (3HL-NNA) was used to quantify
      nitric oxide synthase (NOS), and immunocytochemistry to identify NOS isoforms, in
      spinal cord in amyotrophic lateral sclerosis (ALS) and controls. RESULTS: In
      controls NOS binding was marked only in the superficial dorsal horn, but in ALS
      tissue it was intense throughout the grey and white matter. A single population
      of binding sites was indicated in controls, but two populations in ALS. In the
      controls intense neuronal NOS (nNOS) immunoreactivity was present in numerous
      cells in the dorsal horn, and faint immunoreactivity in small and medium-sized
      cells in the ventral horn. Only weak immunoreactivity for inducible NOS (iNOS)
      and endothelial NOS (eNOS) was detectable in control tissue. In ALS, the pattern
      was broadly similar in the grey matter, but immunoreactivity for both nNOS and
      iNOS was present in white matter. CONCLUSION: Expression of abnormal variants of
      nNOS or increased expression of iNOS may have a role in motoneuron death in ALS.

PMID- 11465012
TI  - Glutamate receptors and nociception: implications for the drug treatment of pain.
AB  - Evidence from the last several decades indicates that the excitatory amino acid
      glutamate plays a significant role in nociceptive processing. Glutamate and
      glutamate receptors are located in areas of the brain, spinal cord and periphery
      that are involved in pain sensation and transmission. Glutamate acts at several
      types of receptors, including ionotropic (directly coupled to ion channels) and
      metabotropic (directly coupled to intracellular second messengers). Ionotropic
      receptors include those selectively activated by N-methyl-D-aspartate, alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate. Metabotropic
      glutamate receptors are classified into 3 groups based on sequence homology,
      signal transduction mechanisms and receptor pharmacology. Glutamate also
      interacts with the opioid system, and intrathecal or systemic coadministration of
      glutamate receptor antagonists with opioids may enhance analgesia while reducing
      the development of opioid tolerance and dependence. The actions of glutamate in
      the brain seem to be more complex. Activation of glutamate receptors in some
      brain areas seems to be pronociceptive (e.g. thalamus, trigeminal nucleus),
      although activation of glutamate receptors in other brain areas seems to be
      antinociceptive (e.g. periaqueductal grey, ventrolateral medulla). Application of
      glutamate, or agonists selective for one of the several types of glutamate
      receptor, to the spinal cord or periphery induces nociceptive behaviours.
      Inhibition of glutamate release, or of glutamate receptors, in the spinal cord or
      periphery attenuates both acute and chronic pain in animal models. Similar
      benefits have been seen in studies involving humans (both patients and
      volunteers); however, results have been inconsistent. More research is needed to
      clearly define the role of existing treatment options and explore the
      possibilities for future drug development.

PMID- 11465020
TI  - Agreement among three quality of life measures in patients with ALS.
AB  - AIM: To determine the concurrent validity of three self-administered health
      related quality of life (HRQOL) questionnaires when administered to patients with
      amyotrophic lateral sclerosis (ALS). BACKGROUND: ALS is the most common motor
      neuron disease among adults. As a rapidly progressive and fatal disease, ALS has
      devastating effects on the patient's relationships, functional capacity and
      mental health. HRQOL measures include information about patients' physical
      impairments, functional level, and psychosocial status. This study compares a
      tool designed for the ALS population, the Sickness Impact Profile ALS-19
      (SIP/ALS19), and two tools designed to be used in any population, the Quality of
      Well-being Scale SA (QWB SA), and the SF-36 Health Survey (SF-36). Correlation of
      the scores would suggest that each tool is valid as a stand-alone measurement of
      quality of life for this patient population. METHODS: The SIP/ALS-19, the SF-36,
      and the QWB SA were self-administered to 19 subjects diagnosed with ALS. The
      scores for each test were ranked and analyzed for agreement using the Spearman
      rank correlation coefficient. RESULTS: The SIP/ALS-19 demonstrated moderate to
      good correlation with the QWB SA and fair correlation with the SF-36. The SF-36
      had little to no correlation with the QWB SA. CONCLUSIONS: The study did not
      demonstrate significant correlation among the three quality of life measures. The
      SIP/ALS-19, SF-36, and QWB SA each have a different focus in measuring HRQOL. The
      healthcare practitioner should consider the patient's stage of disease, treatment
      goals, and type of interventions planned when selecting a HRQOL tool for the ALS
      patient.

PMID- 11465021
TI  - Brown-Vialetto-Van Laere syndrome: case report and literature review.
AB  - We describe a case of the Brown-Vialetto-Van Laere syndrome, which is a rare
      disorder characterized by progressive pontobulbar palsy associated with
      sensorineural deafness. More than 30 cases have been reported since the first
      case was described in 1894. We review the literature of this condition, comparing
      our case with those reported in the literature and emphasizing important features
      to improve our understanding of this syndrome.

PMID- 11465022
TI  - Treatable lower motor neuron disease due to vitamin D deficiency and secondary
      hyperparathyroidism.
AB  - Vitamin D deficiency and osteomalacia are frequently associated with muscle
      weakness and atrophy. We present a 78-year-old man with complaints of progressive
      painless weakness who was referred to us with a diagnosis of suspected motor
      neuron disease. Results of the neurological examination were remarkable, showing
      diffuse limb weakness and atrophy, rare fasciculations, normal sensory
      examination, no bulbar weakness, and no upper motor neuron signs.
      Electromyography revealed mild chronic changes, denervation and re-innervation,
      without fibrillations or positive waves. Serum laboratory studies showed an
      elevated serum parathyroid hormone and markedly reduced vitamin D level. Although
      the etiology of the vitamin D deficiency was not determined, the patient made a
      substantial clinical improvement following vitamin D therapy. Vitamin D
      deficiency and secondary hyperparathyroidism need to be included in the
      differential diagnosis of patients presenting with a progressive lower motor
      neuron disease.

PMID- 11465023
TI  - Phylogenetic--evolutionary approaches to bioinformatics.
AB  - Phylogenies of organisms are essential to investigating a range of evolutionary
      questions of interest to researchers in the field of bioinformatics. Phylogenies
      not only help to define how to study many evolutionary questions, they must also
      be taken into account when conducting statistical analyses. Here it is shown how
      phylogenies can be used to investigate variability along the sites of a gene,
      reconstruct ancestral states of ancient genes and proteins, identify and
      characterise events of parallel and convergent evolution, find events of gene
      duplication, analyse predictions from molecular clocks, seek evidence for
      correlated changes among different parts of the same gene or genome, and test
      theories of molecular evolution. A table of statistical and phylogenetic methods
      is presented.

PMID- 11465024
TI  - Getting started with Acedb.
AB  - Acedb is one of the more venerable pieces of Genomics software. Acedb was
      originally created in 1992 by Richard Durbin and Jean Thierry-Mieg to manage the
      data from the Caenorhabditis elegans mapping project and subsequently the C.
      elegans sequencing project. From beginnings as a C. elegans-specific tool, it has
      been continuously developed into a flexible suite of data management, display and
      scripting tools providing facilities for managing and annotation mapping
      information and DNA and peptide sequences. This paper gives a basic overview of
      the Acedb suite, and step-by-step guidance on how to download and install Acedb.
      It is intended to take an Acedb novice to stage where they can begin to
      experiment and explore the facilities that are available.

PMID- 11465025
TI  - Plant genome databases: from references to inference tools.
AB  - Plant genome databases play an important role in the archiving and dissemination
      of data arising from the international genome projects. Recent developments in
      bioinformatics, such as new software tools, programming languages and standards,
      have produced better access across the Internet to the data held within them. An
      increasing emphasis is placed on data analysis and indeed many resources now
      provide tools allied to the databases, to aid in the analysis and interpretation
      of the data. However, a considerable wealth of information lies untapped by
      considering the databases as single entities and will only be exploited by
      linking them with a wide range of data sources. Data from research programs such
      as comparative mapping and germplasm studies may be used as tools, to gain
      additional knowledge but without additional experimentation. To date, the current
      plant genome databases are not yet linked comprehensively with each other or with
      these additional resources, although they are clearly moving toward this. Here,
      the current wealth of public plant genome databases is reviewed, together with an
      overview of initiatives underway to bind them to form a single plant genome
      infrastructure.

PMID- 11465026
TI  - Farm animal genome databases.
AB  - The requirements for bioinformatics resources to support genome research in farm
      animals is reviewed. The resources developed to meet these needs are described.
      Resource databases and associated tools have been developed to handle
      experimental data. Several of these systems serve the needs of multinational
      collaborations. Genome databases have been established to provide contemporary
      summaries of the status of genome maps in a range of farm and domestic animals
      along with experimental details and citations. New resources and tools will be
      required to address the informatics needs of emerging technologies such as
      microarrays. However, continued investment is also required to maintain the
      currency and utility of the current systems, especially the genome databases.

PMID- 11465027
TI  - Human sequence variation and mutation databases.

PMID- 11465028
TI  - Sensitive protein comparisons with profiles and hidden Markov models.
AB  - Sequence database searches have become an important tool for the life sciences in
      general and for gene discovery-driven biotechnology in particular. Both the
      functional assignment of newly found proteins and the mining of genome databases
      for functional candidates are equally important tasks typically addressed by
      database searches. Sensitivity and reliability of the search methods are of
      crucial importance. The overall performance of sequence alignments and database
      searches can be enhanced considerably, when profiles or hidden Markov models
      (HMMs) derived from protein families are used as query objects instead of single
      sequences. This review discusses the concept of profiles, generalised profiles
      and profile-HMMs, the methods how they are constructed and the scope of possible
      applications in gene discovery and gene functional assignment.

PMID- 11465029
TI  - Epitope scanning using virtual matrix-based algorithms.
AB  - Protein sequence and expression databases (transcriptomes) contain the
      information required to identify epitopes capable of generating protective immune
      responses in humans. A key event in the initiation of an immune response against
      disease is the presentation of antigenic peptide epitopes to T cells by human
      leukocyte antigen (HLA) molecules. Computational filtering tools that allow the
      prediction of HLA/epitope interaction can be applied to sequence databases to
      select for candidate epitopes, thus minimising the subsequent amount of
      laboratory work. Here, the basic principles of epitope prediction and a summary
      of the available prediction approaches are presented, with a particular emphasis
      on the use of algorithms based on virtual HLA-II quantitative matrices, capable
      of predicting promiscuous HLA-II ligands.

PMID- 11465030
TI  - Data warehousing in molecular biology.
AB  - In the business and healthcare sectors data warehousing has provided effective
      solutions for information usage and knowledge discovery from databases. However,
      data warehousing applications in the biological research and development (R&D)
      sector are lagging far behind. The fuzziness and complexity of biological data
      represent a major challenge in data warehousing for molecular biology. By
      combining experiences in other domains with our findings from building a model
      database, we have defined the requirements for data warehousing in molecular
      biology.

PMID- 11465031
TI  - ARTEMIS: a tool for displaying and annotating DNA sequence.

PMID- 11465032
TI  - Human genome sequencing project.

PMID- 11465033
TI  - Comparing the success of different prediction software in sequence analysis: a
      review.
AB  - The abundance of computer software for different types of prediction in DNA and
      protein sequence analyses raises the problem of adequate ranking of prediction
      program quality. A single measure of success of predictor software, which
      adequately ranks the predictors, does not exist. A typical example of such an
      incomplete measure is the so-called correlation coefficient. This paper provides
      an overview and short analysis of several different measures of prediction
      quality. Frequently, some of these measures give results contradictory to each
      other even when they relate to the same prediction scores. This may lead to
      confusion. In order to overcome some of the problems, a few new measures are
      proposed including some variants of a 'generalised distance from the ideal
      predictor score'; these are based on topological properties, rather than on
      statistics. In order to provide a sort of a balanced ranking, the averaged score
      measure (ASM) is introduced. The ASM provides a possibility for the selection of
      the predictor that probably has the best overall performance. The method
      presented in the paper applies to the ranking problem of any prediction software
      whose results can be properly represented in a true positive-false positive
      framework, thus providing a natural set-up for linear biological sequence
      analysis.

PMID- 11465034
TI  - Information resources for the bioinformatician.
AB  - The collaborative computing project in biosequence and structure analysis (CCPII)
      was established to foster bioinformatics in the broad community and the UK
      research community in particular. A World-Wide Web site called 'The
      Bioinformatics Resource' has been created containing a comprehensive set of
      information resources of use to the bioinformatician. The activities of CCPII are
      complementary to other providers of molecular biology information such as the
      BIOSCI electronic communication forum, which was established to facilitate
      communication between professionals in the biological sciences.

PMID- 11465035
TI  - The untranslated regions of eukaryotic mRNAs: structure, function, evolution and
      bioinformatic tools for their analysis.
AB  - The crucial role of the non-coding portion of genomes is now widely acknowledged.
      In particular, mRNA untranslated regions are involved in many post
      transcriptional regulatory pathways that control mRNA localisation, stability and
      translation efficiency. A review is given of the most recent research works on
      the functional characterisation of eukaryotic mRNA untranslated regions. In order
      to make possible a systematic and detailed sequence analysis of mRNA untranslated
      regions (UTRs), a non-redundant database of metazoan mRNA untranslated sequences
      annotated for the occurrence of specific functional elements, UTRdb, was devised.
      These elements, whose consensus structure has been devised on the basis of
      experimental assays and of comparative analyses, have been collected in the
      UTRsite database. A suitable pattern-matching software has been devised to search
      UTRsite patterns in user-submitted sequences, also assessing their statistical
      significance. Structural, compositional and evolutionary features of untranslated
      sequences of metazoan mRNAs have been investigated showing peculiar intra- and
      interspecific patterns.

PMID- 11465036
TI  - Proteomic databases and software on the web.
AB  - In the wake of sequencing projects, protein function analysis is evolving fast,
      from the careful design of assays that address specific questions to 'large
      scale' proteomics technologies that yield proteome-wide maps of protein
      expression or interaction. As these new technologies depend heavily on
      information storage, representation and analysis, existing databases and software
      tools are being adapted, while new resources are emerging. This paper describes
      the proteomics databases and software available through the World-Wide Web,
      focusing on their present use and applicability. As the resource situation is
      highly transitory, trends and probable evolutions are discussed whenever
      applicable.

PMID- 11465037
TI  - Prediction and phylogenetic analysis of mammalian short interspersed elements
      (SINEs).
AB  - The presence of repetitive elements can create serious problems for sequence
      analysis, especially in the case of homology searches in nucleotide sequence
      databases. Repetitive elements should be treated carefully by using special
      programs and databases. In this paper, various aspects of SINE (short
      interspersed repetitive element) identification, analysis and evolution are
      discussed.

PMID- 11465038
TI  - Protein structure prediction methods for drug design.
AB  - Along the long path from genomic data to a new drug, the knowledge of three
      dimensional protein structure can be of significant help in several places. This
      paper points out such places, discusses the virtues of protein structure
      knowledge and reviews bioinformatics methods for gaining such knowledge on the
      protein structure.

PMID- 11465039
TI  - Tuberculosis vaccine design: influence of the completed genome sequence.
AB  - Tuberculosis continues to be a major health problem, with more adults dying from
      Mycobacterium tuberculosis than any other pathogen world-wide. With the onset of
      the HIV epidemic and an increase in drug-resistant M. tuberculosis strains, the
      need for an improved vaccine has become an international priority. The recent
      completion of the genome sequences for two M. tuberculosis strains provides a
      wealth of information that can be used to design new strategies for vaccine
      development. The challenge comes in making rational choices from among the 4,000
      genes of the most probable candidate immunogens or virulence genes.Thus, a well
      designed screen is needed to reduce the number of candidates that must be tested.
      Presently, the most valuable role that bioinformatics can play is to provide such
      a screen.

PMID- 11465040
TI  - Visualising gene expression in its metabolic context.
AB  - Relative changes in mRNA as well as protein levels induced by sublethal doses of
      antibiotics on bacteria are measured and results visualised in the context of
      metabolic pathway diagrams. The mRNA levels present at a given time point after
      the addition of the antibiotic are measured using microarrays from Affymetrix.
      Additionally, the relative amount of each protein synthesised during 3 minute
      intervals sampled at the given times is measured using radio-labelling followed
      by two-dimensional polyacrylamide gel electrophoresis and the subsequent analysis
      of the images produced by exposure to a phosphorimager. Metabolic pathway
      diagrams are both constructed in-house and imported from KEGG (Kyoto Encyclopedia
      of Genes and Genomes). Both protein and mRNA expression data can be displayed in
      the pathway diagrams such that the colour of the vectors or enzyme identifiers
      indicate the relative change in expression level and reproducibility.

PMID- 11465041
TI  - Exploring protein domain structure.
AB  - The protein databank contains coordinates of over 10,000 protein structures,
      which constitute more than 25,000 structural domains in total. The investigation
      of protein structural, functional and evolutionary relationships is fundamental
      to many important fields in bioinformatics research, and will be crucial in
      determining the function of the human and other genomes. This review describes
      the SCOP and CATH databases of protein structure classification, which define,
      classify and annotate each domain in the protein databank. The hierarchical
      structure, use and annotation of the databases are explained. Other tools for
      exploring protein structure relationships are also described.

PMID- 11465042
TI  - Sense and nonsense in the prediction of drug-drug interactions.
AB  - Drug interactions are always a major concern in medicine and within the
      pharmaceutical industry. Fatal drug interactions have been reported, and several
      prominent drugs have been withdrawn from the market because of serious adverse
      reactions related to drug interactions. Therefore, drug interactions represent
      not only a medical problem for clinicians, but also an economic loss for
      pharmaceutical companies. Today, many pharmaceutical companies are predicting
      potential interactions of new drug candidates in an attempt to minimize such
      losses and to more effectively safeguard the welfare of patients. Can in vivo
      drug interactions be predicted accurately from in vitro metabolic studies? Should
      the prediction be qualitative or quantitative? These are the fundamental
      questions that industrial drug metabolism scientists must confront daily.
      Prediction of in vivo drug interactions from in vitro metabolic data is highly
      controversial, because of the complexities of factors that are involved in drug
      interactions. Some scientists believe that quantitative prediction of drug
      interaction is possible, whereas others are less optimistic, and believe that
      quantitative prediction is extremely difficult, if not impossible. The purpose of
      this review is to present and discuss the technical problems inherent in
      estimating in vitro Ki values and in measuring inhibitor concentration at the
      active-site of enzymes. Theoretic considerations are briefly reviewed, and
      representative examples are drawn from literature to illustrate the sense and
      nonsense in predicting in vivo drug interactions.

PMID- 11465043
TI  - Experimental methods for studying drug uptake in the head and brain.
AB  - A number of techniques have been developed to study the disposition of drugs in
      the head and, in particular, the role of the blood-brain barrier (BBB) in drug
      uptake. The techniques can be divided into three groups: in-vitro, in-vivo and in
      situ. The most suitable method depends on the purpose(s) and requirements of the
      particular study being conducted. In-vitro techniques involve the isolation of
      cerebral endothelial cells so that direct investigations of these cells can be
      carried out. The most recent preparations are able to maintain structural and
      functional characteristics of the BBB by simultaneously culturing endothelial
      cells with astrocytic cells. The main advantages of the in-vitro methods are the
      elimination of anaesthetics and surgery. In-vivo methods consist of a diverse
      range of techniques and include the traditional Brain Uptake Index and indicator
      diffusion methods, as well as microdialysis and positron emission tomography. In
      vivo methods maintain the cells and vasculature of an organ in their normal
      physiological states and anatomical position within the animal. However, the
      shortcomings include renal and hepatic elimination of solutes as well as the
      inability to control blood flow. In-situ techniques, including the perfused head,
      are more technically demanding. However, these models have the ability to vary
      the composition and flow rate of the artificial perfusate. This review is
      intended as a guide for selecting the most appropriate method for studying drug
      uptake in the brain.

PMID- 11465044
TI  - The biotransformation of nitrogen containing xenobiotics to lactams.
AB  - The metabolism of nitrogen heterocyclics may lead to lactam formation. In early
      studies on xenobiotic metabolism lactams were identified as metabolites of
      nicotine, cyproheptadine, tremorine and prolintane. Now, because of the
      increasing availability of powerful analytical techniques, there are many
      instances of lactams being identified as metabolites. Lactam metabolites are
      formed from either iminium ions or carbinolamines. These two intermediates may
      have distinct mechanisms of formation but they can interconvert. There is
      evidence that the iminium ions are oxidized to lactams by aldehyde oxidases
      (cytosolic molybdenum hydroxylases). The tissue distribution and enzyme
      activities of aldehyde oxidase have been studied in several animal species.
      However, it is also known that iminium ions can undergo spontaneous hydrolysis to
      the corresponding carbinolamine. If the latter is stable it may undergo oxidation
      by cytochrome P-450 to form the lactam. Thus, species differences in lactam
      formation might be caused by differences in the concentrations of either
      cytochrome P450 isozymes or aldehyde oxidases. It appears that lactam formation
      is an end stage in the metabolism of N-heterocycles in that it is unlikely that
      the lactam will undergo hydrolysis to the corresponding amino acid. Such amino
      acids probably arise from the amino aldehydes that may be produced from ring
      opening of unstable carbinolamine intermediates. When microsomal preparations are
      incubated with the appropriate substrate in the presence of sodium cyanide the
      iminium ion may be trapped to produce a cyano compound. Such reactions have led
      to the proposal that iminium ions might react with nucleophilic sites of cellular
      macromolecules and so contribute to both the pharmacology and toxicology of N
      heterocyclic compounds. Other pathways for the formation of lactam metabolites
      involve the internal cyclization of precursor metabolites, e.g. the self
      condensation of an aldehyde group (formed during metabolism) with a neighboring
      amide group. However, spontaneous ring closures of amino acids to form lactams
      seem unlikely since it would be anticipated that the amino acid residue would
      exist as a stable zwitterion under physiological conditions. Thus, it is unlikely
      that lactams will undergo futile metabolism via hydrolytic ring opening followed
      by ring closure. Under extreme conditions such unanticipated ring closures may
      occur and the conditions of metabolite isolation may contribute to the occurrence
      of artifacts.

PMID- 11465045
TI  - Prostaglandin H synthases and their importance in chemical toxicity.
AB  - The metabolism of a xenobiotic is an important stage resulting in its
      toxification (bioactivation) or detoxification. The most common reaction is the
      oxidation catalyzed by the cytochrome P450 (CYP) enzyme system. An alternate
      enzyme for chemical oxidation is the prostaglandin H synthase (PGHS) also known
      as cyclooxygenase (COX). The PGHS is the initial enzyme in arachidonate
      metabolism and formation of prostanoids such as prostaglandins (PG),
      prostacyclins, and thromboxanes. However, 25 years ago it was found that during
      the reduction of the endogenous substrate, hydroperoxy-endoperoxide (PGG2) to
      hydroxy-endoperoxide (PGH2), the PGHS enzyme is capable to "co-oxidize"
      chemicals. In this reaction, a broad spectrum of chemicals can serve as electron
      donors such as phenolic compounds, aromatic amines, and polycyclic aromatic
      hydrocarbons. In contrast to numerous CYP enzymes in liver, the PGI is an
      alternate enzyme for xenobiotic metabolism in extrahepatic tissues. In respect of
      tissue distribution, PGHS can play an essential role in the bioactivation of e.g.
      procarcinogenic chemicals in certain target tissues that possess low CYP
      monooxygenase activity. Two PGHS isozymes have been identified: PGHS-1 and PGHS
      2, which have very similar kinetic properties, but differ in regard to expression
      and regulation. In recent studies it was shown that not only endogenous stimuli
      but also drugs and environmental chemicals can activate PGHS-2 expression.
      Therefore the PGHS enzymes provide two interesting aspects for pharmacology and
      toxicology: a) the co-oxidation of chemicals and b) the altered synthesis of
      prostanoids after exposure to certain xenobiotics which can be essential for
      their ultimate toxicity.

PMID- 11465046
TI  - Early ADME in support of drug discovery: the role of metabolic stability studies.
AB  - The area of Drug Discovery has undergone an amazing evolution in the past decade.
      This evolution is typified by the development of automated combinatorial
      synthesis and high throughput pharmacological testing. This, in turn, has lead to
      the ability to create and mine extensive databases and then model this new
      information. The overall result is a substantial increase in the rate of target
      identification, generation of new leads, and finally, optimization of those leads
      into clinical candidates. ADME studies have always played a critical role in
      helping to optimize the pharmacokinetic (PK) properties of new drugs thereby
      increasing their success rate. As a consequence of the increased throughput of
      drug discovery, ADME studies have evolved to keep pace. These so-called "early
      ADME" studies, are characterized by parallel processing and higher throughput
      than before. A primary concern of medicinal chemists is to design molecules that
      will have not only the desired activity, but also suitable potency and duration
      of action, which is influenced by pharmacokinetic properties such as
      bioavailability and half-life. This article focuses on a particular subset of
      eADME studies known as "metabolic stability", which can be an important
      contributor for a good pharmacokinetic profile. Metabolic stability studies
      represent the adaptation of more complex metabolism rate studies to a minimized
      system suitable for parallel processing of large numbers of compounds. The
      theoretical basis for metabolic stability lies in its relationship to the concept
      of metabolic intrinsic clearance. Typical metabolic stability protocols are
      discussed with respect to their relation to drug design. How metabolic stability
      studies have evolved to keep pace with advances in drug discovery is also
      discussed. Several case studies of the role of metabolic stability in drug design
      over the past few years are summarized to exemplify the utility of this kind of
      study. Finally, future trends in drug metabolism and analytical chemistry and how
      they may influence metabolic stability studies are reviewed.

PMID- 11465047
TI  - Toxicokinetics in drug development: an overview of toxicokinetic application in
      the development of PNU-101017, an anxiolytic drug candidate.
AB  - The importance of toxicokinetics in the drug development has been identified in
      the last decade. The main objectives of toxicokinetics in general are to define
      the drug bioavailability, dose proportionality, gender differences, and species
      differences in pharmacokinetics and metabolism, from which the target organ
      toxicity can be predicted and the safety doses in the first human clinical trial
      can be established. Toxicokinetic studies may also serve as a tool for the
      toxicologic pathologist in understanding models used for predicting and assessing
      drug-related toxic response. Toxicokinetics/toxicodynamics are critical to
      investigating the toxicological mechanism and understanding the comparative
      toxicity between animals and humans. This report presents an overview of the
      application of toxicokinetics and its impact in the drug development of PNU
      101017, a drug candidate for the treatment of anxioety. Serial specifically
      designed toxicokinetic studies identified a steep dose-response relationship
      between the clinical signs and PNU-101017 serum or CSF concentrations,
      characterized the centrally mediated respiratory depression as the toxicity
      leading to the lethality, and demonstrated marked species differences in the
      sensitivity to the toxic effects. These findings lead to a termination of PNU
      101017 development due to the safety concern in humans.

PMID- 11465048
TI  - Recent advances in biotransformation of CNS and cardiovascular agents.
AB  - Compound biotransformation is a very important research area for drug discovery
      and development. In this review, publications from the metabolism studies of ten
      compounds, seven CNS and three cardiovascular agents, from the Johnson & Johnson
      Corp. were reviewed. The seven CNS compounds are: three antipsychotic agents,
      mazapertine (arypiperazine analog), RWJ-46344 (arypiperidine analog) and
      risperidone (aryisoxazole-piperidine analog), one antidepressant, etoperidone
      (arypiperazine analog), one anxiolytic agent, fenobam (aryimidazole urea analog),
      one muscle relaxant, xilobam (pyrrolidinylidene urea analog), and one
      antiepileptic agent, topiramate (fructopyranose sulfamate analog). The three
      cardiovascular agents are: two arylalkylamine calcium channel blockers, bepridil
      and RWJ-26240, and one thioindolaminidine antianginal agent, RWJ-34130. Other
      antipsychotic and antidepressant agents with similar analogs (ziprasidone,
      trazodone and nefazodone) as well as other similar analogs of calcium channel
      blockers (verapamil) are discussed. In this article, excretion and metabolism (in
      vitro, in vivo) of compounds are reviewed from the CNS agents to the
      cardiovascular agents, including structures of parent compounds, their
      metabolites, metabolic pathways, and methods for the isolation, profiling,
      quantification and structural identification of unchanged compounds and
      metabolites. Pharmacological activities of parent compounds and their metabolites
      are also briefly discussed.

PMID- 11465049
TI  - Fluorine nuclear magnetic resonance, a privileged tool for metabolic studies of
      fluoropyrimidine drugs.
AB  - Fluorine-19 nuclear magnetic resonance (19F NMR) spectroscopy provides a highly
      specific tool for identifying fluorine-containing drugs and their metabolites in
      biological media. This article focuses on the application of 19F NMR to the
      metabolic studies of fluoropyrimidine drugs in clinical use. The value and
      difficulties encountered in investigations on drug metabolism are first
      discussed. The metabolism and disposition studies of the anticancer drug 5
      fluorouracil, the mainstay of antimetabolite treatment for solid tumors, and its
      prodrugs, doxifluridine and capecitabine, are then extensively reviewed. The
      studies dealing with the antimycotic agent, 5-fluorocytosine, as well as the
      novel anticancer drug, gemcitabine, are also considered. From in vitro (biofluids
      or tissue extracts) 19F NMR analysis, seven new metabolites of 5-fluorouracil,
      doxifluridine, capecitabine and 5-fluorocytosine were identified. Except two,
      they were only detected using this technique. This emphasizes the high analytical
      potential of in vitro 19F NMR. In vivo 19F NMR is non-invasive and thus allows
      the quantitative monitoring of the metabolism of 5-fluorouracil in the target
      tissue, e.g. the tumor, as well as its biodistribution. Another promising
      application is its ability to estimate the level of yeast cytosine deaminase gene
      expression in human tumors from the quantitative monitoring of 5-fluorouracil
      formation from the non-cytotoxic drug 5-fluorocytosine. Notwithstanding these
      successes, the limited sensitivity and spectral resolution of 19F NMR precludes
      its extensive applicability to all the fluorinated drugs.

PMID- 11465050
TI  - Paradigm shifts in the approaches for gene annotation.

PMID- 11465051
TI  - Discriminant analysis and its application in DNA sequence motif recognition.
AB  - Identification of functional motifs in a DNA sequence is fundamentally a
      statistical pattern recognition problem. Discriminant analysis is widely used for
      solving such problems. This paper will review two basic parametric methods: LDA
      (linear discriminant analysis) and QDA (quadratic discriminant analysis). Their
      usage in recognition of splice sites and exons in the human genome will be
      demonstrated.

PMID- 11465052
TI  - Prediction of exact boundaries of exons.
AB  - It is known that while the programs used to predict genes are good at determining
      coding nucleotides, there are considerable inaccuracies in the determination of
      the gene structural elements. Among them, the most notable is that of the exact
      boundaries of exons. In order to assess this, we had earlier reviewed various
      programs that predict potential splice sites and exons. The results led to the
      following two observations: (i) a high proportion of false positive splice sites
      from computational predictions occur in the vicinity of real splice sites; and
      (ii) current algorithms are misled to predict wrong splice sites more often when
      the coding potential ends within +/-25 nucleotides from real sites than when it
      ends at farther positions. In this report, we review decision tree models for
      human splice sites and the resultant software tool, namely SpliceProximalCheck,
      that discriminates such'proximal' false positives from real splice sites. Further
      presented is an integrated system (MZEF-SPC) with Splice ProximalCheck (SPC) as a
      front-end tool operating on the results of Michael Zhang's exon finder program.
      Examination of the output of the integrated program on an illustrative gene set
      revealed that as much as 61 of 93 MZEF-predicted false positive exons could be
      eliminated by SPC for a loss of only 3 out of 33 MZEF-predicted true positive
      exons.

PMID- 11465053
TI  - Comparative analysis of regulatory patterns in bacterial genomes.
AB  - Recognition of transcription regulatory sites in bacterial genomes is a
      notoriously difficult problem. There are no algorithms capable of making reliable
      predictions even for well-studied sites such as the CRP (cyclic AMP receptor
      protein) box. However, availability of complete bacterial genomes makes it
      possible to make reliable predictions with bad rules. This comparative approach
      is based on the assumption that sets of co-regulated genes are conserved in
      related bacteria. Thus true sites occur upstream of orthologous genes, whereas
      false candidates are scattered at random. This means not only that knowledge
      about regulation in well-studied genomes can be transferred to newly sequenced
      ones, but also that new members of regulons can be found. This paper reviews
      several recent studies. In particular, a detailed analysis of catabolite
      repression in gamma-purple bacteria is presented.

PMID- 11465054
TI  - Identification and functional modelling of DNA sequence elements of
      transcription.
AB  - Identification of transcriptional elements in large sequences is a very difficult
      task, as individual transcription elements (eg transcription factor binding
      sites,TF-sites) are not clearly correlated with regions exerting transcription
      control. However, elucidation of the molecular organisation of genomic regions
      responsible for the control of gene expression is an essential part of the
      efforts to annotate the genomic sequences, especially within the Human Genome
      Project. The task for bioinformatics in this context is twofold. The first step
      required is the approximate localisation of regulatory sequences in large
      anonymous DNA sequences. Once those regions are located, the second task is the
      identification of individual transcriptional control elements and correlation of
      a subset of such elements with transcriptional functions. Part of this second
      task can be achieved by constructing organisational models of regulatory regions
      like promoters which can reveal elements important for a gene class or the
      coexpression of a set of genes. Comparative genomics in non-coding regions (eg
      phylogenetic footprinting) is a very promising approach that allows
      identification of potential new regulatory elements which may be used in
      modelling approaches.

PMID- 11465055
TI  - Genome sequence comparisons: hurdles in the fast lane to functional genomics.
AB  - An important computational technique for extracting the wealth of information
      hidden in human genomic sequence data is to compare the sequence with that from
      the corresponding region of the mouse genome, looking for segments that are
      conserved over evolutionary time. Moreover, the approach generalises to
      comparison of sequences from any two related species. The underlying rationale
      (which is abundantly confirmed by observation) is that a random mutation in a
      functional region is usually deleterious to the organism, and hence unlikely to
      become fixed in the population, whereas mutations in a non-functional region are
      free to accumulate over time. The potential value of this approach is so
      attractive that the public and private projects to sequence the human genome are
      now turning to sequencing the mouse, and you will soon be able to compare the
      human and mouse sequences of your favourite genomic region. We are currently
      witnessing an explosion of computer tools for comparative analysis of two genomic
      sequences. Here the capabilities of two new network servers for comparing genomic
      sequences from any pair of closely related species are sketched. The Syntenic
      Gene Prediction Program SGP-I utilises sequence comparisons to enhance the
      ability to locate protein coding segments in genomic data. PipMaker attempts to
      determine all conserved genomic regions, regardless of their function.

PMID- 11465056
TI  - Arabidopsis genome analysis as exemplified by analysis of chromosome 4.
AB  - During the last decade the small cruciferous plant Arabidopsis thaliana has
      become a model organism for flowering plants. Sequencing and analysis of the
      Arabidopsis genome is nearing completion. Beside an overview on methods and
      strategies for Arabidopsis genome analysis, a summary of the results from the
      first analysis is presented. This includes an overview on chromosomal
      organisation and topological features as well as a first comparison with other
      genomes.

PMID- 11465057
TI  - Ontology-based knowledge representation for bioinformatics.
AB  - Much of biology works by applying prior knowledge ('what is known') to an unknown
      entity, rather than the application of a set of axioms that will elicit
      knowledge. In addition, the complex biological data stored in bioinformatics
      databases often require the addition of knowledge to specify and constrain the
      values held in that database. One way of capturing knowledge within
      bioinformatics applications and databases is the use of ontologies. An ontology
      is the concrete form of a conceptualisation of a community's knowledge of a
      domain. This paper aims to introduce the reader to the use of ontologies within
      bioinformatics. A description of the type of knowledge held in an ontology will
      be given.The paper will be illustrated throughout with examples taken from
      bioinformatics and molecular biology, and a survey of current biological
      ontologies will be presented. From this it will be seen that the use to which the
      ontology is put largely determines the content of the ontology. Finally, the
      paper will describe the process of building an ontology, introducing the reader
      to the techniques and methods currently in use and the open research questions in
      ontology development.

PMID- 11465058
TI  - HOBACGEN: homologous bacterial genes database.

PMID- 11465059
TI  - Issues in predicting protein function from sequence.
AB  - Identifying homologues, defined as genes that arose from a common evolutionary
      ancestor, is often a relatively straightforward task, thanks to recent advances
      made in estimating the statistical significance of sequence similarities found
      from database searches. The extent by which homologues possess similarities in
      function, however, is less amenable to statistical analysis. Consequently,
      predicting function by homology is a qualitative, rather than quantitative,
      process and requires particular care to be taken. This review focuses on the
      various approaches that have been developed to predict function from the scale of
      the atom to that of the organism. Similarities in homologues' functions differ
      considerably at each of these different scales and also vary for different domain
      families. It is argued that due attention should be paid to all available clues
      to function, including orthologue identification, conservation of particular
      residue types, and the co-occurrence of domains in proteins. Pitfalls in database
      searching methods arising from amino acid compositional bias and database size
      effects are also discussed.

PMID- 11465060
TI  - Links between kinetic data and sequences in the alpha/beta-hydrolases fold
      database.
AB  - While the number of sequenced genes is increasing dramatically, the number of
      different protein structural families is expected to be more limited. Changes in
      enzymatic activity or protein interactions can dramatically modify the role of
      homologous proteins in different organisms or mutants. However, experimental data
      associated with sequences or mutations stored in databases are often limited to a
      short description of the enzymatic pathway, molecular interaction or phenotype
      associated with the changes in amino acid sequence. In the alpha/beta-hydrolases
      fold database ESTHER, we are experimenting with links between experimental
      kinetic data and sequences, mutations and protein structures. This effort will
      lead to the integration of pharmacological data with genome-wide databases.

PMID- 11465061
TI  - Protein function from the perspective of molecular interactions and genetic
      networks.
AB  - Protein function is a complex notion, which is now receiving renewed attention
      from a bioinformatics and genomics perspective. After a general discussion of the
      principles of experimental methods employed to decipher gene/protein function,
      the contributions made by new, high-throughput methods in terms of function
      discovery are discussed. Recent work on functional ontologies and the necessity
      to describe function within the context of hierarchical levels of complexity are
      presented. The concepts of molecular interactions and genetic networks are then
      discussed, leading to a useful new framework with which to describe protein
      function using new tools such as 2D interaction maps. Finally, it is proposed
      that interaction data could be used to develop new methods for the functional
      classification of proteins. An example of functional comparisons on a real data
      set of yeast chromosomal proteins is presented.

PMID- 11465062
TI  - Defining the function of a gene.

PMID- 11465063
TI  - Making sense of score statistics for sequence alignments.
AB  - The search for similarity between two biological sequences lies at the core of
      many applications in bioinformatics. This paper aims to highlight a few of the
      principles that should be kept in mind when evaluating the statistical
      significance of alignments between sequences. The extreme value distribution is
      first introduced, which in most cases describes the distribution of alignment
      scores between a query and a database. The effects of the similarity matrix and
      gap penalty values on the score distribution are then examined, and it is shown
      that the alignment statistics can undergo an abrupt phase transition. A few types
      of random sequence databases used in the estimation of statistical significance
      are presented, and the statistics employed by the BLAST, FASTA and PRSS programs
      are compared. Finally the different strategies used to assess the statistical
      significance of the matches produced by profiles and hidden Markov models are
      presented.

PMID- 11465064
TI  - Phenotypic data in FlyBase.
AB  - Phenotypic analysis combined with molecular genetics is a powerful tool for
      mapping gene function onto the genome. Phenotypic data are, by their nature,
      descriptive, and as varied as the range of mutant phenotypes that can be
      presented by the organism under study. This paper discusses the mechanisms
      FlyBase has implemented to systematise published phenotypic data about
      Drosophila, and provides an introduction to the query tools available for the
      mining of the data. Though FlyBase is specific to Drosophila, the issues faced in
      devising protocols for capturing, storing and reporting data are the same issues
      faced by any database with an interest in using phenotypic data to maximise the
      potential of genomic analysis.

PMID- 11465065
TI  - From molecular activities and processes to biological function.
AB  - This paper describes how biological function can be represented in terms of
      molecular activities and processes. It presents several key features of a data
      model that is based on a conceptual description of the network of interactions
      between molecular entities within the cell and between cells. This model is
      implemented in the aMAZE database that presently deals with information on
      metabolic pathways, gene regulation, sub- or supracellular locations, and
      transport. It is shown that this model constitutes a useful generalisation of
      data representations currently implemented in metabolic pathway databases, and
      that it can furthermore include multiple schemes for categorising and classifying
      molecular entities, activities, processes and localisations. In particular, we
      highlight the flexibility offered by our system in representing multiple
      molecular activities and their control, in viewing biological function at
      different levels of resolution and in updating this view as our knowledge
      evolves.

PMID- 11465066
TI  - Functional information in SWISS-PROT: the basis for large-scale characterisation
      of protein sequences.
AB  - With the rapid growth of sequence databases, there is an increasing need for
      reliable functional characterisation and annotation of newly predicted proteins.
      To cope with such large data volumes, faster and more effective means of protein
      sequence characterisation and annotation are required. One promising approach is
      automatic large-scale functional characterisation and annotation, which is
      generated with limited human interaction. However, such an approach is heavily
      dependent on reliable data sources. The SWISS-PROT protein sequence database
      plays an essential role here owing to its high level of functional information.

PMID- 11465067
TI  - Ornithine aminotransferase, a potential target for the treatment of
      hyperammonemias.
AB  - Ornithine-delta-aminotransferase (OAT) (EC 2.6.1.13) is a pyridoxal-5' phosphate
      dependent mitochondrial matrix enzyme. It controls the L-ornithine (Orn) level in
      tissues by catalysing the transfer of the delta-amino group of Orn to 2
      oxoglutarate. The products of this reaction are L-glutamate-gamma-semialdehyde
      and L-glutamate. Among the compounds known to inhibit (or inactivate) OAT, only L
      canaline and (SS)-5-(fluoromethyl)ornithine [(SS)-5FMOrn] are selective for OAT.
      Treatment of laboratory animals with 5FMOrn causes a dramatic accumulation of Orn
      in most tissues and organs, and the enhanced formation of urea due to saturation
      of ornithine:carbamoyltransferase with its substrate. The enhancement of urea
      formation by increased endogenous levels of Orn is comparable with that produced
      by large doses of Orn and arginine, a treatment known to enhance the
      detoxification of ammonia. However, protection to lethal doses of ammonium salts
      by exogenous Orn is rapidly fading. In contrast, inactivation of OAT by a small
      dose of 5FMOrn renders a long-lasting protective effect against various forms of
      hyperammonemic states. Among these the reduction of ammonia concentrations in
      blood and tissues, and the reduction of the pathologic excretion of orotic acid
      to normal levels in mice with hereditary defects of the urea cycle, were most
      impressive. In human hereditary OAT deficiency the elevated intraocular
      concentrations of Orn are considered to be a cause of gyrate atrophy. This is
      presumably the reason, why OAT has not been considered as a therapeutically
      useful target. Chronic inactivation of OAT by repeated administration of 5FMOrn,
      caused elevated intraocular Orn concentrations, but this treatment had no effect
      on the function and histology of the visual system, or the behaviour of adult
      mice. The confirmation of this and related observations in higher species will
      show, whether OAT inactivation has potentials in the treatment of hyperammonemic
      states.

PMID- 11465068
TI  - Cysteine proteinases of trypanosome parasites: novel targets for chemotherapy.
AB  - The protozoan parasites, Trypanosoma brucei and T. cruzi, that cause sleeping
      sickness in sub-Saharan Africa and Chagas' Disease in Latin America,
      respectively, exert significant morbidity and mortality in man. Combinations of
      toxicity and differential efficacy of current drugs provide an urgent need to
      develop novel, cheap and effective chemotherapies. Research over the last decade
      with cultured trypanosomes and mice experimentally infected with these parasites
      has demonstrated that trypanosome cysteine proteinases are valid targets for the
      rational design of new drugs. In particular, potent peptidyl and peptidomimetic
      inhibitors of brucipain (a.k.a. trypanopain-Tb) and cruzain (a.k.a. cruzipain),
      the respective cysteine proteinases of T. brucei and T. cruzi, have proved
      trypanocidal. Efforts are ongoing to develop more specific non-toxic inhibitors
      of various chemistries with improved biological half-lives and biovailability
      characteristics. Here, the biochemical and biological properties together with
      the history, current status and perceived directions on the development of
      specific inhibitors of trypanosome cysteine proteinases will be reviewed.

PMID- 11465069
TI  - Protein kinase C as a drug target: implications for drug or diet prevention and
      treatment of cancer.
AB  - Protein kinase C (PKC) isoforms are serine/threonine kinases involved in signal
      transduction pathways that govern a wide range of physiological processes
      including differentiation, proliferation, gene expression, brain function,
      membrane transport and the organization of cytoskeletal and extracellular matrix
      proteins. PKC isoforms are often overexpressed in disease states such as cancer.
      In this review, PKC in a variety of cancers is discussed along with some specific
      cell biological mechanisms by which PKC exerts its function(s). The PKC family
      consists of several isoforms comprising three groups: classical, novel and
      atypical. Although PKC has been investigated for around 2 decades, only recently
      has the specific function of each isoform started to be elucidated and the
      isoforms evaluated for use as targets of drug action. Phorbol esters such as the
      tumor-promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or diacylglycerol (DAG)
      activate classical and novel PKC isoforms. Naturally occurring retinoids,
      antisense oligonucleotides against specific PKC isoforms and specific PKC
      inhibitors can block this activation. Beta carotene and retinoid derivatives act
      as anticarcinogenic agents and can antagonize some of the biological actions of
      phorbol esters and oxidants. Another important area of investigation is the use
      of antisense oligonucleotides to inhibit specific PKC isoforms. These compounds
      have proven effective in reducing specific types of cancer in rodents and humans
      and are currently used in clinical trials. This review examines PKC isoforms as a
      target of drug action with special emphasis on their use in cancer therapy.

PMID- 11465070
TI  - Modulation of the ceramide level, a novel therapeutic concept?
AB  - The sphingomyelin (SM) pathway is an ubiquitous and evolutionarily conserved
      signaling system in which ceramide (CA), generated from SM by the action of
      various isoforms of sphingomyelinases (SMases) functions as an important second
      messenger. Recent evidence suggests that branching pathways of sphingolipid
      metabolism mediate either apoptotic or mitogenic responses depending on cell type
      and the nature of the stimulus. Events involving SM metabolites and CA in
      particular include proliferation, differentiation and growth arrest as well as
      the induction of apoptosis. An improved understanding of SMase-dependent
      signaling may afford relevant insights into the pathogenesis of diseases and
      provide novel strategies and selective targets for a therapeutic intervention
      e.g. in cancer, cardiovascular and neurodegenerative diseases, HIV and septic
      shock. This article briefly summarizes the role of SMases in signaling pathways,
      its potential contribution in the development and maintenance of various
      pathobiological states and analyzes the perspective of a potentially isotype
      specifc inhibition of SMases as a novel therapeutic concept.

PMID- 11465071
TI  - Tandem pore domain K channels: an important site of volatile anesthetic action?
AB  - Despite over 150 years of clinical use, the mechanism and molecular elements by
      which volatile anesthetics produce unconsciousness are not established. Although
      enhanced activity of inhibitory neurotransmitter systems (GABAA) and depression
      of excitatory neurotransmitter systems (NMDA) probably contribute to the
      anesthetic state, the role of other ion channels families have also been studied.
      Potassium channels represent the largest group of mammalian ion channels and
      their activity to reduce neuronal excitability makes them viable candidates as
      sites of anesthetic action. Several studies from the 1970's and 80's identified
      volatile anesthetic enhancement of neuronal potassium currents. More recently, a
      new family of K channels with a unique structure (tandem pore domains) that may
      be responsible for baseline or background K currents have been isolated and some
      members of this family can be activated by volatile anesthetics. These emerging
      findings suggest a new molecular mechanism by which volatile anesthetics may
      mediate central nervous system depression.

PMID- 11465072
TI  - Conantokins: inhibitors of ion flow through the N-methyl-D-aspartate receptor
      channels.
AB  - Calcium flow through the ion channel of the N-methyl-D-aspartate receptor (NMDAR)
      has been implicated as contributing to a variety of neuropathologies. This
      receptor is a complex heteromeric oligomer consisting of different types of
      subunits, the nature of which governs its properties, as well as its response to
      a variety of agonists, antagonists, and other types of inhibitors. A new natural
      series of NMDAR inhibitors, the conantokins, have been shown to be present in the
      venoms of snails within the genus, Conus. These agents appear to function by
      inhibition of the spermine/spermidine stimulation of ion flow through the NMDAR
      channel. These small peptides (17-27 amino acid residues) are highly processed
      post-translationally. One such processing event is the vitamin K-dependent gamma
      carboxylation of glutamate, resulting in placement of gamma-carboxyglutamic acid
      residues in these peptides. As a result, these peptides then possess the ability
      to interact with divalent metal ions and concomitantly undergo a conformational
      alteration. Rational drug design based on the characteristics of these promising
      peptides requires knowledge of their properties and the manner in which they
      target the NMDAR. This review summarizes current knowledge in this area.

PMID- 11465073
TI  - Antitumor potential and possible targets of phenothiazine-related compounds.
AB  - Phenothiazines and its related compounds have shown diverse biological activities
      including psychotropic, anticancer and other pharmacological activities. Recent
      studies have suggested the possible interactions between phenothiazines and their
      physiological targets or potential receptors. New types of phenothiazine, such as
      "half-mustard type" phenothiazines and benzo[a]phenothiazines, have been
      synthesized. These compounds stimulated T-cell blast formation, natural killer
      cell activity (possibly via activation of monocytes and macrophages) and antibody
      dependent cellular cytotoxicity of human peripheral blood mononuclear cells, and
      showed cytotoxicity against several human cancer cell lines.
      Benzo[a]phenothiazines induced monocytic differentiation and apoptotic cell death
      (characterized by internucleosomal DNA fragmentation) in human myelogenous
      leukemic cell lines, but not in other cancer cell lines. These compounds also
      induced antimicrobial activity in vivo, possibly by host-mediated
      immunopotentiation. On the other hand, phenothiazines did not induce such
      immunopotentiation activity, but showed direct antibacterial activity in vitro.
      There was positive relation between their radical intensity and biological
      activities. These compounds did not show any apparent mutagenic activity, but
      rather be antimutagenic. These data suggest their possible applicability of "half
      mustard type" phenothiazines and benzo[a]phenothiazines for cancer chemotherapy.

PMID- 11465074
TI  - Normal and pathological erectile function: the potential clinical role of
      endothelin-1 antagonists.
AB  - Erectile dysfunction (ED) is a common problem, particularly in older men. The
      production of penile erection involves an interplay between autonomic nerves and
      locally released vasoactive mediators. Endothelin-1 (ET-1) is a peptide released
      from endothelium in the corpus cavernosum, which causes smooth muscle
      contraction. Recent studies have investigated the physiological significance of
      ET-1 in the control of erectile function and it may play a role in detumescence.
      There is also much evidence to link ET-1 to risk factors for ED. ET-1 antagonists
      may prove beneficial in the treatment of ED and also in prevention of long term
      deterioration of erectile function. These antagonists may also find a role when
      used in combination with agents, which are established for the treatment of ED.

PMID- 11465075
TI  - Membrane transporters and antifungal drug resistance.
AB  - Over the last 30 years or so, the incidence of invasive fungal infections in man
      has risen dramatically. Patients that become severely immunocompromised because
      of underlying diseases such as leukemia or recently, acquired immunodeficiency
      syndrome or patients who undergo cancer chemotherapy or organ transplantation,
      are particularly susceptible to opportunistic fungal infections. Although Candida
      species continue to be the major pathogenic fungi in these patients,
      cryptococcosis, aspergillosis, and coccidioidomycosis, among others, have become
      increasingly important mycoses. Antifungal drugs currently being used in clinic
      include polyene antibiotics, azole derivatives and 5-fluorocytosine. With the
      exception of the latter, all other drugs possess mechanisms of action aimed at
      disrupting the integrity of the fungal cell membrane by either interfering with
      the biosynthesis of membrane sterols or by inhibiting sterol functions. However,
      one significant obstacle preventing successful antifungal therapy is the dramatic
      increase in drug resistance, especially against azole antimycotics. Among the
      major mechanisms by which fungi invoke drug resistance is the overexpession of
      extrusion pumps able to facilitate the efflux of cytotoxic drugs from the cell
      thus leading to decreased drug accumulation and diminished concentrations. Since
      the initial observations that azole resistance by fungi may be caused by
      overexpression of multidrug efflux transporter genes, significant advances have
      been achieved primarily with Saccharomyces cerevisiae and Candida albicans. The
      purpose of this review is to discuss various aspects of multidrug resistance in
      fungi such as antifungal drug mechanisms of action and fungal molecular genetics
      in the context of targeted drug discovery. The role that membrane transporter
      proteins play in drug resistance in various species of Candida, Aspergillus and
      Cryptococcus will be address in more detail, as will be their importance as
      selective drug targets in the design of novel antifungal agents.

PMID- 11465076
TI  - New developments in anti-platelet therapies: potential use of CD39/vascular ATP
      diphosphohydrolase in thrombotic disorders.
AB  - Abnormal platelet reactivity has been linked to unstable angina, myocardial
      infarction, post angioplasty stenosis, cerebral ischemia, thrombotic stroke and a
      variety of inflammatory vascular disorders associated with transplantation. Drugs
      that inhibit blood coagulation, promote fibrinolysis or block platelet activation
      are important therapeutic agents in cardiovascular medicine. However, many of the
      current antiplatelet modalities are nonspecific, ineffective or associated with
      severe side effects that limit their usefulness. In this article, we discuss some
      basic aspects of platelet pathophysiology to illustrate the importance of ADP
      stimulation and signaling in platelet activation. CD39, the ATP
      diphosphohydrolase (ATPDase) expressed on quiescent vascular endothelium,
      modulates platelet purinoreceptor activity by the sequential hydrolysis of
      extracellular ATP or ADP directly to AMP. This thromboregulatory potential of
      CD39 has been recently demonstrated by the generation of mutant mice with
      disruption of the gene, and by a series of experiments where high level ATPDase
      expression has been attained by adenoviral vectors in the injured vasculature.
      Systemic administration of soluble derivatives of CD39 or targeted expression of
      the native protein to sites of vascular injury may have future therapeutic
      application.

PMID- 11465077
TI  - Recent advances in particulate-induced pulmonary fibrosis; for the application of
      possible strategy experimentally and clinically.
AB  - Chronic interstitial lung diseases including pneumoconiosis have pathological
      characteristics which alter the lung structure and function consequent to the
      accumulation and activation of inflammatory cells in the lower respiratory tract.
      These activated cells usually secrete the inflammatory and fibrogenic mediators.
      Of the diffuse parenchymal lung diseases, the majority have no known etiology and
      idiopathic pulmonary fibrosis (IPF) is the diagnosis most frequently encountered
      by clinicians. Pathogenic similarities between pneumoconiosis and IPF provide a
      strong basis for hypothesizing that environmental agents may cause IPF. Many case
      control studies have been published that provide further evidence for a number of
      associations between occupational and environmental exposures and IPF. Such
      reports support a strong evidence that IPF may be a heterogenous disorder
      associated with a number of environmental exposures. As a model of lung fibrosis,
      experimental pneumoconiosis is giving us a great information because crystalline
      silica is probably one of the most typical agent producing pulmonary fibrosis and
      the severity of its health effects and the widespread nature of exposure have
      been long recognized. Many papers provide evidence that particles have the
      potential to cause stimulation of phagocytes to release oxidants and such
      oxidative stress is believed to be a major factor in pulmonary inflammation
      followed by fibrotic change. Many kinds of cellular mediators are recognized as a
      implicating factor in this process including cell-to-cell interaction, enzymes,
      cytokines, arachidonic acid derivatives et al. Treatment of pneumoconiosis is an
      attractive and interesting topic. But, the mechanism of pathogenesis of
      pneumoconiosis is not thoroughly understood yet. Also, whether the process of
      fibrosis formation be retarded or not is questionable with some therapeutic
      trial. Therefore, a sensitive biomarker which is possible to estimate the
      pathological pathway in pneumoconiosis is needed. Our laboratory has studied
      particulate-induced pulmonary reaction for two decades consistently. This review
      will focus on signal transduction pathway involved in oxidative stress and some
      inhibitory agents with pleiotropic mechanism in pulmonary fibrosis. I will also
      introduce some data of animal studies with multidrug regimen as well.

PMID- 11465078
TI  - Drug-metabolizing enzymes: mechanisms and functions.
AB  - Drug-metabolizing enzymes are called mixed-function oxidase or monooxygenase and
      containing many enzymes including cytochrome P450, cytochrome b5, and NADPH
      cytochrome P450 reductase and other components. The hepatic cytochrome P450s
      (Cyp) are a multigene family of enzymes that play a critical role in the
      metabolism of many drugs and xenobiotics with each cytochrome isozyme responding
      differently to exogenous chemicals in terms of its induction and inhibition. For
      example, Cyp 1A1 is particularly active towards polycyclic aromatic hydrocarbons
      (PAHs), activating them into reactive intermediates those covalently bind to DNA,
      a key event in the initiation of carcinogenesis. Likewise, Cyp 1A2 activates a
      variety of bladder carcinogens, such as aromatic amines and amides. Also, some
      forms of cytochrome P450 isozymes such as Cyp 3A and 2E1 activate the naturally
      occurring carcinogens (e.g. aflatoxin B1) and N-nitrosamines respectively into
      highly mutagenic and carcinogenic agents. The carcinogenic potency of PAHs, and
      other carcinogens and the extent of binding of their ultimate metabolites to DNA
      and proteins are correlated with the induction of cytochrome P450 isozymes. Phase
      II drug-metabolizing enzymes such as glutathione S-transferase, aryl sulfatase
      and UDP-glucuronyl transferase inactivate chemical carcinogens into less toxic or
      inactive metabolites. Many drugs change the rate of activation or detoxification
      of carcinogens by changing the activities of phases I and II drug-metabolizing
      enzymes. The balance of detoxification and activation reactions depends on the
      chemical structure of the agents, and is subjected to many variables that are a
      function of this structure, or genetic background, sex, endocrine status, age,
      diet, and the presence of other chemicals. It is important to realize that the
      enzymes involved in carcinogen metabolism are also involved in the metabolism of
      a variety of substrates, and thus the introduction of specific xenobiotics may
      change the operating level and the existence of other chemicals. The mechanisms
      of modification of drug-metabolizing enzyme activities and their role in the
      activation and detoxification of xenobiotics and carcinogens have been discussed
      in the text.

PMID- 11465079
TI  - Is it possible to more accurately predict which drug candidates will cause
      idiosyncratic drug reactions?
AB  - The unexpected occurrence of idiosyncratic drug reactions during late clinical
      trials or after a drug has been released can lead to a severe restriction in its
      use or failure to release/withdrawal. This leads to considerable uncertainty in
      drug development and has led to attempts to try to predict a drug's potential to
      cause such reactions. It appears that most idiosyncratic drug reactions are due
      to reactive metabolites; however, many drugs that form reactive metabolites are
      associated with a very low incidence of idiosyncratic drug reactions. Therefore.
      screening drug for their ability to generate reactive metabolites is likely to
      cause the rejection of many good drug candidates. There is evidence to suggest
      that an idiosyncratic drug reaction is more likely if there is some "danger
      signal'. Thus drugs that cause some degree of cell stress or damage may be more
      likely to lead to a high incidence of idiosyncratic drug reactions. The exact
      nature of the putative danger signals is unknown. However, a screen of the
      effects of drugs known to be associated with a high incidence of idiosyncatic
      reactions using expression genomics and proteomics may reveal a pattern or
      patterns of mRNA and protein expression that predict which drugs will cause a
      high incidence of idiosyncratic drug reactions. Although idiosyncratic drug
      reactions are not usually detected in animal tests because they are just as
      idiosyncratic in animals as they are in humans, it is likely that drug reactive
      metabolites would also cause similar cell stress in animals. It is more likely
      that in most cases it is differences in the immune response to the reactive
      metabolites that determine which individuals will develop an idiosyncratic
      reaction. If the expression of certain proteins in animals treated with a drug
      candidate could be used as a screening method to predict a drug's potential to
      cause a high incidence of idiosyncratic drug reactions, it would greatly
      facilitate the development of safer drugs.

PMID- 11465080
TI  - UDP-glucuronosyltransferases.
AB  - Glucuronidation represents a major pathway which enhances the elimination of many
      lipophilic xenobiotics and endobiotics to more water-soluble compounds. The UDP
      glucuronosyltransferase (UGT) family catalyzes the glucuronidation of the
      glycosyl group of a nucleotide sugar to an acceptor compound (aglycone) at a
      nucleophilic functional group of oxygen (eg, hydroxyl or carboxylic acid groups),
      nitrogen (eg, amines), sulfur (eg, thiols), and carbon, with the formation of a
      beta-D-glucuronide product. At this time, over 35 different UGT gene products
      have been described from several different species. UGTs have been divided into
      two distinct subfamilies based on sequence identities, UGT1 and UGT2. The UGT1
      gene subfamily consists of a number of UGTs that result from alternate splicing
      of multiple first exons and share common exons 2-5. The substrate specificities
      of the various isoforms have been examined in cultured cell experiments, and
      include bilirubin, amines, and planar and bulky phenol. The UGT2 gene family is
      different in that the UGT2 mRNAs are transcribed from individual genes. The UGT2
      subfamily consists of numerous enzymes which catalyze the glucuronidation of a
      diverse chemical base including steroids, bile acids, and opioids. Until
      recently, the liver has been the major focus for studying the metabolism of
      xenobiotics and endobiotics. Several groups have identified extrahepatic tissues
      that express UGT isoforms including the kidney, gastrointestinal tract and brain.
      This review discusses the two UGT gene families, substrate specificities, and the
      recent discoveries of UGTs in extrahepatic tissues.

PMID- 11465081
TI  - Hepatic disposition of electrophilic acyl glucuronide conjugates.
AB  - Acyl glucuronides are a unique class of electrophilic metabolites, capable of non
      enzymatic reactions including acylation and/or glycation of endogenous
      macromolecules, hydrolysis to reform the parent aglycone, and intra-molecular
      rearrangement. Three human UDP-glucuronosyltransferases (UGTs) catalyzing the
      hepatic glucuronidation of carboxylic acid drugs have been identified, UGT1A3,
      UGT1A9 and a UGT2B7 variant. Within the liver, acyl glucuronides also undergo
      enzymatic hydrolysis by beta-glucuronidase and esterases which, like the UGTs,
      are located in the endoplasmic reticulum. In addition, the liver also transports
      acyl glucuronides between the sinusoidal circulation and bile. Due to their
      polarity, membrane transport of acyl glucuronides is carrier-mediated, resulting
      in the establishment of significant concentration gradients between sinusoidal
      circulation, hepatocyte and bile, in the order of 1:50:5,000 in these
      compartments, respectively. As a result of exposure to high acyl glucuronide
      concentrations, the liver is a major target of protein adduct formation.
      Dipeptidylpeptidase IV, UGTs and tubulin have been identified as intra-hepatic
      targets of adduct formation by acyl glucuronides. Adduct formation results in
      altered protein activity and potentially contributes to hepatotoxicity. Hepatic
      protein adducts are also immunogenic and may cause immune mediated cytotoxicity.
      Both intra- and extra-hepatic exposure to acyl glucuronides depends not only on
      the efficiency of glucuronidation and hydrolysis by the liver, but also on the
      efficiency of the hepatic membrane transport systems. Thus, changes in membrane
      transporter activities, as may occur due to saturation or drug-drug interactions,
      can significantly affect acyl glucuronide disposition, adduct formation and the
      disposition of parent aglycone, thereby affecting clinical efficacy and toxicity
      of acyl glucuronide forming drugs.

PMID- 11465082
TI  - Human flavin-containing monooxygenase: substrate specificity and role in drug
      metabolism.
AB  - The human flavin-containing monooxygenase (FMO3) is a prominent enzyme system
      that converts nucleophilic heteroatom-containing chemicals, drugs and xenobiotics
      to more polar materials that are more efficiently excreted in the urine. The
      substrate specificity for FMO 3 is distinct from that of FMO1. Human FMO3 N
      oxygenates primary, secondary and tertiary amines whereas human FMO1 is only
      highly efficient at N-oxygenating tertiary amines. Both human FMO1 and FMO3 S
      oxygenate a number of nucleophilic sulfur-containing substrates and in some
      cases, does so with great stereoselectivity. Human FMO3 is sensitive to steric
      features of the substrate and aliphatic amines with linkages between the nitrogen
      atom and a large aromatic group such as a phenothiazine of at least five carbons
      are N-oxygenated significantly more efficiently than those substrates with two or
      three carbons. For amines with smaller aromatic substituents such as
      phenethylamines, often these compounds are efficiently N-oxygenated by human
      FMO3. Currently, the most promising non-invasive probe of in vivo human FMO3
      functional activity is the formation of trimethylamine N-oxide from
      trimethylamine that comes from dietary choline. (S)-Nicotine N-1'-oxide formation
      can also be used as a highly stereoselective probe of human FMO3 function for
      adult humans that smoke cigarettes. Finally, cimetidine S-oxygenation or
      ranitidine N-oxidation can also be used as a functional probe of human FMO3. With
      the recent observation of human FMO3 genetic polymorphism and poor metabolism
      phenotype in certain human populations, variant human FMO3 may contribute to
      adverse drug reactions or exaggerated clinical response to certain medications.
      Knowledge of the substrate specificity for human FMO3 may aid in the future
      design of more efficacious and less toxic drugs.

PMID- 11465083
TI  - Interferon-gamma-induced tryptophan degradation: neuropsychiatric and
      immunological consequences.
AB  - Tryptophan is a constituent of proteins and in parallel it represents a source
      for mainly two pivotal biochemical pathways: the generation of 5
      hydroxytryptamine (serotonin), and the formation of kynurenine by the enzymes
      tryptophan pyrrolase (TP) and indoleamine 2,3-dioxygenase (IDO). IDO is induced
      by interferon-gamma (IFN-gamma) in a broad variety of cells. Therefore, enhanced
      tryptophan degradation is observed in diseases and disorders concomitant with
      cellular immune activation, e.g. infectious diseases, autoimmune diseases,
      malignant diseases as well as in pregnancy. IFN-gamma-derived tryptophan
      degradation may represent an effector mechanism within in the comprehensive
      network of immune stimulation. In addition, the cytostatic and, respectively,
      antiproliferative properties on e.g., T-lymphocytes may contribute to the
      immunomodulatory function of IFN-gamma. However, especially in states of
      persistent immune activation increased tryptophan catabolism leads to the
      depletion of free serum tryptophan and to the accumulation of neuroactive
      kynurenine metabolites. As a consequence, serotonergic functions may be affected,
      and the neurotoxic properties of kynurenine derivatives may lead to neuronal
      disorders evoking neurological/psychiatric symptoms. This notion provides a basis
      for the better understanding of mood disorders and related syptoms in chronic
      diseases. Moreover, IDO could represent a link between the immunological network
      and neuroendocrine functions with far reaching consequences regarding to the
      psychological status of patients.

PMID- 11465084
TI  - Accelerator mass spectrometry in pharmaceutical research and development--a new
      ultrasensitive analytical method for isotope measurement.
AB  - Accelerator mass spectrometry (AMS) permits the measurement of elemental isotopes
      at the individual atom level. The main application of AMS in drug discovery and
      development will be in the analysis of 14-carbon (14C). The principle behind AMS
      is the separation of individual positively charged atoms through mass, charge and
      momentum differences. In order to obtain the high-energy charge state required
      for separation, negative atoms are accelerated through a high voltage field (up
      to 10 million volts) generated by a tandem Van de Graaff accelerator. In the
      middle of the accelerator, the outer valency electrons are stripped from the atom
      and the resulting charged species are separated and counted. For 14C, AMS counts
      the number of individual atoms rather than measuring radioactive decays. The
      result is that AMS is up to one million times more sensitive than decay counting.
      Radioactivity levels as low 0.0001 dpm can be detected using AMS. The exquisite
      sensitivity of AMS analysis means that much lower amounts of 14C can be used than
      for conventional counting methods. This makes it easier to use 14C for in vitro,
      preclinical and clinical research programmes. As 14C poses both a biological and
      environmental hazard, AMS permits much lower doses to be used. Human drug mass
      balance studies have been conducted with doses of 50 nanoCuries and below.
      Radioactive HPLC metabolite profiles of plasma extracts from subjects given
      nanoCurie doses of 14C-labelled drug have been obtained by injecting as little as
      0.25 dpm onto an HPLC column. In studies of biologics, biosynthetically 14C
      labelled recombinant protein has been produced with a specific radioactivity
      sufficient to conduct human clinical studies with AMS analysis. For one human
      recombinant protein an increase in sensitivity of 2,000-fold over ELISA was
      obtained with AMS measurement. AMS is an enabling technology that should prove of
      value in increasing human and environmental safety as well as allowing new
      research directions to be followed.

PMID- 11465085
TI  - Neutrophil-specific alloantigen NB1, finally cloned but many questions remain.

PMID- 11465086
TI  - Molecular basis of the neutrophil glycoprotein NB1 (CD177) involved in the
      pathogenesis of immune neutropenias and transfusion reactions.
AB  - The human granulocyte alloantigen NB1, recently clustered as CD177, is
      heterogenously expressed on neutrophils of 88-97% of healthy individuals. Since
      its molecular nature has remained unknown, we isolated NB1 glycoprotein from
      granulocyte lysate by immunoaffinity chromatography. MALDI-TOF mass spectrometry
      identified a 50,556 Da glycoprotein which was reduced to 43,069 Da after removal
      of N-linked carbohydrates. Following N-terminal amino acid sequencing and NB1
      specific primer construction, rapid amplification of cDNA ends PCR yielded a
      1,614-bp cDNA for NB1. COS-7 cells transfected with the cDNA expressed
      immunoreactive NB1 glycoprotein. A 1,311-bp sequence was identified to be the
      entire coding region. The 5' and 3' untranslated regions consist of 27 bp and 276
      bp, respectively. The open reading frame codes for 437 amino acids of which the
      first 21 form the signal peptide. The remaining 416 residues form a N-terminal
      extracellular protein with two cysteine-rich domains, three N-linked
      glycosylation sites and short transmembrane and cytoplasmic segments including a
      glycosyl-phosphatidylinositol attachment (omega) site. Database searches revealed
      homology to Ly-6 (uPAR) domain, suggesting that NB1 belongs to urokinase
      plasminogen activator receptor/CD59/Ly-6 snake toxin superfamily.

PMID- 11465087
TI  - A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non
      hematopoietic tissues.
AB  - By contrast to well-defined Fc gamma and Fc epsilon receptors, the structural and
      functional characteristics of Fc mu receptor are unclear. We have recently
      described a novel mouse Fc receptor, designated Fc alpha/mu receptor, and its
      human homologue, which bind both IgM and IgA. Here we show that the Fc alpha/mu
      receptor is expressed on mature, but not immature, B lymphocytes and acquires the
      ability to bind IgM and IgA antibodies after stimulation of B lymphocytes.
      Moreover, stimulation with phorbol 12-myristate 13-acetate increased endocytosis
      of IgM-coated microparticles mediated by the Fc alpha/mu receptor expressed on
      pro-B cell line Ba/F3 cells. We also show that the Fc alpha/mu receptor is
      expressed in secondary lymphoid organs, such as lymph node and appendix, kidney
      and intestine, suggesting an important role of the receptor for immunity in these
      organs.

PMID- 11465088
TI  - T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ
      by endogenous tissue transglutaminase.
AB  - Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T
      cell responses to ingested wheat gliadins. Initial studies used gliadin that had
      been subjected to non-enzymatic deamidation during pepsin/trypsin digestion to
      enrich for the gliadin-specific T cells in small intestinal celiac biopsies.
      These T cells recognized synthetic gliadin peptides only after their deamidation
      in vitro by purified tissue transglutaminase (tTG). However, as these studies
      used a deamidated antigen for re-stimulation prior to testing for antigen
      specificity, this raised the possibility that T cells specific for native
      epitopes had not been expanded in vitro and had thus been overlooked. To address
      this possibility and to look for more direct evidence that endogenous tTG
      mediates deamidation of gluten in the celiac lesions, we have here used a
      minimally deamidated chymotrypsin-digest of gliadin to challenge biopsies and
      then investigated the specificity of the T cell lines derived from them.
      Interestingly, these T cell lines only barely responded to the chymotrypsin
      digested gliadins, but efficiently recognized the in vitro tTG-treated variants
      of the same gliadins. Moreover, the addition of a tTG-inhibitor during the
      gliadin challenge often resulted in T cell lines with abolished or reduced
      responses to deamidated gliadin. These data demonstrate that DQ2-restricted T
      cells within adult celiac lesions predominantly recognize deamidated gliadin
      epitopes that are formed in situ by endogenous tTG.

PMID- 11465089
TI  - Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice
      and confers susceptibility to males.
AB  - SJL (H-2s) female mice are more susceptible than males to experimental autoimmune
      encephalomyelitis (EAE) induced by immunization with myelin-derived peptides. The
      reasons for this sexual dimorphism are unclear, but may include such factors as
      sex-related differences in immune responsiveness, hormonal effects and sex-linked
      genetic factors. Recent evidence indicates that leptin modifies T cell immunity
      promoting T helper (Th) 1 pro-inflammatory immune responses. Circulating leptin
      levels show a marked sexual dimorphism, being higher in females than in males. In
      the present study, we investigated whether leptin treatment altered the course of
      relapsing-remitting EAE, induced by the proteolipid protein peptide (PLP(139
      151)), in SJL susceptible females and EAE-resistant males. Administration of
      leptin to female SJL mice before or after disease onset significantly worsened
      the disease, with a concomitant increase in the PLP(139-151)-specific delayed
      type hypersensitivity (DTH) reactivity and in vitro IFN-gamma secretion. Leptin
      treatment at priming with antigen or before disease onset rendered male SJL mice
      susceptible to EAE, with the appearance of PLP(139-151)-specific DTH reactivity
      and a switch from a Th2 to Th1 pattern of cytokine release. Our findings indicate
      that leptin administration to susceptible females resulted in a more severe
      disease, and that reduced leptin levels in male SJL mice may contribute to the
      gender-related differences in the induction phase of EAE.

PMID- 11465090
TI  - Identification of immunodominant donor MHC peptides following rejection and donor
      strain transfusion-induced tolerance of heart allografts in adult rats.
AB  - Pre-graft priming of heart allograft recipients with donor strain blood induces
      tolerance in 100% of adult rats in the congenic LEW.1W to LEW.1A combination.
      This tolerant state is specific for donor MHC antigens as third-party blood
      transfusions fail to induce tolerance, and third-party skin grafts are promptly
      rejected by tolerant graft recipients. In this study we have characterized the
      immunodominant donor (RT1u) class I and II allogenic peptides which elicit an in
      vitro proliferative response to splenocytes from recipients (RT1a) undergoing
      acute rejection or tolerant to a LEW.1A cardiac allograft. Paradoxically,
      splenocytes from tolerant animals responded more vigorously to a broader set of
      donor peptides than splenocytes from rejecting animals. In addition, several of
      these peptides were observed to be stimulatory only for tolerant splenocytes.
      These findings suggest that regulatory cells may be involved in tolerance
      induction or maintenance and are selected by specific motifs, which could be
      utilized for manipulating the immune system of graft recipients.

PMID- 11465091
TI  - Tracking the response of Xid B cells in vivo: TI-2 antigen induces migration and
      proliferation but Btk is essential for terminal differentiation.
AB  - X-linked immunodeficient (Xid) mice carry a Bruton's tyrosine kinase (Btk)
      mutation and exhibit a selective failure to produce antibodies against bacterial
      capsular polysaccharides. Studies in vitro point to a fundamental survival defect
      of Xid B cells after receptor cross-linking by thymus-independent type-2 (TI-2)
      antigen because B cells undergo apoptosis without proliferating. We describe
      results from a novel model, which we have used to investigate the impact of the
      Xid mutation on migration, proliferation and differentiation of B cells after
      polysaccharide immunization in vivo. Immunoglobulin knock-in mice, in which a
      large proportion of B cells express transgene-encoded receptors specific for (4
      hydroxy-3-nitrophenyl)-acetyl (NP), were crossed with CBA/N mice. The male
      progeny contain NP-specific Xid B cells, while the female progeny contain NP
      specific B cells with normal Btk. After immunization with the TI-2 antigen NP
      Ficoll, NP-specific Xid B cells migrate to the T zones and proliferate. Despite
      transient up-regulation of blimp-1 and survival beyond the time when terminal
      differentiation is normally underway, Btk-defective B cells fail to differentiate
      to plasmablasts or germinal center cells. CD40 ligation partially restores their
      ability to form plasma cells in response to TI-2 antigen.

PMID- 11465092
TI  - Interleukin-2 induced immune effects in human immunodeficiency virus-infected
      patients receiving intermittent interleukin-2 immunotherapy.
AB  - To characterize the immunological effects of intermittent IL-2 therapy, which
      leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11
      patients underwent extensive immunological evaluation. While IL-2 induced changes
      in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained
      increases following discontinuation of IL-2. Transient increases in expression of
      the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but
      CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This
      increase in CD25 expression was sustained for months following discontinuation of
      IL-2, and was seen in naive as well as memory cells. IL-2 induced cell
      proliferation, but tachyphylaxis to these proliferative effects developed after 1
      week despite continued IL-2 administration. It thus appears that sustained CD25
      expression selectively on CD4+ cells is a critical component of the immunological
      response to IL-2, and that intermittent administration of IL-2 is necessary to
      overcome the tachyphylaxis to IL-2-induced proliferation.

PMID- 11465093
TI  - FcgammaRIIA exogenously expressed in HeLa cells activates the mitogen-activated
      protein kinase cascade by a mechanism dependent on the endogenous expression of
      the protein tyrosine kinase Syk.
AB  - HeLa cells transfected to express the human Fc receptor FcgammaRIIA were
      stimulated with aggregates of IgG, IgG-ovalbumin equivalence immune complexes and
      monoclonal antibody reacting with FcgammaRIIA. All of these stimuli activated the
      cells as judged from the band-shift characteristic of the activation of the p42
      MAP/ERK kinase. Since this response is currently associated with the activation
      of the protein tyrosine kinase Syk, the expression of which is currently thought
      to be restricted to hemopoietic cells, the results were considered as an indirect
      evidence of the expression in HeLa cells of either Syk or another protein
      tyrosine kinase accounting for the same function. Transfection with a dominant
      negative Syk mutant abrogated the response to FcgammaRIIA cross-linking, whereas
      overexpression of Syk did not increase the extent of the response. Further
      evidence of the expression of syk was obtained by the reverse transcription PCR
      approach and sequencing of the DNA bands. Moreover, immunoprecipitation with anti
      Syk antibody of the cell lysates obtained after cross-linking of FcgammaRIIA
      followed by immunoblotting with anti-phosphotyrosine antibody showed the
      phosphorylation of a protein band migrating as Syk. These data indicate that
      expression of FcgammaRIIA on epithelial HeLa cells conveys signals to the p42
      MAP/ERK kinase by a mechanism involving the recruitment of Syk. In contrast,
      cross-linking of this receptor does not yield productive signals coupled to other
      responses associated to the FcgammaR system such as triggering of the arachidonic
      acid cascade, activation of the NF-kappaB system and production of chemotactic
      cytokines.

PMID- 11465094
TI  - Endothelial cells, megakaryoblasts, platelets and alveolar epithelial cells
      express abundant levels of the mouse AA4 antigen, a C-type lectin-like receptor
      involved in homing activities and innate immune host defense.
AB  - Phagocytic complement C1q receptor (C1qRp) and thrombomodulin (TM, CD141), are
      two key members of a novel family of lectin receptors involved in cell-cell
      interactions and innate immune host defense. We report here that the mouse
      homologue of human C1qRp (AA4) and TM are derived from a common ancestor on the
      basis that both genes co-localized to the same region of the chromosome 2 and
      also because they share similar domain composition and organization. Moreover, we
      found that mouse AA4 was localized to sites known to express TM. Mouse AA4 was
      identified by Western blot as a heavily glycosylated protein (110 kDa) expressed
      in all tissues tested. Brain and spleen expressed an additional 130-kDa band.
      Immunoperoxidase and double-immunofluorescence experiments showed that,
      surprisingly, the major site of AA4 expression in all tissue tested is on
      endothelial cells and that despite the apparent involvement of AA4 in the
      phagocytic response, it is not expressed by tissue macrophages. In contrast,
      megakaryoblasts (in bone marrow and spleen) and platelets expressed abundant
      levels of AA4 stored in cytoplasmic vesicles. Interestingly, alveolar epithelial
      cells (lung) but not other epithelia (e.g. uterus) were strongly stained for AA4.
      Although AA4 has been described on all hematopoietic progenitors, we found that
      only circulating immature B cells, monocytes and NK cells but not T cells and
      neutrophils expressed AA4.

PMID- 11465095
TI  - Activation-induced apoptosis and cell surface expression of Fas (CD95) ligand are
      reciprocally regulated by retinoic acid receptor alpha and gamma and involve
      nur77 in T cells.
AB  - It has been previously shown that CD4+ T cells enter the apoptotic suicide
      program via the Fas ligand (FasL)/Fas-mediated pathway upon T cell receptor (TCR)
      stimulation. In Jurkat cells TCR stimulation regulates the de novo synthesis of
      FasL, while in the influenza hemagglutinin-specific CD4+ murine T cell hybridoma
      (IP-12-7) the cell surface appearance of a preformed FasL is initiated. Both
      processes are dependent on new mRNA and protein synthesis, involve up-regulation
      of nur77, and can be inhibited by retinoic acids (RA). Two groups of nuclear
      receptors for RA have been identified: retinoic acid receptors (RAR) and retinoid
      X receptors (RXR). In this study various synthetic retinoids were used to define
      which receptors regulate TCR-mediated apoptosis. It is demonstrated that the
      inhibition is mediated via RARalpha, while RARgamma enhances TCR-mediated
      apoptosis, and when both receptors are stimulated, the costimulation by RXR will
      promote the effect of RARalpha. Evidence is presented that these receptors affect
      the transcriptional activity of nur77 and consequently the expression of FasL.
      Our data suggest a complex interaction between the various isoforms of retinoid
      receptors in regulating T cell death and demonstrate that the target through
      which retinoids regulate TCR-mediated apoptosis is nur77.

PMID- 11465096
TI  - Decreased generation of anti-tumor immunity after intrasplenic immunization.
AB  - The localization of antigen and the nature of the host antigen-presenting cells
      (APC) that present it to T cells are two major determinants of antigen
      immunogenicity. While lymph nodes appear to be the major site for T cell priming,
      recently the spleen was shown to provide an optimal microenvironment for direct
      CD8+ cytotoxic T cell (CTL) priming by tumor cells even in the absence of known
      costimulatory molecules on tumor cells. We analyzed whether the splenic
      microenvironment would support T cell priming also when host APC are involved
      (cross-priming) which is probably the major pathway during the generation of anti
      tumor immunity. We performed immunization/challenge experiments using different
      tumor cells (B7.1+, B7.1- and/or beta-gal+, beta-gal-) known to induce CTL to a
      variable extent either exclusively by cross-priming (B7-) or at least partially
      by direct priming (B7+). Our results demonstrate that tumor take in the spleen
      required much less cells than at a subcutaneous injection site. Additionally,
      intrasplenic immunization was invariably ineffective compared to subcutaneous
      immunization. We further showed that B cells were not responsible for the
      inefficient intrasplenic immunization. Therefore delivering the tumor cell
      antigens inside the spleen by intrasplenic immunization did not improve but
      rather decreased the efficacy of tumor cell vaccines.

PMID- 11465097
TI  - Rapid induction of CD95 ligand and CD4+ T cell-mediated apoptosis by CD137 (4
      1BB) costimulation.
AB  - We investigated the cytolytic mechanism by CD4+ T cells in anti-CD3 mAb-induced
      redirected cytotoxicity against a murine Fc receptor-bearing mastocytoma (P815)
      transfected with either CD80 or CD137 ligand (CD137L). CD137 costimulation
      preferentially induced anti-CD3-induced redirected cytotoxicity within 4 h. This
      cytotoxicity was efficiently abrogated by the addition of anti-CD137L or anti
      CD95L mAb, or by treatment with a broad caspase inhibitor, Z-VAD, suggesting that
      the induced cytotoxicity against CD137L-P815 is dependent on CD95L-mediated
      apoptosis. In contrast, the cytotoxicity against CD80-P815, but not CD137L-P815
      was efficiently inhibited by an inhibitor of perforin-dependent cytotoxicity,
      concanamycin A. Involvement of CD95L in the CD137L-dependent cytotoxicity was
      confirmed by a failure of induction of cytotoxicity by CD4+ T cells from CD95L
      gene mutated gid mice. A rapid and remarkable induction of CD95L transcription
      within 1 h was observed by CD137L costimulation. These results demonstrated that
      CD137L costimulation induces a rapid induction of CD95L on CD4+ T cells and leads
      to apoptosis of CD95-sensitive target cells. This biological function of CD137 in
      CD4+ T cells may play an important role for immune homeostasis.

PMID- 11465098
TI  - Focal adhesion kinase regulates beta1 integrin-dependent T cell migration through
      an HEF1 effector pathway.
AB  - Although beta1 integrin-dependent T cell migration is required for immune
      function, little is known of the signaling pathways regulating this migration. We
      now show that the cytoplasmic tyrosine kinase, focal adhesion kinase (FAK) plays
      an essential role in the beta1 integrin-stimulated migration of T cells through
      regulation of the unique Crk-associated substrate (Cas) family docking protein,
      human enhancer of filamentation 1 (HEF1) and effects on "outside-in" beta1
      integrin signaling. Overexpression of wild-type FAK promoted beta1 integrin
      dependent Jurkat T cell migration, whereas FAK mutated in either its
      autophosphorylation site or proline rich region 1 (PR1)/HEF1 SH3 domain-binding
      site had a dominant negative effect on migration. In contrast, neither wild-type
      nor mutant FAK affected Jurkat cell adhesion to fibronectin, a beta1 integrin
      ligand. The migration of FAK-overexpressing cells directly correlated with the
      beta1 integrin-inducible tyrosine phosphorylation of endogenous plus wild-type
      exogenous FAK, and not with phosphorylation of the FAK-related kinase, Pyk2. FAK
      was also found to regulate both HEF1-promoted migration, and HEF1 tyrosine
      phosphorylation in beta1 integrin-stimulated cells, in a manner dependent upon
      the FAK autophosphorylation and PR1 sites, and HEF1 SH3 domain. Together, our
      results indicate that beta1 integrin-stimulated T cell migration requires a
      linear beta1 integrin-FAK-HEF1 effector pathway.

PMID- 11465099
TI  - ULBP1, 2, 3: novel MHC class I-related molecules that bind to human
      cytomegalovirus glycoprotein UL16, activate NK cells.
AB  - New members of the extended MHC class I-like family were identified based on
      their ability to bind human cytomegalovirus glycoprotein UL16 and/or their mutual
      homology. Soluble UL16 binding proteins (ULBP) competed with each other for
      binding to NK cells. Treatment of human and mouse NK cells with ULBP led to
      increased production of cytokines/chemokines, proliferation, cytotoxic activity
      and up-regulation of activation-associated surface molecules. The presence of
      ULBP during the stimulation phase of the CTL assay caused increased cytotoxic
      activity. Addition of soluble recombinant UL16 protein inhibited the biological
      activities mediated by ULBP, suggesting the existence of a novel mechanism
      utilized by CMV to evade elimination by the host immune system.

PMID- 11465100
TI  - Characterization of novel HLA-DR11-restricted HCV epitopes reveals both
      qualitative and quantitative differences in HCV-specific CD4+ T cell responses in
      chronically infected and non-viremic patients.
AB  - The CD4+ T cell response is of critical importance in determining the fate of
      many viral infections. Clearance of HCV has a strong association with the MHC
      class II antigen HLA-DR11 suggesting a key role for CD4+ T cells. We used an
      epitope-prediction program to identify multiple novel HLA-DR11-restricted
      epitopes derived from several HCV proteins. These epitopes then allowed us to
      explore the qualitative and quantitative aspects of specific CD4+ T cell
      responses in HLA-DR11+ patients. Irrespective of the time since viral clearance,
      all the non-viremic patients recognized four epitopes with a high frequency of
      IFN-gamma-producing memory CD4+ T cells. There appeared to be two subpopulations
      of memory cells, immediate "effector" memory cells (Th1 phenotype) and resting
      "central" memory cells (Th1/0). Chronically infected patients revealed an almost
      complete absence of HCV epitope-specific IFN-gamma-producing T cells. However,
      three of these epitopes induced IL-10 production (down-regulatory) raising the
      question as to whether these cells play a role in viral persistence. The
      frequency and phenotype of memory cells is likely to reflect the magnitude of the
      initial immune response, and suggests that a high frequency of IFN-gamma
      secreting CD4+ T cells to multiple epitopes are important in clearance of HCV.

PMID- 11465101
TI  - Identification of two liver proteins recognized by autoantibodies elicited in
      mice infected with mouse hepatitis virus A59.
AB  - Western blot experiments showed that sera from mice infected with the mouse
      hepatitis virus strain A59 (MHV-A59) contained autoantibodies (autoAb) that bound
      to a 40-kDa protein present in liver and kidney extracts. No reaction was
      observed with extracts of the heart, muscles, spleen, brain and lung. The Ab
      cross-reacted with a 40-kDa protein from human, rat and sheep liver, but not with
      liver extracts from the silver side fish (Odontesthes bonariensis). No
      correlation was found between the development of the hypergammaglobulinemia that
      followed the viral infection and the occurrence of the autoAb. Reactive
      immunoglobulins pertained to the IgG1, IgG2a and IgG2b subclasses, recognized
      cryptic epitopes and were detected from 10 days up to 8 weeks after MHV
      infection. The 40-kDa protein was purified from mouse liver extracts by ion
      exchange chromatography, gel filtration and SDS-PAGE. Because the N-terminal was
      blocked, we digested the protein in-gel with trypsin and sequenced various
      peptides. Results indicated a 100% homology of sequence between the protein
      recognized by the autoAb and liver fumarylacetoacetate hydrolase (FAH), the
      enzyme that mediates the last step of tyrosine catabolism. Additionally, a second
      protein recognized by the autoAb was detected during FAH purification steps and
      was identified as liver alcohol dehydrogenase.

PMID- 11465102
TI  - CD28 costimulation is required not only to induce IL-12 receptor but also to
      render janus kinases/STAT4 responsive to IL-12 stimulation in TCR-triggered T
      cells.
AB  - The activation of resting T cells for the acquisition of various functions
      depends on whether CD28 costimulatory signals are provided upon T cell receptor
      stimulation. Here, we investigated how CD28 costimulation functions to allow TCR
      triggered resting T cells to acquire IL-12 responsiveness. When T cells are
      stimulated with low doses of anti-CD3 mAb, CD28 costimulation was required for
      the optimal levels of IL-12 receptor (IL-12R) expression. However, stimulation of
      T cells with high doses of anti-CD3 alone induced comparable levels of IL-12R
      expression to those induced upon CD28 costimulation. Nevertheless, there was a
      substantial difference in IL-12 responsiveness between these two groups of T
      cells: compared to anti-CD28-costimulated T cells, T cells that were not
      costimulated with anti-CD28 exhibited decreased levels of Janus kinases (JAK)
      JAK2/TYK2 and STAT4 phosphorylation and IFN-y production following IL-12
      stimulation. Importantly, STAT6 phosphorylation following IL-4 stimulation was
      not decreased in anti-CD28-uncostimulated T cells. These resutls indicate that
      CD28 costimulation not only contributes to up-regulating IL-12R expression but is
      also required to render JAKs/STAT4 responsive to IL-12 stimulation.

PMID- 11465103
TI  - Characterization of chemokines and chemokine receptors in two murine models of
      inflammatory bowel disease: IL-10-/- mice and Rag-2-/- mice reconstituted with
      CD4+CD45RBhigh T cells.
AB  - We used quantitative PCR to investigate the expression of chemokines and
      chemokine receptors in two Th1-mediated murine models of inflammatory bowel
      disease (IBD). First, mRNA levels encoding the chemokines MIG, RANTES,
      lymphotactin, MIP-3alpha, TCA-3, TARC, MIP-3beta, LIX, MCP-1 and MIP-1beta and
      the receptors CCR4, CCR6 and CCR2 were significantly increased in chronically
      inflamed colons of IL-10-/- mice when compared with wildtype mice. Interestingly,
      reversal of colitis in IL-10-/- mice by anti-IL-12 mAb was accompanied by the
      inhibition in the expression of LIX, lymphotactin, MCP-1, MIG, MIP-3alpha, MIP
      3beta, TCA-3, CCR2 and CCR4, whereas the increased mRNA levels of MIP-1beta,
      RANTES, TARC and CCR6 were unaffected. Second, to investigate which chemokines
      and receptors were up-regulated during the inductive phase of colitis, we
      employed the CD4+CD45RBhigh T cell transfer model. At 4 and 8 weeks after
      reconstitution of Rag-2-/- mice the mRNA levels of IP-10, MCP-1, MDC, MIG, TARC,
      RANTES, CCR4 and CCR5 were significantly increased prior to the appearance of
      macroscopic lesions. Other chemokines and chemokine receptors were clearly
      associated with the acute phase of the disease when lesions were evident. The sum
      of our studies with these two models identifies chemokines that are expressed at
      constant levels, irrespective of inflammatory responses, and those that are
      specifically associated with acute and/or chronic stages of Th1-driven colitis.

PMID- 11465104
TI  - Toxoplasma gondii down-regulates MHC class II gene expression and antigen
      presentation by murine macrophages via interference with nuclear translocation of
      STAT1alpha.
AB  - The obligate intracellular protozoan parasite Toxoplasma gondii is able to
      establish persistent infections within human and animal hosts. We have shown
      recently that T. gondii down-regulates IFN-gamma-induced MHC class II expression
      in murine bone marrow-derived macrophages (BMM4). As shown in this study, the
      capacity of IFN-gamma-activated murine BMMphi to present ovalbumin to CD4+ T cell
      hybridomas was dose-dependently inhibited by T. gondii. IFN-gamma-induced up
      regulation of H2-Aa, H2-Ab, H2-Eb, H2-Ma, H2-Mb, H2-Oa and invariant chain
      transcripts was prominently down-regulated by T. gondii. Furthermore, mRNA levels
      of class II transactivator and interferon-regulatory factor-1 were significantly
      diminished. Electromobility shift assays demonstrated a decrease in the binding
      activity of nuclear extracts to the IFN-gamma-activated site after infection with
      T. gondii, indicating parasitic interference with IFN-gamma-induced signaling.
      However, neither the expression of the IFN-gammaR nor the IFN-gamma-induced
      tyrosine phosphorylation of IFN-gammaR alpha chain and signal transducer and
      activator of transcription (STAT) 1alpha was diminished by T. gondii. IFN-gamma
      induced nuclear translocation of STAT1alpha was nevertheless inhibited after
      infection as demonstrated by immunofluorescence microscopy and subcellular
      fractionation analyses. In conclusion, this novel mechanism of microbial
      interference with MHC class II gene expression may contribute to intracellular
      survival and establishment of persistent infection with T. gondii.

PMID- 11465105
TI  - In vivo MHC class II presentation of cytosolic proteins revealed by rapid
      automated tandem mass spectrometry and functional analyses.
AB  - We report a strategy for high through-put sequence analyses of large MHC class II
      bound peptide repertoires which combines automated electrospray ionization tandem
      mass-spectrometry with computer-assisted interpretation of the tandem mass
      spectra using the algorithm SEQUEST. This powerful approach discerned 128 peptide
      sequences displayed by the murine MHC class II molecule I-Ab in activated B cells
      and macrophages, including a surprisingly large number of peptides derived from
      self cytosolic proteins. Mice lacking the chaperone molecule H-2M were used to
      generate T cells specific for selected self peptides. Functional T cell analyses
      of ex vivo antigen-presenting cells indicated that peptides originating from
      cytosolic proteins are efficiently presented by splenic and thymic dendritic
      cells, but less so by resting B cells or thymic cortical epithelial cells. These
      results suggest that central tolerance to at least some MHC class II-bound self
      peptides derived from cytosolic proteins exists in vivo.

PMID- 11465106
TI  - Defective in vivo induction of functional type 2 cytokine responses in aged mice.
AB  - Aged mice have various defects in their immune system. We report that following
      in vivo challenge with type 2 cytokine-inducing Schistosoma mansoni eggs, aged
      mice fail to produce type 2 cytokines and also have impaired antigen-specific
      antibody production. Using two separate type 2 cytokine-dependent in vivo models,
      the synchronous pulmonary schistosome egg granuloma model and infection with the
      gastro-intestinal nematode Nippostrongylus brasiliensis, aged mice were shown to
      have a dramatically impaired capacity to elicit a functional type 2 response, i.
      e. respectively, impaired pulmonary granulomas and delayed rejection of
      intestinal worms. Aged mice did not develop eosinophilia and had impaired
      production of antigen specific IgE. Defective induction of type 2 responses was
      associated with negligible IL-2 and elevated IFN-gamma production by cells from
      aged mice. Naive aged mice had increased numbers of Th1, Th2 and Tc1 cells
      compared to young animals. In vivo type 2 challenge increased the frequencies of
      Th1 and Tc1 cells and reducing Th2 cell numbers in aged mice. These data
      demonstrate that a consequence of ageing is a profound in vivo defect in the
      capacity to elicit type 2 cytokine responses and such an impairment in type 2
      responsiveness may account for the increased incidence of various type 1 cytokine
      mediated diseases in aged individuals.

PMID- 11465107
TI  - Trypanosoma cruzi trans-sialidase potentiates T cell activation through antigen
      presenting cells: role of IL-6 and Bruton's tyrosine kinase.
AB  - Polyclonal lymphocyte activation and hypergammaglobulinemia characterize the
      acute phase of Chagas' disease, a debilitating condition caused by Trypanosoma
      cruzi. Such pathogenic hyper-reactivities not only compromise specific host
      defense against the pathogen, but may also contribute to infection-induced
      chronic autoimmune responses. Recent studies showed that T. cruzi trans-sialidase
      (TS) directly stimulates the polyclonal proliferation and Ig secretion of normal
      murine B cells in a T-independent, Bruton's tyrosine kinase (Btk)-dependent
      manner. Related to this observation, we now show that parasite-derived and
      recombinant TS potentiate the proliferation and cytokine secretion of normal T
      cells triggered by antigen-specific and non-specific stimuli. TS potentiates T
      cell activation through stimulating B cells and macrophages, independent of
      CD40/CD40L and CD43 pathways. In contrast, optimal TS potentiation requires
      interleukin-6 (IL-6) and Btk, as it is significantly reduced in splenocytes from
      IL-6-/- and Btk-defective Xid mice. The results suggest that TS, directly and
      indirectly, activates both antigen-presenting cell and T cell compartments, and
      that TS-induced IL-6 may further amplify such activation. These observations open
      up the possibility that TS drives the polyclonal lymphocyte activation in acute
      T. cruzi infection, a phenomenon contributing to the pathogenesis of Chagas'
      disease.

PMID- 11465108
TI  - Identification of Chlamydia trachomatis antigens recognized by human CD4+ T
      lymphocytes by screening an expression library.
AB  - Identification of the immunogenic proteins that induce Chlamydia trachomatis (CT)
      specific T cell responses is crucial to the development of protective vaccines
      and understanding the mechanisms of chlamydia-induced pathology. To characterize
      the targets of the human T cell response we have used chlamydia-reactive human T
      cell clones as cellular probes to screen a CT genomic library expressed in
      Escherichia coli using peripheral blood mononuclear cells to present antigens.
      The library was screened with three chlamydia-reactive T cell clones of unknown
      specificity and three novel stimulatory chlamydia antigens were identified. These
      E. coli recombinants were shown to express the chlamydia proteins, enolase, pmpD
      and CT579. Enolase and pmpD proteins were purified and shown to induce the
      proliferation of synovial fluid mononuclear cells isolated from the knee joints
      of patients suffering from chlamydia-associated reactive arthritis. We suggest
      that these stimulatory antigens are common targets of the T cell response in this
      group of patients. A greater understanding of T cell-mediated immunity in
      uncomplicated CT infection, and in patients with CT-induced chronic inflammatory
      disease (trachoma, salpingitis, arthritis) may identify the principal immune
      responses associated with immunopathology.

PMID- 11465109
TI  - Expression of the DX5 antigen on CD8+ T cells is associated with activation and
      subsequent cell death or memory during influenza virus infection.
AB  - The antigen recognized by the DX5 antibody (DX5 antigen) is expressed on all
      murine NK cells. In the present study we found that a proportion of CD8+ T cells
      (approximately 5%) also express the DX5 antigen in uninfected mice, and that
      numbers of CD8+ T cells expressing DX5 are significantly higher in the lungs of
      influenza virus-infected mice representing up to 50% of all CD8+ T cells on day
      10 post infection. The expression of the DX5 antigen on CD8+ T cells was
      associated with a memory phenotype in uninfected C57BL/6 mice and with an
      activation phenotype during influenza virus infection. Interestingly, when
      lymphocytes were isolated from lungs of influenza virus-infected mice on day 10
      post infection and adoptively transferred into recombination activating gene-1
      (RAG1)-deficient mice, CD8+DX5+ cells could not be recovered from the recipient
      mice 2 days later. Moreover, CD8+DX5+ cells were not detected when lung cells
      were removed from day 10 influenza virus-infected mice and cultured in vitro for
      2 days. However, CD8+DX5+ cells could be detected when apoptosis inhibitors were
      added to these cultures, suggesting that the CD8+DX5+ cells underwent apoptosis
      during cell culture. Furthermore, almost all DX5 expressing CD8+ cells from lungs
      of mice on day 10 post influenza virus infection stained positively with Annexin
      V. Taken together, the data suggest that CD8+ T cells expressing DX5 are
      associated with an activation/memory phenotype and are biased towards apoptosis.

PMID- 11465110
TI  - Neonatal bacillus Calmette-Guerin vaccination induces adult-like IFN-gamma
      production by CD4+ T lymphocytes.
AB  - The immaturity of the neonatal immune system in mice is associated with defective
      IFN-gamma production and Th2-biased immune responses. In this study, infants
      vaccinated at birth with BCG produced similar concentrations of IFN-gamma in
      response to PPD and showed similar frequencies of IFN-gamma-producing lymphocytes
      as compared to immune adults. Infants and adults produced only low concentrations
      of IL-4 and IL-5. CD4+ T lymphocytes were the main source of IFN-gamma. Similar
      proportions of Th1 and Th0 PPD-specific T cell clones were observed in infants
      and adults. This study demonstrates that the human neonatal immune response to
      BCG is not biased towards Th2 and is characterized by the predominant production
      of IFN-gamma by CD4+ T lymphocytes.

PMID- 11465111
TI  - Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates
      neutrophil migration by modulating CXCR-1 expression.
AB  - CD28, described as a T cell costimulatory molecule so far, is expressed on human
      peripheral blood neutrophils, as shown by cell surface staining and
      immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse
      transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of
      CD28 on these cells can be blocked by actinomycin D, an RNA transcription
      inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28
      results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and
      a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is
      down-regulated by receptor internalization 3 h after CD28 cross-linking with
      concurrent decrease in IL-8-induced chemotactic migration. Thus, our results
      demonstrate for the first time that CD28 is expressed on human peripheral blood
      neutrophils and that CD28 may play an important role in the regulation of IL-8RA
      expression and migration of neutrophils in response to IL-8.

PMID- 11465112
TI  - BLC (CXCL13) is expressed by different dendritic cell subsets in vitro and in
      vivo.
AB  - Dendritic cells (DC) attract both T and B lymphocytes to induce an efficient
      antigen-specific immune response. Recently, it was shown that naive T cells are
      attracted to DC by dendritic cell chemokine 1 (DC-CK1, CCL18). The potent B
      lymphocyte chemoattractant BLC (CXCL13) was previously shown to be essential for
      homing of lymphocytes into secondary lymphoid organs and for the development of B
      cell follicles. As the cells that produce BLC are largely unknown and BLC could
      be a candidate chemokine for the recruitment of B cells to DC, we analyzed
      different DC subsets for expression of BLC. Here we demonstrate that monocyte
      derived DC as well as activated blood DC indeed express and secrete BLC.
      Interestingly, ligation of the CD40 molecule down-regulated BLC expression in
      monocyte-derived DC. Staining of tonsilar sections indicated that BLC is
      expressed by follicular dendritic cells and germinal center dendritic cells
      (GCDC) in vivo. Real-time quantitative PCR confirmed the expression of BLC in
      isolated GCDC. Since both B cells and activated T cells express the receptor for
      BLC, our findings implicate an important role for BLC in establishing the
      interaction of DC with T cells and B cells. Furthermore, CD40/CD40 ligand
      interactions could modulate this process by down-regulating the expression of
      BLC.

PMID- 11465113
TI  - Role of interleukin-12 in the induction of mucosal inflammation and abrogation of
      regulatory T cell function in chronic experimental colitis.
AB  - IL-12 promotes Th1 cell differentiation and cell-mediated immunity. In the
      present study, the potential role of IL-12 was analyzed in an experimental
      colitis model in scid mice reconstituted with syngeneic CD45RBhighCD4+ T cells.
      Real-time reverse transcription-PCR studies demonstrated that IL-12 p40 mRNA in
      inflamed colon is induced shortly after T cell transfer and maintained at a
      stable level after week 4, at the time when wasting disease starts.
      Administration of anti-IL-12 on days 0,14, and 28 (early treatment) or on days
      28, 42, and 56 (delayed treatment) after T cell transfer, effectively prevented
      or, respectively cured wasting disease and colitis in scid recipients. Anti-IL-12
      treatment abrogated mucosal inflammation with significantly diminished leukocyte
      infiltration (CD4 cells, macrophages) and CD54 expression, and down-regulated
      proinflammatory cytokines IFN-gamma and IL-2. Of note, although splenic CD4+ T
      cells are unable to induce disease as a result of the presence of regulatory
      CD45RBlow cells, splenic CD4+ T cells, preactivated by IL-12 and anti-CD3 in
      vitro, were highly pathogenic in inducing severe mucosal inflammation, suggesting
      that IL-12 and anti-CD3 abrogated regulatory T cell function. These findings
      indicate that IL-12 is important for the induction of experimental colitis
      through effects on proinflammatory cytokine production and on regulatory T cell
      function.

PMID- 11465114
TI  - CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts
      in rafts.
AB  - To investigate the role of the coreceptor CD8 and lipid rafts in cytotoxic T
      lymphocyte (CTL) activation, we used soluble mono-and multimeric H-2Kd-peptide
      complexes and cloned S14 CTL specific for a photoreactive derivative of the
      Plasmodium berghei circumsporozoite (PbCS) peptide 252-260 [PbCS(ABA)]. We report
      that activation of CTL in suspension requires multimeric Kd-PbCS(ABA) complexes
      co-engaging TCR and CD8. Using TCR ligand photo-cross-linking, we find that
      monomeric Kd-PbCS(ABA) complexes promote association of TCR/CD3 with CD8/p56lck.
      Dimerization of these adducts results in activation of p56lck in lipid rafts,
      where phosphatases are excluded. Additional cross-linking further increases
      p56lck kinase activity, induces translocation of TCR/CD3 and other signaling
      molecules to lipid rafts and intracellular calcium mobilization. These events are
      prevented by blocking Src kinases or CD8 binding to TCR-associated Kd molecules,
      indicating that CTL activation is initiated by cross-linking of CD8-associated
      p56lck. They are also inhibited by methyl-beta-cyclodextrin, which disrupts rafts
      and by dipalmitoyl phosphatidylethanolamine, which interferes with TCR signaling.
      Because efficient association of CD8 and p56lck takes place in rafts, both
      reagents, though in different ways, impair coupling of p56lck to TCR, thereby
      inhibiting the initial and essential activation of p56lck induced by cross
      linking of engaged TCR.

PMID- 11465115
TI  - The protein tyrosine kinase syk activity is reduced by clustering the mast cell
      function-associated antigen.
AB  - The mast cell function-associated antigen (MAFA) is a glycoprotein first
      identified on the membrane of rat mucosal-type mast cells (RBL-2H3 line). MAFA
      clustering causes a dose-dependent inhibition of these cells' secretory response
      to the type I Fcepsilon receptor (FcepsilonRI) stimulus. The inhibition has
      earlier been shown to take place upstream to the production step of inositol
      phosphates in the FcepsilonRI coupling cascade. To resolve further the mechanism
      of action of MAFA, we have investigated the events prior to the activation of
      phospholipase C. Activities of the non-receptor protein tyrosine kinases Lyn and
      Syk in untreated cells were compared with those where the FcepsilonRI, MAFA or
      both were clustered. Syk tyrosine phosphorylation and activation, as well as LAT
      (linker for activation of T cells) tyrosine phosphorylation, both induced by
      FcepsilonRI clustering, were found to be reduced upon MAFA clustering. In
      contrast, the activity of the Src homology domain 2 (SH2)-containing protein
      tyrosine phosphatase (SHP-2) increased. MAFA clustering also enhanced the co
      isolation of SHP-2 and Syk with tyrosine-phosphorylated MAFA in both untreated
      and FcepsilonRI-stimulated cells. SHP-2 caused a decline in the FcepsilonRI
      induced tyrosine phosphorylation of Syk, at least under in vitro conditions.
      Taken together, these results suggest that one possible mechanism by which MAFA
      affects the FcepsilonRI stimulation cascade is suppression of Syk activity, i.e.
      MAFA clustering leads SHP-2 to act on Syk, thereby reducing its tyrosine
      phosphorylation and its activity.

PMID- 11465116
TI  - Reversal of established delayed type hypersensitivity reactions following therapy
      with IL-4 or antigen-specific Th2 cells.
AB  - Delayed-type hypersensitivity reactions (DTHR) are mediated by IFN-gamma
      producing CD4+ (Th1) or CD8+ T cells (Tc1) and can be prevented by steering T
      cells toward an IL-4-producing Th2 or Tc2 phenotype. It is currently accepted
      that T cells can be directed toward a Th2 or Tc2 phenotype only during the
      initiation of an immune response. Once established, the cytokine pattern of
      immune reactions is believed to be stable. Therefore, inhibition of DTHR by the
      induction of Th2/Tc2 responses, termed immune deviation, is considered only as a
      prevention but not as a therapy of harmful DTHR. Here we demonstrate that
      therapeutic immune deviation can reverse established contact hypersensitivity
      (CHS), a Th1/Tc1-mediated DTHR. One or two weeks after induction of CHS, mice
      received either a single cycle of IL-4 therapy or adoptive transfer of antigen
      specific Th2 cells. This treatment generated a novel state of immunity that
      provided long-lasting protection against tissue destruction and neutrophil
      recruitment during subsequent antigen exposures. Therapeutic immune deviation of
      established CHS was dependent on CD4+ T cells and the induction of endogenous IL
      4 synthesis. Thus, a population of immunoregulatory Th2 cells persists during
      advanced inflammatory responses that can be used for therapeutic deviation of
      established DTHR.

PMID- 11465117
TI  - Individual cathepsins degrade immune complexes internalized by antigen-presenting
      cells via Fcgamma receptors.
AB  - We have analyzed the intracellular degradation of an immune complex after its
      FcgammaR-mediated uptake in antigen-presenting cells (APC). Mice that lack the
      cathepsins (Cat) S, L, B and D allowed us to assess the direct contribution of
      these individual proteases to the processing events observed. CatS and CatB
      mediate the bulk of degradation of the Ig-125I-labeled F(ab')2 immune complex
      delivered via FcgammaR, while CatL and CatD are dispensable. CatS and CatB are
      involved in independent processing pathways and can substitute in part for each
      other's absence. The combined ablation of both proteases reduces the rate of
      degradation observed by > 80 %. CatB is required for the generation of F(ab')23,
      a predominant degradation intermediate smaller by approximately 3 kDa than the
      125I-labeled F(ab')2 itself. In addition, absence of CatB in vivo significantly
      affects the activity pattern of the remaining cysteine proteases. Thus, we
      conclude that CatB is a key enzyme for the proper degradation of an immune
      complex taken up by FcgammaR and for the control of protease activity in the
      endocytic pathway of APC.

PMID- 11465118
TI  - The role of heat shock protein (hsp70) in dendritic cell maturation: hsp70
      induces the maturation of immature dendritic cells but reduces DC differentiation
      from monocyte precursors.
AB  - Members of the heat shock protein (hsp70) family are either constitutively
      expressed (hsc70) or can be induced by hyperthermic stress (hsp70). Recombinant
      hsp70 (rhsp70) stimulates cytokine production from monocytes and enhances NK cell
      proliferation and cytotoxicity. Here we demonstrate that rhsp70 binds to immature
      dendritic cells (DC) derived from monocyte precursors and induces their
      maturation as evidenced by an increase in CD40, CD86 and CD83 expression.
      Immature DC stimulated to mature with rhsp70 show an enhanced ability to present
      tyrosinase peptide to specific CTL. Mature DC did not bind rhsp70, suggesting a
      down-regulation in the expression of its receptor. When rhsp70 was added to
      monocyte precursors at the same time as GM-CSF and IL-4 it reduced the
      differentiation of monocytes into DC as shown by a decrease in the level of CD40,
      CD83, CD86 and HLA-DR expression and an increase in CD14 expression. The
      constitutively expressed hsc70 had neither a stimulatory effect on the maturation
      of immature DC nor did it reduce the differentiation of monocytes into DC. These
      findings demonstrate the specific ability of rhsp70 to induce the maturation of
      immature DC. Therefore rhsp70 may be useful for its adjuvant like properties in
      DC based immunotherapy of certain tumors.

PMID- 11465119
TI  - Regulation by rho family GTPases of IL-1 receptor induced signaling: C3-like
      chimeric toxin and Clostridium difficile toxin B inhibit signaling pathways
      involved in IL-2 gene expression.
AB  - In this study the participation of Rho family GTPases in the regulation of IL-1
      activated protein kinase cascades controlling IL-2 synthesis was investigated in
      murine EL-4 thymoma cells. The recombinant C3-like chimeric toxin, which consists
      of the C3 toxin of Clostridium limosum and the N-terminal part of Clostridium
      botulinum C2 toxin (C2IN-C3) interacting with the C2II binding subunit to
      facilitate uptake into cells, and selectively inactivates Rho A by ADP
      ribosylation, prevented IL-1-stimulated activation of Jun-NH2-terminal-kinases
      (JNK) and p38 mitogen-activated-protein kinases (MAPK). UDP-monoglucosylation and
      concomitant inactivation of Rho A and of Rac-2 by Clostridium difficile toxin B
      also inhibited IL-1-induced activation of JNK and p38 MAPK, but additionally
      inhibited activation of the extracellular-regulated-kinase pathway and DNA
      binding of the transcription factor NFkappaB. Accordingly, pre-treatment of cells
      with C21N-C3 fusion toxin only decreased IL-1-stimulated IL-2 synthesis by 50%,
      while in C. difficile toxin B-treated cells IL-1-induced IL-2 secretion was
      reduced by 90%. These results imply that together with Rho A an additional member
      of the Rho family G proteins, i.e. Rac-2, is critically involved as an upstream
      regulator in IL-1-induced activation of different MAPK, stress-activated protein
      kinases, and in NFkappaB activation controlling IL-2 gene expression in response
      to IL-1, acting in close proximity to the IL-1-receptor complex.

PMID- 11465120
TI  - Differential activation of human gammadelta cells by nonpeptide phosphoantigens.
AB  - Human T cells expressing Vgamma9Ndelta2-encoded TCR recognize several nonpeptide
      phosphoantigens in the absence of major histocompatibility complex restriction.
      As these cells respond differentially to increasing concentrations of
      structurally related phosphoantigens, such ligands constitute agonists of
      different strengths. By analyzing early cellular events and late effector
      responses of gammadelta T cells, we compared their patterns of stimulation by
      weak, medium and strong phosphoantigen agonists. We found that, although the
      early metabolic activation as assessed by cytosensor microphysiometry directly
      reflects the intensity of subsequent effector response by gammadelta cells, TCR
      down-modulation is dissociated from the latter. Weak and mid-range phosphoantigen
      agonists induce a time- and dose-dependent down-modulation of the gammadelta TCR,
      whereas strong phosphoantigen agonists induce little or no TCR down-regulation.
      This indicates that gammadelta TCR down-modulation does not match the extent of
      TCR signaling as assessed by microphysiometry or conventional effector responses
      (TNF-alpha production and cytotoxicity). This differential pattern of gammadelta
      cell activation by phosphoantigens could explain the stronger potencies of some
      of these agonists.

PMID- 11465121
TI  - Injuries to the toes and metatarsals.
AB  - Traumatic injuries to the toes and metatarsals are common injuries affecting
      nearly every individual. Injuries may be precipitated by industrial accidents or
      simple bumps in the night. They can produce a wide spectrum of consequences
      ranging from permanent disability to asymptomatic deformities. With appropriate
      treatment, most individuals should have the capacity to return to their preinjury
      functional status.

PMID- 11465122
TI  - Foot compartment syndrome.
AB  - FCS is a recognized clinical entity that has few consistent clinical signs except
      tense swelling. A high degree of clinical suspicion is necessary to provide
      appropriate treatment. Invasive direct pressure monitoring is needed to diagnose
      FCS. High-energy injuries are known to cause FCS, but individual risk factors,
      such as prolonged venous occlusion and blood dyscrasias, are causative factors.

PMID- 11465123
TI  - Developments and advances in the diagnosis and treatment of injuries to the
      tarsometatarsal joint.
AB  - Continued research and clinical advances have allowed clinicians to diagnose
      injuries of the tarsometatarsal joint earlier and with greater precision than in
      previous eras and have promoted refinements of the surgical procedures used in
      their treatment. For patients with such injuries, these advances should result in
      improved function and a substantial decrease in morbidity.

PMID- 11465124
TI  - Complications of ankle fractures in diabetic patients.
AB  - Ankle fracture in patients with DM mandates a stepwise protocol to minimize the
      potential complications of delayed fracture healing, wound complications, and
      development of Charcot arthropathy. For nondisplaced ankle fracture, a
      nonoperative approach with increased duration of immobilization seems successful
      based on experience of the limited series. A displaced ankle fracture in a
      patient with DM requires a surgical intervention. The authors advocate tight
      glucose control in both groups to improve the fracture milieu and to ameliorate
      the potential complications. Appropriate stable fixation with adequate length of
      immobilization is crucial for successful fracture resolution.

PMID- 11465125
TI  - Soft tissue reconstruction for calcaneal fractures or osteomyelitis.
AB  - A systematic approach of the surgical management of a calcaneal fracture can
      minimize the potential of soft tissue complications. When reducing a closed
      calcaneal fracture, the incision used affects the postoperative complications.
      The L-shaped incision with the horizontal limb lying on the lateral glabrous
      junction ensures maximum blood flow to either side of the incision. Whether or
      not the wound can be closed primarily depends on the preexisting edema, the lost
      calcaneal height, and the delay between the fracture and reduction (Fig. 20). The
      wrinkle test is a good indicator that the incision can be closed primarily if the
      amount of height restored is minimal. If the edema is too great, steps should be
      taken to reduce it sufficiently to allow successful wound closure. If the wound,
      after reduction, is too wide to allow primary closure, an ADM flap laterally or
      an AHM flap medially should be used. For larger defects, a free flap should be
      considered. The three important steps to reconstruction of soft tissue defects
      around the calcaneus include good blood supply, a infection-free wound, and the
      simplest soft tissue reconstructive option that covers the wound successfully.
      Adequate blood supply can be determined by the use of Doppler. If the supply is
      inadequate, revascularization is necessary before proceeding. Achieving a clean
      wound requires aggressive debridement, intravenous antibiotics, and good wound
      care. Adjuncts that can help in achieving a clean wound include topical
      antibiotics (silver sulfadiazine), the VAC, and hyperbaric oxygen. Osteomyelitis
      has to be treated aggressively. Any suspicious bone has to be removed. Only
      clean, healthy, bleeding bone is left behind. Antibiotic beads can be useful when
      there is doubt as to whether the cancellous bone is infection-free. The beads are
      not a substitute for good debridement, however. Soft tissue reconstruction ranges
      from delayed primary closure to the use of microsurgical free flaps (Fig. 21).
      When bone or hardware is exposed, a muscle flap should cover the wound because of
      the extra blood supply it carries with it. The soft tissue option depends on the
      width of the wound. For wounds 1 cm wide or less, the options include allowing
      the wound to close by secondary intention (VAC), delayed primary closure, or a
      local muscle flap. For wounds 2 cm wide or less, allowing the wound to close by
      secondary intention (VAC) and a local muscle flap are the best options. For wider
      wounds, one has to assess whether the local muscle flap has sufficient bulk to
      close the defect. If it does, it is the simplest solution. If the local muscle is
      inadequate, a microsurgical free flap has to be used. The VAC sometimes can
      convert a large wound to a smaller wound so that a local muscle flap can be used.
      This procedure takes time, however, and adds to the cost of the repair.

PMID- 11465126
TI  - Fractures of the base of the fifth metatarsal: the Jones fracture.
AB  - The Jones fracture continues to be a problem fracture for the orthopedic surgeon
      and sports medicine physician. This injury seems to occur in athletes as well as
      nonathletes. The underlying inherent poor blood supply of the proximal
      metaphyseal diaphyseal region makes the fifth metatarsal a difficult bone to
      unite. Many techniques have been advocated for the treatment of this troublesome
      fracture, including non-weight-bearing short leg casting, orthotic management,
      open reduction and internal fixation, corticocancellous onlay bone grafting, and
      electric stimulation. The author believes that in young athletic patients, using
      meticulous surgical technique, reliable open reduction and internal fixation
      yields excellent results. In nonathletic or less demanding patients, the patient
      should participate in the discussion and choice of the treatment techniques. If
      delayed union or non-union occurs, drilling with the use of internal fixation
      usually produces a union.

PMID- 11465127
TI  - Salvage or amputation after complex foot and ankle trauma.
AB  - A treating surgeon must take all the aforementioned ideas and principles into
      consideration, make a reasoned decision in the first hour of patient evaluation,
      and proceed with the chosen treatment. When functional salvage is not thought to
      be possible, it is better simply to let the patient and family know, then proceed
      directly to the best possible reconstructive amputation. This approach saves the
      patient, family, friends, and treatment team an enormous amount of anguish and
      allows for the earliest possible acceptance and positive approach to
      rehabilitation.

PMID- 11465128
TI  - Wound-healing risk factors after open reduction and internal fixation of
      calcaneal fractures: does correction of Bohler's angle alter outcomes?
AB  - The study reviewed in this article evaluated a group of patients who underwent
      surgical therapy for calcaneal fractures at a Level I trauma center. One group of
      patients was treated after outpatient referral to the center, whereas the other
      group was admitted to, and underwent surgery at, the center. This study attempted
      to determine which patient risk factors or injury characteristics might lead to
      an increased rate of wound-healing complications. Bohler's angle is a classic
      radiographic method of determining the severity of calcaneal injury in this group
      of patients. The question posed by the authors of this study was: Does a drastic
      correction in Bohler's angle lead to an increased incidence of wound-healing
      complications? The authors do not recommend undercorrection of Bohler's angle but
      urge avoidance of overcorrection and stress the importance of early surgical
      fixation after lateral skin wrinkling is found.

PMID- 11465129
TI  - Outcome of foot injuries in multiply injured patients.
AB  - In the past, foot injuries in patients with multiple trauma were thought to be of
      lesser importance than fractures of long bones. In one prospective study from the
      authors' institutions, however, multiple-trauma patients with foot injuries were
      shown to have a poorer functional outcome compared with matched controls. To
      address these concerns, this article has two parts. The first part is an overview
      of general principles in the treatment of foot injuries in polytrauma patients.
      The treatment of specific injuries is beyond the scope of this article, but an
      approach is highlighted that can be remembered when decisions are made regarding
      these severely injured patients. The second part reviews the findings from the
      authors' study, focusing on functional outcomes of multiple-trauma patients with
      foot injuries.

PMID- 11465130
TI  - Applications of ring fixators in complex foot and ankle trauma.
AB  - There is a growing base of literature that supports the use of external ring
      fixators in the treatment of complex foot and ankle fractures. Clinical studies
      that determine definitively the optimal treatment for particular injuries are
      absent. Small wire ring fixators have a growing role in allowing the
      stabilization of complex skeletal injuries with a minimum of iatrogenic soft
      tissue injury. Ring fixators should be considered in the algorithm of treatment
      of complex lower extremity fractures with associated significant soft tissue
      injury. One of the cornerstones of trauma management is the preservation of
      reconstructive options after injury. As interest in ankle arthroplasty increases
      and experience broadens, such options may be available to patients who sustain
      severe tibial plafond or talus fractures. It is imperative that hindfoot
      alignment and height be maintained and infection avoided so that reconstructive
      osteotomy, arthrodesis, and arthroplasty remain as options for patients who
      sustain severe trauma.

PMID- 11465131
TI  - Fractures of the tarsal bones.
AB  - Fractures involving the midtarsal bones are relatively uncommon. The morbidity
      associated with these injuries can be significant, however. Accurate diagnosis
      and appropriate treatment can help restore midfoot function and decrease the
      incidence of chronic pain. Treatment should preserve the function of the
      talonavicular joint, maintain the relative length of the medial and lateral
      columns, and protect the ligaments and soft tissues until adequate healing has
      occurred.

PMID- 11465132
TI  - Fractures of the calcaneus.
AB  - Fractures of the calcaneus (os calcis) are the most common of tarsal bone
      fractures, with an overall prevalence of approximately 2%. Despite increased
      experience with these types of fractures, however, there is considerable debate
      regarding their treatment and overall management. Controversies remain regarding
      the most appropriate classification system, treatment options, indications for
      surgery, surgical approaches, and post-operative management. This article
      presents a rational approach to the treatment of os calcis fractures based on
      current and past literature and the authors' preferred methods of treatment.

PMID- 11465133
TI  - Talar neck fractures.
AB  - Clinical management of talar neck fractures is complex and fraught with
      complications. As Gaius Julius Caesar stated: "The die is cast"; often the
      outcome of a talar neck fracture is determined at the time of injury. The authors
      believe, however, that better results can be achieved by following some simple
      guidelines. The authors advocate prompt and precise anatomic surgical reduction,
      preferring the medial approach with secondary anterolateral approach.
      Preservation of blood supply can be achieved by a thorough understanding of
      vascular pathways and efforts to stay within appropriate surgical intervals. The
      authors advocate bone grafting of medial neck comminution (if present) to prevent
      varus malalignment and rigid internal fixation to allow for joint mobilization
      postoperatively. These guidelines may seem simple, but when dealing with the
      complexity of talar neck fractures, the foot and ankle surgeon needs to focus and
      rely on easily grasped concepts to reduce poor outcomes.

PMID- 11465134
TI  - Talar body fractures.
AB  - Fractures to the body of the talus include a wide array of injuries, varying from
      relatively minor posterior tuberosity fractures to devastating comminuted body
      fractures. Fracture types include osteochondral fractures, sagittal transverse or
      coronal whole-body fractures, posterior tubercle fractures, lateral process
      fractures, and crush injuries. Treatment varies from excision of small fragments,
      such as arthroscopic treatment of osteochondral injuries, to open reduction and
      internal fixation of body fractures, usually by a medial malleolar osteotomy.
      Prognosis logically correlates with the magnitude of the injury with whole-body
      fractures, especially crush injuries, having the worst prognosis. Talar body
      fractures, similar to talar neck fractures, also can be complicated by subtalar
      arthritis, ankle arthritis, malunion, and avascular necrosis.

PMID- 11465135
TI  - Ankle fractures and syndesmosis injuries.
AB  - Ankle fractures are one of the most frequently treated injuries in orthopedic
      traumatology. The simple injuries often are forgiving and are managed easily and
      appropriately by closed treatment, but more complex injuries require recognition
      of possible associated injuries and anatomic internal fixation. Although
      adherence to general guidelines of fracture management usually suffices, some
      cases do not fall into a well-defined category, and clinicians are called on to
      use their experience and clinical knowledge to make treatment decisions that best
      ensure good clinical outcomes.

PMID- 11465136
TI  - The treatment of pilon fractures.
AB  - Soft tissue complications, skin slough, and superficial infection lead to deeper
      infection and amputation. By avoiding these complications, it is expected that
      better results can be obtained. Two techniques are available to do this. The
      first is to limit incisions and use external fixation to obtain stability. Even
      in these cases, care must be taken with the soft tissues. The second is a staged
      reconstruction, whereby stage one allows soft tissue stabilization. To this end,
      the fibula is plated, and transarticular external fixation is performed; this
      maintains anatomic length, preventing soft tissue contraction and permitting
      edema resolution. The second stage, formal tibial open reduction and internal
      fixation, is performed with plates and screws when operative intervention is
      safe. These methods appear to be equally effective in reducing major soft tissue
      complications. Surgeons should treat these complex fractures with the method with
      which they are most comfortable. Surgeons who feel comfortable with techniques of
      internal fixation are best qualified to perform open reductions. Surgeons who
      have experience with percutaneous fixation and hybrid external fixator
      application should use this method. Surgeons with limited or minimal experience
      with pilon fractures should consider fibula fixation and transarticular external
      fixation followed by transfer to an orthopedic trauma surgeon for definitive
      management.

PMID- 11465137
TI  - Staging of the neck in patients with oral cavity squamous cell carcinomas: a
      prospective comparison of PET, ultrasound, CT and MRI.
AB  - BACKGROUND: The choice of treatment in patients with oral malignancies depends on
      accurate pretreatment staging and particularly the detection of lymph node
      involvement. Therefore staging of the neck should be as accurate as possible.
      PATIENTS: One hundred and six patients with histologically proven squamous cell
      carcinoma of the oral cavity. STUDY DESIGN: In a prospective study, PET using
      fluoro-desoxy-glucose (18F-FDG), ultrasound, CT and MRI of head and neck were
      compared with the postoperative histologic tissue evaluation. Two thousand one
      hundred and ninety-six neck lymph nodes of 106 patients were investigated. In all
      patients the tumour was resected and a lymph node dissection was performed.
      RESULTS: The diagnostic procedures showed the following results when compared
      with the histological findings: PET: sensitivity 70%, specificity 82%, accuracy
      75%; Ultrasound: 84%, 68%, 76%; CT: 66%, 74%, 70%; MRI: 64%, 69% 66%. Thus PET
      showed the highest specificity while ultrasound had the highest sensitivity
      compared with the other staging procedures. A nonsignificant correlation was
      found between the size of a lymph node metastasis and the ability to detect it.
      In 10 patients, second primary tumours or distant metastases were detected by PET
      only. CONCLUSION: Due to the high number of small lymph node metastases from oral
      cavity carcinoma, the non-invasive neck staging methods are limited to a maximum
      accuracy of 76%. Elective neck treatment should be mandatory for all patients
      with squamous cell carcinoma of the oral cavity.

PMID- 11465138
TI  - Computer-aided 3-D 99mTc-DPD-SPECT reconstruction to assess mandibular invasion
      by intraoral squamous cell carcinoma: diagnostic improvement or not?
AB  - OBJECTIVE: A prospective study was designed to compare computer-aided 3-D 99mTc
      DPD-SPECT (Technetium-Dicarboxy propan-single photon emission CT) reconstruction
      with clinical examination, panoramic radiography, CT scan and conventional 99mTc
      DPD-SPECT investigation in the assessment of mandibular bone invasion by squamous
      cell carcinoma. PATIENTS AND METHODS: Between October 1997 and December 1999, 88
      patients with intraoral squamous cell carcinoma of the regions adjacent to the
      mandible were enrolled in this study. In 50 cases, mandibular resection
      (segmental or marginal) was performed based on the pre-treatment diagnostic
      results. Imaging studies were read independently by four experienced observers.
      RESULTS: No differences could be found between presurgical 3-D 99mTc-DPD-SPECT
      reconstruction and conventional 99mTc-DPD-SPECT investigation. Both techniques
      revealed a sensitivity of 100% whereas CT scan showed the greatest specificity
      (93.8%). SPECT investigation had a specificity of 91.6% and the greatest
      efficiency (95.4%). The greatest predictive positive value was found for CT scan
      (92.3%). Clinical examination and panoramic radiography displayed the lowest
      sensitivity, 82.5% vs. 85.0%, and specificity, 79.2% vs. 89.5% respectively.
      CONCLUSION: This investigation does not provide evidence that 3-D 99mTc-DPD-SPECT
      reconstruction has any advantages when compared to conventional 99mTc-DPD-ECT
      investigation in the assessment of mandibular invasion by squamous cell
      carcinoma. Despite a sensitivity of 100% the specificity is still in need of
      improvement. Until newer methods or techniques become available the combination
      of CT scanning and conventional 99mTc-DPD-SPECT investigation appears to be the
      best means of detecting tumour invasion preoperatively and is thus helpful in
      directing appropriate surgical procedure.

PMID- 11465139
TI  - Outcome of squamous cell carcinoma of the gingiva: a follow-up study of 83 cases.
AB  - BACKGROUND: Squamous cell carcinomas of the gingiva are relatively rare tumours.
      Standard treatment is based on surgery and radiotherapy. The extent of bone
      involvement affects mandibulectary indications. PURPOSE: A retrospective review
      of squamous cell carcinomas of the gingiva was performed to evaluate the
      incidence of mandibular or maxillary bone involvement. Indications for marginal
      and segmental bone resections are specified. MATERIAL: From 1985 to 1996, 83
      patients with squamous cell carcinoma of the gingiva were treated at the
      Department of Surgery (Institut Bergonie, Bordeaux, France) and at the Department
      of Maxillofacial and Plastic Surgery (Centre Hospitalier Universitaire, Bordeaux,
      France). Forty-three underwent surgery plus postoperative radiotherapy. Twenty
      two had flap reconstructions. Clinical evaluation and panorex roentgenography
      were the means used to evaluate bony invasion and to decide on the extent of bone
      resection. METHODS: A retrospective review of 83 consecutive patients was
      performed. This series is unusual in its homogeneity: surgery was performed by
      only two individuals and the radiotherapy was the responsibility of just two
      physicians. Outcome was calculated using the Kaplan-Meier method. RESULTS:
      Primary local control was achieved in 72 patients (87%). Overall survival and
      rate of recurrence were comparable to those of other squamous cell carcinomas of
      the oral cavity and oropharynx. CONCLUSION: Surgical resection continues to be
      the mainstay of treatment and this study tends to confirm the validity of
      modified neck dissection and marginal bone resection in suitably selected
      patients.

PMID- 11465140
TI  - Evaluating the neck for percutaneous dilatational tracheostomy.
AB  - PURPOSE: The aims of this article are to study how variations in the anatomy of
      the neck may influence the success of percutaneous dilatational tracheostomy
      (PDT). PATIENTS AND METHODS: Four hundred and ninety-seven patients were included
      in this study. Patients with a short neck and altered tracheal anatomy were
      evaluated on the basis of difficulty with PDT, use of long shank tracheostomy
      tubes, and need for open surgical tracheostomy. RESULTS: 33 (6.6%) patients had
      an apparently reduced cricoid ring to sternum distance and a deeply lying
      trachea. Nine of these patients were referred for open surgical tracheostomy. A
      further five patients had altered tracheal anatomy secondary to disease or
      surgery. Two of these patients were also referred for open surgical tracheostomy.
      Thus, unfavourable neck anatomy was responsible for 2.2% (11/497) of patients
      being referred for open surgical tracheostomy. CONCLUSION: Variations in the
      anatomy of the neck can make PDT both difficult and hazardous. Patients with a
      deeply lying trachea may need a long shank tube. Open surgical tracheostomy is
      indicated in some patients with a deeply lying trachea and conditions producing
      secondary deformity of the trachea. All patients should have a detailed history
      and thorough clinical examination of the neck and thorax prior to PDT. The
      selective use of chest radiography, MRI, and ultrasound assessment prior to PDT
      can assist in the identification of patients unsuitable for this technique.

PMID- 11465141
TI  - The submental route revisited using the laryngeal mask airway: a technical note.
AB  - The submental route for endotracheal intubation is well known and this paper
      reports the use of the same route for the laryngeal mask airway. This technique
      can be used whenever it is considered too awkward to perform submental, transoral
      or transnasal endotracheal intubations. When the surgery has been completed, the
      mouth is left open to allow the laryngeal mask to be removed; it cannot be left
      in place in cases of intermaxillary fixation. It is necessary to detach the
      laryngeal mask orally, never submentally, as it is impossible to remove the mask
      via the submental route.

PMID- 11465142
TI  - Histological changes in the rabbit condyle following posterolateral disk
      perforation.
AB  - PURPOSE: To examine changes in condylar cartilage following perforation in the
      posterolateral region of the articular disk of the craniomandibular joint of a
      rabbit. MATERIAL AND METHODS: The circular perforation in the left joint of 25
      female Japanese white rabbits measured precisely one-sixteenth of a disk.
      Histological examination, including the immunohistochemical proliferating cell
      nuclear antigen (PCNA) procedure, was performed on separate sets of five rabbits
      each 2, 4, 8, 12, and 24 weeks postoperatively. RESULTS: Microscopic examination
      revealed hypertrophy of the condylar cartilage with osteophyte formation up to 8
      weeks after perforation. Proliferative activity then decreased near the condylar
      surface as the perforation flattened. Twenty-four weeks postoperatively, the
      condylar surface was found to be fibrous and flattened. Positive PCNA results in
      cartilage cells indicated proliferation following disk perforation which peaked
      in the 4th week and then decreased. CONCLUSION: Disk perforation was followed
      initially by hypertrophy of condylar cartilage, and later by degeneration of the
      condylar surface. Although osteoarthritic cartilage was found 24 weeks after
      perforation, degeneration decreased over time. This suggests that remodelling
      took place after the perforation.

PMID- 11465143
TI  - Sonography of the temporomandibular joint from 60 examinations and comparison
      with MRI and axiography.
AB  - BACKGROUND AND OBJECTIVE: Establishing a diagnosis of temporomandibular joint
      disorder is mainly based on clinical assessment, functional examination, nuclear
      magnetic resonance imaging (MRI) and axiography. Sonographic examination was
      compared with MRI and axiography in assessing temporomandibular joint (TMJ)
      function in 55 patients. PATIENTS AND METHODS: Fifty-five patients with different
      TMJ problems were examined clinically, by means of axiography, sonography and
      some also by MRI. The range of motion was measured by sonography and axiography
      and the results compared using Student's t-test. Anatomical details diagnostic
      for disc-displacement were tested by sonography and MRI. RESULTS: The average
      time required for sonography was 2 min and for axiography 20 min. The mean
      measurement differences for condylar movement in maximal mouth opening was 1.7
      mm, for protrusion 1.6 mm and for mediotrusion 2.5 mm. The range of condylar
      movement as measured by sonography and axiography coincided for opening and for
      protrusion (statistically significant). No significance was found for lateral
      excursions. The concordance in diagnosis of disc dislocation, hypermobility and
      impaired range of motion when comparing ultrasound with MRI was 83%. All
      sonographic examinations were performed by one person only. Sixty repeat
      examinations in patients produced no complaints and showed an absolute range of
      difference of 0.6 mm, with a relative range of 7%. Student's t-test was
      significant (p<0.05) (two repetitive measurements). CONCLUSION: Sonography proved
      to be a fast and reliable method for evaluating the range of movement of the TMJ.
      The lateral joint capsule, lateral disc, and upper condyle could be demonstrated.
      Pathological processes such as anterior or lateral disc displacement, disc
      perforation, seroma following contusion, capsular fibrosis, crystalline
      structures in the synovia and fracture dislocation of the condyle could be
      diagnosed with considerable reliability when compared with MRI. However, the
      medial aspect of the joint, medial disc dislocation and the angulation of the
      condylar slope could not be seen.

PMID- 11465144
TI  - Temporomandibular joint morphology and disc position in skeletal class III
      patients.
AB  - INTRODUCTION: The purpose of this study was to investigate the relationship
      between temporomandibular joint (TMJ) morphology, including discal tissue and
      clinical symptoms in class III dentofacial deformity patients. MATERIAL AND
      METHODS: Forty-four patients were examined with lateral, frontal and axial
      cephalograms. They were divided into two groups, consisting of a class III
      symmetry and a class III asymmetry group. By using magnetic resonance imaging the
      88 joints could be classified into four types on the basis of disc position and
      shape: anteriorly displaced disc, anterior type, fully-covered type and posterior
      type. Furthermore, TMJ morphology was measured tomographically in the sagittal
      plane. RESULTS: Anteriorly displaced discs in the asymmetry group (56.8%)
      occurred significantly more frequently than in the symmetry group (18.2%; p
      <0.05). TMJ symptoms (clicking, crepitus, closed lock, pain) were seen in 17/44
      joints (38.6%) of the symmetry and 24/44 joints (54.5%) of the asymmetry group,
      for a total of 41/88 joints (46.6%). There were no differences in joint space
      ratio and condyle ratio. However, the fossa ratio on the deviation side was
      significantly higher than on the nondeviation side in the asymmetry group
      (p<0.05). CONCLUSION: The incidence of internal derangement in asymmetrical class
      III patients is higher than in symmetrical mandibular prognathism, and this
      difference is associated with a difference in TMJ morphology of both sides.

PMID- 11465145
TI  - Release of extra-articular ankylosis by coronoidectomy and insertion of a free
      abdominal flap: case report.
AB  - INTRODUCTION: It is generally agreed that an effective treatment for extra
      articular ankylosis may be coronoidectomy and excision of scar tissue. But these
      conventional procedures have shown a high rate of recurrence of ankylosis due to
      heterotopic bone and fibrous tissue formation. OBJECTIVE AND PATIENT: We report a
      case in whom a coronoid osteotomy and insertion of a free abdominal flap was used
      to treat ankylosis of the mandible following radiotherapy for maxillary cancer.
      RESULTS: This procedure prevented recurrence of ankylosis by heterotopic bone and
      fibrous tissue formation. In addition, this flap reduced the risk of
      postoperative infection and promoted primary healing. CONCLUSION: The procedure,
      coronoidectomy and insertion of a free flap, was successful because the well
      vascularized musculocutaneous flap occupied the dead space, and replaced the
      shortage of oral mucosa consequently inhibiting the recurrence of extra-articular
      ankylosis.

PMID- 11465146
TI  - Psychological study of cleft palate children with or without cleft lip by kinetic
      family drawing.
AB  - To clarify how cleft palate children with or without cleft lip perceive their
      family, we applied the Kinetic Family Drawing (KFD) technique to 60 cleft palate
      children (with or without cleft lip). The children were aged 7-9 years (in the 1
      3 grade of elementary school) and attended the Department of Oral Surgery, Nagoya
      University Hospital, between 1990 and 1997. Controls consisted of 100 normal
      elementary school children of the same age. Major findings were: (1) Compared
      with normal children, cleft lip and palate boys and cleft palate only girls drew
      their self-images significantly more often in region D (lower right) and in
      region A (upper left), respectively. (2) Cleft palate children with or without
      cleft lip felt anxiety and fear toward their family, rarely viewing their homes
      as a restful place; this suggested insecurity. Uniquely dynamic relations were
      also suggested in their homes. (3) Cleft palate children with or without cleft
      lip often perceived their father or mother as persons easily acceptable in
      society. Rather remote psychological distance between parents and cleft palate
      children with or without cleft lip was suggested.

PMID- 11465147
TI  - The quadrangular osteotomy revisited.

PMID- 11465148
TI  - Multiple oxidants in cytochrome P450 catalyzed reactions: implications for drug
      metabolism.
AB  - The activation of molecular oxygen by Cytochromes P450 to the ultimate mono
      oxygen oxidant species involves three distinct dioxygen species coordinated to
      the heme iron. These intermediates have different chemical properties, and have
      recently been proposed to participate in some Cytochrome P450-catalyzed oxidation
      reactions. This article reviews the extent of our current knowledge on the roles
      proposed for the heme- peroxo, hydroperoxo, and superoxo complexes in various
      reactions. The extent to which such species contribute to the breadth of
      reactions catalyzed by Cytochrome P450 has yet to be defined, and more definitive
      experiments are needed to establish such species in the reactions they are
      proposed to effect.

PMID- 11465149
TI  - Enzyme kinetics of cytochrome P450-mediated reactions.
AB  - The most common drug-drug interactions may be understood in terms of alterations
      of metabolism, associated primarily with changes in the activity of cytochrome
      P450 (CYP) enzymes. Kinetic parameters such as Km, Vmax, Ki and Ka, which
      describe metabolism-based drug interactions, are usually determined by
      appropriate kinetic models and may be used to predict the pharmacokinetic
      consequences of exposure to one or multiple drugs. According to classic Michaelis
      Menten (M-M) kinetics, one binding site models can be employed to simply
      interpret inhibition (pure competitive, non-competitive and uncompetitive) or
      activation of the enzyme. However, some cytochromes P450, in particular CYP3A4,
      exhibit unusual kinetic characteristics. In this instance, the changes in
      apparent kinetic constants in the presence of inhibitor or activator or second
      substrate do not obey the rules of M-M kinetics, and the resulting kinetics are
      not straightforward and hamper mechanistic interpretation of the interaction in
      question. These unusual kinetics include substrate activation (autoactivation),
      substrate inhibition, partial inhibition, activation, differential kinetics and
      others. To address this problem, several kinetic models can be proposed, based
      upon the assumption that multiple substrate binding sites exist at the active
      site of a particular P450, and the resulting kinetic constants are, therefore,
      solved to adequately describe the observed interaction between multiple drugs.
      The following is an overview of some cytochrome P450-mediated classic and
      atypical enzyme kinetics, and the associated kinetic models. Applications of
      these kinetic models can provide some new insights into the mechanism of P450
      mediated drug-drug interactions.

PMID- 11465150
TI  - Pharmacology of chiral compounds: 2-arylpropionic acid derivatives.
AB  - Molecules exist as three dimensional structures. Therefore they can exist in
      symmetrical and asymmetrical forms. Molecules with an asymmetric centre are
      chiral. If the molecule and its mirror image are non-superimposable, the
      relationship between the two molecules is enantiomeric and the two stereoisomers
      are enantiomers. Since enantiomers have very similar or identical physicochemical
      properties, it is very difficult to distinguish between them in an achiral
      environment. However, once in a chiral environment, as in the body, they exhibit
      clear differences. In fact, most of the physiological processes in nature are
      stereospecific. Stereospecificity can occur in pharmacokinetic processes, in
      particular that utilise a carrier protein, receptor or enzyme. In addition,
      stereoselectivity occurs in pharmacodynamic processes and the differences between
      enantiomers can be either qualitative and quantitative. 2-arylpropionic acid
      derivatives (2APAs - profens) are an important subgroup within the class of
      NSAIDs. These are chiral compounds marketed as racemic mixtures. Some members of
      the group in an species-dependent manner undergo a special type of metabolic
      transformation leading to partial inversion to the optical antipode through a
      specific conjugation with CoA (coenzyme A) and subsequent epimerization. This
      metabolic inversion has not only pharmacological consequences (related to
      clinical effect) but also toxicological consequences such as, formation of hybrid
      triglycerides and even inhibition of fatty acid beta-oxidation. Differences on
      inversion rate between compounds and species will be discussed as well as its
      modification by different patho-physiologic processes such as, inflammation.

PMID- 11465151
TI  - Pharmacodynamics of high-dose chemotherapy.
AB  - There is usually considerable variability in anticancer drug plasma levels when
      delivered at high doses requiringstem-cell support. Given their narrow
      therapeuticwindows and wide interpatient pharmacokinetic variability, drug
      monitoring and pharmacokinetic-directed dosing representan attractive strategy in
      this setting. A major previous requirement to successful application of
      therapeuticdrug monitoringis identificationof a significant and clinically
      meaningful pharmacodynamic correlation between a pharmacokinetic parameter and a
      toxic or therapeutic outcome, or preferably, both. In this review, we will
      analyze the current knowledge of identified pharmacodynamic correlations in high
      dose chemotherapy. We will summarize the observations from other authors and our
      own, on drugs employed at high doses, such as cyclophosphamide, melphalan,
      busulfan, carmustine, paclitaxel, or docetaxel.

PMID- 11465152
TI  - Bestatin as an experimental tool in mammals.
AB  - Bestatin, an antibiotic of microbial origin, is a potent inhibitor of some, but
      not all aminopeptidases. It can be administered, with low toxicity, to cultured
      cells, intact animals and humans. It has become a useful tool in elucidating the
      physiological role of some mammalian exopeptidases in the regulation of the
      immune system, in the growth of tumors and their invasion of surrounding tissues,
      and in the degradation of cellular proteins. Bestatin-sensitive enzymes play
      important roles in the digestion and absorption of peptides in the brush border
      of the intestine and the kidney, in the reproductive system, and in the
      metabolism of opioid peptides and leukotrienes. Aminopeptidase N emerges as the
      major target for the effects of bestatin on the immune system and some of its
      effects on tumor growth and the endometrium. It is also the major bestatin
      sensitive enzyme involved in the degradation of oligopeptides on the surface of
      intestine and kidney brush borders, and the inactivation of enkephalins in the
      brain. Bestatin-sensitive cytosolic exopeptidases are important in the
      degradation to amino acids of di- and tripeptides generated in most cells by
      cellular protein degradation, as well as those absorbed through the brush border
      of intestine and kidney. Inhibition of one of these exopeptidases, cytosol
      alanine aminopeptidase, results in apoptosis. Bestatin-sensitive cystinyl
      aminopeptidase is abundant in placenta. Two bestatin-sensitive enzymes,
      aminopeptidase B and nardilysin, are particularly abundant in late spermatids.
      Finally bestatin-sensitive LTA4 hydrolase generates the potent chemotactic agent,
      LTB4.

PMID- 11465153
TI  - Reporting on violence: bringing a public health perspective into the newsroom.
AB  - The authors present a case study of a collaboration among the Berkeley Media
      Studies Group, the University of Missouri-Columbia School of Journalism, and
      journalist Jane Ellen Stevens to introduce to five metropolitan newspapers new
      violence-reporting techniques that include a public health perspective. A
      handbook was designed for journalists, and workshops were conducted to explore
      with editors and reporters how newspapers can report highly unusual crimes and
      yet avoid misrepresenting the patterns of violence in their communities and
      creating misguided fear in the public. This case study documents how journalists
      can be meaningfully engaged on this topic with people from public health despite
      typical barriers to access faced by public health practitioners and solid
      resistance from many editors and reporters. The authors describe goals,
      objectives, and activities across five daily newspapers along with journalists'
      reactions, concerns, and resistance to the issues that were raised.

PMID- 11465154
TI  - Reporting on violence: bringing the newsroom into health education research.

PMID- 11465155
TI  - Managing healthy eating: definitions, classifications, and strategies.
AB  - This study sought to enhance understanding of how people conceptualize and manage
      healthy eating. An interpretivist approach employed the constant comparative
      method to analyze 79 open-ended interviews with individuals about food choices
      and eating behaviors for health-related themes. Participant reports depicted
      cognitive systems for defining healthy eating, where personal meanings evolved
      through ongoing exposure to a variety of experiential and informational sources.
      Participants' definitions of healthy eating clustered around seven themes
      forrelating food and eating to their personal health. Healthy eating definitions
      shaped how participants categorized food and eating situations as healthy and
      unhealthy. Participants described healthy eating strategies that were
      differentially associated with various healthy eating themes. These findings
      provide an emic perspective of how a diverse sample of adults conceptualize and
      manage healthy eating. Exposing the implicit and multiplistic nature of healthy
      eating conceptions provides information useful to health educators promoting
      behavior changes.

PMID- 11465156
TI  - Correlates of participation in a family-directed tobacco and alcohol prevention
      program for adolescents.
AB  - This study examined correlates of program initiation and completion in a family
      directed program that involved families of adolescents throughout the United
      States. Correlates varied by whether program initiation, program completion, or
      the number of activities completed was the indicator of participation. In final
      regression models, participation was relatively likely by non-Hispanic whites
      when compared with persons of race/ethnicity other than white, black, and
      Hispanic; by families with a female adolescent as the program recipient; by
      families with mothers who had many years of education; and by families with both
      parents living in the household. There was more participation if parents thought
      their child would smoke in the future and if the parent thought the adolescent
      did not smoke currently. Participation was higher if the adolescent felt strongly
      attached to the parent and if parents did not smoke. The findings are considered
      in the context of similar programs and future research on family-directed
      programs to prevent adolescent tobacco and alcohol use.

PMID- 11465157
TI  - Disentangling measures of individual perceptions of community social dynamics:
      results of a community survey.
AB  - This study examined how different measures of individual perceptions of community
      social dynamics relate to each other and how these measures relate to self
      reported general health and depressive symptoms. Results of a principal
      components analysis conducted to investigate the interrelationships between these
      individual measures suggest that these measures measure separate phenomena. In
      addition, in results of multiple-regression analyses conducted to examine
      associations between the various measures of individual perceptions of community
      social dynamics and the dependent variables of self-reported general health and
      depressive symptoms, sense of community, perceived neighborhood control, and
      neighborhood participation were all associated with the outcome variables in
      separate regression models. In a regression model with these three variables
      added to control variables, only sense of community was significantly, albeit
      modestly, associated with depressive symptoms and self-reported general health.

PMID- 11465158
TI  - A critical examination of community-based responses to household food insecurity
      in Canada.
AB  - Over the past two decades, household food insecurity has emerged as a significant
      social problem and serious public health concern in the "First World." In Canada,
      communities initially responded by establishing ad hoc charitable food assistance
      programs, but the programs have become institutionalized. In the quest for more
      appropriate and effective responses, a variety of community development programs
      have recently been initiated. Some are designed to foster personal empowerment
      through self-help and mutual support; others promote community-level strategies
      to strengthen local control over food production. The capacity of current
      initiatives to improve household food security appears limited by their inability
      to overcome or alter the poverty that under-pins this problem. This may relate to
      the continued focus on food-based responses, the ad hoc and community-based
      nature of the initiatives, and their origins in publicly funded health and social
      service sectors.

PMID- 11465159
TI  - Can children teach their parents about asthma?
AB  - The Open Airways for Schools (OAS) program has been shown to improve the self
      management skills and health outcomes of students with asthma in Grades 3 to 5.
      This report examines the impact of OAS on students' parents. Because pilot
      studies showed that parental attendance at school-based sessions was low, the
      authors held six sessions at school for children and gave children homework
      assignments to complete with parents at home to teach parents about asthma and
      build support for children's self-management efforts. Analysis of 1-year follow
      up data showed that children's participation in OAS was a significant predictor
      of parental self-management skills (p <.03) and that OAS children's communication
      was more strongly associated than controls' with parents' self-management (p =
      .05). The findings show that health education activities brought home from school
      by children can positively influence parents' self-management of a complex
      chronic disease such as asthma.

PMID- 11465160
TI  - STS database activities and you: "What's in it for me?".

PMID- 11465161
TI  - Steroid-free maintenance immunosuppression after heart transplantation.
AB  - BACKGROUND: Steroids are routinely used in almost all immunosuppressive protocols
      after cardiac transplantation. The metabolic side effects of steroids are well
      known and could lead to significant morbidity and mortality in the posttransplant
      period. There is growing evidence to suggest that steroids may not be a
      requirement for adequate immunosuppression and that morbidity may be reduced by
      withdrawing steroids in select patients. We have reviewed our series of patients
      undergoing heart transplantation in whom steroids were weaned postoperatively.
      METHODS: We retrospectively reviewed all adult patients undergoing heart
      transplantation at our institution between November 1993 and April 2000 treated
      with a-triple-drug immunosuppressive regimen. Medications were recorded at
      discharge and at 6, 12, and 24 months posttransplant to determine the success of
      steroid weaning. Freedom from infection and rejection as well as overall survival
      was calculated using Kaplan-Meier methods. RESULTS: By 24 months posttransplant,
      almost 70% of patients were receiving double-drug therapy. Survival for the
      entire group was excellent with 1-, 3-, and 5-year survival of 98%+/-2.0%,
      93.2%+/-3.8%, and 88.3%+/-6.0%, respectively. Freedom from rejection at 6 months
      was 60.7%+/-6.5%, at 1 year was 60.7%+/-6.5%, and at 2 years was 58.5%+/-6.7%.
      Infectious complications were low with freedom from infection at 6 months of
      78.5+/-5.5%, at 1 year of 76.5%+/-5.7%, and at 2 years of 72.0%+/-6.2%.
      CONCLUSIONS: Our data suggest that an immunosuppressive regimen without long-term
      steroid administration results in excellent survival rates without an apparent
      increase in rejection or infectious complications.

PMID- 11465162
TI  - Backtable heat-enhanced preconditioning: a simple and effective means of
      improving function of heart transplants.
AB  - BACKGROUND: Cardiac harvest teams are usually committed to immediately transfer
      the explanted donor heart into its cold storage solution. We tested the opposite
      hypothesis that a brief prestorage episode of heat-enhanced ischemic
      preconditioning could be protective. METHODS: Fifty-three isolated isovolumic rat
      hearts underwent 4 hours of cold (4 degrees C) storage in the Celsior
      preservation solution and 2 hours of reperfusion. Control hearts were immediately
      immersed after arrest. In the 3 treated groups, 2 customized thermal probes were
      first applied onto the left ventricular free wall of the explanted heart at 22
      degrees C, 37 degrees C or 42.5 degrees C for 15 minutes before immersion. Each
      of the selected temperatures were monitored at the probe-tissue interface by a
      thermocouple. RESULTS: Whereas base line end-diastolic pressure was set at = 8 mm
      Hg in all groups, it increased during reperfusion (mean +/- SEM) to 28+/-3, 27+/
      3, 17+/-1, and 18+/-2 mm Hg in control, 22 degrees C, 37 degrees C and 42.5
      degrees C-heated hearts, respectively (37 degrees C and 42.5 degrees C: p < 0.05
      versus controls and 22 degrees C). Slopes of pressure-volume curves featured
      similar patterns. Likewise, reperfusion dP/dT (mm Hg/s(-1)) was significantly
      lower in control and 22 degrees C hearts (1,119+/-114 and 1,076+/-125,
      respectively) than in those undergoing prestorage heating to 37 degrees C and
      42.5 degrees C (1,545+/-109 and 1,719+/-111, p < 0.05 and p < 0.01 versus
      controls and 22 degrees C, respectively). Western blot analysis of LV samples did
      not demonstrate any upregulation of HSP 72 in either group. Conversely, the
      involvement of preconditioning was evidenced by the loss of protection in the
      42.5 degrees C-heated hearts when, in 2 additional groups, the storage solution
      was supplemented with either the protein kinase C and tyrosine kinase inhibitors
      chelerythrine (5 micromol/L) and genistein (50 micromol/L) or the mitochondrial
      K(ATP) channel inhibitor 5-hydroxydecanoate (200 micromol/L). CONCLUSIONS: A
      brief period of postexplant ischemia with enhancement by topical heating
      ("backtable preconditioning") could be a simple and effective means of improving
      the functional recovery of heart transplants.

PMID- 11465163
TI  - Off-pump coronary artery bypass is associated with improved risk-adjusted
      outcomes.
AB  - BACKGROUND: The impact of off-pump median sternotomy coronary artery bypass
      grafting procedures on risk-adjusted mortality and morbidity was evaluated versus
      on-pump procedures. METHODS: Using the Department of Veterans Affairs Continuous
      Improvement in Cardiac Surgery Program records from October 1997 through March
      1999, nine centers were designated as having experience (with at least 8%
      coronary artery bypass grafting procedures performed off-pump). Using all other
      34 Veterans Affairs cardiac surgery programs, baseline logistic regression models
      were built to predict risk of 30-day operative mortality and morbidity. These
      models were then used to predict outcomes for patients at the nine study centers.
      A final model evaluated the impact of the off-pump approach within these nine
      centers adjusting for preoperative risk. RESULTS: Patients treated off-pump (n =
      680) versus on-pump (n = 1,733) had lower complication rates (8.8% versus 14.0%)
      and lower mortality (2.7% versus 4.0%). Risk-adjusted morbidity and mortality
      were also improved for these patients (0.52 and 0.56 multivariable odds ratios
      for off-pump versus on-pump, respectively, p < 0.05). CONCLUSIONS: An off-pump
      approach for coronary artery bypass grafting procedures is associated with lower
      risk-adjusted morbidity and mortality.

PMID- 11465164
TI  - Coronary artery bypass grafting using the radial artery: midterm results in a
      Japanese institute.
AB  - BACKGROUND: To avoid remote cardiac events associated with graft occlusions,
      arterial conduits are being increasingly utilized in coronary artery bypass
      grafting (CABG). The development of antispasmic agents has enabled the use of the
      radial artery as a graft conduit in CABG. METHODS: Between December 1995 and
      December 1998, 920 consecutive isolated CABG operations were performed at Shin
      Tokyo Hospital. The radial artery was used for graft conduits in 475 of these
      patients, and their data were analyzed in this study. The patients were followed
      to determine midterm graft patency, cardiac events, and survival. All data are
      given as mean +/- standard deviation. The end points were patient death or
      occurrence of cardiac events. RESULTS: The radial artery was used in 475 patients
      (366 males and 109 females, with a mean age of 64.5+/-8.5 years). The left
      internal mammary artery was used in 94.9% of patients, the right internal mammary
      artery in 17.5%, the gastroepiploic artery in 50.9%, the inferior epigastric
      artery in 0.2%, and the saphenous vein in 39.2%. The in-hospital morbidity and
      mortality rates of the studied group were 12.8% and 0.6%, respectively. A major
      complication related to radial artery harvesting, compartment syndrome of the arm
      due to postoperative bleeding, was observed in 1 patient. No postoperative
      myocardial infarction attributable to radial artery bypass was observed. During
      the late follow-up period of 3.5+/-0.9 years, cardiac events were observed in 63
      patients, giving actuarial 2- and 3-year event-free rates of 92.8% and 89.6%,
      respectively. A total of 24 late deaths were noted, including seven cardiac
      deaths, giving actuarial 2- and 3-year survival rates of 98.1% and 97.2%,
      respectively. Postoperative angiography was performed in selected patients. The
      cumulative graft patency rate of the radial artery was 93.0% during the mean
      angiographical follow-up period of 1.5+/-1.1 years. CONCLUSIONS: No adverse
      effects were noted after CABG using a radial artery graft in this short- and
      midterm follow-up period.

PMID- 11465165
TI  - Arm complications after radial artery procurement for coronary bypass operation.
AB  - BACKGROUND: Radial arteries are being used frequently for coronary artery bypass
      conduits, and surgeons are appropriately concerned about the risks of ischemia,
      infection, and neurologic dysfunction of the "donor" arm. We present our record
      of donor site complications, with emphasis on the safety of radial usage in
      patients older than 65 years of age. METHODS: A total of 343 radial arteries were
      removed from 217 patients, aged 37 to 83 years. Forty-nine (23%) of the patients
      were women; 126 of the radial arteries were from patients aged 65 years or older.
      Four patients died. In the remaining 213 patients, 338 donor arms were examined
      for at least 6 weeks postoperatively for evidence of infection, ischemia,
      hematoma, seroma, or paresthesia. RESULTS: No donor arms developed symptoms of
      'ischemia or motor dysfunction. Two of 338 (0.6%) arms developed hematomas
      requiring operative drainage. Relatively minor complications of stitch abscesses,
      skin dehiscence, superficial infection, and small hematomas or seromas affected
      another 14 arms (4.1%). Cutaneous paresthesias in the radial distribution of the
      lateral antebrachial cutaneous nerve or superficial branch of the radial nerve
      were noted postoperatively in 36 arms (10.7%). The risk of any arm complication
      occurring was 13% in the 65 and older group and 17% in those less than 65 years
      old (p = NS). CONCLUSIONS: The risk of a major arm complication from radial
      artery harvesting for coronary bypass is low, even in patients of advanced age.

PMID- 11465166
TI  - Nitric oxide system in needle-induced transmyocardial revascularization.
AB  - BACKGROUND: Nitric oxide (NO) promotes endothelial proliferation and migration,
      essential for angiogenesis. The purpose of this study was to determine the
      cellular expression of inducible and endothelial nitric oxide synthases (iNOS and
      eNOS) in an ischemic cardiomyopathy animal model of needle-induced
      transmyocardial revascularization (TMR). METHODS: Myocardial infarction was
      created in rats by ligating the left coronary artery, and animals were divided
      into two groups: no-TMR group (served as control) and TMR group (underwent
      concomitant TMR by the creation of six transmural channels with a 25-gauge needle
      in the ischemic area). Rats were sacrificed at intervals of 1, 2, 4, and 8 weeks.
      Immunohistochemistry using specific antisera was performed for iNOS, eNOS, and
      endothelial cell marker factor VIII. Vascular density and positive staining area
      with either iNOS or eNOS were assessed in the infarcted myocardium. RESULTS:
      Vascular density in the infarcted myocardium was significantly increased in the
      TMR group (p < 0.001). The positive staining area for iNOS and the intensity of
      iNOS immunoreactivity in cardiomyocytes, vascular endothelium, and macrophages
      were significantly greater in the TMR group (p < 0.05). However, these
      differences were seen only in the first 2 weeks after TMR. There was no
      significant difference in the expression of eNOS between groups. CONCLUSIONS: A
      mechanical injury using needle puncture in an ischemic myocardium increased
      vascular density and is associated with increased expression of myocardial iNOS.
      Increased production of NO derived from iNOS may contribute to the angiogenic
      response of TMR.

PMID- 11465167
TI  - Pulmonary thromboendarterectomy combined with other cardiac operations:
      indications, surgical approach, and outcome.
AB  - BACKGROUND: Patients with pulmonary hypertension due to chronic thromboembolic
      disease benefit from pulmonary thromboendarterectomy. A subset of these patients
      present with concomitant coronary or valvular disease. METHODS: From July 1990 to
      July 2000, 90 patients (68 males, 22 females, mean age 68 years) with pulmonary
      vascular resistance (PVR) ranging from 297 to 2261 dynes x sec x cm(-5) underwent
      pulmonary thromboendarterectomy in conjunction with coronary bypass grafting (59
      patients), coronary artery bypass grafting/foramen ovale closure (24 patients),
      tricuspid annuloplasty (3 patients), mitral valve repair (2 patients), and aortic
      valve replacement (2 patients). The perioperative and hemodynamic outcomes of
      these patients were compared with the cohort of 1,100 isolated pulmonary
      thromboendarterectomies performed at our institution during this time. RESULTS:
      Overall perioperative survival (93.3%; 84 of 90 patients) and mean diminution in
      PVR (521 dynes x sec x cm(-5)) for patients undergoing combined operations were
      similar to those undergoing pulmonary thromboendarterectomy alone (94.2%
      survival; 1034 of 1100 patients; 547 dynes x sec x cm(-5) mean PVR reduction).
      Although patients undergoing combined operations were older (mean age 68 vs 50
      years, p < 0.0001), had longer hospital stays (median 14 vs 9 days), and had
      worse left ventricular function (mean preoperative cardiac output 3.1 vs 4.4, p <
      0.0001), there was no difference in cross-clamp time, resolution of tricuspid
      regurgitation, or postoperative systolic function between these two groups.
      CONCLUSIONS: Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary
      hypertension may be performed safely in conjunction with other cardiac
      operations. Older patients evaluated for pulmonary thromboendarterectomy should
      be screened for concomitant coronary and valvular disease.

PMID- 11465168
TI  - Magnetic resonance imaging findings and postoperative neurologic dysfunction in
      elderly patients undergoing coronary artery bypass grafting.
AB  - BACKGROUND: Small cerebral infarctions are common in elderly patients, but the
      association between the magnetic resonance imaging finding and neurologic
      dysfunction after coronary artery bypass grafting has not been evaluated.
      METHODS: We determined, prospectively, whether varying degrees of abnormal
      findings on magnetic resonance images of the brain increased the incidence of
      preoperative cognitive decline, postoperative neuropsychological dysfunction, and
      stroke in 421 elderly patients (> or = 60 years) undergoing coronary artery
      bypass grafting. RESULTS: Control patients (almost normal or leukoaraiosis, n =
      212) had rates of postoperative neuropsychological dysfunction (7%) and stroke
      (1.4%); the small infarctions group (some small infarctions, n = 126) had rates
      of 13% and 5.6%, respectively; whereas patients with multiple infarctions
      (multiple small infarctions or broad infarctions, n = 83) had rates of 20% and
      8.4%, respectively (p = 0.004, p = 0.013). In the group with multiple
      infarctions, 49 patients (59%) were asymptomatic and 21 patients (25%) had
      cognitive decline. Stepwise logistic regression analysis demonstrated that the
      significant predictors of multiple small infarctions or large infarctions were
      history of cerebrovascular disease, renal insufficiency, cognitive decline, and
      cerebral arteriosclerosis. CONCLUSIONS: Multiple infarctions significantly
      increase the risk of neurologic dysfunction after coronary artery bypass
      grafting. Routine screening for preoperative cognitive decline should be
      performed to detect underlying ischemic cerebral disease in elderly patients.

PMID- 11465169
TI  - Pneumonia after cardiac surgery is predictable by tracheal aspirates but cannot
      be prevented by prolonged antibiotic prophylaxis.
AB  - BACKGROUND: The purpose of this study was to assess the value of tracheal
      aspirate as a predictor of pneumonia after coronary artery bypass grafting and to
      evaluate the efficacy of prolonged perioperative antibiotic prophylaxis. METHODS:
      Tracheal aspirates of 500 patients undergoing coronary artery bypass grafting
      were taken immediately after intubation and analyzed for microorganisms by Gram
      stain and semiquantitative microbiologic cultures. All patients received 2 g
      ceftriaxone as a single-dose perioperative antibiotic prophylaxis before
      operation. Results of Gram stains were available before the patients were
      transferred to the intensive care unit. After the results were known, both groups
      of patients (positive Gram stain, group 1; negative Gram stain, group 2) were
      randomly assigned to either conventional antibiotic prophylaxis (A), consisting
      of ceftriaxone 2 g on postoperative day 1, or prolonged antibiotic prophylaxis
      (B), with ticarcillin + clavulanic acid 3 x 5.2 g during 72 hours. RESULTS: From
      500 patients, 91 had a positive Gram stain whereas 409 had a negative one. The
      incidence of pneumonia was significantly higher in patients with preoperative
      positive tracheal aspirates (15.3%) than in patients with a negative one (3.6%; p
      < 0.01). However, prolonged prophylaxis did not reduce the rate of postoperative
      pneumonia, which was as high as 13% in untreated positive patients versus 17% in
      treated positive patients, and 2% in untreated negative patients versus 4% in
      treated patients. In patients who had pneumonia, there was a high correlation
      between the microorganisms found in preoperative aspirates and those observed
      when aspirates were repeated (100% correlation in patients with conventional
      antibiotic prophylaxis and 87% in those with prolonged prophylaxis). CONCLUSIONS:
      Early postoperative pneumonia (<7 days) is most likely caused by microorganisms
      that colonize the respiratory tract before operation. The risk of pulmonary
      infection after coronary artery bypass grafting can be predicted from the
      preoperative tracheal aspirates. Prolonged perioperative antibiotic prophylaxis
      has no efficacy in reducing the incidence of pulmonary infections.

PMID- 11465170
TI  - Inducible nitric oxide production is an adaptation to cardiopulmonary bypass
      induced inflammatory response.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) increases nitric oxide (NO) production
      by the activation of NO synthases (NOS). However, the role of NO from inducible
      NOS (iNOS) in CPB-induced inflammatory response remains unclear. We examined the
      effect of a selective iNOS inhibitor, aminoguanidine, on CPB-induced inflammatory
      response in a rat-CPB model. METHODS: Adult Sprague-Dawley rats underwent 60
      minutes of CPB (100 mL x kg(-1) x min(-1), 34 degrees C). Group A (n = 10)
      received 100 mg/kg of aminoguanidine intraperitoneally 30 minutes before the
      initiation of CPB, and group B (n = 10) served as controls. RESULTS: There were
      significant time-dependent changes in plasma interleukin (IL)-6, IL-8, nitrate +
      nitrite, the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr, an
      indicator of peroxynitrite formation), and respiratory index (RI). Three hours
      after CPB termination, IL-6, IL-8, and RI were significantly higher in group A
      (IL-6, 397.5+/-80.6 pg/mL; IL-8, 26.99+/-6.57 ng/mL; RI, 1.87+/-0.31) than in
      group B (IL-6, 316.5+/-73.9 pg/mL, p <0.05; IL-8, 17.21+/-3.12 ng/mL, p < 0.01;
      RI, 1.57+/-0.24, p < 0.05) although nitrate + nitrite (31.8+/-4.1 micromol/L) and
      %NO2-Tyr (1.15%+/-0.20%) were significantly lower in group A than in group B
      (nitrate + nitrite, 50.2+/-5.0 micromol/L, p < 0.01; %NO2-Tyr, 1.46%+/-0.21%, p <
      0.01). Western immunoblot analysis from lung tissue of group A identified marked
      iNOS inhibition without inhibiting endothelial-constitutive NOS, and neutrophil
      accumulation in the lung specimens was significantly greater in group A (6.5+/
      0.7/alveoli) than in group B (4.4+/-0.4/alveoli, p < 0.01). CONCLUSIONS: These
      results suggest that NO production from iNOS may be an adaptive response for
      attenuating the CPB-induced inflammatory response.

PMID- 11465171
TI  - Impacts of pulsatile systemic circulation on endothelium-derived nitric oxide
      release in anesthetized dogs.
AB  - BACKGROUND: The effects of pulsatile flow on endothelium-derived nitric oxide
      mediated vasodilation are not fully elucidated in an in vivo model. METHODS: A
      left ventricular assist device was established in 10 anesthetized dogs with a
      centrifugal pump and an air-driven pneumatic pump. The systemic circulation was
      subjected to step changes in the frequency of pulse (0, 30, 60, and 120 bpm with
      a fixed pulse pressure of 50 mm Hg), and in the amplitude of pulse (0, 20, and 50
      mm Hg with a fixed pulse rate of 120 bpm). Hemodynamic variables and calculated
      total systemic vascular resistance were compared before and after the
      administration of N(G)-Nitro-L-arginine Methyl Ester (L-NAME) (20 mg/kg). Plasma
      NO2-/NO3- concentration levels were also measured. RESULTS: Total systemic
      vascular resistance significantly decreased while plasma NO2-/No3- concentration
      increased in response to the rise in both pulse rate and pulse pressure. However,
      L-NAME significantly diminished these effects of pulsatile flow. CONCLUSIONS:
      Both the frequency and the amplitude of pulse wave in the systemic circulation
      are significant independent stimuli for endothelium-derived nitric oxide-mediated
      vasodilation in vivo.

PMID- 11465172
TI  - Is chronically dysfunctional yet viable myocardium distal to a severe coronary
      stenosis hypoperfused?
AB  - BACKGROUND: Controversy exists regarding the perfusion status of chronically
      dysfunctional yet viable myocardium. Studies investigating the pathophysiology of
      this condition have reached different conclusions, with some suggesting that
      myocardial blood flow (MBF) in these regions is normal at rest with regional
      dysfunction resulting from repetitive stress-induced ischemia (stunned
      myocardium), whereas others have proposed that MBF is chronically reduced at rest
      (hibernating myocardium). However, adequately powered experimental studies
      investigating this question in an appropriate animal model using clinically
      available techniques have not been performed. Based on the mixed results of prior
      studies, we hypothesized that these chronically dysfunctional yet viable regions
      may actually represent a mixture of hibernation and stunning. Consequently, the
      purpose of this study was to quantitatively determine the distribution of MBF in
      left ventricular regions with chronically impaired resting function but preserved
      viability in a large population of animals with single-vessel coronary stenosis
      in an attempt to further elucidate the mechanism(s) responsible for chronic,
      reversible myocardial dysfunction. METHODS: Fifty-two adult mini-swine with 90%
      proximal left circumflex (LCx) stenosis underwent dynamic positron emission
      tomography (PET) with 13N-ammonia and 18F-fluorodeoxyglucose and dobutamine
      stress echocardiography (DSE) (5 to 40 microg/kg/min) 1 month after stenosis
      creation. Values of MBF and FDG uptake by PET and wall motion score index (WMSI)
      by DSE were compared using a standard 16-segment model. RESULTS: Of 312 possible
      LCx segments seen on PET, 303 (97.1%) were visualized by DSE. Of the 303 LCx
      segments, 279 (92.1%) had rest dysfunction (WMSI > or = 2) by DSE. One hundred
      eighty-two segments (60.1%) had decreased (< 85% reference) MBF at rest with
      preserved to increased (> 60% reference) FDG uptake and were classified as
      hibernating. Ninety-two segments (30.4%) had preserved MBF (> or = 85% reference)
      and were classified as stunned. Five segments (1.7%) with reduced (< or = 60%
      reference) FDG uptake by PET and akinesis or dyskinesis at rest (WMSI > or = 3)
      and no contractile reserve were considered infarcted. Hibernating segments had
      significantly higher FDG uptake at rest (360.7+/-48.3 vs 212.3+/-17.7% septal
      values; p < 0.001) than stunned segments consistent with greater resting
      ischemia. Likewise, mean rest WMSI was also worse in hibernating versus stunned
      segments (2.35+/-0.04 vs 2.13+/-0.04; p < 0.001). There was no difference in the
      percentage of hibernating versus stunned segments exhibiting contractile reserve
      during dobutamine infusion (55.5 vs 63.7%; p = 0.4), indicating similar degrees
      of viability. CONCLUSIONS: Myocardial hibernation and stunning appear to
      frequently coexist in regions served by a stenotic coronary vessel. Hibernating
      regions appear to have greater resting ischemia based on higher values of FDG
      uptake and greater resting dysfunction. Reversible left ventricular dysfunction
      in the setting of chronic coronary artery disease is likely due to a combination
      of these two mechanisms.

PMID- 11465173
TI  - Assessment of mortality rates for congenital heart defects and surgeons'
      performance.
AB  - BACKGROUND: In the absence of reliable national data, we have collected results
      of all operations for congenital heart defects from five departments to assess
      mortality rates and compare them among surgeons and departments. METHODS: Data
      relating to all operations (2,718) carried out at the five centers during a
      period from April 1, 1997 through March 31, 1999. Clearly defined criteria were
      agreed for the classification of patients into various subgroups. RESULTS: The
      overall hospital mortality was 4.4% (95% confidence intervals 3.7%-5.3%).
      Mortality for open-operations was 12.6% in neonates, 5.1% in infants, and 3.5% in
      children. Mortality rates were 1.1% for coarctation, 0.4% ventricular septal
      defect, 4.1% atrioventricular septal defect, 2.9% Fallot, 0.9% switch, and 15.6%
      truncus arteriosus. Although individual surgeons' mortality rates ranged from
      1.8% to 7.5%, none of the 12 surgeons' data were above 95% confidence intervals.
      For individual surgeons, the change in mortality rates between the 2 years ranged
      between -3.3% and +3.8%. CONCLUSIONS: With 2 years' data available, estimates of
      mortality rates are more precise as reflected by tighter confidence intervals.
      There were relatively small data sets for individual hospitals and surgeons,
      which made statistical evaluation difficult. For setting standards, data from
      more departments for a longer period will be required. Statistical methods alone
      cannot be used as a sole arbiter of what is considered acceptable performance.

PMID- 11465174
TI  - Modified Lecompte procedure for the anomalies of ventriculoarterial connection.
AB  - BACKGROUND: The Lecompte procedure for correcting transposition of the great
      arteries has an advantage because it obviates the need for an extracardiac
      conduit for the reconstruction of the pulmonary outflow tract. In this study, we
      evaluated the effectiveness and the application of the Lecompte procedure based
      on our experiences. METHODS: A retrospective review was conducted of the records
      of 45 patients who underwent the Lecompte procedure during the past 11 years to
      achieve direct right ventricle to pulmonary artery continuity. Mean age at
      operation was 2.4+/-1.7 years (range 3.5 months to 6.9 years). The diagnoses
      involved anomalies of the ventriculoarterial connection with ventricular septal
      defect and pulmonary outflow tract obstruction, such as transposition of the
      great arteries, double-outlet right ventricle, and double-outlet left ventricle.
      RESULTS: Early mortality was 4.4% (2 of 45 patients) and late mortality was 4.7%
      (2 of 43). The mean follow-up was 4.9+/-3.1 years. Fourteen patients (34.1% of
      survivors, n = 41) had pulmonary stenosis (pressure gradient above 30 mm Hg), the
      main reason for which was a calcified monocusp valve (n = 10, 71.4%). Eight of 45
      patients (17.8%) underwent reoperation: 2 for residual ventricular septal defect,
      1 for recurrent septic vegetation, and 5 for pulmonary stenosis. The cumulative
      survival rates were 91.1%+/-4.2% at 10 years. The actuarial probabilities of
      freedom from reoperation for pulmonary stenosis were 93.8%+/-4.3% and 71.4%+/
      11.8% at 5 and 10 years, respectively. CONCLUSIONS: Our review suggests that the
      Lecompte procedure is an effective treatment modality for anomalies of the
      ventriculoarterial connection with ventricular septal defect and pulmonary
      outflow tract obstruction. Repair in early age is possible with acceptable
      morbidity and mortality, but recurrent right ventricular outflow tract
      obstruction caused by degeneration of the monocusp valve is a problem that needs
      resolution.

PMID- 11465175
TI  - Atrioventricular valve replacement in patients with a single ventricle.
AB  - BACKGROUND: Significant atrioventricular valve (AVV) insufficiency has been
      associated with increased mortality and morbidity in patients with single
      ventricle. Although many patients can be managed with valvuloplasty alone, some
      patients require AVV replacement. The optimal timing, outcome, and risk factors
      for AVV replacement in this population have not been described. METHODS: We
      retrospectively reviewed our experience with AVV replacement in patients with
      single ventricle from January 1984 to August 2000. Outcome variables included
      mortality and valve-related complications. RESULTS: Seventeen patients required
      AVV replacement. Prosthetic valve types included: St. Jude's valve in 14, Bjork
      Shiley in 1, Hall-Kaster in 1, and Carpentier-Edwards in 1. Valve size ranged
      from 17 to 33 mm, Median age at valve replacement was 3.0 years (range 7 days to
      17.3 years). Of the 16 subjects with normal atrioventricular conduction
      preoperatively, 7 (44%) developed postoperative complete heart block. Hospital
      mortality was 29%. Hospital mortality decreased significantly from 56% in 1984 to
      1993 to no deaths from 1994 to 2000 (p = 0.03). Younger age (less than 2 years)
      at operation was also a risk factor for hospital mortality (p = 0.03). There were
      four late deaths in this series and 1 patient underwent heart transplantation. Of
      the surviving patients, none has required replacement of the prosthetic valve. No
      patients have had cerebrovascular accident subsequent to AVV replacement.
      Functional status is New York Heart Association functional class I in 5, class II
      in 1, and Class III in 1. CONCLUSIONS: Atrioventricular valve replacement can be
      performed in patients with single ventricle with acceptable morbidity and
      mortality. The development of postoperative complete heart block is common.
      Survival after AVV replacement has improved in recent years, and intervention
      before patients develop ventricular dysfunction and atrial arrhythmias may
      further improve outcome.

PMID- 11465176
TI  - Cerebral oxygen saturation before congenital heart surgery.
AB  - BACKGROUND: In congenital heart disease (CHD), neurologic abnormalities
      suggestive of hypoxia-ischemia are often apparent before cardiac surgery. To
      evaluate preoperative cerebral oxygenation, this study determined cerebral O2
      saturation (ScO2) in CHD and healthy children. METHODS: Ninety-one CHD and 19
      healthy children aged less than 7 years were studied before surgical or
      radiologic procedures. Arterial saturation (SaO2) and ScO2 were measured by pulse
      oximetry and near infrared cerebral oximetry. Cerebral O2 extraction (CEO2) was
      calculated (SaO2-ScO2). SaO2, ScO2, and CEO2 were compared among diagnoses.
      Multivariable regression was performed between ScO2 and clinical variables.
      RESULTS: In healthy subjects, ScO2 (68%+/-10%) and CEO2 (30%+/-11%) were similar
      to patients with ventricular septal defect, aortic coarctation, and single
      ventricle after Fontan operation. ScO2 was significantly decreased in patients
      with patent ductus arteriosus (53%+/-8%), tetralogy of Fallot (57%+/-12%),
      hypoplastic left heart syndrome (46%+/-8%), pulmonary atresia (38%+/-6%), and
      single ventricle after aortopulmonary shunt (50%+/-7%), or bidirectional Glenn
      operation (43%+/-6%). CEO2 was significantly different only in patent ductus
      arteriosus (46%+/-8%) and hypoplastic left heart syndrome (38%+/-12%). In
      multivariable regression, only SaO2 was related to ScO2 (R = 0.63, p < 0.001).
      CONCLUSIONS: Cerebral oxygenation in CHD varies with anatomy and arterial
      saturation, and in some patients, it is very low compared with healthy subjects.

PMID- 11465177
TI  - Chylopericardium after cardiac operations in children.
AB  - BACKGROUND: Chylopericardium is a rare complication after operation for
      congenital heart disease. The incidence and clinical outcomes in a large cohort
      of surgical patients are unknown. METHODS: We retrospectively reviewed the
      clinical records spanning more than 12 years in a single institution of 16
      children with chylopericardium after cardiac operation. RESULTS: We identified 16
      patients with chylopericardium between 1985 and 1997. Chylopericardium was
      isolated in 7 patients. Twelve patients required pericardial drainage. Patients
      with isolated chylopericardium presented late and were treated initially as
      having postpericardiotomy syndrome. Three patients underwent thoracic duct
      ligation. There were two late deaths unrelated to the chylothorax. Associated
      diagnoses were internal jugular vein thrombosis and recurrent pulmonary vein
      obstruction (1 of 16 patients), an associated syndrome but not Turner or Noonan
      (10 of 16), superior cavopulmonary or total cavopulmonary anastomosis (7 of 16),
      atrioventricular septal defect repair (5 of 16), and repair of tetralogy of
      Fallot (2 of 16). CONCLUSIONS: Percutaneous drainage to relieve tamponade
      together with a low-fat or medium-chain triglyceride diet results in resolution
      in most cases of postoperative chylopericardium. If a pericardial effusion
      enlarges, fails to clear on aspirin therapy, or presents late after hospital
      discharge, diagnostic pericardial tap and a low-fat diet are indicated.

PMID- 11465178
TI  - Predictors of outcome in thymectomy for myasthenia gravis.
AB  - BACKGROUND: Factors determining predictability of response to thymectomy for
      myasthenia gravis (MG) vary in the literature. METHODS: A 25-year retrospective
      review (1974 to 1999) of all thymectomies performed at a single institution was
      undertaken. RESULTS: In 113 consecutive thymectomies for MG, women comprised 79%
      (89 of 113 patients), and mean age was 40+/-15 years. Complications occurred in
      14% of patients (16 of 113). In-hospital mortality was 0, but 90-day hospital
      mortality was 0.88% (1 of 113 patients). Follow-up was obtained in 81% (92 of 113
      patients) at a mean of 51+/-59 months postoperatively. Complete remission was
      achieved in 21% of patients (19 of 92), and marked improvement of MG in 54% (50
      of 92), for a total benefit rate of 75%. Fourteen percent (13 of 92) were
      unchanged, and 11% (10 of 92) were worse. Using univariate analysis, sex, age,
      and pathology correlated significantly with outcome (p < 0.05): 80% of women (57
      of 70) benefited from the procedure, versus 57% of men (12 of 21). Eighty percent
      (57 of 70) of patients less than 51 years of age were improved or in remission,
      versus 57% (12 of 22) older than 50. Twenty-three percent (5 of 22) of patients
      with thymoma deteriorated, versus 7.1% (5 of 70) without thymoma. Sex did not
      significantly correlate in the multivariate model. CONCLUSIONS: Sex, age, and
      thymic pathology are potential predictors of outcome in thymectomy for MG, and
      may shape treatment decisions and target higher-risk patients.

PMID- 11465179
TI  - Durability of combined aortic and mitral valve repair.
AB  - BACKGROUND: This study was undertaken to determine the durability of combined
      aortic and mitral valve repair. METHODS: From 1979 through 1999, 158 patients
      underwent simultaneous aortic and mitral valve repair. Multivariable, multi-phase
      hazard function analysis was used to determine risk factors for the outcomes of
      death and reoperation. RESULTS: Hospital mortality was 3%. Survival after
      operation was 97%, 93%, 82%, and 62% after 30 days and 1, 5, and 10 years,
      respectively. Risk factors for late death included aortic stenosis (p = 0.0001),
      older age (p = 0.002), and abnormal left ventricular function (p = 0.007). Thirty
      six patients required reoperation for valvular dysfunction, and freedom from
      reoperation was 94%, 82%, and 65% after 1, 5, and 10 years, respectively. Risk
      factors for reoperation included severe aortic regurgitation (p = 0.004), aortic
      cusp shaving (p = 0.05), mitral valve chordal transfer (p = 0.004), and bovine
      pericardial annuloplasty (p = 0.002). Five-year freedoms from endocarditis,
      thromboembolism, and hemorrhage were 97%, 98%, and 99%, respectively, with
      freedom from any of these valve-related morbidities of 99%, 95%, and 94% after 1,
      5, and 10 years, respectively. CONCLUSIONS: Double valve repair is associated
      with acceptable late survival and excellent freedom from valve-related morbidity,
      but limited durability. Therefore, double valve repair should be reserved for
      patients who cannot be anticoagulated, and should be used with caution in
      patients with aortic stenosis, rheumatic valve disease, or anterior mitral
      leaflet pathology.

PMID- 11465180
TI  - Thymoma: trends over time.
AB  - BACKGROUND: This is a review of a series of patients who presented with thymoma
      over the most recent 20-year period. Changes and trends in disease patterns were
      documented. METHODS: Data were collated retrospectively but all pathology slides
      were reviewed. Survival functions were estimated using the Kaplan-Meier method.
      RESULTS: Seventy-one patients had a partial or total thymectomy during this
      period for a thymoma. Average age was 55 years. Twenty-three patients (32%) had
      myaesthenia gravis. Eighteen patients (25%) were asymptomatic. Thirty-three
      patients (47%) had stage 1 disease. Complete resection was achieved in 60
      patients (85%). Five-year survival was 88%. Fifty percent of patients with
      myesthenia gravis showed improvement in symptoms. CONCLUSIONS: Five- and 10-year
      survival rates in this study are better than in other series. We attribute this
      to an increasing number of patients with stage 1 and stage 2 disease,
      particularly those with myasthenia gravis who now have screening computer
      tomography, and also to the surgical intent of aiming to achieve complete
      resection even if excision of adjacent tissue is required.

PMID- 11465181
TI  - Expanded indications for transcervical thymectomy in the management of anterior
      mediastinal masses.
AB  - BACKGROUND: Transcervical thymectomy (TCT) is an accepted though controversial
      approach for thymectomy in myasthenia gravis (MG). The suggestion of thymoma on
      computed tomography (CT) has been considered a contraindication to TCT. We sought
      to determine whether the indications for TCT could be safely expanded to include
      selected patients with thymomas as well as other types of anterior mediastinal
      masses. METHODS: Between January 1992 and September 1999, we performed 121 TCTs:
      98 in patients with MG and 23 in patients without MG. The patients' records were
      retrospectively reviewed. RESULTS: Among the 98 MG patients, 28 had CT scans
      suspicious for thymoma. Of these, 14 had a thymoma pathologically. These were
      classified as stage I (5), stage II (8), and stage III (1). Five patients
      required extension of the incision for completion of the procedure. There have
      been no thymoma recurrences to date with a mean follow-up of 48 months (range 3
      to 96 months). In the 23 patients without MG, 12 had new anterior mediastinal
      masses, 4 had a history of treated lymphoma, 1 had a history of treated germ cell
      tumor, and 6 had suspected mediastinal parathyroid adenoma. Diagnostic tissue was
      obtained in all patients undergoing the procedure for diagnosis, and in 4 of 6
      patients, a parathyroid adenoma was successfully resected. CONCLUSIONS:
      Transcervical exploration and thymectomy offers a less invasive approach to the
      diagnosis and/or definitive treatment of selected anterior mediastinal masses. We
      suggest that it is appropriate to expand its use to several clinical scenarios
      beyond the typical indication of thymectomy in MG patients without thymoma.

PMID- 11465182
TI  - Predictors of survival for esophageal cancer patients with and without celiac
      axis lymphadenopathy: impact of staging endosonography.
AB  - BACKGROUND: Esophageal cancer patients with M1a disease are reported to have poor
      survival. We hypothesized that patients with celiac lymph node metastases (CLN)
      identified by endoscopic ultrasonography (EUS) would predict a cohort with
      significantly worse survival postoperatively. Accurate preoperative
      identification of this group will facilitate future adjuvant studies. METHODS:
      During the study period, 211 patients with esophageal cancer underwent EUS
      staging. Patients with evaluable celiac axis (n = 182) were included in this
      study. Survival of patients with and without CLNs was compared and the factors
      affecting overall survival were assessed. A subgroup analysis based on CLN status
      was performed in the subgroup of patients who underwent surgical procedures.
      RESULTS: Follow-up data was available in 91.2% (166 of 182) of the patients. As
      staged by EUS, T1, T2, T3, and T4 tumors accounted for 9.3%, 11.5%, 56%, and 21%
      of the cases, respectively. At least one CLN was imaged by EUS in 40% (72 of
      182). The 5-year survival in patients with CLNs detected by EUS was 13% (95%
      confidence interval, 5% to 21%) compared with 30% (95% confidence interval, 21%
      to 40%) in patients with no CLNs detected by EUS (p = 0.007). In the subgroup of
      patients who underwent surgical procedures (n = 68), patients with CLN
      involvement had worse survival compared with those who did not have malignant
      involvement of CLNs at the time of their operation (median survival 39.8 versus
      13.8 months, p = 0.0008). In a Cox proportional model, adjusting for race and the
      type of therapy, patients with CLN involvement or advanced EUS American Joint
      Committee on Cancer stage were more likely to have worse survival (p < 0.05)
      CONCLUSIONS: EUS base line findings correlate with long term survival in patients
      with esophageal cancer. Patients with M1a disease as identified by EUS had a
      significantly worse postoperative survival when compared with non-M1a patients.
      This cohort of patients will be ideal for the study of induction therapy since
      the effect of down staging can be assessed before operation.

PMID- 11465183
TI  - Benign tracheo-neo-esophageal fistulas after subtotal esophagectomy.
AB  - BACKGROUND: Benign tracheo-neo-esophageal fistulas after esophagectomy are rare
      and treatment can be challenging. They can result from perioperative tracheal
      injury or various postoperative complications. METHODS: Charts of 6 patients with
      a benign tracheoneo-esophageal fistula after subtotal esophagectomy treated in
      this institution between July 1993 and August 1999 were analyzed. RESULTS: Three
      men and 3 women (median age 61 years) developed a fistula after subtotal
      esophagectomy. Symptoms varied from mild swallowing difficulties to aspiration
      pneumonia and mediastinitis. Two patients with mild symptoms were treated
      conservatively. In 1 patient a long fistula was partly excised through the neck.
      In 3 patients the gastric tube was excluded or excised, with surgical closure of
      the tracheal defect. The alimentary tract was reconstructed by colonic
      interposition. There were no major complications. After a median follow-up of 1.6
      years, all fistulas were closed. All patients were capable of sufficient oral
      intake. CONCLUSIONS: A benign tracheo-neo-esophageal fistula after esophagectomy
      is a rare, but serious complication. Site and size of the fistula, together with
      the severity of symptoms, should dictate management.

PMID- 11465184
TI  - Value of systematic mediastinal lymph node dissection during pulmonary
      metastasectomy.
AB  - BACKGROUND: Systematic mediastinal lymph node dissection is the accepted standard
      when curative resection of bronchial carcinoma is performed. However, mediastinal
      lymph node dissection is not routinely performed with pulmonary metastasectomy,
      in which only enlarged or suspicious lymph nodes are removed. The incidence of
      malignant infiltration of mediastinal lymph nodes in patients with pulmonary
      metastases is not known. METHODS: Sixty-three patients who underwent 71
      resections through a thoracotomy for pulmonary metastases of different primary
      tumors were studied prospectively. Selected patients showed no evidence of tumor
      progression or extrathoracic metastases and pulmonary metastasectomy was planned
      with curative intent. All patients underwent preoperative helical computed
      tomography (CT) scanning. Only patients with no evidence of suspicious
      mediastinal lymph nodes on the CT scan (less than 1 cm in the short axis) were
      included in this study. A mediastinal lymph node dissection was performed
      routinely with metastasectomy. RESULTS: In 9 patients (14.3%) at least one
      mediastinal lymph node revealed malignant cells in accordance with the resected
      metastases. When compared with the preoperative CT scan, additional pulmonary
      metastases were detected in 16.9% of performed operations. There was a trend
      toward an improved survival rate in patients without involvement of the
      mediastinal lymph nodes. The number of pulmonary metastases had no influence on
      survival. CONCLUSIONS: On a patient-by-patient basis, the frequency of
      misdiagnosed mediastinal lymph node metastases is about the same as compared with
      non-small cell bronchial carcinomas. Systematic mediastinal lymph node dissection
      reveals a significant number of patients, who otherwise are assumed free of
      residual tumor. The knowledge of metastases to mediastinal lymph nodes after
      complete resection of pulmonary metastases could influence the decision for
      adjuvant therapy in selected cases.

PMID- 11465185
TI  - Outcome of thoracoscopic pulmonary metastasectomy evaluated by confirmatory
      thoracotomy.
AB  - BACKGROUND: The aim of this study was to determine the feasibility, accuracy, and
      outcome of thoracoscopic resection of peripherally located pulmonary metastases.
      METHODS: The 28 patients had three or fewer solitary metastases, located in the
      periphery of the lung, with a diameter 3 cm or less on computed tomography scan.
      A thoracoscopic resection was performed to remove all identified lesions
      evaluated by confirmatory thoracotomy. RESULTS: A thoracoscopic resection was
      technically impossible in 10 patients. In 1 patient a confirmatory thoracotomy
      was not performed because the lesion was diagnosed as carcinoid. Among the 17
      patients who underwent confirmatory thoracotomy, 12 patients had a complete
      thoracoscopic resection and 5 patients had residual disease. The success rate
      appeared to be higher (p = 0.01) in patients with one lesion (11 of 12 patients),
      than in patients with more than one lesion (1 of 5 patients) found by
      preoperative computed tomography scan. CONCLUSIONS: Thoracoscopic resection can
      be considered a viable treatment option for patients who present with a solitary
      pulmonary metastasis with a diameter of 3 cm or less, when the lesion is located
      in the periphery of the lung.

PMID- 11465186
TI  - Percutaneous venovenous perfusion-induced systemic hyperthermia for advanced non
      small cell lung cancer: initial clinical experience.
AB  - BACKGROUND: Venovenous perfusion-induced systemic hyperthermia raises core body
      temperature by extracorporeal heating of the blood. Five patients with advanced
      non-small cell lung carcinoma stage IV (4.4+/-1 months after initial diagnosis)
      received venovenous perfusion-induced systemic hyperthermia to 42.5 degrees C
      (core temperature) to assess technical and patient risks. METHODS: After general
      anesthesia and systemic heparinization (activated clotting time > 300 seconds),
      percutaneous cannulation of the right internal jugular vein (15F) for drainage
      and common femoral vein (15F) for reinfusion allowed extracorporeal flow rates up
      to 1,500 mL/min (20 mL x kg(-1) x min(-1)) with the ThermoChem System. This
      device uses charcoal-based sorbent for electrolyte homeostasis. Six monitored
      sites (rectal, bladder, tympanic x2, nasopharyngeal, and esophageal) determined
      average core temperature. RESULTS: All patients achieved a core target
      temperature of 42.5 degrees C for 2 hours. Electrolyte balance was maintained
      throughout hyperthermia (mean) in mmol/L: Na+, 136.2+/-2.2 mmol/L; K+, 4.0+/-0.3
      mmol/L; Ca2+, 4.1+/-0.2 mg/dL; Mg2+, 1.9+/-0.1 mg/dL; PO4-, 4.5+/-0.9 mg/dL).
      Plasma cytokine concentration revealed significant heat-induced activation of
      proinflammatory and antiinflammatory cascades. All patients exhibited systemic
      vasodilation requiring norepinephrine infusion, 4 of 5 patients required vigorous
      diuresis, and 3 of 5 required intubation for 24 to 36 hours because of pulmonary
      edema or somnolence, with full recovery. Average length of hospital stay was 5.4
      days. Serial tumor measurements (1 patient withdrew) revealed a decrease (64.5%+/
      18%) in tumor size in 2 patients, no change in 1, and enlargement in 1, with no
      30-day mortality. Median survival after hyperthermia treatment was 172 days
      (range, 40 to 271 days). CONCLUSIONS: Venovenous perfusion-induced systemic
      hyperthermia is feasible and provides the following potential advantages for
      better tumoricidal effect: (1) homogeneous heating, and (2) a higher sustained
      temperature.

PMID- 11465187
TI  - Empyema and bronchopleural fistula after pneumonectomy: factors affecting
      incidence.
AB  - BACKGROUND: Factors affecting the incidence of empyema and bronchopleural fistula
      (BPF) after pneumonectomy were analyzed. METHODS: All patients who underwent
      pneumonectomy at the Mayo Clinic in Rochester, Minnesota, from January 1985 to
      September 1998 were reviewed. There were 713 patients (514 males and 199
      females). Ages ranged from 12 to 86 years (median 64 years). Indication for
      resection was primary malignancy in 607 patients (85.1%), metastatic disease in
      32 (4.5%), and benign disease in 74 (10.4%). One hundred fifteen patients (16.1%)
      underwent completion pneumonectomy. Factors affecting the incidence of
      postoperative empyema and BPF were analyzed using univariate and multivariate
      analysis. RESULTS: Empyema was documented in 53 patients (7.5%; 95% confidence
      interval [CI], 5.7% to 9.7%) and a BPF in 32 (4.5%; 95% CI, 3.1% to 6.3%).
      Univariate analysis demonstrated that the development of empyema was adversely
      affected by benign disease (p = 0.0001), lower preoperative forced expiratory
      volume in 1 second (FEV1; p < 0.01) and diffusion capacity of lung to carbon
      monoxide (DLCO; p = 0.0001), lower preoperative serum hemoglobin (p = 0.05),
      right pneumonectomy (p = 0.0109), bronchial stump reinforcement (p = 0.007),
      completion pneumonectomy (p < 0.01), timing of chest tube removal (p = 0.01), and
      the amount of blood transfusions (p < 0.01). Similarly, the development of BPF
      was significantly associated with benign disease (p = 0.03), lower preoperative
      FEV1 (p = 0.03) and DLCO (p = 0.01), right pneumonectomy (p < 0.0001), bronchial
      stump reinforcement (p = 0.03), timing of chest tube removal (p = 0.004),
      increased intravenous fluid in the first 12 hours (p = 0.04), and blood
      transfusions (p = 0.04). Bronchial stump closure with staples had a protective
      effect against BPF compared with suture closure (p = 0.009). No risk factors were
      identified as being jointly significant in multivariate analysis. CONCLUSIONS:
      Multiple perioperative factors were associated with an increased incidence of
      empyema and BPF after pneumonectomy. Prophylactic reinforcement of the bronchial
      stump with viable tissue may be indicated in those patients suspected at higher
      risk for either empyema or BPF.

PMID- 11465188
TI  - Repair of total anomalous pulmonary venous connection without cardiopulmonary
      bypass.
AB  - Two infants with asplenia syndrome and pulmonary venous obstruction underwent
      repair of total anomalous pulmonary venous connection without cardiopulmonary
      bypass in 1988. Using a side-biting clamp, an anastomosis between the left upper
      pulmonary vein and left superior vena cava-atrial junction was satisfactorily
      created without undue instability. Furthermore, both cases had the advantage of
      efficient growth in the anastomotic site postoperatively.

PMID- 11465189
TI  - Emergency pulmonary autograft mitral valve replacement in a child.
AB  - Mitral valve replacement in small children imposes significant clinical
      difficulties because of the relatively small mechanical prosthetic valves
      required and the need for lifelong anticoagulation therapy. A child weighing 10.4
      kg presented with thrombosis of her 19-mm mechanical mitral prosthesis 4 weeks
      after implantation despite appropriate oral anticoagulation therapy. An emergency
      mitral valve replacement with a pulmonary autograft was successfully performed
      with encouraging short-term results.

PMID- 11465190
TI  - Traumatic disruption of the ascending aorta in a child after heart transplant.
AB  - We report a traumatic disruption of the ascending aorta in an 8-year-old boy who
      had undergone orthotopic cardiac transplant at 6.5 years of age for congenital
      heart block and dilated cardiomyopathy. At presentation his aortic injury was not
      immediately recognized, but persistence in identifying and confirming a
      suspicious aortic rupture was lifesaving.

PMID- 11465191
TI  - Partial mitral valve replacement for acute endocarditis.
AB  - We present a case of acute endocarditis involving the posteromedial commissure
      and both leaflets of the mitral valve, including a vegetation on and perforation
      of the anterior leaflet, in a young man with active Crohn's disease. Repair was
      performed using glutaraldehyde-treated bovine pericardium. Competence of the
      valve was achieved with no recurrence of endocarditis. This case demonstrates
      that extensive destruction of both leaflets of the mitral valve does not prohibit
      repair.

PMID- 11465192
TI  - Traumatic papillary muscle rupture.
AB  - Papillary muscle rupture caused by blunt chest trauma is a relatively rare cause
      of mitral incompetence. To date only 25 cases of surgically corrected
      posttraumatic mitral regurgitation have been reported, of which only eight
      resulted from rupture of the anterolateral papillary muscle.

PMID- 11465193
TI  - An unusual case of bioprosthetic mitral valve thrombosis.
AB  - Bioprosthetic valve thrombosis and related embolism are considered extremely
      unlikely, thus allowing most patients to avoid long-term anticoagulation. There
      is, however, limited experience in the diagnosis and treatment of such a
      condition. We present the case of a patient with a porcine mitral bioprosthesis
      who presented with acute thrombosis with unusual echocardiographic features. A
      favorable outcome was observed after conventional anticoagulant treatment.

PMID- 11465194
TI  - Implantable cardioverter defibrillator patch erosion in a heart transplant
      patient.
AB  - A 57-year-old man who had received an automatic implantable cardioverter
      defibrillator and subsequent orthotopic heart transplant presented to medical
      attention for hemoptysis. The hemoptysis was caused by the migration of the left
      ventricular patch of the automatic implantable cardioverter defibrillator, which
      had been left in place at the time of orthotopic heart transplant. The patch had
      eroded into the left lung. We recommend that implantable cardioverter
      defibrillators be removed completely at the time of heart transplantation to
      prevent subsequent complications.

PMID- 11465195
TI  - Pseudoaneurysm after heart transplantation with history of LVAD driveline
      infection.
AB  - An infective complication of the aorta is a potential cause of early and late
      mortality after heart transplantation. We report the case of a 21-year-old male
      cardiac transplant patient in whom a pseudoaneurysm of the recipient site of
      ascending aorta coincided with the site of the outflow prosthesis of a
      preexisting left ventricular assist device; this condition developed 9 months
      after transplantation.

PMID- 11465196
TI  - Varix of the heart.
AB  - A 76-year-old patient was operated on for an asymptomatic primary tumor of the
      heart located in the right atrium. The tumor was detected during a preanesthetic
      check-up for a transurethral resection of a prostate adenoma, showing a 3/6
      systolic murmur. The mass was resected. The postoperative course was uneventful
      but the histologic result was surprising: varix of the heart.

PMID- 11465197
TI  - Successful resuscitation of acute massive pulmonary embolism with extracorporeal
      membrane oxygenation and open embolectomy.
AB  - Acute massive pulmonary embolism is usually fatal if not treated aggressively,
      but the management is not standardized. Open pulmonary embolectomy retains a role
      in the treatment of this disastrous disease. Extracorporeal membrane oxygenation
      has been used for cardiopulmonary support in some patients with life-threatening
      pulmonary embolism. This article details our experience of a 58-year-old woman
      suffering from acute cardiopulmonary collapse caused by massive pulmonary
      embolism. Under extracorporeal membrane oxygenation support, the patient received
      pulmonary angiography and underwent open embolectomy for a definitive treatment.

PMID- 11465198
TI  - Total esophageal reconstruction using a tubed parascapular free flap.
AB  - A method for total esophageal reconstruction when intestinal options are no
      longer available is presented. The technique described utilizes the parascapular
      microsurgical free flap, which is tubed and interposed between the cervical
      esophagus and the gastric remnant in the abdomen. The technique involves a well
      recognized microsurgical flap and may be added to the armamentarium for total
      esophageal reconstruction.

PMID- 11465199
TI  - Synchronous primary lung carcinoma and lung metastasis from extrathoracic
      carcinoma.
AB  - We present the cases of 2 patients in whom primary lung cancer was found
      unexpectedly when pulmonary resection was performed for metastatic lung cancer.
      The possibility of combined primary and metastatic carcinoma should be considered
      in patients with a diagnosis of multiple pulmonary metastases from extrathoracic
      tumor.

PMID- 11465200
TI  - Nitric oxide for the treatment of postpneumonectomy pulmonary edema.
AB  - Inhaled nitric oxide, a selective pulmonary vasodilator, has been used to improve
      arterial oxygenation in adult respiratory distress syndrome. To our knowledge, it
      has not been successfully used to treat this syndrome after major lung resection.
      We used nitric oxide to treat postpneumonectomy pulmonary edema with immediate
      and sustained improvement in oxygenation. The patient was successfully weaned
      from nitric oxide and extubated after 3 days of supportive therapy.

PMID- 11465201
TI  - Contralateral pulmonary artery stenosis after left pneumonectomy.
AB  - Contralateral pulmonary artery stenosis is a rare complication following
      pneumonectomy. When extensive intrapericardial dissection is warranted, one must
      be wary of this potential complication and take measures to avoid it.
      Postoperatively, a high index of suspicion must be maintained in a patient with a
      new onset of right-sided heart failure after intrapericardial pneumonectomy. We
      discuss intraoperative risk factors, postoperative clinical findings, and our
      strategy for repair.

PMID- 11465202
TI  - The use of a Dumon stent for the treatment of a bronchopleural fistula.
AB  - We report the successful management of a bronchopleural fistula with bronchial
      stent placement combined with irrigation of the empyema cavity. A bronchopleural
      fistula occurred in a 67-year-old man after a right upper lobectomy for lung
      cancer. Resuturing of the bronchial stump plus omental wrapping and subsequent
      closure of the open stump with a pedicled flap of intercostal muscle were not
      effective. Consequently, we placed a Dumon stent in the right main bronchus to
      close the stump.

PMID- 11465203
TI  - Massive hemoptysis from a lung abscess due to retained gallstones.
AB  - This case report describes a subhepatic abscess from spilled gallstones which
      eroded through the diaphragm causing a right lower lobe pulmonary abscess and
      presenting as massive hemoptysis.

PMID- 11465204
TI  - Aortic root replacement versus aortic valve replacement: a case-match study.
AB  - BACKGROUND: There is increasing evidence that patients with aortic valve disease
      and dilatation of the ascending aorta are at risk for later dissection or rupture
      of the aortic wall when the dilated ascending aorta is not replaced or reinforced
      at the time of aortic valve replacement. In order to find out whether the more
      complex surgical procedure of aortic root replacement carries a higher early or
      late postoperative risk than isolated aortic valve replacement, we conducted a
      matched-pair study with patients of both groups. METHODS: Between June 1993 and
      August 1998, 100 consecutive patients with aortic valve disease and
      ectasia/aneurysm of the ascending aorta underwent replacement of the aortic valve
      and the ascending aorta with a CarboSeal composite graft (CarboSeal; Sulzer Carbo
      Medics Inc, Austin, TX). Identical bileaflet valve prostheses (CarboMedics;
      Sulzer CarboMedics Inc, Austin, TX) were implanted during the same time period in
      928 patients for aortic valve disease. On the basis of various preoperative
      clinical variables 100 patients with aortic valve replacement were matched to the
      100 patients with replacement of the aortic root. The duration of follow-up for
      both groups was similar with 37 + 17 months (range, 9 to 70) for the CarboSeal
      group and 38 + 14 months (range, 13 to 65) for the CarboMedics group. Survival
      and morbidity were calculated by Kaplan-Meier analysis and risk-adjusted
      mortality was evaluated by multivariate analysis in a Cox regression model.
      RESULTS: The early postoperative mortality of 1% in the CarboSeal group and 4% in
      the CarboMedics group was insignificantly different. Although the overall
      survival rate at 5 years was lower (60.7% vs 86.3%; p = 0.13) in the CarboSeal
      group, the freedom from cardiac mortality and valve-related morbidity was similar
      in the two groups. CONCLUSIONS: Replacement of the ascending aorta and aortic
      valve can be performed with similar operative risk, valve-related morbidity, and
      late cardiac mortality as isolated aortic valve replacement.

PMID- 11465205
TI  - Self-inflicted pneumothoraces.
AB  - Self-inflicted pneumothoraces are rare manifestations of psychiatric illness. Two
      patients with self-inflicted pneumothoraces are reported, and the typical
      clinical features of factitious disorders are described. If thoracic surgeons are
      aware of these conditions, inappropriate surgery- and poor outcomes-can be
      avoided.

PMID- 11465206
TI  - Thoracic left kidney: a differential diagnostic dilemma for thoracic surgeons.
AB  - We report a case of left thoracic kidney that was identified after a detailed
      workup for a left thoracic mass that appeared on a routine chest roentgenogram of
      a young adult. Intravenous pyelography and angiography clearly identified this
      rare anomaly. Anatomical features and clinical implications of this condition are
      presented.

PMID- 11465207
TI  - Angiomatoid fibrous histiocytoma in mediastinum.
AB  - Angiomatoid fibrous histiocytoma (AFH) is a rare tumor of soft tissue with low
      grade malignancy that occurs most commonly in the soft tissues of the extremities
      or trunk. We present a case of AFH of the mediastinum, which is a very unusual
      site for this tumor. The patient has survived with no recurrence of the disease
      for 60 months after surgery and adjuvant radiotherapy.

PMID- 11465208
TI  - Primitive neuroectodermal tumor of the pulmonary hilum in an adult.
AB  - A rare case of a thoracic primitive neuroectodermal tumor in an adult is
      presented. In this case, the aggressive, rapid progression characteristic of the
      disease was evident.

PMID- 11465209
TI  - Multiple ball thrombi in the right atrium: a game of billiards.

PMID- 11465210
TI  - Substernal thoracoscopic guidance during sternal reentry.
AB  - Reentry sternotomy is commonplace, as more patients are returning for second,
      third, or more repeat cardiac procedures. Catastrophic hemorrhage remains the
      most dreaded complication during reentry and carries a significant morbidity and
      mortality. Although various methods are used to reduce the risk of hemorrhage, we
      have found that substernal thoracoscopy is preferable. Our experience with this
      technique in both adults and children is presented.

PMID- 11465211
TI  - Minimally invasive harvesting of the radial artery as a coronary artery bypass
      graft.
AB  - We harvested radial arteries for coronary artery bypass procedures with a
      minimally invasive technique for 40 patients through two transverse 2-cm
      incisions in the forearm. With the help of instruments developed by us, the
      operation can be performed either with the use of an endoscope or with the naked
      eye. There were no complications in the forearm or the hand. The condition of the
      intima of the arterial grafts was checked by transmission and scanning electron
      microscopic methods and was found to be intact.

PMID- 11465212
TI  - Aortopexy reduces anastomosis stress after repair of coarctation.
AB  - Restenosis after repair of coarctation with hypoplastic distal aortic arch is an
      important complication. Complete removal of ductal tissue, resection of isthmus
      area, and side-to-side arterioplasty of the distal aortic arch leads to a wide
      distance between the aortic arch and descending aorta; therefore, the anastomosis
      may remain under tension, increasing risk of restenosis. To reduce the tension,
      aortopexy of the descending aorta was used. The operative technique and the
      results in 16 neonates and infants are presented.

PMID- 11465213
TI  - Bronchoscopic dye injection for localization of small pulmonary nodules in
      thoracoscopic surgery.
AB  - A new method of marking small pulmonary nodules situated deep within the visceral
      pleura using a transbronchial approach has been developed. Once the tip of the
      sheath catheter has passed the tumor and reached the visceral pleura, as
      confirmed by computed tomography fluoroscopy, indigo carmine is injected through
      a bronchoscope into the lung parenchyma just beneath the visceral pleura. No
      complications related to the procedure were experienced. The dye-marking
      procedure enabled the nodules to be precisely located. This technique can provide
      appropriate guidance when used in conjunction with video-assisted thoracic
      operations.

PMID- 11465214
TI  - Skeletonization of the radial artery: advantages over the pedicled technique.
AB  - The radial artery is usually harvested as a pedicle with surrounding veins,
      perivascular fat, and areolar tissue. We describe an alternative technique of
      skeletonization of the radial artery and its potential advantages over the
      pedicled technique.

PMID- 11465215
TI  - Ethical and legal concerns in relationships with cardiologists.

PMID- 11465216
TI  - The human factor in cardiac surgery: errors and near misses in a high technology
      medical domain.
AB  - In this review, we discuss human factors research in cardiac surgery and other
      medical domains. We describe a systems approach to understanding human factors in
      cardiac surgery and summarize the lessons that have been learned about critical
      incident and near-miss reporting in other high technology industries that are
      pertinent to this field.

PMID- 11465217
TI  - Transthoracic versus transhiatal resection for carcinoma of the esophagus: a meta
      analysis.
AB  - There is much controversy about the surgical approach to esophageal carcinoma:
      should an extensive resection be done to optimize long-term survival or should
      the extent of the operation be limited to obtain lower perioperative morbidity
      and mortality rates? We systematically reviewed the English-language literature
      published during the past decade, with emphasis on the differences between
      transthoracic and transhiatal resections regarding early morbidity, in-hospital
      mortality rates, and 3- and 5-year survival. Although transthoracic resections
      had significantly higher early (pulmonary) morbidity and mortality rates, 5-year
      survival was approximately 20% after both transthoracic and transhiatal
      resections.

PMID- 11465218
TI  - As originally published in 1994: Changes in patients undergoing coronary artery
      bypass grafting: 1987-1990. Updated in 2000. Northern New England Cardiovascular
      Disease Study Group.

PMID- 11465219
TI  - Classification of pulmonary atresia with ventricular septal defect.

PMID- 11465220
TI  - The pride of our surgical heritage.

PMID- 11465221
TI  - Sparing of the native right ventricle for heart transplantation.

PMID- 11465222
TI  - Saphenectomy wound complications: fact or fiction.

PMID- 11465223
TI  - Heparin and platelet function.

PMID- 11465224
TI  - Bronchovascular sleeve resection for lung cancer.

PMID- 11465225
TI  - Pulmonary function and prognosis: VATS versus thoracotomy.

PMID- 11465226
TI  - Hemodynamic performance of stented and stentless aortic bioprostheses.
AB  - BACKGROUND: This study compares the hemodynamic performance of stented and
      stentless bioprostheses used for aortic valve replacement in patients with aortic
      stenosis and small aortic root. METHODS: Between 1995 and 1998, 37 patients with
      a 21-mm aortic annulus (group 1) underwent aortic valve replacement with either a
      21-mm Edwards Perimount or a 23-mm St. Jude Toronto bioprosthesis whereas 47
      patients with a 23-mm aortic annulus (group 2) received either a 23-mm Medtronic
      Mosaic or a 25-mm Edwards Prima bioprosthesis. In each group mean and peak
      gradients, effective orifice area index, and left ventricular mass index were
      compared during follow-up. RESULTS: Group 1 patients showed a significant
      reduction of mean (p < 0.001) and peak gradients (p = 0.001) during follow-up,
      more evident for St. Jude Toronto versus Edwards Perimount (p = 0.02 and p =
      0.05, respectively). Group 2 patients showed a significant reduction of mean and
      peak gradients (p < 0.001), more evident for Edwards Prima versus Medtronic
      Mosaic (p < 0.001 and p = 0.07, respectively). Effective orifice area index
      significantly increased only in group 1 (p = 0.005). Left ventricular mass index
      significantly decreased in all patients regardless of the type of valve (p <
      0.001). Patients with Edwards Prima showed a trend to a higher regression of left
      ventricular mass index versus Medtronic Mosaic recipients (p = 0.07).
      CONCLUSIONS: After aortic valve replacement, stented and stentless bioprostheses
      exhibited similar results with a more evident hemodynamic improvement during
      follow-up in the stentless valves. Stented bioprostheses of new generation,
      however, may parallel the hemodynamic performance of stentless valves and appear
      to be a valid alternative for aortic valve replacement in elderly patients with a
      small aortic annulus.

PMID- 11465227
TI  - Recurrent infective endocarditis: a multivariate analysis of 21 years of
      experience. arenzul@tin.it.
AB  - BACKGROUND: To evaluate which variables predict recurrence of endocarditis after
      surgical treatment, we reviewed our 21-year experience. METHODS: Between January
      1979 and May 2000, 308 consecutive valve replacement procedures for infective
      endocarditis were performed in 271 patients. Univariate and multivariate time
      related analyses were performed to retrospectively evaluate the role of the
      following variables in the development of recurrent postoperative endocarditis:
      gender, site of endocarditis, previous valve disease, drug abuse, diabetes,
      positive valve/blood cultures, sepsis, perivalvular involvement, previous embolic
      events, type of replacement device, and persistent postoperative fever. RESULTS:
      Clinical and echocardiographic follow-up was 97.36% complete, mean follow-up time
      was 53.2+/-3.4 months. Recurrent endocarditis developed in 58 cases (22.5%).
      Variables predicting recurrence were prosthetic endocarditis (p = 0.00001),
      positive valve culture (p = 0.0039), and persistence of fever at the seventh
      postoperative day (p = 0.000001). CONCLUSIONS: Correct protocols of antibiotic
      therapy guided by microbiology may reduce the incidence of recurrent endocarditis
      to allow for surgery on sterile tissues and to prevent prosthetic infection.
      Recurrence rate is not affected by the choice of valve substitute, but can be
      prevented by complete surgical debridement.

PMID- 11465228
TI  - International normalized ratio self-management after mechanical heart valve
      replacement: is an early start advantageous?
AB  - BACKGROUND: Severe thromboembolic and hemorrhagic complications after mechanical
      heart valve replacement essentially depend on the intensity of oral
      anticoagulation and the fluctuation of individual international normalized ratio
      (INR) values. METHODS: After heart valve replacement with Medtronic Hall, St.
      Jude Medical, and CarboMedics implants, patients were randomly divided into two
      groups, one controlling INR values at home, the other being monitored by family
      practitioners. RESULTS: Almost 80% of the INR values recorded by patients at home
      were within the stipulated therapeutic range, INR 2.5 to 4.5, compared with just
      62% of INR values recorded by family practitioners. The overall complication rate
      (hemorrhages and thromboembolic events) of the self-management group was
      significantly (p < 0.05) decreased compared with the conventional group.
      CONCLUSIONS: Through INR self-management, an improvement in the quality of
      ongoing oral anticoagulation could be shown. Starting this form of therapeutic
      control early after mechanical heart valve replacement appears to effect a
      further reduction in anticoagulant-induced complications.

PMID- 11465229
TI  - Hemodynamic performance of the 21-mm Sorin Bicarbon mechanical aortic prostheses
      using dobutamine Doppler echocardiography.
AB  - BACKGROUND: Small-sized mechanical aortic prostheses are commonly associated with
      generation of high transvalvular gradients, particularly in patients with large
      body surface area, and can result in patient-prosthesis mismatch. This study
      evaluates the hemodynamic performance of 21-mm Sorin Bicarbon bileaflet
      mechanical prostheses using dobutamine stress echocardiography. METHODS: Fourteen
      patients (7 women; mean age, 63+/-8 years) who had undergone aortic valve
      replacement with a 21-mm Sorin Bicarbon bileaflet mechanical prosthesis 32.4+/
      5.1 months previously were studied. After a resting Doppler echocardiogram, a
      dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and
      increased to 30 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed- and
      continuous-wave Doppler echocardiographic studies were performed at rest and at
      the end of each increment of dobutamine. Both peak and mean velocity and pressure
      gradient across the prostheses were measured, and effective orifice area,
      discharge coefficient, and performance index were calculated. RESULTS: Dobutamine
      stress increased heart rate and cardiac output by 83% and 81%, respectively (both
      p < 0.0001), and mean transvalvular gradient increased from 15.6+/-5.5 mm Hg at
      rest to 35.4+/-11.9 mm Hg at maximum stress (p < 0.0001). Although the indexed
      effective orifice area was significantly lower in patients with a larger body
      surface area, this was not associated with any significant pressure gradient. The
      performance index of this valve was unchanged throughout the study. Regression
      analyses demonstrated that the mean transvalvular gradient at maximum stress was
      independent of all variables except resting gradient (p = 0.05). Body surface
      area had no association with the changes in cardiac output, transvalvular
      gradient at maximum stress, and effective orifice area. CONCLUSIONS: These data
      show that the 21-mm Sorin Bicarbon bileaflet mechanical prosthesis offers an
      excellent hemodynamic performance with full utilization of its available orifice
      when implanted in the aortic position. The lack of significant transvalvular
      gradient in patients with a larger body surface area suggests that patient
      prosthesis mismatch is highly unlikely when this prosthesis is used.

PMID- 11465230
TI  - Preoperative intraaortic balloon pumps in high-risk patients undergoing open
      heart surgery.
AB  - BACKGROUND: The use of the preoperative intraaortic balloon pump (IABP) in
      patients with severe left ventricular dysfunction or unstable angina with
      critical coronary anatomy is becoming more frequent as surgical casemix changes.
      The aim of this study was to determine the impact of preoperative IABP use on
      survival in high-risk patients having open heart surgery. METHODS: Prospectively
      collected data for 645 consecutive patients were reviewed. Patients receiving an
      IABP were identified and grouped as follows: group A (preoperative IABP for high
      risk nonemergent cases), group B (preoperative IABP for emergent cases), and
      group C (intra/postoperative IABP). Risk-adjusted hospital mortality rates in
      these three groups was compared using the modified Parsonnet score for
      preoperative risk stratification. RESULTS: IABPs were used in 101 cases (16%).
      The predicted versus actual hospital mortality rate was 20% versus 5.7% in group
      A, 32.1% versus 47.6% in group B, and 12.6% versus 22.2% in group C (group A vs
      group B, p = 0.0014; group A vs group C, p = 0.012). IABP-related morbidity
      occurred in 3% of cases (all in group C). CONCLUSIONS: Risk-adjusted mortality
      was significantly lower in high-risk cases with preoperative IABPs compared with
      emergent cases and intraoperative/postoperative IABPs. We encourage the use of
      preoperative IABPs in selected high-risk patients.

PMID- 11465231
TI  - Elevations in antidiuretic hormone and aldosterone as possible causes of fluid
      retention in the Maze procedure.
AB  - BACKGROUND: Reduced levels of atrial natriuretic peptide (ANP) has been suggested
      as a cause of fluid retention after combined Maze and valvular surgery. This
      study aimed to assess hormonal activation in the perioperative setting of
      isolated Maze procedures. METHODS: Changes in ANP, brain natriuretic peptide
      (BNP), antidiuretic hormone (ADH), aldosterone, and angiotensin II were measured
      in 16 patients (mean age 53+/-9 years) without concomitant heart disease
      undergoing the Maze (III) procedure. Ten matched patients (mean age 56+/-9 years)
      undergoing multivessel coronary artery bypass grafting served as controls.
      Measurements with hemodynamic correlates were obtained at baseline and after
      ventricular pacing (100 stimulations/minute), directly preoperatively,
      postoperatively and the first postoperative day. Weight gain and diuretic
      requirements were recorded. RESULTS: The major differences in hormonal response
      were significantly higher plasma levels of ADH (Maze preoperative 1.1+/-0.4,
      postoperative 24.9+/-16.7 pmol/L; controls preoperative 1.1+/-0.1, postoperative
      3.7+/-3.5 pmol/L) and aldosterone (Maze preoperative 106+/-94, postoperative
      678+/-343 pmol/L; controls preoperative 124+/-79, postoperative 171+/-93 pmol/L)
      in the Maze group on the first postoperative day (p < 0.001). Preoperative
      baseline plasma levels of ANP and pulmonary capillary wedge pressures (PCWP) were
      higher in the Maze group but this difference was abolished by pacing, and
      postoperatively, ANP levels changed in parallel to the PCWP in both groups.
      Diuretic requirements were significantly higher in the Maze group. CONCLUSIONS:
      Substantial increases in ADH and aldosterone were observed after the Maze
      procedure, indicating these hormones as important determinants in postoperative
      fluid retention. The role for ANP in this setting may be a less prominent than
      previously reported.

PMID- 11465232
TI  - The question of racial bias in thoracic surgery: appearances and realities.

PMID- 11465233
TI  - Thoracic epidural anesthesia does not influence the occurrence of postoperative
      sustained atrial fibrillation.
AB  - BACKGROUND: To evaluate whether thoracic epidural anesthesia (TEA) can reduce the
      incidence of atrial fibrillation (AF) after coronary artery bypass grafting
      (CABG). METHODS: Forty-one patients undergoing CABG were treated with TEA
      intraoperatively and postoperatively. Another 80 patients served as the control
      group. The sympathetic and parasympathetic activities were evaluated by analysis
      of neuropeptides, catecholamines and heart rate variability (HRV), preoperatively
      and postoperatively. RESULTS: Postoperative AF occurred in 31.7% of the TEA
      treated patients and in 36.3% of the untreated patients (p = 0.77). TEA
      significantly suppressed sympathetic activity, as indicated by a less pronounced
      increase of norepinephrine and epinephrine (p = 0.03, p = 0.02) and a significant
      decrease of neuropeptide Y (p = 0.01) postoperatively in TEA-treated patients
      compared to untreated patients. The HRV variable expressing sympathetic activity
      was significantly lower and the postoperative increase in heart rate was
      significantly less in the TEA group than in the control group after surgery (p =
      0.01, p < 0.001). Among patients developing AF, the maximal number of
      supraventricular premature beats per minute increased significantly in untreated
      patients postoperatively but remained unchanged in TEA-treated patients (p =
      0.004 versus p = 0.86). CONCLUSIONS: TEA has no effect on the incidence of
      postoperative sustained AF, despite a significant reduction in sympathetic
      activity.

PMID- 11465234
TI  - Prospective comparative study of brain protection in total aortic arch
      replacement: deep hypothermic circulatory arrest with retrograde cerebral
      perfusion or selective antegrade cerebral perfusion.
AB  - BACKGROUND: The purpose of this study was to compare the results of total aortic
      arch replacement using two different methods of brain protection, particularly
      with respect to neurologic outcome. METHODS: From June 1997, 60 consecutive
      patients who underwent total arch replacement through a midsternotomy were
      alternately allocated to one of two methods of brain protection: deep hypothermic
      circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with
      selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and
      postoperative (3 weeks) brain CT scan, neurological examination, and cognitive
      function tests were performed. Serum 100b protein was assayed before and after
      the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation.
      RESULTS: Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2
      in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in
      2 (6.6%) of the SCP group (p = 0.6). The incidence of transient brain dysfunction
      was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4,
      13.3%, p = 0.05). Except in patients with strokes, S-100b values showed no
      significant differences in the two groups (RCP: SCP, prebypass 0.01+/-0.04:
      0.05+/-0.16, postbypass 2.17+/-0.94: 1.97+/-1.00, 24 hours 0.61+/-0.36: 0.60+/
      0.37, 48 hours 0.36+/-0.45: 0.46+/-0.40 microg/L, p = 0.7). There were no
      intergroup differences in the scores of memory decline (RCP 0.74+/-0.99; SCP
      0.55+/-1.19, p = 0.6), orientation (RCP 1.11+/-1.29; SCP 0.50+/-0.76, p = 0.08),
      or intellectual function (RCP 1.21+/-1.27; SCP 1.05+/-1.15, p = 0.7).
      CONCLUSIONS: Both methods of brain protection for patients undergoing total arch
      replacement resulted in acceptable levels of mortality and morbidity. However,
      the prevalence of transient brain dysfunction was significantly higher in
      patients with the RCP.

PMID- 11465235
TI  - Prevention and detection of spinal cord injury during thoracic and
      thoracoabdominal aortic repairs.
AB  - BACKGROUND: Spinal cord injury is a most dreaded and unpredictable complication.
      In this study, based on our experimental results in dogs and early clinical
      results, we reviewed the incidence of paraplegia and the detection of spinal cord
      injury. METHODS: Eighty-two patients who underwent elective surgical repair of
      the descending thoracic and thoracoabdominal aorta over 17 years were subjects
      for this study. Sixty-two patients were male and 20 were female. Their mean age
      was 61.6 years (range, 17 to 81 years). Monitoring somatosensory evoked
      potentials (SEP) and measurement of mean distal aortic pressure and cerebrospinal
      fluid pressure were performed perioperatively. RESULTS: Sixty patients had no
      ischemic change in SEP. In 17 patients with significant ischemic changes of SEP,
      SEP recovered by increasing spinal cord perfusion pressure to more than 40 mm Hg.
      Two patients with complete loss of SEP experienced paraplegia. One patient had
      delayed paraplegia. CONCLUSIONS: These results strongly suggest that SEP, mean
      distal aortic pressure, cerebrospinal fluid pressure should be monitored during
      aortic cross-clamping. Maintaining spinal cord perfusion pressure at more than 40
      mm Hg by increasing mean distal aortic pressure or withdrawal of cerebrospinal
      fluid is valuable for preventing paraplegia.

PMID- 11465236
TI  - Application of "double bridge mechanical" resuscitation for profound cardiogenic
      shock leading to cardiac transplantation.
AB  - BACKGROUND: In patients with acute profound cardiogenic circulatory failure
      unresponsive to conventional resuscitation, we instituted immediate aggressive
      application of extracorporeal membrane oxygenation (ECMO) to restore circulatory
      stability. Long-term hemodynamic support was accomplished with an early "bridge"
      to ventricular assist device (VAD) before definitive treatment with cardiac
      transplantation. METHODS: A respective review of ECMO and VAD data registries was
      instituted. RESULTS: From May 1996 to July 2000, 23 patients were placed on ECMO
      support for profound cardiogenic circulatory failure. Eleven patients (47%) were
      withdrawn from support due to severe neurologic injury or multisystem organ
      failure. Three patients (13%) were weaned off ECMO with good outcome. Nine
      patients (39%) were transferred to a VAD. Two patients expired while on VAD
      support, and 7 of the VAD-supported patients (78%) survived to transplantation.
      Overall survival was 43%. CONCLUSIONS: Emergent ECMO support is a salvage
      approach for cardiac resuscitation once conventional measures have failed. In
      neurologically intact patients, the early transfer to a VAD quickly stabilizes
      hemodynamics, avoids complications, and is essential for long-term circulatory
      support before definitive treatment with cardiac transplantation.

PMID- 11465237
TI  - From art to science: a fairy tale? The future of academic surgery.

PMID- 11465238
TI  - Evaluation of predictors of clinical outcome after partial left ventriculectomy.
AB  - BACKGROUND: Outcome after partial left ventriculectomy (PLV) is difficult to
      predict. Our goal was to determine if clinical measurements including exercise
      testing could predict outcome after PLV. METHODS: Sixteen patients with dilated
      cardiomyopathy had left ventricular ejection fraction, left ventricular end
      diastolic diameter, amount of mitral regurgitation (MR), New York Heart
      Association (NYHA) functional class, and cardiopulmonary exercise testing
      measurements measured before PLV and 3 months after PLV. Eleven patients who
      remained stable after PLV (group 1) were compared with 5 patients who
      deteriorated after PLV (group 2). RESULTS: Similar significant improvements were
      seen in both groups 3 months post-PLV with respect to left ventricular ejection
      fraction (group 1: 0.136+/-0.037 to 0.212+/-0.046; group 2: 0.139+/-0.042 to
      0.179+/-0.073) and left ventricular end-diastolic diameter (group 1: 8.5+/-0.7 to
      7.0+/-0.6 cm; group 2: 7.6+/-0.6 to 6.5+/-0.6 cm). The MR grade (1.0+/-0.6 versus
      2.5+/-0.6), NYHA functional class (1.5+/-0.31 versus 2.5+/-0.6), and peak oxygen
      consumption (17.8+/-1.1 versus 12.2+/-2.0) were significantly different in the
      two groups 3 months after PLV (p < 0.05, analysis of variance). CONCLUSIONS:
      Patients that do not show significant improvement in peak oxygen consumption,
      NYHA class and significant decrease in the amount of MR 3 months after PLV,
      compared with pre-PLV, are at increased risk of clinically deteriorating.

PMID- 11465239
TI  - Relapsing bacteremia in patients with ventricular assist device: an emergent
      complication of extended circulatory support.
AB  - BACKGROUND: Ventricular assist devices (VAD) are currently approved for use as a
      bridge for transplantation. Although reports have suggested acceptable rates of
      survival of patients with VAD, there is little information regarding the
      mechanism and etiology of bacteremia in these patients. METHODS: We prospectively
      followed patients who underwent VAD implantation and developed bacteremia during
      VAD support at the University of Pittsburgh Medical Center. Relapsing bacteremia
      was defined as at least two episodes of positive blood cultures with a
      genetically related organism on 2 different days. Species identification and
      susceptibility testing were performed on all isolates. Pulse field gel
      electrophoresis was performed on selected blood and VAD isolates. RESULTS:
      Between January 1998 and August 1999, 3 patients with VAD developed relapsing
      bacteremia, which was treated with full courses of antibiotic agents, 2 of whom
      also developed VAD endocarditis. All 3 patients had documented driveline or
      device pocket infections with these isolates. Consecutive blood and VAD isolates
      were found to be genetically related within each patient. CONCLUSIONS: These
      patients with bacteremia after VAD implantation had relapse due to the same
      strain, which may have originated from indolent driveline infection. Endovascular
      infection in this setting is difficult to eradicate with antibiotic agents and
      carries a high mortality. These patients should be considered to have priority
      for orthotopic heart transplantation.

PMID- 11465240
TI  - Gene therapy to control hypertension: current studies and future perspectives.
AB  - Hypertension is a complex pathophysiological state that leads to serious
      complications, including heart failure, coronary artery disease, and abnormal
      renal function. While traditional therapies can be effective in controlling the
      effects of hypertension, they offer no long-term cure and often lead to patient
      noncompliance, thereby diminishing their effectiveness. These reasons, coupled
      with the recent developments in gene transfer and somatic cell gene delivery, led
      researchers to explore alternative options that can produce long-term control of
      hypertension. Gene therapy offers the potential to yield lasting antihypertensive
      effects by influencing the genes associated with hypertension. In this review, we
      will discuss the merits of sense versus antisense strategies in controlling
      hypertension. We also discuss the advantages and disadvantages of both viral and
      nonviral vector types for the systemic delivery of genes for hypertension
      research. Results of our research group on the retrovirus-mediated delivery of
      the angiotensin type I receptor-antisense on the prevention of hypertension and
      related cardiovascular pathophysiology will be summarized. Finally, we discuss
      the future of this gene therapy approach in the reversal and long-term control of
      hypertension.

PMID- 11465241
TI  - Risk factors for kidney stones in older women in the southern United States.
AB  - BACKGROUND: The occurrence of kidney stones is disproportionate in the southern
      region of the United States. Risk factors for the occurrence of kidney stones in
      this geographic area have not been reported previously. METHODS: The Women's
      Health Initiative (WHI) is an ongoing multicenter clinical investigation of
      strategies for the prevention of common causes of morbidity and mortality among
      postmenopausal women. A case-control ancillary study was conducted on 27,410
      (white or black) women enrolled in the 9 southern WHI clinical centers. There
      were 1,179 cases (4.3%) of kidney stones at the baseline evaluation. Risk factors
      for stone formation were assessed in cases versus age- and race-matched control
      subjects. RESULTS: Risk factors (univariate) included low dietary potassium
      (2,404 versus 2,500 mg/day, P = 0.006), magnesium (243 versus 253 mg/day, P =
      0.003) and oxalate (330 versus 345 mg/day, P = 0.02) intake, as well as increased
      body mass index (28.5 versus 27.7 kg/m2, P = 0.001) and a history of hypertension
      (42% versus 34%, P = 0.001). A slightly lower dietary calcium intake (683 versus
      711 mg/day, P = 0.04) was noted in case subjects versus control subjects, but
      interpretation was confounded by the study of prevalent rather than incident
      cases. Supplemental calcium intake >500 mg/day was inversely associated with
      stone occurrence. CONCLUSION: Multivariate risk factors for the occurrence of
      kidney stones in postmenopausal women include a history of hypertension, a low
      dietary intake of magnesium, and low use of calcium supplements.

PMID- 11465242
TI  - Overweight/obesity, smoking, and heavy alcohol consumption are important
      determinants of plasma PAI-1 levels in healthy men.
AB  - BACKGROUND: Plasma plasminogen activator inhibitor-1 (PAI-1) is thought to
      contribute to the pathogenesis of atherosclerosis and is a predictor of ischemic
      heart disease. METHODS: We investigated the effects of overweight/obesity and
      lifestyle (smoking and alcohol intake) on plasma PAI-1 levels in 203 healthy men
      (age 44.5+/-8.1) who visited our department for health check. Information on
      alcohol intake and smoking habit was obtained by a questionnaire. RESULTS: Plasma
      PAI-1 was significantly correlated to plasma leptin, body mass index (BMI),
      percent body fat, plasma levels of triglyceride, and gamma-glutamyl
      transpeptidase. Plasma PAI-1 was also increased significantly in smokers and in
      heavy drinkers. Plasma PAI-1 levels increased in an additive manner by the
      combination of risk factors (BMI > or =25 kg/m2, smoking, and heavy alcohol
      consumption). Nonobese, nonsmoking, nondrinkers showed the lowest plasma PAI-1
      levels, whereas overweight/obese, smoking, heavy drinkers showed the highest
      levels (11.2+/-2.2 ng/mL versus. 34.0+/-4.3 ng/mL, P < 0.0001). CONCLUSIONS:
      These results suggest that overweight/obesity and unfavorable lifestyle such as
      smoking and heavy alcohol consumption may increase plasma PAI-1 levels and might
      be linked to the risk of ischemic heart disease.

PMID- 11465243
TI  - Spontaneous baroreflex sensitivity and heart rate variability are not superior to
      classic autonomic testing in older patients with type 2 diabetes.
AB  - BACKGROUND: Early detection of cardiac autonomic neuropathy (CAN) permits
      individual risk stratification. Spontaneous heart rate variability (HRV) and
      baroreflex sensitivity (BRS) are suggested to be superior to classic autonomic
      testing in that they detect CAN earlier, with greater reliability, and do not
      require the patient's undue attention. METHODS: To test that hypothesis, we
      studied 53 diabetic patients (mean age, 55 years) and 38 age-matched healthy
      control subjects (HC). Subjects underwent deep breathing, Valsalva maneuver, and
      orthostatic testing. Each abnormal test was counted as 1 point. A change in
      systolic blood pressure during standing of more than 10 mm Hg was graded with a
      single point; a decrease of more than 20 mm Hg received 2 points. A total score
      of zero was regarded as no CAN (noCAN), a score > or =4 as severe CAN (sCAN), and
      scores of 1 to 3 as mild CAN (mCAN). Spontaneous BRS was determined using the
      sequence technique. HRV was calculated as coefficient of variation (CV), high
      frequency power (HF) and low frequency power (LF). RESULTS: Mean group values for
      HRV and BRS were: CV = 3.9+/-1.3; 4.0+/-1.3; 2.4+/-1.1; and 1.2+/-0.4; BRS = 8+/
      3; 8+/-5; 5+/-2; and 2+/-2 msec/mm Hg for HC n = 38, noCAN n = 15, mCAN n = 26,
      and sCAN n = 12, respectively. BRS was similar in HC and patients with noCAN. In
      sCAN, BRS detected only 10 of 12 patients. HRV and BRS did not improve
      reclassification based on discriminant analysis. CONCLUSION: BRS and HRV did not
      detect CAN in older diabetic patients better than classic autonomic testing.

PMID- 11465244
TI  - Identifying and assisting the impaired physician.
AB  - An impaired physician is one unable to fulfill professional or personal
      responsibilities because of psychiatric illness, alcoholism, or drug dependency.
      Current estimates are that approximately 15% of physicians will be impaired at
      some point in their careers. Although physicians may not have higher rates of
      impairment compared with other professionals, factors in their background,
      personality, and training may contribute and predispose them to drug abuse and
      mental illness, particularly depression. Many physicians possess a strong drive
      for achievement, exceptional conscientiousness, and an ability to deny personal
      problems. These attributes are advantageous for "success" in medicine;
      ironically, however, they may also predispose to impairment. Identifying
      impairment is often difficult because the manifestations are varied and
      physicians will typically suppress and deny any suggestion of a problem.
      Identification is essential because patient well-being may be at stake, and
      untreated impairment may result in loss of license, health problems, and even
      death. Fortunately, once identified and treated, physicians often do better in
      recovery than others and typically can return to a productive career and a
      satisfying personal and family life.

PMID- 11465245
TI  - Syncope and arrhythmias: role of the electrophysiological study.

PMID- 11465246
TI  - Foreign body aspiration diagnosed by microscopy.
AB  - We report a rare case of foreign body aspiration diagnosed by microscopic
      analysis of a sample of the foreign body. A 50-year-old man presented with a 5
      month history of 40 pound weight loss and a nonresolving right lower lobe
      pneumonia. Medical history, radiographic studies, direct visualization of the
      foreign body by flexible fiberoptic bronchoscopy, and gross examination of a
      sample of the foreign body retrieved by a forceps biopsy catheter failed to yield
      the diagnosis. Moderate bleeding associated with the bronchoscopic "biopsy"
      procedure contributed to a preliminary misdiagnosis of endobronchial tumor.
      Microscopic analysis of the "biopsy" specimen demonstrated vegetable matter. The
      patient underwent rigid bronchoscopy and a peanut was retrieved from the bronchus
      intermedius. He was maintained on antibiotics for an additional 8 weeks and had
      complete clinical and radiographic recovery. The epidemiology, presentation, and
      management strategies of foreign body aspiration in the adult are briefly
      reviewed.

PMID- 11465247
TI  - Doxylamine overdose as a potential cause of rhabdomyolysis.
AB  - Doxylamine succinate, an over-the-counter antihistamine, is commonly used as a
      nighttime sleep aid in the short-term management of insomnia. It is also used in
      combination with antitussive and decongestant agents for the temporary relief of
      common cold symptoms. Doxylamine is frequently involved in accidental and
      intentional overdoses. Rhabdomyolysis and secondary acute renal failure are rare
      but potentially serious complications, making early recognition and treatment
      essential. With the large number of nonprescription antihistamines and sleep aids
      available to the general public, it is important to keep in mind that overdose is
      a potential problem. The complications associated with overdose of these
      medications are just as life threatening as those associated with prescription
      drugs. A high index of suspicion and evaluation of rhabdomyolysis is warranted in
      antihistamine toxicity. We report an observation of severe rhabdomyolysis
      associated with doxylamine overdose.

PMID- 11465248
TI  - Potential therapeutic effect of simvastatin on progressive renal failure and
      nephrotic-range proteinuria caused by renal cholesterol embolism.
AB  - We report our experience with a 62-year-old Japanese man with cholesterol crystal
      embolism after angiographic procedures performed because of intermittent
      claudication. In addition to progressive renal failure and nephrotic-range
      proteinuria, cutaneous ischemia, consisting of livedo reticularis in the lower
      limbs and digital necrosis at the tip of the right toe, and fundoscopic findings
      showing several white spots in the branches of retinal artery were also observed.
      Progressive renal failure and nephrotic-range proteinuria were halted just after
      treatment with simvastatin. Thus, simvastatin can exert a beneficial therapeutic
      effect on renal cholesterol embolism.

PMID- 11465249
TI  - Cholesterol embolism causing delayed healing of a foot ulcer.
AB  - A cholesterol embolism presents with various systemic and local manifestations
      giving rise to a diagnostic dilemma. We report a case of cholesterol embolism of
      the leg that delayed the healing of a foot ulcer, necessitating a toe amputation.
      This report points to the potential of cholesterol emboli to cause a significant
      compromise in the vascular supply.

PMID- 11465250
TI  - Small artery remodeling in hypertension: can it be corrected?
AB  - Vascular structure, function, and mechanics are altered in hypertension, which
      contributes to an important degree to complications of elevated blood pressure.
      Vascular hypertrophy with collagen deposition and increased stiffness is found in
      large arteries, whereas in small arteries, smooth muscle cells are restructured
      around a smaller lumen, and there is no net growth of the vascular wall,
      particularly in milder forms of hypertension. Hypertrophic remodeling and
      increased small artery stiffness may be found in more severe hypertension.
      Endothelial dysfunction occurs in large or smaller vessels in a variable
      percentage of patients, particularly in presence of other risk factors such as
      diabetes, smoking, dyslipidemia, and advanced atherosclerosis. In clinical
      trials, 1-year treatment with angiotensin-converting enzyme inhibitors,
      angiotensin AT1 receptor antagonists, and long-acting calcium channel blockers
      corrected small artery structure and endothelial dysfunction in hypertensive
      patients, whereas beta-adrenergic receptor blockers did not. Improved outcomes in
      hypertensive patients demonstrated in recent trials with some but not others of
      these agents could be a consequence, at least in part, of vascular protection
      offered by some antihypertensive agents.

PMID- 11465251
TI  - The Eurocleft project 1996-2000: overview.
AB  - INTRODUCTION: The original Eurocleft project, a European intercentre comparison
      study, revealed dramatic differences in outcome, which were a powerful stimulus
      for improvement in the services of respective teams. The study developed a
      preliminary methodology to compare practices and the potential for wider European
      collaboration including opportunities for the promotion of clinical trials and
      intercentre comparison was recognized by the European Commission. Therefore, the
      project: 'Standards of Care for Cleft Lip and Palate in Europe: Eurocleft' ran
      between 1996 and 2000 and aimed to promote a broad uplift in the quality of care
      and research in the area of cleft lip and palate. RESULTS: The results of the
      1996-2000 project include: a register of services in Europe, with details of
      professionals and teams involved in cleft care, service organization, clinical
      protocols and special facilities for research; a set of common Policy Statements
      governing clinical practice for European cleft teams, Practice Guidelines
      describing minimum recommendations for care that all European children with
      clefts should be entitled to and recommendations for Documentation governing
      minimum records that cleft teams should maintain; encouraging initial efforts to
      compare outcomes (results) of care between centres. A survey showed a wide
      diversity in models of care and national policies as well as clinical practices
      in Europe. Of the 201 centres that registered with the network, the survey showed
      194 different protocols being followed for only unilateral clefts. CONCLUSION:
      Cleft services, treatment and research have undoubtedly suffered from haphazard
      development across Europe. Attainment of even minimum standards of care remains a
      major challenge in some communities and both the will to reform and a basic
      strategy to follow are overdue. It is hoped that the Eurocleft Consensus
      Recommendations reached during the present project will assist in improving the
      opportunities for tomorrow's patients. It is also hoped that the collaborative
      research now beginning under the European Commission's Framework V Programme will
      provide a focus for European researchers wishing to improve understanding,
      treatment and prevention of clefts of the lip, alveolus and palate in the years
      ahead.

PMID- 11465252
TI  - Levatorplasty, a new technique to treat hypernasality: anatomical investigations
      and preliminary clinical results.
AB  - BACKGROUND: Velopharyngoplasty is the most commonly used operative technique for
      the treatment of velopharyngeal insufficiency. By attaching a posterior
      pharyngeal flap to the velum, a nonphysiological situation is created in the
      upper airway. PURPOSE: The aim of this investigation was to find a new surgical
      approach to physiological reconstruction of the velopharyngeal sphincter.
      MATERIAL: Anatomical investigations were performed in four cadavers. From this
      study a new surgical technique was developed and called 'levatorplasty': the
      musculus longus capitis was taken to create a new muscular loop leading to (a) an
      augmentation of the posterior wall, (b) a medial shift of the lateral pharyngeal
      wall; and (c) stretching of the velum posteriorly. Thus, the velopharyngeal space
      was reduced and a physiological closure of the nasal airway space could be
      obtained. STUDY DESIGN: The levatorplasty was employed in nine cleft palate
      patients with velopharyngeal insufficiency. Pre- and postoperatively the
      velopharyngeal closure was evaluated by phonetic and radiological examination.
      RESULTS: The operation was easily performed without major complications. A
      concentric constriction with decrease of the velopharyngeal space was achieved
      and a definitive decrease of nasalance and hypernasality resulted. CONCLUSION:
      Long-term follow-ups have to verify whether these results will be stable. They
      also have to be compared with functional improvements following
      velopharyngoplasty or pharyngoplasty. Of special interest will be evaluation of
      the altered mobility of the lateral pharyngeal walls.

PMID- 11465253
TI  - Cyclopia: a radiological and anatomical craniofacial post mortem study.
AB  - Cyclopia is a rare foetal malformation characterized by a single palpebral
      fissure and a proboscis associated with severe brain malformation. Approximately
      1.05 in 100,000 births including stillbirths are identified as cyclopian.
      Cyclopia is not compatible with life. The authors present an anatomical and
      histological study of the fronto-orbito-maxillary region carried out after 3-D CT
      reconstruction in a 21 week-old foetus with cyclopia. Anatomical and histological
      observations suggest that the integrity of the trigeminal nerves is very
      important for the normal development of the embryological structures of the face.
      Fusion of the facial processes in the midline takes place even if central
      prosencephalic structures are absent. For this reason the face in cyclopia, in
      both its positive and negative aspects, constitutes a model for the study of the
      normal development of this region.

PMID- 11465254
TI  - Computer-aided 3-D simulation and prediction of craniofacial surgery: a new
      approach.
AB  - BACKGROUND: In plastic and reconstructive craniofacial surgery, careful
      preoperative planning is essential. In complex cases of craniofacial synostosis,
      rapid prototyping models are used to simulate the surgery and reduce operating
      time. Recently, 3-D CT model surgery has been introduced for presurgical planning
      and prediction of the postoperative result. OBJECTIVE: For simulation of
      craniofacial surgery a computer-based system was developed that allows
      visualization and manipulation of CT-data using computer graphics techniques.
      Surgical procedures in all areas of the bony skull can be performed
      interactively. RESULTS: The case of a child with scaphocephalus is presented.
      Surgery is planned using the craniofacial surgery simulator described above.
      CONCLUSION: The computer-based interactive surgery simulation systems presented
      here allow precise visualization of craniofacial surgery. The accurate computer
      aided 3-D simulation of bone displacements is also the prerequisite for transfer
      of the simulated surgery using a navigation system for surgery. Thus the
      preoperatively planned procedure could be transferred directly to the operating
      table.

PMID- 11465255
TI  - The fronto-orbital osteotomy as plastic-reconstructive approach to the anterior
      and middle skull base.
AB  - INTRODUCTION: A combined extra-intracranial access for the operative exploration
      of tumours of the anterior and middle skull base is indicated when the tumour
      extends intracranially and simultaneously into the nasal cavity, the paranasal
      sinuses or the orbit. METHODS: Two standardized modifications of the fronto
      orbital osteotomy, the fronto-orbito-nasal and the fronto-orbito-zygomatic
      osteotomy, allow safe removal of skull base tumours in these locations. In
      extensive skull base tumours, a modified bilateral fronto-orbital-zygomatic
      osteotomy can be used. RESULTS: Between February 1993 and July 2000 skull base
      tumours in 111 patients were resected using the presented methods. The most
      frequent tumour type was meningioma in 29 cases. Complications were encountered
      in 13 cases (11.7%). CONCLUSION: The advantages over other approaches are good
      extra- and intracranial overview and minimal cerebral trauma. Additional
      transfacial incisions are not usually necessary. Exact repositioning of the
      fronto-orbital segments leads to optimal aesthetic results.

PMID- 11465256
TI  - Original sagittal split osteotomy revisited for mandibular distraction.
AB  - INTRODUCTION: A malformed mandible and an abnormally positioned mandibular
      foramen make it difficult to plan an ideal osteotomy line for mandibular
      distraction. In addition, there have been reports of such complications as
      nonunion, damage and stretch injury of the inferior alveolar nerve and tooth germ
      damage when conventional osteotomy or corticotomy are used for mandibular
      distraction. The authors utilized the original sagittal split ramus osteotomy for
      mandibular distraction. PATIENTS AND METHODS: Five patients (three unilateral
      hemifacial microsomia, one bilateral hemifacial microsomia, and one mandibular
      retrusion) were included in this study of distraction osteogenesis using the
      sagittal split ramus osteotomy. Extraoral distraction devices were applied to the
      first four patients. An intraoral device with mono-cortical screw fixation was
      used for the fifth patient. RESULT: In all five cases, the results of the
      distraction were satisfactory. Complications (as listed) of conventional
      osteotomy when used for distraction were avoided. Satisfactory results were
      achieved and these were also well maintained postoperatively (mean follow up: 36
      months). CONCLUSION: The authors believe that sagittal osteotomy for mandibular
      distraction osteogenesis makes it possible, to avoid injury to the inferior
      alveolar nerve during operation and stretching injury during distraction and to
      prevent tooth germ injury. It is also possible to diversify the osteotomy line
      for various force vectors to enlarge the bony contact surface area. Therefore, we
      suggest that sagittal split ramus osteotomy should be used as a preferred
      modification of osteotomy for mandibular distraction.

PMID- 11465257
TI  - A complication of submandibular intubation in a panfacial fracture patient.
AB  - We present the complication of a mucocele in the floor of the mouth caused by a
      submandibular intubation in a patient with a panfacial fracture.

PMID- 11465258
TI  - Depression, anxiety and quality of life among scheduled cosmetic surgery
      patients: multicentre prospective study.
AB  - OBJECTIVE: To measure cosmetic surgery patients' state of psychological
      vulnerability. METHOD: A multicentre prospective study was carried out in three
      hospital departments. One hundred and three patients scheduled for cosmetic
      surgery were examined using a structured interview and using three assessment
      scales: the MADRS (Montgomery and Asberg Depression Rating Scale), the SISST
      (Social Interaction Self Statement Test) and the EQ-5D (EuroQol) which measures
      quality of life. RESULTS: The MADRS index was higher than that of the control
      group (p<0.01) with 20% depressive patients. SISST: the social anxiety was
      greater than that of the control group (p<0.001). The EQ-5D visual analogue scale
      average was 77.39% indicating that there was no significant difference when
      compared with the control group, but the descriptive EQ-5D revealed an
      overrepresentation of the anxiety/depression category (p<0.01); 50% had already
      taken psychotropic treatment of which 27% were an antidepressant. CONCLUSION: The
      cosmetic surgery population presents a significant state of psychological
      vulnerability.

PMID- 11465259
TI  - Reasons for patients' discontent and litigation.
AB  - INTRODUCTION: Discontent and litigation among patients is a problem which
      increasingly preoccupies the medical profession. AIM: We aim to analyse the
      origin of discontent and litigation and to help avoiding these claims. MATERIAL:
      One hundred and seventy-eight medical expert opinions were evaluated, all made
      following examination of the complainant. METHODS: Depending on the results of
      the clinical examination and the study of the files it was determined whether
      there was either a case of malpractice or insufficient informed consent, or no
      fault at all in a legal sense. In addition the patient and the surgeon were
      questioned as to their point of view regarding the procedure and their
      communication and relationship before and after treatment. RESULTS: Frequent
      complaints were pain (either during treatment or afterwards), major swelling or
      bleeding, disturbances of trigeminal or facial nerve function, poor scar
      formation, loss of teeth or fixtures, faulty occlusion and discrepancies between
      the expected and the actual result of treatment. In 26 cases actual faults made
      during medical treatment were discovered. In 49 further cases, poor explanation
      of the proposed procedure was the reason for complaint. In the majority of
      remaining cases, neither faulty treatment nor insufficient information given to
      the patient lead to the complaint but the patient's expectations were
      unrealistically high. CONCLUSION: A considerable proportion of lawsuits originate
      from misunderstandings, and not treatment errors: The surgeons often concentrate
      on the legal requirements of informed consent and neglect to explain the
      practical consequences of the operation; the patients in turn tend not to ask
      about possible complications.

PMID- 11465260
TI  - Refinement of velopharyngoplasty in patients with cleft palate by covering the
      pharyngeal flap with nasal mucosa from the velum' by Stoll C, Hochmuth M, Meister
      P, Soost F. Journal of Cranio-Maxillofacial Surgery, Vol. 28; 171-175 (2000).

PMID- 11465261
TI  - DEFRA starts to define its role.

PMID- 11465262
TI  - Concentrations of ketones in milk in early lactation, and reproductive
      performance of dairy cows.
AB  - Samples of blood and milk were taken from clinically ketotic cows at 12-hour
      intervals before and after treatment The concentration of beta-hydroxybutyrate
      was determined in plasma and milk, and the concentration of acetone was
      determined in milk. Measurement of milk acetone had the optimal combination of
      sensitivity, specificity and positive predictive value to identify ketotic cows
      and was subsequently used in a comparison of the fertility of ketotic and normal
      cows. Two samples of milk were taken approximately two weeks apart, between 12
      and 60 days after calving, from 410 cows on three farms and the concentration of
      acetone in the milk was measured. Thirty cows with milk acetone concentrations of
      at least 0.4 mmol/litre were compared with paired control cows with milk acetone
      concentrations less than 0.3 mmol/litre. The ketotic cows had a significantly
      longer calving-to-conception interval and a significantly higher culling rate due
      to a failure to conceive (P<0.05).

PMID- 11465263
TI  - Effectiveness and kinetic behaviour of tilmicosin in the treatment of respiratory
      infections in sheep.
AB  - Nineteen sheep which were anorexic, pyrexic, coughing, dyspnoeic and had a nasal
      discharge and symptomatic thoracic sounds on auscultation, received a single
      subcutaneous dose of 10 mg/kg bodyweight of tilmicosin. The clinical signs were
      eliminated within four to six days. The kinetic profiles of the drug after a
      single subcutaneous injection were compared in five healthy sheep and five
      infected sheep. More of the drug was absorbed by the infected animals and its
      concentration remained higher for significantly longer. The drug was well
      tolerated and no local or systemic side effects were observed.

PMID- 11465264
TI  - Parasites from Indo-Pacific hump-backed dolphins (Sousa chinensis) and finless
      porpoises (Neophocaena phocaenoides) stranded in Hong Kong.
AB  - Between 1993 and 1998, 28 Indo-Pacific hump-backed dolphins (Sousa chinensis) and
      32 finless porpoises (Neophocaena phocoenoides) stranded in Hong Kong territorial
      waters were examined postmortem for parasites. The nematode Halocercus pingi was
      discovered in the lungs of one hump-backed dolphin and in 10 finless porpoises,
      typically within abscesses or granulomata, and they were frequently accompanied
      by a catarrhal exudate and lesions characteristic of pneumonia. Seven of the 10
      finless porpoises were calves with substantial lungworm infections, and three
      were neonates with visible fetal folds and umbilical remnants, suggesting that H
      pingi is transferred to the neonate before birth or during lactation. Electron
      micrographs of H pingi should allow the nematode to be identified by other
      researchers. An ectoparasitic stalked barnacle (Xenobalanus globicipitis) was
      recovered from a finless porpoise, the first time that this species of barnacle
      has been recorded in Hong Kong's territorial waters.

PMID- 11465265
TI  - Attaching and effacing lesions in the intestines of two calves associated with
      natural infection with Escherichia coli O26:H11.

PMID- 11465266
TI  - Systemic bioavailability of erythromycin in cattle when applied by footbath.

PMID- 11465267
TI  - Anthelmintic resistance and parasite control in commercial eel farms:
      consequences for producers.

PMID- 11465268
TI  - Plasma glucocorticoid concentrations after fentanyl-droperidol, ketamine-xylazine
      and ketamine-diazepam anaesthesia in New Zealand white rabbits.

PMID- 11465269
TI  - Surgical management of a third degree perineal laceration and eversion of the
      bladder in a mare.

PMID- 11465270
TI  - Fibrosarcoma of the pars incisiva of the mandible of a cow.

PMID- 11465271
TI  - Detection of mycoplasmas in the lungs of rabbits with respiratory disease.

PMID- 11465272
TI  - Arrangements for payment of TVIs.

PMID- 11465273
TI  - Oral lesions in sheep.

PMID- 11465274
TI  - Observations on FMD-infected sheep in Ireland.

PMID- 11465275
TI  - Oral medication of rabbits.

PMID- 11465276
TI  - Lack of effective rumen-degradable protein for milking cows.

PMID- 11465277
TI  - PCV-2 from emaciated pigs in Mexico.

PMID- 11465293
TI  - Fine alterations of distortion-product otoacoustic emissions after moderate
      acoustic overexposure in guinea pigs.
AB  - Guinea pigs were exposed to a pure tone at 6 kHz and 80 dB SPL for 30 minutes in
      order to induce mild reversible auditory fatigue over the 4 hours following
      exposure. Cochlear monitoring aimed to compare the shifts in round-window
      compound action potentials (CAP) thresholds to those of 2f1-f2 distortion-product
      otoacoustic emissions (DPOAE, frequency of stimuli f1 and f2). Both responses
      were evaluated every 1/10th octave between 6 and 12 kHz for CAP thresholds, and
      from 4 to about 14 kHz for DPOAEs in response to 50- and 70-dB SPL stimuli. The
      auditory fatigue turned out to be sufficiently mild that DPOAEs remained present,
      so that their microstructure could be followed up while the stimulus frequency
      ratio f2/f1 was swept from 1.06 to 1.30 (fixed f2) so as to derive DPOAE level
      profiles against f2/f1 and group latencies. CAP thresholds decreased by about 10
      dB above 7.2 kHz, whereas DPOAE amplitudes decreased at most f2 frequencies from
      6.6 kHz to 15.2 kHz, with the range of decrease being slightly narrower at higher
      stimulus intensities. While the mean DPOAE shift after 1 hour was around 5 dB
      irrespective of stimulus intensity, it tended to increase slightly after 2 hours
      despite stable CAP thresholds. DPOAE profiles against f2/f1 were slightly
      modified by the auditory fatigue, so that the maximum tended to be reached at
      lower ratio. No significant variation of DPOAE latencies was found after acoustic
      overstimulation. These experiments show that complex DPOAE changes were induced
      by auditory fatigue and their relationship to CAP threshold changes does not seem
      to be straight-forward. Nonetheless, fine DPOAE recordings might be useful to
      detect early changes in cochlear mechanics.

PMID- 11465294
TI  - Brazilian Portuguese speech material and its application in occupational
      audiology.
AB  - Brazilian Portuguese speech test material consisting of nine monosyllabic 25-word
      lists was developed and digitally recorded on one channel of a compact disk with
      a speech-weighted modulated broadband noise on the other channel. Speech
      recognition functions in quiet and in noise, with word and phoneme scores, were
      obtained, and normative speech recognition data were standardized by
      determination of the psychometric function in 21 normally-hearing volunteers in
      quiet, and in 30 normally-hearing subjects in noise. The homogeneity of the nine
      lists was investigated in phoneme recognition data with 30 normally-hearing
      subjects. Speech recognition functions in quiet and in noise, with word and
      phoneme scores, were obtained in 65 noise-exposed workers. These results were
      very close to normative data, when tested in quiet, but significantly worse when
      tested in noise. It is concluded that the speech test material can be useful for
      estimating the communication performance of noise-exposed workers.

PMID- 11465295
TI  - Psychiatric disorders in tinnitus patients without severe hearing impairment: 24
      month follow-up of patients at an audiological clinic.
AB  - The relationship between tinnitus and psychiatric disorders has long been
      recognised. We have addressed this question by investigating the prevalence of
      psychiatric diagnosis in a consecutive series of tinnitus patients (n=82) without
      severe socially disabling hearing loss referred to an audiological clinic. The
      psychiatric evaluation was based on a standardised diagnostic interview (SCID-P)
      in accordance with the Diagnostic and Statistical Manual of mental disorders (DSM
      III-R) and on the Hospital Anxiety and Depression Scale (HAD Scale). An
      experienced psychiatrist performed the interview 24 months after the patient's
      first visit to the clinic. Lifetime depressive and anxiety disorders were
      recorded in 62 per cent and 45 per cent of the cases respectively, but only 34
      per cent had had contact with any healthcare institution for emotional
      disturbances. Only 7 per cent reported that they had tinnitus prior to their
      depressive and/or anxiety disorders. We conclude that it is of great importance
      to identify these emotional disturbances in patients suffering from tinnitus.

PMID- 11465296
TI  - Early detection of hearing impairment in a developing country: what options?
AB  - The concept of early detection is often predicated on a specified time-interval
      for optimal neural development in early childhood. This has been facilitated by
      advances in objective screening methods such as auditory brainstem response (ABR)
      and otoacoustic emissions (OAE). However, the prospects for this trend in
      developing countries remain doubtful, because of adverse socio-economic
      conditions. Consequently, the relative effectiveness of available tests was
      evaluated to determine the most viable option for mass screening based on
      findings from a broader study among 359 school entrants (mean age 6.7 years) in
      Lagos. The specificity of the questionnaire for detecting hearing loss was 94.0
      per cent as against 62.4 per cent for otoscopy and 84.0 per cent for
      tympanometry. The sensitivities for the three methods were 10.0 per cent, 56.0
      per cent and 52.0 per cent, while the positive predictive values were 21.7 per
      cent, 19.4 per cent and 34.6 per cent respectively. Notwithstanding its
      limitations, the administration of a well-structured questionnaire at school
      entry, complemented with parental education, may constitute the inevitable and
      immediate option for an early detection program in a developing country.

PMID- 11465297
TI  - ICRA noises: artificial noise signals with speech-like spectral and temporal
      properties for hearing instrument assessment. International Collegium for
      Rehabilitative Audiology.
AB  - Current standards involving technical specification of hearing aids provide
      limited possibilities for assessing the influence of the spectral and temporal
      characteristics of the input signal, and these characteristics have a significant
      effect on the output signal of many recent types of hearing aids. This is
      particularly true of digital hearing instruments, which typically include non
      linear amplification in multiple channels. Furthermore, these instruments often
      incorporate additional non-linear functions such as "noise reduction" and
      "feedback cancellation". The output signal produced by a non-linear hearing
      instrument relates to the characteristics of the input signal in a complex
      manner. Therefore, the choice of input signal significantly influences the
      outcome of any acoustic or psychophysical assessment of a non-linear hearing
      instrument. For this reason, the International Collegium for Rehabilitative
      Audiology (ICRA) has introduced a collection of noise signals that can be used
      for hearing aid testing (including real-ear measurements) and psychophysical
      evaluation. This paper describes the design criteria, the realisation process,
      and the final selection of nine test signals on a CD. Also, the spectral and
      temporal characteristics of these signals are documented. The ICRA noises provide
      a well-specified set of speech-like noises with spectra shaped according to
      gender and vocal effort, and with different amounts of speech modulation
      simulating one or more speakers. These noises can be applied as well-specified
      background noise in psychophysical experiments. They can also serve as test
      signals for the evaluation of digital hearing aids with noise reduction. It is
      demonstrated that the ICRA noises show the effectiveness of the noise reduction
      schemes. Based on these initial measurements, some initial steps are proposed to
      develop a standard method of technical specification of noise reduction based on
      the modulation characteristics. For this purpose, the sensitivity of different
      noise reduction schemes is compared by measurements with ICRA noises with a
      varying ratio between unmodulated and modulated test signals: a modulated
      unmodulated ratio. It can be anticipated that this information is important to
      understand the differences between the different implementations of noise
      reduction schemes in different hearing aid models and makes.

PMID- 11465298
TI  - Audiometric evaluation of bilaterally fitted bone-anchored hearing aids.
AB  - Bilateral fittings of bone-anchored hearing aids (BAHA) were evaluated in 25
      patients with at least 3 months experience with using two BAHAs. For all
      patients, air conduction hearing aids were contraindicated due to either
      recurrent otorrhoea or otitis externa (19 cases) or to congenital aural atresia
      (six cases). Candidacy for bilateral fitting was primarily based on symmetry of
      bone conduction thresholds. For all patients, measurements comprised sound
      localisation, speech recognition in quiet and in noise. In addition, in a
      subgroup of nine patients, release from masking for pure-tone stimuli in noise
      with interaural phase differences (binaural masking level difference. BMLD) was
      measured. The percentage of correct localisation judgments with 500-Hz and 2-kHz
      noise bursts increased significantly (p<0.01) from 22.2 per cent and 24.3 per
      cent for unilateral fittings to 41.8 per cent and 45.3 per cent for bilateral
      fittings, respectively. With unilateral fittings sound localisation judgments
      appeared to be strongly biased to the ipsilateral BAHA side. whereas with
      bilateral fittings, judgments were far more symmetrical. The speech reception
      threshold for sentences in quiet was significantly (p<0.01) better for the
      bilateral fittings compared to the unilateral fittings: 37.5 dBA versus 41.7 dBA.
      Speech recognition in noise was measured with the speech signal presented in
      front of the listener and a 65-dBA masking noise at either +90 degrees or -90
      degrees azimuth. For noise presented at the ipsilateral side of the first fitted
      BAHA, the signal-to-noise ratio was significantly reduced (p<0.01) from -0.7 dB
      for the unilateral fitting to -4.0 dB for the bilateral fitting. The speech
      reception threshold in noise was not significantly different (p>0.05) for
      unilateral and bilateral fittings when the noise was presented at the
      contralateral side of the first fitted BAHA. The results for the six patients
      with congenital atresia are comparable with those for the other patients. So,
      directional hearing and speech recognition in noise improve significantly with a
      second BAHA. The BMLD measurements showed a significant (p<0.01) release from
      masking of 6.1, 6.0 and 6.6 dB for 125-Hz, 250-Hz and 500-Hz stimuli,
      respectively. The BMLD effect of 4.1 dB at 1,000 Hz was not significant at the 5
      per cent level. The positive results with the bilateral fittings in quiet can be
      ascribed to increased stimulus levels due to diotic summation of signals from
      either side. The results for localisation, speech recognition in noise and BMLD
      measurements indicate that bilaterally fitted BAHAs do indeed (to some extent)
      result in binaural hearing.

PMID- 11465299
TI  - Economic evaluation of systemic treatments for cytomegalovirus retinitis in
      patients with AIDS.
AB  - OBJECTIVE: To determine the cost of using systemic therapy to treat newly
      diagnosed cytomegalovirus (CMV) retinitis in persons with AIDS. DESIGN: Incidence
      based simulation model of CMV treatment from a government payer perspective.
      SETTING: Swiss healthcare system. PATIENTS AND PARTICIPANTS: Patients with AIDS
      and newly diagnosed CMV retinitis. INTERVENTIONS: Patients were assigned to 1 of
      4 treatment regimens for induction and maintenance therapy: (i) intravenous (IV)
      cidofovir induction and maintenance (cidofovir IV/IV); (ii) IV foscarnet
      induction and maintenance (foscarnet IV/IV); (iii) IV ganciclovir induction and
      maintenance (ganciclovir IV/IV); and (iv) IV ganciclovir induction and oral (PO)
      ganciclovir maintenance (ganciclovir IV/PO). Following a second relapse, patients
      were assigned to one of the other regimens. MAIN OUTCOME MEASURES: Time to first
      and subsequent progression, duration of maintenance treatment and direct medical
      expenditures [1998 Swiss francs (SwF)] . RESULTS: The median time to first
      progression was longest for cidofovir IV/IV, followed by foscarnet IV/IV,
      ganciclovir IV/IV and ganciclovir IV/PO. Mean survival was 13 months and mean
      costs for this period in the base case were lowest in those initially treated
      with cidofovir (SwF146,742), followed by initial treatment with foscarnet IV/IV
      (SwF194,809), ganciclovir IV/PO (SwF195,190) and ganciclovir IV/IV (SwF243,964).
      Costs were most sensitive to changes in efficacy estimates. CONCLUSIONS: Of the
      regimens studied, initiation of treatment with systemic cidofovir appears least
      costly over a 13-month period.

PMID- 11465300
TI  - Economic evaluation of a new acellular vaccine for pertussis in Canada.
AB  - OBJECTIVE: Pertussis is a highly contagious infection affecting mainly children.
      Acellular pertussis vaccines were recently introduced in Canada based on evidence
      of improved safety and efficacy over whole cell vaccines, the current standard of
      care. The following study reports the economic impact of replacing the whole cell
      vaccine (wP) by a new acellular vaccine (aP) in the Ontario pertussis
      immunisation programme. DESIGN: For a hypothetical cohort of 100,000 children
      from birth to the age of 8 years, the costs and consequences of pertussis
      vaccination with either aP or wP were compared. A decision analytical model was
      constructed for vaccine delivery, treatment of pertussis cases and vaccine
      adverse events, with analyses from the viewpoints of the Ontario Ministry of
      Health and society. MAIN OUTCOME MEASURES AND RESULTS: The main outcomes were
      expected number of pertussis cases, hospitalisations, and workdays lost by
      parents. Data on vaccine effectiveness, pertussis incidence, and other parameters
      used in the model were from published literature. Costs were discounted at 5%,
      and extensive sensitivity analyses were undertaken. Over 8 years, in a cohort of
      100,000 children, the introduction of aP would prevent 10,500 cases of pertussis,
      avoiding 504 hospital admissions and 73,500 days of work absence. For Ontario,
      healthcare cost savings over the same period would amount to 275,585 Canadian
      dollars ($Can), and societal savings to $Can9,752,864

PMID- 11465301
TI  - Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane
      Collaboration methods for meta-analysis within economic evaluation.
AB  - OBJECTIVE: To assess the cost effectiveness of nasal calcitonin (Miacalcin)
      compared with no therapy, alendronate or etidronate in the treatment of
      postmenopausal women with previous osteoporotic fracture. DESIGN AND SETTING:
      Meta-analysis followed by economic analysis. PERSPECTIVE: A Canadian provincial
      Ministry of Health. METHODS: The meta-analysis of randomised controlled clinical
      trials was based on the recommendations of the Cochrane Collaboration. Economic
      analysis was conducted within a Markov model using probabilities and costs
      derived from Canadian sources. RESULTS: The meta-analysis found evidence of the
      positive effect of both nasal calcitonin and alendronate in reducing the risks of
      hip, wrist and vertebral fractures in postmenopausal women. However, there was a
      lack of evidence of the effect of etidronate on hip and wrist fractures. For a 65
      year-old woman, with 5 years' therapy, the incremental cost per quality-adjusted
      life-year (QALY) gained for nasal calcitonin was 46,500 Canadian dollars ($Can)
      compared with no therapy and $Can32,600 compared with etidronate (1998 values).
      Comparison with alendronate was highly sensitive to the inclusion of one specific
      trial. CONCLUSIONS: Given the results of the analysis, based on current evidence,
      nasal calcitonin can be considered at the margins of being cost effective when
      compared with no therapy. Compared with active therapy, nasal calcitonin can be
      considered more cost effective than etidronate, but its cost effectiveness versus
      alendronate is inconclusive.

PMID- 11465302
TI  - Gastrointestinal-related healthcare resource usage associated with a fixed
      combination of diclofenac and misoprostol versus other NSAIDs.
AB  - OBJECTIVE: To compare gastrointestinal (GI) healthcare resource use (HCRU) and
      associated costs in patients taking a fixed combination of diclofenac and
      misoprostol versus other nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS:
      We analysed a sample (49,033 patients) of the Government of Quebec Health
      Insurance Agency database. Patients were included in the study if they did not
      have GI events during the year preceding the date of their first NSAID
      prescription dispensing (the index date). Patients were followed up for 2 years.
      A 3-stage model was used to determine the factors that influenced the direct
      medical costs of GI HCRU: (i) a logistic regression model (model 1) to estimate
      the risk of GI HCRU; (ii) a linear regression model (model 2) to estimate the
      direct costs of GI HCRU for those who had such events; (iii) multiplying the
      estimated risks from model 1 by the estimated costs from model 2 gave the
      estimated direct costs of GI HCRU for all patients. STUDY PERSPECTIVE: Provincial
      government of Quebec, Canada. RESULTS: 1,533 patients were prescribed
      diclofenac/misoprostol at the index date and 10,540 another NSAID. Comorbidity
      markers were not significantly different between the 2 groups. Of the
      diclofenac/misoprostol patients, 23 (1.5%) were hospitalised for GI problems
      compared with 194 (1.8%) of the NSAID group; 403 (26.3%) of
      diclofenac/misoprostol patients used gastroprotective agents compared with 2,849
      (27.0%) of the NSAID patients; 118 (7.7%) of diclofenac/misoprostol patients had
      GI diagnostic tests compared with 682 (6.5%) of the NSAID patients. The average
      direct medical cost of GI HCRU was 310.52 Canadian dollars ($Can)/patient (1997
      values) in the diclofenac/misoprostol group compared with $Can231.19/patient
      (1997 values) in the NSAID group. When adjusted for baseline factors, the ratio
      of the total direct medical cost of GI HCRU in the diclofenac/misoprostol group
      to that of the NSAID group was 1.15 (95% confidence interval: 0.89, 1.48).
      CONCLUSIONS: Our data showed no significant differences in GI HCRU among patients
      taking diclofenac/misoprostol compared with those taking NSAIDs.

PMID- 11465303
TI  - Cost effectiveness of desirudin compared with a low molecular weight heparin in
      the prevention of deep vein thrombosis after total hip replacement surgery.
AB  - OBJECTIVES: This prospective pharmacoeconomic study analyses and discusses the
      cost effectiveness (expressed as cost per life-year gained) of desirudin in
      comparison with a low molecular weight heparin (LMWH), enoxaparin, as prophylaxis
      against deep vein thrombosis (DVT) in total hip replacement. METHODS: The cost
      effectiveness was analysed on the basis of results from a clinical trial that
      compared the recombinant hirudin, desirudin, with the LMWH, enoxaparin. The trial
      results regarding the incidence of DVT are included together with epidemiological
      data in a decision tree, simulating long term cost effectiveness of patients
      undergoing elective hip replacement. The model includes Markov processes
      simulating patients up to the age of 85 years, including the costs of DVT-related
      long term complications. RESULTS: The average total thrombosis-related cost per
      patient under prophylactic therapy with enoxaparin is 7,022 Swedish kronor (SEK)
      compared with SEK7,497 when using desirudin (1998 values). The total costs with
      desirudin are 7% higher. Prophylaxis with desirudin in those patients undergoing
      elective hip replacement surgery adds, on average, 7 days of life per patient
      when compared with treatment using enoxaparin. This is equivalent to 1.91
      additional years of life per 100 patients treated. The incremental cost
      effectiveness ratio of prophylaxis with desirudin in patients undergoing elective
      hip replacement surgery is SEK24,864 per life-year gained in comparison with
      enoxaparin. CONCLUSION: The present study demonstrates that prophylactic therapy
      with desirudin is a cost-effective approach for the prevention of DVT in patients
      undergoing total hip replacement.

PMID- 11465304
TI  - The cost effectiveness of tapered versus abrupt discontinuation of oral
      cyclosporin microemulsion for the treatment of psoriasis.
AB  - OBJECTIVE: To assess the cost effectiveness of tapered versus abrupt
      discontinuation of a microemulsion formulation of cyclosporin in patients with
      chronic plaque psoriasis. METHODS: A cost-effectiveness analysis was performed in
      parallel with a non-blind, multicentre, international clinical trial of the
      safety and efficacy of intermittent short courses of cyclosporin. Direct and
      indirect costs were considered within a 1-year period following randomisation.
      PATIENTS: Patients with chronic plaque psoriasis inadequately controlled with
      topical treatment. STUDY PERSPECTIVE: The study was conducted from a societal
      perspective and was performed using data from Canada, Spain, Turkey and the UK.
      MAIN OUTCOMES MEASURES: The health outcome used was the total number of systemic
      therapy-free days (STFDs) over the first year. The mean incremental cost
      effectiveness ratio (ICER) was determined by dividing the differences in average
      cost per patient by the differences in average STFDs per patient. RESULTS: The
      overall ICER was dominant because tapered discontinuation was associated with
      both lower costs and improved efficacy in comparison with abrupt discontinuation.
      Further analyses showed that tapered discontinuation was a cost-effective
      alternative to abrupt discontinuation therapy, even when a conservative
      definition for cost effectiveness was adopted. CONCLUSION: This cost
      effectiveness analysis demonstrated that tapering cyclosporin was more cost
      effective than abruptly stopping cyclosporin in patients with chronic plaque
      psoriasis.

PMID- 11465305
TI  - Lifestyle drugs: determining their value and who should pay.
AB  - Lifestyle drugs are used to alleviate or enhance: (i) lifestyle problems or
      conditions, regardless of the cause; and (ii) health problems for which the
      underlying cause is in the realm of personal responsibility. It is the particular
      use of a drug, rather than its inherent properties, that determines whether it is
      called a lifestyle drug. The increasing availability of, and high demand for,
      lifestyle drugs contributes to their expanding role in healthcare. In the absence
      of objective pharmacoeconomic data, the subjective value or cost effectiveness of
      these agents varies among patients, medical professionals, regulatory agencies
      and payors. Most nations rely on value systems that are implied, rather than
      clearly articulated. The aims of largely institutional payors, and the individual
      patients and their physicians do not always coincide, creating tensions over who
      should pay for these drugs. Cost-sharing between patient and payer, drug
      limitations and prior authorisation protocols are some methods used to manage
      access to these drugs. There is an urgent need to formulate coherent values,
      priorities and strategies for dealing with lifestyle drugs. To do this, local and
      national regulatory agencies, politicians, healthcare providers, insurers and
      patients need to formulate broad areas of consensus. Finally, we must not forget
      compassion for the patient as we apply the dictates of institutional policy.

PMID- 11465306
TI  - Hip fracture prevention: cost-effective strategies.
AB  - The available literature on cost benefit, cost effectiveness and cost utility of
      different drug and non-drug regimens in preventing hip fractures was reviewed.
      The cost of a hip fracture and of the different treatment regimens varied
      considerably from one country to another. In primary prevention, potential
      savings only exceeded costs in women over the age of 70 years treated with
      hormonal replacement therapy (HRT). In the case of HRT, treating those with low
      bone mineral density levels (secondary prevention) seems to be more cost
      effective than general treatment (primary prevention). There are few studies that
      have compared several different preventive regimens. Cost effectiveness is
      directly related to the cost of the regimen used because there is no significant
      difference in their effectiveness. That is, a high cost regimen such as
      bisphosphonates would be less cost effective than a low cost regimen such as HRT,
      judged from existing literature. High risk groups can be identified (nursing home
      residents) and treated with low cost interventions (calcium plus vitamin D or hip
      protectors). Considerable differences in the estimates used for the efficacy of
      different regimens in studies exist. Further studies comparing several hip
      fracture preventive regimens are required in order to establish the most cost
      effective strategy.

PMID- 11465307
TI  - Cost considerations in the use of anaesthetic drugs.
AB  - Anaesthetic drugs typically comprise approximately 5% or less of a hospital
      pharmacy budget, yet they are a common target for cost reduction measures. In
      particular, there is considerable pressure to use less costly products where
      alternatives exist and to limit the introduction of expensive new items. In
      considering strategies to reduce a departmental drug budget, or in defending
      against restrictions imposed from outside, it is important to consider all of the
      costs associated with anaesthetic drug delivery. These costs comprise not only
      the expense of the anaesthetic drugs themselves, but also fixed and variable
      costs associated with their delivery and related to their effects. Elimination of
      drug waste will always be beneficial, since it has no direct effect on the
      patient yet clearly reduces cost. Waste is by no means confined to anaesthetic
      drugs, however. Using less expensive drugs may appear an attractive option and
      can reduce costs, provided that patient outcome is in no way affected. Rarely is
      this the case. Once patient care is modified, through changes in recovery times
      or complication rates, determining the true cost of the intervention becomes
      essential; there may be increases in indirect costs which dwarf the apparent
      savings. Sometimes indirect costs will rise by a lesser amount than savings in
      direct costs, such that there is still an overall benefit but less than that
      originally anticipated. Exactly how indirect effects result in indirect costs is
      highly variable. The requirement for additional drugs or supplies to treat an
      adverse event, such as emesis, will always have an associated cost. Delayed
      recovery or prolonged hospital stay will waste operating room time or increase
      the amount of time that a patient requires nursing care, but whether this carries
      an associated cost depends on what the staff would otherwise have been doing.
      Depending on the employment method, staff may have been sent home early (with
      less pay) or employed at identical cost but with less to do. Many studies which
      purport to consider all costs either ignore such issues, or make invalid
      assumptions. These issues are complex, but anyone involved with decisions
      concerning anaesthetic costs should be familiar with the underlying principles
      and be able to make a rational assessment of the likely indirect costs in their
      own institution.

PMID- 11465308
TI  - The lifetime cost of bipolar disorder in the US: an estimate for new cases in
      1998.
AB  - OBJECTIVE: To develop a cost model that estimates the total and per case lifetime
      cost of bipolar disorder for 1998 incident cases in the US. STUDY DESIGN:
      Lifetime cost simulation model. PERSPECTIVE: Societal. METHODS: Age- and gender
      specific incidence of bipolar disorder in 1998 was estimated by simulation based
      on existing prevalence data. The course of illness and mental health service cost
      of 6 clinically defined prognostic groups was estimated based on the research
      literature and the judgement of panels of experts. Excess cost of general medical
      care was estimated based on claims data from a large insurer. Indirect cost was
      projected including excess unemployment and reduced earnings reported in the
      National Comorbidity Survey. Comorbidity treatment and indirect cost related to
      alcohol (ethanol) and drug abuse was added based on a National Institute on Drug
      Abuse study. RESULTS: The present value of the lifetime cost of persons with
      onset of bipolar disorder in 1998 was estimated at 24 billion US dollars ($US).
      Average cost per case ranged from $US11,720 for persons with a single manic
      episode to $US624,785 for persons with nonresponsive/chronic episodes.
      CONCLUSION: The model indicates the potential cost savings of preventing a case
      of bipolar disorder and underscores the importance of achieving a stable outcome
      in new cases to limit the economic consequences of the disorder.

PMID- 11465309
TI  - Cost effectiveness of ramipril in patients with non-diabetic nephropathy and
      hypertension: economic evaluation of Ramipril Efficacy in Nephropathy (REIN)
      Study for Germany from the perspective of statutory health insurance.
AB  - BACKGROUND: In the Ramipril Efficacy In Nephropathy (REIN) trial, ramipril
      significantly lowered the rate of reaching the combined end-point of doubling of
      baseline serum creatinine levels or end-stage renal failure (ESRF). OBJECTIVE: To
      determine the additional cost per patient-year of chronic (long term) dialysis
      avoided (PYCDA) when the ACE inhibitor, ramipril, was added to conventional
      treatment of patients with non-diabetic nephropathy and hypertension. STUDY
      PERSPECTIVE: Statutory Health Insurance (SHI) provider in Germany. DESIGN AND
      SETTING: Data from the REIN Study were used in a cost-effectiveness analysis
      (CEA). A modelling approach was used, which was based on secondary analysis of
      published data, and costs were those incurred by the SHI provider (i.e. SHI
      expenses). In the base-case analysis, average case-related SHI expenses were
      applied and PYCDA were quantified using the cumulative incidence of ESRF as
      observed in the REIN trial. MAIN OUTCOME MEASURES AND RESULTS: The incremental
      cost-effectiveness ratios (ICERs) of ramipril varied between about -76,700
      deutschmarks (DM) and -DM81,900 per PYCDA (DM 1 approximately equals 0.55 US
      dollars; 1999 values), according to the treatment periods of 1 year and 3 years,
      respectively. In the sensitivity,analysis, the robustness of the model and its
      results were shown when the extent of influence of different model variables on
      the base-case results was investigated. First, probabilities of ESRF and PYCDA
      were estimated according to the Weibull method. Second, the influence of the
      model variables on the target variable was quantified using a deterministic
      model. Third, the dependency of the target variable (ICER) on random variables
      was described in a simulation. The cost for chronic dialysis had by far the
      greatest impact on the target variable, which was 28 times greater than the
      impact of clinical effectiveness of ramipril, i.e. the number of PYCDA. There
      were net savings per PYCDA with ramipril treatment after 1, 2 and 3 years: 95% of
      the 10,000 simulation steps resulted in savings of between DM69 500 and D94,600
      per PYCDA after 3 years. CONCLUSIONS: Results from this evaluation show that
      ramipril offers enormous savings from the perspective of the SHI provider (third
      party payer) in Germany when added to the conventional treatment of patients with
      non-diabetic nephropathy and hypertension.

PMID- 11465310
TI  - The cost of inadequate prescriptions for hypolipidaemic drugs. VICAF Group.
AB  - BACKGROUND: The high consumption of hypolipidaemic agents warrants the study of
      the costs caused by these medicines being inadequately prescribed. OBJECTIVE: To
      quantify the economic cost generated in 1 year in primary care by inadequate (or
      unnecessary) prescriptions for hypolipidaemic drugs. METHODS: A cross-sectional
      study based on hypolipidaemic drug prescriptions for a population of pensioners
      ordered during 1 year by 49 family physicians from 4 health areas in Madrid,
      Spain. Each doctor completed a data collection sheet for each patient for whom a
      hypolipidaemic agent was prescribed. The adequacy of each prescription was
      evaluated according to 2 quality levels: for level 1, it was necessary to have
      knowledge of the following parameters: total cholesterol level at the start of
      treatment, low density lipoprotein cholesterol (LDL-C) level, whether dietary
      intervention preceded pharmacological treatment, patient age and risk factors;
      for level 2, it was not necessary to have knowledge of either diet before
      pharmacological treatment or LDL-C levels. Inadequate expenditure was quantified
      by physician, by type of doctor who initiated the pharmacological treatment (the
      family physician, specialist, other doctor), therapeutic group and agent. STUDY
      PERSPECTIVE: Primary healthcare management of 4 public health areas. RESULTS: The
      cost of inadequate prescriptions for hypolipidaemic drugs reached 116,480.60 US
      dollars ($US; 1997 values) for quality level 1 and $US37,893.37 for level 2.
      12.3% of the health professionals ordered all their prescriptions inadequately
      (level 1). Of the total inadequate prescription expenditure, 20.4% represented
      treatments initiated by family physicians and 35.3% by specialists (level 1).
      Statins made up 78.2% of the total cost; the inadequate expenditure for this
      therapeutic group reached $US88,797 (level 1). Of the prescriptions for fibrates,
      88% were inadequate (level 1). CONCLUSIONS: In this study, 67% of prescriptions
      for hypolipidaemic medicines were ordered inadequately in the pensioner
      population, which represents a considerable pharmacological expenditure. This
      percentage and the mean cost per inadequate prescription was higher if a
      specialist was the professional initiating the treatment. Therefore, it is
      necessary to run pharmaceutical prescription quality programmes with both primary
      care physicians and specialists involved.

PMID- 11465311
TI  - Cost effectiveness of selective decontamination of the digestive tract in liver
      transplant patients.
AB  - OBJECTIVE: To assess the cost effectiveness of selective decontamination of the
      digestive tract (SDD) in liver transplant patients. DESIGN: Randomised, placebo
      controlled, double-blind trial with an integrated economic evaluation. SETTING:
      Two university hospitals in The Netherlands. Cost effectiveness was assessed from
      a societal perspective. PATIENTS AND PARTICIPANTS: 58 patients who underwent
      liver transplantation and received SDD (n = 29) or placebo (n = 29) pre- and
      postoperatively. INTERVENTIONS: SDD medication and placebo. MAIN OUTCOME
      MEASURES: Infection episodes, days of infection, costs of SDD and routine
      cultures, mean other direct medical costs per patient and additional costs of
      severe infection. RESULTS: Costs of SDD medicine and routine cultures were on
      average 3,100 US dollars ($US; 1997 values) per patient who underwent SDD. Both
      preoperatively and postoperatively, costs other than SDD and cultures did not
      significantly differ between the SDD and the placebo groups (preoperative,
      $US2,370 vs $US2,590; postoperative, $US25,455 vs $US24,915). Additional
      postoperative costs of severe infections were $US250 per day per patient. There
      were no significant differences in the mean number of infection episodes between
      groups. CONCLUSIONS: SDD leads to the additional costs of SDD medication and
      routine cultures, whereas no savings in other costs and no improvement in
      infection episodes are realised. Consequently, SDD may be considered as a
      nonefficient approach in patients undergoing liver transplantation. The
      additional costs of severe infection are considerable.

PMID- 11465312
TI  - AGE-RAGE interactions: sticky sugar kills.

PMID- 11465313
TI  - Uterine artery embolisation for treatment of fibroids: experience in Chinese
      women.
AB  - Twelve women with symptomatic fibroids were treated with transcatheter uterine
      artery embolisation with the use of polyvinyl alcohol (PVA) particles. For the
      nine women who were due for follow-up, reduction in uterine volume and dominant
      fibroid size were observed on magnetic resonance imaging. All the nine women had
      normal luteinising hormone (LH) and follicle stimulating hormone (FSH) levels
      before the procedure and during the follow-up. Seven of the nine women reported
      noticeable symptomatic improvement during the follow-up. Pain experienced was of
      variable level, but well controlled. Adequate analgesia is essential for the
      procedure. Longer follow-up and prospective fertility studies are required to
      evaluate the long-term effects before this procedure could be safely extended to
      younger age groups.

PMID- 11465314
TI  - The value of pre-operative high resolution CT scans in cholesteatoma surgery.
AB  - INTRODUCTION: Cholesteatoma is traditionally diagnosed by otoscopic examination
      and treated by explorative surgery. The need for imaging in an uncomplicated case
      is contentious. This study assesses the usefulness of a pre-operative high
      resolution CT scan in depicting the status of the middle ear structures in the
      presence of cholesteatoma. MATERIALS AND METHODS: The surgical findings of 36
      ears with cholesteatoma operated on by the first author were retrospectively
      compared with the CT findings reported on by the second author. The following
      were analysed: diagnostic features of cholesteatoma on CT, status of the middle
      ear structures (ossicles, facial nerve canal, semicircular canals and tegmen
      tympani), and presence of any anatomical variations and disease complications.
      RESULTS: All cases had at least 1, and 30 cases (83.3%) had all, of the following
      radiological features: (a) a non-dependent tissue mass, (b) a location typical
      for cholesteatoma and (c) bony erosion. The radiosurgical agreement was excellent
      for the malleus (kappa statistics, k=0.83), stapes (0.94) and semicircular canals
      (0.8), good for the incus (0.62) and tegmen (0.65), but poor for the facial nerve
      canal (0.3). Potential surgical hazards detected by the scans included: low lying
      dura, high jugular bulb, anterior lying sigmoid sinus, facial nerve dehiscence
      and other situations brought about by the destructive nature of the lesion.
      CONCLUSION: There is good to excellent radiosurgical correlation in cholesteatoma
      for most middle ear structures except for the integrity of the facial canal. The
      scan alerts the surgeon to potential surgical dangers and complications of
      disease. High-resolution CT scan is an important investigative tool prior to
      cholesteatoma surgery.

PMID- 11465315
TI  - Multiple level pharyngeal surgery for obstructive sleep apnoea.
AB  - The aim of the study is to evaluate the results of multiple level pharyngeal
      surgery in patients with moderate to severe obstructive sleep apnoea in Changi
      General Hospital, Singapore. 13 patients who failed non-surgical treatment
      underwent surgery which includes uvulopharyngopalatoplasty, genioglossal
      advancement and modified hyoid myotomy and suspension. Epworth sleepiness scale,
      Cephalometric analysis and Sleep study were performed pre- and post-operatively
      to evaluate the results. 76.9% of the patients achieved more than 50% reduction
      in AHI with post-operative AHI of less than 20. Cephalometric analysis showed an
      average of 5.2 mm increase in posterior airway space. All patients achieved
      improvement in Epworth sleepiness scale with an average improvement of 11.8
      points. The mean follow-up period of the 13 patients is 12.6 months. Our
      preliminary results suggest that multiple level pharyngeal surgery is an
      effective option in the treatment of moderate to severe obstructive sleep apnoea.

PMID- 11465316
TI  - Extrahepatic bile duct length in the Singapore population.
AB  - BACKGROUND: Although the length of the common bile duct is well documented, the
      length of extrahepatic biliary tree is less well studied, particularly in among
      the Asian population. The extrahepatic bile duct (BD) length is defined as the
      measurement from the hepatic hilum to the papilla. OBJECTIVE: This study was
      performed to assess the normal range of extrahepatic BD length, as defined above,
      in the Singapore population. This information would be useful in assisting the
      local endoscopy unit in procuring the different lengths of biliary stents.
      METHOD: Between 1.8.96 to 1.12.97, 486 cholangiograms were obtained post-ERCP, of
      which only 100 cholangiograms that were representative of a non-distorted BD were
      used for analysis. The BD length, taken from the mid-point of the confluence of
      the left and right hepatic ducts at the hilum to the papilla, was measured with a
      string placed on the cholangiogram. The true length was obtained after correction
      for radiological magnification. RESULTS: The range of bile duct lengths followed
      a normal distribution curve with a mean length of 9.6 cm. The range was from 6.9
      cm to 12.6 cm. With respect to the length of stents commonly deployed, the
      cumulative percentage of BD length less than and equal to 7-, 9-, 10- and 12-cm
      were 1%, 38%, 57% and 98% respectively. CONCLUSION: From a practical point of
      view, this study suggests that endobiliary stent of 5 cm in length should be
      readily available for drainage of distal CBD strictures as 1% of our population
      has BD length less than 7 cm. However, as 2% of the population has BD length
      greater than 12 cm, 15 cm stents should be available in the endoscopy unit for
      drainage of hilar obstructions/strictures.

PMID- 11465317
TI  - Risperidone in the treatment of first episode psychosis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of risperidone in Singapore
      patients with first-episode psychosis in an eight-week open label prospective
      study. METHOD: Previously untreated male and female patients aged 18 - 65 with
      DSM IV schizophreniform disorder or DSM IV schizophrenia for no longer than 12
      months were recruited from Woodbridge Hospital and Geylang Psychiatric Outpatient
      Clinic. Patients were treated with risperidone for 56 days. Outcome was assessed
      with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global
      Impression scale (CGI). Safety was assessed by monitoring of vital signs and by
      comparing the frequency of adverse events (AEs) before and after treatment.
      RESULTS: 24 patients with a mean age of 33.29+/-9.12 years and a mean duration of
      illness of 166.5+/-111.4 days (median 180 days) were included. The mean
      risperidone dosage was 2.7 mg +/- 1.0 at day 56. Mean PANSS total scores reduced
      by 50.21% from 88.29+/-21.55 at baseline to 43.96+/-7.5 at endpoint (p < 0.001).
      The responder rate (> or = 20% reduction in the total PANSS score) was 87.5%. 13
      patients (54.2%) exhibited a 50% or greater reduction in total PANSS score.
      Except for item G5 (mannerisms and posturing) all single PANSS items were reduced
      significantly. The CGI scores of all patients improved at endpoint. No serious
      adverse events were reported. CONCLUSIONS: Overall the therapy of first-episode
      psychosis patients with risperidone was effective and safe.

PMID- 11465318
TI  - Gallstone granuloma: a rare complication of laparoscopic cholecystectomy.
AB  - Gallstone spillage during laparoscopic cholecystectomy is a relatively common
      occurrence. These intraperitoneal stones rarely give rise to complications. We
      present the case of a 68 female who presented with a 5 cm diameter epigastric
      mass two years after a laparoscopic cholecystectomy for acute-on-chronic
      cholecystitis with gallbladder stones. CT abdomen demonstrated an inflammatory
      mass with central calcification. Laparotomy and excision of the mass revealed the
      diagnosis as a gallstone granuloma.

PMID- 11465319
TI  - A case of hypersensitivity to gelafundin.
AB  - We report a case of cardiovascular collapse after gelafundin infusion, a commonly
      used colloid. Risk factors for such a reaction and suggested alternative are
      reviewed. Awareness of this reaction is highlighted in view of its increasing
      popularity.

PMID- 11465320
TI  - Familial autoimmune myasthenia gravis.
AB  - Familial Autoimmune Myasthenia Gravis (FAMG) is rarely reported. We present a
      mother and son with late-onset mild to moderate ocular disease, low acetylcholine
      receptor antibody titre and the absence of a thymoma. Both responded well to low
      doses of anticholinesterase. HLA typing revealed that they did not share the
      usual HLA antigens or haplotypes with that previously reported in Caucasian and
      Chinese sporadic Myasthenia Gravis. Chinese FAMG may be associated with HLA
      antigens different from that of sporadic MG.

PMID- 11465321
TI  - Nodular anterior scleritis associated with ocular trauma.
AB  - It is accepted that ocular trauma may be the precipitant of non-infectious
      uveitis. We report the case of a patient who developed unilateral nodular
      anterior scleritis following ocular trauma. Infection and systemic inflammatory
      diseases were excluded as causes of the inflammation. Our observations suggest
      the possibility that ocular trauma may act as a trigger for scleritis.

PMID- 11465322
TI  - Clinics in diagnostic imaging (60). Insufficiency fractures of the pelvis.
AB  - An 80-year-old woman presented with severe low back pain of gradual onset. Her
      walking ability was affected. Physical examination was essentially negative. Bone
      scintiscans showed a butterfly-shaped area of increased sacral uptake as well as
      focal pubic uptake. The diagnosis of sacral and parasymphyseal insufficiency
      fractures was confirmed by CT. The patient recovered well with conservative
      management. The clinical and imaging features, and management of insufficiency
      fractures of the pelvis are discussed.

PMID- 11465323
TI  - Patient-controlled analgesia during SWL treatments.
AB  - PURPOSE: To identify the factors that influence analgesic consumption during SWL
      on the Dornier Lithotripter U/50. PATIENTS AND METHODS: In Group 1 (N = 152),
      analgesia was induced with propofol 0.8 mg/kg and alfentanil 8 microg/kg. In
      Groups 2 (N = 78) and 3 (N = 250), the induction dose was reduced by 20%. For all
      patients, the maintenance dose was propofol 0.25 mg/kg and alfentanil 5 mg/kg
      administered with a patient-controlled analgesia (PCA) device. Groups 1 and 2 had
      SWL with the EMSE 220 shockwave emitter, whereas Group 3 was treated with the
      EMSE F150. Data were collected on treatment, total drug doses, and side effects.
      RESULTS: There was no significant difference in PCA dose among the groups, but
      analgesic consumption was lower in patients treated with the EMSE F150. Except in
      Group 2, analgesic consumption tended to decrease with age until age <70. The 20%
      reduction in the induction dose did not cause an increase in PCA usage. Analgesic
      consumption was higher for kidney than for ureteral stones and was highest for
      stones in renal pelvis. Consumption was lower for larger stones than for smaller
      stones and higher for patients receiving more shockwaves. Almost one quarter of
      patients in Group 1 exhibited transient O2 desaturation during induction, an
      effect that was less common in the other groups. Ventricular premature beats were
      detected only during treatment of stones above the ureteropelvic junction.
      CONCLUSIONS: Intravenous administration of a combination of alfentanil and
      propofol via a PCA device is an elegant, reliable, and safe method of
      analgesosedation for SWL. Patient satisfaction is high, and side effects are
      uncommon. Faster turnover of patients is possible.

PMID- 11465324
TI  - Comparison of shockwave lithotripsy outcomes in patients receiving sufentanil or
      lidocaine spinal anesthesia.
AB  - PURPOSE: To determine whether the use of intrathecal sufentanil, which allows the
      patient to move during shockwave lithostripsy (SWL), affects treatment outcomes
      and operative and recovery times compared with standard lidocaine spinal
      anesthesia. PATIENTS AND METHODS: We retrospectively studied a series of 62 SWL
      procedures performed on an unmodified Dornier HM3 lithotripter. The mean calculus
      size was 10.7 mm. There were 46 renal calculi, 13 ureteral calculi, and 4
      patients with calculi in both locations. Of the 63 procedures, 25 were performed
      using intrathecal sufentanil alone, and 37 were performed with intrathecal
      lidocaine with or without additional agents. We compared treatment outcomes, as
      well as treatment time, fluoroscopy time, postanesthesia care unit (PACU) time,
      time to voiding, and time to ambulation. RESULTS: Sufentanil use was associated
      with a significantly higher rate of successful treatment, defined as residual
      fragments absent or <4 mm on follow-up imaging, compared with lodocaine: 68% v.
      40% (p = 0.0394). There was no significant difference between the groups in
      treatment time or fluoroscopy time. Use of sufentanil was associated with
      significantly shorter PACU time, time to ambulation, and time to voiding
      postoperatively. These differences persisted when men and women were analyzed
      separately, although the differences were less significant in women. CONCLUSIONS:
      The use of intrathecal sufentanil for anesthesia during SWL does not adversely
      affect treatment outcome; it is, in fact, associated with better outcomes. The
      advantages of this agent in shortening recovery times and in easing patient
      transfer into the HM3 gantry argue for increasing its use.

PMID- 11465325
TI  - New-generation lithotripters for treatment of patients with implantable
      cardioverter defibrillator: experimental approach and review of literature.
AB  - PURPOSE: The influence of shockwaves applied during extracorporeal shockwave
      lithotripsy on the function of implantable cardioverter defibrillators was
      evaluated. Mechanical influences as well as proper electrical function were
      tested in an experimental approach. MATERIALS AND METHODS: Two implantable
      defibrillators (Ventak Mini 1743 and AVII 1821) were exposed to the shockwaves of
      a new-generation lithotripter. Each of the antidysrhythmic devices was tested at
      several distances from and within the focus of the lithotripter. All studies were
      performed with maximum energy and the number of shockwaves used for stone
      treatment. The devices were connected to an ECG simulator, and continuous
      recording of a surface ECG, a shock ECG, and marker channel was performed.
      RESULTS: No macroscopic and microscopic mechanical damage was observed. The
      detection function of the implantable defibrillators was not altered by any
      electromagnetic artifacts even when brought into the focus of the shockwaves. All
      induced ventricular dysrhythmias were terminated properly regarding artifact
      sensing. However, after defibrillation, the pacing function of the Ventak Mini
      cardioverter defibrillator, which was programmed into the demand mode, failed. In
      this case, there was no post-shock pacing in the period of post-defibrillation
      asystole. The failure was caused by artifact oversensing. CONCLUSION: In patients
      with implanted cardiac devices undergoing treatment with a new-generation
      lithotripter, deactivation of the defibrillator is not mandatory. For safety
      reasons, continuous ECG recording is recommended. To avoid pacing failure by
      artifact oversensing, the shockwaves should be applied in a R-wave synchronous
      mode.

PMID- 11465326
TI  - Endoluminal sonographic imaging of upper urinary tract: three-dimensional
      reconstruction.
AB  - Two-dimensional endoluminal sonographic imaging of the ureter demonstrates the
      periureteral anatomy, as well as define lesions within the ureteral wall. It has
      been used for evaluation of a wide range of abnormalities, including
      ureteropelvic junction (UPJ) obstructions, crossing vasculature at an obstructed
      UPJ, ureteral and renal pelvic neoplasms, and the obstructed ureter. Three
      dimensional (3D) reconstruction of two-dimensional (2D) sonographic imaging is a
      new technique applicable to intraluminal imaging. It offers advantages over 2D
      imaging by demonstrating the spatial relation of anatomic structures that cannot
      be appreciated using conventional imaging. We have evaluated a number of ureters
      with various pathology using 2D endouminal sonography. In this paper, we present
      three cases in which we have used 3D reconstruction to gain a clearer
      understanding of the pathology. Although still early in its application, 3D
      endoluminal reconstruction has potential to be a clinically useful aid to
      surgical decision-making.

PMID- 11465327
TI  - Percutaneous nephrolithotomy in patients aged 60 years or older.
AB  - PURPOSE: To assess the safety and efficacy of percutaneous nephrolithotomy in
      patients more than 60 years old. PATIENTS AND METHODS: We retrospectively
      evaluated and compared the data of 28 percutaneous nephrolithotomies (PCNL)
      performed on 27 patients aged 60 years and older (mean 65.8) with the data of the
      remaining 178 PCNL procedures on 166 patients performed in our clinic between
      December 1997 and December 1999. RESULTS: Although staghorn stones seemed to be
      more common in the elderly group (25% v 22%), no statistical significance was
      demonstrated (P = 0.715), and the stone burden was similar for the two groups (P
      = 0.112). The only interesting finding in terms of patient characteristics was a
      significantly higher incidence of solitary kidney in patients aged 60 years or
      older (29% v 7%; P = 0.003). The success rates (stone-free patients and patients
      with residual stones <4 mm) were similar, being 89% for the elderly group and 92%
      for the younger patients (P = 0.718). Transfusion rates were also similar (21.4%
      in the elderly v 18% in the younger group; P = 0.662). No significant
      complication was observed in this elderly group, and no renal deterioration has
      been detected even in the follow-up of patients with a solitary kidney.
      CONCLUSIONS: Despite the somewhat higher stone burden in the elderly patients
      (1077.92 mm2 v 920.85 mm2), the stone-free rate was similar to that obtained in
      the younger patients, without any higher rates of complications or blood
      transfusions or longer hospital stay. Percutaneous nephrolithotomy is a safe and
      effective method of stone treatment in the elderly, even if they have a solitary
      kidney or complex calculi.

PMID- 11465328
TI  - Flexible ureteroscopic lithotripsy: first-line therapy for proximal ureteral and
      renal calculi in the morbidly obese and superobese patient.
AB  - BACKGROUND AND PURPOSE: The surgical treatment of kidney and proximal ureteral
      stones in morbidly obese patients (>14 kg/m2) remains difficult because shockwave
      lithotripsy is precluded by weight limitations and percutaneous nephrolithotomy
      is associated with difficult access and a high (9%) rate of transfusion. We
      review our experience with retrograde ureteroscopic lithotripsy in morbidly obese
      patients with renal and proximal ureteral stones. PATIENTS AND METHODS: Between
      December 1992 and April 2000, five women and three men with a mean age of 46.5
      years (range 33-68 years) and a mean body mass index of 54 (range 45-65.2)
      underwent 10 independent ureteroscopic procedures for urolithiasis. The average
      stone size was 11.1 mm (range 5-25 mm). Lithotripsy was performed with the
      holmium laser in eight patients (60%) the electrohydraulic lithotripter in four
      (30%), and the tunable-dye laser in the remaining patient. Stone-free status was
      defined as no stones visible on a plain film with nephrotomograms or CT scan at 3
      months. RESULTS: The mean operation time was 101 minutes (range 45-160 minutes),
      and 60% of the procedures were done on an outpatient basis. After the initial
      procedure, the stone-free rate was 70%. Two patients had fragments <4 mm, and no
      further therapy was undertaken. There was one complication: transient renal
      insufficiency (serum creatinine concentration 3.7 mg/dL) secondary to
      aminoglycoside toxicity. No transfusions were needed. CONCLUSION: In the morbidly
      obese patient with symptomatic stones <1.5 cm, ureteroscopic lithotripsy is safe,
      successful, and efficient.

PMID- 11465329
TI  - Ergonomic problems associated with laparoscopy.
AB  - PURPOSE: Failure to understand the ergonomics of laparoscopic surgery has a
      potential to pose health problems for the surgeons. This study was planned to
      assess the prevalence, significance, and awareness of ergonomic problems
      associated with laparoscopy. MATERIAL AND METHODS: A questionnaire designed to
      assess the frequency and degree of physical discomfort practicing surgeons
      experienced and their awareness of the responsible factors was distributed to
      approximately 350 attendees of the Live International Workshop and CME on
      Laparoscopic Urologic Surgery. The response sheets were analyzed. RESULTS: Two
      hundred four attendees completed the questionnaire, of whom 131 were performing
      laparoscopic surgery (Group A). The rest (N = 73) were practicing only
      conventional surgery (Group B). The correct answer to the pictorial question,
      which tested the correct grip technique, was 81% and 56% in Group A and B,
      respectively (P = 0.0003). Group A surgeons were significantly (P = 0.04) better
      at answering the questions on neurapraxia. There was a statistically significant
      (P = 0.004) increase in the frequency of finger numbness and eye strain in Group
      A surgeons compared with Group B. Within Group A, finger numbness (P = 0.03) and
      eye strain (P = 0.002) were significantly greater in the junior laparoscopic
      surgeons than in senior laparoscopic surgeons. Surgeons having <2 years of
      laparoscopic surgical experience were significantly more affected. CONCLUSIONS:
      Surgeons performing laparoscopy have significant ergonomic problems, especially
      finger numbness and eye strain. Junior laparoscopic surgeons and surgeons with <2
      years of laparoscopic surgical experience are more affected.

PMID- 11465330
TI  - Retroperitoneoscopic adrenalectomy: lateral approach.
AB  - Laparoscopy has become the essential surgical approach to the adrenal gland at
      many institutions, including ours. At the Cleveland Clinic, laparoscopic
      adrenalectomy for benign and malignant adrenal neoplasms can be performed by
      either the transperitoneal or the retroperitoneal approach. Herein, we present
      our technique of lateral retroperitoneal laparoscopic adrenalectomy.

PMID- 11465331
TI  - Hand-assisted laparoscopic radical nephrectomy: the experience of the
      inexperienced.
AB  - PURPOSE: We retrospectively examined the experience of novice laparoscopic
      surgeons performing hand-assisted laparoscopic radical nephrectomy. The purpose
      was to determine if urologists with minimal laparoscopic training could perform
      hand-assisted laparoscopic nephrectomies in a safe and efficient manner.
      MATERIALS AND METHODS: The first six hand-assisted laparoscopic radical
      nephrectomies performed by four different urology residents at the Chicago
      Lakeside VA hospital were reviewed. The residents included three chief urology
      residents and one postgraduate year 3 urology resident. None of the residents had
      taken any laparoscopic course, and all had limited exposure to the hand-assisted
      technique. In all cases, the residents performed the entire operation. The
      patients were evaluated for operative time, tumor size, body mass index, and ASA
      score. RESULTS: All six procedures were completed without conversion to the open
      technique. The average operating time was 215.8 minutes, and the time from
      incision to organ removal averaged 140.8 minutes. The average estimated blood
      loss was 166 mL. Complications included an intraoperative diaphragmatic injury
      (recognized and repaired laparoscopically) and one postoperative ileus.
      CONCLUSION: Hand-assisted laparoscopic radical nephrectomy can be performed
      safely and efficiently by urologists with minimal laparoscopic experience.

PMID- 11465332
TI  - Laparoscopic nephrectomy: prediction of outcome in relation to the preoperative
      risk factors in two approaches.
AB  - PURPOSE: The data on laparoscopic nephrectomy in Mansoura Urology & Nephrology
      Center were reviewed to identify the preoperative findings that may predict the
      need for conversion to open surgery. PATIENTS AND METHODS: One hundred sixty
      three patients were subjected to transperitoneal laparoscopic nephrectomy, while
      82 underwent retroperitoneal laparoscopic nephrectomy for benign renal diseases.
      The preoperative demographic data and laboratory and radiologic findings of these
      patients were correlated with failure rate of the laparoscopic procedure.
      RESULTS: The overall failure rate was 10.4% and 11% for the transperitoneal and
      retroperitoneal approach, respectively. Positive urine culture, renographic
      clearance of the removed kidney (>10 ml/min), and learning curve were
      independently associated with a greater risk of failure in patients undergoing
      transperitoneal nephrectomy. For the retroperitoneal approach, a positive urine
      culture, renographic clearance (> or =10 ml/min), and large kidney showed
      statistical significance. CONCLUSION: Preoperative data could be used as a
      predictor of laparoscopic nephrectomy outcome in patients with benign renal
      diseases. A more experienced surgeon should be selected for risky cases, bearing
      in mind the greater potential for early conversion to open surgery.

PMID- 11465333
TI  - Retroperitoneoscopic pyelolithotomy via a posterior approach for large impacted
      renal pelvic stone.
AB  - Retroperitoneal laparoscopic pyelolithotomy via a posterior approach was
      successful in a patient with a large impacted renal pelvic stone. This procedure
      is beneficial as an alternative to open surgery for stones that cannot be treated
      by SWL or intracorporeal lithotripsy. This procedure may also be the initial
      treatment in selected cases.

PMID- 11465334
TI  - Low-power holmium laser for the management of urinary tract calculi, structures,
      and tumors.
AB  - BACKGROUND AND PURPOSE: Introduction of the holmium laser has provided an
      indispensable tool for the management of urinary tract stones, strictures, and
      superficial urothelial tumors. While full-power holmium lasers are required for
      laser resection of the prostate, lower-power devices can be utilized for all
      cases of stone fragmentation and stricture incision and most cases of superficial
      urothelial tumors. Herein, we report our initial experience in utilizing a low
      power holmium laser in our endourologic practice. PATIENTS AND METHODS: Over a 6
      month period, we have utilized both low-power (25 W) and full-power (80 W)
      holmium lasers to fragment urinary tract stones, incise ureteral or urethral
      strictures, and ablate superficial urothelial tumors. A series of 80 consecutive
      patients were assessed prospectively. Laser fibers with a diameter of 200 microm
      and 365 microm were employed with power settings of 6.4 to 10 W. Laser fiber size
      and power settings were similar for the low- and full-power devices. RESULTS:
      Overall, 95% of the stones were completely fragmented, with a stone-free rate at
      3 months of 92%. All strictures were incised, with a 91% patency rate at 3
      months. Complete tumor ablation was attained in 70%, with a tumor-free rate of
      60% at 3 months. Results were equivalent for the low- and full-power lasers. The
      200-microm laser fiber allowed adequate access throughout the upper urinary tract
      during flexible ureteroscopy and flexible nephroscopy. The 365-microm laser fiber
      was employed via rigid and semirigid endoscopes. CONCLUSIONS: A low-power holmium
      laser supplies adequate fragmentation and incision power for virtually all
      endourologic cases. It also provides ablative power in most situations. The only
      current urologic application that cannot be performed with the low-power device
      is laser prostatic resection, which requires 60 to 80 W of power. The reduced
      power holmium laser should be considered as a low-cost alternative for the
      management of urinary tract stones, strictures, and urothelial tumors, especially
      in centers where laser prostatic resection is not performed.

PMID- 11465335
TI  - Contractile function of upper urinary tract after indwelling ureteral prosthesis:
      experimental investigation.
AB  - BACKGROUND: Ureteral endoprostheses are used for dilatation of strictures in
      order to maintain upper urinary tract (UUT) function for a longer period.
      MATERIALS AND METHODS: Three kinds of short (3-4-cm) endoprostheses were inserted
      into the ureter of mongrel dogs with intact UUT or experimental ureter
      strictures. The UUT function was evaluated by means of radiographic examinations
      and in terms of following measures of contractility: intraluminal pressure,
      electroureterography (EUG), and multichannel impedance ureterography (MIUG).
      Studies were performed 1, 3 to 6 months, and 1 to 3 years after prostheses
      implantation. RESULTS: Similar urodynamic changes were registered in
      prosthetically treated ureters of dogs with initially intact UUTs and those with
      ureteral strictures. These disorders consisted of increased UUT intraluminal
      pressure and different functioning of the upper and lower regions of the ureter.
      The bioelectric and contractile activity of the upper UUT regions was reinforced,
      accelerated, and dysrhythmic, while peristaltic ureter wall function below the
      endoprosthesis was rare and weak. CONCLUSIONS: The changes observed are typical
      for ureteral prosthetics. The UUT urodynamic alterations could be attributable
      entirely to the excluding of the ureteral segment from active contraction and
      were the result of the local absence of the ureteral wall closing mechanism. One
      must keep in mind that UUT endoprostheses produce a high load on the ureter wall.
      The transition from UUT hyperfunction to contractile function decompensation may
      depend on the intrinsic compensatory reserves of the ureter.

PMID- 11465336
TI  - Randomized trial of 10 mL and 20 mL of 2% intraurethral lidocaine gel and placebo
      in men undergoing flexible cystoscopy.
AB  - PURPOSE: To determine if 20 mL of 2% intraurethral lidocaine gel is superior to
      10 mL of 2% lidocaine or sterile lubricant for flexible cystoscopy in men.
      PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled trial was
      conducted. Sixty men scheduled to undergo diagnostic flexible cystoscopy were
      randomized to receive either 20 mL of placebo gel (Group I), 10 mL, of 2%
      lidocaine gel (Group II) or 20 mL of 2% lidocaine gel (Group III). A penile clamp
      was applied for 15 minutes to ensure consistent indwelling time in all patients.
      Patients recorded their pain on a 10-cm non-graphical visual analog scale prior
      to cystoscopy as a baseline, during the procedure, and immediately after the
      procedure. Patients also recorded their pain and willingness to have the same
      anesthetic on a 4-point descriptive scale. Heart rate and mean arterial blood
      pressure (MAP) were recorded at specific intervals throughout the procedure, and
      increases in mean arterial pressure were considered objective evidence of patient
      pain. RESULTS: Pain perception was not statistically different in the groups
      (Group I 4.65, Group II 3.93, Group III 3.57; P = 0.406). Pain assessment and
      willingness to have the same anesthetic also did not differ statistically among
      the groups. Similarly, differences in the increases in MAP were not statistically
      significant between groups. CONCLUSION: Instillation of 20 mL or 10 mL of 2%
      lidocaine gel has no advantage over plain lubricant in providing anesthesia for
      flexible cystoscopy in men.

PMID- 11465337
TI  - Modified bulbar urethral sling procedure for the treatment of male sphincteric
      incontinence.
AB  - BACKGROUND AND PURPOSE: Urinary incontinence secondary to intrinsic sphincter
      deficiency is a debilitating condition for the patient and an ordeal for the
      urologist. Because of the complexity of reconstructive surgical techniques and
      the prohibitive cost of the prosthetic devices used, there is a need for a simple
      procedure. We herein report our experience in managing urinary incontinence
      secondary to sphincteric incompetence in nine consecutive patients using a
      modified bulbar urethral sling procedure over a period of 2 years. PATIENTS AND
      METHODS: In eight patients, the incontinence followed open prostatectomy or
      transurethral resection for benign prostatic hyperplasia, and one patient had
      incontinence following fulguration of posterior urethral valves. Our procedure
      uses bolsters that are suspended from the rectus fascia, and a hammock made of a
      folded Dacron patch is placed beneath the bulbospongiosus muscle to form a sling.
      RESULTS: All patients were continent postoperatively, with only mild stress
      leakage in the erect posture, during a mean follow-up of 12.2 months (range 6-22
      months) and required one or two improvised pads per day to remain continent
      during the daytime. Persistent perineal infection necessitated removal of the
      sling in one patient. One patient required clean intermittent catheterization for
      a short period postoperatively. CONCLUSION: This modified bulbar urethral sling
      procedure is a simple yet effective method to treat sphincteric deficiency of any
      cause.

PMID- 11465338
TI  - An introduction to cell migration and invasion.
AB  - This introduction to the current understanding of cell migration and invasion
      indicates how these cellular processes are essential in a variety of
      physiological events, as well as in the pathophysiology of clinical diseases such
      as cancer, cardiovascular disease and preeclampsia. The various molecular
      mechanisms the cells use to migrate and invade are described, and assays
      currently used to investigate these two processes are shown. Finally, clinical
      examples where there is dysregulation of cell migration and invasion are
      presented, namely in the development of cancer, cardiovascular disease and
      preeclampsia.

PMID- 11465339
TI  - Technical aspects of microdialysis of human breast.
AB  - In this study a technique for insertion of microdialysis catheters and the
      influence of the position of the catheters within normal human breast tissue were
      evaluated by measuring amino acids. Moreover, to assess variability over time,
      the levels of amino acids were measured during a period of 3 h. In nine healthy
      women two parallel microdialysis catheters were implanted, guided by a catheter
      for intravenous use, into the breast tissue. All insertions were successful and
      there were no complications. The levels of amino acids were equal in the two
      parallel catheters and varied less than 10% over a period of 3 h. Insertion of
      the microdialysis catheter via an intravenous catheter is suitable for the dense
      breast tissue. The position of the microdialysis catheter within the same breast
      seems to be of minor importance for measurements of amino acids. Thus, the
      described technique is a safe and reproducible way of investigating the human
      breast in vivo.

PMID- 11465340
TI  - Multicentric reference values for some quantities measured with Tina-Quant
      reagents systems and RD/Hitachi analysers.
AB  - Ten clinical laboratories in different regions of Spain have shared the search
      for reference individuals and the production of reference values for quantities
      concerning ferritin, transferrin, rheumatoid factors, C-reactive protein and
      antistreptolysin O, using Tina-Quant reagents systems and RD/Hitachi analysers.
      All the logistic work has been done in co-operation with the supplier of the
      reagents and analysers (Roche Diagnostics Espana, S.L., Barcelona). The reference
      limits produced in the virtual laboratory are derived from the blend of reference
      values obtained by each laboratory. The multicentric reference limits were
      estimated according to the recommendations of the International Federation of
      Clinical Chemistry. The work done is a model of co-operation between the in vitro
      diagnostic industry and clinical laboratories for the production of reference
      values.

PMID- 11465341
TI  - Effects of growth hormone replacement on cortisol metabolism in hypopituitary
      patients treated with cortisone acetate.
AB  - Growth hormone (GH) replacement may inhibit 11beta-hydroxysteroid dehydrogenase
      type 1 (11betaHSD1) activity, resulting in diminished conversion of cortisone to
      cortisol. Moreover, GH replacement may lower bioavailability of hydrocortisone
      tablets. Therefore, substitution therapy with cortisone acetate could be
      disadvantageous during GH replacement. We conducted a randomized, placebo
      controlled GH replacement (1 to 2 U GH/day) study during 6 months, followed by a
      6-month open extension study (2U GH/day). Twelve men and 12 women with GH
      deficiency, of whom 17 received cortisone acetate (25 to 37.5 mg/day),
      participated. Eight patients were randomized to placebo initially. At baseline,
      after 6 and 12 months, urinary cortisol and cortisone metabolites were measured.
      No changes in urinary cortisol metabolites were observed after 6 months placebo
      (n=8). After 6 months GH the urinary
      (tetrahydrocortisol+allotetrahydrocortisol)/tetrahydrocortison ratio
      ((THF+alloTHF)/THE ratio) was unaltered in cortisone acetate treated patients (n
      = 17) and in patients with intact adrenal function (n = 7), whereas after 12
      months GH the (THF + alloTHF)/THE ratio decreased only in cortisone acetate
      treated patients (1 dropout, n=9). Urinary THF and alloTHF were higher in
      cortisone acetate treated patients than in patients with intact adrenal function
      before GH and remained so after 12 months GH (p < 0.05 to p < 0.01). The sum of
      cortisol + cortisone metabolites did not change after GH in either group. The
      urinary free cortisol/free cortisone ratio, presumably reflecting renal
      11betaHSD2 activity, tended to decrease in cortisone acetate treated patients
      (p<0.07 and p<0.05 after 6 and 12 months GH, respectively), as well as in
      patients with intact adrenal function (p<0.05 and a decrease in five/six patients
      after 6 and 12 months GH, respectively). In conclusion, these results suggest
      that GH replacement decreases 11betaHSD1 activity, which becomes manifest in
      patients receiving cortisone acetate substitution therapy. 11betaHSD2 activity is
      unaltered or may even be increased. It is unlikely that the bioavailability of
      conventional doses of cortisone acetate is impaired after GH replacement.

PMID- 11465342
TI  - Neonatal salivary cortisol in response to heelstick: method modifications enable
      analysis of low concentrations and small sample volumes.
AB  - Measuring cortisol in saliva offers important advantages compared to measurement
      in plasma or serum. However, the sampling procedure and also the detection limit
      cause problems, especially in paediatric and neonatal care. We describe a simple
      and efficient sampling procedure, together with a modification of a
      radioimmunoassay, which enables analysis of low (down to 1 nmol/L) concentrations
      of salivary cortisol (10 times lower detection limit than in the original
      procedure). This setting was used in studying salivary cortisol concentrations
      before and after heelstick on healthy newborn infants. A significant rise (median
      81%; p<0.01) in salivary cortisol as response to this invasive stressor was
      noted.

PMID- 11465343
TI  - Surgical organ perfusion method for gene transfer into cells of the
      perifollicular area of the spleen: an experimental trial on farm pigs.
AB  - In an attempt to develop a gene therapy method for splenic and systemic diseases,
      an evaluation was made of surgical methods for gene transfer into porcine spleen.
      We have developed a continuous closed-circuit organ perfusion method for gene
      transfer into porcine spleen. For gene transfer, we used a type-5 replication
      defective adenovirus vector expressing the E. coli beta-galactosidase gene as a
      reporter gene. In eight young 22-35 kg farm pigs, the spleen was perfused in vivo
      with the viral solution via laparotomy, for 30 or 60 min. Gene transfer was
      determined visually on histological cryosections after X-gal and PAS staining.
      Infusion of the viral solution through the splenic artery did not result in gene
      expression. Perfusion of spleen in vivo resulted in beta-galactosidase reporter
      gene expression in the macrophages located around capillaries terminating in the
      perifollicular zone and in the red pulp examined after four days. The present
      results suggest that the surgically performed spleen perfusion method can be used
      for gene transfer in the treatment of diseases having splenic manifestations and
      in systemic diseases.

PMID- 11465344
TI  - Effects of short-term treatment with corticotropin on the serum apolipoprotein
      pattern.
AB  - Treatment with adrenocorticotrophic hormone (ACTH) has a well-documented
      cholesterol-lowering effect. Increased uptake of low-density lipoprotein (LDL) by
      HepG2 cells in response to incubation with ACTH has been demonstrated but the
      precise cholesterol-lowering mechanism has resisted elucidation. Since
      apolipoproteins are important determinants of lipoprotein metabolism, we sought
      to extend the knowledge of the effect of ACTH treatment on the serum
      apolipoprotein (apo) pattern. Twelve healthy individuals and 14
      dyslipoproteinemic hemodialysis patients were recruited. The two groups responded
      similarly to ACTH1-24 at the dose of 1 mg daily for four days. In accordance with
      previous results, serum concentrations of total cholesterol decreased by 18% and
      17%, LDL cholesterol by 25% and 30%, and apo B by 20% and 19%, respectively,
      while there were no significant changes in the serum concentrations of
      triglycerides, high-density lipoprotein cholesterol and apo AI. Novel findings
      were that the serum concentrations of total apo E increased by 48% and 31%, and
      apo B-associated apo E by 69% and 46%, respectively. Moreover, in the healthy
      individuals, the serum concentrations of apo CIII did not change in response to
      ACTH, whereas in the hemodialysis patients, those of apo CIII not associated with
      apo B increased significantly by 44%. Since apo E binds strongly to the LDL
      receptor, the present results suggest that the cholesterol-lowering effect of
      ACTH may be mediated by facilitated hepatic uptake of apo E-enriched apo B
      containing lipoproteins. Thus, the findings stimulate further research.

PMID- 11465345
TI  - Detection by flow cytometry of antibodies against surface and intracellular
      granulocyte antigens.
AB  - A flow cytometric technique was used to detect granulocyte antibodies, with
      attention to the distinction between antibodies directed against surface and
      intracellularly expressed antigens. Ten serum samples with positive results and
      10 with negative results detected by the granulocyte immunofluorescence test
      (GIFT), together with 10 positive serum samples detected by an indirect
      immunofluorescence test (IIF) were analyzed against leukocytes from healthy blood
      donors tested by flow cytometry (FC). Unpermeabilized and permeabilized cells
      were used to allow identification of surface and intracellular binding,
      respectively. The results of testing by GIFT corresponded with those by FC, with
      the exception of the results for four sera: one serum sample was FC negative,
      GIFT positive, and three samples were FC positive, GIFT negative. The IIF
      positive sera were all FC positive, analyzed against permeabilized granulocytes,
      and one serum was also positive against non-permeabilized granulocytes. Analysis
      by FC is a readily performed technique, which can be used for the routine
      detection of antibodies against leukocyte antigens. Screening for granulocyte
      specific antibodies can be carried out with pools of granulocytes from three
      donors. Analysis by FC allows detection of both HLA antibodies and granulocyte
      specific antibodies and by using both unpermeabilized and permeabilized cells,
      antibodies against surface and intracellular antigens, respectively, can be
      identified.

PMID- 11465346
TI  - Plasma levels of von willebrand factor, endothelin-1, prostacyclin and
      thromboxane in children from families with high risk of premature coronary artery
      disease.
AB  - The aim of the study was to assess the plasma levels of endothelial injury
      markers in children from families with high risk of premature coronary heart
      disease (CHD) without other common CHD risk factors (hyperlipidaemia, obesity,
      hypertension, low physical activity). The study comprised 48 children, including
      24 children from high-risk families (HR), according to the NCEP (National
      Cholesterol Education Programme) criteria: one or two parents had clinical
      manifestation of cardiovascular disease before the age of 65 years (mother) or 55
      years (father). The control group included 24 healthy children with no familial
      history of cardiovascular disease. All the children were normolipidaemic
      according to the NCEP and the European Atherosclerosis Society criteria for
      children aged 2-19 years. In the HR group, the concentration of vWf was
      significantly elevated in comparison to that in the control group (p<0.0001).
      Plasma concentrations of ET-1 and TxB2 did not differ significantly between the
      HR group and the controls. Plasma concentrations of the 6-ketoPGF1alpha in the HR
      group and in the respective age and gender HR subgroups were significantly lower
      compared with those of the control group (p<0.00005). Concentration of vWf in the
      HR group was negatively correlated with the concentration of 6-ketoPGF1alpha (r =
      -0.47; p<0.05) and positively correlated with TxB2 (r=0.39; p<0.01). In a
      logistic regression analysis, we found that the 6-ketoPGF1alpha concentration in
      the lower quartile (< 16.1 pmol/L) was associated with a 3.4-fold odds of
      inclusion in the high-risk group versus the upper quartile (>23.0 pmol/L).

PMID- 11465347
TI  - Comparison of eight commercial on-site screening devices for drugs-of-abuse
      testing.
AB  - Eight commercially available on-site drugs-of-abuse testing devices for detecting
      cannabinoids (THC-COOH), opiates (OPI), cocaine (COC), amphetamines (AMP),
      metamphetamines (MET) and benzodiazepines (BZO) were evaluated. The used urine
      specimens suspected of being drug positive were all confirmed by gas
      chromatographic/mass spectrometry (GC/MS). For AMP and MET, sensitivities varied
      between 83 and 95% and specificities between 98 and 100%. Correspondingly,
      sensitivities between 88 and 98% and specificities between 95 and 100% were
      observed for THC-COOH. For BZO, sensitivities varied between 91 and 97% and
      specificities between 97 and 100%. Only a few confirmed positive samples were
      available for OPI and COC, the sensitivities being between 83 and 100% and 100%,
      respectively. On-site devices did not always find extremely high drug
      concentrations. False-negative results were found with AMP in particular.
      Pholcodine, commonly used as medicine, was observed to give false-positive
      results with most of the devices and was not, however, included in given cross
      reactivity tables. It was found that the devices differed markedly with respect
      to interpretation of test results and to ease of test performance, leading to the
      suggestion that different criteria for selecting on-site devices for either
      emergency laboratories in hospitals or for police stations and prisons should be
      used. Since the overall specificity of any of the devices was not 100% and false
      positives were identified, we found it important to confirm any positive
      screening test result.

PMID- 11465348
TI  - Cystatin C levels in sera of patients with acute infectious diseases with high C
      reactive protein levels.

PMID- 11465349
TI  - Genotype x environment interactions in milk yield and quality in Angus, Brahman,
      and reciprocal-cross cows on different forage systems.
AB  - Milk yield and quality were observed on 93 Angus, Brahman, and reciprocal-cross
      cows over 3 yr to evaluate the interactions of direct and maternal breed effects
      and heterosis with forage environment. Forage environments were common
      bermudagrass (BG), endophyte-infected tall fescue (E+), and a rotational system
      (ROT) of both forages, in which each forage (BG or E+) was grazed during its
      appropriate season, usually June through October for BG and November through May
      for E+. Milk yield was estimated each of 6 mo (April through September) via
      milking machine and converted to a 24-h basis. Milk fat, milk protein, and
      somatic cell count were analyzed by a commercial laboratory. Heterosis for milk
      yield was similar among forages, averaging 2.4 kg (P < 0.01). Expressed as
      percentages of purebred means, heterosis for milk yield was largest on E+
      (52.8%), intermediate on ROT (39.3%), and smallest on BG (23.7%). Direct breed
      effects for milk yield favored Brahman, and they were similar among forages but
      tended to be larger for E+ (2.5 kg) and ROT (2.8 kg) than for BG (1.3 kg). Direct
      breed effects for milk fat favored Brahman and were similar among forages but
      tended to be larger for E+ (1.0%) and ROT (1.0%) than for BG (0.6%). Purebred
      cows exceeded crossbreds in milk protein by 0.1% on ROT (P < 0.10). Crossbred
      cows had lower somatic cell counts than purebreds on BG (P < 0.05), E+ (P <
      0.01), or ROT (P > 0.30). Heterosis for somatic cell counts as percentages of
      purebred means was similar for BG (-68.3%) and E+ (-68.9%) and less favorable for
      ROT (-31.6%). Maternal breed effects for somatic cell count favored Angus on ROT
      (P < 0.10) with a similar nonsignificant trend on BG and E+. Direct breed effects
      for somatic cell count favored Brahman on ROT (P < 0.10) with similar
      nonsignificant trends on BG and E+. These results suggested that a rotation of
      cows from E+ to BG in the summer can partially alleviate negative effects of E+
      on milk yield. Conclusions also indicated an advantage to crossbred cows in
      somatic cell count and provided evidence of both direct and maternal breed
      effects for this trait. The results also suggested that direct breed effects for
      milk yield, milk fat, and somatic cell count and heterosis for milk yield and
      somatic cell count (as percentages of purebred means) tended to vary with forage
      environment, indicating a potential for genotype x environment interaction for
      these traits.

PMID- 11465350
TI  - Effects of inorganic and organic copper supplemented to first-calf cows on cow
      reproduction and calf health and performance.
AB  - Two experiments were conducted to determine whether the supplementation of Cu in
      the organic or inorganic form to 2-yr-old cows, before and after calving, affects
      reproduction rate, calf health and performance, passive transfer of
      immunoglobulin, or liver and serum Cu concentrations compared with unsupplemented
      controls. Cows (n = 75 in 1997; n = 120 in 1998) were randomly assigned by
      estimated calving date and body condition score to one of three treatments: 1)
      Control, control; 2) Inorganic, inorganic Cu supplement (200 mg Cu from CuSO4);
      3) Organic, organic Cu supplement (100 mg Cu from AvailaCu). In 1998, a fourth
      treatment was added; 4) CU-ZN, organic Cu and Zn (400 mg Zn from AvailaZn in the
      Organic diet). Cows were fed a hay-based diet and individually fed supplements
      for approximately 45 d before and 60 d after calving (approximately January 15 to
      May 15 each year). Liver biopsies were obtained from cows before supplementation
      began, and from cows and calves at 10 and 30 d after calving. Blood samples were
      obtained from both cows and calves at calving, and colostrum samples were
      collected for IgG and mineral content. Cow liver Cu concentrations before
      supplementation began were 58 mg/kg in 1997 and 40 mg/kg (DM basis) in 1998. By
      10 d after calving, liver Cu concentrations of Control cows had decreased (P <
      0.05) to 24 mg/kg (Cu deficient) in both years, whereas liver Cu concentrations
      of Cu-supplemented cows increased (P < 0.05) in both years. Calf liver Cu
      concentrations at 10 d of age were similar (P > 0.10) for all treatment groups.
      No differences (P > 0.10) were found in colostrum Cu concentrations, or in calf
      health among treatments. No differences (P > 0.10) were found in cow BW change,
      calf serum Cu concentrations, calf weaning weights, or in cow 60-d pregnancy
      rates among treatments in either year. In 1998, cows in the Organic group had
      higher (P < 0.05) 30-d pregnancy rate than Control cows. Neither serum samples
      nor placental tissue were reliable indicators of Cu status in cows. Feeding
      supplemental Cu (either inorganic, organic, or organic with extra Zn) to cows
      with liver Cu concentrations of approximately 50 mg/kg before calving did not
      improve cow 60-d pregnancy rates or the health and performance of their calves
      when compared with unsupplemented cows.

PMID- 11465351
TI  - Early weaning and postweaning nutritional management affect feedlot performance
      of angus x simmental heifers and the relationship of 12th rib fat and marbling
      score to feed efficiency.
AB  - Early-weaned Angus x Simmental heifers were used to evaluate the effects of
      postweaning nutritional management on feedlot performance, carcass merit, and the
      relationship of intramuscular and subcutaneous fat deposition to the feed
      efficiency among heifers fed for a high-quality market. Sixteen heifers were
      weaned at 73+/-5.5 d of age and grazed on endophyte-infected tall fescue for 18
      mo before entering the feedlot (early-weaned-P). Eighty heifers from the
      following year's calf crop were weaned at 71+/-5.5 d of age and allowed either ad
      libitum access to a 25% concentrate diet (early-weaned-25C) or limit-fed a 90%
      concentrate diet (early-weaned-90C) to achieve a similar ADG. Following a 119-d
      growing period, 16 early-weaned-90C and 16 early-weaned-25C calves were paired
      based on BW and growth rate and individually fed during the finishing period
      along with the early-weaned-P heifers. Ultrasound measurements of s.c. and i.m.
      fat were recorded at approximately 60-d intervals throughout the finishing
      period. Feed efficiency was regressed against s.c. and i.m. fat, and i.m. fat was
      regressed on s.c. fat. Despite a similar ADG, early-weaned-90C calves gained more
      efficiently (P < or = 0.05) in the feedlot than early-weaned-25C calves. Heifers
      finished as yearlings tended (P < or = 0.10) to gain faster but gained less
      efficiently (P < or = 0.01) than early-weaned-90C heifers finished as calves. The
      rate of s.c. and i.m. fat deposition was similar between early-weaned-90C and
      early-weaned-25C heifer calves. The calves were grouped together for comparison
      to yearlings. Feed efficiency decreased quadratically (P < or = 0.01) as s.c. fat
      cover increased. The rate at which feed efficiency decreased relative to
      increasing s.c. fat cover was similar regardless of age at feedlot entry.
      However, heifers finished as calves gained more efficiently (P < or = 0.01) than
      yearlings at any given fat thickness. Feed efficiency decreased linearly (P < or
      = 0.01) as i.m. fat increased among heifers finished as calves. Additionally,
      heifers finished as calves deposited i.m. fat at a faster rate relative to s.c.
      fat (P < or = 0.01) than yearlings. These data suggest that heifers finished as
      calves produce high-quality carcasses with less s.c. fat cover while gaining more
      efficiently than heifers finished as yearlings.

PMID- 11465352
TI  - Fiber characteristics of qiviut and guard hair from wild muskoxen (Ovibos
      moschatus).
AB  - In response to increasing commercial interest and the high market value of qiviut
      (the downy underwool of the muskox), we have employed standards and measurements
      used in the wool and cashmere industries to describe qiviut fiber
      characteristics. Fleece samples (qiviut with guard hair) were shaved from the
      midshoulder of 299 wild muskox hides of known sex and age (1, 2, 3, and 4+ yr)
      during the Banks Island, Canada, muskox harvest in November 1997. Samples were
      analyzed for fiber diameter distribution of raw fiber and qiviut, scoured and
      qiviut yields, and lengths of guard hair and qiviut fiber. We found a sex x age
      interaction for average fiber diameter (AFD) in raw fiber (P= 0.002) and qiviut
      (P < 0.001) only. Adult males had significantly coarser AFD than females (21.5
      microm, males vs 20.1 microm, females and 18.2 microm, males vs 17.5 microm,
      females) for raw fiber and qiviut, respectively. Qiviut AFD from yearlings was
      1.7 microm finer than the AFD of adult qiviut. Fiber diameter distribution (SD)
      decreased with age in the raw sample (P < 0.003) and qiviut (P < 0.001) and
      qiviut SD was greater (P < 0.001) in males than in females. Qiviut theoretical
      yield (% mass of fibers < or = 30 microm) increased (P < 0.001) with age, and
      females had higher theoretical yields than males (P < 0.001). Scoured yield did
      not vary between sexes in any age class and averaged 93.3%. Qiviut staple length
      did not differ with either age or sex. In summary, differences between the sexes
      were small up to the 3rd yr, and these differences were not likely to be of
      commercial importance. However, considering that AFD is a primary commercial
      criterion of value, AFD changes from 16.5 microm in yearlings to 18.2 microm in
      adults and from 17.5 microm in adult females to 18.2 microm in adult males would
      be expected to result in significant differences in commercial value.

PMID- 11465353
TI  - Effect of GnRH pretreatment on reproductive performance of postpartum suckled
      beef cows following synchronization of estrus using GnRH and PGF2alpha.
AB  - The effect of GnRH pretreatment on estrus detection rate, precision of estrus,
      and reproductive performance of postpartum beef cows synchronized to estrus using
      GnRH and PGF2alpha was evaluated. In Exp. 1, Angus cows (n = 87) were randomly
      assigned by parity, postpartum interval, and body condition score (BCS) to
      receive either 1) GnRH on d -7 and PGF2alpha on d 0 (GP) or 2) the GP treatment
      and an additional injection of GnRH on d -16 (GGP). Estrus detection and AI were
      conducted twice daily from d -3 to d 3. At 72 h after PGF2alpha, all animals not
      previously detected in estrus were bred by AI and received a concurrent injection
      of GnRH (TAI). Synchronized pregnancy rates were numerically increased (P = 0.15)
      in cows treated with GGP (55%) compared with those on the GP treatment (44%). In
      Exp. 2, 1,276 spring-calving, suckled beef cows in nine herds were randomized to
      treatments as described for Exp. 1, except that the initial GnRH injection for
      the GGP treatment was administered on d -14. Herd affected all indicators of
      reproductive performance (P < 0.05). The percentage of animals detected in estrus
      prematurely (d -3 to d 0; 7%) was not affected by treatment. Estrus response rate
      was influenced by postpartum interval (< 60 vs > or = 60; 61 vs 73%; P < 0.01)
      and a three-way interaction of parity, BCS, and treatment (P < 0.01). Within
      animals with a BCS > or = 5.5, the GGP treatment tended to increase the detection
      of estrus in primiparous cows (GP vs GGP; 76 vs 91%; P = 0.11) and decrease
      detection in multiparous cows (GP vs GGP; 78 vs 72%; P < 0.10). However, because
      conception rate to TAI in animals with a BCS > or = 5.5 was greater (P < 0.05) in
      the GGP than in the GP group (28 vs 8%, respectively), this interaction was
      interpreted to represent a shift in interval to estrus induced by the GGP
      treatment, rather than a reduction in the synchronization of ovarian function.
      Conception rates of animals inseminated to an observed estrus did not differ
      among treatments (P = 0.15). Synchronized pregnancy rate tended (P = 0.06) to be
      greater in GGP- (53%) than in GP-treated animals (47%). In conclusion,
      pretreatment with GnRH tended to increase pregnancy rates during a 6-d
      synchronization period, primarily through enhanced conception rates of cows bred
      by TAI. In contrast to our hypothesis, GnRH pretreatment did not increase the
      percentage of animals detected in estrus or the precision of estrus expression.

PMID- 11465354
TI  - A comparison of the USDA ossification-based maturity system to a system based on
      dentition.
AB  - Two studies using commercially fed cattle were conducted to determine the
      relationship of the USDA bone ossification-based maturity system to one based on
      the number of permanent incisors present at slaughter. These studies showed that
      91.5 to 100% of cattle with zero permanent incisors (< 23.8 mo of age), 89.1 to
      97.5% of cattle with two permanent incisors (23.8 to 30.4 mo of age), 75 to 82.2%
      of cattle with four permanent incisors (30.4 to 38.0 mo of age), 64 to 72.5% of
      cattle with six permanent incisors (38.0 to 45.3 mo of age), and 40% of cattle
      with eight permanent incisors (> 45.3 mo of age) were graded as A maturity by the
      USDA maturity classification system. Kappa tests revealed no statistical
      relationship between the dentition- and skeletal ossification-based maturity
      systems. Dentition-based maturity agreed with ossification/lean maturity for only
      162 of 1,264 carcasses in Exp. 1 and only 54 of 200 carcasses in Exp. 2. Cattle
      with two, four, six, or eight permanent incisors were classified in more youthful
      categories of USDA bone ossification/lean maturity than they should have been.
      Male cattle were more likely to be misclassified into a younger age category by
      the USDA system than were female cattle. It seems that determining physiological
      maturity by number of permanent incisors rather than by the current USDA method
      of subjectively evaluating skeletal and lean maturity may prove to be a more
      accurate technique of sorting beef carcasses into less-variable age groups.

PMID- 11465355
TI  - Ovulation rate and litter size in gilts immunized against androstenedione and
      17alpha-hydroxyprogesterone.
AB  - Two experiments were conducted to evaluate the effects of the immunization of
      gilts against ovarian steroids on ovulation rate and litter size. In Exp. 1,
      gilts (n = five gilts/treatment) at 165+/-1.6 d of age were immunized against
      either carrier (Control), androstenedione, or 17alpha-hydroxyprogesterone. Age at
      puberty and estrous cycle length averaged 208+/-5.5 (P = 0.67) and 20.3+/-2.8 d
      (P = 0.41), respectively, and were not affected by treatment. The androstenedione
      and 17alpha-hydroxyprogesterone immunized gilts had higher (P < 0.02) ovulation
      rates than Controls (14.2, 14.2, and 11.4+/-0.8, respectively). Total pigs born
      (P = 0.66) and pigs born live (P = 0.65) for the androstenedione-treated group
      were not different from Controls. Gestation length was not different (P = 0.36)
      between any of the treatments and the Controls (115+/-0.9 d). Procedures used in
      Exp. 2 were similar to those in Exp. 1, except that only Control (n= 18) and
      17alpha-hydroxyprogesterone (n = 16) treatments were included and only litter
      size at farrowing was measured. Total pigs and pigs born live were higher in the
      17a-hydroxyprogesterone-treated gilts than in the Controls (12.6 vs 10.5+/-0.6, P
      < 0.02; and 11.4 vs 9.2+/-0.6; P < 0.01, respectively). Data from this study
      indicate that litter size in gilts can be increased by immunization against
      17alpha-hydroxyprogesterone.

PMID- 11465356
TI  - A comparison of native tallgrass prairie and plains bluestem forage systems for
      cow-calf production in the southern great plains.
AB  - The objective of this study was to compare an introduced warm-season perennial
      grass (plains bluestem, Bothriochloa ischaemum) to native tallgrass prairie for
      cow-calf production. Three systems were used, two based on tallgrass prairie with
      two different forms of protein supplementation and one based on plains bluestem
      as the primary forage. The systems were as follows: 1) native tallgrass prairie
      with pelleted oilseed meal as the winter protein supplement (native-control); 2)
      native tallgrass prairie with limited access to wheat pasture as the winter
      protein supplement (native-wheat); and 3) plains bluestem with limited access to
      wheat pasture as the protein supplement (bluestem-wheat). Oilseed meal protein
      supplements were fed twice weekly. Cows grazing wheat pasture were allowed 6 h of
      grazing twice weekly. Ninety-nine cows per year were used over the 3-yr study.
      Cows were sired by either Charolais, Gelbvieh, Angus, or Hereford bulls out of
      commercial Angus-Hereford dams. Calves were sired by Simmental bulls. Calving and
      weaning rate increased over time but did not differ among systems or breed types.
      System did not influence the size or body condition score of cows or the
      performance of calves, but changes in the weight and condition scores of cows
      were greater on either native system than on the bluestem-wheat system. Cows from
      Charolais and Gelbvieh bulls were taller (P < 0.05), and heavier (P < 0.05), and
      weaned heavier (P < 0.05) calves than cows from Angus or Hereford bulls. The
      weight of cows on the bluestem-wheat system tended to decrease over time, whereas
      cows grazing on the native systems tended to gain weight over time. The native
      control system was the most profitable system based on cow production. If excess
      hay produced from the bluestem-wheat system was sold as a cash crop, then this
      system was the most profitable. In general, we conclude that limit-grazing wheat
      pasture is a viable alternative to oilseed meal as protein supplement for
      wintering dry cows. Although the bluestem system had 2.5 times the carrying
      capacity of the native prairie systems, increased productivity was offset by
      increased production costs. All systems were equal on a cow basis for providing
      nutrients for the cow-calf production system.

PMID- 11465357
TI  - Assessment of genetic variability of resistance to gastrointestinal nematode
      parasites in Creole goats in the humid tropics.
AB  - Goat production is widespread in the tropics. Goats are very susceptible to
      gastrointestinal nematode infection, but there is less evidence of their genetic
      resistance. Genetic resistance of Creole goats to gastrointestinal nematodes has
      been studied at Guadeloupe in the French West Indies since 1995. The objective of
      this research was to investigate genetic variation for resistance to
      gastrointestinal nematode infection, in order to introduce this trait into
      breeding schemes. Genetic variability was assessed within a Creole experimental
      flock. Forty-nine sire groups were characterized at weaning and 55 during
      fattening after weaning. Kids were naturally infected, mainly by Haemonchus
      contortus and Trichostrongylus colubriformis. Fecal egg counts were determined
      once at weaning and every 6 and 7 wk after drenching during fattening. Blood
      samples were collected every 7 wk during fattening for determination of packed
      cell volume. Live weights were recorded at weaning and at the beginning and
      middle of every infection period during fattening. Genetic parameters were
      estimated using the REML for multivariate animal models. The heritability
      estimate for transformed fecal egg count was 0.37+/-0.06 at weaning. During
      fattening, it increased from 0.14+/-0.05 at 4 mo to 0.33+/-0.06 at 10 mo.
      Heritabilities of packed cell volume ranged from 0.10 to 0.33. At weaning,
      maternal heritability of fecal egg count reached 0.26 and direct heritability
      0.20. After 6 mo of age, maternal effects were found to be unimportant for fecal
      egg count and packed cell volume. Live weights presented significant genetic
      variability. Genetic relationships between fecal egg counts and live weight in
      infected pastures were never significant. Genetic correlations between packed
      cell volume and live weight decreased from 0.47 to 0.10 from weaning to 10 mo of
      age. These results demonstrated the feasibility of breeding for improved
      resistance to nematodes in Creole kids.

PMID- 11465358
TI  - Direct and maternal genetic effects on birth and weaning traits in multibreed
      cattle data and predicted performance of breed crosses.
AB  - Direct and maternal additive effects and heterosis were estimated using data from
      straightbred Angus, Brahman, Charolais, Hereford, and four generations of
      rotational crosses among these breeds. Traits of interest were birth weight,
      Julian day of birth, average daily gain from birth to weaning, 205-d weight, and
      weaning weight per cow exposed. Complete data were available on 3,445 calves
      produced from 4,733 matings. Discrete generations of 4-yr duration were produced
      from 1970 through 1988. Brahman was included in each rotational crossbreeding
      system. Genetic effects were estimated by regression. Direct and maternal
      additive effects of Brahman, Charolais, and Hereford were estimated as deviations
      from Angus. Direct and maternal heterosis effects were assumed proportional to
      expected heterozygosity. The Brahman direct additive effect resulted in later
      born calves (P < 0.01). Brahman, Charolais, and Hereford direct additive effects
      increased birth weight, and the Brahman maternal additive effect decreased birth
      weight compared with Angus (P < 0.05). Charolais direct and maternal additive
      effects were greater than Angus for average daily gain and 205-d weight (P <
      0.01). The Hereford maternal additive effects on average daily gain and 205-d
      weight were less than those of the other breeds (P < 0.01). Breed combinations
      including Brahman had greater direct heterosis for birth weight, average daily
      gain, and 205-d weight than other combinations (P < 0.01). Angus, Charolais, and
      Hereford direct additive effects on weaning weight per cow exposed were greater
      than Brahman (P < 0.05). Predicted average daily gain, 205-d weight, and weaning
      weight per cow exposed were, on average, greater in four-breed rotation systems
      than in three- and two-breed systems. Among two-breed rotation systems, predicted
      average daily gain and 205-d weaning weight were greatest for Charolais-Brahman
      and least for Angus-Hereford. Calves from the Angus-Charolais-Hereford system
      weighed less at weaning than any other three-breed combination. However, weaning
      weight per cow exposed from the Angus-Charolais-Hereford system was greatest
      among three-breed systems. Within three- and four-breed rotation systems, ranges
      in predicted birth and weaning weights among generations varied by up to 10.0 and
      25.2 kg, respectively. The choice of breeds affects performance, and the sequence
      of their use may affect intergenerational variation in performance.

PMID- 11465359
TI  - Disease-induced variability of genetic correlations: ascites in broilers as a
      case study.
AB  - Breeding against a production disease is complicated by multiple relationships
      between productivity, disease, and environment. Ascites in broilers is such a
      disease. The combination of the reasonably well understood etiology (a
      physiological/pathological cascade due to inadequate oxygen supply) and the
      practical relevance makes ascites a relevant case for demonstrating and partly
      revealing these complex relationships. Chickens (n = 2,788) were tested in an
      ascites-challenging (cold) environment. Genetic analysis of mortality and
      pathology in combination with performance and physiological traits (especially
      blood gas traits) revealed ample opportunities for selection against ascites
      expression. The genetic correlation structure indicated that different mortality
      traits and pathology traits roughly represent one common characteristic. Direct
      selection against pathology is more effective than selection on the basis of
      growth or blood gas traits. The observed negative correlation (-0.26) between
      productivity and ascites was unexpected. From the etiology of ascites (inadequate
      supply of oxygen relative to the demand), a positive (unfavorable) correlation
      was expected. To demonstrate that the actual disease occurrence caused this
      apparent contradiction, the data from the undiseased subpopulation were
      reanalyzed. In the undiseased subpopulation, the genetic correlation between
      productivity and ascites was positive (0.29). This discrepancy was confirmed by
      comparing regression of ascites expression on actual performance with regression
      of ascites on independently assessed performance breeding values. The lability of
      the genetic correlation was explained from complex interactions between
      productivity, disease susceptibility, and actual occurrence of the disease. The
      revealed mechanism can be generalized to other production-related diseases and
      results in systematically lower genetic correlations between disease and
      productivity. It was inferred that genetic correlations between productivity and
      such diseases will always be prone to the demonstrated environmental sensitivity,
      which complicates index selection against production-related diseases.

PMID- 11465360
TI  - Segregation ratios and growth rate in inactive ovine metallothionein 1a-ovine
      growth hormone transgenic mice.
AB  - Objectives were to determine whether the oMt1a-oGH transgene shows normal
      Mendelian segregation and whether oMt1a-oGH mice exhibit normal growth without
      the zinc supplementation required to increase plasma oGH levels and stimulate
      growth. Transgenic mice were reciprocally backcrossed for four generations to
      high growth and control lines to form lines GM and GR, respectively. In the fifth
      generation, hemizygous transgenic mice (T/-) were crossed within each line.
      Pooled across backcross generations, there was a deficit (P < 0.001) of T/-
      progeny in lines GM (31.6%) and GR (22.2%) compared with expected (50%). In the
      T/- x T/- cross, the combined percentage of homozygous (T/T) and hemizygous
      transgenic mice was less (P < 0.001) than expected (75%) in both GM (44.2%) and
      GR (38.5%). Backcross T/- mice had lower (P < 0.05) 3-wk BW and lower (P < 0.001)
      6-wk BW and 3- to 6-wk postweaning gains than nontransgenic mice. Similar
      genotypic differences were found in the T/- x T/- cross. No significant growth
      differences were found between T/T and T/- progeny. Using segregation ratios from
      the T/- x T/- mating, the relative fitness estimates of T/T, T/-, and -/-
      (nontransgenic) mice were 0.345, 0.223, and 1.0, respectively, in line GM and
      0.218, 0.205, and 1.0 in line GR. Fitness estimates in the back-cross for T/- and
      -/- were 0.463 and 1.0 in line GM and 0.285 and 1.0 in line GR. Abnormal
      segregation ratios may be due to germline mosaicism or reduced fitness due to
      differential embryo survival. Reduced growth of oMt1a-oGH transgenic mice when
      the transgene is switched off suggests a subtle developmental abnormality, which
      may contribute to a reduction in fitness.

PMID- 11465361
TI  - Genetics of milk yield and fertility traits in Holstein-Friesian cattle on large
      scale Kenyan farms.
AB  - Purebred Holstein-Friesian cows are the main exotic breed used for milk
      production on large, medium, and small farms in Kenya. A study was undertaken on
      seven large-scale farms to investigate the genetic trends for milk production and
      fertility traits between 1986 and 1997 and the genetic relationships between the
      traits. This involved 3,185 records from 1,614 cows, the daughters of 253 sires.
      There was a positive trend in breeding value for 305-d milk yield of 12.9 kg/ yr
      and a drop in calving interval of 0.9 d/yr over the 11-yr period. Bulls from the
      United States (U.S.) had an average total milk yield breeding value 230 kg higher
      than the mean of all bulls used; Canada (+121 kg), Holland (+15 kg), the United
      Kingdom (U.K., 0 kg), and Kenya (-71 kg) were the other major suppliers of bulls.
      Average breeding values of bulls for calving interval by country of origin were 
      1.31 (Canada), -1.27 (Holland), -0.83 (U.S.), -0.63 (Kenya), and 0.68 d (U.K.).
      The genetic parameters for 305-d milk yield were 0.29 (heritability), 0.05
      (permanent environment effect as proportion of phenotypic variance) resulting in
      an estimated repeatability of 0.34. Using complete lactation data rather than 305
      d milk yield resulted in similar estimates of the genetic parameters. However,
      when lactation length was used as a covariate heritability was reduced to 0.25
      and the permanent environment effect proportion increased to 0.09. There was
      little genetic control of either lactation length (heritability, 0.09) or calving
      interval (heritability, 0.05); however, there were strong genetic correlations
      between first lactation milk yield, calving interval, and age at first calving.

PMID- 11465362
TI  - Characterization of topcross progenies from Hereford, Limousin, and Piedmontese
      sires.
AB  - Breeds of larger mature size tend to grow more rapidly and be older when
      attaining a given level of fatness. Hereford, Limousin, and Piedmontese are of
      approximately equal mature size and yet may vary in body composition at a given
      degree of maturity. However, direct comparisons among these three breeds were not
      found. Therefore, the objective of this research was to compare Hereford,
      Limousin, and Piedmontese progenies for economically important traits. Crossbred
      cows were bred to Hereford (n = 23), Limousin (n = 24), or Piedmontese (n = 24)
      sires. Male calves were either left intact or castrated at approximately 2 mo of
      age. Calves remained with their dams until weaning at an average age of 179 d.
      Male calves were then individually fed a growing ration until they reached 386 kg
      and then fed a finishing ration either 90 or 132 d. They were then slaughtered at
      a commercial abattoir and carcass data were collected. Female calves were group
      fed and used to examine nutritional effects on age at puberty. Data were analyzed
      using REML and linear contrasts among the breed-of-sire effects evaluated.
      Herefordsired calves had shorter gestation periods and weighed less at birth than
      either Limousin- or Piedmontese-sired calves. Calving difficulty of Hereford- and
      Limousin-sired calves was less than that of Piedmontese-sired calves. Limousin
      sired calves tended to grow more rapidly than Hereford-sired calves. By the
      finishing phase, Limousin- and Hereford-sired calves had greater average daily
      gains than Piedmontese-sired calves. Differences in dry matter intake among
      breeds of sire were relatively small. Differences in carcass weight, longissimus
      muscle area, fat depth, and percentage kidney, pelvic, and heart fat resulted in
      a clear stratification of USDA yield grade between breeds of sire. Differences in
      percentage primal cuts were similar to those for USDA yield grade. Hereford-sired
      calves had more marbling than progeny of Limousin or Piedmontese sires. However,
      the force necessary to shear cores from steaks of Piedmontese-sired calves was
      less than for progeny of Limousin or Hereford sires. Hereford- and Piedmontese
      sired heifers were younger at puberty than Limousin-sired heifers. Within breeds
      of similar mature size and growth rate, ample variation exists in age at puberty
      and body composition at an approximately equal degree of maturity.

PMID- 11465363
TI  - Association of a genetic marker with blood serum insulin-like growth factor-I
      concentration and growth traits in Angus cattle.
AB  - The objective of this research was to evaluate a biallelic genetic marker
      identified in the first promoter region of the bovine IGF-I gene. The point
      mutation was identified as a T-to-C transition by sequencing the polymorphic
      fragments. A PCR-RFLP procedure was developed for determining the marker
      genotypes. Marker genotypes were determined for 760 Angus calves from divergent
      lines that were created by selection for high or low serum IGF-I concentration
      (allele A: 63.9%, B: 36.1%). Data were analyzed using the multiple-trait
      derivative-free restricted maximum likelihood computer programs with animal
      models. The full animal model included fixed effects of marker genotype, birth
      year, season of birth, sex, age of dam, and selection line; random effects of
      animal, maternal genetic, and maternal permanent environmental effects; and a
      covariate for age of calf. Traits analyzed included blood serum IGF-I
      concentrations on d 28, 42, and 56 of the postweaning test, mean IGF-I
      concentration, birth weight, weaning weight, on-test weight, off-test weight, off
      test hip height, postweaning gain, and weight gain during the 20-d period
      immediately after weaning. Results from the analysis across selection lines
      showed a significant association of the BB genotype with higher weight gain
      during the first 20 d after weaning and a slight dominance effect of the marker
      on postweaning gain. Analysis within the low IGF-I line also showed a significant
      association of the BB genotype with higher weight gain during the first 20 d
      after weaning and with on-test weight, although analysis within the high IGF-I
      line did not show any significant association. The associated effects of the
      marker need to be verified in other cattle populations.

PMID- 11465364
TI  - Transgenesis may affect farm animal welfare: a case for systematic risk
      assessment.
AB  - This paper considers (potentially) harmful consequences of transgenesis for farm
      animal welfare and examines the strategy of studying health and welfare of
      transgenic farm animals. Evidence is discussed showing that treatments imposed in
      the context of farm animal transgenesis are by no means biologically neutral and
      may compromise animal health and welfare. Factors posing a risk for the welfare
      of transgenic farm animals include integration of a transgene within an
      endogenous gene with possible loss of host gene function (insertional mutations),
      inappropriate transgene expression and exposure of the host to biologically
      active transgene-derived proteins, and in vitro reproductive technologies
      employed in the process of generating transgenic farm animals that may result in
      an increased incidence of difficult parturition and fetal and neonatal losses and
      the development of unusually large or otherwise abnormal offspring (large
      offspring syndrome). Critical components of a scheme for evaluating welfare of
      transgenic farm animals are identified, related to specific characteristics of
      transgenic animals and to factors that may interact with the effects of
      transgenesis. The feasibility of an evaluation of welfare of transgenic farm
      animals in practice is addressed against the background of the objectives and
      conditions of three successive stages in a long-term transgenic program. Concrete
      steps with regard to breeding and testing of transgenic farm animals are
      presented, considering three technologies to generate transgenic founders:
      microinjection, electroporation and nuclear transfer, and gene targeting
      including gene knockout. The proposed steps allow for unbiased estimations of the
      essential treatment effects, including hemi- and homozygous transgene effects as
      well as effects of in vitro reproductive technologies. It is suggested that the
      implementation of appropriate breeding and testing procedures should be
      accompanied by the use of a comprehensive welfare protocol, specifying which
      parameters to monitor, at which stages of the life of a farm animal, and in how
      many animals. Some prerequisites and ideas for such a protocol are given. It is
      anticipated that systematic research into the welfare of farm animals involved in
      transgenesis will facilitate the use of the safest experimental protocols as well
      as the selection and propagation of the healthiest animals and, thereby, enable
      technological progress that could be ethically justified.

PMID- 11465365
TI  - Thermoregulatory ability of beef heifers following intake of endophyte-infected
      tall fescue during controlled heat challenge.
AB  - Consumption of endophyte-infected tall fescue during summer months can result in
      severe hyperthermia in cattle. Six heifers (296+/-8.3 kg BW) were used to
      determine changes in body temperature control that occur with consumption of an
      endophyte-infected tall fescue diet during controlled heat challenge. All animals
      were exposed in five separate periods to a step increase in ambient temperature
      (Ta) from 21 to 31 degrees C while fed E+ (5 microg ergovaline x kg(-1) x d(-1))
      or endophyte-free (E-) diets. Core body temperature (Tcore) was monitored
      continuously using implanted, telemetric temperature transmitters. Heat
      production and heat loss were also measured at selected times to identify primary
      effects of E+ on thermal balance. Pretreatment Tcore exhibited a diurnal rhythm
      at a constant Ta of 21 degrees C, with high and low values at 2300 and 1300,
      respectively. An increase in daily averaged Tcore (P < 0.001) occurred with an
      increase in Ta from 21 to 31 degrees C. Likewise, all phases of the daily cycle
      increased equally during this challenge. This increase at 31 degrees C was
      associated with higher levels of respiration rate, skin temperature, respiratory
      vaporization, and skin vaporization (P < 0.05) and lower blood levels of
      thyroxine (P < 0.05). Intake of the E+ diet further elevated Tcore in heifers
      during the short-term heat challenge (2 d), and the effect was most pronounced at
      0000 to 0300 and declined thereafter. The increase in Tcore during E+ treatment
      was associated with an increase in respiration rate (P < 0.05), whereas metabolic
      heat production, skin temperature, skin vaporization and respiratory vaporization
      were unaffected. These results show that consumption of an E+ diet during
      continuous heat challenge results in a marked increase in core body temperature,
      especially during nighttime exposure to heat stress, due primarily to a reduction
      in cutaneous heat transfer, with no effect on heat production or other measured
      avenues of heat loss.

PMID- 11465366
TI  - Effects of exogenous somatotropin during early gestation on maternal performance,
      fetal growth, and compositional traits in pigs.
AB  - The objective of this study was to determine the effects of maternal treatment
      with porcine somatotropin (pST) during early gestation on embryonic survival,
      fetal development, and internal environment for fetal growth. Sixty-two crossbred
      gilts received daily injections of either 3 mL of a placebo (control, n = 31) or
      6 mg of pST (n = 31) from d 10 to 27 of gestation. Representative gilts were
      slaughtered on d 28, 37, and 62 of gestation. The remaining gilts were allowed to
      farrow. It was found that embryonic survival was not influenced by pST treatment
      (P > 0.10). However, pST affected the growth and composition of the maternal
      (endometrium) and fetal (chorion) parts of the placenta. Thus, endometrial RNA
      concentration tended to be increased by pST at d 37 (P = 0.15), and it was
      increased at d 62 (P < 0.05) of gestation, which is indicative of increased
      capacity for protein synthesis. At birth, placental chorion weight (P < 0.10) and
      contents of DM and protein (P < 0.05) were increased due to pST treatment, but no
      effects were detectable up to d 62 of gestation. Maternal pST treatment was
      effective at increasing nutrient supply to the embryo as suggested from elevated
      glucose concentrations in amniotic and allantoic fluids (P < 0.05) at d 28 of
      gestation. With regard to prenatal growth, embryonic DNA concentration was
      slightly elevated at d 28 (P < 0.10), but pST did not induce any changes in
      average embryonic, fetal, or neonatal weights. However, within litters, the birth
      weights of piglets in the 25% lowest weight group (LW) were increased by pST
      treatment vs control LW pigs (1,241+/-55 vs 1,099+/-59 g, P < 0.10). Thirty-eight
      neonates from 15 litters divided among the three weight groups were examined for
      body composition. The weight of the intestinal tract was increased above average
      after maternal pST treatment (P < 0.01). Additionally, the amounts of tissues
      such as bone (P = 0.12) and s.c. fat (P = 0.06), and of protein, fat (P = 0.10),
      and ash (P < 0.05) were increased, whereas the relative body composition remained
      unchanged by pST (P > 0.10). On average, muscle protein concentration was
      elevated due to pST (P < 0.01), and, in LW piglets, plasma IGF-I concentration
      was increased (P < 0.10). The results suggest that maternal somatotropin is a
      critical factor in early pregnancy capable of influencing placental nutrient
      transfer and placental growth. It thereby selectively improves the growth
      conditions for the smaller littermates.

PMID- 11465367
TI  - Body composition analysis of the pig by magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) was used to measure, in vivo, the volume of
      several organs and tissues of a total of 111 pigs (males and females) ranging in
      BW from 6.1 to 97.2 kg. In one experiment the in vivo MRI volumes were compared
      to tissue or organ weights obtained by dissection. For internal organs, the
      correlation (R2) between MRI volume and dissected weight ranged from 0.64 (SE of
      estimation = 65 g) for the heart to 0.90 (SE of estimation = 125 g) for the
      liver. The MRI volume of the kidneys was approximately 10% less than the
      dissected weight, whereas the MRI volumes of the heart, liver, and brain exceeded
      the weights of dissected organs by 13, 17, and 26%, respectively. For fat and
      muscle tissues, the correlation between MRI volume and dissected weight ranged
      from 0.82 (psoas muscle) to 0.97 (total right ham muscles). The MRI volume of the
      backfat and shoulder muscles exceeded the dissected weights by approximately 2%,
      whereas the MRI volumes of the ham muscles, jowl fat, longissimus muscle, and
      psoas muscle were 2, 8, 18 and 20% less than their respective weights. In another
      series of experiments, MRI volume measurements of fat and muscle regions (Jowl
      fat, backfat, shoulder muscles, LD muscles, psoas muscles, ham muscles, a 10-cm
      section of the longissimus muscles and overlying fat, and a 15-cm section of the
      ham muscles and overlying fat) were evaluated by stepwise regression for the
      prediction of total body fat, lean, and protein. The best prediction of
      percentage total body fat was obtained using the fat volume from the 10-cm
      section of longissimus muscle and the fat:muscle ratio from the 15-cm section of
      the ham (R2 = 0.9). The best prediction of percentage total body protein was
      obtained using a combination of the volumes (as a percentage of BW) of jowl fat,
      backfat, shoulder muscle, and ham muscle (R2 = 0.62). The combination fat volume
      from the 10-cm section of longissimus muscle, the fat:muscle ratio from the 15-cm
      section of the ham, and the lean volume percentage from the 15-cm section of ham
      provided the best prediction of the percentage of total body lean (R2 = 0.88).

PMID- 11465368
TI  - Effects of three levels of alpha-tocopheryl acetate supplementation to feedlot
      cattle on performance of beef cuts during retail display.
AB  - Retail packages (n = 288; 24 of each product in each treatment group) of inside
      round steaks, T-bone steaks (strip loin and tenderloin), top sirloin steaks, and
      ground beef were used to evaluate effects of dietary supplementation of vitamin E
      to cattle on product performance during retail display. Products from control
      animals and cattle fed 500 IU x animal(-1) x d(-1) or 1,000 IU x animal(-1) x d(
      1) were evaluated. Except for ground beef, dietary supplementation of vitamin E
      increased (P < 0.05) alpha-tocopherol concentrations in beef muscle from cattle
      fed 1,000 IU x animal(-1) x d(-1). Although not all differences were
      statistically significant, retail display-life was greater for all steaks from
      cattle fed 1,000 IU x animal(-1) x d(-1) than for those from control cattle. Ten
      percent of the inside round and tenderloin steaks from cattle fed 1,000 IU x
      animal(-1) x d(-1) had mean overall appearance scores of 3 ("moderately
      undesirable") at 72 to 78 h and 54 to 60 h, respectively, whereas 10% of the
      inside round and tenderloin steaks from control cattle had mean overall
      appearance scores of 3 at 54 to 60 h and 42 to 48 h, respectively. Each of the
      retail cuts in this study (irrespective of the amount of alpha-tocopheryl acetate
      that was fed to the animal that generated it) was categorized as "high,"
      "medium," or "low," based on the alpha-tocopherol concentration in the primal cut
      or ground beef batch from which it originated. Retail cuts in the medium a
      tocopherol concentration category had increased retail display life of 4.0 h for
      ground beef (P < 0.05) over those in the low alpha-tocopherol category. Retail
      cuts in the high alpha-tocopherol concentration category had increased retail
      display life of 10.7 h for inside round steaks and 4.0 h for ground beef (P <
      0.05) over those in the medium concentration category. Vitamin E supplementation
      of cattle at 1,000 IU x animal(-1) x d(-1) for at least 100 d can be used to
      increase retail caselife and to improve the overall color acceptability of steaks
      and ground beef products. Although far from a perfect relationship, these data
      strongly suggest that increasing the alpha-tocopherol concentration in a beef cut
      will increase its retail case life.

PMID- 11465369
TI  - Conjugated linoleic acid changes swine performance and carcass composition.
AB  - Conjugated linoleic acid (CLA) is a collective term for positional and geometric
      isomers of linoleic acid. Dietary CLA has been shown to improve feed efficiency,
      decrease body fat, and increase lean tissue in laboratory animals. We
      hypothesized that CLA would improve performance and carcass composition and would
      be deposited in pork tissues. Diets of 40 crossbred pigs were supplemented with
      CLA to determine its effects on performance and carcass composition. Eight
      replications of five littermate barrows with an initial average weight of 26.3 kg
      were allotted at random to individual pens. Within replication dietary treatments
      containing 0, 0.12, 0.25, 0.5, or 1.0% CLA were assigned at random. Pigs were
      weighed and feed disappearance was determined at 14-d intervals. Average daily
      gain increased linearly as the level of CLA increased in the diet (P < 0.05).
      Average daily feed intake was not affected by the concentration of CLA in the
      diet. Therefore, a linear increase in gain:feed ratio (P < 0.05) was observed.
      Carcasses from animals fed control diets had greater 10th rib backfat than
      carcasses from animals fed CLA (P < 0.05). Ultrasound measurement and carcass
      measurements showed less fat depth over the loin eye at the 10th rib of pigs fed
      doses of CLA (P < 0.05) than that observed for control pigs. Belly hardness
      (firmness) increased linearly as the concentration of CLA in the diet increased
      when bellies were measured for firmness either lean side up (P < 0.001) or lean
      side down (P < 0.05). Loin dissection data demonstrated that CLA produced a
      quadratic treatment effect both for less intermuscular fat (P < 0.001) and less
      subcutaneous fat (P < 0.05) and a linear increase for bone (P < 0.05), although
      finished loin weight only tended to increase (P = 0.08). The CLA concentration
      increased in a linear relationship in both subcutaneous fat (P < 0.001) and lean
      tissue (P < 0.001). Dietary CLA was incorporated into pig tissues and had
      positive effects on performance and body composition.

PMID- 11465370
TI  - Nutritional value of fish meals in the diet for young pigs.
AB  - A series of three experiments was conducted to evaluate the nutritional value of
      fish meals as protein sources in young pigs' diets. Four fish meals (menhaden;
      mackerel, dried at 85 degrees C and 70 degrees C; and herring, dried at 70
      degrees C) were tested. For the first experiment, eight pigs (2 wk old) were
      surgically fitted with ileal cannulas and used to measure apparent digestibility
      of the fish meals over the age period of 3 to 7 wk. Compared with menhaden fish
      meal, mackerel and herring fish meals yielded higher (P < 0.05) ileal
      digestibility values for threonine, serine, alanine, valine, histidine, lysine,
      and arginine and also for the average of all amino acids. Ileal digestibility was
      increased (P < 0.05) as pigs grew. For the second experiment, four different
      diets each containing different fish meals were fed to 120 pigs to evaluate
      growth performance over the age period of 3 to 7 wk. Average daily gain was
      higher (P < 0.07) in pigs fed diets containing either mackerel or herring fish
      meal than in pigs fed menhaden fish meal during 3 to 5 wk of age and was highest
      (P < 0.07) in pigs fed a diet containing mackerel fish meal during 5 to 6 wk of
      age. Gain/feed was higher (P < 0.05) in pigs fed diets containing mackerel and
      herring fish meals than in pigs fed menhaden fish meal. Mackerel dried at 70
      degrees C showed the highest value from the previous two experiments and was
      chosen to measure the relative bioavailability in comparison to spray-dried
      porcine plasma. A classical slope-ratio design was used to measure relative
      bioavailability of mackerel fish meal compared to porcine plasma protein. This
      study showed that mackerel dried at 70 degrees C can replace spray-dried porcine
      plasma with the same bioavailability during d 17 to 29 postpartum with additional
      crystalline lysine and amino acid supplementation to match amino acid profile of
      the spray-dried porcine plasma.

PMID- 11465371
TI  - Performance, digesta characteristics, nutrient flux, plasma composition, and
      organ weight in pigs as affected by dietary cation anion difference and nonstarch
      polysaccharide.
AB  - Two dietary cation anion difference (CAD) levels (-100 and 200 mEq/kg) and two
      dietary nonstarch polysaccharide (NSP) levels (10 and 15%) were used in a 2 x 2
      factorial arrangement in two randomized blocks (trials) to evaluate performance,
      digesta pH and buffer capacity, apparent digestibility, plasma composition, and
      organ weight in pigs. Seven pigs with a mean initial weight of 7.5 kg were used
      in each treatment. Pigs had free access to feed and water during the 3-wk
      experimental period. At the end of the experiment, all pigs were killed
      approximately 2.5 h after addition of fresh feed. Liver, kidneys, and small and
      large intestine were removed and weighed immediately. Gastric and small
      intestinal (divided into two equal parts) digesta were collected. Dry matter, pH,
      buffering capacity, viscosity, acid insoluble ash, mineral content (Na+, K+, and
      Cl-), nitrogen, and gross energy content (only in the second part of the small
      intestine) of the digesta were measured. An interaction (P < 0.05) between
      dietary CAD and dietary NSP was observed for feed intake, growth, apparent
      digestibility of DM and gross energy in the distal small intestine, and chloride
      in the stomach and duodeno-jejunal part of the small intestine. Increasing
      dietary NSP content increased apparent digestibility of DM and chloride in the
      stomach and increased apparent digestibility of DM, chloride, sodium, and
      potassium in the first part of the small intestine. Lowering dietary CAD levels
      significantly increased apparent digestibility of DM in the first part of the
      small intestine and decreased chloride influx in the stomach and the small
      intestine. No significant differences were found for pH, buffering capacity, and
      viscosity of digesta, except the buffering capacity in the second part of the
      small intestine, which was higher (P < 0.05) in the 200 mEq/kg CAD group than in
      the -100 CAD mEq/ kg group. Plasma urea decreased in the low dietary CAD groups
      and plasma ammonia increased in the high NSP groups. Large intestine weight was
      significantly less for the -100 mEq/kg CAD groups than for the 200 mEq/kg CAD
      groups. In conclusion, the effect of CAD on feed intake and growth in pigs
      depends on dietary NSP levels.

PMID- 11465372
TI  - Effect of high temperature and feeding level on energy utilization in piglets.
AB  - The effect of temperature (23 or 33 degrees C) and feeding level on components of
      energy balance was studied in seven groups of individually reared Pietrain x
      (Landrace x Large White) littermate piglets. Within each litter, one pig was
      reared at 23 degrees C and given a predefined feeding level close to ad libitum
      (23AL pigs), one was reared at 33 degrees C and also fed close to ad libitum
      (33AL), and one was reared at 23 degrees C and pair-fed to the 33AL pig (23PF).
      Piglets of one litter were acclimated during 2 to 4 wk to their experimental
      temperature in temperature-controlled rooms before being transferred (one per
      week) to a respiration chamber for measurement of nitrogen and energy balances.
      The average initial BW was 22.4 kg. The data on O2 consumption, CO2 production,
      and physical activity were collected over seven consecutive days and used to
      calculate total heat production (HPtot) and its components: fasting heat
      production (FHP), heat production due to physical activity (HPact), and thermic
      effect of feed (TEF). A preliminary trial was conducted in which heat production
      was measured in three piglets according to a Latin square design at 23, 25, and
      27 degrees C. Total heat production was, but activity-free heat production was
      not, affected by temperature, and no firm conclusions could be drawn as to
      whether 23 degrees C was within the thermoneutral zone of fed piglets. In Trial
      2, the combination of increased temperature and reduced feed intake resulted in a
      20% lesser heat production in 33AL than in 23AL pigs. This was due to a reduction
      in both TEF (-39%) and FHP (0.642 vs 0.808 MJ x d(-1) x kg BW-0.60). Despite the
      shorter duration of standing activity, HPact was slightly higher at 33 degrees C,
      probably due to hyperventilation at this temperature. With similar feeding levels
      (23PF vs 33AL), HPtot and activity-free heat production were less at 33 degrees C
      and energy retention as protein (+6%) and fat (+31%) was increased. Because HPact
      was similar for both treatments, the greater energy retention for 33AL seemed to
      be due to a greater utilization of feed energy or to a reduced maintenance
      requirement (i.e., reduced FHP). However, the type of stress imposed on 23PF and
      33AL pigs was different and may have affected energy metabolism. The results
      suggest that the reduction in heat production of piglets at high ambient
      temperatures is caused by a reduction in voluntary feed intake and differences in
      energetic efficiency. The mechanisms for the lesser efficiency at 23 degrees C
      compared to 33 degrees C (at the same level of feed intake) remain unclear.

PMID- 11465373
TI  - Technical note: using calcium carbonate as an osmolar control treatment for acid
      base studies in horses.
AB  - The efficacy of using calcium carbonate as an osmolar control treatment for acid
      base studies in horses receiving alkalizing compounds was evaluated. Six mares
      were nasogastrically intubated with isomolar quantities of sodium or calcium as
      sodium bicarbonate or calcium carbonate or with water during three treatment
      periods. Doses of the carbonic acid salts were 500 mg/kg sodium bicarbonate mixed
      with 4 L of distilled water (positive control) and 595 mg/kg calcium carbonate
      mixed with 2 L of distilled water to yield isoosmolar treatments. Four liters of
      distilled water served as the negative control. Jugular venous blood samples were
      drawn before intubation and at hourly intervals for 6 h after intubation. The
      serum electrolytes Na+ and K+, blood pH, and HCO3- were determined. The sodium
      bicarbonate treatment increased blood pH and HCO3- (P < 0.01) above both the
      water and CaCO3 treatments. No differences (P > 0.05) were found between the
      water and CaCO3 treatments. These data indicate that calcium carbonate may serve
      as a suitable osmolar control treatment for studying the effects of treatments
      that affect acid-base status of horses.

PMID- 11465374
TI  - The role of altered uterine-embryo synchrony on conceptus growth in the pig.
AB  - This study was conducted to determine whether inducing an embryo-uterine
      asynchrony during the preimplantation period would alter fetal and(or) placental
      size at term. Yorkshire gilts (n = 24) were checked twice daily for estrus and
      bred to a Yorkshire boar 24 h after the first exhibition of estrus. Embryos (1 to
      4 cells) were flushed from the oviducts of each donor gilt on d 2.5 of gestation
      and transferred in equal numbers to the oviducts of a recipient gilt on d 1.5,
      2.5, or 3.5 of the estrous cycle. Gilts were slaughtered on d 112 of gestation
      (calculated on the age of the conceptus) and fetal and placental weight,
      placental surface area, and implantation site lengths were determined. Although
      litter sizes were similar (9.1+/-0.9), conceptuses transferred to d 3.5
      recipients became heavier fetuses (1.44+/-0.05 vs 1.23+/-0.04 kg, P < 0.001),
      with larger placental surface areas (1,793+/-60 vs 1,459+/-43 cm2, P < 0.01), and
      longer implantation sites (32.1+/-1.5 vs 24.9+/-0.6 cm, P < 0.001) than those
      transferred to recipients on d 2.5. These data demonstrate that oviductal
      transfer of embryos into a reproductive tract that is more advanced by as little
      as 24 h can result in alterations in placental growth and function during
      gestation.

PMID- 11465375
TI  - Early postnatal plasma concentrations of testicular steroid hormones, pubertal
      development, and carcass leanness as potential indicators of boar taint in market
      weight intact male pigs.
AB  - Testicular steroid hormone concentrations in plasma of early postnatal male pigs
      were compared with plasma steroid hormone concentrations and androstenone
      concentrations in the fat of pigs at market weight. Positive correlations were
      found between the concentrations of fat androstenone at market weight and the
      concentrations of plasma androstenone (r = 0.46; P < 0.01), estrone sulfate (r =
      0.42; P < 0.01), and testosterone (r = 0.26; P < 0.05) at market weight. These
      correlations were not found in animals that had reached an advanced state of
      pubertal development as judged by high estrone sulfate concentrations in plasma.
      Significant correlations were observed between plasma testosterone concentrations
      at market weight and plasma concentrations of androstenone (r = 0.57; P < 0.05),
      and estrone sulfate (r = 0.49; P < 0.05) in early postnatal animals. However,
      concentrations of androstenone in the fat of market weight animals were not
      correlated with plasma concentrations of estrone sulfate, androstenone, or
      testosterone in early postnatal animals. Plasma concentrations of steroid
      hormones in early postnatal animals cannot, therefore, be used to predict the
      potential for boar taint in the same animals at market weight. In market weight
      animals, there was a negative correlation (r = -0.57; P < 0.01) between backfat
      thickness and concentrations of androstenone in fat. Animals were subsequently
      sorted according to backfat thickness into lean and fat groups of animals. There
      was a strong, negative correlation between back-fat thickness and androstenone
      concentrations in fat (r = -0.80; P < 0.01), as well as a positive correlation
      between plasma androstenone and concentrations of androstenone in fat (r = 0.42;
      P < 0.05) among the lean group of animals. This was not seen in the fat group of
      animals. This suggests that the accumulation of androstenone from plasma into fat
      may be affected by the leanness of the pig.

PMID- 11465376
TI  - Increased plasma follicle-stimulating hormone concentrations in prepubertal gilts
      from lines selected for increased number of corpora lutea.
AB  - Plasma follicle-stimulating hormone (FSH) was evaluated in gilts from two studies
      in which ovulation rate was increased through direct selection for number of
      corpora lutea (CL) to determine whether selection for ovulation rate affected FSH
      secretion during prepubertal development. In the first study, 76 control and 110
      selected gilts of University of Nebraska gene pool lines were bled twice during
      prepubertal development. Plasma FSH concentrations were greater (P < 0.05) at 53
      (13.5%) and 75 (21.3%) d of age in selected than in control gilts. In the second
      study, 254 control gilts, 261 gilts from a line selected for ovulation rate, and
      256 gilts from a line selected for uterine capacity were bled at three
      prepubertal ages. Plasma FSH was greater (P < 0.05), relative to controls, on d
      34 (> 24%), 55 (> 13%), and 85 (> 10%) in White Composite gilts selected for
      either increased ovulation rate or for greater uterine capacity. Unilateral
      ovariectomy and hysterectomy were performed at 160 d of age on random gilts in
      these three lines (n = 377); weights of these organs were evaluated to determine
      whether selection affected their development. Ovarian and uterine weights were
      less (P < 0.01) in the control than in the ovulation rate line. Subsequently,
      ovulation rate was determined during pregnancy (n > or = 130 gilts/line).
      Controls had fewer (P < 0.01) CL (14.6) than gilts of the ovulation rate line
      (17.7) but numbers similar (P > 0.10) to those of gilts of the uterine capacity
      line (14.7). Within each line, plasma FSH only on d 85 correlated positively with
      subsequent ovulation rate (P < 0.03, 0.001, and 0.08; r = 0.17, 0.30, and 0.15
      for control, ovulation rate, and uterine capacity lines, respectively). Ovarian
      weight at 160 d of age also correlated with subsequent ovulation rate (P < 0.03
      and 0.001; r = 0.23 and 0.38) in control and ovulation rate gilts but not in
      uterine capacity gilts (P > 0.10; r = 0.11). Gilts selected for increased number
      of CL, in two independent studies, had greater concentrations of FSH during
      prepubertal development than respective controls. The modest but significant,
      positive association of FSH at 85 d of age with subsequent ovulation rate
      provides additional support for using plasma FSH in prepubertal gilts to
      indirectly select for ovulation rate.

PMID- 11465377
TI  - Relationship between terrain use and performance of beef cows grazing foothill
      rangeland.
AB  - A study was conducted on foothills rangeland to determine whether grazing
      patterns differed among cow breeds and to determine whether there was a
      relationship between individual grazing patterns and performance of beef cows.
      Hereford (HH), Tarentaise (TT), 3/4 Hereford x 1/4 Tarentaise (3H1T), 1/2
      Hereford x 1/2 Tarentaise (HT), and 1/4 Hereford x 3/4 Tarentaise (1H3T) cows
      were observed during the summers of 1997 (n = 183) and 1998 (n = 159). Locations
      of individual cows were recorded two to three times per week during 1.5- to 2.5-h
      periods in the morning by observers on horseback. Statistical models included cow
      breed, age, and nursing status. Data from each year were analyzed separately.
      During 1997 and 1998, nonlactating cows were located at greater (P < 0.05)
      vertical distances from water than lactating cows. In 1998, nonlactating cows
      used steeper (P < 0.05) slopes than lactating cows. However, nonlactating cows
      did not travel as far horizontally from water (P < 0.05) as lactating cows in
      1997. Younger cows (3 yr) traveled further (P < 0.05) from water both vertically
      and horizontally than older cows (5+ yr) in 1997, but not during 1998. Tarentaise
      and 1H3T cows were observed at greater (P < 0.05) vertical distances from water
      than HH cows during both years of the study. During 1998, TT and 1H3T cows used
      steeper (P < 0.05) slopes than HH cows. Using residual correlations, there were
      no consistent relationships between topographic aspects of individual grazing
      locations and cow weight, height, and body condition score. In 1997, cows with
      earlier calving dates and correspondingly heavier calf weaning weights used areas
      that had greater vertical distances to water; however, in 1998 there were no
      relationships (P > 0.05) of calving date and weaning weight with cow location.
      During both years, pregnant and nonpregnant cows used terrain similarly (P >
      0.05), which suggests that cow reproductive performance was not related to
      terrain use. Grazing patterns in foothills rangeland varied among cow breeds.
      Performance of cows that used more rugged topography was similar to cows using
      gentler terrain.

PMID- 11465378
TI  - Effects of tallow on the energy metabolism of wethers fed barley finishing diets.
AB  - A balance trial was conducted to titrate the effects of tallow on the energy
      metabolism of wethers fed barley finishing diets. Six dietary levels of tallow
      (0, 2, 4, 6, 8, or 10%) in a barley finishing diet were fed to six crossbred
      wethers (35+/-1.1 kg) in a randomized complete block design. Diets were 73%
      barley, 10% tallow and(or) bentonite, 10% alfalfa pellets, and 7% supplement.
      There was no effect of tallow level on OM intake (1,103.1+/-51 g/d), OM
      digestibility (84+/-0.9%), GE digestibility (83+/-1.1%), or cell solubles
      digestibility (84.2+/-1.2%). The level of tallow quadratically decreased ADF
      digestibility (P < 0.05), methane emissions, and methane energy as a percentage
      of GE P < 0.01). There were linear increases in dietary GE (megacalories per
      kilogram of OM [P < 0.01]), dietary DE (megacalories per kilogram of OM [P <
      0.05]), and dietary ME (megacalories per kilogram of OM [P < 0.01]), as dietary
      tallow increased. Numbers of ruminal protozoa (Entodinium spp. and Polyplastron
      sp.) decreased linearly (P < 0.05) with increased level of tallow. The energy
      value of tallow (calculated by difference) was low. The total-tract fatty acid
      digestibility of tallow was calculated by linear regression, without intercept,
      after accounting for the fatty acids digested from the base diet (0% tallow fed
      to a wether in a period). Fatty acids of the same carbon length were pooled for
      the regression analysis. All linear regressions were significant (P < 0.10)
      indicating no effect of tallow level on fatty acid digestibility. Lauric acid had
      low digestibility. The high digestibility of all C16 (89%) and C18 (104%) fatty
      acids suggests an effect of tallow on endogenous and microbial fatty acid
      excretion. Fatty acid digestibility was probably a minor contributor to the low
      energy content of tallow, calculated by difference, in these diets.

PMID- 11465379
TI  - Influence of supplementary fibrolytic enzymes on the fermentation of corn and
      grass silages by mixed ruminal microorganisms in vitro.
AB  - This study was done to determine the effectiveness of supplementary enzymes at
      increasing the fiber digestion by ruminal microorganisms and to assess whether
      enzyme activity limits the rate of fiber digestion in ruminal digesta. In vitro
      comparisons of enzyme activities in two feed enzyme preparations (A and B) with
      enzyme activities extracted from ruminal fluid indicated that the addition of
      fibrolytic enzymes at the application rates recommended by the manufacturers
      would not be expected to increase significantly glycanase and polysaccharidase
      activities in ruminal fluid. Preparations A and B both increased (P < 0.001) the
      rate of gas production from freeze-dried corn and grass silages in in vitro
      incubations with ruminal fluid, but only at concentrations much higher than
      recommended application rates. Autoclaved controls had little or no effect.
      Ultrafiltration of enzyme B indicated that most stimulation was due to components
      >100 kDa, which is consistent with the cause of the stimulation being enzyme
      activity. Fibrolytic enzymes from other sources were also able to stimulate gas
      production: increased rates of gas production were observed in seven out of eight
      combinations of "cellulase" and corn or grass silage (P < 0.05). The comparison
      of glycanase and polysaccharidase activities with gas-stimulatory activity in the
      different enzyme preparations indicated that the highest correlation was between
      increased gas production and enzyme activity against microgranular cellulose (P <
      0.05). In a wider range of fibrolytic enzyme preparations, those with endo-(beta
      1,4)- or exo-(beta-1,4)-xylanase activity equal to that of preparation A did not
      produce similar increased rates of fermentation of corn silage when glucanase
      activity was low (P > 0.05). In contrast, preparations with glucanase activity
      similar to enzyme A gave at least as great (P < 0.05) an improvement in gas
      production than enzyme A, irrespective of xylanase activity. It was concluded
      that enzyme activity, probably a type of endo-(beta-1,4)-glucanase activity,
      limits the rate of fermentation of corn and grass silage in the rumen. Enzyme
      supplements of the type used in these experiments are unlikely to possess
      sufficient activity to overcome this limitation by direct application to ruminal
      digesta, implying that treatment of the ration prefeeding will be key to
      harnessing the potential of exogenous fibrolytic enzymes in ruminant nutrition.

PMID- 11465380
TI  - Influence of alpha-linked glucose on sodium-glucose cotransport activity along
      the small intestine in cattle.
AB  - Thirteen steers (378+/-23 kg) were used in a split-plot experimental design to
      evaluate the effect of small intestinal carbohydrate on sodium-glucose
      cotransport in brush border membrane vesicles prepared from five equidistant
      sites along the small intestine. The steers consumed 7.2+/-0.4 kg/d ground fescue
      hay and soybean meal-based supplement and were infused ruminally or postruminally
      with a partial alpha-amylase starch hydrolysate (914.5+/-8.3 g/d) for 7 d. On d
      7, five equidistant 1-m small intestinal sections were harvested and frozen in
      liquid N for later preparation of brush-border membrane vesicles. Maltase
      activity of the homogenate and vesicle preparations changed (P < 0.001; lowest in
      the duodenum, highest in the jejunum) and alkaline phosphatase decreased (P <
      0.001) along the small intestine. With respect to the original homogenates, the
      vesicle preparations were enriched 9.80+/-0.83- and 7.64+/-0.67-fold for alkaline
      phosphatase and maltase, respectively; enrichments were not different between
      treatments (P = 0.76 and 0.39, respectively). However, alkaline phosphatase and
      maltase enrichment changed (P < 0.001) along the small intestine. Recoveries of
      alkaline phosphatase and maltase activities (25.0+/-0.2% and 19.5+/-0.2%,
      respectively) in the vesicle preparation were not affected (P = 0.29 and 0.21,
      respectively) by treatment but changed (P < 0.001) along the intestine. Recovery
      of protein in the vesicle preparation was 2.60+/-0.01% and was not affected by
      treatment or intestinal site. Sodium-glucose cotransport activity (220+/-44 pmol
      x mg(-1) x s(-1)) was not affected (P = 0.34) by treatment but did change (P <
      0.001; lowest in the ileum, highest in the proximal and mid-jejunum) along the
      small intestine. Apparent Km of the sodium-glucose cotransporter for glucose was
      62.8+/-5.8 microM. The specific activity of maltase was highest in the jejunum,
      and sodium-glucose cotransport was highest in the first two jejunal sites.
      However, duodenal maltase activity was lowest and ileal sodium-glucose
      cotransport activity was lowest. Sodium-glucose cotransport activity may limit
      small intestinal starch assimilation in the distal small intestine. It does not
      seem that glucose arising from carbohydrate hydrolysis regulates activity of
      sodium-dependent glucose transport in cattle.

PMID- 11465381
TI  - Effects of barley grain processing on the site and extent of digestion of beef
      feedlot finishing diets.
AB  - Effects of extent of barley rolling on chewing activities, ruminal fermentation,
      and site and extent of digestion were evaluated for feedlot finishing cattle
      diets in a 4 x 4 Latin square design. Four Jersey steers (452 kg), cannulated in
      the rumen and duodenum, were used. Barley grain was temper-rolled to four
      extents: coarse, medium, medium-flat, and flat, which were expressed as
      processing index (PI, volume weight of barley after processing expressed as a
      percentage of its volume weight before processing, DM basis) and equivalent to
      82, 75, 70, and 65%, respectively. Diets consisted of 9.7% barley silage, 86%
      temper-rolled barley, and 4.3% other ingredients (DM basis). Steers were offered
      ad libitum access to a total mixed ration once daily. Dry matter intake was not
      affected (P > 0.15) by PI of barley. Digestibility of OM in the rumen and in the
      total tract were numerically lower (P = 0.13) for steers fed coarsely rolled
      barley than for steers fed more extensively processed barley. Digestibility of
      starch in the total tract was linearly increased (P = 0.02) with grain
      processing, but NDF digestion was not affected by processing (P > 0.15).
      Digestibility of CP did not differ in the rumen but tended (P = 0.08) to increase
      in the total tract with increased processing of barley. Flow of microbial
      nitrogen to the duodenum was approximately one-third lower (linear effect, P =
      0.06) for steers fed coarsely rolled barley than for steers fed further rolled
      barley. Increased grain processing tended to decrease (linear effect, P = 0.08)
      rumination time without affecting eating time. These results indicate that
      optimal degree of rolling for barley fed to feedlot cattle corresponded to a PI
      of 75% or lower. Coarsely rolled barley is not recommended because it resulted in
      the lowest digestibility and lowest microbial protein synthesis. Processing
      barley to attain a PI less than 75% resulted in marginal improvements in feed
      digestion, but rumination time decreased, which could lead to problems associated
      with acidosis if lower-fiber diets are used.

PMID- 11465382
TI  - Urea flux in beef steers: effects of forage species and nitrogen fertilization.
AB  - The effects of two forage species and N levels on urea kinetics and whole-body N
      metabolism were evaluated in eight Angus steers (initial BW 217+/-15 kg). In a
      replicated, 4 x 4 Latin square design, steers were fed gamagrass (Tripsacum
      dactyloides L.) or switchgrass (Panicum virgatum L.), each of which had 56.2 (LO)
      or 168.5 (HI) kg of N fertilization per hectare. Diets provided adequate energy
      for 0.5 kg ADG. Nitrogen balance and urea kinetics were measured from d 22 to 27
      of each period. Urine samples collected during intravenous infusion of bis 15N
      urea were used to calculate production and recycling of urea N from relative
      abundance of urea isotopomers. Jugular blood serum was analyzed for serum urea N
      (SUN). Gamagrass differed from switchgrass (P < 0.05) in daily DMI (4,273 vs
      4,185 g), N intake (72 vs 67 g), DM digestibility (61.0 vs 63.6%), fecal N (30.6
      vs 28.3 g/d), urine urea N (10.5 vs 8.0 g/d), and percentage of urinary N present
      as urea N (53.5 vs 40.0%). After adjustment for differences in N intake, fecal N
      still tended to be greater (P < 0.09) for gamagrass than for switchgrass. The LO
      differed from the HI (P < 0.01) in daily N intake (63 vs 76 g), DM digestibility
      (61.3 vs 63.3%), urine N (13.6 vs 25.9 g/d), and N retained as a percentage of N
      digested (57.3 vs 43.5%). Compared to switchgrass, gamagrass had greater SUN, N
      digestibility, and N digested as N level increased (forage x N level
      interactions, P < 0.05). As N level increased, N retention increased from 19.5 to
      23.5 g/d in gamagrass and decreased from 20.5 to 18.1 g/d in switchgrass
      (interaction, P < 0.07). The HI group was greater than the LO intake group (P <
      0.03) in endogenous production of urea N (44.4 vs 34.0 g/d), gut entry rate of
      urea N (31.6 vs 28.2 g/d), and the amount of urea N that re-entered the ornithine
      cycle (9.4 vs 7.9 g/d). However, the percentage of urea N entering the
      gastrointestinal tract that was recycled was constant among treatments (29.1%),
      indicating that almost 70% of the urea N that entered the gastrointestinal tract
      was potentially available for anabolic purposes of the steers as a component of
      microbial products that were absorbed or excreted in the feces. In summary, N
      levels affected N metabolism of steers more when they were fed gamagrass than
      when they were fed switchgrass. Although the absolute amounts of N moving through
      the system changed with variations in intake, the proportions remained similar,
      with a greater efficiency of N use at low N intakes.

PMID- 11465383
TI  - Effect of nitrogen source in high-concentrate, low-protein beef cattle diets on
      microbial fermentation studied in vivo and in vitro.
AB  - In Exp. 1, four Holstein heifers (112+/-5.5 kg BW) fitted with ruminal cannulas
      were used in a 4 x 4 Latin square to evaluate the effects of N source on ruminal
      fermentation and urinary excretion of purine derivatives. A 2 x 2 factorial
      arrangement of treatments was used; the factors were the type of protein source
      (soybean meal, SBM, vs a 50:50 mixture of fish meal and corn gluten meal, FMCGM)
      and the partial substitution of protein source by urea (with vs without). Heifers
      were allowed to consume concentrate and barley straw on an ad libitum basis.
      Barley straw:concentrate ratio (12:88) and average ruminal pH (6.25) were not
      affected (P > 0.05) by treatment. Ruminal NH3 N concentration and urinary
      excretion of purine derivatives were not affected (P > 0.05) by supplemental N
      source. In situ CP degradability of supplemented SBM was very low (50%). In Exp.
      2, eight dual-flow continuous-culture fermenters were used to study diet effects
      on microbial fermentation and nutrient flow, using forage:concentrate ratio,
      solid and liquid passage rates, and pH fluctuation to simulate in vivo
      conditions. The treatment containing SBM without urea reached the greatest total
      VFA concentration (P < 0.01), molar percentage of acetate (P < 0.05), and NH3 N
      concentration (P < 0.05), followed by treatments with partial substitution of
      protein source by urea, and finally by the treatment containing FMCGM. True OM
      digestion tended to increase (P = 0.13) in treatments containing SBM. These
      results suggest that amino N from SBM and NH3 N concentration stimulated nutrient
      digestion. Microbial protein synthesis was lowest in treatments with FMCGM and
      without urea, indicating that rapidly available N limited microbial growth. The
      low CP degradability of SBM observed may have contributed to the limitation in N
      supply for microbial growth. Efficiency of microbial protein synthesis increased
      in treatments containing urea (P < 0.05). Protein source affected total (P <
      0.05) and essential AA (P < 0.10) flows, which were greater in treatments
      containing FMCGM. Partial replacement of protein supplements by urea did not
      affect total and essential AA flows. Because mean dietary protein contribution to
      total N effluent was 46%, the AA profile of supplemental protein sources had a
      great impact on total AA flow and its profile.

PMID- 11465384
TI  - Rapid communication: mapping of the bovine stearoyl-coenzyme A desaturase (SCD)
      gene to BTA261.

PMID- 11465385
TI  - Fatal on-farm injuries among youth 16 to 19 years of age: 1982-1994.
AB  - Data from the Vital Statistics Mortality (VSM) public use file and the National
      Traumatic Occupational Fatalities (NTOF) surveillance systems were used to
      describe fatal injuries among youth 16-19 years of age in the United States that
      occurred on farms for the years 1982 through 1994. The VSM captures all deaths in
      the United States, while the NTOF only captures occupational injury deaths. There
      were 550 total on-farm fatalities to youth 16-19 years of age in the VSM, and 221
      occupational on-farm deaths from the NTOF for the same age group. These numbers
      suggest that 40% of the on-farm deaths were occupational. It was found that the
      proportions of deaths attributable to work increased with age. Fatality rates for
      on-farm nonoccupational deaths decreased slightly during the time period (from
      8.4 deaths/100,000 for 1982-1985 to 6.8 deaths/100,000 for 1991-1994), while on
      farm occupational fatality rates dropped dramatically (12.0 deaths/100,000 for
      1982-1985 down to 4.9 deaths/100,000 for 1991-1994). The leading causes of death
      for on-farm occupational fatalities were machinery (54%) and electrical current
      (20%). The most common causes of on-farm fatalities that were nonoccupational
      were drowning (38.9%) and firearms (28.6%). For the years 1991 through 1994,
      drowning and firearms accounted for approximately the same number of on-farm
      deaths as machinery. Nonoccupational risks are a concern for youth 16-19 years of
      age on the farm.

PMID- 11465386
TI  - Documentation of hazards and safety perceptions for mechanized logging operations
      in East Central Alabama.
AB  - The logging industry remains one of the most hazardous in the nation. Despite
      more stringent safety regulations and improvements in equipment safety features,
      the rate of logging fatalities has decreased at a much lower rate than the
      decrease in the rate of illnesses and injuries in the same occupation. The
      objective of this research was to identify and assess the hazards associated with
      logging operations in the Southeast region of the U.S. and propose interventions,
      taking into consideration the fact that, currently, most operations in the region
      are fully mechanized. Five logging crews in East Central Alabama participated in
      the study and were observed repeatedly during their normal operations.
      Researchers observed loggers engaging in multiple unsafe behaviors, but none of
      those led to an injury. The incidence of unsafe behaviors may be due in part to a
      lack of awareness of the hazards. Results indicate that Occupational Safety and
      Health Administration (OSHA) regulations appear to have little influence on
      logging safety. Loggers believe that most safety training recommendations are
      difficult to implement and negatively impact productivity. Thus, there seem to be
      fundamental drawbacks in the logging industry regarding effective delivery of
      safety training to loggers. The present study was a joint venture by the
      Industrial and Systems Engineering and Psychology departments of Auburn
      University, with support from the United States Forest Service (USFS).

PMID- 11465387
TI  - Interviews with widows following fatal farming incidents.
AB  - Farm families have been identified traditionally with a strong family bond
      resulting from both living and working together. When a farming fatality occurs,
      surviving family members are left to deal with not only the tragedy of losing a
      loved one, but also the loss of a coworker. Although every family experiencing a
      loss will deal with bereavement issues, farm families are faced with additional
      challenges that differentiate them from other family situations. A qualitative
      research methodology was employed to understand the complex mix of challenges
      facing farm families after the death of a family member. Semi-structured
      interviews were conducted with farming widows in Kentucky to explore the stresses
      and challenges related to the farm business, family relationships, and the mental
      health of the individual members. Becoming the primary decision maker for the
      farm and household was a difficult role for the widows. Economic issues were an
      underlying consideration in many aspects of the experiences and changes they
      encountered. The need to make economic decisions almost immediately while
      continuing the necessary chores to maintain crops and livestock was very
      stressful and left little time for bereavement. Often the support from family,
      friends, and neighbors went beyond emotional comforting to providing help with
      farm chores and guidance on financial decisions. In developing resources for farm
      families in similar circumstances, it is important to understand how intertwined
      their lives are with their environment and the economics of the business.

PMID- 11465388
TI  - A qualitative assessment of children's farm safety day camp programs.
AB  - In order to increase farm safety awareness and teach children good safety habits,
      farm safety day camp programs have been initiated in many communities. For the
      most part, the effectiveness of the programs is unknown because few evaluations
      have been performed. The purpose of this project was to qualitatively assess the
      overall strengths and weaknesses of farm safety day camp programs and to generate
      recommendations for future programs. Interviews, a literature search, and
      observations were used to identify strengths and weaknesses of the farm safety
      day camp programs. Major strengths of the programs are that: 1) positive
      attention is given to agriculture and agricultural safety; 2) programs are hands
      on, interactive, and fun; 3) children gain knowledge about farm safety; 4)
      programs bring a community together to work toward a common goal; and 5) children
      talk to parents about safety. Key weaknesses of farm safety day camp programs are
      that: 1) there is a lack of parental involvement in many of the programs; 2) it
      is hard to change patterns of behavior in one day; 3) programs are expensive and
      time consuming; 4) curricula may include content that is inaccurate or
      inappropriate for the age of participants; and 5) evaluation is difficult. When
      done well, farm safety day camp programs can teach children about safety and
      influence safety practices affecting children on the farm. Recommendations for
      future farm safety day camp programs are: 1) ensure that child-development
      principles are applied to all aspects of program activities and curricula; 2)
      provide session leaders with accurate and relevant content; 3) increase parental
      involvement; and 4) address safety issues throughout the year.

PMID- 11465389
TI  - Metabolism of bisphenol A in isolated rat hepatocytes and oestrogenic activity of
      a hydroxylated metabolite in MCF-7 human breast cancer cells.
AB  - 1. The metabolites of bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane) in
      freshly isolated rat hepatocytes and the oestrogenic activities of BPA and its
      metabolites, particularly 3-hydroxybisphenol A (3-OH-BPA), in MCF-7 cells and
      competitive binding assays have been studied, respectively. 2. During a 2-h
      incubation, almost all of the BPA (0.25 mM) added to the hepatocyte suspensions
      was rapidly converted to a major conjugate, monoglucuronide (approximately 75% of
      total metabolites), and two minor conjugates, which were tentatively identified
      as monosulphates of BPA and a hydroxylated intermediate, 3-OH-BPA, as determined
      by mass spectroscopy coupled with HPLC or GC/MS. On the other hand, free 3-OH-BPA
      was identified as a trace metabolite, whose level was approximately 1 or 2 microM
      at 1 h in hepatocyte suspensions treated with 0.25 or 0.5 mM BPA, respectively.
      3. In another experiment, 3-OH-BPA as well as BPA displaced competitively 17beta
      oestradiol bound to the recombinant human oestrogen receptor alpha in a
      concentration dependent-manner: IC50 of diethylstilbestrol, BPA and 3-OH-BPA were
      approximately 2.5 x 10(-8), 10(-5) and 5 x 10(-5) M, respectively. Further, BPA
      and 3-OH-BPA at intermediate concentrations (10(-7) - 10(-6) M) caused
      proliferation of MCF-7 human breast cancer cells, whereas the effect of BPA was
      more potent than that of 3-OH-BPA. At higher concentrations, both BPA (> 10(-4))
      and 3-OH-BPA (> 10(-5) M) were cytotoxic. 4. Based on the proliferative potency
      in MCF-7 cells and the IC50 for the competitive binding, the oestrogenic activity
      of 3-OH-BPA was less than that of BPA. These results indicate that BPA itself
      rather than its metabolite acts as a xeno-oestrogen and that 3-OH-BPA is
      cytotoxic, possibly acting via reactive semiquinone and/or quinone metabolites,
      rather than a xeno-oestrogenic mechanism, in MCF-7 cells.

PMID- 11465390
TI  - Species differences in beta-oxidative metabolism of a thromboxane A2-receptor
      antagonist [(+)-S-145] in rat, dog and monkey.
AB  - 1. The formation of beta-oxidized metabolites from (+)-S-145 [(+)-(Z)-7-[(1R, 2S,
      3S, 4S)-3-(benzenesulphonamide)bicyclo-[2.2.]-hept-2-yl]-5-heptenoic acid] by
      liver homogenates were compared between rat, dog and monkey. Species differences
      were found in hepatic beta-oxidation capacities. The results agree with the
      qualitative and quantitative differences in beta-oxidized metabolite proportions
      among these species observed in vivo. 2. The activities of microsomal (+)-S-145
      CoA synthesis, the initial step of the beta-oxidation, were determined. Species
      differences in their intrinsic clearances primarily agreed with those of the beta
      oxidized metabolite formation. 3. (+)-S-145-CoA oxidation activities towards (+)
      S-145-CoA by liver homogenates were much higher than the beta-oxidized metabolite
      formation in all species, indicating that formed (+)-S-145-CoA was immediately
      beta-oxidized in peroxisomes. The species differences were inconsistent with
      those of beta-oxidized metabolite formation in vitro. 4. Therefore, quantitative
      differences of hepatic (+)-S-145 beta-oxidation capacity in rat, dog and monkey
      were considered to be mainly due to the species difference in (+)-S-145-CoA
      formation.

PMID- 11465391
TI  - Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent
      competitive inhibition by 8-phenyltheophylline.
AB  - 1. Humans are exposed in vivo to methylxanthines by dietary ingestion, as well as
      from their use as therapeutic agents. The inhibitory effect of a series of these
      compounds on high-affinity phenacetin O-deethylase activity in the human liver
      microsomal fraction, a measure of CYP1A2 activity, has been evaluated. 2.
      Paracetamol, the product of phenacetin O-deethylase activity, was analysed by gas
      chromatography/negative-ion mass spectrometry using a novel
      bistrifluoromethylbenzoyl/ trimethylsilyl derivative, and incubation conditions
      for assessing high-affinity phenacetin O-deethylase activity were examined and
      optimized. 3. 1-Methylxanthine, caffeine, theophylline, 8-methylxanthine,
      pentoxyfylline and 3isobutyl-1-methylxanthine caused moderate inhibition with
      IC50 = 260, 140, 120, 100, 62 and 36 microM respectively. 4. 8-Phenyltheophylline
      was a potent competitive inhibitor of high-affinity phenacetin O-deethylase
      activity with an IC50 = 0.7 microM and Ki = 0.11 microM. 5. The specificity of
      inhibition by 8-phenyltheophylline was assessed by measuring its effect on
      debrisoquine 4-hydroxylase (CYP2D6), terfenadine hydroxylase (CYP3A4),
      chlorzoxazone 6-hydroxylase (CYP2E1) and tolbutamide 4-hydroxylase (CYP2C9)
      activities in human liver microsomal fraction. No inhibition of any of these
      activities was observed. 6. The potency and specificity of 8-phenyltheophylline
      as an inhibitor of human hepatic CYP1A2 indicate that the compound may be useful
      as a chemical inhibitor of this enzyme for further in vitro studies.

PMID- 11465392
TI  - Human adult and foetal liver sulphotransferases: inhibition by mefenamic acid and
      salicylic acid.
AB  - 1. The aim was to see whether mefenamic acid and salicylic acid had different
      inhibition profiles for SULT1A1 (substrate: 4-nitrophenol) and SULT1A3 (dopamine)
      activities and on (-)-salbutamol and minoxidil sulphation rates in the human
      adult and mid-gestational foetal livers. 2. The activity (pmolmin(-1) mg(-1) of
      SULT1A1 was 662 +/- 78 (adult) and 246 +/- 159 (foetus; p = 0.003) and that of
      SULT1A3 was 24 +/- 4 (adult) and 121 +/- 90 (foetus; p = 0.030). The rate (pmol
      min(-1) mg(-1)) of (-)-salbutamol sulphation was 109 +/- 27 (adult) and 117 +/-
      34 (foetus; p = (0.144) and that of minoxidil sulphation was 202 +/- 38 (adult)
      and 108 +/- 44 (foetus; p = 0.001). 3. With mefenamic acid as an inhibitor, the
      IC50 (microM) for SULT1A1 was 0.2 +/- 0.004 (adult) and 0.01 +/- 0.002 (foetus; p
      = 0.001); for SULT1A3 it was 76 +/- 6 (adult) and 77 +/- 13 (foetus; p = 0.889);
      for the rate of ( )-salbutamol sulphation it was 0.07 +/- 0.005 (adult) and not
      determinable (foetus) and for minoxidil sulphation it was 1.6 +/- 0.7 (adult) and
      0.15 +/- 0.04 (foetus; p = 0.076). 4. With salicylic acid as an inhibitor, the
      IC50 (microM) for SULT1A1 was 30 +/- 2 (adult) and 25 +/- 1 (foetus; p = 0.011);
      for SULT1A3 it was 690 +/- 36 (adult) and 570 +/- 16 (foetus; p = 0.229); for the
      rate of ( )-salbutamol sulphation it was 93 +/- 11 (adult) and 344 +/- 42
      (foetus; p = 0.010); with minoxidil as substrate, the IC50 was not determinable.
      5. In summary, SULT1A1, SULT1A3 and the sulphotransferases towards (-)-salbutamol
      and minoxidil had measurable activities in the mid-gestational human foetal
      liver. Mefenamic acid was a more potent inhibitor than salicylic acid of both
      human adult and foetal liver SULT1A1 and SULT1A3 activities. Foetal liver SULT1A1
      was more susceptible than adult liver SULT1A1 to inhibition by mefenamic acid and
      salicylic acid. These results are consistent with the view that
      sulphotransferases develop early in the human foetal liver and drugs may inhibit
      their activities.

PMID- 11465393
TI  - Specificity of 17beta-oestradiol and benzo[a]pyrene oxidation by polymorphic
      human cytochrome P4501B1 variants substituted at residues 48, 119 and 432.
AB  - 1. Eight human cytochrome P4501B1 (CYP1B1) allelic variants, namely Arg48 Ala119
      Leu432, Arg48 Ala119 Val432 Gly48 Ala119 Leu432, Gly48 Ala119 Val432, Arg48
      Ser119 Leu432, Arg48 Ser119 Val432, Gly48 Ser119 Leu432 and Gly48 Ser119 Va1432
      (all with Asn453), were expressed in Escherichia coli together with human NADPH
      P450 reductase and their catalytic specificities towards oxidation of 17beta
      oestradiol and benzo[a]pyrene were determined. 2. All of the CYP1B1 variants
      expressed in bacterial membranes showed Fe2+.CO versus Fe2+ difference spectra
      with wavelength maxima at 446 nm and they reacted with antibodies raised against
      recombinant human CYP1B1 in immunoblots. The ratio of expression of the reductase
      to CYP1B1 in these eight preparations ranged from 0.2 to 0.5. 3. CYP1B1 Arg48
      variants tended to have higher activities for 17beta-oestradiol 4-hydroxylation
      than Gly48 variants, although there were no significant variations in 17beta
      oestradiol 2-hydroxylation activity in these eight CYP1B1 variants.
      Interestingly, ratios of formation of 17beta-oestradiol 4-hydroxylation to 2
      hydroxylation by these CYP1B1 variants were higher in all of the Val432 forms
      than the corresponding Leu432 forms. 4. In contrast, Leu432 forms of CYP1B1
      showed higher rates of oxidation of benzo[a]pyrene (to the 7,8-dihydoxy-7,8
      dihydrodiol in the presence of epoxide hydrolase) than did the Val432 forms. 5.
      These results suggest that polymorphic human CYP1B1 variants may cause some
      altered catalytic specificity with 17beta-oestradiol and benzo[a]pyrene and may
      influence susceptibilities of individuals towards endogenous and exogenous
      carcinogens.

PMID- 11465394
TI  - Trends in incidence of primary brain tumors in the United States, 1985-1994.
AB  - Brain tumor incidence has increased over the last 20 years in all age groups,
      both overall and for specific histologies. Reasons attributed to these increases
      include increase in lymphoma due to HIV/AIDS, introduction of computed
      tomography/magnetic resonance imaging, and changes in coding/classification. The
      purpose of this study was to describe overall and histologic-specific incidence
      trends in a population-based series of primary benign and malignant brain tumors.
      Data from the Central Brain Tumor Registry of the United States from 1985 through
      1994 were used to determine incidence trends in the broad age groups 0-19, 20-64,
      and > or = 65 years, both overall and for selected histologies. Poisson
      regression was used to express trends as average annual percentage change.
      Overall, incidence increased modestly (annual percentage change 0.9%, 95%
      confidence interval, 0.4, 1.4). When lymphomas were excluded, this result was not
      statistically significant (annual percentage change 0.5%, 95% confidence
      interval, -0.1, 1.1). Specific histologies that were increasing were lymphomas in
      individuals aged 20 to 64 years and in males aged 65 years or older, ependymomas
      in the population aged 20 to 64 years, nerve sheath tumors in males, and
      pituitary tumors in females. Increases that were not specific to any population
      subgroup were seen for glioblastoma, oligodendrogliomas, and astrocytomas,
      excluding not otherwise specified (NOS) tumors. Corresponding decreases were
      noted for NOS, astrocytoma NOS, and glioma NOS. Increasing incidence trends for
      lymphomas were consistent with previous literature. Improvements in diagnostic
      technology in addition to changes in classification and coding were likely to be
      responsible for decreases seen in incidence of NOS subgroups and corresponding
      increases in glioma subgroups. In contrast, the increases identified for
      ependymomas, nerve sheath tumors, and pituitary tumors were less likely to be
      artifacts of improvements in diagnosis, and they warrant further study.

PMID- 11465395
TI  - Prevalence estimates for primary brain tumors in the United States by behavior
      and major histology groups.
AB  - Prevalence rates are used to supplement descriptions of disease and are
      unavailable for all primary brain tumors in the United States. Data from two
      population-based tumor registries were obtained from the Central Brain Tumor
      Registry of the United States and used to compute age-specific incidence rates
      (1985-1994) and survival curves for further use in a statistical model to
      estimate prevalence rates. Prevalence rates were then used to estimate the number
      of individuals living with a brain tumor diagnosis in the U.S. population for the
      year 2000. The overall incidence rate in these regions is 13.8 per 100,000 with 2
      , 5-, and 10-year survival rates of 58%, 49%, and 38%, respectively. The
      prevalence rate for all primary brain tumors is 130.8 per 100,000 with
      approximately 350,000 individuals estimated to be living with this diagnosis in
      the United States in 2000. The prevalence rate for malignant tumors, 29.5 per
      100,000, is similar to previous reports. The prevalence rate for benign tumors,
      97.5 per 100,000, is new. Unlike incidence data, the proportion (and expected
      number) of existing benign tumors (75%, 267,000) is considerably greater than
      that for malignant tumors (23%, 81,000), reflecting the better prognosis of
      benign tumors diagnosed in individuals younger than 60 years old. These data
      underscore the impact of primary brain tumors in the U.S. health care system and
      emphasize the need for quality-of-life considerations, particularly for those
      long-term survivors of benign tumors.

PMID- 11465396
TI  - Stereotactic radiosurgery of residual or recurrent craniopharyngioma, after
      surgery, with or without radiation therapy.
AB  - This study evaluated the role of stereotactic radiosurgery in the multimodality
      management of craniopharyngioma patients whose prior therapies failed. Ten
      consecutive patients (3 males and 7 females) had radiosurgery for
      craniopharyngioma during a 10-year interval. Their ages ranged from 9 to 64 years
      (median, 14.5 years). The median interval between diagnosis and radiosurgery was
      46.5 months. In total, 12 stereotactic radiosurgical procedures were performed to
      control the solid component of the tumor (2 intrasellar and 10 suprasellar
      tumors). The median tumor volume was 1.35 cm3. One to 9 isocenters with different
      beam diameters were used; the median marginal dose was 16.4 Gy; and the dose to
      the optic apparatus was limited to less than 8 Gy. Clinical and imaging follow-up
      data were obtained at a median of 63 months (range, 13-150 months) from
      radiosurgery. Overall, 7 of 12 tumors became smaller or vanished within a median
      of 8.5 months. Prior visual defects objectively improved in 6 patients. One
      patient with prior visual defect deteriorated further and lost vision 9 months
      after radiosurgery. Multimodality therapy is often necessary for patients with
      refractory solid and cystic craniopharyngiomas. Stereotactic radiosurgery is a
      reasonable option in select patients with small recurrent or residual
      craniopharyngioma.

PMID- 11465397
TI  - Survival and recurrence factors in adult medulloblastoma: the M.D. Anderson
      Cancer Center experience from 1978 to 1998.
AB  - Medulloblastoma is a rare adult primary brain tumor for which limited
      retrospective studies are available to elucidate natural history or to guide
      therapy. A retrospective chart and imaging review of adult patients (aged >18
      years) with medulloblastoma was performed to identify survival and prognostic
      factors. Fifty-seven patients were evaluated at the University of Texas M.D.
      Anderson Cancer Center from 1978-1998. Statistical analysis of prognostic factors
      and overall survival was performed for a subgroup of 28 patients who were
      followed exclusively at our institution from the time of diagnosis until death or
      last follow-up. These 28 patients had an overall survival of 91% at 3 years and
      84% at 5 years, whereas median survival was not reached after a median follow-up
      of 168 weeks (range, 9-602 weeks). Progression-free survival for all patients was
      68% at 3 years and 62% at 5 years, and was not statistically different between
      poor- and standard-risk patients. Univariate analysis of clinical features, such
      as age, sex, extent of local disease, extent of resection, and use of adjuvant
      chemotherapy, did not identify any prognostic variables for survival among the 28
      patients. Patterns of recurrence revealed that the posterior fossa was the most
      common site (56%), followed by bone marrow (25%). Adult medulloblastoma appears
      to have a favorable prognosis after treatment with maximally surgically feasible
      resection followed by craniospinal irradiation. Optimal treatment remains to be
      clarified, as both standard-risk and poor-risk patients have prolonged disease
      free survival. The marked difference between survival and progression-free
      survival suggests that salvage therapy, usually with combination chemotherapy in
      this cohort of patients, is of benefit. More formal analysis of the survival
      benefit was not possible, however, because of the small number of patients
      treated at recurrence with any one therapeutic regimen.

PMID- 11465398
TI  - Long-term quality of life and neuropsychologic functioning for patients with CNS
      germ-cell tumors: from the First International CNS Germ-Cell Tumor Study.
AB  - This study evaluated the quality of life and neuropsychologic functioning among
      patients enrolled between 1989 and 1993 in the First International CNS Germ-Cell
      Tumor Study. Quality-of-life questionnaires (Short Form-36 or Child Health
      Questionnaire) were completed on 43 patients at median follow-up of 6.1 years
      after diagnosis (range, 4.5-8.8 years), and intellectual and academic testing was
      performed on 22 patients. Psychosocial and physical functioning of patients aged
      19 years and older at follow-up was within the average range, whereas the same
      functioning for patients aged 18 years and younger, as reported by their parents
      at follow-up, was low average and borderline, respectively. Overall psychosocial
      and physical health summary scores were positively correlated with age at
      diagnosis for both groups combined. Those who received CNS radiation therapy (n =
      29) reported significantly worse physical health, but similar psychosocial
      health, compared with those treated without radiation. Neuropsychologic testing
      indicated full-scale and verbal IQ, reading, spelling, and math skills in the
      average range, and performance IQ in the low average range. Intelligence and math
      skills were positively correlated with age at diagnosis. Those with germinomas
      significantly outperformed those with nongerminomatous/ mixed tumors on all
      neuropsychological measures administered. Younger patients diagnosed with CNS
      germ-cell tumors are at increased risk for psychosocial and physical problems as
      well as neuropsychologic deficits. Exposure to irradiation adversely affects
      overall physical functioning, whereas tumor pathology appears to be a salient
      neurocognitive risk factor. Collaborative and randomized studies are required to
      further elucidate the late effects arising from factors such as age at diagnosis,
      tumor histology, level of irradiation therapy, and chemotherapy toxicity among
      these young and potentially curable patients.

PMID- 11465399
TI  - Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical
      resection.
AB  - To describe the clinical features, histologic characteristics, and management of
      patients with pleomorphic xanthoastrocytoma (PXA), we reviewed data on 13
      children who had histologically confirmed PXA and were referred to the neuro
      oncology service between 1985 and 1999. Neuro-imaging with CT and/or MRI
      documented the anatomic location, tumor extent, and degree of resection. There
      were 3 males and 10 females; median age was 12.9 years (range, 8.2-17.2 years).
      The most frequent presentations included seizures (n = 8) and headache (n = 5).
      Tumor sites included temporal (n = 5), parietal (n = 3), frontal (n = 1),
      frontoparietal (n = 1), parietooccipital (n = 1), and temporoparietal (n = 1)
      lobes and the spinal cord (n = 1). CT/MRI revealed a cystic component in 6
      patients, with cyst wall enhancement in 3 patients. The solid component was
      uniformly enhancing in 11 patients. Vasogenic edema was present in 9 patients,
      and calcification was noted in 4 patients. Histopathologic findings included
      meningeal invasion in 12 patients, calcifications in 4, and necrosis in 2.
      Mitotic figures (1-12 per high-power field) were seen in 8 patients. Gross total
      resection was achieved in 8 patients, near total resection in 1, and subtotal
      resection in 4. Ten patients were alive with a median follow-up of 41 months at
      this writing. Two patients died of progressive disease, and 1 died of an
      unrelated cause. In conclusion, pleomorphic xanthoastrocytoma is a rare neoplasm
      in childhood, commonly presenting with seizures. Gross total resection without
      adjuvant therapy provides prolonged disease control, as seen in 6 of 7 patients
      (85%) in our series.

PMID- 11465400
TI  - Limitations of stereotactic biopsy in the initial management of gliomas.
AB  - Stereotactic biopsy is often performed for diagnostic purposes before treating
      patients whose imaging studies highly suggest glioma. Indications cited for
      biopsy include diagnosis and/or the "inoperability" of the tumor. This study
      questions the routine use of stereotactic biopsy in the initial management of
      gliomas. At The University of Texas M. D. Anderson Cancer Center, we
      retrospectively reviewed a consecutive series of 81 patients whose imaging
      studies suggested glioma and who underwent stereotactic biopsy followed by
      craniotomy/resection (within 60 days) between 1993 and 1998. All relevant
      clinical and imaging information was reviewed, including computerized volumetric
      analysis of the tumors based on pre- and postoperative MRI. Stereotactic biopsy
      was performed at institutions other than M. D. Anderson in 78 (96%) of 81
      patients. The majority of tumors were located either in eloquent brain (36 of 81
      = 44%) or near-eloquent brain (41 of 81 = 51%), and this frequently was the
      rationale cited for performing stereotactic biopsy. Gross total resection (>95%)
      was achieved in 46 (57%) of 81 patients, with a median extent of resection of 96%
      for this series. Diagnoses based on biopsy or resection in the same patient
      differed in 40 (49%) of 82 cases. This discrepancy was reduced to 30 (38%) of 80
      cases when the biopsy slides were reviewed preoperatively by each of three
      neuropathologists at M. D. Anderson. Major neurologic complications occurred in
      10 (12.3%) of 81 surgical patients and 3 (3.7%) of 81 patients undergoing biopsy.
      Surgical morbidity was probably higher in our series than it would be for glioma
      patients in general because our patients represent a highly selected subset of
      glioma patients whose tumors present a technical challenge to remove.
      Stereotactic biopsy is frequently inaccurate in providing a correct diagnosis and
      is associated with additional risk and cost. If stereotactic biopsy is performed,
      expert neuropathology consultation should be sought.

PMID- 11465401
TI  - Cell encapsulation technology as a therapeutic strategy for CNS malignancies.
AB  - Gene therapy using viral vectors has to date failed to reveal its definitive
      clinical usefulness. Cell encapsulation technology represents an alternative,
      nonviral approach for the delivery of biologically active compounds to tumors.
      This strategy involves the use of genetically engineered producer cells that
      secrete a protein with therapeutic potential. The cells are encapsulated in an
      immunoisolating material that makes them suitable for transplantation. The
      capsules, or bioreactors, permit the release of recombinant proteins that may
      assert their effects in the tumor microenvironment. During the last decades,
      there has been significant progress in the development of encapsulation
      technologies that comprise devices for both macro- and microencapsulation. The
      polysaccharide alginate is the most commonly used material for cell encapsulation
      and is well tolerated by various tissues. A wide spectrum of cells and tissues
      has been encapsulated and implanted, both in animals and humans, indicating the
      general applicability of this approach for both research and medical purposes,
      including CNS malignancies. Gliomas most frequently recur at the resection site.
      To provide local and sustained drug delivery, the bioreactors can be implanted in
      the brain parenchyma or in the ventricular system. The development of
      comprehensive analyses of geno- and phenotypic profiles of a tumor (genomics and
      proteomics) may provide new and important guidelines for choosing the optimal
      combination of bioreactors and recombinant proteins for therapeutic use.

PMID- 11465402
TI  - Electronic research: an opportunity for the Society for Neuro-Oncology.

PMID- 11465403
TI  - The autopsy: obtaining quality assurance of treatment.

PMID- 11465404
TI  - Altered diltiazem metabolism in the neonatal rabbit following intra-uterine
      chronic exposure to diltiazem.
AB  - 1. Diltiazem undergoes extensive metabolism in hepatic and extrahepatic tissues.
      Deacetyldiltiazem (M1) and N-demethyldiltiazem (MA) are two of the main basic
      metabolites of diltiazem that retain pharmacological activity. This drug impairs
      its own metabolism after chronic administration in the adult patient. The study
      examines the possibility that intra-uterine exposure following chronic maternal
      therapy with DTZ from mid-gestation to term also impairs DTZ metabolism of its
      offspring. 2. DTZ was incubated in homogenates from liver, lung, brain and gut
      and in the whole blood of animals whose mothers were exposed to chronic treatment
      with diltiazem or unexposed (placebo). DTZ and its metabolites were assayed by
      HPLC. 3. DTZ deacetylase activity observed in liver, lung and brain homogenates
      from 1-, 8- and 16-day-old rabbits was significant lower in exposed animals. In
      gut homogenates, this age-dependent effect was not so clear. This inhibition
      could not be detected in any organ of 30-day-old rabbits. On the other hand, the
      activity observed in whole blood was not altered by intra-uterine chronic
      exposure to DTZ. 4. DTZ demethylase activity showed no differences in tissue
      homogenates and in whole blood from exposed compared with the unexposed rabbit.
      5. In conclusion, the findings suggest that intra-uterine chronic exposure to DTZ
      has a large and prolonged effect on newborn metabolism deacetylase activity
      compared with the unexposed rabbit.

PMID- 11465405
TI  - Metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin by
      human hepatic CYP isoforms: evidence for selectivity towards CYP3A4.
AB  - 1. The metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4
      trifluoromethylcoumarin (BFBFC) to 7-hydroxy-4-trifluoromethylcoumarin (HFC) was
      studied in human liver microsomes and in cDNA-expressed human liver CYP isoforms.
      For purposes of comparison, some limited studies were also performed with 7
      benzyloxyquinoline (7BQ). 2. Initial interactive docking studies with a homology
      model of human CYP3A4 indicated that BFBFC was likely to be a selective substrate
      for CYP3A4 with a relatively high binding affinity, due to the presence of
      several key hydrogen bonds with active site amino acid residues. 3. Kinetic
      analysis of NADPH-dependent BFBFC metabolism to HFC in three preparations of
      pooled human liver microsomes revealed mean (+/- TSEM) Km and Vmax = 4.6 +/- 0.3
      microM and 20.0 +/- 3.8 pmol/min/mg protein, respectively. 4. The metabolism of
      BFBFC to HFC was determined in a characterized bank of 24 individual human liver
      microsomal preparations employing a BFBFC substrate concentration of lO microM
      (i.e. around twice Km). Good correlations (r2 = 0.736-0.904) were observed
      between BFBFC metabolism and markers of CYP3A isoforms. 5. While 10O microM BFBFC
      was metabolized to HFC by cDNA-expressed CYP3A4, little or no metabolism was
      observed with cDNA-expressed CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19,
      CYP2D6 and CYP2E1. 6. The metabolism of 10 microM BFBFC in human liver microsomes
      was markedly inhibited by 5-50 microM troleandomycin and 0.2-5 microM
      ketoconazole, but stimulated by 0.2-10 microM alpha-naphthoflavone. The
      metabolism of 10 microM BFBFC in human liver microsomes was also markedly
      inhibited by an antibody to CYP3A4. 7. Kinetic analysis of NADPH-dependent 7BQ
      metabolism to 7-hydroxyquinoline (7HQ) in human liver microsomes revealed Km and
      Vmax = 70 microM and 3.39 nmol/min/mg protein, respectively. 8. While 80 microM
      7BQ was metabolized to 7HQ by cDNA-expressed CYP3A4, only low rates of metabolism
      were observed with cDNA-expressed CYPIA2, CYP2A6, CYP2B6, CYP2C8, CYP2C9,
      CYP2C19, CYP2D6 and CYP2E1. 9. In summary, by correlation analysis, the use of
      cDNA-expressed CYP isoforms, chemical inhibition and inhibitory antibodies, BFBFC
      metabolism in human liver microsomes appears to be primarily catalysed by CYP3A4.
      BFBFC may be a useful fluorescent probe substrate for human hepatic CYP3A4, but
      compared with 7BQ has only a low rate of metabolism in human liver microsomes.

PMID- 11465406
TI  - Microsomal metabolism of the terpene 1,8-cineole in the common brushtail possum
      (Trichosurus vulpecula), koala (Phascolarctos cinereus), rat and human.
AB  - 1. This study reports on the pathways of metabolism and enzyme kinetics of the
      Eucalyptus terpene, 1,8-cineole, by liver microsomes from the brushtail possum
      (Trichosurus vulpecula) and koala (Phascolarctos cinereus) (animals that normally
      include this terpene in their diet), rat and human. 2. The rank order of the
      ability to metabolize 1,8-cineole with respect to overall 1,8-cineole intrinsic
      clearance (CL'int = Vmax/Kmax in microl mg protein(-1) min(-1)) was koala (188) >
      possum (181)>> rat (28) > human (12). This order supports the hypothesis that
      adaptation to a Eucalyptus diet involves enhanced metabolism of terpenes. 3. The
      metabolism of 1,8-cineole was also studied in the liver from brushtail possum
      pretreated with a mixture of terpenes, which have previously been shown to induce
      cytochrome P450 enzymes. Rats were pretreated with the same mixture of terpenes
      or phenobarbitone. 4. Terpene pretreatment more than doubled the CL'int of 1,8
      cineole by brushtail possum liver microsomes (from 180 to 394 microl mg protein(
      1) min(-1)) and increased rat CL'int by nearly 10-fold (from 28 to 259 microl mg
      protein(-1) min(-1)), but still less than the induced possum value. However,
      phenobarbitone had the greatest inducing effect, increasing the rat CL'int to
      1,825 microl mg protein(-1) min(-1). 5. A regioselective preference of oxidation
      was evident between adapted and non-adapted species. In rat and human oxidation
      was preferred at the aliphatic ring carbons over methyl substituents. In possum,
      many of the available carbons were utilized, however metabolism at methyl
      substituents was preferred. In the koala, oxidation occurred primarily at the
      methyl substituents.

PMID- 11465407
TI  - Different expression of hepatic and renal cytochrome P450s between the
      streptozotocin-induced diabetic mouse and rat.
AB  - 1. Since limited information is available about alterations of cytochrome P450
      levels in diabetic animals other than rat, expression of P450s in the liver and
      kidney of the streptozotocin (STZ)-induced diabetic mouse was investigated. 2.
      The mRNA levels of CYP2B10, 3A11, 4A10 and 4A14 in the liver were increased in
      the STZ-induced diabetic mouse of both sexes. The CYP2B9 mRNA level was increased
      in the liver of the male diabetic mouse. These alterations were observed even at
      2 weeks after administration. Insulin treatment restored these changes. The
      findings were consistent with changes reported in rat. 3. The levels of hepatic
      CYP1A2 and 2E1 and renal 2E1 and 4A did not change in the diabetic mouse at any
      time-point examined. No changes were seen in CYP2A- or 2C-related proteins in the
      diabetic mouse. These findings were in contrast to those in rat. 4. The results
      indicate that mouse P450s respond to insulin-dependent diabetes mellitus
      differently from those of the rat, and suggest that the expression of P450s in
      diabetes is not generally the same across animal species.

PMID- 11465408
TI  - Colonic drug delivery: prodrug approach.
AB  - The colon is largely being investigated as a site for administration of protein
      and peptides, which are degraded by digestive enzymes in the upper GIT. Also for
      local diseases of the colon, drug administration to the site of action can not
      only reduce the dose to be administered, but also decrease the side effects. One
      of the approaches used for colon specific drug delivery is the formation of a
      prodrug which optimizes drug delivery and improves drug efficacy. Many prodrugs
      have been evaluated for colon drug delivery. These prodrugs are designed to pass
      intact and unabsorbed from the upper GIT and undergo biotransformation in the
      colon releasing the active drug molecule. This biotransformation is carried out
      by a variety of enzymes, mainly of bacterial origin present in the colon (e.g.
      azoreductase, glucuronidase, glycosidase, dextranase, esterase, nitroreductase,
      cyclodextranase, etc.). The present review includes varius prodrug approaches
      investigated for colon drug delivery and their site specificity.

PMID- 11465409
TI  - Expression of multidrug resistance-associated protein (MRP) in human retinal
      pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase
      inhibitor.
AB  - PURPOSE: The objective of this study was to determine the expression and activity
      of multidrug resistance-associated protein (MRP) in the retinal pigment
      epithelial (RPE) cells and to further assess whether BAPSG, a novel anionic
      aldose reductase inhibitor, interacts with MRP. METHODS: Functional and
      biochemical evidence for MRP was obtained in a human retinal pigment epithelial
      (ARPE-19) cell line and primary cultures of human retinal pigment epithelial
      (HRPE) cells. Fluorescein accumulation and efflux in the presence and absence of
      MRP inhibitors was used to obtain functional evidence for MRP. Western blots and
      RT-PCR were used to obtain biochemical evidence for MRP1. The influence of MRP
      inhibitors on BAPSG accumulation and efflux in ARPE-19 cells was determined to
      understand its interaction with MRP. RESULTS: MRP inhibitors increased
      fluorescein accumulation and reduced efflux in RPE cells. Both cell types
      exhibited a 190-kDa western blot band corresponding to MRP1 protein and a 287 bp
      RT-PCR band corresponding to MRP1 mRNA. MRP inhibitors reduced BAPSG efflux and
      increased its accumulation in ARPE-19 cells. CONCLUSIONS: MRP is functionally and
      biochemically active in human RPE cells. Anionic BAPSG is a likely substrate for
      MRP.

PMID- 11465410
TI  - Transport of levofloxacin in the OK kidney epithelial cell line: interaction with
      p-aminohippurate transport.
AB  - PURPOSE: To evaluate the mechanism of renal transport of quinolone antibacterial
      drugs, we examined the interaction of levofloxacin with p-aminohippurate (PAH)
      transport systems and the transport of levofloxacin in renal epithelial cells.
      METHODS: Transport of [14C]PAH or [14C]levofloxacin was measured using OK cell
      monolayers grown on microporous membrane filters. RESULTS: Transcellular
      transport from the basolateral to the apical side and cellular accumulation of
      [14C]PAH were inhibited by levofloxacin. Both the initial uptake of [14C]PAH from
      the basolateral side and the efflux to the apical side were inhibited by
      levofloxacin. The basolateral-to-apical transcellular transport of
      [14C]levofloxacin was greater than that in the opposite direction.
      [14C]Levofloxacin efflux to the apical side was greater than that to the
      basolateral side. Unlabeled levofloxacin and grepafloxacin inhibited the
      transcellular transport of [14C]levofloxacin, accompanied by an increase of
      cellular accumulation. However, neither PAH nor an anion transport inhibitor 4-4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) affected the basolateral-to
      apical transport of [14C]levofloxacin nor its uptake from the basolateral side.
      CONCLUSIONS: These results indicated that levofloxacin inhibits PAH transport
      across both the basolateral and apical membranes of OK cells, but are not
      transported via the systems for PAH transport. The existence of a specific
      transport system for quinolones was indicated in OK cells.

PMID- 11465411
TI  - Physicochemical parameters responsible for the affinity of methotrexate analogs
      for rat canalicular multispecific organic anion transporter (cMOAT/MRP2).
AB  - PURPOSE: Canalicular multispecific organic anion transporter (cMOAT/MRP2) is
      known to exhibit a broad substrate specificity toward amphiphatic organic anions,
      including methotrexate (MTX). The present study aims to identify the
      physicochemical properties of MTX derivatives that correlate with recognition
      specificity by cMOAT/MRP2. METHODS: We examined the inhibitory effect of MTX and
      24 analogs on the transport of [3H]-S-(2,4-dinitrophenyl)glutathione by
      cMOAT/MRP2. The affinity constants of these compounds were compared with their
      physicochemical parameters. The primary active transport of several compounds was
      also confirmed. RESULTS: The affinity constants closely correlated with the
      octanol/water partition coefficient (clogP), and a linear combination of polar
      and nonpolar surface areas. The affinity for cMOAT/MRP2 also closely correlated
      with the molecular weight, which also showed a significant correlation with
      nonpolar surface area and clogP. CONCLUSIONS: Recognition by cMOAT/MRP2 depends
      on a balance of dynamic surface properties between the polar and nonpolar regions
      of MTX analogs. The so-called "molecular weight threshold" for the cMOAT/MRP2
      affinity of these compounds can be explained by their physicochemical parameters,
      especially their nonpolar surface areas.

PMID- 11465412
TI  - P-glycoprotein inhibition leads to enhanced disruptive effects by anti
      microtubule cytostatics at the in vitro blood-brain barrier.
AB  - PURPOSE: To investigate whether P-glycoprotein (Pgp) protects the in vitro BBB
      against the cytotoxic effects of anti-tumour drugs. METHODS: In an in vitro BBB
      coculture model the influence of the anti-microtubule drugs vinblastine,
      colchicine, paclitaxel and the non-anti-microtubule drugs doxorubicin,
      fluorouracil and etoposide in the absence or presence of Pgp modulators on the
      trans-endothelial electrical resistance (TEER), which is an indicator for the
      integrity, was investigated. RESULTS: In the absence of Pgp modulators
      vinblastine, colchicine and paclitaxel dose dependently decreased TEER values to
      less than 20% of control. Non-anti-microtubule drugs did not affect TEER values.
      Following competitive inhibition of Pgp by various Pgp modulators and substrates,
      even low concentrations of vinblastine, colchicine and paclitaxel substantially
      decreased TEER. IC50 values of LY 335979, SDZ-PSC 833, cyclosporin A, and
      verapamil were 0.03, 0.25, 0.46, and 13.7 microM, respectively. CONCLUSIONS:
      These results indicate that Pgp normally protects the in vitro BBB against the
      disruptive effects of anti-microtubule drugs, but its integrity is lost when anti
      microtubule drugs are used in combination with potent Pgp modulators. In
      addition, this procedure offers the possibility to characterize Pgp modulators
      and substrates with respect to their efficacy and to elucidate drug interactions
      at the level of Pgp.

PMID- 11465413
TI  - Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic
      model drug assessed by microdialysis and pharmacodynamics.
AB  - PURPOSE: The aim of the study was to investigate the cutaneous bioequivalence of
      a lipophilic model drug (lidocaine) applied in a novel topical microemulsion
      vehicle, compared to a conventional oil-in-water (O/W) emulsion, assessed by a
      pharmacokinetics microdialysis model and a pharmacodynamic method. METHODS:
      Dermal delivery of lidocaine was estimated by microdialysis in 8 volunteers.
      Absorption coefficients and lag times were determined by pharmacokinetic
      modelling of the microdialysis data. Subsequently, the anaesthetic effect of the
      treatments was assessed by mechanical stimuli using von Frey hairs in 12
      volunteers. RESULTS: The microemulsion formulation increased the cutaneous
      absorption coefficient of lidocaine 2.9 times (95% confidence interval: 1.9/4.6)
      compared with the O/W emulsion-based cream. Also, lag time decreased from 110 +/-
      43 min to 87 +/- 32 min (P = 0.02). The compartmental pharmacokinetic model
      provided an excellent fit of the concentration-time curves with reliable
      estimation of absorption coefficient and lag time. A significant anaesthetic
      effect was found for both active treatments compared to placebo (P < 0.02), but
      the effect did not diverge significantly between the two formulations.
      CONCLUSIONS: The microemulsion vehicle can be applied to increase dermal drug
      delivery of lipophilic drugs in humans. The microdialysis technique combined with
      an appropriate pharmacokinetic model provides a high sensitivity in
      bioequivalence studies of topically applied substances.

PMID- 11465414
TI  - Synthesis, in vitro skin permeation studies, and PLS-analysis of new naproxen
      derivatives.
AB  - PURPOSE: To synthesize new naproxen (01) derivatives with amide or ester
      structures or with a combination of the two (02-15). To compare their
      physicochemical properties with naproxen esters (16-22) and their respective skin
      permeation behavior. To study structure-permeation relationships via partial
      least squares (PLS)-analysis. METHODS: Stability, aqueous, and octanol solubility
      were determined. Lipophilicity and further 53 chemical descriptors were computed.
      A suitable in-vitro skin permeation model was developed to compare maximal flux
      (Jmax) of derivatives. Based on these flux data, PLS-analysis was performed to
      derive structure-permeation relationships. RESULTS: None of the new derivatives
      showed an improved flux in comparison to naproxen. This result can be explained
      by PLS-analysis: skin permeation increases with the solubility both in water and
      in octanol. For a good permeation, an optimized molecule should exhibit a small
      volume with a spherical shape. The surface area should be large in relation to
      volume, as indicated by the rugosity parameter. A clear separation between the
      hydrophobic and the hydrophilic domain (= high amphiphilic moment) is favorable.
      Lipophilicity is inversely correlated with skin permeation. CONCLUSIONS: PLS
      analysis is a valuable tool to derive significant, internally predictive
      quantitative models for structure-permeation relationships of naproxen
      derivatives in the above described skin permeation assay.

PMID- 11465415
TI  - Mutual inhibition of the insulin absorption-enhancing properties of
      dodecylmaltoside and dimethyl-beta-cyclodextrin following nasal administration.
AB  - PURPOSE: To determine if a nasal insulin formulation containing two distinct
      absorption-enhancing agents exhibits an additive or synergistic increase in the
      rate of systemic insulin absorption. METHODS: The pharmacokinetics and
      pharmacodynamics of insulin absorption were measured in hyperglycemic
      anesthetized rats following nasal insulin administration with formulations
      containing two different types of absorption-promoting agents, dimethyl-beta
      cyclodextrin (DMBCD) and dodecylmaltoside (DDM). RESULTS: When either DDM (0.1
      0.5%) or DMBCD (1.0-5.0%) was added to the nasal insulin formulation, a
      significant and rapid increase in plasma insulin levels was observed, with a
      concomitant decrease in blood glucose concentration. A combined preparation
      containing 0.25% DDM (0.005 M) and 2.5% DMBCD (0.019M), however, failed to cause
      an increase in plasma insulin levels or a decrease in blood glucose
      concentration. Increasing concentrations of DDM added to an insulin formulation
      with a fixed DMBCD concentration caused a decrease, rather than an increase, in
      systemic absorption of insulin. CONCLUSIONS: Mixing DMBCD and DDM resulted in
      mutual inhibition of their ability to enhance systemic absorption of insulin
      following nasal delivery. The results are consistent with the formation of an
      inclusion complex between DDM and DMBCD which lacks the ability to enhance nasal
      insulin absorption.

PMID- 11465416
TI  - CYP2C19 genotype related effect of omeprazole on intragastric pH and
      antimicrobial stability.
AB  - PURPOSE: A combination of proton pump inhibitors and antimicrobials has been
      applied as an anti-Helicobacter pylori (H. pylori) therapy. Omeprazole, one of
      the proton pump inhibitors, is metabolized by CYP2C19. which exhibits genetic
      polymorphism. It was reported previously that the overall anti-H. pylori efficacy
      can be related to the CYP2C19 genotype. The main aim of the present study was to
      obtain a rational explanation for the relationship between the overall anti-H.
      pylori efficacy and the CYP2C19 genotype. METHODS: Six healthy volunteers were
      classified as extensive metabolizers and poor metabolizers, according to their
      CYP2C19 genotypes. Plasma concentrations and intragastric pH were monitored prior
      to and until 24 h after the administration of 20 mg omeprazole. The stability of
      amoxicillin, clarithromycin, and metronidazole was examined using buffer
      solutions with monitored intragastric pH, and their remaining percentage in the
      intragastric space was simulated. RESULTS: The poor metabolizers, classified by
      the CYP2C19 genotypes, showed the higher effectiveness in anti-H. pylori therapy,
      via the higher plasma concentration of omeprazole and the higher intragastric pH,
      and possibly the higher stability of antimicrobials in the higher intragastric
      pH. CONCLUSIONS: CYP2C19 genotyping is a very useful method to determine the
      effective and safe dosage regimen including the selection of the dual and triple
      therapy in anti-H. pylori therapy.

PMID- 11465417
TI  - Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and
      prediction of in vivo drug-drug interactions.
AB  - PURPOSE: To evaluate an interaction between simvastatin and itraconazole in in
      vitro studies and to attempt a quantitative prediction of in vivo interaction in
      humans. METHODS: The inhibitory effect of itraconazole on simvastatin metabolism
      was evaluated using human liver microsomes and the Ki values were calculated for
      the unbound drug in the reaction mixture. A physiologically-based pharmacokinetic
      model was used to predict the maximum in vivo drug-drug interaction. RESULTS:
      Itraconazole competitively inhibited the metabolism of simvastatin to M-1 and M-2
      with Ki values in the nM range. The area under the curve (AUC) of simvastatin
      after concomitant dosing with itraconazole was predicted to increase ca. 84-101
      fold compared with that without administration of itraconazole. Taking into
      consideration the fact that this method predicts the maximum interaction, this
      agrees well with the clinical observation of a 19-fold increase. A similar
      prediction, based on the Ki value without taking into account the drug adsorption
      to microsomes, led to an underevaluation of the interaction. CONCLUSIONS: It was
      demonstrated that the competitive inhibition of CYP3A4-mediated simvastatin
      metabolism by itraconazole is the main cause of the drug interaction and that a
      Ki value corrected for drug adsorption to microsomes is the key factor in
      quantitatively predicting the maximum in vivo drug interactions.

PMID- 11465418
TI  - Effect of oxidative stress on the structure and function of human serum albumin.
AB  - PURPOSE: Human serum albumin (HSA) was mildly oxidized by a metal-catalyzed
      oxidation system (MCO-HSA), chloramine-T (CT-HSA) or H2O2 (H2O2-HSA), and the
      effects of these treatments on the structural, drug-binding and esterase-like
      properties were studied. METHODS: Protein conformation was examined by
      calorimetric, chromatographic, electrophoretic and spectroscopic techniques. Drug
      binding was studied by ultrafiltration method, and esterase-like activity was
      determined using p-nitrophenyl acetate as a substrate. RESULTS: Far-UV and near
      UV CD spectra indicated that significant structural changes had occured as the
      result of treatment with MCO-HSA and CT-HSA but not with H2O2-HSA. However, SDS
      PAGE analysis does not provide precise information on gross conformational
      changes such as fragmentation, cross-linking and SDS-resistant polymerisation.
      The results of differential scanning calorimetry, the fluorescence of the
      hydrophobic probe 1,1-bis-4-anilino-naphthalene-5,5-sulfonic acid and the elution
      time from a hydrophobic HPLC column indicated that MCO-HSA and CT-HSA in
      particular, have a more open structure and a higher degree of exposure of
      hydrophobic areas than unoxidized HSA. In all cases, high-affinity binding of
      warfarin remained unchanged for all the oxidized HSAs. However, high-affinity
      binding of ketoprofen to CT-HSA and, especially, MCO-HSA was diminished. In
      addition, the esterase-like activity of these proteins were all decreased to the
      same low level. CONCLUSIONS: Mild oxidation of HSA has no detectable effect on
      the binding of drugs to site I in subdomain IIA. In contrast, both the ligand
      binding property of site II and the esterase-like activity of oxidized HSAs are
      decreased, most probably due to conformational changes in subdomain IIIA.

PMID- 11465419
TI  - Development of systems for targeting the regional lymph nodes for diagnostic
      imaging: in vivo behaviour of colloidal PEG-coated magnetite nanospheres in the
      rat following interstitial administration.
AB  - PURPOSE: Nanoparticles can be utilised for targeting drugs to the regional lymph
      nodes or as diagnostic agents. The surface modification of magnetite nanospheres
      with poly(ethylene glycol) (PEG) has been assessed by in vitro characterisation
      and in vivo studies following subcutaneous administration to the rat. METHODS:
      Magnetite nanospheres were prepared with a grafted PEG layer using various PEG
      lengths from 350 to 1,000 Da. Thermogravimetric analysis was utilised to measure
      the adsorbed amount of PEG. Colloid stability was confirmed by measurement of the
      particle size and electrophoretic mobility. The kinetics of injection site
      drainage and lymph node retention were determined 2 hours after subcutaneous
      administration, for nanospheres coated with PEG lengths of 350, 550. 750, and
      1,000 Da. For the 750 PEG coated nanospheres, the kinetics of distribution was
      determined over a 48-hour time course. RESULTS: The distribution of the
      nanospheres was modified and the lymph node localisation enhanced by altering the
      surface coverage of PEG on the magnetic surface. CONCLUSIONS: PEG-coated
      magnetite nanospheres with different surface characteristics can be utilised to
      target a diagnostic agent to regional lymph nodes.

PMID- 11465420
TI  - Relationship between physicochemical and osteotropic properties of bisphosphonic
      derivatives: rational design for osteotropic drug delivery system (ODDS).
AB  - PURPOSE: The objective of this investigation is to develop a rational design of
      Osteotropic Drug Delivery System (ODDS), which we have proposed as a novel method
      for drug delivery to the skeleton via bisphosphonic prodrug, based on the
      relationship between physicochemical and pharmacokinetic properties of
      bisphosphonates. METHODS: The theoretical octanol/water partition coefficients
      (clog P) of 13 bisphosphonates were calculated by computer software, CLOGP ver.
      3.05 (Daylight C.I.S., Inc. Irvine, CA) and related to pharmacokinetic or
      osteotropic parameters after intravenous injection into rats. On the other hand,
      to optimize ODDS of diclofenac (DIC-BP), the effects of doses or infusion rates
      on the in vivo disposition were investigated in relation to solubility product
      value (Ksp) of DIC-BP-calcium complex. RESULTS: Clog P had good correlations with
      total plasma clearance, apparent distribution volume and the fraction dose
      delivered to the whole skeleton after bolus injection into rats (r = -0.868
      approximately -0.914). The targetability of bisphosphonates to the skeleton was
      linearly decreased with an increase in clog P value and the more hydrophilic
      bisphosphonates were suitable for ODDS in bolus administration. On the other
      hand, DIC-BP, a relatively lipophilic bisphosphonate, was effectively and
      selectively delivered to the skeleton only when administered as a slow infusion
      to keep plasma concentration lower than that calculated from Ksp value where DIC
      BP could precipitate with calcium in the plasma circulation. CONCLUSIONS: Our
      results suggest the possibility of a rational design of ODDS via bisphosphonic
      prodrugs, after consideration of compound lipophilicity and precipitability of
      bisphosphonate-calcium complex.

PMID- 11465421
TI  - Development of a generalized, quantitative physicochemical model of CYP3A4
      inhibition for use in early drug discovery.
AB  - PURPOSE: To examine the structure-activity relationships for the inhibition of
      the activity of recombinant human CYP3A4 and to establish a generalized,
      quantitative physicochemical model for use in early drug discovery. METHODS:
      Inhibition of the activity of recombinant human CYP3A4 (erythromycin N
      demethylase) by 30 diverse chemicals was studied using enhanced throughput
      methodology. RESULTS: There was a general, strong correlation between the IC50
      value determined against erythromycin N-demethylase activity and lipophilicity
      (LogD7.4) (r2 = 0.68, p <0.0001). This relationship was strengthened further by
      subdividing the structures studied into two distinct subpopulations of chemistry
      within the dataset. These could be identified by the absence (r2 = 0.80, p
      <0.0001) or presence (r2 = 0.69, p <0.0001) of a sterically uninhindered N
      containing heterocycle, more specifically a pyridine, imidazole, of triazole
      function. The presence of these structural motifs increased the potency of CYP3A4
      inhibition by approximately 10-fold for a given lipophilicity (LogD7.4.value).
      More detailed analyses of AstraZeneca compounds demonstrated that the inhibitory
      potency of the pyridine structure can be attenuated through direct steric effects
      or electronic substitution resulting in a modulation of the pKa of the pyridine
      nitrogen, thereby influencing its ability to interact with the CYP heme.
      CONCLUSIONS: A generalized, quantitative model is proposed for the inhibition of
      the major drug metabolizing enzyme, CYP3A4. This model indicates the importance
      of lipophilicity and rationalizes increased potency arising through additional
      interactions with the heme iron. These general relationships were shown to be
      applicable to a selection of compounds of interest to several early research
      projects.

PMID- 11465422
TI  - SEM imaging predicts quality of niosomes from maltodextrin-based proniosomes.
AB  - PURPOSE: The limits to surfactant loading of proniosomes were determined and a
      rationale developed for the observed relationship between the composition of
      proniosomes and the quality of reconstituted niosome suspension. METHODS: A novel
      method for producing proniosomes with a maltodextrin carrier was recently
      developed, which provides for rapid reconstitution of niosomes with minimal
      residual carrier. A slurry of maltodextrin and surfactant was dried to form a
      free-flowing powder which could be rehydrated by addition of warm water. This
      method provided facile production of a wide range of proniosome compositions, and
      thus, allowed us to examine rehydration behavior for similar concentrations of
      surfactant over a wide range of film thickness. SEM images of proniosomes with
      various degrees of surfactant loading and images of pure surfactant were
      compared. Direct observation and particle size measurements by laser light
      scattering provided characterization of the final niosome preparations. RESULTS:
      Successful rehydration of surfactant to produce niosomes from dried film requires
      that the film be as thin as possible to avoid the clumping and precipitation that
      occurs when pure, granular surfactant is hydrated directly. The appearance of a
      coarse, broken surface on the proniosomes correlates with inefficient rehydration
      and occurrence of aggregation and precipitate in the final niosome suspension.
      CONCLUSIONS: These observations provide an indication of the requirements for dry
      proniosomes to yield niosome suspensions of high quality.

PMID- 11465423
TI  - The use of inverse phase gas chromatography to measure the surface energy of
      crystalline, amorphous, and recently milled lactose.
AB  - PURPOSE: To assess differences in surface energy due to processing induced
      disorder and to understand whether the disorder dominated the surfaces of
      particles. METHODS: Inverse gas chromatography was used to compare the surface
      energies of crystalline, amorphous, and ball milled lactose. RESULTS: The milling
      process made ca 1% of the lactose amorphous, however the dispersive contribution
      to surface energy was 31.2, 37.1, and 41.6 mJ m(-2) for crystalline, spray dried
      and milled lactose, respectively. A physical mixture of crystalline (99%) and
      amorphous (1%) material had a dispersive surface energy of 31.5 mJ m(-2).
      CONCLUSION: Milling had made the surface energy similar to that of the amorphous
      material in a manner that was very different to a physical mixture of the same
      amorphous content. The milled material will have similar interfacial interactions
      to the 100% amorphous material.

PMID- 11465424
TI  - Effect of cyclodextrin charge on complexation of neutral and charged substrates:
      comparison of (SBE)7M-beta-CD to HP-beta-CD.
AB  - PURPOSE: To understand the role of charge in substrate/cyclodextrin complexation
      by comparing the binding of neutral and charged substrates to a neutral
      cyclodextrin, such as hydroxypropyl beta-CD (HP-beta-CD) with 3.5 degrees of
      substitution, and an anionically charged cyclodextrin, such as sulfobutyl ether
      beta-CD ((SBE)7M-beta-CD) with 6.8 degrees of substitution. METHOD: HP-beta-CD
      and (SBE)7M-beta-CD were evaluated in their ability to form inclusion complexes
      with neutral compounds, as well as to cationic and anionic substrates in their
      charged and uncharged forms. The complexation constants (Kc) were determined via
      a UV spectrophotometric technique, by monitoring the change in substrate
      absorbance upon incremental addition of a concentrated cyclodextrin solution. The
      role of electrostatic interaction was probed by observing Kc as a function of
      solution ionic strength. RESULTS: Neutral molecules displayed a stronger
      interaction with (SBE)7M-beta-CD compared to HP-beta-CD. In those cases where the
      guest possessed a charge (positive or negative), HP-beta-CD/substrate complexes
      exhibited a decrease in complexation strength (2 to 31 times lower) compared to
      the neutral forms of the same substrate. The same was true (but to a larger
      extent, 41 times lower) for negatively charged molecules binding to (SBE)7M-beta
      CD due to charge-charge repulsion. However, positively charged molecules
      interacting with the negatively charged (SBE)7M-beta-CD displayed a similar
      binding capability as their neutral counterpart, due to charge-charge attraction.
      Further evaluation through manipulation of solution ionic strength revealed
      strong electrostatic interactions between substrate and cyclodextrin charges. In
      addition, the studies suggested that on average two sulfonates out of seven may
      be involved in forming ionic attraction or repulsion effects with the positive
      charges on prazosin and papaverine, or negative charges of ionized naproxen and
      warfarin. CONCLUSIONS: Presence of charge on the cyclodextrin structure provides
      an additional site of interaction compared to neutral cyclodextrins, which may be
      modified using solution ionic strength.

PMID- 11465425
TI  - Microhardness and dislocation identification studies on paracetamol single
      crystals.
AB  - PURPOSE: To study the mechanical behaviour of paracetamol single crystals.
      METHODS: Microhardness indentation techniques were used to study the hardness
      anisotropy of paracetamol. Solvent etching technique was used to define the range
      of plastic deformation and the orientation of the dislocation lines. The
      orientation dependence of Knoop hardness on the (001), (110) and (201) surfaces
      was compared with calculated values of the Effective Resolved Shear Stress (ERSS)
      for plastic deformation by specific dislocation types. RESULTS: The principal
      habit faces of single crystals using both Vickers and Knoop indenters showed a
      range of hardness from 235 to 456 MPa depending on the type of indenter used and
      its orientation on the surface. Solvent etching of the plastically deformed
      region of the crystal around the Vickers/Knoop indentations confirmed that the
      slip plane was (010). ERSS analysis suggested that the deformation occurred by
      the slip of dislocations of the types (010)[001] and (010)[100]. Crystals doped
      with 0.08-0.8 w/w% p-acetoxyacetanilide showed hardness values similar to the
      pure material. CONCLUSIONS: The low number of distinct dislocation slip systems
      (two) is characteristic of a brittle material and is consistent with the
      observation that paracetamol will tolerate only deformations of 1 part in 10(6)
      before fracture.

PMID- 11465426
TI  - Polymorph control of sulfathiazole in supercritical CO2.
AB  - PURPOSE: Sulfathiazole was used to investigate polymorph control in liquid and
      supercritical CO2. Conventional techniques require a variety of solvents and
      techniques to produce different polymorphs. The present approach involves
      precipitation from an organic solution with liquid or supercritical CO2 using the
      SEDS process. METHODS: Sulfathiazole was precipitated from methanol or acetone
      solutions. Experiments were carried out within a temperature range of 0-120
      degrees C. Composition of the fluid phase was varied between x(CO2) = 0.27-0.99.
      Pressure was constant at 200 bar. Samples obtained were analyzed using SEM, DSC,
      and XRPD. RESULTS: Pure polymorphs were obtained at different temperatures and
      flow rate ratios of CO2/solvent. With methanol Form I, III, and IV and their
      mixtures could be crystallized. With acetone Form I or a mixture of Form I and
      amorphous sulfathiazole was obtained. The fluid composition was used as a control
      parameter to define the process areas (T-x diagram) where the pure forms or
      mixtures of different forms could be obtained. CONCLUSIONS: The experiments
      enabled the relationship between flow and temperature for each polymorph to be
      determined. The crystallization method developed proved to be a simple and
      efficient technique for reproducible and consistent isolation of sulfathiazole
      polymorphs.

PMID- 11465427
TI  - Study of the breakup under shear of a new thermally reversible water-in-oil-in
      water (W/O/W) multiple emulsion.
AB  - PURPOSE: Thickening of the external aqueous phase of W/O/W multiple emulsions is
      essential to increase the release under shear. However, it leads to globules
      bursting during fabrication. To reduce this problem, we have tested a novel
      thermally reversible hydrogel, EMP hydrogel. This way, the corresponding multiple
      emulsion (EMPME) would gel only at skin temperature, which may increase the
      active ingredient delivery when topically applied. METHODS: Samples were sheared
      at different shear rates and temperatures (20, 30, and 35 degrees C) with a
      controlled rheometer. A granulometric analysis was then performed with a laser
      diffraction granulometer, to assess the break up as a function of the shear rate
      at the three temperatures. Conductometric measurements (CDM 230 conductometer)
      provided the corresponding release curves. RESULTS: As we expected, EMPME
      exhibited a thermally reversible behavior. Compared to a reference emulsion
      thickened by carbopol, this new thermo-sensitive multiple emulsion displayed
      higher break up and fraction released at 35 degrees C. CONCLUSION: The first
      thermally reversible multiple emulsion has been developed in the present work.
      This one presents interesting advantages: (1) an easy fabrication process with a
      higher entrapment yield and (2) a higher fraction released at 35 degrees C
      compared with the reference emulsion.

PMID- 11465428
TI  - Lipophilicity behaviour of the Zwitterionic antihistamine cetirizine in
      phosphatidylcholine liposomes/water systems.
AB  - PURPOSE: The partitioning of cetirizine in a phosphatidylcholine liposomes/water
      system was compared with that of hydroxyzine and acrivastine to gain insight into
      the mechanisms of interaction of its various electrical species with membranes.
      METHODS: The lipophilicity profiles of the compounds were obtained from
      equilibrium dialysis and potentiometry, and compared with changes in NMR
      relaxation rates. RESULTS: The neutral form of hydroxyzine interacted mainly via
      hydrophobic interactions with the bilayer lipid core of the membrane, whereas for
      the cationic form both hydrophobic and electrostatic interactions were involved.
      Zwitterionic and anionic cetirizine were less lipophilic than its cation, which
      behaved like the corresponding species of hydroxyzine. Zwitterionic cetirizine
      interacted more by weak electrostatic interactions with the polar headgroups of
      phospholipids than by hydrophobic interactions with the membrane interior. The
      lipophilicity of its anion reflected the balance of repulsive electrostatic
      interactions between the carboxylate and phosphate groups and the hydrophobic
      interactions with the lipid core. CONCLUSION: The study confirms that various
      mechanisms influence the interaction of solutes with liposomes. Combining
      experimental techniques and using suitable reference compounds proves useful.

PMID- 11465429
TI  - The apparent lipophilicity of quaternary ammonium ions is influenced by galvani
      potential difference, not ion-pairing: a cyclic voltammetry study.
AB  - PURPOSE: This work examines whether ion-pairing contributes to the apparent
      lipophilicity of cations, which is seen by a shake-flask or titrimetic method to
      be influenced by the nature and concentration of counter-ions. METHODS: To solve
      this problem, the lipophilicity of several quaternary ammonium drugs was measured
      by cyclic voltammetry in the 1,2-dichloroethane/water system. The standard ionic
      partition coefficient values so obtained (log Pdce(o,C)) were correlated with log
      Poct values calculated by the CLOGP algorithm for the respective neutral
      molecules. RESULTS: The standard (i.e., intrinsic) lipophilicity values are shown
      to depend on a, the structure of the ion (nature, volume, charge), and b, on the
      Galvani potential difference at the ITIES (interface between two immiscible
      electrolyte solutions). CONCLUSIONS: The standard lipophilicity values were not
      influenced by counter-ions. In contrast, simulations showed that the increased
      apparent lipophilicity of cations, as measured by the shake-flask method in the
      presence of lipophilic anions, is fully accounted for by the resulting increase
      in the Galvani potential difference.

PMID- 11465430
TI  - The preparation, characterization, and evaluation of cationic microparticles for
      DNA vaccine delivery.

PMID- 11465431
TI  - Effects of tacrolimus and cyclosporin A on peptide transporter PEPT1 in Caco-2
      cells.

PMID- 11465432
TI  - Bone loading pattern around implants in average and atrophic edentulous maxillae:
      a finite-element analysis.
AB  - INTRODUCTION: Oral implants placed in the maxilla, especially the posterior
      region, have a lower success rate than those placed in the mandible. Poor bone
      quantity and quality have been suggested as a reason for this differential
      success rate. OBJECTIVE: The purpose of this study was, therefore, to evaluate
      stress and strain distributions around loaded implants in the normal and atrophic
      maxilla by finite-element (FE) analyses. MATERIAL: FE models of a solitary
      implant were generated to determine stresses and strains in the bone adjacent to
      the implant surface under loading conditions. STUDY DESIGN: Different bony
      situations and implant lengths were used in a FE model. Static loads were applied
      axially and the resulting stresses and strains calculated. RESULTS: Bone quality
      and quantity play a major role in decreasing bone strains adjacent to the implant
      surface under loading. It was found that stresses were more homogeneously
      distributed when more spongy bone was present. Decreased bone height was found to
      have less pronounced effects on strain and stress alterations than poor bone
      quality. Atrophic bony dimensions in combination with poor bone quality were
      associated with surface strains exceeding physiological levels (> 6,000
      microstrains). CONCLUSION: Our investigation indicates that supraphysiological
      bone strains adjacent to the implant surface should be expected under mechanical
      loading in the atrophic maxilla.

PMID- 11465433
TI  - Malformation of the vomer in submucous cleft palate.
AB  - BACKGROUND: Several criteria are described in the literature to diagnose a
      submucous cleft palate. Commonly the differences in the extent of the submucous
      cleft will not be as overt as in open clefts. Nevertheless, complete submucous
      cleft palate may cause imperfect palato-pharyngeal closure so that the affected
      person needs to undergo speech training and surgical treatment. PATIENTS: We
      investigated 30 patients who underwent palatal repair to correct this disorder.
      They were evaluated according to the Koch's documentation system. RESULTS: In all
      patients an additional malformation of the inner nose was found: The vomer was
      not fused with the palatal shelves. There were different degrees of severity of
      this vomerine malformation and they were not necessarily correlated with the
      extent of the palatal cleft. CONCLUSION: In our opinion, this malformation of the
      vomer should be seen as a typical symptom of classical submucous cleft palate.
      Discussion is needed on how the vomerine malformation should be incorporated into
      the surgical procedure. Since we know from septal surgery that a basal septal
      perforation will lead to disturbances of nasal breathing.

PMID- 11465434
TI  - Purulent pansinusitis, orbital cellulitis and rhinogenic intracranial
      complications.
AB  - OBJECTIVES: Acute pansinusitis is rarely seen in the maxillofacial surgery field,
      but often occurs in combination with orbital and intracranial involvement.
      Clinically this entity is of great importance, since it represents a severe
      disease with possibly disastrous consequences. PATIENTS: Aetiology, diagnosis and
      therapy of acute pansinusitis and its complications were analysed in 36 patients
      treated surgically from 1987 to 1996. RESULTS: Eighteen patients were aged
      between 3 and 21-years-old. Only eight suffered from pure pansinusitis, and three
      of an isolated purulent orbital infection. Of these 25 patients 20 had (pan
      )sinusitis with orbital, three with intracranial, and two with both orbital and
      intracranial complications. Intracranial involvement included meningitis, empyema
      and brain abscess. Aetiology was rhinogenic in 26, odontogenic in six patients,
      and traumatic in two cases. Radiological work-up included conventional
      radiographs and CT in most cases, MRI was only used with special indications.
      Microbiological examination detected single or multiple species of micro
      organisms with equal frequency. If multiple species were found, infection was
      mostly aerobic/anaerobic in combination. CONCLUSION: These purulent processes,
      frequently seen in young patients, require immediate surgical intervention and
      drainage with elimination of the cause of the disease if possible. Cooperation
      with other specialities is essential depending on the spread of the disease. In
      spite of the threatening acute symptoms, severe courses of disease or permanent
      defects should be avoidable.

PMID- 11465435
TI  - Autologous blood transfusion in oral and maxillofacial surgery patients with the
      use of erythropoietin.
AB  - BACKGROUND: Autologous blood transfusion presents few infectious or immunologic
      side effects. The aim of the present study was to determine the impact of
      autologous blood transfusion with or without recombinant human erythropoietin
      (rHuEPO) in patients who underwent elective maxillofacial operations. MATERIAL:
      Seventy eight consecutive patients (29 men and 49 women) underwent elective
      maxillofacial operations during the years 1990-95. STUDY DESIGN AND METHODS: The
      patients were randomly assigned to three groups: In group 1, 30 patients
      preoperatively underwent autologous blood predonation with intravenous injection
      of erythropoietin 600 lU/kg after each blood predonation and autologous blood
      transfusion intraoperatively; in group 2, 28 patients underwent the same
      procedure without erythropoietin and in group 3, 20 patients underwent homologous
      transfusion serving as control group. All patients received ferrous sulphate
      daily by mouth, preoperatively until one week postoperatively. RESULTS: Group 1
      patients showed higher levels of haematocrit, haemoglobin and red blood cell
      count pre- and postoperatively than the group 2 patients. It was also shown that
      the use of rHuEPO contributed to an improvement of the blood parameters of the
      patients in the group 1 compared with those of the patients in groups 2 and 3.

PMID- 11465436
TI  - Analysis of the osseous/metal interface of drill free screws and self-tapping
      screws.
AB  - AIM: A comparison of metal/osseous interface and bone remodelling after insertion
      of different types of titanium bone screws in vivo. MATERIAL: Samples of five of
      each of the following bone screw types were inserted into the anterior wall of
      the frontal sinus of five Gottingen minipigs: self-tapping micro- (1.5mm) and
      miniscrews (2.0 mm) or drill free micro- (1.5 mm) and miniscrews (2.0 mm) (Martin
      Medizintechnik, Tuttlingen, Germany). Screw length was 7mm. METHODS: Sequential
      intraperitoneal injections of fluorochromes were performed between the second and
      ninth postoperative week. After 6 months the pigs were sacrificed, the screw-bone
      blocks resected, and microradiographic, histological and fluorescence
      microscopical examinations were carried out. RESULTS: Using drill free screws,
      mean screw/bone contact was 88.4% (miniscrews), or 93.8% (microscrews). With self
      tapping miniscrews it was 54.9%, but in microscrews 81%; the differences were
      statistically significant (t-test: p<0.05). By fluorescence microscopy, the
      amount of bone remodelling (ratio of residual vs. newly formed bone) was
      measured. Significantly more of the residual bone was found in the region of the
      screw threads using drill free screws (miniscrews: mean 71.8%, microscrews: mean
      67.9%) than in the region of screw threads with self-tapping screws (miniscrews:
      mean 33.1%, microscrews: mean 42.4%). CONCLUSION: The present data support the
      view that screw/bone contact with drill free screws was superior to that of self
      tapping screws; the greater amount of original bone in the threads of drill free
      screws demonstrated that the insertion of drill free screws did not cause harm to
      the surrounding bone. Both results are important for osteosynthesis in regions
      where thin cortical bone is present, such as the central midface.

PMID- 11465437
TI  - Long-term results following reconstruction of craniofacial defects with titanium
      micro-mesh systems.
AB  - INTRODUCTION: Reconstruction of craniofacial defects can be carried out with
      autogenous tissue (calvarium, rib, iliac crest), allogeneic implants (AAA-bone,
      lyophilized cartilage) or alloplastic material (methacrylate, hydroxyapatite,
      titanium implants and mesh systems). Selection of the implant material used for
      reconstruction is still controversial. MATERIAL AND METHODS: At the Department of
      Oral and Maxillofacial Surgery, Kantonsspital Luzern, 20 patients with defects in
      the craniofacial and/or orbito-ethmoidal region have been treated using titanium
      micro-mesh between 1991 and 1998. Two different mesh systems, micro-titanium
      augmentation mesh and dynamic mesh, have been used for bony reconstruction in non
      load-bearing areas. The defects were caused by acute trauma, osteomyelitis of the
      frontal bone and previous operations. The titanium micro-mesh was used with the
      following indications: (1) immediate reconstruction in the primary treatment of
      comminuted fractures with bone loss in non load-bearing areas, (2) treatment of
      contour irregularities (possibly in combination with bone or cartilage grafts).
      All patients were followed up clinically and radiographically at quarterly
      intervals for a year. RESULTS: No wound infections, exposures or loss of the mesh
      have been observed. Long-term stability of the reconstructions was excellent.
      When walls of the paranasal sinuses were reconstructed complete repneumatisation
      took place. CONCLUSIONS: Advantages of this reconstructive technique are: (1)
      universal applicability (craniofacial, orbital, sinus defects, comminuted
      fractures); (2) stable 3-D reconstruction of complex anatomic structures were
      easily performed; (3) immediate availability with no donor site morbidity as bone
      or cartilage grafts were not necessary; (4) combination with bone or cartilage
      grafts is possible; and (5) very low susceptibility to infection.

PMID- 11465438
TI  - Effectiveness of a new perforated 0.15 mm poly-p-dioxanon-foil versus titanium
      dynamic mesh in reconstruction of the orbital floor.
AB  - INTRODUCTION: In recent years a new perforated PDS (poly-p-dioxanon) foil (0.15
      mm) has become available and has not yet been proven to be successful in
      reconstruction of the orbital floor after blow-out-fractures in randomized
      studies. The main aim of this clinical trial is to compare this new PDS foil with
      titanium dynamic mesh (0.3 mm) (TD), which is well established in reconstruction
      of the orbital floor. PATIENTS AND METHODS: In a prospective multicentre
      randomized trial, conducted between 1997 and 1998, out of 42 patients with
      fractures of the orbital floor, 28 patients needing material for reconstruction
      were randomized to receive either PDS foil or TD. In a comprehensive preoperative
      and postoperative protocol patients were monitored by the surgeon, radiologist
      and ophthalmologist with a postoperative follow-up of least 6 months. RESULTS:
      Maximum defects of the orbital floor were comparable in both groups (PDS group:
      13.3 mm, TD group: 13.9 mm). In both groups the surgical procedure was well
      tolerated, and functional and cosmetic results were evaluated as satisfactory by
      all patients. Ophthalmological evaluation, performed up to 6 months
      postoperatively, revealed double vision or vertical strabismus in nine patients
      (five PDS group, four titanium group). This was not confirmed subjectively in
      each single patient. Also ex- or enophthalmos, registered in seven patients of
      the PDS and four of the TD group (mainly + /- 1 mm) were not considered as
      relevant by the patients. CONCLUSION: The new 0.15 mm perforated PDS foil was
      comparable to 0.3 mm titanium mesh concerning functional and cosmetic outcome.
      Obviously, persisting ophthalmometric disorders were compensated very well in
      both groups. PDS foil is felt to be the preferred material since it is
      bioresorbable and more convenient to handle.

PMID- 11465439
TI  - Pumping injection of sodium hyaluronate for patients with non-reducing disc
      displacement of the temporomandibular joint: two year follow-up.
AB  - OBJECTIVES: The purpose of the present study was to examine the long-term effect
      of pumping injection of sodium hyaluronate into the TMJ in patients with non
      reducing disc displacement. PATIENTS: Sixty patients with non-reducing disc
      displacement underwent pumping injection of sodium hyaluronate (pumping group).
      Seventy-six patients with non-reducing disc displacements were observed without
      any active treatment (observation group). STUDY DESIGN: In both patient groups
      clinical signs and symptoms were observed periodically for 2 years. Variables
      such as age, range of maximum mouth opening, angle of posterior slope of the
      articular eminence and degenerative bony changes of the condyle at the initial
      visit were also examined. Cox hazards analysis was applied to examine the
      clinical outcome for such variables in addition to the results of pumping
      injection of sodium hyaluronate. RESULTS: Pumping injection of sodium hyaluronate
      seemed to have a favourable effect when compared with the control group
      (untreated) (p = 0.0002). However, the four background variables mentioned could
      not be explained as predictors of outcome. CONCLUSION: Pumping injection of
      sodium hyaluronate seems to be effective for non-reducing disc displacement of
      the temporomandibular joint.

PMID- 11465440
TI  - The fate of developing teeth in mandibular lengthening by distraction: an
      experimental study.
AB  - PURPOSE: The purpose of this study was to observe developing teeth in a
      lengthened mandible after distraction. MATERIAL: Ten mongrel dogs with deciduous
      dentitions were used. METHODS: A corticotomy was carefully made around a tooth
      bud and the external distractor (Orthofix M-100) was connected. After a 5-day
      latent period, distraction was started at a rate of 0.75 mm per day for 10
      consecutive days. Then, the lower jaw was stabilized by an external fixation to
      allow ossification. While the operation was performed on the left side
      (Distraction group), the contralateral side was studied for comparison (Control).
      In addition, a corticotomy, artificial fracture and external fixation were
      carried out to confirm the influence of the operation (Fracture group). Then
      macroscopic, radiographic and histological evaluations were carried out. RESULTS:
      In the Distraction group, the space between the wall of the dental follicle and
      the crown expanded as distraction began. The end of the calcified root became
      wider and irregular during the distraction period, and finally, the apex closed.
      In the Fracture group, the teeth erupted although slight alterations of the root
      shape were observed in association with the operation period. CONCLUSION: The
      root became irregular, but the teeth erupted within the distraction area.

PMID- 11465441
TI  - Nanocrystalline metal oxides as unique chemical reagents/sorbents.
AB  - A new family of porous inorganic solids based on nanocrystalline metal oxides is
      discussed. These materials, made up of 4-7 nm MgO, CaO, Al2O3, ZnO, and others,
      exhibit unparalleled destructive adsorption properties for acid gases, polar
      organics, and even chemical/biological warfare agents. These unique sorption
      properties are due to nanocrystal shape, polar surfaces, and high surface areas.
      Free-flowing powders or consolidated pellets are effective, and pore structure
      can be controlled by consolidation pressures. Chemical properties can be adjusted
      by choice of metal oxide as well as by incorporating other oxides as monolayer
      films.

PMID- 11465442
TI  - Halogen bonding: a paradigm in supramolecular chemistry.
AB  - The term halogen bonding describes the tendency of halogen atoms to interact with
      lone pair possessing atoms. The binding features and structural properties of
      halogen bonding are discussed and applied to drive the intermolecular self
      assembly of hydrocarbons and perfluorocarbons in chemo-, site-, and
      enantioselective supramolecular synthesis. The halogen bonding is thus an
      effective and reliable tool in crystal engineering at the disposal of the
      supramolecular chemist.

PMID- 11465443
TI  - Thermodynamics of catalytic formation of dimethyl ether from methanol in acidic
      zeolites.
AB  - We present a theoretical study of the formation of the first intermediate,
      dimethyl ether, in the methanol to gasoline conversion within the framework of an
      ab initio molecular dynamics approach. The study is performed under conditions
      that closely resemble the reaction conditions in the zeolite catalyst including
      the full topology of the framework. The use of the method of thermodynamic
      integration allows us to extract the free-energy profile along the reaction
      coordinate. We find that the entropic contribution qualitatively alters the free
      energy profile relative to the total energy profile. Different transition states
      are found from the internal and free energy profiles. The entropy contribution
      varies significantly along the reaction coordinate and is responsible for
      stabilizing the products and for lowering the energy barrier. The hugely
      inhomogeneous variation of the entropy can be understood in terms of elementary
      processes that take place during the chemical reaction. Our simulations provide
      new insights into the complex nature of this chemical reaction.

PMID- 11465444
TI  - Cooperative multipoint recognition of organic dyes by bis(beta-cyclodextrin)s
      with 2,2'-bipyridine-4,4'-dicarboxy tethers.
AB  - A series of novel 6,6'-bis(beta-cyclodextrin)s linked by 2,2'-bipyridine-4,4'
      dicarboxy tethers; that is, 2,2'-bipyridine-4,4'-dicarboxy-bridged bis(6-O-beta
      cyclodextrin) (2) and N,N'-bis(2-aminoethyl )-2,2'-bipyridine-4,4'-dicarboxamide
      bridged (3), N,N'-bis(5-amino-3-azapentyl)-2,2'-bipyridine-4,4'-dicarboxamide
      bridged (4) and N,N'-bis(8-amino-3,6-diazaoctyl)-2,2'-bipyridine-4,4'
      dicarboxamide-bridged bis(6-amino-6-deoxy-beta-cyclodextrin) (5), has been
      synthesized as cooperative multipoint-recognition receptor models. The inclusion
      complexation behavior of 2-5 with organic dyes; that is, ammonium 8-anilino-1
      naphthalenesulfonate, Brilliant Green, Methyl Orange, Acridine Red, and Rhodamine
      B, has been investigated in aqueous phosphate buffer solutions (pH 7.20) at 25
      degrees C by means of ultraviolet, fluorescence, and circular dichroism
      spectrometry as well as by fluorescence lifetime measurements. The spectral
      titrations gave the complex stability constants (Ks) and Gibbs' free energy
      changes (deltaG degrees) for the inclusion complexation of 2-5 with the organic
      dyes and other thermodynamic parameters (deltaH degrees and deltaS degrees) for
      the inclusion complexation of 2-4 with the fluorescent dyes Acridine Red and
      Rhodamine B. Bis(beta-cyclodextrin)s 2-5 displayed higher binding abilities
      toward most of the examined dye molecules than native beta-cyclodextrin 1; this
      is discussed from the viewpoints of the size/shape-fit concept, the induced-fit
      interaction, and cooperative, multipoint recognition by the bridging chain and
      the dual hydrophobic cavities. Thermodynamically, the inclusion complexation of 2
      4 with Acridine Red is totally enthalpy driven with a negative or minor positive
      entropic contribution, but the inclusion complexation with Rhodamine B is mainly
      entropy-driven with a mostly positive, but occasionally negative, enthalpic
      contribution; in some cases this determines the complex stability.

PMID- 11465445
TI  - A structural and theoretical analysis of transition metalloporphodimethenes and
      their relationship with metalloporphyrins.
AB  - The paper reports the synthesis of the first-row transition metal
      hexaethylporphodimethene derivatives [(Et6N4)M] [M=Mn, 3; M=Co, 5; M = Cu, 7] on
      a multigram scale, which makes them easily available for reactivity studies.
      After synthesis they were converted into the corresponding five-coordinate
      [(Et6,N4)M(L)] [M = Mn, L =THF, 8; M =Co, L = Py, 9] and six-coordinate
      [(Et6,N4)M(L)2] [M = Mn, L = THF, 10; M = Mn, L = Py, 11] derivatives. The
      compounds mentioned above and those recently reported, namely the iron and nickel
      derivatives 4, 6, 12, and 13, permit the presentation of the first coherent
      report on the structural, optical, magnetic, and electronic characteristics of
      the first-row transition metal porphodimethene derivatives. The experimental
      results, coupled with a detailed theoretical analysis (Density Functional Theory,
      DFT), give the appropriate background for future development of the
      porphodimethene skeleton, which paves the way from porphyrinogen to porphyrins.
      In addition, this report, encompassing the entire first row of transition metal
      ion porphodimethenes, allows a valuable comparison to be made with the
      corresponding metallated porphyrins, thus establishing the peculiar differences
      in terms of structural and electronic properties and potential reactivity.

PMID- 11465446
TI  - Kinetic and spectroscopic study of 1O2 generation from H2O2 catalyzed by LDH
      MoO4(2-) (LDH=layered double hydroxide).
AB  - Layered double hydroxides (LDHs), exchanged with molybdate, decompose H2O2 to
      form one molecule of singlet-state dioxygen (1O2) from two molecules of H2O2. The
      dependence of the kinetics of H2O2 decomposition on Mo and H2O2 concentrations
      and on temperature has been related to structural characteristics of the material
      (X-ray diffraction (XRD), scanning electron microscopy (SEM), IR spectroscopy, N2
      adsorption, thermogravimetry) and to molybdate speciation as revealed by in-situ
      studies in the presence of peroxide (FT Raman, diffuse reflectance UV/visible
      spectroscopy). The H2O2 decomposition rate is linearly correlated with the amount
      of LDH-exchanged molybdate, except when a considerable fraction of the molybdate
      occupies less accessible interlayer positions. A maximum in the H2O2
      decomposition rate as the H2O2 concentration is increased is due to the
      successive formation of mono-, di-, tri-, and tetraperoxomolybdates. This
      behavior was modeled successfully by using the equilibrium constants for
      formation of the Mo-peroxo complexes, and the rate constants for decay of the
      peroxomolybdates with 1O2 liberation. Time-resolved diffuse reflectance and Raman
      observations of the various MoO4(2-)-peroxide adducts are in line with the
      proposed kinetic scheme. Of all the Mo-peroxo species on the LDH, the
      triperoxomolybdate has the highest rate for decay to 1O2. Comparison with the
      kinetics of dissolved molybdate shows that the monomolecular decay of all
      peroxomolybdate species proceeds much faster at the LDH surface than in solution.
      Consequently, maximal rates per Mo atom are at least twice as high for the
      heterogeneous LDH catalyst as for the homogeneous systems.

PMID- 11465447
TI  - Self-assembly of frameworks with specific topologies: construction and anion
      exchange properties of M3L2 architectures by tripodal ligands and silver(I)
      salts.
AB  - Three five-component architectures, compounds 3, 4, and 5 were obtained by self
      assembly of tripodal 1,3,5-tris(imidazol-1-ylmethyl )-2,4,6-trimethylbenzene (6)
      and 1,3,5-tris(benzimidazol-2-ylmethyl)benzene (7) ligands with silver(I) salts.
      The structures of these novel complexes have been determined by X-ray
      crystallography. The results of structural analysis indicate that these
      frameworks have same M3L2 components, but different structures. Compounds 3 and 4
      are both M3L2 type cage-like complexes, while the 5 is an open trinuclear
      complex. The complex 3 is a cylindrical cage with simultaneous inclusion of a
      perchlorate anion inside of the cage as a guest molecule. Such guests can be
      exchanged for other anions through the open edge of the cage as evidenced by
      crystal structure of 4. The results demonstrate that the molecular M3L2 type cage
      can act as a host for anions and provide a nice example of supramolecular
      architectures with interesting properties and possible applications.

PMID- 11465448
TI  - C3-chiral tripodal amido complexes.
AB  - A comprehensive study into the coordination chemistry of two C3-chiral tripodal
      amido ligands has been carried out. The amido ligands contain a trisilylmethane
      backbone and chiral peripheral substituents. The amine precursors. HC(SiMe2NH[(S)
      1-phenylethyl]]3 (1) and HC[SiMe2NH[(R)-1-indanyl]]3 (2) were found to be in
      equilibrium in solution with the cyclic diamines HC[SiMe2N[(S)-1
      phenylethyl]2](SiMe2NH-[(S)-1-phenylethyl]] (3) and HC[SiMe2NH[(R)-1
      indanyl]][SiMe2NH[(R)-1-indanyl]) (4), which are generated upon ejection of one
      molecule of the chiral primary amine. Reaction of these equilibrium mixtures with
      three molar equivalents of butyllithium instantaneously gave the trilithium
      triamides HC[SiMe2N(Li)[(S)-1-phenylethyl]]3 (5) and HC[SiMe2N(Li)[(R)-1
      indanyl]]3 (6), both of which were characterised by an X-ray diffraction study.
      Both lithium compounds possess a central heteroadamantane core, in which the two
      coordinate Li atoms are additionally weakly solvated by the three aryl groups of
      the chiral peripheral substituents, the Li-C contacts being in the range of 2.65
      2.73 A. Reaction of 5 and 6 with [TiCl4(thf)2] and ZrCl4 gave the corresponding
      amido complexes [TiCl-[HC[SiMe2N[(S)-1-phenylethyl]]3]] (7), [TiCl(HC[SiMe2N[(R)
      1-indanyl]]3]] (8), [ZrCl[HC[SiMe2N[(S)-1-phenylethyl]]3]] (9) and
      [ZrCl[HC[SiMe2N[(R)-1-indanyl]]3]] (10), respectively. Of these, compound 7 was
      structurally characterised by X-ray structure analysis and was shown to possess a
      C3-symmetrical arrangement of the tripod ligand. The chiral anionic dinuclear
      complex [Li-(OEt2)4][Zr2Cl3[HC[SiMe2N[(S)-1-phenylethyl]]3]2] (11) was isolated
      from reaction mixtures leading to 9. An X-ray diffraction study established its
      dimeric structure, in which the chiral amido ligands cap the two metal centres,
      which are linked through three symmetrically arranged, bridging chloro ligands.
      Reaction of 9 and 10 with a series of alkyl Grignard and alkyllithium reagents
      yielded the corresponding alkylzirconium complexes. X-ray structure analyses of
      [Zr(CH3)[HC[SiMe2N[(S)-1-phenylethyl]]3]] (12) and [Zr(CH3)-[HC[SiMe2N)[(R)-1
      indanyl]]3]] (20) established their detailed molecular arrangements. While the
      reaction of 12 with the aryl ketones PhC(O)R (R = CH = CHPh, iPr, Et) gave the
      corresponding C-O insertion products, which contain an additional chiral centre
      in the alkoxy group, with low stereoselectivity (0-40% de). The corresponding
      conversions with several aryl aldehydes yielded the alkoxo complexes with high
      stereoselectivity. Upon hydrolysis, the chiral alcohols were isolated and shown
      to have enantiomeric excesses between 68 and 82%. High stereodiscrimination was
      also observed in the insertion reactions of several chiral ketones and aldehydes.
      However, this was shown to originate primarily from the chirality of the
      substrate. In analogous experiments with carbonyl compounds, the ethyl- and butyl
      zirconium analogues of 12 did not undergo CO insertion into the metal-alkyl bond.
      Instead, beta-elimination and formal insertion into the metal-hydride bond
      occurred. It was found that the elimination of the alkene was induced by

PMID- 11465449
TI  - Intramolecular iron(II)-catalyzed nitrogen transfer reactions of unsaturated
      alkoxycarbonyl azides: a facile and stereoselective route to 4,5-disubstituted
      oxazolidinones.
AB  - Intramolecular FeII-catalyzed reactions of various unsaturated alkoxycarbonyl
      azides are described. The reactions occur in the presence of stoichiometric
      amounts of trimethyl silyl chloride employing ethanol as the solvent. The
      corresponding 2-alkenyloxycarbonyl azides 5, 9, 18, 20, 22, and 24 gave the
      products 7/8, 10/11, 19, 21, 23, and 25 of an olefin chloroamination in moderate
      to good yields (47-72%). The facial diastereoselectivity of the ring closing C-N
      bond forming step is good both in cyclic (20, 24) and in acyclic substrates (5,
      18, 22) (>90% ds). The subsequent chlorine atom transfer occurs selectively in
      cyclic systems (20, 24) and in systems (9b, 18) which exhibit a conformational
      bias in the postulated radical intermediate 14. The lifetime tau of this elusive
      intermediate was estimated from the loss of stereochemical information in
      conformationally unrestricted systems (9a, 22) and from the data obtained with a
      radical clock (31-->32). 2-Alkynyloxycarbonyl azides 34 and 36 also yield
      chloroamination products which are obtained exclusively as the (Z)-isomers 35 and
      37 (81-99% yield). The products of the tert-butyl-substituted substrates 38
      undergo an immediate rearrangement/solvolysis reaction in the reaction mixture
      and gave the 5-alkoxyoxazolidinones 39 (93-99% yield).

PMID- 11465450
TI  - A mixed fullerene-ferrocene thermotropic liquid crystal: synthesis, liquid
      crystalline properties, supramolecular organization and photoinduced electron
      transfer.
AB  - Grafting of a ferrocene-containing liquid-crystalline malonate derivative to C60
      led to the mixed fullerene-ferrocene material 1 which gave rise to a smectic A
      phase. Cholesterol was used as liquid-crystalline promoter. X-ray diffraction
      experiments and volumetric measurements indicated that 1 is organized in double
      layered structures. The corresponding supramolecular organization within the
      mesomorphic lamellar phase is characterized by a microsegregation of the
      different units (ferrocene, fullerene, and cholesterol) in distinct sublayers. In
      such a smectic A phase, C60 imposes the arrangement of the other molecular
      moieties. Photophysical studies revealed that electron transfer occurs from the
      donor ferrocene to the electron accepting fullerene. The formation of a long
      lived radical pair, with lifetimes of the order of several hundred nanoseconds,
      was confirmed by time-resolved spectrometry, especially in the near infrared
      region, in which the radical anion of the fullerene moiety displays its
      characteristic fingerprint absorption.

PMID- 11465451
TI  - New molecular complexes of fullerenes C60 and C70 with tetraphenylporphyrins
      [M(tpp)], in which M=H2, Mn, Co, Cu, Zn, and FeCl.
AB  - New molecular complexes of fullerenes C60 and C70 with tetraphenylporphyrins
      [M(tpp)] in which M-H2, MnII, CoII, CuII, ZnII and Fe(III)Cl, have been
      synthesised. Crystal structures of two C60 complexes with H2TPP, which differ
      only in the number of benzene solvated molecules, and C60 and C70 complexes with
      [Cu(tpp)] have been studied. The fullerene molecules form a honeycomb motif in
      H2TPP.2C60. 3C6H6, puckered graphite-like layers in H2TPP.2C60.4C6H6, zigzag
      chains in [Cu(tpp)].C70.1.5C7H8.0.5C2HCl3 and columns in [Cu(tpp)]2.C60. H2TPP
      has van der Waals contacts with C60 through nitrogen atoms and phenyl groups.
      Copper atoms of the [Cu(tpp)] molecules are weakly coordinated with C70, but form
      no shortened contacts with C60. The formation of molecular complexes with
      fullerenes affects the ESR spectra of [M(tpp)] (M = Mn, Co and Cu). [Mn(tpp)] in
      the complex with C70 lowers its spin state from S = 5/2 to S = 1/2, whereas
      [Co(tpp)] and [Cu(tpp)] change the constants of hyperfine interaction. ESR, IR,
      UV-visible and X-ray photoelectron spectroscopic data show no noticeable charge
      transfer from the porphyrinate to the fullerene molecules.

PMID- 11465452
TI  - Synthesis of radialene-shaped pyrroles by multiple-anion-capture reactions of 1,3
      dianions.
AB  - A new multicomponent reaction (multiple-anion-capture reaction) of 1,3-dianions
      with nitriles and oxalic acid-bis(imidoyl)chlorides is reported. This process
      allows for an efficient and regioselective synthesis of a variety of radialene
      shaped pyrroles which constitute structurally new and interesting heterocyclic
      systems. The cyclization products can be considered as aza-analogues of the
      pharmacologically relevant substance class of 3-acetyltetramic acids. A
      rationalization of the experimental results is given based on quantum chemical
      computations.

PMID- 11465453
TI  - Discovery of a new efficient chiral ligand for copper-catalyzed enantioselective
      Michael additions by high-throughput screening of a parallel library.
AB  - A combinatorial library of 125 chiral Schiff base ligands 5 was synthesized with
      the use of solution-phase parallel synthesis and solid-phase extraction (SPE)
      techniques to scavenge excess reagents and reaction by-products and avoid
      chromatography. The synthetic methodology coupled five N-Boc-protected beta-amino
      sulfonyl chlorides 1a-e with five different amines 2f-j to give 25 N-Boc
      sulfonamides 3, which were in turn deprotected and coupled with five
      salicylaldehydes 4p-t to give 125 ligands 5 in good yields and of sufficient
      purity to be used in ligand-catalyzed reactions. These ligands were tested in the
      copper-catalyzed conjugate addition of dialkyl zinc to cyclic and acyclic enones.
      A multisubstrate high-throughput screening of the library was performed with an
      equimolar mixture of 2-cyclohexenone and 2-cycloheptenone (9 and 10,
      respectively, 0.2 mmol total), with 5.5 mol% ligand 5 (0.011 mmol) and 5 mol%
      Cu(OTf)2 (OTf= OSO2CF3) (0.010 mmol) in 1:1 toluene/ hexane at - 20 degrees C.
      From the screening of the library, 5bhr was identified as the best ligand, which
      yielded 3-ethylcyclohexanone (12) and 3-ethylcycloheptanone (13) in 82% and 81%
      ee, respectively, and complete conversions. Under optimized conditions (2.75 mol%
      5bhr, 2.5 mol% copper(i) triflate, toluene as reaction solvent), improved results
      were obtained for 12 (90% ee, 93% yield) and for 13 (91% ee, 95% yield). Selected
      ligands 5 were also tested in the addition of Me2Zn to 2-cyclohexenone (9, ee up
      to 79%), of Et2Zn to 2-cyclopentenone (11, ee up to 80%) and to acyclic enones 16
      and 17 (ee up to 50%).

PMID- 11465454
TI  - Activation of C--H... Halogen (Cl, Br, and I) hydrogen bonds at the
      organic/inorganic interface in fluorinated tetrathiafulvalenes salts.
AB  - The electrocrystallization of fluorinated bis(2,2'
      difluoropropylenedithio)tetrathiafulvalene (1) in the presence of linear (ICl2-,
      IBr2-, I2Br-) or cluster ([Mo6Cl14]2-) anions affords 1:1 and 2:1 cation radical
      salts such as [1][ICl2] and [1]2[Mo6Cl14].(CH3CN)2. In both salts, the 1*+
      radical ion adopts a boat conformation and envelops the anion through C
      H...Hal(anion) (Hal(anion) = Cl, Br, I) hydrogen bonds. This demonstrates the
      activating role of the neighboring electron-withdrawing CF2 moieties in the
      stabilization of bi- or trimolecular neutral entities. With smaller linear
      anions, fluorine segregation controls the solid-state associations of the
      bimolecular [1]*+[X] entities, and gives rise to layered materials with a limited
      overlap interaction between the open-shell organic cations and magnetic spin
      chain behavior. With the larger [Mo6Cl14]2 ions, a strong overlap interaction
      between radical cations gives rise to diamagnetic [1]2(2+) dimers, which
      alternate with the cluster anions to form hybrid organic/inorganic
      ...[1]2(2+)[Mo6Cl14]2... chains. This behavior is also observed in
      [2]2(2+)[Mo6Cl14]2-.(CH2Cl2)2, in which compound 2 is the unsymmetrically
      substituted (ethylenedithio)(2,2'-difluoropropylenedithio)tetrathiafulvalene. On
      the other hand, the unsymmetrically substituted 2,2'
      difluoropropylenedithiotetrathiafulvalene (3) affords a mixed-valence 4:1 salt
      with [Mo6Cl14]2, which is formulated as [3]4[Mo6Cl14].(CH3CN)2. This
      semiconducting salt is characterized by the coexistence of both the
      fluorine/fluorine segregation (with solvent inclusion) and the organic/inorganic
      segregation (with delocalized overlap interactions). Both Csp2-H...Cl and Csp3
      H...Cl hydrogen bonds facilitate the stabilization of the organic/inorganic
      interface and the presence of conducting organic slabs.

PMID- 11465455
TI  - Ring-opening polymerisation of silver-diphosphine [M2L3] coordination cages to
      give [M2L3]infinity coordination polymers.
AB  - [M2L3] coordination cages and linear [M2L3]infinity polymers of the rigid,
      bridging diphosphines bis(diphenylphosphino)acetylene (dppa) and trans-1,2
      bis(diphenylphosphino)ethylene (dppet) with silver(I) salts have been
      investigated in the solution and solid states. Unlike flexible diphosphines, 1:1
      dppa/AgX mixtures do not selectively form discrete [Ag2(diphos)2(X)2]
      macrocycles; instead dynamic mixtures of one-, two- and three-coordinate
      complexes are formed. However, 3:2 dppa/AgX ratios (X = SbF6. BF4, O3SCF3 or NO3)
      do lead selectively to new [M2L3] triply bridged cage complexes [Ag2(dppa)3(X)2]
      1a-d (X = SbF6 a, BF4 b, O3SCF3 c, NO3 d), which do not exhibit Ag-P bond
      dissociation at room temperature on the NMR time scale (121 MHz). Complexes la-d
      were characterised by X-ray crystallography and were found to have small internal
      cavities, helical conformations and multiple intramolecular aromatic
      interactions. The nucleophilicity of the anion subtly influences the cage shape:
      Increasing nucleophilicity from SbF6 (1a) through BF4 (1b) and O3SCF3 (1c) to NO3
      (1d) increases the pyramidal distortion at the AgP3 centres, stretching the cage
      framework (with Ag...Ag distances increasing from 5.48 in 1a to 6.21 A in 1d) and
      giving thinner internal cavities. Crystal packing strongly affected the size of
      the helical twist angle, and no correlation between this parameter and the Ag-Ag
      distance was observed. When crystalline 1c was stored in its supernatant for 16
      weeks, conversion occured to the isostoichiometric [M2L3]infinity coordination
      polymer [Ag(dppa)2Ag(dppa)(O3SCF3)2]infinity (1c'). X-ray crystallography
      revealed a structure with ten-membered Ag2(dppa)2 rings linked into infinite one
      dimensional chains by a third dppa unit. The clear structural relationship
      between this polymer and the precursor cage 1c suggests a novel example of ring
      opening polymerisation. With dppet, evidence for discrete [M2L3] cages was also
      found in solution, although 31P NMR spectroscopy suggested some Ag-P bond
      dissociation. On crystallisation, only the corresponding ring-opened polymeric
      structures [M2L3]infinity could be obtained. This may be because the greater
      steric bulk of dppet versus dppa destabilises the cage and favours the ring
      opening polymerisation.

PMID- 11465456
TI  - Energy isosbestic points in third-row transition metal alloys.
AB  - The total electronic energies of the six electrons per atom (e per atom) alloys
      W, TaRe, HfOs, and YIr and the seven electrons per atom alloys Re, WOs, TaIr,
      HfPt, and YAu have been calculated in the local density approximation of density
      functional theory. When one considers common alloy structures such as atomically
      ordered variants of the body-centered cubic, face-centered cubic, or hexagonally
      closest packed structures and plots the total electronic energy as a function of
      the unit cell parameter, one finds for both the six and seven electrons per atom
      series energetic isosbestic points. An energetic isosbestic point corresponds to
      a critical value of the size parameter for which all members of the 6 or 7 e per
      atom series of compounds have nearly identical total electronic energy. Just as
      in spectroscopy, where the existence of such isosbestic points is the hallmark of
      two compounds present in the mixture, an energy isosbestic point implies there
      are just two separate energy curves. For both series it is found that the total
      electronic energy can be viewed as the weighted sum of a purely covalent term and
      a purely ionic term. Two semi-quantitative models are proposed to account for
      these two separate energies. In the first model the total energy is viewed as the
      sum of the elemental structural energy plus an ionic energy based on the Born
      Mayer ionic model. In the second model one considers within the confines of mu2
      Huckel theory the evolution of the total electronic energy as the Coulombic Hii
      integrals change in value.

PMID- 11465457
TI  - Total synthesis of agosterol A: an MDR-modulator from a marine sponge.
AB  - The first total synthesis of agosterol A, a modulator of multidrug resistance
      (MDR) mediated by P-gp and MRP1, and isolated from a marine sponge, was achieved
      from ergosterol by utilizing a regioselective epoxy-cleavage reaction and
      regioselective dehydroxylation as the key reactions.

PMID- 11465458
TI  - Mechanism of 1,6-addition reactions of organocuprates: detailed NMR spectroscopic
      study of a cuprate-enyne pi complex.
AB  - A detailed NMR-spectroscopic study of the multiply 13C-labeled cuprate pi
      complexes 2, 2a and 2b was carried out. The 13C,13C coupling constants observed
      were interpreted in terms of a deformation of the cuprate-alkene complex from the
      expected idealized square plane. This conclusion is in agreement with NOESY and
      ROESY data acquired with unlabeled material.

PMID- 11465459
TI  - Metal complexes of a biconcave porphyrin with D4-structure--versatile chiral
      shift agents.
AB  - Representative metal complexes of a biconcave D4-symmetric porphyrin were
      synthesised by metalion insertion into the porphyrin ligand 1. The NMR spectra
      suggested D4-symmetry for the ZnII and dioxo-RuVI complexes of 1 and C4-symmetry
      for the unsymmetrically ligated RuII and RhIII complexes. Metal complexes of 1
      proved to be versatile chiral 1H NMR shift agents for a broad spectrum of organic
      amines, alcohols, carboxylic acids, esters, nitriles and nonpolar fullerene
      derivatives. A practical analysis of chiral substrates with 1 covers enantiomeric
      excesses beyond 99%. An X-ray structure of (1:1)-cocrystals of an achiral,
      biconcave CoII porphyrinate and C60 provided the first detailed insights into the
      structure of such a biconcave metallo-porphyrinate. It also showed remarkable
      packing of the carbon sphere against the main concave units of the porphyrin and
      gave clues about the relevant interactions between biconcave porphyrins and
      fullerenes.

PMID- 11465460
TI  - Self-assembly and dynamics of [2]- and [3]rotaxanes with a dinuclear macrocycle
      containing reversible Os-N coordinate bonds.
AB  - With a dinuclear macrocycle 2 that contains weak reversible OsVI-N coordinate
      bonds, self-assembly and equilibrium dynamics of [2]- and [3]rotaxanes have been
      investigated. When the macrocycle 2 was mixed together with threads 4a-e, which
      all contain an adipamide station but different sizes of end groups,
      [2]pseudorotaxane- and rotaxane-like complexes were immediately formed with large
      association constants of >7 x 103M(-1) in CDCl3 at 298 K. Exchange dynamics,
      explored by 2D-EXSY experiments, suggest that assembly and disassembly of
      complexes occur through two distinct pathways, slipping or clipping, and this
      depends on the size of the end groups. The slipping pathway is predominant with
      smaller end groups that give pseudorotaxane-like complexes, while the clipping
      pathway is observed with larger end groups that yield rotaxane-like complexes.
      Under the same conditions, exchange barriers (deltaG++) were 14.3 kcalmol(-1) for
      4a and 16.7 kcalmol(-1) for 4d, and indicate that the slipping process is at
      least one order of magnitude faster than the clipping process. Using threads 13a
      and 13b that contain two adipamide groups, more complicated systems have been
      investigated in which [2]rotaxane, [3]rotaxane, and free components are in
      equilibrium. Concentration- and temperature-dependent 1H NMR spectroscopic
      studies allowed the identification of all possible elements and the determination
      of their relative distributions in solution. For example, the relative
      distribution of the free components, [2]rotaxane, and [3]rotaxane are 30, 45, and
      25 %, respectively, in a mixture of 2 (2mM) and 13a (2mM) in CDCl3 at 10 degrees
      C. However, [3]rotaxane exists nearly quantitatively in a mixture of 2 (4 mM) and
      13 a (2 mM) in CDCl3 at a low temperature - 10 degrees C.

PMID- 11465461
TI  - The effect of charged axial ligands on the EPR parameters in oxovanadium(IV)
      compounds: an unusual reduction of the Az (51V) values.
AB  - Two series of octahedral oxovanadium(IV) compounds, containing charged or neutral
      axial ligands, with the tetradentate amidate molecules Hcapca and H2capcah of the
      general formulae trans-[V(IV)OX(capca)]0/+ (where X = Cl- (1.CH2Cl2), SCN- (2),
      N3 (3), CH3COO- (4), PhCOO- (5), imidazole (6. CH3NO2), and eta-nBuNH2 (7)) and
      cis-[V(VI)OX(Hcapcah)]0/+ (where X = Cl- (8.0.5CH2Cl2), SCN (9), N3 (10.2CH3OH),
      and imidazole (11)), were synthesized and characterized by X-ray crystallography
      (1.CH3OH,8.CHCl3, 9.2CH3CN, 10.CH3CN and cis-[VO(imidazole)(Hcapcah)+) and
      continuous-wave electron paramagnetic resonance (cw EPR) spectroscopy. In
      addition to the synthesis, crystallographic and EPR studies, the optical,
      infrared and magnetic properties (room temperature) of these compounds are
      reported. Ab initio calculations were also carried out on compound 8 CHCl3 and
      revealed that this isomer is more stable than the trans isomer, in good agreement
      with the experimental data. The cw EPR studies of compounds 1-5, that is, the
      V(IV)O2+ species containing monoanionic axial ligands, revealed a novel
      phenomenon of the reduction of their A, components by about 10% relative to the
      N4 reference compounds ([V(IV)O-(imidazole)4]2+ and [V(IV)O(2,2-bipyridine)2]2+).
      In marked contrast, such a reduction is not observed in compounds 6. CH3NO2-11,
      which contain neutral axial ligands. Based on the spin-Hamiltonian formalism a
      theoretical explanation is put forward according to which the observed reduction
      of Az is due to a reduction of the electron - nuclear dipolar coupling (P). The
      present findings bear strong relevance to cw EPR studies of oxovanadium(IV) in
      vanadoproteins, V(IV)O2+-substituted proteins, and in V(IV)O2+ model compounds,
      since the hyperfine coupling constant, Az, has been extensively used as a
      benchmark for identification of equatorial-donor-atom sets in oxovanadium(IV)
      complexes.

PMID- 11465462
TI  - Automatic segmentation of subcortical brain structures in MR images using
      information fusion.
AB  - This paper reports a new automated method for the segmentation of internal
      cerebral structures using an information fusion technique. The information is
      provided both by images and expert knowledge, and consists in morphological,
      topological, and tissue constitution data. All this ambiguous, complementary and
      redundant information is managed using a three-step fusion scheme based on fuzzy
      logic. The information is first modeled into a common theoretical frame managing
      its imprecision and incertitude. The models are then fused and a decision is
      taken in order to reduce the imprecision and to increase the certainty in the
      location of the structures. The whole process is illustrated on the segmentation
      of thalamus, putamen, and head of the caudate nucleus from expert knowledge and
      magnetic resonance images, in a protocol involving 14 healthy volunteers. The
      quantitative validation is achieved by comparing computed, manually segmented
      structures and published data by means of indexes assessing the accuracy of
      volume estimation and spatial location. Results suggest a consistent volume
      estimation with respect to the expert quantification and published data, and a
      high spatial similarity of the segmented and computed structures. This method is
      generic and applicable to any structure that can be defined by expert knowledge
      and morphological images.

PMID- 11465463
TI  - An artificial intelligent algorithm for tumor detection in screening mammogram.
AB  - Cancerous tumor mass is one of the major types of breast cancer. When cancerous
      masses are embedded in and camouflaged by varying densities of parenchymal tissue
      structures, they are very difficult to be visually detected on mammograms. This
      paper presents an algorithm that combines several artificial intelligent
      techniques with the discrete wavelet transform (DWT) for detection of masses in
      mammograms. The AI techniques include fractal dimension analysis, multiresolution
      markov random field, dogs-and-rabbits algorithm, and others. The fractal
      dimension analysis serves as a preprocessor to determine the approximate
      locations of the regions suspicious for cancer in the mammogram. The dogs-and
      rabbits clustering algorithm is used to initiate the segmentation at the LL
      subband of a three-level DWT decomposition of the mammogram. A tree-type
      classification strategy is applied at the end to determine whether a given region
      is suspicious for cancer. We have verified the algorithm with 322 mammograms in
      the Mammographic Image Analysis Society Database. The verification results show
      that the proposed algorithm has a sensitivity of 97.3% and the number of false
      positive per image is 3.92.

PMID- 11465464
TI  - Consistent image registration.
AB  - This paper presents a new method for image registration based on jointly
      estimating the forward and reverse transformations between two images while
      constraining these transforms to be inverses of one another. This approach
      produces a consistent set of transformations that have less pairwise registration
      error, i.e., better correspondence, than traditional methods that estimate the
      forward and reverse transformations independently. The transformations are
      estimated iteratively and are restricted to preserve topology by constraining
      them to obey the laws of continuum mechanics. The transformations are
      parameterized by a Fourier series to diagonalize the covariance structure imposed
      by the continuum mechanics constraints and to provide a computationally efficient
      numerical implementation. Results using a linear elastic material constraint are
      presented using both magnetic resonance and X-ray computed tomography image data.
      The results show that the joint estimation of a consistent set of forward and
      reverse transformations constrained by linear-elasticity give better registration
      results than using either constraint alone or none at all.

PMID- 11465465
TI  - An algorithm using projection onto subspace of prior distributions for long
      wavelength sound wave CT.
AB  - The stationary long-wavelength sound wave computed tomography is a nonlinear
      inverse problem that requires the use of prior information of the object.
      However, the prior assumptions that are usually used in similar inverse problems
      are more or less inappropriate. In this paper, a new reconstruction algorithm
      using the prior information is proposed and compared with subspace regularization
      method and Marquardt reconstruction algorithms. The simulation shows that the
      proposed algorithm can give a better reconstructed result whether the actual
      distribution is compatible or incompatible with the prior distributions.

PMID- 11465466
TI  - Automated detection of pulmonary nodules in helical CT images based on an
      improved template-matching technique.
AB  - The purpose of this study is to develop a technique for computer-aided diagnosis
      (CAD) systems to detect lung nodules in helical X-ray pulmonary computed
      tomography CT) images. We propose a novel template-matching technique based on a
      genetic algorithm (GA) template matching (GATM) for detecting nodules existing
      within the lung area; the GA was used to determine the target position in the
      observed image efficiently and to select an adequate template image from several
      reference patterns for quick template matching. In addition, a conventional
      template matching was employed to detect nodules existing on the lung wall area,
      lung wall template matching (LWTM), where semicircular models were used as
      reference patterns; the semicircular models were rotated according to the angle
      of the target point on the contour of the lung wall. After initial detecting
      candidates using the two template-matching methods, we extracted a total of 13
      feature values and used them to eliminate false-positive findings. Twenty
      clinical cases involving a total of 557 sectional images were used in this study.
      71 nodules out of 98 were correctly detected by our scheme (i.e., a detection
      rate of about 72%), with the number of false positives at approximately
      1.1/sectional image. Our present results show that our scheme can be regarded as
      a technique for CAD systems to detect nodules in helical CT pulmonary images.

PMID- 11465467
TI  - Videoendoscopic distortion correction and its application to virtual guidance of
      endoscopy.
AB  - Modern video-based endoscopes offer physicians a wide-angle field of view (FOV)
      for minimally invasive procedures. Unfortunately, inherent barrel distortion
      prevents accurate perception of range. This makes measurement and distance
      judgment difficult and causes difficulties in emerging applications, such as
      virtual guidance of endoscopic procedures. Such distortion also arises in other
      wide FOV camera circumstances. This paper presents a distortion-correction
      technique that can automatically calculate correction parameters, without precise
      knowledge of horizontal and vertical orientation. The method is applicable to any
      camera-distortion correction situation. Based on a least-squares estimation, our
      proposed algorithm considers line fits in both FOV directions and gives a
      globally consistent set of expansion coefficients and an optimal image center.
      The method is insensitive to the initial orientation of the endoscope and
      provides more exhaustive FOV correction than previously proposed algorithms. The
      distortion-correction procedure is demonstrated for endoscopic video images of a
      calibration test pattern, a rubber bronchial training device, and real human
      circumstances. The distortion correction is also shown as a necessary component
      of an image-guided virtual-endoscopy system that matches endoscope images to
      corresponding rendered three-dimensional computed tomography views.

PMID- 11465468
TI  - A computationally efficient algorithm for determining regional cerebral blood
      flow in heterogeneous tissues by positron emission tomography.
AB  - Inclusion of brain tissues with different rates of blood flow and metabolism
      within a voxel or region of interest is an unavoidable problem with positron
      emission tomography due to its limited spatial resolution. Because regional
      cerebral blood flow (rCBF) is higher in gray matter than in white matter, the
      partial volume effect leads to underestimation of rCBF in gray matter when rCBF
      in the region as a whole is determined. Furthermore, weighted-average rCBF itself
      is underestimated if the kinetic model used in the analysis fails to account for
      the tissue heterogeneity. We have derived a computationally efficient method for
      estimating both gray matter and weighted-average rCBF in heterogeneous tissues
      and validated the method in simulation studies. The method is based on a model
      that represents a heterogeneous tissue as a weighted mixture of two homogeneous
      tissues. A linear least squares algorithm is used to estimate the model
      parameters.

PMID- 11465469
TI  - The design and implementation of COSEM, an iterative algorithm for fully 3-D
      listmode data.
AB  - In this paper,we present coincidence-list-ordered sets expectation-maximization
      (COSEM), an algorithm for iterative image reconstruction directly from list-mode
      coincidence acquisition data. The COSEM algorithm is based on the ordered sets EM
      algorithm for binned data but has several extensions that makes it suitable for
      rotating two planar detector tomographs. We develop the COSEM algorithm and
      extend it to include analytic calculation of detection probability, noise
      reducing iterative filtering schemes, and on-the-fly attenuation correction
      methods. We present an adaptation of COSEM to the Varicam?VG camera and show
      results from clinical and phantom studies.

PMID- 11465470
TI  - Space-time segmentation using level set active contours applied to myocardial
      gated SPECT.
AB  - This paper presents a new variational method for the segmentation of a moving
      object against a still background, over a sequence of [two-dimensional or three
      dimensional (3-D)] image frames. The method is illustrated in application to
      myocardial gated single photon emission computed tomography (SPECT) data, and
      incorporates a level set framework to handle topological changes while providing
      closed boundaries. The key innovation is the introduction of a geometrical
      constraint into the derivation of the Euler-Lagrange equations, such that the
      segmentation of each individual frame can be interpreted as a closed boundary of
      an object (an isolevel of a set of hyper-surfaces) while integrating information
      over the entire sequence. This results in the definition of an evolution velocity
      normal to the object boundary. Applying this method to 3-D myocardial gated SPECT
      sequences, the left ventricle endocardial and epicardial limits can be computed
      in each frame. This space-time segmentation method was tested on simulated and
      clinical 3-D myocardial gated SPECT sequences and the corresponding ejection
      fractions were computed.

PMID- 11465471
TI  - Addendum: B-spline interpolation in medical image processing.
AB  - This paper analyzes B-spline interpolation techniques of degree 2, 4, and 5 with
      respect to all criteria that have been applied to evaluate various interpolation
      schemes in a recently published survey on image interpolation in medical imaging
      (Lehmann et al., 1999). It is shown that high-degree B-spline interpolation has
      superior Fourier properties, smallest interpolation error, and reasonable
      computing times. Therefore, high-degree B-splines are preferable interpolators
      for numerous applications in medical image processing, particularly if high
      precision is required. If no aliasing occurs, this result neither depends on the
      geometric transform applied for the tests nor the actual content of images.

PMID- 11465472
TI  - Segmentation of large brain lesions.
AB  - This paper describes a region-growing algorithm for the segmentation of large
      lesions in T1-weighted magnetic resonance (MR) images of the head. The algorithm
      involves a gray level similarity criterion to expand the region and a size
      criterion to prevent from over-growing outside the lesion. The performance of the
      algorithm is evaluated and validated on a series of pathologic three-dimensional
      MR images of the head.

PMID- 11465473
TI  - Electron Microscopy What Izzits revisited: an Ultrapath X quiz.
AB  - The authors present 18 cases of various nature, representing a wide spectrum of
      neoplastic and nonneoplastic diseases shown at Ultrapath X in quiz format for
      identification or diagnosis.

PMID- 11465474
TI  - Ultrastructural  aspects of autoschizis: a new cancer cell death induced by the
      synergistic action of ascorbate/menadione on human bladder carcinoma cells.
AB  - Scanning and transmission electron microscopy were employed to further
      characterize the cytotoxic effects of a ascorbic acid/menadione (or vitamin
      C/vitamin K3) combination on a human bladder carcinoma T24 cell line. Following 1
      h treatment T24 cells display membrane and mitochondrial defects as well as
      excision of cytoplasmic fragments that contain no organelles. These continuous
      self-excisions reduce the cell size. Concomitant, nuclear changes, chromatin
      disassembly, nucleolar condensation and fragmentation, and decreased nuclear
      volume lead to cell death via a process similar to karyorrhexis and karyolysis.
      Because this cell death is achieved through a progressive loss of cytoplasm due
      to self-morsellation, the authors named this mode of cell death autoschizis (from
      the Greek autos, self, and schizein, to split, as defined in Scanning. 1998; 20:
      564-575). This morphological characterization of autoschizic cell death confirms
      and extends the authors previous reports and demonstrates that this cell death is
      distinct from apoptosis.

PMID- 11465475
TI  - Alport disease: a review of the diagnostic difficulties.
AB  - In patients with familial hematuria, ultrastructural study of the renal biopsy
      has been the gold standard for the diagnosis of Alport disease, based on
      characteristic findings of glomerular basement membrane thickening due to
      reduplication of the lamina densa. But the diagnosis has difficulties as not all
      biopsies from Alport disease patients have these structural changes. In adult
      female patients or in children, extensive thinning of the basement membrane can
      be the major abnormality by electron microscopy. Until the genetic mutation of
      collagen IV responsible for Alport disease can be demonstrated in all patients,
      the diagnosis will continue to be a challenge at the clinical and at the
      ultrastructural levels.

PMID- 11465476
TI  - Immunoelectron microscopy on material retrieved from paraffin: accurate sampling
      on the basis of stained paraffin sections.
AB  - As a rule, immunoelectron microscopy (immuno-EM) is performed on fresh material
      processed according to specialized methods (e.g., freezing or embedding in
      hydrophilic resins). Paraffin-embedded tissue has only occasionally been used as
      a source of material for immuno-EM; this was usually as a last resort, when no
      fresh material was available. The authors used archival formalin-fixed, paraffin
      embedded basal cell carcinomas for studying the fine-structural distribution of
      the cell surface molecule CD44 and its variants, as well as some other antigens.
      The results demonstrate, firstly, that paraffin-embedded material is far more
      suitable for immuno-EM than frequently assumed and, secondly, that the use of
      paraffin-embedded material enables highly accurate sampling on the basis of
      immunohistochemically or conventionally stained light microscopic sections.

PMID- 11465477
TI  - Spindle cell carcinoids of the lung with paraganglioid features: a reappraisal of
      their histogenetic origin from paraganglia using immunohistochemical and
      electronmicroscopic techniques.
AB  - Five cases of spindle cell carcinoids of the lung were analyzed by
      immunohistochemical and ultrastructural technique. They were found to be biphasic
      tumors composed of the major component of neuroendocrine cells (chief cells) and
      a minor component of dendritic cells (supporting cells). The chief cells
      displayed positivity for neuroendocrine phenotypic antigenic markers: neuron
      specific enolase (NSE), chromogranin A, and synaptophysin. They contained varying
      numbers of dense-core granules by electron microscopy. In addition, the chief
      cells expressed cytoplasmic positivity for cytokeratins. The supporting cells
      were dendritic in appearance and displayed strong positivity for S-100 protein in
      all cases. Glial fibrillary acidic protein was positive in two cases. On electron
      microscopy, the supporting cells were agranular and found along the external
      lamina surrounding the nests of tumor cells. In two cases, rare ganglion cell
      like cells were present. The histomorphologic, immunohistochemical, and
      ultrastructural features were contrastingly different from the classical
      pulmonary carcinoid and rather resembled gangliocytic paragangliomas arising from
      small intestine and spine. It is proposed that pulmonary carcinoids with biphasic
      features are better designated as gangliocytic paragangliomas of the lung rather
      than paraganglioid carcinoids.

PMID- 11465478
TI  - Immunohistochemical and ultrastructural investigation of neural differentiation
      in Ewing sarcoma/PNET of bone and soft tissues.
AB  - The authors evaluated the role of immunohistochemistry and electron microscopy in
      defining neural differentiation in 28 cases of Ewing sarcoma/PNET. The panel of
      primary antibodies used included vimentin, MIC-2, NSE, S-100 protein, leu7,
      neurofilaments, GFAP, and chromogranin A. Cases were considered undifferentiated
      when neural markers were absent, poorly differentiated if one neural marker was
      present, and well differentiated if two or more markers were observed. Cases were
      also evaluated for the presence of cytoplasmic processes, microtubules, and
      neurosecretory granules as ultrastructural features of neural differentiation:
      the tumor was classified as well differentiated if two of these features were
      present; and poorly differentiated if one was evident; all other cases were
      considered undifferentiated. According to immunohistochemistry, 10 cases (35.7%)
      were undifferentiated, 12 cases (42.9%) were poorly differentiated, and 6 (21.4%)
      were well differentiated. According to the ultrastructural analysis, 10 tumors
      were undifferentiated (35.7%), 14 poorly differentiated (50%), and 4 well
      differentiated (14.3%). The overall concordance between the two techniques was
      low (35.7%), and both modalities were concordant in classifying only 1 well
      differentiated, 5 poorly differentiated, and 4 undifferentiated tumors. In
      conclusion, the authors suggest that investigations devoted to test the
      prognostic significance of neural differentiation in these neoplasms should
      employ both immunohistochemistry and electron microscopy, separately and in
      combination, to assess what is the most effective choice for predicting the
      clinical course.

PMID- 11465479
TI  - Pituitary carcinoma: an ultrastructural study of eleven cases.
AB  - Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that
      undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing.
      Their ultrastructural features, particularly relative to benign adenomas of
      similar functional type, have not been sufficiently explored. Eleven cases of
      immunohistochemically characterized pituitary carcinoma with documented
      cerebrospinal and/or systemic metastases were collected from various institutions
      and studied by transmission electron microscopy. The tumors were surgically
      removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50
      years). All were endocrinologically functioning. Six tumors secreted PRL; three
      were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with
      the ACTH-producing tumors had all presented with Cushing's disease and two of
      them had undergone adrenalectomy (Nelson syndrome). In most cases significant
      cellular atypia and mitotic activity were observed. In terms of morphologic
      features of functional differentiation, electron microscopy revealed that in 9
      cases the tumor cells maintained at least some ultrastructural markers of their
      basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture
      of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2
      cases, both PRL-producing carcinomas, the cell type comprising the tumor could
      not be identified on an ultrastructural basis alone. Ultrastructural
      investigation of pituitary carcinomas confirms their endocrine nature and, in
      most but not all cases, reveals their functional differentiation. Despite the
      diagnostic utility of electron microscopy in the assessment of these rare tumors,
      the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly
      made on ultrastructural grounds alone.

PMID- 11465480
TI  - As you like it, Part 3: A critique and historical review of calcification as seen
      with the electron microscope.
AB  - As You Like It, Part 3, is a continuation of the lectures given by the author
      (Ultra Path VIII and Ultra Path IX). It is a critical historical review of topics
      of interest to electron microscopists, attempting to show what went wrong and
      perhaps also why. The topics chosen this time demonstrate the prominent role
      electron microscopy has played in elucidating the diverse ways in which
      calcification can occur. The classic concept of dystropic and metastatic
      calcification is now inadequate to explain all observed phenomena. The electron
      microscope shows that calcification occurs in many different intracellular and
      extracellular sites and that each has its own morphology and etiology. Thus, a
      new classification based on ultrastructural morphology is born, but few seem to
      be aware of it. The author examines the ubiquitous but not too well-known
      phenomenon of cell remodeling, which often, but not always, leads to
      calcification. Topics are presented under the following headings: (1) matrical
      lipidic debris, (2) spherical microparticles, (3) matrix vesicles, (4)
      intramitochondrial calcification, (5) intralysosomal calcification, (6)
      calcification of collagen, (7) calcification of elastic fibers, and (8)
      calcification of secretory products.

PMID- 11465481
TI  - Primary pulmonary rhabdomyosarcoma: report of a case in an adult and review of
      the literature.
AB  - A case of primary pulmonary rhabdomyosarcoma occurring in a 62-year-old man is
      reported, and a review of the literature is presented. The tumor affected the
      left upper lobe and involved the mediastinal lymph nodes. Immunohistochemical and
      ultrastructural studies supported the myogenic phenotype of the neoplasm. A left
      pneumonectomy was performed with complete surgical removal of the tumor.
      Postoperative radiotherapy was carried out. The patient is currently alive and
      free of disease 9 months after operation. Despite the rarity of primary pulmonary
      rhabdomyosarcoma, this tumor should be differentiated from other poorly
      differentiated pulmonary neoplasms and from metastatic sarcomas.

PMID- 11465482
TI  - Microvillous inclusion disease: report of a case with atypical features.
AB  - Microvillous inclusion disease is a rare lethal disorder characterized by
      intractable, severe, watery diarrhea beginning in early infancy. The underlying
      defect is thought to be an autosomal recessive genetic abnormality resulting in
      defective brush-border assembly and differentiation. Normally, this diagnosis is
      easily established through the electron microscopic demonstration of
      characteristic microvilli-lined inclusions lying within the apical cytoplasm of
      surface enterocytes. In a small number of patients appearing to have microvillous
      inclusion disease it has not proven possible to demonstrate the typical
      inclusions. The existence of another entity, termed intestinal microvillous
      dystrophy, has been proposed to account for such occurrences. This assertion was
      founded in large part upon the observation that the few subjects studied all
      displayed a slightly atypical clinical presentation. The case now being presented
      exhibited the morphologic features ascribed to intestinal microvillous dystrophy
      but had a clinical presentation that was entirely typical of microvillous
      inclusion disease. It serves thus to conceptually unite intestinal microvillous
      dystrophy with microvillous inclusion disease.

PMID- 11465483
TI  - Electrophoretic mobility of a particle covered with an ion-penetrable membrane.
AB  - The electrophoretic behavior of a planar particle covered by an ion-penetrable
      membrane, which simulates a biological entity, is investigated. We show that, in
      general, a point charge model will overestimate the electrophoretic mobility of a
      particle and the deviation increases with the increase in the concentration of
      fixed charge and with the decrease in the thickness of membrane layer. As in the
      case of a point charge model, the present model also predicts a local maximum in
      the absolute mobility as the thickness of membrane layer varies. If the sizes of
      counterions of various valences are the same, then the lower the valence of
      counterions, the larger the mobility, and the larger the counterions, the greater
      the mobility. The latter is consistent with the experimental observations in the
      literature. For the level of the concentration of fixed charge examined, the
      effect of coions on the mobility is negligible.

PMID- 11465484
TI  - An immunoblotting method for high-resolution isoelectric focusing of protein
      isoforms on immobilized pH gradients.
AB  - Post-translational modifications such as phosphorylation and acetylation are
      important elements for regulating the activity of enzymes or structural proteins.
      These modifications give rise to isoforms that are often not resolved by
      separation methods relying on the size of proteins. Here, we optimized an
      isoelectric focusing (IEF)-immunoblotting method suitable for analyzing protein
      isoforms in total cell extracts. The separations were carried out in parallel on
      commercially available immobilized pH gradient slab gels (IPG). The buffer used
      for separation contained urea, thiourea, dithiothreitol, as well as the detergent
      3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate (CHAPS), and was
      designed to match those used in two-dimensional polyacrylamide gel
      electrophoresis (PAGE) separations where efficient solubilization is required.
      Proteins were transferred to membranes by passive diffusion in the presence of 4
      M guanidinium chloride using protocols optimized for several protein classes
      (tubulin, stathmin, 14-3-3 proteins) some of which required removal of CHAPS
      prior to transfer. In conjunction with narrow-range pH gradient gels, excellent
      resolution of isoforms differing by phosphorylation or acetylation was achieved.
      The usefulness of pI and titration curve calculations for predicting the pI
      shifts expected for post-translational modifications of proteins with known amino
      acid composition was demonstrated. Using stathmin--which contains four
      phosphorylation sites--as an example, the effects on the pI-shifts were well
      predicted. This sensitive and widely applicable IEF-blotting technology is
      expected to be especially suited for analyzing protein isoforms first detected by
      two-dimensional electrophoresis.

PMID- 11465485
TI  - Simultaneous immunoblotting analysis with activity gel electrophoresis in a
      single polyacrylamide gel.
AB  - We describe here that a simple diffusion blotting method can couple
      immunoblotting analysis with another biochemical technique in a single
      polyacrylamide gel. The efficiency of protein transfer was evaluated by serial
      dilutions of nephrosin, a metalloproteinase of the astacin family, and by
      immunodetection. It is estimated that diffusion blotting produces 25-50% of the
      signal intensity compared to the classical electrophoretic transfer method.
      However, with diffusion blotting it is possible to generate several replicas from
      a single gel. In addition, a protein blot can be obtained from a sodium dodecyl
      sulfate (SDS)-polyacrylamide gel for zymography assay or from a native
      polyacrylamide gel for electrophoretic mobility shift assay (EMSA). In this
      regard, a particular signal in zymography or EMSA can be confirmed by
      simultaneous immunoblotting analysis with a corresponding antiserum. Therefore,
      diffusion blotting allows a direct comparison of signals between gels and
      replicas in zymography assay and EMSA. These advantages make diffusion blotting
      desirable when partial loss of transfer efficiency can be tolerated or be
      compensated by a more sensitive immunodetection reaction using enhanced
      chemiluminescence substrates.

PMID- 11465486
TI  - A rapid and efficient two-step gel electrophoresis method for the purification of
      major rye grass pollen allergens.
AB  - Purified proteins are mandatory for molecular, immunological and cellular
      studies. However, purification of proteins from complex mixtures requires
      specialised chromatography methods (i.e., gel filtration, ion exchange, etc.)
      using fast protein liquid chromatography (FPLC) or high-performance liquid
      chromatography (HPLC) systems. Such systems are expensive and certain proteins
      require two or more different steps for sufficient purity and generally result in
      low recovery. The aim of this study was to develop a rapid, inexpensive and
      efficient gel-electrophoresis-based protein purification method using basic and
      readily available laboratory equipment. We have used crude rye grass pollen
      extract to purify the major allergens Lol p 1 and Lol p 5 as the model protein
      candidates. Total proteins were resolved on large primary gel and Coomassie
      Brilliant Blue (CBB)-stained Lol p 1/5 allergens were excised and purified on a
      secondary "mini"-gel. Purified proteins were extracted from unstained separating
      gels and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) and immunoblot analyses. Silver-stained SDS-PAGE gels resolved pure
      proteins (i.e., 875 microg of Lol p 1 recovered from a 8 mg crude starting
      material) while immunoblot analysis confirmed immunological reactivity of the
      purified proteins. Such a purification method is rapid, inexpensive, and
      efficient in generating proteins of sufficient purity for use in monoclonal
      antibody (mAb) production, protein sequencing and general molecular,
      immunological, and cellular studies.

PMID- 11465487
TI  - Improvement of base-calling in multilane automated DNA sequencing by use of
      electrophoretic calibration standards, data linearization, and trace alignment.
AB  - We present a new method for the linearization and alignment of data traces
      generated by multilane automated DNA sequencing instruments. Application of this
      method to data generated with the Visible Genetics Open Gene DNA sequencing
      system (using MicroCel 700 gel cassettes, with a 25 cm separation distance)
      allows read lengths of > 1,000 nucleotides to be routinely obtained with high
      confidence and > 97% accuracy. This represents an increase of 10-15% in average
      read length, relative to data from this system that have not been processed in
      the fashion described herein. Most importantly, the linearization and alignment
      method allows usable sequence to be obtained from a fraction of 10-15% of data
      sets which, because of original trace misalignment problems, would otherwise have
      to be discarded. Our method involves adding electrophoretic calibration standards
      to the DNA sequencing fragments. The calibration standards are labeled with a dye
      that differs spectrally from the dye attached to the sequencing fragments. The
      calibration standards are identical in all the lanes. Analysis of the mobilities
      of the calibration standards allows correction for both systematic and random
      variation of electrophoretic properties between gel lanes. We have successfully
      used this method with two-dye and three-dye DNA sequencing instruments.

PMID- 11465488
TI  - Multiple use of slab gels in sequencing apparatus for separation of polymerase
      chain reaction products.
AB  - Attempting to assess whether a decrease of the electrophoresis temperature could
      prevent or reduce the extent of gel well deformations, and whether the
      utilization of native polyacrylamide gels (without urea) could speed up the
      separation of polymerase chain reaction (PCR)-amplified products with an
      automated 377 DNA sequencer, denatured PCR products were subjected to
      electrophoresis in 6% native gels under 45 degrees C. Results show that a
      decrease of the electrophoresis temperature from 51 degrees C (recommended by the
      User's Manual) to 45 degrees C substantially facilitates the preservation of gel
      wells, and that all PCR products tested migrate significantly faster in native
      than in denatured (with urea) gels of the same concentration. The combination of
      a 6% native gel and a lower (45 degrees C) electrophoresis temperature permits
      multiple uses of a given gel with consistent results, consequently reducing the
      electrophoresis time and reagent costs.

PMID- 11465489
TI  - Use of denaturing gradient gel electrophoresis to detect mutation in VS2 of the
      16S-23S rDNA spacer amplified from Staphylococcus aureus isolates.
AB  - To develop a double gradient denaturing gradient gel electrophoresis (DG-DGGE)
      based typing method that rapidly and accurately types clinical isolates of
      Staphylococcus aureus, the VS2 region of the 16S-23S rRNA spacer region (ISR) was
      chosen because of its potential high variation. The VS2 region was amplified with
      a 40-mer GC-clamp attached to the 5'-end of the reverse primer. The 145 bp PCR
      product was then separated by DG-DGGE using denaturant concentrations of 25-40%
      and polyacrylamide concentrations of 6-12%. Of the five mutations identified in
      336 S. aureus isolates, one mutation was found to be highly specific for 161/171
      (94%) of methicillin-resistant S. aureus (MRSA) isolates from different
      geographic locations and isolation times. This same mutation was found in 15/160
      (9%) of penicillin- or methicillin-sensitive S. aureus isolates. In some isolates
      two mutations occured together in the one genome suggesting some S. aureus
      isolates have two copies of VS2. In these 336 isolates nine genotypes with
      different combinations of the five mutations were identified. In 18 coagulase
      negative staphylococci (CNS), the MRSA-specific mutation was found along with two
      other mutations in all isolates demonstrating consistent differences in the
      presence of these mutations between CNS and S. aureus. The marked differences in
      VS2 sequences found between MRSA, methicillin- or penicillin-sensitive S. aureus
      (SSA), and CNS by DGGE in the present study may be useful in evolutionary studies
      and in the development of a specific assay for MRSA from clinical specimens.

PMID- 11465490
TI  - Single-strand conformation polymorphism analysis of genetic variation in
      Labiostrongylus longispicularis from kangaroos.
AB  - Single-strand conformation polymorphism (SSCP) analysis was employed to screen
      for sequence heterogeneity in the second internal transcribed spacer (ITS-2) of
      ribosomal (r) DNA of Labiostrongylus longispicularis, a parasitic strongylid
      nematode occuring in some species of kangaroo in different geographical regions
      of Australia. The results showed that most of the nematodes screened had
      different SSCP profiles, which were subsequently shown to correspond to
      polymorphisms and/or an indel in the ITS-2 sequence. These variable sites related
      mainly to unpaired regions of the predicted secondary structure of the precursor
      rRNA molecule. SSCP profiles could be used to distinguish L. longispicularis in
      Macropus robustus robustus (New South Wales) from L. longispicularis in Macropus
      robustus erubescens and Macropus rufus (South Australia). This difference
      corresponded to a transversional change in the ITS-2 sequence at alignment
      position 82. The study demonstrated clearly the effectiveness of SSCP analysis
      for future large-scale population genetic studies of L. longispicularis in order
      to test the hypothesis that L. longispicularis from different geographical
      regions represents multiple sibling species.

PMID- 11465491
TI  - Electrophoretic detection of population variation within Contracaecum ogmorhini
      (Nematoda: Ascaridoidea: Anisakidae).
AB  - This study examined genetic variation among specimens of Contracaecum ogmorhini
      from different otariid hosts and geographical origins using a polymerase chain
      reaction (PCR)-based mutation detection approach. The first (ITS-1) and second
      (ITS-2) internal transcribed spacers (ITS) of ribosomal DNA (rDNA) were amplified
      individually by PCR, scanned for sequence variation by single-strand conformation
      polymorphism (SSCP), and samples displaying variable SSCP profiles were subjected
      to cycle sequencing. While C. ogmorhini individuals from Arctocephalus pusillus
      pusillus (CoAPP) from South Africa and those from Arctocephalus pusillus
      doriferus (CoAPD) from Australia had very similar SSCP profiles for both ITS-1
      and ITS-2, individuals of C. ogmorhini from Zalophus californianus (CoZC) from
      Pacific Canada could be unequivocally distinguished based on their profiles. In
      accordance with SSCP results, both CoAPP and CoAPD had identical ITS consensus
      sequences, whereas CoZC differed in sequence from both CoAPP and CoAPD
      populations by 0.2% (one base in the ITS-1) and 0.7% (two bases in the ITS-2).
      Based on the nucleotide difference in the ITS-2 sequence, a PCR-linked
      restriction fragment length polymorphism (RFLP) could be employed to distinguish
      individuals representing CoZC from those of both CoAPP and CoAPD. The findings
      suggest that C. ogmorhini may represent a complex of at least two species.

PMID- 11465492
TI  - Automated detection of differently expressed fragments in mRNA differential
      display.
AB  - We present a novel method for the automated detection of fragments showing
      dissimilar expression in mRNA differential display. The analysis is based on
      aligning the numerical electrophoretic lane data in respect of a given distance
      function defined on a set of fragments, or signal peaks in general. We presume
      that significant dissimilarities between peaks result in extreme score values
      computed for aligned peak pairs. Whereas in sequence comparison, an overall
      sequence similarity score is conventionally used, the current method defines a
      special dissimilarity score for searching the peak pairs showing the largest
      relative differences between the lanes. The output of the analysis is a highly
      reduced list of peak pairs, along with a set of associated features extracted
      from the lanes. Only the peaks of this list need to be visually confirmed instead
      of the vast amount of peaks in the original electrophoretic results. The results
      obtained by the algorithm correlate well with results of visual evaluation of the
      same electropherograms. The current algorithm may be applied to the study of
      complex expression patterns in multiple lanes and, in general, to automated
      recognition of variously defined patterns of quantitative electrophoretic data.

PMID- 11465493
TI  - Notl-Msell methylation-sensitive amplied fragment length polymorhism for DNA
      methylation analysis of human cancers.
AB  - We have applied a methylation-sensitive restriction endonuclease, NotI, to the
      existing amplified fragment length polymorphism (AFLP) method and developed NotI
      MseI methylation-sensitive-AFLP (MS-AFLP). NotI-MseI MS-AFLP allows the analysis
      of DNA methylation alterations at the NotI sites scattered over the genome.
      Hypermethylation and hypomethylation are visualized by the decrease and increase
      in the band intensity of DNA fingerprints. Identification of consistent changes
      can be facilitated through parallel electrophoresis of multiple samples. DNA
      fragments exhibiting alterations can be cloned from fingerprint bands by
      amplification of gel-eluted DNA with the same pair of primers used for
      radioactive fingerprint presentation. Fluorescent NotI-MseI MS-AFLP offers a
      safer method of studying the alterations in DNA methylation, and may be applied
      to the hybridization of DNA microarrays in the future. Using NotI-MseI MS-AFLP,
      we observed frequent hypomethylation of a satellite DNA repeat sequence in a
      majority of breast tumors.

PMID- 11465494
TI  - Influence of neutral cyclodextrin concentration on plate numbers in capillary
      electrophoresis.
AB  - A quantitative theory of plate number N in capillary electrophoresis was
      developed for buffers containing neutral cyclodextrins (CDs) capable of forming
      inclusion complexes. In the theory, N was modeled by longitudinal diffusion,
      injection extent, width of the detection window, and the detector time constant.
      The apparent mobility was modeled as a weighted sum of the mobilities of the free
      solution analyte and the inclusion complex. The apparent diffusion coefficient
      was modeled as a similarly weighted sum. Both the apparent mobility and diffusion
      coefficient were corrected by functions that compensated for increases of buffer
      temperature caused by Joule heat. The experimental N's and apparent mobilities of
      neutral thiourea and of the anions, dansyl D- and L-leucine, dansyl D- and L
      aspartic acid, benzoate, and 4-nitrophenolate, were determined in buffers
      containing from 0 to 15 mM beta-CD. The binding constants, and mobilities and
      diffusion coefficients of the free-solution analyte and inclusion complex, were
      calculated as regression coefficients by fitting theory to these determinations.
      The regression coefficients were shown to have physicochemical meaning, as
      assessed by literature values, independent measurements, and theoretical
      predictions. The assessment showed the Nernst-Einstein equation does not relate
      mobilities and diffusion coefficients at the electrolyte concentration used. The
      interdependence of mobilities, diffusion coefficients, binding constants, and
      other dispersion sources was interpreted to evaluate the factors affecting the
      variation of N with CD concentration. From the interpretation, an approximate
      equation for N in low-concentration CD buffers was derived. The equation depends
      on free-solution and inclusion-complex mobilities and diffusion coefficients, the
      binding constant, the potential difference over the effective capillary length,
      and the number of plates in a CD-free buffer.

PMID- 11465495
TI  - Practical evaluation of the influence of excessive sample concentration on the
      estimation of dissociation constants with affinity capillary electrophoresis.
AB  - A practical approach for the evaluation of binding constants with affinity
      capillary electrophoresis (ACE) is presented using the different linear and
      nonlinear regression methods. The influence of the sample concentration on the
      different obtained curves is depicted and it is shown that the different
      representations should always be compared. The well-known strong molecular
      interaction between the macrocyclic antibiotic vancomycin and a (D)-Ala-(D)-Ala
      terminating peptide is used as model in this study.

PMID- 11465496
TI  - Nonradiochemical DNase I footprinting by capillary electrophoresis.
AB  - A new application for DNase I footprinting using capillary electrophoresis (CE)
      has been developed in order to decrease analysis time and to eliminate the use of
      radiochemicals. An additional advantage of the new method over the traditional
      radioactive methods is that the DNA probe can be labeled on both ends with
      different fluorescein dyes. This provides an internal check of the identification
      of protein-binding sites on DNA, because the binding region can be observed from
      both DNA strands. The initial parameters for the CE method were developed using
      the Promega Core Footprinting Kit for analysis of AP-2 binding sites in the SV40
      enhancer sequence. After optimization of the method, the protocol was found to be
      effective for footprint analysis of the immediate upstream region (bases -1 to 
      370) of the rat glutathione peroxidase (GPX) and it permitted identification of a
      previously unknown binding site in the upstream sequence of the GPX gene.

PMID- 11465497
TI  - Fast DNA sequencing up to 1,000 bases by capillary electrophoresis using poly(N,N
      dimethylacrylamide) as a separation medium.
AB  - Poly(N,N-dimethylacrylamide) (PDMA) with a molecular mass of 5.2 x 10(6) g/mol
      has been synthesized and used in DNA sequencing analysis by capillary
      electrophoresis (CE). A systematic investigation is presented on the effects of
      different separation conditions, such as injection amount, capillary inner
      diameter, polymer concentration, effective separation length, electric field and
      temperature, on the resolution. DNA sequencing up to 800 bases with a resolution
      (R) limit of 0.5 (and 1,000 bases with a resolution limit of 0.3) and a migration
      time of 96 min was achieved by using 2.5% w/v polymer, 150 V/cm separation
      electric field, and 60 cm effective separation length at room temperature on a
      DNA sample prepared with FAM-labeled--21M13 forward primer on pGEM3Zf(+) and
      terminated with ddCTP. Ultrafast and fast DNA sequencing up to 420 and 590 bases
      (R > or = 0.5) were also achieved by using 3% w/v polymer and 40 cm effective
      separation length with a separation electric field of 525 and 300 V/cm, and a
      migration time of 12.5 and 31.5 min, respectively. PDMA has low viscosity, long
      shelf life and dynamic coating ability to the glass surface. The unique
      properties of PDMA make it a very good candidate as a separation medium for large
      scale DNA sequencing by capillary array electrophoresis (CAE).

PMID- 11465498
TI  - Clay-enhanced DNA separation in low-molecular-weight poly(N,N-dimethylacrylamide)
      solution by capillary electrophoresis.
AB  - The effect of the separation medium in capillary electrophoresis consisting of a
      low-molecular-mass poly(N,N-dimethylacrylamide) (PDMA) solution on the DNA
      separation by adding a small amount of montmorillonite clay into the polymer
      matrix is presented. On the separation of the pBR322/HaeIII digest, both the
      resolution and the efficiency were increased by adding 2.5-5.0 x 10(-5) g/mL clay
      into the 5% w/v PDMA with a molecular mass of only 100 K. Moreover, there was no
      increase in the migration time of DNA fragments. Similar results were observed by
      using a C-terminated pGEM-3Zf(+) sequencing DNA sample in a sequencing buffer.
      Experimental data also showed that the addition of clay increased the viscosity
      of the polymer solution. We attribute this effect to the structural change of the
      polymer matrix caused by the exfoliated clay sheets, whereby the thin clay sheets
      function like a "dynamic cross-linking plate" for the PDMA chains and effectively
      increase the apparent molecular mass of PDMA.

PMID- 11465499
TI  - Micellar electrokinetic capillary chromatography for the determination of Viagra
      and its metabolite (UK-103,320) in human serum.
AB  - Micellar electrokinetic capillary chromatography (MEKC) was investigated for the
      determination of Viagra (sildenafil citrate, SC) and its metabolite (UK-103,320)
      in human serum in a concentration range of clinical interest. For MEKC, human
      serum samples spiked with SC and UK were obtained directly after elution with
      methanol from a tC18 cartridge. The extract was evaporated and regenerated in a
      solution 1 mM of phosphate buffer (pH 12.3) which contained a methanol percentage
      of 20% that was analyzed using phosphate buffer (pH 12.3, 10 mM) containing 30 mM
      sodium dodecyl sulfate (SDS) as separation electrolyte and a fused-silica
      capillary. This method gave satisfactory interday precision with respect to
      migration times relative standard deviation (RSD < 1%) and linear responses for
      the concentration ranges investigated (0.50-3.50 mg L(-1) for the compound SC and
      0.90-4.60 mg L(-1) for UK). An intraday RSD (n = 5 graphs) between the slopes of
      the calibration graphs was acceptable (6.40%) for SC and (3.37%) for UK. A
      satisfactory interday precision between slopes was also obtained (RSD 4.10% for
      SC and a RSD 2.72% for UK) which demonstrated the ruggedness of this method.
      Detection limits (S/N = 3) were about 200 ng/mL for both compounds in human
      serum. MEKC was shown as a good method with regards to simplicity, precision and
      sensitivity.

PMID- 11465500
TI  - Determination of urea-derived pesticides in fruits and vegetables by solid-phase
      preconcentration and capillary electrophoresis.
AB  - A multiresidue analytical method based on solid-phase extraction (SPE) enrichment
      combined with capillary electrophoresis (CE), using micellar electrokinetic
      capillary chromatography (MEKC), was developed to determine ten substituted urea
      pesticides in orange and tomato samples. Several factors such as pH, composition
      and concentration of the buffer, concentration of surfactant, addition of organic
      solvent, and working voltage were optimized to obtain the best compound
      separation in the shortest time. Separation can be achieved in 7 min using a
      micellar aqueous pH 9 buffer composed of 4 mM borate and 35 mM sodium dodecyl
      sulfate. After an SPE procedure, which provided a 10-fold enrichment, the limit
      of detection was about 0.05 mg kg(-1), which is in the order of the maximum
      residue limits (MRLs) established by the European Union (EU) for most of these
      compounds. Increasing the enrichment factor by using a larger amount of sample is
      difficult in oranges due to the matrix interferences, but is possible in
      tomatoes, which gave cleaner extracts and easily reached a 25-fold enrichment
      factor. The procedure involving SPE and CE provided acceptable recoveries (ranged
      42-118%) and relative standard deviations (RSDs; < 19%) at levels between 0.3 and
      5 mg kg(-1).

PMID- 11465501
TI  - Separation and determination of homologues of linear alkylbenzenesulfonates by
      nonaqueous capillary zone electrophoresis using alkylammonium salts in ethanol.
AB  - The separation of linear alkylbenzene sulfonates (LAS) by nonaqueous capillary
      electrophoresis (NACE) using negative polarity, and a buffer containing acetic
      acid and an alkylamine in nonaqueous ethanol, has been investigated. Several
      primary, secondary, and tertiary alkylamines with alkyl chains of different
      length were compared. The solutes travelled against the electroosmotic flow
      (EOF), and at the same time were braked by association with the alkylamine
      molecules or with the alkylammonium ions. The best resolution between adjacent
      LAS homologues (R approximately 2.1), partial isomer resolution in two peaks, and
      at the same time an excellent repeatability, was obtained with a small
      dipentylamine excess over the acetic acid. When the buffer concentration
      increased, resolution between the homologues increased slightly (R approximately
      2.4), and a different isomer group was partially separated. A background
      electrolyte (BGE) containing 10 mM acetic acid and 20 mM dipentylamine to
      separate and quantify the homologues within 25 min is recommended. The isomer
      peak profile with up to three peaks can be estimated using this buffer and
      another one with 80 mM acetic acid and 90 mM dipentylamine. The former BGE was
      used to determine LAS in liquid and powder laundry detergents. The detection
      limit for the determination of total LAS in these products was 2.5 microg mL(-1),
      and the peak area and migration time interday repeatabilities were below 4.3 and
      2.8%, respectively.

PMID- 11465502
TI  - Modeling and optimization of the chiral selectivity of basic analytes in chiral
      capillary electrophoresis with negatively charged cyclodextrins using
      electrochemical detection.
AB  - A mathematical model concerning the separation selectivity of basic analytes in
      chiral capillary electrophoresis (CE) modified with negatively charged
      cyclodextrins (CDs) has been presented to describe the dependence of chiral
      selectivity on the buffer pH and the chiral selector concentration. The
      electrophoretic method to determine the parameters of the model has also been
      developed. The model has been tested with racemic epinephrine and isoproterenol
      as target analytes and sulfonated beta-CD as chiral selector. The agreements have
      been found between the calculated and the measured values. Some significant
      conclusions to optimize chiral CE separation have been derived from the model and
      proven by the experiments. Electrochemical detection was used to meet the
      requirement of the low introduced concentration of analytes.

PMID- 11465503
TI  - Noninvasive picoliter volume thermometry based on backscatter interferometry.
AB  - Using the on-chip refractive index (RI) detector based on backscatter
      interferometry, sensitive, small volume, noninvasive thermometry can be
      performed. The current optical configuration for the on-chip interferometric
      backscatter detector (OCIBD) is quite simple and consists of an unfocused laser,
      an unaltered chip with a hemispherical channel and a photodetector. Alignment is
      straightforward with the only requirement being that the beam fully fills the
      channel. The interaction of an unfocused laser beam with the uncoated etched
      channel with a curvature within the silica plate (chip) produces fringes whose
      positional changes scale with respect to the refractive index (RI), n, of the
      fluid in the channel. Due to the inherently high value of dn/dT for most fluids
      and the high sensitivity of OCIBD to RI changes, the measurement of small
      temperature variations in sub-nanoliter volumes is possible. Performing OCIBD
      with a 75 microm diameter laser beam on a silica chip that contains an etched
      channel with a 40 microm radius facilitates noninvasive thermometry on a N-(2
      hydroxyethyl)piperazine-(2-ethanesulfonic acid) (HEPES) solution in a 188 x 10(
      12) L probe volume with a temperature resolution of 9.9 x 10(-4) degrees C, at
      the 99% confidence level.

PMID- 11465504
TI  - Attomole quantitation of protein separations with accelerator mass spectrometry.
AB  - Quantification of specific proteins depends on separation by chromatography or
      electrophoresis followed by chemical detection schemes such as staining and
      fluorophore adhesion. Chemical exchange of short-lived isotopes, particularly
      sulfur, is also prevalent despite the inconveniences of counting radioactivity.
      Physical methods based on isotopic and elemental analyses offer highly sensitive
      protein quantitation that has linear response over wide dynamic ranges and is
      independent of protein conformation. Accelerator mass spectrometry quantifies
      long-lived isotopes such as 14C to subattomole sensitivity. We quantified protein
      interactions with small molecules such as toxins, vitamins, and natural
      biochemicals at precisions of 1-5%. Micro-proton-induced X-ray emission
      quantifies elemental abundances in separated metalloprotein samples to nanogram
      amounts and is capable of quantifying phopsphorylated loci in gels. Accelerator
      based quantitation is a possible tool for quantifying the genome translation into
      proteome.

PMID- 11465505
TI  - Reduction and alkylation of proteins in preparation of two-dimensional map
      analysis: why, when, and how?
AB  - The standard procedure adopted up to the present in proteome analysis calls for
      just reduction prior to the isoelectric focusing/immobilized pH gradient
      (IEF/IPG) step, followed by a second reduction/alkylation step in between the
      first and second dimension, in preparation for the sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) step. This protocol is far from
      being optimal. It is here demonstrated, by matrix assisted laser
      desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry, that failure
      to reduce and alkylate proteins prior to any electrophoretic step (including the
      first dimension) results in a large number of spurious spots in the alkaline pH
      region, due to "scrambled" disulfide bridges among like and unlike chains. This
      series of artefactual spots comprises not only dimers, but an impressive series
      of oligomers (up to nonamers) in the case of simple polypeptides such as the
      human alpha- and beta-globin chains, which possess only one (alpha-) or two (beta
      ) -SH groups. As a result, misplaced spots are to be found in the resulting two
      dimensional (2-D) map, if performed with the wrong protocol. The number of such
      artefactual spots can be impressively large. In the case of analysis of complex
      samples, such as human plasma, it is additionally shown that failure to alkylate
      proteins results in a substantial loss of spots in the alkaline gel region,
      possibly due to the fact that these proteins, at their pI, regenerate their
      disulfide bridges with concomitant formation of macroaggregates which become
      entangled with and trapped within the polyacrylamide gel fibers. This strongly
      quenches their transfer in the subsequent SDS-PAGE step.

PMID- 11465506
TI  - Alkylation kinetics of proteins in preparation for two-dimensional maps: a matrix
      assisted laser desorption/ionization-mass spectrometry investigation.
AB  - All existing protocols for protein separation by two-dimensional (2-D) gel
      electrophoresis require the full reduction, denaturation, and alkylation as a
      precondition for an efficient and meaningful separation of such proteins.
      Existing literature provides a strong evidence to suggest that full reduction and
      denaturation can be achieved in a relatively short time; the same thing, however,
      can not be said for the alkylation process, which the present study shows that
      more than 6 h are required for a complete alkylation. We have used matrix
      assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF
      MS) to monitor protein alkylation by iodoacetamide over the period 0-24 h at pH
      9. The present, fast and specific MS method provided clear indication on the
      extent and speed of alkylation which reached approximately 70% in the first 2
      min, yet the remaining 30% resisted complete alkylation up to 6 h. The use of
      sodium dodecyl sulfate (SDS) during the alkylation step resulted in a strong
      quenching of this reaction, whereas 2% 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate (CHAPS) exerted a much reduced inhibition. The implications of
      the present measurements on 2-D gel analysis in particular and proteomics in
      general are discussed.

PMID- 11465507
TI  - Protein alkylation in the presence/absence of thiourea in proteome analysis: a
      matrix assisted laser desorption/ionization-time of flight-mass spectrometry
      investigation.
AB  - Although it is highly recommended that reduction and alkylation of free -SH
      groups in proteins should be performed prior to any electrophoretic step
      (including the first isoelectric focusing/immobilized pH gradient (IEF/IPG)
      dimension), it is here reported that one component of the sample solubilization
      cocktail adopted recently (namely thiourea) strongly quenches such alkylation
      process (as typically carried out with iodoacetamide, IAA). The present matrix
      assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF
      MS) analysis demonstrates that thiourea is an effective scavenger of IAA, since
      its sulfur atom reacts as efficiently as the ionized, free -SH group of Cys in
      proteins at alkaline pH values (pH 8.5-9.0). As a result of this reaction, free
      IAA is quickly depleted by thiourea, via the formation of an intermediate adduct,
      which is rapidly deamidated to form the cyclic compound thiazolinidone monoimine.
      This reaction strongly competes with the direct addition reaction of IAA onto the
      -SH group in proteins, resulting in poorly alkylated proteins. It is, therefore,
      recommended that, whenever possible and compatible with the type of sample,
      thiourea should be omitted from the solubilizing cocktail in proteome analysis.
      However, after proper sample reduction and alkylation, thiourea can be
      incorporated into the IEF/IPG gel, where it will have the beneficial effect of
      augmenting protein solubility at their pI values and scavenging the excess of
      free IAA.

PMID- 11465508
TI  - Quantitative and reproducible two-dimensional gel analysis using Phoretix 2D
      Full.
AB  - Quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is
      used to determine changes in individual protein levels in complex protein
      mixtures. To provide reliable data, the software used for 2-D gel image analysis
      must provide a linear response over a wide dynamic range of data output. Here, we
      show that Phoretix 2D Full analysis of 2-D gels stained with colloidal Coomassie
      Brilliant Blue G-250 can provide a linear measure of changes in protein quantity.
      We show using a complex mixture of Arabidopsis thaliana proteins, that this is
      true for essentially all focused proteins, in a data output range greater than
      three orders of magnitude. An analysis of the factors that affect errors in the
      results demonstrated that reproducibility of the data is significantly improved
      by user seeding, whereas it is reduced by use of the background subtraction
      algorithms.

PMID- 11465509
TI  - Changes in the brain protein levels following administration of kainic acid.
AB  - Kainic acid (KA), a potent neurotoxin and excitatory amino acid, leads to
      derangements and modulation of brain proteins. No global brain protein expression
      pattern induced by KA-treatment has been reported yet. We therefore studied the
      effect of systemic KA administration on the levels of brain proteins. Rats were
      injected placebo or KA intraperitoneally and brain was taken after one week. The
      mitochondrial and cytosolic fractions of the brain proteins were analyzed by
      proteomics technologies and the levels of selected proteins were quantified using
      specific software. Heat shock protein HSP 27 was exclusively detected in brains
      of animals treated with KA, whereas the glucose regulated protein GRP 78 was
      downregulated. The levels of neurofilaments and alpha-internexin were
      significantly decreased and a fragment of tubulin alpha-1 chain was manifold
      increased in KA-brains. The mitochondrial enzymes dihydrolipoamide dehydrogenase,
      ATP synthase beta chain and isocitrate dehydrogenase were reduced and pyruvate
      kinase M1 was increased following KA treatment. We conclude that the concomitant
      determination of the brain proteins indicates altered regulation of heat shock
      proteins, neuronal death, cytoskeletal disruption, and mitochondrial derangement
      by systemic KA administration. This report confirms and extends previous studies
      on the effect of KA on the expression of brain proteins and suggests that our
      analytical system can serve as a model for neurotoxicological, neurobiological,
      and neuropathological proteome studies.

PMID- 11465510
TI  - Decreased in vitro interaction between p53 and nuclear stress proteins in the p53
      deficient mouse.
AB  - In a previous study, the strength of the interaction between the nuclear stress
      proteins (sps) 25a, 70i, 72c, and 90 and the tumor suppressor protein p53 was
      determined by an in vitro fluorescence binding assay. The relative binding of the
      individual sps with p53, derived from the bone marrow of transgenic mice
      heterozygous at the p53 locus (p53+/-), was reduced compared to the interaction
      of sps and p53 derived from wild-type (p53+/+) mice. In order to determine if the
      genotype of the p53 donor or the genotype of the sp donor determined the binding
      efficiency, p53 expression was induced by retinoic acid and sp synthesis by
      bleomycin. P53 derived from either wild-type or heterozygous animals was cross
      reacted with nuclear sps obtained from either wild-type or heterozygous animals.
      Each of the sps, 25a, 70i, 72c, and 90, bound to wild-type p53 with a similar
      efficiency, irrespective of the genotype of the sp donor mouse (p53+/+ or p53+/
      ). In contrast, when the sp interaction with p53 obtained from the heterozygous
      mouse was measured, the relative value of the fluorescence complex was
      significantly reduced. The data suggest that the strength of the interaction
      between p53 and nuclear sps is related to the genotype of the p53 donor, and not
      to the genotype of the animals from which the sps are derived.

PMID- 11465511
TI  - A simple method for assigning multiple immunogens to their protein on a two
      dimensional blot and its application to asthma-causing allergens.
AB  - A "one-step" procedure, that not only removes the color and blocking proteins
      used in the colorimetric immunodetection step but also stains the proteins
      originally on the blot, is presented. Following immunostaining and recording of
      immunoreactive spots, the blot was allowed to air-dry overnight (or longer) at
      room temperature and then counterstained with a colloidal gold solution. This
      "air-drying" process apparently altered the affinity of the blocking proteins
      (and possibly other proteins added subsequently to the blotting step) towards the
      nitrocellulose membrane causing them to be removed by the acidic colloidal gold
      solution while the "blotted" proteins were being stained. The sensitivity of this
      counterstained blot was comparable to that of the blot without going through the
      immunodetection process. Since both immunodetection and protein staining were
      carried out on the same blot, this allowed easy identification of many
      immunoreactive spots to their corresponding proteins when the two profiles were
      superimposed. Using this procedure, we have detected 25 immunoreactive spots (or
      allergens) from the whole body extract of the German cockroach (Blattella
      germanica) that contribute to asthma and assigned them to their corresponding
      proteins on a two-dimensional (2-D) protein map. The apparent Mr and pI for each
      of the allergens were determined. We have also located one of the major cockroach
      allergens, Bla g 5 (glutathione S-transferase). Two-dimensional zymography
      revealed the presence of ten gelatinase-type proteolytic enzymes. Only one of the
      ten proteases comigrated with the immunoreactive proteins indicating that unlike
      other allergen-producing systems, most of the cockroach allergens do not possess
      protease activity.

PMID- 11465512
TI  - Two-dimensional electrophoretic analysis of rice proteins by polyethylene glycol
      fractionation for protein arrays.
AB  - Two-dimensional electrophoresis (2-DE) is known as the most effective as well as
      one of the simplest methods for separating proteins. However, a few hundred plant
      leaf proteins out of thousands visualized on a 2-DE gel can be identified by
      chemical analysis due to the presence of ribulose bisphosphate
      carboxylase/oxygenase (Rubisco) that limits protein loading. We describe the
      extraction and fractionation technique with polyethylene glycol (PEG) to analyze
      rice leaf proteins. Rice proteins were extracted with Mg/NP-40 extraction buffer.
      The Mg/Nonidet P-40 (NP-40) buffer extract was further fractionated with PEG into
      three fractions: 10% PEG and 10-20% PEG precipitants and the final supernatant
      fraction that was precipitated with acetone. Rubisco, the most abundant rice leaf
      protein, was enriched in the 20% PEG precipitant. This fractionation technique
      analyzed at least 2,600 well-separated protein spots and exhibited less than 1.2%
      of noticeable overlapping spots. An immunological approach was used to verify the
      efficiency whether PEG fractionation technique can detect or enrich signal
      transduction components such as Galpha, ADP ribosylation factor, small GTP
      binding protein and 14-3-3. The ADP ribosylation factor (ARF) and Galpha were
      only detected in the PEG supernatant fraction not in the total protein fraction.
      The small GTP binding protein (Rab 7) was identified in the 10% PEG fraction and
      only faintly in the total protein fraction. The 14-3-3 protein was detected in
      all fractions but was especially prevalent in the 20% PEG fraction.

PMID- 11465513
TI  - Cell immobilization induces changes in the protein response of Escherichia coli K
      12 to a cold shock.
AB  - We have compared the protein expression of gel-entrapped Escherichia coli cells
      submitted to a cold shock at 4 degrees C with those of exponential- and
      stationary-phase free-floating counterparts. Autoradiograms of two-dimensional
      gel electrophoresis patterns of proteins radiolabeled with L-[35S]methionine were
      compared using computing scanning densitometry. The levels of 203 proteins
      synthesized during the temperature shift were significantly and reproducibly
      higher than those corresponding to synthesis at 37 degrees C. A principal
      component analysis (PCA) was performed on the synthesis levels of these 203
      proteins in the different incubation conditions tested. This study showed that
      the protein response of immobilized cells after the cold shock was significantly
      different from those of exponential- and stationary-phase free-floating
      organisms. For instance, protein SSB was specifically overexpressed by shocked
      immobilized organisms. Such induction of specific molecular mechanisms in
      immobilized bacteria might explain the high resistance of sessile-like organisms
      to stresses.

PMID- 11465514
TI  - Fingerprinting of signal transduction pathways using a combination of anti
      phosphotyrosine immunoprecipitations and two-dimensional polyacrylamide gel
      electrophoresis.
AB  - Virtually all known cellular processes involve modulation of cellular signaling
      pathways via changes in protein phosphorylation. With genomics efforts more than
      doubling the number of proteins available for analysis, a major challenge will be
      to identify unknown phosphoproteins as they exist in the normal or diseased
      intracellular environment. Recent advances in proteomic technology have made it
      possible to examine changes in protein expression with much greater resolution
      than was previously possible. In this report, we describe a rapid and
      reproducible method for identifying phosphoproteins upregulated in response to
      activation of cell surface receptors. Phosphotyrosine-containing proteins were
      immunoprecipitated from IFNalpha- or IL2-treated primary human lymphocyte
      extracts using a novel anti-phosphotyrosine immunoprecipitation technique. This
      technique takes advantage of differing antibody affinities for epitopes on native
      versus denatured proteins. Following separation from the immunopellets,
      phosphoproteins are resolved by two-dimensional polyacrylamide gel
      electrophoresis. With this method, we identified known proteins phosphorylated in
      response to IL2 or IFNalpha using both silver staining and Western blotting for
      protein detection/identification. The silver-stained immunoprecipitation profile
      serves as a fingerprint for phosphorylation events that occur in response to
      cytokine treatment. By merging these techniques with mass spectrometric
      microsequencing, new capabilities are achieved. It will then be possible to
      identify novel signaling proteins that are activated in response to a variety of
      stimuli, including receptor activation, disease progression, etc.

PMID- 11465515
TI  - Natural estrogen as an antidepressant for women.
AB  - Recent well-controlled studies suggest that estrogen has antidepressant actions
      in perimenopausal women. Estrogen may also have antidepressant actions in
      postpartum women and across the life cycle for women who are resistant to
      treatment with various antidepressants. The question, however, of which depressed
      women to treat with antidepressants, which with estrogen, and which with both
      remains unanswered.

PMID- 11465516
TI  - Testosterone replacement therapy for hypogonadal men with major depressive
      disorder: a randomized, placebo-controlled clinical trial.
AB  - BACKGROUND: Symptoms of male hypogonadism include low libido, fatigue, and
      dysphoria and are alleviated with testosterone replacement. The prevalence of
      major depressive disorder (MDD) in hypogonadal men is not known, nor is the
      antidepressant efficacy of testosterone replacement in depressed, hypogonadal
      men. METHOD: A 6-week double-blind, placebo-controlled clinical trial was
      conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as
      total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to
      receive weekly 1-mL intramuscular injections of either testosterone enanthate,
      200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item
      Hamilton Rating Scale for Depression (HAM-D). RESULTS: Thirty patients were
      randomly assigned to an intervention; 13 received testosterone, and 17 received
      placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/
      50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received
      testosterone achieved normalization of their testosterone levels. The HAM-D
      scores decreased in both testosterone and placebo groups, and there were no
      significant between-group differences: reduction in group mean HAM-D score from
      baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in
      those who received placebo. Response rate, defined as a 50% or greater reduction
      in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2%
      (7/17) for patients who received placebo. Patients receiving testosterone had a
      marginal but statistically significant improvement in sexual function (p = .02).
      CONCLUSION: In this clinical trial with depressed, hypogonadal men,
      antidepressant effects of testosterone replacement could not be differentiated
      from those of placebo.

PMID- 11465517
TI  - Efficacy and safety of mirtazapine in major depressive disorder patients after
      SSRI treatment failure: an open-label trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of mirtazapine in depressed
      outpatients who have shown nonresponse or intolerance to selective serotonin
      reuptake inhibitor (SSRI) therapy. METHOD: In this open-label, 8-week study, the
      efficacy and safety of mirtazapine among 103 outpatients with DSM-IV major
      depressive disorder who had failed previous therapy with an SSRI (fluoxetine,
      paroxetine, or sertraline) were evaluated. The primary efficacy measure was the
      17-item Hamilton Rating Scale for Depression (HAM-D-17), and safety assessments
      included reported adverse events, routine laboratory assessments, physical
      examinations, and assessments of vital signs. A 4-day washout period followed by
      mirtazapine treatment was compared with an immediate switch from the SSRI to
      mirtazapine. RESULTS: Based on mean HAM-D-17 scores at endpoint and response
      rates of 48% based on the criterion of > or = 50% reduction in HAM-D-17 score,
      mirtazapine was found to be an effective treatment for a substantial proportion
      of patients for whom an SSRI was ineffective and/or poorly tolerated. Mirtazapine
      was well tolerated, with sedation and appetite increase/weight gain the most
      commonly reported adverse events. In addition, no difference in efficacy, safety,
      or tolerability was observed for patients undergoing an immediate switch from an
      SSRI (after having been tapered to the minimal effective dose) to mirtazapine,
      compared with those undergoing the imposition of a 4-day drug-free washout.
      CONCLUSION: These results suggest that an immediate switch to mirtazapine may be
      a valid therapeutic option among patients who cannot tolerate or do not respond
      to SSRIs.

PMID- 11465518
TI  - The development of study exit criteria for evaluating antimanic compounds.
AB  - BACKGROUND: There is increasing interest on the part of investigators and the
      public at large in finding ways to study and improve treatments for the seriously
      mentally ill without exposing such individuals to unnecessary risks. One group of
      particular interest in this regard are patients suffering from acute mania. We
      set out to define "exit" criteria or novel clinical endpoints that might help to
      assess the efficacy of antimanic compounds. We sought a method that would be
      safer, more economical, and less sensitive to nonspecific factors in the clinical
      environment while still allowing unambiguous assessment of efficacy. METHOD: From
      a pool of subjects being screened for or already participating in intervention
      studies, we retrospectively identified 76 admissions of patients with a manic or
      mixed episode according to DSM-IV. We fit a mixed-effects regression model to all
      available data obtained using the Bech-Rafaelsen Mania Scale from admission to
      day 28 of treatment. Using the estimated model coefficients, we obtained
      empirical Bayes (EB) estimates of each subject's trend coefficients based on (1)
      all available data and (2) data through day 11 of treatment for mania. RESULTS:
      We found a high correlation (r = .67) between EB estimates of final response at
      day 28 and actual day 28 scores on the Bech-Rafaelsen scale based on scores
      through day 11. When subjects were categorized as full, partial, or nonresponders
      according to their final Bech-Rafaelsen score, we were able to show that only 2
      of the 23 predicted nonresponders became full responders, 27 of the 31 predicted
      full responders became full responders, and 16 of the 22 predicted partial
      responders became partial or full responders. CONCLUSION: We conclude on the
      basis of this chart review study that it should be possible to define exit
      criteria for trials assessing the efficacy of antimanic compounds on the basis of
      relatively short duration exposure to experimental treatment.

PMID- 11465519
TI  - A preliminary survey of rhinotillexomania in an adolescent sample.
AB  - BACKGROUND: Rhinotillexomania is a recent term coined to describe compulsive nose
      picking. There is little world literature on nose-picking behavior in the general
      population. METHOD: We studied nose-picking behavior in a sample of 200
      adolescents from 4 urban schools. RESULTS: Almost the entire sample admitted to
      nose picking, with a median frequency of 4 times per day; the frequency was > 20
      times per day in 7.6% of the sample. Nearly 17% of subjects considered that they
      had a serious nose-picking problem. Other somatic habits such as nail biting,
      scratching in a specific spot, or pulling out of hair were also common; 3 or more
      such behaviors were simultaneously present in 14.2% of the sample, only in males.
      Occasional nose bleeds complicating nose picking occurred in 25% of subjects.
      Several interesting findings in specific categories of nose pickers were
      identified. CONCLUSION: Nose picking is common in adolescents. It is often
      associated with other habitual behaviors. Nose picking may merit closer
      epidemiologic and nosologic scrutiny.

PMID- 11465520
TI  - Anxiety disorders following miscarriage.
AB  - BACKGROUND: Several previous studies have established that miscarriage is a risk
      factor for depressive symptoms and disorder. By contrast, research on miscarriage
      as a possible risk factor for anxiety symptoms is inconclusive, and for anxiety
      disorders, sparse and uninformative. The current study examines the incidence of
      and relative risk for 3 DSM-III anxiety disorders (obsessive-compulsive disorder
      [OCD], panic disorder, and phobic disorders) within the 6 months following
      miscarriage. Adequate diagnostic data on other anxiety disorders were not
      available. METHOD: Using a cohort design, we tested whether women who miscarry
      are at increased risk for a first or recurrent episode of an anxiety disorder in
      the 6 months following loss. The miscarriage cohort consisted of women attending
      a medical center for spontaneous abortion (N = 229); the comparison group was a
      population-based cohort of women drawn from the community (N = 230). RESULTS:
      Among miscarrying women, 3.5% experienced a recurrent episode of OCD, compared
      with 0.4% of community women (relative risk [RR] = 8.0; 95% confidence interval
      [CI] = 1.0 to 63.7). The relative risk for noncomorbid panic disorder was
      substantial (RR = 3.6), albeit not statistically significant (95% CI = 0.8 to
      17.2). There was no strong evidence for increased risk for phobic disorders or
      agoraphobia, combined or considered separately, in the 6 months following loss.
      Relative risk for all 3 disorders combined was 1.5 (95% CI = 0.9 to 2.3).
      CONCLUSION: In this first miscarriage cohort study using a concurrent frequency
      matched comparison group, miscarriage was a substantial risk factor for an
      initial or recurrent episode of OCD. Given statistical power limitations of this
      investigation, the current findings do not preclude a possible contribution of
      miscarriage to risk for other anxiety disorders.

PMID- 11465521
TI  - Texas Medication Algorithm Project: development and feasibility testing of a
      treatment algorithm for patients with bipolar disorder.
AB  - BACKGROUND: Use of treatment guidelines for treatment of major psychiatric
      illnesses has increased in recent years. The Texas Medication Algorithm Project
      (TMAP) was developed to study the feasibility and process of developing and
      implementing guidelines for bipolar disorder, major depressive disorder, and
      schizophrenia in the public mental health system of Texas. This article describes
      the consensus process used to develop the first set of TMAP algorithms for the
      Bipolar Disorder Module (Phase 1) and the trial testing the feasibility of their
      implementation in inpatient and outpatient psychiatric settings across Texas
      (Phase 2). METHOD: The feasibility trial answered core questions regarding
      implementation of treatment guidelines for bipolar disorder. A total of 69
      patients were treated with the original algorithms for bipolar disorder developed
      in Phase 1 of TMAP. RESULTS: Results support that physicians accepted the
      guidelines, followed recommendations to see patients at certain intervals, and
      utilized sequenced treatment steps differentially over the course of treatment.
      While improvements in clinical symptoms (24-item Brief Psychiatric Rating Scale)
      were observed over the course of enrollment in the trial, these conclusions are
      limited by the fact that physician volunteers were utilized for both treatment
      and ratings. and there was no control group. CONCLUSION: Results from Phases 1
      and 2 indicate that it is possible to develop and implement a treatment guideline
      for patients with a history of mania in public mental health clinics in Texas.
      TMAP Phase 3, a recently completed larger and controlled trial assessing the
      clinical and economic impact of treatment guidelines and patient and family
      education in the public mental health system of Texas, improves upon this
      methodology.

PMID- 11465522
TI  - Patients with severe depression may benefit from buspirone augmentation of
      selective serotonin reuptake inhibitors: results from a placebo-controlled,
      randomized, double-blind, placebo wash-in study.
AB  - BACKGROUND: Although case reports and open studies have reported augmentation
      with buspirone to be beneficial in the treatment of depression refractory to
      treatment with a selective serotonin reuptake inhibitor (SSRI), a recently
      published randomized, placebo-controlled, double-blind study failed to show
      superiority of buspirone over placebo in this respect. METHOD: One hundred two
      outpatients who fulfilled DSM-IV criteria for a major depressive episode and who
      had failed to respond to a minimum of 6 weeks of treatment with either fluoxetine
      or citalopram were included in this double-blind, randomized, placebo-controlled
      study. After a single-blind placebo wash-in period of 2 weeks while continuing
      their SSRI, the patients were randomly assigned to adjunctive treatment with
      either buspirone, 10 to 30 mg b.i.d., or placebo for 6 weeks. Patients were
      assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), the
      Clinical Global Impressions scale (CGI), and visual analogue scales. RESULTS:
      After the first week of double-blind treatment, there was a significantly greater
      reduction in MADRS score (p = .034) in the buspirone group as compared with
      placebo. At endpoint, there was no significant difference between treatment
      groups as a whole, although patients with initially high MADRS scores (> 30)
      showed a significantly greater reduction in MADRS score (p = .026) in the
      buspirone group as compared with placebo. CONCLUSION: Patients with severe
      depressive symptoms may benefit from augmentation with buspirone. It cannot be
      excluded that augmentation with buspirone may speed up the antidepressive
      response of patients refractory to treatment with fluoxetine or citalopram.

PMID- 11465523
TI  - Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind,
      polysomnographic study.
AB  - BACKGROUND: Over recent years, the use of antidepressants for the symptomatic
      treatment of insomnia has grown substantially, but controlled studies are still
      lacking. Our study is the first investigation to prove objective efficacy and
      tolerability of low doses of a sedating antidepressant in a randomized, double
      blind, and placebo-controlled manner in patients with primary insomnia. METHOD:
      Forty-seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean
      +/- SD duration of complaints = 11.2+/-9.7 years) received either 25-50 mg of the
      tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of
      placebo withdrawal. Sleep was measured by polysomnography at baseline and the
      first night of application, at 4 weeks of treatment and the first to third night
      of withdrawal, and after 2 weeks of withdrawal. RESULTS: In the doxepin-treated
      patients who completed the study (N = 20, 47.6+/-11.3), medication significantly
      increased sleep efficiency after acute (night 1, p < or = .001) and subchronic
      (night 28, p < or = .05) intake compared with the patients who received placebo
      (N = 20, 47.4+/-16.8 years of age). Latency to sleep onset was not affected since
      the patients had normal baseline sleep latencies. Investigators found doxepin to
      cause significantly (p < or = .05) better global improvement at the first day of
      treatment. Patients rated sleep quality (p < or = .001) and working ability (p <
      or = .005) to be significantly improved by doxepin during the whole treatment
      period. Overall rebound in sleep parameters was not observed, but patients with
      severe rebound insomnia were significantly more frequent in the doxepin group
      (night 29, p < .01, night 30, p < or = .01; night 31, p < or = .05). No
      significant group differences in side effects were found, but 2 doxepin-treated
      patients dropped out of the study due to specific side effects (increased liver
      enzymes, leukopenia, and thrombopenia). CONCLUSION: The results support the
      effectiveness of low doses of doxepin to improve sleep and working ability in
      chronic primary insomniacs, although subjective effects were light to moderate,
      and in some patients, rebound insomnia and specific side effects have to be
      considered.

PMID- 11465524
TI  - Antimanic efficacy of topiramate in 11 patients in an open trial with an on-off
      on design.
AB  - BACKGROUND: A series of open studies suggests that topiramate has efficacy in
      bipolar disorder. To further investigate the potential value of topiramate as an
      antimanic agent, we conducted an open trial in 11 manic patients. METHOD: Eleven
      patients with bipolar I disorder with an acute manic episode (DSM-IV) were
      treated with a mood stabilizer and/or antipsychotics in sufficient and fixed
      doses. All had a Young Mania Rating Scale (YMRS) score of at least 24 (mean +/-
      SD = 33.5+/-8.1). Topiramate was added after stable plasma levels of concomitant
      mood stabilizers had been reached and was titrated within 1 week to a final dose
      in the range of 25 to 200 mg/day, depending on clinical efficacy and
      tolerability. Topiramate was discontinued after 10 days, while concomitant
      medication remained unchanged. After 5 days, topiramate was reintroduced at
      similar or increased dosages for another 7 days. Patients were assessed with the
      YMRS; the Clinical Global Impressions scale version for bipolar patients; and the
      21-item Hamilton Rating Scale for Depression. RESULTS: Seven of the 11 patients
      initially showed a good antimanic response with > 50% reduction in YMRS score.
      One patient showed psychotic features following rapid increase in topiramate
      dosage and dropped out on day 10. After discontinuation of topiramate, 7 of the
      remaining 10 patients worsened (increase of > or = 25% in YMRS score), 2 remained
      stable, and 1 discontinued follow-up after good recovery. After reintroducing
      topiramate, all patients improved again within a week, with 8 of 9 meeting the
      responder criterion of > or = 50% YMRS score reduction when comparing baseline
      values with those of day 22. With the exception of the patient who developed
      psychosis, topiramate was well tolerated. Concomitant medication did not
      interfere with plasma levels of drug, except for carbamazepine level in 1
      patient. CONCLUSION: The antimanic response among patients in this study appears
      reproducibly linked to the addition of topiramate.

PMID- 11465525
TI  - A placebo-controlled, crossover trial of granisetron in SRI-induced sexual
      dysfunction.
AB  - BACKGROUND: Sexual side effects are commonly associated with serotonin reuptake
      inhibitor (SRI) therapy. The mechanism underlying SRI-induced sexual dysfunction
      has been hypothesized to be mediated by direct serotonergic effects. Evidence
      from open-label reports suggests that cyproheptadine, nefazodone, mirtazapine,
      and mianserin, which block one or more serotonin receptors, may reverse sexual
      side effects. The current study was a prospective, randomized, crossover trial
      comparing granisetron, a serotonin-3 antagonist, with placebo in outpatients who
      developed sexual dysfunction during SRI treatment. METHOD: Thirty-one outpatients
      who were currently experiencing sexual dysfunction associated with SRIs were
      randomly assigned to double-blind treatment with granisetron (1-1.5 mg) or
      placebo for use 1 to 2 hours prior to sexual activity. Patients rated sexual
      symptoms after each trial using the Sexual Side Effect Scale (SSES). After 4
      trials of the medication, patients crossed over to the other treatment for 4 more
      trials. RESULTS: Twenty patients received at least 1 dose of placebo and
      granisetron. Analysis by repeated-measures analysis of variance showed no
      significant effects of granisetron relative to placebo. Significant improvement
      between baseline and treatment-phase SSES scores was observed for both
      granisetron (p = .0004) and placebo (p = .0081). The study medication was
      generally well tolerated. CONCLUSION: The results of this study do not support
      the efficacy of granisetron (1-2 mg) in the treatment of SRI-associated sexual
      side effects. A significant placebo response may be associated with the treatment
      of SRI-induced sexual dysfunction.

PMID- 11465526
TI  - Gabapentin for the treatment of patients with somatization disorder.

PMID- 11465527
TI  - Acronyms for substance use disorders.

PMID- 11465528
TI  - Topiramate abuse in a bipolar patient with an eating disorder.

PMID- 11465529
TI  - Seizure during combination of trimipramine and bupropion.

PMID- 11465530
TI  - Clozapine in the treatment of hypomania with neurosyphilis.

PMID- 11465531
TI  - Internet-observed suicide attempts.

PMID- 11465532
TI  - Changing paradigms: depressed patients as treatment partners.

PMID- 11465533
TI  - Clozapine in the treatment of aggression in an adolescent with autistic disorder.

PMID- 11465534
TI  - Determinants of overweight and obesity in patients with bipolar disorder.
AB  - OBJECTIVE: To examine lifestyle-related determinants of the excess adiposity
      observed in patients with bipolar disorder. METHOD: Eighty-nine male and female
      patients with DSM-IV bipolar disorder who were attending a specialist bipolar
      clinic or another psychiatric outpatient clinic (19% with body mass index [BMI] >
      or = 30) and 445 age- and sex-matched reference subjects (12% with BMI > or = 30)
      participated in a cross-sectional study of nutrient intake and physical activity.
      Main outcome measures included macronutrient intakes (assessed with 24-hour
      recall), percentage of energy derived from various food sources, and physical
      activity levels (assessed with the Life in New Zealand Questionnaire). RESULTS:
      Mean total energy intake was higher in female patients than in reference
      subjects: 8468 kJ compared with 6980 kJ (95% confidence interval [CI] = 583 to
      2392 kJ). Total daily sucrose and percentage of energy from carbohydrate were
      higher in patients than in reference subjects; for women, 73 g and 49% (95% CI =
      20 to 56 g, 3% to 10) and for men, 89 g and 47% (95% CI = 15 to 59 g, 3% to 9%).
      Total fluid intake and intake of sweetened drinks were higher in patients than in
      reference subjects (ratio of geometric means: women, 1.2 and 2.3, respectively
      [95% CI = 1.1 to 1.4, 1.9 to 2.8]; men, 1.1 and 2.1, respectively [95% CI = 1.0
      to 1.23, 1.8 to 2.41). Patients reported fewer episodes of low- to moderate
      intensity and high-intensity physical activity as compared with reference
      subjects (p < or = .05). CONCLUSION: This study confirms that drug-induced
      changes in food preference can lead to an excessive energy intake largely as a
      result of a high intake of sucrose. Dietary advice regarding the use of energy
      rich beverages along with encouragement to increase levels of physical activity
      may help prevent weight gain in bipolar patients. The findings also have some
      bearing on dietary advice aimed at avoiding overweight and obesity in the general
      population.

PMID- 11465535
TI  - Physiological roles for K+ channels and gap junctions in urogenital smooth
      muscle: implications for improved understanding of urogenital function, disease
      and therapy.
AB  - Smooth muscle cells constitute a heterogeneous collection of effector cells that,
      by virtue of both their constituency in blood vessels and presence as primary
      parenchymal cells in diverse tissues, affect the function of all organs. Thus,
      perhaps it is not surprising that alterations in, and/or dysfunction of, smooth
      muscle cells are quite common, and responsible, at least in part, for the
      morbidity and mortality associated with a very wide range of human diseases.
      These facts point to the necessity for improved understanding of the mechanism(s)
      governing the control of myocyte contractility (i.e., tone). Such understanding
      has been rapidly forthcoming in recent years, and has indicated that in many
      smooth muscle cell types intercellular communication through gap junctions acts
      in concert with nonjunctional (K+) ion channels to make important contributions
      to the control of myocyte tone and tissue homeostasis in physiologically diverse
      organs. Intercellular communication through connexin43-derived gap junction
      channels and K+ flux through the KCa and KATP channel subtypes, in particular,
      appear to play prominent roles in this process. The goal of this report,
      therefore, is to review the data concerning junctional and nonjunctional ion
      channels on the detrusor myocytes of the urinary bladder, as well as on the
      specialized vascular myocytes of the corpus cavernosum. The choice of an
      excitable (i.e., bladder detrusor myocytes) and nonexcitable (i.e., corporal
      smooth muscle) smooth muscle cell type ensures that the discussion will at least
      encompass consideration of a large portion of the spectrum of physiological
      possibilities for the participation of junctional and nonjunctional ion channels
      in the initiation, maintenance and modulation of smooth muscle tone. A central
      thesis of this communication is that detailed knowledge of the myocyte- and
      tissue-specific properties of K+ channels and gap junctions will likely lead to
      the improved understanding and treatment of human smooth muscle
      diseases/disorders.

PMID- 11465536
TI  - New developments in anti-platelet therapies: potential use of CD39/vascular ATP
      diphosphohydrolase in thrombotic disorders.

PMID- 11465537
TI  - Chemokine receptors as anti-retroviral targets.
AB  - The discovery that chemokine receptors act as cofactors indispensable for HIV
      entry into target cells identified new targets for anti-retroviral therapy.
      However, much remains to be learned about the nature of their physiological role
      in the organism, as well as the molecular details of viral entry. The multitude
      of different receptors permitting HIV entry in vitro and their respective roles
      in vivo for entry, as well as their implication in distinct pathogenic events
      have added further complexity to this field of research. This review summarizes
      knowledge on HIV-coreceptors, their role under normal physiological conditions as
      well as in HIV pathogenesis and its implications on the development of concepts
      for the use of coreceptor targeting therapeutic approaches. An overview over
      antiviral ligands of chemokine receptors reported so far, as well as alternative
      strategies of antiviral interventions involving chemokine receptors is given.

PMID- 11465538
TI  - Receptor tyrosine kinases as therapeutic targets: the model of the MET oncogene.
AB  - Control of cell growth and differentiation occurs via extracellular signals known
      as growth factors. Growth factors are high affinity ligands for transmembrane
      receptors belonging to the family of receptor tyrosine kinases (RTKs). A number
      of genetic evidences have implicated RTKs in human diseases including
      developmental disorders and cancer. For instance, germline missense mutations
      involving the Ret receptor are found in patients affected by multiple endocrine
      neoplasia types 2A and 2B (MEN2A and MEN2B) or familial medullary thyroid
      carcinomas. Somatic mutations in the Kit receptor are found in mastocytomas and
      in gastrointestinal tumors. Germline and sporadic mutations of the Met receptor
      have been described in kidney and hepatocellular carcinomas. Overexpression of
      the HER-2/neu receptor in breast cancer has been associated with tumor
      progression. The enzymatic activity of RTKs is strictly regulated and is usually
      inhibited under basal conditions. Receptor activation triggers a biochemical
      signalling cascade inside the cytoplasm, named signal transduction, which is
      subverted during the malignant transformation of cells. Signal transduction by
      RTKs is a multistep process which includes: (i) Ligand binding and receptor
      dimerization, (ii) receptor phosphorylation on tyrosine residues; (iii)
      recruitment to the receptor and activation of cytoplasmic signaling molecules
      that transmit signals to the nucleus. Each of the steps involved in this process
      can potentially be targeted to block the aberrant properties of tyrosine kinase
      receptors. By using the MET oncogene as a model this review focuses on the
      strategies that can be applied to therapeutically target RTKs.

PMID- 11465539
TI  - Signal transduction pathways and transcriptional mechanisms as targets for
      prevention of emergence of multidrug resistance in human cancer cells.
AB  - Pleiotropic resistance of tumor cells to treatment remains one of the major
      obstacles for successful cure of cancer patients. Tumor cells may acquire
      multidrug resistance (MDR) in the course of exposure to various compounds that
      are used in modern anticancer therapy, including cytotoxic drugs and
      differentiating agents. Therefore, the recurrence of the disease after the
      initial treatment may be associated with establishment of secondary MDR in the
      residual tumor. This phenotype is frequently mediated by P-glycoprotein, an ATP
      dependent transmembrane pump capable of effluxing numerous compounds out of the
      cell. In humans, P-glycoprotein is encoded by the MDR1 gene. Rapid increase of
      the steady-state level of the MDR1 mRNA in response to stress stimuli is the
      mechanism of acquisition of P-glycoprotein-mediated MDR in cancer cells. Thus, up
      regulation of the MDR1 gene is regarded as part of cellular stress response. This
      review shows that block of mechanisms that regulate the MDR1 overexpression can
      prevent the emergence of MDR in tumor cells that expressed null-to-low levels of
      MDR1 mRNA or P-glycoprotein prior to treatment. In particular, the MDR1
      activation can be abrogated by targeting cytoplasmic pathways of signal
      transduction as well as by interfering with transcriptional up-regulation.

PMID- 11465540
TI  - Discovery and design of selective cyclooxygenase-2 inhibitors as non-ulcerogenic,
      anti-inflammatory drugs with potential utility as anti-cancer agents.
AB  - The recent marketing of two selective cyclooxygenase-2 (COX-2) inhibitors,
      celecoxib and rofecoxib is remarkable considering that COX-2 was only discovered
      eight years ago as a growth factor- and cytokine-inducible gene. Concomitant with
      these pharmaceutical successes is the advances in our understanding of the
      molecular and structural basis for selective COX-2 inhibition. This review
      provides a perspective on the ongoing structure-activity relationship (SAR)
      efforts in the search of COX-2-specific inhibitors with particular reference to
      their structural basis for isozyme-specific inhibition. In addition to the
      existing inhibitor classes, this review will also highlight many novel structural
      classes which have recently emerged due to a better understanding of the active
      site differences between the two isozymes with a special emphasis on the
      modification of the well-established non-steroidal anti-inflammatory drug (NSAID)
      scaffold. In addition to its role in inflammation, recent studies suggest that
      COX-2-derived prostaglandins may play a pivotal part in the maintenance of tumor
      viability, growth, and metastasis. In this review, we summarize the NSAID
      epidemiological evidence, studies demonstrating overexpression of COX-2 in
      multiple human tumors and pharmacological evidence in animal models, which
      indicate that COX-2 inhibitors could be used in the prevention or treatment of a
      broader range of disease.

PMID- 11465541
TI  - Frequency and distribution in three ethnic populations of single nucleotide
      polymorphisms in the MICA gene.
AB  - The Homo sapiens major histocompatibility complex (MHC) class 1 chain related
      gene A (MICA) was scanned for novel single nucleotide polymorphisms (SNPs) using
      a panel of DNA samples from African-, Japanese- and Mexican-Americans.
      Overlapping primer-pairs were used to amplify products in the size range of 300
      to 400 bp that were sequenced and scanned for SNPs using Phred, Phrap, Polyphred
      and Consed sequence analysis programs. A total of 16 SNPs were detected, six of
      which represent new variant nucleotides in the Homo sapiens MICA gene. Three of
      the variants also represent amino acid changes in the MICA protein. Differences
      among the three ethnic panels in the frequency of the variant nucleotides
      observed were inconsistent, but significant for seven of the SNPs detected.
      Though a small sample size, this study represents the first multi-population
      based analysis of the frequency and distribution of SNPs in the MICA gene, a
      locus that may be essential in the antigenic recognition by gammadelta T cells.

PMID- 11465542
TI  - Common polymorphisms and somatic mutations in human base excision repair genes in
      ovarian and endometrial cancers.
AB  - The purpose of this study was to determine whether the human APEX and OGG1 genes,
      encoding proteins important in base excision repair (BER) of DNA, contain
      nucleotide sequence polymorphisms or are mutated somatically in tumors from women
      diagnosed with ovarian or endometrial cancer. Based upon the analysis of germline
      DNA from 83 individuals, 63 with ovarian cancer and 20 with endometrial cancer,
      we found two missense polymorphisms in APEX (Q51H and D 148E) and two missense
      (A3P and S326C) and one intronic (Exon 5-15 bp) polymorphism in OGG1. The
      frequencies of the various alleles (in the ovarian and endometrial cancer
      patients combined) were 4.8% for 51-His and 56.2% for 148-Glu in APEX, and 1.0%
      for 3-Pro and 20.0% for 326-Cys in OGG1. Somatic mutations in APEX (P112L, W188X
      and R237C) were identified in three of 20 endometrial tumors, but no mutations
      were identified in APEX in 43 ovarian tumors, or in OGG1 at either tumor site.
      Given the crucial role of the APEX and OGG1 proteins in BER of oxidative DNA
      damage, the identified polymorphisms are good candidates for genetic
      epidemiologic studies of cancer susceptibility, while the finding that three of
      20 (15%) endometrial tumors have somatic mutations in APEX suggests that
      inactivation of the BER pathway is important for the development of endometrial
      cancer in at least a subset of cases.

PMID- 11465543
TI  - Identification of genetic variants in the human thromboxane synthase gene
      (CYP5A1).
AB  - Thromboxane synthase (CYP5A1) catalyzes the conversion of prostaglandin H2 to
      thromboxane A2, a potent mediator of platelet aggregation, vasoconstriction and
      bronchoconstriction. It has been implicated in the patho-physiological process of
      a variety of diseases, such as atherosclerosis, myocardial infarction, stroke and
      asthma. On the basis of the hypothesis that variations of the CYP5A1 gene may
      play an important role in human diseases, we performed a screening for variations
      in the human CYP5A1 gene sequence. We examined genomic DNA from 200 individuals,
      for mutations in the promoter region, the protein encoding sequences and the 3'
      untranslated region of the CYP5A1. Eleven polymorphisms have been identified in
      the CYP5A1 gene including eight missense mutations R61H, D161E, N246S, L357V,
      Q417E, E450K, T451N and R466Q. This is the first report of genetic variants in
      the human CYP5A1 altering the protein sequence. The effect of these variants on
      the metabolic activity of CYP5A1 remains to be further evaluated.

PMID- 11465544
TI  - An improved real time PCR method for simultaneous detection of C282Y and H63D
      mutations in the HFE gene associated with hereditary hemochromatosis.
AB  - HFE-linked hereditary hemochromatosis (HH) is one of the most common inherited
      diseases among individuals of Northern European ancestry. Two sites of point
      mutations in the HFE gene--C282Y and H63D--are associated with greater than 90%
      of HH cases. We have developed a sensitive real time PCR (TaqMan) 5'-nuclease
      assay for single nucleotide polymorphism (SNP) detection using novel DNA
      chemistry, and successfully applied this method to detect these mutations.
      Fluorogenic PCR probes, chemically modified with a minor groove binding agent to
      increase duplex stability, were used in single and multiplex probe closed tube
      formats. The probes were tested in two commercially available thermocycling
      fluorimeters (the Light Cycler and the ABI Prism 7700). Comparison of the results
      obtained from the analysis of 43 samples showed no discrepancies between our 5'
      nuclease assay and the restriction length polymorphism analysis, which is
      routinely used in hospitals. The reported real time PCR technology is ideal for
      the clinical setting as it is sensitive, eliminates the labor and supply costs of
      post-PCR steps, reduces the risk of crossover contamination, minimizes sources of
      error, and can be fully automated.

PMID- 11465545
TI  - Three novel mutations causing a truncated protein within the RP2 gene in Italian
      families with X-linked retinitis pigmentosa.
AB  - X-linked retinitis pigmentosa (XLRP) results from mutations in a number of loci,
      including RP2 at Xp11.3, and RP3 at Xp21.1. RP2 and RP3 genes have been
      identified by positional cloning. RP2 mutations are found in about 10% of XLRP
      patients. We performed a mutational screening of RP2 gene inpatients belonging to
      seven unrelated families in linkage with the RP2 locus. SSCP analysis detected
      three conformation variants, within exon 2 and 3. Direct sequencing of exon 2,
      disclosed a G-->A transition at nucleotide 449 (W150X), and a G-->T transversion
      in position 547 (E183X). Sequence analysis of exon 3 variant revealed an
      insertion (853/854insG), leading to a frameshift. In this patient, we detected an
      additional sequence alteration (A-->G at nucleotide 848, E283G). Each mutation
      was co-segregating with the disease in the affected family members available for
      the study. These mutations are expected to introduce a stop codon within the RP2
      coding sequence probably resulting in a truncated or unstable protein.

PMID- 11465546
TI  - Automated anesthesia: fact or fantasy?

PMID- 11465547
TI  - Pulmonary vasoconstriction during regional nitric oxide inhalation: evidence of a
      blood-borne regulator of nitric oxide synthase activity.
AB  - BACKGROUND: Inhaled nitric oxide (INO) is thought to cause selective pulmonary
      vasodilation of ventilated areas. The authors previously showed that INO to a
      hyperoxic lung increases the perfusion to this lung by redistribution of blood
      flow, but only if the opposite lung is hypoxic, indicating a more complex
      mechanism of action for NO. The authors hypothesized that regional hypoxia
      increases NO production and that INO to hyperoxic lung regions (HL) can inhibit
      this production by distant effect. METHODS: Nitric oxide concentration was
      measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and
      regional pulmonary blood flow in anesthetized pigs with regional left lower lobar
      (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO
      to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and
      without INO. RESULTS: Left lower lobar hypoxia increased exhaled NO from the LLL
      (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P
      < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic
      lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P < 0.05). INO to HL
      decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(
      1) x min(-1) (P < 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P < 0.05). When open
      chest pigs with LLL hypoxia received blood from closed-chest pigs with INO,
      NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+
      dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol
      x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)%
      (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung
      regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow
      away from hypoxic to hyperoxic lung regions. CONCLUSIONS: Inhaled nitric oxide
      downregulates endogenous NO production in other, predominantly hypoxic, lung
      regions. This distant effect is blood-mediated and causes vasoconstriction in
      lung regions that do not receive INO.

PMID- 11465548
TI  - Local anesthetic effects on priming and activation of human neutrophils.
AB  - BACKGROUND: Local anesthetics (LAs) have been shown to inhibit human
      polymorphonuclear neutrophil (hPMN) functions in vitro, but mechanisms are poorly
      understood. In this study the authors determined how LAs affect superoxide anion
      production of hPMNs primed with platelet-activating factor (PAF). The authors
      studied which pharmacologic properties of LAs are important for this action and
      assessed the LA site of action within the PAF signaling pathway. METHODS:
      Metabolic activity of primed and/or activated hPMNs were measured using the
      cytochrome-c assay. hPMNs were incubated with several LAs for 1 h to assess
      interference with PAF signaling. Using protein kinase C (PKC) inhibitors, the PKC
      activator phorbol myristate acetate (PMA), and the phospholipase C (PLC)
      antagonist U-73122, we studied involvement of PKC and PLC in the priming process.
      Pertussis toxin (PTX) was used to characterize the G proteins mediating this
      pathway. Combined administration of lidocaine with PMA or PTX was used to
      determine the LA site of action within the priming pathway. RESULTS: Platelet
      activating factor effectively primed hPMNs. Ester LAs (tetracaine and benzocaine)
      exerted the most profound inhibitory effect on PAF-primed hPMNs, whereas
      inhibitory potency of amide LAs increased with decreased charged fraction. The
      major PAF-induced priming pathway is PLC- and PKC-dependent and mainly Gq
      mediated. The main target site for LA in this pathway is located upstream of PKC.
      CONCLUSIONS: Local anesthetics in clinically relevant concentrations inhibit
      superoxide anion production of PAF-primed hPMNs. Effects on priming by these
      compounds might explain, at least in part, the previously unexplained difference
      between concentrations of LAs required for their antiinflammatory action in vitro
      and in vivo. This study suggests a target site for LAs within a Gq-coupled
      signaling pathway.

PMID- 11465549
TI  - The gamma subunit determines whether anesthetic-induced leftward shift is altered
      by a mutation at alpha1S270 in alpha1beta2gamma2L GABA(A) receptors.
AB  - BACKGROUND: A major action of volatile anesthetics is enhancement of gamma
      aminobutyric acid receptor type A (GABA(A)R) currents. In recombinant GABA(A)Rs
      consisting of several subunit mixtures, mutating the alpha1 subunit serine at
      position 270 to isoleucine [alpha1(S270I)] was reported to eliminate anesthetic
      induced enhancement at low GABA concentrations. In the absence of studies at high
      GABA concentrations, it remains unclear whether alpha1(S270I) affects enhancement
      versus inhibition by volatile anesthetics. Furthermore, the majority of GABA(A)Rs
      in mammalian brain are thought to consist of alpha1, beta2, and gamma2 subunits,
      and the alpha1(S270I) mutation has not been studied in the context of this
      combination. METHODS: Recombinant GABA(A)Rs composed of alpha1beta2 or
      alpha1beta2gamma2L subunit mixtures were studied electrophysiologically in whole
      Xenopus oocytes in the voltage clamp configuration. Currents elicited by GABA
      (0.03 microM to 1 mM) were measured in the absence and presence of isoflurane or
      halothane. Anesthetic effects on GABA concentration responses were evaluated for
      individual oocytes. RESULTS: In wild-type alpha1beta2gamma2L GABA(A), anesthetics
      at approximately 2 minimum alveolar concentration (MAC) shifted GABA
      concentration response curves to the left approximately threefold, decreased the
      Hill coefficient, and enhanced currents at all GABA concentrations. The
      alpha1(S270I) mutation itself rendered the GABA(A)R more sensitive to GABA and
      reduced the Hill coefficient. At low GABA concentrations (EC5), anesthetic
      enhancement of peak current was much smaller in alpha1(S270I)beta2gamma2L versus
      wild-type channels. Paradoxically, the leftward shift of the whole GABA
      concentration-response relation by anesthetics was the same in both mutant and
      wild-type channels. At high GABA concentrations, volatile anesthetics reduced
      currents in alpha1(S270I)beta2gammaL GABA(A)Rs. In parallel studies on
      alpha1beta2 (gamma-less) GABA(A)Rs, anesthetic-induced leftward shifts in wild
      type receptors were more than eightfold at 2 MAC, and the alpha1(S270I) mutation
      nearly eliminated anesthetic-induced leftward shift. CONCLUSIONS: The results
      support a role for alpha1S270 in alpha1beta2gamma2L GABA(A)R gating and
      sensitivity to inhibition by volatile anesthetics. The alpha1S270 locus also
      modulates anesthetic enhancement in alpha1beta2 GABA(A)R. The presence of the
      gamma2L subunit reduces anesthetic-induced left shift of wild-type GABA(A)R and
      nullifies the impact of the alpha1(S2701) mutation on anesthetic modulation.
      Thus, the gamma2L subunit plays a significant role in GABA(A)R modulation by
      volatile anesthetic compounds.

PMID- 11465550
TI  - Effects of thoracic epidural anesthesia with and without autonomic nervous system
      blockade on cardiac monophasic action potentials and effective refractoriness in
      awake dogs.
AB  - BACKGROUND: The effects of thoracic epidural anesthesia (TEA) on myocardial
      repolarization and arrhythmogenicity are only incompletely understood. This is
      primarily because of the lack of appropriate experimental models. In most of the
      studies performed thus far, TEA was used in anesthetized animals. Baseline
      anesthesia itself may have modified the effects of TEA. This study investigates
      right atrial and ventricular repolarization by recording monophasic action
      potentials after TEA in awake dogs. The authors hypothesized that an
      antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA
      on myocardial repolarization. METHODS: The hypothesis was tested in an in vivo
      canine model, in which atrial and ventricular myocardial action potential
      duration and refractoriness are recorded by means of monophasic action potential
      catheters. RESULTS: Thoracic epidural anesthesia significantly increased
      ventricular monophasic action potential duration for cycle lengths shorter than
      350 ms. Changes in monophasic action potential duration were paralleled by a
      concomitant prolongation of effective refractory period (ERP) at higher rates so
      that the ratio of ERP to action potential duration was unaffected. CONCLUSIONS:
      This model helps to study the role of TEA on ventricular repolarization and
      arrhythmogenicity. Because lengthening of repolarization and prolongation of
      refractoriness may, in some circumstances, be antiarrhythmic, TEA may be
      protective against generation of ventricular arrhythmias mediated, e.g., by
      increased sympathetic tone. The results also imply that the beneficial role of
      TEA might be stronger at the ventricular site as compared with the atrium. At
      atrial sites there was only a trend toward prolongation of repolarization even at
      short cycle lengths.

PMID- 11465551
TI  - Effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents
      of the dorsal horn neurons in newborn rats.
AB  - BACKGROUND: Local anesthetics, such as bupivacaine, have been reported to block
      calcium currents in primary sensory neurons and to interfere with the release of
      neurotransmitters in central nervous system neurons. However, it is unknown
      whether local anesthetics affect the calcium current activity of central nervous
      system neurons. METHODS: Using a traditional whole cell voltage clamp technique,
      effects of bupivacaine and ropivacaine on high-voltage-activated calcium currents
      (HVA-Ic(a)) were investigated in enzymatically dissociated dorsal horn neurons of
      neonatal rats. Calcium currents were evoked by testing pulses from a holding
      potential of -90 to 0 mV. RESULTS: Bupivacaine significantly reduced HVA-Ic(a) in
      a dose-dependent manner. The peak HVA-Ic(a) decreased by 24.5+/-2.5, 32.0+/-6.8,
      59.4+/-6.2, 88.3+/-1.5, and 91.6+/-1.1% in response to 10, 30, 50, 100 and 200
      microM bupivacaine, respectively. Unlike bupivacaine, ropivacaine markedly
      increased HVA-Ic(a) at lower concentrations (< 50 microM) but decreased HVA-Ic(a)
      at higher concentrations (> or = 50 microM). The percent increases in peak HVA
      Ic(a) induced by 10 and 30 microM ropivacaine were 95+/-19.1 and 41.6+/-8.3%,
      respectively. The percent decreases in response to 50, 100, and 200 microM
      ropivacaine were 21.1+/-2.1, 63.2+/-6.0 and 79.1+/-7.6%, respectively. Results
      indicate that the inhibitory potency of ropivacaine on HVA-Ic(a) was
      significantly lower than that of bupivacaine at the same concentrations.
      CONCLUSIONS: The current study showed that bupivacaine inhibited HVA-Ic(a)
      recorded from dorsal horn neurons and that ropivacaine increased HVA-Ic(a) at
      lower concentrations but decreased HVA-Ic(a) at higher concentrations. The
      inhibitory potency of ropivacaine was lower than that of bupivacaine. Inhibition
      of calcium currents of central nervous system neurons may be related to the
      systemic neurotoxic effects of local anesthetics (e.g., convulsions, seizures).

PMID- 11465552
TI  - Differential effects of general anesthetics on G protein-coupled inwardly
      rectifying and other potassium channels.
AB  - BACKGROUND: General anesthetics differentially affect various families of
      potassium channels, and some potassium channels are suggested to be potential
      targets for anesthetics and alcohols. METHODS: The voltage-gated (ERG1, ELK1, and
      KCNQ2/3) and inwardly rectifying (GIRK1/2, GIRK1/4, GIRK2, IRK1, and ROMK1)
      potassium channels were expressed in Xenopus oocytes. Effects of volatile agents
      [halothane, isoflurane, enflurane, F3 (1-chloro-1,2,2-trifluorocyclobutane), and
      the structurally related nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane)],
      as well as intravenous (pentobarbital, propofol, etomidate, alphaxalone,
      ketamine), and gaseous (nitrous oxide) anesthetics and alcohols (ethanol and
      hexanol) on channel function were studied using a two-electrode voltage clamp.
      RESULTS: ERG1, ELK1, and KCNQ2/3 channels were either inhibited slightly or
      unaffected by concentrations corresponding to twice the minimum alveolar
      concentrations or twice the anesthetic EC50 of volatile and intravenous
      anesthetics and alcohols. In contrast, G protein-coupled inwardly rectifying
      potassium (GIRK) channels were inhibited by volatile anesthetics but not by
      intravenous anesthetics. The neuronal-type GIRK1/2 channels were inhibited by 2
      minimum alveolar concentrations of halothane or F3 by 45 and 81%, respectively,
      whereas the cardiac-type GIRK1/4 channels were inhibited only by F3. Conversely,
      IRK1 and ROMK1 channels were completely resistant to all anesthetics tested.
      Current responses of GIRK2 channels activated by mu-opioid receptors were also
      inhibited by halothane. Nitrous oxide (approximately 0.6 atmosphere) slightly but
      selectively potentiated GIRK channels. Results of chimeric and multiple amino
      acid mutations suggest that the region containing the transmembrane domains, but
      not the pore-forming domain, may be involved in determining differences in
      anesthetic sensitivity between GIRK and IRK channels. CONCLUSIONS: G protein
      coupled inwardly rectifying potassium channels, especially those composed of
      GIRK2 subunits, were inhibited by clinical concentrations of volatile
      anesthetics. This action may be related to some side effects of these agents.

PMID- 11465553
TI  - Enflurane actions on spinal cords from mice that lack the beta3 subunit of the
      GABA(A) receptor.
AB  - BACKGROUND: Gamma-aminobutyric acid type A (GABA(A)) receptors are considered
      important in mediating anesthetic actions. Mice lacking the beta3 subunit of this
      receptor (beta3-/-) have a higher enflurane minimum alveolar concentration (MAC)
      than wild types (+/+). MAC is predominantly determined in spinal cord. METHODS:
      The authors measured three population-evoked responses in whole spinal cords,
      namely, the excitatory postsynaptic potential (pEPSP), the slow ventral root
      potential (sVRP), and the dorsal root potential. Synaptic and glutamate-evoked
      currents from motor neurons in spinal cord slices were also measured. RESULTS:
      Sensitivity of evoked responses to enflurane did not differ between +/+ and -/-
      cords. The GABA(A) receptor antagonist bicuculline significantly (P < 0.05)
      attenuated the depressant effects of enflurane on pEPSP, sVRP and glutamate
      evoked currents in +/+ but not -/- cords. The glycine antagonist strychnine
      elevated the pEPSP to a significantly greater extent in -/- than in +/+ cords,
      but the interactions between strychnine and enflurane did not differ between -/-
      and +/+ cords. CONCLUSIONS: Similar enflurane sensitivity in spinal cords from -/
      and +/+ mice was coupled with a decreased role for GABA(A) receptors in
      mediating the actions of enflurane in the former. This finding implies that other
      anesthetic targets substitute for GABA(A) receptors. Increase in glycine receptor
      mediated inhibition was found in -/- cords, but the glycine receptor does not
      appear to be a substitute anesthetic target. This mutation thus led to a
      quantitative change in the molecular basis for anesthetic depression of spinal
      neurotransmission in a fashion not predicted by the mutation itself. The results
      argue against an immutable dominant role for GABA(A) receptors in mediating
      spinal contributions to MAC.

PMID- 11465554
TI  - Characterization of thioether compounds formed from alkaline degradation products
      of enflurane.
AB  - BACKGROUND: Renal toxicity has occasionally been observed after enflurane
      anesthesia. Although originally attributed to its oxidative metabolism to
      inorganic fluoride, serum levels of inorganic fluoride appear to be small to
      explain these renal effects. Formation of potentially nephrotoxic halogenated
      alkenes during alkaline degradation in carbon dioxide absorbers and subsequent
      bioactivation via the glutathione conjugation pathway may be considered as an
      alternative mechanism for renal toxicity. The aim of this study was to
      characterize the thioethers formed chemically and biosynthetically. METHODS:
      Alkaline degradation of enflurane was achieved by stirring with pulverized
      potassium hydroxide. Volatile degradation products were analyzed by 19F nuclear
      magnetic resonance (NMR) analysis of head space gasses trapped in dimethyl
      sulfoxide (DMSO). Thioethers were generated chemically by trapping head space
      gasses in DMSO containing N-acetyl-L-cysteine or 2-mercaptoacetic acid as model
      thiol compounds. Glutathione conjugates were generated biosynthetically by
      passing head space through rat liver fractions in presence of glutathione.
      Products formed were analyzed by gas chromatography-mass spectroscopy and 19F
      NMR. RESULTS: Direct analysis of head space gasses showed formation of 1-chloro
      1,2-difluorovinyl difluoromethyl ether and two unidentified fluorine-containing
      products as alkaline degradation products of enflurane. When trapped in DMSO-N
      acetyl-L-cysteine-triethylamine, N-acetyl-S-(2-chloro-1,2-difluoro-1
      (difluoromethoxy)ethyl)-L-cysteine was identified as the major product. Another N
      acetyl-L-cysteine S-conjugate formed was N-acetyl-S-(2-chloro-1,1,2
      trifluoroethyl)-L-cysteine, a potent nephrotoxin in rats. 19F-NMR analysis of
      glutathione conjugates formed after incubation with rat liver fractions resulted
      in formation of corresponding S-conjugates. CONCLUSIONS: The current study
      demonstrates that alkaline degradation products of enflurane can be conjugated to
      thiol compounds, forming S-conjugates that could theoretically contribute to
      adverse renal effects observed occasionally with enflurane anesthesia. The N
      acetyl-L-cysteine S-conjugates identified may be biomarkers to assess exposure of
      humans to alkaline degradation products of enflurane.

PMID- 11465555
TI  - Intravenous anesthetics inhibit nonadrenergic noncholinergic lower esophageal
      sphincter relaxation via nitric oxide-cyclic guanosine monophosphate pathway
      modulation in rabbits.
AB  - BACKGROUND: Nonadrenergic noncholinergic (NANC) nerves have important roles in
      the regulation of the lower esophageal sphincter (LES) motility and function. The
      effects of thiopental, ketamine, and midazolam on NANC LES relaxation were
      investigated. METHODS: The isometric tension of circular muscle strips from
      Japanese White rabbits was examined. The NANC relaxation was induced by KCl (30
      mM) in the presence of atropine (3 x 10(-6) M) and guanethidine (3 x 10(-6) M).
      The modifications of the NANC and sodium nitroprusside (SNP; 10(-5) M)-induced
      relaxation by the anesthetics were examined. The content of 3',5'-cyclic
      guanosine monophosphate (cGMP) was measured by radioimmunoassay. RESULTS: The KCl
      induced relaxation was abolished by pretreating with tetrodotoxin (10(-6) M). The
      NANC relaxation was inhibited in the presence of N(G)-nitro-L-arginine (L-NNA; 3
      x 10(-5) M), methylene blue (10(-6) M), apamin (10(-7) M), and glibenclamide (10(
      5) M). The SNP-induced relaxation was inhibited by methylene blue but was not
      affected by tetrodotoxin, L-NNA, apamin, or glibenclamide. Ketamine (EC50 = 8.8 x
      10(-5) M) and midazolam (EC50 = 4.8 x 10(-6) M) suppressed the NANC response in a
      concentration-dependent manner, leaving SNP-induced response unchanged.
      Thiopental altered neither of the relaxations. cGMP content was decreased in the
      presence of ketamine and midazolam. CONCLUSION: The NANC relaxation was mediated
      by nitric oxide and by low-conductance calcium- and adenosine triphosphate
      sensitive potassium channels of smooth muscle. The modulation of the nitric oxide
      cGMP pathway was related, at least in part, to the inhibitory actions of ketamine
      and midazolam on the NANC LES relaxation.

PMID- 11465556
TI  - Body morphology and the speed of cutaneous rewarming.
AB  - BACKGROUND: Infants and children cool quickly because their surface area (and
      therefore heat loss) is large compared with their metabolic rate, which is mostly
      a function of body mass. Rewarming rate is a function of cutaneous heat transfer
      plus metabolic heat production divided by body mass. Therefore, the authors
      tested the hypothesis that the rate of forced-air rewarming is inversely related
      to body size. METHODS: Isoflurane, nitrous oxide, and fentanyl anesthesia were
      administered to infants, children, and adults scheduled to undergo hypothermic
      neurosurgery. All fluids were warmed to 37 degrees C and ambient temperature was
      maintained near 21 degrees C. Patients were covered with a full-body, forced-air
      cover of the appropriate size. The heater was set to low or ambient temperature
      to reduce core temperature to 34 degrees C in time for dural opening. Blower
      temperature was then adjusted to maintain core temperature at 34 degrees C for 1
      h. Subsequently, the forced-air heater temperature was set to high (approximately
      43 degrees C). Rewarming continued for the duration of surgery and
      postoperatively until core temperature exceeded 36.5 degrees C. The rewarming
      rate in individual patients was determined by linear regression. RESULTS:
      Rewarming rates were highly linear over time, with correlations coefficients (r2)
      averaging 0.98+/-0.02. There was a linear relation between rewarming rate
      (degrees C/h) and body surface area (BSA; m2): Rate (degrees C/h) = -0.59 x BSA
      (m2) + 1.9, r2 = 0.74. Halving BSA thus nearly doubled the rewarming rate.
      CONCLUSIONS: Infants and children rewarm two to three times faster than adults,
      thus rapidly recovering from accidental or therapeutic hypothermia.

PMID- 11465557
TI  - Sedative but not analgesic alpha2 agonist tolerance is blocked by NMDA receptor
      and nitric oxide synthase inhibitors.
AB  - BACKGROUND: Studies show that the sedative and analgesic effects of alpha2
      adrenergic agonists decrease over time, which is a form of synaptic plasticity
      referred to as tolerance. Because both the N-methyl-D-aspartate (NMDA) receptor
      complex and nitric oxide synthase are pivotal for some forms of synaptic
      plasticity, their role in tolerance to the hypnotic and analgesic effects of
      alpha2 agonists was investigated. METHODS: After institutional approval, rats
      were made tolerant to the hypnotic or analgesic action of an alpha2 agonist,
      dexmedetomidine. The hypnotic response to dexmedetomidine was assessed by the
      duration of loss of righting reflex, and the analgesic response to
      dexmedetomidine was assessed by the tail-flick assay. In separate cohorts, either
      the NMDA receptors or nitric oxide synthase was antagonized by coadministration
      of MK-801, ketamine, or NO2-arginine, respectively, during induction of
      tolerance. In a separate series of experiments, after tolerance was induced, the
      hypnotic and analgesic responses to dexmedetomidine were assessed in the presence
      of acutely administered MK-801 or NO2-arginine. RESULTS: Induction of tolerance
      to the hypnotic effect of dexmedetomidine is blocked by coadministration of MK
      801, ketamine, and NO2-arginine. However, after tolerance developed, acute
      administration of MK-801, ketamine, or NO2-arginine did not prevent the
      expression of tolerance. Coadministration of MK-801 or NO2-arginine neither
      prevents the development nor reverses the expression of tolerance to the
      analgesic action of dexmedetomidine. CONCLUSION: The underlying processes
      responsible for the development of tolerance to the hypnotic and analgesic
      actions of systemically administered alpha2 agonists were different, with only
      the sedative tolerance involving the NMDA receptor and nitric oxide synthase
      system.

PMID- 11465558
TI  - Roles of carbon monoxide in leukocyte and platelet dynamics in rat mesenteric
      during sevoflurane anesthesia.
AB  - BACKGROUND: Heme oxygenase 1 (HO-1), induced by a variety of stressors, provides
      endogenous carbon monoxide (CO) and bilirubin, both of which play consequential
      roles in organs. The current study aimed to examine whether induction of HO-1 and
      its by-products modulated endothelial interaction with circulating leukocytes and
      platelets evoked by sevoflurane anesthesia in vivo. METHODS: Rats, pretreated
      with or without hemin, were anesthetized with sevoflurane in 100% O2, and lungs
      were mechanically ventilated. Platelets labeled with carboxyfluorescein diacetate
      succinimidyl ester and leukocyte behavior in mesenteric venules were visualized
      during sevoflurane anesthesia at 1,000 frames/s using intravital ultrahigh-speed
      intensified fluorescence videomicroscopy. To examine the mechanisms for the
      effects of HO-1 on leukocyte and platelet behavior, these studies were repeated
      with superfusion of either CO, bilirubin, or Nomega-nitro-L-arginine methyl ester
      (L-NAME). RESULTS: As reported previously, the elevation of sevoflurane
      concentration evoked adhesive responses of leukocytes, concurrent with platelet
      margination and rolling. Pretreatment with hemin, a HO-1 inducer, prevented such
      sevoflurane-elicited changes in the microvessels. These changes were restored by
      zinc protoporphyrin IX, a HO inhibitor, and repressed by CO but not by bilirubin.
      During sevoflurane anesthesia, however, nitric oxide suppression by L-NAME
      deteriorated microvascular flows irrespective of the presence or absence of the
      HO-1 induction. CONCLUSIONS: These results indicate that endogenous CO via HO-1
      induction attenuates sevoflurane-induced microvascular endothelial interactions
      with leukocytes and platelets, although local nitric oxide levels appear to
      dominate microvascular flow in situ.

PMID- 11465559
TI  - Mild alkalinization and acidification differentially modify the effects of
      lidocaine or mexiletine on vasorelaxation mediated by ATP-sensitive K+ channels.
AB  - BACKGROUND: The previous study by the authors showed that the class Ib
      antiarrhythmic drug lidocaine impairs but mexiletine augments vasorelaxation
      mediated by adenosine triphosphate-sensitive K+ channels. Lidocaine and
      mexiletine have different values of the negative logarithm of the drug-proton
      dissociation constant, indicating that the ion channel-blocking effects of these
      drugs under different pH levels may vary. However, the role of pH in the effects
      of lidocaine and mexiletine on vasodilation mediated by K+ channels has not been
      studied. Therefore, the current study was designed to examine whether the
      inhibition and augmentation of vasorelaxation in response to an adenosine
      triphosphate-sensitive K+ channel opener, levcromakalim, by the clinically
      relevant concentrations of lidocaine or mexiletine are modified by mild
      alkalinization or acidification in the isolated rat aorta. METHODS: Rings of the
      rat aorta without endothelium were suspended for isometric force recording. Three
      types of modified Krebs-Ringer solutions (pH 7.2, 7.4, and 7.6) were prepared by
      changing the composition of NaCl and NaHCO3. During contractions in response to
      phenylephrine (3 x 10(-7) M), relaxations in response to levcromakalim (10(-8) to
      10(-5) M) were obtained. Lidocaine (10(-5) to 10(-4) M), mexiletine (10(-5) to
      10(-4) M), or glibenclamide (10(-5) M) was applied 15 min before addition of
      phenylephrine. RESULTS: Relaxations in response to levcromakalim, which are
      abolished by the selective adenosine triphosphate-sensitive K+ channel antagonist
      glibenclamide (10(-5) M), were not different among the three pH groups. In the
      normal Krebs-Ringer solution of pH 7.4, lidocaine significantly reduced these
      relaxations in a concentration-dependent fashion. Alkalinization of pH 7.6
      augmented the inhibitory effect of lidocaine on these relaxations, whereas
      acidification of pH 7.2 substantially abolished this effect. In contrast,
      mexiletine pH independently augmented relaxations in response to levcromakalim.
      Glibenclamide (10(-5) M) abolished these relaxations in arteries treated with
      mexiletine (10(-4) M) in any pH group. CONCLUSIONS: These results suggest that
      even under conditions of such mild alkalosis or acidosis, vasorelaxation via
      adenosine triphosphate-sensitive K+ channels is dependent on pH in the presence
      of clinically relevant concentrations of lidocaine but not mexiletine.

PMID- 11465560
TI  - Effects of halothane on sarcoplasmic reticulum calcium release channels in
      porcine airway smooth muscle cells.
AB  - BACKGROUND: Volatile anesthetics relax airway smooth muscle (ASM) by altering
      intracellular Ca2+ concentration ([Ca2+]i). The authors hypothesized that
      relaxation is produced by decreasing sarcoplasmic reticulum Ca2+ content via
      increased Ca2+ "leak" through both inositol trisphosphate (IP3) and ryanodine
      receptor channels. METHODS: Enzymatically dissociated porcine ASM cells were
      exposed to acetylcholine in the presence or absence of 2 minimum alveolar
      concentration (MAC) halothane, and IP3 levels were measured using
      radioimmunoreceptor assay. Other cells were loaded with the Ca2+ indicator fluo-3
      and imaged using real-time confocal microscopy. RESULTS: Halothane increased IP3
      concentrations in the presence and absence of acetylcholine. Inhibition of
      phospholipase C blunted the IP3 response to halothane. Exposure to 2 MAC
      halothane induced a transient [Ca2+]i response, suggesting depletion of
      sarcoplasmic reticulum Ca2+. Exposure to 20 microM Xestospongin D, a cell
      permeant IP3 receptor antagonist, resulted in a 45+/-13% decrease in the [Ca2+]i
      response to halothane compared with halothane exposure alone. In permeabilized
      cells, Xestospongin D or 0.5 mg/ml heparin decreased the [Ca2+]i response to
      halothane by 65+/-13% and 68+/-22%, respectively, compared with halothane alone.
      In both intact and permeabilized cells, 20 microM ryanodine blunted the [Ca2+]i
      response to halothane by 32+/-13% and 39+/-21%, respectively, compared with
      halothane alone. Simultaneous exposure to Xestospongin D and ryanodine completely
      inhibited the [Ca2+]i response to halothane. CONCLUSIONS: The authors conclude
      that halothane reduces sarcoplasmic reticulum Ca2+ content in ASM cells via
      increased Ca2+ leak through both IP3 receptor and ryanodine receptor channels.
      Effects on IP3 receptor channels are both direct and indirect via elevation of
      IP3 levels.

PMID- 11465561
TI  - Gene therapy for the management of pain: part II: molecular targets.

PMID- 11465562
TI  - Comparison of five experimental pain tests to measure analgesic effects of
      alfentanil.
AB  - BACKGROUND: Several experimental pain models have been used to measure opioid
      effects in humans. The aim of the current study was to compare the qualities of
      five frequently used experimental pain tests to measure opioid effects. METHODS:
      The increase of electrical, heat, and pressure pain tolerance and the decrease of
      ice-water and ischemic pain perception was determined at baseline and at four
      different plasma concentrations of alfentanil (n = 7) administered as target
      controlled infusion or placebo (n = 7). A linear mixed-effects modeling (NONMEM)
      was performed to detect drug, placebo, and time effect as well as interindividual
      and intraindividual variation of effect. RESULTS: Only the electrical, ice-water,
      and pressure pain tests are sensitive to assess a concentration-response curve of
      alfentanil. At a plasma alfentanil concentration of 100 ng/ml, the increase in
      pain tolerance compared with baseline was 42.0% for electrical pain, 22.2% for
      pressure pain, and 21.7% for ice-water pain. The slope of the linear
      concentration-response curve had an interindividual coefficient of variation of
      58.3% in electrical pain, 35.6% in pressure pain, and 60.0% in ice-water pain.
      The residual error including intraindividual variation at an alfentanil
      concentration of 100 ng/ml was 19.4% for electrical pain, 6.1% for pressure pain,
      and 13.0% for ice-water pain. Electrical pain was affected by a significant
      placebo effect, and pressure pain was affected by a significant time effect.
      CONCLUSION: Electrical, pressure, and ice-water pain, but not ischemic and heat
      pain, provide significant concentration-response curves in the clinically
      relevant range of 200 ng/ml alfentanil or lower. The power to detect a clinically
      relevant shift of the curve is similar in the three tests. The appropriate
      test(s) for pharmacodynamic studies should be chosen according to the
      investigated drug(s) and the study design.

PMID- 11465563
TI  - Mechanism-based pain diagnosis: issues for analgesic drug development.

PMID- 11465564
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy.

PMID- 11465565
TI  - Perioperative management of severe head injury in a patient with arrhythmogenic
      right ventricular dysplasia.

PMID- 11465566
TI  - Postoperative sudden death in two adolescents with myelomeningocele and
      unrecognized arrhythmogenic right ventricular dysplasia.

PMID- 11465567
TI  - Drug-induced liver disease during continuous epidural block with bupivacaine.

PMID- 11465568
TI  - Regional pericarditis mimicking myocardial infarction.

PMID- 11465569
TI  - Severe, refractory hypotension during anesthesia in a patient on chronic
      clomipramine therapy.

PMID- 11465570
TI  - Spinal anesthesia at the cervicothoracic level.

PMID- 11465571
TI  - Perioperative temperature changes in a patient with Shapiro syndrome.

PMID- 11465572
TI  - Sedation caused by local anesthetic blockade.

PMID- 11465573
TI  - Thomas Drysdale Buchanan or Henry Isaiah Dorr: give credit to both.

PMID- 11465574
TI  - Airway bleeding in negative-pressure pulmonary edema.

PMID- 11465575
TI  - Precipitation of thiopental by rapacuronium.

PMID- 11465576
TI  - Hofmann, Schmofmann: atracurium undergoes Michael elimination.

PMID- 11465577
TI  - Use of the esophageal Doppler with the LMA-ProSeal.

PMID- 11465578
TI  - Society for Education in Anesthesia Annual Fall Meeting and Workshops. San
      Francisco, California. October 13, 2000.

PMID- 11465579
TI  - New mechanisms for inhaled NO: release of an endogenous NO inhibitor?

PMID- 11465580
TI  - Shannon entropy applied to the measurement of the electroencephalographic effects
      of desflurane.
AB  - BACKGROUND: The Shannon entropy is a standard measure for the order state of
      sequences. It quantifies the degree of skew of the distribution of values.
      Increasing hypnotic drug concentrations increase electroencephalographic
      amplitude. The probability density function of the amplitude values broadens and
      flattens, thereby changing from a skew distribution towards equal distribution.
      We investigated the dose-response relation of the Shannon entropy of the
      electroencephalographic amplitude values during desflurane monoanesthesia in
      comparison with previously used electroencephalographic parameters. METHODS:
      Electroencephalographic records previously obtained in 12 female patients during
      gynecologic laparotomies were reanalyzed. Between opening and closure of the
      peritoneum, desflurane vapor settings were varied between 0.5 and 1.6 minimum
      alveolar concentration. Electroencephalographic Shannon entropy, approximate
      entropy, median electroencephalographic frequency, SEF 95, total power, log total
      power, and Bispectral Index were determined, and their correlations with the
      desflurane effect compartment concentration, obtained by simultaneous
      pharmacokinetic-pharmacodynamic modeling, were compared. RESULTS: The
      electroencephalographic Shannon entropy increased continuously over the observed
      concentration range of desflurane. The correlation of the Shannon entropy (R2 =
      0.84+/-0.08, mean +/- SD) with the desflurane effect compartment concentrations
      is similar to approximate entropy (R2 = 0.85+/-0.12), SEF 95 (R2 = 0.85+/-0.10),
      and Bispectral Index (R2 = 0.82+/-0.13) and is more statistically significant
      than median frequency (R2 = 0.72+/-0.17), total power (R2 = 0.67+/-0.18), and log
      total power (R2 = 0.80+/-0.09). CONCLUSIONS: The Shannon entropy seems to be a
      useful electroencephalographic measure of anesthetic drug effect.

PMID- 11465581
TI  - The validity of performance assessments using simulation.
AB  - BACKGROUND: The authors wished to determine whether a simulator-based evaluation
      technique assessing clinical performance could demonstrate construct validity and
      determine the subjects' perception of realism of the evaluation process. METHODS:
      Research ethics board approval and informed consent were obtained. Subjects were
      33 university-based anesthesiologists, 46 community-based anesthesiologists, 23
      final-year anesthesiology residents, and 37 final-year medical students. The
      simulation involved patient evaluation, induction, and maintenance of anesthesia.
      Each problem was scored as follows: no response to the problem, score = 0;
      compensating intervention, score = 1; and corrective treatment, score = 2.
      Examples of problems included atelectasis, coronary ischemia, and hypothermia.
      After the simulation, participants rated the realism of their experience on a 10
      point visual analog scale (VAS). RESULTS: After testing for internal consistency,
      a seven-item scenario remained. The mean proportion scoring correct answers (out
      of 7) for each group was as follows: university-based anesthesiologists = 0.53,
      community-based anesthesiologists = 0.38, residents = 0.54, and medical students
      = 0.15. The overall group differences were significant (P < 0.0001). The overall
      realism VAS score was 7.8. There was no relation between the simulator score and
      the realism VAS (R = -0.07, P = 0.41). CONCLUSIONS: The simulation-based
      evaluation method was able to discriminate between practice categories,
      demonstrating construct validity. Subjects rated the realism of the test scenario
      highly, suggesting that familiarity or comfort with the simulation environment
      had little or no effect on performance.

PMID- 11465582
TI  - A randomized, controlled trial of advanced care planning discussions during
      preoperative evaluations.
AB  - BACKGROUND: Although many patients and physicians support the concept of advance
      care planning, only a small percentage of patients actually have the necessary
      discussion with health care providers. Hospital-based physicians other than
      primary care providers often are needed to increase physician, patient, and proxy
      communication about advanced directives. This study evaluated the effectiveness
      of a 5-10-min discussion designed to foster dialogue between patients and their
      proxies in a preoperative evaluation clinic. The discussions were lead by
      anesthesiologists. METHODS: A randomized controlled trial was conducted from
      September 1998 through May 1999 in a preoperative evaluation clinic at University
      of California, San Francisco, a tertiary care center. English-speaking patients
      aged 65 yr or older who were scheduled for elective surgery were randomized to
      receive a short information session stressing the importance of communication
      about end-of-life care between the patients and their proxies. Patients
      randomized to the control group received the standard preoperative anesthesia
      screening. An admitting counselor questioned all patients (control and
      intervention) about whether they have an advanced directive as part of the
      registration process before their arrival in clinic. RESULTS: The intervention
      significantly increased discussions about end-of-life care between patients and
      their proxies. Eighty seven percent of patients reported having discussions with
      their proxies as compared with only 66% of control patients (P = 0.001). The
      intervention also increased durable power of attorney completion rate to 27% as
      compared with 10% completion rate by controls. CONCLUSIONS: The preoperative
      evaluation period can be an opportunity to encourage patient and proxy
      communication about end-of-life care.

PMID- 11465583
TI  - Moderate hypothermia depresses arterial baroreflex control of heart rate during,
      and delays its recovery after, general anesthesia in humans.
AB  - BACKGROUND: Effects of hypothermia on arterial baroreflex function during, and on
      its recovery after, general anesthesia were examined in humans. METHODS: Twenty
      healthy volunteers were randomly assigned to a normothermic group (n = 10 each,
      active forced-air warming) or to a hypothermic group (no active warming) during
      anesthesia. Measurements of R-R intervals and systolic blood pressure were made
      at conscious baseline and at 20, 60, and 120 min after the induction and 20, 60,
      120, and 180 min after emergence from general anesthesia with sevoflurane for 2
      h. Ventilation was mechanically controlled, and end-tidal sevoflurane
      concentration was maintained at 2% during anesthesia. Baroreflex responses were
      triggered by bolus intravenous injections of phenylephrine and nitroprusside. The
      linear portions of the baroreflex curves relating R-R intervals and systolic
      blood pressure were determined to obtain baroslopes. RESULTS: During anesthesia,
      the mean lowest tympanic temperature of the hypothermia group (33.9+/-0.5 degrees
      C [mean +/- SD]) was significantly lower than that of the normothermia group
      (36.1+/-0.7 degrees C, P < 0.001). The baroslopes of the pressor and depressor
      tests were decreased by 19-39% during and by 27-53% after general anesthesia in
      the hypothermia group, compared with the normothermia group (P < 0.05). The
      baroslopes of the normothermia group returned to the baseline values at 60 min
      after anesthesia, whereas the pressor test sensitivity of the hypothermia group
      was significantly less than that of the normothermia group for the entire course
      of recovery. CONCLUSIONS: The results indicate that moderate hypothermia enhances
      anesthesia-induced depression of baroreflex function in anesthetized humans and
      delays its recovery after general anesthesia.

PMID- 11465584
TI  - Distribution of the probability of survival is a strategic issue for randomized
      trials in critically ill patients.
AB  - BACKGROUND: Many randomized clinical trials in trauma have failed to demonstrate
      a significant improvement in survival rate. Using a trauma patient database, we
      simulated what could happen in a trial designed to improve survival rate in this
      setting. METHODS: The predicted probability of survival was assessed using the
      TRISS methodology in 350 severely injured trauma patients. Using this probability
      of survival, the authors simulated the effects of a drug that may increase the
      probability of survival by 10-50% and calculated the number of patients to be
      included in a triad, assuming alpha = 0.05 and beta = 0.10 by using the
      percentage of survivors or the individual probability of survival. Other
      distributions (Gaussian, J shape, uniform) of the probability of survival were
      also simulated and tested. RESULTS: The distribution of the probability of
      survival was bimodal with two peaks (< 0.10 and > 0.90). There were major
      discrepancies between the number of patients to be included when considering the
      percentage of survivors or the individual value of the probability of survival:
      63,202 versus 2,848 if the drug increases the probability of survival by 20%.
      This discrepancy also occurred in other types of distribution (uniform, J shape)
      but to a lesser degree, whereas it was very limited in a Gaussian distribution.
      CONCLUSIONS: The bimodal distribution of the probability of survival in trauma
      patients has major consequences on hypothesis testing, leading to overestimation
      of the power. This statistical pitfall may also occur in other critically ill
      patients.

PMID- 11465585
TI  - Comparison of closed-loop controlled administration of propofol using Bispectral
      Index as the controlled variable versus "standard practice" controlled
      administration.
AB  - BACKGROUND: This report describes a new closed-loop control system for propofol
      that uses the Bispectral Index (BIS) as the controlled variable in a patient
      individualized, adaptive, model-based control system, and compares this system
      with manually controlled administration of propofol using hemodynamic and somatic
      changes to guide anesthesia. METHODS: Twenty female patients, American Society of
      Anesthesiologists physical status I or II, who were scheduled for gynecologic
      laparotomy were included to receive propofolremifentanil anesthesia. In group I,
      propofol was titrated using a BIS-guided, model-based, closed-loop system. The
      BIS target was set at 50. In group II, propofol was titrated using classical
      hemodynamic signs of (in)adequate anesthesia. Performance of control during
      induction and maintenance of anesthesia were compared between both groups using
      BIS as the controlled variable in group I and the reference variable in group II,
      and, conversely, the systolic blood pressure as the controlled variable in group
      II and the reference variable in group I. At the end of anesthesia, recovery
      profiles between groups were compared. RESULTS: Although patients undergoing
      manual induction of anesthesia in group II at 300 ml/h reached a BIS level of 50
      faster than patients undergoing open-loop, computer-controlled induction in group
      I, manual induction caused a more pronounced initial overshoot of the BIS target.
      This resulted in a more pronounced decrease in blood pressure in group II. During
      the maintenance phase, better control of BIS and systolic blood pressure was
      found in group I compared with group II. Recovery was faster in group I.
      CONCLUSION: A closed-loop system for propofol administration using the BIS as a
      controlled variable together with a model-based controller is clinically
      acceptable during general anesthesia.

PMID- 11465586
TI  - Anaphylactic reactions to aprotinin reexposure in cardiac surgery: relation to
      antiaprotinin immunoglobulin G and E antibodies.
AB  - BACKGROUND: Aprotinin, a serine proteinase inhibitor, reduces bleeding during
      cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic
      properties. This investigation examined the incidence of anaphylactic reactions
      in patients reexposed to aprotinin and the relation to preformed antiaprotinin
      immunoglobulin (Ig)G and IgE antibodies. METHODS: This prospective observational
      study conducted at five centers in Germany evaluated patients undergoing repeat
      cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG
      and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent
      assay and an immunofluorescence assay, respectively, were performed
      preoperatively and postoperatively. An anaphylactic reaction was defined as major
      changes from baseline within 10 min of aprotinin administration of systolic
      pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater
      than 5 cm H2O, or a skin reaction. RESULTS: In 121 cases (71 adults, 46
      children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136
      days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3)
      and IgE antibodies (radioallergosorbent test [RAST] score < 3) were detected in
      18 and 9 patients, respectively. High concentrations of each (IgG, optical
      density ratio > 10; IgE, RAST score > or = 3) were detected in five patients.
      Three patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an
      anaphylactic reaction after aprotinin exposure, followed by full recovery; these
      patients had reexposure intervals less than 6 months (22, 25, and 25 days) and
      the highest preoperative IgG concentrations of all patients (P < 0.05). Assay
      sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative
      patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%.
      Preoperative IgE measurements were quantifiable in two of three reactive patients
      and in three nonreacting patients. CONCLUSIONS: Quantitative detection of
      antiaprotinin IgE and IgG lacks specificity for predictive purposes; however,
      quantitation of antiaprotinin IgG may identify patients at risk for developing an
      anaphylactic reaction to aprotinin reexposure.

PMID- 11465587
TI  - Impact of spinal cord stimulation on sensory characteristics in complex regional
      pain syndrome type I: a randomized trial.
AB  - BACKGROUND: A randomized trial was performed to assess the effect of spinal cord
      stimulation (SCS) on detection and pain thresholds for pressure, warmth, and cold
      and on the extent of mechanical hyperalgesia in patients with chronic complex
      regional pain syndrome type I. METHODS: Fifty-four chronic complex regional pain
      syndrome type I patients were randomized to receive both SCS and physical therapy
      (SCS+PT; n = 36), or to receive only physical therapy (PT; n = 18). Twenty-four
      SCS+PT patients responded positively to trial stimulation and underwent SCS
      implantation. During a 12-month follow-up period, six quantitative sensory
      testing sessions were performed. The main analysis compared 24 SCS patients with
      29 nonimplanted patients--one PT patient was excluded. RESULTS: SCS showed no
      effect on detection thresholds for warmth and cold or on pain thresholds for any
      sensation. The pressure detection threshold initially increased by SCS, but after
      3 months, pressure detection thresholds returned to normal. Mechanical
      hyperalgesia, both dynamic and static, was reduced slightly with SCS.
      CONCLUSIONS: Although SCS has previously been shown to cause a significant pain
      reduction in complex regional pain syndrome type I, the treatment has no long
      term effect on detection and pain thresholds for pressure, warmth, or cold. The
      treatment seems to have only minimal influence on mechanical hyperalgesia.

PMID- 11465588
TI  - Failure of autologous fresh frozen plasma to reduce blood loss and transfusion
      requirements in coronary artery bypass surgery.
AB  - BACKGROUND: Previous studies failed to demonstrate any benefit from prophylaxis
      with fresh frozen plasma (FFP) after cardiopulmonary bypass (CPB). The results,
      however, were limited by either retrospective study design or use of FFP in
      subtherapeutic doses (2-3 units). The authors evaluated whether a therapeutic
      dose (15 ml/kg) of FFP reduces blood loss and transfusion requirements in
      elective coronary artery bypass surgery. The risks of multiple allogeneic blood
      donor exposure were circumvented by using autologous plasma. METHODS: Sixty adult
      patients scheduled for elective primary coronary artery bypass grafting were
      randomized to receive, after CPB, an intravenous infusion of 15 ml/kg of either
      autologous FFP (30 patients) or 6% hydroxyethyl starch 450/0.7 (HES; 30
      patients). Autologous plasma was obtained by platelet-poor plasmapheresis several
      weeks before surgery. Perioperative blood transfusions were administered per
      protocol. Postoperative blood loss was defined as the chest tube drainage during
      the first 24 h after surgery. RESULTS: The data from 56 patients (FFP group, 27
      patients; HES group, 29 patients) who completed the study according to protocol
      were analyzed. Median postoperative blood loss was 630 ml (range, 450-1,840 ml)
      and 830 ml (range, 340-1,980 ml) in the FFP and HES groups, respectively (P =
      0.08). Both postoperative (0-24 h) and total perioperative erythrocyte
      transfusion requirements did not differ significantly between the groups (P =
      0.32 and 0.14, respectively). CONCLUSION: The prophylactic administration of a
      therapeutic dose (15 ml/kg) of autologous FFP after CPB failed to reduce blood
      loss and transfusion requirements in patients undergoing uncomplicated, elective,
      primary coronary artery bypass surgery.

PMID- 11465589
TI  - Pharmacokinetics of bupivacaine after continuous epidural infusion in infants
      with and without biliary atresia.
AB  - BACKGROUND: Continuous epidural infusion of bupivacaine is widely practiced for
      postoperative pain relief in pediatric patients. However, bupivacaine may induce
      adverse effects in infants (convulsions or cardiac arrhythmias), likely because
      of decreased hepatic clearance and serum protein binding capacity. The authors
      wanted to examine the complex relations between age, alpha-1 acid glycoprotein
      (AAG) concentration, and unbound and total bupivacaine serum concentrations in
      infants receiving bupivacaine epidurally for 2 days. METHODS: Twenty-two infants
      aged 1-7 months (12 with biliary atresia and 10 with another disease) received a
      continuous epidural infusion of 0.375 mg x kg(-1) x h(-1) bupivacaine during 2
      days (during and after surgery). Unbound and total bupivacaine concentration in
      serum was measured 0.5, 4, 24, and 48 h after infusion initiation. AAG
      concentration was measured in serum before and 2 days after surgery. In eight
      additional infants, the blood/plasma concentration ratio was measured in vitro at
      whole blood concentrations of 2 and 20 microg/ml. Bupivacaine concentration was
      fitted to a one-compartment model to calculate basic pharmacokinetic parameters.
      RESULTS: No adverse effects were observed. AAG increased markedly after surgery,
      and the increase was correlated to both age and preoperative AAG concentration.
      Two infants aged 1.8 months had unbound concentrations greater than 0.2
      microg/ml. Clearance of unbound drug significantly increased with age. Because of
      increased drug binding, clearance of bound drug decreased both with time (from
      0.5 to 48 h) and with age. Blood/plasma ratio was 0.77+/-0.08 and 0.85+/-0.24 at
      2 and 20 microg/ml, respectively. CONCLUSIONS: Because of a low AAG concentration
      and a low intrinsic clearance, unbound bupivacaine increased to concentrations
      greater than 0.2 microg/ml in two infants younger than 2 months, after 2 days of
      infusion at a rate of 0.375 mg x kg(-1) x h(-1). The increase in AAG observed
      after surgery did not fully buffer this unbound fraction. Similarly, the buffer
      capacity of erythrocytes did not sufficiently increase at high concentration to
      compensate the saturation of the AAG system. Thus, we propose the use of a
      maximum dose of 0.25 mg x kg(-1) x h(-1) in infants younger than 4 months and a
      maximum of 0.3 mg x kg(-1) x h(-1) in infants older than 4 months.

PMID- 11465590
TI  - The corrugator supercilii, not the orbicularis oculi, reflects rocuronium
      neuromuscular blockade at the laryngeal adductor muscles.
AB  - BACKGROUND: Some studies suggest that the orbicularis oculi is resistant to
      neuromuscular blocking drugs and behaves like laryngeal muscles. Others report
      little or no difference between the orbicularis oculi and the adductor pollicis.
      These discrepancies could be related to the exact site of recording. The purpose
      of this study was to compare two monitoring sites around the eye with the
      adductor pollicis and the laryngeal adductor muscles. METHODS: After
      institutional approval and informed consent, the evoked response to train-of-four
      stimulation was measured in 12 patients by acceleromyography at the thumb
      (adductor pollicis), the eyelid (orbicularis oculi), and the superciliary arch
      (corrugator supercilii) after 0.5 mg/kg rocuronium during propofol-fentanyl
      nitrous oxide anesthesia. In 12 other patients, laryngeal adductor neuromuscular
      blockade was assessed via the cuff of the tracheal tube and compared with the
      adductor pollicis and the corrugator supercilii after 0.6 mg/kg rocuronium.
      RESULTS: After 0.5 mg/kg, maximum blockade (%T1, mean +/- SD) was less at the
      corrugator supercilii (80+/-20%) than at the adductor pollicis (100+/-1%) and the
      orbicularis oculi (93+/-8%) (P < 0.01). Clinical duration (25%T1) was shorter at
      the corrugator supercilii (12+/-7 min) than at the adductor pollicis (25+/-4 min)
      and orbicularis oculi (24+/-10 min) (P < 0.01). After 0.6 mg/kg, maximum blockade
      was similar at the corrugator supercilii (88+/-8%) and the laryngeal adductor
      muscles (89+/-11%). Clinical duration at the corrugator supercilii and the
      laryngeal adductors was 17+/-7 and 17+/-10 min, respectively. CONCLUSIONS:
      Muscles around the eye vary in their response to rocuronium. The response of the
      superciliary arch (corrugator supercilii) reflects blockade of laryngeal adductor
      muscles. However, the eyelid (orbicularis oculi) and thumb (adductor pollicis)
      have similar sensitivities.

PMID- 11465591
TI  - Lack of degradation of sevoflurane by a new carbon dioxide absorbent in humans.
AB  - BACKGROUND: Potent inhaled anesthetics degrade in the presence of the strong
      bases (sodium hydroxide or potassium hydroxide) in carbon dioxide (CO2)
      absorbents. A new absorbent, Amsorb (Armstrong Medical Ltd., Coleraine, Northern
      Ireland), does not employ these strong bases. This study compared the scavenging
      efficacy and compound A production of two commercially available absorbents (soda
      lime and barium hydroxide lime) with Amsorb in humans undergoing general
      anesthesia. METHODS: Four healthy volunteers were anesthetized on different days
      with desflurane, sevoflurane, enflurane, and isoflurane. End-tidal carbon dioxide
      (ETCO2) and anesthetic concentrations were measured with infrared spectroscopy;
      blood pressure and arterial blood gases were obtained from a radial artery
      catheter. Each anesthetic exposure lasted 3 h, during which the three fresh
      (normally hydrated) CO2 absorbents were used for a period of 1 h each. Anesthesia
      was administered with a fresh gas flow rate of 2 l/min of air:oxygen (50:50).
      Tidal volume was 10 ml/kg; respiratory rate was 8 breaths/min. Arterial blood
      gases were obtained at baseline and after each hour. Inspired concentrations of
      compound A were measured after 15, 30, and 60 min of anesthetic administration
      for each CO2 absorbent. RESULTS: Arterial blood gases and ETCO2 were not
      different among three CO2 absorbents. During sevoflurane, compound A formed with
      barium hydroxide lime and soda lime, but not with Amsorb. CONCLUSIONS: This new
      CO2 absorbent effectively scavenged CO2 and was not associated with compound A
      production.

PMID- 11465592
TI  - Effect of the deficiency of spinal PSD-95/SAP90 on the minimum alveolar
      anesthetic concentration of isoflurane in rats.
AB  - BACKGROUND: Spinal N-methyl-D-aspartate (NMDA) receptor activation has been
      demonstrated to play an important role in the processing of spinal nociceptive
      information and in the determination of the minimum alveolar anesthetic
      concentration (MAC) of inhalational anesthetics. Postsynaptic density-95 (PSD
      95)/synapse-associated protein-90 (SAP90), a molecular scaffolding protein that
      binds and clusters the NMDA receptor perferentially at synapses, was implicated
      in NMDA-induced thermal hyperalgesia. The current study investigated the possible
      involvement of PSD-95/SAP9O in determining MAC for isoflurane anesthesia.
      METHODS: Sprague-Dawley rats were pretreated intrathecally with PSD-95/SAP90
      antisense oligodeoxyribonucleotide (ODN), sense ODN, missense ODN, or saline
      every 24 h for 4 days. After initial baseline determination of the MAC, NMDA or
      saline was injected intrathecally. Ten minutes later, MAC measurement was
      repeated. The rats also were evaluated for the presence of locomotor dysfunction
      by intrathecal administration of NMDA or saline in the saline- and ODN-treated
      rats. RESULTS: In the groups treated with antisense ODNs, but not in those
      treated with sense or missense ODNs, there was a significant decrease in
      isoflurane MAC that was not accompanied by marked changes in either blood
      pressure or heart rate. In the saline-treated group, intrathecal NMDA caused an
      increase in isoflurane MAC. In contrast, in the antisense ODN-treated group,
      intrathecal NMDA did not produce a significant change in isoflurane MAC. An NMDA
      induced increase in blood pressure but not heart rate was found in both saline-
      and antisense ODN-treated groups. Locomotor activity was not changed in any of
      the treated animals. CONCLUSION: The results indicate not only a significant
      decrease in MAC for isoflurane but also an attenuation in the NMDA-induced
      increase in isoflurane MAC in the PSD-95/SAP90 antisense-treated animals, which
      suggests that PSD-95/SAP90 may mediate the role of the NMDA receptor in
      determining the MAC of inhalational anesthetics.

PMID- 11465593
TI  - Role of heparin and nitric oxide in the cardiac and regional hemodynamic
      properties of protamine in conscious chronically instrumented dogs.
AB  - BACKGROUND: Because protamine is administered to reverse heparin, a drug that
      might itself affect the pharmacologic properties of protamine, this study was
      designed to assess the properties of protamine alone and in the presence of
      heparin in conscious dogs. METHODS: Twelve dogs were instrumented to continuously
      record cardiac and regional hemodynamics. On separate occasions, a dose of
      protamine (0.5, 1, 3, 5, and 8 mg/kg) was randomly administered either alone or
      in the presence of heparin (ratio 100 IU/mg). Heparin (300 IU/kg) and protamine
      (3 mg/kg) were administered in the presence of N-methyl-L-arginine, a specific
      nitric oxide synthase inhibitor. Identical experiments were performed with
      protamine (8 mg/kg) in the absence of heparin on a separate occasion. RESULTS:
      Protamine alone produced limited cardiac and regional changes. In the presence of
      heparin, protamine produced hypotension at 3, 5, and 8 mg/kg, vasodilatation at 3
      and 5 mg/kg, and a more pronounced dose-dependent increase in pulmonary pressure
      at 3, 5, and 8 mg/kg. Simultaneously, transient carotid vasodilatation at 3 and 5
      mg/kg, coronary and hepatic vasodilatation at 3, 5, and 8 mg/kg, as well as a
      decrease in vertebral vascular resistance were recorded at 1, 3, and 8 mg/kg.
      Protamine produced an immediate increase followed by a secondary decrease in
      renal vascular resistance. Protamine-induced secondary pulmonary pressor effects
      were attenuated. In the presence of heparin, nitric oxide synthase blockade
      selectively attenuated protamine-induced immediate hypotension, systemic
      vasodilatation, and coronary, mesenteric, and hepatic vasodilations as well as
      the decrease in portal blood flow and accentuated the renal vasoconstriction.
      CONCLUSIONS: The presence of heparin accentuated the decrease in cardiac function
      induced by protamine as well as its effects on regional circulation. The data
      provide evidence that the nitric oxide pathway is involved in the systemic and
      selective regional heparin-protamine-mediated vasodilatation in conscious dogs.

PMID- 11465594
TI  - Divergence of volatile anesthetic effects in inhibitory neurotransmitter
      receptors.
AB  - BACKGROUND: The mechanism of volatile anesthetic (VA) action is unknown.
      Inhibitory receptors for the neurotransmitters gamma-aminobutyric acid (GABA) or
      glycine are typically positively modulated by VAs and may be important targets
      for their action. The existence of a GABA receptor subtype (p), which is uniquely
      inhibited by VAs, suggested a chimeric receptor approach to identify portions of
      these proteins that may be necessary for anesthetic effects. METHODS: A silent
      mutation resulting in the addition of a unique restriction enzyme recognition
      site was introduced in GABA receptor type A alpha2, glycine alpha1, and p subunit
      cDNAs. Chimeras were constructed by rejoining restriction digest fragments and
      were expressed in Xenopus oocytes. Modulation of submaximal agonist-evoked peak
      currents by the VAs chloroform, enflurane, halothane, or isoflurane was measured
      using two-electrode voltage clamp. RESULTS: Four chimeras were constructed and
      designated glyrho, rhogly, alpha2rho, and rhoalpha2. Glyrho formed glycine-gated
      receptors with currents that were enhanced by chloroform or halothane but were
      inhibited by enflurane or isoflurane. Chimeras rhogly and rhoalpha2 each formed
      GABA-gated receptors with currents that were inhibited by chloroform or halothane
      but enhanced by enflurane or isoflurane. CONCLUSIONS: These data show, for the
      first time, functional divergence of VA action on a single protein target. The
      VAs in this study fall into two distinct groups with respect to their effects on
      these receptors. This grouping parallels the chemistry of these compounds. Our
      results support the involvement of multiple protein domains in the mechanism of
      VA modulation of GABA and glycine receptors.

PMID- 11465595
TI  - Analgesic and antiinflammatory effects of two novel kappa-opioid peptides.
AB  - BACKGROUND: This study investigates two new kappa-agonist tetrapeptides, FE
      200665 and FE 200666, with high peripheral selectivity as a result of poor
      central nervous system penetration. METHODS: Four days after administration of
      Freund adjuvant into the hind paw of male Wistar rats, antinociceptive effects of
      intraplantar and subcutaneous injection of FE 200665 and FE 200666 were measured
      by paw pressure algesiometry and compared with the kappa-agonist U-69,593.
      Peripheral and kappa-receptor selectivity was assessed by the antagonists
      naloxone methiodide (NLXM) and nor-binaltorphimine, respectively.
      Antiinflammatory effects were evaluated by paw volume plethysmometry and
      histologic score. RESULTS: Similar to intraplantar U-69,593, intraplantar FE
      200665 (3-100 microg) and FE 200666 (1-30 microg) resulted in significant and
      dose-related increases of paw pressure thresholds. Higher doses of FE 200665 (0.2
      20 mg) and FE 200666 (0.06-6 mg) were required by subcutaneous route to produce
      similar antinociceptive responses, supporting a peripheral site of action. nor
      Binaltorphimine dose-dependently antagonized this effect, implying kappa-opioid
      selectivity. Analgesic effects of subcutaneous FE 200665 and FE 200666 were
      abolished by intraplantar nor-binaltorphimine, and both subcutaneous and
      intraplantar effects were dose-dependently antagonized by subcutaneous NLXM,
      further demonstrating a peripheral site of action. One to 6 days after Freund
      adjuvant inoculation, single and repeated intraplantar injections of FE 200665,
      FE 200666, and U-69,593 significantly reduced paw volume and histologic scores.
      Both changes were reversed by intraplantar nor-binaltorphimine and subcutaneous
      NLXM. CONCLUSION: FE 200665 is a peripherally selective kappa-agonist with potent
      analgesic and antiinflammatory properties that may lead to improved analgesic
      antiinflammatory therapy compared with centrally acting opioids or standard
      nonsteroidal antiinflammatory drugs.

PMID- 11465596
TI  - Partial liquid ventilation reduces fluid filtration of isolated rabbit lungs with
      acute hydrochloric acid-induced edema.
AB  - BACKGROUND: Hydrochloric acid aspiration increases pulmonary microvascular
      permeability. The authors tested the hypothesis that partial liquid ventilation
      has a beneficial effect on filtration coefficients in acute acid-induced lung
      injury. METHODS: Isolated blood-perfused rabbit lungs were assigned randomly to
      one of four groups. Group 1 (n = 6) served as a control group without edema. In
      group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6), pulmonary edema was
      induced by intratracheal instillation of hydrochloric acid (0.1 N, 2 ml/kg body
      weight). Filtration coefficients were determined 30 min after this injury (by
      measuring loss of perfusate after increase of left atrial pressure). Group 2
      lungs were gas ventilated, and group 3 lungs received partial liquid ventilation
      (15 ml perfluorocarbon/kg body weight). In group 4 lungs, the authors studied the
      immediate effects of bronchial perfluorocarbon instillation on ongoing
      filtration. RESULTS: Intratracheal instillation of hydrochloric acid markedly
      increased filtration coefficients when compared with non-injured control lungs
      (2.3 +/- 0.7 vs. 0.31 +/- 0.08 ml.min(-1). mmHg(-1).100 g(-1) wet lung weight, P
      < 0.01). Partial liquid ventilation reduced filtration coefficients of the
      injured lungs (to 0.9 +/- 0.3 ml.min(-1).mmHg(-1).100 g(-1) wet lung weight, P =
      0.022). Neither pulmonary artery nor capillary pressures (determined by
      simultaneous occlusion of inflow and outflow of the pulmonary circulation) were
      changed by hydrochloric acid instillation or by partial liquid ventilation.
      During ongoing filtration, bronchial perfluorocarbon instillation (5 ml/kg body
      weight) immediately reduced the amount of filtered fluid by approximately 50% (P
      = 0.027). CONCLUSIONS: In the acute phase after acid injury, partial liquid
      ventilation reduced pathologic fluid filtration. This effect started immediately
      after bronchial perfluorocarbon instillation and was not associated with changes
      in mean pulmonary artery, capillary, or airway pressures. The authors suggest
      that in the early phase of acid injury, reduction of fluid filtration contributes
      to the beneficial effects of partial liquid ventilation on gas exchange and lung
      mechanics.

PMID- 11465597
TI  - Anesthetic properties of 4-iodopropofol: implications for mechanisms of
      anesthesia.
AB  - BACKGROUND: Positive modulation of gamma-aminobutyric acid type A (GABAA)
      receptor function is recognized as an important component of the central nervous
      system depressant effects of many general anesthetics, including propofol. The
      role for GABAA receptors as an essential site in the anesthetic actions of
      propofol was recently challenged by a report that the propofol analog 4
      iodopropofol (4-iodo-2,6-diisopropylphenol) potentiated and directly activated
      GABAA receptors, yet was devoid of sedative-anesthetic effects in rats after
      intraperitoneal injection. Given the important implications of these findings for
      theories of anesthesia, the authors compared the effects of 4-iodopropofol with
      those of propofol using established in vivo and in vitro assays of both GABAA
      receptor-dependent and -independent anesthetic actions. METHODS: The effects of
      propofol and 4-iodopropofol were analyzed on heterologously expressed recombinant
      human GABAA alpha1beta2gamma2 receptors, evoked population spike amplitudes in
      rat hippocampal slices, and glutamate release from rat cerebrocortical
      synaptosomes in vitro. Anesthetic potency was determined by loss of righting
      reflex in Xenopus laevis tadpoles, in mice after intraperitoneal injection, and
      in rats after intravenous injection. RESULTS: Like propofol, 4-iodopropofol
      enhanced GABA-induced currents in recombinant GABAA receptors, inhibited synaptic
      transmission in rat hippocampal slices, and inhibited sodium channel-mediated
      glutamate release from synaptosomes, but with reduced potency. After
      intraperitoneal injection, 4-iodopropofol did not produce anesthesia in mice, but
      it was not detected in serum or brain. However, 4-iodopropofol did produce
      anesthesia in tadpoles (EC50 = 2.5 +/- 0.5 microM) and in rats after intravenous
      injection (ED50 = 49 +/- 6.2 mg/kg). CONCLUSIONS: Propofol and 4-iodopropofol
      produced similar actions on several previously identified cellular and molecular
      targets of general anesthetic action, and both compounds induced anesthesia in
      tadpoles and rats. The failure of 4-iodopropofol to induce anesthesia in rodents
      after intraperitoneal injection is attributed to a pharmacokinetic difference
      from propofol rather than to major pharmacodynamic differences.

PMID- 11465598
TI  - Isoflurane blocks synaptic plasticity in the mouse hippocampus.
AB  - BACKGROUND: The volatile anesthetic isoflurane depresses glutamatergic
      transmission. In this study, the authors investigated the effects of isoflurane
      on the induction of long-term potentiation (LTP) and long-term depression (LTD)
      in slices from the juvenile and adult mouse hippocampus. Both forms of synaptic
      plasticity involve the activation of glutamate receptors. METHODS: Field
      excitatory postsynaptic potentials and excitatory postsynaptic currents from
      neurons in the CA1 area were evoked by stimulation of the Schaffer collateral
      commissural pathway. Two independent synaptic inputs were stimulated. Clinically
      relevant concentrations (0.2-0.3 mM) of isoflurane were added to the perfusion
      solution. RESULTS: Field excitatory postsynaptic potentials from slices of
      juvenile and adult mice were depressed to 37.3 +/- 6.1% and 58.3 +/- 7.4%,
      respectively, and excitatory postsynaptic currents were reduced to 36.7 +/- 5.4%
      by isoflurane. A brief tetanic stimulation (100 Hz, 1 s) induced stable LTP of
      field excitatory postsynaptic potentials. In the presence of isoflurane,
      tetanization failed to induce LTP. The effect of isoflurane on LTP induction was
      reversible and could be prevented by antagonizing gamma-aminobutyric acid type A
      receptors (GABAA). Low-frequency stimulation (1 Hz/900 pulses) induced LTD. In
      the presence of isoflurane, low-frequency stimulation failed to induce LTD.
      CONCLUSIONS: The prevention of the isoflurane-induced depression of LTP by the
      GABAA antagonist picrotoxin suggests an involvement of GABAA receptors. An
      enhancement of the efficacy of GABA-mediated inhibitory synaptic transmission
      prevents the depolarization of the postsynaptic membrane during tetanus,
      necessary for the induction of use-dependent alteration of synaptic strength. An
      impairment of these processes may be a cause for the transient loss of recall and
      cognitive impairment after anesthesia in juvenile and adult brains.

PMID- 11465599
TI  - Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats.
AB  - BACKGROUND: The perioperative period is characterized by a state of
      immunosuppression, which was shown in animal studies to underlie the promotion of
      tumor metastasis by surgery. As this immunosuppression is partly ascribed to the
      neuroendocrine stress response, the authors hypothesized that spinal blockade,
      known to attenuate this response, may reduce the tumor-promoting effect of
      surgery. METHODS: Fischer-344 rats were subjected to a laparotomy during general
      halothane anesthesia alone or combined with either systemic morphine (10 mg/kg)
      or spinal block using bupivacaine (50 microg) with morphine (10 microg). Control
      groups were either anesthetized or undisturbed. Blood was drawn 5 h after surgery
      to assess number and activity of natural killer cells, or rats were inoculated
      intravenously with MADB106 adenocarcinoma cells, which metastasize only to the
      lungs. Metastatic development was assessed by quantifying lung retention of tumor
      cells 24 h after inoculation or by counting pulmonary metastases 3 weeks later.
      RESULTS: Laparotomy conducted during general anesthesia alone increased lung
      tumor retention up to 17-fold. The addition of spinal block reduced this effect
      by 70%. The number of metastases increased from 16.7 +/- 10.5 (mean +/- SD) in
      the control group to 37.2 +/- 24.4 after surgery and was reduced to 10.5 +/- 4.7
      during spinal block. Systemic morphine also reduced the effects of surgery, but
      to a lesser degree. Natural killer cell activity was suppressed to a similar
      extent by surgery and by anesthesia alone. CONCLUSIONS: The addition of spinal
      blockade to general halothane anesthesia markedly attenuates the promotion of
      metastasis by surgery.

PMID- 11465600
TI  - An obligatory role for spinal cholinergic neurons in the antiallodynic effects of
      clonidine after peripheral nerve injury.
AB  - BACKGROUND: Indirect evidence supports a role of spinal cholinergic neurons in
      tonically reducing response to noxious mechanical stimulation and in effecting
      analgesia from alpha2-adrenergic agonists. This study directly assessed the role
      of cholinergic neurons in regulating the level of mechanical allodynia and in
      participating in the antiallodynic effect of the clinically used alpha2
      adrenergic agonist, clonidine, in an animal model of neuropathic pain. METHODS:
      Allodynia was produced in rats by ligation of the left L5 and L6 spinal nerves.
      Rats received a single intrathecal injection of saline or one of three different
      doses of the cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64
      A; 2, 5, and 15 nmol). Seven days later, allodynia was assessed before and after
      intrathecal injection of 15 microg clonidine. The spinal cord was removed, and
      spinal cord acetylcholine content, cholinergic neuron number and distribution,
      and alpha2-adrenergic receptor expression were determined. RESULTS: AF64-A
      administration reduced both the number of cholinergic cells and the acetylcholine
      content of the lumbar dorsal spinal cord by 20-50% but did not affect level of
      mechanical allodynia. AF64-A did, however, completely block the anti-allodynic
      effect of clonidine. AF64-A did not reduce alpha2-adrenergic ligand binding in
      dorsal lumbar cord. CONCLUSIONS: These data suggest that spinal cholinergic tone
      does not affect the level of mechanical allodynia after peripheral nerve injury.
      There is a quantitative reliance on spinal cholinergic neurons in the allodynia
      relieving properties of intrathecal clonidine, and this reliance does not depend
      on alpha2-adrenergic receptors colocalized on spinal cholinergic interneurons.

PMID- 11465601
TI  - Signal transduction of opioid-induced cardioprotection in ischemia-reperfusion.
AB  - BACKGROUND: Morphine reduces myocardial ischemia-reperfusion injury in vivo and
      in vitro. The authors tried to determine the role of opioid delta1 receptors,
      oxygen radicals, and adenosine triphosphate-sensitive potassium (KATP) channels
      in mediating this effect. METHODS: Chick cardiomyocytes were studied in a flow
      through chamber while pH, flow rate, oxygen, and carbon dioxide tension were
      controlled. Cell viability was quantified by nuclear stain propidium iodide, and
      oxygen radicals were quantified using molecular probe 2',7'-dichlorofluorescin
      diacetate. RESULTS: Morphine (1 microM) or the selective delta-opioid receptor
      agonist BW373U86 (10 pM) given for 10 min before 1 h of ischemia and 3 h of
      reoxygenation reduced cell death (31 +/- 5%, n = 6, and 28 +/- 5%, n = 6 [P <
      0.05], respectively, 53 +/- 6%, n = 6, in controls) and generated oxygen radicals
      before ischemia (724 +/- 53, n = 8, and 742 +/- 75, n = 8 [P < 0.05],
      respectively, vs. 384 +/- 42, n = 6, in controls, arbitrary units). The
      protection of morphine was abolished by naloxone, or the selective delta1-opioid
      receptor antagonist 7-benzylidenenaltrexone. Reduction in cell death and increase
      in oxygen radicals with BW373U86 were blocked by the selective mitochondrial KATP
      channel antagonist 5-hydroxydecanoate or diethyldithiocarbamic acid (1,000
      microM), which inhibited conversion of O2- to H2O2. The increase in oxygen
      radicals was abolished by the mitochondrial electron transport inhibitor
      myxothiazoL Reduction in cell death was associated with attenuated oxidant stress
      at reperfusion. CONCLUSION: Stimulation of delta1-opioid receptors generates
      oxygen radicals via mitochondrial KATP channels. This signaling pathway
      attenuates oxidant stress and cell death in cardiomyocytes.

PMID- 11465602
TI  - Local anesthetic inhibition of voltage-activated potassium currents in rat dorsal
      root ganglion neurons.
AB  - BACKGROUND: Local anesthetic actions on the K+ channels of dorsal root ganglion
      (DRG) and dorsal horn neurons may modulate sensory blockade during neuraxial
      anesthesia. In dorsal horn neurons, local anesthetics are known to inhibit
      transient but not sustained K+ currents. The authors characterized the effects of
      local anesthetics on K+ currents of isolated DRG neurons. METHODS: The effects of
      lidocaine, bupivacaine, and tetracaine on K+ currents in isolated rat DRG neurons
      were measured with use of a whole cell patch clamp method. The currents measured
      were fast-inactivating transient current (I(Af)), slow-inactivating transient
      current (I(As)), and noninactivating sustained current (I(Kn)). RESULTS: One
      group of cells (type 1) expressed I(Af) and I(Kn). The other group (type 2)
      expressed I(As) and I(Kn). The diameter of type 2 cells was smaller than that of
      type 1 cells. Lidocaine and bupivacaine inhibited all three K+ currents.
      Tetracaine inhibited I(As) and I(Kn) but not I(Af) For bupivacaine, the
      concentration for half-maximal inhibition (IC50) of I(Kn) in type 2 cells was
      lower than that for I(Kn) in type 1 cells (57 vs. 121 microM). Similar results
      were obtained for tetracaine (0.6 vs. 1.9 mM) and for lidocaine (2.2 vs. 5.1 mM).
      CONCLUSIONS: Local anesthetics inhibited both transient and sustained K+ currents
      in DRG neurons. Because K+ current inhibition is known to potentiate local
      anesthetic-induced impulse inhibition, the lower IC50 for I(Kn) of small type 2
      cells may reflect preferential inhibition of impulses in nociceptive neurons. The
      overall modulatory actions of local anesthetics probably are determined by their
      differential effects on presynaptic (DRG) and postsynaptic (dorsal horn neurons)
      K+ currents.

PMID- 11465603
TI  - Propofol increases myofilament Ca2+ sensitivity and intracellular pH via
      activation of Na+-H+ exchange in rat ventricular myocytes.
AB  - BACKGROUND: The objectives were to determine the extent and mechanism of action
      by which propofol increases myofilament Ca2+ sensitivity and intracellular pH
      (pHi) in ventricular myocytes. METHODS: Freshly isolated adult rat ventricular
      myocytes were used for the study. Cardiac myofibrils were extracted for
      assessment of myofibrillar actomyosin adenosine triphosphatase (ATPase) activity.
      Myocyte shortening (video edge detection) and pHi (2',7'-bis-(2-carboxyethyl)
      5(6')-carboxyfluorescein, 500/440 ratio) were monitored simultaneously in
      individual cells field-stimulated (0.3 Hz) and superfused with HEPES-buffered
      solution (pH 7.4, 30 degrees C). RESULTS: Propofol (100 microM) reduced the Ca2+
      concentration required for activation of myofibrillar actomyosin ATPase from pCa
      5.7 +/- 0.01 to 6.6 +/- 0.01. Increasing pHi (7.05 +/- 0.03 to 7.39 +/- 0.04)
      with NH4Cl increased myocyte shortening by 35 +/- 12%. Washout of NH4Cl decreased
      pHi to 6.82 +/- 0.03 and decreased myocyte shortening to 52 +/- 10% of control.
      Propofol caused a dose-dependent increase in pHi but reduced myocyte shortening.
      The propofol-induced increase in pHi was attenuated, whereas the decrease in
      myocyte shortening was enhanced after pretreatment with ethylisopropyl amiloride,
      a Na+-H+ exchange inhibitor, or bisindolylmaleimide I, a protein kinase C
      inhibitor. Propofol also attenuated the NH4Cl-induced intracellular acidosis,
      increased the rate of recovery from acidosis, and attenuated the associated
      decrease in myocyte shortening. Propofol caused a leftward shift in the
      extracellular Ca2+-shortening relation, and this effect was attenuated by
      ethylisopropyl amiloride. CONCLUSIONS: These results suggest that propofol
      increases the sensitivity of myofibrillar actomyosin ATPase to Ca2+ (ie.,
      increases myofilament Ca2+ sensitivity), at least in part by increasing pHi via
      protein kinase C-dependent activation of Na+-H+ exchange.

PMID- 11465604
TI  - Sensory processing in the deep spinal dorsal horn of neurokinin-1 receptor
      knockout mice.
AB  - BACKGROUND: The neurokinin-1 receptor and its primary ligand, substance P, are
      widely recognized as contributing to the spinal processing of nociceptive
      stimuli, yet the specific function of the neurokinin-1 receptor remains unclear.
      METHODS: To better clarify these functions, the authors examined the
      neurophysiologic responses of L4-L5 neurons in the deep dorsal horn to acute
      mechanical, thermal, and electrical stimuli in knockout and wild-type mice. In
      addition, the capacity of knockout and wild-type mice to show wind-up to repeated
      C-fiber stimuli and to show sensitization after cutaneous mustard oil was
      assessed. RESULTS: A total of 68 nociceptive neurons (35 in knockout, 33 in wild
      type) in laminae III-V were studied. No differences in the acute responses of
      neurons in knockout and wild-type mice to graded mechanical, thermal, or
      electrical stimuli or in the acute responses to mustard oil were observed.
      However, wind-up to repeated electrical stimulation at C-fiber intensity was
      significantly attenuated in the knockout mice compared with wild type controls.
      In addition, mustard oil-induced mechanical hypersensitivity was significantly
      reduced in the knockout mice. CONCLUSIONS: These results indicate that neurokinin
      1 receptors do not play a significant role in the responses of nociceptive
      neurons in the deep spinal dorsal horn to acute noxious mechanical, thermal,
      electrical, or chemical stimuli. On the other hand, neurokinin-1 receptors are
      critical for the central hyperexcitability that is observed in these neurons with
      repeated C-fiber inputs and to the central sensitization induced by topical
      mustard oil application.

PMID- 11465605
TI  - Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell
      (SAD) mouse model.
AB  - BACKGROUND: The hallmark of sickle cell disease (SCD) is erythrocyte sickling
      during deoxygenation of the abnormal hemoglobin S (HbS). When HbS is
      deoxygenated, it aggregates into polymers, resulting in distortion of the
      erythrocyte structure, producing microvascular thrombosis and ischemia. The
      transgenic SAD mouse produces three types of human hemoglobin: S, Antilles, and D
      Punjab (HbSAD) and provides an animal model for SCD. We studied the effects of
      nitric oxide (NO) breathing at various doses and time regimens in the presence of
      severe hypoxia (6% oxygen) using the SAD mouse model. METHODS: Age- and sex
      matched control and SAD mice were exposed to 6% oxygen breathing in an
      environmental chamber and assessed for survival up to 1 h. Animals received
      different inhaled NO concentrations before and/or during hypoxia. Blood was
      obtained to evaluate the oxyhemoglobin dissociation curve and measure
      methemoglobinemia. RESULTS: Pretreatment by breathing NO at 20 ppm by volume in
      air for 30 min, and continuing to breathe 20 ppm NO during hypoxia resulted in
      improvement in survival rates in the SAD mouse (75%, n = 8) as compared with
      control SAD mice (11%, n = 9; P < 0.001). Pretreatment alone or breathing lower
      doses of NO were not protective. Changes in HbSAD oxygen affinity were not
      detected with NO breathing, and methemoglobin levels were low in all surviving
      mice. CONCLUSIONS: Breathing NO produced a rapid, protective effect to severe
      hypoxic stress in SAD mice. There appears to be a required loading period between
      NO breathing and its beneficial effect during hypoxic stress, possibly because of
      the total amount of NO delivered to SAD hemoglobin, blood cell components, and
      endothelium. NO breathing may be beneficial as a therapeutic intervention in SCD.

PMID- 11465606
TI  - Gene therapy for the management of pain: Part I: Methods and strategies.

PMID- 11465607
TI  - Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion
      injury.

PMID- 11465608
TI  - Continuous veno-venous hemofiltration for the immediate management of massive
      rhabdomyolysis after fulminant malignant hyperthermia in a bodybuilder.

PMID- 11465609
TI  - Intraventricular administration of morphine and clonidine.

PMID- 11465610
TI  - Intraoperative seizures in cardiac surgical patients undergoing deep hypothermic
      circulatory arrest monitored with EEG.

PMID- 11465611
TI  - Memory by subarachnoid regional anesthesia.

PMID- 11465612
TI  - Phantom limb sensation: a need for more elaborated studies.

PMID- 11465613
TI  - Acromegaly, the Mallampati, and difficult intubation.

PMID- 11465614
TI  - CSE in labor and hypoglycemia.

PMID- 11465615
TI  - Intubating laryngeal mask airway and muscle relaxants: never together?

PMID- 11465616
TI  - Lower respiratory tract (LRT) infection.

PMID- 11465617
TI  - LTA cannula can facilitate a difficult tracheal intubation.

PMID- 11465618
TI  - Is gene therapy in our future?

PMID- 11465619
TI  - Propofol alters the pharmacokinetics of alfentanil in healthy male volunteers.
AB  - BACKGROUND: The influence of propofol on the pharmacokinetics of alfentanil is
      poorly understood. The authors therefore studied the effect of a pseudo-steady
      state concentration of propofol on the pharmacokinetics of alfentanil. METHODS:
      The pharmacokinetics of alfentanil was studied on two occasions in eight male
      volunteers in a randomized crossover manner with a 3-week interval. While
      breathing 30% O2 in air, 12.5 microg/kg intravenous alfentanil was given in 2
      min, followed by 25 microg.kg(-1).h(-1) for 58 min (sessions A and B). During
      session B, a target controlled infusion of propofol (target concentration, 1.5
      microg/ml) was given from 10 min before the start until 6 h after termination of
      the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram,
      respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored.
      Venous blood samples for determination of the plasma alfentanil concentration
      were collected until 6 h after termination of the alfentanil infusion. Nonlinear
      mixed-effects population pharmacokinetic models examining the influence of
      propofol and mean arterial pressure were constructed. RESULTS: A three
      compartment model, including a lag time accounting for the venous blood sampling,
      adequately described the concentration-time curves of alfentanil Propofol
      decreased the elimination clearance of alfentanil by 15%, rapid distribution
      clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean
      arterial pressure and systemic vascular resistance were significantly lower in
      the presence of propofol. Scaling the pharmacokinetic parameters to the mean
      arterial pressure instead of propofol improved the model. CONCLUSIONS: Propofol
      alters the pharmacokinetics of alfentanil. Hemodynamic changes induced by
      propofol may have an important influence on the pharmacokinetics of alfentanil.

PMID- 11465620
TI  - The neurologic and adaptive capacity score is not a reliable method of newborn
      evaluation.
AB  - BACKGROUND: The Neurologic and Adaptive Capacity Score (NACS) is a multi-item
      scale that was published in 1982 to measure the effects of intrapartum drugs on
      the neonate. Although this scoring system has been widely used in obstetric
      anesthesia research, studies confirming its reliability have not been published.
      The purpose of this study was to assess the reliability of the NACS. METHODS: Two
      teams of observers were trained to perform the NACS on healthy, term neonates
      born in the vertex presentation. Two examinations were performed on each neonate
      within the first 2.5 h of life. Simultaneous (or "split-half") reliability was
      assessed using the alpha coefficient. Test-retest reliability was assessed using
      the intraclass correlation coefficient. The test was considered to be reliable if
      a was greater than 0.7 and the intraclass correlation coefficient was greater
      than 0.6. RESULTS: Two hundred babies were studied. The a was 0.47 and the
      intraclass correlation coefficient was 0.38 (95% confidence interval, 0.24-0.52).
      CONCLUSIONS: The NACS had poor reliability both on simultaneous testing and in
      the test-retest situation when used to evaluate term, healthy neonates. The
      authors suggest that other measures need to be developed to evaluate the effect
      of intrapartum drug administration in the neonate. Health measurement scales
      should undergo rigorous assessment for reliability and validity before they are
      used in clinical practice or for research purposes.

PMID- 11465621
TI  - The effect of sevoflurane and desflurane on upper airway reactivity.
AB  - BACKGROUND: Although bronchial reactivity can be assessed by changes in airway
      resistance, there is no well-accepted measure of upper airway reactivity during
      anesthesia. The authors used the stimulus of endotracheal tube cuff inflation and
      deflation to assess changes in airway reactivity in patients anesthetized with
      sevoflurane and desflurane. METHODS: Sixty-four patients classified as American
      Society of Anesthesiologists physical status I or II participated in this
      randomized, double-blind study. Patients were anesthetized with either
      sevoflurane or desflurane at 1.0 and 1.8 minimum alveolar concentration (MAC).
      The trachea was stimulated by inflating the endotracheal tube cuff. A blinded
      observer assessed the severity of patient response to the stimulus and changes in
      hemodynamic variables. The process was repeated at the second MAC treatment
      condition. RESULTS: At 1.0 MAC, patients anesthetized with desflurane had a more
      intense response and a greater likelihood of significant coughing and associated
      hemodynamic changes (both at P < 0.05). At 1.8 MAC, sevoflurane and desflurane
      both suppressed clinically significant responses to tracheal stimulation.
      Interrater reliability was excellent for this measure of upper airway reactivity
      (P < 0.001). CONCLUSIONS: The assessment of the cough response to tracheal
      stimulation by endotracheal tube cuff inflation is a reliable and clinically
      meaningful measure of upper airway reactivity. At 1.0 MAC, sevoflurane is
      superior to desflurane for suppressing moderate and severe responses to this
      stimulus.

PMID- 11465622
TI  - Comparison of the intubating laryngeal mask airway with the fiberoptic intubation
      in anticipated difficult airway management.
AB  - BACKGROUND: The intubating laryngeal mask airway (ILMA; Fastrach; Laryngeal Mask
      Company, Henley-on-Thames, UK) may provide an alternative technique to fiberoptic
      intubation (FIB) to facilitate the management of the anticipated difficult
      airway. The authors therefore compared the effectiveness of the ILMA with FIB in
      patients with anticipated difficult intubation. METHODS: One hundred patients,
      with at least one difficult intubation criteria (Mallampati class III or IV,
      thyromental distance < 65 mm, interincisor distance < 35 mm) were enrolled (FIB
      group, n = 49; ILMA group, n = 51) in this prospective randomized study.
      Anesthesia was induced with propofol and maintained with alfentanil and propofol
      after an efficient mask ventilation has been demonstrated. The success of the
      technique (within three attempts), the number of attempts, duration of the
      successful attempt, and adverse events (oxygen saturation < 90%, bleeding) were
      recorded. RESULTS: The rate of successful tracheal intubation with ILMA was 94%
      and comparable with FIB (92%). The number of attempts and the time to succeed
      were not significantly different between groups. In case of failure of the first
      technique, the alternative technique always succeeded. Failures in FIB group were
      related to oxygen desaturation (oxygen saturation < 90%) and bleeding, and to
      previous cervical radiotherapy in the ILMA group. Adverse events occurred
      significantly more frequently in FIB group than in ILMA group (18 vs. 0%, P <
      0.05). CONCLUSION: The authors obtained a high success rate and comparable
      duration of tracheal intubation with ILMA and FIB techniques. In patients with
      previous cervical radiotherapy, the use of ILMA cannot be recommended.
      Nevertheless, the use of the ILMA was associated with fewer adverse events.

PMID- 11465623
TI  - Subanesthetic isoflurane affects task-induced brain activation in a highly
      specific manner: a functional magnetic resonance imaging study.
AB  - BACKGROUND: Functional magnetic resonance imaging of blood oxygenation level
      dependent signal changes offers a very promising approach to investigate
      activated neural networks during anesthesia. METHODS: Sixteen healthy male
      volunteers, assigned into two groups of eight subjects (isoflurane group, control
      group), were investigated by functional magnetic resonance imaging during
      different experimental conditions. The isoflurane group successively breathed air
      (baseline condition), isoflurane in air (0.42 vol% inspiratory; isoflurane
      condition) and air again (recovery condition) while performing a visual search
      task, whereas the control group breathed air during all experimental conditions.
      Functional magnetic resonance images were acquired during the entire experimental
      session. In addition, reaction times and error rates were recorded. RESULTS: A
      significant isoflurane-related decrease (z > 3.1 corresponding to P < 0.001) in
      task-induced brain activation was found in three distinct cortical regions: the
      right anterio-superior insula (Talairach coordinates: x = 32, y = 22, z = 8) and
      the banks of the left and right intraparietal sulcus (Talairach coordinates: x = 
      34, y = -36, z = 32; x = 22, y = -60, z = 41, respectively). Subcortical
      structures (lateral geniculate nucleus) and the primary cortices (motor cortex,
      visual cortex) were not affected. All measured parameters indicated a nearly
      complete recovery of the affected networks within 5 min. CONCLUSIONS: Our
      findings indicate that subanesthetic isoflurane affected task-induced activation
      in specific neural networks rather than causing a global decrease in functional
      activation.

PMID- 11465624
TI  - Response surface modeling of alfentanil-sevoflurane interaction on
      cardiorespiratory control and bispectral index.
AB  - BACKGROUND: Respiratory depression is a serious side effect of anesthetics and
      opioids. The authors examined the influence of the combined administration of
      sevoflurane and alfentanil on ventilatory control, heart rate (HR), and
      Bispectral Index (BIS) in healthy volunteers. METHODS: Step decreases in end
      tidal partial pressure of oxygen from normoxia into hypoxia (approximately 50
      mmHg) at constant end-tidal partial pressure of carbon dioxide (approximately 48
      mmHg) were performed in nine male volunteers at various concentrations of
      alfentanil and sevoflurane, ranging from 0 to 50 ng/ml for alfentanil and from 0
      to 0.4 end-tidal concentration (ET%) for sevoflurane, and with various
      combinations of alfentanil and sevoflurane. The alfentanil-sevoflurane
      interactions on normoxic resting (hypercapnic) ventilation (Vi), HR, hypoxic Vi,
      and HR responses and BIS were assessed by construction of response surfaces that
      related alfentanil and sevoflurane to effect using a population analysis.
      RESULTS: Concentration-effect relations were linear for alfentanil and
      sevoflurane. Synergistic interactions were observed for resting Vi and resting
      HR. Depression of Vi by 25% occurred at 38 +/- 11 ng/ml alfentanil (population
      mean +/- SE) and at 0.7 +/- 0.4 ET% sevoflurane. One possibility for 25%
      reduction when alfentanil and sevoflurane are combined is 13.4 ng/ml alfentanil
      plus 0.12 ET% sevoflurane. Additive interactions were observed for hypoxic Vi and
      HR responses and BIS. Depression of the hypoxic Vi response by 25% occurred at 16
      +/- 1 ng/ml alfentanil and 0.14 +/- 0.05 ET% sevoflurane. The effect of
      sevoflurane on the BIS (25% reduction of BIS occurred at 0.45 +/- 0.08 ET%) was
      independent of the alfentanil concentration. CONCLUSIONS: Response surface
      modeling was used successfully to analyze the effect of interactions between two
      drugs on respiration. The combination of alfentanil and sevoflurane causes more
      depression of Vi and HR than does the summed effect of each drug administered
      separately. The effects of combining alfentanil and sevoflurane on hypoxic Vi and
      HR responses and BIS could be predicted from the separate dose-response curves.
      Over the dose range tested, the hypoxic response is more sensitive to the effects
      of anesthetics and opioids relative to resting ventilation.

PMID- 11465625
TI  - Decreased endotoxin immunity is associated with greater mortality and/or
      prolonged hospitalization after surgery.
AB  - BACKGROUND: Patients undergoing noncardiac surgery often develop postoperative
      morbidity, potentially attributable to endotoxemia and the systemic inflammatory
      response syndrome. Endogenous antibodies to endotoxin may confer protection from
      endotoxin-mediated toxicity. The authors sought to determine the association of
      preoperative antiendotoxin immunity and death or prolonged hospitalization in a
      broad population of general surgical patients undergoing major surgery. METHODS:
      To test the hypothesis that low preoperative serum antiendotoxin core antibody
      (EndoCAb) concentration is an independent predictor of adverse outcome after
      general surgery, 1,056 patients undergoing routine noncardiac surgery were
      enrolled into a prospective, blinded, cohort study. Immunoglobulin M EndoCAb,
      immunoglobulin G EndoCAb, total inmunoglobulin M, and immunoglobulin G
      concentrations were measured in serum obtained preoperatively. A physiologic risk
      score using the established POSSUM criteria was assigned preoperatively to each
      patient. The primary predefined composite end point (postoperative complication)
      was either in-hospital death or postoperative length of stay greater than 10
      days. Multivariate logistic regression was used to test the study hypothesis.
      RESULTS: Overall, postoperative complication occurred in 234 of the 1,056
      patients (22.1%). Lower immunoglobulin M EndoCAb concentration (P = 0.006)
      predicted increased risk of postoperative complication independent of POSSUM
      physiologic risk score (P < 0.001). In contrast, total immunoglobulin M and total
      immunoglobulin G concentrations did not predict adverse outcome. Complications
      involved multiple organ systems and were generally unrelated to the type or site
      of surgery, consistent with the systemic inflammatory response syndrome.
      CONCLUSIONS: Adverse outcome after routine noncardiac surgery is common and is
      predicted in part by low concentrations of EndoCAb. The authors' findings suggest
      that endotoxemia may be a cause of postoperative morbidity after routine
      noncardiac surgery.

PMID- 11465626
TI  - Recovery of intraoperative microbicidal and inflammatory functions of alveolar
      immune cells after a tobacco smoke-free period.
AB  - BACKGROUND: Tobacco smoking inhibits alveolar macrophage function, but cessation
      of smoking markedly reduces the risk of postoperative pulmonary complications.
      The authors therefore evaluated the effect of nonsmoking duration on both
      antimicrobial and inflammatory functions of alveolar macrophages during
      anesthesia and surgery. METHODS: The authors studied 15 patients who had never
      smoked, 15 current smokers, and 41 former smokers, all of whom underwent general
      anesthesia. Former smokers were further allocated to one of three groups
      depending on their smoke-free periods: 2 months (n = 13), 3-5 months (n = 13),
      and 6-12 months (n = 15). Alveolar immune cells were collected by bronchoalveolar
      lavage immediately after induction of anesthesia, at 2 and 4 h after induction of
      anesthesia, and at the end of surgery. Opsonized and nonopsonized phagocytosis
      were measured. Microbicidal activity was determined as the ability of the
      macrophages to kill Listeria monocytogenes directly. Finally, we determined the
      expression of proinflammatory cytokines, including interleukin 1beta, interleukin
      8, interferon gamma, and tumor necrosis factor alpha, and of antiinflammatory
      cytokines (interleukin 4 and 10) by semiquantitative polymerase chain reaction.
      RESULTS: Nonopsonized and opsonized phagocytosis and microbicidal activity of
      alveolar macrophages (antimicrobial functions) decreased 20-50%, and the
      expression of genes for all proinflammatory and antiinflammatory cytokines
      increased 3-30-fold over time in all groups. Starting 4 h after induction of
      anesthesia, the decreases in antimicrobial functions were 1.5-3 times greater in
      current and former smokers (2 months' abstinence) than in patients who had never
      smoked. Starting 4 h after anesthesia, the increase in expression of all
      cytokines, except interleukin 8, was twofold to fivefold less in current and
      former smokers (2-6 months' abstinence) than in patients who had never smoked.
      CONCLUSION: Our data suggest that former smokers may have a limited ability to
      mount effective pulmonary immune defenses for long as 6 months after stopping
      cigarette use.

PMID- 11465627
TI  - Psychotogenic properties of benzodiazepine receptor inverse agonists.
AB  - The neurochemical, behavioral, and cognitive effects of the benzodiazepine
      receptor partial inverse agonist beta-carboline FG 7142 (FG), a drug
      traditionally described as exhibiting 'anxiogenic' effects, are proposed to model
      core components of present theories of the neuronal mechanisms of schizophrenia.
      FG activates the mesolimbic dopaminergic system and, via increases in
      dopaminergic activity in the nucleus accumbens, disinhibits corticopetal
      cholinergic projections. The latter effect of FG is hypothesized to mediate the
      hyperattentional impairments that contribute to the development of psychotic
      cognition. Furthermore, the FG-induced abnormal overprocessing of conditioned
      stimuli and contexts provides an explanation of the 'anxiogenic' effects of FG.
      The FG-induced increases in the activity of cortical cholinergic inputs and the
      FG-induced cognitive impairments in rats and monkeys were demonstrated to be
      attenuated by the administration of typical and atypical antipsychotic drugs.
      Compared to the classic psychotogenic drugs amphetamine and phencyclidine, the
      effects of FG serve as an alternative psychotogenic manipulation in research
      focusing on the cortical and cognitive aspects of current theories of
      schizophrenia.

PMID- 11465628
TI  - Cross tolerance between anorectic action and induction of Fos-ir with
      dexfenfluramine and 5HT1B/2C agonists in rats.
AB  - RATIONALE: We have shown that the anorectic effect of dexfenfluramine (DFEN), an
      agent that acutely increases synaptic availability of serotonin (5-HT), shows
      complete tolerance after 2-3 prior applications when using acute feeding
      protocols and low dosages. It is unlikely this is due to either accumulative
      weight loss or presynaptic 5-HT depletion. In this study, we examined the
      possible contribution of 5-HT1B/2C receptors to behavioral tolerance by testing
      for cross tolerance between DFEN and the 5-HT1B/2C receptor agonists, m-chloro-
      and trifluoromethyl-substituted phenylpiperazines (mCPP and TFMPP). Additionally,
      we sought neuronal correlates of the behavioral changes by study of the induction
      of Fos-like immunoreactivity (ir) in discrete brain regions. METHODS: Sprague
      Dawley rats received two or three pre-injections, at 2-day intervals, of 2 mg/kg
      DFEN or vehicle. The rats were then food deprived for 24 h and, 30 min prior to a
      1-h feeding test, received a s.c. injection of either DFEN, TFMPP (1 mg/kg), or
      mCPP (2 mg/kg). Additional groups received mCPP preinjections and test injection
      of either DFEN or mCPP. Rats in Fos-ir studies received similar injection
      regimens but were not food deprived and were perfused 1.5 h after the test
      injection. RESULTS: DFEN-pretreated rats showed complete anorectic tolerance to
      DFEN, TFMPP, and mCPP. However, rats given this regimen of mCPP pretreatment were
      tolerant to neither mCPP nor DFEN. Fos-ir induced by DFEN in each brain region
      examined was either significantly reduced or abolished by prior DFEN injections.
      TFMPP induced less Fos-ir in these regions than DFEN and this was attenuated by
      prior DFEN. CONCLUSIONS: The behavioral data indicate that tolerance to DFEN
      anorexia is mediated partially or completely by functional subsensitivity at 5
      HT1B and/or 5-HT2C receptors. The brain regions implicated include the
      paraventricular hypothalamus, medial striatum, lateral parabrachial nucleus, and
      nucleus of the solitary tract.

PMID- 11465629
TI  - Preference for a cocaine-associated environment is attenuated by augmented
      accumbal serotonin in cocaine withdrawn rats.
AB  - RATIONALE: Recent studies have found decreased serotonin (5-HT) transmission
      within the nucleus accumbens following withdrawal from chronic cocaine.
      OBJECTIVE: We sought to investigate whether increasing brain 5-HT levels would
      decrease behavioral responses that occur following cocaine withdrawal, namely
      increased preference for a cocaine environment and anxiety. METHODS: The
      conditioned place preference and the defensive burying paradigms were used to
      measure the behavioral responses that occur 1 week following cocaine withdrawal.
      RESULTS: We show that pharmacological agents that increase 5-HT transmission
      (sertraline or 5-hydoxytryptophan, 5-HTP) abolish the preference of
      subchronically cocaine-treated, abstinent rats for a cocaine-associated
      environment. Similar results were seen when sertraline was microinjected into the
      nucleus accumbens. Conversely, rats acutely conditioned with cocaine showed an
      increased preference for a cocaine-associated environment when pretreated with
      these drugs. Sertraline also decreased the heightened anxiety-like behaviors
      found in subchronically treated cocaine rats. CONCLUSIONS: These results indicate
      that drugs that augment 5-HT function may reduce the desire for cocaine following
      cocaine withdrawal, and thus facilitate cocaine abstinence in dependent subjects.

PMID- 11465630
TI  - Cocaine and salicylate: documentation of hydroxyl radical formation in hearts and
      brains of 18-day-old chick embryos and unexpected interactive toxicity.
AB  - RATIONALE: Multiple low doses of cocaine (COC) may cause intermittent
      vasoconstriction and reperfusion, leading to elevations in damaging reactive
      oxygen species, such as hydroxyl free radicals (*OH). Salicylate may offer
      protection because it reacts with *OH and/or because of its anti-inflammatory
      actions. OBJECTIVE: To measure *OH concentrations in hearts and brains of chicken
      embryos exposed to multiple, small doses of COC, and to determine if otherwise
      non-toxic doses of sodium salicylate (NaSal) protected against the marginal but
      significant reduction in hatchability caused by a model of "binge" COC exposure.
      METHODS: Three experiments were carried out. In the first, 67.5 mg COC/kg egg was
      administered as five doses of 13.5 mg/kg egg or 0.675 mg/egg every 1.5 h,
      injected just beneath the shell, on day 18 of development (E18), 1 h after NaSal
      (25 or 100 mg/kg egg) was injected as a bolus. Hearts and brains taken shortly
      afterward were analyzed for *OH. In experiment 2, the dose of COC was reduced to
      56.5 mg/kg egg so as to achieve a small but significant reduction in hatchability
      in order to determine if NaSal protected against or enhanced COC's toxicity,
      manifest as an increase or decrease in hatchability. The doses of NaSal for this
      experiment were 50, 100 or 200 mg/kg egg, all devoid of effects upon hatchability
      when injected alone. Experiment 3 was done to confirm the presence of vascular
      disruptions/hemorrhages observed on COC-exposed embryos while harvesting hearts
      and brains for chemical analyses and to quantify what appeared to be enhanced COC
      related vascular accidents associated with NaSal pretreatment. The dose of NaSal
      used in experiment 3 was 200 mg/kg egg and COC was injected again at 5x13.5 mg/kg
      egg. RESULTS: COC increased *OH in hearts and brains of chicken embryos on E18,
      and non-toxic doses of NaSal (i.e. 100 or 200 mg/kg egg) enhanced COC's toxicity
      in a dose-related manner. The lowest NaSal dose (50 mg/kg egg) may have offered
      some protection against the effects of COC, as the reduction in hatchability
      caused by 56.5 mg COC/kg egg was no longer significant. Vascular
      disruptions/hemorrhages were associated with and most likely responsible for the
      interactive toxicity. CONCLUSIONS: Our unexpected findings may be of clinical
      relevance because of the use of aspirin for treatment of misdiagnosed
      "preeclamptic" COC-abusing pregnant women and its possible use for COC abusers at
      risk for reduced cerebral blood flow and stroke.

PMID- 11465631
TI  - Substantia nigra pars reticulata is a highly potent site of action for the
      behavioral effects of the D1 antagonist SCH 23390 in the rat.
AB  - RATIONALE: Considerable evidence indicates that dopaminergic drugs, including
      drugs that act on D1 receptors, exert their effects by actions on forebrain
      dopamine terminal regions. Nevertheless, anatomical studies also have
      demonstrated that there is a high concentration of D1 receptors in the substantia
      nigra pars reticulata (SNr). The D1 receptors in SNr are located largely on the
      terminals of gamma-aminobutyric acid (GABA)-ergic striatonigral neurons. The
      present studies were undertaken to determine whether the D1 antagonist SCH 23390
      was effective if locally injected into SNr and to compare the results of SNr
      injections with those obtained from other brain sites. Fixed ratio 5 (FR5) lever
      pressing and open-field locomotion were used as the behavioral tests because
      these tasks are sensitive to systemic SCH 23390. METHODS: Rats received bilateral
      implantations of guide cannulae into either nucleus accumbens, neostriatum, SNr,
      or control sites in the cortex or brainstem. Rats in the FR5 study were trained
      prior to surgery. All rats received one of the following local injections (0.5
      microl per side): vehicle, 0.25, 0.5, 1.0, or 2.0 microg SCH 23390. RESULTS: In
      the FR5 study, the SNr was by far the most potent site for suppression of lever
      pressing, with an ED50 (dose that produces half maximal response) of 0.33 microg
      per side. Nucleus accumbens and neostriatum injections were less potent than
      those in SNr, but more potent than injections into the control regions. With open
      field locomotion, the SNr, nucleus accumbens, and neostriatum were approximately
      equipotent sites, and all three were more potent than the control sites.
      CONCLUSIONS: SNr was a very potent site for suppression of lever pressing and
      open-field locomotion. These data suggest that D1 antagonists have multiple sites
      of action, including not only the forebrain dopamine terminal regions but also
      the SNr. It is possible that blockade of SNr D1 receptors modulates GABA release
      from striatonigral neurons.

PMID- 11465632
TI  - Short-term contextual sensitisation and conditioned hyperkinesia produced by
      cocaine in suckling rats aged 4-10 days and 14-20 days.
AB  - RATIONALE: It was hypothesised that the failure to generate sensitisation to the
      behavioural effects of a motor stimulant in suckling rats was mainly due to not
      pairing the drug with the test context during chronic pretreatment. OBJECTIVE:
      This study probed the capabilities of neonatal and infant rat pups to show short
      term context-specific sensitisation and conditioned drug activity produced by
      cocaine. METHODS: Two similar experiments were conducted on rat pups aged 4-10
      days or 14-20 days, each experiment comprising three phases: a sensitisation
      phase (days 4-8 and days 14-18 of age), a test session under cocaine for context
      specificity of sensitisation (day 9 and day 19 of age) and a test session under
      saline for conditioned drug effects (day 10 and day 20 of age). Over five daily
      sessions, pups first received an injection of either 16 mg/kg cocaine (paired
      group) or saline (unpaired group) in test chambers, and 110 min later the
      converse injections in the vivarium (in a cage that was different from the home
      cage). A third group received saline in both contexts. Behaviour was scored using
      videotapes. RESULTS: Sensitisation developed in the paired groups at both ages.
      In 4- to 10-day-old pups, sensitisation was expressed via locomotion (matrix
      crosses) and also horizontal and vertical activities (categories comprising
      several age-specific movements). In 14- to 18-day-old pups, it was displayed by
      increases in head movements and vertical activity, and by a decline in stationary
      position. These effects were confirmed to be context specific on the test
      sessions (day 9 or day 19), the paired groups producing by far the greatest
      values. On the conditioning test, the paired groups also produced the greatest
      amounts of the above-mentioned behaviours, revealing a conditioned drug effect.
      Additionally, the conditioned effect scores were higher than those of two
      additional groups that had been treated similarly to the others but outside the
      chamber until the two tests (controlling for a withdrawal effect and possible
      novelty-induced activity in the test context). There were no differences between
      these unexposed groups, indicating that no abstinence effect occurred.
      CONCLUSIONS: The results demonstrate that neonatal rats are capable of showing
      physiological/non-contextual cocaine-induced behavioural sensitisation as well as
      its context-specific expression and the conditioned activity following its
      establishment.

PMID- 11465633
TI  - Higher occupancy of muscarinic receptors by olanzapine than risperidone in
      patients with schizophrenia. A[123I]-IDEX SPECT study.
AB  - RATIONALE: In vitro data have shown anticholinergic properties of the atypical
      antipsychotic drug olanzapine. Substantial occupancy of muscarinic receptors may
      be an explanation for the low incidence of extrapyramidal side effects induced by
      olanzapine. OBJECTIVES: To obtain an in vivo measurement of muscarinic receptor
      occupancy by olanzapine compared with risperidone in patients with schizophrenia
      stabilised on medication. METHODS: Five patients with schizophrenia treated with
      olanzapine and five patients treated with risperidone were studied. Muscarinic
      receptor occupancy in the striatum and cortex was studied in vivo with SPECT
      using [123I]-IDEX as a radioligand. SPECT data were compared with those of six
      healthy subjects. RESULTS: Patients stabilised on olanzapine showed significantly
      lower mean (+/-SD) striatal and cortical (1.50+/-0.21 and 1.51+/-0.22,
      respectively) muscarinic receptor binding ratios of [123I]-IDEX (reflecting
      higher levels of muscarinic receptor occupancy) than controls (3.91+/-0.61 and
      3.65+/-0.70, respectively). Furthermore, [123I]-IDEX binding ratios in patients
      treated with risperidone were slightly lower than controls, reaching significance
      only in the striatum (2.99+/-0.27 versus 3.91+/-0.61, for risperidone and
      controls). CONCLUSIONS: The substantial occupancy of muscarinic receptors in the
      striatum and cortex by olanzapine may be an explanation for the low incidence and
      severity of extrapyramidal side effects of this antipsychotic drug. Furthermore,
      it may also explain the anticholinergic side effects of olanzapine.

PMID- 11465634
TI  - The "selective" dopamine D1 receptor antagonist, SCH23390, is a potent and high
      efficacy agonist at cloned human serotonin2C receptors.
AB  - RATIONALE: The benzazepine and "selective" dopamine D1 receptor antagonist,
      SCH23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7
      ol], shows significant affinity at native serotonin (5-HT)2C receptors.
      OBJECTIVES: We examined its functional actions at cloned human (h)5-HT2C
      receptors (VSV isoform) stably expressed in CHO cells. METHODS: Since 5-HT2C
      receptors are positively coupled to phospholipase C (PLC), their activation was
      determined by depletion of membrane-bound pools of pre-labelled
      [3H]phosphotidylinositol ([3H]PI). RESULTS: SCH23390 showed high affinity (Ki,
      9.3 nM) at h5-HT2C sites and depleted [3H]PI with an EC50 of 2.6 nM. Its efficacy
      was equivalent to that of 5-HT. [3H]PI depletion elicited by SCH23390 was
      concentration-dependently abolished by the selective 5-HT2C antagonist,
      SB242,084, with a K(B) of 0.55 nM. Further, in the presence of a fixed
      concentration of SB242,084 (10 nM), the concentration-response curve for SCH23390
      was shifted to the right without loss of maximal effect, yielding a K(B) of 0.57
      nM. CONCLUSIONS: SCH23390 is a potent and high efficacy agonist at h5-HT2C
      receptors. Activation of 5-HT2C receptors by SCH23390 may contribute to its
      functional properties both in animals and in humans.

PMID- 11465635
TI  - Reinforcement by orally delivered methadone, cocaine, and methadone-cocaine
      combinations in rhesus monkeys: are the combinations better reinforcers?
AB  - RATIONALE: Polydrug abuse is a problem that has been infrequently examined. In
      the present study, drug self-administration procedures were used to investigate
      the reinforcing effects of drug combinations. OBJECTIVES: To determine the
      absolute and relative response rates maintained by orally delivered methadone,
      cocaine, and their combinations under sequential and concurrent access. Choice
      between drug combinations containing different concentrations of cocaine was also
      determined. METHODS: Oral intake of methadone, cocaine, and their combinations
      was studied with rhesus monkeys during daily 3-h sessions. Lip contact (the
      operant response) was reinforced by delivery of liquid contingent upon completion
      of a fixed-ratio schedule. In one series, the drugs and drug combinations were
      studied sequentially with the water vehicle concurrently available. In the next
      series, the drugs and drug combinations were concurrently available. In the third
      series, pairs of drug combinations containing different concentrations of cocaine
      were also concurrently available. RESULTS: Methadone, cocaine and their
      combinations functioned as reinforcers. Under sequential access, response rates
      for the drug combinations and the component drugs were often similar. However,
      under concurrent access, response rates for the drug combinations were greater
      than response rates for the component drugs at the highest FR size for each
      condition. Also, drug combinations containing higher cocaine concentrations were
      preferred to combinations containing lower cocaine concentrations. CONCLUSIONS:
      Combinations of methadone and cocaine have relatively greater reinforcing effects
      than the component drugs, and these greater reinforcing effects are better
      detected with concurrent measures than with sequential measures.

PMID- 11465636
TI  - Reduction in basal afternoon plasma ACTH during early treatment of depression
      with fluoxetine.
AB  - RATIONALE: Subjects with depression may exhibit activation of the hypothalamic
      pituitary-adrenal (HPA) axis, but little is known about the response of basal
      hormone levels to antidepressant therapy. OBJECTIVES: To determine whether
      treatment of depression with standard antidepressant medications resulted in
      reductions in basal activity of afternoon cortisol, ACTH and AVP. A secondary aim
      was to examine whether there was any difference in hormonal response between an
      SSRI (fluoxetine) and a tricyclic antidepressant (nortriptyline). METHODS: Forty
      three subjects with a DSM-IV diagnosis of depression (Hamilton score 18.9+/-0.6
      at baseline) had five basal venous blood samples drawn at 15-min intervals
      between 1400 and 1500 hours for cortisol, ACTH and AVP, before and 6 weeks after
      randomisation to treatment with fluoxetine (n=27) or nortriptyline (n=16).
      RESULTS: Both medications resulted in a similar improvement in depression as
      determined by Hamilton score. In the group as a whole, ACTH levels showed a
      significant decrease over the 6 weeks (4.1+/-0.4 pmol/l at baseline versus 3.3+/
      0.3 at 6 weeks, P<0.05), while cortisol and AVP levels were unchanged. Further
      analysis revealed that the fall in plasma ACTH occurred predominantly in the
      subgroup treated with fluoxetine (drug x time interaction by ANOVA, P=0.035).
      There was a significant relationship between cortisol and ACTH at baseline
      (r=0.48, P=0.002), that weakened considerably after treatment (r=0.22, P=0.16).
      The subgroup with baseline hypercortisolemia [mean cortisol >276 nmol/l (10
      microg/dl), n=18] demonstrated a reduction in both cortisol and ACTH following
      treatment, but also showed a loss of the relationship between the two.
      CONCLUSIONS: It is postulated that the initial recovery of the HPA axis during
      the treatment of depression with fluoxetine is mediated via restoration of
      glucocorticoid negative feedback on ACTH levels.

PMID- 11465637
TI  - Cannabinoid receptor agonist and antagonist effects on motor function in normal
      and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human
      primates.
AB  - RATIONALE: Although cannabinoid effects on motor function have been extensively
      studied in rodents, the role of cannabinoids in regulating behavior in primates
      is relatively unknown. OBJECTIVES: We compared the effects of cannabinoid
      agonists and dopamine antagonists on unconditioned behaviors in cynomolgus
      monkeys (Macaca fascicularis). We further investigated the therapeutic potential
      of cannabinoid antagonists in a primate model of Parkinson's disease. METHODS:
      Drugs were administered i.m., and sessions were videotaped and rated by a "blind"
      observer using a rating scale. RESULTS: The dopamine antagonist haloperidol
      decreased locomotor activity and increased bradykinesia in three subjects.
      Haloperidol also produced a dose-dependent increase in freezing and catalepsy in
      two out of the three subjects. The cannabinoid agonist levonantradol dose
      dependently decreased general and locomotor activity and increased bradykinesia.
      In contrast to haloperidol, levonantradol failed to produce freezing or
      catalepsy. At the dose range studied, tetrahydrocannabinol did not affect general
      or locomotor activity, but increased bradykinesia. In view of the psychomotor
      slowing induced by cannabinoid agonists, we investigated the therapeutic
      potential of the cannabinoid receptor antagonist SR141716A in an early and
      advanced stage of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine-induced
      parkinsonism. In both models of Parkinson's disease, SR141716A failed to
      alleviate the motor deficits of parkinsonism. CONCLUSIONS: Cannabinoid agonists
      do not induce catalepsy in primates, a finding that differs from their effects in
      rodents. The primate may be more suitable than rodents for predicting the effects
      of cannabinoids and their therapeutic potential on select primate behaviors.

PMID- 11465638
TI  - Effects of moclobemide on sexual performance and nocturnal erections in
      psychogenic erectile dysfunction.
AB  - RATIONALE AND OBJECTIVES: We tested the hypothesis that the selective reversible
      MAO-A inhibitor moclobemide has a specific therapeutic effect on erectile
      dysfunction independent of its antidepressive properties. METHODS: In a double
      blind placebo controlled study, 12 male outpatients suffering from psychogenic
      erectile dysfunction without any other psychiatric disorder were investigated.
      Based on comprehensive diagnosis before the beginning of the study, organic
      factors relevant for sexual function were excluded. The treatment period was 8
      weeks. Half the patients received 450 mg moclobemide during the first week, and
      600 mg afterwards; the others received placebo. Apart from assessment of erectile
      function by means of the Clinical Global Impression (CGI) scale, nocturnal
      erections were measured under polysomnographic control at baseline and at the end
      of the treatment period. RESULTS: The evaluation of the CGI scale revealed a
      clearly stronger improvement under moclobemide compared to placebo during the
      study period. The therapeutic efficacy found on the subjective level had no clear
      correlate on the neurophysiological level. No alterations of nocturnal erectile
      parameters were obvious under treatment, neither were clinically relevant
      alterations found regarding sleep EEG parameters. The medication was well
      tolerated without serious adverse events. CONCLUSIONS: The findings support the
      hypothesis that moclobemide has a specific effect on erectile dysfunction. Thus,
      patients suffering from psychogenic erectile dysfunction who are not depressed
      might benefit from moclobemide without relevant side effects.

PMID- 11465639
TI  - Contextual control over the expression of fear in rats conditioned under a
      benzodiazepine.
AB  - RATIONALE: Benzodiazepines disrupt fear conditioning, but this disruption is
      context-specific; if rats have been conditioned under a benzodiazepine, their
      fear is recovered if they are tested in a different context. The present
      experiments investigated how the conditioning context controls fear in rats
      conditioned under a benzodiazepine. OBJECTIVES: The experiments had three aims:
      (1) to replicate the finding that fear is recovered when rats are tested in a
      different context, (2) to test whether the conditioning context reduces fear
      generally or only for the specific stimulus conditioned in that context and (3)
      to test whether latent inhibition of the conditioning context reduces its control
      over fear. METHODS: Rats were injected with the benzodiazepine midazolam (1.25
      mg/kg) or saline and exposed to a conditioned stimulus (CS) and shock in a
      distinctive chamber. Latent inhibition of the chamber was induced by extensively
      preexposing the rats to the chamber. The day after conditioning, fear was
      assessed by presenting the CS while rats were in either the conditioning chamber
      or a different chamber. RESULTS: The midazolam-induced reduction of fear was
      reversed (i.e. fear was partially recovered) if rats were tested in the different
      context, and was completely prevented if the conditioning context had been
      latently inhibited. These two effects were not additive since, when the
      conditioning context had been latently inhibited, rats showed less fear in the
      different context than in the conditioning context. CONCLUSIONS: We argue that
      midazolam does not disrupt conditioning, but imbues the conditioning context with
      control over retrieval of the CS-shock association. In this regard, the effects
      of midazolam closely parallel those of extinction.

PMID- 11465640
TI  - Time-dependent changes in extinction behavior and stress-induced reinstatement of
      drug seeking following withdrawal from heroin in rats.
AB  - RATIONALE AND OBJECTIVES: Footshock stress reliably reinstates heroin seeking in
      rats, but the time course of the development of this effect following drug
      withdrawal is not known. Here we studied the effect of intermittent footshock
      stress on reinstatement of heroin seeking following different withdrawal periods
      (1-66 days). We also studied whether changes in corticotropin-releasing factor
      (CRF) mRNA in the central nucleus of the amygdala (CeA) and the bed nucleus of
      the stria terminalis (BNST) are correlated with this reinstatement after 1 day
      and 6 days of heroin withdrawal. METHODS: Rats were trained to self-administer
      heroin (9 h/day; 0.1 mg/kg per infusion) for 10 days. Tests for extinction
      behavior and footshock-induced reinstatement of heroin seeking were then
      conducted after 1, 6, 12, 25, or 66 days of heroin withdrawal. On the test day,
      rats were given five to ten 60-min extinction sessions until they reached the
      extinction criterion of less than 15 responses per 60 min on the lever previously
      associated with heroin. Rats were then exposed to intermittent foot-shock (0.8
      mA; 10 min), and lever-pressing behavior was recorded for 120 min. RESULTS:
      Reinstatement of lever-pressing behavior by footshock followed an inverted U
      shaped curve with maximal responding after 6 days and 12 days of heroin
      withdrawal. Surprisingly, foot-shock did not reinstate lever-pressing behavior on
      day 1 of withdrawal. Lever pressing during extinction, prior to exposure to
      footshock, also followed an inverted U-shaped curve, with higher responding after
      6, 12, and 25 days of heroin withdrawal. Finally, compared with control groups
      not exposed to shock, CRF mRNA levels in response to footshock were increased in
      the CeA (day 1 of withdrawal) and the dorsal BNST (day 1 and day 6), but not in
      the ventral BNST. CONCLUSIONS: The duration of the heroin withdrawal period is an
      important factor in the manifestation of (1) footshock stress-induced
      reinstatement of heroin seeking and (2) extinction of the heroin-reinforced
      behavior. Finally, the time-dependent changes in footshock stress-induced
      reinstatement following withdrawal from heroin were not correlated with
      alterations in CRF mRNA in the CeA and BNST.

PMID- 11465641
TI  - Laragh's lessons in pathophysiology and clinical pearls for treating
      hypertension.

PMID- 11465642
TI  - Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers.
AB  - Smoking potentiates the enhanced cardiovascular risk of hypertensive patients.
      Although nicotine replacement therapy is safe when used by healthy individuals to
      quit smoking, there is no evidence that nicotine replacement therapy is safe in
      hypertensive smokers. In this crossover, single-blinded, placebo-controlled
      study, we compared for 4 h the acute effects of transdermal nicotine on the mean
      arterial pressure (MAP) and heart rate (HR) of mildly hypertensive smokers
      treated with hydrochlorothiazide with the responses in normotensive smokers and
      nonsmokers monitored with Finapres and ambulatory blood pressure systems. The
      plasma concentrations of thromboxane B2 (TXB2, the stable breakdown product of
      TXA2) were also measured by ELISA to assess whether transdermal nicotine acutely
      affects TXA2 production. The use of 21-mg nicotine patches increased the MAP and
      HR in nonsmokers (from 94+/-4 mm Hg and 69+/-3 beats/min to 117+/-7 mm Hg and
      83+/-3 beats/min, respectively; P < .05) as well as the MAP in normotensive
      smokers (from 83+/-4 to 106+/-7 mm Hg; P < .05). However, MAP and HR remained
      unaltered in hypertensive smokers after transdermal nicotine. Higher basal TXB2
      levels were observed in hypertensive smokers compared with normotensive smokers
      and nonsmokers (2019+/-402 v 670+/-167 and 556+/-68 pg/mL, respectively; P <
      .05). Transdermal nicotine increased the TXB2 levels only in nonsmokers (P <
      .05). These data indicate that the use of transdermal nicotine in mildly
      hypertensive smokers is probably safe. Further studies involving other classes of
      hypertensive patients are warranted.

PMID- 11465643
TI  - Does leptin cause functional peripheral sympatholysis?
AB  - Leptin is a protein produced by adipocytes. Leptin is known to markedly and
      rapidly increase sympathetic nerve activity to the kidney and hindlimb of
      experimental animals. Recent studies suggest that leptin may stimulate
      endothelial production of nitric oxide, which could oppose sympathetically
      induced vasoconstriction. We tested the hypothesis that such actions of leptin
      may produce peripheral functional sympatholysis. In Sprague-Dawley rats, we
      intermittently stimulated the abdominal sympathetic trunk and measured renal and
      hindlimb blood flows before and after 3 h of infusion of leptin (1000 microg/kg,
      n = 7) or vehicle (n = 7). Leptin did not change arterial pressure, heart rate,
      or renal or hindlimb conductance over the course of 3 h. In addition, leptin did
      not significantly alter sympathetically mediated vasomotor responses to
      electrical stimulation, as compared with vehicle. Thus, we conclude that leptin
      does not change regional blood flows, and that leptin also does not appear to
      have vascular or neural actions to cause peripheral functional sympatholysis.

PMID- 11465644
TI  - Leptin and norepinephrine plasma concentrations during glucose loading in
      normotensive and hypertensive obese women.
AB  - We performed this study to investigate whether changes in plasma glucose,
      insulin, and norepinephrine concentrations during an oral glucose tolerance test
      (OGTT) are associated with changes in plasma leptin levels in normotensive and
      hypertensive obese women. Plasma insulin, glucose, norepinephrine, and leptin
      concentrations were evaluated at the baseline and during OGTT in normotensive
      women (NT-Ob, N = 24, mean age 38.3+/-1.8 years, body mass index [BMI] 37.9+/-1.1
      kg/m2) and hypertensive (HT-Ob, N = 25, mean age 37.7+/-1.9 years, BMI 39.4+/-1.3
      kg/m2) obese women, and in a group of normal-weight women (controls, N = 20, mean
      age 38.3+/-1.3 years, BMI 23.1+/-0.4 kg/m2). The OGTT caused a significant
      increase in plasma leptin concentrations in both NT-Ob and HT-Ob groups, whereas
      no such change was detectable in control subjects. Area under curve (AUC) for
      plasma leptin showed a direct correlation with norepinephrine AUC in both NT-Ob
      (r = 0.73, P = .001) and HT-Ob (r = 0.74, P = .001) group, which was still
      detectable in multivariate analysis (P = .014 and P = .017, respectively). Our
      study confirms that glucose loading increases circulating leptin concentrations
      in obese women, and demonstrates the existance of an association between leptin
      and norepinephrine changes during OGTT in both normotensive and hypertensive
      obese women. We hypothesize that this association may reflect the lack of leptin
      suppression by catecholamines or a direct leptin-induced sympathoactivation.
      These findings suggest that leptin could be relevant in the regulation of blood
      pressure in obese women.

PMID- 11465645
TI  - A pilot study of homocyst(e)ine levels in essential hypertension: relationship to
      von Willebrand factor, an index of endothelial damage.
AB  - An interaction between homocyst(e)ine and the endothelium in hypertensive
      patients may promote thrombogenesis and atherogenesis, leading to adverse
      cardiovascular events. We hypothesized that homocyst(e)ine levels are abnormal in
      patients with essential hypertension, and that this may be related to an adverse
      effect on the vascular endothelium. Accordingly, we compared plasma levels of
      homocyst(e)ine and von Willebrand factor (marking endothelial damage) in 83
      patients (43 men; mean age 54 +/- standard deviation 15.9 years) with essential
      hypertension (> 160/90 mm Hg), with levels in 25 healthy normotensive controls
      (13 men; mean age 56+/-11.8 years). Baseline levels of the markers and other
      clinical indices were then related to adverse cardiovascular events at follow-up.
      Plasma homocyst(e)ine (P = .0001) and von Willebrand factor (P = .031) levels
      were significantly higher in hypertensives compared to controls. After a mean
      follow-up of 76 patients for 45 months (range, 1 to 66 months), 17 subjects
      experienced an end point of either cardiovascular death (n = 10) or adverse
      cardiovascular event (n = 7). Comparing these 17 with the 59 free of an end
      point, the former were older (P = .0002) and had a longer duration of known
      hypertension (P = .018). There was a nonsignificant trend toward higher median
      plasma homocyst(e)ine levels in the patients sustaining a vascular end point (P =
      .07). In this pilot study, we suggest that essential hypertension may be
      associated with increased plasma homocyst(e)ine levels, but that this amino acid
      is unrelated to endothelial damage (von Willebrand factor), clinical indices, or
      prognosis.

PMID- 11465646
TI  - Association of specific HLA phenotypes with left ventricular mass and carotid
      intima-media thickness in hypertensives.
AB  - The aim of this study was to investigate the hypothesis that the expression of
      certain HLA antigens may constitute a risk marker for cardiovascular hypertrophy
      in subjects with arterial hypertension. We examined 158 subjects with newly
      diagnosed arterial hypertension. HLA class I (-A, -B, -Cw) and class II (-DR, 
      DQ) antigens were studied by two-step microlymphocytotoxic technique in
      peripheral T and B lymphocytes. Carotid intima-media thickness (IMT) was
      determined noninvasively by ultrasonography. The left ventricular mass was
      calculated according to the formula of Devereux and was normalized by the
      individual's height (LVM/h). The individuals with DR13 and DR17 were
      characterized by higher values of IMT compared to those without these HLA
      (0.096+/-0.018 cm v 0.085+/-0.021 cm, P = .011, 0.100+/-0.019 cm v 0.084+/-0.021
      cm, P = .012, respectively). The presence of HLA DQ7 was characterized by
      markedly higher values of IMT that just failed to reach statistical significance
      (0.091+/-0.019 cm v 0.084+/-0.022 cm, P = .045). Furthermore, subjects with HLA
      DQ7 and DR11 exhibited higher values of LVM/h in comparison to those without
      these HLA (191.3+/-36.2 g/m v 166.9+/-41.0 g/m, P = .029 and 194.6+/-34.3 g/m v
      166.6+/-40.9 g/m, P = .034, respectively). Hypertensive subjects with HLA B51
      tended to have lower LVM/h (166.6+/-39.0 g/m with v 176.0+/-41.7 g/m without HLA
      B51, P = .045). In conclusion, it can be postulated that certain HLA phenotypes
      exhibit an association with increased carotid IMT and left ventricular mass in
      hypertensive subjects. The determination of these antigens may help to identify
      subjects at high risk for cardiovascular events.

PMID- 11465647
TI  - Effects of drug therapy on cardiac arrhythmias and ischemia in hypertensives with
      LVH.
AB  - Left ventricular hypertrophy (LVH) in hypertensive subjects is associated with an
      increased prevalence of ventricular arrhythmias. To evaluate the effect of
      antihypertensive treatment on cardiac arrhythmias (CA) and transient episodes of
      myocardial ischemia (TEMI), we studied 46 hypertensive patients with LVH, divided
      into four groups randomly treated with enalapril, hydrochlorothiazide (HCTZ),
      atenolol, or verapamil (SR-V) for 6 months. Office blood pressure and office
      heart rate values were recorded, in basal conditions, after 1 and 6 months of
      treatment, and all patients underwent echocardiography, electrocardiographic
      Holter monitoring, and stress testing. All drugs significantly lowered blood
      pressure, whereas left ventricular mass index was reduced by atenolol, enalapril,
      and SR-V, but not by HCTZ. Treatment induced a significant reduction in the
      number of patients with supraventricular arrhythmias (35 v 15, P < .034, and 28 v
      8, excluding patients treated with HCTZ, P < .008). The number of patients with
      ventricular arrhythmias was also reduced (32 v 16 considering all groups, P <
      .08, and 24 v 9, excluding patients treated with HCTZ, P < .04). The number of
      TEMI during Holter monitoring significantly decreased from 47 to 23 (P = .043) in
      all patients, and from 39 to 14 (P = .013) excluding patients treated with HCTZ.
      In all groups, irrespective of treatment, a reduction of blood pressure, heart
      rate, and systolic blood pressure/heart rate product measured by exercise stress
      test was observed. The present study shows that in hypertensive patients with
      LVH, antihypertensive treatment with atenolol, enalapril and SR-V reduces LVH and
      decreases the prevalence of CA and TEMI. Treatment with HCTZ during the 6-month
      study did not alter LVH and did not appear to reduce CA and TEMI.

PMID- 11465648
TI  - Microalbuminuria as a marker of preclinical diastolic dysfunction in never
      treated essential hypertensives.
AB  - Using 24-h ambulatory blood pressure (BP) monitoring and digitized M-mode
      echocardiography, we evaluated whether microalbuminuria is related to preclinical
      left ventricular (LV) diastolic dysfunction in hypertensive patients. We selected
      87 never-treated hypertensive patients (mean 24-h BP > 140 and/or > 90 mm Hg);
      albuminuria was evaluated as mean value of 24-h urinary albumin excretion (UAE)
      from two 24-h urine collections. Microalbuminuria was found in 28 patients,
      classified as MA+ (UAE 30 to 300 mg/24 h); 59 patients had normal UAE (< 30 mg/24
      h) and were classified as MA-. The MA+ and MA- groups did not differ with regard
      to age, sex, body mass index, or 24-h heart rate, whereas 24-h, daytime, and
      nighttime systolic and diastolic BP were significantly higher in MA+ than in MA-.
      The LV mass index was greater in MA+, as was the prevalence of LV hypertrophy;
      peak shortening rate of LV diameter, index of systolic function, was normal in
      all, but was lower in MA+. Peak lengthening rate of LV diameter and peak thinning
      rate of posterior wall, indices of diastolic function, were lower in MA+ and the
      prevalence of diastolic dysfunction was higher in MA+. UAE was inversely
      correlated with both indices of LV diastolic function, also after correction for
      age, 24-h heart rate, 24-h BP, and LV mass. In conclusion, in never-treated
      hypertensive patients, microalbuminuria is not only associated with greater
      myocardial mass, but is also related with preclinical impairment of LV diastolic
      function. This relation, independent from increased BP or LV mass, strengthens
      the role of microalbuminuria as an early and reliable marker of preclinical
      cardiac involvement.

PMID- 11465649
TI  - Dipping is superior to cusums analysis in assessment of the risk of stroke in a
      case-control study.
AB  - BACKGROUND: Blunted nocturnal decline in blood pressure (BP) is associated with
      increased risk of stroke. Mean day-night BP difference (dipping) and cusums
      derived circadian alteration magnitude (CDCAM) of BP are the common measures of
      diurnal BP variation. Although a significant number of clinical trials have
      demonstrated that dipping is associated with a lower risk of cardiovascular
      events, the clinical value of CDCAM of BP is unknown. We evaluated the
      association between dipping and CDCAM of BP and the risk of stroke. METHODS: We
      analyzed 24-h ambulatory BP recordings of 110 control subjects and 91 stroke
      survivors enrolled in a case-control stroke study. Nondipping was defined as
      nocturnal drop of < 10 mm Hg in systolic BP. The associations between nondipping,
      CDCAM of BP, and risk of stroke were calculated in the same sample. RESULTS:
      There were significantly fewer nondippers in the control group as compared with
      those among the stroke survivors. The odds ratio for stroke of nondippers was
      2.3. By contrast, there was no significant difference in CDCAM of systolic BP
      between the control and stroke survivor groups. This finding could not be
      explained by the presence of reverse dippers in both groups. CONCLUSIONS: In this
      case-control study, classification of subjects into dippers and nondippers was
      found to be more clinically useful than cusums analysis of BP profile. Analysis
      of prospective data is needed to determine the clinical value of the cusums
      analysis of BP profile.

PMID- 11465650
TI  - The effect of sodium supplementation on glucose tolerance and insulin
      concentrations in patients with hypertension and diabetes mellitus.
AB  - Severe short-term sodium restriction or extreme sodium loading may alter glucose
      tolerance and insulin resistance in patients with hypertension, but it is unclear
      whether variations in sodium intake within the clinically observed range affect
      glucose tolerance. To examine this issue, 21 patients with primary hypertension
      with average sodium excretion of 116+/-55 mEq/day were randomized to consecutive
      4-week periods of placebo therapy and sodium chloride supplementation 2 g four
      times a day in a single-blind crossover study design. A 75-g oral glucose
      tolerance test (GTT) with simultaneous insulin levels was performed at the end of
      each intervention period. For the group as a whole, urinary sodium excretion
      increased on sodium chloride to 267+/-118 mEq/day versus control (placebo) phase
      of 135+/-53 mEq/day, P < .001. Total glycemic response in the oral GTT (area
      under the glucose curve) was 8.0% lower during sodium supplementation, P < .001.
      Secondary analysis revealed that the effect of sodium was noteworthy in 1) type 2
      diabetic subjects (n = 8), 2) sodium-sensitive subjects (n = 10), and 3)
      nondiabetic subjects receiving antihypertensive drug treatment (n = 6). The total
      insulinemic response to oral GTT was also lowered by sodium loading among
      diabetic subjects. Thus, an abundant sodium intake may improve glucose tolerance
      and insulin resistance, especially in diabetic, salt-sensitive, and or medicated
      essential hypertensive subjects.

PMID- 11465651
TI  - Valsartan alone or with a diuretic or ACE inhibitor as treatment for African
      American hypertensives: relation to salt intake.
AB  - Previous clinical trials have demonstrated the important influence of ethnicity
      and dietary salt on the antihypertensive efficacy of drugs that block the renin
      angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity
      that have not been widely studied in African American hypertensives, either
      alone, or in combination with other therapies such as diuretics or angiotensin
      converting enzyme inhibitors. We performed a pilot, prospective, open label,
      randomized design clinical trial to evaluate the effects of the angiotensin II
      receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood
      pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq
      Na+/day) for 2 weeks and the same diet supplemented by 100 mEq Na+ for 4 weeks.
      After this evaluation, while continuing the Na+ supplementation, patients were
      randomized to valsartan 320 mg/day (n = 28), or the addition of
      hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the
      valsartan 160 mg/day for an additional 6 weeks. Valsartan (160 mg/day) lowered
      blood pressure significantly in African American patients on both low salt (-6.4/
      4.8 mm Hg: P < .001) and a high salt diet (-4.9/-3.8 mm Hg: P = .01). The high
      salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not
      significant). When comparing the efficacy of the three randomized therapeutic
      regimens while on the Na+ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the
      most effective therapy with an incremental reduction in blood pressure of -10.5/
      6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of
      valsartan to 320 mg incrementally lowered blood pressure by -3.8/-3.3 mm Hg (P =
      not significant). The least effective approach was adding benazepril 20 mg/day to
      valsartan 160 mg/day with no incremental reduction in systolic blood pressure and
      diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant). We
      conclude that in our open label pilot study, the antihypertensive activity of
      valsartan is not significantly attenuated by supplemented salt diet in
      hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be
      the most effective strategy in enhancing the antihypertensive activity of this
      angiotensin II receptor blocker in contrast to either doubling the dose or adding
      an angiotensin converting enzyme inhibitor.

PMID- 11465652
TI  - Outcome survey in unselected hypertensive patients with type 2 diabetes mellitus:
      effects of ACE inhibition.
AB  - Although the benefit of angiotensin converting enzyme (ACE) inhibitors in
      diabetic nephropathy is well documented in double-blind randomized, controlled
      clinical trials, it is uncertain whether the benefit extends to unselected
      patients with diabetes mellitus and arterial hypertension in general practice. In
      2504 unselected patients with type 2 diabetes mellitus (mean age 63+/-10 years)
      blood pressure, cardiovascular, renal, and metabolic parameters were assessed at
      baseline and during a treatment period of 1 year with the ACE inhibitor
      cilazapril by primary care physicians. The average dose of cilazapril was 2.5
      mg/day. Outcome measures were blood pressure, serum creatinine, proteinuria (dip
      stick), HbA1c levels, evaluation of edema, and exertional dyspnea. In the study
      cohort, systolic blood pressure decreased by 24+/-17 mm Hg and diastolic blood
      pressure by 12+/-11 mm Hg. An increase in serum creatinine (> 0.2 mg/dL) occurred
      more frequently in patients with than in those without renal involvement (19% v
      7%; P < .05). Serum creatinine decreased more frequently in patients with renal
      involvement than in those without (26%+/-4% v 12%+/-3.8%; P < .05). Overall renal
      function in patients with diabetic nephropathy (n = 318) improved (2.1+/-1.6
      mg/dL v 1.7+/-1.4 mg/dL; P < .05). The frequency of proteinuria was lower after 1
      year than at baseline (62%+/-9% v 82%+/-8%; P < .05). Metabolic control of
      diabetes mellitus improved in parallel (median HbA1c 8.0% v 7.0%; P < .01).
      Scores for edema formation and exertional dyspnea improved as well (P < .01). In
      this outcome survey of unselected patients with type 2 diabetes mellitus and
      arterial hypertension, the ACE inhibitor cilazapril effectively lowered blood
      pressure, which was associated with an improvement in glucose metabolism, cardiac
      function, and renal function.

PMID- 11465653
TI  - Long-term endothelin receptor blockade improves cardiovascular function in
      diabetes.
AB  - To evaluate the potential contribution of endothelin-1 (ET-1) toward the
      cardiovascular complications of diabetes, the present study examined the effects
      of chronic ET receptor blockade with bosentan on heart function and vascular
      reactivity in streptozotocin (STZ)-induced diabetic rats. Wistar rats were
      divided into four groups: control, control bosentan-treated, diabetic, and
      diabetic bosentan-treated. After chronic bosentan treatment, cardiac function and
      vascular reactivity were assessed. Exvivo working heart function was determined
      in terms of rate of contraction (+dP/dt), rate of relaxation (-dP/dt), and left
      ventricular developed pressure (LVDP). Contractile responses to ET-1 were
      determined in isolated superior mesenteric arteries. In addition, ET-1-like
      immunoreactivity was determined in ventricular and vascular tissues by
      immunohistochemistry. Cardiac function was depressed in the untreated-diabetic
      group. Bosentan treatment improved working heart function; hearts from the
      diabetic bosentan-treated group exhibited improved LVDP and -dP/dt. The
      contractile responses of mesenteric arteries to ET-1 were exaggerated in the
      untreated-diabetic group. Long-term bosentan treatment normalized these
      responses. Immunohistochemical analyses revealed increased ET-1-like
      immunoreactivity in ventricular and vascular tissues from untreated diabetic
      rats. These data show the beneficial effects of ET(A/B) receptor blockade on
      cardiovascular function in STZ-diabetic rats. An altered ET-1 system may
      contribute toward the pathogenesis of cardiovascular dysfunction in diabetes.

PMID- 11465654
TI  - Does the antihypertensive response to angiotensin converting enzyme inhibition
      predict the antihypertensive response to angiotensin receptor antagonism?
AB  - To test the hypothesis that the antihypertensive response to angiotensin
      converting enzyme (ACE) inhibition can predict the response to angiotensin II
      type I receptor (AT1R) antagonism, 33 hypertensive patients were randomized to
      receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks. Patients were then
      crossed-over to the alternative treatment for a second 5-week period. Twenty-four
      hour ambulatory BP (ABP) was measured before randomization and on the final day
      of each period. The agreement in ABP response between the two drugs was assessed
      using the following approaches: Subjects were classified as responders and
      nonresponders using as a threshold an arbitrary level of response (ABP fall > or
      = 10 mm Hg systolic or > or = 5 mm Hg diastolic) or the median ABP response
      achieved by each of the drugs. Disagreement between the two drugs in the
      responders-nonresponders classification was expressed as the proportion of
      subjects whose ABP responded to one of the drugs only. Lisinopril was more
      effective than losartan in reducing ABP (mean difference 4.7+/-8.1/3.3+/-5.7 mm
      Hg, systolic/diastolic, P < .05). Disagreement in the antihypertensive response
      between the two drugs was found in 39%/33% of subjects for systolic/diastolic ABP
      using the arbitrary response criterion (33%/39% using the median response
      criterion). Significant correlations were found between the responses to
      lisinopril and losartan (r = 0.47/0.59, systolic/diastolic, P < .01). We conclude
      that in more than one third of hypertensive subjects, the BP response to ACE
      inhibition fails to predict the response to AT1R antagonism and vice versa. These
      data suggest that there are differences between these two drug classes that are
      not only of theoretical but also of practical significance.

PMID- 11465655
TI  - Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean
      hypertensive subjects.
AB  - The purpose of this study was to determine the contribution of the adrenergic
      system in mediating hypertension in obese and lean patients. Thirteen obese,
      hypertensive patients with a body mass index (BMI) > or =28 kg/m2 (obese) and
      nine lean patients with a BMI < or =25 kg/m2 (lean) were recruited. After a 1
      week washout period, participants underwent daytime ambulatory blood pressure
      monitoring (ABPM). Participants were then treated with the alpha-adrenergic
      antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the beta
      adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and
      titrated to 50 mg/day within 1 week. One month after the addition of atenolol,
      all patients underwent a second ABPM session. There were no differences between
      the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean
      arterial pressures (MAP) measured by office recording or ABPM. However, obese
      subjects had higher heart rates than lean subjects (87.5+/-2.4 v 76.8+/-4.9
      beats/min). After 1 month of treatment with the adrenergic blockers, obese
      patients had a significantly lower SBP (130.0+/-2.5 v 138.9+/-2.1 mm Hg, P = .02)
      and MAP (99.6+/-2.3 v 107.0+/-1.5 mm Hg, P = .02) than lean patients. Obese
      patients also tended to have a lower DBP than lean patients (84.3+/-2.5 v 90.9+/
      1.6 mm Hg, P = .057), but there was no significant difference in heart rate after
      1 month of adrenergic blockade. These results indicate that blood pressure is
      more sensitive to adrenergic blockade in obese than in lean hypertensive patients
      and suggest that increased sympathetic activity may be an important factor in the
      maintenance of hypertension in obesity.

PMID- 11465656
TI  - Effect of combination hormone replacement therapy on ambulatory blood pressure
      and arterial stiffness in diabetic postmenopausal women.
AB  - BACKGROUND: Diabetes mellitus negates the premenopausal gender benefit with
      respect to coronary artery disease. Whether hormone replacement therapy (HRT)
      offers any cardiovascular advantage to diabetic postmenopausal women is not
      known. Diabetic subjects have increased vascular load and abnormal 24-h blood
      pressure (BP) profiles. Hormone replacement therapy has been shown to improve
      indexes of arterial load in nondiabetic postmenopausal women as well as to
      restore circadian variation in BP. This aim of this study, therefore, was to
      determine prospectively whether HRT improved arterial stiffness and 24-h
      ambulatory BP profile in diabetic postmenopausal women. METHODS: Twelve diabetic
      postmenopausal women were studied. Six subjects were also hypertensive. Vascular
      load was characterized by carotid arterial pulse waveform analysis to calculate
      central augmentation index. All subjects also underwent 24-h BP monitoring.
      Subjects were studied before commencement of HRT and were then randomized to two
      groups. The first group was observed for 6 months and then given 2 months of
      estrogen alone, followed by 4 months of combination estrogen with progestin. The
      second group received the HRT regimen first, then were restudied after 6 months
      off HRT. RESULTS: The HRT did not affect either clinic or ambulatory BP. There
      were no changes in indexes of vascular load or pulse pressure, an indirect
      measure of arterial stiffness. There was a low rate of circadian variation in 24
      h BP at baseline (55%), which was unaltered by HRT. CONCLUSIONS: The HRT was well
      tolerated. Despite evidence for a beneficial effect of HRT on indexes of arterial
      load and ambulatory BP previously reported in normal subjects, we found no change
      in this cohort of diabetic postmenopausal women.

PMID- 11465657
TI  - Bone mineral density in women with essential hypertension.
AB  - Recent studies have reported the abnormalities in calcium metabolism at the
      systemic level in human hypertension as well as in experimental hypertension.
      Because bone is the largest store of calcium in the body, the bone calcium
      content and mineralization may represent the entire calcium balance. The present
      study was undertaken to investigate the bone mineral density (BMD) in women with
      essential hypertension by means of the dual-energy X-ray absorptiometric (DXA)
      method. The DXA analysis showed a significant decrease in BMD in female
      hypertensive subjects compared with normotensive subjects. In addition, the BMD
      was inversely correlated with systolic blood pressure in women. The 24-h urinary
      calcium excretion was significantly greater in female hypertensive subjects than
      in female normotensive subjects. Furthermore, the greater the urinary calcium
      excretion, the lower the BMD in women. The values of serum total calcium, total
      magnesium, ionized calcium, and 1, 25(OH)2 vitamin D were not different between
      hypertensive and normotensive subjects. The results of the present study
      demonstrated that DXA provided an index of whole calcium balance, and suggest
      that high blood pressure might be associated with reduced BMD in female
      hypertension.

PMID- 11465658
TI  - Voluntary running improves glucose tolerance and insulin resistance in female
      spontaneously hypertensive rats.
AB  - We evaluated the effects of voluntary exercise training on glucose metabolism and
      measures of insulin sensitivity in female spontaneously hypertensive rats (SHR).
      Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls.
      Exercising SHR were housed in running wheels for 8 weeks (SHRx8) or 16 weeks
      (SHRx16). At 22 weeks of age, we measured systolic blood pressure, performed oral
      glucose tolerance tests, and determined hexokinase activity and glucose
      transporter (GLUT) 4 content in skeletal muscle to assess intracellular glucose
      metabolism. Blood pressure was lower in WKY (139+/-12 mm Hg) than untrained SHR
      (216+/-13 mm Hg). Exercise training caused a reduction in blood pressure (-18 mm
      Hg) for SHRx8. After a brief (5-h) fast, serum glucose was lower in SHR that
      exercised compared with sedentary SHR, whereas insulin concentrations were
      identical between all SHR and WKY. Corresponding free fatty acids (FFA) were
      twofold higher in SHR than in WKY. In response to glucose, SHR demonstrated
      higher glucose and FFA responses, with exercise decreasing the glucose values in
      a dose-dependent manner. Although the insulin response was comparable in all
      groups, the glucose-to-insulin ratio was higher in SHR, indicating a relative
      insulin resistance for both glucose disposal and suppression of free fatty acids.
      Hexokinase activity and GLUT4 content were elevated 1.4- and 2.8-fold,
      respectively, in plantaris muscle of SHRx16, suggesting an improvement in the
      capacity for glucose transport and phosphorylation with exercise. These results
      provide evidence that voluntary running in female SHR lowers blood pressure and
      selectively increases glucose uptake and insulin action, but not suppression of
      FFA.

PMID- 11465659
TI  - Regulation of pressure-activated channel in intact vascular endothelium of stroke
      prone spontaneously hypertensive rats.
AB  - The pressure-activated cation channel (PAC), a novel type of mechanosensitive
      channel, has been suggested to act as a mechanosensor in aortic endothelium. In
      experimental hypertension, PAC function was up-regulated in the established phase
      of high blood pressure. This association of altered PAC function and elevated
      arterial pressure suggests that PAC function is regulated by alterations in blood
      pressure. In the present study, we electrophysiologically investigated PAC
      function in intact endothelium of aorta (EA) and mesenteric artery (EMA) from
      stroke-prone spontaneously hypertensive rats (SHRSP), SHRSP after 4 weeks of
      treatment with quinaprilat (10 mg/kg/day), and normotensive Wistar-Kyoto (WKY)
      rats. In untreated SHRSP and WKY rats, systolic blood pressure (SBP) was 201+/-3
      mm Hg and 142+/-3 mm Hg, respectively. In quinaprilat-treated SHRSP, SBP was
      lowered to 135+/-5 mm Hg. Apparent PAC density (percentage of patches with PAC
      activity) in EA of untreated SHRSP (63.7%+/-7.3%) was 2.4-fold higher than in WKY
      rats (26.0%+/-5.0%). In contrast, no significant PAC up-regulation was detected
      in EMA of SHRSP (15.7%+/-4.2%) compared with WKY rats (12.0%+/-3.9%). In EA of
      quinaprilat-treated normotensive SHRSP, PAC density (27.1%+/-5.2%) was lowered to
      levels found in normotensive WKY rats. Unitary conductance and pressure
      sensitivity of PAC were not altered in either hypertensive or normotensive rats.
      Taken together, hypertension-induced increases of endothelial PAC density can be
      completely reversed by antihypertensive therapy. The PAC up-regulation in EA was
      interpreted as a compensatory mechanism to enhance Ca2+-influx and subsequently
      the synthesis of vasodilatory factors. This mechanism is missing in EMA of SHRSP,
      which might contribute to high blood pressure in this rat model of severe genetic
      hypertension.

PMID- 11465660
TI  - Enhanced neutrophil superoxide anion production and its modification by beraprost
      sodium in spontaneously hypertensive rats.
AB  - To clarify the function of polymorphonuclear leukocytes (PMN) in spontaneously
      hypertensive rats (SHR) and the effect of beraprost sodium (BS) on these
      functions, we examined superoxide anion (O2-) production and adherent activity by
      PMN, as well as modification of these functions by BS ex vivo and in vitro. In
      study 1, we measured PMN functions in 4-week-old SHR and Wistar-Kyoto (WKY) rats.
      In study 2 (ex vivo), 14-week-old SHR received vehicle (n = 6) and BS (30
      microg/kg/day [n = 6] and 100 microg/kg/day [n = 7]) once daily for 4 weeks. In
      study 3 (in vitro), PMN from 18-week-old SHR were incubated with BS (0.1 and 1
      micromol/L) and theophylline (200 micromol/L), which is reported to inhibit the
      PMN O2- production. Systolic blood pressure, platelet counts, and PMN O2-
      production stimulated by phorbol ester myristate acetate were significantly
      elevated in 4-week-old SHR compared with WKY (P < .05). Beraprost sodium
      decreased the ex vivo PMN O2- production, serum superoxide dismutase activity,
      and platelet counts (P < .05); however, BS did not reduce the in vitro PMN O2-
      production. These data support our hypothesis that the enhanced PMN function
      contributes to the cardiovascular damages during the early phase of SHR, and that
      BS has merit for preventing the O2- related organ damages in this model.

PMID- 11465661
TI  - Pheochromocytoma in a symptomatic patient with severe hypertension upon
      anesthesia induction.

PMID- 11465662
TI  - Safety of nicotine in smokers with hypertension.

PMID- 11465663
TI  - Uncertainty management in integrated assessment modeling: towards a pluralistic
      approach.
AB  - Integrated Assessment (IA) is an evolving research community that aims to address
      complex societal issues through an interdisciplinary process. The most-widely
      used method in Integrated Assessment is modeling. The state of the art in
      Integrated Assessment modeling is described in this paper in terms of history,
      general features, classes of models, and in terms of the strengths and
      weaknesses, and the dilemmas and challenges modelers face. One of the key
      challenges is the issue of uncertainty management. The paper outlines the sources
      and types of uncertainty modelers are confronted with. It then discusses how
      uncertainties are currently managed in Integrated Assessment modeling, on which
      evaluation it is argued that complementary methods are needed that allow for
      pluralistic uncertainty management. The paper finalises with discussing
      pluralistic concepts and approaches that are currently explored in the IA
      community and that seem promising in view of the challenge to incorporate
      explicitly more than one hidden perspective in models.

PMID- 11465664
TI  - Strategies used to guide the design and implementation of a national river
      monitoring programme in South Africa.
AB  - This article explores the strategies that were, and are being, used to facilitate
      the transition from scientific development to operational application of the
      South African River Health Programme (RHP). Theoretical models from the field of
      the management of technology are used to provide insight into the dynamics that
      influence the relationship between the creation and application of environmental
      programmes, and the RHP in particular. Four key components of the RHP design are
      analysed, namely the (a) guiding team, (b) concepts, tools and methods, (c) infra
      structural innovations and (d) communication. These key components evolved over
      three broad life stages of the programme, which are called the design, growth and
      anchoring stages.

PMID- 11465665
TI  - Monitoring and biomonitoring of surface ozone in Florence, Italy.
AB  - An ambient air study was conducted in the city of Florence, Italy, in the summer
      1996. Tropospheric ozone was continuously monitored with automatic analyzers in
      three stations, two located in the urban area and one in the hilly surroundings
      (Settignano). A biomonitoring campaign based on the tobacco cv. Bel-W3 plants was
      performed in the same area. The highest values were constantly recorded in the
      Settignano station. The highest 1-hour mean recorded was 197 nl/l; the
      accumulated exposure over a threshold of 40 nl/l (AOT40) was well above the
      critical levels standards for protection of the vegetation. A consistent temporal
      variation was observed and July proved to be the month with the highest ozone
      levels. Cumulative frequency distribution of ozone maximum daily concentrations
      exhibited a good fitting to log-normality. No 'week-end' effect was observed.
      Biomonitoring data were in good agreement with chemico-physical ones.

PMID- 11465666
TI  - Temporal variation of PCDD/PCDF levels in environmental samples collected near an
      old municipal waste incinerator.
AB  - In 1996 and 1997, the levels of polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs) were determined in soil and herbage samples taken from 24
      sites in the vicinity of an old municipal solid waste incinerator (Montcada,
      Barcelona, Spain). To determine the temporal variation in the concentrations of
      PCDD/Fs, recently 24 soil and 24 herbage samples were again collected at the same
      sampling points and analyzed for PCDD/F levels. In the current survey, PCDD/F
      concentrations in soils ranged between 0.06 and 127 ng I-TEQ kg(-1) (dry matter),
      with median and mean values of 4.80 and 9.95 ng I-TEQ kg(-1) (dry matter),
      respectively. In turn, the levels of PCDD/Fs in herbage samples ranged from 0.40
      to 1.94 ng I-TEQ kg(-1) (dry matter), with median and mean values of 0.86 and
      0.95 ng I-TEQ kg(-1) (dry matter), respectively. The comparison with the data
      obtained in 1996 and 1997 show that while PCDD/F concentrations in herbage
      samples decreased substantially during the last two years, no significant
      differences in the levels of PCDD/Fs in soils were noted. On the other hand, the
      potential intake of polluted soils from the vicinity of the plant would not imply
      any significant health risk for the general population living in the area under
      influence of the facility.

PMID- 11465667
TI  - Metal levels in feathers of cormorants, flamingos and gulls from the coast of
      Namibia in southern Africa.
AB  - Arsenic, cadmium, chromium, lead, manganese, mercury, selemium, and tin
      concentrations were measured in the feathers of Cape cormorant (Phalacrocorax
      capensis), Hartlaub's gull (Larus hartlaubii), kelp gull (Larus dominicanus), and
      lesser flamingo (Phoeniconaias minor) from the coast of Namibia in southern
      Africa. Metal concentrations in feathers represent the concentrations in the
      blood supply at the time of feather formation. Cape Cormorants are piscivores;
      kelp gulls are primarily piscivores; Hartlaub's gull is an omnivore; and lesser
      flamingos eat primarily blue-green algae and invertebrates filtered from the
      water and sediment of hypersaline lagoons. We predicted that metal concentrations
      would reflect these trophic level differences. There were significant species
      differences in the concentrations of all metals, with flamingos having the lowest
      levels, and cormorants having the highest levels of 4 metals but not mercury. The
      gulls had the highest levels of mercury, perhaps reflecting their more scavenging
      behavior.

PMID- 11465668
TI  - Effectiveness of an influenza vaccine used in Poland in the 1998-1999 influenza
      season.
AB  - The aim of this study was to evaluate the effectiveness of the influenza vaccine
      used at the Proelmed Medical Center, Poland during the influenza season 1998
      1999. The study randomised patients attending the Proelmed Medical Center, Poland
      to receive influenza vaccination or not. Volunteers were monitored for the
      following 6 months by interviews at which systemic and local symptoms were
      recorded. 193 volunteers were randomised to receive influenza vaccine and 206 to
      the control group. In the vaccinated group, 7 cases (3.7%) of influenza were
      recorded, compared to 59 cases (28.6%) in the unvaccinated group. Respiratory
      disease other than influenza occurred in 29.5% of the vaccinated group and 34.5%
      of the unvaccinated group. Vaccinated patients had a total of 62 days off sick
      due to influenza, compared to 467 days for the unvaccinated patients. No
      unexpected adverse events were reported. The influenza vaccine used is highly
      efficacious in protecting against influenza infection leading to absenteeism from
      work, and has a good safety profile.

PMID- 11465669
TI  - Human heterophile antibodies recognizing distinct carbohydrate epitopes on
      basidiolipids from different mushrooms.
AB  - Investigating the immune properties of basidiolipids, i.e.,
      glycoinositolphosphoceramides (GIPC) of basidiomytes, higher mushrooms, it was
      detected that sera of normal adult human subjects contained IgG2 and IgM
      heterophile antibodies (hetAbs) that immunoreacted with these lipids. However,
      this immune recognition was not shared by the glycolipids of all mushroom
      species. The basidiolipids of Amanita virosa (eng., death cup) and Cantharellus
      cibarius (engl., chantarelle), of all mushroom species studied, did not bind
      antibodies of normal human sera. In addition, only certain basidiolipids of the
      other mushroom species that have been investigated, i.e., Agaricus bisporus
      (engl., field mushroom), Calvatia exipuliformis engl., puffball), Lentinus edodes
      (jap., Shiitake), Leccinum scabrum (engl., red birch boletus), and Pleurotus
      ostreatus (engl., oyster mushroom), immunoreacted with the human hetAbs. The
      basidiolipids that were recognized by the human hetAbs had either terminal
      Galalpha1-6Gal < or Galbeta1-6Man< epitopes. Enzymatic destruction of the
      respective carbohydrate epitopes abolished the previous immune reactivity. It is
      assumed that contact with non human antigens causes generation of the anti
      basidiolipid antibodies.

PMID- 11465670
TI  - The application of Artocarpus integer seed lectin-M in the detection and
      isolation of selective human serum acute-phase proteins and immunoglobulins.
AB  - Champedak (Artocarpus integer) lectin-M is a lectin with high specificity and
      affinity for the core-mannosyl residues of the N-linked oligosaccharides of
      glycoproteins. We have studied the interaction of the champedak seed lectin with
      human serum glycoproteins that were resolved by 2-dimensional (2-D) gel
      electrophoresis. The lectin demonstrated strong interaction with haptoglobin beta
      chain, orosomucoid, alpha1-antitrypsin, alpha2-HS glycoprotein, transferrin,
      hemopexin, alpha1B-glycoprotein, and the heavy chains of IgA, IgM and IgG of the
      human serum. With exceptions of the heavy chains of the immunoglobulins and
      alpha1B-glycoprotein, all the other lectin-M-probed glycopeptides are acute-phase
      proteins. The use of champedak lectin-M to probe for serum glycoproteins that
      were separated in a 2-D gel electrophoresis and Western blotting technique may be
      conveniently applied to analyse the acute-phase and humoral immune responses
      simultaneously. Subjecting human serum to immobilised-lectin-M affinity
      chromatography was able to isolate intact haptoglobin, alpha1-antitrypsin,
      alpha1B-glycoprotein, hemopexin and IgA.

PMID- 11465671
TI  - Soluble thrombospondin-1 suppresses T cell proliferation and enhances IL-10
      secretion by antigen presenting cells stimulated with phytohemagglutinin.
AB  - Thrombospondin-1 (TSP-1) is different from other components of the extracellular
      matrix (ECM) regarding its production and distribution. TSP-1 is considered to be
      released in large quantity in inflammatory sites and exogenously added TSP-1 does
      not bind to preformed ECM but instead binds to cells. To define the physiological
      role of TSP-1 in the immune system, we studied the influence of TSP-1 on the in
      vitro culture of T cells and antigen-presenting cells (APCs) in the presence of
      phytohemagglutinin. By adding soluble TSP-1 to the culture, T cell proliferation
      was suppressed and anti-inflammatory cytokine IL-10 secretion by APCs was
      enhanced. The enhanced expression of IL-10 was also demonstrated at the mRNA
      level by RT-PCR using multiprimer kit for cytokines. The suppression of T cell
      proliferation and the enhancement of IL-10 secretion with soluble TSP-1 was
      inhibited byadding RGDS peptide or heparin. This result indicates that the effect
      of soluble TSP-1 may be caused by binding to its ligand(s) on T cells and/or
      APCs, resulting in transducing regulatory signals to the cells or disturbing
      appropriate interaction between T cells and APCs. We therefore propose that TSP-1
      is an immunosuppressive modulator which may play a role in inflammatory sites.

PMID- 11465672
TI  - Telomere-independent reduction of human B lymphocyte: proliferation during long
      term culture.
AB  - Telomeres and telomerase, the telomere lengthening enzyme, have been shown to
      play a central role in the long-term ability of cells to proliferate and maintain
      viability. In opposition to transformed cells, normal somatic cells express a low
      level of telomerase, which results in the gradual shortening of their telomeres
      after each division and in cell senescence once a critical telomere length is
      reached. We have tested the hypothesis that shortening of telomeres could limit
      the expansion of normal human B lymphocytes maintained in long-term culture using
      a CD40/CD154 system. Measurement of temolerase activity in cell lysates showed a
      rapid up-regulation of telomerase following the initiation of the culture that
      was dependent on the CD40 signaling. The high level of telomerase activity and
      the corresponding long telomere structures remained constant for the 35 day
      culture period in which a gradual reduction of the cell expansion rate is
      observed. We conclude that the gradual in vitro senescence of cultured B cells
      does not correlate with a corresponding loss of telomerase activity and of
      telomere length. Rather the phenomenon may be related to an intrinsic property of
      the proliferating B cells to differentiate into Ig-secreting cells.

PMID- 11465673
TI  - The T lymphocyte structure CD60 contains a sialylated carbohydrate epitope that
      is expressed on both gangliosides and glycoproteins.
AB  - The CD60 antigen is expressed on a majority of T cells in autoimmune lesions, and
      anti-CD60 can activate T lymphocytes. CD60 has been defined as the GD3
      ganglioside, and subsequently as the 9-O-acetylated form of GD3. However, other
      evidence suggests that anti-CD60 recognizes a glycoprotein or family of
      glycoproteins expressed by T lymphocytes. The current studies were undertaken to
      better define the identity of the CD60 antigen on both T cells and non-T cells.
      Treatment of intact cells with neuraminidases of various specificities confirmed
      that detection of the CD60 epitope depends on expression of an alpha2, 8-disialic
      acid carbohydrate linkage, as is found in GD3 and related gangliosides. However,
      the sialicacid polymer colominic acid inhibited anti-GD2 and anti-GD3, but not
      anti-CD60 from binding to cell surfaces. Expression of CD60 did not correlate
      with expression of GD3 on a variety of cell lines and T cell populations.
      Expression of CD60 and 9-O-acetyl-GD3 was roughly parallel on some non-T cell
      lines such as melanoma cells, but on T cells expression of CD60 was consistently
      greater. Antibodies to GD2, GD3 and 9-O-acetyl-GD3 were ineffective at inhibiting
      binding of anti-CD60 to CD60+ cells. Activation responses of T cells to anti-CD60
      were inducible in either the presence or absence of a response to anti-GD3. A
      novel inhibitor of glucosyl ceramide synthesis, D-threo-1-phenyl-2-palmitoylamino
      3-pyrrolidino-1-propanol (D-t-P4) reduced expression of GD3 much more than CD60
      on activated T lymphocytes. Following biotinylation of HUT78 T cells, anti-CD60
      immunoprecipitated a 70 kDa antigen. Taken together, the present data and
      previous findings suggest that anti-CD60 can recognize both a modified form of
      the GD3 ganglioside and a carbohydrate-dependent complex epitope present on one
      or more glycoproteins. This glycoprotein epitope may be the more abundant and
      functionally significant CD60 antigen on T lymphocytes, while 9-O-acetyl-GD3 is
      likely to be the principal structure recognized by anti-CD60 on melanoma cells.
      These findings emphasize the complexity of understanding the functional roles of
      carbohydrate epitopes in cell activation.

PMID- 11465674
TI  - Identification of differentially expressed genes in human memory (CD45RO+) CD4+ T
      lymphocytes.
AB  - The precise nature and development of the memory (CD45RO+) CD4+ T lymphocytes
      remain unknown. In this study, we analyzed differential gene expression of human
      memory CD4+ T lymphocytes in relation to their naive counterparts. A suppression
      subtractive hybridization technique was used to isolate and clone differentially
      expressed genes in the memory subset with respect to the naive subset. We
      screened approximately 300 clones by dot blot analysis and sequenced 23
      differentially expressed clones. GenBank sequence homology search showed that
      these clones included genes for transcription factors, enzymes and
      immunomodulatory molecules. Differential expression of a subset of these genes
      was further confirmed by RT-PCR and densitometric analysis revealed that they
      were expressed five to eightfold more in memory than naive CD4+ T lymphocytes.
      Collectively, these results suggest that multiple genes with different functions
      contribute to the development of immunological memory in human T lymphocytes.

PMID- 11465675
TI  - The neuropsychology and neuroanatomy of bipolar affective disorder: a critical
      review.
AB  - Bearden CE, Hoffman KM, Cannon TD. The neuropsychology and neuroanatomy of
      bipolar affective disorder: a critical review. Bipolar Disord 2001: 3: 106 150. C
      Munksgaard, 2001 OBJECTIVES: To present a comprehensive review of the existing
      neuropsychological and neuroimaging literature on bipolar affective disorder.
      This review critically evaluates two common conceptions regarding the
      neuropsychology of bipolar disorder: 1) that, in contrast to schizophrenia,
      bipolar affective disorder is not associated with general cognitive impairment
      independent of illness episodes, and 2) relative right hemisphere (RH)
      dysfunction is implicated in bipolar illness patients, supported by reports of
      relatively greater impairment in visuospatial functioning, lateralization
      abnormalities, and mania secondary to RH lesions. METHODS: The major computerized
      databases (Medline and PSYCInfo) were consulted in order to conduct a
      comprehensive, integrated review of the literature on the neuropsychology and
      neuroanatomy of bipolar disorder. Articles meeting specified criteria were
      included in this review. RESULTS: In a critical evaluation of the above notions,
      this paper determines that: 1) while there is little evidence for selective RH
      dysfunction, significant cognitive impairment may be present in bipolar illness,
      particularly in a subgroup of chronic, elderly or multiple-episode patients,
      suggesting a possible toxic disease process, and 2) the underlying functional
      correlate of these cognitive deficits may be white matter lesions ('signal
      hyperintensities') in the frontal lobes and basal ganglia, regions critical for
      executive function, attention, speeded information processing, learning and
      memory, and affect regulation. While this hypothesized neural correlate of
      cognitive impairment in bipolar disorder is speculative, preliminary functional
      neuroimaging evidence supports the notion of frontal and subcortical
      hypometabolism in bipolar illness. CONCLUSIONS: The etiology of the structural
      brain abnormalities commonly seen in bipolar illness, and their corresponding
      functional deficits, remains unknown. It is possible that neurodevelopmental
      anomalies may play a role, and it remains to be determined whether there is also
      some pathophysiological progression that occurs with repeated illness episodes.
      More research is needed on first-episode patients, relatives of bipolar probands,
      and within prospective longitudinal paradigms in order to isolate disease
      specific impairments and genetic markers of neurocognitive function in bipolar
      disorder.

PMID- 11465676
TI  - On defining 'mood stabilizer'.

PMID- 11465677
TI  - Bupropion manic induction during euthymia, but not during depression.

PMID- 11465678
TI  - Topiramate for self-mutilation in a patient with borderline personality disorder.

PMID- 11465679
TI  - The last straw--suicide: prevention, policy, and prevalence.

PMID- 11465680
TI  - Bioethics, assisted suicide, and the "right to die".
AB  - Physician-assisted suicide is much talked about. But confusion remains as to what
      precisely it is, and debate continues about its ethical implications. Is
      physician-assisted suicide distinguishable from refusal of treatment? Is there a
      "right to die?" Does assisted suicide necessarily have to mean physician-assisted
      suicide? What is the relationship of physician-assisted suicide to end-of-life
      care? How should physicians deal with a request for assisted suicide? These
      issues are explored in this paper, along with a review of the ethical arguments
      for and against physician-assisted suicide. The paper concludes that society
      should encourage individuals not to see assisted suicide as their best option. A
      better policy than widespread legalization of physician-assisted suicide is to
      provide the necessary social support, health care including mental health care,
      hospice care, and compassion to those who feel they face an undignified life, or
      an undignified painful death. This paper is based on a presentation made at the
      AACP 2000 Annual Meeting, October 14, 2000.

PMID- 11465681
TI  - Traumatic grief in a convenience sample of victims seeking support services after
      a terrorist incident.
AB  - This report describes traumatic grief in 40 individuals who suffered losses in
      the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City. We
      administered a self-report instrument 6 months after the bombing to assess
      demographics; exposure; injury; retrospective report of initial emotional and
      physiological reaction; and current posttraumatic stress symptoms, grief, safety
      concerns, and functioning. A strong association was found between posttraumatic
      stress symptoms and grief. The relationship between grief and difficulty
      functioning was stronger at higher levels of posttraumatic stress than at lower
      levels. The results support the construct of traumatic grief and have important
      implications for the treatment of people exposed to large-scale traumatic events
      and for the training of mental health professionals.

PMID- 11465682
TI  - The association of irritable bowel syndrome and somatization disorder.
AB  - BACKGROUND AND OBJECTIVE: Irritable bowel syndrome (IBS) and somatization
      disorder (SD) are defined by nonobjective symptoms that overlap considerably.
      Psychiatric symptoms associated with IBS may originate from SD in IBS patients.
      Previous studies of IBS have not considered SD separately from IBS. METHODS: This
      study explored psychiatric symptoms and illness behavior in IBS in relation to
      SD. A total of 50 outpatients with IBS or ulcerative colitis (UC) were evaluated
      with the Diagnostic Interview Schedule and Illness Behavior Questionnaire.
      RESULTS: Definite or probable SD was diagnosed in no UC patients and in 42% of
      IBS patients (confirmed in 25% and lacking one symptom in another 17%). IBS
      patients with probable or definite SD, but not those without SD, reported more
      psychiatric symptoms and abnormal illness behaviors than did UC patients. SD
      accounted for the association of psychiatric symptoms with IBS. CONCLUSIONS: In
      this university-based office setting, the association of psychiatric features
      with IBS appears heterogeneous predicated on whether SD is present. Future
      studies of functional bowel diseases should distinguish between patients with and
      without SD to clarify its relationship to these disorders. Clinicians should
      consider whether patients with functional disorders have SD, a diagnosis that
      indicates specific clinical management strategies.

PMID- 11465683
TI  - Use of antidepressants in treatment of comorbid diabetes mellitus and depression
      as well as in diabetic neuropathy.
AB  - After a brief review of epidemiology, the focus is on biochemistry of diabetes.
      Animal and human studies are reviewed in terms of the impact of alterations in
      catecholamines and serotonin (5-hydroxytryptamine, 5HT) on glucose utilization.
      Then, the implications of these experimental results for the choice of
      antidepressant in comorbid diabetes mellitus and depression as well as in
      diabetic neuropathy are discussed. Results of clinical investigations are then
      reviewed in terms of the above hypotheses. An Index Medicus Search for the past
      10 years was supplemented by references from previous related reviews of the
      topic as well as by pending results, where available, not previously published.
      The range of prevalence of depression in diabetic patients has been 8-27%,
      depending on study criteria and procedures. An increase of catecholamines appears
      to increase glucose while both reducing insulin release and reducing sensitivity
      to insulin that is available. In contrast, increases in serotonergic function by
      increased precursor, increased release, or blocked metabolism and blocked
      reuptake in contrast seem to increase sensitivity to insulin and reduce plasma
      glucose. There have been six studies of fluoxetine, a selective serotonin
      reuptake inhibitor (SSRI), at a dose of 60 mg/day pursued up to 12 months that
      have demonstrated that medication's usefulness in diabetic patients, with
      reductions in weight (to 9.3 kg), in FPG (to 45 mg%), and in HbA1c (to 2.5%). In
      studies in comorbid diabetes mellitus and depression, nortriptyline, a
      norepinephrine reuptake inhibitor that produces increased synaptic catechols, has
      led to worsening of indices of glucose control. However, fluoxetine and
      sertraline, both selective serotonin reuptake inhibitors, in the same patient
      group, have produced results consistent with reductions in glucose levels. In
      diabetic neuropathy, perhaps due to the fact that catecholamines and serotonin
      may both be implicated in pain pathways, dual-action antidepressants appear more
      effective at lower doses than do specific serotonergic agents. The tricyclic
      antidepressants (TCA) (66.7%) have had success in double-blind studies,
      particularly imipramine, with a 81% response rate. Yet, there are positive
      reports concerning the SSRIs (paroxetine, citalopram, sertraline), as well as
      nefazodone, that focus on serotonin selectivity. CONCLUSIONS: In comorbid
      diabetes mellitus and depression, most evidence supports the use of fluoxetine in
      control of glucose handling. Other characteristics in terms dosing, drug
      interactions, cognition, and sleep make sertraline an attractive alternative
      agent. In diabetic neuropathy without depression, the best choices among non-TCAs
      may include sertraline, citalopram, and perhaps, venlafaxine, since the TCAs
      appear to increase cravings and increase FBG levels.

PMID- 11465684
TI  - Study to assess the compensation and skills of medical library professionals
      relative to information technology professionals.
AB  - PURPOSE: The study seeks to determine how medical library professionals
      performing information-technology (IT) roles are compensated and how their
      positions are designed compared to information technology staff in their
      institutions. METHODS: 550 medical library directors in hospital and academic
      medical libraries were surveyed. The data was then compared to survey data from
      other compensation studies of the IT industry. RESULTS: There is a gap in
      compensation between medical library professionals and IT professionals
      performing similar functions using information technology. Technology-intense
      library jobs are compensated at higher levels than more traditional jobs.
      CONCLUSIONS: To compete with IT salaries, managers of medical library
      professionals will need to be ever more cognizant of the employment practices of
      IT professionals in nonmedical library disciplines. It is typically in the
      medical library's best interest to ensure that IT-related jobs, accountabilities,
      and capabilities of the medical library are known and understood by others,
      especially in the human resources and information technology staff departments.

PMID- 11465685
TI  - Web-based Loansome Doc, librarians, and end users: results from a survey of the
      Southeast Region.
AB  - OBJECTIVES: The study examines how Loansome Doc services are implemented and used
      by libraries in the Southeast Region and describe end users' experiences with and
      attitudes toward Loansome Doc. METHODS: 251 active DOCLINE libraries and 867
      Loansome Doc users were surveyed. RESULTS: Roughly one half of the libraries
      offered Loansome Doc services. Of those that did not, most indicated no plans to
      offer it in the future. The majority had a small number of end users and
      experienced minimal increases in interlibrary loan activity. Problems were
      relatively rare. Satisfaction with Loansome Doc was high among all types of
      libraries. End users were usually physicians or other health care professionals
      who requested articles for research and patient care. Most learned about Loansome
      Doc through PubMed or Internet Grateful Med. End users appeared to be largely
      self-taught or received informal instruction in Loansome Doc. Loansome Doc filled
      document requests in a timely manner, and end users reported being satisfied with
      the service. CONCLUSIONS: Greater promotion of what Loansome Doc is and how it
      can benefit libraries can increase the number of participating libraries. While
      satisfaction of Loansome Doc end users is high, satisfaction could be increased
      with more help on the PubMed screen, more library training, and faster delivery
      methods.

PMID- 11465686
TI  - Raising the bar: the importance of hospital library standards in the continuing
      medical education accreditation process.
AB  - The Connecticut State Medical Society (CSMS) reviews and accredits the continuing
      medical education (CME) programs offered by Connecticut's hospitals. As part of
      the survey process, the CSMS assesses the quality of the hospitals' libraries. In
      1987, the CSMS adopted the Medical Library Association's (MLA's) "Minimum
      Standards for Health Sciences Libraries in Hospitals." In 1990, professional
      librarians were added to the survey team and, later, to the CSMS CME Committee.
      Librarians participating in this effort are recruited from the membership of the
      Connecticut Association of Health Sciences Librarians (CAHSL). The positive
      results of having a qualified librarian on the survey team and the invaluable
      impact of adherence to the MLA standards are outlined. As a direct result of this
      process, hospitals throughout the state have added staffing, increased space, and
      added funding for resources during an era of cutbacks. Some hospital libraries
      have been able to maintain a healthy status quo, while others have had proposed
      cuts reconsidered by administrators for fear of losing valuable CME accreditation
      status. Creating a relationship with an accrediting agency is one method by which
      hospital librarians elsewhere may strengthen their efforts to ensure adequate
      library resources in an era of downsizing. In addition, this collaboration has
      provided a new and important role for librarians to play on an accreditation
      team.

PMID- 11465687
TI  - A medical book collection for physician assistants.
AB  - Selecting resources for physician assistants is challenging and can be
      overwhelming. Although several core lists exist for nursing, allied health, and
      medical libraries, judging the scope and level of these resources in relation to
      the information needs of the physician assistant is difficult. Medical texts can
      be highly specialized and very expensive, in essence, "overkill" for the needs of
      the physician assistant. This bibliography is meant to serve as a guide to
      appropriate medical texts for physician assistants. Titles were selected from the
      Brandon/Hill list, Doody's Electronic Journal, and various other reference
      resources. Resources were evaluated based on the subject and scope, audience,
      authorship, cost, and currency. The collection includes 195 titles from 33
      specialty areas. Standard texts in each area are also included.

PMID- 11465688
TI  - Health sciences libraries in Kuwait: a study of their resources, facilities, and
      services.
AB  - The purpose of this study was to examine the current status of health sciences
      libraries in Kuwait in terms of their staff, collections, facilities, use of
      information technology, information services, and cooperation. Seventeen
      libraries participated in the study. Results show that the majority of health
      sciences libraries were established during the 1980s. Their collections are
      relatively small. The majority of their staff is nonprofessional. The majority of
      libraries provide only basic information services. Cooperation among libraries is
      limited. Survey results also indicate that a significant number of health
      sciences libraries are not automated. Some recommendations for the improvement of
      existing resources, facilities, and services are made.

PMID- 11465689
TI  - Bundles: meeting clinical information needs.

PMID- 11465690
TI  - The use of Dublin Core metadata in a structured health resource guide on the
      internet.

PMID- 11465691
TI  - Publishers.

PMID- 11465692
TI  - Mergers in the publishing industry.

PMID- 11465693
TI  - Note to "Ethics and Access to Teaching Material in the Medical Library: The Case
      of the Pernkopf Atlas".

PMID- 11465694
TI  - The laboratory as library metaphor and some reflections on professional practice.

PMID- 11465695
TI  - Carol G. Jenkins, Medical Library Association President 2001-2002.

PMID- 11465696
TI  - The verdict favors nonsteroidal antiinflammatory drugs for treatment of
      osteoarthritis and a plea for more evidence on other treatments.

PMID- 11465697
TI  - Interleukin-18: a novel cytokine in inflammatory rheumatic disease.

PMID- 11465698
TI  - Classification of anti-endothelial cell antibodies into antibodies against
      microvascular and macrovascular endothelial cells: the pathogenic and diagnostic
      implications.

PMID- 11465699
TI  - Recommendations for the prevention and treatment of glucocorticoid-induced
      osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on
      Glucocorticoid-Induced Osteoporosis.
AB  - Glucocorticoid-induced bone loss should be prevented, and if present, should be
      treated (Table 2). Supplementation with calcium and vitamin D at a dosage of 800
      IU/day, or an activated form of vitamin D (e.g., alfacalcidiol at 1 microg/day or
      calcitriol at 0.5 microg/day), should be offered to all patients receiving
      glucocorticoids, to restore normal calcium balance. This combination has been
      shown to maintain bone mass in patients receiving long-term low-to-medium-dose
      glucocorticoid therapy who have normal levels of gonadal hormones. However, while
      supplementation with calcium and vitamin D alone generally will not prevent bone
      loss in patients in whom medium-to-high-dose glucocorticoid therapy is being
      initiated, supplementation with calcium and an activated form of vitamin D will
      prevent bone loss. There are no data available to support any conclusion about
      the antifracture efficacy of the combination of calcium supplementation plus an
      activated form of vitamin D. Antiresorptive agents are effective in the treatment
      of glucocorticoid-induced bone loss. All of these agents either prevent bone loss
      or modestly increase lumbar spine bone mass and maintain hip bone mass. While
      there are no randomized controlled trials of prevention of glucocorticoid-induced
      bone loss or radiographic vertebral fracture outcomes with HRT or testosterone,
      patients receiving long-term glucocorticoid therapy who are hypogonadal should be
      offered HRT. The bisphosphonates are effective for both the prevention and the
      treatment of glucocorticoid-induced bone loss. Large studies have demonstrated
      that bisphosphonates also reduce the incidence of radiographic vertebral
      fractures in postmenopausal women with glucocorticoid-induced osteoporosis.
      Treatment with a bisphosphonate is recommended to prevent bone loss in all men
      and postmenopausal women in whom long-term glucocorticoid treatment at > or =5
      mg/day is being initiated, as well as in men and postmenopausal women receiving
      long-term glucocorticoids in whom the BMD T-score at either the lumbar spine or
      the hip is below normal. While there is little information on the prevention or
      treatment of bone loss in premenopausal women, these women, too, may lose bone
      mass if they are being treated with glucocorticoids, so prevention of bone loss
      with antiresorptive agents should be considered. If bisphosphonate therapy is
      being considered for a premenopausal woman, she must be counseled regarding use
      of appropriate contraception. The therapies to prevent or treat glucocorticoid
      induced bone loss should be continued as long as the patient is receiving
      glucocorticoids. Data from large studies of anabolic agents (e.g., PTH) and
      further studies of combination therapy in patients receiving glucocorticoids are
      eagerly awaited so additional options will be available for the prevention of
      this serious complication of glucocorticoid treatment.

PMID- 11465700
TI  - Is rheumatoid arthritis care more costly when provided by rheumatologists
      compared with generalists?
AB  - OBJECTIVE: Controversy surrounds the cost-effectiveness of rheumatologist care
      compared with generalist care for patients with rheumatoid arthritis (RA).
      Rheumatologists can provide 2 distinct types of care for RA patients: primary
      care and specialist care. We sought to examine the relationship between cost and
      type of care in a population-based cohort of patients with RA. METHODS: Data
      regarding specialty of care and use of health services (i.e., total direct
      medical costs, surgeries, radiographs, laboratory tests, hospital days) were
      collected from a community sample of 249 patients with RA (defined using the 1987
      American College of Rheumatology diagnostic criteria) among Rochester, Minnesota
      residents > or =35 years of age. In a randomly selected subset of 99 of these RA
      patients, detailed information on all physician encounters was collected and
      categorized according to whether or not the care received constituted "primary
      care" according to the Institute of Medicine definition. Using these data, we
      evaluated the influence of type of care as well as specialty of provider on
      utilization. For these analyses, total direct costs included all inpatient and
      outpatient health care costs incurred by all local providers (excluding
      outpatient prescription drugs). RESULTS: The 249 patients with RA (mean age 64
      years, 75% women) were followed up for a median of 5.4 years, while the subset of
      99 RA patients (mean age 64 years, 77% women) were followed up for a median of
      4.7 years. The overall median direct medical costs per person per year were
      $2,749 and $2,929 for the total cohort and for the subset of 99 patients,
      respectively. Generalized linear regression analyses (considering all visits of
      the 249 RA patients) revealed that after adjusting for demographics and disease
      characteristics, rheumatologist care (compared with nonrheumatologist care) was
      not associated with higher total direct medical costs (P = 0.85) or more hospital
      days (P = 0.35), but was associated with slightly more radiographs (P = 0.037)
      and significantly more laboratory tests (P < 0.0001). When considering only
      primary care, such care by rheumatologists was, again, not associated with higher
      total direct medical costs (P = 0.11) or more hospital days (P = 0.69) or more
      laboratory tests (P = 0.54), but was associated with slightly more radiographs (P
      = 0.035). CONCLUSION: Rheumatologist care is not more costly than generalist care
      for patients with RA. Important differences (especially in the use of laboratory
      tests) become apparent when the type of care provided as well as the specialty of
      the provider are considered in the analyses.

PMID- 11465701
TI  - Effect of folic or folinic acid supplementation on the toxicity and efficacy of
      methotrexate in rheumatoid arthritis: a forty-eight week, multicenter,
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To study the effect of folates on discontinuation of methotrexate
      (MTX) as single-drug antirheumatic treatment due to toxicity, to determine which
      type of adverse events are reduced, to study the effects on the efficacy of MTX,
      and to compare folic with folinic acid supplementation in a 48-week, randomized,
      double-blind, placebo-controlled trial. METHODS: Patients with active RA (n =
      434) were randomly assigned to receive MTX plus either placebo, folic acid (1
      mg/day), or folinic acid (2.5 mg/week). The initial MTX dosage was 7.5 mg/week;
      dosage increases were allowed up to a maximum of 25 mg/week for insufficient
      responses. Folate dosages were doubled once the dosage of MTX reached 15 mg/week.
      The primary end point was MTX withdrawal because of adverse events. Secondary end
      points were the MTX dosage and parameters of efficacy and toxicity of MTX.
      RESULTS: Toxicity-related discontinuation of MTX occurred in 38% of the placebo
      group, 17% of the folic acid group, and 12% of the folinic acid group. These
      between-group differences were explained by a decreased incidence of elevated
      liver enzyme levels in the folate supplementation groups. No between-group
      differences were found in the frequency of other adverse events or in the
      duration of adverse events. Parameters of disease activity improved equally in
      all groups. Mean dosages of MTX at the end of the study were lower in the placebo
      group (14.5 mg/week) than in the folic and folinic acid groups (18.0 and 16.4
      mg/week, respectively). CONCLUSION: Both folate supplementation regimens reduced
      the incidence of elevated liver enzyme levels during MTX therapy, and as a
      consequence, MTX was discontinued less frequently in these patients. Folates seem
      to have no effect on the incidence, severity, and duration of other adverse
      events, including gastrointestinal and mucosal side effects. Slightly higher
      dosages of MTX were prescribed to obtain similar improvement in disease activity
      in the folate supplementation groups.

PMID- 11465702
TI  - Treatment of rheumatoid arthritis with total lymphoid irradiation: long-term
      survival.
AB  - OBJECTIVE: Total lymphoid irradiation (TLI) has been used to treat rheumatoid
      arthritis (RA) since the 1970s. This study reviews long-term (15-20-year)
      mortality outcomes of patients treated with TLI for RA at Stanford University
      Medical Center and compares these outcomes with those in patients treated with
      disease-modifying antirheumatic drugs (DMARDs). METHODS: Fifty-three patients
      with RA were treated with full-dose TLI at Stanford University Medical Center.
      All had failed previous therapy with gold salts and penicillamine. One hundred
      six control patients were selected from the Arthritis, Rheumatism, and Aging
      Medical Information Systems database and were matched with the patients for age,
      sex, disease duration, and mean Health Assessment Questionnaire (HAQ) score.
      Survival was analyzed using Kaplan-Meier methods and Cox proportional hazards
      regression. RESULTS: No significant difference in age and sex was found between
      TLI-treated patients and controls. TLI-treated patients had more education (mean
      13.4 years versus 11.8 years; P = 0.016) and received more DMARDs prior to TLI
      (mean 2.1 versus 1.3; P = 0.0001). TLI-treated patients had lower mean HAQ scores
      at the time of TLI (2.0 versus 2.4; P = 0.0002). TLI had no significant overall
      effect on survival in treated patients compared with controls (P = 0.62). The
      survival curves appeared to cross over at approximately 11 years of followup,
      with better early survival in the TLI group and better late survival in the
      control group. There was a total of 25 deaths in the TLI group. There were 45
      deaths in the control group, with causes of death available for 20 patients.
      There were 3 patients with lymphoma and 2 with myelodysplastic syndrome in the
      TLI group, and none in the control group. The most common cause of death in both
      groups was infection. CONCLUSION: TLI had no significant effect on overall
      survival, with trends toward higher early mortality in controls and trends toward
      higher late mortality in TLI-treated patients. Overall, there was no difference
      in mortality, but it appears that there may have been more lymphoproliferative
      malignancies in the TLI cohort. We would recommend that TLI be used cautiously
      for patients with refractory RA in whom the benefits outweigh the risks.

PMID- 11465703
TI  - Independent association of rheumatoid factor and the HLA-DRB1 shared epitope with
      radiographic outcome in rheumatoid arthritis.
AB  - OBJECTIVE: Findings of a recent study suggested that HLA-DRB1 alleles encoding
      the rheumatoid arthritis (RA) "shared epitope" (SE) were not predictive of
      erosive damage at 2 years in patients with early inflammatory arthritis who were
      rheumatoid factor (RF) positive, but were predictive in those who were RF
      negative. The present study was undertaken to determine whether RF status was
      also important in the association between the SE and radiographic outcome in
      patients with longstanding RA. METHODS: The association between radiographic
      outcome, HLA-DRBI, and RF status was examined in 299 RA patients with established
      disease (5-30 years). Radiographic outcome was measured by scoring radiographs of
      the hands and feet using the standard radiographs of Larsen. HLA-DRB1 typing was
      performed using polymerase chain reaction methodology. Results were stratified by
      RF status and analyzed by multiple regression. RESULTS: An association between
      radiographic severity and the SE was found in RF-, but not RF+, patients. RF-
      patients carrying an SE allele had higher Larsen scores than RF- patients lacking
      the SE, although there was no association with SE dosage. The mean Larsen score
      was significantly higher in RF+ patients than in RF- patients, but there were no
      differences between RF+ patients with 0, 1, or 2 SE alleles. Multiple regression
      analysis confirmed independent associations of RF and SE positivity with
      radiographic outcome. No significant associations were found between RF and the
      SE, or RF and individual SE alleles. CONCLUSION: Our data indicate that RF and
      the SE are independently associated with radiographic outcome in RA. In RF+
      patients with longstanding RA, there is no apparent association between the
      presence of the SE and radiographic damage. However, in RF-patients, although
      radiographic outcome is generally less severe, there is an association between
      severity and presence of the SE.

PMID- 11465704
TI  - Localization of 3-nitrotyrosine to rheumatoid and normal synovium.
AB  - OBJECTIVE: To determine the localization of 3-nitrotyrosine (3-NT), a footprint
      marker of peroxynitrite (ONOO-) and other reactive nitrogen species, to the
      inflamed human synovium and to compare this with normal synovial and nonsynovial
      tissue of human and animal origin. METHODS: Monoclonal and polyclonal antibodies
      were used to investigate for 3-NT, inducible nitric oxide synthase (iNOS),
      macrophage marker CD68, and the vascular smooth muscle marker alpha-actin by
      avidin-biotin immunocytochemistry. RESULTS: In the inflamed synovium, 3-NT was
      found in the vascular smooth muscle and macrophages. In normal human synovium, 3
      NT was present in the vascular smooth muscle and some lining cells and was not
      associated with immunoreactivity for iNOS. Similarly, 3-NT could be demonstrated
      in the vascular smooth muscle cells of normal rats and iNOS knockout mice. It was
      not present in the vascular smooth muscle of healthy, nonsynovial tissue.
      CONCLUSION: The synovial vasculature in histologically normal human and naive
      rodent synovium was alone among the normal tissues studied in exhibiting iNOS
      independent immunoreactivity for 3-NT. These findings suggest a physiologic role
      for ONOO- in normal synovial vascular function.

PMID- 11465705
TI  - Expression of hypoxia-inducible factor 1alpha by macrophages in the rheumatoid
      synovium: implications for targeting of therapeutic genes to the inflamed joint.
AB  - OBJECTIVE: To determine if the rheumatoid synovium is a suitable target for
      hypoxia-regulated gene therapy. METHODS: Sequential sections of wax-embedded
      synovial membrane samples were obtained from 10 patients with rheumatoid
      arthritis (RA), 10 with primary osteoarthritis (OA), and from 6 healthy controls.
      Membrane sections from each patient were immunostained for hypoxia-inducible
      factor 1alpha (HIF-1alpha) and CD68 (a pan-macrophage marker). RESULTS: HIF
      1alpha was expressed abundantly by macrophages in most rheumatoid synovia,
      predominantly close to the intimal layer but also in the subintimal zone. There
      was markedly lower expression of HIF-1alpha in OA synovia, and it was absent from
      all of the healthy synovia. CONCLUSION: These observations indicate that
      macrophages transduced with a therapeutic gene under the control of a hypoxia
      inducible promoter could be administered to RA patients systemically. Migration
      of these cells to synovial tissue would result in the transgene being switched on
      in diseased joints but not in healthy tissues.

PMID- 11465706
TI  - Role of Notch-1 intracellular domain in activation of rheumatoid synoviocytes.
AB  - OBJECTIVE: Notch family proteins are transmembrane receptors that control cell
      fate and proliferation. Rheumatoid arthritis (RA) is characterized by activation
      and abnormal proliferation/differentiation of synoviocytes. We examined the
      expression of Notch-1 and its role in the activation of RA synoviocytes. METHODS:
      The expression of Notch-1 protein was detected by a specific antibody raised
      against the Notch-1 intracellular domain. Notch-1 messenger RNA (mRNA) expression
      in synoviocytes was analyzed by Northern blotting. Notch-1 protein expression was
      confirmed by Western blotting with anti-Notch-1 antibody. To analyze the role of
      Notch-1 in synoviocyte proliferation, we examined the effects of antisense Notch
      1 oligonucleotides (ODNs) and MW167, a gamma-secretase inhibitor. RESULTS: Notch
      1 protein and mRNA were detected in synovium from all study subjects. The nucleus
      of RA synoviocytes showed strong staining with anti-Notch-1 antibody, whereas
      there was predominantly cytoplasmic staining of normal and osteoarthritis (OA)
      synoviocytes. Western blotting showed a distinct approximately 63-kd protein
      detected by anti-Notch-1 antibody in nuclear extracts from RA synoviocytes,
      indicating that nuclear staining of RA synovium and synoviocytes is likely to be
      the result of nuclear localization of Notch-1 intracellular domain (NICD).
      Furthermore, tumor necrosis factor alpha (TNFalpha) increased NICD nuclear
      translocation in a dose-dependent manner. Antisense Notch-1 ODNs partially
      blocked the proliferation of RA synoviocytes and inhibited TNFalpha-induced
      proliferation in both OA and RA synoviocytes. In addition, gamma-secretase
      inhibitor, which blocks the production of NICD, also inhibited TNFalpha-induced
      proliferation of RA synoviocytes. CONCLUSION: Our results demonstrate the
      expression of Notch-1 in synoviocytes and the presence of Notch-1 fragment in the
      nuclei of RA synoviocytes and suggest the involvement of Notch-1 signaling in the
      TNFalpha-induced proliferation of RA synoviocytes.

PMID- 11465707
TI  - Regulation of tumor necrosis factor alpha-mediated apoptosis of rheumatoid
      arthritis synovial fibroblasts by the protein kinase Akt.
AB  - OBJECTIVE: To determine if tumor necrosis factor alpha (TNFalpha)-driven
      proliferation of rheumatoid arthritis synovial fibroblasts (RASF) is associated
      with up-regulation of the activity of serine/threonine kinase B/Akt and with
      survival of RASF. METHODS: Staining of phosphorylated Akt was done using anti
      phosphorylated Thr308 Akt antibody. Levels of phosphorylated Akt were analyzed by
      Western blot and Akt activity was analyzed using a kinase assay. TUNEL staining
      was used to analyze the cytotoxicity of TNFalpha treatment or TNFalpha combined
      with either the Akt activity inhibitor wortmannin, an adenovirus expressing
      dominant-negative mutant (AdAkt-DN), or an adenovirus expressing phosphatase and
      tensin homolog deleted on chromosome 10 (AdPTEN). RESULTS: The levels of
      phosphorylated Akt were higher in RASF than in osteoarthritis synovial
      fibroblasts (OASF), as demonstrated by immunohistochemical staining, immunoblot
      analysis, and an Akt kinase assay. The levels of phosphorylated Akt and Akt
      kinase activity were increased by stimulation of primary RASF with TNFalpha (10
      ng/ml). Treatment of RASF with the phosphatidylinositol 3-kinase inhibitor
      wortmannin (50 nM) plus TNFalpha resulted in apoptosis of 60 +/- 8% (mean +/-
      SEM) of RASF within 24 hours. This proapoptosis effect was specific for Akt,
      since equivalent levels of apoptosis were observed upon TNFalpha treatment of
      RASF transfected with AdAkt-DN and with AdPTEN, which opposes the action of Akt.
      CONCLUSION: These results indicate that phosphorylated Akt acts as a survival
      signal in RASF and contributes to the stimulatory effect of TNFalpha on these
      cells by inhibiting the apoptosis response. This effect was not observed in OASF
      and may reflect the pathophysiologic changes associated with the proliferating
      synovium in rheumatoid arthritis.

PMID- 11465708
TI  - Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant
      induced arthritis.
AB  - OBJECTIVE: To examine the expression of the novel CX3C chemokine fractalkine
      (Fkn) and its receptor (CX3CR1) in rheumatoid arthritis (RA) and rat adjuvant
      induced arthritis (AIA), a model of RA. METHODS: Immunohistochemistry, flow
      cytometry, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase
      polymerase chain reaction (RT-PCR), and chemotaxis assays were used. RESULTS: In
      rat AIA, synovial tissue (ST) macrophages, fibroblasts, endothelial cells, and
      dendritic cells were Fkn immunopositive, whereas lymphocytes did not
      significantly express Fkn. Significant staining for CX3CR1 was found in ST
      macrophages, fibroblasts, and dendritic cells, whereas only a small percentage of
      endothelial cells stained for CX3CR1 in rat AIA. We immunolocalized Fkn to RA ST
      macrophages, fibroblasts, endothelial cells, and dendritic cells. We also found
      intense ST macrophage and dendritic cell staining for CX3CR1 in RA ST. Flow
      cytometry analysis of RA synovial fluid (SF) and peripheral blood revealed a
      greater percentage of monocytes expressing Fkn and CX3CR1 compared with T cells.
      By ELISA, we found significantly elevated soluble Fkn (sFkn) levels in RA SF
      compared with SF from patients with osteoarthritis or other forms of arthritis.
      By RT-PCR, we found enhanced expression of Fkn and CX3CR1 mRNA on day 18 in rat
      AIA, a time of pronounced inflammation in the rat joint. Soluble Fkn-depleted RA
      SF showed significantly decreased chemotactic activity for monocytes compared
      with sham-depleted RA SF. CONCLUSION: These results indicate that Fkn and its
      receptor are both expressed in RA and in rat AIA, and that sFkn is up-regulated
      in RA SF. Furthermore, our data suggest a new role for Fkn in monocyte chemotaxis
      in the inflamed RA joint.

PMID- 11465709
TI  - Induction of an invasive phenotype by human parvovirus B19 in normal human
      synovial fibroblasts.
AB  - OBJECTIVE: To investigate the possible role of human parvovirus B19 as an
      etiologic agent in rheumatoid arthritis (RA), with particular emphasis on its
      ability to induce invasiveness in human synovial fibroblasts. METHODS: We
      established an experimental in vitro system in which normal primary human
      synovial fibroblasts were treated with or without parvovirus B19-containing human
      sera for 7 days. The fibroblasts were then tested for their ability to degrade
      reconstituted cartilage matrix using a well-characterized cartilage invasion
      assay system. RESULTS: Incubation with parvovirus B19-containing serum induced an
      invasive phenotype in normal human synovial fibroblasts. B19 serum-treated
      synovial fibroblasts exhibited an increase in invasion of up to 248% compared
      with the activity of fibroblasts in media alone, in contrast to B19-negative sera
      treated synovial fibroblasts, which exhibited no significant change compared with
      that in media alone. In addition, preincubation of viremic serum with a
      neutralizing antibody to B19 abrogated the observed effect. CONCLUSION: These
      results provide direct evidence regarding the ability of parvovirus B19 to induce
      invasive properties in normal human synovial fibroblasts. Parvovirus B19 has been
      proposed as an etiologic agent of RA, and our data provide the first biologic
      link between exposure to B19 and phenotypic changes in normal human synovial
      fibroblasts.

PMID- 11465710
TI  - A randomized, double-blind, crossover clinical trial of diclofenac plus
      misoprostol versus acetaminophen in patients with osteoarthritis of the hip or
      knee.
AB  - OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of
      diclofenac + misoprostol versus acetaminophen in ambulatory patients with
      osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care
      settings were eligible if they were age >40 years and if they had
      Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a
      score of > or =30 mm on a 100-mm visual analog pain scale. Patients were
      randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice
      daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then
      crossed over to the other treatment for 6 weeks. A placebo was included in each
      treatment regimen to enable double blinding. The primary outcome measures were
      the Western Ontario and McMaster Universities Osteoarthritis Index and the visual
      analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety
      was assessed using a standard form to review adverse events. RESULTS: We enrolled
      227 patients, of whom 218 provided data for the first treatment period and 181
      provided data for both treatment periods. Significantly higher levels of
      improvement in the primary outcomes were seen for diclofenac + misoprostol than
      for acetaminophen (P < 0.001). Adverse events were more common when patients took
      diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as
      "better" or "much better" by 57% of the 174 patients who provided such ratings
      for both treatment periods, while acetaminophen was rated as "better" or "much
      better" by 20% of these patients, and 22% reported no difference (P < 0.001).
      Differences favoring diclofenac + misoprostol over acetaminophen were greater in
      patients with more severe osteoarthritis according to baseline pain scores,
      radiographs, or number of involved joints. CONCLUSION: Patients with
      osteoarthritis of the hip or knee had significantly greater improvements in pain
      scores over 6 weeks with diclofenac + misoprostol than with acetaminophen,
      although patients with mild osteoarthritis had similar improvements with both
      drugs. Acetaminophen was associated with fewer adverse events.

PMID- 11465711
TI  - Stratification of flare intensity identifies placebo responders in a treatment
      efficacy trial of patients with osteoarthritis.
AB  - OBJECTIVE: Studies evaluating osteoarthritis treatment often use increased
      arthritis activity ("flare") as a selection criterion, although no standardized
      assessments are available to quantify flare intensity and little is known about
      how this criterion affects treatment comparisons. This study evaluated the
      reliability of a flare assessment and how pretreatment flare intensity impacts
      conclusions on treatment efficacy. METHODS: Using data from a double-blind,
      randomized, controlled trial (n = 182), we compared 3 osteoarthritis treatments
      with placebo in patients who met 3 of 4 flare criteria. The Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to
      document levels of pain, stiffness, and physical functioning at baseline and at
      the final visit. Following factor analytic evaluation, the flare items were
      standardized and summed to create a flare intensity index, which was used to
      identify patient subgroups. Analysis of covariance was applied to compare change
      in WOMAC scale scores from baseline to final visit for assessment of treatment
      differences among the flare intensity subgroups. RESULTS: The flare indicators
      appeared unidimensional. Analyses were stratified by tertiles of flare intensity.
      Mean WOMAC scores improved in the patients receiving active treatment who were
      categorized into the 2 lowest flare intensity subgroups, but mean WOMAC scores
      improved in patients in all 4 treatment groups (active and placebo) in the most
      intense flare subgroup. CONCLUSION: Patients with higher intensity flares may be
      more likely to report substantial improvement in functional status regardless of
      treatment. Failure to account for flare intensity in analyses of data from pain
      trials with flare-based designs may inflate the risk of Type I and Type II errors
      in the interpretation of study results.

PMID- 11465712
TI  - Molecular markers predictive of the capacity of expanded human articular
      chondrocytes to form stable cartilage in vivo.
AB  - OBJECTIVE: To establish a model and associated molecular markers for monitoring
      the capacity of in vitro-expanded chondrocytes to generate stable cartilage in
      vivo. METHODS: Adult human articular chondrocytes (AHAC) were prepared by
      collagenase digestion of samples obtained postmortem and were expanded in
      monolayer. Upon passaging, aliquots of chondrocyte suspensions were either
      injected intramuscularly into nude mice, cultured in agarose, or used for gene
      expression analysis. Cartilage formation in vivo was documented by histology,
      histochemistry, immunofluorescence for type II collagen, and proteoglycan
      analysis by 35S-sulfate incorporation and molecular sieve chromatography of the
      radiolabeled macromolecules. In situ hybridization for species-specific genomic
      repeats was used to discriminate human-derived from mouse-derived cells. Gene
      expression dynamics were analyzed by semiquantitative reverse transcription
      polymerase chain reaction. RESULTS: Intramuscular injection of freshly isolated
      AHAC into nude mice resulted in stable cartilage implants that were resistant to
      mineralization, vascular invasion, and replacement by bone. In vitro expansion of
      AHAC resulted in the loss of in vivo cartilage formation. This capacity was
      positively associated with the expression of fibroblast growth factor receptor 3,
      bone morphogenetic protein 2, and alpha1(II) collagen (COL2A1), and its loss was
      marked by the up-regulation of activin receptor-like kinase 1 messenger RNA.
      Anchorage-independent growth and the reexpression of COL2A1 in agarose culture
      were insufficient to predict cartilage formation in vivo. CONCLUSION: AHAC have a
      finite capacity to form stable cartilage in vivo; this capacity is lost
      throughout passaging and can be monitored using a nude mouse model and associated
      molecular markers. This cartilage-forming ability in vivo may be pivotal for
      successful cell-based joint surface defect repair protocols.

PMID- 11465713
TI  - Synergistic effects of glycoprotein 130 binding cytokines in combination with
      interleukin-1 on cartilage collagen breakdown.
AB  - OBJECTIVE: To determine whether other glycoprotein 130 (gp130) binding cytokines
      can mimic the effects of oncostatin M (OSM) in acting synergistically with
      interleukin-1alpha (IL-1alpha) to induce cartilage collagen breakdown and
      collagenase expression, and to determine which receptors mediate these effects.
      METHODS: The release of collagen and proteoglycan was assessed in bovine and
      human cartilage explant cultures. Messenger RNA (mRNA) and protein production
      from immortalized human chondrocytes (T/C28a4) was analyzed by Northern blotting
      and specific enzyme-linked immunosorbent assays. Collagenase activity was
      measured by bioassay. Cell surface receptors were detected by flow cytometry.
      RESULTS: OSM in combination with IL-1alpha caused a rapid synergistic induction
      of matrix metalloproteinase 1 mRNA, which was sustained over a 72-hour period.
      Flow cytometric analyses detected both the OSM-specific receptor and the gp130
      receptor at the chondrocyte cell surface, but failed to detect the leukemia
      inhibitory factor receptor (LIFR). Cartilage degradation assays revealed that, of
      the gp130 binding cytokines, only OSM and IL-6, in the presence of its soluble
      receptor (sIL-6R), were able to act synergistically with IL-1alpha to promote
      collagen release. CONCLUSION: This study demonstrates that IL-6 can mimic OSM in
      synergizing with IL-1alpha to induce chondrocyte-mediated cartilage collagen
      breakdown and collagenase production. In order to have this effect, IL-6 requires
      the presence of its soluble receptor. The apparent absence of LIFR explains why
      other gp130 binding cytokines do not act in synergy with IL-1alpha. Since OSM, IL
      6, and sIL-6R levels have all been shown to be elevated in the rheumatoid joint,
      our findings suggest that these cytokines may be key mediators of cartilage
      collagen catabolism in the inflammatory arthritides.

PMID- 11465714
TI  - Production of the chemokine RANTES by articular chondrocytes and role in
      cartilage degradation.
AB  - OBJECTIVE: To examine the expression of the chemokine RANTES and its receptors in
      normal and osteoarthritic (OA) human cartilage and to analyze its effects on
      chondrocyte function. METHODS: The expression of RANTES and its receptors were
      examined by reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. The effect of RANTES on gene expression of other cytokines
      and on the release of mediators of cartilage degradation was also examined by PCR
      and enzyme-linked immunosorbent assay. RESULTS: The expression of RANTES was
      undetectable in normal chondrocytes until after stimulation with interleukin
      1beta (IL-1beta) or IL-18. Cultures of normal cartilage also produced RANTES in
      response to IL-1beta, as demonstrated by immunohistochemistry. All OA cartilage
      samples analyzed expressed RANTES messenger RNA (mRNA); RANTES protein was
      detected by immunohistochemistry in the superficial and mid zones of the tissue.
      OA chondrocytes produced elevated levels of RANTES constitutively and after IL
      1beta stimulation. Normal cartilage expressed the RANTES receptors CCR3 and CCR5,
      but not CCR1. CCR1 was expressed in OA cartilage, and CCR3 and CCR5 were
      increased. In normal chondrocytes, RANTES induced the expression of inducible
      nitric oxide synthase and IL-6. RANTES stimulated the release of matrix
      metalloproteinase 1 in normal and OA chondrocytes as effectively as IL-1beta.
      Treatment of normal articular cartilage with RANTES increased the release of
      glycosaminoglycans and profoundly reduced the intensity of Safranin O staining.
      CONCLUSION: Chondrocytes produce RANTES and express RANTES receptors. RANTES and
      CCR5 were markedly increased in OA and after in vitro treatment of normal
      chondrocytes with IL-1. Chondrocyte activation and cartilage degradation were
      identified as novel biologic and pathogenetic activities of this chemokine.

PMID- 11465715
TI  - Regulation of CD95 (Fas/APO-1)-induced apoptosis in human chondrocytes.
AB  - OBJECTIVE: To examine the role of nuclear factor kappaB (NF-kappaB) and caspases
      3, 8, and 9 in CD95-mediated apoptosis of normal chondrocytes. METHODS: First
      passage chondrocytes from normal human knee cartilage were stimulated with CD95
      antibody, and cell death was determined by annexin V binding and by an enzyme
      linked immunosorbent assay. Activation of caspases 3, 8, and 9 was measured by
      Western blotting, and their role in death signaling was evaluated using caspase
      specific small peptide inhibitors. The influence of NF-kappaB was determined by
      electrophoretic mobility shift assay (EMSA) and proteasome inhibition-dependent
      blocking of the degradation of inhibitor of NF-kappaB. RESULTS: Low levels of NF
      kappaB activity were detected by EMSA in unstimulated chondrocytes. NF-kappaB
      activity was increased in response to agonistic CD95 antibody. CD95 antibody
      induced apoptosis was potentiated by the proteasome inhibitors MG-132 and PS1,
      and this was associated with a reduced nuclear translocation of NF-kappaB.
      Proteasome inhibitors also caused the induction of DNA fragmentation by tumor
      necrosis factor alpha. Procaspase 3 processing was enhanced by the proteasome
      inhibitor MG-132. Procaspase 8 was undetectable by immunoblotting in whole cell
      lysates of chondrocytes, but caspase 8 messenger RNA was detected by reverse
      transcription-polymerase chain reaction. Furthermore, apoptosis induced by CD95
      stimulation and proteasome inhibitors was blocked by the caspase 8-specific
      inhibitor Ac-IETD-CHO. Processing of procaspase 9 was not observed, and
      inhibition of CD95-dependent cell death by the caspase 9 inhibitor Ac-LEHD-CHO
      was not significant. CONCLUSION: These results suggest that CD95-dependent cell
      death is enhanced by NF-kappaB inhibition at and/or downstream of caspase 8
      activation and that caspase 9 activation is not involved in CD95-mediated
      apoptosis in chondrocytes.

PMID- 11465716
TI  - Autoreactive T cells to topoisomerase I in monozygotic twins discordant for
      systemic sclerosis.
AB  - OBJECTIVE: To examine T and B cell responses to topoisomerase I (topo I) in a
      monozygotic twin pair discordant for systemic sclerosis (SSc). METHODS: The
      peripheral blood T cell proliferative responses induced by topo I and in vitro
      anti-topo I antibody production in cultures of T and B cells were examined in an
      SSc patient with serum anti-topo I antibody and in her healthy monozygotic twin.
      Topo I-reactive T cell lines were generated from the twin pair and analyzed for
      antigenic specificity, major histocompatibility complex class II restriction, and
      T cell receptor (TCR) gene usage. RESULTS: T cell proliferative responses to topo
      I were detected in both the SSc patient and her healthy twin, although the
      kinetics of the T cell response were accelerated in the patient compared with the
      healthy twin. The estimated frequency of circulating topo I-reactive T cells was
      1/6,700 in the SSc patient and 1/39,000 in the healthy twin. Anti-topo I antibody
      production was observed in cultures of T and B cells from the SSc patient, but
      not in those from the healthy twin. When the cells from the twins were mixed in
      different combinations, T cells from the healthy twin did stimulate the SSc
      patient's B cells to produce anti-topo I antibody through a CD40-dependent
      mechanism. Topo I-reactive T cell lines generated from the twins had similar
      characteristics, including a CD4+ phenotype, restriction by HLA-DR, recognition
      of epitopes within amino acid residues 209-386 of topo I, and dominant usage of
      the TCR Vbeta20 gene segment. CONCLUSION: These results indicate that topo I
      reactive T cells were activated and clonally expanded in the SSc patient.
      However, there were no substantial differences in either phenotypic or functional
      properties of topo I-reactive T cells obtained from the SSc patient and those
      obtained from her healthy identical twin. It is likely, therefore, that the anti
      topo I antibody response in the SSc patient is induced by in vivo activation of
      topo I-reactive T cells derived from the normal T cell repertoire.

PMID- 11465717
TI  - Palliation of systemic sclerosis-associated pulmonary hypertension by atrial
      septostomy.
AB  - The onset of pulmonary hypertension in patients with systemic sclerosis carries a
      poor prognosis. Atrial septostomy has been used successfully to palliate endstage
      primary pulmonary hypertension but has not been attempted in other forms of
      pulmonary vascular disease. We report substantial clinical improvement following
      atrial septostomy in a patient with systemic sclerosis complicated by severe,
      isolated pulmonary hypertension. After the procedure, exercise capacity was
      improved and exertional syncope abolished. We suggest that this procedure should
      be considered for other patients with this diagnosis.

PMID- 11465718
TI  - Systemic sclerosis with renal crisis and pulmonary hypertension: a report of
      eleven cases.
AB  - OBJECTIVE: To describe a series of systemic sclerosis (SSc) patients with the
      unusual combination of scleroderma renal crisis (SRC) and pulmonary hypertension
      (PHT) without interstitial lung disease. METHODS: The medical records of 2,459
      SSc patients in the University of Pittsburgh Scleroderma Databank first evaluated
      between 1972 and 1999 were reviewed. RESULTS: Eleven patients (0.45%) had both
      SRC and PHT. All had been evaluated since 1979, when angiotensin-converting
      enzyme (ACE) inhibitor therapy for SRC became available. Seven had SSc with
      limited cutaneous involvement, and 4 had SSc with diffuse cutaneous involvement.
      SRC occurred first in all patients except 1, in whom the onsets of SRC and PHT
      were simultaneous. SRC preceded PHT by a mean of 4.3 years. Four patients had
      anti-Th/To antibody, 5 had anti-RNA polymerase III antibody, 2 had anti-U3 RNP
      antibody, and none had anticentromere or antitopoisomerase I antibody. Ten of the
      11 patients died, 8 from PHT. Ten patients were being treated with ACE inhibitor
      drugs when PHT developed. CONCLUSION: In SSc, SRC and PHT are not mutually
      exclusive complications. SSc patients surviving SRC who have serum antibodies to
      Th/To, RNA polymerase III, or U3 RNP are at increased risk to develop PHT. ACE
      inhibitor therapy did not prevent the development of PHT.

PMID- 11465719
TI  - Decreased susceptibility to Fas-induced apoptosis of systemic sclerosis dermal
      fibroblasts.
AB  - OBJECTIVE: To determine whether dysregulated apoptosis of systemic sclerosis
      (SSc) fibroblasts contributes to progressive fibrosis by promoting fibroblast
      longevity. METHODS: We examined the pattern of fibroblast proliferation and
      apoptosis in SSc skin lesions and the susceptibility of cultured SSc dermal
      fibroblasts to apoptosis. Skin biopsy samples from SSc patients and control
      subjects were used to establish fibroblast cultures and were examined
      histologically. In skin sections, apoptosis was examined by TUNEL, and
      proliferation by immunostaining for proliferating cell nuclear antigen.
      Susceptibility of fibroblasts to apoptosis induced in vitro by different stimuli
      was studied by TUNEL. Expression of Bcl-2, Bcl-x, and Bax proteins in cultured
      fibroblasts was studied by Western blotting. RESULTS: Proliferation of dermal
      fibroblasts was not observed in normal skin but was present in skin from patients
      with SSc and other inflammatory skin diseases. Apoptosis of fibroblasts in SSc
      fibrotic skin lesions was not observed. In vitro, SSc fibroblasts were
      specifically resistant to apoptosis induced by Fas receptor stimulation but had
      normal susceptibility to apoptosis induced by nonspecific stimuli (protein kinase
      inhibition or serum withdrawal). Decreased susceptibility to Fas stimulation was
      not caused by decreased levels of surface Fas receptor. In SSc fibroblasts,
      quiescence induced by confluence and serum starvation was followed by an abnormal
      down-regulation of proapoptotic Bax protein. Up-regulation of the Bax:Bcl-2 ratio
      in SSc fibroblasts by Bcl-2 antisense oligonucleotides restored their
      susceptibility to Fas-mediated apoptosis. CONCLUSION: Our findings suggest that
      abnormal apoptotic regulation in fibroblasts can contribute to the pathogenesis
      of progressive fibrosis in SSc. Modulation of Bcl-2-related proteins appears to
      be a potential target for the development of apoptosis-based antifibrotic
      strategies.

PMID- 11465720
TI  - Minimal alterations in the HLA-B27-bound peptide repertoire induced upon
      infection of lymphoid cells with Salmonella typhimurium.
AB  - OBJECTIVE: To characterize putative changes in the HLA-B27-bound peptide
      repertoire following infection of lymphoid cells with Salmonella typhimurium, a
      bacterium known to trigger reactive arthritis in HLA-B27-positive individuals.
      METHODS: A protocol was developed for efficient large-scale infection of
      lymphoblastoid cell transfectants expressing HLA-B*2705. HLA-B27-bound peptide
      pools were isolated from noninfected and infected B*2705+ cells and comparatively
      analyzed by high-performance liquid chromatography. Peptide-containing
      chromatographic fractions from noninfected and infected cells were systematically
      compared by mass spectrometry (MS) to look for putative differences at the level
      of individual peptides. RESULTS: The presence of B*2705 did not influence S
      typhimurium invasion, since this was equally efficient in nontransfected or B27
      transfected cells. The chromatographic profiles of B*2705-bound peptides from
      noninfected and infected cells were virtually identical. A total of 808 molecular
      species were compared by MS. Of these, 807 were present in both infected and
      noninfected cells. Only one molecular species from infected cells lacked a
      detectable counterpart in noninfected cells. CONCLUSION: Intracellular infection
      of lymphoid cells by S typhimurium induces minimal alterations in the HLA-B27
      bound peptide repertoire. Minor changes detectable by cytotoxic T lymphocytes,
      but not easily amenable to direct biochemical analysis, are not ruled out.

PMID- 11465721
TI  - Chromosomal DNA from a variety of bacterial species is present in synovial tissue
      from patients with various forms of arthritis.
AB  - OBJECTIVE: We and others have reported the presence of Chlamydia and other
      bacterial species in joint specimens from patients with reactive arthritis (ReA).
      The present study was conducted to investigate whether bacteria other than those
      specified by diagnostic criteria for ReA could be identified in synovial fluid
      (SF) or tissue from patients with various arthritides, and whether the presence
      of such organisms corresponds to particular clinical characteristics in any
      patient set or subset. METHODS: DNA in synovial biopsy samples and SF obtained
      from 237 patients with various arthritides, including ReA, rheumatoid arthritis,
      and undifferentiated oligoarthritis, was assayed by polymerase chain reaction
      (PCR) using "panbacterial" primers; we chose only samples known to be PCR
      negative for Chlamydia, Borrelia, and Mycoplasma species. PCR products were
      cloned, and cloned amplicons from each sample were sequenced; DNA sequences were
      compared against all others in GenBank for identification of bacterial species
      involved. RESULTS: Ten percent of patient samples were PCR positive in
      panbacterial screening assays. Bacterial species identified belonged to the
      genera Neisseria, Acinetobacter, Moraxella, Salmonella, Pseudomonas, and others.
      Thirty-five percent of PCR-positive patients showed the presence of DNA from more
      than a single bacterial species in synovium; overall, however, we could identify
      no clear relationship between specific single or multiple bacterial species in
      the synovium and any general clinical characteristics of any individual or group
      of patients. CONCLUSION: This analysis provides the first systematic attempt to
      relate bacterial nucleic acids in the synovium to clinical characteristics, joint
      findings, and outcomes. Many patients with arthritis have bacterial DNA in the
      joint, and, in some cases, DNA from more than a single species is present.
      However, except for 1 case of a control patient with staphylococcal septic
      arthritis, it is not clear from the present study whether the synovial presence
      of such organisms is related to disease pathogenesis or evolution in any or all
      cases.

PMID- 11465722
TI  - Antineutrophil cytoplasmic antibodies induce human monocytes to produce oxygen
      radicals in vitro.
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are believed to play a
      pathogenetic role in necrotizing small-vessel vasculitis. While the involvement
      of neutrophils in this disease has been extensively studied in vitro, we
      undertook to analyze thoroughly the contribution of monocytes to tissue
      destruction in systemic vasculitis. METHODS: Monocytes obtained from normal human
      individuals were stimulated by ANCA isolated from patients with active
      vasculitis. The formation of oxygen radicals was measured by a fluorometric assay
      using 2',7'-dichlorofluorescin diacetate. RESULTS: ANCA induced monocytes to
      produce oxygen radicals, resulting in a mean 43% increase (range 21-84%) in
      oxygen radical formation compared with normal IgG. The formation of reactive
      oxygen species was time and concentration dependent and was also induced by ANCA
      F(ab')2 fragments. Normal nonspecific IgG or their corresponding F(ab')2
      fragments induced no release or very little release of oxygen radicals.
      Preincubation of monocytes with the Fcy receptor type II-blocking monoclonal
      antibody IV.3 before addition of ANCA greatly reduced formation of oxygen
      radicals. Using ligand affinity chromatography with proteinase 3 (PR3) and
      myeloperoxidase (MPO), ANCA were further purified by depletion of patient IgG.
      The stimulation of monocytes with these pure PR3- and MPO-ANCA confirmed that
      cellular activation was specifically induced by ANCA. CONCLUSION: These results
      show that ANCA induce the formation of reactive oxygen species in human
      monocytes. These findings support the notion that ANCA specifically activate
      monocytes by several mechanisms to participate in the inflammatory process of
      ANCA-associated vasculitis.

PMID- 11465723
TI  - Oligoclonal B lymphocyte expansion in the synovium of a patient with Behcet's
      disease.
AB  - OBJECTIVE: Plasma cell infiltration is observed in recurrent arthritis associated
      with Behcet's disease (BD). The immune mechanism underlying B lymphocyte
      proliferation in the synovium is unclear. One hypothesis involves nonspecific
      polyclonal activation and another involves antigen-driven activation. The present
      study was undertaken to test both hypotheses and identify immunoglobulin genes
      that are clonally expanded in the synovium. METHODS: Peripheral blood lymphocytes
      (PBL) and synovial cells from a patient with BD and PBL from a healthy control
      subject were obtained. Complementarity-determining region 3 (CDR3) fingerprinting
      analysis and nucleotide sequence analysis of Ig transcripts derived from clonally
      expanded B lymphocytes were performed in parallel. RESULTS: Of 44 mu heavy chain
      clones of the VH4 family identified in the synovial tissue from the BD patient, 8
      clones showed identical nucleotide sequences, and therefore, 18.2% were clonally
      expanded. For y heavy chain, 4 of 50 clones of the VH3 family showed nearly
      identical sequences; therefore, 4-8% were clonally expanded. The kappa light
      chain did not show a dominant band, but a clone with a 12-amino acid CDR3 showed
      3% clonal expansion. Somatic mutations were frequently observed, with a high
      ratio of replacement to silent mutations in the CDRs compared with the framework
      regions. Three Ig genes expressed in the clonally expanded B lymphocytes were
      derived from germline gene segments reported to be involved in the production of
      autoantibodies. CONCLUSION: These results support the hypothesis that antigen
      driven clonal B lymphocyte proliferation occurs in the synovium in BD.
      Immunoglobulin transcripts clonally expanded in the synovium were identified.

PMID- 11465724
TI  - Orbital mucosa-associated lymphoid tissue (MALT)-type lymphoma in a patient with
      relapsing polychondritis.
AB  - Relapsing polychondritis is characterized by recurrent inflammation of the
      cartilaginous tissues of the ears, nose, peripheral joints, and the
      tracheobronchial tree. The eye is also a frequent target organ in relapsing
      polychondritis, and proptosis is a well-recognized manifestation of eye
      involvement. Similar to other rheumatologic diseases, an association of relapsing
      polychondritis with malignancy has been reported. We describe a patient with
      relapsing polychondritis who presented with exophthalmos. When treatment directed
      toward control of her underlying disease was only partially effective, further
      investigation revealed that she had an orbital mucosa-associated lymphoid tissue
      (MALT)-type B cell lymphoma. We hypothesize that the lymphoma resulted from
      malignant transformation of the relapsing polychondritis-induced inflammatory
      pseudotumor and emphasize that neoplastic disease should be considered in the
      differential diagnosis in patients with relapsing polychondritis presenting with
      exophthalmos.

PMID- 11465725
TI  - Interleukin-18 as a novel diagnostic marker and indicator of disease severity in
      adult-onset Still's disease.

PMID- 11465726
TI  - Serum sickness secondary to treatment with the murine-human chimeric antibody
      IDEC-C2B8 (rituximab).

PMID- 11465727
TI  - Area under the curve for the American College of Rheumatology improvement
      criteria: a valid addition to existing criteria in rheumatoid arthritis?

PMID- 11465728
TI  - Role of tumor necrosis factor alpha and potential benefit of tumor necrosis
      factor blockade treatment in systemic lupus erythematosus: comment on the
      editorial by Pisetsky.

PMID- 11465729
TI  - Gene function. Part 2.

PMID- 11465730
TI  - Protein structure prediction in genomics.
AB  - As the number of completely sequenced genomes rapidly increases, including now
      the complete Human Genome sequence, the post-genomic problems of genome-scale
      protein structure determination and the issue of gene function identification
      become ever more pressing. In fact, these problems can be seen as interrelated in
      that experimentally determining or predicting or the structure of proteins
      encoded by genes of interest is one possible means to glean subtle hints as to
      the functions of these genes. The applicability of this approach to gene
      characterisation is reviewed, along with a brief survey of the reliability of
      large-scale protein structure prediction methods and the prospects for the
      development of new prediction methods.

PMID- 11465731
TI  - Analysis and comparison of metabolic pathway databases.
AB  - Enormous amounts of data result from genome sequencing projects and new
      experimental methods. Within this tremendous amount of genomic data 30-40 per
      cent of the genes being identified in an organism remain unknown in terms of
      their biological function. As a consequence of this lack of information the
      overall schema of all the biological functions occurring in a specific organism
      cannot be properly represented. To understand the functional properties of the
      genomic data more experimental data must be collected. A pathway database is an
      effort to handle the current knowledge of biochemical pathways and in addition
      can be used for interpretation of sequence data. Some of the existing pathway
      databases can be interpreted as detailed functional annotations of genomes
      because they are tightly integrated with genomic information. However,
      experimental data are often lacking in these databases. This paper summarises a
      list of pathway databases and some of their corresponding biological databases,
      and also focuses on information about the content and the structure of these
      databases, the organisation of the data and the reliability of stored information
      from a biological point of view. Moreover, information about the representation
      of the pathway data and tools to work with the data are given. Advantages and
      disadvantages of the analysed databases are pointed out, and an overview to
      biological scientists on how to use these pathway databases is given.

PMID- 11465732
TI  - A comparison of microarray databases.
AB  - Microarray technology has become one of the most important functional genomics
      technologies. A proliferation of microarray databases has resulted. It can be
      difficult for researchers exploring this technology to know which bioinformatics
      systems best meet their requirements. In order to obtain a better understanding
      of the available systems, a survey and comparative analysis of microarray
      databases was undertaken. The survey included databases that are currently
      available, as well as databases that should become available in early 2001.
      Databases fall into three categories: (i) those that can be installed locally,
      (ii) those available for public data submission and (iii) those available for
      public query. Developers of microarray gene-expression databases were asked
      questions regarding the scope and availability of their database, its system
      requirements, its future compliance with MGED (Microarray Gene Expression
      Database) standards, and its associated analytical tools. Participants included
      AMAD (Stanford/Berkeley/UCSF), ArrayExpress (EBI), ChipDB (MIT/Whitehead), GeneX
      (NCGR), GeNet (Silicon Genetics), GeneDirector (BioDiscovery), GEO (NCBI), GXD
      (Jackson Laboratory), mAdb (NCI), maxdSQL (University of Manchester), NOMAD
      (UCSF), RAD (University of Pennsylvania) and SMD (Stanford University). Other
      database developers were contacted but data was not available at the time of
      manuscript preparation. Each database fulfils a different role, reflecting the
      widely varying needs of microarray users.

PMID- 11465733
TI  - The Edinburgh Mouse Atlas: using the CD.
AB  - This paper provides a simple introduction to the reconstructions and data
      handling tools stored on the Edinburgh Mouse Atlas CD, together with some of the
      ways in which the viewers and software can be used to understand mouse
      development and analyse data. The key aspect of the Mouse Atlas is that the
      underlying models are a complete representation of the histology, which has not
      been constrained to a particular interpretation. This means, for example, that
      the current anatomy domains can be further subdivided as required to any
      resolution up to the resolution of the models (2-7 microm). In the CD of the
      early embryos described here, virtually all tissues that can be usefully
      distinguished either by the histology or morphologically have been delineated.

PMID- 11465734
TI  - Large-scale production of mouse phenotypes: the search for animal models for
      inherited diseases in humans.
AB  - This paper is aimed principally at bioinformaticians and biologists as an
      introduction to recent advances in mouse mutagenesis, concentrating on genome
      wide screens utilising the powerful mutagen N-ethyl-N-nitroso-urea (ENU). It
      contains a brief background to the underlying genetics as well as details of the
      practical aspects of organisation and data capture for such projects.

PMID- 11465735
TI  - On the parallelisation of bioinformatics applications.
AB  - This paper surveys the computational strategies followed to parallelise the most
      used software in the bioinformatics arena. The studied algorithms are
      computationally expensive and their computational patterns range from regular,
      such as database-searching applications, to very irregularly structured patterns
      (phylogenetic trees). Fine- and coarse-grained parallel strategies are discussed
      for these very diverse sets of applications. This overview outlines computational
      issues related to parallelism, physical machine models, parallel programming
      approaches and scheduling strategies for a broad range of computer architectures.
      In particular, it deals with shared, distributed and shared/distributed memory
      architectures.

PMID- 11465736
TI  - Swiss-PDB Viewer (Deep View).

PMID- 11465737
TI  - Functional mapping of human medial frontal motor areas. The combined use of
      functional magnetic resonance imaging and cortical stimulation.
AB  - Two functional brain-mapping techniques, functional magnetic resonance imaging
      (fMRI) and cortical stimulation by chronically implanted subdural electrodes,
      were used in combination for presurgical evaluation of three patients with
      intractable, partial motor seizures. Brain mapping was focused on characterizing
      motor-related areas in the medial frontal cortex, where all patients had organic
      lesions. Behavioral tasks for fMRI involved simple finger and foot movements in
      all patients and mental calculations in one of them. These tasks allowed us to
      discriminate several medial frontal motor areas: the presupplementary motor areas
      (pre-SMA), the somatotopically organized SMA proper, and the foot representation
      of the primary motor cortex. All patients subsequently underwent cortical
      stimulation through subdural electrodes placed onto the medial hemispheric wall.
      In each patient, the cortical stimulation map was mostly consistent with that
      patient's brain map by fMRI. By integrating different lines of information, the
      combined fMRI and cortical stimulation map will contribute not only to safe and
      effective surgery but also to further understanding of human functional
      neuroanatomy.

PMID- 11465738
TI  - Perception of tilt (somatogravic illusion) in response to sustained linear
      acceleration during space flight.
AB  - During the 1998 Neurolab mission (STS-90), four astronauts were exposed to
      interaural and head vertical (dorsoventral) linear accelerations of 0.5 g and 1 g
      during constant velocity rotation on a centrifuge, both on Earth and during
      orbital space flight. Subjects were oriented either left-ear-out or right-ear-out
      (Gy centrifugation), or lay supine along the centrifuge arm with their head off
      axis (Gz centrifugation). Pre-flight centrifugation, producing linear
      accelerations of 0.5 g and 1 g along the Gy (interaural) axis, induced illusions
      of roll-tilt of 20 degrees and 34 degrees for gravito-inertial acceleration (GIA)
      vector tilts of 27 degrees and 45 degrees , respectively. Pre-flight 0.5 g and 1
      g Gz (head dorsoventral) centrifugation generated perceptions of backward pitch
      of 5 degrees and 15 degrees , respectively. In the absence of gravity during
      space flight, the same centrifugation generated a GIA that was equivalent to the
      centripetal acceleration and aligned with the Gy or Gz axes. Perception of tilt
      was underestimated relative to this new GIA orientation during early in-flight Gy
      centrifugation, but was close to the GIA after 16 days in orbit, when subjects
      reported that they felt as if they were 'lying on side'. During the course of the
      mission, inflight roll-tilt perception during Gy centrifugation increased from 45
      degrees to 83 degrees at 1 g and from 42 degrees to 48 degrees at 0.5 g. Subjects
      felt 'upside-down' during in-flight Gz centrifugation from the first in-flight
      test session, which reflected the new GIA orientation along the head dorsoventral
      axis. The different levels of in-flight tilt perception during 0.5 g and 1 g Gy
      centrifugation suggests that other non-vestibular inputs, including an internal
      estimate of the body vertical and somatic sensation, were utilized in generating
      tilt perception. Interpretation of data by a weighted sum of body vertical and
      somatic vectors, with an estimate of the GIA from the otoliths, suggests that
      perception weights the sense of the body vertical more heavily early in-flight,
      that this weighting falls during adaptation to microgravity, and that the
      decreased reliance on the body vertical persists early post-flight, generating an
      exaggerated sense of tilt. Since graviceptors respond to linear acceleration and
      not to head tilt in orbit, it has been proposed that adaptation to weightlessness
      entails reinterpretation of otolith activity, causing tilt to be perceived as
      translation. Since linear acceleration during in-flight centrifugation was always
      perceived as tilt, not translation, the findings do not support this hypothesis.

PMID- 11465739
TI  - On the role of static and dynamic visual afferent information in goal-directed
      aiming movements.
AB  - Movement planning has been shown to be optimized when the participant is
      permitted to see his or her hand resting on the starting base prior to movement
      initiation. However, this proposition is opposed by contradictory results. In the
      present study, we wanted to determine whether these conflicting results were
      caused by procedural differences. The results showed that seeing one's hand on
      the starting base did not result in more accurate aiming movement than when this
      information was not available. However, lower aiming errors were found when one
      was asked to foveate the starting base and then the target prior to movement
      initiation, but only when no dynamic visual information was available during
      movement. When an aiming movement was performed while one's hand was visible in
      visual periphery, foveating the starting base or not prior to movement initiation
      did not modify aiming accuracy. These results suggest that gazing at the starting
      base and then at the target provides an eye-based representation of the movement
      to be performed that can be used by the CNS to plan a manual aiming movement.
      Information for better planning of the direction--but not the extent--dimension
      of an upcoming movement can also be derived from dynamic visual information
      available in peripheral vision.

PMID- 11465740
TI  - Attention to olfaction. A psychophysical investigation.
AB  - Olfaction is unique among the senses in that signals from the peripheral sensory
      receptors bypass the thalamus on their way to the cortex. The fact that olfactory
      stimuli are not gated by the thalamus has led some researchers to suggest that
      people may be unable to selectively direct their attention toward the olfactory
      modality. We examined this issue in an experiment where participants made speeded
      intensity (strong vs weak)-discrimination responses to an unpredictable sequence
      of olfactory and visual stimuli. Attention was directed to either olfaction or to
      vision by means of an informative cue that predicted the likely modality for the
      upcoming target on the majority of trials. Participants responded more rapidly
      when the target was presented in the expected rather than the unexpected
      modality, showing that people can selectively attend to olfaction.

PMID- 11465741
TI  - Contribution of tactile information to accuracy in pointing movements.
AB  - We examined the contribution of tactile cues to accuracy during point-to-point
      movements. We used a task in which the experimenter guided either the left or
      right hand of the subject to a spatial location during the reference movement.
      During the subsequent test movement subjects were asked to point with the right
      hand to the remembered location without vision. Subjects contacted the target
      with their fingertip either during the reference movement, both the reference and
      test movements, or neither movement (i.e., the fingertip was held above the
      target surface). To differentiate between the contribution of tactile and
      proximal deep pressure information, the left index finger was anesthetized in a
      subsequent experiment. When subjects contacted the surface with the fingertip of
      the reference hand alone, error in movement direction decreased. When subjects
      made fingertip contact during the reference and test movements, gain error also
      decreased. Anesthesia of the fingertip degraded accuracy, suggesting that tactile
      information, independent of information from proximal deep pressure receptors,
      influenced movement accuracy. Thus, tactile information contributed to accuracy
      in pointing movements. We suggest that forces at fingertip contact may provide
      information regarding the orientation of the finger and forearm in space, which
      is used to replicate final arm posture. In addition, tactile cues at the
      beginning and end of the movement may be used to scale movement amplitude.

PMID- 11465742
TI  - Postural reflexes evoked by tapping forehead and chest.
AB  - We investigated whether a tap with a reflex hammer to the forehead can elicit
      responses in the leg muscles and whether vestibular stimulation is the crucial
      prerequisite for eliciting these responses. We also measured the postural changes
      caused by the tap and by the compensatory, presumably reflex-like reactions of
      the subject. Tap-evoked activity of leg muscles was easily elicited during
      upright stance in normal subjects and was also seen in two subjects without
      vestibular function. The pattern of muscle activation clearly showed a
      counteraction to the tap-evoked perturbation of stance. Taps applied to the chest
      elicited similar reflexes. Since these two conditions imply a different
      activation of the vestibular apparatus, the vestibular input alone cannot account
      for the observed leg muscle reflexes. We suggest that multisensory reflex
      pathways that integrate vestibular and proprioceptive inputs account for these
      reflexes.

PMID- 11465743
TI  - Modulation of intracortical inhibition induced by low- and high-frequency
      repetitive transcranial magnetic stimulation.
AB  - We studied the changes of duration of subsequent silent periods (SPs) during
      repetitive magnetic stimulation (rTMS) trains of ten stimuli delivered at low (1
      Hz) and high (7 Hz) frequencies. The effects at different intensities of
      stimulation (motor threshold, MT, 115% and 130% above the MT) were also
      evaluated. rTMS was performed in eight healthy subjects with a figure-of-eight
      coil placed over the hand motor area. The SP was recorded from abductor pollicis
      brevis (APB) muscle during a voluntary contraction of 30% of maximum effort. rTMS
      at 1-Hz frequency progressively decreased the duration of SP, whereas an
      alternating pattern of smaller and larger values was observed during trains at 7
      Hz frequency and higher stimulus intensity. The findings show that rTMS changes
      the duration of cortical SPs; the effect is probably due to the modulation of
      intracortical inhibitory interneurons depending on the frequency and intensity of
      stimulation.

PMID- 11465744
TI  - The role of action in postural preparation for loading and unloading in standing
      subjects.
AB  - The main purpose of the present study has been to find an answer to the question:
      Can the subject generate anticipatory postural adjustments (APAs) when a
      predictable postural perturbation occurs in the absence of a voluntary action?
      Answering this question would allow us to distinguish between two competing
      hypotheses on the relation between APAs and voluntary movements. One hypothesis
      considers both APAsigma and voluntary "focal" movements different peripheral
      patterns associated with a single control process, while the alternative
      hypothesis considers them outcomes of two parallel control processes. Healthy
      subjects performed series of loading and unloading trials that included: (1)
      catching a falling load onto another load held in extended hands; (2) catching a
      falling load onto a tray attached to the trunk; (3) allowing a falling load to
      hit another load out of the extended hands, causing an unloading; and (4)
      releasing a load held in extended hands by a voluntary shoulder movement. In
      series 1, precautions were taken to avoid possible small hand movements prior to
      the impact of the falling load. Available visual information on the trajectory of
      the falling load was manipulated. In all conditions, except when the subject's
      eyes were closed, APAs were seen with patterns that were adequate for
      counteracting expected perturbations. Quantitative electromyographic indices of
      APAs depended on the availability of visual information and particular methods of
      introducing postural perturbations despite the fact that the magnitude of the
      perturbation was always the same. Our findings support a hypothesis that control
      processes resulting in APAs can be different from control processes associated
      with focal voluntary movements.

PMID- 11465745
TI  - Asymmetry of motor cortex excitability during a simple motor task: relationships
      with handedness and manual performance.
AB  - Transcranial magnetic stimulation (TMS) was used to assess the relative
      contribution of the corticospinal (CS) pathway in activating the first dorsal
      interosseous (FDI) muscle in each hand of 16 right- (RH) and 16 left-handed (LH)
      subjects with varied degrees of hand preference. It was hypothesised that
      asymmetry in corticospinal activation of the two hands may be related to hand
      preference and interlimb differences in manual performance. Subjects performed
      isometric index finger abduction at force levels of 0.5 N, 1 N and 2 N while TMS
      was applied at resting threshold intensity (T), 0.9T, or 0.8T. The amount of
      contraction-induced facilitation of the muscle evoked potential (MEP) was used as
      an estimate of corticospinal involvement in the task. Patterns of MEP
      facilitation in each hand were compared with measures of manual performance
      (finger tapping speed, Purdue pegboard, maximal FDI strength). Threshold TMS
      intensities for an MEP in FDI at rest were similar in LH and RH subjects, and did
      not vary between hands. Facilitation of the MEP with voluntary activation was
      larger overall on the left side (P<0.05), but the asymmetry was dependent on the
      degree of lateralisation of hand preference. For subjects with consistent hand
      preference (either LH or RH), MEP facilitation in active FDI was larger for the
      left hand. For non-consistent RH subjects, contraction-induced MEP facilitation
      was larger in the right FDI muscle than the left. Asymmetry of MEP facilitation
      was not correlated with differences between hands in finger tapping speed or
      performance in the pegboard task, but was associated with relative differences in
      FDI strength. MEP facilitation tended to be larger in the stronger FDI muscle of
      the pair. We conclude that corticospinal involvement in the command for index
      finger abduction is generally greater when the left hand is used, although in RH
      subjects the asymmetry is influenced by the degree of lateralisation of hand
      preference. The corticospinal asymmetry is not related to speed or dexterity of
      finger movements, but the association with muscle strength suggests that it may
      be influenced in part by preferential use of one hand for tasks which strengthen
      the FDI muscle.

PMID- 11465746
TI  - Impaired motor cortical inhibition in Parkinson's disease: motor unit responses
      to transcranial magnetic stimulation.
AB  - Transcranial magnetic stimulation (TMS)-induced corticospinal volleys can be
      investigated in detail by analysing the firing pattern modulation of active motor
      units (MUs) at close to threshold stimulation strengths. In amyotropic lateral
      sclerosis (ALS) these volleys are dispersed and prolonged, attributed to altered
      motor cortical excitability. Impaired intracortical inhibition, as found in ALS,
      is not unique to this disease, but is also a well-established finding in
      Parkinson's disease (PD). The present study explored whether reduced inhibition
      in the motor cortex in PD is accompanied by similar changes in motor unit firing
      modulation by TMS as are found in ALS. TMS was applied to the contralateral motor
      cortex during a low-force voluntary elbow flexion while 126-channel surface
      electromyography (SEMG) was recorded from the brachial biceps muscle. A recently
      developed method for SEMG decomposition was used to extract the firing pattern of
      up to five simultaneously active MUs. Sixteen MUs in 7 PD patients and 17 MUs in
      5 healthy control subjects were analysed and peristimulus time histograms (PSTHs)
      and interspike interval change functions (IICFs) were calculated. The IICF
      provides an estimate of the modulation of the postsynaptic membrane potential at
      the spinal motoneuron, evoked by the stimulus. In PD the duration of the PSTH
      peak was significantly increased and the synchrony was decreased. The excitatory
      phase at 20-50 ms of the IICF was broader in PD, reflecting a longer duration of
      the TMS-evoked excitatory postsynaptic potential. It is proposed that these
      results are due to prolonged corticospinal volleys resulting from impaired
      intracortical inhibition.

PMID- 11465747
TI  - Altered cortical activation with finger movement after peripheral denervation:
      comparison of active and passive tasks.
AB  - We wished to contrast cortical activation during hand movements in profoundly
      weak patients with motor neuropathy and in normal controls using a paradigm that
      is behaviourally matched between the two groups. Previous work has suggested that
      a passive movement task could be appropriate. Using functional magnetic resonance
      imaging (fMRI), we first characterised patterns of brain activation during active
      and passive index finger movements in healthy controls (n=10). Although the
      relative activation differences were highly variable, there was a trend for the
      mean number of significantly activated voxels in the primary motor cortex
      contralateral to the hand moved (CMC) to be lower for the passive than for the
      active task (40% relative decrease, P=0.09). There was a small posterior shift in
      the centre of mass of the CMC (mean, 8 mm, P<0.02) and of the ipsilateral
      sensorimotor cortex (IMC) (mean, 11 mm, P<0.05). No activation with passive
      movement was found in the patients with severe distal sensory neuropathy (n=2),
      suggesting that activation with passive movements is dependent on sensory
      feedback and unlikely to be due to mental imagery alone. In contrast, patients
      with severe pure motor neuropathies (MN, n=2) showed substantial increases in the
      volumes of activation compared to controls. The relative increases in numbers of
      voxels activated above threshold in different regions of interest for both the
      active (MN/controls: CMC, 2. 1; IMC, 8.1; supplementary motor area [SMA], 5.2)
      and passive (CMC, 2.6; IMC, 8.0; SMA, 5.1) tasks were similar. These results
      confirm expansion of cortical representation for finger movement in patients with
      motor neuropathy and demonstrate central reorganisation as a consequence of the
      motor nerve loss. An expanded representation for finger movement in the primary
      motor cortex with peripheral weakness suggests the possibility that the primary
      motor cortex may encode motor unit activation rather directly.

PMID- 11465748
TI  - Movement-related potentials in Huntington's disease: movement preparation and
      execution.
AB  - Movement-related potentials (MRPs) reflect increasing cortical activity related
      to the preparation and execution of voluntary movement. Execution and preparatory
      components may be separated by comparing MRPs recorded from actual and imagined
      movement. Imagined movement initiates preparatory processes, but not motor
      execution activity. MRPs are maximal over the supplementary motor area (SMA), an
      area of the cortex involved in the planning and preparation of movement. The SMA
      receives input from the basal ganglia, which are affected in Huntington's disease
      (HD), a hyperkinetic movement disorder. In order to further elucidate the effects
      of the disorder upon the cortical activity relating to movement, MRPs were
      recorded from ten HD patients, and ten age-matched controls, whilst they
      performed and imagined performing a sequential button-pressing task. HD patients
      produced MRPs of significantly reduced size both for performed and imagined
      movement. The component relating to movement execution was obtained by
      subtracting the MRP for imagined movement from the MRP for performed movement,
      and was found to be normal in HD. The movement preparation component was found by
      subtracting the MRP found for a control condition of watching the visual cues
      from the MRP for imagined movement. This preparation component in HD was reduced
      in early slope, peak amplitude, and post-peak slope. This study therefore
      reported abnormal MRPs in HD, particularly in terms of the components relating to
      movement preparation, and this finding may further explain the movement deficits
      reported in the disease.

PMID- 11465749
TI  - The phospholipase A2 inhibitor quinacrine prevents increased immunoreactivity to
      cytoplasmic phospholipase A2 (cPLA2) and hydroxynonenal (HNE) in neurons of the
      lateral septum following fimbria-fornix transection.
AB  - The distribution of cytoplasmic phospholipase A2 (cPLA2), 4-hydroxynonenal (HNE),
      and choline acetyltransferase (ChAT) was studied in the septum and hippocampus of
      rats at various time intervals after fimbria-fornix (FF) transection. Very little
      cPLA2 or HNE immunoreactivity was observed in the normal medial or lateral
      septum, whereas a large increase in immunoreactivity with both antibodies was
      observed in the lateral septum one week after transection. The increase in cPLA2
      or HNE staining in the lateral septum after FF transection was completely blocked
      by intraperitoneal injections (once daily) of a lipophilic inhibitor of
      phospholipase A2, quinacrine (5 mg/kg), showing the importance of phospholipase
      A2 in generation of arachidonic acid, which is a target for lipid peroxidation
      and formation of 4-hydroxynonenal. Quinacrine prevented not only a rise in HNE
      immunoreactivity, but also a rise in cPLA2 immunoreactivity, showing that cPLA2
      expression itself is depressed by the drug, in addition to its well-known effect
      on blocking the catalytic action of phospholipase A2. No increase in cPLA2 or HNE
      immunoreactivity was observed in neurons of the medial septum after fimbria
      fornix transection, even though these showed a decrease in ChAT staining after
      the lesion. This suggests that glutamate released from transected
      hippocamposeptal afferents or increased activity of the supramammillary area
      following FF transection may lead to increased cPLA2 and HNE immunreactivity,
      whereas retrograde degeneration in neurons may not. We conclude that there is
      free-radical damage, as evidenced by HNE formation in neurons of the lateral
      septum after fimbria-fornix transection, and that this increase in HNE is
      dependent on phospholipase A2 activity.

PMID- 11465750
TI  - Characterization of pretectal-nuclear-complex afferents to the pulvinar in the
      cat.
AB  - We investigated anatomical and physiological properties of the projection from
      the pretectal nuclear complex (PNC) to the ipsilateral lateral posterior-pulvinar
      complex in the cat. After Phaseolus vulgaris leucoagglutinin injections into the
      PNC, the majority (70%) of anterogradely labeled terminals was localized in the
      pulvinar proper, the remaining 30% were scattered in the lateral and medial
      portions of the LP. No PNC neuron retrogradely labeled from the pulvinar was
      found to also express glutamic acid decarboxylase (GAD) mRNA, although a large
      number of neurons carrying the GAD label were found in close vicinity. In
      contrast, 69% of retrogradely labeled PNC cells also displayed glutamate-like
      immunoreactivity. Twenty-six out of 96 (27%) visually responsive pulvinar neurons
      were orthodromically activated by electrical stimulation of the ipsilateral PNC
      at latencies between 1 and 10 ms (median 1.9 ms). All orthodromically activated
      neurons responded well to the onset and offset of large visual stimuli and to
      sudden stimulus shifts. Whenever a saccadic eye movement was executed, these
      neurons were also activated, except during saccades in darkness. The comparison
      of saccade-evoked response with responses to visual stimuli that elicit similar
      retinal image shifts revealed that pretectorecipient pulvinar neurons also seem
      to receive a saccade-related non-visual input. All response properties correspond
      to those of a specific class of pulvinar neurons that have been termed "SV"
      neurons because they respond to visual stimulation as well as during saccades.
      They also closely resemble response properties of PNC neurons that project to the
      ipsilateral pulvinar. The results support the proposal that PNC cells not only
      directly activate their postsynaptic target neurons in the pulvinar, but that
      they also provide a visual input to these neurons that greatly contributes to
      their response characteristics.

PMID- 11465751
TI  - Attentional processing of colour and location cues.
AB  - The aim of the present experiment was to investigate attentional processing of
      colour and location cues using a detection task. Subjects were required to
      respond to cued corners of a line drawing of a three-dimensional cube. Both cue
      and target were highlighted in red or green in one corner of the cube. Cues could
      be valid or invalid with respect to both the colour and location of subsequent
      targets. Results indicated a significant main effect of location validity, but no
      main effect of colour validity. Results also indicated that significant colour
      cueing effects were evident when location cues were invalid. These data also
      suggested different time courses for the processing of location and colour
      information. Location validity effects were largest at the shortest interstimulus
      interval (ISI) and decreased slightly with increasing ISI. In contrast, colour
      validity effects were absent at the shortest ISI, but thereafter increased with
      increasing ISI. The results of this experiment indicate that colour cues can be
      effective even in an inherently spatial task, provided there is sufficient time
      for the processing of colour information.

PMID- 11465752
TI  - Redistribution in I-123 N-isopropyl-p iodoamphetamine single-photon emission
      computed tomography in cerebrovascular disease and the effects of rehabilitation.
AB  - We performed N-isopropyl-p (I-123) iodoamphetamine (IMP) single-photon emission
      computed tomography (SPECT) on 28 patients with severe cerebrovascular disease
      before rehabilitation, and compared the degree of redistribution and the
      assessment of activities of daily living (ADL). We calculated a redistribution
      (RD) ratio in the central and peripheral parts of the lesions: RD ratio (c) and
      RD ratio (p). We classified the patients into four groups based on the degree of
      redistribution: complete: both RD ratio (c) and (p) > or = 75; peripheral: RD
      ratio (c) < 75, RD ratio (p) > or = 75; incomplete: both RD ratio (c) and (p) <
      75 and at least one of RD ratio (c) or (p) > or = 25; no redistribution: both RD
      ratio (c) and (p) < 25. We assessed the ADL using the modified Barthel index
      (BI). deltaBI was defined as BI after rehabilitation-BI before rehabilitation
      (BIpost-BIpre). The deltaBI of the four groups were as follows: complete
      redistribution group (40.8 +/- 22.8), peripheral-redistribution group (40.0 +/-
      15.8), incomplete-redistribution group (27.2 +/- 22.6), no-redistribution group
      (8.8 +/- 12.3). The deltaBI of the complete and peripheral redistribution groups
      were significantly higher than that of the no-redistribution group. However,
      deltaBI was almost the same in the complete- and peripheral-redistribution
      groups. This suggests that the effect of rehabilitation might be closely related
      to the viability of the peripheral part of the lesion.

PMID- 11465753
TI  - The value of diffusion-weighted imaging for prediction of lasting deficit in
      acute stroke: an analysis of 134 patients with acute neurologic deficits.
AB  - Acute stroke is one of the three major causes of death and disability in the
      United States. Now that new, and possibly effective therapy is becoming
      available, accurate, rapid diagnosis is important to provide timely treatment,
      while avoiding the risk of complications from unnecessary intervention. Our
      objective was to test the hypothesis that use of echo-planar (EPI) diffusion
      weighted imaging (DWI) is more accurate than conventional T2 weighted MRI in
      predicting progression to stroke in patients with acute ischemic neurologic
      deficits. We studied 134 patients presenting with acute neurologic deficits to a
      community hospital emergency room with both conventional MRI and DWI within 72 h
      of the onset of the acute deficit. We found DWI significantly more sensitive to
      permanent neurologic deficit at discharge (sensitivity 0.81) than conventional
      MRI (sensitivity 0.41). When available, DWI should be considered for routine use
      in patients being imaged for acute stroke.

PMID- 11465754
TI  - Diffusion-weighted imaging of the brain: comparison of stimulated- and spin-echo
      echo-planar sequences.
AB  - We used a rat model of focal cerebral ischaemia to compare stimulated-echo (STE)
      and spin-echo (SE) echo planar (EPI) diffusion-weighted sequences as regards
      image quality and accuracy of calculation of apparent diffusion coefficients
      (ADC). Focal cerebral ischaemia was induced by endovascular occlusion of the
      middle cerebral artery in five rats. MRI was performed on a 2.35 tesla imager.
      For diffusion-weighted imaging (DWI) we used STE-EPI and SE-EPI with different
      diffusion times (delta) of 15, 30, 45, 60, 75 and 90 ms using values of b of 200,
      300, 400, 500, 600 and 700 s/mm2. We assessed image quality, the signal-to-noise
      ratio (SNR) and the accuracy of the ADC calculated from both sequences. Infarcts
      were delineated in all cases, independent of sequence type and delta. The image
      quality and SNR of the SE-EPI images were significantly better, with a higher SNR
      than STE-EPI images for short and intermediate values of delta. However, when
      delta reached 75 ms STE-EPI became superior to SE-EPI. ADC calculated from STE
      EPI images were smaller than those from SE-EPI images for short and intermediate
      diffusion times, possibly because of the lower SNR of the former. We suggest that
      SE-EPI sequences be used for DWI of the brain, particularly on experimental
      systems and whole-body imagers with enhanced gradient hardware, where it is
      possible to run highly diffusion-weighted sequences (b > 500 s/mm2) with delta
      less than 50 ms. However, when using very long values of delta because of
      hardware restrictions or for measurement of restricted diffusion, STE sequences
      give better results.

PMID- 11465755
TI  - Multivariate analysis of regional metabolic differences in normal ageing on
      localised quantitative proton MR spectroscopy.
AB  - We performed multivariate analysis of regional differences and normal age-related
      changes in metabolites in the lentiform nucleus and frontal lobe, as measured by
      proton MRS. The cerebrospinal fluid (CSF) in the measurement area was estimated
      and the metabolite concentration adjusted. The concentration of N-acetylaspartate
      (NAA) in the lentiform nucleus decreased with ageing (F = 4.11, P < 0.01), but
      that in the frontal lobe did not change (F = 0.93, P = 0.45). This is in marked
      contrast with pathological dementia, such as Alzheimer's disease. In this
      multivariate analysis, the normal change in metabolism with ageing differed
      depending on the cerebral region, suggesting that metabolite concentrations,
      especially that of NAA may be useful metabolic indices for discriminate normal
      ageing from pathological dementia.

PMID- 11465756
TI  - Spontaneous intracranial hypotension: the value of brain measurements in
      diagnosis by MRI.
AB  - Caudal brain displacement is inconstantly reported as an MRI feature of
      spontaneous intracranial hypotension (SIH). We reviewed the clinical data and MRI
      of eight patients diagnosed as having SIH and investigated the possibility of
      more precise assessment. On midsagittal images we measured four anatomical
      landmarks: the position of the cerebellar tonsils, fourth ventricle, and
      infundibular recess, plus the angle between the bicommissural line and a line
      tangential to the floor of the fourth ventricle; midsagittal images from 89
      normal controls were also measured. On statistical analysis, all measurements
      differed in the two groups, and the difference was significant for the cerebellar
      tonsils, fourth ventricle, and infundibular recess. Some overlap between patients
      and controls was found for each measurement; however, all the patients had two
      (two patients) or more (six) values outside the range in normal controls range or
      not above their 1st quartile. Measurement of the position of the third ventricle
      seemed particularly sensitive. We suggest that examination of midsagittal images
      can help in diagnosing clinically suspected SIH.

PMID- 11465757
TI  - Dural congestion accompanying meningioma invasion into vessels: the dural tail
      sign.
AB  - Our purpose was to verify the histological appearance of the dural tail
      accompanying meningiomas on MRI. We studied seven patients such a dural tale. We
      examined the point of attachment of the tumour and the adjacent dura mater
      histologically. In all patients, rich vascularity and dilated vessels were
      observed in the dura mater at the point of attachment of the tumour; tumour cells
      invaded the dura mater and vessels, packing the latter. In the adjacent dura
      mater, showing as a dural tail on MRI, there was tumour-cell invasion in only one
      patient. Vascular congestion around the vessels compacted by the tumour cells in
      the dura mater and dilated vessels were seen in all patients. We therefore
      suggest that the mechanism of the dural tail sign is as follows. First, tumour
      cells invade vessels and pack them at the point of tumour attachment. Then,
      vessel congestion is induced in the adjacent dura mater, as a result of which it
      enhances markedly, giving rise to the dural tail sign.

PMID- 11465758
TI  - The value of intraoperative angiography in surgery of intracranial aneurysms: a
      prospective study in 126 patients.
AB  - The value of intraoperative digital subtraction angiography in surgery for
      intracranial aneurysms, the benefits and cost-effectiveness are a matter of
      discussion. We prospectively studied 126 patients with 144 aneurysms, most on the
      anterior intracranial circulation, who underwent clipping and intraoperative
      angiography. Follow-up was 28.4 +/- 13.1 months. We tried to work out the
      indications for intraoperative angiography of the anterior circulation and its
      cost-effectiveness. In 10.3 % of patients (9 % per aneurysm) unexpected findings
      were shown by intraoperative angiography: inadequately clipped aneurysms in 10
      (7.9 %), a completely unclipped aneurysm in one (0.8 %) and occluded major
      arteries in two (1.6 %). A broad neck was a variable of statistical significance
      for inadequate clipping or stenosis or occlusion of an adjacent vessel. There was
      a strong trend for aneurysms more than 15 mm in diameter to be "risky". Their
      site was not a predictive factor. We believe that intraoperative angiography is
      indicated in surgery not only on large and giant aneurysms, but also broad-based
      aneurysms of the anterior cerebral circulation regardless of their size. It is
      cost-effective compared to postoperative angiography. The rate of stroke in our
      hands was 0.8%.

PMID- 11465759
TI  - Stress reduction through music in patients undergoing cerebral angiography.
AB  - We studied the influence of music on stress reaction of patients during cerebral
      angiography. We randomised 30 patients to a music or a control group. We measured
      stress hormones, blood pressure, heart rate and psychological parameters.
      Patients examined without music showed rising levels of cortisol in plasma,
      indicating high stress levels, while cortisol in patients examined with music
      remained stable. Systolic blood pressure was significantly lower listening to
      music. Patients with a high level of fear did appear to benefit particularly from
      the music.

PMID- 11465760
TI  - Duplication of the vertebral artery: report of two cases and review of the
      literature.
AB  - Duplication of the vertebral artery is rare. We report two cases in which it was
      an incidental finding. In the first, duplication of the right vertebral artery
      was demonstrated by magnetic resonance angiography (MRA) and conventional
      angiography. The second patient had duplication of the right vertebral artery
      demonstrated by MRA. We discuss the origin of this abnormality, its radiological
      implications and its potential clinical significance are discussed.

PMID- 11465761
TI  - Treatment planning in severe scoliosis: the role of MRI.
AB  - The use of magnetic resonance imaging (MRI) in the preoperative investigation of
      children with idiopathic scoliosis is controversial. Syringomyelia and other
      intraspinal lesions may be risk factors for neurological injury during surgical
      correction. Our purpose was to investigate whether pathology of the neuraxis is
      associated with scoliosis and to detect lesions which may threaten neurological
      sequelae during distraction and instrumented correction. We obtained T1- and T2
      weighted images of 40 children (28 girls, 12 boys), mean age 12.7 years with
      severe idiopathic scoliosis (Cobb angle 50-70 degrees) obtained in coronal,
      sagittal and axial planes from the posterior cranial fossa to the sacrum, and
      these were assessed by two neuroradiologists and an orthopaedic surgeon prior to
      further treatment planning. Abnormalities of the neuraxis were found in 24
      patients (60%); five (12%) had two or more lesions. No abnormalities of the
      neuraxis were found in 16 patients (40%). There were 15 patients (38%) with
      intraspinal abnormalities who deteriorated clinically and nine (22%) who showed
      no clinical changes. We transferred 16 patients (40%) from the orthopaedic to the
      neurosurgical department for further assessment. Our results suggest that one
      should investigate the neuraxis with MRI before contemplating orthopaedic
      surgical correction of severe idiopathic scoliosis, because the findings may lead
      to a change of procedure.

PMID- 11465762
TI  - MRI in Lyme disease of the spinal cord.
AB  - We report a case of Lyme myelitis in a 31-year-old man, presenting with a conus
      medullaris syndrome. MRI demonstrated contrast enhancement on the pial surface of
      the lower thoracic cord and conus medullaris. Elevated blood immunoglobulins and
      IgM antibodies against Borrelia burgdorferi in the cerebrospinal fluid (CSF) were
      found. Leptomeningitis may be the first stage of spinal infection in Lyme
      disease, preceding parenchymal infection leading to myelitis. Vasculitis is
      probably the major mechanism. MRI findings are nonspecific and the diagnosis is
      given by serum and CSF analyses. Early treatment with antibiotics and high doses
      steroids may result in complete recovery, as in this case.

PMID- 11465763
TI  - Myxopapillary ependymoma of the conus medullaris with subarachnoid haemorrhage:
      MRI in two cases.
AB  - Subarachnoid haemorrhage due to cauda equina tumour is rare. We report two
      myxopapillary ependymomas of the conus terminalis, presenting with in this way.
      Rims of low signal were observed at their upper and lower borders, mainly on T2
      weighted images. This finding has been described in ependymomas of the cervical
      region but not, to our knowledge, in myxopapillary ependymomas of the conus
      terminalis.

PMID- 11465764
TI  - MRI of perineural extramedullary granulocytic sarcoma.
AB  - Granulocytic sarcoma is an extramedullary solid tumour consisting of myelogenous
      leukaemic blast cells, usually seen in acute myeloid leukaemia and less commonly
      in patients with chronic myeloid leukaemia or myeloproliferative disorders. Blast
      cells have a predilection for periosteal and perineural regions and rarely
      precede evidence of systemic disease. We present two patients, aleukaemic on
      peripheral blood counts, both at presentation and during subsequent treatment. We
      present the MRI features of this rare but important condition.

PMID- 11465765
TI  - Regional magnetic resonance spectroscopy of the brain in autistic individuals.
AB  - We studied the variations in the concentration of metabolites with brain region
      and age in autistic individuals and normal controls using multiple analysis of
      covariance. We examined 55 autistic individuals (2-21 years old, 47 male and
      eight female) and 51 normal children (3 months-15 years old, 26 boys and 25
      girls). Single volumes of interest were placed in the frontal, parietal and
      temporal region on both sides, the brain stem and cingulate gyrus. The
      concentration of each metabolite was quantified by the water reference method.
      The concentration of N-acetylaspartate in the temporal regions (Brodmann's areas
      41 and 42) in the autistic individuals were significantly lower than those in the
      controls (P < 0.05), but concentrations in other regions were not significantly
      different between the autistic individuals and controls. This suggests low
      density or dysfunction of neurones in Brodmann's areas 41 and 42 in autistic
      individual, which might be related to the disturbances of the sensory speech
      centre (Wernicke's area) in autism.

PMID- 11465766
TI  - Treatment of a cavernous sinus dural arteriovenous fistula by deep orbital
      puncture of the superior ophthalmic vein.
AB  - In a patient with progressive ophthalmological problems, including uncontrolled
      intraocular pressure related to a cavernous sinus dural arteriovenous fistula,
      urgent intervention may be necessary to prevent permanent visual loss. We report
      a case in which inadequate transarterial embolisation and lack of access for
      transvenous catheterisation, including a direct approach through the superior
      ophthalmic vein, preceded percutaneous puncture of the superior ophthalmic vein
      deep within the orbit, permitting venous occlusion without complications. This
      case demonstrates that deep orbital puncture of the vein is feasible for
      occlusion of a cavernous sinus dural arteriovenous fistula.

PMID- 11465767
TI  - Choroid plexus papilloma of the third ventricle: angiography, preoperative
      embolization, and histology.
AB  - We report a unique case of choroid plexus papilloma of the third ventricle in an
      8-month-old girl in which preoperative embolization played a salient role in
      management. Initial surgery was aborted due to excessive bleeding. Cerebral
      angiography demonstrated enlarged posterior choroidal arteries feeding the tumor,
      and intense, persistent tumor staining. These vessels were effectively embolized
      to stasis with polyvinyl alcohol particles. The patient underwent a second
      craniotomy and complete resection of the tumor with minimal blood loss.
      Postsurgical histology showed postembolization iatrogenic intratumoral necrosis.

PMID- 11465768
TI  - MRI detection of unsuspected vertebral injury in acute spinal trauma: incidence
      and significance.
AB  - OBJECTIVE: Multilevel spinal injury is well recognised. Previous studies
      reviewing the radiographs of spinal injury patients have shown an incidence of
      15.2% of unsuspected spinal injury. It is recognised that magnetic resonance
      imaging (MRI) can identify injuries that are not demonstrated on radiographs. The
      objective of this study was to determine the incidence and significance of spinal
      injuries using MRI in comparison with radiographs. DESIGN AND PATIENTS: The
      radiographs and MR images of 110 acute spinal injury patients were reviewed
      independently of each other and the findings were then correlated to determine
      any unsuspected injury. RESULTS: MRI detected vertebral body bone bruises
      (microtrabecular bone injury) in 41.8% of spinal injury patients which were not
      seen on radiographs. These bone bruises were best appreciated on sagittal short
      tau inversion recovery MR sequences and seen at contiguous and non-contiguous
      levels in relation to the primary injury. CONCLUSION: This level of incidence of
      bone bruises has not previously been appreciated. We recommend that patients
      undergoing MRI for an injured segment of the spine are better assessed by MRI of
      the entire spine at the same time to exclude further injury.

PMID- 11465769
TI  - Evaluation of grades 3 and 4 chondromalacia of the knee using T2*-weighted 3D
      gradient-echo articular cartilage imaging.
AB  - OBJECTIVE: To determine the accuracy of T2*-weighted three-dimensional (3D)
      gradient-echo articular cartilage imaging in the identification of grades 3 and 4
      chondromalacia of the knee. DESIGN AND PATIENTS: A retrospective evaluation of 80
      patients who underwent both arthroscopic and MRI evaluation was performed. The 3D
      images were interpreted by one observer without knowledge of the surgical
      results. The medial and lateral femoral condyles, the medial and lateral tibial
      plateau, the patellar cartilage and trochlear groove were evaluated. MR cartilage
      images were considered positive if focal reduction of cartilage thickness was
      present (grade 3 chondromalacia) or if complete loss of cartilage was present
      (grade 4 chondromalacia). Comparison of the 3D MR results with the arthroscopic
      findings was performed. RESULTS: Eighty patients were included in the study
      group. A total of 480 articular cartilage sites were evaluated with MRI and
      arthroscopy. Results of MR identification of grades 3 and 4 chondromalacia, all
      sites combined, were: sensitivity 83%, specificity 97%, false negative rate 17%,
      false positive rate 3%, positive predictive value 87%, negative predictive value
      95%, overall accuracy 93%. CONCLUSION: The results demonstrate that T2*-weighted
      3D gradient-echo articular cartilage imaging can identify grades 3 and 4
      chondromalacia of the knee.

PMID- 11465770
TI  - Mucoid degeneration of the anterior cruciate ligament mistaken for ligamentous
      tears.
AB  - OBJECTIVE: To describe the MR features of mucoid degeneration of the anterior
      cruciate ligament (ACL) in a series of patients with MRI findings that were
      mistaken for tears in the majority of cases but who were found to have an intact
      ligament at arthroscopy. We will suggest a pathologic entity corresponding to
      this finding and describe some characteristic features that can be used to
      identify this entity on MRI. DESIGN: A retrospective analysis of 10 MRI
      examinations of the knee was performed after arthroscopic evaluation.
      Prearthroscopic MRI findings had been interpreted as a tear in six patients
      prospectively and in the remaining four the diagnosis of mucoid degeneration was
      suggested and ultimately proven. All patients had an intact ACL by preoperative
      clinical examination, examination under anesthesia, and at arthroscopy. RESULTS:
      MRI examinations demonstrated an ill-defined ACL, greater in girth than the
      normal ligament and characterized by increased signal on all sequences. The high
      signal ligament was oriented in the normal direction of the ACL. The overall
      appearance of the ligament was retrospectively described as like a celery stalk.
      Arthroscopy demonstrated mechanically intact ligaments with a normal to expanded
      external appearance. Probing of three of the ligaments caused a material to be
      expressed and pathologic evaluation resulted in the diagnosis of cystic, mucoid
      degeneration. CONCLUSION: Mucoid degeneration and an intact ACL can be suspected
      when an apparently thickened and ill-defined ligament with increased signal
      intensity on all sequences is identified in a patient with a clinically intact
      ligament.

PMID- 11465771
TI  - Discoid lateral meniscus and the frequency of meniscal tears.
AB  - OBJECTIVE: To use MRI to determine the incidence of discoid lateral menisci in a
      large study population, and to compare those patients with those without a
      discoid meniscus in order to assess the impact of a discoid lateral meniscus on
      the frequency of meniscal tears. DESIGN AND PATIENTS: Results of 1,250 knee MRI
      studies were retrospectively reviewed. Using the criterion of three or more
      meniscal body segments on sequential sagittal images, 56 patients were found to
      have a discoid lateral meniscus. After exclusion of patients with prior knee
      surgery, 49 patients with a discoid lateral meniscus were compared with 1,146
      patients without a discoid meniscus. Patients were categorized as having tears of
      the medial meniscus, lateral meniscus, or both menisci. RESULTS: In our study
      population, there was a 4.5% incidence of discoid lateral meniscus. Seventy-one
      percent of patients with a discoid lateral meniscus had one or more meniscal
      tears, compared with 54% of the comparison group (P=0.01). The frequency of
      solitary lateral meniscal tears in the discoid group was also higher than in the
      comparison group: 20%.versus 11% (P=0.03). The frequency of solitary medial
      meniscal tears and concomitant tears of both menisci were not significantly
      different between the two groups. CONCLUSIONS: The discoid lateral meniscus is an
      uncommon variant, but not as rare as once believed. Compared with the normal
      semilunar meniscus, the discoid lateral meniscus has a higher frequency of
      meniscal tears, and solitary tears of the lateral meniscus are more common in the
      discoid variant. The frequency of medial meniscal tears is not altered by the
      presence of a discoid lateral meniscus.

PMID- 11465772
TI  - The diagnostic value of MRI scans for the diagnosis of chronic exertional
      compartment syndrome of the lower leg.
AB  - OBJECTIVE: A prospective descriptive study to determine the value of magnetic
      resonance imaging (MRI) as an aid in diagnosing (chronic) exertional compartment
      syndrome. DESIGN AND PATIENTS: MRI was performed in 21 patients (41 anterior
      compartments) with chronic compartment syndrome at rest and following physical
      exercise. Median (T2-weighted) signal intensity on the MRI scan was determined in
      the anterior and the (superficial) posterior compartment of the lower leg before
      and after exercise. Postexercise increases in the signal intensity in these two
      compartments were compared. After fasciotomy, a second MRI scan was performed in
      13 patients (25 anterior compartments) on the basis of the same protocol. MR
      studies were performed in 12 normal controls (24 anterior muscle compartments) on
      the basis of the same protocol. RESULTS: T2-weighted signal intensity increased
      by 27.5% (range 13.6-38.6%) following exercise in the anterior compartment of
      patients with a chronic compartment syndrome. In the posterior compartment this
      increase amounted to 4.25% (range 0-10.2%). Following fasciotomy, the increase in
      the anterior compartment was 4.1% (range 1.0-5.2%), while the increase in the
      posterior compartment amounted to 5.6% (range 0-11.0%), In normal controls, the
      increase in the anterior compartment was 7.6% (range 0-9. 1%), while in the
      posterior compartment it was 4.0% (range 0-7.2%). CONCLUSIONS: In patients with a
      chronic compartment syndrome, the affected (anterior) compartment shows a
      statistically significant increase in (T2-weighted) signal intensity during
      exercise compared with both the (superficial) posterior compartment and the
      anterior compartment of normal controls. This effect disappeared after
      fasciotomy. In view of the substantial increase in T2-weighted signal intensity,
      MRI can be used in diagnosing chronic compartment syndrome.

PMID- 11465773
TI  - Utility of MR arthrography in the diagnosis of adhesive capsulitis.
AB  - OBJECTIVE: Arthrographically, adhesive capsulitis is characterized by decreased
      joint volume; histologically, the capsule and synovium are thickened. We
      therefore compared using MR arthrography the joint volumes and capsule/synovial
      thickness of patients with and without adhesive capsulitis in order to assess the
      utility of MR arthrography in diagnosing adhesive capsulitis. DESIGN AND
      PATIENTS: The 1.5 T MR arthrography images of 28 subjects with (n=9) and without
      (n=19) adhesive capsulitis were compared. Adhesive capsulitis was diagnosed when
      there was an injected glenohumeral joint volume of less than 10 ml. Two masked
      observers working in consensus assessed the images for the relative amount of
      fluid in the biceps tendon sheath and axillary recess, corrugation at the margin
      of the capsule, capsule/synovial thickness, abnormalities of the rotator interval
      capsule, and for the presence of a cuff tear. RESULTS: There was a trend towards
      differences in capsular and synovial thickness (P>0.07) between the subjects with
      and without adhesive capsulitis; however, the controls had thicker
      synovium/capsules. Surprisingly, the amount of fluid in the axillary recess and
      biceps tendon sheath was not significantly different between the groups (P>0.25).
      There were more tears of the rotator cuff in controls than in patients with
      adhesive capsulitis (6, 3 vs 1, 1: complete, partial). Also, both corrugation (7
      vs 0) and interval abnormalities (7 vs 0) were more common in the controls.
      CONCLUSION: There appear to be no useful MR arthrographic signs of adhesive
      capsulitis. Capsular/synovial thickness, static fluid volume, and the presence of
      corrugation are inconclusive as MR arthrographic signs for distinguishing
      shoulders with adhesive capsulitis from those without.

PMID- 11465774
TI  - Malignancy in chronic ulcers and scars of the leg (Marjolin's ulcer): a study of
      21 patients.
AB  - OBJECTIVE: To study the imaging features of patients with chronic ulcers of the
      leg that were associated with malignancy. DESIGN AND PATIENTS: All patients who
      on biopsy were proven to have malignancy--the majority of which were squamous
      cell carcinoma-were included in a prospective study. Ulcers limited to the foot
      were excluded but ulcers of the leg which extended into the foot were included.
      Amputation was performed in all but two patients, due to pain, bleeding or tissue
      necrosis. RESULTS: The etiology was multifactorial. The mean duration of the
      ulcers was 36 years including venous ulcers, extensive scarring of the leg
      secondary to infection, injury or burns. One ulcer was secondary to a snake bite.
      The remainder, usually in the upper part of the leg, had repeated episodes of
      blunt trauma or knife wounds, which were also complicated by infections which
      failed to heal or, if they healed, regularly recurred. Although arterial
      insufficiency was not primary in any patient, most were of advanced age and it
      may have been an element in some patients. Despite infection, osteomyelitis was
      present in only one patient. The essential features were bone destruction, soft
      tissue mass and periosteal reaction. The bone destruction was visible on the
      radiographs in all but one case. The soft tissue masses varied in size but in
      general were very large. The periosteal reaction varied in type but most commonly
      was lamellated. The classic undulating solid periosteal reaction of venous stasis
      was only occasionally present. The periosteal reaction was nonspecific in the
      majority of cases and did not aid in the diagnosis or etiology. MRI and CT
      studies were performed in six patients. These were helpful in defining the extent
      of bone destruction and periosteal reaction but were not essential in management.
      CONCLUSION: Chronic ulcer present for decades that then undergoes malignant
      change is a disease of developing countries where patients only consult
      physicians when they have developed complications such as pain, bleeding or
      tissue necrosis. Chronic ulcers may require to be biopsied at regular intervals
      as malignant change in these ulcers is directly related to their duration.

PMID- 11465775
TI  - Dural ectasia and conventional radiography in the Marfan lumbosacral spine.
AB  - OBJECTIVE: To determine how well conventional radiographic findings can predict
      the presence of dural ectasia in Marfan patients. DESIGN AND PATIENTS: Twelve
      Marfan patients without dural ectasia and 21 Marfan patients with dural ectasia
      were included in the study. Five radiographic measurements were made of the
      lumbosacral spine: interpediculate distance, scalloping value, sagittal canal
      diameter, vertebral body width, and transverse process width. RESULTS: The
      following measurements were significantly larger in patients with dural ectasia:
      interpediculate distances at L3-L4 levels (P<0.03); scalloping values at the L1
      and L5 levels (P<0.05); sagittal diameters of the vertebral canal at L5-S1
      (P<0.03); transverse process to width ratios at L2 (P<0.03). Criteria were
      developed for diagnosis of dural ectasia in Marfan patients. These included
      presence of one of the following: interpediculate distance at L4 > or = 38.0 mm,
      sagittal diameter at S1 > or = 18.0 mm, or scalloping value at L5 > or = 5.5 mm.
      CONCLUSION: Dural ectasia in Marfan syndrome is commonly associated with several
      osseous changes that are observable on conventional radiographs of the
      lumbosacral spine. Conventional radiography can detect dural ectasia in patients
      with Marfan syndrome with a very high specificity (91.7%) but a low sensitivity
      (57.1%).

PMID- 11465776
TI  - Symmetrical enchondromatosis without vertebral involvement and with cone-shaped
      phalangeal epiphyses.
AB  - A new type of enchondromatosis is described with a symmetrical distribution but
      not involving the spine and characterised by severe ankle deformity, shortening
      of metacarpals and phalanges, and cone-shaped phalangeal epiphyses.

PMID- 11465777
TI  - Cellular schwannoma: a benign neoplasm sometimes overdiagnosed as sarcoma.
AB  - A case of cellular schwannoma originating in the left lumbar paraspinal region is
      described. The diagnosis was originally made on needle biopsy material. The
      histological examination is usually not sufficient to correctly diagnose this
      benign neoplasm. Bone erosion, neurological symptoms, caused by compression of
      the spinal roots, together with hypercellularity, pleomorphism and an occasional
      increase in mitotic activity, may lead to an erroneous diagnosis of malignancy.
      Immunohistochemistry and ultrastructural analysis are helpful in confirming the
      diagnosis. The recognition of this entity avoids unnecessary overtreatment of
      these patients.

PMID- 11465778
TI  - Anterior approach for knee arthrography.
AB  - OBJECTIVE: To develop a new method of magnetic resonance arthrography (MRA) of
      the knee using an anterior approach analogous to the portals used for knee
      arthroscopy. DESIGN: An anterior approach to the knee joint was devised mimicking
      anterior portals used for knee arthroscopy. Seven patients scheduled for routine
      knee MRA were placed in a decubitus position and under fluoroscopic guidance a
      needle was advanced from a position adjacent to the patellar tendon into the knee
      joint. After confirmation of the needle tip location, a dilute gadolinium
      solution was injected. RESULTS AND CONCLUSION: All the arthrograms were
      technically successful. The anterior approach to knee MRA has greater technical
      ease than the traditional approach with little patient discomfort.

PMID- 11465779
TI  - Differential diagnosis of Stickler syndrome.

PMID- 11465780
TI  - Links between social class and common mental disorders in Northeast Brazil.
AB  - BACKGROUND: Social class is an important aspect of all societies. Social class
      differences in the prevalence of common mental disorder are likely to vary
      according to time, culture and stage of economic development. The present study
      aimed to investigate the intermediaries between social class and common mental
      disorder in a deprived area of Northeast Brazil. The Self Reporting Questionnaire
      (SRQ) was used to estimate the prevalence of common mental disorder. METHOD: A
      cross-sectional survey was conducted of 683 adults, aged 15 years and over,
      living in a random sample of private households in area II of Olinda, Recife
      Metropolitan Region, Pernambuco, Brazil. RESULTS: Poor education (odds ratio, OR
      2.5, 95% CI 1.2-5.2; <5 years vs > or =11 years education) and low income (OR
      2.4, 95% CI 1.0-5.6; < or =1/4 minimum wage vs >1 minimum wage) were
      independently associated with the prevalence of common mental disorder.
      Univariate associations with occupation, housing conditions and possession of
      household appliances could be understood in part by their association with poor
      education. CONCLUSIONS: Brazil has the second most unequal distribution of income
      in the world. Disparity in educational attainment could be one of the most
      important factors perpetuating social inequalities in psychiatric disorder in the
      country.

PMID- 11465781
TI  - Psychological impact of the hurricane Mitch in Nicaragua in a one-year
      perspective.
AB  - BACKGROUND: Whereas natural disasters more commonly occur in low-income
      countries, almost all studies on psychological consequences have been conducted
      in the Western world. In countries where resources are poor it is of importance
      to know which groups should be targeted for early intervention after a disaster.
      The study aims at assessing the prevalence of post-traumatic stress disorder PTSD
      and of post-traumatic symptoms among people afflicted by hurricane Mitch in
      Nicaragua and at identifying risk factors for PTSD symptoms 6 months following a
      disaster. METHOD: At four primary health care centres, 496 consecutive adult
      patients were interviewed 6 months after hurricane Mitch regarding PTSD symptoms
      (Harvard Trauma Questionnaire, HTQ), disaster experiences and post-disaster help
      seeking. RESULTS: All individuals resident in the area during Mitch were judged
      to have experienced a trauma fulfilling A criteria for PTSD. Regarding more
      specific traumas, 39% reported a close relative to be dead or seriously injured
      and 72% had their house partly or completely destroyed. Prevalence of PTSD ranged
      from 9.0% in the worst afflicted area to 4.5% in a less damaged area. From a
      dimensional perspective, PTSD symptoms according to HTQ 6 months after the
      disaster were significantly associated with the death of a relative (beta
      coefficient 0.257, P = 0.000), a house destroyed (beta-coefficient 0.148, P =
      0.001), female sex (beta-coefficient 0.139, P = 0.001), previous mental health
      problems (beta-coefficient 0.109, P = 0.009) and illiteracy (beta-coefficient
      0.110, P = 0.009). Those with previous mental health problems (OR = 4.84; 95% CI
      = 3.04-7.66) were more likely than others to seek from help, any source whereas
      the opposite was true for illiterate people (OR = 0.38; 95% CI = 0.21-0.69). Of
      all respondents, 8.5% reported that they had thought of taking their lives, and
      illiterates (OR 2.84; 95% CI = 1.12-4.37) and those with previous mental health
      problems (OR 2.84; 95% CI = 1.12-4.57) were at particular risk for suicidal
      problems. One year after Mitch, half of those identified as PTSD cases at 6
      months still fulfilled the criteria for a PTSD diagnosis. CONCLUSION: PTSD
      represents a serious mental health problem after a disaster. Those with
      illiteracy, females and those with previous mental health problems should be
      targets for early post-disaster intervention.

PMID- 11465782
TI  - Social support and life events as risk factors for depression amongst women in an
      urban setting in Zimbabwe.
AB  - BACKGROUND: This paper explores the applicability of a psychosocial model of
      depression in an African setting. METHOD: Of a random sample of women (n = 172)
      from a Zimbabwean township, 79 had a severe life event in the year before
      interview. Twenty-nine who had an onset of depression were compared with 50 who
      did not. RESULTS: Having crisis support following a severe life event reduced the
      risk of onset of depression. The effect of crisis support was confounded by the
      number of severe events in the study year, but just persisted following
      adjustment for number of severe events and for socio-demographic factors. Women
      received crisis support more often from relatives than from partners or friends.
      The following variables were independently associated with onset of depression
      following a severe life event: number of life events in the previous 6 months,
      age, being in formal employment, having crisis support and separation from mother
      in childhood. CONCLUSION: This study supports the ubiquity of the social support
      construct. For Zimbabwe, the data suggest that crisis support from family members
      may be of particular importance in protecting against onset of depression.

PMID- 11465783
TI  - Epidemiology of suicide in Israel: a nationwide population study.
AB  - BACKGROUND: In Israel, some population characteristics and lifestyle patterns
      make epidemiological research on suicide of particular interest. The Israeli
      population is characterized by ethnic diversity, with a multi-religious, multi
      national mosaic of Jews and Arabs. These subgroups also vary in their suicidal
      behavior. The aims of the present study were to examine the trends in suicide
      incidence rates in Israel from 1984 to 1994, to identify sub-populations at high
      risk for suicide and to identify suicide methods associated with increased risk.
      METHODS: Suicide rate trends in Israel over the period from 1984 to 1994 were
      examined for four subgroups: Jewish men and women, and Arab men and women. Cases
      of undetermined external cause (UEC) of death were also considered. Mortality
      data were obtained from the computerized data files of the Israeli Central Bureau
      of Statistics, which includes cause of death and sociodemographic variables.
      Suicide was classified according to the ICD-9 codes. RESULTS: Suicide rates were
      higher for Jews than for Arabs, and higher for men than for women. The rates
      among both population and sex groups increased directly with age. A significant
      increase over the years studied was found for Jewish men, particularly in the 18-
      to 21-year-old age group. An increase in the use of firearms was noted, mainly in
      the groups in which total suicide rates increased. CONCLUSIONS: The findings of
      this study highlight the need for further studies to identify both sub
      populations at high risk for suicide, and societal trends such as lifestyles,
      immigration, military service, and media exposure to violence, as first steps
      toward planning of intervention programs to reduce suicide rates.

PMID- 11465784
TI  - The psychological well-being of family members of individuals with schizophrenia.
AB  - BACKGROUND: The purpose of the study was to attempt to understand the experience
      of family members of individuals with schizophrenia. More specifically, we wanted
      to determine whether a measure of caregiving would be a stronger predictor of the
      psychological well-being of families who have a member with schizophrenia than a
      measure of burden. METHOD: Forty-one family members of 30 individuals with
      schizophrenia were recruited. A measure of burden, a measure of the experience of
      caregiving, and the duration of the illness were used to determine the best
      predictor of psychological wellbeing. RESULTS: Regression analyses indicated that
      the strongest predictor of psychological well-being was the negative scale of the
      Experience of Caregiving Inventory (ECI). There was also a significant
      relationship between poor psychological well-being and short duration of illness.
      CONCLUSIONS: The findings of the study indicated that family members are
      significantly distressed as a result of having a family member with
      schizophrenia. There is support for using newer scales, like the ECI.
      Furthermore, increased family support is required in the early stages of the
      illness.

PMID- 11465785
TI  - Beliefs about causation of schizophrenia: do Indian families believe in
      supernatural causes?
AB  - BACKGROUND: Beliefs about the causation of schizophrenia could influence the
      attitudes patients' families adopt towards the patient and may also influence
      their help-seeking behaviour. Indian families have been typically described as
      often believing in causes like supernatural forces and therefore seeking help
      from magico-religious healers. In the changing mental health scenario in India,
      this impression needs verification. METHOD: Key relatives living with 254 chronic
      schizophrenia patients were interviewed and asked to name the causes they
      believed were behind the illness. A list of possible causes was provided for the
      families to select from, and relatives were also encouraged to mention other
      possible causes, not featured in the list. The possible causes identified and the
      factors related to attributions made were analysed. RESULTS: A supernatural cause
      was named by only 12% of the families and as the only cause by 5%. Psychosocial
      stress was most commonly cited cause, followed by personality defect and
      heredity. A small number of families (14%) could not name any cause and 39% named
      more than one cause. Patient gender and education, duration of illness and the
      key relative's education and the nature of relationship were related to the type
      of causal attributions made. CONCLUSION: Families living with patients suffering
      chronic schizophrenia receiving treatment in urban India rarely subscribe to the
      idea of supernatural causation of the illness. The causal attributions made by
      them are fairly rational and understandable, given the relative lack of exposure
      to proper information about the illness.

PMID- 11465786
TI  - Predictors of incident care service utilisation for mental health problems in the
      Dutch general population.
AB  - BACKGROUND: The determinants of first-time ('incident') use of primary care and
      mental health care services for mental health problems have not been previously
      investigated. Such information is needed to identify new client groups and to
      gain a better understanding of causal factors. METHOD: Data were derived from the
      Netherlands Mental Health Survey and Incidence Study, NEMESIS, a prospective
      general population study of adults. Potential predictors of care use (psychiatric
      disorders, burden of illness, sociodemographic characteristics) were recorded in
      the first wave of the study, and the utilisation of care services in the second
      wave. Psychiatric diagnoses were based on the Composite International Diagnostic
      Interview (CIDI) 1.1. RESULTS: Six of the ten indicators linked to the frequent
      utilisation of care were found not to be associated with incident use: higher
      age, lower income, living alone, paid employment, mood disorders and anxiety
      disorders. Four other indicators showed associations with both frequent and
      incident use: female gender, higher numbers of restricted activity days, poorer
      social functioning and unmet care needs. Two predictors of incident use only were
      lower educational attainment and being in treatment for a somatic disorder.
      CONCLUSION: New clients who come to primary health care or mental health care
      services with mental health problems are found in all age groups. They are more
      likely to be women, to have less education, to be in treatment for a somatic
      disorder and to have functional problems related to their mental health problems.

PMID- 11465787
TI  - Physical child abuse in Sweden: a study of police reports between 1986 and 1996.
AB  - BACKGROUND: This study aims at investigating physical child abuse in Sweden
      during 1986-1996, a period when alarm was being raised about an increased number
      of police reports on physical child abuse. The study focuses on abuse committed
      by a parent or carer and aims at analyzing the victim and the perpetrator, family
      environment, injuries and judicial consequences of physical abuse. METHOD: All
      police reports on physical child abuse (0-14 years old) in a designated police
      district in Sweden during 1986-1996 were examined, as well as any judicial
      proceedings that followed. RESULTS: Our research yielded three major findings.
      Firstly, a large part of the increased number of police reports had to do with
      violence outside the family: 145 children (0.5 per 1000 children) were found
      abused within the families, by a parent or a carer. Secondly, there was a
      tendency toward males abusing boys and females abusing girls, and the biological
      father was the most frequent suspected perpetrator. Thirdly, 20% of the police
      reports led to prosecutions, and the investigations were time consuming. Known
      risk factors for physical abuse, such as unemployment, violent spouse relations,
      substance and drug abuse and poor mental health were found in several families,
      often among the prosecuted perpetrators. When examining incidence of physical
      abuse, Sweden was comparable to the other Scandinavian countries, where
      legislation and social context are similar. CONCLUSIONS: The numbers of
      physically abused children that have been reported to the police in Sweden has
      increased during the investigated period. Familiar risk factors are present in
      our study, accompanied by new findings, such as, for instance, a gender
      preference towards the abuse victim.

PMID- 11465788
TI  - A national survey of violence experienced by community mental health researchers.
AB  - BACKGROUND: In recent years there has been a vigorous debate concerning the
      relationship between violence and mental illness. Psychiatric hospital staff are
      especially likely to experience violence. 'Detached staff' working in the
      community appear to be at greatest risk. The present study examines reported
      aggression towards field-based community mental health researchers (CMHRs). It
      aimed to investigate the nature and extent of violence experienced by CMHRs, to
      establish which CMHR characteristics act as precipitators of violent incidents
      and to identify training needs. METHODS: This national survey, conducted between
      December 1997 and March 1998 at the Department of Mental Health, University of
      Exeter, used a postal questionnaire circulated among CMHRs working in England,
      Scotland and Wales. RESULTS: Whilst this study did not achieve comprehensive
      coverage of all eligible CMHRs, it indicates that, even allowing for response
      bias, occupational violence is not uncommon among CMHRs: 51% (n = 33) ever
      experienced at least one verbally violent incident, 9% (n = 6) a mildly violent
      incident and 2% (n = 1) a severely violent incident. In the 12 months preceding
      the study, 45% of CMHRs (n = 29) had experienced at least one verbally violent
      incident and 8% (n = 5) a mildly violent incident. Male CMHRs are more likely (P
      < 0.05) to experience violence than their female counterparts. CONCLUSIONS: The
      findings indicate a need to improve existing safety training, procedures and
      awareness among this occupational group. Additional comparative research among
      other community-based groups is, however, required.

PMID- 11465789
TI  - Measurements of intraventricular pressure in a patient shunted from the ventricle
      to the internal jugular vein against the direction of blood flow (the El-Shafei
      shunt).
AB  - OBJECT: After demonstrating the anti-siphoning properties of a distensible tube
      in vitro, El-Shafei constructed a shunting system that directs CSF flow into the
      internal jugular vein against the flow of blood. Though clinically effective, the
      in vivo pressure dynamics of this type of shunt system have not been
      investigated. METHODS: After failure at multiple other extracranial absorptive
      sites, an 18-year-old woman was shunted from the lateral ventricle to the
      internal jugular vein against the direction of blood flow. The shunt system
      contained an in-line noninvasive telemonitor allowing examination of postural
      intracranial pressure dynamics in the awake state. This shunt system demonstrated
      postural pressure dynamics that were consistent with a stringent nonsiphoning
      shunting system. CONCLUSIONS: These observations validate the use of the El
      Shafei shunt placement as a biologically nonsiphoning CSF absorptive system. In
      addition, the stringency of the anti-siphoning properties of the internal jugular
      vein open the possibility of preferentially using this shunting system in
      patients who clearly exhibit symptoms of shunt overdrainage.

PMID- 11465790
TI  - Assessment of intracranial pressure volume relationships in childhood: the lumbar
      infusion test versus intracranial pressure monitoring.
AB  - OBJECT: This study was undertaken to compare the results of two tests that are
      widely used to assess intracranial pressure-volume relationships in children: the
      lumbar steady state infusion test providing information about the resistance to
      cerebrospinal fluid (CSF) outflow (Rout), and continuous intracranial pressure
      (ICP) monitoring. METHODS: The study included 28 children aged 5-91 months, on
      whom both tests were performed. The median duration between the tests was 1
      month. With the child in general narcosis, the lumbar CSF pressure was recorded
      before and during infusion of artificial CSF, and the Rout was calculated on the
      basis of the opening (Po) and plateau (Pp) pressures (Rout=Pp-Po/infusion rate).
      ICP was recorded every 5 s using a computer-based system. CONCLUSIONS: We found
      no significant correlation between Rout and mean ICP asleep. There were no
      significant relationships between abnormal mean ICPs during sleep (defined as
      either 10 or 15 mmHg) and abnormally high Rout values (defined as either 10 or 12
      mmHg/ml/min), and no significant relationships between abnormally high Rout
      values (10 or 12 mmHg ml(-1) min(-1)) and the presence of abnormal ICP elevations
      (defined as either 20 or 25 mmHg and lasting 5 min). Therefore the calculation of
      Rout by the infusion test performed on children under general anesthesia gave no
      reliable prediction of abnormal ICP.

PMID- 11465791
TI  - Neuroendoscopic third ventriculostomy in dysmorphic brains.
AB  - Neuroendoscopic third ventriculostomy (NTV) has superseded shunting as the
      treatment of choice in non-communicating hydrocephalus. Intracranial
      developmental anomalies have been considered to be relative contraindications for
      this procedure. We present one patient with a Dandy-Walker malformation and
      another with septo-optic dysplasia who presented with hydrocephalus. An NTV was
      performed successfully in both patients using a flexible neuroendoscope and
      utilising transendoscopic Doppler ultrasound to ensure a safe target area for
      ventriculostomy.

PMID- 11465792
TI  - Ascites following ventriculoperitoneal shunting in children with chiasmatic
      hypothalamic glioma.
AB  - OBJECT: Optic pathway gliomas in children can involve the optic nerve, chiasm,
      and hypothalamus. This uncommon, slowly growing tumor can cause hydrocephalus,
      which usually requires placement of a ventriculoperitoneal (VP) shunt.
      Symptomatic ascites may occasionally develop as a complication of the VP shunt
      procedure. The purpose of this study was to assess the risk factors associated
      with CSF ascites in children with optic pathway gliomas. METHODS: Twenty-two
      children (ages 4 months to 20 years) with chiasmatic-hypothalamic optic gliomas
      participated in this study. Four children were diagnosed with a chiasmatic
      glioma, 7 with a hypothalamic glioma, and 11 with a glioma involving both the
      optic chiasm and hypothalamus. Twelve children (55%) developed hydrocephalus and
      required VP shunt placement. Of the 12 shunted children, 4 (33%) developed CSF
      ascites. The incidence of ascites was not associated with infection, tumor
      metastasis, or multiple shunt revisions. There was no correlation with the size
      of the tumor. All 4 children with ascites had tumor involving the optic chiasm or
      optic nerve. None of the 5 children with pure hypothalamic glioma who underwent
      VP shunt placement have developed ascites. Among the 7 children suffering from
      chiasmatic or optic nerve gliomas who developed hydrocephalus, the risk of
      developing ascites as a complication of VP shunt placement was 57% (4/7).
      Ventriculoatrial (VA) shunt was the treatment of choice for children with VP
      shunt-induced ascites. After placement of a VA shunt the ascites subsided. The
      children did not develop further complications. CONCLUSION: We conclude that
      glioma involving the optic chiasm or nerve is associated with a high risk of
      developing ascites following VP shunt placement. VA shunt may be the treatment of
      choice for children with chiasmatic or optic nerve gliomas who require a CSF
      diversion procedure.

PMID- 11465793
TI  - Comparative effects of valproic acid sodium for Chiari-like malformation at 9 and
      10 days of gestation in the rat.
AB  - Our study was conducted to compare structural changes of brain exposed to 500
      mg/kg valproic acid sodium (VA) at 10 days of gestation and 2x600 mg/kg VA at 9
      days of gestation for Chiari-like malformation (CLM). Brains, each still in the
      cranium, were placed under the dissecting microscope in such a way that the
      midsagittal surface for angular morphology was seen, and video images were
      recorded for both study groups. Distances and angles in each brain were then
      measured on video image photographs both manually and by means of a computer. The
      vertebral arch distances following exposure to 500 mg/kg VA at 10 days of
      gestation were measured. VA on day 9 of gestation group was not followed by
      significantly different angular morphology or point-to-point distances from those
      in fetuses exposed to saline. In contrast, the angle formed between the frontal
      pole and cerebellum at the pons is more -acute in animals treated with VA 500
      mg/kg on day 10 of gestation than in controls, but the distances were not
      reduced. However, the group exposed to VA 500 mg/kg on day 10 of gestation
      appeared to have sustained only minimal effects on the vertebral arch distances;
      specifically, spina bifida aperta was not produced in this group. These analyses
      may indicate that the anterior neural tube is more sensitive to the mechanism of
      action by which VA produces neural tube defects (NTDs) than is the posterior
      neural tube. Also, we can conclude that in these rat models, experimental CLM
      does not correspond to the Chiari malformation (CM) type 2. An animal model has
      its own species specificity and teratogenic environment, and the
      embryopathogenesis of NTD in the experimental animal model may not be directly
      applicable to the human condition.

PMID- 11465794
TI  - Cerebral abnormalities in lumbosacral neural tube closure defect: MR imaging
      evaluation.
AB  - OBJECTS: It was decided that patients with caudal neural tube closure defect
      should be evaluated by means of cranial MR scans, with special attention devoted
      to cerebral malformations other than craniospinal abnormalities. METHODS: Twenty
      four patients with lumbosacral neural tube closure defects, classified into
      myeloschisis (MS, 9 cases), meningo(myelo)cele (MMC, 10 cases) and spina bifida
      occulta with lumbosacral lipoma (LL, 5 cases), were evaluated in this way, and
      cerebral anomalies were found to be present in all MS patients, 8 with MMC and 2
      with LL. The cerebral hemispheres were mildly to moderately hypoplastic in 6
      patients, and hydrocephalus was present in 6 patients with MS and in 5 with MMC;
      LL was not associated with ventriculomegaly in any patient. Polymicrogyria was
      present in 6 patients with MS, in 3 with MMC, and in none of those with LL.
      Heterotopic gray matter was observed in only 2 patients with MS. Partial agenesis
      of the corpus callosum was found in 6 MS patients and in 6 patients with MMC, but
      was not seen in patients with LL. Cervicomedullary anomalies, such as herniation
      of the cerebellar tonsils through the foramen magnum, were found in 7 patients
      with MS, in 4 with MMC and in 2 with LL. While patients with LL were accompanied
      by only mild forebrain anomalies, cerebral abnormalities in MS and MMC were
      generally more severe in degree than those in LL. Among 21 patients in whom
      intellectual and performance status was evaluated, 9 of the 17 patients with
      cerebral anomalies had some degree of retardation, and the 4 without cerebral
      anomalies were normal. CONCLUSIONS: Caudal neural tube closure defect is not a
      single developmental abnormality, and can be regarded as one part of the spectrum
      of malformations causing primary insults that are as yet unidentified to the
      developing central nervous system.

PMID- 11465795
TI  - Aneurysmal bone cyst of the temporal bone.
AB  - Aneurysmal bone cysts are uncommon lesions of the bone, which are benign and non
      neoplastic in nature. They are commonly seen in the long bones. Their occurrence
      in the calvarium is rare. We report the occurrence of an aneurysmal bone cyst in
      the temporal bone of a young boy, which eroded the posterior part of the orbit to
      cause proptosis.

PMID- 11465796
TI  - Diminished plantar grasp response as an additional indicator of a shunt
      malfunction in a case of congenital hydrocephalus.
AB  - A male infant with congenital hydrocephalus who had undergone
      ventriculoperitoneal (VP) shunting at 3 days of life exhibited a diminished
      plantar grasp response (PGR) from 2 months of age, which had clearly recovered 3
      months after a shunt revision at 6 months of age. The diminished PGR was the only
      overt neurological sign in this patient. The precipitous decrease in PGR that
      occurs during early infancy in a hydrocephalic infant with VP shunting is a
      possible indicator of a prespastic condition caused by a shunt malfunction.

PMID- 11465797
TI  - Childhood subarachnoid hemorrhage associated with fibromuscular dysplasia.
AB  - A rare case of childhood subarachnoid hemorrhage (SAH) is reported. A 5-year-old
      boy presented with SAH. A cerebral angiogram showed obstruction of the first
      segment of the left anterior cerebral artery (A1). The A1 was surgically trapped
      to prevent rebleeding. Proliferation of myofibroblasts was revealed in the intima
      of the A1. Cerebral infarction appeared in the territory of the left middle
      cerebral artery (MCA) on day 2 after onset of SAH, and the patient suffered a
      second SAH on day 26. The second angiogram showed stenosis and a saccular
      aneurysm in the left MCA. A second surgery, neck clipping of the aneurysm, was
      needed. The multiple arterial lesions and histological findings indicated that
      the SAHs and the infarction were caused by the dissecting aneurysm affected with
      fibromuscular dysplasia (FMD). Intracranial FMD is mainly detected in children
      and causes cerebral ischemia and bleeding. Surgical treatment of childhood SAH
      should be discretely chosen with due consideration for FMD.

PMID- 11465798
TI  - Intracranial hemorrhage associated with congenital organic disease in neonates.
      Report of two cases and review of literature.
AB  - We report on two patients with intracranial hemorrhage associated with primary
      organic lesions who underwent surgery within 24 h after birth. The primary
      lesions in the two cases were an arteriovenous malformation (AVM) and a brain
      tumor. The patient with AVM has exhibited normal growth without neurological
      deficits during follow-up over 18 years, but the patient with brain tumor has
      exhibited various degrees of neurological deficits and developmental retardation.
      Timely diagnosis and aggressive surgery may be required for the management of
      neonatal AVMs with intracerebral hemorrhage.

PMID- 11465799
TI  - Reversible encephalopathy associated with tacrolimus in pediatric renal
      transplants.
AB  - Neurological complications post transplant have been described with the use of
      calcineurin inhibitors. Although tacrolimus may be a better immunosuppressant
      than cyclosporine, its neurological side effects may be worse. Two children,
      living-related kidney transplant recipients, were treated with antibody
      induction, mycophenolate mofetil, prednisone, and tacrolimus. Soon after
      transplant, they each developed an encephalopathy, which when visualized by
      magnetic resonance imaging showed that it affected both white and grey matter of
      the brain. Although the encephalopathy was associated with the use of tacrolimus,
      there was a complete neurological recovery without cessation of the drug.

PMID- 11465800
TI  - Ulcerative colitis in a renal transplant patient with previous Goodpasture
      disease.
AB  - A renal transplant was performed in a 6-year-old boy who developed end stage
      renal disease (ESRD) after presenting with antiglomerular basement membrane (anti
      GBM) disease. At 10 years of age he developed ulcerative colitis while being
      immunosuppressed with cyclosporin, prednisone, and azothioprine. He had a
      pancolectomy, and at 14 years has no symptoms of ulcerative colitis or anti-GBM
      disease. HLA typing revealed that he was homozygous for HLA DR2. The co
      occurrence of anti-GBM disease and ulcerative colitis has not previously been
      described. Although there is no known common etiology for these two autoimmune
      diseases, we propose that the patient's homozygosity at HLA DR2 may have
      predisposed him to both.

PMID- 11465801
TI  - Immediate post-transplant nephrosis in a patient with congenital nephrotic
      syndrome.
AB  - A 19-month-old girl with congenital nephrotic syndrome of the Finnish type
      underwent a living-related renal transplant; 24 h after transplantation she
      became massively nephrotic. She did not respond to steroids, plasmapheresis, and
      high-dose cyclosporine. A month later, a renal biopsy showed only glomerular foot
      process effacement. She was treated with high-dose methylprednisolone pulses and
      oral cyclophosphamide. She rapidly went into complete remission with no further
      relapses. Graft function has been stable 2 years after transplantation.

PMID- 11465802
TI  - Branchio-oto-renal syndrome: identification of a novel mutation in the EYA1 gene.
AB  - Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized
      by the association of branchial cysts or fistulae, external ear malformation
      and/or preauricular pits, hearing loss, and renal anomalies. Mutations in the
      EYA1 gene, a human homologue of the Drosophila 'eyes absent' gene, have been
      identified as cause of the syndrome. We report here two families with BOR
      syndrome. In one family, with the complete phenotype, a novel splice site
      mutation in exon 15 (1599 +1 G to A) is described. No mutations in the EYA1 gene
      were found in a second family presenting with ear pits, deafness, and renal
      anomalies, but lacking branchial fistulae. These and other findings from the
      literature suggest the existence of genetic heterogeneity of the BOR, BO, and
      other related phenotypes, with two or more genes involved.

PMID- 11465803
TI  - Successful plasma therapy in hemolytic uremic syndrome with factor H deficiency.
AB  - A patient with homozygous factor H deficiency presented with hemolytic uremic
      syndrome (HUS) at the age of 7 months. After a 2-year period of stability, renal
      failure and erythrocyte fragmentation recurred between the age of 3 and 4 years.
      Fresh frozen plasma infusions allowed renal function to be improved and
      erythrocyte fragmentation to be stopped. Withdrawal of plasma therapy led to a
      relapse of the biological signs of HUS.

PMID- 11465804
TI  - Acquired glomerulocystic kidney disease following hemolytic uremic syndrome.
AB  - Glomerulocystic kidney disease (GCKD) is a rare congenital condition that is
      usually reported in infants and young children. Only five cases of acquired GCKD
      after an acquired renal disease have been reported. Among these, two patients
      have developed cystic glomerular lesions following hemolytic uremic syndrome
      (HUS). We report a third case in a 2-year-old patient with this association.
      Common features between these three cases include atypical HUS, development of
      GCKD after prolonged peritoneal dialysis treatment, severe hypertension, and
      normal-sized kidneys without development of macroscopic cysts. Pathology findings
      in our patient include heavy expression of epidermal growth factor receptor in
      proximal tubules and evidence of obstruction of the glomerular outflow. We
      speculate that cystic dilatation of the Bowman's capsule may be secondary to
      ischemic lesions leading to proximal tubular obstruction.

PMID- 11465805
TI  - Glomerular CD8+ cells predict progression of childhood IgA nephropathy.
AB  - The aim of this study was to evaluate whether the infiltrating T-lymphocyte can
      be a predictor in the disease progression of IgA nephropathy (IgAN). Twenty
      children with IgAN, followed for more than 5 years, were divided into progressive
      (n=5) and non-progressive groups (n=15). We assessed glomerular and interstitial
      infiltration of T-lymphocytes (CD4+ and CD8+ cells) and expression of alpha
      smooth muscle actin (alpha-SMA) and transforming growth factor-beta (TGF-beta)
      using an indirect immunofluorescence method on the renal biopsies. We analyzed
      their relationship to the degree of proteinuria, histological changes, and
      prognosis. The number of CD8+ cells in glomeruli and in interstitium was higher
      in the progressive group than in the non-progressive group. The glomerular alpha
      SMA staining was more intensive in the progressive group than in the non
      progressive group. Urinary protein and the degree of histological changes were
      also higher in the progressive group than in the non-progressive group. Among
      these markers, the number of glomerular CD8+ cells was the most apparent
      difference between the two groups. In conclusion, these results indicate that the
      number of glomerular CD8+ cells is the most sensitive predictor of disease
      progression in childhood IgAN.

PMID- 11465806
TI  - Adaptation of renal function after unilateral nephrectomy in children with renal
      tumors.
AB  - Following treatment, survivors of unilateral Wilms tumor (WT) develop structural
      and functional changes in the remnant kidney. A disproportional increase in
      functional over structural changes results in hyperfiltration, a condition that
      may lead to renal damage. We studied adaptation of renal function after
      uninephrectomy in ten WT patients and a child with renal cell carcinoma.
      Glomerular filtration rate (GFR) (measured by inulin and creatinine clearances),
      renal plasma flow (RPF) by para-aminohippurate (PAH) clearances and segmental
      tubular Na+ transport were studied before and following a protein load (renal
      functional reserve). Nine patients showed a well-adapted kidney function with a
      GFR of 82.27 (+/- 5.6), an RPF of 429.71 (+/- 65.6) ml/min/1.73 m2 and a
      filtration fracton (FF) of 20%. Absolute proximal Na+ reabsorption was 65.2 (+/-
      9.6) ml/min/1.73 m2, distal tubular delivery was 18.2 (+/- 3.9) ml/min/1.73 m2
      and absolute distal Na+ reabsorption was 2146 (+/- 435) microM/min. A peculiar
      finding was the high baseline creatinine clearances (176.17 ml/min/1.73 m2)
      related to increased baseline tubular creatinine secretion. Over 120 min
      following the protein load, GFR increased by 20%, RPF by 6% and FF remained
      unchanged. Absolute proximal reabsorption increased by 20% and distal
      reabsorption by 22%. While most changes in renal function induced by a protein
      load are similar in healthy individuals and uninephrectomized patients, a more
      predominant contribution to Na+ reabsorption by the proximal tubule was noted.
      Postload fractional proximal reabsorption remained at 77% while in healthy
      persons a decrease from 77% to 62% was reported. Two patients showed
      dysfunctional changes following nephrectomy characterized by an increased GFR
      (130 ml/min/1.73 m2), increased filtration fraction (29%) and inability to
      increase glomerular and tubular functions following a protein load (loss of
      functional reserve). The significance of these abnormalities is not known and
      requires long-term follow-up to evaluate whether hyperfiltration will lead to
      renal damage.

PMID- 11465807
TI  - Fetal renal hyperechogenicity in intrauterine growth retardation: importance and
      outcome.
AB  - The object of the study was to investigate the outcome in growth-retarded
      newborns who were diagnosed with fetal renal hyperechogenicity without anatomical
      abnormality during any stage of pregnancy. Depending on the fetal renal
      ultrasonography result, the cases were divided into two study groups. There was
      an intrauterine growth-retarded group with fetal renal medullary
      hyperechogenicity and another group without fetal renal medullary
      hyperechogenicity. The renal parenchyma was observed after birth, within the
      first 5 days of life, and several times until the 14th postpartum day in positive
      cases. Hyperechogenic renal medullae were detected in 25 of 90 cases with
      intrauterine growth retardation during the 8-month study period. This may be an
      in utero cause of subsequent intrauterine and neonatal complications, such as
      cesarean section because of fetal distress (36%), perinatal infection (24%),
      treatment in a neonatal intensive care unit (52%), or increased perinatal
      mortality (8%). The results demonstrate that fetuses with hyperechoic medullae
      had 1.5 times the risk of an abnormal outcome compared with fetuses with normal
      echoic kidneys and intrauterine growth retardation. Detailed ultrasound
      examinations of renal parenchyma appear to be useful for the prenatal diagnosis
      of intrauterine hypoxia, allowing the detection of possible pathological fetal
      conditions in utero.

PMID- 11465808
TI  - Prognostic significance of distal renal tubular acidosis in posterior urethral
      valve.
AB  - The prognostic significance of distal renal tubular acidosis (DRTA) in the
      development of overt nephropathy (ON) in children with posterior urethral valves
      (PUV) is not clear. This condition was studied prospectively in 22 children with
      posterior urethral valve (PUV), with normal renal function. Prior to surgery, the
      children with ON had a higher incidence of bilateral reflux (P=0.006), but the
      difference was not significant for age at surgery (P=0.31), duration of voiding
      symptoms prior to surgery (P=0.30), presence of DRTA (P=0.35) and bladder
      abnormalities (P=0.27), with none of these factors being significant on logistic
      regression analysis. At the end of the follow-up, after surgery, age at surgery
      (P < or = 0.0001), duration of voiding symptoms prior to surgery (P < or =
      0.0003), persistent DRTA (P=0.0001) and persistent bladder dysfunction (P=0.02)
      after surgery were significantly higher in children with ON. On univariate
      logistic regression analysis, age at surgery (P=0.009), duration of voiding
      symptoms prior to surgery (P=0.01), persistent DRTA (P=0.002) and persistent
      bladder abnormalities (P=0.03) after surgery were significant for ON after
      surgery, but on stepwise multivariate logistic regression analysis only
      persistent DRTA (P=0.002) turned out to be significant. We conclude that
      persistent DRTA after surgery can predict overt nephropathy in children with PUV
      after surgery.

PMID- 11465809
TI  - Cisplatin nephrotoxicity in children after continuous 72-h and 3x1-h infusions.
AB  - Little is known about the association between the rate of cisplatin
      administration and the severity of cisplatin-induced renal damage in children.
      The purpose of this study was to compare severity and reversibility of renal
      damage in children after continuous and repetitive bolus administration of
      cisplatin and to correlate these data with pharmacokinetic parameters. Study
      subjects included six children (ten courses) receiving cisplatin as 1-h bolus
      infusions on three consecutive days (3x40 mg/m2) and four children (eight
      courses) receiving 72-h continuous infusions (120 mg/m2). In all courses, signs
      of glomerular and tubular damage were seen, as evidenced by elevated urinary
      excretion of alpha1-microglobulin, albumin and N-acetyl-beta-D-glucosaminidase
      and decreased glomerular filtration rate (GFR). Comparing the two infusion
      regimens, the 1-h bolus administration of cisplatin was followed by significantly
      higher peak free platinum concentrations in plasma and urine (P<0.001), resulting
      in lower nadirs of the GFR (P<0.005). Correlations were found between both peak
      free platinum concentrations in plasma and urine and maxima of urinary albumin
      and N-acetyl-beta-D-glucosaminidase excretion. Within 12 months after completion
      of cisplatin therapy, children in the 1-h bolus group had recovered only
      partially from subclinical nephrotoxicity, with five out of six showing
      pathological proteinuria. The results provide clear evidence that long-term
      ciplatin infusions are less nephrotoxic than repetitive bolus infusions.

PMID- 11465810
TI  - Amphotericin B-induced partial nephrogenic diabetes insipidus in a child.
AB  - The case of a 12-year-old boy who developed polyuria and polydipsia while on
      amphotericin B treatment is discussed. The clinical and laboratory features are
      most consistent with partial nephrogenic diabetes insipidus. Several adult
      patients have been reported with amphotericin B-induced nephrogenic diabetes
      insipidus. To the knowledge of the authors, this is the first pediatric patient
      described with this condition. Pharmacological doses of antidiuretic hormone in
      conjunction with diuretic treatment significantly reduced the polyuria and
      alleviated the associated symptoms. The authors propose that in amphotericin B
      induced partial nephrogenic diabetes insipidus, pharmacological doses of
      antidiuretic hormone may offer an additional benefit to commonly used diuretic
      therapy.

PMID- 11465811
TI  - Recurrence of acute poststreptococcal glomerulonephritis.
AB  - Recurrence of acute poststreptococcal glomerulonephritis (APSGN) is a rare
      phenomenon. We present an 8-year-old boy with a second episode of APSGN 12 months
      following a complete clinical recovery from his initial attack. Renal histology,
      obtained from renal biopsies of the patient during the second attack, showed
      diffuse endocapillary proliferation, granular deposition of C3, IgG, IgA, and
      fibrinogen along capillary walls, and subepithelial electron-dense deposits. A
      new streptococcal cytoplasmic antigen (nephritis-associated plasmin receptor
      protein, NAP1r), which was recently identified as the pathogenic antigen in
      APSGN, was detected in the glomeruli of an early kidney biopsy specimen from the
      patient during the second attack of APSGN, using fluorescein isothiocyanate
      labeled rabbit anti-NAP1r. However, antibodies against NAP1r, examined by Western
      blotting, were not present in sera from the patient. These results suggest that
      recurrence of APSGN in some patients may be caused by an absence of a natural
      immune response to NAP1r.

PMID- 11465812
TI  - Posterior leukoencephalopathy syndrome in poststreptococcal acute
      glomerulonephritis.
AB  - Reversible posterior leukoencephalopathy syndrome is an increasingly recognized
      brain disorder most commonly associated with hypertension, toxemia of pregnancy,
      or the use of immunosuppressive agents. Its clinical features include headache,
      decreased alertness, mental abnormalities, such as confusion, diminished
      spontaneity of speech, changed behavior ranging from drowsiness to stupor,
      seizures, vomiting, and abnormalities of visual perception like cortical
      blindness. Magnetic resonance imaging shows edematous lesions primarily involving
      the posterior supratentorial white matter and corticomedullary junction. We
      describe a 7-year-old uremic girl who developed neurological symptoms of
      posterior leukoencephalophaty syndrome during the course of acute
      poststreptococcal glomerulonephritis. Since the symptoms first appeared 24 h
      after a hypertensive crisis and the patient was uremic at the time of symptoms,
      we decided to report this patient to discuss the differential diagnosis of
      neurological symptoms developing during the course of acute poststreptococcal
      glomerulonephritis.

PMID- 11465813
TI  - Persistent arterial hypotension after bilateral nephrectomy in a 4-month-old
      infant.
AB  - A patient with congenital nephrotic syndrome underwent bilateral nephrectomy at
      the age of 4 months. She showed persistent hypotension from the fourth
      postoperative day until death at the age of nearly 5 months. No cause for the
      hypotension could be found. It is postulated that, especially in young infants, a
      deficiency of renin after bilateral nephrectomy may cause persistent hypotension.
      An explanation for the putative increased risk of this complication in young
      infants may be their need for a highly active renin-angiotensin system. Until
      more is known about the incidence of this complication and its predisposing
      factors, reluctancy towards the performance of bilateral nephrectomy in children
      under the age of 6 months is warranted.

PMID- 11465814
TI  - Clinical quiz. Schimke immunoosseous dysplasia syndrome (SIOD).

PMID- 11465815
TI  - Another example of spontaneous improvement in a case of dense deposit disease.

PMID- 11465816
TI  - Diagnosis of recurrent intermittent airway obstruction ("recurrent croup") in
      children.
AB  - Children with a history of recurrent intermittent airway obstruction can present
      with a constellation of signs and symptoms labeled by their primary care
      physician as "recurrent croup." Recurrent croup, however, is not a diagnosis and
      should alert the clinician to the potential for intrinsic or extrinsic
      laryngotracheal pathology. This study was undertaken to evaluate referral
      patterns, diagnostic algorithms, and diagnoses for children with a history of
      recurrent intermittent airway obstruction initially characterized as "recurrent
      croup." We performed a retrospective analysis of office and operative records of
      children with a history of recurrent intermittent airway obstruction
      characterized as "recurrent croup." The setting was a university-based pediatric
      otolaryngology practice with both urban and suburban referral patterns. The
      medical records of 53 children (median age, 2 years) with a history of mild to
      severe recurrent intermittent airway obstruction characterized as "recurrent
      croup" were evaluated with respect to referral source, duration of signs and
      symptoms, diagnostic algorithm, and findings. We conclude that recurrent
      intermittent airway obstruction in children is an underappreciated clinical
      scenario. Upper aerodigestive tract endoscopy is a key component in a diagnostic
      evaluation to ascertain the cause. The decision for an endoscopic evaluation is
      best determined after analysis of the patient's age, past medical history,
      clinical severity, and suspected diagnosis. By virtue of his or her knowledge of
      aerodigestive tract anatomy and endoscopy skills, the otolaryngologist can take a
      proactive role in arriving at an accurate diagnosis in these children.

PMID- 11465817
TI  - Association of laryngopharyngeal reflux disease and subglottic stenosis.
AB  - Laryngopharyngeal reflux (LPR) disease and extraesophageal manifestations of
      gastroesophageal reflux have been recognized to have dramatic effects in the
      upper airways. Patient-reported symptoms alone underestimate the presence of LPR,
      making accurate clinical diagnosis difficult. Many previous studies examine
      populations with only standard dual-probe pH testing that does not include a test
      probe in the pharynx. Therefore, documentation of acid exposure at the laryngeal
      inlet is lacking. In adult patients with subglottic stenosis (SGS), whether due
      to granulomatous disease or presumed idiopathic causes, LPR is often a
      contributing or causative factor. A retrospective chart review from 1991 to 1999
      identified 19 patients with SGS. Ten of the 19 patients had concomitant disease
      states, including sarcoidosis (3), Wegener's granulomatosis (3), laryngeal trauma
      (3), and a history of intubation (1). Fourteen patients underwent 24-hour
      ambulatory pH probe testing with 3- or 4-port probes. The proximal port in either
      catheter was positioned by manometric guidance directly behind the laryngeal
      inlet. Measurements of pH of less than 4 were recorded at the level of the larynx
      in 12 of the 14 patients tested (86%). This finding was noted in half of the
      patients despite empirical therapy with proton pump inhibitors at the time of the
      testing. Seven of 10 patients with underlying disease were studied, and all
      demonstrated acid reflux in the hypopharynx. In 9 patients, the stenosis was
      presumed to be idiopathic. Five of the 7 patients (71%) with idiopathic SGS
      tested had positive pH probe studies (pH below 4 in the pharyngeal probe). Our
      results demonstrate a strong association of LPR and SGS. In the idiopathic group,
      reflux is the probable cause of their stenosis. In the group of patients with
      underlying disease states, reflux was involved in all tested patients and likely
      acts as a synergistic factor that stimulates their granulomatous disease to react
      and subsequently result in the development of stenosis. Evaluation for LPR with
      pharyngeal pH testing should be performed in all patients with SGS.

PMID- 11465818
TI  - Tracheoesophageal puncture in the office setting with local anesthesia.
AB  - Tracheoesophageal puncture (TEP) with voice prosthesis placement is currently the
      method of choice for vocal rehabilitation of patients who have undergone total
      laryngectomy. Occasionally, secondary TEP needs to be performed. We have used a
      TEP technique that is performed in the clinic setting with local anesthesia and
      no sedation. The purpose of this study was to review our technique and experience
      and to evaluate results, complications, and patients' acceptance of the
      procedure. We performed a retrospective chart review of the records of 14
      patients who had undergone total laryngectomy and secondary TEP placement in the
      clinic setting. The procedure was well tolerated. The voice results were fair to
      good in 11 of 12 patients. There was 1 complication, a false passage between the
      trachea and the esophagus. Voicing was immediate in 12 of the 14 cases. We
      conclude that TEP can be performed in the office setting with local anesthesia.
      The voice results are excellent, and the procedure is well tolerated by the
      patient. Proper patient selection and regular follow-up by a speech-language
      pathologist are important.

PMID- 11465819
TI  - Pediatric laryngoscopes: design and application.
AB  - Examination of the upper aerodigestive tract for diagnosis and treatment has
      become more important in pediatric otolaryngology. Techniques of endoscopy have
      improved, anesthesia is safer, and there are many specialized laryngoscopes
      designed specifically for the small, sensitive airways of infants and children.
      Knowledge of the design advantages, specifications, and applications, including
      the use of telescopes and the operating microscope, will assist in selection of
      the appropriate laryngoscope for optimum exposure.

PMID- 11465820
TI  - Chromosomal abnormalities in idiopathic congenital bilateral vocal cord
      paralysis.
AB  - Idiopathic congenital bilateral vocal cord paralysis (BVCP) can occur as an
      isolated abnormality or as part of a multisystem disorder. The chromosomal
      abnormalities found in 4 children who presented with idiopathic congenital BVCP
      in association with other congenital abnormalities between January 1991 and April
      1999 are described. Three children had abductor paralysis, and tracheostomy was
      required in 1. The fourth child had adductor paralysis and required a feeding
      gastrostomy for management of aspiration. There was no clinically significant
      improvement in vocal cord function observed in any child. Idiopathic congenital
      BVCP, when associated with other congenital disorders, may occur as a consequence
      of an underlying chromosomal abnormality, and chromosome studies should be
      performed in this group of children. Similarly, the possibility of vocal cord
      dysfunction should be considered in children who are found to have chromosomal
      abnormalities. A chromosomal abnormality appears to preclude the possibility of
      early spontaneous improvement in vocal cord function.

PMID- 11465821
TI  - Evaluation of voice quality in adductor spasmodic dysphonia before and after
      botulinum toxin treatment.
AB  - In this prospective study, the efficacy of botulinum toxin (Botox) injections in
      patients with adductor spasmodic dysphonia (AdSD) was assessed by 3 different
      modalities: perceptual and acoustic analyses and subjective self-assessment. This
      was done by comparing AdSD patients' pretreatment and posttreatment values and
      comparing these values with those of normal control speakers. In contrast to most
      other studies, the posttreatment status was defined as the optimal voice quality
      as judged by the patient. The aim of the study was to assess to what extent Botox
      injections actually improve voice quality and function. The AdSD subjects rated a
      significantly improved voice quality and function after Botox treatment. However,
      the results were never within normal limits. Perceptually, the characteristic and
      severely impaired AdSD voice improved, but another "type" of pathological voice
      was detected after Botox treatment. Acoustic analyses demonstrated a significant
      improvement, as well. Nevertheless, the "optimally" treated AdSD voice still
      remained significantly deviant as compared to normal voice production. Currently,
      Botox injection is the therapy of first choice for AdSD. Although significant
      improvement could be measured in our study perceptually, acoustically, and
      subjectively, the optimal voice that was achieved never fully matched normal
      voice quality or function.

PMID- 11465822
TI  - Bronchial intraepithelial neoplastic lesions in head and neck cancer patients:
      results of autofluorescence bronchoscopy.
AB  - To determine the efficacy of autofluorescence bronchoscopy for detection of
      bronchial intraepithelial neoplastic lesions in head and neck cancer patients, we
      analyzed data from head and neck cancer patients who underwent both white light
      bronchoscopy and autofluorescence bronchoscopy for the rates of detection of
      intraepithelial neoplastic lesions. The results of the histopathologic
      examination were compared with the bronchoscopic findings. The sensitivity for
      detection of intraepithelial neoplastic lesions was calculated. Eleven moderate
      dysplasias and 3 severe dysplasias were detected during 8 of the 42 bronchoscopic
      examinations (19%) in 6 of the 24 patients (25%). The sensitivities for white
      light bronchoscopy alone and for white light bronchoscopy combined with
      autofluorescence bronchoscopy for detection of intraepithelial neoplastic lesions
      were, respectively, 21% (3 of 14) and 57% (8 of 14). In short, bronchial
      intraepithelial neoplastic lesions were found in a considerable percentage of
      head and neck cancer patients. Use of autofluorescence bronchoscopy improved the
      detection of these lesions.

PMID- 11465823
TI  - Airflow resistance of airflow-regulating devices described by independent
      coefficients.
AB  - Rehabilitation after laryngectomy includes more and more the use of airflow
      regulating devices such as shunt valves (SVs), tracheostoma valves (TSVs), and
      heat and moisture exchange (HME) filters. In determining the quality of those
      devices, airflow resistance is a very important factor. It is currently defined
      as pressure drop divided by airflow. However, for most applications, this
      definition does not result in a pressure- and airflow-independent parameter.
      Therefore, a new set of parameters is defined and applied to pressure-airflow
      curves of airflow-regulating devices. Pressure drop over TSVs and HME filters
      appears to have a squared relationship with flow. In SVs, it has a linear
      relationship. The new set of parameters describes the pressure-airflow
      relationship properly for all considered devices. In conclusion, theoretical
      predictions of flow mechanics appear to be valid for SVs, TSVs, and HME filters.
      Only 2 coefficients are necessary to describe the pressure-flow characteristics
      of these airflow-regulating devices, independent of pressure drop over and flow
      through the device.

PMID- 11465824
TI  - Oral administration of collagen conjugated with cholera toxin induces tolerance
      to type II collagen and suppresses chondritis in an animal model of autoimmune
      ear disease.
AB  - B10.RIII (H-2r) mice were orally administered cyanogen bromide peptide 11 (CB11)
      or cholera toxin B (CTB)-conjugated CB11 to induce tolerance in collagen-induced
      autoimmune ear disease. Oral administration of a high dosage of CB11 provided
      partial protection from chondritis. However, administration of a tiny amount of
      CTB-CB11 conjugate effectively suppressed chondritis. Oral administration of CTB
      CB11 conjugate did not alter the stimulation of T cells in vitro or the fine
      specificities of B cells. The oral administration of CTB-CB11 caused a higher
      level of type II collagen-specific IgG and its subclass. Interestingly, increases
      of TH1 cytokine (interferon-gamma) in Peyer's patches and of TH1/TH2 cytokines
      (interleukin-2 and interleukin-4) in lymph nodes were detected in mice that had
      been fed CTB-CB11. An increase of CD8+ T cells in the Peyer's patches with a
      decrease of CD8+ T cells in lymph nodes was seen in mice that had been fed CTB
      CB11. These results suggest that protection from chondritis by oral
      administration of minute amounts of CTB-CB11 conjugate can be achieved by a
      mechanism distinct from that of conventional oral tolerance induction.

PMID- 11465825
TI  - Myelination of the human auditory nerve: different time courses for Schwann cell
      and glial myelin.
AB  - The goal of this study was to trace the development of myelin in the human
      auditory nerve. To do this, we used the Woelcke iron-hematoxylin technique to
      stain myelin sheaths in sections from fetal temporal bones and brain stems. In
      the cochlea, aggregations of Schwann cells are seen in the modiolus and along the
      spiral lamina by the 15th fetal week. By the 22nd fetal week, dense arrays of
      stained Schwann cells are present on auditory nerve axons within the temporal
      bone. By the 24th fetal week, light myelin sheaths extend up to, but not beyond,
      the glial junction. Myelin sheaths are not present in the auditory nerve central
      to the glial junction until the 26th fetal week or later. These results
      demonstrate a gap of several weeks between the onset of Schwann cell myelination
      distally and glial myelination proximally. The period between these two events
      may represent the time of final maturation of the organ of Corti.

PMID- 11465826
TI  - Acute otitis media in Brazilian children: analysis of microbiology and
      antimicrobial susceptibility.
AB  - Between 1990 and 1995, a total of 300 children, ages 2 months to 5 years,
      received diagnoses of acute otitis media (AOM) in a hospital emergency room in
      Sao Paulo, Brazil, and were recruited for this study. The investigation was
      undertaken, first, to identify microorganisms and antimicrobial susceptibilities
      of pathogens from AOM in Brazilian children; next, to ascertain, by comparison,
      whether the isolates of Streptococcus pneumoniae have the same serotypes as those
      included in the new conjugated heptavalent pneumococcal vaccine; and last, to
      determine whether additional and/or different serotypes are needed in the vaccine
      to ensure an immunogenic response against pneumococcal pathogens for the
      indigenous children in this study. Microorganisms were isolated from ear fluid of
      192 patients (64%). The 5 most prevalent pathogens were S pneumoniae (48
      isolates; 16%), Haemophilus influenzae (21 isolates; 7%), Moraxella catarhalis
      (15 isolates; 5%), Pseudomonas aeruginosa (6 isolates; 2%), and Staphylococcus
      aureus (3 isolates; 1%). These 5 represented 93 of the 192 total isolates.
      Resistance to antibiotics was found in the 3 primary pathogens. No high-level
      resistance of S pneumoniae to penicillin was found; instead, there was high-level
      resistance to trimethoprim-sulfamethoxazole. Ten serotypes of S pneumoniae were
      isolated: 6B, 9V, 11A, 16, 18C, 19A, 19F, 23A, 23B, and 23F. Only 5 of the 10
      serotypes isolated were included in the conjugated heptavalent pneumococcal
      vaccine. Therefore, the other 5 serotypes (24 of 48 strains) should be considered
      in selecting antigens for the new vaccine.

PMID- 11465827
TI  - Paranasal sinus ventilation in healthy subjects and in patients with sinus
      disease evaluated with the 133-xenon washout technique.
AB  - Ventilation of the paranasal sinuses is of great importance in sinus
      pathophysiology. Therefore, methods of measuring sinus ventilation are important
      for the evaluation of patients with sinus disease. In the present study, a 133
      xenon washout technique was used to evaluate the ventilation of the paranasal
      sinuses in 34 healthy subjects and in 13 subjects with sinus disease (5 patients
      with nasal polyposis and 8 patients with chronic sinusitis). For this purpose, a
      133-xenon-air mixture was insufflated in each nostril and the washout of the
      radioactive gas from the paranasal sinuses was monitored with a dynamic single
      photon-emission computed tomography camera. The half-time (+/-SD) was found to be
      18 +/- 18 minutes for the maxillary sinus, 10 +/- 8 minutes for the frontal
      sinus, and 18 +/- 23 minutes for the posterior ethmoid and sphenoid sinuses in
      the healthy subjects. Repeated measurements in 18 of the healthy subjects
      indicated that the method had acceptable reproducibility according to a Bland
      Altman plot. The 133-xenon washout was not influenced by insufflation pressure,
      nasal patency, or body position. The subjects with sinus disease exhibited half
      times of 77 +/- 101 minutes for the maxillary sinus, 91 +/- 124 minutes for the
      frontal sinus, and 60 +/- 60 minutes for the posterior ethmoid and sphenoid
      sinuses. For patients with nasal polyposis, the half-time was significantly
      longer than that in healthy subjects, while patients with chronic sinusitis did
      not differ from healthy subjects in this respect.

PMID- 11465828
TI  - Concentrations of serum immunoglobulins and antibodies to pneumococcal capsular
      polysaccharides in patients with recurrent or chronic sinusitis.
AB  - A study was carried out to search for underlying immunoglobulin deficiencies in
      25 patients with recurrent or chronic sinusitis. The mean duration of the patient
      histories of recurrent or chronic sinusitis was 7.2 years. Concentrations of
      serum immunoglobulins and specific pneumococcal antibodies were measured in the
      patients and in 25 age- and sex-matched control individuals. The mean serum IgA
      concentration (1.6 g/L) was lower in the patients than in the control individuals
      (2.1 g/L, p = .024). On the other hand, the mean serum concentration of IgG
      antibodies to pneumococcal type 14 polysaccharide was higher in the patients
      (2.54 microg/mL) than in the control individuals (0.92 microg/mL, p = .008).
      However, elevated concentrations of IgG antibodies to pneumococcal type 14
      polysaccharide were detected mainly in patients with the highest serum IgA
      concentrations. The results suggest that in a subpopulation of patients with a
      long-lasting history of sinusitis, a low serum IgA concentration may be
      associated with a susceptibility to sinusitis.

PMID- 11465829
TI  - Effects of catecholamines on calvarial bone resorption in vitro.
AB  - Many important diseases in otolaryngology manifest through abnormal bone
      remodeling or destruction. The mechanisms for such pathological remodeling remain
      poorly understood. Bone is known to be innervated by norepinephrine-containing
      sympathetic nerves, and sympathectomy is known to induce bone resorption. The
      role, however, of norepinephrine as a potential bone-modulatory substance is
      unknown. Using the calvarial calcium release assay, we conducted the following
      experiment to evaluate the bone-modulatory activity of norepinephrine, the alpha
      agonist octopamine, and the beta-agonist isoproterenol. Each agent was tested at
      2 concentrations with and without parathyroid hormone. Norepinephrine was found
      to have no effect on calcium release. In contrast, octopamine at 10(-8) mol/L
      exerted a significant stimulatory effect on calcium release, and isoproterenol at
      10(-6) mol/L exerted a significant inhibitory effect on parathyroid hormone
      induced calcium release. The investigation suggests that a bimodal, concentration
      dependent, receptor-specific model for catecholamine-mediated modulation of bone
      resorption may operate in calvarial bone.

PMID- 11465830
TI  - Penicillin treatment failure in group A streptococcal tonsillopharyngitis: no
      genetic difference found between strains isolated from failures and nonfailures.
AB  - Despite penicillin (pcV) treatment, tonsillopharyngitis caused by group A
      streptococci (GAS) is associated with bacterial failure rates as high as 25%. The
      reason for this rate of failure is not fully understood. One explanation might be
      that certain DNA profiles of GAS strains are responsible for treatment failures.
      Using arbitrarily primed polymerase chain reaction (AP-PCR), we compared the DNA
      profiles of GAS strains from 4 patients with several treatment failures following
      pcV treatment of tonsillopharyngitis with the profiles of strains of the same T
      type from patients who were clinically and bacteriologically cured after a single
      course of pcV. The isolates were obtained during the same time period and from
      the same geographic area. Thirty-seven strains of T types 4, 12, and R28 were
      investigated. Eleven different DNA profiles could be detected with the AP-PCR
      technique. Five DNA profiles were identified as T type 12, 3 as T type 4, and 3
      as T type R28. The DNA profiles of the strains from the 4 patients with several
      treatment failures differed, but all isolates from each one of these patients
      exhibited the same or a very similar profile. The DNA profiles of the failure
      strains were also represented in nonfailure strains. Treatment failure in these 4
      patients therefore seems to be due to insufficient eradication of GAS, rather
      than to reinfection with a new strain. The finding that the same DNA profile can
      be present in both failure and nonfailure strains suggests that the treatment
      failure may be to some extent host-related and not only due to bacterial factors.

PMID- 11465831
TI  - Transtympanic penetrating injury to the internal auditory canal.

PMID- 11465832
TI  - Total inferior turbinectomy: operative results and technique.

PMID- 11465833
TI  - Total inferior turbinectomy: operative results and technique.

PMID- 11465834
TI  - Incidence and hospitalization rates of varicella and herpes zoster before
      varicella vaccine introduction: a baseline assessment of the shifting
      epidemiology of varicella disease.
AB  - BACKGROUND: A 15-year postmarketing evaluation of the impact of varicella vaccine
      on the age distribution of varicella disease is being conducted at Kaiser
      Permanente Medical Care Program, Northern California (KPMCP). We report on a
      baseline assessment of the age-specific incidence and hospitalization rates of
      varicella and herpes zoster that was conducted before vaccine introduction.
      METHODS: To assess the annual incidence of varicella, a telephone survey was
      conducted in a random sample of approximately 8,000 youths 5 to 19 years of age.
      The annual incidence of hospitalizations for varicella and herpes zoster in 1994
      was assessed with the use of the computerized database at KPMCP. RESULTS:
      Varicella annual incidence was 10.3% in 5- to 9-year-olds, 1.9% in 10- to 14-year
      olds and 1.2% in the 15- to 19-year age groups, respectively. Hospitalization
      rates among the entire KPMCP membership were 2.6 and 2.1 per 100,000 person years
      for varicella and zoster, respectively. Varicella incidence in the 15- to 19-year
      age group was higher among African-Americans than among Caucasians. CONCLUSIONS:
      Varicella rates were similar in the 5- to 9- and 10- to 14-year age groups to
      rates from other published studies conducted in 1972 to 1978, 1980 to 1988 and
      1990 to 1992; however, the rate in 15- to 19-year-olds was 2 to 4 times higher
      than published rates in the same age category.

PMID- 11465835
TI  - Human parainfluenza virus-associated hospitalizations among children less than
      five years of age in the United States.
AB  - BACKGROUND: Human parainfluenza viruses 1 through 3 (HPIV-1-3) are important
      causes of respiratory tract infections in young children. This study sought to
      provide current estimates of HPIV-1-3-associated hospitalizations among US
      children. METHODS: Hospitalizations for bronchiolitis, bronchitis, croup and
      pneumonia among children age <5 years were determined for the years 1979 through
      1997 using the National Hospital Discharge Survey. Average annual
      hospitalizations during the last 4 years of the study for each of these four
      diseases were multiplied by the proportions of each disease associated with HPIV
      1-3 infection (as previously reported in hospital-based studies) to estimate
      hospitalizations potentially associated with HPIV-1-3 infections. Seasonal trends
      in HPIV-1-3-associated hospitalizations were compared with HPIV detections in the
      National Respiratory and Enteric Virus Surveillance System, which prospectively
      monitors respiratory viral detections throughout the United States. RESULTS: The
      proportions of hospitalizations associated with HPIV infection for each disease
      varied widely in the 6 hospital-based studies we selected. Consequently our
      annual estimated rates of hospitalization were broad: HPIV-1, 0.32 to 1.59 per
      1,000 children; HPIV-2, 0.10 to 0.86 per 1,000 children; and HPIV-3, 0.48 to 2.6
      per 1,000 children. Based on these data HPIV-1 may account for 5,800 to 28,900
      annual hospitalizations; HPIV-2 for 1,800 to 15,600 hospitalizations; and HPIV-3
      for 8,700 to 52,000 hospitalizations. CONCLUSIONS: We provide broad, serotype
      specific estimates of US childhood hospitalizations associated with HPIV
      infections. More precise estimates of HPIV-associated hospitalizations would
      require large prospective studies of HPIV-associated diseases by more sensitive
      viral testing methods, such as polymerase chain reaction techniques.

PMID- 11465836
TI  - Bacteriology of acute otitis media in a cohort of Finnish children followed for
      the first two years of life.
AB  - BACKGROUND: Timely information on the bacteriology of primary, noncomplicated
      acute otitis media (AOM) may today be needed more than ever, because of the
      increasing antimicrobial resistance of its major bacterial causes and because of
      the potential of new pneumococcal and other bacterial vaccines for prevention of
      AOM. METHODS: The study followed 329 children from 2 to 24 months of age at
      scheduled healthy visits and sick visits at the study clinic. Whenever AOM was
      diagnosed during the follow-up, myringotomy was performed and middle ear fluid
      was aspirated for bacterial culture. RESULTS: At least one middle ear fluid
      sample was available from 772 AOM events; Streptococcus pneumoniae (Pnc) was
      isolated in 201 (26%), Moraxella catarrhalis (Mc) in 177 (23%) and Haemophilus
      influenzae (Hi) in 174 events (23%). The incidence of Pnc AOM peaked at 12 months
      of age, whereas the incidence of Mc AOM showed the first peak at 6 months and Hi
      AOM at 20 months. Pnc AOM showed less prominent seasonality in occurrence than Mc
      and Hi AOM. Hi was a rare cause of the first 2 AOM episodes (13%) but became
      increasingly common from the third episode on (32% on average). CONCLUSIONS: Pnc,
      Mc and Hi were almost equally common findings in AOM. Pnc seems to be the most
      pathogenic of these three, the role of Mc is increasing and Hi is clearly
      associated with recurrent AOM.

PMID- 11465837
TI  - Prevalence and rapid identification of clarithromycin-resistant Helicobacter
      pylori isolates in children.
AB  - BACKGROUND: Little is known about the prevalence of antibiotic-resistant
      Helicobacter pylori infection in children. Culture and antimicrobial
      susceptibility testing are generally time-consuming and not a routine in many
      hospitals. OBJECTIVE: To investigate the prevalence of clarithromycin-resistant
      H. pylori strains in children, to identify those isolates via rapid methodology
      and to examine the severity of gastritis caused by the antibiotic-resistant H.
      pylori isolates. METHODS: Enrolled were 245 children investigated for H. pylori
      infection by endoscopic examination. The gastric antral specimens were subjected
      to DNA extraction and polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) with primers specific to the H. pylori 23S rRNA gene.
      Conventional bacterial cultures were performed simultaneously as the diagnostic
      standard. Minimal inhibitory concentrations of clarithromycin and metronidazole
      were determined by E test. This was used as a standard to determine the
      sensitivity and specificity of the above PCR-RFLP assay. The specimens were
      processed for histologic examination and evaluated by the updated Sydney system.
      RESULTS: H. pylori was isolated in 67 of the 245 children; 12 (18%) of them were
      clarithromycin-resistant and 6 (9%) were metronidazole-resistant. No difference
      in histologic examinations was noted between the antibiotic-resistant and 
      susceptible strains. We performed PCR-RFLP with all 12 clarithromycin-resistant
      isolates: 10 had a 23S ribosomal RNA A2144G point mutation; 1 had a mixture of an
      A2143G point mutant and susceptible strains; and 1 had neither of the 2
      mutations. CONCLUSIONS: The prevalence of clarithromycin-resistant H. pylori
      isolates in Taiwanese children is 18%. PCR-RFLP had a high sensitivity (92%) and
      specificity (100%) for the clarithromycin resistance gene mutation determination.
      The dominant mutation is A2144G. PCR-RFLP provides a rapid and accurate approach
      to detect clarithromycin-resistant strains within 24 h.

PMID- 11465838
TI  - Combination therapy with saquinavir soft gelatin capsules in children with human
      immunodeficiency virus infection.
AB  - OBJECTIVES: To evaluate the pharmacokinetics, tolerance, safety and antiviral
      activity of the HIV protease inhibitor, saquinavir, formulated as soft gelatin
      capsules (SQV-SGC), given in combination with nucleoside antiretroviral agents
      (NRTIs) with or without nelfinavir in HIV-infected children. METHODS: This was an
      open label study of HIV-infected children ages 3 to 16 years, conducted in two
      parts. In Part 1 of the study 14 children were treated orally with SQV-SGC
      (initially given in three 33-mg/kg doses daily; dosage adjusted to 50 mg/kg three
      times daily based on initial pharmacokinetics) and two NRTIs. Addition of
      nelfinavir was permitted for children who did not achieve a predetermined steady
      state target plasma saquinavir exposure. In Part 2 a new group of 13 children
      received SQV-SGC (33 mg/kg three times daily) in combination with nelfinavir and
      one or two NRTIs. Pharmacokinetics were assessed after the first dose and 4 weeks
      into treatment (steady state). Patients were treated for 72 and 48 weeks in Parts
      1 and 2, respectively. RESULTS: Most adverse events were mild; the most commonly
      reported were diarrhea, abdominal discomfort and headache. Two children were
      withdrawn from the study because of adverse events (one each of nausea and
      dysphagia) related to the study treatment. There were no deaths or serious
      adverse events attributed to the study medication. Steady state saquinavir area
      under the plasma concentration vs. time curves (AUC24) were 6,210 and 11,010
      ng/h/ml for Parts 1 and 2, respectively. Compared with baseline measurements
      median changes in plasma HIV RNA concentrations were -2.12 log10 copies/ml [5 of
      14 (36%) with HIV RNA <50 copies/ml) (Week 72)] and -2.58 log10 copies/ml [8 of
      13 (62%) <50 copies/ml) (Week 48)] in Parts 1 and 2, respectively. The median
      changes in CD4+ lymphocyte count were +292 and +154 cells/microl for Parts 1 and
      2, respectively. Genotypic resistance assays revealed a low frequency of
      saquinavir-associated resistance mutations after 48 weeks of therapy, with only 2
      of 27 children having substitutions at positions 48V and/or 90M. CONCLUSIONS:
      Combination therapy with SQV-SGC was well-tolerated and safe in HIV-infected
      children, and antiviral activity was observed. Saquinavir plasma concentrations
      were lower than expected, particularly for Part 1 (SQV-SGC plus NRTIs), but
      addition of nelfinavir increased saquinavir exposures.

PMID- 11465839
TI  - Inhibition of enteroaggregative Escherichia coli adhesion to HEp-2 cells by
      secretory immunoglobulin A from human colostrum.
AB  - BACKGROUND: Enteroaggregative Escherichia coli (EAEC) is an important agent of
      the persistent diarrhea among low socioeconomic level children in developing
      countries that may be associated with chronic undernourishment. Breast-feeding is
      effective in protecting infants against diarrhea and other infectious diseases.
      The aim of the study is to verify the ability of human colostrum to inhibit
      aggregative adhesion of EAEC to HEp-2 cells and the presence of antibodies
      reactive to antigenic fractions of EAEC in colostrum samples. METHODS: Enzyme
      linked immunosorbent assay, immunoblotting and adhesion assays of EAEC to HEp-2
      cells were done with pooled or individual colostrum samples (n = 35). Assays were
      performed with a well-known EAEC strain, 044:H18 E. coli (strain 042). Colostral
      IgA was isolated by affinity chromatography in Sepharose anti-human alpha chain
      column. RESULTS: Total colostrum and isolated IgA inhibited EAEC adhesion, and
      this ability was associated with the presence of IgA antibodies against a 15-kDa
      band, compatible with the subunits of aggregative adherence fimbrial adhesin II,
      characteristic of the 042 strain, absent in its plasmid-cured isogenic strain,
      that was used as control. Individual colostrum samples also inhibited adhesion,
      showed variable antibody titles against EAEC antigens in enzyme-linked
      immunosorbent assay and recognized many antigenic fractions in immunoblotting
      assays, including the 15-kDa band. CONCLUSIONS: These results confirm that IgA
      from human colostrum inhibits adhesion of EAEC to HEp-2 cells and suggest that
      colostrum IgA antibodies reactive to EAEC antigens may play a role in protection
      of infants against diarrhea caused by these bacteria.

PMID- 11465840
TI  - Physician control of pediatric antimicrobial use in Beijing, China, and its rural
      environs.
AB  - BACKGROUND: Antibiotic resistance is recognized as an increasing problem in
      China. It is widely believed that because antibiotics are available without a
      prescription, changing physician prescribing behaviors will not decrease
      inappropriate usage. This study identified the sources of antibiotics and the
      important influence that physicians have on antibiotic use by children in one
      region of China. METHODS: Trained medical professionals surveyed parents of
      children attending several kindergartens in urban Beijing and rural Gu'An, Hebei
      County. Parents completed a questionnaire concerning the children's recent
      illnesses, care-seeking patterns and antibiotic use. The team also observed
      hospital- and non-hospital-based pharmacy purchases of antibiotics for children,
      assessed the proportion accompanied by a prescription and then interviewed
      parents about factors influencing those purchases. RESULTS: Of 241 urban and 143
      rural kindergarten parents, 76 to 82% usually obtained children's antibiotics
      from a hospital pharmacy (with a prescription). For 84% the first source of care
      was usually a physician (primarily western medicine, sometimes traditional
      Chinese medicine). Only 5% of antibiotics were obtained from independent vendors
      without prior physician consultation. Among 229 observed antibiotic purchases 72%
      occurred at hospital-based facilities, even after longer observation times at
      nonhospital pharmacies. Prescriptions accompanied all hospital-based antibiotic
      purchases, contrasting with 18% of nonhospital transactions (P < 0.001). Together
      86% of parents self-reported that the observed purchase stemmed from a doctor's
      recommendation. CONCLUSIONS: Doctors directly and indirectly controlled the
      majority of antibiotic usage for childhood illnesses in Beijing and Gu'An (Hebei
      County). Physician education and implementation of treatment guidelines might
      substantially reduce inappropriate antimicrobial usage and help prevent
      antimicrobial resistance in this region.

PMID- 11465841
TI  - Rotavirus-associated medical visits and hospitalizations in South America: a
      prospective study at three large sentinel hospitals.
AB  - BACKGROUND: Knowledge of the impact of rotavirus-associated disease on the health
      care systems of South America can aid in defining strategies for diagnosis,
      management and prevention. Up to date information on the impact of rotavirus
      disease in South America is scarce. AIM: To determine prospectively the impact of
      rotavirus disease as a cause of medical visits and hospitalizations at three
      large sentinel pediatric hospitals in Argentina, Chile and Venezuela. METHODS: A
      2-year prospective surveillance for rotavirus-associated medical visits and
      hospitalizations was conducted during 1997 through 1998 at three large sentinel
      public hospitals, one each in Argentina, Chile and Venezuela. A common
      surveillance protocol was implemented at the three sites, and a representative
      number of nonbloody diarrhea stool samples from children <36 months of age were
      tested for rotavirus by enzyme-linked immunosorbent assay. RESULTS: For our
      target age group, acute diarrhea-associated medical visits/hospitalizations
      represented 41%/2%, 5%/6% and 9%/13% of all medical visits/all hospitalizations
      at the Argentinean, Chilean and Venezuelan sites, respectively (P < 0.001 for
      difference among the three sites). Rotavirus detection rates among a total of
      5,801/1,256 medical visit/hospitalization diarrhea stool samples tested were
      39%/71% in Argentina, 34%/47% in Chile and 29%/38% in Venezuela (P < 0.01 by chi
      square for difference among the three sites). Rotavirus was associated with a
      mean of 1.5, 1.8 and 3% of total medical visits and 1.6, 2.8 and 5% of
      hospitalizations among children <36 months of age at the Argentinean, Chilean and
      Venezuelan sites, respectively. Seasonality was evident for medical visits at all
      three sites (although less striking in Chile) with peak activity occurring
      between November and May. Rotavirus-associated hospitalizations had a marked peak
      in Venezuela, represented largely by short stays, but not in Argentina and Chile.
      CONCLUSIONS: Rotavirus was a significant cause of medical visits at all three
      sentinel sites. Rotavirus caused less hospitalizations than previously reported
      in Argentina and Chile. On the basis of our findings we estimate that
      approximately 106,000/ 21,000, 48,000/8,000 and 98,000/31,000 rotavirus
      associated medical visits/hospitalizations occur yearly in Argentina, Chile and
      Venezuela, respectively.

PMID- 11465842
TI  - Rotavirus in Ireland: national estimates of disease burden, 1997 to 1998.
AB  - BACKGROUND: We estimated the disease burden caused by rotavirus hospitalizations
      in the Republic of Ireland by using national data on the number of
      hospitalizations for diarrhea in children and laboratory surveillance of
      confirmed rotavirus detections. METHODS: We examined trends in diarrheal
      hospitalizations among children <5 years old as coded by ICD-9-CM for the period
      January, 1997, to December, 1998. We collated data on laboratory-confirmed
      rotavirus detections nationally for the same period among children <2 years old.
      We calculated the overall contribution of rotavirus to laboratory-confirmed
      intestinal disease in children <5 years old from INFOSCAN, a disease bulletin for
      one-third of the population. We compared data from all sources and estimated the
      proportion of diarrheal hospitalizations that are likely the result of rotavirus
      in children <5 years old. RESULTS: In children <5 years old, 9% of all
      hospitalizations are for diarrheal illness. In this age group 1 in 8 are
      hospitalized for a diarrheal illness, and 1 in 17 are hospitalized for rotavirus
      by 5 years of age. In hospitalized children <2 years old, 1 in 38 have a
      laboratory confirmed rotavirus infection. CONCLUSIONS: The disease burden of
      rotavirus hospitalizations is higher than in other industrialized countries.
      Access to comprehensive national databases may have contributed to the high
      hospitalization rates, as well as a greater tendency to hospitalize children with
      diarrhea in Ireland.

PMID- 11465843
TI  - Erythrocyte sedimentation rate and C-reactive protein discrepancy and high
      prevalence of coronary artery abnormalities in Kawasaki disease.
AB  - BACKGROUND: An outbreak of Kawasaki disease (KD) in Colorado between November,
      1997, and June, 1998, provided the opportunity to study inflammatory indices and
      coronary artery abnormalities. METHODS: Medical records of the 33 patients
      diagnosed with KD at The Children's Hospital during the outbreak were reviewed.
      Demographic and clinical information, C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR) and echocardiogram results were recorded. Traditional
      abnormalities (dilatation, aneurysm, ectasia), as well as "prominence" of the
      coronary arteries were noted. RESULTS: Twenty-five patients had CRP and ESR
      performed on the day of admission; 11 of 25 (44%) had a discrepancy between the
      height of the ESR and CRP values (high ESR and low CRP or low ESR and high CRP).
      The mean CRP was higher in patients who presented in <10 days than in patients
      who presented in > or =10 days: 13.9 mg/dl vs. 5.2 mg/dl (P = 0.01). The ESR
      value did not correlate with the day of illness. Age, gender or presence of
      coronary artery abnormalities did not correlate with the height of CRP or ESR
      elevation. Thirty percent of patients had at least one abnormality on their
      initial echocardiogram (dilatation, aneurysm, ectasia). An additional 24% of
      patients displayed prominence as the only finding on their initial
      echocardiogram. Of the 33 patients 7 (21.2%) had coronary artery aneurysms.
      CONCLUSIONS: Many patients with KD have discrepancies in the degree of elevation
      of CRP and ESR. Physicians should consider obtaining both tests in patients with
      KD. This outbreak was associated with a high degree of coronary artery
      abnormalities. The finding of coronary artery prominence is an observation that
      deserves further study.

PMID- 11465844
TI  - Lack of association between Kawasaki syndrome and infection with Rickettsia
      conorii, Rickettsia typhi, Coxiella burnetii or Ehrlichia phagocytophila group.
AB  - BACKGROUND: The etiology of Kawasaki syndrome (KS) is unknown. Rickettsiae,
      intracellular microorganisms that invade the vascular endothelium, might cause
      KS. OBJECTIVES: To investigate whether there is an association between KS and
      infection with Rickettsia conorii, Rickettsia typhi, Coxiella burnetii or
      Ehrlichia phagocytophila group. METHODS: All children who were diagnosed with KS
      at the University of Athens Second Department of Pediatrics from December, 1999,
      through November, 2000, were prospectively studied. Paired serum specimens were
      obtained from all patients and antibody titers against R. conorii, R. typhi, C.
      burnetii and E. phagocytophila group were assessed by microimmunofluorescence
      assay. RESULTS: Eleven children with a median age of 2.5 years were included in
      the study. A 15-month-old child had a 4-fold rise of antibody titers against C.
      burnetii, which is indicative of acute Q fever. The patient had a history of
      recent exposure to possible sources of C. burnetii. The remaining patients tested
      negative for the presence of antibodies against R. conorii, R. typhi, C. burnetii
      and E. phagocytophila group. CONCLUSIONS: Our study does not provide serologic
      evidence that KS is the result of infection with R. conorii, R. typhi, C.
      burnetii or E. phagocytophila group. It is suggested that C. burnetii may cause a
      KS-like illness in young children.

PMID- 11465845
TI  - Infant botulism.

PMID- 11465846
TI  - Patient care guidelines and pediatric infectious diseases.

PMID- 11465847
TI  - Nocardiosis in South Texas children.
AB  - Primary cutaneous nocardiosis can present as cellulitis or abscess with or
      without lymphadenitis. In South Texas children with suspected Staphylococcus
      aureus or Streptococcus pyogenes skin and soft tissue infections who do not
      improve as expected with appropriate antibiotics, physicians should consider
      Nocardia brasiliensis in the differential diagnosis, especially if there are
      multiple lesions in a lymphocutaneous distribution.

PMID- 11465848
TI  - Timing and interpretation of tests for diagnosing perinatally acquired hepatitis
      C virus infection.
AB  - The diagnosis of hepatitis C virus (HCV) infection in children born to HCV
      infected women is based on serologic assays and HCV RNA measurement by PCR.
      Interpretation of the results of these tests is hampered by uncertainty about the
      age distribution of loss of maternal antibody and the sensitivity and specificity
      of PCR at different ages. On the basis of findings from a recent vertical
      transmission study, we estimated the posttest probability of a child's being
      infected or uninfected under several test result scenarios. These estimates may
      assist clinicians in assessing the likelihood of infection in an individual child
      and in using the currently available assays cost effectively.

PMID- 11465849
TI  - Short course directly observed therapy to monitor compliance with antiretroviral
      therapy in human immunodeficiency virus-infected children.
AB  - We report our experience with short course directly observed therapy (DOT) in six
      human immunodeficiency virus-infected children who had a poor response to their
      prescribed therapy. Four to 8 days of DOT resulted in a significant drop in the
      viral load of all six children, demonstrating that short course DOT is an
      effective way to document poor compliance with antiretroviral therapy.

PMID- 11465850
TI  - Evaluation of Binax now Streptococcus pneumoniae urinary antigen test in children
      in a community with a high carriage rate of pneumococcus.
AB  - Pneumococcal antigen was present in urine from 49 of 102 well Gambian children.
      Eighty-nine of the 102 were nasopharyngeal carriers of pneumococci. The positive
      predictive value for carriage was 96%, and the negative predictive value was 22%.
      The test is not useful for predicting etiology of disease in populations with a
      high rate of nasopharyngeal carriage of pneumococci.

PMID- 11465851
TI  - Bone marrow failure with concurrent enteroviral infection in a newborn.
AB  - A newborn baby, with transient pancytopenia concurrent to Echovirus type 11
      infection, was hospitalized for fever, diarrhea, rash, generalized petechiae and
      hepatosplenomegaly. Subsequent investigation showed bone marrow failure. To our
      knowledge this is the first reported case of bone marrow failure with concomitant
      enteroviral infection.

PMID- 11465852
TI  - Cholestasis as a presenting feature of acute Epstein-Barr virus infection.
AB  - Biochemical evidence of hepatic involvement in Epstein-Barr virus disease is
      common but clinical features of cholestasis are rare in children. We present
      three children with cholestasis as a presenting feature of Epstein-Barr virus
      disease.

PMID- 11465853
TI  - Chlamydia trachomatis disguised as an asymptomatic scrotal mass in adolescents.
AB  - We present two cases of adolescents who presented with painless scrotal masses
      suggestive of testicular cancer. Diagnostic workup of both these patients
      revealed Chlamydia trachomatis and both patients were successfully treated with
      doxycycline. Both patients initially denied sexual activity. We suggest that a
      high index of suspicion is warranted in adolescent patients that present with
      asymptomatic scrotal masses and precise tests for C. trachomatis be done to rule
      out an infectious cause.

PMID- 11465854
TI  - Irritability and neck stiffness in a five-month-old infant.

PMID- 11465855
TI  - Experience during the first fifteen months of New York State expedited human
      immunodeficiency virus testing.

PMID- 11465856
TI  - Do viridans streptococci cause pneumonia in children?

PMID- 11465857
TI  - Fast intracellular motion in the living cell by video rate reflection confocal
      laser scanning microscopy.
AB  - Fast intracellular motion (FIM) was first revealed by back scattered light (BSL)
      imaging in video rate confocal scanning laser microscopy (VRCSLM), beyond the
      limits of spatial and temporal resolution obtainable with conventional optical
      microscopy. BSL imaging enabled visualisation of intra and extracellular motion
      with resolution in space down to 0.2 microm and in time to 1/25th of a second.
      Mapping the cell space at 0.2 microm x 0.2 microm (XY = in instantaneous best
      focal plane) x 0.5 microm (Z = height/depth, optic axis direction) volume steps
      revealed a communication layer above the known contact layer and an integrated
      dynamic spatial network (IDSN) towards the cell centre. FIM was originally
      observed as localised quasichaotic dancing (dithering) or reflecting
      patches/spots in the cell centre, faster in the darker nuclear space. Later, a
      second type of FIM was recognised which differed by the presence of a varied
      proportion of centrifugal and centripetal directional movements and/or jumping of
      patches/spots in the cell centre and outside the nuclear space. The first type is
      characteristic for cells in slightly adverse conditions while the second type has
      so far only been found in eutrophic cells. Temporal speeding up and coarsening of
      FIM, followed by slowing and eventually cessation at cell death, was found on
      exposure to strong stressors. It was concluded that the state of FIM provides
      instantaneous information about individual cell reactions to actual treatment and
      about cell survival. A putative switch between the first and second type FIM
      could be considered as an indicator of timing of cellular processes. The
      significance of FIM for the biology of the cell is seen in the rapid assessment
      of the condition of an individual live cell investigated by combination of
      various methods. Requirements for further development of this approach are
      outlined.

PMID- 11465858
TI  - Growth promoting effects of human placental lactogen during early organogenesis:
      a link to insulin-like growth factors.
AB  - Many maternally derived factors may be involved in the regulation of embryonic
      growth but the control mechanisms involved are poorly understood. Human placental
      lactogen (hPL) has been implicated in playing a role in the control of embryonic
      growth. Several investigators suggested that there may be a possible link between
      the effects of this hormone and insulin-like growth factors (IGFs). In order to
      determine the growth promoting potential of hPL and involvement of IGFs in the
      mechanism of action of the hormone, 9.5 d rat embryos were cultured in vitro for
      48 h in depleted serum in the presence and absence of hPL with additional IGF
      antisera. The growth supporting capacity of the serum was reduced by removal of
      low molecular weight molecules by prolonged filtration of the serum using filters
      with a molecular weight exclusion of 30 kDa. Addition of hPL (3.2-25.6 ng/ml) to
      depleted serum significantly improved embryonic growth and development,
      suggesting that the developing embryo may utilise hPL. The presence of antisera
      against hPL, IGF-I and -II abolished the hPL-induced increase in the development
      in all parameters suggesting that there may be a possible link between the IGFs
      and the effects of hPL on rat embryonic development and this hormone may achieve
      its growth promoting effects via IGFs.

PMID- 11465859
TI  - Immunolocalisation of neuronal nitric oxide synthase at the neuromuscular
      junction of MDX mice: a confocal microscopy study.
AB  - The distribution of nitric oxide synthase at the neuromuscular junction (NMJ) of
      normal, denervated and mdx mice was studied using a specific antibody against the
      neuronal isoform of nitric oxide synthase (nNOS). Fluorescence confocal
      microscopy demonstrated that nNOS immunoreactivity was localised mainly in the
      sarcolemma and presynaptic region covering acetylcholine receptor branches. The
      expression of presynaptic nNOS was greatly reduced in dystrophin-deficient
      muscles. In normal denervated muscles, nNOS was still present in the presynaptic
      region and there were no qualitative changes in the expression of this protein.
      These results suggest that the presynaptic distribution of nNOS is associated
      with terminal Schwann cells. The relationship between nNOS and the presynaptic
      components of the neuromuscular junction may open new perspectives for improving
      our understanding of the pathogenesis of dystrophic muscles.

PMID- 11465860
TI  - Glycan composition of follicle (Sertoli) cells of the amphibian Pleurodeles
      waltl. A lectin histochemical study.
AB  - The glycan composition of the N- and O-linked oligosaccharides of the follicle
      (Sertoli) cells of the urodele amphibian Pleurodeles waltl testis were identified
      by lectin histochemistry, performed alone or in combination with enzymatic and
      chemical deglycosylation methods. The follicle cells were shown to contain: (1)
      Fuc, Galbeta(1,4)GlcNAc, GalNAc and Neu5Acalpha(2,3)Galbeta(1,4)GlcNAc in both N-
      and O-linked oligosaccharides; (2) Man in N-linked glycans; and (3)
      Galbeta(1,3)GalNAc in O-linked sugar chains. The follicle cells at the pre- and
      postmeiotic stages showed some differences in the UEA-1-positive Fuc
      characterisation, suggesting differences in the glycan composition. In addition,
      the sequence Neu5Acalpha(2,6)Gal/GalNAc was shown in the follicle cells only
      after spermiation, in the sperm-empty lobules of the developing glandular tissue.
      These results suggest that the follicle cells modify their glycoprotein content,
      probably for the performance of new roles, as the spermatogenetic cells develop.
      Thus the follicle cells surrounding male germ cells at different spermatogenetic
      stages would contain different glycoproteins involved in specific roles during
      male germ cell proliferation and maturation.

PMID- 11465861
TI  - Morphological diversity in digital skin microstructure of didelphid marsupials.
AB  - The purpose of this study was to investigate how didelphid marsupials have
      diversified in morphology of their claws and digital pads as they evolved
      different foraging preferences such as terrestrial, aquatic, and arboreal feeding
      behaviours. Both arboreal and more terrestrial didelphids have papillary ridges
      on the digital pads of the fore and hindfoot. In contrast, the papillary ridges
      on the pedal digital skin of the water opossum Chironectes minimus have been
      replaced by nonoverlapping, thickened epidermal scales. Chironectes also differs
      from the other didelphids studied in having finger tips with reduced claws and
      digital pads that are covered with raised epidermal scales having projecting,
      finger-like cones arranged radially around the perimeter of each scale. The
      reduced claws and unusual digit skin microstructure of Chironectes likely improve
      this animal's ability to recognise and identify live animal prey under water
      using only its sense of touch.

PMID- 11465862
TI  - Frequency variations of discrete cranial traits in major human populations. I.
      Supernumerary ossicle variations.
AB  - Four supernumerary ossicle variations-the ossicle at the lambda, the parietal
      notch bone, the asterionic bone, and the occipitomastoid bone-were examined for
      laterality differences, intertrait correlations, sex differences, and between
      group variations in the samples from around the world. Significant laterality
      differences were not detected in almost all samples. In some pairs of traits,
      significant association of occurrence were found. Several geographic samples were
      sexually dimorphic with respect to the asterionic bone and to a lesser extent for
      the parietal notch bone. East/Northeast Asians including the Arctic populations
      in general had lower frequencies of the 4 accessory ossicles. Australians,
      Melanesians and the majority of the New World peoples, on the other hand,
      generally had high frequencies. In the western hemisphere of the Old World,
      Subsaharan Africans had relatively high frequencies. Except for the ossicle at
      the lambda, the distribution pattern in incidence showed clinal variation from
      south to north. Any identifiable adaptive value related to environmental or
      subsistence factors may be expressed in such clinal variation. This may allow us
      to hypothesise that not only mechanical factors but a founder effect, genetic
      drift, and population structure could have been the underlying causes for
      interregional variation and possible clines in the incidences of the accessory
      ossicles.

PMID- 11465863
TI  - Frequency variations of discrete cranial traits in major human populations. II.
      Hypostotic variations.
AB  - Five discrete hypostotic cranial traits, tympanic dehiscence, ovale-spinosum
      confluence, metopism, transverse zygomatic suture vestige, and biasterionic
      suture, were investigated in 81 human population samples. Except for ovale
      spinosum confluence, marked asymmetric occurrences of the bilateral traits were
      not detected in the majority of the samples. Significant intertrait association
      was observed mainly between the biasterionic suture and other sutural variations
      including accessory ossicles. The traits showing relatively consistent sex
      differences across diverse populations were tympanic dehiscence, which is
      predominant in females, and biasterionic suture in males. On a world scale, the 5
      hypostotic cranial traits showed distinctive patterns of geographical variation.
      Different clinal variations within and between macrogeographical areas such as
      western and eastern parts of the Old World were found for the frequencies of the
      traits. The Ainu may be the most distinct outlier in the eastern Asian region on
      the basis of the incidence of the traits, especially the transverse zygomatic
      suture vestige. The interregional variation without reasonable adaptive value and
      nonadaptive shift of the possible outliers presented in this study suggest that
      the genetic background for the occurrence of these traits cannot be excluded
      completely.

PMID- 11465864
TI  - Age-related changes in rat cerebellar basket cells: a quantitative study using
      unbiased stereological methods.
AB  - Cortical cerebellar basket cells are stable postmitotic cells; hence, they are
      liable to endure age-related changes. Since the cerebellum is a vital organ for
      the postural control, equilibrium and motor coordination, we aimed to determine
      the quantitative morphological changes in those interneurons with the ageing
      process, using unbiased techniques. Material from the cerebellar cortex (Crus I
      and Crus II) was collected from female rats aged 2, 6, 9, 12, 15, 18, 21 and 24
      mo (5 animals per each age group), fixed by intracardiac perfusion, and processed
      for transmission electron microscopy, using conventional techniques. Serial
      semithin sections were obtained (5 blocks from each rat), enabling the
      determination of the number-weighted mean nuclear volume (by the nucleator
      method). On ultrathin sections, 25 cell profiles from each animal were
      photographed. The volume density of the nucleus, ground substance, mitochondria,
      Golgi apparatus (Golgi) and dense bodies (DB), and the mean surface density of
      the rough endoplasmic reticulum (RER) were determined, by point counting, using a
      morphometric grid. The mean total volumes of the soma and organelles and the mean
      total surface area of the RER [SN (RER)] were then calculated. The results were
      analysed with 1-way ANOVA; posthoc pairwise comparisons of group means were
      performed using the Newman-Keuls test. The relation between age and each of the
      parameters was studied by regression analysis. Significant age-related changes
      were observed for the mean volumes of the soma, ground substance, Golgi, DB, and
      SN (RER). Positive linear trends were found for the mean volumes of the ground
      substance, Golgi, and DB; a negative linear trend was found for the SN (RER).
      These results indicate that rat cerebellar basket cells endure important age
      related changes. The significant decrease in the SN (RER) may be responsible for
      a reduction in the rate of protein synthesis. Additionally, it may be implicated
      in a cascade of events leading to cell damage due to the excitotoxic activity of
      glutamate, which could interfere in the functioning of the complex cerebellar
      neuronal network.

PMID- 11465865
TI  - Biometric study of the relationships between palmar neurovascular structures, the
      flexor retinaculum and the distal wrist crease.
AB  - During surgical exposure of the carpal tunnel it is possible to injure the
      neurovascular structures closely related to the flexor retinaculum, such as the
      superficial palmar arch and the communicating branch between the ulnar and median
      nerves. Because of the importance of these structures and with the purpose of
      increasing knowledge of anatomical details concerning to their location, a
      biometric study was performed on the retinaculum and the communicating branch,
      and between the communicating branch and the distal wrist crease, as well as
      between the retinaculum and the superficial palmar arch. We dissected 56 hands
      from 28 Brazilian formalin-preserved cadavers of both sexes (24 male) at the
      Federal University of Sao Paulo-Escola Paulista de Medicina, Brazil. The
      communicating branch was observed in 96.4% of cases and the superficial palmar
      arch in 78.6%. The communicating branch was found between the common palmar
      digital nerve of the 4th interosseous space (from the ulnar nerve) to the
      homonymous nerve of the 3rd interosseous space (from the median nerve). In males,
      the distance between the distal wrist crease and the site where the communicating
      branch originates from the ulnar component had an average of 33.9 +/- 5.5 mm on
      the right side and 30.2 +/- 8.2 mm on the left. The distance between the distal
      wrist crease and the junction of the communicating branch with the common palmar
      digital nerve of the 3rd interosseous space was 43.6 +/- 6.9 mm on the right and
      40.2 +/- 6.2 mm on the left side. Conversely, in 14.8% of cases (1 female), the
      communicating branch was observed to emerge from the common palmar digital nerve
      of the 3rd interosseous space. The distance between the retinaculum and the
      superficial palmar arch in the axial line of the 4th metacarpal bone was on
      average 7.3 +/- 4.3 mm on the right and 8.3 +/- 3.5 mm on the left side. At the
      same level, the distance between the retinaculum and the communicating branch was
      6.2 +/- 3.7 mm on the right side and 5.1 +/- 2.8 mm on the left. These results
      can be used as a reference during surgical procedures in the palmar region.

PMID- 11465866
TI  - The acetabular point: a morphological and ontogenetic study.
AB  - The acetabular point was analysed by studying human pelvic bones from 326
      individuals ranging from newborns to age 97 y. The bones were categorised into 3
      groups according to the degree of fusion for the 3 elements of the pelvis:
      nonfused (59), semifused (5) and fused (262). The acetabular point in immature
      pelvic bones is clearly represented by the point of the fusion lines for each
      bony element at the level of the acetabular fossa. In adult pelvic bones the
      acetabular fossa has an irregular clover-leaf shape, the superior lobe being
      smaller than the anterior and posterior lobes. Cross-sectional analysis of
      acetabular morphology suggested that the acetabular point in adult pelvic bones
      is always represented by the indentation between the superior and the anterior
      lobes of the acetabular fossa.

PMID- 11465867
TI  - Anti-Smoking therapies: is harm reduction a viable alternative to smoking
      cessation?
AB  - Smoking cessation should be proposed to all smokers by healthcare workers;
      however, severely dependent smokers are frequently unable or unwilling to quit
      smoking. For some of them, particularly if they have failed in previous cessation
      attempts and have smoking-related disorders, a long term reduction of tobacco
      consumption may be proposed as the 'second best' attitude and may offer a
      perspective for reduction of some of the risk factors associated with smoking.
      This attitude, which cannot be regarded as a general health policy, usually
      requires the prolonged use of nicotine replacement therapy. From available
      studies, it does not seem that a period of sustained smoking reduction decreases
      the chance of future cessation, it may even increase it.

PMID- 11465868
TI  - Antiepileptogenic agents: how close are we?
AB  - Epilepsy is a common neurological condition, affecting about 4% of individuals
      over their lifetime. Epilepsy can be idiopathic, secondary to an underlying
      genetic abnormality or unknown causes, or acquired. Known potential causes
      account for about one third of epilepsy. Control of epilepsy has primarily
      focused on suppressing seizure activity after epilepsy has developed. An
      intriguing possibility is to control acquired epilepsy by preventing
      epileptogenesis, the process by which the brain becomes epileptic. Many
      laboratory models simulate human epilepsy as well as provide a system for
      studying epileptogenesis. The kindling model involves repeated application of
      subconvulsive electrical stimulation to the brain, leading to spontaneous
      seizures. Other models include the cortical or systemic injection of various
      chemicals. These models suggest that many antiepileptic drugs, from phenobarbital
      and valproate (valproic acid) to levetiracetam and tiagabine, have
      antiepileptogenic potential. Some promising other possibilities include N-methyl
      D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA) antagonists as well as the neurotrophins and their receptors.
      Phenobarbital, phenytoin, valproate, carbamazepine and, to a very limited extent,
      diazepam have been evaluated in clinical trials to test whether they actually
      prevent epileptogenesis in humans. Results have been very disappointing. Meta
      analyses of 12 different drug-condition combinations show none with significantly
      lower unprovoked seizure rates among those receiving the active drug. In 4 of the
      12, the observed rate was actually slightly higher among treated individuals.
      None of the newer drugs have been evaluated in antiepileptogenesis trials. Until
      some drugs demonstrate a clear antiepileptogenic effect in clinical trials, the
      best course to reduce the incidence of epilepsy is primary prevention of the risk
      increasing events--for example, wearing helmets, using seat belts, or decreasing
      the risk of stroke by reducing smoking.

PMID- 11465869
TI  - Intraperitoneal drug delivery of antineoplastics.
AB  - The administration of antineoplastic agents directly into the peritoneal cavity
      as treatment of localised cancer is based on sound pharmacokinetic principles.
      This unique technique has to the potential to optimise outcome in settings where
      preclinical and clinical data suggest that cytotoxicity of a specific drug
      against a particular tumour type is enhanced by either increasing the drug
      concentration or duration of exposure. Phase I trials have confirmed the safety
      and pharmacokinetic advantage for a number of agents delivered by the
      intraperitoneal relative to the systemic route, including cisplatin (10- to 20
      fold advantage for regional delivery), carboplatin (10- to 20-fold advantage),
      and paclitaxel (1,000-fold advantage). In phase II trials, performed mostly in
      patients with ovarian cancer, this approach has achieved objective responses in
      settings where intravenous drug delivery has not achieved the desired effect
      (e.g. surgically documented complete response using intraperitoneal cisplatin as
      second-line therapy of ovarian cancer). Phase III trials employing
      intraperitoneal cisplatin as initial treatment of small volume advanced ovarian
      cancer have demonstrated that regional therapy results in a modest, but
      statistically significant, improvement in both progression-free and overall
      survival compared to intravenous cisplatin. Further exploration of this novel
      method of treatment, including the conduct of definitive randomised phase III
      clinical trials, is indicated in ovarian cancer and in other tumour types where
      clinical manifestations are principally localised to the peritoneal cavity.

PMID- 11465870
TI  - Pharmacotherapy of ectoparasitic infections.
AB  - Epizoonoses such as scabies, lice and cimicosis are common, vexing disorders that
      occur worldwide. Historically, many treatment modalities have been employed in
      the management of these disorders, and most of the drugs described in this review
      are of historical interest and no longer recommended or in widespread use because
      of their wide spectrum of adverse effects. More recently, reports documenting
      resistance against various antiectoparasite drugs, complicated and severe courses
      of the diseases, and adverse effects of drug therapy have prompted the
      development of new treatment strategies and drugs for optimal disease management.
      Because the strategies currently recommended for the treatment of ectoparasites
      differ worldwide, this review proposes a rational approach to selecting the best
      therapeutic agent by comparing the pharmacokinetics, pharmacodynamics, drug
      efficacy and adverse effects. A literature search of the currently Internet
      accessible libraries PubMed, Medline and Ideal library, of citations of articles
      found there, and from communications with the Federal Institute for Drugs and
      Medical Devices, Germany, was conducted based on this approach. One major
      observation of this literature search is that permethrin is the treatment of
      choice for lice and scabies in the US and in Great Britain, whereas lindane is
      still recommended for scabies in most other European countries because of its
      longer-standing record of effectiveness. Although permethrin has not yet been
      proven to be more effective than lindane in treating infections with these
      ectoparasites, it currently appears to have the best efficacy versus safety
      profile of topical treatments for scabies and lice. Ivermectin is a newer oral
      drug for the treatment of ectoparasites, which has been used with great success
      in the treatment of onchocercosis and other endoparasites. Although ivermectin
      appears to be a promising drug, its role in the treatment of ectoparasitic
      infections will be clarified as more study data become available. Finally, it is
      important to emphasise the clinical aspects of ectoparasite therapy and that
      providing the patient with optimal instructions on the use of topical
      therapeutics is of great importance in avoiding adverse effects and assuring
      complete removal of the ectoparasite, thereby avoiding the development of drug
      resistance.

PMID- 11465871
TI  - Meniere's disease: pathophysiology and treatment.
AB  - Meniere's disease is defined by the association of 4 symptoms: vertigo attacks,
      fluctuating hearing loss, tinnitus and an auricular plenitude sensation. The
      pathophysiology is commonly explained by a distension of membranous labyrinth by
      the endolymph, equally called endolymphatic hydrops. Recent studies also tend to
      relate the disease to immune mechanisms. The treatment is medical in the majority
      of patients but there is no international consensus on the management of the
      different stages of Meniere's disease. Regarding the lack of clinical studies
      clearly demonstrating the effectiveness of a certain therapy or another. the
      recommendations are usually based on the empirical experience of practitioners
      and on the observation of a marked amelioration at 2 years of treatment in the
      majority of patients. The treatment of the acute phase of Meniere's disease is
      basically symptomatic. Vestibular suppressant drugs have a well-established
      record in controlling acute attacks of vertigo. Most have variable
      anticholinergic, anti-emetic and vestibular sedative effects. If necessary, the
      administration of benzodiazepines will help to alleviate anxiety. Long term
      management of Meniere's disease includes a low salt diet, the use of diuretics in
      the post-crisis phase, and the very common use in Europe of histaminergic agents.
      Corticosteroids are used in bilateral forms of Meniere's disease, particularly if
      an autoimmune basis is suspected. All authors insist on the interest and the
      importance of regular follow-up, especially with regard to the psychological
      status and responsiveness to treatment of the patient. Surgical indications are
      rare and the least invasive procedures are used first. The choice of the
      procedure should take into consideration the need to preserve the auditory
      function of the patient.

PMID- 11465872
TI  - Pursuit of optimum outcomes in ovarian cancer: methodological approaches to
      therapy.
AB  - The treatment of ovarian cancer is an evolving area and important clinical
      questions remain unanswered at all stages from early disease to relapse. This
      review outlines current practice at each disease stage, some of the current
      unanswered questions and issues surrounding the design of clinical trials to
      answer these questions. The gold standard test for new treatments must remain the
      randomised controlled trial with survival as the major endpoint because other
      outcome measures such as radiological response do not bear a strong relationship
      to survival. Patient factors greatly influence the likelihood of response to
      treatment and subsequent survival, hence failure to control for these in trial
      design may lead to spurious results. Quality of life is an important endpoint but
      quality-of-life measures in clinical trials should be interpreted carefully. The
      introduction of novel, target directed anticancer therapies will require new
      study designs as the phase I/II/III paradigm may not be relevant. It is current
      practice to offer adjuvant chemotherapy to women with early stage disease who are
      considered at high risk of relapse despite conflicting evidence from clinical
      trials. Current questions include the optimal choice of regimen and the duration
      of treatment. However, the relative rarity of early stage disease and the likely
      small difference between treatments makes evaluations difficult. Advanced disease
      is currently treated using a combination of surgical cytoreduction and platinum
      paclitaxel chemotherapy. Women with poor risk disease are unlikely to be cured of
      their disease and the investigation of strategies to minimise treatment may be
      appropriate. Conversely, women with good risk disease may be better candidates
      for experimental treatment to increase cure rate. Strategies that have been tried
      include dose-intensification, high-dose therapy and intraperitoneal therapy.
      Whereas there is some evidence to support the latter, there is no current
      evidence for dose-intensification or high-dose therapy, and these must remain
      areas of investigation. Most current trials investigate the addition of agents to
      platinum-paclitaxel. Relapsed disease is an important area. Despite this, only 9
      randomised controlled trials have been undertaken. Uncertainties exist in the
      role of surgery, both surgical cytoreduction and palliative surgery. The mainstay
      of treatment at disease relapse is chemotherapy and the choice of agent revolves
      around the concept of platinum sensitivity. Many agents are active in platinum
      resistant disease, but uncertainties remain about the relative efficacies of each
      and the place of combination therapy.

PMID- 11465873
TI  - Caspofungin.
AB  - Caspofungin is the first in a new class of antifungal agents, the glucan
      synthesis inhibitors, that interfere with fungal cell wall synthesis. Caspofungin
      exhibited in vitro and in vivo efficacy against a wide range of fungi and yeasts
      including Aspergillus and Candida species. A complete or partial response to
      caspofungin therapy was seen in 40.7% of immunocompromised adults with invasive
      aspergillosis who did not respond to, or did not tolerate, other antifungal
      agents in a noncomparative multicentre study. Caspofungin was effective in
      patients with oropharyngeal or oesophageal candidiasis, according to the
      preliminary results of 2 randomised double-blind trials. Caspofungin was
      generally well tolerated in a multicentre noncomparative trial involving patients
      with invasive aspergillosis. One or more drug-related clinical adverse effects
      were experienced by 13.8% of caspofungin recipients (the most common were fever,
      nausea, vomiting and complications associated with the vein into which
      caspofungin was infused). The tolerability of caspofungin appeared to be better
      than that of amphotericin B and similar to that of fluconazole in double-blind,
      randomised trials involving patients with mucosal candidiasis.

PMID- 11465874
TI  - Parecoxib (parecoxib sodium).
AB  - Parecoxib (parecoxib sodium) is an injectable pro drug of valdecoxib, which is a
      potent and selective inhibitor of cyclo-oxygenase-2. Intravenous (IV) or
      intramuscular (IM) parecoxib >20 mg has analgesic activity superior to that of
      placebo and similar to that of IV or IM ketorolac 30 or 60 mg well controlled
      trials in patients with postoperative dental pain (n = 304 to 457). In a well
      controlled trial (n = 202), IV parecoxib 20 or 40mg showed analgesic activity
      greater than that of placebo and IV morphine 4mg and similar to that of IV
      ketorolac 30 mg following gynaecological surgery Following orthopaedic surgery,
      the analgesic activity of IV parecoxib 20 or 40mg was similar to that of IV
      ketorolac 30 mg and superior to that of IV morphine 4 mg or placebo in well
      controlled trials (n = 175 and 208). IV parecoxib (40 mg twice daily for 7 days)
      produced significantly fewer gastrointestinal erosions and/or ulcers than
      ketorolac (15 mg 4 times a day for 5 days) in healthy volunteers in a well
      controlled trial; effects on upper gastrointestinal mucosa were similar for
      parecoxib and placebo. Parecoxib is well tolerated after dental, gynaecological
      or orthopaedic surgery. The most common adverse events irrespective of treatment
      (parecoxib, ketorolac or placebo) after dental surgery were nausea, alveolar
      osteitis, dizziness and headache. Nausea, abdominal pain, headache, abdominal
      fullness, dizziness, back pain, fever, hypoactive bowel sounds, vomiting,
      tachycardia, somnolence, abnor mal breath sounds and pruritus occurred in > or =
      10% of parecoxib recipients after gynaecological surgery. Similar results were
      seen in placebo recipients.

PMID- 11465875
TI  - Valganciclovir.
AB  - Valganciclovir is a prodrug of ganciclovir which has been developed for the
      treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral
      valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral
      bioavailability of ganciclovir after oral valganciclovir administration is high.
      Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to
      that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study
      indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg
      once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5
      mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV
      retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar
      tolerability profile to intravenous ganciclovir during induction therapy in
      patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy
      with valganciclovir, the most commonly reported adverse events included
      neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea,
      nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral
      neuropathy, paraesthesia and retinal detachment.

PMID- 11465876
TI  - Ganciclovir: an update of its use in the prevention of cytomegalovirus infection
      and disease in transplant recipients.
AB  - Ganciclovir is a nucleoside guanosine analogue which incorporates ganciclovir
      triphosphate (the active moiety) into DNA during elongation, thereby inhibiting
      viral replication. Comparative studies of pre-emptive and prophylactic
      ganciclovir therapies in bone marrow transplant (BMT) recipients have shown
      similar rates of cytomegalovirus (CMV) infection, disease and patient mortality.
      Long term prophylaxis with either oral, or sequential intravenous/oral,
      ganciclovir has shown efficacy in renal allograft recipients, including high risk
      patients or those receiving antilymphocyte antibody therapy. A preliminary study
      indicates that ganciclovir is more efficacious than aciclovir in paediatric
      patients. Both oral and intravenous prophylactic ganciclovir regimens have shown
      efficacy compared with no antiviral treatment in lung transplant recipients;
      initial reports have shown similar efficacy between pre-emptive and prophylactic
      ganciclovir. Oral ganciclovir monotherapy is as efficacious as sequential
      intravenous/oral ganciclovir therapy in liver transplant recipients. Pre-emptive
      treatment was equally as effective as long term ganciclovir prophylaxis in high
      risk patients. Ganciclovir prophylaxis for 4 weeks appears ineffective in heart
      allograft recipients treated with antithymocyte globulin. Long term sequential
      intravenous/ oral ganciclovir therapy has shown greater efficacy in preventing
      CMV disease than sequential ganciclovir/aciclovir therapy. in these patients.
      Initial reports indicate that pre-emptive therapy may be beneficial in this
      patient group. although this remains to be determined. Ganciclovir in therapeutic
      dosage regimens generally has acceptable tolerability with adverse effects
      usually of a haematological or neurological nature. Neutropenia, thrombocytopenia
      and anaemia are the primary dose-limiting toxicities associated with ganciclovir
      therapy. Overall, neutropenia occurs less frequently with administration of oral
      ganciclovir than with intravenous ganciclovir. Monitoring of renal function is
      recommended as serum creatinine levels may rise during ganciclovir therapy. In
      addition, ganciclovir prophylaxis appears more cost effective than the majority
      of other currently available therapies for CMV with oral ganciclovir more cost
      effective than intravenous ganciclovir. In conclusion, it is unlikely that a
      single strategy will be able to be applied to all transplant patients for the
      prevention of CMV disease. An optimal strategy will probably be arisk-adapted
      approach. Prophylactic treatment with ganciclovir appears the best strategy to
      implement in high risk patients: oral ganciclovir formulations may be best
      employed where lower toxicity is required. Pre-emptive treatment with ganciclovir
      appears most efficacious in patients identified as lower risk or, in the case of
      BMT recipients, where lower toxicity may be desirable. Ganciclovir remains an
      important therapeutic option for the prevention and treatment of CMV disease in
      transplant recipients.

PMID- 11465877
TI  - Reviparin: a review of its efficacy in the prevention and treatment of venous
      thromboembolism.
AB  - Reviparin (reviparin sodium) is a low molecular weight heparin (LMWH) that
      catalyses the inactivation of factors Xa and IIa by binding to antithrombin,
      which ultimately leads to the inhibition of the clotting cascade. It is
      administered subcutaneously. Reviparin 7,000 to 12,600 anti-XaIU/day was found to
      be as effective as intravenous unfractionated heparin in preventing the clinical
      recurrence of acute deep vein thrombosis (DVT) and/or pulmonary embolism in 1
      large randomised, multicentre trial (COLUMBUS) and was significantly more
      effective than intravenous unfractionated heparin in the prevention of recurrent
      venous thromboembolism in another large randomised, multicentre trial (CORTES).
      Reviparin has also been compared with unfractionated heparin in children with
      established DVT. However, the trial was under-powered and no conclusion could be
      made regarding comparative efficacy. As prophylaxis, reviparin 1,750 anti-XaIU
      once daily was as effective as unfractionated heparin 5,000IU twice daily in
      1,311 patients undergoing abdominal surgery and, in a once daily dosage of 4,200
      anti-XaIU, was as effective as subcutaneous enoxaparin sodium 40 mg/day or
      acenocoumarol in patients undergoing hip replacement surgery. Reviparin 1,750
      anti-XaIU also effectively prevented DVT. compared with no treatment, in patients
      undergoing knee arthroscopy. It was also more effective than placebo in patients
      with brace immobilisation of the lower extremity. Reviparin was compared with
      'standard care' in children with central venous lines. However, the trial was too
      small to make conclusions regarding its efficacy. Comparative data indicate that
      reviparin is at least as well tolerated as heparin and enoxaparin sodium.
      However, in a large (n = 1,279) trial there were significantly fewer major
      bleeding episodes in patients receiving reviparin than in patients given the oral
      anticoagulant acenocoumarol. The most commonly reported adverse events in
      therapeutic trials have been intraoperative blood loss and postoperative bleeding
      complications such as wound haematoma, bruising and injection site haemorrhage.
      Reviparin was also well tolerated in 2 studies in children aged < or = 16 years.
      CONCLUSION: Reviparin has shown efficacy in the treatment of established DVT and
      in the prevention of postoperative DVT after moderate and high risk surgery and
      was as effective as enoxaparin sodium or acenocoumarol in patients undergoing hip
      replacement surgery. As an effective and well tolerated antithrombotic agent,
      reviparin is likely to assume a significant role in the treatment and prevention
      of DVT, as it appears to have a preferable tolerability profile to subcutaneous
      heparin after moderate risk surgery and is at least as effective as intravenous
      heparin in the treatment of established DVT.

PMID- 11465878
TI  - Perindopril/indapamide 2/0.625 mg/day: a review of its place in the management of
      hypertension.
AB  - The fixed low-dose combination of the ACE inhibitor perindopril and the non
      thiazide diuretic indapamide has been evaluated in the management of patients
      with mild to moderate hypertension. Combination therapy aims to improve overall
      therapeutic efficacy while minimising adverse effects. In well-designed
      multicentre clinical trials, perindopril/indapamide at doses ranging from 2/0.625
      to 8/2.5 mg/day was significantly more effective than placebo in achieving
      adequate blood pressure (BP) control. A similar reduction in supine BP was
      observed when combined perindopril/indapamide 2/0.625 mg/day was compared with
      losartan 50 mg/day or atenolol 50 mg/day. Similar reductions in 24-hour
      ambulatory BP were also seen with perindopril/indapamide 2/0.625 mg/day and
      irbesartan 150 mg/day. However, response and normalisation rates were
      significantly higher with combination therapy than with losartan or irbesartan
      monotherapy. Combined perindopril/indapamide 2/0.625 mg/day therapy effectively
      reduced BP in elderly patients aged 65 to 85 years to a significantly greater
      extent than either atenolol 50 mg/day or placebo. Supine BP was also normalised
      in approximately two-thirds of patients in a small noncomparative trial in
      patients with hypertension and renal impairment. Low-dose perindopril/indapamide
      2/0.625 mg/day was well tolerated in clinical trials; the most common adverse
      events were headache and cough. Hypokalaemia, associated with the use of
      diuretics, occurred with a higher incidence with combined perindopril/indapamide
      2/0.625 mg/day therapy than with either atenolol 50 mg/day or placebo.
      Perindopril/indapamide 2/0.625 mg/day has shown efficacy in well designed
      comparative trials with atenolol, losartan and irbesartan including elderly
      patients and patients with renal impairment. Studies comparing this dosage of
      perindopril/ indapamide with other combination therapies would be beneficial in
      allowing the place of perindopril/indapamide to be more accurately determined.
      The fixed-low dose combination of perindopril/indapamide provides a promising and
      well tolerated treatment option in the management of patients with mild to
      moderate hypertension.

PMID- 11465879
TI  - A method for assessing the regional vibratory pattern of vocal folds by analysing
      the video recording of stroboscopy.
AB  - Stroboscopy and kymography have been used to examine the motional abnormality of
      vocal folds and to visualise their regional vibratory pattern. In a previous
      study (Laryngoscope, 1999), we introduced the conceptual idea of
      videostrobokymography, in which we applied the concept of kymography on the pre
      recorded video images using stroboscopy, and showed its possible clinical
      application to various disorders in vocal folds. However, a more detailed
      description about the software and the mathematical formulation used in this
      system is needed for the reproduction of similar systems. The composition of
      hardwares, user-interface and detail procedures including mathematical equations
      in videostrobokymography software is presented in this study. As an initial
      clinical trial, videostrobokymography was applied to the preoperative and
      postoperative videostroboscopic images of 15 patients with Reinke's edema. On
      preoperative examination, videostrobokymograms showed irregular pattern of
      mucosal wave and, in some patients, a relatively constant glottic gap during
      phonation. After the operation, the voice quality of all patients was improved in
      acoustic and aerodynamic assessments, and videostrobokymography showed clearly
      improved mucosal waves (change in open quotient: mean +/- SD= 0.11 +/- 0.05).

PMID- 11465880
TI  - Cephalometric image analysis and measurement for orthognathic surgery.
AB  - Automatic identification of landmarks in cephalometry is very important and
      useful for orthognathic surgery. A computerised automatic cephalometric analysis
      system (CACAS), based on image processing, is presented. For an original X-ray
      image, median filtering and histogram equalisation are used to improve image
      quality. The edge of an X-ray image is detected by a wavelet transform and Canny
      filter. Seventeen landmarks in cephalometry are successfully identified by
      knowledge-based edge tracing and changeable templates. Seventy-three measurements
      based on distances, angles and ratios between landmarks are computed
      automatically. The reliability of the landmarks and the validity of the
      measurements are compared for automatic and manual operation. The values of
      measurements obtained by CACAS are more precise and reliable: the mean error for
      linear measurements is less than 0.9mm; the mean error for angular measurements
      is less than 1.2 degrees. The rate of validity is over 80%, even if the image
      quality is poor. For an image with a high signal-to-noise ratio, the rate of
      validity of landmarking and measurements using the CACAS system is over 90%.

PMID- 11465881
TI  - Image processing used to harness blinking as a channel of communication and
      control for physically disabled people.
AB  - Sophisticated mathematical algorithms (such as differencing, thresholding,
      aggregation and statistical analysis of skin colours) are used to compare
      successive frames of computer-captured images of the face. From these, changes in
      state of the eyes are determined and are used to detect blinks. A recognition
      performance of 83.74 +/- 0.03% is achieved over five subjects with a low rate of
      false positives 2.71 +/- 0.01%. A logical decision rule identifies purposeful
      blinks and applies them to control either a custom-designed communication package
      or an external device.

PMID- 11465882
TI  - Diabetic feet at risk: a new method of analysis of walking foot pressure images
      at different levels of neuropathy for early detection of plantar ulcers.
AB  - Studies were performed on a large number of diabetic patients with three levels
      of plantar sensation loss by analysing walking foot pressure images in the
      frequency domain. The feet of diabetic subjects were scanned over ten specified
      areas using Semmes-Weinstein's nylon monofilaments to determine quantitatively
      the three levels of neuropathy. A new parameter, the power ratio (PR, ratio of
      high frequency power to the total power in an image) was used to distinguish
      discretely between normal and diabetic feet in three levels of sensation loss.
      Analysis of results showed that the differences in PR values for diabetic feet
      (in all three levels of sensation loss) compared to normal feet were found to be
      highly significant (p<0.0005) in the areas of the foot where there was a high
      incidence of plantar ulcer formation, even at the early stage of neuropathy
      characterised by a sensation level of 45mN. This result could help in the early
      detection of plantar ulcer formation in the initial stage of sensation loss and
      may be utilised by orthopaedic surgeons to consider early corrective methods to
      protect these feet from further damage due to neuropathic ulcer formation.

PMID- 11465883
TI  - Detecting absolute human knee angle and angular velocity using accelerometers and
      rate gyroscopes.
AB  - Knee joint angle and angular velocity were calculated in real time during
      standing up and sitting down. Two small modules comprising rate gyroscopes and
      accelerometers were attached to the thigh and shank of two able-bodied volunteers
      and one T5 ASIA(A) paraplegic assisted by functional electrical stimulation
      (FES). The offset and drift of the rate gyroscopes was compensated for by auto
      resetting and auto-nulling algorithms. The tilt of the limb segments was
      calculated by combining the signals of the accelerometer and the rate gyroscope.
      The joint angle was calculated as the difference in tilt of the segments. The
      modules were also tested on a two-dimensional model. The mean differences between
      the rate gyroscope-accelerometer system and the reference goniometer for the
      model, able-bodied and paraplegic standing trials were 2.1 degrees, 2.4 degrees
      and 2.3 degrees respectively for knee angle and 2.3 degrees s(-1), 5.0 degrees s(
      1) and 11.8 degrees s(-1) respectively for knee velocity. The rate gyroscope
      accelerometer system was more accurate than using the accelerometer as a tilt
      meter, possibly due to the greater bandwidth of the rate gyroscope-accelerometer
      system.

PMID- 11465884
TI  - Digital densitometric determination of relative coronary flow distributions.
AB  - In clinical cardiology, stenosis in a coronary artery is measured on the basis of
      visual assessment. The reading of coronary arteriograms leads, however, to large
      inter- and intra-observer variability. Image analysis and computer assistance
      result in a more consistent assessment, but this approach is mainly based upon
      static geometric parameters, such as diameter reduction of a segment of the
      stenosed artery. A more functional, physiological measurement is thus desirable.
      This can be realised by measuring the difference between the normal coronary
      blood flow and the increased flow under hyperaemic conditions, yielding the so
      called coronary flow reserve (CFR). In clinical practice, however, this method is
      difficult and time-consuming. A less demanding approach is reported, in which
      relative flow distributions are determined densitometrically from digital
      angiograms acquired under basal and hyperaemic conditions. The proposition is
      that, if the relative flow distribution in hyperaemic state differs from that
      during rest, the functional severity of a stenosis downstream from the
      bifurcation can be indicated. The new approach is validated by comparing the
      results of a theoretical model for steady flow with a flow phantom experiment for
      steady and pulsatile flow. The obtained flow ratios correlate very well, both in
      steady and pulsatile flow, with correlation coefficients exceeding 0.95.

PMID- 11465885
TI  - Error analysis of a natural breathing calibration method for respiratory
      inductive plethysmography.
AB  - Respiratory volumes are measured non-invasively by recording rib cage and
      abdominal motions using respiratory inductive plethysmography (RIP). Qualitative
      diagnostic calibration (QDC) of RIP is based on the natural variability in the
      relative rib-cage-to-abdomen contribution during tidal breathing. ODC does not
      require subject cooperation but it has previously been shown that accuracy may
      deteriorate when breathing pattern changes. The aim of this study was to
      investigate the causes and situations where QDC accuracy deteriorates. The QDC
      method was compared to PRA (calibration during voluntarily preferential rib cage
      or abdomen breathing) in ten adults. A reference RIP calibration was obtained
      from all validation data (REF). The PRA method had better accuracy than the ODC
      method (p<0.01). The volumetric error ranged between 10% and 136% with QDC and
      between 5% and 33% with PRA. The PRA calibration factors were within 6% of those
      from REF, while the QDC rib-cage factor was underestimated by 15% and the
      abdominal factor was overestimated by 38%. Small natural variability in the
      relative rib-cage-to-abdomen contribution was related to poor accuracy. Each
      compartment's variability depended on its magnitude, which is a violation of the
      QDC assumptions.

PMID- 11465886
TI  - Time-frequency microstructure of event-related electro-encephalogram
      desynchronisation and synchronisation.
AB  - A new method is presented for the analysis of event-related EEG phenomena, in
      particular event related desynchronisation (ERD) and event related
      synchronisation (ERS) related to a voluntary movement; the method offers: high
      time-frequency resolution and, hence, increased ERD/ERS sensitivity (especially
      in the gamma band, where improvement can exceed an order of magnitude); the
      ability to analyse the whole picture of energy changes at once, without setting a
      priori the analysed frequency bands; and a parametric description of the signal's
      structures. The main idea is based upon averaging energy distributions of single
      EEG trials in the time-frequency plane. As the estimator for the signal's energy
      density, matching pursuit is chosen, with stochastic Gabor dictionaries. Other
      possible estimates are presented on a simulated signal and discussed briefly. The
      consistency of the results with previous findings is evaluated on the data from a
      classical voluntary finger movement experiment.

PMID- 11465887
TI  - Dynamics of the level of deterministic chaos associated with gastric electrical
      uncoupling in dogs.
AB  - This study investigated the impact of gastric electrical uncoupling on the
      dynamics of the level of deterministic chaos in cutaneous gastric electrical
      signals. Eight-channel electrogastrograms (EGG) were recorded from 16 unconscious
      dogs. Controlled gastric electrical uncoupling was introduced by
      circumferentially cutting the whole gastric muscle at two different locations.
      Three separate 30-min EGG recordings were obtained from each dog in the three
      different states (basal, after the first cut, and after the second cut). The
      Lyapunov exponents were calculated from sixteen 6.31-min intervals with 75%
      overlap obtained from each channel in each state. Inadequate EGG signals from
      which the Lyapunov exponent could not be reliably calculated were quantitatively
      discarded. The variance and the standard deviation of the three Lyapunov exponent
      distributions obtained from each channel were studied, and the mean values were
      subjected to a Student t-test. In 65.6% of all studied channels, the level of
      chaos was significantly different (p< 0.01) after the first cut compared to the
      basal state, but no predominant direction of variation was observed (47. 7%
      increment vs. 52.5% decrement). After the second cut, 63.6% of the channels
      studied showed significantly greater Lyapunov exponent compared to the basal
      state, and 63.1% exhibited significantly greater (p< 0.01) level of chaos
      compared to the intercut state. The dynamics of the level of deterministic chaos
      in canine electrogastrograms is highly sensitive to severe gastric electrical
      uncoupling. Moreover, some channel configurations seem to be more sensitive than
      others in detecting uncoupling.

PMID- 11465888
TI  - Detection of abnormality in the electrocardiogram without prior knowledge by
      using the quantisation error of a self-organising map, tested on the European
      ischaemia database.
AB  - Most systems for the automatic detection of abnormalities in the ECG require
      prior knowledge of normal and abnormal ECG morphology from pre-existing
      databases. An automated system for abnormality detection has been developed based
      on learning normal ECG morphology directly from the patient. The quantisation
      error from a self-organising map 'learns' the form of the patient's ECG and
      detects any change in its morphology. The system does not require prior knowledge
      of normal and abnormal morphologies. It was tested on 76 records from the
      European Society of Cardiology database and detected 90.5% of those first
      abnormalities declared by the database to be ischaemic. The system also responded
      to abnormalities arising from ECG axis changes and slow baseline drifts and
      revealed that ischaemic episodes are often followed by long-term changes in ECG
      morphology.

PMID- 11465889
TI  - Reliability of transfer function estimates in cardiovascular variability
      analysis.
AB  - Transfer function (TF) analysis is a widely diffused technique in the assessment
      of the relationship between short-term cardiovascular variability signals,
      particularly blood pressure, heart rate and respiration. To guarantee the
      reliability of the estimates, a conventional threshold of 0.5 on the magnitude
      squared coherence (MSC) is commonly used, although (i) other analysis parameters
      play a role and (ii) lower values of MSC are frequently unavoidable in
      physiological systems. In this study, computer simulations are performed to
      assess the dependency of the bias and standard deviation (SD) of TF estimates on
      record length (RL), spectral window bandwidth (Bw) and MSC; to evaluate the
      accuracy of theoretical expressions for the computation of the confidence
      interval (CI) of the estimates; and to assess, in some representative situations,
      how faithfully observed TF shapes reproduce the underlying true functions in
      conditions of very low MSC. The accuracy of TF estimates increases non-linearly
      with increasing RL, and the benefit over 7 min is small. Using this RL, the
      relative bias for the TF modulus is < 10% for MSC > 0.2. Estimates of TF phase
      are unbiased. The SD of both the modulus and phase increases linearly as the MSC
      decrease to 0.4 and then, for lower MSC, increases markedly with nonlinear
      behaviour. Bw= 0.03Hz appears to be most suitable to reduce the error, preserving
      spectral resolution. CIs for the TF phase are highly reliable, whereas those for
      the modulus tend to be slightly narrower than the nominal value at high coherence
      values. Major features of the TF shape appear to be preserved in simulations with
      very low MSC. The major problem in TF estimation is the sharp increase in the
      variability of the measurements as the coherence decreases towards the lowest
      values. The combination of RL > or = 420s and Bw= 0.03Hz should be suggested in
      short-term cardiovascular variability studies. Although basic features of the
      true TF can be recovered even when the MSC is < 0.5, much greater values can be
      necessary when accurate point estimates are needed. Theoretical expressions for
      the computation of confidence intervals of the TF are adequate for practical
      purposes.

PMID- 11465890
TI  - Spectral analysis of heart rate variability using the integral pulse frequency
      modulation model.
AB  - Spectral analysis of heart rate variability (HRV) is a widely accepted approach
      for assessment of cardiac autonomic function and its relationship to numerous
      disorders and diseases. As a rule, the non-parametric methods for HRV spectral
      analysis are tested using the integral pulse frequency modulation (IPFM) model.
      However, published results with simulated HRV signals show differences requiring
      further development of the existing methods. With the aim of improving estimation
      accuracy, an entirely IPFM-based method for HRV analysis is investigated.
      According to this method, the spectra are computed by finding the least squares
      solution of two matrix equations that are derived using the IPFM model and
      involve irregular samples of a signal representing the HRV. The method is
      validated with various synthesised signals (in all tests, the relative errors of
      the power estimates at the modulating frequencies are within 3%, and the relative
      power of the spurious terms is less than 0.8% only) and is furthermore applied to
      the spectral analysis of R-R interval series obtained from diabetic children. The
      results, with simulated and real HRV signals, show that the developed method
      yields very accurate estimations of the spectral region below half the mean heart
      rate. Moreover, it allows the detection and assessment of certain genuine
      modulating components beyond the traditional frequency limit of the HRV spectra.

PMID- 11465891
TI  - Design of a wavelet interpolation filter for enhancement of the ST-segment.
AB  - A wavelet interpolation filter (WIF) is designed for the removal of motion
      artifacts in the ST-segment of stress ECGs. The WIF consists of two parts. One
      part is a wavelet transform that decomposes the stress ECG signal into several
      frequency bands using a Haar wavelet. The other part is an interpolation method,
      such as the spline technique, that is used to enhance the reconstruction
      performance of the signal decomposed by the wavelet transform. To evaluate the
      performance of the WIF, three indices are used: signal-to-noise ratio (SNR),
      reconstruction square error (RSE) and standard deviation (SD). The MIT/BIH
      arrhythmia database, the European ST-T database and the triangular wave are used
      for evaluation. A noisy ECG signal, corrupted by motion artifacts, is simulated
      by the addition of two types of random noise to the original ECG signal. For
      comparison, three indices for the other methods are also computed: mean, median
      and hard thresholding. The performance of the WIF shows that RSE, SNR and SD are
      392.7, 18.3dB and 2.6, respectively, in the case of a noisy signal with an SNR of
      7.1 dB. This result is much better than those for the other methods.

PMID- 11465892
TI  - Radial basis function neural network approach for the diagnosis of coronary
      artery disease based on the standard electrocardiogram exercise test.
AB  - The purpose of the paper is the evaluation of a radial basis function neural
      network as a tool for computer aided coronary artery disease diagnosis based on
      the results of the traditional ECG exercise test. The research was performed
      using 776 data records from an exercise test (297 records from healthy patients
      and 479 from ill patients) confirmed by coronary arteriography results. Each
      record described the state of the patient, provided input data for the neural
      network, included the level and slope of an ST segment of a 12-lead ECG signal
      made at rest and after effort, heart rate, blood pressure, load during the test,
      and occurrence of coronary pain, coronary arteriography, correct output pattern
      for the neural network, and verified the existence (or not) of more than 50%
      stenosis of the particular coronary vessels. Radial basis function neural
      networks for coronary artery disease diagnosis were optimised by choosing the
      type of radial function, the method of training (setting the number of centres
      and their dimensions), and regularisation. The best network correctly recognised
      over 97% of cases from a 400-element test set, diagnosing not only the patients'
      condition (simple 'healthy/unhealthy' diagnosis), but also pointing out
      individual unhealthy/stenosed vessels.

PMID- 11465893
TI  - Front-end architecture for a multi-frequency electrical impedance tomography
      system.
AB  - This paper provides a critical review of a number of the primary aspects of EIT
      system hardware presented in the literature. A thorough analysis of injection and
      measurement errors is presented to provide clarifying extensions to that provided
      by previous authors. From this basis, it proposes a novel design for a
      distributed parallel multi-frequency EIT system. The system described is modular,
      employs active electrodes to maximise CMRR (common mode rejection ratio) and was
      designed to employ digitally generated current injection and digital demodulation
      of the acquired signals.

PMID- 11465894
TI  - Comparison of time-frequency distribution techniques for analysis of spinal
      somatosensory evoked potential.
AB  - Spinal somatosensory evoked potential (SSEP) has been employed to monitor the
      integrity of the spinal cord during surgery. To detect both temporal and spectral
      changes in SSEP waveforms, an investigation of the application of time-frequency
      analysis (TFA) techniques was conducted. SSEP signals from 30 scoliosis patients
      were analysed using different techniques; short time Fourier transform (STFT),
      Wigner-Ville distribution (WVD), Choi-Williams distribution (CWD), cone-shaped
      distribution (CSD) and adaptive spectrogram (ADS). The time-frequency
      distributions (TFD) computed using these methods were assessed and compared with
      each other. WVD, ADS, CSD and CWD showed better resolution than STFT. Comparing
      normalised peak widths, CSD showed the sharpest peak width (0.13+/-0.1) in the
      frequency dimension, and a mean peak width of 0.70+/-0.12 in the time dimension.
      Both WVD and CWD produced cross-term interference, distorting the TFA
      distribution, but this was not seen with CSD and ADS. CSD appeared to give a
      lower mean peak power bias (10.3%+/-6.2%) than ADS (41.8%+/-19.6%). Application
      of the CSD algorithm showed both good resolution and accurate spectrograms, and
      is therefore recommended as the most appropriate TFA technique for the analysis
      of SSEP signals.

PMID- 11465895
TI  - Identification of physiological systems: estimation of linear time-varying
      dynamics with non-white inputs and noisy outputs.
AB  - A new technique to identify linear time-varying systems from ensembles of input
      output realisations is presented. First, a correlation-based least-squares method
      is derived. This method consists of solving, for each sampling time, a matrix
      equation involving estimates of the input autocorrelation and input-output cross
      correlation functions computed from data across the ensemble. Then, the matrix
      inverse needed to solve this matrix equation is replaced with a pseudo-inverse.
      The model is thus constrained to describe only those components of the dynamics
      that can be reliably identified. Ignoring 'unidentifiable' components has
      virtually no adverse effect on the predicted outputs. Simulation results
      demonstrate that the pseudoinverse technique yields more reliable estimates of
      the dynamics than a previously proposed least-squares technique when the inputs
      are coloured and the output signal-to-noise ratio (SNR) is low. With the input
      spectrum flat up to approximately 10% of the sampling rate and an output SNR of
      5dB, the mean variance accounted for (VAF) between the true instantaneous impulse
      response functions (IRFs) and the instantaneous IRFs estimated with the least
      squares technique was 0.2%. In contrast, the mean VAF between the true
      instantaneous IRFs and the instantaneous IRFs estimated with the pseudoinverse
      technique was 89.0%.

PMID- 11465896
TI  - Automatic identification of metaphase spreads and nuclei using neural networks.
AB  - The mitotic index (MI) is an important measure in cell proliferation studies.
      Determination of the MI is usually made by light-microscope analysis of slide
      preparations. The analyst identifies and counts thousands of cells and reports
      the percentage of mitotic shapes found among the interphase nuclei. Full
      automation of this process is an ambitious task, because there can exist very few
      mitotic shapes among hundreds of nuclei and thousands of artifacts, resulting in
      a high probability of false positives, i.e. objects erroneously identified as
      mitosis or nuclei. A semi-automated approach for MI calculation is reported,
      based on the development of a neural network (NN) for automatic identification of
      metaphase spreads and stimulated nuclei in digital images of microscope
      preparations at 10X magnification. After segmentation of the objects on each
      image, ten different morphometrical, photometrical and textural features are
      measured on each segmented object. An NN is used to classify the feature vectors
      into three classes: metaphases, nuclei and artifacts. The system has been able to
      classify correctly approximately 91% of the objects in each class, in a test set
      of 191 mitosis, 331 nuclei and 387 artifacts, obtained from 30 different
      microscope slides. Manual editing of false positives from the metaphase
      classification results allows the calculation of the MI with an error of 6.5%.

PMID- 11465897
TI  - Temporal changes in cytoskeletal organisation within isolated chondrocytes
      quantified using a novel image analysis technique.
AB  - This paper examines temporal changes in the organisation of the cytoskeleton
      within isolated articular chondrocytes cultured for up to 7 days in agarose
      constructs. Fluorescent labelling and confocal microscopy were employed to
      visualise microtubules (MT), vimentin intermediate filaments (VIF) and actin
      microfilaments (AMF). To quantify the degree of cytoskeletal organisation within
      populations of cells, a novel image analysis technique has been developed and
      fully characterised. Organisation was quantified in terms of an Edge Index, which
      reflects the density of 'edges' present within the confocal images as defined by
      a Sobel digital filter. This parameter was shown to be independent of image
      intensity and, for all three cytoskeletal components, was validated statistically
      against a visual assessment of organisation. Both MT and VIF exhibited fibrous
      networks extending throughout the cytoplasm, while AMF appeared as punctate units
      associated with the cell membrane. The use of the Edge Index parameter revealed
      statistical significant temporal variation, in particular associated with VIF and
      AMF. These findings indicate the possibility of cytoskeletal mediated temporal
      variation in many aspects of cell behaviour following isolation from the intact
      tissue. Furthermore, the image analysis techniques are likely to be useful for
      future studies aiming to quantify changes in cytoskeletal organisation.

PMID- 11465898
TI  - Baler and compactor-related deaths in the workplace--United States, 1992-2000.
AB  - Equipment that compacts and bales loose solid waste materials into denser, more
      easilytransported units is common in refuse disposal and recycling and is used
      routinely at recycling centers, manufacturing facilities, and retail and
      wholesale stores to compress paper, textiles, metals, plastic, and other
      material. Persons operating balers and compactors can become caught by the
      powered rams of the compression chambers while using these machines. Risk factors
      resulting from these incidents have been identified through surveillance findings
      and results of investigations conducted by CDC's National Institute for
      Occupational Safety and Health (NIOSH) Fatality Assessment and Control Evaluation
      (FACE) program and the Bureau of Labor Statistics Census of Fatal Occupational
      Injuries (CFOI), a nationwide multisource reporting system for occupational
      deaths. This report describes the results of two baler and compactor-related
      investigations conducted during 1992-2000, summarizes surveillance data from 1992
      through 1998, which indicated that some employers and workers may have been
      unaware of the hazards of operating or working near compacting and baling
      equipment, and suggests safety recommendations for preventing future incidents.

PMID- 11465899
TI  - Nonfatal occupational injuries and illnesses treated in hospital emergency
      departments--United States, 1998.
AB  - The National Electronic Injury Surveillance System (NEISS) includes data about
      nonfatal occupational injuries and illnesses treated in U.S. hospital emergency
      departments (EDs). This report summarizes 1998 injury and illness estimates based
      on NEISS, which indicate that the magnitude and patterns of nonfatal occupational
      injuries and illnesses were comparable to estimates reported for 1996 (1).
      Younger workers continue to have the highest rates of work-related injuries and
      illnesses; therefore, interventions should address the health and safety needs of
      young workers, most of whom lack substantial experience in the work place.

PMID- 11465900
TI  - Fatal occupational injuries--United States, 1980-1997.
AB  - CDC monitors deaths from occupational injuries through the National Traumatic
      Occupational Fatalities (NTOF) surveillance system (1,2). This report provides an
      overview of traumatic occupational deaths among civilian workers from NTOF from
      1980 through 1997, the most recent year for which data are available. The data
      presented in this report indicate a decrease in occupational deaths overthis
      period with mining, agriculture/forestry/fishing, and construction having the
      highest death rates; motor-vehicle crashes were the leading cause of injury
      related deaths for U.S. workers. State health departments and others involved in
      prevention of occupational injuries can use the data to prioritize intervention
      programs.

PMID- 11465901
TI  - Progress toward global poliomyelitis eradication, 2000.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally
      by 2000 (1). Substantial progress toward this goal has been reported from all six
      World Health Organization (WHO) regions; 20 countries reported poliovirus
      transmission in December 2000 compared with 30 in 1999. WHO has prepared a global
      action plan that anticipates certification of polio eradication in 2005 (2). This
      report summarizes the status of the eradication effort and describes the
      remaining tasks to be completed to reach global polio eradication

PMID- 11465902
TI  - Prevalence of arthritis--United States, 1997.
AB  - Arthritis and other rheumatic conditions (i.e., arthritis) are among the most
      prevalent diseases in the United States (1) and the most frequent cause of
      disability (2). In 1985, an estimated 35 million persons were affected by
      arthritis (3); in 1990 (1), a study using a broader arthritis definition
      estimated that 38 million were affected. To better characterize these conditions,
      CDC analyzed a variety of data for 1997 using common definitions from the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM). The findings of one such analysis in the National Health Interview
      Survey (NHIS) indicated that, in 1997, the prevalence of persons with arthritis
      had increased by approximately 750,000 per year since 1990. Findings also support
      earlier projections that by 2020, 60 million persons may be affected by arthritis
      and that the activities of 11.6 million persons may be limited by arthritis (1).
      More widespread implementation of existing interventions may reduce the
      occurrence and progression of arthritis.

PMID- 11465903
TI  - Trends in blood lead levels among children--Boston, Massachusetts, 1994-1999.
AB  - Data from the National Health and Nutrition Examination Survey and national
      childhood blood lead surveillance data from 19 states indicated that average
      blood lead levels (BLLs) in young children decreased during the late 1990s (1-3).
      The proportion of children tested who had BLLs >10 microg/dL declined from 10.5%
      in 1996 to 7.6% in 1998, although the proportion was higher in certain counties
      (3). To determine whether a similar decline had occurred in Boston,
      Massachusetts, where a high proportion of children are tested each year, and
      whether any changes were similar in high- and low-risk neighborhoods, CDC, in
      collaboration with the Boston Childhood Lead Poisoning Prevention Program
      (BCLPPP) performed an analysis of BLLs among children aged 6-72 months in Boston
      during 1994-1999. The results indicate that BLLs in Boston declined during this
      period, but because of the geographic variation in lead exposure, continued
      surveillance will be necessary to eliminate childhood lead poisonings.

PMID- 11465904
TI  - National estimates of nonfatal injuries treated in hospital emergency departments
      -United States, 2000.
AB  - On July 1, 2000, the Consumer Product Safety Commission's (CPSC) National
      Electronic Injury Surveillance System (NEISS) was expanded to collect data on all
      types and external causes of nonfatal injuries and poisonings treated in U.S.
      hospital emergency departments (EDs). This augmented system, called NEISS All
      Injury Program (NEISS-AIP), is a collaborative effort between CDC's National
      Center for Injury Prevention and Control and CPSC. This report presents
      annualized national estimates using NEISS-AIP data obtained during July 1
      September 30, 2000, which indicate that approximately 31,000,000 persons were
      treated for nonfatal injuries in EDs in 2000. Although most of the injuries were
      unintentional, an estimated 1,973,000 were violence-related. Data from NEISS-AIP
      can be used for monitoring temporal trends in nonfatal injuries by mechanism and
      intent of injury.

PMID- 11465905
TI  - Trends in injection drug use among persons entering addiction treatment--New
      Jersey, 1992-1999.
AB  - Injection drug use is associated with high risk for transmission of bloodborne
      infections, including human immunodeficiency virus (HIV) and hepatitis B and C.
      Since 1993, the proportion of persons admitted to New Jersey addiction treatment
      centers for illicit drug use who reported injecting drugs has increased,
      reversing a decline that began in approximately 1980 (1; Community
      EpidemiologyWork Group, unpublished data, 2000). This report summarizes an
      analysis of trends in injection drug use among persons admitted to New Jersey
      addiction treatment programs during 1992-1999; the findings suggest substantial
      increases in injection use among young adult heroin users throughout the state
      and an increase in heroin use among young adults who reside in suburban and rural
      New Jersey.

PMID- 11465906
TI  - Soft tissue infections among injection drug users--San Francisco, California,
      1996-2000.
AB  - Soft tissue infections (STIs), including abscesses and cellulitis, are a common
      complication of injection drug use. In 1997, 54 (32%) of 169 injection drug users
      (IDUs) in one San Francisco neighborhood had a drug-injection-related abscess or
      cellulitis (1). To characterize STIs among IDUs, data from San Francisco General
      Hospital (SFGH) discharge and billing records were analyzed. This report
      summarizes the results of that analysis and presents the case report of one IDU
      with an STI. The findings indicate that STIs are among the most common diagnoses
      among patients admitted to SFGH. Preventing STIs among IDUs in San Francisco will
      require coordinated action involving health-care providers, public health
      agencies, substance abuse treatment, community outreach, syringe exchange
      programs, IDUs, and community-based organizations.

PMID- 11465907
TI  - Update: syringe exchange programs--United States, 1998.
AB  - Syringe exchange programs (SEPs) provide sterile syringes in exchange for used
      syringes to reduce the transmission of human immunodeficiency virus (HIV) and
      other bloodborne infections associated with the reuse of potentially blood
      contaminatedsyringes among injection drug users (IDUs) (1). This report
      summarizes a survey of 1998 SEP activities in the United States and compares them
      with 1994-1997 SEP activity surveys (1-3). SEPs are an increasingly common HIV
      prevention approach that offer a range of public health services in addition to
      syringe exchange.

PMID- 11465908
TI  - Hepatitis B vaccination for injection drug users--Pierce County, Washington,
      2000.
AB  - Hepatitis B vaccination has been recommended for injection drug users (IDUs)
      since 1982, but vaccination coverage of IDUs remains low (1), and outbreaks of
      hepatitis B among IDUs continue to occur. An outbreak of hepatitis B primarily
      among IDUs in Pierce County, Washington, detected in April 2000, included 60
      cases and resulted in three deaths among IDUs co-infected with hepatitis delta
      virus. A program to administer hepatitis B vaccine to IDUs was implemented to
      control the outbreak, and the number of cases identified decreased from 13 per
      month in May to two cases since November. This report describes a vaccination
      program during which IDUs accepted hepatitis B vaccination provided free of
      charge in community-based settings and illustrates how effective hepatitis B
      vaccination programs targeted at IDUs can be implemented through collaborations
      between departments of health and corrections and community organizations.

PMID- 11465909
TI  - Outbreak of Legionnaires' disease among automotive plant workers--Ohio, 2001.
AB  - During March 12-15, 2001, four cases of Legionnaires' disease (LD) among workers
      at an automotive engine manufacturing plant (plant X) were reported to the
      Cuyahoga County Board of Health, Cleveland, Ohio; all four diagnoses were
      confirmed by Legionella urine antigen. Illness onset among the four workers
      occurred during March 2-4; two workers died. Beginning March 14, CDC assisted
      state and local health departments with an investigation to identify new cases
      and potential sources of Legionella transmission in the plant. This report
      summarizes the investigation; findings indicate an epidemiologic association with
      exposure to one of the plant finishing lines but did not identify a specific
      source.

PMID- 11465910
TI  - Update: outbreak of acute febrile respiratory illness among college students-
      Acapulco, Mexico, March 2001.
AB  - On March 30, CDC was notified by the Pennsylvania Department of Health of an
      acute febrile respiratory illness characterized by fever, chills, dry cough,
      chest pain, and headache among college students who traveled to Acapulco during
      March 2001. Initial laboratory testing indicated that most students had
      histoplasmosis, an infection caused by the soil-inhabiting fungus, Histoplasma
      capsulatum. While in Acapulco, most ill students had stayed at the Calinda Beach
      Hotel. This report updates the investigation of the outbreak and presents
      possible evidence of ongoing transmissions.

PMID- 11465911
TI  - Pregnancy-related deaths among Hispanic, Asian/Pacific Islander, and American
      Indian/Alaska Native women--United States, 1991-1997.
AB  - In the United States in 1997, the Hispanic, Asian/Pacific Islander, and American
      Indian/ Alaska Native population represented 16% of all reproductive-age women
      (aged 15-49 years) but accounted for 23.5% of all live births (1,2). Although
      statistics by race/ethnicity are available for maternal deaths (3), pregnancy
      related mortality ratios (PRMRs) have been reported regularly only for black and
      white women. Pregnancy-related deaths in Hispanic women have been studied (4);
      however, combining pregnancy-related mortality risk among Asians/Pacific
      Islanders and American Indians/Alaska Natives into an "other" category masks
      differences in their health status. This report presents PRMRs among Hispanic,
      Asian/Pacific Islander, and American Indian/Alaska Native women in the United
      States during 1991-1997. The findings indicate that these groups have higher
      PRMRs than non-Hispanic white (white) women and lower ratios than non-Hispanic
      black (black) women and underscore the need for targeted interventions that
      address the maternal health needs of racial/ethnic minority women.

PMID- 11465912
TI  - Pharmacological differences among angiotensin II receptor antagonists.
AB  - Angiotensin II AT1 receptor antagonists (AIIRAs) have demonstrated efficacy
      similar to other classes of antihypertensive agents as well as "placebo-level"
      tolerability at all doses. Pharmacokinetic and pharmacodynamic studies provide a
      framework for understanding important intra-class dissimilarities. Disparity in
      antagonistic effects may be determined by in vivo responses to challenges of
      exogenous angiotensin II (Ang II) and by ex vivo/in vitro responses to a drug's
      biological activity by radioligand receptor assay (RRA). Two independent studies
      have been conducted in which irbesartan exhibited a more pronounced and longer
      lasting antagonism to the effects of exogenous Ang II than losartan and
      valsartan. Comparative trials have indicated that both irbesartan and candesartan
      show greater clinical efficacy in lowering blood pressure than losartan.
      Recently, we have compared the Ang II antagonistic properties of irbesartan 150
      mg/day and candesartan 8 mg/day. Both drugs block AT1 receptors with
      "insurmountable" antagonism and demonstrate a long duration of action. While both
      irbesartan and candesartan showed a similar degree of antagonistic activity in
      vivo, distinctly higher antagonistic activity in plasma was found for irbesartan
      by RRA at all time-points. Furthermore, plasma renin activity during periods with
      high antagonistic activity was significantly higher, and aldosterone levels
      following Ang II stimulation were blunted to a greater extent, following
      administration of irbesartan. In summary, in the doses tested, irbesartan
      exhibits the strongest antagonism when compared with losartan, valsartan and
      candesartan. This finding may have clinical implications.

PMID- 11465913
TI  - Clinical differences among angiotensin II receptor antagonists.
AB  - The six major classes of antihypertensive agents prescribed worldwide are similar
      in efficacy but dissimilar in tolerability. Recently, the World Health
      Organization-International Society of Hypertension (WHO-ISH) concluded that
      agents from all six classes are suitable for the initiation and maintenance of
      antihypertensive therapy, including the newest class of agents, the angiotensin
      II receptor antagonists (AIIRAs). The ideal antihypertensive agent should be
      effective and well tolerated, as well as synergistic in blood pressure-lowering
      effects when combined with other agents. As monotherapy, AIIRAs have demonstrated
      efficacy similar to other classes of antihypertensive agents in numerous clinical
      trials. Several AIIRAs have also demonstrated enhanced efficacy when combined
      with a low dose of the diuretic hydrochlorothiazide (HCTZ). A well-known feature
      of this new class of agents is placebo-level tolerability; however, less is known
      about intra-class differences. Losartan, the first approved AIIRA, has become an
      important benchmark for within-class comparisons with respect to antihypertensive
      efficacy. Head-to-head comparisons between losartan and newer AIIRAs have been
      conducted; their cumulative results indicate that the antihypertensive effect and
      antagonistic activity of losartan may be the weakest among AIIRAs. In a recent
      clinical trial, we demonstrated that irbesartan produces statistically superior
      blood pressure reduction when compared to valsartan. This may have clinical
      implications for agent selection among the AIIRAs.

PMID- 11465914
TI  - Hypertension and diabetes: the scope of the problem.
AB  - Cardiovascular and renal diseases in diabetes stem from an accelerated form of
      atherosclerosis in both small and large blood vessels. Diabetic nephropathy is a
      clinical hallmark of microangiopathy and often leads to end-stage renal failure.
      Significantly, microalbuminuria is an independent predictor of cardiovascular
      morbidity and mortality in both the diabetic and non-diabetic population. In
      diabetic patients, it is also strongly associated with proliferative retinopathy,
      neuropathy and hypertension. Effective blood pressure reduction in patients with
      type 2 diabetes and diabetic nephropathy is known to reduce albuminuria, delay
      the progression of diabetic nephropathy, postpone renal failure and improve
      survival. These benefits have been demonstrated with a variety of blood pressure
      lowering agents, including beta-blockers, calcium channel blockers, diuretics and
      angiotensin-converting enzyme (ACE) inhibitors. Less is known about the renal
      effects of the newest class of antihypertensive agents, the angiotensin II
      receptor antagonists (AIIRAs). Irbesartan is an AIIRA that provides
      antihypertensive efficacy comparable to ACE inhibitors but with superior
      tolerability. The PRogram for Irbesartan Mortality and morbidity Evaluations
      (PRIME) is an important morbidity and mortality program encompassing the
      Irbesartan Diabetic Nephropathy Trial (IDNT) and the IRbesartan MicroAlbuminuria
      type 2 diabetes mellitus in hypertensive patients (IRMA II) study. PRIME is
      evaluating the effects of irbesartan in preventing diabetic nephropathy and end
      stage renal failure and in reducing cardiovascular events in high-risk
      hypertensive patients with type 2 diabetes. The trials were completed at the end
      of 2000.

PMID- 11465915
TI  - Hypertension control for a new era: emerging differences among AIIRAs.

PMID- 11465916
TI  - Achieving blood pressure targets in the management of hypertension.
AB  - The 1999 World Health Organization-International Society of Hypertension
      guidelines state that the goal of antihypertensive therapy should be to restore
      blood pressure to a level defined as normal (<130/85 mmHg). Yet, despite
      significant efforts in diagnosing and treating hypertension, blood pressure is
      normalized in less than one-third of hypertensive patients worldwide. Inadequate
      blood pressure control is most likely to occur when treatment is ineffective,
      intolerable or both. Hypertension is a heterogeneous disease involving several
      pressor systems. It is therefore not surprising that a single drug normalizes
      blood pressure in only a fraction of hypertensive patients. Co-administering two
      medications that lower blood pressure by different mechanisms generally increases
      antihypertensive efficacy. The angiotensin II receptor antagonist (AIIRA) class
      represents a new therapeutic option: a class of agents that provide blood
      pressure reduction similar to other classes of antihypertensives with the
      additional advantage of an excellent tolerability profile. The AIIRA irbesartan
      has demonstrated dose-related efficacy in reducing blood pressure as monotherapy
      and augmented efficacy in combination with low doses of the diuretic
      hydrochlorothiazide. Efforts should be directed to normalize blood pressure in
      every hypertensive patient by finding a drug regimen that is simultaneously
      effective and well tolerated.

PMID- 11465917
TI  - Clinical trials: present and future.
AB  - The past decade has seen a major expansion of clinical trials in amyotrophic
      lateral sclerosis (ALS). However, the perfectly-designed ALS trial remains
      elusive. Attempts to track the progression of the disease are affected by
      continual improvements in the care of patients. Comparing the effectiveness of
      different drugs is difficult because different primary endpoints are used in
      different studies. We also need to decide how much benefit we are aiming to
      achieve when studying a new treatment. The interpretation of animal models has
      also proved problematic, with results not being replicated in human studies.
      Moreover, promising phase I/II trial results have often not been confirmed by
      phase III studies. Our patients, meanwhile, are anxious to try any medication
      that may help. The ALS research community has learned a great deal from past
      trials and this will be greatly beneficial when evaluating the novel and
      combination therapies currently being developed. Effort must also be directed
      towards the search for objective markers for ALS.

PMID- 11465918
TI  - Clinical trials: the past, a lesson for the future.
AB  - Numerous drugs have been tested in amyotrophic lateral sclerosis with the
      expectation both that they will treat patients and improve our understanding of
      some of the basic mechanisms of the disease. Most of these trials were considered
      to be negative. Careful analysis of the trials does not allow us to clearly
      discard any of the tested drugs, or any of the suspected mechanisms. Expectations
      for the future are that: a) we need to be realistic about what to expect; b) we
      have to define clearly our end-points; c) we have to calculate the expected power
      before the trials, not after; and d) we have to improve our understanding of the
      pharmacology.

PMID- 11465919
TI  - Slowing down ALS--is this good or bad?
AB  - The availability of a drug that provides modest relief in ALS without altering
      its inevitable progression and end, has posed new ethical and economic problems
      for patients, caregivers and physicians. Early evidence suggests that riluzole
      does provide a short additional quality of life and economic benefit for patient
      and society. However, there is a clear need for additional therapies, even if the
      benefit is minor.

PMID- 11465920
TI  - Are there immunologically treatable motor neuron diseases?
AB  - Several studies have addressed the issue of a possible immunological involvement
      in the pathogenesis of amyotrophic lateral sclerosis (ALS) or motor neuron
      disease (MND), particularly when the disease was associated with cancer, lymphoma
      or other monoclonal gammopathies or with the presence of serum antibodies to
      neural antigens. The hypothesis of the existence of immunologically treatable MND
      was reinforced by the occasional report of MND patients responding to immune or
      cytostatic therapies and by the identification among those with a purely lower
      motor neuron syndrome (LMNS) of a motor neuropathy, presently known as multifocal
      motor neuropathy (MMN), which almost invariably responded to immune therapies.
      These observations have led to several attempts to treat patients with MND or
      LMNS, either idiopathic or associated with the above mentioned conditions, with a
      number of immune or cytostatic therapies. The aim of this review is to verify
      whether the available data provide enough evidence to support the concept of
      dysimmune MND and to justify the use in these patients of potentially harmful
      immune cytostatic therapies.

PMID- 11465921
TI  - ALS 2000: the past points to the future.
AB  - In this introductory review a number of issues concerning the direction of future
      research in ALS are addressed in relation to current understanding of this
      disorder and its treatment. The importance of understanding the pathways leading
      to motor neuron dysfunction and death is emphasized. Contemporary epidemiology,
      understandably focussed on genetic markers for familial ALS, needs to be widened
      to include as yet undocumented susceptibility-related genetic traits. Potential
      avenues for therapy are considered, and the fundamental contemporary issue of
      clinical measurement is discussed. Neglected aspects of contemporary research,
      including disturbed axoplasmic flow, are brought to attention. The role of
      experiment derived from clinical observation, and vice versa, is described by
      reference to a number of past and recent contributions to the understanding of
      ALS.

PMID- 11465922
TI  - Palliative care in ALS: searching for the evidence base.
AB  - The poor prognosis of amyotrophic lateral sclerosis (ALS) makes palliative care a
      challenge for the neurologist. Most of the disabilities from progressive disease
      can be effectively relieved by symptomatic treatment. Prognosis and treatment
      options should be openly discussed with patient and relatives. Adequate
      assistance and palliative treatment in the terminal phase are of paramount
      importance. Unfortunately, training in communication skills for young doctors and
      evidence-based recommendations for palliative care are insufficient at present.
      In addition, new data from a randomized study question the concept of "health
      related quality of life" and favor an individualized approach to the definition
      of quality of life in ALS.

PMID- 11465923
TI  - Genetics of sporadic ALS.
AB  - The only known gene to be involved in ALS is the CuZn-superoxide dismutase (CuZn
      SOD) gene. Since 1993, 89 disease-associated mutations have been found in this
      gene, 14 of them in cases with apparently sporadic ALS. Most frequent are the
      D90A (most often with recessive inheritance, but a few with dominant inheritance)
      and the I113T (dominant inheritance with variable penetrance). Statistical and
      genealogical evidence suggest that quite a number of diagnosed sporadic cases may
      in fact be familial cases in pedigrees with very low disease penetrance.

PMID- 11465924
TI  - Genetics of ALS in Italian families.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      affecting motor neurons. The majority of the patients are sporadic cases (SALS),
      while 10-15% of patients has a family history of ALS (familial ALS or FALS).
      Mutations in the gene coding for cytoplasmic Cu/Zn superoxide dismutase (SOD1)
      have been identified in 20% of FALS. We found SOD1-gene mutations in 7 of 36
      unrelated FALS and in 3 of 48 SALS patients. Four FALS patients carried
      previously described mutations, the A4V (2 cases), the L84F mutations (1 case),
      and the G93D (1 case), while three FALS patients carried new missense mutations:
      the G12R mutation, the F45C mutation and the V47F mutation, respectively. Two
      SALS patients carried previously reported mutations: the homozygous D90A and the
      heterozygous I113T mutation, respectively. In addition, in one SALS patient we
      identified an apparently non-pathogenic SOD1 variant: the A95T mutation. Our
      study contributes to expand the number of ALS-associated SOD1 gene mutations.

PMID- 11465925
TI  - Calcium: the Darth Vader of ALS.
AB  - Motor neuron dysfunction and loss in amyotrophic lateral sclerosis (ALS) have
      been attributed to several different mechanisms, including increased
      intracellular calcium, glutamate excitotoxicity, oxidative stress and free
      radical damage, mitochondrial dysfunction, and neurofilament aggregation and
      dysfunction of transport mechanisms. These alterations are not mutually
      exclusive, and increased calcium could be a common denominator. Furthermore, the
      selective vulnerability of spinal motor neurons and the relative sparing of eye
      motor neurons represent striking features of both sporadic and familial ALS. Here
      we review the evidence that calcium homeostasis is altered in ALS, and that low
      levels of the calcium binding proteins parvalbumin and calbindin-D28K contribute
      to selective vulnerability by decreasing the ability of motor neurons to handle
      an increased calcium load, with cell injury and death as the consequence.

PMID- 11465926
TI  - Motoneuron cell death and neurotrophic factors: basic models for development of
      new therapeutic strategies in ALS.
AB  - Motoneurons are generated in excess during embryonic development of higher
      vertebrates. In the lumbar spinal cord of the developing rat, about 6000
      motoneurons are present at embryonic day 14. These neurons grow out axons which
      make contact with their target tissue, the skeletal muscle. About 50% of the
      motoneurons are lost during a critical period from embryonic day 14 until
      postnatal day 3. This process, which is called physiological motoneuron cell
      death, has been the focus of research aiming at the identification of
      neurotrophic factors which regulate motoneuron survival during this developmental
      period. Motoneuron cell death can also be observed in vitro when the motoneurons
      are isolated from the embryonic avian or rodent spinal cord. These isolated
      motoneurons and other types of primary neurons have been a useful tool for
      studying basic mechanisms underlying neuronal degeneration during development and
      under pathophysiological conditions in neurodegenerative disorders such as
      amyotrophic lateral sclerosis (ALS). Accumulating evidence from such studies
      suggests that some specific requirements of motoneurons for survival and proper
      function may change during development. These findings might be relevant for
      understanding the pathophysiological processes underlying ALS and thus could
      contribute to the development of new therapeutic strategies.

PMID- 11465927
TI  - Human developing motor neurons as a tool to study ALS.
AB  - Defining the basis of the selective cell vulnerability of human motor neurons
      (hMNs) represents a crucial step in revealing the pathogenesis of amyotrophic
      lateral sclerosis (ALS). Tissue culture models offer an ideal system for
      identification of the hMN-specific features at the single cell level. Purified
      hMNs and astrocytes can today be isolated from the anterior horn of the human
      embryonic spinal cord. Cultures can be studied at the single cell level using
      cDNA/mRNA amplification techniques. The effects of molecules affecting hMN
      survival, neurite extension, and metabolism can be tested in vitro and the
      expression of selective genes assayed using DNA microarray technology. Crucial
      information of immediate clinical application for the treatment of patients
      affected by ALS can be derived after testing the efficacy of candidate
      pharmaceutical molecules using in vitro cell models. Adult nervous tissue or
      progenitor cells derived from different regions of the nervous system may be used
      as an alternative source of human neuronal cells. HMNs in culture, combined with
      the application of adequate technology, can contribute greatly to identifying the
      primitive critical events responsible for the cell degeneration observed in ALS,
      bypassing the intrinsic limitations of the non-human models of the disease.

PMID- 11465928
TI  - Disease status and use of ventilatory support by ALS patients. BDNF Study Group.
AB  - INTRODUCTION: Use of mechanical ventilation (MV), administered either invasively
      via tracheostomy, or more commonly non-invasively (CPAP, BiPAP), appears to be
      increasing in ALS. No prospective databases exist that describe the behavior of
      physicians and patients and the criteria for instituting MV in ALS. METHODS: 387
      placebo patients in a Phase III trial of r-metHuBDNF were followed for 9 months.
      Although the use of MV was not the primary end-point of the trial, information
      was gathered regarding it by cataloging respiratory adverse events and tracking
      health resource utilization. RESULTS: 35 of 387 patients utilized MV during the
      trial. Twenty-eight (7%) patients received BiPAP. Seven (2%) were tracheotomized
      without first receiving BiPAP. Forced vital capacity (FVC): BiPAP patients had a
      mean ( SEM) FVC% of 71.8 +/- 2.8% and ALSFRS of 27.7 +/- 1.0 at baseline; non
      BiPAP patients had a mean baseline FVC% of 88.7 +/- 1.0%, and an ALSFRS of 30.3
      +/- 0.3. Symptom duration at entry was similar for both groups (2.1 +/- 0.4 years
      vs. 2.1 +/- 0.1 years). At the time of first use of BiPAP, average FVC% was 47.5
      +/- 4.0% and ALSFRS score was 22.4 +/- 1.5. The range of FVC% at start of BiPAP
      was 15-87. The nine-month survival was 67.9% for BiPAP patients vs. 86% for non
      BiPAP patients. The use of BiPAP varied tremendously among the 38 study sites,
      with some not employing it at all and others using it in as many as 40% of
      patients. CONCLUSIONS: Of the 9% of placebo patients who received MV, BiPAP
      patients were more rapidly progressing than non-BIPAP patients, and showed a
      greater eventual mortality rate. Patients began MV at a wide range of values of
      FVC%, and centers differed in their prescribing practices. Factors influencing
      BiPAP use are complex, and not strictly related to FVC%.

PMID- 11465929
TI  - Cognitive impairment in motor neuron disease with bulbar onset.
AB  - METHODS: Twenty-three patients with bulbar onset motor neuron disease/amyotrophic
      lateral sclerosis (MND/ALS) were clinically assessed. They subsequently underwent
      serial neuropsychological testing, event-related potentials (ERP) and SPECT
      studies. Cognitive impairment was defined by clinical evidence of dementia (DSM
      IV and frontal evaluation) or by significant alteration indicated by
      neuropsychological testing (excluding patients with depression and major
      anxiety), or both. RESULTS: Eleven patients (48%) were found to be cognitively
      impaired. Abnormalities indicated fronto-temporal involvement, with memory
      impairment, alteration of judgement and reasoning, reduced speech, behavioural
      dyscontrol and alteration of daily living activities. This impairment correlated
      well with event-related potentials and SPECT studies. Event-related potentials
      were the most sensitive test as 100% of the impaired patients had abnormal ERP (p
      = 0.04). The cognitively impaired group differed from the other group mainly by
      gender ratio (male/female) with an important male predominance: 1.75 vs. 0.33.
      MND/ALS was also more severe when cognitive decline was present. CONCLUSION: This
      study adds further arguments for a cognitive impairment in MND/ALS. This also
      reinforces the hypothesis that there is continuum between MND/ALS and fronto
      temporal lobe dementia.

PMID- 11465930
TI  - Examining the evidence about treatment in ALS/MND.
AB  - The application of evidence-based medicine to the treatment of patients with
      amyotrophic lateral sclerosis (ALS) is just beginning. A small number of
      systematic reviews analyzing the pertinent evidence, grading the methodology and
      formulating recommendations to guide clinical decision-making have begun to
      appear. The American Academy of Neurology practice parameters for informing the
      patient and managing nutritional and respiratory issues and palliative care are
      discussed. In addition, the first systematic review in the field of ALS/MND from
      the Cochrane collaboration concerns riluzole treatment and this meta-analysis is
      also described. Some of the most important recommendations that have the
      potential to significantly prolong survival and enhance quality of life are the
      early institution of percutaneous endoscopic gastrostomy for patients with
      significant dysphagia, and the initiation of non-invasive positive pressure
      ventilation for patients with symptoms of early respiratory insufficiency.
      Assertive treatment of pain and dyspnea are also strongly recommended for
      patients with ALS. The North American ALS patient database, ALS C.A.R.E., is also
      described as a methodology for measuring clinical outcomes, and some early
      results are presented. The evidence on riluzole indicates effectiveness in
      prolonging survival with a good safety profile.

PMID- 11465931
TI  - Assessing health status quality of life in ALS: comparison of the SIP/ALS-19 with
      the ALS Functional Rating Scale and the Short Form-12 Health Survey.  ALS
      C.A.R.E. Study Group. Clinical Assessement, Research, and Education.
AB  - BACKGROUND: The progressive loss of function affects the quality of life of the
      ALS patient. Quality of life depends on a spectrum of factors. Available
      instruments for assessment include questionnaires developed for generic illness
      related disabilities and ALS-specific questionnaires that focus on function.
      METHODS: Comparisons were made between two ALS-specific questionnaires (ALS
      Functional Rating Scale and SIP/ALS-19) and a generic instrument (Short Form-12)
      given to 1,513 patients from the (North American) ALS Patient Care Database.
      RESULTS: The SIP/ALS-19 correlates well with the ALS Functional Rating Scale and
      less well with the Short Form-12. CONCLUSIONS: The SIP/ALS-19 can be used as an
      effective surrogate for the ALS Functional Rating Scale, with the advantage that
      the SIP/ALS-19 also includes questions that encompass the psychological and
      social domains of quality of life.

PMID- 11465932
TI  - Development, analysis, refinement, and utility of an interdisciplinary
      amyotrophic lateral sclerosis database.
AB  - The current status of evaluation and management provided by individual healthcare
      professionals (HCP) at amyotrophic lateral sclerosis (ALS) centers and clinics
      needs to be analyzed. This paper describes one ALS center's experiences with the
      development, analysis, refinement, and utility of an interdisciplinary, HCP
      driven ALS database. The purpose and conceptual framework of the database, the
      general data that needed to be collected, and the types of reports that needed to
      be generated were determined, and, in collaboration with a computer programmer,
      data entry and database management systems were developed. Data were collected on
      234 patients between September 1996 and August 1998, and were analyzed by a
      biostatistician. Based on review of the biostatistician's report and discussion
      of problems encountered with the systems, the database was then refined. Benefits
      of the database system included: systematization of data collection and
      reporting, reduction of redundant data collection by individuals, decreased
      variability of evaluation methods and management decisions from patient to
      patient, and increased availability of a variety of uniform patient information
      to assist team members in making care decisions. Ongoing refinement will ensure
      that this HCP-driven ALS database continues to be informative, practical and
      effective for decision-making and enhancing delivery of care.

PMID- 11465933
TI  - Gabapentin for the treatment of spasticity in patients with amyotrophic lateral
      sclerosis.

PMID- 11465934
TI  - MDA/ALS Clinic and Research Center at UCLA.

PMID- 11465935
TI  - ALS Center, University of Pisa, Italy.

PMID- 11465936
TI  - A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol
      (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole
      tocopherol Study Group.
AB  - INTRODUCTION: Increasing evidence suggests that oxidative stress may be involved
      in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant
      vitamin E (alpha-tocopherol) has been shown to slow down the onset and
      progression of paralysis in transgenic mice expressing a mutation in superoxide
      dismutase found in certain forms of familial ALS. The current study was designed
      to determine whether alpha-tocopherol (500 mg b.i.d.) may be efficacious in the
      treatment of ALS. METHODS: Two hundred and eighty-nine patients with ALS of less
      than 5 years duration, treated with riluzole, were enrolled in this study, and
      were randomly assigned to receive either alpha-tocopherol or placebo daily for
      one year. The primary outcome measure was the rate of deterioration of function
      assessed by the modified Norris limb scale. Patients were assessed at entry, and
      every 3 months thereafter during the study period. Survival was also recorded.
      Biochemical markers of oxidative stress were measured in a subset of patients on
      entry and after 3 months of treatment. RESULTS: After 12 months of treatment,
      alpha-tocopherol had no effect on the primary outcome measure. Survival was not
      influenced by treatment. Among secondary outcome measures, patients given alpha
      tocopherol were less likely to progress from the milder state A to the more
      severe state B (P=0.046) of the ALS Health State scale. After 3 months treatment,
      analysis of oxidative stress markers showed an increase in glutathione peroxidase
      activity in plasma (P = 0.0389) and a decrease in plasma levels of thiobarbituric
      acid reactive species (P = 0.0055) in the group of patients given alpha
      tocopherol in combination with riluzole. CONCLUSION: Although alpha-tocopherol
      did not appear to affect the survival and motor function in ALS, patients
      receiving riluzole plus alpha-tocopherol remained longer in the milder states of
      the ALS Health State scale and showed, after 3 months, changes in biochemical
      markers of oxidative stress. Further studies are required to confirm the greater
      sensitivity of the ALS Health State scale over other clinical endpoints.

PMID- 11465940
TI  - Tumor immunity and autoimmunity: a case of Dr. Jekyll and Mr. Hyde.

PMID- 11465941
TI  - Translating data from animal models into methods for preventing human autoimmune
      diabetes mellitus: caveat emptor and primum non nocere.
AB  - Type 1 diabetes in humans is a serious autoimmune disorder of children that is
      still poorly understood, unpreventable, and irreversible. Study of its animal
      models, notably the NOD mouse and BB rat, has generated a wealth of information
      concerning genetics and immunopathogenesis, but that information has still not
      altered the way in which we treat children with diabetes. In this review we
      attempt to identify the most promising avenues of continuing research in these
      models and the most important issues that must be faced by the designers of human
      therapies based on the animal dataset.

PMID- 11465942
TI  - Circulating V(alpha24+) Vbeta11+ NKT cell numbers are decreased in a wide variety
      of diseases that are characterized by autoreactive tissue damage.
AB  - Natural killer T (NKT) cells have been implicated as playing an important role in
      regulating immune responses. Defects in the NKT cell population were reported in
      animal autoimmune disease models and in distinct human autoimmune diseases. Here,
      we report that circulating V(alpha24+) Vbeta11+ NKT cell numbers are decreased in
      a broad variety of disorders with (auto)immune-mediated pathology, affecting the
      skin, bowel, central nervous system, and joints, regardless of disease duration
      or activity. Remarkably, normal circulating V(alpha24+) Vbeta11+ NKT cell numbers
      were found in Graves disease and coeliac disease. Since earlier studies noted a
      rise in NKT cells in myasthenia gravis, the picture emerges in which a defective
      NKT cell population is associated with autoreactive tissue damage rather than
      with the propensity to develop autoimmune disease. The present data support the
      idea that therapies aiming at the in vivo expansion of regulatory NKT cells might
      help to control immune-mediated damage in autoimmune disease.

PMID- 11465943
TI  - Autoimmune responses to mRNA binding proteins p62 and Koc in diverse
      malignancies.
AB  - Two tumor-associated antigens, p62 and Koc, are insulin-like growth factor II
      (IGF-II) messenger RNA binding proteins. Autoantibodies to p62 have been detected
      in cancer sera but have not been reported for Koc. This study determined the
      extent and frequency of autoantibodies to p62 and Koc in diverse malignancies,
      the epitopes on the antigens, and the presence or absence of cross-reactive
      antibodies. Recombinant polypeptides were expressed from full-length and partial
      cDNA constructs and used as antigens in Western blotting, enzyme-linked
      immunoassay, and immunoprecipitation. After identifying the epitopes, cross
      absorption with recombinant polypeptides was used to determine specificity. Sera
      from 777 patients with 10 different types of malignancy were analyzed.
      Autoantibodies to p62 were found in 11.6% and to Koc in 12.2% and cumulatively to
      both antigens in 20.5%, with significant difference from the control populations
      consisting of normal subjects and autoimmune disease patients (P < 0.01). The
      immunodominant epitopes were at the amino termini of both antigens and absorption
      studies showed that the majority of autoantibodies were not cross-reactive.
      Autoantibodies to p62 and Koc were present in approximately similar frequencies
      in a variety of malignancies and the immune responses appeared to be independent
      of each other. The immune responses might be related to overexpression or
      dysregulation of p62 and Koc in some tumors.

PMID- 11465944
TI  - The role of cpg sequences in the induction of anti-DNA antibodies.
AB  - To investigate the role of CpG sequences in anti-DNA induction, immunization
      experiments were performed in mice to assess the immunogenicity of native
      Escherichia coli (EC) and calf thymus (CT) in incomplete Freund's adjuvant. The
      effects of CpG sequences were further tested by comparing the adjuvant properties
      of a synthetic phosphorothioate oligonucleotide with a CpG motif to one with a
      GpC sequence. Both EC and CT DNA alone induced a limited anti-DNA response. For
      CT DNA, the addition of a CpG ODN significantly enhanced responses whereas for EC
      DNA, the presence of a CpG oligonucleotide (ODN) or control GpC ODN did not
      increase responses compared to EC DNA alone. Specificity analysis by ELISA
      indicated that these immunizations led to the generation of cross-reactive anti
      DNA autoantibodies. These results thus extend the adjuvant effects of CpG
      sequences to self antigens and suggest mechanisms by which self and foreign
      antigens can interact in the generation of autoimmunity.

PMID- 11465945
TI  - Immunization with DNA encoding an immunodominant peptide of insulin prevents
      diabetes in NOD mice.
AB  - DNA vaccination is an effective means of protecting experimental animals against
      infectious pathogens and cancer and has more recently been used to prevent
      autoimmune disease. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune
      disease characterized by T-cell-mediated destruction of the insulin-secreting
      beta cells in the pancreas. The NOD mouse is an animal model of IDDM in which
      several autoantigens, including insulin, have been identified. In this study we
      demonstrate that vaccination of NOD mice with DNA encoding an immunodominant
      peptide of insulin (residues 9-23 of the B chain) protects the animals from
      developing diabetes. Animals injected intramuscularly with a bacterial plasmid
      encoding the insulin B chain peptide show significantly lower disease incidence
      and delayed onset of disease when compared to controls. Protection appears to be
      mediated by insulin B (9-23)-specific down-regulation of IFN-gamma. Our results
      confirm that DNA vaccination has a protective effect on autoimmunity, the
      understanding of which will reveal new insights into the immune system and open
      doors for novel therapies.

PMID- 11465946
TI  - Pemphigus vulgaris: the role of IL-1 and IL-1 receptor antagonist in pathogenesis
      and effects of intravenous immunoglobulin on their production.
AB  - Intravenous immunoglobulin (IVIG) is increasingly being used for the treatment of
      autoimmune diseases. In the present report, the role of IVIG on in vivo and in
      vitro production of IL-1 and IL-1 receptor antagonist (Ra) was studied in
      patients with pemphigus vulgaris (PV). Serum samples from 20 untreated patients
      with active PV prior to initiation of systemic therapy, 20 patients receiving
      IVIG treatment, 20 patients in clinical remission after conventional therapy, and
      20 normal human controls were studied to determine the serum levels of IL-1alpha,
      IL-1beta, and IL-1Ra. The in vitro production of these cytokines was measured in
      the culture supernatant of peripheral blood mononuclear cells (PBMC) from 10 PV
      patients immediately before and after IVIG therapy and from age and sex-matched
      10 healthy donors simultaneously. Elevated levels of IL-1alpha and IL-1beta were
      detected (i) in the serum of untreated PV patients with active disease prior to
      systemic therapy and (ii) before IVIG infusions in patients receiving IVIG
      therapy. These increased levels are statistically significant when compared to
      the levels in healthy controls (P < 0.01). A marked reduction of IL-1alpha and IL
      1beta was detected (i) in the serum of patients in prolonged clinical remission
      and (ii) immediately after IVIG infusion in those patients on IVIG therapy.
      Increased level of IL-1Ra was detected in PV patients in prolonged clinical
      remission and after IVIG infusion in those receiving IVIG therapy. These
      differences were statistically significant when compared to the levels in normal
      controls and to the levels in the sera of patients with active disease (P < 0.01)
      or just before the beginning of IVIG infusion (P < 0.01). Similar differences in
      the levels of IL-1alpha, IL-1beta, and IL-1Ra were found in the culture
      supernatant of PBMC isolated from the PV patients pre and post IVIG therapy.
      These observations suggests that, compared to normal controls, patients with
      active PV have reversed levels of IL-1alpha, IL-1beta, and IL-1Ra. IVIG therapy
      may down-regulate production of IL-1alpha and IL-1beta and enhance production of
      IL-1Ra, in vivo and in vitro. This might be one of the important mechanisms by
      which IVIG produces its early therapeutic effects in pemphigus vulgaris.

PMID- 11465947
TI  - Long-term low-dose IL-2 enhances immune function in common variable
      immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a primary immunodeficiency disease
      characterized by hypogammaglobulinemia and lack of antibody production. Numerous
      T cell defects have been described, including reduced gene expression and
      production of IL-2. Since some of the T cell defects could be explained by lack
      of IL-2, we have been investigating the effects of in vivo IL-2 treatment. Here,
      a long-acting form of IL-2, PEG-IL-2, was given for 12-18 months to 15 randomly
      chosen CVID subjects, in comparison to 39 CVID subjects who served as controls.
      After 6 to 12 months of treatment, T cell proliferative responses to mitogens and
      to IL-2 were significantly enhanced; proliferative responses to tetanus and
      candida antigens increased up to 50-fold. Four of eight subjects immunized with
      the neoantigen bacteriophage &phi;X 174 displayed increased antibody responses
      after treatment. Treated subjects recorded reduced, but not overall statistically
      significant, days of bronchitis, diarrhea, and joint pain. These data indicate
      that IL-2 might serve as an adjuvant to therapy in some subjects with CVID,
      enhancing T cell functions and reversing T cell anergy in most.

PMID- 11465948
TI  - Antibody response to DT-GM, a novel fusion toxin consisting of a truncated
      diphtheria toxin (DT) linked to human granulocyte-macrophage colony stimulating
      factor (GM), during a phase I trial of patients with relapsed or refractory acute
      myeloid leukemia.
AB  - We are conducting a Phase I trial of a fusion toxin (DT-GM) for the treatment of
      relapsed or refractory acute myeloid leukemia (AML). The fusion toxin consists of
      a truncated diphtheria toxin (DT) linked to human granulocyte-macrophage colony
      stimulating factor (GM). Prior to beginning the Phase I trial, our first goal was
      to determine whether healthy controls and adult AML patients had preexisting
      antibodies able to inhibit DT-GM. Sera from 5 of the 9 controls completely
      neutralized DT-GM by an in vitro bioassay to assess the inhibition of DT-GM. Sera
      from 43 patients with AML were tested by bioassay and a specific
      enzymoimmunoassay (EIA) for anti-DT-GM antibodies. Forty-two of 43 samples were
      positive by EIA, and 5 patients (11.6%) showed complete neutralization of DT-GM
      in the bioassay. Anti-DT-GM concentrations were significantly higher in samples
      demonstrating neutralization than in samples demonstrating no neutralization (P =
      0.003). In the Phase I trial of DT-GM prior to therapy, none of 28 patients
      exhibited neutralization by bioassay, but 89% were positive by EIA. After the
      first course of DT-GM, 23% developed neutralizing antibodies by the bioassay, and
      64% of patients exhibited an increase in their anti-DT-GM antibody concentrations
      by EIA. Further studies are needed to determine the clinical impact of the anti
      DT-GM antibodies and whether the neutralization bioassay can be replaced by our
      EIA.

PMID- 11465949
TI  - TNF-alpha receptor 1 (p55) on islets is necessary for the expression of LIGHT on
      diabetogenic T cells.
AB  - Insulin-dependent diabetes mellitus results from T-cell-mediated destruction of
      pancreatic islet beta cells. Both CD4 and CD8 T cells have been shown to be
      independently capable of beta cell destruction. However, the mechanism of beta
      cell destruction has remained elusive. It has previously been shown that the
      absence of TNF-alpha receptor 1 (p55) on the islets protected islets from CD4 T
      cell-mediated destruction as long as the T cells did not have access to wild-type
      islets in vivo. Wild-type and TNF-alpha receptor 1 (p55) deficient islets induce
      similar levels of proliferation of BDC2.5 T cells. In this study, we demonstrate
      that islet TNF-alpha receptor 1 (p55) influences the expression of LIGHT (TNFSF
      14), a TNF family member with both cytolytic and costimulatory properties, on
      BDC2.5 T cells and the expression of its receptor HVEM (TNFRSF-14) by islets,
      indicating a role for LIGHT-HVEM interactions in autoimmune diabetes.

PMID- 11465950
TI  - Cytokines and malaria parasitemia.
AB  - The balance between pro- and antiinflammatory cytokines may be important in
      malaria presentation and outcome. Malaria tends to be more severe in children
      than in adults, presumably because partial immunity develops with age. However,
      the full nature of, and age-related differences in, anti-malarial immunity are
      unknown. We compared: (1) serum and cell-specific cytokines of patients with
      acute malaria to those of patients with other acute illnesses and to those of
      healthy adults and (2) the cytokine responses of parasitemic children and
      parasitemic adults. Flow cytometry was done on the peripheral blood mononuclear
      cells of 148 hospitalized children, 161 febrile hospitalized adults, and 20
      healthy adults in Malawi, Africa, a malaria-endemic country. Serum cytokines were
      also assessed for 80 of these patients. Thirty-eight participants were
      parasitemic with Plasmodium falciparum. Serum interleukin (IL)-10 (an
      antiinflammatory, immunoregulatory, and type 2 cytokine) levels were higher in
      malaria patients than in other patients (medians 502 pg/mL vs 16 pg/mL, P =
      0.002), and the percentages of various lymphocyte populations making IL-6 (a
      proinflammatory, type 2 cytokine regulating iron distribution) were lower in
      malaria patients than in other patients (e.g., for spontaneous production by
      children's CD8(+) T cells: medians 1.4% vs 33.1%, P = 0.004). For adult patients,
      the percentages of lymphocytes spontaneously making IL-4 (a type 2 cytokine) were
      significantly lower in those with malaria than in those without malaria (medians
      0.9% vs 2.1%, P = 0.005). The percentages of monocytes spontaneously making IL-8
      (a chemotactic, proinflammatory chemokine) were higher in parasitemic children
      than in parasitemic adults (medians 5.8% vs 1.7%, P = 0.003). A number of
      cellular proinflammatory, type 1 parameters were significantly higher in all
      children (with or without malaria) than in all adults; these included the
      percentages of various lymphocyte populations making IL-6, both IL-6 and
      interferon-gamma, or IL-8. These data support the importance of IL-10 in malaria
      parasitemia. Given the lack of an IL-4 (type 2) response, IL-10's primary role
      may be immunoregulatory rather than type 2 in nature. In this study, the immune
      response to malaria was more proinflammatory in children than in adults. This
      difference, if corroborated by other studies, could be related to malaria's
      greater severity in children.

PMID- 11465951
TI  - Simultaneous presence of mucous membrane pemphigoid and pemphigus vulgaris:
      molecular characterization of both autoantibodies.
AB  - There are several reports in the literature describing the coexistence of
      features of pemphigus vulgaris and pemphigoid in the same patient. We describe 15
      patients with clinical, histological, and immunopathological features of mucous
      membrane (cicatricial) pemphigoid at the time of initial diagnosis. All 15
      patients failed to respond clinically to conventional systemic agents over a mean
      period of 7.2 years. Hence, IVIg therapy was used. Prior to initiating IVIg
      therapy, features of mucous membrane pemphigoid and pemphigus vulgaris were
      demonstrated by various serological tests. Different assays were performed to
      identify molecular characteristics of these two autoantibodies. Twenty-five
      healthy normal individuals, 22 patients with mucous membrane pemphigoid, 17
      patients with pemphigus vulgaris, and 12 patients with pemphigus foliaceus served
      as controls for comparison of serological studies. On indirect
      immunofluorescence, using monkey esophagous as substrate, sera of all 15 patients
      had demonstrable levels of anti-intercellular cement substance (ICS) or anti
      keratinocyte cell surface antibody. Sera of 14 patients on salt split skin bound
      to the epidermal side of the split, which was consistent with mucous membrane
      pemphigoid. Sera of all 15 patients demonstrated binding to a 205-kDa protein
      (human B4 integrin) and a 130-kDa protein (desmoglein 3) on immunoblot. In a
      sample of sera from each of the 6 patients with mucous membrane pemphigoid and
      pemphigus vulgaris, the anti-ICS antibody was of the IgG4 subclass. The IgG4
      subclass is a characteristic feature associated with pathogenic autoantibodies in
      pemphigus vulgaris. Hence, in such patients, a dual diagnosis should be
      considered and confirmed by various serological assays. It is possible that the
      presence of two pathogenic autoantibodies in these patients could have
      contributed to the lack of response to conventional immunosuppressive therapy.

PMID- 11465952
TI  - T cell proliferation and cytokine secretion to T cell epitopes of Asp f 2 in ABPA
      patients.
AB  - The pathogenesis of allergic bronchopulmonary aspergillosis (ABPA) involves
      specific cytokines secreted by lymphocytes in response to Aspergillus fumigatus
      (Af) allergens. To gain information about the lymphoproliferative response and
      cytokine production against a major Af allergen, Asp f 2, we studied Asp-f-2
      specific T cell clones (TCCs) from ABPA patients. TCCs were stimulated with rAsp
      f 2, its deletion mutants, and synthetic peptides to identify the T cell
      epitope(s) and to understand cytokine production. PBMCs from four of five ABPA
      patients showed proliferation in response to Asp f 2. Three TCCs from one patient
      showed higher IL-5 secretion compared to IL-4 and IFN-gamma. Two TCCs from the
      second patient showed a mixed Th1/Th2 response, as evidenced by production of IL
      4, IL-5, and IFN-gamma. An epitope from the N-terminal region of Asp f 2 induced
      only IL-5 secretion. High IL-5 secretion might explain the marked eosinophilia
      observed in ABPA patients.

PMID- 11465953
TI  - Expression of TNFalpha by muscle fibers in biopsies from children with untreated
      juvenile dermatomyositis: association with the TNFalpha-308A allele.
AB  - Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory
      myopathy. In patients with JDM, the A --> G polymorphism in the tumor necrosis
      factor alpha (TNFalpha)-308 promoter region (TNFalpha-308A) is associated with
      prolonged disease course and increased production of TNFalpha by peripheral blood
      mononuclear cells (Arthritis Rheum. 43, 2368-2377, 2000). Magnetic resonance
      imaging directed biopsies from 21 white children with untreated JDM were
      evaluated for TNFalpha expression. Using monoclonal antibody to TNFalpha, fresh
      frozen sections were processed by the standard immunohistochemical technique. We
      investigated the association among the expression of TNFalpha by muscle fibers,
      disease activity, duration of untreated disease, and the TNFalpha-308
      polymorphism. Untreated children with JDM who had the TNFalpha-308A allele had an
      increased number of TNFalpha stained muscle fibers than children with the
      TNFalpha-308G allele (P = 0.001). There was no association with disease activity
      or duration of untreated disease. We speculate that muscle fiber production of
      TNFalpha provides a microenvironment in which TNFalpha acts synergistically with
      other mediators to prolong muscle fiber damage.

PMID- 11465954
TI  - The number and distribution of immune cells in the cervicovaginal mucosa remain
      constant throughout the menstrual cycle of rhesus macaques.
AB  - A number of studies have shown that the ovarian hormone cycle affects genital
      tract immunoglobulin (Ig) levels and T cell function in both humans and rhesus
      monkeys. We hypothesized that shifts in immune cell populations occurring in
      response to hormone cycles are involved in the observed changes in genital tract
      immunity. To test this hypothesis, we characterized the type, number, and
      distribution of immune cells in the cervicovaginal mucosa at different stages of
      the menstrual cycle. Tissues from 18 normal female rhesus macaques were studied
      by immunohistochemistry and computerized morphometric analysis. The number and
      distribution of CD1a+ Langerhans' cells, CD2+, CD3+, CD4+, and CD8+ T cells,
      CD20+ B cells, and surface Ig+ plasma cells did not change in samples collected
      at the different stages of the cycle. However, in no relation to the stage of the
      menstrual cycle, the number of Langerhans' cells and other immune cell types was
      different in the various regions of the cervicovaginal mucosa examined. In
      addition, variation in thickness of the ectocervical and vaginal epithelium
      during a normal menstrual cycle of rhesus macaques is not accompanied by changes
      in intraepithelial immune cell populations. We conclude that steroid hormones do
      not influence genital mucosal immunity by changing the number or distribution of
      immune cells in the lower reproductive tract.

PMID- 11465955
TI  - Mechanism of hypergammaglobulinemia by HIV infection: circulating memory B-cell
      reduction with plasmacytosis.
AB  - The mechanism of hypergammaglobulinemia in patients infected with HIV has
      remained unclear in spite of the identification of a reduction of CD4+ T cells.
      The amounts of CD27+ memory B cells were remarkably reduced in the peripheral
      blood and immunoglobulin (Ig) production was diminished in HIV-infected patients.
      Some of the freshly isolated patients' T cells expressed the CD70 (CD27 ligand)
      on the surface and the CD70 expression on both of the CD4+ and CD8+ T cells was
      greatly enhanced by various stimuli. It was also striking that plasmacytosis was
      observed in patients' bone marrow. Thus, our findings suggest that CD70 expressed
      spontaneously or by activation on T cells of HIV-infected patients stimulates
      memory B cells via CD27 and promotes their differentiation into plasma cells,
      resulting in the elevation of serum Ig levels and the elimination of circulating
      memory B cells in HIV-infected patients.

PMID- 11465956
TI  - The radioactive stent--any chance of a resurrection?

PMID- 11465957
TI  - The prognosis of heart failure: the view from the real world.

PMID- 11465958
TI  - Natriuretic peptides to probe haemodynamic overload in hypertrophic
      cardiomyopathy.

PMID- 11465959
TI  - Digital cellular telephones and ICDs.

PMID- 11465960
TI  - Beta-blockade and surgery.

PMID- 11465961
TI  - Guidelines on management (diagnosis and treatment) of syncope.

PMID- 11465962
TI  - The HOPE study: comparison with other trials of secondary prevention.

PMID- 11465963
TI  - The pattern of restenosis and vascular remodelling after cold-end radioactive
      stent implantation.
AB  - BACKGROUND: Edge restenosis is a major problem after radioactive stenting. The
      cold-end stent has a radioactive mid-segment (15.9 mm) and non-radioactive
      proximal and distal 5.7 mm segments. Conceptually this may negate the impact of
      negative vascular remodelling at the edge of the radiation. METHOD AND RESULTS:
      ECG-gated intravascular ultrasound with three-dimensional reconstruction was
      performed post-stent implantation and at the 6-month follow-up to assess
      restenosis within the margins of the stent and at the stent edges in 16 patients.
      Angiographic restenosis was witnessed in four patients, all in the proximal in
      stent position. By intravascular ultrasound in-stent neointimal hyperplasia, with
      a >50% stented cross-sectional area, was seen in eight patients. This was
      witnessed proximally (n=2), distally (n=2) and in both segments (n=4). Echolucent
      tissue, dubbed the 'black hole' was seen as a significant component of neointimal
      hyperplasia in six out of the eight cases of restenosis. Neointimal hyperplasia
      was inhibited in the area of radiation: Delta neointimal hyperplasia=3.72 mm3
      (8.6%); in-stent at the edges of radiation proximally and distally Delta
      neointimal hyperplasia was 7.9 mm3 (19.0%) and 11.4 mm3 (25.6%), respectively
      (P=0.017). At the stent edges there was no significant change in lumen volume.
      CONCLUSIONS: Cold-end stenting results in increased neointimal hyperplasia in in
      stent non-radioactive segments.

PMID- 11465964
TI  - The prognosis of heart failure in the general population: The Rotterdam Study.
AB  - AIMS: To determine the prognosis, cause of death, and its determinants in
      participants of the population-based Rotterdam Study who were found to have heart
      failure. METHODS AND RESULTS: In 5255 Rotterdam Study participants (aged 68.9+/
      8.6 years, 3113 women) the presence of heart failure was determined. Data were
      analysed with Cox's proportional-hazards models. One hundred and eighty-one
      participants (age 77.3+/-7.9 years, 109 women) had heart failure. Of these 85
      (47%) died during the 4.8-8.5 (mean 6.1) years of follow-up. One, 2 and 5 years'
      survival was 89%, 79%, and 59%, representing an age-adjusted mortality twice that
      of persons without heart failure (hazard ratio 2.1, 95% CI 1.8-2.7). The hazard
      ratio for sudden death was even more pronounced: 4.8, (95% CI 2.6-8.7). Diabetes
      mellitus, impairment of renal function and atrial fibrillation were associated
      with a poor outcome. A higher blood pressure and body mass index conferred a more
      favourable prognosis in those with heart failure. CONCLUSION: Heart failure
      generally afflicts older subjects in the community, carries a poor prognosis,
      especially in the presence of concomitant diseases, and confers a fivefold
      increase in the risk of sudden death.

PMID- 11465965
TI  - Determinants and clinical significance of natriuretic peptides and hypertrophic
      cardiomyopathy.
AB  - AIMS: Atrial and brain natriuretic peptide levels closely reflect impaired left
      ventricular function in patients with heart failure. In the present study we
      assessed the determinants and the clinical significance of atrial and brain
      natriuretic peptide plasma levels in hypertrophic cardiomyopathy. METHODS AND
      RESULTS: In 44 patients with hypertrophic cardiomyopathy (40+/-15 years) we
      evaluated: (a) atrial and brain natriuretic peptide plasma levels; (b) left
      ventricular hypertrophy; (c) left ventricular ejection fraction; (d) transmitral
      and pulmonary venous flow velocity patterns, and left atrial fractional
      shortening; (e) left ventricular outflow tract gradient; (f) maximal oxygen
      consumption. Left ventricular hypertrophy influenced only brain natriuretic
      peptide levels (r=0.32;P<0.05). Atrial and brain natriuretic peptide plasma
      levels did not correlate with left ventricular ejection fraction, but correlated
      with left ventricular outflow tract gradient (r=0.35;P<0.05; and r=0.40, P=0.022,
      respectively) and left atrial fractional shortening (r=-0.57;P<0.001, and r=
      0.35;P<0.05, respectively). Atrial but not brain natriuretic peptide plasma
      levels were inversely related to maximal oxygen consumption (r=-0.35;P<0.05). By
      stepwise multiple regression analysis, left atrial fractional shortening and left
      ventricular outflow tract gradient were the only predictors of atrial and brain
      natriuretic peptide plasma levels, respectively. CONCLUSIONS: In hypertrophic
      cardiomyopathy, atrial natriuretic peptide plasma levels are mainly determined by
      diastolic function: this explains the relationship with exercise tolerance. In
      contrast, brain natriuretic peptide plasma levels are mainly determined by left
      ventricular outflow tract gradient.

PMID- 11465966
TI  - In-vivo testing of digital cellular telephones in patients with implantable
      cardioverter-defibrillators.
AB  - AIMS: To investigate the susceptibility of implantable cardioverter
      defibrillators to electromagnetic interference generated by digital cellular
      telephones, functioning in both international transmission technologies: the
      Global System for Mobile Communication (GSM) and the Digital Cellular System (DCS
      1800). METHODS AND RESULTS: In 36 patients with transvenous implantable
      cardioverter defibrillators from two manufacturers (Medtronic and Guidant/CPI),
      cellular telephones with different levels of minimal and maximal power output
      were tested in the transmitting and receiving mode. Evaluation was performed in
      activated implantable defibrillators during spontaneous cardiac activity and
      continuous VVI or DDD pacing to assess possible electromagnetic interference. In
      two patients, appropriateness of ventricular fibrillation detection and therapy
      was judged during telephone testing. There was no damage, reprogramming,
      inappropriate shock therapy or pacing inhibition during the tests. In seven pre
      pectoral Medtronic implantable defibrillators, transient electromagnetic
      interference caused 19 erroneous sensing events, when the operating phone was
      held in close vicinity to the programmer head. These 'pseudo-oversensing' events,
      which did not result in logging of arrhythmia episodes in the device counter,
      were interpreted as an adverse interaction between the telephone and the
      programming device. CONCLUSION: Digital cellular telephones do not represent a
      risk to Medtronic and Guidant/CPI recipients of the specific implantable
      defibrillator models herein tested.

PMID- 11465967
TI  - Antihypertensive therapy and the risk of malignancies.
AB  - AIMS: To assess the relationship between antihypertensive therapy and malignancy.
      METHODS AND RESULTS: A MEDLINE search for English-language articles published
      between January 1966 and August 1999 identified 29 prospective studies that
      reported cancer incidence or mortality and 28 case-control studies that reported
      specific drug use in cancer patients and controls. The association between
      rauwolfia derivatives and breast cancer was analysed in 5852 cases and 9776
      controls, yielding an odds ratio (OR) of 1.25 (95% CI, 1.09-1.44). The
      association between diuretics and renal cell carcinoma was analysed in 4389 cases
      and 6566 controls, yielding a pooled OR of 1.54 (95% CI, 1.41-1.68). The
      association between atenolol and cancer death was analysed pooling three
      randomized controlled studies, including 1879 treated patients and 3078 non
      treated patients, yielding a pooled OR of 1.36 (95% CI, 1.02-1.82); however, data
      from non-randomized studies did not confirm the latter. The association between
      calcium antagonists and malignancy was analysed pooling five randomized
      controlled studies, including 5451 treated patients and 5207 untreated ones,
      yielding a pooled OR of 0.78 (CI, 0.60-1.00). A meta-analysis of an additional
      five longitudinal studies, including 9087 treated patients and 15 559 non-treated
      patients, yielded a pooled OR of 1.04 (CI, 0.91-1.19). The association between
      ACE inhibitors and malignancy was analysed pooling two randomized controlled
      trials involving 1585 treated patients and 1567 non-treated patients, yielding a
      pooled OR of 1.57 (95% CI, 0.97-2.57); however, non-randomized studies showed no
      association or a decreased risk for malignancy with ACE inhibitors. CONCLUSIONS:
      With the exception of diuretics and renal cell carcinoma, the association between
      antihypertensive drugs and malignancy was either low grade (rauwolfia), uncertain
      (atenolol), absent (ACE inhibitors), or absent with a yet to be investigated
      inverse association (calcium antagonists). Ongoing long-term prospective studies
      with cardiovascular drugs should carefully monitor the risk of malignancy.

PMID- 11465968
TI  - Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients
      as long as 2 years after successful major vascular surgery.
AB  - AIM: To assess the long-term cardioprotective effect of bisoprolol in a
      randomized high-risk population after successful major vascular surgery. High
      risk patients were defined by the presence of one or more cardiac risk factor(s)
      and a dobutamine echocardiography test positive for ischaemia. METHODS: 1351
      patients were screened prior to surgery, 846 patients had one or more risk
      factor(s), and 173 of these patients also had ischaemia during dobutamine
      echocardiography. One hundred and twelve patients could be randomized for
      additional bisoprolol therapy or standard care. Eleven patients died in the peri
      operative period (up to 1 month after surgery). Randomized patients continued
      bisoprolol or standard care after surgery. During follow-up of 101 survivors
      (median 22 months, range 11-30) cardiac death or myocardial infarction was noted.
      No patient was lost during follow-up. Results The incidence of cardiac events
      during follow-up in the bisoprolol group was 12% vs 32% in the standard care
      group (P=0.025). Cardiac death occurred in 15 patients, nine patients in the
      standard care and in six in the bisoprolol group; myocardial infarction occurred
      in six patients, five in the standard care and one in the bisoprolol group. The
      odds ratio for cardiac death or myocardial infarction after surgery in high-risk
      patients with additional bisoprolol therapy was 0.30 (0.11-0.83). CONCLUSIONS:
      Bisoprolol significantly reduced long-term cardiac death and myocardial
      infarction in high-risk patients after successful major cardiac vascular surgery.

PMID- 11465969
TI  - Comments on EMIP-FR study's editorial.

PMID- 11465970
TI  - Acute myocardial infarction in diabetic patients. Are we actually doing bad?

PMID- 11465971
TI  - Comparison of low-molecular weight heparins to unfractionated heparin.

PMID- 11465972
TI  - Atheromatosis of the aortic arch: stable and unstable plaques.

PMID- 11465976
TI  - Reliability and sensitivity measures of the Greek version of the short form of
      the McGill Pain Questionnaire.
AB  - The translation of existing healthcare measurement scales is considered a
      feasible, efficient and popular approach to produce internationally comparable
      measures. The short form of the McGill Pain Questionnaire is one of the most
      widely used and translated instruments to measure the pain experience. The Greek
      version of the short form of the McGill Pain Questionnaire (GR-SFMPQ) has
      recently been developed and demonstrated satisfactory levels of internal
      consistency. The objective of the present study was to assess the instrument's
      reliability and sensitivity.Eighty patients with spinal or knee pain were
      included. The test-retest reliability of the instrument was estimated for
      measurements within the same day and after 15 days. The sensitivity of the
      measure was examined before and after the application of a physiotherapy
      therapeutic regime. The correlation coefficients (Intraclass Correlation
      Coefficient and Spearman's) ranged from 0.87-0.98 for within-day measurements and
      from 0.70-0.92 for administrations between days. All indexes of the GR-SFMPQ
      (total score, sensory and affective scores, total count of used words, visual
      analogue score, present pain index) managed consistently to detect the changes in
      pain experienced (p<0.05), after a therapeutic intervention, when assessing for
      the sensitivity of the questionnaire. An explorative discriminant analysis of the
      GR-SFMPQ indexes managed to correctly classify up to 85% of the patients; a
      classification rate comparable to the full version MPQ rating capacity. It can be
      argued from the results of this study that the Greek version of the SFMPQ fulfils
      the criteria of reliability and sensitivity to fluctuations of pain and can be
      utilized with confidence in cross-cultural comparative research trials.

PMID- 11465977
TI  - Pregabalin in patients with postoperative dental pain.
AB  - Pregabalin is an analogue of the inhibitory neurotransmitter gamma-aminobutyric
      acid. In preclinical models, it has shown activity as an analgesic agent. A
      randomized, double-blind, placebo-controlled, parallel-group trial was undertaken
      to compare pregabalin to placebo and 400 mg of ibuprofen using a dental pain
      model. Study medication was administered postoperatively to patients who had
      undergone elective surgery to remove one or two third molars, at least one of
      which was mandibular and fully or partially impacted in bone. The study was
      conducted in the UK at a single centre and evaluated pregabalin at doses of 50
      and 300 mg. Primary efficacy parameters included pain relief (PR), pain intensity
      difference (PID), pain relief intensity difference (PRID), time to onset of
      analgesia, and duration of analgesia. The patient's global impression of the
      study medication was used as a secondary efficacy parameter. Efficacy data were
      evaluated for the intent-to-treat (ITT) population, defined as all randomized
      patients who took study medication. Results showed that there were statistically
      significant differences in PR, PID, and PRID between the 300-mg pregabalin group
      and placebo. In addition, the 300-mg pregabalin group had a significantly longer
      duration of analgesia than the ibuprofen group and had the highest score on the
      patient global impression of study medication. Adverse events were reported more
      frequently in the pregabalin 300-mg group. Pregabalin appears to have significant
      analgesic properties in the third molar extraction model. Further research is
      needed to confirm these findings.

PMID- 11465978
TI  - Influence of expectations and actual pain experiences on satisfaction with
      postoperative pain management.
AB  - Experience of moderate or even severe postoperative pain has remained a clinical
      problem despite major progress in pain assessment and management. The aim of the
      present study was to assess any association between different pre- as well as
      postoperative factors, actual pain experiences in the postoperative period, and
      the overall patient satisfaction with the pain management. A random sample of
      surgical patients (n =191) responded to pre- and postoperative questionnaires
      detailing presence of preoperative baseline pain, expected and actually
      experienced postoperative pain levels and perceived adequacy of the pain relief
      provided. Patient satisfaction was assessed and factors of importance for
      satisfaction/dissatisfaction were analysed. It was found that 88% of the patients
      had previously undergone surgical procedures and that 53% of these patients
      claimed to have experienced moderate or severe pain at that time. Current pain
      prior to the present surgical procedure was reported by 61% of the patients. Most
      patients (91%) expected pain of moderate to severe intensity and 76% reported to
      have experienced such pain levels. In spite of this 81% of the patients claimed
      to be satisfied with the pain management while only 8% were dissatisfied. Sex,
      age, pre-operative expectation and actual experience of pain relief, and the
      overall pain experience were found to be factors associated with the probability
      of being satisfied/dissatisfied. Main characteristics of the dissatisfied patient
      were a younger age and female sex. It is concluded that patients commonly expect
      moderate to severe pain in the postoperative period and that the actual pain
      experience is mainly in accordance with the pre-operative expectations.
      Therefore, the validity of patient satisfaction as an optimal outcome variable in
      quality assurance processes of postoperative pain management may be questioned.

PMID- 11465979
TI  - Sensory changes during the ovulatory phase of the menstrual cycle in healthy
      women.
AB  - This study compared the pain sensitivity in healthy women at the abdomen and
      lower back (presumed referral areas of menstrual pain), thigh and arm (control
      areas), in the menstrual, ovulatory, luteal and premenstrual phases of confirmed
      ovulatory cycles, with that of males. The pressure pain threshold (PPT) and pinch
      pain threshold (PiPT) was determined by an electronic pressure algometer, heat
      pain threshold (HPT) by a contact thermode and tactile threshold (TT) with von
      Frey hairs. The abdominal PPT was significantly lower in females in all menstrual
      phases as compared to the control sites ( p<0.0007). The abdominal and lower back
      HPT was significantly lower in females in all menstrual phases compared with
      control areas, and to the sites in males ( p<0.002). The TT was significantly
      reduced in females compared with males ( p< 0.013). There was no difference in
      the PiPT between females and males. In males, the HPT, PPT and TT were not
      different within any site. During the ovulatory phase, the HPT was significantly
      reduced at the abdomen and the PPT at the back compared with the menstrual,
      luteal and premenstrual phases (p<0.0002). There were no within-menstrual phase
      variations in the PiPT and TT at any site, or for the HPT and PPT at the control
      areas. The reduced thresholds in menstruating women may be due to the presence of
      latent uterine algogenic stimuli, and the increased levels of oestrogen and
      leuteinizing hormone at ovulation may enhance nociception by acting both at the
      peripheral and central level, resulting in the hypersensitivity changes at the
      abdomen and lower back areas.

PMID- 11465980
TI  - Prevalence and characteristics of headache in Dutch schoolchildren.
AB  - The aim of this study was to determine whether there has been an increase in
      headache prevalence in Dutch children and to compare headache characteristics of
      children with low, medium and high headache severity.A sample of 2358
      schoolchildren between the ages of 10 and 17 years filled out Waters' Headache
      Questionnaire and the Paediatric Pain Assessment Tool. Results showed that 21% of
      the boys and 26% of the girls at elementary school, and 14% of the boys and 28%
      of the girls at high school reported weekly headaches. When compared to figures
      from a previous study in the Netherlands published in 1985, the prevalence of
      weekly headaches in 10-17-year-olds has increased by 6%. In boys at elementary
      school, the prevalence of headaches with a frequency of a few times a week has
      doubled. Children with low, medium and high headache severity differed with
      respect to all headache characteristics, i.e. pain quality, accompanying
      symptoms, warning signals, location, onset, impact of headache, family
      occurrence, perceived cause, medical consultation, and school absence.

PMID- 11465981
TI  - Differential time courses of skin blood flow and hyperalgesia in the human
      sunburn reaction following ultraviolet irradiation of the skin.
AB  - The response of skin to ultraviolet (UV) irradiation is an inflammation with
      pronounced vasodilation and hyperalgesia. Volunteers underwent UV irradiation of
      patches of forearm skin 3 cm in diameter. The intensity of the UV irradiation
      (290-320 nm) ranged between 133 mJ/cm2 and 400 mJ/cm2. Changes in skin blood flow
      were measured with laser Doppler technique at 3, 6, 9, 12, 24, 30, 36, 48, 60,
      72, 96 and 216 h post UV irradiation. The alteration in pain threshold was
      measured for heat with a Peltier thermode and for pressure with a metal stylus.
      The effect of repeated topical pre-treatment 4 days prior to UV irradiation with
      1.5 g of 0.04% capsaicin containing ointment was also investigated.UV irradiation
      resulted in a dose-dependent increase of skin blood flow for more than 96 h post
      irradiation. There were two peaks of blood flow at 12 h and 36 h. Topical
      application of capsaicin prior to UV irradiation attenuated blood flow from 30 h
      to 45 h post UV irradiation. Enhanced blood flow was also present 5 mm outside
      the irradiated area (flare reaction). The control level of heat pain threshold
      was 44.5+/-0.7;C in normal skin. Heat pain thresholds were lowered by up to
      7.761.2;C in UV-irradiated areas in a dose-dependent fashion. The control level
      of pressure pain threshold was 15.260.3N. Pressure pain thresholds were lowered
      by up to 6 N in irradiated areas. Maximal hyperalgesia coincided with the second
      peak of skin blood flow between 30 h and 60 h post UV irradiation. The effects of
      topical application of capsaicin suggests an involvement of neuropeptide
      mechanisms in the late phase of the human sunburn reaction.

PMID- 11465982
TI  - The morphological effects of a radio frequency lesion adjacent to the dorsal root
      ganglion (RF-DRG)--an experimental study in the goat.
AB  - Radiofrequency (RF) lesions adjacent to the dorsal root ganglion (DRG) are
      increasingly used in the treatment of intractable chronic pain of spinal origin.
      Opinions differ on which nerve fibres are affected by these lesions.
      Morphological studies have been carried out to assess the effects of
      radiofrequency lesions on nervous tissue. Interpretation has been difficult,
      since most studies have been performed under circumstances which are not
      comparable to the clinical situation. This study was undertaken to investigate
      morphological effects of RF lesions as they develop in the normal clinical
      situation. In two goats 22 G 100 mm SMK electrodes with a 5 mm active tip
      (Radionics) were positioned posterior to the lumber dorsal root ganglia (DRG).
      Sixty-second 67;C lesions were made on one side. The contralateral side was used
      as sham operation. The goats were sacrificed 2 weeks after the procedure. The
      lesions were studied for size as well as for effects on proliferation and
      regeneration using Ki-67 (MIB-1). Lesions made inside the DRG (23) were 1.8-2.0
      mm in size. In these lesions there was a total loss of myelinated fibres. In
      lesions made adjacent to the DRG there was a significantly higher MIB-1 labelling
      on the treated side as compared to the sham-treated side. An RF lesion inside the
      DRG destroys myelinated fibres. A lesion adjacent to the DRG increases MIB-1
      activity, indicating proliferation and regeneration after 2 weeks, despite the
      fact that the lesion was made outside the ganglion.

PMID- 11465983
TI  - The spatial organization of central sensitization of hind limb flexor reflexes in
      the decerebrated, spinalized rabbit.
AB  - This study was designed to investigate the relationship between the location of a
      noxious stimulus and the magnitude and duration of the plastic effects induced by
      that stimulus in withdrawal reflexes acting about the knee and the ankle, in
      rabbits. Reflexes were evoked in the nerves to the anterior tibial and
      semitendinosus flexor muscles by electrical stimulation at the toes. Repetitive,
      high intensity electrical stimulation of nerve trunks (sural, medial
      gastrocnemius, superficial peroneal, tibial, 100 pulses, 20 V, 1 ms at 0.5 Hz)
      was generally found to be a poor method for inducing central sensitization in
      these flexor reflexes. 'Natural' noxious stimulation induced more reliable
      enhancement of both reflexes. Mechanical (clamp) or chemical (mustard oil)
      stimulation of the heel induced prolonged (median duration >30 min) increases in
      reflexes to both muscles. Mechanical (clamp and superficial pinch) or chemical
      (mustard oil) stimulation of the toes, and injection of bradykinin into the
      gastrocnemius muscles or into the soft tissues of the sole of the foot, also led
      to enhancement of both reflexes, with the median duration of potentiation between
      7 and 30 min. The effects obtained from deep tissue stimulation were generally
      weaker than those obtained after stimulation of superficial structures. These
      data show that there were no major differences in the effects obtained from the
      heel vs the toes, or between the two reflexes. It appears that the spatial
      organization of the spinal mechanisms underlying central sensitization of flexor
      withdrawal reflexes is rather more crudely drawn than that pertaining to the
      reflexes themselves. Furthermore, the data indicate that in the present
      preparation, afferents from deep tissues are no more effective in generating
      central sensitization than those from superficial structures.

PMID- 11465984
TI  - Cross-validation of the SCL-27: a short psychometric screening instrument for
      chronic pain patients.
AB  - We constructed a short multidimensional screening instrument for chronic pain
      patients based on the items contained in the Symptom Check List-90-Revised (SCL
      90-R). The proposed dimensional structure of the SCL-90-R was recently shown to
      be irreproducible in chronic pain patients. As a consequence, the use of the
      Global Severity Index (GSI) was recommended, although it did not capture all
      information contained in the many items of the SCL-90-R. Based on an exploratory
      factor analysis, a six-dimensional structure using 27 items from the SCL-90-R was
      explored utilizing the data of 2780 chronic pain patients. A short form was
      prospectively tested on 581 patients in the same setting. Criteria for item
      selection were high convergent and low discriminant correlations. The assessment
      of the dimensions was kept short, but a minimum of four items were retained. A
      questionnaire yielding the dimensions (I) depressive symptoms, (II) dysthymic
      symptoms, (III) vegetative symptoms, (IV) agoraphobic symptoms, (V) symptoms of
      social phobia, and (VI) symptoms of mistrust was obtained. Additionally, the GSI
      of the SCL-90-R could be estimated precisely (r =0.96). The SCL-27 can be used
      for screening psychopathology in chronic pain patients. The scoring algorithm of
      the SCL-27 can be used for the 90-item form as well.

PMID- 11465985
TI  - Systemic adenosine infusion reduces the area of tactile allodynia in neuropathic
      pain following peripheral nerve injury: a multi-centre, placebo-controlled study.
AB  - Systemic adenosine has been shown in earlier case reports and a small placebo
      controlled study to reduce pathological sensory dysfunction such as tactile
      allodynia in neuropathic pain. To evaluate this further, the effects of systemic
      adenosine infusion (50 microg/kg/min for 60 min) on tactile sensory dysfunction
      and pain was evaluated in 26 patients suffering peripheral neuropathic pain
      characterized by dynamic tactile allodynia. A randomized, cross-over, double
      blind, placebo-controlled technique was used in this multi-centre study.
      Psychophysical methods were used to evaluate sensory dysfunction and spontaneous
      pain. The area of dynamic tactile allodynia was significantly reduced by
      adenosine compared with placebo (p=0.043), but spontaneous pain and tactile pain
      threshold were not significantly improved compared with the effects of placebo
      treatment. As a secondary outcome, a higher incidence of positive subjective
      effects on the clinical pain condition, in a few cases with long duration
      (several months), following adenosine treatment was found when the global effect
      of respective treatment was assessed (p=0.028). The results demonstrate
      involvement of adenosine receptor-sensitive pain mechanisms in some aspects of
      the sensory dysfunction often found in neuropathic pain.

PMID- 11465986
TI  - Central pain in a hemispherectomized patient.
AB  - We have examined a hemispherectomized patient who complained of touch-evoked
      pricking and burning pain in her paretic hand, especially when the hand was cold.
      Psychophysical examination showed that for the paretic side she confused cool and
      warm temperatures, and confirmed that she had a robust allodynia to brush
      stroking that was enhanced at a cold ambient temperature. Functional magnetic
      resonance imaging (fMRI) showed that during brush-evoked allodynia, brain
      structures implicated in normal pain processing (viz. posterior part of the
      anterior cingulate cortex, secondary somatosensory cortex, and prefrontal
      cortices) were activated. The fMRI findings thus indicate that the central pain
      in this patient was served by brain structures implicated in normal pain
      processing. Possible pathophysiological mechanisms include plasticity as well as
      thalamic disinhibition.

PMID- 11465987
TI  - Nalbuphine by PCA-pump for analgesia following hysterectomy: bolus application
      versus continuous infusion with bolus application.
AB  - The analgesic properties of the partial agonist-antagonist nalbuphine in the
      postoperative period are well known. When used for patient-controlled analgesia
      (PCA) the effectiveness of this substance is comparable to that of morphine or
      tramadol. However, the optimal programme for administration of nalbuphine in PCA
      pumps has not been investigated. In particular, the combination of bolus
      administration vs bolus administration plus continuous basal administration is
      disputable. We hypothesized that the administration of an extra basal rate of
      nalbuphine in addition to the patient- triggered bolus administration and
      supplemental doses of diclofenac when required, would lead to a significant
      improvement in analgesia, without affecting the differences in vital signs and
      side effects. After approvement by the institutional ethics committee, 50 female
      patients (ASA I or II) scheduled for elective hysterectomy were included in a
      prospective, single-blinded study and randomized either into bolus-continuous (BC
      )group (3 mg base rate/h, 1 mg bolus, 20 min lock out) or bolus (B-)group (no
      base rate, 1 mg bolus, 10 min lock out). During the observation period (up to 24
      h postoperative) vital parameters, extent of analgesia (10-step VAS), and
      vigilance (5-step scale) were registered. Groups were compared by using unpaired
      Student t-test. A p<0.05 was considered to be significant. No differences were
      found in demographic data or vital parameters (MAP, PaO2, PaCO2, respiratory
      rate, heart rate, peripheral SaO2) during the observation period. Vital
      parameters showed no pathological changes in any group. With an identical rate of
      requirement for diclofenac (32 and 36%), analgesia in BC-group showed a decrease
      in VAS from 4.28+/-2.11 to 2.04+/-1.21 and from 3.64+/-2.20 to 2.08+/-0.96 in B
      group. Vigilance was only marginally diminished in both groups. No serious side
      effects were found in either group. The consumption of nalbuphine (mg) was
      significantly higher in BC-group (70.28+/-13.85 vs. 47.44+/-22.99;p =0.0002) when
      compared to B-group. Subjective rating of effectiveness by the patients was
      similar in both groups. The two administration settings of nalbuphine by PCA pump
      have shown to be equally effective in the treatment of postoperative pain
      following hysterectomy. However, as the total amount of nalbuphine was
      significantly lower in B-group, the use of this administration schedule should be
      encouraged.

PMID- 11465988
TI  - Five easy pieces on evidence-based medicine (3).

PMID- 11465989
TI  - Plasmodium falciparum: gene mutations and amplification of dihydrofolate
      reductase genes in parasites grown in vitro in presence of pyrimethamine.
AB  - Samples of three pyrimethamine-sensitive clones of Plasmodium falciparum were
      grown for periods of 22-46 weeks in media containing stepwise increases in
      pyrimethamine concentrations and were seen to develop up to 1000-fold increases
      in resistance to the drug. With clone T9/94RC17, the dihydrofolate reductase
      (DHFR) gene was sequenced from 10 uncloned populations and 29 pure clones, all
      having increased resistance to pyrimethamine, and these sequences were compared
      with the sequence of the original pyrimethamine-sensitive clone. No changes in
      amino acid sequence were found to have occurred. Some resistant clones obtained
      by this method were then examined by pulsed-field gel electrophoresis, and the
      results indicated that there had been an increase in the size of chromosome 4.
      This was confirmed by hybridization of Southern blots with a chromosome 4
      specific probe, the vacuolar ATPase subunit B gene, and a probe to DHFR. Dot
      blotting with an oligonucleotide probe to DHFR confirmed that there had been
      increases up to 44-fold in copy number of the DHFR gene in the resistant strains.
      Resistant clones obtained by this procedure were then grown in medium lacking
      pyrimethamine for a period of nearly 2 years, and reversion nearly to the level
      of pyrimethamine sensitivity of the original clone T9/94RC17 was found to occur
      after about 16 months. Correspondingly, the chromosome 4 of the reverted
      population reverted to a size like that of the original sensitive clone
      T9/94RC17. The procedure of growing parasites in stepwise increases of
      pyrimethamine concentration was repeated with two other pyrimethamine-sensitive
      clones: TM4CB8-2.2.3 and G112CB1.1. (The DHFR gene of these clones encodes serine
      at position 108, in place of threonine as in clone T9/94RC17, and it was thought
      that this difference might conceivably affect the rate of mutation to asparagine
      at this position). Clones TM4CB8-2.2.3 and G112CB1.1 also responded by developing
      gradually increased resistance to pyrimethamine. However, in clone TM4CB8-2.2.3 a
      single mutation from Ile to Met at position 164 in the DHFR gene sequence was
      identified, and in clone G112CB1.1 there was a single mutation from Ala to Ser at
      position 16, but no mutations at position 108 were obtained in any of the clones
      studied here. In addition, chromosome 4 of clone TM4CB8-2.2.3 increased in size,
      presumably due to amplification of the DHFR gene. No increase in size was seen in
      clone G112CB1.1. We conclude that whereas some mutations producing changes in the
      amino acid sequence of the DHFR molecule may occur occasionally in clones or
      populations of P. falciparum grown in vitro in the presence of pyrimethamine,
      amplification of the DHFR gene following adaptation to growth in medium
      containing pyrimethamine occurs as a regular feature. The bearing of these
      findings on the development of pyrimethamine-resistant forms of malaria parasites
      in endemic areas is discussed.

PMID- 11465990
TI  - Plasmodium chabaudi chabaudi: B-1 cell expansion correlates with semiresistance
      in BALB/cJ mice.
AB  - The largest obstacle impeding the development of an effective malaria vaccine is
      the incomplete understanding of how the immune response is regulated during
      infection. B-1a cells, a poorly understood subcategory of B lymphocytes, produce
      nonpathologic autoantibodies of low affinity which have been shown to have
      distinct immunoregulatory capabilities. What the exact activity of B-1a cells are
      during the course of malaria has yet to be determined. By use of flow cytometry,
      it was observed that B-1a cells significantly expand by day 3 postinfection in
      the spleen and peritoneum of Plasmodium chabaudi chabaudi semiresistant BALB/cJ
      mice, but not until day 8 postinfection in the spleen of P. chabaudi chabaudi
      fully susceptible BALB/cByJ mice. The activation of B-1a cells was also
      demonstrated by the measurement of natural autoantibody IgM production from the
      serum and cultured peritoneal B-1a cells. Infected semiresistant BALB/cJ mice
      generated higher levels of anti-ssDNA IgM antibodies than infected fully
      susceptible BALB/cByJ mice. The preliminary data presented here suggest a
      possible roll of B-1 cells in contributing to the successful survival of murine
      malarial infection.

PMID- 11465991
TI  - Entamoeba histolytica: monoclonal antibody against the beta1 integrin-like
      molecule (140 kDa) inhibits cell adhesion to extracellular matrix components.
AB  - We describe a monoclonal antibody (3C10) against the beta1 integrin-like molecule
      which immunoprecipitates two polypeptides of 140 and 155 kDa from detergent
      soluble extract of Entamoeba histolytica. The 140-kDa polypeptide has been
      described as a beta subunit of the amoebic fibronectin receptor as it is
      recognized by an anti-integrin beta1 (human) monoclonal antibody in immunoblot
      assay. The receptor molecules were localized with the 3C10 monoclonal antibody in
      intracellular and surface membranes of E. histolytica trophozoites by
      immunofluorescence and immunogold labeling methods. Significant inhibitions of
      cell adhesion on extracellular matrix proteins such as fibronectin (56%) (P <
      0.001) and collagen (50%) (P < 0.001) and partial inhibition on laminin (23%) (P
      > 0.1) were achieved by the monoclonal antibody.

PMID- 11465992
TI  - Molecular analyses of Old World Leishmania RAPD markers and development of a PCR
      assay selective for parasites of the L. donovani species Complex.
AB  - Three amplicons, appearing in a species-specific manner on the electrophoregrams
      of RAPD reactions that were obtained with primer OPA1, OPA1-800, OPA1- 900, and
      OPA1-1200, are analyzed in this study. The study revealed that each of these
      products is composed of one Leishmania DNA band, taxonomically conserved among
      the different Old World species studied. Subsequently, only the electrophoretic
      position of the RAPD products can be considered species-specific. In addition,
      sequence data, genomic organization, and chromosomal location have proved that
      these fragments are different and physically independent. However, they possess
      common features related to the presence of different kinds of short DNA repeats,
      more particularly microsatellites and a CCCTTC motive, corresponding to the 3'
      half of the OPA1 primer. These results suggest that the OPA1 primer has initiated
      amplification from different priming sites, having a species-specific location.
      This corresponds to sequence micro-heterogeneity of DNA fragments present within
      the different species and leading eventually to a selective amplification of
      different RAPD products. This characteristic has been used to develop an original
      selective PCR test based on the sequence of the OPA1-800 product, in which only
      DNAs from the L. donovani species complex are amplified. Restriction site
      polymorphisms and sequence variations are identified within the PCR fragment
      amplified from these parasite DNAs. In fact, the OPA1-800 fragment proved to be a
      useful DNA marker either as a DNA probe or as a target for PCR-based assays. This
      tool can therefore be recommended for the control of Old World Leishmania
      parasites, such as species discrimination, molecular tracking of isolates, or
      study of polymorphisms within the L. donovani species complex. Moreover, the
      molecular bases underlying the amplification of the RAPD fragments studied
      correspond to mechanisms already described. Although they do not account for the
      amplification of all Leishmania RAPD products, such mechanisms stress some of the
      pitfalls of the technique, which need to be taken into consideration. We have
      identified at least misleading observations of DNA bands amplified in a species
      specific manner, in spite of their presence in the genome of the other taxa, and
      relatedness between bands within the amplification profiles. Therefore,
      recommendations for careful interpretation of RAPD data in population genetics or
      phylogenetic analyses are reiterated. Molecular analyses are essential to
      validate conclusions.

PMID- 11465993
TI  - O-glycosylation in Echinococcus granulosus: identification and characterization
      of the carcinoma-associated Tn antigen.
AB  - In the present work we demonstrate that the cancer-associated O-glycosylated Tn
      antigen (GalNAc-O-Ser/Thr) is expressed by the cestode Echinococcus granulosus.
      This antigen was detected in both larval and adult worm extracts, with the
      highest specific activity observed in the adult excretion/secretion preparation.
      Histochemical analysis showed that Tn is preferentially expressed in the
      parenchyma in both parasite stages and the external part of tegument in adult
      worms. A similar pattern was observed for sialyl-Tn, a related O-linked antigen.
      Tn glycoproteins from protoscoleces were resolved by SDS-PAGE in two main
      components of 43 and 49 kDa. After purification, this material was reactive with
      lectins which bind GlcNAc/sialic acid, GalNAc, and T antigen. In a preliminary
      evaluation, high levels of Tn antigen were detected in serum samples from
      patients with hydatid cyst, suggesting that the measure of Tn in serum could be a
      biomarker of this disease, although extensive work is necessary in order to
      determine the clinical usefulness of this assay. The results reported here, the
      first evidence of O-glycosylation pathways in E. granulosus and the presence of
      Tn antigen in cestodes, suggest that the evaluation of O-glycosylated antigens
      might give new insights in the host-parasite relationship.

PMID- 11465994
TI  - Plasmodium falciparum: the lethal effects of tunicamycin and mevastatin on the
      parasite are not mediated by the inhibition of N-linked oligosaccharide
      biosynthesis.

PMID- 11465996
TI  - Use of fractal theory in neuroscience: methods, advantages, and potential
      problems.
AB  - Fractal analysis has already found widespread application in the field of
      neuroscience and is being used in many other areas. Applications are many and
      include ion channel kinetics of biological membranes and classification of
      neurons according to their branching characteristics. In this article we review
      some practical methods that are now available to allow the determination of the
      complexity and scaling relationships of anatomical and physiological patterns.
      The problems of describing fractal dimensions are discussed and the concept of
      fractal dimensionality is introduced. Several related methodological
      considerations, such as preparation of the image and estimation of the fractal
      dimensions from the data points, as well as the advantages and problems of
      fractal geometric analysis, are discussed.

PMID- 11465997
TI  - The effect of type 1 astrocytes on neuronal complexity: a fractal analysis.
AB  - Embryonic, ventral spinal cord neurons were grown on poly(d-lysine) (PDL) or on a
      monolayer of type 1 astrocytes. At various times from 6 h to 2 weeks postplating,
      cells were fluorescently labeled and fixed with 4% paraformaldehyde. The cell
      surface immunoreaction allowed visualization of neurons in their entirety,
      namely, cell bodies and various membranous extensions that included lamellipodia,
      growth cones, axons, and dendrites. Outlines were drawn for individual neurons
      and their fractal dimension (D) was calculated. Neurons on poly(d-lysine) reached
      a peak D at 3 days in vitro, 1 day later than neurons on astrocytes (2 days in
      vitro). The maximum D was greater for cells on poly(d-lysine) when compared with
      neurons on astrocytes. In a second experiment the maximum D was similar for
      neurons on both surfaces but neurons on PDL maintained a higher D for a much
      longer period than neurons on astrocytes. An examination of fluorescent images
      revealed that neurons on poly(d-lysine) exhibited lamellipodia and large growth
      cones for several days and these structures were likely responsible for the high
      D seen in these cells. These structures were rarely observed in neurons plated on
      astrocytes. Interestingly, D on both surfaces decreased to a similar value at
      between 1 and 2 weeks in vitro. The trend for D in these cultures, an initial
      increase to a peak value followed by a decrease to a stable value, is discussed
      in light of the chemical nature of the two surfaces and synapse formation and
      stabilization.

PMID- 11465998
TI  - Analysis of fractal dimension of O2A glial cells differentiating in vitro.
AB  - Fractal dimension is a quantitative measure of morphological complexity. Glial
      cells of the oligodendrocyte-type 2 astrocyte (O2A) lineage exhibit increasing
      morphological complexity as they differentiate in vitro. Enriched populations of
      O2A progenitor cells isolated from neonatal rat cerebral hemispheres or optic
      nerves were allowed to differentiate in vitro, and their fractal dimensions were
      measured over time. The fractal dimensions of the maturing cells correlated with
      perceived complexity; cells with elaborate process branching had larger fractal
      dimensions than cells with a simpler morphology. An analysis of changes in
      fractal dimension revealed distinct rates of growth for both oligodendrocytes and
      type 2 astrocytes. The fractal dimension remained constant over a 10-fold range
      in optical magnification, demonstrating that cultured O2A glial cells exhibit
      self-similarity, a defining characteristic of fractal objects. These results
      illustrate that fractal dimension analysis of maturing cell populations is a
      useful method for quantitatively describing the process of cell differentiation.

PMID- 11465999
TI  - A single-cell model to study changes in neuronal fractal dimension.
AB  - Many methods have been developed to quantify neuronal morphology: measurement of
      neurite length, neurite number, etc. However, none of these approaches provides a
      comprehensive view of the complexity of neuronal morphology. In this work we have
      analyzed the evaluation of fractal dimension (D) as a tool to represent and
      quantify changes in complexity of the dendritic arbor, in in vitro cultures grown
      under low-density conditions. Neurons grown in isolation developed a bipolar
      morphology corresponding to a fractal dimension close to the unit. The analysis
      showed that neuronal complexity increased when cells were incubated with a
      depolarizing potassium concentration and there was a correlation with an increase
      in fractal dimension (D5 mM KCl = 1.08 +/- 0.01, D25 mM KCl =1.25 +/- 0.01). We
      conclude that fractal dimension is a suitable parameter to quantify changes in
      neuronal morphological complexity.

PMID- 11466000
TI  - Wavelet packet fractal analysis of neuronal morphology.
AB  - An image analysis method called two-dimensional wavelet packet analysis (2D WPA)
      is introduced to quantify branching complexity of neurons. Both binary
      silhouettes and contour profiles of neurons were analyzed to determine accuracy
      and precision of the fractal dimension in cell classification tasks. Two
      dimensional WPA plotted the slope of decay for a sorted list of discrete wavelet
      packet coefficients belonging to the adapted wavelet best basis to obtain the
      fractal dimension for test images and binary representations of neurons. Two
      dimensional WPA was compared with box counting and mass-radius algorithms. The
      results for 2D WPA showed that it could differentiate between neural branching
      complexity in cells of different type in agreement with accepted methods. The
      importance of the 2D WPA method is that it performs multiresolution decomposition
      in the horizontal, vertical, and diagonal orientations.

PMID- 11466001
TI  - Fractal methods to analyze ion channel kinetics.
AB  - We describe the traditional nonfractal and the new fractal methods used to
      analyze the currents through ion channels in the cell membrane. We discuss the
      hidden assumptions used in these methods and how those assumptions lead to
      different interpretations of the same experimental data. The nonfractal methods
      assumed that channel proteins have a small number of discrete states separated by
      fixed energy barriers. The goal was to determine the parameters of the kinetic
      diagram, which are the number of states, the pathways between them, and the
      kinetic rate constants of those pathways. The discovery that these data have
      fractal characteristics suggested that fractal approaches might provide more
      appropriate tools to analyze and interpret these data. The fractal methods
      determine the characteristics of the data over a broad range of time scales and
      how those characteristics depend on the time scale at which they are measured.
      This is done by using a multiscale method to accurately determine the probability
      density function over many time scales and by determining how the effective
      kinetic rate constant, the probability of switching states, depends on the
      effective time scale at which it is measured. These fractal methods have led to
      new information about the physical properties of channel proteins in terms of the
      number of conformational substates, the distribution of energy barriers between
      those states, and how those energy barriers change with time. The new methods
      developed from the fractal paradigm shifted the analysis of channel data from
      determining the parameters of a kinetic diagram to determining the physical
      properties of channel proteins in terms of the distribution of energy barriers
      and/or their time dependence.

PMID- 11466002
TI  - Fractal features of dark, maintained, and driven neural discharges in the cat
      visual system.
AB  - We employ a number of statistical measures to characterize neural discharge
      activity in cat retinal ganglion cells (RGCs) and in their target lateral
      geniculate nucleus (LGN) neurons under various stimulus conditions, and we
      develop a new measure to examine correlations in fractal activity between spike
      train pairs. In the absence of stimulation (i.e., in the dark), RGC and LGN
      discharges exhibit similar properties. The presentation of a constant, uniform
      luminance to the eye reduces the fractal fluctuations in the RGC maintained
      discharge but enhances them in the target LGN discharge, so that neural
      activities in the pair cease to be mirror images of each other. A drifting
      grating stimulus yields RGC and LGN driven spike trains similar in character to
      those observed in the maintained discharge, with two notable distinctions: action
      potentials are reorganized along the time axis so that they occur only during
      certain phases of the stimulus waveform, and fractal activity is suppressed.
      Under both uniform-luminance and drifting-grating stimulus conditions (but not in
      the dark), the discharges of pairs of LGN cells are highly correlated over long
      time scales; in contrast discharges of RGCs are nearly uncorrelated with each
      other. This indicates that action-potential activity at the LGN is subject to a
      common fractal modulation to which the RGCs are not subjected.

PMID- 11466003
TI  - Fractal probability measures of learning.
AB  - Herein we introduce a technique for determining the fractal dimension of time
      series obtained from complex systems, in particular brain-wave data in which the
      fractal dimension is arguably a measure of awareness and learning. The technique
      is based on determining the probability distribution for the degree of
      irregularity in random time series and has been shown to be superior in terms of
      efficiency and reliability to more commonly used methods that rely on the
      correlation function. We speculate that the scaling behavior of the probability
      measure is an indicator of an allometric relation between learning and brain-wave
      activity.

PMID- 11466004
TI  - The future of nurse education in Ireland.

PMID- 11466005
TI  - Nursing in a diverse community: a narrative review.
AB  - Almost 6% of Britain's population are of black or minority ethnic origin. There
      is increasing recognition that the health needs of such groups are not adequately
      met within the current health care system. One factor in reducing health
      inequalities is for health professionals to become culturally aware in order to
      serve these communities effectively. This literature review focuses on pre
      registration nursing programmes that address cultural sensitivity as part of
      basic training. The studies were selected by a computerized search of a number of
      databases and a hand search of selected nursing journals. The papers were
      reviewed under the following headings: setting, programme design, conceptual
      framework, curricula content, student assessment, and course evaluation. The
      programmes presented were undertaken predominantly in the USA. Either few
      programmes exist in the UK, or the programme details have not been published.
      Although, in the UK, cultural sensitivity training appears in its infancy, there
      are positive signs of change.

PMID- 11466006
TI  - Creating positive attitudes: the effects of knowledge and clinical experience of
      psychiatry in student nurse education.

PMID- 11466007
TI  - Peer review of classroom teaching: an interim report.
AB  - This paper provides interim findings from the implementation of peer review of
      classroom teaching in a large UK University School of Nursing, Midwifery and
      Health Visiting. A total of 258 classroom teaching sessions, involving 129
      teaching staff (n=129) were included over a period of 7 months. Teachers had two
      teaching sessions reviewed by a colleague. One reviewer was self-nominated and
      the Dean of School allocated the other. The paper is in two parts. Part one
      includes a short literature review followed by a descriptive account of how peer
      review was implemented. Part two focuses upon individual experiences from a small
      scale study with data obtained from 14 teachers (n=14) who took part in
      qualitative interviews based on their experiences of being both reviewer and
      reviewee. The larger study gathered data from several sources. This paper
      presents the initial findings from interview data with nurse teachers. Their
      perceptions form the basis of a discussion, which raises issues related to the
      experience of both implementing and being involved in, peer review of classroom
      teaching. Four themes emerged from the interview transcriptions; peer review was
      initially perceived as a threat; the experience of peer review was a positive
      one; teachers felt that being a reviewer was an interesting and worthwhile
      experience and perceived peer review positively when good relations existed
      between them and their reviewer.

PMID- 11466008
TI  - Barriers to the use of web-based learning in nurse education.
AB  - Amongst the themes that emerge and recur in the recent educational literature on
      the subject of web-based learning and teaching are how socio-economic factors and
      gender might influence the use of information technology (IT) by students.
      Writers often enthuse about how web-based learning will somehow reduce
      inequalities in student's access to education. However, in this paper it will be
      argued that most of the accounts in the literature of the potential of web-based
      learning take too little account of the potential problems and limitations of the
      medium. It could be argued that web-based learning underscores and may in fact
      increase inequalities rather than eliminate them. The aim of this paper is
      therefore twofold. First, it will examine the development of web-based learning
      and the potential ways it can be used. It will however be argued that the
      adoption of the medium has inherent difficulties, which are often overlooked or
      played down. Secondly, this paper will focus on those variables that could
      influence or inhibit student usage of web-based learning materials, in particular
      the influence of socio-economic factors and gender.

PMID- 11466009
TI  - Creating a climate for critical thinking in the preceptorship experience.
AB  - The impact of the learning climate on students' ability to think critically
      during preceptorship cannot be underestimated. The success of students in
      learning to think critically rests largely with the tone set by preceptors and
      staff (Myrick 1998). Students must be led gently into the active role of
      discussing, dialoguing, and problem solving (Meyers 1986). They watch very
      carefully how respectfully preceptors and staff field their comments, quickly
      notice nonverbal cues that indicate how open, approachable and supportive the
      preceptors and the staff are to their questions and contributions, and then
      discern how valued they are as colleagues. When preceptors genuinely value,
      support, and work with students in the practice setting and staff accept them as
      part of the team, a climate that is conducive to learning and critical thinking
      is established. This is due to the fact that students feel safe enough to
      question, to challenge and be challenged, and to be creative in their problem
      solving. The purpose of this paper is threefold: a) to identify key factors in
      the preceptorship experience that contribute to the creation of a climate that is
      conductive to critical thinking; b) to provide important insights into the role
      of the preceptor and the staff within that context; and c) to discuss how nursing
      faculty can more actively contribute to ensuring that such a learning climate is
      achieved in the preceptorship experience.

PMID- 11466010
TI  - Education for a new role: a review of neonatal nurse practitioner programmes.
AB  - A comparison was made of the different educational programmes developed to train
      Neonatal Nurse Practitioners (ENB A19) in the UK. The structure and character of
      the programmes were examined in relation to course aims and philosophies,
      learning outcomes, content, teaching strategies and methods of assessment.
      Documentation provided by course leaders included hand-books, timetables,
      teaching staff details and documents concerning supervision and assessment. When
      viewed closely there are differences between the programmes that are evident in
      design and curriculum content and which present a quality assurance issue to the
      institutions validating and running these programmes. The issue of parity and
      standards is also a critical one for those supporting the development regionally
      and nationally. Viewed within the broader perspective of post-registration nurse
      education, these relatively new programmes could be regarded as experiments in
      which professionals, as teachers and learners, are trying to address the changing
      boundaries of expertise and professional identities. It is suggested that the
      nurse practitioner programmes developed for neonatal care could provide a model
      for similar programmes in other specialties and argued that the experience gained
      in planning and running these courses could contribute positively to the
      development of other comparable educational programmes for established and
      experienced nurses.

PMID- 11466011
TI  - Clinical simulations: development and validation.
AB  - Simulations used as an educational strategy can mimic clinical reality bringing
      real life activity into the learning environment. This paper presents a
      conceptual approach to simulation development and validation that is applied to
      develop assessment simulations for both childbirth and triage situations. A
      process-based method of presenting information to the learner in the assessment
      phase is incorporated in simulations developed from actual clinical cases. The
      uncertain conditions of assessment are recognized as mirroring practice reality
      and validation of this construct and that of expertise are considered. Use of
      these simulations has the potential to provide learners with the opportunity to
      experience dimensions of simulated practice reality and educators with an
      experiential strategy that can be used to prepare students and also clinicians
      who are unfamiliar with new clinical practice areas.

PMID- 11466012
TI  - The classification of specialist student practice: results of an exploratory
      study.
AB  - An exploratory study investigating the feasibility and acceptability of an
      assessment tool designed to allow practice educators(1)to classify Specialist
      Practitioner student practice, identifies issues of interest to all educators
      involved with practice assessment. Within 3 months of commencing education
      leading to Specialist Practitioner Awards, the spread of marks awarded for
      practice achievements was already consistent with final degree classification and
      within 6 months slightly higher than normal. By the end of the course, continued
      improvements in practice achievements resulted in 73% of practice marks being 70%
      and over. The implications for total degree classification are less catastrophic
      than they appear; even if this trend continues there will only be a slight
      increase in first class Honours degrees. Although the strategy for practice
      assessment includes practice educators and students working together to discuss
      and agree marks for practice achievements, in the study practice educators and
      students provided marks intentionally without discussion or consultation with
      each other. Two comparisons of these marks showed that many students overestimate
      or underestimate their practice achievements as perceived by practice educators.
      Continuous monitoring of how marks are determined will be a priority for the
      Specialist Practice team. In most cases, practice educators considered the marked
      assessment of practice to be a reasonable working proposition, though there were
      concerns about the timing of assessments and the applied terminology. The main
      conclusions are that some practice educators may award marks for effort, despite
      contradictory written comments, and that the ability of specialist students to
      self-assess remains an unknown quantity but a potential moderating influence. The
      role of the HEI will be to ensure essential preparation and ongoing support for
      practice educators to enable a tri-partite assessment process and to provide a
      robust strategy for internal and external moderation. The marked assessment of
      practice was implemented in September 2000; to date progress has been remarkably
      unproblematic with practice educators and students accepting the process with
      relative ease and much enthusiasm.

PMID- 11466013
TI  - Accreditation of Prior (Experiential) Learning: making the difference.
AB  - This paper considers the use of Accreditation of Prior (Experiential) Learning
      (AP[E]L) in pre registration nurse education. AP(E)L has opened up many new
      prospects in post registration nurse education but opportunities for pre
      registration have, to date, been few. The time for change, however, is upon us
      all, most particularly for those institutions which have been selected to develop
      a new approach to nurse education referred to in Making a Difference, published
      by the Department of Health in 1999 and Fitness for Practice, published by the
      UKCC in 1999. As one of the selected sites the Institute of Health Studies at the
      University of Plymouth, in conjunction with the Cornwall and South Devon and
      Somerset and North Devon Education Purchasing Consortia, is in the process of
      implementing those required changes. One of the changes integral to the new
      curriculum is that of AP(E)L for entry to, and exit from, pre registration nurse
      education.

PMID- 11466018
TI  - Course of chronic focal epilepsy resistant to anticonvulsant treatment.
AB  - Sixty-three patients (32 women, 31 men), chronically treated with carbamazepine,
      phenytoin, valproate and/or phenobarbital, were investigated. Mean age at
      manifestation of epilepsy was 16.4 years; mean age at onset of documentation of
      seizure frequency was 33.7 years; mean duration of follow-up was 104.8 months;
      mean number of documented seizures per patient was 313.2. A statistical analysis
      of seizure diaries was performed. For each day the entries were the number of
      seizures per day. Linear trends, the amount of variance of the seizure frequency
      compared to randomly distributed events, were computed with the resulting
      coefficients fitting a general linear regression model. Non-random aggregations
      (clusters) were searched for as well as gaps of seizure manifestation. A similar
      number of patients exhibited a decrease (30%) or increase (29%) of seizure
      frequency during the course of epilepsy. The variance of the daily seizure
      frequency was in most patients (78%) significantly higher or lower (5%) than
      corresponding random distributions. The coupling coefficient to the day before
      was significantly larger than zero (indicating seizure clustering) in 57% of
      patients. Significant rhythmic components in seizure profiles (quasi-weekly or
      quasi-monthly) were found in 31 patients (both male and female). Periods of
      increased seizure frequency (clusters) manifested in 62% of patients; seizure
      gaps of at least 1 year occurred in 29 patients followed by seizure relapses in
      20 patients. In conclusion, there is no evidence for a unique type of course in
      chronic focal epilepsy in patients on antiepileptic drugs.

PMID- 11466019
TI  - A prospective comparison between two seizure classifications.
AB  - The International Classification of Epileptic Seizures is the most widely used,
      but an alternative system based purely on ictal symptoms and signs has been
      proposed: the semiological classification. Our objective was to compare the two
      in a sample of patients evaluated at epilepsy centers. We collected 78
      consecutive patients evaluated in outpatient epilepsy clinics who subsequently
      underwent noninvasive video-EEG monitoring at three centers. Patients with
      pseudoseizures were excluded. Seizures were first classified based on information
      obtained during clinic visits, and again after video-EEG monitoring. Each time,
      seizures were classified using both the International Classification and the
      semiological classification. Eventual epilepsy syndrome diagnosis was based on
      all the clinical data, video-EEG monitoring, and other independent tests
      including imaging studies. Sixty-six (87%) patients were classified as having
      'complex partial seizures' in the International Classification. Using the
      semiological classification, these same 66 patients were classified as follows:
      automotor (34), dialeptic (17), hypermotor (13), hypomotor (2). Seizure
      classification changed between initial 'clinic-based' data and the 'monitoring
      based' classification in 27 cases using the ILAE, vs. six using the semiological
      classification. Seizure classification tended to change significantly between pre
      and post-monitoring using the ILAE but not the semiological classification. The
      term complex partial seizure included multiple categories of the semiological
      classification, and was very nonspecific. The semiological classification may be
      better suited for everyday clinic use, since it is based solely on clinical
      characteristics.

PMID- 11466020
TI  - The effects of refractory epilepsy on intellectual functioning in children and
      adults. A longitudinal study.
AB  - The aim of this study was to compare the long-term consequences of refractory
      epileptic seizures for intellectual functioning in pediatric and adult patients,
      taking the severity of the epilepsy into consideration. Thirty-four patients, 17
      children (mean age 10.2 years) and 17 adults (mean age 24.4 years) were tested
      twice with the age-appropriate version of Wechsler's Intelligence Scales. The
      mean test-retest interval in the two groups was 3.5 and 6.0 years, respectively.
      There were no statistically significant differences between the groups with
      respect to severity of the epilepsy at Test 1, as indicated by retrospective
      assessments of seizure severity, interictal EEG pathology, and number of
      antiepileptic drugs received per patient. Assessments of changes in these
      variables during the test-retest interval did not indicate different courses of
      the disease in the two groups. Despite these similarities, a statistically
      significant difference was found between the children and the adults regarding
      changes in intellectual functioning. In the children, there was a decline in mean
      intelligence quotient (IQ) scores during the test-retest interval, while the IQ
      scores increased in the adult group. It is concluded that recurrent seizures may
      represent a considerable risk for intellectual decline in children, while
      intellectual functioning seem to be less vulnerable in adults with early onset of
      epilepsy.

PMID- 11466021
TI  - SPECT in periodic lateralized epileptiform discharges (PLEDs): a form of partial
      status epilepticus?
AB  - Periodic lateralized epileptiform discharges (PLEDs) are a well defined
      electroencephalographic entity but whether PLEDs represent an ictal condition or
      not remains debated. Much work has been done using electroencephalography (EEG)
      but new approaches using cerebral perfusion imaging may give more information
      about this question. We aimed to evaluate if PLEDs were associated with high
      regional cerebral blood flow (rCBF). We studied 18 patients with PLEDs and
      different pathologies, and performed brain single-photon-emission computed
      tomography (SPECT) during and, for three cases, after the disappearance of PLEDs.
      Qualitative variations and locations of rCBF were compared with PLEDs.
      Association with seizures and type of seizures were also assessed. SPECT showed
      high rCBF in 18/18 patients (100%). The location of PLEDs and high rCBF matched
      in 17/18 cases (94%). In the three cases where SPECT was performed after PLEDs
      disappeared, the high rCBF had cleared (100%). Eighteen cases (100%) presented
      seizures before recording of PLEDs, mainly motor (partial motor or generalized
      tonic-clonic). Where there was a decreased rCBF (related to a lesion) there was
      little relationship to PLEDs and all patients with decreased rCBF had an adjacent
      increased rCBF. These results confirm preliminary case reports. Hyperperfusion
      adds further to the argument that PLEDs may be related to a form of partial
      status epilepticus.

PMID- 11466022
TI  - Problems with phenytoin administration in neurology/neurosurgery ITU patients
      receiving enteral feeding.
AB  - Our objective was to investigate the relationship between phenytoin
      bioavailability, enteral feeding and serum albumin levels in patients admitted to
      neurology/neurosurgery ITU, via case studies of three patients. The research was
      performed at the Walton centre for Neurology and Neurosurgery NHS Trust,
      Liverpool, England, and our subjects consisted of three cases admitted to ITU (1
      status epilepticus, 1 post-trauma and 1 post-subarachnoid haemorrhage (SAH)).
      Phenytoin levels were assessed in relation to the type of feeding and serum
      albumin levels. We found evidence of a complex relationship between phenytoin
      levels, enteral feeding and serum albumin in patients in the neuro ITU setting.
      We conclude that, in this setting the patient's phenytoin needs to be closely
      monitored and treated aggressively to maintain therapeutic levels. They should
      also be followed up during rehabilitation to avoid toxicity.

PMID- 11466023
TI  - Autonomic nervous system activity and life threatening arrhythmias in
      experimental epilepsy.
AB  - In the present study the possible derangement of the autonomic system and its
      influence in life threatening arrhythmias were analysed during paroxysmal
      activity. In hemispherectomized rats a paroxysmal activation of the hypothalamic
      and mesencephalic cardioarrhythmogenic triggers was performed by topical
      application of penicillin-G. Blood gas parameters and electrical activity of the
      thalamus, hypothalamus, vagal nerve fibre, ECG and arterial blood pressure were
      simultaneously monitored in basal conditions and repeated after the appearance of
      paroxysmal activity. Temporal correlation analysis was carried out. Results
      showed that during activation of these triggers, the spontaneous vagal nerve
      fibre activity significantly increased and triggered the appearance of cardiac
      arrhythmias which could become life threatening and induce animal death when
      blood gas and electrolytic parameters were simultaneously impaired. These
      experiments suggest that fatal evolution of the heart impairment is related not
      only to an autonomic cardiac trigger, but also to a concomitant metabolic
      derangement, which most likely shares the same autonomic origin.

PMID- 11466024
TI  - Levetiracetam does not modulate neuronal voltage-gated Na+ and T-type Ca2+
      currents.
AB  - This study investigated whether the mechanism of action of levetiracetam (LEV) is
      related to effects on neuronal voltage-gated Na+ or T-type Ca2+currents. Rat
      neocortical neurones in culture were subjected to the whole-cell mode of voltage
      clamping under experimental conditions designed to study voltage-gated Na+
      current. Additionally, visually identified pyramidal neurones in the CA1 area of
      rat hippocampal slices were subjected to the whole-cell mode of voltage clamping
      under experimental conditions designed to study low-voltage-gated (T-type) Ca2+
      current. LEV (10 microM-1 mM) did not modify the Na+ current amplitude and did
      not change (200 microM) the steady-state activation and inactivation, the time to
      peak, the fast kinetics of the inactivation and the recovery from the steady
      state inactivation of the Na+ current. Likewise, LEV (32-100 microM) did not
      modify the amplitude and did not change the steady-state activation and
      inactivation, the time to peak, the fast kinetics of the inactivation and the
      recovery from the steady-state inactivation of the T-type Ca2+current. In
      conclusion, neuronal voltage-gated Na+ channels do not appear directly involved
      in the antiepileptic mechanism of action of LEV, and LEV was devoid of effect on
      the low-voltage-gated (T-type) Ca2+ current in hippocampal neurones.

PMID- 11466025
TI  - Neuroprotective properties of the novel antiepileptic drug levetiracetam in the
      rat middle cerebral artery occlusion model of focal cerebral ischemia.
AB  - Levetiracetam (LEV) is a new antiepileptic drug with a promising preclinical
      profile involving both anticonvulsant and antiepileptogenic effects in kindling
      models. The latter stimulated the present study to compare its neuroprotective
      properties with the potent and selective, non-competitive NMDA antagonist, MK
      801, in the rat middle cerebral artery occlusion model. Twenty-four hours after a
      transient occlusion of 90 minutes the animals were sacrificed and infarct volume
      and lesion distribution were determined from stained coronal sections. LEV was
      administered by intraperitoneal (i.p.) bolus injections of 5.5, 11, 22 and 44 mg
      x kg(-1), 30 minutes before occlusion followed by a continuous 24 hour i.p.
      infusion of 1.25, 2.6, 5.1 and 10.2 mg x kg(-1) per hour, respectively. LEV
      administration did not alter body temperature but reduced the infarct volume by
      33% (P< 0.05) at the highest dose tested. An i.p. bolus injection of 0.04, 0.12
      and 0.4 mg x kg(-1) of MK-801 followed by continuous i.p. infusion of 0.036,
      0.108 and 0.36 mg x kg(-1) per hour, reduced the infarct volume by 49, 51 and 74%
      (P< 0.05), respectively. However, only the highest dose of MK-801 induced a
      significant reduction in the infarct volume (P< 0.05) and this was associated
      with hypothermia. These results suggest that LEV possesses neuroprotective
      properties which may be relevant for its antiepileptogenic action.

PMID- 11466026
TI  - Area-selective stimulus-provoked seizures in post-anoxic coma.
AB  - We describe the case of a 70-year-old patient in whom hemiconvulsive seizures
      occurred during metabolic derangement, multiple stroke and post-anoxic coma
      following cardiac arrest. We employed the methods of clinical and EEG evaluation
      and CT brain scan. We found that hemiconvulsive seizures were provoked following
      a light tactile stimulus in the left-trigeminal area and occasionally a strong
      tapping in the right-trigeminal area. We conclude that this type of stimulus
      provoked seizure is extremely rare and could be explained by diffuse and severe
      brain damage.

PMID- 11466027
TI  - Bilateral fronto-occipital polymicrogyria and epilepsy.
AB  - We present a clinico-pathological case report in which both cortical dysplasia
      and epilepsy coexisted: a 30 year old male who was dead on arrival at hospital.
      One and a half hours earlier he had developed complex partial status with peri
      oral cyanosis. At post mortem examination his brain showed bilateral occipital
      frontal polymicrogyria with unlayered neuronal migration disorder; in other parts
      there were fourth layer migration disorders. The white matter exhibited
      multicystic encephalopathy. In the heart there was chronic interstitial and
      perivascular fibrosis, although he died of a cardiac arrest. Bilateral frontal
      occipital polymicrogyria is highly epileptogenic. This was a sporadic case and we
      cannot define a clear aetiology. There was a pathological cardiac condition
      without previous vascular risk factors which might be related to repetition of
      seizures and possibly to his sudden death during status epilepticus.

PMID- 11466028
TI  - Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS).
AB  - The aim of this paper is to report a patient with late-onset myoclonic epilepsy
      in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset
      progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is
      described who developed progressively frequent myoclonus and generalized
      myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated
      background slowing and generalized polyspike-wave discharges occasionally
      associated with myoclonic jerks, leading to the classification of primary
      generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS
      patients are rare. However, a review of the pertinent literature revealed at
      least two other cases of elderly DS patients developing progressive myoclonic
      epilepsy after the onset of dementia. We suggest that late-onset myoclonic
      epilepsy in Down's syndrome as characterized here should be considered in the
      differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently
      shares features with myoclonic epilepsy in Alzheimer's disease (AD) and
      Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since
      life expectation of DS patients has markedly increased, LOMEDS may be more
      frequent than currently acknowledged.

PMID- 11466029
TI  - The epidemiology of epilepsy: the size of the problem.
AB  - The prevalence of epilepsy is generally taken as between 5 and 10 cases per 1000
      persons, and the overall incidence as about 50 cases per 100 000 persons. The
      rates are dependent on case ascertainment and on definitions used. The prognosis
      depends on many factors, including the number of seizures at presentation, the
      seizure type and the use of anti-epileptic drugs. Epilepsy carries an excess
      mortality; the cause of death can be unrelated to epilepsy, related to the
      underlying disease causing epilepsy, or related to epilepsy itself.

PMID- 11466031
TI  - Mycobacterium bovis infection in wildlife in New Zealand.
AB  - Bovine tuberculosis (Tb) is the most important disease of livestock in New
      Zealand, and it puts at risk the nation's trade in dairy, beef and venison
      products. Elimination of the disease from livestock is based on a herd test and
      slaughter programme and carcass inspection at abbatoirs. However, this programme
      has not been as successful as expected, because the disease also occurs in wild
      or feral animals acting as vectors of the disease to livestock. Brushtail possums
      are the major wildlife vector and self-sustaining maintenance host of Tb, and
      play a role analogous to that of the badger in Great Britain. In contrast, some
      deer species and ferrets may act as vectors of the disease, but their role in
      transmitting Tb to livestock is unclear. Hedgehogs, pigs, cats, sheep and goats
      are now considered to be amplifier hosts, and spread the disease to other species
      only when inspected or their carcasses scavenged. In the absence of infected
      possum populations, these species do not appear to be capable of maintaining the
      infection in their own populations and are not thought to be involved in the
      maintenance of Tb in livestock. Tuberculosis has also been recorded from stoats,
      hares, and a rabbit, but the level of infection recorded in their populations
      indicates these species are unlikely to spread the disease to other animals and
      hence are not involved in the transmission of Tb to livestock.

PMID- 11466032
TI  - Occurrence of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in tuberculous pleuritis.
AB  - OBJECTIVE: Matrix metalloproteinases (MMP) and tissue inhibitors of
      metalloproteinases (TIMP) have been found in high concentrations in pleural
      effusions. Because MMP and TIMP may play a part in the causation of the fibrosis
      seen in tuberculous (TB) pleuritis their occurrence was examined. DESIGN: Pleural
      effusion fluid and plasma concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9,
      TIMP-1 and TIMP-2 were determined by ELISA in 21 patients with TB pleuritis. To
      adjust for the total protein content, respective ratios were calculated.
      Activities of MMP-2 and MMP-9 were measured by gelatine zymography and the MMP
      9/MMP-2 ratios calculated. Pleural effusions and plasma of 15 patients with
      congestive heat failure (CHF) and plasma of 15 healthy persons (CON) served as
      controls. RESULTS: Immunoreactive pleural fluid concentrations of MMP-1, MMP-2,
      MMP-8, and MMP-9 were higher in TB compared to CHF, but plasma concentrations
      were not different between the groups. TB pleural fluid concentrations of MMP-1,
      MMP-2, TIMP-1, and TIMP-2 were higher compared to TB plasma. MMP-3 was found in
      trace amounts only. The MMP-9/total protein ratios in pleural fluid were higher
      in TB compared to CHF (0.4492+/-0.1633 vs 0.0364+/-0.0145, P<0.005) but the TIMP
      1 ratios were lower (139.0+/-28.7 vs 517.8+/-183.7, P<0.0005). In TB pleural
      fluid vs TB plasma, the respective MMP-1, MMP-2, TIMP-1, and TIMP-2 ratios were
      increased (0.46+/-0.10 vs 0.17+/-0.02; 25.2+/-2.8 vs 4.2+/-0.9; 139.0+/-28.7 vs
      27.8+/-8.2; 0.67+/-0.13 vs 0.18+/-0.04, P<0.0005 each). Gelatine zymography
      demonstrated MMP-2 and MMP-9 bands of different brightness in TB effusions but in
      CHF effusions the MMP-9 band was barely visible. The MMP-9/MMP-2 effusion ratios
      were therefore higher in TB compared to CHF (0.46+/-0.15 vs 0.05+/-0.04,
      P<0.0005). CONCLUSION: Compartmentalized MMP-1, MMP-2, TIMP-1, and TIMP-2 and,
      compared to CHF, a surplus of MMP-1, MMP-2, MMP-8, and MMP-9 in the pleural space
      obviously contribute to the fibrotic reactions in TB pleuritis.

PMID- 11466033
TI  - Demonstration of reinfection and reactivation in HIV-negative autopsied cases of
      secondary tuberculosis: multilesional genotyping of Mycobacterium tuberculosis
      utilizing IS 6110 and other repetitive element-based DNA fingerprinting.
AB  - SETTING: Secondary tuberculosis may follow reinfection or endogenous
      reactivation. The design of effective preventive and treatment protocols requires
      knowledge about the relative importance of these mechanisms in specific
      communities. Molecular typing of Mycobacterium tuberculosis has permitted linkage
      of cases and demonstration of patterns of inter- or intrapatient strain diversity
      correlating with reinfection and reactivation. OBJECTIVE: The use of DNA
      fingerprinting to examine intrapatient strain diversity in autopsied, HIV
      negative individuals resident in a high incidence community. DESIGN: Autopsy (12
      cases) and pneumonectomy (one case) permitted multilesional sampling for
      bacterial culture and comparative genotyping. Mycobacterium tuberculosis strains
      were typed using probes directed against IS 6110, the direct repeat sequence (DR)
      and MTB484(1). RESULTS: In two patients, the demonstration of pulmonary infection
      by two distinct strains suggested dual infection of these individuals. In one
      other case, the strain isolated from a Ghon-focus was identical to that obtained
      from all secondary cavitating lesions, which suggested reactivation of the
      primary infection. In the remaining cases, all isolates were identical, but
      primary lesions could not be identified with certainty or were culture negative.
      One of these cases showed evidence of strain evolution. CONCLUSIONS:
      Multilesional strain genotyping suggested both reinfection and reactivation in a
      series of HIV-negative autopsied patients with secondary tuberculosis. In most
      (11/13) cases, the same strain (or clonal variant) was present in all lesions,
      pulmonary and extrapulmonary.

PMID- 11466034
TI  - Dialogue between Mycobacterium tuberculosis and Homo sapiens.

PMID- 11466035
TI  - Progressive pulmonary tuberculosis is not due to increasing numbers of viable
      bacilli in rabbits, mice and guinea pigs, but is due to a continuous host
      response to mycobacterial products.
AB  - Tuberculosis (TB) kills more people in the world today than any other infectious
      disease. A better vaccine to prevent clinical tuberculosis is greatly needed.
      Candidate vaccines are often evaluated by infecting rabbits, mice and guinea pigs
      by an aerosol of virulent tubercle bacilli and culturing their lungs for viable
      bacilli at various times thereafter. In all three species, however, the number of
      viable bacilli usually does not continuously increase until the host succumbs.
      The number of viable bacilli increases logarithmically for only about 3 weeks.
      Then, the host develops delayed-type hypersensitivity (DTH) and cell-mediated
      immunity (CMI), which keep the number of viable bacilli rather constant during
      the subsequent weeks. In the immunized host, DTH and CMI stop the logarithmic
      increase sooner than in the unimmunized controls, so that the stationary
      bacillary levels that follow are lower. This review analyzes host-parasite
      interactions in the lungs of rabbits, mice and guinea pigs. All three species
      cannot prevent inhaled fully virulent tubercle bacilli from establishing an
      infection, but they differ markedly in the type of the disease produced once it
      is established.

PMID- 11466036
TI  - The use of adenosine deaminase as a diagnostic tool for peritoneal tuberculosis.
AB  - SETTING: Tygerberg Hospital, an academic hospital in the Western Cape, South
      Africa. OBJECTIVE: To determine the diagnostic utility of ascitic fluid adenosine
      deaminase (ADA) in the diagnosis of tuberculous peritonitis. DESIGN: A
      prospective study, carried out from February 1995 to February 1998, resulted in
      178 paired ascites and serum specimens being collected from adult patients.
      Specimens were evaluated for biochemistry, ADA, microbiology and cytology;
      further investigations were done at the treating clinician's discretion.
      Diagnoses were made according the pre-determined criteria. RESULTS: The median
      (range) ADA activity in the tuberculous group was 61.6 (17.5--115.0) U/L and was
      significantly higher than in any other diagnostic group (p<0.05). Using ROC
      curves, a cut-off level of 30 U/L for the diagnosis of tuberculous peritonitis
      was found to yield the best results; corresponding sensitivity and specificity
      was 94% and 92%, respectively. No statistically significant difference in ADA
      activity was observed when tuberculous ascites occurred in the absence or
      presence of cirrhosis. CONCLUSIONS: Ascitic fluid ADA activity is useful in
      identifying those patients in whom the diagnosis of tuberculous peritonitis
      should be actively pursued to justify its routine use, at least in areas such as
      South Africa where TB is endemic. The presence or absence of underlying cirrhosis
      does not appear to distract from its diagnostic utility.

PMID- 11466037
TI  - Specific and early detection of IgG, IgA and IgM antibodies to Mycobacterium
      tuberculosis 38kDa antigen in pulmonary tuberculosis.
AB  - The objective was to apply the purified 38kDa protein antigen of Mycobacterium
      tuberculosis in ELISA to estimate the IgG, IgA and IgM antibody levels in sera
      and circulating immune complexes of tuberculosis patients. Sera from smear and
      culture positive tuberculosis patients were positive for anti 38kDa IgG, IgA and
      IgM antibodies, with a sensitivity of 61%, 30% and 10%, respectively, and with a
      specificity of 100% for IgG. The sensitivity of the test improved to a level of
      68% for IgG+IgA and of 71.4% for IgG+IgA+IgM without significantly compromising
      the specificity (IgG of 100%, IgG+IgA of 96%, IgG+IgA+IgM of 90%). Among the
      smear, culture-negative but X-ray-positive cases, 60% were serum positive for IgG
      antibody, while in smear-negative but culture-positive cases, 54% were positive
      for IgG antibody. Measurement of 38kDa antibodies showed a greater than 95%
      sensitivity in smear and culture-positive, and smear-negative and culture
      positive patients, through a combination of assays for serum IgG and circulating
      immune complex antibodies, while the specificity was 100%.

PMID- 11466038
TI  - A Prussian blue nanomolecule: crystal structure and low-temperature magnetism.

PMID- 11466039
TI  - Cooperative spin crossover behavior in cyanide-bridged Fe(II)-M(II) bimetallic 3D
      Hofmann-like networks (M = Ni, Pd, and Pt).

PMID- 11466040
TI  - Low-temperature elemental-direct-reaction route to II-VI semiconductor
      nanocrystalline ZnSe and CdSe.

PMID- 11466041
TI  - Redox-induced terpyridyl substitution in the Os(VI)-hydrazido complex, trans
      [Os(VI)(tpy)(Cl)(2)(NN(CH(2))(4)O)](2+).
AB  - Reaction between the Os(VI)-hydrazido complex, trans
      [Os(VI)(tpy)(Cl)(2)(NN(CH(2))(4)O)](2+) (tpy = 2,2':6',2"-terpyridine and
      O(CH(2))(4)N(-) = morpholide), and a series of N- or O-bases gives as products
      the substituted Os(VI)-hydrazido complexes, trans-[Os(VI)(4'
      RNtpy)(Cl)(2)(NN(CH(2))(4)O)](2+) or trans-[Os(VI)(4'
      ROtpy)(Cl)(2)(NN(CH(2))(4)O)](2+) (RN(-) = anilide (PhNH(-)); S,S-diphenyl
      sulfilimide (Ph(2)S=N(-)); benzophenone imide (Ph(2)C=N(-)); piperidide
      ((CH(2))(5)N(-)); morpholide (O(CH(2))(4)N(-)); ethylamide (EtNH(-));
      diethylamide (Et(2)N(-)); and tert-butylamide (t-BuNH(-)) and RO(-) = tert
      butoxide (t-BuO(-)) and acetate (MeCO(2)(-)). The rate law for the formation of
      the morpholide-substituted complex is first order in trans
      [Os(VI)(tpy)(Cl)(2)(NN(CH(2))(4)O)](2+) and second order in morpholine with
      k(morp)(25 degrees C, CH(3)CN) = (2.15 +/- 0.04) x 10(6) M(-)(2) s(-)(1).
      Possible mechanisms are proposed for substitution at the 4'-position of the tpy
      ligand by the added nucleophiles. The key features of the suggested mechanisms
      are the extraordinary electron withdrawing effect of Os(VI) on tpy and the
      ability of the metal to undergo intramolecular Os(VI) to Os(IV) electron
      transfer. These substituted Os(VI)-hydrazido complexes can be electrochemically
      reduced to the corresponding Os(V), Os(IV), and Os(III) forms. The Os-N bond
      length of 1.778(4) A and Os-N-N angle of 172.5(4) degrees in trans-[Os(VI)(4'
      O(CH(2))(4)Ntpy)(Cl)(2)(NN(CH(2))(4)O)](2+) are consistent with sp-hybridization
      of the alpha-nitrogen of the hydrazido ligand and an Os-N triple bond. The
      extensive ring substitution chemistry implied for the Os(VI)-hydrazido complexes
      is discussed.

PMID- 11466042
TI  - Synthesis of triamidoamine ligands of the type (ArylNHCH(2)CH(2))(3)N and
      molybdenum and tungsten complexes that contain an [ArylNCH(2)CH(2))(3)N]3-
      ligand.
AB  - Aryl bromides react with (H(2)NCH(2)CH(2))(3)N in a reaction catalyzed by
      Pd(2)(dba)(3) in the presence of BINAP and NaO-t-Bu to give the arylated
      derivatives (ArylNHCH(2)CH(2))(3)N [Aryl = C(6)H(5) (1a), 4-FC(6)H(4) (1b), 4-t
      BuC(6)H(4) (1c), 3,5-Me(2)C(6)H(3) (1d), 3,5-Ph(2)C(6)H(3) (1e), 3,5-(4-t
      BuC(6)H(4))(2)C(6)H(3) (1f), 2-MeC(6)H(4) (1g), 2,4,6-Me(3)C(6)H(2) (1h)].
      Reactions between (ArNHCH(2)CH(2))(3)N (Ar = C(6)H(5), 4-FC(6)H(4), 3,5
      Me(2)C(6)H(3), and 3,5-Ph(2)C(6)H(3)) and Mo(NMe(2))(4) in toluene at 70 degrees
      C lead to [(ArNHCH(2)CH(2))(3)N]Mo(NMe(2)) complexes in yields ranging from 64 to
      96%. Dimethylamido species (Ar = 4-FC(6)H(4), 3,5-Me(2)C(6)H(3)) could be
      converted into paramagnetic [(ArNHCH(2)CH(2))(3)N]MoCl species by treating them
      with 2,6-lutidinium chloride in tetrahydrofuran (THF). The "direct reaction"
      between 1a-f and MoCl(4)(THF)(2) in THF followed by 3 equiv of MeMgCl yielded
      [(ArNHCH(2)CH(2))(3)N]MoCl species (3a-f) in high yield. If 4 equiv of LiMe
      instead of MeMgCl are employed in the direct reaction, then
      [(ArNHCH(2)CH(2))(3)N]MoMe species are formed. Tungsten species,
      [(ArNHCH(2)CH(2))(3)N]WCl, could be prepared by analogous "direct" methods.
      Cyclic voltammetric studies reveal that MoCl complexes become more difficult to
      reduce as the electron donating ability of the [ArylNCH(2)CH(2))(3)N]3- ligand
      increases, and the reductions become less reversible, consistent with ready loss
      of chloride from ([(ArNHCH(2)CH(2))(3)N]MoCl)(-). Tungsten complexes are more
      difficult to reduce, and reductions are irreversible on the CV time scale.

PMID- 11466043
TI  - Synthesis, structure, and electrochemical studies of molybdenum and tungsten
      dinitrogen, diazenido, and hydrazido complexes that contain aryl-substituted
      triamidoamine ligands.
AB  - One-electron reduction of [ArN(3)N]MoCl complexes (Ar = C(6)H(5), 4-FC(6)H(4), 4
      t-BuC(6)H(4), 3,5-Me(2)C(6)H(3)) yields complexes of the type [ArN(3)N]Mo-N=N
      Mo[ArN(3)N], while two-electron reduction yields ([ArN(3)N]Mo-N=N)(-) derivatives
      (Ar = C(6)H(5), 4-FC(6)H(4), 4-t-BuC(6)H(4), 3,5-Me(2)C(6)H(3), 3,5
      Ph(2)C(6)H(3), and 3,5-(4-t-BuC(6)H(4))(2)C(6)H(3)). Compounds that were
      crystallographically characterized include ([t-BuC(6)H(4)N(3)N]Mo)(2)(N(2)),
      Na(THF)(6)([PhN(3)N]Mo-N=N)(2)Na(THF)(3), [t-BuC(6)H(4)N(3)N]Mo-N=N-Na(15-crown
      5), and ([Ph(2)C(6)H(3)N(3)N]MoNN)(2)Mg(DME)(2). Compounds of the type
      [ArN(3)N]Mo-N=N-Mo[ArN(3)N] do not appear to form when Ar = 3,5-Ph(2)C(6)H(3) or
      3,5-(4-t-BuC(6)H(4))(2)C(6)H(3), presumably for steric reasons. Treatment of
      diazenido complexes (e.g., [ArN(3)N]Mo-N=N-Na(THF)(x)) with electrophiles such as
      Me(3)SiCl or MeOTf yielded [ArN(3)N]Mo-N=NR complexes (R = SiMe(3) or Me). These
      species react further to yield ([ArN(3)N]Mo-N=NMe(2))(+) species in the presence
      of methylating agents. Addition of anionic methyl reagents to ([ArN(3)N]Mo
      N=NMe(2))(+) species yielded [ArN(3)N]Mo(N=NMe(2))(Me) complexes. Reduction of [4
      t-BuC(6)H(4)N(3)N]WCl under dinitrogen leads to a rare ([t
      BuC(6)H(4)N(3)N]W)(2)(N(2)) species that can be oxidized by two electrons to give
      a stable dication (as its BPh(4)(-) salt). Reduction of hydrazido species leads
      to formation of Mo=N in low yields, and only dimethylamine could be identified
      among the many products. Electrochemical studies revealed expected trends in
      oxidation and reduction potentials, but also provided evidence for stable neutral
      dinitrogen complexes of the type [ArN(3)N]Mo(N(2)) when Ar is a relatively bulky
      terphenyl substituent.

PMID- 11466044
TI  - Complex formation constants for the aqueous copper(I)-acetonitrile system by a
      simple general method.
AB  - A simple spectrophotometric method for the evaluation of formation constants for
      aqueous copper(I) has been developed, based on the kinetics of reduction of
      Co(III)(NH(3))(5)X complexes. The method has been applied to the aqueous
      copper(I)-acetonitrile system to determine the successive formation constants
      beta(1), beta(2), and beta(3) as 4.3 x 10(2) M(-)(1), 1.0 x 10(4) M(-)(2), and
      2.0 x 10(4) M(-)(3), respectively, in 0.14 M NaClO(4)/HClO(4) at 21 +/- 1 degrees
      C.

PMID- 11466045
TI  - Chelate effect in the gas phase. The complexes of Ni(2,2,6,6-tetramethyl-3,5
      heptanedionate)(2) with bidentate ligands.
AB  - When a bidentate ligand L-L is added to the square planar Ni(tmhd)(2) (tmhd =
      tetramethylhepanedionate), the octahedral complex Ni(tmhd)(2)L-L is formed. This
      reaction has been studied by vis spectroscopy in toluene at 25 degrees C and in
      the gas phase between 150 and 350 degrees C. It allows the comparison on one hand
      of the chelate effect of three ligands forming five-membered chelate rings: (i)
      the flexible N-N ligand tetramethylethylenediamine (TEME); (ii) the rigid N-N
      ligand 2,2-bipyridine (BPY); (iii) the flexible N-O ligand
      dimethylaminomethoxyethane (MAO). On the other hand, it allows the comparison of
      these ligands with the six-membered chelate ring-forming N-N ligand 1,3
      tetramethylpropylenediamine (TEMP). From the temperature dependence of the gas
      phase stability constants, enthalpies and entropies of the complex-forming
      reactions have been derived. As there are no solvation effects in the gas phase,
      the reaction enthalpies are the metal-ligand bond enthalpies. This is of
      particular interest for the hemilabile ligand MAO. For the N-N ligands, the
      stability of the metal-ligand bonds decreases in the order TEME > BPY > TEMP. The
      entropy of the complex formation with the two flexible ligands TEME and MAO is
      the same, while it is slightly more positive for the rigid BPY and a lot more
      positive for TEMP. Delta(form)G degrees (298) of the complexes is more negative
      in the gas phase than in solution because the solvation energy of the reactants
      is more negative than the solvation energy of the products. This is shown in
      detail for the formation of Ni(tmhd)(2)BPY where data of a complete thermodynamic
      cycle are presented.

PMID- 11466046
TI  - New class of oligonuclear platinum-thallium compounds with a direct metal-metal
      bond. 5. Structure determination of heterodimetallic cyano complexes in aqueous
      solution by EXAFS and vibrational spectroscopy.
AB  - The structures of three closely related heterodimetallic cyano complexes,
      [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) (n = 1-3), formed in reactions between
      [Pt(II)(CN)(4)](2)(-) and Tl(III) cyano complexes, have been studied in aqueous
      solution. Multinuclear NMR data ((205)Tl, (195)Pt, and (13)C) were used for
      identification and quantitative analysis. X-ray absorption spectra were recorded
      at the Pt and Tl L(III) edges. The EXAFS data show, after developing a model
      describing the extensive multiple scattering within the linearly coordinated
      cyano ligands, short Pt-Tl bond distances in the [(NC)(5)Pt-Tl(CN)(n)()](n)()(-)
      complexes: 2.60(1), 2.62(1), and 2.64(1) A for n = 1-3, respectively. Thus, the
      Pt-Tl bond distance increases with increasing number of cyano ligands on the
      thallium atom. In all three complexes the thallium atom and five cyano ligands,
      with a mean Pt-C distance of 2.00-2.01 A, octahedrally coordinate the platinum
      atom. In the hydrated [(NC)(5)Pt-Tl(CN)(H(2)O)(4)](-) species the thallium atom
      coordinates one cyano ligand, probably as a linear Pt-Tl-CN entity with a Tl-C
      bond distance of 2.13(1) A, and possibly four loosely bound water molecules with
      a mean Tl-O bond distance of about 2.51 A. In the [(NC)(5)Pt-Tl(CN)(2)](2)(-)
      species, the thallium atom probably coordinates the cyano ligands trigonally with
      two Tl-C bond distances at 2.20(2) A, and in [(NC)(5)Pt-Tl(CN)(3)](3)(-) Tl
      coordinates tetrahedrally with three Tl-C distances at 2.22(2) A. EXAFS data were
      reevaluated for previously studied mononuclear thallium(III)-cyano complexes in
      aqueous solution, [Tl(CN)(2)(H(2)O)(4)](+), [Tl(CN)(3)(H(2)O)], and [Tl(CN)(4)](
      ), and also for the solid K[Tl(CN)(4)] compound. A comparison shows that the Tl-C
      bond distances are longer in the dinuclear complexes [(NC)(5)Pt
      Tl(CN)(n)()](n)()(-) (n = 1-3) for the same coordination number. Relative
      oxidation states of the metal atoms were estimated from their (195)Pt and (205)Tl
      chemical shifts, confirming that the [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) complexes
      can be considered as metastable intermediates in a two-electron-transfer redox
      reaction from platinum(II) to thallium(III). Vibrational spectra were recorded
      and force constants from normal-coordinate analyses are used for discussing the
      delocalized bonding in these species.

PMID- 11466047
TI  - The utilization of classical spin Monte Carlo methods to simulate the magnetic
      behavior of extended three-dimensional cubic networks incorporating M(II) ions
      with an S = 5/2 ground state spin.
AB  - The numerical simulations of the magnetic properties of extended three
      dimensional networks containing M(II) ions with an S = 5/2 ground-state spin have
      been carried out within the framework of the isotropic Heisenberg model.
      Analytical expressions fitting the numerical simulations for the primitive cubic,
      diamond, together with (10-3) cubic networks have all been derived. With these
      empirical formulas in hands, we can now extract the interaction between the
      magnetic ions from the experimental data for these networks. In the case of the
      primitive cubic network, these expressions are directly compared with those from
      the high-temperature expansions of the partition function. A fit of the
      experimental data for three complexes, namely [(N(CH(3))(4)][Mn(N(3))] 1,
      [Mn(CN(4))](n)() 2, and [Fe(II)(bipy)(3)][Mn(II)(2)(ox)(3)] 3, has been carried
      out. The best fits were those obtained using the following parameters, J = -3.5
      cm(-)(1), g = 2.01 (1); J = -8.3 cm(-)(1), g = 1.95 (2); and J = -2.0 cm(-)(1), g
      = 1.95 (3).

PMID- 11466048
TI  - Synthesis and X-ray characterization of the phosphido-carbonyl cluster anions.
AB  - The [Co(9)P(CO)(21)](2)(-) anion has been isolated from the products of the
      reaction between Na[Co(CO)(4)] and PCl(5) in tetrahydrofuran at reflux. The
      structure of the cluster anion [Co(9)P(CO)(21)](2)(-) in its
      tetraphenylphosphonium salt has been elucidated by X-ray analysis. The crystals
      are monoclinic, space group P2(1)/n, a = 12.528(3), b = 14.711(5), c = 19.312(6)
      A, beta = 93.68(2) degrees, Z = 2. Final R = 0.065 for 2300 unique reflections
      having I > 3sigma(I). The anion, which is disordered about an inversion center,
      consists of a monocapped square antiprismatic cluster containing an interstitial
      phosphide and surrounded by 13 terminal and 8 edge-bridging carbonyl ligands.
      Average values are: Co-Co 2.685 A, and Co-P 2.256 A. The [Co(10)P(CO)(22)](3)(-)
      anion has been obtained by condensation of the [Co(9)P(CO)(21)](2)(-) anion with
      [Co(CO)(4)](-) in tetrahydrofuran at reflux. While the [Co(9)P(CO)(21)](2)(-)
      anion is stable under CO, the [Co(10)P(CO)(22)](3)(-) anion is decomposed to
      [Co(9)P(CO)(21)](2)(-) and [Co(CO)(4)](-). The benzyltrimethylammonium salt of
      the [Co(10)P(CO)(22)](3)(-) anion has been studied by X-ray analysis. It gives
      triclinic crystals, space group P_1, a = 11.452(3), b = 23.510(6), c = 25.606(4)
      A, alpha = 112.46(1), beta = 95.79(1), gamma = 73.548(2) degrees, Z = 4. Final R
      = 0.041 for 8600 unique reflections having I > 3sigma(I). There are two
      independent trianions in the asymmetric unit, both showing similar geometries,
      consisting of bicapped square antiprismatic clusters with a central P atom, each
      bearing 10 terminal and 12 edge-bridging carbonyl ligands, 8 of which, bound to
      the capping metals, are markedly asymmetric. Average values are: Co-Co 2.678 A,
      and Co-P 2.262 A. Electrochemistry shows that [Co(9)P(CO)(21)](2)(-) and
      [Co(10)P(CO)(22)](3)(-) in acetonitrile solution undergo either a one-electron
      oxidation or a two-electron reduction. This latter process appears as a single
      step in the case of the dianion and as two separated one-electron steps in the
      case of the trianion. All the processes are accompanied by slow chemical
      complications, thus testifying that no stable redox congeners exist for these
      phosphide clusters.

PMID- 11466049
TI  - Metallocyclodextrins as building blocks in noncovalent assemblies of photoactive
      units for the study of photoinduced intercomponent processes.
AB  - Cyclodextrin cups have been employed to build supramolecular systems consisting
      of metal and organic photoactive/redox-active components; the photoinduced
      communication between redox-active units assembled in water via noncovalent
      interactions is established. The functionalization of a beta-cyclodextrin with a
      terpyridine unit, ttp-beta-CD, is achieved by protection of all but one of the
      hydroxyl groups by methylation and attachment of the ttp unit on the free primary
      hydroxyl group. The metalloreceptors [(beta-CD-ttp)Ru(ttp)][PF(6)](2), [(beta-CD
      ttp)Ru(tpy)][PF(6)](2), and [Ru(beta-CD-ttp)(2)][PF(6)](2) are synthesized and
      fully characterized. The [(beta-CD-ttp)Ru(ttp)][PF(6)](2) metalloreceptor
      exhibits luminescence in water, centered at 640 nm, from the (3)MLCT state with a
      lifetime of 1.9 ns and a quantum yield of Phi = 4.1 x 10(-)(5). Addition of redox
      active quinone guests AQS, AQC, and BQ to an aqueous solution of [(beta-CD
      ttp)Ru(ttp)](2+) results in quenching of the luminescence up to 40%, 20%, and
      25%, respectively. Measurement of the binding strength indicates that, in
      saturation conditions, 85% for AQS and 77% for AQC are bound. The luminescence
      quenching is attributed to an intercomponent electron transfer from the appended
      ruthenium center to the quinone guest inside the cavity. Control experiments
      demonstrate no bimolecular quenching at these conditions. A photoactive osmium
      metalloguest, [Os(biptpy)(tpy)][PF(6)], is designed with a biphenyl hydrophobic
      tail for insertion in the cyclodextrin cavity. The complex is luminescent at room
      temperature with an emission band maximum at 730 nm and a lifetime of 116 ns. The
      osmium(III) species are formed for the study of photoinduced electron transfer
      upon their assembly with the ruthenium cyclodextrin, [(beta-CD-ttp)Ru(ttp)](2+).
      Time-resolved spectroscopy studies show a short component of 10 ps, attributed to
      electron transfer from Ru(II) to Os(III) giving an electron transfer rate 9.5 x
      10(9) s(-)(1).

PMID- 11466050
TI  - Structural criteria for the rational design of selective ligands. 3. Quantitative
      structure-stability relationship for iron(III) complexation by tris-catecholamide
      siderophores.
AB  - We present an extended MM3 model for catecholamide ligands and their Fe(3+)
      complexes and the application of this model to understand how ligand architecture
      effects Fe(3+) binding affinity. Force field parameters were fit to geometries
      and energies from electronic structure calculations, and to crystal structure
      data. Optimized geometries are reported for phenol, acetamide, the phenol-phenol
      dimer, the acetamide-phenol dimer, and N-methylsalicylamide (HMSA) at the
      BLYP/DZVP2/A2 level of theory. Optimized geometries and relative energies are
      reported for the pseudo-octahedral ground state and the trigonal planar
      transition state of [Fe(CAT)(3)](3)(-) at the VWN/DZVP2/A1 level of theory. The
      MM3 model is validated by comparison of calculated structures with crystal
      structures containing 1,2-dihydroxybenzene (H(2)CAT) and 2,3-dihydroxy-N
      methylbenzamide (H(2)MBA) fragments, crystal structures of [Fe(CAT)(3)](3)(-) and
      tris-catecholamide Fe(3+) complexes, and comparison of MM3 (6.8 kcal/mol) and VWN
      (5.9 kcal/mol) barriers for intramolecular octahedral inversion in
      [Fe(CAT)(3)](3)(-). The MM3 model also rationalizes the higher inversion barrier
      (14 to 18 kcal/mol) reported for [Ga(N,N-diisopropylterephthalamide)(3)](3)(-)
      ([Ga(DIPTA)(3)](3)(-)). Conformational searches were performed on enterobactin
      (H(6)ENT), 1,3,5-tris(2,3-dihydroxybenzamidomethyl)-2,4,6-triethylbenzene
      (H(6)EMECAM), 1,3,5-tris(2,3-dihydroxybenzamidomethyl)-2,4,6-trimethylbenzene
      (H(6)MMECAM), 1,3,5-tris(2,3-dihydroxybenzamidomethyl)benzene (H(6)MECAM), and
      1,5,9-N,N',N' '-tris(2,3-dihydroxybenzoyl)cyclotriazatridecane (H(6)-3,3,4-CYCAM)
      and Fe(3+) complexes with each of these ligands. A conformational search also was
      done on the Fe(3+) complex with the 2,2',2' '-tris(2,3
      dihydroxybenzamido)triethylammonium cation (H(7)TRENCAM(+)). The relationship
      between calculated steric energies and measured thermodynamic quantities is
      discussed, and linear correlations between formation constants and steric energy
      differences are reported. Extrapolation to zero strain predicts formation
      constants 8 +/- 5 orders of magnitude higher than that exhibited by ENT (10(49))
      are possible. This prediction is supported by a formation constant of 10(63)
      estimated from the formation constant of [Fe(2,3-dihydroxy-N,N
      dimethylbenzamide)(3)](3)(-) ([Fe(DMBA)(3)](3)(-)) by considering the entropic
      consequences of connecting three DMBA ligands to a rigid backbone. Structural
      criteria for the identification of improved tris-catecholate ligand architectures
      are presented.

PMID- 11466051
TI  - Characterization of an NH-pi interaction in Co(III) ternary complexes with
      aromatic amino acids.
AB  - The NH-pi interaction has been detected in the crystal structures of Co(III)
      ternary complexes with N,N-bis(carboxymethyl)-(S)-phenylalanine (BCMPA) and
      aromatic amino acids including (S)-phenylalanine ((S)-Phe), (R)-phenylalanine
      ((R)-Phe), and (S)-tryptophan ((S)-Trp)). Additionally, this interaction has been
      studied in solution for Co(III) ternary complexes with BCMPA or NTA (NTA =
      nitrilotriacetic acid) and several amino acids (AA) by means of electronic
      absorption, circular dichroism (CD), and (1)H NMR spectroscopies. The CD
      intensities of the Co(III) complexes with aromatic amino acids measured in the d
      d region ( approximately 20.5 x 10(3) cm(-)(1)) are significantly decreased in
      ethanol solutions relative to water. Analogous complexes with aliphatic amino
      acids do not exhibit this solvent effect. The (1)H NMR spectra of the Co(III)
      complexes with aromatic amino acids measured in DMSO-d(6) exhibit upfield shifts
      of the NH peaks compared with those with aliphatic amino acids, which suggest a
      shielding effect due to the aromaticity. The upshift values coincide with those
      experimentally evaluated from the crystal structures. The magnitude of the
      upfield shifts agrees well with Hammett's rule, indicating that the increase of
      pi-electron densities on the aromatic rings leads attractive NH-pi interaction
      that exerts a larger shielding effect for the NH protons. In ligand-substitution
      reactions of the carbonatocobalt(III) complexes with amino acids, the yields of
      those with aromatic amino acids are higher than the yields obtained for complexes
      with aliphatic amino acids. This observation is discussed in connection with the
      important contribution of the NH-pi interaction as one of the promotion factors
      in the reaction.

PMID- 11466052
TI  - Trinuclear Zn(II) and Cu(II) homo and heterotrimetallic complexes involving D
      glucopyranosyl and biscarboxylate bridging ligands. A substrate binding model of
      xylose isomerases.
AB  - Reactions of MCl(2).nH(2)O with N,N'-bis(D-glucopyranosyl)-1,4,7
      triazacyclononane ((D-Glc)(2)-tacn), which was formed from D-glucose and 1,4,7
      triazacyclononane (tacn) in situ, afforded a series of mononuclear divalent metal
      complexes with two beta-D-glucopyranosyl moieties, [M((D-Glc)(2)-tacn)Cl]Cl (M =
      Zn (11), Cu (12), Ni (13), Co (14)). Complexes 11-14 were characterized by
      analytical and spectroscopic measurements and X-ray crystallography and were
      found to have a distorted octahedral M(II) center ligated by the pentacoordinate
      N-glycoside ligand, (beta-D-glucopyranosyl)(2)-tacn, and a chloride anion. Each D
      glucose moiety is tethered to the metal center through the beta-N-glycosidic bond
      with tacn and additionally coordinated via the C-2 hydroxyl group, resulting in a
      lambda-gauche five-membered chelate ring. When L-rhamnose (6-deoxy-L-mannose) was
      used instead of D-glucose, the nickel(II) complex with two beta-L-rhamnopyranosyl
      moieties, [Ni((D-Man)(2)-tacn)(MeOH)]Cl(2) (15), was obtained and characterized
      by an X-ray analysis. Reactions of 11 (M = Zn) with [Zn(XDK)(H(2)O)] (21) or
      [Cu(XDK)(py)(2)] (22) (H(2)XDK = m-xylylenediamine bis(Kemp's triacid imide))
      yielded homo and heterotrimetallic complexes formulated as [Zn(2)M'((D-Glc)(2)
      tacn)(2)(XDK)]Cl(2) (M' = Zn (31), Cu (32)). The similar reactions of 12 (M = Cu)
      with complex 21 or 22 afforded [Cu(2)M'((D-Glc)(2)-tacn)(2)(XDK)]Cl(2) (M' = Cu
      (33), Zn (34)). An X-ray crystallographic study revealed that complexes 31 and 34
      have either Zn(II)(3) or Cu(II)Zn(II)Cu(II) trimetallic centers bridged by two
      carboxylate groups of XDK and two D-glucopyranosyl residues. The M...M'
      separations are 3.418(3)-3.462(3) A (31) and 3.414(1)-3.460(1) A (34), and the
      M...M'...M angles are 155.18(8) degrees (31) and 161.56(6) degrees (34). The
      terminal metal ions are octahedrally coordinated by the (D-Glc)(2)-tacn ligand
      through three nitrogen atoms of tacn, two oxygen atoms of the C-2 hydroxyl groups
      of the carbohydrates, and a carboxylate oxygen atom of XDK ligand. The central
      metal ions sit in a distorted octahedral environment ligated by four oxygen atoms
      of the carbohydrate residues in the (D-Glc)(2)-tacn ligands and two carboxylate
      oxygen atoms of XDK. The deprotonated beta-D-glucopyranosyl unit at the C-2
      hydroxyl group bridges the terminal and central ions with the C-2 mu-alkoxo
      group, with the C-1 N-glycosidic amino and the C-3 hydroxyl groups coordinating
      to each metal center. Complexes 31-34 are the first examples of metal complexes
      in which D-glucose units act as bridging ligands. These structures could be very
      useful substrate binding models of xylose or glucose isomerases, which promote D
      glucose D-fructose isomerization by using divalent dimetallic centers bridged by
      a glutamate residue.

PMID- 11466053
TI  - Radical-copper wheels: structure and magnetism of hexanuclear hybrid arrays.
AB  - Complexation of copper(II) bromide and chloride with 4-pyrimidinyl nitronyl
      nitroxide (4PMNN) as a bridging ligand gave discrete hexanuclear complexes
      carrying 12 spins, [CuX(2).(4PMNN)](6) [X = Br (1), Cl (2)], which crystallize in
      a trigonal space group. The crystallographic parameters are
      C(11)H(15)Br(2)CuN(4)O(2).0.3H(2)O, a = 28.172(2), c = 12.590(2) A, V = 8653(2)
      A(3), and Z = 18 for 1, and C(11)H(15)Cl(2)CuN(4)O(2).0.3H(2)O, a = 28.261(2), c
      = 12.378(1) A, and Z = 18 for 2. The hexanuclear arrays construct a perfect
      column perpendicular to the molecular plane. The diameter of the resultant
      honeycomblike channel is ca. 11.5 A defined by the interatomic distance of two
      opposing copper ions. Their magnetic behavior is interpreted as the simultaneous
      presence of ferro and antiferromagnetic couplings. The ferromagnetic couplings
      are attributed to the interactions between a copper spin and the axially
      coordinated nitronyl nitroxide spin and between nitronyl nitroxide groups through
      van der Waals contacts. The antiferromagnetic coupling is due to the interaction
      between copper ions across the pyrimidine bridges.

PMID- 11466054
TI  - Excision of uranium oxide chains and ribbons in the novel one-dimensional uranyl
      iodates K(2)[(UO(2))3(IO(3))(4)O(2)] and Ba[(UO(2)2(IO(3))(2)O(2)](H(2)O).
AB  - The alkali metal and alkaline-earth metal uranyl iodates
      K(2)[(UO(2))(3)(IO(3))(4)O(2)] and Ba[(UO(2))(2)(IO(3))(2)O(2)](H(2)O) have been
      prepared from the hydrothermal reactions of KCl or BaCl(2) with UO(3) and
      I(2)O(5) at 425 and 180 degrees C, respectively. While
      K(2)[(UO(2))(3)(IO(3))(4)O(2)] can be synthesized under both mild and
      supercritical conditions, the yield increases from <5% to 73% as the temperature
      is raised from 180 to 425 degrees C. Ba[(UO(2))(2)(IO(3))(2)O(2)](H(2)O),
      however, has only been isolated from reactions performed in the mild temperature
      regime. Thermal measurements (DSC) indicate that K(2)[(UO(2))(3)(IO(3))(4)O(2)]
      is more stable than Ba[(UO(2))(2)(IO(3))(2)O(2)](H(2)O) and that both compounds
      decompose through thermal disproportionation at 579 and 575 degrees C,
      respectively. The difference in the thermal behavior of these compounds provides
      a basis for the divergence of their preparation temperatures. The structure of
      K(2)[(UO(2))(3)(IO(3))(4)O(2)] is composed of [(UO(2))(3)(IO(3))(4)O(2)](2)(-)
      chains built from the edge-sharing UO(7) pentagonal bipyramids and UO(6)
      octahedra. Ba[(UO(2))(2)(IO(3))(2)O(2)](H(2)O) consists of one-dimensional
      [(UO(2))(2)(IO(3))(2)O(2)](2)(-) ribbons formed from the edge sharing of
      distorted UO(7) pentagonal bipyramids. In both compounds the iodate groups occur
      in both bridging and monodentate binding modes and further serve to terminate the
      edges of the uranium oxide chains. The K(+) or Ba(2+) cations separate the chains
      or ribbons in these compounds forming bonds with terminal oxygen atoms from the
      iodate ligands. Crystallographic data: K(2)[(UO(2))(3)(IO(3))(4)O(2)], triclinic,
      space group P_1, a = 7.0372(5) A, b = 7.7727(5) A, c = 8.9851(6) A, alpha =
      93.386(1) degrees, beta = 105.668(1) degrees, gamma = 91.339(1) degrees, Z = 1;
      Ba[(UO(2))(2)(IO(3))(2)O(2)](H(2)O), monoclinic, space group P2(1)/c, a =
      8.062(4) A, b = 6.940(3) A, c = 21.67(1), beta= 98.05(1) degrees, Z = 4.

PMID- 11466055
TI  - Estrogen-derived steroidal metal complexes: agents for cellular delivery of metal
      centers to estrogen receptor-positive cells.
AB  - Targeted cellular delivery of drugs to specific tissues is an important goal in
      biomedical chemistry. Achieving this requires harnessing and applying molecular
      level recognition events prevalent in (or specific to) the desired tissue type.
      Tissues rich in estrogen receptors (ERs), which include many types of breast
      cancer, accumulate molecules that have high binding affinities for these
      receptors. Therefore, molecules that (i) bind to the ER, (ii) have favorable
      cellular transport properties, and (iii) contain a second functionality (such as
      a center that may be used for diagnostic imaging or medical therapy) are exciting
      synthetic targets in the field of drug delivery. To this end, we have prepared a
      range of metallo-estrogens based on 17alpha-ethynylestradiol and examined their
      binding to the ER both as isolated receptor and in whole cell assays (ER positive
      MCF-7 cells). Estrogens functionalized with metal binding units are prepared by
      palladium-catalyzed cross-coupling reactions and a wide range of metal centers
      introduced readily. All the compounds prepared and tested exhibit effective
      binding to the estrogen receptor and are delivered across the cell membrane into
      MCF-7 cells. In the whole cell assays, despite their monocationic nature, the
      palladium and platinum complexes prepared exhibit similar (and even enhanced)
      receptor binding affinities compared to their corresponding neutral free ligands.
      It is unprecedented for a higher ER binding affinity to be observed for a
      cationic complex than for its metal-free ligand.

PMID- 11466056
TI  - An investigation of the lead(II)-hydroxide system.
AB  - A detailed investigation of the Pb(II)/OH(-) system has been made in NaClO(4)
      media at 25 degrees C. Combined UV-vis spectrophotometric-potentiometric
      titrations at [Pb(II)](T) < or = 10 microM using a long path length cell detected
      only four mononuclear hydroxide complexes. The values of log beta(1)(q)(), for
      the equilibria Pb(2+)(aq) + qH(2)O <--> Pb(OH)(q)()((2)(-)(q)()()+)(aq) +
      qH(+)(aq), were -7.2, -16.1, -26.5, and -38.0 for q = 1-4, respectively, at ionic
      strength I = 1 M (NaClO(4)). Similar results were obtained at I = 5 M (NaClO(4)).
      No evidence was found for higher order complexes (q > 4) even at very high [OH(
      )]/[Pb(II)] ratios, nor for polynuclear species at [Pb(II)](T) < or = 10 microM.
      Measurements using (207)Pb-NMR and Raman spectroscopies and differential pulse
      polarography (DPP) provided only semiquantitative confirmation. The mononuclear
      Pb(OH)(q)()((2)(-)(q)()()+)(aq) complexes are the only hydrolyzed species likely
      to be significant under typical environmental and biological conditions.

PMID- 11466057
TI  - Structures and conformations of trifluoromethyl fluoroformate and
      perfluorodimethyl carbonate.
AB  - The conformational properties and geometric structures of trifluoromethyl
      fluoroformate, CF(3)OC(O)F (1), and perfluorodimethyl carbonate, (CF(3)O)(2)CO
      (2), have been studied by matrix IR spectroscopy, gas electron diffraction (GED),
      and quantum chemical calculations (MP2 and B3LYP with 6-311G basis sets). In both
      compounds the synperiplanar orientation of the O-CF(3) groups relative to the C=O
      double bond is preferred. If heated Ar/1 and Ar/2 mixtures are deposited as a
      matrix at 14 K, new bands appear in the matrix IR spectra which are assigned to
      the anti form of 1 and to the syn/anti form of 2. At room temperature the
      contribution of the anti rotamer of 1 is 4% (DeltaH degrees = H degrees (anti) -
      H degrees (syn) = 1.97(5) kcal/mol), and the contribution of the syn/anti
      conformer of 2 is estimated to be less than 1%. These high-energy conformers are
      not observed in the GED experiment. The quantum chemical calculations reproduce
      the structural and conformational properties of both compounds satisfactorily.

PMID- 11466058
TI  - Light- and thermal-induced spin crossover in [Fe(abpt)2(N(CN)2)2]. Synthesis,
      structure, magnetic properties, and high-spin<-->low spin relaxation studies.
AB  - [Fe(abpt)2(N(CN)2)2] (abpt = 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole)
      represents the first example of an iron(II) spin-crossover compound containing
      dicyanamide ligand, [N(CN)(2)](-), as a counterion. It shows an incomplete two
      step spin transition with around 37% of HS molecules trapped in the low
      temperature region when standard cooling or warming modes, i.e., 1-2 K min(-)(1),
      were used. The temperature, T(1/2) approximately 86 K, at which 50% of the
      conversion takes place, is one of the lowest temperatures observed for an
      iron(II) spin-crossover compound. Quenching experiments at low temperatures have
      shown that the incomplete character of the conversion is a consequence of slow
      kinetics. The quenched HS state relaxes back to the LS state displaying
      noticeable deviation from a single-exponential law. The rate of relaxation was
      evaluated in the range of temperatures 10-60 K. In the upper limit of
      temperatures, where thermal activation predominates, the activation energy and
      the pre-exponential parameter were estimated as E(a) approximately 280 cm(-)(1)
      and A(HL) approximately 10 s(-)(1), respectively. The lowest value of k(HL)
      around 1.2 x 10(-)(4) s(-)(1) (T = 10 K) was obtained in the region of
      temperatures where tunneling predominates. A quantitative light induced excited
      spin state trapping (LIESST) effect was observed, and the HS --> LS relaxation in
      the range of temperatures 5-52.5 K was studied. From the Arrhenius plot the two
      above-mentioned characteristic regimes, thermal-activated (E(a) approximately 431
      cm(-)(1) and A(HL) approximately 144 s(-)(1)) and tunneling (k(HL) approximately
      1.7 x 10(-)(6) s(-)(1) at 5 K), were characterized. The crystal structure was
      solved at room temperature. It crystallizes in the triclinic P_1 space group, and
      the unit cell contains a centrosymmetric mononuclear unit. Each iron atom is in a
      distorted octahedral environment with bond distances Fe-N(1) = 2.216(2) A, Fe
      N(2) = 2.121(2) A, and Fe-N(3) = 2.160(2) A for the pyridine, triazole, and
      dicyanamide ligands, respectively.

PMID- 11466059
TI  - Group 5 imido complexes derived from diamido-pyridine ligands.
AB  - Reaction of the vanadium(V) imide [V(NAr)Cl(3)(THF)] (Ar = 2,6
      C(6)H(3)(i)()Pr(2)) with the diamino-pyridine derivative MeC(2
      C(5)H(4)N)(CH(2)NHSiMe(2)(t)()Bu)(2) (abbreviated as H(2)N'(2)N(py)) gave modest
      yields of the vanadium(IV) species [V(NAr)(H(3)N'N' 'N(py))Cl(2)] (1 where
      H(3)N'N' 'N(py) = MeC(2- C(5)H(4)N)(CH(2)NH(2))(CH(2)NHSiMe(2)(t)()Bu) in which
      the original H(2)N'(2)N(py) has effectively lost SiMe(2)(t)()Bu (as
      ClSiMe(2)(t)()Bu) and gained an H atom. Better behaved reactions were found
      between the heavier Group 5 metal complexes [M(NR)Cl(3)(py)(2)] (M = Nb or Ta, R
      = (t)()Bu or Ar) and the dilithium salt Li(2)[N(2)N(py)] (where H(2)N(2)N(py) =
      MeC(2-C(5)H(4)N)(CH(2)NHSiMe(3))(2)), and these yielded the six-coordinate M(V)
      complexes [M(NR)Cl(N(2)N(py))(py)] (M = Nb, R = (t)()Bu 2; M = Ta, R = (t)()Bu 3
      or Ar 4). The compounds 2-4 are fluxional in solution and undergo dynamic
      exchange processes via the corresponding five-coordinate homologues
      [M(NR)Cl(N(2)N(py))]. Activation parameters are reported for the complexes 2 and
      3. In the case of 2, high vacuum tube sublimation afforded modest quantities of
      [Nb(N(t)()Bu)Cl(N(2)N(py))] (5). The X-ray crystal structures of the four
      compounds 1, 2, 3, and 4 are reported.

PMID- 11466060
TI  - Automated synthesis of 3'-metalated oligonucleotides.
AB  - We report the first synthesis of a metallonucleoside bound to a solid support and
      subsequent oligonucleotide synthesis with this precursor. Large-scale syntheses
      of metal-containing oligonucleotides are achieved using a solid support modified
      with [Ru(bpy)(2)(impy')](2+) (bpy is 2,2'-bipyridine; impy' is 2'
      iminomethylpyridyl-2'-deoxyuridine). A duplex formed with the metal-containing
      oligonucleotide exhibits superior thermal stability when compared to the
      corresponding unmetalated duplex (T(m) = 50 degrees C vs T(m) = 48 degrees C).
      Electrochemical (E(1/2) = 1.3 V vs NHE), absorption (lambda(max) = 480 nm), and
      emission (lambda(max) = 720 nm, tau = 44 ns, Phi = 0.11 x 10(-)(3)) data for the
      ruthenium-modified oligonucleotides indicate that the presence of the
      oligonucleotide does not perturb the electronic properties of the ruthenium
      complex. The absence of any change in the emission properties upon duplex
      formation suggests that the [Ru(bpy)(2)(impy)](2+) chromophore will be a valuable
      probe for DNA-mediated electron-transfer studies. Despite the relatively high
      Ru(III/II) reduction potential, oxidative quenching of photoexcited
      [Ru(bpy)(2)(impy)](2+) does not lead to oxidative damage of guanine or other DNA
      bases.

PMID- 11466061
TI  - Comparative study of NS(2)(S-aryl) pyridine-based dithia-containing ligands with
      different substituent groups. Reactivity toward Cu(II) and Ru(II).
AB  - Ligands LX of the type NS(2) with S-aryl substituents which incorporate the unit
      2,6-bis(thiomethyl)pyridine modified with functional groups bonded to the
      aromatic moieties, either on the phenyl or on the pyridine, are produced.
      Electron-withdrawing groups, 3-chloro and 4-nitro, that reduce the pyridine
      basicity have been introduced. Methoxy or methoxycarbonyl substituents have been
      incorporated on the thiophenyl moieties. The comparative results from the
      reaction of these ligands with Cu(ClO(4))(2).6H(2)O and [RuCl(2)(PPh(3))(3)] have
      revealed that their coordination capacity has not been greatly modified as a
      result of the introduced groups. Complexes of general formulas
      [Cu(LX)][ClO(4)](2), except for L5, and [RuCl(2)(LX)(PPh(3))], have been
      obtained, respectively. The electronic characteristics of these complexes have
      been studied by cyclic voltammetry experiments. The structures of 2,6-bis[(2'
      methoxycarbonyl)phenylthio-methyl]-4-nitropyridine (L5) and
      [RuCl(2)(L5)(PPh(3))].2CCl(4) have been characterized by single-crystal X-ray
      diffraction methods.

PMID- 11466062
TI  - Platinum(II) hydrazido complexes.
AB  - Reaction of 1,2-dimethylhydrazine with the platinum hydroxo complex [(dppp)Pt(mu
      OH)](2)(BF(4))(2) gives the bridging 1,2-dimethylhydrazido(-2) product
      [(dppp)(2)Pt(2)(mu-eta(2):eta(2)-MeNNMe)](BF(4))(2) 1. Crystals of 1.CH(2)Cl(2)
      from CH(2)Cl(2)/Et(2)O are monoclinic (C/2) with a = 19.690(1), b = 18.886(1), c
      = 17.170 (1) A, and beta = 92.111(1) degrees. Treatment of [(dppp)Pt(mu
      OH)](2)(OTf)(2) with 1,1-dimethylhydrazine gives [(dppp)(2)Pt(2)(mu-OH)(mu
      NHNMe(2))](OTf)(2) 2. Crystals of 2.CH(2)Cl(2) from CH(2)Cl(2)/Et(2)O are
      triclinic (P-1) with a = 12.910 (3), b = 13.927(3), c = 17.5872 (3) A, alpha =
      87.121(3), beta = 89.997(4), and gamma = 84.728(3) degrees. Reaction of
      [(dppp)Pt(mu-OH)](2)(OTf)(2) with 1 equiv of phenylhydrazine in CH(2)Cl(2) gives
      [(dppp)(2)Pt(2)(mu-OH)(mu-NHNHPh)](OTf)(2) 3. Two equivalents of phenylhydrazine
      with [(dppp)Pt(mu-OH)](2)(X)(2) gives [(dppp)Pt(mu-NHNHPh)](2)(X)(2) 4 (X =
      BF(4), OTf). Crystals of 3.ClCH(2)CH(2)Cl from ClCH(2)CH(2)Cl/(i)()Pr(2)O are
      monoclinic (P2(1)/n) with a = 20.990(2), b = 13.098(1), c = 25.773 (2) A, and
      beta = 112.944(2) degrees. Crystals of 4(X =
      BF(4)).ClCH(2)CH(2)Cl(.)()2((t)()BuOMe) from ClCH(2)CH(2)Cl/(t)()BuOMe are
      monoclinic (C2/m) with a = 30.508(1), b = 15.203(1), c = 19.049 (1) A, and beta =
      118.505(2) degrees.

PMID- 11466063
TI  - Sulfur-rich zinc chemistry: new tris(thioimidazolyl)hydroborate ligands and their
      zinc complex chemistry related to the structure and function of alcohol
      dehydrogenase.
AB  - The 1-substituted tris(2-thioimidazolyl)hydroborate ligands Tt(R) were prepared
      as the potassium salts from KBH(4) and the corresponding 1-R-2-thioimidazole for
      R = t-Bu and C(6)H(4)-p-CH(CH(3))(2) (Cum). Their reactions with zinc salts
      yielded the tetrahedral complexes Tt(R)Zn-X with X = F, Cl, ONO(2) and (Tt(t)()(
      )(Bu))(2)Zn. With zinc perchlorate the labile perchlorate complexes Tt(R)Zn
      OClO(3) were obtained. They served as starting materials for the incorporation of
      substrates which are relevant for the chemistry of horse liver alcohol
      dehydrogenase: Ethanol led to [Tt(t)()(-Bu)Zn.EtOH] ClO(4).EtOH, p-nitrophenol
      (NitOH) yielded Tt(Cum)Zn-ONit. Pyridine-2-carbaldehyde and salicylic aldehyde
      were incorporated as N(pyridine) and O(phenolate) coligands with possible
      additional O(aldehyde) coordination. Substituted pyridyl methanols (R-PyCH(2)OH)
      yielded the trinuclear complexes [(Tt(t)()(-Bu))(2)Zn(3)(R-PyCH(2)O)(2)]
      (ClO(4))(2) with bridging Tt and pyridylmethoxide ligands. Preliminary
      experiments on the functional modeling of alcohol dehydrogenase have shown that
      TtZn complexes promote both the dehydrogenation of 2-propanol and the
      hydrogenation of pentafluorobenzaldehyde.

PMID- 11466064
TI  - Solvent (1)H NMRD study of hexaaquochromium(III): inferences on hydration and
      electron relaxation.
AB  - The water proton nuclear magnetic relaxation dispersions (NMRD) of
      hexaaquochromium(III) in water and in water-glycerol solutions were obtained at
      several temperatures and viscosities. The data were analyzed in terms of the
      available theories by taking into account the contributions from first sphere,
      second sphere, and outer sphere water molecules. A meaningful analysis was
      possible by taking advantage of the structural model obtained from (17)O
      relaxation data, which was recently made available in the literature (Bleuzen,
      A.; Foglia, F.; Furet, E.; Helm, L.; Merbach, A.; Weber, J. J. Am. Chem. Soc.
      1996, 118, 12 777). Dynamic parameters, like the molecular rotational time, the
      exchange time of the water protons of the first coordination sphere, the
      correlation time for electron relaxation, and the magnetic field dependence of
      electron relaxation were obtained. The possible contribution to water proton
      relaxivity of second sphere water molecules for some other hexaaqua complexes is
      also discussed.

PMID- 11466065
TI  - Structural, magnetic and catalytic properties of a self-recognized mu-oxo-bridged
      diiron(III) bis(benzimidazole) complex.
AB  - The inherent nonplanarity and C(2) symmetry of the dimethyl-substituted
      bis(benzimidazole) ligand (Me(2)BBZ) results in two distinct atropisomers that,
      when separated, have been suggested to have potential for chiral recognition and
      catalysis. Here is reported the synthesis and characterization of a diiron mu-oxo
      bridged bis(benzimidazole) complex, 1, that provides indirect support for this
      hypothesis. Dimerization of a racemic solution of iron-Me(2)BBZ monomers via the
      mu-oxo bridge yields (+,+) and (-,-) diastereomers whose complementary
      association can be attributed to the inherent sidedness of the metal-Me(2)BBZ
      interaction surface, and to the differences in the torsional angles of the
      phenyl(benzimidazole) units (34 degrees) and the Schiff base linkages (54
      degrees). These results highlight the steric differences between the
      phenyl(benzimidazole) and Schiff-base portions of the ligand, features that could
      be important in the chiral recognition of ligands and in differentiating
      substrate trajectories as required for asymmetric catalysis. For completeness,
      studies of 1 in the catalytic epoxidation of styrene are also reported.

PMID- 11466066
TI  - (Salen)Mn(III)-catalyzed epoxidation reaction as a multichannel process with
      different spin states. Electronic tuning of asymmetric catalysis: a theoretical
      study.
AB  - The (salen)Mn(III)-catalyzed epoxidation reaction mechanism has been investigated
      using density functional theory (DFT). There is considerable interest in and
      controversy over the mechanism of this reaction. The results of experimental
      studies have offered some support for three different reaction mechanisms:
      concerted, stepwise radical, and metallooxetane mediated. In this paper, a
      theoretical examination of the reaction suggests a novel mechanism that describes
      the reaction as a multichannel process combining both concerted and stepwise
      radical pathways. The competing channels have different spin states: the singlet,
      the triplet, and the quintet. The singlet reaction pathway corresponds to a
      concerted mechanism and leads exclusively to a cis epoxide product. In contrast,
      the triplet and quintet reactions follow a stepwise mechanism and lead to a
      product mixture of cis and trans epoxides. We show that the experimentally
      observed dependence of isomer product ratios on electronic effects connected with
      the substitution of the catalyst ligands is due to changing the relative position
      and, hence, the relative activities of the channels with different cis-trans
      yields. Because the results and conclusions of the present work dramatically
      differ from the results and conclusion of the recent DFT theoretical
      investigation (Linde, C.; Akermark, B; Norrby, P.-O.; Svensson, M. J. Am. Chem.
      Soc. 1999, 121, 5083.), we studied possible sources for the deep contradictions
      between the two works. The choice of the DFT functional and a model has been
      shown to be crucial for accurate results. Using high level ab initio calculations
      (coupled cluster-CCSD(T)), we show that the computational procedure employed in
      this study generates significantly more reliable numerical results. It is also
      shown that the smaller cationic model without a chlorine ligand that was used by
      Linde et al. is too oversimplified with respect to our larger neutral model. For
      this reason, using the cationic model led to a qualitatively wrong quintet
      reaction profile that played a key role in theoretical postulates in the earlier
      work.

PMID- 11466067
TI  - Synthesis, structural characterization, and transmetalation reactions of a
      tetranuclear magnesium silsesquioxane complex.
AB  - The reaction of a silsesquioxane trisilanol with methylmagnesium chloride leads
      to an unprecedented tetranuclear magnesium silsesquioxane complex 1 in high
      yield. The crystal structure shows an unusually short Mg-Cl bond, indicative of
      an electron-deficient magnesium atom; 1 has been used as transmetalation agent
      for the synthesis of metal silsesquioxane complexes. Transmetalation activity was
      low, but can easily be followed by multinuclear NMR. Crystal data for 1:
      C(78)H(142)Cl(2)Mg(4)O(26)Si(14).6(C(4)H(8)O), a = 15.744(1) A, b = 26.526(2) A,
      c = 16.917(1) A, beta = 113.229(2) degrees, monoclinic, P2(1)/n, Z = 2.

PMID- 11466068
TI  - Photophysics of diimine platinum(II) bis-acetylide complexes.
AB  - A comprehensive photophysical investigation has been carried out on a series of
      eight complexes of the type (diimine)Pt(-C=C-Ar)(2), where diimine is a series of
      2,2'-bipyridine (bpy) ligands and -C=C-Ar is a series of substituted aryl
      acetylide ligands. In one series of complexes, the energy of the Pt --> bpy metal
      to-ligand charge transfer (MLCT) excited state is varied by changing the
      substituents on the 4,4'- and/or the 5,5'-positions of the bpy ligand. In a
      second series of complexes the electronic demand of the aryl acetylide ligand is
      varied by changing the para substituent (X) on the aryl ring (X = -CF(3), -CH(3),
      -OCH(3), and -N(CH(3))(2)). The effect of variation of the substituents on the
      excited states of the complexes has been assessed by examining their UV-visible
      absorption, variable-temperature photoluminescence, transient absorption, and
      time-resolved infrared spectroscopy. In addition, the nonradiative decay rates of
      the series of complexes are subjected to a quantitative energy gap law analysis.
      The results of this study reveal that in most cases the photophysics of the
      complexes is dominated by the energetically low lying Pt --> bpy (3)MLCT state.
      Some of the complexes also feature a low-lying intraligand (IL) (3)pi,pi excited
      state that is derived from transitions between pi- and pi-type orbitals localized
      largely on the aryl acetylide ligands. The involvement of the IL (3)pi,pi state
      in the photophysics of some of the complexes is signaled by unusual features in
      the transient absorption, time-resolved infrared, and photoluminescence spectra
      and in the excited-state decay kinetics. The time-resolved infrared difference
      spectroscopy indicates that Pt --> bpy MLCT excitation induces a +25 to + 35 cm(
      )(1) shift in the frequency of the C=C stretching band. This is the first study
      to report the effect of MLCT excitation on the vibrational frequency of an
      acetylide ligand.

PMID- 11466069
TI  - New Ru(II) chromophores with extended excited-state lifetimes.
AB  - We describe the synthesis, electrochemical, and photophysical properties of two
      new luminescent Ru(II) diimine complexes covalently attached to one and three 4
      piperidinyl-1,8-naphthalimide (PNI) chromophores, [Ru(bpy)(2)(PNI
      phen)](PF(6))(2) and [Ru(PNI-phen)(3)](PF(6))(2), respectively. These compounds
      represent a new class of visible light-harvesting Ru(II) chromophores that
      exhibit greatly enhanced room-temperature metal-to-ligand charge transfer (MLCT)
      emission lifetimes as a result of intervening intraligand triplet states ((3)IL)
      present on the pendant naphthalimide chromophore(s). In both Ru(II) complexes,
      the intense singlet fluorescence of the pendant PNI chromophore(s) is nearly
      quantitatively quenched and was found to sensitize the MLCT-based
      photoluminescence. Excitation into either the (1)IL or (1)MLCT absorption bands
      results in the formation of both (3)MLCT and (3)IL excited states, conveniently
      monitored by transient absorption and fluorescence spectroscopy. The relative
      energy ordering of these triplet states was determined using time-resolved
      emission spectra at 77 K in an EtOH/MeOH glass where dual emission from both
      Ru(II) complexes was observed. Here, the shorter-lived higher energy emission has
      a spectral profile consistent with that typically observed from (3)MLCT excited
      states, whereas the millisecond lifetime lower energy band was attributed to
      (3)IL phosphorescence of the PNI chromophore. At room temperature the data are
      consistent with an excited-state equilibrium between the higher energy (3)MLCT
      states and the lower energy (3)PNI states. Both complexes display MLCT-based
      emission with room-temperature lifetimes that range from 16 to 115 micros
      depending upon solvent and the number of PNI chromophores present. At 77 K it is
      apparent that the two triplet states are no longer in thermal equilibrium and
      independently decay to the ground state.

PMID- 11466070
TI  - Addition of diphenylacetylene to MoO(2)S(2)(2-) in NH(3)-CH(3)OH medium.

PMID- 11466071
TI  - 2D molecular square grid with strong blue fluorescent emission: a complex of
      norfloxacin with zinc(II).

PMID- 11466072
TI  - Synthesis and single crystal investigation of two-dimensional rectangular network
      [M(4,4'-bpy)(Phth)(H(2)O)]n.2H(2)O with small neutral cavities.

PMID- 11466073
TI  - Dihydrobis(4-cyano-3-phenylpyrazol-1-yl)borate: homoleptic mononuclear cobalt(II)
      and copper(II) complexes with a cyano-substituted scorpionate ligand.

PMID- 11466074
TI  - Unusual transformation of n-arylbenzohydroxamic acids mediated by osmium.
      Formation of organometallic complexes of osmium(III).

PMID- 11466075
TI  - Comparison of metal-metal electronic interactions in an isomeric pair of
      dinuclear ruthenium complexes with different bridging pathways: effective hole
      transfer through a bis-phenolate bridge.

PMID- 11466078
TI  - Physician-astronauts have pioneered during two decades of shuttle flights.

PMID- 11466079
TI  - Many say adult stem cell reports overplayed.

PMID- 11466083
TI  - Health agencies update. HIV and heroin interactions.

PMID- 11466085
TI  - From the Surgeon General. International tobacco control: an update.

PMID- 11466086
TI  - The pharmaceutical industry and continuing education.

PMID- 11466087
TI  - The pharmaceutical industry and continuing education.

PMID- 11466088
TI  - The pharmaceutical industry and continuing education.

PMID- 11466089
TI  - The pharmaceutical industry and continuing education.

PMID- 11466091
TI  - Negative outcomes of infant home apnea monitoring.

PMID- 11466093
TI  - Regulations governing the use of laboratory animals.

PMID- 11466094
TI  - Regulations governing the use of laboratory animals.

PMID- 11466095
TI  - Regulations governing the use of laboratory animals.

PMID- 11466096
TI  - Right heart catheterization and cardiac complications in patients undergoing
      noncardiac surgery: an observational study.
AB  - CONTEXT: Right heart catheterization (RHC) is commonly performed before high-risk
      noncardiac surgery, but the benefit of this strategy remains unproven. OBJECTIVE:
      To evaluate the relationship between use of perioperative RHC and postoperative
      cardiac complication rates in patients undergoing major noncardiac surgery.
      DESIGN: Prospective, observational cohort study. SETTING: Tertiary care teaching
      hospital in the United States. PATIENTS: Patients (n = 4059 aged >/=50 years) who
      underwent major elective noncardiac procedures with an expected length of stay of
      2 or more days between July 18, 1989, and February 28, 1994. Two hundred twenty
      one patients had RHC and 3838 did not. MAIN OUTCOME MEASURE: Combined end point
      of major postoperative cardiac events, including myocardial infarction, unstable
      angina, cardiogenic pulmonary edema, ventricular fibrillation, documented
      ventricular tachycardia or primary cardiac arrest, and sustained complete heart
      block, classified by a reviewer blinded to preoperative data. RESULTS: Major
      cardiac events occurred in 171 patients (4.2%). Patients who underwent
      perioperative RHC had a 3-fold increase in incidence of major postoperative
      cardiac events (34 [15.4%] vs 137 [3.6%]; P<.001). In multivariate analyses, the
      adjusted odds ratios (ORs) for postoperative major cardiac and noncardiac events
      in patients undergoing RHC were 2.0 (95% confidence interval [CI], 1.3-3.2) and
      2.1 (95% CI, 1.2-3.5), respectively. In a case-control analysis of a subset of
      215 matched pairs of patients who did and did not undergo RHC, adjusted for
      propensity of RHC and type of procedure, patients who underwent perioperative RHC
      also had increased risk of postoperative congestive heart failure (OR, 2.9; 95%
      CI, 1.4-6.2) and major noncardiac events (OR, 2.2; 95% CI, 1.4-4.9). CONCLUSIONS:
      No evidence was found of reduction in complication rates associated with use of
      perioperative RHC in this population. Because of the morbidity and the high costs
      associated with RHC, the impact of this intervention in perioperative care should
      be evaluated in randomized trials.

PMID- 11466097
TI  - Analgesic use and renal function in men.
AB  - CONTEXT: Several case-control studies suggest an association between analgesic
      use and increased risk of chronic renal disease, but few cohort studies have
      examined this association. OBJECTIVE: To determine whether analgesic use is
      associated with risk of renal dysfunction. DESIGN AND SETTING: Cohort study of
      analgesic use data from the Physicians' Health Study, which lasted 14 years from
      September 1982 to December 1995 with annual follow-up. PARTICIPANTS: A total of
      11 032 initially healthy men who provided blood samples and self-report of
      analgesic use. MAIN OUTCOME MEASURES: Elevated creatinine level defined as 1.5
      mg/dL (133 micromol/L) or higher and a reduced creatinine clearance defined as 55
      mL/min (0.9 mL/s) or less, and self-reported use of acetaminophen, aspirin, and
      other nonsteroidal anti-inflammatory drugs (never [<12 pills]; 12-1499 pills;
      1500-2499 pills; and >/=2500 pills). RESULTS: A total of 460 men had elevated
      creatinine levels (4.2%) and 1258 had reduced creatinine clearance (11.4%). Mean
      creatinine levels and creatinine clearances were similar among men who did not
      use analgesics and those who did, even at total intakes of 2500 or more pills. In
      multivariable analyses adjusted for age; body mass index; history of
      hypertension, elevated cholesterol, and diabetes; occurrence of cardiovascular
      disease; physical activity; and use of other analgesics, the relative risks of
      elevated creatinine level associated with intake of 2500 or more pills were 0.83
      (95% confidence interval [CI], 0.50-1.39; P for trend =.05) for acetaminophen,
      0.98 (95% CI, 0.53-1.81; P for trend =.96) for aspirin, and 1.07 (95% CI, 0.71
      1.64; P for trend =.86) for other nonsteroidal anti-inflammatory drugs. No
      association was observed between analgesic use and reduced creatinine clearance.
      CONCLUSIONS: Moderate analgesic use in this cohort study of initially healthy men
      was not associated with increased risk of renal dysfunction.

PMID- 11466098
TI  - Pacifier use, early weaning, and cry/fuss behavior: a randomized controlled
      trial.
AB  - CONTEXT: The World Health Organization and the United Nations Children's Fund
      strongly discourage use of pacifiers because of their perceived interference with
      breastfeeding. Observational studies have reported a strong association between
      pacifier use and early weaning, but such studies are unable to determine whether
      the association is causal. OBJECTIVES: To test whether regular pacifier use is
      causally related to weaning by 3 months postpartum and to examine differences in
      results according to randomized intervention allocation vs observational use or
      nonuse of pacifiers. DESIGN: Double-blind, randomized controlled trial conducted
      from January 1998 to August 1999. SETTING: Postpartum unit of a university
      teaching hospital in Montreal, Quebec. PARTICIPANTS: A total of 281 healthy,
      breastfeeding women and their healthy, term singleton infants. INTERVENTIONS:
      Participants were randomly allocated to 1 of 2 counseling interventions provided
      by a research nurse trained in location counseling. The experimental intervention
      (n = 140) differed from the control (n = 141) by recommending avoidance of
      pacifier use and suggesting alternative ways to comfort a crying or fussing
      infant. MAIN OUTCOME MEASURES: Early weaning, defined as weaning within the first
      3 months, compared between groups; 24-hour infant behavior logs detailing
      frequency and duration of crying, fussing, and pacifier use at 4, 6, and 9 weeks.
      RESULTS: A total of 258 mother-infant pairs (91.8%) completed follow-up. The
      experimental intervention increased total avoidance of pacifier use (38.6% vs
      16.0% in the control group), reduced daily use (40.8% vs 55.7%), and decreased
      the mean number of pacifier insertions per day (0.8 vs 2.4 at 4 weeks [P<.001];
      0.8 vs 3.0 at 6 weeks [P<.001]; and 1.3 vs 3.0 at 9 weeks [P =.004]). In the
      analysis based on randomized intervention allocation, the experimental
      intervention had no discernible effect on weaning at 3 months (18.9% vs 18.3% in
      the experimental vs control group; relative risk [RR], 1.0; 95% confidence
      interval [CI], 0.6-1.7), and no effect was observed on cry/fuss behavior (in the
      experimental vs control groups, respectively, total daily duration, 143 vs 151
      minutes at 4 weeks [P =.49]; 128 vs 131 minutes at 6 weeks [P =.81]; and 110 vs
      104 minutes at 9 weeks [P =.58]). When randomized allocation was ignored,
      however, we observed a strong observational association between exposure to daily
      pacifier use and weaning by 3 months (25.0% vs 12.9% of the exposed vs unexposed
      groups; RR, 1.9; 95% CI, 1.1-3.3). CONCLUSIONS: We found a strong observational
      association between pacifier use and early weaning. No such association was
      observed, however, when our data were analyzed by randomized allocation, strongly
      suggesting that pacifier use is a marker of breastfeeding difficulties or reduced
      motivation to breastfeed, rather than a true cause of early weaning.

PMID- 11466099
TI  - C-reactive protein, interleukin 6, and risk of developing type 2 diabetes
      mellitus.
AB  - CONTEXT: Inflammation is hypothesized to play a role in development of type 2
      diabetes mellitus (DM); however, clinical data addressing this issue are limited.
      OBJECTIVE: To determine whether elevated levels of the inflammatory markers
      interleukin 6 (IL-6) and C-reactive protein (CRP) are associated with development
      of type 2 DM in healthy middle-aged women. DESIGN: Prospective, nested case
      control study. SETTING: The Women's Health Study, an ongoing US primary
      prevention, randomized clinical trial initiated in 1992. PARTICIPANTS: From a
      nationwide cohort of 27 628 women free of diagnosed DM, cardiovascular disease,
      and cancer at baseline, 188 women who developed diagnosed DM over a 4-year follow
      up period were defined as cases and matched by age and fasting status with 362
      disease-free controls. MAIN OUTCOME MEASURES: Incidence of confirmed clinically
      diagnosed type 2 DM by baseline levels of IL-6 and CRP. RESULTS: Baseline levels
      of IL-6 (P<.001) and CRP (P<.001) were significantly higher among cases than
      among controls. The relative risks of future DM for women in the highest vs
      lowest quartile of these inflammatory markers were 7.5 for IL-6 (95% confidence
      interval [CI], 3.7-15.4) and 15.7 for CRP (95% CI, 6.5-37.9). Positive
      associations persisted after adjustment for body mass index, family history of
      diabetes, smoking, exercise, use of alcohol, and hormone replacement therapy;
      multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6
      (95% CI, 0.9-5.6; P for trend =.07) and 4.2 for CRP (95% CI, 1.5-12.0; P for
      trend =.001). Similar results were observed in analyses limited to women with a
      baseline hemoglobin A(1c) of 6.0% or less and after adjustment for fasting
      insulin level. CONCLUSIONS: Elevated levels of CRP and IL-6 predict the
      development of type 2 DM. These data support a possible role for inflammation in
      diabetogenesis.

PMID- 11466100
TI  - Relationship between methodological trial quality and the effects of selective
      digestive decontamination on pneumonia and mortality in critically ill patients.
AB  - CONTEXT: Although meta-analyses of randomized trials have shown that selective
      digestive decontamination (SDD) prevents nosocomial pneumonia in critically ill
      patients, the influence of trial quality on the effectiveness of SDD has not been
      rigorously evaluated. OBJECTIVE: To assess the methodological quality of
      individual studies of SDD and its relation to the reported effects on pneumonia
      and mortality. DESIGN: Thirty-two studies were identified in a MEDLINE and
      reference list search and their methodological quality was assessed using a
      scoring system (range, 0-13 points) based on allocation and concealment, patient
      selection, patient characteristics, blinding of the intervention, and the
      definition of pneumonia. MAIN OUTCOME MEASURE: Methodological quality of the
      primary trials and its effect on the relative risk reductions (RRRs) of SDD on
      pneumonia and mortality. RESULTS: The mean (SD) methodological quality score was
      7.8 (2.9) (range, 1-11). The RRRs ranged from -0.1 to 1.0 for pneumonia and from 
      0.1 to 0.6 for mortality. The methodological quality score was associated with
      the RRR for pneumonia so that for each quality-point added, the RRR decreased by
      5.8% (95% confidence interval, 2.4%-9.3%). No association between trial quality
      and the impact of SDD was found on mortality. Of the individual trial quality
      characteristics, patient selection, allocation of intervention, and blinding most
      strongly influenced the treatment effect. CONCLUSIONS: The inverse relationship
      between methodological quality score and the benefit of SDD on the incidence of
      pneumonia may have resulted in overly optimistic estimates of SDD in prior meta
      analyses. This emphasizes the importance of rigorous trial design in evaluating
      preventive interventions in the intensive care unit.

PMID- 11466101
TI  - The rational clinical examination. Does this patient have clubbing?
AB  - CONTEXT: The association between digital clubbing and a host of diseases has been
      recognized since the time of Hippocrates. Although the features of advanced
      clubbing are familiar to most clinicians, the presence of early clubbing is often
      a source of debate. OBJECTIVE: To perform a systematic review of the literature
      for information on the precision and accuracy of clinical examination for
      clubbing. DATA SOURCES: The MEDLINE database from January 1966 to April 1999 was
      searched for English-language articles related to clubbing. Bibliographies of all
      retrieved articles and of standard textbooks of physical diagnosis were also
      searched. STUDY SELECTION: Studies selected for data extraction were those in
      which quantitative or qualitative assessment for clubbing was described in a
      series of patients. Sixteen studies met these criteria and were included in the
      final analysis. DATA EXTRACTION: Data were extracted by both authors, who
      independently reviewed and appraised the quality of each article. Data extracted
      included quantitative indices for distinguishing clubbed from normal digits,
      precision of clinical examination for clubbing, and accuracy of clubbing as a
      marker of selected diseases. DATA SYNTHESIS: The profile angle, hyponychial
      angle, and phalangeal depth ratio can be used as quantitative indices to assist
      in identifying clubbing. In individuals without clubbing, values for these
      indices do not exceed 176 degrees, 192 degrees, and 1.0, respectively. When
      clinicians make a global assessment of clubbing at the bedside, interobserver
      agreement is variable, with kappa values ranging between 0.39 and 0.90. Because
      of the lack of an objective diagnostic criterion standard, accuracy of physical
      examination for clubbing is difficult to determine. The accuracy of clubbing as a
      marker of specific underlying disease has been determined for lung cancer
      (likelihood ratio, 3.9 with phalangeal depth ratio in excess of 1.0) and for
      inflammatory bowel disease (likelihood ratio, 2.8 and 3.7 for active Crohn
      disease and ulcerative colitis, respectively, if clubbing is present).
      CONCLUSIONS: We recommend use of the profile angle and phalangeal depth ratio as
      quantitative indices in identifying clubbing. Clinical judgment must be exercised
      in determining the extent of further evaluation for underlying disease when these
      values exceed 180 degrees and 1.0, respectively.

PMID- 11466102
TI  - The pulmonary artery catheter-friend, foe, or accomplice?

PMID- 11466111
TI  - Asthma: prevalence, pathogenesis, and prospects for novel therapies.

PMID- 11466112
TI  - UN conference endorses battle plan for HIV/AIDS.

PMID- 11466113
TI  - Prostate disease begs understanding.

PMID- 11466114
TI  - FDA wants more restrictions on donated blood.

PMID- 11466119
TI  - Estimating hospital deaths due to medical errors: preventability is in the eye of
      the reviewer.
AB  - CONTEXT: Studies using physician implicit review have suggested that the number
      of deaths due to medical errors in US hospitals is extremely high. However, some
      have questioned the validity of these estimates. OBJECTIVE: To examine the
      reliability of reviewer ratings of medical error and the implications of a death
      described as "preventable by better care" in terms of the probability of
      immediate and short-term survival if care had been optimal. DESIGN: Retrospective
      implicit review of medical records from 1995-1996. SETTING AND PARTICIPANTS:
      Fourteen board-certified, trained internists used a previously tested structured
      implicit review instrument to conduct 383 reviews of 111 hospital deaths at 7
      Department of Veterans Affairs medical centers, oversampling for markers
      previously found to be associated with high rates of preventable deaths. Patients
      considered terminally ill who received comfort care only were excluded. MAIN
      OUTCOME MEASURES: Reviewer estimates of whether deaths could have been prevented
      by optimal care (rated on a 5-point scale) and of the probability that patients
      would have lived to discharge or for 3 months or more if care had been optimal
      (rated from 0%-100%). RESULTS: Similar to previous studies, almost a quarter
      (22.7%) of active-care patient deaths were rated as at least possibly preventable
      by optimal care, with 6.0% rated as probably or definitely preventable.
      Interrater reliability for these ratings was also similar to previous studies
      (0.34 for 2 reviewers). The reviewers' estimates of the percentage of patients
      who would have left the hospital alive had optimal care been provided was 6.0%
      (95% confidence interval [CI], 3.4%-8.6%). However, after considering 3-month
      prognosis and adjusting for the variability and skewness of reviewers' ratings,
      clinicians estimated that only 0.5% (95% CI, 0.3%-0.7%) of patients who died
      would have lived 3 months or more in good cognitive health if care had been
      optimal, representing roughly 1 patient per 10 000 admissions to the study
      hospitals. CONCLUSIONS: Medical errors are a major concern regardless of
      patients' life expectancies, but our study suggests that previous interpretations
      of medical error statistics are probably misleading. Our data place the estimates
      of preventable deaths in context, pointing out the limitations of this means of
      identifying medical errors and assessing their potential implications for patient
      outcomes.

PMID- 11466120
TI  - Albuminuria and risk of cardiovascular events, death, and heart failure in
      diabetic and nondiabetic individuals.
AB  - CONTEXT: Microalbuminuria is a risk factor for cardiovascular (CV) events. The
      relationship between the degree of albuminuria and CV risk is unclear.
      OBJECTIVES: To estimate the risk of CV events in high-risk individuals with
      diabetes mellitus (DM) and without DM who have microalbuminuria and to determine
      whether levels of albuminuria below the microalbuminuria threshold increase CV
      risk. DESIGN: The Heart Outcomes Prevention Evaluation study, a cohort study
      conducted between 1994 and 1999 with a median 4.5 years of follow-up. SETTING:
      Community and academic practices in North and South America and Europe.
      PARTICIPANTS: Individuals aged 55 years or more with a history of CV disease (n =
      5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine
      albumin/creatinine ratio (ACR) measurement. MAIN OUTCOME MEASURES: Cardiovascular
      events (myocardial infarction, stroke, or CV death); all-cause death; and
      hospitalization for congestive heart failure. RESULTS: Microalbuminuria was
      detected in 1140 (32.6%) of those with DM and 823 (14.8%) of those without DM at
      baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV
      events (RR, 1.83; 95% confidence interval [CI], 1.64-2.05), all-cause death (RR,
      2.09; 95% CI, 1.84-2.38), and hospitalization for congestive heart failure (RR,
      3.23; 95% CI, 2.54-4.10). Similar RRs were seen for participants with or without
      DM, even after adjusting for other CV risk factors (eg, the adjusted RR of the
      primary aggregate end point was 1.97 [95% CI, 1.68-2.31] in those with DM and
      1.61 [95% CI, 1.36-1.90] in those without DM). Compared with the lowest quartile
      of ACR (<0.22 mg/mmol), the RRs of the primary aggregate end point in the second
      quartile (ie, ACR range, 0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third
      quartile, 1.38 (95% CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth
      quartile, 1.97 (95% CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend <.001,
      even after excluding those with microalbuminuria). For every 0.4-mg/mmol increase
      in ACR level, the adjusted hazard of major CV events increased by 5.9% (95% CI,
      4.9%-7.0%). CONCLUSIONS: Our results indicate that any degree of albuminuria is a
      risk factor for CV events in individuals with or without DM; the risk increases
      with the ACR, starting well below the microalbuminuria cutoff. Screening for
      albuminuria identifies people at high risk for CV events.

PMID- 11466121
TI  - Neural mechanisms of anhedonia in schizophrenia: a PET study of response to
      unpleasant and pleasant odors.
AB  - CONTEXT: Loss of the capacity to experience pleasure (anhedonia) is a core
      clinical feature of schizophrenia. Although functional imaging techniques have
      been successful in identifying the neural basis of cognitive impairments in
      schizophrenia, no attempts to date have been made to investigate neural systems
      underlying emotional disturbances. OBJECTIVE: To study the neural basis of
      emotional processing in schizophrenia by exploring the pattern of brain responses
      to olfactory stimuli in patients and healthy volunteers. DESIGN: Positron
      emission tomographic study of patients with schizophrenia and healthy volunteers.
      Positron emission tomographic data were collected between July 21, 1995, and
      September 11, 1997, and data analyses were conducted in 1999-2001. SETTING: The
      Mental Health Clinical Research Center at the University of Iowa, Iowa City.
      PARTICIPANTS: Sixteen healthy volunteers with a mean age of 29.5 years and 18
      patients with schizophrenia and a mean age of 30.0 years. MAIN OUTCOME MEASURE:
      Areas of relative increase or decrease in regional cerebral blood flow, measured
      using positron emission tomography and the [(15)O]water method while participants
      performed an emotion-induction olfactory task to determine response to pleasant
      (vanillin) and unpleasant (4-methylvaleric acid) odors, compared between patients
      and healthy volunteers. RESULTS: Patients with schizophrenia subjectively
      experienced unpleasant odors in a manner similar to healthy volunteers but showed
      impairment in the experience of pleasant odors. The analysis of the regional
      cerebral blood flow revealed that patients failed to activate limbic/paralimbic
      regions (eg, insular cortex, nucleus accumbens, and parahippocampal gyrus) during
      the experience of unpleasant odors, recruiting a compensatory set of frontal
      cortical regions instead. CONCLUSION: Abnormalities in the complex functional
      interactions between mesolimbic and frontal regions may underlie emotional
      disturbances in schizophrenia.

PMID- 11466122
TI  - Acute effects of passive smoking on the coronary circulation in healthy young
      adults.
AB  - CONTEXT: Recent studies have shown that passive smoking is a risk factor for
      ischemic heart disease and may be associated with vascular endothelial
      dysfunction. The acute effects of passive smoking on coronary circulation in
      nonsmokers are not known. OBJECTIVE: To determine the acute effects of passive
      smoking on coronary circulation using coronary flow velocity reserve (CFVR),
      assessed by noninvasive transthoracic Doppler echocardiography. DESIGN, SETTING,
      AND PARTICIPANTS: Cross-sectional study conducted from September 2000 to November
      2000 among 30 Japanese men (mean age, 27 years; 15 healthy nonsmokers and 15
      asymptomatic active smokers) without history of hypertension, diabetes mellitus,
      or hyperlipidemia. MAIN OUTCOME MEASURES: Coronary flow velocity reserve,
      calculated as the ratio of hyperemic to basal coronary flow velocity induced by
      intravenous infusion of adenosine triphosphate and measured in each participant
      before and after a 30-minute exposure to environmental tobacco smoke. RESULTS:
      Heart rate and blood pressure responses to adenosine triphosphate infusion were
      not affected by passive smoking exposure in either group. Passive smoking
      exposure had no effect on basal coronary flow velocity in either group. Mean (SD)
      CFVR in nonsmokers was significantly higher than that in active smokers before
      passive smoking exposure (4.4 [0.91] vs 3.6 [0.88], respectively; P =.02), while
      CFVR after passive smoking exposure did not differ between groups (P =.83).
      Passive smoking exposure significantly reduced mean (SD) CFVR in nonsmokers (4.4
      [0.91] vs 3.4 [0.73], respectively; P<.001). CONCLUSIONS: Passive smoking
      substantially reduced CFVR in healthy nonsmokers. This finding provides direct
      evidence that passive smoking may cause endothelial dysfunction of the coronary
      circulation in nonsmokers.

PMID- 11466123
TI  - Bolus fibrinolytic therapy in acute myocardial infarction.
AB  - CONTEXT: New bolus fibrinolytics derived from the human tissue-type plasminogen
      activator (tPA) have emerged as a means of dissolution of occlusive thrombosis
      associated with acute myocardial infarction. OBJECTIVE: To review the new bolus
      fibrinolytic drugs derived from tPA: reteplase, lanoteplase, and tenecteplase.
      DATA SOURCES: The MEDLINE, EMBASE, and Current Contents databases were searched
      for articles from 1983 to 2001, using the index terms pharmacokinetics,
      pharmacodynamics, plasminogen activator, reteplase, lanoteplase, and
      tenecteplase. Additional data sources included bibliographies of articles
      identified on MEDLINE, EMBASE, and Current Content, inquiry of experts and
      pharmaceutical companies, and preliminary data presented at recent national and
      international cardiology conferences. STUDY SELECTION: We selected for review
      studies that evaluated the pharmacokinetics and pharmacodynamics of reteplase,
      lanoteplase, and tenecteplase, and assessed the effects of these bolus
      fibrinolytic drugs on the angiographic and immediate and long-term outcomes of
      patients. Of 138 articles identified, 38 were analyzed. DATA EXTRACTION: Data
      quality was determined by publication in the peer-reviewed literature or
      presentation at an official cardiology society-sponsored meeting. DATA SYNTHESIS:
      Tenecteplase and reteplase are comparable with accelerated infusion recombinant
      tPA in terms of efficacy and safety but more convenient because they are
      administered by bolus injection. Lanoteplase and heparin bolus plus infusion is
      as effective as tPA with regard to mortality, but the rate of intracranial
      hemorrhage is significantly higher. CONCLUSION: Given the ease of administration
      and the similar outcomes compared with accelerated infusion recombinant tPA, it
      is likely that a key component of contemporary reperfusion will include a bolus
      fibrinolytic.

PMID- 11466124
TI  - A 28-year-old woman with panic disorder.

PMID- 11466125
TI  - A 47-year-old woman with severe asthma, 1 year later.

PMID- 11466126
TI  - The AIDS research model: implications for other infectious diseases of global
      health importance.

PMID- 11466127
TI  - Even a little secondhand smoke is dangerous.

PMID- 11466133
TI  - Incomplete gastric metaplasia in children with insulin-dependent diabetes
      mellitus and celiac disease. An ultrastructural study.
AB  - BACKGROUND: The association of insulin-dependent diabetes mellitus (IDDM) and
      celiac disease (CD) has been widely reported in children but the relationship
      between the two conditions is incompletely understood. Moreover, specific studies
      on intestinal biopsies of patients with the association of the two diseases are
      still lacking. METHODS: We studied the ultrastructure of the duodenal mucosa in
      12 patients with both IDDM and CD. RESULTS: All patients had either total or
      partial atrophy of duodenal mucosa. In seven subjects, an accumulation of
      electrondense granules in the apical cytoplasm of groups of enterocytes was
      found. In four of them, a double population of granules existed (mean diameter:
      400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other
      three patients, only smaller granules (100- 200 nm) were found in the
      enterocytes. CONCLUSIONS: The present work suggests that patients with IDDM/CD
      may represent a subgroup in the context of the CD population. Intestinal biopsies
      of such individuals often show accumulation of electrondense granules in the
      apical cytoplasm of enterocytes that can be interpreted as incomplete gastric
      metaplasia.

PMID- 11466134
TI  - The electrocardiogram: from Einthoven to molecular genetics.

PMID- 11466135
TI  - Qt dispersion and mortality in the elderly.
AB  - BACKGROUND: The prognostic value of QT interval dispersion measured from a
      standard 12-lead electrocardiogram (ECG) in the general population is not well
      established. The purpose of the present study was primarily to assess the value
      of QT interval dispersion obtained from 12-lead ECG in the prediction of total,
      cardiac, stroke, and cancer mortality in the elderly. METHODS: A random
      population sample of community-living elderly people (n = 330, age > or = 65
      years, mean 74 +/- 6 years) underwent a comprehensive clinical evaluation,
      laboratory tests, and 12-lead ECG recordings. RESULTS: By the end of the 10-year
      follow-up, 180 subjects (55%) had died and 150 (45%) were still alive. Heart rate
      corrected QT (QTc) dispersion had been longer in those who had died than in the
      survivors (75 +/- 32 ms vs 63 +/- 35 ms, P = 0.01). After adjustment for age and
      sex in the Cox proportional hazards model, prolonged QTc dispersion (> or = 70
      msec) predicted all-cause mortality (relative risk [RR] 1.38, 95% confidence
      interval [CI] 1.02-1.86) and particularly stroke mortality (RR 2.7, 95% CI 1.29
      5.73), but not cardiac (RR 1.38, 95% CI 0.87-2.18) or cancer (RR 1.51, 95% CI
      0.91-2.50) mortality. After adjustment for age, sex, body mass index, blood
      pressure, blood glucose and cholesterol concentrations, functional class, history
      of cerebrovascular disease, diabetes, smoking, previous myocardial infarction,
      angina pectoris, congestive heart failure, medication, left ventricular
      hypertrophy on ECG, presence of atrial fibrillation and R-R interval, increased
      QTc dispersion still predicted stroke mortality (RR 3.21, 95% CI 1.09-9.47), but
      not total mortality or mortality from other causes. The combination of increased
      QTc dispersion and left ventricular hypertrophy on ECG was a powerful independent
      predictor of stroke mortality in the present elderly population (RR 16.52, 95% CI
      3.37-80.89). QTcmin (the shortest QTc interval among the 12 leads of ECG)
      independently predicted total mortality (RR 1.0082, 95% CI 1.0028-1.0136, P =
      0.003), cardiac mortality (RR 1.0191, 95% CI 1.0102-1.0281, P < 0.0001) and
      cancer mortality (RR 1.0162, 95% CI 1.0049-1.0277, P = 0.005). CONCLUSIONS:
      Increased QTc dispersion yields independent information on the risk of dying from
      stroke among the elderly and its component, QTcmin, from the other causes of
      death.

PMID- 11466136
TI  - Hormone replacement therapy shortens QT dispersion in healthy postmenopausal
      women.
AB  - BACKGROUND: The aim of the study was to investigate the effects of hormone
      replacement therapy (HRT) on myocardial repolarization characteristics in
      postmenopausal women without coronary artery disease. METHODS: Fifty-one
      consecutive healthy postmenopausal women (age 48 +/- 5) with negative exercise
      stress testing were prospectively enrolled into the study. Standard 12-lead
      electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT
      intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and
      corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated
      equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625
      mg/day CEE alone depending on the hysterectomy status. RESULTS: Although not
      statistically significant, CEE alone or in combination with MPA increased QTmax
      and QTmin values. However, the increase in QTmin was greater than the increase in
      QTmax, which resulted in statistically significant shortening of QTd (P = 0.007
      in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation
      of QTcmin values after 6 months in patients assigned to the CEE group (P =
      0.001). The QTcd values were significantly shortened by HRT with both regimens
      (for CEE group 49 +/- 13 ms vs 38 +/- 13 ms, P = 0.01; for CEE + MPA group 49 +/-
      14 ms vs 36 +/- 13, P < 0.001). CONCLUSION: HRT significantly decreased the QTd
      and QTcd in postmenopausal women without coronary artery disease, independent of
      the addition of MPA to the regimen. This improvement in myocardial repolarization
      may be one of the mechanisms of the favorable effects of HRT on cardiovascular
      system. However, the clinical implications of the shortening of QTd in
      postmenopausal women with HRT must be clarified.

PMID- 11466137
TI  - ST variability during the first 4 hours of acute myocardial infarction predicts 1
      year mortality.
AB  - BACKGROUND: Early and complete myocardial reperfusion is the goal when treating a
      patient with acute myocardial infarction. To achieve this in each individual, an
      on-line, accurate, easily handled and preferably noninvasive technique to monitor
      flow alterations is needed. Recurrent ST-segment elevation has been shown to
      reflect cyclic disturbances in perfusion. METHODS: We have retrospectively
      analyzed ST variability in 102 patients with acute myocardial infarction
      randomized to 100 mg of rt-Pa or placebo. Patients were monitored for 24 hours
      using vectorcardiography. RESULTS: Patients alive at one year (86%) had
      significantly less ST variability during the first four hours: 4.3 versus 7.1
      episodes, P = 0.007. Patients having six or more ST episodes showed a 31.3% one
      year mortality as compared to no mortality in patients having no ST variability.
      Furthermore ST variability was reduced by fibrinolysis. CONCLUSION: Early ST
      variability detectable in real time is associated with worse outcome.

PMID- 11466138
TI  - Predicting the recurrence of ventricular tachyarrhythmias from T-wave alternans
      assessed on antiarrhythmic pharmacotherapy: a prospective study in patients with
      dilated cardiomyopathy.
AB  - BACKGROUND: Microvolt T-wave alternans (TWA) has been proposed as a useful index
      to identify patients at risk of ventricular tachyarrhythmias. Recent studies have
      demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide,
      decrease the prevalence of TWA. In this study, we tested whether TWA in patients
      on antiarrhythmic pharmacotherapy significantly predicts the recurrence of
      ventricular tachyarrhythmias in patients with dilated cardiomyopathy. METHODS: To
      evaluate the ability to predict the recurrence of ventricular tachyarrhythmias,
      determinate TWA and left ventricular ejection fraction (LVEF) were prospectively
      assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on
      antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or
      ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17
      patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study
      endpoint was the first recurrence of sustained VT or VF on treatment during the
      follow-up period. RESULTS: TWA was positive on antiarrhythmic pharmacotherapy in
      30 patients (61%). During a follow-up of 13 +/- 11 months, the sustained VT or VF
      recurred in 21 of the 41 patients (51%) with available follow-up data. The
      sensitivity of TWA and LVEF for predicting recurrence of ventricular
      tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive
      value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan-Meier
      event-free analysis revealed that TWA was a significant risk stratifier (P =
      0.02), whereas LVEF was not. CONCLUSIONS: This prospective study suggests that
      TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even
      on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA
      may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs
      for ventricular tachyarrhythmias.

PMID- 11466139
TI  - Is QT dispersion associated with sudden cardiac death in patients with
      hypertrophic cardiomyopathy?
AB  - QT dispersion is significantly greater in patients with hypertrophic
      cardiomyopathy (HCM) than that in healthy subjects. Few data exist regarding the
      prognostic value of QT dispersion in HCM. In this study, we retrospectively
      investigated the association between QT dispersion and sudden cardiac death in 46
      patients with HCM (mean 33.1 +/- 15.5 years, 32 men). The case group consisted of
      23 HCM patients who died suddenly, and the control group consisted of 23 HCM
      patients who survived uneventfully during follow-up. Study patients were pair
      matched for age, gender, and maximum left ventricular wall thickness. QT
      dispersion (maximum minus minimum QT interval) was manually measured on early 12
      lead ECGs using a digitizing board. An in-house program was used for calculating
      QT interval, QT dispersion, JT interval, and JT dispersion (maximum minus minimum
      J point to T end interval). Patients in the case group tended to have shorter RR
      intervals than those in the control group (777 +/- 171 vs 856 +/- 192 ms, P =
      0.08). Maximum corrected QT and JT intervals did not discriminate the case group
      from controls (489 +/- 29 vs 479 +/- 27 ms, P = NS; 375 +/- 36 vs 366 +/- 22 ms,
      P = NS, respectively). Greater QT dispersion and JT dispersion were found in the
      case group compared with controls (74 +/- 28 vs 59 +/- 21 ms, P = 0.02 and 76 +/-
      32 vs 59 +/- 26 ms, P = 0.03, respectively). The measurements of maximum QT, JT,
      and T peak to T end intervals, precordial QT and JT dispersion, and T peak and T
      end dispersion were all comparable between the two groups (P = NS for all). No
      systematic changes in ECG measurements were found from late ECGs of the case
      group compared to those from early ECGs (P = NS). No correlation between maximum
      left ventricular wall thickness and QT dispersion, JT dispersion, maximum QTc or
      JTc intervals was observed (r < 0.29, P > 0.05 for all). Our results show that
      increased QT dispersion and JT dispersion is weakly associated with sudden
      cardiac death in the selected patients with HCM.

PMID- 11466140
TI  - Perception and documentation of arrhythmias after successful radiofrequency
      catheter ablation of accessory pathways.
AB  - BACKGROUND: Some patients continue to have palpitations in spite of successful
      ablation of Wolff-Parkinson-White (WPW) syndrome. Recurrence of accessory
      pathways as well as unrelated arrhythmias may explain the symptoms. METHODS: We
      followed 194 consecutive patients after successful radiofrequency catheter
      ablation of overt (147) or concealed (47) WPW syndrome. The mean duration of
      symptoms was 16 +/- 13 years. Atrial fibrillation was documented in 54 patients
      (24%) prior to ablation. 185 patients responded to a questionnaire 24 +/- 12
      months after ablation. RESULTS: The physical well-being was improved in 94%,
      unchanged in 5%, and deteriorated in 1%. However, 76 patients (39%) reported
      arrhythmia symptoms, in 40 patients causing pharmacological treatment (14
      patients) and/or continued contact with their doctor. The underlying arrhythmias
      were orthodromic tachycardia (10), atrial fibrillation (12), premature beats
      (12), atrial flutter (1), and ventricular tachycardia (1), while in four patients
      no explanation was found. Minor symptoms in the other 36 patients were explained
      by premature beats in 29, while unexplained in 7. All patients with atrial
      fibrillation after ablation had atrial fibrillation before ablation. Ten relapses
      of WPW syndrome occurred: eight were known before the time of the questionnaire,
      two were confirmed at transesophageal atrial stimulation. CONCLUSION: 94%
      patients with a long history of tachyarrhythmias due to the WPW syndrome reported
      improved physical well-being after ablation, but palpitations were common during
      a 2-year follow-up period; 8% continued to use pharmacological antiarrhythmic
      treatment. Five percent had symptomatic relapses and in 6% atrial fibrillation
      episodes reoccurred, i.e., in half of those who had atrial fibrillation before
      ablation.

PMID- 11466141
TI  - The normal sequence of right and left atrial contraction.
AB  - OBJECTIVE: To study the sequence of atrial activation and the interatrial
      electromechanical delay (IEmD) noninvasively in healthy subjects during sinus
      rhythm (SR). METHODS AND RESULTS: In 66 SR healthy subjects P-wave activation was
      analyzed by means of vectorcardiography. The timing of atrial contractions was
      measured as the intervals between the P-wave and the A-wave of the Doppler right
      and left ventricular inflows (P-A(t) and P-A(m)), and IEmD was calculated as the
      algebraic difference P-A(m)- P-A(t). In the horizontal plane the
      vectorcardiographic P-loop was anteroposterior ("typical", 41 subjects), anterior
      (18), or posterior (7). IEmD (mean +/- SE 17 +/- 8 ms) was directly related to R
      R and P-R intervals. IEmD was significantly shorter in anterior and posterior P
      loops than in the typical (6.5 +/- 5.3 and 8.1 +/- 10.1, respectively, vs 24.2 +/
      3.1 ms). In the posterior P-loop group, who exhibited longer P-A(t), mitral E
      wave velocity and E/A ratio were reduced, and left atrial booster function was
      increased. CONCLUSION: IEmD was widely variable in SR, reflecting the origin site
      of sinus impulse, which independently influenced ventricular filling dynamics.

PMID- 11466142
TI  - The diagnostic value of 12-lead electrocardiogram in predicting infarct-related
      artery and right ventricular involvement in acute inferior myocardial infarction.
AB  - BACKGROUND: The aim of the present study was to investigate the predictive value
      of presentation and 24-hour electrocardiograms in defining the infarct-related
      artery (IRA), its lesion segment, and the right ventricular involvement in acute
      inferior myocardial infarction (MI). METHODS: One hundred forty-nine patients
      with acute inferior MI were included. Infarct-related artery, its lesion segment,
      and the validity of new ECG criteria for the diagnosis of right ventricular MI
      (RVMI) were investigated by means of criteria obtained from admission and 24-
      hour ECGs. RESULTS: The presence of ST-segment elevation in lead III > lead II
      criterion (Criterion 1) and ST-segment depression in lead I > lead aVL criterion
      (Criterion 2) from admission ECG defined the right coronary artery (RCA) as IRA
      with a sensitivity of 64% and a specificity of 100%. These two criteria also
      defined the proximal or mid lesions in RCA as culprit lesions (sensitivity of
      99%, specificity of 96%). Absence of these two criteria indicated Cx as IRA with
      a sensitivity of 50% and a specificity of 97%. The depth of Q wave in lead III >
      lead II criterion (Criterion 3) had no value for discrimination of IRA, but the
      width of Q wave in lead III > lead II criterion (Criterion 4) supported the RCA
      to be IRA with a sensitivity of 60% and a specificity of 61% (Criteria 3 and 4
      were obtained from 24-hour ECGs). The finding of Criterion 1 plus Criterion 5 (ST
      elevation in V(1) but no ST elevation in V2) on admission ECG had a sensitivity
      of 63% and a specificity of 99% in the diagnosis of RVMI. CONCLUSION: We
      concluded that 12-lead ECG is a cheap, easy, and readily obtainable diagnostic
      approach in discrimination of IRA and its culprit lesion segment. However,
      despite high specificity, due to moderate degree sensitivity, its value for the
      diagnosis of RVMI is questionable.

PMID- 11466143
TI  - Value and limitations of ambulatory ECG monitoring for assessment of myocardial
      ischemia.
AB  - Ambulatory ECG monitoring (AEM) is the only available method to assess the
      presence and severity of myocardial ischemia during daily life. Several
      investigators have shown that the recording systems currently used can detect
      ischemic changes with similar accuracy as treadmill exercise testing. Ischemic
      changes on AEM are, however, present in only 40%-60% of patients with coronary
      artery disease (CAD) and positive exercise tests. For this reason, and because of
      the high day-to-day variability in daily ischemic changes, AEM cannot be used as
      a screening tool for detecting CAD or for evaluating severity of ischemia in
      individual patients. In patients with proven CAD, ischemic changes on AEM are
      associated with an adverse outcome in patients with stable and unstable ischemic
      syndromes, and in postmyocardial infarction patients. Suppression of daily
      ischemia seems to be associated with improved outcome. The mechanism of daily
      ischemia is not identical to exercise-induced ischemia. In addition to increased
      demand, which is a major contributor to AEM detected-ischemia, increased coronary
      tone also seems to play a major role. AEM has been shown to be a useful and
      reliable tool to assess the efficacy of various antiischemic drugs.

PMID- 11466144
TI  - The history of bundle branch block. Introductory note.

PMID- 11466145
TI  - Familial Mahaim syndrome.
AB  - We describe the occurrence of Mahaim syndrome in a mother and her son. The
      occurrence of such a rare disorder in two members of a family is noteworthy, has
      not been reported before, and suggests the possibility of genetic transmission. A
      genetic transmission of supraventricular tachycardia has been described only in
      rare cases for the Wolff-Parkinson-White syndrome. No such data is available for
      the Mahaim syndrome.

PMID- 11466146
TI  - Shu 508 A (Levovist)-enhanced Doppler echocardiography improves the assessment of
      valvular heart disease.
AB  - OBJECTIVE: To investigate whether intravenous injection of SHU 508 A improves the
      diagnostic accuracy of Doppler echocardiography in the assessment of valvular
      pathologies. METHODS AND RESULTS: One hundred and twenty-five consecutive
      patients with valvular pathology (aortic stenosis, n = 48; aortic regurgitation,
      n = 20; mitral stenosis, n = 21; and mitral regurgitation, n = 36) and
      diagnostically insufficient Doppler signal were enrolled in this multicenter
      study. The severity of valvular pathology was graded on a four-point scale using
      unenhanced and contrast-enhanced Doppler echocardiography as well as cardiac
      catheterization. Agreement with cardiac catheterization findings increased from
      63% using the unenhanced examination to 73% using the contrast-enhanced Doppler
      examination. Grading was possible in all patients using SHU 508 A, whereas the
      unenhanced Doppler examination remained inconclusive in six patients. The
      weighted kappa coefficient between contrast-enhanced Doppler and cardiac
      catheterization for all diagnoses was 0.76 as compared to 0.68 between unenhanced
      Doppler and cardiac catheterization. Agreement was especially improved in aortic
      stenosis (kappa 0.69 unenhanced vs 0.81 contrast-enhanced) and in aortic
      regurgitation (kappa 0.45 unenhanced vs 0.75 contrast-enhanced). Patients with
      mitral stenosis and mitral regurgitation experienced less improvement.
      CONCLUSIONS: In case of an inconclusive unenhanced Doppler echo study, the
      administration of a left heart contrast agent should be considered. SHU 508 A is
      especially useful in improving the severity grading of aortic stenosis and aortic
      regurgitation, while grading of mitral stenosis and mitral regurgitation is less
      improved.

PMID- 11466147
TI  - Dobutamine stress echocardiography response of asymptomatic patients with
      diabetes.
AB  - AIMS: This study investigated the role of dobutamine stress echocardiography for
      the silent diagnosis of myocardial ischemia in a diabetic population. Results
      from the stress test were compared between diabetic and nondiabetic groups.
      METHODS: Forty-nine diabetics and 63 consecutive nondiabetics underwent
      dobutamine stress echocardiography between April and December 1999, to check for
      new regional wall-motion abnormalities. A single operator, using the same
      echograph with tissue harmonic imaging in each case, performed all the
      examinations, using the same techniques. RESULTS: Significant coronary artery
      disease was detected in 9% of asymptomatic diabetics. Dynamic left ventricular
      obstruction was observed in 59% of the diabetic population and only 22% in the
      nondiabetic population. One patient suffered an adverse event (fast atrial
      fibrillation) during the stress test. Cardiac frequency at the beginning and end
      of the stress test differed significantly between the two populations.
      CONCLUSION: Dobutamine stress echocardiography allows for detection of silent
      myocardial ischemia. In the diabetic population, we describe, for the first time
      under dobutamine infusion, a great number of dynamic left ventricular
      obstructions.

PMID- 11466148
TI  - Flail aortic valve and acute aortic regurgitation due to spontaneous localized
      intimal tear of ascending aorta.
AB  - This report describes the transesophageal echocardiographic findings of acute
      severe aortic regurgitation resulting from localized transverse intimal tear of
      ascending thoracic aorta which could not be suspected as a cause of flail aortic
      valve preoperatively. In patients with chest pain and acute aortic regurgitation
      associated with flail aortic valve, localized intimal tear of aorta should be
      considered as a possible cause of flail aortic valve.

PMID- 11466149
TI  - Aortic transsection after blunt chest trauma.
AB  - We report a case of an 18-year-old female who developed an extensive hemothorax
      after blunt chest trauma. Transesophageal echocardiography (TEE) showed
      transsection of the aorta at the level of the isthmus and turbulent flows in
      several places around the aorta. We discuss the contribution of TEE for detecting
      traumatic injuries to the thoracic aorta.

PMID- 11466150
TI  - Left atrial appendage thrombus as a source of peripheral embolism: TEE evidence
      of direct relationship.

PMID- 11466151
TI  - Prolapsing aortic dissection.

PMID- 11466152
TI  - Transesophageal color Doppler three-dimensional echocardiographic detection of
      prosthetic aortic valve dehiscence: correlation with surgical findings.
AB  - Three-dimensional echocardiography is being used with increasing frequency to
      evaluate cardiac function and structure. We present two cases of prosthetic
      aortic valve endocarditis where three-dimensional transesophageal
      echocardiography correlated with the intraoperative surgical findings of
      prosthetic dehiscence and communication with an abscess cavity. When compared
      with two-dimensional transesophageal echocardiography, three-dimensional
      echocardiography was more accurate in defining the exact site of dehiscence and
      communication with an abscess cavity. The echocardiographic images were oriented
      as a clockface watch to conform to the surgeon's visualization of the aortic root
      as viewed from the right side of the patient.

PMID- 11466154
TI  - Systemic venous abnormalities: embryologic and echocardiographic considerations.
AB  - The echocardiographic diagnosis of systemic venous anomalies often is rendered
      difficult by the variety of lesions that exist. An understanding of the
      embryologic processes that result in these lesions is essential for accurate
      identification, since these lesions often are not obvious on routine
      echocardiographic examination. Standard echocardiographic views may demonstrate
      some lesions, whereas many require modified views to outline the abnormal
      systemic venous anatomy. This paper reviews the basic embryologic processes of
      the development of the normal and abnormal systemic venous system, as well as the
      echocardiographic identification of these major systemic venous malformations.

PMID- 11466155
TI  - Cross-sectional echocardiographic assessment of atrioventricular septal defect:
      basic morphology and preoperative risk factors.
AB  - Accurate evaluation of an atrioventricular septal defect is readily achieved by
      echocardiography. A sound understanding of the basic morphology and associated
      lesions is key to this approach. This article first details the features that are
      common to all hearts with an atrioventricular septal defect, irrespective of the
      presence or absence of an interatrial or interventricular communication. These
      common features are: (1) inlet outlet disproportion; (2) absence of the
      atrioventricular muscular septum; (3) abnormal position of the left ventricular
      papillary muscles; (4) abnormal configuration of the atrioventricular valves and,
      (5) cleft in the left atrioventricular valve. These are all predicated by a
      sprung atrioventricular junction. Second, is a detailed outline of the associated
      risk factors that must be identified by the echocardiographer prior to presenting
      the patient for surgical management, with the most important ones being
      abnormalities of the left atrioventricular valve and left ventricular outflow
      tract obstruction. Indeed, in this current era it is rarely necessary to perform
      other investigations prior to surgical repair.

PMID- 11466156
TI  - Three-dimensional echocardiography of the atrial septum.
AB  - This article details the important contribution of three-dimensional
      echocardiography for catheterization device closure of secundum atrial septal
      defects. Aspects presented include three-dimensional echocardiographic
      application in preselection of patients and in selection of the type and size of
      the atrial septal occluder devices. Unique three-dimensional echocardiographic
      imaging planes are shown that depict the size and shape of the defect, the
      important rim tissue surrounding the defect, and the images that demonstrate
      successful device placement. Details of the acquisition phase, digital
      reformatting, and the eventual rendering of standard three-dimensional
      echocardiographic imaging planes of the atrial septum are shown. Three
      dimensional echocardiography not only provides important additional information,
      but also enhances understanding of standard two-dimensional studies.

PMID- 11466157
TI  - Echocardiography of serous effusions adjacent to the heart.
AB  - Sonolucent spaces in close proximity to the heart are common in routine clinical
      echocardiographic practice, yet apart from pericardial effusions have received
      little attention. These clear spaces can represent left or right pleural
      effusions, ascites, pericardial cysts, or unusual diaphragmatic hernias. All
      these entities have typical echocardiographic features, including location, size,
      shape, and anatomic relationships to contiguous structures. In addition,
      loculated pericardial effusions, with or without associated tamponade, have to be
      considered in the differential diagnosis. In this brief review, we discuss and
      illustrate these various types of juxtacardiac sonolucencies.

PMID- 11466158
TI  - Regional cerebral blood flow in cocaine- versus methamphetamine-dependent
      patients with a history of alcoholism.
AB  - Although abuse of cocaine or methamphetamine usually takes place in the context
      of heavy drinking, there is little information on the effects of such substance
      use comorbidity on brain perfusion. We explored similarities and differences in
      the effects of these two drugs in combination with alcohol on brain function
      using SPECT. Global and regional cerebral blood flow (CBF) were examined in 7
      abstinent cocaine-dependent alcoholics (CDA; mean age = 39.2 yr, S.D. = 9.2 yr),
      7 abstinent methamphetamine-dependent alcoholics (MDA; mean age = 36.8 yr, S.D. =
      5.0 yr), and 7 non-alcoholic/non-stimulant abusing controls (NAC; mean age = 37.3
      yr, S.D. = 9.6 yr). MDA had significantly lower global CBF than CDA who, in turn,
      were significantly lower than NAC. In addition, CDA had abnormal perfusion in the
      superior posterior frontal region compared to NAC; while MDA did not display
      specific regional deficits. Therefore, it appears that cocaine alters the
      relationship between global and regional CBF in alcoholics, while methamphetamine
      does not.

PMID- 11466159
TI  - Symptom reduction and suicide risk in patients treated with placebo in
      antidepressant clinical trials: a replication analysis of the Food and Drug
      Administration Database.
AB  - The assumption that depressed patients who are assigned to placebo in
      antidepressant clinical trials are exposed to substantial morbidity and mortality
      has not been based on research data. Because of worldwide concern about placebo
      use and the implications of our earlier findings of no increased suicide risk in
      placebo-treated patients, we conducted a replication study in a new patient
      sample. We assessed suicide risk and symptom reduction among placebo-treated
      patients participating in antidepressant clinical trials for two recently
      approved antidepressants, venlafaxine ER and citalopram, which were unavailable
      during our previous study. Among 23,201 participant patients, 32 committed
      suicide and 172 attempted suicide. Rates of suicide and attempted suicide did not
      differ significantly among the placebo- and drug-treated groups. Based on patient
      exposure years, annual rates of suicide and attempted suicide were 0.5 and 6.7%
      with placebo, 0.9% with active comparator (rates for attempted suicide are
      unavailable), and 0.6 and 6.3% with investigational antidepressants. Symptom
      reduction was 47.9% with investigational drugs (n = 1172), 47.5% with active
      comparators (n = 161), and 35.5% with placebo (n = 606). These data may inform
      discussions about the use of placebo in antidepressant clinical trials.

PMID- 11466160
TI  - Effect of fluoxetine on regional cerebral metabolism in autistic spectrum
      disorders: a pilot study.
AB  - The regional metabolic effects of fluoxetine were examined in patients with
      autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic
      Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1),
      entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients
      received (18)F-deoxyglucose positron emission tomography with co-registered
      magnetic resonance imaging at baseline and at the end of the period of fluoxetine
      administration. After treatment, the patients showed significant improvement on
      the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale
      and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores
      showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates
      were significantly higher in the right frontal lobe following fluoxetine,
      especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients
      with higher metabolic rates in the medial frontal region and anterior cingulate
      when unmedicated were more likely to respond favourably to fluoxetine. These
      results are consistent with those in depression indicating that higher cingulate
      gyrus metabolic rates at baseline predict SRI response.

PMID- 11466161
TI  - Treatment with controlled-release lovastatin decreases serum concentrations of
      human beta-amyloid (A beta) peptide.
AB  - The deposition of beta-amyloid (A beta) in neuronal plaques is believed to be
      crucial for the initiation and progression of Alzheimer's disease (AD). Studies
      in vitro have shown that inhibiting cholesterol metabolism with lovastatin, or
      its active metabolite lovastatin acid, lowers A beta production. To examine the
      effects of lovastatin on A beta in vivo, human subjects who had elevated low
      density lipoprotein cholesterol were treated during a double-blind, randomized,
      placebo-controlled study with 10, 20, 40 or 60 mg once-daily doses of a
      controlled-release formulation of lovastatin, or matching placebo. Serum A beta
      concentrations were measured before and after up to 3 months of treatment. Mean
      and median changes from baseline in serum A beta concentrations showed a dose
      dependent decrease, and analysis of variance indicated that treatment was
      statistically significant (p < 0.0348). Differences between the 40- and 60-mg
      dose groups and placebo were statistically significant (Dunnett's p < or = 0.05).

PMID- 11466162
TI  - Neuropsychological changes after 30-day Ginkgo biloba administration in healthy
      participants.
AB  - Ginkgo biloba extract (EGb) from the world's oldest living tree has been reputed
      to ameliorate cognitive decline in the elderly and slow cognitive deterioration
      in patients with dementia of the Alzheimer's type. EGb remains as one of the most
      popular plant extracts to alleviate symptoms associated with a range of cognitive
      disorders such as Alzheimer's disease, vascular dementia and age-related amnesic
      conditions. EGb is known to contain a range of chemically active components that
      have antagonistic effects on platelet-activating factor, free-radical scavenging
      activity and direct effects on the cholinergic neurotransmitter system. Recently
      there has been much speculation, that EGb may act as a 'smart drug' or nootropic
      agent in the healthy young to improve intelligence. We conducted a 30-d
      randomized, double-blind, placebo-controlled clinical trial in which 61
      participants were administered a battery of validated neuropsychological tests
      before and after treatment. Statistical analysis indicated significant
      improvements in speed of information processing working memory and executive
      processing attributable to the EGb.

PMID- 11466163
TI  - Effectiveness of clozapine and olanzapine: a comparison in severe, psychotically
      ill patients.

PMID- 11466164
TI  - Advances in paediatric neuropsychopharmacology: an overview.
AB  - This Special Section of Int J Neuropsychopharmacol highlights current progress in
      paediatric neuropsychopharmacology. Combining critical reviews and, in some
      cases, new data, specific topics include: biological findings in major
      depression, sleep dysregulation in depressed youth, cardiovascular and
      ventilatory dysregulation in panic disorder, paediatric autoimmune
      neuropsychiatric disorder associated with strep (PANDAS), age of onset as a
      subtype marker in tic and obsessive--compulsive disorders (OCD), functional and
      pharmaconeuroanatomy of OCD and the behavioural pharmacokinetics of
      methylphenidate. In this introductory section, these articles are placed in the
      context of the state-of-the field and, more specifically, within the framework of
      recent NIMH initiatives in paediatric neuropsychopharmacology.

PMID- 11466165
TI  - Biological studies in depressed children and adolescents.
AB  - The objective was to review the literature on the biological correlates of major
      depressive disorder (MDD) in children and adolescents. A computerized search for
      articles published during the last 20 years was done and selected studies
      presented. To date, examination of growth hormone (GH), prolactin, and cortisol
      levels after pharmacological stimulation have shown abnormalities in the
      secretion of these hormones (e.g. blunted GH secretion after the administration
      of growth hormone releasing hormone). Identical results have been found in never
      depressed children at high risk to develop MDD due to high family loading for MDD
      suggesting that alteration in certain hormonal systems may be trait markers for
      MDD. Other biological studies (e.g. the hypothalamic--pituitary axis, sleep
      electroencephalogram) have yielded more inconsistent results with subjects with
      melancholic symptoms, severe depressions, and older age showing some
      abnormalities similar to the ones reported in adults with MDD. Factors such age,
      sex, maturation, psychiatric family history and exposure to stress need to be
      considered since they also affect the same biological systems associated with the
      aetiology of MDD. Considerable biological research has been done in youth with
      MDD. Further research is needed to investigate whether these markers predict the
      development of new episodes of MDD, recurrences, and treatment response. Also,
      these and other studies using more sophisticated methods (e.g. functional MRI)
      aimed at elucidating the interrelationship between biological and other risk
      factors are needed.

PMID- 11466166
TI  - Sleep polysomnography as a predictor of recurrence in children and adolescents
      with major depressive disorder.
AB  - Adults with major depressive disorder (MDD) demonstrate certain sleep
      polysomnographic abnormalities, including sleep continuity disturbances, reduced
      slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM
      density. Findings of sleep EEG studies in depressed children and adolescents have
      yielded conflicting results, possibly because of methodological variations across
      the studies. Generally, however, studies have demonstrated that depressed
      children and adolescents exhibit less sleep continuity and non-REM sleep
      differences in comparison with control subjects than do adults. Thus, results
      from adult sleep polysomnography studies cannot necessarily be generalized to
      children and adolescents. Depressed adults who have reduced REM latency during
      the symptomatic episode appear more likely to have a relapse once treatment is
      discontinued than those with normal REM latency. No studies of the relationship
      between sleep polysomnographic variables and clinical course have been reported
      in depressed children and adolescents. Data for baseline clinical variables and 3
      nights of sleep polysomnography were examined in 113 depressed children (< or =
      12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57
      outpatients) where data was available on at least 1 yr of naturalistic follow-up.
      Subjects came from 2 studies of sleep polysomnography in children and adolescents
      with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval
      Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from
      the index episode of MDD and recurrence, a new episode of meeting full criteria
      for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had
      recovered from their index episode of depression (minimal or no symptoms for 60
      d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The
      majority of subjects (55%) who had a recurrence were not on medication at the
      time of recurrence. Subjects who had a recurrence were more likely to report
      suicidal thoughts or attempts at baseline compared to those without a recurrence
      (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects
      with a later recurrence had decreased sleep efficiency and delayed sleep onset
      (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39
      compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline
      suicidal ideation and sleep dysregulation on sleep polysomnography predicted
      recurrence in a large sample of depressed children and adolescents. Depression in
      children and adolescents is frequently a chronic, recurrent illness. Factors that
      can predict clinical course are important in increasing our understanding of
      depression in this age group.

PMID- 11466167
TI  - Disentangling chronological age from age of onset in children and adolescents
      with obsessive--compulsive disorder.
AB  - Although paediatric obsessive--compulsive disorder (OCD) is increasingly
      recognized as a putative developmental subtype of the disorder, it remains
      uncertain as to whether additional subtyping by age at onset in childhood or
      adolescence is warranted. Subjects included children and adolescents meeting DSM
      III-R and DSM-IV criteria for OCD referred to a specialized OCD clinic. All youth
      were systematically evaluated with structured diagnostic interviews and clinical
      assessment by an OCD expert. Irrespective of current age, an earlier age at onset
      predicted increased risk for attention deficit hyperactivity disorder, simple
      phobia, agoraphobia and multiple anxiety disorders. In contrast, mood and
      psychotic disorders were associated with chronological age and were more
      prevalent in older subjects. Tourette's disorder showed associations with both
      chronological age and age at onset. Chronological age and age at onset predicted
      different patterns of comorbidity and dysfunction in children and adolescents
      with OCD. Considering the heterogeneity of OCD, age at onset may help identify
      meaningful developmental subtypes of the disorder beyond chronological age.

PMID- 11466168
TI  - Brain anatomy and chemistry may predict treatment response in paediatric
      obsessive--compulsive disorder.
AB  - Obsessive--compulsive disorder (OCD) is a severe, highly prevalent and often
      chronically disabling illness with frequent onset in childhood and adolescence.
      This underscores the importance of studying the illness during childhood near the
      onset of illness to minimize potential confounds of long-term illness duration
      and treatment intervention as well as to examine the developmental underpinnings
      of the illness. In this review, the authors focus on an integrated series of
      brain-imaging studies in paediatric OCD suggesting a reversible glutamatergically
      mediated thalamo-cortical--striatal dysfunction in OCD and their relevance for
      improved diagnosis and treatment of the condition. Developmental neurobiological
      models for OCD are presented and particular attention is devoted to evaluating
      neuroimaging studies designed to test these models and how they may help predict
      treatment response in paediatric OCD.

PMID- 11466169
TI  - Paediatric autoimmune neuropsychiatric disorders associated with streptococcal
      infection (PANDAS).
AB  - The evidence to date, both published and unpublished, which addresses the
      validity of the proposed unique subgroup of children with early and abrupt onset
      of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to
      streptococcal infections was reviewed. The aetiology of OCD and tic disorders is
      unknown, although it appears that both disorders may arise from a variety of
      genetic and environmental factors. Post-streptococcal autoimmunity has been
      postulated as one possible mechanism for some. The acronym PANDAS (for paediatric
      autoimmune neuropsychiatric disorders associated with streptococcal infections)
      has been given to a subgroup of paediatric patients who meet five inclusionary
      criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden
      onset or episodic course of symptoms, temporal association between streptococcal
      infections and neuropsychiatric symptom exacerbations, and associated
      neurological abnormalities. The proposed model of pathophysiology provides for
      several unique treatment strategies, including the use of antibiotic prophylaxis
      to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory
      interventions (such as intravenous immunoglobulin or therapeutic plasma exchange)
      in the treatment severe neuropsychiatric symptoms. For the latter study group,
      long-term (2--5 yr) follow-up revealed continued symptom improvement for the
      majority of patients, particularly when antibiotic prophylaxis had been effective
      in preventing recurrent streptococcal infections. In addition, the episodic
      nature of the subgroup's illness provides for opportunities to study brain
      structure and function during health and disease, as well as allowing for
      investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune
      dysfunction in both OCD and tic disorders. Although much research remains to be
      done, an increasing body of evidence provides support for the postulate that OCD
      and tic disorders may arise from post-streptococcal autoimmunity. The unique
      clinical characteristics of the PANDAS subgroup, the presence of volumetric
      changes in the basal ganglia, and the dramatic response to immunomodulatory
      treatments, suggest that symptoms arise from a combination of local, regional and
      systemic dysfunction. Ongoing research is directed at understanding the nature of
      the abnormal immune response, as well as identifying at-risk children, in order
      to provide for novel strategies of prevention and treatment.

PMID- 11466170
TI  - Correlations between motor persistence and plasma levels in methylphenidate
      treated boys with ADHD.
AB  - Following a 0.9 mg/kg methylphenidate loading dose, serial plasma level
      determinations, self-scored mood ratings, and measures of motor persistence were
      gathered on eight previously unmedicated boys with attention deficit disorder
      with hyperactivity (ADHD) during a 9-h period. The measures were repeated using
      the same loading dose after 6 months of maintenance treatment with
      methylphenidate (1.3 mg/kg x d). Kinetic-dynamic modelling suggests inverse
      correlative relationships between motor performance errors and plasma levels.
      Pharmacokinetic parameters did not change between acute and maintenance drug
      treatment phases, and there was no evidence of long-term tolerance.

PMID- 11466172
TI  - Potential of polysaccharide anchored liposomes in drug delivery, targeting and
      immunization.
AB  - PURPOSE: Recently the emphasis has been laid upon the carbohydrate mediated
      liposomal interactions with the target cells. Among the various carbohydrate
      ligands, such as glycoproteins, glycolipids, viral proteins, polysaccharides,
      lipo-polysaccharides and other oligosaccharides, this review deals with the
      polysaccharide anchored liposomal system for their potential in drug delivery,
      targeting and immunization. Over the years, various strategies have been
      developed which include coating of the liposomal surface with natural or
      hydrophobized polysaccharides, namely mannan, pullulan, amylopectin, dextran
      etc., or their palmitoyl or cholesteroyl derivatives. The polysaccharide(s) coat
      tends vesicular constructs physicochemically stable in bio-environments and site
      specific. The aim of improving the physical and biochemical stability of
      liposomes and the ability to target liposomes to specific organs and cells, were
      the major attributes of the polysaccharide anchored liposomes. In this review the
      authors attempted to overview various applications of polysaccharide bearing
      liposomes, including lung therapeutics, targeted chemotherapy, cellular
      targeting, cellular or mucosal immunity and macrophage activation. Future
      prospects of the delivery module are also discussed. The review in general
      explores the concepts, options and opportunities of polysaccharide anchored
      liposomes with newer perspectives.

PMID- 11466173
TI  - Patterns of drug consumption in relation with the pathologies of elderly Mexican
      subjects resident in nursing homes.
AB  - PURPOSE: To describe the patterns of drugs consumed by the male and female
      elderly living in Mexican private and public nursing homes. METHODS: Three
      hundred and fifty elderly participants from four nursing homes (2 private and 2
      public) were selected for the six month study: 108 subjects were excluded; the
      remaining 242 were between 65 and 100 years old; 123 were females and 119 males.
      A complete clinical history was taken and clinical files were reviewed. RESULTS:
      Of the 242 elderly studied, 193 took diverse medications and 28.5% were at risk
      of some type of drug interaction. The groups of drugs more frequently consumed
      were vitamins and anti-anemic medications, followed by cardiovascular drugs.
      Females consumed greater number of drugs. They also consumed more drugs
      simultaneously. CONCLUSIONS: There is a need to monitor the elderly for their
      drugs pattern use.

PMID- 11466174
TI  - GHB: an important pharmacologic and clinical update.
AB  - Gamma-hydroxybutyrate (GHB) intoxication is a significant cause of morbidity and
      mortality in patients taking the drug for recreational purposes. Due to the
      recent increase in emergency room visits, hospital admissions, and deaths, it has
      become necessary to re-examine the pharmacology, pharmacokinetics,
      pharmacodynamics, clinical manifestations, and potential adverse effects
      associated with GHB use. We present an important pharmacologic and clinical
      update on GHB.

PMID- 11466175
TI  - An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition
      by garlic.
AB  - PURPOSE: Garlic has been used as a flavouring agent, traditional medicine, and
      functional food to improve physical or mental well-being. Garlic and garlic
      products generally have been regarded as safe but a number of conflicting reports
      in the literature and confounding factors make it difficult to unequivocally
      establish the clinical efficacy and safety of these products either alone or in
      the presence of therapeutic products. A preliminary study was undertaken with
      fresh garlic and garlic products using the major cDNA-expressed human cytochrome
      P-450 isozymes associated with the metabolism of HIV/AIDS drugs, and purified P
      glycoprotein (P-gp) cell membranes to ascertain the risk potential for generating
      interactions with therapeutic products. METHODS: A broad screening was undertaken
      with 10 garlic products (aged, odourless, oil, freeze-dried) and 3 varieties of
      fresh garlic bulbs (common, Elephant and Chinese), all purchased from local
      outlets, to examine their potential to affect human cytochrome P-450 2C9*1,
      2C9*2, 2C19, 2D6, 3A4, 3A5 and 3A7 mediated-metabolism of marker substrates using
      an in vitro fluorometric microtiter plate assay. Four garlic products were
      screened for their potential to interact with P-gp using an in vitro colourmetric
      ATPase assay. RESULTS: Extracts of fresh garlic, different brands and lots of
      odourless garlic and representative samples of garlic oil, freeze dried garlic,
      and aged garlic exhibited an inhibitory effect on cytochrome P450 2C9*1, 2C19,
      3A4, 3A5 and 3A7 mediated metabolism of a marker substrate. The activity of 2D6
      mediated-metabolism was generally unaffected by garlic. Extracts of the fresh
      garlic stimulated CYP2C9*2 metabolism of the marker substrate. With the extracts
      tested, garlic had very low to moderate P-gp interaction as compared with the
      positive control verapamil. CONCLUSIONS: Our in vitro findings demonstrate that
      garlic components can affect cytochrome P-450 2C, 2D and 3A mediated-metabolism
      of the isoforms studied. The safety and efficacy of conventional therapeutic
      products metabolized by the affected isozymes, particularly those with a narrow
      therapeutic index, taken concomitantly with garlic needs to be examined further
      under clinical settings.

PMID- 11466176
TI  - Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers
      in humans.
AB  - The beta-blockers comprise a group of drugs that are mostly used to treat
      cardiovascular disorders such as hypertension, cardiac arrhythmia, or ischemic
      heart disease. Each of these drugs possesses at least one chiral center, and an
      inherent high degree of enantioselectivity in binding to the beta-adrenergic
      receptor. For beta-blockers with a single chiral center, the (-) enantiomer
      possesses much greater affinity for binding to the beta-adrenergic receptors than
      antipode. The enantiomers of some of these drugs possess other effects, such as
      antagonism at alpha-adrenergic receptors or Class III antiarrhythmic activity.
      However, these effects generally display a lower level of stereoselectivity than
      the beta-blocking activity. Except for timolol, all of these drugs used
      systemically are administered clinically as the racemate. As a class, the beta
      blockers are quite diverse from a pharmacokinetic perspective, as they display a
      high range of values in plasma protein binding, percent of drug eliminated by
      metabolism or unchanged in the urine, and in hepatic extraction ratio. With
      respect to plasma concentrations attained after oral or intravenous dosing, in
      most cases the enantiomers of the beta-blockers show only a modest degree of
      stereoselectivity. However, the relative magnitude of the concentrations of the
      enantiomers in plasma is not constant in all situations and varies from drug to
      drug. Further, various factors related to the drug (e.g., dosing rate or
      enantiomer-enantiomer interaction) or the patient (e.g., racial background,
      cardiovascular function, or the patient metabolic phenotype) may affect the
      stereospecific pharmacokinetics and pharmacodynamics of beta-blockers. An
      understanding of the stereospecific pharmacokinetics and pharmacodynamics of beta
      blockers may help clinicians to interpret and predict differences among patients
      in pharmacologic responses to these drugs.

PMID- 11466177
TI  - A novel extractionless hplc fluorescence method for the determination of
      glyburide in the human plasma: application to a bioequivalence study.
AB  - PURPOSE: To develop a simple, sensitive and rapid HPLC fluorescence method with
      single step sample preparation for the determination of glyburide in the human
      plasma. METHODS: Glyburide and ketoconazole (internal standard) were extracted
      from the 0.5 mL plasma by addition of 0.5 mL acetonitrile and 50 microL CuSO(4)
      solution (5% w/v in water). The separation was achieved on the Kingsorb 3 microm,
      C8 reverse phase column at ambient temperature with a mobile phase consisted of
      45% buffer solution (0.05 M NH(4)H(2)P(4)), 40% acetonitrile and 15% methanol
      adjusted to pH 5.7 by diluted ammonia solution. A fluorescence detector was set
      at 235 nm excitation wavelength and 354 nm emission wavelengths to monitor eluted
      components. RESULTS: The internal standard and glyburide eluted at about 6.7 and
      9.6 min, respectively at the flow rate of 1 mL/min. The regression equation was
      established for every calibration curves (5 ng/mL to 400 ng/mL), which resulted
      in the correlation coefficient of 0.99 or greater. The absolute recovery ranged
      from 94.32 to 98.12% and the relative recovery ranged from 91.12 to 97.15%. The
      intraday coefficient of variation (CV) ranged from of 6.52 to 12.35% and interday
      varied from 6.21 to 16.07%. The limit of quantitation (LOQ) of glyburide was set
      to five ng/mL. CONCLUSION: This simple, rapid and sensitive method is suitable
      for pharmacokinetic, bioavailability and biequivalence studies.

PMID- 11466178
TI  - Varicella vaccination--a critical review of the evidence.

PMID- 11466180
TI  - Behaviour and developmental effects of otitis media with effusion into the teens.
AB  - OBJECTIVE: To examine whether behavioural or cognitive sequelae of otitis media
      with effusion (OME) continue into late childhood and the early teens (11-18
      years). SETTING: Data from a large multipurpose birth cohort study: the Dunedin
      multidisciplinary health and development study. PARTICIPANTS: Around 1000
      children from the study. The main independent variable of interest was otological
      status of the child up to age 9. MAIN OUTCOME MEASURES: Parent and teacher rated
      behaviour problems, including antisocial, neurotic, hyperactive, and inattentive
      behaviours, and tests of academic achievement including intelligence quotient
      (IQ), reading, and spelling were available in a high proportion of the cohort at
      ages 11 to 18 years. RESULTS: After adjustments for covariates such as
      socioeconomic status, hyperactive and inattentive behaviour problems were evident
      as late as 15 years, and lower IQ associated with OME remained significant to 13
      years. The largest effects were observed for deficits in reading ability between
      11 and 18 years. CONCLUSIONS: No previous study considering behaviour problems as
      an outcome has followed children long enough to determine whether some of the
      early sequelae of OME are still present in the early to late teens. Some
      developmental sequelae of OME, particularly deficits in reading ability, can
      persist into late childhood and the early teens.

PMID- 11466181
TI  - Does early detection of otitis media with effusion prevent delayed language
      development?
AB  - OBJECTIVE: To consider whether earlier detection of otitis media with effusion
      (OME) in asymptomatic children in the first 4 years of life prevents delayed
      language development. METHODS: MEDLINE and other databases were searched and
      relevant references from articles reviewed. Critical appraisal and consensus
      development were in accordance with the methods of the Canadian Task Force on
      Preventive Health Care. RESULTS: No randomised controlled trials assessing the
      overall screening for OME and early intervention to prevent delay in acquiring
      language were identified, although one trial evaluated treatment in a screened
      population and found no benefit. The "analytic pathway" approach was therefore
      used, where evidence is evaluated for individual steps in a screening process.
      The evidence supporting the use of tools for early detection such as
      tympanometry, microtympanometry, acoustic reflectometry, and pneumatic otoscopy
      in the first 4 years of life is unclear. Some treatments (mucolytics,
      antibiotics, steroids) resulted in the short term resolution of effusions as
      measured by tympanometry. Ventilation tubes resolved effusions and improved
      hearing. Ventilation tubes in children with hearing loss associated with OME
      benefited children in the short term, but after 18 months there was no difference
      in comparison with those assigned to watchful waiting. Most prospective cohort
      studies that evaluated the association between OME and language development
      lacked adequate measurement of exposure or outcome, or suffered from attrition
      bias. Findings with regard to the association were inconsistent. CONCLUSIONS:
      There is insufficient evidence to support attempts at early detection of OME in
      the first 4 years of life in the asymptomatic child to prevent delayed language
      development.

PMID- 11466183
TI  - Accidents and resulting injuries in premobile infants: data from the ALSPAC
      study.
AB  - BACKGROUND AND AIMS: Little is known about injuries resulting from accidents in
      premobile infants. We aimed to describe the pattern of minor accidents in infants
      and their resulting injuries. METHODS: The ALSPAC study collected data in
      successive postal questionnaires. At 6 months of age, parents were asked to
      describe any accident since birth. The type of fall, distance fallen, resulting
      injury, and help sought were independently coded. Burns were similarly coded.
      RESULTS: A total of 11 466 responses were available. In 2554 children, 3357 falls
      were reported; 53% fell from beds or settees and 12% fell from arms or while
      being carried. Only 14% reported visible injury, of which 56% were bruises; 97%
      of injuries specified involved the head. Only 21 falls (<1%) resulted in
      concussion or fracture. A burn or scald occurred in 172 cases (1.5%). The main
      causes of scalds were hot drinks and water, with contact burns caused by
      radiators, cookers, and hot food. CONCLUSIONS: Falls in young infants are common
      while burns are rare. Injuries from falls are infrequent, predominantly trivial,
      and almost entirely confined to the head. Falls from beds and settees did not
      result in skull fractures. Serious injury was the result of complex accidents.

PMID- 11466184
TI  - Changes in the epidemiological pattern of sudden infant death syndrome in
      southeast Norway, 1984-1998: implications for future prevention and research.
AB  - AIM: To look for changes in risk factors for sudden infant death syndrome (SIDS)
      after decrease and stabilisation of the SIDS rate. METHODS: Questionnaires were
      distributed to parents of 174 SIDS infants, dying between 1984 and 1998, and 375
      age and sex matched controls in southeast Norway. RESULTS: The proportion of
      infants sleeping prone has decreased, along with the decrease in SIDS rate for
      the region during the periods studied, but over half of the SIDS victims are
      still found in the prone position. As the number of SIDS cases has decreased,
      additional risk factors have become more significant. Thus, after 1993, a
      significantly increased risk of SIDS is seen when the mother smokes during
      pregnancy. After 1993, young maternal age carries an increased risk. Maternal
      smoking and young maternal age are associated with each other. For SIDS victims,
      an increase in the number of infants found dead while co-sleeping is seen, and
      the age peak between 2 and 4 months and the winter peak have become less
      pronounced. CONCLUSION: Changes in risk factor profile following the decrease in
      SIDS rate in the early 1990s, as well as consistency of other factors, provides
      further clues to SIDS prevention and to the direction of further studies of death
      mechanisms.

PMID- 11466185
TI  - Nasal and intrapulmonary haemorrhage in sudden infant death syndrome.
AB  - BACKGROUND: Fresh intrapulmonary and oronasal haemorrhages in cases of sudden
      infant death syndrome (SIDS) might be markers for accidental or intentional
      smothering inappropriately diagnosed as SIDS. AIM: To compare the incidence,
      epidemiological association, and inter-relation of nasal haemorrhage,
      intrapulmonary haemorrhage, and intrathoracic petechiae in infant deaths
      certified as SIDS. METHODS: In SIDS cases from a large nationwide case-control
      study, a wide range of variables were compared in cases with and without reported
      nasal haemorrhage and, in a subgroup of cases, in those with and without
      pathologically significant intrapulmonary haemorrhage. RESULTS: Nasal haemorrhage
      was reported in 60 of 385 cases (15%) whose parents were interviewed.
      Pathologically significant intra-alveolar pulmonary haemorrhage was found in 47%
      of 115 cases studied, but was severe in only 7%. Infants with nasal haemorrhage
      had more haemorrhage into alveoli and air passages than age matched cases without
      nasal haemorrhage. In multivariate analysis, nasal haemorrhage was associated
      with younger infant age, bed sharing, and the infant being placed non-prone to
      sleep. Intrapulmonary haemorrhage was associated with the same three factors in
      univariate analysis, but in multivariate analysis only younger infant age
      remained statistically significant. There was no significant association between
      nasal or intra-alveolar haemorrhages and intrathoracic petechiae. CONCLUSIONS:
      Nasal and intrapulmonary haemorrhages have common associations not shared with
      intrathoracic petechiae. Smothering is a possible common factor, although is
      unlikely to be the cause in most cases presenting as SIDS.

PMID- 11466186
TI  - Liquid paraffin: a reappraisal of its role in the treatment of constipation.

PMID- 11466187
TI  - Nationwide study of haemolytic uraemic syndrome: clinical, microbiological, and
      epidemiological features.
AB  - AIMS: To establish the incidence and aetiology of haemolytic uraemic syndrome
      (HUS) in Australia and compare clinical and microbial characteristics of sporadic
      and outbreak cases. METHODS: National active surveillance through the Australian
      Paediatric Surveillance Unit with monthly case notification from paediatricians,
      July 1994 to June 1998. Children under 15 years presenting with microangiopathic
      haemolytic anaemia, thrombocytopenia, and acute renal impairment were identified.
      RESULTS: Ninety eight cases were identified (incidence 0.64 per 10(5) children
      <15 years/annum and 1.35 per 10(5) children <5 years/annum). Eighty four were
      associated with diarrhoea (64 sporadic, 20 constituting an outbreak) and 14 were
      atypical. Shiga toxin producing Escherichia coli (STEC) O111:H- was the most
      common isolate in sporadic HUS and caused the outbreak. However O111:H- isolates
      from outbreak and sporadic cases differed in phage type and subtyping by DNA
      electrophoresis. STEC isolates from sporadic cases included O26:H-, O113:H21,
      O130:H11, OR:H9, O157:H-, ONT:H7, and ONT:H-. STEC O157:H7 was not isolated from
      any case. Only O111:H- isolates produced both Shiga toxins 1 and 2 and possessed
      genes encoding E coli attaching and effacing gene (intimin) and enterohemolysin.
      Outbreak cases had worse gastrointestinal and renal disease at presentation and
      more extrarenal complications. CONCLUSIONS: Linking national surveillance with a
      specialised laboratory service allowed estimation of HUS incidence and provided
      information on its aetiology. In contrast to North America, Japan, and the
      British Isles, STEC O157:H7 is rare in Australia; however, non-O157:H7 STEC cause
      severe disease including outbreaks. Disease severity in outbreak cases may relate
      to yet unidentified virulence factors of the O111:H- strain isolated.

PMID- 11466188
TI  - An evidence and consensus based guideline for acute diarrhoea management.
AB  - OBJECTIVE: To develop an evidence and consensus based guideline for the
      management of the child who presents to hospital with diarrhoea (with or without
      vomiting), a common problem representing 16% of all paediatric medical attenders
      at an accident and emergency department. Clinical assessment, investigations
      (biochemistry and stool culture in particular), admission, and treatment are
      addressed. The guideline aims to aid junior doctors in recognising children who
      need admission for observation and treatment and those who may safely go home.
      EVIDENCE: A systematic review of the literature was performed. Selected articles
      were appraised, graded, and synthesised qualitatively. Statements on
      recommendation were generated. CONSENSUS: An anonymous, postal Delphi consensus
      process was used. A panel of 39 selected medical and nursing staff were asked to
      grade their agreement with the generated statements. They were sent the papers,
      appraisals, and literature review. On the second and third rounds they were asked
      to re-grade their agreement in the light of other panelists' responses. Consensus
      was predefined as 83% of panelists agreeing with the statement. RECOMMENDATIONS:
      Clinical signs useful in assessment of level of dehydration were agreed.
      Admission to a paediatric facility is advised for children who show signs of
      dehydration. For those with mild to moderate dehydration, estimated deficit is
      replaced over four hours with oral rehydration solution (glucose based, 200-250
      mOsm/l) given "little and often". A nasogastric tube should be used if fluid is
      refused and normal feeds started following rehydration. Children at high risk of
      dehydration should be observed to ensure at least maintenance fluid is tolerated.
      Management of more severe dehydration is detailed. Antidiarrhoeal medication is
      not indicated. VALIDATION: The guideline has been successfully implemented and
      evaluated in a paediatric accident and emergency department.

PMID- 11466189
TI  - Persistent wheezing in infants with an atopic tendency responds to inhaled
      fluticasone.
AB  - BACKGROUND: The role of inhaled corticosteroids for the treatment of wheeze in
      infancy remains unclear. AIM: To investigate the effect of inhaled fluticasone on
      symptoms in a group of wheezy infants who had a high risk of progressing to
      childhood asthma. METHODS: A total of 52 infants, under 1 year of age, with a
      history of wheeze or cough and a history (personal or first degree relative) of
      atopy were prescribed either 150 microg fluticasone twice daily (group F) or
      placebo (group P), via metered dose inhaler, for 12 weeks following a two week
      run in period. Symptoms were scored in a parent held diary and the mean daily
      symptom score (MDS) and symptom free days (SFD) calculated for each two week
      period. RESULTS: Thirty seven infants completed the study. Both MDS and SFD
      improved significantly between the run in and final two week period in group F,
      but not group P, with a mean difference in change (95% CI) between groups of 1.12
      (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD.
      CONCLUSION: Improvement of clinical symptoms in response to fluticasone can be
      shown in this high risk group of infants. In the absence of effective
      alternatives inhaled corticosteroids should be considered in this patient group.

PMID- 11466191
TI  - Dipstick measurements of urine specific gravity are unreliable.
AB  - AIM: To evaluate the reliability of dipstick measurements of urine specific
      gravity (U-SG). METHODS: Fresh urine specimens were tested for urine pH and
      osmolality (U-pH, U-Osm) by a pH meter and an osmometer, and for U-SG by three
      different methods (refractometry, automatic readout of a dipstick (Clinitek-50),
      and (visual) change of colour of the dipstick). RESULTS: The correlations between
      the visual U-SG dipstick measurements and U-SG determined by a refractometer and
      the comparison of Clinitek((R))-50 dipstick U-SG measurements with U-Osm were
      less than optimal, showing very wide scatter of values. Only the U-SG
      refractometer values and U-Osm had a good linear correlation. The tested dipstick
      was unreliable for the bedside determination of U-SG, even after correction for U
      pH, as recommended by the manufacturer. CONCLUSIONS: Among the bedside
      determinations, only refractometry gives reliable U-SG results. Dipstick U-SG
      measurements should be abandoned.

PMID- 11466190
TI  - Photopheresis at onset of type 1 diabetes: a randomised, double blind, placebo
      controlled trial.
AB  - BACKGROUND: In recent years photopheresis, an extracorporeal form of
      photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has
      been claimed to be an effective form of immunomodulation. AIM: To evaluate its
      effect in type 1 diabetes we performed a double blind, controlled study using
      placebo tablets and sham pheresis in the control group. METHODS: A total of 49
      children, aged 10-18 years of age at diagnosis of type 1 diabetes were included;
      40 fulfilled the study and were followed for three years (19 received active
      treatment with photopheresis and 21 placebo treatment). RESULTS: The actively
      treated children secreted significantly more C peptide in urine during follow up
      than control children. C peptide values in serum showed corresponding differences
      between the two groups. The insulin dose/kg body weight needed to achieve
      satisfactory HbA1c values was always lower in the photopheresis group; there was
      no difference between the groups regarding HbA1c values during follow up. The
      treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in
      the actively treated group. There were no differences regarding weight or height,
      or episodes of infection between the two groups during follow up. CONCLUSION:
      Photopheresis does have an effect in addition to its possible placebo effect,
      shown as a weak but significant effect on the disease process at the onset of
      type 1 diabetes, an effect still noted after three years of follow up.

PMID- 11466192
TI  - Increased urinary leukotriene E(4) during febrile attacks in the
      hyperimmunoglobulinaemia D and periodic fever syndrome.
AB  - BACKGROUND: The hyperimmunoglobulinaemia D and periodic fever syndrome is a
      hereditary periodic fever, caused by deficiency of the enzyme mevalonate kinase.
      It is unclear how this defect leads to recurrent fever episodes. AIM: To assess
      the involvement of cysteinyl leukotrienes in the pathogenesis of fever attacks as
      reflected by urinary leukotriene E(4) (LTE(4)) excretion. METHODS: Urinary LTE(4)
      was measured in seven patients while febrile and afebrile. RESULTS: LTE(4) was
      raised during fever in all subjects (46-199 nmol/mol creatinine, mean 92; normal
      <40). Urinary LTE(4) was normal between attacks, as well as in normal children
      with fever as a result of miscellaneous causes. CONCLUSION: Our results suggest
      that cysteinyl leukotrienes play a role in the pathophysiology of this disorder.
      As no effective treatment is yet available, leukotriene receptor antagonists
      might offer a new therapeutic approach for patients with the
      hyperimmunoglobulinaemia D and periodic fever syndrome.

PMID- 11466193
TI  - Diagnostic assessment of haemorrhagic rash and fever.
AB  - AIMS: To establish criteria for early distinction between meningococcal disease
      and other conditions with similar clinical features, and to identify other causes
      for haemorrhagic rashes accompanied by fever. METHODS: In a prospective study,
      264 infants and children hospitalised with fever and skin haemorrhages were
      studied. RESULTS: We identified an aetiological agent in 28%: 15% had
      meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus
      infection, and 4% adenovirus infection. Five clinical variables distinguished
      between meningococcal disease and other conditions on admission: (1) skin
      haemorrhages of characteristic appearance; (2) universal distribution of skin
      haemorrhages; (3) maximum diameter of one or more skin haemorrhages greater than
      2 mm; (4) poor general condition (using a standardised observation scheme); and
      (5) nuchal rigidity. If any two or more of these clinical variables were present,
      the probability of identifying a patient with meningococcal disease was 97% and
      the false positive rate was only 12%. This diagnostic algorithm did not identify
      children in whom septicaemia was caused by other bacterial species.

PMID- 11466195
TI  - Correlates of prepubertal bone mineral density in cystic fibrosis.
AB  - AIM: To examine early factors in bone mineral accretion in cystic fibrosis (CF).
      METHODS: In 22 prepubertal children with CF and mild lung disease, the relation
      between total body bone mineral density (BMD) and measures of body composition,
      biochemistry, lung function, and physical activity was studied. RESULTS: There
      was a non-significant mild reduction in mean total body BMD. No relation was
      found between BMD and anthropometric indices, fat free soft tissue, degree of
      lung disease, degree of fat malabsorption, dietary energy intake, or level of
      physical activity. Significant impairments in physical growth were apparent in
      this population and were found to correlate with degree of lung disease.
      CONCLUSION: A CF specific factor appears unlikely to be associated with the
      osteopenia commonly found in CF. Careful attention to general aspects of
      lifestyle and nutrition is recommended to maximise bone mineral accretion in this
      population.

PMID- 11466198
TI  - Transgenic major histocompatibility complex class I antigen expressed in mouse
      trophoblast affects maternal immature B cells.
AB  - We have produced transgenic mice using the mouse placental lactogen type II
      promoter to force and restrict the expression of the mouse major
      histocompatibility complex (MHC) class I molecule, H-2K(b), to the placenta. We
      show that the transgenic MHC antigen H-2K(b) is expressed exclusively in
      trophoblast giant cells from Day 10.5 until the end of gestation. This expression
      affects neither the fetal development nor the maternal tolerance to the fetus in
      histoincompatible mothers. We have used the 3.83 B cell receptor (BcR) transgenic
      mouse line to follow the fate of H-2K(b)-specific maternal B cells in mothers
      bearing H-2K(b)-positive placentas. Our results suggest that transgenic H-2K(b)
      molecules on trophoblast giant cells are recognized by 3.83 BcR-transgenic B
      cells in the bone marrow of pregnant females. This antigen recognition triggers
      the deletion of a bone marrow B cell subpopulation, including immature and
      transitional B cells. Their percentage decreases during the second half of
      gestation and is down to 8% on Day 17.5, compared to 22% in the (3.83 Tg female x
      Fvb) control group. This deletion might contribute to the process of maternal
      tolerance of the conceptus.

PMID- 11466199
TI  - Follicle Selection in Cattle: Relationships among Growth Rate, Diameter Ranking,
      and Capacity for Dominance.
AB  - Follicles of wave 1 were designated F1, F2, and so forth, according to descending
      diameter at the expected (F1, > or =8.2 mm) or observed beginning of deviation
      (Hour 0), as indicated by a reduction in growth rate of F2. During Hours -24 to 0
      (experiment 1; n = 34 waves) and Hours -16 to 0 (experiment 2; n = 21), F1 and F2
      grew in parallel (no significant differences). During Hours -16 to 0, growth rate
      was greater (P < 0.05) for F1 (1.4 +/- 0.1 mm/16 h) and F2 (1.0 +/- 0.1) than for
      F3 (0.6 +/- 0.1) and F4 (0.5 +/- 0.1). During Hours 0 to 16, growth rate was
      greater (P < 0.05) for F1 (1.4 +/- 0.2 mm/16 h) than for F2 (0.1 +/- 0.1), F3
      (0.1 +/- 0.1), and F4 (0.1 +/- 0.2). In experiment 1, zero, one, two, or three
      largest follicles were ablated by aspiration of contents at Hour 0 (n = 7/group).
      For heifers with a single dominant follicle, the dominant follicle formed from
      the largest retained follicle more often when it was >7.0 mm (14 of 15) than when
      it was <7.0 mm (0 of 10). When the retained follicles were <7.0 mm, the first
      follicle to reach 7.0 mm became dominant in seven of eight heifers. Mean hour of
      observed deviation (occurring after Hour 0 in the ablation groups) increased
      progressively in groups with increasing number of ablated follicles. Plasma
      concentrations of FSH for groups with one, two, or three ablated follicles
      increased to a similar extent between Hours 0 and 12. Results supported the
      following: 1) during the 24 h before the beginning of deviation, small follicles
      grew more slowly than large follicles and the largest follicles grew in parallel;
      2) after ablation of large follicles, the small retained follicles did not
      deviate until one reached a diameter characteristic of the beginning of
      deviation; 3) the potential for dominance at the expected beginning of deviation
      was greatest for the largest follicle and decreased progressively for the smaller
      follicles but only when the retained follicles were >7.0 mm; and 4) the three
      largest subordinate follicles began to deviate simultaneously.

PMID- 11466200
TI  - Activity of a sperm-borne oocyte-activating factor in spermatozoa and
      spermatogenic cells from cynomolgus monkeys and its localization after oocyte
      activation.
AB  - It is widely accepted that mature mammalian oocytes are induced to resume meiosis
      by a sperm-borne oocyte-activating factor(s) (sperm factor, SF) immediately after
      normal fertilization or intracytoplasmic sperm injection. The SF is most likely a
      soluble factor that is localized within the cytoplasm of mature spermatozoa, but
      the exact stage at which it appears during spermatogenesis and its localization
      after oocyte activation is not fully understood, except in the mouse. First, we
      injected mature spermatozoa and spermatogenic cells from cynomolgus monkeys into
      mouse oocytes to assess their oocyte-activating capacity. More than 90% of mouse
      oocytes were activated after injection of monkey spermatozoa. Round spermatids
      and primary spermatocytes (late pachytene to diplotene) also activated oocytes
      (93% and 79%, respectively). Injection of monkey spermatozoa and spermatids
      induces intracellular Ca(2+) oscillations in a pattern similar to that seen
      following normal fertilization. Most spermatocytes did not produce typical
      intracellular Ca(2+) oscillations. Second, we transferred pronuclei or cytoplasts
      from mouse oocytes that had been activated by monkey spermatozoa or spermatids
      into intact mature mouse oocytes by electrofusion in order to examine the
      localization of the SF after pronuclear formation. Some of the SF was localized
      within the pronuclei, but some stayed in the ooplasm. This study demonstrated
      that spermatogenic cells of cynomolgus monkeys acquire oocyte-activating capacity
      at much earlier stages than those of mice, and that the monkey SF has a
      pronucleus-directing nature, although to a lesser extent than the mouse SF.

PMID- 11466201
TI  - Involvement of MEK-mitogen-activated protein kinase pathway in follicle
      stimulating hormone-induced but not spontaneous meiotic resumption of mouse
      oocytes.
AB  - Mitogen-activated protein (MAP) kinase has been reported to be activated during
      oocyte meiotic maturation in a variety of mammalian species. However, the
      mechanism(s) responsible for MAP kinase activation and the consequence of its
      premature activation during gonadotropin-induced oocyte meiotic resumption have
      not been examined. The present experiments were conducted to investigate the
      possible role of MAP kinase in FSH-induced and spontaneous oocyte meiotic
      resumption in the mouse. MAP kinase kinase (MAPKK, MEK) inhibitor, PD98059 or
      U0126, produced a dose-dependent inhibitory effect on both FSH-induced oocyte
      meiotic resumption and MAP kinase activation in the oocytes. However, the same
      inhibitor did not block spontaneous meiotic resumption of either denuded or
      cumulus cell-enclosed mouse oocytes, despite the activity of MAP kinase being
      totally inhibited. Immunoblotting the oocytes and the cumulus cells with the anti
      active MAP kinase antibody showed that MAP kinase activity in the oocytes was
      detected at 8 h of FSH treatment, prior to germinal vesicle breakdown and
      increased as maturation progressed in the following culture period. In the
      cumulus cells, MAP kinase was activated even faster, its activity was detected at
      1 h of FSH stimulation and increased gradually until 8 h of FSH treatment, then
      decreased and diminished after 12 h of FSH action. These data demonstrated that
      the MEK-MAP kinase pathway is implicated in FSH-induced but not spontaneous
      oocyte meiotic resumption.

PMID- 11466202
TI  - Temporal and spatial localization patterns of Gata4 during porcine gonadogenesis.
AB  - The zinc finger transcription factor Gata4, is associated with gonadal
      development in many species. The present study characterizes temporal and spatial
      localization of Gata4 throughout gonadogenesis in porcine embryos.
      Immunohistochemical studies illustrated that Gata4 protein is present in the
      coelomic epithelium prior to histological differentiation of the nascent
      bipotential gonad, marking the future site of both XX and XY porcine gonads. Many
      somatic cells of both XX and XY bipotential gonads continue to retain Gata4
      immunoreactivity throughout sexual differentiation and subsequent gonadal
      development. Testicular cords were evident by 26 days postcoitum. Gata4 was
      present in Sertoli cells, identified by virtue of coexpression with Mullerian
      inhibiting substance and also interstitial cells including Leydig cells
      throughout fetal and postnatal life. Many somatic cells of the differentiating
      ovary including follicular cells also contained Gata4 protein throughout fetal
      and postnatal life. Gata4 was not present in germ cells, endothelial cells, or
      other undifferentiated mesenchymal cells of both XX and XY gonads. A population
      of Gata4-positive cells in the dorsal mesentery was continuous with the coelomic
      epithelium of the gonad. This localization pattern led to the hypothesis that a
      subpopulation of somatic cells in the dorsal mesentery moves toward the gonad. An
      in vitro cell migration assay demonstrated that Gata4-positive cells
      preferentially migrate toward explanted gonadal tissue, and morphological
      features of the developing gonad supported this hypothesis. This study
      illustrates that Gata4 is a very early marker for gonad formation, highlights
      species differences in temporal and spatial localization patterns, and suggests a
      potential role for Gata4 in the development of both XX and XY porcine gonads.
      Further, we suggest that mesenchymal cells of the dorsal mesentery may provide a
      source of somatic cells that migrate and incorporate into the gonad and
      contribute to various somatic cell lineages. Overall, the spatial and temporal
      localization patterns of Gata4 during porcine gonadogenesis implies a much
      earlier and wider role for Gata4 than previously reported in other species.

PMID- 11466203
TI  - Characterization of fibroblastic cell plasticity in the lamina propria of the rat
      uterine cervix at term.
AB  - Different organs contain fibroblasts with specific features and functions,
      indicating the complexity of fibroblast biology. In the rat cervical stroma,
      fibroblasts are preferentially located in the fibrous ring that surrounds the
      mucous layer. The purpose of this study was to investigate the morphological
      features and immunophenotype of fibroblastic cells of the uterine cervix in
      cycling, pregnant, and postpartum rats. Expression of the cytoskeletal proteins
      desmin, vimentin, and alpha-smooth muscle actin (alpha-SMA) were studied by
      immunohistochemistry. The optical density of immunohistochemical staining was
      quantified by image analysis. The ultrastructural features of fibroblastic cells
      were observed under transmission electron microscopy. Cervical fibroblastic cells
      always expressed vimentin and desmin but never alpha-SMA. During the first half
      of pregnancy (Day 5 [D5] to D14), desmin intensity values were similar to those
      of cycling and postpartum fibroblasts. In contrast, a strong expression of desmin
      was found from D15 to D22, with maximal expression at term (D23).
      Immunohistochemical expression for vimentin was constant throughout pregnancy and
      showed no differences with cycling and postpartum uterine cervices. Stromal cells
      from cycling and early pregnant rats displayed ultrastructural features
      characteristic of typical fibroblasts. In contrast, at the end of pregnancy,
      fibroblasts differentiated and showed increased secretory characteristics,
      reaching the ultrastructural features of a myofibroblast. Based on the
      differential expression of desmin and the electron microscopic observations, the
      foregoing results showed a modulation of the fibroblastic phenotype in the
      uterine cervix during pregnancy. To our knowledge, this is the first report that
      addresses the presence of myofibroblasts derived from resident fibroblasts in the
      fibrous ring of the rat uterine cervix. Fibroblastic-myofibroblastic cell
      plasticity may have implications in the physiological changes displayed in the
      uterine cervix during pregnancy, parturition, and postpartum involution.

PMID- 11466204
TI  - Aquaporin 9 expression along the male reproductive tract.
AB  - Fluid movement across epithelia lining portions of the male reproductive tract is
      important for modulating the luminal environment in which sperm mature and
      reside, and for increasing sperm concentration. Some regions of the male
      reproductive tract express aquaporin (AQP) 1 and/or AQP2, but these transmembrane
      water channels are not detectable in the epididymis. Therefore, we used a
      specific antibody to map the cellular distribution of another AQP, AQP9 (which is
      permeable to water and to some solutes), in the male reproductive tract. AQP9 is
      enriched on the apical (but not basolateral) membrane of nonciliated cells in the
      efferent duct and principal cells of the epididymis (rat and human) and vas
      deferens, where it could play a role in fluid reabsorption. Western blotting
      revealed a strong 30-kDa band in brush-border membrane vesicles isolated from the
      epididymis. AQP9 is also expressed in epithelial cells of the prostate and
      coagulating gland where fluid transport across the epithelium is important for
      secretory activity. However, it was undetectable in the seminal vesicle,
      suggesting that an alternative fluid transport pathway may be present in this
      tissue. Intracellular vesicles in epithelial cells along the reproductive tract
      were generally poorly stained for AQP9. Furthermore, the apical membrane
      distribution of AQP9 was unaffected by microtubule disruption. These data suggest
      that AQP9 is a constitutively inserted apical membrane protein and that its cell
      surface expression is not acutely regulated by vesicular trafficking. AQP9 was
      detectable in the epididymis and vas deferens of 1-wk postnatal rats, but its
      expression was comparable with adult rats only after 3--4 wk. AQP9 could provide
      a route via which apical fluid and solute transport occurs in several regions of
      the male reproductive tract. The heterogeneous and segment-specific expression of
      AQP9 and other aquaporins along the male reproductive tract shown in this and in
      our previous studies suggests that fluid reabsorption and secretion in these
      tissues could be locally modulated by physiological regulation of AQP expression
      and/or function.

PMID- 11466205
TI  - Adenosine triphosphate-binding cassette superfamily transporter gene expression
      in severe male infertility.
AB  - Cystic fibrosis transmembrane regulator (CFTR), multidrug-resistant (MDR)1, and
      multidrug resistance-associated (MRP) proteins belong to the ATP-binding cassette
      (ABC) transporter superfamily. A compensatory regulation of MDR1 and CFTR gene
      expression has been observed in CFTR knockout rodent intestine and in an
      epithelial cell line of human colon, whereas a high homology and similar anion
      binding site are shared by MRP and CFTR proteins. To provide better insight into
      the relationship among the expression behavior in vivo of the three genes in
      human testis, analysis of MDR1 and MRP gene expression in testicular biopsies was
      performed and related to the presence of CFTR gene mutations in congenital
      absence of the vas deferens (CAVD: n = 20) and non-CAVD (n = 30) infertile
      patients with azoospermia or severe oligozoospermia. A CFTR mutation analysis
      performed in both groups of patients supported the involvement of CFTR gene
      mutations in CAVD phenotype (85%) and in defective spermatogenesis (19%).
      Quantitative reverse transcription-polymerase chain reaction analysis of
      testicular tissue showed a CFTR-independent MDR1 and MRP gene expression in human
      testis, suggesting that the mechanisms underlying CFTR gene regulation in testis
      are different from those in intestine. These findings should contribute to the
      understanding of patterns of in vivo expression of CFTR, MDR1, and MRP genes in
      CFTR-related infertility.

PMID- 11466206
TI  - Oxytocin and lysophosphatidic acid induce stress fiber formation in human
      myometrial cells via a pathway involving Rho-kinase.
AB  - The actin cytoskeleton is important for stress fiber formation and contributes to
      the initiation and maintenance of smooth muscle contraction. To determine if
      oxytocin and lysophosphatidic acid (LPA) induce stress fiber formation, cultured
      human myometrial cells were exposed to oxytocin (10(-5) M) or LPA (10(-6) M), and
      filamentous (F) and globular (G) actin pools were stained with fluorescein
      isothiocyanate-phalloidin and Texas red DNase I, respectively. The F- to G-actin
      fluorescent-staining ratio was measured by fluorescence microscopy. Oxytocin and
      LPA increased stress fiber formation, as indicated by an increase in the F- to G
      actin fluorescent-staining ratio. The Rho-kinase inhibitor Y-27632 markedly
      attenuated this increase. Oxytocin-induced stress fiber formation was completely
      inhibited in the presence of the oxytocin antagonist compound VI. Tyrosine kinase
      inhibition with tyrphostin A23 partially blocked the increase induced by oxytocin
      but had no effect on LPA-induced stress fiber formation. Stress fiber formation
      was not blocked by pertussis toxin, mitogen-activated protein kinase, or protein
      kinase C inhibitors. Our results show that human myometrial cells respond to
      oxytocin and LPA with the formation of stress fibers that may be involved in the
      maintenance of uterine contractions. Rho-kinase appears to be a key signaling
      factor in this pathway.

PMID- 11466207
TI  - Use of cryopreserved pronuclear embryos for the production of transgenic mice.
AB  - A series of experiments was conducted to test the hypothesis that an improved
      cryopreservation protocol for pronuclear stage mouse embryos will produce
      transgenic (Tg) mice by pronuclear gene injection at a rate not significantly
      different from noncryopreserved embryos. In the first experiment, three
      cryoprotective agents (CPAs) (dimethyl sulfoxide [DMSO], propylene glycol [PG],
      ethylene glycol [EG]) and two cryopreservation protocols, currently used for
      pronuclear embryos, were compared in regard to their ability to maintain post
      thaw morphological integrity and in vitro developmental competence. In the second
      and third experiments, the optimal cryopreservation protocol determined from the
      first experiment was used to evaluate in vitro developmental competence of
      pronuclear embryos following green fluorescence protein gene injection and in
      vivo developmental competence as well as the gene integration rates. Survival
      (morphological integrity and development to two cells) of embryos cryopreserved
      in the presence of DMSO was higher (P < 0.05) than those cryopreserved with
      either PG or EG. Postinjection developmental competence (development to two
      cells) of cryopreserved CBA, C57B6/JxCBA-F1 and noncryopreserved (control)
      embryos was not different (P > 0.05). Postinjection blastocyst formation rate of
      cryopreserved and noncryopreserved C57B6/JxCBA-F1 embryos was similar (P > 0.05);
      however, noncryopreserved CBA embryos resulted in a higher blastocyst formation
      than controls (P < 0.05). While there was no difference in the percentage of
      transgenic fetuses between cryopreserved and control CBA embryos (P > 0.05),
      cryopreserved C57B6/JxCBA-F1 embryos resulted in lower transgenic fetuses than
      control (P < 0.05). These results indicate that the use of cryopreserved mouse
      pronuclear embryos can be a useful and efficient approach to the production of Tg
      mice.

PMID- 11466208
TI  - Developmental potential of mouse embryos reconstructed from metaphase embryonic
      stem cell nuclei.
AB  - Mice have recently been successfully cloned from embryonic stem (ES) cells.
      However, these fast dividing cells provide a heterogeneous population of donor
      nuclei, in terms of cell cycle stage. Here we used metaphases as a source of
      donor nuclei because they offer the advantage of being both unambiguously
      recognizable and synchronous with the recipient metaphase II oocyte. We showed
      that metaphases from ES cells can provide a significantly higher development rate
      to the morula or blastocyst stage (56--70%) than interphasic nuclei (up to 28%)
      following injection into a recipient oocyte. Selective detachment of mitotic
      cells after a demecolcin treatment greatly facilitates and accelerates the
      reconstruction of embryos by providing a nearly pure population of cells in
      metaphase and did not markedly affect the developmental rate. Most of the
      blastocysts obtained by this procedure were normal in terms of both morphology
      and ratio of inner cell mass and total cell number. After transfer into
      pseudopregnant recipients at the one- or two-cell stage, the ability of metaphase
      to be fully reprogrammed was demonstrated by the birth of two pups (1.5% of
      activated oocytes). Although the implantation rate was quite high (up to 32.9% of
      activated oocytes), the postimplantation development was characterized by a high
      and rapid mortality. Our data provide a clear situation to explore the long
      lasting effects that can be induced by early reprogramming events.

PMID- 11466209
TI  - Semenogelin II gene is replaced by a truncated line 1 repeat in the cotton-top
      tamarin.
AB  - The human seminal vesicles secrete two proteins, semenogelin I and semenogelin
      II, at very high concentrations. It has previously been shown that the cotton-top
      tamarin (Sanguinus oedipus), a New World monkey, is lacking the semenogelin II
      gene. We have now determined the nucleotide sequence of DNA located 5--13
      kilobases (kb) downstream of the tamarin semenogelin I gene---a region that in
      man is occupied by the semenogelin II gene. Two regions with homology to the
      human semenogelin II gene were identified in the tamarin DNA. The first region,
      of 3.5 kb, is homologous to DNA upstream of the human gene, and the second
      region, of 0.6 kb, is mainly derived from the second intron. Between these
      regions, equivalent to 594 base pairs (bp) upstream of the transcription
      initiation site to 12 bp downstream of the stop codon in the human semenogelin II
      gene, the cotton-top tamarin DNA carries a truncated LINE1 repeat. In another set
      of experiments, the tamarin DNA hybridizing to the mouse semenoclotin gene was
      investigated. It was concluded that hybridization is with the second intron of
      the semenoclotin gene, but very likely, the material does not represent a cotton
      top tamarin semenoclotin gene. Thus, a mammalian ancestor probably carried a
      single gene that in the rodent lineage developed into the semenoclotin gene and
      in the primate lineage into a progenitor of the semenogelin genes.

PMID- 11466210
TI  - Response of estradiol and inhibin to experimentally reduced luteinizing hormone
      during follicle deviation in mares.
AB  - The increase in LH concentrations at the time of the decrease in FSH
      concentrations during follicle deviation in mares was studied to determine the
      role of LH in the production of estradiol and immunoreactive inhibin (ir
      inhibin). Ten days after ovulation, all follicles > or =6 mm were ablated,
      prostaglandin F(2 alpha) was given, and either 0 mg (control group, n = 15) or
      100 mg of progesterone in safflower oil (treated group, n = 16) was given daily
      for 14 days, encompassing the day of diameter deviation. The follicular and
      hormonal data were normalized to the expected day of the beginning of diameter
      deviation when the largest follicle first reached > or =20 mm (Day 0). The
      experimentally induced decrease in LH concentrations during follicle deviation
      beginning on Day -4 delayed and stunted the increase in circulating
      concentrations of ir-inhibin and estradiol beginning on Days -3 and -1,
      respectively, but did not alter the predeviation FSH surge and the initiation of
      diameter deviation between the two largest follicles. Combined for both groups,
      the interval to the expected day of deviation was 16.6 days after ovulation when
      the largest follicle was a mean of 21.6 mm. After deviation, the largest follicle
      started to regress in the treated group beginning on Day 1 and was associated
      with decreased concentrations of ir-inhibin and estradiol, and increased
      concentrations of FSH. The negative influence of the dominant follicle on the
      postdeviation decrease in FSH observed in the control group was alleviated and
      concentrations resurged in the treated group. Apparently this is the first in
      vivo evidence that the increase in LH that precedes follicle deviation has a
      positive effect in supporting the production of inhibin during diameter
      deviation. It was concluded that the increase in LH concentrations before
      diameter deviation played a role in the production of estradiol and inhibin by
      the largest follicle during deviation.

PMID- 11466211
TI  - Luteolytic effect of prolactin is dependent on the degree of differentiation of
      luteal cells in the rat.
AB  - We studied the morphological and quantitative changes in cyclic corpora lutea
      (CCL) and in CL of pregnancy (CLP) during structural luteolysis. Elimination of
      CCL takes several cycles, and cell death occurs as successive apoptotic bursts,
      from 2100 h in proestrus to 1300 h in estrus. Each apoptotic burst determined a
      60% decrease in the CL volume and an 80% decrease in the number of steroidogenic
      cells (SC). All these changes were inhibited by blocking the preovulatory
      prolactin (PRL) surge with bromocryptine (CB154). Neither apoptotic cells nor
      changes in the number of SC were found in regressing CLP from Day 21 of pregnancy
      to Day 2 postpartum, although there was a 50% decrease in the CLP volume and a
      30% decrease in the mean cross-sectional area of SC. Treatment with CB154 on the
      day of parturition did not modify these regressive changes. On Day 5 postpartum,
      the volume of the CLP and the number of SC were equivalent in lactating rats
      (showing high PRL concentrations induced by pup suckling) and nonlactating
      noncycling rats (in which cyclicity and, therefore PRL surges, were blocked by
      treatment with LHRH antagonist). However, on Day 10 postpartum, the CLP volume
      and the number of SC were significantly decreased in lactating rats, and
      apoptotic cells were frequent. In postpartum cycling rats, the CLP did not show
      apoptotic cells on the day of the second postpartum estrus (on Day 5 postpartum),
      whereas on the day of the third postpartum estrus (on Day 9 postpartum),
      apoptotic cells were abundant. These results indicate that PRL does not induce
      apoptosis in the CLP before Day 5 postpartum and strongly suggest that the
      proapoptotic effect of PRL is dependent on the degree of differentiation of
      luteal cells.

PMID- 11466212
TI  - Inhibition of phosphatidylinositol 3-kinase or mitogen-activated protein kinase
      kinase leads to suppression of p34(cdc2) kinase activity and meiotic progression
      beyond the meiosis I stage in porcine oocytes surrounded with cumulus cells.
AB  - In this study, the effects of U0126 that inhibits the activity of mitogen
      activated protein (MAP) kinase kinase (MEK), and LY294002, which is a
      phosphatidylinositol (PI) 3-kinase inhibitor, on meiotic progression beyond the
      metaphase I (MI) stage in porcine oocytes were examined. Cumulus-oocyte complexes
      (COCs) were cultured for 22 h with 50 microM LY294002 or 10 microM U0126
      following cultivation for the initial 22 h. MAP kinase activity in oocytes
      cultured with LY294002 or U0126 was significantly lower than that in control
      oocytes cultured for up to 44 h. U0126 and LY294002 significantly decreased
      p34(cdc2) kinase activity and the proportion of oocytes reaching the MII stage
      compared to those in control oocytes. Oocytes denuded after COCs had been
      cultured for 22 h were cultured further for 22 h with U0126 or LY294002. In the
      denuded oocytes, U0126 suppressed MAP kinase activity, p34(cdc2) kinase activity,
      and meiotic progression to the MII stage; however, LY294002 did not significantly
      affect the activity of these kinases and meiotic progression. These results
      suggest that increasing MAP kinase activity in oocytes via the PI 3-kinase
      signaling pathway in cumulus cells is involved in the stimulation of maturation
      promoting factor, leading to meiotic progression beyond the MI to MII stage in
      porcine oocytes.

PMID- 11466213
TI  - Two new male contraceptives exert their effects by depleting germ cells
      prematurely from the testis.
AB  - The three currently available male contraceptive approaches are 1) the barrier
      method such as the condom, 2) hormonal methods by disrupting the pituitary
      testicular axis so as to impair spermatogenesis, and 3) immunological methods by
      preparing vaccines against male-specific antigens. We hereby describe an
      alternative approach in which attachments of developing germ cells onto the
      seminiferous epithelium are disrupted, thereby inducing their premature release
      into the tubular lumen. This in turn leads to infertility. A panel of analogues
      based on the core structure of 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid
      was synthesized. These compounds were subjected to an in vivo screening assay
      assessing their effects in inducing the expression of testin, a testicular marker
      whose expression correlates with the integrity of Sertoli-germ cell junctions. An
      induction of testin expression in the testis signifies a disruption of Sertoli
      germ cell junctions that is followed by depletion of germ cells from the
      seminiferous epithelium. Two compounds, namely 1-(2,4-dichlorobenzyl)-indazole-3
      carbohydrazide (AF-2364) and 1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid (AF
      2785), were identified that caused detachment of germ cells, in particular round
      and elongated spermatids, from the epithelium inducing their premature release
      into the tubular lumen as confirmed by histological analysis. Adult rats
      receiving several oral doses of either one of these compounds became infertile
      within 3-7 wk after the epididymal sperm reserve was exhausted. Depending on the
      dosing of the administered compound, rats became infertile for 4-14 wk before
      their fertility gradually bounced back, illustrating the reversibility and
      efficacy of these new compounds. Also, these compounds did not appear to impair
      the hypothalamus-pituitary-testicular axis because the serum levels of LH, FSH,
      and testosterone of the treated animals did not change significantly when
      compared to control rats. In addition, results of serum microchemistry illustrate
      that liver and kidney function was not affected in animals treated with both
      compounds.

PMID- 11466214
TI  - Evaluation of in vitro capacitation of stallion spermatozoa.
AB  - The primary aim of this study was to establish a flow cytometric technique for
      determining the capacitation status of stallion spermatozoa. To this end, a flow
      cytometric technique that demonstrates changes in plasma membrane fluidity;
      namely, merocyanine 540 staining, was compared with the more conventional Ca(2+)
      dependent fluorescence microscopic technique, chlortetracycline (CTC) staining,
      for assessing capacitation status. In addition, the effect of bicarbonate/CO(2)
      on the progress of capacitation and the acrosome reaction (AR) and on temporal
      changes in sperm motility, with particular regard to hyperactivation, was
      analyzed. For the study, fresh semen was washed and then incubated for 5 h in
      bicarbonate-containing or bicarbonate-free medium, with or without Ca(2+)
      ionophore to induce the AR, and at intervals during incubation aliquots were
      taken and analyzed for capacitation and acrosome status. The AR was assessed
      using both the CTC and fluorescein isothiocyanate-peanut agglutinin (FITC-PNA)
      staining techniques with similar results. In brief, it was found that merocyanine
      540 detects capacitation-related changes much earlier than CTC does (0.5 h versus
      approximately 3 h), and that flow cytometry for evaluation of capacitation and AR
      was a quicker (10 sec per sample) and more accurate (10,000 cells counted)
      technique than fluorescence microscopy. Furthermore, it was observed that Ca(2+)
      ionophore could not induce the AR in the absence of bicarbonate, but that the
      ionophore synergized the bicarbonate-mediated induction of the AR as detected by
      CTC (although it was not significant when evaluated using FITC-PNA). The
      percentage of hyperactive sperm in each sample was not affected by time of
      incubation under the experimental conditions studied. In conclusion, merocyanine
      540 staining is a better method than CTC staining for evaluating the early events
      of capacitation for stallion spermatozoa incubated in vitro. Furthermore,
      bicarbonate sperm activation clearly plays a vital role in the induction of the
      AR in stallion spermatozoa.

PMID- 11466215
TI  - Dominant bovine ovarian follicular cysts express increased levels of messenger
      RNAs for luteinizing hormone receptor and 3 beta-hydroxysteroid dehydrogenase
      delta(4),delta(5) isomerase compared to normal dominant follicles.
AB  - The objective was to compare ovarian steroids and expression of mRNAs encoding
      cytochrome P450 side-chain cleavage, cytochrome P450 17 alpha-hydroxylase,
      cytochrome P450 aromatase, 3 beta-hydroxysteroid dehydrogenase Delta(4),Delta(5)
      isomerase, LH, and FSH receptors and estrogen receptor-beta in ovaries of cows
      with dominant and nondominant ovarian follicular cysts and in normal dominant
      follicles. Estradiol-17 beta, progesterone, and androstenedione concentrations
      were determined in follicular fluid using specific RIAs. Dominant cysts were
      larger than young cysts or dominant follicles, whereas nondominant cysts were
      intermediate. Estradiol-17 beta (ng/ml) and total steroids (ng/follicle) were
      higher in dominant cysts than in dominant follicles. Expression of LH receptor
      and 3 beta-hydroxysteroid dehydrogenase mRNAs was higher in granulosa cells of
      dominant cysts than in dominant follicles. Nondominant cysts had higher
      follicular concentrations of progesterone, lower estradiol-17 beta
      concentrations, and lower expression of steroidogenic enzyme, gonadotropin
      receptor, and estrogen receptor-beta mRNAs than other groups. In summary,
      increased expression of LH receptor and 3 beta-hydroxysteroid dehydrogenase mRNAs
      in granulosa and increased follicular estradiol-17 beta concentrations were
      associated with dominant cysts compared to dominant follicles. Study of cysts at
      known developmental stages is useful in identifying alterations in follicular
      steroidogenesis.

PMID- 11466216
TI  - Follicular stage-dependent tumor necrosis factor alpha-induced hen granulosa cell
      integrin production and survival in the presence of transforming growth factor
      alpha in vitro.
AB  - The link between cell adhesion to extracellular matrix and integrin-mediated
      survival signals has been established in several physiological systems, and roles
      for the cytokines tumor necrosis factor alpha (TNF alpha) and transforming growth
      factor alpha (TGF alpha) have been suggested. TGF alpha stimulates fibronectin
      production in hen granulosa cells and is an important survival factor during
      follicular maturation. In contrast, the role of TNF alpha and its possible
      interaction with TGF alpha in the regulation of granulosa cell fate (death versus
      survival) during ovarian follicular development have not been fully elucidated.
      The object of the current study was to determine if TNF alpha and TGF alpha
      interact in the regulation of hen granulosa cell fibronectin and integrin content
      in the context of cell death and survival during follicular development. TGF
      alpha (0.1 or 10 ng/ml), but not TNF alpha (0.1 or 10 ng/ml), increased both
      cellular and secreted fibronectin content in granulosa cell cultures of F5,6 but
      not F1 follicles. The expression of integrin beta(3) subunit was also stimulated
      by TGF alpha in a follicular stage-dependent manner, and culture of F5,6
      granulosa cells with TNF alpha in the presence of maximal stimulatory
      concentrations of TGF alpha potentiated this response. TGF alpha increased both
      F5,6 and F1 granulosa cell [(3)H]thymidine incorporation but not 3-(4,5
      dimethylthiazol-2-yl)3,5-diphenyl tetrazolium bromide (MTT) metabolism. Although
      TNF alpha had no effect on [(3)H]thymidine incorporation irrespective of the
      presence of the growth factor, MTT metabolism was higher in F5,6 granulosa cells
      cultured for 24 h with both TNF alpha and TGF alpha than with either cytokine
      alone. Incubation of F5,6 granulosa cells for 48 and 72 h resulted in a TGF alpha
      inhibited loss of cellular adhesion and detachment of granulosa cells from the
      growth surface. Although TNF alpha alone had no effect on cell morphology, it
      facilitated the reorganization of the granulosa cells into multicellular follicle
      like structures in the presence of the growth factor. DNA degradation
      significantly increased between 0 and 72 h of culture in the absence of the
      cytokine but was suppressed by the addition of TGF alpha but not of TNF alpha.
      However, fluorometric analysis indicated that the primary type of cell death
      exhibited by F5,6 granulosa cells during extended culture and attenuated by the
      presence of TNF alpha and TGF alpha was necrosis and not apoptosis. The current
      study demonstrates that TNF alpha and TGF alpha interact in the regulation of
      granulosa cell integrin content and cell survival in vitro in a follicular stage
      dependent manner. These findings suggest that follicular development is
      accompanied by a change in the intraovarian role of TNF alpha; it is atretogenic
      prior to follicular selection but prevents follicular demise during preovulatory
      growth.

PMID- 11466217
TI  - MSJ-1, a mouse testis-specific DnaJ protein, is highly expressed in haploid male
      germ cells and interacts with the testis-specific heat shock protein Hsp70-2.
AB  - The MSJ-1 gene encodes a murine DnaJ homologue that is expressed specifically in
      adult testis. DnaJ proteins act as cochaperones of Hsp70 proteins in promoting
      diverse cellular functions. In this study we used recombinant MSJ-1 proteins to
      produce MSJ-1 antiserum and to carry out in vitro binding assays. In a wide
      immunoscreening of mouse tissues, affinity-purified MSJ-1 antibodies recognize a
      unique protein of 30 kDa in male germ cells only. MSJ-1 is able to interact with
      the testis-specific Hsp70-2 protein and can be coimmunoprecipitated with Hsp70-2
      from spermatogenic cells; binding of these two chaperones is consistent with the
      presence of a third component, which is so far unknown. MSJ-1 is weakly detected
      in early round spermatids, and its protein content increases in
      cytodifferentiating spermatids where it colocalizes with the developing acrosome
      and their postnuclear region. Hsp70-2, which is known to be highly expressed in
      meiotic cells, shows a subcellular localization in late differentiating
      spermatids that overlaps that of MSJ-1. MSJ-1 is also maintained in testicular
      and epididymal spermatozoa, where it sharply demarcates into two distinct cell
      areas; the outer surface of the acrosomal vesicle, and the centrosomal area. On
      the whole, our findings are consistent with a role for MSJ-1 in acrosome
      formation and centrosome adjustment during spermatid development, whereas its
      presence in mature spermatozoa suggests a special function during fertilization,
      shortly afterward, or both.

PMID- 11466218
TI  - Platelet-derived growth factor stimulates phospholipase C-gamma 1, extracellular
      signal-regulated kinase, and arachidonic acid release in rat myometrial cells:
      contribution to cyclic 3',5'-adenosine monophosphate production and effect on
      cell proliferation.
AB  - In the present study, we examined downstream signaling events that followed
      exposure of cultured rat myometrial cells to platelet-derived growth factor
      (PDGF) and their effect on cell proliferation. PDGF-BB induced tyrosine
      phosphorylation of PDGF-beta receptors and increased inositol trisphosphate
      production via the tyrosine phosphorylation of phospholipase (PL)C-gamma 1. PDGF
      BB also increased cAMP synthesis. This increase was potentiated by forskolin and
      reduced by indomethacin, a cyclooxygenase inhibitor, reflecting a Gs protein
      mediated process via prostaglandin biosynthesis. The prostaglandin produced by
      PDGF was characterized as prostacyclin (PGI(2)). PDGF-BB increased arachidonic
      acid (AA) release, which, similarly to cAMP accumulation, was abolished in the
      presence of AACOCF3, a cytosolic PLA(2) inhibitor, and in the absence of Ca(2+).
      U-73122, a potent inhibitor of PLC activity, blocked both the production of
      inositol phosphates and the AA release triggered by PDGF-BB. Extracellular signal
      regulated kinases (ERKs) 1 and 2 are expressed in myometrial cells, and PDGF-BB
      selectively activated ERK2. PD98059, an inhibitor of the ERK-activating kinase,
      blocked PDGF-BB-mediated ERK2 activation, AA release, and cAMP production. The
      results demonstrate that PDGF-BB stimulated cAMP formation through both PLC
      activation and ERK-dependent AA release and PGI(2) biosynthesis. PDGF-BB also
      increased cell proliferation and [(3)H]thymidine incorporation. This was
      abolished by PD98059, demonstrating that the ERK cascade is required for the
      mitogenic effect of PDGF-BB. Forskolin, which potentiated the cAMP response to
      PDGF-BB, attenuated both DNA synthesis and ERK activation triggered by PDGF-BB,
      suggesting the presence of a negative feedback regulation.

PMID- 11466219
TI  - Presence of the acute phase protein, bikunin, in the endometrium of gilts during
      estrous cycle and early pregnancy.
AB  - Noninvasive, epitheliochorial placental attachment in the pig is regulated
      through endometrial production of protease inhibitors. The objective of the
      present study was to determine if the light-chain serine protease inhibitor of
      the inter-alpha-trypsin inhibitor family, bikunin, is produced by the porcine
      endometrium during the estrous cycle and early pregnancy. Western blot analysis
      revealed the presence of bikunin in uterine flushings of gilts collected during
      the luteal phase of the estrous cycle and early pregnancy (Days 12-18). However,
      bikunin unbound to the inter-alpha-trypsin heavy chains was detected only in
      endometrial explant culture medium obtained from estrus and pregnant (Days 12,
      15, and 18) gilts. Endometrial bikunin gene expression was lowest on Day 10 of
      the estrous cycle and pregnancy, followed by a 30- to 77-fold increase on Day 15
      of the estrous cycle and pregnancy. Bikunin gene expression decreased on Day 18
      of the estrous cycle, whereas endometrial bikunin gene expression continued to
      increase in pregnant gilts. Bikunin mRNA was localized to the uterine glands
      between Days 15 and 18 of the estrous cycle and pregnancy. In addition to its
      role as a protease inhibitor, bikunin functions in stabilization of the
      extracellular matrix, which suggests that bikunin could be involved with
      facilitating placental attachment to the uterine epithelial surface in the pig.

PMID- 11466220
TI  - Nitric oxide promotes germ cell necrosis in the delayed phase after experimental
      testicular torsion of rat.
AB  - The purpose of this study is to determine whether inducible nitric oxide synthase
      (iNOS) is involved in the pathogenesis of testicular ischemia-reperfusion (I/R)
      injury in association with germ cell death, through either necrosis or apoptosis.
      Western blot analysis showed that iNOS expression was markedly increased 1 h
      after ischemia, and was accompanied by a huge nitric oxide (NO) production, as
      measured by the Griess method, with a peak at 48 h of reperfusion.
      Immunohistochemistry showed that iNOS was expressed predominantly in the
      macrophage-like cells infiltrated in the interstitial tissues of the testis.
      Intraperitoneal injection of aminoguanidine (AMG) (400 mg/day), the inhibitor of
      iNOS, reduced NO production by 57.7% at 96 h of reperfusion. Calpain activation
      and proteolysis of alpha-fodrin induced by I/R were inhibited by AMG. Germ cell
      apoptosis was demonstrated by in situ TUNEL and DNA fragmentation on agarose gel
      electrophoresis. Germ cell apoptosis was maximally induced at 24 h of
      reperfusion, and was not inhibited by AMG. NO produced by iNOS in the delayed
      phase of reperfusion promoted alpha-fodrin proteolysis, which is closely
      associated with necrosis. Inducible NOS inhibition combined with calpain
      inhibition may improve impaired spermatogenesis after testicular torsion.

PMID- 11466221
TI  - Delay in sexual maturity of the follicle-stimulating hormone receptor knockout
      male mouse.
AB  - In the highly organized and complex process of mammalian spermatogenesis, the
      development of an undifferentiated diploid germ cell into a fully differentiated
      and mature spermatozoon is orchestrated in a time frame unique for each species
      including man. If the various hormonal signals including environmental cues that
      play a critical part in initiating these events are not properly executed,
      various deficiencies including delay in sexual maturity or puberty are likely. In
      this study we have followed testicular development and spermatogenesis in the FSH
      receptor knockout (FORKO) mice from Day 7 onward by using histology and
      quantitative DNA flow cytometry. The drastic reduction in testicular weight and
      shrinkage of seminiferous tubules that occurred at this early age persisted into
      the adult stage in the FORKOs, suggesting inhibition of the initial developmental
      processes. The round spermatids that were clearly abundant on Day 21 in the wild
      type and heterozygous males were few and present only in some tubules of the
      FORKOs. There were no elongated spermatids in FORKO males on Day 35. The sperm
      produced by Day 49 FORKOs were already aberrant, a feature that persisted into
      adulthood in these animals. As all these changes occurred in a background of
      normal circulating testosterone levels, we may conclude that the delay in
      testicular development is a consequence of the loss of FSH-receptor signaling.
      The delay in sexual maturity of FORKOs was accompanied by reduction in fertility
      as evidenced by mating studies. Based on these data we suggest that the FORKO
      mouse might be a useful experimental model to define the molecular mechanisms
      that underlie the delay in puberty.

PMID- 11466222
TI  - Testosterone suppresses spermatogenesis in juvenile spermatogonial depletion (jsd
      ) mice.
AB  - Male juvenile spermatogonial depletion (jsd/jsd) mice are sterile because of a
      failure of spermatogonial differentiation. We have previously reported the
      recovery of spermatogonial differentiation by suppressing the levels of
      gonadotropins and testosterone with Nal-Glu, a GnRH antagonist. To determine
      whether suppression of testosterone or the gonadotropins was responsible for
      spermatogenic recovery, we examined the effect of supplementation of LH or FSH
      along with Nal-Glu treatment. Systemic administration of flutamide, an androgen
      receptor antagonist, was also examined. LH supplementation elevated both serum
      and intratesticular testosterone levels and suppressed the recovery of
      spermatogonial differentiation in a dose-dependent manner. Supplementation with
      FSH did not affect either testosterone levels or spermatogonial differentiation.
      Furthermore, the mice treated with flutamide showed some recovery of
      spermatogonial differentiation. The overall findings revealed that testosterone
      action mediated by androgen receptors suppressed the spermatogonial
      differentiation in jsd/jsd mice and suggested that spermatogonial differentiation
      in the jsd mutant is highly sensitive to testosterone suppression.

PMID- 11466223
TI  - Changes in the expression of tachykinin receptors in the rat uterus during the
      course of pregnancy.
AB  - In the mammalian female reproductive tract, tachykinin neuropeptides, such as
      substance P (SP), are localized to a population of sensory fibers and their
      precise physiological role is still unknown. The aim of the present study was to
      characterize the population of tachykinin receptors in the pregnant rat uterus
      and to assess their regulation during the course of pregnancy and after delivery.
      The expression of the tachykinin NK(1) receptor (NK(1)R), the tachykinin NK(2)
      receptor (NK(2)R), and the tachykinin NK(3) receptor (NK(3)R) in uteri from rats
      at different stages of pregnancy and on Day 1 postpartum was investigated by
      using a semiquantitative reverse transcription-polymerase chain reaction. The
      contractile effect of tachykinin receptor agonists acting selectively on the
      NK(1)R, the NK(2)R, or the NK(3)R was investigated by conventional organ bath
      techniques. Serum levels of estrogen and progesterone were measured by RIA. Our
      data show that the expression and function of NK(1)R and NK(3)R varied along the
      course of pregnancy and at postpartum. Uterine NK(2)R mRNA levels remain stable
      during the course of pregnancy and at Day 1 postpartum; and the contractions
      elicited by activating selectively the NK(2) receptor in the presence of the
      neutral endopeptidase inhibitor phosphoramidon (1 microM) were similar in early,
      mid, or late pregnancy. These results show that the expression and function of
      tachykinin receptors within the uterus vary with reproductive state and length of
      gestation, supporting a role for tachykinins in pregnancy and/or parturition in
      the rat.

PMID- 11466224
TI  - Spermatozoa of the shrew, Suncus murinus, undergo the acrosome reaction and then
      selectively kill cells in penetrating the cumulus oophorus.
AB  - In the musk shrew, Suncus murinus (and other shrews), the cumulus oophorus is
      ovulated as a discrete, compact, matrix-free ball of cells linked by specialized
      junctions. In examining how they penetrate the cumulus, Suncus spermatozoa were
      observed to first bind consistently by the ventral face over the acrosomal region
      to the exposed smooth surface of a peripheral cumulus cell. This was apparently
      followed by point fusions between the plasma and outer acrosomal membranes.
      Thereafter, spermatozoa without acrosomes were observed within cumulus cells that
      displayed signs of necrosis, as did some radially neighboring cumulus cells
      linked by zona adherens and gap junctions. Eventually, penetration of spermatozoa
      as far as the perizonal space around the zona pellucida left linear tracks of
      locally necrotic cells flanked by normal cumulus cells. Based on these and
      previous observations, we conclude that the acrosome reaction in Suncus is always
      induced by cumulus cells, and that reacted spermatozoa penetrate the cumulus by
      selective invasion and killing of cumulus cells along a linear track. Loss of the
      acrosome also exposes an apical body/perforatorium that is covered with barbs
      that appear to assist reacted fertilizing spermatozoa in binding to the zona
      pellucida. Because fertilized eggs displayed no other spermatozoa within or bound
      to the zona, an efficient block to polyspermy must prevent such binding of
      additional spermatozoa.

PMID- 11466225
TI  - Impaired maturation, fertilization, and embryonic development of porcine oocytes
      following exposure to an environmentally relevant organochlorine mixture.
AB  - The reproductive health risks related to exposure to persistent organic
      pollutants in the environment remain controversial. This debate is partly because
      most studies have investigated only one or two chemicals at a time, whereas
      populations are exposed to a large spectrum of persistent chemicals in their
      environment. Using the pig as a toxicological model, we hypothesized that
      exposing immature cumulus-oocyte complexes to an organochlorine mixture during in
      vitro maturation (IVM) would adversely affect oocyte maturation, fertilization,
      and subsequent embryo development. This organochlorine mixture mimics that which
      contaminates the Arctic marine food chain. Cumulus-oocyte complexes were cultured
      in IVM medium containing increasing concentrations of the organochlorine mixture,
      similar to that found in women of highly exposed populations. Organochlorines
      reduced the quality of cumulus expansion and the viability of cumulus cells in a
      dose-response manner. The proportion of apoptotic cumulus cells also increased
      due to organochlorine exposure. Half of the oocytes were fixed after
      insemination, and the remainders were cultured for 8 days. Concentrations of
      organochlorines did not affect the rates of oocyte degeneration, sperm
      penetration, and development to morula. However, incidence of incompletely
      matured oocytes increased and polyspermy rate decreased, both in a dose-response
      manner with increasing organochlorine concentrations. Blastocyst formation and
      number of cells per blastocyst declined with organochlorine concentration.
      Exposing porcine cumulus-oocyte complexes to an environmentally pertinent
      organochlorine mixture during IVM disturbs oocyte development, supporting recent
      concerns that such pollutants harm reproductive health in humans and other
      mammalian species.

PMID- 11466226
TI  - Cyclic adenosine 3',5'-monophosphate (cAMP) and cAMP responsive element-binding
      protein are involved in the transcriptional regulation of gonadotropin-releasing
      hormone (GnRH) receptor by GnRH and mitogen-activated protein kinase signal
      transduction pathway in GGH(3) cells.
AB  - Stimulation of mouse GnRH receptor promoter by a GnRH agonist (Buserelin), or by
      a cAMP analogue, significantly increased reporter (luciferase) activity.
      Overexpression of Raf-1, ERK1, or ERK2 partially blocked Buserelin-stimulated
      luciferase activity. In contrast, treatment with a mitogen-activated protein
      kinase (MAPK) kinase inhibitor (PD 98059) activated basal and Buserelin
      stimulated luciferase activity in a dose-dependent manner. Transient transfection
      of the deleted cAMP response element expression vector followed by pretreatment
      with PD98059 prior to Buserelin stimulation showed that the transcriptional
      response was decreased compared to wild-type promoter. A gel-mobility shift assay
      using a probe containing the cAMP response element showed the presence of two
      specific protein-DNA complexes that contain one or more members of the cAMP
      responsive element-binding (CREB) protein family. These results suggest that cAMP
      and CREB participate in the GnRH activation of GnRH receptor promoter activity
      and that the MAPK cascade is involved in the negative regulation of basal and
      GnRH-stimulated GnRH receptor transcriptional activity.

PMID- 11466227
TI  - Role of the transcriptional coactivator CBP/p300 in linking basic helix-loop
      helix and CREB responses for follicle-stimulating hormone-mediated activation of
      the transferrin promoter in Sertoli cells.
AB  - Sertoli cells are the epithelial cells responsible for the onset of pubertal
      development and the maintenance of spermatogenesis in the adult. Transferrin is
      one of the major secretory products expressed by differentiated Sertoli cells.
      Investigation of the transcriptional control of transferrin gene expression
      provides insight regarding the regulation of Sertoli cell differentiation. The
      optimal activation of the mouse transferrin promoter (mTf) by FSH requires the
      synergistic actions of the cAMP response element-binding protein (CREB) binding
      to the cAMP response element-like proximal region II (PRII) and the basic helix
      loop-helix (bHLH) binding to the E-box. Proximal region II alone is sufficient
      for cAMP-mediated activation. The proximity of the PRII and E-box (220 base pairs
      apart) suggests the possibility of interaction between CREB and bHLH proteins.
      Such an interaction can be mediated by transcriptional integrators such as CREB
      binding protein (CBP) and/or p300 and may stabilize the binding of trans-acting
      factors to their respective cis-elements. Such an interaction may also provide a
      mechanism for cell-specific promoter activation. The hypothesis tested in this
      study was that CBP/p300 is required for the synergistic activation of the
      transferrin promoter involving PRII and E-box through the formation of a ternary
      complex. In the Sertoli cells, both CBP and p300 proteins are expressed. The
      effect of CBP/p300 on transferrin promoter activation and, hence, Sertoli cell
      function was studied by using antisense oligonucleotides (AS-oligo). In the
      presence of CBP/p300 AS-oligo, activity of the FSH-induced mTf-chloramphenicol
      acetyl transferase (CAT) was significantly lower as compared to the respective
      controls. Interestingly, AS-oligo had no effect on cAMP-induced activation of the
      transferrin promoter reporter construct (mTf-CAT). Mutations in the E-box (EB*)
      significantly reduced the FSH response. The presence of AS-oligo had no further
      effect on the FSH-mediated activation of the EB*-mTf-CAT construct but reduced
      cAMP-mediated activation. Mutations in the CRE-like PRII (PRII*) also
      significantly reduced the FSH response. Activation of the PRII*-mTf-CAT in
      response to cAMP was completely abolished. The presence of AS-oligo had no
      further effect on the FSH- or cAMP-mediated activation of the PRII*-mTf-CAT
      construct. In Sertoli cells, CBP/p300 was coimmunoprecipitated with CREB and the
      bHLH protein E47. These observations suggest that CBP/p300 appears to be involved
      in regulating FSH-mediated activation of the transferrin promoter by linking bHLH
      and CREB activities.

PMID- 11466228
TI  - Epididymal specificity and androgen regulation of rat EP2.
AB  - In primates, expression of the EP2 gene is androgen-dependent and epididymis
      specific. EP2 mRNA expression was investigated in caput, corpus, and cauda
      regions of rat epididymis and in 15 other rat tissues. Polymerase chain reaction
      and Northern analyses showed that rat EP2 is expressed predominantly in the
      proximal caput epididymidis. EP2 mRNA expression was determined in proximal
      epididymides from castrated, sham-operated, and efferent duct-ligated rats. In
      castrated rats, EP2 mRNA decreased to <10% of that in sham-operated rats between
      Days 3 and 4 postcastration, demonstrating the androgen dependence of EP2
      expression. In epididymides ligated unilaterally at the efferent ducts, EP2 mRNA
      levels were approximately equal to those in the unligated contralateral
      epididymides or in sham-operated rats, indicating that EP2 expression does not
      depend on testicular factors. In bilaterally castrated rats, immediate and
      delayed testosterone replacement showed the dependence of EP2 expression on
      circulating androgens. Injection of testosterone propionate (TP) on Days 0, 1, 2,
      and 3 postcastration maintained EP2 mRNA levels approximately equal to those in
      sham-operated rats. Starting at Day 4 postcastration, daily injection of TP for 7
      days restored EP2 mRNA to approximately normal levels. These data indicate for
      the rat that EP2 is expressed specifically in the proximal caput epididymidis and
      that its expression depends on circulating androgens but not on testicular
      factors.

PMID- 11466229
TI  - Alteration of activation, growth, and atresia of bovine preantral follicles by
      long-term treatment of cows with estradiol and recombinant bovine somatotropin.
AB  - The hypothesis was that long-term treatment of cattle with estradiol (E(2)) and
      bovine somatotropin (bST) would alter the earliest stages of folliculogenesis.
      Nonlactating Holstein cows (n = 26) were treated in a 2 x 2 arrangement with E(2)
      (2 x 24 mg implants, 67.1 +/- 1.4 days) and bST (Posilac, 63.6 +/- 1.5 days). At
      Day 67 +/- 1.3, one ovary was removed for morphometric and immunohistochemical
      analysis. For each ovary, 388 +/- 38 microscopic fields (2 x 2 mm) were examined
      and follicles within each field were classified by histological stage. Fields
      that contained no follicles were classified as empty. Empty fields (n = 100 per
      ovary) were further classified as containing no evidence of follicles or
      containing atretic remnants of follicles. Approximately 30 4-microm sections per
      ovary were stained for proliferating cell nuclear antigen (PCNA), and 150 fields
      per ovary were evaluated. Additional sections (n = 10 per ovary) were assessed
      immunohistochemically for apoptosis, and fluorescence intensity was determined
      for each follicle. Treatment with bST significantly decreased percentage of empty
      fields containing atretic remnants. Treatment with E(2) induced activation of
      follicles as shown by a decrease in percentage of primordial follicles and an
      increase in percentage of primary follicles as determined by PCNA staining. At
      the primary follicle stage the combination of bST + E(2) decreased apoptosis as
      shown by decreased fluorescence intensity. Thus, E(2) induced activation of
      follicles, bST enhanced survival, and the combination lowered atresia.

PMID- 11466230
TI  - Polyamine- and insulin-like growth factor-I-mediated proliferation of porcine
      uterine endometrial cells: a potential role for spermidine/spermine N(1)
      acetyltransferase during peri-implantation.
AB  - Insulin-like growth factor-I (IGF-I) and the polyamine catabolic enzyme
      spermidine/spermine N(1)-acetyltransferase (SSAT) are progesterone-regulated
      genes with maximal expression at peri-implantation in the porcine uterine
      endometrium. However, while IGF-I stimulates cell proliferation, SSAT, by
      acetylating the naturally occurring polyamines (PA) spermine (SPM) and spermidine
      (SPD), typically functions as a cell growth inhibitor. The present study examined
      the functional relationships of IGF-I, SSAT, and PA in the control of endometrial
      cell proliferation. Northern blot analysis indicated that SSAT mRNA levels change
      with distinct pregnancy stages, in contrast to those for the PA biosynthetic
      enzyme ornithine decarboxylase (ODC). Primary cultures of luminal and glandular
      epithelial (LE, GE) and stromal (ST) cells isolated from Day 12 pregnant pig
      endometrium had IGF-I mRNA levels for ST > LE > GE cells. The mRNA levels for
      SSAT and ODC were transiently diminished by IGF-I treatment, but only in GE
      cells. By contrast, SPM and SPD increased SSAT mRNA levels in GE and ST cells,
      but increased ODC mRNA levels only in GE cells. IGF-I, putrescine (PUT), and SPM
      individually increased cellular DNA synthesis as measured by tritiated thymidine
      incorporation in GE and ST cells, while SPD had an effect only in ST cells. IGF-I
      enhanced the proliferative effect of each PA in GE cells, but only of SPD in ST
      cells. The mitogen-activated protein kinase inhibitor, PD98059, inhibited the
      induction by SPM of GE cell DNA synthesis but not that of IGF-I. Wortmannin, a
      phosphatidylinositol-3-kinase inhibitor had no effect on either IGF-I or SPM
      induction of GE cell DNA synthesis. The relative concentrations of SPM, SPD, and
      PUT in uterine luminal fluids differed, with the levels for each PA higher at
      pregnancy Day 12 than at 11.5. These results suggest that IGF-I and PA act
      through distinct signaling pathways to mediate cell-type-specific growth of early
      pregnancy pig uterine endometrium. Further, SSAT, through its control of
      intracellular PA levels, likely plays a modulatory role in the establishment of
      an optimal uterine environment for successful embryo attachment.

PMID- 11466231
TI  - Natriuretic peptides stimulate steroidogenesis in the fetal rat testis.
AB  - To study the regulation of fetal testicular steroidogenesis in the rat, we
      examined effects of members of the natriuretic peptide family, that is, atrial
      natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type
      natriuretic peptide (CNP), on testosterone production of dispersed Leydig cells
      of rat fetuses at Embryonic Day (E) 18.5. All three peptides stimulated
      testosterone production, with significant effect at concentrations > or =1 x 10(
      8) mol/L of ANP, > or =1 x 10(-9) mol/L of BNP, and > or =1 x 10(-6) mol/L of
      CNP. Likewise, receptors for all three peptides (i.e., NPR-A, NPR-B, and NPR-C)
      were expressed in the fetal testis as early as E15.5. The natriuretic peptides
      had no effect on cAMP production by fetal Leydig cells. When tested in
      combination with two other peptides previously shown to stimulate fetal
      testicular steroidogenesis, vasoactive intestinal peptide and pituitary adenylate
      cyclase-stimulating polypeptide (PACAP-27), the combined effects did not differ
      significantly from the maximum effect with any one of the peptides alone. In
      conclusion, our present findings provide both functional and molecular evidences
      for NPR-A, NPR-B, and NPR-C in the fetal testis. Because ANP has previously been
      detected in fetal plasma and we now demonstrate the expression of BNP and CNP in
      fetal testes, these findings indicate involvement of the natriuretic peptides in
      endocrine and paracrine regulation during the early phase of fetal testicular
      steroidogenesis at E15.5--19.5 (i.e., before the onset of pituitary LH
      secretion).

PMID- 11466232
TI  - Expression, activity, and subcellular localization of testicular hormone
      sensitive lipase during postnatal development in the guinea pig.
AB  - The present work reports on testicular hormone-sensitive lipase (HSL), the
      biological significance of which has been documented in male fertility. The HSL
      protein levels and enzymatic activity were measured, respectively, by
      densitometry of immunoreactive bands in Western blots, performed with antibodies
      against recombinant rat HSL, and by spectrophotometry in seminiferous tubules
      (STf) and interstitial tissue (ITf) enriched fractions generated from neonatal,
      pubertal, and adult guinea pig testes. In addition, HSL was studied in
      subcellular fractions obtained from STf isolated from adult testes and in
      epididymal spermatozoa (Spz). A 104-kDa HSL protein was detected in STf and ITf,
      the expression and activity of which increased with testicular development. Three
      immunoreactive bands of 104, 110, and 120 kDa were detected in the lysosomal
      subfraction, and two bands of 104 and 120 kDa were detected in Spz. The HSL
      activity was positively correlated with free (FC) and esterified (EC) cholesterol
      ratios in STf and ITf, but not with triglyceride (TG) levels, during testicular
      development. Immunolabeling localized HSL to elongated spermatids and Sertoli
      cells, where its distribution was stage-dependent, and within the cells lining
      the excurrent ducts of the testis. The findings of the 104- and 120-kDa HSL
      immunoreactive bands and of HSL activity in Spz as well, as the detection of the
      104-, 110-, and 120-kDa immunoreactive bands in lysosomes, suggest that part of
      HSL may originate from germ cells and be imported in Sertoli cells. The HSL
      protein levels and enzymatic activity in ITf and STf were positively correlated
      with serum testosterone levels during development. To the best of our knowledge,
      this study is the first to contribute insights regarding the impact of HSL on
      FC:EC cholesterol ratios and TG levels in the interstitial tissue and tubules in
      relation to serum testosterone levels during postnatal development, and regarding
      the immunolocalization of the enzyme in regions of the male gamete consistent
      with spermatozoa-oocyte interaction.

PMID- 11466233
TI  - Estrogen-induced gonadal sex reversal in the tammar wallaby.
AB  - Estrogens have a feminizing effect on gonadal differentiation in fish,
      amphibians, reptiles, and birds. However, the role of estrogen during gonadal
      differentiation in mammals is less clear. We investigated the effect of estrogen
      on gonadal differentiation of male tammar wallabies. Male pouch young were
      treated orally with estradiol benzoate or oil from the day of birth, before
      seminiferous cords develop, to Day 25 postpartum and were killed at Day 50
      postpartum. In all estrogen-treated neonates, a decrease in gonadal volume,
      volume of the seminiferous cords, thickness of the tunica albuginea, and number
      of germ cells was found. The stage of treatment affected the magnitude of the
      response. Two of three male young born prematurely after 25 days of gestation and
      treated subsequently with estradiol had ovary-like gonads, with well-developed
      cortical and medullary regions and primordial follicle formation. Furthermore, at
      Day 50 postpartum, many (21%) of the germ cells in these sex-reversed ovaries
      were in the leptotene and zygotene stages of meiosis, similar to female germ
      cells at the same stage of development. In the other males born on Day 26 of
      gestation or later, estradiol treatment from the day of birth caused development
      of dysgenetic testes, with abnormal Sertoli cells, atrophy of the seminiferous
      tubules and tunica albuginea, and absence of meiotic germ cells. In this
      marsupial, therefore, estradiol can induce either partial or complete
      transformation of the male gonads into an ovary with meiotic germ cells. These
      results confirm that estrogen can inhibit early testicular development, and that
      testis determination occurs during a narrow window of time.

PMID- 11466234
TI  - 2-Methoxyestradiol, an endogenous estradiol metabolite, differentially inhibits
      granulosa and endothelial cell mitosis: a potential follicular antiangiogenic
      regulator.
AB  - 2-Methoxyestradiol (2-ME) is an estradiol metabolite with antiangiogenic and
      antitumor activity. It is formed by granulosa cell (GC) catechol-O
      methyltransferase activity and is present in the normal follicle at high
      concentrations. In this unique microenvironment, it may regulate selected cell
      types via autocrine and/or paracrine action. To assess the possibility that 2-ME
      or estradiol might exert differential mitotic and/or apoptotic effects on
      endothelial cells and GCs, we compared their actions on primary cultures of
      hormone- and/or growth factor-stimulated porcine GCs (pGCs) as well as two types
      of endothelial cells, primary cultures of porcine endothelial cells (pECs), and a
      spontaneously transformed rabbit endothelial vascular cell (REVC) line. The 2-ME,
      but not estradiol, dose dependently suppressed tritiated thymidine ((3)H-T)
      incorporation into epidermal growth factor (EGF)-stimulated REVCs and EGF/insulin
      (INS)-stimulated pECs. In contrast, 2-ME did not attenuate incorporation in
      FSH/INS-stimulated pGCs. It reduced incorporation by approximately 50% in EGF/INS
      stimulated pGCs, indicating that responsiveness to 2-ME in normal cells can be
      modulated by hormone and growth factor treatment. Estradiol was not antimitotic
      to pGCs. As indicated by 4',6-diamido-2-phenylindole hydrochloride nuclear
      staining, estradiol was nonapoptotic in either cell type, and 2-ME significantly
      increased apoptosis of REVCs, but not of pGCs. In a cell migration assay, REVC
      movement was attenuated by 2-ME, but not by estradiol. In summary, the results
      show that antimitotic as well as proapoptotic responses to 2-ME vary with cell
      type and, in the case of pGC antimitotic activity, with the regulatory
      microenvironment. Thus, they provide a rationale for autocrine and/or paracrine
      action of 2-ME at its site of production in vivo, and they strongly support the
      concept of 2-ME as a candidate ovarian angiogenesis inhibitor.

PMID- 11466235
TI  - Characterization of an 80-kilodalton bull sperm protein identified as PH-20.
AB  - This paper presents the partial characterization and the identification of an 80
      kDa protein detected in bull spermatozoa using a monoclonal antibody directed
      against a 16-amino acid long peptide from the N-terminal domain of the
      protooncogene p60(src) from the Rous Sarcoma Virus When subjected to two
      dimensional electrophoresis, this 80-kDa protein migrated as several isoforms,
      with an isoelectric point ranging from 7.4 to 8.2. Amino acid sequence analysis
      of a peptide obtained following trypsin digestion of the bull sperm protein
      showed homology to the PH-20/hyaluronidase precursor sperm protein. As for PH-20,
      this bull sperm 80-kDa protein is located at the plasma membrane surface in the
      postacrosomal region of the head. An increased immunolabeling in the anterior
      head region of fixed/permeabilized spermatozoa was observed when these cells were
      incubated under capacitating conditions, whereas most sperm cells challenged with
      the calcium ionophore A23187 to acrosome react lost their labeling almost
      completely. As for the PH-20 protein, the 80-kDa bull sperm protein possesses a
      hyaluronidase activity that is higher at pH 7.0 than at pH 4.0 in an in-gel
      assay. Unlike what has been observed in the guinea pig, mouse, and human PH-20,
      this 80-kDa protein was not released from the surface of bull spermatozoa by
      treatment with phosphatidylinositol-specific phospholipase C or with trypsin.
      However, this protein was not sedimented by a 100,000 x g centrifugation after
      nitrogen cavitation, which suggests that the 80-kDa protein is loosely attached
      to the sperm membrane by a yet-unknown mechanism. These results suggest that the
      80-kDa bull sperm protein shares many homologies with the sperm PH-20 protein
      reported in the literature and, most likely, is the bull sperm homologue of the
      PH-20.

PMID- 11466236
TI  - Gene therapy for retinopathy of prematurity: the eye is a window to the future.

PMID- 11466237
TI  - Optic disc changes following trabeculectomy.

PMID- 11466239
TI  - "Don't worry my good man--you won't understand our medical talk": consent to
      treatment today.

PMID- 11466241
TI  - Amniotic membrane grafts, "fresh" or frozen? A clinical and in vitro comparison.
AB  - BACKGROUND/AIMS: The use of "fresh" (hypothermically stored) and frozen amniotic
      membrane (AM) was compared in a patient with cicatricial pemphigoid with stem
      cell failure. The viability of both "fresh" and frozen AM epithelial cells was
      assessed after storage. METHODS: AM was stored at either +4 degrees C ("fresh")
      or at -80 degrees C (frozen). A "fresh" graft was applied to the cornea following
      superficial keratectomy. Subsequently, a further frozen graft was applied to the
      same eye. Viability of the stored AM epithelium was assessed by investigating
      membrane integrity and mitochondrial activity. RESULTS: In both cases the cornea
      re-epithelialised and visual acuity improved. Improvement, however, was not
      sustained. CONCLUSION: Although both procedures led to an improvement in visual
      acuity, "fresh" tissue performed no better than frozen in promoting re
      epithelialisation. The authors suggest that logistical, safety, and cost
      considerations outweigh any benefits of using "fresh" as opposed to frozen graft
      material.

PMID- 11466240
TI  - Blindness in Africa: present situation and future needs.
AB  - AIM: To review the prevalence and causes of blindness in sub-Saharan Africa, the
      existing services and limitations, and the Vision 2020 goals for the future.
      METHODS: Methodologically sound population based surveys published in the past 20
      years are reviewed and results for prevalence and causes of blindness are
      tabulated. The current resources and needs according to recent publications and
      international working groups are described. CONCLUSIONS: Blindness prevalence
      rates vary widely but the evidence suggests that approximately 1% of Africans are
      blind. The major cause is cataract; trachoma and glaucoma are also important
      causes of blindness. The bulk of blindness in the region is preventable or
      curable. Efforts should focus on eye problems which are universally present and
      for which there are cost effective remedies, such as cataract and refractive
      problems and on those problems which occur focally and can be prevented by
      primary healthcare measures, such as trachoma, onchocerciasis, and vitamin A
      deficiency. Major development of staffing levels, infrastructure, and community
      programmes will be necessary to achieve Vision 2020 goals.

PMID- 11466242
TI  - Combined phototherapeutic keratectomy and therapeutic contact lens for recurrent
      erosions in bullous keratopathy.
AB  - AIMS: To evaluate the therapeutic effects of excimer laser phototherapeutic
      keratectomy (PTK) combined with therapeutic contact lens for painful recurrent
      corneal erosions (RCE) secondary to bullous keratopathy (BK) not suitable for
      penetrating keratoplasty. METHODS: Excimer laser PTK was performed prospectively
      in eight eyes with painful RCE due to BK visually expecting no benefit from
      penetrating keratoplasty. After mechanical removal of the epithelium, the corneas
      were ablated with 50 pulses in the central 6.5 mm zone (ablation rate 0.25 microm
      per pulse) and another 200 pulses for polishing the periphery. After PTK,
      therapeutic contact lenses were applied for 3 months. The mean follow up period
      after PTK was 10.9 months (ranging from 6 to 15 months). RESULTS: All patients
      experienced relief of their pain symptoms after the epithelium healed. Only one
      patient complained of occasional stinging pain with intermittent recurrence of
      small bullae. He refused a second treatment because the pain was much less than
      that before the surgery and quite tolerable. No infection or other complications
      were noted. CONCLUSION: PTK with deeper ablation and adjunctive therapeutic
      contact lens is an easy to perform and effective treatment with less recurrence
      rate for patients with BK and poor visual potential.

PMID- 11466243
TI  - A comparison of different depth ablations in the treatment of painful bullous
      keratopathy with phototherapeutic keratectomy.
AB  - AIM: To study the efficacy of phototherapeutic keratectomy (PTK) for pain relief
      for patients with painful bullous keratopathy and poor visual potential. METHODS:
      Patients with painful bullous keratopathy and poor visual potential were treated
      with superficial PTK (8-25 microm), intermediate (50-100 microm) or deep PTK (25%
      stromal thickness) using the Nidek EC5000 excimer laser after manual epithelial
      debridement. Follow up ranged from 1 to 24 months (mean 6.5 months). Outcome
      measures included symptomatic relief and need for further treatment. RESULTS: In
      the superficial PTK group five of eight (62%) patients improved symptomatically
      after treatment. The three (38%) who did not improve went on to have penetrating
      keratoplasty for pain relief. In the intermediate depth group only two of five
      (40%) patients had symptom alleviation. The three others (60%) required further
      procedures. 20 of 24 (83%) patients treated with deep PTK had significant or
      total alleviation of symptoms. Of these, one developed acute anterior uveitis 9
      months after PTK and two required botulinum ptosis for persistent corneal
      epithelial defects, one of whom had three consecutive episodes of microbial
      keratitis. Three of 24 suffered occasional discomfort and one patient required a
      penetrating keratoplasty for continued pain. CONCLUSION: PTK can be a useful
      therapeutic measure in painful bullous keratopathy with poor visual potential.
      Deep PTK appears to be more successful in pain management than superficial
      treatment.

PMID- 11466244
TI  - The cornea in young myopic adults.
AB  - AIMS: To further understand the effect of refractive error on the corneal
      dimensions and function. METHODS: Corneal curvature, corneal thickness, and axial
      length measurements were performed, as well as specular microscopy and
      fluorophotometry, on patients with various refractive statuses. 216 subjects,
      mean age 22.2 (SD 4.2) years, were examined. Patients with previous contact lens
      wear history, external eye diseases, as well as previous ocular surgeries, were
      excluded. RESULTS: The corneas were flatter in eyes with longer axial length (r =
      -0.22, p = 0.003). Eyes with more myopic spherical equivalent had longer axial
      length (r = -0.90, p <0.001) as well as less corneal endothelial density (r =
      0.20, p = 0.037). Corneal endothelial density decreased in eyes with longer axial
      length (r = 0.24, p = 0.019); however, it correlated neither with corneal
      thickness (r = -0.06, p = 0.59) nor with corneal curvature (r = -0.07, p = 0.52).
      The corneas had a mean corneal thickness of 533 (SD 29) microm and were thinner
      in more myopic eyes (r = 0.16, p = 0.021). The corneas tended to be thinner in
      eyes with longer axial length. However, the correlation did not reach statistical
      significance (r = -0.11, p = 0.14). Besides, there was no significant correlation
      between the corneal thickness and the corneal curvature (r = -0.13, p = 0.093)
      and the endothelial permeability (r = 0.042, p = 0.69). The corneas with higher
      endothelial density had larger corneal transfer coefficient (r = 0.26, p = 0.024)
      and higher permeability to fluorescein molecules (r = 0.28, p = 0.014).
      Nevertheless, the corneal endothelial permeability did not correlate
      significantly with either the axial length (r = -0.18, p = 0.11) or the degree of
      myopia (r = 0.12, p = 0.26). CONCLUSION: Changes in the anterior segments as the
      eyeball elongates in myopia progression included flatter corneal curvature,
      decreased corneal thickness, as well as decreased endothelial density. These
      factors should be considered in refractive surgery.

PMID- 11466245
TI  - Ocular hypotensive efficacy and safety of once daily carteolol alginate.
AB  - BACKGROUND/AIM: Carteolol is a beta adrenoceptor antagonist used topically to
      reduce intraocular pressure, typically twice daily. In an effort to provide a
      once daily dosing regimen, carteolol was formulated with 1% alginic acid. The
      objective of this study was to evaluate the efficacy and safety of carteolol
      alginate solution in comparison with standard carteolol solution. METHODS: This
      was a double masked, parallel group, multicentre study. Patients with ocular
      hypertension or open angle glaucoma (n=235) were randomly assigned to receive
      either carteolol alginate once daily [corrected] or standard carteolol solution,
      twice daily. The masking was maintained through the use of a vehicle in the
      evening for the alginate group. Patients were evaluated at baseline, 15, 60, and
      120 days. RESULTS: At 0900 (presumed trough) on day 60, mean reductions in
      intraocular pressure (IOP) from baseline were 6.09 (SD 2.97) and 6.09 (3.18) mm
      Hg for the standard carteolol and alginate, respectively. At 1100 (presumed
      peak), mean reductions were 6.51 (2.53) and 6.47 (2.76) mm Hg, respectively.
      Results were similar at other times (day 15 and day 120). The most common side
      effect was transient stinging on instillation of drops, which did not differ
      significantly between groups. There were no differences of note in other ocular
      or systemic signs or symptoms. CONCLUSION: The new alginate formulation of
      carteolol 2% given once daily was as effective as standard carteolol 2% given
      twice daily with no meaningful differences regarding safety.

PMID- 11466246
TI  - Is the pulse rate useful in assessing risk of diabetic retinopathy and macular
      oedema? The Wisconsin Epidemiological Study of Diabetic Retinopathy.
AB  - AIM: To describe the relation between pulse rate and incident diabetic
      retinopathy. METHODS: Population based cohort study of people with diabetes.
      Resting pulse rate was measured in 30 second intervals. Diabetic retinopathy was
      evaluated from masked gradings of fundus photographs. RESULTS: People with higher
      pulse rates were more likely to have 4 year progression of retinopathy,
      progression to proliferative retinopathy, and incident macular oedema than those
      with lower pulse rates. However, these associations were attenuated after
      controlling for blood pressure, glycosylated haemoglobin, and other risk factors.
      CONCLUSION: Pulse rate may be a clinical indicator of overall risk of diabetic
      retinopathy, but is not independently associated with the condition.

PMID- 11466247
TI  - Electrophysiological changes after 360 degrees retinotomy and macular
      translocation for subfoveal choroidal neovascularisation in age related macular
      degeneration.
AB  - AIM: To evaluate electrophysiological changes after 360 degrees retinotomy and
      macular translocation for subfoveal choroidal neovascularisation in patients with
      age related macular degeneration (AMD). METHODS: A consecutive series of 32
      patients suffering from subfoveal choroidal neovascularisation secondary to AMD
      underwent 360 degrees retinotomy and macular translocation. The ERG served as the
      main parameter of the study and was recorded 1 day before the translocation
      surgery and no earlier than 4 weeks after the silicone oil removal. RESULTS: The
      scotopic ERG amplitudes were significantly reduced after translocation surgery.
      Depending on the applied flash luminance the mean b-wave amplitude reduction of
      the scotopic ERG varied between 67% (0.2 cd.s/m2) and 74% (0.03 cd.s/m2). The a
      waves and b-waves of the saturating light response decreased significantly by 46%
      and 59%, respectively. The photopic a-wave and b-wave amplitudes were
      significantly lower after the translocation surgery resulting in a mean reduction
      of 27% and 43%, respectively. CONCLUSIONS: Although macular translocation may
      provide the potential of preserving and even restoring vision in patients with
      subfoveal choroidal neovascular membranes secondary to AMD the present study
      indicates that a significant electrophysiological decrease is caused by surgical
      procedures associated with this technique. Further research is necessary to
      clarify if certain modifications of the surgical procedure are able to
      substantially reduce the neuroretinal trauma.

PMID- 11466248
TI  - Reduced incidence of retinopathy of prematurity.
AB  - AIM: To audit the prevalence of retinopathy of prematurity (ROP) in a level 2
      status neonatal unit. METHODS: Data were collected prospectively over 9 years
      from September 1989 to September 1998. Preterm infants were examined according to
      the Royal College of Ophthalmologists' guidelines and retinopathy graded
      following the International Classification of ROP. ROP 3-5 was analysed using
      logistic regression in relation to time, and to gestational age and birth weight.
      RESULTS: 383 babies were examined. Mean gestational age fell over the 9 year
      period (p=0.051) as did mean birth weight (p<0.001). There was a decrease in the
      number of infants with ROP grades 3-5 over the 9 years (p=0.045 and, when
      adjusted for gestational age and birth weight, the decrease in ROP 3-5 was
      significant (p=0.03). CONCLUSIONS: This study found a significant reduction in
      the incidence of ROP during the 9 years of the study period, despite a decrease
      in mean gestational age of and birth weight. The reduced incidence of ROP is
      attributed to improvements in ventilation techniques and overall care of the
      neonate, in particular the use of prenatal steroids and surfactant.

PMID- 11466249
TI  - Outcome of cataract surgery in patients with retinitis pigmentosa.
AB  - AIM: To determine the visual benefit of cataract extraction in patients with
      retinitis pigmentosa and to identify risk factors for poor outcome. METHODS: A
      retrospective analysis was undertaken of a continuous series of 142 eyes of 89
      patients with retinitis pigmentosa undergoing cataract surgery between 1985 and
      1997. RESULTS: Mean age at surgery was 47.5 years (range 24-81 years). In 100
      eyes there was posterior subcapsular lens opacity alone, 37 eyes also had
      moderate nuclear sclerosis, and five had only nuclear sclerosis. All patients had
      central visual fields of <10 degrees. Overall, mean visual acuity improved from
      1.05 (SD 0.38) preoperatively to 0.63 (SD 0.49) postoperatively on the logMAR
      scale. Significant postoperative capsular opacification occurred in 88/139 eyes
      (63%) and 45.1% required capsulotomy. Anterior capsulotomy was undertaken in 5/52
      (9.6%) eyes undergoing phacoemulsification. Postoperative macular oedema was
      noted in 20 (14%) eyes. Visual acuity improved in 109 eyes (77%), was unchanged
      in 29 eyes (20.5%), and worsened after surgery in four eyes (2.5%). 86/89
      patients reported major improvement of visual function. CONCLUSIONS: Cataract
      surgery for relatively minor lens opacities is beneficial in patients with
      retinitis pigmentosa, and most report subjective improvement of visual symptoms.
      The incidence of capsular opacification is high and anterior capsular contraction
      may occur. The number of eyes with poor vision due to macular oedema was
      unexpectedly low.

PMID- 11466250
TI  - Accuracy of intraocular lens power calculation in paediatric cataract surgery.
AB  - AIMS: To determine the accuracy of intraocular lens (IOL) power calculation in a
      group of pseudophakic children. METHODS: A retrospective analysis of biometric
      and refractive data was performed on 52 eyes of 40 infants and children, who
      successfully underwent cataract extraction and IOL implantation. The following
      parameters were included: age at the time of surgery, keratometry, axial length,
      estimated refraction, and the power of IOL implanted. The postoperative
      refractive outcome was taken as the spherical equivalent of the refraction at 3
      months after surgery. The prediction error was taken as the absolute difference
      between the estimated and actual postoperative refraction. The data were analysed
      to assess the effects of age at the time of surgery, keratometry, and axial
      length on the accuracy of calculation of IOL power. RESULTS: For the overall
      group the mean and median prediction errors were 1.40 D and 0.84 D (SD 1.60). The
      mean and median prediction errors in eyes with axial lengths > or =20 mm were
      1.07 D and 0.71 D (SD 0.98) and in eyes <20 mm were 2.63 D and 2.61 D (SD 2.65).
      The mean and median prediction errors in eyes in children aged > or =36 months
      were 1.06 D and 0.68 D (SD 1.02) and in children aged <36 months was 2.56 D and
      2.29 D (SD 2.50). The differences between the prediction errors for both axial
      length and age were statistically significant (p<0.05). CONCLUSIONS: For the
      overall group IOL power calculation is satisfactory. In eyes with axial lengths
      less than 20 mm and in children less than 36 months of age larger errors can
      arise. This study demonstrates the need for an IOL formula specifically designed
      for paediatric use.

PMID- 11466251
TI  - Combined phacoemulsification and transpupillary drainage of silicone oil: results
      and complications.
AB  - AIM: To review retrospectively 74 consecutive cases of combined
      phacoemulsification and transpupillary drainage of silicone oil. METHODS:
      Candidate patients for intraocular silicone oil removal and cataract extraction
      underwent combined phacoemulsification and transpupillary drainage of silicone
      oil through a planned posterior capsulorrhexis and without the use of a pars
      plana infusion line. RESULTS: The retina remained attached in 59 (79.7%) patients
      postoperatively. In this success group, the postoperative visual acuity improved
      in 42 (71.2%) patients. There was no association between age, duration of
      silicone oil tamponade, preoperative diagnosis, macular status or number and
      nature of previous surgery, and the incidence of redetachment following silicone
      oil removal. CONCLUSION: Combined phacoemulsification and transpupillary drainage
      of silicone oil is a safe and reliable technique that offers the main advantage
      of diminished surgical trauma.

PMID- 11466252
TI  - The suitability of the ultrasound biomicroscope for establishing texture in giant
      cell arteritis.
AB  - AIM: To establish whether ultrasound biomicroscope (UBM) is a helpful tool in
      locating the arterial segment responsible in patients with segmental attacks in
      giant cell arteritis METHODS: The superficial temporal arteries of 19 patients
      with suspected giant cell arteritis were examined with the UBM before biopsy.
      RESULTS: 20 specimens provided the histological proof of giant cell arteritis in
      five patients. Side differences, a dark perivascular halo, and high reflexivity
      of the intra-arterial space were found. CONCLUSION: it is assumed that there are
      two types of arteritic inflammation: (1) the occlusion of intra-arterial space
      due to intimal fibrosis (UBM: high reflexive "filling"), and (2) inflammation of
      the perivascular zone with oedematous thickening and infiltration of the media
      (UBM: dark halo) and its combination. UBM is helpful in obtaining an indication
      of the side and segment for biopsy.

PMID- 11466253
TI  - Palisaded encapsulated neuroma (solitary circumscribed neuroma of skin) of the
      eyelid: report of two cases and review of the literature.
AB  - BACKGROUND/AIMS: Palisaded encapsulated neuroma of the skin (PEN) is an uncommon
      benign neural tumour that occurs on the head and neck, including the eyelid, but
      is unfamiliar to many ophthalmic clinicians. For the first time in the ophthalmic
      literature, the clinical and histopathological features of two patients with PEN
      of the eyelid are described. METHODS: Two cases of PEN were identified in the
      archives of the Department of Pathology, Institute of Ophthalmology, London.
      Clinical details were derived by a case note review and the histopathological
      features defined using standard methods including immunohistochemistry. RESULTS:
      Two cases of PEN are described, from the eyelids of patients aged 43 and 70
      years. The tumours were virtually identical in nature, being painless solid
      masses composed of a mixture of S100 positive Schwann cells and scattered
      neurofilament positive nerve fibres. An incomplete thin fibrous capsule, which
      contains EMA positive perineural cells, partially surrounded each lesion. The
      lesions were distinguishable from other more common eyelid lesions only on
      histopathological examination. Both tumours were completely excised with no
      evidence of recurrence. Neither patient had signs of any associated systemic
      disease. CONCLUSION: PENs are usually solitary, firm, non-pigmented, dome-shaped
      lesions that are found on the face of patients usually over the age of 40 years.
      Most often these lesions are diagnosed clinically as basal cell carcinomas,
      dermal naevi, or skin adnexal tumours. Histologically, PENs must be
      differentiated from other neural tumours that may be associated with systemic
      syndromes, such as neurofibromas or mucosal neuromas.

PMID- 11466254
TI  - The use of a newspaper insertion to promote DIY testing of vision in India.
AB  - BACKGROUND: The mass media have the potential to motivate people to participate
      in self appraisal of their own health status. An innovative communication package
      was designed to help people to examine vision at home. The impact of publishing
      the "do it yourself" (DIY) kit in Indian newspapers was evaluated. METHODS: A
      pretested bilingual vision testing kit was published in three newspapers. The kit
      comprised four tumbling Es corresponding to 6/12 line of Snellen's optotypes.
      Directions on using the kit were enclosed. 3 -7 days after publication of the
      kit, a telephone survey of newspaper readers was undertaken to evaluate the
      impact and cost effectiveness. RESULTS: 603 people were contacted over the
      telephone. 125 (20.73%) subscribed to the newspaper carrying the DIY insertion.
      43.2% (54) noticed the insertion of which 88.89% (48) read the enclosed
      instructions carefully. 58.33% respondents felt sufficiently motivated to contact
      an ophthalmologist. Graduates had a 3.83 times higher probability of reading the
      communication insertion compared with others. Differences in relation to other
      demographic variables were not statistically significant. CONCLUSIONS: Newspapers
      are an excellent medium for communicating self appraisal kits for vision testing.
      The medium is cost effective and has significant reach in the urban agglomerates
      of India.

PMID- 11466255
TI  - Optic disc changes following trabeculectomy: longitudinal and localisation of
      change.
AB  - AIMS: To determine whether there were any changes in the optic disc at 2 years
      after trabeculectomy. To determine the factors that most influenced change and
      whether change was localised to any region of the optic disc. METHODS: 95
      patients undergoing routine trabeculectomy as part of the ongoing Moorfields/MRC
      5-fluorouracil trial were recruited into the study. Eyes were imaged
      preoperatively (4 (SD 3) weeks) with the Heidelberg retina tomograph (HRT,
      Heidelberg Engineering), and at 3 months (SD 2 weeks), 1 year (SD 1 month), and 2
      years (SD 1 month) after surgery. Parameters investigated for change were rim
      area, rim volume, and maximum cup depth. The predefined segment analysis
      available on the HRT analysis software was used to determine segmental change.
      RESULTS: The images of 70 patients were analysed. Intraocular pressure reduced
      from 22.25 (SD 3.76) mm Hg, at the time of preoperative imaging to 15.27 (SD
      4.96) mm Hg at 3 months, 14.38 (SD 3.89) mm Hg at 1 year, and 13.80 (SD 3.54) mm
      Hg at 2 years after trabeculectomy. An increase in rim area and rim volume was
      present at all time points after surgery, but was only found to be statistically
      significant at 2 years after surgery. Maximum depth of cup reduced by month 3 and
      month 12, but showed a slight increase at 2 years after surgery, although this
      was still lower than the preoperative measure. Segmental analysis found a
      significant change in rim volume in the nasal, inferonasal, superonasal, and
      superotemporal regions at 2 years after surgery. No significant regional
      localisation for change was found at any other time point or in any other
      parameter investigated. CONCLUSIONS: Reversal of disc cupping is present at 2
      years after trabeculectomy. The factor most influencing change is reduction of
      intraocular pressure. Segmental analysis showed that change in rim volume was
      greatest in the nasal, inferonasal, superonasal and superotemporal regions at 2
      years.

PMID- 11466256
TI  - A 7 year prospective comparative study of three topical beta blockers in the
      management of primary open angle glaucoma.
AB  - AIM: To determine the long term efficacy of monotherapy with topically applied
      beta blocking agents and to determine whether selective beta blockers were able
      to preserve the visual field more effectively than non-selective agents. METHOD:
      A prospective randomised, open, comparative study of three topically applied beta
      blockers-timolol, betaxolol, and carteolol-was carried out on 153 patients (280
      eyes) with newly diagnosed open angle glaucoma. Those patients who were not
      withdrawn were followed by the same observers for a minimum of 2 years and a
      maximum of 7 years, with clinical observations, Goldmann tonometry and 24.2
      Humphrey visual field analysis. RESULTS: All three drugs lowered the IOP
      significantly from untreated levels but betaxolol took up to 12 months in some
      instances to reach the maximum pressure reduction. After 7 years only 43% of the
      eyes begun on timolol, 34% of those started on carteolol, and 29% of those on
      betaxolol were still being treated with these medications alone. Visual fields
      were analysed throughout the trial by CPSD and MD and at the end by linear
      regression analysis (PROGRESSOR). The visual fields remained the same without
      apparent improvement or deterioration throughout the period of follow up. Eight
      patients (11 eyes) were withdrawn because of continuing field loss in spite of
      reduction in IOP (six using carteolol and five using betaxolol). CONCLUSIONS:
      Analysis shows that less than half the eyes initially treated with topical beta
      blockers might be expected to still be being treated with their original
      medication after 5 years. The rest required either additional medication or
      trabeculectomy. There was no statistically significant improvement or
      deterioration in the visual fields over a 7 year period. On the evidence of this
      trial there are no particular advantages in using selective beta blockers.

PMID- 11466257
TI  - Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular
      degeneration.
AB  - BACKGROUND: A long term project was initiated to identify and to characterise
      genes that are expressed exclusively or preferentially in the retina as
      candidates for a genetic susceptibility to age related macular degeneration
      (AMD). A transcript represented by a cluster of five human expressed sequence
      tags (ESTs) derived exclusively from retinal cDNA libraries was identified.
      METHODS: Northern blot and RT-PCR analyses confirmed preferential retinal
      expression of the gene, which encodes a G protein coupled receptor, GPR75.
      Following isolation of the full length cDNA and determination of the genomic
      organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD
      patients and 252 controls from Germany, the United States, and Italy. Employed
      methods included single stranded conformational polymorphism (SSCP) analysis,
      denaturing high performance liquid chromatography (DHPLC), and direct sequencing.
      RESULTS: Nine different sequence variations were identified in patients and
      control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent
      polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P,
      and Q234X) were found once in single AMD patients and were considered variants
      that could affect the protein function and potentially cause retinal pathology.
      CONCLUSION: The presence of six potential pathogenic variants in a cohort of 535
      AMD patients alone does not provide statistically significant evidence for the
      association of sequence variation in GPR75 with genetic predisposition to AMD.
      However, a possible connection between the variants and age related retinal
      pathology cannot be discarded. Functional studies are needed to clarify the role
      of GPR75 in retinal physiology.

PMID- 11466258
TI  - Ultrasound biomicroscopy of the peripheral retina and the ciliary body in
      degenerative retinoschisis associated with pars plana cysts.
AB  - AIM: To evaluate the ciliary body and peripheral retina in degenerative
      retinoschisis associated with pars plana cysts using ultrasound biomicroscopy
      (UBM). METHODS: 18 eyes of 12 patients with degenerative retinoschisis associated
      with pars plana cysts were selected through binocular indirect ophthalmoscopy and
      Goldmann three mirror lens examination, both with scleral depression. These
      patients were studied in detail with UBM. RESULTS: Study of the ciliary body with
      UBM showed pars plana cysts of different size and uneven shape. In cross sections
      the morphology of pars plana cysts in detail and the close relation of the cysts
      with the oral region and the peripheral retina, where areas of cystoid
      degeneration and retinoschisis were present, were observed. In transverse
      sections three main morphological aspects of pars plana cysts could be
      differentiated ("isolated," "confluent," and "clustered" cysts). Furthermore,
      ultrabiomicroscopy allowed differential diagnosis between retinoschisis and
      associated retinal detachment in six eyes. CONCLUSIONS: The study of peripheral
      degenerative retinoschisis and pars plana cysts is possible in vivo by means of
      UBM, showing the detailed morphology of the lesions (not otherwise evident
      through ophthalmoscopic examination) and the close relation between pars plana
      cysts, cystoid degeneration, and peripheral retinoschisis.

PMID- 11466259
TI  - Meta-analysis of randomised controlled trials comparing latanoprost with timolol
      in the treatment of patients with open angle glaucoma or ocular hypertension.
AB  - AIM: To evaluate the comparative efficacy and tolerance of latanoprost versus
      timolol through a meta-analysis of randomised controlled trials (RCTs). METHODS:
      Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of
      results from head to head comparison studies. Quality of trials was assessed
      based on randomisation, masking, and withdrawal. Sensitivity analyses were used
      to estimate the effects of quality of study on outcomes. The data sources were
      Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and
      Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma
      or ocular hypertension reported in 11 trials of latanoprost versus timolol. The
      main outcome measures were (i) percentage intraocular pressure (IOP) reduction
      for efficacy; (ii) relative risk, risk difference, and number needed to harm for
      side effects such as hyperaemia, conjunctivitis, increased pigmentation,
      hypotension, and bradycardia expressed as dichotomous outcomes; and (iii)
      reduction in systemic blood pressure and heart rate as side effects. RESULTS:
      Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The
      percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost
      and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP
      reduction between the two treatments were 5.0 (95% confidence intervals 2.8,
      7.3). However, latanoprost caused iris pigmentation in more patients than timolol
      (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk
      with latanoprost reached 18% (51/277). Hyperaemia was also more often observed
      with latanoprost (relative risk =2.20, 95% confidence intervals 1.33, 3.64).
      Timolol caused a significant reduction in heart rate of 4 beats/minute (95%
      confidence interval 2, 6). CONCLUSION: This meta-analysis suggests that
      latanoprost is more effective than timolol in lowering IOP. However, it often
      causes iris pigmentation. While current evidence suggests that this pigmentation
      is benign, careful lifetime evaluation of patients is still justified.

PMID- 11466260
TI  - Gene transfer by viral vectors into blood vessels in a rat model of retinopathy
      of prematurity.
AB  - AIMS: To test the feasibility of gene transfer into hyaloid blood vessels and
      into preretinal neovascularisation in a rat model of retinopathy of prematurity
      (ROP), using different viral vectors. METHODS: Newborn rats were exposed to
      alternating hypoxic and hyperoxic conditions in order to induce ocular
      neovascularisation (ROP rats). Adenovirus, herpes simplex, vaccinia, and
      retroviral (MuLV based) vectors, all carrying the beta galactosidase (beta-gal)
      gene, were injected intravitreally on postnatal day 18 (P18). Two sets of
      controls were also examined: P18 ROP rats injected with saline and P18 rats that
      were raised in room air before the viral vectors or saline were injected. Two
      days after injection, the rats were killed, eyes enucleated, and beta-gal
      expression was examined by X-gal staining in whole mounts and in histological
      sections. RESULTS: Intravitreal injection of the adenovirus and vaccinia vectors
      yielded marked beta-gal expression in hyaloid blood vessels in the rat ROP model.
      Retinal expression of beta-gal with these vectors was limited almost exclusively
      to the vicinity of the injection site. Injection of herpes simplex yielded a
      punctuate pattern of beta-gal expression in the retina but not in blood vessels.
      No significant beta-gal expression occurred in rat eyes injected with the
      retroviral vector. CONCLUSIONS: Adenovirus is an efficient vector for gene
      transfer into blood vessels in an animal model of ROP. This may be a first step
      towards utilising gene transfer as a tool for modulating ocular
      neovascularisation for experimental and therapeutic purposes.

PMID- 11466261
TI  - In situ immunohistochemical study of Bcl-2 and heat shock proteins in human
      corneal endothelial cells during corneal storage.
AB  - AIM: To investigate the expression of Bcl-2 and heat shock proteins (HSPs), which
      are known to increase cell survival, in human corneal endothelial cells (HCECs)
      of corneas stored in organ culture. METHODS: 32 paired corneas were randomly
      assigned to either a short or a long storage time. The flat mounts of endothelium
      were examined after immunostaining with monoclonal antibodies to Bcl-2 and HSP
      27, 60, 70, and 90. RESULTS: HCECs expressed generally all the proteins studied.
      Bcl-2 expression was weaker in the long stored corneas (p=0.035). There was no
      relation between immunostaining, age, sex, or death to culture time. Frequently
      some Descemet membranes carried negative cells preferentially located in folds
      and exhibiting morphological changes consistent with swelling cells corresponding
      to early stages of apoptosis. CONCLUSION: Expression of these cytoprotective
      proteins reflects the high level of HCEC resistance to stresses induced by organ
      culture. The decreased immunostaining of Bcl-2 in the long storage group could
      act in cellular loss currently observed with storage time. The negativity of Bcl
      2 and HSP labelling in corneal folding may be related to apoptosis.

PMID- 11466263
TI  - TTT and CNV.

PMID- 11466262
TI  - Single dose intranasal administration of retinal autoantigen generates a rapid
      accumulation and cell activation in draining lymph node and spleen: implications
      for tolerance therapy.
AB  - BACKGROUND/AIMS: A single intranasal delivery of retinal autoantigen suppresses
      effectively experimental autoimmune uveoretinitis (EAU). To further unravel
      underlying mechanisms the authors wished to determine, firstly, the kinetics of
      antigen delivery and, secondly, the early cellular responses involved in the
      initial stages of nasal mucosal tolerance induction. METHODS: Flow cytometry,
      cell proliferation assays, and microscopy were used to track antigen following a
      single, intranasal dose of Alexa-488 labelled retinal antigen. RESULTS: A rapid
      accumulation of antigen within both superficial cervical lymph nodes (SCLN) and
      spleen was observed after 30 minutes. Significant proliferative responses to IRBP
      were elicited by 48 hours indicating that systemic priming of naive T cells to
      retinal antigen had occurred. Cell activation was further confirmed by
      immunoprecipitation studies, which demonstrated phosphorylation of STAT4 but not
      STAT6 in both lymph nodes and spleen. However, at 24 hours, STAT4
      heterodimerisation with STAT 3 was only observed in spleen. CONCLUSIONS: The
      results provide novel evidence that following a single intranasal application
      rapid transfer of antigen occurs. Resulting T cell proliferation develops
      consequent to differential cell signalling in SCLN and spleen. Further
      understanding of these underlying cellular mechanisms, in particular as is
      inferred by the results the contribution of local versus systemic tolerance
      induction, may assist in strategies to clinically apply mucosal tolerance therapy
      successfully.

PMID- 11466264
TI  - Further pathophysiological insights into age related macular degeneration.

PMID- 11466265
TI  - A new colour vision arrangement test to detect functional changes in diabetic
      macular oedema.

PMID- 11466269
TI  - More than one way to sense chemicals.

PMID- 11466270
TI  - Xenorhabdus nematophilus as a model for host-bacterium interactions: rpoS is
      necessary for mutualism with nematodes.
AB  - Xenorhabdus nematophilus, a gram-negative bacterium, is a mutualist of
      Steinernema carpocapsae nematodes and a pathogen of larval-stage insects. We use
      this organism as a model of host-microbe interactions to identify the functions
      bacteria require for mutualism, pathogenesis, or both. In many gram-negative
      bacteria, the transcription factor sigma(S) controls regulons that can mediate
      stress resistance, survival, or host interactions. Therefore, we examined the
      role of sigma(S) in the ability of X. nematophilus to interact with its hosts. We
      cloned, sequenced, and disrupted the X. nematophilus rpoS gene that encodes
      sigma(S). The X. nematophilus rpoS mutant pathogenized insects as well as its
      wild-type parent. However, the rpoS mutant could not mutualistically colonize
      nematode intestines. To our knowledge, this is the first report of a specific
      allele that affects the ability of X. nematophilus to exist within nematode
      intestines, an important step in understanding the molecular mechanisms of this
      association.

PMID- 11466271
TI  - Requirement of novel competence genes pilT and pilU of Pseudomonas stutzeri for
      natural transformation and suppression of pilT deficiency by a hexahistidine tag
      on the type IV pilus protein PilAI.
AB  - The ubiquitous species Pseudomonas stutzeri has type IV pili, and these are
      essential for the natural transformation of the cells. An absolute transformation
      deficient mutant obtained after transposon mutagenesis had an insertion in a gene
      which was termed pilT. The deduced amino acid sequence has identity with PilT of
      Pseudomonas aeruginosa (94%), Neisseria gonorrhoeae (67%), and other gram
      negative species and it contains a nucleotide-binding motif. The mutant was
      hyperpiliated but defective for further pilus-associated properties, such as
      twitching motility and plating of pilus-specific phage PO4. [(3)H]thymidine
      labeled DNA was bound by the mutant but not taken up. Downstream of pilT a gene,
      termed pilU, coding for a putative protein with 88% amino acid identity with PilU
      of P. aeruginosa was identified. Insertional inactivation did not affect
      piliation, twitching motility, or PO4 infection but reduced transformation to
      about 10%. The defect was fully complemented by PilU of nontransformable P.
      aeruginosa. When the pilAI gene (coding for the type IV pilus prepilin) was
      manipulated to code for a protein in which the six C-terminal amino acids were
      replaced by six histidine residues and then expressed from a plasmid, it gave a
      nonpiliated and twitching motility-defective phenotype in pilAI::Gm(r) cells but
      allowed transformability. Moreover, the mutant allele suppressed the absolute
      transformation deficiency caused by the pilT mutation. Considering the
      hypothesized role of pilT(+) in pilus retraction and the presumed requirement of
      retraction for DNA uptake, it is proposed that the pilT-independent
      transformation is promoted by PilA mutant protein either as single molecules or
      as minimal pilin assembly structures in the periplasm which may resemble
      depolymerized pili and that these cause the outer membrane pores to open for DNA
      entry.

PMID- 11466272
TI  - Treponema pallidum 3-phosphoglycerate mutase is a heat-labile enzyme that may
      limit the maximum growth temperature for the spirochete.
AB  - In the causative agent of syphilis, Treponema pallidum, the gene encoding 3
      phosphoglycerate mutase, gpm, is part of a six-gene operon (tro operon) that is
      regulated by the Mn-dependent repressor TroR. Since substrate-level
      phosphorylation via the Embden-Meyerhof pathway is the principal way to generate
      ATP in T. pallidum and Gpm is a key enzyme in this pathway, Mn could exert a
      regulatory effect on central metabolism in this bacterium. To study this, T.
      pallidum gpm was cloned, Gpm was purified from Escherichia coli, and antiserum
      against the recombinant protein was raised. Immunoblots indicated that Gpm was
      expressed in freshly extracted infective T. pallidum. Enzyme assays indicated
      that Gpm did not require Mn(2+) while 2,3-diphosphoglycerate (DPG) was required
      for maximum activity. Consistent with these observations, Mn did not copurify
      with Gpm. The purified Gpm was stable for more than 4 h at 25 degrees C, retained
      only 50% activity after incubation for 20 min at 34 degrees C or 10 min at 37
      degrees C, and was completely inactive after 10 min at 42 degrees C. The
      temperature effect was attenuated when 1 mM DPG was added to the assay mixture.
      The recombinant Gpm from pSLB2 complemented E. coli strain PL225 (gpm) and
      restored growth on minimal glucose medium in a temperature-dependent manner.
      Increasing the temperature of cultures of E. coli PL225 harboring pSLB2 from 34
      to 42 degrees C resulted in a 7- to 11-h period in which no growth occurred
      (compared to wild-type E. coli). These data suggest that biochemical properties
      of Gpm could be one contributing factor to the heat sensitivity of T. pallidum.

PMID- 11466273
TI  - Fructose uptake in Sinorhizobium meliloti is mediated by a high-affinity ATP
      binding cassette transport system.
AB  - By transposon mutagenesis, we have isolated a mutant of Sinorhizobium meliloti
      which is totally unable to grow on fructose as sole carbon source as a
      consequence of its inability to transport this sugar. The cloning and sequencing
      analysis of the chromosomal DNA region flanking the TnphoA insertion revealed the
      presence of six open reading frames (ORFs) organized in two loci, frcRS and
      frcBCAK, transcribed divergently. The frcBCA genes encode the characteristic
      components of an ATP-binding cassette transporter (FrcB, a periplasmic substrate
      binding protein, FrcC, an integral membrane permease, and FrcA, an ATP-binding
      cytoplasmic protein), which is the unique high-affinity (K(m) of 6 microM)
      fructose uptake system in S. meliloti. The FrcK protein shows homology with some
      kinases, while FrcR is probably a transcriptional regulator of the repressor-ORF
      kinase family. The expression of S. meliloti frcBCAK in Escherichia coli, which
      transports fructose only via the phosphotransferase system, resulted in the
      detection of a periplasmic fructose binding activity, demonstrating that FrcB is
      the binding protein of the Frc transporter. The analysis of substrate
      specificities revealed that the Frc system is also a high-affinity transporter
      for ribose and mannose, which are both fructose competitors for the binding to
      the periplasmic FrcB protein. However, the Frc mutant was still able to grow on
      these sugars as sole carbon source, demonstrating the presence of at least one
      other uptake system for mannose and ribose in S. meliloti. The expression of the
      frcBC genes as determined by measurements of alkaline phosphatase activity was
      shown to be induced by mannitol and fructose, but not by mannose, ribose,
      glucose, or succinate, suggesting that the Frc system is primarily targeted
      towards fructose. Neither Nod nor Fix phenotypes were impared in the TnphoA
      mutant, demonstrating that fructose uptake is not essential for nodulation and
      nitrogen fixation, although FrcB protein is expressed in bacteroids isolated from
      alfalfa nodulated by S. meliloti wild-type strains.

PMID- 11466274
TI  - Insertion-duplication mutagenesis of neisseria: use in characterization of DNA
      transfer genes in the gonococcal genetic island.
AB  - We created plasmids for use in insertion-duplication mutagenesis (IDM) of
      Neisseria gonorrhoeae. This mutagenesis method has the advantage that it requires
      only a single cloning step prior to transformation into gonococci. Chromosomal
      DNA cloned into the plasmid directs insertion into the chromosome at the site of
      homology by a single-crossover (Campbell-type) recombination event. Two of the
      vectors contain an erythromycin resistance gene, ermC, with a strong promoter and
      in an orientation such that transcription will proceed into the cloned insert.
      Thus, these plasmids can be used to create insertions that are effectively
      nonpolar on the transcription of downstream genes. In addition to the improved
      ermC, the vector contains two copies of the neisserial DNA uptake sequence to
      facilitate high-frequency DNA uptake during transformation. Using various
      chromosomal DNA insert sizes, we have determined that even small inserts can
      target insertion mutation by this method and that the insertions are stably
      maintained in the gonococcal chromosome. We have used IDM to create knockouts in
      two genes in the gonococcal genetic island (GGI) and to clone additional regions
      of the GGI by a chromosome-walking procedure. Phenotypic characterization of traG
      and traH mutants suggests a role for the encoded proteins in DNA secretion by a
      novel type IV secretion system.

PMID- 11466275
TI  - matB, a common fimbrillin gene of Escherichia coli, expressed in a genetically
      conserved, virulent clonal group.
AB  - A novel fimbrial type in Escherichia coli was identified and characterized. The
      expression of the fimbria was associated with the O18acK1H7 clonal group of E.
      coli, which cause newborn meningitis and septicemia when grown at low
      temperature; hence, it was named the Mat (meningitis associated and temperature
      regulated) fimbria. The fimbriae were purified from a fimA::cat sfaA::Gm fliC::St
      derivative of the O18K1H7 isolate E. coli IHE 3034. The purified Mat fimbrillin
      had an apparent molecular mass of 18 kDa and did not serologically cross-react
      with the type 1 or S fimbria of the same strain. The matB gene encoding the major
      fimbrillin was cloned from the genomic DNA of the fimA::cat sfaA::Gm fliC::St
      derivative of IHE 3034. The predicted MatB sequence was of 195 amino acids,
      contained a signal sequence of 22 residues, and did not show significant homology
      to any of the previously characterized fimbrial proteins. The DNA sequence of
      matB was 97.8% identical to a region from nucleotides 17882 to 18469 in the 6- to
      8-min region of the E. coli K-12 chromosome, reported to encode a hypothetical
      protein. The 7-kb DNA fragment containing matB of IHE 3034 was found by
      restriction mapping and partial DNA sequencing to be highly similar to the
      corresponding region in the K-12 chromosome. Trans complementation of the
      matB::cat mutation in the IHE 3034 chromosome showed that matB in combination
      with matA or matC restored surface expression of the Mat fimbria. A total of 27
      isolates representing K-12 strains and the major pathogroups of E. coli were
      analyzed for the presence of a matB homolog as well as for expression of the Mat
      fimbria. A conserved matB homolog was found in 25 isolates; however, expression
      of the Mat fimbriae was detected only in the O18acK1H7 isolates. Expression of
      the Mat fimbria was temperature regulated, with no or a very small amount of
      fimbriae or intracellular MatB fimbrillin being detected in cells cultivated at
      37(o)C. Reverse transcriptase PCR and complementation assays with mat genes
      controlled by the inducible trc promoter indicated that regulation of Mat fimbria
      expression involved both transcriptional and posttranscriptional events.

PMID- 11466276
TI  - Characterization of VPI pathogenicity island and CTXphi prophage in environmental
      strains of Vibrio cholerae.
AB  - Environmental isolates of Vibrio cholerae of eight randomly amplified polymorphic
      DNA (RAPD) fingerprint types from Calcutta, India, that were unusual in
      containing toxin-coregulated pilus or cholera toxin genes but not O1 or O139
      antigens of epidemic strains were studied by PCR and sequencing to gain insights
      into V. cholerae evolution. We found that each isolate contained a variant form
      of the VPI pathogenicity island. Distinguishing features included (i) four new
      alleles of tcpF (which encodes secreted virulence protein; its exact function is
      unknown), 20 to 70% divergent (at the protein level) from each other and
      canonical tcpF; (ii) a new allele of toxT (virulence regulatory gene), 36%
      divergent (at the protein level) in its 5' half and nearly identical in its 3'
      half to canonical toxT; (iii) a new tcpA (pilin) gene; and (iv) four variant
      forms of a regulatory sequence upstream of toxT. Also found were transpositions
      of an IS903-related element and function-unknown genes to sites in VPI. Cholera
      toxin (ctx) genes were found in isolates of two RAPD types, in each case embedded
      in CTXphi-like prophages. Fragments that are inferred to contain only putative
      repressor, replication, and integration genes were present in two other RAPD
      types. New possible prophage repressor and replication genes were also
      identified. Our results show marked genetic diversity in the virulence-associated
      gene clusters found in some nonepidemic V. cholerae strains, suggest that some of
      these genes contribute to fitness in nature, and emphasize the potential
      importance of interstrain gene exchange in the evolution of this species.

PMID- 11466277
TI  - Changes in rRNA levels during stress invalidates results from mRNA blotting:
      fluorescence in situ rRNA hybridization permits renormalization for estimation of
      cellular mRNA levels.
AB  - Regulation of gene expression can be analyzed by a number of different
      techniques. Some techniques monitor the level of specific mRNA directly, and
      others monitor indirectly by determining the level of enzymes encoded by the
      mRNA. Each method has its own inherent way of normalization. When results
      obtained by these techniques are compared between experiments in which
      differences in growth rates, strains, or stress treatments occur, the
      normalization procedure may have a significant impact on the results. In this
      report we present a solution to the normalization problem in RNA slot blotting
      experiments, in which mRNA levels routinely are normalized to a fixed amount of
      extracted total RNA. The cellular levels of specific mRNA species were estimated
      using a renormalization with the total RNA content per cell. By a combination of
      fluorescence in situ rRNA hybridization, which estimates the relative level of
      rRNA per cell, and slot blotting to rRNA probes, which estimates the level of
      rRNA per extracted total RNA, the amount of RNA per cell was calculated in a
      series of heat shock experiments with the gram-positive bacterium Lactococcus
      lactis. It was found that the level of rRNA per cell decreased to 30% in the
      course of the heat shock. This lowered ribosome level led to a decrease in the
      total RNA content, resulting in a gradually increasing overestimation of the mRNA
      levels throughout the experiment. Using renormalized cellular mRNA levels, the
      HrcA-mediated regulation of the genes in the hrcA-grpE-dnaK operon was analyzed.
      The hybridization data suggested a complex heat shock regulation indicating that
      the mRNA levels continued to rise after 30 min, but after renormalization the
      calculated average cellular levels exhibited a much simpler induction pattern,
      eventually attaining a moderately increased value.

PMID- 11466278
TI  - Membrane topology of the Streptomyces lividans type I signal peptidases.
AB  - Most bacterial membranes contain one or two type I signal peptidases (SPases) for
      the removal of signal peptides from export proteins. For Streptomyces lividans,
      four different type I SPases (denoted SipW, SipX, SipY, and SipZ) were previously
      described. In this communication, we report the experimental determination of the
      membrane topology of these SPases. A protease protection assay of SPase
      tendamistat fusions confirmed the presence of the N- as well as the C-terminal
      transmembrane anchor for SipY. SipX and SipZ have a predicted topology similar to
      that of SipY. These three S. lividans SPases are currently the only known
      prokaryotic-type type I SPases of gram-positive bacteria with a C-terminal
      transmembrane anchor, thereby establishing a new subclass of type I SPases. In
      contrast, S. lividans SipW contains only the N-terminal transmembrane segment,
      similar to most type I SPases of gram-positive bacteria. Functional analysis
      showed that the C-terminal transmembrane anchor of SipY is important to enhance
      the processing activity, both in vitro as well as in vivo. Moreover, for the S.
      lividans SPases, a relation seems to exist between the presence or absence of the
      C-terminal anchor and the relative contributions to the total SPase processing
      activity in the cell. SipY and SipZ, two SPases with a C-terminal anchor, were
      shown to be of major importance to the cell. Accordingly, for SipW, missing the C
      terminal anchor, a minor role in preprotein processing was found.

PMID- 11466279
TI  - Domain interactions in the yeast ATP binding cassette transporter Ycf1p:
      intragenic suppressor analysis of mutations in the nucleotide binding domains.
AB  - The yeast cadmium factor (Ycf1p) is a vacuolar ATP binding cassette (ABC)
      transporter required for heavy metal and drug detoxification. Cluster analysis
      shows that Ycf1p is strongly related to the human multidrug-associated protein
      (MRP1) and cystic fibrosis transmembrane conductance regulator and therefore may
      serve as an excellent model for the study of eukaryotic ABC transporter structure
      and function. Identifying intramolecular interactions in these transporters may
      help to elucidate energy transfer mechanisms during transport. To identify
      regions in Ycf1p that may interact to couple ATPase activity to substrate binding
      and/or movement across the membrane, we sought intragenic suppressors of ycf1
      mutations that affect highly conserved residues presumably involved in ATP
      binding and/or hydrolysis. Thirteen intragenic second-site suppressors were
      identified for the D777N mutation which affects the invariant Asp residue in the
      Walker B motif of the first nucleotide binding domain (NBD1). Two of the
      suppressor mutations (V543I and F565L) are located in the first transmembrane
      domain (TMD1), nine (A1003V, A1021T, A1021V, N1027D, Q1107R, G1207D, G1207S,
      S1212L, and W1225C) are found within TMD2, one (S674L) is in NBD1, and another
      one (R1415G) is in NBD2, indicating either physical proximity or functional
      interactions between NBD1 and the other three domains. The original D777N mutant
      protein exhibits a strong defect in the apparent affinity for ATP and V(max) of
      transport. The phenotypic characterization of the suppressor mutants shows that
      suppression does not result from restoring these alterations but rather from a
      change in substrate specificity. We discuss the possible involvement of Asp777 in
      coupling ATPase activity to substrate binding and/or transport across the
      membrane.

PMID- 11466280
TI  - Transduction by phiBB-1, a bacteriophage of Borrelia burgdorferi.
AB  - We previously described a bacteriophage of the Lyme disease agent Borrelia
      burgdorferi designated phiBB-1. This phage packages the host complement of the 32
      kb circular plasmids (cp32s), a group of homologous molecules found throughout
      the genus Borrelia. To demonstrate the ability of phiBB-1 to package and
      transduce DNA, a kanamycin resistance cassette was inserted into a cloned
      fragment of phage DNA, and the resulting construct was transformed into B.
      burgdorferi CA-11.2A cells. The kan cassette recombined into a resident cp32 and
      was stably maintained. The cp32 containing the kan cassette was packaged by phiBB
      1 released from this B. burgdorferi strain. phiBB-1 has been used to transduce
      this antibiotic resistance marker into naive CA-11.2A cells, as well as two other
      strains of B. burgdorferi. This is the first direct evidence of a mechanism for
      lateral gene transfer in B. burgdorferi.

PMID- 11466281
TI  - Identification and characterization of a monofunctional glycosyltransferase from
      Staphylococcus aureus.
AB  - A gene (mgt) encoding a monofunctional glycosyltransferase (MGT) from
      Staphylococcus aureus has been identified. This first reported gram-positive MGT
      shared significant homology with several MGTs from gram-negative bacteria and the
      N-terminal glycosyltransferase domain of class A high-molecular-mass penicillin
      binding proteins from different species. S. aureus MGT contained an N-terminal
      hydrophobic domain perhaps involved with membrane association. It was expressed
      in Escherichia coli cells as a truncated protein lacking the hydrophobic domain
      and purified to homogeneity. Analysis by circular dichroism revealed that
      secondary structural elements of purified truncated S. aureus MGT were consistent
      with predicted structural elements, indicating that the protein might exhibit the
      expected folding. In addition, purified S. aureus MGT catalyzed incorporation of
      UDP-N-acetylglucosamine into peptidoglycan, proving that it was enzymatically
      active. MGT activity was inhibited by moenomycin A, and the reaction product was
      sensitive to lysozyme treatment. Moreover, a protein matching the calculated
      molecular weight of S. aureus MGT was identified from an S. aureus cell lysate
      using antibodies developed against purified MGT. Taken together, our results
      suggest that this enzyme is natively present in S. aureus cells and that it may
      play a role in bacterial cell wall biosynthesis.

PMID- 11466282
TI  - Genetic studies of mrp, a locus essential for cellular aggregation and
      sporulation of Myxococcus xanthus.
AB  - Under starvation conditions, Myxococcus xanthus undergoes a complex developmental
      process which includes cellular aggregation and sporulation. A transposon
      insertion mutant (the Tn5-Omega280 mutant) with defects in both aggregation and
      sporulation was analyzed in this study. The Tn5-Omega280 mutant was found to have
      a disrupted NtrC-like response regulator designated Myxococcus regulatory protein
      B (mrpB). Further sequencing analyses revealed a histidine kinase homolog (mrpA)
      immediately upstream of mrpB and a cyclic AMP receptor protein-like
      transcriptional regulator (mrpC) downstream of mrpB. In-frame deletion analyses
      revealed that both the mrpB and mrpC genes were required for cellular aggregation
      and sporulation but that only mrpA was required for sporulation only. Site
      specific mutagenesis of the putative phosphorylation site of MrpB, D58, showed
      that a D58A mutation caused defects in both aggregation and sporulation but that
      a D58E mutation resulted in only a sporulation defect. Further genetic and
      molecular analyses with reporter genes and reverse transcription-PCR indicated
      that mrpA and mrpB are cotranscribed but that mrpC is transcribed independently
      and that all of these genes are developmentally regulated. In addition, MrpB is
      essential for transcription of mrpC and MrpC regulates its own transcription.
      These data indicate that Mrp proteins are important components required for M.
      xanthus development. The complicated interaction between Mrp proteins may play an
      important role in regulating developmental gene expression in M. xanthus.

PMID- 11466283
TI  - Identification and mutagenesis by allelic exchange of choE, encoding a
      cholesterol oxidase from the intracellular pathogen Rhodococcus equi.
AB  - The virulence mechanisms of the facultative intracellular parasite Rhodococcus
      equi remain largely unknown. Among the candidate virulence factors of this
      pathogenic actinomycete is a secreted cholesterol oxidase, a putative membrane
      damaging toxin. We identified and characterized the gene encoding this enzyme,
      the choE monocistron. Its protein product, ChoE, is homologous to other secreted
      cholesterol oxidases identified in Brevibacterium sterolicum and Streptomyces
      spp. ChoE also exhibits significant similarities to putative cholesterol oxidases
      encoded by Mycobacterium tuberculosis and Mycobacterium leprae. Genetic tools for
      use with R. equi are poorly developed. Here we describe the first targeted
      mutagenesis system available for this bacterium. It is based on a suicide
      plasmid, a selectable marker (the aacC4 apramycin resistance gene from
      Salmonella), and homologous recombination. The choE allele was disrupted by
      insertion of the aacC4 gene, cloned in pUC19 and introduced by electroporation in
      R. equi. choE recombinants were isolated at frequencies between 10(-2) and 10(
      3). Twelve percent of the recombinants were double-crossover choE mutants. The
      choE mutation was associated with loss of cooperative (CAMP-like) hemolysis with
      sphingomyelinase-producing bacteria (Listeria ivanovii). Functional
      complementation was achieved by expression of choE from pVK173-T, a pAL5000
      derivative conferring hygromycin resistance. Our data demonstrate that ChoE is an
      important cytolytic factor for R. equi. The highly efficient targeted mutagenesis
      procedure that we used to generate choE isogenic mutants will be a valuable tool
      for the molecular analysis of R. equi virulence.

PMID- 11466284
TI  - Dual repression by Fe(2+)-Fur and Mn(2+)-MntR of the mntH gene, encoding an NRAMP
      like Mn(2+) transporter in Escherichia coli.
AB  - The uptake of Mn(2+), a cofactor for several enzymes in Escherichia coli, is
      mediated by MntH, a proton-dependent metal transporter, which also recognizes
      Fe(2+) with lower affinity. MntH belongs to the NRAMP family of eukaryotic Fe(2+)
      and Mn(2+) transporters. In E. coli strains with chromosomal mntH-lacZ fusions,
      mntH was partially repressed by both Mn(2+) and Fe(2+). Inactivation of fur
      resulted in the loss of Fe(2+)-dependent repression of mntH transcription,
      demonstrating that Fe(2+) repression depends on the global iron regulator Fur.
      However, these fur mutants still showed Mn(2+)-dependent repression of mntH. The
      Mn(2+)-responsive transcriptional regulator of mntH was identified as the gene
      product of o155 (renamed MntR). mntR mutants were impaired in Mn(2+) but not
      Fe(2+) repression of mntH transcription. Binding of purified MntR to the mntH
      operator was manganese dependent. The binding region was localized by DNase I
      footprinting analysis and covers a nearly perfect palindrome. The Fur binding
      site, localized within 22 nucleotides of the mntH operator by in vivo operator
      titration assays, resembles the Fur-box consensus sequence.

PMID- 11466285
TI  - Developmental gene expression in Bacillus subtilis crsA47 mutants reveals glucose
      activated control of the gene for the minor sigma factor sigma(H).
AB  - The presence of excess glucose in growth media prevents normal sporulation of
      Bacillus subtilis. The crsA47 mutation, located in the gene for the vegetative
      phase sigma factor (sigma(A)) results in a glucose-resistant sporulation
      phenotype. As part of a study of the mechanisms whereby the mutation in sigma(A)
      overcomes glucose repression of sporulation, we examined the expression of genes
      involved in sporulation initiation in the crsA47 background. The crsA47 mutation
      had a significant impact on a variety of genes. Changes to stage II gene
      expression could be linked to alterations in the expression of the sinI and sinR
      genes. In addition, there was a dramatic increase in the expression of genes
      dependent on the minor sigma factor sigma(H). This latter change was paralleled
      by the pattern of spo0H gene transcription in cells with the crsA47 mutation. In
      vitro analysis of RNA polymerase containing sigma(A47) indicated that it did not
      have unusually high affinity for the spo0H gene promoter. The in vivo pattern of
      spo0H expression is not predicted by the known regulatory constraints on spo0H
      and suggests novel regulation mechanisms that are revealed in the crsA47
      background.

PMID- 11466286
TI  - Genome sequence and comparative analysis of the solvent-producing bacterium
      Clostridium acetobutylicum.
AB  - The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum
      ATCC 824 has been determined by the shotgun approach. The genome consists of a
      3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes
      responsible for solvent production. Comparison of C. acetobutylicum to Bacillus
      subtilis reveals significant local conservation of gene order, which has not been
      seen in comparisons of other genomes with similar, or, in some cases closer,
      phylogenetic proximity. This conservation allows the prediction of many
      previously undetected operons in both bacteria. However, the C. acetobutylicum
      genome also contains a significant number of predicted operons that are shared
      with distantly related bacteria and archaea but not with B. subtilis.
      Phylogenetic analysis is compatible with the dissemination of such operons by
      horizontal transfer. The enzymes of the solventogenesis pathway and of the
      cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not
      previously represented in the collection of complete genomes. These enzymes show
      a complex pattern of evolutionary affinities, emphasizing the role of lateral
      gene exchange in the evolution of the unique metabolic profile of the bacterium.
      Many of the sporulation genes identified in B. subtilis are missing in C.
      acetobutylicum, which suggests major differences in the sporulation process.
      Thus, comparative analysis reveals both significant conservation of the genome
      organization and pronounced differences in many systems that reflect unique
      adaptive strategies of the two gram-positive bacteria.

PMID- 11466287
TI  - Molecular, antigenic, and functional analyses of Omp2b porin size variants of
      Brucella spp.
AB  - Omp2a and Omp2b are highly homologous porins present in the outer membrane of the
      bacteria from the genus Brucella, a facultative intracellular pathogen. The genes
      coding for these proteins are closely linked in the Brucella genome and oriented
      in opposite directions. In this work, we present the cloning, purification, and
      characterization of four Omp2b size variants found in various Brucella species,
      and we compare their antigenic and functional properties to the Omp2a and Omp2b
      porins of Brucella melitensis reference strain 16M. The variation of the Omp2a
      and Omp2b porin sequences among the various strains of the genus Brucella seems
      to result mostly from multiple gene conversions between the two highly homologous
      genes. As shown in this study, this phenomenon has led to the creation of natural
      Omp2a and Omp2b chimeric proteins in Omp2b porin size variants. The comparison by
      liposome swelling assay of the porins sugar permeability suggested a possible
      functional differences between Omp2a and Omp2b, with Omp2a showing a more
      efficient pore in sugar diffusion. The sequence variability in the Omp2b size
      variants was located in the predicted external loops of the porin. Several
      epitopes recognized by anti-Omp2b monoclonal antibodies were mapped by comparison
      of the Omp2b size variants antigenicity, and two of them were located in the most
      exposed surface loops. However, since variations are mostly driven by simple
      exchanges of conserved motifs between the two genes (except for an Omp2b version
      from an atypical strain of Brucella suis biovar 3), the porin variability does
      not result in major antigenic variability of the Brucella surface that could help
      the bacteria during the reinfection of a host. Porin variation in Brucella seems
      to result mainly in porin conductivity modifications.

PMID- 11466288
TI  - Structure-function analysis of BfpB, a secretin-like protein encoded by the
      bundle-forming-pilus operon of enteropathogenic Escherichia coli.
AB  - Production of type IV bundle-forming pili by enteropathogenic Escherichia coli
      (EPEC) requires BfpB, an outer-membrane lipoprotein and member of the secretin
      protein superfamily. BfpB was found to compose a ring-shaped, high-molecular
      weight outer-membrane complex that is stable in 4% sodium dodecyl sulfate at
      temperatures of < or = 65 degrees C. Chemical cross-linking and
      immunoprecipitation experiments disclosed that the BfpB multimeric complex
      interacts with BfpG, and mutational studies showed that BfpG is required for the
      formation and/or stability of the multimer but not for the outer-membrane
      localization of BfpB. Formation of the BfpB multimer also does not require BfpA,
      the repeating subunit of the pilus filament. Functional studies of the BfpB-BfpG
      complex revealed that its presence confers vancomycin sensitivity, indicating
      that it may form an incompletely gated channel through the outer membrane. BfpB
      expression is also associated with accumulation of EPEC proteins in growth
      medium, suggesting that it may support both pilus biogenesis and protein
      secretion.

PMID- 11466289
TI  - Conserved promoter motif is required for cell cycle timing of dnaX transcription
      in Caulobacter.
AB  - Cells use highly regulated transcriptional networks to control temporally
      regulated events. In the bacterium Caulobacter crescentus, many cellular
      processes are temporally regulated with respect to the cell cycle, and the genes
      required for these processes are expressed immediately before the products are
      needed. Genes encoding factors required for DNA replication, including dnaX,
      dnaA, dnaN, gyrB, and dnaK, are induced at the G(1)/S-phase transition. By
      analyzing mutations in the dnaX promoter, we identified a motif between the -10
      and -35 regions that is required for proper timing of gene expression. This
      motif, named RRF (for repression of replication factors), is conserved in the
      promoters of other coordinately induced replication factors. Because mutations in
      the RRF motif result in constitutive gene expression throughout the cell cycle,
      this sequence is likely to be the binding site for a cell cycle-regulated
      transcriptional repressor. Consistent with this hypothesis, Caulobacter extracts
      contain an activity that binds specifically to the RRF in vitro.

PMID- 11466290
TI  - Oxidation of phenolate siderophores by the multicopper oxidase encoded by the
      Escherichia coli yacK gene.
AB  - A gene (yacK) encoding a putative multicopper oxidase (MCO) was cloned from
      Escherichia coli, and the expressed enzyme was demonstrated to exhibit
      phenoloxidase and ferroxidase activities. The purified protein contained six
      copper atoms per polypeptide chain and displayed optical and electron
      paramagnetic resonance (EPR) spectra consistent with the presence of type 1, type
      2, and type 3 copper centers. The strong optical A(610) (E(610) = 10,890 M(-1)
      cm(-1)) and copper stoichiometry were taken as evidence that, similar to
      ceruloplasmin, the enzyme likely contains multiple type 1 copper centers. The
      addition of copper led to immediate and reversible changes in the optical and EPR
      spectra of the protein, as well as decreased thermal stability of the enzyme.
      Copper addition also stimulated both the phenoloxidase and ferroxidase activities
      of the enzyme, but the other metals tested had no effect. In the presence of
      added copper, the enzyme displayed significant activity against two of the
      phenolate siderophores utilized by E. coli for iron uptake, 2,3-dihydroxybenzoate
      and enterobactin, as well as 3-hydroxyanthranilate, an iron siderophore utilized
      by Saccharomyces cerevisiae. Oxidation of enterobactin produced a colored
      precipitate suggestive of the polymerization reactions that characterize
      microbial melanization processes. As oxidation should render the phenolate
      siderophores incapable of binding iron, yacK MCO activity could influence levels
      of free iron in the periplasm in response to copper concentration. This mechanism
      may explain, in part, how yacK MCO moderates the sensitivity of E. coli to
      copper.

PMID- 11466291
TI  - The HilA box and sequences outside it determine the magnitude of HilA-dependent
      activation of P(prgH) from Salmonella pathogenicity island 1.
AB  - Salmonella requires genes on the Salmonella pathogenicity island 1 (SPI1) for the
      intestinal phase of infection in several models of pathogenesis. In Salmonella
      enterica serovar Typhimurium, most SPI1 genes are arranged in operons that are
      coordinately regulated by the SPI1-encoded protein HilA. In the past, it has been
      shown that HilA directly activates two promoters on SPI1, P(invF-1) and P(prgH).
      P(invF-1) contains a HilA binding site, termed a HilA box, that is necessary and
      sufficient for activation by HilA. The HilA box is 17 nucleotides long and
      contains a direct repeat comprised of two hexamers separated by 5 nucleotides,
      centered at -45 relative to the start site of transcription. P(prgH) also
      contains a HilA box, and here we investigate its role at P(prgH). We have found
      that the HilA box is necessary, but not sufficient, for HilA-dependent activation
      of P(prgH). Instead, half-site-like hexamers outside the HilA box appear to be
      required for HilA-dependent activation of P(prgH), even though HilA binds to the
      HilA box in the absence of these hexamers. Thus, although HilA-dependent
      activation of P(invF-1) and P(prgH) coordinates the expression of the structural
      genes for a type III secretion apparatus and the effectors secreted by that
      apparatus, it is also possible that mechanisms not apparent under in vitro
      inducing conditions could separate the expression of invFGEABC-spaMNOPQRS-sicA
      sipBCDA-iacP-sicP-sptP and prgHIJK-orgABC.

PMID- 11466292
TI  - Genetic requirements for induction of germination of spores of Bacillus subtilis
      by Ca(2+)-dipicolinate.
AB  - Dormant Bacillus subtilis spores can be induced to germinate by nutrients, as
      well as by nonmetabolizable chemicals, such as a 1:1 chelate of Ca(2+) and
      dipicolinic acid (DPA). Nutrients bind receptors in the spore, and this binding
      triggers events in the spore core, including DPA excretion and rehydration, and
      also activates hydrolysis of the surrounding cortex through mechanisms that are
      largely unknown. As Ca(2+)-DPA does not require receptors to induce spore
      germination, we asked if this process utilizes other proteins, such as the
      putative cortex-lytic enzymes SleB and CwlJ, that are involved in nutrient
      induced germination. We found that Ca(2+)-DPA triggers germination by first
      activating CwlJ-dependent cortex hydrolysis; this mechanism is different from
      nutrient-induced germination where cortex hydrolysis is not required for the
      early germination events in the spore core. Nevertheless, since nutrients can
      induce release of the spore's DPA before cortex hydrolysis, we examined if the
      DPA excreted from the core acts as a signal to activate CwlJ in the cortex.
      Indeed, endogenous DPA is required for nutrient-induced CwlJ activation and this
      requirement was partially remedied by exogenous Ca(2+)-DPA. Our findings thus
      define a mechanism for Ca(2+)-DPA-induced germination and also provide the first
      definitive evidence for a signaling pathway that activates cortex hydrolysis in
      response to nutrients.

PMID- 11466293
TI  - Properties of spores of Bacillus subtilis blocked at an intermediate stage in
      spore germination.
AB  - Germination of mutant spores of Bacillus subtilis unable to degrade their cortex
      is accompanied by excretion of dipicolinic acid and uptake of some core water.
      However, compared to wild-type germinated spores in which the cortex has been
      degraded, the germinated mutant spores accumulated less core water, exhibited
      greatly reduced enzyme activity in the spore core, synthesized neither ATP nor
      reduced pyridine or flavin nucleotides, and had significantly higher resistance
      to heat and UV irradiation. We propose that the germinated spores in which the
      cortex has not been degraded represent an intermediate stage in spore
      germination, which we term stage I.

PMID- 11466294
TI  - Specificity and topology of the Escherichia coli xanthosine permease, a
      representative of the NHS subfamily of the major facilitator superfamily.
AB  - The specificity of XapB permease was compared with that of the known nucleoside
      transporters NupG and NupC. XapB-mediated xanthosine uptake is abolished by 2,4
      dinitrophenol and exhibits saturation kinetics with an apparent K(m) of 136
      microM. A 12-transmembrane-segment model was confirmed by translational fusions
      to alkaline phosphatase and the alpha fragment of beta-galactosidase.

PMID- 11466295
TI  - Control of a family of phosphatase regulatory genes (phr) by the alternate sigma
      factor sigma-H of Bacillus subtilis.
AB  - A family of 11 phosphatases can help to modulate the activity of response
      regulator proteins in Bacillus subtilis. Downstream of seven of the rap
      (phosphatase) genes are phr genes, encoding secreted peptides that function as
      phosphatase regulators. By using fusions to lacZ and primer extension analysis,
      we found that six of the seven phr genes are controlled by the alternate sigma
      factor sigma-H. These results expand the potential of sigma-H to contribute to
      the output of several response regulators by controlling expression of inhibitors
      of phosphatases.

PMID- 11466296
TI  - YLR209c encodes Saccharomyces cerevisiae purine nucleoside phosphorylase.
AB  - The yeast YLR209c (PNP1) gene encodes a protein highly similar to purine
      nucleoside phosphorylases. This protein specifically metabolized inosine and
      guanosine. Disruption of PNP1 led to inosine and guanosine excretion in the
      medium, thus showing that PNP1 plays an important role in the metabolism of these
      purine nucleosides in vivo.

PMID- 11466297
TI  - Autoamplification of a two-component regulatory system results in "learning"
      behavior.
AB  - We have tested the hypothesis that the autoamplification of two-component
      regulatory systems results in "learning" behavior, i.e., that bacteria respond
      faster or more extensively to a signal when a similar signal has been perceived
      in the past. Indeed, the induction of alkaline phosphatase activity upon
      phosphate limitation was faster if the cultures had been limited for phosphate
      previously, and this faster response correlated with the autoamplification of the
      cognate two-component system.

PMID- 11466298
TI  - Isolation and characterization of a Shewanella putrefaciens MR-1 electron
      transport regulator etrA mutant: reassessment of the role of EtrA.
AB  - Shewanella putrefaciens MR-1 has emerged as a good model to study anaerobic
      respiration and electron transport-linked metal reduction. Its remarkable
      respiratory plasticity suggests the potential for a complex regulatory system to
      coordinate electron acceptor use in the absence of O(2). It had previously been
      suggested that EtrA (electron transport regulator A), an analog of Fnr (fumarate
      nitrate regulator) from Escherichia coli, may regulate gene expression for
      anaerobic electron transport. An etrA knockout strain (ETRA-153) was isolated
      from MR-1 using a gene replacement strategy. Reverse transcription-PCR analysis
      of total RNA demonstrated the loss of the etrA mRNA in ETRA-153. ETRA-153 cells
      retained the ability to grow on all electron acceptors tested, including
      fumarate, trimethylamine N-oxide (TMAO), thiosulfate, dimethyl sulfoxide, ferric
      citrate, nitrate, and O(2), as well as the ability to reduce ferric citrate,
      manganese(IV), nitrate, and nitrite. EtrA is therefore not necessary for growth
      on, or the reduction of, these electron acceptors. However, ETRA-153 had reduced
      initial growth rates on fumarate and nitrate but not on TMAO. The activities for
      fumarate and nitrate reductase were lower in ETRA-153, as were the levels of
      fumarate reductase protein and transcript. ETRA-153 was also deficient in one
      type of ubiquinone. These results are in contrast to those previously reported
      for the putative etrA mutant METR-1. Molecular analysis of METR-1 indicated that
      its etrA gene is not interrupted; its reported phenotype was likely due to the
      use of inappropriate anaerobic growth conditions.

PMID- 11466299
TI  - The licC gene of Streptococcus pneumoniae encodes a CTP:phosphocholine
      cytidylyltransferase.
AB  - The licC gene product of Streptococcus pneumoniae was expressed and
      characterized. LicC is a nucleoside triphosphate transferase family member and
      possesses CTP:phosphocholine cytidylyltransferase activity. Phosphoethanolamine
      is a poor substrate. The LicC protein plays a role in the biosynthesis of the
      phosphocholine-derivatized cell wall constituents that are critical for cell
      separation and pathogenesis.

PMID- 11466300
TI  - Iron-dependent transcription of the frpB gene of Helicobacter pylori is
      controlled by the Fur repressor protein.
AB  - We have overexpressed and purified the Helicobacter pylori Fur protein and
      analyzed its interaction with the intergenic regions of divergent genes involved
      in iron uptake (frpB and ceuE) and oxygen radical detoxification (katA and tsaA).
      DNase I footprint analysis showed that Fur binds specifically to a high-affinity
      site overlapping the P(frpB) promoter and to low-affinity sites located upstream
      from promoters within both the frpB-katA and ceuE-tsaA intergenic regions.
      Construction of an isogenic fur mutant indicated that Fur regulates transcription
      from the P(frpB) promoter in response to iron. In contrast, no effect by either
      Fur or iron was observed for the other promoters.

PMID- 11466301
TI  - Localization of NAD(P)H dehydrogenase in the cyanobacterium Synechocystis sp.
      strain PCC 6803.
AB  - Antibodies raised against NdhH and NdhB detected these proteins in the thylakoid
      membrane of Synechocystis sp. strain PCC 6803, but not in a purified cytoplasmic
      membrane. We conclude that NAD(P)H dehydrogenase is largely, if not exclusively,
      confined to the thylakoid membrane.

PMID- 11466302
TI  - Expression of functional receptor-coupled TRPC3 channels in DT40 triple receptor
      InsP3 knockout cells.
AB  - The TRPC3 channel, an intensively studied member of the widely expressed
      transient receptor potential (TRP) family, is a Ca(2+)-conducting channel
      activated in response to phospholipase C-coupled receptors. Despite scrutiny, the
      receptor-induced mechanism to activate TRPC3 channels remains unclear. Evidence
      indicates TRPC3 channels interact directly with intracellular inositol 1,4,5
      trisphosphate receptors (InsP(3)Rs) and that channel activation is mediated
      through coupling to InsP(3)Rs. TRPC3 channels were expressed in DT40 chicken B
      lymphocytes in which all three InsP(3)R genes were deleted (DT40InsP(3)R-k/o).
      Endogenous B-cell receptors (BCR) coupled through Syk kinase to phospholipase C
      gamma (PLC-gamma) activated the expressed TRPC3 channels in both DT40w/t and
      DT40InsP(3)R-k/o cells. The diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-sn
      glycerol (OAG) also activated TRPC3 channels independently of InsP(3)Rs. BCR
      induced TRPC3 activation was blocked by the PLC enzymic inhibitor, U-73122, and
      also blocked by wortmannin-induced PLC substrate depletion. Neither U-73122 nor
      wortmannin modified either OAG-induced TRPC3 activation or store-operated channel
      activation in DT40 cells. Cotransfection of cells with both G protein-coupled M5
      muscarinic receptors and TRPC3 channels resulted in successful M5 coupling to
      open TRPC3 channels mediated by PLC-beta. We conclude that TRPC3 channels are
      activated independently of InsP(3)Rs through DAG production resulting from
      receptor-mediated activation of either PLC-gamma or PLC-beta.

PMID- 11466303
TI  - Modulation of ion transport by direct targeting of protein phosphatase type 1 to
      the Na-K-Cl cotransporter.
AB  - The specificity of major protein phosphatases is conferred via targeting
      subunits, each of which binds specifically to the phosphatase and targets it to
      the vicinity of substrate proteins. In the case of protein phosphatase 1 (PP1),
      an RVXFXD motif on a targeting subunit binds to a cleft in PP1c, the catalytic
      subunit. Here we report that a substrate of PP1, the Na-K-Cl cotransporter
      (NKCC1), bears this motif in its N terminus near sites of regulatory
      phosphorylation and that direct binding of PP1 to NKCC1 is functionally important
      in determining the set point for intracellular chloride regulation. NKCC1 mutants
      in which the motif is destroyed or improved exhibit dramatically shifted
      activation curves because of a change in the rate of cotransporter
      dephosphorylation. Furthermore, direct interaction of NKCC1 and PP1c observed by
      coprecipitation of the two proteins is not seen in a mutant lacking the site.
      This establishes a new paradigm of phosphatase specificity, one in which a
      substrate protein containing an RVXFXD motif binds directly to PP1c; we propose
      that this may be a quite general mechanism.

PMID- 11466304
TI  - Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR.
AB  - The orphan nuclear receptor SXR coordinately regulates drug clearance in response
      to a wide variety of xenobiotic compounds. This signaling system protects the
      body from exposure to toxic compounds; however, it can also pose a severe barrier
      to drug therapy. We now demonstrate that the human immunodeficiency virus (HIV)
      protease inhibitor ritonavir binds SXR and activates its target genes. This
      represents an example of a commonly used therapeutic agent that effectively
      activates SXR. We also show that other protease inhibitors are weaker
      (saquinavir) or unable to activate SXR (nelfinavir, indinavir) thus defining
      analogs that fail to induce SXR-regulated clearance pathways. Interestingly, HIV
      protease inhibitors are distinct from previously known SXR ligands in that they
      are peptide mimetic compounds. This expands the ligand specificity of SXR to
      include this unique chemical class whose pharmaceutical significance is
      expanding. Finally, we show that SXR ligands activate expression of multiple
      resistance protein 2, a critical regulator of bile flow and biliary drug
      excretion. These findings have important implications for the role of SXR in
      regulating drug clearance and hepatic disorders associated with impaired bile
      flow.

PMID- 11466305
TI  - Transient tyrosine phosphorylation of human ryanodine receptor upon T cell
      stimulation.
AB  - The ryanodine receptor of Jurkat T lymphocytes was phosphorylated on tyrosine
      residues upon stimulation of the cells via the T cell receptor/CD3 complex. The
      tyrosine phosphorylation was transient, reaching a maximum at 2 min, and rapidly
      declined thereafter. In co-immunoprecipitates of the ryanodine receptor, the
      tyrosine kinases p56(lck) and p59(fyn) were detected. However, only p59(fyn)
      associated with the ryanodine receptor in a stimulation-dependent fashion. Both
      tyrosine kinases, recombinantly expressed as glutathione S-transferase (GST)
      fusion proteins, phosphorylated the immunoprecipitated ryanodine receptor in
      vitro. In permeabilized Jurkat T cells, GST-p59(fyn), but not GST-p56(lck), GST
      Grb2, or GST alone, significantly and concentration-dependently enhanced Ca(2+)
      release by cyclic ADP-ribose. The tyrosine kinase inhibitor PP2 specifically
      blocked the effect of GST-p59(fyn). This indicates that intracellular Ca(2+)
      release via ryanodine receptors may be modulated by tyrosine phosphorylation
      during T cell activation.

PMID- 11466306
TI  - Indian hedgehog is an essential component of mechanotransduction complex to
      stimulate chondrocyte proliferation.
AB  - Indian hedgehog (Ihh), a member of the vertebrate hedgehog morphogen family, is a
      key signaling molecule that controls chondrocyte proliferation and
      differentiation. In this study, we show a novel function of Ihh. Namely, it acts
      as an essential mediator of mechanotransduction in cartilage. Cyclic mechanical
      stress greatly induces the expression of Ihh by chondrocytes. This induction is
      abolished by gadolinium, an inhibitor of stretch-activated channels. This
      suggests that the IHH gene is mechanoresponsive. The mechano-induction of Ihh is
      essential for stimulating chondrocyte proliferation by mechanical loading. The
      presence of an Ihh functional blocking antibody during loading completely
      abolishes the stimulatory effect of mechanical load on proliferation.
      Furthermore, Ihh mediates the mechanotransduction process in a bone morphogenic
      protein (BMP)-dependent and parathyroid hormone-related peptide-independent
      manner. BMP 2/4 are up-regulated by mechanical stress through the induction of
      Ihh, and BMP antagonist noggin inhibits mechanical stimulation of chondrocyte
      proliferation. This suggests BMP lies downstream of Ihh in mechanotransduction
      pathway. Our data suggest that Ihh may transduce mechanical signals during
      cartilage growth and repair processes.

PMID- 11466307
TI  - Role of interdomain salt bridges in the pore-forming ability of the Bacillus
      thuringiensis toxins Cry1Aa and Cry1Ac.
AB  - The four salt bridges (Asp(222)-Arg(281), Arg(233)-Glu(288), Arg(234)-Glu(274),
      and Asp(242)-Arg(265)) linking domains I and II in Cry1Aa were abolished
      individually in alpha-helix 7 mutants D222A, R233A, R234A, and D242A. Two
      additional mutants targeting the fourth salt bridge (R265A) and the double mutant
      (D242A/R265A) were rapidly degraded during trypsin activation. Mutations were
      also introduced in the corresponding Cry1Ac salt bridge (D242E, D242K, D242N, and
      D242P), but only D242N and D242P could be produced. All toxins tested, except
      D242A, were shown by light-scattering experiments to permeabilize Manduca sexta
      larval midgut brush border membrane vesicles. The three active Cry1Aa mutants at
      pH 10.5, as well as D222A at pH 7.5, demonstrated a faster rate of pore formation
      than Cry1Aa, suggesting that increases in molecular flexibility due to the
      removal of a salt bridge facilitated toxin insertion into the membrane. However,
      all mutants were considerably less toxic to M. sexta larvae than to the
      respective parental toxins, suggesting that increased flexibility made the toxins
      more susceptible to proteolysis in the insect midgut. Interdomain salt bridges,
      especially the Asp(242)-Arg(265) bridge, therefore contribute greatly to the
      stability of the protein in the larval midgut, whereas their role in intrinsic
      pore-forming ability is relatively less important.

PMID- 11466308
TI  - The cleavable N-terminal domain of plant endopolygalacturonases from clade B may
      be involved in a regulated secretion mechanism.
AB  - Polygalacturonases represent the most abundant carbohydrate hydrolase family in
      the Arabidopsis thaliana genome, and they are thought to be involved in nearly
      all of the developmental processes requiring cell wall modifications during the
      life cycle of the plant. By phylogenetic analysis, plant polygalacturonases fall
      into at least three groups, one of which is distinguished from the others by the
      presence of an additional N-terminal domain. We have used RDPG1, the
      polygalacturonase involved in pod dehiscence in oilseed rape (Brassica napus), as
      a model to investigate the function of this domain. We have confirmed that this
      domain is absent in the mature protein by determination of the N-terminal
      sequence of mature RDPG1 purified from oilseed rape pod. We have furthermore
      investigated the accumulation and subcellular localization of the precursor
      containing the N-terminal domain and of the mature protein throughout the
      development and maturation of the pod. Using recombinant expression in Pichia
      pastoris, we have produced the RDPG1 precursor, and we present evidence that the
      N-terminal domain of plant polygalacturonases is not involved in folding or
      inactivation of the precursor but may play a role in the intracellular transport
      of this protein family via a novel regulated secretion pathway.

PMID- 11466309
TI  - Anion-mediated Fe3+ release mechanism in ovotransferrin C-lobe: a structurally
      identified SO4(2-) binding site and its implications for the kinetic pathway.
AB  - The differential properties of anion-mediated Fe(3+) release between the N- and C
      lobes of transferrins have been a focus in transferrin biochemistry. The
      structural and kinetic characteristics for isolated lobe have, however, been
      documented with the N-lobe only. Here we demonstrate for the first time the
      quantitative Fe(3+) release kinetics and the anion-binding structure for the
      isolated C-lobe of ovotransferrin. In the presence of pyrophosphate, sulfate, and
      nitrilotriacetate anions, the C-lobe released Fe(3+) with a decelerated rate in a
      single exponential progress curve, and the observed first order rate constants
      displayed a hyperbolic profile as a function of the anion concentration. The
      profile was consistent with a newly derived single-pathway Fe(3+) release model
      in which the holo form is converted depending on the anion concentration into a
      "mixed ligand" intermediate that releases Fe(3+). The apo C-lobe was crystallized
      in ammonium sulfate solution, and the structure determined at 2.3 A resolution
      demonstrated the existence of a single bound SO(4)(2-) in the interdomain cleft,
      which interacts directly with Thr(461)-OG1, Tyr(431)-OH, and His(592)-NE2 and
      indirectly with Tyr(524)-OH. The latter three groups are Fe(3+)-coordinating
      ligands, strongly suggesting the facilitated Fe(3+) release upon the anion
      occupation at this site. The SO(4)(2-) binding structure supported the single
      pathway kinetic model.

PMID- 11466310
TI  - Human methionine synthase reductase, a soluble P-450 reductase-like dual
      flavoprotein, is sufficient for NADPH-dependent methionine synthase activation.
AB  - Methionine synthase is a key enzyme in the methionine cycle that catalyzes the
      transmethylation of homocysteine to methionine in a cobalamin-dependent reaction
      that utilizes methyltetrahydrofolate as a methyl group donor. Cob(I)alamin, a
      supernucleophilic form of the cofactor, is an intermediate in this reaction, and
      its reactivity renders the enzyme susceptible to oxidative inactivation. In
      bacteria, an NADPH-dependent two-protein system comprising flavodoxin reductase
      and flavodoxin, transfers electrons during reactivation of methionine synthase.
      Until recently, the physiological reducing system in mammals was unknown.
      Identification of mutations in the gene encoding a putative methionine synthase
      reductase in the cblE class of patients with an isolated functional deficiency of
      methionine synthase suggested a role for this protein in activation (Leclerc, D.,
      Wilson, A., Dumas, R., Gafuik, C., Song, D., Watkins, D., Heng, H. H. Q.,
      Rommens, J. M., Scherer, S. W., Rosenblatt, D. S., and Gravel, R. A. (1998) Proc.
      Natl. Acad. Sci. U. S. A. 95, 3059-3064). In this study, we have cloned and
      expressed the cDNA encoding human methionine synthase reductase and demonstrate
      that it is sufficient for supporting NADPH-dependent activity of methionine
      synthase at a level that is comparable with that seen in the in vitro assay that
      utilizes artificial reductants. Methionine synthase reductase is a soluble,
      monomeric protein with a molecular mass of 78 kDa. It is a member of the family
      of dual flavoproteins and is isolated with an equimolar concentration of FAD and
      FMN. Reduction by NADPH results in the formation of an air stable semiquinone
      similar to that observed with cytochrome P-450 reductase. Methionine synthase
      reductase reduces cytochrome c in an NADPH-dependent reaction at a rate (0.44
      micromol min(-1) mg(-1) at 25 degrees C) that is comparable with that reported
      for NR1, a soluble dual flavoprotein of unknown function, but is approximately
      100-fold slower than that of P-450 reductase. The K(m) for NADPH is 2.6 +/- 0.5
      microm, and the K(act) for methionine synthase reductase is 80.7 +/- 13.7 nm for
      NADPH-dependent activity of methionine synthase.

PMID- 11466311
TI  - N-terminal truncation of prion protein affects both formation and conformation of
      abnormal protease-resistant prion protein generated in vitro.
AB  - Transmissible spongiform encephalopathy diseases are characterized by conversion
      of the normal protease-sensitive host prion protein, PrP-sen, to an abnormal
      protease-resistant form, PrP-res. In the current study, deletions were introduced
      into the flexible tail of PrP-sen (23) to determine if this region was required
      for formation of PrP-res in a cell-free assay. PrP-res formation was
      significantly reduced by deletion of residues 34-94 relative to full-length
      hamster PrP. Deletion of another nineteen amino acids to residue 113 further
      reduced the amount of PrP-res formed. Furthermore, the presence of additional
      proteinase K cleavage sites indicated that deletion to residue 113 generated a
      protease-resistant product with an altered conformation. Conversion of PrP
      deletion mutants was also affected by post-translational modifications to PrP
      sen. Conversion of unglycosylated PrP-sen appeared to alter both the amount and
      the conformation of protease-resistant PrP-res produced from N-terminally
      truncated PrP-sen. The N-terminal region also affected the ability of hamster PrP
      to block mouse PrP-res formation in scrapie-infected mouse neuroblastoma cells.
      Thus, regions within the flexible N-terminal tail of PrP influenced interactions
      required for both generating and disrupting PrP-res formation.

PMID- 11466312
TI  - Cadherins mediate intercellular mechanical signaling in fibroblasts by activation
      of stretch-sensitive calcium-permeable channels.
AB  - Cells in mechanically active environments form extensive, cadherin-mediated
      intercellular junctions that are important in tissue remodeling and
      differentiation. Currently, it is unknown whether adherens junctions in
      connective tissue fibroblasts transmit mechanical signals and coordinate
      multicellular adaptations to physical forces. We hypothesized that cadherins
      mediate intercellular mechanotransduction by activating calcium-permeable,
      stretch-sensitive channels. Human gingival fibroblasts in suspension were plated
      on established homotypic monolayer cultures. The cells formed intercellular
      adherens junctions. Controlled mechanical forces were applied to intercellular
      junctions by electromagnets acting on cells containing internalized magnetite
      beads. At early but not later stages of intercellular attachment, force
      application visibly displaced magnetite bead-loaded cells and induced robust
      Ca(2+) transients (65 +/- 9.4 nm above base line). Similar Ca(2+) transients were
      induced by force application to anti-N-cadherin antibody-coated magnetite beads.
      Ca(2+) responses depended on influx of extracellular Ca(2+) through
      mechanosensitive channels because both Ca(2+) chelation and gadolinium chloride
      abolished the response and MnCl(2) quenched fura-2 fluorescence after force
      application. Force application induced accumulation of microinjected rhodamine
      actin at intercellular contacts; actin assembly was inhibited by buffering
      intracellular calcium fluxes. Our results indicate that mechanical forces applied
      to adherens junctions activate stretch-sensitive calcium-permeable channels and
      increase actin polymerization. We suggest that N-cadherins in fibroblasts are
      intercellular mechanotransducers.

PMID- 11466313
TI  - The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its
      late Golgi localization and access to beta -amyloid precursor protein (APP)
      substrate.
AB  - Release of Abeta peptides from beta-amyloid precursor protein (APP) requires
      sequential cleavage by two endopeptidases, beta- and gamma-secretases. beta
      Secretase was recently identified as a novel membrane-bound aspartyl protease,
      named BACE1, Asp2, or memapsin 2. Employing confocal microscopy and subcellular
      fractionation, we have found that BACE1 is largely situated in the distal Golgi
      membrane with a minor presence in the endoplasmic reticulum, endosomes, and
      plasma membrane in human neuroblastoma SHEP cells and in mouse Neuro-2a cell
      lines expressing either endogenous mouse BACE1 or additional exogenous human
      BACE1. The major cellular beta-secretase activity is located in the late Golgi
      apparatus, consistent with its cellular localization. Furthermore, we demonstrate
      that the single transmembrane domain of BACE1 alone determines the retention of
      BACE1 to the Golgi compartments, through examination of recombinant proteins of
      various BACE1 fragments fused to a reporter green fluorescence protein. In
      addition, we show that the transmembrane domain of BACE1 is required for the
      access of BACE1 enzymatic activity to the cellular APP substrate and hence for
      the optimal generation of the C-terminal fragment of APP (CTF99). The results
      suggest a molecular and cell biological mechanism for the regulation of beta
      secretase activity in vivo.

PMID- 11466314
TI  - 15-Deoxy-Delta 12,14-prostaglandin J2 inhibition of NF-kappaB-DNA binding through
      covalent modification of the p50 subunit.
AB  - Cyclopentenone prostaglandins display anti-inflammatory activities and interfere
      with the signaling pathway that leads to activation of transcription factor NF
      kappaB. Here we explore the possibility that the NF-kappaB subunit p50 may be a
      target for the cyclopentenone 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d
      PGJ(2)). This prostaglandin inhibited the DNA binding ability of recombinant p50
      in a dose-dependent manner. The inhibition required the cyclopentenone moiety and
      could be prevented but not reverted by glutathione and dithiothreitol. Moreover,
      a p50 mutant with a C62S mutation was resistant to inhibition, indicating that
      the effect of 15d-PGJ(2) was probably due to its interaction with cysteine 62 in
      p50. The covalent modification of p50 by 15d-PGJ(2) was demonstrated by reverse
      phase high pressure liquid chromatography and mass spectrometry analysis that
      showed an increase in retention time and in the molecular mass of 15d-PGJ(2)
      treated p50, respectively. The interaction between p50 and 15d-PGJ(2) was
      relevant in intact cells. 15d-PGJ(2) effectively inhibited cytokine-elicited NF
      kappaB activity in HeLa without reducing IkappaBalpha degradation or nuclear
      translocation of NF-kappaB subunits. 15d-PGJ(2) reduced NF-kappaB DNA binding
      activity in isolated nuclear extracts, suggesting a direct effect on NF-kappaB
      proteins. Finally, treatment of HeLa with biotinylated-15d-PGJ(2) resulted in the
      formation of a 15d-PGJ(2)-p50 adduct as demonstrated by neutravidin binding and
      immunoprecipitation. These results clearly show that p50 is a target for covalent
      modification by 15d-PGJ(2) that results in inhibition of DNA binding.

PMID- 11466315
TI  - Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo.
AB  - Histone deacetylases (HDACs) are part of transcriptional corepressor complexes
      and play key roles in regulating chromatin structure. Three different classes of
      human HDACs have been defined based on their homology to HDACs found in
      Saccharomyces cerevisiae: RPD3 (class I), HDA1 (class II), and SIR2 (class III).
      Here we describe the identification and functional characterization of HDAC7, a
      new member of the human class II HDAC family. Although HDAC7 is localized mostly
      to the cell nucleus, it is also found in the cytoplasm, suggesting
      nucleocytoplasmic shuttling. The HDAC activity of HDAC7 maps to a carboxyl
      terminal domain and is dependent on the interaction with the class I HDAC, HDAC3,
      in the cell nucleus. Cytoplasmic HDAC7 that is not bound to HDAC3 is
      enzymatically inactive. We provide evidence that the transcriptional corepressors
      SMRT and N-CoR could serve as critical mediators of HDAC7 activity by binding
      class II HDACs and HDAC3 by two distinct repressor domains. Different class II
      HDACs reside in the cell nucleus in stable and autonomous complexes with
      enzymatic activity, but the enzymatic activities associated with HDAC7 and HDAC4
      rely on shared cofactors, including HDAC3 and SMRT/N-CoR.

PMID- 11466316
TI  - Redox-dependent gating of G protein-coupled inwardly rectifying K+ channels.
AB  - G protein-coupled inwardly rectifying K(+) channels (GIRK) play a major role in
      inhibitory signaling in excitable and endocrine tissues. The gating mechanism of
      these channels is mediated by a direct interaction of the Gbetagamma subunits of
      G protein, which are released upon inhibitory neurotransmitter receptor
      activation. This gating mechanism is further manifested by intracellular factors
      such as anionic phospholipids and Na(+) and Mg(2+) ions. In addition to the
      essential role of these components for channel function, phosphorylation events
      can also modulate channel activity. In this study we explored the involvement of
      redox modulation on GIRK channel function. Extracellular application of the
      reducing agent dithiothreitol (DTT), but not reduced glutathione, activated GIRK
      channels without affecting their permeation or rectification properties. The DTT
      dependent activation was found to mimic receptor activation and to act directly
      on the channel in a membrane delimited fashion. A critical cysteine residue
      located in the N-terminal cytoplasmic domain was found to be essential for DTT
      dependent activation in hetero- and homotetrameric contexts. Interestingly, when
      mutating this cysteine residue, DTT-dependent activation was abolished, but
      receptor-mediated channel activation was not affected. These results suggest that
      intracellular redox potential can play a major role in tuning GIRK channel
      activity in a receptor-independent manner. This sort of redox modulation can be
      part of an important cellular protective mechanism against ischemic or hypoxic
      insults.

PMID- 11466317
TI  - Subunit arrangement of gamma-aminobutyric acid type A receptors.
AB  - The GABA(A) receptors are ligand-gated chloride channels. The subunit
      stoichiometry of the receptors is controversial; four, five, or six subunits per
      receptor molecule have been proposed for alphabeta receptors, whereas
      alphabetagamma receptors are assumed to be pentamers. In this study, alpha-beta
      and beta-alpha tandem cDNAs from the alpha1 and beta2 subunits of the GABA(A)
      receptor were constructed. We determined the minimal length of the linker that is
      required between the two subunits for functional channel expression for each of
      the tandem constructs. 10- and 23-amino acid residues are required for alpha-beta
      and beta-alpha, respectively. The tandem constructs either alone or in
      combination with each other failed to express functional channels in Xenopus
      oocytes. Therefore, we can exclude tetrameric or hexameric alphabeta GABA(A)
      receptors. We can also exclude proteolysis of the tandem constructs. In addition,
      the tandem constructs were combined with single alpha, beta, or gamma subunits to
      allow formation of pentameric arrangements. In contrast to the combination with
      alpha subunits, the combination with either beta or gamma subunits led to
      expression of functional channels. Therefore, a pentameric arrangement containing
      two alpha1 and three beta2 subunits is proposed for the receptor composed of
      alpha and beta subunits. Our findings also favor an arrangement
      betaalphagammabetaalpha for the receptor composed of alpha, beta, and gamma
      subunits.

PMID- 11466318
TI  - A C-terminal segment with properties of alpha-helix is essential for DNA binding
      and in vivo function of zinc finger protein Rme1p.
AB  - Rme1p plays important roles in the control of meiosis and in cell cycle
      progression through binding to upstream regions of IME1 and CLN2 in Saccharomyces
      cerevisiae. Rme1p has three zinc finger segments, and two of them are atypical.
      To determine DNA binding domain of Rme1p, a series of Rme1p derivatives fused
      with maltose-binding protein were purified and characterized by gel mobility
      shift assay. We show that not only three zinc fingers, but also the neighboring C
      terminal region is essential for DNA binding. Mutational analysis of this region
      revealed that basic residues Arg-287, Lys-290, and Arg-291 and the hydrophobic
      residues Phe-288, Leu-292, Ile-295, and Leu-296 are critical for DNA binding. In
      addition, double substitutions by proline at Asn-289 and Lys-293, each of which
      was not essential for DNA binding, abolished DNA binding. These results suggest
      that the C-terminal segment forms an amphipathic helical structure. Furthermore,
      it was shown that the mutations in the important basic residues abolish or impair
      Rme1p function in vivo for repression and inhibition of spore formation. Thus,
      the C-terminal segment is essential and acts as a novel accessory domain for DNA
      binding by zinc fingers.

PMID- 11466319
TI  - Mitogen-activated protein kinase phosphorylates and targets inducible cAMP early
      repressor to ubiquitin-mediated destruction.
AB  - Inducible cAMP early repressor (ICER) is an important mediator of cAMP
      antiproliferative activity that acts as a putative tumor suppressor gene product.
      In this study, we examined the regulation of ICER protein by phosphorylation and
      ubiquitination in human choriocarcinoma JEG-3 and mouse pituitary AtT20 cells. We
      found that cAMP stabilized ICER protein by inhibiting the mitogen-activated
      protein kinase (MAPK) cascade. Activation of the MAPK pathway increased ICER
      phosphorylation. ICER phosphorylation was abrogated by inhibition of the MAPK
      pathway either by cAMP or directly by the MAPK inhibitor PD098059. The MAPKs
      extracellular signal-regulated kinases 1 and 2 physically interact with ICER and
      mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A
      mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4
      5 h longer than its wild-type counterpart. This alteration in stability was due
      to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and
      degraded via the ubiquitin-proteasome pathway. These results present a novel cell
      signaling cross-talk mechanism at the cell nucleus between the MAPK and cAMP
      pathways, whereby MAPK targets a repressor of the cAMP-dependent gene expression
      for ubiquitination and proteasomal degradation.

PMID- 11466320
TI  - In vivo tyrosine phosphorylation sites of activated ephrin-B1 and ephB2 from
      neural tissue.
AB  - EphB2 is a receptor tyrosine kinase of the Eph family and ephrin-B1 is one of its
      transmembrane ligands. In the embryo, EphB2 and ephrin-B1 participate in neuronal
      axon guidance, neural crest cell migration, the formation of blood vessels, and
      the development of facial structures and the inner ear. Interestingly, EphB2 and
      ephrin-B1 can both signal through their cytoplasmic domains and become tyrosine
      phosphorylated when bound to each other. Tyrosine phosphorylation regulates EphB2
      signaling and likely also ephrin-B1 signaling. Embryonic retina is a tissue that
      highly expresses both ephrin-B1 and EphB2. Although the expression patterns of
      EphB2 and ephrin-B1 in the retina are different, they partially overlap, and both
      proteins are substantially tyrosine-phosphorylated. To understand the role of
      ephrin-B1 phosphorylation, we have identified three tyrosines of ephrin-B1 as in
      vivo phosphorylation sites in transfected 293 cells stimulated with soluble EphB2
      by using mass spectrometry and site-directed mutagenesis. These tyrosines are
      also physiologically phosphorylated in the embryonic retina, although the extent
      of phosphorylation at each site may differ. Furthermore, many of the tyrosines of
      EphB2 previously identified as phosphorylation sites in 293 cells (Kalo, M. S.,
      and Pasquale, E. B. (1999) Biochemistry 38, 14396-14408) are also phosphorylated
      in retinal tissue. Our data underline the complexity of ephrin-Eph bidirectional
      signaling by implicating many tyrosine phosphorylation sites of the ligand
      receptor complex.

PMID- 11466321
TI  - Agonist-dependent traffic of raft-associated Ras and Raf-1 is required for
      activation of the mitogen-activated protein kinase cascade.
AB  - Stimulation of HIRcB fibroblasts with insulin leads to accumulation of active
      components of the mitogen-activated protein kinase cascade in endocytic
      compartments. However, the factors that regulate the mobilization of these
      components through the endocytic pathway and the relevance of this event to
      cellular signaling remain unclear. Here we report that Ras proteins are
      associated with lipid rafts in resting HIRcB fibroblasts. Ras is rapidly
      internalized into the endocytic compartment following stimulation with insulin.
      The redistribution of Ras is independent of its activation. Attachment of the C
      terminal 20 amino acids of Ha-Ras to green fluorescent protein was sufficient to
      target this construct to the same loci as the endogenous Ras protein, indicating
      that Ras distribution is a consequence of the association of its lipid modified C
      terminus with membranes. Depletion of plasma membrane cholesterol delocalized Ras
      and blocked insulin-dependent Ras traffic. Cholesterol depletion also blocked
      insulin-dependent phosphorylation of MEK and mitogen-activated protein kinase
      (MAPK) but had no effects on the translocation and activation of Raf-1. A second
      inhibitor of endocytosis, cytochalasin D, also blocked insulin-dependent MAPK
      phosphorylation. Taken together, these results suggest that mobilization of
      active Raf-1 through the endocytic compartment is required for completion of the
      MAPK cascade.

PMID- 11466322
TI  - Interleukin-2 receptor beta subunit-dependent and -independent regulation of
      intestinal epithelial tight junctions.
AB  - Interleukin (IL)-15 is able to regulate tight junction formation in intestinal
      epithelial cells. However, the mechanisms that regulate the intestinal barrier
      function in response to IL-15 and the involved subunits of the IL-15 ligand
      receptor system are unknown. We determined the IL-2Rbeta subunit and IL-15
      dependent regulation of tight junction-associated proteins in the human
      intestinal epithelial cell line T-84. The IL-2Rbeta subunit was expressed and
      induced signal transduction in caveolin enriched rafts in intestinal epithelial
      cells. IL-15-mediated tightening of intestinal epithelial monolayers correlated
      with the enhanced recruitment of tight junction proteins into Triton X-100
      insoluble protein fractions. IL-15-mediated up-regulation of ZO-1 and ZO-2
      expression was independent of the IL-2Rbeta subunit, whereas the phosphorylation
      of occludin and enhanced membrane association of claudin-1 and claudin-2 by IL-15
      required the presence of the IL-2Rbeta subunit. Recruitment of claudins and
      hyperphosphorylated occludin into tight junctions resulted in a more marked
      induction of tight junction formation in intestinal epithelial cells than the up
      regulation of ZO-1 and ZO-2 by itself. The regulation of the intestinal
      epithelial barrier function by IL-15 involves IL-2Rbeta-dependent and 
      independent signaling pathways leading to the recruitment of claudins,
      hyperphosphorylated occludin, ZO-1, and ZO-2 into the tight junctional protein
      complex.

PMID- 11466323
TI  - Palmitoylation of the vasopressin V1a receptor reveals different conformational
      requirements for signaling, agonist-induced receptor phosphorylation, and
      sequestration.
AB  - In this study, we establish that the V1a vasopressin receptor (V1aR) is
      palmitoylated, and we show that this modification has an important functional
      role. Palmitoylation of the V1aR occurs within the Cys371/Cys372 couplet located
      in the proximal C-terminal tail domain. Substitution of these residues in a
      [C371G/C372G]V1aR construct effectively disrupted receptor palmitoylation. Our
      data also indicate an additional palmitoylation site at another locus in the
      receptor, as yet undefined. [3H]Palmitate incorporation was agonist-sensitive and
      increased following exposure to [Arg8]vasopressin (AVP). Given the hydrophobic
      nature of the acyl chain, palmitoylation of the C terminus of G-protein-coupled
      receptors has been proposed to form an additional intracellular loop.
      Consequently, palmitoylation/depalmitoylation will have a profound effect on the
      local conformation of this domain. The V1aR palmitoylation status regulated both
      phosphorylation and sequestration of the receptor, and furthermore,
      palmitoylation, phosphorylation, and sequestration were all regulated by AVP. The
      palmitoylation-defective construct [C371G/C372G]V1aR exhibited decreased
      phosphorylation compared to wild-type V1aR, under both basal and AVP-stimulated
      conditions, and was sequestered at a faster rate. In contrast, the binding of
      four different classes of ligand and intracellular signaling were not affected by
      palmitoylation. This study therefore establishes that there are different
      conformational requirements for signaling, agonist-induced phosphorylation, and
      sequestration of the V1aR.

PMID- 11466324
TI  - Molecular dissection of the microtubule depolymerizing activity of mitotic
      centromere-associated kinesin.
AB  - Mitotic centromere-associated kinesin (MCAK) is a microtubule depolymerizer that
      is consistent with its role in promoting chromosome segregation during mitosis.
      Here we show that the conserved motor domain of MCAK is necessary but not
      sufficient for microtubule depolymerization in cells or in vitro. The addition of
      only 30 amino acids N-terminal to the motor restores depolymerization activity.
      Furthermore, dimerization studies revealed that the smallest functional MCAK
      deletion constructs are monomers. These results define a highly conserved domain
      within MCAK and related (KIN I) kinesins that is critical for depolymerization
      activity and show that this depolymerization is not dependent on MCAK
      dimerization.

PMID- 11466326
TI  - Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory
      cells.
AB  - CD4(+)CD25(+) regulatory T cells inhibit organ-specific autoimmune diseases
      induced by CD4(+)CD25(-) T cells and are potent suppressors of CD4(+)CD25(-) T
      cell activation in vitro. We demonstrate that CD4(+)CD25(+) T cells also suppress
      both proliferation and IFN-gamma production by CD8(+) T cells induced either by
      polyclonal or Ag-specific stimuli. CD4(+)CD25(+) T cells inhibit the activation
      of CD8(+) responders by inhibiting both IL-2 production and up-regulation of IL
      2Ralpha-chain (CD25) expression. Suppression is mediated via a T-T interaction as
      activated CD4(+)CD25(+) T cells suppress the responses of TCR-transgenic CD8(+) T
      cells stimulated with soluble peptide-MHC class I tetramers in the complete
      absence of APC. These results broaden the immunoregulatory role played by
      CD4(+)CD25(+) T cells in the prevention of autoimmune diseases, but also raise
      the possibility that they may hinder the induction of effector CD8(+) T cells to
      tumor or foreign Ags.

PMID- 11466327
TI  - Cutting edge: the mouse NK cell-associated antigen recognized by DX5 monoclonal
      antibody is CD49b (alpha 2 integrin, very late antigen-2).
AB  - DX5 mAb is a useful reagent because it stains NK cells from all mouse strains
      examined. We have identified the molecule recognized by DX5 mAb by using a
      retrovirus-mediated expression cloning system. A 5-kb cDNA encoding a protein
      that is reactive with the DX5 mAb was isolated from a NK cell cDNA library, and
      this molecule was identical with CD49b (very late Ag-2, alpha(2) integrin). The
      DX5 mAb reacted with transfectants expressing CD49b, and binding of DX5 to the NK
      cells and CD49b transfectants was blocked in the presence of other anti-CD49b
      mAbs. When NK1.1(+) NK cells were cultured with IL-2, they progressively lost
      reactivity with DX5 mAb as a consequence of cellular proliferation. Cytotoxicity
      mediated by the DX5(+) NK cells was dramatically higher as compared with DX5(-)
      NK cells. Therefore, DX5 mAb recognizes CD49b and can be used to define
      functionally distinct subsets of NK cells.

PMID- 11466328
TI  - Unexpected transcriptional induction of monocyte chemoattractant protein 1 by
      proteasome inhibition: involvement of the c-Jun N-terminal kinase-activator
      protein 1 pathway.
AB  - Proteasome inhibitors, the well-known inhibitors of NF-kappaB, are recently
      considered therapeutic agents for inflammation. However, the anti-inflammatory
      properties of these agents have not been fully evaluated. In this report we
      describe a novel effect of proteasome inhibitors on the expression of monocyte
      chemoattractant protein 1 (MCP-1) in mesangial cells. We found that proteasome
      inhibitor MG132 dose-dependently induced expression of MCP-1 at the
      transcriptional level. The stimulatory effect was similarly observed with other
      proteasome inhibitors (proteasome inhibitor 1 and lactacystin) and in other cell
      types (NRK fibroblasts). The 5'-flanking region of the MCP-1 gene contains
      multiple AP-1 sites. To explore the mechanisms involved, we examined the effects
      of proteasome inhibition on the AP-1 pathway. Northern blot analysis showed that
      MG132 rapidly induced the expression of c-jun, but not c-fos. Immunoblot analysis
      showed that MG132 prevented degradation of c-Jun protein. Kinase assay revealed
      that c-Jun N-terminal kinase (JNK) was rapidly activated by MG132. Consistent
      with these results, a reporter assay showed that AP-1 activity was up-regulated
      after treatment with MG132. Curcumin, a pharmacological inhibitor of the JNK-AP-1
      pathway, abrogated the induction of MCP-1 by MG132. Similarly, stable
      transfection with a dominant-negative mutant of c-Jun attenuated both MG132
      induced activation of AP-1 and expression of MCP-1. The transcriptional
      activation by proteasome inhibitors was observed not only in MCP-1, but also in
      other AP-1-dependent genes, including stromelysin and mitogen-activated protein
      kinase phosphatase 1. These data revealed that proteasome inhibition triggered
      the expression of MCP-1 and other genes via the multistep induction of the JNK-c
      Jun/AP-1 pathway.

PMID- 11466329
TI  - Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus.
AB  - High steady-state frequencies of CMV-specific CD4(+) memory T cells are
      maintained in CMV-exposed subjects, and these cells are thought to play a key
      role in the immunologic control of this permanent infection. However, the
      essential components of this response are poorly defined. Here, we report the use
      of a step-wise application of flow cytometric and molecular techniques to
      determine the number and size of the TCR Vbeta-defined clonotypes within freshly
      obtained CMV-specific CD4(+) memory T cell populations of four healthy, CMV
      exposed human subjects. This analysis revealed a stable clonotypic hierarchy in
      which 1-3 dominant clonotypes are maintained in concert with more numerous
      subdominant and minor clonotypes. These dominant clonotypes accounted for 10-50%
      of the overall CMV response, and comprised from 0.3 to 4.0% of peripheral blood
      CD4(+) T cells. Two subjects displayed immunodominant responses to single
      epitopes within the CMV matrix phosphoprotein pp65; these single epitope
      responses were mediated by a single dominant clonotype in one subject, and by
      multiple subdominant and minor clonotypes in the other. Thus, the CMV-specific
      CD4(+) T cell memory repertoire in normal subjects is characterized by striking
      clonotypic dominance and the potential for epitope focusing, suggesting that
      primary responsibility for immunosurveillance against CMV reactivation rests with
      a handful of clones recognizing a limited array of CMV determinants. These data
      have important implications for the understanding of mechanisms by which a
      genetically stable chronic viral pathogen such as CMV is controlled, and offer
      possible insight into the failure of such control for a genetically flexible
      pathogen like HIV-1.

PMID- 11466330
TI  - CD1d-restricted NKT cells: an interstrain comparison.
AB  - CD1d-restricted Valpha14-Jalpha281 invariant alphabetaTCR(+) (NKT) cells are well
      defined in the C57BL/6 mouse strain, but they remain poorly characterized in non
      NK1.1-expressing strains. Surrogate markers for NKT cells such as
      alphabetaTCR(+)CD4(-)CD8(-) and DX5(+)CD3(+) have been used in many studies,
      although their effectiveness in defining this lineage remains to be verified.
      Here, we compare NKT cells among C57BL/6, NK1.1-congenic BALB/c, and NK1.1
      congenic nonobese diabetic mice. NKT cells were identified and compared using a
      range of approaches: NK1.1 expression, surrogate phenotypes used in previous
      studies, labeling with CD1d/alpha-galactosylceramide tetramers, and cytokine
      production. Our results demonstrate that NKT cells and their CD4/CD8-defined
      subsets are present in all three strains, and confirm that nonobese diabetic mice
      have a numerical and functional deficiency in these cells. We also highlight the
      hazards of using surrogate phenotypes, none of which accurately identify NKT
      cells, and one in particular (DX5(+)CD3(+)) actually excludes these cells.
      Finally, our results support the concept that NK1.1 expression may not be an
      ideal marker for CD1d-restricted NKT cells, many of which are NK1.1-negative,
      especially within the CD4(+) subset and particularly in NK1.1-congenic BALB/c
      mice.

PMID- 11466331
TI  - Rejection of mouse cardiac allografts by costimulation in trans.
AB  - The activation of T cells by B7 costimulation in trans has been demonstrated in
      vitro, but the in vivo relevance is unknown. To study costimulation in trans of
      CD4(+) T cells in vivo, we performed cardiac transplants from B7-1/B7-2-deficient
      mice to recipients that do not express MHC class II molecules on peripheral APCs,
      but do have functional CD4(+) T cells (II(-)/4(+) mice). This model restricts the
      B7-dependent activation of CD4(+) T cells to costimulation in trans and excludes
      any contribution from indirect Ag presentation. We find that II(-)/4(+)
      recipients reject B7-deficient grafts as rapidly as wild-type grafts, suggesting
      that costimulation in trans can mediate rejection as potently as costimulation in
      cis. Treatment of II(-)/4(+) recipients of B7-deficient grafts with depleting Abs
      to CD4 or CD8 demonstrates that indirect Ag presentation to CD8(+) cells does not
      significantly contribute to rejection. This is the first demonstration that
      costimulation in trans can mediate an immune response in vivo and has important
      therapeutic implications.

PMID- 11466332
TI  - IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded
      RNA, or lipopolysaccharide and promotes dendritic cell activation.
AB  - Cytokines that are induced by infection may contribute to the initiation of
      immune responses through their ability to stimulate dendritic cells (DCs). In
      this paper, we have addressed the role of IL-15 in DC activation, investigating
      its expression by DCs in response to three different signals of infection and
      examining its ability to stimulate DCs. We report that the expression of both IL
      15 and the IL-15 receptor alpha-chain are increased in splenic DCs from mice
      inoculated with dsRNA (poly(I:C)), LPS, or IFN-alphabeta, and in purified murine
      splenic DCs treated with IFN-alphabeta in vitro. Furthermore, IL-15 itself was
      able to activate DCs, as in vivo or in vitro exposure of splenic DCs to IL-15
      resulted in an up-regulation of costimulatory molecules, markedly increased
      production of IFN-gamma by DC and an enhanced ability of DCs to stimulate Ag
      specific CD8(+) T cell proliferation. The magnitude of all of the IL-15-induced
      changes in DCs was reduced in mice deficient for the IFN-alphabeta receptor,
      suggesting a role for IFN-alphabeta in the stimulation of DCs by IL-15. These
      results identify IL-15 as a stimulatory cytokine for DCs with the potential for
      autocrine activity and link its effects to expression of IFN-alphabeta.

PMID- 11466333
TI  - Mature dendritic cells prime functionally superior melan-A-specific CD8+
      lymphocytes as compared with nonprofessional APC.
AB  - Priming of melan-A(26/27-35)-specific CTL occurs only in a fraction of late stage
      melanoma patients, whereas during the early stages of the disease and in healthy
      volunteers, melan-A CTL have functional and phenotypic markers consistent with a
      naive phenotype. To study the requirements for expansion of naive melan-A CTL
      from healthy donors, we set up an in vitro priming protocol and, using tetramer
      assays, we demonstrate that the activity and phenotype of the expanded melan-A
      CTL are profoundly influenced by the type of APC used. Priming by nonprofessional
      APC leads to expansion of melan-A CTL with reduced cytolytic activity and low
      level of IFN-gamma secretion. In contrast, mature dendritic cells (DC) expand
      cytolytic and IFN-gamma-producing melan-A CTL. Priming by mature DC is also
      efficient at low peptide concentration and requires only one round of
      stimulation. Finally, we observed that a significant fraction of CD45RO(+) melan
      A CTL primed by mature DC expresses high levels of the homing receptor CD62L,
      whereas CTL primed by nonprofessional APC express CD62L in lower percentages and
      at lower levels. These results suggest that suboptimal priming by nonprofessional
      APC could account for the presence in vivo of dysfunctional cells and strongly
      support the immunotherapeutic use of mature DC for expansion of effector and
      memory Ag-specific CTL.

PMID- 11466334
TI  - CD44 is the physiological trigger of Fas up-regulation on rheumatoid synovial
      cells.
AB  - CD44 is a ubiquitous molecule known as a hyaluronan receptor. However, the
      relevance of CD44 to inflammatory processes, for example, rheumatoid synovitis,
      remains unclear. In this study, we propose a novel function for CD44 using
      synovial cells from rheumatoid arthritis (RA) patients and demonstrated that CD44
      cross-linking augmented Fas expression and subsequent Fas-mediated apoptosis of
      the cells: 1) cross-linking of CD44 on RA synovial cells markedly augmented Fas
      expression and its mRNA transcription; 2) engagement of CD44 up-regulated Fas on
      the cells within 3 h, much more than IL-1beta and TNF-alpha did; 3) the Fas
      mediated early apoptotic change of the cells was amplified by CD44 cross-linking;
      and 4) hyaluronan, especially when fragmented, also augmented Fas-mediated early
      apoptosis of the cells. Based on these findings, we postulate a new concept: that
      interaction of CD44 on RA synovial cells with hyaluronan fragments present in the
      surrounding extracellular matrix augments Fas expression as well as Fas-mediated
      apoptosis of synovial cells. This may lead to spontaneous growth arrest through
      Fas-Fas ligand pathway observed in synovial cells of RA synovitis in vivo.

PMID- 11466335
TI  - A novel autocrine pathway of tumor escape from immune recognition: melanoma cell
      lines produce a soluble protein that diminishes expression of the gene encoding
      the melanocyte lineage melan-A/MART-1 antigen through down-modulation of its
      promoter.
AB  - We have observed that malignant melanoma cells produce a soluble protein
      factor(s), which down-regulates melanocyte lineage Melan-A/MART-1 Ag expression
      by melanoma cells with concomitant loss of recognition by Melan-A/MART-1-specific
      T cells. This down-modulation of Melan-A/MART-1 expression, which we refer to as
      "Ag silencing," is mediated via its minimal promoter, whereas the promoter for
      the restricting Ag-presenting HLA-A2 molecule is not affected. Significantly,
      this Ag silencing is reversible, as removal of factor-containing supernatants
      from Melan-A/MART-1-expressing cells results in up-regulation of the promoter for
      the gene encoding this Ag, and renewed expression of the protein. We have
      evaluated over 20 known factors, none of which accounts for the Ag-silencing
      activity of the melanoma cell culture supernatants. The existence of this
      autocrine pathway provides an additional novel explanation for melanoma tumor
      progression in vivo in the presence of CTL specific for this melanocyte lineage
      Ag. These observations may have important implications for Melan-A/MART-1
      specific CTL-mediated immunotherapy of melanoma tumors.

PMID- 11466336
TI  - Differences in the expression of human class I MHC alleles and their associated
      peptides in the presence of proteasome inhibitors.
AB  - We have studied the contributions of proteasome inhibitor-sensitive and 
      insensitive proteases to the generation of class I MHC-associated peptides. The
      cell surface expression of 13 different human class I MHC alleles was inhibited
      by as much as 90% or as little as 40% when cells were incubated with saturating
      concentrations of three different proteasome inhibitors. Inhibitor-resistant
      class I MHC expression was not due to TAP-independent expression or preexisting
      internal stores of peptides. Furthermore, it did not correlate with the amount or
      specificity of residual proteasome activity as determined in in vitro proteolysis
      assays and was not augmented by simultaneous incubation with multiple inhibitors.
      Mass spectrometry was used to directly characterize the peptides expressed in the
      presence and absence of proteasome inhibitors. The number of peptide species
      detected correlated with the levels of class I detected by flow cytometry. Thus,
      for many alleles, a significant proportion of associated peptide species continue
      to be generated in the presence of saturating levels of proteasome inhibitors.
      Comparison of the peptide-binding motifs of inhibitor-sensitive and -resistant
      class I alleles further suggested that inhibitor-resistant proteolytic activities
      display a wide diversity of cleavage specificities, including a trypsin-like
      activity. Sequence analysis demonstrated that inhibitor-resistant peptides
      contain diverse carboxyl termini and are derived from protein substrates
      dispersed throughout the cell. The possible contributions of inhibitor-resistant
      proteasome activities and nonproteasomal proteases residing in the cytosol to the
      peptide profiles associated with many class I MHC alleles are discussed.

PMID- 11466337
TI  - A role of the mitochondrial apoptosis-inducing factor in granulysin-induced
      apoptosis.
AB  - Granulysin is a cytolytic molecule released by CTL via granule-mediated
      exocytosis. In a previous study we showed that granulysin induced apoptosis using
      both caspase- and ceramide-dependent and -independent pathways. In the present
      study we further characterize the biochemical mechanism for granulysin-induced
      apoptosis of tumor cells. Granulysin-induced death is significantly inhibited by
      Bcl-2 overexpression and is associated with a rapid (1-5 h) loss of mitochondrial
      membrane potential, which is not mediated by ceramide generation and is not
      inhibited by the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone. Ceramide generation induced by granulysin is a slow event,
      only observable at longer incubation times (12 h). Apoptosis induced by exogenous
      natural (C(18)) ceramide is truly associated with mitochondrial membrane
      potential loss, but contrary to granulysin, this event is inhibited by
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Ceramide-induced apoptosis is
      also completely prevented by Bcl-2 overexpression. The nuclear morphology of
      cells dying after granulysin treatment in the presence of caspase inhibitors
      suggested the involvement of mitochondrial apoptosis-inducing factor (AIF) in
      granulysin-induced cell death. We demonstrate using confocal microscopy that AIF
      is translocated from mitochondria to the nucleus during granulysin-induced
      apoptosis. The majority of Bcl-2 transfectants are protected from granulysin
      induced cell death, mitochondrial membrane potential loss, and AIF translocation,
      while a small percentage are not protected. In this small percentage the typical
      nuclear apoptotic morphology is delayed, being of the AIF type at 5 h time, while
      at longer times (12 h) the normal apoptotic morphology is predominant. These and
      previous results support a key role for the mitochondrial pathway of apoptosis,
      and especially for AIF, during granulysin-induced tumoral cell death.

PMID- 11466338
TI  - Il-4 influences apoptosis of mycobacterium-reactive lymphocytes in the presence
      of TNF-alpha.
AB  - T cell apoptosis is associated with defective cell-mediated effector functions in
      several infectious diseases. In tuberculosis, there is evidence that T cell
      apoptosis may be cytokine mediated, but the mechanisms are not clearly
      understood. Type 2 cytokines have recently been associated with disease extent in
      human tuberculosis, but they have not previously been linked to apoptosis in
      mycobacterium-reactive T cells. This study presents evidence that PBLs from
      healthy donors respond to sonicated Mycobacterium tuberculosis Ags with increased
      IL-4 gene activation, CD30 expression, and apoptosis. The changes were
      significantly greater than those observed when cells were stimulated with Ags
      from nonpathogenic Mycobacterium vaccae. A hypothesis linking these observations
      was tested. CD30 expression and TNF-alpha-mediated lymphocyte apoptosis were both
      down-regulated by inhibiting IL-4 in this model. TNFR-associated factor 2 (TRAF2)
      expression was down-regulated in CD30(+) cells, and addition of anti-TNF-alpha Ab
      significantly reduced apoptosis in the CD30(+) but not the CD30(-) population.
      These observations support the hypothesis that increased IL-4 expression in M.
      tuberculosis-activated lymphocytes promotes CD30 expression, which sensitizes the
      lymphocytes to TNF-alpha-mediated apoptosis via TRAF2 depletion. This may be one
      mechanism by which IL-4 is associated with immunopathological consequences in
      human tuberculosis.

PMID- 11466339
TI  - Human IL-18 receptor and ST2L are stable and selective markers for the respective
      type 1 and type 2 circulating lymphocytes.
AB  - CD4(+) (Th) and CD8(+) (Tc) T and NK lymphocytes can be divided into type 1 and 2
      subsets according to their cytokine secretion profile. Studies on the role of
      lymphocyte subsets in human diseases have been hampered by the lack of stable
      surface markers to define them. Recently, we reported that ST2L and IL-18R are
      stably expressed on murine Th2 and Th1 cells, respectively. In this study, we
      generated Abs to human homologues of ST2L and IL-18R and tested them against
      Th1/Th2, Tc1/Tc2, and NK1/NK2 lines and PBMCs from healthy individuals. We show
      for the first time that ST2L and IL-18R are stable selective cell surface markers
      for human Th2/Tc2/NK2 and Th1/Tc1/NK1 lymphocytes, respectively. We then
      investigated PBMCs from HIV-infected patients and HIV-negative individuals, to
      test whether Abs to these two surface markers could be used directly to monitor
      lymphocyte subset distribution in human diseases. We found a clear Th1 to Th2
      shift in the HIV-infected individuals, thus settling a long-standing controversy
      and include, for the first time, Tc and NK cells as well. Therefore, these cell
      surface molecules could serve as important determinants of the immune status of
      human diseases in general, and thereby could be useful for therapeutic monitoring
      and intervention.

PMID- 11466340
TI  - CD4+CD25high regulatory cells in human peripheral blood.
AB  - Thymectomy in mice on neonatal day 3 leads to the development of multiorgan
      autoimmune disease due to loss of a CD(+)CD25(+) T cell regulatory population in
      their peripheral lymphoid tissues. Here, we report the identification of a CD4(+)
      population of regulatory T cells in the circulation of humans expressing high
      levels of CD25 that exhibit in vitro characteristics identical with those of the
      CD4(+)CD25(+) regulatory cells isolated in mice. With TCR cross-linking,
      CD4(+)CD25(high) cells did not proliferate but instead totally inhibited
      proliferation and cytokine secretion by activated CD4(+)CD25(-) responder T cells
      in a contact-dependent manner. The CD4(+)CD25(high) regulatory T cells expressed
      high levels of CD45RO but not CD45RA, akin to the expression of CD45RB(low) on
      murine CD4(+)CD25(+) regulatory cells. Increasing the strength of signal by
      providing either costimulation with CD28 cross-linking or the addition of IL-2 to
      a maximal anti-CD3 stimulus resulted in a modest induction of proliferation and
      the loss of observable suppression in cocultures of CD4(+)CD25(high) regulatory
      cells and CD4(+)CD25(-) responder cells. Whereas higher ratios of
      CD4(+)CD25(high) T cells are required to suppress proliferation if the PD-L1
      receptor is blocked, regulatory cell function is shown to persist in the absence
      of the PD-1/PD-L1 or CTLA-4/B7 pathway. Thus, regulatory CD4 T cells expressing
      high levels of the IL-2 receptor are present in humans, providing the opportunity
      to determine whether alterations of these populations of T cells are involved in
      the induction of human autoimmune disorders.

PMID- 11466341
TI  - A VH12 transgenic mouse exhibits defects in pre-B cell development and is unable
      to make IgM+ B cells.
AB  - V(H)12 B cells undergo stringent selection at multiple checkpoints to favor
      development of B-1 cells that bind phosphatidylcholine. Selection begins with the
      V(H) third complementarity-determining region (CDR3) at the pre-B cell stage, in
      which most V(H)12 pre-B cells are selectively eliminated, enriching for those
      with V(H)CDR3s of 10 aa and a fourth position Gly (designated 10/G4). To
      understand this selection, we compared B cell differentiation in mice of two
      V(H)12 transgenic lines, one with the favored 10/G4 V(H)CDR3 and one with a non
      10/G4 V(H)CDR3 of 8 aa and no Gly (8/G0). Both H chains drive B cell
      differentiation to the small pre-BII cell stage, and induce allelic exclusion and
      L chain gene rearrangement. However, unlike 10/G4 pre-B cells, 8/G0 pre-B cells
      are deficient in cell division and unable to differentiate to B cells. We suggest
      that this is due to poor 8/G0 pre-B cell receptor expression and to an inability
      to form an 8/G0 B cell receptor. Our findings also suggest that V(H)12 H chains
      have evolved such that association with surrogate and conventional L chains is
      most efficient with a 10/G4 CDR3. Thus, selection for phosphatidylcholine-binding
      B-1 cells is most likely the underlying evolutionary basis for the loss of non
      10/G4 pre-B cells.

PMID- 11466342
TI  - Positive signaling through CD72 induces mitogen-activated protein kinase
      activation and synergizes with B cell receptor signals to induce X-linked
      immunodeficiency B cell proliferation.
AB  - CD72 is a 45-kDa B cell transmembrane glycoprotein that has been shown to be
      important for B cell activation. However, whether CD72 ligation induces B cell
      activation by delivering positive signals or sequestering negative signals away
      from B cell receptor (BCR) signals remains unclear. Here, by comparing the late
      signaling events associated with the mitogen-activated protein kinase pathway, we
      identified many similarities and some differences between CD72 and BCR signaling.
      Thus, CD72 and BCR activated the extracellular signal-regulated kinase (ERK) and
      the c-Jun N-terminal kinase (JNK) but not p38 mitogen-activated protein kinase.
      Both CD72- and BCR-mediated ERK and JNK activation required protein kinase C
      activity, which was equally important for CD72- and BCR-induced B cell
      proliferation. However, CD72 induced stronger JNK activation compared with BCR.
      Surprisingly, the JNK activation induced by both BCR and CD72 is Btk independent.
      Although both CD72 and BCR induced Btk-dependent ERK activation, CD72-mediated
      proliferation is more resistant to blocking of ERK activity than that of BCR, as
      shown by the proliferation response of B cells treated with PD98059 and dibutyryl
      cAMP, agents that inhibit ERK activity. Most importantly, CD72 signaling
      compensated for defective BCR signaling in X-linked immunodeficiency B cells and
      partially restored the proliferation response of X-linked immunodeficiency B
      cells to anti-IgM ligation. These results suggest that CD72 signals B cells by
      inducing BCR-independent positive signaling pathways.

PMID- 11466343
TI  - Processing of exogenous antigens for presentation by class I MHC molecules
      involves post-Golgi peptide exchange influenced by peptide-MHC complex stability
      and acidic pH.
AB  - Vacuolar alternate class I MHC (MHC-I) Ag processing allows presentation of
      exogenous Ag by MHC-I molecules with binding of antigenic peptides to post-Golgi
      MHC-I molecules. We investigated the role of previously bound peptides and their
      dissociation in generating peptide-receptive MHC-I molecules. TAP1-knockout
      macrophages were incubated overnight with an initial exogenous peptide, producing
      a large cohort of peptide-K(b) complexes that could influence subsequent peptide
      dissociation/exchange. Initial incubation with FAPGNYPAL, KVVRFDKL, or RGYVYQGL
      enhanced rather than reduced subsequent binding and presentation of a readout
      peptide (SIINFEKL or FAPGNYPAL) to T cells. Thus, K(b) molecules may be
      stabilized by an initial (stabilizing) peptide, enhancing their ability to bind
      readout peptide and implicating peptide dissociation/exchange. In contrast,
      incubation with SIINFEKL as stabilizing peptide reduced presentation of readout
      peptide. SIINFEKL-K(b) complexes were more stable than other peptide-K(b)
      complexes, which may limit their contribution to peptide exchange. Stabilizing
      peptides (FAPGNYPAL, KVVRFDKL, or RGYVYQGL) enhanced alternate MHC-I processing
      of HB101.Crl-OVA (Escherichia coli expressing an OVA fusion protein), indicating
      that alternate MHC-I Ag processing involves peptide dissociation/exchange.
      Stabilizing peptide enhanced processing of HB101.Crl-OVA more than presentation
      of exogenous OVA peptide (SIINFEKL), suggesting that peptide
      dissociation/exchange may be enhanced in the acidic phagosomal processing
      environment. Furthermore, exposure of cells to acidic pH increased subsequent
      binding and presentation of readout peptide. Thus, peptide dissociation/exchange
      contributes to alternate MHC-I Ag processing and may be influenced by both
      stability of peptide-MHC-I complexes and pH.

PMID- 11466344
TI  - Multiple paths for activation of naive CD8+ T cells: CD4-independent help.
AB  - CD8(+) CTLs play a pivotal role in immune responses against many viruses and
      tumors. Two models have been proposed. The "three-cell" model focuses on the role
      of CD4(+) T cells, proposing that help is only provided to CTLs by CD4(+) T cells
      that recognize Ag on the same APC. The sequential "two-cell" model proposes that
      CD4(+) T cells can first interact with APCs, which in turn activate naive CTLs.
      Although these models provide a general framework for the role of CD4(+) T cells
      in mediating help for CTLs, a number of issues are unresolved. We have
      investigated the induction of CTL responses using dendritic cells (DCs) to
      immunize mice against defined peptide Ags. We find that help is required for
      activation of naive CTLs when DCs are used as APCs, regardless of the origin or
      MHC class I restriction of the peptides we studied in this system. However,
      CD8(+) T cells can provide self-help if they are present at a sufficiently high
      precursor frequency. The important variable is the total number of T cells
      responding, because class II-knockout DCs pulsed with two noncompeting peptides
      are effective in priming.

PMID- 11466345
TI  - Minimal requirements for IgE-mediated regulation of surface Fc epsilon RI.
AB  - The IgE-FcepsilonRI network plays a central role in allergic inflammation. IgE
      levels control cell surface levels of FcepsilonRI and, in turn, FcepsilonRI
      levels modulate the intensity of effector responses. Treatment of allergic
      patients with anti-IgE Abs has been shown to induce a decrease in FcepsilonRI
      expression on basophils and a decrease in Ag-triggered histamine release.
      However, the mechanisms underlying IgE-mediated regulation of FcepsilonRI
      expression remain unclear. Here, we designed an in vitro model system to
      establish the minimal cellular requirements for regulation of FcepsilonRI by IgE.
      Using this system, we demonstrate that transcriptional regulation, hemopoietic
      specific factors, and signaling are not required for IgE-mediated increases in
      FcepsilonRI expression. IgE binding to the alpha-chain is the minimal requirement
      for the induction of FcepsilonRI up-regulation. The rate of up-regulation is
      independent of the baseline level of expression. The mechanism of this up
      regulation is the result of a combination of three factors: 1) stabilization of
      the receptor at the cell surface, which prevents receptor internalization and
      degradation; 2) use of a preformed pool of receptor comprising recycled and
      recently synthesized receptors; and 3) continued basal level of protein
      synthesis. It is possible that in vivo additional factors contribute to modulate
      the basic regulatory mechanism described here.

PMID- 11466346
TI  - Recombinant adenovirus coexpressing covalent peptide/MHC class II complex and B7
      1: in vitro and in vivo activation of myelin basic protein-specific T cells.
AB  - Previous studies have demonstrated that an MHC class II molecule with an
      antigenic peptide genetically fused to its beta-chain is capable of presenting
      this peptide to CD4(+) T cells. We hypothesized that covalent peptide/class II
      complex may direct the accessory molecules to exert their function specifically
      onto T cells in a TCR-guided fashion. To test this hypothesis, we generated
      several recombinant adenoviruses expressing covalent myelin basic protein
      peptide/I-A(u) complex (MBP(1-11)/I-A(u)) and the costimulatory molecule B7-1.
      Functional studies demonstrated that adenovirus-infected cells are capable of
      activating an MBP(1-11)-specific T cell hybridoma. Coexpression of the B7-1
      molecule and MBP(1-11)/I-A(u) by the same adenovirus leads to synergy in T cell
      activation elicited by virus-infected cells. Furthermore, studies in syngeneic
      mice infected with the various adenoviruses revealed that MBP(1-11)-specific T
      cells are specifically activated by the coexpression of B7-1 and MBP(1-11)/I-A(u)
      in vivo. In conclusion, the coexpression of the covalent peptide/class II complex
      and accessory molecules by the same adenovirus provides a unique strategy to
      modulate the epitope-specific T cell response in a TCR-guided fashion. This
      approach may be applicable to investigate the roles of other accessory molecules
      in the engagement of the TCR class II molecule by substituting B7-1 with other
      accessory molecules in the recombinant adenovirus.

PMID- 11466347
TI  - An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying
      factor in IL-12 induction of the functional IL-18 receptor complex.
AB  - IL-12 and IL-18 are both proinflammatory cytokines that contribute to promoting
      Th1 development and IFN-gamma expression. However, neither IL-12R nor IL-18R is
      expressed as a functional complex on most resting T cells. This study
      investigated the molecular mechanisms underlying the induction of an IL-18R
      complex in T cells. Resting T cells expressed IL-18Ralpha chains but did not
      exhibit IL-18 binding sites as detected by incubation with rIL-18 followed by
      anti-IL-18 Ab, suggesting a lack of IL-18Rbeta expression in resting T cells.
      Although they also failed to express IL-12R, stimulation with anti-CD3 plus anti
      CD28 generated IL-12R. Exposure of these cells to IL-12 led not only to up
      regulation of IL-18Ralpha expression but also to induction of IL-18R binding
      sites on both CD4(+) and CD8(+) T cells concomitant with IL-18Rbeta mRNA
      expression. The IL-18 binding site represented a functional IL-18R complex
      capable of exhibiting IL-18 responsiveness. IL-12 induction of an IL-18R complex
      and IL-18Rbeta mRNA expression was not observed in STAT4-deficient (STAT4(-/-)) T
      cells and was substantially decreased in IFN-gamma(-/-) T cells. However, the
      failure of STAT4(-/-) T cells to induce an IL-18R complex was not corrected by
      IFN-gamma. These results indicate that STAT4 and IFN-gamma play an indispensable
      role and a role as an amplifying factor, respectively, in IL-12 induction of the
      functional IL-18R complex.

PMID- 11466348
TI  - 4-1BB ligand induces cell division, sustains survival, and enhances effector
      function of CD4 and CD8 T cells with similar efficacy.
AB  - A costimulatory member of the TNFR family, 4-1BB, is expressed on activated T
      cells. Although some reports have suggested that 4-1BB is primarily involved in
      CD8 T cell activation, in this report we demonstrate that both CD4 and CD8 T
      cells respond to 4-1BB ligand (4-1BBL) with similar efficacy. CD4 and CD8 TCR
      transgenic T cells up-regulate 4-1BB, OX40, and CD27 and respond to 4-1BBL
      mediated costimulation during a primary response to peptide Ag. 4-1BBL enhanced
      proliferation, cytokine production, and CTL effector function of TCR transgenic T
      cells. To compare CD4 vs CD8 responses to 4-1BBL under similar conditions of
      antigenic stimulation, we performed MLRs with purified CD4 or CD8 responders from
      CD28(+/+) and CD28(-/-) mice. We found that CD8 T cells produced IL-2 and IFN
      gamma in a 4-1BBL-dependent manner, whereas under the same conditions the CD4 T
      cells produced IL-2 and IL-4. 4-1BBL promoted survival of CD4 and CD8 T cells,
      particularly at late stages of the MLR. CD4 and CD8 T cells both responded to
      anti-CD3 plus s4-1BBL with a similar cytokine profile as observed in the MLR. CD4
      and CD8 T cells exhibited enhanced proliferation and earlier cell division when
      stimulated with anti-CD3 plus anti-CD28 compared with anti-CD3 plus 4-1BBL, and
      both subsets responded comparably to anti-CD3 plus 4-1BBL. These data support the
      idea that CD28 plays a primary role in initial T cell expansion, whereas 4-1BB/4
      1BBL sustains both CD4 and CD8 T cell responses, as well as enhances cell
      division and T cell effector function.

PMID- 11466349
TI  - Heterogeneity of channel catfish CTL with respect to target recognition and
      cytotoxic mechanisms employed.
AB  - Two types of catfish alloantigen-dependent cytotoxic T cells were cloned from PBL
      from a fish immunized in vivo and stimulated in vitro with the allogeneic B cell
      line 3B11. Because these are the first clonal cytotoxic T cell lines derived from
      an ectothermic vertebrate, studies were undertaken to characterize their
      recognition and cytotoxic mechanisms. The first type of CTL (group I) shows
      strict alloantigen specificity, i.e., they specifically kill and proliferate only
      in response to 3B11 cells. The second type (group II) shows broad allogeneic
      specificity, i.e., they kill and proliferate in response to several different
      allogeneic cells in addition to 3B11. "Cold" target-inhibition studies suggest
      that group II CTL recognize their targets via a single receptor, because the
      killing of one allotarget can be inhibited by a different allotarget. Both types
      of catfish CTL form conjugates with and kill targets by apoptosis. Killing by Ag
      specific cytotoxic T cells (group I) was completely inhibited by treatment with
      EGTA or concanamycin A, and this killing is sensitive to PMSF inhibition,
      suggesting that killing was mediated exclusively by the secretory
      perforin/granzyme mechanism. In contrast, killing by the broadly specific T
      cytotoxic cells (group II) was only partially inhibited by either EGTA or
      concanamycin A, suggesting that these cells use a cytotoxic mechanism in addition
      to that involving perforin/granzyme. Consistent with the presumed use of a
      secretory pathway, both groups of CTL possess putative lytic granules. These
      results suggest that catfish CTL show heterogeneity with respect to target
      recognition and cytotoxic mechanisms.

PMID- 11466350
TI  - The role of p53 in regulating antiviral T cell responses.
AB  - It is now well established that viral infections can induce large expansions of
      Ag-specific CD8(+) T cells. These cells divide very rapidly with an estimated
      doubling time of approximately 6 h. When virus is cleared, the vast majority of
      these effector CD8 T cells undergo apoptosis. The remaining memory cells persist
      at constant levels and provide the basis for the accelerated recall response upon
      rechallenge. The molecular mechanisms that control the rapid proliferation and
      death of Ag-specific T cells are poorly understood. Because of its important role
      in controlling cell proliferation and death, we examined antiviral immune
      responses in p53(-/-) mice using lymphocytic choriomeningitis virus. We found
      that effector CD8 and CD4 responses were comparable but that memory levels were
      slightly higher in -/- mice compared with +/+ mice. The lack of a major
      difference in virus-specific T cell responses between +/+ and -/- mice suggests
      that p53 only plays a minor role in regulating the proliferation, apoptosis, and
      maintenance of Ag-specific T cells. Thus, it appears that the primary function of
      p53 is in controlling "illegitimate" proliferation and tumor development and not
      in regulating Ag-specific T cell responses.

PMID- 11466351
TI  - Transgenic expression of CD95 ligand on thyroid follicular cells confers immune
      privilege upon thyroid allografts.
AB  - Constitutive Fas ligand (FasL) expression by specialized cells in the body
      participates in the immune privilege status of tissues containing these cells.
      This property has been used to prevent rejection of allogeneic grafts.
      Nevertheless, the mechanism responsible for such protection has not been fully
      elucidated. Unfortunately, grafting of FasL transgenic (TG) tissues has been
      unsuccessful. We have generated TG mice expressing FasL (soluble + membrane
      bound) on thyroid follicular cells (TFC), and used them to show that ectopic FasL
      expression prevents thyroid allograft rejection. FasL expression on TFC led to
      markedly decreased anti-allogeneic, cytotoxic, and helper T lymphocyte
      activities. The alloantibody response in TG thyroid recipients was either
      completely inhibited or switched toward a T2-Ab response. Surprisingly, the
      beneficial effect of FasL on TG thyroid grafts was abolished by host CD4(+) T
      cell depletion. Host CD8(+) T cell depletion improved nontransgenic (NTG), but
      not TG graft survival. Altogether, our results suggest that FasL-induced
      tolerance is concomitant with a move away from a T1 type response, and a CD4 T
      cell-mediated regulation of the allocytotoxic T cell response. These results were
      dependent upon the level of FasL expression on TFC, in that low expression of
      FasL led to a less marked effect compared with the effect observed with high
      expression of FasL. These results provide some insight into the role of FasL in
      regulating destructive alloimmune responses in the case of whole organ grafting,
      and they have important implications for the development of FasL-based
      immunotherapy in organ transplantation.

PMID- 11466352
TI  - Enhanced proliferation and increased IFN-gamma production in T cells by signal
      transduced through TNF-related apoptosis-inducing ligand.
AB  - TNF-related apoptosis-inducing ligand (TRAIL, also called Apo2L), a novel member
      of TNF superfamily, induces apoptosis in transformed cell lines of diverse
      origin. TRAIL is expressed in most of the cells, and the expression is up
      regulated in activated T cells. Four receptors for TRAIL have been identified,
      and there is complex interplay between TRAIL and TRAIL receptors in vivo. The
      actual biological function of TRAIL/TRAIL receptor is still not clear. Growing
      evidence has demonstrated that members of TNF superfamily transduce signals after
      engagement with their receptors. Cross-linking of TRAIL by plate-bound rTRAIL
      receptor, death receptor 4-Fc fusion protein enhanced T cell proliferation and
      increased IFN-gamma production in conjunction with immobilized suboptimal anti
      CD3 stimulation in mouse splenocytes. The increase of T cell proliferation by
      death receptor 4-Fc was dose dependent, and this effect could be blocked by
      soluble rTRAIL proteins, indicating the occurrence of reverse signaling through
      TRAIL on T cell. The enhanced secretion of IFN-gamma mediated via TRAIL could be
      blocked by SB203580, a p38 mitogen-activated protein kinase-specific inhibitor.
      Thus, in addition to its role in inducing apoptosis by binding to the death
      receptors, TRAIL itself can enhance T cell proliferation after TCR engagement and
      signal the augmentation of IFN-gamma secretion via a p38-dependent pathway. This
      provides another example of reverse signaling by a member of TNF superfamily. In
      conclusion, our data suggest that TRAIL can itself transduce a reverse signal,
      and this may shed light on the biological function of TRAIL.

PMID- 11466353
TI  - A T cell clone's avidity is a function of its activation state.
AB  - At present it is unclear how Ag dose-dependent T cell functions, such as cytokine
      production, reflect TCR affinity and how the signal strength afforded by the Ag
      dose affects the kinetics of cytokine production by the individual T cell. We
      used a computer-assisted ELISPOT approach to address these issues. IFN-gamma
      release by a clonal population of CD4 T cells was monitored on a clonal
      population of APC while titrating the nominal peptide. The frequency of cytokine
      producing cells, the net per-cell output of cytokine, and the onset of cytokine
      production were each found to be functions of the signal strength. Sigmoidal dose
      response curves were seen at the clonal population level, but the activation
      thresholds for the individual T cells followed a Gaussian distribution. Moreover,
      the overall dose-response curve of the T cell clone revealed cyclic changes,
      becoming increasingly shifted toward lower Ag concentrations with the duration of
      time that elapsed since the last restimulation with Ag. Therefore, responsiveness
      to Ag ("functional avidity") is not a constant parameter of a T cell clone but a
      function of the T cell's history of last Ag encounter. The implications of such
      shifting activation thresholds are discussed for autoimmune disease.

PMID- 11466354
TI  - Cross-linking of EphB6 resulting in signal transduction and apoptosis in Jurkat
      cells.
AB  - Eph kinases are the largest family of receptor tyrosine kinases (RTK), and their
      ligands are cell surface molecules. The known functions of Eph kinases are mainly
      pattern formation in the CNS. Although several Eph kinases are expressed at high
      levels in hemopoietic cells and in the thymus, we have no knowledge of the
      functions of any Eph kinase in the immune system. In this study, we have
      demonstrated that an Eph kinase, EphB6, was expressed at high levels in Jurkat
      leukemic T cells. Co-cross-linking of EphB6 and CD3 led to an altered profile of
      lymphokine secretion along with proliferation inhibition of Jurkat cells. The
      cells subsequently underwent Fas-mediated apoptosis. Although EphB6 has no
      intrinsic kinase activity, its cross-linking triggered general protein tyrosine
      phosphorylation in Jurkat cells. EphB6 was found to associate with a number of
      molecules in the signaling pathways, notably Cbl. EphB6 cross-linking resulted in
      Cbl dephosphorylation and dissociation from Src homology 2 domain-containing
      tyrosine phosphatase-1 (SHP-1). Our results show that EphB6 has important
      functions in T cells, and it can transduce signals into the cells via proteins it
      associates with.

PMID- 11466355
TI  - H2-O inhibits presentation of bacterial superantigens, but not endogenous self
      antigens.
AB  - H2-O/HLA-DO are MHC class II accessory molecules that modulate exogenous Ag
      presentation. Most class II accessory molecules are expressed in all professional
      APC; however, H2-O is only expressed in B cells and medullary thymic epithelial
      cells. Because B cells present exogenous Ags and superantigens (SAgs), and
      medullary thymic epithelial cells are specialized APC for self Ags during
      negative selection in the thymus, we have hypothesized that H2-O might play a
      role in MHC class II-restricted SAg and self Ag presentation. In this study, we
      demonstrate that H2-O expression inhibits presentation of the bacterial SAgs
      staphylococcal enterotoxins A and B to four SAg-reactive T hybridoma cells. In
      contrast, H2-O has no effect on presentation of endogenous self Ags, as measured
      by tumorigenicity in vivo and Ag presentation to three self Ag-specific T
      hybridoma cells. Additional experiments suggest that H2-O inhibits presentation
      of exogenous Ags by both newly synthesized and recycling MHC class II molecules.
      These data suggest H2-O may have a physiological role in tolerance induction and
      SAg-mediated toxic shock.

PMID- 11466356
TI  - Antibody-independent antiviral function of memory CD4+ T cells in vivo requires
      regulatory signals from CD8+ effector T cells.
AB  - Previous studies have shown that vaccine-primed CD4(+) T cells can mediate
      accelerated clearance of respiratory virus infection. However, the relative
      contributions of Ab and CD8(+) T cells, and the mechanism of viral clearance, are
      poorly understood. Here we show that control of a Sendai virus infection by
      primed CD4(+) T cells is mediated through the production of IFN-gamma and does
      not depend on Ab. This effect is critically dependent on CD8(+) cells for the
      expansion of CD4(+) T cells in the lymph nodes and the recruitment of memory
      CD4(+) T cells to the lungs. Passive transfer of a CD8(+) T cell supernatant into
      CD8(+) T cell-depleted, hemagglutinin-neuraminidase (HN)(421-436)-immune muMT
      mice substantially restored the virus-specific memory CD4(+) response and
      enhanced viral control in the lung. Together, the data demonstrate for the first
      time that in vivo primed CD4(+) T cells have the capacity to control a
      respiratory virus infection in the lung by an Ab-independent mechanism, provided
      that CD8(+) T cell "help" in the form of soluble factor(s) is available during
      the virus infection. These studies highlight the importance of synergistic
      interactions between CD4(+) and CD8(+) T cell subsets in the generation of
      optimal antiviral immunity.

PMID- 11466357
TI  - A common pathway for dendritic cell and early B cell development.
AB  - B cells and dendritic cells (DCs) each develop from poorly described progenitor
      cells in the bone marrow (BM). Although a subset of DCs has been proposed to
      arise from lymphoid progenitors, a common developmental pathway for B cells and
      BM-derived DCs has not been clearly identified. To address this possibility, we
      performed a comprehensive analysis of DC differentiative potential among lymphoid
      and B lymphoid progenitor populations in adult mouse BM. We found that both the
      common lymphoid progenitors (CLPs), shown here and elsewhere to give rise
      exclusively to lymphocytes, and a down-stream early B-lineage precursor
      population devoid of T and NK cell precursor potential each give rise to DCs when
      exposed to the appropriate cytokines. This result contrasts with more mature B
      lineage precursors, all of which failed to give rise to detectable numbers of
      DCs. Significantly, both CLP and early B-lineage-derived DCs acquired several
      surface markers associated with functional DCs, and CLP-derived DCs readily
      induced proliferation of allogeneic CD4(+) T cells. Surprisingly, however, DC
      differentiation from both lymphoid-restricted progenitors was accompanied by up
      regulation of CD11b expression, a cell surface molecule normally restricted to
      myeloid lineage cells including putative myeloid DCs. Together, these data
      demonstrate that loss of DC developmental potential is the final step in B
      lineage commitment and thus reveals a previously unrecognized link between early
      B cell and DC ontogeny.

PMID- 11466358
TI  - Development and maintenance of a B220- memory B cell compartment.
AB  - We have recently demonstrated that a novel somatically mutated B220(-) memory B
      cell subset rapidly dominates the secondary immune response to (4-hydroxy-3
      nitrophenyl) acetyl (NP). Upon adoptive transfer with Ag, B220(+)NP(+) memory B
      cells produce large numbers of B220(-)NP(+) B cells that can rapidly
      differentiate into plasma cells. Therefore, it is not clear whether the novel
      B220(-) memory compartment is a consequence of secondary Ag challenge or whether
      it develops as a stable memory subset after initial Ag challenge. In this study,
      we demonstrate the gradual emergence of B220(-)NP(+) B cells in the spleen to
      maximal numbers 3 wk after initial Ag exposure. Like their B220(+) counterparts,
      the B220(-) B cells initially appear unmutated at days 5-7; however, the majority
      rapidly accumulate affinity increasing mutations by days 9-14 of the primary
      immune response. More extensive cell surface phenotype (GL7(-)BLA-1(-)CD24(
      )CD43(+)) argues strongly against germinal center localization and direct
      analysis in situ places a cohort of B220(-)CD11b(+)NP(+) B cells in the red pulp
      of the spleen and not in the MZs. These data provide direct evidence for the
      development of B220(-) memory B cells as a unique cellular consequence of primary
      Ag exposure. The cellular dynamics and molecular attributes of these unique
      memory B cells suggest they are distinct cellular products of the germinal center
      reaction in the primary response and are maintained long-term in the spleen and
      bone marrow.

PMID- 11466359
TI  - Sendai virus fusion protein mediates simultaneous induction of MHC class I/II
      dependent mucosal and systemic immune responses via the nasopharyngeal-associated
      lymphoreticular tissue immune system.
AB  - Nasal administration of Ags using a novel hybrid Ag delivery vehicle composed of
      envelope glycoproteins of Sendai virus on the surface of liposome membranes
      (fusogenic liposome) efficiently delivered Ags to Ag-sampling M cells in
      nasopharyngeal-associated lymphoreticular tissue. Additionally, fusogenic
      liposomes also effectively delivered the Ags into epithelial cells and
      macrophages in nasopharyngeal-associated lymphoreticular tissue and nasal
      passages. In vitro Ag presentation assays clearly showed that fusogenic liposomes
      effectively presented encapsulated Ags via the MHC class II-dependent pathway of
      epithelial cells as well as macrophages. Fusogenic liposomes also have an
      adjuvant activity against mucosal epithelial cells to enhance MHC class II
      expression. According to these high delivery and adjuvant activities of fusogenic
      liposomes, nasal immunization with OVA-encapsulated fusogenic liposomes induced
      high levels of OVA-specific CD4(+) Th1 and Th2 cell responses. Furthermore, Ag
      specific CTL responses and Ab productions were also elicited at both mucosal and
      systemic sites by nasal immunization with Ag-encapsulated fusogenic liposomes.
      These results indicate that fusogenic liposome is a versatile and effective
      system for the stimulation of Ag-specific immune responses at both mucosal and
      systemic compartments.

PMID- 11466360
TI  - Activating immunity in the liver. I. Liver dendritic cells (but not hepatocytes)
      are potent activators of IFN-gamma release by liver NKT cells.
AB  - A prominent subset of the hepatic innate immune system is alpha
      galactosylceramide (alphaGalCer)-reactive, (CD4(+) and CD4(-)CD8(-)) CD1d
      restricted NKT cells. We investigated in C57BL/6 (B6) mice which hepatic cell
      type stimulates hepatic NKT cell activation. Surface expression of CD1d but not
      CD40, CD80, or CD86 costimulator molecules was detected in hepatocytes. Pulsed in
      vitro or in vivo with alphaGalCer, hepatocytes triggered IL-4 release by liver
      NKT cells but required exogenous IL-12 to trigger IFN-gamma release by NKT cells.
      Liver dendritic cells (DC) isolated from nontreated mice showed low surface
      expression of MHC, CD1d, and CD40, CD80, or CD86 costimulator molecules that were
      strikingly up-regulated after alphaGalCer injection. Although liver CD11c(+) DC
      displayed lower CD1d surface expression than hepatocytes, they were potent
      stimulators of IFN-gamma and IL-4 release by liver NKT when pulsed with
      alphaGalCer in vitro or in vivo. Liver DC are thus potent stimulators of
      proinflammatory cytokine release by NKT cells, are activated themselves in the
      process of NKT cell activation, and express an activated phenotype after the NKT
      cell population is eliminated following alphaGalCer stimulation.

PMID- 11466361
TI  - IL-12 induction by a TH1-inducing adjuvant in vivo: dendritic cell subsets and
      regulation by IL-10.
AB  - IL-12 induction is critical for immune responses against many viruses and
      intracellular bacterial pathogens. Recent studies suggest that IL-12-secreting
      dendritic cells (DC) are potent Th1-inducing APC. However, controversy exists
      concerning the function of DC subsets. Murine studies have suggested that CD8(+)
      DC preferentially induce Th1 responses, whereas CD8(-) DC induce Th2 development;
      in this model, different DC subsets prime different responses. Alternatively, the
      propensity of DC subsets to prime a Th1 response could depend upon the type of
      initial stimulus. We used a prototypic Th1-inducing adjuvant, heat-killed
      Brucella abortus (HKBA) to assess stimulation of DC subsets, relationship between
      Ag burden and IL-12 production, and down-regulation of DC subset IL-12 production
      by IL-10. In this study, we show that DC were sole producers of IL-12, although
      most HKBA uptake was by splenic macrophages and granulocytes. More CD8(-) than
      CD8(+) DC produced IL-12 after HKBA challenge, whereas only CD8(+) DC produced IL
      12 after injection of another Th1-promoting microbial substance, soluble
      Toxoplasma gondii Ags. Studies in IL-10-deficient mice revealed that IL-10 down
      regulates frequency and duration of IL-12 production by both DC subsets. In the
      absence of IL-10, IL-12 expression is enabled in CD11c(low) cells, but not in
      macrophages or granulocytes. These findings support the concept of DC as the
      major IL-12 producers in spleens, but challenge the notion that CD8(+) and CD8(-)
      DC are destined to selectively induce Th1 or Th2 responses, respectively. Thus,
      the nature of the stimulating substance is important in determining which DC
      subsets are activated to produce IL-12.

PMID- 11466362
TI  - Cellular activation of leukocyte function-associated antigen-1 and its affinity
      are regulated at the I domain allosteric site.
AB  - The I domain of the integrin LFA-1 possesses a ligand binding interface that
      includes the metal ion-dependent adhesion site. Binding of the LFA-1 ligand, ICAM
      1 to the metal ion-dependent adhesion site is regulated by the I domain
      allosteric site (IDAS). We demonstrate here that intracellular signaling leading
      to activation of LFA-1 binding to ICAM-1 is regulated at the IDAS. Inhibitory
      mutations in or proximal to the IDAS are dominant to cytoplasmic signals that
      activate binding to ICAM-1. In addition, mutational activation at the IDAS
      greatly increases the binding of lymphocyte-expressed LFA-1 to ICAM-1 in response
      to PMA, but does not result in constitutive binding. Binding of a novel CD18
      activation epitope mAb to LFA-1 in response to soluble ICAM-1 binding was also
      blocked by inhibitory and was enhanced by activating IDAS mutations. Surface
      plasmon resonance using soluble wild-type LFA-1 and an IDAS mutant of LFA-1
      indicate that the IDAS can regulate a 6-fold change in the K(d) of ICAM-1
      binding. The K(d) of wild-type LFA-1 (1.2 x 10(-1) s(-1)) differed with that of
      the activating IDAS mutant (1.9 x 10(-2) s(-1)), but their K(a) values were
      identical (2.2 x 10(5) M(-1)s(-1)). We propose that IDAS regulates the binding of
      LFA-1 to ICAM-1 activated by intracellular signals. IDAS can control the affinity
      state of LFA-1 with concomitant I domain and CD18 conformational changes.

PMID- 11466363
TI  - Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an
      antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor
      related protein 2.
AB  - IL-1 is of utmost importance in the host response to immunological challenges. We
      identified and functionally characterized two novel IL-1 ligands termed IL-1delta
      and IL-1epsilon. Northern blot analyses show that these IL-1s are highly abundant
      in embryonic tissue and tissues containing epithelial cells (i.e., skin, lung,
      and stomach). In extension, quantitative real-time PCR revealed that of human
      skin-derived cells, only keratinocytes but not fibroblasts, endothelial cells, or
      melanocytes express IL-1delta and epsilon. Levels of keratinocyte IL-1delta are
      approximately 10-fold higher than those of IL-1epsilon. In vitro stimulation of
      keratinocytes with IL-1beta/TNF-alpha significantly up-regulates the expression
      of IL-1epsilon mRNA, and to a lesser extent of IL-1delta mRNA. In NF-kappaB
      luciferase reporter assays, we demonstrated that IL-1delta and epsilon proteins
      do not initiate a functional response via classical IL-1R pairs, which confer
      responsiveness to IL-1alpha and beta or IL-18. However, IL-1epsilon activates NF
      kappaB through the orphan IL-1R-related protein 2 (IL-1Rrp2), whereas IL-1delta,
      which shows striking homology to IL-1 receptor antagonist, specifically and
      potently inhibits this IL-1epsilon response. In lesional psoriasis skin,
      characterized by chronic cutaneous inflammation, the mRNA expression of both IL-1
      ligands as well as IL-1Rrp2 are increased relative to normal healthy skin. In
      total, IL-1delta and epsilon and IL-1Rrp2 may constitute an independent signaling
      system, analogous to IL-1alphabeta/receptor agonist and IL-1R1, that is present
      in epithelial barriers of our body and takes part in local inflammatory
      responses.

PMID- 11466364
TI  - Both TCR alpha and TCR delta chain diversity are regulated during thymic
      ontogeny.
AB  - TCRalpha and TCRdelta chains are coded by a common genetic locus using a single
      set of V gene segments (ADV segments). This article addresses the question of
      regulation of the use of the ADV segments by the TCRalpha and TCRdelta chains.
      Using both qualitative and quantitative analyses we have studied the use of 23
      ADV gene families as part of TCRalpha and TCRdelta transcripts. A number of
      previously undetected rearrangement and transcription events are described,
      indicating that the intrathymic TCRdelta repertoire is much more diverse than
      previously supposed. Repertoire analysis at several developmental time points
      allowed the description of regulated waves of ADV gene use, not only for TCRdelta
      chains, but also for TCRalpha chains, during thymic ontogeny. Control of these
      waves appears to be linked directly to the ADV segments and their local chromatin
      environment, which may change over the course of T cell differentiation.

PMID- 11466365
TI  - Genomic structure and transcriptional regulation of the early B cell gene chB1.
AB  - The avian B cell differentiation Ag chB1 is a membrane glycoprotein relative of
      the mammalian B cell differentiation Ag CD72. Unlike CD72, this C-type lectin is
      expressed in relatively high levels on immature B cells in the bursa of Fabricius
      and is down-regulated on mature B cells in the periphery. An immunoreceptor
      tyrosine-based inhibitory motif in the chB1 cytoplasmic tail suggests a potential
      regulatory role in intrabursal B cell development. To gain further insight into
      the selective expression and function of chB1, we determined the genomic
      organization of chB1 and examined the mechanism of its transcriptional
      regulation. The 8-exon chB1 gene proved to have very similar organization to that
      of mouse CD72, further supporting the idea that chB1 is a CD72 relative. As for
      mouse CD72, the chB1 promoter region lacks a TATA box but contains a conserved
      initiator element. The 131-bp region (-161 to -30) proximal to the
      transcriptional start site, which contains a potential early B cell factor
      binding site, is essential for the B lineage stage-specific transcription of
      chB1, whereas PU.1 and B cell-specific activator protein/Pax5 have been shown to
      play important roles in CD72 promoter activity and cell-type specificity. This
      analysis suggests that differences in transcriptional regulation of these
      phylogenetically related genes may determine the differences in expression
      pattern and, therefore, the function of avian chB1 and mammalian CD72 during B
      cell development.

PMID- 11466366
TI  - Dendritic cells from nonobese diabetic mice exhibit a defect in NF-kappa B
      regulation due to a hyperactive I kappa B kinase.
AB  - Insulin-dependent diabetes mellitus (IDDM) is characterized by the T cell
      mediated destruction of insulin-producing beta cells. Accordingly, APCs, such as
      macrophage, have also been shown to be important in the disease process. However,
      the role(s) of dendritic cells (DCs) that exhibit potent APC function remains
      undefined in IDDM. Here we demonstrate that DCs derived from nonobese diabetic
      (NOD) mice, a model for IDDM, are more sensitive to various forms of stimulation
      compared with those from C57BL/6 and BALB/c mice, resulting in increased IL-12
      secretion. This property is a consequence of hyperactivation of NF-kappaB, a
      transcription factor known to regulate IL-12 gene expression. Specifically, NOD
      DCs exhibit persistent hyperactivation of both IkappaB kinase and NF-kappaB in
      response to stimuli, in addition to selective degradation of IkappaBepsilon.
      Transfection of NOD DCs with a modified form of IkappaBalpha significantly
      reduced IL-12 secretion, suggesting that hyperactivation of NF-kappaB was in part
      responsible for increased IL-12 production. An enhanced capacity of NOD DCs to
      secrete IL-12 would be expected to contribute to the development of pathogenic
      Th1 (Tc1) cells during the diabetogenic response.

PMID- 11466367
TI  - The inhibitory effect of IL-1 beta on IL-6-induced alpha 2-macroglobulin
      expression is due to activation of NF-kappa B.
AB  - The cross-talk between the signal transduction of simultaneous acting cytokines
      largely determines the final impact of cytokines on their target genes. Both NF
      kappaB and STAT3 are transcription factors well known to be activated by many
      stimuli and to mediate transcriptional activation by binding to specific enhancer
      sequences. In this study, it is analyzed how IL-1beta inhibits IL-6-induced
      transcriptional activation of the alpha(2)-macroglobulin promoter. It is shown
      that IL-1beta prevents STAT3 binding to the two STAT3-responsive sites within the
      alpha(2)-macroglobulin promoter by association of IL-1beta-activated NF-kappaB to
      this region. The observation that inhibition of IL-6-induced transcriptional
      activation of this promoter by IL-1beta is reversed by cotransfection with I
      kappaBalpha provides evidence that NF-kappaB activation by IL-1beta is
      responsible for inhibition of IL-6-mediated trans activation of the alpha(2)
      macroglobulin gene. Accordingly, cotransfection of the NF-kappaB subunits p50 or
      p65 themselves inhibited activation of the alpha(2)-macroglobulin promoter by IL
      6. Introduction of point mutations in each of the two NF-kappaB sites overlapping
      the two STAT3 binding sites within the alpha(2)-macroglobulin promoter provides
      evidence that each of these two sites counteracts transcriptional activation via
      STAT3. Most interestingly, at least one functional NF-kappaB consensus site is
      essential for the IL-6-induced transcriptional activation of the alpha(2)
      macroglobulin promoter. Additional data are provided indicating that the
      activation of NF-kappaB by IL-1beta is also responsible for the inhibition of
      other IL-6-inducible genes, such as the alpha(1)-antichymotrypsin gene as well as
      the suppressor of cytokine signaling 3 gene, suggesting a more general relevance
      of this mechanism for transcriptional regulation.

PMID- 11466368
TI  - Human IFN-alpha protein engineering: the amino acid residues at positions 86 and
      90 are important for antiproliferative activity.
AB  - Human IFN-alpha is a family of structurally related proteins that exhibit a wide
      range of antiproliferative activities. To understand the structural basis for
      these different antiproliferative activities, eight recombinant human IFN-alpha
      hybrids (HY) of alpha21a/alpha2c (HY-4, HY-5) and mutants (site-directed
      mutagenesis (SDM)-1, 2 and cassette mutagenesis (CM)-1, 2, 3, and 4) have been
      expressed, purified, and characterized. The data showed that the amino acid
      region 81-95 is important for antiproliferative activity. Site-directed
      mutagenesis and cassette mutagenesis studies showed that if serine (S) 86 and
      asparagine (N) 90 were replaced by tyrosine (Y), the antiproliferative activity
      was increased. We have also observed that if Y86 was replaced by isoleucine (I),
      the antiproliferative activity was comparable. However, if Y86 was replaced by
      aspartic acid (D), lysine (K), or alanine (A), the antiproliferative activity was
      substantially decreased. Our results indicate that Y and/or I at position 86 and
      Y at position 90 are very important in antiproliferative activity of human IFN
      alpha. Circular dichroism spectra showed that the amino acid replacements at
      position 86 did not change the secondary structure. Thus the biological activity
      changes among those mutants do not appear to be due to conformational changes.
      The results also suggest that hydrophobic residue(s) at position 86 may be
      important for the interaction of the molecule with its receptor. The competitive
      binding data correlated with the antiproliferative activity. The N-terminal
      region of the molecule and the hydrophobic residues (including Y and I) on the C
      helix region at positions 86 and/or 90 are important for binding and
      antiproliferative activities of human IFN-alphas.

PMID- 11466369
TI  - Kinetic analysis of the interactions of complement receptor 2 (CR2, CD21) with
      its ligands C3d, iC3b, and the EBV glycoprotein gp350/220.
AB  - The molecular mechanisms involved in the interaction of complement receptor 2
      (CR2) with its natural ligands iC3b and C3d are still not well understood. In
      addition, studies regarding the binding site(s) of the receptor on C3 as well as
      the affinities of the C3 fragments for CR2 have produced contradictory results.
      In the present study, we have used surface plasmon resonance technology to study
      the interaction of CR2 with its ligands C3d, iC3b, and the EBV surface
      glycoprotein gp350/220. We measured the kinetics of binding of the receptor to
      its ligands, examined the influence of ionic contacts on these interactions, and
      assessed whether immobilized and soluble iC3b bound with similar kinetics to CR2.
      Our results indicate that 1) gp350 binding to CR2 follows a simple 1:1
      interaction, whereas that of the C3 fragments is more complex and involves more
      than one intramolecular component; 2) kinetic differences exist between the
      binding of C3d and iC3b to CR2, which may be due to an additional binding site
      found on the C3c region of iC3b; and 3) iC3b binds to CR2 with different
      kinetics, depending on whether the iC3b is in solution or immobilized on the
      surface. These findings suggest that binding of CR2 to iC3b and C3d is more
      complex than previously thought.

PMID- 11466370
TI  - C1 inhibitor: analysis of the role of amino acid residues within the reactive
      center loop in target protease recognition.
AB  - Previous analysis of a naturally occurring C1 inhibitor P2 mutant (Ala(443)-
      >Val) indicated a role for P2 in specificity determination. To define this role
      and that of other reactive center loop residues, a number of different amino
      acids were introduced at P2, as well as at P6 (Ala(439)) and P8'/9'
      (Gln(452)Gln(453)). Ala(439)-->Val is a naturally occurring mutant observed in a
      patient with hereditary angioedema. Previous data suggested that Gln(452)Gln(453)
      might be a contact site for C1s. Reactivity of the inhibitors toward target (C1s,
      C1r, kallikrein, beta factor XIIa, and plasmin) and nontarget proteases (alpha
      thrombin and trypsin) were studied. Substitution of P2 with bulky or charged
      residues resulted in decreased reactivity with all target proteases. Substitution
      with residues with hydrophobic or polar side chains resulted in decreased
      reactivity with some proteases, but in unaltered or increased reactivity with
      others. Second order rate constants for the reaction with C1s were determined for
      the mutants with activities most similar to the wild-type protein. The three P2
      mutants showed reductions in rate from 3.35 x 10(5) M(-1)s(-1) for the wild type
      to 1.61, 1.29, and 0.63 x 10(5) for the Ser, Thr, and Val mutants, respectively.
      In contrast, the Ala(439)-->Val and the Gln(452)Gln(453)-->Ala mutants showed
      little difference in association rates with C1s, in comparison with the wild-type
      inhibitor. The data confirm the importance of P2 in specificity determination.
      However, the P6 position appears to be of little, if any, importance.
      Furthermore, it appears unlikely that Gln(452)Gln(453) comprise a portion of a
      protease contact site within the inhibitor.

PMID- 11466371
TI  - Functional roles of TAP and tapasin in the assembly of M3-N-formylated peptide
      complexes.
AB  - H2-M3 is a MHC class Ib molecule with a high propensity to bind N-formylated
      peptides. Due to the paucity of endogenous Ag, the majority of M3 is retained in
      the endoplasmic reticulum (ER). Upon addition of exogenous N-formylated peptides,
      M3 trafficks rapidly to the cell surface. To understand the mechanism underlying
      Ag presentation by M3, we examined the role of molecular chaperones in M3
      assembly, particularly TAP and tapasin. M3-specific CTLs fail to recognize cells
      isolated from both TAP-deficient (TAP(o)) and tapasin-deficient mice, suggesting
      that TAP and tapasin are required for M3-restricted Ag presentation. Impaired M3
      expression in TAP(o) mice is due to instability of the intracellular pool of M3.
      Addition of N-formylated peptides to TAP(o) cells stabilizes M3 in the ER and
      partially restores surface expression. Surprisingly, significant amounts of M3
      are retained in the ER in tapasin-deficient mice, even in the presence of N
      formylated peptides. Our results define the role of TAP and tapasin in the
      assembly of M3-peptide complexes. TAP is essential for stabilization of M3 in the
      ER, whereas tapasin is critical for loading of N-formylated peptides onto the
      intracellular pool of M3. However, neither TAP nor tapasin is required for ER
      retention of empty M3.

PMID- 11466372
TI  - The murine cytomegalovirus pp89 immunodominant H-2Ld epitope is generated and
      translocated into the endoplasmic reticulum as an 11-mer precursor peptide.
AB  - The 20S proteasome is involved in the processing of MHC class I-presented Ags. A
      number of epitopes is known to be generated as precursor peptides requiring
      trimming either before or after translocation into the endoplasmic reticulum
      (ER). In this study, we have followed the proteasomal processing and TAP
      dependent ER translocation of the immunodominant epitope of the murine CMV
      immediate early protein pp89. For the first time, we experimentally linked
      peptide generation by the proteasome system and TAP-dependent ER translocation.
      Our experiments show that the proteasome generates both an N-terminally extended
      11-mer precursor peptide as well as the correct H2-L(d) 9-mer epitope, a process
      that is accelerated in the presence of PA28. Our direct peptide translocation
      assays, however, demonstrate that only the 11-mer precursor peptide is
      transported into the ER by TAPs, whereas the epitope itself is not translocated.
      In consequence, our combined proteasome/TAP assays show that the 11-mer precursor
      is the immunorelevant peptide product that requires N-terminal trimming in the ER
      for MHC class I binding.

PMID- 11466373
TI  - Differential regulation of mouse germline Ig gamma 1 and epsilon promoters by IL
      4 and CD40.
AB  - Before Ig class switching, RNA transcription through the specific S regions
      undergoing recombination is induced by cytokines and other activators that induce
      and direct switching. The resulting germline (GL) transcripts are essential for
      switch recombination. To understand the differential regulation of mouse IgG1 and
      IgE, we compared the promoters for GL gamma1 and epsilon transcripts. We
      addressed the question of why the promoter that regulates GL epsilon
      transcription is more responsive to IL-4 than the gamma1 promoter and also why GL
      epsilon transcription is more dependent on IL-4 than is gamma1 transcription. We
      found that the IL-4-responsive region of the GL epsilon promoter is more
      inducible than that of the gamma1 promoter, although each promoter contains a
      binding site for the IL-4-inducible transcription factor Stat6, located
      immediately adjacent to a binding site for a basic region leucine zipper (bZip)
      family protein. However, the arrangement and sequences of the sites differ
      between the epsilon and gamma1 promoters. The GL epsilon promoter binds Stat6
      with a 10-fold higher affinity than does the gamma1 promoter. Furthermore, the
      bZip elements of the two promoters bind different transcription factors, as the
      GL epsilon promoter binds and is activated by AP-1, whereas the gamma1 promoter
      binds and is activated by activating transcription factor 2. C/EBPbeta and
      C/EBPgamma also bind the gamma1 bZip element, although they inhibit rather than
      activate transcription. However, inhibition of promoter activity by C/EBPbeta
      does not require the bZip element and may instead occur via inhibiting the
      activity of NF-kappaB.

PMID- 11466374
TI  - Blocking the receptor for IL-10 improves antimycobacterial chemotherapy and
      vaccination.
AB  - Novel approaches are required for the prevention and therapy of mycobacterial
      infections since the only vaccine in use, bacillus Calmette-Guerin, is poorly
      effective and chemotherapy is long and often ineffective in sterilizing the
      infection. We used a mouse model of Mycobacterium avium infection to address the
      usefulness of a mAb able to block IL-10R both in treatment of primary infections
      and in conventional multidrug therapy and subunit vaccination. Treatment of
      infected mice with this mAb during the entire period of experimental infection
      had little impact on the course of M. avium infection, with a slight improvement
      in the resistance of infected mice observed in the liver and spleen at day 30 of
      infection, which was associated with increased macrophage activation and priming
      of CD4(+) T cells for IFN-gamma production. Administration of this mAb later in
      infection had no effect on its course, but improved the effectiveness of
      chemotherapy when the latter was started in a chronic phase of infection. Also,
      the anti-IL-10R mAb acted as an adjuvant in the induction of protective immunity
      upon vaccination with a mycobacterial subunit preparation.

PMID- 11466375
TI  - Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.
AB  - Certain microbial substances, e.g., LPS, can activate neutrophils or prime them
      to enhance their response to other activating agents, e.g., fMLP. We investigated
      the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation
      of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes
      characteristic of neutrophil activation, including down-regulation of CD62 ligand
      (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In
      addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the
      subsequent oxidative burst in response to fMLP as assessed by oxidation of
      dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these
      effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif
      failed to induce any priming or activation response. Although the effects of LPS
      required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein
      occurred independently of serum factors, suggesting the involvement of different
      receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB
      19-kDa lipoprotein serves as a pathogen-associated molecular pattern that
      promotes neutrophil priming and activation.

PMID- 11466376
TI  - Complement is essential for protection by an IgM and an IgG3 monoclonal antibody
      against experimental, hematogenously disseminated candidiasis.
AB  - The incidence of life-threatening, hematogenously disseminated candidiasis, which
      is predominantly caused by Candida albicans, parallels the use of modern medical
      procedures that adversely affect the immune system. Limited antifungal drug
      choices and emergence of drug-resistant C. albicans strains indicate the need for
      novel prevention and therapeutic strategies. We are developing vaccines and Abs
      that enhance resistance against experimental candidiasis. However, the prevalence
      of serum anti-Candida Abs in candidiasis patients has led to the misconception
      that Abs are not protective. To explain the apparent discrepancy between such
      clinical observations and our work, we compared functional activities of C.
      albicans-specific protective and nonprotective mAbs. Both kinds of Abs are
      agglutinins that fix complement and are specific for cell surface mannan, but the
      protective Abs recognize beta-mannan, and the nonprotective Ab is specific for
      alpha-mannan. By several indirect and direct measures, the protective mAbs more
      efficiently bind complement factor C3 to the yeast cell than do nonprotective Ab.
      We hypothesize that the C3 deposition causes preferential association of blood
      borne fungi with host phagocytic cells that are capable of killing the fungus. We
      conclude from these results that the protective potential of Abs is dependent on
      epitope specificity, serum titer, and ability to rapidly and efficiently fix
      complement to the fungal surface. The mechanism of protection appears to be
      associated with enhanced phagocytosis and killing of the fungus.

PMID- 11466377
TI  - DNA fusion vaccine designed to induce cytotoxic T cell responses against defined
      peptide motifs: implications for cancer vaccines.
AB  - DNA vaccination offers a strategy to induce immune attack on cancer cells, but
      tumor Ags are often weak. Inclusion of a "foreign" protein increases
      immunogenicity, and we found previously that fusion of the fragment C (FrC) of
      tetanus toxin to the tumor Ag sequence promotes Ab and CD4(+) responses against B
      cell tumors. For CTL responses, use of the full two-domain FrC may be less
      helpful, because known immunogenic MHC class I-binding peptides in the second
      domain could compete with attached tumor-derived epitopes. Therefore, we removed
      the second domain, retaining the N-terminal domain, which contains a "universal"
      helper epitope. We investigated the ability to induce CTL responses of candidate
      peptides placed at the C terminus of this domain. As test peptides, we
      repositioned the two known CTL motifs from the second domain to this site. Strong
      CTL responses to each peptide were induced by the engineered construct, as
      compared with the native FrC construct. Induced CTLs were able to specifically
      kill tumor cells transfected with FrC as a surrogate tumor Ag both in vitro and
      in vivo. Further reduction of the domain to a short helper epitope generated only
      weak CTL responses against fused peptides, and synthetic peptides mixed with the
      plasmid containing the first domain were ineffective. The single FrC domain
      peptide vaccine design also was able to induce high levels of CTLs against a
      known epitope from carcinoembryonic Ag. Response to peptide was suppressed if two
      FrC domains were present, consistent with immunodominance. These principles and
      designs may have relevance for cancer vaccines delivered via DNA.

PMID- 11466378
TI  - Virally infected hepatocytes are resistant to perforin-dependent CTL effector
      mechanisms.
AB  - Cell-mediated cytotoxicity plays an important role in the clearance of
      noncytopathic viruses from infected tissues. Perforin-dependent cytotoxic
      mechanisms have been noted to play an important role in the clearance of
      infections from multiple extrahepatic organs. In contrast, mice with defects in
      the Fas/Fas ligand (FasL)-mediated cytotoxicity pathway exhibit delayed clearance
      of adenovirus from the liver without apparent delay in the clearance of viral
      infections from extrahepatic organs. The present studies examined the role of
      cytotoxic effector mechanisms in intrahepatic immune responses to a replication
      defective, recombinant beta-galactosidase-encoding adenovirus (AdCMV-lacZ).
      Delayed clearance of AdCMV-lacZ from the livers of FasL-defective B6.gld mice,
      but not perforin-deficient B6.pfp(-/-) mice, was noted despite no significant
      differences in initial hepatic CD8(+) T cell IFN-gamma or TNF responses or in
      activation of intrahepatic cytotoxic lymphocytes cells capable of killing AdCMV
      lacZ-infected fibroblast targets. In contrast, AdCMV-lacZ-infected hepatocyte
      targets were far more sensitive to killing by intrahepatic cytotoxic lymphocytes
      from B6.pfp(-/-) than from B6.gld mice, and residual levels of virus-specific
      killing of hepatocyte targets by FasL-defective B6.gld CTL were blocked by TNF
      inhibition. These results suggest that inherent resistance of hepatocytes to
      cytotoxicity mediated by perforin-dependent mechanisms leaves Fas/FasL-dependent,
      cell-mediated cytotoxicity as the major pathway for CTL-mediated killing of
      virally infected hepatocytes and accounts for the more prominent role of perforin
      independent anti-viral mechanisms in immune responses in the liver.

PMID- 11466379
TI  - Impaired T cell immunity in B cell-deficient mice following viral central nervous
      system infection.
AB  - CD8(+) T cells are required to control acute viral replication in the CNS
      following infection with neurotropic coronavirus. By contrast, studies in B cell
      deficient (muMT) mice revealed Abs as key effectors in suppressing virus
      recrudescence. The apparent loss of initial T cell-mediated immune control in the
      absence of B cells was investigated by comparing T cell populations in CNS
      mononuclear cells from infected muMT and wild-type mice. Following viral
      recrudescence in muMT mice, total CD8(+) T cell numbers were similar to those of
      wild-type mice that had cleared infectious virus; however, virus-specific T cells
      were reduced at least 3-fold by class I tetramer and IFN-gamma ELISPOT analysis.
      Although overall T cell recruitment into the CNS of muMT mice was not impaired,
      discrepancies in frequencies of virus-specific CD8(+) T cells were most severe
      during acute infection. Impaired ex vivo cytolytic activity of muMT CNS
      mononuclear cells, concomitant with reduced frequencies, implicated IFN-gamma as
      the primary anti viral factor early in infection. Reduced virus-specific CD8(+) T
      cell responses in the CNS coincided with poor peripheral expansion and diminished
      CD4(+) T cell help. Thus, in addition to the lack of Ab, limited CD8(+) and
      CD4(+) T cell responses in muMT mice contribute to the ultimate loss of control
      of CNS infection. Using a model of virus infection restricted to the CNS, the
      results provide novel evidence for a role of B cells in regulating T cell
      expansion and differentiation into effector cells.

PMID- 11466380
TI  - Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against
      HIV at systemic and mucosal sites.
AB  - Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen
      associated molecular patterns that are potent stimulators of innate immunity. We
      tested the ability of ISS to act as an immunostimulatory pathogen-associated
      molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag.
      Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120
      specific immune responses which included: 1) Ab production; 2) a Th1-biased
      cytokine response; 3) the secretion of beta-chemokines, which are known to
      inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune
      responses; and 6) CD8 T cell responses that were independent of CD4 T cell help.
      Based on these results, ISS-based immunization holds promise for the development
      of an effective preventive and therapeutic HIV vaccine.

PMID- 11466381
TI  - Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals
      a critical role for NF-kappa B in leukocyte recruitment.
AB  - NF-kappaB binding sites are present in the promoter regions of many acute phase
      and inflammatory response genes, suggesting that NF-kappaB plays an important
      role in the initiation of innate immune responses. However, targeted mutations of
      the various NF-kappaB family members have yet to identify members responsible for
      this critical role. RelA-deficient mice die on embryonic day 15 from TNF-alpha
      induced liver degeneration. To investigate the importance of RelA in innate
      immunity, we genetically suppressed this embryonic lethality by breeding the RelA
      deficiency onto a TNFR type 1 (TNFR1)-deficient background. TNFR1/RelA-deficient
      mice were born healthy, but were susceptible to bacterial infections and
      bacteremia and died within a few weeks after birth. Hemopoiesis was intact in
      TNFR1/RelA-deficient newborns, but neutrophil emigration to alveoli during LPS
      induced pneumonia was severely reduced relative to that in wild-type or TNFR1
      deficient mice. In contrast, radiation chimeras reconstituted with RelA or
      TNFR1/RelA-deficient hemopoietic cells were healthy and demonstrated no defect in
      neutrophil emigration during LPS-induced pneumonia. Analysis of RNA harvested
      from the lungs of mice 4 h after LPS insufflation revealed that the induction of
      several genes important for neutrophil recruitment to the lung was significantly
      reduced in TNFR1/RelA-deficient mice relative to that in wild-type or TNFR1
      deficient mice. These results suggest that TNFR1-independent activation of RelA
      is essential in cells of nonhemopoietic origin during the initiation of an innate
      immune response.

PMID- 11466382
TI  - Essential role of neutrophils in the initiation and progression of a murine model
      of rheumatoid arthritis.
AB  - Neutrophils are prominent participants in the joint inflammation of human
      rheumatoid arthritis (RA) patients, but the extent of their role in the inductive
      phase of joint inflammation is unknown. In the K/BxN mouse RA model, transfer of
      autoreactive Ig from the K/BxN mouse into mice induces a rapid and profound joint
      specific inflammatory response reminiscent of human RA. We observed that after
      K/BxN serum transfer, the earliest clinical signs of inflammation in the ankle
      joint correlated with the presence of neutrophils in the synovial regions of
      recipient mouse ankle joints. In this study, we investigated the role of
      neutrophils in the early inflammatory response to transferred arthritogenic serum
      from the K/BxN transgenic mouse. Mice were treated with a neutrophil-depleting
      mAb before and following transfer of arthritogenic serum and scored for clinical
      indications of inflammation and severity of swelling in ankle joints and front
      paws. In the absence of neutrophils, mice were completely resistant to the
      inflammatory effects of K/BxN serum. Importantly, depletion of neutrophils in
      diseased recipient mice up to 5 days after serum transfer reversed the
      inflammatory reaction in the joints. Transfer of serum into mice deficient in the
      generation of nitrogen or oxygen radicals (inducible NO synthase 2 or gp91(phox)
      genes, respectively) gave normal inflammatory responses, indicating that neither
      pathway is essential for disease induction. These studies have identified a
      critical role for neutrophils in initiating and maintaining inflammatory
      processes in the joint.

PMID- 11466383
TI  - Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal
      epithelial cell protection against dysregulated proinflammatory gene expression
      in response to bacterial lipopolysaccharide.
AB  - The lumenal surface of the colonic epithelium is continually exposed to Gram
      negative commensal bacteria and LPS. Recognition of LPS by Toll-like receptor
      (TLR)-4 results in proinflammatory gene expression in diverse cell types.
      Normally, however, commensal bacteria and their components do not elicit an
      inflammatory response from intestinal epithelial cells (IEC). The aim of this
      study is to understand the molecular mechanisms by which IEC limit chronic
      activation in the presence of LPS. Three IEC lines (Caco-2, T84, HT-29) were
      tested for their ability to activate an NF-kappaB reporter gene in response to
      purified, protein-free LPS. No IEC line responded to LPS, whereas human dermal
      microvessel endothelial cells (HMEC) did respond to LPS. IEC responded vigorously
      to IL-1beta in this assay, demonstrating that the IL-1 receptor signaling pathway
      shared by TLRs was intact. To determine the reason for LPS hyporesponsiveness in
      IEC, we examined the expression of TLR4 and MD-2, a critical coreceptor for TLR4
      signaling. IEC expressed low levels of TLR4 compared with HMEC and none expressed
      MD-2. To determine whether the low level of TLR4 expression or absent MD-2 was
      responsible for the LPS signaling defect in IEC, the TLR4 or MD-2 gene was
      transiently expressed in IEC lines. Transient transfection of either gene
      individually was not sufficient to restore LPS signaling, but cotransfection of
      TLR4 and MD-2 in IEC led to synergistic activation of NF-kappaB and IL-8 reporter
      genes in response to LPS. We conclude that IEC limit dysregulated LPS signaling
      by down-regulating expression of MD-2 and TLR4. The remainder of the
      intracellular LPS signaling pathway is functionally intact.

PMID- 11466384
TI  - The cytoplasmic domain of L-selectin participates in regulating L-selectin
      endoproteolysis.
AB  - Neutrophil recruitment at sites of inflammation is regulated by a series of
      adhesion and activation events. L-selectin (CD62L) is a leukocyte expressed
      adhesion protein that is important for neutrophil accumulation and rolling along
      the vascular endothelium. L-selectin is unique from other adhesion molecules
      involved in leukocyte transmigration in that its adhesiveness appears to be
      regulated partly by rapid endoproteolysis. Cleavage of L-selectin occurs within a
      membrane-proximal region that results in ectodomain shedding and retention of a 6
      kDa transmembrane fragment. The cleavage domain of L-selectin has been well
      characterized through mutational analysis. Whether the cytoplasmic domain of L
      selectin also plays a role in regulating shedding is controversial. We have
      previously shown that the Ca(2+)-sensing protein calmodulin (CaM) constitutively
      associates with the cytoplasmic domain of L-selectin in transfected cell lines.
      However, in the absence of mapping and mutational analysis of the CaM-binding
      region of L-selectin, there remains no direct evidence that this interaction
      affects shedding. Using synthesized peptides and expressed L-selectin constructs,
      we demonstrate that CaM binding activity occurs in the membrane-proximal region
      of the cytoplasmic domain. Mutations engineered in this region that prevent CaM
      binding increase the proteolytic turnover of L-selectin. Moreover, we demonstrate
      that CaM binding to the 6-kDa transmembrane fragment is greatly reduced compared
      with intact L-selectin in neutrophils, suggesting that CaM binding is regulated.
      These data imply that the cytoplasmic domain of L-selectin can regulate shedding
      by a mechanism in which bound CaM may operate as a negative effector.

PMID- 11466385
TI  - The essential role of lipopolysaccharide-binding protein in protection of mice
      against a peritoneal Salmonella infection involves the rapid induction of an
      inflammatory response.
AB  - Acute and chronic hyperinflammation are of major clinical concern, and many
      treatment strategies are therefore directed to inactivating parts of the
      inflammatory system. However, survival depends on responding quickly to pathogen
      attack, and since the adaptive immune system requires several days to adequately
      react, we rely initially on a range of innate defenses, many of which operate by
      activating parts of the inflammatory network. For example, LPS-binding protein
      (LBP) can transfer the LPS of Gram-negative bacteria to CD14 on the surface of
      macrophages, and this initiates an inflammatory reaction. However, the importance
      of this chain of events in infection is unclear. First, the innate system is
      redundant, and bacteria have many components that may serve as targets for it.
      Second, LBP can transfer LPS to other acceptors that do not induce inflammation.
      In this study, we show that innate defense against a lethal peritoneal infection
      with Salmonella requires a direct proinflammatory involvement of LBP, and that
      this is a major nonredundant function of LBP in this infection model. This
      emphasizes that blocking the LBP-initiated inflammatory cascade disables an
      essential defense pathway. Any anti-inflammatory protection that may be achieved
      must be balanced against the risks inherent in blinding the innate system to the
      presence of Gram-negative pathogens.

PMID- 11466386
TI  - Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is
      associated with minimal activation of p38 mitogen-activated protein kinase.
AB  - We have investigated possible factors that underlie changes in the production of
      eicosanoids after prolonged exposure of mast cells to Ag. Ag stimulation of
      cultured RBL-2H3 mast cells resulted in increased expression of cyclooxygenase
      (COX-2) protein and message. Other eicosanoid-related enzymes, namely COX-1, 5
      lipoxygenase, and cytosolic phospholipase A(2) were not induced. Activation of
      extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen
      activated protein (MAP) kinase preceded the induction of COX-2, whereas
      phosphatidylinositol 3' kinase and its substrate, Akt, were constitutively
      activated in RBL-2H3 cells. Studies with pharmacologic inhibitors indicated that
      of these kinases, only p38 MAP kinase regulated expression of COX-2. The
      induction of COX-2 was blocked by the p38 MAP kinase inhibitor SB202190, even
      when added 12-16 h after stimulation with Ag when p38 MAP kinase activity had
      returned to near basal, but still minimally elevated, levels. Interestingly,
      expression of COX-2 as well as cytosolic phospholipase A(2) and 5-lipoxygenase
      were markedly reduced by SB202190 in unstimulated cells. Collectively, the
      results imply that p38 MAP kinase regulates expression of eicosanoid-related
      enzymes, passively or actively, at very low levels of activity in RBL-2H3 cells.
      Also, comparison with published data suggest that different MAP kinases regulate
      induction of COX-2 in inflammatory cells of different and even similar phenotype
      and suggest caution in extrapolating results from one type of cell to another.

PMID- 11466387
TI  - RANTES-induced chemokine cascade in dendritic cells.
AB  - Dendritic cells (DC) are the most potent APCs and the principal activators of
      naive T cells. We now report that chemokines can serve as activating agents for
      immature DC. Murine bone marrow-derived DC respond to the CC chemokine RANTES (10
      100 ng/ml) by production of proinflammatory mediators. RANTES induces rapid
      expression of transcripts for the CXC chemokines KC and macrophage inflammatory
      protein (MIP)-2, the CC chemokines MIP-1beta and MIP-1alpha, and the cytokines
      TNF-alpha and IL-6. Synthesis of KC, IL-6, and TNF-alpha proteins were also
      demonstrated. After 4 h, autoinduction of RANTES transcripts was observed. These
      responses are chemokine specific. Although DC demonstrated weak responses to
      eotaxin, DC failed to respond to other chemokines including KC, MIP-2, stromal
      derived factor-1alpha, MIP-1beta, MIP-1alpha, monocyte chemoattractant protein-1,
      T cell activation gene 3, or thymus-derived chemotactic agent 4. In addition,
      RANTES treatment up-regulated expression of an orphan chemokine receptor termed
      Eo1. Chemokine induction was also observed after treatment of splenic DC and
      neonatal microglia with RANTES, but not after treatment of thymocytes or
      splenocytes depleted of adherent cells. TNF-alpha-treated DC lose responsiveness
      to RANTES. DC from mice deficient for CCR1, CCR3, and CCR5 respond to RANTES,
      indicating that none of these receptors are exclusively used to initiate the
      chemokine cascade. RANTES-mediated chemokine amplification in DC may prolong
      inflammatory responses and shape the microenvironment, potentially enhancing
      acquired and innate immune responses.

PMID- 11466388
TI  - Evidence of IL-18 as a novel angiogenic mediator.
AB  - Angiogenesis, or new blood vessel growth, is a key process in the development of
      synovial inflammation in rheumatoid arthritis (RA). Integral to this pathologic
      proliferation are proinflammatory cytokines. We hypothesized a role for IL-18 as
      an angiogenic mediator in RA. We examined the effect of human IL-18 on human
      microvascular endothelial cell (HMVEC) migration. IL-18 induced HMVEC migration
      at 1 nM (p < 0.05). RA synovial fluids potently induced endothelial cell
      migration, but IL-18 immunodepletion resulted in a 68 +/- 5% decrease in HMVEC
      migration (p < 0.05). IL-18 appears to act on HMVECs via alpha(v)beta(3)
      integrin. To test whether IL-18 induced endothelial cell tube formation in vitro,
      we quantitated the degree of tube formation on Matrigel matrix. IL-18, 1 or 10
      nM, resulted in a 77% or 87% increase in tube formation compared with control (p
      < 0.05). To determine whether IL-18 may be angiogenic in vivo, we implanted IL-18
      in Matrigel plugs in mice, and IL-18 at 1 and 10 nM induced angiogenesis (p <
      0.05). The angiogenesis observed appears to be independent of the contribution of
      local TNF-alpha, as evidenced by adding neutralizing anti-TNF-alpha Ab to the
      Matrigel plugs. In an alternative in vivo model, sponges embedded with IL-18 or
      control were implanted into mice. IL-18 (10 nM) induced a 4-fold increase in
      angiogenesis vs the control (p < 0.05). These findings support a novel function
      for IL-18 as an angiogenic factor in RA and may elucidate a potential therapeutic
      target for angiogenesis-directed diseases.

PMID- 11466389
TI  - CCAAT-enhancer-binding protein beta (C/EBP beta) activates CCR5 promoter:
      increased C/EBP beta and CCR5 in T lymphocytes from HIV-1-infected individuals.
AB  - C/EBPbeta is a member of a family of leucine zipper transcription factors that
      are involved in regulating the expression of several cytokines, including IL-1,
      IL-6, IL-8, TNF, and macrophage-inflammatory protein-1alpha. We identified
      multiple C/EBPbeta binding sites within the gene for CCR5, suggesting that
      C/EBPbeta may be involved in its regulation. Transient transfection experiments
      in both myeloid and lymphoid cells showed an increase in CCR5 promoter-driven
      green fluorescent protein production in the presence of C/EBPbeta. Deletion
      analysis identified two C/EBPbeta-responsive regions in the CCR5 gene, one in the
      promoter region and one at the 3' part of the intron. We provide evidence that,
      in myeloid cells (U937), C/EBPbeta independently activates CCR5 expression
      through sites located either in the promoter region or in the intron of the CCR5
      gene. In contrast, in lymphoid cells (Jurkat) the presence of the intronic cis
      regulatory regions is required for C/EBPbeta-mediated activation. In agreement
      with the functional data, EMSA demonstrated that in both myeloid and lymphoid
      cells C/EBPbeta binds specifically to sites present in the intron, whereas
      interaction with the sites located in the promoter was cell type specific and was
      detected only in myeloid cells. Analysis of C/EBPbeta in primary PBMCs obtained
      from HIV-1-infected individuals revealed a significant increase in C/EBPbeta
      expression. The enhanced C/EBPbeta activity correlated with a higher frequency of
      circulating CCR5(+) lymphocytes in AIDS patients and with a decline in CD4
      lymphocyte numbers. Taken together, these results suggest that C/EBPbeta is an
      important regulator of CCR5 expression and may play a relevant role in the
      pathogenesis of HIV disease.

PMID- 11466390
TI  - Inhibition of H2 histamine receptor-mediated cation channel opening by protein
      kinase C in human promyelocytic cells.
AB  - Histamine, through H(2) receptors, triggers a prominent rise in intracellular
      free Ca(2+) concentration ([Ca(2+)](i)) in addition to an elevation of cAMP level
      in HL-60 promyelocytes. Here we show that the histamine-induced [Ca(2+)](i) rise
      was due to influx of Ca(2+) from the extracellular space, probably through
      nonselective cation channels, as incubation of the cells with SKF 96365 abolished
      the histamine-induced [Ca(2+)](i) rise, Na(+) influx, and membrane
      depolarization. The Ca(2+) influx was specifically inhibited by pretreatment of
      the cells with PMA or extracellular ATP with 50% inhibitory concentrations of
      0.12 +/- 0.03 nM and 185 +/- 17 microM, respectively. Western blot analysis of
      protein kinase C (PKC) isoforms revealed that PMA (< or =1 nM) and ATP (300
      microM) caused selective translocation of PKC-delta to the particulate/membrane
      fraction. Costimulation of the cells with histamine and SKF 96365 partially
      reduced histamine-induced granulocytic differentiation, which was evaluated by
      looking at the extent of fMet-Leu-Phe-induced [Ca(2+)](i) rise and superoxide
      generation. In conclusion, nonselective cation channels are opened by stimulation
      of the H(2) receptor, and the channels are at least in part involved in the
      induction of histamine-mediated differentiation processes. Both effects of
      histamine were selectively inhibited probably by the delta isoform of PKC in HL
      60 cells.

PMID- 11466391
TI  - Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway
      proteins do not occur in a mouse ovalbumin-challenge model of pulmonary
      inflammation.
AB  - Paradigms of eosinophil effector function in the lungs of asthma patients
      invariably depend on activities mediated by cationic proteins released from
      secondary granules during a process collectively referred to as degranulation. In
      this study, we generated knockout mice deficient for eosinophil peroxidase (EPO)
      to assess the role(s) of this abundant secondary granule protein in an OVA
      challenge model. The loss of EPO had no effect on the development of OVA-induced
      pathologies in the mouse. The absence of phenotypic consequences in these
      knockout animals extended beyond pulmonary histopathologies and airway changes,
      as EPO-deficient animals also displayed OVA-induced airway hyperresponsiveness
      after provocation with methacholine. In addition, EPO-mediated oxidative damage
      of proteins (e.g., bromination of tyrosine residues) recovered in bronchoalveolar
      lavage from OVA-treated wild-type mice was <10% of the levels observed in
      bronchoalveolar lavage recovered from asthma patients. These data demonstrate
      that EPO activities are inconsequential to the development of allergic pulmonary
      pathologies in the mouse and suggest that degranulation of eosinophils recruited
      to the lung in this model does not occur at levels comparable to those observed
      in humans with asthma.

PMID- 11466392
TI  - IL-13 induces airways hyperreactivity independently of the IL-4R alpha chain in
      the allergic lung.
AB  - The potent spasmogenic properties of IL-13 have identified this molecule as a
      potential regulator of airways hyperreactivity (AHR) in asthma. Although IL-13 is
      thought to primarily signal through the IL-13Ralpha1-IL-4Ralpha complex, the
      cellular and molecular components employed by this cytokine to induce AHR in the
      allergic lung have not been identified. By transferring OVA-specific CD4(+) T
      cells that were wild type (IL-13(+/+) T cells) or deficient in IL-13 (IL-13(-/-)
      T cells) to nonsensitized mice that were then challenged with OVA aerosol, we
      show that T cell-derived IL-13 plays a key role in regulating AHR, mucus
      hypersecretion, eotaxin production, and eosinophilia in the allergic lung.
      Moreover, IL-13(+/+) T cells induce these features (except mucus production) of
      allergic disease independently of the IL-4Ralpha chain. By contrast, IL-13(+/+) T
      cells did not induce disease in STAT6-deficient mice. This shows that IL-13
      employs a novel component of the IL-13 receptor signaling system that involves
      STAT6, independently of the IL-4Ralpha chain, to modulate pathogenesis. We show
      that this novel pathway for IL-13 signaling is dependent on T cell activation in
      the lung and is critically linked to downstream effector pathways regulated by
      eotaxin and STAT6.

PMID- 11466393
TI  - Increased entry into the IFN-gamma effector pathway by CD4+ T cells selected by I
      Ag7 on a nonobese diabetic versus C57BL/6 genetic background.
AB  - IFN-gamma-mediated Th1 effects play a major role in the pathogenesis of
      autoimmune diabetes in nonobese diabetic (NOD) mice. We analyzed functional
      responses of CD4(+) T cells from NOD and B6.G7 MHC congenic mice, which share the
      H2(g7) MHC region but differ in their non-MHC genetic background. T cells from
      each strain proliferated equally to panstimulation with T cell lectins as well as
      to stimulation with glutamic acid decarboxylase 524-543 (self) and hen egg
      lysozyme 11-23 (foreign) I-A(g7)-binding peptide epitopes. Despite comparable
      proliferative responses, NOD CD4(+) T cells had significantly increased IFN-gamma
      intracellular/extracellular protein and mRNA responses compared with B6.G7 T
      cells as measured by intracellular cytokine analysis, time resolved fluorometry,
      and RNase protection assays. The increased IFN-gamma production was not due to an
      increase in the amount of IFN-gamma produced per cell but to an increase in the
      number of NOD CD4(+) T cells entering the IFN-gamma-producing pathway. The
      increased IFN-gamma response in NOD mice was not due to increased numbers of
      activated precursors as measured by activation/memory markers. B6.G7 lymphoid
      cells demonstrated an absolute decrease in IFN-gamma mRNA, an increase in IL-4
      mRNA production, and a significantly decreased IFN-gamma:IL-4 mRNA transcript
      ratio compared with NOD cells. CD4(+) T cells from C57BL6 mice also showed
      significantly decreased IFN-gamma production compared with CD4(+) T cells from
      NOD.H2(b) MHC-congenic mice (which have an H2(b) MHC region introgressed onto an
      NOD non-MHC background). Therefore, the NOD non-MHC background predisposes to a
      quantitatively increased IFN-gamma response, independent of MHC class II-mediated
      T cell repertoire selection, even when compared with a prototypical Th1 strain.

PMID- 11466394
TI  - Administration of pentoxifylline during allergen sensitization dissociates
      pulmonary allergic inflammation from airway hyperresponsiveness.
AB  - Asthma, a chronic inflammatory disease characterized by intermittent, reversible
      airflow obstruction and airway hyperresponsiveness (AHR), is classically
      characterized by an excess of Th2 cytokines (IL-13, IL-4) and depletion of Th1
      cytokines (IFN-gamma, IL-12). Recent studies indicating an important role for Th1
      immunity in the development of AHR with allergic inflammation suggest that
      Th1/Th2 balance may be important in determining the association of AHR with
      allergic inflammation. We hypothesized that administration of pentoxifylline
      (PTX), a phosphodiesterase inhibitor known to inhibit Th1 cytokine production,
      during allergen (OVA) sensitization and challenge would lead to attenuation of
      AHR in a murine model of allergic pulmonary inflammation. We found that PTX
      treatment led to attenuation of AHR when administered at the time of allergen
      sensitization without affecting other hallmarks of pulmonary allergic
      inflammation. Attenuation of AHR with PTX treatment was found in the presence of
      elevated bronchoalveolar lavage fluid levels of the Th2 cytokine IL-13 and
      decreased levels of the Th1 cytokine IFN-gamma. PTX treatment during allergen
      sensitization leads to a divergence of AHR and pulmonary inflammation following
      allergen challenge.

PMID- 11466395
TI  - The generation of both T killer and Th cell clones specific for the tumor
      associated antigen HER2 using retrovirally transduced dendritic cells.
AB  - Induction of antitumor immunity involves the presence of both CD8(+) CTLs and
      CD4(+) Th cells specific for tumor-associated Ags. Attempts to eradicate cancer
      by adoptive T cell transfer have been limited due to the difficulty of generating
      T cells with defined Ag specificity. The current study focuses on the generation
      of CTL and Th cells against the tumor-associated Ag HER2 using autologous
      dendritic cells (DC) derived from CD34(+) hematopoietic progenitor cells which
      have been retrovirally transduced with the human epidermal growth factor receptor
      2 (HER2) gene. HER2-transduced DC elicited HER2-specific CD8(+) CTL that lyse
      HER2-overexpressing tumor cells in context of distinct HLA class I alleles. The
      induction of both HLA-A2 and -A3-restricted HER2-specific CTL was verified on a
      clonal level. In addition, retrovirally transduced DC induced CD4(+) Th1 cells
      recognizing HER2 in context with HLA class II. HLA-DR-restricted CD4(+) T cells
      were cloned that released IFN-gamma upon stimulation with DC pulsed with the
      recombinant protein of the extracellular domain of HER2. These data indicate that
      retrovirally transduced DC expressing the HER2 molecule present multiple peptide
      epitopes and subsequently elicit HER2-specific CTL and Th1 cells. The method of
      stimulating HER2-specific CD8(+) and CD4(+) T cells with retrovirally transduced
      DC was successfully implemented for generating HER2-specific CTL and Th1 clones
      from a patient with HER2-overexpressing breast cancer. The ability to generate
      and expand HER2-specific, HLA-restricted CTL and Th1 clones in vitro facilitates
      the development of immunotherapy regimens, in particular the adoptive transfer of
      both autologous HER2-specific T cell clones in patients with HER2-overexpressing
      tumors without the requirement of defining immunogenic peptides.

PMID- 11466396
TI  - Induction of experimental autoimmune thyroiditis in IL-12-/- mice.
AB  - Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by transfer
      of mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg
      and anti-IL-2R or MTg and IL-12. Previous work suggested that IL-12 was required
      in vitro for development of G-EAT. To determine whether IL-12 was also required
      during the induction and/or effector phases, DBA/1 mice with a disrupted IL-12
      P40 gene (IL-12(-/-)) were used for EAT induction. Cells from MTg-sensitized
      IL12(-/-) donors activated in vitro by MTg or MTg and anti-IL2R induced severe
      EAT in recipient mice. Compared with effector cells from IL-12(+/+) donors,
      effector cells from IL-12(-/-) donors induced thyroid lesions dominated by
      lymphocytes with minimal granulomatous changes. Thyroids of recipients of IL-12(
      /-) cells expressed less IFN-gamma mRNA and more TGF-beta, IL-4, and IL-10
      compared with recipients of IL-12(+/+) cells. When IL-12 was added during in
      vitro activation, cells from both IL-12(-/-) and IL-12(+/+) donors induced severe
      G-EAT, and expression of all cytokines except IL-12 was comparable in thyroids of
      both IL-12(+/+) and IL-12(-/-) recipients. Transfer of cells from IL-12(+/+) or
      IL-12(-/-) donors into IL-12(+/+) or IL-12(-/-) recipients indicated that IL-12
      expressed in thyroids was derived from recipients. Thus, endogenous IL-12 is not
      absolutely essential for the sensitization and activation of EAT effector cells
      to induce severe EAT, although it is required in vitro to promote activation of
      cells to induce severe granulomatous histopathology.

PMID- 11466397
TI  - Autoantigen glycoprotein 70 expression is regulated by a single locus, which acts
      as a checkpoint for pathogenic anti-glycoprotein 70 autoantibody production and
      hence for the corresponding development of severe nephritis, in lupus-prone PXSB
      mice.
AB  - Retroviral envelope glycoprotein gp70 is present in the sera of immunologically
      normal and autoimmune-prone strains of mice. However, only lupus-prone mice
      spontaneously develop gp70-anti-gp70 immune complexes (gp70IC), and these have
      been implicated in the development of nephritis. We investigated the genetic
      factors that affect the production of both free serum gp70 and gp70IC in the
      lupus-prone BXSB mouse strain by analyzing (BXSB x (C57BL/10 x BXSB)F(1))- and
      (C57BL/10 x (C57BL/10 x BXSB)F(1))-backcrossed male mice. Production of gp70
      mapped to a single major locus located on chromosome 13 (Bxs6) with a maximum log
      likelihood of the odds of 36.7 (p = 1.6 x 10(-38)). The level of gp70IC was
      highly dependent on Bxs6-related gp70 production, and high titer autoantibody
      production only occurred when serum gp70 levels were greater than a threshold
      value of approximately 4.0 microg/ml. The subdivision of the (BXSB x (C57BL/10 x
      BXSB)F(1))-backcrossed mice into those homozygous or heterozygous for Bxs6
      enabled a remarkable association to be observed between high levels of gp70IC and
      severe nephritis in the Bxs6 homozygote population. A further mapping study in
      these two subgroups identified a previously unrecognized interval associated with
      the production of autoantibodies.

PMID- 11466398
TI  - Allergen-derived T cell peptide-induced late asthmatic reactions precede the
      induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic
      subjects.
AB  - Allergen-derived peptides can induce T cell tolerance in naive and Ag-primed
      mice. This is preceded by transient T cell activation. In humans, intradermal
      administration of short allergen-derived T cell peptide epitopes provokes IgE
      independent isolated late asthmatic reactions (LARs) in sensitized subjects. In
      this study, we determine whether, as in mouse models, such peptides produce
      hyporesponsiveness to rechallenge with peptides, or whole allergen, either
      clinically or in terms of in vitro T cell responses. We found that a second
      injection of cat allergen (Fel d 1)-derived T cell peptides was associated with a
      marked reduction, or absence, of the LAR, and that up to 40 wk was required for
      return to baseline values. The cutaneous late-phase reaction to whole cat dander
      was also inhibited, even in subjects who did not experience an initial LAR. These
      observations were associated with a significant decrease in peptide- and whole
      allergen-induced proliferation of PBMCs and the production of IL-4, IL-13, and
      IFN-gamma in cultures. Thus, allergen-derived peptides induce tolerance to
      subsequent peptide injection in the target organ (the lung), reduce late-phase
      cutaneous responsiveness to whole allergen, and alter in vitro T cell reactivity.

PMID- 11466399
TI  - Apoptosis and altered dendritic cell homeostasis in lupus nephritis are limited
      by anti-CD154 treatment.
AB  - Autoimmunity results from a failure in central and/or peripheral tolerance;
      however, the events that initiate and maintain this dysfunction remain unclear.
      To better understand the mediators involved in autoimmunity, we investigated the
      cellular mechanisms maintaining disease in the (SWR x NZB)F(1) (SNF(1)) mouse
      model of systemic lupus erythematosus. Previously, we have shown that
      autoimmunity in this model is dependent on CD40-CD154 interactions. Herein, our
      studies reveal that the severity of disease in SNF(1) mice correlates with a
      marked increase in the frequency of apoptotic splenocytes, including a higher
      proportion of apoptotic dendritic cells (DC) in vivo. In addition, we demonstrate
      a significant disease-related increase in the absolute number of splenic
      CD11c(high) DC. The increased DC number appears to be attributable to DC
      proliferation and enhanced migration to the spleen, most likely induced by
      elevated splenic expression of secondary lymphoid chemokine. Importantly, these
      imbalances in apoptosis, secondary lymphoid chemokine expression, and DC
      homeostasis were reduced or normalized by anti-CD154 treatment. Thus, our data
      demonstrate CD154-dependent regulation of apoptosis and DC homeostasis in mice
      with lupus-like autoimmune disease. We suggest that these mechanisms comprise an
      autostimulatory loop, maintaining the cascade of autoimmunity by DC presentation
      of self-Ags derived from apoptotic cells and CD154-mediated costimulation.

PMID- 11466400
TI  - MHC class I-restricted determinants on the glutamic acid decarboxylase 65
      molecule induce spontaneous CTL activity.
AB  - CD4(+) T cell responses to glutamic acid decarboxylase (GAD65) spontaneously
      arise in nonobese diabetic (NOD) mice before the onset of insulin-dependent
      diabetes mellitus (IDDM) and may be critical to the pathogenic process. However,
      since both CD4(+) and CD8(+) T cells are involved in autoimmune diabetes, we
      sought to determine whether GAD65-specific CD8(+) T cells were also present in
      prediabetic NOD mice and contribute to IDDM. To refine the analysis, putative
      K(d)-binding determinants that were proximal to previously described dominant Th
      determinants (206-220 and 524-543) were examined for their ability to elicit
      cytolytic activity in young NOD mice. Naive NOD spleen cells stimulated with
      GAD65 peptides 206-214 (p206) and 546-554 (p546) produced IFN-gamma and showed Ag
      specific CTL responses against targets pulsed with homologous peptide.
      Conversely, several GAD peptides distal to the Th determinants, and control K(d)
      binding peptides did not induce similar responses. Spontaneous CTL responses to
      p206 and p546 were mediated by CD8(+) T cells that are capable of lysing GAD65
      expressing target cells, and p546-specific T cells transferred insulitis to
      NOD.scid mice. Young NOD mice pretreated with p206 and p546 showed reduced CTL
      responses to homologous peptides and a delay in the onset of IDDM. Thus, MHC
      class I-restricted responses to GAD65 may provide an inflammatory focus for the
      generation of islet-specific pathogenesis and beta cell destruction. This report
      reveals a potential therapeutic role for MHC class I-restricted peptides in
      treating autoimmune disease and revisits the notion that the CD4- and CD8
      inducing determinants on some molecules may benefit from a proximal relationship.

PMID- 11466401
TI  - Dendritic cells (DCs) in rheumatoid arthritis (RA): progenitor cells and soluble
      factors contained in RA synovial fluid yield a subset of myeloid DCs that
      preferentially activate Th1 inflammatory-type responses.
AB  - There is evidence that mature dendritic cells (DCs) present in the rheumatoid
      arthritis (RA) joint mediate immunopathology in RA. In this study, we indicate
      that early myeloid progenitors for DCs and DC growth factors existing in RA
      synovial fluid (SF) are also likely participants in the RA disease process. A
      fraction of cells lacking markers associated with mature DCs or DC precursors and
      enriched in CD34(negative) myeloid progenitors was isolated from RA SF. These
      cells proliferated extensively when cultured in vitro with cytokines that promote
      the growth of myeloid DCs (GM-CSF/TNF/stem cell factor/IL-4) and, to a lesser
      degree, when cultured with monocyte/granulocyte-restricted growth factors (M
      CSF/GM-CSF). Mature DCs derived from RA SF progenitors with CD14-DC cytokines
      known to be prevalent in the inflamed RA joint (GM-CSF/TNF/stem cell factor/IL
      13) were potent stimulators of allogeneic T cells and inflammatory-type Th1
      responses and included CD14-DC subtypes. Cell-free RA SF facilitated DC
      maturation from myeloid progenitors, providing direct evidence that the inflamed
      RA joint environment instructs DC growth. Enhanced development of CD14-derived
      DCs was correlated with the presence of soluble TNFR (p55), raising the
      possibility that soluble TNFR also regulate CD14-derived DC growth in vivo. SF
      from patients with osteoarthritis contained neither myeloid DC progenitors nor DC
      growth factors. The existence of DC progenitors and myeloid DC growth factors in
      RA SF supports the concept that RA SF may be a reservoir for joint-associated DCs
      and reveals a compelling mechanism for the amplification and perpetuation of DC
      driven responses in the RA joint, including inflammatory-type Th1 responses.

PMID- 11466402
TI  - Il-13 and IFN-gamma: interactions in lung inflammation.
AB  - Chronic inflammatory diseases of the lungs, such as asthma, are frequently
      associated with mixed (Th2 and Th1) T cell responses. We examined the impact of
      critical Th1 and Th2 cytokines, IFN-gamma and IL-13, on the responses in the
      lungs. In a mouse model of airway inflammation induced by mixed T cell responses,
      the number of Th1 (IFN-gamma-positive) cells was found to be negatively
      correlated with airway hyperreactivity. In these mice, blockade of IL-13
      partially inhibited airway hyperreactivity and goblet cell hyperplasia but not
      inflammation. In contrast, in mice that responded with a polarized Th2 response
      to the same Ag, blockade of IL-13 inhibited airway hyperreactivity, goblet cell
      hyperplasia, and airway inflammation. These results indicated that the presence
      of IFN-gamma would modulate the effects of IL-13 in the lungs. To test this
      hypothesis, wild-type mice were given recombinant cytokines intranasally. IFN
      gamma inhibited IL-13-induced goblet cell hyperplasia and airway eosinophilia. At
      the same time, IFN-gamma and IL-13 potentiated each other's effects. In the
      airways of mice given IL-13 and IFN-gamma, levels of IL-6 were increased as well
      as numbers of NK cells and of CD11c-positive cells expressing MHC class II and
      high levels of CD86. In conclusion, IFN-gamma has double-sided effects
      (inhibiting some, potentiating others) on IL-13-induced changes in the lungs.
      This may be the reason for the ambiguous role of Th1 responses on Th2 response
      induced lung injury.

PMID- 11466403
TI  - Adenoviral augmentation of elafin protects the lung against acute injury mediated
      by activated neutrophils and bacterial infection.
AB  - During acute pulmonary infection, tissue injury may be secondary to the effects
      of bacterial products or to the effects of the host inflammatory response. An
      attractive strategy for tissue protection in this setting would combine
      antimicrobial activity with inhibition of human neutrophil elastase (HNE), a key
      effector of neutrophil-mediated tissue injury. We postulated that genetic
      augmentation of elafin (an endogenous inhibitor of HNE with intrinsic
      antimicrobial activity) could protect the lung against acute inflammatory injury
      without detriment to host defense. A replication-deficient adenovirus encoding
      elafin cDNA significantly protected A549 cells against the injurious effects of
      both HNE and whole activated human neutrophils in vitro. Intratracheal
      replication-deficient adenovirus encoding elafin cDNA significantly protected
      murine lungs against injury mediated by Pseudomonas aeruginosa in vivo. Genetic
      augmentation of elafin therefore has the capacity to protect the lung against the
      injurious effects of both bacterial pathogens resistant to conventional
      antibiotics and activated neutrophils.

PMID- 11466404
TI  - Mutation in the class II trans-activator leading to a mild immunodeficiency.
AB  - The expression of MHC class II molecules is essential for all Ag-dependent immune
      functions and is regulated at the transcriptional level. Four trans-acting
      proteins control the coordinate expression of MHC class II molecules: class II
      trans-activator (CIITA), regulatory factor binding to the X box (RFX)-associated
      protein; RFX protein containing ankyrin repeats, and RFX5. In humans, defects in
      these genes result in MHC class II expression deficiency and cause combined
      immunodeficiency. Most patients with this deficiency suffer from severe recurrent
      infections that frequently lead to death during early childhood. We investigated
      three sisters, now ages 21, 22, and 24 years, in whom MHC-II deficiency was
      detected. Even though the eldest sibling was asymptomatic and the other two had
      only mild immunodeficiency, none of the three class II isotypes was expressed on
      T cell blasts, fibroblasts, EBV B cell lines, or epidermal dendritic cells.
      Residual HLA-II expression was detected in fresh PBMC. Somatic complementation
      identified the disease as CIITA deficiency. A homozygous T1524C (L469P)
      substitution was found in the coding region of the CIITA cDNA and was shown to be
      responsible for the defect in MHC-II expression. This missense mutation prevents
      the normal functioning of MHC-II but does not lead to the nuclear exclusion of
      the L469P CIITA. Transfection experiments demonstrated that the CIITA L469P
      mutant had residual MHC class II trans activation activity, which might explain
      the unusual clinical course of the patients studied. This study shows that an
      attenuated clinical phenotype or an asymptomatic clinical course can be observed
      in patients despite a profound defect in the expression of MHC class II genes.
      The frequency of the inherited MHC class II deficiency might thus be
      underestimated.

PMID- 11466405
TI  - Cross-presentation by dendritic cells of tumor antigen expressed in apoptotic
      recombinant canarypox virus-infected dendritic cells.
AB  - We have investigated the possible usefulness of recombinant canarypox virus
      (ALVAC) encoding the melanoma-associated Ag, Melan-A/MART-1 (MART-1), in cancer
      immunotherapy, using a dendritic cell (DC)-based approach. ALVAC MART-1-infected
      DC express, and are able to process and present, the Ag coded by the viral
      vector. One consistent feature of infection by ALVAC is that these viruses induce
      apoptosis, and we show cross-presentation of Ag when uninfected DC are cocultured
      with ALVAC MART-1-infected DC. Uptake of apoptotic virally infected DC by
      uninfected DC and subsequent expression of tumor Ag in the latter were verified
      by flow cytometry analysis, image cytometry, and confocal microscopy. Functional
      activity was monitored in vitro by the stimulation of a MART-1-specific cytotoxic
      T cell clone. Heightened efficiency in Ag presentation is evidenced in the 2- to
      3-fold increase in IFN-gamma production by the T cell clone, as compared with the
      ALVAC-infected DC alone. Cocultures of ALVAC MART-1-infected and uninfected DC
      are able to induce MART-1-specific T cell immune responses, as assessed by HLA
      class I/peptide tetramer binding, IFN-gamma ELISPOT assays, and cytotoxicity
      tests. Overall, our data indicate that DC infected with recombinant canarypox
      viruses may represent an efficient presentation platform for tumor Ags, which can
      be exploited in clinical studies.

PMID- 11466406
TI  - A Chlamydia pneumoniae-specific peptide induces experimental autoimmune
      encephalomyelitis in rats.
AB  - It has been reported recently that the bacterial respiratory pathogen Chlamydia
      pneumoniae is present in the cerebrospinal fluid of a subset of multiple
      sclerosis (MS) patients. However, it is not known whether this organism is a
      causative agent of MS, or merely an opportunistic pathogen that takes advantage
      of a disease process initiated by some other means. We report identification of a
      20-mer peptide from a protein specific to C. pneumoniae which shares a 7-aa motif
      with a critical epitope of myelin basic protein, a major CNS Ag targeted by the
      autoimmune response in MS. This bacterial peptide induces a Th1 response
      accompanied by severe clinical and histological experimental autoimmune
      encephalomyelitis in Lewis rats, a condition closely reflective of many aspects
      of MS. Studies with peptide analogues suggest that different populations of
      encephalitogenic T cells are activated by the C. pneumoniae and myelin basic
      protein Ags. Mild experimental autoimmune encephalomyelitis was also observed
      when rats were immunized with sonicated C. pneumoniae in CFA.

PMID- 11466407
TI  - Short-term kinetics of tumor antigen expression in response to vaccination.
AB  - The melanoma patient's immune response to tumor has been extensively studied.
      Yet, the frequently observed coexistence of tumor-associated Ag (TAA)-specific T
      cells with their target cells in vivo remains unexplained. Loss of TAA expression
      might contribute to this paradox. We studied TAA expression in metastases by
      obtaining fine-needle aspirations from 52 tumor lesions in 30 patients with
      melanoma before and soon after immunotherapy. Limitations due to low amounts of
      starting material were overcome with a high fidelity antisense RNA amplification
      method. TAA expression was measured by quantitative real-time PCR of anti-sense
      RNA. Decrease in gp100/Pmel-17 TAA preceded tumor disappearance in several
      instances and could be best explained by immune selection because most patients
      had received gp100/Pmel-17-specific vaccination. Conversely, immune selection was
      absent in nonregressing lesions. These observations suggest that vaccination,
      when successful, triggers a broad inflammatory reaction that can lead to tumor
      destruction despite immune selection. Additionally, lack of clinical response
      might be attributed to lack of this initiating event rather than immune escape.
      This study provides an insight into the natural history of tumors and defines a
      strategy for the characterization of gene expression in tumors during therapy.

PMID- 11466408
TI  - Intrathecal delivery of IFN-gamma protects C57BL/6 mice from chronic-progressive
      experimental autoimmune encephalomyelitis by increasing apoptosis of central
      nervous system-infiltrating lymphocytes.
AB  - The exclusive detrimental role of proinflammatory cytokines in demyelinating
      diseases of the CNS, such as multiple sclerosis, is controversial. Here we show
      that the intrathecal delivery of an HSV-1-derived vector engineered with the
      mouse IFN-gamma gene leads to persistent (up to 4 wk) CNS production of IFN-gamma
      and inhibits the course of a chronic-progressive form of experimental autoimmune
      encephalomyelitis (EAE) induced in C57BL/6 mice by myelin oligodendrocyte
      glycoprotein (MOG)(35-55). Mice treated with the IFN-gamma-containing vector
      before EAE onset showed an earlier onset but a milder course of the disease
      compared with control mice treated with the empty vector. In addition, 83% of IFN
      gamma-treated mice completely recovered within 25 days post immunization, whereas
      control mice did not recover up to 60 days post immunization. Mice treated with
      the IFN-gamma-containing vector within 1 wk after EAE onset partially recovered
      from the disease within 25 days after vector injection, whereas control mice
      worsened. Recovery from EAE in mice treated with IFN-gamma was associated with a
      significant increase of CNS-infiltrating lymphocytes undergoing apoptosis. During
      the recovery phase, the mRNA level of TNFR1 was also significantly increased in
      CNS-infiltrating cells from IFN-gamma-treated mice compared with controls. Our
      results further challenge the exclusive detrimental role of IFN-gamma in the CNS
      during EAE/multiple sclerosis, and indicate that CNS-confined inflammation may
      induce protective immunological countermechanisms leading to a faster clearance
      of encephalitogenic T cells by apoptosis, thus restoring the immune privilege of
      the CNS.

PMID- 11466409
TI  - B7 interactions with CD28 and CTLA-4 control tolerance or induction of mucosal
      inflammation in chronic experimental colitis.
AB  - CD28-B7 interaction plays a critical costimulatory role in inducing T cell
      activation, while CTLA-4-B7 interaction provides a negative signal that is
      essential in immune homeostasis. Transfer of CD45RB(high)CD4(+) T cells from
      syngeneic mice induces transmural colon inflammation in SCID recipients. This
      adoptive transfer model was used to investigate the contribution of B7-CD28/CTLA
      4 interactions to the control of intestinal inflammation. CD45RB(high)CD4(+)
      cells from CD28(-/-) mice failed to induce mucosal inflammation in SCID
      recipients. Administration of anti-B7.1 (but not anti-B7.2) after transfer of
      wild-type CD45RB(high)CD4(+) cells also prevented wasting disease with colitis,
      abrogated leukocyte infiltration, and reduced production of proinflammatory
      cytokines IL-2 and IFN-gamma by lamina propria CD4(+) cells. In contrast, anti
      CTLA-4 treatment led to deterioration of disease, to more severe inflammation,
      and to enhanced production of proinflammatory cytokines. Of note, CD25(+)CD4(+)
      cells from CD28(-/-) mice similar to those from the wild-type mice were efficient
      to prevent intestinal mucosal inflammation induced by the wild-type CD45RB(high)
      cells. The inhibitory functions of these regulatory T cells were effectively
      blocked by anti-CTLA-4. These data show that the B7-CD28 costimulatory pathway is
      required for induction of effector T cells and for intestinal mucosal
      inflammation, while the regulatory T cells function in a CD28-independent way.
      CTLA-4 signaling plays a key role in maintaining mucosal lymphocyte tolerance,
      most likely by activating the regulatory T cells.

PMID- 11466410
TI  - Inflammatory genes are upregulated in expanded ataxin-3-expressing cell lines and
      spinocerebellar ataxia type 3 brains.
AB  - Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine disorder caused by a CAG
      repeat expansion in the coding region of a gene encoding ataxin-3. To study
      putative alterations of gene expression induced by expanded ataxin-3, we
      performed PCR-based cDNA subtractive hybridization in a cell culture model of
      SCA3. In rat mesencephalic CSM14.1 cells stably expressing expanded ataxin-3, we
      found a significant upregulation of mRNAs encoding the endopeptidase matrix
      metalloproteinase 2 (MMP-2), the transmembrane protein amyloid precursor protein,
      the interleukin-1 receptor-related Fos-inducible transcript, and the cytokine
      stromal cell-derived factor 1alpha (SDF1alpha). Immunohistochemical studies of
      the corresponding or associated proteins in human SCA3 brain tissue confirmed
      these findings, showing increased expression of MMP-2 and amyloid beta-protein
      (Abeta) in pontine neurons containing nuclear inclusions. In addition,
      extracellular Abeta-immunoreactive deposits were detected in human SCA3 pons.
      Furthermore, pontine neurons of SCA3 brains strongly expressed the
      antiinflammatory interleukin-1 receptor antagonist, the proinflammatory cytokine
      interleukin-1beta, and the proinflammatory chemokine SDF1. Finally, increased
      numbers of reactive astrocytes and activated microglial cells were found in SCA3
      pons. These results suggest that inflammatory processes are involved in the
      pathogenesis of SCA3.

PMID- 11466411
TI  - Gap junctions mediate electrical signaling and ensuing cytosolic Ca2+ increases
      between chromaffin cells in adrenal slices: A role in catecholamine release.
AB  - In adrenal chromaffin cells, a rise in cytosolic calcium concentration
      ([Ca(2+)]i) is a key event in the triggering of catecholamine exocytosis after
      splanchnic nerve activation. Action potential- or nicotine-induced [Ca(2+)]i
      transients are well described in individual chromaffin cells, but whether they
      remain spatially confined to the stimulated cell or propagate to adjacent cells
      is not yet known. To address this issue, the spatiotemporal organization of
      electrical and associated Ca(2+) events between chromaffin cells was investigated
      using the patch-clamp technique and real-time confocal imaging in rat acute
      adrenal slices. Spontaneous or electrically evoked action potential-driven
      [Ca(2+)]i transients were simultaneously detected in neighboring cells. This was
      likely attributable to gap junction-mediated electrotonic communication, as shown
      by (1) the bidirectional reflection of voltage changes monitored between cell
      pairs, (2) Lucifer yellow (LY) diffusion between cells exhibiting spontaneous
      synchronized [Ca(2+)]i transients, and (3) the reduction of LY diffusion using
      the uncoupling agent carbenoxolone. Furthermore, transcripts encoding two
      connexins (Cx36 and Cx43) were found in single chromaffin cells. This gap
      junctional coupling was activated after a synaptic-like application of nicotine
      that mediated synchronous multicellular [Ca(2+)]i increases. In addition,
      nicotinic stimulation of a single cell triggered catecholamine release in coupled
      cells, as shown by amperometric detection of secretory events. Functional
      coupling between chromaffin cells in situ may represent an efficient complement
      to synaptic transmission to amplify catecholamine release after synaptic
      stimulation of a single excited chromaffin cell.

PMID- 11466412
TI  - Nerve growth factor activates persistent Rap1 signaling in endosomes.
AB  - We investigated a role for endogenous Rap1, a small monomeric GTP-binding protein
      of the Ras family, in nerve growth factor (NGF) signaling in PC12 cells. Although
      both epidermal growth factor (EGF) and NGF caused transient activation of Ras,
      only NGF induced the activation of Rap1. Moreover, Rap1 activation was sustained
      for hours, an effect that matched the sustained activation of the mitogen
      activated protein kinase (MAPK) pathway. To investigate the molecular basis for
      Rap1 activation, we examined complexes containing C3G, a guanine nucleotide
      exchange factor for Rap1, and CrkL, an adapter protein known to influence Rap1
      signaling. NGF induced the formation of a long-lived complex containing
      C3G/CrkL/Shp2/Gab2/TrkA. Linking the complex to Rap1 activation, we
      coprecipitated activated TrkA and activated MAPK with activated Rap1 in NGF
      treated cells. Confocal microscopy and subcellular fractionation showed that
      activated Rap1 and the other proteins of the signaling complex were present in
      endosomes. Pretreatment of PC12 cells with brefeldin A (BFA), which disrupts the
      Golgi and endosomal compartments, had little effect on Ras activation but
      strongly inhibited NGF-induced Rap1 activation and continuing MAPK activation. We
      propose that endosomes are a site from which NGF induces the prolonged activation
      of Rap1 and MAPK.

PMID- 11466413
TI  - PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines
      of hippocampal neurons and reduces surface levels of the AMPA-type glutamate
      receptor subunit 2.
AB  - The PICK1 protein interacts in neurons with the AMPA-type glutamate receptor
      subunit 2 (GluR2) and with several other membrane receptors via its single PDZ
      domain. We show that PICK1 also binds in neurons and in heterologous cells to
      protein kinase Calpha (PKCalpha) and that the interaction is highly dependent on
      the activation of the kinase. The formation of PICK1-PKCalpha complexes is
      strongly induced by TPA, and PICK1-PKCalpha complexes are cotargeted with PICK1
      GluR2 complexes to spines, where GluR2 is found to be phosphorylated by PKC on
      serine 880. PICK1 also reduces the plasma membrane levels of the GluR2 subunit,
      consistent with a targeting function of PICK1 and a PKC-facilitated release of
      GluR2 from the synaptic anchoring proteins ABP and GRIP. This work indicates that
      PICK1 functions as a targeting and transport protein that directs the activated
      form of PKCalpha to GluR2 in spines, leading to the activity-dependent release of
      GluR2 from synaptic anchor proteins and the PICK1-dependent transport of GluR2
      from the synaptic membrane.

PMID- 11466414
TI  - Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and
      in vivo myelination.
AB  - To understand the cellular and in vivo functions of specific K(+) channels in
      glia, we have studied mice with a null mutation in the weakly inwardly rectifying
      K(+) channel subunit Kir4.1. Kir4.1-/- mice display marked motor impairment, and
      the cellular basis is hypomyelination in the spinal cord, accompanied by severe
      spongiform vacuolation, axonal swellings, and degeneration. Immunostaining in the
      spinal cord of wild-type mice up to postnatal day 18 reveals that Kir4.1 is
      expressed in myelin-synthesizing oligodendrocytes, but probably not in neurons or
      glial fibrillary acidic protein-positive (GFAP-positive) astrocytes. Cultured
      oligodendrocytes from developing spinal cord of Kir4.1-/- mice lack most of the
      wild-type K(+) conductance, have depolarized membrane potentials, and display
      immature morphology. By contrast, cultured neurons from spinal cord of Kir4.1-/-
      mice have normal physiological characteristics. We conclude that Kir4.1 forms the
      major K(+) conductance of oligodendrocytes and is therefore crucial for
      myelination. The Kir4.1 knock-out mouse is one of the few CNS dysmyelinating or
      demyelinating phenotypes that does not involve a gene directly involved in the
      structure, synthesis, degradation, or immune response to myelin. Therefore, this
      mouse shows how an ion channel mutation could contribute to the polygenic
      demyelinating diseases.

PMID- 11466415
TI  - Paralytic zebrafish lacking acetylcholine receptors fail to localize rapsyn
      clusters to the synapse.
AB  - Physiological analysis of two lines of paralytic mutant zebrafish, relaxed and
      sofa potato, reveals defects in distinct types of receptors in skeletal muscle.
      In sofa potato the paralysis results from failed synaptic transmission because of
      the absence of acetylcholine receptors, whereas relaxed mutants lack
      dihydropyridine receptor-mediated release of internal calcium in response to the
      muscle action potential. Synaptic structure and function appear normal in
      relaxed, showing that muscle paralysis per se does not impede proper synapse
      development. However, sofa potato mutants show incomplete development of the
      postsynaptic complex. Specifically, in the absence of ACh receptors, clusters of
      the receptor-aggregating protein rapsyn form in the extrasynaptic membrane but
      generally fail to localize to the subsynaptic region. Our results indicate that,
      although rapsyn molecules are capable of self-aggregation, interaction with ACh
      receptors is required for proper subsynaptic localization.

PMID- 11466416
TI  - Constitutive "light" adaptation in rods from G90D rhodopsin: a mechanism for
      human congenital nightblindness without rod cell loss.
AB  - A dominant form of human congenital nightblindness is caused by a gly90-->asp
      (G90D) mutation in rhodopsin. G90D has been shown to activate the
      phototransduction cascade in the absence of light in vitro. Such constitutive
      activity of G90D rhodopsin in vivo would desensitize rod photoreceptors and lead
      to nightblindness. In contrast, other rhodopsin mutations typically give rise to
      nightblindness by causing rod cell death. Thus, the proposed desensitization
      without rod degeneration would be a novel mechanism for this disorder. To explore
      this possibility, we induced mice to express G90D opsin in their rods and then
      examined rod function and morphology, after first crossing the transgenic animals
      with rhodopsin knock-out mice to obtain appropriate levels of opsin expression.
      The G90D mouse opsin bound the chromophore and formed a bleachable visual pigment
      with lambda(max) of 492 nm that supported rod photoresponses. (G+/-, R+/-)
      retinas, heterozygous for both G90D and wild-type (WT) rhodopsin, possessed
      normal numbers of photoreceptors and had a normal rhodopsin complement but
      exhibited considerable loss of rod sensitivity as measured
      electroretinographically. The rod photoresponses were desensitized, and the
      response time to peak was faster than in (R+/-) animals. An equivalent
      desensitization resulted by exposing WT retinas to a background light producing
      82 photoisomerizations rod(-1) sec(-1), suggesting that G90D rods in darkness act
      as if they are partially "light-adapted." Adding a second G90D allele gave (G+/+,
      R+/-) animals that exhibited a further increase of equivalent background light
      level but had no rod cell loss by 24 weeks of age. (G+/+, R-/-) retinas that
      express only the mutant rhodopsin develop normal rod outer segments and show
      minimal rod cell loss even at 1 year of age. We conclude that G90D is
      constitutively active in mouse rods in vivo but that it does not cause
      significant rod degeneration. Instead, G90D desensitizes rods by a process
      equivalent to light adaptation.

PMID- 11466417
TI  - Developmental regulation and specific brain distribution of phosphorabphilin.
AB  - Protein kinases and phosphatases play an important role in modulating synaptic
      transmission. The synaptic protein rabphilin associates with synaptic vesicles
      through the small GTPase Rab3A, binds Ca(2+) and phospholipids, and interacts
      with cytoskeletal elements, yet its function remains controversial. In this
      study, we have generated phosphospecific antibodies and studied the
      developmental, subcellular, and brain distribution of rabphilin phosphorylated at
      serine-234 and serine-274. Our results show that phosphorabphilin is present in
      vivo under basal conditions in a specific subset of synapses. The phosphorylated
      rabphilin is abundant in the cerebellum, midbrain, and medulla; phosphorabphilin
      is specifically enriched in the climbing fiber synapses of the cerebellar cortex.
      Its developmental profile reveals a sharp and transient increase at approximately
      postnatal day 16, a period critical for the activity-dependent pruning of
      supernumerary climbing fibers in the cerebellum. We propose that the
      phosphorylation of rabphilin regulates neuronal activity through development and
      in a synapse-specific manner.

PMID- 11466418
TI  - Physiological modulation of rabphilin phosphorylation.
AB  - The dynamic modulation of protein function by phosphorylation plays an important
      role in regulating synaptic plasticity. Several proteins involved in synaptic
      transmission have been shown to be targets of protein kinases and phosphatases. A
      thorough analysis of the physiological role of these modifications has been
      hampered by the lack of reagents that specifically recognize the phosphorylated
      states of these proteins. In this study we analyze the physiological modulation
      of rabphilin using phosphospecific antibodies. We show that phosphorylation on
      serine-234 and serine-274 of rabphilin is dynamically regulated both under basal
      and stimulated conditions by the activity of kinases and phosphatases. The two
      sites are differentially phosphorylated by the stimulation of various kinases,
      suggesting a possible convergence of different pathways to modulate the function
      of the protein. Maximal stimulation was observed under plasma membrane
      depolarizing conditions that trigger synaptic vesicle exocytosis. The increase in
      phosphorylation was critically dependent on external Ca(2+) and on the presence
      of Rab3a, a small GTPase that recruits rabphilin to synaptic vesicles. The rapid
      phosphorylation and dephosphorylation during and after stimulation demonstrates
      the transient nature of the modification. Our results indicate that rabphilin is
      phosphorylated on synaptic vesicles by Ca(2+)-dependent kinases that become
      active in synaptic terminals during exocytosis. We have found that
      phosphorabphilin has a reduced affinity for membranes; we therefore propose that
      the modulation of the membrane association of rabphilin has a role in the
      synaptic vesicle life cycle, perhaps in vesicle mobilization in preparation for
      subsequent rounds of neurotransmission.

PMID- 11466419
TI  - Arg3.1/Arc mRNA induction by Ca2+ and cAMP requires protein kinase A and mitogen
      activated protein kinase/extracellular regulated kinase activation.
AB  - Long-term potentiation (LTP) is a cellular model for persistent synaptic
      plasticity in the mammalian brain. Like several forms of memory, long-lasting LTP
      requires cAMP-mediated activation of protein kinase A (PKA) and is dependent on
      gene transcription. Consequently, activity-dependent genes such as c-fos that
      contain cAMP response elements (CREs) in their 5' regulatory region have been
      studied intensely. More recently, arg3.1/arc became of interest, because after
      synaptic stimulation, arg3.1/arc mRNA is rapidly induced and distributed to
      dendritic processes and may be locally translated there to facilitate synapse
      specific modifications. However, to date nothing is known about the signaling
      mechanisms involved in the induction of this gene. Here we report that arg3.1/arc
      is robustly induced with LTP stimulation even at intensities that are not
      sufficient to activate c-fos expression. Unlike c-fos, the 5' regulatory region
      of arg3.1/arc does not contain a CRE consensus sequence and arg3.1/arc is
      unresponsive to cAMP in NIH3T3 and Neuro2a cells. However, in PC12 cells and
      primary cultures of hippocampal neurons, arg3.1/arc can be induced by cAMP and
      calcium. This induction requires the activity of PKA and mitogen-activated
      protein kinase, suggesting a neuron-specific pathway for the activation of
      arg3.1/arc expression.

PMID- 11466420
TI  - Vulnerability of 125I-alpha-conotoxin MII binding sites to nigrostriatal damage
      in monkey.
AB  - Parkinson's disease, a neurodegenerative movement disorder characterized by
      selective degeneration of nigrostriatal dopaminergic neurons, affects
      approximately 1% of the population over 50. Because nicotinic acetylcholine
      receptors (nAChRs) may represent an important therapeutic target for this
      disorder, we performed experiments to elucidate the subtypes altered with
      nigrostriatal damage in parkinsonian monkeys. For this purpose we used (125)I
      alpha-conotoxin MII (CtxMII), a relatively new ligand that identifies alpha3
      and/or alpha6 subunits containing nAChR subtypes. In brain from untreated
      monkeys, there was saturable (125)I-alpha-CtxMII binding to a single population
      of high-affinity nicotinic sites (K(d) = 0.9 nm), primarily localized in the
      visual, habenula-interpeduncular, and nigrostriatal-mesolimbic pathways.
      Administration of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine resulted in damage to the nigrostriatal system and
      parkinsonism. Autoradiographic analysis showed that (125)I-alpha-CtxMII sites
      were selectively reduced (>/=99%) in the basal ganglia and that the lesion
      induced decreases correlated well with declines in the dopamine transporter, a
      marker of dopaminergic neuron integrity. These findings may indicate that most or
      all of (125)I-alpha-CtxMII-labeled nAChR subtypes in the basal ganglia are
      present on nigrostriatal dopaminergic neurons, in contrast to (125)I-epibatidine
      sites. These data suggest that the development of ligands directed to nAChR
      subtypes containing alpha3 and/or alpha6 subunits may yield a novel treatment
      strategy for parkinsonian patients with nigrostriatal dopaminergic degeneration.

PMID- 11466421
TI  - Subunit heterogeneity of cytoplasmic dynein: Differential expression of 14 kDa
      dynein light chains in rat hippocampus.
AB  - Cytoplasmic dynein is a multi-subunit protein complex in which each subunit is
      encoded by a few genes. How these subunit isoforms are assembled and regulated to
      mediate the diverse functions of cytoplasmic dynein is unknown. We previously
      have shown that two highly conserved 14 kDa dynein light chains, Tctex-1 and RP3,
      have different cargo-binding abilities. In this report, coimmunoprecipitation
      revealed that Tctex-1 and RP3 were present in mutually exclusive dynein complexes
      of brain. Two specific antibodies were used to examine the localization of these
      two dynein light chains in adult rat hippocampal formation and cerebral cortex.
      By light microscopy, Tctex-1 and RP3 immunoreactivities exhibited distinct and
      almost complementary distribution patterns in both brain regions. In hippocampal
      formation, Tctex-1 immunoreactivity was most enriched in somata of newly
      generated granule cells and scant in the mature granule and pyramidal cell
      somata. In contrast, RP3 immunoreactivity was abundant in pyramidal and granule
      cell somata. Ultrastructural analysis of the dentate gyrus revealed both dynein
      light chains were associated with various membranous organelles that often were
      affiliated with microtubules. In addition, Tctex-1 and RP3 immunoreactivities
      were preferentially and highly enriched on membranous organelles and/or vesicles
      of axon terminals and dendritic spines, respectively. These results suggest that
      dynein complexes with different subunit composition, and possibly function, are
      expressed differentially in a spatially and temporally regulated manner.
      Furthermore, Tctex-1 and RP3 may play important roles in synaptic functions.

PMID- 11466422
TI  - The p38 mitogen-activated protein kinase is involved in associative learning in
      rabbits.
AB  - This study examined the role of the mitogen-activated protein kinase (MAPK)
      family during acquisition of the rabbit's classically conditioned eye-blink
      response. Eye-blink conditioning produced a significant, bilateral activation of
      both extracellular signal-regulated protein kinases (ERKs) and p38 MAPK in the
      anterior cerebellar vermis. There was also a significant bilateral activation of
      ERKs in the dorsal hippocampus with no change in p38 MAPK. These changes were
      seen at 2 min after the last conditioning session, were maintained for at least
      180 min, and occurred without any change in the protein expression of either ERKs
      or p38 MAPK. There were no changes in ERKs or p38 MAPK in frontal cortex, in
      cerebellar hemispheral lobule VI, or in a section of brainstem containing the
      inferior olive. Moreover, the stress-related protein kinase Jun N-terminal kinase
      (JNK), another subfamily of MAPKs, was not altered in any of the brain regions
      examined. Animals receiving explicitly unpaired presentations of a conditioned
      stimulus and an unconditioned stimulus did not acquire conditioned responses
      (CRs) and did not demonstrate any changes in ERKs, p38 MAPK, or JNK. The
      intraventricular injection of SB203580, a selective p38 MAPK inhibitor,
      significantly retarded CR acquisition and blocked the learning-related increases
      in p38 MAPK activity in the anterior vermis. PD98059, a selective MAPK kinase
      inhibitor, had a smaller and only marginally significant effect on CR
      acquisition, although it did block the learning-related increases in ERK activity
      in both the hippocampus and anterior vermis. These results indicate that p38 MAPK
      is activated during associative learning and may play a role in the
      transcriptional events that lead to memory consolidation.

PMID- 11466423
TI  - Impairment of mossy fiber long-term potentiation and associative learning in
      pituitary adenylate cyclase activating polypeptide type I receptor-deficient
      mice.
AB  - The pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor
      (PAC1) is a G-protein-coupled receptor binding the strongly conserved
      neuropeptide PACAP with 1000-fold higher affinity than the related peptide
      vasoactive intestinal peptide. PAC1-mediated signaling has been implicated in
      neuronal differentiation and synaptic plasticity. To gain further insight into
      the biological significance of PAC1-mediated signaling in vivo, we generated two
      different mutant mouse strains, harboring either a complete or a forebrain
      specific inactivation of PAC1. Mutants from both strains show a deficit in
      contextual fear conditioning, a hippocampus-dependent associative learning
      paradigm. In sharp contrast, amygdala-dependent cued fear conditioning remains
      intact. Interestingly, no deficits in other hippocampus-dependent tasks modeling
      declarative learning such as the Morris water maze or the social transmission of
      food preference are observed. At the cellular level, the deficit in hippocampus
      dependent associative learning is accompanied by an impairment of mossy fiber
      long-term potentiation (LTP). Because the hippocampal expression of PAC1 is
      restricted to mossy fiber terminals, we conclude that presynaptic PAC1-mediated
      signaling at the mossy fiber synapse is involved in both LTP and hippocampus
      dependent associative learning.

PMID- 11466424
TI  - Role of IL-1alpha and IL-1beta in ischemic brain damage.
AB  - The cytokine interleukin-1 (IL-1) has been strongly implicated in the
      pathogenesis of ischemic brain damage. Evidence to date suggests that the major
      form of IL-1 contributing to ischemic injury is IL-1beta rather than IL-1alpha,
      but this has not been tested directly. The objective of the present study was to
      compare the effects of transient cerebral ischemia [30 min middle cerebral artery
      occlusion (MCAO)] on neuronal injury in wild-type (WT) mice and in IL-1alpha, IL
      1beta, or both IL-1alpha and IL-1beta knock-out (KO) mice. Mice lacking both
      forms of IL-1 exhibited dramatically reduced ischemic infarct volumes compared
      with wild type (total volume, 70%; cortex, 87% reduction). Ischemic damage
      compared with WT mice was not significantly altered in mice lacking either IL
      1alpha or IL-1beta alone. IL-1beta mRNA, but not IL-1alpha or the IL-1 type 1
      receptor, was strongly induced by MCAO in WT and IL-1alpha KO mice.
      Administration (intracerebroventricularly) of recombinant IL-1 receptor
      antagonist significantly reduced infarct volume in WT (-32%) and IL-1alpha KO (
      48%) mice, but had no effect on injury in IL-1beta or IL-1alpha/beta KO mice.
      These data confirm that IL-1 plays a major role in ischemic brain injury. They
      also show that chronic deletion of IL-1alpha or IL-1beta fails to influence brain
      damage, probably because of compensatory changes in the IL-1 system in IL-1alpha
      KO mice and changes in IL-1-independent mediators of neuronal death in IL-1beta
      KO mice.

PMID- 11466425
TI  - Activation of expressed KCNQ potassium currents and native neuronal M-type
      potassium currents by the anti-convulsant drug retigabine.
AB  - Retigabine [D-23129; N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid
      ethyl ester] is a novel anticonvulsant compound that is now in clinical phase II
      development. It has previously been shown to enhance currents generated by
      KCNQ2/3 K(+) channels when expressed in Chinese hamster ovary (CHO) cells (Main
      et al., 2000; Wickenden et al., 2000). In the present study, we have compared the
      actions of retigabine on KCNQ2/3 currents with those on currents generated by
      other members of the KCNQ family (homomeric KCNQ1, KCNQ2, KCNQ3, and KCNQ4
      channels) expressed in CHO cells and on the native M current in rat sympathetic
      neurons [thought to be generated by KCNQ2/3 channels (Wang et al., 1998)].
      Retigabine produced a hyperpolarizing shift of the activation curves for KCNQ2/3,
      KCNQ2, KCNQ3, and KCNQ4 currents with differential potencies in the following
      order: KCNQ3 > KCNQ2/3 > KCNQ2 > KCNQ4, as measured either by the maximum
      hyperpolarizing shift in the activation curves or by the EC(50) values. In
      contrast, retigabine did not enhance cardiac KCNQ1 currents. Retigabine also
      produced a hyperpolarizing shift in the activation curve for native M channels in
      rat sympathetic neurons. The retigabine-induced current was inhibited by
      muscarinic receptor stimulation, with similar agonist potency but 25% reduced
      maximum effect. In unclamped neurons, retigabine produced a hyperpolarization and
      reduced the number of action potentials produced by depolarizing current
      injections, without change in action potential configuration.

PMID- 11466426
TI  - Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors
      to the postsynaptic membrane.
AB  - Recent work has shown substantial alterations in NMDA receptor subunit
      expression, assembly, and phosphorylation in the dopamine-depleted striatum of a
      rodent 6-hydroxydopamine model of Parkinson's disease. These modifications are
      hypothesized to result from the trafficking of NMDA receptors between subcellular
      compartments. Here we show that in rat striatal tissues the NR2A and NR2B
      subunits in the synaptosomal membrane, and not those in the light membrane and
      synaptic vesicle-enriched compartments, are tyrosine phosphorylated. The dopamine
      D1 receptor agonist SKF-82958 produces (1) an increase in NR1, NR2A, and NR2B
      proteins in the synaptosomal membrane fraction; (2) a decrease in NR1, NR2A, and
      NR2B proteins in the light membrane and synaptic vesicle-enriched fractions; and
      (3) an increase in the tyrosine phosphorylation of NR2A and NR2B in the
      synaptosomal membrane compartment. The protein phosphatase inhibitor pervanadate
      reproduces the alterations in subcellular distribution and phosphorylation,
      whereas the effects of the dopamine D1 receptor agonist are blocked by genistein,
      a protein tyrosine kinase inhibitor. Dopamine D1 receptor agonist treatment does
      not change the subcellular distribution of the AMPA receptor subunits GluR1 or
      GluR2/3 in the striatum and has no effect on cortical or cerebellar NMDA receptor
      subunits. These data reveal a rapid dopamine D1 receptor- and tyrosine kinase
      dependent trafficking of striatal NMDA receptors between intracellular and
      postsynaptic sites. The subcellular trafficking of striatal NMDA receptors may
      play a significant role both in the pathogenesis of Parkinson's disease and in
      the development of adverse effects of chronic dopaminergic therapy in
      parkinsonian patients.

PMID- 11466427
TI  - Neuronal expression of an FMRFamide-gated Na+ channel and its modulation by acid
      pH.
AB  - The molluscan Phe-Met-Arg-Phe-amide (FMRFamide)-gated sodium channels (FaNaCs)
      show both structural and functional similarities to the mammalian acid-sensing
      ion channels (ASICs). Both channel types are related to the epithelial sodium
      channels and, although the neuropeptide FMRFamide directly gates the FaNaCs, it
      also modulates the proton-gating properties of ASICs. It is not yet known whether
      protons can alter the gating properties of the FaNaCs. We chose to examine this
      possibility at a site of FaNaC expression in the nervous system of the mollusk
      Lymnaea stagnalis. We cloned a putative L. stagnalis FaNaC (LsFaNaC) that
      exhibited a high degree of sequence identity to the Helix aspersa FaNaC (HaFaNaC,
      60%), and a weaker homology to the ASICs (ASIC3, 22%). In situ hybridization was
      used to map the LsFaNaC expression pattern in the brain and to identify the right
      pedal giant1 (RPeD1) neuron as a site where the properties of the endogenous
      channel could be studied. In RPeD1 neurons isolated in culture, we demonstrated
      the presence of an FMRFamide-gated sodium current with features expected for a
      FaNaC: amiloride sensitivity, sodium selectivity, specificity for FMRFamide and
      Phe-Leu-Arg-Phe-amide (FLRFamide), and no dependency on G-protein coupling. The
      sodium current also exhibited rapid desensitization in response to repeated
      FMRFamide applications. Lowering of the pH of the bathing solution reduced the
      amplitude of the FMRFamide-gated inward current, while also activating an
      additional sustained weak inward current that was apparently not mediated by the
      FaNaC. Acidification also prevented the desensitization of the FMRFamide-induced
      inward current. The acid sensitivity of LsFaNaC is consistent with the hypothesis
      that FaNaCs share a common ancestry with the ASICs.

PMID- 11466428
TI  - Associative learning elicits the formation of multiple-synapse boutons.
AB  - The formation of new synapses has been suggested to underlie learning and memory.
      However, previous work from this laboratory has demonstrated that hippocampus
      dependent associative learning does not induce a net gain in the total number of
      hippocampal synapses and, hence, a net synaptogenesis. The aim of the present
      work was to determine whether associative learning involves a specific
      synaptogenesis confined to the formation of multiple-synapse boutons (MSBs) that
      synapse with more than one dendritic spine. We used the behavioral paradigm of
      trace eyeblink conditioning, which is a hippocampus-dependent form of associative
      learning. Conditioned rabbits were given daily 80-trial sessions to a criterion
      of 80% conditioned responses in a session. During each trial, the conditioned
      stimulus (tone) and the unconditioned stimulus (corneal airpuff) were presented
      with an intervening trace interval of 500 msec. Brain tissue was taken for
      morphological analyses 24 hr after the last session. Unbiased stereological
      methods were used for obtaining estimates of the total number of MSBs in the
      stratum radiatum of hippocampal subfield CA1. The results showed that the total
      number of MSBs was significantly increased in conditioned rabbits as compared
      with pseudoconditioned or unstimulated controls. This conditioning-induced
      change, which occurs without a net synaptogenesis, reflects a specific
      synaptogenesis resulting in MSB formation. Models of the latter process are
      proposed. The models postulate that it requires spine motility and may involve
      the relocation of existing spines from nonactivated boutons or the outgrowth of
      newly formed spines for specific synaptogenesis with single-synapse boutons
      activated by the conditioning stimulation.

PMID- 11466429
TI  - Subunit interactions and AMPA receptor desensitization.
AB  - Most AMPA-type glutamate receptors (GluRs) exhibit rapid and virtually complete
      desensitization when activated by glutamate, and at some central synapses it is
      largely desensitization that determines the decay of EPSCs. However, the
      mechanisms underlying the conformation change that results in desensitization are
      not fully understood. AMPA receptor subunits that contain a single amino acid
      substitution have been shown to form homomeric channels that show markedly
      reduced desensitization. We show here that the coexpression of wild-type GluR1
      with one such mutant, GluR1(L497Y), results in heteromeric channels that show
      desensitization behavior that is intermediate between wild-type and mutant
      homomers. The relative amplitudes of the multiple exponential components present
      in the decay of glutamate-evoked currents depended on the relative abundance of
      wild-type and mutant subunits and were described by the combinatorial
      distribution of the two types of subunits into tetrameric, but not pentameric,
      assemblies. Our results are consistent with recent structural data suggesting
      that AMPA receptors are tetrameric assemblies composed of two dimers.

PMID- 11466430
TI  - Interactions between fibroblast growth factors and Notch regulate neuronal
      differentiation.
AB  - The differentiation of precursor cells into neurons has been shown to be
      influenced by both the Notch signaling pathway and growth factor stimulation. In
      this study, the regulation of neuronal differentiation by these mechanisms was
      examined in the embryonic day 10 neuroepithelial precursor (NEP) population. By
      downregulating Notch1 expression and by the addition of a Delta1 fusion protein
      (Delta Fc), it was shown that signaling via the Notch pathway inhibited neuron
      differentiation in the NEP cells, in vitro. The expression of two of the Notch
      receptor homologs, Notch1 and Notch3, and the ligand Delta1 in these NEP cells
      was found to be influenced by a number of different growth factors, indicating a
      potential interaction between growth factors and Notch signaling. Interestingly,
      none of the growth factors examined promoted neuron differentiation; however, the
      fibroblast growth factors (FGFs) 1 and 2 potently inhibited differentiation. FGF1
      and FGF2 upregulated the expression of Notch and decreased expression of Delta1
      in the NEP cells. In addition, the inhibitory response of the cells to the FGFs
      could be overcome by downregulating Notch1 expression and by disrupting Notch
      cleavage and signaling by the ablation of the Presenilin1 gene. These results
      indicate that FGF1 and FGF2 act via the Notch pathway, either directly or
      indirectly, to inhibit differentiation. Thus, signaling through the Notch
      receptor may be a common regulator of neuronal differentiation within the
      developing forebrain.

PMID- 11466431
TI  - Functional implications of neurotransmitter expression during axonal
      regeneration: serotonin, but not peptides, auto-regulate axon growth of an
      identified central neuron.
AB  - We studied the regenerative properties of one of two electrically coupled
      molluscan neurons, the serotonergic cerebral giant cells (CGCs) of Lymnaea
      stagnalis, after axotomy. The CGCs play a crucial role in feeding behavior, and
      when both cells are disconnected from their target neurons, animals no longer
      feed. When one CGC was permanently disconnected from its targets and the other
      was reversibly damaged by a nerve crush, the latter one regenerated over a period
      of 2 weeks to reform functional synapses with specific target neurons. At the
      same time, recovery of the feeding behavior was observed. After the crush,
      neuropeptide gene expression in the CGC was downregulated to approximately 50%.
      Serotonin synthesis, on the other hand, remained unaffected, suggesting that
      serotonin might have an active role in regeneration. In primary neuron culture,
      CGCs failed to extend neurites in the presence of serotonin; in cells that
      extended neurites in the absence of serotonin, focally applied serotonin, but not
      neuropeptides, induced growth cone collapse. Using serotonin-sensitive sniffer
      cells, we show that CGC neurites and growth cones release serotonin in culture.
      Finally, both the spontaneous and stimulation-induced release of serotonin from
      CGCs in culture resulted in growth cone collapse responses that could be blocked
      by the serotonin receptor antagonist methysergide. Our data suggest that auto
      released serotonin is inhibitory to CGC neurite outgrowth in vitro. During
      regeneration in vivo, serotonin release might fine-tune axon guidance and
      branching by inducing local collapse responses in extending neurites.

PMID- 11466432
TI  - Development of layer I neurons in the primate cerebral cortex.
AB  - Layer I, which plays an important role in the development of the cerebral cortex,
      expands in size and diversity in primates. We found that, unlike in rodents, in
      the macaque monkey, neurons of this layer are generated during the entire 2 month
      period of corticogenesis, within the middle of the 165-d-long gestation. The
      large, classical Cajal-Retzius cells, immunoreactive to reelin and calretinin but
      not to GABA, are generated first [embryonic day 38 (E38)-E50], with the peak of
      [(3)H]thymidine ([(3)H]TdR) labeling at E43. Ultrastructural analysis revealed
      that processes of these cells form a stereotyped, rectangular network oriented
      parallel to the pial surface. Genesis of smaller, GABAergic neurons begins
      slightly later (E43), reaches a peak of [(3)H]TdR labeling between E54 and E70,
      and continues until the completion of corticogenesis (E94). These late-generated
      layer I cells are imported from outside sources such as the olfactory primordium
      and ganglionic eminence and via a massive subpial granular layer that may also
      supply some GABAergic interneurons to the subjacent cortical plate. The ratio of
      large-to-small layer I neurons changes differentially, indicating that each class
      is produced and/or eliminated at a different rate and suggesting that their roles
      in primates are diverse.

PMID- 11466433
TI  - Neurotrophin-3 is required for the survival-differentiation of subsets of
      developing enteric neurons.
AB  - Neurotrophin-3 (NT-3) promotes enteric neuronal development in vitro;
      nevertheless, an enteric nervous system (ENS) is present in mice lacking NT-3 or
      TrkC. We thus analyzed the physiological significance of NT-3 in ENS development.
      Subsets of neurons developing in vitro in response to NT-3 became NT-3 dependent;
      NT-3 withdrawal led to apoptosis, selectively in TrkC-expressing neurons.
      Antibodies to NT-3, which blocked the developmental response of enteric crest
      derived cells to exogenous NT-3, did not inhibit neuronal development in cultures
      of isolated crest-derived cells but did so in mixed cultures of crest- and non
      neural crest-derived cells; therefore, the endogenous NT-3 that supports enteric
      neuronal development is probably obtained from noncrest-derived mesenchymal
      cells. In mature animals, retrograde transport of (125)I-NT-3, injected into the
      mucosa, labeled neurons in ganglia of the submucosal but not myenteric plexus;
      injections of (125)I-NT-3 into myenteric ganglia, the tertiary plexus, and
      muscle, labeled neurons in underlying submucosal and distant myenteric ganglia.
      The labeling pattern suggests that NT-3-dependent submucosal neurons may be
      intrinsic primary afferent and/or secretomotor, whereas NT-3-dependent myenteric
      neurons innervate other myenteric ganglia and/or the longitudinal muscle.
      Myenteric neurons were increased in number and size in transgenic mice that
      overexpress NT-3 directed to myenteric ganglia by the promoter for dopamine beta
      hydroxylase. The numbers of neurons were regionally reduced in both plexuses in
      mice lacking NT-3 or TrkC. A neuropoietic cytokine (CNTF) interacted with NT-3 in
      vitro, and if applied sequentially, compensated for NT-3 withdrawal. These
      observations indicate that NT-3 is required for the normal development of the
      ENS.

PMID- 11466434
TI  - Generation of a novel functional neuronal circuit in Hoxa1 mutant mice.
AB  - Early organization of the vertebrate brainstem is characterized by cellular
      segmentation into compartments, the rhombomeres, which follow a metameric pattern
      of neuronal development. Expression of the homeobox genes of the Hox family
      precedes rhombomere formation, and analysis of mouse Hox mutations revealed that
      they play an important role in the establishment of rhombomere-specific neuronal
      patterns. However, segmentation is a transient feature, and a dramatic
      reconfiguration of neurons and synapses takes place during fetal and postnatal
      stages. Thus, it is not clear whether the early rhombomeric pattern of Hox
      expression has any influence on the establishment of the neuronal circuitry of
      the mature brainstem. The Hoxa1 gene is the earliest Hox gene expressed in the
      developing hindbrain. Moreover, it is rapidly downregulated. Previous analysis of
      mouse Hoxa1(-/-) mutants has focused on early alterations of hindbrain
      segmentation and patterning. Here, we show that ectopic neuronal groups in the
      hindbrain of Hoxa1(-/-) mice establish a supernumerary neuronal circuit that
      escapes apoptosis and becomes functional postnatally. This system develops from
      mutant rhombomere 3 (r3)-r4 levels, includes an ectopic group of progenitors with
      r2 identity, and integrates the rhythm-generating network controlling respiration
      at birth. This is the first demonstration that changes in Hox expression patterns
      allow the selection of novel neuronal circuits regulating vital adaptive
      behaviors. The implications for the evolution of brainstem neural networks are
      discussed.

PMID- 11466435
TI  - Asymmetric segregation of Numb in retinal development and the influence of the
      pigmented epithelium.
AB  - Asymmetric segregation of cell-fate determinants during cytokinesis plays an
      important part in controlling cell-fate choice in invertebrates. During
      Drosophila neurogenesis, for example, asymmetric segregation of the Numb protein,
      which inhibits Notch signaling, is necessary for the two daughter cells of a
      division to have different fates. In vertebrates, the role of asymmetric
      segregation of cell-fate determinants is uncertain, and the way the process might
      be regulated is unknown. We have studied the orientation of cell divisions and
      the distribution of Numb in the developing rat retina. We show that, whereas most
      retinal neuroepithelial cells divide with their mitotic spindles oriented
      parallel to the plane of the neuroepithelium, a substantial minority divides with
      their spindles oriented perpendicularly. The proportion of these vertically
      dividing cells changes during development, peaking around the day of birth. Numb
      appears to be inherited only by the apical daughter cell when a neuroepithelial
      cell divides vertically. Similarly, in dissociated cell cultures, some retinal
      neuroepithelial cells divide asymmetrically and distribute Numb to only one of
      the two daughter cells, suggesting that the dissociated cells can retain their
      polarity in vitro. Using retinal explant cultures, we find that the retinal
      pigment epithelium apparently promotes vertical divisions in the neural retina.
      To our knowledge, this is the first evidence that asymmetric segregation of cell
      fate determinants may contribute to cell diversification in the mammalian retina
      and that an epithelium controls this process by influencing the plane of division
      in the adjacent neural retina.

PMID- 11466436
TI  - Target-dependent sexual differentiation of a limbic-hypothalamic neural pathway.
AB  - Neural pathways between sexually dimorphic forebrain regions develop under the
      influence of sex steroid hormones during the perinatal period, but how these
      hormones specify precise sex-specific patterns of connectivity is unknown. A
      heterochronic coculture system was used to demonstrate that sex steroid hormones
      direct development of a sexually dimorphic limbic-hypothalamic neural pathway
      through a target-dependent mechanism. Explants of the principal nucleus of the
      bed nuclei of the stria terminalis (BSTp) extend neurites toward explants of the
      anteroventral periventricular nucleus (AVPV) derived from male but not female
      rats. Coculture of BSTp explants from male rats with AVPV explants derived from
      females treated in vivo with testosterone for 9 d resulted in a high density of
      neurites extending from the BSTp to the AVPV explant, as was the case when the
      BSTp explants were derived from females and the AVPV explants were derived from
      males or androgen-treated females. These in vitro findings suggest that during
      the postnatal period testosterone induces a target-derived, diffusible
      chemotropic activity that results in a sexually dimorphic pattern of
      connectivity.

PMID- 11466437
TI  - Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance
      excitatory synaptic transmission in GABAergic interneurons of the hippocampus.
AB  - Neuregulins are highly expressed in the CNS, especially in cholinergic neurons.
      We have examined the effect of neuregulin on nicotinic acetylcholine receptors
      (nAChRs) in neurons dissociated from the rat hippocampus. Rapid application of
      acetylcholine (ACh) induced a rapidly rising and decaying inward current in some
      of the neurons, which was completely blocked by methyllycaconitine, a specific
      antagonist of the alpha7 subunit of the nAChR. When the cells were treated with 5
      nm neuregulin (NRG1-beta1) for 2-4 d, a twofold increase in amplitude of the peak
      ACh-induced current was observed, and there was a comparable increase in (125)I
      alpha-bungarotoxin binding. The fast ACh-induced peak current was prominent in
      large neurons that also contained GABA immunoreactivity. These presumptive
      GABAergic neurons constituted approximately 10% of neurons present in 7- to 9-d
      old cultures. In addition to the large inward peak current, ACh also evoked
      transmitter release from presynaptic nerve terminals. Pharmacologic experiments
      indicated that the shower of PSCs was mediated by glutamate, with a small
      minority caused by the action of GABA. Chronic exposure to NRG1-beta1 increased
      the amplitude of ACh-evoked PSCs but not the minimum "quantal" PSC. NRG1-beta1
      also increased the percentage of neurons that exhibited ACh-evoked PSCs.

PMID- 11466438
TI  - P2X3 knock-out mice reveal a major sensory role for urothelially released ATP.
AB  - The present study explores the possible involvement of a purinergic mechanism in
      mechanosensory transduction in the bladder using P2X(3) receptor knock-out
      (P2X(3)-/-) and wild-type control (P2X(3)+/+) mice. Immunohistochemistry revealed
      abundant nerve fibers in a suburothelial plexus in the mouse bladder that are
      immunoreactive to anti-P2X(3). P2X(3)-positive staining was completely absent in
      the subepithelial plexus of the P2X(3)-/- mice, whereas staining for calcitonin
      gene-related peptide and vanilloid receptor 1 receptors remained. Using a novel
      superfused mouse bladder-pelvic nerve preparation, we detected a release of ATP
      proportional to the extent of bladder distension in both P2X(3)+/+ and P2X(3)-/-
      mice, although P2X(3)-/- bladder had an increased capacity compared with that of
      the P2X(3)+/+ bladder. The activity of multifiber pelvic nerve afferents
      increased progressively during gradual bladder distension (at a rate of 0.1
      ml/min). However, the bladder afferents from P2X(3)-/- mice showed an attenuated
      response to bladder distension. Mouse bladder afferents of P2X(3)+/+, but not
      P2X(3)-/-, were rapidly activated by intravesical injections of P2X agonists (ATP
      or alpha,beta-methylene ATP) and subsequently showed an augmented response to
      bladder distension. By contrast, P2X antagonists [2',3'-O-(2,4,6-trinitrophenyl)
      ATP and pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid] and capsaicin
      attenuated distension-induced discharges in bladder afferents. These data
      strongly suggest a major sensory role for urothelially released ATP acting via
      P2X(3) receptors on a subpopulation of pelvic afferent fibers.

PMID- 11466439
TI  - Circulating insulin-like growth factor I mediates the protective effects of
      physical exercise against brain insults of different etiology and anatomy.
AB  - Physical exercise ameliorates age-related neuronal loss and is currently
      recommended as a therapeutical aid in several neurodegenerative diseases.
      However, evidence is still lacking to firmly establish whether exercise
      constitutes a practical neuroprotective strategy. We now show that exercise
      provides a remarkable protection against brain insults of different etiology and
      anatomy. Laboratory rodents were submitted to treadmill running (1 km/d) either
      before or after neurotoxin insult of the hippocampus (domoic acid) or the
      brainstem (3-acetylpyridine) or along progression of inherited neurodegeneration
      affecting the cerebellum (Purkinje cell degeneration). In all cases, animals show
      recovery of behavioral performance compared with sedentary ones, i.e., intact
      spatial memory in hippocampal-injured mice, and normal or near to normal motor
      coordination in brainstem- and cerebellum-damaged animals. Furthermore, exercise
      blocked neuronal impairment or loss in all types of injuries. Because circulating
      insulin-like growth factor I (IGF-I), a potent neurotrophic hormone, mediates
      many of the effects of exercise on the brain, we determined whether
      neuroprotection by exercise is mediated by IGF-I. Indeed, subcutaneous
      administration of a blocking anti-IGF-I antibody to exercising animals to inhibit
      exercise-induced brain uptake of IGF-I abrogates the protective effects of
      exercise in all types of lesions; antibody-treated animals showed sedentary-like
      brain damage. These results indicate that exercise prevents and protects from
      brain damage through increased uptake of circulating IGF-I by the brain. The
      practice of physical exercise is thus strongly recommended as a preventive
      measure against neuronal demise. These findings also support the use of IGF-I as
      a therapeutical aid in brain diseases coursing with either acute or progressive
      neuronal death.

PMID- 11466440
TI  - Recurrent network interactions underlying flow-field selectivity of visual
      interneurons.
AB  - Motion-sensitive large-field neurons found at higher processing stages in many
      species often exhibit a remarkable selectivity for particular flow fields.
      However, the underlying neural mechanisms are not yet understood. We studied this
      problem in the so-called lobula plate tangential cells (LPTCs) of the fly.
      Investigating the connectivity between LPTCs by means of dual recordings, we find
      two types of connections: (1) heterolateral connections between LPTCs of both
      hemispheres and (2) ipsilateral connections between LPTCs within one lobula
      plate. The circuit is suitable to amplify incoming, dendritic signals in the case
      of rotatory flow fields and to reduce them in the case of other flow-field
      structures. In addition to feedforward connectivity, thus, the flow-field
      selectivity of LPTCs may be significantly attributable to recurrent excitation
      involving the network of large-field neurons in both brain hemispheres.

PMID- 11466441
TI  - Exploration of signal transduction pathways in cerebellar long-term depression by
      kinetic simulation.
AB  - Because multiple molecular signal transduction pathways regulate cerebellar long
      term depression (LTD), which is thought to be a possible molecular and cellular
      basis of cerebellar learning, the systematic relationship between cerebellar LTD
      and the currently known signal transduction pathways remains obscure. To address
      this issue, we built a new diagram of signal transduction pathways and developed
      a computational model of kinetic simulation for the phosphorylation of AMPA
      receptors, known as a key step for expressing cerebellar LTD. The phosphorylation
      of AMPA receptors in this model consists of an initial phase and an intermediate
      phase. We show that the initial phase is mediated by the activation of linear
      cascades of protein kinase C (PKC), whereas the intermediate phase is mediated by
      a mitogen-activated protein (MAP) kinase-dependent positive feedback loop pathway
      that is responsible for the transition from the transient phosphorylation of the
      AMPA receptors to the stable phosphorylation of the AMPA receptors. These phases
      are dually regulated by the PKC and protein phosphatase pathways. Both phases
      also require nitric oxide (NO), although NO per se does not show any ability to
      induce LTD; this is consistent with a permissive role as reported experimentally
      (Lev-Ram et al., 1997). Therefore, the kinetic simulation is a powerful tool for
      understanding and exploring the behaviors of complex signal transduction pathways
      involved in cerebellar LTD.

PMID- 11466442
TI  - Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic
      transmission and plasticity and causes memory deficits.
AB  - We injected a combination of the beta-amyloids (Abetas) Abeta40 and Abeta43 to
      "seed" formation of amyloid deposits in the dorsal dentate gyrus of rats in vivo,
      on the basis of a theory of Jarrett and Landsbury (1993). Rats were tested on
      several different learning tasks, and synaptic transmission and plasticity were
      assessed in vivo. Between 7 and 16 weeks after injection, we found aggregated
      amyloid material, reactive astrocytosis, microgliosis, and cell loss around the
      sites of injection. Rats were impaired specifically in working memory type tasks
      in accordance with the type of memory deficit observed in the early stages of
      Alzheimer's disease. Synaptic transmission and long-term potentiation, a
      candidate cellular mechanism for memory, were severely impaired in vivo.
      Injections of the same dose of fragments individually did not induce these
      effects. These findings suggest that aggregated amyloid material induces
      cognitive deficits similar to those observed in the early phases of Alzheimer's
      disease via an alteration in neuronal transmission and plasticity.

PMID- 11466443
TI  - Acquisition of eyeblink conditioning is critically dependent on normal function
      in cerebellar cortical lobule HVI.
AB  - Classical conditioning of the nictitating membrane response (NMR)/eyeblink
      response of rabbits is a simple form of cerebellar-dependent, associative motor
      learning. Reversible inactivations of the cerebellar nuclei and inferior olive
      have implicated the olivo-cortico-nuclear loop in the acquisition of nictitating
      membrane conditioning, but the role of the cerebellar cortex in acquisition has
      not been tested directly. Here we have used local infusions of the water-soluble,
      disodium salt of 6-cyano-7-nitroquinoxaline-2,3-dione reversibly to block
      cerebellar cortical AMPA/kainate receptors in lobule HVI during acquisition
      training. After the drug effects dissipated, there was no evidence that
      acquisition had taken place; the subjects behaved as if naive. Further training
      without inactivation then allowed normal acquisition, and further inactivations
      during performance of conditioned responses abolished these established
      responses. There was a strong correlation between the inactivation effects on
      acquisition and subsequent inactivation effects on performance, indicating that
      the same eyeblink-control cortical microzones are engaged in learning and
      expressing this behavior. The cortical component of the olivo-cortico-nuclear
      loop is essential for acquisition of classically conditioned nictitating membrane
      response learning, and eyeblink control areas in HVI are critical. Our findings
      are consistent with models of cerebellar learning that assign essential
      plasticity to the cortex or to a distribution between levels in olivo-cortico
      nuclear modules.

PMID- 11466444
TI  - Progesterone blockade of estrogen activation of mu-opioid receptors regulates
      reproductive behavior.
AB  - The mu-opioid receptor (MOR), a G-protein-coupled receptor, is internalized after
      endogenous agonist binding. Although receptor activation and internalization are
      separate events, internalization is a good assay for activation because
      endogenous opioid peptides all induce internalization. Estrogen treatment of
      ovariectomized rats induces MOR internalization, providing a neurochemical
      signature of estrogen activation of the medial preoptic nucleus. MOR activation
      appears to be the mechanism via which estrogen acts in the medial preoptic area
      to prevent the display of female reproductive behavior during the first 20-24 hr
      after estrogen treatment. Naltrexone, an alkaloid universal opioid receptor
      antagonist, prevented MOR internalization, suggesting that estrogen induces the
      release of endogenous opioid peptides that in turn activate the MOR. Enkephalins
      and beta-endorphin are nonselective endogenous MOR ligands. The most selective
      endogenous MOR ligands are the endomorphins. Infusions of selective MOR agonists,
      H-Tyr-d-Ala-Gly-N-Met-Phe-glycinol-enkephalin (DAMGO) or endomorphin-1, into the
      medial preoptic nucleus attenuated lordosis, and their effects were blocked with
      the MOR antagonist H-d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP). Infusion
      of endomorphin-1 internalized MOR. To determine whether progestin also acts via
      the MOR system to facilitate reproductive behavior, ovariectomized rats were
      primed with 17beta-estradiol and progesterone. Progestin facilitation of lordosis
      was correlated with a reduction of estrogen-induced MOR internalization.
      Progestin reversed estrogen-induced MOR internalization, suggesting that
      progesterone blocked estrogen-induced endogenous opioid release, relieving
      estrogen inhibition and facilitating lordosis. These results indicate a central
      role of MOR in the mediation of sex steroid activation of the CNS to regulate
      female reproductive behavior.

PMID- 11466445
TI  - Reward unpredictability inside and outside of a task context as a determinant of
      the responses of tonically active neurons in the monkey striatum.
AB  - Tonically active neurons (TANs) in the monkey striatum are involved in detecting
      motivationally relevant stimuli. We recently provided evidence that the timing of
      conditioned stimuli strongly influences the responsiveness of TANs, the source of
      which is likely to be the monkey's previous experience with particular temporal
      regularities in sequential task events. To extend these findings, we investigated
      the relationship of TAN responses to a primary liquid reward, the timing of which
      is more or less predictable to the monkey either outside of a task or during
      instrumental task performance. Reward predictability was indexed by the timing
      characteristics of the mouth movements. The responsiveness of TANs to reward
      increased with the range and variability of time periods before reward, notably
      when the liquid was delivered outside of a task. A change in the temporal order
      of events in a task context produced an increase of response to reward,
      suggesting an influence of the predicted nature of the event in addition to its
      time of occurrence. By contrast, we observed no substantial changes in neuronal
      activity at the expected time of reward when this event failed to occur,
      suggesting that these neurons do not appear to carry information about an error
      in reward prediction. These results demonstrate that TANs constitute a neuronal
      system that is involved in detecting unpredicted reward events, irrespective of
      the specific behavioral situation in which such events occur. The responses
      influenced by stimulus prediction may constitute a neuronal basis for the notion
      that striatal processing is crucial for habit learning.

PMID- 11466446
TI  - Neural correlates for angular head velocity in the rat dorsal tegmental nucleus.
AB  - Many neurons in the rat lateral mammillary nuclei (LMN) fire selectively in
      relation to the animal's head direction (HD) in the horizontal plane independent
      of the rat's location or behavior. One hypothesis of how this representation is
      generated and updated is via subcortical projections from the dorsal tegmental
      nucleus (DTN). Here we report the type of activity in DTN neurons. The majority
      of cells (75%) fired as a function of the rat's angular head velocity (AHV).
      Cells exhibited one of two types of firing patterns: (1) symmetric, in which the
      firing rate was positively correlated with AHV during head turns in both
      directions, and (2) asymmetric, in which the firing rate was positively
      correlated with head turns in one direction and correlated either negatively or
      not at all in the opposite direction. In addition to modulation by AHV, some of
      the AHV cells (40.1%) were weakly modulated by the rat's linear velocity, and a
      smaller number were modulated by HD (11%) or head pitch (15.9%). Autocorrelation
      analyses indicated that with the head stationary, AHV cells displayed irregular
      discharge patterns. Because afferents from the DTN are the major source of
      information projecting to the LMN, these results suggest that AHV information
      from the DTN plays a significant role in generating the HD signal in LMN. A model
      is proposed showing how DTN AHV cells can generate and update the LMN HD cell
      signal.

PMID- 11466447
TI  - Behavioral properties of the trigeminal somatosensory system in rats performing
      whisker-dependent tactile discriminations.
AB  - To address several fundamental questions regarding how multiwhisker tactile
      stimuli are integrated and processed by the trigeminal somatosensory system, a
      novel behavioral task was developed that required rats to discriminate the width
      of either a wide or narrow aperture using only their large mystacial vibrissae.
      Rats quickly acquired this task and could accurately discriminate between
      apertures of very similar width. Accurate discriminations required a large number
      of intact facial whiskers. Systematic removal of individual whiskers caused a
      decrease in performance that was directly proportional to the number of whiskers
      removed, indicating that tactile information from multiple whiskers is integrated
      as rats gauge aperture width. In different groups of rats, different sets of
      whiskers were removed in patterns that preferentially left whisker rows or
      whisker arcs intact. These different whisker removals caused similar decreases in
      performance, indicating that individual whiskers within the vibrissal array are
      functionally equivalent during performance of this task. Lesions of the barrel
      cortex abolished the ability of rats to discriminate, demonstrating that this
      region is critically involved in this tactile behavior. Interestingly, sectioning
      the facial nerve, which abolished whisker movements, did not affect the ability
      to perform accurate discriminations, indicating that active whisker movements are
      not necessary for accurate performance of the task. Collectively, these results
      indicate that the trigeminal somatosensory system forms internal representations
      of external stimuli (in this case, aperture width) by integrating tactile input
      from many functionally equivalent facial whiskers and that the vibrissal array
      can function as a fine-grained distance detector without active whisker
      movements.

PMID- 11466448
TI  - Segregation and convergence of information flow through the cortico-subthalamic
      pathways.
AB  - Cortico-basal ganglia circuits are organized in parallel channels. Information
      flow from functionally distinct cortical areas remains segregated within the
      striatum and through its direct projections to basal ganglia output structures.
      Whether such a segregation is maintained in trans-subthalamic circuits is still
      questioned. The effects of electrical stimulation of prefrontal, motor, and
      auditory cortex were analyzed in the subthalamic nucleus as well as in the
      striatum of anesthetized rats. In the striatum, cells (n = 300) presenting an
      excitatory response to stimulation of these cortical areas were located in
      distinct striatal territories, and none of the cells responded to two cortical
      stimulation sites. In the subthalamic nucleus, both prefrontal and motor cortex
      stimulations induced early and late excitatory responses as a result of
      activation of the direct cortico-subthalamic pathway and of the indirect cortico
      striato-pallido-subthalamic pathway, respectively. Stimulation of the auditory
      cortex, which does not send direct projection to the subthalamic nucleus, induced
      only late excitatory responses. Among the subthalamic responding cells (n = 441),
      a few received both prefrontal and motor cortex (n = 19) or prefrontal and
      auditory cortex (n = 10) excitatory inputs, whereas a larger number of cells were
      activated from both motor and auditory cortices (n = 48). The data indicate that
      the segregation of cortical information flow originating from prefrontal, motor,
      and auditory cortices that occurred in the striatum is only partly maintained in
      the subthalamic nucleus. It can be proposed that the existence of specific
      patterns of convergence of information flow from these functionally distinct
      cortical areas in the subthalamic nucleus allows interactions between parallel
      channels.

PMID- 11466449
TI  - Different requirements for protein synthesis in acquisition and extinction of
      spatial preferences and context-evoked fear.
AB  - Many molecular accounts of long-term memory storage postulate that the synthesis
      of new proteins is necessary for long-term changes in neuronal function. These
      experiments generally have examined the learning that occurs as associations are
      acquired between neutral and biologically important stimuli. Little is known
      about the importance of protein synthesis in the establishment of memories for
      extinction, which occurs as the relations established during acquisition are
      severed. Extinction appears to be an active learning process that results in the
      formation of new memories rather than in the simple erasure or forgetting of
      memories from acquisition. Furthermore, under certain circumstances, extinction
      can result in long-term changes in behavior lasting for days to weeks. Here we
      show that although memories for the acquisition of spatial and contextual
      learning required protein synthesis, memories for extinction formed in the
      absence of protein synthesis. These results suggest that acquisition and
      extinction are mediated by distinct molecular mechanisms and that long-term
      memories can form in the absence of protein synthesis.

PMID- 11466450
TI  - Synaptic heterogeneity and stimulus-induced modulation of depression in central
      synapses.
AB  - Short-term plasticity is a pervasive feature of synapses. Synapses exhibit many
      forms of plasticity operating over a range of time scales. We develop an
      optimization method that allows rapid characterization of synapses with multiple
      time scales of facilitation and depression. Investigation of paired neurons that
      are postsynaptic to the same identified interneuron in the buccal ganglion of
      Aplysia reveals that the responses of the two neurons differ in the magnitude of
      synaptic depression. Also, for single neurons, prolonged stimulation of the
      presynaptic neuron causes stimulus-induced increases in the early phase of
      synaptic depression. These observations can be described by a model that
      incorporates two availability factors, e.g., depletable vesicle pools or
      desensitizing receptor populations, with different time courses of recovery, and
      a single facilitation component. This model accurately predicts the responses to
      novel stimuli. The source of synaptic heterogeneity is identified with variations
      in the relative sizes of the two availability factors, and the stimulus-induced
      decrement in the early synaptic response is explained by a slowing of the
      recovery rate of one of the availability factors. The synaptic heterogeneity and
      stimulus-induced modifications in synaptic depression observed here emphasize
      that synaptic efficacy depends on both the individual properties of synapses and
      their past history.

PMID- 11466452
TI  - Plasticity of Y1 and Y2 receptors and neuropeptide Y fibers in patients with
      temporal lobe epilepsy.
AB  - Marked expression of neuropeptide Y (NPY) and its Y2 receptors in hippocampal
      mossy fibers has been reported in animal models of epilepsy. Because NPY can
      suppress glutamate release by activating presynaptic Y2 receptors, these changes
      have been proposed as an endogenous protective mechanism. Therefore, we
      investigated whether similar changes in the NPY system may also take place in
      human epilepsy. We investigated Y1 and Y2 receptor binding and NPY
      immunoreactivity in hippocampal specimens that were obtained at surgery from
      patients with temporal lobe epilepsy and in autopsy controls. Significant
      increases in Y2 receptor binding (by 43-48%) were observed in the dentate hilus,
      sectors CA1 to CA3, and subiculum of specimens with, but not in those without,
      hippocampal sclerosis. On the other hand, Y1 receptor binding was significantly
      reduced (by 62%) in the dentate molecular layer of sclerotic specimens. In the
      same patients, the total lengths of NPY immunoreactive (NPY-IR) fibers was
      markedly increased (by 115-958%) in the dentate molecular layer and hilus, in the
      stratum lucidum of CA3, and throughout sectors CA1 to CA3 and the subiculum, as
      compared with autopsies. In nonsclerotic specimens, increases in lengths of NPY
      IR fibers were more moderate and statistically not significant. NPY mRNA was
      increased threefold in hilar interneurons of sclerotic and nonsclerotic
      specimens. It is suggested that abundant sprouting of NPY fibers, concomitant
      upregulation of Y2 receptors, and downregulation of Y1 receptors in the
      hippocampus of patients with Ammon's horn sclerosis may be endogenous
      anticonvulsant mechanisms.

PMID- 11466451
TI  - Effects of remote stimulation on the mean firing rate of cat retinal ganglion
      cells.
AB  - Visual stimulation outside the classical receptive field can have pronounced
      effects on cat retinal ganglion cells. We characterized the effects of such
      stimulation by varying the contrast, spatial frequency, temporal frequency, and
      spatial extent of remote drifting sinusoidal gratings. We found that the mean
      firing rate of some X-cells and most Y-cells increased to remote gratings of low
      spatial frequency and high temporal frequency and decreased to ones of high
      spatial frequency and low temporal frequency. At least 10-20% contrast was
      required to see either effect, which quickly saturated at higher contrasts. Both
      effects were substantial, raising or lowering the mean rate of some cells by over
      40 impulses/sec. Classical receptive field mechanisms were not involved because
      the remote gratings caused little or no response modulation. We conclude that, in
      addition to a mean-increasing mechanism known from previous work, a mean
      decreasing one operates in the cat retina. This mechanism prefers slower motion
      and resolves finer patterns than the mean-increasing one. We incorporate these
      findings into a model consisting of pools of small and large rectifying subunits
      of opposite polarity. Model estimates of subunit radius were primarily
      independent of eccentricity and averaged approximately 0.15 and approximately
      0.60 degrees for the mean-decreasing and mean-increasing mechanisms,
      respectively. This makes the subunits approximately the center size of central X-
      and Y-cells. Because smooth movements of the eyes, head, or body should engage
      these mechanisms under natural conditions, we propose that the mean rate changes
      that would ensue are functionally relevant to cat vision.

PMID- 11466453
TI  - Expression of protein kinase C inhibitor blocks cerebellar long-term depression
      without affecting Purkinje cell excitability in alert mice.
AB  - A longstanding but still controversial hypothesis is that long-term depression
      (LTD) of parallel fiber-Purkinje cell synapses in the cerebellum embodies part of
      the neuronal information storage required for associative motor learning.
      Transgenic mice in which LTD is blocked by Purkinje cell-specific inhibition of
      protein kinase C (PKC) (L7-PKCI mutants) do indeed show impaired adaptation of
      their vestibulo-ocular reflex, whereas the dynamics of their eye movement
      performance are unaffected. However, because L7-PKCI mutants have a persistent
      multiple climbing fiber innervation at least until 35 d of age and because the
      baseline discharge of the Purkinje cells in the L7-PKCI mutants is unknown,
      factors other than a blockage of LTD induction itself may underlie their impaired
      motor learning. We therefore investigated the spontaneous discharge of Purkinje
      cells in alert adult L7-PKCI mice as well as their multiple climbing fiber
      innervation beyond the age of 3 months. We found that the simple spike and
      complex spike-firing properties (such as mean firing rate, interspike interval,
      and spike count variability), oscillations, and climbing fiber pause in the L7
      PKCI mutants were indistinguishable from those in their wild-type littermates. In
      addition, we found that multiple climbing fiber innervation does not occur in
      cerebellar slices obtained from 3- to 6-month-old mutants. These data indicate
      (1) that neither PKC inhibition nor the subsequent blockage of LTD induction
      disturbs the spontaneous discharge of Purkinje cells in alert mice, (2) that
      Purkinje cell-specific inhibition of PKC detains rather than prevents the
      developmental conversion from multiple to mono-innervation of Purkinje cells by
      climbing fibers, and (3) that as a consequence the impaired motor learning as
      observed in older adult L7-PKCI mutants cannot be attributable either to a
      disturbance in the baseline simple spike and complex spike activities of their
      Purkinje cells or to a persistent multiple climbing fiber innervation. We
      conclude that cerebellar LTD is probably one of the major mechanisms underlying
      motor learning, but that deficits in LTD induction and motor learning as observed
      in the L7-PKCI mutants may only be reflected in differences of the Purkinje cell
      signals during and/or directly after training.

PMID- 11466454
TI  - Beta and gamma frequency synchronization by dendritic gabaergic synapses and gap
      junctions in a network of cortical interneurons.
AB  - Distinct interneuron populations innervate perisomatic and dendritic regions of
      cortical cells. Perisomatically terminating GABAergic inputs are effective in
      timing postsynaptic action potentials, and basket cells synchronize each other
      via gap junctions combined with neighboring GABAergic synapses. The function of
      dendritic GABAergic synapses in cortical rhythmicity, and their interaction with
      electrical synapses is not understood. Using multiple whole-cell recordings in
      layers 2-3 of rat somatosensory cortex combined with light and electron
      microscopic determination of sites of interaction, we studied the interactions
      between regular spiking nonpyramidal cells (RSNPCs). Random samples of unlabeled
      postsynaptic targets showed that RSNPCs placed GABAergic synapses onto dendritic
      spines (53 +/- 12%) and shafts (45 +/- 10%) and occasionally somata (2 +/- 4%).
      GABAergic interactions between RSNPCs were mediated by 4 +/- 2 axodendritic
      synapses and phased postsynaptic activity at beta frequency but were ineffective
      in phasing at gamma rhythm. Electrical interactions of RSNPCs were transmitted
      via two to eight gap junctions between dendritic shafts and/or spines. Elicited
      at beta and gamma frequencies, gap junctional potentials timed postsynaptic
      spikes with a phase lag, however strong electrical coupling could synchronize
      presynaptic and postsynaptic activity. Combined unitary GABAergic and gap
      junctional connections of moderate strength produced beta and gamma frequency
      synchronization of the coupled RSNPCs. Our results provide evidence that
      dendritic GABAergic and/or gap junctional mechanisms effectively transmit
      suprathreshold information in a population of interneurons at behaviorally
      relevant frequencies. A coherent network of GABAergic cells targeting the
      dendrites could provide a pathway for rhythmic activity spatially segregated from
      perisomatic mechanisms of synchronization.

PMID- 11466455
TI  - Nares occlusion eliminates heterosexual partner selection without disrupting
      coitus in ferrets of both sexes.
AB  - Using an airtight Y maze and a new method to induce peripheral anosmia in
      ferrets, we assessed the contribution of conspecific odors, either alone or in
      combination with visual and auditory signals, to heterosexual partner preference.
      Sexually naive ferrets were gonadectomized and treated with sex steroids, after
      which their nares were either bilaterally occluded using dental impression
      material or were sham-occluded. Behavioral and histological evidence suggested
      that nares occlusion blocked access of odors to the main olfactory epithelium for
      the duration of the study. Sham-occluded females and males preferred to approach
      odor only or odor plus visual plus auditory cues from opposite-sex conspecifics,
      whereas nares-occluded ferrets approached opposite- and same-sex cues equally.
      All ferrets subsequently mated successfully in tests conducted in a small
      chamber. When retested in the Y maze, sham-occluded females and males again
      preferred to approach odor-only or odor plus visual plus auditory cues from
      opposite-sex ferrets, whereas nares-occluded subjects showed no such preference
      even in tests when a brief physical interaction with tethered stimulus ferrets
      was allowed after each trial. Our results show that in the ferret, a carnivore,
      the detection and processing of volatile odors from conspecifics by the main
      olfactory system is required for heterosexual mate choice.

PMID- 11466456
TI  - Blockade of D1 dopamine receptors in the ventral tegmental area decreases cocaine
      reward: possible role for dendritically released dopamine.
AB  - This study was designed to assess the involvement of D1 dopamine actions in the
      ventral tegmental area (VTA) on intravenous cocaine self-administration. Rats
      were trained to self-administer intravenous injections of cocaine (1.0 mg/kg per
      injection) on a fixed-ratio 1 (FR-1) schedule or a progressive ratio (PR)
      schedule of reinforcement and then were tested under the influence of bilateral
      VTA injections of the D1 dopamine receptor antagonist SCH 23390 or the 5-HT2
      receptor antagonist ketanserin. SCH 23390 increased cocaine self-administration
      on the FR-1 schedule but decreased it on the PR schedule. Injections of
      ketanserin were ineffective, as were injections of SCH 23390 in a site 1 mm
      dorsal or 1 mm rostral to the effective VTA site. These data suggest a role for
      dendritically released dopamine, presumably acting through D1 receptors located
      on the axons of GABAergic or glutamatergic inputs to the VTA, in the
      effectiveness of cocaine reward.

PMID- 11466457
TI  - Lesser proximal interphalangeal joint arthrodesis: a retrospective analysis of
      the peg-in-hole and end-to-end procedures.
AB  - A retrospective study was performed to compare the prevalence of complications in
      peg-in-hole and end-to-end arthrodesis procedures. The authors reviewed 177
      second, third, and fourth proximal interphalangeal joint fusions for the
      correction of hammer toe deformities in 85 patients from 1988 to 1998 at the
      Temple University School of Podiatric Medicine. The average age of the patients
      was 49 years. Sixteen percent (14) of the subjects were male and 84% were (71)
      female. Upon follow-up, the fourth digit was generally associated with a greater
      number of complications for the end-to-end and peg-in-hole procedures, with the
      second digit being the most common site of fusion. The prevalence of
      complications was evaluated using contingency table analysis and expressed as a
      percent of total complications (27%, the end-to-end group; 17%, the peg-in-hole
      group). A subset of complications deemed clinically relevant was also computed.
      Similarly, the prevalence of clinically relevant complications for the end-to-end
      (10%) and the peg-in-hole (9%) procedures was not statistically significant.
      Therefore, this study showed no statistically significant differences in the
      total or clinically relevant complications between end-to-end and the peg-in-hole
      arthrodesis procedures.

PMID- 11466458
TI  - Symmetry of plantar pressures and vertical forces in healthy subjects during
      walking.
AB  - The purpose of this study was to determine the degree of symmetry for in-shoe
      plantar pressure and vertical force patterns between the left and right feet of
      healthy subjects during walking. Thirty subjects with a mean age of 29.6 years
      participated in the study. Each subject walked a distance of 8 m three times
      while in-shoe plantar pressure and vertical force data were collected. A total of
      12 steps were analyzed for both feet, and maximum vertical force, peak pressure,
      and pressure-time integrals were calculated for four plantar regions of the foot.
      No differences in the three variables were noted between male and female
      subjects. Plantar pressure and vertical force patterns were found to be
      symmetrical between the left and right feet, except for two of the four plantar
      regions studied. Only the forefoot and rearfoot regions were found to show
      significant differences between the left and right feet for plantar pressure and
      vertical force, respectively. The degree of asymmetry for these two plantar
      regions in the same foot, however, was minimal.

PMID- 11466459
TI  - A prospective study of predictors for foot ulceration in type 2 diabetes.
AB  - One hundred eighty-seven type 2 diabetic patients without a history of foot
      ulceration were followed for a mean period of 3.6 years to investigate the
      incidence of foot ulceration in a diabetes cohort and to analyze risk factors for
      foot ulceration by multivariate means. During the study, 10 subjects developed 18
      forefoot ulcerations. In multivariate logistic regression, significant predictors
      for foot ulceration were an elevated vibration perception threshold (VPT)
      (relative risk [RR] = 25.4), an increased plantar pressure (RR = 6.3), and daily
      alcohol intake (RR = 5.1). This is the first prospective study to demonstrate
      plantar pressure and daily alcohol intake as predictors of foot ulceration among
      patients without previous ulceration. Further, VPT could be confirmed as the
      strongest predictor for foot ulceration, and it was clearly demonstrated that the
      more pronounced severity of complications occurred among subjects with elevated
      VPT.

PMID- 11466460
TI  - Onychomycosis: an analysis of 50 cases and a comparison of diagnostic techniques.
AB  - Onychomycosis is an extremely common condition that is increasing in prevalence.
      Although often innocuous, it may be complicated by discomfort and secondary
      bacterial infections. Recently introduced oral medications may be highly
      effective in the eradication of this condition; however, they may carry with them
      significant expense and potentially serious side effects. Prior to the initiation
      of antifungal oral therapy, definitive diagnosis is mandatory. This study
      compares the sensitivity of potassium hydroxide (KOH) preparations, surgical
      pathology diagnostic testing (SPDT), and culture techniques for the detection of
      onychomycosis in 50 cases of clinically suspected onychomycosis. Analysis showed
      that SPDT was significantly more sensitive when compared to KOH and culture. The
      results suggest that SPDT may be the true gold standard for the diagnosis of
      onychomycosis.

PMID- 11466461
TI  - Podiatric medical applications of posterior night stretch splinting.
AB  - Podiatric physicians encounter many conditions, especially in sports medicine,
      that involve pain in the vicinity of the rearfoot or lower leg. These conditions
      are often associated with ankle equinus and may affect either child or adult
      sports participants. A review of the literature and clinical experience identify
      posterior night stretch splinting as an effective adjunct in the treatment of
      persistent symptomatic plantar fasciitis, negating the need for corticosteroid
      injections, further protracted pain, or surgery. This article reviews clinical
      cases in which night stretch splinting was used for a variety of diagnoses.
      Further research is needed into its efficacy for conditions other than plantar
      fasciitis.

PMID- 11466462
TI  - Syndrome of painful legs and moving toes: a case study.
AB  - Painful legs and moving toes syndrome is characterized by spontaneous causalgic
      pain in the lower extremities associated with peculiar involuntary movements of
      the lower extremities, especially the toes and feet. The pain is diffuse,
      intractable, aching, and deep. The movements consist of persistent writhing
      movements in the digits that cannot be limited voluntarily. The syndrome has been
      observed after a variety of abnormalities affecting the posterior nerve roots,
      the spinal ganglia, and the peripheral nerves. This article reviews commonly
      reported findings and current concepts in the etiology and management of this
      condition.

PMID- 11466463
TI  - Acute Charcot foot changes versus osteomyelitis: does Tc-99m HMPAO labeled
      leukocytes scan differentiate?
AB  - Osteomyelitis often complicates a diabetic neuropathic foot, leading to
      amputation, decreased function, and quality of life. Therefore, early detection
      and treatment are paramount. Furthermore, neuroarthropathic (Charcot) changes in
      the foot often resemble infection and must be differentiated. Currently, the Tc
      99m HMPAO Labeled Leukocytes Scan is considered to be the most reliable
      noninvasive imaging modality of choice in determining Charcot foot changes versus
      osteomyelitis. The purpose of this article is to alert the clinician that
      although the Tc-99m HMPAO Labeled Leukocytes Scan may be the second most reliable
      test next to bone biopsy for determining osteomyelitis, false positives do occur.

PMID- 11466464
TI  - Partial calcanectomy in the treatment of chronic heel ulceration.
AB  - Chronic decubitus ulceration of the heels is a common condition encountered by
      podiatric physicians, especially in diabetic patients. Very often these
      ulcerations can progress to osteomyelitis of the calcaneus. Many times, this in
      turn leads to a below-the-knee amputation. A partial calcanectomy is a viable
      alternative to below-the-knee amputation. A more functional limb both
      mechanically and cosmetically is achieved, and the morbidity and mortality
      associated with the calcanectomy is less than with a below-the-knee amputation. A
      brief overview of the history and outcomes associated with this procedure is
      outlined and a case utilizing a partial calcanectomy is presented.

PMID- 11466465
TI  - Brachymetatarsia of the third and fourth metatarsals.
AB  - A cylindrical autogenous diaphyseal bone graft from the neighboring second and
      fifth metatarsals to correct brachymetatarsia of the third and fourth metatarsals
      was last described by Biggs in 1979. The authors present a literature review and
      case report for the treatment of the rare clinical entity of brachymetatarsia.

PMID- 11466466
TI  - Isolated gouty tophus of a tibial sesamoid of the foot.
AB  - A case of tophaceous gout involving a foot sesamoid is described in a middle-aged
      man with a history of chronic gout. Microscopic findings consisting of tophaceous
      foci located beneath an intact hyaline articulating surface are correlated with
      associated radiographs.

PMID- 11466467
TI  - Bilateral forefoot gangrene secondary to Lemierre's disease.

PMID- 11466469
TI  - Axonal protein synthesis and transport.
AB  - Recent evidence has challenged our ideas about the nature of axonal protein
      synthesis and transport. Previous metabolic labeling evidence supported the idea
      that all axonal proteins were synthesized in the cell body and then transported
      as formed cytoplasmic structures into the axon. Recent evidence suggests that
      neither the synthesis nor the transport of axonal proteins is that simple. Though
      most axonal proteins do appear to be synthesized in the neuronal cell body, a
      small amount of protein appears to be synthesized intra-axonally in some axons.
      Though small in amount, intra-axonal protein synthesis may be important
      functionally in some axons. Recent experiments have also begun to identify the
      presence of a rich array of transport motors in axons, including many members of
      the kinesin, dynein and myosin families. Progress is being made in identifying
      which cargoes are being transported by which of these motors. Finally, recent
      experiments have addressed an old question about whether axoplasmic proteins are
      transported as filamentous polymers or as soluble components in axons. The answer
      is that both mechanism can be used in axons. For example, neurofilament protein
      can move in its particulate or polymeric state, while tubulin can move in its
      soluble or unpolymerized state.

PMID- 11466470
TI  - Axonal mRNAs: functional significance in vertebrates and invertebrates.
AB  - Sorting of defined mRNA species to distinct cytoplasmic regions is observed
      throughout the animal kingdom in many cell types, including neurons. During the
      past years, mRNA localization to dendrites of nerve cells has been characterized
      in detail. The functional role of these transcripts appears to be obvious: Since
      dendrites are equipped with the basic translational machinery, certain proteins
      are likely to be synthesized on-site. Targeting of mRNAs to the axon of
      vertebrate neurons is less well understood. Even though some vertebrate nerve
      cells such as goldfish Mauthner neurons seem to have ribosomes within the axonal
      compartment, evidence for ongoing local translation is still preliminary. In most
      differentiated mammalian neurons the axon is thought to lack mRNAs and a protein
      synthesizing machinery. Although a few nerve cell types harbour substantial
      amounts of distinct mRNA species within the axonal domain, their functional
      significance has remained elusive until today. Recent evidence suggests that mRNA
      transport to neurites including the future axon and local translation might play
      a role in nerve cell maturation. mRNA targeting to the axon of young neurons is
      strictly correlated with differentiation. It is no longer observed in fully
      matured neurons. Finally, for many years invertebrate neurons have served as
      model systems to investigate axonal mRNA transport and its physiological
      relevance. There is no doubt that protein synthesis does take place in the axonal
      domain. However, it has to be considered that invertebrate neurons develop only
      one type of neurite, referred to as the axon. These axons are different when
      compared with those of vertebrate nerve cells since they combine characteristics
      of dendrites and axons. In fact, current evidence supports the view that the
      axonal mRNAs in invertebrate nerve cells have functions comparable to those of
      transcripts residing in the dendrites of vertebrate neurons.

PMID- 11466471
TI  - Protein synthesis in axons and its possible functions.
AB  - Proteins synthesized in neuronal cell bodies are transported along axons by fast
      and slow axonal transport. Cytoskeletal proteins and cytosolic proteins that
      travel by slow axonal transport could take years to reach the terminals of meter
      long axons, and it is difficult to see how proteins could last long enough to
      make this journey. How then are proteins supplied to the distal regions of long
      axons? Evidence has accumulated indicating that axons contain specific mRNAs and
      ribosomes and can synthesize cytoskeletal proteins and some other proteins. This
      review considers the direct evidence that proteins can be synthesized in axons
      and considers the possible functional significance of axonal protein synthesis.
      It remains unclear whether local protein synthesis could supply the cytoskeletal
      proteins and other slow-transported proteins required for the maintenance,
      plasticity, and regeneration of long axons.

PMID- 11466472
TI  - One axon, many kinesins: What's the logic?
AB  - A large number of membrane-bounded organelles, protein complexes, and mRNAs are
      transported along microtubules to different locations within the neuronal axon.
      Axonal transport in the anterograde direction is carried out by members of a
      superfamily of specialized motor proteins, the kinesins. All kinesins contain a
      conserved motor domain that hydrolyses ATP to generate movement along
      microtubules. Regions outside the motor domain are responsible for cargo binding
      and regulation of motor activity. Present in a soluble, inactive form in the
      cytoplasm, kinesins are activated upon cargo binding. Selective targeting of
      different types of kinesin motors to specific cargoes is directed by amino acid
      sequences situated in their variable tails. Cargo proteins with specific function
      at their destination, bind directly to specific kinesins for transport. Whereas
      most kinesins move to microtubule plus-ends, a small number of them move to
      microtubule minus-ends, and may participate in retrograde axonal transport.
      Axonal transport by kinesins has a logic: Fully assembled, multisubunit,
      functional complexes (e.g., ion channel complexes, signaling complexes, RNA
      protein complexes) are transported to their destination by kinesin motors that
      interact transiently (i.e., during transport only) with one of the complexes'
      subunits.

PMID- 11466473
TI  - Cytoplasmic dynein subunit heterogeneity: implications for axonal transport.
AB  - The formation and maintenance of neuronal synapses is dependent on the active
      transport of material between the cell body and the axon terminal. Cytoplasmic
      dynein is one motor for microtubule-based axonal transport. Two pools of
      cytoplasmic dynein have been identified in the axon. They are distinguished by
      their intermediate and light intermediate chain subunits. Each pool is
      transported at different rates down the axon in association with different
      proteins or organelles. This review presents several models to discuss the
      potential functional roles of these different pools of cytoplasmic dynein during
      axonal transport.

PMID- 11466474
TI  - Axonal myosins.
AB  - The myosin super family is an extended family of actin-based motor proteins that
      can be divided into 15-18 structurally distinct classes (Sellers, J. R (2000)
      Biochemica et Biophysica Acta, 1496, 3-22; Hodge, T. & Cope, M. J. T. V. (2000)
      Journal of Cell Science, 113, 3353-3354; Berg, J. S., Powell, B. C. & Cheney, R.
      E. (2001) Molecular Biology of the Cell, 12, 780-794). Many myosin classes
      contain multiple members, including different isoforms within the same species as
      well as homologous proteins from different species. A number of the myosin
      classes are expressed in multiple cell types in vertebrates, including neurons.
      Surprisingly little is known about the neuronal function of these different
      myosins. In this review we concentrate on the vertebrate myosins known to be
      present in neuronal axons. We take a simplistic view of this topic, addressing a
      number of specific questions. (1) Which myosins are present in neurons? (2) Do
      their levels change during development? (3) Are the neuronal forms unique in any
      way? (4) Which neuronal myosins are located in axons and how are they
      distributed? (5) What do these myosins do and are they essential for a specific
      neuronal function?

PMID- 11466475
TI  - Neurofilament protein synthesis and phosphorylation.
AB  - Neurofilament proteins, a major intermediate filament component of the neuronal
      cytoskeleton, are organized as 10 nm thick filaments in axons and dendrites. They
      are large, abundantly phosphorylated proteins with numerous phosphate acceptor
      sites, up to 100 in some cases, organized as numerous repeat motifs. Together
      with other cytoskeletal components such as microtubules, MAPs, actin and plectin
      like linking molecules, they make up a dynamic lattice that sustains neuronal
      function from neuronal "birthday" to apoptotic cell death. The activity of the
      neuronal cytoskeleton is regulated by phosphorylation, dephosphorylation
      reactions mediated by numerous associated kinases, phosphatases and their
      regulators. Factors regulating multisite phosphorylation of NFs are
      topographically localized, with maximum phosphorylation of NF proteins consigned
      to axons. Phosphorylation defines the nature of NF interactions with one another
      and with other cytoskeletal components such as microtubules, MAPs and actin. To
      understand how these functional interactions are regulated by phosphorylation we
      attempt to identify the relevant kinases and phosphatases, their specific targets
      and the factors modulating their activity. As an initial working model we propose
      that NF phosphorylation is regulated topographically in neurons by compartment
      specific macromolecular complexes of substrates, kinases and phosphatases. This
      implies that axonal complexes differ structurally and functionally from those in
      cell bodies and dendrites. Such protein assemblies, by virtue of conformational
      changes within proteins, facilitate ordered, sequential multisite
      phosphorylations that modulate dynamic cytoskeletal interactions.

PMID- 11466476
TI  - Microtubule motors, phosphorylation and axonal transport of neurofilaments.
AB  - The recent demonstration that the axonal transport motors kinesin and dynein
      participate in axonal transport of neurofilaments (NFs), and that the association
      of NFs with these motors is regulated by phosphorylation provides new insight
      into several aspects of axonal transport and NF biology. This review juxtaposes
      older and more recent findings on NF dynamics, and speculates on the organization
      of axonal NFs as suggested by real-time analyses of NF transport.

PMID- 11466477
TI  - Axonal transport of tubulin and actin.
AB  - Axonal transport is responsible for supplying the axonal processes with proteins
      that are synthesized in the cell body. Among the proteins that are moved by this
      mechanism are tubulin and actin, two major components of the cytoskeleton.
      Observation of the movement of metabolically labeled tubulin and actin in-vivo
      has demonstrated that tubulin and actin transport are reduced in various diseases
      and with age, but transport is increased during axonal growth and regeneration.
      These metabolic studies have also raised questions about the underlying
      mechanisms of slow axonal transport such as: what is the polymerization state of
      tubulin and actin during transport, what motors and tracks are responsible for
      their movement down the axon, and how are the transport motors coupled to tubulin
      and actin during transport? Since experiments using metabolically labeled tubulin
      and actin have not effectively addressed these questions, a variety of new in
      vitro fluorescent microscopy techniques have been devised to investigate these
      questions. These fluorescent microscopy experiments have suggested that tubulin
      can be transported in the unpolymerized soluble state and that such transport of
      soluble tubulin relies on the presence of formed microtubule tracks. It is not
      yet known what motor or motors are responsible for tubulin or actin transport in
      axons or how such a motor(s) might be coupled to such an abundant soluble cargo.

PMID- 11466478
TI  - Contribution to the knowledge of species of the genus Stephanostomum Looss, 1899
      (Digenea: Acanthocolpidae) from teleosts of the Western Mediterranean, with the
      description of S. gaidropsari n. sp.
AB  - Four species of the acanthocolpid genus Stephanostomum are redescribed from the
      digestive tract of teleosts in the Western Mediterranean: the type-species, S.
      cesticillum from Lophius piscatorius is described with a ventrally interrupted
      ring of 35 circum-oral spines and as lacking a uroproct; S. bicoronatum from
      Sciaena umbra has a ventrally interrupted ring of 31 circum-oral spines and a
      uroproct; S. pristis from Phycis phycis has an uninterrupted ring of 36 oral
      spines and no uroproct; S. minutum from Uranoscopus scaber has an uninterrupted
      ring of 36 oral spines and a uroproct. A new species, S. gaidropsari from
      Gaidropsarus mediterraneus, is described with an uninterrupted ring of 36 oral
      spines and an apparent uroproct. It differs from all other Stephanostomum species
      with similar oral spine numbers in the armament of the ejaculatory duct, and from
      various of these species by vitelline distribution, length of the genital atrium,
      oesophageal length and sucker-ratio.

PMID- 11466479
TI  - Ultrastructural description of the spore maturation stages of the clam parasite
      Minchinia tapetis (Vilela, 1951) (Haplosporida: Haplosporidiidae).
AB  - The fine structure of maturing spores of a haplosporidian parasite found in the
      gill, mantle and foot tissues of Ruditapes decussatus L. (Mollusca, Bivalvia), a
      species of commercial importance in Portugal, is described. When observed free in
      suspension, immature spores exhibit one or two epispore cytoplasmic extensions
      (ECE) which constitute a projection of a portion of the exosporoplasm, sometimes
      without ultrastructural organisation, surrounded by the plasmalemma. Free spores
      observed by light microscopy (LM) after 3-5 days of incubation in filtered sea
      water exhibit no ECE attached to the spore wall. The mature spore is ovoid to
      ellipsoid, operculate, uninucleate and measures c. 4.8 microm long and c. 3.9
      microm wide. The spore shape and size and the identity of the host living in the
      same geographical region suggest that this species is the same as previously
      described using LM observations as Haplosporidium tapetis Vilela, 1951 and later
      transferred to Minchinia Labbe, 1896.

PMID- 11466480
TI  - Redescriptions of two echinostomes from freshwater fishes, with comments on
      Singhia Yamaguti, 1958 and Caballerotrema Prudhoe, 1960 (Digenea:
      Echinostomatidae).
AB  - The type-species of Singhia and Caballerotrema (Digenea: Echinostomatidae),
      parasites of freshwater fishes which have previously been assigned to the
      subfamily Singhiinae Yamaguti, 1958, are redescribed. One of the specimens of the
      type-series of Caballerotrema brasiliense Prudhoe, 1960 was identified as C.
      aruanense Thatcher, 1980. C. arapaimense Thatcher, 1980 is considered a species
      inquirenda. Himasthla piscicola Stunkard, 1960 is transferred to Caballerotrema
      as C. piscicola n. comb. The generic diagnoses of Singhia and Caballerotrema are
      redefined and Singhia is re-allocated to the Echinostomatinae Looss, 1899, the
      Singhiinae becoming a synonym of the latter.

PMID- 11466481
TI  - Amphicreadium n. g. (Digenea: Lepocreadiidae) from monacanthid fishes
      (Tetraodontiformes) from the coast of northern Tasmania.
AB  - A new lepocreadiid genus, Amphicreadium, is erected for the species A.
      denspeniculus n. sp. from Acanthaluteres vittiger and for an unnamed species from
      Meuschenia freycineti, both from off northern Tasmania. The new genus is
      distinguished from all other members of its family by its amphistomatous body
      plan.

PMID- 11466482
TI  - Description of the life-cycle stages of Brachylaima cribbi n. sp. (Digenea:
      Brachylaimidae) derived from eggs recovered from human faeces in Australia.
AB  - The life-cycle of Brachylaima cribbi n. sp. was established in the laboratory.
      Asymmetrical brachylaimid eggs, measuring 26-32 microm (29.1 microm) long and 16 
      17.5 microm (16.6 microm) wide, were recovered from human faeces and fed to the
      helicid land snail Theba pisana as the first intermediate host. Sporocysts and
      cercariae were recovered from the T. pisana eight weeks after infection. The
      cercariae were used to infect the helicid land snails Cernuella virgata and Helix
      aspersa as second intermediate hosts. Metacercariae were recovered from the
      kidneys of these snails and used to infect mice. Adults of Brachylaima cribbi n.
      sp. were recovered from the small intestine of the mice. The differential
      features of B. cribbi n. sp. are the specificity for helicid snails as first and
      second intermediate hosts; characteristic ventral sucker and body cercarial
      chaetotaxy; and a long slender adult worm with equal size suckers in the first
      quarter of the worm, the ventral sucker occupying 41% of the body width, the
      uterus extending anterior to the ventral sucker and the vitelline follicles
      falling short of the posterior margin of the ventral sucker. No other known
      Brachylaima species exhibits all of these features. B. cribbi n. sp. is the first
      brachylaimid known to have infected humans and is probably of European origin, as
      the intermediate host snails were all introduced into Australia from Europe.

PMID- 11466483
TI  - Sundapolystoma chalconotae n. g., n. sp. (Monogenea: Polystomatidae) from Rana
      chalconota (Schlegel) of Peninsular Malaysia.
AB  - Sundapolystoma chalconotae. n. g., n. sp. (Polystomatidae, Polystomatinae) is
      proposed for a new polystomatid from the urinary bladder of Rana chalconota
      (Schlegel) in Peninsular Malaysia. This is the first species of polystomatid to
      be described from the amphibians of Peninsular Malaysia and the second for the
      Southeast Asian region. This new genus, as exemplified by S. chalconotae, differs
      from other polystomatids, and in particular Parapolystoma Ozaki, 1935 (P.
      bulliense (Johnston, 1912) Ozaki, 1935 and P. johnstoni Pichelin, 1995), in
      having a tubular uterus and a single diffuse testis. P. crooki Vande Vusse, 1976
      is similar to S. chalconotae in having a similar type of uterus and testis, and
      is re-assigned as Sundapolystoma crooki (Vande Vusse, 1976) n. comb. S.
      chalconotae differs from S. crooki in having anchors with a longer outer root
      rather than a longer inner root and 7-8 genital spines compared to 9-13 in S.
      crooki.

PMID- 11466485
TI  - A guest editorial: is "male ob/gyn" a new oxymoron?

PMID- 11466487
TI  - Androgens in postmenopausal women: production, possible role, and replacement
      options.
AB  - The physiology of normal androgen production in women has not been well
      understood. Aging, per se, accounts for much of the reduction in both ovarian and
      adrenal androgen production; and natural menopause does not result in an abrupt
      decline in testosterone production. Therefore, the definition of an androgen
      deficiency state in women, in the absence of adrenal suppression and/or bilateral
      oophorectomy, has been difficult. Nevertheless there are well-documented
      beneficial effects of androgen on many organ systems, including bone and the
      brain. This review focuses on the physiology of androgens in postmenopausal women
      and includes a discussion of the definition of an androgen deficiency state, the
      anticipated effects of androgen on several parameters of health, and possible
      ways in which androgens may be administered to women.

PMID- 11466488
TI  - The value of tan lines: vulvar melanoma and ultraviolet rays.
AB  - Recreational sun exposure of the general population has increased. There is less
      clothing on the beaches, increased accessibility to tropical beaches, and
      increased use of artificial suntanning equipment. The vulva, traditionally, has
      been protected from sun exposure. In this age of nude sunbathing, particularly
      within the confines of a tanning bed, it is interesting to ponder whether such
      exposure would affect the incidence of melanoma of the vulva.

PMID- 11466489
TI  - Influence of nonradical hysterectomy on the function of the lower urinary tract.
AB  - Hysterectomy will sometimes be identified by the patient as the starting point of
      lower urinary tract (LUT) symptoms. However, it is questionable whether there is
      a causal relationship. A number of epidemiological studies have found an increase
      in the relative risk of LUT symptoms of up to 2.2 in patients after simple
      hysterectomy. However, in numerous prospective, controlled studies including
      studies using urodynamic testing before and after the operation, such an effect
      can not be established. The discrepancy between the two types of studies is
      striking. A number of possible explanations are presented. It is concluded that
      there is little or no effect of nonradical hysterectomy on the lower urinary
      tract function.

PMID- 11466490
TI  - [Comparison of MRA and angiography in the follow-up of intracranial aneurysms
      treated with GDC].
AB  - OBJECTIVE: Evaluation of TOF 3D MRA compared to angiography in the follow-up of
      intracranial aneurysms treated by Guglielmi detachable coils (GDC). MATERIAL: and
      method: Prospective analysis of follow-up MRA and angiographies for 20 patients
      with 22 aneurysms. There were 2 MRAs for 3 aneurysms giving a total of 25 cases.
      RESULTS: A poor correlation between MRA and angiography was observed in 21 cases
      of 25. For 9 cases, stable exclusion (95-100%) visible on MRA was confirmed by
      angiography. For 12 other cases, a residual flow within the aneurysmal neck or a
      residual flow between coils was detected by MRA and confirmed by angiography. A
      poor correlation was found in 4 cases out of 25: 3 residual flows within the
      aneurysmal neck and 1 residual flow within the coil mass not visible on MRA. MRA
      has a sensibility of 75% for the detection of an anomaly, a specificity of 100%,
      a positive predictive value of 100% and a negative predictive value of 69.2%. MRA
      is able to detect a large residual flow within aneurysmal neck and a re-growth,
      which would need a second embolization. Anomalies not visible on MRA as observed
      in our study, residual flow within the coil mass and the aneurysmal neck, do not
      require complementary treatment. CONCLUSION: A normal TOF 3D MRA can avoid an
      angiography in the follow-up of an intracranial aneurysm treated by GDC.

PMID- 11466491
TI  - [Moyamoya disease: importance of the MRI-MRA combination and difficulties in
      management and follow-up in 7 cases].
AB  - PURPOSE: To point out the importance of both MRI and MR angiography for the
      diagnosis and follow-up of moyamoya disease. MATERIALS AND METHODS: We report
      seven cases. MRI was performed in the initial phase in three cases. MR
      angiography without conventional angiography led to the diagnosis in one case.
      Conventional angiography was performed in six cases. Follow-up MRI and MR
      angiography were obtained in two. RESULTS: The initial MRI revealed ischemic
      lesions in the sylvian territory in two cases, and a cerebral malformation in
      one, after-effect lesions in two, and cerebral atrophy and ventricular dilatation
      in one. Conventional angiography provided the diagnosis of moyamoya disease in
      all cases, associated with cerebral arteriovenous malformation in two.
      CONCLUSION: MRI and MRA should be performed for the diagnosis and follow-up of
      moyamoya disease.

PMID- 11466492
TI  - Frequency of cavum veli interpositi in non-psychotic population: a magnetic
      resonance imaging study.
AB  - This prospective MRI investigation was performed to determine the incidences of
      the cavum veli interpositi (CVI) in 505 (242 Male, 263 Female) non-psychotic
      persons. The mean age of the population was 39,179 +/- 0,904 (40,461 +/- 1,395
      Male, 38 +/- 1,166 Female). There was no significant difference between the means
      of age in male and female groups (t-test, DF=479, p>0,05). The incidences of the
      CVI were 5.77%, 1.89%, 5.66%, 8.24%, 5%, 4.55%, 7.94%, 3.03% for age group of 0
      9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79 respectively. There was no
      significant difference between the incidences of the CVI in age-groups
      (chi(2)=3.804, DF=7, p>0.05). The incidences of the CVI were 5.54%, 6.61%, 4.56%
      for whole, male, and female populations respectively. There was no significant
      difference between the incidences of the CVI in both sexes (chi(2)=1.01, DF=1,
      p>0.05).

PMID- 11466493
TI  - [MRI screening of vestibular schwannomas without gadolinium: usefulness of the
      turbo gradient spin echo T2-weighted pulse sequence].
AB  - The purpose of this retrospective MRI work was to evaluate the use of turbo
      gradient spin echo (TGSE) high resolution imaging for the detection of eighth
      nerve schwannomas, without injection of gadolinium. The TGSE sequence (slice
      thickness: 3 mm with 1.5 mm interleaving; matrix: 512) was compared with a
      reference sequence: T1-weighted spin echo (SE) after gadolinium injection (slice
      thickness: 3 mm, matrix: 256). Among 380 internal auditory meatus (IAM) explored,
      34 abnormalities were detected on T2-weighted TGSE images compared with 19 on
      contrast-enhanced T1-weighted SE images. This new sequence has a 100%
      sensitivity, a 96% specificity and a 100% negative predictive value. Using a
      rigorous protocol for IAM analysis with the TGSE sequence, gadolinium injection
      may no longer be needed systematically for vestibular schwannoma screening, but
      might only be necessary when an abnormality or a doubt persists after TGSE. This
      approach allows about 20% cost reduction for each patient, a savings of 11,433
      euros considering only the true negatives observed in this study.

PMID- 11466494
TI  - [How to assess cerebrospinal fluid flow rate].
AB  - The kinetics of cerebrospinal fluid can be analyzed equally well with velocity
      imaging and 3D T2-weighted flow sensitive sequences. These techniques constitute
      a valuable evaluation for intracranial and spinal CSF obstructive pathology.

PMID- 11466495
TI  - [What is your diagnosis? Lhermitte-duclos disease].

PMID- 11466496
TI  - Discrepancy between diffusion and perfusion imaging in a patient with transient
      ischaemic attack.
AB  - We report paradoxical and ambiguous imaging findings in a patient with transient
      ischaemic attack (TIA). Perfusion-weighted (PW) MRI obtained 2 hours after
      symptoms onset showed a hypoperfused area in a region compatible with the focal
      deficit, while diffusion-weighted (DW) MRI was considered negative. Despite the
      complete resolution of the symptoms which had already begun at the end of the
      first MR examination, follow up DW MRI at 3 days showed partial conversion to
      hyperintensity of the initially hypoperfused area. This case illustrates that PW
      and DW MRI have to be used in combination and at different time points to
      correctly diagnose and manage ischaemic stroke because PW MRI is more sensitive
      than DW MRI for very early detection of ischaemia and delayed DW MRI provides the
      final signature of brain damage even in case of complete clinical recovering.

PMID- 11466497
TI  - Bilateral anomalous origins of the posterior meningeal artery from the ascending
      pharyngeal arteries.
AB  - We present a rare case of angiographically confirmed dural arteriovenous fistula
      supplied mainly by the posterior meningeal artery with bilateral anomalous
      origins from the bilateral ascending pharyngeal arteries. The bilaterality of the
      origins of the posterior meningeal artery is important in the angiographic
      diagnosis and management of a dural vascular malformation in the posterior fossa
      or the posterior part of the falx cerebri.

PMID- 11466498
TI  - Cortical dysplasia with subcutaneous angioma and dilated dural venous sinuses.
AB  - We report a rare case with dilated dural venous sinuses, cortical dysplasia, and
      a subcutaneous angioma in the forehead. These lesions may be derived from some
      factors in the certain period of gestation, during which dural venous sinuses
      dilate due to increased intracranial pool of blood.

PMID- 11466499
TI  - [Glioma in a patient with multiple sclerosis].
AB  - The simultaneous occurrence of multiple sclerosis and a primary brain neoplasm is
      exceptional: only 32 cases have been reported in the literature. We report the
      case of a 30-year-old woman with multiple sclerosis proven for 10 years who
      developed a grade II astrocytoma revealed by MRI. At the pathology examination,
      there was no cellular continuity with areas of demyelinized white matter. Unlike
      the hypothesis put forward in certain publications describing this association
      that argue for an induction link between these two entities, our case did not
      demonstrate any spatial or temporal relationship suggestive a common cause.

PMID- 11466500
TI  - [Optochiasmatic tuberculoma: complication of tuberculous meningitis. Report of a
      case and review of the literature].
AB  - Optochiasmatic tuberculomas are rare and have a poor prognosis if not diagnosed
      early and treated adequately. We report the case of 4-year-old boy who presented
      a chiasmatic tuberculoma after tuberculous meningitis revealed by progressive
      visual failure. Cerebral gadolinium enhanced magnetic resonance imaging
      demonstrated a chiasmatic and a brainstem ringlike enhancing lesions. Outcome was
      favorable with antituberculosis therapy and corticosteroids. Are recalled the
      diagnostic aspects, notably the neuroradiological findings, in this particular
      localisation of tuberculosis with a review of the similar thirty-three cases
      reported in the literature.

PMID- 11466501
TI  - Inverse correlation of TRF1 expression and cell proliferation in human primary
      intracranial tumors.
AB  - BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a
      physiological homeostatic mechanism controlling cellular proliferative potential.
      TRF1 is involved in a negative feedback mechanism that allows telomere shortening
      by inhibiting the activity of telomerase. Down-regulation of TRF1 expression
      results in telomere elongation and may be involved in cell immortalization. The
      goal of the present study was to determine whether routine immunohistochemical
      (IHC) techniques can characterize TRF1 expression in different human brain tumor
      specimens and whether it correlates with other indices of brain tumor's
      proliferative potential. METHODS: A cohort of 20 flash-frozen surgical specimens
      [14 meningiomas and 6 anaplastic astrocytomas (AA)] were evaluated for TRF1
      expression. Results of parallel investigations of tumor's proliferative indices
      as assessed by Ki67 labeling index (LI) determinations were cross-correlated with
      TRF1 expression results and histotype. RESULTS: We demonstrated variable levels
      of TRF1 expression in 12 out of 14 (87.5%) meningioma samples. By contrast, we
      detected no expression of TRF1 in tissue samples from AA (p=0.008). The Ki67 LI
      was higher in AA than in meningioma samples (15.21+/-9.34 vs 26.6+/-13.89,
      p=0.044). Statistical analysis revealed a significant inverse correlation between
      TRF1 expression, histotype, and LI (c2=14.1; p=0.0008). CONCLUSIONS: We
      demonstrated for the first time that routine IHC techniques are capable to
      identifying TRF1 expression in intracranial tumors. The results suggest that TRF1
      is heterogeneously expressed in meningiomas, and absent in AA. The TRF1 status in
      intracranial tumors might be of prognostic value and possibly represent a
      potential application for biologically targeted therapeutic strategies.

PMID- 11466502
TI  - Neuroprotective effect of recombinant human erythropoietin in experimental
      subarachnoid hemorrhage.
AB  - BACKGROUND: Acute cerebral vasoconstriction and subsequent brain ischemia, often
      occurring in the early phase of subarachnoid hemorrhage (SAH), are critical
      problems in the management of patients affected by ruptured intracranial
      aneurysms. It is known that nitric oxide (NO) decreases during SAH with
      impairment of cerebrovascular relaxation, and glutamate is mainly involved in the
      consequent brain ischemic damage. Recently, erythropoietin (EPO) has shown to
      exert a neuroprotective effect during cerebral ischemia by enhancing the NO
      system activity. In the present study the effect of systemic administration of
      recombinant human erythropoietin (rHuEPO) has been investigated in a rabbit model
      of SAH. METHODS: Thirty-two rabbits were assigned to four groups: 1) Control; 2)
      SAH; 3) SAH plus placebo; 4) SAH plus rHuEPO. Experimental SAH was induced by
      injecting autologous blood into the cisterna magna. rHuEPO, at a dose of 1000
      IU/kg, and placebo were given 5 minutes after SAH. Administration was repeated
      three times during 24 hours. The animals were killed 24 hours after SAH by a
      perfusion-fixation method. Luminal cross-sections of the basilar artery were
      measured by computer-assisted morphometric analysis. Ischemic injury was
      histologically evaluated by analysis of the frequency of ischemia-induced damaged
      cortical neurons. RESULTS: Administration of rHuEPO significantly reversed the
      vasoconstriction of the basilar artery in Group 4 compared with the other groups
      (p<0.05). Histological examination showed a significant reduction in total
      damaged neurons count in Group 4 compared with the other groups (p<0.01).
      CONCLUSIONS: These results suggest that rHuEPO is effective in attenuating acute
      cerebral vasoconstriction and ischemic brain injury following experimental SAH.

PMID- 11466503
TI  - Single-screw fixation for acute Type II odontoid fracture.
AB  - BACKGROUND: The management of odontoid fractures is still controversial. The main
      current trends of treatment are conservative management with HALO immobilization,
      posterior surgical fixation or anterior surgical fixation. The authors report a
      consecutive series of 17 cases of patients with acute Type II odontoid fracture
      treated between November 1994 and February 2000. METHODS: Since June 1997
      anterior odontoid screw fixation was performed in nine cases. The technical
      aspects of the internal fusion are described. RESULTS: Spinal stabilization was
      achieved in all patients. The postoperative neuroimaging demonstrates the
      successful positioning of the odontoid screw of all patients. CONCLUSIONS: The
      success of this treatment depends on patients' selection, attention to technical
      operative details and adequate follow-up. Internal screw fixation gives immediate
      direct fixation of the fracture, offers a high rate of fusion without requiring
      prolonged HALO immobilization, it gives a reduction of the cervical pain and
      preserves the normal mobility of C1-C2.

PMID- 11466504
TI  - Frontotemporal orbitozygomatic craniotomy to exposure the cavernous sinus and its
      surrounding regions. Microsurgical anatomy.
AB  - BACKGROUND: The microsurgical anatomy of the cavernous sinus and its surrounding
      regions were examined via frontotemporal orbitozygomatic (FTOZ) craniotomy.
      Combined with other deep osteotomies, the possibility of exposing the petroclival
      region and basilar artery was also explored. METHODS: The study was made on 20
      sides of 10 cadaveric specimens fixed with formalin, with the help of the
      surgical microscope (magnification 5-15). RESULTS: The FTOZ was performed with
      frontotemporal and orbitozygomatic flaps. Extradurally, V2, V3, the trigeminal
      ganglion, the posterior vertical segment of the intracavernous ICA and the VI
      nerve were exposed by FTOZ craniotomy. By further removal of the petrous apex
      (Kawase's triangle), exposure could be extended to the petroclival region; with
      anterior modification of the microscopic light, in 50% of the specimens, exposure
      reached as low as the convergence of the vertebral arteries. The anterior part of
      the cavernous sinus and the orbital apex were examined by removing the anterior
      clinoid process, orbital roof and unroofing the optic canal. Intradurally, the
      intrapeduncular fossa (upper 1/3 of the clivus) was examined. The intracavernous
      cranial nerves and vessels were studied via lateral and superior wall approaches.
      By removing both the anterior and posterior clinoid processes together, in 80% of
      the specimens, the exposure could be carried as far as the midpoint of the
      basilar artery. CONCLUSIONS: FTOZ craniotomy could be used to treat lesions
      involving the cavernous sinus and its surrounding regions. Incorporated with the
      petrous apectomy, it could be used to expose the petroclival region and, in
      selected cases, exposure could be extended to the convergence of the vertebral
      arteries. Combined with anterior and posterior clinoidectomies, it could also be
      used to treat midpoint regions of the basilar artery.

PMID- 11466505
TI  - Traumatic intracerebellar hemorrhagic contusions and hematomas.
AB  - BACKGROUND: Traumatic intracerebellar hemorrhagic contusions and hematomas (TIHC)
      are unusual lesions and their surgical management remains controversial. METHODS:
      From January 1990 to July, 1998, 3290 patients underwent computed tomography for
      acute head trauma at our Institution. Eighteen patients (0.54%) were
      retrospectively identified as harboring TIHC. Patients were divided into two
      groups. In Group I (n=78) GCS at admission was > or = 9. Seven patients presented
      with isolated TIHC and one with an associated supratentorial lesion. Three
      patients exhibited an evolving clinico-radiological course. In Group II patients
      (n=10) GCS at admission was < or = 7. All but one presented with severe
      supratentorial lesions and associated brainstem signs. RESULTS: In group I six
      patients had their TIHC managed conservatively, and two were operated on, and all
      recovered completely. In group II, two patients were operated on. The outcome was
      poor in 90% of cases. CONCLUSIONS: TIHC constitute a protean clinico-pathological
      entity. Non-comatose patients with intracerebellar clots less than 3 cm in
      diameter should be treated conservatively and expected to make a good recovery.
      Surgery is indicated for larger hematomas causing cisternal and IV ventricle
      compression ab initio or as a result of their secondary evolution. In severely
      ill patients admitted comatose, it is generally the primary brain stem damage and
      the concomitant severe supratentorial lesions to dictate the prognosis. In these
      cases obliteration of the posterior fossa cisterns is the most reliable indicator
      of poor outcome.

PMID- 11466506
TI  - Diaphragma sellae meningiomas. Report of two cases and a review of the
      literature.
AB  - Diaphragma sellae meningiomas are very rare and often manifest themselves with
      aspecific symptoms. Before the advent of MR, the diagnosis was very difficult or
      even impossible. For this reason they were often included in the broader category
      of suprasellar meningiomas. We describe two cases of diaphragma sellae
      meningiomas anterior to the pituitary stalk, manifesting with visual
      disturbances. We present the clinic and diagnostic data and we compare our
      experience with that reported in the literature. The tumor were removed by
      pterional (case 1) and subfrontal approach (case 2) with a recover of vision. Our
      experience support a clear demarcation of the diaphragma sellae meningioma among
      the wither group of suprasellar meningiomas. It is mandatory to define its
      position relative to the pituitary stalk and to the diaphragma sellae to chose
      the best surgical approach.

PMID- 11466507
TI  - Neurocysticercosis. Case report.
AB  - In the present review we report a case of a 53-year-old woman affected with a
      cyst solitary cerebral hemispheric lesion causing acute generalized seizure.
      Clinical and neuroradiologic diagnosis of cystic astrocytoma was performed and
      the patient was operated. Microscopic analysis of the surgical specimen led to a
      diagnosis of parasitic infection, consistent with neurocysticercosis (NCC). NCC
      is the most frequent parasitosis of the central nervous system (CNS) in the
      world. The infective agent is taenia solium larvae. It is endemic in Latin
      America, Africa and some Asiatic countries, such as India. In Europe, many cases
      have been reported in Portugal, Spain, Poland and Romania. In Italy NCC is a rare
      disease. In recent years no cases have been described, but with high rate of
      immigration from endemic areas (Africa and East Europe) this parasitosis will be
      found in our country too, particularly affecting communities where hygienic
      conditions are poor. In conclusion we briefly analyze the relationship between
      pathogenesis of this parasitosis and its clinical symptoms.

PMID- 11466508
TI  - Late sequelae of pontine lesions by acute uncal herniation.
AB  - The authors report the late macro- and microscopic aspects of the brainstem
      lesions found in two patients who survived an acute uncal herniation,
      respectively, 176 and 62 days. They also describe the evolution of the clinical
      picture characterized by the complete disappearance of initially present
      neurological signs but by a persistent comatose state.

PMID- 11466509
TI  - Spinal subarachnoid bleeding of unknown etiology. Case reports.
AB  - Spinal subarachnoid bleeding of unknown etiology is extremely rare. It has been
      suggested that these lesions have to be divided into two subtypes with different
      behaviour and prognosis according to their location around the spinal cord. The
      dorsally located bleeding would invariably cause severe spinal cord compression
      while the ventral lesions would have a very benign course in the absence of
      remarkable neurological deficit. We observed two patients with spontaneous spinal
      subarachnoid bleeding of unknown etiology. In both cases the disease was revealed
      by the sudden onset of severe back pain without subsequent signs of spinal cord
      compression. In one case the bleeding was ventral to the spinal cord while in the
      other it was located dorsally. The patients were evaluated with panspinal MRI and
      selective spinal angiography. They were treated conservatively and follow-up
      examinations at 18 and 24 months show they are neurologically intact in the
      absence of rebleeding episodes. We think the diagnosis of spontaneous
      subarachnoid bleeding of unknown etiology cannot be achieved without a panspinal
      MRI and a selective angiography have ruled out any other causes. We suggest their
      incidence is more prevalent than reported due to the difficulty/reluctance to
      employ MR in the presence of only minor symptoms. Our cases also show that these
      lesions may have a benign course independently from their location around the
      spinal cord.

PMID- 11466510
TI  - Isolated hemangioblastoma of the filum terminale. Case report.
AB  - The filum terminale is an exceptional location for isolated hemangioblastoma.
      Only five cases are reported in literature, prior to the magnetic resonance
      imaging era. A 57-year-old man was referred to our Department with a prolonged
      history of progressive back pain, particularly severe when recumbent, and
      recurrent unilateral sciatalgia. Computed tomography demonstrated a non
      homogeneous mass at L4 level. Magnetic resonance imaging displayed earliness and
      homogeneous enhancement of the mass with tortuous vessels above the rostral pole
      of the tumour, suggesting the diagnosis of a vascular tumour. The tumour was
      totally removed. Histological examination confirmed the hemangioblastoma
      diagnosis. The case indicates that hemangioblastoma, although uncommon, must be
      taken into consideration in cauda equina tumour diagnosis, and also emphasises
      the specificity of magnetic resonance features.

PMID- 11466511
TI  - William Twining (1790-1835): the first accurate clinical descriptions of
      "tropical sprue" and kala-azar?

PMID- 11466512
TI  - "Fingerprint" Faulds: the rehabilitation of Henry Faulds (1843-1930).

PMID- 11466513
TI  - Michael Servetus, theologian, physician and heretic: a reappraisal of his
      contribution to physiology and medicine.

PMID- 11466514
TI  - The friendship of Joseph Lister and Hector Cameron.

PMID- 11466515
TI  - William Gilbert Grace (1848-1915). Fairmount, Nottingham Lane, SE9.

PMID- 11466516
TI  - William Osler's letters from Egypt.

PMID- 11466517
TI  - Dr John Mitchell Bruce's notes relating to the last illness and death of Benjamin
      Disraeli.

PMID- 11466518
TI  - Creativity and mood disorders in nineteenth-century asylum patients.

PMID- 11466519
TI  - Catalogue of the library of Sir John Forbes (1787-1861) MD Edin FRCP Lond FRS.
      Part II: Works referring to Sir John Forbes.

PMID- 11466520
TI  - Adolf Kussmaul and his respiratory sign.

PMID- 11466521
TI  - David Livingstone (1813-1873).

PMID- 11466522
TI  - Cross-phylum regulatory potential of the ascidian Otx gene in brain development
      in Drosophila melanogaster.
AB  - The origin of molecular mechanisms of cephalic development is an intriguing
      question in evolutionary and developmental biology. Ascidians, positioned near
      the origin of the phylum Chordata, share a conserved set of anteroposterior
      patterning genes with vertebrates. Here we report the cross-phylum regulatory
      potential of the ascidian Otx gene in the development of the Drosophila brain and
      the head vertex structures. The ascidian Otx gene rescued the embryonic brain
      defect caused by a null mutation of the Drosophila orthodenticle (otd) gene and
      enhanced rostral brain development while it suppressed trunk nerve cord
      formation. Furthermore, the ascidian Otx gene restored the head vertex defects
      caused by a viable otd mutation, ocelliless, via specific activation and
      repression of downstream regulatory genes. These cross-phylum regulatory
      potentials of the ascidian Otx gene are equivalent to the activities of the
      Drosophila and human otd/Otx genes in these developmental processes. These
      results support the notion that basal chordates such as ascidians have the same
      molecular patterning mechanism for the anterior structures found in higher
      chordates, and suggest a common genetic program of cephalic development in
      invertebrate, protochordate and vertebrate.

PMID- 11466523
TI  - Ectopic expression of rice OsMADS1 reveals a role in specifying the lemma and
      palea, grass floral organs analogous to sepals.
AB  - MADS-domain-containing transcription factors play diverse roles in plant
      development. The prototypic members of this gene family are the floral organ
      identity genes of the model dicotyledonous plant, Arabidopsis thaliana. Sequence
      relatedness and function ascribe them to AP1/AGL9, AG, AP3 and PI gene groups.
      The rice MADS-box gene, OsMADS1, is a member of the AP1/ AGL9 sub-group. Tomato
      and Petunia members of this sub-group specify floral meristem identity and
      control organ development in three inner whorls. Reported here are phylogenetic
      analyses that show OsMADS1 to form a distinct clade within the AGL9 gene family.
      This sub-group currently has only three other monocot genes. We have studied the
      expression pattern of OsMADS1 and determined the consequences of its ectopic
      expression in transgenic rice plants. OsMADS1 is not expressed during panicle
      branching; earliest expression is in spikelet meristems where it is excluded from
      the outer rudimentary/sterile glumes. During organogenesis, OsMADS1 expression is
      confined to the lemma and palea, with weak expression in the carpel. Ectopic
      OsMADS1 expression results in stunted panicles with irregularly positioned
      branches and spikelets. Additionally, in spikelets, the outer rudimentary glumes
      are transformed to lemma/palea-like organs. Together, these data suggest a
      distinct role for OsMADS1 and its monocot relatives in assigning lemma/palea
      identity.

PMID- 11466524
TI  - Hremx, the ascidian homologue of ems/emx, is expressed in the anterior and
      posterior-lateral epidermis but not in the central nervous system during
      embryogenesis.
AB  - Recent comparative studies on expression patterns of homeobox genes in the
      development between ascidians and vertebrates have come to suggest a possibility
      that a common basic mechanism may exist in the patterning of the central nervous
      system (CNS). The ems/emx genes have been demonstrated to be involved in the
      formation and patterning of the anterior CNS in Drosophila and vertebrate
      embryos. In the present study, we have isolated and analyzed expression of Hremx,
      the ascidian homologue of ems/emx with particular attention to whether it is
      expressed in the larval ascidian CNS. Expression of Hremx was detected in the
      anterior trunk and lateral tail epidermis but not in the anterior CNS. The two
      expression domains of the epidermis responded in different ways upon treatment
      with retinoic acid: the anterior expression domain was unaltered, while the
      posterior expression domain extended to the anterior. The present result suggests
      that Hremx may have a function in anterior patterning but not in the patterning
      of the CNS in the ascidian embryo. We suggest the possibility that the function
      of ems/emx genes in the patterning of the anterior CNS in Drosophila and
      vertebrate embryos might have been acquired independently in the lineages to
      Drosophila and vertebrates.

PMID- 11466525
TI  - Universal occurrence of the vasa-related genes among metazoans and their germline
      expression in Hydra.
AB  - The vasa (vas)-related genes are members of the DEAD box protein family and are
      involved in germ cell formation in higher metazoans. In the present study, we
      cloned the vas-related genes as well as the PL10-related genes, other members of
      the DEAD box protein family, from lower metazoans: sponge, Hydra and planaria.
      The phylogenetic analysis suggested that the vas-related genes arose by
      duplication of a PL10-related gene before the appearance of sponges but after the
      diversion of fungi and plants. The vas-related genes in Hydra, Cnvas1 and Cnvas2
      were strongly expressed in germline cells and less strongly expressed in
      multipotent interstitial stem cells and ectodermal epithelial cells. These
      results suggest that the vas-related genes occur universally among metazoans and
      that their expression in germline cells was established at least before cnidarian
      evolution.

PMID- 11466526
TI  - Xenopus Polycomblike 2 (XPcl2) controls anterior to posterior patterning of the
      neural tissue.
AB  - A novel gene, Xenopus Polycomblike 2 (XPcl2), which encodes a protein similar to
      Drosophila Polycomblike was cloned and characterized. Polycomblike belongs to the
      Polycomb group proteins, which maintain stable expression patterns for the
      clustered homeotic genes in the Drosophila embryo by forming multimeric complexes
      on chromatin. XPcl2 shows greater amino acid sequence homology to human and mouse
      M96 (hPcl2, mPcl2) than Xenopus Pcl1 (XPcl1), mouse Tctex3 (mPcl1) and human PHF1
      (hPcl1), indicating that at least two types of Polycomblike genes are conserved
      between amphibians and mammals. XPcl2 mRNA is present both maternally and
      zygotically, and the temporal expression profile is distinct from XPcl1, another
      member of the Polycomblike family in Xenopus. XPcl2 is highly expressed in the
      anterior-dorsal region of Xenopus following the neurula stage in a manner similar
      to XPcl1. Overexpression of XPcl2 disturbs the development of the anterior
      central nervous system, eye and cement gland. In the XPcl2-overexpressing embryo,
      a hindbrain marker, Krox20, and a spinal cord marker, HoxB9, are expressed more
      posteriorly, suggesting an alteration in the anterior-posterior patterning of the
      neural tissue. In addition, XPcl2 represses Zic3- and noggin-induced anterior
      neural markers, but not neural crest markers in animal cap explants. These
      results indicate that XPcl2 regulates anterior neural tissue development and the
      anterior-posterior patterning of the neural tissue.

PMID- 11466527
TI  - Sequence and expression of the hunchback gene in Lucilia sericata: a comparison
      with other Dipterans.
AB  - We have found that the hunchback (hb)gene from Lucilia sericata is conserved in
      its functional domains in comparison with related flies, although there is
      divergence in the protein outside these regions. The expression patterns of
      Lucilia hb in early embryos are broadly similar to other higher Dipterans.
      However, in the posterior region we report blastoderm and post-gastrulation
      expression patterns, which are diverged from Musca and Drosophila. These patterns
      are reminiscent of hb expression in more primitive insects and could be
      indicative of changes in the regulation of hb in Lucilia by the terminal system.

PMID- 11466528
TI  - Zebrafish hybrids suggest genetic mechanisms for pigment pattern diversification
      in Danio.
AB  - Pigment patterns of Danio fishes are a tractable system for assessing the
      developmental genetic bases for the evolution of adult form in vertebrates. These
      pigment patterns include multiple horizontal melanophore stripes in the zebrafish
      D. rerio, a complete absence of stripes in D. albolineatus, a few broad stripes
      in D. kerri, and a combination of stripes and spots in D. nigrofasciatus. Here we
      assess the genetics of pigment pattern development and evolution using
      interspecific hybrids. We first reconstruct the phylogenetic relationships of
      these species by analyzing mitochondrial 12S and 16S rDNA sequences. We find a
      clade comprising several small species of danio, and within this clade a sister
      taxon relationship between D. rerio and D. nigrofasciatus. We also find that the
      large bodied D. dangila is more closely related to the clade of small danios than
      other large bodied species. As a first step in evaluating the genetics of pigment
      pattern diversification in the group, we then examine the phenotypes of
      interspecific hybrids. Adult pigment patterns of hybrids between D. rerio and
      other danios are in many respects more similar to D. rerio than the
      heterospecific danio, demonstrating that alleles of pigment pattern genes in
      other species typically are recessive to D. rerio alleles. Furthermore, hybrids
      between two additional striped species (D. kerri, D. nigrofasciatus) and D.
      albolineatus suggest that striped patterns are dominant or semi-dominant over an
      absence of stripes. Together, these analyses support a model in which pigment
      pattern differences between D. rerio and other species result from gain-of
      function alleles in D. rerio, or loss-of-function alleles in other danios.
      Finally, because several D. rerio pigment pattern mutants resemble heterospecific
      danios, we use interspecific complementation tests to assess potential roles for
      these loci in pigment pattern diversification. Crosses between other danios and
      most D. rerio pigment pattern mutants develop stripes, similar to control hybrids
      with wild-type D. rerio. These complementation phenotypes allow us to exclude
      most of these loci as having major effect roles in generating pigment pattern
      differences between species. In contrast, hybrids between fms mutant D. rerio and
      D. albolineatus fail to develop stripes, similar to D. albolineatus. This non
      complementation phenotype identifies changes in fms, or the pathway in which it
      acts, as candidates for contributing to the evolutionary loss of stripes in D.
      albolineatus.

PMID- 11466529
TI  - Dorsal and snail homologs in leech development.
AB  - As part of an examination of how developmental mechanisms such as axis
      specification, cell fate specification, and segmentation have evolved, we have
      cloned homologs of the Drosophila melanogaster genes dorsal and snail from the
      glossiphoniid leech Helobdella robusta. Sequences from one dorsal-class gene (Hro
      dl) and two snail-class genes (Hro-sna1 and Hro-sna2) were identified. Polyclonal
      antibodies were raised against the most conserved domains of HRO-DL and HRO-SNA1.
      Nuclear staining appeared for both proteins in mid-embryogenesis, in mesodermal
      and ectodermal precursors. During segmentation, segmentally iterated stripes of
      cells with strong HRO-DL staining appeared. The stripes of HRO-DL staining were
      first concentrated in the cytoplasm of cells, and later in the nuclei. Around
      this time, HRO-SNA levels also appeared in nuclei in segmentally iterated
      stripes. The localization of HRO-DL and HRO-SNA proteins raise the possibility
      that these genes are part of a conserved genetic pathway that, instead of
      specifying the dorsoventral axis and the mesoderm as in flies, might play a role
      in the diversification of cell types within segment primordia during leech
      development.

PMID- 11466530
TI  - Five Nkx5 genes show differential expression patterns in anlagen of sensory
      organs in medaka: insight into the evolution of the gene family.
AB  - We report the identification and characterisation of five different Nkx5-related
      genes in medaka fish (Oryzias latipes). They constitute homologues of genes
      previously isolated in higher vertebrates, Nkx5--1, Nkx5--2, Hmx1/Nkx5--3 and
      SOHo-1, and were named accordingly: OlNkx5--1.1, OlNkx5--2, OlNkx5--3 and OlSOHo.
      For the Nkx5--1 gene a new, second homologue, OlNkx5--1.2, was isolated. In
      medaka, Nkx5 and SOHo genes are differentially expressed in three developing
      sensory organs: eye, ear and lateral line and later in defined brain regions.
      Phylogenetic analyses of the entire Nkx5 family revealed that four paralogous
      Nkx5 groups, Nkx5--1, Nkx5--2, Hmx1/Nkx5--3/GH6 and SOHo, are present in
      vertebrates. Only some of the Nkx5 family members have been identified in
      singular vertebrate species so far. Here we present, for the first time, the
      isolation of representatives of each Nkx5 subgroup in one species, the medaka
      fish. Based on similarities in sequence and expression patterns, and genomic
      organisation we propose a model of the evolutionary history of the Nkx5 family.
      The model predicts that the four vertebrate Nkx5 genes arose by a tandem
      duplication, followed by chromosomal duplication. The two Nkx5--1 genes
      identified so far exclusively in medaka most probably result from an additional
      genome duplication in the fish lineage.

PMID- 11466531
TI  - Evolutionary analysis of vertebrate Notch genes.
AB  - We have conducted an evolutionary analysis of Notch genes of the vertebrates
      Danio rerio and Mus musculus to examine the expansion and diversification of the
      Notch family during vertebrate evolution. The existence of multiple Notch genes
      in vertebrate genomes suggests that the increase in Notch signaling pathways may
      be necessary for the additional complexity observed in the vertebrate body plan.
      However, orthology relationships within the vertebrate Notch family indicate that
      biological functions are not fixed within orthologous groups. Phylogenetic
      reconstruction of the vertebrate Notch family suggests that the zebrafish notch1a
      and 1b genes resulted from a duplication occurring around the time of the
      teleost/mammalian divergence. There is also evidence that the mouse Notch4 gene
      is the result of a rapid divergence from a Notch3-like gene. Investigation of the
      ankyrin repeat region sequences showed there to be little evidence for gene
      conversion events between repeat units. However, relationships between repeats 2
      5 suggest that these repeats are the result of a tandem duplication of a dual
      repeat unit. Selective pressure on maintenance of ankyrin repeat sequences
      indicated by relationships between the repeats suggests that specific repeats are
      responsible for particular biological activities, a finding consistent with
      mutational studies of the Caenorhabditis elegans gene glp-1. Sequence
      similarities between the ankyrin repeats and the region immediately C-terminal of
      the repeats further suggests that this region may be involved in the modulation
      of ankyrin repeat function.

PMID- 11466532
TI  - A gene trap insertion reveals that amyloid precursor protein expression is a very
      early event in murine embryogenesis.
AB  - Although it is known that aberrant processing of amyloid precursor protein (APP)
      in the adult is associated with Alzheimer's disease, the normal roles of APP in
      neuronal and embryonic development are not clear yet. As part of a gene trap
      screen undertaken to identify genes coding for secreted proteins involved in
      mouse gastrulation, we have obtained a mouse line in which the gene encoding APP
      is mutated by insertion of the lacZ reporter gene. This study shows that App
      expression is detected as early as gastrulation. In addition, although widely
      distributed at later stages, APP expression appears dynamically regulated during
      development.

PMID- 11466533
TI  - Expression of Xenopus L-arginine:glycine amidinotransferase (XAT) during early
      embryonic development.
AB  - We have isolated a full-length cDNA encoding Xenopus L-arginine:glycine
      amidinotransferase (XAT), which shares a highly conserved sequence with human,
      chick and rat amidinotransferase. Although there are some studies about its
      structure and function in energy metabolism of adult tissues in some other
      species, little is known about its roles during early embryonic development.
      Characterization of embryonic expression indicates that XAT is differentially
      expressed around the yolk plug including the dorsal blastopore area at early
      gastrula stages and is extensively expressed in the midline of the neural plate
      of early neurula stages. Sections reveal that its transcripts are located in the
      notochord. In the tailbud stage signals are found both in the notochord and trunk
      area, whereas only faint signals can be found in the cephalic part.

PMID- 11466534
TI  - Laser-mediated microdissection of paraffin sections from Xenopus embryos allows
      detection of tissue-specific expressed mRNAs.
AB  - One of the key end points for understanding the molecular basis of embryogenesis
      is the analysis of spatiotemporal patterns of gene expression. Methodical
      limitations due to low mRNA levels often prevent a tissue-specific resolution. In
      this study, we developed an improved laser microdissection technique and RT-PCR
      that allows marker gene detection in small tissue areas from sections of formalin
      fixed paraffin-embedded Xenopus embryos. Tissue pieces were isolated by laser
      microbeam microdissection and captured by laser pressure catapulting. Neither
      laser treatment nor conventional histological or immunochemical staining impaired
      subsequent RNA analysis. Transcripts of tissue-specific marker genes such as
      endodermin (endoderm), epidermal cytokeratin (epidermal ectoderm), N-CAM (neural
      tube), myoD (somites), and sonic hedgehog (floor plate) were amplified by nested
      RT-PCR analysis from small areas of single sections.

PMID- 11466554
TI  - Angiotensin II and cell cycle inhibition.

PMID- 11466555
TI  - JMM, past and present.

PMID- 11466556
TI  - Synaptic transmission: a story of successive successes.

PMID- 11466557
TI  - New approaches to dissect degeneracy and specificity in T cell antigen
      recognition.
AB  - The acquired immune system is a complex and very effective defense against
      invading pathogens such as bacteria and viruses. T cells are central to the
      acquired immune system by controlling B and T cell activation and induction of T
      cell effector functions. The key event for T cell activation is the recognition
      of a specific antigen by the T cell receptor. During the past decade antigen
      recognition of T cells has been investigated intensively leading to new insights
      into the molecular mechanisms of T cell activation. In addition to the resolution
      of the molecular structure of the trimolecular complex (T cell receptor, peptide,
      major histocompatibility complex) functional studies have demonstrated the
      flexibility of the T cell receptor interaction with its ligand. These
      observations have had strong implications for the understanding of T cell
      selection, maturation, and repertoire maintenance. In addition, the flexibility
      of the T cell receptor has provided the basis for novel methods to dissect
      antigen recognition and define the repertoire of ligands for a given receptor.
      Here, we summarize recent progress on T cell recognition and method innovations
      with respect to future studies in autoimmune diseases.

PMID- 11466558
TI  - Spermatogonial transplantation: the principle and possible applications.
AB  - Spermatogenesis is the process of male germ cell proliferation and
      differentiation that begins at puberty and lasts throughout life. Spermatogonia,
      especially stem spermatogonia, are the cells essential for the continued
      maintenance of spermatogenesis. Although many studies of spermatogonia have been
      performed with morphological methods, the very nature of spermatogonia still
      remains unknown. The technique of spermatogonial transplantation, developed in
      1994, made it possible to study functional aspect of spermatogonial stem cells.
      Many new developments, such as cryopreservation, xenotransplantation,
      purification, and culturing of spermatogonial stem cells, have been achieved and
      are still under investigation. The techniques could be used not only for basic
      research but also for medicine and other disciplines.

PMID- 11466559
TI  - Mechanisms for neuronal cell death and dysfunction in Huntington's disease:
      pathological cross-talk between the nucleus and the mitochondria?
AB  - Huntington's disease (HD) is a hereditary neurodegenerative condition caused by a
      characteristic mutation in the huntingtin (htt) gene. This gene was identified in
      1993. Both the mitochondria and the nucleus play an important role in HD
      pathology. However, the precise molecular mechanisms remain unclear. A key
      strategy for understanding HD pathology is to identify signaling cascades
      initiated by mutant Htt that lead to neuronal cell death and dysfunction.
      Apoptotic stress induces greater mitochondrial depolarization in HD lymphoblasts
      than in control subjects. This leads to overactivation of caspase-3, which is
      capable of cleaving htt. Truncated forms of Htt, which are similar to the caspase
      cleaved products in size, exist in the nucleus of HD patient and animal model
      brains. We hypothesize that caspases, which are activated by mitochondrial
      depolarization, play a role in producing truncated forms of Htt, which accumulate
      in the nucleus. Truncated forms of mutant Htt that accumulate in the nucleus are
      toxic to cells. There is growing evidence that truncated forms of mutant Htt in
      the nucleus influence gene transcription by binding to proteins such as CREB
      binding protein (CBP) response element binding protein binding protein, N-COR,
      glyceraldehyde-3-phosphate dehydrogenase, and p53. p53 regulates the
      transcription of various mitochondrial proteins which may underlie the
      mitochondrial abnormalities, especially the vulnerability to mitochondrial
      depolarization, seen in HD tissues. Taken together, we hypothesize a noxious
      signaling cascade between the mitochondria and the nucleus, initiated by mutant
      Htt, which may underlie HD pathology.

PMID- 11466560
TI  - Angiotensin II induces p27(Kip1) expression in renal tubules in vivo: role of
      reactive oxygen species.
AB  - Previous studies have demonstrated that angiotensin II (ANG II) mediates cell
      cycle arrest of cultured renal tubular cells by induction of p27(Kip1), an
      inhibitor of cyclin-dependent kinases. However, it is not known whether ANG II
      exerts similar effects in vivo. Infusion of ANG II into naive rats for 7 days
      increased formation of reactive oxygen species in tubular cells of the kidney.
      Furthermore, ANG II infusion stimulated protein expression of p27(Kip1) as
      detected by western blotting of tubular lysates and immunohistochemistry.
      Infusion of ANG II reduced tubular proliferation as detected by proliferating
      cell nuclear antigen (PCNA) immunohistochemistry. The increase in p27(Kip1)
      expression was not due to an increase in mRNA. Immunoprecipitation experiments
      revealed that the increased p27(Kip1) protein associates with cyclin-dependent
      kinase 2. Coadministration of the radical scavenger dimethylthiourea abolished
      this ANG II mediated p27(Kip1) expression without reducing systemic blood
      pressure. Furthermore, dimethylthiourea infusion attenuates the ANG II mediated
      G(1)-phase arrest of tubular cells. However, infusion of norepinephrine did not
      induce reactive oxygen species or p27(Kip1) expression, despite a significant
      increase in blood pressure. Thus ANG II induces p27(Kip1) expression in renal
      tubular cells in vivo. This effect is mediated by reactive oxygen species. Since
      tubular hypertrophy depends on G(1)-phase arrest and may promote subsequent
      development of interstitial fibrosis, administering oxygen radical scavenger may
      be a therapeutic tool to counteract ANG II dependent remodeling of renal tubular
      cells.

PMID- 11466561
TI  - Gender- and age-dependent relationships between the E-selectin S128R polymorphism
      and coronary artery calcification.
AB  - Development and progression of atherosclerosis involves recruitment and binding
      of circulating leukocytes to areas of inflammation within the vascular
      endothelium mediated by a diverse array of cellular adhesion molecules. A
      polymorphism in the endothelial-leukocyte adhesion molecule 1 (E-selectin) gene
      has been implicated in early-onset, angiographically defined, severe
      atherosclerotic disease because it profoundly affects ligand recognition and
      binding specificity, resulting in a significant increase in cellular adhesion.
      Relationships between the E-selectin S128R polymorphism and coronary artery
      calcification (CAC), a marker of atherosclerosis detected with noninvasive
      electron beam computed tomography, were examined in 294 asymptomatic women aged
      40--88 years and 314 asymptomatic men aged 30--80 years from the Epidemiology of
      Coronary Artery Calcification Study. The E-selectin polymorphism was not
      associated with presence of CAC in men of any age or in women over age 50. In
      women 50 years of age or younger the E-selectin polymorphism was significantly
      associated with presence of CAC after adjustment for age, body mass index,
      systolic blood pressure, ratio of total cholesterol to high-density lipoprotein
      cholesterol, and smoking. The significant association between E-selectin and CAC
      in women 50 years of age or younger may suggest that the 128R allele is a risk
      factor for coronary atherosclerosis in younger asymptomatic women, who typically
      have lower levels of traditional risk factors and reduced adhesion molecule
      expression due to the presence of higher levels of endogenous hormones.

PMID- 11466562
TI  - ASH2L: alternative splicing and downregulation during induced megakaryocytic
      differentiation of multipotential leukemia cell lines.
AB  - Abstract Drosophila ash2 is a member of the trxG gene super family, some human
      homologues of which are involved in hematopoiesis and leukemia. We report here
      the identification of the human homologue of Drosophila ash2 and its alternative
      splicing isoform, ASH2L1 and ASH2L2. ASH2L proteins are 60% homologous to
      Drosophila ash2. ASH2L also has a zinc finger motif (C2C2) although it is not
      identical to that in ASH2. Expression profile analysis showed that the amount of
      ASH2L transcripts is extremely high in fetal liver, testis, and leukemia cell
      lines with erythroid and megakaryocytic potential such as K562, Hel, and Dami. We
      treated these cells with differentiation inducers phorbol ester and hemin. We
      found that ASH2L is downregulated rapidly and dramatically in K562, Hel, and Dami
      cells during phorbol ester induced differentiation with megakaryocytic features.
      However, its expression is maintained at a high level during erythroid
      differentiation of K562 cells induced with hemin. These results suggest that
      ASH2L plays a role in hematopoiesis and is associated with some special kinds of
      leukemia.

PMID- 11466563
TI  - Serum values of proinflammatory cytokines are inversely correlated with serum
      leptin levels in patients with advanced stage cancer at different sites.
AB  - Leptin is a recently identified hormone produced by the adipocyte ob gene which
      acts as a negative feedback signal critical to the normal control of food intake
      and body weight. A number of proinflammatory cytokines, such as interleukin 6,
      tumor necrosis factor alpha, and interferon gamma, have been proposed as
      mediators of cancer cachexia; these data suggest that abnormalities in leptin
      production/release or in its feedback mechanism play a role in cancer patients.
      We therefore studied the relationship between serum leptin and serum cytokines
      interleukin 6 and tumor necrosis factor alpha levels in advanced-stage cancer
      patients. Twenty-nine advanced stage cancer patients (all but one stage IV) with
      tumors at various sites were included in the study. A direct correlation between
      body mass index and serum leptin levels was found both in cancer patients and in
      healthy individuals. The serum levels of interleukin 6 were significantly higher
      in cancer patients than in healthy individuals. In cancer patients an inverse
      correlation was found between serum levels of leptin and proinflammatory
      cytokines. There was an inverse correlation between the Eastern Cooperative
      Oncology Group performance status scale and serum levels of leptin. Regarding
      survival, patients with very high serum levels of proinflammatory cytokines and
      very low levels of leptin had very short survival. Although obtained in a cancer
      patient population not overtly cachectic, our results provide further evidence
      that a simple dysregulation of leptin production and/or release cannot be
      involved in cancer-associated pathophysiological changes leading to cachexia.

PMID- 11466564
TI  - Early inflammatory mediator response following isolated traumatic brain injury
      and other major trauma in humans.
AB  - The inflammatory response following isolated traumatic brain injury (TBI) is
      characterised by the release of pro- and anti-inflammatory mediators. In order to
      determine the important mediators regarding survival and outcome of patients with
      severe traumatic isolated head injuries, we performed this prospective
      preclinical and clinical study starting upon arrival at the site of the accident.
      After approval by the local ethics board committee, 94 multiple-injury patients
      were enrolled. Of these, 72 patients suffered from major injuries; the other 22
      patients had a severe isolated brain injury and were allotted to subsets of
      survival or nonsurvival. Of the pro- and anti-inflammatory mediators (cytokines,
      arachidonic acid metabolites and soluble adhesion molecules), interleukin-6 (IL
      6), IL-12 and malone dialdehyde (MDA) appeared to be of specific importance;
      maximum IL-6 plasma levels were eightfold higher in cases of nonsurvival than in
      those of survival. Patients that did not survive TBI were the only ones to
      express an IL-12 increase, whereas survivors and patients with other major trauma
      did not show any increase within the first 24 h. An early distinct decrease of
      MDA showed in patients who did not survive TBI, in contrast to survivor patients
      who exposed almost constant levels during the first 24 h.

PMID- 11466565
TI  - Variations in complication rates and opportunities for improvement in quality of
      care for patients having abdominal aortic surgery.
AB  - BACKGROUND: The purpose was to assess the current variation in complication rates
      and evaluate the association between specific types of complications and in
      hospital mortality and total hospital charges for patients having abdominal
      aortic surgery. PATIENTS/METHODS: We studied 2987 patients for abdominal aortic
      surgery in Maryland from 1994 to 1996 and used discharge diagnoses and procedure
      codes to identify diagnoses that most likely represent major surgery
      complications. We evaluated how in-hospital mortality and total hospital charges
      related to specific complications, adjusting for patient demographics, severity
      of illness, comorbidity, and hospital and surgeon volumes. Discharge data was
      obtained from the hospital marketing departments. RESULTS: Complication rates
      varied widely among hospitals. Complications independently associated with
      increased risk of in-hospital death include cardiac arrest with an odds ratio
      (OR) of 90 and a 95% confidence interval (CI) of 32-251, septicemia (OR 6.1, CI
      3.3-11.3), acute myocardial infarction (OR 5.7, CI 2.3-14.3), acute renal failure
      (OR 5.0, CI 2.3-11.0), surgical complications after a procedure (OR 3.1, CI 2.0
      4.9), and reoperation for bleeding (OR 2.2, CI 1.1-4.8). The population
      attributable risk for in-hospital mortality was 47% for cardiac arrest and 27%
      for acute renal failure. CONCLUSIONS: In abdominal aortic surgery on patients in
      Maryland, the rates of some complications vary widely and are independently
      associated with increased in-hospital mortality and hospital charges (charges
      differ from costs). Efforts to reduce these complications should help to decrease
      both levels.

PMID- 11466566
TI  - Simultaneous carotid artery reconstruction in patients undergoing other surgical
      interventions.
AB  - Abstract. We performed 343 vascular reconstructions of the supraaortal arteries
      from April 1996 to April 2000. Of these patients, 30 underwent combined vascular
      reconstructions - 22 combined extrathoracal and 8 combined transthoracal
      reconstructions. In 15 patients, carotid endarterectomy was combined with other
      cervical surgical interventions. In 10 patients, the vascular operation was
      combined with surgical interventions in other regions. No permanent complications
      were observed 8-52 months postoperatively, with the exception of one hemiparesis
      in the complex vascular operations. Consequently, we recommend the simultaneous
      surgical approach after careful individual assessment.

PMID- 11466567
TI  - Acute ischemia of the upper extremity: long-term results following
      thrombembolectomy with the Fogarty catheter.
AB  - OBJECTIVE: In 1962, the procedure of arterial thrombembolectomy with the Fogarty
      catheter was established. Numerous studies have been published studying
      thrombembolectomies of the lower extremities. Limited information, however, is
      available following thrombembolectomy of the upper extremity after arterial
      occlusion. The aim of the present study, therefore, was to determine long-term
      results (3-5 years after thrombembolectomy) following thrombembolectomy of the
      upper extremity with the Fogarty catheter in a large retrospective clinical
      study. DESIGN: In the present study, 251 patients were encountered. Over a period
      of 20 years, 283 thrombembolectomies with the Fogarty catheter were performed on
      the upper extremity at the surgical department of the University of Munich. MAIN
      OUTCOME MEASUREMENTS: The appearance of local and general complications in the
      postoperative phase, as well as long-term results, were evaluated. RESULTS: The
      results indicate that general complications - i.e., cardiac insufficiency,
      cerebral ischemia, etc. - occurred in 18 patients (7.2%). Local complications -
      i.e., wound infection, persistence of ischemia, or hematoma - were evident in 51
      patients (20.3%). Re-occlusion following thrombembolectomy was found in 21
      patients (8.8%). The affected extremity had to be amputated in five cases (2.0%),
      and 14 patients (5.6%) died during the postoperative phase. As a result of
      multimorbidity of the patients and average age at the time of surgery (73 years),
      40% of the patients had died before the date of examination. Nonetheless, 111
      patients of the 117 living patients showed no complaints or minor coldness and
      pain following heavy exercise. CONCLUSIONS: The results of the present study
      indicate that, in most cases, thrombembolectomy with the Fogarty catheter
      represents a successful surgical method for the acute treatment of arterial
      occlusion of the upper extremity.

PMID- 11466568
TI  - Can a coated Dacron vascular graft maintain a heparin-induced thrombocytopenia
      type II?
AB  - In the course of reconstruction of peripheral arterial occlusion processes, two
      gelatin-coated Dacron grafts and one collagen-coated Dacron patch were implanted
      in a 52-year-old male patient. Eight days following low-dose heparinization (5
      days prior to surgery, 3 days postoperatively) with unfractionated heparin, with
      no clinical symptoms present, a dramatic isolated thrombocyte depression
      occurred, from 212 Gpt/l prior to surgery to 14 Gpt/l on postoperative day 3.
      Laboratory tests verified an HIT type II [heparin-induced platelet aggregation
      assay (HIPAA) and ELISA]. Despite immediate discontinuation of heparin and
      commencement of an anticoagulant therapy with Revasc and Refludan, an 8-week
      thrombocyte depression occurred which was eliminated only temporarily by
      administration of gammaglobulin. The specific antibody tests turned out positive
      for more than 5 months. Having ruled out other causes of thrombocytopenia, we
      assume that the case presented was either due to an interaction not elucidated to
      date or triggered by the grafts (gelatin/collagen/Dacron). The manufacturers of
      the grafts have disputed a heparinoid action.

PMID- 11466569
TI  - Aortic valve replacement with or without concomitant coronary artery bypass
      grafting in the ninth decade of life.
AB  - Due to demographic changes in average life expectancy, the age of patients
      undergoing cardiac surgery is increasing. We have reviewed the short- and long
      term outcome after aortic valve replacement with or without concomitant coronary
      artery bypass grafting in patients over 80 years of age. From 1 January 1995
      until 30 June 1999, 114 patients (83 women and 31 men, 80-89 years of age, 82.8+/
      2.4 years) with symptomatic aortic valve disease underwent aortic valve
      replacement. Of these patients, 54% (group A) received isolated valve replacement
      and 46% (group B) underwent myocardial revascularization as well. The
      perioperative mortality rate was 4.8% for group A and 7.7% for group B. The 30
      day hospital mortality rate was 4.8% for group A and 15.4% for group B. The
      follow-up time ranged between 3 months and 63 months (32+/-15 months). None of
      the patients had to be reoperated for prosthetic valve dysfunction or
      endocarditis. Bleeding complications due to anticoagulation therapy were not
      observed. Of the 15 deaths during the follow-up period, seven (47%) were cardiac
      in nature and two (13%) were related to stroke. Actuarial survival rates for
      group A were 90%, 84%, and 76% at 1, 2, and 3 years, respectively, and for group
      B were 75%, 71%, and 68%. One year after the operation, permanent nursing care
      was not required by 100% of patients in group A (2 years, 98%; 3 years, 95%) and
      by 100% of patients in group B (2 years, 95%; 3 years, 91%). At a 1-year interval
      after the operation, 98% of patients in group A had not been hospitalized as a
      result of cardiac disorders (2 years, 98%; 3 years, 95%). The rates for group B
      were 90%, 85%, and 85%. Compared with younger age groups, aortic valve
      replacement in patients 80 years of age and older is associated with a distinctly
      increased mortality and morbidity. However, our data suggest that, considering
      the poor prognosis of conservative therapy of symptomatic aortic valve disease,
      functional status as well as life expectancy in this age group seem to be
      positively influenced by aortic valve replacement.

PMID- 11466570
TI  - Influence of intraperitoneal phospholipid dosage on adhesion formation and wound
      healing at different intervals after surgery.
AB  - BACKGROUND: Adjuvant therapy is needed to prevent adhesion formation as a major
      cause of postoperative morbidity and mortality. The efficacy of phospholipids
      (PLs) has been proven; however, information on dosage and drug safety are still
      outstanding. MATERIALS AND METHODS: Forty-eight Chinchilla rabbits underwent
      median laparotomy, abrasion of the peritoneum, jejunal anastomosis, and an
      electrocautery incision of the liver. The operation was completed by
      intraperitoneal administration of PLs in two different concentrations (30 mg/kg
      and 70 mg/kg body weight). In the control group, the abdomen was closed without
      additional treatment. Adhesion area, anastomotic bursting pressure, tensile
      strength of the midline incision, and healing of the liver wound were assessed on
      days 3, 5, 7, and 10, respectively. RESULTS: The mean areas of adhesions in the
      control group were slightly larger than in the PL groups after 3 days and 5 days.
      On day 7 and day 10, both PL groups presented with significantly smaller adhesion
      areas (P<0.05). In all groups, we measured equal anastomotic bursting pressures
      on the 3rd, 5th, and 10th postoperative days. After 7 days, the mean value of the
      PL 70-mg group (17.2 kPa) was significantly lower than in the other groups
      (control 22.1 kPa, PL 30 mg 20.7 kPa; P<0.05). The tensile strengths of the
      laparotomy wound measured after intervals of 5 days and 7 days were not
      statistically different. On day 3, it was reduced after 30 mg PL but enhanced
      after 70 mg PL, whereas 10 days after surgery the strength increased with the PL
      dosage. The inflammatory reparative response to hepatic injury, jejunal
      anastomosis, and midline incision was not affected by PLs as assessed by
      histological analysis. CONCLUSION: These results prove the efficacy of PLs in
      adhesion prevention in two concentrations. The findings reveal an unimpeded
      healing of anastomoses, laparotomy wounds, and liver incisions at different
      periods after surgery.

PMID- 11466571
TI  - Prognostic significance of free gastrointestinal tumor cells in peritoneal lavage
      detected by immunocytochemistry and polymerase chain reaction.
AB  - AIMS: The aim of our study was to identify tumor cells in peritoneal lavage
      comparatively with immunocytochemistry (ICC) and half-nested reverse
      transcriptase-polymerase chain reaction (RT-PCR) using carcinoembryonic antigen
      (CEA) as marker and to evaluate their prognostic significance. PATIENTS AND
      METHODS: In 75 patients who underwent surgery for a carcinoma of the colorectum
      (n=49), stomach (n=17) or pancreas (n=9) and 13 patients with an abdominal aortic
      aneurysm (control group) the abdomen was irrigated with saline solution
      immediately after laparotomy. Cells were separated by Ficoll-density
      centrifugation and divided into 2 equal volumes for ICC and RT-PCR. For ICC cells
      were spun onto slides by cytospin centrifugation and stained with a monoclonal
      antibody (mab) against CEA using the APAAP method. For RT-PCR total RNA was
      extracted from the cells, transcribed into cDNA and amplified with CEA-specific
      primers. Lavages of 13 patients with an abdominal aortic aneurysm and blood
      samples of 6 healthy donors served as controls. RESULTS: Immunostained tumor
      cells were found in peritoneal lavage in 23% (17/75) of all patients, whereas 63%
      (47/75) of patients gave a positive result by RT-PCR analysis. In the control
      group (n=13) no patient presented with tumor cells in ICC, however 5 of 13 (38%)
      showed amplified CEA-mRNA by RT-PCR, and so did one of six blood samples. Using
      ICC technique, we found significant correlations between detection rates and pT-,
      pN-, pM-categories as well as tumor stage. On the contrary, by RT-PCR significant
      correlations were observed only between pT- and pM-categories and detection
      rates. Detection of tumor cells in peritoneal lavage with both techniques was
      associated with poor prognosis. Moreover, these tumor cells are an independent
      prognostic factor and may have an influence on the development of peritoneal
      carcinomatosis. CONCLUSION: ICC is a useful method for detection of tumor cells
      in peritoneal lavage. In contrast, half-nested RT-PCR cannot be recommended, as
      the detection rates are unproportionally high, obviously as a result of CEA-mRNA
      expression in nontumor cells.

PMID- 11466572
TI  - Overexpression of phosphatidylinositol 3-kinase in human lung cancer.
AB  - BACKGROUND: This study was conducted to investigate the expression of
      phosphatidylinositol 3-kinase (PI3K) and AKT2, a downstream effector, in primary
      human lung carcinomas of different histological type. METHODS: Specimens from 105
      human lung carcinomas and their corresponding lymph nodes and liver metastases
      were examined using immunohistochemistry and Northern-blot assays to study the
      PI3K p85 and p110 subunits and the AKT2-expression patterns. RESULTS: The p85 and
      p110 subunits of PI3K were overexpressed at the protein level in 77% and 59% of
      80 primary lung carcinomas, respectively, irrespective of the histological type.
      PI3K overexpression was correlated with tumor grading. In contrast, no
      overexpression of PI3K subunits was observed in normal lung tissue and benign
      lung tumors. Consistent with these findings, upregulation of p110 mRNA
      transcripts was restricted to primary lung carcinomas. Overexpression of AKT2 was
      observed in 10% of the investigated lung tumor specimens, but in none of the
      healthy lung sections. A profound increase of PI3K expression was uniformly
      observed in lung tissue specimens and in corresponding extra-pulmonary lymph-node
      and liver metastases with low-differentiation grades. CONCLUSION: PI3K appears to
      be associated with the process of tumor-cell transformation and proliferation.
      One of its major downstream effector molecules, AKT2, which contributes to
      apoptotic cell death, was not upregulated by PI3K overexpression in primary lung
      carcinomas.

PMID- 11466573
TI  - Molecular mechanisms in the early phase of hemorrhagic shock.
AB  - Hemorrhagic shock (HS) results in the initiation of an inflammatory cascade that
      is critical for survival following successful resuscitation. We identified a
      complex sequence of molecular events including shock-dependent and reperfusion
      dependent responses that offer a new comprehensive approach for consequences of
      HS. Shock-dependent initializing mechanisms include the induction of inducible
      nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and CD14 and play a
      catalyzing role for subsequent phenotypic changes following resuscitation. The
      early immediate response genes iNOS and COX-2 promote the inflammatory response
      by the rapid and excessive production of nitric oxide (NO) and prostaglandins.
      The transcription factor hypoxia-inducible factor-1 (HIF-1) may regulate the
      induction of iNOS during the ischemic phase of shock. NO is an important
      signaling molecule which is involved in redox-sensitive mechanisms including the
      downstream activation of nuclear factor (NF)-kappaB. NO-dependent NF-kappaB
      activation promotes the induction of inflammatory cytokine expression during the
      reperfusion phase. Peroxynitrite-mediated direct toxicity and NO-mediated
      inflammatory toxicity contribute to organ injury. Patients suffering consequences
      of severe HS are susceptible to systemic inflammation, organ injury, and
      mortality if physiologic and therapeutic mechanisms are ineffective in limiting
      the activation of the inflammatory cascade.

PMID- 11466574
TI  - Comments on the publication of Korenkov M, Paul A, Sauerland S, Neugebauer E,
      Arndt M, Chevrel JP, Corcione F, Fingerhut A, Flament JB, Kux M, Matzinger A,
      Myrvold HE, Rath AM, Simmermacher RKJ (2001) Classification and surgical
      treatment of incisional hernia. Langenbeck's Arch Surg 386:65-73.

PMID- 11466575
TI  - Comments on the letter from S. Petersen and K. Ludwig concerning our paper
      "Classification and surgical treatment of the incisional hernia. Results of
      expert meeting." Langenbeck's Arch Surg 386:65-73.

PMID- 11466577
TI  - The Swedish Obese Subjects (SOS) study--rationale and results.
AB  - OBJECTIVE: Obesity is associated with increased morbidity and mortality. Several
      observational epidemiological studies have indicated that weight gain and weight
      loss, even in the obese, is also related to an increased mortality. The Swedish
      Obese Subjects (SOS) study was initiated in 1987 as an attempt to elucidate this
      paradox. DESIGN: Two thousand matched patient pairs will be followed for 10 y
      each. One pair member is surgically treated, while the other receives
      conventional obesity treatment. By February 2000, 1879 patient pairs have been
      recruited. RESULTS: The two-y weight reduction was 28+/-15 kg among the operated
      patients and 0.5+/-8.9 kg among the obese controls. After eight years the weight
      loss was 20+/-16 kg in the surgical group, while the controls had gained 0.7+/-12
      kg. Weight reductions achieved in the surgical group reduced the two-y incidence
      of diabetes 32 times as compared to the controls. After eight years there was
      still a 5-fold reduction in diabetes incidence. The two-y incidence of
      hypertension was similarly reduced 2.6 times in the surgical group. After eight
      years the incidence of hypertension was almost equal in the two study groups.
      CONCLUSION: Compared to weight stability, large intentional weight loss results
      in substantial reductions in the two-y incidence of several cardiovascular risk
      factors. After eight years there is still a reduced risk of developing diabetes
      in the surgical group, while the incidence of hypertension is equal in the two
      treatment groups. Whether intentional weight loss will reduce mortality is still
      too early to tell.

PMID- 11466578
TI  - Obesity and mental illness in a representative sample of young women.
AB  - OBJECTIVE: To investigate the relation between mental disorders and weight,
      especially obesity. DESIGN: Epidemiological study of mental disorders with a
      representative sample of young women. SUBJECTS: A total of 2064 women, age 18-25
      y, living in Dresden, Germany. MEASUREMENTS: Verbal reports of body mass index,
      structured clinical interview for psychological disorders. RESULTS: We found an
      association between psychological disorders and weight. Obese women had the
      highest rate of mental disorders overall, and they had higher rates of all
      subgroups of mental disorders, although many differences were not statistically
      significant. Most importantly, obese women suffered from an anxiety disorder
      significantly more often than women who were not obese. The observed differences
      were independent of socioeconomic status. CONCLUSIONS: In young women, obesity is
      related to increased rates of mental disorders, most notably anxiety disorders.
      Future longitudinal research will have to determine the causal relationships
      behind this correlation.

PMID- 11466579
TI  - The genetics of obesity: practical implications.
AB  - Over the past years substantial progress has been made in the molecular
      elucidation of monogenic forms of obesity both in rodents and in humans. In
      addition, several quantitive trait loci have been mapped in mice. In humans, non
      parametric linkage studies have led to the identification of relevant chromosomal
      regions, some of which have already been confirmed. In this review we focus on an
      interpretation of the heritability estimates obtained in twin, family and
      adoption studies. These estimates include both direct and indirect genetic
      effects. Non-additive genetic factors seemingly contribute even more than
      additive factors. The importance of the non-shared environment is stressed. Gene
      x gene interactions need to be considered when interpreting recent molecular
      genetic results pertaining to haplo-insufficiency mutations in the melanocortin-4
      receptor gene. We conclude by discussing the implications of the recent molecular
      findings in humans for phenotypical assessment in ongoing family studies.

PMID- 11466580
TI  - Association between polymorphisms in candidate genes and morbid obesity.
AB  - Polymorphisms in a number of candidate genes have been reported to be associated
      with obesity. We have determined the incidence of the following polymorphisms in
      the following candidate genes in a group of 388 morbid obese patients (mean body
      mass index (BMI) 52+/-8.01) who underwent gastric banding surgery: lipoprotein
      lipase (LpL) t-93 g and N291S; peroxisome proliferator receptor gamma
      (PPARgamma), P12A, P115Q and c1431t; peroxisome proliferator receptor alpha
      (PPARalpha) L162V; beta-adrenergic receptor 2 (beta-AR 2), Q27E; beta-adrenergic
      receptor 3 (beta-AR 3) W64R; uncoupling protein 1 (ucp-1), a-3826g, ucp-2, 45 bp
      insertion. Only for the ucp2 polymorphism did we find a statistically significant
      association with obesity. The beta-AR 3 W64R and ucp-1 a-3826g polymorphisms
      influenced the rate of the development of obesity and may act synergistically.

PMID- 11466581
TI  - Adiposity indices in German children and adolescents with genetically confirmed
      Prader-Willi syndrome (PWS).
AB  - BACKGROUND: Morbid obesity develops as a result of hyperphagia and compulsive
      eating behavior in patients with Prader-Willi syndrome (PWS), if caloric intake
      is not rigorously controlled. PWS-specific centile curves for adiposity indices
      constructed in the past were based on clinically diagnosed patients. With the
      advent of molecular genetic methods, allowing for an unequivocal diagnosis, new
      PWS curves based exclusively on molecularly diagnosed patients are becoming
      available, eliminating a potential diagnostic bias. OBJECTIVE: To compare fat
      distribution in molecularly confirmed German PWS patients to that of clinically
      diagnosed American PWS patients and a healthy reference population. DESIGN: Cross
      sectional anthropometric study. SUBJECTS: One hundred German patients (49 F) with
      molecularly confirmed PWS (age: <30 y). MEASUREMENTS: Triceps (subscapular)
      skinfold thickness, waist and hip circumference. RESULTS: Skinfold thickness was
      massively elevated in the majority of the molecularly confirmed German PWS
      patients compared to a healthy reference population. Whereas triceps skinfold
      thickness was in good agreement with American PWS patients, subscapular skinfold
      thickness in German girls rose earlier than in American PWS girls, indicating
      possible differences between caloric intake or the proportion of patients
      entering puberty spontaneously. Waist circumference and waist-hip ratio (n=89)
      were elevated in a relative small proportion of patients only and did not reflect
      lower abdominal fat. This may be due to the peculiar shape of many patients with
      a typical fat accumulation around the buttocks. CONCLUSIONS: In addition to body
      mass index, use of skinfold thickness is recommended for follow-up of dietary
      interventions in PWS.

PMID- 11466582
TI  - Biology of leptin--its implications and consequences for the treatment of
      obesity.
AB  - The fundamental biology of leptin and the leptin system is summarised. The
      hormone is produced in several organs, but primarily white adipose tissue, and is
      subject to acute regulation, particularly by the sympathetic nervous system.
      Leptin receptors are widely distributed, both centrally and peripherally, and
      there are several neuroendocrine targets. Although leptin is a key hormone in the
      regulation of energy balance, the biological effects of the hormone are
      extensive. Increasing leptin levels is unlikely to be an effective strategy for
      the treatment of obesity-except in those limited number of cases where there is a
      genuine deficiency of the hormone (eg in individuals with mutations of the leptin
      gene).

PMID- 11466583
TI  - Regulation of appetite: role of leptin in signalling systems for drive and
      satiety.
AB  - BACKGROUND: The healthy regulation of appetite involves a balance between
      excitatory (drive) and inhibitory (satiety) processes. For many years research
      has concentrated on the identification of signalling systems that mediate satiety
      to the relative exclusion of drive-inducing biological events. However, the so
      called long-term regulation of body weight has recently been given substance by
      the identification of a chemical signal believed to link the brain with adipose
      tissue stores. ANALYSIS: This signal, leptin, is in position to modulate the
      expression of a drive to eat. Studies on the relationship between leptin and
      perceived hunger, and on the eating behaviour of leptin-deficient individuals,
      are consistent with the intervention of leptin in a drive system. The contrast
      between the roles of leptin and serotonin in appetite regulation reflects the
      difference between drive-signalling and satiety signalling processes. CONCLUSION:
      It is proposed that leptin modulates the drive signals arising from the metabolic
      demand for energy but also shows some properties of a post-prandial satiety
      signal.

PMID- 11466584
TI  - Insulin-regulated transcription factors: molecular link between insulin
      resistance and cardiovascular risk factors.
AB  - Patients with insulin resistance and/or type 2 diabetes have a 5-fold increase in
      cardiovascular mortality rate. Therefore, it is a current issue of discussion
      that arterial hypertension, lipid disorders as well as visceral obesity are
      coronary risk factors, which might belong to a syndrome that is caused by
      decreased insulin sensitivity. Concerning a possible molecular link between
      insulin resistance, atherosclerosis and obesity, we focus in our research on
      questions looking for a molecular link between lipid metabolism, insulin action,
      and obesity at a gene regulatory level. Alterations in the structure, function
      and regulation of transcription factors appear to be such signalling steps which
      might play an essential role in the pathogenesis and therapy of cardiovascular
      risk factors associated with insulin resistance, eg the so called metabolic
      syndrome. Recent examples are members of the nuclear hormone receptor
      superfamily, eg peroxisome proliferator-activated receptor (PPAR) isoforms and
      sterol regulatory element-binding proteins (SREBPs). Beside their regulation by
      different metabolites, these transcription factors are also targets of hormones,
      like insulin and leptin, growth factors, and inflammatory signals. Therefore,
      they appear to be a point of signalling convergence at a gene regulatory level.
      Major signalling pathways coupling receptors at the cell surface for hormones,
      growth factors as well as cytokines to gene regulatory events in the nucleus are
      the MAP-kinase cascades. We have recently defined different postreceptor defects
      in these pathways in patients with clinical phenotypes corresponding to
      congenital lipoatrophy. Therefore, these studies may identify novel pathways
      which play a role in the control of body weight, insulin sensitivity and
      cardiovascular risk.

PMID- 11466585
TI  - Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in
      humans.
AB  - OBJECTIVE: Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis is
      frequently found in hyperinsulinemic subjects, such as patients with diabetes or
      abdominal obesity. Here, the question has been posed as to whether
      hyperinsulinemia increases HPA secretory activity. METHODS: We performed paired
      euglycemic and stepwise hypoglycemic (76-66-56-46 mg/dl)-clamp experiments in two
      groups (each of 15 healthy men) at different insulin infusions rates, ie, 1.5
      mU/min/kg (low-insulin condition) and 15.0 mU/min/kg (high-insulin condition).
      RESULTS: During the euglycemic clamp, the high rate insulin infusion increased
      plasma ACTH levels, whereas plasma ACTH levels remained essentially unchanged
      during the low-insulin condition (condition by time interaction, P=0.008).
      Likewise, serum cortisol levels were higher during the high- vs low-insulin
      condition (condition by time interaction, P=0.004). During the hypoglycemic
      clamp, plasma ACTH levels did not differ between the low- vs high-insulin
      condition, while serum cortisol levels were higher during the high- vs low
      insulin condition at the beginning of the clamp (plasma glucose approximately 76
      mg/dl; P=0.032). CONCLUSION: Data indicate that hyperinsulinemia acutely
      increases HPA secretory activity in healthy men. This finding appears to be
      relevant to the pathogenesis of many clinical abnormalities associated which
      diabetes and abdominal adiposity, often referred to as the metabolic syndrome.

PMID- 11466586
TI  - Effect of IGF-I administration on growth hormone secretion in obese subjects.
AB  - OBJECTIVE: The reduction of spontaneous and stimulated growth hormone (GH)
      secretion in obesity could reflect an increase of the inhibitory effect of
      insulin growth factor I (IGF-I) on somatotroph secretion. DESIGN: In the present
      study we aimed to verify the effect of low dose recombinant human IGF-I (20
      microg/kg subcutaneously (s.c.) at 0 min) on 3 h-spontaneous GH secretion (mGHc,
      0-180 min) and on the GH response to growth hormone releasing hormone (GHRH) (1
      microg/kg i.v. at+180 min) in obesity. SUBJECTS: Five obese women with abdominal
      adiposity (OB, age, mean+/-s.e.m.: 31+/-7.13 y; BMI: 32.04+/-3.69 kg/m(2)) and
      eight age-matched lean women (NW, 28.3+/-1.2 y; 20.1+/-0.5 kg/m(2)) were studied.
      RESULTS: The mGHc and GHRH-induced GH response in OB (1.0+/-0.7 microg/l; AUC(180
      270 min): 688.6+/-202.4 microg/l min, respectively) were lower than in NW (2.6+/
      0.8 microg/l, 1315.9+/-189.9 microg/l min, respectively, P<0.05). The
      administration of rhIGF-I increased circulating IGF-I levels in OB and NW to the
      same extent (339.0+/-50.39 and 420.3+/-30.5 microg/l, respectively). The rhIGF-I
      administration did not affect mGHc in OB or NW (1.1+/-0.9 and 3.2+/-1.0 microg/l,
      respectively) but inhibited (P<0.05) the GH response to GHRH in OB (324.2+/-153.1
      microg/l) and NW (730.2+/-288.1 microg/l). CONCLUSIONS: Our study shows that the
      administration of low dose rhIGF-I reduces the somatotroph responsiveness to GHRH
      in obesity as well as in normal subjects.

PMID- 11466587
TI  - Subcutaneous adipose tissue layers as a stable correlate of leptin in response to
      short term energy restriction in obese girls.
AB  - AIMS: We studied the relationship of subcutaneous adipose tissue layers (SAT
      layers) measured at 15 specified body sites with leptin before and after a weight
      loss program for three weeks. SUBJECTS AND METHODS: In 70 obese girls, SAT-layers
      were measured by means of the optical device, lipometer. Fat mass (FM) was
      estimated by means of bioelectrical impedance. RESULTS: At the beginning of the
      study, all estimates of adiposity, insulin, and SAT-layers from the upper body
      (from 1-neck to 6-lateral chest) were correlated to leptin at a P-value
      of<0.0001. Percentage FM together with SAT-layer 4-upper back and insulin
      explained 75% of the variation in leptin (P<0.0001). After three weeks, estimates
      of adiposity and leptin were reduced (all P<0.0001). Most SAT-layers were
      reduced, but SAT-layers 8-lower abdomen and 9-lower back were significantly
      increased. Changes in leptin were best explained by initial leptin, but
      percentage change (Delta) in insulin, Delta SAT-layer 1-neck, and Delta SAT-layer
      3-biceps contributed to the Delta leptin (adj. r(2)=0.47, P<0.0001). In the
      weight-reduced state, circulating leptin was best explained by three SAT-layers
      and insulin (adj. r(2)=0.67, P<0.0001). DISCUSSION: The results suggest that
      Delta changes in leptin are attributable to changes in the endocrine state and
      subcutaneous fat, and SAT-layers may serve as a stable correlate of leptin in the
      weight-reduced state.

PMID- 11466588
TI  - The role of dietary fat in the prevention and treatment of obesity. Efficacy and
      safety of low-fat diets.
AB  - BACKGROUND: Does dietary fat play a central role in weight gain and development
      of obesity? Do low-fat diets have adverse effects on blood lipids? OBJECTIVE AND
      DESIGN: To answer these questions we have reviewed the evidence linking the
      dietary fat content to energy balance and obesity, and examined the efficacy and
      safety of ad libitum low fat, high carbohydrate/protein diets in the prevention
      and management of obesity. RESULTS: Physiological studies have provided insight
      into the mechanisms by which the macronutrients differ in their effect on energy
      balance: (1) energy from fat is less satiating than energy from carbohydrate, and
      a high fat/carbohydrate ratio in the diet promotes passive overconsumption, a
      positive energy balance and weight gain in susceptible individuals; (2) fat is
      more readily absorbed from the intestine and fecal energy loss is much lower with
      a high dietary fat/carbohydrate ratio; (3) carbohydrate is more thermogenic than
      fat and energy expenditure is lower during positive energy balance produced by a
      diet with a high fat/carbohydrate ratio than during positive energy balance
      produced by a diet with a low fat/carbohydrate ratio. Randomized intervention
      studies comparing low fat diets to normal fat diets show that low fat diets
      prevent weight gain in normal weight subjects and produce weight loss in
      overweight individuals. In our meta-analysis of ad libitum low fat interventions
      we included 16 trials involving 1728 individuals. The difference in weight loss
      between intervention and control groups was 2.5 kg (95% CI, 1.5-3.5; P<0.0001).
      Weight loss was positively related to pre-treatment body weight (r=0.52, P<0.05)
      and to reduction in percentage energy as fat (0.37 kg/%, P<0.005). Extrapolated
      to a body mass index (BMI) approximately 30 kg/m(2), and assuming a 10% reduction
      in dietary fat, the predicted weight loss would be 4.4 kg (95% CI, 2.0-6.8 kg),
      which has been confirmed in subsequent studies. Newer studies have shown that
      replacing some carbohydrate with protein may enhance weight loss. CONCLUSION: The
      American Paradox, the observation that obesity prevalence is increasing despite a
      slight decrease in population dietary fat consumption, is easily explained by the
      concomitantly decreasing physical activity, which reduces fat requirements and
      counteracts the beneficial effect of a slight reduction in dietary fat. Low fat
      diets with a high content of complex carbohydrates and protein do not produce any
      adverse effect on cardiovascular risk factors when weight loss is allowed to
      occur, and they have been shown to decrease mortality among high risk subjects.

PMID- 11466589
TI  - Binge eating disorder and obesity.
AB  - Binge eating disorder (BED) was included in the DSM IV as a proposed diagnostic
      category for further study and as an example for an eating disorder not otherwise
      specified (EDNOS). BED is characterized by recurrent episodes of binge eating in
      the absence of regular compensatory behavior such as vomiting or laxative abuse.
      Related features include eating until uncomfortably full, eating when not
      physically hungry, eating alone and feelings of depression or guilt. BED is
      associated with increased psychopathology including depression and personality
      disorders. Although BED is not limited to obese individuals, it is most common in
      this group and those who seek help do so for treatment of overweight rather than
      for binge eating. In community samples, the prevalence of BED has been found to
      be 2-5%, in individuals who seek weight control treatment the prevalence is 30%.
      BED is more equal in gender ratio than bulimia nervosa. Eating disorder
      treatments such as cognitive behavior therapy (CBT) or interpersonal
      psychotherapy (IPT) improve binge eating with abstinence rates of about 50%.
      Antidepressants are also effective in reducing binge eating, though less so than
      psychotherapy. Standard weight loss treatments including bariatric surgery do not
      seem to exacerbate binge eating problems. Thus, both eating disorder and obesity
      treatments seem to be beneficial in BED. However, it is recommended today that
      treatment should first be directed at the disordered eating and associated
      psychopathology.

PMID- 11466590
TI  - The influence of body weight on food and shape attitudes in severely obese
      patients.
AB  - BACKGROUND: Cognitive restraint, binge eating, night eating, body image
      disparagement and shape overconcern describe the food and weight related
      attitudes of obese patients. POSTOPERATIVE FINDINGS: At long term follow-up after
      biliopancreatic diversion, body weight is steadily at normal or nearly normal
      levels regardless of food intake: any preoccupation for food, weight and diet are
      thereafter completely abandoned. The normalization of body shape corresponds to a
      sharp improvement in eating behavior, body image and psychological conditions.
      CONCLUSION: These results suggest that the dissatisfaction of one's somatic
      morphology and the consequent dieting account for most of the aberrant eating
      patterns in obese patients.

PMID- 11466591
TI  - Parental influences on laboratory eating behavior in obese and non-obese
      children.
AB  - OBJECTIVE: To determine parental influence on obesity, eating behavior of 80
      obese and normal weight children (aged 8-12 y) was investigated in the
      laboratory. DESIGN: A controlled repeated measurement design was used. The mother
      was either present or absent while the child was eating in the laboratory.
      MEASUREMENTS: The eating style was measured by recording cumulative eating curves
      with a universal eating monitor, using yoghurt as a standardized experimental
      meal. RESULTS: The eating behavior of obese children differed significantly from
      normal weight children only when the mother was present in the laboratory.
      Overweight children ate faster with larger bites and showed an acceleration of
      their eating rate towards the end of the meal. CONCLUSION: Such an eating style
      can be hypothesized to explain an increased calorie intake in obese children,
      promoting a positive energy balance in the long-term. The data support a learning
      model of obesity in childhood, which also has implications for family treatment.

PMID- 11466592
TI  - Quality of life after in-patient rehabilitation in children with obesity.
AB  - OBJECTIVE: Treating obesity concerns not only medical concomitants and future
      complications but also quality of life. The study was planned to investigate the
      effect of obesity and obesity treatment on quality of life in children. DESIGN:
      In the study presented, quality of life as well as psychosocial, clinical,
      sociodemographic and family related information was obtained from both children
      and their parents, at four time points by questionnaires: (1) Prior to in-patient
      rehabilitation (at home); (2) at the end of the in-patient rehabilitation (in
      clinics); (3) three months after admission into rehabilitation clinics; and (4)
      twelve months after admission into rehabilitation clinics. MEASUREMENT: Quality
      of life (QoL) was assessed in children using the revised German KINDL(R) quality
      of life questionnaire, a 24 item instrument yielding six dimensions and a total
      score as well as a chronic generic and an obesity module. Psychosocial
      determinants included assessments of stress, emotional support, coping and
      internal locus of control as well as expectations and motivations with regard to
      the rehabilitation programme. SUBJECTS: Seven large German in-patient
      rehabilitation clinics participated in the study in which 1019 children
      participated. These children were suffering from obesity (n=584) or asthma/atopic
      dermatitis (n=330) or both (n=105). RESULTS: Children as well as parents did not
      differ across the diagnostic groups in sociodemographic and general clinical
      variables. QoL in children was dependent on age and gender with increased age
      over 13 y and female gender being associated with lower self reported QoL.
      Differences between diagnostic groups were significant, indicating higher
      impairments in QoL in children with obesity. Multiple regression analysis showed
      that stress level, coping, as well as lack of emotional support and poor global
      health explained 37% of the variance of the KINDL(R) total score at the first
      measure point in the obesity group. Predicting QoL at the end of rehabilitation
      from data collected at the beginning of the study, psychosocial variables
      explained 28% of the variance. The results indicate that QoL of children with
      obesity is affected by age and gender and can be explained by stress, coping and
      support as well as global health ratings. QoL of obese children differs from the
      QoL of children with asthma/atopic dermatitis and improves from before to after
      rehabilitation. QoL after rehabilitation is predicted by psychosocial indicators,
      health resources and strains. CONCLUSION: The results of the study suggest that
      QoL assessment in children with obesity is relevant in understanding what life is
      like for children with obesity, which aspects of their life affect their well
      being and how quality of life can be improved through rehabilitation programmes.

PMID- 11466593
TI  - Prevention of obesity--more than an intention. Concept and first results of the
      Kiel Obesity Prevention Study (KOPS).
AB  - OBJECTIVE: Obesity prevention is necessary to address the steady rise in the
      prevalence of obesity. Although all experts agree that obesity prevention has
      high priority there is almost no research in this area. The effectiveness of
      different intervention strategies is not well documented. There is also no
      structured framework for obesity prevention. DESIGN: Based on (i) our current and
      limited knowledge and (ii) the idea that prevention of childhood obesity is an
      effective treatment of adult obesity, the Kiel Obesity Prevention Study (KOPS)
      was started in 1996. Concept, intervention strategies and first results of KOPS
      are reported in this paper. KOPS is an ongoing 8 y follow-up study. We first
      enrolled a large scale cohort of 5 to 7-y-old children, providing sufficient
      baseline data. KOPS allows further analyses of the role of individual risk
      factors as well as of long-term effectiveness of different intervention
      strategies. RESULTS: From 1996 to 1999 a representative group of 2440 5 to 7-y
      old children was recruited (ie 30.2% of the total population of 5 to 7-y-old
      children examined by the school physicians) and a full data set was obtained from
      1640 children. Of the children, 340 (20.7%) were considered as overweight and
      obese, 1108 children (67.6%) were normal weight, and underweight was found in 192
      children (11.7%). Of the normal-weight children, 31% or 346 (21.1% of the total
      population) were considered to have a risk of becoming obese. Cross-sectional
      data provided evidence that (i) there is an inverse social gradient in childhood
      overweight as well as health-related behaviours and (ii) parental fatness had a
      strong influence on childhood overweight. We observed considerable changes in
      health-related behaviours within 1 y after combined "school-" and "family-based"
      interventions. Interventions aimed to improve health-related behaviours had
      significant effects on the age-dependent increases in median triceps skinfolds of
      the whole group (from 10.9 to 11.3 mm in "intervention schools" vs from 10.7 to
      13.0 mm in "control schools", P<0.01) as well as in percentage fat mass of
      overweight children (increase by 3.6 vs 0.4% per year without and with
      intervention, respectively; P<0.05). CONCLUSION: First results of KOPS are
      promising. Besides health promotion, a better school education and social support
      seem to be promising strategies for future interventions.

PMID- 11466594
TI  - Clinical aspects of obesity in childhood and adolescence--diagnosis, treatment
      and prevention.
AB  - The level of fatness at which morbidity increases is determined on an acturial
      basis. Direct measurements of body fat content, eg hydrodensitometry,
      bioimpedance or DEXA, are useful tools in scientific studies. However, body mass
      index (BMI) is easy to calculate and is frequently used to define obesity
      clinically. An increased risk of death from cardiovascular disease in adults has
      been found in subjects whose BMI had been greater than the 75th percentile as
      adolescents. Childhood obesity seems to increase the risk of subsequent morbidity
      whether or not obesity persists into adulthood. The genetic basis of childhood
      obesity has been elucidated to some extent through the discovery of leptin, the
      ob gene product, and the increasing knowledge on the role of neuropeptides such
      as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors
      (MC4R). Environmental/exogenous factors contribute to the development of a high
      degree of body fatness early in life. Twin studies suggest that approximately 50%
      of the tendency toward obesity is inherited. There are numerous disorders
      including a number of endocrine disorders (Cushing's syndrome, hypothyroidism,
      etc) and genetic syndromes (Prader-Labhard-Willi syndrome, Bardet-Biedl syndrome
      etc) that can present with obesity. A simple diagnostic algorithm allows for the
      differentiation between primary or secondary obesity. Among the most common
      sequelae of primary childhood obesity are hypertension, dyslipidemia and
      psychosocial problems. Therapeutic strategies include psychological and family
      therapy, lifestyle/behavior modification and nutrition education. The role of
      regular exercise and exercise programs is emphasized. Surgical procedures and
      drugs used as treatments for adult obesity are still not recommended for children
      and adolescents with obesity. As obesity is the most common chronic disorder in
      the industrialized societies, its impact on individual lives as well as on health
      economics has to be recognized more widely. This review is aimed towards defining
      the clinical problem of childhood obesity on the basis of current knowledge and
      towards outlining future research areas in the field of energy homoeostasis and
      food intake control.

PMID- 11466595
TI  - The false hope syndrome: unrealistic expectations of self-change.
AB  - People appear to behave paradoxically, by persisting in repeated self-change
      attempts despite previous failures. It is argued, though, that self-change
      attempts provide some initial rewards even when unsuccessful. Feelings of control
      and optimism often accompany the early stages of self-modification efforts. In
      addition, unrealistic expectations concerning the ease, speed, likely degree of
      change, and presumed benefits of changing may overwhelm the knowledge of one's
      prior failures. It is thus important to learn to distinguish between potentially
      feasible and impossible self-change goals in order to avoid overconfidence and
      false hopes leading to eventual failure and distress.

PMID- 11466596
TI  - The therapeutic challenge: behavioral changes for long-term weight maintenance.
AB  - OBJECTIVES: Long-term results of dietary and behavioral treatment of obesity fail
      to match the obese patients' expectations, as well as the professionals'
      requirements. The therapeutic challenge remains to induce behavioral changes
      during treatment which are maintained over a long period of time, thus enabling
      long-term weight maintenance. The paper develops a framework to improve lasting
      behavioral changes. RESULTS AND CONCLUSIONS: Four elements may enhance long-term
      success. First, patients' unrealistic expectations about the weight loss have to
      be modified and patients have to be supported in accepting moderate and modest
      weight losses as success. Second, behavioral change can only be achieved if
      treatment involves a long-lasting training process, which for most patients needs
      to continue more than a year. Third, behavioral and attitudinal change should be
      governed by the principle of flexible control of eating behavior, and rigid
      control should be discouraged. Forth, long-term success appears to be more
      likely, the more behavioral dimensions are involved in the process of behavioral
      change.

PMID- 11466597
TI  - The Prevention Education Program (PEP) Nuremberg: design and baseline data of a
      family oriented intervention study.
AB  - OBJECTIVE: We describe the design and baseline data of the Prevention Education
      Program (PEP), a home-based and family oriented intervention program, aimed to
      assess and improve cardiovascular risk factors in school children and their
      families during an intervention period of 10 y. DESIGN AND METHODS: At study
      entry all participants were randomized either to an intervention group (screening
      and intervention program) or to a control group (risk screening, general advice).
      Cardiovascular risk factors (hypertension, elevated lipids, smoking, obesity) as
      well as dietary behaviour are evaluated yearly using structured interview,
      physical examination, laboratory analysis, and seven-day dietary protocol.
      RESULTS: During the years 1993-1998, 3547 adults (age 36.2+/-7 y) and 3495
      children (age 6.5+/-2 y) were recruited. Adults show a high prevalence of risk
      factors: hypertension 21%; active smoking 39%, elevated LDL-cholesterol 19%; and
      obesity 42%. Children exhibit these risk factors in comparable frequency:
      hypertension 20%; passive smoking 44%; elevated LDL-cholesterol 17%; and obesity
      19%. The analysis of the dietary protocols (1926 adults, 1569 children) shows
      that both generations adhere to a diet exceeding the recommended fat intake
      (adults 38% of total energy, children 38%), while carbohydrate intake (adults 43%
      of total energy intake, children 50%) is reduced compared to NCEP-(step I)
      guidelines. CONCLUSION: The finding, that children show a prevalence of risk
      factors which is comparable to that found in adults, supports the need for an
      early beginning of intervention. Since both generations adhere to an unhealthy
      diet which contributes to cardiovascular risk, dietary intervention may be a
      promising method in primary prevention of cardiovascular risk.

PMID- 11466598
TI  - Conceptualisation and evaluation of a cognitive-behavioural training programme
      for children and adolescents with obesity.
AB  - OBJECTIVE: Obesity is common in children and adolescents with incidence rates
      increasing both nationally and internationally. Its causes are complex and
      multifaceted, and obesity is associated with high morbidity and mortality as well
      as psychological distress. Multidimensional programmes are necessary in the
      treatment of this chronic disease in order to change eating and physical activity
      habits. A cognitive-behavioural training programme was developed and evaluated.
      In combination with diet and exercise, this special group programme that includes
      well established behavioural methods, was expected to result in long-term weight
      reduction and decrease of psychological distress in connection with obesity.
      DESIGN: As part of the six week in-patient rehabilitation for children and
      adolescents at Viktoriastift in Bad Kreuznach, the three-part programme
      (experimental group, EG) was compared with a programme that differed only in the
      psychological intervention component (instead of the specific training programme
      they undertook muscle relaxation training, comparison group, CG). SUBJECTS: In
      total, 197 children and adolescents between 9 and 19 y-of-age were recruited into
      the study. MEASUREMENTS: Somatic (eg weight status), behavioural (eg eating
      behaviour) and psychological (eg quality of life) outcomes were assessed at five
      points in time: two weeks before the intervention, at the beginning and end of
      the programme, as well as six months and one year post-intervention. The study
      started in spring 1997. Main outcomes will be presented. RESULTS: Pre- vs post
      intervention-tests showed significant improvements in self-reported eating
      behaviours for the EG compared with the CG (F=6.38, P<0.05); these changes were
      independent of age and sex. The weight status measured as the percentage of
      overweight dependent on height was reduced in both groups immediately after the
      intervention and at follow-up (F=16.51, P<0.01). Reduction in the prevalence of
      obesity tended to be higher in the EG than in the CG (15% vs 10%). Self-reported
      quality of life increased from before the intervention to follow-up more in the
      EG than in the CG (F=3.27, P=0.08). In all, the acceptance of the behavioural
      patient education programme was good. CONCLUSION: In summary, evaluation results
      indicate that the cognitive-behavioural training programme is a promising
      approach to alter obesity-related habits and to reduce somatic and psychosocial
      consequences. Long-term effects after two years are expected to underscore these
      results.

PMID- 11466599
TI  - Effectiveness of behavioral and psychodynamic in-patient treatment of severe
      obesity--first results from a randomized study.
AB  - OBJECTIVE: To compare treatment effectiveness of psychodynamic and behavioral in
      patient treatment of patients with severe obesity. DESIGN: : Randomized
      longitudinal study of obese patients (BMI> or =35 kg/m(2)) randomly assigned to
      behavioral or to psychodynamic psychosomatic rehabilitation. SUBJECTS: Ninety
      eight, mostly female (88%), obese patients (age 20-64 y, BMI 36-74 kg/m(2)).
      MEASUREMENTS: Standardized self-report scales on distress (SCL-90R), eating
      behavior (FEV), interpersonal problems (IIP), body image (FKB-20), life
      satisfaction (IRES). RESULTS: During the 6 weeks of in-patient treatment patients
      lost an average of 5.4 kg (4.3%) in the behavioral (n=46) and 6.2 kg (4.7%) in
      the psychodynamic setting (n=52). In both settings, a significant improvement was
      also found for eating behavior, well-being, body image and life satisfaction.
      Weight reduction was more pronounced for those with a higher weight at onset,
      more distress in public at admission, and a longer treatment. CONCLUSION: Despite
      considerable differences in the behavioral vs psychodynamic treatment settings,
      both were equally effective. However, some common treatment elements were
      perceived differently by patients in the two settings. Analysis of the follow-up
      data will hopefully provide evidence as to which patients benefit more from which
      approach.

PMID- 11466600
TI  - Predictors of post-treatment weight reduction after in-patient behavioral
      therapy.
AB  - OBJECTIVE: The goal of the present study was to identify covariates and
      predictors of post-treatment weight reduction. To clarify the impact of the
      individual factors, we compared "winners" (losing more than 2 BMI-points in the
      follow-up period) with "losers" (gaining more than 2 BMI-points in the same
      time). DESIGN: In a questionnaire based study, we evaluated the psychological
      impact on eating behavior, general psychopathology and depressive symptoms at
      three points in time: three months prior to admission (T0), at the beginning (T1)
      and at the end of in-patient treatment (T2) as well as 6, 12, and 18 months after
      treatment (T3-T5). SUBJECTS: One hundred and thirty eight obese patients (BMI<30
      kg/m(2)) were recruited to the study. All patients participated in a multimodal
      in-patient treatment program over a period of 10 weeks. Treatment elements were
      cognitive behavioral therapy, movement therapy, and nutritional counseling. The
      aim of treatment was to regulate food intake, to minimize dysfunctional emotional
      influences on eating behavior, to enhance physical exercise and to treat comorbid
      psychiatric disorders. Twenty nine patients (13%) of the initial sample dropped
      out or were excluded during the treatment and post-treatment period. RESULTS:
      During in-patient treatment eating behavior improved and body weight decreased
      considerably in all patients. The weight reduction continued slightly in the
      follow-up period. Moreover, general psychopathology, depressive symptoms and
      eating behavior improved and remained stable during follow-up. These benefits
      were closely related to weight reduction. Neither eating behavior, nor eating
      related cognition nor psychopathology measured at T0 and T1 predicted long term
      success at T5. "Winners" as compared to "losers" at follow-up showed less
      psychopathology, less depressive symptoms and a less disturbed eating behavior.
      Already at discharge (T2), winners were less prone to eating triggered by
      external stimuli and reported fewer feelings of hunger. These differences
      predicted post-treatment weight reduction (T3-T5). CONCLUSION: Reported feelings
      of hunger and the tendency to disinhibited eating behavior measured at discharge
      were able to predict post-treatment weight reduction in our sample. Patients
      suffering from a feeling of hunger during in-patient treatment were less likely
      to show further weight reduction in the follow-up period. Similarly, reduction of
      "disinhibition" during treatment is a precondition for post-treatment weight
      loss.

PMID- 11466601
TI  - Current pharmacological approaches to the treatment of obesity.
AB  - Although comprehensive obesity treatment programmes were shown to induce weight
      loss and to improve risk factors and comorbidities, the weight reduction is
      moderate and most patients will rapidly regain weight. For these reasons, drugs
      have been developed or are in development to support and maintain weight loss. At
      present, two drugs are available for the adjunct treatment of obesity.
      Sibutramine is a centrally acting inhibitor of noradrenaline and serotonine
      reuptake, thereby decreasing caloric intake and increasing energy expenditure.
      Orlistat is a specific lipase inhibitor that impairs fat absorption, thereby
      reducing fat uptake. Both drugs have been found to be effective and safe in a
      number of clinical studies for up to two years. The current experience with these
      drugs raises questions related to the long-term efficacy with particular
      reference to cardiovascular end-points. In addition, other current and future
      pharmacological principles for weight reduction are discussed. There is no doubt
      that an evidence-based rational pharmacological treatment of obesity is still in
      an early stage.

PMID- 11466602
TI  - Selection of patients for anti-obesity surgery.
AB  - Obesity is a disease with many comorbidities, some of which increase
      perioperative risk and most of which are improved or even cured by weight loss
      effectively achieved by surgery. Since anti-obesity surgery is "behavioral
      surgery", outcome is independent of the technical performance of the operation
      and patient selection is critical. Pre- and postoperative patient education is
      more important than in other gastrointestinal surgery. For example, knowledge of
      the "Rules of eating" and the "Rules of vomiting" are essential for outcome of
      gastric restrictive surgery. Indications for bariatric surgery are evolving as
      safety is increasing and more long-term data unequivocally demonstrate its
      effectiveness, leading to adjustments downward in body mass index and minimum
      age. However, outcome predictors are lacking, though it is recognized that
      patient knowledge, psychosocial adaptation and motivational factors including
      secondary gain and other benefits to remaining obese are important. Discrepancies
      between patients' weight goals, "ideal" or healthy weight for post-obese
      individuals and realistic weight loss based on body composition and energy
      balance, contribute to subjective assessment of quality of life after bariatric
      surgery. Well-designed observational studies rather than randomized trials, which
      are both ethically and scientifically flawed, are needed to improve patient
      selection. Until valid outcome predictors have been identified, a staged approach
      to bariatric surgery entailing long-term reoperation rates of up to 30% will
      prevail.

PMID- 11466603
TI  - Results of bariatric surgery.
AB  - OBJECTIVE: To present the results of bariatric surgery performed in our hospital
      over the last ten years. DESIGN: Longitudinal, clinical intervention with obesity
      surgery. SUBJECTS: To date in our hospital we have performed bariatric surgery on
      496 patients. Ninety-seven percent of them received a restrictive method and 3% a
      combined procedure. The mean age of our patients was 39+/-9 y. The mean weight
      was 144+/-28 kg which corresponds to a mean BMI of 51+/-8 kg/m(2). The gender
      distribution is 18% male and 82% female patients. MEASUREMENTS: Success of
      surgery with early and late complications, no laboratory measurements. RESULTS:
      The early postoperative complications were the following: wound infection 3%,
      lethality 1.2%, pleural infusion 0.7% and evisceration 0.5%. The important late
      complications were pouch dilatation and stomastenosis in 18% and staple line
      disruption in 11%. Slippage of the adjustable silicone gastric banding (ASGB)
      amounted to 5% and hernias emerged in 7% of patients. A migration and band
      infection occurred in 0.7%. Reoperations were necessary in 10% of the silastic
      ring vertical gastroplasty (SRVG) and in 39% of the ASGB patients. Patients were
      followed up every two months in the first year and later, annually. Blood samples
      were taken after 25%, 50%, 75% and 100% loss of excess weight. To date, 91% of
      our patients have reached an excess weight loss of 25%. 71% lost half of their
      overweight and one third (32%) were able to reduce it by 75%. 8% of our patients
      attained normal weight. CONCLUSIONS: For long term compliance and to avoid regain
      of weight, a close follow-up is necessary. We therefore offer special care which,
      in addition to the postoperative surgical care, includes visits by dieticians,
      internists, psychologists as well as exercise therapy. Knowledge of morbid
      obesity and skill in bariatric surgery are prior conditions to avoid
      complications and for success in bariatric surgery.

PMID- 11466608
TI  - Transcriptional downregulation of ATM by EGF is defective in ataxia
      telangiectasia cells expressing mutant protein.
AB  - There is evidence that ATM plays a wider role in intracellular signalling in
      addition to DNA damage recognition and cell cycle control. In this report we show
      that activation of the EGF receptor is defective in ataxia-telangiectasia (A-T)
      cells and that sustained stimulation of cells with EGF downregulates ATM protein
      in control cells but not in A-T cells expressing mutant protein. Concomitant with
      the downregulation of ATM, DNA-binding activity of the transcription factor Sp1
      decreased in controls after EGF treatment but increased from a lower basal level
      in A-T cells to that in untreated control cells. Mutation in two Sp1 consensus
      sequences in the ATM promoter reduced markedly the capacity of the promoter to
      support luciferase activity in a reporter assay. Overexpression of anti-sense ATM
      cDNA in control cells decreased the basal level of Sp1, which in turn was
      increased by subsequent treatment of cells with EGF, similar to that observed in
      A-T cells. On the other hand full-length ATM cDNA increased the basal level of
      Sp1 binding in A-T cells, and in response to EGF Sp1 binding decreased,
      confirming that this is an ATM-dependent process. Contrary to that observed in
      control cells there was no radiation-induced change in ATM protein in EGF-treated
      A-T cells and likewise no alteration in Sp1 binding activity. The results
      demonstrate that EGF-induced downregulation of ATM (mutant) protein in A-T cells
      is defective and this appears to be due to less efficient EGFR activation and
      abnormal Sp1 regulation.

PMID- 11466609
TI  - Spontaneously immortalized cell lines obtained from adult Atm null mice retain
      sensitivity to ionizing radiation and exhibit a mutational pattern suggestive of
      oxidative stress.
AB  - The study of Ataxia-telangiectasia (A-T) has benefited significantly from mouse
      models with knockout mutations for the Atm (A-T mutation) locus. While these
      models have proven useful for in vivo studies, cell cultures from Atm null
      embryos have been reported to grow poorly and then senesce. In this study, we
      initiated primary cultures from adult ears and kidneys of Atm homozygous mice and
      found that these cultures immortalized readily without loss of sensitivity to
      ionizing radiation and other Atm related cell cycle defects. A mutational
      analysis for loss of expression of an autosomal locus showed that ionizing
      radiation had a mutagenic effect. Interestingly, some spontaneous mutants
      exhibited a mutational pattern that is characteristic of oxidative mutagenesis.
      This result is consistent with chronic oxidative stress in Atm null cells. In
      total, the results demonstrate that permanent cell lines can be established from
      the tissues of adult mice homozygous for Atm and that these cell lines will
      exhibit expected and novel consequences of this deficiency.

PMID- 11466610
TI  - Role for c-Abl and p73 in the radiation response of male germ cells.
AB  - p53 plays a central role in the induction of apoptosis of spermatogonia in
      response to ionizing radiation. In p53(-/-) testes, however, spermatogonial
      apoptosis still can be induced by ionizing radiation, so p53 independent
      apoptotic pathways must exist in spermatogonia. Here we show that the p53
      homologues p63 and p73 are present in the testis and that p73, but not p63, is
      localized in the cytoplasm of spermatogonia. Unlike p53, neither p63 nor p73
      protein levels were found to increase after a dose of 4 Gy of X-rays. Although
      p73 protein levels did not increase, its interaction with the non-receptor
      tyrosine kinase c-Abl and its phosphorylation on tyrosine residues did. c-Abl and
      p73 co-localize in the cytoplasm of spermatogonia and spermatocytes and in the
      residual bodies. Furthermore, c-Abl protein levels increase after irradiation.
      p63 was not found to co-localize or interact with c-Abl neither before nor after
      irradiation. In conclusion, in the testis ionizing radiation elevates cytoplasmic
      c-Abl that in turn interacts with p73. This may represent an additional,
      cytoplasmic, apoptotic pathway. Although less efficient than the p53 route, this
      pathway may cause spermatogonial apoptosis as observed in p53 deficient mice.

PMID- 11466611
TI  - The adenine nucleotide translocator: a target of nitric oxide, peroxynitrite, and
      4-hydroxynonenal.
AB  - Nitric oxide (NO), peroxynitrite, and 4-hydroxynonenal (HNE) may be involved in
      the pathological demise of cells via apoptosis. Apoptosis induced by these agents
      is inhibited by Bcl-2, suggesting the involvement of mitochondria in the death
      pathway. In vitro, NO, peroxynitrite and HNE can cause direct permeabilization of
      mitochondrial membranes, and this effect is inhibited by cyclosporin A,
      indicating involvement of the permeability transition pore complex (PTPC) in the
      permeabilization event. NO, peroxynitrite and HNE also permeabilize
      proteoliposomes containing the adenine nucleotide translocator (ANT), one of the
      key components of the PTPC, yet have no or little effects on protein-free control
      liposomes. ANT-dependent, NO-, peroxynitrite- or HNE-induced permeabilization is
      at least partially inhibited by recombinant Bcl-2 protein, as well as the
      antioxidants trolox and butylated hydroxytoluene. In vitro, none of the tested
      agents (NO, peroxynitrite, HNE, and tert-butylhydroperoxide) causes preferential
      carbonylation HNE adduction, or nitrotyrosylation of ANT. However, all these
      agents induced ANT to undergo thiol oxidation/derivatization. Peroxynitrite and
      HNE also caused significant lipid peroxidation, which was antagonized by
      butylated hydroxytoluene but not by recombinant Bcl-2. Transfection-enforced
      expression of vMIA, a viral apoptosis inhibitor specifically targeted to ANT,
      largely reduces the mitochondrial and nuclear signs of apoptosis induced by NO,
      peroxynitrite and HNE in intact cells. Taken together these data suggest that NO,
      peroxynitrite, and HNE may directly act on ANT to induce mitochondrial membrane
      permeabilization and apoptosis.

PMID- 11466612
TI  - Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis
      signaling.
AB  - Bcl10 was identified as a candidate gene responsible for low grade B cell
      lymphomas of mucosa-associated lymphoid tissue. Overexpression of Bcl10 in
      cultured cells was reported to promote apoptosis, however, the mechanism of
      regulation of apoptosis mediated by Bcl10 has not been demonstrated. In the
      present study, we analysed the apoptosis signaling pathway mediated by Bcl10,
      focusing on phosphorylation of Bcl10 and the dynamic interaction with its binding
      partners during apoptosis. Previously, we have demonstrated that Bcl10
      potentially interacts with the other apoptosis regulator, TNF receptor associated
      factor-2 (TRAF2) and inhibitor of apoptosis proteins (cIAPs). The present results
      showed that the complex formation of these molecules was regulated by
      phosphorylation of Bcl10, that is, phosphorylation of Bcl10 resulted in binding
      of Bcl10 to cIAPs and the dissociation of it from TRAF2. Moreover,
      hyperphosphorylation of Bcl10 enhanced apoptosis, suggesting that changes in the
      binding partners of Bcl10 were correlated to the promotion of apoptosis as
      mediated by Bcl10. Indeed, the mutant which was deleted from the binding site of
      Bcl10 for cIAPs, could not induce apoptosis. These findings indicate that Bcl10
      is a mediator of apoptosis signaling, by switching over binding to cIAPs from
      TRAF2 through the events of Bcl10 phosphorylation.

PMID- 11466613
TI  - Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression
      of multiple genes involved in RNA-, protein- and nucleotide synthesis.
AB  - To arrive at a better understanding of the effects of the glucocorticoid
      component of chemotherapy protocols on lymphocytic leukemia cells, we analysed
      early responses of T-lymphocytic leukemia cell lines Jurkat and CEM-C7, both of
      which undergo apoptosis in response to dexamethasone, via gene chips. Among genes
      identified as repressed, a notable cluster seemed to be of importance for the
      processes of transcription, mRNA splicing and protein synthesis. Consequently, we
      assessed time-resolved uptake of uridine and methionine to monitor RNA and
      protein synthesis, along with parameters quantifying apoptosis. Repression of
      uptake to about 65% of that in untreated cells preceded the first sign of
      apoptosis by several hours in both cell lines. In addition to this general
      repression of RNA and protein synthesis, several genes were found to be regulated
      that may contribute to synergistic action of glucocorticoids with other
      components of frequently used chemotherapy protocols such as antimetabolites,
      methotrexate and alkylating agents.

PMID- 11466614
TI  - Inhibition of Wilms' tumor growth by intramuscular administration of tissue
      inhibitor of metalloproteinases-4 plasmid DNA.
AB  - Extracellular matrix (ECM) degrading matrix metalloproteinases (MMPs) lead to ECM
      turnover, a key event in cancer growth and progression. The tissue inhibitors of
      matrix metalloproteinases (TIMPs) limit the activity of MMPs, which suggests
      their use for cancer gene therapy. Here we report that systemic administration of
      naked TIMP-4 DNA significantly inhibited Wilms' tumor growth in nude mice. TIMP
      4, whose expression was lost in Wilms' tumor, inhibited the growth of G401 Wilms'
      tumor cells at a concentration lower than those required for MMP inhibition. This
      inhibition was associated with internalization of exogenous recombinant TIMP-4.
      Electroporation-mediated intramuscular injection of TIMP-4 expression plasmid
      resulted in sustained plasma TIMP-4 levels and significant tumor suppression. Our
      data demonstrate a tumor suppressive effect of TIMP-4 against Wilms' tumor and
      the potential utility of intramuscular delivery of TIMP gene for treatment of
      kidney derived cancers.

PMID- 11466615
TI  - Healthy mice with an altered c-myc gene: role of the 3' untranslated region
      revisited.
AB  - c-Myc is a protooncogene involved in the control of cellular proliferation,
      differentiation and apoptosis. Like many other early response genes, regulation
      of c-myc expression is mainly controlled at the level of mRNA stability. Multiple
      cis-acting destabilizing elements have been described that are located both in
      the protein-coding region and in the 3' untranslated region (3' UTR). However, it
      is not known when they function during development and whether they act as partly
      redundant or independent elements to regulate c-myc mRNA level of expression. To
      begin to address these questions, we created a series of c-myc alleles modified
      in the 3' UTR, using homologous recombination and the Cre/loxP system, and
      analysed the consequences of these modifications in ES cells and transgenic
      animals. We found that deletion of the complete 3' UTR, including runs of Us and
      AU-rich elements proposed, on the basis of cell-culture assays, to be involved in
      the control of c-myc mRNA stability, did not alter the steady-state level of c
      myc mRNA in any of the various situations analysed in vivo. Moreover, mice
      homozygous for the 3' UTR-deleted gene were perfectly healthy and fertile. Our
      results therefore strongly suggest that the 3' UTR of c-myc mRNA does not play a
      major role in the developmental control of c-myc expression.

PMID- 11466616
TI  - P21(Cip1) induced by Raf is associated with increased Cdk4 activity in
      hematopoietic cells.
AB  - To investigate the functions of the different Raf genes in hematopoietic cell
      proliferation, the capacities of beta-estradiol-regulated Delta Raf:ER genes to
      induce cell cycle regulatory gene expression and cell cycle progression in FDC-P1
      cells were examined. Raf activation increased the expression of Cdk2, Cdk4,
      cyclin A, cyclin D, cyclin E, p21(Cip1) and c-Myc and decreased the expression of
      p27(Kip1) which are associated with G(1) progression. However only the cell
      clones with moderate Raf activation, i.e. FD/Delta Raf-1:ER and FD/Delta A
      Raf:ER, successfully underwent cell proliferation. The cell clones with the
      highest Delta Raf activity, FD/Delta B-Raf:ER, underwent apoptosis before cell
      proliferation. p21(Cip1) induced by Raf activation specifically bound with
      Cdk4/cyclin D complexes but not Cdk2/cyclin E complexes and this binding was
      associated with the increased Cdk4 activity. However, no binding of p27(Kip1)
      with either Cdk2/cyclin E or Cdk4/cyclin D was observed. Thus Raf mediated growth
      was associated with elevated p21(Cip1) expression, which may specifically bind
      with and activate Cdk4/cyclin D complexes and with decreased p27(Kip1)
      expression.

PMID- 11466617
TI  - NF-kappa B activation results in rapid inactivation of JNK in TNF alpha-treated
      Ewing sarcoma cells: a mechanism for the anti-apoptotic effect of NF-kappa B.
AB  - We recently reported that inhibition of NF-kappa B activation as a consequence of
      the overexpression of a degradation-resistant form of I kappa B alpha [I kappa B
      alpha(A32/36)] sensitized Ewing sarcoma cells to TNF alpha-induced killing. The c
      Jun N-terminal kinases (JNK) have been shown to participate in death signaling
      triggered by certain stimuli and are activated by TNF alpha. To obtain insight
      into the mechanism of the anti-apoptotic effect of NF-kappa B, we compared the
      profiles of JNK activation by TNF alpha in control cells and in cells in which NF
      kappa B activation was impaired. We show here that JNK activation was transient
      in control cells but remained elevated in I kappa B alpha(A32/36)-expressing
      cells. NF-kappa B repressed specifically the JNK pathway, since the kinetics of
      activation of the other TNF alpha-activated-MAP kinase p38 were identical in both
      cells. Prolongation of JNK activation in I kappa B alpha(A32/36)-expressing cells
      was not inhibited by the broad spectrum caspase inhibitor Z-VAD-FMK and thus was
      not the consequence of caspase activation. Pretreatment of control cells with the
      phosphatase inhibitor vanadate greatly prolonged JNK activation by TNF alpha and
      resulted in induction of apoptosis by this cytokine. Moreover, overexpression of
      a dominant-negative mutant of JNK1 decreased TNF alpha-induced apoptosis in cells
      expressing the super repressor of NF-kappa B, indicating that the sustained
      activation of JNK1 participated in death signaling triggered by TNF alpha. Our
      results provide evidence that the repression of JNK activation by NF-kappa B
      participates in the anti-apoptotic effect of this transcription factor in TNF
      alpha-treated Ewing sarcoma cells.

PMID- 11466618
TI  - Inhibition of Ku heterodimer DNA end binding activity during granulocytic
      differentiation of human promyelocytic cell lines.
AB  - The heterodimeric Ku protein (composed of the Ku 86 and Ku 70 sub-units) is a
      nuclear protein which binds to DNA termini without sequence specificity. Ku is
      the DNA-targeting component of the large catalytic sub-unit of the DNA-dependent
      protein kinase complex that is required for the repair of DNA double-strand
      breaks in mammalian cells. We studied the expression and function of Ku/DNA-PK
      during granulocytic differentiation of two human promyelocytic cell lines, HL60
      and NB4, a process associated to decreased radiation resistance. After 3 days
      exposure to differentiating agents (either all-trans-retinoic acid or DMSO), Ku
      binding to double stranded (ds)-DNA ends declined dramatically whereas Ku protein
      levels remain unchanged. The nuclear, but not cytoplasmic, fraction of
      differentiated HL60 cells extracts exhibited a heat-sensitive inhibitory activity
      towards DNA binding of recombinant Ku heterodimer. We further demonstrate that
      immunoprecipitation of Ku is impaired in extracts from differentiated cells by
      using two antibodies that recognize epitopes within the C-terminus DNA binding
      domains of Ku 70 and Ku 86 proteins. These results favor the hypothesis of a
      protein interacting with Ku that would prevent DNA binding of heterodimerized Ku
      protein by steric hindrance.

PMID- 11466619
TI  - Activation of the p21(CIP1/WAF1) promoter by bone morphogenetic protein-2 in
      mouse B lineage cells.
AB  - BMPs exert a negative growth effect on various types of cells. We have previously
      reported that BMP-2 inhibited the growth of HS-72 mouse hybridoma cells by
      inducing p21(CIP1/WAF1) expression. In the present study, we demonstrated that
      BMP-2 activated the mouse p21(CIP1/WAF1) promoter in HS-72 cells, and that a 29
      base pair (b) region of the promoter (-1928/-1900 relative to the TATA box),
      conserved between mice and humans, was responsive to BMP-2 as well as expression
      of Smad1, Smad4, and constitutively active mutants of BMP type I receptors.
      Furthermore, an oligonucleotide containing the 29-b region was found to be
      associated with Smad4 and phosphorylated Smad1 in the nuclear extract of BMP-2
      stimulated HS-72 cells. These results suggested that BMP-2 might activate
      p21(CIP1/WAF1) transcription by inducing a binding of Smad4 and Smad1 to the 29-b
      region in HS-72 cells.

PMID- 11466620
TI  - Cdc25B activity is regulated by 14-3-3.
AB  - In the G2 phase cell cycle checkpoint arrest, the cdc25-dependent activation of
      cyclin B/cdc2, a critical step in regulating entry into mitosis, is blocked.
      Studies in yeast have demonstrated that the inhibition of cdc25 function involves
      14-3-3 binding to cdc25. In humans, two cdc25 isoforms have roles in G2/M
      progression, cdc25B and cdc25C, both bind 14-3-3. Abrogating 14-3-3 binding to
      cdc25C attenuates the G2 checkpoint arrest, but the contribution of 14-3-3
      binding to the regulation of cdc25B function is unknown. Here we demonstrate that
      high level over-expression of cdc25B in G2 checkpoint arrested cells can activate
      cyclin B/cdc2 and overcome the checkpoint arrest. Mutation of the major 14-3-3
      binding site, S323, or removal of the N-terminal regulatory domain are strong
      activating mutations, increasing the efficiency with which the mutant forms of
      cdc25B not only overcome the arrest, but also initiate aberrant mitosis. We also
      demonstrate that 14-3-3 binding to the S323 site on cdc25B blocks access of the
      substrate cyclin/cdks to the catalytic site of the enzyme, thereby directly
      inhibiting the activity of cdc25B. This provides direct mechanistic evidence that
      14-3-3 binding to cdc25B can regulate its activity, thereby controlling
      progression into mitosis.

PMID- 11466621
TI  - Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer.
AB  - We report the identification of a novel human tumor associated gene, CDCP1 (Cub
      Domain Containing Protein), which was identified using representational
      difference analysis and cDNA chip technology. The gene consists of eight exons,
      the upstream region of which neither contains a TATA- nor a CCAAT-box. However, a
      CpG island is located around the transcription start, which is found in
      approximately 60% of known genes. The CDCP1 gene was mapped to chromosome 3p21
      p23 by fluorescence in situ hybridization. For expression profiling real time
      quantitative RT--PCR was performed using cell lines and laser capture
      microdissected colon cancer biopsies. CDCP1 mRNA is approximately 6 kb and highly
      overexpressed in human colon cancer and lung cancer. CDCP1 represents a putative
      transmembrane protein, containing three CUB domains in the extracellular part
      most likely involved in cell adhesion or interacting with the extracellular
      matrix.

PMID- 11466622
TI  - Radiation induces genomic instability and mammary ductal dysplasia in Atm
      heterozygous mice.
AB  - Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance
      of two defective copies of the ATM gene that includes among its stigmata
      radiosensitivity and cancer susceptibility. Epidemiological studies have
      demonstrated that although women with a single defective copy of ATM (AT
      heterozygotes) appear clinically normal, they may never the less have an
      increased relative risk of developing breast cancer. Whether they are at
      increased risk for radiation-induced breast cancer from medical exposures to
      ionizing radiation is unknown. We have used a murine model of AT to investigate
      the effect of a single defective Atm allele, the murine homologue of ATM, on the
      susceptibility of mammary epithelial cells to radiation-induced transformation.
      Here we report that mammary epithelial cells from irradiated mice with one copy
      of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced
      genomic instability and generated a 10% incidence of dysplastic mammary ducts
      when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were
      stable and formed only normal ducts. Since radiation-induced ductal dysplasia is
      a precursor to mammary cancer, the results indicate that AT heterozygosity
      increases susceptibility to radiogenic breast cancer in this murine model system.

PMID- 11466623
TI  - T cell tumorigenesis in Lmo2 transgenic mice is independent of V-D-J recombinase
      activity.
AB  - The LMO2 gene is involved in T-cell acute leukaemia (T-ALL) in children with
      chromosomal translocations t(11;14)(p13;q11) or (7;11)(q35;p13). Transgenic
      expression of Lmo2 in T cells results in clonal tumours with long latency
      indicating that mutations in other genes are required for the development of
      overt tumours. RAG V-D-J recombinase can mediate genetic transposition and thus
      might create the secondary mutations necessary for T-ALL. Tumour development was
      compared in Lmo2 transgenic mice in the presence or absence of the Rag1 gene. No
      difference was observed in the rate of tumour formation nor in tumour histology
      in Lmo2-transgenic mice with or without Rag1. We conclude that, in this model,
      RAG recombinase is not a major mediator of mutations needed for T cell
      tumorigenesis and that antigen binding to alpha-beta or to gamma-delta T cell
      receptor does not play a role in tumorigenesis. The driving force behind the
      mutational process involved in this transgenic model remains obscure.

PMID- 11466624
TI  - Frequency of fibroblast growth factor receptor 3 mutations in sporadic tumours.
AB  - Mutations in FGFR3 have been identified in several tumour types including bladder
      carcinoma, cervical carcinoma, and multiple myeloma. In bladder carcinoma, we
      recently identified FGFR3 mutations in 41% of tumours, making this the most
      frequently mutated putative oncogene identified in bladder cancer to date. We
      have now investigated the frequency of FGFR3 mutation in a panel of 125 tumours
      and 13 cell lines from various other organs. We analysed the mutation hotspots in
      exons 7, 10 and 15 by direct DNA sequencing, and found one mutation in exon 7
      (S249C) in 1/28 (3.5%) cervical tumours. Mutations were not detected in stomach,
      rectum, colon, prostate, ovarian, breast, brain, or renal tumours, nor were they
      found in any of the cell lines included in this study. We conclude that FGFR3 is
      commonly mutated in bladder carcinoma and only rarely in cervical carcinoma.
      Several tumour types appear not to possess any mutations in FGFR3, suggesting
      that these mutations are important only in the development of certain types of
      tumour.

PMID- 11466625
TI  - Oncogenic transformation induced by membrane-targeted Akt2 and Akt3.
AB  - The kinases Akt2, Akt3 and their myristylated variants, Myr-Akt2 and Myr-Akt3
      were expressed by the RCAS vector in chicken embryo fibroblasts (CEF). Myr-Akt2
      and Myr-Akt3 were strongly oncogenic, inducing multilayered foci of transformed
      cells. In contrast, wild-type Akt2 and Akt3 were only poorly transforming, their
      efficiencies of focus formation were more than 100-fold lower; foci appeared
      later and showed less multilayering. Addition of the myristylation signal not
      only enhanced oncogenic potential but also increased kinase activities. Myr-Akt2
      and Myr-Akt3 also induced hemangiosarcomas in the animal, whereas wild type Akt2
      and Akt3 were not oncogenic in vivo. Furthermore, Akt2, driven by the lck
      (lymphocyte specific kinase) promoter in transgenic mice, induced lymphomas. The
      oncogenic effects of Akt2 and Akt3 described here are indistinguishable from
      those of Akt1. The downstream targets relevant to oncogenic transformation are
      therefore probably shared by the three Akt kinases.

PMID- 11466626
TI  - Allelic imbalance on chromosome 2q and alterations of the caspase 8 gene in
      neuroblastoma.
AB  - We previously reported a high incidence of loss of heterozygosity (LOH) on
      chromosome 2q33 in neuroblastoma (NB), observed in various types of human cancers
      including lung cancer, head and neck cancer and follicular thyroid carcinoma. To
      better elucidate the role of chromosome 2q aberrations in NB, we examined common
      allelic imbalance (AI) regions on chromosome 2q in 82 NB patients using 10
      polymorphic microsatellite markers. AI on 2q was detected in 26 (32%) of 82 NB
      cases. There was a distinct common AI region between the D2S115 and D2S307
      markers on 2q33. The distance between these markers was about 2.0 cM. Recently,
      the caspase 8 and caspase 10 genes, both of which encode cystein protease, were
      mapped to chromosome 2q33. Since the common AI region on 2q33 includes the
      caspase 8 and caspase 10 genes, the alterations of these genes were examined
      further. Absent or reduced expression of caspase 8 and caspase 10 were found in
      19 (70%) of 27 and two (7%) of 27 NB cell lines by reverse transcription
      polymerase chain reaction, respectively. A missense mutation was detected at
      codon 96, GCT (Alanine) to GTT (Valine), of the caspase 8 gene in one of the NB
      cell lines lacking caspase 8 expression. Thirteen (68%) of 19 cell lines lacking
      caspase 8 expression displayed methylation of the CpG island of the caspase 8
      gene, whereas only one (13%) of eight cell lines with caspase 8 expression showed
      caspase 8 methylation (P=0.031). Furthermore, there was a significant association
      between AI at 2q33 and loss of caspase 8 expression (P=0.026). These results
      indicated that there was a tumor suppressor gene in the common AI region on
      chromosome 2q33 involved in the pathogenesis of a subset of NB. It is possible
      that the caspase 8 gene is one of the candidate tumor suppressor genes for NB and
      inactivation of this gene plays an important role in the tumorigenesis of NB
      through mainly its methylation.

PMID- 11466627
TI  - Nine novel conserved motifs in BRCA1 identified by the chicken orthologue.
AB  - The breast cancer susceptibility gene BRCA1 encodes a multifunctional protein
      that is mutated in many hereditary breast and ovarian cancers. We have cloned a
      homologue of the human BRCA1 gene from chicken; the gene encodes a 1749 amino
      acid protein that is 33% identical to human BRCA1. Phylogenetic analyses of the
      chicken and mammalian proteins indicate that the chicken gene is a bona fide
      BRCA1 orthologue, the first to be described from a non-mammal. Most of the
      chicken protein has diverged considerably from its mammalian orthologues,
      although the RING and BRCT repeat regions are highly conserved. This marked
      overall sequence divergence has allowed us to identify nine additional highly
      conserved motifs (ranging from 8--56 amino acids in length) which are likely
      important for BRCA1 function.

PMID- 11466629
TI  - Congenital syndactyly: defatting facilitates closure without skin graft.
AB  - We attempted to correct 24 syndactylies without skin grafts in 16 consecutive
      patients. Digital volume was decreased by defatting the full length of the
      fingers and the interdigital space. Closure of the zigzag incisions on both
      fingers could then be achieved with minimal tension and did not seem to be
      related to the type of flap used for commissure resurfacing. We used 2 different
      types of flap closure. We noted that defatting was a more important determinant
      of whether the wound could be closed without graft than flap configuration. The
      new type of flap may represent an improvement for web appearance but is not a
      determination for finger closure. Only a complex syndactyly involving 3 adjacent
      atrophied fingers required a skin graft for separation. The results were
      evaluated after a mean follow-up period of 22 months. Three patients had a
      complication: an intraoperative digital nerve laceration, a scar contracture, and
      a recurrence of the treated commissure due to local infection. Two patients
      needed another surgical procedure. Supple and good quality scars were observed in
      the other patients. No conspicuous change in finger contour compared with the
      nonsyndactylized fingers was observed.

PMID- 11466630
TI  - Primary shortening of the pollicized long flexor tendon in congenital
      pollicization.
AB  - Primary shortening of the flexor digitorum profundus tendon to the pollicized
      index finger was routinely performed during all congenital pollicizations over a
      3-year period. Interphalangeal joint flexion of the pollicized digit was observed
      to begin within weeks after pollicization. The rebalancing of the pollicized long
      flexor musculotendinous unit has the potential for greater long-term strength.

PMID- 11466631
TI  - Longitudinal observation of pediatric hand and wrist ganglia.
AB  - The purpose of this study was to examine the behavior of ganglia of the hand and
      wrist in young children treated without surgery. Fourteen consecutive children,
      less than 10 years of age, who presented with cysts of the hand and wrist were
      followed up by a single surgeon. The average age of the patient at the time of
      diagnosis was 38 months (range, 2 months to 9 years 3 months). The masses
      included 7 retinacular cysts, 5 volar wrist ganglia, and 2 dorsal wrist ganglia.
      These cysts had been present for an average of 3.3 months (range, 1-12 months)
      before medical advice was sought. None of the cysts were painful. Follow-up
      averaged 33 months (range, 9-112 months), with 79% of all cysts spontaneously
      resolving, the majority within a year. We believe that a child presenting with a
      benign hand lesion characteristic of a ganglion cyst should initially be treated
      by observation.

PMID- 11466632
TI  - A comparison of two techniques for digital distraction lengthening in skeletally
      immature patients.
AB  - Since 1987, 16 skeletally immature patients aged 2 to 16 years (mean, 7.9 years)
      underwent 27 digital lengthening procedures of terminal bones, 20 metacarpals and
      7 phalanges, using the distraction callotasis technique. Seven digits were
      lengthened with 2 fixator half-pins on either side of the osteotomy site (dual
      half-pin group). Twenty digits, which were too small to accommodate 4 half-pins,
      were lengthened over a longitudinal intramedullary guidewire with 1 fixator half
      pin on either side of the osteotomy site (single half-pin/K-wire group). No bone
      grafts were needed. The mean preoperative bone length in the dual half-pin group
      was 30 mm (range, 23-40 mm) and that of the single half-pin/K-wire group was 18
      mm (10-30 mm). The mean total length gained was 14 mm (9-23 mm) in the dual half
      pin group and 12 mm (6-19 mm) in the single half-pin/K-wire group. The mean
      percent lengthened was 49% (22% to 96%) in the dual half-pin group and 70% (27%
      to 136%) in the single half-pin/K-wire group. Eighteen complications occurred: 15
      in the 20 cases using the central guidewire (75%) and 3 in the 7 cases without
      the central guidewire (43%). Only 7 complications required repeat surgery. We
      conclude that the use of the single half-pin/K-wire technique allows successful
      and substantial lengthening for bones shorter than 23 mm, making correction
      surgery possible for younger children. This technique, however, has a greater
      risk for complications.

PMID- 11466633
TI  - One-bone forearm fusion for pediatric supination contracture due to neurologic
      deficit.
AB  - The purpose of this study was to review the construction of a one-bone forearm
      performed to change the position of the forearm in children with fixed supination
      deformity due to upper extremity neurologic deficit. The one-bone forearm
      arthrodesis has been previously described in treating trauma, tumors, infection,
      and congenital deformities. It has not been described to improve forearm position
      in neurologically impaired upper extremities. We retrospectively evaluated 6
      pediatric patients with upper extremity weakness and severe supination
      contracture who underwent forearm arthrodesis in neutral or slight pronation.
      Five patients achieved fusion, and 1 patient had an atrophic nonunion (17%
      nonunion rate). Average follow-up was 6 years 6 months (range 1 year 9 months to
      11 years 2 months), and all patients were satisfied with their new forearm
      position.

PMID- 11466634
TI  - Restoration of functional prehension after radial hemihand amputation in a three
      year-old child: rationale for and long-term result after great toe transfer.
AB  - Partial hand amputations are rare injuries among children, causing significant
      functional impairment. Reports on thumb reconstruction in children and adults are
      used to develop a reconstruction plan for restoring prehension. While either
      first or second toe transplantation may be indicated to restore prehension in
      adults with thumb loss, near universal reluctance to use the great toe in
      children centers around concern regarding the subsequent function and appearance
      of the foot. This report details the reconstruction of functional prehension
      after radial hemihand amputation in a 3-year-old child. Great toe transplantation
      was used and resulted in neither objective nor subjective donor site morbidity.
      The rationale for use of the great toe in this child and long-term functional
      outcome are described.

PMID- 11466635
TI  - Hemidigital resection with collateral ligament transplantation in the treatment
      of macrodactyly: a case report.
AB  - Macrodactyly is a rare congenital anomaly of the hand that is difficult to treat.
      We describe a new technique consisting of hemidigital, longitudinal, and
      transverse en bloc resection with collateral ligament transplantation to the
      proximal interphalangeal joint that we used in a case of macrodactyly. Four years
      after the procedure the digit's appearance was largely improved with preservation
      of complete motion at the proximal interphalangeal joint. Transplantation of the
      collateral ligament ensured a stable joint. Fingertip sensibility was maintained.

PMID- 11466636
TI  - The incidence and epidemiology of congenital upper limb anomalies: a total
      population study.
AB  - An 11-year total population study of Western Australia examined the prevalence
      and epidemiology of congenital upper limb anomalies. All anomalies were
      classified according to the International Federation of Surgical Societies of the
      Hand classification. We found the prevalence of babies born with upper limb
      anomalies to be 1 in 506. Forty-six percent of those affected had another nonhand
      congenital anomaly. Fifty-one percent had bilateral hand anomalies, and 17% had
      multiple different hand anomalies. The most common anomalies were failures of
      differentiation (35%), duplications (33%), and failures of formation (15%).
      Congenital upper limb anomalies were more common in boys; preterm, postterm, and
      multiple births; and older mothers. No significant differences in prevalence or
      frequency of anomalies were found between whites and nonwhites, left and right
      sides, and in babies that survived and those who died shortly after birth.

PMID- 11466637
TI  - Nerve growth factor inhibition prevents traumatic neuroma formation in the rat.
AB  - Nerve growth factor (NGF) is thought to play a role in the pathogenesis of
      neuroma formation as well as in the development of neuropathic pain. In this
      study we attempted to antagonize NGF by using trkA-IgG, an inhibitor of NGF,
      consisting of the NGF receptor linked to an immunoglobulin. It was delivered by
      an implanted osmotic pump directly to the site of a sciatic nerve transection in
      16 rats for 30 days. The animals were monitored daily for the first 2 weeks for
      evidence of auto-cannibalization (autotomy) of the denervated foot (a sign of
      neuropathic pain). Four (25%) of the 16 rats receiving trkA-IgG exhibited such
      cannibalization compared with 9 of 15 control rats (60%) that underwent an
      identical procedure but were not treated with the trkA-IgG solution. One month
      after surgery the sciatic nerves and representative dorsal root ganglia (DRG)
      from these rats were evaluated histologically. Six of the 16 experimental rats
      (38%) demonstrated histological evidence of neuroma formation compared with 12 of
      the 15 controls (80%). There were no histological differences between the DRG
      from the two groups. These results support the notion that inhibiting NGF
      following peripheral nerve injury in the rat can reduce neuroma formation and
      neuropathic pain without damaging the cell bodies of the transected neurons.

PMID- 11466638
TI  - Clinical application of intraoperative measurement of choline acetyltransferase
      activity during functioning free muscle transfer.
AB  - Intraoperative measurement of choline acetyltransferase (CAT) activity was used
      for evaluation of the functional status of donor nerves during functioning free
      muscle transfer (FFMT). Twelve patients underwent the procedure. Seven patients
      had a brachial plexus injury, 3 Volkmann's contracture, 1 chronic peroneal nerve
      injury, and 1 forearm extensor muscle loss after wide resection of soft tissue
      sarcoma. The purpose of reconstruction using FFMT was to achieve wrist extension
      in 4 patients, simultaneous elbow flexion and finger extension in 3, elbow
      flexion in 2, finger extension in 1, finger flexion in 1, and ankle extension in
      1 patient. The gracilis muscle was transferred in all cases. The donor nerves for
      FFMT that were evaluated by CAT activity included 5 spinal accessory nerves, 4
      posterior interosseous nerves, 2 anterior interosseous nerves, and 1 deep
      peroneal nerve. Fascicles with greater than 2,000 cpm CAT activity were
      considered to reliable and used as donor motor nerves. All muscles had
      reinnervation by 3.2 months (range, 2-5 months) and obtained useful recovery.
      Intraoperative measurement of CAT activity can provide direct and quantitative
      information about the functional status of donor nerves during FFMT.

PMID- 11466639
TI  - The effect of a standard activity on the size of the median nerve as determined
      by ultrasound visualization.
AB  - The purpose of this study was to determine whether a standardized hand activity
      would produce changes in the cross-sectional diameter of the median nerve.
      Ultrasound measures of proven reliability of the cross-sectional diameter of the
      median nerve in the wrist were taken. These measures were taken before activity
      and immediately after the activity, after 5 minutes, and after 10 minutes. The
      median nerves of 40 normal subjects showed an increase in cross-sectional
      diameter immediately after hand activity then returned to a size close to the
      preactivity size within 10 minutes. The cross-sectional area of the carpal canal
      did not change significantly after the hand activity was performed. Female gender
      and body mass index over 25 were associated with significantly larger size
      increases in the median nerve. This preliminary study suggests that ultrasound is
      sensitive to the effects of activity upon the hand.

PMID- 11466640
TI  - Ulnar nerve excursion and strain at the elbow and wrist associated with upper
      extremity motion.
AB  - Significant excursion of the ulnar nerve is required for unimpeded upper
      extremity motion. This study evaluated the excursion necessary to accommodate
      common motions of daily living and associated strain on the ulnar nerve. The 2
      most common sites of nerve entrapment, the cubital tunnel and the entrance of
      Guyon's canal, were studied. Five fresh-frozen, thawed transthoracic cadaver
      specimens (10 arms) were dissected and the nerve was exposed at the elbow and
      wrist only enough to be marked with a microsuture. Excursion was measured with a
      laser mounted on a Vernier caliper fixed to the bone and aligned in the direction
      of nerve motion. A Microstrain (Burlington, VT) DVRT strain device was applied to
      the nerve at both the elbow and wrist. Nerve excursion associated with motion of
      the shoulder, elbow, wrist, and fingers (measured by goniometer) was measured at
      the wrist and elbow. An average of 4.9 mm ulnar nerve excursion was required at
      the elbow to accommodate shoulder motion from 30 degrees to 110 degrees of
      abduction, and 5.1 mm was needed for elbow motion from 10 degrees to 90 degrees.
      When the wrist was moved from 60 degrees of extension to 65 degrees of flexion,
      13.6 mm excursion of the ulnar nerve was required at the wrist. When all the
      motions of the wrist, fingers, elbow, and shoulder were combined, 21.9 mm of
      ulnar nerve excursion was required at the elbow and 23.2 mm at the wrist. Ulnar
      nerve strain of 15% or greater was experienced at the elbow with elbow flexion
      and at the wrist with wrist extension and radial deviation. Any factor that
      limits excursion at these sites could result in repetitive traction of the nerve
      and possibly play a role in the pathophysiology of cubital tunnel syndrome or
      ulnar neuropathy at Guyon's canal.

PMID- 11466641
TI  - The implication of repeated versus continuous strain on nerve function in a rat
      forelimb model.
AB  - We studied the effect of repeated and continuous nerve strain using a rat
      forelimb model to investigate whether an innocuous level of strain applied
      continuously affects nerve function when applied repeatedly. We used the rat
      medial cord of the brachial plexus and assessed the effects of strain by studying
      nerve histology (blood-nerve barrier), function (grasping strength), and
      electrophysiology. Continuous stretching was applied to the rat forelimb for 1
      hour at 2 N. After this strain neither histologic analysis, grasping strength,
      nor electrophysiologic analysis revealed any effect. We then applied repeated
      strain at both 60 and 120 times per hour; after the latter strain abnormalities
      in histology, grasping strength, and nerve conduction were identified. There
      results suggest that a small nerve strain applied repeatedly results in nerve
      dysfunction. Our data may help explain the cause of nonspecific neural symptoms
      in the upper extremities of patients with no objective findings.

PMID- 11466642
TI  - Hereditary neuropathy with liability to pressure palsies mimicking multifocal
      compression neuropathy.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent
      disorder of the peripheral nervous system characterized by reversible episodes of
      sensorimotor deficits after neural compression injuries. Also known as tomaculous
      neuropathy, HNPP is further characterized ultrastructurally by multiple focal
      thickenings (tomacula) of peripheral myelin and has an autosomal dominant
      inheritance. The neuropathology of HNPP includes a partial deletion encoding the
      peripheral myelin protein 22 (PMP-22) gene on chromosome 17, resulting in
      underexpression of PMP-22. We describe multiple compression mononeuropathies in
      an individual with HNPP and report neuropathologic findings in 2 clinically
      asymptomatic family members. Diagnosis was confirmed using pulsed-field gel
      electrophoresis. We believe that this diagnosis is clinically underappreciated by
      hand surgeons and should be considered in the differential diagnosis of patients
      with atypical presentations of compression neuropathies.

PMID- 11466643
TI  - Secondary ulnar nerve palsy in adults after elbow trauma: a report of two cases.
AB  - Secondary ulnar nerve palsy, an unusual condition in which the onset of ulnar
      nerve dysfunction occurs 1 to 3 months after elbow trauma, can be the cause of
      sudden deterioration of elbow function. Initially recognized in 1899, this
      condition has not been reported often. We describe 2 patients who had no
      subjective or objective evidence of ulnar nerve dysfunction after elbow trauma
      but had a sudden loss of motion, pain, and clinical and electrophysiologic
      evidence of ulnar nerve compression at the elbow 4 to 5 weeks after trauma.
      Marked improvement occurred after ulnar nerve subcutaneous transposition and
      contracture release.

PMID- 11466644
TI  - Pyoderma gangrenosum of the hand: a case series and review of the literature.
AB  - Pyoderma gangrenosum is a rapidly developing cutaneous ulcer that is rare in the
      hand and may mimic a fulminating infection. The correct treatment is nonsurgical;
      surgery may actually incite a pathergic response worsening the condition.
      Misdiagnosis results in inappropriate treatment, unnecessary surgery, and even
      amputations. The records of 7 patients with pyoderma gangrenosum of the hand
      treated at 2 large academic medical centers between 1992 and 1999 were reviewed.
      There were 4 men and 3 women with an average age of 58 years (range, 32-81
      years). Five patients had bilateral involvement. Minor trauma preceded the
      appearance of the lesions. An associated systemic disease was found in all
      patients with ulcerative colitis being the most common (3 patients). All patients
      initially had a misdiagnosis of infection. Thirteen misdiagnoses (range, 1
      3/patient) resulted in 16 unnecessary surgeries (mean, 2.2/patient) including 4
      amputations and 2 failed skin grafts. No surgical procedure resulted in clinical
      improvement. All cultures were negative. Several physicians (mean, 5; range, 3-7)
      examined each patient before the final diagnosis of pyoderma gangrenosum, which
      was made by, or in conjunction with, a dermatologist in all cases. The average
      time to clinical improvement after correct medical treatment was initiated was 5
      days.

PMID- 11466645
TI  - Ligament reconstruction of the painful, unstable, nonarthritic thumb
      carpometacarpal joint.
AB  - Thirty-seven cases of ligament reconstruction of the nonarthritic thumb
      carpometacarpal joint were performed in 35 patients, 29 female and 6 male,
      between 1980 and 1996. Follow-up ranged from 1 to 17 years with an average of 5.2
      years. The procedure described by Eaton and Littler in which a slip of the flexor
      carpi radialis (FCR) weaved through the first metacarpal and around the abductor
      pollicis longus and FCR was used. All patients had marked pain before surgery,
      and 65% were unable to work. No patient had radiographic evidence of arthritis
      before surgery. Sixty-seven percent had excellent results, and 30% had good
      results. All but 1 had complete or nearly complete pain relief. One hundred
      percent had good stability and improved pinch strength. All patients were able to
      return to work, 94% to their prior level of performance. There was no clinical or
      x-ray evidence of osteoarthritis in any patient at final follow-up.

PMID- 11466646
TI  - Trapezial tilt: a radiographic correlation with advanced trapeziometacarpal joint
      arthritis.
AB  - Trapeziometacarpal (TMC) joint arthritis is a common and debilitating condition
      of the hand. We defined a radiographic measure of trapezial inclination
      (trapezial tilt) and found a positive correlation between an increased trapezial
      tilt and severity of TMC joint arthritis. Radiographs (Robert's views) were
      obtained from 50 pairs of normal hands to evaluate the trapezial tilt to assess
      radial inclination of the trapezium with respect to the second metacarpal. The
      trapezial tilt was also measured in 65 hands from 43 patients with various stages
      of TMC joint arthritis and compared with the normal value. The trapezial tilt for
      hands without arthritis was 42 degrees +/- 4 degrees, Eaton stages I and II was
      42 degrees +/- 4 degrees, and Eaton stages III and IV was 50 degrees +/- 4
      degrees. Trapezial tilt angles from the Eaton III and IV group were significantly
      greater than those of the normal and Eaton I and II groups. Advanced TMC joint
      arthritis (Eaton III and IV) is associated with an increased trapezial tilt. Mild
      TMC joint arthritis with an increased trapezial tilt may be treated surgically.
      We speculate that a trapezio-trapezoid and trapezio-II metacarpal arthrodesis, or
      an opening wedge osteotomy of the trapezium might arrest the progression of TMC
      joint arthritis by resetting the slope of the trapezium and decreasing the shear
      stress within the TMC joint.

PMID- 11466647
TI  - Activation patterns of the thumb muscles during stable and unstable pinch tasks.
AB  - The ability to direct forces between the thumb and fingers is important to secure
      objects in the hand. We compared the coordination of thumb musculature in key and
      opposition pinch postures between stable and unstable tasks. The unstable task
      (producing thumb-tip force wearing a beaded thimble) required well-directed
      forces; the stable task (producing thumb-tip force against a pinch meter) did
      not. Fine-wire electromyography of thumb muscles and thumb-tip force magnitudes
      were recorded. We found no statistical differences in thumb-tip force between
      postures or stable versus unstable tasks, indicating that the highest magnitudes
      of force can be accurately directed. Abductor pollicis brevis and extensor
      pollicis longus were significantly more activated in the unstable tasks,
      suggesting their importance in directing thumb-tip force. Understanding how pinch
      forces are directed might influence the choice of muscle-tendon transfers
      performed to restore function to the severely paralyzed thumb. We introduce a
      device to quantify the ability to control pinch force magnitude and direction
      simultaneously.

PMID- 11466648
TI  - Length and width of the tendinous portion of the palmaris longus: a cadaver study
      of adult Japanese.
AB  - We examined 72 forearms of 36 cadavers to measure the length and width of the
      tendinous portion of the palmaris longus in adult Japanese. The palmaris longus
      muscles were absent in both arms in 1 cadaver and in a unilateral arm in 1
      cadaver. Double palmaris longus muscles were found in 1 arm in another cadaver.
      Most cadavers had a typical palmaris longus muscle and tendon shape. The mean
      length and width of the tendons were 124.6 +/- 17.0 and 4.5 +/- 0.7 mm,
      respectively, in male specimens and 108.3 +/- 16.4 and 4.0 +/- 0.7 mm in female
      specimens, respectively. The mean lengths of the forearms were 240.0 +/- 12.6 mm
      in male specimens and 218.8 +/- 14.6 mm in female specimens. There was a
      statistically significant correlation between the lengths of the palmaris longus
      tendon and forearm. These results indicate that one can estimate the length of
      palmaris longus tendons before surgical intervention.

PMID- 11466649
TI  - Vascular anatomy of the brachioradialis rotational musculocutaneous flap.
AB  - The purpose of this 2-part vascular injection study was to (1) determine the
      sources of blood supply to the brachioradialis muscle and the distance around
      which the brachioradialis muscle flap may be rotated for local soft tissue
      reconstruction and (2) determine the fasciocutaneous vascular perfusion territory
      associated with the vascular pedicle of the brachioradialis muscle flap. Lead
      oxide injections were administered in 16 fresh frozen human upper extremity
      amputation specimens to determine the contribution of the isolated radial
      recurrent artery (RRA) and subsequent 3- and 6-cm segments of radial artery (RA)
      to a rotational brachioradialis muscle flap. The RRA perfused an average of 41%
      (range, 20% to 60%) of the brachioradialis muscle length. Selective injection of
      the RRA and the proximal 3-cm segment of the RA perfused 80% (range, 59% to 100%)
      of the muscle length, corresponding to more than 90% of muscle volume. Flap
      rotation consistently provided adequate tissue coverage to the antecubital fossa,
      the lateral elbow, and the proximal one-third volar forearm. Based on these
      findings, the fasciocutaneous perfusion territory of the isolated vascular
      pedicle was quantified by selective India ink injection studies in 10 fresh
      frozen cadaveric specimens. Consistent fasciocutaneous perfusion occurred
      directly over the muscle belly. No specimen, however, was perfused greater than
      approximately 1 cm distal to the musculocutaneous junction. This 2-part study
      defines the vascular anatomy and local utility of the brachioradialis rotational
      musculocutaneous flap.

PMID- 11466650
TI  - Corrective osteotomy for symptomatic increased ulnar tilt of the distal end of
      the radius.
AB  - Twelve wrists in 10 patients with a mean age of 23.6 years were treated for
      symptomatic increased ulnar inclination of the joint surface with corrective
      osteotomy of the radius. Diagnoses included mild ulnar dysplasia, posttraumatic
      deformity, Madelung's disease, and multiple hereditary exostosis. All patients
      had radial-sided wrist pain and an ulnarly displaced arc of radioulnar deviation.
      Preoperative radiographs showed excessive ulnar inclination of the distal radius,
      ulnar carpal translation, adaptive carpal malalignment, and frequent distal
      radioulnar joint incongruency. The patients had decreased pain and improved wrist
      function at a mean of 5.1 years (range, 2-10 years) after surgery. Average radial
      deviation changed from 3 degrees to 16 degrees and ulnar deviation from 48
      degrees to 29 degrees; flexion/extension and pronosupination remained unchanged.
      Realignment of the wrist was shown radiographically by a change of ulnar
      inclination of the radius from 33 degrees to 21 degrees, an increase in scaphoid
      height from 16.4 to 20.4 mm, and reversal of ulnar carpal translation as shown by
      an increase in lunate-covering ratio of 64% to 77%. Reduction of the ulnar
      inclination to normal values by corrective radial osteotomy restores a more
      physiologic range of motion, decreases symptomatic wrist pain, reverts adaptive
      carpal changes to normal, increases lunate coverage, and may prevent abnormal
      cartilage overload in the ulnar compartment of the wrist.

PMID- 11466651
TI  - Mechanics of the antebrachial interosseous membrane: response to shearing forces.
AB  - The interosseous membrane functions to maintain the structural integrity of the
      forearm; however, the age-related mechanical properties of the intact membrane
      are incompletely defined. The purpose of this study is to quantify the mechanical
      properties of the interosseous membrane by applying a quasi-equilibrium shearing
      force between the radius and ulna. A 5-cm section of the central (main and
      accessory bundles) fiber from 11 (5 male and 6 female) fresh-frozen cadaver arms
      (age, 74 +/- 6.9 years) was isolated with the radial and ulnar attachments,
      measured, and positioned into the testing apparatus. A shear force was applied at
      12.7 mm/min to produce a quasi-equilibrium state, and the applied force and
      elongation were monitored. The average ultimate force, ultimate strength, and
      elastic modulus were 1101 +/- 191 N, 13.98 +/- 4.85 MPa, and 135.29 +/- 41.57
      MPa, respectively. Age-related changes were also noted with an increase in
      thickness by 0.056 mm per year of age and a decrease in fiber stiffness of 4.78
      MPa/yr. The age-related mechanical properties of the intact interosseous membrane
      are necessary for modeling forearm stability in normal and pathologic conditions.
      This information is required for analysis of repair or reconstructive procedures.

PMID- 11466652
TI  - The effect of observer experience on magnetic resonance imaging interpretation
      and localization of triangular fibrocartilage complex lesions.
AB  - This study investigates the effect of experience of the interpreter on the
      ability of magnetic resonance imaging (MRI) to identify the presence and anatomic
      location of a triangular fibrocartilage complex (TFCC) lesion. Fifty-one patients
      who underwent wrist arthroscopy with preoperative MRI studies were reviewed
      retrospectively. Two radiologists with different levels of training and
      experience evaluated the MRI scans in a blinded manner. The sensitivity rates of
      the 2 observers for detection of TFCC lesions were 86% and 80%. The specificity
      rates were 96% and 80%. The accuracy rates for prediction of a TFCC tear were 83%
      and 61% for the 2 observers. The correct location of a TFCC lesion was predicted
      by the more experienced observer for 12 of 19 central, 3 of 4 radial, and 6 of 12
      peripheral lesions. The less experienced observer correctly identified 8 of 19
      central, 2 of 4 radial, and 2 of 12 peripheral tears. The overall accuracy rates
      for prediction of a TFCC lesion and its location were 69% and 37%. Our data
      indicate that the published accuracy rates for prediction of TFCC lesion location
      may be reproducible only in very specialized centers.

PMID- 11466653
TI  - Static scapholunate dissociation: a new reconstruction technique using a volar
      and dorsal approach in a cadaver model.
AB  - We used 4 fresh-frozen cadaver arms to assess a method of reconstruction we
      designed for static scapholunate dissociation. The dorsal scapholunate ligament,
      scapholunate interosseous ligament, radioscapholunate, and radioscaphocapitate
      ligaments were sectioned. Radiographs were taken before sectioning, after
      sectioning, and after reconstruction. Passive motion was also measured before
      sectioning and after the repair. The dorsal scapholunate ligament was repaired
      directly; the palmar radioscapholunate and radioscaphocapitate ligaments were
      reconstructed using a free flexor carpi radialis tendon autograft and Mitek mini
      suture anchors (1.8-mm diameter and 5.4-mm length; Mitek Products, Norwood, MA)
      for anatomic fixation. An independent board-certified hand surgeon analyzed the
      radiographs of the wrists taken before and after sectioning and after
      reconstruction. Assessment of the unsectioned wrists revealed an average
      scapholunate angle of 45 degrees. After scapholunate dissociation was created the
      average scapholunate angle was 71 degrees. Repair of the dorsal scapholunate
      ligament alone did not improve the scapholunate angle. Average scapholunate angle
      after repair of the dorsal scapholunate ligament and reconstruction of the palmar
      ligaments was 43 degrees. Average range of motion on flexion, extension, and
      radial and ulnar deviation before ligament sectioning and after reconstruction
      was unchanged at 54 degrees, 59 degrees, 19 degrees, and 40 degrees respectively.
      This technique shows an improvement in scapholunate angle on lateral radiographs,
      and passive motion remained relatively unchanged.

PMID- 11466654
TI  - Mechanical testing of bioresorbable implants for use in metacarpal fracture
      fixation.
AB  - The purpose of this study was to evaluate the mechanical properties of a
      bioresorbable plate and screw system that was developed for the treatment of
      unstable metacarpal fractures and to compare the strength and stiffness of this
      system with those of conventional titanium plates and screws. Using a 4-point
      bending test, we measured the strength and stiffness of these implants over a 12
      week period of in vitro degradation. Our data suggest that these implants provide
      stable bending strength and stiffness for 8 weeks and gradually lose their
      strength over a period of 12 weeks. Further research is necessary to determine
      whether this level of fixation is adequate to stabilize unstable metacarpal
      fractures.

PMID- 11466655
TI  - Volar A1 pulley approach for fixation of avulsion fractures of the base of the
      proximal phalanx.
AB  - Avulsion fractures of the base of the proximal phalanx associated with collateral
      ligament instability, excluding the thumb, are relatively rare. While the
      indications for surgical intervention vary, dorsal approaches have been advocated
      despite the volar location of the fracture fragment and orientation of the
      collateral ligaments. Ten patients with 11 avulsion fractures at the base of the
      proximal phalanx associated with collateral ligament instability were treated
      with open reduction and internal fixation using a volar A1 pulley approach.
      Anatomic restoration of the articular surface and collateral ligament stability
      were obtained in all patients. All fractures healed between 5 and 9 weeks
      (average, 6 weeks). After an average 19.4-month follow-up period all patients had
      full range of motion of the metacarpophalangeal joint, collateral ligament
      stability, and grip strength of at least 90% of the uninjured hand. No
      perioperative complications occurred. The average DASH score at last follow-up
      examination was 1.8 (range, 0-6). All patients were satisfied with the outcome of
      surgery. The volar A1 pulley approach is a direct and effective approach for
      reduction and fixation of avulsion fractures of the base of the proximal phalanx
      associated with collateral ligament instability.

PMID- 11466656
TI  - Hypothenar hammer syndrome after radial forearm flap harvest: a case report.
AB  - A case of acute hypothenar hammer syndrome (HHS) in a high-risk laborer in whom
      the radial artery had been surgically removed during a prior radial forearm flap
      harvest is reported. Studies estimating the true incidence of HHS among laborers
      are reviewed to define the risk of this complication. Two major risk factors must
      be considered in the assessment of a patient for radial forearm flap harvest.
      First, the risk for immediate vascular compromise is determined by using a
      standard Allen's test to assess ulnar artery contribution to hand perfusion.
      Second, the risk for future vascular compromise is determined. When patients at
      high risk for HHS are recognized the surgeon should consider other reconstructive
      alternatives. If the superficial palmar arch is patent and complete and a radial
      forearm flap is performed, postoperative activity modification and risk
      counseling should be provided.

PMID- 11466657
TI  - Plasmacytoma of the superficial radial nerve.
AB  - We report a case of a solitary plasmacytoma involving the superficial radial
      nerve.

PMID- 11466658
TI  - Extramedullary plasmacytoma of the hand: a case report.
AB  - Plasmacytoma commonly occurs as an interosseous lesion. The soft tissue variant
      of plasmacytoma has been found infrequently in the feet but not in the hands. We
      describe a 47-year-old man with extensive involvement of the flexor tendons by a
      plasmacytoma.

PMID- 11466659
TI  - Partial versus minimal medial epicondylectomy.

PMID- 11466662
TI  - The emerging role of omega-3 polyunsaturated fatty acids in the management of
      patients with IgA nephropathy.
AB  - Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis
      in the world, affects mostly young adults, and shows a widely variable clinical
      course with many patients developing progressive renal disease, culminating in
      terminal renal failure in 20% to 40% of those afflicted. Until recently, no
      treatment options have been available for IgAN. Although a cure for the disease
      remains elusive, drugs that slow disease progression are becoming available,
      including omega-3 (n-3) fatty acids. The largest long-term clinical trial
      evaluating n-3 fatty acids in high-risk patients with IgAN showed that early and
      prolonged treatment with n-3 fatty acids retards renal progression. The rationale
      for using these fats involves potential mechanisms that reduce renal inflammation
      and glomerulosclerosis, hallmarks of progressive disease.

PMID- 11466663
TI  - Serial prealbumin levels as predictors of outcomes in a retrospective cohort of
      peritoneal and hemodialysis patients.
AB  - OBJECTIVE: Although earlier research has suggested that baseline prealbumin level
      is an independent predictor of outcome among dialysis patients, the prognostic
      importance of serial prealbumin levels is less clear. The present study had 3
      objectives: first, to determine if prealbumin (a marker of visceral protein
      stores with a relatively short half-life) predicts subsequent albumin levels
      taken at least 1 month later; second, to examine the association between serial
      prealbumin levels and clinical outcome; and third, to examine the association
      between changes in prealbumin level and outcome. DESIGN: The prognostic value of
      serial prealbumin levels was examined by linear regression analysis and Cox
      hazard models in an observational cohort study using a repeated measures design
      and time-dependent covariates. SETTING: Patients were followed by a tertiary care
      center, receiving hemodialysis (HD; at either an in-center dialysis unit or one
      of several satellite units operated by the hospital) or home peritoneal dialysis
      (PD). PATIENTS: A retrospective cohort was identified consisting of 268 incident
      and prevalent chronic HD and PD patients receiving dialysis from June 1998 to
      September 1999. MAIN OUTCOME: The study examined the association between serial
      prealbumin measurements and future laboratory and clinical outcomes (albumin,
      hospitalization, and death). RESULTS: Serial prealbumin values were independent
      predictors of future albumin levels among HD patients (P =.04), but not PD
      patients. Independent predictors of hospitalization included diabetes for PD
      patients (P =.0012) and advanced age for HD patients (P =.0008). Advanced age and
      diabetes were independent predictors of death for both HD (P =.0001 and P =.0368)
      and PD patients (P =.0014 and P =.0164). Serial prealbumin values, measured as
      time-dependent covariates, did not predict hospitalization or death. Further
      analyses examined the prognostic value of changes in prealbumin and albumin
      values as time-dependent covariates. The final multivariate analysis identified
      low baseline albumin level as an independent predictor of hospitalization among
      HD patients (P =.0282), whereas low baseline prealbumin was an independent
      predictor of death for HD patients (P =.0001). Interestingly, negative changes in
      serial prealbumin measurements were also independent predictors of death among HD
      patients (P =.0025). CONCLUSION: Serial prealbumin measurements predict
      subsequent albumin values among HD patients. As well, low baseline prealbumin
      level is an independent predictor of adverse outcome among HD patients. Although
      repeated prealbumin measurements in and of themselves were of no added prognostic
      value, falling prealbumin values identified by repeated measurements were
      additional independent predictors of death. These results support the clinical
      utility of regular prealbumin monitoring among HD patients.

PMID- 11466664
TI  - Fermentable carbohydrate and digestive nitrogen excretion.
AB  - BACKGROUND: Interventions that restrict protein intake lower plasma urea
      concentration and may slow the progression of renal failure. The question arises
      whether the effect of a dietary protein restriction could be reinforced by
      enrichment of the diet with fermentable carbohydrate because these carbohydrates
      may stimulate the extra-renal route of nitrogen (N) excretion through the
      digestive route. METHODS: The influence of fermentable carbohydrate and moderate
      protein restriction on N metabolism was investigated in a rat model of renal
      failure with ablation of 70% of renal mass compared with control rats with intact
      kidneys. Animals were adapted to diets varying with respect to nondigestible
      fermentable carbohydrate (0% or 10% fructooligosaccharide [FOS]) and with respect
      to protein content (10% or 18% casein). RESULTS: Feeding FOS led to a
      considerable enlargement of the cecum (increase in contents, wall thickness, and
      blood flow). These changes resulted in a concomitant enhancement of urea N uptake
      into the cecum and a decrease in plasma urea concentration (-30%). The extent of
      urea uptake by the cecum was influenced by plasma urea level that was determined
      by the dietary protein level and by the renal function. Thus, compared with
      control rats, the rate of urea uptake by the cecum and the total N excreted by
      the uremic rats was greater under all nutritional conditions. It is noteworthy
      that, when expressed as a percentage of total N excretion, fecal N excretion
      nearly doubled in rats adapted to the low-protein diets containing FOS. These
      effects occurred in both control rats and in uremic rats, in which a 22% decrease
      in urinary N was recorded as a result of FOS in addition to the low-protein diet.
      Globally, decreasing the amount of protein in the diet and adding a fermentable
      carbohydrate led to a decrease in urinary N excretion of more than 65% in uremic
      rats. CONCLUSION: These results suggest a possible usefulness for combining
      fermentable carbohydrate, such as FOS, with a low-protein diet to increase N
      excretion through the digestive route in detriment of the renal route. This may
      represent an efficient preventive measure to relieve the renal function in case
      of renal failure.

PMID- 11466665
TI  - Serum cystatin C is an independent predictor of total homocysteine levels in
      stable Korean renal transplant recipients with normal serum creatinine.
AB  - OBJECTIVES: To examine the determinants of fasting plasma total homocysteine
      (tHcy) levels such as cystatin C, serum creatinine (SCr), estimated glomerular
      filtration rate (GFR) from Cockroft-Gault equation, albumin, plasma folate,
      vitamin B12, and pyridoxal-5'-phosphate (PLP) among Korean renal transplant
      recipients (RTR) with normal SCr levels (< or =1.4 mg/dL). DESIGN: Cross
      sectional study. SETTING: Nephrology and Transplant Service, Catholic University
      Kangnam St. Mary's Hospital, Seoul, Korea. PARTICIPANTS: Fifty-one chronic stable
      Korean RTR with normal SCr levels (< or =1.4 mg/dL) 6 months or more following
      transplantation. MEASURES: Medical record review, anthropometric measurements,
      and overnight (10 to 14 hours) fasting blood samples for measurement of plasma
      tHcy, folate, vitamin B12, PLP, SCr, albumin, and cystatin C. RESULTS: General
      linear regression model including age, gender, vitamin status, and measurements
      of renal function showed that cystatin C and folate were independent predictors
      of tHcy levels. The partial regression coefficient for folate was -0.444 (P <.01)
      and for cystatin C, it was +0.334 (P <.05). SCr, estimated GFR, vitamin B12, PLP,
      age, and gender were not independent predictors of tHcy levels in this model.
      CONCLUSION: Both cystatin C and folate status were major independent determinants
      of fasting tHcy levels in the subgroup of Korean RTR with normal SCr.

PMID- 11466666
TI  - Clinical determinants of interdialytic weight gain.
AB  - OBJECTIVE: We recently found a close relationship between high interdialytic
      weight gain (IDWG) and nutritional parameters, confirming the potential role of
      IDWG as a marker of calorie and protein intake in hemodialysis patients. In this
      population, the control of volume status to achieve the "appropriate dry weight"
      suggests a correlation between blood pressure (BP) and IDWG. The aim of our study
      was to investigate the clinical determinants of IDWG, particularly regarding
      sodium balance and nutritional intake, in a cohort of clinically stable
      hemodialysis patients. PATIENTS AND METHODS: During a 1-year period, we collected
      clinical and biological data from 32 of 75 patients who underwent dialysis at our
      Center. To investigate the dietary protein intake, calorie intake, and sodium
      intake, a dietician assessed a 3-day dietary record. Urea kinetic parameters and
      interdialytic sodium load were calculated for all patients. RESULTS: There were
      19 men and 13 women with a mean age of 71.3 +/- 13.7 years, 10 of 32 patients
      were hypertensive, and 14% were diabetics. The mean IDWG calculated during the 3
      day interval was 4.5 +/- 1.5%. Simple and multiple regression analysis showed a
      significant and positive correlation between IDWG and protein catabolic rate
      (PCR) (P <.0001). In contrast, we did not find any relationship between sodium
      load, sodium intake, and IDWG, nor between BP and IDWG. In 15 of 32 patients with
      steadily high IDWG, PCR and calorie intake were significantly higher than in
      patients with low IDWG (1.3 +/- 0.3 v 0.9 +/- 0.3 g/kg/d, P <.0001, respectively;
      28 +/- 7.5 v 21.6 +/- 6.4 cal/kg/d, P <.02, respectively). No changes were found
      in sodium load and sodium intake. CONCLUSIONS: We confirm that, in hemodialysis
      patients, a stable IDWG may be a useful clinical marker of adequate calorie and
      protein intake. IDWG does not seem directly related to BP, even in hypertensive
      patients, suggesting that additional factors play a role in the control of BP in
      this population.

PMID- 11466667
TI  - Can malnutrition in predialysis patients be prevented by dietetic intervention?
AB  - OBJECTIVE: This study aimed to discover if the documented decline in nutritional
      status in predialysis patients could be prevented by dietetic intervention.
      DESIGN: Longitudinal prospective interventional study. SETTING: General hospital
      nephrology clinic. PATIENTS: Eleven patients with progressive chronic renal
      failure not yet requiring dialysis, all with creatinine clearance below 25 mL/min
      were studied. Mean age was 63.9 +/- 14.5 years. INTERVENTION: Patients received
      nutritional counseling from a renal dietitian on at least 3 occasions over a
      period of 6 months. Following assessment, patients were advised on dietary
      changes according to individual need, aiming for adequate energy intake to
      achieve or maintain a body mass index of 20 to 25 and protein intake of 0.8 to
      1.0 g/kg/d. Dietary supplements were prescribed when necessary. OUTCOME MEASURES:
      Changes in nutritional status were assessed by Subjective Global Assessment,
      anthropometric measures (weight, triceps skinfold thickness, mid arm muscle
      circumference, and grip strength), and biochemical markers (serum albumin, serum
      transferrin, and insulin-like growth factor-1). RESULTS: None of the patients
      showed decline in Subjective Global Assessment category, and 2 of the patients
      improved. All anthropometric and biochemical measures of nutritional status were
      stable or increased over the course of the study, and mid arm muscle
      circumference increased significantly (P <.05), contrasting with published data
      showing a decline in these measures in patients not receiving dietetic
      intervention. CONCLUSION: With dietetic intervention, it may be possible to
      maintain or improve nutritional status in this group.

PMID- 11466668
TI  - Comparison of the effects of two early intervention strategies on the health
      outcomes of malnourished hemodialysis patients.
AB  - OBJECTIVE: To determine the efficacy and cost-effectiveness of providing oral
      supplementation early in the course of malnutrition for hemodialysis (HD)
      patients. DESIGN: The study design consisted of 3 groups: an experimental group,
      a control group of patients with mild hypoalbuminemia (HA) (serum albumin [SA] =
      3.5 to 3.7 g/dL), and a comparison group of patients with moderate to severe HA
      (SA = 2.5 to 3.4 g/dL). SETTING: Ten outpatient hemodialysis centers in southeast
      lower Michigan. PATIENTS: Treatment and control groups consisted of 32 HD
      patients with mild HA. Fourteen HD patients with moderate to severe HA comprised
      the comparison group. INTERVENTION: The experimental group received diet
      counseling and oral supplementation, and the control group received diet
      counseling only. The comparison group received physician-prescribed oral
      supplements and dietary counseling to permit comparison of the experimental
      treatment with current supplementation practices. MAIN OUTCOME MEASURES:
      Differences between groups in the number of patients reaching nutritional
      repletion, change in SA levels at the end of the study, and follow-up periods,
      were tested using chi-square analysis. Analysis of variance was used to compare
      group differences in treatment duration to repletion and number of
      hospitalization days. RESULTS: During the study period, significantly more
      patients reached nutritional repletion in the experimental group and control
      group (50% and 57%, respectively) than in the comparison group (7%). Overall,
      repletion occurred more quickly in the experimental group (3.2 +/- 1.7 months)
      than in the control group (3.5 +/- 1.2 months), with a larger number of patients
      in the experimental group repleted by month 2 of the study phase. During follow
      up, patients in the experimental group were far more likely to maintain
      nutritional repletion or continue to improve (61%) than patients in the control
      group (14%). Although too few patients were hospitalized to show statistical
      significance, there was a trend toward greater numbers of hospital days in more
      malnourished patients (208 days for the comparison group), followed by those with
      mild HA who did not receive oral supplements (107 days), and the experimental
      group (71 days). CONCLUSION: Although the sample size for this study was too
      small for the results to be conclusive, it appears that use of nutritional
      supplements early in the course of malnutrition may provide benefits such as,
      attaining nutritional repletion more quickly, which results in less product
      usage. It is also more likely that good nutritional status will be maintained
      after supplementation is discontinued.

PMID- 11466669
TI  - Patients' experiences of a dialysis diet and their implications for the role of
      the dietitian.
AB  - OBJECTIVE: Although developments in medical technology, pharmacology, and
      nutritional science continue to improve treatment possibilities for patients with
      renal failure, the level of compliance with medical and dietetic advice remains
      poor. Previous research on compliance with treatment of chronic illness has led
      to recommendations for an improved understanding of what is involved in living
      with chronic illness in order to tailor treatment more appropriately to
      individual needs. This qualitative study set out to examine, the experiences and
      difficulties of patients on hemodialysis who follow dietary restrictions, and to
      ascertain how the dietitian can most effectively support patients in adapting to
      dietary change. DESIGN: A semi structured interview format with thematic analysis
      was chosen. SETTING: The interviews took place in the patients' homes and lasted
      between 30 and 60 minutes. PATIENTS: Participants for the study were approached
      at Taunton and Yeovil dialysis centres in Somerset, England, and were selected
      according to the following criteria: (1) all had been on hemodialysis for at
      least 6 months, (2) all had been advised to follow dietary and/or fluid
      restrictions at one time, and (3) none had any diagnosed intellectual impairment.
      Eight subjects were recruited, 4 men and 4 women. The age range was 20 to 68
      years. INTERVENTION: Participants were asked to describe in depth their
      experiences of renal failure and of a renal diet. They were asked what had helped
      them cope with the difficulties they had faced and how they saw the role of the
      dietitian. OUTCOME MEASUREMENT: The interviews were recorded, transcribed, and
      coded according to the following categories: (1) Difficulties experienced by
      participants. (2) What helped them cope with these difficulties. (3) How the
      dietitian can help support the coping process. RESULTS: Findings showed a variety
      of physical, social, and psychological difficulties that can result from the
      onset of illness, commencement of dialysis, and the imposition of dietary
      restrictions. A loss of autonomy was an underlying theme. Greater understanding,
      hope, support from others, individual activity, and personal responsibility on
      the part of patients helped them to cope more positively with the changes in
      life. CONCLUSION: Recommendations from this research include ways by which the
      dietitian can encourage greater autonomy when advising patients, and how they can
      give information in a positive, sensitive, and supportive way.

PMID- 11466671
TI  - Dose-escalated cyclophosphamide, doxorubicin, vincristine, prednisone, and
      etoposide (CHOPE) chemotherapy for patients with diffuse lymphoma: Cancer and
      Leukemia Group B studies 8852 and 8854.
AB  - BACKGROUND: To address the feasibility and outcome of moderate dose
      intensification with granulocyte-colony stimulating factor (G-CSF) for patients
      with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B
      (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and
      etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone,
      etoposide (CHOPE) regimen. METHODS: Eligibility criteria included histologically
      documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or
      immunoblastic lymphoma, Stage III--IV or bulky Stage II disease, and an ECOG
      performance status of 0--1. CALGB 8852, a group-wide study, accrued 227 patients:
      120 patients in the pilot study to determine the maximum tolerated dose (MTD)
      without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF.
      CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and
      determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both
      studies was defined as the dose at which 50% of patients had 1) Grade 4
      neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3--4
      hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis),
      or 3) were prevented from receiving 100% of drug on Day 22. RESULTS: The MTD of
      CHOPE without G-CSF was cyclophosphamide 1000 mg/m(2) on Day 1 and etoposide 100
      mg/m(2) on Days 1--3 with doxorubicin 50 mg/m(2) on Day 1, vincristine 1.4
      mg/m(2) (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1--5. With the
      addition of G-CSF at 200 microg/m(2) on Days 5--19, the MTD was cyclophosphamide
      1500 mg/m(2) and etoposide 160 mg/m(2) on Days 1-3 with standard doses of
      doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200
      microg/m(2) to 400 microg/m(2) did not allow for further dose escalation. The
      primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on
      CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS)
      rates for eligible patients on CALGB 8852 were 31% (95% confidence interval
      [95%CI], 23--39) and 48% (95%CI, 40--57), respectively. The 5-year FFS and OS
      rates for eligible patients on CALGB 8854 were 34% (95%CI, 17--52) and 51%
      (95%CI, 33--70), respectively. CONCLUSIONS: Moderate dose escalation with G-CSF
      is feasible. However, response and survival rates of patients who receive dose
      escalated CHOPE, even with the addition of G-CSF, appear similar to the rates
      reported with standard-dose CHOP.

PMID- 11466672
TI  - Expert review of the diagnosis and histologic classification of Hodgkin disease
      in a population-based cancer registry: interobserver reliability and impact on
      incidence and survival rates.
AB  - BACKGROUND: The reliability of Hodgkin disease (HD) diagnosis and histologic
      classification is an ongoing concern but has not been evaluated in a population
      based case series in 20 years. Yet, diagnostic error in cancer registry data used
      in surveying HD occurrence may produce statistics that misrepresent incidence,
      mortality, or survival. METHODS: Uniform pathology review was attempted for all
      395 women ages 19--79 years with incident HD reported to a population-based
      cancer registry in 1988--94. Agreement between original registry and review
      diagnoses was measured with positive predictive values and kappa statistics.
      Incidence rates and survival probabilities were computed based on registry and
      review diagnoses. RESULTS: Registry and review diagnosis agreed for 245 of the
      362 reviewed cases. Positive predictive values varied by histologic subtype
      (nodular sclerosis, 95%; lymphocyte predominance, 69%; mixed cellularity, 58%;
      lymphocyte depletion, 0%; not otherwise specified, 40%), but agreement was good
      overall (kappa, 0.66, 95% confidence interval, 0.56--0.76). Eleven patients were
      determined not to have HD; all were older than age 44 years. Hodgkin disease
      incidence rates differed for original and review diagnoses only in older women,
      for whom registry rates slightly overestimated incidence. Five-year survival
      rates did not differ for registry and review data overall or by age group.
      CONCLUSIONS: For most adult women patients, the diagnosis of HD was confirmed on
      review, reflecting the very good agreement between registry and review diagnoses
      for nodular sclerosis, the most common subtype. Thus, cancer registry statistics
      for this time period can provide accurate estimates of disease patterns for HD
      overall and for the nodular sclerosis variant. For other histologic subtypes,
      rates may be unreliable, and HD occurrence overall may be less dependable in
      populations with larger proportions of these subtypes.

PMID- 11466673
TI  - The development of breast carcinoma in women with thyroid carcinoma.
AB  - BACKGROUND: Breast carcinoma and thyroid carcinoma are two malignancies that
      occur most commonly in women. An association between the incidence rates of
      thyroid and breast carcinoma in women after a diagnosis of the other malignancy
      has been suggested in a retrospective analysis of a single institution's tumor
      registry. In that study, an increased incidence of breast carcinoma in
      premenopausal women previously treated for thyroid carcinoma was observed.
      METHODS: The purpose of this study was to investigate further this relation
      utilizing a large database, the National Cancer Institute's Surveillance,
      Epidemiology and End Results (SEER) database. The SEER database is maintained by
      the National Cancer Institute, and it represents 11 population-based cancer
      registries covering approximately 14% of the United States population. The study
      was a population-based retrospective cohort analysis using external comparisons.
      From 1973 to 1994, 365 women in the SEER database were identified as having both
      thyroid and breast carcinomas. The SEER database from 1973 to 1994 was utilized
      to calculate age specific and calendar year specific incidence rates for each
      year for thyroid and breast carcinomas. The expected number of second cancers for
      each age group, calendar year, and follow-up period were determined by
      multiplying these incidence rates by the age specific and calendar year specific
      number of person-years at risk. The risk ratio (RR) was calculated by dividing
      the observed by the expected number of second cancers. Statistical significance
      was determined by the Poisson test. RESULTS: A total of 1,333,115 person-years
      were available for analysis. One hundred thirteen thyroid carcinoma cases were
      diagnosed after breast carcinoma cases (RR, 0.99; P = 0.576). Two hundred fifty
      two breast carcinoma cases were diagnosed after thyroid carcinoma cases (RR,
      1.18; P = 0.007). Premenopausal women (age 20-49 years) with an index thyroid
      carcinoma have a significantly increased risk of developing subsequent breast
      carcinoma (RR, 1.42; P = 0.001). Black premenopausal women with an index thyroid
      carcinoma do not have an increased risk of developing breast carcinoma, but the
      statistical power is lower due to low numbers. No women with index breast
      carcinoma have an increased risk of developing thyroid carcinoma. CONCLUSIONS:
      Women with a history of thyroid carcinoma have a greater than expected risk of
      developing breast carcinoma. This risk is most pronounced in premenopausal white
      women. The implications of this observation with respect to breast carcinoma
      screening guidelines and thyroid carcinoma treatment guidelines deserve further
      investigation.

PMID- 11466674
TI  - Prediction of chemotherapeutic response by Technetium 99m--MIBI scintigraphy in
      breast carcinoma patients.
AB  - BACKGROUND: Significance of Technetium 99m ((99m)Tc)-MIBI scintigraphy in the
      prediction of response to anthracylines and taxanes (both are substrates for P
      glycoprotein [P-gp]) as well as relation between (99m)Tc-MIBI uptake and P-gp or
      MDR1 mRNA expression in tumors were studied in patients with breast carcinoma.
      METHODS: Forty-six female patients with locally advanced (n = 15) or metastatic
      (n = 31) breast carcinoma were recruited in this study. Before chemotherapy
      (epirubicin and cyclophosphamide [n = 20] or decetaxel [n = 26]), (99m)Tc-MIBI
      scintigraphy was performed to obtain the T/N (tumor to normal tissue) ratios of
      (99m)Tc-MIBI uptake at 10 minutes (T/N[e]) and at 180 minutes (T/N[d]) after the
      (99m)Tc-MIBI injection. Expression of MDR1 mRNA and P-gp in tumors (n = 32) were
      determined by a quantitative real-time polymerase chain reaction and
      immunohistochemistry, respectively. RESULTS: Clinical significance of T/N(e) and
      T/N(d) ratios in the prediction of chemotherapeutic response was evaluated using
      the arbitrary cutoff values of 3.0 for T/N(e) ratios and 2.0 for T/N(d) ratios.
      Positive predictive value, negative predictive value, and diagnostic accuracy of
      T/N(d) ratios (81.0%, 96.0%, and 89.1%, respectively) were higher, although
      statistically not significant, than those of T/N(e) ratios (73.3%, 77.4%, and
      76.1%, respectively), and these values were not affected by type of chemotherapy.
      MDR1 mRNA levels were not significantly different between the lesions with high
      (> or = 2.0) and low (< 2.0) T/N(d) ratios, but P-gp expression was significantly
      (P < 0.01) higher in the lesions with low T/N(d) ratios than in those with high
      T/N(d) ratios. CONCLUSIONS: T/N(d) ratios determined by (99m)Tc-MIBI scintigraphy
      are useful in the prediction of response to chemotherapy with epirubicin and
      cyclophosphamide or docetaxel as well as in the in vivo evaluation of P-gp
      expression status in tumors in patients with locally advanced or recurrent breast
      carcinoma.

PMID- 11466675
TI  - Investigation of an interaction of alcohol intake and family history on breast
      cancer risk in the Minnesota Breast Cancer Family Study.
AB  - BACKGROUND: One explanation for the variability in results in studies of alcohol
      consumption and breast cancer could be the presence of effect modifiers, such as
      genetic susceptibility. The authors examined the interaction of alcohol and
      family history of breast cancer on breast cancer risk in a population-based
      family study of 426 multigenerational breast cancer families. The authors
      evaluated whether alcohol use was a stronger risk factor for breast cancer among
      sisters, daughters, nieces, and granddaughters of breast cancer probands than
      among women who married into these families. METHODS: Analyses were performed on
      surrogate and self-reported data combined and on self-reported data alone. To
      evaluate the interaction of alcohol and breast cancer risk among women with a
      family history of breast cancer, the authors performed analyses on all 426
      families and on a subset of 132 families that had 3 or more breast and/or ovarian
      cancers in their family. RESULTS: A total of 9032 blood relatives and marry-ins
      and 558 breast cancer cases were available for analysis. In the entire 426
      families, there was a suggestion of an interaction of relationship to the proband
      and frequency of alcohol consumption on breast cancer risk (P(interaction) =
      0.14) for surrogate and self-reported information combined. Among first-degree
      relatives of the proband, daily drinkers had a significantly increased risk of
      breast cancer compared with never drinkers (RR = 2.45 [1.20, 5.02]), but this
      increase was less evident among second-degree relatives who reported daily
      alcohol intake (RR = 1.27 [0.73, 2.22]) and was not evident in marry-ins who
      reported daily use of alcohol (RR = 0.90 [0.42, 1.90]). The findings based on the
      subset of 132 high-risk families with 3 or more breast and/or ovarian cancers
      were similar to findings based on all 426 families (P(interaction) = 0.07). An
      interaction of family history with alcohol use was also suggested when the
      analyses were restricted to self-respondents, although the interaction test P
      value was no longer of borderline significance. CONCLUSION: An increased risk of
      breast cancer due to an increased frequency of alcohol consumption may be limited
      to women with a family history of breast cancer.

PMID- 11466677
TI  - Surgical treatment for skeletal breast cancer metastases: a population-based
      study of 641 patients.
AB  - BACKGROUND: The objective of this article was to assess the occurrence of
      symptomatic bone metastases in a defined population of patients with breast
      carcinoma and to characterize the clinical outcome with reference to surgical
      treatment for pathologic fracture or neurologic deficit. METHODS: The authors
      identified all patients in the Stockholm Breast Cancer Database (population base
      1.8 million) with a diagnosis of bone metastases during 1989--1994. These cases
      were linked with the Stockholm County Council Hospital Discharge Diagnosis
      Registry that includes information on in-patient care and discharge diagnoses.
      This enabled us to identify patients who had undergone surgical treatment for
      their bony metastases at any of the six departments of orthopedics in the region,
      or who had been treated at the one department of neurosurgery. RESULTS: Six
      hundred forty-one patients with breast carcinoma presented with symptomatic
      skeletal metastasis during 1989--1994, and 107 (17%) were operated on. Metastases
      were located in long bones (77), spine (14), and pelvis (6). The median survival
      postoperatively was 6 months. The total reoperation rate was 0.12. Hip screws and
      glide-screw plates were associated more often with failure as was location in the
      distal femur. Pain decreased postoperatively in 77% of the patients, and function
      improved in 65%. CONCLUSIONS: One in 10 patients with breast carcinoma developed
      symptomatic bone metastases, and one-fifth of these patients required surgery for
      pathologic fracture or neurologic deficit. There was a high failure rate in those
      hospitals in which few patients were operated on.

PMID- 11466676
TI  - Long term outcome of small size invasive breast carcinomas independent from
      angiogenesis in a series of 685 cases.
AB  - BACKGROUND: To document the role of neoangiogenesis in the progression of breast
      carcinomas, intratumoral vascular density (ITVD) was assessed and compared to
      pathologic data and disease outcome in a series of 685 cases. METHODS: Patients
      were registered between 1981 and 1988 at the Curie Institute. Tumors corresponded
      to small size (< or = 30 mm) invasive carcinomas, 71% of which were axillary
      lymph node-negative. In all cases, conservative surgery was the initial
      therapeutic procedure. The median follow-up was 10.8 years. ITVD was
      retrospectively determined as the number of immunostained (anti-F8RA/vWF
      antibody) vessels in an area of 1.2 mm(2). The prognostic value of ITVD regarding
      overall survival, locoregional recurrence-free, and metastasis-free intervals was
      assessed in uni- and multivariate analyses. RESULTS: Microvessel count ranged
      from 5--245 per 1.2 mm(2) field. The median value was 62, and the mean was 67.
      The median was chosen as a cut point for statistical analysis. ITVD was found to
      be inversely linked to tumor size (P < or = 0.0001) and histologic grade (P =
      0.005), and directly linked to vascular invasion (P = 0.02). In uni- and
      multivariate analysis, no significant link was found between ITVD and disease
      outcome, even after adjustment on histologic grade and tumor size. CONCLUSIONS:
      ITVD was inversely correlated to tumor size and histologic grade in our series of
      small-size breast carcinomas. No significant link between ITVD and disease
      outcome was observed. Evaluation of the role of angiogenesis in tumor progression
      should be based on the discriminative assessment of mature and/or activated
      vessels.

PMID- 11466678
TI  - Radioisotope-guided surgery in patients with pheochromocytoma and recurrent
      medullary thyroid carcinoma: a comparison of preoperative and intraoperative
      tumor localization with histopathologic findings.
AB  - BACKGROUND: The objective of this study was to appraise the detection of
      metastases of medullary thyroid carcinoma (MTC) and pheochromocytoma using
      radioguided surgery (RGS) and to compare the results with external imaging
      modalities, surgical palpation, and histopathologic findings. METHODS: Twenty
      five patients with recurrent MTC underwent preoperative scintigraphic imaging
      with 500 megabecquerels (MBq) of technetium 99m(V)-dimercaptosuccinic acid
      [(99m)Tc(V)-DMSA] and 222 MBq of indium 111 ((111)In)-pentetreotide. The
      radiopharmaceutical that showed the greatest preoperative tumor uptake was
      selected for intraoperative RGS. Surgery was performed 24 hours after the
      administration of (111)In-pentetreotide or 4 hours after the injection of
      (99m)Tc(V)-DMSA. Furthermore, three male patients underwent surgery who suffered
      from recurrent pheochromocytoma (injection of 180 MBq iodine 123-labeled
      metaiodobenzylguanidine [(123)I-MIBG] 4--5 hours before surgery). RESULTS:
      Overall, lesion detection sensitivities in patients with MTC for computed
      tomography, (111)In-pentetreotide, and (99m)Tc(V)-DMSA were 32%, 34%, and 65%,
      respectively. Surgical palpation identified lymph node metastases of recurrent
      MTC with a sensitivity of 65%, whereas RGS localized 64 malignant lesions
      (sensitivity, 97%). Altogether, 71 lesions could be excised, 5 of which were
      adjudged false positive with respect to MTC metastases. Both surgical palpation
      and RGS localized all paravertebral subdiaphragmatic lesions (size > or = 2 cm)
      of recurrent pheochromocytoma seen in the preoperative MIBG scan. CONCLUSIONS:
      RGS was capable of localizing more and smaller metastases of MTC compared with
      conventional imaging modalities and surgical palpation. However, the relatively
      high radioligand accumulation in the kidneys ((111)In-pentetreotide) and the
      dense hepatic and biliary signals using MIBG limited their use for intraoperative
      detection of tumors in the area of the adrenal gland.

PMID- 11466679
TI  - Expression of survivin is correlated with cancer cell apoptosis and is involved
      in the development of human pancreatic duct cell tumors.
AB  - BACKGROUND: Survivin is a new member of the inhibitor of apoptosis family of
      antiapoptotic proteins. This protein was expressed selectively in all the most
      common human carcinomas but not in normal adult tissues. To our knowledge, the
      relation between survivin expression and apoptosis or tumorigenesis has not yet
      been studied in pancreatic neoplasms. METHODS: The authors investigated the
      expression of survivin in 4 pancreatic carcinoma cell lines and 56 human
      pancreatic tissues (5 cases of normal, 12 cases of chronic pancreatitis [CP], 26
      cases of pancreatic duct cell adenocarcinoma [PDC], 16 lesions of 13 intraductal
      papillary-mucinous tumor [IPMT] by immunohistochemistry, immunoblotting, and
      reverse transcription-polymerase chain reaction (RT-PCR) to examine the
      association of its expression with tumor apoptosis and/or tumorigenesis. RESULTS:
      Survivin expression was found in the tumor cells but not in the nonneoplastic
      pancreatic tissues (normal and CP tissues). Survivin expression was observed in
      20 of 26 cases of PDC (76.9%) and in 9 of 16 IPMT lesions that ranged from
      adenoma to invasive (56.3%) by immunohistochemistry. Survivin was more frequently
      expressed in malignant tumors than in benign tumors (P = 0.0089). In PDC, high
      levels of survivin expression were associated significantly with a reduction in
      the apoptotic index of the tumor cells (0.445% +/- 0.150% vs. 0.961% +/- 0.378%;
      P < 0.0001). CONCLUSIONS: These data suggest that the expression of survivin may
      be upregulated during an early step of tumorigenesis and during the development
      of cancer by reducing the cancer cell apoptosis.

PMID- 11466680
TI  - A three-step strategy of induction chemotherapy then chemoradiation followed by
      surgery in patients with potentially resectable carcinoma of the esophagus or
      gastroesophageal junction.
AB  - BACKGROUND: Patients with locoregional carcinoma of the esophagus or
      gastroesophageal junction have a poor survival rate after surgery. Preoperative
      chemotherapy or chemoradiotherapy has not improved the outcome for these
      patients. Our study was designed to assess the feasibility of preoperative
      induction combination chemotherapy in addition to chemoradiotherapy to improve
      the curative resection rate, local control, and survival. PATIENTS AND METHODS
      Patients having histologic proof of localized carcinoma (either squamous cell
      carcinoma or adenocarcinoma) of the esophagus or gastroesophageal junction
      underwent full classification including endoscopic ultrasonography (EUS).
      Patients first received up to two courses of induction chemotherapy consisting of
      5-fluorouracil at 750 mg/m(2)/day as continuous infusion on Days 1--5, cisplatin
      at 15 mg/m(2)/day as an intravenous bolus on Days 1--5, and paclitaxel at 200
      mg/m(2) as a 24-hour intravenous infusion on Day 1. The second course was
      repeated on Day 29. This was followed by radiotherapy (45 grays in 25 fractions)
      and concurrent admission of 5-fluorouracil (300 mg/m(2)/day as a continuous
      infusion 5 days/week) and cisplatin (20 mg/m(2) on Days 1--5 of radiotherapy).
      After chemoradiotherapy, patients underwent surgery. The feasibility of this
      approach, curative resection rates, patient survival, and patterns of failure
      were assessed. RESULTS: Thirty-seven of 38 patients enrolled were evaluable for
      toxicity and survival. Adenocarcinoma and distal esophageal location of carcinoma
      were observed frequently. Thirty-five (95%) of the 37 patients underwent surgery,
      all of whom had an R0 (curative) resection. A pathologic complete response was
      noted in 11 (30%) of the 37 total patients. In addition, 5 patients (14%) had
      only microscopic carcinoma. According to EUS classification, 31 (89%) of the 35
      patients who underwent surgery had a T3 carcinoma whereas according to pathologic
      classification only 3 (9%) had a T3 carcinoma (P </= 0.01). Similarly, according
      to EUS classification, 23 patients (66%) had an N1 carcinoma, whereas according
      to pathologic classification only 7 patients (20%) had an N1 carcinoma (P < or =
      0.01). At a median follow-up of 20 months (minimum follow-up, 13+ months; maximum
      follow-up, 36+ months), the median survival duration for the 37 patients had not
      yet been reached. In addition, there were two deaths related to surgery.
      CONCLUSIONS: These data show that the three-step strategy of preoperative
      paclitaxel-based induction chemotherapy then chemoradiotherapy followed by
      surgery is feasible and appears quite active in patients having locoregional
      carcinoma of the esophagus or gastroesophageal junction. Future investigations
      should focus on substituting cisplatin with less toxic agents and including more
      systemic therapy with newer classes of agents.

PMID- 11466681
TI  - Significance of serum soluble Fas ligand in patients with bladder carcinoma.
AB  - BACKGROUND: The interaction of Fas and Fas ligand (FasL) plays an important role
      in cytotoxic T-lymphocyte-mediated and natural killer cell-mediated apoptosis
      against tumor cells. Circulating soluble FasL (sFasL) has been suggested to
      provide protection from Fas-mediated apoptosis. The current study examined this
      possibility in patients with bladder carcinoma. METHODS: The levels of sFasL in
      the serum of 163 patients with bladder carcinoma were determined using an enzyme
      linked immunoadsorbent assay. Antiautologous tumor cytotoxic activity was
      assessed by the 12-hour chromium isotope ((51)Cr) release assay. RESULTS: The
      mean serum level of sFasL in patients with bladder carcinoma was 2.5-fold higher
      than that in healthy donors. The level of serum sFasL in patients with muscle
      invasive bladder carcinoma was 2.5-fold higher than that in patients with
      superficial bladder carcinoma. In addition, serum sFasL levels in patients with
      T1 and Tis bladder carcinoma was 2-fold and 2.7-fold higher, respectively, than
      levels in patients with Ta bladder carcinoma. The serum level of patients with
      sFasL in Grade 3 bladder carcinoma were 2.4-fold and 1.7-fold higher than that in
      patients with Grade 1 and Grade 2 bladder carcinoma, respectively. Patients with
      Ta bladder carcinoma with a low level of serum sFasL (less than the median value)
      had a longer postoperative tumor-free interval than patients with a high sFasL
      level (greater than the median value) in the 5-year follow-up. There was an
      apparent inverse correlation between the level of serum sFasL and antiautologous
      tumor cytotoxic activity. CONCLUSIONS: The results of the current study
      demonstrated that the level of serum sFasL is correlated with both disease
      progression and increase in the tumor grade, and that an elevated serum sFasL
      level predicted early recurrence in patients with Ta bladder carcinoma. These
      findings suggest that elevated serum sFasL levels might be associated with a
      greater risk of disease progression and recurrence in patients with bladder
      carcinoma.

PMID- 11466682
TI  - DNA aneuploidy and high proliferative activity but not K-ras-2 mutations as
      independent predictors of clinical outcome in operable gastric carcinoma: results
      of a 5-year Gruppo Oncologico dell'Italia Meridonale (GDIM) prospective study.
AB  - BACKGROUND: The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras
      2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim
      of this study was to clarify the association between biomolecular variables,
      tumor characteristics, and clinical outcome in GC patients. METHODS: Resected
      specimens from a consecutive series of 69 patients with GC who underwent
      potentially curative surgery were studied prospectively. DNA ploidy and SPF were
      assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2
      mutations were detected by polymerase chain reaction followed by single-strand
      conformation polymorphism. All the patients involved in this study were followed
      up for a mean of 95 months. RESULTS: DNA aneuploidy was present in 72% of the
      cases (50 of 69), whereas 10% of these (5 out of 50) showed multiclonality.
      Mutations of K-ras-2 were detected in 8% of the tumors (5 of 63). Both DNA ploidy
      and SPF were associated with TNM stage (American Joint Committee on Cancer [AJCC]
      staging system) and node status. Moreover, DNA aneuploidy was significantly
      related to high SPF. K-ras-2 mutations were not associated with clinicopathologic
      variables or flow cytometric indicators. At univariate analysis, advanced TNM
      stage, node involvement, diffuse histotype, depth of invasion, DNA aneuploidy,
      and high SPF proved to be significantly related to quicker tumor relapse and to
      shorter overall patient survival. With multivariate analysis, DNA aneuploidy,
      high SPF, and depth of invasion were related to risk of tumor relapse and patient
      death, whereas diffuse histotype was independently related to patient risk of
      tumor relapse. CONCLUSIONS: DNA ploidy and SPF, when associated with
      clinicopathologic staging, might be useful for the identification of GC patients
      who have different risks for death or relapse of disease.

PMID- 11466683
TI  - A prospective study of factors predicting clinically occult spinal cord
      compression in patients with metastatic prostate carcinoma.
AB  - BACKGROUND: The objective of this study was to identify clinical parameters that
      predict occult subarachnoid space or spinal cord (SAS/SC) compression, as
      determined by magnetic resonance imaging (MRI), in patients with metastatic
      prostate carcinoma. METHODS: A prospective study was performed in which 68
      patients with bone metastases from prostate carcinoma and a normal neurologic
      examination underwent MRI of the entire spine after documentation of clinical, X
      ray, and bone scan parameters potentially predictive of occult SAS/SC
      compression. RESULTS: Occult SAS/SC compression was diagnosed in 22 patients
      (32%) using MRI. Nine patients (13%) had compressions at two discontinuous spinal
      levels. Extensive disease on bone scan, the duration of continuous hormonal
      therapy prior to study entry, and hemoglobin concentration were found to predict
      SAS/SC compression by univariate analysis. The extent of disease on bone scan and
      the duration of continuous hormonal therapy were independent predictors of SAS/SC
      compression by multivariate analysis (P = 0.02 and P = 0.04, respectively). The
      risk of occult SAS/SC compression increased from 32% to 44% in patients with a
      bone scan that showed > 20 metastases as the duration on hormones increased from
      0 to 24 months. The risk in patients with fewer metastases increased from 11% to
      17% over the same interval. The presence or absence of back pain was not
      predictive of SAS/SC compression. CONCLUSIONS: Patients who are at high risk for
      occult SAS/SC compression can be identified using clinical parameters and readily
      available diagnostic tests. These high-risk patients should undergo MRI screening
      with the aim of diagnosing and treating spinal cord compression before the
      development of neurologic deficits that may be irreversible.

PMID- 11466684
TI  - Prognostic significance of histologic grading in patients with prostate carcinoma
      who are assessed by the Gleason and World Health Organization grading systems in
      needle biopsies obtained prior to radiotherapy.
AB  - BACKGROUND: The current study was conducted to evaluate and compare the impact of
      two major histologic grading systems on failure-free survival in patients with
      prostate carcinoma who are treated with definitive radiation. METHODS: Eligible
      patients for the current study had localized adenocarcinoma of the prostate (T1
      4pN0M0, T3/4: 67%, median observation time: 69 months) and were treated with
      intent-to-cure external radiotherapy between 1989 and 1995. The specimens from
      178 patients, obtained by needle biopsies, were reviewed simultaneously by two
      pathologists assigning World Health Organization (WHO) and Gleason grades. Three
      tiered Gleason grouping distributed patients into three groups (those with a
      score < 7, those with a score of 7, and those with a score of 8--10), whereas two
      tiered Gleason categorization distributed patients into two groups (those with a
      Gleason score of 7A, major 3 + minor 4 patients were added to the group of
      patients with a Gleason score < 7 and patients with a Gleason score of 7B, major
      4 + minor 3 were added to the group of patients with a Gleason score of 8--10).
      Univariate and multivariate analyses were performed. A P value < 0.05 was
      considered to be statistically significant. RESULTS: Three-tiered Gleason
      grouping resulted in a relatively even distribution of the patients (44 patients
      had a Gleason score < 7, 58 patients had a Gleason score of 7, and 76 patients
      had a Gleason score of 8--10) whereas 130 patients were determined to have Grade
      2 tumors based on WHO criteria. Separating those patients with a Gleason score of
      7 (score 3+4 vs. score 4+3) led to the two-tiered Gleason grouping (88 patients
      in the favorable group and 90 patients in the unfavorable group). The two-tiered
      Gleason grouping displayed differences with regard to failure-free survival with
      the lowest P values for all patients and separately for T1/2 versus T3/4 tumors.
      Together with T category and pretreatment prostate specific antigen, WHO grading,
      three-tiered Gleason grouping, and two-tiered Gleason grouping resulted in
      independent parameters in the Cox regression model. The proportional variance
      estimate confirmed the superior discrimination for survival of two-tiered Gleason
      grouping. CONCLUSIONS: The equal allocation of patients to subgroups based on the
      Gleason system helps the clinician to overcome the dilemma of overrepresentation
      of Grade 2 patients as occurs with WHO grading. The Gleason grading system and,
      most likely, the two-tiered Gleason grouping appear to result in better
      prognostic separation of patients referred to radiotherapy for relatively
      advanced primary tumors. Therefore the authors recommend the routine use of
      Gleason grading for these patients.

PMID- 11466685
TI  - Infertility treatment after conservative management of borderline ovarian tumors.
AB  - BACKGROUND: Young patients with ovarian tumors of low malignant potential usually
      undergo conservative surgery because of the excellent prognosis of these tumors.
      Patients wishing to conceive after diagnosis occasionally require ovulation
      induction, but data regarding the safety of assisted reproductive technologies in
      this situation remains anecdotal. The current study analyzes the outcome of a
      group of patients who received infertility treatment after the conservative
      management of borderline ovarian tumors. METHODS: The clinical and pathologic
      records of 104 patients with a borderline tumor of the ovary who were treated and
      followed over a 20-year period (1979--1999) were reviewed. Forty-three patients
      who underwent conservative management were the subjects of the current study.
      RESULTS: Follow-up was available for 95% of the patients, giving a total of 270
      women-years of follow-up. Nine of the 43 patients developed a local recurrence, 8
      of which occurred in patients with serous tumors. Five of these 9 patients
      underwent cystectomy only at the time of recurrence, and all were without
      evidence of disease at a mean follow-up of 75 months (range, 25--93 months).
      Nineteen patients delivered a total of 25 healthy children after diagnosis of a
      borderline ovarian tumor; 7 of these patients were treated with in vitro
      fertilization (IVF) after diagnosis. Four of these patients developed a
      recurrence, two patients before the IVF treatment and two patients after the IVF
      treatment. The latter two patients were without evidence of disease at the time
      of last follow-up (15 months and 26 months, respectively, after the recurrence).
      CONCLUSIONS: The results of the current study suggest that ovulation induction
      may be considered after the diagnosis of a borderline ovarian tumor. Recurrences
      were observed in two of seven patients, all of which remained histologically
      borderline.

PMID- 11466686
TI  - A phase II study of combined oral uracil and ftorafur with leucovorin for
      patients with squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The objective of this Phase II study was to define the response rate,
      safety profile, and toxicity of oral uracil and ftorafur (UFT) with leucovorin
      (UFT/LV) as a palliative treatment for patients with squamous cell carcinoma of
      the head and neck (SCCHN). METHODS: Patients with metastatic or recurrent SCCHN
      with an Eastern Cooperative Oncology Group performance status < 2 and adequate
      organ function were enrolled in an institutional review board-approved trial.
      Prior induction or adjuvant chemotherapy was permitted provided 6 months had
      elapsed since the last chemotherapy. Patients were treated with UFT 300 mg/m(2)
      per day and leucovorin 90 mg per day administered in three doses daily for 28
      days followed by a 7-day break for a 35-day cycle. Planned intrapatient dose
      modifications were based on individual toxicity. Patients were removed from the
      study for progression of disease or unacceptable toxicity. RESULTS: One hundred
      six cycles of UFT/LV had been administered to 42 patients as of January 1, 2000.
      The most common toxicities, in descending order of incidence, were anemia, pain,
      fatigue, diarrhea, nausea, mucositis, and anorexia. Clinically significant
      toxicities attributable to UFT/ LV were primarily gastrointestinal. On an intent
      to-treat basis, three patients (7%) achieved a complete response, and six
      patients (14%) achieved a partial response. The overall response rate was 21%
      (95% confidence interval, 10--37%). CONCLUSIONS: UFT/LV therapy is feasible in
      this patient population and is generally well tolerated. Response rates are
      similar to the rates expected with continuous-infusion 5-fluorouracil. UFT/LV
      should be studied further both alone and in combination therapy for patients with
      SCCHN.

PMID- 11466687
TI  - Biallelic inactivation of the APC gene is associated with hepatocellular
      carcinoma in familial adenomatous polyposis coli.
AB  - BACKGROUND: Certain primary hepatic tumors have been associated with familial
      adenomatous polyposis (FAP), a condition caused by germline mutations of the
      adenomatous polyposis coli (APC) gene. However, a genetic association between FAP
      and hepatocellular carcinoma (HCC) has not been shown. This study tested the
      hypothesis that biallelic inactivation of the APC gene contributed to the
      development of HCC in a patient with FAP and a known germline mutation of the APC
      gene at codon 208, but no other risk factors for HCC. METHODS: Total RNA and
      genomic DNA were isolated from the tumor, and in vitro synthesized protein assay
      and DNA sequencing analysis were used to screen for a somatic mutation in the APC
      gene. RESULTS: A somatic one-base pair deletion at codon 568 was identified in
      the wild-type allele of the APC gene. CONCLUSIONS: To the authors' knowledge,
      this study provides the first evidence that biallelic inactivation of the APC
      gene may contribute to the development of HCC in patients with FAP.

PMID- 11466688
TI  - Liver metastasis from gallbladder carcinoma: anatomic correlation with
      cholecystic venous drainage demonstrated by helical computed tomography during
      injection of contrast medium in the cholecystic artery.
AB  - BACKGROUND: The current study evaluated whether the sites of liver metastasis
      from gallbladder carcinoma are correlated with areas of cholecystic venous
      drainage (CVD) utilizing helical computed tomography (CT) during the injection of
      contrast medium into the cholecystic artery (cholecystic artery CT). METHODS:
      Cholecystic artery CT scans were performed in 26 patients with gallbladder
      carcinoma. Liver metastases were examined retrospectively in these patients on
      CT, and the sites of liver metastasis and CVD were compared closely. The patients
      were divided into concurrent (those who had metastasis at the time of cholecystic
      artery CT), early postoperative metastasis (those who developed metastasis within
      6 months after surgery), and late postoperative metastasis (those who developed
      metastasis more than 6 months after surgery) groups. The frequency of metastasis
      related to CVD was compared between the three groups. RESULTS: A total of 32
      metastases were identified in 11 patients, 21 of which were related to CVD. Six
      patients were included in the concurrent metastasis group; 18 of 20 tumors were
      found to be related closely to CVD. There were two patients in the early
      postoperative metastasis group; all three of the tumors detected were found to be
      closely related to CVD. Three patients were subclassified as being in the late
      postoperative metastasis group; none of the nine tumors detected appeared to be
      in areas associated with CVD. CONCLUSIONS: The sites of liver metastases were
      found to be well correlated with the areas with CVD, particularly in the
      concurrent and early postoperative metastasis groups. CVD may be a useful marker
      of potential areas of liver metastasis from gallbladder carcinoma, particularly
      in patients with early stage metastasis.

PMID- 11466689
TI  - Clinical and biologic characteristics for recurring neuroblastoma at mass
      screening cases in Japan.
AB  - BACKGROUND: It is said that most cases detected by neuroblastoma mass screening
      at 6 months of age tend to have a favorable clinical course after a surgical
      resection either with or without mild chemotherapy. However, a few cases have an
      unfavorable outcome. In the current study, the authors analyzed the clinical and
      biologic characteristics for recurring neuroblastoma in mass screening cases.
      METHODS: In 245 cases detected through mass screening in the Kyushu area in
      Japan, the clinical data and biologic features (N-myc status, DNA ploidy, Shimada
      histology, neuron-specific enolase (NSE), ferritin) were investigated, whereas,
      in particular, the data for recurring cases also were analyzed. RESULTS: Of 245
      cases, 28 tumors had one or more biologically unfavorable prognostic factors, and
      6 patients experienced recurrence. Three of the six patients with recurring
      disease underwent a complete resection of the primary tumor, whereas three cases
      had undergone an incomplete resection of the tumor. Regarding the initial
      chemotherapy, three cases received mild chemotherapy, two cases received no
      chemotherapy, and one case had high-dose multidrug chemotherapy. Regarding
      biologic prognostic factors, four of six cases with recurring disease had one or
      more unfavorable factors, whereas two cases had no unfavorable factors. Regarding
      the outcome after recurrence, four cases are CR, one case has a stable residual
      tumor, and one case died of disease with N-myc amplification. CONCLUSIONS: Most
      neuroblastomas detected by mass screening at 6 months of age have biologically
      favorable factors. However, approximately 10% of the cases had one or more
      unfavorable factors and thus might have a higher risk of recurrence than the
      patients with no unfavorable factors. Conversely, some cases with recurring
      disease had no unfavorable factors; however, the reason for this is still
      unclear. A long-term follow-up for mass screening cases is important, and it also
      might be necessary to research the established biologic factors and identify
      other new prognostic factors.

PMID- 11466690
TI  - Cutaneous basal cell carcinomas: distinct host factors are associated with the
      development of tumors on the trunk and on the head and neck.
AB  - BACKGROUND: Patients with basal cell carcinoma (BCC) demonstrate marked variation
      in clinical phenotype, suggesting the presence of distinct subgroups. Patients
      with truncal lesions comprise an interesting subgroup, because, although the
      pathogenesis of these tumors is unclear, there is evidence to suggest that their
      development is mediated by different mechanisms than the mechanisms that mediate
      the development of BCC on other sites. The authors now speculate that some
      patients inherit a predisposition to truncal BCC and develop disproportionately
      more BCC on this site than other patients. METHODS: The authors studied 100
      patients who, at the time of initial presentation, had a truncal BCC lesion and
      493 patients who had a lesion on the head and neck. The 493 patients with head
      and neck lesions included 36 patients who subsequently developed a truncal BCC
      and 457 patients who do not. RESULTS: Initial presentation with a truncal tumor
      was associated with significantly more subsequent BCC lesions on this site
      compared with patients who presented initially with a head and neck lesion. The
      mean truncal tumor accrual after initial presentation in patients who presented
      with an initial truncal BCC lesion was 0.13 BCC lesions per year compared with
      0.03 BCC lesions per year in patients who presented with an initial head and neck
      lesion (P < 0.001). Patients with truncal lesions were significantly younger at
      the time of initial presentation and developed more clusters of BCC lesions (2-
      10 new tumors at any presentation) compared with patients who did not develop
      tumors on the trunk. CONCLUSIONS: These data suggest that the development of a
      truncal BCC is not random but, rather, is associated with a predisposition. In
      contrast, the accrual of nontruncal BCC lesions was similar in patients with and
      without initial truncal lesions, suggesting that different mechanisms determine
      the development of truncal BCC and nontruncal BCC.

PMID- 11466691
TI  - Prognostic factors in retroperitoneal sarcoma: a multivariate analysis of a
      series of 165 patients of the French Cancer Center Federation Sarcoma Group.
AB  - BACKGROUND: Surgery is the main prognostic factor in retroperitoneal sarcoma.
      However, despite progress, surgery alone is rarely curative, and analysis of the
      causes of failures and of other prognostic factors are warranted to ascertain
      treatment orientations. METHODS: Data of patients treated from 1.80 to 12.94 for
      primary retroperitoneal sarcoma were extracted from the French Federation of
      Cancer Centers Sarcoma Group registry. Univariate and multivariate analysis were
      performed for initial local control and for local and general outcome. One
      hundred sixty-five patients (median age, 54 years; range, 16--82 years) were
      identified. Median tumor size was 15 cm (range, 2--70 cm); 31% of tumors
      presented with neurovascular or bone involvement. Liposarcoma, leiomyosarcoma,
      and malignant fibrous histiocytoma represented 66% of the tumors. Eighty-four
      percent of the tumors were of high or intermediate grade. Twenty patients had
      initial metastases. Multimodality treatment included surgery (150 patients),
      radiotherapy (92 patients), and chemotherapy (77 patients). Complete excision was
      achieved in 94 of 145 nonmetastatic patients. Median follow-up was 47 months
      (range, 3--160 months). RESULTS: Actuarial overall 5-year survival rate (median)
      was 46% (51 months). The main prognostic factors for survival were initial
      metastases and surgery, which represented the major treatment-linked factor. High
      grade of tumors affected local recurrence, metastatic recurrence, and survival.
      Adjuvant radiotherapy was significantly associated with reduced local recurrence.
      Various evolutive patterns were observed with histologic subtypes. CONCLUSIONS:
      Aggressive surgery remains mandatory in retroperitoneal sarcoma, but a randomized
      trial is needed to evaluate the place of radiotherapy for local control.

PMID- 11466692
TI  - Soluble human leukocyte antigen--G serum level is elevated in melanoma patients
      and is further increased by interferon-alpha immunotherapy.
AB  - BACKGROUND: The nonclassic human major histocompatibility complex class I
      antigens human leukocyte antigen (HLA)--G are proposed to protect tumor cells
      from natural killer cell lysis. In the current study, the authors measured
      soluble HLA-G molecules (sHLA-G) in serum from patients with malignant melanoma.
      METHODS: Soluble HLA-G was determined in serum samples of 190 melanoma patients
      with various stages of disease, with or without current therapy including
      interferon (IFN)-alpha and different cytostatics in comparison to 126 healthy
      controls by using a two-step enzyme-linked immunoadsorbent assay. RESULTS: Serum
      sHLA-G was significantly (P < 0.0005) elevated in melanoma patients (mean +/-
      standard error of the mean [SEM] = 41.95 +/- 2.15 ng/mL) compared with healthy
      controls (mean +/- SEM = 22.92 +/- 1.51 ng/mL). Univariate analysis revealed a
      correlation of sHLA-G serum level with advanced stages of disease (P < 0.001) and
      tumor load (P < 0.05). Patients undergoing immunotherapy with IFN-alpha (n = 31)
      showed an increased serum sHLA-G (mean +/- SEM = 62.05 +/- 7.58 ng/mL; P <
      0.0005), whereas other treatment regimens (n = 24) did not influence sHLA-G serum
      concentrations. Multivariate analysis revealed treatment with IFN-alpha as the
      only impact factor for elevated serum sHLA-G, lacking any correlation with stage
      of disease or tumor burden. Furthermore, IFN-alpha was found to upregulate HLA-G
      cell surface expression on circulating monocytes. sHLA-G serum level was not
      associated with recurrence free or overall survival. CONCLUSIONS: This study
      shows increased sHLA-G serum concentrations in melanoma patients and additional
      enhancement upon treatment with IFN-alpha. The level of serum sHLA-G, however,
      had no negative impact on patients' prognosis.

PMID- 11466693
TI  - Gains of chromosome 22 by fluorescence in situ hybridization in the context of an
      hyperdiploid karyotype are associated with aggressive clinical features in
      meningioma patients.
AB  - BACKGROUND: Meningiomas usually are considered to be benign tumors; however, 10
      20% of cases recur. Few disease characteristics have proved to have prognostic
      impact for predicting disease free survival. The objective of the current study
      was to explore the prognostic value of numeric abnormalities of chromosome 22 for
      meningioma patients. METHODS: In this study, the authors prospectively analyzed
      the incidence of numeric chromosome abnormalities of chromosome 22 by interphase
      fluorescence in situ hybridization, using a specific probe for the bcr gene
      located in chromosome 22q11.2, on a total of 88 consecutive meningioma patients.
      The authors also analyzed its correlation with both the clinicobiologic
      characteristics at presentation and the patient's outcome. RESULTS: The authors'
      results show that monosomy 22 was present in 49% of the cases and that this
      numeric chromosomal abnormality is not associated with other prognostic features
      of the disease. In contrast, gains (trisomy/tetrasomy) of chromosome 22 were
      detected in 8 (9%) cases who simultaneously showed gains for other chromosomes
      and represent an adverse prognostic factor regarding disease free survival (P =
      0.001); in addition, trisomy/tetrasomy 22 was more frequently related to younger
      patients (P = 0.001), aggressive histopathologic features (P < 0.000), a greater
      incidence of DNA aneuploidy (P =0.006), and a higher proportion of S-phase tumor
      cells (P = 0.02). CONCLUSIONS: In summary, the authors conclude that loss of a
      copy of chromosome 22 is a frequent finding in meningioma tumors, but it does not
      affect the clinical outcome of these patients. In contrast, gains
      (trisomy/tetrasomy) of chromosome 22, in the context of an hyperdiploid
      karyotype, although much less frequent, are associated with a more aggressive
      disease course.

PMID- 11466694
TI  - Association of p53 gene mutations with sensitivity to TZT-1027 in patients with
      clinical lung and renal carcinoma.
AB  - BACKGROUND: It has been revealed that chemotherapy using DNA-damaging agents and
      radiotherapy were influenced by the p53 status of tumors; however, p53 status did
      not influence chemotherapy using antimicrotubule agents. To elucidate whether a
      novel antimicrotubule agent, TZT-1027, is influenced by the p53 status of tumors,
      the authors investigated the sensitivities of specimens obtained from patients
      with nonsmall cell lung carcinoma (NSCLC) and renal cell carcinoma (RCC) to
      various anticancer agents, including TZT-1027, and the status of the p53 gene in
      those specimens. METHODS: Twenty-nine NSCLC specimens and 22 RCC specimens were
      analyzed for their sensitivity to various anticancer agents and their p53 status.
      Sensitivities of the specimens to nine anticancer agents were determined by flow
      cytometric analysis. To determine p53 status, polymerase chain reaction
      amplification with primers for exons 5--9 was conducted, and the products were
      subjected to single-strand conformation polymorphism analysis. RESULTS: In the
      NSCLC specimens, anticancer agents, including TZT-1027, showed strong antitumor
      activity against 50--75% of specimens with the wild type p53 gene. TZT-1027
      showed strong antitumor activity against 40% of specimens with the mutant type
      p53 gene, whereas DNA-damaging agents showed such activity only in 16--28% of
      specimens. In RCC specimens, TZT-1027 showed potent antitumor activity in 29% of
      specimens with the wild type gene, and DNA-damaging agents showed such activity
      in 6--18% of specimens. TZT-1027 showed strong antitumor activity in 40% of
      specimens with the mutant type p53 gene, whereas DNA-damaging agents showed such
      activity only in 0--20% of specimens. CONCLUSIONS: We found evidence to suggest
      that TZT-1027 was influenced less by the p53 status of specimens than DNA
      damaging agents. Therefore, TZT-1027 is expected to show similar antitumor
      activity against tumors with a loss of p53 function as well as those with normal
      function of p53 in clinical fields.

PMID- 11466695
TI  - Identification of differentially expressed genes in hepatocellular carcinoma and
      metastatic liver tumors by oligonucleotide expression profiling.
AB  - BACKGROUND: The characterization of differentially expressed genes between
      cancerous and normal tissues is an important step in the understanding of
      tumorigenesis. Global gene expression profiling with microarrays has now offered
      a powerful tool to measure the changes of thousands of genes in any carcinoma
      tissues in an effort to identify these key disease-related genes. To compare the
      gene expression of a primary liver carcinoma, metastatic carcinoma to the liver,
      and normal liver, the authors analyzed tissue from six primary hepatocellular
      carcinomas (HCCs), five colorectal adenocarcinoma metastases to the liver, and
      eight normal livers. METHODS: Samples were processed from total RNA to fragmented
      cRNA and hybridized onto Affymetrix GeneChip(R) expression arrays. Analyses were
      performed to determine the consensus pattern of gene expression for primary liver
      carcinoma, metastatic liver carcinoma, and normal liver tissue and their changes
      in expression level. RESULTS: In hepatocellular carcinoma, 842 genes were
      overexpressed, and 393 genes were underexpressed in comparison with genes of
      normal liver tissue. Of note, 7 of the 20 most increased identified known genes
      previously have been associated with liver carcinoma or other types of cancers.
      The 13 additional identified genes until now have not previously shown strong
      association with cancers. Furthermore, the authors identified 42 genes and 24
      expressed sequence tags that are expressed at a significant level in both HCC and
      metastastic tumors, presenting a list of marker genes indicative of cancerous
      liver tissue. CONCLUSIONS: In this study, genes that can be involved in the
      production of and maintenance of hepatic carcinomas were identified. These data
      offer new insight into genes that are potentially important in the pathogenesis
      of liver carcinoma, as well as additional targets for new strategies for cancer
      therapy and treatment.

PMID- 11466696
TI  - Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive
      disease in patients who have not received stem cell transplantation.
AB  - BACKGROUND: Mylotarg (Wyeth-Ayerst Laboratories, St. Davids, PA) is the brand
      name for a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody
      (gemtuzumab ozogamicin, CMA-676) and has been approved recently for the treatment
      of a subset of elderly patients who have relapsed acute myeloid leukemia (AML).
      Mylotarg is associated with an incidence of approximately 20% Grade 3 or 4
      hyperbilirubinemia and liver transaminitis in this patient population. Hepatic
      venoocclusive disease (VOD) has been reported in patients who have undergone stem
      cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting,
      VOD has been associated very rarely with cytotoxic therapy. METHODS: The authors
      assessed the incidence of VOD in 119 patients who were receiving Mylotarg
      containing non-SCT regimens. VOD was diagnosed through the use of standard
      Seattle and Baltimore criteria. RESULTS: A cohort of 119 (61 previously
      untreated, 58 with relapsed disease) patients with AML (92 patients), advanced
      myelodysplastic syndrome (25 patients), or chronic myeloid leukemia in blast
      phase (2 patients), received Mylotarg-based regimens. Fourteen (12%) developed
      VOD. The diagnosis of VOD was supported by histology in 2 patients and radiologic
      studies in a further 10 patients. Five (36%) of 14 patients with VOD had received
      no prior antileukemic cytotoxic therapy, including 2 patients who received single
      agent Mylotarg therapy. CONCLUSIONS: Mylotarg was shown to be associated with the
      development of potentially fatal VOD in patients with leukemia who had not
      received SCT. VOD occurred when Mylotarg was used either as a single agent or
      when it was given with other cytotoxic agents. VOD occurred in Mylotarg-treated
      patients who had received no prior cytotoxic therapy. The current study concluded
      that risk factors for VOD should be assessed when considering Mylotarg therapy,
      and that attempts to avoid and treat VOD are warranted in patients who receive
      Mylotarg therapy.

PMID- 11466697
TI  - A phase I trial of topotecan and gemcitabine administered weekly for 3
      consecutive weeks to patients with advanced tumors.
AB  - BACKGROUND: The complementary action of gemcitabine and topotecan on DNA
      metabolism suggested the potential for their use in combination chemotherapy.
      Gemcitabine, a synthetic cytidine analogue chain terminator, and topotecan, a
      topoisomerase-1 inhibitor, have been reported to have broad antitumor activity
      and are approved for clinical use. METHODS: The cytotoxicity of the combination
      in various models in vitro was additive. In the current study, the authors
      conducted a Phase I study to determine the recommended Phase II doses and
      toxicity profile of gemcitabine and topotecan when administered weekly in
      combination. Gemcitabine (400--1000 mg/m(2)) was given intravenously over 30
      minutes followed by a 15-minute infusion of topotecan (0.75--2.5 mg/m(2)) weekly
      for 3 consecutive weeks in a 4-week treatment cycle. Thirty-eight patients with
      advanced refractory solid tumors and good performance status were treated.
      RESULTS: Myelosuppression in the form of granulocytopenia and thrombocytopenia
      were the major dose-limiting toxicities. Other toxic effects included anemia,
      nausea, and elevated hepatic transaminases. Partial responses were observed in
      two patients (one with nonsmall cell lung carcinoma and one with pancreatic
      carcinoma). Disease stabilization occurred in five patients (three with
      pancreatic carcinoma, one with rectal carcinoma, and one with metastatic
      carcinoma of an unknown primary site). Gemcitabine, 1000 mg/m(2), and topotecan,
      2.5 mg/m(2), were the maximum tolerated doses for this combination. CONCLUSIONS:
      The results of the current study showed that the combination of weekly
      gemcitabine and topotecan for 3 weeks in a 4-week cycle schedule appeared to be
      well tolerated and was associated with clinical activity. Therefore, this
      combination is recommended for a further Phase II evaluation.

PMID- 11466698
TI  - A phase III study of radiation therapy plus carmustine with or without
      recombinant interferon-alpha in the treatment of patients with newly diagnosed
      high-grade glioma.
AB  - BACKGROUND: The current study was conducted to determine whether the addition of
      interferon-alpha (IFN-alpha) to treatment with radiation therapy and carmustine
      (BCNU) improves time to disease progression or overall survival in patients with
      high-grade glioma. METHODS: Patients with anaplastic astrocytoma, anaplastic
      oligoastrocytoma, glioblastoma multiforme, or gliosarcoma received radiation
      therapy plus BCNU as initial therapy. Subsequently, patients without tumor
      progression at the completion of radiation therapy were stratified by age, extent
      of surgery, tumor grade and histology, Eastern Cooperative Oncology Group
      performance status, and treating institution, and then were randomly assigned to
      receive either BCNU alone (200 mg/m(2) on Day 1) or BCNU (150 mg/m(2) on Day 3)
      plus IFN--alpha (12 million U/m(2) on Days 1-3, Weeks 1, 3, and 5) every 7 weeks
      for a maximum of 6 cycles. RESULTS: Of the 383 patients enrolled in the study,
      275 eligible patients were randomized. There was no significant difference with
      regard to time to disease progression or overall survival between the two groups.
      Patients receiving IFN-alpha experienced more fever, chills, myalgias, and
      neurocortical symptoms including somnolence, confusion, and exacerbation of
      neurologic deficits. Cox multivariate regression models confirmed known favorable
      prognostic variables including younger age, Grade 3 tumor (according to World
      Health Organization criteria), and greater extent of surgery. Cox and
      classification and regression tree analysis models also demonstrated that a
      normal baseline Folstein mini-mental status examination (MMSE) score was
      associated with better prognosis. CONCLUSIONS: IFN-alpha does not appear to
      improve time to disease progression or overall survival in patients with high
      grade glioma and appears to add significantly to toxicity. The baseline MMSE
      score may serve as an independent prognostic factor and warrants further
      investigation.

PMID- 11466699
TI  - Comparing 18-fluoro-2-deoxyglucose positron emission tomography with a
      combination of technetium 99m tetrofosmin single photon emission computed
      tomography and computed tomography to detect recurrent or persistent
      nasopharyngeal carcinomas after radiotherapy.
AB  - BACKGROUND: The diagnostic accuracy of combined computed tomography (CT) and
      technetium 99m tetrofosmin (Tc-TF) single photon emission computed tomography
      (SPECT) of head and neck to differentiate recurrent or residual nasopharyngeal
      carcinomas (NPCs) from benign lesions after radiotherapy was evaluated and
      compared with positron emission tomography (PET) with 18-fluoro-2-deoxyglucose
      (FDG). METHODS: Four months after radiotherapy, 36 patients with NPC underwent Tc
      TF SPECT and CT of head and neck to differentiate recurrent or residual NPC from
      benign lesions. Histopathologic examinations were performed on nasopharyngeal
      biopsies of all 36 patients. RESULTS: Based on the biopsy results, the
      sensitivity, specificity, and accuracy of Tc-TF SPECT were 64%, 96%, and 86%,
      respectively, for differentiation of recurrent or persistent NPC from benign
      lesions. For CT and FDG-PET, the sensitivity, specificity, and accuracy were 73%,
      88%, and 83% and 100%, 96%, 97%, respectively. For the 27 patients with NPC whose
      Tc-TF SPECT and CT results were congruent, the combination of Tc-TF SPECT and CT
      had the same sensitivity, specificity, and accuracy (100%, 96%, and 96%) as FDG
      PET. For the nine patients with NPC with incongruent Tc-TF SPECT and CT results,
      FDG-PET correctly differentiated two benign lesions from seven recurrent/residual
      NPCs. CONCLUSIONS: Although, FDG-PET is the best tool for detecting recurrent or
      residual NPC, combined congruent Tc-TF SPECT and CT results achieved the same
      accuracy as FDG-PET. Therefore, we concluded that FDG-PET could be considered
      only when Tc-TF SPECT and CT give incongruent results.

PMID- 11466700
TI  - The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in
      Australian Ashkenazi Jews: implications for the generality of U.S. population
      data.
AB  - BACKGROUND: Several studies have shown that Ashkenazi Jews in the United States
      and Israel have a high prevalence of the founder mutations BRCA1 185delAG, BRCA1
      5382insC, BRCA2 6174delT, and APC I1307K at frequencies of 1.0--1.1%, 0.2--0.3%,
      0.6--1.4%, and 6.1--7.0%, respectively. The objective of this study was to
      compare the prevalence of these alleles in the Australian Jewish population with
      that of U.S. Jews. Australian Jews have a different history of migration, with
      less opportunity for changes in allele frequency due to conversion or
      intermarriage with non-Jewish Australians. The results obtained therefore can be
      used to assess whether U.S. data can be generalized to other Jewish populations.
      SUBJECTS AND METHODS. Subject samples were ascertained through a screening
      program for Tay-Sachs disease as part of a community-based screening program in
      New South Wales and Victoria. DNA extracted from 1200 deidentified blood samples
      was tested using amplification refractory mutation system polymerase chain
      reaction. RESULTS: The allele frequencies found were as follows: BRCA1 185delAG
      1.25% (95% confidence interval [CI], 0.62--1.88%), BRCA1 5382insC 0.25% (95% CI,
      0--0.53%), BRCA2 6174delT 1.08% (95% CI, 0.50--1.67%), and APC I1307K 8.67% (95%
      CI, 7.07--10.26%). The prevalence of breast carcinoma predisposition alleles
      therefore is greater than 2.5% in Australian Ashkenazim. CONCLUSIONS: There were
      no significant differences between the allele frequencies in Australian
      Ashkenazim and those identified in other studies with similar ascertainment
      strategies, despite the different migration patterns of Australian Jews. This
      suggests the broad applicability of the U.S. and Israeli data, not only to
      Australian Ashkenazim, but also to Ashkenazi communities throughout the world.

PMID- 11466701
TI  - Expression of tumor-associated antigen RCAS1 correlates significantly with poor
      prognosis in nonsmall cell lung carcinoma.
AB  - BACKGROUND: RCAS1 is a recently discovered antigen molecule expressed on the
      membrane of cancer cells, and it acts as a ligand for a putative receptor present
      on immune cells such as T, B and NK cells. It has been suggested that RCAS1
      expression is related to the escape of tumors from immune surveillance. In this
      study, the relation between RCAS1 expression and various clinicopathologic
      variables, including patient prognosis, was investigated in lung carcinoma
      through immunohistochemical analysis. METHODS: One hundred two surgically
      resected nonsmall cell lung carcinoma cases were examined histopathologically by
      means of the monoclonal antibody 22-1-1, which is specific for RCAS1. The
      correlation between RCAS1 expression and the clinicopathologic features of
      patients was evaluated. Moreover, the correlation between RCAS1 expression and
      the survival of patients was analyzed by the Kaplan-Meier method log-rank test,
      and multivariate analysis was performed by using the Cox proportional hazard
      model. RESULTS: The samples of 48 of the 102 lung carcinoma patients (47.1%) were
      positive for RCAS1. There were significant correlations between RCAS1 expression
      and either pathologic staging (P = 0.0003) or tumor differentiation (P = 0.0308).
      The survival time for the RCAS1-positive group was significantly shorter than
      that for RCAS1-negative group (P < 0.0001). Moreover, multivariate analysis for
      overall survival revealed that RCAS1 expression was a significantly independent
      prognostic factor in nonsmall cell lung carcinoma patients. CONCLUSION: These
      results suggested that RCAS1 expression may play an important role in the immune
      escape mechanism and that RCAS1 expression may be a good indicator of poor
      prognosis in patients with nonsmall cell lung carcinoma.

PMID- 11466702
TI  - TNM classification: clarification of number of regional lymph nodes for pNo.

PMID- 11466703
TI  - Leishmania major induces differential expression of costimulatory molecules on
      mouse epidermal cells.
AB  - Levels of expression of costimulatory molecules have been proposed to influence
      the outcome of antigen-specific T cell priming. We found that Leishmania major
      selectively modulated the expression of costimulatory molecules on various
      populations of epidermal cells. B7.2 expression was down-regulated on Thy1.2+
      epidermal cells (keratinocytes) from disease-resistant C3H mice, but not from
      disease-susceptible BALB/c mice. In addition, epidermal cells from BALB/c mice
      showed a down-regulation of B7.1 expression on NLDC 145+ Langerhans cells. In
      vitro T cell priming experiments, using syngeneic epidermal cells as antigen
      presenting cells (APC), showed that the production of IFN-gamma was inhibited
      when either B7.1 or B7.2 signaling pathways were blocked. Blockade of B7.2, but
      not B7.1, significantly inhibited the ability of epidermal cells to induce IL-4
      production from CD4+ T cells. In addition, C3H CD4+ T cells, which were unable to
      secrete detectable levels of IL-4 in cultures with syngeneic APC, were now able
      to secrete IL-4 following presentation of L. major antigens by congenic BALB/K
      epidermal cells. Conversely, C3H epidermal cells supported the priming of BALB/K
      CD4+ T cells for IL-4 production in vitro. Thus, the differential expression of
      B7 molecules on epidermal cells may not represent the sole factor governing the
      polarization of L. major-specific CD4+ T cells in vitro.

PMID- 11466704
TI  - Characterization of murine BATF: a negative regulator of activator protein-1
      activity in the thymus.
AB  - BATF belongs to the AP-1/ATF superfamily of transcription factors and forms
      heterodimers with Jun proteins to bind AP-1 consensus DNA. Unlike Fos/Jun
      heterodimers which stimulate gene transcription, BATF/Jun heterodimers are
      transcriptionally inert and inhibit biological processes that are associated with
      the overstimulation of AP-1 activity. Here, we describe the murine BATF cDNA and
      genomic clones and map the BATF locus to chromosome 12 D2-3. Using in situ
      hybridization of BATF mRNA, we show that BATF gene expression is highly
      restricted, with the most prominent signals detected in the thymus. BATF mRNA
      levels are regulated differentially during discrete stages of T cell development
      and are up-regulated following activation of T cells in the periphery. To
      demonstrate the impact of BATF on AP-1 activity in vivo, AP-1 luciferase reporter
      mice were crossed to transgenic mice overexpressing BATF exclusively in thymic T
      cells. Results show that elevated levels of BATF protein correlate with reduced
      transactivation by AP-1. Since the differential regulation of AP-1 activity is
      linked to key transitions in the developing immune system, our observations
      support a critical role for BATF in determining the overall level of AP-1
      activity, and thus AP-1 target gene expression, in specific T cell subtypes.

PMID- 11466705
TI  - Development of song responses in the zebra finch caudomedial neostriatum: role of
      genomic and electrophysiological activities.
AB  - Zebra finches first form demonstrable memories of specific songs between 25 and
      35 days of age--several days after fledging from the nest. What accounts for the
      late onset of specific song memory formation? Here we investigated physiological
      development of the caudomedial neostriatum (NCM), part of the avian analogue of
      auditory cortex and a probable component of the system involved in song
      perception. Two types of physiological responses were characterized:
      electrophysiological (single-unit spike rate) and genomic (induction of the
      immediate early gene zenk, also known as zif-268, egr-1, ngfi-a, krox-24). We
      found that by day 20, zebra finches already have robust electrophysiological
      responses in NCM to song stimulation. Spike activity was greater in response to
      conspecific songs compared to heterospecific songs, white noise, or tones, and
      approximately 10% of the units showed selective responses to forward versus
      reversed songs. In contrast, at this age the zenk gene is expressed at a
      constitutively high level and undergoes no further induction in response to song
      presentation. At day 30, electrophysiological responses remained similar, but the
      zenk gene began to shift from a constitutive to an inducible pattern of
      expression. These results are consistent with a general role for NCM in the
      representation of song auditory patterns, and with a role for zenk gene
      expression in governing the efficiency of specific song memory storage at
      different ages.

PMID- 11466706
TI  - Neuronal differentiation and long-term survival of newly generated cells in the
      olfactory midbrain of the adult spiny lobster, Panulirus argus.
AB  - The fate of continuously generated cells in the soma clusters of the olfactory
      midbrain of adult spiny lobsters, Panulirus argus, was investigated by in vivo
      pulse-chase experiments with the proliferation marker 5-bromo-2'-deoxyuridine
      (BrdU) combined with immunostainings for neuropeptides of mature neurons. A BrdU
      injection after a survival time (ST) of 14 h labeled about 100 nuclei in the
      lateral soma clusters (LC), comprised of projection neurons, and about 30 nuclei
      in the medial soma clusters (MC), comprised of local interneurons. The BrdU
      positive nuclei were confined to small regions at the inside of these clusters,
      which also contain nuclei in different phases of mitosis and thus represent
      proliferative zones. After STs of 2 weeks or 3 months, the number of BrdU
      positive nuclei was doubled, indicating a mitosis of all originally labeled
      cells. Dependent on ST, the BrdU-positive nuclei were translocated from the
      proliferative zones towards the outside of the clusters, where somata of mature
      neurons reside. Immunostainings with antibodies to the neuropeptides FMRFamide
      and substance P, both of which label a large portion of somata in the MC and a
      pair of giant neurons projecting into the LC, revealed that in both clusters the
      proliferative zones are surrounded by, but are themselves devoid of, labeling. In
      the MC, some BrdU-positive somata were double-labeled by the FMRFamide antibody
      after an ST of 3 months, and by the substance P antibody after STs of 6 and 11/14
      months, but not after 3 months. In the LC, BrdU-positive somata after an ST of 3
      months partially and after 6 and 11/14 months widely overlapped with the
      arborizations of the giant neurons, indicating the establishment of synaptic
      input. The experiments show that cells generated in proliferative zones in the LC
      and MC of adult spiny lobsters after a final mitosis differentiate into neurons
      within months, survive for at least 1 year, and are integrated into the circuitry
      of the olfactory midbrain. A new hypothesis about the mechanism of adult
      neurogenesis in the central olfactory pathway of decapod crustaceans is
      developed, linking it to neurogenesis during embryonic and larval development.

PMID- 11466707
TI  - Gap junctional coupling between progenitor cells at the retinal margin of adult
      goldfish.
AB  - We prepared living slice preparations of the peripheral retina of adult goldfish
      to examine electrical membrane properties of progenitor cells at the retinal
      margin. Cells were voltage-clamped near resting potential and then stepped to
      either hyperpolarizing or depolarizing test potentials using whole-cell voltage
      clamp recordings. Electrophysiologically examined cells were morphologically
      identified by injecting both Lucifer Yellow (LY) and biocytin. All progenitor
      cells examined (n = 37) showed a large amount of passively flowing currents of
      either sign under suppression of the nonjunctional currents flowing through K(+)
      and Ca(2+) channels in the cell membrane. They did not exhibit any voltage-gated
      Na(+) currents. Cells identified by LY fills were typically slender. As the
      difference between the test potential and the resting potential increased, 13 out
      of 37 cells exhibited symmetrically voltage- and time-dependent current decline
      on either sign at the resting potential. The symmetric current profile suggests
      that the current may be driven and modulated by the junctional potential
      difference between the clamping cell and its neighbors. The remaining 24 cells
      did not exhibit voltage dependency. A gap junction channel blocker, halothane,
      suppressed the currents. A decrease in extracellular pH reduced coupling currents
      and its increase enhanced them. Dopamine, cAMP, and retinoic acid did not
      influence coupling currents. Injection of biocytin into single progenitor cells
      revealed strong tracer coupling, which was restricted in the marginal region.
      Immature ganglion cells closely located to the retinal margin exhibited voltage
      gated Na(+) currents. They did not reveal apparent tracer coupling. These results
      demonstrate that the marginal progenitor cells couple with each other via gap
      junctions, and communicate biochemical molecules, which may subserve or interfere
      with cellular differentiation.

PMID- 11466708
TI  - Calcium imaging of epileptiform events with single-cell resolution.
AB  - Epileptic discharges propagate through apparently normal circuits, although it is
      still unclear how this recruitment takes place. To understand the role of
      different classes of neurons in neocortical epilepsy, we have developed a novel
      imaging assay that detects which neurons participate in epileptiform discharges.
      Using calcium imaging of neuronal populations during bicuculline-induced
      spontaneous epileptiform events in slices from juvenile mouse somatosensory
      cortex, we find that fast calcium transients correlate with epileptiform field
      potentials and intracellular depolarizing shifts and can be used as an optical
      signature that a given neuron has participated in an epileptiform event. Our
      results demonstrate a novel method to characterize epileptiform events with
      single-cell resolution. In addition, our data are consistent with an important
      role for layer 5 in generating neocortical seizures and indicate that subgroups
      of neurons are particularly prone to epileptiform recruitment.

PMID- 11466709
TI  - Expression and localization of agrin during sympathetic synapse formation in
      vitro.
AB  - Agrin is a motoneuron-derived signaling factor that plays a key organizing role
      in the initial stages of neuromuscular synapse formation. Agrin is expressed in
      other regions of the developing central and peripheral nervous systems, however,
      raising the possibility that it also directs the formation of some interneuronal
      synapses. To address this question, we have examined the expression and
      localization of agrin during formation of cholinergic, interneuronal synapses in
      the sympathetic system. In the superior cervical ganglia (SCG) in vivo, we found
      that agrin is highly expressed, and that it is present at, but is not limited to,
      synapses. In SCG neuronal cultures that were treated with ciliary neurotrophic
      factor to induce a uniform cholinergic phenotype, we found that agrin
      immunostaining colocalized precisely with cholinergic terminals and aggregates of
      neuronal acetylcholine receptor on the neuronal cell bodies and dendrites.
      Moreover, we found that alpha-dystroglycan, which is a potential receptor for
      agrin, is also concentrated at these cholinergic synaptic contacts. Finally, the
      SCG neurons expressed the C-terminal isoform of agrin that is neural-specific and
      highly active in synaptogenesis, and also the N-terminal splice isoform that
      occurs as a type II transmembrane protein. These findings show that agrin is
      specifically localized at sympathetic synapses in vitro, and are consistent with
      it playing a role in interneuronal synapse formation.

PMID- 11466710
TI  - Intellectual disability and the myth of the changeling myth.
AB  - This article investigates the historical sources for the idea of the "changeling"
      or substitute child as an explanation for congenital intellectual disability. Pre
      modern sources for this idea are elite and theological as much as popular and
      folkloric, nor do they refer to intellectual disability in any sense recognizable
      to us. Rather, both the concept of intellectual disability and the notion of a
      transhistorical changeling myth emerge from the historical core of modern
      psychology.

PMID- 11466711
TI  - Alvin W. Gouldner and industrial sociology at Columbia University.
AB  - Alvin W. Gouldner (1920--1980) was a prolific sociologist of the post-World War
      II era who spent the early part of his career (the 1950s) in the field of
      industrial sociology. A case study of Gouldner's early life and career is useful
      insofar as it intertwines with the development of industrial sociology as a
      distinct subfield within sociology. Through this analysis we are also better able
      to understand how and in what ways a burgeoning organizational studies program
      developed at Columbia University during the 1940s. This analysis of the
      historical and cultural contexts within which Gouldner came to prominence as an
      industrial sociologist at Columbia, and the intellectual program that resulted,
      can also help shed light on more recent trends in organizational studies.

PMID- 11466712
TI  - Socialist psychotherapy and its dissidents.
AB  - This article focuses on the history of psychotherapeutic theory and practice in
      socialist East Germany before the fall of the Berlin Wall in 1989. The "official"
      pre-1989 socialist history of East German psychology is juxtaposed to
      psychotherapists' post-1989 oral history of the development of Socialist
      psychological theory and practice. These reconstructive histories draw on
      embryonic therapeutic practices that diverged from the dominant socialist
      paradigm. Their existence exemplifies how a state-driven high modernist scheme
      for remaking society can fail as it does not account for the complex relationship
      between a state's abstract knowledge and local practices. Moreover, the emphasis
      therapists put on the prevalence of these alternative practices also reveals how
      the present post-socialist context becomes an interpretative resource for
      reconstructing their past. By emphasizing these practices they try to bridge the
      gap between their past and current practices so as to minimize the transformation
      that has taken place.

PMID- 11466715
TI  - Response evaluation criteria in solid tumors (RECIST): new guidelines.

PMID- 11466716
TI  - Plasma levels of natriuretic peptides in relation to doxorubicin-induced
      cardiotoxicity and cardiac function in children with cancer.
AB  - BACKGROUND: Anthracyclines are effective anticancer drugs for childhood cancer
      with dose-limiting cardiotoxicity. Children who have received anthracyclines thus
      need periodical cardiac evaluation. The plasma levels of atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP) have been shown to increase in
      proportion to severity of cardiac dysfunction. We examined whether plasma levels
      of ANP and BNP, in addition to echocardiographic evaluation, can be used as
      specific markers for doxorubicin-induced cardiotoxic effects in children.
      PROCEDURE: Consecutively, 34 patients (18 boys and 16 girls) who had previously
      received doxorubicin-containing chemotherapy were enrolled in this study. Plasma
      ANP and BNP were assayed simultaneously at the time of first cardiac function
      evaluation by echocardiography. RESULTS: Of the 34 patients, 8 (23.5%) had left
      ventricular dysfunction as assessed by echocardiography. Both ANP and BNP plasma
      levels in these patients were significantly elevated in comparison with healthy
      controls (P < 0.01) or patients with normal cardiac function (P < 0.05). It
      should be also noted that ANP and BNP levels were correlated significantly with
      cardiac systolic function, but not with diastolic function. CONCLUSIONS: These
      results suggest that plasma ANP and BNP levels could be markers for doxorubicin
      induced cardiotoxicity in children. Measurement of natriuretic peptide levels
      during treatment may allow earlier-identification of individuals at risk for
      severe cardiac damage.

PMID- 11466717
TI  - Outcome of acute lymphoblastic leukemia in children with AL90 regimen: impact of
      response to treatment and sex difference on prognostic factors.
AB  - BACKGROUND: In our previous studies, the outcome of high-risk ALL was still poor.
      In the present study, all children with ALL were classified into three groups and
      treated with a new regimen (AL90). PATIENTS AND METHODS: Between 1990 and 1996,
      220 children with ALL, treated with the AL90 regimen, were classified into three
      risk groups: low, intermediate, and high: LR, IR, and HR, respectively. The
      protocol consisted of three- to five-drug induction, consolidation with
      intermediate-dose methotrexate and/or cytarabine, mercaptopurine and
      cyclophosphamide, four-drug intensification, and sequential maintenance
      therapies. Only intrathecal chemotherapy was used for CNS prophylaxis in the LR
      group, whereas cranial irradiation was added for the IR and HR groups. RESULTS:
      The number of eligible patients was 91: LR group, 71: IR group, and 58: HR group.
      Complete remission (CR) was obtained in > 98% of the LR and IR groups, while only
      88% achieved CR in the HR group. The 5-year event-free survival (EFS) rate was
      67.4% in all patients: 70.4% in the LR group, 71.7% in the IR group, and 57.5% in
      the HR group. With respect to the previous study, EFS in the HR group who showed
      positive residual leukemia at 14 days was improved, whereas EFS in boys versus
      girls was significantly lower (48.8% : 85.7%, P = 0.02). CONCLUSIONS: In high
      risk ALL, the rate of induction failure was high and boys had a worse outcome,
      calling for improvements in induction therapy and a specific approach for boys.

PMID- 11466718
TI  - Pneumocystis carinii pneumonia during maintenance treatment of childhood acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a wellknown risk among
      patients with deficient T-cell function such as children treated for acute
      lymphoblastic leukemia (ALL). The purpose of this study was to estimate the risk
      for PCP during maintenance treatment (MT) to identify patients at risk who could
      benefit from prophylaxis. PROCEDURE: We registered all episodes of PCP during MT
      in 71 children diagnosed between January 1992 and June 1997 with non-B-cell ALL
      at The Copenhagen University Hospital. Sulphametoxazole and trimetroprim
      (SMX/TMP) prophylaxis against PCP was given during induction and consolidation
      therapy but stopped prior to MT with oral methotrexate/6-mercaptopurine. Patients
      with standard (SR), intermediate (IR), and high risk (HR) ALL started MT at 3, 8,
      and 15 months from diagnosis, respectively. RESULTS: The HR group had a cumulated
      risk of 70% for developing PCP, whereas the risk for PCP in children with IR and
      the SR was 11 and 8%, respectively (P < 0.0001). All but one of these 13 cases of
      PCP occurred within 8 months after cessation of SMX-TMP prophylaxis. CONCLUSIONS:
      The higher incidence of PCP among HR compared to non-HR patients following
      cessation of SMX/TMP prophylaxis probably reflects the significantly longer T
      cell suppressive consolidation therapy in this group. The very low incidence of
      PCP during the later part of MT emphasizes that methotrexate/6-mercaptopurine MT
      have more impact on B-cell than on T-cell function. TMP/SMX prophylaxis should be
      recommended for all children treated for ALL.

PMID- 11466719
TI  - Benign outcome of RSV infection in children with cancer.
AB  - BACKGROUND: High case-fatality rates have been reported among adults who develop
      respiratory syncytial virus (RSV) infection while being treated for oncologic
      diseases, particularly after bone marrow transplantation. Previous reports of RSV
      infection among children with primary and acquired immunodeficiencies describe
      increased morbidity compared with that seen in immunocompetent children, but
      there have been few reports describing the outcome of RSV infection specifically
      among pediatric oncology patients. METHODS: We retrospectively reviewed the
      charts of all children being treated by the Pediatric Oncology Service at
      Memorial Sloan-Kettering Cancer Center who had positive tests for RSV between the
      Fall of 1994 and the Spring of 1998. Patients on the BMT Service were excluded
      from this analysis. RESULTS: Eighteen RSV infections were identified among
      pediatric oncology patients, who were being treated with aggressive,
      predominantly alkylator-based chemotherapy for a variety of oncologic diagnoses.
      Nine episodes of RSV infection (50%) were treated with specific antiviral
      therapy. Only one death less than 100 days from the diagnosis of RSV infection
      occurred among these 18 patients and was attributed to progressive leukemia. The
      remaining patients recovered fully, although three were readmitted with
      respiratory symptoms within two weeks of discharge. Seven patients had concurrent
      infection with other pathogenic organisms. CONCLUSIONS: In striking contrast with
      the outcome of RSV infection in adult oncology patients, there may be low
      mortality associated with RSV infection in pediatric oncology patients. It is
      possible that scheduled anti-neoplastic therapy need not be delayed for these
      patients when the diagnosis of RSV infection is made.

PMID- 11466720
TI  - Primary Ewing tumor of the vertebrae: clinical characteristics, prognostic
      factors, and outcome.
AB  - BACKGROUND: Fewer than 10% of Ewing family of tumors (EFT) arise in the
      vertebrae. Little information is available regarding the clinical presentation
      and outcome of these tumors. PROCEDURE: We reviewed the clinical features,
      prognostic factors, and outcome of EFT of the spine identified at our institution
      between 1962 and 1999. RESULTS: Thirty-three (10%) of 344 patients with EFT had a
      primary vertebral tumor. There were 21 (64%) males. Median age at diagnosis was
      13.3 years. Six patients had metastatic disease and 10 had tumors > or = 8 cm in
      diameter. Primary sites were sacral (13), thoracic (10), lumbar (8), and cervical
      (2) vertebrae. We found no association between the affected spinal region and
      outcome, although sacral tumors were associated with delayed diagnosis (4 vs. 2
      months after onset of symptoms, P = 0.076). Pain (n = 32) and neurologic deficits
      (n = 31; 82% motor, 58% sensory, 42% bladder, 27% bowel) were the most common
      presenting features. All patients received combination chemotherapy and local
      radiotherapy. With a median follow up of 9.7 years, 5-year survival and event
      free survival ( +/- SD) estimates were 48.1% (8.9%) and 35.6% (8.6%),
      respectively, comparable to those of other patients with EFT. Outcome was better
      for patients with tumor size < 8 cm (P = 0.008) or localized disease (P = 0.084).
      Treatment era and specific tumor site did not affect outcome. CONCLUSIONS:
      Outcomes are similar for primary EFT of the spine and primary EFT in other sites.
      Unlike others, we found that patients with sacral tumors did not fare worse than
      patients with tumors at other spinal sites.

PMID- 11466721
TI  - Conformal proton radiation treatment for retroperitoneal neuroblastoma:
      introduction of a novel technique.
AB  - BACKGROUND: Postoperative irradiation for locoregionally advanced neuroblastoma
      requires coverage of the paraspinal retroperitoneum. The proximity of both
      kidneys and the liver, and a more complex target configuration, can pose a
      dosimetric challenge for conventional X-ray treatment and intraoperative
      irradiation. We utilized proton radiation therapy (PRT) to reduce dose to
      uninvolved kidneys, liver, intestine, and spinal cord. PROCEDURE: A 4-year-old
      male underwent PRT for neuroblastoma of the right adrenal gland, following
      chemotherapy and delayed surgical resection. Clinical target volume (CTV), boost
      volume, and normal structures were outlined on the 3D treatment planning CT scan.
      The patient received 25.2 CGE (cobalt Gray equivalent) to the CTV and 34.2 CGE to
      the boost region, using 1.8 CGE per fraction, five treatments per week. Dose
      volume histograms (DVHs) were obtained for target and nontarget structures.
      RESULTS: The 95% isodose volume enclosed CTV and boost volumes. The dose to 50%
      of the ipsilateral kidney, with tumor involvement of the medial renal surface,
      was < or = 16 CGE (47% of prescribed total dose). Doses to 50% and 20% of the
      contralateral kidney in close proximity to deep left-side, paraspinal soft tissue
      involvement were restricted to 1 CGE and 10 CGE, respectively. Eighty percent of
      the liver received 27 CGE (80% of prescribed dose). Using a patch technique,
      unique to charged particle therapy, the spinal cord was almost completely spared
      during boost volume irradiation. CONCLUSIONS: PRT can achieve excellent dose
      conformity for advanced retroperitoneal, paraspinal lesions, while respecting
      normal tissue tolerance levels.

PMID- 11466722
TI  - Prediction of health behaviors in pediatric cancer survivors.
AB  - BACKGROUND: It is important to understand the factors that motivate survivors of
      childhood cancer to engage in healthy behaviors. This is because of their
      susceptibility to adverse late effects from their malignancy and its treatment.
      We specifically examined sociodemographic and health perception variables as
      predictors of health-protective behaviors in pediatric cancer survivors.
      PROCEDURE: Forty-six patients, ages 10--18 years, who were previously treated for
      cancer and were 1--4 years off-therapy, were assessed using a battery of testing
      instruments. RESULTS: Preadolescent and adolescent cancer survivors reported
      moderately frequent practice of a variety of health-protective behaviors. The
      prevalence of risky health behaviors, as indicated by alcohol and tobacco use,
      was low. Regression analyses indicated that the practice of health-protective
      behaviors was best predicted by patient's age and socioeconomic status (SES);
      younger adolescents and patients from higher SES more frequently engaged in
      healthy behaviors. Health perception variables were not significantly related to
      health-protective behaviors. This was true despite findings that survivors
      perceived themselves to be vulnerable to health problems, identified a need to
      protect their health, and perceived their health outcomes to be largely
      determined by their own behaviors. CONCLUSIONS: Sociodemographic factors should
      be kept in mind when designing interventions to promote continuing good health
      for young cancer survivors. Also to be included is the assessment of specific
      health risks secondary to the cancer therapies given. Risk counseling that
      recognizes and builds on these variables will be most effective in helping this
      patient population observe sound health habits.

PMID- 11466723
TI  - Pancreatoblastoma in childhood: clinical course and therapeutic management of
      seven patients.
AB  - BACKGROUND: To analyze the clinical course of pancreatoblastoma in children and
      to propose management and therapy. PROCEDURE: Retrospective review of seven cases
      of pancreatoblastoma treated in France over a 20-year period and literature
      review. RESULTS: Median age of patients was 6 years. The tumor was well
      encapsulated in one patient and had direct extension to adjacent tissues in two
      others. Three patients had regional lymph node involvement and one had liver
      metastases. The tumor arose in the head of the pancreas in three children, in the
      tail and body in two and in the tail and in the body, one each. Elevation of AFP
      serum levels was noted in four out of 6 cases. Five tumor resections were
      performed, one initially and 4 after neoadjuvant chemotherapy, and cisplatin plus
      doxorubicin seemed effective. Two children received post-operative irradiation
      because of incomplete resection. In all, four children are disease free with a
      median follow-up of 50 months ( range, 5--120 months) : one had a complete
      removal of tumor at diagnosis and no further treatment, three had unresectable
      tumor at diagnosis and received neoadjuvant chemotherapy with cisplatin and
      doxorubicin. One of them also received post-operative irradiation. CONCLUSIONS:
      Pancreatoblastoma is a curable tumor. Examination of serum AFP levels may be
      useful for diagnosis and to follow the course of the disease. Complete resection
      is the treatment of choice. However, tumor is often unresectable at diagnosis and
      preoperative chemotherapy is needed to reduce tumor volume. We suggest a regimen
      that include cisplatin and doxorubicin. In patients with incompletely resected
      disease, postoperative radiation may be indicated.

PMID- 11466724
TI  - Primary pancreatic lymphoma presenting as acute pancreatitis in a child.

PMID- 11466725
TI  - Childhood cancer etiology: recent reports.

PMID- 11466726
TI  - Palliative and terminal care for dying children; proposals for better care.

PMID- 11466727
TI  - Maturation in the primary and metastatic lesions of fetal rhabdomyomatous
      nephroblastoma.

PMID- 11466728
TI  - Acute lymphoblastic leukemia presenting with extensive skeletal lesions and bone
      marrow necrosis.

PMID- 11466729
TI  - Experience with tamoxifen/etoposide in the treatment of a child with
      myxopapillary ependymoma.

PMID- 11466730
TI  - Non-identical twin sisters concordant for Langerhans cell histiocytosis and
      discordant for secondary acute promyelocytic leukemia.

PMID- 11466731
TI  - Congenital Langerhans cell histiocytosis with isolated skin involvement.

PMID- 11466732
TI  - Fibromatosis in the paramandibular region.

PMID- 11466733
TI  - Inflammatory pseudotumor of the spleen in a child.

PMID- 11466734
TI  - Anticancer drugs from nature.

PMID- 11466737
TI  - The female genital system of Ooperipatellus decoratus (Onychophora,
      Peripatopsidae): an ultrastructural study.
AB  - The female genital system of the oviparous peripatopsid Ooperipatellus decoratus
      consists of an ovary, oviducts equipped with receptacula seminis and additional
      pouches, uteri, and a vagina. It is examined using transmission and scanning
      electron microscopy. The ovary is made up of paired ovarian tubes united
      anteriorly and posteriorly and differentiated into a sterile dorsal part and a
      fertile ventral part with exogenous oocytes. Fertilization presumably occurs in
      the oviducts once the oocytes pass the receptaculum seminis. Although the
      receptacula seminis have been reported to occur in juvenile O. decoratus females
      only, the present study reveals that they are present in adult females as well.
      Their wall consists of a cuboidal epithelium covered with a thin collagen-muscle
      layer. The additional pouches are projections of the oviducts facing the
      receptacula seminis. They are distally closed to the haemocoel by a flattened
      epithelium and lack external muscle cells. A thin collagen layer is only found
      proximally. The uteri are characterized by a columnar epithelium with folded cell
      membranes allowing extension of the uteri, thus facilitating the passage of the
      large uterine eggs towards the vagina. Another dominating feature of the uteri is
      a distally increasing secretory production, which probably contributes to chorion
      development. Cilia occurring along the entire length of the uteri are considered
      to assist in the transport of eggs towards the vagina.

PMID- 11466738
TI  - Mispatterning in the ommatidia of Apis mellifera pupae treated with a juvenile
      hormone analogue.
AB  - To further understand the function of morphogenetic hormones in honeybee eye
      differentiation, the alterations in ommatidial patterning induced by
      pyriproxyfen, a juvenile hormone (JH) analogue, were studied by scanning and
      transmission electron microscopy. Prepupae of prospective honeybee workers were
      treated with pyriproxyfen and the effects on ommatidial differentiation were
      described at the end of the pupal development. The results show that the entire
      ommatidia, i.e., the dioptric as well as the receptor systems, were affected by
      the JH analogue. The wave of ommatidial differentiation, which progresses from
      the posterior to the anterior region of the pupal eyes, was arrested. In treated
      pupae, the rhabdomeres only differentiated at the apical axis of the retinula,
      the secondary and tertiary pigment cells did not develop their cytoplasm
      protrusions, and the cone cell quartet did not pattern correctly. Simultaneously,
      an intense vacuolization was observed in cells forming ommatidia. In a previous
      study we showed that pyriproxyfen exerts an inhibition on pupal ecdysteroid
      secretion. In this sense, the arrested ommatidial differentiation in pyriproxyfen
      treated pupae could be due to a secondary effect resulting from an alteration in
      pupal ecdysteroid titers.

PMID- 11466739
TI  - On the osteology and myology of catfish pectoral girdle, with a reflection on
      catfish (Teleostei: Siluriformes) plesiomorphies.
AB  - The configuration of the pectoral girdle bones and muscles of numerous catfishes
      was studied in detail and compared with that of other siluriforms, as well as of
      other teleosts, described in the literature. The pectoral girdle of catfishes is
      composed of only three bones, which probably correspond to the posttemporo
      supracleithrum (posttemporal + supracleithrum), scapulo-coracoid (scapula +
      coracoid), and cleithrum of other teleosts. These latter two bones constitute the
      place of origin of the pectoral girdle muscles. Two of these muscles are related
      to the movements of the pectoral fin. These two muscles correspond, very likely,
      to the abductor superficialis and to the adductor superficialis of other
      teleostean fishes. In relation to the pectoral spine (thickened first pectoral
      fin ray), it is usually moved by three well-developed muscles, which are probably
      homologous with the arrector ventralis, arrector dorsalis, and abductor profundus
      of nonsiluriform teleosts. The morphological diversity and the plesiomorphic
      configuration of these muscles, as well as of the other catfish pectoral girdle
      structures, are discussed.

PMID- 11466740
TI  - Rotation of middle ear ossicles during cetacean development.
AB  - Cetacean middle ears are unique among mammals in that they have an elongated
      tympanic membrane, a greatly reduced manubrium mallei, and an incudal crus longum
      that is shorter than the crus breve. Elongation of the tympanic membrane and
      reduction of the manubrium is thought to be related to an evolutionary rotation
      of the incus and malleus out of the plane of the tympanic membrane. We examined
      if rotation also occurs during ontogeny by comparing the middle ears of two
      species of dolphins (Delphinus delphis, Stenella attenuata) at different stages
      of development. We observed that: the incus has the body and crural proportions
      as in terrestrial mammals early in development; the incudomallear complex rotates
      approximately 90 degrees following ossification; the tympanic membrane is not
      elongated until relatively late in development. Therefore, some of the unique
      characteristics of the cetacean middle ear develop as modifications of an
      initially terrestrial-like morphology.

PMID- 11466741
TI  - The allantoplacenta of Mabuya mabouya (Sauria, Scincidae).
AB  - Analysis of placentation in the final stages of development in Mabuya mabouya
      shows that the placenta is formed by the apposition of the chorioallantois to the
      uterine mucosa implicating the entire embryonic chamber, because the allantoic
      vesicle invades all the exocoelom. The chorioallantoic placenta presents the
      features proper of a type IV allantoplacenta. However, in the mesometrial area
      peripheral to the placentome, we found that the paraplacentome is an additional
      zone specialized for histotrophic transfer, and is separated from the rest of the
      embryonic chamber by a chorionic invagination formed of polymorphic cells. The
      chorionic areolae are components of the embryonic hemisphere; they are in
      apposition to an endometrium with columnar epithelial cells and several glands
      that secrete toward the cavity of the areolae. They are observed only in the
      preparturition stage, probably operating in maternal-fetal transfer of nutrients
      during the last embryonic growth stage. The mesometrial hemisphere possesses
      specializations related to histotrophic nutrition (placentome, paraplacentome,
      and chorionic areolae), while in the abembryonic hemisphere there is an
      allantoplacenta of mixed function, with capacity for histotrophic nutrition and
      for gas exchange. The absorptive plaques are small rounded areas constituted by
      chorionic cells similar to the paraplacentomal chorionic cells, in intimate
      apposition with a secretory uterine epithelium. Separating the absorptive plaques
      are respiratory segments histologically similar to the type I allantoplacenta.
      The additional histotrophic areas found for this species demonstrate the great
      specialization of this allantoplacenta, and support the highest degree of
      matrotrophy among reptiles reached in the Neotropical Mabuya.

PMID- 11466742
TI  - Postparietal and prehatching ontogeny of the supraoccipital in Alligator
      mississippiensis (Archosauria, Crocodylia).
AB  - The first record of the postparietal bone of Alligator mississippiensis,
      documented by transverse histological sections, is presented. It is the first
      evidence of the presence of this bone within Recent reptiles. The postparietal is
      present in a specimen with a head length of 32.3 mm. The bone is a small dermal
      plate lying ventrally and posteriorly to the posterior margin of the parietal and
      dorsally to the trabecular bone, forming a dorsal surface of the supraoccipital
      portion of the neural endocranium. The trabecular bone develops perichondrally
      from the dorsal surface of the tectal cartilaginous bridge spanning between the
      dorsal portions of the otic capsules and occipital pilae. The bridge probably
      represents the fused tectum synoticum posterior plus tectum posterius. Later in
      ontogeny, the bridge ossifies endochondrally. The endochondrally ossifying bridge
      together with its perichondrally ossifying trabecular bone form the future
      supraoccipital. The trabecular bone is the integral part of the cranial
      endoskeleton and ontogenetically distinct from the dermal postparietal bone.

PMID- 11466743
TI  - Morphology and histochemistry of the hyolingual apparatus in chameleons.
AB  - We reexamined the morphological and functional properties of the hyoid, the
      tongue pad, and hyolingual musculature in chameleons. Dissections and
      histological sections indicated the presence of five distinctly individualized
      pairs of intrinsic tongue muscles. An analysis of the histochemical properties of
      the system revealed only two fiber types in the hyolingual muscles: fast
      glycolytic and fast oxidative glycolytic fibers. In accordance with this
      observation, motor-endplate staining showed that all endplates are of the en
      plaque type. All muscles show relatively short fibers and large numbers of motor
      endplates, indicating a large potential for fine muscular control. The connective
      tissue sheet surrounding the entoglossal process contains elastin fibers at its
      periphery, allowing for elastic recoil of the hyolingual system after prey
      capture. The connective tissue sheets surrounding the m. accelerator and m.
      hyoglossus were examined under polarized light. The collagen fibers in the
      accelerator epimysium are configured in a crossed helical array that will
      facilitate limited muscle elongation. The microstructure of the tongue pad as
      revealed by SEM showed decreased adhesive properties, indicating a change in the
      prey prehension mechanics in chameleons compared to agamid or iguanid lizards.
      These findings provide the basis for further experimental analysis of the
      hyolingual system.

PMID- 11466744
TI  - Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment
      success?
AB  - The traditional aim of Alzheimer's disease treatment in clinical trials has been
      to improve cognitive abilities. It has become increasingly clear, however, that
      other aspects are important in assessing treatment responses. A group of 10
      physicians recently gathered to review the current criteria for assessing
      treatment success in Alzheimer's disease. While cognition has been previously
      viewed as the primary measure of efficacy, areas such as functional abilities,
      behaviour, caregiver burden, quality of life and resource utilization all need to
      be comprehensively assessed to fully evaluate treatment effects in patients with
      Alzheimer's disease, as well as their impacts on caregivers and society.
      Postponing or slowing decline in any of these areas may represent an important
      benefit and should be considered as an outcome measure in clinical trials,
      clinical practice and decision-making about healthcare budgets. Accepted
      instruments are available for assessing outcomes in each aspect of Alzheimer's
      disease, but they need to be selected carefully to provide valid, meaningful
      data. Some of the most frequently used outcome measures in Alzheimer's disease
      are reviewed. Using expanded criteria for treatment success and clinically
      relevant outcome measures, data from currently available studies show that
      cholinesterase inhibitors produce clinically meaningful long-term benefits in
      multiple domains in patients with Alzheimer's disease.

PMID- 11466745
TI  - Neuropathological correlates to clinically defined dementia with Lewy bodies.
AB  - OBJECTIVES: To analyse the neuropathological changes behind clinically defined
      dementia with Lewy bodies (clinDLB) compared with clinically diagnosed
      Alzheimer's disease (clinAD). METHODS: The prevalence of neuropathological
      findings in 48 clinDLB and 45 clinAD cases was compared. Sixteen clinDLB and 10
      clinAD cases were reassessed with alpha-synuclein staining for Lewy bodies (LB).
      RESULTS: Alzheimer pathology was found in 81% of the clinDLB and 93% of the
      clinAD cases. The clinDLB group had a higher prevalence of frontal white matter
      pathology, mostly of ischemic type, and a more severe degeneration of the
      substantia nigra compared with the clinAD group. In hematoxylin-eosin staining,
      LBs were identified in seven (15%) of the clinDLB and in four (9%) of the clinAD
      group. In alpha-synuclein staining, 38% of the clinDLB and 40% of the clinAD
      cases exhibited LBs. The cases without LBs, in the clinDLB group, had AD
      pathology in combination with frontal white matter disease. Vascular pathology of
      significant degree was prevalent in more than 40% of all the cases with verified
      LBs regardless of clinical diagnosis. CONCLUSION: Consecutive dementia cases,
      fulfilling the clinical consensus criteria for DLB, may exhibit combinations of
      neuropathological changes which in themselves can explain the clinical picture of
      DLB even when LBs are absent.

PMID- 11466747
TI  - High prevalence of anxiety symptoms in hospitalized geriatric patients.
AB  - OBJECTIVE: To examine the prevalence of anxiety symptoms in hospitalized
      geriatric patients. DESIGN: Controlled cross-sectional study. SUBJECTS: Ninety
      eight geriatric in-patients and 68 healthy home-dwelling controls of similar age
      recruited from senior citizen centres. OUTCOME MEASURE: Anxiety measured as a
      current emotional state by Spielberger's State-Trait Anxiety Inventory (STAI).
      RESULTS: The geriatric patients scored significantly higher than the controls.
      Applying Spielberger's recommended cut-off of 39/40 on the STAI sumscore, 41% of
      the female and 47% of the male geriatric patients might be suspected of suffering
      from significant anxiety symptoms. Patients with chronic obstructive pulmonary
      disease tended to score higher; otherwise no relationship was found between the
      STAI sumscore and type of chronic somatic disease, nor between the STAI sumscore
      and number of drugs in regular use. CONCLUSIONS: STAI proved feasible for use in
      the elderly. The scoring on the STAI is high in geriatric in-patients. Further
      studies are needed to clarify to what extent this relates to a high prevalence of
      anxiety disorders.

PMID- 11466746
TI  - The incidence of dementia in an Australian community population: the Sydney Older
      Persons Study.
AB  - OBJECTIVES: Limited Australian dementia incidence data are available. This study
      aimed to identify the incidence of dementia and its subtypes in an Australian
      community dwelling population. METHOD: A community dwelling sample of 647
      subjects aged > or =75 years at recruitment were followed for a mean period of
      3.2 years (range 2.6-4.5 years). The incidence of dementia (measured in person
      years at risk) was identified for different levels of severity of dementia,
      Alzheimer's disease and vascular dementia. RESULTS: Incidence figures were
      slightly higher than those previously reported. The incidence of dementia and of
      Alzheimer's disease increased with age but was not affected by gender. The
      incidence of vascular dementia was not affected by age. CONCLUSION: This study
      provides the largest body of data on the incidence of dementia in Australia,
      indicating a slightly higher incidence of dementia than previous reports. Further
      Australian data are required to confirm these findings.

PMID- 11466748
TI  - Clinically significant depressive symptoms and very mild to mild dementia of the
      Alzheimer type.
AB  - OBJECTIVE: To compare depressive symptoms reported by persons with very mild or
      mild dementia of the Alzheimer type (DAT) with those reported for the person by a
      collateral source. DESIGN: Cross-sectional evaluation. SETTING: Washington
      University Alzheimer's Disease Research Center. PARTICIPANTS: Consecutive series
      of elderly volunteers (n = 156) enrolled in longitudinal studies with a Clinical
      Dementia Rating (CDR) of 0.5 (very mild) or 1 (mild). Twenty-one per cent (n =
      33) exhibited clinically significant depressive symptoms for which treatment was
      recommended. MAIN OUTCOME MEASURES: Presence and frequency of DSM-IV depressive
      symptoms within the last year and last month reported by the participant or
      collateral source as ascertained by clinical examination and structured
      interviews. RESULTS: Collateral source information is essential in diagnosing
      clinically significant depressive symptoms. The Geriatric Depression Scale scores
      correlate with participant information only and therefore may substantially
      underestimate depression. Depressive symptoms fluctuate in individuals with DAT.
      The most consistent depressive symptoms are depressed mood, fatigue and
      indecision. CONCLUSIONS: Clinically significant depressive symptoms may be common
      in individuals with very mild or mild DAT, although they may fluctuate.
      Information from both a knowledgeable collateral source and the participant is
      important for detection of depressive symptoms.

PMID- 11466749
TI  - Secondary prevention of depressive symptoms in elderly inhabitants of residential
      homes.
AB  - The effects of a multifaceted secondary prevention intervention in residential
      homes in the Netherlands were examined, using a quasi-experimental design. In
      five experimental residential homes, the caregivers received three training
      sessions on detecting depression and on supporting depressed residents.
      Furthermore, an information session was organized for all personnel, a further
      session was organized for residents and their relatives, and several group
      interventions were offered. 213 residents participated in the study. 211
      residents of five other residential homes, matched on basic variables, served as
      a comparison group. Effects on depressive symptoms (geriatric depression scale)
      and health related quality of life (MOS-SF-36) were measured at pretest and after
      the intervention, one year later. Because the drop-out rate was high and drop
      outs differed significantly from the remaining population, the scores of drop
      outs were imputed. Since we used a quasi-experimental design, we controlled for
      confounding variables. Regression analyses resulted in significant effects of the
      intervention on the GDS and on role functioning in the total population. When the
      analyses were limited to those scoring high on the GDS at pretest, significant
      effects were found on the GDS, and on four domains of health-related quality of
      life: psychological distress, role functioning, pain and social functioning. The
      improvement in GDS scores in GDS cases was significantly larger than in other
      subjects. Our results suggest that general approaches aimed at a residential home
      are capable of influencing depressive symptoms in inhabitants. Possibly, it may
      not be necessary to wait until depressive symptoms have escalated and inhabitants
      need extensive treatment.

PMID- 11466750
TI  - An investigation of visual hallucinosis and visual sensory status in dementia.
AB  - INTRODUCTION: Visual hallucinosis occurs frequently amongst patients with
      dementia and there is some evidence of an association between hallucinosis and
      impaired visual function. This study examined the association between objectively
      rated visual acuity, ambient illumination levels and hallucinosis in patients
      with dementia. METHODS: Thirty dementia patients with visual hallucinosis plus 30
      non-hallucinating dementia patients were recruited from referrals to community
      mental health teams in Leicestershire. Data were collected by means of a carer
      interview (including the Neuro-Psychiatric Inventory (NPI) and Clinical Dementia
      Rating Scale (CDR)), patient assessment (including Mini-Mental State Examination
      (MMSE) and measures of corrected visual acuity) and photometric assessment of the
      room most frequently occupied by the subject. RESULTS: Hallucinators and non
      hallucinators did not differ significantly in respect of age, cognitive status or
      global dementia severity. Fifty per cent of hallucinators had a Snellen visual
      acuity of 6/24 or worse compared with 27% of non-hallucinators. Comparison of
      LogMAR transformed values for distance (Snellen chart) and near-vision (Sussex
      test-types) revealed significantly worse visual acuity for hallucinators on both
      measures (Mann-Whitney p < 0.05 and p < 0.01, respectively). Ambient illumination
      in the centre of the room under conditions of natural plus artificial lighting
      was significantly lower for hallucinating subjects than for non-hallucinators
      (median values 200 versus 345 Lux respectively; Mann-Whitney p < 0.05).
      CONCLUSION: These results are consistent with previous findings suggesting an
      association between visual hallucinations and poor visual acuity in patients with
      dementia, and introduce environmental illumination as another possible
      aetiologically relevant factor. Interventions aimed at improving visual function
      in this patient group now require evaluation.

PMID- 11466751
TI  - Guidelines for the management of agitation in dementia.

PMID- 11466752
TI  - Longitudinal follow-up of depressive symptoms among normal versus cognitively
      impaired elderly.
AB  - OBJECTIVES: This prospectively designed longitudinal study assesses prevalence,
      incidence and prognosis of depressive symptoms among cognitively normal elderly
      volunteers compared with patients with mild cognitive impairment (MCI), dementia
      of Alzheimer type (DAT), and vascular dementia (VAD). Possible relationships
      between depressive symptoms, cognitive performance, disease types, and effects of
      antidepressant treatment were analyzed. METHODS: Two hundred and ninety four
      subjects exhibiting different levels of cognitive performance were admitted to
      this study. Demographics, cardiovascular and neurodegenerative risk factors,
      together with measures of neuropsychological test performance, were obtained at
      sequential visits. Depressive symptoms were selectively treated with
      antidepressant medications. RESULTS: One hundred and forty six subjects with
      normal cognition, 19 subjects with MCI, 42 patients with DAT, and 32 patients
      with VAD were followed for a mean of 3.5 years. With the passage of time, there
      were trends showing prevalence of depressive symptoms to decrease among DAT and
      to increase among VAD patients. VAD patients exhibited the highest incidences of
      new-onset depressive symptoms, followed in incidence by DAT and MCI groups.
      Depressive symptoms among VAD and MCI patients were more persistent and
      refractory to antidepressant medications than for DAT patients. Trends suggested
      that antidepressant treatment might benefit MCI and VAD subjects more than DAT
      patients. Motivationally related depressive symptoms accounted for major
      components of elevated Hamilton depression rating scale scores. CONCLUSIONS:
      Depressive symptoms among DAT patients have higher rates of spontaneous
      resolution, without requiring intensive drug treatment, than among VAD patients
      in whom depressive symptoms are more persistent and refractory to drug treatment.
      Early depressive symptoms among subjects with MCI may represent a preclinical
      sign and should be considered as a risk factor for impending DAT or VAD among the
      elderly.

PMID- 11466753
TI  - Confidence of primary care physicians in assessing the suicidality of geriatric
      patients.
AB  - This study examined the confidence levels of physicians in assessing the risk of
      suicide among older adults in clinical settings. Of the 300 physicians who were
      selected from a population of 4980 family practice, internal medicine, and
      geriatric physicians in Illinois, 63% responded to the mail survey. Several
      categorical items inquired about specific assessment and treatment approaches,
      referral resources used, barriers to meeting the mental health needs of older
      patients, and sources of training in suicide risk assessment. All the training
      items (suicide assessment in medical school, residency, and CME courses; rating
      of medical school training; and insufficient training in geriatric mental health)
      were significantly (p < 0.01) associated with confidence in assessing
      suicidality. The overall model consisting of six variables explained 57% of the
      variation in confidence scores [F (6, 130) = 28.48, p < 0.001]. Three variables
      accounted for 50% of the explained variance: confidence in diagnosing depression,
      residency training in the assessment of suicide risk, and assessment of the
      intentional misuse of medication. Confidence in diagnosing depression (beta =
      0.38, p < 0.001) was the strongest predictor. More effective mental health care
      will require specific preparation in treating geriatric patients through the full
      spectrum of medical training, including medical school, residency, and CME
      courses. Improved prevention of elderly suicide hinges on the enhancement of
      clinical skills in diagnosing and treating geriatric depression.

PMID- 11466754
TI  - Correlation between clock-drawing test and paranoid and delusional ideation in
      dementia of the Alzheimer's type.

PMID- 11466755
TI  - Current awareness in geriatric psychiatry.

PMID- 11466757
TI  - Enantioselectivity of the musk odor sensation.
AB  - This brief review, the summary of a talk at the Symposium on Biological Chirality
      2000 in Szeged, Hungary, illustrates what chiral recognition tells us about the
      molecular parameters of the musk odor sensation. While the enantioselectivity of
      odor perception is strong evidence for the key role of proteinogenic receptors in
      the molecular mechanism of olfaction, the quantitative and qualitative odor
      differences of enantiomers are often not very pronounced, as in the case of
      muscone (17/26). In those cases, however, where there is strong
      enantiodiscrimination, we find most intense musk odorants with very low odor
      thresholds, such as (-)-(12R)-12-methyl-9-oxa-14-tetradecanolide (35), (12R;9Z)
      12-methyl-14-tetradec-9-enolide [(R)-Nirvanolide, 38], and (-)-(4S;7R)
      1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran [(-)
      (4S;7R)-Galaxolide, 57], the latter being rather rigid. We thus can assume the
      geometry of the musk receptor to be fairly complementary to these compounds,
      which therefore can serve as templates for the design of new musk odorants.

PMID- 11466758
TI  - Chirality and symmetry aspects of spheroarenes, including fullerenes.
AB  - The design of the smallest spheroarenes (C(N) molecules based on trivalent
      polyhedral framework, a class which subsumes fullerenes) of any point-group
      symmetry is presented. The role of Curie's principle is discussed. Some molecules
      whose carbon backbone is a nonplanar graph are described.

PMID- 11466759
TI  - Determination of enantiomerization barriers by dynamic and stopped-flow
      chromatographic methods.
AB  - In recent years, dynamic chromatography and stopped-flow chromatographic
      techniques have become versatile tools for the determination of enantiomerization
      and isomerization barriers. Increasing demands for the stereochemical safety of
      chiral drugs contributed to the rapid development of new techniques. New computer
      aided evaluation systems allow the on-line determination of interconversion
      barriers from the experimental chromatograms. Both dynamic chromatography and
      stopped-flow chromatography have been applied to the entire range of
      chromatographic methods (GC, SFC, HPLC, CE).

PMID- 11466760
TI  - Variable stereochemistry in highly branched isoprenoids from diatoms.
AB  - C(25) highly branched isoprenoid (HBI) alkenes are ubiquitous lipids found in
      geochemical samples around the globe. The origins of these widespread
      geochemicals are believed to be restricted to a limited number of diatoms,
      including Haslea ostrearia (and related species), Rhizosolenia setigera, and
      Pleurosigma intermedium. The unsaturation of the HBI alkenes ranges from 2-6 in
      different species and cultures. The number of stereogenic centres is usually
      limited to two in the HBI alkenes due to double bond positions. The relative
      and/or absolute configurations for these have been determined for a range of HBI
      alkenes produced from different diatoms cultured under a number of growth
      conditions. These determinations have involved a combined spectroscopic and
      chromatographic analysis using NMR spectroscopy and chiral gas chromatography,
      respectively. HBIs isolated from Haslea spp. belong to a specific structural type
      which exhibit configurational diastereoisomerism, while those isolated from P.
      intermedium and R. setigera represent a different structural type and usually
      exist as mixtures of geometric isomers only. HBIs are reported from a new species
      of diatom whose stereochemical properties lie between those found for Haslea spp.
      and P. intermedium.

PMID- 11466761
TI  - Narcotic drug methohexital: synthesis by enantioselective catalysis.
AB  - The narcotic drug methohexital 1 contains two asymmetric carbon atoms and, thus,
      consists of four isomers, two diastereomeric pairs of enantiomers. The commercial
      drug is the so-called alpha-racemate, one pair of diastereomers only. A method
      was developed to prepare differently enriched mixtures of methohexital isomers
      without resorting to lengthy and expensive optical resolutions. A model reaction
      for the synthesis of methohexital is the palladium-catalyzed allylation of 1,5
      dimethyl-barbituric acid 3, which is optimized and checked by molecular modeling.
      Catalysts with the best ligands are used in the allylation of the methohexital
      precursor 7, which contains the C(6) sidechain at the tetrahedral center of the
      barbiturate skeleton. The product stereochemistry was determined by the
      contribution of the enantioselective Pd catalysts and by the fact that the
      allylation is a kinetic resolution. The methohexital isomer mixtures obtained
      were evaluated with the corneal stimulus test of rats. Methohexital compositions
      were found, which are superior to the commercially used alpha-racemate
      (Brevimytal).

PMID- 11466762
TI  - Formation of highly enantioenriched microenvironments by stochastic sorting of
      conglomerate crystals: a plausible mechanism for generation of enantioenrichment
      on the prebiotic earth.
AB  - Abiotic generation of local areas of enantioenrichment is to be expected whenever
      one deals with the 5-10% of organic solids that crystallize as conglomerates.
      Since an individual crystal of a conglomerate contains only a single enantiomer,
      simple sorting processes involving winds, waves, or similar forces can act to
      deposit individual crystals into unique environments. Subsequent dissolution may
      afford nearly enantiopure solutions. Therefore, in contrast to common perception,
      enantioenrichment is not a unique signature of living systems, it is simply
      evidence of a certain degree of chemical complexity.

PMID- 11466763
TI  - Solvent-free optical resolution of N-methylamphetamine by distillation after
      partial diastereoisomeric salt formation.
AB  - Solvent-free optical resolution of N-methylamphetamine was developed by
      distillation after partial diastereoisomeric salt formation. From the 18 chiral
      acids tested by this method, five provide by this method resolution: O,O'
      dibenzoyltartaric acid, O,O'-di-p-toluoyltartaric acid, 6-methoxy-alpha-methyl-2
      naphthaleneacetic acid (Naproxen), the cis-permetrinic acid, and the 2
      phenoxypropionic acid. Among them the O,O'-dibenzoyltartaric acid in water-free
      form provided the more effective resolution. The efficiency of this resolution S
      = 0.74 is in the range of the industrial-scale resolutions and not worse than the
      efficiency achieved by optical resolution via fractional crystallization.

PMID- 11466764
TI  - Development of an improved automated gas-chromatographic chiral analysis system:
      application to non-natural amino acids and natural protein hydrolysates.
AB  - In the use of combinatorial chemistry as a novel strategy for drug discovery, the
      chirality assessment of building blocks used for library construction is
      particularly important in the evaluation of biological actions of generated
      libraries. The procedure for chiral analysis of lead compounds in screening may
      be of a high priority, particularly in the case of the protection of intellectual
      rights. Previously, an automated amino acid analysis system using enantiomer
      labeling was developed. The system incorporates a reactor, which allows automated
      esterification and acylation of amino acids, and is connected to an on-line gas
      chromatographic system. A capillary column coated with a chiral phase is employed
      for the separation of the enantiomers. This particular system is improved with a
      newly constructed "high-throughput auto-derivatizer" in combination with a new GC
      system. The resulting data can be processed by newly constructed software. The
      analyses of amino acid derivatives or hydrolysates of proteins and peptides are
      carried out routinely within ca. 45 min, including derivatization. Using this
      system several non-natural amino acids were tested with respect to the
      stereoisomeric configuration. In addition, acid hydrolysates of food proteins and
      tissues obtained by autopsy were analyzed as an application to proteome research.

PMID- 11466765
TI  - Conditions for chiral asymmetry generation in the preparation of the chiral
      octahedral cobalt complex.
AB  - We have reported that the random chiral asymmetry generation, which is a
      spontaneous preferential generation of one enantiomer, was observed in the
      synthesis of a chiral octahedral cobalt complex, cis-[CoBr(NH(3))(en)(2)]Br(2).
      In this article, we review our studies to explain in this system the
      autocatalytic growth of small enantiomeric excess that arises due to statistical
      fluctuations. One important experimental finding was that the rate of chiral
      autocatalysis increased with increasing the degree of supersaturation.
      Furthermore, our numerical simulation indicates that even small inhomogeneities
      in the reaction system may play a significant role because their effect is
      amplified by the autocatalytic reaction under appropriate conditions. In a small
      volume, fluctuations in concentration can grow if the autocatalytic growth
      overcomes the diffusional loss of the excess concentration from this volume. This
      may makes the enantiomeric excess of the chiral complex randomly fluctuate from
      run to run.

PMID- 11466766
TI  - Some applications of a chiral fluorometric reagent, (S)-TBMB carboxylic acid.
AB  - Molecular design and applications of a fluorometric chiral agent, (S)-TBMB
      carboxylic acid, are briefly reviewed. The agent, possessing an asymmetric 1,3
      benzodioxole skeleton, was designed as a novel class of chiral agent that
      functions also as a benzoate chromophore for exciton chirality CD methods. The
      utility of this agent has been demonstrated in an application to determine
      enantiomeric amino acids, acyl-sn-glycerols, glycosyl-sn-glycerols, and other
      chiral alcohols and amines.

PMID- 11466767
TI  - Chiral detection of carotenoid assemblies.
AB  - Carotenoid assemblies were produced by aqueous dilution of ethanolic solutions.
      UV/VIS and CD spectroscopy revealed the formation of J- and H-types of aggregates
      of both right- and left-handed kinds. Simulation of UV/VIS spectra of the
      aggregates showed characteristic differences between the two types. 6'-Epimers of
      capsanthol ((all-E,3R,3'S,5'R)-beta,kappa-carotene-3,3',6'-triols) formed
      assemblies with increased chirality in dilute solution. While the absorption of
      6'R-capsanthol giving H-type aggregate does not depend on the concentration, 6'S
      capsanthol yielding J-type assembly showed concentration-dependent absorption
      intensity. Dilute aggregate of 6'R-capsanthol is characterized by an extremely
      large A value of -6,600. The transformation of J- to H-type assembly was observed
      in the mixtures of the epimers producing an intermediate kind of aggregate. A
      hypothetical structure for H-type assemblies is proposed.

PMID- 11466768
TI  - Enantiomer separation of hydrocarbons in preparation for ROSETTA's "chirality
      experiment".
AB  - Until now the favored method for separating racemic pairs of underivatized
      alcohols, diols, and phenylsubstituted amines has been gas chromatography on
      cyclodextrin phases. However, certain enantiomers of saturated chiral
      hydrocarbons could not be resolved in this way because they lack the functional
      groups necessary to undergo "intensive" diastereomeric interactions with the
      cyclodextrins. The present study describes a gas-chromatographic technique for
      resolution of saturated aliphatic hydrocarbons into their enantiomers and
      presents a brief discussion of the possible applications. The (enantiomer)
      separations were performed in preparation for the Cometary Sampling and
      Composition Experiment on board the cometary lander RoLand, part of ESA's
      cornerstone mission ROSETTA. This experiment has been designed to investigate the
      hypotheses that biomolecular asymmetry has an interstellar origin and to separate
      and identify a wide range of organic enantiomers in situ on the surface of a
      comet's nucleus.

PMID- 11466769
TI  - Carbohydrate-derived alkylcobalt carbonyl:([(1,2:5,6-di-O,O-isopropylidene-alpha
      D-glucofuranos-3-yl)oxycarbonyl]methyl)cobalt tricarbonyl triphenylphosphene.
AB  - A carbohydrate-derivative alkylcobalt carbonyl,([(1,2:5,6-di-O,O-isopropylidene
      alpha-D-glucofuranos-3-yl)oxycarbonyl]methyl)cobalt tricarbonyl
      triphenylphosphene(3) was prepared and characterized by IR, NMR, and CD spectra,
      as well as by X-ray diffraction. The supramolecular chemistry in the crystalline
      P2(1)2(1)2(1) (chiral) phase and in solution was analyzed and compared. The bulky
      carbohydrate-based ligand stabilized one chiral conformation, which, however, is
      less ordered than for analogous compounds with more flexible and less bulky
      chiral groups. Intermolecular, H-bond interactions are more important in the
      P2(1)2(1)2(1) phase of complex 3 than at other analogous compounds.

PMID- 11466770
TI  - Nonhanded chirality in octahedral metal complexes.
AB  - Chiral molecules can either be handed (i.e., "shoes") or nonhanded ("potatoes").
      The only chiral ligand partition for tetrahedral metal complexes (or for a
      tetrahedral carbon atom such as that found in amino acids and other chiral
      biological molecules) is the fully unsymmetrical degree 6 partition (1(4)), which
      leads to handed metal complexes of the type MABCD with a lowest-degree chirality
      polynomial consisting of the product of all six possible linear factors of the
      type (s(i)-s(j)) where 1 < or = i,j < or = 4. The lowest-degree chiral ligand
      partitions for octahedral metal complexes are the degree 6 partitions (31(3)) and
      (2(3)) leading to handed chiral metal complexes of the types fac-MA(3)BCD and cis
      MA(2)B(2)C(2). The form of the lowest-degree chirality polynomial for the (31(3))
      chiral ligand partition of the octahedron resembles that of the (1(4)) chiral
      ligand partition of the tetrahedron, likewise with four different ligands.
      However, the form of the lowest-degree chirality polynomial for the (2(3)) chiral
      ligand partition of the octahedron corresponds to the square of the chirality
      polynomial of the (1(3)) chiral ligand partition of the polarized triangle, which
      likewise has three different ligands. Ligand partitions for octahedral metal
      complexes such as (2(2)1(2)), (21(4)), and (1(6)), which are less symmetrical
      than the lowest-degree chiral ligand partitions (31(3)) and (2(3)), lead to
      chiral octahedral metal complexes which are nonhanded. In such complexes, pairs
      of enantiomers can be interconverted by simple ligand interchanges without ever
      going through an achiral intermediate.

PMID- 11466771
TI  - Chiral recognition of dipeptide methyl esters by an anionic beta-cyclodextrin.
AB  - Chiral recognition of dipeptide methyl esters by anionic heptakis[6
      carboxymethylthio-6-deoxy]-beta-cyclodextrin (per-CO(2)(-)-beta-CD) was studied
      in D(2)O at pD 7.0 by means of (1)H NMR spectroscopy. The methyl esters of
      alanylalanine (Ala-Ala-OMe), alanylleucine (Ala-Leu-OMe), alanyltryptophan (Ala
      Trp-OMe), glycyltryptophan (Gly-Trp-OMe), valyltryptophan (Val-Trp-OMe),
      leucyltryptophan (Leu-Trp-OMe), and tryptophylalanine (Trp-Ala-OMe) were used as
      the dipeptides. The binding constant (K) determined from NMR titration increases
      in the order Ala-Ala-OMe < Ala-Leu-OMe < Ala-Trp-OMe, suggesting that van der
      Waals interactions between the host and the guest participate in complexation.
      Coulomb interactions between the protonated dipeptide methyl esters and the
      anionic host seem to be another attractive force. Per-CO(2)(-)-beta-CD interacts
      with the (R,R)-enantiomers of the dipeptide methyl esters more strongly than the
      (S,S)-enantiomers. Such enantioselectivity corresponds to that for alpha-amino
      acid methyl esters such as Leu-OMe and Trp-OMe, whose (R)-enantiomers are the
      preferable guests. The enantioselectivity is mainly dominated by amino acid
      residue at the C-terminal and chirality at the N-terminal residue plays an
      assistant role. An asymmetrically twisted shape of the host cavity may be
      essential for chiral recognition.

PMID- 11466772
TI  - Why are the terpenoid indole alkaloids of type I homochiral?
AB  - In the presence of the enzyme strictosidine synthase, the coupling reaction of
      secologanin and tryptamine is completely stereoselective and affords
      strictosidine with 3S configuration, exclusively. The stereoselectivity is
      transferred and retained in most indole alkaloids of type I in which C-3 is not
      involved in subsequent reactions. By using results of model reactions, the
      stereoselectivity was interpreted by the bulkiness of the enzyme temporarily
      attached to the N-4 atom in the formation of the indolenine intermediate. 3S
      configuration is kept in the subsequent 1,2-rearrangement into the beta-carboline
      structure. In the formation of the oxindole derivatives, the 3S configuration is
      preferred, but not necessarily complete.

PMID- 11466773
TI  - Enantioconvergent synthesis of (-)-(S)- and (+)-(R)-2-acetyl-3,6
      dihydroxycyclohex-2-enone starting from rac-6-hydroxy-3-methoxycyclohex-2-enone.
AB  - The synthesis of enantiomerically pure (-)-(S)- and (+)-(R)-2-acyl-3,6
      dihydroxycyclohex-2-enone starting from diastereomerically pure N-tosyl-(S)
      proline esters 3-methoxy-6-hydroxycyclohex-2-enone 1 is presented. An
      enantioconvergent synthesis of either (-)-(S)- and (+)-(R)-2-acyl-3,6
      dihydroxycyclohex-2-enone starting with the racemic alpha-ketol 1 through a
      conversion of ( approximately 1:1) mixture of diastereomeric esters into one
      diastereomer by a repeated crystallization, followed by dimethylaminopyridine
      catalyzed equilibration as key steps is described.

PMID- 11466774
TI  - Chiroptical properties of 2,3-dihydrobenzo[b]furan and chromane chromophores in
      naturally occurring O-heterocycles.
AB  - The correlation between the helicity (absolute conformation) of the O
      heterocyclic ring of chiral 2,3-dihydrobenzo[b]furan (1) and chromane (2)
      derivatives and their (1)L(b) band CD was investigated. The same helicity rule
      was found for both unsubstituted chromophores: P/M helicity of the heterocyclic
      ring leads to a negative/positive CD within the (1)L(b) band. While the
      substitution of the fused benzene ring by achiral substituents does not change
      this helicity rule for the chromane chromophore, it leads to its inversion for
      the 2,3-dihydrobenzo[b]furan chromophores. On the basis of these observations,
      the published absolute configurations of natural flavonol and pterocarpan
      derivatives were confirmed and the configurational assignments of several natural
      neolignans revised.

PMID- 11466775
TI  - Catalyzed asymmetric dialkylzinc addition to benzaldehyde in the presence of new
      chiral ligands--delta-(1-phenethyl)aminoalcohols.
AB  - A series of delta-aminoalcohols prepared from (S)- and (R)-N,N-dimethyl-1
      phenethylamines was found to catalyze the enantioselective addition of
      diethylzinc to benzaldehyde to yield optically active 1-phenylpropanol with
      enantiomeric excess 60-85%.

PMID- 11466776
TI  - Kerogen-bound and free hopanoic acids in the messel oil shale kerogen.
AB  - The distribution of the free and bound hopanoic acids in both unheated and heated
      (350 degrees C for 50 h) kerogens, isolated from the Messel oil shale, were
      analyzed by GC-MS. The bound acids were released by subjecting the kerogen to
      three different treatments, namely, thermochemolysis in the presence of
      tetramethylammonium hydroxide (TMAH), as well as basic and acidic hydrolyses. All
      of these methods gave a series of hopanoic acids ranging from C(30) to C(34), in
      which the biological 17beta, 21beta(H) configuration is prominent. Both 22R and
      22S epimers are present for the C(30) acid, whereas the others are dominated by
      the sidechain 22R-configuration. Thermochemolysis in the presence of TMAH was the
      most efficient in releasing kerogen-bound hopanoids. Following pyrolysis, the
      acids are generated and released into the free fraction with apparent
      epimerization occurring at C-17, C-21, and C-22. The bound hopanoic acids may be
      both chemically bonded as well as possibly being physically encapsulated within
      the macromolecular fraction of sedimentary organic matter. They are therefore
      either generated by breaking the bonds which bind them to the kerogen or they are
      released as a result of the macromolecular cage being broken apart.

PMID- 11466777
TI  - Geochemical evolution of amino acids in dentine of Pleistocene bears.
AB  - A linear correlation was established between aspartic acid racemization ratio
      from cave bear dentine collagen and absolute dating. The high correlation
      coefficient obtained allowed age calculation through amino acid racemization.
      Aspartic acid and glutamic acid racemization kinetics have also been explored in
      dentine from a North American black bear (Ursus americanus Pallas). Three sample
      sets were prepared for kinetic heating experiments in nitrogen atmosphere: one
      water soaked, one with a water-saturated nitrogen atmosphere, and one without any
      moisture. It was possible to show that the presence of water is a factor
      controlling amino acid racemization rate. The aspartic acid in a heating
      experiment at 105 degrees C shows an "apparent kinetics reversal" which can be
      explained by a progressive hydrolysis of amino acid chains (proteins and
      polypeptides). Because of the low potential of collagen preservation over long
      periods of time, the apparent kinetics reversal phenomenon will not affect the
      dating of old material where no traces of collagen remain. An apparent kinetics
      reversal was not observed in glutamic acid, which racemizates more slowly.

PMID- 11466780
TI  - Natural intramolecular isotope measurements in physiology: elements of the case
      for an effort toward high-precision position-specific isotope analysis.
AB  - Chemical information available in organisms can be categorized into three major
      domains, macromolecular, small molecules, and isotope ratios. Information about
      physiological state is commonly obtained by qualitative and quantitative analysis
      in the macromolecular and small molecule domains. Genomics and proteomics are
      emerging approaches to analysis of macromolecules, and both areas yield
      definitive information on present physiological state. There is relatively little
      record of past physiological states of the individual available in these domains.
      Natural isotopic variability, particularly on an intramolecular level, is likely
      to retain more physiological history. Because of ubiquitous isotopic
      fractionation, every stereochemically unique position in every molecule has an
      isotope ratio that reflects the processes of synthesis and degradation. This fact
      highlights a vast amount of organismal chemical information that is essentially
      unstudied. Isotope measurements can be classified according to the chemical
      complexity of the analyte into bulk, compound-specific, and position-specific or
      intramolecular levels. Recent advances in analysis of isotope ratios are
      transforming natural science, and particularly answering questions about
      ecosystems using bulk methods; however, they have had relatively little impact on
      physiology. This may be because the vast complexities of physiological questions
      demand very selective information available in position-specific isotope analysis
      (PSIA). The relatively few high-precision PSIA studies, based on isotope ratio
      mass spectrometry (IRMS), have revealed intramolecular isotope ratio differences
      in pivotal physiological compounds including amino acids, glucose, glycerol,
      acetate, fatty acids, and purines. The majority of these analyses have been
      accomplished by laborious offline methods; however, recent advances in
      instrumentation presage rapid PSIA that will be necessary to attack real
      physiological problems. Gas-phase pyrolysis has been shown to be an effective
      method to determine (13)C/(12)C at high precision for molecular fragments, and
      technologies to extend C-based PSIA to N and other organic elements are emerging.
      Two related efforts are warranted, (a) development of rapid, convenient, and
      sensitive methods for high-precision PSIA, a necessary precursor to (b) a
      concerted investigation into the relationship of metabolic state to
      intramolecular isotope ratio. Inherent in this latter goal is the need to
      identify long-lived molecules in long-lived cells that retain a record of early
      isotopic conditions, as has been shown for post-mortem human neuronal DNA. Using
      known metabolic precursor-product relationships between intramolecular positions,
      future studies of physiological isotope fractionation should reveal the
      relationship of diet and environment to observed isotope ratio. This science of
      isotope physiology, or simply isotopics, should add an important tool for
      elucidation of early factors that effect later health, probably the most
      difficult class of biomedical issues.

PMID- 11466781
TI  - Diurnal fluxes and the isotopomer ratios of N(2)O in a temperate grassland
      following urine amendment.
AB  - There is an urgent need to provide an accurate, up-to-date estimate of N(2)O
      fluxes in order that national policies can be developed to reduce emissions of
      N(2)O from soils. There are only limited data on temporal and diurnal patterns of
      N(2)O fluxes to the atmosphere, mainly due to constraints in the measurement
      techniques. In this paper we present the first terrestrial source values of N(2)O
      isotopomers and have measured and quantified the temporal and diurnal variability
      in N(2)O fluxes following urine addition to a grassland system in the UK. The
      experiment was carried out over a 2-week period on an artificially drained
      grassland system at the Institute of Grassland and Environmental Research (IGER),
      North Wyke, UK. Duplicate samples of urine, each of 2 L, were collected from
      dairy cows and applied to chambers (of area 0.16 m(2)). The N(2)O diurnal fluxes
      from urine and control (no urine) plots were measured by an automatic closed
      chamber technique. The isotopomers of N(2)O were obtained by analysing the gas
      samples collected during a peak emission phase. Soil and meteorological data were
      also collected. The results showed strong diurnal variations in N(2)O fluxes with
      minimum fluxes generally occurring between 7:00 and 14:00 hrs. The total
      cumulative flux of N(2)O for the whole experimental period was higher by a factor
      of >2 compared with estimates based on the daytime (between 10.00-16.00 hrs)
      measurements only. Therefore, measurements of N(2)O fluxes based on daily single
      exposure and expressed on a 24-h basis could impose a considerable bias and
      inaccuracy to the emission estimates, depending on when it was taken. The
      measured site preference values (difference between the centre (delta(15)Nalpha)
      and the end (delta(15)Nbeta) N atom of the N(2)O molecule) for soil-emitted N(2)O
      measured during our study were always lower than the tropospheric value. This
      work confirms that the enhanced tropospheric N(2)O site preference value could be
      the result of the back injection from the stratosphere. The intramolecular
      isotope ratios of nitrogen (delta(15)N) and oxygen (delta(18)O) and the site
      preference of the emitted N(2)O indicated that there was a shift of processes
      during the measurement period.

PMID- 11466782
TI  - Stable isotopes and the international system of units.
AB  - It is now over 60 years since Nier built the first isotope ratio mass
      spectrometer. The introduction of continuous-flow techniques heralded a huge
      expansion in the use of stable isotopes in biomedical and environmental sciences,
      yet there is no consensus on the appropriate units, especially in the biomedical
      field. Most isotope ratio mass spectrometry (IRMS) instruments calculate isotopic
      abundance in terms of delta notation (delta, per thousand, per mil), which is a
      convention determined by geochemistry, because most of the original IRMS
      instruments were developed in isotope geochemistry laboratories to measure
      natural abundance variations. Delta units are not SI units. This paper considers
      the appropriate units for studies using stable isotopes based on the
      International System of Units (SI). The SI base unit for concentration is the
      mol, from which atom fraction and mol fraction are derived. The units of stable
      isotope abundance, atom % and mol %, are the atom and mol fractions expressed as
      percentages. Atom % excess and mol % excess are the SI units of enrichment and
      are to be recommended for use in tracer studies.

PMID- 11466783
TI  - Development of delta(15)N stratification of NO(3)(-) in soil profiles.
AB  - New evidence, obtained using a robust method for measuring the delta(15)N of
      NO(3)(-)-N in soil, is consistent with denitrification being the major
      determinant in the vertical distribution of NO(3)(-)-delta(15)N in soil profiles.
      These data also suggest that varying moisture regimes result in different effects
      of soil NO(3)(-)-N leaching on residual whole soil delta(15)N.

PMID- 11466784
TI  - Rapid quality control analysis of (13)C-enriched substrate synthesis by isotope
      ratio mass spectrometry.
AB  - There is a growing interest in the use of (13)C-enriched substrates to
      investigate metabolic processes in humans. The non-invasive nature of (13)C
      breath tests makes them attractive to clinicians, particularly because they can
      be safely used in children. The availability of suitable (13)C-enriched
      substrates can limit the application of this biotechnology. We have used isotope
      ratio mass spectrometry to assay the chemical purity and isotopic enrichment of
      substrates that were synthesised to study gut transit and colonic fermentation.
      Lactose ureide and lactose [(13)C]ureide were synthesised by acid-catalysed
      condensation of lactose and urea or (13)C urea, respectively. Glucose ureide and
      glucose [(13)C]ureide were synthesised by similar methods but required an
      additional purification step to remove urea of crystallisation. Substrates were
      analysed by standard analytical techniques and combustion isotope ratio mass
      spectrometry for carbon and nitrogen content and (13)C-enrichment. Monitoring the
      C/N ratio proved to be a sensitive assay of chemical purity. Analysis of the
      percentage composition of C and N (and hence O + H) suggested that lactose ureide
      crystallises as the dihydrate. It was synthesised with approximately 99% chemical
      purity and with the theoretical enrichment. Glucose ureide was synthesised with
      approximately 98% chemical purity but with lower than theoretical enrichment.

PMID- 11466785
TI  - Deuterium/hydrogen isotope ratio measurement of water and organic samples by
      continuous-flow isotope ratio mass spectrometry using chromium as the reducing
      agent in an elemental analyser.
AB  - A rapid continuous-flow technique for quantitative determination of hydrogen
      isotope ratios in water and organic materials at natural abundance levels is
      described. Water and organic samples were reduced in a helium stream at
      temperatures in excess of 1000 degrees C over chromium metal. delta(2)H per
      thousand values of water and organic samples were determined by calibration
      against International Atomic Energy Agency reference materials V-SMOW and SLAP
      water. The accuracy of the method was demonstrated through the analysis of the
      intermediate water standard GISP and IAEA water intercomparison materials OH-1,
      OH-2 and OH-3. Values obtained using this technique compared well with reference
      values (maximum difference 2.2 per thousand). The precision of water analyses was
      less than 2.3 per thousand (1 sigma or 1 standard deviation) in all cases. No
      apparent memory effect was observed when measuring samples at the natural
      abundance level. The application of the technique to organic molecules and the
      salts of organic acids was successfully demonstrated by measuring the delta(2)H
      per thousand values of an n-hexadecane laboratory reference and anhydrous calcium
      formate versus water calibration materials.

PMID- 11466786
TI  - Characterisation of dissolved combined amino acids in marine waters.
AB  - Dissolved combined amino acids (DCAA) are important constituents of the dissolved
      organic nitrogen (DON) pool in marine environments, although little is known
      about their sources, dynamics and sinks. The DCAA pool consists of various
      compounds including proteins and peptides, proteins linked to sugars and amino
      acids adsorbed to humic and fulvic acids, clays and other materials. The
      proportions of each of these components and the extent to which they are used by
      microplankton living within the photic zone are not known. An investigation was
      carried out, using (15)N isotope dilution techniques, to determine the
      concentration and composition of dissolved amino acid pools in the marine
      environment. A near-shore seawater sample was collected and split into fractions
      to determine the concentrations of dissolved free amino acids (DFAA), DCAA and a
      <3 kDa dissolved peptide fraction (DPEP; obtained by ultrafiltration). DCAA and
      DPEP fractions were hydrolysed to yield free amino acids and all samples were
      analysed by gas chromatography/mass spectrometry (GC/MS) as
      isobutyloxycarbonyl/tert-butyldimethylsilyl derivatives. The DFAA was the
      smallest fraction representing approximately 1% of total dissolved amino acids.
      The majority of DCAA was contained in the low molecular weight DPEP fraction
      (90%) and was probably as a result of release from phytoplankton and degradation
      by heterotrophic bacteria.

PMID- 11466787
TI  - Use of a novel nitrification inhibitor to reduce nitrous oxide emission from
      (15)N-labelled dairy slurry injected into soil.
AB  - Recent recommendations for environmentally sound use of liquid animal manure
      often include injection of slurry into soil. Two of the most important undesired
      side effects, ammonia (NH(3)) volatilisation and odour emissions, are usually
      significantly reduced by slurry injection. On the other hand, because of the
      higher amount of nitrogen (N) remaining in soil, the risk of nitrate (NO(3)(-))
      leaching and nitrous oxide (N(2)O) emissions is increased. Thus, the reduction of
      local effects caused by NH(3) deposition, e.g. N enrichment and soil
      acidification, may be at the cost of large-scale effects such as ozone depletion
      and global warming as a result of emitted N(2)O. In this context, nitrification
      inhibitors can contribute significantly to a reduction in NO(3)(-) leaching and
      N(2)O production. A field experiment was carried out at IGER, North Wyke, which
      aimed to evaluate the effect of the new nitrification inhibitor 3,4
      dimethylpyrazole phosphate (DMPP/ENTEC). For this experiment, (15)N enriched
      dairy slurry was used and the isotopic label in soil N as well as in N(2)O were
      studied. After slurry injection into the grassland soil in August 2000, the major
      emissions of N(2)O occurred during the first ten days. As expected, high N(2)O
      emission rates and (15)N content of the emissions were concentrated on the slurry
      injection slots, showing a steep decrease towards the untreated centre-point
      between slurry injection slots. The nitrification inhibitor DMPP proved to be
      very efficient in reducing N(2)O emissions. At a rate of 2 kg DMPP ha(-1), the
      total amount of N(2)O emitted was reduced by 32%, when compared with slurry
      injection without DMPP. The isotopic label of the emitted N(2)O showed that
      during the 22-day experimental period, emissions from the slurry N pool were
      strongly reduced by DMPP from 0.93 kg N(2)O-N ha(-1) (-DMPP) to 0.50 kg N(2)O-N
      ha(-1) (+DMPP), while only a minor effect on emissions from the soil N pool was
      observed (0.69 to 0.60 kg N(2)O-N ha(-1); -DMPP, +DMPP, respectively).

PMID- 11466788
TI  - Hydrogen isotope analysis of natural abundance and deuterium-enriched waters by
      reduction over chromium on-line to a dynamic dual inlet isotope-ratio mass
      spectrometer.
AB  - This paper describes the application of a simple chromium reduction furnace which
      can be interfaced with a dual inlet isotope-ratio mass spectrometer thus
      providing the capacity for cheap, fast, accurate and precise measurement of
      deltaD(V-SMOW) by dynamic mass spectrometry. Measurements are precise to the
      order of < or =0.5 per thousand. Mean 95% confidence intervals for the Vienna
      Standard Mean Ocean Water (V-SMOW) to Standard Light Antarctic Precipitation
      (SLAP) range are in the order of 2.5 per thousand and the system is linear over
      the range -428 to 23,000 per thousand. Memory effects do exist, but are small for
      natural abundance samples and can be minimised by careful planning of the
      analytical load.

PMID- 11466789
TI  - The search for charge-remote reactions of even-electron anions derived from 1,3
      disubstituted adamantanes in the gas phase. Retro Diels-Alder and Norrish II
      processes.
AB  - The collision induced decompositions of 3-substituted adamantane carboxylate
      anions have been studied with a view to uncovering charge-remote fragmentations
      of the 3-substituent. The 3-substituent is chosen so that it cannot approach the
      anion site, and so any fragmentations of that substituent should proceed
      independently of the charged centre, viz. charge-remote reactions. The following
      systems have been studied (i) the 3-cyclohexenyl system shows no charge-remote
      retro Diels-Alder fragmentation (DeltaH = +157 kJ mol(-1)), instead, charge
      remote loss of the cyclohexenyl radical is noted, (ii) the 3-isobutyl ketone
      system shows no Norrish II cleavage (loss of C(3)H(6), DeltaH = +18 kJ mol(-1)),
      instead, the competitive losses of CO(2) from the charged carboxyl centre,
      together with charge-remote radical loss of the 3-substituent are observed, and
      (iii) the corresponding 3-isopropyl ester does show the "Norrish II" loss of
      C(3)H(6), together with competitive losses of CO(2) and the 3-substituent. It is
      concluded for cases (ii) and (iii), that an adamantane carboxylate anion system
      with a carbonyl group directly attached at the 3-position is not a suitable model
      system for studying charge-remote reactions.

PMID- 11466790
TI  - Selective self-ion/molecule reactions in both external and internal source ion
      trap mass spectrometers.
AB  - Novel results on the selective self-ion/molecule reactions (SSIMR) in both
      external and internal source ion trap mass spectrometers are demonstrated.
      Selective self-ion/molecule reaction product ions were produced between the
      oxygenated and nitrogenated crown ethers. For the oxygenated crown ethers, self
      ion/molecule reactions lead to the formation of the protonated ions, adduct ions
      of fragments ([M + F](+)) and [M + H(3)O](+), while the nitrogenated crown ethers
      produce [M + H](+), [M + CH](+) and [M + C(2)H(3)](+) ions.

PMID- 11466791
TI  - Reactions of first-row transition metal ions with propargyl alcohol in the gas
      phase.
AB  - The gas-phase reactions with propargyl alcohol (PPA) of all the singly charged
      ions of the first-row transition metals, generated by laser ablation in an
      external ion source, were studied by Fourier transform ion cyclotron resonance
      mass spectrometry (FT-ICRMS.). The reactivities of the metal ions change
      irregularly across the periodic table, and the reactivity of each ion is a
      function of its electronic configuration and corresponding metal-oxygen (M-O)
      bond energies. The 10 metal ions were classified into three categories according
      to their reactivities: Sc(+), Ti(+) and V(+) are the most reactive ions which
      react with PPA to give many kinds of oxygen-rich products due to stronger M-O
      bonds; Fe(+), Co(+) and Ni(+) are less reactive; Cr(+), Mn(+), Cu(+) and Zn(+)
      are the most unreactive ions, due to the half and completely occupied valence
      electronic configurations. The order of reactivity is Ti(+) > V(+) > Sc(+) >>
      Co(+) > Fe(+) approximately Ni(+) > Zn(+) > Cr(+) approximately Mn(+)
      approximately Cu(+).

PMID- 11466792
TI  - Application of the combination of isotope ratio monitoring with isotope dilution
      mass spectrometry to the determination of glucose in serum.
AB  - Isotope ratio monitoring combined with n((13)C)/n((12)C) isotope dilution mass
      spectrometry (IRM/IDMS) provides results of low uncertainty of the order of 0.1%
      if it is applied to the analysis of simple mixtures as found in organic
      chemistry, even if only low (13)C spike additives to the sample are used. If the
      method is applied to the analysis of systems that require large-scale sample
      preparation prior to the measurement, such as the determination of glucose in
      serum, the results obtained exhibit a higher uncertainty that is comparable to
      that of the conventional gas chromatography/isotope dilution mass spectrometry
      (GC/IDMS) method. The reason for this observation is that the small contribution
      that the IRM/IDMS method makes to the uncertainty budget of the result is
      superimposed on a large contribution due to the sample preparation. It appears
      therefore that the IRM/IDMS method has no advantage over the conventional GC/IDMS
      method. However, if a series of measurements is carried out, and if a suitable
      experimental design is chosen, the IRM/IDMS method can provide valuable
      additional information. The influence of sample preparation on each individual
      result can be quantified as its deviation from the average value of all results
      of the series. From these data conclusions can be drawn for an improvement in
      sample preparation.

PMID- 11466793
TI  - Application of automated matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry for the measurement of enzyme activities.
AB  - Sample preparation methods and data acquisition protocols were optimized for the
      application of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS) to high-throughput quantitative analysis of low
      molecular mass substrates and products of an enzyme-catalyzed reaction. Using a
      deuterlum-labeled internal standard, precise standard curves were obtained (r(2)
      = 0.9998) over two orders of magnitude of concentration of rac-1-phenylethylamine
      (PEA), which is converted to 2-methoxy-N-[(1R)-1-phenylethyl]acetamide (MET) by a
      lipase-catalyzed reaction with ethylmethoxyacetate (EMA) as second substrate.
      Reliable relative standard deviations were achieved (< or =5%) using automated
      analysis with peak intensity ratios between 0.2 and 5 of analyte to internal
      standard. This method permitted quantitative analysis of the lipase reaction,
      producing results comparable to those from gas chromatographic (GC) analysis in
      the dynamic range of GC. This work shows that MALDI-TOFMS can be applied for the
      high-throughput screening of enzymes.

PMID- 11466794
TI  - Characterization of inorganic coordination complexes by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - We report the direct laser desorption/ionization (LDI) and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometric (MALDI-TOFMS) analysis of
      four inorganic coordination complexes: monometallic [Ir(dpp)(2)Cl(2)](PF(6)),
      homonuclear trimetallic ([(bpy)(2)Ru(dpp)](2)RuCl(2))- (PF(6))(4), and
      heteronuclear [(tpy)Ru(tpp)Ru(tpp)RhCl(3)](PF(6))(4) and
      ([(bpy)(2)Ru(dpp)](2)IrCl(2))(PF(6))(5) (dpp = 2,3-bis-(2'-pyridyl)pyrazine, bpy
      = 2,2'-bipyridine, tpy = 2,2',6',2"-terpyradine, tpp = 2,3,5,6,-tetrakis-(2'
      pyridyl)pyrazine). Spectral intensities and fragmentation patterns are compared
      and evaluated for instrument parameters, matrix selection, and matrix-to-analyte
      ratio. Direct LDI and MALDI mass spectra of the monometallic complex showed the
      same ion peaks and differed only in the relative peak intensities. Direct LDI of
      the trimetallic complexes produced only low-mass fragments containing one metal
      at most. MALDI spectra of the trimetallic complexes exhibited little
      fragmentation in the high-mass region (>1500 Da) and less fragmentation in the
      low-mass region compared to direct LDI. Significant fragments of the molecules
      were detected and identified, including ligand fragments, intermediate-mass
      fragments such as [Ru(tpy)](+), and molecular ions with varying degrees of PF(6)(
      ) loss ([M - n(PF(6))](+), where n = 1-3). A correlation exists between the
      solution-phase electrochemistry and the observed [M - n(PF(6))](+) series of
      peaks for the trimetallic complexes. Proper matrix selection for MALDI analysis
      was vital, as was an appropriate matrix-to-analyte ratio. The results demonstrate
      the applicability of MALDI-TOFMS for the structural characterization of labile
      inorganic coordination complexes.

PMID- 11466795
TI  - Formation of gas-phase clusters monitored during electrospray mass spectrometry:
      a study of quaternary ammonium pesticides.
AB  - Gas-phase cluster formation between the quaternary ammonium pesticides paraquat,
      diquat, difenzoquat, chlormequat and mepiquat, and chloride and acetate anions
      present in a liquid chromatography (LC) mobile phase, has been studied using
      electrospray mass spectrometry. The clusters of paraquat, mepiquat and
      chlormequat were revealed over the entire m/z range of the mass spectrometer, and
      their formation is dependent on the concentrations of both the cationic and the
      anionic species. Mepiquat and chlormequat form clusters of the type [2M(q)(+) +
      A(-)](+), where M(q)(+) is the quaternary ammonium cation and A(-) is the anion.
      Paraquat forms a cluster species with ammonia and also an ion-pair complex with
      chloride anions. Diquat and difenzoquat did not form observable ion-pair
      complexes or clusters with any of the anions studied. Competitive binding of
      acetate and chloride anions reflects the higher charge density of chloride, which
      forms the dominant clusters with mepiquat and chlormequat. The formation of
      cluster species has implications for the quantification of quaternary ammonium
      pesticides and may have an influence on the linearity of calibrations.

PMID- 11466796
TI  - Theoretical evaluation of error in the isotopic analysis of carbon and oxygen as
      CO (2)(+): considerations for determining two different isotopic abundance ratios
      simultaneously.
AB  - The computations involved in the CO(2)(+) ion beam method of determining
      simultaneously a pair of constituent elemental isotopic abundance ratios P and Q
      (viz. (13)C/(12)C and (17)O/(16)O, or (13)C/(12)C and (18)O/(16)O, or (17)O/(16)O
      and (18)O/(16)O) are worked out, and the possible implications of their
      involvement as an analytical step are evaluated theoretically. It is shown, as an
      immediate consequence, that accurate measurements of the required isotopic
      CO(2)(+) abundance ratios (R(j) and R(k)) do not necessarily mean that the
      results (P; Q) are equally accurate. It is demonstrated that, and also explained
      why, the results can be far more inaccurate, or even in some cases more accurate,
      than the (R(j);R(k)) values themselves. It is clarified how the errors of
      analysis (delta(P) and delta(Q)) are actually governed, and elaborated further by
      evaluating their variations as a function of different possible parameters which
      control their magnitudes. The investigations thus help to predict the required
      analytical conditions for accurate isotopic analysis of carbon and/or oxygen
      samples of any origin as CO(2)(+). The considerations for the case of natural
      samples predict that, while it should be generally possible to simultaneously
      determine the isotopic abundance ratios of (13)C/(12)C and (18)O/(16)O with an
      accuracy better than the measurements themselves, the determination of either the
      ((13)C/(12)C and (17)O/(16)O) ratios or the ((17)O/(16)O and (18)O/(16)O) ratios,
      with an accuracy as good as that of the measurements, would be extremely
      difficult and may, in practice, be impossible.

PMID- 11466797
TI  - New aspects in matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry: a universal solvent-free sample preparation.
AB  - A method of solvent-free sample preparation is shown to be of universal
      applicability for matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS). Results obtained were compared with those of traditional solvent
      based sample preparation for MALDI-MS in order to demonstrate their similarities
      with respect to accuracy, sensitivity and resolution for polymers such as
      polystyrene and poly(methyl methacrylate) in a mass range from 2 to 100 kDa. The
      results revealed that there is fundamentally no difference in the quality of the
      obtained mass spectra, and we conclude that the mechanism of desorption and
      ionization remains unchanged. However, the solvent-free sample preparation turned
      out to have some advantages over the traditional method in certain cases: quick
      and easy applicability is shown for polyetherimide avoiding time-consuming
      optimization procedures. In particular, industrial pigments that are insoluble in
      common solvents were characterized without interfering signals from fragments.
      The method even showed improvements with respect to reproducibility and mass
      discrimination effects in comparison to traditional sample preparation.
      Additionally, this contribution provides new insight regarding the analyte/matrix
      preorganization for the desorption step which now appears to be independent of
      crystallinity.

PMID- 11466798
TI  - Mass spectrometric studies on pyridine-piperazine-containing ligands and their
      complexes with transition metals formed in solution.
AB  - Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization
      (MALDI) methods were used to study open-chain piperazine-containing ligands (L)
      and their complexes formed with transition-metal salts. ESI and MALDI
      measurements were performed with a Fourier transform ion cyclotron resonance (FT
      ICR) and a time-of-flight (TOF) mass spectrometer, respectively. Only singly
      charged complexes, between one ligand and one or several metal ions, were formed
      in the ESI measurements. Because the net charge was always one, one or several
      counterions were attached to the complex. Under ESI conditions, the complexes
      formed between the ligands and metal (Co, Ni, Cu, and Cd) salts were [L + M +
      X](+), [L + H + M + X(2)](+) and [L + M(2) + X(3)](+) (M = metal ion, X =
      counterion). In collision induced dissociation reactions the [L + H + M +
      X(2)](+) complexes easily eliminated one proton and one counterion. Fragmentation
      pathways were more dependent on the metal ion than the ligand, and elimination of
      the second counterion occurred with one proton from copper and nickel complexes
      and with one proton and one hydrogen from cobalt complexes. Differences in the
      fragmentation of the complexes could be due to electronic configuration of the
      metal ion. In the MALDI measurements the ratio between the [L + H](+) and [L -
      H](+) ions varied with the matrix. Fragmentation of the ligands through
      elimination of 2-methylpyridine end groups occurred with the aromatic matrices
      containing carboxylic acid and hydroxyl substituents. Ionization of the complexes
      was not successful with MALDI as the matrix molecules were also attached to the
      complexes.

PMID- 11466800
TI  - A discrete random effects probit model with application to the demand for
      preventive care.
AB  - I have developed a random effects probit model in which the distribution of the
      random intercept is approximated by a discrete density. Monte Carlo results show
      that only three to four points of support are required for the discrete density
      to closely mimic normal and chi-squared densities and provide unbiased estimates
      of the structural parameters and the variance of the random intercept. The
      empirical application shows that both observed family characteristics and
      unobserved family-level heterogeneity are important determinants of the demand
      for preventive care.

PMID- 11466801
TI  - The performance of sample selection estimators to control for attrition bias.
AB  - Sample attrition is a potential source of selection bias in experimental, as well
      as non-experimental programme evaluation. For labour market outcomes, such as
      employment status and earnings, missing data problems caused by attrition can be
      circumvented by the collection of follow-up data from administrative registers.
      For most non-labour market outcomes, however, investigators must rely on
      participants' willingness to co-operate in keeping detailed follow-up records and
      statistical correction procedures to identify and adjust for attrition bias. This
      paper combines survey and register data from a Norwegian randomized field trial
      to evaluate the performance of parametric and semi-parametric sample selection
      estimators commonly used to correct for attrition bias. The considered estimators
      work well in terms of producing point estimates of treatment effects close to the
      experimental benchmark estimates. Results are sensitive to exclusion
      restrictions. The analysis also demonstrates an inherent paradox in the 'common
      support' approach, which prescribes exclusion from the analysis of observations
      outside of common support for the selection probability. The more important
      treatment status is as a determinant of attrition, the larger is the proportion
      of treated with support for the selection probability outside the range, for
      which comparison with untreated counterparts is possible.

PMID- 11466802
TI  - Estimating treatment effects in randomized clinical trials with non-compliance:
      the impact of maternal smoking on birthweight.
AB  - This paper assesses the causal impact of late-term (8th month) maternal smoking
      on birthweight using data from a randomized clinical trial, in which some women
      were encouraged not to smoke, while others were not. The estimation of treatment
      effects in this case is made difficult as a result of the presence of non
      compliers, women who would not change their smoking status, regardless of the
      receipt of encouragement. Because these women are not at risk of changing
      treatment status, treatment effect distributions may be difficult to construct
      for them. Consequently, the paper focuses on obtaining the distribution of
      treatment impacts for the sub-set of compliers found in the data. Because
      compliance status is not observed for all subjects in the sample, a Bayesian
      finite mixture model is estimated that recovers the treatment effect parameters
      of interest. The complier average treatment effect implies that smokers give
      birth to infants weighing 348 g less than those of non-smokers, on average,
      although the 95% posterior density interval contains zero. The treatment effect
      is stronger for women who were moderate smokers prior to pregnancy, implying a
      birthweight difference of 430 g. However, the model predicts that only about 22%
      of the women in the sample were at risk of changing their smoking behaviour in
      response to encouragement to quit.

PMID- 11466803
TI  - Proportional treatment effects for count response panel data: effects of binary
      exercise on health care demand.
AB  - We define conditional and marginal treatment effects appropriate for count data,
      and then conduct an empirical analysis for the effects of exercise on health care
      demand using panel data from the Health Retirement Study. The response variables
      are office visits to doctors and hospitalization days, and the treatments of
      interest are light and vigorous exercises. We found that short-run light exercise
      increases health care demand by 3-5%, whereas long-run light exercise decreases
      it by 3-6%. We also found that short-run vigorous exercise decreases health care
      demand by 1-2%, whereas long-run vigorous exercise decreases it by 1-3%. However,
      many of these numbers are not statistically significantly different from zero.
      These findings suggest that it will be difficult to reduce health care cost much
      by encouraging people to do more exercise--at least in the short-run.

PMID- 11466804
TI  - Live long, live well: quantifying the health of heterogeneous populations.
AB  - Various health, quality, utility and disability adjusted life years or life
      expectancy (HALY, QALY, DALY; HALE, QALE, DALE) measures have become gold
      standards for defining outcomes in technology evaluation, population health
      monitoring, and other evaluative efforts. As such, the analytical framework
      within which these measures are used for descriptive and evaluative purposes
      should be theoretically consistent and statistically rigorous. For instance,
      widely accepted definitions of cost-effectiveness ratios and other technology
      evaluation criteria that are based on expectations of the respective cost and
      outcome measures must, as such, be defined in terms of expected HALYs or QALYs.
      Similarly, measures like HALEs or QALEs used for population health monitoring are
      typically concerned with population expectations of such measures (or their
      corresponding totals). This paper demonstrates that estimation of such
      expectations necessitates consideration of the population variation in, and
      covariation between, quality and longevity. From the perspective of several
      different environments characterizing such heterogeneity, quantification or
      estimation of measures like QALYs is reconsidered. An empirical example of the
      central issues is provided by means of an analysis of the years of healthy life
      (YHL) measure drawn from the US National Health Interview Survey.

PMID- 11466805
TI  - The effect of variable health insurance deductibles on the demand for physician
      visits.
AB  - In order to contain cost in the health care sector, the introduction of consumer
      incentives in health insurance has been suggested and realized in many countries.
      The Swiss health system reform of 1996 introduced a choice of deductible for
      health services in the mandatory basic health insurance. This paper estimates the
      effect of this choice on physician service utilization. A generalized method of
      moments (GMM) estimator is applied to take account of the endogeneity of the
      choice of the deductible in the estimation of the number of physician visits.
      This paper finds that most of the observed reduction in the number of physician
      visits among individuals who choose a higher deductible seems to be a result of
      self-selection of individuals into the respective insurance contracts, and not to
      induced changes in utilization behaviour.

PMID- 11466806
TI  - Effects of cost sharing on physician utilization under favourable conditions for
      supplier-induced demand.
AB  - The effects of cost sharing on the demand for ambulatory care in experimental
      circumstances are well understood since the Rand Health Insurance Experiment
      (HIE). However, in a non-experimental real-world context, supplier-induced demand
      of doctors might erode some of the significant negative out-of-pocket price
      elasticity identified in the HIE. Belgium is an interesting test case for this
      hypothesis because it has relatively high rates of patient cost sharing in its
      public health insurance system and a very high density of physicians, all
      remunerated fee-for-service. We have exploited the price variation generated by a
      substantial increase in patient co-payment rates in 1994 to estimate out-of
      pocket price elasticities for three groups of users, and for three types of
      services using a fixed-effects model in levels and in differences. We obtain
      significant out-of-pocket price elasticities for the general population in the
      range from -0.39 to -0.28 for GP home visits, -0.16 to -0.12 for GP office visits
      and -0.10 for specialist visits. The estimates were generally lower and less
      significant for the groups of elderly and disabled. The differences we find in
      price responsiveness appear to be fairly robust and consistent with the HIE
      predictions. These results suggest that--at least in the short run--non
      experimental utilization effects of cost sharing are very similar to the
      experimental evidence, even in a situation of favourable conditions for supplier
      induced demand.

PMID- 11466807
TI  - Stochastic league tables: communicating cost-effectiveness results to decision
      makers.
AB  - The presentation of the results of uncertainty analysis in cost-effectiveness
      analysis (CEA) in the literature has been relatively academic with little
      attention paid to the question of how decision-makers should interpret the
      information particularly when confidence intervals overlap. This question is
      especially relevant to sectorial CEA providing information on the costs and
      effects of a wide range of interventions. This paper introduces stochastic league
      tables to inform decision-makers about the probability that a specific
      intervention would be included in the optimal mix of interventions for various
      levels of resource availability, taking into account the uncertainty surrounding
      costs and effectiveness. This information helps decision-makers decide on the
      relative attractiveness of different intervention mixes, and also on the
      implications for trading gains in efficiency for gains in other goals such as
      reducing health inequalities and increasing health system responsiveness.

PMID- 11466808
TI  - Cytotechnologists. Do we have enough?

PMID- 11466809
TI  - Cervical cytology practice guideline. American Society of Cytopathology.

PMID- 11466810
TI  - Cytodiagnosis of nipple discharge: a study of 602 samples from 484 cases.
AB  - To find out the gross and microscopic differentiating features between nipple
      discharges (ND) due to various breast lesions, smears of 602 ND samples from 484
      cases were reviewed by one of the investigators (D.K.D.). The reviewed
      cytodiagnoses were as follows: benign nipple discharge (59.1%), inflammatory ND
      (6.5%), ?papillary lesions (2.5%), papillary lesions (20.6%), papillary lesions
      with atypia (3.8%), duct cells with atypia (0.2%), suspicious for malignancy
      (0.5%), malignant ND (1.2%), and inadequate (5.6%). Following review, samples
      with epithelial abnormalities (?papillary lesion, papillary lesion with and
      without atypia, duct cells with atypia, suspicious for malignancy, and
      malignancy) increased from 16.6% to 30.4% of adequate samples (P < 0.0001). 37.9%
      unilateral ND samples showed epithelial abnormalities, as opposed to 18.9% of
      bilateral ND samples (P < 0.0001). Bloodstained ND showed epithelial
      abnormalities in 41.5% samples, as compared to 22.1% of ND with other specified
      gross characteristics (P < 0.0001). The samples with epithelial abnormalities
      differed significantly from benign and inflammatory ND in respect of frequency of
      benign duct cells, duct cells with atypia, papillary clusters with or without
      atypia, malignant cells, columnar cells, red blood cells, inflammatory cells, and
      background lipid vacuoles (P < 0.01 to < 0.0001). The ND samples with suspicious
      and malignant cytology, besides the presence of malignant cells (P < 0.0001),
      differed significantly from rest of the lesions in respect of foam cells (P <
      0.0001), red blood cells (P < 0.01), and inflammatory cells (P < 0.05). When
      compared with histopathological diagnosis in 20 cases, the benign or malignant
      nature of the lesion was correctly identified in ND in 80% cases. The ND
      cytologies in 7 histologically proved malignant cases were malignancy (3 cases),
      suspicious for malignancy (1 case), papillary lesion with atypia (1 case),
      papillary lesion (1 case), and benign ND (1 case).

PMID- 11466811
TI  - Atypical squamous epithelium in cytologic specimens from the pancreas:
      cytological differential diagnosis and clinical implications.
AB  - Atypical squamous epithelium is an uncommon finding in cytologic specimens
      obtained from pancreatic lesions. A variety of pathologic conditions can result
      in the presence of these cells, including primary or metastatic carcinomas,
      chronic pancreatitis, and squamous metaplasia related to pancreatic or biliary
      duct stent placement. Primary adenosquamous and squamous-cell carcinomas of the
      pancreas are rare, representing 3.4% and 1.4 % of pancreatic carcinomas,
      respectively. Cytologic separation of these malignancies from less ominous
      metaplasias has immense clinical importance. We reviewed Indiana University
      Hospital's and Duke University's experiences with atypical squamous epithelium
      occurring within pancreatic aspirates. Study cases were identified using a
      computer to search the cytology records of these two institutions. Nine cases
      with a diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or atypical
      squamous epithelium were retrieved from the two institutions' Department of
      Pathology files. One case of pure squamous-cell carcinoma occurred in a patient
      with a known pulmonary primary; a single case of adenosquamous carcinoma was
      diagnosed in a patient with a coexistent endometrial primary; a single sample of
      adenocarcinoma with squamous differentiation was diagnosed in a patient without
      other known disease; and four primary squamous-cell carcinomas of the pancreas
      were detected. In addition, a single case of atypical squamous metaplasia
      associated with a stent was identified, and one case of atypical squamous
      epithelium associated with chronic pancreatitis was diagnosed. Despite the
      reactive atypia present in the examples of metaplastic squamous epithelium,
      separation of these cases from true squamous-cell carcinoma and adenosquamous
      carcinoma was achievable by cytologic evaluation. No cytologic criteria aided in
      separating primary pancreatic carcinomas with squamous differentiation from
      metastatic lesions. In this study, we report our findings in a series of nine
      cases where cytology disclosed atypical squamous epithelium in the aspirates
      derived from pancreatic lesions.

PMID- 11466812
TI  - Radiologically guided percutaneous fine-needle aspiration biopsy of pelvic and
      retroperitoneal masses: a retrospective study of 68 cases.
AB  - Fine-needle aspiration (FNA) of the pelvis and retroperitoneum (excluding the
      pancreas, kidney, and adrenal masses) has not achieved its full potential as a
      diagnostic modality. We reviewed 68 percutaneous, radiologically guided FNAs from
      these locations to assess the clinical utility and complication rate of this
      procedure. Satisfactory material was obtained in 66 cases (97.1%), of which 37
      were deemed positive (55%), 3 suspicious (4%), 4 atypical (6%), and 22 negative
      (32%) for malignancy; two cases (3%) were unsatisfactory. Compared to biopsy (36
      patients) and clinical information, the sensitivity and specificity of FNA for
      malignancy were 90.2% and 100%, respectively, yielding a positive predictive
      value of 100% and a negative predictive value of 86.6%. The four false-negative
      cases (5.9%) were due to sampling error. One patient had a minor complication
      (hematoma) from the procedure. We conclude that FNA is the procedure of choice
      for detecting most malignancies in these two locations.

PMID- 11466813
TI  - Primary pleural effusion posttransplant lymphoproliferative disorder: Distinction
      from secondary involvement and effusion lymphoma.
AB  - Pleural effusion presentation of posttransplant lymphoproliferative disorder
      (PTLD) is relatively uncommon. Most examples of effusion-based PTLD have been
      secondary to widespread solid organ involvement, and are associated with an
      aggressive clinical course. We report on a case of primary effusion PTLD in a 70
      yr-old male liver transplant recipient with a history of hepatitis B infection.
      Cytomorphologically, the pleural fluid specimen showed a monomorphous population
      of intermediate to large-sized transformed lymphoid cells, with irregular
      multilobated nuclear contours and readily identifiable mitotic figures. Flow
      cytometric immunophenotypic studies revealed a CD5-negative, CD10-negative,
      lambda immunoglobulin light chain-positive, monoclonal B-lymphocyte (CD19
      positive/CD20-positive) population. The immunocytochemical stain for CD30 antigen
      was negative. In situ hybridization study for Epstein-Barr virus (EBV) early RNA
      (EBER) and Southern blot analysis for EBV terminal repeat sequences were both
      positive. Southern blot analysis for human herpes virus-8 (HHV-8) was negative.
      No solid-organ PTLD was identified, and the cytologic results supported the
      diagnosis of primary effusion PTLD. Immunosuppression was decreased, and 8 mo
      following the diagnosis of pleural fluid PTLD, the patient was stable and his
      pleural effusion had markedly diminished. Recognition of primary effusion PTLD
      and its distinction from PTLD secondarily involving the body fluids and from
      other lymphomas is important, since the behavior and prognosis appear different.

PMID- 11466814
TI  - Utility of CK7 and CK20 immunohistochemistry in the detection of synchronous
      breast and colon carcinoma in a pleural effusion: a case report and supporting
      survey of archival material.
AB  - We present a case of synchronous breast and colon carcinoma in a pleural
      effusion, to our knowledge the first such reported case in the English-language
      literature. The patient was a 55-yr-old white female with known metastatic breast
      and colon carcinoma who developed a malignant pleural effusion which demonstrated
      two strikingly different populations of malignant cells by immunohistochemical
      study of cell block material. One cell population demonstrated a cytokeratin
      (CK)7+/CK20-/ER+ phenotype, while the other demonstrated a CK7-/CK20+/ER-
      phenotype, consistent with breast and colon origin, respectively. An
      immunohistochemical survey of archival breast and colon primary and metastatic
      carcinomas confirmed the established CK7+/CK20- phenotype of breast and CK7
      /CK20+ phenotype of colon primary carcinomas, and the maintenance of this
      phenotype in metastases thereof. A survey of benign and malignant mesothelial
      lesions confirmed the absence of staining for estrogen receptor, but showed 6/10
      cases weakly positive for CK20, which has not been described in other published
      series. This unusual case graphically illustrates the utility of cytokeratin
      subset immunohistochemistry in effusion cytology.

PMID- 11466815
TI  - Amylase crystalloids in salivary gland lesions: report of a case with a review of
      the literature.
AB  - Several types of crystalloids may be found in fine-needle aspiration cytology of
      salivary gland lesions. Amylase crystalloids (sometimes referred to as
      nontyrosine crystalloids) are tabular structures with frequent pointed ends that
      have received little attention until recent years. We report on a parotid cyst
      containing the latter type of crystalloids in a 51-yr-old white woman. The
      cytologic and radiologic findings were diagnostic of sialolithiasis. To the best
      of our knowledge, amylase crystalloids have been observed only in benign salivary
      gland lesions. Although this statement may be helpful in the diagnostic workup of
      patients presenting with parotid lumps, we do not recommend rendering a specific
      diagnosis based on the presence of such crystalloids. Good clinical and
      radiological correlation, as well as close follow-up, is mandatory in this
      setting.

PMID- 11466816
TI  - Aspiration biopsy of osseous metastasis of occult hepatocellular carcinoma: Case
      report, literature review, and differential diagnosis.
AB  - Fine-needle aspiration (FNA) cytology is a reliable technique for rapid diagnosis
      in virtually every organ of the body, including bone lesions. We report on the
      FNA findings in a 61-yr-old male of an osteolytic sacral lesion, which determined
      the diagnosis of an unsuspected metastatic hepatocellular carcinoma. In this
      case, the diagnosis was confirmed by FNA biopsy without resorting to surgical
      biopsy.

PMID- 11466817
TI  - Desmoplastic small round cell tumor presenting as a neck mass: a case report.
AB  - An unusual case study of a desmoplastic small round cell tumor presenting as a
      3.5-cm, firm, supraclavicular neck mass and diagnosed by fine-needle aspirate
      biopsy in a 16-yr-old male is reported. Clinical, cytologic, and
      immunocytochemical findings are described. Histologic, immunohistochemical, and
      genetic features are discussed. Desmoplastic small round cell tumor should be
      considered in the differential diagnosis of small round cell tumors of any site;
      the importance of ancillary studies in arriving at the correct diagnosis is
      emphasized.

PMID- 11466818
TI  - Fine-needle aspiration cytology of the breast: Invasive vs. in situ carcinoma.
AB  - The surgical management of invasive breast carcinoma differs from that of in situ
      disease. Invasive carcinoma necessitates axillary lymph node dissection, a
      procedure that has associated morbidity. We studied 80 cases (66 invasive, 14 in
      situ) of breast carcinoma that had a histological diagnosis and a preoperative
      fine-needle aspirate. All slides were reviewed, with 17 cytologic features
      assessed. We found that six of these features showed a statistically significant
      difference between the invasive and in situ cases. These were infiltration of fat
      or stroma by malignant cells (72% of invasive cases demonstrated this feature,
      but it was not present in any of the in situ cases, P = 0.0002), the presence of
      myoepithelial cells overlying clusters of tumor cells (seen in 86% of in situ
      tumors and 7% of invasive cases, P < 0.00001), calcification (present in 71% of
      in situ and 15% of the invasive group, P = 0.001), foamy macrophages (noted in
      64% of in situ tumors and 16% of invasive carcinomas, P = 0.0007),
      intracytoplasmic vacuoles (seen in 50% of invasive cases and 21% of in situ
      lesions, P = 0.08), and tubules (present in 30% of invasive and 7% of in situ
      tumors, P = 0.10). We demonstrate that invasion can be suggested in fine-needle
      aspirates of carcinomas, provided that true infiltration of fibrofatty connective
      tissue by neoplastic cells is present. In situ disease has characteristic
      features, but the presence of invasion cannot be excluded, even in the presence
      of stromal or adipose tissue fragments without tumor infiltration.

PMID- 11466819
TI  - Comparison of antibodies to MART-1 and MelanA in fine-needle aspiration samples
      of metastatic malignant melanoma.

PMID- 11466820
TI  - Fine-needle aspiration of follicular variant of papillary carcinoma in a
      hyperfunctioning thyroid nodule.

PMID- 11466821
TI  - [Chronic heart failure, an increasingly common problem].

PMID- 11466822
TI  - [The changing clinical picture and treatment of heart failure].

PMID- 11466823
TI  - [Asymptomatic left ventricular systolic dysfunction].

PMID- 11466824
TI  - [Systolic and diastolic function and dysfunction].

PMID- 11466825
TI  - [Apoptosis in heart failure, is the myocardium destroying itself?].

PMID- 11466826
TI  - [Neurohumoral changes in heart failure].

PMID- 11466827
TI  - [The factors limiting exercise capacity in heart failure, does physical training
      have effect?].

PMID- 11466828
TI  - [Diagnosing heart failure, but keeping its pitfalls in mind].

PMID- 11466829
TI  - [Identifying causes and mechanism of heart failure].

PMID- 11466830
TI  - [Special features of heart failure in the erderly].

PMID- 11466831
TI  - [Drug therapy in chronic heart failure].

PMID- 11466832
TI  - [Treatment of arrhythmias in heart failure].

PMID- 11466833
TI  - [Surgical treatment of severe heart failure].

PMID- 11466834
TI  - [Taking care of the blood circulation in intraabdominal organs, a solution for
      prevention and treatment of multiple organ failure].

PMID- 11466835
TI  - [Children, adolescents and coronary artey disease].

PMID- 11466836
TI  - [CATCH-22: a microdeletion of chromosome 22 behind the polymorphous syndrome].

PMID- 11466837
TI  - [Infant sleep apnea behind the life threatening cyanotic episodes, a good
      response to cpap treatment].

PMID- 11466838
TI  - [An elevated creatinine value, what else should be investigated?].

PMID- 11466839
TI  - [Resuscitation training in different circumstences, studying the pedgogy of
      medicine].

PMID- 11466840
TI  - [From being constipated to being ventilated].

PMID- 11466841
TI  - [Should all the births be centralized in order to reduce maternal mortality].

PMID- 11466842
TI  - [More information about a case report].

PMID- 11466843
TI  - [Are ectopic pregnancies are reducing?].

PMID- 11466844
TI  - [From contraception to treatment of sexual health].

PMID- 11466845
TI  - [When is not possible to find a suitable method of contraception].

PMID- 11466846
TI  - [Contraception in the next millenium].

PMID- 11466847
TI  - [How to choose a contraceptive pill that suits?].

PMID- 11466848
TI  - [Contraception after childbirth and abortion].

PMID- 11466849
TI  - [New possibilities of barrier contraceptives].

PMID- 11466850
TI  - [Post-coital contraception].

PMID- 11466851
TI  - [Indication for sterilization].

PMID- 11466852
TI  - [Family planning services].

PMID- 11466853
TI  - [Current treatment of chronic lymphocytic leukemia].

PMID- 11466854
TI  - [Respiratory distress syndrome of neonates today].

PMID- 11466855
TI  - [New possibilities to recognize and treat immunoneuropathies].

PMID- 11466856
TI  - [Status epilepticus in children from urine sample to gene error].

PMID- 11466857
TI  - [Hemorrhage after pyelostomy in a patient refusing blood transfusion].

PMID- 11466858
TI  - [Nephrocalcinosis caused by self treatment with antacids].

PMID- 11466859
TI  - [A high level of hemoglobin].

PMID- 11466860
TI  - [The treatment of hepatitis C].

PMID- 11466861
TI  - [A person with work mania].

PMID- 11466862
TI  - [Testosterone and libido].

PMID- 11466863
TI  - [The effects of testosterone are controversial].

PMID- 11466864
TI  - [A preliminary anthropological hypothesis of multiple sclerosis].

PMID- 11466865
TI  - [Enterococci resistant to antimicrobial agents].

PMID- 11466866
TI  - [Genetic risks increasing when a sperm is forced into an ovum].

PMID- 11466867
TI  - [A vaccination would prevent invasive pneumococcal infections in adults].

PMID- 11466868
TI  - [Dolly and ethics of cloning].

PMID- 11466869
TI  - [Adjuvant therapy of colorectal cancers].

PMID- 11466870
TI  - [The clinical significance of endothelin].

PMID- 11466871
TI  - [Sinus thrombosis].

PMID- 11466872
TI  - [Meningeal enhancement of magnetic resonance imaging in a patient with liqour
      fistula].

PMID- 11466873
TI  - [A dissociative disorder or psychosis].

PMID- 11466874
TI  - [The diagnostics of syphilis today].

PMID- 11466875
TI  - [A patient with persistent arrythmias and eczema].

PMID- 11466876
TI  - [Melatonin as a drug].

PMID- 11466877
TI  - [Who forgot magnesium].

PMID- 11466878
TI  - [A tip how to treat diarrhea caused by biliary acids].

PMID- 11466879
TI  - [At last some facts about alcoholism].

PMID- 11466880
TI  - [Following Arvo Ylppo's footmarks].

PMID- 11466881
TI  - [Should the treatment of children be the first priority?].

PMID- 11466882
TI  - [What diseases affect Finnish children?].

PMID- 11466883
TI  - [Adolescents behavior].

PMID- 11466884
TI  - [Health of Finnish children and adolescents].

PMID- 11466885
TI  - [When the child has a cough].

PMID- 11466886
TI  - [Who should get antimicrobial treatment?].

PMID- 11466887
TI  - [Recurring abdominal pain in children].

PMID- 11466888
TI  - [When food does not suit you].

PMID- 11466889
TI  - [Breast-feeding and growth].

PMID- 11466890
TI  - [The importance of early detection of asthma in children].

PMID- 11466891
TI  - [Whats new concerning endocrinology of puberty].

PMID- 11466892
TI  - [From a girl to a women, from a boy to a man].

PMID- 11466893
TI  - [Good treatment of diabetes].

PMID- 11466894
TI  - [Severe kidney diseases in children].

PMID- 11466895
TI  - [Th outcome of very low birth weight infants].

PMID- 11466896
TI  - [The outcome of child with congenital heart disease].

PMID- 11466897
TI  - [Leukemia treatment results have improved, but prognosis is still questionable].

PMID- 11466898
TI  - [Intraoperative warming of the patient is profitable].

PMID- 11466899
TI  - [Pigs for spare parts].

PMID- 11466900
TI  - [Kaposi's sarcoma another new infectious disease?].

PMID- 11466901
TI  - [The fascinating world of a cell membrane from basics research to clinical
      applications].

PMID- 11466902
TI  - [Receptors for viruses].

PMID- 11466903
TI  - [Functional magnetic resonance imaging of the brain].

PMID- 11466904
TI  - [Gingival tumor associated with joint pain].

PMID- 11466905
TI  - [Jarish-Herxheimer reaction during the treatment of Lyme disease caused
      episcleritis].

PMID- 11466906
TI  - [Sore mouth, a problem of middle aged women].

PMID- 11466907
TI  - [Joint pains, neurological symptoms and hypergammaglobulinemia].

PMID- 11466908
TI  - [Treating eczema with lye].

PMID- 11466909
TI  - [A good statement from a radiologist ands its terminology].

PMID- 11466910
TI  - [Best to be cautious with genetic food].

PMID- 11466911
TI  - [Cooperation between clinicians and pathologists].

PMID- 11466912
TI  - [Prostate cancer screening].

PMID- 11466913
TI  - [Low-dose ionising radiation and cancer risk].

PMID- 11466914
TI  - [First monoclonal antibody accepted for cancer therapy].

PMID- 11466915
TI  - [Communication deviance and schizophrenia].

PMID- 11466916
TI  - [Towards healthier life style--how can I help my patient?].

PMID- 11466917
TI  - [Cost effectiveness of hip and knee arthroplasties: a two-year follow-up study].

PMID- 11466918
TI  - [Ill from eating salad].

PMID- 11466919
TI  - [Shiitake dermatitis: shiitake mushrooms must be cooked before their use].

PMID- 11466920
TI  - [Diabetic ketoacidosis in an infant].

PMID- 11466921
TI  - [The use of aminoglycosides].

PMID- 11466922
TI  - [Recommended use of INR in the laboratory monitoring of oral anticoagulant
      treatment].

PMID- 11466923
TI  - [Treatment of deep venous thrombosis].

PMID- 11466924
TI  - [Population growth is only one among the diseases].

PMID- 11466925
TI  - [The role of shame in social phobia and its treatment].

PMID- 11466926
TI  - [Evolution theory has some weaknesses].

PMID- 11466927
TI  - [Dementia and carbamazepine medication in an elderly man].

PMID- 11466928
TI  - [A health passport would make physician's daily work easier].

PMID- 11466929
TI  - [The post-war epidemic of atopy - a price of protection against infectious
      diseases and of improved standard of living? ].

PMID- 11466930
TI  - [Stem cell transplantation for rheumatoid diseases].

PMID- 11466931
TI  - [Finnish Medical Society Duodecim: New representatives starting their work].

PMID- 11466932
TI  - [HIV positive mothers and their children].

PMID- 11466933
TI  - [When the patient is not heterosexual].

PMID- 11466934
TI  - [Laryngitis caused by a laryngeal mask airway].

PMID- 11466935
TI  - [A local tuberculosis epidemic in rural Western Finland].

PMID- 11466936
TI  - [Diagnosing pulmonary embolism with the help of computed tomography].

PMID- 11466937
TI  - [Hyperthyreosis in Basedow's disease].

PMID- 11466938
TI  - [Atypical facial pain and depression].

PMID- 11466939
TI  - [Orofacial pain- differential diagnostics].

PMID- 11466940
TI  - [Facial neuralgias].

PMID- 11466941
TI  - [Drug therapy of chronic pain and its alternatives when treating orofacial pain].

PMID- 11466942
TI  - [Physical therapy and other conservative means to treat head and neck pain].

PMID- 11466943
TI  - [Stress-related gastric mucosal lesions in neonatal intensive care patients - an
      unrecognized problem].

PMID- 11466944
TI  - [Cryptorchidism--how to examine and how to treat?].

PMID- 11466945
TI  - [Cognitive therapy--a current treatment method for psychosomatic problems].

PMID- 11466946
TI  - [The biology of lymphatic vessels - new findings ].

PMID- 11466947
TI  - [Dieting increases the absorption of cholesterol in type 2 diabetes].

PMID- 11466948
TI  - [A severe liver damage caused by disulfiram treatment].

PMID- 11466949
TI  - [Liver images].

PMID- 11466950
TI  - [Prostaglandin in the treatment of impotence].

PMID- 11466951
TI  - [Should a dissertation be a monography or a summary of several publications?].

PMID- 11466952
TI  - [Abandon certain old-fashioned terms for apoplexy!].

PMID- 11466953
TI  - Multi-drug therapy for the treatment of ALS. Introduction.

PMID- 11466954
TI  - Creatine and coenzyme Q10 in the treatment of ALS.

PMID- 11466955
TI  - Oxandrolone in ALS: preliminary analysis.

PMID- 11466956
TI  - Altered calcium homeostasis in ALS as a target for therapy.

PMID- 11466957
TI  - Riluzole.

PMID- 11466958
TI  - Immunosuppression and anti-inflammatory agents in ALS.

PMID- 11466959
TI  - Mosaic chemotherapy strategies for developing ALS/MND therapeutic approaches:
      beta-2 adrenergic agonists.

PMID- 11466960
TI  - Antioxidant therapy in ALS.

PMID- 11466961
TI  - Timing and magnitude of peak height velocity and peak tissue velocities for
      early, average, and late maturing boys and girls.
AB  - Height, weight, and tissue accrual were determined in 60 male and 53 female
      adolescents measured annually over six years using standard anthropometry and
      dual-energy X-ray absorptiometry (DXA). Annual velocities were derived, and the
      ages and magnitudes of peak height and peak tissue velocities were determined
      using a cubic spline fit to individual data. Individuals were rank ordered on the
      basis of sex and age at peak height velocity (PHV) and then divided into
      quartiles: early (lowest quartile), average (middle two quartiles), and late
      (highest quartile) maturers. Sex- and maturity-related comparisons in ages and
      magnitudes of peak height and peak tissue velocities were made. Males reached
      peak velocities significantly later than females for all tissues and had
      significantly greater magnitudes at peak. The age at PHV was negatively
      correlated with the magnitude of PHV in both sexes. At a similar maturity point
      (age at PHV) there were no differences in weight or fat mass among maturity
      groups in both sexes. Late maturing males, however, accrued more bone mineral and
      lean mass and were taller at the age of PHV compared to early maturers. Thus,
      maturational status (early, average, or late maturity) as indicated by age at PHV
      is inversely related to the magnitude of PHV in both sexes. At a similar
      maturational point there are no differences between early and late maturers for
      weight and fat mass in boys and girls.

PMID- 11466962
TI  - Relationships among tempo of maturation, midparent height, and growth in height
      of adolescent boys and girls.
AB  - The influence of rate of skeletal maturation and midparent height on growth in
      height during adolescence was analyzed on longitudinal data for 184 boys and 166
      girls from the Wroclaw Growth Study. Seven biological parameters describing the
      shape of the growth curve in stature were derived from the Preece-Baines model 1
      applied to individual serial data. Rate of skeletal maturation inferred from the
      difference between chronological and skeletal ages at 12 years in girls and 14 in
      boys. Principal components analysis of the biological parameters extracted three
      factors for boys and four for girls. The factors explained 90% and 97% of the
      total variance in boys and girls, respectively. The factors reflected attained
      size and the timing and intensity of the adolescent spurt in height. Multiple
      regression showed a high relationship between skeletal maturation rate, midparent
      height, and principal component scores. Three aspects of adolescent growth: size,
      timing, and intensity show an apparent sex difference. The timing and intensity
      of the spurt are highly affected by tempo of maturation in girls, but less so
      than in boys. It might suggest in girls a less efficient compensatory effect for
      reduced length of overall growth period in early maturers that increases height
      gain. Midparent height influences the size component during the spurt, thus
      adjusting the height parameters. The dependency between attained stature (height
      at take-off, PHV, and adult stature), timing, and initial intensity of the growth
      spurt of daughters and midparent height is greater than in sons.

PMID- 11466963
TI  - Genetic variation observed at three tetrameric short tandem repeat loci HumTHO1,
      TPOX, and CSF1PO--in five ethnic population groups of northeastern India.
AB  - This paper portrays the genetic variation observed at three tetrameric short
      tandem repeat (STR) loci HumTHO1, TPOX, and CSF1PO in five ethnic population
      groups from northeastern India. The study also specifies the suitability of use
      of these markers for forensic testing. The populations studied included three
      tribal groups (Kuki, Naga and Hmar), one Mongoloid caste group (Meitei), and a
      religious caste group (Manipuri Muslims). The loci were highly polymorphic in the
      populations, and all loci met Hardy-Weinberg expectations. No evidence for
      association of alleles among the loci was detected. The probability of match for
      the three loci of the most frequent genotype in the five population groups ranged
      between 2.6 x 10(-4) and 6.6 x 10(-5). The average heterozygosity among the
      population groups was approximately 70% with the overall extent of gene
      differentiation among the five groups being high (Gst = 0.046). Genetic affinity
      among the populations reveal very close association between the Kuki, Hmar, Naga,
      and Meitei. The Manipuri Muslims, despite being found in the same region, have
      had no admixture with these populations and maintain a substantial distance with
      the other groups. The genetic polymorphism data suggest that the studied systems
      can be used for human identity testing to estimate the frequency of a multiple
      locus STR DNA profile in population groups of northeastern India.

PMID- 11466964
TI  - Young adult height of offspring born to rural-to-urban migrant parents and urban
      born parents.
AB  - This study addresses the influence of the urban or rural origin of parents on the
      attained height of 19-year-old young adult males resident in urban centers. The
      material for the study was a 10% random sample of 19-year-old Polish conscripts
      born in 1976 and examined in 1995. The conscripts represented all regions of the
      country and all social strata. Among the total sample, only those who were born
      and raised in and who currently lived in cities with a population > 100,000
      inhabitants were retained for analysis. They were grouped by educational level of
      their parents and by family size (number of children). Within limits of
      homogeneous groups, the heights of conscripts whose parents were both of rural
      origin were compared to heights of conscripts whose parents were both of urban
      origin. Within each of nine homogeneous groups, conscripts whose parents were
      both of rural origin were, on average, taller than conscripts whose parents were
      both of urban origin. Results were similar when the origin and educational level
      of either the mother or the father, in addition to family size, were considered
      separately.

PMID- 11466965
TI  - Age at spermarche and comparison of growth and performance of pre- and post
      spermarcheal Chinese boys.
AB  - The prevalence of first ejaculation emission (spermarche) in Chinese Han boys in
      1995 was considered. The subjects were 86,744 Han boys 9 through 18 years
      randomly selected from 28 provinces. Median spermarcheal ages (MSAs) were 14.4
      and 14.6 years for urban and rural boys, respectively, and 14.3, 14.6, and 14.7
      years for the boys of 1st, 2nd, and 3rd socioeconomic classes, respectively. Two
      environmental factors, ecological and socioeconomic, had strong influence upon
      MSAs. Eight indicators of somatic growth and motor ability were compared between
      pre- and post-spermarcheal boys of the same age. Post-spermarcheal boys were
      advanced in body size, shape, and physiological function during early and middle
      puberty, but most of the difference disappeared by 16 years. Pre-spermarcheal
      boys in a given age group were more linear and had more potential for increasing
      leg length into late adolescence. Within an age group, post-spermarcheal boys had
      advanced performances in several tasks requiring endurance, strength, and power
      around the age of maximum growth, 13-15 years. At older ages, the groups did not
      differ.

PMID- 11466966
TI  - Commercial porters of eastern Nepal: health status, physical work capacity, and
      energy expenditure.
AB  - The purpose of the study was to compare full-time hill porters in eastern Nepal
      with part-time casual porters engaged primarily in subsistence farming. The 50
      porters selected for this study in Kenja (elevation 1,664 m) were young adult
      males of Tibeto-Nepali origin. Following standardized interviews, anthropometry,
      and routine physical examinations, the porters were tested in a field laboratory
      for physiological parameters associated with aerobic performance. Exercise
      testing, using a step test and indirect calorimetry, included a submaximal
      assessment of economy and a maximal-effort graded exercise test. Energy
      expenditure was measured in the field during actual tumpline load carriage. No
      statistically significant differences were found between full-time and part-time
      porters with respect to age, anthropometric characteristics, health, nutritional
      status, or aerobic power. Mean VO2 peak was 2.38 +/- 0.27 L/min (47.1 +/- 5.3
      ml/kg/min). Load-carrying economy did not differ significantly between porter
      groups. The relationship between VO2 and load was linear over the range of 10-30
      kg with a slope of 9 +/- 4 ml O2/min per kg of load. During the field test of
      actual work performance, porters expended, on average, 348 +/- 68 kcal/hr in
      carrying loads on the level and 408 +/- 60 kcal/hr in carrying loads uphill. Most
      porters stopped every 2 min, on average, to rest their loads briefly on T-headed
      resting sticks (tokmas). The technique of self-paced, intermittent exercise
      together with the modest increase in energy demands for carrying increasingly
      heavier loads allows these individuals to regulate work intensity and carry
      extremely heavy loads without creating persistent medical problems.

PMID- 11466967
TI  - Blood group, red cell, and serum protein variation in the Cabecar and Huetar, two
      Chibchan Amerindian tribes of Costa Rica.
AB  - Genetic variation, using blood groups and red cell and serum proteins, was
      surveyed in the Cabecar of Chirripo and the Huetar of Quitirrisi, Costa Rica.
      Thirty-nine loci were screened in a sample of 91 Cabecars and 40 loci in 45
      Huetars. Twenty-seven loci were monomorphic in the Cabecar and 30 in the Huetar.
      The proportions of polymorphic loci (P), out of 34 studied by electrophoresis,
      were 0.235 and 0.177, respectively. Estimated gene diversities (H) of the
      polymorphic loci were 0.050 in the Cabecar and 0.053 in the Huetar. Two
      polymorphisms, reported until now in Costa Rican and Panamanian Chibchan groups
      only, occurred at very high frequencies: TF*DGUA = 0.357 in the Cabecar, the
      highest frequency ever reported, and 0.033 in the Huetar; and PEPA*F, which
      reached 0.26 in the Cabecar and 0.29 in the Huetar. Nei's genetic distances and
      trees (two methods) were used to compare them to seven other Chibchan tribes of
      Costa Rica. The results placed both the Cabecar of Chirripo and the Huetar closer
      to the Talamancan Tribes (Bribri and Cabecar). This was an unexpected result for
      the Huetar, since linguistic studies suggested a closer relationship to the
      Guatuso. GST, DST, RST, and Dm for three Cabecar subpopulations (Atlantic,
      Chirripo, and Pacific) doubled their values compared to estimates based on
      comparison of only two subpopulations: Atlantic and Pacific. Total genetic
      diversity considering just the three Cabecar subpopulations resembled that
      obtained including them plus six other Chibchan populations of Costa Rica.

PMID- 11466968
TI  - Tracking of physical fitness components in boys and girls from the second to
      sixth grades.
AB  - The purpose of this study was to examine the tracking of field-assessed fitness
      components in boys and girls from the second to sixth grades. A total of 857
      children (448 boys and 409 girls) from 11 urban schools were tested in grade 2;
      565 children (297 boys and 268 girls) were tested again in grade 6. Only subjects
      who had completed all fitness tests on the two occasions were included in the
      analysis (n = 319: 203 boys and 116 girls). Fitness tests included a 600-m run, a
      flying-start sprint, the standing long jump, and a medicine ball throw.
      Additionally, subjects performed a skill task that involved slalom dribbling of a
      basketball. Baseline scores in grade 2 were correlated (Spearman Rank Order) with
      scores attained in grade 6. Boys had significantly (P < 0.05) better scores in
      all fitness tests compared with girls in both grades. Tracking of fitness
      components over the 4-year period in both sexes varied between 0.36 and 0.66.
      Tracking was consistently lower in girls than in boys, perhaps reflecting their
      earlier maturation.

PMID- 11466969
TI  - Genetic variance in age-related changes in running performance and growth during
      adolescence: a longitudinal twin study.
AB  - The purpose of this study was to assess an effect of genotype on the patterns of
      age-related changes in running performance and physical growth during
      adolescence. The total sample was 14 pairs of male and 25 pairs of female
      monozygotic (MZ) twins and 19 pairs of male and 15 pairs of female dizygotic (DZ)
      twins. Performance on the 50-m dash and endurance run (1,500 m for boys and 1,000
      m for girls, respectively) and stature and body mass were measured at yearly
      intervals from 12 to 17 years of age. A principal component analysis was applied
      to the longitudinal data, and within-pair resemblance in the scores on the first,
      the second, and the third principal components was compared between MZ and DZ
      twins. The analysis was conducted with both sexes pooled because of the limited
      number of twin pairs. The first two principal components explained at least 87%
      of the total variance, while the third principal component (PC3) explained a
      smaller portion of the total variance (more than 5%) in the dash and the
      endurance run. However, the total variance was explained almost entirely (more
      than 96%) by the first two components in height and mass. The first principal
      component (PC1), which explained 67-84% of the total variance, was a good
      indicator of average performance/body size of individuals during the period of
      observation. The second (PC2) and the third components (PC3) could be considered
      as indicators of the "shape" of developmental/growth curves, which were not
      related to inter-individual differences in the average performance/body size.
      Intraclass correlations (ri) of the scores on PC1 were consistently higher for MZ
      than for DZ twins, and estimated genetic variance was significant in endurance
      run, stature and body mass. The situation was the same for the scores on PC2
      and/or PC3. However, such a between-genotype difference in ri and a significant
      genetic variance were not observed in the dash. It was concluded that MZ twins
      are more similar in the patterns of age-related changes in the performance of
      endurance run and physical growth during adolescence than DZ twins, suggesting a
      genetic contribution, while there was no evidence of a genetic contribution in
      the dash.

PMID- 11466970
TI  - Phosphoglucomutase genetic polymorphism of newborns.
AB  - An association of the phosphoglucomutase locus 1 (PGM1) genetic polymorphism with
      repeated spontaneous abortion (RSA), with intrauterine development in both normal
      and diabetic pregnancies, and with fertility has been reported in previous
      studies. In view of the evolutionary interest and of a possible clinical
      relevance of PGM1 selection during intrauterine life, this study considers
      healthy puerperae, consecutive newborns, and couples with RSA as well as two
      alleles (PGM1*1 and PGM1*2). The joint maternal-neonatal PGM1 distribution in a
      sample from an Italian rural population is significantly different from that
      expected assuming Hardy-Weinberg conditions for equilibrium. Deviation is
      dependent on maternal age and parity. The joint mother-newborn PGM1 genotype
      distribution is significantly associated with a positive history of previous
      spontaneous miscarriage, suggesting that the presence of the PGM1*2 allele in the
      father predisposes to spontaneous abortion. This hypothesis is also supported by
      the observation that in couples with RSA, the delivery of a live born infant
      within 5 years from the first episode of miscarriage is negatively associated
      with the presence of a PGM1*2 allele in the husband. Altogether these
      observations suggest the hypothesis of PGM1 maternal selection at the
      reproductive level involving a differential role of PGM1*1 and PGM1*2 alleles of
      paternal origin.

PMID- 11466971
TI  - Database searching with DNA and protein sequences: an introduction.
AB  - This review of sequence database searching aims to set out current practice in
      the area, in order to give practical guidelines to the experimental biologist. It
      describes the basic principles behind the programs and enumerates the range of
      databases available in the public domain. Of these, the most important are the
      equivalent DNA databases European Molecular Biology Laboratory (EMBL), GenBank
      and DNA Databank of Japan (DDBJ), and the protein databases Swiss-Prot and
      TrEMBL. The commonly used BLAST and FASTA algorithms are described in detail and
      alternative approaches mentioned briefly. Scoring matrices used to compare amino
      acid types during protein database searches are compared, with an emphasis on the
      PAM and BLOSUM series of observed substitution matrices.

PMID- 11466972
TI  - Computer prediction of sites associated with various elements of the nuclear
      matrix.
AB  - Attachment regions of the eukaryotic chromosomal DNA to the nuclear
      scaffold/matrix (S/MARs) participate in various important cellular processes.
      However, no obvious characteristics common for these nucleotide sequences have
      been revealed, except that S/MARs are non-coding sites containing putative
      regulatory elements and binding sites of DNA-topoisomerase II. Heterogeneity
      among S/MARs can be caused by a variety of biological factors. In this paper, the
      accuracy of two S/MARs prediction programs, MAR-Finder (Singh, Kramer and
      Krawetz, 1997) and ChrClass (Glazkov, Rogozin and Glazko, 1998) are compared and
      it is concluded that both programs can be recommended for analysis of eukaryotic
      genomes. However, results of their prediction should be interpreted with caution
      since estimation of prediction accuracy of both programs needs further analysis.
      Problems of S/MARs prediction are illustrated on several examples of human
      protein-coding genes, repeated elements and the beta-globin locus from different
      mammalian species. Results of our analysis suggest that the proportion of missed
      S/MARs is lower for ChrClass, whereas the proportion of wrong S/MARs is lower for
      MAR-Finder (a default set of parameters).

PMID- 11466973
TI  - The role of pattern databases in sequence analysis.
AB  - In the wake of the numerous now-fruitful genome projects, we are entering an era
      rich in biological data. The field of bioinformatics is poised to exploit this
      information in increasingly powerful ways, but the abundance and growing
      complexity both of the data and of the tools and resources required to analyse
      them are threatening to overwhelm us. Databases and their search tools are now an
      essential part of the research environment. However, the rate of sequence
      generation and the haphazard proliferation of databases have made it difficult to
      keep pace with developments. In an age of information overload, researchers want
      rapid, easy-to-use, reliable tools for functional characterisation of newly
      determined sequences. But what are those tools? How do we access them? Which
      should we use? This review focuses on a particular type of database that is
      increasingly used in the task of routine sequence analysis--the so-called pattern
      database. The paper aims to provide an overview of the current status of pattern
      databases in common use, outlining the methods behind them and giving pointers on
      their diagnostic strengths and weaknesses.

PMID- 11466974
TI  - Mouse-human comparative map resources on the Web.
AB  - Comparative maps have been a valuable resource for extrapolating biological
      information among organisms. The relationship between mouse and human maps
      provides a framework for integrating information from each species and thereby
      increasing the utility of all available data such as gene location, structure and
      function. This review describes the various public resources, both databases and
      web sites, containing genome-wide mouse-human comparative map information
      available through the World-Wide Web. We will focus on the use and applicability
      of these resources in their current form and consider future potential
      directions.

PMID- 11466975
TI  - Searching the expressed sequence tag (EST) databases: panning for genes.
AB  - The genomes of living organisms contain many elements, including genes coding for
      proteins. The portions of the genes expressed as mature mRNA, collectively known
      as the transcriptome, represent only a small part of the genome. The expressed
      sequence tag (EST) databases contain an increasingly large part of the
      transcriptome of many species. For this reason, these databases are probably the
      most abundant source of new coding sequences available today. However, the raw
      data deposited in the EST databases are to a large extent unorganised,
      unannotated, redundant and of relatively low quality. This paper reviews some of
      the characteristics of the EST data, and the methods that can be used to find
      novel protein sequences within them. It also documents a collection of databases,
      software and web sites that can be useful to biologists interested in mining the
      EST databases over the Internet, or in establishing a local environment for such
      analyses.

PMID- 11466976
TI  - Wrapping and interoperating bioinformatics resources using CORBA.
AB  - Bioinformaticians seeking to provide services to working biologists are faced
      with the twin problems of distribution and diversity of resources. Bioinformatics
      databases are distributed around the world and exist in many kinds of storage
      forms, platforms and access paradigms. To provide adequate services to
      biologists, these distributed and diverse resources have to interoperate
      seamlessly within single applications. The Common Object Request Broker
      Architecture (CORBA) offers one technical solution to these problems. The key
      component of CORBA is its use of object orientation as an intermediate form to
      translate between different representations. This paper concentrates on an
      explanation of object orientation and how it can be used to overcome the problems
      of distribution and diversity by describing the interfaces between objects.

PMID- 11466977
TI  - Mining of assembled expressed sequence tag (EST) data for protein families:
      application to the G protein-coupled receptor superfamily.
AB  - The availability of large expressed sequence tag (EST) databases has led to a
      revolution in the way new genes are identified. Mining of these databases using
      known protein sequences as queries is a powerful technique for discovering
      orthologous and paralogous genes. The scientist is often confronted, however, by
      an enormous amount of search output owing to the inherent redundancy of EST data.
      In addition, high search sensitivity often cannot be achieved using only a single
      member of a protein superfamily as a query. In this paper a technique for
      addressing both of these issues is described. Assembled EST databases are queried
      with every member of a protein superfamily, the results are integrated and false
      positives are pruned from the set. The result is a set of assemblies enriched in
      members of the protein superfamily under consideration. The technique is applied
      to the G protein-coupled receptor (GPCR) superfamily in the construction of a
      GPCR Resource. A novel full-length human GPCR identified from the GPCR Resource
      is presented, illustrating the utility of the method.

PMID- 11466978
TI  - [Neurorehabilitation--the way ahead].

PMID- 11466979
TI  - [A new regional service for rehabilitation after very serious brain injuries. I:
      Neurorehabilitation].

PMID- 11466980
TI  - [A new regional service for rehabilitation after very serious brain injuries. II:
      Neurorehabilitation research].

PMID- 11466981
TI  - [New basis for development of anticancer drugs].
AB  - Our increased knowledge of basic molecular mechanisms involved in the growth and
      spreading of cancer has provided a new basis for development of anticancer drugs.
      As an example, matrix degrading protease systems are discussed, in particular the
      urokinase plasminogen activator (uPA) system in which inhibition of binding of
      uPA to its cellular receptor is an attractive target. However, biologically based
      drugs can in general be expected to present the same problems as conventional
      drugs, including toxic side effects due to the role of their targets under normal
      conditions, and development of resistance which among other mechanisms can be due
      to a widespread functional overlap, e.g. between different matrix degrading
      protease systems. Many still unexploited promising biological targets for cancer
      therapy are known and it is likely that a systematic, goal oriented research will
      result in many new drugs. These drugs may individually not necessarily be more
      effective than the conventional drugs, but they will, due to their different
      mechanisms of action, be well suited for use in combination with these.

PMID- 11466982
TI  - [Pharmacological treatment of children and adolescents with OCD].
AB  - This review describes the pharmacological treatment of obsessive-compulsive
      disorder (OCD) in children and adolescents. Several randomised, placebo
      controlled trials have shown the efficacy of SSRI drugs in the treatment of this
      often disabling condition. Treatment with SSRI drugs for OCD in children and
      adolescents can be considered safe, according to published experiences. Side
      effects are similar to those described in adults and about 10% of children and
      adolescents treated have had to stop the treatment, owing to side effects. The
      use of medical treatment achieves a reduction in rather than a total remission of
      obsessive-compulsive symptoms. Therefore, medical treatment should always be
      combined with other strategies, of which the cognitive behavioural therapy (CBT)
      is best documented. The need for further research is stressed, especially studies
      combining different treatment strategies, and the efficacy of treatment in the
      long term.

PMID- 11466983
TI  - [What is evidence-based medicine?].
AB  - Evidence-based medicine is based on the best results from clinical and
      epidemiological research, which is combined with clinical experience and patient
      preferences. Questions of prognosis and harm are often best elucidated in large
      cohort studies. For other clinical questions the best evidence is usually found
      by systematic review of randomised trials, if possible in the form of meta
      analyses. To make a diagnosis is, for example, not an aim in itself but a way to
      arrive at a prognosis and to suggest a treatment, provided this leads to a better
      prognosis. The most relevant, albeit rarely seen, test of a diagnostic method is
      a randomised trial. Evidence-based medicine will provide the best basis for
      evaluations of which interventions should be abandoned and which are effective
      and economically feasible. The use of evidence-based clinical guidelines will
      lead to more cost-effective treatments. It should be a national strategy that
      health care should be evidence-based.

PMID- 11466984
TI  - [Infants with colic. A heterogenous group possible to cure? Treatment by
      pediatric consultation followed by a study of the effect of zone therapy on
      incurable colic].
AB  - INTRODUCTION: The aim of the study was to investigate and treat infants with
      colic by conventional medicine followed by an investigation of the effect of
      reflexological treatment. MATERIAL AND METHODS: The investigation was
      prospective, followed by a randomised, single-blind, double-controlled,
      prospective study of reflexological treatment with an interview and diary. Sixty
      three infants aged 1-3 months referred by general practitioners with crying for >
      90 minutes a day were given a paediatric examination and intervention. The cause
      of crying was discovered in 33 infants: Vitamin D (5), elimination of cow's milk
      protein (3), and anal stenosis (3); counselling on feeding, sleep, reduction of
      stimulation, and avoidance of passive smoking (22). Thirty infants without the
      benefit of paediatric consultation were randomised to three groups for a duration
      of two weeks: A: Presumed non-effective reflexological treatment vs B: Presumed
      effective reflexological treatment vs C: No treatment--only observation. The most
      important parameter was the number of crying hours over 24 hours. Cure was
      defined as crying for less than or equal to 30 minutes. RESULTS: Examination by
      the paediatrician: Thirty-three of 63 infants benefited with a reduction in
      crying of less than 90 minutes and 13 of these infants were cured. The randomised
      study: In group C (control), none of the patients was cured. In groups A and B
      (presumed non-effective reflexological treatment and presumed effective
      treatment), half the patients were cured, which was significantly better than in
      group C. There was no significant difference between groups A and B, but B seemed
      better than group A. B was significantly better than C. DISCUSSION: Infantile
      colic had a significant cure rate at paediatric consultation and the children who
      did not benefit from this intervention had a significantly better outcome after
      reflexological treatment than had the observation group. Further investigations
      in reflexological treatment in infants are recommended.

PMID- 11466985
TI  - [Incidence of malignant mesothelioma in Denmark and expected number of future
      cases among men].
AB  - INTRODUCTION: The aim was to analyse incidence rates and to predict the future
      number of cases of malignant mesothelioma in Denmark. METHODS: We analysed the
      1912 cases of malignant mesothelioma reported to the Danish Cancer Register, 1943
      1993, in order to describe the current incidence rates. The relative risks of
      synthetic birth cohorts were estimated by a Poisson regression model and used to
      predict the future number of cases in males. RESULTS: The incidence rate
      increased to 1.33 per 100,000 person years in men in 1983-1987, and to 0.51 in
      women in 1973-1977. According to a Poisson regression model, the risk in birth
      cohorts in males peaked in the 1940-1944 cohort and decreased to 0.57 in the 1950
      1954 cohort. The age-specific incidence rate peaked at 246 per 100,000 person
      years in the age group of 80-84. The future annual number of mesothelioma cases
      is expected to peak around 2015 with 93 cases in men born before 1955.
      DISCUSSION: The fit of the model was not ideal, but with careful interpretation
      of the results we conclude that a further increase in the number of mesothelioma
      cases can be expected, and the effect of regulating the environmental exposure to
      asbestos cannot be expected within the next 10-15 years.

PMID- 11466986
TI  - [A randomized controlled trial of the use of CRP rapid test as a guide to
      treatment of respiratory infections in general practice].
AB  - INTRODUCTION: The aim was to assess whether the frequency of antibiotic
      prescriptions to patients with respiratory infections is reduced when general
      practitioners (GPs) use a CRP rapid test to support their clinical assessment,
      and to examine whether the use of the test would have any effect on the course of
      disease. MATERIAL AND METHOD: A randomised controlled trial was carried out by 35
      general practices in the County of Funen, Denmark, with 812 patients with
      respiratory infection. The main outcome measures were frequency of antibiotic
      prescriptions and morbidity one week after the consultation, as stated by the
      patients. RESULTS: The frequency of antibiotic prescriptions was 43% (179/414) in
      the CRP group and 46% (184/398) in the control group (NS, OR = 0.9). At one week,
      increased or unchanged morbidity was stated more frequently in the CRP group
      (12%) than in the control group (8%) (OR = 1.6, p = 0.05). In the control group,
      the variable having the greatest influence on whether the GP prescribed
      antibiotics was the patient's general well-being (OR = 2.9, p < 0.0001), whereas
      in the CRP group the CRP value had the greatest influence (OR = 1.1 per unit
      increase [mg/l], p < 0.0001). CONCLUSION: From on the present study, the use of a
      single CRP rapid test to support possible antibiotic treatment of respiratory
      infections in general practice cannot be recommended.

PMID- 11466987
TI  - [Reduced metabolism in cerebral cortex correlates with MRI changes and cognitive
      dysfunction in patients with disseminated sclerosis].
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) lesion load is widely used in the
      clinical evaluation of patients with multiple sclerosis (MS), but little is known
      about the associated changes in cortical activation. For this purpose, we studied
      the association between the corticocerebral metabolic rate of glucose (CMRglc)
      and the MRI T2-weighted total lesion area (TLA). In addition, we investigated the
      correlation between cognitive and neurological disability and CMRglc. METHODS:
      Twenty-three patients with clinically definite MS underwent measurements of the
      CMRglc, TLA, motor-evoked potentials (MEP), and cognitive and neurological
      disability. CMRglc was calculated with positron emission tomography (PET) and 18
      F-deoxyglucose (FDG) and compared to that of nine healthy controls. RESULTS: A
      reduction in CMRglc (p < 0.01) was found in cortical global and regional lobar
      measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the
      dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus,
      and hippocampus. Global cortical CMRglc correlated with TLA (rho = -0.66; p =
      0.001), and rCMRglc correlated with the regional lesion load in all cerebral
      lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability were also
      correlated (rho = 0.58; p = 0.015), and stepwise regression analysis showed a
      significant association between rCMRglc of the right thalamus and cognitive
      performance, as well as the TLA. There was no correlation between CMRglc and
      neurological disability (expanded disability status scale [EDSS]) or MEP.
      CONCLUSION: Global and regional cortical CMRglc is significantly reduced in
      patients with MS compared to healthy controls. The reductions in CMRglc
      furthermore correlate with the TLA, as well as with cognitive dysfunction, which
      indicates that MRI white matter lesion burden has a deteriorating effect on
      corticocerebral neural function.

PMID- 11466988
TI  - [Recurrence and survival after conventional low anterior resection for rectal
      cancer].
AB  - INTRODUCTION: The aim of the study was to evaluate the incidence of recurrence of
      local cancer, distant metastases and survival after conventional low anterior
      resection for cure in patients with rectal carcinoma, on the basis of the poor
      prognosis after colorectal cancer in Denmark. MATERIAL AND METHODS: Consecutive
      patients operated on in the nine Danish departments of surgical gastroenterology
      in 1992-1993. Retrospective collection of data on recurrence of local cancer,
      distant metastases, and over-all survival at the end of 1996. RESULTS: Of 268
      patients, 77 (29%) developed recurrent local cancer and/or distant metastases.
      Forty-eight (18%) had local recurrence with a cumulative 5-year rate of 39%.
      Distant metastases were seen in 54 (20%). The local recurrence rate increased
      with increasing Dukes' tumour stage and was higher after operation by a non
      specialist (30%) than by a consultant, another specialist, or a surgeon under
      training and supervised by a consultant (15-17%) (p = 0.04). Multiple regression
      showed that the recurrence rate was independent of tumour localisation, blood
      loss, transfusion, anastomotic leakage, and status of the surgeon. The cumulative
      crude 5-year survival was 50% and independent of the status of the surgeon.
      DISCUSSION: Our relatively high local recurrence rate and the results in the
      literature after total mesorectal excision (TME) indicate that the conventional
      technique should be replaced by TME, which has become the recommended method in
      recent years. Furthermore, we propose a changed strategy in the treatment of
      rectal cancer. The patients should be treated in fewer departments with
      established teams of rectal cancer specialists taking part in all operations for
      rectal cancer.

PMID- 11466989
TI  - [A controlled trial of training in knee arthritis].
AB  - INTRODUCTION: The aim was to investigate the effectiveness and safety of a
      physical training programme in patients with severe osteoarthritis of the knees.
      MATERIAL AND METHODS: Twenty-five patients participated in this randomised
      clinical trial with a blind observer. Intervention consisted in training twice a
      week for three months and focused on general fitness, balance, co-ordination, and
      muscle strength. Follow-up was performed at 3 and 12 months. The recorded
      parameters were muscle strength, algofunctional index, pain, walking speed, and
      clinical findings. RESULTS: At three months follow-up, muscle strength had
      improved in the intervention group. By one year, pain at night had decreased, but
      the number of palpable knee joint effusions had increased. CONCLUSION: A general
      physical training programme appears to be beneficial to patients with
      osteoarthritis of the knees, but further investigation of the safety of such a
      programme is called for.

PMID- 11466990
TI  - [Ambulatory mediastinoscopy].
AB  - INTRODUCTION: The present study was undertaken to investigate the safety of
      mediastinoscopy as a routine outpatient procedure. METHODS: We reviewed the first
      108 mediastinoscopies performed at our outpatient surgery centre. RESULTS: During
      the period, 1996 to 1999, 108 out of 206 (52%) mediastinoscopy patients were
      admitted to the outpatient surgery centre, and 86 (80%) of these were discharged
      the same day. These numbers were 86% and 86% for 1999 alone, which reflects
      acceptance of outpatient surgery. One patient was admitted because of
      preoperative mediastinal venous bleeding, which required compression for 24
      hours, and 19 more patients were admitted without strict medical indications. Two
      patients were admitted later the same day after discharge, because of minor wound
      bleeding, which was stopped by infiltration with adrenalin. DISCUSSION:
      Mediastinoscopy can be performed safely as an outpatient procedure on most
      patients.

PMID- 11466991
TI  - [Picture of the month: empty pupil, hidden lens].

PMID- 11466992
TI  - [Textiles and sunscreening creams for UV protection].

PMID- 11466993
TI  - [Determination of free and bound leptin in serum: important during thyroid
      disease?].

PMID- 11466994
TI  - [New knowledge of the cause of diabetes?].

PMID- 11466995
TI  - [Intracranial meningioma].

PMID- 11466996
TI  - [Intracranial meningioma--new knowledge!].

PMID- 11466998
TI  - [Debts to predecessors].

PMID- 11466997
TI  - [Not god enough, Ugeskriftet--and not satisfactory in these quality-conscious
      times].

PMID- 11466999
TI  - [Survival in untreated breast cancer].

PMID- 11467000
TI  - [Untreated breast cancer in Denmark].

PMID- 11467001
TI  - [Radioiodine treatment of non-toxic goiter].

PMID- 11467002
TI  - [Fish liver oil].

PMID- 11467003
TI  - [Treatment of carbon monoxide poisoning].

PMID- 11467004
TI  - ["Alternative" treatment].

PMID- 11467005
TI  - [Normal weight contra ideal weight].

PMID- 11467006
TI  - [Tennis elbow--the observed depends on the observer by whom the observation was
      done].

PMID- 11467007
TI  - [Tennis elbow].

PMID- 11467008
TI  - Hepatitis C, diagnosis and management: a survey of practicing physicians in
      Hawaii.
AB  - We surveyed 652 Hawaii physicians who diagnosed hepatitis C (HCV) since 1997.
      Less than 20% of licensed physicians have diagnosed HCV and initial estimates
      suggest there are 12,000 to 18,000 undiagnosed HCV cases in Hawaii. Treatment is
      concentrated among twelve physicians and aggressive case finding may overwhelm
      present resources. More primary care physicians need to participate in the
      detection and management of HCV.

PMID- 11467009
TI  - Chronic hepatitis C caused by a virus--fiction or for real?

PMID- 11467010
TI  - Surgical extirpation of a chest wall desmoid tumor: a case report.
AB  - A case is described of an anterior chest wall desmoid tumor in a 20-year-old
      Micronesian male that had been previously incompletely resected one year prior to
      presentation. A radical chest wall resection was performed with reconstruction
      accomplished using a gortex patch and latissimus dorsi myocutaneous flap. The
      patient developed a massive local recurrence within eight months following
      surgery. This report illustrates the local aggressiveness of these benign tumors.
      A historical perspective, etiology, and treatment principles are discussed.

PMID- 11467011
TI  - A 54-year-old man with arthritis and diarrhea.

PMID- 11467012
TI  - Availability of clinical trials for Hawaii cancer patients.

PMID- 11467013
TI  - PHLS primary care consultation--infectious disease and primary care research and
      service development priorities.
AB  - In 1999 for the first time the PHLS undertook a questionnaire survey of general
      practitioners' views of the burden of infectious disease and the priorities for
      research and development of infectious disease services within the PHLS. Three
      hundred and seventy-one (38%) of 979 questionnaires mailed to chairs of primary
      care groups in England, and general practitioners in research networks, were
      returned. Service areas: computer transfer of laboratory results was considered
      of greatest priority. Guidance on antibiotic usage, guidance on infectious
      diseases and education for general practitioners were ranked two, three and four.
      Burden of infectious disease in primary care: upper respiratory tract infections,
      tonsillitis/pharyngitis, otitis media/externa and acute cough were placed one,
      three, four and seven respectively. Urinary tract infections were ranked second
      and dyspepsia/Helicobacter pylori fifth. Leg ulcers, diarrhoea, genital chlamydia
      infection and vaginal discharge were other diseases considered to cause a large
      burden of ill-health. Genital chlamydia, tuberculosis, Helicobacter pylori and
      meningococci were ranked one, two, three, and five in the NHS opportunity to
      affect the burden of ill-health. Priorities for improvements to diagnostic tests,
      evidence on which to base treatment and guidance: chronic fatigue/ME was ranked
      top in these areas. The other top ten syndromes ranked in order were genital
      chlamydia infections, antibiotic resistance surveillance, vaginal discharge, leg
      ulcers, sinusitis, otitis media/externa, dyspepsia/Helicobacter pylori,
      Creutzfeld Jacob Disease, and tonsillitis. This consultation exercise has
      highlighted broad areas for future PHLS involvement in primary care. In order to
      make progress, further consultation is needed with groups of GPs, and other
      relevant bodies. Particularly for the areas ranked in the top ten, the type of
      further PHLS involvement needs to be defined. For some syndromes (chronic fatigue
      and leg ulcers) this may be writing guidance and for others (respiratory tract
      infections) more treatment trials are required. The purposes and possible methods
      of communicable disease surveillance in general practice should be the subject of
      additional consultation.

PMID- 11467014
TI  - The OVCD, and what's emerging in England and Wales.

PMID- 11467015
TI  - The national CD4 surveillance scheme for England and Wales.
AB  - This paper describes a national surveillance scheme, began in 1995, designed to
      monitor immunosuppression associated with HIV infection in adults in England and
      Wales. Currently 60 out of 64 (94%) laboratories performing CD4 cell counts
      participate in the scheme. The database contains over 42,000 patient records with
      over 300,000 counts, taken between April 1984 and March 2000. Approximately half
      of the patient records in the CD4 database match with patient records in the UK
      database of diagnosed HIV infections; a large proportion of the unmatched
      patients in the CD4 database may not be HIV-infected. Close to 50% of both men
      who have sex with men and injecting drug users and two-thirds of those who
      acquired their infection heterosexually had CD4 cell counts below 350 cells/mm3
      at the time of HIV diagnosis. The National CD4 Surveillance Scheme provides
      important information regarding the epidemiology of HIV infection such as the
      changes in patterns of early and late diagnosis. It should continue to be used in
      conjunction with the other HIV surveillance systems to present as complete a
      picture of the epidemic as possible.

PMID- 11467016
TI  - Test of HIV incidence shows continuing HIV transmission in homosexual/bisexual
      men in England and Wales.
AB  - It has been suggested that HIV incidence will decrease with the increased use of
      antiretroviral Therapy (ART) in HIV infected homosexual/bisexual men. HIV
      incidence was measured using a sensitive/less sensitive assay technique, at a
      time when combination ART was widespread. The Serological Testing Algorithm for
      Recent HIV Seroconversion (STARHS)13 technique was applied to syphilis test
      specimens collected from homosexual/bisexual men attending 15 sexually
      transmitted infections (STI) clinics which participated in an unlinked anonymous
      serosurvey of HIV infection during 1998. The HIV incidence rate was adjusted to
      compensate for patients who had a repeat syphilis test within the same year.
      Leftover syphilis test sera from 6202 men had been unlinked and anonymised, of
      which 415 were HIV positive. Sera from 412 (99.3%) patients were available. The
      STARHS assay showed 62 to have been recently infected with HIV (approximately in
      the last four months), giving an incidence of 3.33% per annum (95% CI: 2.06%
      5.27%). The highest incidence was seen in those aged 35-44 years. About 46% of
      all HIV-infected homosexual/bisexual men were probably receiving combination ART
      at this time. If 10% of those on treatment were misclassified as recent
      infections the incidence would have been 2.58% per annum (95% CI: 1.53%-4.24%).
      In homosexual/bisexual men having syphilis tests at STI clinics in the UK during
      1998 the incidence of HIV infection was between two and three per hundred per
      year. Treatment with combination ART of almost a half of homosexual/bisexual men
      who are HIV infected in the population is compatible with appreciable continuing
      HIV transmission among those at high behavioural risk. Public health surveillance
      systems for those at high risk for HIV infection should, as soon as possible,
      incorporate the STARHS methodology for monitoring recent HIV incidence.

PMID- 11467017
TI  - Potential for hepatitis C transmission among non-needle/syringe sharing Sheffield
      drug injectors through the sharing of drug preparation paraphernalia.
AB  - This study aimed to investigate possible means by which hepatitis C virus (HCV)
      might be transmitted between drug injecting individuals without the sharing of
      needles and syringes. A questionnaire-based survey of 143 (out of 287) attendees
      was conducted at an Infectious Diseases Unit-based HCV clinic. Those patients
      (all of whom were positive for antibodies to HCV) who asked about risk activities
      and those that admitted to a history of recreational drug injecting were
      questioned in detail about their past and current drug preparation practices. Ten
      per cent denied any history of needle and/or syringe sharing and had no other
      apparent source of their HCV infection, but instead admitted to having shared
      drug preparation eqiupment. The existence among drug injectors of such practices
      with the potential to transmit blood borne viruses is important as it may explain
      how HCV, which is capable of being spread via very small quantities of blood, can
      be passed between drug injecting individuals who might otherwise never come into
      contact with another drug injector's blood. Clinical and public health messages
      regarding the prevention of the spread of HCV may need to be revised and
      strengthened.

PMID- 11467018
TI  - Surveillance of CD4 counts in known HIV-infected people--a paradigm for the era
      of highly active antiretroviral therapy.

PMID- 11467019
TI  - Pneumococcal vaccination: opinion of general practitioners and hospital doctors
      in Scotland, 1999-2000.
AB  - A cross sectional survey by postal questionnaire was carried out to examine
      general practitioners' (GPs) and hospital doctors' (HDs) knowledge, attitudes and
      practice (KAP) with regard to pneumococcal vaccination in primary and hospital
      care in Scotland. Most GPs and HDs considered patients with chronic medical
      conditions, as recommended by the Department of Health (DoH), to be candidates
      for pneumococcal vaccination. Although the DoH does not currently recommend the
      vaccine for all the elderly, 47% of GPs and 46% of HDs reported that the vaccine
      should be given to this group. GPs (61-85%) and HDs (48-55%) indicated that they
      considered the vaccine to be safe and effective. The acceptance of pneumococcal
      vaccine was much lower than for influenza vaccine however, and 79% of HDs and 17%
      of GPs had never used the vaccine. Documented policies (with or without set
      targets) for pneumococcal vaccine existed in only 14% of general practice and 3%
      of hospital settings. Over 70% of respondents indicated that GPs should take
      responsibility for pneumococcal vaccination. The main sources of knowledge about
      pneumococcal vaccines were stated to be discussion with colleagues, review of
      medical literature, past experience, and the DoH recommendations. A clear
      immunisation policy and financial support for vaccination were identified as
      important strategies to improve pneumococcal vaccine coverage. Strategies
      directed toward these factors could enhance vaccine delivery and coverage of
      vaccine in high-risk individuals.

PMID- 11467020
TI  - Ice machines--an audit of their use in clinical practice.
AB  - Ice is used in clinical settings for a variety of reasons and ice making machines
      have been implicated in outbreaks of nosocomial infection. An audit was
      undertaken to investigate the routine local and strategic management and
      maintenance of ice machines in clinical settings. The results highlighted the
      need to implement local policies for the purchase, use and maintenance of such
      machines.

PMID- 11467021
TI  - The pros and cons of using hepatitis A vaccine to control outbreaks.

PMID- 11467022
TI  - Microbiological examination of ready-to-eat quiche from retail establishments in
      the United Kingdom.
AB  - A microbiological study of ready-to-eat quiche from retail establishments was
      undertaken to identify risk factors in the production, storage and handling of
      quiche and to establish their effect on microbiological quality. Examination of
      cold ready-to-eat quiche from supermarket and other delicatessens, bakers,
      butchers, cafes, sandwich bars and other retail premises revealed that most (2354
      of 2513; 94%) were of acceptable quality; 157 samples (6%) were of unsatisfactory
      quality and two (< 1%) were unacceptable. Unsatisfactory results were mostly due
      to high aerobic colony counts. Unacceptable results were due to high levels (>
      10(4) cfu/g) of Escherichia coli in two samples. Salmonella spp. were not
      detected in any of the samples. Satisfactory microbiological quality of ready-to
      eat quiche was associated with premises that had management food hygiene training
      and hazard analysis in place. The microbiological quality of this food was also
      associated with premises type, quiche type, slicing and serving methods, and
      existing Local Authority Inspectors' Consumer at Risk scores.

PMID- 11467023
TI  - An outbreak of acute hepatitis B infection among injecting drug users in
      Inverclyde, Scotland.
AB  - This large outbreak of acute hepatitis B infection among injecting drug users
      (IDUs) was precipitated by an increase in injecting heroin use in Inverclyde in
      the West of Scotland, between 1997 and 1999. Ninety-two cases of hepatitis B
      infection in residents of Inverclyde were reported to Argyll and Clyde Health
      Board from January 1996 to December 1999. An investigation of risk factors found
      87% (80/92) of the cases were IDUs, of whom four-fifths were men. Fifty six per
      cent of cases were aged 20-29 years old and 12% were aged 16-19 years old.
      Further investigations among this close community of young and relatively
      inexperienced IDUs revealed that many admitted to sharing injecting equipment
      particularly spoons, water and filters. Only a minority had been using local
      needle exchange facilities in the area. After public consultation a second needle
      exchange was opened in 1998 staffed by a dedicated needle exchange development
      worker who has continued to develop harm reduction services locally.

PMID- 11467024
TI  - Invasive M-type 3 Streptococcus pyogenes affecting a family and a residential
      home.
AB  - This paper describes the first recognised United Kingdom outbreak of M-type 3
      streptococci for 12 years. Four epidemiologically-linked invasive infections
      occurred in a residential home in northern England over two weeks. The index
      patient was admitted from home with necrotising fasciitis of the leg. Infection
      was subsequently detected in her husband (fatal pneumonia) another resident
      (fatal pneumonia) and a member of the care staff (parapharyngeal abscess).
      Screening of staff and residents in the home did not reveal any further infection
      or carriage. There is a substantial risk of serious secondary infection amongst
      the contacts of a patient with invasive Streptococcus pyogenes infection.
      Guidance is lacking, but needed, on the advisability of chemoprophylaxis in these
      circumstances.

PMID- 11467025
TI  - An outbreak of viral gastro-enteritis at a charity function.
AB  - One hundred and thirty-eight people of 431 who attended a charity function fell
      ill with gastro-enteritis mainly between 12 and 72 hours later. Three people were
      ill at the event, and a further three became ill within two hours of the event. A
      cohort study undertaken using a postal questionnaire showed that illness was
      statistically associated with having eaten cream, mints, or profiteroles. The
      duration of illness ranged from two to 120 hours, with a median of 48 hours.
      Twenty-three of the cases sent a stool sample to the laboratory. Six of these
      were taken to the laboratory within three days of the onset of illness and
      examined for bacteria before being sent for virological examination by electron
      microscopy (EM) and polymerase chain reaction (PCR). All six were positive for
      small round structured virus (SRSV) on PCR, and negative on EM. The illness was
      likely to have been transmitted both by foodborne transmission and person to
      person spread at the event.

PMID- 11467026
TI  - Failure to vaccinate current injecting drug users against hepatitis B in England
      and Wales.
AB  - In most industrialised countries the elimination of hepatitis B infection is
      highly reliant on effective vaccine delivery to injecting drug users. This paper
      highlights the very poor vaccine coverage achieved in England and Wales in the
      ten years since this problem was officially recognised and targeted. This is
      despite the existence of a comprehensive and well-utilised network of specialist
      services for injecting drug users.

PMID- 11467027
TI  - DNA tags.
AB  - Amplification methods could be used to develop tests so that very small protein
      amounts could be detected. A piece of DNA--a DNA tag--could be coupled to an
      antibody, and this could then be used to detect a protein antigen by
      amplification of the DNA tag.

PMID- 11467028
TI  - Evaluations of kits and equipment in public health laboratories.

PMID- 11467029
TI  - Health and safety and the Human Rights Act 1998.
AB  - The Human Rights Act 1998 came into effect on 2 October 2000. The list of human
      rights now embodied in United Kingdom law reflects the ideas and values of our
      changing and developing society. As a dynamic document the act has parallels with
      the ideals found in health and safety law. This article looks at the act and
      considers its implications for employers with regard to existing health and
      safety law.

PMID- 11467030
TI  - PHLS overview of communicable diseases 1999.
AB  - Every other year since 1995 the Public Health Laboratory Service has undertaken a
      consultation exercise to identify communicable diseases of high public health
      priority. The purpose of identifying disease priorities is to guide rational and
      transparent service planning and resource allocation. Also, the process aims to
      ensure a customer sensitive service. This paper presents the results of the
      priority setting exercise undertaken in 1999. A postal questionnaire was sent to
      1130 key professionals involved in communicable disease control in the United
      Kingdom. Respondents were asked to assess the relative priority of 61
      communicable diseases and to identify priority areas of work associated with
      these diseases. Five criteria were used to assess relative priority. The five
      criteria were; present burden of ill-health, social and economic impact,
      potential threat to health, health gain opportunity and public concern and
      confidence. For each disease, respondents were asked to score the importance of
      each criterion. Forty six percent of participants (518/1130) returned completed
      questionnaires. There was no significant difference in response rate by
      professional group. Based on the scores assigned to each of the five criteria,
      the relative priority of 61 communicable diseases has been established. The top
      ten diseases in descending order of priority are, HIV/AIDS, meningococcal
      diseases, Chlamydia trachomatis, influenza, tuberculosis, E. coli O157,
      Methicillin resistant Staphylococcus aureus, salmonellosis, transmissible
      spongiform encephalopathies and Helicobacter pylori. The opinion of a large
      number of health care professionals has been used to establish a priority rank
      for a wide range of communicable diseases. This work provides planners and policy
      makers with a synthesis of current professional opinion that can be used as a
      foundation for making decisions on service developments.

PMID- 11467031
TI  - Elder abuse and neglect in medicine and law. The need for reform.

PMID- 11467032
TI  - Access to health care in the United States. A symposium overview and commentary.

PMID- 11467033
TI  - Universal health care coverage. A two-front war.

PMID- 11467034
TI  - Access to health care. It's not rocket science--it's tougher.

PMID- 11467035
TI  - Health insurance and health access. Reengineering local safety nets.

PMID- 11467036
TI  - Latex gloves. Medical-legal issues for health care professionals.

PMID- 11467037
TI  - Medical residents. Should they be held to a different standard of care?

PMID- 11467038
TI  - Lipid disorders in patients with type 2 diabetes. Meeting the challenges of
      early, aggressive treatment.
AB  - Because patients with type 2 diabetes are at high risk for cardiovascular events,
      lipid abnormalities in these patients should be aggressively and efficiently
      treated. What is the rationale behind such an approach, and what are the goals of
      therapy? Dr Marcus addresses these questions and provides up-to-date
      recommendations for lipid-lowering treatment.

PMID- 11467039
TI  - Complications of flexible sigmoidoscopy?

PMID- 11467040
TI  - Urinary tract infections.

PMID- 11467041
TI  - Zoonotic infections from pets. Understanding the risks and treatment.
AB  - As much as we hate to admit it, even the gentlest of our friendly pets can harbor
      harmful pathogens, and although the fact is not widely known, pet-associated
      infections can significantly affect the health of humans. In this article, Dr
      Morrison focuses on pets and their accompanying potential zoonoses, outlining how
      these diseases can be transmitted to humans and how the infections are treated.
      Special attention is paid to rabies and toxoplasmosis, which have attained
      particular notoriety over time.

PMID- 11467042
TI  - Eradication of ectoparasites in children. How to treat infestations of lice,
      scabies, and chiggers.
AB  - Infestations of head lice, body lice, scabies, and chiggers are common causes of
      rash and pruritus in children. Concern has arisen about development of resistance
      to often-used treatments, but a comprehensive approach to eradication is usually
      very effective. In this article, Dr Potts describes the presentation of
      ectoparasites and discusses conservative treatment and the safe use of
      pediculicides.

PMID- 11467043
TI  - Preparing to meet foreign bugs. Travel, immigration, and international adoptions
      require special precautions.
AB  - As the world's population becomes increasingly mobile, children are more likely
      to be exposed to exotic and troublesome pathogens. These exposures raise concerns
      about protecting not only kids but the general population as well. In this
      article, Dr Petersen presents ways to avoid illness in children who travel to
      other parts of the world. She also discusses concerns about communicable disease
      as it relates to immigration or adoption of foreign-born children, especially
      those from developing nations.

PMID- 11467044
TI  - Making sense of outpatient pharmacy management. How to control pharmacy costs
      while delivering quality care.
AB  - Pharmacy brings together some of the major themes ushering US healthcare into the
      21st century: concern about iatrogenesis, patient consumerism, resurgence of
      healthcare costs, and wide disparity in access to flourishing technology.

PMID- 11467045
TI  - Fungal skin infections in children. New developments and treatments.
AB  - Recognizing the common manifestations of pediatric fungal infections is a key
      part of any primary care practice. Of paramount importance is the clinical acumen
      of the physician. In this article, Drs Berg and Erickson discuss several types of
      fungal infections in children, identify tools for diagnosis, and outline the most
      effective options for treatment. Newer "off-label" therapies are also examined.

PMID- 11467046
TI  - Approaches to vitamin B12 deficiency. Early treatment may prevent devastating
      complications.
AB  - Vitamin B12 deficiency is a common problem that affects the general population
      and the elderly in particular. Persons with the deficiency may be asymptomatic or
      may have hematologic or neuropsychiatric signs and symptoms. If the disorder is
      untreated, complications may cause significant morbidity. In this article, Drs
      Dharmarajan and Norkus discuss approaches to screening and diagnosis as well as
      the nontoxic, low-cost treatments now available.

PMID- 11467047
TI  - Motor neuron disease: classification and nomenclature.
AB  - The classification and nomenclature of motor neuron disease, whether sporadic or
      familial, is confused. For example, both the sporadic and familial motor neuron
      diseases are phenotypically heterogeneous and, in familial ALS, phenotypic
      heterogeneity correlates only weakly with different underlying mutations in the
      SOD1 gene. We propose a classification which is based on underlying causative
      mechanisms, where these are known, but which also recognizes different clinical
      phenotypes when the cause is unknown. This classification is flexible, and allows
      reattribution of clinical syndromes when their causation is understood. Currently
      uncertain associations--for example, a possible association of ALS with cancer-
      are given tentative recognition in this classification. In addition, this new
      classification recognizes geographical clustering and descriptions of unusual
      motor neuron disorder phenotypes of unknown origin in different parts of the
      world.

PMID- 11467048
TI  - GDNF is trophic for mouse motoneurons that express a mutant superoxide dismutase
      (SOD-1) gene.
AB  - BACKGROUND AND METHODS: An in vitro system of motoneurons was established from
      mice carrying a transgene for a human superoxide dismutase-1 (SOD-1) with a
      gly93ala mutation that has been linked to familial amyotrophic lateral sclerosis
      (FALS). These cultures were characterized and used to compare the effects of
      glial cell line-derived neurotrophic factor (GDNF) on motoneurons expressing the
      mutant gene with those on normal motoneurons. RESULTS: Recombinant human GDNF
      (100 ng/ml) significantly promoted the survival of a subpopulation of choline
      acetyltransferase (ChAT)-immunoreactive motoneurons that were also immunoreactive
      for the homeoprotein islet-1 in cultures from both wild type and mutant SOD-1
      mice. However, GDNF did not increase the total number of ChAT-immunoreactive
      neurons in cultures from either wild type or transgenic mice. A distinct
      subpopulation of islet-1-immunoreactive motoneurons characterized by a soma 3 1/2
      times larger and a ten-fold increase in neurite length was observed exclusively
      in GDNF-treated cultures. In cultures from mutant SOD-1 mice, there were 3 1/2
      times as many motoneurons of this subpopulation as in wild type cultures at 6
      days in vitro. In addition, this subpopulation of neurons survived for 10 days in
      vitro, the longest time point studied, in culture from mutant SOD-1 mice, but not
      in cultures from wild type mice. This subpopulation was also present at 6 days in
      vitro in cultures from mutant SOD-1 mice that received GDNF at 3 days in vitro
      instead of at the time of plating, suggesting that GDNF promotes the
      differentiation of these neurons. CONCLUSION: Our observations suggest that the
      expression of a mutant SOD-1 gene, as occurs in familial ALS, does not compromise
      the trophic effects of GDNF on motoneuron survival, but may affect the
      development of motoneurons.

PMID- 11467049
TI  - Quantitative proton magnetic resonance spectroscopy of the subcortical white
      matter in motor neuron disease.
AB  - BACKGROUND: Using proton magnetic resonance spectroscopy, the authors have
      previously demonstrated a reduction in the N-acetyl aspartate/(creatine and
      phosphocreatine) (NAA/(Cr + PCr)) ratio in the motor region in bulbar-onset MND
      patients, attributed to neuronal loss or dysfunction leading to a reduction in
      NAA. We have expanded this analysis to evaluate absolute concentrations of NAA,
      (Cr + PCr) and choline-containing compounds (Cho) in the subcortical white matter
      in the motor region in 16 MND patients (8 with bulbar onset and 8 with limb
      onset) and 8 healthy, age-matched controls. METHODS: Single voxel 1H-MRS was
      performed using a PRESS localization sequence. Metabolite concentrations were
      determined using the water signal as an internal standard. RESULTS: We found no
      differences in the concentrations of NAA ([NAA]), (Cr + PCr) ([Cr + PCr]) or Cho
      ([Cho]) in the motor region on comparing the total MND group and controls (P >
      0.3). No difference was found in [NAA] in the bulbar-onset group compared with
      the limb-onset group (P = 0.70), but [Cr + PCr] was significantly higher in the
      bulbar-onset group (P = 0.04). CONCLUSIONS: Our results suggest that [Cr + PCr]
      may be affected by the pathological process in MND, and this should be considered
      in the interpretation of metabolite peak area ratios. The elevated (Cr + PCr) may
      represent gliosis in the subcortical white matter in the motor cortex region.

PMID- 11467050
TI  - Motor unit number estimate: has its time arrived?

PMID- 11467051
TI  - Classification of ALS--do we know enough?

PMID- 11467052
TI  - GDNF is trophic for mouse motoneurons that express a mutant superoxide dismutase
      (SOD1) gene.

PMID- 11467053
TI  - Motor unit number estimation, ALS and clinical trials.
AB  - Motor unit number estimation (MUNE) techniques have evolved substantially over
      the past decade and have been applied, with increasing frequency, to the study of
      amyotrophic lateral sclerosis (ALS). As major clinical therapeutic trials in
      motor neuron disease continue to appear, the need for a clear quantitative method
      of following motor unit physiology in the living subject grows ever more
      pressing. In this article, we review the major modern techniques of MUNE and the
      data supporting their reproducibility and utility in patients with ALS, with
      particular attention to their role in evaluating the efficacy of new therapeutic
      interventions.

PMID- 11467054
TI  - Current status of SOD1 mutations in familial amyotrophic lateral sclerosis.
AB  - Twenty percent of cases of familial amyotrophic lateral sclerosis (FALS) have
      identifiable mutations in the gene for Cu, Zn superoxide dismutase (SOD1) located
      on the long arm of chromosome 21. SOD1 mutations are thought to cause a yet
      unknown toxic gain of function resulting in motor neuron damage. Seventy-one
      mutations, located in all five exons of SOD1, have been reported. Identified
      mutations are predominantly heterozygous mis-sense mutations, although rare
      nonsense mutations, deletions, and insertions exist. While gene dosage has an
      effect on the age of onset, genotoype/phenotype correlation is better defined for
      progression of symptoms than for disease onset.

PMID- 11467055
TI  - Nutritional assessment and survival in ALS patients.
AB  - Malnutrition, present in 16-50% of ALS patients, is an independent prognostic
      factor for worsened survival. It is caused primarily by swallowing dysfunction,
      resulting from involvement of the lower sets of cranial nerves, but
      hypermetabolism is also implicated. Malnutrition itself can produce neuromuscular
      weakness and adversely affect patients' quality of life, thereby creating a
      vicious circle. The nutritional status of ALS patients can be assessed with
      dietary review and measurements of weight (W) and height (H). A body mass index
      (BMI = W/H2) below 18.5-20 kg/m2 indicates a state of malnutrition. Dietary
      counselling is important, but rapidly becomes insufficient, particularly in
      bulbar-onset ALS, where enteral nutritional support is then necessary.
      Percutaneous endoscopic gastrostomy tube placement is well tolerated, and
      provides more efficient enteral nutrition than nasogastric tube feeding. Enteral
      nutrition support can improve the respiratory status of ALS patients. The effect
      on survival remains to be confirmed.

PMID- 11467056
TI  - Neuropathology of amyotrophic lateral sclerosis with extra-motor system
      degeneration: characteristics and differences in the molecular pathology between
      ALS with dementia and Guamanian ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is classified into distinct subtypes mainly
      based on clinicopathological features, in addition to epidemiologic and genetic
      backgrounds. In addition to sporadic ALS with classical pathology,
      characteristics in the clinical features, in the histological findings and their
      topographical distribution, and in the molecular pathology, especially the
      intracytoplasmic neuronal inclusions, enable us to identify the following
      subtypes: ALS with dementia (ALS-D), ALS in the Western Pacific, ALS with multi
      system degeneration, familial ALS, and superoxide dismutase 1-linked ALS. These
      subtypes not infrequently exhibit various types of extra-motor system
      degeneration, and even multi-system pathology. Some of the subtypes (for instance
      ALS-D or familial ALS) can be deduced, to a certain extent, from characteristic
      neuronal inclusions such as ALS-type ubiquitinated inclusions, Lewy body-like
      hyaline inclusions (LBHIs), or ubiquitinated intracytoplasmic neuronal inclusions
      as typically seen in the dentate fascia. The purpose of this article is to
      clarify the molecular pathogenesis of the cerebral cortex in ALS-D and Guamanian
      ALS and parkinsonism-dementia complex (PDC), in order to elucidate the
      relationship and distinction between these two subtypes. As indicated previously,
      investigations on ubiquitin-immunoreactivity in the hippocampus further support
      the view that the pathology of G-ALS/PDC may be that of a tau-related tangle
      disorder, whilst ALS-D has a feature of the motor neuron disease type
      frontotemporal dementia.

PMID- 11467070
TI  - So much research evidence, so little dissemination and uptake: mixing the useful
      with the pleasing.

PMID- 11467072
TI  - Applying the results of trials and systematic reviews to our individual patients.

PMID- 11467074
TI  - Targets for steroid hormone mediated actions of periodontal pathogens, cytokines
      and therapeutic agents: some implications on tissue turnover in the periodontium.
AB  - This review attempts to encapsulate the relevance of steroid hormone action in
      the periodontal tissues, during inflammation, repair and in response to current
      treatment modalities. Periodontal pathogens metabolise steroid hormones which
      could contribute to their nutritional requirements and host evasion mechanisms,
      by forming capsular proteins; their culture supernatants stimulate the synthesis
      of physiologically active steroid hormones by fibroblasts, which aid inflammatory
      repair. The functions of glucocorticoids, androgens, oestrogen and progesterone
      on connective tissue and bone, are applicable to the periodontium, being target
      tissue. This results in physiological effects on these tissues, during puberty,
      the menstrual cycle, pregnancy and the menopause. The effects of oral
      contraceptives and hormone replacement therapy on the periodontium have focused
      interest in the relationship between sex steroid hormones and periodontal health.
      Receptor expression and the role of the specific enzyme inhibitors, such as the
      anti-androgen finasteride and the anti-oestrogen tamoxifen, confirm target tissue
      activity for steroid hormones in the periodontium. The pro-anabolic and anti
      inflammatory actions of tetracyclines, are an intriguing model for hormone
      mediated pathways of action. The effects of the specific alkaline phosphatase
      inhibitor levamisole on matrix turnover are linked to steroid hormone action,
      with direct implications on the healing periodontium. Drugs which contribute to
      gingival overgrowth are an interesting model, for explanation of an exaggerated
      'scar tissue' response mediated by hormones, cytokines and a variety of enzyme
      systems. Cell dynamics of the periodontium plays an important role in co
      ordinating the diverse interactions between steroid hormones and therapeutic
      agents.

PMID- 11467075
TI  - The use of TNF family ligands and receptors and agents which modify their
      interaction as therapeutic agents.
AB  - The earlier known TNF family cytokines have fairly wide physiological actions,
      mainly in inflammation and immune responses. It is now considered feasible to
      develop these large proteins themselves as therapeutic agents, but in addition,
      modular organisation of structures of biological proteins, and the identification
      of localised ligand-receptor interaction sites, allow rational design of smaller,
      preferably nonpeptide molecules which interfere with these protein:protein
      interactions. Neutralising anti-TNF antibodies and soluble TNF receptor
      preparations were shown to have striking anti-inflammatory activities in clinical
      studies, particularly in rheumatoid arthritis. As the TNF beta:TNFR1 co-crystal
      structure was the first in the family to be solved, rational drug design based on
      the ligand:receptor interaction sites is more advanced. Ligand mutations and a
      peptide sequence from TNF-alpha have given useful information regarding ligand
      receptor interactions. Small peptide sequences from TNFR I which interact with
      the ligand have shown some activity in blocking the biological actions of TNF.
      The physiological activities of several recently-discovered ligands are more
      limited, giving possibilities for selective treatment of several diseases. For
      example, TRAIL can induce apoptosis in a wide range of tumour cells with little
      effects on normal tissues, both in vitro and in vivo. The co-crystal structure of
      TRAIL with one of its signalling receptors TRAILR 2 has been solved, opening the
      way to rational small molecule drug design. TRANCE (RANKligand) has modulatory
      effects on the dendritic cell:T cell interaction in immune responses. However, it
      plays a more major controlling role in the development of osteoclasts and their
      bone resorbing activity. In this way, it is a very interesting drug development
      target for the treatment of bone disorders such as osteoporosis. A recombinant
      secreted inhibitory receptor, osteoprotegerin (OPG), is in Phase 1 clinical trial
      for the treatment of hyper-resorptive bone diseases. However, OPG also blocks
      TRAIL and may not be sufficiently specific in long term therapy, but it is hoped
      that inhibitors of the interaction of TRANCE and its specific signalling
      receptor, RANK, can be rationally designed.

PMID- 11467076
TI  - The Src homology-2 domains (SH2 domains) of the protein tyrosine kinase p56lck:
      structure, mechanism and drug design.
AB  - Src homology 2 (SH2) domains are found in many intercellular signal-transduction
      proteins which bind phosphotyrosine containing polypeptide sequences with high
      affinity and specificity and are considered potential targets for drug discovery.
      The protein p56lck is a member of the family of Src tyrosine kinase. The SH2
      domain is thought to be responsible for the recruitment and regulation of p56lck
      kinase activity. There have been enormous efforts in the development of SH2
      domain inhibitors for diseases such as cancer, osteoporosis and other diseases.
      This review focuses on current understanding of SH2 domain structure, mechanism
      and drug discovery with an emphasis on p56lck SH2 domain. A potential impact of
      the accumulated crystallographic effort on the development of methods for
      structure-based drug design is briefly addressed.

PMID- 11467077
TI  - The ubiquitin-dependent proteolytic system and other potential targets for the
      modulation of nuclear factor-kB (NF-kB).
AB  - Nuclear Factor-kB (NF-kB), is a transcription factor composed of dimeric
      complexes of p50 (NF-kB1) or p52 (NF-kB2) usually associated with members of the
      Rel family (p65, c-Rel, Rel B) which have potent transactivation domains.
      Different combinations of NF-kB/Rel proteins bind distinct kB sites to regulate
      the transcription of different genes. In resting cells NF-kB resides in the
      cytoplasm in inactive form, complexed to members of a family of inhibitory
      proteins referred to as IkB. The bound IkB masks the NF-kB nuclear localization
      signal and thereby inhibits its nuclear transport. NF-kB can be activated by a
      variety of signals relevant to pathophysiology including inflammatory cytokines
      and bacterial lipopolysaccharides (LPS) as well as oxidative and fluid mechanical
      stress. Upon activation by these stimuli, IkB is phosphorylated and subsequently
      degraded. Phosphorylation targets IkB for ubiquitination and degradation by the
      26S proteasome thus leading to NF-kB nuclear translocation. The same proteolytic
      pathway is involved in the processing of the p105 and p100 precursors to generate
      mature p50 and p52 subunits, respectively. Once in the nucleus, NF-kB is able to
      regulate the expression of many genes involved in the immune and inflammatory
      responses (i.e. inflammatory cytokines and adhesion molecules). Thus, new
      approaches to modulating NF-kB activation, and as a consequence inflammatory or
      metastatic processes, may take advantage of the selectivity of the ubiquitination
      and ATP-dependent proteolytic processes leading to IkB turnover. This review will
      analyze the current strategies aimed at interfering with NF-kB activation and
      will consider the ubiquitination system as a new selective target for the
      development of new anti-inflammatory therapies.

PMID- 11467078
TI  - Current status of the cytosolic sulfotransferases in the metabolic activation of
      promutagens and procarcinogens.
AB  - Cytosolic sulfotransferases (SULT) catalyze the sulfation of structurally diverse
      drugs, endogenous compounds and xenobiotics. These reactions involve the transfer
      of a sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the
      hydroxyl/amino groups of acceptor molecules. Although sulfate conjugation is
      generally considered as a detoxication pathway producing more water-soluble and
      often less toxic metabolites, sulfation of certain classes of compounds produce
      sufficiently electrophilic metabolites that can covalently bind to cellular
      macromolecules, DNA and RNA. The important roles of electrophilic sulfate ester
      metabolites in the metabolic activation, mutagenicity and ultimate
      carcinogenicity of many xenobiotics have been considerably elucidated. Examples
      include the class of hydroxymethyl polycyclic aromatic hydrocarbons, allylic
      alcohols, N-hydroxy derivatives of carcinogenic arylamines and heterocyclic
      amines. Results obtained by many scientists during the last two decade correlate
      with a hypothesis that electrophilic sulfate esters may be the major ultimate
      carcinogenic forms of many, if not most, procarcinogens derived from
      benzylic/allylic alcohols and hydroxy arylamines. Careful analysis of these
      results suggest that the activities of human hydroxysteroid sulfotransferase
      (hHST), and a related form in rat liver, rat hydroxysteroid sulfotransferase a
      (STa), as well as aryl sulfotransferases both from rat and human liver, account
      for a substantial portion of the activation of benzylic/allylic alcohols in these
      species. Moreover, aryl sulfotransferases have also been indicated as the
      responsible SULT family in the bioactivation of hydroxy arylamines in the liver
      of different species including human. Molecular cloning of the individual
      sulfotransferases and expression of these individual forms in heterologous
      expression systems have allowed us to better understand the role of SULTs in the
      bioactivation of different procarcinogens and the form of sulfotransferase
      involved in their bioactivation. Additional structure-activity studies with
      homogeneous forms of rat liver STa and AST IV have also yielded comparative
      insight into some of the parameters important in recognition of substrates and
      inhibitors by these enzymes.

PMID- 11467079
TI  - Effective prodrug liposome and conversion to active metabolite.
AB  - Some antitumor agents encapsulated in liposomes have been used clinically.
      However, the usefulness of liposomes is limited to the liposomalization of active
      compounds. Irinotecan hydrochloride (CPT-11) is a prodrug of closed lactone ring
      form of SN-38, which is an active metabolite with antitumor and side toxicity.
      The plasma concentrations of closed CPT-11 and SN-38 increased with the
      liposomalization, and their blood circulation was prolonged by the
      polyethyleneglycol (PEG) modification. The antitumor activity of CPT-11 increased
      due to the elevated tumor distribution of closed CPT-11 and SN-38 levels by the
      PEG-modified liposomes. In the tumor, CPT-11 was converted to SN-38. Thus, it is
      considered that passive targeting to the tumor by liposomalization elevated the
      SN-38 level in the tumor especially and increased the antitumor activity of CPT
      11. The closed/total ratio of SN-38 in the tumors of the liposomes group was
      greater than that of the CPT-11 solution group. Namely, SN-38 was thought to be
      generated in intact liposomes containing CPT-11. The generation of SN-38 in the
      liposomal membrane was shown after the incubation of liposome containing CPT-11
      with carboxylesterase. It is therefore considered that part of CPT-11 is
      converted to SN-38 in intact liposomes. Furthermore, intestinal disorder, a side
      toxicity of CPT-11, decreased to depend on the closed SN-38 concentrations in the
      bile by liposomalization. Although the liposomes induce the improved tissue
      distribution of the prodrug, the tissue distribution of active metabolites do not
      always improve. However, CPT-11 entrapped liposome was useful.

PMID- 11467080
TI  - Xenobiotic-CoA ligases: kinetic and molecular characterization.
AB  - This review focuses primarily on the mammalian medium and long-chain fatty acid
      coenzyme A ligases that have been implicated in the metabolism of xenobiotic
      carboxylic acids such as pesticides, arylpropionate non steroidal anti
      inflammatory drugs and the hypolipidaemic clofibrate and its congeners. Evidence
      of multiplicity of mitochondrial and microsomal enzymes and their respective
      substrate/inhibitor profiles are discussed. For completeness, where appropriate,
      details of non-substrate inhibitors have also been included. Although knowledge
      is limited at present with respect to the medium-chain enzymes, aspects of
      regulation particularly the in vivo, in vitro role of peroxisome proliferators
      and current knowledge of the molecular biology of the long-chain fatty acid CoA
      ligase superfamily are documented. Additionally, alignment of thirteen cloned
      mammalian fatty acid CoA ligases using criteria established for the CYP and UGT
      superfamilies has enabled construction of a phylogenetic tree that clearly
      defines three families. Catalytic data are still limited and the xenobiotic
      substrate/inhibitor profiles of the recombinant proteins are incomplete. Finally,
      with increasing recognition of the importance of fatty acyl-CoA esters as
      physiological regulators of cell function including gene expression, the review
      concludes with a discussion of the metabolic fate and toxicity of xenobiotic acyl
      CoA esters.

PMID- 11467081
TI  - Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds
      on cytochrome P450-dependent drug oxidation.
AB  - Cytochrome P450 (CYP) enzymes catalyse the oxidative conversion of drugs and
      other lipophilic compounds to hydrophilic metabolites. Thus, CYPs play a dominant
      role in the elimination of drugs from the body. Inhibitory interactions occur
      when drugs compete for oxidation by specific CYPs whereas certain drugs increase
      the capacity for oxidative biotransformation by inducing the synthesis of new
      CYPs. Methylenedioxyphenyl (MDP) compounds have been widely employed as
      commercially important pesticide synergists and a number of derivatives are found
      in oils and spices. MDP compounds are of considerable toxicological significance
      because of their capacity to inhibit and induce CYP enzymes in mammals; some
      derivatives produce neurotoxic and hepatotoxic effects. Although there are
      relatively few therapeutic agents of present clinical importance that possess the
      MDP structural feature, the synthesis and preclinical evaluation of such agents
      appears to be increasing. In the context of the existing literature surrounding
      MDP compounds it is noteworthy that these potential drugs also elicit significant
      modulatory effects on CYP activities in rat and human liver. These developments
      indicate the importance of understanding the chemical mechanisms by which MDPs
      interact with CYPs. Thus, the presence of the MDP structure may undermine the
      potential clinical value of new drugs.

PMID- 11467082
TI  - Turnover studies on cardiac natriuretic peptides: methodological,
      pathophysiological and therapeutical considerations.
AB  - Cardiac natriuretic peptide hormones (ANP and BNP) are synthesized and secreted
      by the heart, producing several biological effects, such as natriuresis,
      vasorelaxation, hypotension, and neuromodulation. Extensive studies conducted in
      both animals and humans have documented that cardiac natriuretic peptides (CNPs)
      are secreted into the circulatory system via the coronary sinus into the right
      atrium, and then rapidly degraded and removed from the blood by plasma proteases
      and specific clearance receptors. Usually, studies of CNPs kinetics have been
      carried out following an experimental protocol in which labeled or unlabeled
      hormone is administered (by constant infusion or bolus injection) and the
      corresponding concentration of the hormone is measured in peripheral venous
      blood. However, when a uniform intravascular concentration throughout artero
      venous vessels is lacking due to the very rapid clearance of the substance being
      studied (such as CNPs), the classical compartmental or none compartmental
      approach may not be suitable for interpreting the experimental data. In this
      case, a more physiological circulatory model, which does not assume a uniform
      intravascular distribution of the hormone and comprises several anatomo
      functional blocks arranged in a series and supplied by the same flow (cardiac
      output) should be adopted. Different experimental designs (infusion or bolus
      injection) as well as multiple sampling sites (aorta and pulmonary artery,
      inferior vena cava, femoral vein) were used in ANP kinetic studies. Using a
      circulatory approach, ANP has been demonstrated to be rapidly distributed and
      degraded; in healthy subjects about 50% of ANP secreted into the right atrium is
      extracted by the peripheral tissues during the first pass throughout the body.
      Since CNPs have important fluid-volume regulatory features, it has been
      postulated that they also play a key role in volume homeostasis in several
      pathophysiological states, such as congestive heart failure. Indeed, a markedly
      altered degradation and distribution of ANP in patients with cardiac failure who
      show a resistance to its natriuretic effects, even in those on the early stage of
      clinical disease, whose CNPs plasma levels are in the normal range, have been
      demonstrated. Recent studies indicate that some drugs, by inhibiting the
      degradation of CNPs by plasma proteases and can thus affect CNP kinetics, may be
      useful in the treatment of arterial hypertension and cardiac failure.

PMID- 11467083
TI  - [Psychotherapy--deficiency in medical curriculum?].

PMID- 11467084
TI  - Evidence versus experience?

PMID- 11467085
TI  - Falls in the elderly. II. Strategies for prevention.
AB  - In the companion paper, we have outlined how relevant risk factors for falls can
      be identified using a systematic approach. Once identified, the underlying
      diseases and pattern of (usually multiple) risk factors guides the design of an
      individually tailored intervention program. Such intervention programs follow one
      or more of the following goals: (a) to treat the underlying disease; (b) to
      reduce or even eliminate the number of falls; (c) to prevent or minimise the
      associated injuries; and (d) tertiary prevention of fall-related disability,
      including immobilisation, muscle weakness, reduced fitness, osteoporosis, fear of
      falling and mortality. The successful results of various intervention studies
      underscores that falls should be regarded as a potentially treatable disorder in
      elderly persons. Such knowledge is important for clinicians, which could apply
      prevention strategies to individual patients with risk factors that are strongly
      associated with falls. In addition, prevention is important for health policy
      makers who aim to reduce falls in the general population by reducing or
      eliminating commonly present risk factors (even if they are only weakly
      associated with falls).

PMID- 11467086
TI  - [Echocardiography in storage and neuromuscular disorders].
AB  - Storage disorders and neuromuscular disorders may lead to cardiac involvement
      which can be visualized by echocardiography. In storage disorders like
      hypothyroidism, haemochromatosis, amyloidosis, mucopolysaccharidosis and Fabry's
      disease, myocardial thickening and systolic dysfunction can be found. In
      amyloidosis, atrial enlargement and abnormal texture of the myocardium are
      additional findings. In advanced haemochromatosis all cardiac chambers may be
      dilated. In hypothyroidism and amyloidosis, a pericardial effusion can be
      present. In haemochromatosis and amyloidosis, a restrictive filling pattern may
      be detected using Doppler-sonography. Mucopolysaccharidosis and Gaucher's disease
      may lead to aortic and mitral stenosis. In neuromuscular disorders like
      glycogenosis, mitochondriopathy and myotonic dystrophy, myocardial thickening and
      systolic dysfunction are found, in spinal muscular atrophy myocardial thickening
      and in muscular dystrophy Becker/Duchenne systolic dysfunction. An abnormal
      myocardial texture may be present in glycogenosis, isolated left ventricular
      abnormal trabeculation (ILVAT) in mitochondriopathy, myotonic dystrophy and
      muscular dystrophy Becker/Duchenne. Using Doppler-sonography an impaired
      relaxation of the left ventricle may be detected in mitochondriopathy, myotonic
      dystrophy and spinal muscular atrophy. Most of these echocardiographic findings
      are unspecific and may be overlooked, especially if the storage or neuromuscular
      disorder is yet unknown. Establishing a correct diagnosis is important, since
      healing or functional improvement is possible in many of these disorders.

PMID- 11467087
TI  - Medical students' attitudes towards psychotherapy: an intervention-based pre-post
      comparison.
AB  - BACKGROUND: Despite a wealth of studies on medical students' attitudes towards
      psychiatry in general, little is known about their specific attitudes towards
      psychotherapy. There is no evidence on the flexibility of these attitudes in the
      context of a curriculum-implemented psychotherapy information session.
      OBJECTIVES: To assess medical students' attitudes towards psychotherapy and short
      term flexibility therein, with an introductory course on psychotherapy as the
      relevant intervention for this pre-post comparison. METHODS: A random sample of
      159 advanced medical students completed a short questionnaire before and after a
      short course on psychotherapy. The questionnaire consisted of indirect attitude
      measures towards psychotherapy (associations and connotations), a likelihood
      rating for future training in psychotherapy, a statement about one's most
      preferred medical specialty for one's future career, and basic demographics.
      RESULTS: Participants' pre-interventional connotations of psychotherapy were
      predominantly positive. In the pre-post comparison, more than one third of the
      connotation measures shifted substantially and favorably. Post-interventionally,
      participants' distinctive static word association style regarding psychotherapy
      was attenuated in favor of a more differentiated style and an enlarged field of
      associations. The data are suggestive of significant pre-interventional sex
      differences, with females holding more positive views towards psychotherapy and
      reporting a greater likelihood of future psychotherapeutic training. The data
      also suggest that the intervention acted differently upon the sexes. Likelihood
      ratings for future training in psychotherapy did not decline after the course,
      despite the fact that the cost and duration of training were mentioned in the
      course. CONCLUSIONS: Even minimal educational interventions can enhance medical
      students' predominantly positive attitudes towards psychotherapy. This finding
      calls for further implementation of psychotherapy-related material in medical
      curricula.

PMID- 11467088
TI  - Humoral mechanisms in the pathogenesis of postprandial hypotension in patients
      with essential hypertension.
AB  - OBJECTIVE: To examine the role of catecholamines and insulin in the development
      of postprandial hypotension (PPH) in hypertensive patients. PATIENTS: Forty
      patients with essential hypertension (25 men, 15 women, mean age 68 +/- 2 years).
      METHOD: Blood pressure and heart rate were recorded in all subjects immediately
      after a 1903 kJ test meal and at 15-minute intervals for up to 1 hour after the
      meal. At these time points, circulating levels of norepinephrine, epinephrine,
      dopamine and C-peptide were measured. RESULTS: Twenty-three patients (58%) had
      PPH. By 15 minutes norepinephrine had significantly increased in PPH-negative
      subjects while it rose more slowly in PPH-positive patients and peaked by 45
      minutes after the meal. Norepinephrine levels in 15 minutes were lower in PPH
      positive than in PPH-negative ones (159.8 +/- 9.7 vs. 212.3 +/- 21.1 pg/ml, p =
      0.01). Epinephrine levels rose only in PPH-negative subjects and did not differ
      significantly at the different time points. However, the area under curve
      analysis showed significantly lower epinephrine values in PPH-positive subjects
      (2903 + 247 pg.min.ml-1 vs. 3710 + 284 pg.min.ml-1, p = 0.03). Dopamine increased
      in both groups, although it was lower in subjects with PPH during the entire
      study (15 minutes: 68.6 +/- 3.7 vs. 93.7 +/- 11.7 pg/ml, p = 0.02; 30 minutes:
      68.8 +/- 3.7 vs. 86.1 +/- 7.7 pg/ml, p = 0.03; 45 minutes: 60.5 +/- 4.2 vs. 79.7
      +/- 5.2 pg/ml, p = 0.006). The postprandial C-peptide response did not differ
      between patients with PPH and those without PPH. CONCLUSIONS: In patients with
      essential hypertension, a marked decline in postprandial systolic blood pressure
      is associated with lower postprandial levels of norepinephrine, epinephrine and
      dopamine as compared to subjects without postprandial hypotension. This indicates
      that impaired sympatho-adrenal activation after ingestion of a meal may
      contribute to the development of PPH. Insulin appears not to be involved in the
      pathogenesis of postprandial hypotension.

PMID- 11467089
TI  - Importance of surveillance of tularemia natural foci in the known endemic area of
      Central Europe, 1991-1997.
AB  - INTRODUCTION AND PURPOSE: Marked activation of natural foci of tularemia in the
      known endemic area of Central Europe, comprising the borderland of Slovakia,
      Austria and the Czech Republic, led to an epidemic outbreak in western Slovakia
      and an increase in the number of human tularemia cases in the adjoining regions
      of northeastern Austria and southern Moravia from 1995 to 1997. The aim of this
      paper was to present the results of a longitudinal study on the prevalence of
      infection with Francisella tularensis in small mammals and ticks in six
      localities of western Slovakia and northeastern Austria from 1991 to 1997, and to
      draw attention to the importance of systematic surveillance of natural foci for
      epidemiologic prognoses and for taking preventive measures. METHODS: In Slovakia,
      three localities of the Zahorie lowland were monitored for 3 to 6 years (1991 to
      1996) for the presence of F. tularensis in small terrestrial mammals. In Austria,
      small mammals and ticks from three localities were investigated for 1 to 3 years
      (1994 to 1997). Spleens of live-trapped animals (at 1- to 2-month intervals) and
      ticks collected by flagging (in 6- to 8-week intervals) were examined by
      inoculation of pools into white mice, or individually by cultivation. RESULTS: In
      four localities under investigation (three localities in western Slovakia and one
      in Austria), a nearly simultaneous flare-up of tularemia epizootics was recorded
      in the autumn of 1994. The highest mean prevalence of infection in small mammals
      was 3.9% in the last quarter of the year, which along with isolations of F.
      tularensis from Dermacentor reticulatus ticks collected from vegetation in the
      locality of Austria (1.3% positivity), indicated the high epizootic activity of
      foci. F. tularensis was isolated from five rodent species--Apodemus flavicollis,
      A. sylvaticus, Clethrionomys glareolus, Microtus arvalis and Sorex araneus. From
      1995 to 1996, the persistent activity of the focus was repeatedly confirmed by
      isolations of F. tularensis from D. reticulatus ticks. In 1995 a natural focus of
      tularemia was detected in a further locality of Austria, where the agent was
      isolated from D. reticulatus. The increased epizootic activity of foci in the
      endemic region of Central Europe indicated a higher risk of acquiring tularemia
      for humans and was, in fact, followed by an epidemic outbreak in western Slovakia
      as well as by a large number of cases in Austria and the Czech Republic.
      CONCLUSION: Our findings clearly demonstrate that long-term surveillance of
      natural foci in endemic regions provides useful information on the activation of
      tularemia foci before the onset of epidemic outbreaks, thus permitting timely
      epidemiologic prognoses and the institution of preventive measures.

PMID- 11467090
TI  - Diltiazem versus nitroglycerin for myocardial protection following coronary
      artery bypass grafting as assessed by dobutamine stress echocardiography.
AB  - BACKGROUND: Perioperative infusion of the calcium channel antagonist diltiazem
      reduces the occurrence and extent of postoperative myocardial ischemia. However,
      recent reports also mention nitroglycerin as the drug of choice to prevent
      conduit spasm after coronary bypass grafting. The diagnosis of myocardial
      ischemia in the perioperative setting is still problematic. Dobutamine stress
      echocardiography (DSE) is an established technique that combines inotropic
      stimulation with real-time myocardial imaging and delineates normal and abnormal
      regional contraction patterns. We assessed the perioperative anti-ischemic
      effects of diltiazem and nitroglycerin during hemodynamic stress using DSE.
      METHODS: 50 adult patients were included in a prospective randomized study.
      Diltiazem or nitroglycerin was used from the onset of extracorporeal circulation
      until 24 h postoperatively. Dobutamine stress echocardiography was performed in a
      stepwise fashion 2 to 3 h after elective coronary artery bypass grafting.
      RESULTS: In 42 of 49 patients, dobutamine stress echocardiography either reached
      a level of 40 micrograms/kg/min dobutamine or achieved the target heart rate. One
      patient improved in terms of segmental wall motion abnormalities and three
      patients developed new abnormalities without corresponding electrocardiographic
      changes. Analysis of ischemia-sensitive parameters showed lower creatine kinase
      MB (p = 0.032) and troponin I levels (p = 0.1) in the diltiazem group 24 h
      postoperatively. Heart rate was significantly lower in the diltiazem group (p =
      0.0003). CONCLUSIONS: Under conditions of hemodynamic stress, DSE revealed no
      significant difference between diltiazem and nitroglycerin with regard to renewed
      ischemia.

PMID- 11467091
TI  - [Results of molecular diagnosis in 30 Austrian families with familial adenomatous
      polyposis].
AB  - Familial adenomatous polyposis is a dominantly inherited precancerous condition
      of the colorectum. The isolation of the responsible gene has facilitated the
      search for mutation in affected individuals and risk estimation for family
      members. The aim of our study was the assessment of the disease by molecular
      biological methods in order to estimate the risk for family members. Blood probes
      from 30 non-related Austrian families (44 persons affected, 61 at risk) were
      examined for detection of a defect in the adenomatous polyposis gene by means of
      the protein truncation test and, if necessary, by linkage analysis. The protein
      truncation test led to successful identification of the defect gene in 66.7%
      (20/30 families). In 3 families, the presymptomatic difference between mutation
      carriers and healthy subjects could only be assessed by linkage analysis. Genetic
      diagnosis enabled us to detect the disease before the onset of clinical symptoms
      in 16 persons at risk, 37 could be identified as genetically healthy. In 8
      persons at risk out of 5/30 families we were unable to identify a defect gene by
      the methods used until now. In conclusion, we have succeeded in establishing
      genetic diagnosis of familial adenomatous polyposis using the protein truncation
      test in Austria. Our method of genetic risk estimation is an important step in
      Austria towards earlier diagnosis and well-timed therapy management, and helps to
      exclude persons at risk who are genetically healthy from the laborious screening
      program.

PMID- 11467092
TI  - [Non-closure of peritoneum at cesarean section. Results from repeat cesarean
      sections].
AB  - OBJECTIVES: A number of publications advocate the short-term advantages of
      peritoneal nonclosure at cesarean section. However, currently there are no hard
      data available about long-term results and the repeat cesareans. MATERIAL AND
      METHODS: The study group of this retrospective analysis consisted of 30 women who
      underwent a repeat cesarean delivery, after a previous cesarean without closure
      of the visceral and parietal peritoneum. The control group (n = 31) had undergone
      peritoneal closure at the primary operation. All cesareans were performed at the
      same institution between 04/01/1997 and 12/31/1998 (first operation), and
      01/01/1999 and 06/30/2000 (repeat operation). RESULTS: The mean operation time
      was 38.9 (+/- 11.6) minutes in the study group and 44.2 (+/- 13.6) minutes in
      controls (p = 0.05). The mean incision-delivery time was 6.7 (+/- 3.2) minutes in
      the study group and 9.1 (+/- 3.9) minutes in controls (p < 0.01). No difference
      in intraoperative blood loss was observed between the two groups. In each cohort
      one case with significant intraabdominal adhesions was observed. CONCLUSION: Our
      results indicate that nonclosure of the peritoneum at primary cesarean section
      does not promote intraabdominal adhesions. This appears to be beneficial for the
      repeat cesareans.

PMID- 11467093
TI  - First documented case of infection with the tick-borne encephalitis virus in
      Vorarlberg, Austria.
AB  - The present study provides evidence and documentation of the first case of
      infection with the tick-borne encephalitis (TBE) virus acquired in the federal
      state of Vorarlberg (Austria). The area in which the viral infection was
      discovered lies in the vicinity of Ludesch in the Illvalley (Bludenz district).
      In order to investigate the current state of immunity to TBE in the Vorarlberg
      community, a total of 218 representative sera samples taken from donors resident
      in the districts of this state were investigated for antibody titers (IgG) of
      TBE. 38% of the samples had antibody titers representative of sufficient patient
      immunity, with the highest immunity (63%) in persons aged 20-40 years. Donors
      living in urban areas had a higher percentage of immunity (43%) than those living
      in rural areas (33%). Further, men were more immune to infection (43%) than women
      (33%). The lowest level of immunity (18%) to TBE was found in the Bregenzerwald
      communities. Based on this report, wider criteria for administering TBE vaccines
      to patients from the Illvalley should be applied, in particular among the elderly
      and those living in rural areas.

PMID- 11467094
TI  - Performance improvement in hospice care.

PMID- 11467095
TI  - The fear of death and the physician's responsibility to care for the dying.

PMID- 11467096
TI  - Medical marijuana.

PMID- 11467097
TI  - Process evaluation of an educational intervention to improve end-of-life care:
      the Education for Physicians on End-of-Life Care (EPEC) program.
AB  - Despite the growing importance of end-of-life care and the need to improve it,
      physicians receive little formal training in palliative care. The Education for
      Physicians on End-of-life Care (EPEC) project, developed by the American Medical
      Association and the Robert Wood Johnson Foundation, tested a train-the-trainer
      educational intervention to address this deficiency. This paper presents data
      from a process evaluation of the initial rollout of EPEC. By all accounts, EPEC
      provided a state-of-the-art curriculum covering important and clinically relevant
      topics to the care of the dying patient. It was less clear, however, if EPEC
      adequately prepared trainees to teach these new skills to other practicing
      physicians. Factors that may advance efforts to generalize EPEC to other settings
      and improve future applications of the program are discussed.

PMID- 11467098
TI  - The Harry R. Horvitz Center for Palliative Medicine (1987-1999): development of a
      novel comprehensive integrated program.
AB  - The Cleveland Clinic is a large multispecialty group practice. The need for a
      palliative care program was identified and the program started in 1987. A key
      concept has been that the existing structure of hospice care as defined by
      Medicare is insufficient to address the needs of patients with incurable disease.
      The field of palliative medicine implies physician expertise in several key
      areas: (1) communication; (2) decision-making; (3) management of complications;
      (4) symptom control; (5) care of the dying; and (6) psychosocial care. The
      development of the program (the first in the United States) since 1987 has put in
      place the following major services, listed consecutively: (1) hospital
      consultation service; (2) outpatient clinics; (3) acute care inpatient service;
      (4) hospice and home care service; (5) acute-care palliative medicine inpatient
      unit; and (6) hospice inpatient facility. Program development has meant that a
      new program has been introduced approximately every 18 months since the start of
      the program. This has considerable implications for staffing, the management of
      change, and competition for scarce resources within a contracting health care
      budget. The staffing of the program has focused on developing specialized
      attending physicians using a multidisciplinary approach dedicated to enhancing
      the role of nursing in the field. The major budgeted areas are (1) the acute-care
      palliative medicine unit, and (2) the hospice and home care service. Specific
      commitment has been made to research and education because of the desire to
      develop an intellectual basis for the practice of palliative medicine. This
      requires structured activities in both areas with a systematic approach to
      research and education. The complexity of developing a service should not be
      underestimated. There has been consistent support for the program by senior
      leadership within the Cleveland Clinic Foundation, including the cancer center.
      The major lessons learned during program development have been: (1) to focus on
      quality of patient care; (2) to commit to academic endeavor in research and
      education; (3) to secure institutional commitment to program development; (4) to
      establish a positive, proactive, businesslike approach; (5) to defend budget and
      personnel, albeit within a difficult time in health care; and (6) to commit to
      success, i.e., never promise anything on which you do not deliver. The future
      development of post-acute-care services serving predominantly the chronically ill
      elderly population suggest an expanded administrative and conceptual role for the
      future development of palliative medicine to help serve the needs of the aging
      population in the United States.

PMID- 11467099
TI  - The terminally ill Muslim: death and dying from the Muslim perspective.
AB  - Islam holds life as sacred and belonging to God and that all creatures will die
      one day. Suicide is forbidden. Muslims believe death is only a transition between
      two different lives. The terminally ill Muslim desires to perform five ritual
      requirements. Do not resuscitate (DNR) orders are acceptable. A deceased Muslim
      must always be buried after being ritually washed and wrapped. There are
      different Muslim schools of thought, but they are united regarding their views on
      death and dying.

PMID- 11467100
TI  - Performance improvement in pain management for home care and hospice programs.
AB  - This performance improvement project was undertaken to determine staff competency
      in pain management in several home care and hospice programs. The process used
      involved identifying and establishing the project, diagnosing the cause,
      remedying the cause, and holding the gains. Once the problem was identified and
      confirmed, the group worked to improve the competency of staff.

PMID- 11467101
TI  - Marijuana in the management of amyotrophic lateral sclerosis.
AB  - Marijuana has been proposed as treatment for a widening spectrum of medical
      conditions. Marijuana is a substance with many properties that may be applicable
      to the management of amyotrophic lateral sclerosis (ALS). These include
      analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite
      stimulation, and sleep induction. In addition, marijuana has now been shown to
      have strong antioxidative and neuroprotective effects, which may prolong neuronal
      cell survival. In areas where it is legal to do so, marijuana should be
      considered in the pharmacological management of ALS. Further investigation into
      the usefulness of marijuana in this setting is warranted.

PMID- 11467102
TI  - Ibuprofen to rofecoxib: what does it all mean and what do I do now?
AB  - NSAIDs are used throughout the World Health Organization three-step analgesic
      ladder, and are indicated for pain in all stages of malignancy. Side-effects are
      common with NSAIDs. Much has been written about NSAIDs and COX, since the
      discovery of COX-1 and COX-2 isoforms. How do you choose the appropriate NSAID?
      The choice of NSAID continues to be dependent upon associated gastroduodenal
      toxicity and the related risk factors of individual patients. Choosing the
      appropriate NSAID should minimize the likelihood of needing additional
      medications to manage adverse effects and symptoms caused by the NSAID therapy
      itself.

PMID- 11467103
TI  - On the 10th anniversary of the organization of the American Academy of Hospice
      and Palliative Medicine (AAHPM): the first 10 years.
AB  - The American Academy of Hospice and Palliative Medicine (originally chartered as
      the Academy of Hospice Physicians in 1988) is an organization of physicians
      devoted to advancing hospice and palliative medicine in the United States. The
      academy's mission is "physicians dedicated to promoting quality hospice care for
      the terminally ill through medical education, research, and training." The
      academy obtained specialty recognition from the AMA in 1996 and became the first
      physicians' group to publish its position on physician-assisted suicide in 1991
      and again in 1997.

PMID- 11467104
TI  - And they flew.

PMID- 11467105
TI  - Portrait of Jake.

PMID- 11467106
TI  - Foreword: preventing medical accidents: is "systems analysis" the answer?

PMID- 11467107
TI  - Financial conflict of interest: an unresolved ethical frontier.

PMID- 11467108
TI  - System and responsibility: three readings of the IOM report on medical error.

PMID- 11467109
TI  - Medical error as false claim.

PMID- 11467110
TI  - Race, ethnicity and quality of care: inequalities and incentives.

PMID- 11467111
TI  - Toward a workable model of "no-fault" compensation for medical injury in the
      United States.

PMID- 11467112
TI  - Making clinical trials safer for human subjects.

PMID- 11467113
TI  - Ethical and legal issues in technology: xenotransplantation.

PMID- 11467114
TI  - How judicial myopia is jeopardizing the protection of people with HIV/AIDS under
      the ADA.

PMID- 11467115
TI  - A way out of the maze: federal agency preemption of state licensing and
      regulation of complementary and alternative medicine practitioners.

PMID- 11467116
TI  - Using grant funding for innovative projects.
AB  - As part of the Balanced Budget Act of 1997, Congress created the Medicare Rural
      Hospital Flexibility Program for limited-service hospitals. The program is
      intended to bolster fragile rural service through network development. As part of
      the program, states may create a program to convert hospitals to critical access
      hospital (CAH) status. CAH designation gives very small, rural hospitals staffing
      flexibility for providing emergency, outpatient, and short-stay inpatient
      services and Medicare reimbursement on a reasonable cost basis. Michigan now has
      14 critical access hospitals.

PMID- 11467117
TI  - Michigan hospitals build stronger families.
AB  - Each year in the United States, about one in three babies is born to an unwed
      mother. The United States Department of Health and Human Services is trying to
      stop the rise in illegitimate births with an attractive incentive offered to the
      five states that show the largest decrease in out-of-wedlock births. Michigan is
      a leader in the fight--winning the award both times it has been given out.

PMID- 11467118
TI  - New hospitals shaped by philosophy of care.
AB  - For most of the last century, hospitals were constructed around the needs of
      health care professionals. However, two new Michigan hospitals helped usher is a
      new era that moved the patient to the center of hospital design.

PMID- 11467119
TI  - A peach or a bad apple? Conducting background investigations. Conducting
      background investigations.
AB  - Sometimes reading resumes can be like translating a foreign language. The
      exaggeration and hyperbole can leave you flummoxed.

PMID- 11467120
TI  - New strategies for ER admissions.
AB  - Henry Ford Hospital, Detroit, operates a Level 1 emergency department. Last year,
      nearly 89,000 adults and children were treated; one-third were brought in with
      life-threatening conditions. This year, the emergency department expects to
      handle more than 100,000 patients. Patients with nonemergency problems sometimes
      wait four to six hours before being seen by a physician. Others get discouraged
      and leave.

PMID- 11467121
TI  - Creating a tapestry of diversity. Celebrate the cultural diversity of staff and
      patients.
AB  - A multifaceted program at the University of Chicago Hospitals (UCH) builds on the
      organization's diverse employee base and patient population. Called "Creating the
      Tapestry," the program focuses on cultural differences among employees and
      patients.

PMID- 11467122
TI  - What hospital trustees must do ... or find another line of volunteerism.
AB  - Being a hospital trustee today is hard work. In recent years, this "volunteer"
      role has become more demanding due to the environmental factors with which
      hospitals must contend: shrinking work force availability, reduced reimbursement
      (notably, the Balanced Budget Act), and troublesome physician relationships.

PMID- 11467123
TI  - The future of rural services.
AB  - About 20 percent of the US population lives in rural areas, but only 11 percent
      of physicians practice in rural communities. The number of primary care
      physicians per populations of 100,000 in rural areas range from one-third to two
      thirds of those found in urban areas. In addition, rural hospitals are facing
      significant operational and financial challenges.

PMID- 11467124
TI  - Holding medical records in the palm of your hand.
AB  - Imagine patients carrying their own medical records with them on a floppy disk.
      It's happening, and it's closer than you may think.

PMID- 11467125
TI  - Changing roles in the merger process.

PMID- 11467126
TI  - E-business, e-health, e-hospitals.
AB  - Many of the major forces of change impacting health care today have technological
      underpinnings, and many of the less desirable impacts may have technological
      solutions. Two related technological forces are transacting business, online (e
      business) and delivering health care online (e-health).

PMID- 11467127
TI  - Future on the fringes.
AB  - Set against the palm trees, riotous flowers, and golf courses of LaQuinta Resort
      and Spa in California is something new -- a destination health center. Minutes
      from seaweed wraps and hot stone massage is the option of comprehensive health
      evaluations (including 150 diagnostic tests and genetic testing), longevity
      medicine, sports medicine, health coaches, and an array of personal wellness and
      corporate health programs.

PMID- 11467128
TI  - Phase I of the Stark II final rule.
AB  - On Jan. 4, the Health Care Financing Administration (HCFA) issued final
      regulations implementing the Stark II ban on physician self-referral. These final
      regulations, which go into effect Jan. 4, 2002, are described as "Phase I" since
      they address only a portion of the Stark law. HCFA promises that additional final
      regulations implementing the remaining portions of the Stark II ban will be
      published at a future date. This article provides a brief overview of the
      highlights of the Phase I final regulations.

PMID- 11467129
TI  - No such thing as a bad day.
AB  - This is an excerpt from Hamilton Jordan's book No Such Thing as a Bad Day
      reprinted with permission.

PMID- 11467130
TI  - Hog wild.
AB  - In a little over a decade, Harley-Davidson went from being a symbol of everything
      that was wrong with American manufacturing to the archetypal American success
      story, a company that was able to beat the Japanese at their own game. Its
      secret: combining the best of Japanese business practices with closeness to the
      customer that is so intense it's scary.

PMID- 11467131
TI  - Are we having fun yet?
AB  - Are you stressed out? Is your in box taller than you are? Do you have suicide
      hotline on speed dial? If you're not having fun at work, you're not alone.

PMID- 11467132
TI  - Patient safety--the VA's experience.
AB  - An overarching principle of medicine is "First Do No Harm." Indeed, as the
      Institute of Medicine recently highlighted, without safety, there is no quality.
      The Veterans Health Administration of the Department of Veterans Affairs (VA),
      the nation's largest integrated health system, has made a commitment to safe
      patient care. Programmatic responsibility for supporting this commitment resides
      in the National Center for Patient Safety (NCPS).

PMID- 11467133
TI  - How to get and keep good workers.
AB  - In today's health care organizations, nothing is more critical than providing
      consistent service delivery on a daily basis. This can be accomplished through
      the work of dedicated individuals. The relationship to staff turnover and
      consistent service delivery has been well-documented and is crucial to the
      success of a health care organization.

PMID- 11467134
TI  - Caring and sharing: the 2001 Ludwig Award winners.
AB  - The ability to identify a community's needs and respond to those needs in a way
      that helps everyone is a key attribute of today's hospitals. A hospital is a
      community's primary center for health care education, resources and support. The
      2001 Ludwig Community Benefit Award winners are examples of what hospitals can do
      when they look beyond the hospital doors and help the communities that surround
      them. They partner with local individuals, schools, businesses and organizations
      to give back generously without asking for anything in return. They realize that
      caring for people in their community means creating a better place for everyone
      to live.

PMID- 11467135
TI  - Past goals/future challenges.
AB  - At the 2001 MHA Annual Corporate Membership Meeting in June, the Michigan
      Association of Hospital Auxiliaries (MAHA) saw one president step down and a new
      one begin a one-year appointment. The following are the thoughts of each woman as
      they assume their respective positions as counselor and president.

PMID- 11467136
TI  - Rural hospitals: innovate or capitulate.
AB  - Delivering health care in today's marketplace is a challenging proposition for
      most hospitals. Costs go up, but reimbursement doesn't. Rural hospitals face even
      more serious challenges than their urban counterparts. Fixed costs for
      pharmaceuticals and employees are about the same as those for hospitals in
      densely populated areas, but there are fewer patients with which to spread these
      costs, and rural reimbursement rates tend to be lower.

PMID- 11467137
TI  - Reliable mortality data: a powerful tool for public health.

PMID- 11467138
TI  - Tobacco Products Bill 2001: an aid to public health.

PMID- 11467139
TI  - Evaluation of the health and functional status of older Indians as a prelude to
      the development of a health programme.
AB  - BACKGROUND: An estimated 68 million Indians are above the age of 60 years;
      however, information on their health status and needs is limited. Experience in
      developed countries shows that multiple chronic illnesses, nutritional deficiency
      and functional disability are common features of old age. For the development of
      any health programme, reliable situational information is essential. We therefore
      assessed the health and functional status of older Indians seeking health
      services. METHODS: We carried out a prospective cross-sectional observational
      study on 1586 subjects > or = 60 years of age (1035 men and 551 women), who
      attended the Geriatric Clinic of the All India Institute of Medical Sciences, New
      Delhi. A clinical and laboratory evaluation was carried out through a pre
      designed protocol evolved after reviewing the relevant literature. The protocol
      included a questionnaire on demographic details, personal habits, socio-economic
      variables, family structure, past and present medical history, use of medications
      and aids, presence of certain common symptoms and perceived functional
      disability. Evaluation included a detailed physical examination, functional
      assessment, psychiatric assessment and a set of laboratory tests. RESULTS: Ninety
      five per cent of the subjects were < 80 years of age and 87% of them sought
      medical attention for an acute illness that had occurred in the month prior to
      their coming to our clinic. One or more chronic illnesses were present in 96% and
      each subject had a mean of 2.5 diagnoses. However, they suffered from a limited
      number of illnesses of which the 10 most common accounted for 80% of the
      diagnoses. Hypertension, cataract and osteoarthritis were the 3 most common
      illnesses. About one-third of a subset of 209 subjects had a psychiatric illness;
      depression accounted for 50% of all psychiatric illnesses. A detailed functional
      assessment was carried out in 1268 subjects which showed that deficits of vision
      and hearing were the most frequent disabilities. Impairment of daily activities
      and cognition accounted for 6.9% and 5.1% of the diagnoses, respectively. A
      majority of them considered their home free from the hazard of accidents and were
      sure of support from their families at times of need. CONCLUSION: Multiple
      chronic illnesses, frequent acute illnesses and deficits of vision and hearing
      are the major health and functional problems of the health-seeking older
      population in India. It is difficult to assess the total service needs of the
      population from this study because of its unrepresentative character, though it
      provides a fair picture of the expectations of care of older people in India.

PMID- 11467140
TI  - Risk factors of malaria in the fringes of an evergreen monsoon forest of
      Arunachal Pradesh.
AB  - BACKGROUND: The forested hilly and foothill regions of north-east India are
      highly endemic for malaria and have a distinct epidemiological pattern. Nearly
      half the reported cases of malaria are from these areas. A knowledge of the risk
      factors in this eco-geographic entity may be helpful in formulating a specific
      control strategy. Hence, we conducted a community-based epidemiological study in
      a hilly, forested terrain of Arunachal Pradesh and examined different socio
      demographic factors to identify those predisposing to the occurrence of malaria,
      especially Plasmodium falciparum infection, in such areas. METHODS: Four
      epidemiological surveys were carried out during 1997 in 7 villages located at the
      fringes of a forest (total population: 1177) under Nompong Primary Health Centre
      of Changlang district, Arunachal Pradesh. Blood slides were collected randomly
      from the inhabitants, irrespective of their fever status, ensuring at least 50%
      coverage. One hundred and thirty-four microscopically confirmed Plasmodium
      falciparum cases were identified and 536 controls were randomly selected from the
      list of uninfected inhabitants. Relevant socio-demographic information was
      obtained from both cases and controls. The data were analysed by simple and
      multiple logistic regression using the unconditional maximum likelihood method.
      RESULTS: Factors which were found to be strongly associated with Plasmodium
      falciparum malaria on univariate analysis were age, ethnicity, village of
      residence and accessibility to the nearest health care facility. However, in
      multiple regression analysis, after controlling for the effects of confounding
      variables, the only risk factor identified was accessibility to the nearest
      health care facility (adjusted odds ratio: 4.5; 95% CI: 1.8-11.3; p < 0.0001 for
      those at a distance of 2-8 km and adjusted odds ratio: 11.1; 95% CI: 4.1-30.0; p
      < 0.0001 for those > 8 km away). CONCLUSION: Distance, particularly non-motorable
      distance, from the place of residence to the nearest health care facility was a
      major risk factor for malaria in this hilly forested terrain. This indicates the
      need for special efforts to detect cases early and institute treatment promptly
      in such areas of the north-eastern region, so as to reduce the morbidity and
      mortality of malaria.

PMID- 11467141
TI  - Injection use in a village in north India.
AB  - BACKGROUND: Injections can transmit infections such as human immunodeficiency
      virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and precipitate
      poliomyelitis. Complications such as injection abscesses and nerve damage may
      also occur. It is estimated that 50% of the injections given in developing
      countries are unsafe. However, limited information is available from India. We
      planned a pilot study to assess the prevalence of injection use and the knowledge
      of the community and private medical practitioners (PMPs) about injection use.
      METHODS: One in every four houses in the village under study was selected by
      systematic random sampling. One adult (> 18 years) respondent in the family was
      asked questions about family members receiving injections in the past 6 months.
      Nine PMPs were interviewed about their knowledge and practices regarding
      injection use. RESULTS: In the past six months, 1280 family members in 285 houses
      received 1575 injections (2.46 injections per person per year). About 35% had
      received at least one injection in the past 6 months. Children below 5 years
      received 3.1 injections/child/year of which about 60% were preventive. On their
      last visit to a health facility, 55% of the subjects were given injections using
      disposable syringes. About 45% of the 285 respondents knew that diseases could be
      spread by improper use of injections. While 18% of the respondents said they
      would prefer injections, 54% preferred oral medications if both were equally
      effective. After being told the average cost of disposable needles and syringes,
      92% of the respondents were willing to buy them. None of the 9 PMPs practising in
      the village were formally trained in modern medicine. On the day of observation,
      18 of 58 patients (30%) seen by PMPs were given injections. Three injections were
      observed and though they were all given with disposable syringes, the technique
      of administration did not follow standard guidelines in any. Two PMPs did not
      know of any disease transmitted by injections. The syringes were usually thrown
      in a nearby drain or outside the village. Four PMPs said that patients themselves
      did not ask for injections. CONCLUSION: The use of injections in the study area
      was high. The PMPs were not only giving a high number of injections but the
      technique of administration was also wrong. The community was less likely to ask
      for injections on their own but was willing to buy disposable syringes and
      needles. The awareness about the risk of injections was low.

PMID- 11467142
TI  - Evaluation of two intradermal vaccination regimens using purified chick embryo
      cell vaccine for post-exposure prophylaxis of rabies.
AB  - BACKGROUND: Post-exposure prophylaxis for rabies with cell culture vaccines by
      the conventional intramuscular regimen is very expensive. The World Health
      Organization has advocated two cost-effective intradermal regimens with cell
      culture vaccines for use in developing countries. We evaluated these two regimens
      -the 2-site and the 8-site regimens--in terms of immunogenicity, safety and
      tolerance in people with category I exposure to rabies. METHOD: Eighty-two
      subjects who had mild category I exposure to rabies were immunized using a
      purified chick embryo cell vaccine. The first regimen given to 43 subjects,
      consisted of intradermal administration of 0.2 ml of vaccine at 2 sites on days
      0, 3 and 7 and at one site on days 28 and 90. The second regimen, given to 39
      subjects, consisted of intradermal administration of 0.1 ml of vaccine at 8 sites
      on day 0, at 4 sites on day 7 and at one site on days 28 and 90. The mouse
      neutralization test was used to estimate titres of rabies neutralizing antibody
      in these subjects on different days after vaccination. The subjects were followed
      up for 1 year. RESULTS: Both regimens produced adequate neutralizing antibody
      titres from day 14 onwards, though the second regimen produced a more rapid
      antibody response and significantly higher titres (p < 0.001) on all days tested.
      There were minimal side-effects and both regimens were well tolerated.
      CONCLUSION: Both the 2-site and 8-site intradermal regimens with purified chick
      embryo cell vaccine produce adequate levels of neutralizing antibodies but the 8
      site regimen appears to be more immunogenic. The feasibility of using these cost
      effective regimens in routine practice needs to be further evaluated under the
      field conditions prevalent in India.

PMID- 11467143
TI  - Integrated programme for control of geohelminths: a perspective.
AB  - Infestation by geohelminths is an important public health problem in developing
      countries like India. It is a major cause of morbidity in school-age children who
      have the highest burden of worm infestation. Some of the morbid conditions
      attributed to intestinal helminthiasis are malnutrition, growth retardation,
      anaemia, vitamin A deficiency and impaired intellectual performance. Chemotherapy
      targeted at school-age children has been recommended as a cost-effective and
      feasible control programme for the control of geohelminths. To optimize resources
      a geohelminth control programme can be integrated with other existing national
      health programmes. The availability of drugs such as diethyl carbamazine (DEC)
      and albendazole, which have anthelminthic and antifilarial properties, opens the
      possibility of integrating a geohelminth control programme with a filaria control
      programme. However, co-administration of DEC and albendazole raises several
      issues of frequency of administration, efficacy, compliance and cost
      effectiveness. Thus, integrating a geohelminth control programme with the
      existing mid-day meal or anaemia prophylaxis programme would be a more
      appropriate and cost-effective strategy to control geohelminths, alleviate the
      morbidity caused by them and improve the overall health of the community.

PMID- 11467144
TI  - Cause of death reporting systems in India: a performance analysis.
AB  - BACKGROUND: Reliable statistics on the causes of death in the population are
      essential for setting priorities in the health sector. Most cause of death
      reporting systems in developed countries rely on medical certification of the
      cause of death according to the International Classification of Death (ICD-10),
      and have achieved near-total coverage. Developing countries such as India, where
      adequate medical facilities are not available, depend on lay reporting of the
      cause of death in rural areas, using a sample registration system. The use of the
      cause of death statistics in India is questioned in view of the poor coverage,
      and poor compliance with guidelines for cause of death reporting, coding and
      classification. METHODS: A brief description of the reporting system in India is
      followed by the characteristics of a usable cause of death reporting system. We
      identified 9 criteria based on a review of the literature and our own assessment
      of the problem. The performance of the cause of death reporting system for rural
      and urban areas of India was examined against each of the 9 criteria. We offer a
      subjective rating on a three-category rating scale consisting of (i)
      satisfactory, (ii) tolerable, and (iii) poor. RESULTS: The major factors
      affecting the use of the cause of death statistics in India are: (i) poor
      coverage; (ii) high incidence of unclassifiable deaths; (iii) long delay and
      irregular publication of statistics; and (iv) lack of systematic screening.
      CONCLUSIONS: We recommend the following steps to improve the usability of cause
      of death statistics in India. Introducing periodical reviews jointly by the
      Departments of Health and Municipal Administration to identify non-reporting
      municipalities, sample units, and further identification of non-reporting health
      care institutions sustained over a period of, say, five years will raise coverage
      substantially. The other measures include: (i) training programmes to build up
      cause of death report writing skills among physicians; (ii) compilation and
      publication of cause of death statistics at the state level; (iii) sponsored
      research on the cause of death reporting structure and its implications for
      policy-making; and (iv) computerization of filling, tabulation and flow of cause
      of death statistics at the municipality and the state levels. To reduce the
      unusually high level of unclassifiable deaths, the Registration of Births and
      Deaths Act should be amended to ensure that hospitals and health care
      institutions maintain medical records. For accurate cause of death data from
      rural areas, we recommend that the performance of the sample registration survey
      cause of death (SRS-COD) component be evaluated according to the above criteria.

PMID- 11467145
TI  - Nucleic acids in disease prognosis.

PMID- 11467146
TI  - Public health situation 2000.

PMID- 11467148
TI  - When knowledge hurts....

PMID- 11467147
TI  - The eternal debate: Lakshmi versus Saraswathi.

PMID- 11467149
TI  - The newborn health agenda.

PMID- 11467151
TI  - A new anaesthetic regimen for excision of phaeochromocytomas.

PMID- 11467150
TI  - Tobacco and areca nut use in male medical students of Patna.

PMID- 11467153
TI  - Global tuberculosis control report.

PMID- 11467152
TI  - Resident doctors, bloodborne pathogens and universal precautions: are we sitting
      on a volcano?

PMID- 11467154
TI  - Mystery Siliguri fever solved?

PMID- 11467155
TI  - Neuroleptic use in the treatment of Post-Traumatic Stress Disorder.
AB  - BACKGROUND: There have been few studies of the use of neuroleptics in the
      treatment of Post-Traumatic Stress Disorder (PTSD). This study uses data from two
      large outcome studies to: (1) examine demographic and treatment characteristics
      associated with neuroleptic prescription in the treatment of PTSD, and (2)
      compare the outcomes of neuroleptic-treated patients with those not receiving
      neuroleptics. METHODS: A secondary analysis of an observational outcome study of
      831 inpatients and 554 outpatients (all males) receiving treatment at the VA for
      combat-related PTSD was performed. Patients were classified as having either
      received neuroleptics during the following year or not. Sociodemographic
      characteristics, treatment and medication history and detailed information about
      PTSD symptoms were obtained at baseline and 12 months. First, the two groups were
      compared with respect to the demographic and clinical variables. We then
      conducted a series of separate paired t-tests to determine whether there was
      significant improvement from baseline to follow up in each group and a series of
      analyses of covariance that compared outcomes in the two groups, adjusting for
      baseline differences. RESULTS: Approximately 9% of inpatients and 10% of
      outpatients were treated with neuroleptics. Patients who received neuroleptics
      had both more psychiatric and more social impairment. They also demonstrated more
      severe PTSD (especially intrusive symptoms) despite having similar combat
      exposure. Outcomes after one year for the group treated with neuroleptics were
      not significantly different from the group not treated with neuroleptics.
      CONCLUSIONS: Neuroleptic use in the treatment of PTSD is targeted at more
      seriously ill patients and was not associated with substantial improvement.

PMID- 11467156
TI  - The role of psychometric data in predicting inpatient mental health service
      utilization.
AB  - Inpatient mental health readmission rates have increased dramatically in recent
      years, with a subset of consumers referred to as revolving-door patients. In an
      effort to reduce the financial burden associated with these patients and increase
      treatment efficacy, researchers have begun to explore factors associated with
      increased service utilization. To date, predictors of increased service usage are
      remarkably discrepant across studies. Further exploration, therefore, is needed
      to better explicate the relevance of "traditional" predictors and also to
      identify alternate strategies that may assist in predicting rehospitalization.
      One method that may be helpful in identifying patients at high risk is the
      development of a psychometric screening procedure. As a means to this end, the
      present study was designed to assess the potential usefulness of psychometric
      data in predicting mental health service utilization. The sample consisted of 131
      patients hospitalized during an index period of 8 months at an acute-care
      psychiatric hospital. Number of readmissions was recorded in a 9 month post-index
      period. Measures completed during the index admission included the Brief
      Psychiatric Rating Scale-Anchored (BPRS-A), Symptom Checklist-90-Revised (SCL-90
      R), Kaufman Brief Intelligence Test (K-BIT), and the Beck Depression Inventory
      (BDI). Results indicated that psychometric data accounted for significant
      variance in predicting past, present and future mental health service
      utilization. The BPRS-A, SCL-90-R, and BDI show particular promise as time
      efficient psychometric screening instruments that may better enable practitioners
      to identify patients proactively who are at increased risk for rehospitalization.
      Implications are discussed with regard to patient-treatment matching and
      discharge planning.

PMID- 11467157
TI  - Characteristics of staff victims of patient assault: ten year analysis of the
      Assaulted Staff Action Program (ASAP).
AB  - Patient assaults on staff have been a continuing risk for inpatient and community
      based psychiatric healthcare providers. This study presents a ten-year analysis
      of the characteristics of staff victims of patient assaults in one public mental
      health system of care, a period which included the transition to managed care
      initiatives within this system. Assault data was gathered within the context of
      the Assaulted Staff Action Program (ASAP), a voluntary, system-wide, peer-help,
      crisis intervention program that is designed to assist employees with the
      psychological sequelae of these patient events. In general, the findings were
      consistent with previously reported inpatient and community studies. Less
      experienced, less formally trained employees remain at high risk. The impact of
      managed care initiatives was found in community residences where younger female
      staff were most at risk. The implications of the findings and possible risk
      management strategies are discussed.

PMID- 11467158
TI  - Further defining anxiety and depressive disorders. Introduction.

PMID- 11467159
TI  - Defense styles and Personality dimensions of research subjects with anxiety and
      depressive disorders.
AB  - We used the Bond Defense Style and Cloninger Tridimensional Personality
      questionnaires to assess defense styles and personality dimensions in subjects
      with anxiety and depressive disorders. When measured against a comparison group,
      maladaptive defense style scores were significantly higher in those with major
      depression, panic disorder, generalized anxiety disorder, and social phobia, and
      higher at a trend level in the subjects with obsessive-compulsive disorder and
      mixed anxiety and depression. However, there were no differences in adaptive
      defense style scores between the subjects and the comparison group. The harm
      avoidance personality dimension scores were significantly higher in subjects with
      both anxiety and depressive disorders than in the comparison group. The harm
      avoidance scores correlated positively with the maladaptive defense scores, but
      negatively with the adaptive defense scores. These findings are discussed in
      terms of severity of illness, level of functioning, and relationships between
      Axis I and II disorders.

PMID- 11467160
TI  - Assessment of state and trait anxiety in subjects with anxiety and depressive
      disorders.
AB  - The State-Trait Anxiety Inventory (STAI) is one of the most widely used scales
      for the evaluation of anxiety in medical and, to a lesser extent, psychiatric
      patients. Although there is a relatively large amount of STAI data about anxiety
      for individuals with a variety of psychiatric disorders, the results of many
      anxiety studies include only state or trait and many studies have been influenced
      by comorbidity and by variations in diagnostic criteria used. We studied state
      and trait anxiety and compared the revised form of the STAI (Form Y) with the
      original (Form X) to evaluate the anticipated improvement in the measure. In
      addition, we compared the STAI results with those of another self-report measure
      (the Symptom Checklist-90 anxiety and depression scales) and also with
      interviewer-rated measures of anxiety (Hamilton Rating Scale for Anxiety) and
      depression (Hamilton Rating Scale for Depression). Results indicate that the STAI
      does not clearly differentiate anxiety disorders from depressive disorders and
      support the use of multiple tests and of both self-report and interviewer ratings
      in the evaluation of anxiety and depression in psychiatric patients.

PMID- 11467161
TI  - The ability of the Symptom Checklist SCL-90 to differentiate various anxiety and
      depressive disorders.
AB  - We studied the use of the Symptom Checklist-90 (SCL-90) to differentiate between
      specific anxiety and depressive disorders and/or their symptoms in 280 patients
      with 6 DSM-III-R diagnoses: major depression (MD), panic disorder (PD),
      generalized anxiety disorder (GAD), social phobia (SP), obsessive-compulsive
      disorder (OCD), and mixed anxiety and depression (MAD). Using a comparison group,
      we found specific patterns for some of the diagnostic categories. Both the MD and
      MAD subjects had significantly high paranoid ideation, interpersonal sensitivity,
      hostility, and psychoticism, as well as high depression subscale scores; those
      with PD and GAD has the highest anxiety and somatization scores; and those with
      SP or OCD had a mixed pattern. When ranking the severity of psychopathology, the
      disorders ordered from most to least were MAD, MD, PD, GAD, SP, and OCD.
      Subsyndromal levels of symptoms frequently were associated with the various
      conditions. Use of the SCL-90 subscale helps to enlarge our understanding of the
      various anxiety and depressive disorders.

PMID- 11467162
TI  - New devices, techniques could mean changes in bypass surgery.

PMID- 11467163
TI  - How successful operating rooms build in a culture of teamwork.

PMID- 11467164
TI  - Artery bypass done without surgery.

PMID- 11467165
TI  - Ladders have rungs for surgical techs.

PMID- 11467166
TI  - Charge nurses juggle many needs.

PMID- 11467167
TI  - CJD: how to process instruments.

PMID- 11467168
TI  - Scorecard helps steer surgery center.

PMID- 11467169
TI  - Top strategies to attract and keep RNs.

PMID- 11467170
TI  - Nurses rally to ban forced overtime.

PMID- 11467171
TI  - The ubiquitous lipids and related diseases: a laboratory perspective.

PMID- 11467172
TI  - Laboratory automation: a case study.

PMID- 11467173
TI  - News from the latest CLIAC meeting.

PMID- 11467174
TI  - Using chi-square and a PC to assess competency.

PMID- 11467175
TI  - New bill would address legislative priorities for labs; Congress agrees to help
      the uninsured.

PMID- 11467176
TI  - Outbreaks of Escherichia coli O157:H7 infections among children associated with
      farm visits--Pennsylvania and Washington, 2000.

PMID- 11467177
TI  - Sudden death in a traveller following halofantrine administration--Togo, 2000.

PMID- 11467178
TI  - BARF: "bones and raw foods" or "biologically appropriate raw foods"--fad, fiction
      or fanatical?

PMID- 11467179
TI  - An ethicist's commentary on the case of conflict between husband and wife over
      treatment of a pet.

PMID- 11467180
TI  - Questions associated with proposed changes to the criminal code.

PMID- 11467181
TI  - Large animal practitioners in Ontario deserve better support from their
      veterinary association(s).

PMID- 11467182
TI  - A study in animal ethics in New Brunswick.
AB  - Society uses animals in ever-increasing numbers and ways, providing ethical
      challenges. Decisions about animal use are guided by the social consensus ethic
      towards animals. Because there is no clear social consensus ethic, these
      decisions are difficult. Society's ethic is changing and a "new ethic" towards
      animals is emerging. This study addressed the need to better understand society's
      ethics towards animals. Qualitative research methodology (focus groups) was used
      to study 7 different animal-interest groups. Qualitative data analysis was
      computer-aided. The group ethical position towards animals of its own group
      interest was determined for each group. The animal welfare, companion animal, and
      veterinary groups took Rollin's Position, a position based on both the
      Utilitarian and the Rights Principles; the farmer and trapper groups the
      Utilitarian/Land Ethic position, a dual position based on actions producing the
      greatest amount of pleasure and the least amount of pain for the greatest number,
      and preserving the integrity, stability, and beauty of the biotic community; the
      hunter group the Utilitarian/Judeo-Christian position, a dual position based on
      actions producing the greatest amount of pleasure and the least amount of pain
      for the greatest number, and having dominion over animals; and the naturalist
      group took Rollin's Position/Land Ethic. All these groups perceived medium to
      extreme ethical responsibility towards animals of their own group's interest that
      are used by others. The study showed that the predicted "new ethic" towards
      animals is in New Brunswick society and it is Rollin's Position.

PMID- 11467183
TI  - Association of porcine circovirus 2 with reproductive failure in pigs: a
      retrospective study, 1995-1998.
AB  - In order to determine if vertically transmitted porcine circovirus (PCV) has
      played a role in reproductive failure in pigs in areas of endemic infection,
      archival fixed tissues were examined by polymerase chain reaction (PCR) and
      immunohistochemistry. Tissues tested were from routine cases of abortion or
      reproductive failure submitted between 1995 and 1998 to the diagnostic laboratory
      at the Western College of Veterinary Medicine, Saskatoon. They originated from 29
      high-health herds in the provinces of Alberta and Saskatchewan and comprised a
      total of 36 individual submissions. Porcine circovirus type 1 (PCV1) was not
      detected by PCR in any submitted tissues. Porcine circovirus type 2 (PCV2) was
      not detected by PCR or immunohistochemistry in any of the submitted tissue. The
      effect of extended formalin fixation on the detection of PCV2 by PCR was assessed
      and fixation for up to one week had no gross effect on sensitivity of detection
      using this PCR technique. Failure to detect porcine circoviruses in cases of
      reproductive failure prior to 1999 in areas of endemic infections, suggests that
      reproductive disease may be a new clinical manifestation of PCV2 infection, and
      that vertical transmission may not have been the primary mechanism of initial
      dissemination of the virus in the pig population.

PMID- 11467184
TI  - Multiple porcine circovirus 2-associated abortions and reproductive failure in a
      multisite swine production unit.
AB  - Porcine circovirus type 2 was detected in several stillborn and nonviable
      neonatal piglets presenting with chronic passive congestion, cardiac hypertrophy,
      and severe diffuse myocarditis. The presence of the virus in the heart and other
      tissues of affected piglets was confirmed by polymerase chain reaction,
      immunohistochemistry, and virus isolation techniques. Other reproductive losses
      and associated infectious agents in the herd are discussed.

PMID- 11467185
TI  - Suspect copper toxicity in an alpaca.
AB  - An alpaca presented in lateral recumbency and subsequently died. On necropsy
      examination the liver showed severe, widespread, periacinar hepatocellular
      necrosis, staining positive to a rhodamine stain for copper. Hepatic copper
      concentration was elevated. Copper toxicity in the camelid is difficult to
      diagnose, since the classical hemolytic crisis is not observed.

PMID- 11467186
TI  - Repair of collateral ligament instability in 2 foals by using suture anchors.
AB  - Instability of the collateral ligaments of the carpal or metacarpophalangeal
      joint occurred in 2 foals. The instability was repaired using commercial suture
      anchors. In foals, commercial suture anchors combined with external coaptation
      can be used successfully to repair collateral ligament instability of the carpus
      or the metacarpophalangeal joint.

PMID- 11467187
TI  - Organophosphate poisoning in a group of replacement heifers and dry cows.
AB  - Terbufos ingestion caused acute organophosphate poisoning in 67 Holstein heifers
      and dry cows, 7 months to 5 years old. Overall mortality was 31%, with attack
      rates of 4% and 48% for the dry cows and heifers, respectively. Less severely
      affected animals were treated with atropine sulfate for 7 days.

PMID- 11467188
TI  - Traumatic diaphragmatic hernia in a clinically normal dog.
AB  - A 3.5-year-old border collie was presented for routine ovariohysterectomy. A
      preoperative physical examination revealed no abnormalities, but, under
      anesthesia, the patient became dyspneic and cyanotic. Plain radiography indicated
      the presence of a diaphragmatic hernia. The herniated structures were returned to
      the abdomen and the diaphragmatic defect was surgically repaired.

PMID- 11467189
TI  - Diagnostic ophthalmology. Bilateral idiopathic uveitis in a llama.

PMID- 11467190
TI  - Your CEO. Are you short-staffed or short-sighted?
AB  - Hiring the right CEO is the board's most important job. You may want to look
      outside of the usual hierarchy for your next chief exec--but be sure you know
      what you want. And don't leave succession planning until you are left leaderless.

PMID- 11467191
TI  - Good fortune. Griffin Hospital gets outstanding grades in both employee and
      patient satisfaction.
AB  - While the rest of the country suffers a workforce crisis, a Connecticut hospital
      is turning away applicants. After adopting the Planetree model of care, Griffin
      Hospital's patient and employee satisfaction rates soared.

PMID- 11467192
TI  - Striking a balance.

PMID- 11467193
TI  - Bridging the workforce shortage.
AB  - Some hospitals and systems have devised innovative ways to fill employee
      vacancies: they are providing educational opportunities for employees to learn
      new skills, which makes use of their hospital experience and engenders their
      loyalty.

PMID- 11467194
TI  - Cleveland Clinic television series enhances branding in active market.
AB  - "Medical Miracles" premiered April 26. It is an information-packed series of
      programs showcasing The Cleveland Clinic's advanced medical practices. The
      Cleveland Clinic teamed with local NBC-affiliate, WKYC to develop half-hour shows
      on topics including neuro-sciences, orthopedics, eye, heart, pediatrics and
      cancer. As of this writing, three of the half-hour shows already have aired. They
      will resume in September, October and November, following a summer break. The
      collaboration is a healthy prospect all the way around. For Cleveland Clinic, it
      provides highly credible  visibility in a    competitive marketplace. And,
      according  to WKYC president and general manager, Brooke Spectorsky, " Medical
      news and information is a high priority among our viewers."

PMID- 11467195
TI  - In Seattle, Children's Hospital makes kids more aware of safety. Hospital scores
      big with Seattle Mariners, Safeco Insurance.
AB  - To leverage existing relationships, Children's Hospital (Seattle), the Seattle
      Mariners baseball team and Safeco Insurance teamed up to educate parents and
      children about home safety and emergency preparedness. The resulting multi media
      Safety All Stars program used a colorful, widely distributed safety poster to
      stimulate participation, and special activities knocked the message "home."

PMID- 11467196
TI  - Louisiana hospital's wellness center popular for health maintenance. East
      Jefferson General focuses on those 50 and over.
AB  - East Jefferson General Hospital in Metairie, La., conducted comprehensive
      research prior to developing its new Wellness Center. Newspaper, direct mail and
      internal publications advertising boosted interest, as did employees wearing "Ask
      Me About The Wellness Center" buttons. Through satellite sales offices in the
      hospital and at a local shopping mall, more than 900 people purchased memberships
      before the center opened, and now an average of 600 to 700 people visit the
      center daily.

PMID- 11467197
TI  - Delnor-Community marketing shows hospital's human side.
AB  - Delnor-Community Hospital, Geneva, Ill., used cable TV, outdoor boards and
      regional newspapers to introduce a new logo and themeline. The logo is usually
      described as "two ascending wings," and it conveys a lot of messages. Advertising
      features physicians and their compassionate, human approach.

PMID- 11467198
TI  - Hillcrest Hospital campaigns in competitive Cleveland. Focus is on
      cardiovascular, cancer and pediatrics.
AB  - In suburban Mayfield Heights, Ohio, Hillcrest Hospital faced down competition by
      focusing advertising on three areas: cardiology, pediatric care and cancer
      treatment. It adopted the tagline, "Close to home" and used direct mail to inform
      the community about its facilities and invite residents to a series of open
      houses. Print ads, TV and billboards continued to reinforce the theme.

PMID- 11467199
TI  - Web site for St. Jude Children's is lively with media, volunteer info. 'Danny
      Thomas' hospital' helps children with research.
AB  - The Web site for St. Jude Children's Research Hospital, Memphis, Tenn., is lively
      with volunteer and fundraising information. The importance of media coverage is
      recognized in a section which provides a generous selection of radio, TV and
      print material.

PMID- 11467200
TI  - MountainStar Healthcare makes a unique appeal to healthcare brokers. Improves
      recognition in a competitive market.
AB  - MountainStar Healthcare, the Utah segment of HCA (The Healthcare Company),
      partnered with the health plans that shared a common interest: all were in
      competition with multi-state Intermountain Health Care. Mountain Star promoted
      its outstanding record of service--to healthcare brokers! An information kit,
      including a "Quality Report Card" and cost analysis proved to be an effective
      tool.

PMID- 11467201
TI  - An overview of biochemical markers in acute coronary syndromes.
AB  - The cardiac troponins (cTns), cTnT and cTnI, are currently regarded as being the
      most useful diagnostic and prognostic biochemical markers of myocardial damage in
      patients with suspected acute coronary syndromes (ACSs). In spite of the evidence
      based nature of this observation, the uptake of serum cTn measurement in routine
      clinical practice--in both the UK and elsewhere, is patchy, indeed, there still
      exists wide variability in the range of testing and sampling strategies involving
      usage of the many existing cardiac markers. For evaluating suspected acute
      myocardial infarction (AMI) and other ACSs, international opinion favours either
      serum cTnT or cTnI (measured 12-24 h after admission to the emergency room)-
      together with a short-time window marker such as serum creatine kinase (CK)
      (measured on admission and perhaps again within the 12-24 h window). Translation
      of this strategy into universal clinical practice would require not only
      formulation of, but also strict adherence to, agreed clinical decision-making
      protocols which, in turn, would need to be backed by adequate funding.

PMID- 11467202
TI  - Risk reduction for DDT toxicity and carcinogenesis through dietary modification.
AB  - Organochlorine pesticides, including dichlorodiphenyltrichloroethane (DDT), are
      an environmental hazard due to their persistent nature and potential health
      effects. DDT and 1,1,dichloro-2,2,bis(p-chlorophenyl)ethylene (DDE) are lipid
      soluble pesticides which accumulate in fatty tissues and are, therefore, more
      present in fat-containing foods such as meat, fish, milk, cheese and oil than in
      fruit, vegetables and grain. Scientists have for some time been concerned about
      the human exposure to DDT and the potential risk of breast cancer due to its
      oestrogenic activity. The introduction of foods containing chemopreventive agents
      in the diet could inhibit the oestrogenic effects of DDT and the risk of
      developing cancer. Phytooestrogens are weak oestrogens found in certain plants
      such as soybean. They compete with DDT for oestrogen receptors and inhibit the
      oestrogenic effect of DDT on cultured human breast (MCF) cells. Curcumin, a spice
      widely used in Indian dishes, has anti-carcinogenic and anti-inflammatory
      properties. It also inhibits the oestrogenic effects of DDT and is synergistic
      with phytooestrogens. Indole-3-carbinol, a compound naturally found in
      cruciferous vegetables, stimulates oestrogen metabolism towards 2-hydroxyoestrone
      which reduces the oestrogenic response in MCF cells and the risk of breast
      cancer. Since DDT is lipid soluble and accumulates in adipose tissue it could
      have a role in lipid metabolism. Would a low fat diet reduce DDT bioaccumulation?
      A reduction in calories can decrease oestrogen levels and possibly reduce the
      risk of breast cancer. A dietary modification with the introduction of soy
      products, curcumin, cruciferous vegetables and low fat could be beneficial in
      reducing the risk of developing cancer and possibly the effects of DDT.

PMID- 11467203
TI  - Risk factors for infant mortality in a rural community in Nigeria.
AB  - In this prospective community based study, information on births and deaths was
      collected for five consecutive years (1993-1997) by trained village health
      workers (VHW) and traditional birth attendants (TBA). The main objective was to
      identify factors which are associated with infant deaths in a typical rural
      community in southwestern Nigeria with a current mid-year population of 3,308.
      Infant mortality rate was found to be 68.2 per 1,000 live births and is lower
      than the national rate but higher than the regional rate. Neonatal deaths, with a
      rate of 37.6 per 1,000 live births, accounted for 55.1% of all infant deaths
      while postneonatal deaths accounted for 44.9% of the deaths. Twelve (44.4%) of
      all neonatal deaths (27) occurred within 24 h of delivery while 20 (74.1%) of all
      neonatal deaths occurred in the first week of life and were perinatal deaths.
      These high perinatal rates indicate that more efficient obstetric and public
      health services are needed in the community. First birth order and older mothers
      (> 34 years) at time of death of infant were associated with significantly higher
      risk for mortality in this village (p = 0.004). Females were twice as likely as
      males to die in infancy (p = 0.011), a finding which is contrary to what is
      generally found; there is a need for further studies to exclude gender
      discrimination in this village. Significantly more neonatal deaths occurred
      during the rainy season than in the dry season (p = 0.018) suggesting that
      environmental factors play a role in neonatal deaths. In the neonatal period, the
      commonest cause of death was due to complications of low birth weight while in
      the postneonatal period it was due to infection. VHWs and TBAs are good resource
      persons for obtaining accurate numerical data at the grass-roots level, and the
      potential of using their services to collect vital but non-existent statistics
      should be explored. These workers also need to be trained to recognise factors
      that put infants at risk. Reassessment of preventive strategies already
      implemented for reducing infant mortality may be required in order to further
      reduce the infant mortality rate in this community.

PMID- 11467204
TI  - The role of traditional birth attendants in Atakumosa, Nigeria.
AB  - All 26 traditional birth attendants (TBAs) and their 109 clients in 15
      settlements in Atakumosa West Local Government Area (LGA) in Nigeria were
      interviewed to assess TBA training, practices and utilisation. The study showed
      that more than 80% of TBAs were older women with more than four children,
      practiced single-handedly and held other occupations. About 54% of those studied
      had no designated room for deliveries; twenty-one (80.8%) did not consider any
      pregnant woman to be at high risk; three (11.5%) perform intravaginal
      examinations during labour and only a few recognise complications; twelve (46.2%)
      never refer patients. Despite these deficiencies, TBAs continue to practise in
      appreciable numbers and their services continue to be on demand in the
      communities under study. Nearly all of the clients interviewed had started to use
      TBAs by the age of 25 and 50% had used TBAs for all of their deliveries. Most
      TBAs provide antenatal care and 77% had a case load of less than five clients per
      month. Ninety-six per cent of the clients had not been referred by the TBA
      before. Although 61% of clients felt TBAs in a future pregnancy and 49% would
      recommend TBA care to other women. Low socio-economic status, illiteracy, poor
      awareness of modern maternal health (MCH) facilities, personalized care, strong
      family influence and easy access to TBA services were strong factors promoting
      traditional midwifery in the LGA. If adequately trained, equipped, supported and
      supervised, TBAs can contribute towards safe motherhood in Nigeria and in other
      developing countries.

PMID- 11467205
TI  - Lessons to be learned: a case study approach. 'Spontaneous' intraperitoneal
      bladder rupture in a psychiatric patient--with diagnostic difficulties.
AB  - The case described here is that of a 34-year-old woman with a psychiatric
      disorder who was referred to the local surgical receiving unit with abdominal
      pain and vomiting. She remained well and fully mobile but refused blood
      investigations until the day following admission. At that time the tests showed a
      picture of acute renal failure. With the development of increasing abdominal
      tenderness and pyrexia she was persuaded to have a laparotomy which demonstrated
      a small tear at the dome of the bladder. Her deranged blood biochemistry returned
      to normal within 11 h following surgery. The important points demonstrated in
      this case study are the special clinical difficulties encountered in psychiatric
      patients, which may consequently lead to delay in diagnosis. This delay allowed
      significant peritoneal reabsorption of urea and creatinine, which masqueraded as
      'acute renal failure' on biochemical testing. The case also highlights the use of
      procyclidine, commonly used in patients with psychiatric disorders; urinary
      retention is a recognised side effect of this drug--and it is possible that such
      retention together with a minor and hence easily overlooked episode of trauma,
      may have contributed to the patient's condition.

PMID- 11467206
TI  - Historical perspectives on health: medicine 2000 years ago: the case of Qumran
      and other biblical sites.

PMID- 11467207
TI  - Promoting healthy skin.

PMID- 11467208
TI  - Beware of the pitfalls in measuring your own blood pressure.

PMID- 11467209
TI  - Pre-eclampsia: clinical associations and pathological changes.

PMID- 11467210
TI  - Pre-eclampsia: hypotheses.

PMID- 11467211
TI  - Nursing in prisons.

PMID- 11467212
TI  - Aspects of the history of nutrition since 1876.
AB  - Since 1876, developments in nutritional science have followed those in chemistry,
      physiology, biochemistry and medicine. The essential relationship between food
      and body energy has been elucidated. The aetiology of diseases long known in
      human history has been traced to deficiencies of specific nutrients, the
      'vitamins', required in very small amounts. These substances have been isolated,
      identified and synthesised. Research in infant malnutrition has led to the
      recognition that comparatively small changes in biochemical programming during
      growth and development may cause disease later in life. Dietary 'roughage' has
      been found to have significance in disease prevention and prospects for the very
      sick have been improved by the development of alternative feeds. Knowledge of the
      human genome promises exciting new advances for nutrition in relation to public
      health and clinical medicine.

PMID- 11467213
TI  - Changes in public health in South Africa from 1876.
AB  - The present population in South Africa, roughly 43 million inhabitants, is made
      up of Africans (77.2%), whites (10.5%), Coloureds (mixed race) (8.8%) and Indians
      (2.5%). In 1900 the infant mortality rate (IMR) among Africans was 330 per 1,000
      live births; this has now fallen to 50-60. In Soweto, a primarily African city,
      IMR averages 20-25. Life expectancy in the past was only 25-30 years; by 1995,
      this reached 63 years. However, this could fall again due to the rapidly
      spreading HIV/AIDS epidemic. Life expectancy could fall to 40-45 years by 2010
      with the AIDS epidemic being the cause of half of all deaths--a disastrous change
      from the previous relatively commendable public health situation. Formerly, the
      most common causes of deaths in young people were infections, diseases associated
      with malnutrition and gastroenteritis. Adults died almost solely from infections,
      including typhoid, dysentery, malaria and tuberculosis (TB). Even though diseases
      associated with malnutrition are less common today, many infections still remain
      a major problem, particularly TB, which is increasing. As late as 1970, Africans
      who reached 50 years had longer life expectancy than whites due to the low
      prevalences of the chronic diseases of lifestyle. This is no longer so, due to
      the recent rises in non-communicable disorders/diseases, principally obesity in
      women, hypertension, diabetes, stroke and the cancers of prosperity. In the not
      so distant future, the level of control of HIV/AIDS related diseases will be the
      major health/disease regulating factor among Africans. Among white, Coloured and
      Indian populations, there have been falls in the mortality rates of the young
      and, despite rises in lifestyle diseases, increases in life expectancy are
      continuing. For all populations other important public health regulatory factors
      include water supply, sanitation, clinic/hospital services and personal
      environmental factors, employment, dietary pattern and intake, smoking practices
      and alcohol consumption and physical activity, particularly in urban dwellers.
      Unfortunately, public health expenditure, also a highly regulating factor, has
      fallen from 8.2% of the gross domestic product in 1994 to 4.1% in 2000.

PMID- 11467214
TI  - Changes and developments in cancer prevention.
AB  - During the last 125 years, there has been a massive decrease in mortality from
      infectious disease, as a result of improved public health and later as a result
      of antibiotic use. This has led to a consequent increase in life span from less
      than 50 (when cancer is rare) to more than 70 (when cancer is common). As a
      result of these changes, cancer has moved from being a very minor cause of
      mortality in 1876 to one of the two major causes by 2000. During the last century
      theories of the causation of cancer have changed progressively. In the early
      phase the main cause was thought to be environmental contamination with
      carcinogenic chemicals. Later, it was thought that all cancers were caused by
      cancers, then that cancer was caused by a breakdown in immune-surveillance. For
      40 years we have known that tobacco smoke is a major cause of respiratory and
      other cancers, and preventive measures are currently having a dramatic effect on
      male lung cancer mortality. During the last 25 years it has become apparent that
      diet is the other major cause of cancer, but theories have moved steadily from a
      search for causal agents (e.g., too much fat) to protective agents (e.g., too
      little fruit and vegetable). Currently it is accepted that all of the above
      theories contribute to the total cancer risk.

PMID- 11467215
TI  - Time to look beyond just lowering the serum concentration of low density
      lipoprotein--high density lipoprotein levels are also important.
AB  - There is convincing epidemiological evidence indicating that the serum levels of
      high density lipoprotein (HDL) cholesterol are inversely related to the risk of
      vascular events. Similarly, intervention trials, involving healthy populations
      and patients with coronary heart disease (CHD), have shown that raising the serum
      levels of HDL is associated with a significant decrease in the risk of vascular
      events. It follows that serum HDL levels must be considered when assessing risk
      and setting therapeutic goals. Some of the currently available national treatment
      guidelines reflect this view. The present review considers the place of serum HDL
      measurement in the prevention of vascular events.

PMID- 11467216
TI  - [Therapeutic strategies and help in chronic alcoholism].
AB  - Chronical alcoholics are a challenge in therapy, especially if they have an
      adverse course of illness and treatment as well as multiple resulting somatical
      and neurological diseases. In German treatment of alcoholics the term 'chronisch
      mehrfach geschadigte Alkoholkranke' (chronically multiple affected alcoholics)
      has been established, describing patients with severe somatical and psychological
      disorders as well as social, professional, financial or legal problems. Permanent
      or even temporary abstinence is hard to achieve for these patients. They are
      usually found in psychiatric hospitals rather than in addiction wards, but also
      in social services or even prisons. Rehabilitation is possible in mental state
      hospitals that accept patients with dual diagnosis, sometimes even in special
      wards. Psychiatric co-morbidity in alcoholics is often underestimated. This is
      most important for psychotic illness, as well as other psychic diseases. A
      special problem is posed by delinquent patients that often have to be treated
      while in a penal institution. Some of the follow-up studies done on that have
      shown relatively good results in patients in penal institutions, but further
      studies are needed. As of yet, recent treatment options in pharmacotherapy to
      prevent alcoholic relapse are not sufficiently used. Anti-dipsotropics or so
      called anti-craving-agents like acamprosate and naltrexone are primarily given to
      increase the rate of abstinence but could successfully be used in a harm
      reduction strategy (less drinking, shorter relapses).

PMID- 11467217
TI  - [Smoking behavior and alcohol drinking in students in a rural area of East
      Germany].
AB  - The present investigation ("Torgau Study") provides epidemiological information
      on a target population which in the past has hardly been in the focus of health
      promotion activities: the subgroup of children and adolescents of rural regions
      in Eastern Germany. A total survey was conducted that encompassed all classes
      from grade 6 to 10 of all schools in the district of Torgau (Saxony). Together,
      5,925 students in the age range 12 to 16 years participated in this study
      (participation rate: 81.3%). The results provide a differentiated picture of
      their smoking behavior and alcohol use broken down by gender, school-type and
      grade. With respect to smoking the data show that the prevalence of regular
      smokers (i.e., daily smokers) in grade 10 is 41% in the Mittelschule (the school
      type with a stronger vocational orientation) and 29% in the Gymnasium (the school
      type with a university-preparatory curriculum). 51.9% of all students report that
      at least one parent smokes. There is a highly significant association between
      smoking status of the parents and smoking status of their children. The analysis
      of reasons for smoking highlight the stepwise transition into nicotine dependency
      from a psychological perspective. Most of the adolescents (about 80%) know about
      the dangers of passive smoking. However, with increasing age this knowledge loses
      its subjective relevance because dissonance-reducing strategies are applied
      ("doesn't matter"-attitude). Among girls, even in grade 10, there are almost no
      daily alcohol consumers (less than 1%); among boys in grade 10 the rate of daily
      alcohol users is about 8%. The rate of those 10th graders who consume alcoholic
      beverages at least once a week is however 30.6% (girls: 18.7%; boys: 44.2%). The
      longer the alcohol experience the more specific become the social and emotional
      motives for drinking. Altogether, the results suggest that efforts to prevent
      substance misuse in the rural regions of Eastern Germany are as necessary as in
      other regions. But the time has come that innovative approaches of drug
      prevention that are implemented and evaluated mostly in the bigger cities should
      also be started in the rural regions (not only of Eastern Germany), and should be
      adapted to the specific conditions there.

PMID- 11467218
TI  - [Tobacco smoking attributable mortality in Germany].
AB  - OBJECTIVE: The goal of the study is the estimation of mortality rates
      attributable to tobacco smoking (TAM) for the Federal States of Germany. METHODS:
      The 0.5% representative sample of the German population with data about tobacco
      smoking (microcensus 1995) as well as the data about causes of death according to
      ICD from the Federal Office of Statistics are used. On these grounds the
      mortality as well as the smoking prevalence and, on the basis of data of the U.
      S. Department of Health and Human Services, the mortality risks for smokers in
      comparison to never-smokers are estimated. RESULTS: Tobacco-smoking attributable
      mortality rates vary in females from 5.6% to 13.2% in the Federal States, in
      males from 24.3% to 29.2% (age: 35 years or older). Women in the City States show
      the highest TAM rates. The TAM rate for Germany (females and males taken
      together) is 17.0% of the total mortality at an age of 35 years and above.
      CONCLUSION: The data reveal for Germany that tobacco smoking is the most
      preventable health risk.

PMID- 11467219
TI  - [Opinions of staff in the trial phase of standardized documentation of
      complementary psychiatric services].
AB  - A computerised standardised documentation system for non-hospital based
      psychiatric and psychosocial care is being developed in Saxony. A range of non
      hospital based services was involved in the development process. Staff members
      were interviewed concerning their experience in using the documentation system.
      Results showed a critical appraisal by staff members, emphasising particularly
      (a) the investment of time required, and (b) the perceived usefulness of the
      documentation which was considered to be limited. Besides staff members feared
      that data protection issues might be disregarded and that data would be used to
      cut expenditure. Findings are compared with other studies assessing staff
      attitudes towards data collection in mental health services. It is concluded that
      the study adds to the existing evidence of staff scepticism towards computerised
      standardised documentation systems.

PMID- 11467220
TI  - [Record linkage with cryptographic identification data in a population-based
      cancer registry. Development, implementation and error rates].
AB  - BACKGROUND: Population-based cancer registries depend on the completeness of
      their case notification. At present, restrictive legal regulations in Germany
      requesting written informed consent of cancer patients hinder some health
      professionals, for example pathologists, from reporting to cancer registries. New
      cryptographic methods may be used to obtain record linkage based on anonymised
      data. OBJECTIVES: To assess the feasibility of a record linkage in the Munster
      Cancer Registry (EKR-MS) using cryptographic methods as compared to traditional
      methods based on personal identifiers. METHODS: We generated so called control
      numbers--a sequence of 23 alphanumeric signs--for 19 name related characteristics
      employing consecutively two different chiffrations. Record linkage was carried
      out using a semi-automatic computer program (AUTOMATCH) that generates
      probabilities of identity for pairs of case notifiation based on the information
      of control numbers only. Probabilities exceeding present limits lead to automatic
      decisions whereas the remaining linkage has to be decided manually. Plausibility
      based rules helped to considerably reduce the amount of manual decisions.
      RESULTS: We compared traditional and cryptographic record linkage for all new
      reports received in the EKR-MS during 1998 (n = 27,262) against the background of
      n = 101,880 known cases in the registry data base. Setting traditional, text
      based record linkage results to be the reference the cryptographic method
      resulted in a synonomous error (false creation of a new case) of almost 2% and a
      homonymous error (false link to a known case) of less than 0.5%. CONCLUSION:
      Cryptographic methods may be feasible procedures of record linkage in cancer
      registries. The size of the database of the EKR-MS prohibits extrapolation of
      findings to smaller registries. The error rates resulting in slight
      overestimation of disease rates that may seem acceptable. It should be noted
      though that cryptographic data are in many situations prohibitive for further
      epidemiologic research limiting the usefulness of the method exclusively to
      cancer registration under the given legal coercion.

PMID- 11467221
TI  - [Breast cancer mortality in women in the Schleswig-Holstein district 1981 to
      1995].
AB  - The present descriptive study evaluates breast cancer mortality among women in
      the northernmost German Federal State of Schleswig-Holstein over the period from
      1981 to 1995 based on data provided by the Schleswig-Holstein State Office for
      Statistics. Starting from the results of the second Cancer Atlas for the Federal
      Republic of Germany [11], covering the period 1976-1980, breast cancer mortality
      rates rose sharply until the beginning of our investigation. A moderate rise in
      breast-cancer mortality in Schleswig-Holstein continued until the third period
      under investigation (1987-1989), while after that time breast cancer mortality
      decreased again towards the end of the investigation period. In Schleswig
      Holstein as a whole, the mortality rate increased by approximately 12% during the
      last 20 years. When reviewing age-specific breast-cancer mortality for each rural
      district ('Kreis') or, respectively, for each self-administrative town
      (kreisfreie Stadt), different patterns were observed, particularly among younger
      women. In the 40- to 44-year and 45- to 49-year age group a rise in breast cancer
      mortality was observed in several, but not all districts. Mortality patterns do
      not tend to be representative for breast cancer incidence because mortality
      reflects only a small proportion of the women actually suffering from breast
      cancer. The standardised incidence of breast cancer in Germany--calculated on the
      basis of data provided by the Saarland cancer registry--is currently over
      60/100,000 and is thus 2-3 times the mortality rate. However, presently it is not
      possible to evaluate the breast cancer incidence (Schleswig-Holstein) because the
      first population-based cancer registration was initiated only in 1999. In
      contrast to other German Federal States, notification of all cancer cases is
      compulsory in Schleswig-Holstein. A valid analysis of breast cancer incidence
      should be possible in 5-10 years conditional on a registration rate of at least
      90%. Further investigations into the causes of breast cancer should be carried
      out to test specific hypotheses on exposure to risk factors, including nutrition
      and life style to clarify the regional differences observed in this study.

PMID- 11467222
TI  - [HIV prevention in young homosexual men. A medical ethical challenge].
AB  - Although considerable progress in the treatment of patients with AIDS has been
      achieved over the recent years, AIDS remains a non-curative disease. Therefore
      the prevention of new infections with HIV is an important goal for medicine and
      public health. However, during recent years the number of new HIV-infections in
      young gay men increased. New empirical data from the U.S. and the U.K. suggest
      that the traditional prevention methods fail to reach young gay men in Western
      countries who become HIV-infected by unsafe sex within intimate relationships.
      The paper discusses these problems from the perspective of medical ethics. New
      approaches to sex education and prevention of HIV and other sexually transmitted
      diseases are developed and the importance of personal values, responsibility,
      intimacy and emotions are emphasized.

PMID- 11467223
TI  - [Home transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin and beta
      hexachlorocyclohexane?].
AB  - Persons living together with workers who have been exposed to dioxins, furans or
      hexachlorocyclohexane, accumulate increased concentrations of these molecules in
      the blood and in fatty tissue, in comparison with normal people. This result is
      based on an investigation of 14 workers and their female partners. The workers
      had been contaminated with high concentrations of 2,3,7,8-TCDD and moderate
      concentrations of beta-HCH, respectively, in contrast with their female partners
      who had never been exposed to these poisons. Nevertheless, the female partners
      accumulated a significant amount of these molecules, corresponding to 10% of the
      concentrations of their male partners. The origin of this correlation is still
      unknown. As a working hypothesis, we discuss the possibility of molecular
      transfer by clothing and underwear. The clinical consequences of these findings
      are still unclear. Further observations are needed.

PMID- 11467224
TI  - [Assessment of mould pollution in residences in southwest Germany].
AB  - Elevated levels of moulds in homes may represent a risk for development of
      allergies and respiratory diseases. Little is known about the levels of these
      biogenic contaminants in homes in South-West Germany. This paper presents the
      results of a study which was performed between November 1997 and May 1998 in the
      four Sentinel Health Departments in Baden-Wurttemberg (Stuttgart, Mannheim, Kehl
      and Aulendorf/Bad Waldsee). It included 377 households in which children of 10
      years of age resided. Moulds were determined in indoor air, outdoor air,
      household dust from floors and mattresses. Specific home characteristics were
      assessed by questionnaire. The median value of the number of colony forming units
      (CFU) in indoor air was 135 CFU/m3 (range 5-17,000) and in outdoor air 145 CFU/m3
      (range 15-2,900). The median value of CFU/g dust, collected from the floors, was
      15,000 (range 0-700,000) and collected from mattresses was 28,000 (range 1,500
      1,350,000). The data suggest that an indoor-outdoor difference exceeding the
      value of 500 CFU/m3 indicates an elevated mould concentration in indoor air
      compared to background. This value can be discussed as a temporary reference
      value for South-West Germany in the winter season. However, a health assessment
      can not be derived from this value.

PMID- 11467225
TI  - [Value of complementary medicine exemplified by rose-hips].
AB  - Rose-hips develop from blossoms of the wild rose (rosa canina) and are a popular
      natural remedy. Laboratory experiments have shown that rose-hip extract inhibits
      lipid oxidation in vitro and reduces the chemotaxis and chemoluminescence of
      leucocytes. In clinical studies serum CRP- und creatinine level declined in
      healthy subjects and patients with osteoarthritis under rose-hip treatment.
      Additionally patients suffering from osteoarthritis reported that physical
      symptoms declined. Data from a randomised controlled trial indicate not only that
      pain significantly declined but also flexion of the hip improved in the active
      treatment group. The anti-inflammatory properties of rose-hip are useful as a
      natural treatment in patients with osteoarthritis. It remains to be proven which
      of the components are responsible for these effects. There is some evidence that
      in addition to the high vitamin content flavonoids may be actively involved.

PMID- 11467226
TI  - Medicare+Choice: facing an uncertain future.

PMID- 11467227
TI  - Scallen: getting a handle on payment, IT spells success.

PMID- 11467228
TI  - Setting the record straight: physician networking is an effective strategy.
AB  - Case studies of 11 leading integrated delivery systems (IDSs) disclose that,
      despite the widespread perception that integrated health care--and particularly
      the acquisition of physician networks--is a failed strategy, integration can be a
      vibrant and effective strategy if approached properly. The successful case-study
      IDSs have certain attributes in common: many were founded by multispecialty
      clinics; they involve physicians in a partnership role with administrators; and
      the primary purpose of their physician networks is to offer patients convenience
      and broader access to the system, rather than simply to increase referrals to the
      hospital or to compete for capitation contracts. Moreover, all of the IDSs are
      actively pursuing measures to improve the financial performance of their
      physician networks, including closing marginal clinics, improving economies of
      scale, adding ancillary and specialty services, seeking administrative
      procedures, and enhancing information technology capabilities.

PMID- 11467229
TI  - The case against without-cause termination provisions in provider contracts.
AB  - The decision of the California Supreme Court in Potvin v. Metropolitan Life
      Insurance Company, issued in 2000, held that a physician who is eliminated from a
      health plan's network based upon a "without-cause" termination clause in the
      contract nevertheless may be entitled to fair procedure rights. Although the case
      did not explain certain elements of the test of substantial economic power,
      healthcare entities can take precautions in response to the Potvin decision.

PMID- 11467230
TI  - Medicare's outpatient code editor is key to APC payments.
AB  - Since implementation of the outpatient prospective payment system (PPS) in August
      2000, HCFA has used an inadequate communication process to inform providers about
      billing and coding requirements. Numerous program memorandums have been issued to
      communicate changes to the outpatient PPS and even to correct information that
      was provided in previous program memorandums. Providers need to monitor changes
      in outpatient PPS policy by reading the program memorandums posted on HCFA's Web
      site (www.hcfa.org) and through reviewing other informal communications posted to
      the HCFA Web site. In addition, the outpatient code editor (OCE) contains
      information about quarterly APC classification updates. In fact, the OCE is the
      only source of this information in many cases. Because the outpatient PPS differs
      from any other PPS implemented by HCFA, providers should ensure that they have
      all the current information they need to comply with the system's billing and
      coding requirements.

PMID- 11467231
TI  - Calculating pass-through and outlier payments under APCs.
AB  - Medicare's outpatient prospective payment system is based on ambulatory payment
      classifications (APCs) that group services into categories for payment. The
      relative weight of each APC is based on the median operating and capital cost of
      the services within the group based on hospital outpatient claims data for 1996.
      These data, however, do not accurately reflect the cost of innovative medical
      devices, drugs, and biologicals currently in use. To account for these
      developments, the Balanced Budget Refinement Act of 1999 (BBRA) established the
      transitional pass-through payment system to provide additional amounts above the
      applicable APC rate for innovative medical devices, drugs, and biologicals. The
      BBRA also established a cost-outlier adjustment. Successfully calculating
      payments for pass-through and outlier devices requires that financial managers
      have a thorough knowledge of the medical devices, drugs, and biologicals being
      used in their outpatient surgery departments.

PMID- 11467232
TI  - Making the best of corporate integrity agreements.
AB  - Corporate integrity agreements (CIAs) imposed by the Office of Inspector General
      (OIG) of HHS have increased dramatically in the past five years. Healthcare
      organizations that enter into a CIA face burdensome monitoring and reporting
      requirements. However, it may be possible to lessen these burdens by negotiating
      modifications to the CIA's requirements. Organizations that have compliance
      programs in place can negotiate with the OIG to integrate elements of their
      existing compliance programs into the CIA. The organization also should attempt
      to negotiate limiting the scope of the monitoring to include only the area that
      was originally investigated. In addition, it may be valuable to negotiate
      insertion of a clause in the CIA allowing the organization to request
      renegotiation of the terms and duration of certain elements of the agreement
      after the first year, if conditions are met. An organized CIA negotiation process
      may be valuable in obtaining a reduced scope of the procedures required by the
      CIA and preparing the organization to meet its obligations.

PMID- 11467233
TI  - Court upholds application of payment-reduction factor to Part B ancillary
      services.

PMID- 11467234
TI  - Automating attachments: the new HIPAA standard.

PMID- 11467235
TI  - Improving staff satisfaction ensures PFS success.

PMID- 11467236
TI  - Health in Pakistan: challenges and opportunities for academia.

PMID- 11467237
TI  - Tuberculosis at the start of the new millennium: can we fight this plague?

PMID- 11467238
TI  - Acute mountain sickness score and hypoxemia.
AB  - BACKGROUND: Hypoxemia is the immediate consequence of hyobaric hypoxia, which is
      the crucial starting mechanism of acute mountain sickness (AMS). The AMS is
      generally a benign and self-limiting condition which can be prevented by gradual
      ascent. However, ascent rates recommended for prophylaxis of AMS are far slower
      than those attempted during military operations and by climbers. OBJECTIVE: The
      current study was carried out to quantify the relationship between AMS and
      hypoxemia alongwith evaluating the benefits of acetazolamide-dexamethasone
      chemoprophylaxis during acute ascent. SUBJECTS AND METHODS: Twenty-four low
      lander male adults (age mean +/- SE 27.8 +/- 1.24 years) were selected. They were
      grouped in a double-blind fashion into four groups and each group (n = 6)
      received placebo (multivitamin) or acetazolamide (250 mg) or dexamethasone (4 mg)
      or a combined regimen of the two drugs twice daily for 5 days, commencing 24
      hours before ascent. The volunteers reached the altitude of 4578 meters within a
      span of one day. Their AMS symptoms were recorded on modified environmental
      symptoms questionnaire (ESQ), after 24 and 72 hours of ascent. Arterial PO2, SO2
      and PCO2 were measured by GEMSTAT blood-gas analyzer (Mallincrodt-USA). RESULTS:
      The ESQ, AMS-C (cerebral) and AMS-R (respiratory) scores of combined therapy
      group were significantly lower as compared to the other groups on the symptom
      rating scale. The significant finding amongst the volunteers taking acetazolamide
      was mild to moderate diuresis whereas severity of headache was markedly less in
      dexamethasone group. The commonest feature of combined therapy was that none of
      the volunteers complained of headache, dysponea, irritability and more than mild
      disturbance of sleep. The ESQ scores of volunteers were inversely correlated to
      PaO2 and SaO2 after 24 hours of ascent to 4578 meters. CONCLUSION: The study
      concludes that severity of AMS is closely related to hypoxemia and combination
      therapy of acetazolamide-dexamethasone may be effective in preventing AMS.

PMID- 11467239
TI  - Serum lipoprotein (a) in offspring of patients with premature myocardial
      infarction.
AB  - OBJECTIVES: To compare serum Lp(a), lipids: TC, TG and lipoproteins: HDL-C and
      LDL-C levels of offspring with history of paternal myocardial infarction with the
      serum levels in offspring without paternal history of myocardial infarction.
      SETTING: Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre,
      Karachi. METHODS: Thirty offspring between the ages of 8-25 years with the
      history of paternal myocardial infarction were randomly selected from population
      and were matched with offspring having no history of parental myocardial
      infarction. RESULTS: Offspring of fathers who had a myocardial infarction tended
      to have a significantly raised level of Lp(a) (p < 0.001) compared with those
      without parental history. None of the other lipoprotein variables we examined
      exhibited a significant difference between the two groups of subjects.
      CONCLUSION: The offspring of fathers with early myocardial infarction have higher
      mean values of Lp(a) than control subjects suggesting that this lipid variable
      may strongly predispose to CAD.

PMID- 11467240
TI  - Psychiatric comorbidity in substance abuse (opioids).
AB  - OBJECTIVE: To find the prevalence of psychiatric disorders among the opioids
      dependents and to assess the severity of their addiction profile. METHOD: Sample
      comprised of fifty patients admitted in drug treatment and rehabilitation center
      at Psychiatry Department of Lady Reading Hospital, Peshawar, between March to
      August 1997. DSM-IV diagnostic criteria were applied to diagnose substance
      dependence and associated psychiatric morbidity, while Hamilton Depression Rating
      Scale, Hamilton Anxiety Rating Scale and Addiction Severity Index were used to
      assess severity of anxiety, depression and dependence respectively. RESULTS: The
      major co-morbid psychiatric conditions were major depression (30%), personality
      disorder (6%), generalized anxiety disorder (4%), phobic disorder (4%), panic
      disorder (2%), dysthymic disorder (2%). CONCLUSION: The overall findings in this
      study lends support to the hypothesis, that there is substantial psychiatric co
      morbidity amongst the opioid abusers and dependents in our population, as is
      found in studies from the West.

PMID- 11467241
TI  - Salbutamol versus theophylline for wheezy infant.
AB  - OBJECTIVE: To compare the tolerability and efficacy of salbutamol and
      theophylline in treating wheezy infant. DESIGN: This was a prospective parallel
      group study. SETTING AND SUBJECTS: Wheezy infants admitted in paediatric ward of
      Khulna Medical College Hospital from January 1998 to March 1999. MAIN OUTCOME
      VARIABLES: Palatability of drugs, clinical efficacy of drugs and adverse events
      during treatment. RESULTS: Ninety-five patients had undergone this study. Forty
      eight were was in salbutamol group and 47 in theophylline group. Clinical problem
      at the beginning was recurrent wheeze (46.3%), wheeze with fever (32.6%) and
      spasmodic cough (21.1%). Salbutamol was more palatable (P < 0.001) than
      theophylline. However efficacy of both the drugs were nearly equal (P > 0.1).
      Adverse effect was more frequent in theophylline treated children (47.4%) than in
      salbutamol group (24.4%). CONCLUSION: Salbutamol is better tolerated than
      theophylline whereas both the drugs were equally effective for bronchodilation in
      infancy.

PMID- 11467242
TI  - Treatment of tibial diaphyseal fractures with closed flexible intramedullary
      ender nails: 39 fractures followed for a period of two to seven years.
AB  - OBJECTIVE: To assess the efficacy of flexible intramedullary Ender nails for the
      treatment of tibial diaphyseal. MATERIALS AND METHODS: This is a retrospective
      review of patients treated with the Ender Nail for both open and closed tibial
      shaft fractures. Between January 1989 and December 1994, 43 fractures were
      treated with these nails. The configuration of each fracture was determined using
      the Orthopedic Trauma Association classification and the extent of soft tissue
      damage was assessed using the Gustilo and Anderson's classification. Four
      patients were excluded from the study due to inadequate follow-up. There were 27
      closed and 12 open fractures. RESULTS: The average time to union in 34 out of 39
      fractures was 17 weeks. Delayed union and malunion occurred in two patients each
      and superficial wound infection in 1 patient. Nonunion occurred in 5 fractures
      that were all located in the distal 1/3 of the tibial diaphysis. We attribute
      this high rate of non-union to a poor rotational control on the distal fragment
      by these nails. CONCLUSIONS: The Ender nails provide effective fixation for the
      OTA stable class of tibial fractures, where they produce good axial and
      rotational stability by virtue of their three-point fixation. Rotational and
      angular stability should be improved by a supplementary cast immobilization for
      fractures with unstable configuration and those located in the distal third of
      the diaphysis.

PMID- 11467243
TI  - Adolescent's knowledge about AIDS--perspective from Islamabad.
AB  - OBJECTIVE: To study the adolescent student's knowledge and its sources about
      AIDS, and its mode of spread in Islamabad. SETTING: One boys and two girls
      schools in Islamabad. METHODS: A cross-sectional survey was conducted, using an
      anonymous, self-administered, brief Urdu questionnaire which was distributed
      among 100 boys and 182 girls. RESULTS: The response rate was 100% and the average
      age of respondents was 14.6 years in boys and 12 years in girls. Most respondents
      knew about AIDS and reported television as their main source of knowledge. Most
      respondents also correctly believed that AIDS patient can pass on the disease to
      others, however, they had erroneous beliefs about its mode of transmission.
      CONCLUSION: This study testifies to the effectiveness of the successful
      television based health education campaign regarding AIDS in the adolescent boys
      and girls, in Islamabad.

PMID- 11467244
TI  - Localized squamous cell carcinoma of renal pelvis.

PMID- 11467245
TI  - Why a research study needs a design?
AB  - Medical research requires as much attention to management as it does to science.
      Effective research depends first upon the thoughtful statements of purpose and
      objectives, and related research questions. These important initial steps in turn
      drive key decisions regarding study type, plans for analyses and competent
      implementation within bounded timeframes and budgets. The research endeavour
      materializes by selecting appropriate study types based on coherent research
      questions, appropriate data collection, and ultimately concludes by drawing
      inferences on the basis of properly planned analyses. This article reviews these
      principles and inter-relationships.

PMID- 11467246
TI  - Beta blocker eye drops related airway obstruction.
AB  - OBJECTIVE: To assess the awareness among chest physicians, ophthalmologists and
      patients about use of eye drops with particular reference to beta blockers such
      as timolol as an agent of aggravating breathlessness in predisposed subjects.
      DESIGN: Cross-sectional study. METHOD: A survey of 20 chest physicians, 20
      ophthalmologists and 200 patients suffering from obstructive airway disease was
      conducted in 2 hospitals and a welfare center of Karachi from August to September
      1997. RESULTS: The results indicate that ophthalmologists showed more awareness
      than chest physicians regarding use of beta blocker eye drops by patients with
      obstructive airways disease (p = 0.004). Patient awareness was low as well.
      CONCLUSION: There is a need to update doctors and educate general public about
      the side effects of beta blocker eye drops in patients with obstructive airway
      disease.

PMID- 11467247
TI  - Multi-drug resistant tuberculosis.

PMID- 11467248
TI  - Volunteer work and well-being.
AB  - Using two waves of panel data from Americans' Changing Lives (House 1995) (N =
      2,681), we examine the relationships between volunteer work in the community and
      six aspects of personal well-being: happiness, life satisfaction, self-esteem,
      sense of control over life, physical health, and depression. Prior research has
      more often examined the effects of voluntary memberships than of volunteer work,
      has used cross-sectional rather than longitudinal data, and, when longitudinal,
      has emphasized social causation over selection effects. Focusing only on the
      consequences of volunteer work overlooks the antecedents of human agency. People
      with greater personality resources and better physical and mental health should
      be more likely to seek (or to be sought for) community service. Hence, we examine
      both selection and social causation effects. Results show that volunteer work
      indeed enhances all six aspects of well-being and, conversely, people who have
      greater well-being invest more hours in volunteer service. Given this, further
      understanding of self- versus social-selection processes seems an important next
      step. Do positive, healthy people actively seek out volunteer opportunities, or
      do organizations actively recruit individuals of these types (or both)?
      Explaining how positive consequences flow from volunteer service may offer a
      useful counterpoint to stress theory, which has focused primarily on negative
      life experiences and their sequelae.

PMID- 11467249
TI  - Age and the effect of economic hardship on depression.
AB  - The amount of depression associated with economic hardship among adults may
      depend on age. This study tests alternative hypotheses about the interaction. The
      first asserts that the amount of depression associated with economic hardship
      decreases with older age because of maturity and experience. The second, the
      opposite, asserts that the amount increases with older age because of
      increasingly limited future opportunities for recovery. The study analyzes data
      from 2,592 households in the 1995 and 1998 telephone survey of Aging, Status, and
      the Sense of Control (ASOC). Regression analyses find that the amount of
      depression associated with economic hardship decreases with older age, both cross
      sectionally and over time. No model shows an increase with age in the depression
      associated with economic hardship. However, regressions do show that not having
      household wage income or having a disabling or life threatening chronic disease
      increases the depression associated with economic hardship. Those interactions
      somewhat suppress the moderating effect of older age on the association between
      economic hardship and depression.

PMID- 11467250
TI  - Neighborhood disadvantage, stress, and drug use among adults.
AB  - This paper explores the relationships among neighborhood disadvantage, stress,
      and the likelihood of drug use in a sample of adults (N = 1,101). Using the 1995
      Detroit Area Study in conjunction with tract-level data from the 1990 census, we
      find a positive relationship between neighborhood disadvantage and drug use, and
      this relationship remains statistically significant net of controls for
      individual-level socioeconomic status. Neighborhood disadvantage is moderately
      associated with drug related behaviors, indirectly through increased social
      stressors and higher levels of psychological distress among residents of
      disadvantaged neighborhoods. A residual effect of neighborhood disadvantage
      remains, net of a large number of socially relevant controls. Finally, results
      from interactive models suggest that the relationship between neighborhood
      disadvantage and drug use is most pronounced among individuals with lower
      incomes.

PMID- 11467251
TI  - Migration, social support and perinatal health: an origin-destination analysis of
      Puerto Rican women.
AB  - Using pooled origin-destination data from the Puerto Rican Maternal and Infant
      Health Study, we investigate linkages between migration, social support, and
      perinatal health. We document differences in social support between three groups
      of Puerto Rican women: non-migrant women in Puerto Rico, first-generation
      migrants to the U.S. mainland, and mainland-born women. The role of social
      support in producing differences in perinatal health outcomes between the groups
      is assessed. The analysis shows striking differences in social support between
      island and mainland women, but little systematic variation among mainland women
      by generation of U.S. residence. The lower level of social support available to
      mainland women is not reflected in the health outcomes examined, which do not
      generally worsen with migration to the United States (with the exception of
      maternal smoking). Nonetheless, we show that social support has important
      implications for stress, which in turn increases the risk of poor health behavior
      and compromised infant health.

PMID- 11467252
TI  - The impact of childhood abuse and neglect on adult mental health: a prospective
      study.
AB  - This paper examines the impact of three types of victimization in childhood-
      sexual abuse, physical abuse, and neglect--on lifetime measures of mental health
      among adults. In contrast to research that relies on retrospective recall of
      childhood victimization, this work uses a prospective sample gathered from
      records of documented court cases of childhood abuse and neglect in a midwestern
      city around 1970. These subjects were interviewed about twenty years later. In
      addition, this research compares outcomes of the 641 members of the abuse and
      neglect group with a matched control group of 510 persons who did not have
      documented cases of abuse or neglect. The results indicate that men who were
      abused and neglected as children have more dysthymia and antisocial personality
      disorder as adults than matched controls, but they did not have more alcohol
      problems. Abused and neglected women report more symptoms of dysthymia,
      antisocial personality disorder, and alcohol problems than controls. After
      controlling for stressful life events, however, childhood victimization had
      little direct impact on any lifetime mental health outcome. This research
      indicates the importance of adopting an approach that places childhood
      victimization in the context of other life stressors and of prospective changes
      over the life course.

PMID- 11467253
TI  - Social inequalities and exercise during adulthood: toward an ecological
      perspective.
AB  - Grounded in ecological theory, this study examines the association among
      participation in regular vigorous exercise and social status, aspects of
      prominent life settings, interactions between life settings, and more proximal
      individual resources and processes using data from the National Survey of Midlife
      Development in the United States (N = 3,032). Among women, a higher level of
      earnings was associated with more vigorous exercise, yet those women with more
      education had a steeper decline in exercise across adulthood. Among men, those
      with the lowest level of education had the steepest decline in physical activity
      across adulthood, and earnings did not affect exercise patterns. Less
      participation in vigorous exercise among blacks, in contrast to nonblacks, was
      explained by their tendency to live in less safe neighborhoods and having more
      functional health problems. Finally, contextual factors from multiple domains
      were independently associated with participation in regular exercise. Consistent
      with ecological theory, these results suggest that interventions to promote
      exercise habits among adults need to consider the independent and interactive
      effects of multiple contextual factors.

PMID- 11467254
TI  - "Don't write me down": legal, clinical, and risk-management aspects of patients'
      requests that therapists not keep notes or records.
AB  - Although many clinicians have reported anecdotally that patients occasionally ask
      that treatment or evaluation notes or records not be kept, the issue has not been
      addressed in the literature. This article deals with the problems arising from
      patients' requests that their therapists refrain from record keeping, first from
      a legal and regulatory perspective, and then from a clinical perspective. METHOD:
      The authors' consultative experience provides examples of variations on the theme
      of patients' requests not to take notes. RESULTS: While records must usually be
      kept, there exist narrow exceptions to this rule. Risk-management suggestions are
      offered as well. CONCLUSIONS: All such requests should be met first with
      exploration, but limits may have to be set in granting the request.

PMID- 11467255
TI  - Therapeutic empathy with the suicidal wish: principles of therapy with suicidal
      individuals.
AB  - Several principles of therapeutic work with suicidal individuals are described.
      These principles represent different aspects of therapeutic empathy with the
      suicidal wish. They are based on a theoretical model that presents suicide as an
      end result of unbearable mental pain. Mental pain is believed to emerge from
      reciprocal interactions between biochemical imbalances, life stress, personality
      factors, pain-producing inner patterns (e.g., self-hate, sense of being
      dispensable), and facilitators and inhibitors of self-destructive behavior. The
      therapeutic approach is characterized by an empathic experiential encounter with
      the death wish, the pain-producing inner patterns, self-destructive tendencies,
      and the exploration of the most dreadful and frightening inner experiences. An
      empathic attitude toward the wish to die, coupled by an uncompromised
      confrontation of self-destructiveness, can provide the hope of discovering a path
      of compromise with life's difficulties.

PMID- 11467256
TI  - Psychotherapy, biological psychiatry, and the nature of matter: a view from
      physics.
AB  - Biological psychiatry has marginalized psychotherapy, and it is difficult for
      psychotherapists to counter its hegemony. The reductionist/materialist position
      seems incontrovertible and self-evident. An important factor in maintaining this
      stance is the belief that the physical world is understandable, solid,
      unproblematic, especially when compared to the realm of the psychological.
      Developments in quantum and relativity theories, however, cast doubt on that
      belief. They show the fundamental nature of the material world to be problematic,
      enigmatic, paradoxical, impossible to understand or conceptualize in terms of
      everyday experience. This insight weakens the prima facie case for privileging
      the material over the psychological, and alternative (i.e., nonneurobiological)
      approaches to mental health matters should, therefore, be able to compete on an
      equal footing. However, the materialist-reductionist stance is kept in place by
      powerful forces and is well defended; rational arguments alone are unlikely to
      have an impact. This pervasive ideological resistance to rational, often well
      founded critiques of physical reductionism continues to be a major impediment to
      changing the present materialist climate. That resistance has to be addressed
      before any significant shift in orientation can be expected to occur.

PMID- 11467257
TI  - "Selflessness" in the service of the ego: contributions, limitations and dangers
      of Buddhist psychology for western psychotherapy.
AB  - Buddhist psychology has now gained some credence in the West and is starting to
      exert a growing influence both on various areas of medicine and well-established
      Western psychotherapies. We reviewed key texts of both the Eastern and Western
      Buddhist literature, with particular emphasis on recent well-established Western
      authors. The Buddhist concept of "selflessness" is often perceived by Westerners
      as a recommendation for the dissolution of their ego and its propelling forces in
      their competitive societies, instead of an invitation to dispel the artificial
      compactness of their "I." With the notions of "Self" and "No self" placed at the
      interface of Buddhist psychology and Western psychotherapies, this article: (i)
      attempts a description of the pros and cons of the two approaches and (ii) points
      at a probably greater therapeutic potential when the two work hand in hand rather
      than as antagonists. Some of the limitations resulting from such a joint approach
      will also be highlighted.

PMID- 11467258
TI  - Therapist reporting of suspected child abuse and maltreatment: factors associated
      with outcome.
AB  - Several studies have found that making a report of suspected child abuse or
      maltreatment concerning a client in psychotherapy is more likely to have a
      positive outcome for the relationship or to effect no change, than to be
      damaging. The current study examined factors that were associated with outcome.
      Three variables, all of which concerned the client-therapist relationship, were
      found to be important for outcome. The quality of the relationship before the
      report made the greatest contribution to predicting outcome, with stronger
      alliances associated with positive outcome. Also important is the length of time
      in treatment, with longer periods of time related to positive outcome. In
      addition, more effective handling of making the report is related to positive
      outcome in that it differentiated improved from no-change groups. Lastly,
      statistical trends were found both for a relationship between therapist comfort
      in reporting and positive outcome, and for families tending to have more negative
      outcomes than adults in individual treatment or children. This is the first time
      that the examination of factors related to outcome was based upon information
      received from mental health professionals who were confirmed by CPS as reporters
      of suspected child abuse and maltreatment. Findings from this and related studies
      should be incorporated into training programs to ease concerns about the effects
      of reporting on the psychotherapy relationship and to offer guidance about
      factors that could increase positive outcomes. Such training could provide needed
      information to practitioners in reporting situations and enable more complete
      reporting.

PMID- 11467259
TI  - Agitation therapy for antisocial and psychopathic personalities: an outline.
AB  - In this paper, a hypothetical model of agitation therapy for some categories of
      antisocial and psychopathic patients/offenders is presented. Agitation therapy is
      mainly meant for very problematic and aggressive individuals who do not (or
      hardly) respond (in some periods) to any other type of psychotherapy,
      neurofeedback, and/or psychopharmacotherapy. The author makes an attempt to
      develop an adequate model of agitation therapy that makes optimal use of learning
      moments in controlled conflict situations. During agitation therapy the
      aggressive antisocial or psychopathic individual will be exposed to external
      agitation of other patients in a controlled manner in order to increase his/her
      self-knowledge; awareness of his or her intolerable behavior and limitations;
      sublimation of aggression/anger; the willingness (and insight in the necessity)
      to change; feelings of responsibility and emotional, social and moral
      development. Agitation therapy is not intended to be an isolated form of
      psychotherapy, but it may be rather often successful in combination with other
      types of psychotherapy, neurofeedback, and/or psychopharmacotherapy.

PMID- 11467260
TI  - The Masterson Approach with play therapy: a parallel process between mother and
      child.
AB  - This paper discusses a case in which the Masterson Approach was used with play
      therapy to treat a child with a developing personality disorder. It describes the
      parallel progression of the child and mother in adjunct therapy throughout a six
      year period. The unique value of the Masterson Approach is that it provides the
      therapist with a framework and tool to diagnose and treat a child during the
      dynamic process of play. The case describes the mother-child dyad throughout
      therapy. It traces their parallel processes that involve separation,
      individuation, rapprochement, and the recovery of real self-capacities. Each
      stage of treatment is described, including verbal interventions. The child's
      internal affective state and intrapsychic structure during the various stages of
      treatment are illustrated by representative pictures.

PMID- 11467261
TI  - Love, praxis, and desirable therapist qualities.
AB  - Until recently, both love and praxis as therapist qualities have not enjoyed the
      attention they deserve. The components of praxis and the derivatives of love
      (namely, empathy and good-will) are important ingredients of therapeutic
      behavior. They are also capable of promoting mental health. Inculcating the
      trainees with these qualities should become foci of training in psychotherapy.

PMID- 11467262
TI  - Resilience in ambiguous loss.

PMID- 11467263
TI  - Taking a look at your organ procurement program.

PMID- 11467264
TI  - Look-alike, sound-alike drug names.

PMID- 11467265
TI  - How HIPAA affects JCAHO accreditation.

PMID- 11467266
TI  - Engaging physicians in the performance improvement process.

PMID- 11467267
TI  - The death of the personal doctor.

PMID- 11467268
TI  - Public accountability: one rule for practitioners, one for scientists?

PMID- 11467269
TI  - Assessing the value of hospital-in-the-home: lessons from Australia.
AB  - OBJECTIVES: To identify factors that influence the cost-effectiveness of hospital
      in-the-home (HITH) and to discuss the impact of funding arrangements in creating
      incentives or disincentives for the establishment of HITH services. METHODS: A
      review of HITH services in Australia was undertaken. Based on the review, factors
      affecting the relative costs of HITH and conventional care were identified, in
      particular, the effect of funding and organisational arrangements on the
      incentives for managers and providers to choose between HITH and conventional
      care. RESULTS: The review of HITH services identified a wide range of models of
      HITH in Australia. Factors identified as important to the success of HITH
      included demographic and location issues, referral mechanisms, the choice of
      staffing and the management of the programme. However, it was clear that the
      structure of the programme often related to funding arrangements. Issues such as
      'incentive funding', establishment costs and opportunity for cost-shifting were
      identified as being relevant to incentives for the efficient provision of HITH.
      CONCLUSIONS: Evaluations are essential to inform decisions about whether HITH is
      likely to be a viable and cost-effective alternative to inpatient care. However,
      the relative costs of HITH and conventional care will depend on local factors.
      From the point of view of the decision-maker, these will be affected by funding
      and organisational arrangements. Funders must be aware that complex financial
      incentives may mask the true costs of HITH services relative to hospital
      services. They need to ensure that the incentives created by funding arrangements
      are transparent.

PMID- 11467270
TI  - Improving referrals for glue ear from primary care: are multiple interventions
      better than one alone?
AB  - OBJECTIVES: To evaluate the effect of a risk factor checklist and training video
      for general practitioners in reducing inter-practice variation and improving the
      appropriateness of referrals (assessed by their positive predictive value or PPV)
      of patients with suspected otitis media with effusion (OME or 'glue ear') to
      secondary care. METHODS: Fifty general practices (177 practitioners) from the NHS
      Trent region and the West of Scotland were cluster-randomised either to a control
      group (n = 12) or to one of three intervention groups (training video (n = 16),
      checklist (n = 11), or both (n = 11)). Data on all paediatric ear, nose and
      throat (ENT) referrals and diagnostic results at ENT clinics were collected for a
      one-year period pre- and post-intervention. Referral rates for OME and for
      closely related conditions were calculated for children aged 0-15 years, based on
      each practice's list size. PPV was defined as the proportion of referrals
      resulting in bilateral hearing loss > or = 20 dB at the ENT outpatient
      department. RESULTS: There was a significant improvement in the PPV, adjusted for
      patients' waiting time between general practitioner (GP) referral and being seen
      at the ENT department. The improvement in PPV pre- and post-intervention was 15%
      (95% confidence interval, CI: -12.1% to 41.7%) for the practices receiving both
      interventions, compared with a degradation of 20% pre- and post-intervention (95%
      CI: -32.9% to -6.4%) for practices receiving only one intervention and a
      degradation of 34% for those receiving no intervention. CONCLUSIONS:
      Disseminating a risk factor checklist and training video on glue ear to GPs using
      a multi-channel approach can improve the quality of referrals to ENT.

PMID- 11467271
TI  - What makes British general practitioners take part in a quality improvement
      scheme?
AB  - OBJECTIVES: To understand the reasons for the apparent success of a quality
      improvement scheme designed to produce widespread changes in chronic disease
      management in primary care. METHODS: Purposeful sample of 36 primary care staff,
      managers and specialists. Qualitative analysis of 27 interviews in East Kent
      Health Authority area, where, over a three-year period, more than three-quarters
      of general practitioners (GPs) and enrolled in a quality improvement programme
      which required them to meet challenging chronic disease management targets
      (PRImary Care Clinical Effectiveness--PRICCE). RESULTS: Major changes in clinical
      practice appeared to have taken place as a result of participation in PRICCE. The
      scheme was significantly dependent on leadership from the health authority and on
      local professional support. Factors that motivated GPs to take part in the
      project included: a desire to improve patient care; financial incentives;
      maintenance of professional autonomy in how to reach the targets; maintenance of
      professional pride; and peer pressure. Good teamworking was essential to
      successful completion of the project and often improved as a result of taking
      part. The scheme included a combination of interventions known to be effective in
      producing professional behavioural change. CONCLUSIONS: When managerial vision is
      aligned to professional values, and combined with a range of interventions known
      to influence professional behaviour including financial incentives, substantial
      changes in clinical practice can result. Lessons are drawn for future quality
      improvement programmes in the National Health Service.

PMID- 11467272
TI  - Vascular patients' preferences for local treatment: an application of conjoint
      analysis.
AB  - OBJECTIVES: To investigate whether and to what extent vascular patients are
      willing to trade expected health outcomes for improvements in non-health
      benefits, such as the availability of local services, in the provision of
      peripheral vascular surgery. METHODS: Conjoint analysis was used to elicit
      patient preferences via a mailed questionnaire. Respondents were asked to
      consider pairwise descriptions of vascular services described in terms of a
      number of key attributes and asked to indicate which scenario description they
      preferred. Multivariate regression analysis was used to estimate the relative
      importance of the attributes to respondents. RESULTS: Of the 339 patients invited
      to participate, 161 (47%) returned a completed questionnaire, although 36 (11%)
      were found to be internally inconsistent and could not be used, leaving 125 (36%)
      for analysis. An unexpected problem arose with respect to the design of the
      conjoint analysis questionnaire. Specifically, three of the attributes in the
      regression model were found to be collinear. The source of this problem, how it
      was overcome and how it can be avoided in future studies is discussed. The
      results of the regression analysis indicated that the patients who responded had
      a preference for local treatment to the extent that they were willing to incur
      increased risks of perioperative mortality and amputation to receive treatment at
      their local hospital. These results are discussed in connection with those from a
      different study which elicited patient preferences for local treatment using a
      standard gamble technique. CONCLUSIONS: Policy-makers, when considering the
      potential benefits of regionalising health care, should seek to elicit the
      preferences of those patients who will be affected by the reorganisation.

PMID- 11467273
TI  - Public release of information on quality of care: how are health services and the
      public expected to respond?
AB  - Public disclosure of the comparative performance of health care providers has
      been proposed as one mechanism of improving the quality of care. Performance data
      have been made public in the USA for over a decade and the provision of
      comparative information about quality of care is a central feature of current UK
      government health policy. The balance between the advantages and risks of
      pursuing such a policy in publicly funded health service is largely unknown.
      Advocates of public disclosure cite the role that comparative data can play in
      ensuring accountability, shifting the ownership of information (and therefore
      power) from professionals to service users and encouraging improvements in the
      processes and outcomes of care. However, these expectations are not necessarily
      realistic. There is some evidence that the public make little use of comparative
      data and there is a risk that public release may result in a loss of confidence
      in the health system and demoralisation of health service staff. In addition,
      there is a legitimate doubt that any early impact of disclosure will not be
      sustained and that the outcomes will not justify the necessary expenditure. In
      conclusion, we suggest that the theoretical benefits of promoting public
      disclosure as voiced by advocates of the policy may not be realised in practice.

PMID- 11467274
TI  - Explicit and implicit rationing: taking responsibility and avoiding blame for
      health care choices.
AB  - Rationing health care in publicly funded health care systems is becoming more
      challenging because of the growing gap between the possibility of effective
      medical intervention and limited resources. This poses both an economic challenge
      and a political puzzle. On the basis of experience in those systems that have
      adopted a systematic approach to rationing, it can be suggested that the dilemmas
      involved should be addressed by strengthening both the information base to
      support decisions and the institutional framework in which decisions are taken.
      The contribution both of experts and of lay people is needed to inform decision
      making, and the processes adopted need to allow for this as well as being
      transparent and accountable. In practice, rationing is likely to combine explicit
      and implicit decision-making and to result in the exclusion of services at the
      margins and the development of guidelines in the mainstream. The politics of
      rationing may favour muddling through and the evasion of responsibility but this
      will be difficult to sustain in an environment in which public awareness of
      decision-making in health care is growing.

PMID- 11467275
TI  - Decision aids: are they worth it? A systematic review.
AB  - OBJECTIVES: The field of consumer decision support interventions has grown
      rapidly in the last 20 years, particularly since the increased formalization of
      evidence-based decision-making in health care. However, little is known as yet
      about the effect these decision aids have on relevant outcomes. To identify
      outcomes influenced by consumer decision aids (CDAs) and the particular effects
      of CDAs on those outcomes. METHOD: Published reports of randomized controlled
      trials and other designs in English identified from searches of Medline,
      Cancerlit, CINAHL, PsycINFO, Social Science Abstracts, the Cochrane Library and
      Current Contents, and from ancestry searches, hand searches and consultation with
      key informants. Studies were included if consumers were the decision-makers,
      decisions were real and not hypothetical, the intervention met a strict
      definition of a CDA and decisions involved treatment or screening. Data on
      setting, subjects, decision types, decision aid features and outcomes were
      extracted. The validity of each study included was evaluated by two team members.
      Summative ratings were calculated and categorized as high, medium and low.
      RESULTS: Over 500 titles were initially assessed; 96 study reports were obtained
      and screened for inclusion. Twenty-two reports representing 20 studies met the
      inclusion criteria. Eight studies with a low rating were excluded. Results were
      synthesized from the remaining 12 studies. Published studies of CDAs are
      increasing although still few in number. Outcomes such as knowledge and decision
      making processes are influenced by CDAs but effects on treatment preferences, the
      actual decision or other outcomes have yet to be clearly established.
      CONCLUSIONS: Improved outcomes result from the use of CDA in some categories of
      outcome but insufficient evidence exists yet to support improved outcomes in all
      categories or to evaluate whether, given the considerable costs of many CDAs,
      funding for extensive ongoing development and testing can be sustained.

PMID- 11467276
TI  - Establishment of a conceptual base for health services research.

PMID- 11467277
TI  - Money or your life? The health-wealth trade-off in pharmaceutical regulation.
AB  - For decades the development of pharmaceuticals has been regulated by safety,
      efficacy and quality rules for product registration. In public health care
      systems, these three 'hurdles' are increasingly being supplemented by a fourth:
      the mandatory requirement to demonstrate economic efficiency in order to obtain
      reimbursement. This requirement challenges the wealth creation ethic of industry
      (money) with the population health ethic of public health and health economics
      (your life). Despite practical and methodological obstacles to the use of
      economic evidence in decisions, the logic of this development is evident: in
      order to maximise improvements in population health, scarce resources must be
      targeted towards developing and applying technologies that deliver the greatest
      health gains per unit cost. The impact of this policy change on industry practice
      and profits will be considerable, and companies that fail to demonstrate the
      economic efficiency of their products will stumble at the fourth hurdle.

PMID- 11467278
TI  - [Delivery in multiple pregnancies].
AB  - BACKGROUND: A knowledge of clinical physiognomy in pathologies related to
      multiple births is indispensable for improving maternal and feto-neonatal
      prognosis. This study is a contribution to the solution of this problem. METHODS:
      A meta-analysis of data for multiple births at Department B of the Gynecology and
      Obstetrics Clinic at the University of Turi during the decade 1989-1998 was
      carried out, focusing on the arrangement and presentation of fetuses, the various
      types of birth, the gestational age at which birth occurred, the weight of
      neonates, neonatal mortality and maternal morbidity. RESULTS: Out of 11,523
      births, there were a total of 194 (1.68%) multiple births, including 190 sets of
      twins and 4 triplets. 154 (79.38%) premature births were reported; 20 occurred
      <32(nd) week (10.29%). There was a high incidence of podalic presentation
      (26.30%) and shoulder presentation (5.61%) among twins; 202 were delivered using
      a cesarian section (51.53%) and 190 by vaginal birth (48.47%), of which 172
      (90.52%) spontaneously. Surgical birth was an important means of extracting
      fetuses rapidly from a pathological environment. two hundred and sixty-two
      neonates (66.84%) were LBW (<2500 g), including 28 (7.14%) VLBW (>1500 g). The
      perinatal mortality rate was 3.82%. Maternal complications mainly occurred during
      the placental state, in the immediate postpartum and in puerperio. CONCLUSIONS:
      The authors feel that a more careful medical and social assistance, preventive
      hospitalisation, early recognition of the risk, constant monitoring for the
      optimal timing of birth, and lastly, qualified medical assistance during labour
      (expert gynecologist, trained obstetric staff) with other medical personnel
      (anesthetist, neonatal specialist) represent winning strategies to solve the
      problems arising during multiple pregnancies.

PMID- 11467279
TI  - [Influence of anthropometric parameters on bone mineral density. Correlations
      with age and sex].
AB  - BACKGROUND: The aim of the study is to analyse the relationship between bone
      mineral density (BMD) and some anthropometric parameters such as body weight and
      height, body mass index, age and sex. METHODS: This study has been carried out
      between January 1997 and March 2000 in 2839 patients, subdivided into 2679 women
      (mean age 63.2 +/- 11 years; range: 26-86 years) and 160 men (mean age 58.9 +/-
      16.1 years; range: 20-95 years), at the Climatric Unit of the University of
      Catania The assessment of BMD was measured using a DEXA densitometer method
      (TurboScan p-DXA, NIM, Verona, Italy). In all patients with high risk for
      osteoporosis and bone fractures, a statistical analysis of the variance (ANOVA),
      in order to point out the predictivity of these parameters. RESULTS: The results
      of the measurements have confirmed a strong relationship between BMD values and
      sex, age and body constitution. CONCLUSIONS: On the basis of these results, the
      importance is stressed of diagnostic, instrumental and laboratory investigations
      for all patients with and without normal body constitution, in order to analyse
      the bone mineral status and establish an appropriate preventive therapy.

PMID- 11467280
TI  - Takeo Wada Cancer Research Symposium in Chiang Mai.

PMID- 11467282
TI  - Re: Dubrova et al. "Induction of minisatellite mutations in the mouse germline by
      low-dose chronic exposure to gamma-radiation and fission neutrons".

PMID- 11467283
TI  - Current advances in Parkinson's disease.

PMID- 11467284
TI  - Neuronal Ca(2+) signalling: pathways and targets.

PMID- 11467285
TI  - Cost-effectiveness of 3-D cell counting.

PMID- 11467286
TI  - 2-D versus 3-D cell counting--a debate. What is an optical disector?

PMID- 11467287
TI  - Is stereology 'unbiased'?

PMID- 11467288
TI  - Commentary of the paper by Benes and Lange.

PMID- 11467289
TI  - Advanced use of 3-D methods for counting neurons.

PMID- 11467290
TI  - Animal research. Various fallacies persist in vivisection debate.

PMID- 11467291
TI  - An improved fixation technique for fluorescence in situ hybridization for
      preimplantation genetic diagnosis.
AB  - OBJECTIVE: To improve existing preimplantation genetic diagnosis fixation
      techniques. DESIGN: Prospective randomized in vitro study. SETTING: Academic
      medical center. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      The intensity and clarity of fluorescence in situ hybridization (FISH) signals
      and the percentage of successfully fixed blastomeres. RESULT(S): The described
      fixation technique resulted in 100% fixation and 100% adequate FISH signals. Two
      conventional techniques resulted in 94% and 87% fixation, and in adequate FISH
      signals in 81% and 87%, respectively. CONCLUSION(S): This newly developed
      fixation technique simplifies the process of fixation of blastomeres for
      preimplantation diagnosis while essentially eliminating the possibility of losing
      a cell during fixation. It will hopefully allow more IVF programs to offer their
      patients preimplantation genetic diagnosis using the FISH technique.

PMID- 11467292
TI  - Mechanisms for bilateral ectopics after embryo transfer?

PMID- 11467294
TI  - Source of vitrification solution.

PMID- 11467295
TI  - CA 125 and follicle stimulation.

PMID- 11467296
TI  - Leuprolide - as needed.

PMID- 11467298
TI  - Plasma ascorbic acid and risk of heart disease and cancer.

PMID- 11467299
TI  - Plasma ascorbic acid and risk of heart disease and cancer.

PMID- 11467300
TI  - Plasma ascorbic acid and risk of heart disease and cancer.

PMID- 11467301
TI  - Plasma ascorbic acid and risk of heart disease and cancer.

PMID- 11467302
TI  - Observational studies for intervention assessment.

PMID- 11467303
TI  - Laparoscopic renal ablation.

PMID- 11467304
TI  - Bladder neck-sparing radical prostatectomy and positive margins.

PMID- 11467305
TI  - The apparent size of seen objects (Part II), 1859.

PMID- 11467306
TI  - Sphingosine-1-phosphate induces proliferation of astrocytes: regulation by
      intracellular signalling cascades.
AB  - Sphingosine-1-phosphate (S1P) is a potent lysophospholipid mediator mostly
      released by activated platelets. It is involved in several functions in
      peripheral tissues, but its effects in the central nervous system are poorly
      documented. Therefore, we have examined the effects of S1P on the proliferation
      of striatal astrocytes from the mouse embryo. These cells have been found to
      express mRNAs for the S1P receptors, Edg-1 and Edg-3. S1P stimulated thymidine
      incorporation and induced activation of extracellular signal-regulated kinases
      (Erks). Both effects were prevented by U0126, an Erk kinase inhibitor. The S1P
      evoked activation of Erk1 was totally blocked in astrocytes pretreated with a
      combination of either phorbol ester (24 h) and LY294002, or phorbol ester (24 h)
      and pertussis toxin (PTX). Each individual treatment only partially inhibited
      Erk1 activation. This suggests that several separate mechanisms mediate this
      process, one involving protein kinase C and another involving Gi/Go proteins and
      phosphatidylinositol 3-kinase. In contrast, the stimulatory effect of S1P on
      astrocyte proliferation was totally blocked by either PTX or LY294002, but not by
      a downregulation of protein kinase C. S1P dramatically inhibited the evoked
      production of cyclic AMP, a response that was impaired by PTX. Finally, S1P
      stimulated the production of inositol phosphates and increased intracellular
      calcium by mobilization from thapsigargin-sensitive stores. These latter effects
      were mainly insensitive to PTX. Probably, Gi/Go protein activation and
      phosphoinositide hydrolysis are early events that regulate the activation of Erks
      by S1P. Altogether, these observations show that astrocytes are targets for S1P.
      Their proliferation in response to S1P could have physiopathological consequences
      at sites of brain lesions and alterations of the blood-brain barrier.

PMID- 11467307
TI  - Safety of drugs commonly used to treat hypertension, dyslipidemia, and type 2
      diabetes (the metabolic syndrome): part 1.
AB  - The benefits of blood pressure lowering, lipid lowering, and glycemic control on
      morbidity and mortality have been established in major long-term clinical trials.
      The most extensive information is available for diuretics or beta-blockers in
      hypertension, hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase
      inhibitors (statins) in dyslipidemia, and insulin or sulfonylureas in diabetes.
      Other drug classes provide similar improvements in blood pressure, lipid profile,
      and glycemic control, and thereby might be expected to provide comparable long
      term benefits. As a result, national guidelines advocate treating patients
      aggressively in order to achieve control of blood pressure low-density
      lipoprotein (LDL) cholesterol, and blood glucose. The risks associated with drug
      treatment are generally class-specific. Among antidiabetic agents, sulfonylureas
      and insulin are associated with risk for severe hypoglycemia, metformin with risk
      for lactic acidosis, and troglitazone with risk for idiosyncratic hepatocellular
      injury. Similarly, widely used antihypertensive and lipid-lowering agents are
      associated with risk for serious complications, such as angioedema with
      angiotensin-converting enzyme inhibitors, possible increased risk for myocardial
      infarction and cancer with calcium antagonists, and myositis and liver
      dysfunction with statins. Physicians must take an aggressive approach to patient
      management in order to achieve a level of disease control that optimally reduces
      risk for morbidity and mortality. Serious adverse events may occur rarely with
      most drug classes; these events can be minimized by appropriately monitoring or
      selecting patients for treatment.

PMID- 11467308
TI  - Retinal imaging techniques in diabetes.
AB  - Diabetic retinopathy is progressive, and detection early is essential for the
      prevention of blindness. Doppler flowmetry, retinal photography, scanning laser
      ophthalmoscopy, and retinal oximetry measurements may identify proliferative
      disease early. Drawbacks of these methods include lack of compliance, failure to
      refer, and failure to identify disease early. As a result, diabetic retinopathy
      is a leading cause of blindness. Our retinal oximeter measures the blood oxygen
      saturation in the large vessels of the retina near the optic disc. Retinal vessel
      oxygen saturations measured with our instrument are sensitive indicators of blood
      loss and hypoxia in swine. We are generating scientific data that suggests that
      retinal vessel oxygen saturations may be used to identify retinal hypoxia prior
      to changes in retinal vessel architecture. We expect to study humans within the
      next two years, and a clinically useful eye oximeter should be available in the
      near future.

PMID- 11467309
TI  - FDA panel approves Cygnus's noninvasive GlucoWatch.

PMID- 11467310
TI  - Repaglinide dose response? A clinician's viewpoint.

PMID- 11467311
TI  - Allen M. Spiegel, M.D., named Director of NIDDK.

PMID- 11467312
TI  - NIAID spearheads collaborative network for clinical research on immune tolerance.

PMID- 11467313
TI  - Clinical chemistry and clinical toxicology devices advisory panel recommendation
      on Glucowatch.

PMID- 11467314
TI  - User experience with the AIDA interactive educational virtual diabetes patient
      simulator.

PMID- 11467315
TI  - Noninvasive glucose determination by oscillating thermal gradient spectrometry.
AB  - BACKGROUND: Several noninvasive measurement approaches for the determination of
      blood glucose levels have been pursued over the past two decades. There is
      worldwide recognition that an unobtrusive and noninvasive measurement technique
      will better enable the patient with diabetes to obtain information for
      appropriate disease management. Many challenges have so far prevented any
      noninvasive technology from meeting the requirements. METHOD: In this article, we
      describe a novel optical technology that when applied to the human body, provides
      both the sensitivity and the specificity required for acceptance. For human
      tissue, specific wavelength bands in the mid- infrared (IR) region offer
      predominantly single component absorbances and thus, provide the basis for the
      required specificity of an in vivo determination of glucose. It is highly
      desirable to utilize these bands for the development of a practical spectroscopic
      technique. The use of mid-IR absorbance bands requires a methodology that
      accommodates relatively short optical transmission pathlengths. Thermal gradient
      spectroscopy is one suitable methodology. We describe the utilization of optical
      phenomena, which arise during a thermal gradient, in the development of a
      practical instrument. The prototype apparatus is described and results obtained
      from aqueous samples and tissue phantom studies are presented. Furthermore, a
      mathematical derivation is presented in the Appendix, that defines the
      relationship between the optical signals produced and the properties of the
      tissue under analysis.

PMID- 11467316
TI  - Intraocular lens glucose sensor.
AB  - Ocular spectroscopy, which is the use of the eye to monitor optically the
      concentration of metabolites in the body, has been successfully applied to
      monitor aqueous humor glucose concentration. In the United States, 1.7 million
      intraocular lenses are currently implanted yearly. Because patients with diabetes
      are more likely to develop cataracts at an earlier age, a relatively high
      proportion of the patients receiving intraocular lenses have diabetes. Last year,
      110,000 patients with diabetes received intraocular lens implants of various
      materials. We have successfully polymerized a fluorescent complex within a
      hydrogel intraocular lens that responds well to glucose concentration.

PMID- 11467317
TI  - Diabetes: what Americans don't know can kill them.

PMID- 11467318
TI  - Blood glucose dependence of visual flicker threshold.
AB  - BACKGROUND: Published research indicated that fluctuations in blood glucose
      concentration (BGC) change the biochemical balance of the retina and may alter
      the sensitivity of retinal cells. Low-contrast flicker was used in this research
      to measure the changes in sensitivity of the retina accompanying shifts in BGC.
      METHODS: In five subjects without diabetes and four subjects with diabetes,
      simultaneous measurements of flicker thresholds, using a two-alternative, forced
      choice psychometric test, and BGC, were made every 15 to 30 minutes for several
      hours, while BGC was allowed to fluctuate spontaneously. RESULTS: Flicker
      thresholds were found to rise and fall, generally tracking BGC in each subject.
      First-day flicker threshold measurements were used to "calibrate" the method for
      each subject, and subsequent days' measurements were used to infer blood glucose.
      The resulting inferred blood glucose values correlated with BGC measured from
      blood samples in the range of 70 mg/dL to 500 mg/dL with a maximum error of +/
      33% in 97% of the measurements. CONCLUSIONS: The feasibility of using flicker
      sensitivity for monitoring blood glucose levels noninvasively is discussed.
      Improvements in the testing method can potentially reach +/-18% error margin with
      1-minute measurements, according to computer simulations. Devices using a visual
      test would be inexpensive to manufacture and would need no disposable supplies.
      Planned research will assess the long-term stability of flicker threshold
      measurements and will determine the applicability of the technique in diabetic
      retinopathy, in hypoglycemia and in the presence of fatigue and inattention.

PMID- 11467319
TI  - Noninvasive glucose monitoring with optical heterodyne technique.
AB  - A novel optical polarimeter to sense the glucose level in vivo and noninvasively
      has been developed in the Institute of Radiological Science, National Yang Ming
      University. A 30-minute delay between the aqueous glucose and the blood glucose
      was observed in rabbit's eyeball. Currently, aqueous glucose in low concentration
      is being tested and discussed.

PMID- 11467320
TI  - Performance evaluation of the MiniMed continuous glucose monitoring system during
      patient home use.
AB  - BACKGROUND: The recent availability of a continuous glucose monitor offers the
      opportunity to match the demands of intensive diabetes management with a period
      of equally intensive blood glucose monitoring. The present study evaluates the
      performance of the MiniMed continuous glucose monitoring system (CGMS) in
      patients with diabetes during home use. METHODS: Performance data and demographic
      information were obtained from 135 patients who were (mean +/- SD) 40.5+/-14.5
      years old, had an average duration of diabetes of 18.0+/-9.8 years, 50% were
      female, 90% were Caucasian, and 87% of whom had been diagnosed with type 1
      diabetes. Patients were selected by their physician, trained on the use of the
      CGMS and wore the device at home for 3 days or more. The performance of the CGMS
      was evaluated against blood glucose measurements obtained using each patient's
      home blood glucose meter. Evaluation statistics included correlation, linear
      regression, mean difference and percent absolute difference scores, and Clarke
      error grid analysis. RESULTS: The CGMS values were compared to 2477 SMBG tests (r
      = 0.91, slope = 0.93, intercept = 14.5 mg/dL, mean absolute difference = 18.0%+/
      19.8%). Clarke error grid analysis showed 96.2% of the data pairs falling within
      the clinically acceptable regions (zones A and B). CONCLUSIONS: These results
      demonstrate the agreement of the CGMS to blood glucose meter values, under
      conditions of home use, in patients selected by their physicians as candidates
      for continuous monitoring. The detailed glucose information provided by the CGMS
      should make successful management of diabetes more easily achieved.

PMID- 11467321
TI  - Noninvasive blood glucose measurements by near-infrared transmission spectroscopy
      across human tongues.
AB  - Noninvasive blood glucose measurements are characterized in human subjects. A
      series of first overtone transmission spectra are collected across the tongues of
      five human subjects with type 1 diabetes. The noninvasive human spectra are
      collected by an experimental protocol that is designed to minimize chance
      correlations with blood glucose levels. In one treatment of the data, every fifth
      sample is used as a blind prediction point to validate model performance. In
      another rearrangement of the data, the spectra collected over the first 29 days
      are used to build calibration models that are then used to predict in vivo
      glycemia from spectra collected over the next 10 days. Of the five data sets (one
      for each subject), one demonstrates a complete inability to predict blood glucose
      levels and is deemed void of glucose-specific information. Glucose-specific
      information is evident in the remaining four data sets, albeit to varying
      degrees. For all data sets, the ability to measure glucose from spectra collected
      noninvasively from human subjects depends on spectral quality and reproducibility
      of the tongue-to-spectrometer interface. The standard error of prediction is 3.4
      mM for the best calibration model. The significance of this magnitude of
      prediction error is discussed relative to the situations where: (1) the model is
      completely void of glucose-specific information and (2) glucose predictions are
      limited by spectral signal-to-noise and sample thickness. Overall, glucose
      specific information is available from noninvasive first-overtone spectra
      collected across human tongues. Significant improvements are necessary, however,
      before clinically useful measurements are possible.

PMID- 11467322
TI  - Continuous glucose monitoring: the next step toward closing the loop.

PMID- 11467323
TI  - Stability of U-10 and U-50 dilutions of insulin lispro.
AB  - BACKGROUND: Insulin lispro, a rapid acting analog of human insulin, has been
      shown to be useful in the treatment of children with diabetes. However, lower
      concentrations of this insulin may be needed to facilitate optimal clinical use.
      Therefore, the stability of insulin lispro when diluted with an appropriate
      diluent was evaluated. METHODS: Insulin lispro (U-100, 100 U/mL) was diluted with
      sterile Neutral Protamine Hagedorn (NPH) diluent to U-10 and U-50. After storage
      for 7, 14, 21, 28, and 32 days at 5 degrees C and 30 degrees C, the diluted
      insulins were analyzed by high-performance liquid chromatography (HPLC) to
      determine potency, purity, polymer, and preservative (metacresol or phenol)
      content in addition to physical appearance and pH determinations. Microbiological
      testing for preservative effectiveness was performed on the U-10 and U-50
      solutions after 32 days at both temperatures. RESULTS: U-10 and U-50 dilutions of
      insulin lispro stored at 5 degrees C and 30 degrees C maintained potency and
      purity throughout the 32-day testing period. Additionally, both control and
      diluted vials maintained antimicrobial effectiveness. CONCLUSION: Insulin lispro
      when diluted with the appropriate diluent demonstrates acceptable stability when
      stored at 5 degrees C and 30 degrees C for a period of 32 days.

PMID- 11467324
TI  - The use of diluted insulin.

PMID- 11467325
TI  - Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic
      effects, and potential clinical utility.
AB  - Type 1 diabetes mellitus (DM) is a disease of insulin deficiency, resulting from
      the autoimmune-mediated destruction of pancreatic beta cells. However, as a
      likely consequence of intraportal insulin deficiency, patients with type 1 DM
      also exhibit abnormalities of the growth hormone (GH)/IGF/IGF-binding protein
      (IGFBP) axis, including GH hypersecretion, reduced circulating levels of insulin
      like growth factor-I (IGF-I) and IGFBP-3, and elevated levels of IGFBP-1. These
      abnormalities not only exacerbate hyperglycemia in patients with type 1 DM, but
      may contribute to the pathogenesis of diabetes-specific complications, including
      diabetic neuropathy, nephropathy, and retinopathy. Therefore, therapeutic
      modalities aimed at restoring the GH-IGF-IGFBP axis are being considered. Herein,
      we review the efficacy of one such therapy, specifically IGF-I replacement
      therapy. To date, short-term beneficial metabolic effects of recombinant human
      IGF (rhIGF)-I therapy have been demonstrated in numerous diabetic conditions,
      including type 1 DM, type 2 DM, and type A insulin resistance. However, the long-
      term safety and metabolic efficacy of rhIGF-I therapy remains to be established.
      Moreover, the potential impact of rhIGF-I on the natural history of diabetic
      complications has yet to be explored.

PMID- 11467326
TI  - Engineering challenges in the development of an encapsulated cell system for
      treatment of type 1 diabetes.
AB  - Implantation of glucose-responsive, insulin-secreting cells is promising in
      providing a treatment for type I diabetes, which is more effective, less
      invasive, and potentially less costly than conventional insulin injections.
      However, in spite of promising results with animal studies, a clinical product or
      therapeutic procedure based on encapsulated cells does not yet exist. This is
      because a number of barriers remain to be addressed, which include a source of
      functional cells, a stable, biocompatible membrane offering immune protection to
      the implant, a construct architecture ensuring cell viability and construct
      function, and the engineering of immune acceptance of the construct post
      implantation. This article reviews these barriers and the current state-of-the
      art, with special emphasis on the engineering challenges involved, and discusses
      possible ways to tackle the complex problems currently preventing this approach
      from reaching clinical practice.

PMID- 11467327
TI  - The promise of technology in the management of the patient with diabetes.
AB  - The advent of technology has brought many improvements in the management of
      individual aspects of the care of the patient with diabetes. However, the best
      management requires communication between systems to enable the clinician to
      coordinate these various aspects. This article reviews examples of the
      application of technology to the individual aspects of care. It also discusses
      the problems and promise of technology to improve overall care management.

PMID- 11467328
TI  - Antibody-targeted immunotherapy for treatment of non-Hodgkin's lymphoma.
AB  - The scientific development of immunotherapies and radioimmunotherapies of cancer
      began more than four decades ago. Over time, it has become apparent that the
      choice of target antigen, immunogenicity of antibodies, length of antibody half
      life, ability of antibodies to recruit immune effector functions, decision on
      conjugation of antibodies to toxins or radionuclides and antibody manufacturing
      are critical components of successful development of an immunotherapeutic
      regimen. Anti-idiotype antibodies were some of the first successful monoclonal
      antibody treatments developed for non-Hodgkin's lymphoma. In 1997, the chimeric
      antibody, Rituximab, was approved by the United States Food and Drug
      Administration for treatment of patients with relapsed or refractory low-grade or
      follicular non-Hodgkin's lymphoma. In an effort to enhance the efficacy of
      immunotherapy, toxins and radionuclides have been conjugated to monoclonal
      antibodies. Ibritumomab, the parent murine antibody of Rituximab, is conjugated
      to the radioisotope 90Y to create 90Y Ibritumomab tiuxetan, (90Y Zevalin, IDEC
      Y2B8). Promising Phase I/II trials have been completed. Phase III experimental
      trials of 9Y Ibritumomab tiuxetan as treatment for relapsed or refractory NHL are
      in progress.

PMID- 11467329
TI  - Controlled delivery of biotechnological products.
AB  - Peptides, proteins, and nucleotides or DNA fragments are the new generation of
      drugs. They are becoming attractive owing to the fast development of
      biotechnology. The admnistration of such molecules, however, may be a problem as
      sensitivity to temperature, instability at some physiological pH values, short
      plasma half-life, and high molecular dimension, which hinders the diffusive
      transport, make, at the moment, parenteral route the only possible way of
      administration of such molecules. Controlled drug delivery that comprises the
      development of new administration routes could be the answer to the problems for
      administration of biotechnological molecules. The rational of drug delivery is to
      change the pharmacokinetic and pharmacodynamic of drugs by controlling their
      absorption and distribution. Rate and time of drug release at absorption site
      could be programmed using a so called delivery system. Different technologies,
      such as chemical (pro-drugs), biological, polymers, lipids (liposomes, LDL), have
      been proposed to obtain controlled drug release. Also the use of new
      administration routes is part of controlled drug delivery. In fact, it could
      increase the drug absorption and reduce the effects of the active ingredient in
      those districts not interested in the therapy. Drug delivery systems allowing for
      an effective release in vivo of new biotechnological molecules, such as
      recombinant antiidiotypic antibodies with antibiotic activity, devoted to the
      treatment of pulmonary (tuberculosis and pneumocystosis) and mucosal
      (candidiasis) diseases are discussed under that perspective.

PMID- 11467330
TI  - Mitochondriotropic cationic vesicles: a strategy towards mitochondrial gene
      therapy.
AB  - The number of diseases found to be associated with defects of the mitochondrial
      genome has grown significantly over the last decade. Despite major advances in
      understanding mtDNA defects at the genetic and biochemical level, there is no
      satisfactory treatment for the vast majority of patients available. This is
      largely due to the fact that almost all mitochondrial DNA defects involve the
      final common pathway of oxidative metabolism making it impossible to bypass the
      defect by giving alternative metabolic carriers of energy. These seemingly
      objective limitations of conventional biochemical treatment for patients with
      detects of mtDNA warrant the exploration of gene therapeutic approaches. However,
      mitochondrial gene therapy still appears only theoretical and speculative. Any
      possibility for gene replacement is dependent on the use of a yet unavailable
      mitochondria-specific transfection vector. Based upon an analysis of the self
      assembly behavior of dequalinium, a cationic single-chain bolaamphiphile which is
      known to selectively accumulate in mitochondria, we have developed a whole new
      strategy for mitochondria-specific DNA delivery. We have succeeded in preparing
      vesicles made of dequalinium, which we termed DQAsomes (U.S. Patent 6,090,619).
      We have shown that DQAsomes efficiently bind and protect DNA and we could
      demonstrate that DQAsome/DNA complexes selectively release DNA at cardiolipin
      rich liposomes mimicking both, the inner and the outer mitochondrial membrane.
      Based on the intrinsic property of dequalinium to preferentially accumulate in
      mitochondria in response to the electrochemical gradient at the mitochondrial
      membrane and based on the selective DNA release at mitochondria-like membranes we
      propose DQAsomes as the first mitochondria-specific vector to deliver DNA to
      mitochondria in living cells.

PMID- 11467331
TI  - N-glycosylation of recombinant pharmaceutical glycoproteins produced in
      transgenic plants: towards an humanisation of plant N-glycans.
AB  - The number of therapeutic proteins successfully produced in plants is steadily
      increasing and is expected to grow even more rapidly in the future. Most
      therapeutic proteins are glycoproteins and N-glycosylation is often essential for
      their stability, folding and biological activity. Recombinant glycoproteins of
      mammalian origin expressed in transgenic plants largely retain their biological
      activity. However, plants are not ideal for production of pharmaceutical proteins
      because they produce molecules with glycans that are not compatible with
      therapeutic applications in humans. As a consequence, strategies to humanise
      plant N-glycans are now developed. Some of these strategies involve the retention
      of the recombinant glycoprotein in the endoplasmic reticulum while others are
      related to the inhibition of endogenous Golgi glycosyltransferases or addition of
      "new" glycosyltransferases. Data on both the N-glycosylation of therapeutic
      glycoproteins produced in transgenic plants and current strategies to humanise
      their N-glycosylation will be discussed in this review.

PMID- 11467332
TI  - Structure alteration of polyketides by recombinant DNA technology in producer
      organisms--prospects for the generation of novel pharmaceutical drugs.
AB  - Actinomycetes are gram-positive bacteria and commercially important
      microorganisms. They are producers of approximately two thirds of all bioactive
      compounds known and they produce a great variety of compounds which have clinical
      application on the basis of their activity against different kinds of organisms
      and cells as antibacterial (macrolides, avermectins), antitumor (anthracyclines,
      angucyclines, aureolic acid group) and also compounds showing immunosuppresant
      activity (rapamycin, FK506). Most of these clinically useful pharmaceuticals
      produced by actinomycetes belong to the polyketide family. Polyketides comprise a
      wide family of chemically diverse compounds, many of which have shown
      bioactivity. The development of recombinant DNA technology has opened a new and
      exciting field of research for the generation of new bioactive compounds through
      genetic manipulation of the biosynthetic pathways. Researchers in this area are
      trying to take advantage of the enormous capability of actinomycetes to produce
      pharmaceutically useful compounds in order to manipulate the different
      biosynthetic pathways and subsequently generate novel drugs. Combinatorial
      biosynthesis is now emerging as a powerful tool to generate novel families of
      compounds by interchanging secondary metabolism genes between bioactive producing
      actinomycetes. Novel compounds will be the consequence of the concerted action of
      enzymes from different, but related, biosynthetic pathways. Insertional
      inactivation of selected genes and tailoring modification may also produce novel
      compounds that can be useful pharmaceuticals or lead compounds for further
      chemical modification. This minireview will present the state of the art in this
      field showing the different polyketides biosynthetic pathways so far
      characterized and how the identified genes are being used to generate structural
      biodiversity. Emphasis will be made on the polyketide family including type I and
      type II polyketides.

PMID- 11467333
TI  - Recombinant technology in transfusion medicine.
AB  - Recombinant technology in transfusion medicine has really only just begun to have
      large-scale impact. The preparation of blood products, determination of blood
      group phenotype, detection of blood group specific antibodies does not currently
      employ DNA-based methods for their preparation or detection. The detection of
      bloodborne viruses, production of blood grouping reagents and diagnosis of HLA
      polymorphism all include recombinant DNA-based technologies and are beginning to
      impact on routine laboratory life in Transfusion medicine. This review analyses
      the current use of recombinant technology in transfusion medicine, and indicates
      where there is likely to be significant development of this methodology
      (particularly in molecular diagnostics) oven the next decade or so. The impact of
      molecular medicine in the field of transfusion has already begun. Recent
      licensing of thrombopoietin for clinical use may have a profound effect on the
      very high current demand for platelet transfusions. Gene therapy protocols for
      the treatment of haemophilias and other coagulation disorders, and the production
      of recombinant blood products may reshape the demand for clotting factors from
      human plasma. I also consider the potential impact of the exciting technologies
      of DNA arraying and nucleic acid therapeutics in the fields of molecular
      diagnostics and the possible treatment of leukemia respectively.

PMID- 11467334
TI  - The history, mechanism and clinical use of oral 5-fluorouracil derivative
      chemotherapeutic agents.
AB  - The role of oral chemotherapy has been getting expanded because of the potential
      advantage in patients' convenience and better quality of life as well as in cost
      effectiveness as compared with intravenous chemotherapy. In this article, the
      history, mechanism of anti-tumor activity, and clinical use of oral chemotherapy
      using 5-fluorouracil (5-FU) derivative chemotherapeutic agents are reviewed.
      Pharmacological analysis has revealed that 5-FU, a basic chemotherapeutic agent
      widely used against a variety of malignant tumors, shows a time dependent anti
      tumor activity, and that continuous maintenance of 5-FU concentration in blood is
      the optimal method in 5-FU administration. UFT, a combination drug of ftorafur
      (tetrahydrofuranyl-5-fluorouracil, tegafur, FT) and uracil, has been developed to
      have potent anti-tumor activity by maintaining higher 5-FU concentration in blood
      and tumor tissues for a long time. FT is a pro-drug that releases 5-FU
      continuously, and uracil is added to inhibit degradation of the released 5-FU.
      Clinically, oral administration of UFT has proved to be effective as an adjuvant
      therapy after surgery for some malignant tumors such as non-small cell lung
      cancer. Moreover, UFT has proved to be effective for inoperable advanced
      malignancies such as colorectal cancer, especially in combination with leucovorin
      or cisplatin. Recently, S-1, a more active oral 5-FU derivative chemotherapeutic
      agent has been developed in Japan. Several factors to affect anti-tumor effects
      and/or toxicities of 5-FU and the derivatives, such as thymidylate synthase
      activity, dehydropyrimidine dehydrogenase activity and p53 status, are also
      discussed in the article. In conclusion, oral administration of 5-FU derivatives
      such as UFT may have several clinical advantages over intravenous 5-FU
      administration.

PMID- 11467335
TI  - Characterization of protein and peptide stability and solubility in non-aqueous
      solvents.
AB  - Small molecule parenterals have often been formulated as solutions or suspensions
      in non-aqueous conditions, however, this technology has not found widespread use
      in the formulation of macromolecules. Formulation of proteins and peptides has
      primarily been achieved through aqueous solutions or reconstituted lyophilized
      cakes. The incorporation of non-aqueous techniques has been limited by the lack
      of general applicability. For example, prediction of solubility, chemical
      stability, conformational stability (unfolding/denaturation processes), and
      activity can be difficult. Therefore, macromolecule non-aqueous preformulation
      work must be performed on a case by case basis. In addition, only a few solvents
      are pharmaceutically acceptable. This article reviews the characterization of
      proteins and peptides in a variety of non-aqueous or co-solvent conditions (both
      acceptable and unacceptable for pharmaceutical applications), and discusses the
      applicability of non-aqueous conditions for increasing solubility, stability and
      activity.

PMID- 11467336
TI  - Polymeric contrast agents for medical imaging.
AB  - Synthetic polymers and co-polymers are described, to be used as carriers of
      reporter groups for gamma-, magnetic resonance (MR), and computed tomography (CT)
      imaging. Those compounds include polychelating and amphiphilic polymers and serve
      as key components of various contrast agents. Single terminus-activated
      polychelating polymers were synthesized using poly-L-lysine (PLL) as a main chain
      and chelating moieties (such as diethylene triamine pentaacetic acid or DTPA) as
      side groups. These polymers were used for the modification of diagnostic
      monoclonal antibodies to increase their load with reporter metal atoms. As a
      result, better images within shorter time intervals were obtained in animal
      experiments. The application of liposomes and micelles as carriers for diagnostic
      imaging agents in experimental and clinical medicine is considered. The load of
      liposomes and micelles with contrast agents for gamma- and MR imaging (MRI) was
      sharply increased by using polychelating polymers additionally modified on one
      end with a hydrophobic phospholipid residue to give amphiphilic polymers. Such
      polymers easily incorporate the liposome membrane or micelle core and provide
      better loading of liposomes and micelles with reporter metals and, consequently,
      better and faster imaging of various physiological compartments, such as
      lymphatic and vascular systems. A block-copolymer of methoxy-poly(ethylene
      glycol) (MPEG) and iodine-substituted PLL was synthesized to prepare long
      circulating contrast agent for CT imaging of the blood pool. In the aqueous
      solution, this copolymer forms stable and heavily loaded with iodine (up to 30%
      of iodine by weight) micelles. These micelle were successfully used for CT
      visualization of the vascular network in experimental animals. General trends in
      developing contrast polymers are discussed.

PMID- 11467337
TI  - Oxygen effects on glucose measurements with a reference analyzer and three
      handheld meters.
AB  - Oxygen may affect glucose meter and reference analyzer measurements. We evaluated
      the effects of changes in blood oxygen tension (Po2) on Accu-Chek Comfort Curve
      (Roche Diagnostics, Indianapolis, IN), Precision G, (Abbott Laboratories,
      Bedford, MA) and One Touch II (Lifescan, Milpitas, CA) glucose meter
      measurements, and on Yellow Springs Instruments (YSI) (Yellow Springs, OH)
      reference analyzer measurements. Venous blood drawn from healthy volunteers was
      adjusted to three glucose levels of 80, 200, and 400 mg/dL, each tonometered with
      six different Po2 levels (40, 80, 160, 240, 320, and 400 torr). To quantitate
      oxygen effects on reference analyzer measurements, glucose differences between
      test sample (Po2 changed) and control (Po2 80 torr) were calculated (YSItest
      YSIcontrol). The threshold for determination of oxygen effects was +/-2 SD, where
      2 SD was fro

PMID- 11467338
TI  - Limitations of point-of-care testing.

PMID- 11467339
TI  - In vitro and in vivo degradation of glucose oxidase enzyme used for an
      implantable glucose biosensor.
AB  - BACKGROUND: The degradation of the glucose oxidase (GOD) enzyme, commonly used in
      the construction of glucose sensors has been of concern for scientists for
      decades. Many researchers have found that GOD deactivates over time, mostly due
      to H2O2 oxidation. This decay can lead to the eventual failure of the sensor.
      However, these findings are controversial, because other researchers did not find
      this degradation. METHODS: The goal of this study was twofold. The first goal was
      to evaluate the in vitro and in vivo stability of two commercially available GOD
      enzymes and the second goal was to evaluate Nafion as a protective coating of
      GOD. Crosslinked GOD samples were sandwiched between two 10-microm pore
      polycarbonate membranes (Nafion coated or uncoated) and placed in custom designed
      Lexan chambers. Chambers were then exposed to a total of five different
      environments: Dulbecco's Modified Eagle Medium (DMEM) or phosphate buffered
      saline (PBS) with and without a 5.6-mM glucose concentration, as well as the
      subcutaneous in vivo environment of 12 rats. After a period of up to 4 weeks,
      chambers were retrieved, opened, and tested for enzyme activity using a three
      electrode system. RESULTS: Enzyme activity showed only a slight decrease when
      exposed to DMEM and PBS without glucose. A more dramatic decrease in activity was
      observed in enzymes exposed to PBS and DMEM with 5.6 mM glucose. The in vivo
      environment also caused a significant decrease in enzyme activity, but the
      decrease was lower than for the in vitro environment with glucose conditions.
      CONCLUSION: The presence of glucose in vitro and in vivo led to the production of
      H2O2, suggesting this to be the main agent responsible for enzyme degradation.
      The use of a Nafion coating did not provide any additional protection.

PMID- 11467340
TI  - Immobilized glucose oxidase in implantable glucose sensor technology.
AB  - Glucose oxidase has had a central role in previous glucose sensing methods and is
      key to the development of certain new glucose sensors. The immobilized enzyme is
      specific for glucose and sufficiently long-lived for many sensor applications,
      but new glucose sensing applications may place increased demands on the enzyme.

PMID- 11467341
TI  - A neural network approach for insulin regime and dose adjustment in type 1
      diabetes.
AB  - BACKGROUND: A decision support system based on a neural network approach is
      proposed to advise on insulin regime and dose adjustment for type 1 diabetes
      patients. METHOD: The system consists of two feed-forward neural networks,
      trained with the back-propagation algorithm with momentum and adaptive learning
      rate. The input to the system consists of patient's glucose levels, insulin
      intake, and observed hypoglycemia symptoms during a short time period. The output
      of the first neural network provides the insulin regime, which is applied as
      input to the second neural network to estimate the appropriate insulin doses for
      a short time period. RESULTS: The system's ability in order to recommend on
      insulin regime is excellent, while its performance in adjusting the insulin
      dosages for a specific patient is highly dependent on the data set used during
      the training procedure. CONCLUSIONS: Despite the limitations of computer-based
      approaches, this study shows that artificial neural networks can assist diabetes
      patients in insulin adjustment.

PMID- 11467342
TI  - Genetics of type 2 diabetes: an overview for the millennium.
AB  - Abundant evidence supports a genetic predisposition to both type 2 diabetes and
      the traits that precede diabetes (insulin resistance and insulin secretion).
      Unusual causes of diabetes have been identified, including autosomal dominant,
      single gene forms due to mutations of glucokinase, the hepatocyte nuclear
      factors, and insulin promoter factor 1. Mitochondrial mutations also may cause
      type 2 diabetes, but together these causes explain only a small fraction of type
      2 diabetes. In contrast, up to 10% of type 2 diabetes, at least in Caucasian
      populations, may be autoimmune. Animal models of type 2 diabetes support multiple
      genetic loci. To identify the loci in the remaining 85% of cases, investigators
      have tested candidate genes in known pathways formutations with some success.
      However, no candidate identified to date appears to act as a major susceptibility
      locus. More recently investigators have used linkage approaches to find genes for
      type 2 diabetes and the prediabetic traits of insulin resistance and insulin
      secretion. A locus has now been mapped and potential causative variants
      identified on chromosome 2q, and many other studies are in progress. New genetic
      tools and the anticipated completion of the human genome project will likely
      result in the discovery of yet new genes and pathways that may offer new targets
      for intervention. Whether a better understanding of the pathophysiology can lead
      to earlier prediction and detection or prevention will depend on the magnitude of
      risk conferred by individual genes and particular populations.

PMID- 11467343
TI  - Alpha-lipoic acid: a multifunctional antioxidant that improves insulin
      sensitivity in patients with type 2 diabetes.
AB  - Alpha-Lipoic acid (LA) is a disulfide compound that is produced in small
      quantities in cells, and functions naturally as a co-enzyme in the pyruvate
      dehydrogenase and alpha-ketoglutarate dehydrogenase mitochondrial enzyme
      complexes. In pharmacological doses, LA is a multifunctional antioxidant. LA has
      been used in Germany for over 30 years for the treatment of diabetes-induced
      neuropathy. In patients with type 2 diabetes, recent studies have reported that
      intravenous (i.v.) infusion of LA increases insulin-mediated glucose disposal,
      whereas oral administration of LA has only marginal effects. If the limitations
      of oral therapy can be overcome, LA could emerge as a safe and effective
      adjunctive antidiabetic agent with insulin sensitizing activity.

PMID- 11467344
TI  - Defective function of the proteasome in autoimmunity: involvement of impaired NF
      kappaB activation.
AB  - Type 1 diabetes (also known as insulin-dependent diabetes mellitus or juvenile
      onset diabetes) is usually caused by T cell-mediated autoimmunity, with a
      prediabetic state characterized by the production of autoantibodies specific for
      proteins expressed by pancreatic beta cells. The nonobese patient with diabetes
      (NOD) mouse is a spontaneous model of type 1 diabetes with a strong genetic
      component that maps to the major histocompatibility complex (MHC) region of the
      genome. A specific proteasome defect has been identified in NOD mouse in select
      lymphocytic and monocytic lineages that results from down-regulation of
      expression of the proteasome subunit LMP2, which is encoded by a gene in the MHC
      genomic region. This defect prevents the proteolytic processing required for the
      production and activation of the transcription factor nuclear factor-kappaB (NF
      kappaB), which plays important roles in immune and inflammatory responses, as
      well as increases the susceptibility of the affected cells to apoptosis induced
      by tumor necrosis factor-alpha (TNF-alpha). The novel role of the proteasome in
      dysfunction in autoimmunity is presented and documented to be both tissue and
      developmental stage specific. We propose a role of the proteasome as a step in
      disease pathogenesis and tissue targeting.

PMID- 11467345
TI  - Thiazolidinediones:  a comparative review of approved uses.
AB  - Thiazolidinediones are a powerful and clinically important new class of oral
      antidiabetic agents that act by improving insulin sensitivity. Troglitazone is
      the prototype drug in this class but was withdrawn from the market in March 2000
      due to its association with idiosyncratic hepatotoxicity. Currently two
      thiazolidinediones, rosiglitazone and pioglitazone, are U.S. Food and Drug
      Administration (FDA) approved for treatment of type 2 diabetes. These agents bind
      to and activate peroxisome proliferator-activator receptor gamma (PPAR-gamma) and
      work by altering the expression of genes involved in glucose uptake, glucose
      disposal, and lipid metabolism. The drugs differ in receptor binding and potency
      due to differences in their side chain moieties. These agents are rapidly
      absorbed from the gastrointestinal tract and are metabolized mainly in the liver.
      Rosiglitazone is FDA approved for monotherapy and for use in combination therapy
      with metformin or sulfonylureas. Pioglitazone is FDA approved for monotherapy as
      well as for use in combination therapy with metformin, insulin, or sulfonylureas.
      These drugs may also cause significant changes in plasma lipid concentrations,
      and improved insulin sensitivity may improve ovulatory function and fertility in
      women with polycystic ovary syndrome. The most serious side effect of the
      thiazolidinediones is hepatotoxicity. Although rosiglitazone and pioglitazone
      were not associated with hepatotoxicity in premarketing clinical trials, there
      were two recent case reports of idiosyncratic hepatotoxicity in patients treated
      with rosiglitazone. In addition, these agents may be associated with edema and
      some hematological changes. The purpose of this review is to provide an overview
      of the two currently approved thiazolidinediones and to suggest an approach for
      their safe and rational use.

PMID- 11467346
TI  - AMP-activated protein kinase: possible target for treatment of type 2 diabetes.
AB  - A considerable amount of data have accumulated showing that contraction of muscle
      has an acute insulin-like effect, triggering the uptake of glucose. Chronic
      muscle contraction, as seen in endurance training has effects on insulin
      sensitivity, enhancing the effect of insulin on glucose uptake. Endurance
      training results in an increase in levels of GLUT4 in the muscle. This increase
      in GLUT4 is thought to be responsible in part for the enhancement of insulin
      sensitivity. Recent experiments have demonstrated that acute and chronic effects
      of muscle contraction on glucose uptake and the increase in GLUT4 may be due to
      activation of a protein kinase, AMP-activated protein kinase (AMPK). This kinase
      is activated by the increase in 5'-AMP and the decline in creatine phosphate that
      occur during muscle contraction. Phosphorylated AMPK then presumably
      phosphorylates undefined target proteins, which in turn increase glucose uptake
      and transcription of the GLUT4 gene. Experiments have demonstrated that this
      kinase, normally activated during exercise, can be activated artificially in
      muscle by injecting non-exercising rats with 5-aminoimidazole-4-carboxamide
      riboside (AICAR), an adenosine analog. AICAR is taken up into muscle and
      phosphorylated to form an analog of 5'-AMP. Acute (stimulation of glucose uptake
      into muscle) and chronic (increase in GLUT4) effects of exercise can be
      reproduced by injection of this drug. These observations open the door to the
      possibility of treatment of patients with type 2 diabetes with AMPK activators.

PMID- 11467347
TI  - Future trends in islet cell transplantation.

PMID- 11467348
TI  - Manipulation of pancreatic stem cells for cell replacement therapy.
AB  - The demonstration of the existence of tissue-specific adult stem cells has had a
      great impact on our understanding of stem cell biology and its application in
      clinical medicine. Their existence has revolutionized the implications for the
      treatment of many degenerative diseases characterized by either the loss or
      malfunction of discrete cell types. However, successful exploitation of this
      opportunity requires that we have sufficient know-how of stem cell manipulation.
      Because stem cells are the founders of virtually all tissues during embryonic
      development, we believe that understanding the cellular and molecular mechanisms
      of embryogenesis and organogenesis will ultimately serve as a platform to
      identify factors and conditions that regulate stem cell behavior. Discovery of
      stem cell regulatory factors will create potential pharmaceutical opportunities
      for treatment of degenerative diseases, as well as providing critical knowledge
      of the processes by which stem cells can be expanded in vitro, differentiated,
      and matured into desired functional cells for implantation into humans. A well
      characterized example of this is the hematopoietic system where the discovery of
      erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF), which
      regulate hematopoietic progenitor cell behavior, have provided significant
      clinical success in disease treatment as well as providing important insights
      into hematopoiesis. In contrast, little is known about the identity of pancreatic
      stem cells, the focus of this review. Recent reports of the potential existence
      of pancreatic stem cells and their utility in rescuing the diabetic state now
      raise the same possibilities of generating insulin-producing beta cells as well
      as other cell types of the pancreatic islet from a stem cell. In this review, we
      will focus on the potential of these new developments and how our understanding
      of pancreas development can help design strategies and approaches by which a cell
      replacement therapy can be implemented for the treatment of insulin-dependent
      diabetes which is manifested by the loss of beta cells in the pancreas.

PMID- 11467349
TI  - Can interstitial glucose assessment replace blood glucose measurements?
AB  - Current treatment regiments for individuals depending on exogenous insulin are
      based on measurements of blood glucose obtained through painful finger sticks.
      The shift to minimal or noninvasive continuous glucose monitoring primarily
      involves a shift from blood glucose measurements to devices measuring
      subcutaneous interstitial fluid (ISF) glucose. As the development of these
      devices progresses, details of the dynamic relationship between blood glucose and
      interstitial glucose dynamics need to be firmly established. This is a
      challenging task insofar as direct measures of ISF glucose are not readily
      available. The current article investigated the dynamic relationship between
      plasma and ISF glucose using a model-based approach. A two-compartment model
      system previously validated on data obtained with the MiniMed Continuous Glucose
      Monitoring System (CGMS) is reviewed and predictions from the original two
      compartment model were confirmed using new data analysis of glucose dynamics in
      plasma and hindlimb lymph (lymph is derived from ISF) in the anesthetized dog.
      From these data sets, the time delay between plasma and ISF glucose in dogs was
      established (5-12 minutes) and a simulation study was performed to estimate the
      errors introduced if ISF is taken as a surrogate for blood. From the simulation
      study, the error component resulting from the differences in plasma and ISF
      glucose was estimated to be < 6% during normal day-to-day use in an individual
      with diabetes (error component calculated as the standard deviation of the
      ISF/plasma glucose differences under conditions where the maximal time delay was
      used). This difference is most likely within the variance between arterial and
      venous blood glucose. We conclude that the differences between plasma and ISF
      glucose will not be a significant obstacle in advancing the use of ISF as an
      alternative to blood glucose measurements.

PMID- 11467350
TI  - Biomaterials community examines biosensor biocompatibility.

PMID- 11467351
TI  - Transitioning patients with type 2 diabetes to a fixed combination >
      glyburide/metformin tablet.

PMID- 11467352
TI  - FDA advisers vote against OTC Pravachol.

PMID- 11467353
TI  - FDA panel vetoes OTC version of cholesterol drug.

PMID- 11467354
TI  - House panel takes up Medicare drug bill.

PMID- 11467355
TI  - Interactive educational diabetes simulators: a look to the future.

PMID- 11467356
TI  - Rituximab: the first monoclonal antibody approved for the treatment of lymphoma.
AB  - Rituximab, a genetically engineered monoclonal chimeric antibody, targets the
      CD20 antigen expressed on B cells. It was approved by the US Food and Drug
      Administration on November 26, 1997, for the indication of relapsed or
      refractory, CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma
      (LG/F NHL), and by the European Agency for the Evaluation of Medicinal Products
      on June 2, 1998, for therapy of patients with Stage III/IV, follicular,
      chemoresistant or relapsed NHL. Eight Phase II or II clinical trials in LG/F NHL
      patients have been completed: five single-agent studies and three combination
      studies. Rituximab has a favorable safety profile: most adverse events (AEs) are
      Grade 1 or 2, and the frequency of AEs decrease with subsequent infusions. AEs in
      the combination studies are consistent with those seen with individual agents.
      For evaluable patients in the single-agent studies, overall response rates (ORR)
      ranged from 40% to 60%, median duration of response (DR) ranged from 5.9 to 15.0+
      months, and median time to progression (TTP) ranged from 8.1 to 19.4+ months. For
      evaluable patients in the combination studies, the ORR ranged from 45% to 100%,
      median DR ranged from 11.7+ to 39.1+ months, and median TTP ranged from 12.9+ to
      40.5+ months. Studies in intermediate- and high-grade NHL are ongoing. Long-term
      development plans include evaluating the safety and efficacy of rituximab in
      various types of lymphoma and in combination with other lymphoma regimens. Future
      studies may explore ways to increase rituximab efficacy by upregulating CD20 or
      increasing effector function with different cytokines.

PMID- 11467357
TI  - Inhibition of cellular proliferation by drug targeting of cyclin-dependent
      kinases.
AB  - Abnormal cellular proliferation is associated with the pathology of several
      diseases, including cancer, atherosclerosis and restenosis post-angioplasty.
      Therefore, antiproliferative therapies may be a suitable approach to treat these
      disorders. Candidate targets for such strategies include specific components of
      the cell cycle machinery. Progression through the cell cycle in mammalian cells
      requires the activation of several cyclin-dependent protein kinases (CDKs)
      through their association with regulatory subunits called cyclins. Active
      CDK/cyclin holoenzymes phosphorylate cellular proteins including the
      retinoblastoma susceptibility gene product (pRb) and the related pocket proteins
      p107 and p130. Several compounds have been described that directly or indirectly
      inhibit the activity of CDKs, which results in a suppression of cell growth. In
      this review, we will discuss the use of drugs targeting CDKs and their
      therapeutic application in animal models and clinical trials.

PMID- 11467358
TI  - Use of recombinant human erythropoietin as an antianemic and performance
      enhancing drug.
AB  - The glycoprotein hormone erythropoietin is an essential viability and growth
      factor for the erythrocytic progenitors in the bone marrow. Tissue hypoxia is the
      main stimulus for the synthesis of the hormone in the kidneys and the liver.
      Endogenous erythropoietin and recombinant human erythropoietin (rHu-EPO) are
      similar with respect to their biological and chemical properties except for some
      microheterogeneities in their 4 carbohydrate chains. Generic products and
      alternatives to rHu-EPO are in development. Renal anemia can be corrected by rHu
      EPO in a dose-dependent and predictable way without major side effects apart from
      a possible increase in arterial blood pressure. The optimal target hematocrit
      still needs to be defined. There are rare reports of antibody formation towards
      rHu-EPO in humans. Patients suffering from non-renal anemias may also benefit
      from the prescription of rHu-EPO. The drug has been approved for treatment of
      tumor patients with platinum-induced anemia. The cost-effectiveness and medical
      justification of the administration of rHu-EPO in tumor patients with respect to
      its positive effects on tumor oxygenation, tumor growth inhibition and support of
      chemo- and radiotherapy is still a matter of debate. In surgical patients, the
      pharmacological application of rHu-EPO can increase the yield of blood units in
      autologous blood donation programs and lower the severity and duration of
      postoperative anemia, if applicated some days prior to surgery. While rHu-EPO is
      a godsend in medical practice, its abuse as an performance enhancing drug by
      athletes in endurance sports is an unethical and potentially dangerous procedure.
      Unequivocal methods for detection of rHu-EPO doping still need to be established.

PMID- 11467359
TI  - Growth velocity, final height and bone mineral metabolism of short children
      treated long term with growth hormone.
AB  - Since human recombinant growth hormone (GH) became available a large number of
      short GH deficient and GH-sufficient children have been treated with growth
      hormone. Growth hormone deficient patients have been followed to final height and
      several studies have shown that even when treated with GH from very early on in
      life they tend to end up shorter than their target height. There is, however, a
      clear increase in their growth velocities particularly during the first 4-5 years
      of GH therapy so that patients end up with a height-SD score of aproximately 
      0.8. Recent studies have demonstrated decreased bone mineral densities (BMD) in
      children with growth hormone deficiency, both by areal and volumetric analysis.
      Therapy with growth hormone clearly increases their BMD with an increase in bone
      formation markers, as will be reviewed in detail. Growth hormone therapy of non
      growth hormone deficient short children has increased their growth velocity short
      term, particularly in girls with Turner's syndrome and in children with chronic
      renal insuficiency. Recent final height data by Rosenfeld et al. and by Swedish
      and Dutch groups have demonstrated a gain of 8-12 cm in girls with Turner's
      syndrome treated with GH or with a combination of GH and oxandrolone. Neely et
      al. and we have demonstrated that growth hormone treated prepubertal age girls
      and adolescents with Turner's syndrome have normal BMD and Shaw et al. has
      suggested that they have normal BMD despite GH or estrogen therapy. However, we
      found the BMD of a group of previously GH treated young women with Turner's
      syndrome on estrogen replacement to be decreased compared to both age and gender
      matched controls and to controls of the same weight and pubertal status. Growth
      hormone therapy increases the growth velocity and the final height of children
      with chronic renal insuficiency, particularly in prepubertal children treated
      with GH before dialysis. We have demonstrated how the BMD of these patients,
      which at baseline is low when compared to healthy age matched controls, but
      normal when compared to height and bone age matched controls, increases with
      growth hormone treatment significantly, moreso than in untreated uremic controls
      or in untreated healthy controls paired for height and bone age. Short, slowly
      growing, non growth hormone deficient patients (idiopathic short stature) have
      been treated for prolonged periods of time with GH. We and others have
      demonstrated a clear increase in their growth velocity short term, but
      improvement of their final height remains unclear and controversial. After 4-8
      years of GH treatment, Hintz et al. have found a 5-6 cm increase in final height
      compared to the predicted adult height before beginning therapy, but most
      patients did not reach their target heights. Other studies, however, have found
      no improvement in final height and Kawai et al. even suggests that GH therapy
      diminishes the final height of treated children due to an earlier puberty and a
      shorter pubertal growth spurt. We, have found decreased BMD in children with
      idiopathic short stature when compared to controls of their same height and bone
      age with a significant increase in BMD following 12 months of GH and with an
      increase in bone turnover as measured by bone formation and resorption markers.
      Recent short term studies in patients with hypophosphatemic rickets and
      osteogenesis imperfecta treated with rhGH have also yielded similar results which
      will be specified in the review. Some 10-20% of children born with intrauterine
      growth retardation (IUGR) end up short and we had already demonstrated 20 years
      ago how 2 years of GH therapy were capable of increasing their growth velocities
      significantly with an improvement of their height-SD scores. Recent studies
      mainly from Europe have corroborated this data long term, so that IUGR children
      have been shown by de Zegher et al. to increase their growth velocities and their
      height for age after 6 years of treatment, entering into the low normal centiles
      of their growth curves for age. Long term studies of these children to final
      height will be necessary to determine the usefulness and safety of this form of
      therapy.

PMID- 11467360
TI  - Advances in biotechnology for tissue engineering of bone.
AB  - Tissue engineering is a rapidly developing field applying the disciplines of cell
      biology, developmental biology, molecular biology and biomimetic engineering to
      regenerate new tissues for replacement therapies in clinical contexts. To aid in
      the elicitation and reiteration of the processes of morphogenesis of tissues, the
      cascade of chemotaxis of progenitor cells, their differentiation and pattern
      formation is redeployed in postnatal tissues, effected by a variety of ever
      increasing morphogens and biomaterials. The extensive recent progress in
      elucidating the molecular biology of BMPs and their receptors shall aid in
      promoting and extending the great operational future of this field. Although the
      BMP family of proteins and osteogenesis have been the subject of several recent
      reviews, we focus here on their activity in primates and on the novel
      localization of BMPs in the cerebellum and other areas of the nervous system, and
      the "mosaicism" of their localisation in the periodontal tissues followed by a
      discussion on the use of BMPs in periodontal regeneration. Lastly, we report on
      the unique osteoinductive activity of TGF-beta proteins in heterotopic sites of
      primates and their synergistic interaction with a recombinant human BMP, and
      finally we present unique data on novel biomaterials endowed with intrinsic
      osteoinductive activity, capable of initiating de novo bone formation in
      heterotopic sites even in the absence of exogenously applied BMPs, and the
      results of a clinical trial in humans using naturally-derived BMPs.

PMID- 11467361
TI  - Transcription factors as potential targets for therapeutic drugs.
AB  - Although drugs which target transcription are in wide therapeutic use, they were
      all identified on the basis of their effect on a specific biological process such
      as inflammation or hormone responses and were only subsequently shown to target
      transcription. Our recent progress in understanding the mechanism of action of
      these drugs and the mechanisms of transcriptional regulation in general offers
      hope for a new generation of drugs isolated on the basis of their ability to
      modulate either the synthesis of transcription factors, the regulation of their
      activity by ligands or phosphorylation events, their protein-protein interactions
      or their binding to DNA.

PMID- 11467362
TI  - Modulation of metabolism through transcriptional control has created new
      treatment opportunities for type 2 diabetes.
AB  - The discovery of the important metabolic and physiological role played by a
      family of transcription factors, the peroxisome proliferator activated receptors
      (PPAR), has opened up for a new understanding of the mode of action for the lipid
      lowering drugs known as fibrates and for the new glucose lowering compounds
      described as insulin sensitizers. Both of these classes of compounds have
      demonstrated significant efficacy in both animal models of the metabolic
      derangements characteristic for type 2 diabetes and in human clinical studies.
      The recognition of the role of these drugs as ligands for PPAR transcription
      factors and the development of new molecular and cellular tools to select and
      characterise new PPAR selective compounds will open up for the development of
      even better new drug candidates for the treatment of metabolic disorders
      associated with type 2 diabetes. With the combined strength of new
      transcriptional mapping technologies developed in the field of molecular biology,
      such as differential mRNA display and DNA microarray hybridisations, it will be
      possible to perform a detailed molecular characterisation of the transcriptional
      events involved in drug actions in cellular and tissue systems, and information
      gathered from such types of analysis will lead to an enormous amount of data,
      from which detailed knowledge of drug actions at the gene regulatory level will
      emerge.

PMID- 11467363
TI  - The chick embryo chorioallantoic membrane as a model for in vivo research on anti
      angiogenesis.
AB  - Anti-angiogenesis, i.e. inhibition of blood vessel growth, is being investigated
      as a way to prevent the growth of tumors and other angiogenesis-dependent
      diseases. Pharmacological inhibition interferes with the angiogenic cascade or
      the immature neovasculature with synthetic or semi-synthetic substances,
      endogenous inhibitors or biological antagonists. The chick embryo chorioallantoic
      membrane (CAM) is an extraembryonic membrane commonly used in vivo to study both
      new vessel formation and its inhibition in response to tissues, cells, or soluble
      factors. Angiogenesis or anti-angiogenesis is evaluated quantitatively or
      semiquantitatively. The fields of application of CAM in the study of anti
      angiogenesis, including our personal experience, are illustrated in this paper.

PMID- 11467364
TI  - Toward the rational design of cell fate modifiers: notch signaling as a target
      for novel biopharmaceuticals.
AB  - Recent advances in our understanding of highly conserved mechanisms that control
      cell fate determination are paving the way towards rationally designed biologics
      that modulate specific cell fate decisions. Cell fate decisions leading to
      proliferation, differentiation or apoptosis are crucial elements in the
      pathogenesis of countless human diseases. Biopharmaceuticals designed to regulate
      such processes in specific cell types in vivo or ex vivo have vast potential
      applications in oncology, stem cell technology, immunomodulation and
      neuropathology. One of the most conserved mechanisms controlling cell fate
      determination is based upon Notch-ligand interactions and subsequent signaling
      events. Recent studies have shown that this mechanism regulates cell
      differentiation, proliferation and apoptosis in a wide variety of cell maturation
      processes and in neoplastic cells. These observations identify the Notch
      signaling network as a promising drug target for numerous indications. In this
      review, we describe: 1) potential drug targets in the Notch signaling network; 2)
      the Notch agonists and antagonists developed so far, including recombinant
      proteins, antibody-based agents, synthetic peptides, antisense oligonucleotides
      and gene therapy approaches, as well as possible strategies to design novel Notch
      targeting biopharmaceuticals; 3) the possible clinical applications of such
      biopharmaceuticals and 4) a model strategy for the selection and developement of
      a Notch-targeting biopharmaceutical.

PMID- 11467365
TI  - Tuberculosis in children: reassessing the need for improved diagnosis in global
      control strategies.
AB  - Pediatric pulmonary tuberculosis (PPTB) remains a major cause of morbidity and
      mortality worldwide, particularly in less developed countries. Current techniques
      are inadequate for diagnosing PPTB. This is an impediment not only for the
      diagnosis and treatment of PPTB cases, but also for epidemiological
      investigations assessing PPTB burden and disease transmission. Causes of
      misdiagnosis of PPTB include non-specific signs/symptoms, low bacillary load,
      recovery methods (sputum or gastric aspirate) for obtaining a clinical sample
      with low bacillary yield, and the inherent low sensitivities of the diagnostic
      tests themselves. New diagnostic and recovery methods have recently been
      evaluated which may provide a means of overcoming some of these obstacles.
      Unfortunately, progress in developing and implementing improved diagnostic tests
      for PPTB has been partially impeded by the very low priority of PPTB in global TB
      control programs based on cost-effective strategies. Regardless of the cost
      effectiveness of diagnosing and treating PPTB, our moral obligation to provide
      access to health care demands that we evaluate and deal with this neglected group
      of patients. Furthermore, recent evidence indicates that PPTB may actually be
      responsible for more disease transmission than previously thought. In this
      review, we present compelling evidence that research agendas and TB control
      programs should be reassessed and possibly revised to deal with the global
      disease caused by PPTB.

PMID- 11467366
TI  - Tuberculosis and patient gender in Bangladesh: sex differences in diagnosis and
      treatment outcome.
AB  - SETTING: The public health sector of Bangladesh. OBJECTIVE: To assess gender
      differences in access to tuberculosis diagnosis and in tuberculosis treatment
      outcome in Bangladesh. METHODS: Information on the age and sex of a sample of
      patients in 1997 was collected from out-patient registers and tuberculosis
      laboratory and treatment registers in 59 thanas in three divisions in Bangladesh.
      RESULTS: The female/male ratio was 0.79 among 42,877 out-patients with
      respiratory complaints, 0.51 among 5,665 tuberculosis suspects undergoing sputum
      smear microscopy, 0.36 among 869 tuberculosis suspects with positive sputum
      smears, and 0.35 among 5,632 patients registered for tuberculosis treatment.
      Treatment was successful (cured or treatment completed) in 86% of female and 84%
      of male patients. CONCLUSION: Women in Bangladesh appear to have less access to
      public out-patient clinics than men, and if they present with respiratory
      symptoms they are less likely to undergo sputum smear examination. If examined,
      women are less likely than men to be smear-positive. No gender bias was observed
      in tuberculosis treatment outcome. It is recommended to focus further research on
      exploration of sex differences in the incidence of respiratory conditions,
      identification of constraints among women in accessing out-patient clinics and
      verification of the quality of sputum submitted by women for examination.

PMID- 11467367
TI  - Active case finding: understanding the burden of tuberculosis in rural South
      Africa.
AB  - SETTING: The Agincourt demographic and health surveillance site in South Africa's
      rural Northern Province. OBJECTIVES: To accurately assess the true burden of
      tuberculosis in a rural sub-district with a known high prevalence of human
      immunodeficiency virus. DESIGN: Data on hospital registrations of tuberculosis
      were combined with data from an ongoing demographic health and surveillance
      system to accurately describe the burden of tuberculosis in a well-defined
      community. Undiagnosed active cases of sputum-positive disease in the community
      were detected among chronic coughers identified by heads of household during a
      single-pass census interview. RESULTS: The incidence of hospitalised tuberculosis
      among the permanently resident population (n = 56 566) was 212/100,000 person
      years during 1999. The average point prevalence of detected tuberculosis (all
      forms) among patients aged over 10 years was 133/100,000, and 81/100,000 for
      sputum-positive pulmonary disease. This compares with a point prevalence of
      16/100,000 cases of sputum-positive disease detected through active case finding.
      CONCLUSION: For every nine cases of sputum positive pulmonary tuberculosis being
      treated at any one time, there are two cases of undiagnosed disease in the
      community. This study demonstrates a modest burden of undiagnosed tuberculosis
      among residents in a rural sub-district in South Africa.

PMID- 11467368
TI  - Assessing health seeking behaviour among tuberculosis patients in rural South
      Africa.
AB  - SETTING: South Africa's rural Northern Province. OBJECTIVES: To examine patterns
      of health seeking behaviour among hospitalised tuberculosis patients. DESIGN:
      Information on personal characteristics, health seeking behaviour and delays to
      presentation and hospitalisation was collected from hospitalised TB patients.
      Analysis of rates was used to investigate factors associated with delay. RESULTS:
      Among 298 patients, median total delay to hospitalisation was 10 weeks, with
      patient delay contributing a greater proportion than service provider delay.
      Patients more often presented initially to public hospitals (41%) or clinics (31
      %) than to spiritual/traditional healers (15%) or private GPs (13%). Total delay
      was shorter amongst those presenting to hospitals than those presenting to
      clinics (rate ratio 1.33, 95%CI 1.13-1.85), with a significantly smaller
      proportion of the total delay attributable to the health service provider (18%
      vs. 42%). Those exhibiting a conventional risk profile for TB (migrants, alcohol
      drinkers, history of TB) were diagnosed most quickly by health services, while
      women remained undiagnosed for longer. CONCLUSION: Considerable delay exists
      between symptom onset and treatment initiation among pulmonary tuberculosis
      patients. While a substantial delay was attributable to late patient
      presentation, an important, preventable period of infectiousness was caused by
      the failure of recognised clinical services to diagnose tuberculosis among
      symptomatic individuals.

PMID- 11467369
TI  - Treatment outcome among Rwandan and Burundian refugees with sputum smear-positive
      tuberculosis in Ngara, Tanzania.
AB  - SETTING: Tuberculosis programme in six camps (Benaco, Musuhura, Lumasi, Lukole,
      Keza and Kitali) for Rwandan and Burundian refugees in Ngara district, Tanzania,
      where treatment was directly observed throughout. OBJECTIVES: To evaluate the
      treatment outcome of sputum smear-positive tuberculosis cases recruited in
      refugee camps in Ngara, and to determine the cumulative frequency of conversion
      of sputum smears by direct microscopy. DESIGN: Retrospective review of
      tuberculosis registers from January 1995 to December 1999. RESULTS: Of 546
      patients with smear-positive tuberculosis who were notified in the programme, 363
      (66.5%) had completed treatment and were bacteriologically cured after 7 months,
      10.9% had died, 7.1% had defaulted and 14.5% had transferred out. Sputum
      conversion after the 2-month intensive phase was 88%, and increased to 99% after
      7 months of chemotherapy. CONCLUSION: The involvement of the Tanzania NTLP in
      collaboration with health NGOs has led to a satisfactory outcome. These data
      suggest that it is possible for tuberculosis control programmes to perform
      successfully in refugee settings.

PMID- 11467370
TI  - Investigation of tuberculosis transmission in Canadian Arctic Inuit communities
      using DNA fingerprinting.
AB  - OBJECTIVE: To understand the transmission of tuberculosis in Inuit communities in
      the Baffin region of the Canadian Arctic. METHODS: Twenty-one isolates of
      Mycobacterium tuberculosis from 19 Inuit patients diagnosed with tuberculosis
      between February 1991 and September 1993 were analyzed by DNA fingerprinting. The
      DNA fingerprints were achieved by the standard restriction fragment length
      polymorphism (RFLP) technique, with subsequent probing using the repetitive
      insertion segment IS6110. RESULTS: The isolates could be divided into three DNA
      types. The DNA types generally corresponded to the geographic origins of the
      patients. In most instances only one DNA type of M. tuberculosis was identified
      in each community. This suggests that a single case was the start of each of the
      three clusters, most likely due to reactivation. CONCLUSIONS: The results show
      that molecular typing of M. tuberculosis was useful in determining the mode of
      transmission of tuberculosis in a remote area of the Canadian Arctic where the
      disease is endemic. In addition, the information provides useful information for
      planning interventions in this setting.

PMID- 11467371
TI  - Occurrence of serious adverse effects in patients receiving community-based
      therapy for multidrug-resistant tuberculosis.
AB  - SETTING: A community-based treatment program for multidrug-resistant tuberculosis
      (MDR-TB) in an urban shantytown of Lima, Peru. OBJECTIVES: To ascertain the
      occurrence of serious adverse effects associated with therapy for MDR-TB in
      northern Lima, Peru, where therapy was individualized according to drug
      susceptibility testing of patients' infecting strains and delivered through a
      community-based program. DESIGN: A retrospective record review of 60 patients who
      had received individualized therapy for MDR-TB between September 1996 and October
      1998. RESULTS: Although adverse effects were common, they occurred less
      frequently than previously reported in the literature and were rarely life
      threatening. Effects occurring most frequently in this population included: mild
      gastritis (100%), dermatological effects (43.3%), peripheral neuropathy (16.7%),
      depression (18.3%), and anxiety (11.7%). These effects never resulted in the
      discontinuation of anti-tuberculosis therapy, and only occasionally resulted in
      the suspension of an agent (11.7%). CONCLUSION: In young patients with little
      comorbid disease, multidrug, long-course regimens rarely caused life-threatening
      adverse effects. Common side effects may be managed successfully on an out
      patient basis through a community-based treatment program in conjunction with MDR
      TB experts, even in resource-poor settings. The very low rate of default in this
      cohort offers hope that strategies to manage the adverse effects may reduce the
      incidence of abandonment of therapy and increase rates of cure.

PMID- 11467372
TI  - Skin test reactivity to mycobacterial antigens parallels the phylogenetic
      structure of their genus.
AB  - SETTING: City of Manaus, Amazonas, Brazil. OBJECTIVE: To explore the relationship
      between positivity to tuberculin and other environmental mycobacteria sensitins,
      according to a range of criteria and presence of BCG scar. DESIGN: Dual skin
      testing with tuberculin and four mycobacterial sensitins, and BCG scar recording
      of 1070 schoolchildren aged 7-14. Four criteria for positivity were used: simple
      and dominant, with 5 and 10 mm cut-off points. RESULTS: The standardised
      prevalence of reactions > or = 5 mm for BCG scar negative children was 58.3% for
      Mycobacterium avium, 54.2% for M. scrofulaceum, 26.8% for M. fortuitum, 17.9% for
      M. tuberculosis and 7.6% for M. kansasii. Correlations between tuberculin and
      each sensitin, for BCG scar negative children, were 0.47 for M. avium, 0.53 for
      M. scrofulaceum, 0.60 for M. kansasii and 0.22 for M. fortuitum (all with P <
      0.01). BCG effect was particularly significant for tuberculin (odds ratio = 3.44
      for reactions > or = 5 mm, P < 0.001) and influenced the balance between
      dominant/non-dominant reactions for all sensitins. CONCLUSION: The correlation
      between tuberculin and each sensitin confirmed the separation of the rapidly (M.
      fortuitum) and slowly growing mycobacteria (M. tuberculosis, M. avium, M.
      scrofulaceum and M. kansasii). The influence of BCG on tuberculin reactions was
      more marked than on other mycobacterial sensitins.

PMID- 11467373
TI  - Relationship between IFN-gamma and skin test responsiveness to Mycobacterium
      tuberculosis PPD in healthy, non-BCG-vaccinated young adults in Northern Malawi.
AB  - SETTING: Rural northern Malawi, where vaccination with BCG Glaxo (1077) provides
      protection against leprosy but not against pulmonary tuberculosis. OBJECTIVE: To
      evaluate the patterns of responsiveness to purified protein derivative of
      Mycobacterium tuberculosis (PPD) in terms of delayed type hypersensitivity (DTH)
      and interferon-gamma (IFN-gamma) production. DESIGN: IFN-gamma was measured in 6
      day whole blood cultures diluted 1 in 10, stimulated with PPD RT48, and the
      results compared to the DTH response to PPD RT23. A total of 633 individuals aged
      12 to 28 years, without prior BCG vaccination, were recruited. RESULTS: Overall,
      63% of subjects made a positive IFN-gamma response (defined as >62 pg/ml), and
      37% gave a DTH induration of >5 mm. A strong correlation between skin test and
      IFN-gamma responses was observed, although with interesting exceptions: 13/270
      individuals with zero DTH showed IFN-gamma responses >500 pg/ml, and 7/53
      individuals with >10 mm induration showed IFN-gamma responses < or = 62 pg/ml.
      The prevalence of skin test responsiveness increased with age, and was higher
      among older males than females; age-sex patterns were less clear for IFN-gamma
      production. CONCLUSION: The 6 day IFN-gamma response to PPD correlates well with
      Mantoux skin test induration. The discordant individuals may represent important
      subsets in terms of protective immunity and risk of clinical tuberculosis.

PMID- 11467374
TI  - Screening of tuberculous pleural effusion by discriminant analysis.
AB  - SETTING: Pneumology Department of a 635-bed acute-care teaching hospital in
      Valencia, Spain. OBJECTIVE: To assess the value of discriminant analysis as a
      method of optimizing the discriminant power of routine radiographic features and
      a panel of laboratory parameters including biochemical analyses of pleural fluid
      for differentiation between tuberculous and non-tuberculous pleural effusion.
      DESIGN: A series of 47 variables were retrospectively obtained from the medical
      records of 189 patients with exudative pleural effusion (tuberculous pleurisy, n
      = 78; non-tuberculous pleurisy, n = 111). A backward elimination method was
      applied until the best discriminant function was found. RESULTS: The most
      powerful predictor of tuberculous pleural effusion was a function that consisted
      of four variables, as follows: age (years); tuberculin skin test (mm of
      induration at 48 hours); white blood cell count (cells/mm3); and bloodstained
      exudate (coded as yes = 1, no = 2). This function showed a sensitivity of 90%,
      specificity of 87%, positive predictive value of 83%, negative predictive value
      of 92%, and was able to give an 88% rate of correct classification. CONCLUSION:
      The calculated discriminant function based on the patient's age, peripheral
      leukocyte count, tuberculin skin test and blood in the exudate is a simple, rapid
      and inexpensive method for screening tuberculous etiology in patients with
      pleural effusion.

PMID- 11467375
TI  - Uncommon presentations of tuberculosis: the potential value of a novel diagnostic
      assay based on the Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP
      10.
AB  - SETTING: Leiden University Medical Center, Leiden, the Netherlands. OBJECTIVE: To
      illustrate the potential value of a recently developed diagnostic assay for
      detection of tuberculosis (TB), based on T cell responses to the early secreted
      antigenic target 6 kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10).
      These antigens are Mycobacterium tuberculosis specific because they are expressed
      by M. tuberculosis but absent from M. bovis bacille Calmette-Guerin (BCG) and
      most environmental mycobacteria. In recent studies, the assay had a high
      sensitivity and specificity for detection of active TB. DESIGN: We describe five
      patients with uncommon presentations of tuberculosis, in whom the diagnosis was
      delayed by negative or conflicting results of diagnostic procedures aimed at
      detection of M. tuberculosis and an uninformative tuberculin skin test. IFN-gamma
      production in response to ESAT-6 and CFP-10 by peripheral blood mononuclear cells
      from these patients was evaluated before and during anti-tuberculosis treatment.
      RESULTS: In all five patients, IFN-gamma responses to ESAT-6 and/or CFP-10 were
      above the cut-off level defined in a previous study. During treatment, IFN-gamma
      responses generally increased. CONCLUSION: These results indicate that T cell
      responses to M. tuberculosis-specific antigens have potential diagnostic value
      when TB is suspected and the results of other diagnostic tests are inconclusive,
      especially in BCG-vaccinated individuals.

PMID- 11467376
TI  - Culture-negative tuberculous enterovesical fistula mimicking late urological
      complications after radiotherapy.

PMID- 11467377
TI  - Management of tuberculosis in children.

PMID- 11467378
TI  - Differential diagnosis of small round cervical lymph nodes: comparison of power
      Doppler US with contrast-enhanced CT and pathologic results.
AB  - PURPOSE: The purpose of this study was to differentiate reactive small round
      lymph nodes (SRLNs) from metastases by power Doppler ultrasonography (PD-US) and
      contrast-enhanced CT (CE-CT). MATERIALS AND METHODS: Both PD-US and CE-CT were
      performed in 99 cervical lymph nodes (LNs) with a maximum diameter of 1.5 cm or
      smaller and maximum longitudinal/transverse ratio of 1.5 or smaller in 76
      patients with head and neck cancer. At pathologic examinations, 45 were reactive
      and 54 were metastatic LNs. The vascular patterns on PD-US were classified as
      hilar, avascular, peripheral, and miscellaneous vascular patterns. The
      enhancement patterns on CE-CT were classified as homogeneous, heterogeneous, and
      ring enhancement. RESULTS: On PD-US, the hilar pattern was more frequently
      associated with benignancy (91%) and the peripheral, miscellaneous vascular
      pattern with malignancy (91%). The avascular pattern included both benign (58%)
      and malignant (42%) LNs. On PD-US, accuracy was 85%. On CE-CT, ring enhancement
      showed metastasis (100%), and these LNs showed avascular or peripheral patterns
      on PD-US. On CE-CT, accuracy was 77%. When information on CE-CT results was added
      to PD-US results, the accuracy rate increased significantly, to 94% (p=0.01).
      CONCLUSION: Vascular patterns evaluated with PD-US and enhancement patterns on CE
      CT can characterize SRLNs. For an avascular pattern on PD-US, information on CE
      CT results can significantly increase the accuracy of characterization.

PMID- 11467379
TI  - Computed tomographic staging of esophageal cancer and prognosis.
AB  - The purpose of this retrospective study was to examine whether computed
      tomography (CT)-determined staging of esophageal cancer (EC) has prognostic
      correlation. The results showed a strong relevance of staging of EC by CT to
      survival (p<0.01).

PMID- 11467380
TI  - Hyperoxia-induced acute lung injury using a pig model: correlation between MR
      imaging and histologic results.
AB  - PURPOSE: To correlate MR imaging findings with pathology in experimental
      hyperoxia-induced acute lung injury, which has similar pathology to diffuse
      alveolar damage (DAD). MATERIALS AND METHODS: Seventeen Yorkshire pigs were
      studied. These animals were exposed to more than 80% oxygen for 24, 48, 72, and
      96 hours in a sealed cage. The lungs were removed and inflated with air infused
      through the trachea, and then examined by both MRI and high-resolution CT (HRCT).
      T1-weighted spin-echo (T1WSE), T2-weighted fast (T2WFSE), and half-Fourier
      acquisition single-shot turbo spin-echo (HASTE) sequences were performed.
      RESULTS: Severity in MR findings and signal-to-noise ratios (SNR) on MR images
      were well correlated with pathological scores. CT values were also correlated
      well with pathologic scores. Abnormal SNR values were obtained from a
      pathological score of 5, whereas abnormal CT values were obtained from a
      pathological score of 15. Furthermore, significant differences in SNR were
      observed in each histopathological phase. CONCLUSION: SNRs on MR images were
      superior to CT values in detecting early pathologic changes in DAD. MR study also
      is potentially useful for evaluation of the histopathological phases in acute
      lung injury.

PMID- 11467381
TI  - Results of combined-modality therapy for primary and secondary malignant lymphoma
      of the central nervous system (CNS).
AB  - PURPOSE: We consider that whatever the vital prognosis of secondary CNS lymphoma
      (SCNSL), its local control is as serious as that of primary CNS lymphoma (PCNSL).
      In this study, both the treatment outcomes and local control of patients with
      SCNSL and PCNSL were compared, with the aim of improving the treatment of SCNSL.
      MATERIALS AND METHODS: This study included 11 patients with PCNSL and 14 with
      SCNSL treated from January 1984 to October 1997. PCNSL patients underwent partial
      tumor resection and received systemic chemotherapy. All SCNSL patients received
      systemic chemotherapy, and eight also received intrathecal anticancer drug
      infusion. Nine PCNSL patients and 11 SCNSL patients underwent whole-brain
      radiation therapy with 4-MV photons. Among the SCNSL patients, three patients
      underwent localized-brain irradiation and two patients also received whole-spine
      irradiation. RESULTS: Five-year survival rates were 34% for PCNSL and 33% for
      SCNSL. In SCNSL, survival times after CNS involvement were very short,
      irrespective of treatment. One-year local control rates after CNS irradiation
      were 38% for PCNSL and 14% for SCNSL. Recurrence was mainly found in the cranial
      region, in seven of 11 PCNSL patients and 10 of 14 SCNSL patients. CONCLUSIONS:
      Patients with SCNSL had a poor prognosis, and local control in them was more
      problematic than in patients with PCNSL. It is necessary to develop new combined
      modality therapy for patients with SCNSL,including the participation of a
      radiation oncologist, before the disease becomes progressive.

PMID- 11467382
TI  - MRI findings of a case of uterine tumor resembling ovarian sex-cord tumors
      coexisting with endometrial adenoacanthoma.
AB  - A case of uterine tumor resembling ovarian sex-cord tumors is reported. MRI was
      performed for the staging of the endometrial adenoacanthoma diagnosed by biopsy.
      A well-defined, slightly hyperintense mass with central hypointensity was noted
      in the myometrium on T2-weighted images. Pathological diagnosis of the myometrial
      mass was uterine tumor resembling ovarian sex-cord tumors. The central
      hypointense area was a leiomyomatous component. Adenoacanthoma was also
      confirmed. These features of coexisting tumors correlated well with the MRI
      findings.

PMID- 11467383
TI  - Breast conservation for huge-sized locally advanced breast cancer: a case report.
AB  - A 35-year-old woman with locally advanced stage IIIB breast cancer (medullary
      carcinoma) 12 cm in diameter underwent neoadjuvant chemotherapy consisting of
      three courses of intraarterial infusion [adriamycin (ADR), mitomycin (MMC),
      cisplatin (CDDP), 5-fluorouracil (5FU)] and four cycles of systemic chemotherapy
      (ADR, epirubicin, cyclophosphamide, MMC, CDDP) for three months. The tumor
      markedly diminished after the first course of intraarterial infusion
      chemotherapy, with a 3-cm tumor remaining after the completion of preoperative
      administration. Pathologically complete response was noted in specimens resected
      following breast conservation surgery. Postoperative radiotherapy was added and
      adjuvant chemohormonal therapy was continued for two years. The patient is alive
      without recurrence and has been able to conserve the breast for the past eight
      years, neoadjuvant chemotherapy including intraarterial infusion enabled breast
      conservation treatment even for huge-sized locally advanced breast cancer.

PMID- 11467384
TI  - A case of isolated esophageal cyst in the posterior mediastinum.
AB  - We report a rare case of posterior mediastinal esophageal cyst associated with
      pulmonary anomaly that had no connection with the proper esophagus, on either CT
      or MRI, and suggest including this entity in the differential diagnosis of
      posterior mediastinal masses.

PMID- 11467385
TI  - Contrast medium precipitation in the stomach between contiguous plain and
      contrast CT scans.
AB  - Precipitation of diluted Gastrografin (meglumine sodium amidotrizoate) occurred
      in the stomach during computed tomography (CT) examination in a 43-year-old man
      with fasting. Precipitation was not observed on the initial plain CT scan, but
      was demonstrated on the contrast-enhanced CT scan following the plain CT.
      Hyperacidity in the stomach might be promoted during CT examination and cause
      precipitation between scans.

PMID- 11467386
TI  - Detection of malignant thymoma in primary tumor and metastatic lesions using
      99mTc-tetrofosmin scintigraphy.
AB  - 99mTc-tetrofosmin was developed as a myocardial perfusion imaging agent and can
      also be used to depict tumors. We have experienced five cases of malignant
      thymoma delineated on 99mTc-tetrofosmin SPECT. In one case significant activity
      was clearly detected in the primary tumor and metastatic lesions. In quantitative
      analysis, similar 99mTc-tetrofosmin and 201Tl-chloride uptake ratios were
      obtained (1.95+/-0.57 versus 2.27+/-0.85, respectively; n.s.). The ability of
      99mTc-tetrofosmin to detect malignant thymoma was comparable to that of 201Tl
      chloride. Therefore, 99mTc-tetrofosmin might be a useful tracer for the detection
      of malignant thymoma, although more studies will be required to evaluate its
      diagnostic accuracy.

PMID- 11467387
TI  - Does the sheep mandible relapse following lengthening by distraction
      osteogenesis?
AB  - AIM: Distraction osteogenesis is a technique used to lengthen the shortened
      mandible. However, the long term stability of the distracted mandibular bone is
      not known. The aim of this study was to assess if the sheep mandible relapses
      following lengthening, and to assess the quality of distracted bone up to 1 year
      post lengthening. METHODS: Twenty-four sheep had bilateral external mandibular
      distractors applied, with three sheep as controls. Titanium marker screws were
      positioned both proximal and distal to the distraction zone in all sheep.
      Following a 5 day latency period, the interdental gap was distracted 1 mm/day for
      20 days, with a subsequent 20 day consolidation period. Ante-mortem serial X-rays
      were used to assess for relapse by measuring the distance between the screws. The
      animals were sacrificed at either 3, 6, 9 or 12 months post-distraction. At post
      mortem, the distance between the screws was re-measured. The distracted bone was
      assessed mechanically and histologically. RESULTS: The mean mandibular
      lengthening obtained was 13.2 mm. There was no relapse of the mandible over 12
      months. The distracted bone had attained the strength and stiffness of
      undistracted bone by 6 months post-distraction (p < 0.05). Histological
      evaluation revealed significant amounts of lamellar bone by 6 months post
      distraction. CONCLUSIONS: No relapse occurred for 12 months post distraction
      lengthening. The bone formed following distraction was stable and of good
      quality. These findings lend support to the use of distraction osteogenesis in
      clinical practice.

PMID- 11467388
TI  - MRI-based stereolithographic models of the temporomandibular joint: technical
      innovation.
AB  - A new technique of manufacturing dual-colour stereolithographic models of hard
      and soft tissues of the temporomandibular joint (TMJ) is presented. Sagittal
      T1/PD weighted magnetic resonance (MR) images of joints with and without disc
      displacement were obtained in the closed and open mouth positions. Individual
      interactive contour identification of bony structures and the articular disc
      followed by binary interpolation provided the data for the generation of acrylic
      TMJ models. Three dimensional in vivo visualization of the articular disc in
      relation to bony structures in the closed and open mouth positions allows a new
      perception of normal and pathological TMJ anatomy.

PMID- 11467389
TI  - Outcome of arthroscopic surgery for internal derangement of the temporomandibular
      joint: long-term results covering 10 years.
AB  - OBJECTIVES: To investigate the long-term success (10-year results) of
      arthroscopic surgery of the temporomandibular joint. PATIENTS AND METHOD: A
      survey was undertaken of 37 patients who had been treated with arthroscopic
      surgery for TMJ internal derangement from 1986 to 1990. Thirty-three patients
      responded, of whom 30 were women and three men, whose age at surgery ranged from
      14 to 77 years (mean: 35.1 years). The mean follow-up period was 10 years and 2
      months. All patients rated their pain level on a visual analogue scale (VAS), and
      also recorded pain, jaw dysfunction, and activities of daily living (ADL) before
      surgery, and at the time of the survey. Interincisal opening was self-assessed
      (mm). Pre- and postoperative pain, dysfunction and ADL scores were compared for
      outcome and statistically analyzed with the Student's t-test. RESULTS: Intensity
      of pain as rated on the VAS was significantly reduced from 5.15 to 0.34 (p<0.01).
      Pain, dysfunction and ADL scores also decreased from 8.25 to 1.09, 6.5 to 1.93,
      and 9.1 to 1.32, respectively (p<0.01). At the preoperative examination, 36 of
      the 37 patients showed limited jaw opening of less than 38 mm, reduced to only
      three postoperatively. For the success rate of TMJ surgery, the responding 33
      plus data of one re-operated patient were assessed. Of these, 27 were rated as
      excellent, four as good, and three (including two re-operated patients) as poor.
      The success rate was 83.8% when three patients who did not respond were included
      in the data. CONCLUSION: The long-term, 10 year outcome of TMJ arthroscopic
      surgery was considered to be acceptable and stable when compared with other
      surgical procedures and with the results of previously published middle to long
      term treatment outcome studies.

PMID- 11467390
TI  - Stability of simultaneous maxillary and mandibular osteotomy for treatment of
      class III malocclusion: an analysis of three-dimensional cephalograms.
AB  - PURPOSE: The current investigation was undertaken to study the three-dimensional
      (3-D) stability of simultaneous maxillary advancement and mandibular setback
      using rigid fixation. The study also aimed to analyse the factors involved in
      postsurgical relapse by evaluation of changes in various parameters. PATIENTS:
      Twenty-five cases were evaluated of simultaneous Le Fort I maxillary advancement
      and mandibular setback using rigid fixation. METHODS: Preoperative, immediate and
      6-month postoperative skeletal and dental changes were analysed using 3-D
      cephalograms obtained from biplanar stereoradiography. Maxillary fixation screws
      were used as landmarks to evaluate postoperative stability. RESULTS: The mean
      maxillary advancement was 3.7 mm. Relapse in the sagittal, vertical, and
      transverse planes was not detectable in the maxilla (p > 0.05). However, for an
      average mandibular setback of 5.7 mm, mean mandibular relapse was 1.1 mm or 19.3%
      anteriorly (p < 0.05). Surgical or postsurgical skeletal changes in the maxilla
      had no detectable influence on mandibular relapse (p > 0.05). Vertical
      alterations of the facial skeleton achieved surgically predicted the mandibular
      relapse (R2 = 0.27, p < 0.05). CONCLUSION: Maxillary advancement and vertical
      changes of +/- 2 mm did not influence the postoperative stability of the
      mandible. Relapse of the mandible seems to be influenced mainly by the amount and
      direction of the surgical alteration of mandibular position.

PMID- 11467391
TI  - Development of a static simulator of the mandible.
AB  - Our aim was to build and assess a static mandibular simulator capable of
      reproducing various masticatory exercises as closely as possible to physiological
      situations. Unlike existing devices that reproduce a small number of exercises
      and of muscular bundles, our simulator is able to reproduce all types of effort
      in the sagittal plane and integrates eleven muscular groups considered by the
      majority of authors as being the most important in mastication. The value of our
      simulator arises from its ability to replicate the external forces (including
      muscular traction, intra-articular reaction and resultant forces applied to the
      mandible) as determined in vivo during previous studies. The importance of such a
      versatile simulator, in addition to enabling study of the mechanical behaviour of
      the mandible, is that it greatly enhances evaluation of a possible mathematical
      model by means of finite element analysis. Stages of the development and
      evaluation of this device are described.

PMID- 11467392
TI  - 3-D COSMOS: a new 3-D model based computerised operation simulation and
      navigation system.
AB  - A new three-dimensional (3-D) model based system for preoperative planning,
      simulating the operation and transfer of the operation from 3-D model to patient
      (navigation) is to be introduced. A computer controlled digitizer with specially
      designed software enables 3-D measurement and symmetry analysis on the 3-D model
      with a precision better than 0.01 mm (SD: 0.05 mm, range: -0.2 to +0.04 mm).
      Translocations of the jaws during simulation are electronically registered with
      6D-position sensors and displayed graphically and numerically on the PC screen
      (measurement accuracy 0.01 mm, 0.002 degrees). A precise transfer of positional
      data from the model to the patient in the operating theater is necessary if 3-D
      model operations are to be made. The position transfer (navigation) system to be
      introduced depends on a neurosurgical headframe on the patient, enabling an easy
      and three-dimensionally precise transfer of the planned jaw position to the
      patient. The three-dimensional precision of the positional transfer is 0.05 mm
      (SD: 0.144 mm, range: -0.36 to +0.69 mm). This new method allows for the first
      time exact three-dimensional simulation of operation and precise transfer to the
      patient. Especially in the case of asymmetric malformation and complex
      dysgnathia, the new method facilitates optimal symmetric and aesthetic results.

PMID- 11467393
TI  - Experience with freeze-dried PGLA/HA/rhBMP-2 as a bone graft substitute.
AB  - We investigated bone induction by recombinant human bone morphogenetic protein-2
      in rodents. The purpose of this study was to evaluate the osteoinductive
      potential of a resorbable bone substitute fabricated from freeze-dried
      poly(glycolic acid-co-lactic acid) (PGLA) mixed with hydroxyapatite particles
      incorporated with bone morphogenetic protein-2 in skull defects of rats (FD
      PGLA/HA/rhBMP-2). The FD-PGLA/HA/rhBMP-2 composite or as a control, the FD
      PGLA/HA by itself were implanted in skull defects (psi 8 mm) of rats. The samples
      were harvested at 2 or 4 weeks postoperatively and were studied radiographically
      and histologically. Four weeks after implantation, the FD-PGLA/HA/rhBMP-2 discs
      were completely replaced by newly-formed bone possessing bone marrow. In
      contrast, the defects implanted with FD-PGLA/HA were filled only with fibrous
      connective tissue. The results suggest that the FD-PGLA/HA/rhBMP-2 composite
      could be an optimum bone substitute with osteoinductive potential and could
      function as an alternative bone graft material for autogenous bone in humans.

PMID- 11467394
TI  - Evaluation of the VX2 rabbit auricle carcinoma as a model for head and neck
      cancer in humans.
AB  - INTRODUCTION: This study investigates whether the VX2 carcinoma cell line,
      transplanted into the rabbit auricle, can be used as a head and neck cancer
      model. The biologic behaviour of this model is evaluated, comparing tumour
      transplantation with either tissue pieces or cell suspensions. MATERIAL: Thirty
      six adult NZW rabbits received s.c. injections of VX2-suspensions (Group S) and
      11 rabbits received solid VX2-pieces (Group P) into both auricles. METHODS: In
      Group S, 16 rabbits were sacrificed at various days before (S1) and 15 after (S2)
      the 28th day following transplantation. In the other five rabbits transplantation
      failed. Animals from Group P were sacrificed every 2 weeks after the 28th day. At
      autopsy the size of the primary tumours and of lymph node, lung and other
      metastases were assessed. If transplantation failed, the maximal tumour size and
      the time at which regression took place were recorded. Exponential trend lines
      were used to create growth curves of metastases. Differences between groups were
      evaluated with the chi2 test, correlations between parameters with Kendall's tau.
      RESULTS: The tumour take-rate in Groups S and P was 78% and 59% respectively. The
      maximal size and time at which regression occurred was significantly different,
      amounting to 83 +/- 7 mm2 at 10.4 +/- 1.6 days (Group S) and 243 +/- 30 mm2 at
      20.9 +/- 2.0 days (Group P), respectively. Development of lymph node metastases
      was not different. In Groups P and S2, over 90% of the necks contained lymph node
      metastases. There was a higher incidence of lung metastases in Group S2 when
      compared to Group P (47% vs. 14%) but it was not statistically significant. A
      significant correlation (p<0.05) between weight loss and the size of lung
      metastases was found. CONCLUSION: Transplantation of the VX2-tumour with cell
      suspensions produces a useful head and neck cancer model for locoregional disease
      in which anti-tumour regimens against both the primary and lymph node metastases
      can be tested. Transplantation with tumour pieces is not advised as the take-rate
      is low and spontaneous remissions occur at a late stage.

PMID- 11467395
TI  - The use of Mitek pins in the mandibular lingual releasing approach to oral and/or
      oropharyngeal carcinomas: a technical note.
AB  - Resection of carcinoma of the oral cavity and oropharynx requires adequate
      exposure. The purpose of this paper is to demonstrate the approach employed
      (mandibular lingual releasing approach) for resection of some oral cavity or
      oropharyngeal carcinomas and to point out the indications, advantages,
      complications, and refinements of this technique. The technique was carried out
      on 23 patients with oral cavity or oropharyngeal squamous cell carcinomas. A
      lingual floor-of-mouth flap was created allowing delivery of the tongue and floor
      of mouth without lip splitting, mandibulotomy, or mandibulectomy. After resection
      of the tumour and repair of the defect, the musculature of the floor of the mouth
      was reattached to the lingual cortex of the mandible using Mitek minianchors.
      There was adequate exposure in all the patients. Wound margin dehiscence occurred
      in four patients resulting in an orocervical fistula in three patients.
      Mandibular osteotomy and subsequent osteosynthesis were avoided. Thus instability
      and infection of the osteotomy site were avoided. However, additional mandibular
      osteotomy is feasible.

PMID- 11467396
TI  - Heterogeneity of proteinkinase C activity and PKC-zeta expression in clinical
      breast carcinomas.
AB  - Proteinkinase C (PKC) is involved in carcinogenesis, proliferation, and
      metastatic spread of breast cancer. New anticancer strategies have been developed
      with PKC as a potential target for therapeutic intervention. However, most of the
      encouraging preliminary data were observed in breast cancer cell lines only.
      Insignificant information is available concerning clinical breast cancer cells.
      Our aim was to investigate the involvement of PKC in clinical breast carcinoma
      cells. To this end, we set up short-term cultures (3 days) of native tumor cells
      derived from 12 patients with advanced breast cancer. Addition of commonly used
      antineoplastics, including both single agents and combinations (tamoxifen,
      Adriamycin, paclitaxel, Adriamycin plus paclitaxel, epirubicin plus 4-OOH
      cyclophosphamide, mitoxantrone, mitoxantrone plus vinorelbin, vinorelbin),
      simulated the clinical situation. In relation to each control we determined total
      PKC activity and quantified the PKC-zeta isoform. In 6 patients, no obvious
      alteration of PKC activities was detected. In the remainder, either inhibition or
      augmentation of PKC activity in the presence of cytostatics was detected.
      However, no tendency could be observed concerning the influence of the
      therapeutics on PKC activity. PKC-zeta expression was much more heterogeneous
      than activity assays. Although anticancer drugs influenced PKC-zeta expression,
      the results showed no uniformity with regard to PKC-zeta expression. Moreover,
      PKC-zeta expression did not correlate with total PKC activity, indicating a
      differential expression of different PKC isoenzymes. Therefore, we conclude that
      both PKC activity and PKC-zeta expression differ individually. More data
      concerning this topic are necessary prior to offering a clinically useful PKC
      tailored regimen.

PMID- 11467397
TI  - Soluble interleukin-2 receptor and interleukin-8 plasma levels during and after
      cardiopulmonary bypass: correlations with creatine kinase and creatine kinase MB.
AB  - In this study, soluble receptor of interleukin-2, interleukin-8, creatine kinase,
      and creatine kinase MB isoenzyme levels were determined serially before, during,
      and after cardiopulmonary bypass in blood samples of 24 patients. Interleukin-2
      receptor levels were 683+/-80 U/ml in the preoperative period and 640+/-60 U/ml
      during hypothermia. Subsequently, these levels increased significantly at the end
      of the procedure (791+/-70 U/ml, P<0.01), remaining elevated 1 h after (882+/-92
      U/ml, P<0.001) and reaching peak values 24 h postoperatively (1,752+/-200 U/ml,
      P<0.001). Preoperative plasma values of interleukin-8 were 230+/-43 pg/ml.
      Interleukin-8 concentrations were 185+/-25 pg/ml during hypothermia. The peak
      interleukin-8 levels were observed at the end of cardiopulmonary bypass (754+/-94
      pg/ml, P<0.001) and tended to decrease 1 h after the procedure (643+/-76 pg/ml,
      P<0.001), declining to preoperative values, 24 h postoperatively (273+/-41
      pg/ml). Interleukin-2 receptor levels correlated well with creatine kinase levels
      during the procedure. Furthermore, creatine kinase MB levels were correlated with
      interleukin-2 receptor values only at the end and 1 h after completion of
      cardiopulmonary bypass. We concluded that interleukin-8 and Interleukin-2
      receptor levels are elevated after cardiopulmonary bypass and may contribute to
      myocardial injury as reflected by increased levels of creatine kinase and
      creatine kinase MB and correlations between interleukin-2 receptor and both
      creatine kinase and creatine kinase MB levels.

PMID- 11467398
TI  - Reassessment of monoethylglycinexylidide as preoperative liver function test in a
      rat model of liver cirrhosis and man.
AB  - It is known that lidocaine is rapidly metabolized by the hepatic cytochrome P-450
      system to form monoethylglycinexylidide (MEGX), its primary metabolite. We
      analyzed serum MEGX levels experimentally and clinically by fluorescent
      polarization immunoassay to reassess preoperative liver microsome functions.
      EXPERIMENTAL STUDY: Liver cirrhosis was produced in rats by intra-abdominal
      injection of thioacetamide. MEGX, indocyanine green test (ICG), and liver
      biochemical variables were measured periodically. Then, survival rates were
      assessed after the rats received a 70% hepatectomy. CLINICAL STUDY: MEGX levels
      were measured in various human patients with chronic hepatitis or liver cirrhosis
      who underwent hepatectomy. Serum MEGX levels significantly dropped and ICG levels
      significantly rose with macroscopic and histologic progression of liver cirrhosis
      in rats. The MEGX levels correlated closely with albumin levels and ICG.
      Preoperative MEGX and ICG levels of the mortal group of rats differed
      significantly from those of the survival group with 70% hepatectomy. Furthermore,
      100% of the rats with MEGX levels above 40 ng/ml and ICG levels below 1.0%. In
      the clinical study, MEGX levels were significantly lower in patients with chronic
      hepatitis or liver cirrhosis than in healthy volunteers and correlated
      significantly with liver function tests such as albumin, Fischer's ratio,
      prothrombin time, hepaplastin and ICG. A significant difference was found in MEGX
      levels between patients receiving lobectomy and those receiving subsegmentectomy
      or partial hepatectomy. All patients tolerated their operations. Our data
      indicate that the MEGX test combined with ICG test and Child-Pugh classification
      is a better predictor of residual liver reserve capacity, and the analysis of
      hepatic MEGX formation might prove useful for rapid and reliable assessment liver
      function and choice of surgical treatment.

PMID- 11467399
TI  - Effect of intrahepatic omental implantation on angiogenesis in rat liver with
      hepatic artery ligation.
AB  - Despite early surgical intervention, the results of treating hepatic artery
      thrombosis remain poor. The use of omental flaps is well documented for its
      angiogenic potential in promoting neovascularization in ischemic tissues. This
      experimental study evaluated the formation of new blood-vessels after omental
      implantation (OI) in rats after ligation of the hepatic artery. Wistar rats were
      used and divided into the following groups: I OI with HAL, II OI without HAL, III
      hepatic artery ligation (HAL). For angiography, measurements were made of liver
      tissue blood flow by the laser Doppler method and of hepatic artery flow by the
      colored microsphere method (CMS), and immunohistochemical study was done for
      vascular endothelial growth factor (VEGF). The rats were killed at 1, 3, 7 or 30
      days after laparotomy. Relative arterial hepatic blood flow in the implanted lobe
      of group I, as determined by CMS, reached 50% of control values 7 days after
      surgery. Angiography and microscopic studies of the excised liver revealed
      distinct angiogenesis surrounding the omental implant in the liver for 7 days
      postoperatively. The formation of new blood-vessels after OI was not observed in
      livers without HAL. Omental implantation appears to be useful in preventing organ
      anoxia after hepatic artery thrombosis.

PMID- 11467400
TI  - The acute phase response following implantation of triclosan-bonded vascular
      prostheses.
AB  - OBJECTIVE: Infection of prosthetic material is a major complication of vascular
      surgery. Therapy for it includes implantation of antimicrobial prostheses bonded
      with different antimicrobial agents. These agents may, however, induce an acute
      phase reaction following implantation in the host, thus compromising follow-up of
      the infection. It is not known whether the antimicrobial agent triclosan induces
      a significant acute phase reaction when bonded to vascular prostheses. METHODS:
      To study this, 34 adult swine weighing 20-30 kg were allotted randomly to the
      following groups: (1) controls with untreated prostheses, (2) control group with
      triclosan-bonded prostheses, (3) therapy group with untreated prostheses, local
      infection with Staphylococcus aureus surgical revision, and exchange with new,
      untreated prostheses, and (4) therapy group with untreated prostheses, local
      infection with S. aureus, surgical revision, and exchange with triclosan-bonded
      prostheses. Serum C-reactive protein (CRP) and haptoglobin values were determined
      during the 28-day period after surgery. The study was performed at the Institute
      for Surgical Research of the Ludwig Maximilian University School of Medicine in
      Munich. RESULTS: Normal ranges of serum CRP and haptoglobin values were 10.7+/
      1.4 microg/ml and 2.5+/-0.3 mg/ml, respectively. Following implantation of
      untreated and triclosan-bonded vascular prostheses, significantly elevated serum
      CRP and haptoglobin values were observed. No significant differences between
      results with triclosan-bonded and untreated prostheses were observed in control
      or treatment groups. No correlation was found between acute phase reaction and
      the absence or presence of infection. CONCLUSIONS: Triclosan is the only
      antimicrobial agent that bonds to vascular prosthetic material without the need
      of a sealant. Our data indicate that vascular prosthesis implantation, whether
      untreated and triclosan-bonded, results in a significant acute phase reaction. No
      differences between antimicrobial and untreated prostheses were observed,
      independently of the absence or presence of infection. The antimicrobial agent
      itself did not induce a severe acute phase response and may, therefore, be used
      in patients at risk of infection.

PMID- 11467401
TI  - Evaluation of cerebral vasospasm with transcranial magnetic stimulation: an
      experimental study.
AB  - Despite the current use of several different methods for diagnosis and follow-up
      of cerebral vasospasm after subarachnoid hemorrhage, an easy, quick, reliable,
      and noninvasive method is still needed for evaluation of this entity. We
      investigated the value of transcranial magnetically evoked motor potential
      changes during the vasospasm period in a rabbit experimental subarachnoid
      hemorrhage model. We also recorded motor evoked potential changes after
      deferoxamine treatment during vasospasm. Our results reveal a significant
      increase in latency periods of evoked potentials during the angiographically
      proven vasospasm period (34.5%) over those in sham-operated rabbits (9.5%). With
      deferoxamine treatment, only a minor increase in latency periods (4.5%) was
      detected after subarachnoid hemorrhage. These results suggest the potential value
      of evoked motor potential recording as a diagnostic tool in cases of cerebral
      vasospasm.

PMID- 11467402
TI  - Ischemia/reperfusion-induced pancreatitis in rats: a new model of complete
      normothermic in situ ischemia of a pancreatic tail-segment.
AB  - Ischemia/reperfusion injury plays an important role in the development of graft
      pancreatitis and thrombosis after pancreas transplantation. Up to now there are
      few therapeutic options for this severe complication because very little is known
      about pancreatic ischemia/reperfusion injury. The same pathomechanisms may also
      be involved in the induction and determination of the course of acute
      pancreatitis. We observed the effect of 2 h of warm in situ ischemia on the
      postischemic tissue oxygenation, histological organ damage, and pancreatic
      enzymes. Experiments were performed in 21 male Wistar rats. In sham-operated
      animals without ischemia, the pancreas was not dissected. In the
      ischemia/reperfusion group a pancreatic tail-segment was carefully separated from
      the head, and ischemia was induced by clamping the splenic vessels for 2 h, after
      flushing the pancreatic tail-segment with heparinized saline. Animals treated
      similarly, but with opening of the clamps some seconds after induction of
      ischemia, served as controls. The animals were observed for 2 h after
      reperfusion. Tissue oxygenation was monitored by a PO2-sensitive probe (LICOX,
      GMS, Kiel, Germany) which was implanted into the pancreatic tissue. Blood samples
      were taken before, 5 min, 60 min, and 120 min after reperfusion. At the end of
      the experiment the pancreatic tail was excised for histological examination;
      biopsies froin the non-ischemic pancreatic head served as intraindividual control
      to exclude side effects on the nonischemic pancreatic head. In the
      ischemia/reperfusion group, PO2ti was significantly lower 1 h (18.0+/-1.7 mmHg)
      and 2 h (16.4+/-1.6 mmHg) after reperfusion compared with baseline conditions
      (32.8+/-5.2 mmHg) and the control group (1 h 30.6+/-1.9 mmHg, 2 h 32.4+/-2.4
      mmHg). Histological injury score and plasma lipase activity were significantly
      higher in the ischemia/reperfusion group compared with the control group. Thus we
      describe a new experimental model of complete normothermic in situ ischemia of a
      pancreatic tail-segment with the possibility of flushing the pancreatic tail
      segment and selective local application of drugs to the pancreas.

PMID- 11467403
TI  - The effects of pentoxifylline treatment on bacterial translocation after
      hemorrhagic shock in rats.
AB  - Bacterial translocation is thought to be responsible for infectious complications
      after hemorrhagic shock. The aim of this study was to investigate the effects of
      pentoxifylline treatment on bacterial translocation in animals subjected to
      hemorrhagic shock. Thirty-one Wistar albino rats (280-360 g) were divided into
      three groups: sham (n=10), shock (n=11), and shock-pentoxifylline (n=10). Blood
      was not withdrawn from sham rats. Shock rats were subjected to 30 min of shock
      followed by reinfusion of shed blood. Shock/pentoxifylline rats received
      pentoxifylline after reinfusion of shed blood. After hemorrhage and reinfusion
      (24 h), the mesenteric lymph nodes, liver, spleen, and blood samples were
      evaluated using quantitative microbiological techniques, and the numbers of
      colony-forming units were compared between groups. Cecum was removed to evaluate
      the bacterial population. Ileum and cecum were examined histologically. The
      incidence of bacterial translocation was higher in the shocked rats (63%) than in
      the sham shock rats (10%). Pentoxifylline reduced the incidence of shock-induced
      bacterial translocation to 0%. Cecal bacterial levels were significantly higher
      in the shock rats than in the sham and shock/pentoxifylline rats. The
      histological damage caused by hemorrhagic shock was prevented by pentoxifylline
      treatment. In conclusion, the hemorrhagic shock triggered translocation of
      bacteria to the mesenteric lymph nodes, spleen, liver, and blood of rats.
      Pentoxifylline treatment just after shed blood transfusion significantly
      attenuated this phenomenon.

PMID- 11467404
TI  - Malondialdehyde level and total superoxide dismutase activity in seminal fluid
      from patients with varicocele.

PMID- 11467405
TI  - Establishment of reference values for the PFA-100 platelet function analyzer in
      pediatrics.

PMID- 11467406
TI  - Oxidative stress and endothelial damage in patients with asymptomatic carotid
      atherosclerosis.
AB  - It is known that oxidative stress can be able to induce cytotoxicity of blood
      cells, stimulate release of inflammatory cytokines, and induce the production of
      growth factors. The aim of this study was to investigate oxidative stress and
      endothelial dysfunction in patients with asymptomatic carotid artery disease and
      healthy controls. Native low-density lipoproteins, oxidised low-density
      lipoproteins, malondialdehyde, nitrates, glutathione peroxidase activity and
      endothelin-1 were determined in patients without severe (range between 30% and
      50%) carotid artery stenosis. Native low-density lipoproteins, oxidized low
      density lipoproteins, malondialdehyde, glutathione peroxydase, and endothelin-1
      concentrations were higher in patients than in health controls (P<0.001). No
      difference was observed in nitrate values (P<0.8). Our results revealed oxidative
      stress in patients without severe carotid artery stenosis and clinical symptoms.
      This was shown by the elevated malondialdehyde and oxidized low-density
      lipoprotein levels.

PMID- 11467407
TI  - Tissue culture of isolated human pancreatic islets infected with different
      strains of coxsackievirus B4: assessment of virus replication and effects on
      islet morphology and insulin release.
AB  - The aim was to study whether different strains of Coxsackievirus B4 (CBV-4) are
      able to infect human pancreatic islet cells in vitro and cause morphological and
      functional damages. Isolated islets maintained in tissue culture were infected
      with five well- characterised strains of CBV-4. Aliquots of the culture medium
      were analysed with regard to virus replication and insulin content. Infected and
      uninfected islets were examined by light microscopy to determine the degree of
      virus-induced cytopathic effect (CPE). The results showed that the islet cells
      were susceptible to infection by all the strains of CBV-4 although the outcome of
      the infection differed. The virus titres obtained at 48 and 72 hours post
      infection differed significantly between all the CBV-4 strains (p<0.001),
      indicating different ability to replicate in islet cells. Pronounced to weak CPE,
      which was partly due to the origin (donor) of the islets, was induced by four of
      the five CBV-4 strains. One strain (VD2921) replicated without causing CPE
      despite high virus titres. One (V89-4557) of the CBV-4 strains always revealed
      pronounced CPE. Infection by this strain also caused functional impairment that
      significantly affected insulin response to high glucose at 48 hours post
      infection (p<0.001). Replication of another CBV-4 strain (JVB) in the islet cells
      significantly increased the release of insulin compared to non-infected control
      cells (p<0.001) indicating damage of the beta-cells leading to leakage of
      insulin.

PMID- 11467408
TI  - Characterization of obesity phenotypes in Psammomys obesus (Israeli sand rats).
AB  - Psammomys obesus (the Israeli sand rat) has been well studied as an animal model
      of Type 2 diabetes. However, obesity phenotypes in these animals have not been
      fully characterized. We analyzed phenotypic data including body weight,
      percentage body fat, blood glucose and plasma insulin concentration for over 600
      animals from the Psammomys obesus colony at Deakin University to investigate the
      relationships between body fat, body weight and Type 2 diabetes using regression
      analysis and general linear modelling. The body weight distribution in Psammomys
      obesus approximates a normal distribution and closely resembles that observed in
      human populations. Animals above the 75th percentile for body weight had
      increased body fat content and a greater risk of developing diabetes. Increased
      visceral fat content was also associated with elevated blood glucose and plasma
      insulin concentrations in these animals. A familial effect was also demonstrated
      in Psammomys obesus, and accounted for 51% of the variation in body weight, and
      23-26% of the variation in blood glucose and plasma insulin concentrations in
      these animals. Psammomys obesus represents an excellent animal model of obesity
      and Type 2 diabetes that exhibits a phenotypic pattern closely resembling that
      observed in human population studies. The obesity described in these animals was
      familial in nature and was significantly associated with Type 2 diabetes.

PMID- 11467409
TI  - Correlation between pancreatic islet uncoupling protein-2 (UCP2) mRNA
      concentration and insulin status in rats.
AB  - Hypothesizing that UCP2 may influence insulin secretion by modifying the ATP/ADP
      ratio within pancreatic islets, we have investigated the expression of intraislet
      UCP2 gene in rats showing insulin oversecretion (non-diabetic Zucker fa/fa obese
      rats, glucose-infused Wistar rats) or insulin undersecretion (fasting and mildly
      diabetic rats). We found that in Zucker fa/fa obese rats, hyperinsulinemia
      (1222+/-98 pmol/l vs. 128+/-22 pmol/l in lean Zucker rats) was accompanied by a
      significant increase in UCP2 mRNA levels. In rat submitted to a 5 day infusion
      with glucose, hyperinsulinemia (1126+/-101 pmol/l vs. 215+/-25 pmol/l in Wistar
      control rats), coincided with an enhanced intraislet UCP2 gene expression,
      whereas a 8h or a 2 day-infusion did not induce significant changes in UCP2 mRNA
      expression. In rats made hypoinsulinemic and mildly diabetic by the injection of
      a low dose of streptozotocin, and in 4-day-fasting rats (plasma insulin 28+/-5
      pmol/l) UCP2 gene expression was sharply decreased. A 3-day-fast was ineffective.
      The data show the existence of a time-dependent correlation between islet mRNA
      UCP2 and insulin that may be interpreted as an adaptative response to prolonged
      insulin excess.

PMID- 11467410
TI  - A thiazolidinedione improves in vivo insulin action on skeletal muscle glycogen
      synthase in insulin-resistant monkeys.
AB  - Thiazolidinediones (TZD) have been shown to have anti-diabetic effects including
      the ability to decrease fasting hyperglycemia and hyperinsulinemia, increase
      insulin-mediated glucose disposal rate (M) and decrease hepatic glucose
      production, but the mechanisms of action are not well established. To determine
      whether a TZD (R-102380, Sankyo Company Ltd., Tokyo, Japan) could improve insulin
      action on skeletal muscle glycogen synthase (GS), the rate-limiting enzyme in
      glycogen synthesis, 4 insulin-resistant obese monkeys were given 1 mg/kg/day R
      102380 p.o. for a 6-week period. Skeletal muscle GS activity and glucose 6
      phosphate (G6P) content were compared between pre-dosing and dosing periods
      before and during the maximal insulin-stimulation of a euglycemic
      hyperinsulinemic clamp. Compared to pre-dosing, insulin-stimulated GS activity
      and G6P content were increased by this TZD: GS independent activity (p = 0.02),
      GS total activity (p = 0.005), GS fractional activity (p = 0.06) and G6P content
      (p = 0.02). The change in GS activity induced by in vivo insulin (insulin
      stimulated minus basal) was also increased by this TZD: GS independent activity
      (p = 0.03) and GS fractional activity (p = 0.04). We conclude that the TZD R
      102380 improves insulin action at the skeletal muscle in part by increasing the
      activity of glycogen synthase. This improvement in insulin sensitivity may be a
      key factor in the anti-diabetic effect of the thiazolidinedione class of agents.

PMID- 11467411
TI  - The relationship between cholesterol absorption and intestinal cholesterol
      synthesis in the diabetic rat model.
AB  - The chylomicron remnant particle is thought to be particularly atherogenic and we
      have previously shown alterations in post-prandial lipoproteins which could
      contribute to their atherogenicity. Cholesterol metabolism is disturbed in
      diabetes, yet the effect of diabetes on intestinal cholesterol synthesis and
      absorption has rarely been investigated. The aim of this study was to examine
      cholesterol absorption and intestinal synthesis of cholesterol in the
      streptozotocin diabetic rat. Twelve diabetic rats were paired with 12 control
      rats. [14C]-Cholesterol emulsion was administered and the lymph duct was
      canulated. Lymph was collected for 4h. At sacrifice blood was taken for plasma
      lipoprotein measurements. Chylomicrons were prepared from the lymph by
      ultracentrifugation and [14C]-cholesterol content was determined by liquid
      scintillation counting. Lymph apolipoprotein B48 was isolated by gradient gel
      electrophoresis, and quantified by densitometric scanning. Serum triglyceride and
      cholesterol were greatly elevated in diabetic compared to control animals (260+/
      90 and 9.8+/-8.0 mg/ml vs. 1.0+/-0.4 and 0.6+/-0.3 mg/ml, p < 0.0001
      respectively). Lymph chylomicron apo B48 was similar in the two groups.
      Cholesterol absorption was not significantly different in diabetic compared to
      control rats but cholesterol synthesis was significantly higher in the diabetic
      animals (550+/-352 vs. 322+/-113 microg/h p < 0.03). There was a positive
      correlation between apo B48 and cholesterol absorption (r = 0.70, p < 0.01) in
      the diabetic rats and control rats (r = 0.71, p < 0.01) but no correlation
      between apo B48 and cholesterol synthesis in either group. This study
      demonstrates that cholesterol synthesis was increased in diabetes whereas
      cholesterol absorption was unaffected suggesting that intestinal cholesterol
      synthesis made an important contribution to the hypercholesterolaemia seen in the
      diabetic animals.

PMID- 11467412
TI  - Streptozotocin and alloxan-based selection improves toxin resistance of insulin
      producing RINm cells.
AB  - The aim of our study was to develop a method for selection of subpopulations of
      insulin producing RINm cells with higher resistance to beta cell toxins. Cells,
      resistant to streptozotocin (RINmS) and alloxan (RINmA), were obtained by
      repeated exposure of parental RINm cells to these two toxins, while the defense
      capacity was estimated by the MTT colorimetric method, and [3H]-thymidine
      incorporation assay. We found that RINmS and RINmA displayed higher resistance to
      both streptozotocin (STZ) and alloxan (AL) when compared to the parental RINm
      cells. In contrast, no differences in sensitivity to hydrogen peroxide were found
      between toxin selected and parental cells. Partial protection from the toxic
      effect of STZ and AL was obtained only in the parental RINm cells after
      preincubation of cells with the unmetabolizable 3-O-methyl-glucose. The
      possibility that GLUT-2 is involved in cell sensitivity to toxins was confirmed
      by Western blot analysis, which showed higher expression of GLUT-2 in parental
      RINm compared to RINmS and RINmA cells. In addition to the higher cell defense
      property evidenced in the selected cells, we also found higher insulin content
      and insulin secretion in both RINmS and RINmA cells when compared to the parental
      RINm cells. In conclusion, STZ and AL treatment can be used for selection of cell
      sub-populations with higher cell defense properties and hormone production. The
      different GLUT-2 expression in parental and resistant cells suggest involvement
      of GLUT-2 in mechanisms of cell response to different toxins.

PMID- 11467413
TI  - Alterations in nitric oxide activity and sensitivity in early streptozotocin
      induced diabetes depend on arteriolar size.
AB  - Changes in NO activity may play an important role in the early increase in
      microvascular flow that has been implicated in the pathogenesis of diabetic
      microangiopathy. We assessed, in the in situ spinotrapezius muscle preparation of
      6 weeks' streptozotocin-diabetic rats (n = 6) and of age-matched controls (n =
      8), basal inside diameters of A2-A4 arterioles and the reactivity to topically
      applied acetylcholine and nitroprusside, before and after N(G)-nitro-L-arginine.
      In diabetic rats, cholinergic vasodilatation in A2-A4 arterioles was intact.
      Basal diameter in A3 and A4 arterioles was significantly higher in streptozotocin
      diabetic rats. The increased basal diameter in A3 arterioles was partially due to
      an increased contribution of NO to basal diameter. The response to nitroprusside
      was impaired in streptozotocin-diabetic rats in A2, but not in A3 and A4
      arterioles. Thus, this study shows that NO activity and sensitivity are altered
      after 6 weeks of streptozotocin-induced diabetes. These streptozotocin-induced
      changes are anatomically specific and, for arterioles, depend on their position
      within the vascular tree.

PMID- 11467414
TI  - Therapeutic differentiation of tumor-derived insulin-producing cells selected for
      resistance to diabetogenic drugs.
AB  - Differentiation therapy has been proposed as a new approach to selectively engage
      the process of tumor cell differentiation during chemotherapy of cancer. Our
      recent in vitro study suggests that such an approach can be extended and utilized
      for the selection of tumor-derived insulin-producing cells for transplantation.
      Repeated treatment with streptozotocin selected toxin resistant subpopulation of
      insulin producing tumor RINmS cells, characterized by increased level of insulin
      content and secretion. In the present study RINmS cells were found to have higher
      glucose sensitivity and insulin response compared with parental RINm cells. In
      addition, compounds known to induce elevated level of cAMP in beta-cells, such as
      isobutyl methyl xanthine, and forskolin, potentiated glucose-induced insulin
      secretion of RINmS, but had no effect on the naive parental RINm cells. These
      experiments suggest that differentiation therapy can be utilized for engineering
      insulin producing cells with improved defense and secretory mechanisms.

PMID- 11467415
TI  - Lack of expression of Gp-130 makes pancreatic beta cell lines unresponsive to the
      IL-6 family of cytokines.
AB  - Cytokine receptors from the IL-6 receptor family are comprised of ligand specific
      alpha chains and a common signalling chain, gp-130, which is also required for
      high affinity binding. A cDNA library generated from the beta-TC3 SV40 T-antigen
      transformed insulinoma cell line was screened for members of this receptor family
      potentially relevant to both beta cell development and autoimmunity. Degenerate
      oligonucleotide primers to a consensus region of these receptors were used and
      the IL-11 receptor alpha chain was identified. Despite confirmation of IL-11
      receptor mRNA expression, iodinated bioactive IL-11 did not bind specifically to
      beta-TC3 cells and gp-130-dependent cytokines did not elicit signalling events in
      beta cell lines. This was explained by absence of gp-130 protein or mRNA in the
      beta cell lines tested and in primary islets. We conclude from these results that
      the previously recognised effects of IL-6 family member cytokines on pancreatic
      islets must be indirect via other non-beta cells within the islet, rather than
      due to direct effects on beta cells themselves.

PMID- 11467416
TI  - Genetic mapping and functional studies of a natural inhibitor of the insulin
      receptor tyrosine kinase: the mouse ortholog of human alpha2-HS glycoprotein.
AB  - Fetuin/alpha2-HS glycoprotein (alpha2-HSG) homologs have been identified in
      several species including rat, sheep, pig, rabbit, guinea pig, cattle, mouse and
      human. Multiple physiological roles for these homologs have been suggested,
      including ability to bind to hydroxyapatite crystals and to specifically inhibit
      the tyrosine kinase (TK) activity of the insulin receptor (IR). In this study we
      report the identification, cloning, and characterization of the mouse Ahsg gene
      and its function as an IR-TK inhibitor. Genomic clones derived from a mouse Svj
      129 genomic library were sequenced in order to characterize the intron-exon
      organization of the mouse Ahsg gene, including an 875 bp subclone containing 154
      bp upstream from the transcription start site, the first exon, and part of the
      first intron. A second genomic subclone harboring a 3.45 kb Bgl II fragment
      contained exons 2, 3 and 4 in addition to two adjacent elements within the first
      intron-a repetitive element of the B1 family (92 bp) and a 271 bp tract of
      (T,C)n*(A,G)n. We have mapped mouse Ahsg at 16 cM adjacent to the Diacylglycerol
      kinase 3 (Dagk3) gene on chromosome 16 by genotyping interspecific backcross
      panels between C57BL/6J and Mus spretus. The position is syntenic with human
      chromosome 3q27, where the human AHSG gene resides. Using recombinant mouse
      alpha2-HSG expressed from a recombinant baculovirus, we demonstrate that mouse
      alpha2-HSG inhibits insulin-stimulated IR autophosphorylation and IR-TKA in
      vitro. In addition, mouse alpha2-HSG (25 microg/ml) completely abolishes insulin
      induced DNA synthesis in H-35 rat hepatoma cells. Based on the sequence data and
      functional analysis, we conclude that the mouse Ahsg gene is the true ortholog of
      the human AHSG gene.

PMID- 11467417
TI  - Modulation of beta-cell ouabain-sensitive 86Rb+ influx (Na+/K+ pump) by D
      glucose, glibenclamide or diazoxide.
AB  - The activity of the beta-cell Na+/K+ pump was studied by using ouabain-sensitive
      (1mM ouabain) 86Rb+ influx in beta-cell-rich islets of Umea-ob/ob mice as an
      indicator of the pump function. The present results show that the stimulatory
      effect of glucose on ouabain-sensitive 86Rb+ influx reached its approximate
      maximum at 5mM glucose. Pre-treatment of the islets with 20mM glucose for 60 min
      strongly reduced the glucose-induced stimulation of the Na+/K+ pump. Pre
      treatment (60 or 180 min) of islets at 0 mM glucose, on the other hand, did not
      affect the magnitude of the glucose-induced stimulation of 86Rb+ influx during
      the subsequent 5-min incubation. Glibenclamide stimulated the ouabain-sensitive
      86Rb+ uptake in the same manner as glucose. The stimulatory effect showed its
      apparent maximum at 0.5 microM. Pre-treatment (60 min) of islets with 1 microM
      glibenclamide did not reduce the subsequent stimulation of the ouabain-sensitive
      86Rb+ influx. The stimulatory effect of glibenclamide and D-glucose were not
      additive, suggesting that they may have the same mechanism of action. No direct
      effect of glibenclamide (0.01-1 microM) was observed on the Na+/K+ ATPase
      activity in homogenates of islets. Diazoxide (0.4mM) inhibited the Na+/K+ pump.
      This effect was sustained even after 60 min of pre-treatment of islets with 0.4mM
      diazoxide. The stimulatory effect of glibenclamide and D-glucose were abolished
      by diazoxide. It is concluded that nutrient as well as non-nutrient insulin
      secretagogues activate the Na+/K+ pump, probably as part of the membrane
      repolarisation process.

PMID- 11467418
TI  - Evidence for mechanistic alterations of Ca2+ homeostasis in Type 2 diabetes
      mellitus.
AB  - Altered cytosolic Ca2+ is implicated in the aetiology of many diseases including
      diabetes but there are few studies on the mechanism(s) of the altered Ca2+
      regulation. Using human lymphocytes, we studied cytosolic calcium (Cai) and
      various Ca2+ transport mechanisms in subjects with Type 2 diabetes mellitus and
      control subjects. Ca2+-specific fluorescent probes (Fura-2 and Fluo-3) were used
      to monitor the Ca2+ signals. Thapsigargin, a potent and specific inhibitor of the
      sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), was used to study Ca2+-store
      dependent Ca2+ fluxes. Significant (P<0.05) elevation of basal Ca, levels was
      observed in lymphocytes from diabetic subjects. Cai levels were positively
      correlated with fasting plasma glucose and HbA1c. There was also a significant
      (P<0.05) reduction in plasma membrane calcium (PMCA) ATPase activity in diabetic
      subjects compared to controls. Cells from Type 2 diabetics exhibited an increased
      Ca2+ influx (as measured both by Fluo-3 fluorescence and 45Ca assays) as a
      consequence of thapsigargin-mediated Ca2+ store depletion. Upon addition of Mn2+
      (a surrogate of Ca2+), the fura-2 fluorescence decayed in an exponential fashion
      and the rate and extent of this decline was steeper and greater in cells from
      type 2 diabetic patients. There was also a significant (P<0.05) difference in the
      Na+/Ca2+ exchange activity in Type 2 diabetic patients, both under resting
      conditions and after challenging the cells with thapsigargin, when the internal
      store Ca2+ sequestration was circumvented. Pharmacological activation of protein
      kinase C (PKC) in cells from patients resulted in only partial inhibition of Ca2+
      entry. We conclude that cellular Ca2+ accumulation in cells from Type 2 diabetes
      results from (a) reduction in PMCA ATPase activity, (b) modulation of Na+/Ca2+
      exchange and (3) increased Ca2+ influx across the plasma membrane.

PMID- 11467419
TI  - Defective morphogenesis and functional maturation in fetal islet-like cell
      clusters from OLETF rat, a model of NIDDM.
AB  - A failure in the compensate proliferation of pancreatic beta-cells, as the
      primary pathogenic event, has been reported in OLETF rat, a model of NIDDM. The
      aim of the present study is to define whether the beta-cell defect is attributed
      to the fetal stage islet development, if so, whether the defect involves down
      regulation of PDX-1 protein expression. Morphological changes, beta-cell
      function, and the expression of PDX-1 protein were examined in the cultured fetal
      islet-like cell clusters (ICCs) from OLETF rats along with their diabetes
      resistant control counterpart LETO rats in the presence of 5.5 or 11.1mM glucose
      for 48, 72, 96, and 120-hr, respectively. We have observed four abnormalities in
      the ICCs of OLETF rats. First, a defective morphogenesis was noted during the 72
      to 120-hr ICC culture, a period characterized by a dramatic increase in both beta
      cell and non-beta-cell (alpha, delta, and PP) populations in control rats. This
      defective morphogenesis was demonstrated by a growth retardation of epithelial
      stratification and poor development of both beta-cell and non-beta-cell masses
      along with a parallel decline in relevant islet hormone contents. Second, a
      functional defect was characterized by failure to response to glucose during the
      96 to 120-hr-cultured ICCs. Third, the ultrastructural analysis revealed a
      significant reduction in the number of secretory granules. Four, Western blot
      analysis showed a significant decrease of PDX-1 protein expression in the OLETF
      ICCs cultured in 11.1mM glucose for 48 to 72-hr and in 5.5mM glucose for 120-hr.
      Therefore, we concluded that during the fetal stage of islet development, OLETF
      rats exhibit both morphological and functional defects.

PMID- 11467420
TI  - Prevention of cyclophosphamide-induced accelerated diabetes in the NOD mouse by
      nicotinamide or a soy protein-based infant formula.
AB  - Spontaneous diabetes in the NOD mouse can be prevented by nicotinamide or by an
      infant formula diet in which the protein source is replaced with casein
      hydrolysate (Pregestimil) or soy protein (Prosobee). NOD mice maintained on the
      standard diet (chow and water) and given cyclophosphamide (Cy) at day 95 develop
      accelerated and synchronised diabetes within 14 days. Here, we compared the
      ability of oral nicotinamide or Prosobee, either given alone or concurrently,
      from weaning, in preventing diabetes in the Cy model. The resulting insulitis and
      the expression of intra-islet inducible nitric oxide synthase (iNOS) were
      examined at days 0, 4, 7, 11 and 14 following Cy administration. Intra-islet CD4
      and CD8 cells and macrophages were also enumerated at day 11. In mice given the
      standard diet and injected with Cy at day 95 (group 5), diabetes developed in
      7/11 mice, 14 days later. Mice exposed to oral nicotinamide (group 2), Prosobee
      (group 3) or both (group 4), did not develop the disease during this period and
      until a further 30 days (p = 0.03). In mice exposed to the standard diet and
      without Cy treatment (group 1) the insulitis scores increased slowly until day 11
      and then declined slightly at day 14 whereas mice exposed to the same diet but
      given Cy at day 95, showed a sharp decline at day 4 followed by a rapid increase
      between day 7-14. However, in mice given either nicotinamide, Prosobee or both,
      the insulitis scores at most time-points were generally lower than in Cy-treated
      animals on the standard diet. In the latter group, CD4 and CD8 cells and
      macrophages were also higher at day 11 than all other 4 groups (CD4: p < 0.05;
      CD8: p< 0.05; macrophages: p<0.0001). The number of iNOS labelled cells increased
      progressively in mice on the standard diet and given Cy and were significantly
      higher at days 4, 7 and 11 than in the 3 dietary groups. Thus, oral nicotinamide
      or Prosobee, either alone or together, prevents Cy induced diabetes in the NOD
      mouse. The protective diets suppress Cy-induced intra-islet immune cell influx
      and iNOS expression.

PMID- 11467421
TI  - Species-specific bird functions in a forest-canopy food web.
AB  - Bird functions in a forest-canopy food web were evaluated by a large-scale field
      experiment using 'canopy' enclosures. By controlling the presence of two bird
      species, great tits (Parus major; foliage gleaner) and nuthatches (Sitta
      europaea; trunk gleaner), in the enclosures, their effect on predatory insects
      (ants), herbivorous insects (Lepidoptera larvae) and producers (oak trees) was
      quantified. Great tits reduced the density of Lepidoptera larvae and, indirectly,
      leaf damage, but had no impact on ants. Nuthatches decreased the density of ants
      but did not influence either Lepidoptera larvae or leaf damage. These results
      highlight species-specific functions of birds in the maintenance of forest
      ecosystems.

PMID- 11467422
TI  - Invasion speeds in fluctuating environments.
AB  - Biological invasions are increasingly frequent and have dramatic ecological and
      economic consequences. A key to coping with invasive species is our ability to
      predict their rates of spread. Traditional models of biological invasions assume
      that the environment is temporally constant. We examine the consequences for
      invasion speed of periodic and stochastic fluctuations in population growth rates
      and in dispersal distributions.

PMID- 11467423
TI  - Testing for predator dependence in predator-prey dynamics: a non-parametric
      approach.
AB  - The functional response is a key element in all predator-prey interactions.
      Although functional responses are traditionally modelled as being a function of
      prey density only, evidence is accumulating that predator density also has an
      important effect. However, much of the evidence comes from artificial
      experimental arenas under conditions not necessarily representative of the
      natural system, and neglecting the temporal dynamics of the organism (in
      particular the effects of prey depletion on the estimated functional response).
      Here we present a method that removes these limitations by reconstructing the
      functional response non-parametrically from predator-prey time-series data. This
      method is applied to data on a protozoan predator-prey interaction, and we obtain
      significant evidence of predator dependence in the functional response. A crucial
      element in this analysis is to include time-lags in the prey and predator
      reproduction rates, and we show that these delays improve the fit of the model
      significantly. Finally, we compare the non-parametrically reconstructed
      functional response to parametric forms, and suggest that a modified version of
      the Hassell-Varley predator interference model provides a simple and flexible
      function for theoretical investigation and applied modelling.

PMID- 11467424
TI  - Nonlinearity in the predation risk of prey mobility.
AB  - Odorous waste products such as urine and faeces are unavoidable for most animals
      and are widely exploited by predators and their prey. Consequently, waste
      accumulations can be risky and prey which increase their mobility in order to
      disperse and dilute their waste should avoid a high predation risk until this
      benefit is balanced by the increasing risks of random predator encounter. This
      hypothesis was tested for voles (Microtus spp.) in Finland which are vulnerable
      to predation due to the scent and ultraviolet attractiveness of their urine. The
      mortality and mobility of radio-collared voles showed a U-shaped relationship,
      regardless of vole sex, species or population cycle phase. The low risks for prey
      making intermediate movements suggest that predation risk can exert strong
      selective pressures on prey such that they have little respite from the risk of
      being killed.

PMID- 11467425
TI  - Moth hearing in response to bat echolocation calls manipulated independently in
      time and frequency.
AB  - We measured the auditory responses of the noctuid moth Noctua pronuba to bat
      echolocation calls which were manipulated independently in time and frequency.
      Such manipulations are important in understanding how insect hearing influences
      the evolution of echolocation call characteristics. We manipulated the calls of
      three bat species (Rhinolophus hipposideros, Myotis nattereri and Pipistrellus
      pipistrellus) that use different echolocation call features by doubling their
      duration or reducing their frequency, and measured the auditory thresholds from
      the A1 cells of the moths. Knowing the auditory responses of the moth we tested
      three predictions. (i) The ranking of the audibility of unmanipulated calls to
      the moths should be predictable from their temporal and/or frequency structure.
      This was supported. (ii) Doubling the duration of the calls should increase their
      audibility by ca. 3 dB for all species. Their audibility did indeed increase by
      2.1-3.5 dB. (iii) Reducing the frequency of the calls would increase their
      audibility for all species. Reducing the frequency had small effects for the two
      bat species which used short duration (2.7-3.6 ms) calls. However, the relatively
      long-duration (50 ms), largely constant-frequency calls of R. hipposideros
      increased in audibility by 21.6 dB when their frequency was halved. Time and
      frequency changes influence the audibility of calls to tympanate moths in
      different ways according to call design. Large changes in frequency and time had
      relatively small changes on the audibility of calls for short, largely broadband
      calls. Channelling energy into the second harmonic of the call substantially
      decreased the audibility of calls for bats which use long-duration, constant
      frequency components in echolocation calls. We discuss our findings in the
      contexts of the evolution of both bat echolocation call design and the potential
      responses of insects which hear ultrasound.

PMID- 11467426
TI  - History influences signal recognition: neural network models of tungara frogs.
AB  - Animals often attend to only a few of the cues provided by the complex displays
      of conspecifics. We suggest that these perceptual biases are influenced by
      mechanisms of signal recognition inherited from antecedent species. We tested
      this hypothesis by manipulating the evolutionary history of artificial neural
      networks, observing how the resulting networks respond to many novel stimuli and
      comparing these responses to the behaviour of females in phonotaxis experiments.
      Networks with different evolutionary histories proved equally capable of evolving
      to recognize the call of the tungara frog, Physalaemus pustulosus, but exhibited
      distinct responses to novel stimuli. History influenced the ability of networks
      to predict known responses of tungara frogs; network accuracy was determined by
      how closely the network history approximated the hypothesized history of the
      tungara frog. Our findings emphasize the influence of past selection pressures on
      current perceptual mechanisms, and demonstrate how neural network models can be
      used to address behavioural questions that are intractable through traditional
      methods.

PMID- 11467427
TI  - Maternal grandmothers improve nutritional status and survival of children in
      rural Gambia.
AB  - Hypotheses for the evolution of human female life-history characteristics have
      often focused on the social nature of human societies, which allows women to
      share the burden of childcare and provisioning amongst other members of their kin
      group. We test the hypothesis that child health and survival probabilities will
      be improved by the presence of kin using a longitudinal database from rural
      Gambia. We find that the only kin to improve the nutritional status of children
      significantly (apart from mothers) are maternal grandmothers, and that this is
      reflected in higher survival probabilities for children with living maternal
      grandmothers. There is also evidence that the reproductive status of the maternal
      grandmother influences child nutrition, with young children being taller in the
      presence of non-reproductive grandmothers than grandmothers who are still
      reproductively active. Paternal grandmothers and male kin, including fathers,
      have negligible impacts on the nutritional status and survival of children.

PMID- 11467428
TI  - Reinforcement and divergence under assortative mating.
AB  - Traits that cause assortative mating such as the flowering time in plants and
      body size in animals can produce reproductive isolation between hybridizing
      populations. Can selection against unfit hybrids cause two populations to diverge
      in their mean values for these kinds of traits? Here I present a haploid
      analytical model of one population that receives gene flow from another. The
      partial pre-zygotic isolation between the two populations is caused by
      assortative mating for a trait that is influenced by any number of genes with
      additive effects. The post-zygotic isolation is caused by selection against
      genetic incompatibilities that can involve any form of selection on individual
      genes and gene combinations (epistasis). The analysis assumes that the
      introgression rate and selection coefficients are small. The results show that
      the assortment trait mean will not diverge from the immigrants unless there is
      direct selection on the trait favouring it to do so or there are genes of very
      large effect. The amount of divergence at equilibrium is determined by a balance
      between direct selection on the assortment trait and introgression from the other
      population. Additional selection against hybrid genetic incompatibilities reduces
      the effective migration rate and allows greater divergence. The role of
      assortment in speciation is discussed in the light of these results.

PMID- 11467429
TI  - Inbreeding depression influences lifetime breeding success in a wild population
      of red deer (Cervus elaphus).
AB  - Evolutionary and conservation biologists have a long-standing interest in the
      consequences of inbreeding. It is generally recognized that inbred individuals
      may experience reduced fitness or inbreeding depression. By the same token,
      relatively outbred individuals can have greater than average fitness, i.e.
      heterosis. However, nearly all of the empirical evidence for inbreeding
      depression comes from laboratory or domestic species. Inbreeding depression and
      heterosis are difficult to detect in natural populations due to the difficulties
      in establishing pedigrees. An alternative method is to correlate heterozygosity,
      which is measured using genetic markers, with a trait related to fitness. The
      typically studied traits, such as juvenile survival and growth rates, either
      cover only early life or are weakly correlated with lifetime breeding success
      (LBS). In this paper we show that heterozygosity is positively associated with
      male and female adult LBS in a wild population of red deer (Cervus elaphus) on
      the Isle of Rum, Scotland. To the authors' knowledge, this is the first time that
      inbreeding depression and/or heterosis have been detected for a trait highly
      correlated with overall fitness in both sexes in a wild population.

PMID- 11467430
TI  - Genetics of resistance against defences of the host plant Barbarea vulgaris in a
      Danish flea beetle population.
AB  - One essential aspect of the study of the evolution of host-plant use by insects
      is (variation in) its genetic basis. The genetic basis of the ability of a flea
      beetle (Phyllotreta nemorum) to use the crucifer Barbarea vulgaris ssp. arcuata
      (G type) as a host plant was studied in a Danish population (Kvaerkeby) occurring
      naturally on this atypical host plant. Evidence was found that this ability was
      determined by a single, major, autosomal gene, although the presence of genes at
      additional loci at lower frequencies could not be excluded. No evidence was found
      for sex-linked inheritance, which was common in a second population in Denmark
      (Ejby) using Barbarea as a host plant. All beetles in the Kvaerkeby sample were
      homozygous 'resistant' to Barbarea defence. After crossing resistant F1 offspring
      from pairs consisting of a field-collected beetle and a susceptible one amongst
      each other, genotyping the F2 (reared on radish) showed a 1:2:1 ratio of
      homozygous resistant, heterozygous and susceptible beetles. No evidence was found
      for a reduction in the viability of beetles that were homozygous resistant at the
      autosomal locus, in contrast to what had been found earlier for two backcrossed
      lines founded by beetles from Ejby. The results show that there is variation in
      the genetic basis of host-plant use across local populations and imply that
      population structure should form part of the study of the interaction between P.
      nemorum and its host plants.

PMID- 11467431
TI  - Adaptive dynamics in diploid, sexual populations and the evolution of
      reproductive isolation.
AB  - Evolutionary branching is the process whereby an initially monomorphic population
      evolves to a point where it undergoes disruptive selection and splits up into two
      phenotypically diverging lineages. We studied evolutionary branching in three
      models that are ecologically identical but that have different genetic systems.
      The first model is clonal, the second is sexual diploid with additive genetics on
      a single locus and the third is like the second but with an additional locus for
      mate choice. Evolutionary branching occurred under exactly the same ecological
      circumstances in all three models. After branching the evolutionary dynamics may
      be qualitatively different. In particular, in the diploid, sexual models there
      can be multiple evolutionary outcomes whereas in the corresponding clonal model
      there is only one. We showed that evolutionary branching favours the evolution of
      (partial) assortative mating and that this in turn effectively restores the
      results from the clonal model by rendering the alternative outcomes unreachable
      except for the one that also occurs in the clonal model. The evolution of
      assortative mating during evolutionary branching can be interpreted as the
      initial phase of sympatric speciation with phenotypic divergence and partial
      reproductive isolation.

PMID- 11467432
TI  - The monophyletic origin of freshwater crayfish estimated from nuclear and
      mitochondrial DNA sequences.
AB  - Despite their widespread use as model organisms, the phylogenetic status of the
      around 520 species of freshwater crayfish is still in doubt. One hypothesis
      suggests two distinct origins of freshwater crayfish as indicated by their
      geographical distribution, with two centres of origin near the two present
      centres of diversity; one in south-eastern United States and the other in
      Victoria, Australia. An alternative theory proposes a single (monophyletic)
      origin of freshwater crayfish. Here we use over 3000 nucleotides from three
      different gene regions in estimating phylogenetic relationships among freshwater
      crayfish and related Crustacea. We show clear evidence for monophyly of
      freshwater crayfish and for the sister-group relationship between crayfish and
      clawed lobsters. Monophyly of the superfamilies Astacoidea and Parastacoidea is
      also supported. However, the monophyly of the family Cambaridae is questioned
      with the genus Cambaroides being associated with the Astacidae.

PMID- 11467433
TI  - Origin, radiation, dispersion and allopatric hybridization in the chub Leuciscus
      cephalus.
AB  - The phylogenetic relationships of 492 chub (Leuciscus cephalus) belonging to 89
      populations across the species' range were assessed using 600 base pairs of
      cytochrome b. Furthermore, nine species belonging to the L. cephalus complex were
      also analysed (over the whole cytochrome b) in order to test potential allopatric
      hybridization with L. cephalus sensu stricto (i.e. the chub). Our results show
      that the chub includes four highly divergent lineages descending from a quick
      radiation that took place three million years ago. The geographical distribution
      of these lineages and results of the nested clade analysis indicated that the
      chub may have originated from Mesopotamia. Chub radiation probably occurred
      during an important vicariant event such as the isolation of numerous Turkish
      river systems, a consequence of the uplift of the Anatolian Plateau (formerly
      covered by a broad inland lake). Dispersion of these lineages arose from the
      changes in the European hydrographic network and, thus, the chub and endemic
      species of the L. cephalus complex met by secondary contacts. Our results show
      several patterns of introgression, from Leuciscus lepidus fully introgressed by
      chub mitochondrial DNA to Leuciscus borysthenicus where no introgression at all
      was detected. We assume that these hybridization events might constitute an
      important evolutionary process for the settlement of the chub in new environments
      in the Mediterranean area.

PMID- 11467434
TI  - The one that did not get away: individual assignment using microsatellite data
      detects a case of fishing competition fraud.
AB  - Assignment of an individual to the population from which it most probably
      originated based on its multilocus genotype has been widely applied in recent
      years. In this study, individual assignment based on microsatellite data was used
      to identify a case of fishing competition fraud. Despite the fact that the true
      population of origin was most probably not among the reference populations,
      recent modifications of the assignment tests were used in confidently excluding
      (p < 0.0001) the possibility of a 5.5 kg salmon (Salmo salar) originating from
      the fishing competition location, Lake Saimaa (south-east Finland). In fact, the
      probability of the suspect salmon originating from one of the regions that supply
      most of Finland's fish markets was found to be over 600 times higher than it
      originating from Lake Saimaa. When presented with this evidence, the offender
      confessed to purchasing the salmon at a local fish shop and criminal charges were
      laid. This study emphasizes the potential practical application of the individual
      assignment procedure, in particular the usefulness of confidently excluding
      populations as the origin of an individual. A similar strategy could be also
      used, for example in suspected cases of illegal poaching, in order to assign or
      exclude individuals from originating from a claimed population.

PMID- 11467435
TI  - Quantitative evaluation of hypothermia, hyperthermia, and hemodilution on
      coagulation.
AB  - The purpose of this study was to investigate the effects of temperature change on
      the coagulation time of blood at two different hematocrit levels by using various
      coagulation-monitoring devices. The devices used in this study were the Bayer
      Rapid Point Coag Analyzers, Hemochron Jr. Signature, Hemochron Response,
      Medtronic ACT II, and Haemoscope Thrombelastograph. One unit of human bank blood
      was used in this study. The hematocrit level was adjusted to 40% and 20%. A
      control bath and experimental bath were set up. Control blood was maintained at
      37 degrees C and tested every 45 +/- 15 min throughout the experimental period of
      6 h to demonstrate the stability of the model. The experimental blood was tested
      at temperature points of 37, 32, 27, 32, 37, 42, and 37 degrees C. Activated
      clotting time (ACT) tended to increase when the temperature was initially
      decreased from 37 to 27 degrees C, which reached a statistically significant
      level when measured by the Hemochron Response at both the 20% (147 +/- 10.7 to
      159.3 +/- 11.0, p < .0332) and 40% hematocrit level (130 +/- 14.9 to 152.1 +/-
      19.7, p < .0148). ACT was decreased significantly (p < .05) when the temperature
      was increased to 42 degrees C as measured by all machines except the Hemochron
      Jr. Signature at the 20% hematocrit level. ACT was significantly higher (p < .05)
      at a 20% hematocrit level as compared to that at a 40% hematocrit level on all
      devices for the majority of temperature points. These data suggested that
      hypothermia only increased ACT when measured by a macrosample device requiring a
      milliliter sample (Hemochron Response). However, hemodilution induced
      anticoagulatory effects and hyperthermia caused an acceleration in coagulation by
      all devices utilized in this study.

PMID- 11467436
TI  - Myocardial protection of warm blood cardioplegic induction during cardiopulmonary
      bypass.
AB  - In his prospective randomized clinical study, we evaluated the myocardial
      protection of warm blood cardioplegic induction and cold blood cardioplegic
      induction, respectively, during cardiopulmonary bypass. Twenty-eight adult
      patients who underwent valve replacement were randomly divided into two groups:
      group T (14 cases) received cold (6-8 degrees C) blood cardioplegic induction
      after ECG showed straight line induced by warm (35-37 degrees C) blood
      cardioplegia; whereas, group C (14 cases) received cold blood cardioplegic
      induction only. The effects of myocardial protection of both cardioplegic
      inductions were evaluated by clinical outcomes, myocardial biochemistry index
      (cardiac troponin T, cTnT), and myocardial automorphology. The ratio of
      myocardial auto resuscitation was significantly higher in group T (93%) than that
      in group C (50%). Only one case in group T (7%) and three cases in group C (21%)
      needed temporary pacemakers. No case in group T (0%) and five cases (36%) in
      group C received dopamine. The postoperative mechanical ventilation time and ICU
      stay time of group T were shorter than those of group C. Myocardial biochemistry
      indexplasma level of cTnT in group T was lower than that of group C immediately
      and 6 h after cardiopulmonary bypass. Myocardial morphology-group T had
      comparably better outcomes than group C. We concluded that warm blood
      cardioplegic induction during cardiopulmonary bypass, compared with cold blood
      cardioplegic induction, provides better myocardial protection.

PMID- 11467437
TI  - Effect of cardiopulmonary bypass on a patient with endocarditis and malaria.
AB  - Knowledge about the effects of cardiopulmonary bypass on malarial patients is
      scant. Malaria-induced hemolysis can exercerbate by performing extracorporeal
      circulation on a patient infected with Plasmodium and may, therefore, lead to a
      critical hemolysis jeopardizing the clinical outcome. A 52-year-old patient
      suffering from malaria and endocarditis was scheduled for urgent aortic valve
      replacement. During extracorporeal circulation, free hemoglobin showed an
      increase to maximum of 392.5 mg/L (normal range < 50 mg/L), while haptoglobin
      decreased to the lowest value of 0.56 g/L (normal range 0.3-2.0 gL). Although
      hemolysis increased, pump run, weaning, and the postoperative course were
      uneventful.

PMID- 11467438
TI  - Cardiopulmonary support for emergent innominate artery repair complicating
      tracheal surgery.
AB  - Innominate artery rupture is a rare, but usually fatal, complication of tracheal
      stenosis. Although prevention is key, prompt, appropriate intervention can be
      life saving. Hemorrhage and airway must simultaneously be controlled. Most deaths
      occur from exsanguination with adequate ventilation before surgical repair can be
      effected. In the ideal situation, the event would occur in the operating room. We
      report on just such a case with concomitant respiratory failure requiring
      cardiopulmonary support in order to accomplish definitive therapy.

PMID- 11467439
TI  - Use of ecarin clotting time (ECT) with lepirudin therapy in heparin-induced
      thrombocytopenia and cardiopulmonary bypass.
AB  - Heparin-induced thrombocytopenia (HIT) is described as an allergy-like adverse
      reaction to heparin. It is a potentially severe complication of heparin therapy
      that can result in serious or life-threatening venous or arterial thromboembolic
      events. In the United States, lepirudin (Aventis Pharma AG, Strasbourg, France)
      is an approved therapy for anticoagulation in patients with HIT requiring
      anticoagulation. Lepirudin is a recombinant form of hirudin, a leech enzyme that
      is a highly specific direct inhibitor of thrombin. Lepirudin monitoring during
      surgery can be managed with ecarin clotting time (ECT) (Cardiovascular
      Diagnostics, Inc., Raleigh, NC), which has recently been approved as a
      humanitarian device exemption (HDE) for use in the United States in the
      management of HIT with cardiopulmonary bypass. This case report describes a
      patient with HIT who was managed successfully with lepirudin and ECT during
      coronary artery bypass grafting.

PMID- 11467440
TI  - Neuromonitoring in the cardiopulmonary bypass surgical patient: clinical
      applications.
AB  - Intraoperative multimodality neurodiagnostic monitoring utilizing a transcranial
      Doppler, electroencephalography (EEG), and cerebral oximetry has been shown to
      reduce the incidence of neurological complications greatly. Potential problems
      affecting the brain can be detected and resolved or managed before disastrous
      consequences result. The use of multimodality neuromonitoring combined with
      traditional hemodynamic monitoring provides the clinician with additional data to
      manage the cardiac/vascular surgical patient better. Because the brain has the
      highest blood flow and metabolic demand of any organ, it seems the ideal and most
      logical place to monitor the adequacy of body perfusion. This review discusses
      our experiences and research over the last decade with the use of multimodality
      EEG monitoring on cardiopulmonary bypass surgical patients.

PMID- 11467441
TI  - Effect of partial-filling autotransfusion bowls on the quality of reinfused
      product.
AB  - Intraoperative autotransfusion is used in a variety of surgical procedures with
      the quantity of blood loss dependent upon numerous factors. These procedures may
      or may not produce a full autotransfusion bowl. The inadequate removal of
      contaminants has been correlated to the incomplete filling of bowls, resulting in
      a condition called "Salvaged Blood Syndrome." The purpose of this study was to
      assess the quality of aspirated whole blood after processing with an
      autotransfusion system using various fill volumes and two wash volumes. An in
      vitro circuit was designed to mimic the mechanical effects of extracorporeal flow
      on blood. Twenty-four Baylor-style bowls were filled at 400 mL min(-1) and washed
      at 300 mL min(-1). Two wash volumes, 1000 and 2000 mL, and three bowl volumes:
      low, mid, and full, were used in this study. The bowl volumes were determined by
      using red cell quantities of 60, 100, and 135 mL for the low-fill, mid-fill, and
      full bowls, respectively. Samples were drawn pre-autotransfusion and post
      autotransfusion and analyzed for plasma-free hemoglobin, IL-8, white blood cell
      count, platelet count, albumin, and total protein. All data were analyzed using
      one-way analysis of variance (ANOVA) with significance accepted at p > or = .05.
      Plasma-free hemoglobin levels and hematocrit were concentrated significantly (p <
      .05) as bowl volume increased. A significant difference in IL-8 levels was found
      in the wash volumes in the low-fill bowls (p < .02). Platelet count was
      significantly decreased between the full bowl with 1000 mL wash and the full bowl
      with 2000 mL wash (p < .0004). Total protein reduction was significantly less in
      the low-fill bowl with 1000 mL wash as compared to the other bowl treatments (p <
      .05). In conclusion, the quality of the washed product did not vary significantly
      between fill or wash volumes, with the exception of the low-fill bowl with 1000
      mL wash.

PMID- 11467442
TI  - Coronary artery bypass grafting with and without cardiopulmonary bypass: a
      comparison analysis.
AB  - Coronary artery bypass grafting (CABG) using stabilization devices in place of
      the heart-lung machine is being performed on a wide range of patients. This study
      retrospectively compared the performance of off-pump coronary artery grafting
      bypass (OPCAB) with conventional bypass patients over the same 6-month period at
      The Medical University of South Carolina. Data were collected and compared from
      the National Cardiac Database of the Society of Thoracic Surgeons (STS).
      Parameters studied included age, gender, left ventricular ejection fraction
      (LVEF), previous myocardial infarction (MI), disease severity, number of grafts,
      complications, blood usage, ventilation times, operating room (OR) time, and
      hospital length of stay (LOS). There were no significant difference between the
      patient groups with regard to age, gender, LVEF, previous MI, predicted
      mortality, and LOS. Operative mortality was also similar in the two groups:
      conventional bypass 4/117 (3%) and OPCAB 2/86 (2%). The conventional bypass
      patients (CPB) had significantly (p < 0.05) more diseased vessels (2.9 vs. 2.6)
      and distal grafts (4.1 vs. 2.7), as compared to the OPCAB group. OPCAB procedures
      resulted in significantly (p < 0.05) lower mean OR time (365 min vs. 406 min) and
      reduced mean postoperative ventilation hours (3.4 vs. 8.3 hours), as compared to
      conventional bypass. There were significantly (p < 0.05) fewer blood transfusions
      in the OPCAB group (1.1 units vs. 2.4 units), and the percentage of patients
      transfused blood was significantly less (34.9% vs. 57.3%). Nine out of 95 (9.5%)
      of patients who presented for OPCAB were converted to conventional bypass.
      Although there may be potential benefits to OPCAB, further studies must be
      directed at determining those patients who would benefit most from CABG using the
      off-pump technique.

PMID- 11467443
TI  - Carbon dioxide field flooding: a retrospective study.
AB  - The carbon dioxide surgical field flooding technique has long been tried with
      varying degrees of success. A recent revival of the technique that began over 40
      years ago in cardiac surgery, has brought promise as well as improved results
      attributable to improved technology. Studies at JFK Medical Center have been very
      successful using the carbon dioxide surgical field-flooding technique.
      Establishing new guidelines will assist other institutions in attempting this
      "old" technique with renewed success. Modern, more efficient equipment make use
      of carbon dioxide to displace intracardiac gases a safe procedure. The carbon
      dioxide field-flooding technique is safer, easier, and more efficacious than
      traditional de-airing techniques. This study shows that a long-standing procedure
      is valuable by observing the results, and, retrospectively evaluating stroke
      rates among cardiac valve cases at the hospital.

PMID- 11467444
TI  - Effects of ultrafiltration on enoxaparin: an in vitro analysis.
AB  - The use of low molecular weight heparins (LMWH) as an anticoagulant in the
      heparin-resistant patient poses challenges during cardiopulmonary bypass (CPB).
      The ultrafiltrability of LMWH has not been previously examined. The purpose of
      this study was to determine the effects of continuous ultrafiltration on the
      concentraton of a LMWH, enoxaparin. An in vitro analysis was performed using
      fresh whole human blood and an extracorporeal circuit containing four parallel
      ultrafiltrators and a cardiotomy reservoir with an integrated heat exchanger.
      Constant conditions included temperature (37 degrees C), flow (0.20 L-min(-1))
      transmembrane pressure (200 mmHg), and hematocrit (25 +/- 2%). Samples were
      collected at the inlet, outlet, and ultrafiltrate line at one and three min for
      one control trial and again for each of the four hemoconcentrators following the
      bolus of enoxaparin. Coagulation measurements included a viscoelastic monitor
      (TEG), activated clotting time (ACT), activated partial thromboplastin time
      (aPTT), and quantitative analysis utilizing a membrane-based electrode for
      potentiometric measurement of polyanionic concentrations of enoxaparin.
      Enoxaparin concentration, from inlet to outlet, increased from 2.95 +/- 0.64 to
      5.89 +/- 0.95 (p < .001) at 1 min and 4.24 +/- 0.49 to 7.89 +/- 0.606 (p < .001)
      at 3 min. Kinetic clot activity, as assessed by the TEG index, decreased from 
      3.8 +/- 2.5 vs. -10.5 +/- 6.0; (p < .01) pre- to postultrafiltrator samples after
      3 min. ACT and aPTT results demonstrated no significant change. In conclusion,
      this study demonstrates enoxaparin is concentrated with the use of continuous
      ultrafiltration. Functional coagulation studies also indicate a concentrating
      effect, primarily via the TEG.

PMID- 11467445
TI  - Introduction: Signaling in mammary development and tumorigenesis.

PMID- 11467446
TI  - The ras signaling pathway in mammary tumorigenesis and metastasis.
AB  - The Ras superfamily of GTPases act as important regulatory switches to co
      ordinate extracellular stimuli with activation of intracellular signaling
      pathways and appropriate biological responses. The Ras branch of this superfamily
      includes H-, K- and N-Ras, which are commonly mutated in particular human
      cancers, but notably not in those of the breast. Instead, in breast cancer the
      signaling pathways involving these GTPases may be upregulated due to increased
      coupling to growth factor receptors or other tyrosine kinases commonly
      overexpressed in this disease, or increased expression of regulators, the Ras
      protein itself, or downstream effectors. Functional studies utilizing both in
      vitro and in vivo models demonstrate that Ras signaling can regulate a variety of
      endpoints relevant to breast cancer progression, including anchorage dependent
      and independent growth, tumorigenesis, steroid sensitivity and invasion. Finally,
      analysis of the processing and signaling mechanisms of the Ras superfamily has
      identified potential targets for therapeutic intervention.

PMID- 11467447
TI  - Stat transcription factors in mammary gland development and tumorigenesis.
AB  - Two members of the Stat family of transcription factors play a vital role in
      mouse mammary gland development. Stat5a was originally described as a regulator
      of milk protein gene expression and was subsequently shown to be essential for
      mammary development and lactogenesis. In contrast, Stat3 is an essential mediator
      of apoptosis and post-lactational regression. Other members of the Stat family
      may have specific, but as yet undemonstrated, functions in mammary development.
      However, since Stat1 activity is regulated during mammary development in a
      pattern different from Stats 3 and 5, this factor too may have a functional role.
      Although both Stat4 and Stat6 are expressed in mammary tissue, it seems unlikely
      that they will have a significant function as each of these Stats is activated in
      response to a limited number of cytokines. Given the essential regulatory roles
      of Stat signaling molecules in mammary development, it was not surprising to
      discover that constitutively activated Stat factors are a feature of human breast
      cancers. Sustained Stat activity has also been described in a variety of tumors
      including leukemias. The cause of this sustained activation is not clear but
      probably involves mutation of one of the many Stat regulatory proteins or
      dysregulation of other signaling pathways which modulate Stat activity. It is now
      important to understand the mechanism of constitutive Stat activity and to
      develop strategies which will abrogate aberrant Stat signaling in tumors in vivo.

PMID- 11467448
TI  - Role of Ets transcription factors in mammary gland development and oncogenesis.
AB  - PEA3 is the founding member of a subfamily of closely related ets genes that
      includes ER81 and ERM. PEA3 is expressed in the epithelial cells of mammary buds
      at the time that these first appear during mouse embryogenesis, and it is
      differentially expressed during postnatal mammary gland development. PEA3
      expression is highest at the onset of puberty and during early pregnancy, times
      of extensive epithelial outgrowth and branching. PEA3 is expressed in
      undifferentiated epithelial cap cells of terminal end buds, and in differentiated
      myoepithelial cells of ducts and alveoli. Loss-of-function mutations in the PEA3
      gene compromise mammary ductal branching at the onset of puberty and early during
      pregnancy. PEA3 is overexpressed in the vast majority of human breast tumors and
      in nearly all of the HER2-positive subclass of such tumors. PEA3 is similarly
      overexpressed in transgenic mouse models of this malignancy. Expression of
      dominant-negative PEA3 in the mouse mammary gland of MMTV-HER2 transgenic mice
      dramatically delays the onset and reduces the incidence of mammary tumors. Hence
      PEA3 and/or its close relatives play key regulatory roles in both mammary gland
      development and oncogenesis.

PMID- 11467449
TI  - Myc and mammary cancer: Myc is a downstream effector of the ErbB2 receptor
      tyrosine kinase.
AB  - The proto-oncogene c-myc encodes a transcription factor which plays a major role
      in the regulation of normal cellular proliferation and is aberrantly expressed in
      many breast tumors. In a normal cell Myc expression levels are tightly regulated
      being subject to many layers of control. Errantly expressed Myc collaborates with
      other oncogenes to promote transformation. In this review we will focus on the
      association between abnormal Myc expression and mammary cancer. In particular, we
      will discuss the role of Myc as a downstream effector of the ErbB2 receptor
      tyrosine kinase which is overexpressed and constitutively activate in many
      mammary tumors. The cooperation between Myc and ErbB2 in transformation will be
      discussed in relation to clinical studies on Myc in human cancer and with
      consideration of transgenic models of Myc-induced mammary cancer. Data from our
      laboratory will be presented showing that deregulated ErbB2 activity strongly
      stimulates cytoplasmic signaling pathways which in turn impinge on Myc at
      multiple levels causing its deregulated expression.

PMID- 11467450
TI  - Notch signaling in mammary gland tumorigenesis.
AB  - The Notch receptor protein and its signaling pathway have been well conserved
      throughout evolution and appear to be pivotal components in cell fate decisions
      during development. Recent studies suggest that, depending on the cellular and
      developmental context, Notch signaling may also affect cell proliferation and
      programmed cell death. Mammals have four related Notch genes. One of these,
      designated Notch-4, was found to be a common integration site for the mouse
      mammary tumor virus in mouse mammary tumors. One consequence of this type of
      viral integration event is the ectopic expression of the intracellular domain of
      Notch-4 that corresponds to a gain-of-function mutation. Expression of
      "activated" Notch-4 in mammary epithelium has profound effects on mammary gland
      development and tumorigenesis. In this review, we briefly summarize the structure
      and function of the Notch receptor, as well as the components that comprise and
      modify the signaling pathway. Finally we discuss the potential role of Notch in
      mammary gland development and tumorigenesis.

PMID- 11467451
TI  - Wnt signaling and mammary tumorigenesis.
AB  - Wnt expression patterns during mammary development support a role for Wnts in
      breast development and in mammary epithelial responses to systemic hormones. The
      deregulation of Wnt signaling also plays a role in breast cancer. Activation of
      the Wnt signaling pathway is a major feature of several human neoplasias and
      appears to lead to the cytosolic stabilization of a transcriptional co-factor,
      beta-catenin. This co-activator can then regulate transcription from a number of
      target genes including the cellular oncogenes cyclin D1 and c-myc. This review
      will summarize the current state of knowledge of Wnt signal transduction in a
      range of model systems and will then address the role of Wnts and Wnt signaling
      in mammary development and cancer.

PMID- 11467452
TI  - Hedgehog signaling in mouse mammary gland development and neoplasia.
AB  - Genetic analyses of two hedgehog signal transduction network genes, Patched-1 and
      Gli2, has demonstrated a critical role for hedgehog signaling in mediating
      epithelial-stromal tissue interactions during ductal development. Disruption of
      either gene leads to similar, yet distinct, defects in ductal morphogenesis.
      Defects are mainly ductal dysplasias that closely resemble some hyperplasias of
      the human breast. Phenotypic analyses have been coupled with in situ
      hybridization, transplantation and tissue recombination analyses to formulate a
      model for tissue compartment-specific control of mouse mammary gland development
      by hedgehog signaling. In addition, the similarities among hedgehog mutation
      induced ductal dysplasias and human breast pathologies suggest a role for altered
      hedgehog signaling in the development of mammary cancer.

PMID- 11467453
TI  - TGF-beta signaling in mammary gland development and tumorigenesis.
AB  - Ligands of the TGF-beta superfamily are unique in that they signal through
      transmembrane receptor serine-threonine kinases, rather than tyrosine kinases.
      The receptor complex couples to a signal transduction pathway involving a novel
      family of proteins, the Smads. On phosphorylation, Smads translocate to the
      nucleus where they modulate transcriptional responses. However, TGF-betas can
      also activate the mitogen-activated protein kinase (MAPK)4 pathway, and the
      different biological responses to TGF-beta depend to varying degrees on
      activation of either or both of these two pathways. The Smad pathway is a nexus
      for cross-talk with other signal transduction pathways and for modulation by many
      different interacting proteins. Despite compelling evidence that TGF-beta has
      tumor suppressor activity in the mammary gland, neither TGF-beta receptors nor
      Smads are genetically inactivated in human breast cancer, though receptor
      expression is reduced. Possible reasons are discussed in relation to the dual
      role of TGF-beta as tumor suppressor and oncogene.

PMID- 11467454
TI  - Regulation of mouse mammary gland development and tumorigenesis by the ERBB
      signaling network.
AB  - The four ERBB receptors and their multiple polypeptide ligands are differentially
      expressed during development of the mouse mammary gland. Profiles suggest that
      ERBB1/EGF receptor (EGFR)4 and ERBB2/Neu are required during ductal
      morphogenesis, whereas the Neuregulin (NRG) receptors, ERBB3 and ERBB4, are
      preferentially expressed through alveolar morphogenesis and lactation. Consistent
      with these profiles, recent gene knockouts established that EGFR and its ligand,
      Amphiregulin (AR), are essential for ductal morphogenesis in the adolescent mouse
      and likely provide the required epithelial-stromal signal. In contrast, the
      phenotypes of transgenic mice expressing dominant negative ERBB2 and ERBB4
      proteins suggest that these receptors differentially act to promote or maintain
      alveolar differentiation. This view of ERBB action provides a conceptual
      framework for future testing using more sophisticated conditional knockout
      models. New or existing transgenic mice are also being used to better understand
      the contributions of ERBB receptors and ligands to mammary tumorigenesis, as well
      as to more closely mimic the human disease. Recent studies have focused on
      defining molecular events in neoplastic progression, and in the case of
      ERBB2/Neu, the requirement for ERBB heterodimerization partners as well as the
      relative importance of gene amplification versus gene mutation. Collectively,
      these recent studies establish that normal development and homeostasis of the
      mammary gland is critically dependent on regulated ERBB signaling. They also
      illustrate the value of animal models in deciphering roles for the complex ERBB
      network in this dynamic tissue.

PMID- 11467456
TI  - Indications for implantable cardioverter defibrillator (ICD) therapy.

PMID- 11467457
TI  - Dual-coil vs single-coil active pectoral implantable defibrillator lead systems:
      defibrillation energy requirements and probability of defibrillation success at
      multiples of the defibrillation energy requirements.
AB  - AIMS: The aim of the study was to compare the defibrillation energy requirements
      and the probability of successful defibrillation at multiples of the minimum
      defibrillation energy requirements in active pectoral implantable defibrillators
      with single- and dual-coil lead systems. METHODS AND RESULTS: Eighty-three
      consecutive patients undergoing implantation of an active pectoral cardioverter
      defibrillator were randomized to receive a dual- or single-coil lead system.
      Defibrillators of two manufacturers with a fixed tilt biphasic defibrillation
      waveform were used. Defibrillation energy requirements were determined using a
      step-down defibrillation testing protocol. According to the randomization
      protocol, the patients were assigned to three additional consecutive
      defibrillation attempts during device implantation and during pre-discharge
      testing of either 1.0, 1.5 or 2.0 times the determined defibrillation energy
      requirement. Patients presenting defibrillation energy requirements > 15 J were
      excluded from analysis. Eighty of 83 patients (96%) completed the study protocol.
      Three patients were excluded due to elevated defibrillation energy requirements.
      The defibrillation energy requirements in the dual- and single-coil patient
      groups were 8.0 +/- 3.6 J and 8.4 +/- 3.7 J (ns), respectively. A comparable
      percentage of study patients showed defibrillation energy requirements <10 J
      (dual-coil: 88% vs single-coil: 83%). Defibrillation impedance was significantly
      different (dual-coil: 50 +/- 5.8 Ohm; single-coil: 39.8 +/- 4.2 Ohm). Regarding
      the probabilities of successful defibrillation, there were no significant
      differences between the two patient groups. The probabilities of defibrillation
      at the three multiples of the defibrillation energy requirement using a dual- and
      single-coil lead system were 82, 89.7 and 93.6 and 77.8, 94.1 and 95.8%,
      respectively (P=0.88, P=0.42, P=0.62, respectively). CONCLUSIONS: Dual- and
      single-coil active pectoral defibrillator systems show no difference in
      defibrillation energy requirements and no difference in the probability of
      successful defibrillation at multiples of the minimum defibrillation energy
      requirement. The use of more simplified defibrillator lead systems may contribute
      to a future lead design focusing on improvement in lead durability.

PMID- 11467455
TI  - Phosphatidylinositol 3' kinase signaling in mammary tumorigenesis.
AB  - Suppression of apoptosis is now recognized as a key contributory element to
      tumorigenesis in animal models and human cancer. The phosphatidylinositol 3'
      kinase pathway plays a seminal role in cell death suppression or "survival
      signaling." Over the past 5 years, the molecular mechanisms by which this pathway
      exerts its death suppressive effects have slowly been revealed. This review
      summarizes the players involved, their importance in human cancer and their
      specific involvement in breast cancer.

PMID- 11467458
TI  - Initial clinical experience with a new arrhythmia detection algorithm in dual
      chamber implantable cardioverter defibrillators.
AB  - AIM: Inappropriate therapy, due to poor discrimination of supraventricular
      tachycardia (SVT) from ventricular tachycardia (VT) remains a major problem in
      patients with an implantable cardioverter defibrillator (ICD). Theoretically, the
      addition of atrial sensing in discrimination algorithms should improve this
      differentiation. The aim of the study is to evaluate the performance of a new
      tachycardia discrimination algorithm, SMART Detection. METHODS AND RESULTS:
      Twenty-six patients received a non-thoracotomy ICD system (Phylax AV, Biotronik,
      Germany). All documented spontaneous arrhythmia episodes were analyzed. During a
      mean follow-up of 8 months, a total number of 139 events with stored electrograms
      were recorded in 12 patients. The final diagnosis was ventricular fibrillation
      (VF) or polymorphic VT (n=20), monomorphic VT (n=69), SVT (n=26), other
      ventricular arrhythmia (n=3) and T wave oversensing (n=21). In 6 episodes a dual
      tachycardia was present. Considering SVT episodes, inappropriate therapy occurred
      in 2 cases of atrial flutter due to stable ventricular rate (<30 ms), 1 case of
      atrial tachycardia and 2 cases of sinus tachycardia due to a sudden onset (>
      10%). CONCLUSION: With the SMART Detection algorithm, discrimination of VT from
      SVT achieved a sensitivity of 100%, with an accuracy of 95.6% for all ventricular
      arrhythmias. In the case of SVT, the algorithm appropriately detected and
      inhibited therapy in 88% of atrial fibrillation.

PMID- 11467459
TI  - Value of non-invasive and invasive studies in patients with bundle branch block,
      syncope and history of myocardial infarction.
AB  - The prognosis of patients with bundle branch block (BBB) and myocardial
      infarction (MI) is poor, particularly for patients suffering from syncope. The
      purpose of this study was to investigate the diagnostic value of some techniques
      for the evaluation of the mechanism of syncope in patients with MI and BBB and
      their prognosis. METHODS: We prospectively obtained the results of clinical
      history, 24 h Holter monitoring, left ventricular ejection fraction (LVEF),
      signal-averaged ECG (SAECG) and programmed ventricular stimulation in 130
      patients with syncope, MI and BBB. 81 of them had right (R)BBB and 49-left
      (L)BBB. RESULTS: Ventricular tachycardia (VT) was identified as the main cause of
      syncope in patients with MI and BBB: 68% of them had inducible VT. The
      sensitivity (se) and specificity (sp) of non sustained VT on Holter monitoring
      for the detection of VT were respectively 42.5 and 47% in patients with RBBB, 62
      and 36% in those with LBBB; se and sp of LVEF <40% were 67.5% and 65% in patients
      with RBBB, 85 and 9% in those with LBBB; se and sp of the combination of 2 of the
      3 SAECG criteria, QRS duration > 155 ms, LAS duration >30 ms and RMS 40 < 17
      microV were respectively 50 and 57% in patients with RBBB; se and sp of the
      combination of 2 of the 3 criteria QRS duration >165 ms, LAS duration >40 ms and
      RMS 40 <17 microV were 73 and 55.5%) in patients with LBBB. During the follow-up
      (4.7 years +/- 2.5), 12 patients died suddenly and 12 patients died from heart
      failure. Univariate and multivariate analysis revealed than only the induction of
      VT was a significant predictor of sudden death. A long QRS duration (> 165 ms)
      and induction of VT were independent predictors of total cardiac mortality.
      CONCLUSION: Among noninvasive studies, only the determination of filtered QRS
      duration was a significant predictor of cardiac mortality in the case of a
      prolongation (> 165 ms). Sudden death was only predicted by the induction of
      sustained VT. Because of the high incidence of inducible sustained VT, the low
      value of Holter monitoring and decreased LVEF for the prediction of ventricular
      arrhythmias and the poor prognosis of patients with inducible VT and low LVEF,
      systematic programmed ventricular stimulation is indicated in patients with MI,
      syncope and BBB, whatever the non-invasive studies results.

PMID- 11467460
TI  - Thrombogenicity of radiofrequency ablation procedures: what factors influence
      thrombin generation?
AB  - AIMS: Thromboembolic complications have been reported after radiofrequency
      ablation but the low incidence of overt clinical events has been a limitation to
      the study of factors affecting thrombogenic risk. The aim of this study was to
      determine whether radiofrequency ablation has a procoagulant effect and to
      examine variables that affect thrombio generation. METHODS AND RESULTS: Thirty
      seven consecutive patients who underwent radiofrequency ablation were studied
      prospectively. Blood samples were assayed for thrombin-antithrombin III (TAT) and
      d-dimer (DD) at five different time points: (1) baseline; (2) after sheath
      insertion; (3) after electrophysiological study but before radiofrequency
      ablation; (4) at completion of the procedure; and (5) 24 h post-procedure. TAT
      levels were within the normal range at baseline and increased significantly after
      sheath insertion from 2.1 +/- 1.2 microg l(-1) to 13.3 +/- 16.0 microg l(-1)
      (P<0.01). Levels increased further to 24.0 +/- 19.9 microg l(-1) (P<0.01) after
      electrophysiological study but did not increase after radiofrequency ablation.
      TAT normalized at 24 h. DD increased significantly from baseline values (230.2 +/
      176.8 ng ml(-1)) to 285.4 +/- 237.4 ng ml(-1) (P=0.019) after sheath insertion.
      There was a further significant increase after electrophysiological study to
      423.4 +/- 324.3 ng ml(-1) (P<0.01), and a slight but non-significant increase to
      464.4 +/- 307.4 ng ml(-1) after radiofrequency ablation (P=0.159). DD remained
      elevated at 24 h. Procedure duration was the only variable that correlated with
      the relative increase in TAT and DD. The patients with the longest procedure
      durations had more catheters inserted, more radiofrequency applications and
      largely consisted of accessory bypass tract-mediated tachycardias. Heparin
      administration significantly blunted the relative increase in TAT after
      radiofrequency ablation (P=0.005). CONCLUSION: Radiofrequency ablation procedures
      confer an increased risk of thrombosis. Catheterization and diagnostic study
      contribute largely to the thrombogenic stimulus. Thrombogenicity is increased in
      prolonged, complex procedures and is decreased in patients who have been
      administered heparin during the procedure.

PMID- 11467461
TI  - Electrochemical potentials during radiofrequency energy delivery: a new method to
      control catheter ablation of arrhythmias.
AB  - AIMS: Thermal injury of subendocardial tissue leads to a release of electrolytes
      and free radicals from the intracellular site creating a change in
      electrochemical potential (eP) between the distal and the proximal catheter tip
      electrodes. The aim of the study was to verify the detection of ablation-induced
      release of electrolytes and free radicals and to assess the suitability of
      control-line energy delivery at ablation by measuring eP. METHODS AND RESULTS: In
      vitro tests under constant flow conditions were performed in a 101 bath of
      physiological saline solution or bovine blood. Endomyocardial preparations of
      fresh bovine hearts were used. Closed-loop temperature-controlled, irrigated and
      closed-loop eP-controlled ablations were performed. In vivo animal investigations
      were performed in six anaesthetized and ventilated pigs. The existence of the eP
      was established in the tank model and was confirmed in animal investigations.
      High correlations were found between eP and catheter tip temperature (r=0.87) and
      between maximum eP and induced lesion size (r=0.85). Also a high correlation
      (r=0.85, P<0.001) was found between eP and lesion volume. CONCLUSIONS: Control of
      energy delivery during RF ablation by the measurement of eP is feasible. In
      comparison with temperature controlled RF ablation, ablation guided by eP
      measurement revealed a superior correlation with induced lesion size. Especially
      during cooled radiofrequency catheter ablation eP is the only parameter for
      control of energy delivery.

PMID- 11467462
TI  - Prospective evaluation of a simplified approach for common atrial flutter radio
      frequency ablation with only two catheters.
AB  - Intra-atrial conduction block within the inferior vena cava-tricuspid annulus
      isthmus (IVCT) has been shown to predict successful common atrial flutter
      ablation. However, its demonstration requires the use of several electrode
      catheters and mapping of the line of block. The aim of this study was
      prospectively to test the feasibility of a simplified ablation procedure using
      only two catheters. METHODS: Radio frequency (RF) ablation of common atrial
      flutter was performed in 30 patients with the sole use of a catheter for atrial
      pacing and a RF catheter. RF ablation lesions were created in the IVCT. Surface
      ECG criteria were used to monitor the conduction within the IVCT. The end point
      during low lateral atrial pacing was an increment in the interval between the
      pacing artefact and the peak of the R wave in surface lead II >50 ms and
      clockwise rotation of the P wave axis beyond -30 degrees and inferiorly. Then,
      the line of lesions was mapped during atrial pacing with the RF catheter.
      Additional RF lesions were applied if mapping disclosed a zone of residual
      conduction. Otherwise the procedure was stopped if mapping showed parallel double
      potentials all along the line. Finally, the block was reassessed with a 'Halo'
      catheter. RESULTS: Surface ECG criteria were met in 26 patients. Mapping the line
      of lesions showed a complete corridor of parallel double potentials in these 26
      cases and in 3 of the 4 patients in whom ECG criteria were not met. Conduction
      evaluated with the Halo catheter showed bi-directional complete block in these 29
      patients. After a follow-up of 16 +/- 4 months there was no recurrence of atrial
      flutter. CONCLUSION: Surface ECG criteria combined with mapping of the line of
      block demonstrate evidence of bi-directional IVCT block. This simplified RF
      ablation of common atrial flutter is feasible with a low recurrence rate.

PMID- 11467463
TI  - Electrophysiological properties of the atrioventricular node and ageing: evidence
      of a lower incidence of dual nodal pathways in the elderly.
AB  - AIMS: The purpose of this study was to investigate the relationship between the
      incidence of dual atrioventricular (AV) nodal pathways and age. Age-related
      changes in the AV node electrophysiological properties have rarely been
      investigated. AV nodal re-entrant tachycardia is more frequent in the young than
      in the elderly. METHODS AND RESULTS: From 1988 to 1998, premature atrial
      stimulation was performed in 1,435 patients referred to our institution for
      transoesophageal electrophysiological study. 1,276 patients (89%) with a
      diagnosis of ventricular pre-excitation, supraventricular arrhythmia or AV block
      were excluded. The study cohort consisted of the remaining 159 patients (11%) of
      the whole group) referred for syncope (8.2% of the subgroup), suspected
      ventricular pre-excitation (10.7%), suspected sinus node dysfunction (52.8%) or
      undetermined palpitations (28.3%). The 159 study patients were divided into 3
      groups according to age: group A (11-30 years, 50 patients), group B (30-60
      years, 35 patients) and group C (>60 years, 74 patients). A dual AV nodal pathway
      was found in 16 patients of group A (32.0%), 6 patients of group B (17.1%) and 8
      patients of group C (10.8%), the difference between group A and group C being
      significant (P<0.05). CONCLUSION: The incidence of dual AV nodal pathways
      decreases with ageing, suggesting that the AV node undergoes age-related
      electrophysiological changes. This finding could explain the uncommon onset of AV
      nodal re-entrant tachycardia in the elderly.

PMID- 11467464
TI  - Evaluation of the quality of rate adaptation algorithms for cardiac pacing.
AB  - The aim of this study was a comparative evaluation of some commonly used
      pacemaker control parameter combinations and algorithms for heart rate (HR)
      reconstruction. The quality of heart rate reconstruction was estimated comparing
      the reconstructed heart rate and intrinsic heart rate on the basis of a healthy
      person model. The model was developed on the basis of simultaneous measurement of
      intrinsic HR and different control parameters, which can electrically be
      recorded: QT-interval, (QT), ventilation (V)- and body movement activity (ACT).
      Relative mean square error (RMSE) between natural and reconstructed HR was used
      as a measure of HR reconstruction quality. It was shown that the results of
      linear and polynomial approximations for HR reconstruction practically coincided
      inside the range of interest for pacing in clinical practice 60-120 beats.min(-1)
      and there was no need to implement more complex algorithms. As for single
      parameter systems the QT parameter had better reconstruction accuracy compared
      with ACT and V. All double-parameter systems presented HR reconstruction error
      level of around 10% that were within the limits suitable for clinical practice.
      The application of more than two parameters for HR reconstruction seems to be
      unnecessary, as the triple-parameter models appeared not to improve remarkably
      the quality of HR reconstruction.

PMID- 11467465
TI  - The use of permanent pacemakers in the detection of cardiac arrhythmias.
AB  - AIMS: To compare pacemaker telemetry with simultaneous Holter recordings in the
      diagnosis of atrial fibrillation and to evaluate the STOP-AF study telemetry
      criteria for the presence of atrial fibrillation. METHODS AND RESULTS: 18
      consecutive patients enrolled in the STOP-AF study had simultaneous 24 h Holter
      recordings and down-loaded pacemaker telemetry. There was good agreement on heart
      rate, but the STOP-AF pacemaker criteria achieved only 57% sensitivity with 64%
      specificity for the presence of atrial fibrillation on Holter recording over 24
      h. False-positives appeared to result from far-field sensing while false
      negatives occurred with very short episodes of atrial fibrillation. The
      pacemaker's antitachycardia responses were not specific for the presence of
      atrial fibrillation. CONCLUSION: Pacemaker telemetry is a potentially important
      source of data on cardiac arrhythmias. Further studies are required to define the
      limitations of these data in specific devices before they can be interpreted with
      confidence.

PMID- 11467466
TI  - Components of clinical trials for vasovagal syncope.
AB  - The time is ripe for adequately powered, randomized, placebo-controlled clinical
      trials in vasovagal syncope. Vasovagal syncope is a common syndrome, the symptoms
      of which can be troublesomely frequent. It is usually diagnosed by tilt-table
      testing, although this has persistent problems with both sensitivity and
      specificity. Patients with syncope and positive tilt tests have been the subjects
      of numerous studies of natural history, risk stratification, and treatment. This
      paper discusses studies of treatments for vasovagal syncope in the context of a
      classification of the levels of evidence that can be gleaned from clinical
      studies. The reasons for placebo-controlled trials are reviewed, as is the
      evidence for various methods of risk stratification. Data for power calculations
      are presented for the primary outcome, the time to the first syncope recurrence.
      Strengths and weakness of the four main types of outcomes for clinical trials are
      compared.

PMID- 11467467
TI  - An unusual cause of tachycardiomyopathy: incessant atypical AV nodal reentrant
      tachycardia induced by 1:2 AV conduction.
AB  - We report a 62-year-old female with cardiomyopathy mediated by incessant atypical
      atrioventricular nodal reentrant tachycardia, which was induced by 1:2
      atrioventricular conduction. Her arrhythmia was identified and cured by
      radiofrequency catheter ablation. Follow-up over the course of next 5 months the
      patient's cardiomyopathy dramatically improved.

PMID- 11467468
TI  - Symptomatic postictal cardiac asystole in a young patient with partial seizures.
AB  - This report describes a patient with complex partial seizures arising from the
      right temporal lobe who developed symptomatic sinus arrest following the end of
      his seizure activity. A ventricular pacemaker was implanted and was documented to
      function appropriately, preventing development of bradycardia associated symptoms
      during subsequent seizures. Possibly relevant cerebral structures are briefly
      discussed.

PMID- 11467469
TI  - Mammary cancer in humans and mice: a tutorial for comparative pathology.

PMID- 11467470
TI  - Comparative examination of cats with feline leukemia virus-associated enteritis
      and other relevant forms of feline enteritis.
AB  - Cats with feline leukemia virus (FeLV)-associated enteritis (FAE), enteritis of
      other known viral etiology (parvovirus [PV], enteric coronavirus [CoV]), and
      enteritis of unknown etiology with histologic features similar to those of FAE
      and PV enteritis (EUE) and FeLV-negative and FeLV-positive cats without
      enterocyte alterations were examined. Amount and types of infiltrating leukocytes
      in the jejunum and activity and cellular constituents of mesenteric lymph nodes,
      spleen, and bone marrow were determined. PV and CoV infections were confirmed by
      immunohistologic demonstration of PV and CoV antigen, ultrastructural
      demonstration of viral particles in the intestinal content, and in situ
      hybridization for PV genome. FeLV infection was detected by immunohistology for
      gp70, p27, and p15E. Latent FeLV infection was excluded by polymerase chain
      reaction methods for exogenous FeLV DNA. Enterocyte lesions involved the crypts
      in cats with PV enteritis, FAE, and EUE and the villous tips in cats with CoV
      enteritis. Inflammatory infiltration was generally dominated by mononuclear cells
      and was moderate in the unaltered intestine and in cats with PV enteritis and
      marked in cats with FAE, CoV enteritis, and EUE. In cats with EUE,
      myeloid/histiocyte antigen-positive macrophages were relatively numerous,
      suggesting recruitment of peripheral blood monocytes. Lymphoid tissues were
      depleted in cats with PV enteritis and with EUE but were normal or hyperplastic
      in cats with FAE. Bone marrow activity was decreased in cats with PV enteritis;
      in cats with FAE or EUE and in FeLV-positive cats without enterocyte alterations,
      activity was slightly increased. In cats with FAE and PV enteritis, a T-cell
      dominated response prevailed. EUE showed some parallels to human inflammatory
      bowel disease, indicating a potential harmful effect of infiltrating macrophages
      on the intestinal epithelium.

PMID- 11467471
TI  - Hepatic failure and hemochromatosis of Salers and Salers-cross cattle.
AB  - Hemochromatosis is rare in domestic mammals. Five clinical cases and one
      preclinical case of hemochromatosis were diagnosed in Salers and Salers-cross
      cattle. Clinical disease developed between 9 and 22 months of age. Animals were
      healthy until weaning but then lost weight, developed rough hair coats, and lost
      incisor teeth. In two animals, hemochromatosis was identified by liver biopsy,
      biochemical evidence of hepatic injury, and/or elevated transferrin saturation
      values. At necropsy, carcasses were thin, with firm dark brown livers and lymph
      nodes, soft bones, and brown-colored small bowel. The principal histologic
      changes were hepatocellular siderosis and periportal, bridging, and perivenular
      fibrosis. Siderocalcinosis involved collagen, elastin, reticulin, and basement
      membrane components in liver, lymph nodes, spleen, duodenum, and kidney. Hepatic
      iron concentrations in clinically affected cattle were 1,500-10,500 microg/g wet
      weight (reference range for cattle = <300 microg/ g). Ultrastructurally, the
      heaviest intrahepatic deposition was in hepatocytes, which contained large
      intracytoplasmic siderosomes. Iron deposition in bone was associated with
      osteopenia. Genetic analysis indicated a common ancestral bull in the pedigrees
      of five of six affected cattle; no pedigree was available for the remaining
      animal. Four dams of five affected animals were phenotypically normal and had
      histologically normal livers. Test mating of four cows to the ancestral bull
      resulted in a female calf that developed clinicopathologic and histologic
      evidence of preclinical hemochromatosis by 40 days of age. It was not possible to
      establish the pattern of inheritance because of the small number of pedigrees
      from affected cattle.

PMID- 11467472
TI  - Detection and localization of ApxI, -II and -III genes of Actinobacillus
      pleuropneumoniae in natural porcine pleuropneumonia in natural porcine
      pleuropneumonia by in situ hybridization.
AB  - In situ hybridization techniques that employed a nonradioactive digoxigenin
      labeled probe were used to detect and localize ApxI, II and III genes in tissue
      sections of pneumonic lung naturally infected with Actinobacillus
      pleuropneumoniae. In pigs infected with either serotype 2 or 6, a hybridization
      signal for apxIICA, apxIIICA, apxIBD, and apxIIIBD was detected, and in pigs
      infected with serotype 5, a hybridization signal for apxICA, apxIICA, and apxIBD
      was detected in the pneumonic lesions. A hybridization signal for apxIICA and
      apxIBD was detected in pigs infected with serotype 7. A strong hybridization
      signal for apx genes was seen in streaming degenerate alveolar leukocytes
      bordering zones of coagulative necrosis. Simultaneous detection of hybridization
      signals for the apxCA and apxBD genes provided scientific evidence that the
      expression of the apx genes could be potential indicators of the production of
      corresponding Apx toxins. This study demonstrates the expression of ApxI, II, and
      III genes in pneumonic lesions caused by A. pleuropneumoniae.

PMID- 11467473
TI  - Pathogenesis of experimental vesicular stomatitis virus (New Jersey serotype)
      infection in the deer mouse (Peromyscus maniculatus).
AB  - The pathogenesis of vesicular stomatitis virus (VSV) infection has not been
      investigated previously in native New World rodents that may have a role in the
      epidemiology of the disease. In the present study, 45 juvenile and 80 adult deer
      mice (Peromyscus maniculatus) were inoculated intranasally with VSV New Jersey
      serotype (VSV-NJ) and examined sequentially over a 7-day period. Virus was
      detected by means of immunohistochemistry and in situ hybridization in all
      tissues containing histologic lesions. Viral antigen and mRNA were observed
      initially in olfactory epithelium neurons, followed by olfactory bulbs and more
      caudal olfactory pathways in the brain. Virus also was detected throughout the
      ventricular system in the brain and central canal of the spinal cord. These
      results support both viral retrograde transneuronal transport and viral spread
      within the ventricular system. Other tissues containing viral antigen included
      airway epithelium and macrophages in the lungs, cardiac myocytes, and macrophages
      in cervical lymph nodes. In a second experiment, 15 adult, 20 juvenile, and 16
      nestling deer mice were inoculated intradermally with VSV-NJ. Adults were
      refractory to infection by this route; however, nestlings and juveniles developed
      disseminated central nervous system infections. Viral antigen also was detected
      in cardiac myocytes and lymph node macrophages in these animals. Viremia was
      detected by virus isolation in 35/72 (49%) intranasally inoculated juvenile and
      adult mice and in 17/36 (47%) intradermally inoculated nestlings and juveniles
      from day 1 to day 3 postinoculation. The documentation of viremia in these
      animals suggests that they may have a role in the epidemiology of vector-borne
      vesicular stomatitis.

PMID- 11467474
TI  - Immunohistochemical detection of apolipoprotein B-100 and immunoglobulins (IgA,
      IgM, IgG) in the splenic arteries of aging dogs.
AB  - Accumulation of lipids and hyalinosis in the splenic arteries of aged dogs are
      frequently detected by routine histopathologic examinations. The purpose of this
      study was to pinpoint the localization of canine apolipoprotein B-100 (CApoB-100)
      and immunoglobulins (IgA, IgM, IgG) in the splenic arteries of aging dogs (n =
      80) through the use of immunohistochemical techniques. CApoB-100 deposits were
      found in the subendothelial space, extracellular matrix, and atheromatous lesions
      in the tunica media of the arteries in dogs > or = 6 years of age. Foamy
      cytoplasm of the infiltrated macrophages was also CApoB-100 immunopositive. In
      dogs > or = 10 years of age, almost all central arteries were CApoB-100
      immunopositive. Hyaline deposits within the wall were characterized by
      immunopositivity against canine IgA, IgM, IgG, and albumin. Lipid accumulation in
      splenic arteries may be an age-related lesion and a precursor of the atheromatous
      plaques associated with splenic hemorrhage and infarcts later in life. In
      addition, deposition of immunoglobulins, probably mediated by immune complexes,
      may play an important role in the development of canine vascular diseases similar
      to human disease.

PMID- 11467475
TI  - Pathologic and immunohistochemical findings in naturally occuring West Nile virus
      infection in horses.
AB  - The pathologic and peroxidase immunohistochemical features of West Nile
      flavivirus (WNV) infection were compared in four horses from the northeastern
      United States and six horses from central Italy. In all 10 animals, there were
      mild to severe polioencephalomyelitis with small T lymphocyte and lesser
      macrophage perivascular infiltrate, multifocal glial nodules, neutrophils, and
      occasional neuronophagia. Perivascular hemorrhages, also noted macroscopically in
      two animals, were observed in 50% of the horses. In the four American horses,
      lesions extended from the basal nuclei through the brain stem and to the sacral
      spinal cord and were more severe than the lesions observed in the six Italian
      horses, which had moderate to severe lesions mainly in the thoracolumbar spinal
      cord and mild rhombencephalic lesions. WNV antigen was scant and was identified
      within the cytoplasm of a few neurons, fibers, glial cells, and macrophages. WNV
      infection in horses is characterized by lesions with little associated antigen
      when compared with WNV infection in birds and some fatal human infections and
      with other important viral encephalitides of horses, such as alphavirus
      infections and rabies.

PMID- 11467476
TI  - Comparison of tissue stages of Hepatozoon americanum in the dog using
      immunohistochemical and routine histologic methods.
AB  - American canine hepatozoonosis is caused by Hepatozoon americanum, a recently
      described species of apicomplexan protozoan parasite. An immunohistochemical
      procedure using a polyclonal antibody to sporozoites of H. americanum clearly
      identified asexual stages of H. americanum in canine striated muscle. The method
      also detects hepatozoa present in naturally infected coyotes and raccoons and
      reacts with certain other apicomplexans. Use of this immunohistochemical
      procedure confirms the canine intermediate host-parasite relationships that were
      presumptively established using conventional histopathologic methods.

PMID- 11467477
TI  - Expression of S100a, vimentin, NSE, and melan A/MART-1 in seven canine melanoma
      cells lines and twenty-nine retrospective cases of canine melanoma.
AB  - We evaluated the expression of vimentin, S100a, and Melan A/MART-1 (melanoma
      antigen recognized by T cells 1) in seven cell lines established independently
      from dogs with canine melanoma. We also compared routine immunostaining of 29
      clinical specimens from melanoma cases using vimentin, S100a, and neuron-specific
      enolase (NSE) with staining for Melan A/MART-1 as part of a diagnostic panel. All
      the cell lines were positive for expression of vimentin and S-100a. MelanA/MART-1
      expression was seen consistently in only two of the seven cell lines. Staining
      for Melan A/MART-1 was most intense near areas of heavy melanin pigmentation. All
      except one of the clinical specimens were positive for vimentin. S 100a was
      expressed in the majority of both pigmented (15/20, 75%) and amelanotic (8/9,
      88.8%) tumors. Seventeen of 29 (58.6%) tumors were positive for NSE. Melan A/MART
      1 was expressed in 18/29 (62%) tumors, including 90% of pigmented tumors, but in
      no amelanotic tumors. Intensity of Melan A/MART-1 staining correlated positively
      with biologic behavior, with seven malignant tumors showing negative to weak
      staining and 10 benign tumors showing moderate to strong staining. Three
      malignant tumors showed moderate to intense staining for Melan A/ MART-1. Our
      results suggest that expression of Melan A/MART-1 may be unstable in cultured
      cell lines. Assessment of both S100a and Melan A/MART-1 expression is useful to
      confirm a diagnosis of canine melanoma, and Melan A/MART-1 may be especially
      informative regarding the biologic behavior of these tumors.

PMID- 11467478
TI  - Colocalization of porcine reproductive and respiratory syndrome virus and porcine
      circovirus 2 in porcine dermatitis and nephrology syndrome by double-labeling
      technique.
AB  - Simultaneous detection of porcine reproductive and respiratory syndrome virus
      (PRRSV) and porcine circovirus 2 (PCV2) was achieved by a double-labeling
      technique using a combination of immunohistochemistry and in situ hybridization
      in five pigs with naturally occurring porcine dermatitis and nephropathy syndrome
      (PDNS). Both PRRSV and PCV2 were isolated from a homogenate of pooled skin and
      kidney from three pigs. PRRSV RNA was demonstrated by reverse transcription
      polymerase chain reaction (PCR) in skin, kidney, lymph node, and tonsil
      homogenates from all pigs. PCV2 DNA was demonstrated by PCR in kidney, lymph
      node, tonsil, liver, and lung homogenates from all pigs. For double-labeling
      studies, the tissue samples were processed sequentially, first by
      immunohistochemistry and then by in situ hybridization. The most consistent and
      intense staining for PRRSV and PCV2 was in the kidney, lymph node, and tonsil.
      PRRSV antigen and PCV2 DNA were also detected in the skin. This morphologic study
      is the first to confirm the presence of both PRRSV and PCV2 in the same tissues
      in pigs with naturally occurring PDNS.

PMID- 11467479
TI  - Hamster polyomavirus infection in a pet Syrian hamster (Mesocricetus auratus).
AB  - An approximately 8-week-old pet Syrian hamster (Mesocricetus auratus) with a 1
      week history of dyspnea, hyporexia, and ataxia was submitted for necropsy. On
      gross examination, the hamster had multiple abdominal adhesions and enlargement
      of the mesenteric lymph node. Histologic evaluation revealed multicentric
      lymphoma of the liver, jejunum, mesenteric lymph node, testicular fat pad, and
      epididymis. Based on the hamster's age and the type and distribution of the
      lymphoma, a presumptive diagnosis of hamster polyomavirus-induced lymphoma was
      made. A specific polymerase chain reaction (PCR) was developed, which confirmed
      the diagnosis. An in situ PCR demonstrated hamster polyomavirus DNA within
      lymphocytes of the multicentric lymphoma and renal tubular epithelial cells and
      within clusters of enterocytes in the jejunum. These data are consistent with
      environmental dissemination of hamster polyomavirus virions through the renal
      tubular epithelium and into the urine and with fecal shedding of hamster
      polyomavirus virions; however, additional studies will be needed to confirm these
      observations.

PMID- 11467480
TI  - Immunohistochemical evaluation of a malignant phecochromocytoma in a wolfdog.
AB  - A malignant pheochromocytoma with multiple metastases was diagnosed in a 7-year
      old male wolfdog that resulted from a cross between an eastern timber wolf (Canis
      lupus lycaon) and an Alaskan malamute. A yellowish white neoplastic mass
      approximately 10 cm diameter was found in the right adrenal gland. The neoplasm
      penetrated through the wall of the caudal vena cava. A diagnosis of
      pheochromocytoma was established by histopathologic and immunohistochemical
      procedures. Immunohistochemically, the neoplastic cells expressed chromogranin A,
      substance P, synaptophysin, Leu-7, protein gene product 9.5, methionine
      enkephalin, S100 protein, and galanin. Multiple metastatic tumors were found in
      the kidneys, spleen, lungs, heart, and liver.

PMID- 11467481
TI  - Clinical, pathologic, immunohistochemical, and virologic findings of eastern
      equine encephalomyelitis in two horses.
AB  - Natural eastern equine encephalitis alphavirus (EEEV) infection was diagnosed in
      two adult horses with anorexia and colic, changes in sensorium,
      hyperexcitability, and terminal severe depression. Myocardium, tunica muscularis
      of stomach, intestine, urinary bladder, and spleen capsule had coagulative
      necrosis and perivascular lymphocytic infiltrate. Central nervous system (CNS)
      lesions were diffuse polioencephalomyelitis with leptomeningitis characterized by
      perivascular T lymphocyte cuffing, marked gliosis, neuronophagia, and multifocal
      microabscesses. Lesions were more prominent within cerebral cortex, thalamus,
      hypothalamus, and mesencephalon. EEEV was identified in the cytoplasm of cardiac
      myocytes and smooth muscle cells of spleen, stomach, intestine, urinary bladder,
      blood vessels, and dendritic cells. In the CNS, EEEV-positive cells included
      neurons, astrocytes, oligodendrocytes, microglia, and neutrophils. EEEV was
      isolated from the CNS of both horses. The detailed description of the encephalic
      and spinal EEEV localization and the findings of EEEV in extraneural tissues
      contribute to the understanding of this important multisystemic zoonotic disease.

PMID- 11467482
TI  - Invasive phaeohyphomycosis caused by Curvularia species in a dog.
AB  - A 2-year-old female Boxer dog was presented with a history of skin lesions that
      started 1 month after being given oral glucocorticoids for a neurologic problem.
      Clinically, the animal had focal areas of alopecia with papules and nodules often
      with ulceration overlain by crusts. Lesions were most common on the dorsum and
      the lateral aspects of the trunk and extremities. Histologic evaluation revealed
      pigmented fungal organisms within the lumina of hair follicles and throughout the
      dermis and subcutis. These organisms were associated with a multinodular,
      pyogranulomatous luminal folliculitis/furunculosis, dermatitis, and panniculitis.
      Curvularia sp. was isolated from the cutaneous lesions. The histologic
      identification of dematiaceous fungal organisms in the hair follicles may explain
      how phaeohyphomycosis can occur without history of a penetrating injury.

PMID- 11467483
TI  - Disseminated Mycobacterium celatum (type 3) infection in a domestic ferret
      (Mustela putorius furo).
AB  - A 4-year-old male ferret (Mustela putoriusfuro) had a 6-month history of weight
      loss and gradual development of depression and coughing. Necropsy findings
      included pale gray tissue around the distal trachea, multiple nodules in the
      lungs, a single nodule in the stomach wall, gray foci in the liver, and enlarged
      lymph nodes. Histologic examination revealed multifocal to coalescing
      granulomatous inflammation in the trachea, lungs, stomach, liver, and lymph
      nodes, with acid-fast bacteria in epithelioid cells and macrophages. The acid
      fast bacteria were identified as Mycobacterium celatum (type 3) using DNA
      sequence analysis of the 16S ribosomal DNA gene. M. celatum is a recently
      described mycobacterium isolated mainly from immunocompromised humans. This is
      the first report of M. celatum infection in an animal.

PMID- 11467484
TI  - Multicentric lymphoblastic lymphoma in a loggerhead sea turtle (Caretta caretta).
AB  - A juvenile female loggerhead sea turtle (Caretta caretta) stranded in Gran
      Canaria was submitted for necropsy. The turtle had exhibited anorexia and
      lethargy for 2 weeks prior to its death. At necropsy, the thymus was enlarged by
      two white and firm nodules. White nodules similar to those in thymus were
      observed in the plastron, thyroid gland, heart, aorta, left lung, spleen, liver,
      kidneys, stomach, and small intestine. Histopathology revealed a neoplastic
      proliferation of round cells identified as lymphoid cells. Ultrastructurally, the
      neoplastic cells were consistent with lymphoblastic cells, and viruses were not
      detected. The diagnosis was multicentric lymphoblastic lymphoma. This is the
      first report of a lymphoid neoplasm in a sea turtle.

PMID- 11467485
TI  - Atypical membranoproliferative glomerulonephritis in a cat.
AB  - Membranoproliferative glomerulonephritis was observed in a 2-year-old male
      Japanese domestic cat with clinical renal failure. In the glomeruli, moderate
      mesangial hypercellularity with an increased mesangial matrix and thickening of
      the capillary walls were prominent. In addition, frequent duplication of the
      capillary walls, splitting, and spike formation were observed in the glomerular
      basement membrane. Granular cat IgG and complement component deposition were
      detected globally along the glomerular capillary walls and in the mesangium.
      Transmission electron microscopy revealed dense deposits in the subendothelial
      and subepithelial regions and the mesangium. Mesangial interposition was also
      observed. These glomerular lesions are also found in humans with
      membranoproliferative glomerulonephritis type III, which has not been reported in
      animals.

PMID- 11467486
TI  - Spontaneous complex pheochromocytoma in a Fischer 344 rat.
AB  - A spontaneous complex pheochromocytoma was diagnosed in the adrenal gland of an
      aged female Fischer 344 rat. This expansile neoplasm consisted of
      pheochromocytoma and areas of ganglioneuroma. The supporting stroma of both
      neoplastic components contained spindle-shaped cells, which also formed large
      fascicles. Immunohistochemically, pheochromocytoma cells stained for
      synaptophysin and chromogranin, scattered ganglioneuroma cells stained for
      neurofilament protein, and the spindle-shaped stromal cells were positive for S
      100 protein. Special stains demonstrated Nissl substance in the ganglioneuroma
      cells and nerve fibers in the fascicles.

PMID- 11467487
TI  - Pulmonary vasculotropic EHV-1 infection in equids.

PMID- 11467488
TI  - Despite the fact that information on the magnification of a histopathology image
      has no value or purpose, most journals continue to require it.

PMID- 11467489
TI  - The scientific development of maxillofacial surgery in the 20th century and an
      outlook into the future.
AB  - Maxillofacial surgery is a relatively young speciality of medicine and it was not
      established as an organized specialty until the second half of the 20th century.
      At first it was supported by general surgeons with particular interest in this
      field, and also by inspired, extremely talented dentists. During the past few
      years modern techniques have brought decisive progress also in maxillofacial
      surgery, leading to rapid further development of diagnostic and therapeutic
      possibilities. The development of our specialty in the past century is discussed
      on the four main points of our scope, traumatology, orthognathic, cleft and
      tumour surgery. Considering the future prospects of our specialty one should
      realize that in the near future maxillofacial surgery will also be influenced by
      further medical-technical progress in the field of micro-robots, by percutaneous
      endoscopic techniques and by minimal invasive or laser surgery. Basic research
      will also cause a more profound change in our specialty, especially in the field
      of tumour therapy. Molecular biological research shows some good signs, which
      could already be transmitted to the prevention, diagnosis and also the therapy of
      tumours. In the field of tissue transplantation it is no longer utopia that
      autogenous tissue sampling can be almost completely be avoided. By further
      developing 'tissue engineering' it will be possible to cultivate bones as well as
      soft tissue with the aid of gene technology and transplant them into the face
      using relevant carrier substances. Altogether, the complexity of maxillofacial
      surgery in the coming century will increase, necessitating the best and widely
      trained maxillofacial surgeons for successful accomplishment.

PMID- 11467490
TI  - New Zealand Maori family with the pro250arg fibroblast growth factor receptor 3
      mutation associated with craniosynostosis.
AB  - BACKGROUND: A large New Zealand Maori family has non-syndromic coronal
      craniosynostosis, which is inherited as an autosomal dominant mutation with
      variable expression. The aim of the study is to determine whether the family has
      the pro250arg mutation in the gene for fibroblast growth factor receptor 3
      (FGFR3), a mutation found in patients with various types of craniosynostosis.
      PATIENTS: Fourteen members of a New Zealand Maori family were evaluated, of whom
      five have coronal synostosis. A family pedigree tracing six generations was
      recorded. METHODS: Blood samples were drawn for genomic DNA analysis from 14
      family members. Polymerase chain reaction, restriction-enzyme digestion and DNA
      sequencing was performed to identify the pro250arg mutation in FGFR3. RESULTS:
      Seven family members were heterozygous for the pro250arg mutation in FGFR3. The
      mutation showed autosomal dominance with reduced penetrance and variable
      expressivity. CONCLUSION: Our data and those of other investigators suggest that
      we should begin integrating molecular diagnosis with phenotypic diagnosis of
      craniosynostoses.

PMID- 11467491
TI  - Standardized evaluation and documentation of findings in patients with
      craniosynostosis.
AB  - Surgical correction of craniosynostosis is usually performed according to
      standard procedures. However, a standard for clinical examination and report of
      findings for patients with craniosynostosis does not exist as yet. To compare
      findings from different hospitals, a documentation system was developed by a
      national craniosynostosis group. This system comprises a two-page document,
      clinical photographs, radiographs, CT scans, anthropometric measurements and
      molecular genetic findings. Data from craniosynostosis patients collected from
      participating hospitals are stored in a database, which facilitates online
      access. The documentation system was developed in cooperation with the group
      during 3 years since 1996. It was evaluated as being practicable and reliable and
      enables a comparability of findings reported in different hospitals. Molecular
      genetic analysis was found to support the investigation of patients with
      craniosynostosis and should therefore be integrated in the clinical evaluation.

PMID- 11467492
TI  - Surgical correction of scaphocephaly: experiences with a new procedure and follow
      up investigations.
AB  - INTRODUCTION: Simple resection of the sagittal suture and the use of alloplastic
      material or extensive skull resections have long been proven to be unsatisfactory
      in the treatment of sagittal synostosis. In contrast to these experiences, the
      immediate correction of skull shape seems to yield the best results without
      significant morbidity. PATIENTS: Thirty-six scaphocephalic infants with an
      average age of 6.5 (3.5-14) months underwent operation by our craniofacial team
      since 1994. METHODS: Wide resection of the sagittal suture was used in
      combination with a bone-strip resection along the coronal and lambdoid sutures.
      Occasionally partial resection and reshaping of the frontal or occipital bone was
      necessary to correct an extremely bulging skull. The cranial growth and shape was
      monitored by anthropometric skull measurements in the last 20 patients. RESULTS:
      Except in two cases, in which the dura mater was minimally injured
      intraoperatively, no complications occurred in any patient. Craniofacial oedema
      always occurred but disappeared after 72 h. The immediate correction of the skull
      shape was successful in all cases and was completed within 6 months
      postoperatively. There was no iatrogenic bone defect one year after surgery.
      Postoperative skull shape and growth was normal. CONCLUSION: These procedures
      seem to be effective in the treatment of scaphocephalus. Further normalization of
      skull shape is achieved by unrestricted postoperative brain growth.

PMID- 11467493
TI  - Repair of bilateral clefts of lip, alveolus and palate. Part 1: A refined method
      for the lip-adhesion in bilateral cleft lip and palate patients.
AB  - The protruding premaxilla represents the most severe problem in the surgical
      closure of a bilateral cleft lip, alveolus and palate (BCLP). In principle there
      are two methods to overcome this obstacle: (1) preliminary lip adhesion and (2)
      presurgical repositioning with intraoral devices. According to the various
      degrees of premaxillary protrusion, sometimes adhesion alone is sufficient, if
      the surgical technique is unlikely to break down. In this paper a refined
      adhesion method is presented, withstanding traction to the wound margins and
      concomitantly enables lip and nose repairs in a single second operation. For
      patients with severe premaxillary protrusion, presurgical use of a Latham
      appliance achieves conditions for safe lip adhesion as above. Both treatment
      methods are outlined.

PMID- 11467494
TI  - Repair of bilateral clefts of lip, alveolus and palate. Part 2: Concomitant lip
      closure and columella lengthening after lip adhesion.
AB  - Lip repair and synchronous columella lengthening in bilateral clefts of the lip,
      alveolus and palate following lip adhesion according to the method outlined in
      Part 1 is described in this part of the paper. Together with lip and nose repair
      the gingivo-periosteoplasty can also be performed when the alveolar process is
      perfectly aligned and the greater and lesser segments abutt onto each other.

PMID- 11467495
TI  - Repair of bilateral cleft lip, alveolus and palate. Part 3: Follow-up criteria
      and late results.
AB  - The last part of this series outlines closure of the hard palate with various
      modifications depending on the remaining width of the cleft. Additionally the
      necessity and parameters of follow-up documentation are emphasized and detailed.
      For the two patients shown in Parts 1 and 2, the corresponding data are given.
      Accumulated facial growth curves of all the other patients treated the same way
      are also given. The main results are: (A) lip and nose can be reconstructed much
      more easily after repositioning of the premaxilla and (B) the reported anterior
      growth delay following use of the Latham appliance could not be confirmed during
      the ongoing follow-up.

PMID- 11467496
TI  - Experimental microsurgery of salivary ducts in dogs.
AB  - The results achieved by experimental microsurgical suturing of salivary ducts in
      dogs are presented. Nine partial lesions and one complete transection of the
      ducts were made on parotid and submandibular ducts. Four to seven interrupted
      microsutures were used for each lesion. The operations were successful in seven
      out of 10 cases, as observed by sialography. Histologically, granulation tissue
      compressing the ducts was observed after suturing the lesions. Four venous graft
      transplantations were performed and none were successful. After venous graft
      transplantation, the transplant was not apparent histologically, raising doubt as
      to the potential success of this technique. The use of stenting is discussed
      based on a summary of the published literature. Those reports indicate that long
      term stenting can benefit the outcome of salivary duct repair. The use of dogs as
      a model for experimental salivary duct operations has been shown to be valuable
      in assessing various surgical techniques.

PMID- 11467497
TI  - Memory impairment induced by cholinergic antagonists injected into the mushroom
      bodies of the honeybee.
AB  - The role of honeybee central brain structures, suspected to be cholinergic, has
      been studied in learning and memory. The nicotinic antagonist mecamylamine and
      the muscarinic antagonist scopolamine were locally injected into the calyces and
      the alpha-lobes of mushroom bodies, and their effects on memory acquisition and
      retrieval were investigated using one-trial olfactory conditioning of the
      proboscis extension reflex. A strong impairment of the olfactory learning was
      noticed following mecamylamine injection into the mushroom body calyces.
      Mecamylamine and scopolamine disturbed retrieval processes when injected into the
      alpha-lobes of mushroom bodies but remain without effect on these processes when
      injected into the mushroom body calyces. These results emphasise the role of the
      cholinergic networks of the mushroom bodies in the formation and recall of memory
      in the honeybee. They suggest that the role of the brain structures in these
      processes is sequential. Mushroom body calyces involved in the associative
      process of olfactory learning could be relayed by the alpha-lobes for information
      retrieval.

PMID- 11467498
TI  - Song pattern recognition in the grasshopper Chorthippus biguttulus: the mechanism
      of syllable onset and offset detection.
AB  - The male song of the duetting grasshopper Chorthippus biguttulus consists of
      syllables alternating with noisy pauses. The syllable-pause structure is
      important for song recognition by the female. Using playback experiments we
      investigated the mechanism by which intensity modulations within the song pattern
      are used to detect syllable onsets and offsets. We varied the relative onset
      level (level of the syllable beginning relative to the noisy pause) and the
      relative offset level (level of the noisy pause relative to the syllable end)
      independently in different experiments. For all females, an increase in intensity
      defining the syllable onset was necessary to evoke responses. Syllable offset
      cues were not always necessary: some females responded to continuous noise
      stimuli wherein only syllable onsets were marked by short pulses of high
      intensity. Those females that did not require syllable offset cues did not,
      however, lack a functional pause detection mechanism, since their responses to
      model songs containing silent pauses were restricted to a given range of pause
      durations. We propose that syllable-pause detection involves two independent
      processes: (1) syllable onset detection by a phasic neuronal unit that can be re
      activated only after a short pause, and (2) the rejection of unacceptably long
      pauses by a second unit.

PMID- 11467499
TI  - Hearing in reindeer (Rangifer tarandus).
AB  - The audiogram of two yearling male reindeer (Rangifer tarandus tarandus) were
      determined using a conditioned suppression/avoidance procedure. During testing,
      the animal was drinking from a metal bowl while pure tone signals were played at
      random intervals and followed by an electric shock in the bowl. By breaking
      contact with the bowl at sound signals, the animal avoided the shock. The animals
      detected sounds at intensities of 60 dB or less from 70 Hz to 38 kHz. The
      frequency range of best sensitivity was relatively flat from 1 kHz to 16 kHz,
      with a best sensitivity of 3 dB at 8 kHz. The hearing ability of reindeer is
      similar to the hearing ability of other ungulates.

PMID- 11467500
TI  - Peripheral encoding of behaviorally relevant acoustic signals in a vocal fish:
      harmonic and beat stimuli.
AB  - Nesting male midshipman fish, Porichthys notatus, emit simple, long-duration
      sounds known as hums, which are attractive to gravid females. While hums share
      the multi-harmonic structure typical of many vertebrate communication sounds,
      their lack of amplitude modulation gives individual hums unusually simple
      temporal envelopes. However, hums often overlap, producing beats in the summed
      acoustic waveform. This study presents responses of individual saccular afferent
      fibers to two-tone harmonic and beat stimuli presented via an underwater
      loudspeaker. Spike activity was quantified as vector strength of synchronization
      and average spike rate. Responses to harmonic stimuli depended on harmonic phase;
      these effects apparently resulted primarily from variation in waveform fine
      temporal structure rather than auditory non-linearities. At most phases, addition
      of the harmonic enhanced afferent synchronization compared to the fundamental
      alone. Two-tone beat stimuli evoked stronger synchronization to the component
      frequencies than to the beat modulation rate. Vector strength tended to be higher
      to the lower frequency component, and this pattern appeared to derive from
      afferent tuning. Midshipman saccular afferents encoded both the temporal envelope
      and waveform fine structure of these naturalistic signals, information that may
      be important in conspecific communication.

PMID- 11467501
TI  - Frequency discrimination threshold at search call frequencies in the echolocating
      bat, Eptesicus fuscus.
AB  - While searching for prey in open spaces, Epteisicus fuscus emits long-duration,
      downward frequency-modulated calls which cover a frequency band of about 28-22
      kHz. In the ascending auditory pathways of E. fuscus, neurons tuned to these
      search call frequencies are characterised by a remarkably high frequency
      selectivity and very sensitive absolute thresholds. We investigated whether this
      narrow tuning is reflected in an exceptional psychoacoustic frequency
      discrimination ability. The average frequency difference limen of E. fuscus at
      search call frequencies determined in a two-alternative, forced-choice experiment
      amounted to about 420 Hz, corresponding to a Weber ratio of 0.017. This value is
      similar to those found in non-echolocating mammals, and an order of magnitude
      larger than the frequency difference limens of bats emitting constant-frequency
      call components. We discuss these differences in frequency difference limen, and
      relate them to different echolocation strategies.

PMID- 11467502
TI  - Modulation of sucrose response thresholds in honey bees (Apis mellifera L.):
      influence of genotype, feeding, and foraging experience.
AB  - The perception of sugar is important to honey bees for making foraging decisions.
      We measured bees' perception by determining what concentration of sucrose touched
      to the antennae elicited the proboscis extension response (response threshold). A
      low response threshold (extension at low concentration) suggests a high
      perceptual value of sucrose. and vice versa. Perception of sucrose solutions
      differed between two artificially selected genotypic strains and was modulated by
      the bees' recent feeding experiences. Bees offered 10%, 30%, or 50% sucrose
      solutions in small cages overnight, and in large flight-cages or free-flying in
      the field for several days, had subsequent response thresholds positively
      correlated to the concentration offered. Empty bees, whether they were nectar,
      water or pollen foragers, dancers or non-dancers, had a significantly lower
      threshold than loaded bees. Crop volume affected response thresholds directly and
      independently of sucrose concentration. We interpret these findings as multiple
      mechanisms that operate in different time scales, modulating perception of
      sucrose. Changes occurred in the time scale of evolutionary processes as
      demonstrated by genotypic differences. Changes with foraging experience occur in
      hours or minutes while effects of crop filling are instantaneous.

PMID- 11467503
TI  - Arthropod touch reception: spider hair sensilla as rapid touch detectors.
AB  - Wandering spiders like Cupiennius salei are densely covered by tactile hairs. In
      darkness Cupiennius uses its front legs as tactile feelers. We selected easily
      identifiable hairs on the tarsus and metatarsus which are stimulated during this
      behavior to study tactile hair properties. Both the mechanical and
      electrophysiological hair properties are largely independent of the direction of
      hair displacement. Restoring torques measure 10(-9) to 10(-8) Nm. The torsional
      restoring constant S changes non-linearly with deflection angle. It is of the
      order of 10(-8) Nm/rad, which is about 10,000 times larger than for
      trichobothria. Angular thresholds for the generation of action potentials are
      ca.1 degrees. Electrophysiology reveals a slow and a fast sensory cell, differing
      in adaptation time. Both cells are movement detectors mainly responding to the
      dynamic phase (velocity) of a stimulus. When applying behaviorally relevant
      stimulus velocities (up to 11 cm s(-1)) threshold deflection for the elicitation
      of action potentials and maximum response frequency are reached as early as 1.2
      ms after stimulus onset and followed by a rapid decline of impulse frequency.
      Obviously these hairs inform the spider on the mere presence of a stimulus but
      not on details of its time-course and spatial orientation.

PMID- 11467504
TI  - Arthropod touch reception: stimulus transformation and finite element model of
      spider tactile hairs.
AB  - Striving towards an in depth understanding of stimulus transformation in
      arthropod tactile hairs, we studied the mechanical events associated with tactile
      stimulation. A finite element model was developed taking a tarsal tactile hair of
      the spider Cupiennius salei as an example. Considering hair diameter, wall
      thickness, and curvature, the hair is subdivided into six regions each with its
      specific mechanical properties. When the hair is touched from above with a flat
      surface oriented parallel to the tarsus the point of stimulus contact moves
      towards the hair base with increasing load and hair deflection. Thereby the
      effective lever arm is reduced protecting the hair against breaking near its
      base. At the same time the mechanical working range of the hair increases
      implying higher mechanical sensitivity for small deflections (about 5x10(-5)
      N/degrees) than for large deflections (about 1x10(-4) N/degrees). The major
      stresses within the hair shaft are axial stresses due to bending. The position of
      stress maxima moves along the shaft with the movement of the stimulus contact
      point. Remarkably, the amplitude of this maximum (about 1x10(5) N/m2) hardly
      changes with increasing loading force due to the way the hair shaft is deflected
      by the stimulus.

PMID- 11467505
TI  - Effect of culture system on the yield and quality of bovine blastocysts as
      assessed by survival after vitrification.
AB  - The aim of this study was to assess the effect of a bovine in vitro culture
      system on blastocyst yield and quality after vitrification. In Experiment 1,
      IVM/IVF zygotes were cultured in either synthetic oviduct fluid (SOF) in 5% CO2,
      5% O2, 90% N2; or TCM199-granulosa cells (TCM199-GCM) in 5% CO2 in air. In vivo
      blastocysts were used as a control. Culture in SOF resulted in a significantly
      higher blastocyst yield on both Day 7 (31.3 vs 13.2%, P < 0.001) and 8 (36.8 vs
      23.7%, P < 0.001) than did culture in TCM199-GCM. After vitrification, survival
      at 72 h of in vivo blastocysts was significantly higher than both in vitro
      groups, while significantly more blastocysts produced in TCM199-GCM survived
      compared to those produced in SOF (0, 43.5, 78.3% for SOF, TCM199-GCM and in
      vivo, respectively P < 0.01). In Experiment 2, SOF-GCM proved to be the best post
      warming culture system of those tested and was adopted as the post-warming medium
      for all subsequent experiments. In Experiment 3, zygotes were cultured in SOF or
      SOF-GCM, in either 5% CO2 in air, or 5% CO2, 5% O2, 90% N2. In agreement with
      Experiment 1, culture in SOF in 5% O2 resulted in significantly more blastocysts
      at Day 7 (26.4 vs 17.3%, P < 0.01) and Day 8 (31.5 vs 23.2%, P < 0.01) than did
      culture in SOF-GCM. However, survival at 72 h post vitrification was
      significantly higher for SOF-GCM (44 vs 8.3%, P < 0.001). Increasing the O2
      concentration to 20% significantly reduced the blastocyst eld from SOF (31.5 vs
      17.3%, P < 0.001). In addition, the quality of blastocyst produced was reduced in
      terms of survival post vitrification (8.3 vs 0%, P < 0.05). In contrast, there
      was no difference in blastocyst yield (23.2 vs 25.2%) or survival (44.0 vs 36.9%)
      in SOF-GCM, irrespective of O2 concentration. Experiment 4 examined the duration
      of exposure to GCM necessary to acquire improved blastocyst quality. Zygotes were
      cultured in SOF; SOF until Day 3, followed by SOF-GCM for the remainder of the
      culture; SOF until Day 5, followed by SOF-GCM for the remainder of the culture;
      or SOF-GCM for the entire culture. Survival at 72 h post vitrification was
      significantly higher (P < 0.05) in Groups 2 (50.0%, 13/26) and 4 (55.3%, 26/47)
      than in Groups 1 (21.7%, 10/46) and 3 (10.8%, 4/37). In conclusion, culture
      system can affect blastocyst yield and quality and crytolerance is a useful
      indicator of blastocyst quality.

PMID- 11467506
TI  - Breeding ewes out-of-season using melengestrol acetate, one injection of
      progesterone, or a controlled internal drug releasing device.
AB  - A series of studies was designed to identify methods of improving out-of-season
      breeding success in ewes. In Experiment 1, 190 mature ewes were assigned to
      receive in April, either: (A) a control ration of 0.3 kg corn twice daily for 8 d
      before ram introduction (control ewes n=49), (B) the control ration containing
      0.125 mg of melengestrol acetate (MGA) in 0.3 kg corn (MGA8a ewes n=46), (C) the
      control ration or 7.5 d followed by 1 feeding of 0.5 mg MGA in 0.3 kg corn (MGA1
      ewes n=48), or (D) the control ration plus a 20 mg i.m. injection of progesterone
      on D 8 (P ewes n=47). Ewes were exposed to rams for 21 d. A greater percentage of
      MGA8a and P ewes lambed than did control ewes (P < 0.04). The lambing rate was
      greatest among MGA8a (P < 0.02 vs. control), intermediate among P ewes (P < 0.19
      vs. control) and least among MGA1 and control ewes (P > 0.79). In Experiment 2,
      70 mature ewes were assigned to receive in June, either: (A) a control ration of
      0.3 kg of corn twice daily for 8 d before to ram introduction (control ewes
      n=25), (B) the control ration containing 0.125 mg of MGA per 0.3 kg corn (MGA8b
      ewes n=21), or (C) the control ration and simultaneous treatment of ewes with a
      progesterone-containing controlled internal-drug releasing device (CIDR ewes
      n=24). Ewes were exposed to rams for 21 d. Both CIDR and MGA8b ewes exhibited
      estrus earlier than did control ewes (P < 0.01). The CIDR ewes exhibited estrus
      earlier than did the MGA8b ewes (P < 0.05). A greater percentage of ewes treated
      with CIDR or MGA8b lambed than did control ewes (P < 0.01), with more CIDR ewes
      lambing than MGA8b ewes (P < 0.01). The lambing rate was greater in CIDR ewes
      than in control ewes (P < 0.04). These data provide evidence that several options
      exist to improve pregnancy success in ewes bred out of season and that success
      varies with method of treatment.

PMID- 11467507
TI  - Metabolic cues for puberty onset in free grazing Holstein heifers naturally
      infected with nematodes.
AB  - Leptin is a new plausible candidate for the molecular link between nutritional
      status and the reproductive axis. In previous studies we described that
      continuous natural nematode infections in heifers retarded growth and delayed the
      onset of puberty, and that the insulin-like growth factor I (IGF-I) was involved.
      In the present study we monitored the leptin levels during development in heifers
      naturally parasitized versus those chronically treated with ivermectin and we
      investigated whether growth hormone (GH) accounted for the differences in IGF-I
      previously noted. Insulin levels were also measured. Prolactin hormone was
      recorded as an indicator of immune system activation. We found a direct
      correlation between leptin and body weight during development and a prepubertal
      surge of the hormone 2 weeks before the first progesterone peak that indicates
      the onset of puberty. This suggests that leptin may act as a signal for this
      event. Insulin did not vary during growth and prepuberty. On the other hand, GH
      as not responsible for diminished IGF-I levels in parasitized animals as levels
      were similar in both groups. The GH levels were high at birth and then diminished
      rapidly and remained constant during development and puberty. The last hormone
      studied, prolactin, followed seasonal changes of sunlight duration and presented
      sporadic bursts in infected animals. These were related to high nematode
      infection and are probably involved in the immune response of the host.

PMID- 11467508
TI  - Effect of insemination time of frozen semen on incidence of uterine fluid in
      mares.
AB  - Ninety five mares were inseminated with frozen semen either within 12 h before
      ovulation or within 8 h after ovulation. The effect of preovulatory versus
      postovulatory insemination (AI) on the subsequent detection of uterine fluid was
      studied. The overall pregnancy rate was 43% and this was not significantly
      influenced by preovulatory or postovulatory insemination. When mares were first
      examined 12 h after AI, 18 of 52 mares (35%) had accumulated uterine fluid.
      However, when mares were first examined 18 to 24 h after AI, only 6 of 43 mares
      (14%) had uterine fluid. Presence of intrauterine fluid significantly lowered
      pregnancy rates. Timing of insemination did not affect incidence of uterine
      fluid. Serum concentrations of estrogen and progesterone at time of insemination
      did not influence uterine clearance or pregnancy rates, but both hormones were
      higher at preovulatory than at postovulatory inseminations. We concluded that
      there was no evidence that postovulatory inseminations would predispose mares to
      persistence of uterine fluid after AI.

PMID- 11467509
TI  - Content of meiosis activating sterols in equine follicular fluids: correlation to
      follicular size and dominance.
AB  - Meiosis activating sterols (MAS) are pre-cholesterol sterols that can be isolated
      from follicular fluid (FF-MAS) or testes (T-MAS). Meiosis activating sterols
      trigger the resumption of meiosis in cultured meiotically competent oocytes. In
      the present work MAS, cholesterol and progesterone were assayed by HPLC in
      follicular fluids collected from pony mares at fixed days after the last
      ovulation. Follicles were divided into two groups according to whether they were
      aspirated before or after Day 17 after the last ovulation. The latter group was
      further divided according to whether the follicle diameter was < or = 22 mm or >
      27 mm. Both FF-MAS and T-MAS were detected in almost all samples. Overall, the
      total amount of MAS in the follicular fluids increased with the size of the
      follicles but was accompanied by a decrease in the amount of free cholesterol.
      The amounts of MAS and progesterone in > 27 mm follicles aspirated after Day 17
      were significantly higher as compared to the other groups. A transversal cohort
      analysis showed that the largest follicle at the time of aspiration had the
      highest level of MAS after day 17 of the cycle, which was not always true for
      follicle samples aspirated before Day 17 of the cycle. The study demonstrates
      that the content of MAS in equine follicular fluids increased during follicular
      maturation concomitant with a decrease in the concentration of free cholesterol.
      Moreover, MAS concentration is higher in dominant follicles than in subordinate
      follicles. The MAS may therefore play an as yet unknown physiological role during
      pre-ovulatory maturation.

PMID- 11467510
TI  - The repeatability of superovulatory response and embryo recovery in sheep.
AB  - Over an 8-year period, a total of 328 Scottish Blackface donor ewes were involved
      in a MOET program. They were synchronized with fluorogestone acetate sponges and
      superovulated with ovine FSH. After the onset of estrus, ewes were hand-mated and
      laparoscopic artificial insemination was performed with fresh semen 44-46 h after
      sponge removal. Embryos were recovered semi-laparoscopically on either Day 5 or
      Day 6 after insemination. Of the 328 donor ewes used, 222 ewes were supervoulated
      only once, while the remaining ewes were superovulated either twice (73 ewes), 3
      times (26 ewes) or 4 times (7 ewes) at yearly intervals to generate a maximum of
      474 records for subsequent analysis. There was no significant change in either
      mean ovulation rate or the mean number of embryos recovered per donor ewe at
      successive treatments. However, significant (P < 0.05 at least) effects of both
      year and donor ewe age existed for superovulatory response and number of embryos
      recovered, though only the effect of year was significant (P < 0.001) for
      percentage embryo recovery. Repeatability was significant (P < 0.05 at least) for
      both superovulatory response (r = 0.55, s.e. 0.055) and number of embryos
      recovered (r = 0.38, SE 0.074), but not for percentage embryo recovery (r = 0.04,
      SE 0.102).

PMID- 11467511
TI  - Does CO2 enhance short-term storage success of Chinook salmon (Oncorhynchus
      tshawytscha) milt?
AB  - Successful short-term storage of salmonid milt depends on numerous factors,
      including temperature, fluid volume, and gaseous environment, with storage at low
      temperatures under an atmosphere of 100% O2 being the most common method.
      Salmonid sperm maintained in a storage environment with elevated carbon dioxide
      (CO2) levels, such as the approximately 4% CO2 in exhaled air, are not motile
      when activated. While these modest levels of CO2 inhibit sperm motility, the
      effect is reversible within hours after exposure to a CO2-free oxygenated
      environment. Therefore, the effect of CO2 (as a component gas in the storage
      environment) on chinook salmon (Oncorhynchus tshawytscha) sperm motility and
      viability was examined. The hypothesis of the current investigation was that CO2
      exposure with subsequent CO2 removal would be beneficial during short-term
      chinook salmon milt storage. Milt samples were collected from mature (adult) and
      precocious (jack) male chinook salmon and stored under various CO2 and O2 levels
      at 3 to 4 degrees C for up to 14 days. Milt samples were then removed from the
      incubation environments and maintained under CO2-free humidified air with
      continuous mixing for 4 h at 10 degrees C before analysis of motility. The
      resultant motility of samples incubated under 3.5% or less CO2 was not different
      than controls during the 14 d incubation period; motility of samples stored under
      higher CO2 tensions were significantly lower. The motility of samples incubated
      under 3.5% CO2 reached the maximum recovered motility after 2 h exposure to CO2
      free humidified air, while the motility of sperm incubated under 13.4% CO2 levels
      recovered no motility even after 6 h exposure to CO2-free humidified air. The
      motility of samples incubated under normoxia was significantly greater than that
      of samples incubated under hyperoxia (approximately 90% O2) at both 7 and 14 d,
      regardless of the CO2 level. Sperm viability was relatively unaltered by any of
      the incubation conditions examined. The results of this investigation suggest
      that there is no apparent advantage to storage of chinook salmon sperm in the
      presence of CO2 and that storage under hyperoxia negatively affects sperm
      function compared to storage under normoxia.

PMID- 11467512
TI  - Transcriptional activity in in vivo developed early cleavage stage bovine
      embryos.
AB  - Bovine embryos developed in vivo from the first to the fourth post-fertilization
      cell cycles were processed for ultrastructural autoradiography after incubation
      with 3H-uridine for 10 h. We wished to detect and localize transcriptional
      activity. During the first (1-cell stage) and second (2-cell stage) cell cycles
      we observed electron-dense fibrillar spheres (nucleolus precursor bodies) and
      fibrillo-granular complexes in the nuclei. During these cell cycles,
      autoradiographic labeling was observed in heterochromatic areas and at the
      periphery of the fibrillo-granular complexes. During the third cell cycle (4-cell
      stage) the electron dense fibrillar spheres exhibited vacuolization.
      Autoradiographic labeling was found in heterochromatic areas and in the vacuoles
      of the fibrillar spheres. During the fourth cell cycle (8-cell stage), the
      electron dense fibrillar spheres exhibited both a large eccentric vacuole and
      peripheral smaller vacuoles. Autoradiographic labeling was found in
      heterochromatic areas throughout the nucleus and over the substance of the
      vacuolated fibrillar spheres, especially where chromatin penetrated into them and
      where presumptive fibrillar centers were formed. In conclusion, a low level of
      transcription can be detected in in vivo developed bovine embryos as early as the
      one-cell stage. Moreover, nuclear entities that probably prepare for nucleolus
      formation during the fourth cell cycle, display a progressive autoradiographic
      labeling that signals a possible initiation of transcription of the ribosomal RNA
      genes during the third cell cycle.

PMID- 11467513
TI  - Meiotic and developmental competence of prepubertal and adult swine oocytes.
AB  - The present study was conducted to compare meiotic and cytoplasmic competence of
      prepubertal and adult porcine oocytes, and the effects of EGF (0 to 100 ng/mL),
      FSH (0 to 400 ng/mL) and prepubertal pFF (0 to 10%) on nuclear maturation.
      Prepubertal oocytes were less responsive to FSH and pFF than were adult oocytes
      in terms of stimulation of nuclear maturation. The best nuclear maturation rates
      for prepubertal oocytes were obtained with 10 ng/mL EGF and 400 ng/mL FSH,
      whereas for adult oocytes no additional effect of EGF was seen in the presence of
      400 ng/mL FSH. Supplementation with pFF had no additional effect on MII yield
      over that obtained with EGF plus FSH. After maturation in the presence of EGF,
      FSH and cysteamine, fertilization rates were not different between adult and
      prepubertal oocytes, but polyspermy was more frequent in prepubertal oocytes (31
      +/- 17% vs. 17 +/- 7% in prepubertal and adult oocytes, respectively, P < 0.05).
      The addition of pFF to maturation medium decreased oocyte fertilization of adult
      oocytes and polyspermic fertilization in prepubertal oocytes. Blastocyst yield
      and developmental competence were significantly reduced in prepubertal oocytes
      compared to adult oocytes. The mean cell numbers in blastocysts cultured for 7
      days ranged from 61 to 74, and did not differ among groups. Finally, the
      viability of the 2- to 4-cell embryos and blastocysts produced was assessed by
      embryo transfer experiments. One offspring was obtained after transfer of 2- to 4
      cell embryos, and one after transfer of in vitro-produced blastocysts. In
      conclusion, although prepubertal gilt oocytes appeared less meiotically and
      developmentally competent than their adult counterparts, they can be used to
      produce blastocysts able to develop to term.

PMID- 11467514
TI  - Effect of extender composition and equilibration time on fertilization ability
      and enzymatic activity of rainbow trout cryopreserved spermatozoa.
AB  - The effects of extender composition and equilibration time on fertilizing ability
      of cryopreserved spermatozoa from rainbow trout, Oncorhynchus mykiss, were
      investigated. In addition, enzyme activity in supernatants from thawed sperm was
      assessed. The use of the two extenders: Erdahl & Graham's + 10% DMA (dimethyl
      acetamide) + 10% egg yolk and 0.3 M glucose + 10% DMA yielded the highest post
      thaw fertilization rates. We observed interactions between extender constituents
      and the equilibration of diluted semen. This indicates a multifactorial effect of
      the extender constituents on spermatozoal resistance against injuries. The 10-min
      equilibration of spermatozoa in extender before freezing generally lowered the
      fertilization ability of spermatozoa, except for DMA-based extenders. The
      addition of egg yolk to the extender was generally beneficial, especially in DMA-
      and DMSO-based extenders. The use of low-density lipoprotein fraction showed no
      advantage to full-yolk or free-of-yolk extenders. Aspartate aminotransferase and
      lactate dehydrogenase leakage from damaged spermatozoa correlated negatively with
      the ability of cryopreserved spermatozoa to fertilize eggs. Each factor tested,
      when analyzed separately, did not give general information about its effect on
      the fertilization ability of cryopreserved sperm. The multifactorial analysis of
      the important factors in cryopreservation of trout spermatozoa showed their
      cumulative effect. This is the most likely reason for divergent information
      reported elsewhere on the effect of various factors in the cryopreservation of
      rainbow trout spermatozoa.

PMID- 11467515
TI  - Plasma and pituitary concentrations of gonadotrophins (FSH and LH) in minke
      whales (Balaenoptera acutorostrata) during the feeding season.

PMID- 11467516
TI  - Seminal plasma addition attenuates the dilution effect in bovine sperm.
AB  - Dilution of semen to low cell numbers/dose can result in a bull-dependent
      reduction in the post-thaw viability of cryopreserved bovine spermatozoa. It is
      possible that essential seminal plasma components are lacking at the greater
      dilution rates, thereby contributing to the deleterious effects of semen
      dilution. Ejaculates of 6 Holstein bulls were diluted to 120 x 10(6) sperm/mL in
      an egg yolk citrate extender (EYC). Split samples were further diluted to 80, 40,
      20 and 4 x 10(6) sperm/mL in EYC extender with (+SP) and without (-SP) the
      addition of frozen/thawed seminal plasma previously obtained from a vasectomized
      bull. Serial dilutions for the +SP treatments were calculated and performed such
      that each dilution contained a volume of seminal plasma equal to the original 120
      x 10(6) sperm/mL dilution. Samples were then loaded into 0.5-mL French straws
      yielding final sperm concentrations of 30, 20, 10, 5 and 1 x 10(6)/dose. Straws
      from each dilution were analyzed using 2 stain combinations: the sperm viability
      stain, SYBR-14 and propidium iodide (PI); or the mitochondrial-specific, membrane
      potential-dependent stain JC-1 along with PI. Split-plot analysis of variance
      indicated that within bulls, there were greater proportions of viable spermatozoa
      in aliquots containing added seminal plasma than in aliquots without added
      seminal plasma (P < 0.05). Contrast analyses showed that sperm viability
      significantly decreased as sperm concentration decreased in the -SP samples.
      Although the dilution effect was also observed in the +SP samples, the magnitude
      of the effect was less than in the -SP samples. At most sperm concentrations, the
      proportions of spermatozoa that stained with JC-1 were correlated (r > 0.84; P <
      0.05) with the percentages of SYBR- 14 stained spermatozoa. Furthermore, the
      proportions of JC-1-stained spermatozoa were greater in the +SP aliquots than in
      the -SP samples at a concentration of 10 x 10(6) sperm/0.5 mL. These results
      suggest that the addition of seminal plasma can be beneficial to sperm viability
      when semen is diluted to low cell numbers/dose.

PMID- 11467517
TI  - Chemical properties of bovine cervical mucus during normal estrus and estrus
      induced by progesterone and/or PGF2alpha.
AB  - Ninety-two Friesian cows were used to determine the chemical properties of
      cervical mucus during normal estrus and estrus induced by progesterone (P4)
      releasing intravaginal devices (PRID) and/or prostaglandin F2alpha. The animals
      were assigned to 4 groups (no treatment, a PRID for 12 days plus injection of
      1000 IU PMSG at the removal of PRID, a double i.m. injection of PGF2alpha 11 days
      apart, or PRID for 7 days plus an im injection of PGF2alpha 24 h before the
      removal of PRID). A number of cows with normal estrus exhibited three consecutive
      estrous cycles after delivery. Cows that had not shown estrus for 3 months after
      delivery had their ovaries palpated twice at 10-day intervals, to determine their
      ovarian activity. Then PRID and/or PGF2alpha was administered in cows that had a
      palpable corpus luteum in one of the two palpations (cyclic cows). A double
      artificial insemination (AI) was performed to the cows of the three induced
      estrus groups, while the cows with normal estrus received only one AI. Cervical
      mucus samples were collected from all cows 5 to 30 min before the first AI.
      Additionally, samples of cervical mucus were collected from 20 cows during their
      first estrus after the induced one. The results are summarized as follows: 1) The
      biochemical properties of cervical mucus in the first three estrus periods after
      delivery were similar. 2) These properties were similar both in normal estrus
      after delivery and in the first estrus after an induced one. 3) Glucose and
      fructose concentrations for normal estrus were similar to those for induced
      estrus groups. 4) Total protein and cholesterol concentrations were significantly
      lower (P < 0.001) in normal than in induced estrus, while no difference was found
      among the induced estrus groups. 5) Pregnancy rates of the cows did not differ
      significantly among the normal and the induced-estrus groups. 6) The percentages
      of cows in the induced-estrus groups that produced cervical mucus with total
      protein and cholesterol concentrations similar to those for the normal estrus
      groups was very low.

PMID- 11467518
TI  - Effects of follicle stimulating hormone (FSH) on follicular development, oocyte
      retrieval, and in vitro fertilization (IVF) in ewes during breeding season and
      seasonal anestrus.
AB  - Administration of FSH increases the number of developing follicles, and affects
      oocyte health and cleavage rate. To determine the optimal level of FSH treatment,
      studies were conducted during the normal breeding season and seasonal anestrus.
      In Experiment 1, ewes were implanted with SyncroMate-B (SMB; norgestomet) for 14
      days during the breeding season. Beginning on day 12 or 13 after SMB
      implantation, ewes were treated with saline (control; n=10), or treated with FSH
      for two days (2D; n=9) or three days (3D; n=10). In Experiment 2, conducted
      during seasonal anestrus, ewes were implanted with SMB for 14 days (n=23) or were
      not implanted (n=26). The SMB-implanted and nonimplanted ewes were assigned to
      one of three treatments as in Experiment 1: control (n=13), 2D (n=21) or 3D
      (n=15). In Experiments 1 and 2, ewes were laparotomized to count the number of
      follicles < or = 3 mm and > 3 mm and to retrieve oocytes. Healthy oocytes from
      each treatment were used for IVF. In Experiment 3, ewes (n=6) were implanted
      twice with SMB for 14 days during seasonal anestrus. Ewes were injected with FSH
      for 2 days, and the oocytes were collected and fertilized as in Experiments 1 and
      2. In Experiment 1, FSH-treatment increased (P < 0.05) the number of follicles >
      3 mm, the number of oocytes retrieved from follicles < or = 3 mm and > 3 mm, the
      proportion of healthy oocytes, and the number of oocytes used for IVF. Oocytes
      from control and 2D ewes had greater (P < 0.01) cleavage rates than 3D ewes (68%
      and 71% vs. 42%). In Experiment 2, implanted and nonimplanted ewes had similar (P
      > 0.05) numbers of follicles, total oocytes, and healthy oocytes; therefore, data
      were combined. The FSH treatment increased (P < 0.01) the number of follicles > 3
      mm, and the number of oocytes recovered from follicles > 3 mm. The recovery rate
      of oocytes and the percentage of healthy oocytes were similar for control and FSH
      treated ewes. The cleavage rate in Experiment 2 ranged from 4 to 16%. In
      Experiment 3, the cleavage rate for ewes treated twice with SMB was 27% which
      tended to be greater (P < 0.07) than for the 2D ewes that received one SMB
      implant in Experiment 2. These data indicate that FSH increased the number of
      developing follicles and the number of healthy oocytes retrieved from ewes during
      the breeding season and seasonal anestrus. However, cleavage rates during
      seasonal anestrus were lower than during the normal breeding season in both FSH
      treated and control ewes. Treatment of ewes for 2 days with FSH resulted in a
      greater cleavage rate than treatment of ewes for 3 days.

PMID- 11467519
TI  - Superovulatory response, embryo quality and fertility after treatment with
      different gonadotrophins in native cattle.
AB  - We studied native Mertolengo cattle to evaluate superovulatory (SOV) treatments,
      subsequent fertility of donors and pregnancy rate of recovered embryos. In
      Experiment 1 we compared superovulatory response (SR), embryo quality and plasma
      progesterone (P4) levels between donors treated with eCG (10 cows and 5 heifers)
      vs. FSH (pure, FSH-1, n=10 cows and crude, FSH-2, n=10 cows), during
      progestagenic impregnation. We also compared fertilization rates and embryo
      quality of bred and inseminated eCG and FSH-1 donors. Significantly more viable
      embryos were yielded by FSH than by eCG treated donors. Less FSH-1 than FSH-2
      treated donors showed SR, but the response was identical in responder donors of
      both groups. Fertilization rates were significantly higher in bred than in
      inseminated donors. Plasma P4 levels were only significantly different (higher)
      between responder and non-responder donors on the day of embryo recovery.
      Experiment 2 compared FSH treatments (FSH-2, crude, n=11 cows and FSH-3, pure,
      n=10 cows) started at the midluteal phase. The mean number of viable embryos was
      significantly higher in FSH-3 than in FSH-2 treated donors. Both FSH treatments
      exerted a similar luteotrophic effect upon injection. The FSH-2 donors treated
      during the midluteal phase yielded more ova and showed significantly higher
      plasma P4 levels at all sampling days than those treated during progestagenic
      impregnation. The pregnancy rates of recipient cows were 67% and 46% for fresh
      and frozen-thawed embryos respectively. In Experiment 3, the fertility of donors
      (n=20) after SOV treatments was compared with that of untreated cows (n=40). Time
      to conception of donors, after mating with a bull 14 days after embryo recovery,
      was identical to that of control cows. There was some delay to conception in eCG
      treated cows, but the difference was not significant. These preliminary results
      suggest that response to SOV treatments in Mertolengo cattle might be affected by
      the type of gonadotrophin and by the treatment protocol. The fertility of a
      traditional breeding season after SOV treatments was not impaired. Cryopreserved
      embryo banking can be used to preserve the breed.

PMID- 11467520
TI  - The effect of estradiol benzoate or a synthetic gonadotropin-releasing hormone
      used at the start of a progesterone treatment on estrous response in cattle.
AB  - The aim was to compare the estrous response in heifers given either gonadotropin
      releasing hormone (GnRH) or estradiol benzoate (EDB) at the start of a
      progesterone treatment initiated at emergence or dominance of the first or second
      follicular wave of the estrous cycle. Cross-bred beef heifers (n=134) were
      assigned to 1 of 3 treatments; 0.75 mg EDB given at insertion of a progesterone
      releasing intravaginal device (PRID) treatment of 10 days duration (10dE2), 0.75
      mg EDB at insertion of a PRID treatment of 8 days duration with 15 mg luprostiol
      (PGF) a luteolytic agent, given 1 day before PRID removal (8dE2) or 250 microg
      GnRH at insertion of a PRID treatment of 8 days duration with 15 mg PGF given 1
      day before PRID removal (8dGnRH). Treatments were initiated on Days 2, 5, 10 or
      13 of the estrous cycle. Estrous detection was conducted six times daily. Twice
      daily blood samples were taken, from 2 days before PRID insertion until detection
      of estrus. The proportion of heifers detected in estrus was higher (P < 0.05) for
      heifers in the 8dE2 treatment group (40/40) compared with those in the 8dGnRH
      group (38/42) and tended to be higher (P = 0.08) than heifers in the 10dE2 group
      (38/41). The onset of estrus was earlier (P < 0.05) for heifers in the 10dE2
      treatment group (median 41 h, range 92 h) compared with either the 8dE2 (median
      49 h, range 64 h) or 8dGnRH groups (median 49 h, range 92 h). Submission rate at
      72 h was higher (P < 0.01) in the 8dE2 (95%) group than for those in the 10dE2
      (74%) and 8dGnRH (69%) groups. In conclusion, EDB given at PRID insertion, with
      PGF given 1 day before PRID removal, was more effective at synchronizing estrus
      than was GnRH at PRID insertion. Decreasing the length of treatment and the use
      of PGF 1 day before the end of an EDB and progesterone treatment improved estrous
      synchrony.

PMID- 11467521
TI  - Reproductive performance of postpartum dairy cows under a highly intervenient
      breeding program involving timed insemination and combinations of GnRH,
      prostaglandin F2alpha and human chorionic gonadotropin.
AB  - Lactating Holstein cows (n=288) were grouped as pairs at parturition and randomly
      assigned to two treatments (control, C vs intervenient treatment, T). The
      reproductive management of the Group C cows (n=130) consisted of the
      intramuscular administration of 500 microg PGF2alpha analogue (PG) on Days 28 and
      63 postpartum and breeding on the basis of estrus signs with the a.m.-p.m. rule
      after Day 63. Cows that were not bred by 77 d postpartum received another
      injection of PG and were bred at estrus or 84 h after PG treatment. Pregnancy
      diagnoses were perfomed by palpation of the uterus per rectum 42 to 48 d after
      AI. Cows in the T group (n=139) received intramuscular injections of 100 microg
      GnRH 14 d and PG 28 d after calving. On Day 56 postpartum, cows were given a
      second dose of GnRH followed by PG on Day 63 postpartum and a third GnRH
      injection 48 h after PG (OvSynch). Cows were inseminated at a fixed time (22+/-1
      h) after GnRH. Five days after the fixed-time insemination cows were given 1500
      IU hCG i.m.. Group C and T cows that returned to service or were diagnosed as non
      pregnant continued to receive PG at intervals of 14 d with breeding at estrus or
      84 h after the second PGF2alpha dose. A sustained increase in milk progesterone
      concentration was observed in 59.0% of T cows after GnRH administration on Day
      14. A similar rise in milk progesterone concentrations was observed in 53.8% of C
      cows. The PG on Day 28 induced luteolysis more in Group T cows (53.2%) than in
      Group C cows (36.9%). The PG on Day 63 reduced milk progesterone concentrations
      to basal levels in 50.7% of T and 49.2% of Group C animals. The first service
      pregnancy rates (T, 40.3% vs C, 36.2%) and the overall pregnancy rates (all
      services, T, 83.5% vs C, 86.9%) were not different between the two groups. The
      two treatments did not differ in the interval from first service to pregnancy,
      calving to pregnancy or in calving interval, number of services per pregnancy or
      culling rates.

PMID- 11467522
TI  - Quantification of the heterocyclic aromatic amine DNA adduct N-(deoxyguanosin-8
      yl)-2-amino-3-methylimidazo[4,5-f]quinoline in livers of rats using capillary
      liquid chromatography/microelectrospray mass spectrometry: a dose-response study.
AB  - Capillary liquid chromatography/microelectrospray-mass spectrometry (capillary
      LC/muESI-MS) was used to quantify DNA adducts of the heterocyclic aromatic amine
      2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of male Fischer-344 rats.
      Animals received a single oral dose of either 0.05, 0.50, 1.0, or 10 mg/kg IQ and
      were sacrificed 24 h following treatment. The major lesion identified at all
      doses was N-(deoxyguanosine-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8
      IQ). The capillary LC/muESI-MS method provided the means for quantifying 17.5
      fmol of dG-C8-IQ (2.0 adducts in 10(8) nucleosides) (S/N 10) in 300 microg of
      liver DNA with an intra- and interday precision of 3.5 and 6.6% (RSD),
      respectively. dG-C8-IQ was quantified with a mean intra- and interday accuracy of
      105 +/- 26 and 106 +/- 28 (SD) based on back-calculated adduct masses from five
      standard curves analyzed over a four-week period. This is the first report on
      development of a capillary LC/muESI-MS method to quantify dG-C8-IQ adducts in
      liver DNA of rats following dosing with IQ at different levels. Furthermore, the
      ability to accurately and precisely quantify dG-C8-IQ at a level of 2.0 adducts
      in 10(8) nucleosides in vivo makes this method well suited for use in future
      studies relating carcinogen exposure to risk in humans.

PMID- 11467523
TI  - Adaptation of a surface plasmon resonance biosensor with microfluidics for use
      with small sample volumes and long contact times.
AB  - The efficient delivery of sample to surface-immobilized sites is a key element in
      biosensing. For a surface plasmon resonance (SPR) biosensor, this has been
      addressed by constant flow through a microfluidic system with a sample injection
      loop (Sjolander, S.; Urbaniczky, C. Anal. Chem. 1991, 63, 2338-2345). The present
      study describes an alternative mode of sample delivery without constant
      unidirectional flow. It was implemented on a commercial Biacore X SPR biosensor
      equipped with a microfluidic cartridge, but with the fluidic handling performed
      by an externally computer-controlled syringe pump. We demonstrate that sample
      volumes as low as 2 microL can be reproducibly positioned to cover the sensor
      surfaces, manipulated in a serial fashion, efficiently mixed by applying an
      oscillatory flow pattern, and fully recovered. Compared to the traditional
      continuous unidirectional flow configuration, we found very similar kinetic
      responses at high analyte concentrations and slightly slower responses at low
      concentrations, most likely due to depletion of analyte from the small sample
      volumes due to surface binding. With the antibody-antigen systems tested, binding
      parameters were obtained that are generally within 10% of those from conventional
      experiments. In the new configuration, biosensor experiments can be conducted
      without the usual constraints in the surface contact time that are correlated
      with sample volume and mass transport rate. This can translate to improved
      detection limits for slow reactions and can facilitate kinetic and thermodynamic
      binding studies.

PMID- 11467524
TI  - Proteolytic 18O labeling for comparative proteomics: model studies with two
      serotypes of adenovirus.
AB  - A new method for proteolytic stable isotope labeling is introduced to provide
      quantitative and concurrent comparisons between individual proteins from two
      entire proteome pools or their subfractions. Two 18O atoms are incorporated
      universally into the carboxyl termini of all tryptic peptides during the
      proteolytic cleavage of all proteins in the first pool. Proteins in the second
      pool are cleaved analogously with the carboxyl termini of the resulting peptides
      containing two 16O atoms (i.e., no labeling). The two peptide mixtures are pooled
      for fractionation and separation, and the masses and isotope ratios of each
      peptide pair (differing by 4 Da) are measured by high-resolution mass
      spectrometry. Short sequences and/or accurate mass measurements combined with
      proteomics software tools allow the peptides to be related to the precursor
      proteins from which they are derived. Relative signal intensities of paired
      peptides quantify the expression levels of their precursor proteins from proteome
      pools to be compared, using an equation described in the paper. Observation of
      individual (unpaired) peptides is mainly interpreted as differential modification
      or sequence variation for the protein from the respective proteome pool. The
      method is evaluated here in a comparison of virion proteins for two serotypes
      (Ad5 and Ad2) of adenovirus, taking advantage of information already available
      about protein sequences and concentrations. In general, proteolytic 18O labeling
      enables a shotgun approach for proteomic studies with quantitation capability and
      is proposed as a useful tool for comparative proteomic studies of very complex
      protein mixtures.

PMID- 11467525
TI  - Controlled nucleation and growth of surface-confined gold nanoparticles on a (3
      aminopropyl)trimethoxysilane-modified glass slide: a strategy for SPR substrates.
AB  - The thickness of the gold film and its morphology, including the surface
      roughness, are very important for getting a good, reproducible response in the
      SPR technique. Here, we report a novel alternative approach for preparing SPR
      active substrates that is completely solution-based. Our strategy is based on
      self-assembly of the gold colloid monolayer on a (3-aminopropyl)trimethoxysilane
      modified glass slide, followed by electroless gold plating. Using this method,
      the thickness of films can be easily controlled at the nanometer scale by setting
      the plating time in the same conditions. Surface roughness and morphology of gold
      films can be modified by both tuning the size of gold nanoparticles and agitation
      during the plating. Surface evolution of the Au film was followed in real time by
      UV-vis spectroscopy and in situ SPRS. To assess the surface roughness and
      electrochemical stability of the Au films, atomic force microscopy and cyclic
      voltammetry were used. In addition, the stability of the gold adhesion is
      demonstrated by three methods. The as-prepared Au films on substrates are
      reproducible and stable, which allows them to be used as electrodes for
      electrochemical experiments and as platforms for studying SAMs.

PMID- 11467526
TI  - Electron-transfer reactivity and enzymatic activity of hemoglobin in a SP
      Sephadex membrane.
AB  - Hemoglobin can exhibit a direct electron-transfer reaction after being entrapped
      in a SP Sephadex membrane. A pair of stable and well-defined redox waves are
      obtained at a hemoglobin-SP sephadex modified pyrolytic graphite electrode. The
      anodic and cathodic peak potentials are located at -0.244 and -0.336 V (vs SCE),
      respectively. On the other hand, the peroxidase activity of the protein in the
      membrane is also greatly enhanced. The apparent Michaelis-Menten constant is
      calculated to be 1.9 mM, which shows a large catalytic activity of hemoglobin in
      the SP Sephadex membrane toward hydrogen peroxide (H2O2). According to the direct
      electron-transfer property and enhanced peroxidase activity of Hb in the
      membrane, a Hb/SP Sephadex membrane-based H2O2 biosensor is prepared, with a
      linear range approximately 5.0 x 10(-6) to 1.6 x 10(-4) mol/L.

PMID- 11467527
TI  - Electrochemical characterization of a templated insulating polymer-modified
      electrode.
AB  - The controllable permselective behavior oftemplated poly(1,2-diaminobenzene)
      modified electrodes is illustrated. The electrochemical behavior of polymer films
      prepared from several media, conventional aqueous solution, liquid crystalline
      micellar solution, and liquid crystalline hexagonal phase solution, were compared
      using several cationic and anionic redox probes. Films deposited from the
      hexagonal liquid crystalline phase were shown to be ion selective, allowing
      positively charged ions through to react at the electrode surface while excluding
      negatively charged ions. This permselective behavior was unique to the
      hexagonally templated films and was not exhibited by films deposited from either
      the conventional aqueous or the micellar media (which were completely blocking to
      both types of ion). In addition, it was shown that by altering the ionic strength
      of the background electrolyte control over the charge selective behavior of the
      hexagonally templated films was possible.

PMID- 11467528
TI  - Bioinorganic composites for enzyme electrodes.
AB  - Sparingly soluble redox salts were combined with a model enzyme, glucose oxidase,
      in a host matrix of a biopolymer chitosan to form bioinorganic composite films on
      the surface of glassy carbon electrodes. Four redox salts, each containing the
      Ru(NH3)6(3+) cation and a selected anion, such as Ru(CN)6(4-), Fe(CN)6(4-),
      Co(CN)6(3-) or IrCl6(3-), were studied. The composition and catalytic properties
      of such composite materials toward glucose oxidation were investigated by
      spectroscopic and electrochemical methods. The composite films provided an oxygen
      independent electrical communication between the enzyme's redox centers and a
      glassy carbon surface at a potential as low as -0.10 V vs Ag/AgCl(3 M Cl-). The
      nature of the electrical communication is discussed in terms of redox mediation
      by the Ru(NH3)6(3+)-containing ion pairs formed inside the biocomposites. The
      kinetic significance of the mediator's charge is considered by postulating that
      neutral ion pairs are more efficient redox mediators of the enzymatic reaction
      than those negatively charged. The low operating potential of enzyme electrodes
      based on the bioinorganic composites allows for an interference-free
      determination of glucose. The design of the biocomposites is generic and can
      incorporate oxidoreductase enzymes other than glucose oxidase to provide a host
      of biosensors for biologically and environmentally important analytes.

PMID- 11467529
TI  - A Schiff base complex of Zn(II) as a neutral carrier for highly selective PVC
      membrane sensors for the sulfate ion.
AB  - Novel polymeric membrane (PME) and coated graphite (CGE) sulfate-selective
      electrodes based on a recently synthesized Schiff base complex of Zn(II) were
      prepared. The electrodes reveal a Nernstian behavior over wide SO4(2-) ion
      concentration ranges (5.0 x 10(-5)-1.0 x 10(-1) M for PME and 1.0 x 10(-7)-1.0 x
      10(-1) M for CGE) and very low detection limits (2.8 x 10(-5) M for PME and 8.5 x
      10(-8) M for CGE). The potentiometric response is independent of the pH of the
      solution in the pH range 3.0-7.0. The electrodes manifest advantages of low
      resistance, very fast response, and, most importantly, good selectivities
      relative to a wide variety of other anions. In fact, the selectivity behavior of
      the proposed SO4(2) ion-selective electrodes shows a great improvement compared
      to the previously reported electrodes for sulfate ion. The electrodes can be used
      for at least 3 months without any appreciable divergence in potentials. The
      electrodes were used as an indicator electrode in the potentiometric titration of
      sulfate and barium ions and in the determination of iron in ferrous sulfate
      tablets.

PMID- 11467530
TI  - An acetylcholinesterase/choline oxidase-based amperometric biosensors as a liquid
      chromatography detector for acetylcholine and choline determination in brain
      tissue homogenates.
AB  - A liquid chromatography (LC) detector based on a fast response and sensitive
      bienzyme amperometric biosensor for acetylcholine (ACh) and choline (Ch) is
      described. The detector fabrication consisted of glutaraldehyde co-crosslinking
      of acetylcholinesterase and choline oxidase with bovine serum albumin on the Pt
      working electrode of a conventional thin-layer electrochemical flow cell. The
      influence of some experimental parameters (e.g., enzyme loading, thickness of the
      bienzyme layer, flow rate) on the detector characteristics has been studied in
      order to optimize the analyte response while minimizing band-broadening and
      distortion. A mobile phase consisting of a phosphate buffer (I, 0.1 M; pH, 6.5)
      containing 5 mM sodium hexane sulfonate and 10 mM tetramethylammonium phosphate
      was found to give very satisfactory resolution and peak shape in ion-pair,
      reversed-phase LC. Linear responses were observed over at least four decades and
      absolute detection limits (at a signal-to-noise ratio of 3) were 12 and 27 fmol
      injected for Ch and ACh, respectively. After one month of intensive use in the LC
      system, the detector retained about 70% of its initial sensitivity. The potential
      of the described approach is demonstrated by the simultaneous determination of Ch
      and ACh in rat brain tissue homogenates.

PMID- 11467531
TI  - Bidimensional spectroelectrochemistry.
AB  - A new methodology is presented to offer the possibility of simultaneously
      obtaining two different spectroscopic signals in a single spectroelectrochemical
      experiment. Taking the plane of the electrode surface as a spatial reference,
      normal-beam and parallel-beam UV-vis absorbance signals are jointly analyzed,
      revealing important experimental differences between the two kinds of signals.
      Two different chemical systems are selected to show the possibilities of the
      bidimensional spectroelectrochemistry: a simple diffusive process and an
      adsorptive electrode reaction. Comparative results show clearly that the two
      kinds of spectroscopic signals, both normal and parallel to the electrode
      surface, have to be used together in the study of any electrode reaction scheme.

PMID- 11467532
TI  - Elaboration and characterization of spatially controlled assemblies of
      complementary polyphenol oxidase-alkaline phosphatase activities on electrodes.
AB  - The electrooxidation of a biotin pyrrole has allowed the formation of
      biotinylated polypyrrole films. Gravimetric measurements based on a quartz
      crystal microbalance demonstrate the efficient coupling of avidin, biotinylated
      polyphenol oxidase (PPO-B) and avidin-labeled alkaline phosphatase (AP-A) with
      the underlying biotinylated polymer film. The estimated mass increase corresponds
      to the anchoring of 1.6-1.8 equivalent layer of proteins. A step-by-step
      construction of bienzyme multilayers composed of PPO-B and AP-A was carried out
      on the electrode surface modified by the biotinylated polypyrrole film through
      avidin-biotin bridges. A spatially controlled distribution of the two enzymes was
      performed by the formation of one AP-A layer on 1, 5, and 10 PPO-B layers. The
      resulting bienzyme electrodes were applied to the determination of phenyl
      phosphate on the basis of amperometric detection of enzymically generated o
      quinone at -0.2 V. Their analytical performances were analyzed in relation to the
      design of the enzyme architectures and in comparison with the amperometric
      behavior of the monoenzymatic electrodes (PPO-B electrode and AP-A electrode). It
      appears that at the 10-layer-PPO-B polypyrrole electrode only 4% of phenol is
      transformed, whereas 42-69% of phenyl phosphate is enzymatically consumed and
      detected at the AP-A polypyrrole electrode, depending on the enzyme activity. For
      the bienzymatic AP-A/PPO-B polypyrrole electrodes, the activity of each
      immobilized enzyme clearly affects the biosensor performance, the main limiting
      factor being the very low efficiency of PPO-B at pH 8.8.

PMID- 11467533
TI  - Speciation and identification of organoselenium metabolites in human urine using
      inductively coupled plasma mass spectrometry and tandem mass spectrometry.
AB  - A method for speciation and identification of organoselenium metabolites found in
      human urine samples using high performance liquid chromatography/inductively
      coupled plasma mass spectrometry (HPLC/ICP-MS) and tandem mass spectrometry
      (MS/MS) is described. Reversed-phase chromatographic separation was used for
      sample fractionation with the ICP-MS functioning as an element-selective
      detector, and six distinct selenium-containing species were detected in a human
      urine sample. Fractions were then collected and analyzed using a triple
      quadrupole mass spectrometer with electrospray ionization and collision-induced
      dissociation to obtain structural information. The first two fractions were
      identified specifically as selenomethionine and selenocystamine, estimated to be
      present at approximately 11 and 40 ppb, respectively. To the best of our
      knowledge, this is the first time these two metabolites have been positively
      identified in human urine.

PMID- 11467534
TI  - An atmospheric pressure glow discharge optical emission source for the direct
      sampling of liquid media.
AB  - A glow discharge optical emission spectroscopy (GD-OES) source that operates at
      atmospheric pressure is described. This device utilizes an electrolytic solution
      containing the analyte specimen as one of the discharge electrodes. The passage
      of electrical current (either electrons or positive ions) across the solution/gas
      phase interface causes local heating and the volatilization of the analyte
      species. Collisions in the discharge region immediately above the solution
      surface result in optical emission that is characteristic of the analyte
      elements. Operation of this device with the analyte solution acting as either the
      cathode or anode is demonstrated. Current-voltage (i-V) plots reveal abnormal
      glow discharge characteristics, with operating parameters being dependent on the
      electrolyte concentration (i.e., solution conductivity) and the gap between the
      solution surface and the counterelectrode. Typical conditions include discharge
      currents of 30-60 mA, and potentials of 500-900 V. Electrolyte solutions having
      pH, pNa, or pLi values of 0.5-2 and interelectrode gaps of 0.5-3 mm produce
      stable plasmas in which the analyte solutions flow at rates of up to 3.0 mL/min.
      Preliminary limits of detection are determined for the elements Na, Fe, and Pb to
      be in the range of 11-14 ppm (approximately 60 ng) for 5-microL sample volumes.

PMID- 11467535
TI  - Sources of uncertainty in isotope ratio measurements by inductively coupled
      plasma mass spectrometry.
AB  - A model is presented describing the effects of dead time and mass bias correction
      factor uncertainties, flicker noise, and counting statistics on isotope ratio
      measurement precision using inductively coupled plasma mass spectrometry (ICPMS)
      with a single collector. Noise spectral analysis is exploited to enable
      estimation of the flicker noise parameters. For the instrument used, the flicker
      noise component exhibited a fairly weak frequency (t) dependence (is proportional
      to f -0.33+/-0.12), but was directly proportional to the total number of counts,
      Q. As white noise, determined by counting statistics, is given by Q0.5, the
      isotope ratio measurement uncertainties will actually cease to improve when Q
      exceeds a certain threshold. This would suggest that flicker noise could become
      the limiting factor for the precision with which isotope ratios can be determined
      by ICPMS. However, under most experimental conditions, uncertainties associated
      with mass discrimination and dead time correction factors are decisive. For
      ratios up to approximately 22 (115In/113In), optimum major isotope count rates
      are generally below 0.3 MHz, for which precision in the mass discrimination
      factor is limiting. The model derived could be used as a starting point for
      determining optimum conditions and understanding the limitations of single
      collector ICPMS for precise isotope ratio measurements.

PMID- 11467536
TI  - Imaging of conformational changes of proteins with a new environment-sensitive
      fluorescent probe designed for site-specific labeling of recombinant proteins in
      live cells.
AB  - We demonstrate herein a new method for imaging conformational changes of proteins
      in live cells using a new synthetic environment-sensitive fluorescent probe, 9
      amino-6,8-bis(1,3,2-dithioarsolan-2-yl)-5H-benzo[a]phenoxazin-5-one. This
      fluorescent probe can be attached to recombinant proteins containing four
      cysteine residues at the i, i + 1, i + 4, and i + 5 positions of an alpha-helix.
      The specific binding of the fluorescent probe to this 4Cys motif enables
      fluorescent labeling inside cells by its extracellular administration. The high
      sensitivity of the fluorophore to its environment enables monitoring of the
      conformational changes of the proteins in live cells as changes in its
      fluorescence intensity. The present method was applied to calmodulin (CaM), a
      Ca2+-binding protein that was well-known to expose hydrophobic domains, depending
      on the Ca2+ concentration. A recombinant CaM fused at its C-terminal with a
      helical peptide containing a 4Cys motif was labeled with the fluorescent probe
      inside live cells. The fluorescence intensity changed reversibly depending on the
      intracellular Ca2+ concentration, which reflected the conformational change of
      the recombinant CaM in the live cells.

PMID- 11467537
TI  - Nanoliter solvent extraction combined with microspot MALDI TOF mass spectrometry
      for the analysis of hydrophobic biomolecules.
AB  - A nanoliter solvent extraction technique combined with microspot matrix-assisted
      laser desorption/ionization (MALDI) mass spectrometry is presented. This method
      involves the use of a nanoliter droplet containing organic solvents at the tip of
      a small capillary for extraction. The droplet is formed inside a microliter
      aqueous sample containing the analyte of interest. After extraction, the droplet
      is deposited onto a MALDI target precoated with a thin matrix layer. Since the
      nanoliter droplet never touches the sample container wall, any possible
      extraction of contaminants adsorbed on the plastic or glassware is avoided. In
      addition, there is no need to concentrate the organic phase after the extraction,
      thus avoiding any possible loss during the concentration step. The nanoliter
      volume can be readily deposited onto a MALDI target, producing a high analyte
      concentration within a microspot. Combined with microspot MALDI, this technique
      allows for very sensitive analysis of the extracted analyte. The performance of
      this technique is illustrated in several applications involving the detection of
      hydrophobic peptides or phospholipids. It is shown that very hydrophobic analytes
      can be extracted from small-volume samples containing a large amount of salts
      and/or more hydrophilic analytes, which tend to give dominant signals in
      conventional MALDI experiments. Nanoliter extraction of analyte from samples
      containing less than 100 nM hydrophobic analyte and over 1 microM easily ionized
      hydrophilic species is demonstrated. Finally, using the analysis of the ionophore
      valinomycin as an example, it is demonstrated that the technique is a more
      reliable tool for probing metal-peptide complexes than regular MALDI sample
      preparations.

PMID- 11467538
TI  - Mass spectrometry for on-line monitoring of perfluoro compounds using Li+ ion
      attachment techniques.
AB  - Ion attachment mass spectrometry is being developed for continuous measurement of
      perfluoro compounds (PFCs) found in the atmosphere as a result of semiconductor
      manufacturing processes. Studies were made on 5 greenhouse gases, CF4, CHF3,
      C2F6, SF6, and c-C4F8, to develop improved methods for PFC analysis, particularly
      at levels found in the atmosphere (the parts-per-billion concentration range).
      The results demonstrate the feasibility of performing real-time measurements of
      the trace amounts of PFCs encountered in process facilities by generating adduct
      ions from Li+ ion attachment. The identification and detection of c-C4F8 is
      described as an example of the utility of this new method.

PMID- 11467539
TI  - Mass spectrometry screening of combinatorial mixtures, correlation of measured
      and predicted electrospray ionization spectra.
AB  - Methodology was developed to afford rapid characterization of multicomponent
      mixtures of small organic molecules prepared by split-and-mix combinatorial
      synthesis. This methodology involved the use of liquid chromatography mass
      spectrometry (LC/MS) combined with correlation analysis of measured versus
      predicted electrospray ionization mass spectra. Low-resolution mass spectra of
      complex mixtures revealed predictable patterns that confirm library products,
      assisted in identifying chemical synthesis errors, and assessed overall library
      integrity. In general, equal signal intensities were observed for most
      combinatorial mixture components, indicating that differences in electrospray
      ionization efficiency was not a major limitation to this approach. High
      throughput data processing programs and informatics tools were used to speed data
      analysis and to simplify the presentation of the library characterization
      results. This approach has been used to characterize combinatorial libraries that
      were synthesized for a variety of drug-discovery programs. Examples are shown for
      library formats of 1, 40, 66, 280, and 400 component(s)/well. The applicability
      of this approach to large combinatorial mixtures should allow direct
      characterization of massive combinatorial libraries.

PMID- 11467540
TI  - Detection of viable Cryptosporidium parvum using DNA-modified liposomes in a
      microfluidic chip.
AB  - This paper describes a microfluidic chip that enables the detection of viable
      Cryptosporidium parvum by detecting RNA amplified by nucleic-acid-sequence-based
      amplification (NASBA). The mRNA serving as the template for NASBA is produced by
      viable C. parvum as a response to heat shock. The chip utilizes sandwich
      hybridization by hybridizing the NASBA-generated amplicon between capture probes
      and reporter probes in a microfluidic channel. The reporter probes are tagged
      with carboxyfluorescein-filled liposomes. These liposomes, which generate
      fluorescence intensities not obtainable from single fluorophores, allow the
      detection of very low concentrations of targets. The limit of detection of the
      chip is 5 fmol of amplicon in 12.5 microL of sample solution. Samples of C.
      parvum that underwent heat shock, extraction, and amplification by NASBA were
      successfully detected and clearly distinguishable from controls. This was
      accomplished without having to separate the amplified RNA from the NASBA mixture.
      The microfluidic chip can easily be modified to detect other pathogens. We
      envision its use in mu-total analysis systems (mu-TAS) and in DNA-array chips
      utilized for environmental monitoring of pathogens.

PMID- 11467541
TI  - Standardless semiquantitative analysis of metals using single-shot laser ablation
      inductively coupled plasma time-of-flight mass spectrometry.
AB  - A method has been developed that allows the accurate, standardless measurement of
      the elemental composition of metal samples from single laser ablation (LA)
      pulses. This technique provides a fast, low-sample-consumption means for the
      characterization of samples having a range of matrixes. The method directly
      compares adjusted elemental signals with the total mass spectrometric signal to
      produce relative percent composition information. Three mathematical techniques
      were used to determine the accuracy and precision of single-shot LA measurement.
      Comparison of the techniques showed that a linear regression calculation, which
      plots individual elemental signals as a function of the summed signal for all
      elements in the sample on a point-by-point basis during a laser ablation
      transient proved superior. The simultaneous extraction capability of time-of
      flight mass spectrometry permits the sampling of all analytes from any temporal
      position within the transient laser ablation pulse, thereby reducing quantitation
      error. A typical concentration dynamic range of 3 orders of magnitude, from 0.1
      to 100%, was achieved. However, by measuring low-abundance isotopes for matrix
      elements, the dynamic range of the technique was extended to 4 orders of
      magnitude. The new technique is largely immune to sample matrix effects commonly
      experienced in laser ablation. By performing a complete elemental analysis from a
      single ablation pulse, high spatial resolution should be achieved.

PMID- 11467542
TI  - Two-layer sample preparation method for MALDI mass spectrometric analysis of
      protein and peptide samples containing sodium dodecyl sulfate.
AB  - Sodium dodecyl sulfate (SDS) is widely used in protein sample workup. However,
      many mass spectrometric methods cannot tolerate the presence of this strong
      surfactant in a protein sample. We present a practical and robust technique based
      on a two-layer matrix/sample deposition method for the analysis of protein and
      peptide samples containing SDS by matrix-assisted laser desorption ionization
      mass spectrometry (MALDI-MS). The two-layer method involves the deposition of a
      mixture of sample and matrix on top of a thin layer of matrix crystals. It was
      found that for SDS-containing samples, the intensity of the MALDI signals can be
      affected by the conditions of sample preparation: on-probe washing, choice of
      matrix, deposition method, solvent system, and protein-to-SDS ratio. However, we
      found that, under appropriate conditions, the two-layer method gave reliable
      MALDI signals for samples with levels of SDS up to approximately 1%. The
      applications of this method are demonstrated for MALDI analysis of hydrophobic
      membrane proteins as well as bacterial extracts. We envision that this two-layer
      method capable of handling impure samples including those containing SDS will
      play an important role in protein molecular weight analysis as well as in
      proteome identification by MALDI-MS and MS/MS.

PMID- 11467543
TI  - Evaluation and optimization of ion-current ratio measurements by selected-ion
      monitoring mass spectrometry.
AB  - Stable isotopically labeled compounds are regularly used as internal standards in
      quantitation and as tracers of in vivo metabolism. In both applications, the
      ratio of unlabeled to labeled analogues is determined from an ion-current ratio
      measured by a mass spectrometer. The precision of the ion-current ratio
      measurement defines the detection limit for quantitation and for tracer
      enrichment measurement. We have used standard models of noise to develop a method
      that evaluates ion-current ratio noise (i) that varies with the signal intensity
      and (ii) that is signal independent. This model produces a simple equation that
      defines the ion-current ratio precision using constants that can be evaluated
      empirically from the measurement of two ion-current ratios from a single standard
      measured multiple times. We demonstrate that our approach can predict the effect
      of signal intensity, ion-current ratio magnitude, and internal standard or tracer
      choice on the measurement precision. The standard deviations predicted by our
      method are shown to equal standard deviations of samples measured experimentally.
      This method allows a simple evaluation of a mass spectrometry system and can
      define the precision of new quantitation and tracer methods.

PMID- 11467544
TI  - Very high pressure gradient LC/MS/MS.
AB  - A very high pressure liquid chromatography (VHPLC) system was constructed by
      modifying a commercially available pump in order to achieve pressures in excess
      of 1,200 bar (17,500 psi). A computer-controlled low-pressure mixer was used to
      generate solvent gradients. Protein digests were rapidly analyzed by reversed
      phase VHPLC with linear solvent gradients coupled to either a tandem mass
      spectrometer using electrospray ionization or a UV/visible detector. The
      separations were performed at pressures ranging from 790 (11,500 psi) to 930 bar
      (13,500 psi) in 22-cm-long capillary columns packed with C18-modified 1.5-microm
      nonporous silica particles. A digest of bovine serum albumin (BSA) was analyzed
      by the VHPLC system connected to a mass spectrometer in MS mode. An analysis of
      12.5 fmol of sample gave signal-to-noise ratios of tryptic peaks greater than
      10:1 in the base peak plot mass chromatogram. This system was also used to
      analyze a proteolytic digest of a rat liver protein excised from a 2-D gel
      separation of a liver tissue lysate. For this analysis, the mass spectrometer was
      set up to perform data-dependent scanning (automated switching from MS mode to
      MS/MS mode when a peak was detected) for peptide sequencing and protein
      identification by database searching. The results of this analysis are compared
      to an analysis performed on the same sample using the nanoelectrospray-MS/MS
      technique. Though both techniques were able to identify the unknown protein, the
      VHPLC method gave twice as many sequenced peptides as nanoelectrospray and
      improved the signal-to-noise ratio of the spectra by at least a factor of 10.
      Direct comparisons with nanoelectrospray for MS and MS/MS data acquisition from a
      BSA digest were made. These comparisons show enhancements of greater than 20-fold
      for VHPLC over nanoelectrospray. In addition, the VHPLC/MS/MS data acquisition
      was accomplished in an automated manner.

PMID- 11467545
TI  - Formaldehyde in human cancer cells: detection by preconcentration-chemical
      ionization mass spectrometry.
AB  - A rapid and highly sensitive method for the detection of formaldehyde utilizing
      selected ion flow tube-chemical ionization mass spectrometry is reported.
      Formaldehyde in aqueous biological samples is preconcentrated by distillation and
      directly analyzed using gas-phase thermal energy proton transfer from H30+; this
      procedure can be performed in 30 min. The method detection limit for formaldehyde
      based on seven replicate measurements of reference water samples (2.5 mL) is 80
      nM at the 99% confidence level. Detection is linear up to 130 microM. This
      technique allows the first measurement of natural formaldehyde levels in human
      cancer cells in vitro. Elevated levels of formaldehyde relative to the reference
      water are observed for doxorubicin-sensitive cells (MCF-7 breast cancer, K562
      leukemia, HeLa S3 cervical cancer) with estimated intracellular formaldehyde
      concentrations ranging from 1.5 to 4.0 microM, whereas formaldehyde in
      doxorubicin-resistant MCF-7/Adr breast cancer cells is essentially at reference
      level. This trend is inverted for prostate cancer cells LNCaP (sensitive) and DU
      145 (resistant). Correlation of natural formaldehyde level with doxorubicin
      cytotoxicity is a function of the expression of enzymes that neutralize oxidative
      stress and the drug efflux pump, P-170 glycoprotein.

PMID- 11467546
TI  - Advantages of external accumulation for electron capture dissociation in Fourier
      transform mass spectrometry.
AB  - A combination of external accumulation (XA) with electron capture dissociation
      (ECD) improves the electron capture efficiency, shortens the analysis time, and
      allows for rapid integration of multiple scans in Fourier transform mass
      spectrometry. This improves the signal-to-noise ratio and increases the number of
      detected products, including structurally important MS3 fragments. With XA-ECD,
      the range of the labile species amenable to ECD is significantly extended.
      Examples include the first-time determination of the positions of six GalNAc
      groups in a 60-residue peptide, five sialic acid and six O-linked GalNAc groups
      in a 25-residue peptide, and the sulfate group position in a 11-residue peptide.
      Even weakly bound supramolecular aggregates, including nonspecific peptide
      complexes, can be analyzed with XA-ECD. Preliminary results are reported on high
      rate XA-ECD that uses an indirectly heated dispenser cathode as an electron
      source. This shortens the irradiation time to > or = 1 ms and increases the
      acquisition rate to 3 scans/s, an improvement by a factor of 10-100.

PMID- 11467547
TI  - Protein phosphorylation degree: determination by capillary liquid chromatography
      and inductively coupled plasma mass spectrometry.
AB  - Capillary liquid chromatography (muLC) interfaced to inductively coupled plasma
      mass spectrometry (ICPMS) is introduced as a new micromethod to determine the
      phosphorylation degree in phosphoproteins and phosphopeptides containing cysteine
      and/or methionine residues. The stoichiometric phosphorus to sulfur (31P to 32S)
      ratio is experimentally determined by muLC-ICPMS and converted into the degree of
      phosphorylation using protein/ peptide sequence information. The method is
      applied to the phosphoproteins beta-casein, beta-casein, and recombinant protein
      kinase A catalytic subunit and to synthetic phosphopeptides. The accurate data
      obtained by muLC-ICPMS allow quantitative assessment of the compound-specific
      discrimination of the electrospray ionization process between nonphosphorylated
      and phosphorylated proteins and peptides.

PMID- 11467548
TI  - High-throughput proteomics using high-efficiency multiple-capillary liquid
      chromatography with on-line high-performance ESI FTICR mass spectrometry.
AB  - We report on the design and application of a high-efficiency multiple-capillary
      liquid chromatography (LC) system for high-throughput proteome analysis. The
      multiple-capillary LC system using commercial LC pumps was operated at a pressure
      of 10,000 psi to deliver mobile phases through a novel passive feedback valve
      arrangement that permitted mobile-phase flow path switching and efficient sample
      introduction. The multiple-capillary LC system uses several serially connected
      dual-capillary column devices. The dual-capillary column approach eliminates the
      time delays for column regeneration (or equilibration) since one capillary column
      was used for a separation while the other was being washed. Several serially
      connected dual-capillary columns and electrospray ionization (ESI) sources were
      operated independently and can be used either for "backup" operation or for
      parallel operation with other mass spectrometers. This high-efficiency multiple
      capillary LC system utilizes switching valves for all operations, enabling
      automated operation. The separation efficiency of the dual-capillary column
      arrangement, optimal capillary dimensions (column length and packed particle
      size), capillary regeneration conditions, and mobile-phase compositions and their
      compatibility with electrospray ionization were investigated. A high magnetic
      field (11.4 T) Fourier transform ion cyclotron resonance (FTICR) mass
      spectrometer was coupled on-line with this high-efficiency multiple-capillary LC
      system using an ESI interface. The capillary LC provided a peak capacity of
      approximately 650, and the 2-D capillary LC-FTICR analysis provided a combined
      resolving power of > 6 x 10(7) components. For yeast cytosolic tryptic digests >
      100,000 polypeptides were detected, and approximately 1,000 proteins could be
      characterized from a single capillary LC-FTICR analysis using the high mass
      measurement accuracy (approximately 1 ppm) of FTICR, and likely more if LC
      retention time information were also exploited for peptide identification.

PMID- 11467549
TI  - A mechanism of separation in electrostatic ion chromatography.
AB  - The retention mechanism of electrostatic ion chromatography (EIC) is currently
      under debate and is the focus of this paper. A comprehensive set of retention
      data has been obtained on a C18 column coated with the zwitterionic surfactant 3
      (N,N-dimethylmyristylammonio)propanesulfonate used with a range of mobile phases
      in which both the mobile-phase anion and cation have been varied systematically.
      Electro-osmotic flow measurements were also obtained on fused-silica capillaries
      coated with the zwitterion (and also some monofunctional surfactants) and were
      used to evaluate the nature of the surface charge on the layer of adsorbed
      surfactant in the presence of various background electrolytes. A new retention
      mechanism for EIC was developed on the basis of these data. This mechanism
      proposes that equilibration of the bound zwitterions with a mobile phase
      containing a suitable electrolyte causes the establishment of a charged layer
      created by the terminal sulfonate groups of the zwitterion, which acts as a
      Donnan membrane. The magnitude and polarity of the charge on this membrane
      depends on the nature of the mobile-phase ions. The Donnan membrane exerts weak
      electrostatic repulsion or attraction effects on analyte anions. A second
      component of the retention mechanism is chaotropic interaction of the analyte
      anion with the quaternary ammonium functional group of the zwitterion. This
      interaction exerts the major effect on the separation selectivity of EIC, such
      that analyte anions are eluted in order of increasing chaotropic interactions in
      accordance with the Hofmeister series.

PMID- 11467550
TI  - Electrospray ionization high-resolution ion mobility spectrometry for the
      detection of organic compounds, 1. Amino acids.
AB  - Our aim in this investigation was to demonstrate the potential of the high
      resolution electrospray ionization ion mobility spectrometry (ESI-IMS) technique
      as an analytical separation tool in analyzing biomolecular mixtures to pursue
      astrobiological objectives of searching for the chemical signatures of life
      during an in-situ exploration of solar system bodies. Because amino acids
      represent the basic building blocks of life, we used common amino acids to
      conduct the first part of our investigation, which is being reported here, to
      demonstrate the feasibility of using the ESI-IMS technique for detection of the
      chemical signatures of life. The ion mobilities of common amino acids were
      determined by electrospray ionization ion mobility spectrometry using three
      different drift gases (N2, Ar, and CO2). We demonstrated that the selectivity can
      be vastly improved in ion mobility spectroscopy (IMS) in detecting organic
      molecules by using different drift gases. When a judicial choice of drift gas is
      made, a vastly improved separation of two different amino acid ions resulted. It
      was found that each of the studied amino acids could be uniquely identified from
      the others, with the exception of alanine and glycine, which were never separable
      by more then 0.1 ms. This unique identification is a result of the different
      polarizabilities of the various drift gases. In addition, a better separation was
      achieved by changing the drift voltage in successive experimental runs without
      significantly degrading the resolution. We also report the result of our analysis
      of liquid samples containing mixtures of amino acids.

PMID- 11467551
TI  - Shear-induced degradation of linear polyacrylamide solutions during pre
      electrophoretic loading.
AB  - Electrophoretic channels are filled with a polymer matrix prior to their use in
      DNA separations. This process, called gel-loading, can be accomplished manually,
      using syringes, or can be automated through the use of small pumps or vacuum. The
      injection rate is constrained by the desire to minimize shear-induced degradation
      of the polymer molecules. Currently, the community lacks quantitative data with
      which to gauge the range of flow rates that prevent polymer degradation. In this
      study, measurements of the zero shear rate viscosity of linear polyacrylamide
      (LPA) solutions are used to determine the LPA molecular weight before and after
      gel-loading. The results indicate molecular degradation in polymer solutions even
      when injected at minimal flow rates of 1 microL/min. To correlate these
      rheological observations of shear-induced degradation with subsequent
      electrophoretic performance, the degraded solutions were used as sieving matrixes
      for DNA sequencing analysis. The decreases in electrophoretic resolution and
      increases in peak widths between sheared and nonsheared LPA solutions are related
      to the degradation in molecular weight experienced by the polymer solutions.

PMID- 11467552
TI  - High-speed GC and GC/MS with a series-coupled column ensemble using stop-flow
      operation.
AB  - A pneumatically actuated valve is used to connect the junction point of a series
      coupled column ensemble to a ballast chamber containing carrier gas at the
      ensemble inlet pressure in order to periodically stop the carrier gas flow in the
      first column. When the valve is opened, mixture components, which have migrated
      across the column junction, are accelerated toward a time-of-flight mass
      spectrometer that is used as an ensemble detector. Mixture components, which are
      still in the first column, are frozen in position. This allows for the insertion
      of time windows into the ensemble chromatogram that can aid in the separation of
      some overlapping component peaks. The capillary column ensemble (0.18-mm i.d. x
      0.18-microm film thickness) consists of a 7.0-m length of polar,
      (trifluoropropyl)methyl polysiloxane column followed by a 7.0-m length of
      nonpolar dimethyl polysiloxane column. A flame ionization detector located at the
      column junction point is used to monitor a portion of the effluent from the first
      column in order to determine the valve timing sequence needed to enhance the
      separation of component pairs that are separated by the first column but coelute
      from the column ensemble. When one of the components of a targeted pair has
      crossed the junction but the other component is still in the first column, the
      valve is opened, typically for 1-5 s. The stop-flow system is used to enhance the
      separation of a mixture containing some common essential oil components and a
      mixture containing some common pesticides.

PMID- 11467553
TI  - Chromatographic probing of electrostatic potential.
AB  - Electrostatic potential in the vicinity of the surface of a cation-exchange resin
      has been evaluated by modeling chromatographic retention. Binary mixtures of K+
      and its crown ether complex in methanol are used as mobile phases, and two types
      of solutes, that is, cationic and crown ether probes, have been examined. The
      cationic probes show the sigmoidal retention changes with increasing
      concentration of a crown ether incorporated into the mobile phase, whereas crown
      ether probes give retention maximums. The model derived from the Poisson
      Boltzmann theory well explains these specific changes in probe retention and
      gives the electrostatic potential at the closest approach of each probe molecule.
      The closest approaches for probe molecules correlate well with their molecular
      sizes. In addition, changes in retention of cationic probes also correlate well
      with the electrostatic potential changes at the closest approaches of probe
      molecules, indicating that simple sensing of the electrostatic potential is
      feasible using probe retention. The reduction of crown ether complexation occurs
      in the vicinity of the cation-exchange resin surface and causes the specific
      retention behaviors of crown ether probes in the mobile-phase systems composed of
      K+ and its complex with a modifier crown ether.

PMID- 11467554
TI  - A mathematical model for hydrodynamic and size exclusion chromatography of
      polymers on porous particles.
AB  - When packed columns filled with porous particles are used for the separation of
      macromolecules, either size exclusion chromatography (SEC), hydrodynamic
      chromatography (HDC), or a combination of both determine the macromolecule
      retention mechanism. This paper develops a simple mathematical model to describe
      a molecular weight calibration graph, which includes both HDC and SEC. There is a
      transition between the HDC calibration region at higher molecular weights to an
      SEC region at lower molecular weights. The degree to which SEC and HDC are mixed
      depends on the particle diameter, the relative size of the pores, and the
      macromolecule size. In addition, using fractal considerations, the fractal
      character of the apparent selectivity between two adjacent peaks on the
      chromatogram is shown. This model constitutes an attractive tool to enhance the
      expansion of these two chromatographic techniques for the separation of
      biological or synthetical macromolecules.

PMID- 11467555
TI  - Field-amplified sample injection combined with water removal by electroosmotic
      flow pump in acidic buffer for analysis of phenoxy acid herbicides by capillary
      electrophoresis.
AB  - A procedure that combines two common stacking techniques, field-amplified sample
      injection and water removal, with an electroosmotic flow pump, is used to
      separate phenoxy acid herbicides by capillary zone electrophoresis. Before sample
      loading, a long plug of water was hydrodynamically injected into the capillary
      both to serve as the medium to permit a high electric field strength and to
      contain sample anions. Because of this long length of water, the number of ions
      injected into the capillary was greatly increased. Electrokinetic injection at
      reversed voltage was then used for introducing negatively charged ions from the
      diluted sample into the column. The water was removed from the capillary using
      the electroosmotic flow (EOF) pump when the EOF of the background electrolyte was
      suppressed. This method afforded a sensitivity enhancement of greater than 3,000
      times. Combined with solid-phase extraction, detection limits for the phenoxy
      acid herbicides as low as 0.01 ng/mL could be achieved.

PMID- 11467556
TI  - Determination of alkylphenols after derivatization to ferrocenecarboxylic acid
      esters with gas chromatography-atomic emission detection.
AB  - A method is described for the rapid determination of alkylphenols in nonpolar
      matrixes. The alkylphenols are derivatized with ferrocenecarboxylic acid chloride
      so that every phenol molecule is labeled with one iron atom. The resulting esters
      are analyzed by gas chromatography with atomic emission detection (AED) in the
      iron-selective detection mode. This method utilizes the AED's low detection limit
      (0.05 pg/s) for iron and the high selectivity versus carbon (3.5 x 10(6)) for the
      detection of the alkylphenols. Because the derivatization is performed before the
      first step of sample preparation, the risk of analyte loss by adsorption or
      volatilization is minimized. The total recoveries in the lower ppm concentration
      range vary between 79 and 125%. The quantification of 20 C0-C3-alkylphenols in
      crude oils is demonstrated by analyzing a shale oil (SRM 1580) and a petroleum
      crude oil (SRM 1582). The complete workup is easily carried out in only 45
      min/sample.

PMID- 11467557
TI  - Increasing bioanalytical throughput using pcSFC-MS/MS: 10 minutes per 96-well
      plate.
AB  - The utility of packed-column supercritical, subcritical, and enhanced fluidity
      liquid chromatographies (pcSFC) for high-throughput applications has increased
      during the past few years. In contrast to traditional reversed-phase liquid
      chromatography, the addition of a volatile component to the mobile phase, such as
      CO2, produces a lower mobile-phase viscosity. This allows the use of higher flow
      rates which can translate into faster analysis times. In addition, the resulting
      mobile phase is considerably more volatile than the aqueous-based mobile phases
      that are typically used with LC-MS, allowing the entire effluent to be directed
      into the MS interface. High-throughput bioanalytical quantitation using pcSFC
      MS/MS for pharmacokinetics applications is demonstrated in this report using
      dextromethorphan as a model compound. Plasma samples were prepared by automated
      liquid/liquid extraction in the 96-well format prior to pcSFC-MS/MS analysis.
      Three days of validation data are provided along with study sample data from a
      patient dosed with commercially available Vicks 44. Using pcSFC and MS/MS,
      dextromethorphan was quantified in 96-well plates at a rate of approximately 10
      min/plate with average intraday accuracy of 9% or better. Daily relative standard
      deviations (RSDs) were less than 10% for the 2.21 and 14.8 ng/mL quality control
      (QC) samples, while the RSDs were less than 15% at the 0.554 ng/mL QC level.

PMID- 11467558
TI  - Silyl derivatization of alkylphenols, chlorophenols, and bisphenol A for
      simultaneous GC/MS determination.
AB  - A fast silyl derivatization technique for simultaneous GC/ MS analysis of
      alkylphenols, chlorophenols, and bisphenol A was developed. The analytes were
      silylized with an excess amount of bis(trimethylsilyl)trifluoroacetamide (BSTFA)
      followed by hydrolysis of excess silyl reagent with water. Reaction rates of
      derivatization were studied in various solvents and found to be fastest in
      acetone. Derivatization reaction in acetone was completed quantitatively within
      15 s at room temperature while it took more than 1 h in other solvents studied.
      Similar results were obtained in mixed solvents with acetone if the content of
      acetone was higher than 60% (v/v). Since water-immiscible solvents such as
      dichloromethane or hexane are frequently used in the extraction of phenolic
      analytes in various sample matrixes, acetone can be added to the extracts in
      order to accelerate the reaction rate of derivatization. Stability of the
      derivatives in sample for long-term storage was ensured by hydrolyzing excess
      derivatizing reagent, BSTFA, with a spike of water followed by dehydration using
      anhydrous sodium sulfate. On the basis of the above results, a derivatizing
      treatment kit was designed to improve the convenience of analysis. It was
      possible to treat sample within several minutes successfully by using the kit. So
      fast simultaneous determination of those anlaytes by GC/MS was possible with
      improved convenience as well as sensitivity and reproducibility.

PMID- 11467559
TI  - Analysis of the surface diffusion of alkylbenzenes and p-alkylphenols in reversed
      phase liquid chromatography using the surface-restricted molecular diffusion
      model.
AB  - Surface diffusion of alkylbenzene and p-alkylphenol derivatives was measured in
      reversed-phase liquid chromatography on a C18-silica column with a methanol/water
      mixture (70/30, v/v) as the mobile phase. They were analyzed on the basis of the
      restricted molecular diffusion model for surface diffusion. The temperature
      dependence of the surface diffusion coefficient (Ds) arises probably from that of
      molecular diffusivity, suggesting a correlation between surface and molecular
      diffusion. Other correlations were also observed: (1) an enthalpy-entropy
      compensation of the retention equilibrium constant, (2) a linear free energy
      relationship between the retention and surface diffusion, and (3) a linear
      correlation between the restriction energy of surface diffusion and the isosteric
      heat of adsorption. The physical meaning of parameters involved in the surface
      restricted molecular diffusion model is discussed on the basis of these results.
      A practical and convenient procedure for the estimation of Ds is also suggested.
      This study demonstrates how surface diffusion phenomena can be accounted for on
      the basis of the correlation between surface and molecular diffusion.

PMID- 11467560
TI  - Measurement of insecticide uptake and effective fraction in a beneficial insect
      using solid-phase microextraction.
AB  - The determination of insecticide uptake in beneficial insects is important for
      quantifying the doses that are responsible for the toxicological effects and to
      compare them with the doses that insects may absorb in treated fields. Because of
      the small size of some beneficial species, the amount of insecticide absorbed may
      be very low. Herein, we present a method that relies on the sensitivity and
      specificity of SPME (solid-phase microextraction) as a sampling technique that
      can be used to measure very small amounts of an organophosphorus insecticide in
      small insects. In our study, the method was applied to quantify the internal dose
      and free dissolved fraction of chlorfenvinphos in beneficial parasitoids exposed
      through a topical application. Up to 0.5 ng of the insecticide could be
      quantified in these fractions, that is, 10 times less than when using solvent
      extraction techniques. The penetration and elimination rates of the insecticide
      in the insect were also determined. The method proved to be suitable to quantify
      internal doses in parasitoids collected in a treated field.

PMID- 11467561
TI  - Band-trajectory model for temperature-programmed series-coupled column ensembles
      with pressure-tunable selectivity.
AB  - A model and a spreadsheet algorithm is described for the prediction of solute
      band migration trajectories in a series-coupled combination of two capillary GC
      columns with pressure-tunable and -programmable selectivity and operated under
      temperature-programmed conditions. The model takes into account the acceleration
      of carrier gas in the two columns as a result of decompression effects, the
      deceleration of carrier gas as a result of the increase in viscosity during
      temperature programming, the decrease in solute retention factors with increasing
      temperature during the temperature program, the differences in retention factors
      for the two columns, and programmed changes in the carrier-gas flow rates in the
      two columns during selectivity programming. In the model, the 20-meter-long
      column ensemble is divided into 1-cm-long intervals, and the carrier-gas velocity
      and column temperature are assummed to be constant in any interval. Migration
      times for all of the mixture solutes are computed for each column interval, and
      the solute-band positons in the column ensemble are plotted versus the running
      sum of these migration times to obtain band trajectory plots. The sum of these
      migration times for all 2,000 intervals gives the ensemble retention times for
      the solutes. Isothermal retention factors (k) for all of the mixture components
      at various column temperatures (Tc) are used as imput to the algorithm. Slope and
      intercept values of In(k) vs 1/Tc plots are used in the algorithm. General
      features of the model are tested using a mixture of C12-C24 normal alkanes. A
      mixture of polar and nonpolar compounds is used to test the utility of the model
      for the predicition of peak separations and retention times with pressure-tunable
      and -programmable selectivity. Good agreement is observed in all cases.

PMID- 11467562
TI  - Feasibility of high-performance immunochromatography as an isolation method for
      PCBs and other dioxin-like compounds.
AB  - A high performance immunochromatographic procedure to isolate polychlorinated
      biphenyls (PCBs) and other dioxin-like compounds from a sample is shown.
      Development of the procedure includes (i) synthesis of the hapten, binding it to
      the spacer arm and to the carrier protein to make the immunizing molecule; (ii)
      raising and purification of anti-PCB antibodies; (iii) building of the
      immunocolumn; (iv) selection of the binding, rinsing, and elution conditions
      adequate for these highly lipophilic compounds; (v) study of the influence of the
      concentration and volume of sample on recovery; and (vi) study of the selectivity
      of the immunosystem for dioxins, furans, PCBs, and several insecticides of
      different toxicity. Evaluation of the method is carried out by analyzing the
      fractions retained and nonretained in the immunocolumn by GC/MS. The
      immunochromatographic system that is developed shows itself to be feasible as
      cleanup and isolation steps carried out prior to GC/MS analyses. When compared to
      classical cleanup and isolation methods traditionally used for analysis of PCBs
      in water, the immunochromatographic method is > 20x faster and uses 100x less
      organic solvents, and its selectivity is enormously enhanced. Good recoveries are
      obtained with both kinds of methods. The immunochromatographic procedure fulfils
      the acceptance criteria indicated by the EPA, even for sub-parts-per-billion
      concentrations.

PMID- 11467563
TI  - Immobilized fluorescent cyclodextrin on a cellulose membrane as a chemosensor for
      molecule detection.
AB  - Dansylglycine-modified cyclodextrin (DnsC4-beta-CD) was prepared as a fluorescent
      host that is capable of being immobilized on a cellulose membrane (DnsC4-beta-CD
      membrane). DnsC4-beta-CD immobilized on the cellulose membrane decreased its
      fluorescence intensity with increasing concentration of guest molecules,
      indicating that the host changes the location of the dansyl group from inside to
      outside the cyclodextrin cavity upon guest accommodation, which is similar to
      DnsC4-beta-CD in solution; thereby, the DnsC4-beta-CD membrane is useful as a
      novel chemosensor for detecting molecules. This result demonstrates that the
      cellulose membrane is useful as a practical supporting material for various
      chromophore-modified cyclodextrins.

PMID- 11467564
TI  - Sampling and Raman confocal microspectroscopic analysis of airborne particulate
      matter using poly(dimethylsiloxane) solid-phase microextraction fibers.
AB  - Commercial poly(dimethylsiloxane) (PDMS) 7-microm solid-phase microextraction
      (SPME) fibers were used for sampling and Raman spectroscopic analysis of a
      tailpipe diesel exhaust, candle smoke, cigarette smoke, and asbestos dust.
      Samples were collected via direct exposure of the SPME fiber to contaminated air.
      The mass loading for SPME fibers was varied by changing the sampling time.
      Results indicate that PDMS-coated fibers provide a simple, fast, reusable, and
      cost-effective air sampling tool for airborne particulates. The PDMS coating was
      stable; Raman bands of the PDMS coating were observed exactly at the same
      wavenumber positions before and after air sampling. Raman spectroscopic analysis
      resulted in identification of several characteristic bands allowing chemical
      speciation of particulates. The advantage of the SPME fiber is the open bed
      geometry allowing for application of various spectroscopic methods of particulate
      analysis. This paper describes the first-ever combined application of SPME
      technology with Raman confocal microspectroscopy for sampling and analysis of
      airborne particulates. Advantages of the combination of solid-phase
      microextraction and Raman microspectroscopy for airborne particulate analysis are
      discussed. Challenges associated with combined SPME sampling and Raman analysis
      of single particles are also described.

PMID- 11467565
TI  - Fibers coated with molecularly imprinted polymers for solid-phase
      microextraction.
AB  - The simplicity and flexibility of solid-phase microextraction have been combined
      with the selectivity of molecularly imprinted polymers (MIPs). Silica fibers were
      coated reproducible with a 75-microm layer of methacrylate polymer either
      nonimprinted or imprinted with clenbuterol to compare their extraction
      characteristics under various conditions. Although the template molecule could be
      removed effectively from the imprinted polymer, structural analogues of
      clenbuterol were used for evaluation. The influence of pH on the extractability
      of brombuterol was investigated. Extraction yields up to approximately 80% were
      obtained when both types of fibers were used to extract brombuterol from
      phosphate buffer (pH 7.0). In contrast, yields of about 75 and <5% were obtained
      when extraction was performed from acetonitrile with imprinted and nonimprinted
      polymers, respectively, which demonstrates the selectivity of the MIP-coated
      fiber. Time sorption profiles were measured for the extraction of brombuterol
      from buffer and acetonitrile at the 10 and 100 ng/mL level with both types of
      fibers in order to compare extraction characteristics. Equilibrium times of about
      30 and 90 min were found for the extraction of brombuterol from acetonitrile and
      buffer, respectively. The MIP-coated fibers were capable of extracting five
      structural analogues of clenbuterol from both buffer and acetonitrile, which
      suggests that the amine alcohol part of these molecules is responsible for
      interaction with the imprinted polymer. To achieve selective extraction of
      brombuterol from human urine, MIP-coated fibers were washed with acetonitrile
      after the extraction. Clean extracts and yields of approximately 45% were
      obtained, demonstrating the suitability of MIP-coated fibers for the analysis of
      biological samples.

PMID- 11467566
TI  - Detection of pesticide model compounds in ethanolic and aqueous microdroplets by
      nonlinear Raman spectroscopy.
AB  - Pesticide model compounds are detected in microdroplets by means of in situ
      nonlinear Raman spectroscopy. The chloro- and nitro-substituted aromatics are
      dissolved in ethanol as well as in water. Their vibrational spectroscopic
      fingerprint, that is, Raman bands characteristic of the functional groups
      attached to the aromatic system, is determined in bulk medium by linear Raman
      spectroscopy. As a result of the concept of group vibrations, the chosen
      compounds can be regarded as representatives for a whole class of pesticides
      containing these residues. External seeding of stimulated Raman scattering (SRS)
      is applied for the detection of these group vibrations of the pesticide model
      compounds. This technique can be utilized for in situ diagnostics and a
      noninvasive vibrational spectroscopic analysis of the chemical composition of
      microdroplets with natural or anthropogenic origin.

PMID- 11467567
TI  - Studies on the structure of water using two-dimensional near-infrared correlation
      spectroscopy and principal component analysis.
AB  - The structure of water molecules in the pure liquid state has been subjected to
      extensive research for several decades. Questions still remain unanswered,
      however, and no single model has been found capable of explaining all the
      anomalies of water. In the present study, near-infrared spectra of water in the
      temperature region 6-80 degrees C have been analyzed by use of principal
      component analysis and two-dimensional correlation spectroscopy in order to study
      the dynamic behavior of a band centered around 1,450 nm at room temperature,
      which is due to the combination of symmetric and antisymmetric O-H stretching
      modes (first overtone) of water. It has been found that the wavelengths 1,412 and
      1,491 nm account for more than 99% of the spectral variation, representing two
      major water species with weaker and stronger hydrogen bonds, respectively. A
      third species located at 1438 nm, whose concentration was relatively constant as
      a function of temperature, is also indicated. A somewhat distorted two-state
      structural model for water is suggested.

PMID- 11467568
TI  - Detection of Cryptosporidium parvum using oligonucleotide-tagged liposomes in a
      competitive assay format.
AB  - To meet the technical challenge of accurately and rapidly detecting
      Cryptosporidium parvum oocysts in environmental water, the authors developed a
      single-use visual-strip assay. The first step in the overall assay procedure
      involves extracting C. parvum's mRNA coding for heat-shock protein hsp70,
      followed by amplification using nucleic acid sequence-based amplification (NASBA)
      methodology as described previously (Baeumner, A. J.; Humiston, M.; Montagna, R.
      A.; Durst, R. A. Anal. Chem., in press). Subsequently, generated amplicons are
      hybridized with dye-entrapping liposomes bearing DNA oligonucleotides (reporter
      probes) and biotin on their surface. The liposome-amplicon complex is then
      allowed to migrate upward on a nitrocellulose membrane strip. On the
      nitrocellulose strip, antisense-reporter probes are immobilized in a capture zone
      and antibiotin antibodies are immobilized in a second zone above the capture
      zone. Depending on the presence or absence of amplicon in the sample, the
      liposomes will bind to the capture zone, or they will be caught via their biotin
      tag in the second zone. Visual detection or gray-scale densitometry allows the
      quantification of liposomes that are present in either zone. The detection limit
      of the assay was determined to be 80 fmol amplicon/test. High accuracy and an
      internal assay control is established using this competitive format, because the
      presence or absence of liposomes can be quantified in the two capture zones.

PMID- 11467569
TI  - A fluorescent receptor assay for benzodiazepines using coumarin-labeled
      desethylflumazenil as ligand.
AB  - This article describes a novel nonisotopic receptor assay for benzodiazepines
      with fluorescence detection. As labeled ligand (coumarin-labeled
      desethylflumazenil, CLDEF), a metabolite of the benzodiazepine antagonist
      flumazenil (desetheylflumazenil, Ro15-3890) has been coupled to a coumarin
      fluorophore, via a spacer. CLDEF had a Ki of 6.5 nM. To avoid the interference of
      the background fluorescence of the receptors in the measurement step, the bound
      CLDEF was dissociated from the receptors after the filtration step. This
      dissociation was achieved by incubating the CLDEF-bound to the receptors on the
      filters-with a weakly acetate buffer. The second filtrates then contained the
      previously bound CLDEF, which was then quantitated with a RP-HPLC system with a
      fluorescence detector. The results with a fluorescent receptor assay were very
      similar to those with a radioreceptor assay, in that the IC50 values of lorazepam
      were 7.2 +/- 0.5 and 6.6 +/- 0.7 nM, respectively.

PMID- 11467570
TI  - Simultaneous determination of mono-, di-, and tributyltin in sediments by isotope
      dilution analysis using gas chromatography--ICPMS.
AB  - A mixed spike containing 119Sn-enriched monobutyltin (MBT), dibutyltin (DBT), and
      tributyltin (TBT) was prepared by direct butylation of 119Sn-enriched tin metal
      using a 1:3 molar excess of butyl chloride with iodide and triethylamine as
      catalysts. The isotopic composition of the different tin species in the spike
      solution was determined by gas chromatography- ICPMS after aqueous ethylation
      using sodium tetraethylborate. Reverse isotope dilution analysis was used for the
      characterization of the spike by means of natural MBT, DBT, and TBT standards. No
      species transformation was evident during derivatization from the reverse isotope
      dilution experiments based on the measured isotope ratios both before and after
      spiking. The mixed spike was applied to the simultaneous analysis of MBT, DBT,
      and TBT in certified reference materials, PACS-2 and CRM 646, with satisfactory
      results.

PMID- 11467571
TI  - Identification of volatile selenium compounds produced in the hydride generation
      system from organoselenium compounds.
AB  - We report a novel aqueous derivatization of selenomethionine (Semet),
      selenoethionine (Seet) and trimethylselenonium ion (TmSe) by NaBH4 and HCI to
      volatile selenium species, namely, diethyldiselenide (DeDSe), dimethyldiselenide
      (DMDSe), dimethylselenide (DmSe) and ethylhydrogenselenide (ESeH), in the hydride
      generation (HG) system. The volatile selenium compounds produced in the HG system
      were on-line trapped and concentrated in a U-tube that was immersed in the liquid
      nitrogen trap. The trapped volatile Se compounds were volatilized at 80 degrees C
      in a water bath, and 50-500 microL of volatile gas was injected into the GC/AED
      and GC/MS, respectively. It has been established that DmSe, DmDSe, and DeDSe are
      the predominant Se compounds that are produced in the HG system from TmSe, Semet,
      and Seet, respectively, followed by ESeH from Seet. Analytical methods previously
      employed have stated that these compounds are inactive in the HG system. Prior
      decomposition of Semet, Seet, and TmSe to selenous acid is essential before HG.
      To the best of our knowledge, current findings for the production and
      identification of volatile selenium compounds in the HG system are new and
      different from existing reports; hence, direct estimation of Semet, Seet, and
      TmSe is possible when coupling with a HG system using a suitable Se-specific
      detector.

PMID- 11467572
TI  - Sensitive and selective flow injection analysis of hydrogen sulfite/sulfur
      dioxide by fluorescence detection with and without membrane separation by gas
      diffusion.
AB  - Highly sensitive and selective FIA flow injection analysis procedures for the
      determination of sulfite/hydrogen sulfite/sulfur dioxide were developed on the
      basis of an in situ-generated o-phthalaldehyde (OPA)/ammonium reagent and
      fluorescence detection. The highest sensitivity was achieved at an excitation
      wavelength of 330 nm, an emission wavelength of 390 nm, and at pH 6.5. Sulfite
      concentrations between 2.5 nM and 5 microM can be determined with relative
      standard deviations between 10.5 and 1.0% (n = 5, confidence level alpha = 0.05)
      by utilization of a reagent that contains 0.2 mM OPA and 0.4 M NH4Cl in 50 mM
      potassium phosphate buffer. A concentration of 0.1 mM sulfite can be selectively
      detected in the presence of thiosulfate, thioglycolate, tetrathionate, cysteine,
      and ascorbate. The fluorometric sulfite detection was combined with a membrane
      gas diffusion step to improve the selectivity with respect to nonvolatile
      fluorescing substances. The total sulfite content can be quantitatively separated
      as sulfur dioxide into an acceptor solution before its flow detection. Between 40
      nM and 0.1 mM sulfite can be determined. After 1,000-fold dilution, the total
      sulfite content can be determined in white and red wines.

PMID- 11467573
TI  - A method for filling complex polymeric microfluidic devices and arrays.
AB  - This paper describes an improved method for filling microfluidic structures with
      aqueous solutions. The method, channel outgas technique (COT), is based on a
      filling procedure carried out at reduced pressures. This procedure is compared
      with previously reported methods in which microfluidic channels are filled either
      by using capillary forces or by applying a pressure gradient at one or more empty
      reservoirs. The technique has proven to be > 90% effective in eliminating the
      formation of bubbles within microfluidic networks. It can be applied to many
      devices, including those containing PDMS-terminated channel features, a single
      channel inlet, and three-dimensional arrays.

PMID- 11467574
TI  - Impact of the present funding imbalance.

PMID- 11467575
TI  - Living cell microarray.

PMID- 11467576
TI  - Evidence for electroosmotic perfusion.

PMID- 11467579
TI  - Individual hairpin dynamics.

PMID- 11467578
TI  - Theory for a SNEM.

PMID- 11467577
TI  - A lineup in the microchannel.

PMID- 11467580
TI  - Assessing carcinogen exposure with MS.

PMID- 11467582
TI  - Extreme electrochemistry.

PMID- 11467581
TI  - Detecting living cryptosporidium.

PMID- 11467583
TI  - An "udder" milk safety test.

PMID- 11467584
TI  - Rainbow stars. A spectrum of possibilities.

PMID- 11467585
TI  - FTIR images.

PMID- 11467586
TI  - Extracting information from the literature by text mining.

PMID- 11467587
TI  - Proteomics systems emerge.

PMID- 11467588
TI  - The emergence of feline pancreatitis.

PMID- 11467589
TI  - Comparison of the sensitivity of different diagnostic tests for pancreatitis in
      cats.
AB  - The objective of this study was to compare the sensitivity of different
      diagnostic tests for pancreatitis in cats. Twenty-one cats with confirmed
      pancreatitis were evaluated at the Small Animal Clinic of the School of
      Veterinary Medicine in Hannover, Germany, between September 1997 and January
      1999. Clinical signs of affected cats were nonspecific, with 95% of the cats
      showing anorexia and 86% lethargy. Also, hematologic and biochemical
      abnormalities of affected cats were nonspecific. Serum feline trypsin-like
      immunoreactivity (fTLI) in these 21 cats with pancreatitis was 127.5 +/- 109.5
      microg/L (mean +/- SD; range, 24-500 microg/L). Fourteen of the 21 cats with
      pancreatitis had complicating conditions. Their serum fTLI was 153.9 +/- 124.3
      microg/L (mean +/- SD; range, 29 500 microg/L). In this study, abdominal
      ultrasound showed a sensitivity for pancreatitis of 24%, and abdominal computed
      tomography had a sensitivity of 20%. Serum fTLI had a sensitivity between 86%
      when a cut-off value of 49 microg/L was used (upper limit of the control range)
      and 33% when a cut-off value of 100 microg/L was used. We conclude that in this
      group of cats with pancreatitis, measurement of serum fTLI was the most sensitive
      diagnostic test of those evaluated. Abdominal ultrasound, however, may be a
      valuable diagnostic tool in some cats with pancreatitis.

PMID- 11467590
TI  - Cellular proliferation in tumors: a review of methods, interpretation, and
      clinical applications.
AB  - Cellular proliferation with altered control is one of the 1st characteristics of
      a neoplastic cell population. Although tumor growth reflects both tumor cell
      replication and cell loss (opposing growth and antigrowth factors), most studies
      published in veterinary literature used immunohistochemistry (proliferating cell
      nuclear antigen [PCNA]; Ki-67 [MIB-1]) or staining for argyrophilic nucleolar
      organizer regions (AgNORs) to measure proliferation. These studies have appeared
      in the veterinary literature for more than a decade, describing associations
      between proliferation indices and histologic grade, biological behavior, and
      clinical outcome for some tumor types but no clinically relevant associations for
      other tumors. The results of these studies are summarized here. Methods for
      evaluation of the numerous regulatory proteins that direct the cell throughout
      its cycle are now available and should allow more precise identification of
      cellular aberrations in cancer.

PMID- 11467591
TI  - Interrelations of organism prevalence, specimen collection method, and host age,
      sex, and breed among 8,354 canine urinary tract infections (1969-1995).
AB  - Selected information was compiled from canine urinalyses and urine cultures
      conducted between January 1969 and December 1995. Eight thousand three hundred
      fifty-four microbial isolates (bacteria and fungi) included 4,873 isolates from
      females and 3,481 from males. Ten bacterial genera accounted for 96.3% of the
      urinary isolates, including Escherichia coli (44.1%), Staphylococcus spp.
      (11.6%), Proteus spp. (9.3%), Klebsiella spp. (9.1%), Enterococcus spp. (8.0%),
      and Streptococcus spp. (5.4%) as the 6 most common isolates in both genders of
      dogs. Among these 6 genera, female dogs were generally predisposed over males,
      although males had more urinary tract infections (UTIs) caused by Klebsiella spp.
      Distributions of ages at UTI diagnosis tended to be similar between genders.
      Infection with a single microbial species was responsible for >72% of UTIs in
      both genders. Among females, 40 breeds and a mixed-breed group represented 90.2%
      of all positive urine cultures, 88.4% of the individual dogs with UTIs. and 88.2%
      of the microbial isolations. Among males, these same 41 breed groups represented
      87.9% of all positive urine cultures, 87.6% of the individual dogs, and 88.2% of
      the microbial isolations.

PMID- 11467592
TI  - Evaluation of a discontinuous treatment protocol (VELCAP-S) for canine lymphoma.
AB  - Eighty-two dogs with lymphoma received a single 15-week course of chemotherapy,
      after which treatment was ceased until relapse. Fifty-six dogs (68%) achieved
      complete remission for a median 1st remission duration of 20 weeks. Forty-eight
      dogs relapsed, of which 30 repeated the induction cycle. In 22 of these dogs, 1st
      remission had been short, and they received maintenance chemotherapy; the other 8
      dogs received 2 or 3 cycles of induction chemotherapy. Second remission rate for
      these 30 dogs was 87% (26 dogs). Overall disease control for the 38 dogs that
      remained on protocol was 44 weeks, which was not markedly shorter than for dogs
      treated with a previously reported protocol in which maintenance chemotherapy was
      instituted in all dogs after an identical 1st induction (VELCAP-L). Dogs that
      were febrile and dogs that were dyspneic were less likely to achieve a complete
      remission to induction chemotherapy. Of dogs that achieved a complete remission,
      those that were thrombocytopenic at entry had a shorter 1st remission, and dogs
      that were anorexic at entry had shorter overall disease control. There was a
      correlation between 1st remission duration and length of any subsequent remission
      obtained. The incidence of toxicity was high, particularly after the combination
      of doxorubicin and vincristine. Dose reductions because of toxicity did not
      markedly reduce remission duration. We conclude that discontinuous chemotherapy
      may reduce patient visits in a small number of patients because of long-term
      disease control. Delaying maintenance chemotherapy until after 2nd remission is
      achieved does not markedly affect overall disease control.

PMID- 11467593
TI  - Recombinant bactericidal/permeability-increasing protein (rBPI21) for treatment
      of parvovirus enteritis: a randomized, double-blinded, placebo-controlled trial.
AB  - We evaluated the ability of an antimicrobial and endotoxin-neutralizing agent,
      the recombinant amino terminal fragment of bactericidal permeability-increasing
      protein (rBPI21), to decrease plasma endotoxin concentration and severity of
      clinical signs of canine parvovirus and to improve survival. This randomized,
      double-blinded, placebo-controlled clinical trial included 40 client-owned dogs
      and 9 normal puppies from a closed research colony. Dogs weighing >5 kg (11 lb)
      with fecal antigen-confirmed parvovirus and clinical signs of vomiting and
      diarrhea were randomly assigned to receive placebo or rBPI21 infusion over 6
      hours. Plasma endotoxin concentration was measured at 0, 3, and 6 hours of
      infusion. Owners chose continued medical care with either the Veterinary Hospital
      of the University of Pennsylvania Internal Medicine Service or a local
      veterinarian. Telephone follow-up was conducted at 14 days. Surviving dogs were
      reevaluated at >30 days (recovered group), at which time plasma samples for
      measurement of endotoxin concentration were obtained. Plasma endotoxin
      concentrations were significantly higher in dogs with parvovirus than in normal
      or recovered dogs. Despite 90% survival, the rBPI21 treatment did not have a
      significant effect on outcome, duration of hospitalization, or plasma endotoxin
      concentrations. Treatment in a tertiary care hospital, however, significantly
      improved survival but resulted in a significantly increased duration of
      hospitalization. Endotoxemia occurs in dogs with parvovirus enteritis, but rBPI21
      is not associated with improved survival.

PMID- 11467594
TI  - Cystinuria in the dog: clinical studies during 14 years of medical treatment.
AB  - The purpose of this study was to summarize 14 years of clinical experience with
      medical treatment of 88 cystinuric dogs. Of special interest was evaluation of
      recurrence rate of cystine uroliths and adverse effects during long-term
      tiopronin treatment. Twenty-six different breeds were recognized, and the most
      common breeds were Dachshunds, Tibetan Spaniels, and Basset Hounds. In 76 of 88
      treated dogs (86%), re-formation of cystine uroliths was prevented. Recurrence
      rate of cystine uroliths changed from 7 months before to 18 months during
      tiopronin treatment. On 28 occasions, bladder stones were found, and in about 60%
      of the dogs, the uroliths dissolved. Quantitative measurement of the urinary
      excretion of cystine showed a significantly (P < .03) higher excretion of cystine
      in dogs with recurrent urolith formation than in dogs with only 1 urolith
      episode. Another finding was a significant (P = .02) decrease in urinary cystine
      excretion in older (>5 years) than in younger (<5 years) dogs. Adverse effects
      were found in 11 dogs, and the most severe signs were aggressiveness and
      myopathy. All signs disappeared when tiopronin treatment was stopped. In
      conclusion, this study emphasizes the importance of an individual strategy for
      lifelong treatment of cystinuria. In addition to increasing water intake,
      chemical modification of the cysteine molecule into a more soluble form by means
      of tiopronin is useful. In dogs with re-formed cystine uroliths, dissolution may
      be induced by increasing the tiopronin dosage to 40 mg/kg body weight per day. In
      dogs with a low urolith recurrence rate and low urinary cystine excretion, the
      tiopronin dosage may be decreased or treatment discontinued.

PMID- 11467595
TI  - Relationship between plasma iohexol clearance and urinary exogenous creatinine
      clearance in dogs.
AB  - The objective of this study was to determine if plasma iohexol clearance,
      computed by a 1-compartment model defined by 3 plasma samples. was an accurate
      measure of glomerular filtration rate (GFR) in dogs. Twenty-two adult Beagle dogs
      of both genders were studied. Ten dogs had intact kidneys, and 12 dogs had
      surgically reduced renal mass. A bolus injection of iohexol was made, and blood
      was obtained for plasma iohexol assay after 120, 180, and 240 minutes. Plasma was
      analyzed for iohexol concentration by means of 3 assay methods: chemical, high
      performance liquid chromatography (HPLC), and inductively coupled plasma emission
      spectroscopy (ICP). Urinary clearance of exogenous creatinine was used to measure
      GFR for three 30-minute periods occurring between 150 and 240 minutes after
      iohexol injection. Plasma clearance of iohexol and renal clearance of creatinine
      were compared by linear regression analysis and by limits of agreement
      techniques. Plasma iohexol clearance and urinary exogenous creatinine clearance
      were significantly correlated (chemical R2 = .90; HPLC R2 = .96; and ICP R2 =
      .96). The 1-compartment iohexol clearance:exogenous creatinine clearance ratios
      were 1.04 +/- 0.17, 1.05 +/- 0.14, and 1.10 +/- 0.15 for the chemical, HPLC, and
      ICP methods of assay, respectively, indicating that plasma iohexol clearance
      slightly overestimated GFR. Assuming a +/- 2 standard deviation interval for
      error, corrected plasma iohexol clearance measured GFR with +/-34% accuracy for
      the chemical, +/-26% accuracy for the HPLC, and +/-27% accuracy for the ICP
      method. These results indicate that plasma iohexol clearance should have utility
      for detection of renal dysfunction earlier in the course of progressive renal
      disease than is possible with measurement of plasma creatinine or urea
      concentrations.

PMID- 11467596
TI  - The roles of Clostridium difficile and enterotoxigenic Clostridium perfringens in
      diarrhea in dogs.
AB  - In this prospective study, feces of dogs with diarrhea were compared with feces
      of normal dogs for the presence of Clostridium difficile, C difficile toxins A
      and B, C perfringens, and C perfingens enterotoxin (CPE). C difficile toxins A,
      B, or both were present in feces of 18 of 87 (21%) dogs with diarrhea and 4 of 55
      (7%) normal dogs (P = 0.03), whereas CPE was present in the feces of 24 of 87
      (28%) dogs with diarrhea and 3 of 55 (5%) normal dogs (P = 0.01). C difficile was
      isolated from 2 of 87 (2%) dogs with diarrhea but was not isolated from the feces
      of 55 normal dogs, possibly because of poor survival of the organism in fecal
      samples. C perfringens was isolated from the feces of 23 of 24 (96%) CPE-positive
      dogs with diarrhea, 52 of 63 (83%) CPE-negative dogs with diarrhea, and 39 of 55
      (71%) CPE-negative dogs with normal feces. No correlation was found between C
      perfringens spore number and the presence of CPE.

PMID- 11467597
TI  - Oral chromium picolinate and control of glycemia in insulin-treated diabetic
      dogs.
AB  - Chromium is an essential dietary trace mineral involved in carbohydrate and lipid
      metabolism. Chromium is required for cellular uptake of glucose, and chromium
      deficiency causes insulin resistance. Chromium supplementation may improve
      insulin sensitivity and has been used as adjunct treatment of diabetes mellitus
      in humans. In this study, 13 dogs with naturally acquired diabetes mellitus were
      treated with insulin for 3 months, then with insulin and chromium picolinate for
      3 months. Dogs weighing <15 kg (33 lb: n = 9) were administered 200 microg of
      chromium picolinate PO once daily for I month, then 200 microg of chromium
      picolinate twice daily for 2 months. Dogs weighing >15 kg (n = 4) received 200
      microg of chromium picolinate once daily for 2 weeks, then 200 microg twice daily
      for 2 weeks, then 400 microg twice daily for 2 months. Type of insulin, frequency
      of insulin administration, and diet were kept constant, and insulin dosage was
      adjusted, as needed, to maintain optimal control of glycemia. Mean body weight,
      daily insulin dosage, daily caloric intake, 10-hour mean blood glucose
      concentration, blood glycated hemoglobin concentration, and serum fructosamine
      concentration were not markedly different when dogs were treated with insulin and
      chromium picolinate, compared with insulin alone. Adverse effects were not
      identified with chromium picolinate administration. Results of this study suggest
      that, at a dosage range of 20-60 microg/kg/d, chromium picolinate caused no
      beneficial or harmful effects in insulin-treated diabetic dogs.

PMID- 11467598
TI  - Diagnostic validity of electroencephalography in equine intracranial disorders.
AB  - Electroencephalography (EEG) is a valuable diagnostic test to identify functional
      disturbances in brain activity. The purpose of this study was to assess the
      validity of EEG as a diagnostic indicator of intracranial diseases in horses. The
      validity of EEG was estimated by comparing clinical, clinicopathologic, and
      histopathologic findings to EEG findings in 20 horses examined for seizures.
      collapse, or abnormal behavior between 1984 and 1997. A bipolar left-to-right,
      back-to-front montage and a bipolar circular montage were recorded from sedated
      (4) and anesthetized (16) horses. Visual and semiquantitative masked analysis of
      EEG recording Ist was validated on 10 horses presented for problems other than
      intracranial diseases. EEG pattern was normal in 7 of the 20 clinically affected
      horses. Abnormal EEG patterns included high-voltage slow waves and discrete
      paroxysmal activity with or without generalized activity in 13 horses.
      Histopathologic diagnoses in 10 horses included meningoencephalitis, neuronal
      necrosis, congenital anomalies. cerebral edema. and abscess. All of these horses
      had abnormal EEG patterns (sensitivity, 100%) with a positive neuroanatomic
      correlation in 7 animals. Localization of histopathologic and EEG abnormalities
      did not correlate in 15% of the horses (3/20). The cause of neurologic signs
      could not be explained at postmortem examination in 10 animals and the EEG
      pattern was normal in 7 of these horses (specificity, 70%). In conclusion, equine
      EEG was a sensitive tool in the diagnosis of intracranial disorders.

PMID- 11467599
TI  - Ability of hematologic and serum biochemical variables to differentiate gram
      negative and gram-positive mastitis in dairy cows.
AB  - Medical records of 142 dairy cows with clinical mastitis were examined to
      determine whether hematologic or serum biochemical results could be used to
      distinguish between mastitis episodes caused by gram-negative bacteria (n = 78)
      from those caused by gram-positive bacteria (n = 64). Signalment, historic
      information, hematologic and serum biochemical results, milk culture results, and
      outcome (discharged from hospital or died) were obtained from the medical
      records. Cows with gram-negative mastitis had significantly (P < .01) lower blood
      leukocyte, segmented neutrophil, monocyte, and lymphocyte counts and had higher
      blood hemoglobin concentrations and hematocrits than did cows with gram-positive
      mastitis. Serum urea nitrogen was the only serum biochemical result associated
      with pathogen type, and it was higher in cows with gram-negative mastitis than in
      those with gram-positive mastitis. Mortality rate (25% overall) did not differ
      between groups. Logistic regression indicated that routine hematologic analysis
      (segmented neutrophil count, monocyte count, and hemoglobin concentration) was an
      accurate predictor of gram-negative mastitis, with a sensitivity of .93, a
      specificity of .89, and an overall accuracy of 91%. The values for sensitivity
      and specificity were higher than those previously reported for clinical tests
      differentiating mastitis episodes caused by gram-negative bacteria from those
      caused by gram-positive bacteria. Our results indicate that routine hematologic
      analysis is useful for predicting pathogen type in dairy cows with clinical
      mastitis, thereby facilitating treatment decisions.

PMID- 11467600
TI  - Endoscopic findings of the gastric antrum and pylorus in horses: 162 cases (1996
      2000).
AB  - Medical records and endoscopy images were examined for 209 horses that had
      gastroscopic examinations performed with a 2.5- or 3-m-long endoscope by one of
      the authors (MJM) during a 4-year period (1996-2000). The antrum and pylorus were
      viewed in 162 horses, and the duodenum was viewed in 94 horses. Of these 162
      horses, the gastric squamous mucosa was seen in 157 horses and 50% or more of the
      glandular mucosa of the body of the stomach was seen in 156 horses. Erosions or
      ulcers were seen in the gastric squamous mucosa in 91 (58%) horses. Erosions or
      ulcers were seen in the glandular mucosa of the body of the stomach in only 8% of
      the horses. Lesions consisting of erosion or ulceration were seen in the antrum
      or pylorus in 94 (58%) horses. Lesions consisting of hyperemia and a rough or
      "bumpy" appearance were seen in the mucosa of the duodenum of 16 horses. An
      association between the presence of lesions in the squamous mucosa and the
      presence of lesions in the mucosa of the antrum/pylorus was examined by Fisher's
      exact test, and the linear association of lesion severity scores between the
      squamous mucosa and the mucosa of the antrum/pylorus was tested using a Monte
      Carlo estimate for linear-by-linear association. There was no association (P =
      .88) between these sites for presence of lesions or lesion severity scores.
      Similarly, there was no association between scores for the glandular mucosa in
      the gastric body and those in the antrum/pylorus. Because of the high prevalence
      of lesions in the antrum and pylorus of the stomachs of adult horses examined in
      a hospital setting, the entire stomach should be viewed during a gastroscopic
      examination.

PMID- 11467601
TI  - Resolution of paraneoplastic leukocytosis and hypertrophic osteopathy after
      resection of a renal transitional cell carcinoma producing granulocyte-macrophage
      colony-stimulating factor in a young Bull Terrier.

PMID- 11467602
TI  - Evidence for transmission of Halicephalobus deletrix (H gingivalis) from dam to
      foal.

PMID- 11467604
TI  - FMD: movement restrictions eased in infected areas.

PMID- 11467603
TI  - Hydroxyurea for treatment of polycythemia secondary to right-to-left shunting
      patent ductus arteriosus in 4 dogs.
AB  - Four adult dogs with polycythemia secondary to reversed patent ductus arteriosus
      (rPDA) were treated with hydroxyurea, a myelosuppressive agent, for 6-22 months.
      Regardless of initial hematocrit, clinical signs attributed to the presence of
      polycythemia improved with hydroxyurea treatment. Chronic hydroxyurea therapy (40
      50 mg/kg PO q48h) was well tolerated in this group of animals; mild, clinically
      silent thrombocytopenia and leukopenia were detected in some animals but resolved
      with decreased dosage or dose frequency. Chronic hydroxyurea therapy may provide
      an alternative to repeated phlebotomy for therapy of polycythemia secondary to
      rPDA.

PMID- 11467605
TI  - Modelling future manpower requirements.

PMID- 11467606
TI  - Management of horses showing stereotypic behaviour, owner perception and the
      implications for welfare.
AB  - A telephone survey was conducted of 100 racing stables, 100 riding schools and
      100 competition establishments (8,427 horses in total) to determine what
      management practices were being applied to horses showing stereotypic behaviour,
      and to determine the underlying reasons for them by assessing the perceptions and
      opinions of the people working with the horses. The results indicated that horse
      owners are concerned about stereotypic behaviour, first, because it reduces the
      performance of the animal (31, 30 and 27 per cent of the owners of racing
      stables, riding schools and competition establishments respectively), secondly,
      because it has adverse clinical effects on the horse (52, 55 and 56 per cent),
      and thirdly, because it reduces the monetary value of the animal (45, 59 and 31
      per cent). The belief that these behaviours are learnt or copied also affects the
      management of affected horses: they are not allowed on to the premises by 4, 32
      and 17 per cent of owners of racing stables, riding schools and competition
      establishments, respectively; attempts are made to remove the causal factors of
      the stereotypy by 35, 43 and 36 per cent; the behaviours are physically prevented
      by 77, 67 and 79 per cent, and the affected horses are kept separate from other
      horses by 39, 30 and 48 per cent.

PMID- 11467607
TI  - Comparison of thelotomy and theloscopic triangulation for the treatment of distal
      teat obstructions in dairy cows--a retrospective study (1994-1998).
AB  - The medical records of 56 cows suffering from teat obstructions in the area of
      the rosette of Furstenberg were reviewed; 22 were treated by thelotomy and 34 by
      theloscopic triangulation and the long-term results were reviewed by telephone
      conversations with the owners up to four years after the surgery. The milk flow
      at the fourth milking session after surgery was significantly better in the cows
      treated by theloscopy and, as a result, fewer of these cows required the teat
      sphinder to be cut. The cows treated by theloscopy also stayed in hospital for a
      significantly shorter period and suffered fewer episodes of mastitis.

PMID- 11467608
TI  - Phaeochromocytoma in two coatimundi (Nasua nasua).
AB  - Two unrelated coatimundi (Nasua nasua) had bilaterally enlarged adrenal glands at
      necropsy, and sections of the glands from both animals had histopathological
      features consistent with neoplasia. They were differentiated from an adrenal
      cortical tumour on the basis of their light microscopical morphology,
      immunoperoxidase staining and electron microscopic studies and a final diagnosis
      of phaeochromocytoma was made. To the authors' knowledge, these are the first
      reported cases of phaeochromocytoma in coatimundi.

PMID- 11467609
TI  - First confirmed canine case of Ehrlichia canis infection in Japan.
AB  - An 11-year-old castrated Pekinese dog that had been moved from Indonesia to Japan
      eight years previously was diagnosed with an Ehrlichia canis infection by
      haematological characteristics (normocytic anaemia, mild thrombocytopenia and
      hypergammaglobulinaemia) and serological findings (antibody titre to E canis
      1:3,200 or more). The dog did not respond to treatment with tetracycline and died
      from renal failure. The diagnosis was confirmed postmortem by pathological
      evaluation and polymerase chain reaction (PCR) followed by sequencing of the 16S
      rRNA gene. Typical morulae of Ehrlichia were detected in the cytoplasm of
      macrophages in spleen tissue by immunohistological staining. Ehrlichia-like
      organisms were also detected in the spleen by electron microscopy. E canis
      specific PCR analysis of DNA extracted from the spleen gave a positive signal,
      and sequence analysis of the fragment revealed that it was identical to part of
      the 16s rRNA gene of E canis. The dog was the first confirmed clinical case of E
      canis infection in Japan.

PMID- 11467610
TI  - Use of transrectal ultrasonography to aid diagnosis of small colon strangulation
      in two horses.

PMID- 11467611
TI  - In vitro and in vivo efficacy of extracts of Artemisia verlotorum against
      Psoroptes cuniculi.

PMID- 11467612
TI  - Plasma lipids and cholesterol profiles of dairy cattle for monitoring herd health
      status in the central Himalayas.

PMID- 11467613
TI  - Grass sickness with atypical presentation in a young zebra.

PMID- 11467614
TI  - Fatal Babesia gibsoni infection in a dog from Spain.

PMID- 11467615
TI  - FMD control strategies.

PMID- 11467616
TI  - Pen-side test for investigating FMD.

PMID- 11467617
TI  - Renal transplants in cats.

PMID- 11467618
TI  - Renal transplants in cats.

PMID- 11467619
TI  - The Charleston MRCP experience: a tiny step in the right direction.

PMID- 11467620
TI  - Predicting the severity of acute pancreatitis: is it time to concentrate on the
      hematocrit?

PMID- 11467621
TI  - Doctor-patient communication after endoscopy: drowning in information, starving
      for knowledge?

PMID- 11467622
TI  - Hepatic Encephalopathy.
AB  - 1. Acute Encephalopathy in Cirrhosis A. GENERAL MEASURES. Tracheal intubation in
      patients with deep encephalopathy should be considered. A nasogastric tube is
      placed for patients in deep encephalopathy. Avoid sedatives whenever possible.
      Correction of the precipitating factor is the most important measure. B. SPECIFIC
      MEASURES i. Nutrition. In case of deep encephalopathy, oral intake is withheld
      for 24-48 h and i.v. glucose is provided until improvement. Enteral nutrition can
      be started if the patient appears unable to eat after this period. Protein intake
      begins at a dose of 0.5 g/kg/day, with progressive increase to 1-1.5 g/kg/day.
      ii. Lactulose is administered via enema or nasogastric tube in deep
      encephalopathy. The oral route is optimized by dosing every hour until stool
      evacuation appears. Lactulose can be replaced by oral neomycin. iii. Flumazenil
      may be used in selected cases of suspected benzodiazepine use. 2. Chronic
      Encephalopathy in Cirrhosis i. Avoidance and prevention of precipitating factors,
      including the institution of prophylactic measures. ii. Nutrition. Improve
      protein intake by feeding dairy products and vegetable-based diets. Oral branched
      chain amino acids can be considered for individuals intolerant of all protein.
      iii. Lactulose. Dosing aims at two to three soft bowel movements per day.
      Antibiotics are reserved for patients who respond poorly to disaccharides or who
      do not exhibit diarrhea or acidification of the stool. Chronic antibiotic use
      (neomycin, metronidazole) requires careful renal, neurological, and/or otological
      monitoring. iv. Refer for liver transplantation in appropriate candidates. For
      problematic encephalopathy (nonresponsive to therapy), consider imaging of
      splanchnic vessels to identify large spontaneous portal-systemic shunts
      potentially amenable to radiological occlusion. In addition, consider the
      combination of lactulose and neomycin, addition of oral zinc, and invasive
      approaches, such as occlusion of TIPS or surgical shunts, if present. Minimal or
      Subclinical Encephalopathy Treatment can be instituted in selected cases. The
      most characteristic neuropsychological deficits in patients with cirrhosis are in
      motor and attentional skills (60). Although these may impact the ability to
      perform daily activities, many subjects can compensate for these defects. Recent
      studies suggest a small but significant impact of these abnormalities on
      patients' quality of life (61), including difficulties with sleep (62). In
      patients with significant deficits or complaints, a therapeutic program based on
      dietary manipulations and/or nonabsorbable disaccharides may be tried.
      Benzodiazepines should not be used for patients with sleep difficulties.

PMID- 11467623
TI  - Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease:
      current and future perspectives.
AB  - Crohn's disease and ulcerative colitis are two idiopathic inflammatory disorders
      of the GI tract. Manifestations of disease can be severe and lead to long term
      therapy with a variety of medications and/or surgery. Standard medical therapy
      consists of agents that either treat suppurative complications or modulate the
      inflammatory cascade in a nonspecific manner. Many specific chemokine and
      cytokine effectors that promote intestinal inflammation have been identified.
      Such work has led to experimental clinical trials with a variety of cytokine
      antagonists. Compounds directed against one such cytokine, tumor necrosis factor
      alpha (TNF), have demonstrated the greatest clinical efficacy to date. This is
      consistent with scientific observations that suggest a central role for TNF in
      the inflammatory cascade. Infliximab is a chimeric monoclonal antibody against
      TNF that has been demonstrated to be effective for the treatment of Crohn's
      disease. Infliximab is Food and Drug Administration approved for the treatment of
      Crohn's disease. There exist several other TNF antagonists in various phases of
      investigation, including the monoclonal antibody CDP 571, the fusion peptide
      etanercept, the phosphodiesterase inhibitor oxpentifylline, and thalidomide. The
      clinical efficacy of these agents and the role of TNF in the pathogenesis of
      inflammatory bowel disease is reviewed.

PMID- 11467624
TI  - Quality of life in patients with endoscopy-negative heartburn: reliability and
      sensitivity of disease-specific instruments.
AB  - OBJECTIVES: Endoscopy-negative gastroesophageal reflux disease (GERD) lacks
      objective markers of disease severity. Evaluation of therapies for GERD must
      therefore rely on subjective measures, including patient self-report
      questionnaires, to measure the clinical effectiveness of therapeutic
      interventions. We aimed to evaluate the previously validated Gastrointestinal
      Symptoms Rating Scale (GSRS) and the Quality of Life in Reflux and Dyspepsia
      (QOLRAD) questionnaires for reliability and responsiveness to change over time.
      METHODS: Patients (n = 1143) with heartburn, but no esophagitis included in a
      randomized clinical trial assessing the effectiveness of active treatment with
      proton pump inhibitors over 4 wk were evaluated. RESULTS: The test-retest
      reliability of both questionnaires over time was good to excellent (GSRS 0.53
      0.69; QOLRAD 0.65-0.76), as was the responsiveness estimated by standardized
      response means (GSRS reflux dimension, -1.43; QOLRAD 0.81-1.43) and effect sizes
      (GRSR reflux dimension, -1.74; QOLRAD 0.82-1.56). The relationship between
      improvement in the GSRS reflux dimension score and the amount of clinical benefit
      as estimated by the patients themselves (based on the Overall Treatment
      Evaluation) suggested a minimally clinical relevant change is 0.5 on the seven
      graded scales applied. The importance rating indicated that an important change
      in the GSRS reflux dimension and the QOLRAD dimensions is equivalent to 1.0, and
      a very important change to 1.5. CONCLUSIONS: The GSRS and QOLRAD are valid
      questionnaires that are reliable and sensitive to change. Both questionnaires
      should be suitable for use in clinical trials of therapeutic interventions for
      patients with heartburn.

PMID- 11467625
TI  - Use of a simple symptom questionnaire to predict Barrett's esophagus in patients
      with symptoms of gastroesophageal reflux.
AB  - OBJECTIVE: Accurately predicting Barrett's esophagus (BE) in patients with
      gastroesophageal reflux disease (GERD) is difficult. Using logistic regression
      analysis of symptom questionnaire scores we created a model to predict the
      presence of BE. METHODS: We conducted a logistic regression analysis of symptom
      data collected prospectively on 517 GERD patients and created a prediction model
      based on patient gender, age, ethnicity, and symptom severity. RESULTS: There
      were 337 (65%) males and 180 (35%) females, of whom 99 (19%) had Barrett's
      esophagus (BE). Multiple logistic regression analysis was performed to determine
      the predictive ability of gender, age, and ethnicity along with symptoms of
      heartburn, nocturnal pain, odynophagia, presence of belching, dysphagia, relief
      of symptoms with food, and nausea. The only significant predictors (at the 0.05
      level) were male gender, heartburn, nocturnal pain, and odynophagia (all with
      positive effects on the presence of BE) and dysphagia (which had a negative
      effect). A nomogram was produced to show the effect of a given predictor on the
      probability of having BE in the context of the effects of the other predictors,
      and to estimate the probability of having BE for a given individual. The mean
      score (+/-SD) for the BE patients in our sample was 397.4+/-46.2 with a range of
      292-530. For the patients without BE, the mean score (+/-SD) was 351.3+/-60.3
      with a range of 190 - 528 (p < 0.001). If screening for BE is performed at a
      score of 375 or more, our model would have a specificity of 63% with a
      sensitivity of 77% (95% CI 61-86% given the 63% specificity). CONCLUSIONS: By
      asking seven questions about symptom severity, clinicians may be able to assign a
      probability to the presence of BE, and thus, determine the need for endoscopy in
      GERD patients.

PMID- 11467626
TI  - Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal
      cancer.
AB  - OBJECTIVE: Gastroesophageal reflux disease (GERD) is a proposed risk factor for
      developing laryngeal and pharyngeal cancers. No controlled study has examined
      this association. METHODS: A case-control-study was performed using the
      computerized hospitalization and outpatient databases of the US Department of
      Veterans Affairs. All patients, who were veterans, had been identified as being
      hospitalized with laryngeal or pharyngeal during 1991 to 1997. In addition, all
      persons diagnosed with laryngeal or pharyngeal cancer in 1999 in the outpatient
      files were identified. From the same patient populations, four nonmatched control
      subjects were randomly assigned for each case. The medical history for cases and
      controls was retrospectively searched for GERD diagnoses, tobacco use, and
      alcohol dependence. Multivariable logistic regression analyses were performed to
      assess the risk factors for laryngeal and pharyngeal cancers. RESULTS: A total of
      8,228 hospitalized patients with laryngeal cancers and 1,912 with pharyngeal
      cancers were compared to 32,912 and 7,648 hospitalized controls, while 9,292
      outpatients with laryngeal cancer and 2,769 outpatients with pharyngeal cancer
      were compared with 37,168 and 11,076 outpatient controls without cancer. Among
      hospitalized persons, the prevalence of GERD was higher among patients with
      laryngeal cancer (8.9 vs 4.0%, p < 0.0001) and pharyngeal cancer (6.2 vs 3.8%, p
      < 0.0001). In a multivariable logistic regression analysis that was controlled
      for age, gender, ethnicity, smoking, and alcohol, GERD was associated with an
      adjusted odds ratio (OR) of 2.40 for laryngeal cancer among hospitalized patients
      (95% CI 2.15-2.69, p < 0.0001) and an adjusted OR of 2.38 (95% CI 1.87-3.02, p <
      0.0001) for pharyngeal cancer. For outpatients, GERD was associated with an
      adjusted OR = 2.31 (95% CI 2.10-2.53) for laryngeal cancer and adjusted OR = 1.92
      (95% CI 1.72-2.15). CONCLUSIONS: Among US veterans, the risk for laryngeal or
      pharyngeal cancers is modestly increased in the presence of GERD. This effect
      seems to be independent of age, gender, smoking, and alcohol intake.

PMID- 11467627
TI  - Relationship between straining, transient lower esophageal sphincter relaxation,
      and gastroesophageal reflux in children.
AB  - OBJECTIVE: Physical straining such as deep inspiration or coughing may induce
      gastroesophageal reflux (GER) by overcoming feeble lower esophageal sphincter
      (LES) pressure. The role of straining as a provocant of GER has not been analyzed
      systematically in children. It was our aim to examine the contribution of
      straining to the occurrence of GER with particular attention to its relationship
      to transient LES relaxations, which are a major mechanism of the occurrence of
      GER in pediatric patients. METHODS: Concurrent esophageal manometry and pH
      monitoring was performed for 4 h postprandially in six children with esophagitis
      (age 9 months to 12 yr). Analysis was performed on isolated single strain
      episodes, defined as an increased intragastric pressure > 10 mm Hg. When a drop
      of esophageal pH < 4.0 was noted within 15 sec after any part of a strain, this
      strain was defined as related to the reflux episode. RESULTS: The median value of
      basal LES pressure was 10 mm Hg (range 1-18). In all, 134 analyzable strains and
      87 analyzable reflux episodes were recorded. Isolated strains were associated
      with 20 reflux episodes (23%). Reflux was observed more frequently with strains
      that occurred during transient LES relaxations (12/40) than straining when the
      LES was contracted (8/94) (p < 0.01). Sustained strain (35%) and inspiratory
      strain (25%) were the major patterns of straining related to reflux. CONCLUSION:
      Straining provoked reflux infrequently and simultaneous occurrence of straining
      and transient LES relaxation was important in determining the occurrence of
      strain-related reflux in pediatric patients with reflux esophagitis.

PMID- 11467628
TI  - Relationship between esophageal dysfunction and neuropathy in diabetic patients.
AB  - OBJECTIVE: Few studies have compared esophageal dysfunction with diabetic
      neuropathy, and their relationship is not yet clear. The aim of this study was to
      investigate the relationship between esophageal function and diabetic neuropathy.
      METHODS: A total of 59 patients with type 2 diabetes were studied. Long-term
      ambulatory esophageal pH and motility monitoring were performed. The motor nerve
      conduction velocity (MCV) and coefficient of variation of R-R intervals (CVRR)
      were also examined. RESULTS: The 59 patients were classified into four groups:
      group 1 consisted of patients with both diabetic autonomic neuropathy (DAN) and
      diabetic motor neuropathy (DMN), group 2 had DMN alone, group 3 had DAN alone,
      and group 4 had neither DAN nor DMN. In pH monitoring, differences were observed
      among the four groups in DeMeester score, total number of acid reflux episodes,
      and % time pH < 4 (p < 0.05). A correlation was observed between % time pH < 4
      and MCV; however, no correlation with CVRR was observed. In motility monitoring,
      differences were observed among the four groups in amplitude of peristaltic waves
      (p < 0.001), rising velocity of peristaltic waves (p < 0.01), and percentage of
      effective peristalsis (p < 0.01). A correlation was observed between esophageal
      motility and MCV; however, no correlation with CVRR was observed. CONCLUSIONS:
      Esophageal motility disorder and abnormal acid reflux were related to DMN in
      diabetic patients. A significant correlation was found between esophageal
      dysfunction and MCV. However, no significant correlation was found between
      esophageal dysfunction and CVRR.

PMID- 11467629
TI  - The role of acid and duodenal gastroesophageal reflux in symptomatic GERD.
AB  - OBJECTIVE: Mixed reflux of acid and duodenal contents frequently occurs in
      patients with gastroesophageal reflux disease (GERD). The aim of this study was
      to establish the contribution of acid and duodenal gastroesophageal reflux (DGER)
      to symptoms in patients with presumed GERD. METHODS: A total of 72 patients (37
      women), mean age 45 yr (+/-2 yr), underwent 24-h ambulatory pH and Bilitec
      monitoring. Patients pressed a marker button when experiencing typical symptoms.
      For each symptom episode, minimal pH and maximal bilirubin optical density in a 2
      or 4-min interval were calculated. For each patient, the symptom index (SI) and
      symptom-association probability for acid and for bile reflux were determined.
      RESULTS: A total of 544 symptom episodes were identified. Using a 2-min interval,
      28% were associated with acid reflux, 9% with DGER, and 12% with mixed reflux. No
      significant difference was found when a 4-min interval was used. A positive SI
      for acid reflux was present in 21% of the patients and for DGER in 14%. All
      patients with a positive SI for DGER had also a positive SI for acid reflux. A
      positive symptom-association probability for acid reflux was present in 22% of
      the patients, for DGER in 7% of the patients, and for mixed reflux in 10% of the
      patients. CONCLUSIONS: Symptom episodes in patients with presumed GERD are more
      related to acid reflux than to DGER. DGER does not play a major role in producing
      typical esophageal symptoms.

PMID- 11467630
TI  - Effects of low doses of erythromycin on the 13C Spirulina platensis gastric
      emptying breath test and electrogastrogram: a controlled study in healthy
      volunteers.
AB  - OBJECTIVE: Electrogastrography and stable isotope gastric emptying breath tests
      (GEBTs) are relatively simple, noninvasive tests of gastric motor function that
      may be useful in monitoring the effects of therapeutic interventions. It was our
      primary objective to examine the effects of low dose i.v. erythromycin on the
      results of the 13C Spirulina platensis GEBT and electrogastrography. We were also
      interested in evaluating the reproducibility of these tests. METHODS: In 10
      healthy subjects (five female, ages 23-37 yr), we simultaneously performed the
      GEBT, using a prepackaged meal (340 kcal), and electrogastrography on each of
      four different occasions separated by at least 1 wk. After performance of
      baseline studies, they were repeated in random order after the infusion of 50 mg
      of erythromycin (Er50), 100 mg erythromycin (Er100), and a placebo (saline).
      Breath samples were obtained at baseline and at 75, 90, and 180 min after the
      meal and T1/2 and Tlag calculated. Electrogastrography recordings began 30 min
      before the test meal and continued for 2 h after the meal. RESULTS: Baseline and
      placebo T1/2 and Tlag were similar. Er50 resulted in a modest acceleration of
      gastric emptying (T1/2 Er50 vs baseline vs placebo = 104.0 vs 132.7 vs 125.5 min)
      and reduction in lag time (Tlag Er50 vs baseline vs placebo = 47.2 vs 61.5 vs
      56.2 min). A similar decrease was seen in response to Er100. The baseline and
      placebo fasting and fed electrogastrography parameters were similar. After
      infusion of Er100, the percentage of normal slow waves in the first postprandial
      hour decreased relative to baseline and placebo (percent normogastria Er100 vs
      baseline vs placebo = 64.1+/-7.5 vs 82.4+/-6.4 vs 79.7+/-5.5). This corresponded
      with an increase in percent tachygastria during the same period and an overall
      decrease in the mean dominant frequency. Similar but less striking changes were
      seen after administration of Er50. Replicate GEBTs showed a high degree of
      reproducibility both within and between individuals for T1/2 and Tlag. In
      contrast, replicate electrogastrograms revealed moderate to high variability for
      all parameters except the dominant frequency. CONCLUSION: The stable isotope GEBT
      utilizing 13C S. platensis demonstrates responsiveness to the prokinetic effects
      of low dose i.v. erythromycin and good reproducibility.

PMID- 11467631
TI  - Outcomes of initial noninvasive Helicobacter pylori testing in U.S. primary care
      patients with uninvestigated dyspepsia.
AB  - OBJECTIVE: Recent European trials demonstrate that testing and treatment for
      Helicobacter pylori (H. pylori) is an effective alternative to prompt endoscopy
      in uninvestigated dyspepsia. The eventual endoscopy rate after H. pylori testing,
      which is a key determinant of cost-effectiveness, is unknown in the United
      States. Our aim was to determine the endoscopy rate after H. pylori testing in
      primary care practice in the United States and to compare outcomes among
      seropositive and seronegative patients. METHODS: We performed a retrospective
      review with mean 13 month follow-up of primary care patients with dyspeptic
      symptoms tested with office-based H. pylori serology. RESULTS: Of 268 adults
      tested (37+/-11 yr, 58% women), 57 (21%) were seropositive and 49/57 (86%)
      received eradication therapy. Endoscopy or contrast radiography was performed on
      19% of seropositive and 19% of seronegative patients (p = 0.97). Annualized
      median disease-related expenditures were similar among seropositive and
      seronegative patients ($228 [$93-$654] vs $366 [$107-$1268], p = 0.19). However,
      aggregate expenditures were substantially lower than the cost of endoscopy alone
      ($816 [$296-$970]). On follow-up, seropositive and seronegative patients had
      similar numbers of primary care visits (2.9+/-3.2 vs 3.5+/-3.6, p = 0.23),
      prolonged antisecretory medication use (25 vs 33%, p = 0.27), and specialist
      referrals (23 vs 24%, p = 0.83). CONCLUSION: In a United States center, 81% of
      primary care patients tested for H. pylori did not undergo endoscopy, and
      patients incurred significantly lower median expenditures after noninvasive H.
      pylori testing than the cost of endoscopy alone. Seropositive and seronegative
      patients experienced comparable outcomes after H. pylori testing.

PMID- 11467632
TI  - Effects on 24-hour intragastric pH: a comparison of lansoprazole administered
      nasogastrically in apple juice and pantoprazole administered intravenously.
AB  - OBJECTIVE: To compare the 24-h intragastric pH effects of lansoprazole, 30 mg
      administered nasogastrically, with pantoprazole, 40 mg administered i.v. METHODS:
      Healthy adults were enrolled in an open label, two-way crossover, single-center
      study. Thirty milligrams of lansoprazole (administered nasogastrically in apple
      juice) or pantoprazole (i.v.) were administered once daily at 8:00 AM for 5
      consecutive days with at least a 2-wk washout period between the regimens.
      Ambulatory 24-h intragastric pH was monitored at baseline and on days 1 and 5 of
      each treatment period. Blood specimens were collected on days I and 5 for
      pharmacokinetic parameter determinations. RESULTS: Thirty-three adults completed
      both crossover periods, with the exception of one patient with a zero
      lansoprazole plasma concentration on day 1 of period 2. Lansoprazole, 30 mg per
      nasogastric tube, produced significantly higher mean 24-h intragastric pH values
      relative to pantoprazole, 40 mg i.v., on both day 1 (3.05 vs 2.76, p < 0.002) and
      day 5 (3.65 vs 3.45, p = 0.024). Lansoprazole sustained the intragastric pH above
      3 (days 1 and 5), 4, and 5 (day 1) significantly longer relative to pantoprazole.
      Lansoprazole's time to the maximum observed concentration and area under the
      plasma concentration-time curve over the 24-h time interval increased
      significantly from day I to day 5 (1.7 h vs 2.0 h and 1865 ng x h/ml vs 2091 ng x
      h/ml, respectively), and a significant increase in half-life relative to day 1
      (0.96 h) was observed on day 5 (1.03 h) during pantoprazole treatment.
      CONCLUSION: Lansoprazole, 30 mg administered nasogastrically, effectively
      controls intragastric pH and is an alternative to i.v. pantoprazole in patients
      who are unable to swallow solid dosage formulations.

PMID- 11467633
TI  - Influence of gender on proximal gastric motor and sensory function.
AB  - OBJECTIVE: Gender-related differences have been demonstrated with regard to GI
      motility: gallbladder contraction, colonic transit, and gastric emptying are
      delayed in women. It is not known whether gender influences proximal gastric
      motility and perception. METHODS: We have studied the influence of gender on
      proximal gastric motility and perception under fasting and postprandial
      conditions by retrospective analysis of data obtained in 99 healthy volunteers
      (42 men, 57 women) who participated in barostat studies performed according to
      standardized protocols at the Leiden University Medical Center (Leiden, The
      Netherlands) between 1996 and 2000. RESULTS: Minimal distending pressure (MDP)
      was significantly higher in women than in men (respectively, 6.8+/-0.2 vs 5.5+/
      0.2 mm Hg; p < 0.001). During stepwise pressure distensions pressure-volume
      curves were similar in both sexes after correction for MDP, whereas perception of
      fullness and abdominal pressure increased significantly (p < 0.05) more rapidly
      in women. Before the meal intragastric volumes (at MDP + 2 mm Hg) did not differ
      between sexes. After the meal gastric relaxation in the first 30 min did not
      differ in women and men (respectively, 186+/-23 ml and 140+/-32 ml). However,
      from 30 until 90 min after the meal a significantly (p < 0.05) delayed return of
      intragastric volume to basal was seen in women. Perception of postprandial nausea
      was significantly (p < 0.01) increased in women. Perception of postprandial
      fullness remained increased for a longer period of time in women. CONCLUSIONS:
      Proximal gastric motility and perception are influenced by gender. Gender-related
      differences in postprandial proximal gastric motility and perception should be
      taken into account in barostat studies comparing patients with controls.

PMID- 11467634
TI  - The decision-making value of magnetic resonance cholangiopancreatography in
      patients seen in a referral center for suspected biliary and pancreatic disease.
AB  - OBJECTIVE: To assess the ability of MRCP to alter the differential diagnosis and
      to prevent diagnostic and/or therapeutic ERCP. The diagnostic accuracy of
      magnetic resonance cholangiopancreatography (MRCP) for biliary and pancreatic
      disease is well documented. Some believe MRCP may prevent diagnostic ERCP or add
      useful information, however there are no reports of its impact on clinical
      management. METHODS: Consecutive patients referred for ERCP underwent clinic
      evaluation, then MRCP, and then ERCP. In Phase 1, the number of differential
      diagnoses and the perceived need for diagnostic ERCP were evaluated after each
      step by the endoscopist who performed the ERCP. In Phase 2, the process was
      repeated after presenting clinical information and MRCP results to different
      individual physicians: another endoscopist, a hepatologist, a radiologist, and a
      surgeon (all were blinded to ERCP results). RESULTS: Forty patients were
      enrolled. Clinical contexts were jaundice (19.7%), abnormal liver enzymes
      (42.6%), abdominal pain (11.5%), recurrent acute pancreatitis (11.5%), and
      suspected complications of chronic pancreatitis (14.7%). In Phase 1, adding MRCP
      information to diagnostic ERCP information did not change the mean number of
      differential diagnoses significantly and prevented no therapeutic ERCP. In Phase
      2, adding MRCP to clinical information only (without ERCP) reduced the
      differential diagnosis significantly for the radiologist and the surgeon only and
      would have prevented < or =3% of diagnostic and therapeutic ERCP for all
      physicians. CONCLUSION: The value of MRCP information may be limited if patient
      selection is inappropriate and may differ in physicians depending on their
      speciality.

PMID- 11467635
TI  - Hemoconcentration: an early marker of severe and/or necrotizing pancreatitis? A
      critical appraisal.
AB  - OBJECTIVE: A study was designed to reevaluate hemoconcentration as an early
      marker of severe and/or necrotizing pancreatitis and compare it against contrast
      enhanced CT, the gold standard to diagnose acute necrotizing pancreatitis.
      METHODS: This prospective study covers the years 1988-1999 for 316 patients (202
      male, 114 female) with a first attack of acute pancreatitis. The role of the
      hematocrit as an early marker of severe and/or necrotizing pancreatitis has been
      retrospectively evaluated against the prospectively obtained data. They all
      underwent a CT within 72 h after admission. In addition to the CT-controlled
      diagnosis of interstitial/necrotizing pancreatitis, the following variables were
      used to assess severity: initial organ failure according to the Atlanta
      classification; indication for artificial ventilation and/or dialysis; Ranson
      score adjusted for etiology; Imrie score; Balthazar score; length of stay in
      intensive care unit (ICU); total hospital stay; development of pancreatic
      pseudocysts; indication for operation (necrosectomy); and mortality.
      Hemoconcentration on admission was defined as a hematocrit level >43.0% for male
      and >39.6% for female patients. Logistic regression was used to assess the
      correlation between hemoconcentration and the severity of variables. RESULTS:
      Hematocrit, as a single parameter measured on admission, had the same sensitivity
      and negative predictive value as the more complicated Ranson and Imrie scores
      obtained only after 48 h. However, its specificity, positive predictive value,
      and total accuracy were lower. Hemoconcentration significantly correlated with
      the Balthazar score (differential diagnosis between interstitial and necrotizing
      pancreatitis), stay in ICU, and total hospital stay. Sensitivity and specificity
      of the hematocrit cut-off level of 43.0% for male and 39.6% for female patients
      to detect necrotizing pancreatitis were 74% and 45%, respectively. The positive
      predictive value was 24% and the negative predictive value 88%. Receiver
      operation characteristics (ROC) curve values for several cut-offs did not result
      in more ideal levels. CONCLUSION: Hemoconcentration does not significantly
      correlate with important clinical outcome variables of acute pancreatitis
      including organ failure and mortality rate. Its prognostic value is comparable to
      the more complicated Ranson and Imrie scores obtained only after 48 h. The major
      value of this single easily obtainable and cheap parameter on admission lies in
      its high negative predictive value. In the absence of hemoconcentration, contrast
      enhanced CT may be unnecessary on admission unless the patient does not improve.

PMID- 11467636
TI  - How gastroenterologists inform patients of results after lower endoscopy.
AB  - OBJECTIVE: Little is known about how gastroenterologists communicate endoscopic
      findings and biopsy results to their patients. We sought to determine the factors
      that may influence this behavior. METHODS: A survey questionnaire was developed
      and mailed to the 80 members of the Delaware Valley Society for GI Endoscopy.
      Information was obtained on the demographic characteristics and responses to six
      case vignettes prepared to examine communication patterns. We determined possible
      influences of conscious sedation and the benignity or severity of findings on
      communication practices. RESULTS: Sixty-one surveys (76%) were completed and
      analyzed. Endoscopists immediately inform patients of normal results. For
      abnormal results, 92% would immediately inform nonsedated patients versus 79%
      that would inform sedated patients (p < 0.008). Analysis of responses to the case
      vignettes indicated that 82% of endoscopists would immediately reassure the
      patient about a benign appearing (< 1 cm) polyp, but only 70% would do so for a
      polyp > 2 cm (p < 0.01). In contrast, when presented with a frank malignancy, 94%
      would inform the patient. Eighty-four percent of endoscopists would telephone
      results of a benign pathology report, but only 34% would telephone report a
      dysplastic lesion (p < 0.001). There was no correlation between the response rate
      and various demographic parameters such as physician age, type of, or length of
      time in practice. CONCLUSIONS: Gastroenterologists usually report normal findings
      immediately, but are less likely to do so after use of sedation or encountering
      abnormal findings. Most of those surveyed would use the telephone to communicate
      abnormal findings.

PMID- 11467637
TI  - Photodynamic therapy for palliation of nonresectable bile duct cancer-
      preliminary results with a new diode laser system.
AB  - OBJECTIVES: Preliminary results of photodynamic therapy (PDT) of bile duct cancer
      have shown astonishingly good results in the reduction of cholestasis,
      improvement of quality of life, and even prolongation of the survival time.
      Unfortunately, the existing dye laser systems are large and costly, and their
      maintenance is expensive. Therefore, we investigated the feasibility of a diode
      laser system for PDT of nonresectable bile duct cancer. METHODS: Eight patients
      with nonresectable bile duct cancer were treated. Forty-eight hours after i. v.
      application of 2 mg/kg body weight of Photosan-3, light activation was performed
      by a transpapillary (four patients) or percutaneus (four patients) access. We
      used a cylindrical diffusor tip and illuminated using a wavelength of 633+/-3 nm
      and a total energy of 200 J/cm2. All patients were additionally provided with
      bile duct endoprostheses after PDT. RESULTS: Four weeks after initial PDT all
      patients showed a marked reduction of bile duct stenosis. The median serum
      bilirubin value declined from 5.8 mg/dl (2.0-10.1) to 1.0 mg/dl (0.8-4.4). The
      median survival time at the time of writing is 119 days (52-443). Five patients
      are still alive. In four patients we could change from percutaneous to
      transpapillary drainage after PDT, two patients showed infectious complications.
      CONCLUSION: PDT with the diode laser system seems to be effective in reducing
      malignant bile duct stenosis. This treatment is minimally invasive and has a low
      specific complication rate. Randomized, controlled studies comparing PDT with the
      insertion of endoprostheses and long term follow-up of results are needed to
      confirm the promising short term results.

PMID- 11467638
TI  - A randomized, double blind study of interleukin 10 for the prevention of ERCP
      induced pancreatitis.
AB  - OBJECTIVES: Inflammatory cytokines are released during acute pancreatitis.
      Interleukin 10 (IL-10) is a potent antiinflammatory cytokine with
      immunosuppressive and antiinflammatory activities. IL-10 has been shown to
      attenuate pancreatitis in an animal model. A double blind, placebo-controlled
      pilot study was conducted to evaluate the safety and efficacy of low dose IL-10
      for the prevention of ERCP-induced pancreatitis. METHODS: Patients were
      randomized to receive a single i.v. dose of recombinant human IL-10 (8 microg/kg)
      or a placebo i.v. bolus injection 15 min before the procedure. Pancreatitis was
      defined as abdominal pain radiating to the back associated with elevated amylase
      or lipase two or more times the upper limit of normal requiring hospitalization
      for > or =2 days. Severity of pancreatitis was based on days of hospitalization.
      RESULTS: Two hundred patients were enrolled (101 IL-10, 99 placebo). No
      difference in age, gender, degree of pancreatic duct filling, therapeutic
      intervention, or complication was detected between the two groups. Eleven
      patients in the IL-10 group and nine patients in the placebo group had
      pancreatitis (p = 0.65). The median length of hospitalization was 4 days in the
      IL-10 group and 3 days in the placebo group (p = 0.75). CONCLUSIONS: IL-10 at the
      8-microg/kg i.v. dose was not effective in reducing the incidence or severity of
      ERCP-induced pancreatitis. Further investigations are necessary to determine if
      manipulation of the cytokine pathway can prevent ERCP-induced pancreatitis.

PMID- 11467639
TI  - Is push enteroscopy useful in patients with malabsorption of unclear origin?
AB  - OBJECTIVE: The aim of this study was to determine the diagnostic value of push
      enteroscopy in patients with chronic diarrhea and malabsorption of unclear
      origin. METHODS: From January, 1997, to September, 1999, 16 consecutive patients
      with chronic diarrhea and biological signs of intestinal malabsorption but no
      evidence of celiac disease were explored by push enteroscopy. Previous duodenal
      histological findings had been normal in seven patients and abnormal but
      inconclusive in nine patients. Endoscopic and histological findings in the
      duodenum and in the jejunum were compared. RESULTS: Push enteroscopy with jejunal
      biopsy yielded a diagnosis in comparison with duodenal biopsy in two of 16 (12%)
      patients, respectively, in two of the nine (22%) patients with abnormal but
      inconclusive findings on duodenal biopsy, and none of the seven patients with
      normal duodenal histology. In the two patients in whom jejunal biopsy had
      diagnostic value but duodenal biopsy did not, the final diagnoses were invasive
      intestinal lymphoma and microsporidiosis. CONCLUSION: Push enteroscopy had
      diagnostic value in only 12% of patients with malabsorption of unclear origin,
      all of whom had had abnormal but inconclusive duodenal histological findings.
      Push enteroscopy with jejunal biopsy appears to have limited diagnostic value in
      patients with chronic diarrhea and malabsorption, especially when duodenal
      biopsies are histologically normal.

PMID- 11467640
TI  - The comorbid occurrence of other diagnoses in patients with ulcerative colitis
      and Crohn's disease.
AB  - OBJECTIVES: The comorbidity between inflammatory bowel disease (IBD) and other
      diagnoses may help to shed light on the etiology and pathophysiology of IBD. The
      US Vital Statistics offer the opportunity to study causes of death broken down by
      comorbid disease associations. The aim of this study was to analyze the presence
      of comorbid conditions in persons who died from ulcerative colitis or Crohn's
      disease. METHODS: The numbers of deaths from ulcerative colitis and Crohn's
      disease were retrieved from the computerized 1991-1996 data files of the National
      Center for Health Statistics. Comorbid associations between other diagnosis and
      ulcerative colitis or Crohn's disease were expressed as age-, gender-, and race
      standardized proportional mortality ratios. RESULTS: Ulcerative colitis and
      Crohn's disease showed, in general, similar patterns of comorbidity. Both
      diseases were associated with similar sets of GI complications, such as
      intestinal obstruction and stasis, mucosal inflammation and infection, vascular
      complications, and complications related to fistula and abscess formation.
      Extraintestinal complications of both IBD involved disorders of the hepatobiliary
      system, urinary system, and various coagulopathies. Ulcerative colitis alone was
      found to be associated with Hirschsprung's disease and schizophrenia, whereas
      Crohn's disease alone was found to be related with osteoporosis and amyloidosis.
      CONCLUSIONS: No completely unexplained or hitherto undescribed association was
      revealed. The numerous intestinal and extraintestinal complications associated
      with IBD serve as a reminder of the systemic nature and the resultant clinical
      severity of both ulcerative colitis and Crohn's disease.

PMID- 11467641
TI  - Impact of cessation of smoking on the course of ulcerative colitis.
AB  - OBJECTIVES: The incidence and severity of ulcerative colitis (UC) are higher in
      nonsmokers than in smokers. The natural course of UC in smokers who stop smoking
      is not known. The aim of this study was to determine the impact of cessation of
      smoking on the course of UC among the cohort of patients regularly seen at our
      institution. METHODS: The severity of UC, as judged by the occurrence of flare
      ups and the need for systemic steroids, immunosuppressive drugs and colectomy,
      was determined in 32 patients with UC who stopped smoking after the diagnosis of
      UC. We compared the period after cessation of smoking (7-yr mean follow-up) with
      the period between the onset of the disease and the cessation of smoking (9-yr
      mean duration). The course of UC in this group was compared with that of 32
      nonsmokers and 32 continuing smokers matched for sex, age, and age at onset.
      RESULTS: In patients who quit, cessation of smoking was followed by an increase
      in the rate of years with active disease (p < 0.01), years with hospitalization
      (p < 0.05) and years with major medical therapy (oral steroids, intravenous
      steroids, and azathioprine, p < 0.01). After cessation of smoking, the rate of
      years with immunosuppressive therapy was significantly greater in ex-smokers and
      nonsmokers than in continuing smokers (p < 0.01). The risk of colectomy in ex
      smokers after smoking cessation was similar to that of nonsmokers and continuing
      smokers. CONCLUSIONS: In smokers with UC who stop smoking, the severity of the
      disease increases after smoking cessation, with an increase in the disease
      activity and the need for hospital admission and major medical therapy. In
      addition, the need for azathioprine therapy becomes similar to that of
      nonsmokers.

PMID- 11467642
TI  - The relationship between inflammatory bowel disease and socioeconomic variables.
AB  - OBJECTIVES: Inflammatory bowel diseases (IBD) are chronic diseases associated
      with considerable morbidity. This morbidity may have an impact on the ability of
      patients to remain employed, on their marital status, and on their ability to
      complete a course of higher education. It has long been held that IBD patients
      are of a higher socioeconomic status and more educated than the general
      population. Our aim was to determine the relationship between IBD and employment,
      income, disability, education, and marital status in two population-based data
      sets based in the province of Manitoba, Canada. METHODS: Two studies are reported
      here. In study A, we surveyed persons with IBD, using the population-based
      University of Manitoba IBD Database, created in 1995-1996. We compared these IBD
      patients to the general population with respect to employment, education, and
      marital status using data from the 1996 National Population Health Survey. IBD
      patients were queried as to their socioeconomic status as of the time of
      diagnosis and also at the time of the survey (1995-1996). In study B, we used a
      database that linked health care and census variables to determine differences in
      employment, income, occupation, and marital status among individuals who met the
      administrative definition of IBD (created in forming the University of Manitoba
      IBD Database, based on ICD-9-CM codes 555 for Crohn's disease and 556 for
      ulcerative colitis) compared with the rest of working-age population. RESULTS: In
      study A we found that, compared with the general population, patients with IBD
      were more likely to be unemployed. Crohn's disease appeared to affect employment
      more than ulcerative colitis. IBD patients, however, had a low rate of reporting
      themselves as disabled (1.3%). Among those married when diagnosed with IBD,
      approximately 10% of men and up to 20% of women were no longer married 5 yr
      later. More patients with IBD were married in 1995 compared with the general
      population; however, more were also divorced. Fewer patients with IBD achieved
      postsecondary education. In study B, we found that individuals with IBD were
      twice as likely to be out of the labor force as were controls. Sedentary
      occupations were twice as likely to be associated with IBD. The income, education
      level, and marital status of IBD patients were not significantly different from
      those of controls. CONCLUSIONS: Individuals with IBD at some time in the course
      of their illness are more likely not to be working than are those in the general
      population. Based on employment status and job classification, as well as income
      and education, IBD patients are not of a higher socioeconomic status as
      previously reported. IBD patients are at least as likely as the general
      population to be married.

PMID- 11467643
TI  - Disappointing sensitivity of endoscopic markers for villous atrophy in a high
      risk population: implications for celiac disease diagnosis during routine
      endoscopy.
AB  - OBJECTIVE: Endoscopic markers of duodenal villous atrophy (VA) can facilitate
      diagnosis of celiac disease during routine upper GI endoscopy. We studied their
      sensitivity for VA in a large series of patients undergoing GI endoscopy
      specifically for duodenal biopsy. Poor sensitivity in this setting would have
      significant and adverse implications for their performance during routine
      endoscopy. METHODS: All patients with VA on duodenal biopsy performed for
      positive serum endomysial antibody (EmA) and/or clinical features suggestive of
      celiac disease were included. The second part of duodenum was inspected carefully
      for endoscopic markers using videogastroscopes. RESULTS: Of 129 patients studied,
      99 (77%) had at least one endoscopic markers. The most commonly seen marker were
      a mosaic pattern mucosa (68 patients, 53%) and scalloping of duodenal folds (74
      patients, 57%). The prevalence of markers was significantly lower for partial VA
      (15 of 26 patients, 58%) than for subtotal or total VA (84 of 103 patients, 82%)
      (p < 0.02). CONCLUSIONS: Endoscopic markers have disappointing sensitivity even
      in a population at high risk of celiac disease, particularly for partial VA.
      Their performance may be even poorer in an unselected dyspeptic population.
      Although they may help improve diagnosis rates among patients with nonspecific
      dyspeptic symptoms, many patients, particularly those with milder enteropathy,
      will be missed. As celiac disease is an important cause of dyspepsia,
      consideration should be given to serological screening to further improve
      diagnosis rates, as few centers will have the resources to routinely biopsy all
      patients.

PMID- 11467644
TI  - Increase in cyclooxygenase-2 and nitric oxide-synthase-2 mRNAs in pouchitis
      without modification of inducible isoenzyme heme-oxygenase-1.
AB  - OBJECTIVES: The pathophysiology of pouchitis occurring after ileal pouch-anal
      anastomosis remains controversial. Prostaglandins and nitric oxide synthesized in
      excess by cyclooxygenase-2 and nitric oxide synthase-2 are thought to be involved
      in the inflammatory process. Because heme oxygenase-1, by its antioxidant
      properties, could modulate inflammatory reaction, we analyzed mRNAs of the three
      enzymes (cyclooxygenase-2, nitric oxide synthase-2, and heme oxygenase-1) in
      patients with ileal pouch-anal anastomosis. METHODS: Endoscopic biopsies were
      obtained in eight patients with normal ileal pouch-anal anastomosis, in eight
      patients with pouchitis, and in normal ileum of six healthy subjects. A relative
      quantitative RT-PCR was performed to determine the levels of cyclooxygenase-2,
      nitric oxide synthase-2, and heme oxygenase-1 mRNAs. RESULTS: Cyclooxygenase-2
      and nitric oxide synthase-2 mRNAs were increased both in normal ileal pouch-anal
      anastomosis and in pouchitis, compared with healthy subjects. Pouchitis disease
      activity index was correlated with mRNA levels of cyclooxygenase-2 (r = 0.71; p <
      0.01) and nitric oxide synthase-2 (r = 0.51; p < 0.05). Heme oxygenase-1 mRNA
      levels were not significantly different in patients versus healthy subjects.
      CONCLUSIONS: The increase in cyclooxygenase-2 and nitric oxide synthase-2 mRNA
      levels both in pouchitis and normal ileal pouch-anal anastomosis demonstrates
      that a latent inflammatory process occurs in the ileal pouch mucosa. This
      inflammatory process was not found to be associated with an induction of heme
      oxygenase mRNA, a possible regulator of the inflammatory response.

PMID- 11467645
TI  - Outcome of cytomegalovirus infections in patients with inflammatory bowel
      disease.
AB  - OBJECTIVE: The aim of this study was to determine the outcome of cytomegalovirus
      (CMV) infections complicating the course of inflammatory bowel disease (IBD).
      METHODS: The records and clinical courses were reviewed for all IBD patients who
      were evaluated at the IBD Center of the Cedars-Sinai Medical Center and who
      developed CMV infection. RESULTS: Ten patients with severe, medically refractory
      IBD (five ulcerative colitis, three Crohn's colitis, and two indeterminate
      colitis) developed CMV infection. All but two were hospitalized with exacerbation
      of their underlying disease and were receiving immunosuppressive treatment with
      steroids, thiopurines, and/or cyclosporine at the time CMV infection was
      recognized. Eight patients had documented colonic CMV (one had concurrent upper
      GI tract involvement), one developed interstitial CMV and Pneumocystis carinii
      pneumonia, and one developed primary CMV mononucleosis. Prompt treatment with
      ganciclovir and withdrawal of immunosuppressive treatment resulted in gradual
      improvement and induction of remission of the underlying IBD in five patients.
      The patient with concomitant CMV and P. carinii pneumonitis died. In two
      patients, treatment with ganciclovir did not alter the clinical course of their
      IBD, and one of them underwent colectomy. In one patient CMV was found on the
      resected colonic specimen. One patient with primary CMV infection responded also
      to ganciclovir treatment. CONCLUSIONS: CMV infection may aggravate the course of
      seemingly refractory IBD in patients who either fail to respond or experience
      worsening of symptoms despite immunosuppressive therapy. Expedient evaluation,
      prompt treatment intervention with ganciclovir, and withdrawal of
      immunosuppressive treatment may avoid complications and mortality. This regimen
      leads to improvement of the underlying IBD in most patients.

PMID- 11467646
TI  - Hyperhomocysteinemia and inflammatory bowel disease: prevalence and predictors in
      a cross-sectional study.
AB  - OBJECTIVE: Homocysteine is a sulfur-containing amino acid formed during the
      demethylation of methionine. Vitamin B12 and folate deficiency and therapy with
      antifolate drugs may predispose patients with inflammatory bowel disease (IBD) to
      hyperhomocysteinemia. The known associations between hyperhomocysteinemia and
      smoking, osteoporosis, and thrombosis make it an interesting candidate as a
      pathogenetic link in IBD. The aim of this study was to identify the prevalence
      and risk factors of hyperhomocysteinemia in patients with IBD. METHODS: Sixty
      five consecutive IBD patients were recruited from a tertiary outpatient
      gastroenterology practice. Fasting plasma homocysteine levels were measured,
      along with vitamin B12 and folate. Data regarding medication use, multivitamin
      use, disease location and severity, and extraintestinal manifestations of IBD
      were gathered. Homocysteine levels in 138 healthy control subjects were compared
      with the IBD cohort, and adjustments for age and sex were made using logistic
      regression. Multivariate analysis was performed to seek predictors of
      homocysteine levels. RESULTS: The mean age in the IBD cohort was 42+/-13.4 yr (+/
      SD), and 43% were male. The mean disease duration was 13.8+/-9.4 yr, and 32% had
      used steroids within the last 3 months. Immunomodulator therapy had been used in
      32%, and 75% had had an intestinal resection. Osteoporosis was present in 33% of
      patients. Five patients had experienced venous thrombosis or stroke, but only one
      of these had hyperhomocysteinemia. Of the 10 IBD patients (15.4%) with
      hyperhomocysteinemia, only two had vitamin B12 deficiency. The homocysteine
      levels in the IBD cohort cases and controls were 8.7 and 6.6 micromol/L,
      respectively (p < 0.05). IBD significantly increased the risk of
      hyperhomocysteinemia (adjusted odds ratio = 5.9 [95% CI: 1.5-24]). Advanced age,
      male sex, vitamin B12 deficiency or lower vitamin B12 serum levels, and
      multivitamin therapy were independently associated with higher homocysteine
      levels in the multivariate analysis (R2 = 0.55; p = 0.001). CONCLUSIONS:
      Hyperhomocysteinemia is significantly more common in patients with IBD compared
      with healthy controls, and is associated with lower (but not necessarily
      deficient) vitamin B12 levels.

PMID- 11467647
TI  - Visceral afferent hypersensitivity in irritable bowel syndrome--evaluation by
      cerebral evoked potential after rectal stimulation.
AB  - OBJECTIVES: Gut hypersensitivity has been shown to be present in irritable bowel
      syndrome. The current study sought to determine the involvement or
      hypersensitivity of the gut afferents, objectively, by recording cerebral evoked
      potential after rectal stimulation. METHODS: In 13 patients with irritable bowel
      syndrome and nine healthy controls, rectal perception thresholds to electrical
      stimulation were measured, and cerebral evoked potentials were recorded from 2 cm
      behind vertex (Cz') after rectal stimulation electrically (frequency 1 Hz,
      duration 0.5 ms) at an intensity 50% above perception threshold and with filter
      setting 1-250 Hz. RESULTS: Perception thresholds to rectal electrical stimuli in
      patients with irritable bowel syndrome were lower than controls (p < 0.05).
      Rectal stimulation led to recognizable and reproducible cerebral evoked
      potentials. P1, N1, P2 latencies in patients with irritable bowel syndrome were
      shorter than that in controls (p < 0.05). P1/N1 amplitude was greater in patients
      with irritable bowel syndrome than in controls (p < 0.05). CONCLUSIONS: The
      shorter latency and increased amplitude of cerebral evoked potential after rectal
      stimulation in patients with irritable bowel syndrome compared to controls
      provide objective evidence supporting visceral afferent hypersensitivity as the
      underlying mechanism in irritable bowel syndrome.

PMID- 11467648
TI  - Rectal compliance, capacity, and rectoanal sensation in fecal incontinence.
AB  - OBJECTIVE: Assessments of the pathophysiology of fecal incontinence are skewed
      toward anal sphincter function; however, rectal compliance, rectoanal sensation
      and capacity may also be relevant. The aim of this study was to evaluate the
      usual and some novel diagnostic approaches in fecal incontinence. METHODS: In 22
      unselected patients with fecal incontinence (21 F, 33-75 yr), we quantified: 1)
      symptoms, anorectal manometry, and anal ultrasound; 2) anal perception of
      temperature and light touch; 3) rectal sensitivity and compliance to distension;
      and 4) rectal reservoir function. Control values were obtained from two groups of
      11 (seven F, 32-53 yr), and 32 (18 F, 19-44 yr) volunteers. RESULTS: Patients had
      urge (14), passive (four), or combined (four) fecal incontinence; symptoms were
      mild in three, moderate in nine, and severe in 10 patients. Most had low
      sphincteric pressures and ultrasonic abnormalities. Temperature perception was
      impaired (p < 0.05) in incontinent patients, to a greater extent in the proximal
      anal canal and in patients with passive, as opposed to urge, incontinence.
      Intraluminal pressures for sensations of rectal distension were lower in
      incontinent patients (p = 0.02). Artificial stools elicited sensations of rectal
      filling at lower volumes than did a barostat bag, and in patients with urge, as
      opposed to passive, incontinence. In patients and controls, the sensation of
      urgency was associated (r2 = 0.2, p < 0.01) with rectal compliance. CONCLUSIONS:
      We confirm that temperature sensation is impaired, and perception of rectal
      distension is not always reduced in fecal incontinence. Artificial stool tended
      to induce sensations at lower volumes than did balloon inflation. Altered sensory
      mechanisms may contribute to the pathophysiology of fecal incontinence.

PMID- 11467649
TI  - Pediatric Crohn's disease: risk factors for postoperative recurrence.
AB  - OBJECTIVE: Postoperative recurrence of Crohn's disease in adults has been
      extensively studied; however, the course of Crohn's disease after surgery in
      children has not been well defined. The aim of this study was to examine the
      postoperative course of pediatric Crohn's disease and the factors that may
      predict early postoperative recurrence. METHODS: We identified 100 resective
      surgeries in 79 children with Crohn's disease seen at the Children's Hospital of
      Philadelphia between 1978 and 1996. A retrospective, multivariable analysis of
      factors potentially influencing postoperative clinical recurrence was performed.
      Preoperative and postoperative height measurements were compared, and z scores
      were computed for height-for-age. Two-tailed t test was used for the analysis.
      RESULTS: Clinical recurrence rates were 17% at 1 yr, 38% at 3 yr, and 60% at 5
      yr. Patients with colonic Crohn's disease had a significantly shorter
      postoperative recurrence-free interval (median 1.2 yr) than patients with
      ileocecal (median 4.4 yr) or diffuse disease (median 3.0 yr) (p = 0.01). On
      multivariable analysis, a high Pediatric Crohn's Disease Activity Index at the
      time of surgery (p = 0.01) and preoperative use of 6-mercaptopurine (6-MP) (p <
      0.005) were also independently associated with higher postoperative recurrence
      rates. There was a significant improvement in z scores for height (p = 0.04)
      after surgery. CONCLUSIONS: In children undergoing resective surgery for Crohn's
      disease, high rates of postoperative Crohn's disease recurrence are associated
      with severe disease at the time of surgery, colonic Crohn's disease, and the
      preoperative use of 6-MP. Patients who require preoperative use of 6-MP are
      likely to suffer from a more aggressive disease and would benefit from
      postoperative 6-MP prophylaxis. Height growth was improved after intestinal
      resection for Crohn's disease.

PMID- 11467650
TI  - B2 microglobulin: is it a reliable marker of activity in inflammatory bowel
      disease?
AB  - OBJECTIVES: The aims of this study were to investigate a possible positive
      correlation between B2-microglobulin (B2-M) serum levels and the severity and
      activity of inflammatory bowel disease (IBD); and to examine whether B2-M levels
      reflect IBD extent. METHODS: We examined B2-M serum levels in 87 ulcerative
      colitis (UC) patients, 74 with Crohn's disease (CD) and 68 control subjects,
      using an enzymatic method. The reliability of the measuring method was assessed
      by evaluating serum B2-M in 18 patients suffering from chronic renal failure
      (CRF). The severity and activity of IBD was estimated using the van Hees Activity
      Index and the True-love-Witts criteria for CD and UC patients respectively.
      Endoscopic evaluation for UC patients was done according to Baron's et al.
      classification; Riley's et al. criteria were used for histological evaluation.
      RESULTS: B2-M serum levels were significantly increased in all CD patients except
      those in remission. After 6 months treatment a second blood sample taken from CD
      patients with initially elevated B2-M levels proved to be compatible with CD
      severity at that time. Such a positive correlation was not assessed in UC
      patients; therefore, a second blood sample was considered unnecessary.
      Furthermore, CD patients with pancolitis, ileal-caecal, or small intestinal
      disease had higher B2-M levels than those with left-sided, anal, or perianal
      disease. CONCLUSIONS: B2-M serum levels could prove to be a useful marker in
      assessing not only the activity, severity, and extent of CD but the treatment
      efficacy as well.

PMID- 11467651
TI  - Gender-related differences in IBS symptoms.
AB  - OBJECTIVE: Women are more likely than men to report irritable bowel syndrome
      (IBS) symptoms as well as chronic visceral and musculoskeletal pain. The study
      tests the general hypothesis that female IBS patients differ from their male
      counterparts in symptoms related to the viscera and musculoskeletal system, and
      that these differences are related to the menstrual cycle. METHODS: Seven hundred
      fourteen Rome positive IBS patients were evaluated for GI and extracolonic
      symptoms, psychological symptoms (SCL-90R), and quality of life (QOL) (SF-36). In
      addition, 54 postmenopausal women were compared with 61 premenopausal women and
      54 age-matched males, all with IBS. RESULTS: Male and female subjects reported
      similar GI levels of symptom severity and psychological problems. Abdominal
      distension associated with a sensation of bloating was more commonly reported by
      female patients, as were symptoms of constipation. Female patients more often
      reported nausea, alterations of taste and smell, and unpleasant sensations on the
      tongue, muscle stiffness in the morning, greater food sensitivity, and side
      effects from medications. Forty percent of female patients reported menstrual
      cycle-related worsening of symptoms, but few symptom differences were found
      between pre- and postmenopausal women, making it unlikely that most of the gender
      differences observed are directly tied to the menstrual cycle. CONCLUSIONS:
      Female patients report higher levels of a variety of intestinal and nonintestinal
      sensory symptoms despite similar levels of IBS severity, abdominal pain,
      psychological symptoms, and illness impact. The apparent differences in
      sensitivity to nonpainful visceral sensations, medications, and food may
      represent altered sensory processes, autonomic responses, and/or cognitive
      hypervigilance.

PMID- 11467652
TI  - Assessment of hepatitis B virus DNA and hepatitis C virus RNA in the common
      bedbug (Cimex lectularius L.) and kissing bug (Rodnius prolixus).
AB  - OBJECTIVE: Historical clinical studies suggest the potential for insect-borne
      transmission of human hepatitis viruses. Studies of hepatitis B virus (HBV)
      persistence in insects were performed before the advent of molecular techniques,
      and studies to assess possible insect-borne transmission of hepatitis viruses
      have not yet been performed. The aim of this study was to determine, using
      molecular techniques, whether HBV and hepatitis C virus (HCV) persist in and are
      excreted in the feces of the bedbug Cimex lectularius L. and kissing bug Rodnius
      prolixus after an infectious meal. METHODS: Blood-feeding insects from the insect
      order Hemiptera (Cimex lectularius L. and Rhodnius prolixus) were fed on blood
      from infected patients with high titers of HBV, HCV, and control uninfected
      patients. Insects and insect excrement were collected at weekly intervals and
      tested for HBV DNA and HCV RNA using the polymerase chain reaction. RESULTS: HBV
      DNA was detected in bedbugs and excrement up to 6 wk after feeding on an
      infectious meal. HBV DNA was also detected in most kissing bugs and excrement up
      to 2 wk after feeding. HCV RNA was not detected in bedbugs at any time after
      feeding. CONCLUSIONS: We did not detect HCV RNA in bedbugs after feeding on an
      infectious meal. Our data provide molecular evidence to suggest that HBV may
      persist in Hemiptera. Additional studies are ongoing to determine whether this
      viral persistence is capable of infection.

PMID- 11467653
TI  - Health-related quality of life in chronic liver disease: the impact of type and
      severity of disease.
AB  - OBJECTIVE: The type and severity of chronic liver disease may have different
      effects on health-related quality of life (HRQL). The aim of our study was to
      determine whether HRQL in patients with chronic liver disease differs by type and
      severity of disease and to identify which clinical and physiological factors
      affect this impairment. METHODS: In this study, HRQL was measured with a generic
      (Short Form 36) and a liver disease-specific (Chronic Liver Disease
      Questionnaire) questionnaire. Clinical, demographic, and laboratory data were
      collected at office visits. Patient's HRQL scores were compared with the
      published norms and to the chronically ill populations. A total of 353 patients
      (mean age 50 yr, 51% men) with chronic liver disease, either viral disease
      (hepatitis B and C), cholestatic disease (primary biliary cirrhosis or primary
      sclerosing cholangitis), or hepatocellular disease were enrolled in the study.
      RESULTS: In general, HRQL in patients with chronic liver disease was lower than
      the normal population and was similar to that of patients with chronic
      obstructive pulmonary disease or congestive heart failure. In cirrhotic patients,
      some dimensions of HRQL were less impaired in patients with cholestatic disease
      than in those with hepatocellular diseases. More severe disease (higher Child's
      class) was associated with a lower Chronic Liver Disease Questionnaire score and
      the Short Form 36's physical component summary scores. Older age had a weak
      negative association with the physical aspects of HRQL. CONCLUSIONS: We conclude
      that chronic liver disease substantially reduces HRQL, and this impact does not
      differ markedly by type of disease. Older age and measures of disease severity
      were associated with poorer HRQL.

PMID- 11467654
TI  - Risk factors for the development of renal dysfunction in hospitalized patients
      with cirrhosis.
AB  - OBJECTIVE: Hospitalized patients with liver cirrhosis are predisposed to acute
      renal failure. We sought to identify the role of liver disease severity,
      infectious complications, and in-hospital treatment with aminoglycosides as risk
      factors for acute renal failure among patients with cirrhosis. METHODS: In a
      retrospective, case-control study at the Albuquerque VA Medical Center,
      electronic and manual chart review was employed to identify all hospitalized
      patients with a diagnosis of cirrhosis and normal renal function (serum
      creatinine < or = 1.3 mg/dl) at the time of hospitalization. Cases were defined
      as patients who developed renal dysfunction (increase in creatinine of > or = 1.0
      mg/dl) within 15 days of hospitalization, and the remaining patients were
      controls. RESULTS: Of 93 patients, there were 23 cases and 70 controls. There
      were no significant differences in age, etiology of cirrhosis, serum levels of
      albumin, or bilirubin, prothrombin time, encephalopathy, bacteremia, urinary
      tract infection, or occurrence of esophageal variceal bleeding. Patients who
      developed renal dysfunction were more likely to have ascites (87% vs 41%, p <
      0.01), spontaneous bacterial peritonitis (44% vs 1%, p < 0.01), and treatment
      with i.v. aminoglycosides (48% vs 19%, p < 0.01). In a multivariate logistic
      regression analysis, aminoglycosides treatment was a strong risk factor for renal
      dysfunction (adjusted odds ratio = 4.0, 95% CI = 1.4-11), independent of the
      severity of liver disease or peritonitis. CONCLUSION: Avoidance of aminoglycoside
      antibiotics may reduce the occurrence of renal dysfunction in hospitalized
      patients with cirrhosis. In addition, close monitoring of renal function should
      be employed among patients with ascites and/or spontaneous bacterial peritonitis.

PMID- 11467655
TI  - Overexpression of interferon gamma-inducible protein 10 in the liver of patients
      with type I autoimmune hepatitis identified by suppression subtractive
      hybridization.
AB  - OBJECTIVE: To clarify gene expression profiles in the liver may elucidate the
      pathogenesis of type I autoimmune hepatitis (AIH). Using suppression subtractive
      hybridization (SSH), we identified genes overexpressed in the liver of AIH.
      METHODS: A small liver biopsy sample from a patient with definite AIH was
      available to be analyzed in our system. By mixing cDNA synthesized from this
      sample as a 'tester' and cDNA from a normal liver as a 'driver,' we subtracted
      cDNA to enrich genes overexpressed in AIH. After polymerase chain reaction (PCR)
      amplification and subcloning, we identified subtracted genes by sequencing 50
      randomly selected clones. RESULTS: Only one cDNA fragment, which is identical to
      interferon inducible protein 10 (IP-10), was overexpressed by > 10 times in the
      liver of AIH, as compared with control. We confirmed IP-10 overexpression in all
      eight patients with AIH by reverse transcription PCR. Immunohistochemical
      analysis demonstrated increased IP-10 expression in hepatocytes in the liver of
      AIH. Reverse transcription PCR analysis of 63 liver biopsy samples with various
      liver diseases revealed that IP-10 expression was significantly higher in AIH (p
      = 0.025) and chronic hepatitis C (p = 0.0043) than in other liver diseases.
      Interestingly, the amount of IP-10 mRNA expression was correlated with serum ALT
      values in AIH (p = 0.0006), but not in chronic hepatitis C (p = 0.43).
      CONCLUSION: These results indicate the IP-10 expression in the liver might be
      used as a preferential marker of AIH, and that IP-10 has some pathophysiological
      roles in the liver damage of AIH.

PMID- 11467656
TI  - Effects of different octreotide dosages on splanchnic hemodynamics and glucagon
      in patients with TIPS.
AB  - OBJECTIVE: The aim of this study was to evaluate the hemodynamic effects of
      octreotide in patients treated with transjugular intrahepatic portosystemic stent
      shunt in relation to plasma levels of octreotide and glucagon and the correlation
      between portal pressure and noninvasive Doppler parameters. METHODS: In 15
      fasting patients, we i.v. administered isotonic sodium chloride followed by
      octreotide 25 microg/h and 100 microg/h, each over 1 h. We measured portal
      pressure (PP) directly and portal vein blood flow velocity by Doppler ultrasound
      simultaneously and calculated portal vascular resistance (PVR) and portal venous
      flow (PVF). Blood samples were taken for glucagon and octreotide (mean +/- SE).
      RESULTS: Octreotide reduced PP (120': -7.7+/-2.2%, p < 0.01 vs baseline; 180': -
      11.4+/-2.1%, p < 0.01 vs baseline) and PVF (120': -21.7+/-31.7%, p < 0.01 vs
      baseline; 180': -11.6+/-18.1%, p < 0.05 vs baseline). Glucagon decreased with the
      increase in octreotide levels and showed a correlation with the decrease in PP
      and with PVF. In patients with a high PVR, we found a close inverse correlation
      between PP and portal vein blood flow velocity (r = -0.83, p = 0.03) as well as
      Cl (r = 0.81, p = 0.05), whereas poor correlation was found in patients with low
      PVR. CONCLUSIONS: Octreotide caused a dose-related, moderate but sustained
      reduction in PP in patients with transjugular intrahepatic portosystemic stent
      shunt. PVR seems to be an important parameter that influences the efficacy of
      octreotide and the relation between PP and noninvasive Doppler parameters.

PMID- 11467657
TI  - A new percutaneous approach for the treatment of hydatid cysts of the liver.
AB  - OBJECTIVES: The aims of this study were to investigate the efficacy of a new
      percutaneous treatment modality of hydatid disease of the liver and to present
      the results of long term follow-up. METHODS: Eighty-seven patients (55 female,
      mean age 43.5 yr) with 98 hydatid cysts (73 type I, 15 type II, and 10 type III)
      in the liver underwent percutaneous treatment. All patients were examined by
      ultrasonography and some of them were examined by CT. They were all positive by
      indirect hemagglutination test. Sonographic guidance was used in all patients.
      The procedure included the puncture and free drainage of the cyst fluid. After
      free drainage was stopped, absolute alcohol and polidocanol 1% were used as
      sclerosing agents. The patients were followed-up with periodic ultrasonographic
      examinations. RESULTS: The mean follow-up time was 33 months. The mean diameter
      of the cysts decreased from 77.0+/-2.7 mm to 63.0+/-2.5 mm (p < 0.001). The
      entire cyst cavity filled with a solid echo pattern in 32 cysts, two-thirds of
      the cyst cavity showed a pseudotumor echo pattern in 34 cysts, and one-third of
      the cyst cavity showed a pseudotumor pattern in 23 cysts, whereas no pseudotumor
      appearence was observed in eight cysts. Apart from an anaphylactoid reaction
      observed in one patient, no major complication occurred during the follow-up
      period. CONCLUSIONS: Long term results indicate that this new percutaneous
      treatment modality of the hydatid disease of the liver is an effective and safe
      method without causing major complications. Percutaneous treatment of hydatid
      cysts of the liver offers good results and should be the first choice, especially
      for patients who are contraindicated to surgery.

PMID- 11467658
TI  - Comorbid occurrence of liver and pancreas disease in United States military
      veterans.
AB  - OBJECTIVE: The clinical epidemiology of the comorbidity between liver and
      pancreas disease is unknown. The Patient Treatment File of the Department of
      Veterans Affairs contains the computerized records of all inpatients treated in
      172 Department of Veterans Affairs hospitals distributed throughout the United
      States. This large database offers a unique opportunity to study the epidemiology
      of liver-pancreas comorbidity (LPC). METHODS: In a case-control study, 6,393 LPC
      cases were compared to 34,513 controls with alcoholic liver disease and liver
      cirrhosis alone and 68,038 controls without liver or pancreas disease.
      Multivariate logistic regression analysis was used to assess the joint influence
      of multiple risk factors on the occurrence of LPC. RESULTS: LPC occurred in 15.6%
      of patients with alcoholic liver disease and liver cirrhosis identified in the
      Patient Treatment File between 1990 and 1993. Compared to controls with liver
      disease alone, LPC cases were characterized by younger age (odds ratio = 0.88 per
      age decade, CI = 0.86-0.90) and African American (2.33, 2.18-2.48) or Hispanic
      (1.24, 1.12-1.38) ethnicity. Compared to controls with neither liver nor pancreas
      disease, LPC cases were characterized by male gender (1.67, 1.28-2.17), African
      American (1.41, 1.32-1.50) or Hispanic (2.04, 1.82-2.30) ethnicity, more frequent
      history of alcoholism (29.5, 26.7-32.6), and being divorced (1.35, 1.26-1.44).
      CONCLUSIONS: Comorbidity of liver and pancreas disease is relatively common in
      the veteran population. Such patients are more frequently divorced and of African
      American or Hispanic ethnicity, and present with a history of excessive
      alcoholism at a relatively young age.

PMID- 11467659
TI  - Does high body fatness increase the risk of presence and growth of colorectal
      adenomas followed up in situ for 3 years?
AB  - OBJECTIVE: Obesity is an increasing problem for industrialized nations. The
      incidence of colorectal cancer has also risen during the last decades. However,
      information is scarce about the association between the colorectal cancer
      precursors, adenomatous polyps, and body composition. Our aim was to find out if
      body fatness is related to the presence of polyps and of growth of adenomas of <
      or =9 mm observed in situ over 3 yr. METHODS: Twenty-eight outpatients with
      colorectal polyps and 50-75 yr of age were compared with 34 sex- and age-matched
      (+/-5 yr) polyp-free healthy controls. The polyp patients were randomly selected
      from a double blind 3-yr placebo-controlled endoscopic follow-up and intervention
      study against growth and recurrence of polyps among 116 polyp-bearing
      outpatients. Triceps skinfold thickness (TSF) was measured by a Harpenden caliper
      and total body fat percentage (BF%) by Futrex 5000. Dietary intake was calculated
      in a 5-day dietary record by weighing. Demograpic data, including smoking and
      alcohol habits, were registered by an interview and self-administrated
      questionnaires. Weight and height were measured. RESULTS: TSF and BF% ranked 66%
      of the individuals into the same quartiles, and 34% were ranked into the adjacent
      quartiles. The coefficient of correlation between TSF and BF% was highly
      significant (r = 0.90, p < 0.01, n = 62). TSF, BF%, and body mass index (kg/m2)
      did not differ between polyp patients and controls in either crude or adjusted
      analyses. Adenoma growth was, however, highly associated with increasing levels
      of TSF (p = 0.004), BF% (p = 0.02), and body mass index (p = 0.006). CONCLUSIONS:
      Our data suggest that high body fatness is a promoter of adenoma growth. Similar
      results were obtained with the caliper and Futrex 5000, which lends credibility
      to this study. For repeated documentation, a larger study population should be
      investigated. To our knowledge, this is the first case-control study to
      investigate the relationship between body composition and growth of adenoma by
      follow-up in situ over 3 yr.

PMID- 11467660
TI  - Anatomy plate.

PMID- 11467661
TI  - Symptomatic gastrointestinal amyloidosis in an HIV-infected patient.
AB  - We report a rare case of symptomatic GI amyloidosis in an HIV-infected patient
      who ultimately developed uncontrollable upper GI bleeding. Gastric and jejunal
      biopsies revealed amyloidosis. Although the patient's history suggested the
      possibility of secondary amyloidosis, immunohistochemical staining together with
      serum electrophoresis and immunofixation revealed the presence of lambda light
      chains indicating primary amyloidosis.

PMID- 11467662
TI  - Celiac disease in a patient with a congenital deficiency of intestinal
      enteropeptidase.
AB  - We report on a 40-yr-old man with both primary enteropeptidase deficiency and
      celiac disease. He suffered from severe intestinal malabsorption and growth
      failure as a child. Enteropeptidase deficiency was found and pancreatic enzyme
      replacement therapy resulted in a growth spurt. Enteropeptidase levels in his
      intestinal mucosa and intraluminal fluid remained very low throughout childhood
      and early adult life. Celiac disease was confirmed by characteristic
      abnormalities in tests of intestinal function and in mucosal biopsies, which
      recovered when he instituted a gluten-free diet. He remains clinically intolerant
      to gluten as an adult. Enteropeptidase levels have remained abnormally low
      whether or not his intestinal mucosa has been normal in response to gluten
      restriction. Enteropeptidase levels have previously been shown to be normal in
      untreated celiac patients. The relationship between the two disorders remains
      unclear.

PMID- 11467663
TI  - Nocardia asteroides lung abscess in acute ulcerative colitis treated with
      cyclosporine.
AB  - Cyclosporine is a potent suppresser of cell-mediated immunity that is mainly used
      in organ transplantation to prevent rejection. It is also being used increasingly
      outside of transplantation and probably is the only new treatment to have made an
      impact in acute ulcerative colitis (UC) resistant to steroid therapy. We describe
      a case of Nocardia asteroides lung abscess in a patient treated with cyclosporine
      for acute steroid resistant UC that was successfully managed with antibiotics and
      by discontinuing cyclosporine. With increasing use of cyclosporine for acute UC
      it is to be anticipated that opportunistic infections such as Nocardia will be
      more frequently encountered in the future.

PMID- 11467664
TI  - Cholestatic jaundice associated with the use of metformin.
AB  - We report a patient who developed cholestatic jaundice shortly after initiation
      of treatment with metformin hydrochloride. Ultrasound of the liver and abdominal
      CT were normal. An ERCP showed normal biliary anatomy. A percutaneous liver
      biopsy was obtained showing marked cholestasis, with portal edema, ductular
      proliferation, and acute inflammation. Metformin hydrochloride was discontinued,
      and the patient's jaundice resolved slowly over a period of several months. Given
      the onset of his jaundice 2 wk after the initiation of metformin, we believe that
      this case represents an example of metformin-associated hepatotoxicity, the first
      such case reported.

PMID- 11467665
TI  - Antibody testing for ulcerative colitis--more letters?

PMID- 11467666
TI  - If at first you don't succeed...Try again?

PMID- 11467667
TI  - Anal warts and anal cancer.

PMID- 11467668
TI  - Fecal bacteriotherapy or probiotics for the treatment of intestinal diseases?

PMID- 11467669
TI  - Herpes simplex virus esophagitis in an immunocompetent host with sepsis.

PMID- 11467670
TI  - Hormones and offspring sex ratios associated with celiac disease.

PMID- 11467671
TI  - Scarce information about the risk of cancer in colorectal hyperplastic polpys and
      polyposis.

PMID- 11467672
TI  - Riluzole-induced acute pancreatitis.

PMID- 11467673
TI  - Wilson disease in two consecutive generations: an exceptional family.

PMID- 11467674
TI  - Acute pancreatitis induced by isoniazid in the treatment of tuberculosis.

PMID- 11467675
TI  - Serum transaminase values in HIV-infected patients with previous HBV infection,
      with and without HCV antibodies.

PMID- 11467676
TI  - Successful treatment of megacolon associated with colitis with a nitric oxide
      synthase inhibitor.

PMID- 11467677
TI  - Infliximab treatment and pregnancy outcome in active Crohn's disease.

PMID- 11467678
TI  - Effects of propyonil-l-carnitine topical irrigation in distal ulcerative colitis:
      a preliminary report.

PMID- 11467679
TI  - Defecation syncope associated with splanchnic sympathetic dysfunction and cured
      by permanent pacemaker insertion.

PMID- 11467680
TI  - Hepatitis E-associated subacute liver failure: a rare indication for liver
      transplantation.

PMID- 11467681
TI  - Helicobacter pylori and severe morning sickness.

PMID- 11467682
TI  - Systemic lupus erythematosus presenting with acute fatal pancreatitis as an
      initial manifestation.

PMID- 11467683
TI  - Small intestinal bacterial overgrowth and symptoms of irritable bowel syndrome.

PMID- 11467684
TI  - Pruritus can be soothing in acute viral hepatitis.

PMID- 11467685
TI  - Sulindac-associated choledocholithiasis.

PMID- 11467686
TI  - Conception soon after discontinuing interferon/ribavirin therapy: a successful
      outcome.

PMID- 11467687
TI  - No evidence for mutagenic effects of ribavirin: report of two normal pregnancies.

PMID- 11467688
TI  - Cyclic vomiting syndrome triggered by nonsedated upper GI endoscopy.

PMID- 11467689
TI  - Hereditary non-polyposis colorectal cancer syndrome: combined risk of
      gastrointestinal and gynaecological cancer.

PMID- 11467690
TI  - Obstetric practice and faecal incontinence three months after delivery.
AB  - OBJECTIVE: To determine whether obstetric and maternal factors relate to faecal
      incontinence at three months postpartum. SETTING: Maternity units in Aberdeen
      (Scotland), Birmingham (England) and Dunedin (New Zealand). POPULATION: All women
      who delivered during one year in the three maternity units. METHODS: Postal
      questionnaire at three months postpartum, to obtain information on faecal
      incontinence, linked to obstetric casenote data. MAIN OUTCOME MEASURES:
      Prevalence of faecal incontinence. RESULTS: 7879 questionnaires were returned, a
      71.7% response rate. The prevalence of faecal incontinence was 9.6%, with 4.2%
      reporting this more often than rarely. Logistic regression, confined to
      primiparae, showed that forceps delivery was a predictor of an increased risk of
      symptoms (OR = 1.94, 95% CI 1.30 to 2.89) while vacuum extraction was not
      associated. Caesarean section was marginally associated with a reduced risk (OR =
      0.58, 95% CI 0.35 to 0.97). Older maternal age, Indian sub-continent ethnic
      origin and body mass index 'not known' also showed significant associations. No
      associations were found for induced labour, duration of second stage labour,
      episiotomy, laceration or birthweight. CONCLUSIONS: Women delivered by forceps
      had almost twice the risk of developing faecal incontinence, whereas vacuum
      extraction was not associated with faecal incontinence at three months
      postpartum. Caesarean section appears to offer some protection.

PMID- 11467691
TI  - Does a second delivery increase the risk of anal incontinence?
AB  - OBJECTIVE: To evaluate the prevalence of anal incontinence and anal sphincter
      defects after a first vaginal delivery and assess the effect of a second
      delivery. DESIGN: Prospective cohort study using postal questionnaires assessing
      incontinence to flatus and stools at three and thirty months postnatally and anal
      endosonography at three months following delivery. SETTING: Recruitment was from
      the antenatal clinic at the University Hospitals of Geneva, Switzerland.
      POPULATION: One hundred women with a vaginal delivery of their first child. MAIN
      OUTCOME MEASURES: Prevalence of anal incontinence and anal sphincter defects.
      RESULTS: Anal incontinence was reported by 16/92 (17%) of women at three months
      after delivery and by 11/77 (14%) at 30 months. At that time, 5/54 (9%) with no
      further delivery reported incontinence, compared with 6/ 23 (26%) of those who
      had had another delivery (RR 2.8, 95% CI 1.0-8.3). Anal sphincter defects were
      diagnosed by endosonography in 46/87 (53%) women and were associated with
      reported incontinence at both three months (RR 1.9; 95% CI 1.4-2.6) and 30 months
      (RR 1.9: 95% CI 1.3-2.8) after delivery. The prevalence of anal incontinence at
      30 months was highest (5/13, 39%) among those in whom a sphincter defect was
      diagnosed by endosonography after their first delivery and with a second
      delivery. CONCLUSION: Anal incontinence after childbirth is associated with
      defects of the anal sphincter diagnosed by endosonography. Subsequent deliveries
      increase the risk of incontinence, particularly among women with a sphincter
      defect diagnosed after the first delivery.

PMID- 11467692
TI  - Maternal height and newborn size relative to risk of intrapartum caesarean
      delivery and perinatal distress.
AB  - OBJECTIVE: To estimate the changes, in risk of intrapartum caesalrean delivery
      and perinatal distress that may be introduced through increased birth size,
      resulting from interventions such as improving nutrition of the mother; and to
      characterise delivery risk relative to maternal stature by birth size. DESIGN:
      Model these risks using data from the Guatemalan Perinatal Study. SETTING: The
      antenatal clinic of the Gynaecology and Obstetrics Hospital of the Guatemalan
      Social Security Institute in Guatemala City serving predominantly working class
      women. POPULATION: Women who had their first prenatal visit between April 1984
      and January 1986. METHODS: Multivariate logistic regression models were developed
      to estimate incidence of intrapartum caesarean delivery and perinatal distress
      and used to calculate changes in risk associated with changes in size. MAIN
      OUTCOME MEASURES: Incidences of intrapartum caesarean delivery and perinatal
      distress. RESULTS: A woman of 146cm height (-1 SD) relative to another of 160 cm
      (+1 SD) has a 2.5 times higher risk of intrapartum caesarean delivery. An
      increase in newborn head circumference and weight (from -1 SD to +1 SD) are each
      independently associated with an increase in risk of intrapartum caesarean
      delivery (2.0 times and 1.5 times. respectively). An increase in birthweight from
      2,450 g to 2,550 g is associated with a decrease in risk of perinatal distress of
      34/1,000 cases and an increase in risk of intrapartum caesarean delivery of
      8/1,000 cases. CONCLUSIONS: Increases in fetal growth comparable to those
      attributable to improved nutrition during pregnancy are associated with a larger
      decrease in risk of perinatal distress relative to the increase in risk of
      intrapartum caesarean delivery for the mother. Greater maternal stature is
      associated with lower risk of intrapartum caesarean delivery.

PMID- 11467693
TI  - Changes in the vaginal flora after two percent clindamycin vaginal cream in women
      at high risk of spontaneous preterm birth.
AB  - OBJECTIVE: To analyse alterationS in the vaginal flora after 2% clindamycin
      vaginal cream or placebo administered for the prevention of preterm delivery in
      high risk women. DESIGN: Observational study during a randomised multicentre
      double-blind placebo controlled trial. SETTING: Twelve city hospitals in The
      Netherlands. PARTICIPANTS: One hundred and sixty-eight women were enrolled.
      Alterations in the vaginal flora could be analysed in one hundred and twenty-four
      women by comparing the Nugent score on entry to the trial and at 31 weeks'
      gestation. The Nugent score was classified into normal, intermediate and
      bacterial vaginosis. INTERVENTIONS: Two percent clindamycin vaginal cream or
      placebo cream administered daily for seven days at week 26 of pregnancy. MAIN
      OUTCOME: Changes in the vaginal flora at week 31 of pregnancy. RESULTS: The
      placebo group consisted of 64 women and the clindamycin group of 60 women. At
      week 31 the vaginal flora was similar to week 26 with placebo cream but changed
      from normal vaginal flora to intermediate or bacterial vaginosis with 2%
      clindamycin vaginal cream. CONCLUSION: Obstetricians should not prescribe 2%
      clindamycin vaginal cream to pregnant women with normal vaginal flora in order to
      reduce the incidence of preterm birth. because it has no beneficial effects and
      is actually harmful. 2% Clindamycin vaginal cream encourages the presence of
      bacterial vaginosis which is epidemiologically associated with preterm birth.

PMID- 11467694
TI  - Growth hormone binding protein in normal and aneuploid pregnancy: a paradoxical
      decrease in trisomy 18.
AB  - OBJECTIVE: To explore whether abnormalities in growth hormone binding protein
      (GHBP) may underlie the growth restriction associated with fetal aneuploidy.
      DESIGN: A retrospective casecontrol study. SETTING: Monash Medical Centre.
      Clayton, Victoria, Australia. POPULATION: Twenty-one trisomy 18, and 30 trisomy
      21 pregnancies, and 170 chromosomally normal pregnancies at 15-18 weeks of
      gestation representing three to five controls per case matched for source,
      gestation and duration of storage. METHODS: GHBP was measured using a ligand
      immunofunctional assay RESULTS: In the chromosomally normal pregnancies GHBP
      levels decreased slightly but significantly across the narrow gestational window
      studied. Compared with controls, levels of GHBP, expressed as median (95% CI)
      multiples of the median (MoM). in the trisomy 21 pregnancies were similar, 1.0
      (0.92-1.39) MoM and 1.27 (1.04-1.50) MoM, respectively; P = 0.061 (Mann-Whitney U
      test) but were significantly reduced in the trisomy 18 pregnancies, 0.68 (0.5 1
      0.84) MoM: P = 0.0014 (Mann-Whitney U test). CONCLUSIONS: These data suggest that
      decreased levels of maternal growth hormone binding protein, and by implication
      growth hormone receptor complement, may underlie the early severe growth
      restriction that is characteristic of trisomy 18.

PMID- 11467695
TI  - Human chorionic gonadotrophin inhibition of pregnant human myometrial
      contractility.
AB  - OBJECTIVE: To evaluate the effect of human chorionic gonadotrophin (hCG) on
      pregnant human myometrial contractility in vitro and to determine whether the hCG
      elicited effect was oestrogen dependant. METHODS: Isometric tension recording was
      performed under physiological conditions in isolated myometrial strips from
      biopsies obtained at elective caesarean section. The effect of cumulative
      additions of hCG (0.001, 0.01, 0.1, 1.0 and 10 iu/mL) on myometrial contractility
      was evaluated. Secondarily, the contractile activity of pregnant myometrium
      following hCG exposure was investigated in tissue pre-treated with beta
      oestradiol. RESULTS: hCG exerted a statistically significant relaxant effect on
      pregnant human myometrial tissue. The relaxant effect increased with increasing
      concentrations of hCG from 8.96% (SEM 2.06) (0.001 iu/mL hCG: P < 0.01 ) to a net
      cumulative total of 58.50% (SEM 3.74) (10 iu/mL hCG; P < 0.01). The relaxant
      effect was also time-dependant, increasing in magnitude throughout the duration
      of experiments. Beta-oestradiol did not significantly affect the response of
      myometrial tissue to hCG. CONCLUSIONS: These results clearly demonstrate that hCG
      exerts a significant concentration-dependant relaxant effect on human myometrial
      tissue obtained rate in pregnancy. These findings outline an inhibitory
      physiological role of hCG on human myometrial contractility and raise the
      possibility of its potential use as a tocolytic.

PMID- 11467696
TI  - Plasma P-selectin is elevated in the first trimester in women who subsequently
      develop pre-eclampsia.
AB  - OBJECTIVE: To report plasma concentrations of the adhesion cell molecule P
      selectin during pregnancy to determine the effect of subsequent development of
      hypertension and pre-eclampsia. DESIGN: A longitudinal study. METHODS: A
      longitudinal study involving 70 women followed up from early pregnancy; 20 who
      subsequently developed pre-eclampsia were compared with 24 who developed
      gestational hypertension and 26 normotensive women with normal obstetric outcome.
      The determination of citrate plasma soluble P-selectin levels throughout
      pregnancy was performed using a commercial quantitative sandwich immunoassay kit.
      The temporal course of plasma P-selectin in the three groups of subjects was
      analysed. RESULTS: There was no significant difference in mean plasma P-selectin
      concentration between normotensive and gestational hypertensive subjects at any
      stage of pregnancy. Using a cutoff level of 60 ng/mL, P-selectin concentration at
      10-14 weeks had a negative predictive value for pre-eclampsia of almost 99%. Mean
      plasma P-selectin concentrations were significantly elevated by 10-14 weeks in
      women who later developed pre-eclampsia (P < 0.001). CONCLUSIONS: Our data
      support an inflammatory model for pre-eclampsia whereby endothelial cell
      activation may be secondary to a primary inflammatory response. Plasma P-selectin
      has significant potential as a first trimester clinical marker of pre-eclampsia.

PMID- 11467697
TI  - Prevalence and features of pancreatic islet cell autoimmunity in women with
      gestational diabetes from different ethnic groups.
AB  - OBJECTIVE: To assess the prevalence and characteristics of islet cell
      autoimmunity amongst women with gestational diabetes selected from South Asian
      and Afro-Caribbean as well as European populations. DESIGN: Cross-sectional
      retrospective survey of subject cohort. POPULATION: Three hundred and twenty-one
      women with a recent history of gestational diabetes (173 European, 86 South Asian
      and 62 Afro-Caribbean), a median (range) of 22 (1-150) months postpartum.
      RESULTS: Antibodies to Glutamic acid decarboxylase were found in 13 (4%) of these
      women. There was no difference in the prevalence of anti-glutamic acid
      decarboxylase positivity between the three ethnic groups (European 4.6%, South
      Asian 3.5%, Afro-Caribbean 3.2%). Anti-glutamic acid decarboxylase positive women
      were leaner than anti-glutamic acid decarboxylase negative women (body mass
      index, median (upper-lower quartile) 23.9 (22.5-26.7) vs 26.6 (23.4-30.5)kg/m2, P
      = 0.03, P = 0.049 allowing for ethnicity). There was no difference between
      glutamic acid decarboxylase-positive and glutamic acid decarboxylase-negative
      women for age, family history of diabetes, waist/hip ratio, prevalence of insulin
      treatment during pregnancy, postpartum glucose status, lipid profile and indices
      of insulin action and beta-cell function. CONCLUSIONS: Markers of islet cell
      autoimmunity are found as frequently in gestational diabetes women of South Asian
      and Afro-Caribbean origin, as they are in European subjects. Identification of
      future risk of type 1 diabetes is relevant to the planning of clinical management
      and intervention strategies in women with gestational diabetes of all major
      ethnic groups.

PMID- 11467698
TI  - Does the increased risk of preterm delivery in teenagers persist in pregnancies
      after the teenage period?
AB  - OBJECTIVE: To study the associations between low maternal age at first birth and
      the risks of very and moderately preterm birth, in first birth and in second
      successive birth in adulthood. DESIGN: Population-based cohort study. SETTING:
      Sweden. POPULATION Women aged less than 25 years at first birth (n = 275,933),
      having two successive live single births from 1973 through 1993. METHODS: Odds
      ratios with 95 percent confidence intervals were calculated to estimate the
      effect of low maternal age at first birth. Analyses of first births were adjusted
      for year of first birth and maternal education and in second births also for
      previous pregnancy outcomes and interpregnancy interval. MAIN OUTCOME MEASURES:
      Very preterm birth (less than 33 completed weeks) and moderately preterm birth
      (33-36 completed weeks). RESULTS: Compared with women aged 20 to 24 years at
      first birth, mothers aged 13 to 15 years were at increased risk of very preterm
      birth (odds ratio = 4.8). The corresponding risks among women aged 16 to 17 years
      at first birth were doubled (odds ratio = 2.3). The influence of maternal age on
      risks of moderately preterm birth was similar, although the age-related risks
      were lower. At second birth, risks of preterm birth were reduced in all age
      groups. However, mothers who were 17 years or less at first birth, faced,
      compared with mothers aged 20-24 years, significantly larger reduction in risks
      of very and moderately preterm birth. CONCLUSIONS: Our results suggest that there
      may be a biological effect of very young maternal age, affecting foremost very
      preterm birth.

PMID- 11467699
TI  - Anatomical and functional changes in the lower urinary tract during pregnancy.
AB  - OBJECTIVE: To assess the prevalence and the development of urinary incontinence
      in nulliparous pregnant women, both subjectively and objectively, and to
      investigate the relation of incontinence with the mobility of the urethro-vesical
      junction measured by perineal ultrasound. DESIGN: A prospective longitudinal
      study. SETTING: University Hospital and Martini Hospital Groningen, the
      Netherlands. POPULATION: A cohort of 117 nulliparous pregnant women and 27
      nulliparous non-pregnant controls. METHODS: Urinary incontinence was measured by
      a questionnaire and by a 24-hour pad test. The position of the urethro-vesical
      junction and its mobility were measured by perineal ultrasound. MAIN OUTCOME
      MEASURE: Prevalence of urinary incontinence; mobility of the urethro-vesical
      junction, indicated by the displacement/pressure coefficient. RESULTS: Up to 35%
      of the women reported urinary incontinence in pregnancy, and 20% of the women had
      a positive pad test. The angle of the urethro-vesical junction angle at rest and
      the displacement/pressure coefficient during coughing showed a significant
      increasing trend during pregnancy, but no changes were seen during the Valsalva
      manoeuvre. No relationship was found between subjective and objective
      incontinence data and the position and mobility of the urethro-vesical junction.
      CONCLUSION: The prevalence of incontinence in nulliparous women as found by the
      pad test was significantly higher in pregnancy (20%) than in the non-pregnant
      control group (4%). Perineal ultrasound of the urethrovesical junction showed
      lowering of the pelvic floor occurring as early as 12-16 weeks of pregnancy.
      Serial measurements of the displacement/pressure coefficient suggest that the
      dynamic characteristics of the connective tissues of the pelvic floor remain
      unaltered,whereas a significant decrease in pelvic floor muscle contraction
      occurs. Since no relation was found between measurements of the urethro-vesical
      junction and incontinence, urinary incontinence in pregnancy is most likely
      explained by other factors.

PMID- 11467700
TI  - Impact of pneumoperitoneum on visceral metastasis rate and survival. Results in
      two ovarian cancer models in rats.
AB  - OBJECTIVE: To compare the impact of CO2 laparoscopy, gasless laparoscopy, and
      midline laparotomy on the development of distant metastases and on survival in
      two ovarian carcinoma models. DESIGN: A prospective randomised study in rats.
      MATERIAL: and methods Two ovarian cancer xenografts were obtained by
      intraperitoneal injection of IGR-OV1 or NIH-OVCAR-3 cells. Experimental surgical
      procedures were performed on day 7 (IGR-OVI model) or day 14 (NIH: OVCAR-3 model)
      after intraperitoneal injection: CO2 laparoscopy (pneumoperitoneum (PNP) with
      unheated CO2 at a pressure of 8 mmHg for 1 hour); gasless laparoscopy (consisting
      in abdominal wall expansion by a balloon for 1 hour); midline laparoscopy
      (consisting in bowel exteriorisation on a mesh for one hour following xyphopubic
      laparotomy). The control group underwent general anaesthesia alone. The animals
      were killed by CO2 inhalation as soon as they became moribund. MAIN OUTCOME
      MEASURES: Pathological examination was carried out on the liver, lungs and pleura
      as well as the retroperitoneal nodes. Survival was determined from the time of
      surgery to the sacrifice of the animal. Statistical analysis used ANOVA, Fisher
      exact test, Bonferonni method and the log-rank test. RESULTS: In the IGR-OV1
      model, distant metastases were rare, and were not promoted by CO2 laparoscopy.
      With the NIH: OVCAR-3 model, pleural, pulmonary and para-aortic metastases were
      not enhanced by CO2 PNP when compared with other approaches. Conversely, midline
      laparotomy and laparoscopy significantly increased liver involvement when
      compared with gasless laparoscopy (P = 0.04 and P = 0.008). Survival was
      comparable no matter what kind of surgery had been performed in the IGR-OV1 model
      (P = 0.7) or in the NIH: OVCAR-3 model (P = 0.5). CONCLUSIONS: CO2 laparoscopy
      had a minor impact on distant and nodal metastases in the two models. Similarly,
      survival was similar for all surgical groups.

PMID- 11467701
TI  - Lowering the doses of mifepristone and gameprost for early abortion: a randomised
      controlled trial. World Health Organization Task Force on Post-ovulatory Methods
      for Fertility Regulation.
AB  - OBJECTIVE: To test the efficacy of lower doses of mifepristone and gemeprost for
      medical induction of early abortion. DESIGN: Randomised controlled trial.
      Participants were blinded as to the therapy and physicians to the dose of
      mifepristone. SETTING: Thirteen hospital gynaecological units in different
      continents. PARTICIPANTS: 1,224 healthy pregnant women requesting medical
      abortion at <57 days from last menses. INTERVENTION: Random allocation to one of
      four regimens: mifepristone 50 mg by mouth followed by either 0.5 mg or 1.0 mg
      gemeprost vaginally on day 3; mifepristone 200 mg by mouth followed by either 0.5
      mg or 1.0 mg gemeprost vaginally. We concealed the allocation sequence from
      clinicians enrolling participants, and maintained double blinding throughout.
      MAIN OUTCOME MEASURES: Incidence of complete abortion; subordinate outcome
      measures included side effects such as vomiting and fall in haemoglobin, as well
      as the need for emergency curettage and blood transfusion. RESULTS: The success
      rate was significantly related to the dose of mifepristone. The relative risk of
      failure to have a complete abortion with the lower dose of mifepristone was 1.6
      (95% CI: 1.1-2.3) times that with the higher dose. The relative risk of failure
      with the lower dose of gemeprost (1.3; 95% CI: 0.9-1.8) did not reach statistical
      significance. CONCLUSIONS: A single dose of mifepristone 50 mg followed by
      gemeprost is inadequate for early medical abortion. There was no significant
      difference in side effects between the four treatment groups.

PMID- 11467702
TI  - Declining trend in major gynaecological surgery in The Netherlands during 1991
      1998. Is there an impact on surgical skills and innovative ability?
AB  - OBJECTIVES: To assess the number of major surgical procedures in gynaecology over
      a period of eight years in The Netherlands and to detect possible trends.
      Relevance of the trends and the possible impact on surgical skills and on
      innovative ability are discussed. DESIGN: Observational study. SETTING: Hospital
      care in The Netherlands. SAMPLE: Data from a national hospital discharge
      database, from all 119 hospitals in The Netherlands. METHODS: When a patient is
      discharged from the hospital. data on the diagnosis and treatment are registered
      by local medical officers and administrators. Registration of surgical procedures
      is based on the International Classification of Procedures in Medicine (ICPM, WHO
      1978), the so-called WCC-standard. All hospitals but one (a cancer centre) in The
      Netherlands participate in this registration, resulting in 99.3% of all
      admissions. Data on gynaccological manpower were obtained from the Dutch College
      of Obstetricians and Gynaecologists. In order to standardise the frequency
      numbers per 1,000 women, yearly data of the female population according to age
      were obtained from the Central Office for Population Statistics. RESULTS: The
      female population aged 20 years of age and older increased 3% between 1991 and
      1998, from 5.8 million to 6.0 million. In the same period the number of
      gynaecologists grew from 604 to 625, also an increase of 3%. The total number of
      hysterectomies dropped from 21,433 in 1991 to 16,320 (-24 %) in 1998 (chi2 for
      trend 1,245.1. P < 0.001) Surgery of the uterine cavity, either performed
      hysteroscopically or blind, increased from 311 to 1,958 (+ 625%) cases per year
      (chi2 for trend 2,459.2, P < 0.001). No trend has been detected in the numbers of
      adnexal operations, including surgical treatment of tubal pregnancy (tubotomy or
      tubectomy). In 1998, 12% of all ovarian surgery and 28% of all surgery for
      ectopic pregnancies was performed laparoscopically. Surgery for female urinary
      incontinence experienced a strong decline of 46% in the studied period. The
      frequency of vaginal repair decreased with 1354 (-16%) cases. The abdominal
      prolapse surgery (abdominal sacral colpopexy, obliteration of the Douglas pouch)
      is steadily increasing, although the absolute numbers are small. In 1998 seven
      hundred and forty-three women underwent an abdominal approach of their prolapse
      repair, compared with 7239 that had the vaginal repair. CONCLUSIONS: The
      declining trend of major gynaecological surgery in combination with the
      increasing number of gynaecologists will result in more difficulty for
      gynaecologists to acquire and maintain surgical skills and may therefore affect
      their ability to innovate within the surgical profession.

PMID- 11467703
TI  - Endometrial laser intrauterine thermotherapy for the treatment of dysfunctional
      uterine bleeding: the first British experience.
AB  - Forty patients due to undergo endometrial ablation as a treatment for
      dysfunctional uterine bleeding were recruited to assess the efficacy and safety
      of endometrial laser intrauterine thermo-therapy using the gynelase. At 12 months
      the average menstrual score reduction was 88%, the amenorrhoea rate was 70%, and
      the hypomenorrhoea rate 16%. Four women (10%) have had a hysterectomy for
      persistent menorrhagia, and one (3%) for pelvic pain. One patient (3%) has had a
      further endometrial laser ablation. There were no major complications. and 34
      patients (85%) were most satisfied with the treatment. The system is easy to use
      and has a short learning curve.

PMID- 11467704
TI  - The predictive value of serum 1,5-anhydro-D-glucitol in pregnancies at increased
      risk of gestational diabetes mellitus and gestational impaired glucose tolerance.
AB  - The objective of the study was to determine the efficacy of 1,5-anhydro-D
      glucitol (1,5 AG) for the prediction of gestational diabetes and gestational
      impaired glucose tolerance (GIGT). One hundred and eighty-five pregnant women
      with epidemiological risk factors of gestational diabetes or GIGT underwent 75 g
      oral glucose tolerance test and plasma 1,5 AG assay at 26 to 28 weeks of
      gestation. There was no significant difference in plasma 1,5 AG either before or
      after an oral glucose load. The area under the receiver operator characteristic
      curve for 1,5 AG was only 0.485 which implies that 1,5 AG is a poor predictor of
      GIGT or gestational diabetes.

PMID- 11467705
TI  - Use of enoxaparin in a pregnant woman with a mechanical heart valve prosthesis.

PMID- 11467706
TI  - Pregnancy in primary biliary cirrhosis complicated by portal hypertension: report
      of a case and review of the literature.

PMID- 11467707
TI  - Transurethral penetration of a tension-free vaginal tape.

PMID- 11467708
TI  - Sentinel lymph node detection in locally recurrent carcinoma of the vulva.

PMID- 11467709
TI  - A randomised controlled pilot study of the management of gestational impaired
      glucose tolerance.

PMID- 11467710
TI  - Maternal thyroid disease: a risk factor for newborn encephalopathy.

PMID- 11467711
TI  - Levonorgestrel-releasing (20mcg/day) intrauterine systems (Mirena) compared with
      other methods of reversible contraceptives.

PMID- 11467712
TI  - Does histological incomplete excision of cervical intraepithelial neoplasia
      following large excision of transformation zone increase recurrence rates? A six
      year cytological follow up.

PMID- 11467713
TI  - Does histological incomplete excision of cervical intraepithelial neoplasia
      following large excision of transformation zone increase recurrence rates? A six
      year cytological follow up.

PMID- 11467714
TI  - Does histological incomplete excision of cervical intraepithelial neoplasia
      following large excision of transformation zone increase recurrence rates? A six
      year cytological follow up.

PMID- 11467715
TI  - The relationship between increased folate stetabolism and the increased
      requirement for folate in pregnancy.

PMID- 11467716
TI  - The management of menorrhagia--SMART study (Satisfaction with Mirena and
      Ablation: a Randomised Trial).

PMID- 11467717
TI  - Postpartum depression: identification of women at risk.

PMID- 11467718
TI  - Naegele's rule: a reappraisal.

PMID- 11467719
TI  - Vault prolapse and rectocele assessment of repair using sacrocolpopexy with mesh
      interposition.

PMID- 11467720
TI  - A comparison of bladder neck movement and elevation after tension free vaginal
      tape and colposuspension.

PMID- 11467721
TI  - A randomised controlled trial of flexibility in routine antenatal care.

PMID- 11467722
TI  - Acid and alkaline treatments for enhancing the growth of rhizobia in sludge.
AB  - Wastewater sludges have been proposed as an effective media for the production of
      rhizobia. The effect of total suspended solid (TSS) concentrations and
      pretreatments of sludge on the growth of Sinorhizobium meliloti were
      investigated. Acid (pH 2.0-6.0 obtained with H2SO4) and alkaline (50-200
      mequiv.wt./L of NaOH) treatments were applied to enhance the biodegradability of
      primary (0.325%-3.2% TSS obtained by dilution of original sample) and secondary
      (0.2%-0.4% TSS obtained by concentration of original sample) sludges. In primary
      sludge without pretreatment, the highest cell count (11.10 x 10(9) cfu/mL) was
      obtained with 1.3% TSS. However, a maximum cell count of 13.00 x 10(9) cfu/mL was
      reached using an acid treatment of pH 2.0 and a 0.325% TSS concentration.
      Moreover, the alkaline treatment with 100 mequiv.wt./L of NaOH and 0.65% TSS
      increased the cell yield to 21.00 x 10(9) cfu/mL. For secondary sludge without
      pretreatment, no enhancement of growth was observed while increasing TSS
      concentration. This may be due to the increase of inhibitory substances, such as
      heavy metals, and of the Ca and Mg concentrations. As in primary sludge, some
      acid and alkaline treatments of secondary sludge tend to improve the cell count
      of S. meliloti. However, the highest value of 9.80 x 10(9) cfu/mL obtained with
      0.4% TSS at pH 2.0 was lower than that obtained with primary sludge. It was also
      observed that S. meliloti grown in treated sludges maintained its capacity to
      nodulate alfalfa.

PMID- 11467723
TI  - Erosion of root epidermal cell walls by Rhizobium polysaccharide-degrading
      enzymes as related to primary host infection in the Rhizobium-legume symbiosis.
AB  - A central event of the infection process in the Rhizobium-legume symbiosis is the
      modification of the host cell wall barrier to form a portal of entry large enough
      for bacterial penetration. Transmission electron microscopy (TEM) indicates that
      rhizobia enter the legume root hair through a completely eroded hole that is
      slightly larger than the bacterial cell and is presumably created by localized
      enzymatic hydrolysis of the host cell wall. In this study, we have used
      microscopy and enzymology to further clarify how rhizobia modify root epidermal
      cell walls to shed new light on the mechanism of primary host infection in the
      Rhizobium-legume symbiosis. Quantitative scanning electron microscopy indicated
      that the incidence of highly localized, partially eroded pits on legume root
      epidermal walls that follow the contour of the rhizobial cell was higher in host
      than in nonhost legume combinations, was inhibited by high nitrate supply, and
      was not induced by immobilized wild-type chitolipooligosaccharide Nod factors
      reversibly adsorbed to latex beads. TEM examination of these partially eroded,
      epidermal pits indicated that the amorphous, noncrystalline portions of the wall
      were disrupted, whereas the crystalline portions remained ultrastructurally
      intact. Further studies using phase-contrast and polarized light microscopy
      indicated that (i) the structural integrity of clover root hair walls is
      dependent on wall polymers that are valid substrates for cell-bound
      polysaccharide-degrading enzymes from rhizobia, (ii) the major site where these
      rhizobial enzymes can completely erode the root hair wall is highly localized at
      the isotropic, noncrystalline apex of the root hair tip, and (iii) the
      degradability of clover root hair walls by rhizobial polysaccharide-degrading
      enzymes is enhanced by modifications induced during growth in the presence of
      chitolipooligosaccharide Nod factors from wild-type clover rhizobia. The results
      suggest a complementary role of rhizobial cell-bound glycanases and
      chitolipooligosaccharides in creating the localized portals of entry for
      successful primary host infection.

PMID- 11467724
TI  - Selection of several classes of mimosine-degradation-defective Tn3Hogus-insertion
      mutants of Rhizobium sp. strain TAL1145 on the basis of mimosine-inducible GUS
      activity.
AB  - Rhizobium sp. strain TAL1145 that nodulates Leucaena leucocephala degrades
      mimosine, a toxin produced by this tree legume. A cosmid clone, pUHR263,
      containing approximately 25 kb cloned DNA was isolated by plating Escherichia
      coli cells containing the cosmid clone library of TAL1145 on a minimal medium in
      which 3-hydroxy-4-pyridone (HP), a degradation product of mimosine, was used as
      the source of nitrogen. Cosmid pUHR263 was mutagenized by random insertions of
      Tn3Hogus, a transposon that makes transcriptional gus fusions when it is inserted
      in a gene in the correct orientation. Various pUHR263::Tn3Hogus derivatives that
      showed mimosine-inducible or mimosine-repressible GUS activities when transferred
      to the Rhizobium sp. strain TAL1145 were selected. Mutants of TAL1145 were
      constructed by transferring these Tn3Hogus insertions into the TAL1145 chromosome
      through double-homologous recombination. These mutants were classified into five
      classes on the basis of defects in mimosine degradation. The growth of these
      mutants was inhibited to different extents by mimosine applied to the growth
      medium. Mimosine forms a red-colored Fe-mimosine complex when FeCI3 is added to
      the medium. The inhibitory effect of Fe-mimosine on growth of the mutants was
      much less than that of mimosine.

PMID- 11467725
TI  - Analysis of the genetic region encoding a novel rhizobiocin from Rhizobium
      leguminosarum bv. viciae strain 306.
AB  - Cross-testing of a number of strains of Rhizobium leguminosarum for bacteriocin
      production revealed that strain 306 produced at least two distinct bacteriocins.
      Further analysis involving plasmid transfer to Agrobacterium and other hosts
      demonstrated that there were bacteriocin determinants on plasmids pRle306b and
      pRle306c, as well as a third bacteriocin. The bacteriocin encoded by pRle306b was
      indistinguishable from the bacteriocin encoded by strain 248, whereas the
      bacteriocin encoded by plasmid pRle306c had a distinctive spectrum of activity
      against susceptible strains, as well as different physical properties from other
      bacteriocins that we have studied in our lab. Two mutants altered in production
      of the pRle306c bacteriocin were generated by transposon Tn5 mutagenesis, and the
      DNA flanking the transposon inserts in these mutants was cloned and
      characterized. DNA sequence analysis suggested that the pRle306c bacteriocin was
      a large protein belonging to the RTX family, and that a type I secretion system
      involving an ABC type transporter was required for export of the bacteriocin. A
      mutant unable to produce this bacteriocin was unaltered in its competitive
      properties, both in broth and in nodulation assays, suggesting that the
      bacteriocin may not play a major role in determining the ecological success of
      this strain.

PMID- 11467726
TI  - Identification of a system that allows a Rhizobium tropici dctA mutant to grow on
      succinate, but not on other C4-dicarboxylates.
AB  - A defined insertion mutant of a gene encoding a homolog of the rhizobial C4
      dicarboxylate permease (dctA) was constructed in Rhizobium tropici strain
      CIAT899. This mutant (GA1) was unable to grow on fumarate or malate; however, in
      contrast with other rhizobial dctA mutants, it retained a limited ability to grow
      on succinate with ammonia as a nitrogen source. Our results suggest the presence
      of a novel succinate-specific transport system in R. tropici. Biochemical
      characterization indicated that this alternative transport system in GAI is
      active and dependent on an energized membrane. It was also induced by succinate
      and aspartate, and was repressed by glucose and glycerol. Bean plants inoculated
      with GA1 showed a reduced nitrogen-fixing ability, achieving only 29% of the
      acetylene reduction activity determined in CIAT899 strain nodules, 33 days after
      inoculation. Also, bean plants inoculated with GA1 had reduced shoot dry weight
      compared with plants inoculated with the wild-type strain.

PMID- 11467727
TI  - Characterization of soybean bradyrhizobia for which serogroup affinities have not
      been identified.
AB  - The USDA, ARS National Rhizobium Germplasm Collection contains 143 accessions of
      slow-growing soybean strains among which there are 17 distinct serological
      groups. However, 11 strains appear to have no serological affinity with the 17
      serogroups. Therefore, we determined whether these strains were diverse and
      examined their phylogenetic placement. Nine strains formed nitrogen-fixing
      symbioses with soybean indicating that these accessions were not contaminants. We
      concluded from results of amplified fragment length polymorphism (AFLP) analysis,
      using 3 selective primers with 8 strains, that they were genetically dissimilar.
      Nine strains were examined for their fatty acid composition using fatty acid
      methyl ester (FAME) derivatives. The FAME results with 5 strains and serotype
      strains of Bradyrhizobium elkanii were similar, while results with each of the
      remaining 2 pairs were either similar to the type strain of Bradyrhizobium
      japonicum (USDA 6) or to USDA 110. Evolutionary history of 9 strains was
      reconstructed from sequence divergence of a combination of the complete 16S rRNA
      gene, the internally transcribed spacer region, and about 400 bases of the 5' end
      of the 23S rRNA gene. Placement of 5 strains was nested within B. elkanii, 2 with
      USDA 110, and the other 2 with USDA 6. We concluded that soybean isolates that
      cannot be placed within one of the 17 established serogroups are phenotypically
      and genetically as diverse as the serotype strains.

PMID- 11467728
TI  - Diversity in the rhizobia associated with Phaseolus vulgaris L. in Ecuador, and
      comparisons with Mexican bean rhizobia.
AB  - Common beans (Phaseolus vulgaris L.) have centers of origin in both Mesoamerica
      and Andean South America, and have been domesticated in each region for perhaps
      5000 years. A third major gene pool may exist in Ecuador and Northern Peru. The
      diversity of the rhizobia associated with beans has also been studied, but to
      date with an emphasis on the Mesoamerican center of origin. In this study we
      compared bean rhizobia from Mexico and Andean South America using both phenotypic
      and phylogenetic approaches. When differences between the rhizobia of these two
      regions were shown, we then examined the influence of bean cultivar on the most
      probable number (MPN) count and biodiversity of rhizobia recovered from different
      soils. Three clusters of bean rhizobia were distinguished using phenotypic
      analysis and principal-component analysis of Box AIR-PCR banding patterns. They
      corresponded principally to isolates from Mexico, and the northern and southern
      Andean regions, with isolates from southern Ecuador exhibiting significant
      genetic diversity. Rhizobia from Dalea spp., which are infective and effective on
      beans, may have contributed to the apparent diversity of rhizobia recovered from
      the Mesoamerican region, while the rhizobia of wild Phaseolus aborigineus from
      Argentina showed only limited similarity to the other bean rhizobia tested. Use
      of P. vulgaris cultivars from the Mesoamerican and Andean Phaseolus gene pools as
      trap hosts did not significantly affect MPN counts of bean rhizobia from the
      soils of each region, but did influence the diversity of the rhizobia recovered.
      Such differences in compatibility of host and Rhizobium could be a factor in the
      poor reputation for nodulation and N2 fixation in this crop.

PMID- 11467729
TI  - Hopanoid lipids in Frankia: identification of squalene-hopene cyclase gene
      sequences.
AB  - In Frankia, the microsymbiont in actinorhizal root nodules, nitrogen fixation
      takes place in specialized structures called vesicles. The lipidic vesicle
      envelope forms a barrier to oxygen diffusion, an essential part of the
      nitrogenase oxygen protection system. We have shown previously that the vesicle
      envelope is composed primarily of two species of hopanoid lipids, sterol-like
      molecules that are synthesized in a wide range of bacteria, including Frankia,
      several cyanobacteria, and rhizobia. The levels of hopanoid found in Frankia are
      among the highest of any organism known to date. Here we report that short (328
      bp) DNA sequences from several strains of Frankia spp. have been identified that
      are homologous to a portion of the coding region of squalene-hopene cyclase (shc)
      genes. The fragments and corresponding polymerase chain reaction (PCR) primers
      can be used in phylogenetic comparisons of Frankia, both within Frankiaceae and
      among bacteria that synthesize hopanoids.

PMID- 11467730
TI  - Modification of the protein expression pattern induced in the nitrogen-fixing
      actinomycete Frankia sp. strain ACN14a-tsr by root exudates of its symbiotic host
      Alnus glutinosa and cloning of the sodF gene.
AB  - Two-dimensional (2-D) polyacrylamide gel electrophoresis was used to detect
      proteins induced in Frankia sp. strain ACN14a-tsr by root exudates of its
      symbiotic host, Alnus glutinosa. The 5 most prominent proteins were purified from
      2-D gels and characterized by N-terminal sequencing. All of these proteins had a
      high percentage of similarity with known stress proteins. One protein match was
      the Fe superoxide dismutase (Fe-SOD), another was a tellurite resistance protein
      (Ter), the third was a bacterioferritin comigratory protein (Bcp); and two
      matches, differing only by their isoelectric point, were the same small heat
      shock protein (Hsp), a major immune reactive protein found in mycobacteria. This
      suggests that the symbiotic microorganism Frankia, first responds with a normal
      stress response to toxic root products of its symbiotic host plant. To confirm
      its identity, the gene corresponding to the Fe-SOD protein, sodF was isolated
      from a genomic library by a PCR-approach and sequenced. It is the first stress
      response gene characterized in Frankia.

PMID- 11467731
TI  - Biotransformation and partial mineralization of the explosive 2,4,6
      trinitrotoluene (TNT) by rhizobia.
AB  - Three strains, T10, B5, and M8, each belonging to a different species of the
      family Rhizobiaceae and isolated from atrazine-contaminated soils, were tested
      for their ability to transform 2,4,6-trinitrotoluene (TNT) (50 microg x mL(-1))
      in liquid cultures using glucose as the C-source. All three strains were able to
      transform TNT to hydroxylaminodinitrotoluenes (2-HADNT, 4-HADNT),
      aminodinitrotoluenes (2-ADNT, 4-ADNT), and diaminonitrotoluene (2,4-DANT). The
      transformation was significantly faster in the presence of glutamate.
      Furthermore, the major metabolites that accumulated in cultures were 2-ADNT with
      glucose, and 4-ADNT with glutamate plus glucose. Rhizobium trifolii T10 was also
      tested for its ability to transform high levels of TNT (approximately 350 microg
      x mL(-1)) in a soil slurry. Almost 60% of the TNT was transformed within 2 days
      in bioaugmented soil slurries, and up to 90% when cultures were supplemented with
      glucose and glutamate. However, mineralization was minimal in all cases, less
      than 2% in 78 days. This is the first report on the degradation of TNT by
      rhizobial strains, and our findings suggest that rhizobia have the potential to
      play an important role in the safe decontamination of soils and sites
      contaminated with TNT if bioaugmentation with rhizobia is shown to have no
      ecotoxicological consequence.

PMID- 11467732
TI  - Temporal effects on the composition of a population of Sinorhizobium meliloti
      associated with Medicago sativa and Melilotus alba.
AB  - An assessment was made of the impact of temporal separation on the composition of
      a population of Sinorhizobium meliloti associated with Medicago sativa (alfalfa)
      and Melilotus alba (sweet clover) grown at a single site that had no known
      history of alfalfa cultivation. Root nodules were sampled on six occasions over
      two seasons, and a total of 1620 isolates of S. meliloti were characterized on
      the basis of phage sensitivity using 16 typing phages. Plant infection tests
      indicated that symbiotic S. meliloti were deficient in the soil at the time of
      planting and that these bacteria were present at low density during the first
      season (<10(2)/g of soil); in the second season numbers increased markedly to
      about 10(5)/g of soil. Overall, 37 and 51 phage types, respectively, were
      encountered among the nodule isolates from M. sativa and M. alba. The data
      indicate significant temporal shifts in the frequency and diversity of types
      associated with the two legume species. Apparent temporal variation with respect
      to the frequency of types appeared largely unpredictable and was not attributable
      to any one sampling time. The results indicate an apparent reduction in
      phenotypic diversity over the course of the experiment. Differential host plant
      selection of specific types with respect to nodule occupancy was indicated by
      significant interactions between legume species and either the frequency or
      diversity of phage types. Isolates from M. sativa that were resistant to lysis by
      all typing phages (type 14) were unusual in that they were predominant on this
      host at all sampling times (between 53% and 82% nodule occupancy) and were
      relatively homogeneous on the basis of DNA hybridization with 98% of the isolates
      analysed sharing the same nod EFG hybridization profile. In contrast, those
      isolates from M. alba comprising type 14 were encountered at low total frequency
      (2%) and were genetically heterogeneous on the basis of Southern hybridization.
      The implications of the observed temporal and host plant variation for ecological
      studies are discussed.

PMID- 11467733
TI  - Regulation of nod factor sulphation genes in Rhizobium tropici CIAT899.
AB  - Rhizobium tropici CIAT899 is a tropical symbiont able to nodulate various legumes
      such as Leucaena, Phaseolus, and Macroptilium. Broad host range of this species
      is related to its Nod factors wide spectrum. R. tropici contains Nod factors
      sulphation nod genes, nodHPQ genes, which control nodulation efficiency in
      Leucaena. To study nodHPQ regulation, we carried out different interposon
      insertions in its upstream region. One of these generated interruptions, nodI
      mutant produced nonsulphated Nod factors suggesting a possible dependence of
      these genes on nodI upstream region. Moreover, analysis results of lacZ
      transcriptional fusions with these genes in symbiotic plasmid showed dependence
      of these genes on NodD protein. In order to determine nodHPQ organization, we
      studied the effect of interposon insertion upstream of each lacZ transcriptional
      fusion, and the data obtained was used to indicate that nodHPQ belong to the
      nodABCSUIJ operon. However, comparison between nodP::lacZ beta-galactosidase
      activity in the symbiotic plasmid and in the pHM500 plasmid (containing nodHPQ
      genes) suggested constitutive expression in free living, and flavonoid inducible
      expression in symbiotic conditions. Constitutive nodHPQ expression may play a
      role in bacterial house-keeping metabolism. On the other hand, the transference
      of R. tropici nodHPQ genes to other rhizobia that do not present sulphated
      substitutions demonstrated that NodH protein sulphotransference is specific to C6
      at the reducing end.

PMID- 11467734
TI  - Comparative strain typing of Rhizobium leguminosarum bv. viciae natural
      populations.
AB  - 372 natural isolates of Rhizobium leguminosarum bv. viciae, rescued from nodules
      of pea plants grown in an agricultural field in northern Italy, were analyzed by
      different methods. Three DNA-based fingerprinting techniques were lined up to
      compare their relative degree of resolution and possible advantages of each
      approach. The methods included (i) Eckhardt gel plasmid profiles, (ii) pulsed
      field gel electrophoresis (PFGE) of genomic large fragment digests, and (iii)
      random amplified polymorphic DNA (RAPD) profiles, generated with arbitrary
      primers. The scheme also involved the isolation of a number of different isolates
      per nodule to estimate the level of intra-nodular variability. It was therefore
      possible to evaluate the frequency of double and multiple occupancies, and the
      proportion of the alternative profiles sharing the same nodule, generally
      resulting in a numerically dominant, main representative accompanied by a
      secondary one with a slightly different fingerprint. This finding revealed that
      the different profiles within a nodule are normally due to bacteria derived from
      the same single invader following genetic alterations possibly occurred during
      infection, e.g., by plasmid loss. The analysis of 31 nodules revealed 16
      different patterns, representing the most frequently occurring nodulation
      proficient isolates of the natural soil examined, five of which were found with
      frequencies around 15%. The sensitivity of the methods in differentiating
      isolates was compared. The relatedness of the different natural rhizobial
      isolates was investigated by densitometrical gel analysis of the fingerprints,
      allowing a comparison of the results. One of the most interesting conclusions was
      that the degree of information yielded by the plasmid gel profiling alone,
      carried out by simple visual inspection without software-aided analyses, was
      surprisingly high, as it enabled a placement of the isolates, whose accuracy, in
      terms of relatedness, was subsequently confirmed by each of the two genomic
      methods.

PMID- 11467735
TI  - Rhizobial survival and nodulation of chickpea as influenced by fungicide seed
      treatment.
AB  - The survival of Rhizobium ciceri on chickpea (Cicer arietinum cv. Myles) seed,
      treated separately with 1 of 4 commercial fungicides, i.e., Apron, Arrest 75W,
      Crown, or Captan, was examined under laboratory conditions using standard serial
      dilution and plate count techniques. The resulting effects of fungicide-Rhizobium
      interactions on nodulation, N2 fixation, and plant growth were assessed in a
      controlled environment. Fungicide treatment decreased the number of viable
      rhizobia on the seed. In general, the toxicity of the fungicides in terms of
      rhizobial viability increased in the following order: Control = Crown < Arrest =
      Apron < Captan. Although Crown had no effect on rhizobial viability assessed
      under laboratory conditions, it significantly reduced nodulation, percent N
      derived from the atmosphere (%Ndfa), and shoot dry matter. Seed treated with
      Arrest and Captan decreased nodule dry weight and %Ndfa, but only Arrest reduced
      dry matter yield. Apron had no effect on any of the parameters measured at the
      early pod-filling stage and was compatible with the chickpea inoculum used in
      this study.

PMID- 11467736
TI  - Chromatin: mysteries solved?
AB  - Over the past few years we have seen enormous progress in uncovering the critical
      roles that chromatin structure has on the control of gene expression, the
      regulation of developmental processes, and the control of cell cycle checkpoints.
      No longer is chromatin research the "last bastion of scoundrels." The recent
      intensity of chromatin research, however, might lead a young scientist to
      conclude that the field is saturated or that all the big mysteries have been
      solved. This view could not be further from the truth! Here I briefly outline
      four areas of chromatin research where new paradigms and mysteries are still
      waiting to be discovered.

PMID- 11467737
TI  - Higher-order folding of heterochromatin: protein bridges span the nucleosome
      arrays.
AB  - In interphase eukaryotic nuclei, chromatin is divided into two morphologically
      distinct types known as heterochromatin and euchromatin. It has been long
      suggested that the two types of chromatin differ at the level of higher-order
      folding. Recent studies have revealed the features of chromatin 3D architecture
      that distinguish the higher-order folding of repressed and active chromatin and
      have identified chromosomal proteins and their modifications associated with
      these structural transitions. This review discusses the molecular and structural
      determinants of chromatin higher-order folding in relation to mechanism(s) of
      heterochromatin formation and genetic silencing during cell differentiation and
      tissue development.

PMID- 11467738
TI  - Class II histone deacetylases: structure, function, and regulation.
AB  - Acetylation of histones, as well as non-histone proteins, plays important roles
      in regulating various cellular processes. Dynamic control of protein acetylation
      levels in vivo occurs through the opposing actions of histone acetyltransferases
      and histone deacetylases (HDACs). In the past few years, distinct classes of
      HDACs have been identified in mammalian cells. Class I members, such as HDAC1,
      HDAC2, HDAC3, and HDAC8, are well-known enzymatic transcriptional corepressors
      homologous to yeast Rpd3. Class II members, including HDAC4, HDAC5, HDAC6, HDAC7,
      and HDAC9, possess domains similar to the deacetylase domain of yeast Hdal.
      HDAC4, HDAC5, and HDAC7 function as transcriptional corepressors that interact
      with the MEF2 transcription factors and the N-CoR, BCoR, and CtBP corepressors.
      Intriguingly, HDAC4, HDAC5, and probably HDAC7 are regulated through subcellular
      compartmentalization controlled by site-specific phosphorylation and binding of
      14-3-3 proteins; the regulation of these HDACs is thus directly linked to
      cellular signaling networks. Both HDAC6 and HDAC9 possess unique structural
      modules, so they may have special biological functions. Comprehension of the
      structure, function, and regulation of class II deacetylases is important for
      elucidating how acetylation regulates functions of histones and other proteins in
      vivo.

PMID- 11467739
TI  - CBP, a transcriptional coactivator and acetyltransferase.
AB  - The CREB binding protein (CBP) was first identified as a protein that
      specifically binds to the active phosphorylated form of the cyclic-AMP response
      element binding protein (CREB). CBP was initially defined as a transcriptional
      coactivator that, as a result of its large size and multiple protein binding
      domain modules, may function as a molecular scaffold. More recently, an
      acetyltransferase activity, both of histones and nonhistones, has been found to
      be essential for transactivation. In this review, we will discuss the current
      understanding of the acetyltransferase specificity and activity of the CBP
      protein and how it may function to coactivate transcription. We will also examine
      the regulation of the CBP histone acetyltransferase activity in the cell cycle,
      by signal-transduction pathways and throughout development.

PMID- 11467740
TI  - The integration of tissue structure and nuclear function.
AB  - Living cells can filter the same set of biochemical signals to produce different
      functional outcomes depending on the deformation of the cell. It has been
      suggested that the cell may be "hard-wired" such that external forces can mediate
      internal nuclear changes through the modification of established, balanced,
      internal cytoskeletal tensions. This review will discuss the potential of
      subnuclear structures and nuclear chromatin to participate in or respond to
      transduction of mechanical signals originating outside the nucleus. The
      mechanical interactions of intranuclear structure with the nuclear lamina will be
      examined. The nuclear lamina, in turn, provides a structural link between the
      nucleus and the cytoplasmic and cortical cytoskeleton. These mechanical couplings
      may provide a basis for regulating gene expression through changes in cell shape.

PMID- 11467741
TI  - Phosphorylation of histone variant regions in chromatin: unlocking the linker?
AB  - Histone variants illuminate the behavior of chromatin through their unique
      structures and patterns of postsynthetic modification. This review examines the
      literature on heteromorphous histone structures in chromatin, structures that are
      primary targets for histone kinases and phosphatases in vivo. Special attention
      is paid to certain well-studied experimental systems: mammalian culture cells,
      chicken erythrocytes, sea urchin sperm, wheat sprouts, Tetrahymena, and budding
      yeast. A common theme emerges from these studies. Specialized, highly basic
      structures in histone variants promote chromatin condensation in a variety of
      developmental situations. Before, and sometimes after condensed chromatin is
      formed, the chromatin is rendered soluble by phosphorylation of the
      heteromorphous regions, preventing their interaction with linker DNA. A simple
      structural model accounting for histone variation and phosphorylation is
      presented.

PMID- 11467742
TI  - A compendium of the histone H1 family of somatic subtypes: an elusive cast of
      characters and their characteristics.
AB  - The last 35 years has seen a substantial amount of information collected about
      the somatic H1 subtypes, yet much of this work has been overshadowed by research
      into highly divergent isoforms of H1, such as H5. Reports from several
      laboratories in the past few years have begun to call into question some of the
      traditional views regarding the general function of linker histones and their
      heterogeneity. Hence, the impression in some circles is that less is known about
      these ubiquitous nuclear proteins as compared with the core histones. The goal of
      the following review is to acquaint the reader with the ubiquitous somatic Hls by
      categorizing them and their characteristics into several classes. The reasons for
      our current state of misunderstanding is put into a historical context along with
      recent controversies centering on the role of H1 in the nucleus. Finally, we
      propose a model that may explain the functional role of H1 heterogeneity in
      chromatin compaction.

PMID- 11467743
TI  - Histone modifications and apoptosis: cause or consequence?
AB  - Since the first description of apoptosis, genetic and biochemical studies have
      led to a greater understanding of the multiple pathways that eukaryotic cells can
      take to terminate their existence. These findings have also proven useful in
      understanding the development of various diseases such as AIDS, Alzheimer's, and
      Parkinson's and have provided potential targets for possible therapies. Despite
      all these studies, the mechanism of chromatin condensation, a morphological
      hallmark of apoptosis, remains elusive. This review describes the work to date on
      the post-translational modifications of histones during apoptosis and discusses
      the models that have been presented to explain the apoptotic condensation of
      chromatin.

PMID- 11467744
TI  - Linker histone function in chromatin: dual mechanisms of action.
AB  - Aspects pertaining to linker histone structure and function are discussed,
      including the extent to which these proteins are essential, their ability to
      regulate specific gene expression, and recent structural data that provides a
      potential molecular basis for understanding how linker histones can have both
      repressive and stimulatory effects on genomic functions in vivo.

PMID- 11467745
TI  - Influence of linker histone H1 on chromatin remodeling.
AB  - Chromatin-remodeling complexes have been a central area of focus for research
      dealing with accessing cellular DNA sequestered in chromatin. Although the linker
      histone H1 plays a major role in promoting and maintaining higher-order chromatin
      structure, it has been noticeably absent from assays utilizing chromatin
      remodeling enzymes. This review focuses on two ATP-dependent chromatin-remodeling
      complexes, Drosophila ISWI and mammalian SWI/SNF, that have been assayed using
      chromatin templates containing histone H1.

PMID- 11467746
TI  - Structural features of trinucleotide repeats associated with DNA expansion.
AB  - The mechanism of DNA expansion is not well understood. Recent evidence from
      genetic, in vivo, and in vitro studies has suggested a link between the formation
      of alternative DNA secondary structures by trinucleotide repeat tracts and their
      propensity to undergo expansion. This review will focus on structural features
      and the mechanism of expansion relevant to human disease.

PMID- 11467747
TI  - The emerging role of class II histone deacetylases.
AB  - Histone acetylation and deacetylation play essential roles in modifying chromatin
      structure and regulating gene expression in all eukaryotes. Several histone
      acetyltransferases have been identified that act as transcriptional coactivators.
      In contrast, histone deacetylases (HDACs) are part of transcriptional corepressor
      complexes. Based on their similarity to known yeast factors, the human HDACs are
      grouped into three classes. Class I HDACs are similar to the yeast
      transcriptional repressor yRPD3, while class II HDACs are related to yHDA1 and
      class III HDACs to ySIR2. In this review, we focus on the biology of class II
      HDACs. These newly discovered enzymes have been implicated in cell
      differentiation and development, and many molecular details are emerging that
      shed light on class II HDAC function and regulation. We discuss the biological
      role of these factors in the context of physiological processes.

PMID- 11467748
TI  - Linker DNA destabilizes condensed chromatin.
AB  - The contribution of the linker region to maintenance of condensed chromatin was
      examined in two model systems, namely sea urchin sperm nuclei and chicken red
      blood cell nuclei. Linkerless nuclei, prepared by extensive digestion with
      micrococcal nuclease, were compared with Native nuclei using several assays,
      including microscopic appearance, nuclear turbidity, salt stability, and trypsin
      resistance. Chromatin in the Linkerless nuclei was highly condensed, resembling
      pyknotic chromatin in apoptotic cells. Linkerless nuclei were more stable in low
      ionic strength buffers and more resistant to trypsin than Native nuclei. Analysis
      of histones from the trypsinized nuclei by polyacrylamide gel electrophoresis
      showed that specific histone H1, H2B, and H3 tail regions stabilized linker DNA
      in condensed nuclei. Thermal denaturation of soluble chromatin preparations from
      differentially trypsinized sperm nuclei demonstrated that the N-terminal regions
      of histones Sp H1, Sp H2B, and H3 bind tightly to linker DNA, causing it to
      denature at a high temperature. We conclude that linker DNA exerts a disruptive
      force on condensed chromatin structure which is counteracted by binding of
      specific histone tail regions to the linker DNA. The inherent instability of the
      linker region may be significant in all eukaryotic chromatins and may promote
      gene activation in living cells.

PMID- 11467749
TI  - Plasmapheresis in renal disease.

PMID- 11467750
TI  - Extracorporeal plasma treatment in primary and recurrent focal segmental
      glomerular sclerosis: a review.
AB  - This review summarizes the state of the art of apheresis in focal segmental
      sclerosing glomerulonephritis (FSGS) based on the current literature. FSGS is a
      major cause of nephrotic syndrome and renal insufficiency and has a high tendency
      to recur after renal transplantation. In many instances, treatment with steroids
      and/or immunosuppressive agents is without effect. Therapeutic plasma exchange
      (as well as immunoadsorption in some instances) was performed in primary (pFSGS)
      and recurrent (rFSGS) FSGS. Proteinuria could be improved and renal function was
      stabilized in 58% of rFSGS adults, in 74% of rFSGS children, and in 44% of pFSGS
      in adults. Treatment was successful if implemented early, i.e., in the stage of
      minimal change glomerulopathy before significant sclerosis had developed. This
      approach will probably be realistic only in the regular follow-up after
      transplantation. Furthermore, some patients with full-blown pFSGS were treated
      successfully in a prophylactic indication immediately prior to transplantation
      which decreased the incidence of recurrence to 26% in treated patients versus 54%
      in controls. Due to the uncontrolled study design and small patient cohorts in
      most trials, the major disadvantage of the reports currently available on the use
      of apheresis in FSGS is their low level of evidence from which the previous
      conclusions had to be drawn. Large prospective, controlled and randomized
      clinical trials are urgently needed for recommendations based on high-level
      evidence.

PMID- 11467751
TI  - Apheresis in lupus nephritis.
AB  - Systemic lupus erythematosus is a chronic autoimmune disease which commonly
      involves the kidneys. Despite great improvement in survival over the past years
      due to immunosuppressive therapy, renal failure remains an important cause of
      morbidity and mortality. In view of the pathogenesis of lupus nephritis, the use
      of less toxic and more specific ways of treatment such as the extracorporeal
      removal of pathogenetically relevant autoantibodies seems rational. On the basis
      of currently available studies, plasma exchange used alone or as an adjunct to
      conventional immunosuppressive therapy offers no clear benefit over standard
      immunosuppression in patients with active lupus nephritis and therefore cannot be
      recommended. However, although not proven, plasmapheresis might be beneficial in
      patients with acute life-threatening disease, for which high-dose
      immunosuppressive therapy may not be possible, or as an adjunct procedure for
      patients not responding to conventional therapy. Rather than the unselective
      removal of plasma, adsorption procedures allow the selective or specific removal
      of immunoglobulins, which seems to be a more reasonable approach in lupus
      nephritis. The results of the first clinical trials using different adsorption
      columns seem promising, but their use cannot be recommended until well-designed,
      case-controlled studies have been performed to prove their usefulness and cost
      effectiveness in lupus nephritis. So far, clear-cut recommendations regarding
      type of adsorption column, intensity and duration of treatment, and accompanying
      immunosuppressive treatment cannot be given.

PMID- 11467752
TI  - Therapeutic apheresis for the renal complications of multiple myeloma and the
      dysglobulinemias.
AB  - Disordered immunoglobulin synthesis can result in a variety of different types of
      renal pathology. Multiple myeloma is often associated with the overproduction of
      light chains which may result in toxicity to the renal tubules and acute renal
      failure. Patients with mixed cryoglobulinemia will have renal involvement which
      is most often in the form of a membranoproliferative glomerulonephritis. Renal
      involvement in macroglobulinemia is relatively uncommon, but IgM thrombi can be
      so voluminous as to occlude the glomerular capillary lumen. In each of these
      examples, therapeutic plasma exchange has been found to be a useful adjunct to
      the eventual chemotherapy required for the definitive treatment of these
      disorders.

PMID- 11467753
TI  - Plasmapheresis in antineutrophil cytoplasmic antibody-associated systemic
      vasculitis.
AB  - Small vessel vasculitis syndromes associated with antineutrophil cytoplasmic
      antibodies frequently cause a necrotizing and crescentic glomerulonephritis with
      the potential to progress rapidly to permanent renal failure. These conditions
      are conventionally treated with immunosuppressive drugs, but the possibility that
      humoral factors are important in their pathogenesis has led to the evaluation of
      plasmapheresis as an adjunctive therapy. Both controlled and uncontrolled studies
      have suggested that the routine addition of plasmapheresis is unnecessary.
      However, when renal function is impaired to the point that dialysis is required,
      the addition of plasma exchange increases the chance of renal recovery. The
      superiority of this approach over pulses of methylprednisolone remains to be
      confirmed.

PMID- 11467754
TI  - Extracorporeal plasma treatment in thrombotic thrombocytopenic purpura and
      hemolytic uremic syndrome: a review.
AB  - This review summarizes the state of the art of apheresis in hemolytic uremic
      syndrome (HUS) and in thrombotic thrombocytopenic purpura (TTP). Both entities
      are characterized by thrombotic microangiopathy, hemolytic anemia, and
      thrombocytopenia. While HUS often presents with renal insufficiency, cerebral
      involvement is more common in TTP. Recently, in TTP, a primary or secondary lack
      of activity of a von Willebrand factor (vWF) degrading enzyme was made
      responsible for the presence of unusually large vWF multimers causing platelet
      aggregation and thrombus formation in the microvasculature. In contrast, in
      familial HUS, a factor H deficiency with uninhibited complement activation seems
      to play a role. Therapeutic plasma exchange (TPE) using fresh frozen plasma or
      cryosupernatant as the substitution fluid is indicated in acute TTP and atypical
      HUS without antecedent diarrhea. As a rule, it will show good effectiveness,
      especially in the former entity. HUS in pregnancy should be treated by instant
      delivery whereas postpartum HUS may resolve using protracted courses of TPE. In
      contrast, in thrombotic microangiopathy after bone marrow transplantation as well
      as in HUS due to cancer, mitomycin C, or after renal transplantation, TPE is of
      questionable value and indicated only as a last resort treatment.

PMID- 11467755
TI  - Treatment of autoimmune disease: synergy between plasma exchange and intravenous
      immunoglobulins.
AB  - Therapeutic plasma exchange (PE) has been used for three decades in the treatment
      of autoimmune disease. Its mechanism of action hinges on a profound modulation of
      the immune system which is only partially understood. Removal of circulating
      immune complexes, immunoglobulins, and complement components play a role.
      Moreover, the substitution of plasma components like anti-idiotypic antibodies
      and immunoglobulins targeted against a host of antigens may add to its beneficial
      effects. Recently, intravenous administration of immunoglobulins was found to
      mimic the effects of PE in certain diseases. In fact, downregulation of Fc
      receptors, modulation of the complement activation, and anti-idiotypic
      downregulation of primary autoantibodies are mechanisms held to be responsible
      for its immunosuppressive effects. This article summarizes the effects of both
      treatment modalities, discusses their pros and cons, and makes differential
      therapeutic suggestions for the clinician of which to use in various autoimmune
      diseases.

PMID- 11467756
TI  - Apheresis technologies and clinical applications: the 2000 International
      Apheresis Registry.
AB  - The developments in apheresis technologies and techniques and their clinical
      applications worldwide are technologically, sociologically, and economically
      driven. In the past, apheresis survey statistics have highlighted both the
      differences by geographical region in clinical practices and in the types of
      technologies utilized. While a national view of apheresis is critically
      important, an international view of apheresis may be more representative overall
      of this therapeutic modality than national results that are highly dependent on
      the local economics and the available technologies. These regional differences
      have provided a basis for the scientific and clinical assessments of these
      apheresis technologies and their clinical outcomes and have impacted the
      marketing and business developments of new technologies worldwide. The results of
      the International Apheresis Registry for 2000 reporting on 39 centers on 4
      continents are presented. This survey collected data on 1,080 patients for a
      total of 15,257 treatments. Information gathered included patient demographics,
      medical history, treatment diagnoses, treatment specifics (type, methodology,
      access type, anticoagulants, drugs, equipment usage), side effects, clinical
      response, and payment provider. As in the prior International Apheresis Registry
      for 1983, the survey results highlighted the regional differences in apheresis
      usage and treatment specifics, indicating that an international overview of
      apheresis may be more representative of the impact of this therapeutic modality.

PMID- 11467757
TI  - Evidence for maximal treatment of atherosclerosis: drastic reduction of
      cholesterol and fibrinogen restores vascular homeostasis.
AB  - This article summarizes the clinical and biochemical evidence for maximal
      treatment of atherosclerosis by a simultaneous 60% to 70% reduction of plasma low
      density lipoprotein cholesterol (LDL cholesterol), fibrinogen, and lipoprotein a
      concentrations with heparin-mediated extracorporeal LDL/fibrinogen precipitation
      (HELP) apheresis and statins. Apheresis has proven efficient and safe in the
      treatment of more than 1,000 patients since 1984 and has been applied in children
      and adults for the treatment of homozygous and heterozygous familial
      hypercholesterolemia, coronary artery disease, ischemic cardiomyopathy,
      generalized atherosclerosis, or transplant-associated arteriosclerosis after
      cardiac transplantation. Simultaneous removal of the main atherogenic plasma
      compounds has an immediate impact on myocardial and peripheral vasomotion by
      increasing myocardial blood flow, coronary flow reserve, cerebral CO2-reactivity,
      and muscle oxygen tension. Removal of fibrinogen and cholesterol reduces plasma
      viscosity by 20% and erythrocyte aggregation by 60% which gives rise to applying
      the HELP apheresis in various microcirculatory disorders. Pilot studies on acute
      retinal ischemia, critical limb ischemia, and sudden hearing loss confirm this
      observation.

PMID- 11467758
TI  - Summary from the International Society for Apheresis 3rd World Congress Taipei,
      Taiwan, January 11-14, 2001.

PMID- 11467759
TI  - Regression of left ventricular mass with captopril and metoprolol, and the
      effects on glucose and lipid metabolism.
AB  - OBJECTIVE: Angiotensin II and insulin have been suggested to promote the
      development of hypertensive left ventricular (LV) hypertrophy. We compared the
      effects of captopril and metoprolol on the regression of LV mass and the relation
      to insulin sensitivity. DESIGN: 51 previously untreated non-diabetic hypertensive
      patients (mean age 51 +/- 8 years, body mass index, BMI 25.9 +/- 3.2 kg/m2,
      office blood pressure, 158/102 mmHg) were randomized to captopril or metoprolol;
      a low-dose diuretic and/or a calcium cannel antagonist were added, if needed.
      INTERVENTIONS: LV mass index (LVMI; by echocardiography) and 24-h ambulatory
      blood pressure were examined at baseline, 6 and 12 months. At baseline and 12
      months, insulin sensitivity index (MI) was calculated by a hyperinsulinemic
      euglycemic insulin clamp technique. RESULTS: Blood pressures were reduced
      similarly in both groups. LVMI (115 +/- 21 g/m2 at baseline) was reduced in both
      groups (p < 0.01), but more with captopril than with metoprolol (e.g. -16 vs -7
      g/m2, i.e. -13 vs -6%, at 12 months, p < 0.01). MI decreased by 6% with captopril
      (p = 0.05) and by 23% with metoprolol (p < 0.01), with no difference between the
      groups. Changes in LVMI were not related to changes in MI in the two groups, or
      when all patients were analyzed together. High-density lipoprotein (HDL)
      cholesterol decreased (p < 0.05) by both drugs, with small effects on low-density
      lipoprotein (LDL), and triglycerides increased by 30% with metoprolol (p < 0.01).
      CONCLUSION: Blockade of the renin-angiotensin-aldosterone system has a role
      beyond that of blood pressure reduction in the regression of LV mass. There was
      no relationship between regression of LV mass and improvement in insulin
      sensitivity. We could not confirm a beneficial effect of ACE inhibition on
      insulin sensitivity. Thus, our results do not support the importance of insulin
      in the control of LV geometry.

PMID- 11467760
TI  - Less adrenergic response to mental task during verapamil compared to amlodipine
      treatment in hypertensive subjects.
AB  - We compared the effects of amlodipine and verapamil slow release on autonomic
      responses to a 5-min mental arithmetic test (MST) in patients with mild to
      moderate hypertension. Twenty subjects received 8 weeks of verapamil slow release
      240 mg or amlodipine 10 mg in a double-blind crossover design, both after 4
      weeks' placebo. Heart rate (HR) and blood pressure (BP) were continuously
      monitored. Venous plasma catecholamines were analysed by a radioenzymatic assay.
      Baroreflex sensitivity (BRS) was estimated with the transfer function technique.
      Calculations of the area under the curve (AUC) were used to estimate average HR,
      BP and catecholamine concentrations. The reactivity to MST was estimated as
      percent change from the basal AUC. A paired t-test was performed. Data are means
      +/-SEM. Compared to verapamil, amlodipine increased average noradrenaline (NA)
      concentrations (245 +/- 23 vs 191 +/- 17 pg/l, respectively, p = 0.005), NA
      reactivity (14.0 +/- 5.5% vs -2.9 +/- 3.3, p = 0.004), average HR (65 +/- 2 vs 61
      +/- 2 beats/min, p < 0.001) and HR reactivity (2.5 +/- 1.0 vs 0.1 +/- 0.9%, p =
      0.056). BP did not differ significantly. BRS correlated with average and baseline
      HR on both medications (r = -0.53 and -0.63, p < or = 0.03). We conclude that
      adrenergic responses to MST are blunted on treatment with verapamil compared to
      amlodipine in hypertensive patients.

PMID- 11467761
TI  - The Captopril Prevention Project, further analyses on left ventricular
      hypertrophy and diabetes.

PMID- 11467762
TI  - Treatment strategy to control blood pressure optimally in hypertensive patients.
AB  - Pharmacological treatment of hypertension significantly reduces the incidence of
      cardiovascular diseases. Unfortunately, only a fraction of hypertensive patients
      benefit maximally from the protection afforded by the blood pressure lowering,
      mainly because the blood pressure control achieved during antihypertensive
      therapy remains often insufficient. One way to improve this situation is to
      individualize the treatment in determining for each patient the most simple drug
      regimen, which is at the same time efficacious and well tolerated. To this end,
      combining small doses of drugs acting by different mechanisms is often required.
      It is also essential that physicians develop skills to motivate their patients to
      comply lifelong with the treatment.

PMID- 11467763
TI  - Echocardiographic left ventricular geometry in hypertensive patients with
      electrocardiographic left ventricular hypertrophy: The LIFE Study.
AB  - AIM: To assess the prevalence of echocardiographic left ventricular hypertrophy
      (LVH) and concentric remodeling in hypertensive patients with
      electrocardiographic (ECG)-LVH and to estimate the cost-effectiveness of
      echocardiography and ECG for detection of LVH. DESIGN: Echocardiographic LV
      measurements and the prevalence of abnormal LV geometric patterns were compared
      between 964 hypertensive patients with ECG-LVH (Cornell voltage-duration product
      > 2440 and/or SV1 +/- RV5-6 > 38 mm) participating in the LIFE trial and groups
      of 282 employed hypertensives and 366 apparently normal adults. RESULTS: Among
      both women and men, stepwise increases from reference subjects to employed
      hypertensives to LIFE patients were observed for LV wall thicknesses, chamber
      size and mass. Mean LV mass/body surface area (BSA) and LV mass/height(2.7) were
      substantially larger in LIFE patients than normal adults among women (113 vs 69
      g/m2 and 55 vs 32 g/m(2.7), p <0.001) and men (127 vs 83 g/m2 and 55 vs 36
      g/m(2.7), p < 0.001), with intermediate values in employed hypertensives.
      Compared to the latter group, LIFE patients had higher prevalences of concentric
      LVH (25-29% vs 3-4%) and eccentric LVH (45-51% vs 13-17%) but not concentric LV
      remodeling (8-11% vs 12-14%). LVH was present in 70% of LIFE patients by LV
      mass/BSA criteria and 76% by LV mass/height(2.7) criteria (odds ratios = 11.4 and
      13.5 vs employed hypertensives). CONCLUSIONS: The ECG criteria used in LIFE
      identify hypertensive patients with a >70% prevalence of anatomic LVH, allowing
      accurate identification of high-risk status by this commonly used technique.

PMID- 11467764
TI  - Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE
      trial. The Valsartan Antihypertensive Long-term Use Evaluation.
AB  - Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1)
      receptor developed for the treatment of hypertension. The Valsartan
      Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events
      in Hypertension is a double-blind, randomized prospective, parallel group study
      designed to compare the effects of valsartan with those of the calcium-antagonist
      amlodipine on the reduction of cardiac morbidity and mortality. Patients with
      essential hypertension, aged 50 years and older, and at particularly high risk of
      coronary events were enrolled. 18,119 patients were screened and 15,314 patients
      in 31 countries were randomized mainly between January 1998 and December 1999.
      These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of
      their randomization to blinded medication. The population comprises both genders
      (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6
      kg/m2, coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes
      mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized
      participants had been treated for high blood pressure for at least 6 months when
      screened for the study. The randomized population is now being treated (goal
      blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450
      patients experience primary cardiac endpoint defined as clinically evident or
      aborted myocardial infarction, hospitalization for heart failure or death caused
      by coronary heart disease.

PMID- 11467765
TI  - Polymorphisms in candidate genes for blood pressure regulation in young men with
      normal or elevated screening blood pressure.
AB  - We have previously shown correlations between cardiovascular risk factors such as
      blood pressure (BP), sympathetic nervous system activity, lipids and insulin
      resistance in young men with elevated screening BP. In the present study we aimed
      to: (1) compare the genotype distribution and allele frequencies of 11
      polymorphisms in seven candidate genes for BP regulation in healthy 21-year-old
      Caucasian men, between 18 men with normal and 67 men with high screening BP, and
      (2) evaluate the effect of these polymorphisms in candidate genes on casual BP,
      BP responses to mental stress or catecholamines and metabolic parameters
      including insulin sensitivity. There were no differences in genotype
      distributions or allele frequencies between the subjects with normal and those
      with high screening BP. Insulin sensitivity was significantly higher in GG
      homozygotes in the G-261A polymorphism at the alpha 2A-adrenergic receptor
      (alpha(2A)AR) locus compared to GA heterozygotes (p = 0.007). Subjects who were
      homozygous both GG in the G-261A polymorphism at the alpha(2A)AR locus and GlyGly
      in the Arg16Gly polymorphism at the beta2-adrenergic (beta2AR) receptor loci had
      significantly higher insulin sensitivity and lower catecholamine levels during
      mental stress than subjects with other genotypes. Subjects who were II homozygous
      at the angiotensin converting enzyme (ACE) locus and AA homozygous at the
      angiotensin type I receptor (AT1R) locus had lower BP and a better lipid profile
      than the rest of the group. Thus, in this explorative study, we report an
      association between insulin sensitivity and a polymorphism at the alpha(2A)AR
      locus. We suggest the presence of gene-gene interactions in the renin-angiotensin
      system and the sympathetic nervous system.

PMID- 11467766
TI  - Immunological circumvention of multiple organ metastases of multidrug resistant
      human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2
      antibody KM966.
AB  - serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3
      cells. Pretreatment of human effector cells with various cytokines induced
      further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells.
      Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell
      depleted severe combined immunodeficient (SCID) mice developed metastases in
      multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells
      produced metastases more rapidly than SBC-3 cells, suggesting more aggressive
      phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic
      treatment with KM966, given on days 2 and 7, drastically inhibited the formation
      of multiple-organ metastases produced by both SBC-3 and SBC-3/DOX cells,
      indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR
      phenotype. These findings suggest that the mouse-human chimeric KM966 targets the
      GM2 antigen, and might be useful for the immunological circumvention of multiple
      organ metastases of refractory SCLC.

PMID- 11467767
TI  - Different levels of TGFbeta, IL-10, IFNgamma and gelatinase A occur in
      experimental white and black metastases induced by bryostatin 1 or by phorbol
      ester-treated BL6T murine melanoma cells.
AB  - Bryostatin 1 and phorbol esters reduce the intracellular melanin level in high
      metastatic overexpressing nPKCdelta BL6 (BL6T) cells, thereby inducing white
      experimental metastasis in syngeneic mice. We evaluate here the possible
      differences between white and black metastases induced by both treatments on the
      proliferative and metastatic potential as well as on the expression of some
      cytokines involved in the metastatic process such as TGFbeta, IL-10 and IFNgamma.
      The level of expression of gelatinase A is also considered. White and black
      metastases induced after the injection of bryostatin 1- or phorbol ester-treated
      cells into the tail vein of syngenic mice were isolated and analysed for the
      levels of LDH usually used as markers of cytotoxicity, for the levels of
      cytokines and gelatinase A or dissociated and cultured in vitro for a few
      passages. The cultured cells were analysed in vitro for the proliferative
      capacity and the melanin synthesis. The same cells were also re-injected into
      syngeneic mice and the number of experimental metastases were counted after 17
      days or injected with matrigel in order to quantify the proliferative capacity in
      vivo. The results show only one significant difference between bryostatin I and
      phorbol ester, namely the cells obtained from white bryostatin 1-treated cells
      return to a black phenotype after a few passages in culture. This suggests that
      PKC mediates many of the biological effects of bryostatin 1 but that its effect
      is lost in vitro. On the other hand, white and black metastases (at least for
      metastases induced by BL6T cells treated with phorbol ester) do appear
      significantly different. In vivo white metastases show lower levels of LDH, lower
      levels of proliferative capacity into matrigel, higher levels of TGFbeta and
      IFNgamma and, when re-injected into syngeneic mice, give big black metastases.
      Therefore, in murine melanoma cells, the treatment with bryostatin I induces the
      appearance of a white population expressing different levels of TGFbeta,
      IFNgamma, IL-10 and gelatinase A. Such a white population is more difficult to
      diagnose and is capable of turning into a more aggressive phenotype under
      suitable environmental conditions.

PMID- 11467768
TI  - Promotion of colon cancer metastases in rat liver by fish oil diet is not due to
      reduced stroma formation.
AB  - Recently, it was demonstrated that dietary omega-3 polyunsaturated fatty acids
      (PUFAs) induce 10-fold more metastases in number and 1000-fold in volume in an
      animal model of colon cancer metastasis in rat liver. It was observed that tumors
      of rats on a fish oil diet lacked peritumoral stroma unlike tumors in livers of
      rats on a low fat diet or a diet containing omega-6 PUFAs. In the present study,
      only one-third of the tumors in livers of rats on omega-3 PUFA diet contained
      peritumoral stroma, whereas peritumoral stroma was present in 87% of the tumors
      in livers of rats on low fat diet. To explain these findings, we tested the
      hypothesis that fish oil exerts a direct inhibiting effect on the formation of
      extracellular matrix in tumor stroma as a consequence of blocking transformation
      of fat storing cells into myofibroblasts. It was found with immunohistochemical
      analysis of desmin as marker for fat storing cells and alpha-smooth muscle actin
      as marker for myofibroblasts that numbers of myofibroblasts were higher in tumors
      containing intratumoral stroma only than in tumors containing both peritumoral
      and intratumoral stroma. As most of the tumors in fish oil-treated rats contained
      intratumoral stroma only, this suggests that transformation of fat storing cells
      into myofibroblasts was highest in tumor stroma of fish oil-treated rats.
      Therefore, it is unlikely that the lack of stroma around tumors in fish oil
      treated rats is due to inhibition of transformation of fat storing cells into
      myofibroblasts, but lack of peritumoral stroma is rather a consequence of rapid
      development of tumors in livers of fish oil-treated rats.

PMID- 11467769
TI  - Antimetastatic efficacy of adjuvant gemcitabine in a pancreatic cancer orthotopic
      model.
AB  - Gemcitabine is a promising new agent that has been recently studied for
      palliation of advanced (stage IV) unresectable pancreatic cancer. We hypothesized
      that adjuvant gemcitabine would reduce recurrence and metastases following
      surgical resection of pancreatic cancer. To test this hypothesis, we evaluated
      gemcitabine on a green fluorescent protein (GFP) transductant of the human
      pancreatic cancer cell line BxPC-3 (BxPC-3-GFP) using surgical orthotopic
      implantation (SOI) in nude mice. GFP enabled high resolution fluorescent
      visualization of primary and metastatic growth. Five weeks after SOI, the mice
      were randomized into three groups: Group I received exploratory laparotomy only.
      Group II underwent surgical resection of the pancreatic tumor without further
      treatment. Group III underwent tumor resection followed by adjuvant treatment
      with gemcitabine, 100 mg/kg every three days for a total of four doses, starting
      two days after resection. The mice were sacrificed at thirteen weeks following
      implantation and the presence and location of recurrent tumor was recorded.
      Gemcitabine reduced the recurrence rate to 28.6% compared to 70.6% with resection
      only (P = 0.02) and reduced metastatic events 58% in the adjuvant group compared
      to resection only. This study, demonstrating that gemcitabine is effective as
      adjuvant chemotherapy post-pancreatectomy, suggests this new indication of the
      drug clinically.

PMID- 11467770
TI  - Dual X-ray absorptiometry detects disease- and treatment-related alterations of
      bone density in prostate cancer patients.
AB  - Metastatic bone disease is an important clinical problem which has proven
      difficult to study because of a lack of noninvasive investigative modalities.
      Here we show that dual-energy X-ray absorptiometry (DXA) scanning provides
      clinically useful information about the status of metastatic bone lesions in
      cancer patients undergoing palliative treatment. In the study group of 21
      patients, a significant increase in metastatic bone mineral density (BMD) was
      confirmed in prostate (n = 14) relative to breast (n = 7) cancer patients. With
      respect to the prostate cancer cohort, further increases in lesional BMD were
      evident in all evaluable patients in whom biochemical progression occurred;
      conversely, lesional BMD declined in patients who had a partial response to
      therapy. BMD of uninvolved bone decreased with all types of androgen-deprivation
      therapy regardless of whether patients responded or relapsed. We conclude that
      BMD changes in both lesional and uninvolved bone are readily detectable in
      metastatic prostate cancer, and propose that DXA scanning represents a promising
      new approach to monitoring the natural history and therapeutic course of this
      disease.

PMID- 11467771
TI  - Dipeptidyl peptidase IV (DPPIV) inhibits cellular invasion of melanoma cells.
AB  - Dipeptidyl peptidase IV (DPPIV) is a 110-kD, trans-membrane, ectoenzyme, with
      ubiquitous expression. DPPIV has numerous functions including involvement in T
      cell activation, cell adhesion, digestion of proline containing peptides in the
      kidney and intestines, HIV infection and apoptosis, and regulation of
      tumorigenicity in certain melanoma cells. Constitutively expressed on numerous
      epithelial cell types, DPPIV is often disregulated in a variety of human
      malignancies. The most striking evidence of DPPIV down-regulation is found in
      transformed melanocytes. where nearly 100% of melanomas lack DPPIV expression. We
      have identified DPPIV as a gene that can alter the invasive potential of a number
      of melanoma cell lines. By transfecting the full-length cDNA of DPPIV, we have
      established stable melanoma cell lines that express comparable levels of the
      DPPIV protein as normal epidermal melanocytes. Matrigel invasion assays were
      utilized to study the effects of DPPIV expression on the invasive potential of
      these cells. The parental and vector transfectants readily migrated across the
      Matrigel while the invasiveness of DPPIV transfected cells was reduced by greater
      than 75%. The effects on cellular invasion are not attributed to overall growth
      characteristics, as both DPPIV expressing and non-expressing cells behave
      comparably in culture. We have also constructed mutants of DPPIV that lack either
      the extra-cellular serine protease activity or the six amino acid cytoplasmic
      domain. Both mutants were stably expressed in melanoma cells. Matrigel invasion
      assays performed with cells expressing the two mutant forms of the protein
      revealed phenotypic effects similar to wild type function. In this study. we have
      demonstrated that expression of a proteolytically active form of the DPPIV
      protein inhibits the invasiveness of malignant melanoma cell lines lacking
      endogenous DPPIV expression. Furthermore, we have shown that neither the protease
      activity nor the cytoplasmic domain of DPPIV is required for its anti-invasive
      activity.

PMID- 11467772
TI  - The role of matrilysin (MMP-7) in leukaemia cell invasion.
AB  - The matrix metalloproteinases (MMPs) are important in tumour cell invasion and
      metastasis in many common cancers. However, relatively few studies have
      investigated the role of MMPs and their inhibitors, the tissue inhibitors of
      metalloproteinases (TIMPs), in leukaemia cell invasion. This study examined two
      leukaemia cell lines, K562 and HL-60 and showed that the K562 cell line was four
      times more invasive than the HL-60 cell line. The expression of MMP-2, matrilysin
      (MMP-7), MMP-9. TIMP-1, TIMP-2 and TIMP-3 was analysed. Both cell lines produced
      similar amounts of MMP-2, MMP-9 and TIMP-2. The K562 cells expressed more TIMP-1
      than the HL-60 cells and neither cell line expressed TIMP-3. Interestingly, only
      the K562 cells expressed matrilysin suggesting a potential role for matrilysin in
      leukaemia cell invasion. in vitro invasion assays performed in the presence of a
      matrilysin blocking antibody showed a 40% reduction in invasive ability. This
      data suggests that matrilysin plays an important role in leukaemia cell invasion.

PMID- 11467773
TI  - Differences in association of the serine/threonine protein phosphatase PP-2A with
      microtubules of metastatic and nonmetastatic tumor cells.
AB  - Motility and adhesiveness are regulated by a multitude of factors, including
      cytoskeletal polymerization and phosphorylation of cytoskeletal and associated
      proteins. The metastatic Lewis lung carcinoma variant, LLC-LN7, was highly motile
      in vitro and had lower levels of the serine/threonine protein phosphatase PP-2A
      than did the nonmetastatic variant, LLC-C8. Reducing PP-2A activity of the
      nonmetastatic cells pharmacologically or with catalytic (Calpha) subunit
      antisense increased their in vitro motility. Nonmetastatic LLC-C8 cells had a
      greater proportion of polymerized tubulin which co-purified with PP-2A as
      compared to the metastatic LLC-LN7 cells. The PP-2A that was associated with the
      microtubules of these cells showed similar ratios of the Aalpha structural
      subunit to the Calpha/beta catalytic subunits. In contrast, the proportion of the
      regulatory subunit B56alpha was lower in the nonmetastatic LLC-C8 cells as
      compared to the metastatic LLC-LN7 cells. These studies show the role of PP-2A in
      restricting the motility of nonmetastatic tumor cells and suggest that the loss
      of this regulatory control in metastatic LLC-LN7 cells may be due to both a
      reduction in microtubule-associated PP-2A and a difference in the composition of
      the subunits of PP-2A that is associated with the microtubules.

PMID- 11467774
TI  - Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells
      through inducing apoptosis via decreasing Bcl-2 expression.
AB  - Quercetin has been known to have anti-tumor and anti-oxidation activities. In the
      present study, we have investigated its in vitro anti-metastatic activity.
      Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in
      a dose-dependent manner but did not affect their adhesion to either laminin,
      fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the
      proliferation of B16-BL6 cells only in the case of time incubation longer than 48
      h. Quercetin dose-dependently decreased the cell rates in S and G2-M phases of
      cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6
      cells was also demonstrated by flow cytometric assay as well as DNA fragmentation
      with a typical 180-bp ladder band in agarose electrophoresis and a quantitative
      analysis. Furthermore, quercetin markedly inhibited the expression of anti
      apoptotic protein Bcl-2 but hardly influenced Bcl-XL. These results suggest that
      the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are
      closely associated with the arrest of cell cycle as well as the induction of
      apoptosis by decreasing the Bcl-2 expression.

PMID- 11467775
TI  - Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and
      the PI3K-Akt pathways in ovarian cancer cells.
AB  - Cell adhesion to the extracellular matrix appears to trigger a cascade of
      intracellular signalings. We have previously shown that treatment of ovarian
      cancer cells, NOM1, with fibronectin (FN) stimulated matrix metalloproteinase
      (MMP)-9 secretion and thereby activated the invasiveness of cells via the FAK/Ras
      signaling pathway. By use of chemical inhibitors, we investigated the downstream
      effectors critical for FN-dependent secretion of MMP-9. Treatment of cells with
      MEK1 inhibitors, U0126 and PD98059, dramatically suppressed the secretion of MMP
      9 activated by FN. Similarly, P1-3 kinase inhibitors, Wortmannin and LY294002,
      strongly suppressed the FN-dependent secretion of MMP-9 together with the
      inhibition of Akt activation. In contrast, a specific PKC inhibitor (GF109203X)
      showed no inhibitory effect on the FN-dependent MMP-9 secretion. Moreover, we
      found that both the MEK1 inhibitor and the P13-K inhibitor, but not the PKC
      inhibitor, strongly suppressed the invasiveness of NOM1 cells. Taken together,
      our results suggest that activation of dual signaling pathways, MEKI-MAPK and
      P13K-Akt, is required for the FN-dependent activation of MMP-9 secretion. Our
      results suggest the importance of these signaling molecules as a chemotherapeutic
      target for cancer.

PMID- 11467776
TI  - Dietary 4-HPR suppresses the development of bone metastasis in vivo in a mouse
      model of prostate cancer progression.
AB  - The effects of the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) on
      prostate cancer metastasis in vivo were evaluated in the mouse prostate
      reconstitution (MPR) model. MPRs were produced by infection of either
      heterozygous (+/-) or nullizygous (-/-) p53-mutant fetal prostatic epithelial
      cells with the recombinant retrovirus Zipras/myc 9. Previous studies have
      documented that loss of p53 function potentiates metastasis in this model system.
      MPRs were grafted into homozygous (+/+) p53 male mice, fed a 4-HPR containing
      diet or a control diet and maintained until the status of tumor progression
      dictated sacrifice. Under these experimental conditions, treatment with 4-HPR did
      not have a significant effect on primary tumor wet weight for either p53 +/- or
      p53 -/- MPRs. For, p53 +/- MPRs the animals fed the 4-HPR diet had a slight
      improvement in survival and a significant reduction in the number of mesenteric
      metastases (P = 0.0477, t-test). Notably, in p53 +/- MPRs the incidence of
      metastasis to lumbar spine and sternum was 92% in the control animals compared to
      54% in the 4-HPR treated animals (P = 0.035, chi2-test). In p53 -/- MPRs there
      was a trend toward a reduction in the number of soft tissue metastases to lung
      and liver in the 4-HPR group relative to the control diet group and a
      statistically significant reduction in the incidence of metastasis to bone was
      demonstrated in that 50% of control animals versus 30% of 4-HPR treated p53 -/-
      animals harbored bone metastases (P = 0 < 0.05, chi2-test). Cell lines were
      established from portions of the primary tumor and from selected metastatic
      deposits in each experimental group. Clonal analysis, by retroviral integration
      pattern, indicated increased clonal diversity in both the primary tumors and
      metastasis-derived cell lines from 4-HPR treated animals relative to the control
      animals. In vitro treatment with 4-HPR did not reveal discriminating differences
      between cell lines derived from primary tumors and bone metastases or control and
      treatment groups in regard to growth arrest or apoptotic responses. Overall these
      studies indicate limited anti-tumor and anti-metastatic activity in this highly
      aggressive in vivo mouse model of prostate cancer, yet 4-HPR treatment
      significantly suppressed the development of bone metastases in p53 +/- and p53 -/
      MPRs revealing a novel and potentially clinically useful activity of this
      retinoid.

PMID- 11467777
TI  - The effect of parasite dose on disease severity in the rodent malaria Plasmodium
      chabaudi.
AB  - Experiments were designed to look at the relationship between infective dose and
      disease severity using 2 clones of Plasmodium chabaudi that differ in virulence.
      We asked whether there were dose-severity relationships, whether clone
      differences in virulence were maintained over a range of doses, and whether
      disease severity could be accounted for by parasite dynamics. Groups of mice were
      infected with parasite doses differing by an order of magnitude, ranging from 100
      to 1 x 10(8) parasites. Infective dose affected the probability of death, but
      only with the more virulent clone. Dose also affected morbidity. For both clones,
      higher doses induced greater anaemia. Larger doses caused greater weight loss,
      but only for infections with the more virulent clone. Here, for a given dose,
      mice lost a fixed amount of weight, irrespective of their initial weight. Larger
      doses induced earlier mortality and morbidity than did lower dose treatments.
      Finally, dose affected parasite dynamics, with earlier and higher peak parasite
      densities in larger dose infections. All these effects were small relative to
      clone differences in disease severity, which were apparent across the range of
      doses. Dose effects were manifested through the timing and/or magnitude of peak
      parasite densities, broadly supporting the idea that dose affects disease
      severity by altering the time the host has to control parasite densities and
      ameliorate the effects of parasites. We discuss the possible efficacy of
      intervention strategies aimed at reducing human disease severity by reducing
      infective parasite dose.

PMID- 11467778
TI  - Effect of benzimidazole under-dosing on the resistant allele frequency in
      Teladorsagia circumcincta (Nematoda).
AB  - This experiment was designed to determine the effects of under-dosing on the
      frequency of benzimidazole resistant allele in the nematode Teladorsagia
      circumcincta. Fenbendazole (FBZ) was tested at 1/32, 1/16, 1/8 and 1/4 of the
      recommended dose for sheep (5 mg/kg body weight). The fraction of the susceptible
      homozygote (SS), susceptible heterozygote (RS) and resistant homozygote (RR)
      genotypes were compared among FBZ dose groups to evaluate differences between SS
      and RS genotype selective advantage. Almost all SS genotype worms were eliminated
      by 1/4 of the FBZ recommended dose, whereas a significant fraction of the RS
      genotype worms survived treatment. The selective advantage was 4.5 times higher
      for the RS genotype. This selective advantage was determined at 1/4 of the
      manufacturer's recommended dose of FBZ. This value should be taken as an indictor
      of the selective advantage of RS over the SS genotype when lambs are under-dosed.
      A computer simulation was used to study the putative spread of anthelmintic
      resistance over a range of RS selective advantages (2, 4.5 and 10-fold), with two
      average sizes of individual host worm population (20 or 2000 worms/host) and two
      initial R allele frequencies (0.1%, or 1%). In all situations, the lowest
      selective advantage of the RS genotype over the SS genotype was sufficient to
      promote the spread of resistance in susceptible populations. When the RS genotype
      had no selective advantage over the SS genotype, genetic drift almost always led
      to the loss of the R allele, except in the largest populations (average size =
      2000 worms).

PMID- 11467779
TI  - Genetic and biological diversity among isolates of Neospora caninum.
AB  - Neospora caninum is a protozoan parasite that causes bovine abortion. The
      epidemiology of N. caninum is poorly understood and little is known about the
      genetic diversity of the parasite, or whether individual isolates differ in
      virulence. Such diversity may, among other factors, underlie the range of
      pathologies seen in cattle. In this study we analysed biological and genetic
      variation in 6 isolates of N. caninum originating from canine and bovine hosts by
      measurement of growth rate in vitro, Western blotting and random amplification of
      polymorphic DNA (RAPD). This comparative analysis of intra-species diversity
      demonstrated that heterogeneity exists within the species. The relative growth
      rate in vitro, as assessed by 3[H]uracil uptake, showed significant variation
      between isolates. However, no significant differences were detected between the
      antigenic profiles of each isolate by Western blotting. RAPD-PCR was performed on
      DNA from the 6 Neospora isolates; 3 strains of Toxoplasma gondii, Sarcocystis sp.
      and Cryptosporidium parvum were also analysed. Twenty-six RAPD primers gave rise
      to 434 markers of which 222 were conserved between all the Neospora isolates and
      distinguished them from the other Apicomplexa. An additional 54 markers were
      unique for Neospora but were polymorphic within the species and able to
      differentiate between the individual isolates. The RAPD data were subjected to
      pair-wise similarity and cluster analysis and showed that the Neospora isolates
      clustered together as a group, with T. gondii as their nearest neighbour. N.
      caninum isolates showed no clustering with respect either to host or geographical
      origin. The genetic similarity between Neospora isolates from cattle and dogs
      suggests that these hosts may be epidemiologically related, although further
      analysis of bovine and canine field samples are required. The genetic and
      biological diversity observed in this study may have important implications for
      our understanding of the pathology and epidemiology of neosporosis.

PMID- 11467780
TI  - Interferon-gamma-induced apoptosis in host cells infected with Neospora caninum.
AB  - Interferon-gamma (IFN-gamma) has a crucial role for host defence against parasite
      infection. It is not clear, however, how IFN-gamma affects the parasite-infected
      host cells. The effect of IFN-gamma on Neospora caninum-infected cells was
      investigated in murine fibroblasts and canine kidney cells in vitro. In the
      presence of IFN-gamma, the viability of the infected host cell was decreased and
      apoptotic cell death occurred, as analysed by DNA stainings with propidium iodide
      and a terminal deoxy-nucleotidyltransferase-mediated dUTP-biotin nick end
      labelling (TUNEL) and DNA fragmentation. The percentage of apoptotic cells
      depended on the dose of IFN-gamma. Flow cytometric analysis indicated a
      significant increase of FasL expression on the IFN-gamma treated cells following
      N. caninum infection. Moreover, IFN-gamma treatment down-regulated Bcl-2
      expression in the cells cultured with N. caninum while parasite infection up
      regulated Bcl-2 expression. The present study suggests that the IFN-gamma induced
      increases of FasL expression and down-regulated Bcl-2 expression in N. caninum
      infected cells are associated with apoptosis in vitro.

PMID- 11467781
TI  - Isolation and characterization of the Golgi complex of the protozoan Trypanosoma
      cruzi.
AB  - In this study the Golgi complex of the epimastigote forms of Trypanosoma cruzi
      were isolated and characterized. Using well-controlled sonication to rupture the
      cells and centrifugation on a discontinuous sucrose density gradient, a highly
      enriched Golgi fraction was obtained. The Golgi fraction contained most of the
      beta-galactosyltransferase (beta-Gal transferase) and UDP-N-acetyl-glucosamine:
      polypeptide-alpha-N-acetyl-glucosaminyltransferase (O-alpha-GlcNAc transferase)
      activities with minimal contamination of other organelles, as observed by
      enzymatic assays and electron microscopy analysis. To characterize the Golgi from
      T. cruzi cells further, it was incubated with a monoclonal antibody against a 58
      kDa protein involved in the association of the Golgi complex with microtubules in
      mammalian cells. Immunofluorescence microscopy showed that the 58 kDa protein is
      localized in the T. cruzi Golgi region, a result confirmed by high resolution
      scanning electron microscopy immunocytochemistry. Thus, our results show, for the
      first time, that the beta-Gal transferase, the O-alpha-GlcNAc transferase and the
      58 kDa protein are present in the Golgi complex of T. cruzi and are novel
      biochemical markers which can be used in the characterization of this organelle
      in T. cruzi.

PMID- 11467782
TI  - Metronidazole-resistant strains of Trichomonas vaginalis display increased
      susceptibility to oxygen.
AB  - Susceptibility to oxygen and properties relative to oxygen metabolism were
      compared in metronidazole-resistant and susceptible strains of Trichomonas
      vaginalis. The study involved clinical isolates displaying the aerobic type of
      resistance, as well as resistant strains developed in vitro, both with aerobic
      (MR-3) and anaerobic (MR-5, MR-100) resistance. Elevated sensitivity to oxygen of
      the resistant clinical isolates was observed. Progressive increase of
      susceptibility to oxygen also accompanied in vitro development of resistance. No
      correlation was found between the activity of NADH oxidase and aerobic
      resistance, while the in vitro derivative with fully developed anaerobic
      resistance (MR-100) showed about 50% decrease of NADH oxidase activity. The
      superoxide dismutase (SOD) activity was elevated in both resistant clinical
      isolates and in in vitro-developed resistant strains. The changes in levels of
      ferredoxin were insufficient to support ferredoxin deficiency as a cause of
      aerobic metronidazole resistance. Western blot analysis and electron paramagnetic
      resonance spectroscopy of purified hydrogenosomes showed that ferredoxin is
      expressed in aerobically resistant strains and has intact iron-sulfur clusters.
      Down-regulation of ferredoxin was demonstrated only in the late phase of
      development of the anaerobic resistance (MR-100). The results support a link
      between aerobic resistance and defective oxygen scavenging. The increased levels
      of intracellular oxygen, beneficial to resistant parasites when they interact
      with the drug, may have adverse effects on their fitness as shown by their
      increased sensitivity to oxidative stress.

PMID- 11467783
TI  - Histone-like proteins from fish are lethal to the parasitic dinoflagellate
      Amyloodinium ocellatum.
AB  - Antimicrobial proteins were purified from acid extracts of rainbow trout
      (Oncorhynchus mykiss) and sunshine bass (Morone saxatilis male x M. chrysops
      female) skin, gill and spleen by reverse-phase HPLC. Mass spectrometry and amino
      acid sequence data suggest that these proteins are closely related to histone H2B
      and histone H1 and thus they were designated histone-like proteins (HLPs). These
      proteins were lethal to Amyloodinium ocellatum, which is one of the most
      important parasitic agents affecting fish. Antibiotic concentrations as low as
      12.5 microg/ml were inhibitory. Activity was directed against the trophont
      (feeding) stage of the parasite, while the disseminative (dinospore) stage was
      unaffected. Thus, HLPs act unlike typical drugs used to treat amyloodiniosis,
      which usually target the dinospore. Both the ability of the parasite to infect
      host cells, as well as the ability to grow and differentiate after infection were
      severely inhibited. This is in contrast to magainin 2, which was similarly toxic
      to both the dinospore and trophont stages. These findings provide further
      evidence that histone-like proteins may be important defensive molecules in fish.

PMID- 11467784
TI  - Investigations of intermediate host specificity help to elucidate the taxonomic
      status of Trichobilharzia ocellata (Digenea: Schistosomatidae).
AB  - The avian schistosomatid Trichobilharzia ocellata plays an important role as
      causative agent of cercarial dermatitis of humans in Europe. In order to improve
      the taxonomic knowledge on this parasite, studies of miracidial chemo-orientation
      as well as experimental infections of different snail species were conducted
      using strains of T. ocellata and T. franki. Both schistosomes exhibited a high
      intermediate host specificity. The miracidia clearly preferred the SCW (snail
      conditioned water) of the respective natural intermediate host to SCW of other
      sympatric snail species. T. ocellata proved to be capable of infecting Lymnaea
      stagnalis and Stagnicola palustris, but could not develop in Radix ovata or R.
      auricularia. T. franki established an infection in specimens of R. auricularia
      and R. ovata, but not in L. stagnalis or S. palustris. The results imply that the
      intermediate host spectrum of T. ocellata is limited to L. stagnalis and S.
      palustris. Findings of T. ocellata (or Cercaria ocellata) that originated from
      snails of the genus Radix are likely to have actually belonged to species such as
      T. franki or T. regenti. The assumption that T. szidati is synonymous to T.
      ocellata is also discussed.

PMID- 11467785
TI  - The relationship between parasitological status and humoral responses to Loa loa
      antigens in the Mandrillus sphinx model after immunization with irradiated L3 and
      infection with normal L3.
AB  - In order to identify antigens associated with protection and those associated
      with active infection, the humoral immune response of 6 Mandrillus sphinx
      immunized with 150 irradiated L3 and challenged with 100 normal L3 of Loa loa or
      6 animals infected with 100 L3 were compared. The plasma of these animals was
      analysed by Western blot using adult, Mf and L3 antigens. Several antigens with
      molecular weights varying from 120 kDa to 13 kDa were recognized by the plasma of
      all animals. It was shown that early recognition of microfilarial antigens with
      molecular weights of 97, 68, 45 and 33 kDa correlated with the amicrofilaraemic
      state. A total of 83% of animals with circulating microfilariae had antibodies
      against the microfilariae 21 kDa antigen. Furthermore, the antibodies against the
      21 kDa appeared 1 month before detection of microfilariae in the peripheral blood
      of 80% of these animals, and declined when animals became amicrofilaraemic. In
      contrast, when L3 antigen was used, a molecule with a relative molecular weight
      of 20 kDa was recognized by antibodies of the only animal which remained
      amicrofilaraemic for 1 year after immunization with irradiated L3. These results
      suggest that the microfilarial molecule of 21 kDa may be useful as a marker of
      Loa loa patent infection, whereas the 97, 68, 45 and 33 kDa molecules of
      microfilariae and the L3 molecule of 20 kDa may be associated with resistance
      against Loa loa.

PMID- 11467786
TI  - Molecular cloning and characterization of a serine proteinase inhibitor from
      Trichinella spiralis.
AB  - We produced a recombinant protein from a cDNA library from muscle larvae of
      Trichinella spiralis which had proteinase inhibitory activity. The predicted
      amino acid sequence of the clone had an identity of only 30% to the serine
      proteinase inhibitors (serpins) from Caenorhabditis elegans or Brugia malayi. At
      the putative reactive region, however, the identity was about 50%. The
      recombinant protein expressed in Escherichia coli inhibited 82% of the activity
      of the serine proteinase (trypsin). Stage-specific expression of this protein was
      suggested from the following experiments. Antibody against the recombinant
      protein could stain proteins migrating at about 42 kDa (which is the expected
      size from the sequence) in crude extracts from newborn larvae and 18-day post
      infection (p.i.) muscle larvae, but it failed to stain any proteins in crude
      extracts from 30-day p.i. muscle larvae. Production of mRNA transcript for the
      serpin gene was restricted largely to the newborn larvae and to 18-day p.i.
      muscle larvae. The antibody reacted with the stichocytes of the larvae at 18 days
      p.i., but did not react with the muscle larvae at 24 days and 30 days p.i.

PMID- 11467787
TI  - Different response of satellite cells in the kinetics of myogenic regulatory
      factors and ultrastructural pathology after Trichinella spiralis and T.
      pseudospiralis infection.
AB  - Infection of an intracellular parasitic nematode, Trichinella spiralis, resulted
      in severe damage in muscle cells which was followed by activation and
      proliferation of satellite cells. The repairing process, shortly after the
      damage, histopathologically resembled those seen after mechanical injury.
      Resemblance was also true for kinetics of expression of myogenic regulatory
      factors (MyoD, myogenin and MRF4). The difference resided in the next step where
      the muscle cell infected with T. spiralis transformed to a unique cell which is
      parasitologically known as the nurse cell, and the proliferated satellite cells
      did not differentiate to the muscle cell but to the nurse cell
      (misdifferentiation). Thus the nurse cell was a fusion of the transformed
      infected muscle cell and misdifferentiated satellite cells. Infection with
      another species of Trichinella, T. pseudospiralis, also caused cell damage, but
      more extensively involving the entire length of the infected muscle cells because
      no septum was formed to minimize the affected area. Therefore, a large number of
      satellite cells were activated and proliferated. The myogenic regulatory factors
      such as MyoD and myogenin were activated for a longer period than in the case
      with T. spiralis infection. The infected muscle cell transformed to the nurse
      cell, whose cytoplasm was characterized by extensive smooth endoplasmic
      reticulum. Satellite cells misdifferentiated to the nurse cell, whose cytoplasm
      was amorphous, void of distinct cell organelles. The two kinds of cytoplasm did
      not fuse as examined thus far. Thus infection with T. spiralis and T.
      pseudospiralis caused misdifferentiation of satellite cells, but in a different
      way.

PMID- 11467788
TI  - Acquired immunity to Trichuris suis infection in pigs.
AB  - Strong resistance to reinfection developed in pigs as a result of trickle
      inoculations with Trichuris suis (250 infective eggs twice weekly for 4 weeks).
      At challenge (4000 eggs) 8 weeks after the last trickle inoculation, we observed
      a 96% reduction in the mean number of established challenge worms in immunized
      (TRI/CHA) compared with non-immunized controls (CON/CHA) (74 v. 1753; P = 0.004).
      Moreover, the total faecal egg excretion was significantly lower in immunized
      pigs compared with controls (P = 0.0003). The trickle inoculations depressed pig
      weight gains over the 8-week course of immunization (P = 0.042). It was observed
      that a small number of pigs developed a weaker level of resistance, reflecting
      the importance of genetic determinants. The relevance of these data to the
      population biology of porcine and human whipworm infections is discussed.

PMID- 11467789
TI  - Epidemiological investigation of the central Scotland outbreak of Escherichia
      coli O157 infection, November to December 1996.
AB  - On Friday, 22 November 1996, the microbiologist at a hospital in Lanarkshire,
      Scotland, identified presumptive Escherichia coli O157 in faecal specimens
      submitted by three patients with bloody diarrhoea, and confirmed its presence in
      one. Over the next 6 h, 12 more potential cases were identified. Investigations
      first indicated then confirmed a single food premises as the source of infection.
      Effective control measures were applied promptly. The outbreak was declared over
      on 20 January 1997, by which time 512 cases had been identified, and infection
      with the outbreak strain confirmed in 279. Twenty deaths occurred in cases during
      the outbreak and there were two more in cases during 1997. Seventeen of these
      deaths resulted from the outbreak. This paper describes the outbreak's
      epidemiological investigation, referring to other investigations, and control
      measures, where appropriate.

PMID- 11467790
TI  - Molecular epidemiology of endemic Clostridium difficile infection.
AB  - This is the first study to provide a comprehensive insight into the molecular
      epidemiology of endemic Clostridium difficile and particularly that associated
      with a recently recognized epidemic strain. We DNA fingerprinted all C. difficile
      isolates from the stools of patients with symptomatic antibiotic-associated
      diarrhoea and from repeated samples of the inanimate ward environment on two
      elderly medicine hospital wards over a 22-month period. Notably, C. difficile was
      not recoverable from either ward immediately before opening, but was found on
      both wards within 1-3 weeks of opening, and the level of environmental
      contamination rose markedly during the first 6 months of the study period. C.
      difficile infection (CDI) incidence data correlated significantly with the
      prevalence of environmental C. difficile on ward B (r = 0.76, P < 0.05) but not
      on ward A (r = 0.26, P > 0.05). We found that RAPD and RS-PCR typing had similar
      discriminatory power, although, despite fingerprinting over 200 C. difficile
      isolates, we identified only six distinct types. Only two distinct C. difficile
      strains were identified as causing both patient infection and ward contamination.
      Attempts to determine whether infected patients or contaminated environments are
      the prime source for cross-infection by C. difficile had limited success, as over
      90% of C. difficile isolates were the UK epidemic clone. However, a non-epidemic
      strain caused a cluster of six cases of CDI, but was only isolated from the
      environment after the sixth patient became symptomatic. The initial absence of
      this strain from the environment implies patient-to-patient and/or staff-to
      patient spread. In general, routine cleaning with detergent was unsuccessful at
      removing C. difficile from the environment. Understanding the epidemiology and
      virulence of prevalent strains is important if CDI is to be successfully
      controlled.

PMID- 11467791
TI  - Methicillin-resistant Staphylococcus aureus (MRSA): a community-based prevalence
      survey.
AB  - A prevalence survey of nasal methicillin-resistant Staphylococcus aureus (MRSA)
      carriage was undertaken on a random sample of adults (aged over 16) resident in
      the community in Birmingham, UK during 1998. Microbiological samples were taken
      from the anterior nares at the subjects' general practice or in their home.
      Information about risk factors for the acquisition of MRSA was obtained via a
      self-completed questionnaire. A 58% response rate (280/483) was achieved. The
      prevalence of nasal MRSA colonization was 1.5% [4/274, 95% confidence interval
      (CI) 0.03-2.9%]. Twenty-three per cent (63/274) of subjects were nasal carriers
      of S. aureus. Six per cent (4/63) of S. aureus isolates were MRSA and 2 of the 4
      MRSA carriers reported previous contact with health facilities. The prevalence of
      MRSA colonization in the general adult population in Birmingham appears to be
      low.

PMID- 11467792
TI  - Detection and typing of vancomycin-resistance genes of enterococci from clinical
      and nosocomial surveillance specimens by multiplex PCR.
AB  - Ninety-three clinical isolates of vancomycin-resistant enterococci (VRE)
      collected from nine hospitals in Taiwan were examined for the presence of vanA,
      vanB, vanC1, or vanC2/vanC3 genes by a multiplex PCR. Forty-seven of these VRE
      isolates were vanA positive, 1 contained both vanC1 and vanA, 40 harboured vanB,
      2 were vanC1, and 3 were identified to be vanC2/vanC3. Twenty-four vanA isolates
      were sensitive to teicoplanin and thus did not have a typical VanA phenotype.
      Five isolates with the VanC phenotype harboured vanB. None of the 40 clinically
      isolated vancomycin-susceptible E. faecium or E. faecalis and the vancomycin
      resistant Leuconostoc and Pediococcus isolates were positive for any of the van
      genes. While performing nosocomial surveillance, VRE were isolated from 47 of 467
      rectal swabs by culture. Compared with the conventional culture method, the
      sensitivity and specificity of the multiplex PCR for detecting and identifying
      vancomycin-resistance genes in enterococci directly from culture-positive broth
      were 97.9% and 100%, respectively. The results suggest that genotypic
      characterization of vancomycin-resistance is necessary for all clinical VRE
      isolates and that the multiplex PCR assay can be an alternative method for this
      purpose.

PMID- 11467793
TI  - Acute poststreptococcal glomerulonephritis: public health implications of recent
      clusters in New South Wales and epidemiology of hospital admissions.
AB  - Acute poststreptococcal glomerulonephritis (APSGN) is an inflammatory kidney
      condition that can complicate Group A streptococcal infections. Two clusters of
      APSGN occurred recently in New South Wales (NSW), Australia; one in a rural town
      in December 1999 and the other in a Sydney suburb in January 2000. We interviewed
      carers of the affected children but found no common exposures except three of the
      Sydney cases were cousins in frequent contact. To assess the probability of these
      clusters occurring, we analysed hospital admissions for acute glomerulonephritis,
      as a proxy for APSGN in younger patients. The incidence of acute
      glomerulonephritis in NSW during 1989/90-1997/8 in residents aged under 20 years
      was 2.2/100000/year (95% CI 2.0-2.5). Incidence was highest in children aged 5-9
      years, boys and Aboriginal children. We found no evidence for other clusters
      during that period. The recent clusters highlight the continued potential for
      unexpected future outbreaks of APSGN.

PMID- 11467794
TI  - A large outbreak of conjunctivitis caused by a single genotype of Neisseria
      gonorrhoeae distinct from those causing genital tract infections.
AB  - Several epidemics of gonococcal conjunctivitis have occurred in Aboriginal
      populations in Central Australia. In 1997, the first outbreak in the Kimberley
      region of Western Australia occurred, spreading to Central Australia with a total
      of 447 cases. A genotyping method was applied directly to DNA extracted from
      patient samples to characterize the gonococcus causing the epidemic and to
      compare it with contemporaneous genital isolates. Those positive conjunctival
      specimens from Kimberley and Central Australia that could be genotyped were all
      indistinguishable, but were distinct from the genital gonococci, even when they
      shared the same auxotype and serotype. This suggested that the outbreak was due
      to a single genotype of Neisseria gonorrhoeae that had probably been carried
      between communities by infected individuals. We did not find evidence to support
      the existence of a genital reservoir of the types causing epidemic gonococcal
      conjunctivitis.

PMID- 11467795
TI  - Environmental mycobacteria in northern Malawi: implications for the epidemiology
      of tuberculosis and leprosy.
AB  - More than 36000 individuals living in rural Malawi were skin tested with antigens
      derived from 12 different species of environmental mycobacteria. Most were
      simultaneously tested with RT23 tuberculin, and all were followed up for both
      tuberculosis and leprosy incidence. Skin test results indicated widespread
      sensitivity to the environmental antigens, in particular to Mycobacterium
      scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with
      evidence of exposure to 'fast growers' (i.e. with induration to antigens from
      fast growers which exceeded their sensitivity to tuberculin), but not those
      exposed to 'slow growers', were at reduced risk of contracting both tuberculosis
      and leprosy, compared to individuals whose indurations to the environmental
      antigen were less than that to tuberculin. This evidence for cross protection
      from natural exposure to certain environmental mycobacteria may explain
      geographic distributions of mycobacterial disease and has important implications
      for the mechanisms and measurement of protection by mycobacterial vaccines.

PMID- 11467796
TI  - A statewide outbreak of cryptosporidiosis in New South Wales associated with
      swimming at public pools.
AB  - From December 1997 to April 1998, 1060 laboratory-confirmed cryptosporidiosis
      cases were reported in New South Wales, Australia. In a case-control study,
      compared with 200 controls, the 100 cases were younger (mean age 42 versus 71
      years; P < 0.0001), more likely to report swimming at a public pool (59% versus
      38%; adjusted OR and 95% CI = 27; 1.4-5.1) and swimming in a dam, river or lake
      (OR = 48; 1.1-20.3) but less likely to report drinking bottled water (OR = 0.4;
      0.2-0.9). In subgroup analyses, in rural areas illness was associated mainly with
      contact with another person with diarrhoea, and in urban areas illness was
      associated with swimming in a public pool. Cryptosporidium oocysts were more
      commonly detected in pools to which at least two notified cases had swum (P =
      004). Outbreaks of cryptosporidiosis can be prolonged, involve multiple pools and
      be difficult to control.

PMID- 11467797
TI  - Emerging trends in the epidemiology of invasive mycoses in England and Wales
      (1990-9).
AB  - Invasive fungal infections are becoming an increasing public health problem owing
      to the growth in numbers of susceptible individuals. Despite this, the profile of
      mycoses remains low and there is no surveillance system specific to fungal
      infections currently existing in England and Wales. We analysed laboratory
      reports of deep-seated mycoses made to the Communicable Disease Surveillance
      Centre between 1990 and 1999 from England and Wales. A substantial rise in
      candidosis was seen during this period (6.76-13.70 reports per million
      population/year), particularly in the older age groups. Rates of cryptococcosis
      in males fluctuated over the decade but fell overall (1.05-0.66 per million
      population/year), whereas rates of female cases gradually rose up until 1998
      (0.04-0.41 per million population/year). Reports of Pneumocystis carinii in men
      reduced substantially between 1990 and 1999 (2.77-0.42 per million
      population/year) but showed little change in women. Reports of aspergillosis
      fluctuated up until 1996, after which reports of male and female cases rose
      substantially (from 0.08 for both in 1996 to 1.92 and 1.69 per million
      population/year in 1999 for males and females respectively), largely accounted
      for by changes in reporting practice from one laboratory. Rates of invasive
      mycoses were generally higher in males than females, with overall male-to-female
      rate ratios of 1.32 (95% CI 1.25-1.40) for candidosis, 1.30 (95% CI 1.05-1.60)
      for aspergillosis, 3.99 (95% CI 2.93-5.53) for cryptococcosis and 4.36 (95% CI
      3.47-5.53) for Pneumocystis carinii. The higher male than female rates of reports
      is likely to be a partial reflection of HIV epidemiology in England and Wales,
      although this does not fully explain the ratio in infants and older age groups.
      Lack of information on underlying predisposition prevents further identification
      of risk groups affected. Whilst substantial under-reporting of Pneumocystis
      carinii and Cryptococcus species was apparent, considerable numbers of
      superficial mycoses were misreported indicating a need for clarification of
      reporting guidelines. Efforts to enhance comprehensive laboratory reporting
      should be undertaken to maximize the utility of this approach for surveillance of
      deep-seated fungal infections.

PMID- 11467798
TI  - Comparative utility of restriction fragment length polymorphism analysis and gene
      sequencing to the molecular epidemiological investigation of a viral outbreak.
AB  - Restriction fragment length polymorphism (RFLP) analysis and partial-genome DNA
      sequencing are commonly used to infer genetic relationships among pathogens. This
      study compares the application of both techniques to the analysis of 16
      pseudorabies virus isolates collected during a 1989 outbreak. Genetic distances
      derived from RFLP and DNA sequence data were not significantly correlated with
      geographic distances between farms from which isolates were collected. RFLP-based
      genetic distance was, however, strongly correlated with temporal distance between
      isolates (days separating time of isolation). Sequence-based genetic distance was
      significantly correlated with temporal distance only when synonymous changes
      (nucleotide changes not leading to amino acid changes) were considered
      separately. Conversely, non-synonymous changes were correlated with the host
      species of origin of the viral isolate. These results indicate that selectively
      neutral genetic changes most accurately reflect historical relationships, but
      that non-neutral changes most accurately reflect the biological environment of
      the viral isolate (e.g. host immune system).

PMID- 11467799
TI  - Outbreak of Norwalk virus in a Caribbean island resort: application of molecular
      diagnostics to ascertain the vehicle of infection.
AB  - In 1998, an outbreak of gastroenteritis affected at least 448 persons including
      122 staff at a resort hotel in Bermuda. A survey among staff indicated that
      gastroenteritis was associated with eating or drinking at the hotel (OR = 60, 95%
      CI = 2.4-15.1). Multiple specimens of drinking water had elevated faecal coliform
      levels and Escherichia coli present, suggestive of faecal contamination. Stools
      from 18 of the 19 persons with gastroenteritis that were tested were positive for
      genogroup-II Norwalk-like viruses (NLVs). RT-PCR analysis of a 31 specimen of
      water produced a genogroup-II NLV genome with a sequence identical to that of
      NLVs in the stools of three ill persons. This outbreak shows the value of new
      molecular diagnostics to link illness with a contaminated source through the use
      of sequence analysis. The risk of outbreaks such as these could be reduced in
      tourism dependent regions like Bermuda and the Caribbean by regular evaluation of
      data from the inspection and monitoring of drinking water supplies and waste
      water systems, by ensuring the chlorination of supplemental drinking water
      supplies and by establishing food-safety initiatives.

PMID- 11467800
TI  - The seroepidemiology of varicella in Italy.
AB  - We conducted a seroepidemiological study to evaluate the potential impact of mass
      varicella vaccination on the transmission of varicella-zoster virus (VZV) in
      Italy, where vaccination is not mandatory. We tested 3179 serum samples,
      collected from September 1996 to October 1997, for specific anti-VZV antibodies
      using a commercially available ELISA. The results confirmed that varicella
      typically involves children (82.1% seroprevalence among 10- to 14-year-olds) and
      that the mean age of acquiring the infection seems to be increasing. The results
      also revealed that southern Italy, compared to the rest of the country, has a
      greater circulation of VZV and an earlier age of acquisition. The potential
      impact of mass vaccination among 12- to 18-month-old children on the
      epidemiological trend of the infection must be carefully considered, in that
      failure to reach high levels of coverage could lead to an increase in the mean
      age of acquisition, which is already occurring in Italy.

PMID- 11467801
TI  - An outbreak of echovirus 11 in a children's home.
AB  - An outbreak of echovirus 11 infection was observed in a children's home that
      housed 16 children. Nine children younger than 1 year shared a large room on the
      first floor, which contained a large basin. Three of them presented with aseptic
      meningitis with CSF and stool samples positive for echovirus 11. The other six
      infants who shared the room were asymptomatic but their stools were positive for
      echovirus 11. Seven infants aged 1-2 years stayed on the second floor and were
      asymptomatic. One of them had positive stool culture for echovirus 11. No virus
      was isolated from stool samples taken from the 26 staff members. However,
      serology was suggestive for recent echovirus 11 infection in seven asymptomatic
      staff members. All seven worked either exclusively on the first floor or
      alternately on both floors. Our survey demonstrated that echovirus 11 may spread
      very efficiently in children's homes. The rate of meningitis in the infected
      infants was 30% while all the recently infected adults were asymptomatic.

PMID- 11467802
TI  - Genotypic analysis of Staphylococcus aureus from milk of dairy cows with mastitis
      in Argentina.
AB  - Staphylococcus aureus is the most prevalent pathogen causing mastitis of dairy
      ruminants. This study was developed to ascertain the genotypes and genealogical
      relationship among strains isolated from milk of bovines with mastitis in
      Argentina. Molecular epidemiological analysis of S. aureus was performed on 112
      isolates from 21 districts. Clonality was assessed by SmaI pulsed-field gel
      electrophoresis (PFGE) typing, automated EcoRI ribotyping and restriction enzyme
      analysis of plasmid (REAP) DNA profiles. A total of 22 band patterns distributed
      in four clusters were found by SmaI PFGE analysis. The similarity of clusters 2,
      3 and 4 with cluster 1 was 0.73, 0.69 and 0.33, respectively, and 101 of 112
      isolates belonged in cluster 1. PFGE band patterns from 42 isolates within
      cluster I were indistinguishable from each other (type A). The second largest
      group of isolates with indistinguishable PFGE band patterns was subtype A11,
      which was composed of 19 isolates. Automated ribotyping assigned the 112 isolates
      into 13 ribotypes. Among these, the most prevalent ribotypes I and VI were
      composed of 49 and 35 isolates respectively. Although there was certain
      correspondence between PFGE genotypes and ribotypes, further discrimination was
      achieved by combining both methods. REAP DNA profile analysis was useful to
      provide even further discrimination between isolates with identical PFGE genotype
      and ribotype. The most prevalent S. aureus strains A/I and A11/VI were widely
      distributed in the country and were not restricted to individual nearby
      locations. Prevalence of these two strains varied consecutively within a period
      of 8 years. Whether the shift in type prevalence was due to selection of a
      phenotypic trait remains undisclosed.

PMID- 11467803
TI  - Isolation of a non-haemadsorbing, non-cytopathic strain of African swine fever
      virus in Madagascar.
AB  - African swine fever (ASF) suspected clinically in Madagascar (1998-9) was
      confirmed by polymerase chain reaction (PCR) and nucleotide sequencing, following
      virus isolation. No haemadsorption or cytopathic effect could be detected
      following leukocyte inoculation, but viral growth in cells was confirmed by PCR.
      Detection of ASF virus genome was carried out by amplification of a highly
      conserved region coding for the p72 protein. Nucleotide sequencing of the
      amplicon revealed 99.2% nucleotide identity between the recent Malagasy strains
      and a virus recovered from the 1994 outbreak in Mozambique (SPEC265). A
      serological survey performed on 449 sera, revealed that only 5.3% of the sera
      taken from pigs between 1998 and 1999 were positive.

PMID- 11467804
TI  - Effects of mineral salts and calcium chelating agents on the gelation of renneted
      skim milk.
AB  - The effects of adding CaCl2, orthophosphate, citrate, EDTA, or a mixture of
      these, to reconstituted skim milk (90 g of solids/kg solution) on the gelation of
      renneted milk were mediated by changes in Ca2+ activity and the casein micelle.
      At pH 6.65, the addition of citrate or EDTA, which removed more than 33% of the
      original colloidal calcium phosphate with the accompanying release of 20% casein
      from the micelle, completely inhibited gelation. Reformation of the depleted
      colloidal calcium phosphate and casein in the micelle, by the addition of CaCl2,
      removed this inhibition. When the minimum requirements for colloidal calcium
      phosphate and casein in the micelle were met, the coagulation time decreased with
      increasing Ca2+ activity, leveling off at high Ca2+ activity. The storage modulus
      of renneted gels, measured at 3 h, increased with increasing colloidal calcium
      phosphate content of micelles up to a level at which it was approximately 130% of
      the original colloidal calcium phosphate in the micelles. Further increases in
      colloidal calcium phosphate by the addition of CaCl2, orthophosphate, or mixtures
      of these, which did not change the proportion of casein in the micelle, decreased
      the storage modulus. The gelation of the renneted milk was influenced by Ca2+
      activity, the amounts of colloidal calcium phosphate, and casein within the
      micelle, with the effects of colloidal calcium phosphate and casein within the
      micelle clearly dominating the storage modulus. These results are consistent with
      the model of Horne (Int. Dairy J. 8:171-177, 1998) which postulates that,
      following cleavage of the stabilizing K-casein hairs by rennet, the properties of
      the rennet gel are determined by the balance between the electrostatic and
      hydrophobic forces between casein micelles.

PMID- 11467805
TI  - Microencapsulation of beta-galactosidase with fatty acid esters.
AB  - The present study was carried out to find an appropriate coating material to
      microencapsulate lactase and the conditions under which it could be used. As a
      coating material, medium-chain triacylglycerol (MCT) and polyglycerol
      monostearate (PGMS) were superior. Three different percentages of microcapsules
      (2, 4, and 6%) were added and subdivided into three groups by washing time (0, 1,
      and 2). The highest efficiency of microencapsulation was found in the ratio of
      15:1 as coating to core material with both MCT (94.9%) and PGMS (72.8%). Lactose
      content was not significantly changed up to 12 d with MCT and up to 8 d with PGMS
      with 2% of twice washed microcapsule addition. Also, sweetness was not
      significantly increased in storage compared with that of market milk. The present
      study provides evidence that emulsifiers can be used as an effective coating
      material to microencapsulate lactase. In addition, these results suggest that
      acceptable milk products can be prepared with microencapsulated lactase.

PMID- 11467806
TI  - Suppressive effects of bifidobacteria on lipid peroxidation in the colonic mucosa
      of iron-overloaded mice.
AB  - The antioxidative effects of live bifidobacteria on lipid peroxidation in the
      colonic mucosa were investigated. Bifidobacterium bifidum strain Yakult, which
      has been used for production of fermented milk, most effectively inhibited lipid
      peroxidation catalyzed by ferrous iron in liposomes among 10 species of
      bifidobacteria from human intestinal flora. Oral administration of B. bifidum
      strain Yakult for 2 wk significantly decreased the level of lipid peroxide
      (thiobarbituric acid reactive substance) in the colonic mucosa of iron-overload
      mice (Fe 0.07% in diet). The iron concentrations in plasma and cecum contents
      were not affected by administration of B. bifidum strain Yakult. Bifidobacterium
      bifidum strain Yakult had no chelating or incorporating activity for ferrous iron
      in vitro. Therefore, the antioxidative effect of B. bifidum strain Yakult in the
      colonic mucosa was not thought to be based on the removal of ferrous iron from
      the reaction system of lipid peroxidation. These results suggested that B.
      bifidum strain Yakult protected the colonic mucosa from oxidative injury without
      inhibiting iron absorption.

PMID- 11467807
TI  - Validation and comparison of analytical methods based on the release of p
      nitrophenol to determine lipase activity in milk.
AB  - Three methods of determining lipase activity were optimized, validated, and
      compared using skim and whole milk. A chromogenic ester (p-nitrophenyl caprylate)
      was used in all to quantify the enzyme activity through the release of p
      nitrophenol. It was measured colorimetrically (method A) or
      spectrophotometrically (methods B and C) with a clarifying reagent to render the
      samples measurable. Methods B and C differed because an inhibiting mixture was
      used in the latter method to better stop the enzymatic reaction. All the methods
      were reliable; they were linear in the range of 0 to 300 mU/ml of the enzyme, and
      the least detection and quantification limits were 9.31 and 31.03 mU/ml of
      lipase, respectively. Precision, measured as relative standard deviation, was
      between 1.52 and 4.94%, and mean recoveries ranged between 81 and 90%. Linearity,
      sensitivity, and accuracy were significantly different among the methods. Methods
      B and C had better linearity and sensitivity than method A, and the most accurate
      results were obtained with methods A and B in skim milk. Sensitivity was
      influenced by the fat content of the samples. On the other hand, the content of
      lipase did not influence the reliability of any method. Although, all of the
      methods were useful for routine analysis of quality control of milk, method B was
      most reliable. Moreover, it would be the method of choice because it was easier
      and less costly than the other methods.

PMID- 11467808
TI  - Undegradable protein supplementation to early-lactation dairy cows in grazing
      conditions.
AB  - To determine the production responses to rumen undegradable protein (RUP) feeding
      in grazing conditions, we fed 18 multiparous Holstein cows concentrates
      containing either soybean meal (SBM) or blood meal (BM) during the first 8 wk of
      lactation. One cow from the SBM treatment was removed because of mastitis. Six
      additional dairy cows in late lactation fitted with ruminal cannula were used to
      evaluate the rumen environment and the in situ crude protein (CP) degradability
      of concentrates. On a dry matter (DM) basis, concentrates contained SBM (33%) or
      BM (13%), corn grain (64 and 84% for SBM and BM, respectively) and a mineral
      vitamin complex (3%). Concentrates were offered at a rate of 6.6 kg/d per cow and
      herbage allowance averaged 31 kg/d of DM per cow. The BM reduced ruminal ammonia
      N levels and had no effect on ruminal pH and molar volatile fatty acid
      concentration. The degradable fraction (63.59 vs. 22.46%) and the rate of
      disappearance of the CP (9.68 vs. 1.69%/h) were greater for the SBM compared with
      the BM concentrate. Cows fed the BM concentrate produced more milk (29.3 vs. 24.9
      kg/d) and more milk protein (0.85 vs. 0.74 kg/d) than did those fed the SBM
      concentrate. Milk fat yield and percentages of milk fat, lactose and protein were
      not affected. Forage DMI was increased by BM (17.19 vs. 13.17 kg/d per cow). The
      in vivo responsiveness to lipolytic stimuli were increased by BM but enhanced
      body weight loss or higher plasma nonesterified fatty acids concentration were
      not observed. Results indicated that a concentrate with a high RUP content
      increased milk and milk protein yields when spring pasture was the sole forage.
      The highest milk yield was more likely caused by increased DM than by enhanced
      body lipid mobilization.

PMID- 11467809
TI  - Short communication: Consumer evaluation of milk high in conjugated linoleic
      acid.
AB  - A consumer evaluation was undertaken to determine whether there were differences
      in the acceptability of milk from cows fed a control or a fish oil diet. The two
      treatments included a control diet of a 50:50 ratio of forage-to-concentrate and
      fish oil added to the control diet with 2% (on dry matter basis) added fat from
      menhaden fish oil. Milk from cows fed the control or fish oil diet contained 3.31
      and 2.58% fat and 0.56 and 2.30 g of total conjugated linoleic acid/100 g of
      fatty acids, respectively. Consumer evaluation of control and fish oil milks
      found no difference in acceptability.

PMID- 11467810
TI  - DNA sequence analysis of three Lactococcus lactis plasmids encoding phage
      resistance mechanisms.
AB  - The three Lactococcus lactis plasmids pSRQ700, pSRQ800, and pSRQ900 encode the
      previously described anti-phage resistance mechanisms LlaDCHI, AbiK, and AbiQ,
      respectively. Since these plasmids are likely to be introduced into industrial
      Lactococcus lactis strains used to manufacture commercial fermented dairy
      products, their complete DNA sequences were determined and analyzed. The plasmids
      pSRQ700 (7784 bp), pSRQ800 (7858 bp), and pSRQ900 (10,836 bp) showed a similar
      genetic organization including a common lactococcal theta-type replicon. A second
      replication module showing features of the pMV158 family of rolling circle
      replicons was also found on pSRQ700. The theta replication regions of the three
      plasmids were associated with two additional coding regions, one of which encodes
      for HsdS, the specificity subunit of the type I restriction/modification system.
      When introduced into L. lactis IL1403, the HsdS of pSRQ800 and pSRQ900 conferred
      a weak resistance against phage P008 (936 species). These results indicated that
      both HsdS subunits can complement the chromosomally encoded type I
      restriction/modification system in IL1403. The genes involved in the phage
      resistance systems LlaDCHI, AbiK, and AbiQ were found in close proximity to and
      downstream of the replication modules. In pSRQ800 and pSRQ900, transfer origins
      and putative tyrosine recombinases were found upstream of the theta replicons.
      Genes encoding recombination proteins were also found on pSRQ700. Finally, open
      reading frames associated with bacteriocin production were found on pSRQ900, but
      no anti-lactococcal activity was detected. Based on our current knowledge, these
      three plasmids are safe and suitable for food-grade applications.

PMID- 11467811
TI  - Establishment of a simple method for measurement of chronic blood flow in uterine
      artery of pregnant cows.
AB  - Blood flow to the gravid uterine horn of seven multiparous Holstein cows (mean +/
      SD, BW = 625.5 +/- 82.4 kg; age = 4.7 +/- 1.7 yr; parity = 2.9 +/- 1.1 yr) was
      measured from d 225 of gestation to parturition using transit-time ultrasonic
      blood flow probes placed around the middle uterine artery. Surgery was conducted
      on d 215 of gestation. The cows were sedated with xylazine and local anesthesia
      (procaine or bupivacain hydrochloride) during surgery. The surgical operations
      were conducted at the flank of standing cows. A transit time ultrasonic flow
      probe ("S" series, diameter 12 or 14 mm, Transonic Systems Inc., Ithaca, NY) was
      fitted surgically around the uterine artery of each cow. Surgery was completed
      within 2 h of anesthesia, and the animals recovered rapidly following surgery.
      Uterine blood flow (UBF, L/min) was recorded at 10-s intervals for 1395 min;
      these values were averaged to determine UBF. Cows exhibited normal gestation
      lengths (279.1 +/- 7.4 d), gave birth to normal healthy calves (birth weight =
      40.6 +/- 6.6 kg), and had no retained placentas. The UBF increased significantly
      (P < 0.01) from d 225 (6.67 +/- 2.47) to d 249 (8.23 +/- 2.89) of gestation, but
      the latter UBF was similar to that of d 266 (8.38 +/- 2.70). The increased UBF
      after d 225 indicates increased demand of nutrients of fetus with the progress of
      gestation. The range of mean UBF varied widely among individual cows from 4.1
      L/min to 12.2 L/min. Our method is useful for chronic measurement of UBF in cows
      for nutritional or physiological studies and does not require sophisticated
      facilities or special surgical technique.

PMID- 11467812
TI  - Effects of naloxone on calcium turnover in cows affected by milk fever.
AB  - Milk fever is a metabolic disorder of calcium homeostasis that affects about 2 to
      6% of postpartum cows. Current therapy is based on the administration of calcium
      gluconate. On the basis of the clinical signs, and given that endorphins increase
      at parturition, we supposed that endogenous opioid peptides (EOP) could be
      responsible for this pathology. In this study, cows with milk fever were
      administered the opiate antagonist, Naloxone (Nx; experiment 1) or Nx with
      calcium salts (experiment 2). In experiment 1, Nx induced the recovery of
      affected cows. The effects of Nx therapy, expressed in terms of proportion of
      recovered cows, of cows recovering in less than 30 min and cows requiring
      repeated treatments, were not statistically different than those obtained by
      means of calcium administration (17/17, 100%; 10/17, 59% and 7/17, 41% vs. 33/35,
      94%; 22/35, 63% and 11/35, 31%, respectively; NS). In experiment 2, a
      significantly higher ratio of cows recovered in less than 30 min in the group of
      animals treated with Nx in association with calcium salts, compared with the
      group of cows treated with the calcium traditional therapy (106/118, 90% for
      calcium-Nx treated cows vs. 34/62, 55% for calcium-treated cows). Moreover, in
      the group of cows treated with calcium-Nx, the number of cows requiring repeated
      treatments was significantly reduced and no unrecovered cows were observed. The
      results support the idea that high EOP levels interfere with inward movement of
      calcium through the cell membrane and with calcium activity. The association of
      calcium and Nx at low dosage is a safe method to treat milk fever in cows and
      reduces muscular complications.

PMID- 11467813
TI  - An investigation of the impact of intramammary antibiotic dry cow therapy on
      clinical coliform mastitis.
AB  - The efficacy of an intramammary antibiotic dry cow preparation with significant
      gram-negative spectrum (product A; Leo Red Dry Cow, Leo Animal Health, UK) was
      compared with a product with no gram-negative efficacy (product B; Orbenin Extra
      DC, Pfizer Ltd, UK) as assessed by control of coliform mastitis in the first 100
      d of the lactation. The efficacy of both products was also compared for control
      of noncoliform mastitis and for the ability to control existing and new
      intramammary infections as measured by individual cow somatic cell counts. Cows
      treated with product A were significantly less likely to develop clinical
      Escherichia coli or coliform mastitis during the dry period or the first 100 d of
      lactation than cows treated with product B. Cows treated with product A were no
      more likely to develop clinical mastitis due to a noncoliform organism than were
      cows treated with product B. There was no significant difference between the two
      groups as measured by individual cow somatic cell count changes across the dry
      period. This study is the first to have demonstrated the clinical efficacy of an
      intramammary antibiotic dry cow preparation, as measured by reduction in gram
      negative clinical mastitis in the subsequent lactation. These findings
      demonstrate that selection of a dry cow intramammary preparation with a
      significant gram-negative spectrum can influence the incidence of clinical
      coliform mastitis in the subsequent lactation. This finding should be one of the
      factors taken into account when selecting products.

PMID- 11467814
TI  - Detection of Mycoplasma bovis in preservative-treated field milk samples.
AB  - Control of mycoplasmal mastitis requires individual cow milk sampling for culture
      and identification of Mycoplasma bovis. This sampling is time-consuming and
      expensive. Currently, some herds sample cows monthly with the dairy herd
      improvement (DHI) program, but a preservative is added to this milk that kills M.
      bovis. In this paper, a nested polymerase chain reaction (PCR) procedure that
      allows for rapid testing of preservative-treated milk is validated. The
      specificity of the nested PCR assay was confirmed by testing isolated nucleic
      acids of other organisms phylogenetically related to M. bovis or common to milk.
      A comparison against blind-passage culture on 53 field milk samples determined
      its sensitivity. Exposure of seeded milk samples to the procedure resulted in a
      sensitivity of 5.1 cfu equivalents per milliliter. Analysis of these results
      proved that the nested PCR assay was as sensitive as traditional culture and can
      be used on preservative-treated milk.

PMID- 11467815
TI  - Effects of presynchronization and bovine somatotropin on pregnancy rates to a
      timed artificial insemination protocol in lactating dairy cows.
AB  - The objective was to examine the effects of presynchronization and bovine
      somatotropin (bST) on pregnancy rates to a timed artificial insemination protocol
      in lactating dairy cows. Lactating Holstein cows (n = 543) were assigned randomly
      in a 2 x 3 factorial experiment in which cows received a presynchronization
      treatment or not, and were treated with bST (500 mg) at 63 +/- 3, 73 +/- 3, or
      147 +/- 3 d postpartum. The latter group was used as a control.
      Presynchronization treatment consisted of two injections of PGF2alpha (25 mg)
      given 14 d apart, with the second injection of PGF2alpha being administered 12 d
      before initiation of the timed artificial insemination protocol. All cows
      received GnRH (100 microg) at 63 +/- 3 d postpartum, an injection of PGF2alpha
      (40 mg) 7 d later, a GnRH injection at 48 h after PGF2alpha and were inseminated
      16 to 20 h later. Cows were resynchronized if determined to be nonpregnant at
      ultrasonography at 32 d after insemination with a GnRH injection (100 microg), an
      injection of PGF2alpha (40 mg) 7 d later, and a GnRH injection at 48 h after
      PGF2alpha and were inseminated 16 to 20 h later. Cows were examined for pregnancy
      at 32 d and reexamined at 74 d after insemination. No differences in pregnancy
      rates were observed between cows receiving bST treatment at 63 +/- 3 d postpartum
      or at 73 +/- 3 d postpartum. An interaction between presynchronization and bST
      treatment indicated that pregnancy rates were increased for cows treated with bST
      when cows were presynchronized. When anestrous cows were excluded from the
      analyses, both an effect of bST and of presynchronization were observed,
      indicating that bST increased pregnancy rates regardless of presynchronization
      treatment and that presynchronization also increased pregnancy rates
      independently of bST treatment. Presynchronization and bST treatment may be used
      to increase first-service pregnancy rates to a timed artificial insemination
      protocol.

PMID- 11467816
TI  - Effect of weaning system on commercial milk production and lamb growth of East
      Friesian dairy sheep.
AB  - East Friesian crossbred ewes (n = 99) and their lambs (n = 232) were used to
      study the effects of three weaning systems on milk production and lamb growth.
      Prior to parturition, a ewe and her lambs were assigned to one of the following
      three treatments for the first 28 +/- 3 d of lactation: 1) ewes weaned from their
      lambs at 24 h postpartum, ewes machine milked twice daily, and their lambs raised
      artificially (DY1); or 2) beginning 24 h postpartum, ewes separated from their
      lambs for 15 h during the evening, ewes machine milked once daily in the morning,
      and their lambs allowed to suckle for 9 h during the day (MIX); or 3) ewes not
      machine milked and exclusively suckled by their lambs (DY30). After the treatment
      period, lambs were weaned from MIX and DY30 ewes, and all three groups were
      machine milked twice daily. Daily commercial milk yield and milk composition were
      recorded weekly or twice monthly, and lambs were weighed at weaning or at 28 d
      and at approximately 120 d of age. Average lactation length (suckling + milking
      period) was 183 +/- 5 d and was similar among weaning systems. Differences among
      weaning systems for milk yield, milk fat and protein percentages, and somatic
      cell count were highly significant prior to and around weaning, and became
      nonsignificant by 6 wk in lactation. Total commercial milk production was
      greatest for DY1 and MIX ewes (261 +/- 10 and 236 +/- 10 kg/ewe, respectively)
      and least for DY30 ewes (172 +/- 10 kg/ewe). Daily gain of lambs to 30 d and
      weight at 30 d were similar regardless of weaning system; however, by 120 d, DY30
      lambs tended to be heaviest, MIX lambs intermediate, and DY1 lambs lightest (47.3
      +/- 1.6, 45.9 +/- 1.8, and 43.7 +/- 1.2 kg, respectively). Overall financial
      returns for milk and lamb sales were greatest for the MIX system because of the
      increase in marketable milk during the first 30 d of lactation compared with the
      DY30 system and because of acceptable 120-d lamb weights without the expenses of
      artificial rearing compared with the DY1 system. A mixed system of suckling and
      milking during early lactation appears to be a valuable management tool for dairy
      sheep production.

PMID- 11467817
TI  - Nutritionally directed compensatory growth enhances heifer development and
      lactation potential.
AB  - The objectives of this study were 1) to examine the interactive influence of a
      compensatory nutrition regimen and lasalocid supplementation on dairy heifer
      growth performance and 2) to document the extent to which compensatory growth
      sustains lactation potential over the first two lactation cycles. Twelve Holstein
      heifers, weighing an average of 160 kg (about 6 mo of age) were randomly assigned
      to treatments arranged in a 2 x 2 factorial design. Treatment variables were two
      dietary regimens (control and stair-step compensatory nutrition) and two levels
      of lasalocid (0 and 200 mg/d). The control heifers were fed a diet containing 12%
      crude protein (CP) and 2.35 Mcal of metabolizable energy (ME) per kilogram of dry
      matter. The stair-step compensatory nutrition heifers were subjected to a phased
      nutrition regimen and reared according to an alternating 3-2-4-3-4-2-mo schedule.
      The first stair-step (prepubertal phase) consisted of energy restriction [17% CP
      and 2.35 Mcal/kg of ME] for 3 mo followed by realimentation (12% CP and 3.05
      Mcal/kg of ME) for 2 mo. The second step (puberty and breeding) consisted of
      energy restriction for 4 mo followed by realimentation for 3 mo. The third step
      (gestation period) was energy restriction for 4 mo concluding with realimentation
      for 2 mo. Dry matter intake of heifers during the restriction phase was limited
      to 70% of the control intake. Heifers were given ad libitum access to a high
      energy density diet during realimentation to allow compensatory development.
      Stair-step heifers supplemented with lasalocid had the highest efficiency of
      growth (body weight gain/dry matter intake), suggesting synergistic metabolism of
      lasalocid with compensatory growth action. Compensatory growth induced during the
      last trimester enhanced metabolic status by increasing circulating insulin and
      decreasing triglyceride levels. Heifers on the stair-step regimen had a
      significant increase in milk yield during the first (21%) and second (15%)
      lactation cycles. These results support our thesis that compensatory growth
      induced during an allometric growth phase improves mammary development and energy
      and protein metabolic status of dairy heifers.

PMID- 11467818
TI  - Influence of supplemental chromium on concentrations of liver triglyceride, blood
      metabolites and rumen VFA profile in steers fed a moderately high fat diet.
AB  - This study evaluated the effects of supplemental Cr on liver triglycerides and
      blood metabolites in Holstein steers fed a moderately high fat (approximately
      5.6% of dry matter) diet. Fourteen Holstein steers were blocked by BW and
      randomly assigned to a basal diet (control) or control diet supplemented with 0.8
      mg/kg of Cr as chromium picolinate. Supplemental Cr had no effect on dry matter
      intake, average daily gain, serum glucose, insulin, cholesterol, and molar
      proportions of ruminal volatile fatty acids (VFA). Steers fed the diet
      supplemented with chromium picolinate had smaller concentrations of serum
      triglycerides at wk 3, plasma beta-hydroxybutyrate concentrations at wk 6, and
      liver triglycerides at wk 9. An in vitro mixed ruminal microorganism fermentation
      study was conducted to examine the effect of Cr on in vitro VFA production.
      Ruminal fluid from animals fed fescue hay and 1.1 kg of concentrate twice daily
      was added into a mixture containing 5 g of concentrate diet formulated to contain
      one of five concentrations of Cr (0, 0.2, 0.4, 0.8, or 1.6 mg/kg of Cr). The
      culture was incubated for 12 or 24 h. The molar proportion of propionate
      decreased, whereas butyrate and isobutyrate increased linearly with increasing Cr
      content at 12 h of incubation. Molar proportion of valerate alone increased
      linearly with increasing Cr content at 24 h of incubation. A second in vitro
      study evaluated the supplementation of Cr at concentrations of 0, 0.8, 1.6, 3.2,
      6.4, 12.8, or 25.6 mg/kg. Molar proportions of acetate, propionate, and
      isovalerate, and total VFA production responded quadratically with increasing Cr
      content at 24 h. Results suggest that supplemental Cr may alter systemic lipid
      metabolism. In vitro fermentation altered VFA production with graded
      concentration of Cr and was not toxic to ruminal microorganisms at concentrations
      up to 25.6 mg/kg.

PMID- 11467819
TI  - Effect of protein source and soluble carbohydrate addition on rumen fermentation
      and lactation performance of Holstein cows.
AB  - Rumen in vitro and in vivo experiments were conducted to evaluate the effect of
      rumen undegradable protein and soluble carbohydrates on rumen ammonia N release
      and lactation performance of Holstein cows. In the in vitro experiment, freeze
      dried annual ryegrass (Lolium multiflorum, LAM) pasture was supplemented 1:1 with
      ground corn-based grain supplements containing expeller or solvent soybean meal
      with sucrose or lactose supplements at 0, 2.5, or 5% of dry matter (DM). The
      ammonia release rate was slower with expeller compared with solvent soybean meal
      supplemented diets. Sucrose supplementation at the 5% level lowered rumen ammonia
      concentrations, but lactose-fortification of grain supplements was without
      effect. In the in vivo study, 32 multiparous Holstein cows were blocked according
      to milk yield and randomly assigned to corn-based grain supplements containing 1)
      solvent soybean meal, 2) solvent soybean meal + 5% sucrose supplement, 3)
      expeller soybean meal, or 4) expeller soybean meal + 5% sucrose supplement. Grain
      supplements and fresh annual ryegrass were component fed at approximately a 1:1
      grain to forage ratio (DM basis). Forage DM intake was higher for cows receiving
      solvent soybean meal supplemented grain supplements than those receiving expeller
      soybean meal (12.2 +/- 2.1 vs. 11.4 +/- 2.2 kg/d), but total DM intake was
      similar for all diets (22.8 +/- 2.9 kg/d). Fat-corrected milk yield was similar
      for all diets averaging 37.5, 38.2, 39.1, and 37.6 kg/d for diets 1 to 4,
      respectively. Rumen fermentation, milk urea nitrogen, and body condition were
      unaffected by supplements; however, cows fed grain supplement 1 utilized dietary
      energy more efficiently than cows offered the other dietary treatments. High
      dietary crude protein concentrations may have limited lactation response to rumen
      undegradable protein and sugar.

PMID- 11467820
TI  - Effects of NutriDense and waxy corn hybrids on the rumen fermentation,
      digestibility and lactational performance of dairy cows.
AB  - The objectives of this study were to determine the effects of NutriDense and waxy
      corn hybrids as silage and grain sources on milk yield, milk composition,
      digestibility of dietary components, and rumen characteristics. Six multiparous
      (intact) and six primiparous (ruminally cannulated) Holstein cows were assigned
      at 72 to 90 d of lactation to a 3 x 6 Latin rectangle design experiment to
      treatment of: 1) control diet, 2) NutriDense corn diet, and 3) waxy corn diet.
      Diets consisted of 10.9% alfalfa silage, 32.8% corn silage, 27.9% cracked corn
      grain, and 28.4% other ingredients (DM basis). Milk, FCM, and milk fat and
      protein yields were higher for cows fed the waxy diet than those fed the control
      diet. Milk protein percentage tended to be higher for cows fed the control and
      waxy diets than those fed the NutriDense diet. Dry matter intake tended to be
      higher for cows fed the waxy diet than the NutriDense diet. Apparent DM, OM, CP,
      ADF, NDF, and gross energy digestibilities were similar among dietary treatments,
      while apparent starch digestibility was higher for the waxy corn than for the
      NutriDense corn. Rumen NH3-N concentration was higher for cows fed the NutriDense
      diet than for those fed the control and waxy diets. The proportion of ruminal
      propionate was higher for the waxy diet than the control diet. NutriDense and
      waxy corn hybrids can be effective substitutes for conventional yellow dent corn
      hybrids in lactating dairy cow rations.

PMID- 11467821
TI  - Influence of carbohydrate source and buffer on rumen fermentation
      characteristics, milk yield, and milk composition in late-lactation Holstein
      cows.
AB  - The effects of concentrate-to-forage ratio and buffer on rumen fermentation and
      production parameters were examined in four rumen-cannulated cows (240 +/- 18 d
      in milk) fed a total mixed ration ad libitum in a 4 x 4 Latin square design. The
      treatments were a 50:50 concentrate to forage ratio with [1.2% of dry matter,
      (DM)] and without (0% of DM) buffer and a 75:25 concentrate to forage ratio with
      (1.2% of DM) and without (0% of DM) buffer. Rumen pH declined in response to
      increased concentrate but was not influenced by buffer. In the absence of the
      buffer, rumen acetate declined and propionate was elevated at the higher level of
      concentrate inclusion. The milk fat concentration was lower for cows fed the high
      concentrate diet without buffer; however, the addition of buffer to the diet
      prevented the milk fat depression. Milk fat depression was associated with
      elevated trans-C18:1 fatty acids in milk, which provides additional support for
      an inhibitory effect of these fatty acids on mammary fat synthesis. We concluded
      that the potential of nutrition as a tool to alter milk composition is greater in
      later lactation as these animals are better able to cope with the negative
      effects of high grain diets, and the treatment response is greater than in early
      lactation.

PMID- 11467822
TI  - Effect of monensin on the performance and nitrogen utilization of lactating dairy
      cows consuming fresh forage.
AB  - We conducted a lactation trial with a fresh forage diet in order to evaluate 1)
      the effects of monensin on nitrogen metabolism, and 2) the Cornell Net
      Carbohydrate and Protein System (CNCPS). Thirty Holstein cows in midlactation
      (eight fitted with ruminal fistulas) were gradually introduced to a fresh forage
      diet. A concentrate mix based on corn meal was fed before the a.m. and p.m.
      milking times 0730 and 1730 h, then the fresh forage was fed at 0830 and 1830 h.
      Fifteen cows each were allocated to a control (no monensin) and a treatment group
      receiving 350 mg/cow per day of monensin in the p.m. concentrate feeding. A 7-d
      fecal and urine collection period and a 3-d rumen sampling period were conducted
      with the fistulated cows. After the lactation study was concluded, the fistulated
      cows were fed forage regrowth and a 3-d rumen sampling period was repeated.
      Monensin increased milk production by 1.85 kg. Milk fat and protein
      concentrations decreased and milk fat and protein yields increased, but the
      effects were nonsignificant. Monensin did not significantly affect DMI. Ruminal
      ammonia and the acetate-to-propionate ratio decreased with the addition of
      monensin in both fed forages. Monensin decreased fecal N output, and increased
      apparent N digestibility by 5.4%. Because of the decrease in ruminal ammonia and
      increase in apparent N digestibility, we concluded monensin was sparing amino
      acids from wasteful rumen degradation with a fresh forage diet. The precision of
      the CNCPS in predicting performance was high (r2 = 0.76), and the bias was low
      (overprediction of 3.6%). These results indicate that the CNCPS can be used for
      dairy cows consuming fresh forage and gives realistic predictions of performance.

PMID- 11467823
TI  - Production of lactating dairy cows fed alfalfa or red clover silage at equal dry
      matter or crude protein contents in the diet.
AB  - Two Latin square trials, using 21 or 24 multiparous lactating Holstein cows,
      compared the feeding value of red clover and alfalfa silages harvested over 2 yr.
      Red clover silages averaged 2 percentage units lower in crude protein (CP) and
      more than 2 percentage units lower in neutral detergent fiber and acid detergent
      fiber than did alfalfa silage. In trial 1, diets were formulated to 60% dry
      matter (DM) from alfalfa, red clover silage, or alfalfa plus red clover silage
      (grown together); CP was adjusted to about 16.5% by adding soybean meal, and the
      balance of dietary DM was from ground high moisture ear corn. Nonprotein N in red
      clover and alfalfa-red clover silages was 80% of that in alfalfa silage. Although
      DM intake was 2.5 and 1.3 kg/d lower on red clover and alfalfa plus red clover,
      yield of milk and milk components was not different among diets. In trial 2, four
      diets containing rolled high moisture shelled corn were formulated to 60% DM from
      alfalfa or red clover silage, or 48% DM from alfalfa or red clover silage plus
      12% DM from corn silage. The first three diets contained 2.9% soybean meal, and
      the red clover-corn silage diet contained 5.6% soybean meal; the 60% alfalfa diet
      contained 18.4% CP, and the other three diets averaged 16.5% CP. Nonprotein N in
      red clover silage was 62% of that in alfalfa silage. Intake of DM was about 2 (no
      corn silage) and 1 kg/d (plus corn silage) lower on red clover. Yield of milk and
      milk components was not different among the first three diets; however, yields of
      milk, total protein, and true protein were higher on red clover-corn silage with
      added soybean meal. Replacing alfalfa with red clover improved feed and N
      efficiency and apparent digestibility of DM, organic matter, neutral detergent
      fiber, acid detergent fiber, and hemicellulose in both trials. Net energy of
      lactation computed from animal performance data was 18% greater in red clover
      than alfalfa. Data on milk and blood urea and N efficiency suggested better N
      utilization on red clover.

PMID- 11467824
TI  - Milk production, estimated phosphorus excretion, and bone characteristics of
      dairy cows fed different amounts of phosphorus for two or three years.
AB  - Diets containing 0.31, 0.39, or 0.47% P on a DM basis were fed to 10, 14, and 13
      multiparous Holstein cows, respectively, for a full lactation. Most of the cows
      (33) were fed similar amounts of P in the previous one or two lactations. The
      objective was to obtain information on bone integrity after prolonged feeding of
      different amounts of P. At the end of the experiment, a section (-20 cm) of the
      12th rib was surgically removed. The bone was tested for strength and analyzed
      for ash and P content. The shear strength and the energy required to deform the
      bone to the point of fracture did not differ among treatments. Bone specific
      gravities were 1.50, 1.57, and 1.55 for the three treatments. Ash and P content
      of the bone, measured in wet weight, dry weight, and wet bone volume, were
      similar for the 0.39 and 0.47% P treatments, but tended to be lower with the
      0.31% P treatment. Milk production of cows in all groups was high, averaging
      >11,900 kg for the 308-d lactation. Feeding P at 0.31% of dietary DM over two to
      three lactations appeared to decrease P concentration of bone, but the decrease
      was not severe enough to affect bone strength. Dietary P at 0.39% did not affect
      bone P content or strength. Dietary P content of 0.31% appears to be borderline
      deficient for cows producing >11,900 kg/308 d.

PMID- 11467825
TI  - Evaluation of clinical and clinical chemical parameters in periparturient cows.
AB  - Certain blood parameters and clinical symptoms have been connected with milk
      fever and a hypocalcemic condition in the cow. The present study intended to
      establish a mutual connection between relevant blood parameters and potentially
      valuable background information about the cow and its observed clinical symptoms
      at calving. Two veterinarians were summoned within 12 h of parturition of 201
      cows, distributed among 41 Danish commercial herds. Cows were at different parity
      levels (2 to 10) and breeds and management differed broadly among herds. A blood
      sample was taken from the vena jugularis or the tail vein and was subsequently
      analyzed in the laboratory. Furthermore, 13 different clinical symptoms were
      recorded as categorical data. We investigated associations among the data
      obtained. We assessed an interpretative model for actual blood calcium level with
      blood parameters and background knowledge of the animals. We established a path
      analysis using background knowledge, blood parameters, and results of clinical
      examinations to uncover causal connections among the variables. Twenty-six
      percent of the animals were diagnosed as having milk fever and subsequent blood
      analyses revealed a high frequency of hypocalcemia within the general range from
      0.69 to 2.73 mmol of Ca per liter. Rectal temperature, inorganic blood phosphate,
      and potassium were all directly correlated with blood calcium, while glucose,
      lactate, and magnesium were inversely associated with calcium. Blood osteocalcin
      was significantly lower in hypocalcemic animals, indicating that de novo
      synthesis of bone was arrested during hypocalcemia. A mixed effect linear
      interpretative model explained 75% of the variation in blood calcium. Clinical
      symptoms like mood, appetite, muscle shivering, rumen motility, and paresis were
      individually correlated with blood calcium and were thereby predictive of
      hypocalcemia. The path analysis showed the central role of calcium in affecting
      the clinical symptoms. However, several other factors contributed to
      hypocalcemia.

PMID- 11467826
TI  - Weighting factors of sire daughter information in international genetic
      evaluations.
AB  - International genetic evaluations of dairy bulls are currently based on national
      genetic evaluation results. Total number of daughters in a country is used to
      weight national information, but may not optimally reflect the precision of a
      sire's daughter contribution to international genetic evaluations. This study
      investigates the impact of alternative weighting factors on international
      evaluation results. A conventional progeny test scheme was simulated for two
      dairy cattle populations, with semen exchange at a fixed rate after each
      generation. True breeding values for both populations were generated as bivariate
      normal deviates. Each cow had three lactation records in one country only. After
      10 generations of selection, all records were used in national breeding value
      prediction. National breeding values of bulls were used as input to international
      evaluations. Seven different weighting factors were evaluated: 1) total number of
      daughters; 2) total number of lactations; 3) as (one) also adjusted for finite
      contemporary group size; 4) as (three) also adjusted for distribution of
      daughters over contemporary groups; 5) effective daughter contribution
      considering finite contemporary group size and correlation between repeated
      records; 6) as (five) also considering the reliability of the daughter dam
      evaluation; and 7) as (five) also considering the reliability of the daughter
      female ancestors' evaluations. Using the last two weighting factors yielded
      empirically unbiased estimates of sire variance. Using total number of daughters
      overestimated genetic variance by up to 7%. In general, international breeding
      values were marginally affected by choice of weighting factor. The effect was
      larger when different national evaluation models had been applied in the two
      countries. International reliabilities for the last two weighting factors were
      close to expectation, whereas using total number of daughters resulted in 1 to 4%
      negative bias. In practice, different countries apply a wide range of national
      evaluation models, and genetic ties may be weak between some populations, thereby
      increasing the potential effect of weighting factors on international
      comparisons. The weighting factor developed in this study, which considers
      contemporary group structure, correlation between repeated records, and
      reliability of dams of daughters, should replace total number of daughters in
      international genetic evaluations of dairy sires.

PMID- 11467827
TI  - Two breed-specific bovine MC1-R alleles in Brown Swiss and Saler breeds.

PMID- 11467828
TI  - The isochores in human chromosomes 21 and 22.

PMID- 11467829
TI  - Relationship between kinetic and equilibrium folding intermediates of creatine
      kinase.
AB  - Creatine kinase (CK) is a dimeric enzyme important in ATP regeneration in cells
      where energy demands are high. The folding of CK under equilibrium and transient
      conditions has been studied in detail and is found to be complex. At equilibrium
      in 0.8 M GuHCl, 90% of CK molecules are in the form of a partially structured,
      monomeric intermediate. We exploit this property to measure kinetics of refolding
      and unfolding to and from this equilibrium intermediate (EI), using far-UV
      circular dichroism and intrinsic fluorescence as structural probes. We are thus
      able to compare the properties of EI and the kinetic intermediate formed during
      the burst phase in refolding. Native CK and EI unfold with rate constants in
      seconds and milliseconds, respectively. As is observed for refolding of fully
      denatured CK, refolding from EI to the native state shows a burst phase followed
      by two exponential phases. The burst phase refolding intermediate is inferred to
      have more structure and greater stability than the equilibrium intermediate. When
      refolding from the fully-denatured state in 0.8 M GuHCl, the equilibrium
      intermediate is formed within the dead-time of mixing in the stopped-flow
      apparatus. The equilibrium intermediate may thus represent a kinetic intermediate
      formed early during folding.

PMID- 11467830
TI  - Human monocytes possess a serine protease activity capable of degrading HIV-1
      reverse transcriptase in vitro.
AB  - Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) plays a
      central role in the virus replication cycle. We found that HIV-1 RT was rapidly
      degraded when incubated with cell extracts obtained from human peripheral blood
      cells. The proteolytic activity responsible for the in vitro degradation of RT
      was present in monocytes and their precursors. Interestingly, this activity was
      downregulated upon cell activation or differentiation along the macrophage
      pathway. The proteolytic process appears specific for HIV-1 RT since other HIV-1
      proteins were not degraded upon incubation in the same extracts. Although the
      degradation of RT was unaffected by specific proteasome inhibitors, it could be
      inhibited by PMSF and aprotinin, suggesting the involvement of a serine protease.
      Upon cell fractionation, this serine protease was found to be associated with the
      microsomal fraction and displayed an apparent molecular weight of approximately
      2000 kDa, as determined by gel filtration. Our results suggest that a giant
      serine protease, different from tripeptidyl peptidase II, is involved in the in
      vitro degradation of HIV-1 RT. The possibility of an in vivo interaction between
      HIV-1 RT and a cell-type-specific serine protease is discussed.

PMID- 11467831
TI  - Inhibition of ChoK is an efficient antitumor strategy for Harvey-, Kirsten-, and
      N-ras-transformed cells.
AB  - An increasing amount of evidence suggests that elevated PCho levels are related
      to the transforming properties of the H-Ras oncoprotein. Based on these
      observations, we have designed an antitumor strategy using choline kinase, the
      enzyme responsible of PCho production, as a novel target for drug discovery.
      However, little relationship between this lipid-related pathway and the other two
      Ras members, N- and K-ras, has been established. Since N- and K-ras are the most
      frequently mutated ras genes in human tumors, we have analyzed the PC-PLD/ChoK
      pathway and the sensitivity to ChoK inhibition of all three ras-transformed
      cells. Here we demonstrate that transformation by the three Ras oncoproteins
      results in increased levels of PCho to a similar extent, resulting from a similar
      constitutive increase of ChoK activity. As well, sensitivity to choline kinase
      inhibitors as antiproliferative drugs is similar in cell lines transformed by
      each of the three ras oncogenes, being in all cases higher than parental,
      nontransformed cells. In addition, H, K and N-ras-induced alterations in PC
      metabolism is discussed. These results indicate that ChoK can be used as a
      general target for anticancer drug design against Ras-dependent tumorigenesis.

PMID- 11467832
TI  - Forskolin activation of apical Cl- channel and Na+/K+/2Cl- cotransporter via a
      PTK-dependent pathway in renal epithelium.
AB  - Forskolin induced the transepithelial Cl- transport (secretion) by activating the
      apical Cl- channel and basolateral Na+/K+/2Cl- cotransporter in renal epithelial
      A6 cells via an increase in cytosolic cAMP concentration. The cAMP activation of
      apical Cl- channel and Na+/K+/2Cl- cotransporter was partially mediated through a
      protein kinase A (PKA)-dependent pathway, but a PKA-independent pathway was also
      suggested to be involved in the cAMP activation. Therefore, we assessed a
      possibility of involvement of protein tyrosine kinase (PTK)-dependent pathway as
      a PKA-independent pathway in the cAMP activation by applying a PTK inhibitor,
      tyrphostin A23 (AG18). Tyrphostin A23 abolished the forskolin-induced
      transepithelial Cl- secretion by partially diminishing the activity of the Cl-
      channel and completely inhibiting the Na+/K+/2Cl- cotransporter. Further,
      forskolin increased phosphorylation of protein tyrosine, suggesting that cAMP
      activates PTK. These observations suggest that cAMP activates the Cl- channel and
      the Na+/K+/2Cl- cotransporter by activating PTK.

PMID- 11467833
TI  - An Ochrobactrum anthropi gene conferring paraquat resistance to the heterologous
      host Escherichia coli.
AB  - A new gene, pqrA, conferring paraquat resistance to the heterologous host
      Escherichia coli, from a chromosomal DNA library of Ochrobactrum anthropi JW2,
      was cloned and analyzed. Cells of E. coli transformed with a plasmid carrying the
      pqrA gene showed elevated resistance to paraquat, but not to hydrogen peroxide.
      The predicted amino acid sequence of the PqrA polypeptide showed 71% identity
      with mll7495 hypothetical membrane protein in Mesorhizobium loti, 49% identity
      with PA2269 protein in Pseudomonas aeruginosa, and significant identity with
      other previously reported drug transport proteins. The hydropathy pattern of the
      PqrA polypeptide showed a significant homology to those of 12-transmembrane
      segment (TMS) family export proteins. Immunoblot analysis demonstrated that the
      PqrA protein found in the membrane protein fraction of O. anthropi JW2 has a
      molecular mass of 42 kDa. These results suggest that the PqrA protein is a
      membrane protein that plays an important role in protecting cells against
      paraquat toxicity.

PMID- 11467834
TI  - Reversible integration of the dominant negative retinoid receptor gene for ex
      vivo expansion of hematopoietic stem/progenitor cells.
AB  - Since hematopoietic stem cells (HSCs) differentiate readily ex vivo resulting in
      the loss of self-renewal and engraftment abilities, the transient block of
      differentiation is essential to maintain those abilities during their ex vivo
      expansion culture. To this end, we developed a method of reversible integration
      of the dominant negative retinoic acid receptor (DN-RAR) gene, a differentiation
      blocking gene, into cells utilizing the Cre/loxP-dependent gene recombination
      system. The murine immature hematopoietic 32D cells differentiate into mature
      neutrophils upon G-CSF treatment. However, 32D cells transduced with a retroviral
      vector expressing the DN-RAR gene put between two loxP sites continued to
      proliferate without showing differentiation even in the presence of G-CSF. After
      the cells were fully amplified, the cells were transduced with the Cre
      recombinase gene. The cells then restored the ability to differentiate into
      mature neutrophils upon G-CSF treatment. PCR analysis showed that the DN-RAR gene
      was efficiently removed from the genome by introduction of the Cre gene. This
      system may eventually be applicable to the ex vivo expansion of HSCs.

PMID- 11467835
TI  - Differential regulation of endogenous glucose-6-phosphatase and
      phosphoenolpyruvate carboxykinase gene expression by the forkhead transcription
      factor FKHR in H4IIE-hepatoma cells.
AB  - The insulin responsive H4IIEC3 rat hepatoma cell line (H4 cells) was used in
      order to determine the role of the transcription factor FKHR in the regulation of
      phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase).
      Both PEPCK and G6Pase contain putative FKHR binding sites in their promoter
      sequence. Using a retroviral expression system, we stably overexpressed FKHR in
      H4-cells. FKHR was phosphorylated in a PI 3-kinase- and Akt-dependent manner, and
      was translocated from the nucleus to the cytoplasm in response to insulin.
      Furthermore, overexpression of FKHR markedly increased the expression of the
      catalytic subunit of G6Pase (basal about 2.5-fold, dexamethasone/cAMP stimulated
      about fivefold, respectively). In contrast, both basal and dexamethasone/cAMP
      induced levels of PEPCK mRNA were unaffected by FKHR-overexpression. These data
      suggest a specific function for FKHR in the regulation of hepatic gluconeogenesis
      at the level of G6Pase, but not PEPCK gene expression.

PMID- 11467836
TI  - Codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR)
      amyloidosis.
AB  - Protein material was extracted from amyloid-rich sections of formalin-fixed and
      paraffin-embedded heart tissue from an individual with senile systemic
      amyloidosis, known to contain wild-type transthyretin as major amyloid fibril
      protein. Amino acid sequence analysis of tryptic peptides of this material
      revealed in addition to transthyretin sequences, also amino acid sequence
      corresponding to an N-terminal fragment of apolipoprotein A-IV. In
      immunohistochemistry, an antiserum to a synthetic apolipoprotein A-IV peptide
      labeled amyloid specifically. This peptide formed spontaneously amyloid-like
      fibrils in vitro and enhanced fibril formation from wild-type transthyretin. We
      conclude that several apolipoproteins, including apolipoprotein A-IV, may be
      important minor amyloid constituents, promoting fibril formation.

PMID- 11467837
TI  - Angiogenin activates human umbilical artery smooth muscle cells.
AB  - Angiogenin stimulates proliferation of human umbilical artery smooth muscle
      cells. This activity of angiogenin depends on the cell density and requires
      nuclear translocation of the ligand as well as activation of SAPK/JNK MAP kinase.
      Angiogenin binds to a 170-kDa putative receptor on the cell surface and induces
      phosphorylation of SAPK/JNK. It also undergoes nuclear translocation in a time
      and concentration dependent manner. Neomycin inhibits nuclear translocation of
      angiogenin and abolishes angiogenin-induced cell proliferation but does not
      inhibit SAPK/JNK phosphorylation. The data demonstrate that smooth muscle cells
      are targets for angiogenin and that both SAPK/JNK phosphorylation and nuclear
      translocation of the ligand are required for angiogenin to activate smooth muscle
      cells.

PMID- 11467838
TI  - Chromium(III)-mediated structural modification of glycoprotein: impact of the
      ligand and the oxidants.
AB  - The interaction of three types of chromium(III) complexes, [Cr(salen) (H2O2]+,
      [Cr(en)3]3+, and [Cr(EDTA) (H2O)]- with AGP has been investigated. [Cr(salen)
      (H2O2]+, [Cr(en)3]3+ and [Cr(EDTA) (H2O]- bind to Human alpha1-acid glycoprotein
      with a protein:metal ratio of 1:8, 1:6, and 1:4, respectively. The binding
      constant, K(b) was estimated to be 1.37 +/- 0.12 x 10(5) M(-1), 1.089 +/- 0.05 x
      10(5) M(-1) and 5.3 +/- 0.05 x 10(4) M(-1) for [Cr(salen) (H2O2]+, [Cr(en)3]3+,
      and [Cr(EDTA) (H2O)]-, respectively. [Cr(en)3]3+ has been found to induce
      structural transition of AGP from the native twisted beta sheet to a more compact
      alpha-helix. The complexes, [Cr(salen) (H2O2]+ and [Cr(EDTA) (H2O]-, in the
      presence of H2O2, have been found to bring about nonspecific cleavage of AGP,
      whereas [Cr(en)3]3+ does not bring about any protein damage. Treatment of
      [Cr(salen) (H2O)2]+-protein adduct with iodosyl benzene on the other hand led to
      site specific cleavage of the protein. These results clearly demonstrate that
      protein damage brought about by chromium(III) complexes depends on the nature of
      the coordinated ligand, nature of the metal complex, and the nature of the
      oxidant.

PMID- 11467839
TI  - Protective effects of aspirin and vitamin E (alpha-tocopherol) against copper-
      and cadmium-induced toxicity.
AB  - A 24-h exposure to copper (400 microM, 600 microM) or cadmium (5 microM, 10
      microM) significantly reduces the viability of COS-7 cells. A 2-h preincubation
      with vitamin E does not protect COS-7 cells from copper-induced toxicity, but
      does protect against cadmium-induced toxicity. Preincubation with aspirin
      protects cells from both copper- and cadmium-induced toxicity. A combination of
      aspirin and vitamin E (10 microM and 25 microM, respectively) increases cell
      viability in copper-exposed cells in a clearly additive manner, while in cadmium
      exposed cells the effects are slightly additive. These results indicate that
      aspirin and vitamin E can protect cells from metal-induced toxicity. Differences
      in the protective effects of aspirin and vitamin E on copper versus cadmium
      induced toxicity may be due to alternative mechanisms of metal toxicity or
      antioxidant activity.

PMID- 11467840
TI  - YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes
      and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes.
AB  - YKL-40 (cartilage gp-39), is a mammalian glycoprotein related in sequence to
      chitinases. Its function is unknown, but it is thought to be involved in tissue
      remodeling. Immunocytochemical staining of YKL-40 in guinea pig chondrocytes
      (GPC), rabbit chondrocytes (RC), and rabbit synoviocytes (RS) was higher in
      dividing cells than in confluent cells, suggesting a participation of YKL-40 in
      cell cycle events. As assessed by the MTT assay, YKL-40 at 1.9-7.6 nM had dose
      dependent mitogenic activity toward the three cell types. At 7.6 nM, YKL-40
      increased the number of cells of 42% in GPC, 75% in RC, and 86% in RS after 72 h.
      YKL-40 also stimulated total proteoglycan synthesis by chondrocytes in a dose
      dependent manner as assessed by Na[35SO4] incorporation and cetylpyridinium
      chloride precipitation. At 9.4 nM, YKL-40 increased proteoglycan synthesis of 42%
      in GPC and 58% in RC after 24 h. The growth factor properties of YKL-40 may
      explain the increased tissue remodeling associated with high levels of YKL-40 in
      joint diseases, and possibly, in malignant pathologies such as breast cancer or
      colorectal cancer.

PMID- 11467841
TI  - Proteolysis of ProPTHrP(1-141) by "prohormone thiol protease" at multibasic
      residues generates PTHrP-related peptides: implications for PTHrP peptide
      production in lung cancer cells.
AB  - The parathyroid hormone-related protein (PTHrP) precursor requires proteolytic
      processing to generate PTHrP-related peptide products that possess regulatory
      functions in the control of PTH-like (parathyroid-like) actions and cell growth,
      calcium transport, and osteoclast activity. Biologically active peptide domains
      within the PTHrP precursor are typically flanked at their NH2- and COOH-termini
      by basic residue cleavage sites consisting of multibasic, dibasic, and monobasic
      residues. These basic residues are predicted to serve as proteolytic cleavage
      sites for converting the PTHrP precursor into active peptide products. The
      coexpression of the prohormone processing enzyme PTP ("prohormone thiol
      protease") in PTHrP-containing lung cancer cells, and the lack of PTP in cell
      lines that contain little PTHrP, implicate PTP as a candidate processing enzyme
      for proPTHrP. Therefore, in this study, PTP cleavage of recombinant proPTHrP(1
      141) precursor was evaluated by MALDI mass spectrometry to identify peptide
      products and cleavage sites. PTP cleaved the PTHrP precursor at the predicted
      basic residue cleavage sites to generate biologically active PTHrP-related
      peptides that correspond to the NH2-terminal domain (residues 1-37) that
      possesses PTH-like and growth regulatory activities, the mid-region domain
      (residues 38-93) that regulates calcium transport, and the COOH-terminal domain
      (residues 102-141) that modulates osteoclast activity. Lack of cleavage at other
      types of amino acids demonstrated the specificity of PTP processing at basic
      residue cleavage sites. Overall, these results demonstrate the ability of PTP to
      cleave the PTHrP precursor at multibasic, dibasic, and monobasic residue cleavage
      sites to generate active PTHrP-related peptides. The presence of PTP
      immunoreactivity in PTHrP-containing lung cancer cells suggests PTP as a
      candidate processing enzyme for the PTHrP precursor.

PMID- 11467842
TI  - Rat prominin, like its mouse and human orthologues, is a pentaspan membrane
      glycoprotein.
AB  - Mouse prominin is the first characterized member of a novel family of membrane
      glycoproteins. It displays a characteristic membrane topology with five
      transmembrane segments and two large glycosylated extracellular loops. Prominin
      orthologues and paralogues have been identified in human, fish, fly, and worm.
      Recently, a cDNA sequence encoding the rat homologue of mouse prominin has been
      reported [Zhu et al. (2001) Biochem. Biophys. Res. Commun. 281, 951-956].
      Surprisingly, due to a single nucleotide deletion that shifts the reading frame
      and introduces a premature stop codon, the protein predicted from this cDNA would
      correspond to a C-terminally truncated form of prominin with only four
      transmembrane segments. Here we report evidence that is in contrast to the report
      of Zhu et al. (2001). We isolated a rat prominin cDNA devoid of any frameshift
      mutation, demonstrate that rat prominin, like the other mammalian prominins, is a
      full-length 120-kDa pentaspan membrane glycoprotein, and have not been able to
      detect any C-terminally truncated form of rat prominin.

PMID- 11467843
TI  - Structural analyses of the UTF1 gene encoding a transcriptional coactivator
      expressed in pluripotent embryonic stem cells.
AB  - The UTF1 is a transcriptional coactivator expressed mainly in pluripotent
      embryonic stem cells. Here, we have isolated a genomic DNA fragment carrying the
      UTF1 gene and found that the gene contains two exons interrupted by a short
      intron. The gene possesses four GC boxes, but no TATA box in the 5'-flanking
      region. This is reminiscent of a housekeeping gene type promoter and the
      functional relevance of these motifs is confirmed by the transient transfection
      analyses. As to the gene product, our analyses have led to the identification of
      two different species. One of them corresponds to the full-length protein, while
      the other is produced by utilizing the second methionine codon for the
      translation initiation. The oligo-capping analyses reveal multiple transcription
      start sites. Interestingly, some of them are localized downstream of the first
      methionine codon, indicating that such transcripts produce a protein starting
      from the second methionine codon. Chromosomal mapping analyses locate the gene at
      7F5, the syntenic region of the human chromosome (10q26) where the human UTF1
      gene is located.

PMID- 11467844
TI  - Role of PI3-kinase in isoproterenol and IGF-1 induced ecNOS activity.
AB  - Phosphatidylinositol 3-kinase (PI3-K) has been shown to mediate insulin and
      insulin-like growth factor-1 (IGF-1)-induced nitric oxide (NO) generation and,
      thus, vascular tone. A role for PI3-K in G-protein-coupled receptor signal
      transduction has been reported. As beta (beta2)-adrenergic vascular actions are
      partly dependent on NO, we have investigated the role of PI3-K in isoproterenol
      (Iso) and IGF-1 induced endothelial NO synthase (ecNOS) activity in rat aortic
      endothelial cells (RAEC). Cell lysates of RAEC, exposed to Iso (10 micromol/L)
      for 5 min and 6 h, and to IGF-1 (100 nM) for 10 min and 6 h, or pretreated with
      PI3-K inhibitor Wortmannin (WT), were used for measuring PI3-K activity, p85kDa
      regulatory protein, and citrulline production. Results show that Iso and IGF-1
      increased a p85 subunit and citrulline production, and also enhanced 32P
      incorporation into PIP3. Pretreatment with WT inhibited Iso-stimulated ecNOS, as
      well as, PI3-K activity. Iso enhanced association of ecNOS with the triton X-100
      insoluble fraction of RAEC. These data indicate that the endothelial cell PI3-K
      pathway mediates, in part, the release of NO and subsequent vasorelaxation in
      response to this beta-agonist, as well as, IGF-1.

PMID- 11467845
TI  - Zinc binding to Alzheimer's Abeta(1-16) peptide results in stable soluble
      complex.
AB  - Aggregation of the human amyloid beta-peptide (Abeta) into insoluble plaques is a
      key event in Alzheimer's disease. Zinc sharply accelerates the Abeta aggregation
      in vitro, and the Abeta region 6-28 was suggested to be the obligatory zinc
      binding site. However, time-dependent aggregation of the zinc-bound Abeta species
      investigated so far prevented their structural analysis. By using CD
      spectroscopy, we have shown here for the first time that (i) the protected
      synthetic peptide spanning the fragment 1-16 of Abeta binds specifically zinc
      with 1:1 and 1:2 stoichiometry under physiologically relevant conditions; (ii)
      the peptide-zinc complex is soluble and stable for several months; (iii) zinc
      binding causes a conformational change of the peptide towards a more structured
      state. These findings suggest the region 1-16 to be the minimal autonomous zinc
      binding domain of Abeta.

PMID- 11467846
TI  - Development and characterization of cholinephosphotransferase antibody.
AB  - In the present study, we generated antibodies in rabbits against two synthetic
      peptides, one based on peptide sequence from yeast CPT cDNA (position 86 to 98 of
      the amino acid sequence) and the other from our guinea pig CPT cDNA (it
      corresponds to amino acid positions 119 to 130 according to yeast CPT gene). The
      antibody titers were measured by both dot blot analysis and ELISA using Keyhole
      limpets hemocyanin coupled CPT peptides. The CPT antibody recognized a single
      band by Western blot analysis of proteins from guinea pig liver mitochondria and
      microsomes. The molecular weight of the protein recognized by Western blot
      analysis is close to the predicted molecular weight (46 kDa) of yeast CPT.
      Further analysis revealed that the antibody inhibited CPT activity in both
      subcellular fractions in a dose dependent manner, thus confirming the specificity
      of the antibody against both subcellular CPT.

PMID- 11467847
TI  - Transcriptional activation of the nuclear receptor corepressor RIP140 by retinoic
      acid: a potential negative-feedback regulatory mechanism.
AB  - Through the use of microarray analysis it was discovered that the nuclear
      receptor coregulator, receptor interacting protein 140 (RIP140), was induced
      early during all-trans retinoic acid (RA)-induced differentiation of human
      embryonal carcinoma cells. A rapid, fourfold induction of RIP140 mRNA was
      detected within 3 h of RA treatment in human embryonal carcinoma and MCF-7 human
      breast cancer cells. RIP140 protein levels were induced within 6 h of RA
      treatment. The RA induction of RIP140 mRNA did not require de novo protein
      synthesis, consistent with RIP140 being a direct transcriptional target of
      retinoid receptors. Promoter/enhancer elements directly upstream of the RIP140
      coding region supported RA-induced transcription of a luciferase gene. In
      addition the ability of overexpressed RIP140 to repress ligand activated retinoid
      receptors was confirmed. The finding that RIP140 is a direct transcriptional
      target of RA is one of the first examples of acute transcriptional regulation of
      a nuclear receptor coactivator or corepressor. These data are consistent with a
      model by which RA induction of RIP140 supplies a negative feedback signal toward
      ligand-activated retinoid receptors.

PMID- 11467848
TI  - An investigation into the membrane-interactive potential of the Escherichia coli
      KpsE C-terminus.
AB  - Membrane binding via C-terminal amphiphilic alpha-helical structure is a novel
      anchoring mechanism, which has been characterised in a number of prokaryotic
      carboxypeptidases. Here, we have used graphical and DWIH analyses to ascertain if
      a similar anchoring mechanism may be utilised by the Escherichia coli KpsE
      protein in its binding to the periplasmic face of the inner membrane. The results
      of these analyses have been compared to those obtained for similar analyses of
      the C-terminal sequences of E. coli penicillin-binding proteins (PBPs) PBP5 and
      PBP6 which, are known to function as amphiphilic alpha-helical membrane anchors,
      and of melittin, a known membrane-interactive toxin. We have also used FTIR
      spectroscopy and lipid phase transition temperature analysis to investigate the
      interaction of a peptide homologue of KpsE C-terminal region with membrane lipid.
      Our results suggest that the KpsE C-terminal sequence has the potential to form
      an amphiphilic alpha-helix and that this alpha-helix could feature in the
      membrane binding of the protein.

PMID- 11467849
TI  - Identification of DNA-protein interactions in the 5' flanking and 5' untranslated
      regions of the human multidrug resistance protein (MRP1) gene: evaluation of a
      putative antioxidant response element/AP-1 binding site.
AB  - Overexpression of the multidrug resistance protein, MRP1, confers resistance to
      multiple natural product-type chemotherapeutics. MRP1 amplification is observed
      in some multidrug-resistant cell lines, while in others, increased transcription
      occurs in the absence of gene amplification. To investigate mechanisms
      influencing MRP1 transcription, three small cell lung cancer cell lines were
      examined: drug sensitive H69 cells with two apparently normal MRP1 alleles,
      highly resistant H69AR cells in which MRP1 is amplified and low level resistant
      H69PR cells that contain only one MRP1 allele. Deoxyribonuclease I footprinting
      and gel mobility shift assays were undertaken using nuclear extracts from the
      three cell lines and a 1 kb region encompassing the 5' flanking region of MRP1.
      Thirteen protein binding sites were identified of which six were sequence
      specific. Differences in levels of protein binding occurred with a putative
      antioxidant response element (ARE)/AP-1 binding site at -511 to -477. Levels of
      protein binding to this site were 2.5- to 3.0-fold higher in H69AR nuclear
      extracts versus extracts from H69 or H69PR cells. The AP-1 sequence is required
      for binding and c-Jun and JunD were identified as components of the protein
      complex. The ARE/AP-1 element functioned as a transcriptional enhancer but did
      not mediate induction of a luciferase reporter gene upon beta-naphthoflavone
      treatment.

PMID- 11467850
TI  - Inhibitory effect of copper(II) on zinc(II)-induced aggregation of amyloid beta
      peptide.
AB  - Aggregation of amyloid beta-peptide (Abeta), a key pathological event in
      Alzheimer's disease, has been shown in vitro to be profoundly promoted by Zn(II).
      This fact suggests that some factors in the normal brain protect Abeta from the
      Zn(II)-induced aggregation. We demonstrate for the first time that Cu(II)
      effectively inhibits the Abeta aggregation by competing with Zn(II) for histidine
      residues. The Raman spectrum of a metal-Abeta complex in the presence of both
      Zn(II) and Cu(II) shows that the cross-linking of Abeta through binding of Zn(II)
      to the N(tau) atom of histidine is prevented by chelation of Cu(II) by the N(pi)
      atom of histidine and nearby amide nitrogens. The inhibitory effect is strongest
      at a Cu/Abeta molar ratio of around 4. Above this ratio, Cu(II) itself promotes
      the Abeta aggregation by binding to the phenolate oxygen of Tyr10. These results
      emphasize the importance of regulation of Cu(II) levels to inhibit Abeta
      aggregation, and are consistent with an altered metal homeostasis in Alzheimer's
      disease.

PMID- 11467851
TI  - Protein kinase C epsilon suppresses Abeta production and promotes activation of
      alpha-secretase.
AB  - Deposition of plaques containing Abeta is considered important in the
      pathogenesis of Alzheimer's disease. Phorbol esters that activate protein kinase
      C (PKC) promote alpha-secretase-mediated processing of the beta amyloid precursor
      protein (APP), which generally reduces formation of Abeta. To determine which PKC
      isozymes mediate this process, we studied CHO cells that express human APP751.
      Phorbol 12-myristate, 13-acetate (PMA)-stimulated APP secretion, which was
      reduced by a general PKC inhibitor bisindoylmaleimide I, but not by Go 6976,
      which inhibits PKCalpha, beta, gamma, and mu. Since PKCdelta and epsilon were the
      only other PMA-sensitive isozymes present, we studied cells that express
      selective peptide inhibitors of these isozymes. Expression of the PKCepsilon
      inhibitor inhibited PMA-induced APPs secretion and suppression of Abeta
      production. In contrast, the PKCdelta inhibitor had no effect. These results
      provide evidence that PKCepsilon decreases Abeta production by promoting alpha
      secretase mediated cleavage of APP.

PMID- 11467852
TI  - Activity-dependent neural tissue oxidation emits intrinsic ultraweak photons.
AB  - Living organisms have been known to spontaneously emit ultraweak photons in vivo
      and in vitro. Origin of the photon emission remains unclear, especially in the
      nervous system. The spontaneous ultraweak photon emission was detected here from
      cultured rat cerebellar granule neurons using a photomultiplier tube which was
      highly sensitive to visible light. The photon emission was facilitated by the
      membrane depolarization of neurons by a high concentration of K+ and was
      attenuated by application of tetrodotoxin or removal of extracellular Ca2+,
      indicating the photon emission depending on the neuronal activity and likely on
      the cellular metabolism. Furthermore, almost all the photon emission was arrested
      by 2,4-dinitrophenylhydrazine, indicating that the photon emission would be
      derived from oxidized molecules. Detection of the spontaneous ultraweak photon
      emission will realize noninvasive and real-time monitoring of the redox state of
      neural tissue corresponding to the neuronal activity and metabolism.

PMID- 11467853
TI  - 25-hydroxy-vitamin d metabolism in human colon cancer cells during tumor
      progression.
AB  - RT-PCR analysis showed elevated expression of 25-hydroxyvitamin D-1alpha
      hydroxylase (1alpha-OHase) and of 25-hydroxyvitamin D-24-hydroxylase (24-OHase)
      in well differentiated human colon carcinomas in comparison to normal mucosa.
      Further tumor progression is associated with a rise in 1alpha-OHase but with no
      significant change in 24-OHase mRNA expression. Accordingly, HPLC analysis of 25
      hydroxy-vitamin D3 metabolism in freshly isolated tumor cells indicated that well
      to moderately differentiated colon cancers in situ are able to produce 1alpha,25
      dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and convert it through 24-OHase activity
      into side-chain modified metabolites, 1,24,25-(OH)3-D3 and 1,25-(OH)2- 24-oxo-D3.
      Likewise, 25-(OH)-D3 is metabolized into 24,25-(OH)2D3, 23,25-(OH)2D3, and 23,25
      (OH)2-24-oxo-D3. Poorly-differentiated cancers expressed low levels of 1alpha
      OHase mRNA, whereas 24-OHase was even over-expressed. RT-PCR and HPLC analysis of
      vitamin D metabolism in primary culture cell clones strongly suggested that the
      extent of endogenously produced 1alpha,25-(OH)2-D3 was inversely related to 24
      OHase activity, which could thus limit the antimitotic efficacy of 1alpha,25
      (OH)2-D3 particularly at late stages of colon cancer progression.

PMID- 11467854
TI  - Novel bifunctional alkaline protease inhibitor: protease inhibitory activity as
      the biochemical basis of antifungal activity.
AB  - An alkaline protease inhibitor (API) from a Streptomyces sp. NCIM 5127 was shown
      to possess antifungal activity against several phytopathogenic fungi besides its
      antiproteolytic (anti-feedent) activity [J. V. Vernekar et al. (1999) Biochem.
      Biophys. Res. Commun. 262, 702-707]. Based on the correlation between
      antiproteolytic and antifungal activities in several tests such as
      copurification, heat inactivation, chemical modification, and its binding
      interaction with the fungal protease, we demonstrate, for the first time, that
      the dual function of API is a consequence of its ability to inhibit the essential
      alkaline protease. The parallel enrichment of both the functions during
      purification together with the heat inactivation of API leading to the
      concomitant loss of the two activities suggested their presence on a single
      molecule. Chemical modification of API with NBS resulted in the complete loss of
      antiproteolytic and antifungal activities, with no gross change in conformation
      implying the involvement of a Trp residue in the active site of the inhibitor and
      the presence of a single active site for the two activities. Treatment of API
      with DTT abolished both the activities although the native structure of API
      remained virtually unaffected, indicating the catalytic role of the disulfide
      bonds. Inactivation of API either by active site modification or by
      conformational changes leads to the concurrent loss of both the antiproteolytic
      and antifungal activities. Experimental evidences presented here serve to
      implicate that the antifungal activity of API is a consequence of its protease
      inhibitory activity.

PMID- 11467855
TI  - Enhanced expression of the recombinant lethal factor of Bacillus anthracis by Fed
      Batch culture.
AB  - High cell density cultivation has been one of the most effective ways to increase
      cell as well as the product yields. The structural gene for the 90-kDa lethal
      factor (LF) isolated from Bacillus anthracis was expressed as fusion protein with
      6x histidine residues under the transcriptional regulation of the T5 promoter in
      Escherichia coli. Various strategies were tried to scale up the expression of the
      recombinant lethal factor by bioprocess optimization using fed batch culture
      technique in a 14 litre fermentor. The media, a defined mixture of salts, trace
      elements, vitamins, etc. along with a specified carbon source was used for the
      growth. The pH of the media was maintained at 6.8 while the temperature was
      changed from 37 to 28 degrees C during the cultivation. During the growth and
      induction phases, the DO was maintained above 20% by automatic control of
      agitation. The specific growth rate was controlled by utilizing an exponential
      feeding profile determined from mass balance equations. As a result of control of
      specific growth rate at two different levels, there was about twenty five fold
      increase in biomass compared to the biomass in the shake flask. E. coli cells
      yielded a soluble cytosolic protein with an apparent molecular mass of 90 kDa.
      The protein was purified to homogeneity using metal chelate affinity
      chromatography, followed by anion exchange on FPLC using Mono-Q column. In
      solution, trypsin cleaved protective antigen bound to native and recombinant LF
      with comparable affinity. The recombinant LF resembled the LF purified from B.
      anthracis in the macrophage lysis assay, using a murine macrophage cell line
      J774A.1 sensitive to anthrax toxin. It was possible to achieve a yield of 50 mg
      of the purified protein from 1 litre culture broth.

PMID- 11467856
TI  - Nonuniform quadriceps O2 consumption revealed by near infrared multipoint
      measurements.
AB  - Single location muscle monitoring does not reflect the heterogeneous activation
      of the muscle group(s) during a given exercise. Vastus lateralis and rectus
      femoris O2 consumption (VO2) was investigated, noninvasively, at rest and during
      maximal voluntary contractions (MVC) using a 12-channel near-infrared continuous
      wave spectroscopy (NIR(CWS)) system (0.1 s acquisition time). VO2 either at rest
      or during MVC was found to be nonuniform in the 11 out of 12 measurement sites
      over a surface of 8 x 8 cm2. As expected, VO2 during exercise was significantly
      higher than VO2 at rest (P < 0.01). However, at each muscle measurement site no
      difference was found between the mean values (n = 12) of VO2 measured during a 5
      s intermittent MVC and the VO2 values measured during 30-s continuous MVC (P =
      0.25). These results strengthen the role of NIR(CWS) as a powerful tool for
      investigating the spatial and temporal features of muscle oxygenation changes as
      well as muscle VO2.

PMID- 11467857
TI  - Identification of human CPI-17, an inhibitory phosphoprotein for myosin
      phosphatase.
AB  - CPI-17 is a phosphorylation-dependent inhibitor of myosin phosphatase. cDNA
      clones encoding CPI-17 were isolated from a human aorta library. Overlapping
      clones indicated two isoforms: CPI-17alpha was 147 residues and mass of 16.7 kDa;
      CPI-17beta (120 residues, mass 13.5 kDa) resulted from a deletion in the alpha
      isoform of 27 residues, sequence 68-94. N-terminal 67 residues of all CPI-17
      isoforms (human, porcine, rat and mouse) were highly conserved (for the human and
      porcine isoforms the identity was 91%). The presence of the two human isoforms
      was detected from cDNA sequences amplified by RT-PCR and by Western blots on
      human aorta. The cloned human CPI-17 gene indicated 4 coding exons and CPI-17beta
      was an alternative splice variant due to deletion of the second exon. FISH
      analysis located the human CPI-17 gene on chromosome 19q13.1.

PMID- 11467858
TI  - Structure-activity analysis of SMAP-29, a sheep leukocytes-derived antimicrobial
      peptide.
AB  - SAMP-29 is a cathelecidin-derived antimicrobial peptide deduced from sheep
      myeloid mRNA. To elucidate the structural-activity relationship of SMAP-29,
      several analogues were synthesized and their antibiotic activity was
      investigated. Compared to parental SMAP-29, SMAP-29(1-17) and [K(22,25,27)]-SMAP
      29 retained relatively effective antimicrobial activity (MIC: 1.0-8.0 microM),
      but resulted in a complete loss of hemolytic activity. Pro-19 --> Ala
      substitution ([A19]-SMAP-29) in SMAP-29 induced a significant reduction in
      antibacterial activity. These results suggested that the N-terminal amphipathic
      alpha-helical region and the C-terminal hydrophobic region of SMAP-29 are
      responsible for antimicrobial activity and hemolytic activity, respectively, and
      the central Pro-19 in SMAP-29 plays a critical role in showing improved
      antibacterial activity. In particular, [K(2,7,13)]-SMAP-29(1-17) showed potent
      antimicrobial activity under high salt conditions without hemolytic activity.
      Thus, this short peptide could serve as an attractive candidate for the
      development of therapeutic antimicrobial drugs. Structural analysis by circular
      dichroism suggested that SMAP-29 seems to adopt a helix-bend/turn-extended random
      conformation.

PMID- 11467859
TI  - Purification of a heterodimeric betaine aldehyde dehydrogenase from wild amaranth
      plants subjected to water deficit.
AB  - Betaine aldehyde dehydrogenase was purified to homogeneity from wild-type
      amaranth plants subjected to water deficit. The enzyme has a native molecular
      mass of 125 kDa; it is formed by two subunits, one of the subunits with a
      molecular mass of 63 kDa and the second one of 70 kDa as determined by SDS-PAGE
      and double dimension electrophoresis. IEF studies showed two bands with pI values
      of 4.93 and 4.85, respectively. Possible glycosilation of the 63- and 70-kDa
      subunits were tested with negative results. Both subunits cross-reacted strongly
      with polyclonal antibody raised against porcine kidney BADH. Also antiserum rose
      against HSP70 cross-reacted strongly with the wild amaranth BADH 70-kDa subunit.
      The enzyme was stable to extreme pH's and temperatures, and high KCl
      concentrations. Product inhibition of BADH was not observed.

PMID- 11467860
TI  - Expression of renin-angiotensin system genes in immature and mature dendritic
      cells identified using human cDNA microarray.
AB  - Using a cDNA glass microarray, the expression of 1081 genes in immature and
      mature dendritic cells (DCs) of two different individuals has been studied. The
      upregulation of mRNA transcripts of genes encoding the transcription factor ZFM1,
      Mos proto-oncogene serine/threonine-protein kinase, B-cell-specific transcription
      factor, preB-cell growth stimulating factor, ets translocation variant 6, and
      epidermal growth-factor-like CRIPTO was for the first time detected in DCs. Using
      semiquantitative RT-PCR analysis the upregulation of the transforming growth
      factor-alpha, integrin alpha 6 and ZFM 1 transcription factor in mature DCs was
      confirmed in samples from four different individuals. On the other hand, the
      downregulation of renin-binding protein transcript was detected in mature DCs
      using a cDNA microarray. For the first time, the expression of renin-angiotensin
      system genes was evaluated during maturation of DCs in samples from four donors
      by semiquantitative RT-PCR. A possible role of the renin-angiotensin system in
      DCs is discussed.

PMID- 11467861
TI  - Dissociation of 5' AMP-activated protein kinase activation and glucose uptake
      stimulation by mitochondrial uncoupling and hyperosmolar stress: differential
      sensitivities to intracellular Ca2+ and protein kinase C inhibition.
AB  - 2,4-dinitrophenol (DNP) compromises ATP production within the cell by disrupting
      the mitochondrial electron transport chain. The resulting loss of ATP leads to an
      increase in glucose uptake for anaerobic generation of ATP. In L6 skeletal muscle
      cells, DNP increases the rate of glucose uptake by twofold. We previously showed
      that DNP increases cell surface levels of glucose transporter 4 (GLUT4) and
      hexose uptake via a Ca2+-sensitive and conventional protein kinase C (cPKC)
      dependent mechanism. Recently, 5' AMP-activated protein kinase (AMPK) has been
      proposed to mediate the stimulation of glucose uptake by energy stressors such as
      exercise and hypoxia. Changes in Ca2+ and cPKC have also been invoked in the
      stimulation of glucose uptake by exercise and hypoxia. Here we examine whether
      changes in cytosolic Ca2+ or cPKC lead to activation of AMPK. We show that
      treatment of L6 cells with DNP (0.5 mM) or hyperosmolar stress (mannitol, 0.6 M)
      increased AMPK activity by 3.5-fold. AMPK activation peaked by 10-15 min prior to
      maximal stimulation of glucose uptake. Intracellular Ca2+ chelation and cPKC
      inhibition prior to treatment with DNP and hyperosmolarity significantly reduced
      cell surface GLUT4 levels and hexose uptake but had no effect on AMPK activation.
      These results illustrate a break in the relationship between AMPK activation and
      glucose uptake in skeletal muscle cells. Activation of AMPK does not suffice to
      stimulate glucose uptake in response to DNP and hyperosmolarity.

PMID- 11467862
TI  - Hypsin, a novel thermostable ribosome-inactivating protein with antifungal and
      antiproliferative activities from fruiting bodies of the edible mushroom
      Hypsizigus marmoreus.
AB  - A novel ribosome-inactivating protein with a molecular weight of 20 kDa was
      isolated from fruiting bodies of the mushroom Hypsizigus marmoreus. The isolation
      procedure entailed ion exchange chromatography on CM-cellulose, affinity
      chromatography on Affi-gel Blue Gel and ion exchange chromatography on Mono Q.
      The protein designated hypsin demonstrated an inhibitory action against mycelial
      growth in various fungal species including Mycosphaerella arachidicola,
      Physalospora piricola, Fusarium oxysporum, and Botrytis cinerea with an IC50 of
      2.7, 2.5, 14.2, and 0.06 microM, respectively. Translation in the rabbit
      reticulocyte lysate system was inhibited with an IC50 of 7 nM and HIV-1 reverse
      transcriptase activity was inhibited with an IC50 of 8 microM. Antiproliferative
      activity against mouse leukemia cells and human leukemia and hepatoma cells was
      observed. About 60% of the translation-inhibitory activity was retained after
      heating at 100 degrees C for 10 min. No loss of translation-inhibitory activity
      occurred after brief treatment with trypsin.

PMID- 11467863
TI  - Dynamic contrast-enhanced MRI studies in oncology with an emphasis on
      quantification, validation and human studies.
AB  - Magnetic resonance imaging (MRI), after the administration of an extracellular,
      gadolinium-based contrast medium, can be used to detect and characterize human
      tumours. The success of dynamic contrast-enhanced MRI (DCE-MRI) is dependent on
      its ability to demonstrate intrinsic differences between a variety of tissues
      that affect contrast medium behaviour. Evidence is mounting that DCE-MRI
      measurements correlate with immunohistochemical surrogates of tumour
      angiogenesis. DCE-MRI can monitor the effectiveness of a variety of treatments
      including chemotherapy, hormonal manipulation, radiotherapy and novel therapeutic
      approaches including antiangiogenic drugs. Kinetic parameters in the treatment
      setting have been correlated with histopathological outcome and patient survival.
      This article reviews quantification analysis of these studies together with
      current and future clinical applications.

PMID- 11467864
TI  - Primary and metastatic lobular carcinoma of the breast.
AB  - Invasive lobular carcinoma of the breast is the second most common type of
      primary breast cancer, accounting for 8-14% of cases, but is often difficult to
      diagnose early. It typically shows a diffuse pattern of infiltration within the
      breast, resulting in a variety of often subtle radiological appearances. A
      similar infiltrative pattern is seen in its metastatic form, with involvement of
      the gastrointestinal tract, peritoneum, retroperitoneum, bone marrow, meninges
      and uterus occurring more frequently than with the more common infiltrating
      ductal carcinoma of the breast. This pictorial essay illustrates the spectrum of
      radiological appearances which may be encountered with both primary and secondary
      lobular carcinoma.

PMID- 11467865
TI  - MR imaging of children's knees.
AB  - The spectrum of paediatric knee disorders ranges from developmental and growth
      disorders, traumatic derangement, inflammation, infection, and diffuse marrow
      disorder to neoplasm. We present in this pictorial review the MR imaging findings
      used to characterize these various diseases affecting the knee region of children
      and adolescents.

PMID- 11467866
TI  - Magnetic resonance and cranial ultrasound characteristics of periventricular
      white matter abnormalities in newborn infants.
AB  - OBJECTIVE: To characterize the range of abnormalities within the periventricular
      white matter (PVWM) in a cohort of newborns using magnetic resonance (MR) brain
      imaging and to compare the focal MR abnormalities with the cranial ultrasound
      (CUS) findings. METHODS: Retrospective study of MR brain and CUS findings of
      infants born in the 18-month period 1998-1999. PVWM abnormalities were identified
      by MR and focal lesions were characterized by size, number and distribution using
      a grading scale. Correspondence with CUS findings was assessed. RESULTS: 175 MR
      examinations corresponding to n = 105 preterm infants, (median GA 28, range 23-36
      weeks) and n = 25 term infants (median GA 39, range 37-42 weeks) were analysed
      for PVWM abnormalities. In the preterm group, MR demonstrated a normal PVWM in n
      = 76, focal areas of altered signal intensity (SI) in PVWM in n = 26 and venous
      infarction in n = 3. In the term group, MR demonstrated a normal PVWM in n = 15,
      focal areas of altered SI in PVWM in n = 4, oedematous PVWM in n = 2 and a middle
      cerebral artery infarction in n = 4. All infants with normal MR had normal CUS
      findings. A focal PVWM SI abnormality detectable on MR corresponded with an
      abnormality on CUS in only n = 10/30. CONCLUSIONS: MR appears considerably more
      sensitive than CUS in demonstrating the existence and extent of focal PVWM
      lesions in newborn infants. Satisfactory correspondence between the two imaging
      investigations is obtained only for cystic PVWM lesions.

PMID- 11467867
TI  - Magnetization transfer MR imaging correlation with histopathology in intracranial
      tuberculomas.
AB  - OBJECTIVE: The purpose of this study was to correlate the differences in the
      magnetization transfer (MT) ratios of different components of the tuberculoma
      with histopathology and to see whether MT or conventional MR imaging correlates
      better with histopathology. METHODS: MT T1 and conventional spin echo MR imaging
      was performed in six patients with intracranial tuberculomas. The tuberculomas
      were excised as a single mass and ex vivo MR imaging was performed using the same
      protocol. The gross histopathology was compared with in vivo imaging with respect
      to the MR signal intensity (MT ratio) in all six specimens. RESULTS: The size of
      the tuberculomas was larger on MT T1-weighted images compared to T2-weighted
      images and matched the gross measurements of each specimen. The MT hyperintense
      rim matched the cellular component of the tuberculoma that was masked on T2
      weighted images because of the associated perifocal oedema. The cellular
      component had a lower MT ratio compared to the necrotic components. CONCLUSION:
      The outer hyperintense rim and hyperintense strands are due to the cellular
      infiltrate, noncaseating granulomas, and gliosis while the hypointense core
      represents solid caseation. The cellular outer rim shows lower MT ratio compared
      to the core of the tuberculoma. Histological correlation of the cellular and
      necrotic components of tuberculomas is best shown with MT T1 imaging.

PMID- 11467868
TI  - HTLV-1-associated bronchopneumonopathy (HAB): CT-pathological correlation.
AB  - We describe the thin-section CT appearances of HTLV-1-associated
      bronchopneumonopathy, with histopathological correlation, in two biopsy proven
      cases.

PMID- 11467869
TI  - Hand fractures: a study of their site and type in childhood.
AB  - AIM: The purpose of the study was to document the site and type of fractures of
      the hand in children up to 16 years of age. MATERIALS AND METHODS: The
      radiographs of 280 children who were found to have a fracture in Accident and
      Emergency over a one-year period were reviewed. A total of 293 fractures of the
      hand and 3 distal interphalangeal joint dislocations without fracture were
      identified. There were 293 fractures as some children had more than one fracture.
      RESULTS: Distal tuft fractures were commonest in the 0 to 4-year age-group;
      fractures of distal phalanx (both transverse and tuft) in the 5 to 8-year age
      group; transverse fractures of the proximal phalanx of little finger in the 9 to
      12-year age-group and transverse fractures of neck of the fifth metacarpal in the
      13 to 16-year age-groups. CONCLUSION: Hand fractures are more common in older
      children, with a male preponderance in most groups except in the 0-4 age-group.
      The site of injury is different in the various corresponding age-groups,
      reflecting the differing mechanisms of injury. The management of hand fractures
      rely on a correct diagnosis and a knowledge of their common site in each age
      group should aid diagnosis.

PMID- 11467870
TI  - The use of dilute Calogen as a fat density oral contrast medium in upper
      abdominal computed tomography, compared with the use of water and positive oral
      contrast media.
AB  - AIM: Oral contrast media are commonly given prior to computed tomography (CT)
      examination of the upper abdomen. Although positive oral contrast media are
      normally used, there is increasing interest in using negative agents such as
      water and less commonly fat density products. The aim of this study was to
      compare a positive oral contrast medium, water, and a diluted emulsion of arachis
      oil Calogen, a fat density food supplement) for assessment of the upper abdomen.
      MATERIALS AND METHODS: Seventy-one patients referred for upper abdominal CT were
      randomized to receive either 500 ml water, 2% sodium diatrizoate or a dilute
      suspension of Calogen. The CT images were scored independently by three
      radiologists. Distension and anatomical identification was assessed for the
      stomach, duodenum and jejunum; with anatomical identification recorded for the
      pancreas, retroperitoneum, liver, gallbladder and spleen. RESULTS: Dilute Calogen
      produced a significant improvement (P < 0.01) in distension and anatomical
      visualization of the stomach and proximal duodenum. Only minimal differences were
      demonstrated between the three contrast media for visualization of more distal
      small bowel or identification of the other upper abdominal viscera. Significantly
      more artifacts were caused by positive contrast media than with the Calogen
      mixture. CONCLUSION: A dilute suspension of Calogen as an oral contrast medium is
      recommended when disease is suspected within the stomach or proximal duodenum.

PMID- 11467871
TI  - Diffuse mesenteric and omental infiltration by amyloidosis with omental
      calcification mimicking abdominal carcinomatosis.

PMID- 11467872
TI  - Screwdriver headache: a case of traumatic intracranial hypotension.

PMID- 11467873
TI  - Mucormycosis of rectum - computed tomography findings.

PMID- 11467874
TI  - Adrenal histoplasmosis manifested as Addison's disease: unusual CT features with
      magnetic resonance imaging correlation.

PMID- 11467875
TI  - Ovarian lymphangioma: MRI appearances.

PMID- 11467876
TI  - Bowel opacification due to cleansing agent?

PMID- 11467878
TI  - D-dimer assay for deep vein thrombosis. its role with colour Doppler sonography.

PMID- 11467879
TI  - Patterns of testosterone and prolactin concentrations and reproductive behavior
      of helpers and breeders in the cooperatively breeding red-cockaded woodpecker
      (Picoides borealis).
AB  - We examined the proximate causes of delayed breeding and alloparental behavior in
      the cooperatively breeding red-cockaded woodpecker by measuring plasma
      concentrations of testosterone (T) and prolactin (PRL) in female breeders, male
      breeders, and male helpers during different stages of the reproductive cycle.
      Male breeders and helpers have low T during the prebreeding period, highest T
      during copulation, and low concentrations of T during the egg-laying/incubation
      and nestling provisioning stages. Helpers appear physiologically capable of
      reproducing; their T concentrations equal that of male breeders. Helpers
      unrelated to the breeding female have higher T than helpers sharing a territory
      with their mother. Sexual inactivity by male helpers might be explained by
      behavioral suppression resulting from interactions of male helpers with the
      breeding pair that somehow differ in accordance with the helper's relatedness to
      the breeding female (e.g., female breeders are generally unreceptive to courtship
      from male helpers and least receptive to related helpers). Female breeder, male
      breeder, and male helper PRL levels did not differ and increased from the
      prebreeding stage through the copulation and egg-laying/incubation stages. During
      the nestling provisioning stage, male breeder and helper PRL declined, while
      female PRL continued to increase. Based on these results, we conclude that the
      physiological bases of alloparental behavior have not diverged from those that
      mediate parental behavior in this species.

PMID- 11467880
TI  - Hormonal correlates of siblicide in Galapagos Nazca boobies.
AB  - Nazca boobies (Sula granti) show unconditional obligate siblicide immediately
      after hatching, reducing the typical two-egg clutch size to one. We studied body
      mass changes and levels of testosterone (T), corticosterone (CORT), and
      progesterone (P) for A-chicks (dominant, first hatched), B-chicks (subordinate,
      second hatched), and singletons, during the first 7 days after hatching, when
      siblicide normally occurs. Mass increase with age was higher for A-chicks than
      for singletons and B-chicks. This exaggerated the existing developmental
      advantage of A- over B-chicks that is due to hatching asynchrony. In nests with
      two chicks, CORT titer was significantly higher in B-chicks than in A-chicks.
      During ontogenetic development, CORT decreased with age for A-chicks, but did not
      change for singletons. P showed qualitatively similar ontogenetic changes to
      CORT, remaining unchanged for A-chicks but increasing for singletons. Thus, both
      CORT and P levels were lower for A-chicks than for singletons, and both hormones
      varied inversely with body mass. Overall, T levels did not differ between
      different categories of chicks. However, one B-chick in the process of reversing
      the dominance relationship with its older, but weakened, sibling had
      significantly elevated T. We suggest that CORT and P are regulated to promote
      exaggerated mass gain in socially challenged A-chicks, facilitating siblicide.
      Whether T induces aggressiveness during short time intervals of intense sibling
      rivalry needs further attention.

PMID- 11467881
TI  - Manipulations of the AVT system shift social status and related courtship and
      aggressive behavior in the bluehead wrasse.
AB  - Arginine vasotocin (AVT) and its mammalian homologoue arginine vasopressin (AVP)
      influence male sexual and aggressive behaviors in many species. We tested the
      effects of AVT and an AVP-V(1a) receptor antagonist on the display of alternative
      male tactics in a tropical coral reef fish, the bluehead wrasse Thalassoma
      bifasciatum. We gave AVT injections to territorial and nonterritorial males of
      the large and colorful phenotype (terminal phase) and an AVP-V(1a) receptor
      antagonist, Manning compound, to territorial males in the field. AVT increased
      courtship independent of status, while its effects on territoriality and
      aggression were dependent upon male status. In territorial males, AVT increased
      courtship and tended to decrease the number of chases toward initial phase
      individuals. In nonterritorial males, AVT increased courtship, chases toward
      initial phase individuals, and territorial behavior while decreasing feeding.
      These are all behaviors rarely seen in nonterritorial males, so AVT made these
      males act like territorial TP males. The AVP-V(1a) receptor antagonist had
      opposite effects. It decreased courtship and territorial defense, making these
      males act more like nonterritorial males. Manipulations of the AVT system shifted
      males within a single phenotype from the nonterritorial social status to the
      territorial social status and vice versa. Since the entire suite of behaviors
      related to territoriality was affected by AVT system manipulations, our results
      suggest that the AVT system may play a key role in motivation of behaviors
      related to mating.

PMID- 11467882
TI  - Testosterone, paternal behavior, and aggression in the monogamous California
      mouse (Peromyscus californicus).
AB  - Testosterone (T) mediates a trade-off, or negative correlation, between paternal
      behavior and aggression in several seasonally breeding avian species. However,
      the presence or absence of a T-mediated trade-off in mammals has received less
      attention. We examined the relationship between paternal behavior and territorial
      aggression in the biparental California mouse, Peromyscus californicus. In
      contrast to seasonally breeding birds, T maintains paternal behavior in this year
      round territorial species. Castration reduced paternal behavior, whereas T
      replacement maintained high levels of paternal behavior. We hypothesize that T is
      aromatized in the brain to estradiol, which in turn stimulates paternal behavior.
      In contrast to paternal behavior, aggressive behavior was not reduced by
      castration. Interestingly, only sham males showed an increase in aggression
      across three aggression tests, while no change was detected in castrated or T
      replacement males. Overall, trade-offs between aggression and paternal behavior
      do not appear to occur in this species. Measures of paternal behavior and
      aggression in a correlational experiment were actually positively correlated. Our
      data suggest that it may be worth reexamining the role that T plays in regulating
      mammalian paternal behavior.

PMID- 11467883
TI  - Control of attractivity and receptivity in female red-sided garter snakes.
AB  - Female red-sided garter snakes emerge from their hibernacula in the spring
      attractive and receptive to males. Attractivity is communicated by a pheromone
      released through the female's skin and is a consequence of ovarian recrudescence
      the previous summer. Receptivity, on the other hand, is stimulated by ovarian
      estrogen secretion during emergence itself. Mating renders females both
      unattractive and unreceptive. Another "mating" pheromone of male origin is
      important in making females unattractive after mating. To investigate the role of
      cloacal stimulation in the loss of attractivity and receptivity we injected a
      local anesthetic (lidocaine or tetracaine) in the cloacal region of females
      before mating. This does not prevent mating, although it blocks neural
      transmission of copulatory sensory stimuli. The time course of transition from
      attractive and receptive states was then observed. Females treated with local
      anesthetic as well as control females were unattractive within 15 min of mating.
      However, when retested 2-3 and 24 h after mating, a significantly higher
      proportion of treated females regained their attractivity, while mated control
      females remained unattractive. This restorative effect was transient, though, as
      treated females retested 48 h after mating were as unattractive as the controls.
      Both anesthetized and control females were unreceptive when tested following
      mating and did not regain receptivity with time. Last, the mating-induced surge
      in circulating concentrations of prostaglandin was diminished in females that
      received a local anesthetic prior to mating. Taken together these results
      indicate that the loss of attractivity and receptivity following mating in the
      red-sided garter snake is due to combined effects of a mating pheromone and a
      physiological, neurally mediated response to the sensation of stimuli associated
      with the act of mating.

PMID- 11467884
TI  - Vasopressin and aggression in cross-fostered California mice (Peromyscus
      californicus) and white-footed mice (Peromyscus leucopus).
AB  - To examine how developmental experiences alter neural pathways associated with
      adult social behavior, we cross-fostered pups between the more aggressive and
      monogamous California mouse (Peromyscus californicus) and the less aggressive and
      polygamous white-footed mouse (P. leucopus). Cross-fostered males became more
      like their foster parents when tested as adults. Male white-footed mice became
      more aggressive only in an aggression test in a neutral arena, whereas the
      territorial California mice became less aggressive in resident-intruder
      aggression test, as measured by attack latency. Only the species that displayed a
      change in resident-intruder aggression showed a change in arginine vasopressin
      (AVP) levels: cross-fostered California mice had significantly lower levels of
      AVP-immunoreactive (AVP-ir) staining than controls in the bed nucleus of the
      stria terminalis (BNST) and the supraoptic nucleus (SON) and a nonsignificant
      trend toward lower levels in the medial amygdala (MA). Neither species showed
      changes in AVP-ir staining in a control area, the paraventricular nucleus (PVN).
      The changes in AVP-ir staining in the BNST and SON may not be caused by stress
      because cross-fostering was not associated with changes in adult plasma
      concentrations of two steroid hormones, corticosterone and testosterone, that
      have been associated with stress-related alterations in AVP pathways. These
      results suggest that manipulating the early parental environment can directly
      alter both a neurotransmitter system and species-typical patterns of social
      behavior, but that these effects may vary between species and under different
      social contexts.

PMID- 11467885
TI  - Effects of the phytoestrogen coumestrol on locomotor and fear-related behaviors
      in female mice.
AB  - Effects of the estrogenic plant isoflavonoid coumestrol (COUM) on locomotor
      activity and fear-related behaviors in both the absence and the presence of
      estradiol benzoate (EB) were examined in adult ovariectomized Swiss-Webster mice.
      In a running wheel paradigm conducted over 10 days, with treatment beginning 12
      days prior to testing, daily subcutaneous (sc) injections of 10 microg of COUM
      did not influence locomotor activity, whereas even the low dose of EB supplied by
      sc Silastic implant (2.5 microg lasting 5 weeks) produced a significant increase
      in locomotor activity over animals receiving vehicle alone. In animals receiving
      both COUM and EB, locomotor activity was significantly diminished compared to the
      activity observed in animals receiving EB alone. The same animals were also
      tested in three behavioral paradigms having known activity and fear components
      (open field, dark/light transition, elevated plus-maze). COUM did not produce
      significant effects in these assays. However, in an associative fear learning
      paradigm (fear conditioning), COUM produced significantly less freezing
      ("fearfulness") in the conditioned fear task than with animals receiving vehicle
      or a low dose of EB, which did not differ from each other. Unlike EB, which has
      comparable affinities for estrogen receptor (ER) alpha and ER beta, COUM has a
      higher affinity for ER beta than for ER alpha. COUM might disrupt estrogen
      enhanced locomotor activity by altering the dynamic by which EB acts on the brain
      through these two ER isoforms. The conditioned fear result suggests that COUM may
      produce additional effects through alternative pathways.

PMID- 11467886
TI  - Sensory cues mediating mating-induced potentiation of sexual receptivity in
      female rats.
AB  - Repeated mating of estradiol-primed female rats increases sexual receptivity. Two
      studies were conducted to determine the contribution of vaginal--cervical
      stimulation (VCS) to this increase. In the first study, female rats were
      repeatedly mated for 165 min. The vaginas of half of the females were covered
      with tape (masked) to prevent intromissions by the males. The remaining females
      were unmasked. Only females receiving intromissions (unmasked) showed a
      significant increase in sexual receptivity during repeated mating, suggesting
      that VCS from intromissions is necessary for repeated mating to increase sexual
      receptivity. In the second experiment, female rats received either experimentally
      administered VCS or control scapular stimulation administered with a plastic
      probe 1 h prior to testing for sexual receptivity. VCS applied in this manner
      significantly increased sexual receptivity. Together, these findings suggest that
      VCS from intromissions is one of the primary factors responsible for increases in
      sexual receptivity following repeated mating.

PMID- 11467887
TI  - Quantitative in situ correlation between microscopic MRI and polarized light
      microscopy studies of articular cartilage.
AB  - OBJECTIVE: To establish the correlation between the non-invasive imaging by
      magnetic resonance microscopy (microMRI) and the histological imaging by
      polarized light microscopy (PLM) accurately, quantitatively, at the highest
      possible MRI resolution (13.7 microm), and based on the same piece of tissue
      (articular cartilage from canine shoulder joint). DESIGN: In microMRI
      experiments, the laminar appearance (the magic angle effect) of the proton
      intensity images and the anisotropic characteristics of the T(2)relaxation images
      were analysed. In PLM experiments, the images of the optical retardation and
      collagen-fibre orientation in cartilage were constructed in two dimensions.
      RESULTS: The T(2)profile has a distinctly asymmetric bell-shaped curve and three
      featured zones. The retardation profile has a non-zero minimum at the middle of
      the transitional zone of the tissue. The angle profile has a smooth variation
      across the transitional zone. These facts suggest that the collagen fibres in the
      transitional zone are not entirely random but have a residual order. In addition,
      the peak of the T(2)profile coincides with the minimum of the retardation
      profile, both represent the most isotropic region of the tissue. A hyperbolic
      tangent function was found to best describe the transition of the collagen fibres
      in cartilage. A set of criteria was developed for each technique to define the
      features in the quantitative measurements. CONCLUSIONS: The criteria offer, for
      the first time, a set of quantitative and objective means to subdivide the tissue
      thickness into the zones in histology and in MRI. It is shown that the microMRI
      zones based on the T(2)characteristics are statistically equivalent to the
      histological zones based on the collagen fibre orientation (t-probabilities of
      0.730, 0.973, 0.647, 0.850 for the superficial, transitional, radial zones and
      the total thickness).

PMID- 11467888
TI  - Effects of non-steroidal antiinflammatory drugs and dexamethasone on the activity
      and expression of matrix metalloproteinase-1, matrix metalloproteinase-3 and
      tissue inhibitor of metalloproteinases-1 by bovine articular chondrocytes.
AB  - OBJECTIVE: To determine the in-vitro effects of several non-steroidal
      antiinflammatory drugs and the glucocorticoid dexamethasone on the IL-1 altered
      expression and activity of MMP-1, MMP-3 and TIMP-1 by bovine articular
      chondrocytes. DESIGN: Bovine chondrocytes were cultured in alginate gel beads.
      Cells were treated with IL-1alpha in the presence of vehicle or drugs at various
      concentrations. After 48 h mRNA expression of MMP-1, MMP-3, and of the tissue
      inhibitor of metalloproteinases (TIMP-1) was analysed by RT-PCR-ELISA. The
      protein synthesis of TIMP-1 and MMP-3 was determined by immunoprecipitation. The
      activity of enzymes and inhibitors was measured by functional assays. RESULTS: IL
      1 increased the expression and activity of MMPs. In contrast, TIMP activity
      remained unchanged although TIMP-1 expression was down-regulated. All tested
      NSAIDs and dexamethasone inhibited collagenase activity induced by IL-1.
      Transcript levels of MMP-1, however, were only reduced by indomethacin,
      meloxicam, naproxen and dexamethasone. Proteoglycanase activity was only reduced
      by indomethacin, meloxicam and dexamethasone. These effects were pre
      translational as confirmed by immunoprecipitation. The IL-1 decreased expression
      of TIMP-1 was further reduced by dexamethasone, which resulted in a significant
      loss of TIMP activity. No effects on TIMP activity or TIMP-1 biosynthesis were
      observed after treatment of chondrocytes with NSAIDs. CONCLUSION: Our studies
      clearly demonstrate that marked differences exist between individual NSAIDs with
      respect to their ability to modulate the imbalance between proteases and
      inhibitors during OA and RA, suggesting that the respective modes of action are
      independent of the inhibition of cyclooxygenases. Due to their co-regulation of
      MMPs and TIMP(s) glucocorticoids should be carefully studied for their overall
      effect on ECM proteolysis.

PMID- 11467889
TI  - Basic calcium phosphate crystals up-regulate metalloproteinases but down-regulate
      tissue inhibitor of metalloproteinase-1 and -2 in human fibroblasts.
AB  - OBJECTIVE: To examine the effect of basic calcium phosphate (BCP) crystals on
      expression of tissue inhibitors of metalloproteinases (TIMP)-1 and -2 in human
      fibroblasts. METHOD: Using a semi-quantitative reverse transcription-polymerase
      chain reaction method and phosphocitrate (PC), a specific inhibitor of the
      biological effects of BCP crystals, we examined the effects of BCP on the steady
      state transcript levels of metalloproteinase (MMP)-1, -3, -9 and -13 and TIMP-1
      and -2 in human fibroblasts. DNA primers against elongation factor were used as
      internal controls. RNAs isolated from human fibroblasts treated with BCP crystals
      (50 microg/ml) in the presence or absence of PC (10(-3) M) were used as
      templates, and RNA from untreated control cultures and cultures treated with
      Interleukin-1-beta (IL-1beta) were used as negative and positive controls,
      respectively. RESULTS: We observed increases in MMP-1, -3, -9 and -13 transcripts
      by BCP crystals. BCP crystal down-regulated TIMP-1 and -2 over untreated
      controls. Western blot analysis confirmed that BCP crystals down-regulate the
      synthesis of TIMP-1 and -2. While IL-1beta up-regulated MMP-1, -3, -9 and -13, it
      had no significant effect on expression of either TIMP. In all cases, PC
      specifically reversed the differential regulation of MMPs and TIMPs by BCP
      crystals but had no effect on IL-1beta induction of MMP expression. CONCLUSION:
      The ability of BCP to induce the synthesis of degradative MMPs while down
      regulating the synthesis of the naturally occurring counterpart TIMPs may explain
      the changes consistent with a role of BCP crystal in the pathogenesis of
      degenerative changes in osteoarthritis. The ability of PC to reverse both
      degradative effects of BCP crystal suggests that PC can be a potential
      therapeutic agent for BCP crystal deposition diseases.

PMID- 11467890
TI  - Expression of vitamin D receptors and matrix metalloproteinases in osteoarthritic
      cartilage and human articular chondrocytes in vitro.
AB  - OBJECTIVES: To examine the in situ distributions of vitamin D receptors (VDR) and
      matrix metalloproteinases (MMPs) in osteoarthritic cartilage for comparison with
      non-arthritic, normal cartilage; and to assess the in vitro effects of 1alpha,25
      dihydroxyvitaminD(3)(1alpha,25(OH)(2)D(3)) on MMPs-1, -3 and -9 and prostaglandin
      E(2)(PGE(2)) production by cultures of human articular chondrocytes (HAC) shown
      to be VDR-positive. METHODS: Using immunohistochemistry VDR expression in
      different specimens of osteoarthritic cartilage (N=11) was compared to that in
      normal cartilage (N=6), along with the immunodetection of MMPs-1, -3 and -9. The
      effects of 1alpha25(OH)(2)D(3)on MMP and PGE(2)production by HAC in vitro, with
      and without stimulation by TNFalpha or phorbol myristate acetate (PMA), was
      evaluated using ELISA methodology. RESULTS: VDR was demonstrated in HAC of all
      specimens of osteoarthritic cartilage, especially the superficial zone, whereas
      only two of five normal cartilage specimens were VDR(+)for a minor proportion of
      HAC. Immunolocalization of MMPs-1, -3 and -9 was often seen in areas where
      chondrocytes were VDR(+), and dual immunolocalization has demonstrated individual
      chondrocytes positive for both VDR and MMP-3 in situ. In vitro,
      1alpha25(OH)(2)D(3)alone had no effect on MMP-1, -9 and PGE(2)production by HAC,
      but MMP-3 production was up-regulated by 1alpha25(OH)(2)D(3)either with or
      without stimulation with TNFalpha or PMA. By contrast the increased production of
      MMP-9 and PGE(2)induced by PMA was significantly suppressed by concomitant
      treatment with 1alpha25(OH)(2)D(3). CONCLUSIONS: The demonstration of VDR
      expression by HAC in osteoarthritic cartilage was often associated with sites
      where MMP expression was prevalent, observations in contrast to their virtual
      absence in normal age-matched cartilage. Together with HAC in vitro studies, the
      data suggests that 1alpha25(OH)(2)D(3)contributes to the regulation of MMP and
      PGE(2)production by HAC in osteoarthritic cartilage.

PMID- 11467891
TI  - Evidence of chondrocyte repopulation in adult ovine articular cartilage following
      cryoinjury and long-term transplantation.
AB  - OBJECTIVE: To characterize the response of articular chondrocytes to a specific
      cryoinjury that leads to cluster formation following long-term transplantation.
      DESIGN: Osteochondral dowels from 20 adult sheep were cryopreserved to optimize
      the recovery of chondrocytes immediately after thawing. The dowels were
      transplanted as allografts and observed at 3 and 12 months. Chondrocyte
      distribution and viability was assessed using paravital dyes after
      transplantation. Chondrocyte phenotype was assessed by in situ hybridization and
      immunohistochemistry to detect type II collagen. An anticentrosome antibody was
      used to identify cells undergoing cell cycle progression towards mitosis.
      RESULTS: All cryopreserved grafts showed the presence of spheroidal clusters of
      chondrocytes 1 year after transplantation while the host cartilage adjacent to
      the graft appeared morphologically normal. The average size of the clusters
      increased from four cells at 3 months to 12 cells at 1 year. The chondrocytes in
      the clusters displayed newly formed type II collagen protein and mRNA. Some cells
      within clusters were observed with two centrosomes, indicative of cells
      progressing through the S phase of the cell cycle. CONCLUSION: Adult articular
      chondrocytes retain the ability to repopulate the matrix, an ability which is
      demonstrated with this specific cryoinjury. This may be an initial stage of
      cartilage regeneration.

PMID- 11467892
TI  - Validation of the Western Ontario and Mcmaster University osteoarthritis index in
      Asians with osteoarthritis in Singapore.
AB  - OBJECTIVE: To assess the reliability and validity of the Western Ontario and
      McMaster University Osteoarthritis Index (WOMAC) as an outcome measure in Asian
      patients with knee or hip osteoarthritis (OA) in Singapore. DESIGN: The WOMAC was
      administered twice 7 days apart to 66 consecutive English-speaking Chinese, Malay
      or Indian inpatients and outpatients with knee or hip OA seen at a tertiary
      referral centre through a structured interview, which also assessed demographic
      and other characteristics. Internal consistency was assessed using Cronbach's
      alpha, reliability using Spearman's correlations, intraclass correlations and
      repeatability coefficients, and relationships between WOMAC domains and known
      determinants of function using Spearman's correlations and the Mann-Whitney U
      test. RESULTS: The WOMAC showed good internal consistency (alpha=0.70 to 0.93)
      and good reliability, with intraclass correlations of 0.83 to 0.90 and mean test
      retest score differences of 0.02 to 0.13 points (possible range 4 points).
      Results of Likert scoring assessment supported the validity of the WOMAC when
      interpreted in the context of the close association between pain and physical
      function. Eight of nine a priori hypotheses relating WOMAC Pain and Physical
      Function scores to known determinants of function were present, supporting
      construct validity of this scale. CONCLUSION: The WOMAC is a valid and reliable
      outcome measure in Asian patients with OA in Singapore.

PMID- 11467893
TI  - Effect of load on articular cartilage matrix and the development of guinea-pig
      osteoarthritis.
AB  - OBJECTIVE: To study the biochemical changes in the early development of primary
      guinea-pig knee osteoarthritis (OA) and its dependence on load. METHODS: Load
      distribution was modified with below-knee amputation or femur valgus osteotomy in
      9-month-old guinea-pigs. Soft tissue sham operated animals served as controls.
      The composition of uncalcified and calcified articular cartilage at the medial
      and lateral tibial condyle was studied by analysing small and large proteoglycans
      (PG) by gel electrophoresis and sulfation pattern with high-performance liquid
      chromatography. Collagen concentration was also determined. RESULTS: The
      articular surfaces with a presumed higher load after surgery had a slight, but
      consistent, higher water content. Decreased load-on the ipsilateral medial
      condyle after femur osteotomy, and on the ipsilateral medial and lateral condyles
      following tibia amputation-was associated with an increased concentration of PGs,
      while this concentration decreased in condyles with increased load. Collagen
      concentration followed a similar pattern in the osteotomy group. In the amputated
      animals collagen concentration went down in all condyles, regardless of change of
      load. The aggregability and proportion of large and small PGs, the concentration
      of hyaluronan and the sulfation pattern of chondroitin sulfate was not affected
      by load. No consistent changes in PG, collagen or HA concentration, HA
      aggregability or sulfation pattern were seen in the calcified cartilage.
      CONCLUSIONS: Primary guinea-pig knee OA is a reproducible model similar to human
      OA. It develops slowly and biochemical changes seem to appear before the
      morphological lesions become evident. The biochemical events are affected by load
      redistribution and correlate closely to morphological changes. These changes
      eventually result in a cartilage devoid in aggrecan, as also has been
      demonstrated in advanced human OA. All of this makes primary guinea-pig OA a
      suitable model for studying early OA changes.

PMID- 11467894
TI  - Evaluation of chondrocyte cell-associated matrix metabolism by flow cytometry.
AB  - OBJECTIVE: To analyze human articular chondrocyte cell-associated matrix
      aggrecan, hyaluronan (HA) and type II collagen metabolism using flow cytometry,
      and to compare the results obtained for aggrecan with classic(35)Sulfate
      incorporation methods and an enzyme linked immunosorbent assay (ELISA). DESIGN:
      Human articular chondrocytes obtained from five donors were cultured in gelled
      agarose and tested for their response to different concentrations of interleukin
      1beta (IL-1beta). Synthesis and distribution of aggrecan in the cell-associated
      matrix (CAM), in the interterritorial matrix and in the nutrient medium of the
      chondrocytes in culture were analyzed using(35)Sulfate incorporation. The results
      were expressed as pg SO(4)incorporated in aggrecan per 1 x 10(6)cells/h. Flow
      cytometry with FITC-conjugated monoclonal antibodies against aggrecan and type II
      collagen, and with the biotinylated hyaluronic acid binding protein (b-HABP), was
      used to investigate the synthesis and accumulation of aggrecan, type II collagen
      and HA in the CAM of the cultured cells. The packing of these macromolecules in
      the CAM of the chondrocytes was assessed by measuring the mean fluorescence
      intensity (MFI) of the cell sample due to the binding of the specific monoclonal
      antibodies or b-HABP used. ELISA was used in parallel to quantify CAM aggrecans
      after these macromolecules were brought into solution with guanidinium chloride.
      Detection of aggrecan by flow cytometry was compared with(35)S-incorporation in
      chondrocytes from two subjects and with ELISA in a further two donors. RESULTS:
      IL-1beta suppressed aggrecan synthesis by chondrocytes in agarose. An IL-1beta
      dose-dependent suppression of(35)S-aggrecan in the CAM reflected the changes in
      the interterritorial matrix. IL-1beta-induced aggrecan breakdown was followed by
      a rise in(35)S-aggrecan metabolites in the incubation media of the cells in
      culture. Flow cytometry and ELISA confirmed this decreased accumulation of
      aggrecan in the CAM of the chondrocytes. The results obtained with flow cytometry
      were closely related to those obtained with ELISA.(35)S-incorporation, on the
      other hand, indirectly measures the glycosaminoglycan content of the aggrecan and
      does not necessarily reflect the absolute amount of aggrecan molecules.
      Therefore, the effects of IL-1beta on cell-associated aggrecan, where assessed
      with(35)S-incorporation, did not correlate with the results of the flow
      cytometric assays. Flow cytometry enabled the detection of an impaired synthesis
      and accumulation of HA and of type II collagen in the CAM of the cultured
      chondrocytes. IL-1beta-induced changes in CAM aggrecan and hyaluronan closely
      agreed. CONCLUSIONS: Flow cytometry offers an efficient tool to study the
      metabolism of the chondrocyte CAM. The MFI has been used as a parameter to
      quantify the ECM molecules in the CAM.

PMID- 11467895
TI  - High-resolution MRI detects cartilage swelling at the early stages of
      experimental osteoarthritis.
AB  - OBJECTIVE: The progressive early changes in cartilage and subchondral bone in an
      experimental model of osteoarthritis (OA) were investigated with high-resolution
      magnetic resonance imaging (MRI) and microradiography. METHODS: Partial medial
      meniscectomy was performed in the left knee of 16 rabbits. Four normal and four
      sham-operated additional rabbits were used as controls. Changes in cartilage and
      subchondral bone were sequentially assessed after surgery with MRI at 0, 2, 4, 6,
      8 and 10 weeks, subchondral bone variations quantified postoperatively on
      microradiographs of sagittal sections at 6 and 10 weeks and the macroscopic
      alterations graded according to the severity of joint changes. RESULTS: MRI
      demonstrated a progressive increase in the articular cartilage thickness in the
      weight-bearing area of the femur at weeks 4, 6 and 8 vs basal. Tibial cartilage
      thickness only showed a significant increment at week 6. No significant
      abnormalities were detected on X-rays in subchondral bone when compared to
      controls. Macroscopically, 4 weeks after the operation OA rabbits had only slight
      cartilage discoloration. Cartilage eburnation, pitting, superficial erosions and
      osteophytes were detected at week 6. These abnormalities were more evident at 8
      and 10 weeks after meniscectomy. CONCLUSION: The focal increase in cartilage
      thickness is one of the earliest measurable changes in OA and preceeds
      subchondral bone remodeling. The measurement of cartilage thickness variations
      with MRI can be used to follow the course of OA and to evaluate the potential
      beneficial effect of novel therapies.

PMID- 11467896
TI  - Magnetic resonance imaging of the knee in chronic knee pain. A 2-year follow-up.
AB  - OBJECTIVE: The aim of the study was to evaluate the change over time of cartilage
      defects, subchondral lesions and meniscal abnormalities of the knee using
      magnetic resonance (MR) imaging with a 2-year interval in patients with chronic
      knee pain. DESIGN: In the format of a prospective study of early osteoarthritis
      (OA), the signal knee (most painful at the inclusion in the study 1990) in 47
      individuals, 25 women and 22 men (aged 41-57 years, median 50), with chronic knee
      pain, with or without radiographically determined knee OA, were examined using MR
      imaging on a 1.0 T imager with a 2-year interval (median 25 months, range 21-30).
      Cartilage defects, subchondral lesions and meniscal abnormalities were recorded
      and compared in blind between the examinations. RESULTS: Five new cartilage
      defects and eight subchondral lesions appeared during the 2-year interval. Seven
      defects and seven subchondral lesions disappeared during the same time. Thirty
      two out of 93 cartilage defects (34%) and 19 out of 32 subchondral lesions (59%)
      displayed an increase or a decrease in size over time. A meniscal abnormality
      appeared in three locations, and disappeared in none. In 14 out of 54 locations
      (26%) with a meniscal abnormality an increase or a decrease of the abnormality
      was recorded over time and no abnormality decreased. CONCLUSIONS: After the 2
      years of observation it was possible to register, using MR imaging, the
      appearance, increase, decrease and disappearance of cartilage defects,
      subchondral lesions and meniscal abnormalities in middle-aged people with chronic
      knee pain. This has to be considered in studies of the natural course of knee OA
      as well as in studies of the intraarticular effect of pharmacological treatment
      aiming at cartilage repair or protection.

PMID- 11467897
TI  - The effect of dynamic mechanical compression on nitric oxide production in the
      meniscus.
AB  - OBJECTIVE: The menisci play an important role in the biomechanics of the knee,
      and loss of meniscal function has been associated with progressive degenerative
      changes of the joint in rheumatoid arthritis as well as in osteoarthritis.
      However, little is known about the underlying mechanisms that link meniscal
      injury or degeneration to arthritis. Meniscal fibrochondrocytes respond to
      environmental mediators such as growth factors and cytokines, but the influence
      of mechanical stress on their metabolic activity is not well understood. Nitric
      oxide (NO) is believed to play a role in mechanical signal transduction, and
      there is also significant evidence of its role in cartilage and meniscus
      degeneration. The goal of this study was to determine if meniscal
      fibrochondrocytes respond to mechanical stress by increasing NO production in
      vitro. DESIGN: Explants of lateral and medial porcine menisci were dynamically
      compressed in a precisely controlled manner, and NO production, nitric oxide
      synthase antigen expression and cell viability were measured. The relative
      responses of the meniscal surface and deep layers to dynamic compression were
      also investigated separately. RESULTS: Meniscal NO production was significantly
      (P< 0.01) increased by dynamic compression in both the medial and lateral
      menisci. Dynamically compressed menisci contained inducible nitric oxide synthase
      antigen, while uncompressed menisci did not. Significant (P< 0.05) zonal
      differences were observed in basal and compression-induced NO production.
      DISCUSSION: Our findings provide direct evidence that dynamic mechanical stress
      influences the biological activity of meniscal cells. These results suggest that
      NO production in vivo may be in part regulated by mechanical stress acting upon
      the menisci. Since NO affects matrix metabolism in various intraarticular
      tissues, alterations in the distribution and magnitude of stress in the menisci
      may have important metabolic as well as biomechanical consequences on joint
      physiology and function.

PMID- 11467898
TI  - Structure modification in knee osteoarthritis: methodology and outcome
      parameters.
AB  - Managing osteoarthritis (OA) with structure-modifying agents (SMAs) is an
      important emerging topic receiving increased attention from both lay individuals
      and health care professionals as a promising alternative in the management of OA.
      OBJECTIVE: To review the methodology and outcome parameters purported to be used
      in the assessment of the structure-modifying potential of various interventions.
      DESIGN: A Medline search was performed to select the relevant published articles.
      This review does not go into detail about various aspects of the design and
      conduct of structure-modifying studies; however, a vast number of relevant
      references are provided and may be accessed by interested readers. RESULTS:
      Enhancing the feasibility of SMAs trials aimed at documenting efficacy can be
      accomplished by carefully selecting: (1) the outcome parameters, (2) the imaging
      methodology, and (3) the patient population. Most of the relevant issues that
      need to be considered by investigators before embarking on a study of this nature
      have been addressed in this article. CONCLUSION: Most of the evidence to date
      focuses on the superiority of the radiographic-based techniques in measuring
      joint space narrowing among a homogeneous population of OA patients. More
      research is warranted before other techniques such as ultrasound, chondroscopy,
      and magnetic resonance imaging, can be proven to be reliable.

PMID- 11467899
TI  - How severe must repetitive loading be to kill chondrocytes in articular
      cartilage?
AB  - OBJECTIVE: Little is known about the effects of severe repetitive loading on
      articular cartilage chondrocytes, even though epidemiological studies associate
      this type of loading with osteoarthritis. We hypothesize that repetitive loading
      can kill cartilage chondrocytes in a dose-related manner. DESIGN: Large cartilage
      on-bone specimens were cut from the patella groove of bovine knees obtained
      directly from a slaughterhouse. Cartilage was loaded using a flat impermeable
      indenter in such a manner that the loaded region was supported naturally by
      surrounding cartilage and subchondral bone. Specimens received 3600 cycles of
      compressive loading at 1 Hz, with the peak load lying in the range 1-70% of the
      force required to damage cartilage in a single loading cycle (35 MPa). Cell
      viability was assessed in thick sections of loaded and control cartilage using a
      paravital staining method: fluorescein diacetate stained live cells green, and
      propidium iodide stained dead cells red. The assay was validated on cartilage
      which had been subjected to repeated freeze-thaw cycles to kill the chondrocytes.
      RESULTS: Paravital staining revealed 100% cell death after one freeze-thaw cycle
      at -196 degrees C and three cycles at -20 degrees C. Baseline chondrocyte
      viability was 80% in unloaded cartilage, and viability decreased when applied
      compressive loading exceeded 6 MPa. Above this threshold, cell viability was
      inversely proportional to applied stress. When gross damage to the cartilage
      surface first became evident, above 14 MPa, 40% of cells remained viable. Load
      induced chondrocyte death was greatest in the surface zone, and extended beyond
      the loaded area. Electron micrographs indicated that some cells were dying by
      apoptosis. CONCLUSIONS: Some chondrocytes are much more vulnerable to repetitive
      mechanical loading than others, suggesting that vigorous activity may lead to
      cell death in articular cartilage.

PMID- 11467900
TI  - Functional MRI of the human amygdala?
AB  - In view of an increasing number of publications that deal with functional mapping
      of the human amygdala using blood oxygenation-level-dependent (BOLD) magnetic
      resonance imaging, we reevaluated the underlying image quality of T2*-weighted
      echoplanar imaging (EPI) and fast low angle shot (FLASH) sequences at 2.0-T with
      regard to susceptibility-induced signal losses and geometric distortions. Apart
      from the timing of the gradient echoes, the degree of susceptibility influences
      is controlled by the image voxel size. Whereas published amygdala studies report
      voxel sizes ranging from 22 to 125 microl, the present results suggest that
      reliable imaging of the amygdala with BOLD sensitivity requires voxel sizes of 4
      to 8 microl or less. Preferentially, acquisitions should be performed with a
      coronal section orientation. Although high-resolution BOLD MRI is at the expense
      of temporal resolution and volume coverage, it seems to provide the only solution
      to this physical problem.

PMID- 11467901
TI  - The functional anatomy of inhibition processes investigated with the Hayling
      task.
AB  - The cortical areas involved in inhibition processes were examined with positron
      emission tomography (PET). The tasks administered to subjects were an adaptation
      of the Hayling test. In the first condition (response initiation), subjects had
      to complete sentences with a word clearly suggested by the context, whereas in
      the second condition (response inhibition), subjects had to produce a word that
      made no sense in the context of the sentence. Results indicated that the response
      initiation processes were associated to increases of activity in the left
      inferior frontal gyrus (BA 45/47), whereas response inhibition processes led to
      increases in a network of left prefrontal areas, including the middle (BA 9 and
      BA 10) and inferior (BA 45) frontal areas.

PMID- 11467902
TI  - Evidence for premotor cortex activity during dynamic visuospatial imagery from
      single-trial functional magnetic resonance imaging and event-related slow
      cortical potentials.
AB  - A strong correspondence has been repeatedly observed between actually performed
      and mentally imagined object rotation. This suggests an overlap in the brain
      regions involved in these processes. Functional neuroimaging studies have
      consistently revealed parietal and occipital cortex activity during dynamic
      visuospatial imagery. However, results concerning the involvement of higher-order
      cortical motor areas have been less consistent. We investigated if and when
      premotor structures are active during processing of a three-dimensional cube
      comparison task that requires dynamic visuospatial imagery. In order to achieve a
      good temporal and spatial resolution, single-trial functional magnetic resonance
      imaging (fMRI) and scalp-recorded event-related slow cortical potentials (SCPs)
      were recorded from the same subjects in two separate measurement sessions. In
      order to reduce inter-subject variability in brain activity due to individual
      differences, only male subjects (n = 13) with high task-specific ability were
      investigated. Functional MRI revealed consistent bilateral activity in the
      occipital (Brodmann area BA18/19) and parietal cortex (BA7), in lateral and
      medial premotor areas (BA6), the dorsolateral prefrontal cortex (BA9), and the
      anterior insular cortex. The time-course of SCPs indicated that task-related
      activity in these areas commenced approximately 550-650 ms after stimulus
      presentation and persisted until task completion. These results provide strong
      and consistent evidence that the human premotor cortex is involved in dynamic
      visuospatial imagery.

PMID- 11467903
TI  - Quantifying head motion associated with motor tasks used in fMRI.
AB  - In functional magnetic resonance imaging (fMRI) studies, long experiment times
      and small intensity changes associated with brain activation frequently lead to
      image artifacts due to head motion. Methods to minimize and correct for head
      motion by restraint, fast imaging, and retrospective image registration are
      typically combined but do not completely solve the problem, particularly for
      specific patient populations. As an initial step toward optimizing future designs
      of head restraints and improving motion correction techniques, the head motion
      characteristics of groups of stroke subjects, age-matched controls, and young
      adults were investigated with the aid of an MR simulator and a highly accurate
      position tracking system. Position measurements were recorded during motor tasks
      involving either the hand or the foot. Head motion was strongly dependent on the
      subject group and less upon the task conditions based on ANOVA calculations (P <
      0.05). The stroke subjects exhibited approximately twice the head motion compared
      to that of age-matched controls, and the latter's head motion was about twice
      that of young adults. Moreover, the range of head motion in stroke subjects over
      all tasks was approximately 2 +/- 1 mm, with the motion occurring predominantly
      as translation in the superior-inferior direction and pitch rotation (nodding).
      These results lead to several recommendations on the design of fMRI motor
      experiments and suggest that improved motion correction strategies are required
      to examine such patient populations comprehensively.

PMID- 11467904
TI  - In vivo mapping of gray matter loss with voxel-based morphometry in mild
      Alzheimer's disease.
AB  - Up till now, the study of regional gray matter atrophy in Alzheimer's disease
      (AD) has been assessed with regions of interest, but this method is time
      consuming, observer dependent, and poorly reproducible (especially in terms of
      cortical regions boundaries) and in addition is not suited to provide a
      comprehensive assessment of the brain. In this study, we have mapped gray matter
      density by means of voxel-based morphometry on T1-weighted MRI volume sets in 19
      patients with mild AD and 16 healthy subjects of similar age and gender ratio and
      report highly significant clusters of gray matter loss with almost symmetrical
      distribution, affecting mainly and in decreasing order of significance the medial
      temporal structures, the posterior cingulate gyrus and adjacent precuneus, and
      the temporoparietal association and perisylvian neocortex, with only little
      atrophy in the frontal lobe. The findings are discussed in light of previous
      studies of gray matter atrophy in AD based either on postmortem or neuroimaging
      data and in relation to PET studies of resting glucose consumption. The
      limitations of the method are also discussed in some detail, especially with
      respect to the segmentation and spatial normalization procedures as they apply to
      pathological brains. Some potential applications of voxel-based morphometry in
      the study of AD are also mentioned.

PMID- 11467905
TI  - A parametric fMRI study of overt and covert shifts of visuospatial attention.
AB  - It has recently been demonstrated that a cortical network of visuospatial and
      oculomotor control areas is active for covert shifts of spatial attention (shifts
      of attention without eye movements) as well as for overt shifts of spatial
      attention (shifts of attention with saccadic eye movements). Studies examining
      activity in this visuospatial network during attentional shifts at a single rate
      have given conflicting reports about how the activity differs for overt and
      covert shifts. To better understand how the network subserves attentional shifts,
      we performed a parametric study in which subjects made either overt attentional
      shifts or covert attentional shifts at three different rates (0.2, 1.0, and 2.0
      Hz). At every shift rate, both overt and covert shifts of visuospatial attention
      induced activations in the precentral sulcus, intraparietal sulcus, and lateral
      occipital cortex that were of greater amplitude for overt than during covert
      shifting. As the rate of attentional shifts increased, responses in the
      visuospatial network increased in both overt and covert conditions but this
      parametric increase was greater during overt shifts. These results confirm that
      overt and covert attentional shifts are subserved by the same network of areas.
      Overt shifts of attention elicit more neural activity than do covert shifts,
      reflecting additional activity associated with saccade execution. An additional
      finding concerns the anatomical organization of the visuospatial network. Two
      distinct activation foci were observed within the precentral sulcus for both
      overt and covert attentional shifts, corresponding to specific anatomical
      landmarks. We therefore reappraise the correspondence of these two precentral
      areas with the frontal eye fields.

PMID- 11467906
TI  - Ethanol modulates cortical activity: direct evidence with combined TMS and EEG.
AB  - The motor cortex of 10 healthy subjects was stimulated by transcranial magnetic
      stimulation (TMS) before and after ethanol challenge (0.8 g/kg resulting in blood
      concentration of 0.77 +/- 0.14 ml/liter). The electrical brain activity resulting
      from the brief electromagnetic pulse was recorded with high-resolution
      electroencephalography (EEG) and located using inversion algorithms. Focal
      magnetic pulses to the left motor cortex were delivered with a figure-of-eight
      coil at the random interstimulus interval of 1.5-2.5 s. The stimulation intensity
      was adjusted to the motor threshold of abductor digiti minimi. Two conditions
      before and after ethanol ingestion (30 min) were applied: (1) real TMS, with the
      coil pressed against the scalp; and (2) control condition, with the coil
      separated from the scalp by a 2-cm-thick piece of plastic. A separate EMG control
      recording of one subject during TMS was made with two bipolar platinum needle
      electrodes inserted to the left temporal muscle. In each condition, 120 pulses
      were delivered. The EEG was recorded from 60 scalp electrodes. A peak in the EEG
      signals was observed at 43 ms after the TMS pulse in the real-TMS condition but
      not in the control condition or in the control scalp EMG. Potential maps before
      and after ethanol ingestion were significantly different from each other (P =
      0.01), but no differences were found in the control condition. Ethanol changed
      the TMS-evoked potentials over right frontal and left parietal areas, the
      underlying effect appearing to be largest in the right prefrontal area. Our
      findings suggest that ethanol may have changed the functional connectivity
      between prefrontal and motor cortices. This new noninvasive method provides
      direct evidence about the modulation of cortical connectivity after ethanol
      challenge.

PMID- 11467907
TI  - An efficient algorithm for topologically correct segmentation of the cortical
      sheet in anatomical mr volumes.
AB  - Polygon-mesh representations of the cortices of individual subjects are of
      anatomical interest, aid visualization of functional imaging data and provide
      important constraints for their statistical analysis. Due to noise and partial
      volume sampling, however, conventional segmentation methods rarely yield a voxel
      object whose outer boundary represents the folded cortical sheet without
      topological errors. These errors, called handles, have particularly deleterious
      effects when the polygon mesh constructed from the segmented voxel representation
      is inflated or flattened. So far handles had to be removed by cumbersome manual
      editing, or the computationally more expensive method of reconstruction by
      morphing had to be used, incorporating the a priori constraint of simple topology
      into the polygon-mesh model. Here we describe a linear time complexity algorithm
      that automatically detects and removes handles in presegmentations of the cortex
      obtained by conventional methods. The algorithm's modifications reflect the true
      structure of the cortical sheet. The core component of our method is a region
      growing process that starts deep inside the object, is prioritized by the
      distance-to-surface of the voxels considered for inclusion and is selftouching
      sensitive, i.e., voxels whose inclusion would add a handle are never included.
      The result is a binary voxel object identical to the initial object except for
      "cuts" located in the thinnest part of each handle. By applying the same method
      to the inverse object, an alternative set of solutions is determined, correcting
      the errors by addition instead of deletion of voxels. For each handle separately,
      the solution more consistent with the intensities of the original anatomical MR
      scan is chosen. The accuracy of the resulting polygon-mesh reconstructions has
      been validated by visual inspection, by quantitative comparison to an expert's
      manual corrections, and by crossvalidation between reconstructions from different
      scans of the same subject's cortex.

PMID- 11467908
TI  - On multivariate spectral analysis of fMRI time series.
AB  - Most of functional magnetic resonance imaging (fMRI) time series analysis is
      based on single voxel data evaluation using parametric statistical tests. The
      result of such an analysis is a statistical parametric map. Voxels with a high
      significance value in the parametric test are interpreted as activation regions
      stimulated by the experimental task. However, for the investigation of functional
      connectivities it would be interesting to get some detailed information about the
      temporal dynamics of the blood oxygen level-dependent (BOLD) signal. For
      investigating that behavior, a method for fMRI data analysis has been developed
      that is based on Wiener theory of spectral analysis for multivariate time series.
      Spectral parameters such as coherence measure and phase lead can be estimated.
      The resulting maps give detailed information on brain regions that belong to a
      network structure and also show the temporal behavior of the BOLD response
      function. This paper describes the method and presents a visual fMRI experiment
      as an example to demonstrate the results.

PMID- 11467909
TI  - Functional MRI in patients with band heterotopia.
AB  - Functional activation associated with a motor task (fist movements) was studied
      in three patients with band heterotopias by fMRI. In two patients, additional
      visual fMRI studies were performed using a flickering checkerboard stimulus. In
      all patients activation of the outer cortex and of the inner neuronal band could
      be found during performance of the motor task. Visual stimulation elicited a
      normal activation pattern without activation of the ectopic neuronal layer in one
      patient; in another patient activation extended toward the ventricular wall,
      i.e., along the route of embryonic neuronal migration. The potential
      participation of ectopic neuronal tissue in physiologic cerebral functions is of
      clinical impact in patients with neuronal heterotopias suffering from medically
      intractable seizures prior to epilepsy surgery.

PMID- 11467910
TI  - In vivo assessment of human visual system connectivity with transcranial
      electrical stimulation during functional magnetic resonance imaging.
AB  - Functional magnetic resonance imaging (fMRI) was used to investigate local and
      distant cerebral activation induced by transcranial electrical stimulation in
      order to noninvasively map functional connectivity in the human visual system.
      Stimulation with lateromedially directed currents and the anode 4.5 cm dorsally
      to the inion over the right visual cortex induced phosphenes extending into the
      contralateral lower quadrant of the visual field. fMRI showed a focal hemodynamic
      response underneath the anode in extrastriate cortex and distant coactivation in
      subcortical (lateral geniculate nucleus), cortical visual (striate and
      extrastriate), and visuomotor areas (frontal and supplementary eye fields). This
      pattern of activation resembles a network of presumably interconnected visual and
      visuomotor areas. Analysis of activation sites supplies new information about
      cerebral correlates of phosphenes and shows that the cortical region underneath
      the cranial stimulation site is not necessarily the origin of behavioral and/or
      perceptual effects of transcranial stimulation. We conclude that combining
      transcranial electrical stimulation of neural tissue with simultaneous fMRI
      offers the possibility to study noninvasively cerebral connectivity in the human
      brain.

PMID- 11467911
TI  - Auditory sensory memory and the cholinergic system: implications for Alzheimer's
      disease.
AB  - Auditory sensory memory represents one of the simplest types of short-term memory
      that can be studied electrophysiologically with mismatch negativity (MMN); a
      specific auditory event-related potential indexing automatic comparison of
      incoming stimuli to an existing memory trace. Previous results suggest that
      auditory sensory memory deteriorates in aging and especially in Alzheimer's
      disease (AD). It has remained unsettled, however, whether MMN is regulated by the
      cholinergic system, which is deteriorated in AD contributing to cognitive
      impairments. We recorded cortical auditory responses with a magnetometer from 13
      healthy subjects after intravenous injection of scopolamine, centrally acting
      cholinergic antagonist, or glycopyrrolate, a drug with a peripheral
      anticholinergic properties without penetrating the blood-brain barrier, using a
      double-blind protocol. Scopolamine reduced MMNm amplitude in response to
      frequency, but not duration, change, increased P50m amplitude, and delayed N100m
      latency. These findings suggest that the cholinergic system regulates the
      frequency-specific comparison of incoming stimuli to existing memory trace and
      modulates the preattentive processing related to stimulus detection. Further,
      neural mechanisms responsible for cortical frequency- and duration-specific
      discrimination appear to have different sensitivities to cholinergic modulation.
      Auditory evoked potentials might be suitable to monitor cholinergic activity in
      AD.

PMID- 11467912
TI  - Topographic time-frequency decomposition of the EEG.
AB  - Frequency-transformed EEG resting data has been widely used to describe normal
      and abnormal brain functional states as function of the spectral power in
      different frequency bands. This has yielded a series of clinically relevant
      findings. However, by transforming the EEG into the frequency domain, the
      initially excellent time resolution of time-domain EEG is lost. The topographic
      time-frequency decomposition is a novel computerized EEG analysis method that
      combines previously available techniques from time-domain spatial EEG analysis
      and time-frequency decomposition of single-channel time series. It yields a new,
      physiologically and statistically plausible topographic time-frequency
      representation of human multichannel EEG. The original EEG is accounted by the
      coefficients of a large set of user defined EEG like time-series, which are
      optimized for maximal spatial smoothness and minimal norm. These coefficients are
      then reduced to a small number of model scalp field configurations, which vary in
      intensity as a function of time and frequency. The result is thus a small number
      of EEG field configurations, each with a corresponding time-frequency (Wigner)
      plot. The method has several advantages: It does not assume that the data is
      composed of orthogonal elements, it does not assume stationarity, it produces
      topographical maps and it allows to include user-defined, specific EEG elements,
      such as spike and wave patterns. After a formal introduction of the method,
      several examples are given, which include artificial data and multichannel EEG
      during different physiological and pathological conditions.

PMID- 11467913
TI  - Timing and localization of movement-related spectral changes in the human peri
      Rolandic cortex: intracranial recordings.
AB  - Event-related spectral power (ERSP) was measured from intracranial EEG and used
      to characterize the time-course and localization of the Rolandic mu rhythms in 12
      patients during the delayed recognition of words or faces (DR) and the
      discrimination of simple lateralized visual targets (LVD). On each trial, the
      subject decided whether to make manual response (Go) or not (NoGo). ERSP
      increased on both Go and NoGo trials in peri-Rolandic regions of all subjects
      with a peak latency of approximately 330-ms poststimulus and duration of 260 ms
      during the DR task. The peak of this ERSP increase preceded movement by
      approximately 300 ms. All subjects produced a subsequent movement specific ERSP
      decrease of peri-Rolandic mu rhythms (starting approximately 90 ms before the
      average reaction time) with an peak latency of approximately 800 ms and duration
      of approximately 520 ms. The LVD task produced bilateral movement-selective
      readiness potentials and reproduced the movement-specific late ERSP decreases
      seen in the DR task (strongest from 7-24 Hz). Furthermore, the LVD task
      demonstrated that the late movement-related ERSP decrease is larger for the
      contralateral hand. However, the LVD task did not consistently reproduce the
      early ERSP increase seen in the DR task. Movement-related ERSP decreases were
      widespread, occurring in pre- and post-Rolandic as well as primary-motor,
      supplemental motor, and cingulate cortical regions. Other cortical areas
      including frontal, temporal, and occipital regions did not show movement-related
      ERSP changes. Peri-Rolandic ERSP decreases in mu rhythms correlate with the
      generation of a motor command. The early increases in mu may reflect a transient
      state of motor inhibition just prior to motor execution.

PMID- 11467914
TI  - Nonadditive two-way ANOVA for event-related fMRI data analysis.
AB  - A significant recent development in functional magnetic resonance imaging (fMRI)
      is the introduction of event-related fMRI, also known as time-resolved fMRI.
      Because the exact shape of the MR response in an event-related fMRI experiment is
      often not known, traditional methods developed for block design experiments, such
      as t test and correlation analysis, are not well-suited for extracting activated
      pixels from the event-related data. In this work, a statistical technique based
      on nonadditive two-way analysis of variance is developed for use in event-related
      studies. Theoretical and experimental work were carried out for establishing a
      statistical threshold to determine pixel activation. Experimental studies were
      performed to demonstrate the utility of this approach.

PMID- 11467915
TI  - Interdependence of nonoverlapping cortical systems in dual cognitive tasks.
AB  - One of the classic questions about human thinking concerns the limited ability to
      perform two cognitive tasks concurrently, such as a novice driver's difficulty in
      simultaneously driving and conversing. Limitations on the concurrent performance
      of two unrelated tasks challenge the tacitly assumed independence of two brain
      systems that seemingly have little overlap. The current study used fMRI
      (functional magnetic resonance imaging) to measure cortical activation during the
      concurrent performance of two high-level cognitive tasks that involve different
      sensory modalities and activate largely nonoverlapping areas of sensory and
      association cortex. One task was auditory sentence comprehension, and the other
      was the mental rotation of visually depicted 3-D objects. If the neural systems
      underlying the two tasks functioned independently, then in the dual task the
      brain activation in the main areas supporting the cognitive processing should be
      approximately the conjunction of the activation for each of the two tasks
      performed alone. We found instead that in the dual task, the activation in
      association areas (primarily temporal and parietal areas of cortex) was
      substantially less than the sum of the activation when the two tasks were
      performed alone, suggesting some mutual constraint among association areas. A
      similar result was obtained for sensory areas as well.

PMID- 11467916
TI  - Detection of audio-visual integration sites in humans by application of
      electrophysiological criteria to the BOLD effect.
AB  - Electrophysiological studies in nonhuman primates and other mammals have shown
      that sensory cues from different modalities that appear at the same time and in
      the same location can increase the firing rate of multisensory cells in the
      superior colliculus to a level exceeding that predicted by summing the responses
      to the unimodal inputs. In contrast, spatially disparate multisensory cues can
      induce a profound response depression. We have previously demonstrated using
      functional magnetic resonance imaging (fMRI) that similar indices of crossmodal
      facilitation and inhibition are detectable in human cortex when subjects listen
      to speech while viewing visually congruent and incongruent lip and mouth
      movements. Here, we have used fMRI to investigate whether similar BOLD signal
      changes are observable during the crossmodal integration of nonspeech auditory
      and visual stimuli, matched or mismatched solely on the basis of their temporal
      synchrony, and if so, whether these crossmodal effects occur in similar brain
      areas as those identified during the integration of audio-visual speech. Subjects
      were exposed to synchronous and asynchronous auditory (white noise bursts) and
      visual (B/W alternating checkerboard) stimuli and to each modality in isolation.
      Synchronous and asynchronous bimodal inputs produced superadditive BOLD response
      enhancement and response depression across a large network of polysensory areas.
      The most highly significant of these crossmodal gains and decrements were
      observed in the superior colliculi. Other regions exhibiting these crossmodal
      interactions included cortex within the superior temporal sulcus, intraparietal
      sulcus, insula, and several foci in the frontal lobe, including within the
      superior and ventromedial frontal gyri. These data demonstrate the efficacy of
      using an analytic approach informed by electrophysiology to identify multisensory
      integration sites in humans and suggest that the particular network of brain
      areas implicated in these crossmodal integrative processes are dependent on the
      nature of the correspondence between the different sensory inputs (e.g. space,
      time, and/or form).

PMID- 11467917
TI  - A temporoparietal and prefrontal network for retrieving the spatial context of
      lifelike events.
AB  - Virtual reality (VR) and event-related functional magnetic resonance imaging were
      used to study memory for the spatial context of controlled but lifelike events.
      Subjects received a set of objects from two different people in two different
      places within a VR environment. Memory for the objects, and for where and from
      whom they were received was tested by putting the subject back into a place in
      the company of a person and giving a paired forced choice of objects. In four
      conditions objects had to be chosen according to different criteria: which was
      received in that place, which was received from that person, which object was
      recognized, and which object was widest. Event-related functional magnetic
      resonance imaging was performed during testing to identify areas involved in
      retrieval of the spatial context of an event. A network of areas was identified
      consisting of a temporoparietal pathway running between the precuneus and
      parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left
      hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and
      anterior prefrontal cortices, and the anterior cingulate. Of these areas the
      parahippocampal, right posterior parietal, and posteriodorsal medial parietal
      areas were specifically involved in retrieval of spatial context compared to
      retrieval of nonspatial context. The posterior activations are consistent with a
      model of long-term storage of allocentric representations in medial temporal
      regions with translation to body-centered and head-centered representations
      computed in right posterior parietal cortex and buffered in the temporoparietal
      pathway so as to provide an imageable representation in the precuneus. Prefrontal
      activations are consistent with strategic retrieval processes, including those
      required to overcome the interference between the highly similar events.

PMID- 11467918
TI  - Mental imagery of high- and low-resolution gratings activates area 17.
AB  - Some, but not all, previous neuroimaging studies of visual mental imagery have
      found that Area 17 (primary visual cortex) is activated when people visualize
      objects. The present study was designed to test the hypothesis that the necessary
      degree of resolution of the mental image is a determining factor in whether Area
      17 is activated during imagery. Eight male subjects visualized and compared sets
      of stripes that required high or low resolution to resolve, while their brains
      were scanned using 15O(CO2) positron emission tomography (PET). When imagery in
      general (visualization of high- and low-resolution gratings stimuli combined) was
      compared to an auditory baseline condition where subjects did not visualize, Area
      17 was activated. However, region of interest (ROI) and statistical parametric
      mapping (SPM) analyses revealed no difference between imagery conditions using
      high- and low-resolution stimuli. These results indicate that the resolution of
      the stimuli alone does not necessarily determine whether Area 17 will be
      activated during visual mental imagery.

PMID- 11467919
TI  - Explicit and incidental facial expression processing: an fMRI study.
AB  - Considerable evidence indicates that processing facial expression involves both
      subcortical (amygdala and basal ganglia) and cortical (occipito-temporal,
      orbitofrontal, and prefrontal cortex) structures. However, the specificity of
      these regions for single types of emotions and for the cognitive demands of
      expression processing, is still unclear. This functional magnetic resonance
      imaging (fMRI) study investigated the neural correlates of incidental and
      explicit processing of the emotional content of faces expressing either disgust
      or happiness. Subjects were examined while they were viewing neutral, disgusted,
      or happy faces. The incidental task required subjects to decide about face
      gender, the explicit task to decide about face expression. In the control task
      subjects were requested to detect a white square in a greyscale mosaic stimulus.
      Results showed that the left inferior frontal cortex and the bilateral occipito
      temporal junction responded equally to all face conditions. Several cortical and
      subcortical regions were modulated by task type, and by facial expression. Right
      neostriatum and left amygdala were activated when subjects made explicit
      judgements of disgust, bilateral orbitofrontal cortex when they made judgement of
      happiness, and right frontal and insular cortex when they made judgements about
      any emotion.

PMID- 11467920
TI  - Interhemispheric differences of sensory hand areas after monohemispheric stroke:
      MEG/MRI integrative study.
AB  - Seventeen clinically stabilized monohemispheric stroke patients were studied in
      order to investigate the chronic topographical modifications induced on primary
      sensory cortical hand areas by a monohemispheric stroke within the middle
      cerebral artery territory. Magnetoencephalographic (MEG) localization of the
      cortical areas activated following electrical separate stimulation of the median
      nerve, thumb, and little fingers was integrated with magnetic resonance imaging.
      Spatial localization of Equivalent Current Dipoles (ECDs) of the short-latency
      cortical responses generated in primary sensory cortices, "hand area" (distance
      between 1st and 5th digits ECDs), interhemispheric differences of such
      parameters, as well as of somatosensory-evoked fields waveshapes were
      investigated and compared with a control population. Lesions involving the
      cortico-subcortical areas receiving sensory input from the hand induced excessive
      asymmetry of MEG spatial parameters and response morphology between the
      unaffected (UH) and the affected hemisphere (AH). "Hand area" was significantly
      larger on AH in 20% of cases after a subcortical, and in 13% after a cortical,
      lesion. Responses from AH were excessively delayed in 20% ECDs. Interhemispheric
      ECDs strength differences were larger than normal in 25% of cases after both
      types of lesions; the strength in the AH being enlarged after all cortical, and
      only 24% of subcortical strokes. In a significant percentage of monohemispheric
      strokes, excessive interhemispheric differences were found between AH and UH,
      suggesting that brain areas outside the normal boundaries and usually not reached
      by a dense sensory input from the opposite hand and fingers may act as
      somatosensory "hand" centers. Correlation analysis between clinical outcome and
      cortical reorganization in the AH suggests that this mechanism is linked with
      hand sensorimotor recovery.

PMID- 11467921
TI  - Spatial normalization of brain images with focal lesions using cost function
      masking.
AB  - In studies of patients with focal brain lesions, it is often useful to coregister
      an image of the patient's brain to that of another subject or a standard
      template. We refer to this process as spatial normalization. Spatial
      normalization can improve the presentation and analysis of lesion location in
      neuropsychological studies; it can also allow other data, for example from
      functional imaging, to be compared to data from other patients or normal
      controls. In functional imaging, the standard procedure for spatial normalization
      is to use an automated algorithm, which minimizes a measure of difference between
      image and template, based on image intensity values. These algorithms usually
      optimize both linear (translations, rotations, zooms, and shears) and nonlinear
      transforms. In the presence of a focal lesion, automated algorithms attempt to
      reduce image mismatch between template and image at the site of the lesion. This
      can lead to significant inappropriate image distortion, especially when nonlinear
      transforms are used. One solution is to use cost-function masking-masking the
      areas used in the calculation of image difference-to exclude the area of the
      lesion, so that the lesion does not bias the transformations. We introduce and
      evaluate this technique using normalizations of a selection of brains with focal
      lesions and normal brains with simulated lesions. Our results suggest that cost
      function masking is superior to the standard approach to this problem, which is
      affine-only normalization; we propose that cost-function masking should be used
      routinely for normalizations of brains with focal lesions.

PMID- 11467922
TI  - In vivo short echo time 1H-magnetic resonance spectroscopic imaging (MRSI) of the
      temporal lobes.
AB  - Two different methodologies for obtaining PRESS-localized magnetic resonance
      spectroscopic imaging (MRSI) data from the mesial and lateral temporal lobes were
      investigated. The study used short echo times (30 ms) and long repetition times
      (3000 ms) to minimize relaxation effects. Inhomogeneity and spectral distortions
      from the proximity of the temporal bones precluded the attainment of consistently
      good-quality data from both temporal lobes at once. Even when the right and left
      temporal lobes were studied separately, distortions often disturbed spectra from
      the anterior lateral temporal lobe. Quantitative analysis using LCModel was
      therefore performed only on the posterior lateral temporal lobe, and the
      posterior, middle, and anterior mesial temporal lobe. No significant left-right
      differences in metabolite content were found in a series of 10 controls.
      Significantly higher concentrations of myoinositol and choline were found in the
      anterior mesial temporal lobe, even when grey matter content was included as a
      covariate. The concentration of N-acetyl aspartate plus N-acetyl aspartyl
      glutamate (NAc) was not found to vary significantly along the length of the
      hippocampus. The previously observed lower anterior ratios of NAA to creatine
      plus choline (NAA/(Cr + Cho) may instead have been due to higher anterior
      choline. Large differences in metabolite concentrations were seen between
      posterior lateral temporal lobe (predominantly subcortical white matter) and the
      posterior mesial temporal lobe, most notably lower creatine, glutamate/glutamine,
      and myo-inositol, and higher NAA/(Cr + Cho) in the lateral than mesial temporal
      lobe. This pattern was similar to that previously seen for grey/white matter
      differences in the frontal, parietal and occipital regions.

PMID- 11467923
TI  - Language switching and language representation in Spanish-English bilinguals: an
      fMRI study.
AB  - The current experiment was designed to investigate the nature of cognitive
      control in within- and between-language switching in bilingual participants. To
      examine the neural substrate of language switching we used functional magnetic
      resonance imaging (fMRI) as subjects named pictures in one language only or
      switched between languages. Participants were also asked to name (only in
      English) a separate set of pictures as either the actions or the objects depicted
      or to switch between these two types of responses on each subsequent picture.
      Picture naming compared to rest revealed activation in the dorsolateral
      prefrontal cortex, which extended down into Broca's area in the left hemisphere.
      There were no differences in the activation pattern for each language. English
      and Spanish both activated overlapping areas of the brain. Similarly, there was
      no difference in activation for naming actions or objects in English. However,
      there was increased intensity of activation in the dorsolateral prefrontal cortex
      for switching between languages relative to no-switching, an effect which was not
      observed for naming of actions or objects in English. We suggest that the
      dorsolateral prefrontal cortex serves to attenuate interference that results from
      having to actively enhance and suppress two languages in alternation. These
      results are consistent with the view that switching between languages involves
      increased general executive processing. Finally, our results are consistent with
      the view that different languages are represented in overlapping areas of the
      brain in early bilinguals.

PMID- 11467924
TI  - Reactivation of motor brain areas during explicit memory for actions.
AB  - Recent functional brain imaging studies have shown that sensory-specific brain
      regions that are activated during perception/encoding of sensory-specific
      information are reactivated during memory retrieval of the same information. Here
      we used PET to examine whether verbal retrieval of action phrases is associated
      with reactivation of motor brain regions if the actions were overtly or covertly
      performed during encoding. Compared to a verbal condition, encoding by means of
      overt as well as covert activity was associated with differential activity in
      regions in contralateral somatosensory and motor cortex. Several of these regions
      were reactivated during retrieval. Common to both the overt and covert conditions
      was reactivation of regions in left ventral motor cortex and left inferior
      parietal cortex. A direct comparison of the overt and covert activity conditions
      showed that activation and reactivation of left dorsal parietal cortex and right
      cerebellum was specific to the overt condition. These results support the
      reactivation hypothesis by showing that verbal-explicit memory of actions
      involves areas that are engaged during overt and covert motor activity.

PMID- 11467925
TI  - Low-lying excited states of proteins revealed from nonlinear pressure shifts in
      1H and 15N NMR.

PMID- 11467926
TI  - Binding of annexin V to membrane products of lipid peroxidation.
AB  - There is increasing evidence that endogenously generated aldehydes formed as a
      result of lipid peroxidation are involved in the pathophysiological effects
      associated with oxidative stress in cells and tissues. Malondialdehyde (MDA), a
      major product of lipid peroxidation, can modify amines present on the cell
      surface and thereby introduce negative charges that can affect the interfacial
      ionic layer. We show that lipid peroxidation of RBC generates MDA adducts that,
      similar to phosphatidylserine (PS), bind annexin V in a Ca(2+)-dependent manner.
      Like PS, these adducts also promote the "PS-dependent" prothrombinase assays,
      albeit to lower levels. These results indicate that annexin V binding cannot be
      used as an exclusive indicator of cell surface PS and raise the possibility that
      some phenomenon attributed to PS may, in fact, also involve aldehyde-lipid
      adducts.

PMID- 11467927
TI  - Nuclear magnetic resonance in the era of structural genomics.
AB  - Current interests in structural genomics, and the associated need for high
      through-put structure determination methods, offer an opportunity to examine new
      nuclear magnetic resonance (NMR) methodology and the impact this methodology can
      have on structure determination of proteins. The time required for structure
      determination by traditional NMR methods is currently long, but improved
      hardware, automation of analysis, and new sources of data such as residual
      dipolar couplings promise to change this. Greatly improved efficiency, coupled
      with an ability to characterize proteins that may not produce crystals suitable
      for investigation by X-ray diffraction, suggests that NMR will play an important
      role in structural genomics programs.

PMID- 11467928
TI  - Role of hydrogen bonding interactions to N(3)H of the flavin mononucleotide
      cofactor in the modulation of the redox potentials of the Clostridium
      beijerinckii flavodoxin.
AB  - The role of the hydrogen bonding interaction with the N(3)H of the flavin
      cofactor in the modulation of the redox properties of flavoproteins has not been
      extensively investigated. In the flavodoxin from Clostridium beijerinckii, the
      gamma-carboxylate group of glutamate-59 serves as a dual hydrogen bond acceptor
      with the N(3)H of flavin mononucleotide (FMN) cofactor and the amide hydrogen of
      the adjacent polypeptide backbone in all three oxidation states. This "bridging"
      interaction serves to anchor the FMN in the binding site, which, based on the
      E59Q mutant, indirectly affects the stability of the neutral flavin semiquinone
      by facilitating a strong and critical interaction at the FMN N(5)H [Bradley, L.
      H., and Swenson, R. P. (1999) Biochemistry 38, 12377-12386]. In this study, the
      specific role of the N(3)H interaction itself was investigated through the
      systematic replacement of Glu59 by aspartate, asparagine, and alanine in an
      effort to weaken, disrupt, and/or eliminate this interaction, respectively. Just
      as for the E59Q mutant, each replacement significantly weakened the binding of
      the cofactor, particularly for the semiquinone state, affecting the midpoint
      potentials of each one-electron couple in opposite directions. (1)H-(15)N HSQC
      nuclear magnetic resonance (NMR) spectroscopic studies revealed that not only was
      the N(3)H interaction weakened as anticipated, but so also was the hydrogen
      bonding interaction with the N(5)H. Using the temperature coefficients of the
      N(5)H to quantify and correct for changes in this interaction, the contribution
      of the N(3)H hydrogen bond to the binding of each redox state of the FMN was
      isolated and estimated. Based on this analysis, the N(3)H hydrogen bonding
      interaction appears to contribute primarily to the stability of the oxidized
      state (by as much as 2 kcal/mol) and to a lesser extent the reduced states. It is
      concluded that this interaction contributes only modestly (<45 mV) to the
      modulation of the midpoint potential for each redox couple in the flavodoxin.
      These conclusions are generally consistent with ab initio calculations and model
      studies on the non-protein-bound cofactor.

PMID- 11467929
TI  - A structural account of substrate and inhibitor specificity differences between
      two naphthol reductases.
AB  - Two short chain dehydrogenase/reductases mediate naphthol reduction reactions in
      fungal melanin biosynthesis. An X-ray structure of 1,3,6,8
      tetrahydroxynaphthalene reductase (4HNR) complexed with NADPH and pyroquilon was
      determined for examining substrate and inhibitor specificities that differ from
      those of 1,3,8-trihydroxynaphthalene reductase (3HNR). The 1.5 A resolution
      structure allows for comparisons with the 1.7 A resolution structure of 3HNR
      complexed with the same ligands. The sequences of the two proteins are 46%
      identical, and they have the same fold. The 30-fold lower affinity of the 4HNR
      NADPH complex for pyroquilon (a commercial fungicide that targets 3HNR) in
      comparison to that of the 3HNR-NADPH complex can be explained by unfavorable
      interactions between the anionic carboxyl group of the C-terminal Ile282 of 4HNR
      and CH and CH(2) groups of the inhibitor that are countered by favorable
      inhibitor interactions with 3HNR. 1,3,8-Trihydroxynaphthalene (3HN) and 1,3,6,8
      tetrahydroxynaphthalene (4HN) were modeled onto the cyclic structure of
      pyroquilon in the 4HNR-NADPH-pyroquilon complex to examine the 300-fold
      preference of the enzyme for 4HN over 3HN. The models suggest that the C-terminal
      carboxyl group of Ile282 has a favorable hydrogen bonding interaction with the C6
      hydroxyl group of 4HN and an unfavorable interaction with the C6 CH group of 3HN.
      Models of 3HN and 4HN in the 3HNR active site suggest a favorable interaction of
      the sulfur atom of the C-terminal Met283 with the C6 CH group of 3HN and an
      unfavorable one with the C6 hydroxyl group of 4HN, accounting for the 4-fold
      difference in substrate specificities. Thus, the C-terminal residues of the two
      naphthol reductase are determinants of inhibitor and substrate specificities.

PMID- 11467930
TI  - Synergistic interactions of multiple mutations on catalysis during the
      hydroxylation reaction of p-hydroxybenzoate hydroxylase: studies of the
      Lys297Met, Asn300Asp, and Tyr385Phe mutants reconstituted with 8-Cl-flavin.
AB  - The oxygen transfer to p-hydroxybenzoate catalyzed by p-hydroxybenzoate
      hydroxylase (PHBH) has been shown to occur via a C4a-hydroperoxide of the flavin.
      Two factors are likely to be important in facilitating the transfer of oxygen
      from the C4a-hydroperoxide to the substrate. (a) The positive electrostatic
      potential of the active site partially stabilizes the negative charge centered on
      the oxygen of the flavin-C4a-alkoxide leaving group during the transition state
      [Ortiz-Maldonado, M., Ballou, D. P., and Massey, V. (1999) Biochemistry 38, 8124
      8137]. (b) The hydrogen-bonding network ionizes the substrate to promote its
      nucleophilic attack on the electrophilic C4a-hydroperoxide intermediate [Entsch,
      B., Palfey, B. A., Ballou, D. P., and Massey, V. (1991) J. Biol. Chem. 266, 17341
      17349]. This ionization is also aided by the positive electrostatic potential of
      the active site [Moran, G. R., Entsch, B., Palfey, B. A., and Ballou, D. P.
      (1997) Biochemistry 36, 7548-7556]. Substituents on the flavin can specifically
      affect the stability of the alkoxide leaving-group, whereas changes to specific
      enzyme residues can affect the charge in the active site and the hydrogen-bonding
      network. We have used wild-type (WT) PHBH and several mutant forms, all with
      normal FAD and with 8-Cl-FAD substituted for FAD, to assess the relative
      contributions of the two effects. Lys297Met and Asn300Asp have decreased positive
      charge in the active site, and these variants engender approximately 35-fold
      slower hydroxylation rates than the WT enzyme. Substitution of 8-Cl-FAD in these
      mutant forms gives approximately 1.8-fold increases in hydroxylation rates,
      compared with a > or =4.8-fold increase for WT with this flavin. The
      hydroxylation catalyzed by Tyr385Phe, a mutant enzyme form with a disrupted
      hydrogen-bonding network that compromises the ionization of the substrate without
      changing the positive charge of the active site, is stimulated 1.5-fold by
      substituting the enzyme with 8-Cl-FAD. The substrate, tetrafluoro-p
      hydroxybenzoate, is fully ionized in WT PHBH, but this phenolate is a poor
      nucleophile because of the electron-withdrawing effects of the fluorine
      substituents. With tetrafluoro-p-hydroxybenzoate as the substrate, substitution
      of FAD with 8-Cl-FAD in the WT enzyme stabilizes the leaving alkoxide and leads
      to a 2.3-fold increase in the hydroxylation rate compared to that with FAD.
      Either the use of substrates that do not communicate with the proton network or
      the mutation of amino acid residues that perturb this interaction may prevent a
      necessary conformational change that allows proper orientation between reactants
      during the hydroxylation reaction or permits the essential protonation of the
      initially formed nascent flavin-C4a-peroxide anion. Thus, both activation of
      substrate by the proton network and stabilization of the leaving alkoxide appear
      to be important for oxygen transfer catalyzed by PHBH. The full effect of the
      substituents on the flavin (4.8-fold) can only be realized when the optimal
      transition state can be achieved, and this optimal state is not fully realized
      with the mutant forms.

PMID- 11467931
TI  - Solution structure of 2-(pyrido[1,2-e]purin-4-yl)amino-ethanol intercalated in
      the DNA duplex d(CGATCG)2.
AB  - The solution structure of the complex formed between d(CGATCG)(2) and 2
      (pyrido[1,2-e]purin-4-yl)amino-ethanol, a new antitumor drug under design, has
      been resolved using NMR spectroscopy and restrained molecular dynamic
      simulations. The drug molecule intercalates between each of the CpG dinucleotide
      steps with its side chain lying in the minor groove. Analysis of NMR data
      establishes a weak stacking interaction between the intercalated ligand and the
      DNA bases; however, the drug/DNA affinity is enhanced by a hydrogen bond between
      the hydroxyl group of the end of the intercalant side chain and the amide group
      of guanine G6. Unrestrained molecular dynamic simulations performed in a water
      box confirm the stability of the intercalation model. The structure of the
      intercalated complex enables insight into the structure-activity relationship,
      allowing rationalization of the design of new antineoplasic agents.

PMID- 11467932
TI  - Long-range oxidative damage in DNA/RNA duplexes.
AB  - Oxidative damage as a result of DNA-mediated long-range charge transport occurs
      readily and at high yield in duplex DNA, and it is of interest whether similar
      damage can occur in duplex oligonucleotides that include both ribo- and
      deoxyribonucleotides. Assemblies containing RNA and mixed RNA.DNA strands were
      constructed containing tethered ethidium as a photooxidant. In photooxidation
      experiments, long-range oxidative damage to the ribose-containing strand of the
      oligonucleotide duplexes was examined. Hole injection by photoexcited ethidium
      followed by radical migration to oxidatively susceptible guanines afforded
      significant damage on ribose-containing strands at long range ( approximately 35
      A). This damage does not differ substantially in yield and location from that
      found in B-DNA duplexes. No oxidative damage was found upon photooxidation of
      DNA/RNA duplexes containing tethered metallointercalator, despite the ability of
      the rhodium complex to promote oxidative damage at a distance in DNA duplexes.
      This result is attributed to the poor coupling of the rhodium complex into the A
      like RNA/DNA duplex. The ability for long-range charge transport to occur in
      double-stranded nucleic acids of different comformations is considered in light
      of modeling studies that show interstrand base-base overlap between the opposing,
      complementary strands that make up RNA/DNA hybrid duplexes. Thus, the possibility
      of long-range radical migration to effect oxidative damage or signaling may be
      considered also in the context of transcriptional events.

PMID- 11467933
TI  - Multiple cleavage activities of endonuclease V from Thermotoga maritima:
      recognition and strand nicking mechanism.
AB  - Endonuclease V is a deoxyinosine 3'-endonuclease which initiates removal of
      inosine from damaged DNA. A thermostable endonuclease V from the
      hyperthermophilic bacterium Thermotoga maritima has been cloned and expressed in
      Escherichia coli. The DNA recognition and reaction mechanisms were probed with
      both double-stranded and single-stranded oligonucleotide substrates which
      contained inosine, abasic site (AP site), uracil, or mismatches. Gel mobility
      shift and kinetic analyses indicate that the enzyme remains bound to the cleaved
      inosine product. This slow product release may be required in vivo to ensure an
      orderly process of repairing deaminated DNA. When the enzyme is in excess, the
      primary nicked products experience a second nicking event on the complementary
      strand, leading to a double-stranded break. Cleavage at AP sites suggests that
      the enzyme may use a combination of base contacts and local distortion for
      recognition. The weak binding to uracil sites may preclude the enzyme from
      playing a significant role in repair of such sites, which may be occupied by
      uracil-specific DNA glycosylases. Analysis of cleavage patterns of all 12 natural
      mismatched base pairs suggests that purine bases are preferrentially cleaved,
      showing a general hierarchy of A = G > T > C. A model accounting for the
      recognition and strand nicking mechanism of endonuclease V is presented.

PMID- 11467934
TI  - 3'-5' Exonucleolytic activity of DNA polymerases: structural features that allow
      kinetic discrimination between ribo- and deoxyribonucleotide residues.
AB  - We have determined rates for the excision of nucleotides from the 3' termini of
      chimeric DNA-RNA oligonucleotides using the Klenow fragment (KF) and two other
      DNA polymerases, from phages T4 and T7. For these studies, we synthesized DNA-RNA
      chimeric oligonucleotides with RNA residues in defined positions. When a
      ribonucleotide residue was placed at the 3' terminus, all three DNA polymerases
      removed it at the same rate as they did for substrates composed solely of
      deoxynucleotide residues. There was a decrease in the excision rate, however,
      when a ribonucleotide residue was located at the second or third position from
      the 3' terminus. When both the second and third positions were occupied by
      ribonucleotide residues, the excision rate for the 3' terminal nucleotide was
      reduced even further and was almost identical to the rate observed when the DNA
      polymerases encountered single-stranded RNA. The magnitude of the effect of
      ribonucleotide residues on the excision rate was lower when Mn(2+) replaced
      Mg(2+) as the essential divalent cation. Two KF mutations, Y423A and N420A,
      selectively affected the excision rates for the chimeric substrates.
      Specifically, Y423A totally abolished the rate reduction when there was a single
      ribonucleotide residue immediately preceding the 3' terminus, whereas N420A
      diminished, but did not eliminate, the rate reduction relative to that of wild
      type KF when the single ribonucleotide residue occupied either the second or
      third position from the 3' terminus. These results are consistent with the
      structure of a KF-ss DNA complex from which it can be deduced, by modeling, that
      a 2' OH group on the second sugar from the 3' terminus would sterically clash
      with the Tyr 423 side chain, and a 2' OH group on the third sugar would clash
      with the side chain of Asn 420. The corresponding mutations in T4 DNA polymerase
      did not affect the rate of hydrolysis of the chimeric oligonucleotides. Thus,
      there appears to be a major difference in the kinetic behavior of KF and T4 DNA
      polymerase with respect to the exonuclease reaction. These results are discussed
      with respect to their possible biological relevance to DNA replication.

PMID- 11467935
TI  - Structural analyses of nucleotide binding to an aminoglycoside
      phosphotransferase.
AB  - 3',5"-Aminoglycoside phosphotransferase type IIIa [APH(3')-IIIa] is a bacterial
      enzyme that confers resistance to a range of aminoglycoside antibiotics while
      exhibiting striking homology to eukaryotic protein kinases (ePK). The structures
      of APH(3')-IIIa in its apoenzyme form and in complex with the nonhydrolyzable ATP
      analogue AMPPNP were determined to 3.2 and 2.4 A resolution, respectively.
      Furthermore, refinement of the previously determined ADP complex was completed.
      The structure of the apoenzyme revealed alternate positioning of a flexible loop
      (analogous to the P-loop of ePK's), occupying part of the nucleotide-binding
      pocket of the enzyme. Despite structural similarity to protein kinases, there was
      no evidence of domain movement associated with nucleotide binding. This rigidity
      is due to the presence of more extensive interlobe interactions in the APH(3')
      IIIa structure than in the ePK's. Differences between the ADP and AMPPNP
      complexes are confined to the area of the nucleotide-binding pocket. The position
      of conserved active site residues and magnesium ions remains unchanged, but there
      are differences in metal coordination between the two nucleotide complexes.
      Comparison of the di/triphosphate binding site of APH(3')-IIIa with that of ePK's
      suggests that the reaction mechanism of APH(3")-IIIa and related aminoglycoside
      kinases will closely resemble that of eukaryotic protein kinases. However, the
      orientation of the adenine ring in the binding pocket differs between APH(3')
      IIIa and the ePK's by a rotation of approximately 40 degrees. This alternate
      binding mode is likely a conserved feature among aminoglycoside kinases and could
      be exploited for the structure-based drug design of compounds to combat
      antibiotic resistance.

PMID- 11467936
TI  - Independent Lec1A CHO glycosylation mutants arise from point mutations in N
      acetylglucosaminyltransferase I that reduce affinity for both substrates.
      Molecular consequences based on the crystal structure of GlcNAc-TI.
AB  - A key enzyme in regulating the maturation of N-linked glycans is UDP-N
      acetylglucosamine:alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I
      (GlcNAc-TI, EC 2.4.1.101). Lec1 CHO cells lack GlcNAc-TI activity and synthesize
      only the oligomannosyl class of N-glycans. By contrast, Lec1A CHO mutants have
      weak GlcNAc-TI activity due to the reduced affinity of GlcNAc-TI for both the UDP
      GlcNAc and Man(5)GlcNAc(2)Asn substrates. Lec1A CHO mutants synthesize hybrid and
      complex N-glycans, albeit in reduced amounts compared to parental CHO cells. In
      this paper, we identify two point mutations that gave rise to the Lec1A phenotype
      in three independent Lec1A CHO mutants. The G634A mutation in Lec1A.2C converts
      an aspartic acid to an asparagine at amino acid 212, disrupting a conserved DXD
      motif (E(211)DD(213) in all GlcNAc-TIs) that makes critical interactions with
      bound UDP-GlcNAc and Mn(2+) ion in rabbit GlcNAc-TI. The C907T mutation in
      Lec1A.3E and Lec1A.5J converts an arginine conserved in all GlcNAc-TIs to a
      tryptophan at amino acid 303, altering interactions that are important in
      stabilizing a critical structural element in rabbit GlcNAc-TI. Correction of each
      mutation by site-directed mutagenesis restored their GlcNAc-TI activity and
      lectin binding properties to parental levels. The effect of the two amino acid
      changes on GlcNAc-TI catalysis is discussed in relation to the crystal structure
      of rabbit GlcNAc-TI complexed with manganese and UDP-GlcNAc.

PMID- 11467937
TI  - Tryptophan residues at subunit interfaces used as fluorescence probes to
      investigate homotropic and heterotropic regulation of aspartate transcarbamylase.
AB  - The homotropic and heterotropic interactions in Escherichia coli aspartate
      transcarbamylase (EC 2.1.3.2) are accompanied by various structure modifications.
      The large quaternary structure change associated with the T to R transition,
      promoted by substrate binding, is accompanied by different local conformational
      changes. These tertiary structure modifications can be monitored by fluorescence
      spectroscopy, after introduction of a tryptophan fluorescence probe at the site
      of investigation. To relate unambiguously the fluorescence signals to structure
      changes in a particular region, both naturally occurring Trp residues in
      positions 209c and 284c of the catalytic chains were previously substituted with
      Phe residues. The regions of interest were the so-called 240's loop at position
      Tyr240c, which undergoes a large conformational change upon substrate binding,
      and the interface between the catalytic and regulatory chains in positions
      Asn153r and Phe145r supposed to play a role in the different regulatory
      processes. Each of these tryptophan residues presents a complex fluorescence
      decay with three to four independent lifetimes, suggesting that the holoenzyme
      exists in slightly different conformational states. The bisubstrate analogue N
      phosphonacetyl-L-aspartate affects mostly the environment of tryptophans at
      position 240c and 145r, and the fluorescence signals were related to ligand
      binding and the quaternary structure transition, respectively. The binding of the
      nucleotide activator ATP slightly affects the distribution of the conformational
      substates as probed by tryptophan residues at position 240c and 145r, whereas the
      inhibitor CTP modifies the position of the C-terminal residues as reflected by
      the fluorescence properties of Trp153r. These results are discussed in
      correlation with earlier mutagenesis studies and mechanisms of the enzyme
      allosteric regulation.

PMID- 11467938
TI  - The crystallographic structure of the B800-820 LH3 light-harvesting complex from
      the purple bacteria Rhodopseudomonas acidophila strain 7050.
AB  - The B800-820, or LH3, complex is a spectroscopic variant of the B800-850 LH2
      peripheral light-harvesting complex. LH3 is synthesized by some species and
      strains of purple bacteria when growing under what are generally classed as
      "stressed" conditions, such as low intensity illumination and/or low temperature
      (<30 degrees C). The apoproteins in these complexes modify the absorption
      properties of the chromophores to ensure that the photosynthetic process is
      highly efficient. The crystal structure of the B800-820 light-harvesting complex,
      an integral membrane pigment-protein complex, from the purple bacteria
      Rhodopseudomonas (Rps.) acidophila strain 7050 has been determined to a
      resolution of 3.0 A by molecular replacement. The overall structure of the LH3
      complex is analogous to that of the LH2 complex from Rps. acidophila strain
      10050. LH3 has a nonameric quaternary structure where two concentric cylinders of
      alpha-helices enclose the pigment molecules bacteriochlorophyll a and carotenoid.
      The observed spectroscopic differences between LH2 and LH3 can be attributed to
      differences in the primary structure of the apoproteins. There are changes in
      hydrogen bonding patterns between the coupled Bchla molecules and the protein
      that have an effect on the conformation of the C3-acetyl groups of the B820
      molecules. The structure of LH3 shows the important role that the protein plays
      in modulating the characteristics of the light-harvesting system and indicates
      the mechanisms by which the absorption properties of the complex are altered to
      produce a more efficient light-harvesting component.

PMID- 11467939
TI  - Structural studies of a neuropeptide precursor protein with an RGD proteolytic
      site.
AB  - The snail Lymnaea stagnalis produces a neuropeptide precursor protein that
      contains seven Arg-Gly-Asp (RGD) sites. These sites are recognized and cleaved by
      one or more prohormone convertases in the first processing step to yield mature
      neuropeptides in the secretory pathway. Conformations of two synthetic RGD
      containing peptides derived from the L. stagnalis precursor protein were
      determined by NMR spectroscopy. The peptides were tested in a platelet
      aggregation assay for RGD activity and were processed in vitro by PC2 and furin.
      The native peptide with a proline following the RGD site has minimal structure
      around the RGD region, does not inhibit platelet aggregation, and is properly
      processed by the enzymes PC2 and furin. A variant of the native fragment with a
      serine following the RGD sequence has a significant amount of a reverse turn
      around the RGD region, is a potent inhibitor of platelet aggregation, and is
      processed with the same specificity as the native fragment. The large
      conformational differences between the two peptides provide a molecular mechanism
      for effects of proline residues following the RGD site and suggest that precursor
      processing is influenced more by flexibility than by the conformation of the
      processing site.

PMID- 11467940
TI  - Membrane interactions of mutated forms of the influenza fusion peptide.
AB  - We have studied a group of fusion peptides of influenza hemagglutinin in which
      the N-terminal amino acid, Gly (found in the wild-type peptide), has been
      systematically substituted with Ala, Ser, Val, or Glu. The activity of the intact
      hemagglutinin protein with these same substitutions has already been reported. As
      a measure of the extent of modulation of intrinsic membrane curvature by these
      peptides, we determined their effects on the polymorphic phase transition of
      dipalmitoleoylphosphatidylethanolamine. The wild-type peptide is the only one
      that, at pH 5, can substantially decrease the temperature of this transition.
      This is also the only form in which the intact protein promotes contents mixing
      in cells. The Ala and Ser mutant hemagglutinins exhibit a hemifusion phenotype,
      and their fusion peptides have little effect on lipid polymorphism at low pH. The
      two mutant proteins that are completely fusion inactive are the Val and Glu
      mutant hemagglutinins. The fusion peptides from these forms significantly
      increase the polymorphic phase transition temperature at low pH. We find that the
      effect of the fusion peptides on membrane curvature, as monitored by a shift in
      the temperature of this polymorphic phase transition, correlates better with the
      fusogenic activities of the corresponding protein than do measurements of the
      isotropic (31)P NMR signals or the ability to induce the fusion of liposomes. The
      inactivity of the hemagglutinin protein with the hydrophobic Val mutation can be
      explained by the change in the angle of membrane insertion of the helical fusion
      peptide as measured by polarized FTIR. Thus, the nature of the interactions of
      the fusion peptides with membranes can, in large part, explain the differences in
      the fusogenic activity of the intact protein.

PMID- 11467941
TI  - Ca2+ binding site 2 in calcineurin-B modulates calmodulin-dependent calcineurin
      phosphatase activity.
AB  - Calcineurin is the Ca(2+)- and calmodulin-dependent Ser/Thr phosphatase. Human
      calcineurin-Aalpha and wild-type or mutated calcineurin-Bs were coexpressed in
      Escherichia coli and purified by calmodulin-Sepharose affinity chromatography.
      Four calcineurin-B mutants were studied. Each had a single conserved Glu in the
      12th position of one EF-hand Ca(2+) binding site replaced by a Lys, resulting in
      the loss of Ca(2+) binding to that site. Phosphatase activities of the enzymes
      toward a (32)P-labeled phosphopeptide substrate were measured. Inactivating
      Ca(2+) binding sites 1, 2, or 3 in calcineurin-B reduced Ca(2+)-dependent
      phosphatase activity of the enzymes in the absence of calmodulin with the site 2
      mutation being most effective. Inactivating Ca(2+) binding site 4 did not change
      enzyme activity or sensitivity to Ca(2+) in either the absence or presence of
      calmodulin. The calmodulin-dependent phosphatase activity of the enzymes
      containing site 1, 2, or 3 mutations in calcineurin-B was also decreased compared
      to enzyme with wild-type calcineurin-B. Of these enzymes, the one with the site 2
      mutation was most profoundly affected as determined by the magnitude of the shift
      in Ca(2+) concentration dependence. Binding of a fluorescein-labeled calmodulin
      to the wild-type and the site 2 mutant enzymes was examined using fluorescence
      polarization measurements. The decrease in Ca(2+) sensitivity for the enzyme with
      calcineurin-B site 2 inactivated is apparently due to a decrease in the affinity
      of that enzyme for calmodulin at low Ca(2+) concentrations. These data support a
      role for Ca(2+) binding site 3 in the carboxyl half of calcineurin-B in
      transmitting the Ca(2+) signal to calcineurin-A and indicate that site 2 in the
      amino half of calcineurin-B is critical for enzyme activation.

PMID- 11467942
TI  - Membrane-anchoring interactions of M13 major coat protein.
AB  - The response to hydrophobic mismatch of membrane-bound M13 major coat protein is
      measured using site-directed fluorescence and ESR spectroscopy. For this purpose,
      we investigate the membrane-anchoring interactions of M13 coat protein in model
      systems consisting of phosphatidylcholine bilayers that vary in hydrophobic
      thickness. Mutant coat proteins are prepared with an AEDANS-labeled single
      cysteine residue in the hinge region of the protein or at the C-terminal side of
      the transmembrane helix. In addition, the fluorescence of the tryptophan residue
      is studied as a monitor for the N-terminal side of the transmembrane helix. The
      fluorescence results show that the hinge region and C-terminal side of the
      transmembrane helix hardly respond to hydrophobic mismatch. In contrast, the N
      terminal side of the helical transmembrane domain shifts to a more apolar
      environment, when the hydrophobic thickness is increased. The apparent strong
      membrane-anchoring interactions of the C-terminus are confirmed using a mutant
      that contains a longer transmembrane domain. As a result of this mutation, the
      tryptophan residue at the N-terminal side of the helical domain clearly shifts to
      a more polar environment, whereas the labeled position 46 at the C-terminal side
      is not affected. The phenylalanines in the C-terminal part of the protein play an
      important role in these apparent strong anchoring interactions. This is
      demonstrated with a mutant in which both phenylalanines are replaced by alanine
      residues. The phenylalanine residues in the C-terminus affect the location in the
      membrane of the entire transmembrane domain of the protein.

PMID- 11467943
TI  - The secondary structure of the inhibited mitochondrial ADP/ATP transporter from
      yeast analyzed by FTIR spectroscopy.
AB  - Fourier transform infrared spectroscopy has been applied to the study of the
      carboxyatractyloside-inhibited mitochondrial ADP/ATP transporter from the yeast
      Saccharomyces cerevisiae, either solubilized in dodecyl maltoside or
      reconstituted in phosphatidylcholine liposomes. Its secondary structure has been
      estimated by means of Fourier self-deconvolution followed by curve fit. A Voigt
      function was used to fit the components of the deconvoluted spectrum, aiming to
      account for any distortions introduced by deconvolution. For any of the states
      analyzed, reconstituted or solubilized, in solution or in dry films, 60-70% of
      the amino acids are found to adopt alpha-helix plus unordered structures,
      coherent with the six transmembrane spanning helix model. Moreover, the problem
      of structure preservation on drying was addressed, and several observations
      pointed to a maintenance of the protein structure in dry films. Comparison of
      reconstituted and solubilized samples indicated the presence of both lipid
      induced changes in the protein (decrease of the beta-sheets and increase of
      unordered structures) and protein-induced changes in the lipids (strong hydrogen
      bonding of lipid C=O groups). To obtain a better discrimination of alpha-helix
      and unordered structure contributions for the reconstituted form, H/D exchange
      experiments were performed. Between 35% and 45% of the amino acids were finally
      assigned to alpha-helix structures, compatible with the existence of five or six
      transmembrane spanning helices in the transporter. The level of H/D exchange was
      determined after 15 h of exposure to D(2)O vapor to be 85%, reflecting a high
      accessibility of the amide hydrogens even for the carboxyatractyloside-inhibited
      state.

PMID- 11467944
TI  - Detection of disulfide bonds in bovine brain tubulin and their role in protein
      folding and microtubule assembly in vitro: a novel disulfide detection approach.
AB  - Cysteine residues in tubulin are actively involved in regulating ligand
      interactions and microtubule formation both in vivo and in vitro. These cysteine
      residues are sensitive reporters in determining the conformation of tubulin.
      Although some of the cysteines are critical in modulating drug binding and
      microtubule assembly, it is not clear how many of these normally exist as
      disulfides. The controversy regarding the disulfide bonds led us to develop a
      disulfide detection assay to reexamine the presence of the disulfide linkages in
      purified alphabeta tubulin and explore their possible biological functions in
      vitro. The accessible cysteine residues in alphabeta tubulin were alkylated with
      an excess of iodoacetamide to prevent artifactual generation of disulfide
      linkages in tubulin. After removal of excess iodoacetamide, tubulin was unfolded
      in 8 M urea. Half of the unfolded tubulin was treated with dithiothreitol to
      reduce any disulfide bonds present. The aliquots were then treated with
      iodo[(14)C]acetamide and the incorporation of radioactivity was measured. We also
      used the same approach to detect the disulfide linkages in the tubulin in a whole
      cell extract. We found in both cases that the samples which were not treated with
      dithiothreitol had little or no incorporation of iodo[(14)C]acetamide, while the
      others that were treated with dithiothreitol had significant amounts of (14)C
      incorporation into tubulin. Moreover, the reduction of the disulfide linkages in
      tubulin resulted in inhibition of microtubule assembly (29-54%) and markedly
      affected refolding of the tubulin from both an intermediate and a completely
      unfolded state. All these data therefore suggest that tubulin has intrachain
      disulfide bonds in the alpha- and beta-subunits and that these disulfides assist
      in correct refolding of tubulin from the intermediate unfolded state or help to
      recover the hydrophobic domains from the completely unfolded state. These
      disulfides also regulate microtubule assembly and the stability of tubulin in
      vitro. Our results suggest that tubulin disulfides may play a role in tubulin
      folding and that thiol-disulfide exchange in tubulin could be a key regulator in
      microtubule assembly and dynamics of tubulin in vivo.

PMID- 11467945
TI  - Modulation of Na,K-ATPase and Na-ATPase activity by phospholipids and
      cholesterol. I. Steady-state kinetics.
AB  - The effects of phospholipid acyl chain length (n(c)), degree of acyl chain
      saturation, and cholesterol on Na,K-ATPase reconstituted into liposomes of
      defined lipid composition are described. The optimal acyl chain length of
      monounsaturated phosphatidylcholine in the absence of cholesterol was found to be
      22 but decreased to 18 in the presence of 40 mol % cholesterol. This indicates
      that the hydrophobic matching of the lipid bilayer and the transmembrane
      hydrophobic core of the membrane protein is a crucial parameter in supporting
      optimal Na,K-ATPase activity. In addition, the increased bilayer order induced by
      both cholesterol and saturated phospholipids could be important for the
      conformational mobility of the Na,K-ATPase changing the distribution of
      conformations. Lipid fluidity was important for several parameters of
      reconstitution, e.g., the amount of protein inserted and the orientation in the
      liposomes. The temperature dependence of the Na,K-ATPase as well of the Na-ATPase
      reactions depends both on phospholipid acyl chain length and on cholesterol.
      Cholesterol increased significantly both the enthalpy of activation and entropy
      of activation for Na,K-ATPase activity and Na-ATPase activity of Na,K-ATPase
      reconstituted with monounsaturated phospholipids. In the presence of cholesterol
      the free energy of activation was minimum at a lipid acyl chain length of 18, the
      same that supported maximum turnover. In the case of ATPase reconstituted without
      cholesterol, the minimum free energy of activation and the maximum turnover both
      shifted to longer acyl chain lengths of about 22.

PMID- 11467946
TI  - Purified protein S contains multimeric forms with increased APC-independent
      anticoagulant activity.
AB  - Protein S, the cofactor of activated protein C (APC), also expresses
      anticoagulant activity independent of APC by directly inhibiting prothrombin
      activation via interactions with factor Xa, factor Va, and phospholipids. In
      different studies, however, large variations in APC-independent anticoagulant
      activities have been reported for protein S. The investigation presented here
      shows that within purified protein S preparations different forms of protein S
      are present, of which a hitherto unrecognized form (<5% of total protein S) binds
      with high affinity to phospholipid bilayers (K(d) < 1 nM). The remaining protein
      S (>95%) has a low affinity (K(d) = 250 nM) for phospholipids. Using their
      different affinities for phospholipids, separation of the forms of protein S was
      achieved. Native polyacrylamide gel electrophoresis demonstrated that the form of
      protein S that binds to phospholipids with low affinity migrated as a single
      band, whereas the high-affinity protein S exhibited several bands that migrated
      with reduced mobility. Size-exclusion chromatography revealed that the slower
      migrating bands represented multimeric forms of protein S. Multimeric protein S
      (<5% of total protein S) appeared to have a 100-fold higher APC-independent
      anticoagulant activity than the abundant form of protein S. Comparison of
      purified protein S preparations that exhibited a 4-fold difference in APC
      independent anticoagulant activity showed that the ability to inhibit prothrombin
      activation correlated with the content of multimeric protein S. Multimeric
      protein S could not be identified in normal human plasma, and it is therefore
      unlikely that this form of protein S contributes to the APC-independent
      anticoagulant activity of protein S that is observed in plasma.

PMID- 11467947
TI  - Mechanism of integrin activation by disulfide bond reduction.
AB  - Integrin alphaIIbbeta3 plays a pivotal role in hemostasis and thrombosis by
      mediating platelet adhesion and platelet aggregation. Integrin alphaIIbbeta3
      contains an on/off switch that regulates its ligand binding affinity. The switch
      from "off" to "on" is commonly referred to as integrin activation. We recently
      identified a redox site within the extracellular domain of the platelet integrin
      alphaIIbbeta3 that exhibits many properties that one might expect of the on/off
      switch [Yan, B., and Smith, J. W. (2000) J. Biol. Chem. 275, 39964-39972].
      Several independent reports show that reducing agents, such as dithiothreitol,
      can activate integrins. The objective of the present study was to determine if
      the effects of DTT can be attributed to a perturbation at the integrin redox
      site. Indeed, we find that DTT reduces two disulfide bonds within the integrin's
      cysteine-rich domain. Such bond reduction leads to global conformational changes
      within both alphaIIb and beta3 and the opening of the RGD and fibrinogen binding
      sites. These findings causally link the reduction of disulfide bonds within the
      integrin's redox site to transitions in the integrin's activation state.

PMID- 11467948
TI  - Glycoengineering of therapeutic glycoproteins: in vitro galactosylation and
      sialylation of glycoproteins with terminal N-acetylglucosamine and galactose
      residues.
AB  - Therapeutic glycoproteins produced in different host cells by recombinant DNA
      technology often contain terminal GlcNAc and Gal residues. Such glycoproteins
      clear rapidly from the serum as a consequence of binding to the mannose receptor
      and/or the asialoglycoprotein receptor in the liver. To increase the serum half
      life of these glycoproteins, we carried out in vitro glycosylation experiments
      using TNFR-IgG, an immunoadhesin molecule, as a model therapeutic glycoprotein.
      TNFR-IgG is a disulfide-linked dimer of a polypeptide composed of the
      extracellular portion of the human type 1 (p55) tumor necrosis factor receptor
      (TNFR) fused to the hinge and Fc regions of the human IgG(1) heavy chain. This
      bivalent antibody-like molecule contains four N-glycosylation sites per
      polypeptide, three in the receptor portion and one in the Fc. The heterogeneous N
      linked oligosaccharides of TNFR-IgG contain sialic acid (Sia), Gal, and GlcNAc as
      terminal sugar residues. To increase the level of terminal sialylation, we
      regalactosylated and/or resialylated TNFR-IgG using beta-1,4
      galactosyltransferase (beta1,4GT) and/or alpha-2,3-sialyltransferase
      (alpha2,3ST). Treatment of TNFR-IgG with beta1,4GT and UDP-Gal, in the presence
      of MnCl(2), followed by MALDI-TOF-MS analysis of PNGase F-released N-glycans
      showed that the number of oligosaccharides with terminal GlcNAc residues was
      significantly decreased with a concomitant increase in the number of terminal Gal
      residues. Similar treatment of TNFR-IgG with alpha2,3ST and CMP-sialic acid (CMP
      Sia), in the presence of MnCl(2), produced a molecule with an approximately 11%
      increase in the level of terminal sialylation but still contained
      oligosaccharides with terminal GlcNAc residues. When TNFR-IgG was treated with a
      combination of beta1,4GT and alpha2,3ST (either in a single step or in a stepwise
      fashion), the level of terminal sialylation was increased by approximately 20
      23%. These results suggest that in vitro galactosylation and sialylation of
      therapeutic glycoproteins with terminal GlcNAc and Gal residues can be achieved
      in a single step, and the results are similar to those for the stepwise reaction.
      This type of in vitro glycosylation is applicable to other glycoproteins
      containing terminal GlcNAc and Gal residues and could prove to be useful in
      increasing the serum half-life of therapeutic glycoproteins.

PMID- 11467949
TI  - Vgb from Staphylococcus aureus inactivates streptogramin B antibiotics by an
      elimination mechanism not hydrolysis.
AB  - The streptogramin antibiotics were identified almost 50 years ago but have only
      recently found clinical use as a consequence of the increase in multidrug
      resistant bacteria. Despite the fact that these antibiotics have historically not
      found intense clinical use, resistance to streptogramins exists. Streptogramins
      consist of a mixture of two components: cyclic polyunsaturated macrolactones
      (group A) and cyclic hexadepsipeptides (group B). The latter are cyclized through
      an ester bond between the hydroxyl group of an N-terminal threonine and the C
      terminal carboxyl. Resistance to the B streptogramins can occur through the
      production of enzymes such as Vgb from Staphylococcus aureus. This enzyme had
      been assumed to be a lactonase that inactivates the cyclic antibiotic by
      linearization through hydrolytic cleavage of the ester bond. We have expressed
      recombinant Vgb in quantity and, using a combination of mass spectrometry, NMR,
      and synthesis of model depsipeptides, show unequivocally that streptogramin B
      inactivation does not involve hydrolysis of the ester bond. Rather, the
      hexadepsipeptide is linearized through an elimination reaction across the ester
      bond generating an N-terminal dehydrobutyrine group. Therefore, Vgb is not a
      hydrolase but a lyase. We also have explored the activity of Vgb orthologues
      present in the chromosomes of various bacteria including Bordetella pertussis and
      Streptomyces coelicolor and have determined that these enzymes also show
      streptogramin B inactivation through an elimination mechanism indistinguishable
      to that used by Vgb. These results demonstrate that Vgb is a member of a large
      group of streptogramin B lyases that are present not only in resistant clinical
      isolates but also in the chromosomes of many bacteria. There is therefore a
      significant reservoir of streptogramin resistance enzymes in the environment,
      which has the potential to impact the long-term utility of these antibiotics.
      This research establishing the molecular mechanism of streptogramin resistance
      therefore has the potential to be exploited in the discovery of inhibitory
      compounds that could rescue antibiotic activity even in the presence of
      resistance elements.

PMID- 11467950
TI  - TFEC can function as a transcriptional activator of the nonmuscle myosin II heavy
      chain-A gene in transfected cells.
AB  - Transcription of the human nonmuscle myosin II heavy chain-A (NMHC-A) gene is
      regulated via multiple elements located in intron 1, including element F which
      contains an E-box. In this study we have identified and characterized the factors
      that are capable of binding to element F. Yeast one-hybrid screening using
      element F allowed isolation of cDNAs encoding transcriptional factors TFEC, TFE3,
      and USF2, each of which contains basic helix-loop-helix and leucine zipper
      motifs. Furthermore, cDNA cloning by polymerase chain reaction yielded cDNAs for
      two TFEC isoforms, designated TFEC-l and TFEC-s, which are generated by
      alternative pre-mRNA splicing. In addition to these four factors, USF1, which is
      known to share the same DNA binding elements with USF2, was isolated for
      comparison. Electrophoretic mobility shift assays and cotransfection studies of
      the expression constructs with reporter gene constructs revealed that the above
      five factors have different binding activities for element F with different
      transactivation potencies. USF1 and USF2 demonstrate the highest binding activity
      to element F, yet show the lowest element F-dependent transactivation. TFE3 has a
      high transactivation potency but the lowest binding activity. TFEC-l demonstrates
      a high binding activity with the highest transactivation potency, whereas TFEC-s
      has the same binding activity as TFEC-l with intermediate transactivation. We
      also demonstrate that an N-terminal activation domain exists only in TFEC-l,
      whereas a C-terminal activation domain is common to both the l and s isoforms.
      This study provides the first evidence of TFEC being an activator of
      transcription, with two separate activation domains.

PMID- 11467951
TI  - Imino proton exchange and base-pair kinetics in RNA duplexes.
AB  - Using NMR magnetization transfer from water and ammonia-catalyzed exchange of the
      imino proton, we have measured the base-pair lifetimes and the dissociation
      constants of six RNA duplexes: [r(CGCGAUCGCG)](2), [r(CGCGAAUUCGCG)](2),
      [r(CCUUUCGAAAGG)](2), [r(CGCACGUGCG)](2), [r(GGU(8)CC).r(GGA(8)CC)], and
      [poly(rA).poly(rU)], and we compare them with those of their DNA homologues. As
      predicted by a two-state (closed/open) model of the pair, the imino proton
      exchange times decrease linearly vs. the inverse of catalyst concentration. As in
      DNA duplexes, base pairs open one at a time, and the kinetics is in most cases
      insensitive to the nature of the adjacent residues. The lifetime of the r(G.C)
      pairs, 40 to 50 ms, is longer than that of the equivalent in the corresponding
      oligodeoxynucleotides, and the dissociation constants, about 10(-)(7), are
      slightly smaller. The r(A.U) opening and closing rates are much larger than those
      of the d(A.T) pairs, but the stabilities are comparable.

PMID- 11467952
TI  - Comparative binding energy analysis of the substrate specificity of haloalkane
      dehalogenase from Xanthobacter autotrophicus GJ10.
AB  - Comparative binding energy (COMBINE) analysis was conducted for 18 substrates of
      the haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 (DhlA): 1
      chlorobutane, 1-chlorohexane, dichloromethane, 1,2-dichloroethane, 1,2
      dichloropropane, 2-chloroethanol, epichlorohydrine, 2-chloroacetonitrile, 2
      chloroacetamide, and their brominated analogues. The purpose of the COMBINE
      analysis was to identify the amino acid residues determining the substrate
      specificity of the haloalkane dehalogenase. This knowledge is essential for the
      tailoring of this enzyme for biotechnological applications. Complexes of the
      enzyme with these substrates were modeled and then refined by molecular mechanics
      energy minimization. The intermolecular enzyme-substrate energy was decomposed
      into residue-wise van der Waals and electrostatic contributions and complemented
      by surface area dependent and electrostatic desolvation terms. Partial least
      squares projection to latent structures analysis was then used to establish
      relationships between the energy contributions and the experimental apparent
      dissociation constants. A model containing van der Waals and electrostatic
      intermolecular interaction energy contributions calculated using the AMBER force
      field explained 91% (73% cross-validated) of the quantitative variance in the
      apparent dissociation constants. A model based on van der Waals intermolecular
      contributions from AMBER and electrostatic interactions derived from the Poisson
      Boltzmann equation explained 93% (74% cross-validated) of the quantitative
      variance. COMBINE models predicted correctly the change in apparent dissociation
      constants upon single-point mutation of DhlA for six enzyme-substrate complexes.
      The amino acid residues contributing most significantly to the substrate
      specificity of DhlA were identified; they include Asp124, Trp125, Phe164, Phe172,
      Trp175, Phe222, Pro223, and Leu263. These residues are suitable targets for
      modification by site-directed mutagenesis.

PMID- 11467953
TI  - Identification of the high affinity Mn2+ binding site of bacteriophage lambda
      phosphoprotein phosphatase: effects of metal ligand mutations on electron
      paramagnetic resonance spectra and phosphatase activities.
AB  - Bacteriophage lambda phosphoprotein phosphatase (lambdaPP) has structural
      similarity to the mammalian Ser/Thr phosphoprotein phosphatases (PPPs) including
      the immunosuppressant drug target calcineurin. PPPs possess a conserved active
      site containing a dinuclear metal cluster, with metal ligands provided by a
      phosphoesterase motif plus two additional histidine residues at the C-terminus.
      Multiple sequence alignment of lambdaPP with 28 eubacterial and archeal
      phosphoesterases identified active site residues from the phosphoesterase motif
      and in many cases 2 additional C-terminal His metal ligands. Most highly similar
      to lambdaPP are E. coli PrpA and PrpB. Using the crystal structure of lambdaPP
      [Voegtli, W. C., et al. (2000) Biochemistry 39, 15365-15374] as a structural and
      active site model for PPPs and related bacterial phosphoesterases, we have
      studied mutant forms of lambdaPP reconstituted with Mn(2+) by electron
      paramagnetic resonance (EPR) spectroscopy, Mn(2+) binding analysis, and
      phosphatase kinetics. Analysis of Mn(2+)-bound active site mutant lambdaPP
      proteins shows that H22N, N75H, and H186N mutations decrease phosphatase activity
      but still allow mononuclear Mn(2+) and [(Mn(2+))(2)] binding. The high affinity
      Mn(2+) binding site is shown to consist of M2 site ligands H186 and Asn75, but
      not H22 from the M1 site which is ascribed as the lower affinity site.

PMID- 11467954
TI  - Identification of a determinant of epidermal growth factor receptor ligand
      binding specificity using a truncated, high-affinity form of the ectodomain.
AB  - Murine and human epidermal growth factor receptors (EGFRs) bind human EGF (hEGF),
      mouse EGF (mEGF), and human transforming growth factor alpha (hTGF-alpha) with
      high affinity despite the significant differences in the amino acid sequences of
      the ligands and the receptors. In contrast, the chicken EGFR can discriminate
      between mEGF (and hEGF) and hTGF-alpha and binds the EGFs with approximately 100
      fold lower affinity. The regions responsible for this poor binding are known to
      be Arg(45) in hEGF and the L2 domain in the chicken EGFR. In this study we have
      produced a truncated form of the hEGFR ectodomain comprising residues 1-501
      (sEGFR501), which, unlike the full-length hEGFR ectodomain (residues 1-621,
      sEGFR621), binds hEGF and hTGF-alpha with high affinity (K(D) = 13-21 and 35-40
      nM, respectively). sEGFR501 was a competitive inhibitor of EGF-stimulated
      mitogenesis, being almost 10-fold more effective than the full-length EGFR
      ectodomain and three times more potent than the neutralizing anti-EGFR monoclonal
      antibody Mab528. Analytical ultracentrifugation showed that the primary EGF
      binding sites on sEGFR501 were saturated at an equimolar ratio of ligand and
      receptor, leading to the formation of a 2:2 EGF:sEGFR501 dimer complex. We have
      used sEGFR501 to generate three mutants with single position substitutions at
      Glu(367), Gly(441), or Glu(472) to Lys, the residue found in the corresponding
      positions in the chicken EGFR. All three mutants bound hTGF-alpha and were
      recognized by Mab528. However, mutant Gly(441)Lys showed markedly reduced binding
      to hEGF, implicating Gly(441), in the L2 domain, as part of the binding site that
      recognizes Arg(45) of hEGF.

PMID- 11467955
TI  - Phox homology domains specifically bind phosphatidylinositol phosphates.
AB  - The recruitment of specific cytosolic proteins to intracellular membranes through
      binding phosphorylated derivatives of phosphatidylinositol (PtdIns) controls such
      processes as endocytosis, regulated exocytosis, cytoskeletal organization, and
      cell signaling. Protein modules such as FVYE domains and PH domains that bind
      specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides,
      respectively, can direct such membrane targeting. Here we show that two
      representative Phox homology (PX) domains selectively bind to specific
      phosphatidylinositol phosphates. The PX domain of Vam7p selectively binds PtdIns
      3-P, while the PX domain of the CPK PI-3 kinase selectively binds PtdIns-4,5
      P(2). In contrast, the PX domain of Vps5p displays no binding to any PtdInsPs
      that were tested. In addition, the double mutant (Y42A/L48Q) of the PX domain of
      Vam7p, reported to cause vacuolar trafficking defects in yeast, has a
      dramatically decreased level of binding to PtdIns-3-P. These data reveal that the
      membrane targeting function of the Vam7p PX domain is based on its ability to
      associate with PtdIns-3-P, analogous to the function of FYVE domains.

PMID- 11467956
TI  - ATR-FTIR study of the structure and orientation of transmembrane domains of the
      Saccharomyces cerevisiae alpha-mating factor receptor in phospholipids.
AB  - The structures of seven synthetic transmembrane domains (TMDs) of the alpha
      factor receptor (Ste2p) from Saccharomyces cerevisiae were studied in
      phospholipid multilayers by transmission Fourier transform infrared (FTIR) and
      attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopies.
      Peptide conformation assumed in multilayers depended on the method of sample
      preparation. Amide proton H/D exchange experiments showed that 60-80% of the NH
      bonds in these TMDs did not exchange with bulk water in 1,2-dimyristoyl-sn
      glycero-3-phosphocholine (DMPC) multilayers. FTIR results showed that peptides
      corresponding to TMDs one, two, and seven were mostly alpha-helical in DMPC
      multilayers. Peptides corresponding to TMDs three and six assumed predominantly
      beta-sheet structures, whereas those corresponding to TMDs four and five were a
      mixture of alpha-helices and beta-sheets. ATR-FTIR showed that in DMPC the alpha
      helices of TMDs two and five oriented with tilt angles of 34 degrees and 32
      degrees, respectively, with respect to the multilayer normal. Similar results
      were obtained for six of the transmembrane domains in DMPC/DMPG (4:1)
      multilayers. In a mixture [POPC/POPE/POPS/PI/ergosterol (30:20:5:20:25)] which
      mimicked the lipid composition of the S. cerevisiae cell membrane, the percentage
      of alpha-helical structures found for TMDs one and five increased compared to
      those in DMPC and DMPC/DMPG (4:1) multilayers, and TMD six exhibited a mixture of
      beta-sheet ( approximately 60%) and alpha-helical ( approximately 40%) structure.
      These experiments provide biophysical evidence that peptides representing the
      seven transmembrane domains in Ste2p assume different structures and tilt angles
      within a membrane multilayer.

PMID- 11467957
TI  - Structural requirements for conserved arginine of parathyroid hormone.
AB  - Arg-20 is one of two residues conserved in all peptides known to activate the
      parathyroid hormone (PTH) receptor. Previous studies have failed to find any
      naturally encoded analogues of residue 20 that had any adenylyl cyclase (AC)
      stimulating activity. In this work we have studied substitutions of Arg-20 with
      nonencoded amino acids and conformationally constrained analogues with side
      chains mimicking that of Arg. No analogue had more than 20% of the AC-stimulating
      ability of the natural Arg-20-bearing peptide. In descending order of activity,
      the most active analogues had (S)-4-piperidyl-(N-amidino)glycine (PipGly),
      norleucine (Nle), citrulline (Cit), or ornithine (Orn) at residue 20. Analogues
      with Arg-20 substituted with L-4-piperidyl-(N-amidino)alanine, Lys, Glu, Ala,
      Gln, (S)-2-amino-4-[(2-amino)pyrimidinyl]butanoic acid, or L-(4
      guanidino)phenylalanine had very low or negligible activity. Low or negligible
      activities of Lys or Orn analogues suggested ionic interactions play a minor role
      in the Arg interaction with the receptor. The conformational constraints imposed
      by the PipGly ring had a negative effect on its ability to substitute for Arg.
      The side-chain H-bonding potential of the Cit ureimido group was likely an
      important factor in its mimicry of Arg. The increase in amphiphilicity, as
      demonstrated by its greater high-performance liquid chromatographic retention,
      and increased alpha-helix, as shown by circular dichroic spectroscopy, likely
      contributed to the activity of the Nle-20 analogue. The data demonstrated that
      specific H-bonding, hydrophobicity of the side chain, stabilization of alpha
      helix, and possibly specific cation positioning were all important in the
      interaction of Arg-20 with receptor groups.

PMID- 11467958
TI  - Kinetic and calorimetric evidence for two distinct scaffolding protein binding
      populations within the bacteriophage P22 procapsid.
AB  - A wide variety of viruses require the transient presence of scaffolding proteins
      to direct capsid assembly. In the case of bacteriophage P22, a model in which the
      scaffolding protein selectively stabilizes on-pathway growing intermediates has
      been proposed. The stoichiometry and thermodynamics of binding of the
      bacteriophage P22 scaffolding protein within the procapsid were analyzed by light
      scattering and isothermal titration calorimetry. Calorimetric experiments carried
      out between 10 and 37 degrees C were consistent with the presence of at least two
      distinct populations of binding sites, in agreement with kinetic evidence
      obtained by a light scattering assay. Binding to the high-affinity sites occurred
      at 20 degrees C with a stoichiometry of approximately 60 scaffolding molecules
      per procapsid and an apparent K(d) of approximately 100-300 nM and was almost
      completely enthalpy-driven. For the second binding population, precise fitting of
      the data was impossible due to small heats of binding, but the thermodynamics of
      binding were clearly distinct from the high-affinity phase. The heat capacity
      change (DeltaC(p)()) of binding was large for the high-affinity sites and
      negative for both sets of sites. Addition of sodium chloride (1 M) greatly
      reduced the magnitude of the apparent DeltaH, in agreement with previous evidence
      that electrostatic interactions play a major role in binding. A mutant
      scaffolding protein that forms covalent dimers (R74C/L177I) bound only to the
      high-affinity sites. These data comprise the first quantitative measurements of
      the energetics of the coat protein/scaffolding protein interaction.

PMID- 11467959
TI  - Kinetic study of folding and misfolding of diacylglycerol kinase in model
      membranes.
AB  - Despite the relevance of membrane protein misfolding to a number of common
      diseases, our understanding of the folding and misfolding of membrane proteins
      lags well behind soluble proteins. Here, the overall kinetics of membrane
      insertion and folding of the homotrimeric integral membrane protein
      diacylglycerol kinase (DAGK) is addressed. DAGK was purified into lipid/detergent
      free urea and guanidinium solutions and subjected to general structural
      characterization. In urea, the enzyme was observed to be monomeric but maintained
      considerable tertiary structure. In guanidinium, it was also monomeric but
      exhibited much less tertiary structure. Aliquots of these DAGK stock solutions
      were diluted 200-fold into lipid vesicles or into detergent/lipid mixed micelles,
      and the rates and efficiencies of folding/insertion were monitored. Reactions
      were also carried out in which micellar DAGK solutions were diluted into
      vesicular solutions. Productive insertion of DAGK from denaturant solutions into
      mixed micelles occurred much more rapidly than into lipid vesicles, suggesting
      that bilayer transversal represents the rate-limiting step for DAGK assembly in
      vesicles. The efficiency of productive folding/insertion into vesicles was
      highest in reactions initiated with micellar DAGK stock solutions (where DAGK
      maintains a nativelike fold and oligomeric state) and lowest in reactions
      starting with guanidinium stocks (where DAGK is an unfolded monomer). Moreover,
      the final ratio of irreversibly misfolded DAGK to reversibly misfolded enzyme was
      highest following reactions initiated with guanidinium stock solutions and lowest
      when micellar stocks were used. Finally, it was also observed that very low
      concentrations of detergents were able to both enhance the bilayer insertion rate
      and suppress misfolding.

PMID- 11467960
TI  - A designed protein with packing between left-handed and right-handed helices.
AB  - A common motif in protein structures is the assembly of alpha-helices. Natural
      alpha-helical assemblies, such as helical bundles and coiled coils, consist of
      multiple right-handed alpha-helices. Here we design a protein complex containing
      both left-handed and right-handed helices, with peptides of D- and L-amino acids,
      respectively. The two peptides, D-Acid and L-Base, feature hydrophobic heptad
      repeats and are designed to pack against each other in a "knobs-into-holes"
      manner. In solution, the peptides form a stable, helical heterotetramer with
      tight packing in the most solvent-protected core. This motif may be useful for
      designing protease-resistant, helical D-peptide ligands against biological
      protein targets.

PMID- 11467961
TI  - Evidence for isoniazid-dependent free radical generation catalyzed by
      Mycobacterium tuberculosis KatG and the isoniazid-resistant mutant KatG(S315T).
AB  - The antitubercular agent isoniazid can be activated by Mycobacterium tuberculosis
      KatG using either a peroxidase compound I/II or a superoxide-dependent oxyferrous
      pathway. The identity of activated isoniazid is unknown, but it has been
      suggested that it may be a free radical intermediate. In this work, EPR spin
      trapping experiments detected isoniazid-derived radicals generated during KatG
      mediated oxidation via the peroxidase compound I/II pathway. On the basis of
      hyperfine splitting patterns and oxygen dependence, these radicals were
      identified as the acyl, acyl peroxo, and pyridyl radicals of isoniazid. Isoniazid
      resistant KatG(S315T) produced the same radicals found with KatG, while the less
      potent antitubercular agent nicotinic acid hydrazide produced the corresponding
      nicotinyl radicals. The time course of radical production was similar for KatG
      and KatG(S315T), while a lower steady-state level of radicals was produced from
      nicotinic acid hydrazide. These results support an earlier finding that the
      peroxidase pathway does not correlate with isoniazid resistance conferred by
      KatG(S315T). Trace amounts of radicals were detected via the superoxide-dependent
      pathway. The low level of isoniazid-derived radicals found in the superoxide
      dependent pathway may be due to scavenging by superoxide.

PMID- 11467962
TI  - Low-temperature Fourier transform infrared spectroscopy of photoactive yellow
      protein.
AB  - The photocycle intermediates of photoactive yellow protein (PYP) were
      characterized by low-temperature Fourier transform infrared spectroscopy. The
      difference FTIR spectra of PYP(B), PYP(H), PYP(L), and PYP(M) minus PYP were
      measured under the irradiation condition determined by UV-visible spectroscopy.
      Although the chromophore bands of PYP(B) were weak, intense sharp bands
      complementary to the 1163-cm(-1) band of PYP, which show the chromophore is
      deprotonated, were observed at 1168-1169 cm(-1) for PYP(H) and PYP(L), indicating
      that the proton at Glu46 is not transferred before formation of PYP(M). Free
      trans-p-coumaric acid had a 1294-cm(-1) band, which was shifted to 1288 cm(-1) in
      the cis form. All the difference FTIR spectra obtained had the pair of bands
      corresponding to them, indicating that all the intermediates have the chromophore
      in the cis configuration. The characteristic vibrational modes at 1020-960 cm(-1)
      distinguished the intermediates. Because these modes were shifted by deuterium
      labeling at the ethylene bond of the chromophore while labeling at the phenol
      part had no effect, they were attributed to the ethylene bond region. Hence,
      structural differences among the intermediates are present in this region. Bands
      at about 1730 cm(-1), which show that Glu46 is protonated, were observed for all
      intermediates except for PYP(M). Because the frequency of this mode was constant
      in PYP(B), PYP(H), and PYP(L), the environment of Glu46 is conserved in these
      intermediates. The photocycle of PYP would therefore proceed by changing the
      structure of the twisted ethylene bond of the chromophore.

PMID- 11467963
TI  - A novel role of XRCC1 in the functions of a DNA polymerase beta variant.
AB  - In the base excision repair pathway, wild-type DNA polymerase beta (WT polbeta)
      provides most of the gap filling synthesis. A truncated polbeta protein
      (polbetaDelta), expressed in primary colorectal and breast tumors and in a
      primary culture of renal cell carcinoma, inhibits the gap filling synthesis and
      DNA binding activities of WT polbeta. However, a purified recombinant
      polbetaDelta does not inhibit a purified WT polbeta. To determine the dominant
      inhibitory activity of polbetaDelta, we examined interactions of purified
      polbetaDelta with X-ray cross complementing group 1 (XRCC1), poly(ADP-ribose)
      polymerase (PARP), and apurinic endonuclease (Ape) proteins. All of these
      proteins interact with polbetaDelta in vitro and in vivo. The polbetaDelta
      protein can fill one nucleotide gap by inserting a base at the AP site, whereas a
      presumed binary complex of polbetaDelta and XRCC1 cannot. However, this binary
      complex not only suppresses gap filling synthesis activity of WT polbeta but also
      binds more strongly to gapped DNA than WT polbeta bound to XRCC1. These results
      are the first to suggest that XRCC1 is directly involved in the dominant negative
      activity of truncated polbeta, possibly leading to the genomic instability
      characteristic of tumor cells.

PMID- 11467964
TI  - DNA polymerase beta: pre-steady-state kinetic analyses of dATP alpha S
      stereoselectivity and alteration of the stereoselectivity by various metal ions
      and by site-directed mutagenesis.
AB  - The first pre-steady-state kinetic analysis of the stereoselectivity of a DNA
      polymerase, Pol beta from rat brain, toward Rp and Sp isomers of dATPalphaS, and
      alteration of the stereoselectivity by various metal ions and by site-directed
      mutagenesis are reported. Diastereomers of dATPalphaS were synthesized by
      enzymatic methods to >98% purity. The rate of polymerization (k(pol)) and the
      apparent dissociation constant (K(d,app)) were measured with dATP, Rp-dATPalphaS,
      and Sp-dATPalphaS in the presence of Mg(2+), Mn(2+), or Cd(2+). The results
      indicate that wild type (WT) polymerase (Pol) beta can incorporate both Sp- and
      Rp-dATPalphaS in the presence of Mg(2+), but Sp is the preferred isomer. The
      stereoselectivity, defined as (k(pol)/K(d))(Sp)/(k(pol)/K(d))(Rp) (abbreviated
      Sp/Rp ratio), is 57.5 in the presence of Mg(2+). When Mg(2+) was substituted with
      Mn(2+) and Cd(2+), the Sp/Rp ratio decreased to 7.6 and 21, respectively. These
      results are discussed in relation to the crystal structures of various Pol beta
      complexes, as well as previous steady-state kinetic studies of other DNA
      polymerases. In addition, the D276R mutant was designed to introduce a potential
      extra hydrogen bonding interaction between the arginine side chain and the pro-Sp
      oxygen of the alpha-phosphate of dNTP. The kinetic data of the D276R mutant
      showed a pronounced relaxation of stereoselectivity of dATPalphaS (Sp/Rp ratio =
      1.5, 3.7, and 1.5 for Mg(2+), Mn(2+), and Cd(2+), respectively). Furthermore, the
      D276R mutant showed a 5-fold enhanced reactivity toward Rp-dATPalphaS relative to
      WT Pol beta, suggesting that this mutant Pol beta can be used to incorporate Rp
      dNTPalphaS into DNA oligomers.

PMID- 11467965
TI  - In vitro reconstitution of the Pseudomonas aeruginosa nonribosomal peptide
      synthesis of pyochelin: characterization of backbone tailoring thiazoline
      reductase and N-methyltransferase activities.
AB  - During iron starvation the Gram-negative pathogenic bacterium Pseudomonas
      aeruginosa makes the nonribosomal peptide siderophore pyochelin by a four
      protein, 11 domain assembly line, involving a cascade of acyl-S-enzyme
      intermediates on the PchE and PchF subunits that are elongated, heterocyclized,
      reduced, and N-methylated before release. Purified PchG is shown to be an NADPH
      dependent reductase for the hydroxyphenylbisthiazoline-S-PchF acyl enzyme,
      regiospecifically converting one of the dihydroheterocyclic thiazoline rings to a
      thiazolidine. The K(m) for the PchG protein is 1 microM, and the k(cat) for
      throughput to pyochelin is 2 min(-1). The nitrogen of the newly generated
      thiazolidine ring can be N-methylated upon addition of SAM, to yield the mature
      pyochelin chain still tethered as a pyochelinyl-S-PchF at the PCP domain. A
      presumed methyltransferase (MT) domain embedded in the PchF subunit catalyzes
      this N-methylation. Mutation of a conserved G to R in the MT core motif abolishes
      MT activity and subsequent chain release from PchF. The thioesterase (TE) domain
      of PchF catalyzes hydrolytic release of the fully mature pyochelinyl chain to
      produce the pyochelin siderophore at a rate of 2 min(-1), at least 30-40-fold
      faster than in the absence of hydroxyphenylbisthiazolinyl-COOH (HPTT-COOH) chain
      reduction and N-methylation. A mutation in the PchF TE domain does not catalyze
      autodeacylation and release of the pyochelinyl-S-enzyme. Thus, full
      reconstitution of the nonribosomal peptide synthetase assembly line by purified
      protein components has been obtained for production of this tandem
      bisheterocyclic siderophore.

PMID- 11467966
TI  - Crystal structures of amylosucrase from Neisseria polysaccharea in complex with D
      glucose and the active site mutant Glu328Gln in complex with the natural
      substrate sucrose.
AB  - The structure of amylosucrase from Neisseria polysaccharea in complex with beta-D
      glucose has been determined by X-ray crystallography at a resolution of 1.66 A.
      Additionally, the structure of the inactive active site mutant Glu328Gln in
      complex with sucrose has been determined to a resolution of 2.0 A. The D-glucose
      complex shows two well-defined D-glucose molecules, one that binds very strongly
      in the bottom of a pocket that contains the proposed catalytic residues (at the
      subsite -1), in a nonstrained (4)C(1) conformation, and one that binds in the
      packing interface to a symmetry-related molecule. A third weaker D-glucose
      binding site is located at the surface near the active site pocket entrance. The
      orientation of the D-glucose in the active site emphasizes the Glu328 role as the
      general acid/base. The binary sucrose complex shows one molecule bound in the
      active site, where the glucosyl moiety is located at the alpha-amylase -1
      position and the fructosyl ring occupies subsite +1. Sucrose effectively blocks
      the only visible access channel to the active site. From analysis of the complex
      it appears that sucrose binding is primarily obtained through enzyme interactions
      with the glucosyl ring and that an important part of the enzyme function is a
      precise alignment of a lone pair of the linking O1 oxygen for hydrogen bond
      interaction with Glu328. The sucrose specificity appears to be determined
      primarily by residues Asp144, Asp394, Arg446, and Arg509. Both Asp394 and Arg446
      are located in an insert connecting beta-strand 7 and alpha-helix 7 that is much
      longer in amylosucrase compared to other enzymes from the alpha-amylase family
      (family 13 of the glycoside hydrolases).

PMID- 11467967
TI  - Regulation of the plant-type 5'-adenylyl sulfate reductase by oxidative stress.
AB  - 5'-Adenylyl sulfate (APS) reductase (EC 1.8.4.9) catalyzes a key reaction in the
      plant sulfate assimilation pathway leading to the synthesis of cysteine and the
      antioxidant glutathione. In Arabidopsis thaliana APS reductase is encoded by a
      family of three genes. In vitro biochemical studies revealed that the enzyme
      product derived from one of them (APR1) is activated by oxidation, probably
      through the formation of a disulfide bond. The APR1 enzyme is 45-fold more active
      when expressed in a trxB strain of Escherichia coli than in a trxB(+) wild type.
      The enzyme is inactivated in vitro by treatment with disulfide reductants and is
      reactivated with thiol oxidants. Redox titrations show that the regulation site
      has a midpoint potential of -330 mV at pH 8.5 and involves a two-electron redox
      reaction. Exposure of a variety of plants to ozone induces a rapid increase in
      APS reductase activity that correlates with the oxidation of the glutathione pool
      and is followed by an increase in free cysteine and total glutathione. During the
      response to ozone, the level of immunodetectable APS reductase enzyme does not
      increase. Treatment of A. thaliana seedlings with oxidized glutathione or
      paraquat induces APS reductase activity even when transcription or translation is
      blocked with inhibitors. The results suggest that a posttranslational mechanism
      controls APS reductase. A model is proposed whereby redox regulation of APS
      reductase provides a rapidly responding, self-regulating mechanism to control the
      glutathione synthesis necessary to combat oxidative stress.

PMID- 11467968
TI  - Temperature-induced denaturation and renaturation of triosephosphate isomerase
      from Saccharomyces cerevisiae: evidence of dimerization coupled to refolding of
      the thermally unfolded protein.
AB  - The thermal denaturation of the dimeric enzyme triosephosphate isomerase (TIM)
      from Saccharomyces cerevisiae was studied by spectroscopic and calorimetric
      methods. At low protein concentration the structural transition proved to be
      reversible in thermal scannings conducted at a rate greater than 1.0 degrees C
      min(-1). Under these conditions, however, the denaturation-renaturation cycle
      exhibited marked hysteresis. The use of lower scanning rates lead to pronounced
      irreversibility. Kinetic studies indicated that denaturation of the enzyme likely
      consists of an initial first-order reaction that forms thermally unfolded (U)
      TIM, followed by irreversibility-inducing reactions which are probably linked to
      aggregation of the unfolded protein. As judged from CD measurements, U possesses
      residual secondary structure but lacks most of the tertiary interactions present
      in native TIM. Furthermore, the large increment in heat capacity upon
      denaturation suggests that extensive exposure of surface area occurs when U is
      formed. Above 63 degrees C, reactions leading to irreversibility were much slower
      than the unfolding process; as a result, U was sufficiently long-lived as to
      allow an investigation of its refolding kinetics. We found that U transforms into
      nativelike TIM through a second-order reaction in which association is coupled to
      the regain of secondary structure. The rate constants for unfolding and refolding
      of TIM displayed temperature dependences resembling those reported for monomeric
      proteins but with considerably larger activation enthalpies. Such large
      temperature dependences seem to be determinant for the occurrence of kinetically
      controlled transitions and thus constitute a simple explanation for the
      hysteresis observed in thermal scannings.

PMID- 11467969
TI  - Genetic conflict, genomic imprinting and establishment of the epigenotype in
      relation to growth.
AB  - Genomic imprinting is the process that differentially modifies the parental
      alleles at certain genetic loci in the parental germlines. Such modifications of
      DNA and chromatin are somatically heritable and cause unequal expression of the
      parental alleles during subsequent development. In mammals, imprinted genes
      encode a relatively small number of functionally heterogeneous proteins.
      Nevertheless, imprinted genes exert important effects, primarily on fetal
      development, and their deregulation is implicated in a variety of pathologies
      including sporadic, inherited and induced growth disorders. Imprinted loci show
      several unusual structural and functional characteristics that may be related to
      mechanistic aspects of mono-allelic expression or to modes of evolution of
      imprinted genetic loci. Typically, imprinted genes are clustered in certain
      genomic regions and have relatively reduced intronic DNA content relative to non
      imprinted genes. In addition, their regulatory regions frequently contain a
      combination of features including tandem repeats associated with differentially
      methylated CpG islands and overlapping transcription of coding or non-coding
      RNAs. The evolution of imprinting can be understood as the stable outcome of
      sexual selection acting differently on the parental alleles of genes that
      influence parental investment in offspring. Consistent with this explanation,
      imprinted genes are expressed predominantly during embryonic and postnatal
      development in mammals and in the developing endosperm of plants, and maternal or
      paternal expression at imprinted loci is associated with reduced or increased
      parental investment, respectively. Such selective forces have implications for
      understanding mechanistic aspects of genome reprogramming in the early mammalian
      embryo.

PMID- 11467970
TI  - Fetal growth restriction: adaptations and consequences.
AB  - A range of pathophysiological factors can result in a perturbation or restriction
      of fetal growth, and the cardiovascular, neuroendocrine and metabolic adaptations
      of the fetus to these stimuli will depend on their nature, timing and intensity.
      The critical importance of these physiological adaptations for both immediate
      survival and long-term health outcomes has provided an impetus for experimental
      studies of the nature and consequences of specific fetal adaptations to a poor
      intrauterine environment. This review summarizes data from recent studies that
      have focused on the responses of the fetal cardiovascular, sympathoadrenal,
      hypothalamo-pituitary-adrenal and renin-angiotensin systems to experimental
      restriction of placental function in the sheep and discusses the consequences of
      these adaptations for fetal, neonatal and adult health.

PMID- 11467971
TI  - Effects of nutrition and environmental factors on the fetal programming of the
      reproductive axis.
AB  - Research from a wide range of scientific disciplines has shown that the
      reproductive performance of animals in adult life is determined, in part, by a
      variety of extraneous influences acting at different stages of development from
      before conception until after birth. These effects are probably mediated through
      changes in the hypothalamic-pituitary and gonadal axes but the physiological
      system that is affected depends on the stage of development at which the
      influence is applied. The physiological mechanisms through which environmental
      influences are transmitted to the target organs are, in many cases, complex and
      poorly understood. Gonadotrophins seem to play a pivotal role in the development
      of the fetal testis, although effects of environmental influences on GnRH
      secretion have yet to be demonstrated. Other studies have shown that, at earlier
      stages of fetal development, the normal ontogeny of gonadal development and
      function can be disrupted by undernutrition or the influence of endocrine
      disrupting compounds. Specifically, in female fetuses, the onset of meiosis is
      delayed, whereas, in male fetuses, testosterone synthesis is increased as a
      result of enhanced testicular steroidogenic enzyme activity. Although
      reproductive performance is clearly influenced by prenatal factors, much further
      work is required to identify the relationships between developmental
      abnormalities and adult reproductive function. Work is also required to elucidate
      further the critical windows in development and the mechanisms by which
      environmental factors affect the reproductive organs of developing offspring.

PMID- 11467972
TI  - Intraovarian actions of oestrogen.
AB  - Oestrogen regulates several hypothalamic and pituitary hormones, which in turn
      control ovarian functions. Oestrogen and its metabolites, such as
      catecholoestrogens, also have direct effects within the ovary. This review
      examines the roles of oestrogen in regulating ovarian folliculogenesis, ovulation
      and corpus luteum formation. Oestrogen promotes follicular development, which
      culminates in ovulation, by potentiating follicular development, granulosa cell
      expression of gonadotrophin receptors, steroidogenesis, and gap junction
      formation by granulosa cells, and by inhibiting granulosa cell apoptosis. In
      addition, oestrogen may be needed for corpus luteum formation and maintenance.
      Studies on mutant mice that either lack one or both of the known oestrogen
      receptors or are unable to synthesize oestrogen support some but not all of these
      prior inferences of the roles of oestrogen within the ovary. Although these
      transgenic mice have proved useful in determining some of the intraovarian
      actions of oestrogen, they present confounding problems, including hormonal
      imbalances, that hinder interpretation. Transgenic mice with conditional or
      tissue-directed mutations in their oestrogen receptors are needed to dissect the
      ovarian actions of oestrogen further. In addition, microarray technologies,
      combined with specific hormone treatment regimens are likely to provide an
      attractive, alternative approach to using mutant mice in clarifying the direct
      actions of oestrogen in the ovaries of other species.

PMID- 11467973
TI  - Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during
      fetal and postnatal development in mice.
AB  - The role of the gonadotrophins in regulating numbers of Leydig and Sertoli cells
      during fetal and postnatal development was examined using normal mice and
      hypogonadal (hpg) mice, which lack circulating gonadotrophins. The disector
      method was used to determine the number of cells from day 16 of gestation until
      adulthood. The numbers of Leydig cells did not change significantly between day
      16 of gestation and day 5 after parturition in normal mice and were not
      significantly different from numbers in hpg mice at any age up to day 5 after
      parturition. There was a 16-fold increase in the number of Leydig cells in normal
      mice between day 5 and day 20 after parturition, followed by a further doubling
      of number of cells between day 20 and adulthood. The number of Leydig cells in
      hpg testes did not change between day 5 and day 20 after parturition but doubled
      between day 20 and adulthood so that the number of cells was about 10% of normal
      values from day 20 onwards. Leydig cell volume was constant in normal animals
      from birth up to day 20 and then showed a 2.5-fold increase in adult animals.
      Leydig cell volume was normal in hpg testes at birth but decreased thereafter and
      was about 20% of normal volume in adult mice. The number of Sertoli cells
      increased continuously from day 16 of gestation to day 20 after gestation in
      normal mice and then remained static until adulthood. The number of Sertoli cells
      in hpg testes was normal throughout fetal life but was reduced by about 30% on
      day 1 (day of parturition). Thereafter, Sertoli cells proliferated at a slower
      rate but over a longer period in the hpg testis so that on day 20 after
      parturition the number of Sertoli cells was about 50% of normal values, whereas
      in adult mice the number was 65% of normal. The number of gonocytes did not
      change between day 16 of gestation and day 1 and did not differ between normal
      and hpg testes. The number of gonocytes increased nine-fold in normal testes but
      only three-fold in hpg testes between day 1 and day 5 after parturition.
      Gonocytes differentiated into spermatogonia in both normal and hpg testes between
      day 5 and day 20 after parturition. These results show: (i) that fetal
      development of both Sertoli and Leydig cells is independent of gonadotrophins;
      (ii) that normal differentiation and proliferation of the adult Leydig cell
      population (starting about day 10 after parturition) is dependent on the presence
      of gonadotrophins; and (iii) that the number of Sertoli cells after birth is
      regulated by gonadotrophins, although proliferation will continue, at a lower
      rate and for longer, in the absence of gonadotrophins.

PMID- 11467974
TI  - Regulation of the strypsin-related proteinase ISP2 by progesterone in endometrial
      gland epithelium during implantation in mice.
AB  - Hormones prepare the uterus for the arrival and subsequent invasion of the embryo
      during pregnancy. Extracellular matrix-degrading proteinases and their inhibitors
      are involved in this integration process. Recent genetic evidence indicates that
      there is redundancy within the implantation proteinase cascade, indicating that
      additional proteinases may be involved. Recently, we described a novel
      implantation serine proteinase (ISP1) gene that encodes the embryo-derived enzyme
      strypsin, which is necessary for blastocyst hatching in vitro and the initiation
      of invasion. The evidence presented in the present study indicates that a second
      proteinase secreted from the uterus also participates in lysis of the zona
      pellucida. A second implantation serine proteinase gene (ISP2) was isolated,
      which encodes a related secreted tryptase expressed specifically within uterine
      endometrial glands. In pseudopregnancy, ISP2 gene expression is dependent on
      progesterone priming and is inhibited by the antiprogestin RU486. On the basis of
      similarities between ISP2 gene expression and that of a progesterone-regulated
      luminal proteinase associated with lysis of the zona pellucida, it is possible
      that the strypsin-related protein, ISP2, may encode a zona lysin proteinase.

PMID- 11467975
TI  - Differential effects of prostaglandin F2alpha on in vitro luteinized bovine
      granulosa cells.
AB  - Prostaglandins have been implicated in various aspects of ovarian function
      including ovulation and luteolysis. In this study, the expression and regulation
      of inducible prostagland in G/H synthase (PGHS-2) and PGF(2alpha) receptors were
      investigated in bovine granulosa cells at various stages of differentiation.
      Firstly, the induction of PGF(2alpha) receptor mRNA and PGHS-2 mRNA in
      preovulatory granulosa cells was evaluated. Granulosa cells were collected from
      preovulatory follicles and cultured for 1, 4, 7 or 10 days. Cells were treated
      with hCG (10 iu) or with increasing doses of forskolin (0-10 micromol l(-1)) for
      24 h. Forskolin increased steady-state concentrations of mRNA for PGHS-2 (> 20
      fold) and PGF(2alpha) receptor (> 1000-fold) in a dose-dependent fashion. Use of
      selective protein kinase A inhibitor (H89) reduced both hCG- and forskolin
      induced expression of PGF(2alpha) receptor mRNA and PGHS-2 mRNA. The hypothesis
      that luteinized granulosa cells would acquire PGF(2alpha) responsiveness similar
      to responses to PGF(2alpha) observed in vivo was also evaluated. Treatment with
      PGF(2alpha) (100 nmol l(-1)) reduced forskolin-induced expression of PGF(2alpha)
      receptor mRNA on days 4, 7 and 10, but not on day 1 of culture (n = 3). Treatment
      with PGF(2alpha) did not change forskolin-induced expression of PGHS-2 mRNA on or
      before day 4 of culture. In contrast, PGF(2alpha) significantly increased PGHS-2
      mRNA expression in granulosa cells primed with forskolin for 7 or 10 days. In
      conclusion, expression of PGHS-2 and PGF(2alpha) receptor mRNA is protein kinase
      A-dependent in preovulatory bovine granulosa cells. Granulosa cells become
      PGF(2alpha)-responsive soon after expression of PGF(2alpha) receptor, whereas
      further differentiation is required before PGF(2alpha) induces PGHS-2 mRNA
      upregulation. These results demonstrate that at least two key transitions are
      required in PGF(2alpha)-induced luteal regression in the mid-cycle corpus luteum.

PMID- 11467976
TI  - Reduction of long-term effects of local heating of the testis by treatment of
      rats with a GnRH agonist and an anti-androgen.
AB  - Heating the testes of anaesthetized adult rats to 43 degrees C for 30 min in a
      waterbath was followed by a large decrease in testis and epididymis mass and
      number of spermatozoa 35 days later. These parameters had recovered to some
      extent, but not completely, by days 70 and 97 after heating, but had decreased
      again in rats examined on day 182. There were no consistent effects of heating on
      androgen status, as determined by the concentrations of testosterone in blood and
      testis fluids, or by seminal vesicle mass, and interstitial fluid volume was
      increased in the heated testes. Treatment of rats with an implant of a GnRH
      agonist and daily injections of an anti-androgen for 14 days (sufficient in
      itself to cause large temporary decreases in tissue mass, number of spermatozoa
      and androgen status) did not reduce the initial decrease in testis mass or number
      of spermatozoa seen after heating, but reduced the later decreases in mass and
      number of spermatozoa significantly. These findings indicate that, as well as
      causing damage to spermatocytes and spermatids, as previously reported, heating
      also reduces the ability of spermatogonia to repopulate the seminiferous tubules
      at longer intervals after heating. Furthermore, it appears that this effect on
      the spermatogonia can be reduced by treating the animals with a GnRH agonist and
      anti-androgen, a treatment similar to that shown by other authors to improve
      recovery of the testis from irradiation or drug treatment.

PMID- 11467977
TI  - Use of computer-assisted sperm motility assessment and multivariate pattern
      analysis to characterize ejaculate quality in Mohor gazelles (Gazella dama
      mhorr): effects of body weight, electroejaculation technique and short-term semen
      storage.
AB  - Subjective and objective semen assessments were performed on 18 male Mohor
      gazelles (Gazella dama mhorr). Sperm motility assessments combined with sperm
      plasma membrane and acrosomal integrity evaluations were undertaken as part of a
      captive breeding programme. The primary objective was to test methodology for
      short-term preservation of gazelle semen for artificial insemination (storage in
      N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulphonic acid-Tris diluent (TEST) for
      up to 96 h at 17 degrees C). However, the secondary objective was to investigate
      phenotypic and genotypic influences on semen quality within this small
      population, which was established in 1971 with only 12 genetic founders. Sperm
      motility was measured by computer-assisted semen assessment and the data were
      analysed using a pattern analysis technique to detect and quantify naturally
      occurring sperm subpopulations within the semen samples. Four sperm
      subpopulations distinguishable by their motion characteristics were detected. The
      relative frequencies of two subpopulations (population 2: highly motile, non
      linear; and population 4: poorly motile, non-linear) in fresh semen were
      correlated with the maximum voltage used during electroejaculation. The frequency
      of subpopulation 2 was negatively correlated with maximum voltage (r = -0.875, P
      < 0.0001) and the frequency of subpopulation 4 was positively correlated (r =
      0.727, P < 0.005). The frequencies of all subpopulations varied significantly
      among the animals sampled (chi-squared = 2577.6, degrees of freedom = 54, P <
      0.0001) and subpopulation 4 was also correlated with body weight (r = -0.59, P <
      0.005). Semen stored at 17 degrees C retained motility, plasma membrane and
      acrosomal integrity for 48 h, but these measures decreased thereafter. The
      frequency of a sperm subpopulation showing uncoordinated but active motility
      increased significantly over the first 48 h and then decreased.

PMID- 11467978
TI  - Immunohistochemical study of the distribution of adrenergic and peptidergic
      innervation in the equine uterus and the cervix.
AB  - Little is known about neurogenic regulation of uterine contractility in mares.
      The present study investigated the distribution of adrenergic and peptidergic
      nerves in the mare uterus. Samples from the uterine horn, body and cervix were
      collected from 18 cyclic mares for immunohistochemistry. The uterus was well
      supplied with adrenergic nerves. A large number of tyrosine hydroxylase- and
      dopamine beta-hydroxylase-immunoreactive nerve bundles and fibres were present in
      the myometrium and endometrium in all regions of the uterus and cervix. These
      adrenergic nerve bundles and fibres travelled parallel to the muscle layers and
      were often associated with blood vessels. The density of peptidergic nerves was
      less than that of adrenergic nerves, but the pattern of distribution was similar.
      Neuropeptide Y-immunoreactive nerve fibres were the most abundant, whereas
      vasoactive intestinal polypeptide- and calcitonin gene-related peptide
      immunoreactive nerve fibres were less frequently seen. Substance P-immunoreactive
      nerve fibres were the most sparse. Peptidergic nerves were distributed among the
      smooth muscle layers and near endometrial glands and were often associated with
      blood vessels in all regions of the uterus. The density of peptidergic nerve
      fibres was similar in the uterine horn and body but was slightly denser in the
      cervix. These findings indicate that uterine innervation may have an important
      role in controlling reproductive functions in mares.

PMID- 11467979
TI  - Dose-response effects of equine chorionic gonadotrophin (eCG) and human chorionic
      gonadotrophin (hCG) on early embryonic development and viable pregnancy rate in
      rats.
AB  - The present study examined the dose-response effects of eCG treatment alone and
      in combination with various doses of hCG on early embryonic development in vivo
      and viable pregnancy rate in rats. Mated female Wistar rats were treated with eCG
      alone (0, 10, 20 or 40 iu), or with 20 iu eCG in combination with various doses
      of hCG (10, 20, 40 or 80 iu) administered 48 h later. The animals were killed on
      days 2, 3, 4, 5 or 14 of pregnancy and the numbers of embryos and fetuses
      recovered were scored. All rats treated with 0 or 10 iu eCG were pregnant. The
      pregnancy rate was reduced from 62.5% on day 2 to 25% on day 14 and from 31% on
      day 2 to 10% on day 14 in the groups treated with 20 and 40 iu eCG, respectively.
      The reduction in pregnancy rate induced by 20 iu eCG was negated by the
      increasing doses of hCG used. A 100% pregnancy rate was noted on days 2 and 3 in
      the groups treated with doses of hCG between 10 and 80 iu and from day 2 to day 4
      in the groups treated with doses of hCG between 20 and 80 iu. However, a higher
      viable pregnancy rate was observed only in the group treated with 10 iu hCG
      compared with the group treated with 20 iu eCG and 0 iu hCG. These results imply
      that hyperstimulation of rats with high doses of eCG compromises pregnancy rate
      and markedly reduces litter size and that the addition of hCG is required for
      complete ovulation, which results in higher embryo yield and a delay in early
      embryo demise.

PMID- 11467980
TI  - Successful non-surgical deep intrauterine insemination with small numbers of
      spermatozoa in sows.
AB  - A 100-fold reduction of the standard dose for artificial insemination in pigs (3
      x 10(9) spermatozoa in 80-100 ml fluid) can be used when spermatozoa are
      deposited surgically next to the uterotubal junction. The present study was
      performed to develop a technique for non-surgical deep intrauterine insemination
      in pigs without sedation of the animal. In Expt 1, sows were weaned, treated to
      induce oestrus and used to evaluate the difficulties involved in the insertion of
      a flexible fibre optic endoscope through the cervix and along the uterine horn.
      Deep uterine catheterizations were performed on each sow at 30-40 h after hCG
      treatment in the crate in which the animal was housed. The endoscope was inserted
      through an artificial insemination spirette, moved through the cervical canal and
      propelled forward along one uterine horn until the entire endoscope was inserted.
      In 30 sows (90.9%) no or minor difficulties were observed during insertion and in
      these animals the procedure was completed in 4.1 +/- 0.26 min. Insertion of the
      endoscope through the cervical canal was not possible in only one sow (3.03%). In
      Expt 2, endoscopic deep intrauterine insemination at 36 h after hCG treatment was
      performed in 15, 18 and 13 sows with 100, 20 or 5 x 10(7) spermatozoa,
      respectively, resulting in farrowing rates of 86.6%, 88.9% and 92.3%,
      respectively; there were no significant differences among groups. Farrowing rates
      after deep intrauterine inseminations were also not different from those achieved
      after standard intracervical insemination with 3 x 10(9) spermatozoa (control
      group: n = 48; 87.5%). Mean litter size (9.41 +/- 0.38 to 10.02 +/- 0.25) was
      also similar among the different experimental and control groups. In conclusion,
      endoscopic non-surgical deep intrauterine inseminations can be performed quickly
      in sows, and normal farrowing rates and litter sizes can be obtained after
      insemination with a small number of spermatozoa.

PMID- 11467981
TI  - Mechanisms of reproductive suppression in female pine voles (Microtus pinetorum).
AB  - In co-operatively breeding birds and mammals, philopatric females are often
      reproductively suppressed. Many studies have focused on the functional
      significance of reproductive suppression, but further investigation of the
      mechanisms involved is required for a complete understanding of this process.
      This study investigated whether reproductive suppression in non-reproductive
      female pine voles (Microtus pinetorum) occurs as a result of lack of gamete
      maturation or lack of increase in LH. The behaviour of male pine voles was also
      examined to determine whether they show a preference for the mother versus her
      daughter, as lack of male stimulation may inhibit an increase of LH in daughter
      pine voles. Ovarian development and circulating LH concentrations were
      investigated in females housed with a prospective mate in the presence or absence
      of a parent. Maturation of gametes was not affected by the presence of a parent.
      In the presence of the mother, there was no increase in LH, as was observed in
      females housed with or exposed to a novel male. Males spent more time with
      mothers and possibly showed a preference for mating with the mother. These
      results are consistent with the contention that ovulation does not occur in
      female pine voles housed in the presence of their mother; however, it is not
      clear whether the lack of ovulation is caused by lack of stimulation from the
      male or suppression by the mother.

PMID- 11467982
TI  - Carbohydrate mediation of boar sperm binding to oviductal epithelial cells in
      vitro.
AB  - After mating, mammalian spermatozoa are transported to the lower oviductal
      isthmus. Spermatozoa are sequestered at the isthmus by attaching and interacting
      with oviductal epithelial cells, hence forming a sperm reservoir. In several
      mammalian species, specific carbohydrates mediate sperm-oviductal epithelial cell
      binding. A quantitative in vitro free cell bioassay was developed to investigate
      the involvement of carbohydrate recognition in pig sperm-oviductal epithelial
      cell interactions. This assay was validated. The sensitivity of the assay was
      such that it was possible to discriminate between different sperm concentrations
      and sperm-oviductal epithelial cell co-incubation periods, spermatozoa with
      damaged plasma membranes and epithelial cells of non-reproductive origin. Optimal
      conditions were used to incubate spermatozoa and oviductal epithelial cells in
      the presence of six hexose sugars at concentrations of 0, 2, 10 and 50 mmol l(
      1). A significant (P < or = 0.05) reduction in the binding of spermatozoa to the
      oviductal epithelium was detected with 2, 10 and 50 mmol maltose l(-1), 50 mmol
      lactose l(-1) and 50 mmol mannose l(-1). These findings support the hypothesis
      that attachment of pig spermatozoa to oviductal epithelium before fertilization
      is mediated by carbohydrate recognition.

PMID- 11467983
TI  - Function and localization of oxytocin receptors in the reproductive tissue of
      rams.
AB  - Oxytocin is present in the male reproductive tract and has been shown to increase
      contractility in the epididymis and to modulate steroidogenesis. This study
      investigated the effects of oxytocin in the testis in vivo, and the presence and
      cellular localization of oxytocin receptors in the reproductive tract of rams.
      During the breeding season, mature rams underwent efferent duct ligation before
      injection of either oxytocin (20 microg) or oxytocin plus an oxytocin antagonist
      (20 microg) into the testicular artery; the contralateral testicular artery
      received saline. Injection of oxytocin caused a significant increase (P < 0.05)
      in the concentration of spermatozoa collected from the rete testis. This effect
      was not observed after treatment with the oxytocin antagonist plus oxytocin.
      Western blot analysis performed using a specific oxytocin receptor antibody (020)
      identified a single immunoreactive band of 66 kDa in testicular and epididymal
      tissue. This band was present in uterine tissue but not in liver or muscle.
      Immunocytochemistry identified oxytocin receptors on Leydig and Sertoli cells of
      the testis, on epithelial cells throughout the epididymis, on peritubular smooth
      muscle cells in the cauda epididymidis, and on the epithelial cells and circular
      smooth muscle layer of the ductus deferens. These findings indicate that oxytocin
      can modulate sperm transport in the ram testis. A role for oxytocin in promoting
      sperm transit is supported by the localization of oxytocin receptors in the cauda
      epididymis and ductus deferens, and the presence of receptors on Leydig, Sertoli
      and epididymal epithelial cells provides further evidence that oxytocin may be
      involved in the local regulation of steroidogenesis.

PMID- 11467984
TI  - Role of quinine-sensitive ion channels in volume regulation in boar and bull
      spermatozoa.
AB  - The ability to reverse swelling caused by hypo-osmotic stress is an important
      cell function; in spermatozoa, it is likely to be of consequence during
      ejaculation and also during the thawing process that terminates cryopreservation.
      In this study, the time course of boar and bull sperm volume changes after
      exposure to hypo-osmotic conditions at 39 degrees C was recorded. Cell volume
      measurements of washed sperm suspensions were performed electronically in Hepes
      buffered saline solutions of 300 and 180 mosmol kg(-1) containing 2.5 mmol K(+)
      l(-1). Treatment with quinine in the presence or absence of the potassium
      ionophore valinomycin was used to determine whether potassium channels were
      involved in the reversal of swelling. After exposure to hypo-osmotic conditions,
      both bull and boar spermatozoa showed initial swelling (up to 200% and 140% of
      initial volume, respectively, within 5 min), which was subsequently partially
      reversed (to about 150% and 120%, respectively, after 20 min). Incubation with
      quinine led to an increase in swelling in both species. However, bull sperm
      volume was already maximal (up to 294%) after 30 s and declined thereafter,
      whereas boar sperm volume increased slowly to a maximum of about 220% after 20
      min. Valinomycin treatment caused quinine-induced swelling in bull spermatozoa to
      decrease rapidly to control (no quinine, no valinomycin) values, whereas in
      quinine-treated boar spermatozoa it had an opposite, enhancing effect.
      Interpreting these results in the light of data from studies by others on a
      variety of cell types, it is proposed that swelling-activated potassium channels
      are involved in regulatory volume decrease in both species of spermatozoa, but
      that boar spermatozoa may contain fewer swelling-activated chloride channels than
      do bull spermatozoa.

PMID- 11467985
TI  - Hunting the magic bullet in immunotherapy: new forms of old treatment or
      something completely different?

PMID- 11467986
TI  - Laboratory-based allergy diagnosis: should we go with the flow?

PMID- 11467987
TI  - Development of cow's milk allergy in breast-fed infants.

PMID- 11467988
TI  - Immunotherapy with a calcium phosphate-adsorbed five-grass-pollen extract in
      seasonal rhinoconjunctivitis: a double-blind, placebo-controlled study.
AB  - BACKGROUND: Calcium phosphate-adsorbed allergen extracts are used for
      subcutaneous immunotherapy to avoid the use of aluminium adjuvants. OBJECTIVES: A
      double-blind, placebo-controlled study was performed in order to confirm the
      safety and assess the efficacy of a standardized five-grass-pollen extract
      adsorbed onto calcium phosphate for specific immunotherapy (IT). METHODS: Twenty
      nine patients with seasonal rhinoconjunctivitis were randomized to receive either
      the active preparation (16 patients) or placebo (13 patients), in a 1-year study.
      During the increasing dose phase, an extract ranging from 0.1 IR per ml to 50 IR
      per ml was administered at a rate of one subcutaneous injection per week until a
      maintenance dose was reached. The patients were assessed by symptom diary and
      rescue medications during seasonal exposure and specific nasal and skin
      reactivity before and after IT. Immunological parameters (specific IgE and IgG4
      antibodies) were assessed before, during and after IT. RESULTS: The overall
      symptoms score (mean AUC) was not significantly different between the IT group
      and the placebo group during grass-pollen exposure (49.6 vs. 56, respectively).
      The total medication score (mean AUC) was significantly lower in the IT group
      than in the placebo group (11 vs. 41, P < 0.01, Mann-Whitney U-test). The
      cumulative symptom/medication score was significantly lower in the IT group than
      in the placebo group (64.5 vs. 102.3, P < 0.05, U-test). A significant increase
      in nasal reactivity threshold was observed after IT in the IT group (21. 4 IR/mL
      before IT vs. 63.4 IR/mL after IT, P < 0.01, Wilcoxon), whereas no significant
      changes were observed in the placebo group (31.0 IR/mL before IT vs. 37.7 IR/mL
      after IT). IT induced a significant reduction in grass pollen cutaneous
      reactivity in the actively treated group (P < 0.001). A significant increase in
      serum-specific IgG4 antibody response was observed in the IT group (3.1% before
      IT vs. 10.1% after IT, P < 0.001). Nine patients in the IT group developed
      moderate immediate systemic reactions vs. two patients in the placebo group.
      CONCLUSION: Specific immunotherapy with calcium phosphate-adsorbed standardized
      grass pollen extract was safe and effective for the treatment of patients with
      seasonal allergic rhinoconjunctivitis.

PMID- 11467989
TI  - Selective development of a strong Th2 cytokine profile in high-risk children who
      develop atopy: risk factors and regulatory role of IFN-gamma, IL-4 and IL-10.
AB  - BACKGROUND: The immunological processes in early life and their relation to
      allergic sensitization leading to a Th2 cytokine profile are still not well
      understood. OBJECTIVE: To analyse the environmental and genetic risk factors and
      immunological responses at birth in relation to the development of atopic disease
      at 12 months of age in a longitudinal study of high-risk children. METHODS: High
      risk children were followed from birth till 12 months of age. Mononuclear cells
      obtained at birth and 6 and 12 months thereafter were analysed for their
      proliferative and cytokine responses after polyclonal and allergen-specific
      stimulation. RESULTS: At 12 months of age 25% children had developed an atopic
      disease. Two atopic parents, parental smoking and atopic dermatitis of at least
      one of the parents were significant risk factors. In cord blood of newborns who
      developed atopy, an increased percentage of CD4+CD45RO+ cells and an increased
      polyclonal-stimulated proliferation were observed. Furthermore, an impaired
      allergen-induced, but not polyclonal-stimulated IFN-gamma production was found,
      suggesting a regulatory defect. At 6 and 12 months of age, a strong Th2 profile
      (characterized by increased levels of IL-4, IL-5, and IL-13) after both
      polyclonal and, to a lesser extent, allergen-specific stimulation was found in
      the children developing atopy. Allergen-induced IL-10 production at 12 months of
      age was only observed in the non-atopic children. CONCLUSION: Our data indicate
      that the first 6 months of life represent a critical time window for the
      initiation of immunological changes resulting in the development of atopy. The
      selective development of a Th2 cytokine profile in high-risk children who develop
      atopy is due to increased production of Th2 cytokines, possibly caused by
      impaired allergen-induced IFN-gamma production in the neonatal period.
      Furthermore, the decreased allergen-induced IL-10 levels observed in the atopic
      children at 12 months of age may result in a lack of down-regulation of the
      inflammatory process.

PMID- 11467990
TI  - Allergen-induced basophil activation: CD63 cell expression detected by flow
      cytometry in patients allergic to Dermatophagoides pteronyssinus and Lolium
      perenne.
AB  - BACKGROUND: In this study, we determined by flow cytometry the percentage of
      basophils activated after in vitro stimulation by allergens and expressing the
      CD63 marker. The diagnostic reliability of the technique was assessed as well as
      its correlation with other in vitro diagnostic parameters. METHODS: Fifty-three
      patients suffering from asthma and/or allergic rhinitis following sensitization
      to Dermatophagoides pteronyssinus and 51 patients sensitized to Lolium perenne
      were investigated. Twenty-four atopic patients not sensitive to these allergens
      and 38 healthy subjects were also selected as controls. The basophil activation
      test determines the percentage of basophils which express CD63 as an activation
      marker, by means of flow cytometry, after in vitro stimulation with allergen,
      using double labelling with monoclonal antibody anti-CD63-PE and anti-IgE-FITC.
      RESULTS: No differences in basal values (non-activated control) were found
      between sensitized patients, atopic controls and healthy controls. On the other
      hand, sensitized patients showed a significantly higher percentage of activated
      basophils after stimulation by allergens in vitro than both control groups (P <
      0.001). We found a significant correlation between skin tests and basophil
      activation tests (r = 0.72, P < 0.001). We also found a positive and significant
      correlation between basophil activation tests and histamine release tests (r =
      0.80, P < 0.001), allergen-specific sulphidoleukotriene production (r = 0.7, P <
      0.001) and the occurrence of serum allergen-specific IgE (r = 0.71, P < 0.001).
      CONCLUSION: The basophil activation test is a highly reliable technique in the
      diagnosis of allergy to inhalant allergens. The sensitivity of the basophil
      activation test was 93.3%, and its specificity 98.4%, when using a cut-off point
      of 15% activated basophils as positive result.

PMID- 11467991
TI  - Opiate-sensitivity: clinical characteristics and the role of skin prick testing.
AB  - BACKGROUND: The value of skin prick testing in opiate-sensitive individuals is
      uncertain as opiates cause non-specific weals by direct degranulation of mast
      cells. OBJECTIVE: To define whether skin prick test (SPT) responses to opiates in
      opiate-sensitive individuals are different to those seen in the normal population
      and to describe the clinical characteristics of this group of subjects. METHODS:
      The SPT responses of eight opiate-sensitive subjects to morphine 10 mg/mL,
      pethidine (meperidine) 50 mg/mL and papaveretum 15.4 mg/mL at four different
      concentrations (undiluted, 1/10, 1/50 and 1/100) were compared with the responses
      of 100 (32 atopic) non-opiate-sensitive control subjects. Four of the opiate
      sensitive subjects had a clinical history of asthma, rhinitis or urticaria on
      occupational exposure to morphine. One subject developed urticaria with codeine,
      one developed urticaria and asthma with morphine and diamorphine and two subjects
      reacted to intravenous papaveretum with anaphylaxis or urticaria. Five out of the
      eight cases had opiate sensitivity confirmed by single-blind placebo-controlled
      oral challenge. RESULTS: Skin prick tests to all three opiates were not
      significantly different when the eight opiate-sensitive subjects were compared
      with either the entire normal control group or the subgroup of 47 definite opiate
      tolerant controls that had previously received opiates for clinical indications.
      Furthermore, there were no significant differences in size of opiate SPT
      responses between atopic and non-atopic control subjects. In the control
      subjects, there was a positive correlation in SPT weal size between the three
      opiates. CONCLUSION: Skin prick testing is not useful in the diagnosis of opiate
      sensitivity and placebo-controlled challenge should be considered.

PMID- 11467992
TI  - Serum albumins are the major site for in vivo formation of hapten-carrier protein
      adducts in plasma from humans and guinea-pigs exposed to type-1 allergy inducing
      hexahydrophthalic anhydride.
AB  - BACKGROUND: Organic acid anhydrides (OAAs) are highly allergenic compounds used
      in the chemical industry. The OAAs probably act as haptens but the proteins that
      form conjugates with OAAs in vivo are still unknown. Conjugates between the
      anhydrides and serum albumins (SAs) have routinely been used when testing for OAA
      specific antibodies. However, the use of SA as the carrier-protein in these tests
      has never been evaluated. OBJECTIVE: The aim of this study was to identify major
      and also immunologically relevant protein conjugates of a particularly
      sensitizing OAA, hexahydrophthalic anhydride (HHPA), in plasma. METHODS: Plasma
      was obtained from a HHPA-exposed worker, from a guinea-pig (GP) exposed to HHPA
      in an exposure chamber for 2 weeks (8 h/day, 5 days/week) and from a GP exposed
      once, nose-only, to tritium-labelled HHPA for 8 h. The plasma was fractionated
      using ion exchange chromatography and gel filtration. These fractions and also
      aliquots of unfractioned plasma were hydrolysed, derivatized and analysed for
      anhydride adduct content using gas chromatography-mass spectrometry. Further,
      plasma from the tritium labelled HHPA-exposed GP was separated by SDS gel
      electrophoresis and analysed by autoradiography. In addition, immunologically
      relevant proteins were identified through specific IgE and IgG immunoblottings
      using sera from exposed workers. RESULTS: For humans > 85% and for GPs > 74% of
      the HHPA-adducts coeluted with SA in plasma. Autoradiography of GP-plasma shows a
      single 66 kDa protein that binds HHPA. IgE immunoblotting shows a major 66 kDa
      and a minor 28 kDa protein which could be inhibited by HHPA-SA conjugate. IgG
      immunoblotting showed a major 66 kDa protein and several minor protein bands.
      CONCLUSION: This study shows SA to be the major protein in plasma that forms
      adducts in vivo with HHPA. The results also show that in an in vitro synthesized
      HHPA plasma protein conjugate, HHPA-specific IgE and IgG antibodies bind
      preferably to the SA.

PMID- 11467993
TI  - Reducing the need for food allergen challenges in young children: a comparison of
      in vitro with in vivo tests.
AB  - BACKGROUND: Double-blind placebo-controlled food challenges (DBPCFC), the gold
      standard for the diagnosis of food hypersensitivity, are time-consuming and not
      without risk. We have recently reported skin prick test (SPT) weal diameters to
      cow's milk, egg and peanut above which infants and young children referred for
      investigation of suspected food allergy showed an adverse reaction on food
      challenge. We have termed these the "100% diagnostic SPT levels". In this study,
      we compare in vivo with in vitro measurement of IgE antibody levels to three
      common food allergens--cow's milk, egg and peanut--in infants and young children
      with suspected food allergy, in order to reduce the need for food challenges.
      METHODS: SPT and Enzyme Allergo-sorbent Test (EAST) (from 1992 to 1998) and CAP
      values (from 1999 to 2000) were performed in 820 children < 2 years of age with
      suspected allergy to cow's milk and/or egg and/or peanut. SPT levels previously
      shown to be diagnostic of challenge-proven allergy to cow's milk, egg and peanut
      were used as the "100% diagnostic SPT levels" and compared with EAST and CAP
      values associated with IgE food allergy according to the manufacturer's
      definition. RESULTS: McNemar's test showed a significant difference between the
      "100% diagnostic SPT levels" and positive EAST in identifying patients who did
      not require food challenge for cow's milk (P = 0.01), egg (P < 10-6) and peanut
      (P < 10-6), and a significant difference between the "100% diagnostic SPT levels"
      and positive CAP (P < 10-6) for egg and peanut but not cow's milk. Twenty-three
      per cent of food challenges which, based on the results of EAST and CAP, would
      have been necessary to confirm the diagnosis of food allergy were avoided by the
      use of the "100% diagnostic SPT levels" . CONCLUSION: The use of the "100%
      diagnostic SPT levels" compared with in vitro measurement of IgE antibody to
      cow's milk, egg and peanut reduces the need for food challenge in young children
      with suspected food allergy.

PMID- 11467994
TI  - Serum interleukin-5 in aspirin-induced asthma.
AB  - BACKGROUND: Eosinophilopoetic cytokine IL-5 enhances cysteinyl-leukotriene (cys
      LT) synthesis in eosinophils in vitro. In patients with aspirin-induced asthma
      (AIA) bronchial biopsies revealed eosinophil infiltration and a marked increase
      in IL-5 positive cells. OBJECTIVE: We wondered whether in AIA patients the
      bronchial IL-5 increase is reflected in peripheral blood, and if so, whether it
      is related to overproduction of cys-LT. METHODS: In 11 stable patients with AIA,
      32 with ATA (aspirin-tolerant asthma) and in 16 controls we measured serum IL-5
      concentrations and urinary LTE4, believed to reflect global cys-LT production.
      RESULTS: Serum IL-5 was detectable in 12 of 43 asthmatics, but in none of the
      control subjects. It was highest in the ATA group and differed significantly from
      the controls. There was no significant difference in IL-5 levels between: (i) the
      asthmatic groups studied, and (ii) AIA patients and controls. No relationship was
      found between serum IL-5 and urinary cys-LT. CONCLUSION: Overexpression of IL-5
      reported in the airways of aspirin-sensitive patients with asthma was not
      reflected in their blood. If IL-5 affects cys-LT production, it is rather in the
      bronchi of the patients than in the blood.

PMID- 11467995
TI  - Isolated airways from current smokers are hyper-responsive to histamine.
AB  - Epidemiological studies suggest that bronchial hyper-responsiveness (BHR) and
      elevated levels of serum IgE are more frequently found in current smokers than in
      ex-smokers. Since elevated serum IgE is associated with BHR under both in vivo
      and in vitro conditions, we aimed to assess whether smoking affects BHR
      independently from IgE. Lung resection material was obtained from 27 current
      smokers and 11 non-smokers with low serum IgE (< 100 U/mL). Peripheral airways
      were cut into rings and incubated overnight in the presence (passively
      sensitized) or absence (non-sensitized) of serum containing IgE levels above 250
      U/mL. Isometric contractile responses to histamine were assessed in the organ
      bath. Compared with non-smokers, isolated airways from smokers showed
      significantly increased responses to histamine (P < 0.05, ANOVA). Passive
      sensitization enhanced responses in both groups by about the same amount (P <
      0.05, both). In patients with low serum IgE current smoking is associated with
      increased bronchial responsiveness to histamine in vitro, which can be further
      enhanced by passive sensitization. These findings suggest that both smoking and
      serum IgE contribute to non-specific airway hyper-responsiveness.

PMID- 11467996
TI  - Induction, distribution and modulation of upper airway allergic inflammation in
      mice.
AB  - BACKGROUND: To further elucidate mechanisms of human allergic rhinosinusitis, we
      studied the induction, distribution and modulation of allergen-induced upper
      airway inflammation in a BALB/c mouse model. METHODS: Allergic inflammation
      induced with ovalbumin (OVA) by intraperitoneal (IP) injection in alum was
      compared to repeated intranasal instillation. The type and distribution of
      inflammatory cells was compared in the respiratory and olfactory epithelial
      compartments. Eosinophil distribution was assessed using Scarlet Red stain and a
      polyclonal antibody recognizing eosinophil major basic protein (MBP). The role of
      interleukin (IL)-5 in upper airway inflammation was tested by administration of
      polyclonal anti-IL-5 antibody during the sensitization protocol. RESULTS:
      Unsensitized control mice receiving saline failed to develop upper airway
      eosinophil infiltration. IP OVA-sensitized mice developed marked upper airway
      mucosal eosinophil infiltration after aerosol OVA challenge, whereas repeated
      intranasal instillation of OVA produced qualitatively similar, but less intense
      eosinophil infiltration. Using either sensitization protocol, eosinophil
      infiltration was seen in areas of the lower portion of the nasal septum, the
      floor and the lower lateral walls of the mid-caudal region of the nasal cavity.
      Immunofluorescence staining for MBP confirmed this distribution of eosinophils
      but also demonstrated some eosinophils in the maxillary sinuses and in
      circumscribed regions of the ethmoturbinates. All areas of eosinophil
      infiltration were lined by respiratory epithelium. The selective infiltration of
      respiratory but not olfactory epithelium by eosinophils was unassociated with a
      measurable induction of epithelial ICAM-1 or eotaxin expression. OVA-induced
      upper airway eosinophil infiltration was found to be IL-5 dependent, since
      administration of a polyclonal anti-IL-5 antibody (TRFK-5) during OVA
      sensitization resulted in a marked modulation (80% decrease) in eosinophil
      infiltration in response to subsequent OVA challenge. CONCLUSION: The mouse upper
      airway, specifically in areas containing respiratory epithelium, is a target for
      OVA-induced allergic inflammation. This selective infiltration of respiratory,
      but not olfactory, epithelium is, in part, dependent upon IL-5. This model is
      useful for further dissection of the inflammatory response with genetic
      manipulations and targeted immunological approaches.

PMID- 11467997
TI  - Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial
      epithelial cells.
AB  - BACKGROUND: Human rhinoviruses (RVs) are the most common precipitants of asthma
      exacerbations. RV infection of bronchial epithelium results in local airway
      inflammation inducing eosinophil recruitment and activation. Induction of
      eosinophil chemoattractants could represent a central mechanism, as well as a
      prime target for intervention. OBJECTIVE: To assess the effect of RV infection on
      mRNA expression and production of eosinophil chemoattractants by bronchial
      epithelial cells in-vitro. METHODS: BEAS-2B cells were infected with major and
      minor RVs and the mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin, eotaxin
      2, MCP-2, MCP-3 and MCP-4 was assessed by reverse transcription PCR. In cases
      where mRNA induction was observed, a fluoroimmunoassay was used to confirm
      protein production. To assess the virus-specificity of the observed reactions,
      cells were also exposed to inactivated RVs. RESULTS: RV infection was able to up
      regulate mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin and eotaxin-2, did
      not affect MCP-4, while MCP-2 and MCP-3 were not expressed either at baseline or
      after virus infection. Protein production was confirmed for IL-8, RANTES and
      eotaxin, but not for MIP-1alpha. When RVs were inactivated cytokine up-regulation
      was almost completely lost. CONCLUSION: Infection of bronchial epithelial cells
      with RVs results in the production of a wide array of mediators that are able to
      chemoattract eosinophils. These include the eosinophil-specific molecules eotaxin
      and eotaxin-2, in addition to IL-8 and RANTES, which are the most abundant.
      Eosinophil recruitment after RV infection of bronchial epithelium could represent
      a central event in the pathogenesis of virus-induced asthma exacerbations.

PMID- 11467998
TI  - Importance of inflammatory and immune components in a mouse model of airway
      reactivity to toluene diisocyanate (TDI).
AB  - BACKGROUND: Nearly 9 million individuals are exposed to agents in the workplace
      associated with asthma, and isocyanates represent the most common cause of
      occupationally induced asthma. OBJECTIVES: Nonetheless, the immunological
      mechanisms responsible for isocyanate-induced asthma are not clear. A murine
      model for toluene diisocyanate (TDI) asthma is described and employed to examine
      inflammatory and immune components that may be involved in the disease. METHODS:
      Groups (n = 6) of C57BL/6J and athymic mice were sensitized by subcutaneous
      injection (20 microl on day 1, 5 microl on days 4 and 11), and 7 days later
      challenged by inhalation (100 p.p.b., days 20, 22 and 24) with TDI. Twenty-four
      hours following the last challenge the tracheae and lungs were examined for
      histological changes as well as for the expression of Th1, Th2 and pro
      inflammatory cytokines. Mice were also examined for airway reactivity to
      methacholine challenge and for specific and total IgE and IgG antibodies.
      RESULTS: TDI sensitization resulted in increased reactivity to methacholine
      challenge as well as a significant inflammatory response in the trachea and nares
      of wild-type mice, but not in the athymic mice nor in the lungs of the C57BL/6J
      mice. Airway inflammation was characterized by inflammatory cell influx, goblet
      cell metaplasia and epithelial damage. Histological changes in the trachea were
      accompanied by increased mRNA expression of interleukin (IL)-4, tumour necrosis
      factor alpha, lymphotoxin beta, lymphotactin and Rantes, as well as TDI-specific
      IgG antibodies and elevated levels of total IgE. IgE-specific antibodies were not
      detected with this exposure regimen but were produced when the TDI concentrations
      were increased. CONCLUSIONS: These studies provide a unique murine model for
      occupational asthma that generates both inflammatory and immune mediators similar
      to those occurring in TDI-induced asthma in humans.

PMID- 11467999
TI  - IL-6 attenuates apoptosis, while neither IL-6 nor IL-10 affect the numbers or
      protease phenotype of fetal liver-derived human mast cells.
AB  - BACKGROUND: The combination of recombinant human stem cell factor (rhSCF), rh
      interleukin (IL)-6 and rhIL-10 was reported to be optimal for mast cell
      development from cord blood progenitors and to induce chymase expression in all
      such mast cells earlier in their development than tryptase. OBJECTIVE: The
      effects of rhIL-6 and rhIL-10 in various combinations on the rhSCF-dependent
      development of human mast cells from fetal liver progenitors were examined in
      serum-free media. METHODS: Dispersed fetal liver cells were cultured in serum
      free AIM-V medium with rhSCF alone, or with combinations of rhIL-6 and rhIL-10.
      Tryptase and chymase expression, surface Kit expression, metachromasia with
      toluidine blue and apoptosis were measured. RESULTS: Neither rhIL-6 nor rhIL-10
      nor the two interleukins together, when included from day 0 of culture, affected
      the number or protease phenotype of mast cells at 1 or 3 weeks. Expression of
      tryptase paralleled the appearance of metachromasia and surface Kit, both of
      which preceded chymase expression, regardless whether a rabbit polyclonal or
      mouse monoclonal anti-chymase antibody preparation was used. On the other hand,
      rhIL-6 markedly attenuated baseline levels of apoptosis in the presence of rhSCF
      as well as apoptosis occurring after withdrawal of rhSCF, whereas rhIL-10 had no
      effect. CONCLUSION: RhIL-6 protected fetal liver-derived mast cells from
      apoptosis, particularly after withdrawal of rhSCF, but neither rhIL-6 nor rhIL-10
      nor the combination of these interleukins affected the numbers or protease
      phenotype of these mast cells.

PMID- 11468000
TI  - Allergenic proteins are fragmented in low concentrations of sodium hypochlorite.
AB  - BACKGROUND: To facilitate allergen removal from indoor environments, it would be
      helpful to have household cleaning products that modified allergenic activity.
      Because NaOCl dissolves proteins in high concentrations and is both capable of
      killing bacteria and viruses and inactivating viral antigens at somewhat lower
      concentrations, we explored its effects on Mus m 1 and other indoor allergens.
      OBJECTIVE: To examine the ability of NaOCl to reduce the allergenicity of Mus m 1
      and other indoor allergens. METHODS: Using purified mouse urinary allergen, we
      examined the effect on protein measured by Coomassie protein assay and on Mus m 1
      measured by ELISA. We also examined the effects using SDS/PAGE and Western blots
      probed with sheep anti-Mus m 1 and with allergic human serum. RESULTS: When NaOCl
      and Mus m 1 were combined in a molar ratio of 100 : 1, IgE binding to Mus m 1 on
      Western blot was significantly reduced. At higher NaOCl concentrations the
      protein appeared to fragment and eventually became undetectable. Fragmentation
      appeared to be random in that peptides of a wide range of apparent molecular
      weight were produced. The reaction was complete within 1-2 min at OCl : pr ratios
      of greater than 200 : 1 and was optimal at pH 7.4. Immunological activity of
      other allergens (Fel d 1, Bla g 1, Der p 1) was decreased in vitro and dried
      allergen extracts were removed from surfaces. Adding an extraneous protein, BSA,
      to NaOCl:Mus m 1 solutions decreased the effect of NaOCl on the allergen.
      CONCLUSIONS: We concluded that NaOCl at concentrations commonly used in household
      products is capable of dramatically affecting allergenic protein.

PMID- 11468001
TI  - Increased expression of cytosolic phospholipase A2, 5-lipoxygenase and 5
      lipoxygenase-activating protein in rat peritoneal macrophages during ovalbumin
      induced sensitization.
AB  - BACKGROUND: Macrophages are involved in immediate hypersensitivity reactions by
      their ability to release leukotrienes involved in the symptomatology of allergy.
      To date it is unknown whether this ability to secrete leukotrienes has been
      favoured by modifications, occurring during the sensitization phase, of the
      enzymes involved in leukotriene metabolism. OBJECTIVE: We used ovalbumin
      sensitized rats to study the expression of cytosolic phospholipase A2 (cPLA2), 5
      lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in peritoneal
      macrophages during active sensitization. We compared basal and challenged (PMA,
      A23187 and allergen) arachidonic acid (AA) metabolism of macrophages from control
      (cPM) and sensitized (sPM) rats. Then we tested, in cultured cPM, whether IL-4,
      the predominant cytokine of sensitization process, could reproduce the enzymatic
      modifications occurring in macrophages during sensitization. METHODS: cPLA2, 5-LO
      and FLAP expression was assessed by Western blotting. The arachidonic acid (AA)
      metabolism study was performed after incorporation of tritiated AA in macrophages
      and analysis of secreted tritiated eicosanoids. RESULTS: Ovalbumin-sensitization
      of rats increased cPLA2, 5-LO and FLAP expression in peritoneal macrophages.
      These increased expressions were not paralleled by modifications of basal and PMA
      or A23187-stimulated AA metabolism of sPM. However, when macrophages encountered
      the specific allergen for a second time, sPM secreted higher levels of
      leukotrienes than cPM. IL-4 induced FLAP expression in cPM but had no effect on
      cPLA2 and 5-LO expression. CONCLUSION: Active sensitization of rats induces an
      increase, in peritoneal macrophages, of the enzymes involved in leukotriene
      metabolism. The increased leukotriene secretion of sPM in response to ovalbumin
      challenge may be favoured by this increased expression of cPLA2, 5-LO and FLAP
      that, however, is not able to lead to modifications of macrophage AA metabolism
      in any circumstance. Our results also suggest that IL-4 is not the major element
      originating the enzymatic modification induced by sensitization in peritoneal
      macrophages.

PMID- 11468002
TI  - Chronic urticaria: novel clinical and serological aspects.
AB  - BACKGROUND: Recently, distinct studies have shown that: (a) chronic idiopathic
      urticaria (CIU) is autoimmune in 30-50% of cases; (b) in patients with CIU the
      autologous serum skin test is inhibited by heparin; and (c) basophil histamine
      release induced in vitro by CIU sera maybe complement-dependent. OBJECTIVE: To
      carry out a comprehensive clinical and serological study on CIU based upon these
      observations. METHODS: Three hundred and six adults with CIU underwent
      intradermal (ID) test with autologous serum; 57 of them with autologous
      heparinized plasma as well. Sera from 121 patients (plasmas from 17) were
      employed to induce in vitro histamine release from basophils of normal donors.
      The effects of heating (56 degrees C, 60 min), filtration through membrane, and
      preincubation with heparin were evaluated as well. RESULTS: Autologous serum and
      plasma induced a weal and flare reaction in 205 out of 306 (205/306; 67%) and in
      8/57 (14%) patients, respectively. Positive plasma skin tests were observed only
      in patients showing strongly positive serum skin tests. Plasma did not elicit any
      skin reaction in 3/3 patients with dermatographism who showed a positive
      intradermal test with saline. Sera from 20/121 (16.5%) patients induced
      significant histamine release from basophils of normal donors. 19/20 sera were
      from patients with a positive intradermal test; thus, basophil histamine release
      assay was positive in 19/87 (21.8%) patients with a positive serum skin test.
      Heating at 56 degrees C x 1 h markedly reduced the histamine-releasing activity
      of both serum and plasma from in vitro reactors. Ultrafiltered fractions > 100
      kDa of both sera tested retained the histamine-releasing activity, whereas
      fractions < 100 kDa were not able to induce any histamine release. Heparin dose
      dependently inhibited histamine release induced by sera and plasma, and by
      basophil agonists such as anti-IgE, formyl-methionyl-leucyl-phenilalanine, and
      interleukin (IL)-3. CONCLUSIONS: 67% of our patients with CIU showed a positive
      autologous serum skin test. Sera from about 20% of those positive on autologous
      serum skin test induced histamine release from normal basophils in vitro probably
      as a consequence of the presence of functional autoantibodies. The marked
      difference between in vivo and in vitro findings could reflect the existence of a
      mast cell-specific histamine-releasing factor which does not release histamine
      from basophils of healthy blood donors. However, it might be also the result of
      in vivo priming of patients' cutaneous mast cells or of heterogeneity of basophil
      donors. At least in some cases complement seems essential for histamine-releasing
      activity of serum from patients with CIU. Heparin inhibits histamine release from
      both basophils (in vitro) and mast cells (in vivo), probably acting directly at a
      cellular level.

PMID- 11468003
TI  - Repeatability and validity of cell and fluid-phase measurements in nasal fluid: a
      comparison of two methods of nasal lavage.
AB  - BACKGROUND: There is little information on the repeatability of cell counts and
      fluid-phase measurements in nasal fluid obtained by different methods of nasal
      lavage. OBJECTIVE: To compare the repeatability and validity of total and
      differential cell counts and eosinophil cationic protein (ECP) in nasal
      secretions obtained by two methods of nasal lavage. PATIENTS AND METHODS: Twelve
      healthy subjects and twelve subjects with clinically stable allergic rhinitis
      were randomly assigned to two nasal lavages (separated by 48 h), by one of two
      methods in the first week and by the second method in the following week. One
      method was a modification of the method described by Greiff et al. and Grunberg
      and coworkers and the other was that described by Naclerio and coworkers.
      RESULTS: Both methods of nasal lavage gave poorly repeatable eosinophil counts
      and ECP in normal subjects but better repeatability in subjects with rhinitis.
      The modified Greiff/Grunberg method gave higher and more repeatable total cell
      count and, in subjects with rhinitis, more reproducible ECP levels compared with
      the Naclerio METHOD: Both methods were able to discriminate between healthy and
      rhinitic subjects: mean +/- SD eosinophil percentage count and eosinophil
      cationic protein differences were 4.5 +/- 4% (P < 0.05) and 24.5 +/- 46.9
      microg/L (P < 0.05), respectively, with the modified method and 7.0 +/- 4% (P <
      0.05) and 26.9 +/- 68 microg/L (P < 0.05), respectively, with the Naclerio
      method. CONCLUSION: Both methods are valid and discriminate between normal and
      rhinitic subjects. In subjects with rhinitis, although the repeatability of
      eosinophil counts is similar by both methods, the modified Greiff/Grunberg method
      gives more reproducible ECP measurements, compared with the Naclerio method.

PMID- 11468004
TI  - An annexin 1 (ANXA1)-derived peptide inhibits prototype antigen-driven human T
      cell Th1 and Th2 responses in vitro.
AB  - BACKGROUND: Annexin-1 (ANXA1, lipocortin 1) is a pleiotrophic protein produced by
      many cell types including peripheral blood leucocytes. Although it has been shown
      to inhibit "macroscopic" inflammatory processes in animal models, its direct
      effects on antigen-activated human T cells have not been studied. OBJECTIVE: To
      test the hypothesis that ANXA1-derived peptides inhibit antigen-driven prototype
      Th1 and Th2-type human T cell responses of clinical relevance and lectin-driven
      responses in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were
      isolated from 14 atopic subjects sensitized to house dust mite allergen
      (Dermatophagoides pteronyssinus, Der p) and purified protein derivative (PPD) of
      Mycobacterium tuberculosis. PBMC (1 x 106/mL) were cultured with
      phytohaemagglutinin (PHA; 5 microg/mL; 4 days), Der p (25 microg/mL; 6 days), PPD
      (10 microg/mL, 6 days) or medium control. Two ANXA1-derived peptides, Ac2-26 and
      AF-2 (5-500 microM), were assessed for possible inhibition of PHA-and antigen
      induced T cell proliferation (measured by 3H-thymidine uptake), while Ac2-26 was
      assessed for inhibition of Der p-induced interleukin (IL)-5 release and PPD
      induced interferon-gamma (IFN-gamma) release (measured by ELISA). Comparison was
      made with dexamethasone as an established inhibitory control. Endogenous
      production by PBMC of cell surface-associated and intracellular ANXA1 in response
      to PHA, Der p and PPD in the presence and absence of dexamethasone was measured
      by specific ELISA. RESULTS: Both PHA- and antigen-induced T cellular
      proliferation were inhibited by dexamethasone. Although neither ANXA1-derived
      peptide significantly altered PHA-induced proliferation, both effected
      concentration-dependent reductions in antigen-induced proliferation, Ac2-26 being
      the more potent. Peptides of identical amino acid composition to Ac2-26 and AF-2,
      but of random sequence, were ineffective at equivalent concentrations. In
      addition, Ac2-26 and dexamethasone inhibited Der p-induced IL-5 release and PPD
      induced IFN-gamma release in a concentration-dependent fashion. Endogenous ANXA1
      was detectable in PBMC, but at concentrations approximately 104-fold lower, in
      molar terms, than the effective concentrations of the exogenously added, ANXA1
      derived inhibitory peptides. Endogenous production was not significantly altered
      by any of the T cell stimuli employed in this study, in the presence or absence
      of dexamethasone. CONCLUSION: In prototype Th1 and Th2-type human T cell
      responses, ANXA1-derived peptides can inhibit antigen-driven cellular
      proliferation and cytokine production.

PMID- 11468005
TI  - Identification of beta-lactoglobulin-derived peptides and class II HLA molecules
      recognized by T cells from patients with milk allergy.
AB  - BACKGROUND: Cow's milk allergy impairs the health and development of many infants
      since it deprives them of adequate nutrition. Cow's milk fractions contain many
      allergens, and beta-lactoglobulin (BLG) is one of the major allergens. OBJECTIVE:
      The purpose of this study was to determine T cell epitopes, antigen-presenting
      molecules and cytokine production by T cells in relation to BLG. The results can
      provide new therapeutic possibilities of using analogue peptides of BLG for
      infants with cow's milk allergy. METHODS: Using a mixture of a panel of
      overlapping synthetic peptides that cover the entire BLG molecule, we established
      polyclonal BLG-specific short-term T cell lines and clones from peripheral blood
      mononuclear cells of four patients with allergy to cow's milk carrying most of
      the common human leucocyte antigen (HLA) haplotypes seen in the Japanese
      population. We then identified the T cell epitopes and antigen-presenting
      molecules, and measured the production of cytokines interleukin (IL)-4, IL-5 and
      interferon-gamma in the culture supernatants. RESULTS: The T cell lines
      established from the four patients responded to seven different peptides. Three
      of the peptides stimulated the T cells of two donors, regardless of the HLA
      types. The patterns of inhibition of the proliferative responses of the cell
      lines by anti-HLA class II antibodies were heterogeneous; three were mainly
      inhibited by anti-HLA-DR mAbs, and the other was inhibited by anti-HLA-DQ mAbs.
      High levels of IL-5 were produced by these T cell lines. CONCLUSIONS: Patients' T
      cells recognized BLG in association with a variety of HLA-DR or -DQ as antigen
      presenting molecules. Although some peptides did have a more potent T cell
      stimulatory activity than others, the T cell receptor ligands formed with the BLG
      molecule are heterogeneous. Peptides for the desensitization of T cells of the
      patients with cow's milk allergy need to be designed keeping in mind the
      different requirements in different ethnic groups.

PMID- 11468006
TI  - Eosinophils are activated in middle ear mucosa and middle ear effusion of
      patients with intractable otitis media associated with bronchial asthma.
AB  - BACKGROUND: Although patients with intractable otitis media associated with
      bronchial asthma have extensive accumulation of eosinophils in the middle ear
      mucosa and middle ear effusion, systematic histological and immunohistochemical
      studies have not been performed. OBJECTIVES: To clarify the pathogenesis of
      middle ear diseases, we carried out immunohistochemical studies on middle ear
      specimens, particularly focusing on the characteristics of accumulated
      eosinophils. METHODS: Middle ear specimens obtained from eight adult patients and
      from 17 controls were immunohistochemically stained using monoclonal antibodies
      against EG1, EG2, mast cell tryptase, IgA and IgE. The concentration of
      eosinophil cationic protein (ECP) in middle ear effusion samples was also
      measured. RESULTS: In the asthmatic patients, severe round-cell infiltration was
      observed in the submucosa and most of the EG1-positive cells were also EG2
      positive. In the control patients, the mucosa showed a fibrotic change with a few
      inflammatory cells, and EG1- or EG2-positive cells were quite few. The expression
      of IgE was found not only on the surface of mast cells but also within the plasma
      cells in the asthmatic patients, and the number of IgE-positive cells was about
      twice as high as that of mast cells. A significantly higher concentration of ECP
      was noted in middle ear effusion obtained from the asthmatic patients than that
      from the control patients. CONCLUSION: Most of the eosinophils in the middle ear
      mucosa and middle ear effusion were activated, resulting in degranulation and
      release of ECP, and local IgE production occurs in the middle ear mucosa,
      indicating that the intractable inflammation is closely associated with IgE
      mediated late phase response with eosinophil accumulation.

PMID- 11468007
TI  - Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic,
      noncholinergic mechanism.
AB  - The contribution of NO-cGMP dependent pathway to phentolamine mesylate-evoked
      nonadrenergic, noncholinergic relaxation of rabbit corpus cavernosum was
      investigated in vitro. Stimulation of nonadrenergic, noncholinergic neurons of
      the rabbit corpus cavernosum elicited frequency-related relaxation that was
      significantly attenuated by L-NAME (NO synthase inhibitor) or ODQ (an inhibitor
      of guanylate cyclase). Moreover, tetrodotoxin, a sodium channel blocker,
      abolished the electrical field stimulation-induced relaxation of rabbit corpus
      cavernosum, suggesting that neuronal release of NO mediates relaxation to
      electrical field stimulation. Phentolamine mesylate (30 and 100 nM) dose
      dependently enhanced electrical field stimulation-induced relaxation of the
      rabbit corpus cavernosum. Prazosin (30 microM) and yohimbine (30 microM) failed
      to affect phentolamine mesylate-mediated nonadrenergic, noncholinergic rabbit
      penile smooth muscle relaxation, suggesting that phentolamine relaxes rabbit
      corpus cavernosum independent of alpha-adrenergic receptor blockade. In contrast,
      pretreatment of the rabbit cavernosal strips with L-NAME significantly-attenuated
      electrical field stimulation produced relaxations to phentolamine mesylate,
      suggesting that phentolamine mesylate relaxes rabbit corpus cavernosum by
      activating NO synthase. The data suggest that phentolamine mesylate relaxes
      nonadrenergic noncholinergic neurons of the rabbit corpus cavernosum by
      activating NO synthase and is independent of alpha-adrenergic receptor blockade.

PMID- 11468008
TI  - Cardiac cellular actions of hydrochlorothiazide.
AB  - In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ)
      lower blood pressure by decreasing peripheral resistance rather than by their
      diuretic effect. This action has been attributed to the opening of Ca2+-activated
      K+ channels in vascular smooth muscle cells. However, little is known about their
      cardiac cellular actions. Here we investigated the possible actions of HCTZ on
      action potential and contraction of rat ventricular muscle strips and on the
      ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed
      ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM).
      Action potential duration at -60 mV and maximal rate of depolarization were,
      however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At
      the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and
      the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL
      were not voltage-or frequency-dependent. In cells intracellularly perfused with
      50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient
      (Ito), the delayed rectifier and the inward rectifier potassium currents were
      decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent.
      In conclusion, HCTZ at high concentrations possesses a negative inotropic action
      that could be in part due to its blocking action on INa and ICaL. The actions of
      HCTZ on multiple cardiac ionic currents could explain its weak effect on action
      potential duration.

PMID- 11468009
TI  - The effect of pentoxifylline on intestinal ischemia/reperfusion injury.
AB  - The small intestine is highly sensitive to oxygen free radical-induced injury.
      Post-ischemic intestinal tissue damage appears to be due to the formation of
      oxygen radicals. Free radical initiated lipid peroxidation (LP) following
      intestinal ischemia/reperfusion (I/R) may disrupt mucosal integrity. Indirectly,
      the radicals trigger the accumulation of neutrophils within the affected tissue,
      initiating inflammatory processes that lead to severe mucosal lesions. In the
      present study we investigated the effect of pentoxifylline (PTX), a potent
      inhibitor of tumour necrosis factor production, on I/R induced intestinal injury.
      Wistar albino rats were divided into four groups: (1) Sham operation (S); (2)
      Sham operation + PTX (50 mg/kg i.v.) (S + PTX); (3) 1 h ischemia + 2 h
      reperfusion (I/R); and (4) I/R + PTX. Animals were sacrificed at the end of the
      reperfusion period and ileum samples were obtained. Malondialdehyde (MDA) levels,
      an end product of LP, glutathione (GSH) levels, a key antioxidant, and
      myeloperoxidase (MPO) activity (an index of polymorphonuclear neutrophils)
      stimulation, were determined in ileum homogenates. The results of the present
      study indicate that ischemia/reperfusion results in a significant increase in MDA
      content and MPO activity with a significant decrease in GSH content. Treatment
      with PTX returns these biomarkers to control values. A mechanism of this
      protective effect may involve inhibition of neutrophil oxidative burst.

PMID- 11468010
TI  - Role of bradykinin and tachykinins in the potentiation by enalapril of coughing
      induced by citric acid in pigs.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are among the first-choice drugs
      for treating hypertension and congestive heart disease. It has been reported,
      however, that these drugs could induce chronic cough and airway
      hyperresponsiveness. The aim of this work was to assess in pigs the effects of
      bradykinin and tachykinins on citric-acid-induced coughing after ACE inhibitor
      pretreatment. Coughing was induced by challenging pigs with an aerosol of 0.8 M
      citric acid over 15 min. Coughs were counted by a trained observer for 30 min.
      The animals underwent two cough induction tests two days apart (days 1 and 3),
      the first being taken as a control. All drugs were injected intravenously 30 min
      before the second challenge. In the control group, no difference was observed
      between days 1 and 3. The ACE inhibitor enalapril (7.5 and 15 microg/kg) caused
      the cough frequency to increase significantly. In contrast, a dose-related
      decrease was observed with Hoe140 (icatibant), a bradykinin B2 receptor
      antagonist (0.5 and 1 mg/kg). When both drugs were administered simultaneously
      (15 microg/kg for enalapril and 1 mg/kg for Hoe140), a significant increase was
      observed as compared with the control value obtained on day 1. When enalapril was
      combined with the three tachykinin receptor antagonists SR 140333 (NK1 receptor
      antagonist), SR 48968 (NK2 receptor antagonist) and SR 142801 (NK3 receptor
      antagonist), a significant decrease was observed as compared with control value
      obtained on day 1; the percentage of variation was also significantly different
      as compared with those observed in enalapril groups at both doses. These data
      suggest that ACE-inhibitor-induced enhancement of the cough reflex is mainly due
      to tachykinins and not to bradykinin in our pig model. Bradykinin, however, plays
      a major role in coughing induced by citric acid alone.

PMID- 11468011
TI  - On the possible role of muscle in the pathogenesis of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a common human inherited disease characterized
      by degeneration of motoneurons and muscular atrophy. SMA results from deletions
      or mutations of the SMN (survival motor neuron) gene. A nerve-muscle coculture
      model, consisting of human muscle cells innervated by rat embryonic spinal cord
      explants, was used to study the pathogenesis of SMA. Previous studies have shown
      that myotubes formed by fusion of satellite muscle cells from patients with SMA I
      or SMA II (but not SMA III) underwent a characteristic degeneration 1-3 weeks
      after innervation. To correlate this cellular study with a molecular approach, we
      used reverse transcriptase-polymerase chain reaction (RT-PCR), and showed that
      SMN mRNAs were expressed throughout the fusion of normal satellite muscle cells
      with two peaks, the first appearing prior to the onset of fusion and the second
      one or two days before innervation. When satellite muscle cells from patients
      with SMA I or II were used, only the first peak was observed. Because in these
      cases the SMN telomeric gene (SMNtel) is deleted, it was concluded that the
      contribution of SMNtel-dependent mRNAs to the second peak is predominant in
      normal myogenesis and involved in maturation of myotubes. In addition, diseased
      satellite muscle cells did not fuse at the same rate as normal satellite muscle
      cells. Studies on myf-5, a muscle specific transcription factor family, showed
      that its expression was impaired during the fusion of satellite muscle cells from
      patients with SMA I or II compared with normal satellite muscle cells. Taken
      together, these observations suggest that (a) there is a muscle specific
      expression pattern of SMN, and (b) SMN probably plays a crucial role in
      maintenance of a functional motor unit, by allowing muscle cells to correctly
      differentiate and to allow motoneuron survival.

PMID- 11468012
TI  - S15176 and S16950 interaction with Cyclosporin A antiproliferative effect on
      cultured human lymphocytes.
AB  - S15176 and S16950 are trimetazidine derivatives that antagonize more strongly
      than the parent drug mitochondrial toxicity, which leads to cellular hypoxia and
      nephrotoxicity in kidneys experimentally exposed to cyclosporin A. We have
      investigated whether every derivative might interact or not with the inhibitory
      effect of Cyclosporin A on the proliferation of cultured human lymphocytes.
      S15176 significantly increased the antilymphoproliferative effect of Cyclosporin
      A, whereas S15176 by itself neither displayed any antilymphoproliferative effect,
      nor did it induce any apoptotic process in cultured human lymphocytes. The effect
      of S16950 was not significant.

PMID- 11468013
TI  - Biotransformation in vitro of the 22R and 22S epimers of budesonide by human
      liver, bronchus, colonic mucosa and skin.
AB  - The pharmacological effects of glucocorticoids are greatly influenced by their
      pharmacokinetic properties. In the present report, the in vitro biotransformation
      of the 22R and 22S epimers of the topical steroid budesonide was studied in the S
      9 fraction of human liver, bronchus, skin and colonic mucosa. The disappearance
      of unchanged epimers of budesonide was measured during 90 min of incubation by
      high performance liquid chromatography. The rate of disappearance was high in
      human liver while little biotransformation occurred in bronchial tissue and
      colonic mucosa, and none was detected in the skin. A marked decay of the initial
      concentration of unchanged budesonide epimers was noticed after 2 h incubation in
      cultured human hepatocytes, while only a small decrease was observed after 24 h
      incubation in cultured human airway smooth muscle cells and BEAS-2B cells. The
      22R epimer of budesonide suffered greater in vitro biotransformation than the 22S
      epimer in human hepatic, bronchial and colonic tissues. These findings extend
      those of other studies, and confirm that the high therapeutic ratio of budesonide
      is due to negligible local biotransformation combined with high level of liver
      metabolism for locally absorbed budesonide.

PMID- 11468014
TI  - Usage of the Internet pharmacology resources among European pharmacologists: a
      preliminary investigation.
AB  - The Internet is becoming an ever more important source of information in
      pharmacology and medicine. Little is known, however, about which Internet
      pharmacology resources are actually used by the pharmacologists - and to what
      extent - and how they estimate the Internet information quality and evaluation.
      This pilot study used an anonymous questionnaire, distributed among 250 mostly
      European (220/250) pharmacologists from 30 European countries attending The 2nd
      European Congress of Pharmacology, held in Budapest, Hungary, in 1999. According
      to study results, 93% of all participants use the Internet pharmacology
      resources: 56%, 35% and 9% of them on a daily, weekly and monthly basis,
      respectively. Among 56 pharmacological/medical free online databases offered, the
      general scientific databases were found to greatly prevail (Pub Med 60%,
      Evaluated MEDLINE 37%, Internet Grateful Med 29%, etc.), while drug monographs or
      toxicological databases were less used [e.g. ECDIN, RxList, National Toxicology
      Programme (NTP) < 10%]. Some 80% of the participants estimated the quality of the
      pharmacological information on the Internet as good or very good, while 20%
      thought the quality should be improved. Also, 35% of participants felt the need
      for improvement of the Internet pharmacological information evaluation, which
      should be the goal of pharmacology professional.

PMID- 11468015
TI  - Endoscopic evaluation of the gastrotolerance of short-term antalgic treatment
      with low dose k-diclofenac: a comparison of ibuprofen and aspirin.
AB  - In a short-term gastro-duodenal endoscopic study in 12 healthy volunteers, the
      gastrotoxicity was not different after intake of diclofenac-K 12.5 mg (0.33) or
      ibuprofen 200 mg (0.42, P=0.66) but significantly higher after aspirin 500 mg
      (2.67, P=0.002).

PMID- 11468017
TI  - Biotransformation of xenobiotics by amine oxidases.
AB  - Although the cytochrome P450 (CYP) system ranks first in terms of catalytic
      versatility and the wide range of xenobiotics it detoxifies or activates to
      reactive intermediates, the contribution of amine oxidases and in particular of
      monoamine oxidases (MAOs) to the metabolism of xenobiotics is far from negligible
      but has been largely neglected. In this review on the involvement of amine
      oxidases in the metabolism of xenobiotics, the major characteristics reported for
      the CYP system (protein, reaction, tissue distribution, subcellular localisation,
      substrates, inhibitors, inducers, genetic polymorphism, impact of different
      physiopathological conditions on the activity, turnover) will be compared,
      whenever possible, with the corresponding characteristics of amine oxidases (MAOs
      in particular). The knowledge of the involvement of MAO-A, -B or both in the
      metabolism of a drug allows us to predict interactions with selective or non
      selective MAO inhibitors (e.g. the metabolism of a drug deaminated by both forms
      of MAO is not necessarily inhibited in vivo by a selective MAO-A or -B
      inhibitor). If a drug is metabolized by MAOs, competitive interactions can occur
      with other drugs that are MAO substrates, e.g. with beta-adrenoceptor agonists
      and antagonists, prodrugs of dopamine, serotonin 5-HT1-receptor agonists as well
      as with primaquine, flurazepam and citalopram. Moreover, the knowledge of the
      involvement of MAOs in the metabolism of a drug may suggest possible, although
      not obligatory, interactions with tyramine-containing food or drink, with over
      the counter medicines sold to relieve the symptoms of coughs and colds (generally
      containing the indirectly-acting sympathomimetic amine phenylpropanolamine) or
      with phenylephrine-containing preparations. Finally, biotransformation by amine
      oxidases, as by CYP, does not always lead to detoxication but can produce toxic
      compounds.

PMID- 11468018
TI  - Inflammation, infection and antimicrobial therapy in coronary heart disease-
      where do we currently stand?
AB  - Traditional atherosclerotic risk factors such as hypertension, smoking,
      hyperlipidaemia and diabetes mellitus, account for only about 50% of the clinical
      occurrence of coronary heart disease (CHD). The infectious hypothesis proposes
      that various microorganisms, in particular, Chlamydia pneumoniae, may serve as
      potential etiological factors, linking inflammation and atherosclerosis (or its
      clinical manifestations). Evidence from seroepidemiology, pathology, animal
      models, molecular biology and immunology, and human antibiotic intervention
      studies, collectively have suggested a largely positive association between C.
      pneumoniae infection and CHD. As CHD is a multifactorial disease, it is possible
      that C. pneumoniae may interact with conventional cardiovascular risk factors and
      predispose certain genetically susceptible people to atherosclerotic disease.
      However, the precise nature of a causal or coincidental link between C.
      pneumoniae and CHD remains to be determined. The results of ongoing antibiotic
      intervention studies may help to further clarify the role of infection and
      inflammation in CHD, but until such a role is proven beyond reasonable doubt,
      antimicrobial therapy cannot yet be justified in the treatment or prevention of
      CHD. A current perspective is presented in this review.

PMID- 11468019
TI  - Beta-blocker treatment in heart failure.
AB  - Heart failure treatment has markedly changed during the last few decades, with
      demonstration of benefit of afterload reduction by vasodilator therapy and
      introduction of the concept of the deleterious consequences of the neuro-hormonal
      compensatory stimulation. Blockade of beta-adrenergic receptors, initially contra
      indicated in heart failure, provide a marked reduction of mortality and morbidity
      in combination with diuretics and angiotensin-converting enzyme inhibitors, as
      demonstrated in many clinical trials. We performed a review of all clinical
      trials that compare beta-blockers vs. placebo in chronic heart failure. Beta
      blockers with different pharmacological profiles have been tested, mainly
      metoprolol, bisoprolol, bucindolol and carvedilol. With progressive dose
      increment, tolerance of such treatment was generally good, left ventricular
      function improved, hospitalisations for heart failure were less frequent and
      mortality was reduced. The meta-analysis of the 16 randomised trials, with at
      least one death in each treatment group, provides a 24% relative risk reduction
      for such hospitalisations (95% CI=19%-29%) and 22% reduction for mortality (95%
      CI=16%-28%). Heterogeneity of beta-blocker effect for mortality was found and
      related to the non-significant benefit obtained in the BEST trial with
      bucindolol. When such a trial is excluded, the effect model analysis shows that
      relative risk reduction (beta-blocker induced benefit) is constant whatever the
      severity of the disease. The mechanism of beta-blocker induced benefit remains
      unclear, but is at least partly related to left ventricular function improvement
      and prevention of severe ventricular arrhythmias. In conclusion, beta-blocker
      treatment has become an established therapy for heart failure, in combination
      with diuretics and ACE inhibitors. Complementary informations will be needed to
      clarify the mechanism of benefit and to define the best therapeutic strategy
      according to the individual characteristics of patients with heart failure.

PMID- 11468020
TI  - Effect of endogenous catecholamine on myocardial stunning in a simulated ischemia
      model.
AB  - During ischemia, large amounts of catecholamine are released to the myocardium
      from the sympathetic nerve endings in the heart. It has not been clearly shown
      whether the released catecholamine has detrimental or beneficial effects on
      postischemic myocardial contractile function. The aim of the present study was to
      investigate the effect of endogenous catecholamine released during ischemia on
      myocardial contractile function, using ferret papillary muscles in a stimulated
      ischemia model. Papillary muscles were excised and mounted in organ baths
      containing oxygenated physiological salt solution at 37 degrees C. In order to
      eliminate the effect of endogenous catecholamine, a subset of animals was
      reserpinized for 2 days prior to the experiments. Muscles were stabilized for 1
      h, and stretched to the length at which maximal isometric tension developed.
      Ischemia was simulated by changing the solution to liquid fluorocarbon bubbled
      with 95% N2 and 5% CO2. After 20 min of ischemia, the bathing medium was replaced
      with oxygenated physiological salt solution and developed tension was measured
      for 60 min. Pharmacologic agents with specific effects on myocardial autonomic
      pathways were used to investigate the cellular mechanisms of the observed
      effects. Tension recovery of reserpinized muscles was significantly better than
      control muscles (65.5 +/- 2.8% vs. 54.9 +/- 5.0%, P < 0.01). Exogenously
      administered beta-adrenergic antagonists did not attenuate stunning in control
      muscles; whereas forskolin and carbachol exacerbated stunning. These results
      indicate that catecholamine released during ischemia exacerbates myocardial
      stunning and overrides the effect of clinically relevant concentrations of beta
      adrenergic antagonists, which may limit their ability to protect myocardium from
      acute ischemic insult. The effect of endogenous catecholamine was simulated by
      forskolin, but not attenuated by carbachol, which suggests that changes in the
      contractile apparatus activated by excess cyclic AMP were relevant to the
      mechanical dysfunction that developed.

PMID- 11468021
TI  - Potentiation by nitric oxide synthase inhibitor and calcium channel blocker of
      aspartame-induced antinociception in the mouse formalin test.
AB  - By applying a 12 day regimen of the non-calorific sweetener, aspartame, in
      combination with representative compounds of the calcium channel blocker and
      nitric oxide synthase inhibitor, we tried to investigate using a formalin-test in
      mice the relative role of aspartame on pain and its mechanism of action.
      Verapamil (2, 3.5, 5, 7.5 mg/kg) induced significant (P < 0.01) antinociception
      in both phases of the formalin test. L-Nitro-arginine-methyl-ester (L-NAME) at
      the doses used, induced significant (P < 0.01) antinociception in early phase (1,
      2, 5, 10 mg/kg) and late phase (5, 10 mg/kg). Twelve days of treatment in animals
      by aspartame (0.16% w/v) significantly induced antinociception in both phases of
      the formalin test. Both verapamil (5 mg/kg) and L-NAME (10 mg/kg) significantly
      (P < 0.01) potentiated aspartame-induced antinociception in both phases of
      formalin test. The present findings support the hypothesis that the activation of
      NMDA receptors by aspartame modulates pain-related behaviour via a nitric
      oxide/cGMP/glutamate release cascade. It is concluded that aspartame would be a
      good analgesic agent if it would be used in combination with a calcium channel
      blocker or NOS inhibitor.

PMID- 11468022
TI  - Nitric oxide donor FK409 and 8-bromoguanosine-cyclic monophosphate attenuate
      cardiac contractility assessed by Emax.
AB  - FK409 decomposes and releases nitric oxide (NO) spontaneously when it is
      dissolved in phosphate buffer solution at 37 degrees C. With the use of this NO
      donor, the effect of exogenous NO on cardiac contractility was examined by
      assessing Emax. alpha-chloralose-anaesthetized dogs were instrumented for
      measurements of left ventricular (LV) pressure and volume and coronary blood flow
      (CBF) in the left anterior descending artery (LAD). FK409, 8-bromoguanosine
      cyclic-monophosphate (8-Br-cGMP) and papaverine were infused into the LAD, and
      Emax was determined by transient inferior vena cava occlusion when CBF was
      increased and reached its peak. Neither drug affected heart rate nor LV pressure
      just before the measurement of Emax. FK409 increased CBF and decreased Emax in a
      dose-dependent manner. 8-Br-cGMP also increased CBF and decreased Emax in a dose
      dependent manner. Pretreating with propranolol did not affect the effects of
      FK4098-Br-cGMP on CBF and Emax. Papaverine increased mean CBF but did not affect
      Emax. In conclusion NO attenuates cardiac contractility in vivo, while increasing
      CBF. This effect seems to be mediated by cyclic-guanosine monophosphate, a second
      messenger of NO.

PMID- 11468023
TI  - Effects of CP-060S, a novel cardioprotective drug, in the methacholine-induced
      ECG change model in rats.
AB  - We compared the antianginal effect of CP-060S, a novel cardioprotective drug with
      Na+ and Ca2+ overload-preventing activity as well as Ca2+ channel antagonistic
      activity, with that of diltiazem, in an experimental model of vasospastic angina
      induced by methacholine in anaesthetized rats. Intra-aortic injection of
      methacholine at the coronary ostium provoked the ST-segment elevation of the
      electrocardiogram (ECG), indicating myocardial ischemia. CP-060S (3, 5 and 10
      mg/kg, i.d.) significantly and dose-dependently suppressed the methacholine
      induced ST-elevation, with the duration of action being at least 3 h at the
      highest dose. In addition, CP-060S at 3 mg/kg could inhibit the ST-elevation
      without producing significant changes in blood pressure, heart rate or rate
      pressure product (RPP). In contrast, diltiazem (10 and 30 mg/kg, i.d.)
      significantly decreased the RPP, a significant suppression of the ST-elevation
      could only be achieved at the highest dose and its duration of action was about 2
      h. Similar results were obtained with i.v. administration of the drugs, i.e. CP
      060S given i.v. could inhibit the ST-elevation with less haemodynamic changes
      than diltiazem. In conclusion, CP-060S exerted a more potent and sustained
      protection against myocardial ischemia evoked by methacholine than diltiazem. The
      characteristics of the effects of CP-060S observed here suggest that this drug
      may be a desirable drug for the treatment of vasospastic angina.

PMID- 11468024
TI  - Different types of antagonism by losartan and irbesartan on the effects of
      angiotensin II and its degradation products in rabbit arteries.
AB  - A previous study by our group has demonstrated that the selective AT1-receptor
      antagonist losartan behaves as a noncompetitive antagonist in rabbit isolated
      renal artery (RA). In the present investigation, the influence of losartan and
      irbesartan on the contractile effects of angiotensin II (AII) and its degradation
      products angiotensin III (AIII) and angiotensin IV (AIV) was determined in the
      rabbit isolated RA and femoral artery (FA). The arteries were set up in organ
      chambers and changes in isometric force were recorded. In both rabbit isolated RA
      and FA preparations, AII, AIII and AIV elicited significant contractile responses
      with a similar efficacy. These effects were impaired by the presence of
      functional endothelium in RA preparations but not in FA preparations. In both
      preparations studied, the effects of AII, AIII and AIV were influenced neither by
      the aminopeptidase-A and -M inhibitor amastatin (10 microM), nor by the
      aminopeptidase-B and -M inhibitor bestatin (10 microM). In endothelium-denuded FA
      preparations, preincubation with losartan (3-300 nM) antagonized AII-, AIII- and
      AIV-induced contractions in a competitive manner. However, in endothelium-denuded
      RA preparations, losartan depressed the maximal contractile responses induced by
      AII but not those induced by AIII and AIV. In the same preparations,
      preincubation of another selective AT1-receptor antagonist irbesartan (3-30 nM)
      concentration-dependently shifted AII and AIII curves to the right in an
      insurmountable manner. The reduction of the maximal response of AII is more
      potent when compared to that of AIII (47.7 +/- 1.51% vs. 66.7 +/- 1.88%,
      percentage of the initial maximal response; P < 0.05; n=5). The selective AT2
      receptor antagonist PD123177 (1 microM) did not influence the responses to all
      three peptides in both RA and FA preparations. These heterogeneous antagonistic
      effects of the two AT1-receptor antagonists studied with respect to the
      contractile actions of AII, AIII and AIV suggest the possible existence of
      multiple, functionally relevant AT1-receptor subtypes in rabbit RA preparations.

PMID- 11468025
TI  - Comparison of two methods to obtain a desired first isepamicin peak in intensive
      care patients.
AB  - A randomized multicenter study in intensive care unit (ICU) patients, evaluated
      the capacity of a Bayesian method to obtain an optimal first isepamicin (ISP)
      peak of 80 mg/L in comparison to a fixed loading dose (LD). Patients (n=236) over
      18 years of age were enrolled from 6 September 1997 to 17 July 1999 and randomly
      assigned to received ISP in a calculated dose (CD) or a loading dose (LD) of 25
      mg/kg body weight. The CD was estimated using a specific population model with
      Bayesian methodology implemented in the PKS program (Abbott PKS, Abbott
      Diagnostics, Rungis, France). The data required included age, body weight,
      height, gender and serum creatinine. ISP disposition is described by a one
      compartment model. Blood samples were drawn 1 and 24 h after the start of
      infusion for fluorescence polarization immunoassay measurement of serum ISP
      concentrations. The predictive performance was assessed by computing bias and
      precision. Peak concentrations were significantly higher in CD group than the LD
      group (84.2 +/- 28.6 vs. 74.7 +/- 24.1 mg/L, respectively; P=0.008), but trough
      levels were comparable. The optimal ISP peak was attained by a significantly
      higher percentage of CD patients (P=0.018), and by significantly more CD patients
      on mechanical ventilation (P=0.025), and with simplified acute physiological
      scores (SAPS) > 35 (P=0.002). Pharmacokinetic parameters were similar for the two
      groups with large interindividual variations. Mean (+/- SD) volume of
      distribution of ventilated patients (72%) was significantly higher than of
      nonventilated patients (23.31 +/- 7.35 vs. 20.60 +/- 6.30 L, respectively;
      P=0.001). No relationship was found between the volume of distribution and SAPS.
      Total clearance was significantly correlated with estimated CLCR (creatinine
      clearance) (P=0.0001). Precision (RMSE) is better for CD than for LD strategy,
      respectively 27.96 and 28.66 mg/L. The Bayesian method was significantly more
      accurate and performed particularly well in ventilated patients and patients with
      high SAPS, compare to an LD of 25 mg/kg to obtain a first ISP peak of 80 mg/L in
      ICU patients. Therefore, a fixed dose of 28.5 mg/kg would be also adequate to
      reach a peak of 80 mg/L.

PMID- 11468026
TI  - Blood pressure and vascular reactivity to endothelin-1, phenylephrine, serotonin,
      KCl and acetylcholine following chronic alcohol consumption in vitro.
AB  - Ethanol has been reported to cause hypertension, the mechanism of which is
      unknown. Therefore, the effect of chronic ethanol consumption on vascular
      responsiveness and blood pressure was investigated. Systolic blood pressure was
      recorded weekly by tail-cuff method. Aortic rings from rats fed chow ad libitum
      or pair-fed liquid diets containing either ethanol (7.2% v/v) or isocaloric
      carbohydrate for 4 weeks were placed in organ chambers for isometric tension
      measurement. There was a mild but significant elevation of the systolic blood
      pressure in the alcohol-fed rats by week 1 compared to baseline measurements and
      this remained higher. No significant changes in reactivity of rat isolated aortas
      to phenylephrine, serotonin, endothelin-1 (ET-1) and KCl were seen in chronic
      ethanol consumption. In addition, the sensitivity (i.e. pD2) of alcohol-fed
      aortic rings to the vasoconstrictors was also unchanged compared to controls.
      Chronic ethanol consumption, however, increased relaxation to acetylcholine with
      increased pD2 values, but did not alter relaxation to sodium nitroprusside, a
      cyclic guanosine monophosphate (cGMP)-dependent direct smooth muscle dilator. The
      results indicate that chronic ethanol consumption significantly potentiates
      endothelium-dependent relaxations in aortic rings, probably through interference
      with the production and/or the release of nitric oxide (NO) or adaptive
      alterations in muscarinic receptors on the endothelial cells, and that increased
      vascular responsiveness to several vasoconstrictors is not a mechanism
      responsible for the blood pressure elevation in the chronic alcohol consumption
      in rats.

PMID- 11468027
TI  - Role of K+ -channels in homotaurine-induced analgesia.
AB  - In previous articles, antinociceptive activity for homotaurine has been
      demonstrated to be mediated by opioid, GABAergic and cholinergic mechanisms.
      GABAB-agonists affect K+-channels and it is known that K+-channels modulate
      specific activation of opioid receptors. In this study, we examined the
      involvement of K+-channels in the antinociceptive activity of homotaurine (22-445
      mg/kg). Antinociceptive response was obtained after icv pretreatment with the
      channel specific blockers 4-aminopyridine (voltage-dependent channels),
      tetraethylammonium (Ca++ and voltage-dependent) and gliquidone (ATP-dependent).
      The nociceptive tests performed were acetic acid induced abdominal constriction
      (mice) and tail flick (rats) tests. Acetic acid responses to homotaurine were
      inhibited by tetraethylammonium (5 microg) and gliquidone (16 microg). Tail flick
      response to homotaurine was inhibited by tetraethylammonium (50 microg),
      gliquidone (40 and 80 microg) and 4-aminopyridine (25 and 250 ng). These results
      suggest an involvement of the three types of K+-channels in antinociception by
      homotaurine, depending on specific homotaurine and blocker doses. At a spinal
      level, they appear to be involved together with GABAB and opioid mechanisms.
      Peripherally, only tetraethylammonium channels would be substantially activated
      during homotaurine antinociceptive effect.

PMID- 11468028
TI  - Effect of centrally administered prolactin on gastric and duodenal ulcers in
      rats.
AB  - The effect of centrally administered prolactin on gastric acid secretion and
      experimentally-induced gastric and duodenal ulcers was studied. The acute gastric
      ulcer models used were pylorus ligation, indomethacin-induced and ethanol-induced
      gastric ulcers. Chronic gastric ulcers were induced using acetic acid and
      duodenal ulcers by cysteamine hydrochloride. In pylorus ligated rats, prolactin
      (1 microg/kg icv) produced 45% increase in gastric content volume, significant
      increase in free acidity (P < 0.001), total acidity (P < 0.001) and ulcer index
      (P < 0.001). It did not show any significant effect on ethanol-induced and
      indomethacin-induced gastric ulcers. Prolactin increased the ulcer index (P <
      0.001) and ulcer score (P < 0.05) in acetic acid-induced chronic gastric ulcers.
      It also increased ulcer area (P < 0.05) in cysteamine-induced duodenal ulcers.
      Therefore, the proulcerogenic activity of prolactin was due to its gastric
      hypersecretory effect.

PMID- 11468029
TI  - The role of the interaction between endogenous opioids and nitric oxide in the
      pathophysiology of ethanol-induced gastric damage in cholestatic rats.
AB  - Interaction between endogenous opioids and nitric oxide (NO) has been shown in
      different biological models and pharmacological evidence suggest that opioids can
      induce NO release in endothelium as well as in neural cells. Cholestasis is
      associated with NO overproduction. The reason for increased NO synthesis is not
      clearly known but it can potentiate development of gastric mucosal damage in
      cholestatic subjects. Based on increased plasma levels of endogenous opioids and
      existence of NO overproduction in cholestasis, the present experiments were
      performed to investigate the role of interaction between endogenous opioids and
      NO in generation of ethanol-induced gastric damage in cholestatic rats.
      Cholestasis was induced by surgical ligation of bile duct and sham-operated rats
      served as controls. The animals received either 20 mg/kg of naltrexone or saline
      for 6 days and then were fasted and received L-arginine (200 mg/kg), NG-nitro-L
      arginine methylester (L-NAME; 2, 5 and 10 mg/kg) or saline. The ethanol-induced
      gastric mucosal damage was significantly more severe in cholestatic rats than in
      sham-operated animals (115 +/- 12 mm2 vs. 72 +/- 11 mm2, P < 0.05). L-NAME
      significantly enhanced the development of gastric mucosal lesions in sham
      operated rats. But in cholestatic animals, L-NAME decreased and L-arginine
      enhanced the severity of gastric damage. Pretreatment of animals with naltrexone
      decreased severity of gastric mucosal damage in cholestatic rats. Concurrent
      administration of naltrexone with L-arginine was protective against ethanol
      induced gastric damage in both normal and cholestatic groups. Administration of
      naltrexone with L-NAME had the same effect in cholestatic and control rats and
      increased severity of gastric damage. Plasma levels of NO2- + NO3- were
      significantly higher in cholestatic rats than control animals (72 +/- 6 microM
      vs. 39 +/- 3 microM, P < 0.05). Pretreatment of animals with naltrexone
      significantly reduced plasma levels of NO2- + NO3- in cholestatic animals, but
      not in control rats (33 +/- 6 microM vs. 32 +/- 4 microM). The protective effect
      of L-NAME against gastric damage in cholestatic rats can be explained by
      inhibition of NO overproduction and it seems that interaction between opioids and
      NO may have an important role in generation of NO overproduction and gastric
      complications in cholestatic rats.

PMID- 11468030
TI  - A nonpeptide vasopressin V(1a) receptor antagonist, SR 49059, does not prevent
      cisplatin-induced emesis in piglets.
AB  - We determined the pharmacological and the antiemetic properties of SR 49059, a
      selective nonpeptide V(1a) receptor antagonist, on cisplatin-induced emesis in
      the piglet. Firstly, we clearly demonstrate that SR 49059 is a potent V(1a)
      receptor antagonist in vitro and in vivo in the piglet. In binding studies, [3H]
      SR 49059 exhibited high affinity for V(1a) receptors in piglet liver membranes
      (K(d) of 0.76 +/- 0.12 nM and B(max) of 138 +/- 22 fmol/mg prot.). In vivo, in
      decerebrate piglets, SR 49059 (1 mg/kg iv) antagonized AVP (500 ng/kg iv)-induced
      hypertension for at least 150 min and also blocked, for at least 270 min at 3
      mg/kg iv, the pressor responses to exogenous LVP. After single and repeated iv or
      icv administration, we studied the antiemetic properties of SR 49059 on cisplatin
      induced emesis in piglets. Animals receiving an emetic dose of cisplatin (5.5
      mg/kg, iv) were observed continuously for 60 h. Piglets acting as controls were
      iv administered with vehicle 15 min prior to cisplatin infusion (T0(-15min)),
      while experimental animals received a single iv administration of SR 49059 at the
      dose of 1 or 3 mg/kg. In additional piglets, we administered SR 49059 (3 mg/kg)
      every 12 h from T0(-15min) to T48(-15min) (cumulative dose, 15 mg/kg). Another
      set of animals - observed only during the acute phase - was administered with SR
      49059 (10 mg/kg) every 3 h from T0(-15min) to T15(-15min) (cumulative dose, 60
      mg/kg). Lastly, 10 piglets were given a bilateral icv injection of SR 49059 (500
      microg and 1500 microg/side) 1 h prior to cisplatin infusion. In all groups
      treated with SR 49059, the latency of the first emetic episode and the incidence
      of vomiting during the acute, the delayed and the cumulative phases remained
      statistically similar to that observed in controls, suggesting that V(1a)
      receptors are not involved in the onset and completion of nausea and vomiting.

PMID- 11468031
TI  - Diazepam enhances etoposide-induced cytotoxicity in U-87 MG human glioma cell
      line.
AB  - Various approaches might be employed in an effort to increase efficacy of the
      chemotherapeutic treatment of cancer. Recently, various modulators of anticancer
      therapy effectiveness have been studied. Antiproliferative effects of peripheral
      benzodiazepine receptor (PBR) ligands might be exploited to enhance cytotoxic
      effect of a chemotherapeutic drug towards cancer cells. In this work, we sought
      to enhance cytotoxic effect of etoposide (VP-16) by a PBR ligand, diazepam (DZ)
      in U-87 MG human glioma cells. Cytotoxicity of VP-16, DZ and their combinations
      was assessed by using the microculture MTT assay. Cell survival, effective
      concentrations (EC) and the onset of cytotoxic effect were determined. After 72 h
      of cultivation, survival of U-87 MG cells was reduced to 57 +/- 7% in the
      presence of VP-16 at 12.5 microg/mL alone, whereas DZ at 10-4 mol/L alone caused
      28 +/- 6% reduction in cell survival. Coincubation of VP-16 at 12.5 microg/mL
      with DZ at 10-4 mol/L led to a further decrease in cell survival to 45 +/- 6%.
      Furthermore, DZ at 10-4 mol/L significantly decreased effective concentrations,
      EC10, EC30 and EC50, of VP-16 and the dose-response curves were shifted to the
      left. Addition of DZ at 10-4 mol/L to VP-16 also facilitated the onset of its
      cytotoxic effect. The same decrease in survival was thus achieved approximately
      30 h earlier in comparison with VP-16 alone. However, DZ at 10-9 mol/L failed
      both to exert any effect on glioma cells survival and enhance cytotoxic effect of
      VP-16. DZ at 10-4 mol/L was capable of both reducing U-87 MG glioma cells
      survival when applied alone and also enhancing the cytotoxic effect of VP-16. No
      such observation was made for the lower concentrations of DZ. Potential
      implementation of diazepam in the antiglioma/anticancer armamentarium awaits
      further experimentation but phase I and phase II clinical trials could be
      suggested.

PMID- 11468032
TI  - A double blind parallel group placebo controlled comparison of sedative and
      mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].
AB  - This paper describes the psychomotor and mnesic effects of single oral doses of
      etifoxine (50 and 100 mg) and lorazepam (2 mg) in healthy subjects. Forty-eight
      healthy subjects were included in this randomized double blind, placebo
      controlled parallel group study [corrected]. The effects of drugs were assessed
      by using a battery of subjective and objective tests that explored mood and
      vigilance (Visual Analog Scale), attention (Barrage test), psychomotor
      performance (Choice Reaction Time) and memory (digit span, immediate and delayed
      free recall of a word list). Whereas vigilance, psychomotor performance and free
      recall were significantly impaired by lorazepam, neither dosage of etifoxine (50
      and 100 mg) produced such effects. These results suggest that 50 and 100 mg
      single dose of etifoxine do not induce amnesia and sedation as compared to
      lorazepam.

PMID- 11468033
TI  - Pharmacokinetics of alizapride in children receiving chemotherapy for solid
      tumour.
AB  - The purpose of the present study was to determine the pharmacokinetics of
      alizapride to optimize its use in children aged 1 month to 15 years old who were
      receiving chemotherapy. Seventeen children were given a single 4 mg/kg alizapride
      infusion prior to the administration of cytostatic drugs. Blood and urine samples
      were collected within 10 h after onset of the infusion. Kinetic parameters were
      calculated and showed a decrease in plasma clearance expressed per unit of body
      weight with age. The current data suggest that dosage expressed per unit of body
      weight should be higher in children than in adults and higher in infants than in
      children.

PMID- 11468034
TI  - Are there early features of autism in infants and preschool children?
AB  - Autism is characterized by impairments in three areas: (i) reciprocal social
      interaction; (ii) communication; and (iii) repetitive and stereotyped patterns of
      interest and behaviour. Despite the finding that parents notice abnormalities and
      problems with their child's development at a very early age, research shows that
      diagnoses are often made at an age beyond that recommended for the commencement
      of early intervention. This paper reviews the range of studies that have sought
      to elucidate the early features of autism in young, preschool children.
      Impairments in the capacity for reciprocal social interaction involving
      preverbal, verbal and non-verbal communication, and play and symbolic behaviour
      are the key features indicative of autism in infants and preschool children.

PMID- 11468035
TI  - Child injury morbidity in New Zealand, 1987-1996.
AB  - OBJECTIVES: New Zealand is one of a small number of countries that has a national
      hospital discharge database. The aim of this study was to use these data to
      provide an epidemiological description of child injury morbidity and to discuss
      options for prevention. METHODOLOGY: Using national data, all public hospital
      admissions for the fiscal year 1995/6 were identified and grouped according to
      cause. This allowed identification of all children (0-14 years) hospitalized for
      injury in the period 1987-1996. Causes of injury, diagnoses and injury severity
      were examined in four age groups. RESULTS: Injury was the second leading cause of
      public hospital admissions. Children were hospitalized with injury at the rate of
      1333 per 100 000 person-years. The victims were predominantly male (61%). In all
      age groups, falls were the leading cause of morbidity. 'Striking events', motor
      vehicle traffic crashes and poisoning were also major contributors to the child
      injury toll. The commonest injury diagnosis was a fracture of the upper limb
      (25%), followed by intracranial injury (18%). CONCLUSIONS: The leading causes of
      injury morbidity were noted to differ from previously reported leading causes of
      injury mortality. Review of the data in light of research literature suggests the
      need for policy changes to make alternatives to motor vehicle transportation
      safer and to encourage increased use of child restraints in order to reduce road
      traffic trauma. Legislation requiring child-resistant packaging for all toxic
      medications and household products is necessary to reduce rates of child
      poisoning. Further research is required on policies concerning playground
      equipment heights and surfacing requirements, and on interventions for hot water
      scalds.

PMID- 11468036
TI  - Paediatric walk-out patients: characteristics and outcomes.
AB  - OBJECTIVE: To investigate the characteristics and outcomes of patients who walked
      out from a tertiary children's hospital emergency department (ED) without seeing
      a medical officer. METHODS: A prospective study of patients who walked-out from
      the ED of a children's hospital, without seeing a medical officer. Information
      collected at triage included demographics, presenting problems, time of arrival,
      time of departure and reason for leaving. Charts were reviewed and those at high
      risk of serious illness or adverse outcome were contacted by telephone within 24
      h. Further information collected during follow up included outcome, such as
      adverse events and admission to hospital. Data were analysed by comparing the
      walk-out and non-walk-out groups with regard to demographic variables, presenting
      problems and outcomes. RESULTS: Over a 29 week period, 1037 (5.5%) patients
      walked out from the ED of the hospital without seeing a medical officer.
      Comparisons between the walk-out and non-walk-out patients indicated no
      differences in terms of demographics. However, significant differences were found
      between the triage categories, presenting problems and arrival time. Of these,
      829 (79.9%) were followed up by telephone. This revealed the predominant
      presenting problem was non-urgent and infectious in nature and no adverse events
      occurred. The admission rate for walk-out patients (1.5%) was significantly lower
      in comparison with the non-walk-out group (6.9%; odds ratio 0.2; 95% confidence
      interval 0.1-0.3). Walk-out patients who were eventually hospitalized had a
      shorter mean length of stay than non-walk-out patients (20.4 vs 34.8 h,
      respectively; t = 17.78, P < 0.0001). CONCLUSIONS: Medical resources are limited
      and, therefore, some extended waiting in the ED is necessary. Paediatric patients
      who walk-out of the ED without seeing a medical officer have simple illnesses
      that resolve without medical intervention or adverse events.

PMID- 11468037
TI  - Epidemiology of Munchausen syndrome by proxy in New Zealand.
AB  - OBJECTIVE: To determine the epidemiology of Munchausen syndrome by proxy (MSBP)
      in New Zealand and describe the effects of this condition on children and their
      paediatricians. METHODOLOGY: A mail-out survey was sent to all paediatricians in
      New Zealand in 1999. Paediatricians were asked to identify all cases of MSBP, non
      accidental poisoning or non-accidental suffocation diagnosed or suspected in
      children less than 16 years of age that had been seen in the past 12 months.
      Those paediatricians who identified a case were then interviewed by telephone to
      ensure that identified cases were new cases and that they were unique. RESULTS:
      Responses were obtained from 148 (95%) of 156 practising paediatricians in New
      Zealand. Eighteen unique cases of MSBP were identified where the diagnosis had
      been made in the preceding 12 months. The incidence rate for MSBP in children
      aged less than 16 years was 2.0/100 000 children. Eleven (61%) of the 18 cases
      were referred to child protection agencies or the police. The mean time taken to
      diagnosis from initial presentation was 7 months in the cases referred to child
      protection agencies and 23 months in cases not referred. The median age at
      diagnosis was 2.7 years. The mother was the suspected perpetrator in all cases.
      Most children (72%) presented with multiple symptoms. Over half (55%) had an
      underlying chronic illness. The morbidity for the child in the majority of cases
      was not severe, and in nine (50%) cases it was noted that following diagnosis
      there was improvement or resolution of symptoms. Ten (56%) of the 18
      paediatricians involved with cases reported experiencing considerable stress.
      CONCLUSIONS: The annual incidence in New Zealand of MSBP in children under 16
      years is higher than that reported from other countries. Chronic illness is often
      associated with this condition. The morbidity for the majority of children was
      not severe and often improved with diagnosis. Paediatricians reported stress and
      difficulty in association with caring for children with this syndrome of child
      abuse.

PMID- 11468038
TI  - Risk of hepatitis C virus infection in multiply transfused premature neonates.
AB  - BACKGROUND: Reports from around the world indicate that multiply transfused
      patients are at increased risk of hepatitis C virus (HCV) infection, with
      reported rates of between 4% and 44%. Such reports are mostly of haematological
      and renal patients. As recipients of blood products in the newborn period,
      premature infants share this risk, but there is little information regarding
      their risk. AIM: To assess the risk of HCV infection in children who, as
      premature neonates, received multiple blood products prior to the introduction of
      screening of donated blood for HCV. METHODS: Premature infants born between
      January 1985 and January 1990 who had attended our high-risk follow-up clinic
      were selected on the basis of the number of transfusions of blood, platelets or
      fresh frozen plasma they received in the newborn period. Ethical approval to
      offer HCV testing to parents was obtained from the Central Sydney Area Health
      Service Ethics Review Committee. Parents of infants who received three or more
      transfusions were then contacted by mail with the approved letter explaining the
      study, and offered HCV testing. Detection of anti-HCV antibodies was undertaken
      using second, and later third generation enzyme immunoassay kits. Samples which
      were found to be 'indeterminate' were tested using a Wellcozyme HCV western blot
      assay (Murex Diagnostics Ltd, Datford, UK). Hepatitis C virus-ribonucleic acid
      (RNA) was detected using an 'in-house' polymerase chain reaction (PCR) assay.
      Alanine transaminase (ALT) was also measured, with values above 55 U/L considered
      abnormal. RESULTS: Consent was obtained for 45 children (25 males, 20 females).
      The mean (+/- SEM) gestational age and weight of the children at birth was 26.7
      +/- 0.2 weeks and 938 +/- 27 g, respectively. The children received 198
      transfusions of blood products, an average of 4.4 U per child. All of the infants
      except for one were negative for anti-HCV antibodies. One infant was
      'indeterminate' (low positive on third generation test but negative on second
      generation test), but proved negative subsequently on both western blot and PCR
      testing. HCV-RNA was not detected in any of the infants on PCR testing. All of
      the samples had normal ALT values, the mean being 16 U/L (range 8-52).
      CONCLUSION: None of the children consenting to this study had evidence of current
      HCV infection. Because of the sample size, we were not able to estimate the true
      risk of infection from this study, except that the upper limit for the risk is
      about 1/200 per transfused blood sample.

PMID- 11468039
TI  - Growth and nutrition of Chinese vegetarian children in Hong Kong.
AB  - OBJECTIVE: The study investigated the nutritional status of Chinese lacto-ovo
      vegetarian children aged 4-14 years. METHODOLOGY: Dietary intake over 7 days was
      assessed using a computer program, previously used for a local population-based
      dietary survey. Anthropometric measurements were made and fasting venous blood
      was examined for serum lipids, haematological data, iron, vitamin B12 and folate
      status. Bone mineral density (BMD) of the spine (L2 - L4) was measured as a
      reflection of calcium status. RESULTS: Fifty-one lacto-ovo-vegetarians aged 4-14
      years were investigated. The mean +/- standard deviation (SD) daily energy intake
      was 1600 +/- 425 kcal. The mean (+/- SD) daily protein intake was 1.6 +/- 0.6
      g/kg bodyweight which met the United States recommended dietary allowance.
      Compared to that of the local omnivore diet, the vegetarian diet was closer to
      the recommended healthy diet with lower fat (20-23%), more fibre (5.8-8.7 g/day)
      and better polyunsaturated to saturated fatty acid ratio (1.0-1.1). Growth and
      BMD of the vegetarian children were comparable to the general omnivore
      population. Two children had iron deficiency and two children had anaemia. The
      calcium status, as reflected by the BMD, was not impaired. Serum folate and
      vitamin B12 were within the normal range. Six (25%) boys and four (15%) girls
      were obese. Three boys had hyperlipidaemia. CONCLUSIONS: A Hong Kong Chinese
      vegetarian diet appears healthy, providing adequate iron and vitamin B12
      nutrition, but the prevalence of obesity was high.

PMID- 11468040
TI  - Factors associated with breastfeeding at discharge and duration of breastfeeding.
AB  - OBJECTIVE: To identify determinants of the initiation and duration of
      breastfeeding amongst Australian women. METHODS: A prospective cohort study of
      556 women in Perth, Western Australia and 503 women from the Darling Downs area,
      Queensland, Australia. RESULTS: Breastfeeding at discharge was most strongly
      associated with perceived paternal support of breastfeeding with an adjusted odds
      ratio of 9.13 (95% CI 4.83-17.26), using multivariate logistic regression
      analysis. Duration of breastfeeding was most strongly associated with the length
      of time a mother intended to breastfeed with an adjusted relative risk of 4.18
      (95% CI 2.81-6.22) for > or = 4 months relative to < 4 months. CONCLUSIONS:
      Interventions which aim to increase the length of time a woman intends to
      breastfeed, and which highlight the role of the father in successful
      breastfeeding, are recommended to help achieve recommended targets for
      breastfeeding initiation and duration.

PMID- 11468041
TI  - Childhood poisoning: access and prevention.
AB  - OBJECTIVES: To investigate the circumstances and means of access to six poisoning
      agents by children under 5 years of age and to make recommendations for
      countermeasures and strategies for implementation. METHODOLOGY: A case series
      study of access to six poisoning agents was conducted. Cases were identified
      prospectively through a poisons information centre and hospital emergency
      departments. Interviews were conducted with 523 parents and caregivers using a
      structured questionnaire. RESULTS: The majority of children (94.1%) accessed the
      agent in their own home or another home and, in 38% of cases (excluding mistakes
      in administration), the parent or caregiver was present in the immediate area at
      the time of the incident. In cases in which the child was alone in the room,
      caregivers were frequently involved in household duties (51%), with only 10%
      undertaking leisure activities and 8% on the telephone. The span of unsupervised
      time reported was 5 min or less in 79.5% of these cases. The means of access was
      generally during periods of use of the agent (75.3%), including just purchased,
      rather than when agents were in their usual storage place. CONCLUSIONS: There is
      little scope for improved supervision as a major intervention. Design and
      regulatory changes such as local safe storage for bench tops and while
      travelling, improved labelling and packaging, improved child-resistant packaging
      and its more general application are required. These and agent-specific
      interventions, including child-resistant bait stations for rodenticides and well
      covers for vaporizers, are more likely to prevent poisoning. The recent
      identification of childhood poisoning prevention as a national priority may lead
      to coordinated action to implement these and other preventive measures.

PMID- 11468042
TI  - Coordinated outpatient care of the narcotic-dependent infant.
AB  - OBJECTIVE: Concern regarding parental capacity to manage their infant's drug
      withdrawal traditionally leads to prolonged hospitalization for both mother and
      infant. This study examines the impact of a multidisciplinary follow-up clinic
      for infants discharged home on morphine. METHODOLOGY: Records of full-term
      infants born to mothers with narcotic dependency were reviewed retrospectively.
      Two periods were compared: 1995-1997 (period A) and 1998 to September 1999 with
      clinic established (period B). RESULTS: Twenty-five and 26 mothers were
      identified in periods A and B, respectively. Almost half had fewer than four
      antenatal clinic visits and most were on methadone with other substance usage.
      Despite higher maternal methadone doses (mean 48.5 vs 89.5 mg/day, P = 0.009) and
      withdrawal rates, the mean length of stay was significantly shorter for period B
      mothers (7.8 +/- 4.8 vs 5.4 +/- 3.3 days, P = 0.01) and babies (14.8 +/- 9.7 vs
      8.7 +/- 7.2, P = 0.01). Median duration of morphine treatment was significantly
      shorter in period A (17 vs 60 days, P = 0.0001) when only four babies were
      discharged on morphine. In contrast, 18 treated period B babies were discharged
      on morphine. No families were lost to follow up. Compliance with clinic
      attendance was 92%. CONCLUSIONS: Hospital stay was reduced with establishment of
      the clinic. The shorter treatment duration before establishment of the clinic
      could have been related to a lesser abstinence severity or a perceived need of a
      more rapid weaning prior to discharge. Further studies are needed to assess the
      impact of this model of care on the health outcome of the narcotic-dependent
      mother and infant unit.

PMID- 11468043
TI  - Perception of fear, distress and pain by parents of children undergoing a
      micturating cystourethrogram: a prospective study.
AB  - OBJECTIVES: To investigate whether parents' expectations of their child's fear,
      distress or pain during a micturating cystourethrogram (MCU) are realized.
      METHODOLOGY: Prospective study in which parents were asked to fill out two
      questionnaires using a visual analogue scale, one before (pre) and the other
      after the MCU procedure (post), was conducted at a tertiary level paediatric
      hospital in Sydney, Australia. The questionnaires were designed to compare the
      parents' anticipated and experienced anxiety about their child's procedure and
      their perception of fear, distress and pain in their child during and after the
      procedure. The parents' satisfaction with information provided to them on the
      procedure was also recorded. Twenty-five parents participated in the study.
      RESULTS: There were significant differences between anticipated and experienced
      parental anxiety. Parents' reporting of fear, distress and pain in their child
      during the MCU and after the procedure was lower than they had anticipated. There
      was a significant correlation between the parents' anxiety and their perception
      of severity of their child's fear (r = 0.52, P = 0.009), distress (r = 0.48, P =
      0.017) and pain (r = 0.50, P = 0.01) during the procedure, but less so with the
      child's distress after the procedure (r = 0.39, P = 0.059). The parents were
      satisfied with the information given to them regarding the MCU procedure.
      CONCLUSIONS: Parents' perception of their child's fear, distress and pain during
      the MCU, as well as distress following the MCU, was not as severe as they had
      anticipated. Parental anxiety is an important factor in the perception of fear,
      distress and pain in children during and after the procedure.

PMID- 11468044
TI  - Outcome following surgical closure of secundum atrial septal defect.
AB  - OBJECTIVE: To assess the current outcome of surgical closure of secundum atrial
      septal defects (ASD) in an Australian paediatric population. METHODOLOGY: A
      retrospective chart review of 87 children, aged 2 months to 15 years, was
      performed for surgery between August 1995 and March 1999. RESULTS: There were no
      deaths in the patients studied. Approximately one in four patients (24.1%)
      experienced complications requiring further management. Complication rates were
      similar to those published previously. However, one in nine patients (11.5%)
      required surgical drainage of a pericardial effusion. A total of five of 87
      (5.7%) patients developed post-pericardiotomy syndrome (PPS), of whom four
      required pericardiocentesis. The risk for developing a pericardial effusion
      requiring drainage or PPS was more than twice in children older than 5 years of
      age at the time of surgery compared to those aged under 5 years, although there
      was an insufficient number of subjects in the study to prove this statistically
      (Odds ratio 2.31). CONCLUSIONS: Most patients have an uncomplicated postoperative
      course following surgical closure of secundum ASD. However, a significant
      minority (24.1%) do develop complications requiring further management and have a
      correspondingly longer period of hospitalization. Patients older than 5 years of
      age were identified as being potentially at greater risk for the development of
      PPS or a pericardial effusion requiring drainage. Further research needs to be
      performed to clarify this.

PMID- 11468045
TI  - Conductive hearing loss in preterm infants with bronchopulmonary dysplasia.
AB  - OBJECTIVE: To determine the risk of conductive hearing loss in preterm infants
      with bronchopulmonary dysplasia (BPD) and preterm controls. METHODOLOGY: The
      study population consisted of 78 infants with BPD of 26-33 weeks gestation and 78
      controls of similar gestational age matched for broad-based birthweight
      categories. An auditory brainstem response (ABR) audiology was performed shortly
      before hospital discharge. Visual reinforcement orientation audiometry (VROA) and
      impedance audiometry were performed at 8-12 months corrected for prematurity.
      Infants with persistent audiological abnormalities were referred for evaluation
      to paediatric ENT surgeons. RESULTS: Infants with BPD had a significantly higher
      rate of ABR abnormalities (BPD: 22%, controls: 9%; P = 0.028). On VROA and
      impedance audiometry, the infants with BPD also had a higher rate of persistent
      abnormalities. Following ENT assessment, 22.1% of infants with BPD and 7.7% of
      controls had persistent conductive dysfunction requiring myringotomy and grommet
      tube insertion (P = 0.03). Most of these infants had normal ABR audiometry at
      hospital discharge. CONCLUSIONS: Preterm infants with BPD are at high risk of
      persistent conductive hearing loss late in the first year of life compared to
      controls. An ABR audiology conducted at the time of hospital discharge does not
      predict accurately later conductive hearing problems. Infants with BPD should
      have routine audiological evaluation toward the end of the first year of life.

PMID- 11468046
TI  - Continuous intrathecal baclofen infusion for children with cerebral palsy: a
      pilot study.
AB  - OBJECTIVES: To determine whether continuous intrathecal baclofen infusion (CIBI)
      would decrease spasticity and improve function in children with spastic cerebral
      palsy. DESIGN: Prospective study with measurement of changes from baseline
      assessed at regular intervals for 6 months following the intervention. PATIENTS:
      Two subjects aged 8 and 9 years with cerebral palsy. Inclusion criteria included
      severe spasticity and age greater than 4 years. STUDY CENTRE: Department of
      Rehabilitation, The Children's Hospital at Westmead, Westmead, New South Wales,
      Australia. RESULTS: Both subjects had clinically significant reductions in lower
      limb spasticity from a single intrathecal dose of baclofen (screening procedure),
      and had intrathecal pumps implanted. An intensive physical therapy programme was
      provided for both subjects in the 1-3-month period after commencing CIBI, in
      order to maximize functional gains. Modified Ashworth Scale scores remained
      reduced during the 6-month study period. There was a clinically significant
      increase in upper limb function for Subject 1. Gross Motor Function Measure
      scores decreased from 22% to 19% for Subject 1, and increased from 6% to 10% for
      Subject 2 over the study period. Paediatric Evaluation of Disability Inventory
      scores for Subject 1 showed a reduction in the level of caregiver assistance
      required, while Subject 2 showed significant improvement in the functional
      mobility domain. The major changes noted in the parent questionnaires were
      reduction in tone, increased range of motion and reduced time taken helping with
      activities of daily living such as toilet and dressing. No significant side
      effect was seen after the screening procedure or after continuous intrathecal
      infusion. Both subjects' parents felt their child was improved following the
      intervention. CONCLUSIONS: Children with spastic cerebral palsy can have their
      spasticity effectively reduced with CIBI. In this study of two children, the
      clinical improvements were encouraging, and it is proposed that CIBI may be of
      benefit to those patients whose level of spasticity severely interferes with
      function. Further studies using multidimensional assessment approaches, with
      larger numbers of children, are warranted.

PMID- 11468047
TI  - Use of a behavioural programme in the first 3 months to prevent infant crying and
      sleeping problems.
AB  - OBJECTIVE: To assess the effectiveness of a behavioural programme introduced in
      the first 3 months of age in preventing infant crying and sleeping problems. Two
      issues were addressed: (i) which elements of the behavioural programme would
      parents implement; and (ii) whether the behavioural programme was more effective
      in reducing infant crying and encouraging night-time sleeping than an educational
      intervention or the routine services. METHODOLOGY: Mothers and newborns were
      assigned at random to the behavioural programme (n = 205), educational
      intervention (n = 202), or control (n = 203) group. Behaviour diaries kept before
      randomization and at 3, 6, 9 and 12 weeks of age were used to measure
      implementation of the interventions and infant behaviour, including crying and
      sleeping. Crying and sleeping problems were followed up using questionnaire
      measures at 9 months of age. RESULTS: The educational intervention did not change
      parental care behaviour. One element of the behavioural programme, a focal feed
      between 10 PM and midnight, was not implemented. A second element, stretching of
      interfeed intervals after 3 weeks of age, was implemented initially, but not
      maintained at older ages. The third element, which asked parents to emphasise day
      and night differences in the environment, and to settle their babies in the cot
      and minimise interaction at night, was carried out by more parents in the
      behavioural group than in the other groups. This led to an increase of around 10%
      in the number of babies who slept for 5 or more hours at night (a definition of
      sleeping through the night) at 12 weeks of age. Fewer behavioural programme
      parents sought help for crying and sleeping problems between 3 and 9 months of
      age. CONCLUSION: The behavioural programme produced a modest increase in the
      number of infants who slept through the night by 12 weeks of age. The results are
      discussed in relation to other findings, which bear on the programme's adoption
      for routine health-care policy and practice.

PMID- 11468048
TI  - Serum sickness-like reaction to cefaclor.

PMID- 11468049
TI  - Girl with dopa-responsive dystonia.

PMID- 11468050
TI  - Delayed presentation of an ingested foreign body causing gastric perforation.
AB  - Ingested foreign bodies may lead to perforation of the gastrointestinal tract. We
      present a case of a 14-month-old boy who presented with an unusual abdominal mass
      secondary to ingesting a foreign body 4 months previously. Abdominal computerized
      tomography scan was valuable in making this diagnosis.

PMID- 11468051
TI  - Indomethacin treatment of infantile cortical periostosis in twins.
AB  - Twin girls presented with infantile cortical periostosis (Caffey's disease) at 2
      and 3 weeks of age, respectively. This disorder initially involved their upper
      and lower limbs and resulted in fever, irritability and tenderness. X-rays showed
      extensive periosteal new bone formation. Multiple relapses occurred in the first
      year of life and during some of these relapses mandibular and clavicular
      involvement was noted. Prednisolone, 1 mg/kg per day, was used to treat relapses
      until 9 months of age. Indomethacin therapy at this age at a dose of 3 mg/kg per
      day allowed the cessation of prednisolone therapy and disease flares were
      thereafter infrequent and responsive to indomethacin.

PMID- 11468052
TI  - Use of intravenous hydrocortisone in Henoch-Schonlein purpura.
AB  - Henoch-Schonlein purpura should be considered in children with severe abdominal
      pain that is unresponsive to conventional treatment when no apparent cause is
      found on investigation. Such children may respond dramatically to a trial of
      intravenous corticosteroid and, hence, may avoid unnecessary investigations and
      laparotomy.

PMID- 11468053
TI  - Pancreatitis associated with Henoch-Schonlein purpura.
AB  - A 7-year-old Chinese boy presented with acute pancreatitis. The characteristic
      rash of Henoch-Schonlein purpura (HSP) did not develop until nine days later,
      together with painful scalp swelling and calf pain. Acute pancreatitis has only
      rarely been reported in association with HSP and never before as the sole
      presenting feature.

PMID- 11468054
TI  - Deceptive hyperbilirubinaemia in a newborn with familial lipoprotein lipase
      deficiency.
AB  - A rare case of familial lipoprotein lipase (LPL) deficiency in a Chinese newborn
      who presented with severe hyperbilirubinaemia is described. The falsely high
      serum bilirubin concentration was subsequently found to be a laboratory
      analytical error caused by interference of optical measurement of the lipaemic
      serum. Hypertriglyceridaemia and chylomicronaemia could be safely and effectively
      controlled by a fat-restricted diet using either modified elementary milk formula
      fortified with protein, calories and minerals, or the commercially available
      special milk formula such as Monogen or Portagen. DNA sequence analysis of the
      patient showed a Leu252Arg mutation in exon 6 of both alleles of the LPL gene.
      Although the parents were unrelated, both were heterozygous carriers of the same
      genetic defect. Codon 252 in exon 6 appears to be a common and critical site of
      mutation in the LPL gene of Chinese, but this important association has not been
      recognized previously.

PMID- 11468055
TI  - Lidocaine and heparinized saline: potential medication error.

PMID- 11468056
TI  - Economic evaluation of prophylaxis against respiratory syncytial virus infection
      in at-risk infants.

PMID- 11468058
TI  - The business of conferences.

PMID- 11468060
TI  - Musings on healthy aging.

PMID- 11468061
TI  - Developing political competence: a comparative study across disciplines.
AB  - Political activism is one way that nurses care for individuals and communities,
      and intervene in the broad range of socioeconomic factors influencing health.
      Though policy advocacy is a core public health function and a valuable nursing
      activity, the process of acquiring requisite skills and attitudes for political
      involvement is not often explored. What crucial experiences enfranchise nursing
      students toward future policy involvement? What is the student journey toward
      political competence? Do nursing students vary from students of other disciplines
      in this process? In-depth interviews were conducted with baccalaureate nursing
      students and political science students who were near graduation. Content
      analysis of interview transcripts revealed several themes. Despite rich examples
      of activism, nursing students viewed public policy as a barrier, and did not see
      connections between the personal, professional, and political. Nursing seemed
      grounded in application and service, demonstrating by involvement that they could
      "walk the walk." Political science involvement originated in theory, and resulted
      in more articulate discourse on the subject: they could "talk the talk." The data
      suggest a need for interdisciplinary dialogue, faculty modelling of political
      competence, opportunities for students to realize personal, professional, and
      political connections, and a concern of socialization in the context of global
      citizenship.

PMID- 11468062
TI  - Promoting infant health through home visiting by a nurse-managed community worker
      team.
AB  - This article describes the Resources, Education and Care in the Home program
      (REACH-Futures), an infant mortality reduction initiative in the inner city of
      Chicago built on the World Health Organization (WHO) primary health care model
      and over a decade of experience administering programs to reduce infant mortality
      through home visits. The program uses a nurse-managed team, which includes
      community residents selected, trained, and integrated as health advocates.
      Service participants were predominately African American families. All
      participants were low-income and resided in inner-city neighborhoods with high
      unemployment, high teen birth rates, violent crime, and deteriorated
      neighborhoods. Outcomes for the first 666 participants are compared to a previous
      home-visiting program that used only nurses. Participant retention rates were
      equivalent overall and significantly higher in the first months of the REACH
      Futures program. There were two infant deaths during the course of the study, a
      lower death rate than the previous program or the city. Infant health problems
      and developmental levels were equivalent to the prior program and significantly
      more infants were fully immunized at 12 months. The authors conclude that the use
      of community workers as a part of the home-visiting team is as effective as the
      nurse-only team in meeting the needs of families at high risk of poor infant
      outcomes. This approach is of national interest because of its potential to
      achieve the desired outcomes in a cost-effective manner.

PMID- 11468063
TI  - Quality care in a medicaid managed care program: adequacy of prenatal care for
      teens in Chicago.
AB  - This study considers whether obstetricians offer less adequate care to teen
      prenatal patients in the Healthy Moms, Healthy Kids (HMHK) Medicaid managed care
      program in Chicago than to non-Medicaid patients. Telephone surveys of
      obstetricians offices (n = 101) were conducted to determine the content of care
      in the first prenatal visit. These survey data are combined with demographic and
      practice background data from The American Medical Association's Physician Master
      File. Analysis indicates there were no significant differences between groups for
      receiving: (1) medical histories, (2) physical exam and tests, (3) health
      promotion counseling, and (4) availability of birthing education materials.
      Analysis further indicates, however, that teen Medicaid patients are less likely
      to receive blood tests and some urinalysis-related tests. Not receiving these
      tests is especially problematic because pregnant teens are more likely to drop
      out of the prenatal care regimen after their first visit, and teens are more
      likely to have poorer birth outcomes.

PMID- 11468064
TI  - Children and war: current understandings and future directions.
AB  - During the last decade, the number of children whose lives have been disrupted by
      war, oppression, terror, and other forms of conflict has grown tremendously. When
      the United Nations High Commission for Refugees was first established during the
      1950s to provide international protection to refugees following World War II, it
      was estimated that there were 1.5 million refugees and displaced persons. Today
      there are approximately 14 million, about three-fourths of whom are women and
      children. Although the experiences of refugee children and adolescents vary
      considerably, many have witnessed or experienced the death or murder of loved
      ones. Upon resettlement, they face numerous challenges. Research with this
      population is a relatively new area of investigation, but there is evidence that
      many of these young people experience long-term physical and emotional health
      problems. In this article, current research findings are reviewed, the widespread
      emphasis in the literature on post-traumatic stress disorder (PTSD) is critically
      examined, future research directions are suggested, and implications for public
      health nurses are addressed.

PMID- 11468065
TI  - Trumpets of attack: collaborative efforts between nursing and philanthropies to
      care for the child crippled with polio 1930 to 1959.
AB  - The purpose of this historical inquiry research was to explore (a) the
      relationship of nursing and foundations focusing on polio from 1930 to 1959; (b)
      the employment and educational opportunities arising from the polio epidemics for
      white and black nurses, as well as the obstacles encountered; (c) the role of
      nursing leaders in the care of the crippled child; and (d) the effects of the
      resolution of the polio epidemics resulting from the polio vaccine on public
      attitude and on the philanthropic organizations. Relevant journals, primary and
      secondary sources, and personal interviews were the methods used for data
      collection. Because of the extraordinary community support for work related to
      polio, nurses were able to obtain support from foundations. This support resulted
      in employment and educational opportunities for bedside nursing, primarily for
      white nurses. Middle and upper class fear of polio enabled the development of
      powerful and successful private organizations to supplement the available
      governmental services. This research illustrates the advances that nursing has
      made and reminds nurses to develop and maintain strong praxis relationships,
      alliances with philanthropies, referrals for clients with local organizations,
      and a strong voice in the planning arena.

PMID- 11468066
TI  - Starting from a blank page: discovering and creating community health nursing in
      post-Soviet Latvia.
AB  - Nurses discovering the practice and creating the tradition of community health
      nursing without mentors or forerunners have to learn from the practice itself and
      from each other. Data in the phenomenologic study of 17 Latvian community health
      nurses (CHNs) consisted of group and individual interviews and observation of
      practice with families. The focus of this article is the situated practice of
      nurses in the new role of primary care CHN, revealed through clinical stories
      that give voice to nurses in a particular historical and social context. The
      stories of the nurses in this article provide evidence of a growing ability to
      practice from a health promotion/prevention focus and engage with families and
      neighborhoods. The practice is still developing, and at this point nurses are not
      drawing on experience with families to identify and care for vulnerable
      populations.

PMID- 11468067
TI  - Urban outpost nursing: the nature of the nurses' work in the AIDS prevention
      street nurse program.
AB  - The AIDS Prevention Street Nurse Program in Vancouver, Canada focuses on HIV and
      sexually transmitted diseases (STD) prevention within a context of harm reduction
      and health promotion targeted at marginalized, hard to reach, high-risk
      populations. As part of a large evaluation project that included interviews with
      street nurses, clients, and other service providers together with document
      analysis, the nature of the street nurses' work and its fit within the provision
      of health care were described. The street nurses' work reflected the following
      themes: reaching the marginalized high-risk populations for HIV/STDs; building
      and maintaining trust, respect, and acceptance; doing HIV/AIDS and STD
      prevention, early detection, and treatment work; helping clients connect with and
      negotiate the health care system; and influencing the system and colleagues to be
      responsive. The findings and their implications for community health nursing
      practice are examined.

PMID- 11468068
TI  - Factors determining the attitudes of family caregivers of dementia patients
      toward nursing home placement in Taiwan: comparisons between urban and semiurban
      areas.
AB  - This study sought to determine the factors that influence the attitudes of family
      caregivers of dementia patients toward nursing home placement. A telephone survey
      of primary caregivers was conducted in two metropolitan areas of Taiwan.
      Caregivers of dementia patients were recruited from the neurology and psychiatry
      outpatient departments of two medical centers in Taipei (a highly urbanized area,
      n=144) and two medical centers in Kaohsiung (an area of mixed farm and nonfarm
      sectors, n=134). Family caregivers were asked if they would place patients in a
      nursing home if their dementia progressed. The mental status of dementia patients
      was the most significant variable affecting caregivers attitudes toward nursing
      home placement. Family manpower available for caregiving at home was especially
      emphasized as a determining factor affecting the decision to use nursing home
      care by primary caregivers in highly urbanized areas.

PMID- 11468091
TI  - Enhanced stress reactivity in paediatric anxiety disorders: implications for
      future cardiovascular health.
AB  - The aim was to clarify the developmental nature of associations between
      psychiatric illness and risk for cardiovascular disease by investigating
      differences in cardiac functioning between youth with anxiety disorders and
      healthy controls. Twenty-two children meeting DSM-IV criteria for either
      separation anxiety disorder, overanxious disorder, panic disorder/panic attacks,
      or social phobia and 12 healthy controls underwent continuous electrocardiogram
      and respiration rate monitoring during a 15 min baseline period and 15 min of
      exposure to 5% CO(2). Heart rate (HR) and high frequency heart rate variability
      (HRV), a non-invasive measure of cardiac parasympathetic control, were
      calculated. Youth with anxiety disorders had higher and less fluctuating HR
      during baseline. Data also suggested that probands showed diminished overall
      changes in HRV during baseline and CO(2) inhalation relative to controls.
      However, as respiration rate affects HRV, these findings were confounded by
      changes in respiration elicited by CO(2) inhalation. The data suggest that youth
      with anxiety disorders experience an elevated and less fluctuating HR in the face
      of a novel situation, possibly due to a failure to appropriately modulate HRV. In
      adults, sustained elevations in HR in conjunction with deficient vagal modulation
      predicts risk for future cardiovascular disease. As such, the current data
      suggest that the presence of an anxiety disorder may identify youth who exhibit
      autonomic profiles that place them at risk for cardiac disease.

PMID- 11468092
TI  - Is there an adequate supply of new dentists in Canada?

PMID- 11468093
TI  - Evidence-based dentistry: Part IV. Research design and levels of evidence.
AB  - Previous papers in this series on evidence-based dentistry have discussed the
      first 2 steps in seeking answers to clinical problems   formulating a clear
      question and strategically searching for evidence. The next step, critical
      appraisal of the evidence, is made easier if one understands the basic concepts
      of clinical research design. The strongest design, especially for questions
      related to therapeutic or preventive interventions, is the randomized, controlled
      trial. Questions relating to diagnosis, prognosis and causation are often studied
      with observational, rather than experimental, research designs. The strongest
      study design should be used whenever possible. Rules have been established to
      grade research evidence. This paper, the fourth in the series, presents an
      overview of research methodology most commonly used in the dental literature.

PMID- 11468094
TI  - Clinical practice guidelines in dentistry: Part I. Navigating new waters.
AB  - Clinical Practice Guidelines (CPGs) are tools, developed by and for
      practitioners, to assist in clinical decision making. They are designed to
      enhance, not replace, clinical judgement and expertise. Well-developed guidelines
      use the evidence-based approach. The research evidence related to a topic is
      assembled in a systematic, comprehensive and unbiased manner. Recommendations are
      made based on the evidence and practitioner feedback is sought prior to
      formulating the final practice guideline. There are many misperceptions about
      CPGs and some dentists are wary about their development and use. In this paper,
      we explore some of the reasons for these misperceptions, review the benefits of
      sound guidelines, and discuss some of the challenges for guideline development in
      dentistry in Canada

PMID- 11468095
TI  - Hyperbaric oxygen therapy and mandibular osteoradionecrosis: a retrospective
      study and analysis of treatment outcomes.
AB  - BACKGROUND: Hyperbaric oxygen (HBO) therapy is recognized as an adjunctive
      treatment for osteoradionecrosis (ORN). It may also be used prophylactically in
      patients who require dental extractions and are at high risk for developing ORN.
      This article reviews the treatment outcomes of patients treated with HBO therapy
      at the Toronto General Hospital from 1985 to 1997. MATERIALS AND METHODS: A total
      of 297 charts of patients treated with HBO were reviewed. Criteria assessed
      included age of patient, gender, original diagnosis, radiation dose, time between
      radiation treatment and onset of ORN, presence or absence of fracture,
      orocutaneous fistula, pain, history of a precipitating event triggering ORN,
      medical status, HBO therapy (total oxygen time, number of dives), method of
      treatment of ORN and follow-up period. Minimum patient follow-up time for
      inclusion in the study was 6 months. RESULTS: Adequate information to meet the
      inclusion criteria was obtained for 75 patients. Group A (51 patients) had been
      treated for overt ORN with HBO alone, HBO with sequestrectomy, or HBO with
      sequestrectomy and reconstruction. Group B (24 patients at risk for developing
      ORN) had been treated with HBO prophylactically for dental extractions. In group
      A, only 3 patients (5.9%) failed to show improvement. In group B, only one
      patient (4.2%) had complications during healing. CONCLUSIONS: Encouraging results
      were achieved when HBO was used in the 2 groups described above. This paper
      supports existing literature on the potential benefit of HBO as a prophylactic
      agent and adjunctive treatment of ORN.

PMID- 11468096
TI  - Replantation of avulsed primary incisors: a risk benefit assessment.
AB  - Parents of preschool children with avulsed primary incisors may request
      replantation. Although dental textbooks uniformly recommend that primary teeth
      not be replanted, some case reports advocate the procedure. This review of case
      reports identifies a number of pathological outcomes of replantation and provides
      information for clinicians and parents on the risks that may accompany
      replantation.

PMID- 11468097
TI  - Adjuncts to local anesthesia: separating fact from fiction.
AB  - Adjunctive local anesthetic techniques and their armamentaria, such as
      intraosseous injection, computer-controlled delivery systems, periodontal
      ligament injection and needleless jet injection, have been proposed to hold
      particular advantages over conventional means of achieving local anesthesia. This
      article describes the use of each technique and proprietary armamentarium and
      reviews the literature appraising their use.

PMID- 11468098
TI  - Hospital discharge databases in the surveillance of infectious diseases: Is their
      use warranted?

PMID- 11468099
TI  - Seasonal variation in the etiology of bloodstream infections in a febrile
      inpatient population in a developing country.
AB  - OBJECTIVES: Published data suggest that Streptococcus pneumoniae, non-typhi
      Salmonella species, and Mycobacterium tuberculosis are the predominant causes of
      bloodstream infection (BSI) in hospitalized populations in sub-Saharan Africa.
      This study was conducted during the wet season to ascertain the etiology and
      prevalence of BSI among febrile inpatients in a hospital where the dry season BSI
      profile in a similar study population had already been documented. METHODS: In
      the period from March to May 1998, consecutive febrile (> or = 37.5 degrees C)
      adult (> or = 14 y) patients presenting to a Malawi hospital were enrolled after
      providing informed consent. Following clinical evaluation, blood was drawn for
      culture (bacteria, mycobacteria, and fungi), human immunodeficiency virus (HIV)
      testing, and malaria smears. RESULTS: Of 238 enrolled patients, 173 (73%) were
      HIV-positive and 67 (28%) had BSI. The predominant wet season BSI pathogens were
      non-typhi Salmonella species (41%), M. tuberculosis (19%), and Cryptococcus
      neoformans (9%) (cf. the predominant dry season pathogen was S. pneumoniae).
      Mycobacteremia was more likely in HIV-positive than in HIV-negative patients
      (13/173 vs. 0/65; P < 0.05). A logistic regression model yielded clinical
      predictors of BSI that included chronic fever, oral candidiasis, or acute
      diarrhea. CONCLUSION: Pathogens causing BSI in febrile inpatients in a Malawi
      teaching hospital vary by season. Season- and country-specific studies, such as
      this one, provide data that may facilitate empirical therapy of febrile illnesses
      whose etiologies vary by season.

PMID- 11468100
TI  - Transfusion outcome in a resource-limited setting of Cameroon: a five-year
      evaluation.
AB  - OBJECTIVE: With a goal to establish strategies for improving blood safety in
      resource-limited conditions, the outcome of blood transfusion in a hospital
      setting of Cameroon was examined. METHODS: A 5-year descriptive and prospective
      study was conducted in which information on donor blood and recipients was
      obtained by direct patient observation and by examining patient notes in the
      various services of the hospital and records from the blood bank. RESULTS: Of
      40,134 donations, 35,318 (88%) were from relatives or friends of recipients. Only
      80% of all donated blood was considered safe for distribution. An average of
      about 20% of donated blood was rejected each year for positive human
      immunodeficiency virus (HIV) or hepatitis B antigen results. Other infections
      were not screened for. More than 50% of transfusions within the hospital were
      associated with an unfavorable outcome, predominantly febrile reactions and
      urticaria (40.1% and 19.4%, respectively). Acute intravascular hemolysis,
      circulatory overload, and deaths occurred in 0.01%, 0.04%, and 0.14% of cases,
      respectively. A case of post-transfusion HIV infection was also detected.
      CONCLUSIONS: Blood transfusion is still unsafe in many resource-limited
      communities of developing countries. However, it is possible to reduce some of
      these complications without sophisticated technology. Efforts to recruit more
      benevolent and autologous donors in the communities are essential.

PMID- 11468101
TI  - Bacteriology and beta-lactamase activity in acute exacerbation of chronic
      bronchitis.
AB  - OBJECTIVES: To assess the bacteriology of beta-lactamase (BL) enzyme activity in
      sputum of 40 patients with acute exacerbation of chronic bronchitis (AECB).
      METHODS: The microbiology, BL production by the different isolates, and BL
      contents in the sputum were determined. RESULTS: Eighty-four isolates were
      recovered (2.1 isolates per specimen), 44 aerobic and facultative (1.1 isolates
      per specimen), and 40 anaerobic (1.0 isolate per specimen). Aerobic bacteria were
      recovered in only 9 (22.5%) specimens, anaerobic bacteria in 9 (22.5%), and mixed
      aerobic and anaerobic bacteria were found in 22 (55%). The predominant aerobic
      isolates were Streptococcus pneumoniae (15 isolates), Haemophilus influenzae
      (11), Moraxella catarrhalis and Klebsiella pneumoniae (4 each). The predominant
      anaerobes were Peptostreptococcus sp. (19), Prevotella sp. (11), and
      Fusobacterium sp.(6). Mixed flora were present in 25 (62.5%) specimens, and the
      number of isolates varied from 2 to 5 per specimen. Thirty-nine beta-lactamase
      producing bacteria (BLPB) were isolated in 33 (82.5%) of the 40 cases. The
      predominant aerobic BLPB were H. influenzae, M. catarrhalis, K. pneumoniae,
      Staphylococcus aureus, and Escherichia coli. The predominant anaerobic BLPB were
      Prevotella sp. and Fusobacterium sp. Beta-lactamase activity was detected in 26
      (79%) of 33 of specimens in which BLPB were isolated, and in none of the seven
      specimens that did not harbor BLPB. CONCLUSIONS: The rapid detection of BL
      activity in sputum specimens may have implications for the antimicrobial
      management with AECB.

PMID- 11468102
TI  - Histopathology of cryptococcosis and other fungal infections in patients with
      acquired immunodeficiency syndrome.
AB  - OBJECTIVE: To gain insight into the histopathologic characteristics of fungal
      infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was
      conducted of the histopathology for 162 patients with evident fungal infection.
      RESULTS: The microscopic appearance of esophageal candidiasis that was common in
      patients with single organ involvement revealed necrotic debris containing
      proliferating hyphae at the site of mucosal erosions without fungal invasion of
      underlying tissue. The incidence of oral and esophageal candidiasis was followed
      by that of pulmonary aspergillosis and Candida infection. Eighteen patients had
      generalized cryptococcosis, representing the commonest generalized fungal
      disease. The essential histologic features of the disease consisted of yeast cell
      proliferation with a histiocytic response, but only minor lymphocytic and
      neutrophilic components. This was different from the manifestations of both
      Candida and Aspergillus infections. The two histologic patterns recognized in the
      pulmonary cryptococcal lesions could be graded with respect to the degree and
      type of inflammatory reaction. The milder one consisted of small scattered foci
      of intra-alveolar cryptococcal proliferation with a histiocytic response. Another
      pattern involved massive cryptococcal infection, which might be simply more
      extensive than that in the former. Capillary involvement of alveolar septa was an
      important common finding in all 18 patients.

PMID- 11468103
TI  - Comparative analysis of outcome and clinical features in children with pleural
      empyema caused by penicillin-nonsusceptible and penicillin-susceptible
      Streptococcus pneumoniae.
AB  - OBJECTIVE: To describe the clinical characteristics of pleural empyema in
      children caused by Streptococcus pneumoniae nonsusceptible to penicillin and
      compare their clinical outcome with pleural empyemas caused by penicillin
      susceptible organisms. METHODS: Records of 109 children with complicated pleural
      effusions between January 1996 and December 1998 were retrospectively reviewed.
      RESULTS: Pathogens were recovered in 45 of these cases. Streptococcus pneumoniae
      represented 71% of the isolates, with 20 (62%) and 12 (38%) of the strains
      proving susceptible and nonsusceptible to penicillin, respectively. The average
      age for children with penicillin-nonsusceptible infections was 18.3 months
      compared with an average age of 40.9 months for those with penicillin-susceptible
      infections (P = 0.03). Previous antibiotic treatment was more frequent in
      children with penicillin-nonsusceptible organisms (P = 0.05). No significant
      differences were found between the two groups for gender, underlying diseases,
      duration of fever and tachypnea, need of surgical treatment, bacteremia
      incidence, mean duration of therapy, or length of hospital stay. CONCLUSIONS:
      Pleural empyemas caused by penicillin-nonsusceptible S. pneumoniae appear to be
      associated with younger age and previous antibiotic treatment. By contrast, the
      outcome was not influenced by the penicillin susceptibility of the pneumococcus
      strains.

PMID- 11468104
TI  - Antibodies to Trypanosoma cruzi among blood donors in Buenos Aires, Argentina.
AB  - OBJECTIVES: The aim of this work was to study the prevalence of anti-Trypanosoma
      cruzi in the blood donor population in Buenos Aires, to compare the relative
      sensitivity and specificity of the two screening tests used and to confirm the
      results with a third assay. MATERIAL AND METHODS: Between May 1995 and July 1999,
      64,887 blood donor consecutive samples were screened with the following
      commercial tests: indirect hemagglutination (IHA) (Polychaco, Buenos Aires,
      Argentina) and enzyme-linked immunosorbent assay (ELISA) (40,222 with Chagatek,
      Organon Teknika, Buenos Aires, Argentina, and 24,665 with Chagas EIA, Abbott, Sao
      Paulo, Brazil). Repeatedly reactive samples in one or both tests were analyzed
      with a third method: dot blot (Bio Chagas, Gador, Buenos Aires, Argentina) or
      particle agglutination (Serodia, Fujirebio, Tokyo, Japan). Sera that reacted in
      at least two tests were considered positive. RESULTS: The seroprevalence was
      2.66% (1744 samples were reactive for one or both screening tests), and 1.46%
      (949 samples) were confirmed positive. The ELISAs proved to be more sensitive
      (relative sensitivity: 99.67-99.71%) whereas 192 samples (0.47%) were IHA false
      negatives (relative sensitivity: 79.77%). Relative specificity for EIA was 98.47-
      99.23% and for IHA 99.85%. CONCLUSIONS: Results suggest the need of performing
      two screening tests for Chagas disease in blood banks from endemic areas and the
      importance of a third confirmatory assay to avoid unnecessary medical counseling.

PMID- 11468105
TI  - Tuberculosis and drug resistance among patients seen at an AIDS Reference Center
      in Sao Paulo, Brazil.
AB  - OBJECTIVES: To assess the frequency of resistance of Mycobacterium tuberculosis
      to antituberculosis drugs and the factors associated with it among patients with
      tuberculosis (TB) and acquired immunodeficiency syndrome (AIDS). MATERIALS AND
      METHODS: The medical records of TB and AIDS cases diagnosed from 1992 to 1997 in
      a public service for AIDS care were reviewed. RESULTS: Resistance was diagnosed
      in 82 (19%) of 431 cases. The mean and median values between the diagnosis of
      AIDS and the diagnosis of TB were 214.8 days and 70.5 days, respectively.
      Multidrug-resistant TB (MDR TB) occurred in 11.3% of cases. Of the 186 patients
      with no previous treatment, 13 (6.9%) presented primary MDR TB. Of the 90 cases
      with previous treatment, six (6.7%) presented monoresistance to rifampin and 27
      (30%) presented MDR TB. The distribution of cases with sensitive and resistant M.
      tuberculosis strains was homogeneous in terms of the following variables: gender,
      age, category of exposure to human immunodeficiency virus (HIV), alcoholism, and
      homelessness. Multivariate analysis showed an association between resistance and
      the two following variables: previous treatment and duration of AIDS prior to TB
      exceeding 71 days. The rates of primary multiresistance and of monoresistance to
      rifampin were higher than those detected in HIV-negative patients in Brazil.
      CONCLUSIONS: In this patient series, M. tuberculosis resistance was predominantly
      of the acquired type, and resistance was independently associated with previous
      treatment for TB and with duration of AIDS prior to TB exceeding 71 days.

PMID- 11468106
TI  - Fatal unrecognized cutaneous and systemic Kaposi's sarcoma in an AIDS patient
      with acute cryptococcal meningoencephalitis.

PMID- 11468107
TI  - Wound zygomycosis: two cases with unusual manifestations.

PMID- 11468108
TI  - Primary actinomycosis of the hand: a case report and literature review.

PMID- 11468109
TI  - Lamivudine therapy for chronic hepatitis B virus infection and pregnancy: a case
      report.

PMID- 11468110
TI  - Problems and risks of unsolicited e-mails in patient-physician encounters in
      travel medicine settings.
AB  - BACKGROUND: International travel and use of modern information technology are
      expressions of modern life style. Seeking on-line travel health advice via E-mail
      for preventive (teleprevention) or diagnostic reasons may become increasingly
      popular among patients with financial resources and Internet access. This study
      was undertaken to compare the behavior of travel clinic or tropical medicine
      physicians and other providers of travel-related medical information services
      toward unsolicited E-mails from fictitious patients in pretravel and post-travel
      scenarios. We also wanted to test the potential of E-mail advice for preventive
      medicine (teleprevention), and to find out how the "Good Samaritan Law" is
      observed. METHODS: Two different E-mails were posted to E-mail addresses of 171
      physicians (members of travel health and/or tropical medicine societies) and
      services offering advice on travel health issues identified by an AltaVista
      search. These E-mails, from two different fictitious travelers, were asking for
      advice regarding malaria prophylaxis in a pretravel scenario and describing
      symptoms suggesting acute malaria. RESULTS: Of the contacted addresses 43.3% and
      49.7% respectively, replied to the pre- and post-travel E-mail. Of those
      suggesting antimalarial chemoprophylaxis in the pretravel scenario, 13.2%
      proposed inadequate regimens, and at least 3.5% of the post-travel replies were
      inappropriate. The "Good Samaritan Law" was observed by a significant number of
      physicians. CONCLUSION: Both patients and physicians have to be aware of the
      limitations of E-mail communication. Guidelines protecting physicians against
      legal and ethical consequences of this new communication technology are urgently
      needed.

PMID- 11468111
TI  - Malaria antibodies and mefloquine levels among United Nations troops in Angola.
AB  - BACKGROUND: The United Nations deployed about 8,000 soldiers in a peacekeeping
      mission in Angola. Malaria is the most common disease there and consequently it
      was the major risk to the UN troops. Most of them are from malaria free areas. As
      a result of improper prophylactic measures there were many cases of malaria,
      including some deaths in 1995. In February-March 1996, an Israeli team was sent
      to Angola to evaluate the malaria situation among UN soldiers. This paper deals
      specifically with some aspects of chemoprophylaxis and diagnosis. The efforts
      were concentrated in one particular area where malaria incidence had been
      reported as the highest. METHODS: Blood samples were collected from nonimmune
      soldiers who were using mefloquine as a prophylactic drug and were exposed to
      malaria. The mefloquine and the antimalarial antibody plasma levels were
      monitored. RESULTS: While the local laboratory indicated that about 80% had a
      malaria episode, the serological results revealed that only 5 soldiers of the 56
      (9%) examined had antimalarial antibodies, of which 3 were Angolans. Despite a
      controlled prophylactic regimen there was considerable variability in mefloquine
      plasma levels: 46% of the samples were below the required prophylactic level and
      26% above it. All patients who were proven positive with malaria by both
      microscopic and serologic observation had a low level of mefloquine. CONCLUSIONS:
      In field conditions, a kit which identifies plasmodial antigens, is preferable,
      to a microscopic diagnostic method. Controlled mefloquine prophylaxis may not
      prevent malaria, especially when blood levels are low. The reason for the low
      mefloquine blood levels is not clear and needs further evaluation.

PMID- 11468112
TI  - Medical evacuations and fatalities of United Nations High Commissioner for
      Refugees field employees.
AB  - BACKGROUND: Over the last 20 years, the number of conflicts and humanitarian
      interventions has steadily increased, as has the level of insecurity on operation
      sites. So far, little information is available concerning the morbidity and
      mortality of expatriates and local employees working in the field for
      humanitarian agencies. METHODS: A retrospective study was conducted in order to
      review the causes of medical evacuations and deaths of the United Nations High
      Commissioner for Refugees field employees. All medical records reported to the
      headquarter's medical services over 2 years (1994-1995) were collated and
      analyzed. RESULTS: A total of 199 cases (162 medical evacuations, 37 deaths) was
      reported over these 2 years for a monthly average of 4,151 field employees.
      Ninety-four men and 68 women were evacuated, 34 men and 3 women died. Expatriate
      employees represented two-thirds of the cases. Expatriates from Europe, North
      America, and Japan represented 58 in 122 evacuated expatriates and 2 in 9 deaths
      of expatriates. The major causes for evacuation were infectious diseases (17%),
      obstetric-gynecological conditions (15%), accidents (15%), ophthalmology/ear,
      nose, throat/dentistry (11%), gastrointestinal diseases (10%). The major causes
      of fatalities were infectious diseases (41%), cancer (24%), accidents (16%),
      cardiovascular diseases (11%). Firearms caused 4 fatalities and 2 medical
      evacuations. Fifty-nine percent of the cases occurred in Africa. CONCLUSIONS:
      Infectious diseases remain a leading cause of fatalities and medical evacuations,
      particularly AIDS-related diseases among local African employees. A large number
      of accidents and obstetric-gynecological conditions was also noted. Special
      emphasis should be put on preventive measures and access to health care for
      nationals. Systematic data collection and surveillance would help in designing
      properly adapted strategies to minimize risks for relief workers in the field.

PMID- 11468113
TI  - Early rabies antibody response to intramuscular booster in previously
      intradermally immunized travelers using human diploid cell rabies vaccine.
AB  - BACKGROUND: Postexposure treatment (PET) of travelers who may have had a
      potential rabies exposure is simpler, safer, and cheaper if the traveler is
      preimmunized. Preimmunization can be done with human diploid cell rabies vaccine
      (HDCV) administered intramuscularly or intradermally. Some authorities, however,
      are now advocating that travelers vaccinated by the intradermal (ID) route should
      be treated as if they are not immunized. A particular concern raised is that
      travelers who have received pre-exposure rabies vaccination intradermally, may
      have a delayed response to postexposure boosters. This study is designed to
      elucidate whether a single intramuscular (IM) HDCV booster will provoke an early
      (day 5) immune response in individuals given pre-exposure ID HDCV. METHODS:
      Twenty-nine travelers who had received a course of three 0.1 mL ID HDCV between
      12 and 24 months previously were given a single 1.0 mL IM booster of HDCV. Rabies
      antibody levels were compared 5 days later to those before the booster. RESULTS:
      Twenty-five of the 29 subjects (86%) showed an adequate rise in virus
      neutralizing antibody (VNA) titer 5 days after booster. Nine of the 29 subjects
      (31%) had inadequate antibody levels prior to the simulated postexposure booster.
      Five days after the postexposure booster, 27 of 29 (93%) had adequate antibody
      levels. The other 2 travelers were subsequently shown to have adequate VNA levels
      when tested 4 and 6 weeks later, respectively. CONCLUSION: For travelers who were
      given pre-exposure ID HDCV vaccination within the last 2 years and received one
      IM postexposure booster dose of HDCV, most mounted an adequate early immune
      response. This data does not support a change in current recommendations for
      rabies PET in this group. Further research to ascertain the duration of
      protection of pre-exposure ID rabies immunization is required.

PMID- 11468114
TI  - Deep venous thrombosis associated with corporate air travel.
AB  - BACKGROUND: Deep venous thrombosis (DVT) is commonly seen among bedridden and
      postoperative patients. Its association with travel may also make DVT an
      occupational health risk to otherwise healthy business travelers. We estimated
      the incidence of and risk factors for DVT among 8,189 World Bank employees and a
      subset of 4,951 international business travelers. METHODS: Occurrence of DVT
      between 1995 and 1998 was determined using 1) medical insurance claims; 2)
      Workers' Compensation claims; and 3) intra-office E-mail solicitation followed by
      interview. For each insurance claim case, 10 controls were randomly selected from
      among World Bank employees insured during the same month and year as the case's
      claim was filed, and case-control analyses were performed to identify potential
      predictors or risk factors for DVT. RESULTS: Thirty individuals filed claims for
      DVT of the legs (annual incidence rate: 0.9 per 1,000 employees); three of these
      claims were filed within 30 days after a travel mission. Two employees reported
      DVT as a Workers' Compensation injury, and five staff with verified DVT
      participated in interviews. After controlling for age and gender, no association
      with any travel-related covariate was seen. Results of analyses considering all
      thrombophlebitis and thromboembolism followed the same pattern. The average
      annual incidence of DVT occurring within 30 days of mission among traveling staff
      ranged from 0.10 per 1,000 to 0.25 per 1,000 travelers, depending on the case
      finding method. CONCLUSION: No association between DVT and travel was observed
      after adjustment for gender and age. These results, however, are preliminary, and
      due to the rarity of DVT, based on small numbers.

PMID- 11468115
TI  - Department of Defense doctrine and materiel for protecting personnel from biting
      arthropods.

PMID- 11468116
TI  - Ciguatera fish poisoning: an emerging syndrome in Italian travelers.

PMID- 11468117
TI  - Chronic watery diarrhea due to co-infection with Cryptosporidium spp and
      Cyclospora cayetanensis in a Swiss AIDS patient traveling in Thailand.

PMID- 11468118
TI  - Diplomats in Bangkok and risk of melioidosis.

PMID- 11468119
TI  - Prolonged visual illusions induced by mefloquine (Lariam): a case report.

PMID- 11468120
TI  - A fatal jellyfish encounter in the Gulf of Siam.

PMID- 11468121
TI  - Tuberculin testing in a remote area of Zanskar Ladakh, India.

PMID- 11468122
TI  - Proposal for a new scoring system in international interhospital air transport.

PMID- 11468125
TI  - Toxicity of beta-carotene and its exacerbation by acetaldehyde in HepG2 cells.
AB  - In rats and baboons, the hepatotoxicity of chronic ethanol consumption is
      exacerbated by beta-carotene feeding, but the mechanism of this adverse effect is
      unknown. In this study, the toxicity of beta-carotene and acetaldehyde was
      documented by the MTT test (an assay of reduction of tetrazolium to formazan) and
      by lactate dehydrogenase (LDH) leakage. In HepG2 cells, beta-carotene or
      acetaldehyde inhibited mitochondrial reduction function as indicated by a
      decrease of the MTT test. beta-Carotene was inhibitory at very low concentration,
      in a dose-dependent manner. The combination of these two compounds resulted in an
      additive effect. Acetaldehyde increased LDH leakage from the HepG2 cells into the
      medium, whereas beta-carotene by itself did not show such an effect, but it
      exacerbated the toxicity of acetaldehyde when combined. In addition, this study
      showed that acetaldehyde and beta-carotene inhibited each other's clearance from
      the medium, which suggests that these two chemicals may share, at least in part,
      a common metabolic pathway (possibly via aldehyde dehydrogenase) in the cells,
      and that a competitive inhibition may exist. In conclusion, this preliminary
      study indicates that beta-carotene is toxic to hepatocytes, especially when
      combined with acetaldehyde, the metabolite of ethanol.

PMID- 11468126
TI  - Effects of repeated morphine treatment on metabolism of cerebral dopamine and
      serotonin in alcohol-preferring AA and alcohol-avoiding ANA rats.
AB  - The alcohol-preferring AA (Alko Alcohol) rats are more rapidly sensitized to the
      locomotor activity-stimulating effects of small doses of morphine than the
      alcohol-avoiding ANA (Alko Non-Alcohol) rats. To study the involvement of
      dopaminergic and serotonergic transmission in this behaviour, the effects of
      acute morphine (1 mg/kg) challenge on the concentrations of dopamine (DA), 5
      hydroxytryptamine (5-HT, serotonin) and their metabolites were estimated in three
      dopaminergic areas in AA and ANA rats on the fourth day after a 3-day morphine or
      saline treatment. Acute administration of morphine enhanced DA metabolism in the
      caudate-putamen in the AA, but not in the ANA, rats; in the nucleus accumbens and
      in the olfactory tubercle the acute effect of morphine was similar in rats of
      both lines. Morphine pretreatment did not significantly enhance acute morphine's
      effects on DA metabolites in any of the brain areas studied in rats of either
      line. Acute administration of morphine enhanced brain 5-HT metabolism in the AA
      rats but not in the ANA rats, but after repeated treatment it induced no
      enhancement of 5-HT metabolism. With the methods used, no significant differences
      were found between the AA and ANA rats in the effects of repeated morphine on
      cerebral dopaminergic or serotonergic mechanisms which could account for the
      different behavioural sensitization found previously in rats of these lines.
      However, both monoamines studied might be involved in the acute locomotor
      stimulatory effects of morphine.

PMID- 11468127
TI  - Ethanol facilitation of short-term memory in adult rats with a disturbed
      circadian cycle.
AB  - The aim of this study was to evaluate the effect of 3-month ethanol treatment on
      olfactory social memory test performance using two inter-exposure intervals [30
      min: short-term recognition (STR); or 120 min: long-term recognition (LTR)] in
      adult rats with a disturbed circadian cycle (DCC). Ethanol treatment both in
      ethanol-preferring and -non-preferring groups improved the STR task compared to
      control rats. However, LTR procedure triggered the opposite tendency. Moreover,
      no differences between control rats with DCC and those with normal diurnal rhythm
      in STR and LTR paradigms were observed. Our results suggest that, under some
      conditions, alcohol facilitates short-term memory in adult rats.

PMID- 11468128
TI  - The effects of a liquid ethanol diet on nutritional status and fluid balance in
      the rat.
AB  - The liquid ethanol diet is a widely used method of ethanol administration. The
      purpose of this study was to evaluate fluid balance using a multitude of
      physiological parameters (electrolytes, osmolality, total serum proteins, fluid
      intake/output and body weight), during and after the introduction of liquid
      ethanol diet. Animals were randomized into four different dietary protocols (two
      control and two ethanol groups) and were placed in metabolic cages for 16 days.
      Serum electrolytes, as well as the above parameters, were measured before, during
      and 1 week after the introduction of 9% (v/v) ethanol-containing diet (Lieber
      DeCarli: LD). After the first night on 9% (v/v) ethanol LD, animals had
      significantly decreased diet consumption, urine output and body weight. However,
      a major finding of this study was that, during the habituation phase, the
      electrolyte values remained within the normal range for rats and, in particular,
      serum sodium was not altered at any time point measured in this study. Based upon
      the findings from this study, it is recommended that body weight be carefully
      monitored as a measure of the animal's equilibration and physiological adaptation
      during the initiation of a liquid ethanol diet, since neither the serum sodium
      nor calculated osmolality values were changed. Our results also highlight the
      need to offer water to animals during the habituation phase of ethanol
      consumption. This is because ethanol rats that were offered water ad libitum lost
      less weight than groups that did not receive water ad libitum, despite consuming
      the same amount of LD diet.

PMID- 11468129
TI  - Opposite effects of acute and chronic administration of alcohol on gastric
      emptying and small bowel transit in rat.
AB  - The effects of acute and chronic administration of a large dose of alcohol on
      gastric emptying and small bowel transit were studied in rats. The development of
      tolerance to the acute effect of alcohol on gastrointestinal motility during
      chronic alcohol administration was also investigated. Gastric emptying and small
      intestinal transit were assessed by the Phenol Red recovery method. Acutely,
      ethanol was given in a dose of 2.5 g/kg body wt by gavage 30 min before the test
      meal. Chronically, ethanol was administered by two different methods: (1) a dose
      of 2.5 g/kg body wt was administered by gavage daily for 10 days; (2) animals
      received 15% ethanol in their drinking water for 30 days. A single large dose of
      alcohol inhibited gastric emptying and small bowel transit. Treatment with a
      large dose of alcohol for 10 days did not change the gastric emptying
      significantly, but inhibited the small intestinal transit. Alcohol consumption in
      drinking water for 30 days accelerated gastric emptying and small bowel transit.
      Tolerance to the acute inhibitory effect of a single large dose of alcohol on
      gastrointestinal motility did not develop during chronic alcohol treatment.

PMID- 11468130
TI  - Changes in ethanol preference by rats treated with gamma1 and gamma2 GABA(A)
      receptor subunit antisense oligodeoxynucleotides.
AB  - Micro-injections (10 nmol/day over 5 days) of antisense oligodeoxynucleotides
      (aODNs) to gamma-aminobutyric acid A (GABA(A)) receptor alpha1 and gamma2
      subunits reduce the mRNA for these subunits in rat brain. In this study, the
      effects of alpha1 and gamma2 subunit aODNs on rat alcohol preference were
      investigated. Reduction of the alpha1 subunit mRNA decreased, whereas reduction
      of the gamma2 subunit mRNA increased, ethanol intake in rats.

PMID- 11468131
TI  - The effect of long-term ethanol feeding on Brucella melitensis infection of rats.
AB  - The adverse effects of ethanol on Brucella melitensis have not been studied
      previously. In this study, a new model of B. melitensis infection was used in the
      setting of chronic ethanol administration in rats. It was found that the
      chronically ethanol-receiving rats exposed to B. melitensis infection had
      significantly greater numbers of B. melitensis in their spleen and liver than the
      rats in the control group.

PMID- 11468132
TI  - Alcohol preference: association with reduced striatal nicotinic receptors.
AB  - This study was designed to determine whether inherent alcohol preference is
      associated with differential expression of central nicotinic receptors.
      [(3)H]Cytisine and [(125)I]alpha-bungarotoxin binding-site, ligands selective for
      alpha4beta2 and alpha7 nicotinic receptor subtypes, respectively, were determined
      in various brain regions of alcohol-preferring (P) and non-preferring (NP) rats.
      Only the striatum of P rats had a reduction in the number of binding sites for
      both ligands, compared to NP rats. The data suggest a link between striatal
      nicotinic receptors and alcohol preference.

PMID- 11468133
TI  - Altered frontal lobe function suggested by source analysis of event-related
      potentials in impulsive violent alcoholics.
AB  - Scalp-recorded event-related potentials (ERPs) are sensitive indicators of subtle
      alterations in cerebral processes. We assessed automatic auditory adaptation and
      detection of novel stimuli in violent and non-violent alcoholics and normal
      subjects. Source analysis of ERPs revealed active medial temporal and frontal
      regions in all subjects. Frontal lobe processed alerting tones in violent
      alcoholics, whereas non-violent alcoholics and normal subjects processed them in
      medial temporal brain areas. Detection of deviant tones appeared simultaneously
      in frontal and temporal areas in violent alcoholics, but sequentially in other
      groups. These findings imply alterations in arousal and involuntary adaptive
      processes in cortical networks associated with violent behaviour and alcoholism.

PMID- 11468134
TI  - Flupenthixol decanoate and relapse prevention in alcoholics: results from a
      placebo-controlled study.
AB  - Flupenthixol, with its broad receptor profile, interacts with a variety of
      dopamine and serotonin binding sites which are important in the neurobiology of
      alcohol dependence. Its pharmacology, together with encouraging results from both
      animal studies and clinical trials with cocaine users, led us to postulate that
      flupenthixol would significantly prevent relapse in detoxified alcohol-dependent
      individuals. We conducted a prospective, randomized, double-blind, placebo
      controlled, multi-centre trial with two parallel groups and appropriate
      statistical evaluation. Subjects met criteria for moderate to severe alcohol
      dependence (DSM-III-R), without any concomitant psychiatric disorder. After
      complete detoxification, 281 women and men received either 10 mg of flupenthixol
      decanoate or placebo as i.m. injection every second week for 6 months on an out
      patient basis, followed by 6 months of follow-up. Efficacy was based on absolute
      abstinence, with relapse being defined as consumption of any alcohol after
      inclusion in the study. In contrast to the hypothesis, flupenthixol did not
      reduce, but was associated with more, relapses. Though well tolerated, relapse
      rates after 6 months of treatment were 85.2% (flupenthixol) versus 65.5%
      (placebo), a highly significant difference from the medication. Flupenthixol was
      also inferior to placebo with regard to other secondary criteria of efficacy
      (cumulative abstinence duration, relapse rate after 12 months). These results
      indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial
      effect on abstinence maintenance in alcohol-dependent individuals.

PMID- 11468135
TI  - Prevalence and mortality of heavy drinkers in a general medical hospital unit.
AB  - This study was performed in order to analyse the prevalence, clinical
      characteristics and mortality of heavy drinkers among hospitalized patients
      during a 2-year period. Chronic excessive alcohol consumption (daily intake >80 g
      of ethanol for males and >40 g for females) was found in 278 of 2913 hospital
      admissions and was strongly associated with the male sex (90.69%). Heavy drinkers
      were significantly younger than other admissions (15 and 10 years for men and
      women, respectively), but showed similar mortality rates to other admissions,
      despite a much earlier age at death (19.5 years for men and 22 years for women).
      There was a trend towards higher mortality rates among severe alcoholic women
      than severe alcoholic men and non-alcoholic women. Liver cirrhosis was the entity
      most frequently observed in the heavy drinkers, and was significantly more
      prevalent in alcoholic women.

PMID- 11468136
TI  - Association of self-reported diseases and health care use with commonly used
      laboratory markers for alcohol consumption.
AB  - The relationships of carbohydrate-deficient transferrin (CDT), gamma
      glutamyltransferase (GGT) and their mathematical combination (gamma-CDT) with
      self-reported diseases were evaluated in a large cross-sectional risk factor
      survey. Significant gender effects were observed in associations of the markers
      with several medical conditions as well as with general health care utilization.
      In men, CDT was associated with rheumatoid arthritis. In both genders, GGT was
      positively associated with hypertension and diabetes. gamma-CDT was positively
      associated with hypertension in males and with asthma in females. This general
      population study demonstrates that these markers, although most commonly used to
      assess alcohol misuse, might also serve as health risk indicators.

PMID- 11468137
TI  - Blood flow velocity in the middle cerebral artery in heavy alcohol drinkers.
AB  - The aim of this study was to assess if heavy alcohol drinking influences blood
      flow velocity in cerebral arteries. Blood flow velocity (V(mean)) in the middle
      cerebral artery was measured by transcranial Doppler sonography (TCD) in heavy
      alcohol drinkers. Significantly decreased V(mean) was found in comparison with
      healthy volunteers.

PMID- 11468138
TI  - The combined use of the early detection of alcohol consumption (EDAC) test and
      carbohydrate-deficient transferrin to identify heavy drinking behaviour in males.
AB  - The aim of this study was to determine the efficacy of the combined use of
      carbohydrate-deficient transferrin (CDT) and the Early Detection of Alcohol
      Consumption (EDAC) test to assess heavy drinking in a population of males (n =
      187) drinking an average of 20 drinks per day. Heavy drinkers (n = 138) and light
      drinkers (n = 49) were analysed in three ways: using the EDAC test alone, using
      the CDT test alone and using the EDAC and CDT tests combined. The EDAC method
      uses linear discriminant function to analyse a battery of routine laboratory
      tests that generate a score for each subject and its associated probability
      value. This translates into the likelihood of each individual being a heavy or a
      light drinker. CDT uses ion-exchange chromatography to extract CDT in the serum
      and quantifies it by radioimmunoassay. The EDAC alone showed 88% (122/138)
      sensitivity rate when identifying heavy drinking males and 98% (48/49)
      specificity rate when assessing light drinkers. The CDT test alone showed a
      sensitivity rate of 58% (80/138) and a corresponding specificity rate of 96%
      (47/49). When analysed in parallel, 92% (127/138) of heavy drinkers showed
      abnormal EDAC and/or CDT tests and 94% (46/49) of light drinkers were negative
      for both tests. When analysed sequentially, the CDT test confirmed 61% (75/122)
      of the heavy drinkers identified by the EDAC test. Specificity rate for this
      testing strategy was 100%, because the only false positives for EDAC tested
      negative for CDT. This preliminary study shows that EDAC and CDT may react
      independently to alcohol intake and can be combined for maximum diagnostic
      accuracy.

PMID- 11468140
TI  - Does telomere shortening count?

PMID- 11468141
TI  - Bacillus Calmette-Guerin sepsis: shift of an intended local toward a detrimental
      systemic cytotoxic immune response.

PMID- 11468143
TI  - Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to
      clinical scale from a single blood draw using dendritic cells and HLA-tetramers.
AB  - Cytomegalovirus (CMV) reactivation in immunocompromised recipients of allogeneic
      stem cell transplantation is a cause of morbidity and mortality from viral
      pneumonitis. Antiviral drugs given to reactivating patients have reduced the
      mortality from CMV but have toxic side effects and do not always prevent late CMV
      disease. Cellular immunotherapy to prevent CMV disease is less toxic and could
      provide prolonged protection. However, a practical approach to generating
      sufficient quantities of CMV-specific cytotoxic T cells (CTLs) is required. This
      study describes a system for generating sufficient CMV-specific CTLs for adoptive
      immunotherapy of HLA-A*0201 bone marrow transplant recipients from 200 mL donor
      blood. Donor monocytes are used to generate dendritic cells (DCs) in medium with
      autologous plasma, interleukin 4, granulocyte-macrophage colony-stimulating
      factor, and CD40 ligand. The DCs are pulsed with the immunodominant HLA-A*0201
      restricted CMV peptide pp65(495-503), and incubated with donor T cells. These
      cultures are restimulated twice with peptide-pulsed lymphoblastoid cell lines
      (LCLs) or CD40-ligated B cells and purified with phycoerythrin (PE)-labeled
      pp65(495-503)/HLA-A*0201 tetramers by flow sorting, or with anti-PE paramagnetic
      beads. The pure tetramer-positive population is then rapidly expanded to obtain
      sufficient cells for clinical immunotherapy. The expanded CTLs are more than 80%
      pure, of memory phenotype, with a Tc1 cytokine profile. They efficiently kill CMV
      infected fibroblasts and express the integrin VLA-4, suggesting that the CTLs
      could cross endothelial barriers. This technique is reproducible and could be
      used for generating CMV-specific CTLs to prevent CMV disease after allogeneic
      blood and marrow transplantation. (Blood. 2001;98:505-512)

PMID- 11468144
TI  - Genomic and proteomic analysis of the myeloid differentiation program.
AB  - Although the mature neutrophil is one of the better characterized mammalian cell
      types, the mechanisms of myeloid differentiation are incompletely understood at
      the molecular level. A mouse promyelocytic cell line (MPRO), derived from murine
      bone marrow cells and arrested developmentally by a dominant-negative retinoic
      acid receptor, morphologically differentiates to mature neutrophils in the
      presence of 10 microM retinoic acid. An extensive catalog was prepared of the
      gene expression changes that occur during morphologic maturation. To do this, 3'
      end differential display, oligonucleotide chip array hybridization, and 2
      dimensional protein electrophoresis were used. A large number of genes whose mRNA
      levels are modulated during differentiation of MPRO cells were identified. The
      results suggest the involvement of several transcription regulatory factors not
      previously implicated in this process, but they also emphasize the importance of
      events other than the production of new transcription factors. Furthermore, gene
      expression patterns were compared at the level of mRNA and protein, and the
      correlation between 2 parameters was studied. (Blood. 2001;98:513-524)

PMID- 11468145
TI  - H ferritin knockout mice: a model of hyperferritinemia in the absence of iron
      overload.
AB  - Ferritin, the iron-storing molecule, is made by the assembly of various
      proportions of 2 different H and L subunits into a 24-mer protein shell. These
      heteropolymers have distinct physicochemical properties, owing to the ferroxidase
      activity of the H subunit, which is necessary for iron uptake by the ferritin
      molecule, and the ability of the L subunit to facilitate iron core formation
      inside the protein shell. It has previously been shown that H ferritin is
      indispensable for normal development, since inactivation of the H ferritin gene
      by homologous recombination in mice is lethal at an early stage during embryonic
      development. Here the phenotypic analysis of the mice heterozygous for the H
      ferritin gene (Fth(+/-) mice) is reported, and differences in gene regulation
      between the 2 subunits are shown. The heterozygous Fth(+/-) mice were healthy and
      fertile and did not present any apparent abnormalities. Although they had iron
      overloaded spleens at the adult stage, this is identical to what is observed in
      normal Fth(+/+) mice. However, these heterozygous mice had slightly elevated
      tissue L ferritin content and 7- to 10-fold more L ferritin in the serum than
      normal mice, but their serum iron remained unchanged. H ferritin synthesis from
      the remaining allele was not up-regulated. This probably results from subtle
      changes in the intracellular labile iron pool, which would stimulate L ferritin
      but not H ferritin synthesis. These results raise the possibility that reduced H
      ferritin expression might be responsible for unexplained human cases of
      hyperferritinemia in the absence of iron overload where the hereditary
      hyperferritinemia-cataract syndrome has been excluded. (Blood. 2001;98:525-532)

PMID- 11468146
TI  - Chemoattractants MDC and TARC are secreted by malignant B-cell precursors
      following CD40 ligation and support the migration of leukemia-specific T cells.
AB  - The use of tumor cells as vaccines in cancer immunotherapy is critically
      dependent on their capacity to initiate and amplify tumor-specific immunity.
      Optimal responses may require the modification of the tumor cells not only to
      increase their immunogenicity but also to improve their ability to recruit
      effector cells to the tumor sites or sites of tumor antigen exposure. It has been
      reported that CD40 cross-linking of acute lymphoblastic leukemia (ALL) cells
      significantly increases their immunogenicity and allows the generation and
      expansion of autologous antileukemia cytotoxic T lymphocytes. This study
      demonstrates that the CD40 ligation of these tumor cells also induces the
      secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells
      cultured in the presence of sCD40L promote the migration of activated T cells
      that express CCR4, the common specific receptor for MDC and TARC. More
      importantly, the supernatants from CD40-stimulated tumor cells also support the
      transendothelial migration of autologous CCR4(+) antileukemia T cells. Therefore,
      the results demonstrate that the delivery to leukemia cells of a single
      physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor
      cell immunogenicity and induces potent chemoattraction for T cells. (Blood.
      2001;98:533-540)

PMID- 11468147
TI  - HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is
      abolished by inhibition of the p38 mitogen-activated protein kinase signaling
      pathway.
AB  - It has been previously shown that the HIV-1 envelope glycoprotein 120 (gp120)
      activates cell signaling by CXCR4, independently of CD4. The present study
      examines the involvement of different intracellular signaling pathways and their
      physiopathologic consequences following the CD4-independent interaction between
      CXCR4 or CCR5 and gp120 in different cell types: primary T cells, CD4(
      )/CXCR4(+)/CCR5(+) T cells, or glioma cells. These interactions were compared
      with those obtained with natural ligands, stromal cell-derived factor 1 alpha
      (SDF-1alpha) (CXCL12) and macrophage inflammatory protein 1 beta (MIP-1beta)
      (CCL4) of their respective coreceptors. Thus, both p38 and SAPK/Jun N-terminal
      kinase mitogen-activated protein kinases (MAPKs) are activated on stimulation of
      these cells with either T- or M-tropic gp120, as well as with SDF-1alpha or MIP
      1beta. In contrast, extracellular signal-related kinase 1 and 2 MAPKs are only
      activated by MIP-1beta but not by M-tropic gp120. Importantly, T- and M-tropic
      gp120 are able to induce the secretion of matrix metalloproteinase 9 (MMP-9), an
      extracellular metalloproteinase present in cerebrospinal fluid of patients with
      HIV-1 by T cells or glioma cells. Specific inhibition of MAPK p38 activation
      resulted in a complete abrogation of the induction of the MMP-9 pathogenic factor
      expression by gp120 or chemokines in both cell types. Because neurodegenerative
      features in acquired immune deficiency syndrome dementia may involve
      demyelinization by MMP-9, the specific targeting of p38 could provide a novel
      means to control HIV-induced cytopathogenic effects and cell homing to viral
      replication sites. (Blood. 2001;98:541-547)

PMID- 11468148
TI  - Postremission therapy in older patients with de novo acute myeloid leukemia: a
      randomized trial comparing mitoxantrone and intermediate-dose cytarabine with
      standard-dose cytarabine.
AB  - The treatment of older patients with acute myeloid leukemia (AML) remains
      unsatisfactory, with complete remission (CR) achieved in only approximately 50%
      and long-term disease-free survival in 10% to 20%. Three hundred eighty-eight
      patients (60 years of age and older) with newly diagnosed de novo AML were
      randomly assigned to receive placebo (P) or granulocyte-macrophage colony
      stimulating factor (GM-CSF) or GM in a double-blind manner, beginning 1 day after
      the completion of 3 days of daunorubicin and 7 days of cytarabine therapy. No
      differences were found in the rates of leukemic regrowth, CR, or infectious
      complications in either arm. Of 205 patients who achieved CR, 169 were medically
      well and were randomized to receive cytarabine alone or a combination of
      cytarabine and mitoxantrone. With a median follow-up of 7.7 years, the median
      disease-free survival times were 11 months and 10 months for those randomized to
      cytarabine or cytarabine/mitoxantrone, respectively. Rates of relapse, excluding
      deaths in CR, were 77% for cytarabine and 82% for cytarabine/mitoxantrone.
      Induction randomization had no effect on leukemic relapse rate or remission
      duration in either postremission arm. Because cytarabine/mitoxantrone was more
      toxic and no more effective than cytarabine, it was concluded that this higher
      dose therapy had no benefit in the postremission management of older patients
      with de novo AML. These results suggest the need to develop novel therapeutic
      strategies for these patients. (Blood. 2001;98:548-553)

PMID- 11468149
TI  - Simultaneous fetal cell identification and diagnosis by epsilon-globin chain
      immunophenotyping and chromosomal fluorescence in situ hybridization.
AB  - Isolating fetal erythroblasts from maternal blood offers a promising noninvasive
      alternative for prenatal diagnosis. The current immunoenzymatic methods of
      identifying fetal cells from background maternal cells postenrichment by labeling
      gamma-globin are problematic. They are nonspecific because maternal cells may
      produce gamma-globin, give poor hybridization efficiencies with chromosomal
      fluorescence in situ hybridization (FISH), and do not permit simultaneous
      visualization of the fetal cell identifier and the FISH signal. We describe a
      novel technique that allows simultaneous visualization of fetal erythroblast
      morphology, chromosomal FISH, and epsilon-globin labeled with AMCA (7-amino-4
      methylcoumarin-3-acetic acid). AMCA was chosen as the fluorescent label to
      circumvent the problem of heme autofluorescence because the mean difference in
      relative fluorescence intensity between fetal erythroblasts stained positive for
      antiglobin antibody and autofluorescence of unstained cells was greater with AMCA
      (mean 43.2; 95% confidence interval [CI], 34.6-51.9; SD = 14.0) as the reporting
      label compared with fluorescein isothiocyanate (mean 24.2; 95% CI, 16.4-31.9; SD
      = 12.4) or phycoerythrin (mean 9.8; 95% CI, 4.8-14.8; SD = 8.0). Median FISH
      hybridization efficiency was 97%, comparable to the 98% (n = 5 paired samples)
      using Carnoy fixative. One epsilon-positive fetal erythroblast was identified
      among 10(5) maternal nucleated cells in 6 paired mixture experiments of fetal
      erythroblasts in maternal blood (P <.001). Male epsilon-positive fetal
      erythroblasts were clearly distinguishable from adult female epsilon-negative
      erythroblasts, with no false positives (n = 1000). The frequency of fetal
      erythroblasts expressing epsilon-globin declines linearly from 7 to 14 weeks'
      gestation (y = -15.8 x + 230.8; R(2) = 0.8; P <.001). We describe a rapid and
      accurate method to detect simultaneously fetal erythroblast morphology,
      intracytoplasmic epsilon-globin, and nuclear FISH. (Blood. 2001;98:554-557)

PMID- 11468150
TI  - Origins of "late" relapse in childhood acute lymphoblastic leukemia with TEL-AML1
      fusion genes.
AB  - Approximately 20% of childhood B-precursor acute lymphoblastic leukemia (ALL) has
      a TEL-AML1 fusion gene, often in association with deletions of the nonrearranged
      TEL allele. TEL-AML1 gene fusion appears to be an initiating event and usually
      occurs before birth, in utero. This subgroup of ALL generally presents with low-
      or medium-risk features and overall has a very good prognosis. Some patients,
      however, do have relapses late or after the cessation of treatment, at least on
      some therapeutic protocols. They usually achieve sustained second remissions.
      Posttreatment relapses, or even very late relapses (5-20 years after diagnosis),
      in childhood ALL are clonally related to the leukemic cells at diagnosis (by IGH
      or T-cell receptor [TCR] gene sequencing) and are considered, therefore, to
      represent a slow re-emergence or escape of the initial clone seen at diagnosis.
      Microsatellite markers and fluorescence in situ hybridization identified
      deletions of the unrearranged TEL allele and IGH/TCR gene rearrangements were
      analyzed; the results show that posttreatment relapse cells in 2 patients with
      TEL-AML1-positive ALL were not derived from the dominant clone present at
      diagnosis but were from a sibling clone. In contrast, a patient who had a relapse
      while on treatment with TEL-AML1 fusion had essentially the same TEL deletion,
      though with evidence for microsatellite instability 5(') of TEL gene deletion at
      diagnosis, leading to extended 5(') deletion at relapse. It is speculated that,
      in some patients, combination chemotherapy for childhood ALL may fail to
      eliminate a fetal preleukemic clone with TEL-AML1 and that a second, independent
      transformation event within this clone after treatment gives rise to a new
      leukemia masquerading as relapse. (Blood. 2001;98:558-564)

PMID- 11468151
TI  - Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the
      conditioning regimen prior to stem cell transplantation for patients with high
      risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II
      study.
AB  - The conditioning regimen prior to stem cell transplantation in 36 patients with
      high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was
      intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal
      antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was
      observed in all cases. Radioimmunotherapy with the labeled antibody provided a
      mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal
      organ receiving the highest dose of supplemental radiation (mean 7.4 Gy).
      Radioimmunotherapy was followed by standard full-dose conditioning with total
      body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or
      without thiotepa. Patients subsequently received a T-cell-depleted allogeneic
      graft from a HLA-identical family donor (n = 15) or an alternative donor (n =
      17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft
      was used. Infusion-related toxicity due to the labeled antibody was minimal, and
      no increase in treatment-related mortality due to the radioimmunoconjugate was
      observed. Day +30 and day +100 mortalities were 3% and 6%, respectively, and
      after a median follow-up of 18 months treatment-related mortality was 22%. Late
      renal toxicity was observed in 17% of patients. The relapse rate of 15 patients
      undergoing transplantation in first CR (complete remission) or second CR was 20%;
      21 patients not in remission at the time of transplantation had a 30% relapse
      rate. (Blood. 2001;98:565-572)

PMID- 11468152
TI  - Parainfluenza virus infections after hematopoietic stem cell transplantation:
      risk factors, response to antiviral therapy, and effect on transplant outcome.
AB  - Parainfluenza virus (PIV) infections may be significant causes of morbidity and
      mortality in patients undergoing stem cell transplantation, but data regarding
      their impact on transplant-related mortality is limited. This study sought to
      determine the risk factors of PIV acquisition and progression to lower
      respiratory tract infection, their impact on transplant-related mortality, and
      the effectiveness of antiviral therapy. A total of 3577 recipients of
      hematopoietic stem cell transplantation (HSCT) between 1990 and 1999 were
      studied. PIV infections occurred in 253 patients (7.1%); 78% of these infections
      were community acquired. Multivariable analysis identified the receipt of an
      unrelated transplant as the only risk factor for PIV acquisition; the dose of
      corticosteroids at the time of PIV infection acquisition was the primary factor
      associated with the development of PIV-3 pneumonia, both among allogeneic and
      autologous HSCT recipients. Both PIV-3 upper respiratory infection and pneumonia
      were associated with overall mortality. Pulmonary copathogens were isolated from
      29 patients (53%) with pneumonia. Mortality was highly influenced by the presence
      of copathogens and the need for mechanical ventilation. Aerosolized ribavirin
      with or without intravenous immunoglobulin did not appear to alter mortality from
      PIV-3 pneumonia, nor did such therapy decrease the duration of viral shedding
      from the nasopharynx among patients with pneumonia. Corticosteroid administration
      thus drives the development of PIV pneumonia in a dose-dependent fashion, even
      among autologous HSCT recipients. Both upper and lower tract PIV infections are
      predictors of mortality after HSCT. Currently available antiviral therapy appears
      to be inadequate in reducing viral shedding or mortality once pneumonia is
      established. (Blood. 2001;98:573-578)

PMID- 11468153
TI  - Early lymphocyte recovery predicts superior survival after autologous
      hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin
      lymphoma.
AB  - Autologous stem cell transplantation (ASCT) improves survival in patients with
      previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive,
      aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic
      stem cell transplantation have been related to early absolute lymphocyte count
      (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the
      relation between ALC recovery and clinical outcomes in MM and NHL was not
      previously described. This is a retrospective study of patients with MM and NHL
      who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold
      was determined at 500 cells/microL on day 15 after ASCT. The study identified 126
      patients with MM and 104 patients with NHL. The median overall survival (OS) and
      progression-free survival (PFS) times for patients with MM were significantly
      longer in patients with an ALC of 500 cells/microL or more than patients with an
      ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P
      <.0003, respectively). For patients with NHL, the median OS and PFS times were
      significantly longer in patients with an ALC of 500 cells/microL or more versus
      those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not
      reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated
      day 15 ALC to be an independent prognostic indicator for OS and PFS rates for
      both groups of patients. In conclusion, ALC is correlated with clinical outcome
      and requires further study. (Blood. 2001;98:579-585)

PMID- 11468154
TI  - Myeloablation and autologous peripheral blood stem cell rescue results in
      hematologic and clinical responses in patients with myeloid metaplasia with
      myelofibrosis.
AB  - Current therapeutic options for myeloid metaplasia with myelofibrosis (MMM) are
      limited. A pilot study was conducted of autologous peripheral blood stem cell
      (PBSC) collection in 27, followed by transplantation in 21 patients with MMM. The
      median age was 59 (range 45-75) years. PBSCs were mobilized at steady state (n =
      2), after granulocyte colony-stimulating factor (G-CSF) alone (n = 17), or after
      anthracycline-cytarabine induction plus G-CSF (n = 8). A median of 11.6 x 10(6)
      (range 0 to 410 x 10(6)) CD34(+) cells per kilogram were collected. Twenty-one
      patients then underwent myeloablation with oral busulfan (16 mg/kg) and PBSC
      transplantation. The median times to neutrophil and platelet recovery after
      transplantation were 21 (range 10-96) and 21 (range, 13 to > or = 246) days,
      respectively. Five patients received back-up PBSC infusion because of delayed
      neutrophil or platelet recovery. The median follow-up is 390 (range 70-1623) days
      after transplantation, and the 2-year actuarial survival is 61%. After
      transplantion, 6 patients died: 3 of nonrelapse causes (1 within 100 days of PBSC
      infusion) and 3 of disease progression. Erythroid response (hemoglobin > or = 100
      g/L [10 gm/dL] without transfusion for > or = 8 weeks) occurred in 10 of 17
      anemic patients. Four of 8 patients with a platelet count less than 100 x 10(9)/L
      (100 000/microL) responded with a durable platelet count more than 100 x 10(9)/L
      (100 000/microL). Symptomatic splenomegaly improved in 7 of 10 patients. It is
      concluded that (1) PBSC collection was feasible and stable engraftment occurred
      after transplantation in most patients with MMM, (2) myeloablation with busulfan
      was associated with acceptable toxicity, (3) a significant proportion of patients
      derived clinical benefit after treatment, and (4) further investigation of this
      novel approach is warranted. (Blood. 2001;98:586-593)

PMID- 11468155
TI  - Lentivirus administration to rat muscle provides efficient sustained expression
      of erythropoietin.
AB  - A lentivirus pseudotyped with vesicular stomatitis virus G protein (VSV-G)
      encoding rat erythropoietin (EPO) complementary DNA was administered to rat
      skeletal muscle and red blood cell production was serially monitored. After a
      single intramuscular injection hematocrit values increased and reached a plateau
      at about 35 days and were sustained for at least 14 months. Virus doses of 6 x
      10(7) infectious units and 6 x 10(6) infectious units produced significantly
      increased mean hematocrit values of 68.5% +/- 2.1% (P <.001, n = 4) and 52.7% +/-
      1.3% (P <.001, n = 3), respectively, over values of control animals receiving
      normal saline (46.2% +/- 1.5%, n = 2). A polymerase chain reaction (PCR) assay
      for vector sequences in genomic DNA showed muscle tissue at the site of injection
      was positive and undetectable in liver, spleen, kidney, and lung. The
      intramuscular administration of lentivirus provided a dose-responsive, highly
      efficient and sustained EPO gene delivery, suggesting these vectors may be
      applied generally to the systemic delivery of proteins such as hormones and
      clotting factors. (Blood. 2001;98:594-596)

PMID- 11468156
TI  - Transfer of the human telomerase reverse transcriptase (TERT) gene into T
      lymphocytes results in extension of replicative potential.
AB  - In most human somatic cells telomeres progressively shorten with each cell
      division eventually leading to chromosomal instability and cell senescence. The
      loss of telomere repeats with cell divisions may also limit the replicative life
      span of antigen-specific T lymphocytes. Recent studies have shown that the
      replicative life span of various primary human cells can be prolonged by induced
      expression of the telomerase reverse transcriptase (hTERT) gene. To test whether
      introduction of hTERT can extend the life span of primary human T lymphocytes,
      naive CD8(+) T lymphocytes were transfected with retroviral vectors containing
      the hTERT gene. Transduced T-cell clones expressed high levels of telomerase and
      either maintained or elongated their telomere lengths upon culture for extended
      periods of time. Two of the transduced subclones retained a normal cloning
      efficiency for more than 170 population doublings (PDs). In contrast, T-cell
      clones transfected with control vectors exhibited progressive telomere length
      shortening and stopped proliferation at around 108 PDs. Telomerase-positive T
      clones had a normal 46,XY karyotype, maintained their cytotoxic properties, and
      showed very little staining for the apoptotic marker annexin-V. These results
      indicate that ectopic hTERT gene expression is capable of extending the
      replicative life span of primary human CD8(+) cytotoxic T lymphocytes. (Blood.
      2001;98:597-603)

PMID- 11468157
TI  - Gene transfer into murine hematopoietic stem cells with helper-free foamy virus
      vectors.
AB  - Gene transfer into hematopoietic stem cells (HSCs) is an ideal treatment strategy
      for many genetic and hematologic diseases. However, progress has been limited by
      the low HSC transduction rates obtained with retroviral vectors based on murine
      leukemia viruses. This study examined the potential of vectors derived from the
      nonpathogenic human foamy virus (HFV) to transduce human CD34(+) cells and murine
      HSCs. More than 80% of human hematopoietic progenitors present in CD34(+) cell
      preparations derived from cord blood were transduced by a single overnight
      exposure to HFV vector stocks. Mice that received transduced bone marrow cells
      expressed the vector-encoded transgene long term in all major hematopoietic cell
      lineages and in over 50% of cells in some animals. Secondary bone marrow
      transplants and integration site analysis confirmed that gene transfer occurred
      at the stem cell level. Transgene silencing was not observed. Thus vectors based
      on foamy viruses represent a promising approach for HSC gene therapy. (Blood.
      2001;98:604-609)

PMID- 11468158
TI  - Localization of distal regulatory domains in the megakaryocyte-specific platelet
      basic protein/platelet factor 4 gene locus.
AB  - The genes for the related human (h) chemokines, PBP (platelet basic protein) and
      PF4 (platelet factor 4), are within 5.3 kilobases (kb) of each other and form a
      megakaryocyte-specific gene locus. The hypothesis was considered that the PBP and
      PF4 genes share a common distal regulatory region(s) that leads to their high
      level megakaryocyte-specific expression in vivo. This study examined PBP and PF4
      expression in transgenic mice using 4 distinct human PBP/PF4 gene locus
      constructs. These studies showed that within the region studied there was
      sufficient information to regulate tissue-specific expression of both hPBP and
      hPF4. Indeed this region contained sufficient DNA information to lead to
      expression levels of PBP and PF4 comparable to the homologous mouse genes in a
      position-independent, copy number-dependent fashion. These studies also indicated
      that the DNA domains that led to this expression were distinct for the 2 genes;
      hPBP expression is regulated by a region that is 1.5 to 4.4 kb upstream of that
      gene. Expression of hPF4 is regulated by a region that is either intergenic
      between the 2 genes or immediately downstream of the hPF4 gene. Comparison of the
      available human and mouse sequences shows conserved flanking region domains
      containing potential megakaryocyte-related transcriptional factor DNA-binding
      sites. Further analysis of these regulatory regions may identify enhancer domains
      involved in megakaryopoiesis that may be useful in the selective expression of
      other genes in megakaryocytes and platelets as a strategy for regulating
      hemostasis, thrombosis, and inflammation. (Blood. 2001;98:610-617)

PMID- 11468159
TI  - The Hox cofactor and proto-oncogene Pbx1 is required for maintenance of
      definitive hematopoiesis in the fetal liver.
AB  - Pbx1 is the product of a proto-oncogene originally discovered at the site of
      chromosomal translocations in acute leukemias. It binds DNA as a complex with a
      broad subset of homeodomain proteins, but its contributions to hematopoiesis have
      not been established. This paper reports that Pbx1 is expressed in hematopoietic
      progenitors during murine embryonic development and that its absence results in
      severe anemia and embryonic lethality at embryonic day 15 (E15) or E16.
      Definitive myeloerythroid lineages are present in Pbx1(-/-) fetal livers, but the
      total numbers of colony-forming cells are substantially reduced. Fetal liver
      hypoplasia reflects quantitative as well as qualitative defects in the most
      primitive multilineage progenitors and their lineage-restricted progeny.
      Hematopoietic stem cells from Pbx1(-/-) embryos have reduced colony-forming
      activity and are unable to establish multilineage hematopoiesis in competitive
      reconstitution experiments. Common myeloid progenitors (CMPs), the earliest known
      myeloerythroid-restricted progenitors, are markedly depleted in Pbx1(-/-) embryos
      at E14 and display clonogenic defects in erythroid colony formation. Comparative
      cell-cycle indexes suggest that these defects result largely from insufficient
      proliferation. Megakaryocyte- and erythrocyte-committed progenitors are also
      reduced in number and show decreased erythroid colony-forming potential. Taken
      together, these data indicate that Pbx1 is essential for the function of
      hematopoietic progenitors with erythropoietic potential and that its loss creates
      a proliferative constriction at the level of the CMP. Thus, Pbx1 is required for
      the maintenance, but not the initiation, of definitive hematopoiesis and
      contributes to the mitotic amplifications of progenitor subsets through which
      mature erythrocytes are generated. (Blood. 2001;98:618-626)

PMID- 11468160
TI  - Fetal liver myelopoiesis occurs through distinct, prospectively isolatable
      progenitor subsets.
AB  - Hematopoietic fate maps in the developing mouse embryo remain imprecise.
      Definitive, adult-type hematopoiesis first appears in the fetal liver, then
      progresses to the spleen and bone marrow. Clonogenic common lymphoid progenitors
      and clonogenic common myeloid progenitors (CMPs) in adult mouse bone marrow that
      give rise to all lymphoid and myeloid lineages, respectively, have recently been
      identified. Here it is shown that myelopoiesis in the fetal liver similarly
      proceeds through a CMP equivalent. Fetal liver CMPs give rise to megakaryocyte
      erythrocyte-restricted progenitors (MEPs) and granulocyte-monocyte-restricted
      progenitors (GMPs) that can also be prospectively isolated by cell surface
      phenotype. MEPs and GMPs generate mutually exclusive cell types in clonogenic
      colony assays and in transplantation experiments, suggesting that the lineage
      restriction observed within each progenitor subset is absolute under normal
      conditions. Purified progenitor populations were used to analyze expression
      profiles of various hematopoiesis-related genes. Expression patterns closely
      matched those of the adult counterpart populations. These results suggest that
      adult hematopoietic hierarchies are determined early in the development of the
      definitive immune system and suggest that the molecular mechanisms underlying
      cell fate decisions within the myeloerythroid lineages are conserved from embryo
      to adult. (Blood. 2001;98:627-635)

PMID- 11468161
TI  - DUB-2A, a new member of the DUB subfamily of hematopoietic deubiquitinating
      enzymes.
AB  - Protein ubiquitination is an important regulator of cytokine-activated signal
      transduction pathways and hematopoietic cell growth. Protein ubiquitination is
      controlled by the coordinate action of ubiquitin-conjugating enzymes and
      deubiquitinating enzymes. Recently a novel family of genes encoding growth
      regulatory deubiquitinating enzymes (DUB-1 and DUB-2) has been identified. DUBs
      are immediate-early genes and are induced rapidly and transiently in response to
      cytokine stimuli. By means of polymerase chain reaction amplification with
      degenerate primers for the DUB-2 complementary DNA, 3 murine bacterial artificial
      chromosome (BAC) clones that contain DUB gene sequences were isolated. One BAC
      contained a novel DUB gene (DUB-2A) with extensive homology to DUB-2. Like DUB-1
      and DUB-2, the DUB-2A gene consists of 2 exons. The predicted DUB-2A protein is
      highly related to other DUBs throughout the primary amino acid sequence, with a
      hypervariable region at its C-terminus. In vitro, DUB-2A had functional
      deubiquitinating activity; mutation of its conserved amino acid residues
      abolished this activity. The 5' flanking sequence of the DUB-2A gene has a
      hematopoietic-specific functional enhancer sequence. It is proposed that there
      are at least 3 members of the DUB subfamily (DUB-1, DUB-2, and DUB-2A) and that
      different hematopoietic cytokines induce specific DUB genes, thereby initiating a
      cytokine-specific growth response. (Blood. 2001;98:636-642)

PMID- 11468162
TI  - Myelopoiesis in the zebrafish, Danio rerio.
AB  - Genome-wide chemical mutagenesis screens in the zebrafish (Danio rerio) have led
      to the identification of novel genes affecting vertebrate erythropoiesis. In
      determining if this approach could also be used to clarify the molecular genetics
      of myelopoiesis, it was found that the developmental hierarchy of myeloid
      precursors in the zebrafish kidney is similar to that in human bone marrow.
      Zebrafish neutrophils resembled human neutrophils, possessing segmented nuclei
      and myeloperoxidase-positive cytoplasmic granules. The zebrafish homologue of the
      human myeloperoxidase (MPO) gene, which is specific to cells of the neutrophil
      lineage, was cloned and used to synthesize antisense RNA probes for in situ
      hybridization analyses of zebrafish embryos. Granulocytic cells expressing
      zebrafish mpo were first evident at 18 hours after fertilization (hpf) in the
      posterior intermediate cell mass (ICM) and on the anterior yolk sac by 20 hpf. By
      24 hpf, mpo-expressing cells were observed along the ICM and within the
      developing vascular system. Thus, the mpo gene should provide a useful molecular
      probe for identifying zebrafish mutants with defects in granulopoiesis. The
      expression of zebrafish homologues was also examined in 2 other mammalian
      hematopoietic genes, Pu.1, which appears to initiate a commitment step in normal
      mammalian myeloid development, and L-Plastin, a gene expressed by human monocytes
      and macrophages. The results demonstrate a high level of conservation of the
      spatio-temporal expression patterns of these genes between zebrafish and mammals.
      The morphologic and molecular genetic evidence presented here supports the
      zebrafish as an informative model system for the study of normal and aberrant
      human myelopoiesis. (Blood. 2001;98:643-651)

PMID- 11468163
TI  - Epitope mapping of inhibitory antibodies against platelet glycoprotein Ibalpha
      reveals interaction between the leucine-rich repeat N-terminal and C-terminal
      flanking domains of glycoprotein Ibalpha.
AB  - The interaction of von Willebrand factor (vWF) with the platelet receptor
      glycoprotein Ibalpha (GPIbalpha) is important for platelet adhesion at high shear
      stress. Two functionally important antigenic areas within GPIbalpha were
      identified through the characterization of 5 new inhibitory anti-GPIb monoclonal
      antibodies (mAbs). The binding sites of 3 of these anti-GPIb mAbs, which were
      intercompeting and potently inhibiting shear stress-induced binding of vWF, were
      mapped within the N-terminal amino acid (aa) 1-59 area by the use of canine-human
      chimeras. These antibodies, however, had little or no effect (approximately 40%
      inhibition) on the binding of vWF induced by either botrocetin or ristocetin. On
      the other hand, the anti-GPIb mAbs 24G10 and 6B4, which blocked GPIb-vWF binding
      under all conditions examined, bound to 2 different regions of GPIbalpha, aa 1-81
      and aa 201-268, respectively. The epitope for 6B4 was further narrowed by phage
      display revealing 2 sets of peptide sequences aligning within aa 259-262 and aa
      230-242. In the latter region of GPIbalpha, the gain-of-function platelet-type
      von Willebrand disease (PT-vWD) mutations have been identified. Alignment was
      partially confirmed because the binding of 6B4 to recombinant GPIbalpha fragments
      carrying either one of the PT-vWD mutations was considerably impaired but not
      completely abolished. In contrast, mAb 24G10 bound more strongly to mutant PT-vWD
      GPIbalpha. However, although 24G10 competed with 6B4 for binding to platelets, it
      bound to an epitope within aa 1-81 of GPIbalpha. In conclusion, 2 functionally
      important areas within GPIbalpha were identified: one localized within the
      leucine-rich repeat N-terminal aa 1-59 area and one composed of residues aa 1-81
      in close contact with aa 201-268. Moreover, further support is provided for the
      existence of an intramolecular interaction between the N-terminal flanking (aa 1
      81) and C-terminal flanking (aa 201-268) regions. (Blood. 2001;98:652-660)

PMID- 11468164
TI  - The impaired polymerization of fibrinogen Longmont (Bbeta166Arg-->Cys) is not
      improved by removal of disulfide-linked dimers from a mixture of dimers and
      cysteine-linked monomers.
AB  - This study identified a new substitution in the Bbeta chain of an abnormal
      fibrinogen, denoted Longmont, where the residue Arg166 was changed to Cys. The
      variant was discovered in a young woman with an episode of severe hemorrhage at
      childbirth and a subsequent mild bleeding disorder. The neo-Cys residues were
      always found to be disulfide-bridged to either an isolated Cys amino acid or to
      the corresponding Cys residue of another abnormal fibrinogen molecule, forming
      dimers. Removing the dimeric molecules using gel filtration did not correct the
      fibrin polymerization defect. Fibrinogen Longmont had normal fibrinopeptide A and
      B release and a functional polymerization site "a." Thus, the sites "A" and "a"
      can interact to form protofibrils, as evidenced by dynamic light-scattering
      measurements. These protofibrils, however, were unable to associate in the normal
      manner of lateral aggregation, leading to abnormal clot formation, as shown by an
      impaired increase in turbidity. Therefore, it is concluded that the substitution
      of Arg166-->Cys-Cys alters fibrinogen Longmont polymerization by disrupting
      interactions that are critical for normal lateral association of protofibrils.
      (Blood. 2001;98:661-666)

PMID- 11468165
TI  - The p38 mitogen-activated protein kinase pathway plays a critical role in
      thrombin-induced endothelial chemokine production and leukocyte recruitment.
AB  - Thrombin, the terminal serine protease in the coagulation cascade, is a
      proinflammatory molecule in vivo and induces endothelial activation in vitro. The
      cellular signaling mechanisms involved in this function are unknown. The role of
      the p38 mitogen-activated protein kinase (MAPK) signaling pathway in thrombin
      induced chemokine production was studied. Phosphorylation of both p38 MAPK and
      its substrate, ATF-2, was observed in human umbilical vein endothelial cells
      (HUVECs) stimulated with thrombin, with a maximum after 5 minutes of stimulation.
      Using the selective p38 MAPK inhibitor SB203580, there was a significant decrease
      in thrombin-induced interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP
      1) protein production and messenger RNA steady-state levels. In addition,
      SB203580 decreased IL-8 and MCP-1 production induced by the thrombin receptor-1
      agonist peptide (TRAP), suggesting functional links between the thrombin G
      protein-coupled receptor and the p38 MAPK pathway. Furthermore, endothelial
      activation in the presence of SB203580 decreased the chemotactic activity of
      thrombin-stimulated HUVEC supernatant on neutrophils and monocytic cells. In
      contrast, the p42/p44 MAPK pathway did not appear to be involved in thrombin- or
      TRAP-induced endothelial chemokine production, because there was no reduction in
      the presence of the p42/p44-specific inhibitor PD98059. These results demonstrate
      that the p38 rather than p42/44 MAPK signaling pathway plays an important role in
      thrombin-induced endothelial proinflammatory activation and suggest that
      inhibition of p38 MAPK may be an interesting target for anti-inflammatory
      strategies in vascular diseases combining thrombosis and inflammation. (Blood.
      2001;98:667-673)

PMID- 11468166
TI  - Aberrant dimerization of von Willebrand factor as the result of mutations in the
      carboxy-terminal region: identification of 3 mutations in members of 3 different
      families with type 2A (phenotype IID) von Willebrand disease.
AB  - The 3' end of the VWF gene was screened in the affected members of 3 different
      families with type 2A (phenotype IID) von Willebrand disease (vWD). Exons 49 to
      52 of the VWF gene were amplified and screened for mutations by chemical cleavage
      mismatch detection. Mismatched bands were detected in exon 52 of 2 patients and
      in exon 51 of a third patient. Using direct DNA sequencing, a heterozygous G8562A
      transition leading to a Cys2008Tyr substitution was found in all the patients in
      family 1, and a T8561A transversion leading to a Cys2008Ser substitution was
      found in both patients from family 2. In a patient from a third family, an 8-base
      deletion from nucleotide 8437 to 8444 was identified in exon 51. The 2 mutations
      in exon 52 were reproduced by in vitro site-directed mutagenesis of full-length
      von Willebrand factor (vWF) cDNA and transiently expressed in COS-7 cells. The
      corresponding recombinant VWFs for these 2 mutations exhibited the typical
      aberrant vWF:Ag multimer pattern seen in the plasma of the patients. These 3
      mutations demonstrate the importance of other carboxy-terminal cysteines in
      addition to the reported Cys2010 residue, in the normal dimerization of vWF, and
      their essential role in the assembly of normal multimeric vWF. (Blood.
      2001;98:674-680)

PMID- 11468167
TI  - Interaction of calmodulin with the cytoplasmic domain of the platelet membrane
      glycoprotein Ib-IX-V complex.
AB  - Engagement of platelet membrane glycoprotein (GP) Ib-IX-V by von Willebrand
      factor triggers Ca(++)-dependent activation of alphaIIbbeta3, resulting in
      (patho)physiological thrombus formation. It is demonstrated here that the
      cytoplasmic domain of GPIb-IX-V associates with cytosolic calmodulin. First, an
      anti-GPIbalpha antibody coimmunoprecipitated GPIb-IX and calmodulin from platelet
      lysates. Following platelet stimulation, calmodulin dissociated from GPIb-IX and,
      like the GPIb-IX-associated proteins 14-3-3zeta and p85, redistributed to the
      activated cytoskeleton. Second, a synthetic peptide based on the cytoplasmic
      sequence of GPIbbeta, R149-L167 (single-letter amino acid codes), affinity
      isolated calmodulin from platelet cytosol in the presence of Ca(++) as confirmed
      by comigration with bovine calmodulin on sodium dodecyl sulfate-polyacrylamide
      gels, by sequence analysis, and by immunoreactivity with the use of an
      anticalmodulin antibody. The membrane-proximal GPIbbeta sequence was analogous to
      a previously reported calmodulin-binding sequence in the leukocyte adhesion
      receptor, L-selectin. In addition, the cytoplasmic sequence of GPV, K529-G544,
      was analogous to a calmodulin-binding IQ motif within the alpha1c subunit of L
      type Ca(++) channels. Calmodulin coimmunoprecipitated with GPV from resting
      platelet lysates, but was dissociated in stimulated platelets. A GPV-related
      synthetic peptide also bound calmodulin and induced a Ca(++)-dependent shift on
      nondenaturing gels. Together, these results suggest separate regions of GPIb-IX-V
      can directly bind calmodulin, and this novel interaction potentially regulates
      aspects of GPIb-IX-V-dependent platelet activation. (Blood. 2001;98:681-687)

PMID- 11468168
TI  - Transendothelial migration of lymphocytes across high endothelial venules into
      lymph nodes is affected by metalloproteinases.
AB  - The migration of lymphocytes from the bloodstream into lymph nodes (LNs) via high
      endothelial venules (HEVs) is a prerequisite for the detection of processed
      antigen on mature dendritic cells and the initiation of immune responses. The
      capture and arrest of lymphocytes from flowing blood is mediated by the multistep
      adhesion cascade, but the mechanisms that lymphocytes use to penetrate the
      endothelial lining and the basement membrane of HEVs are poorly understood.
      Matrix metalloproteinases (MMPs) control the metastatic spread of tumor cells by
      regulating the penetration blood vessel basement membranes. In this study,
      synthetic and natural inhibitors were used to determine the role of MMPs and MMP
      related enzymes in regulating lymphocyte extravasation in mice. Mice were treated
      systemically with the hydroxamate-based MMP inhibitor Ro 31-9790 and plasma
      monitored for effective levels of Ro 31-9790, which block shedding of L-selectin.
      The total numbers of lymphocytes recruited into LNs were not altered, but L
      selectin levels were higher in mice treated with Ro 31-9790. A reduced number of
      lymphocytes completed diapedesis and there was an increase in the number of
      lymphocytes in the endothelial cell lining, rather than the lumen or the basement
      membrane of HEVs. Lymphocyte migration and L-selectin expression in the spleen
      were not altered by Ro 31-9790 treatment. Two MMP inhibitors, TIMP1 and Ro 32
      1541, did not block L-selectin shedding and had no effect on lymphocyte migration
      across HEVs. These results suggest that metalloproteinase activity is required
      for lymphocyte transmigration across HEVs into LNs and provide evidence for the
      concept that metalloproteinases are important players in some forms of
      transendothelial migration. (Blood. 2001;98:688-695)

PMID- 11468169
TI  - Characterization of thymus-seeding precursor cells from mouse bone marrow.
AB  - The nature of the cells that seed the thymus of an irradiated recipient after
      intravenous (IV) transfer of bone marrow (BM) cells was investigated using 2
      approaches. First, direct entry of a small number of donor BM cells into the
      thymus was tracked using a Ly-5 marker. Second, secondary IV transfer of the
      seeded thymus cells into a secondary recipient was used as an assay for precursor
      activity. A range of cell types was found to enter the recipient thymus
      initially, including B-lineage cells and myeloid cells, but T precursors were
      undetectable by flow cytometry over the first few days. Although all cells
      initially entering the thymus proliferated, no sustained thymus reconstitution
      was seen until day 4, when recognizable T-lineage precursors began to appear. The
      secondary transfer assays revealed the presence of lymphoid precursors in the
      recipient thymus, including T, NKT, NK, and B precursor activity, with a notable
      early burst of B-lineage generative capacity. There was no evidence of sustained
      myeloid precursor or multipotent stem cell activity, even though these were seen
      if BM cells were injected directly into the recipient thymus rather than
      introduced into the bloodstream. It is concluded that even though many cell types
      may initially enter an irradiated thymus, the thymus acts as a sieve, allowing
      lymphoid precursors, but not multipotent stem cells, to seed the environmental
      niches that permit selected precursor cell development and thymus reconstitution.
      (Blood. 2001;98:696-704)

PMID- 11468170
TI  - Human natural killer cells with polyclonal lectin and immunoglobulinlike
      receptors develop from single hematopoietic stem cells with preferential
      expression of NKG2A and KIR2DL2/L3/S2.
AB  - The stage of progenitor maturation and factors that determine the fate and clonal
      acquisition of human natural killer (NK) cell receptors during development are
      unknown. To study human NK cell receptor ontogeny, umbilical cord blood
      CD34(+)/Lin(-)/CD38(-) cells were cultured with a murine fetal liver line
      (AFT024) and defined cytokines. In the absence of lymphocyte-stimulating
      cytokines or when contact with AFT024 was prohibited, NK cell progeny were killer
      immunoglobulinlike receptor (KIR) and CD94 lectin receptor negative. In contrast,
      efficient NK cell differentiation and receptor acquisition was dependent on
      direct contact of progenitors with AFT024 and the addition of interleukin-15 (IL
      15) or IL-2 but not IL-7. To address the question of whether receptor acquisition
      was determined at the stem cell level, single CD34(+)/Lin(-)/CD38(-) progenitors
      were studied. More than 400 single cell progeny were analyzed from cultures
      containing IL-15 or IL-2 and NK cells were always polyclonal, suggesting that
      receptor fate is determined beyond an uncommitted progenitor and that receptor
      negative NK cells acquire class I-recognizing receptors after lineage commitment.
      KIR2DL2/L3/S2 was expressed more than KIR2DL1/S1 or KIR3DL1, and NKG2A was the
      dominant CD94 receptor, independent of whether the stem cell source contained the
      respective major histocompatibility complex class I ligand, suggesting a
      nonrandom sequence of receptor acquisition. The conclusion is that NK receptor
      fate is determined after NK cell commitment, does not require stromal
      presentation of human class I alleles, and is clonally stable after expression
      but dynamic because new receptors are acquired over time. (Blood. 2001;98:705
      713)

PMID- 11468171
TI  - The tropism of organ involvement in primary systemic amyloidosis: contributions
      of Ig V(L) germ line gene use and clonal plasma cell burden.
AB  - Primary systemic amyloidosis (AL) is a protein conformation disorder in which
      monoclonal immunoglobulin light chains produced by clonal plasma cells are
      deposited as amyloid in the kidneys, heart, liver, or other organs. Why patients
      with AL present with amyloid disease that displays such organ tropism is unknown.
      This study tested the hypothesis that both the light-chain variable region (Ig
      V(L)) germ line genes used by AL clones and the plasma cell burden influenced AL
      organ tropism. To assess the renal tropism of some light chains, an in vitro
      renal mesangial cell model of amyloid formation was used. With reverse
      transcription-polymerase chain reaction, Ig V(L) genes were sequenced from 60 AL
      patients whose dominant involved organs were renal (52%), cardiac (25%), hepatic
      (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients
      with clones derived from the 6a V(lambdaVI) germ line gene were more likely to
      present with dominant renal involvement, whereas those with clones derived from
      the 1c, 2a2, and 3r V(lambda) genes were more likely to present with dominant
      cardiac and multisystem disease. Patients with V(kappa) clones were more likely
      to have dominant hepatic involvement and patients who met the Durie criteria for
      myeloma (38%, 23 of 60) were more likely to present with dominant cardiac
      involvement independent of germ line gene use. In the in vitro model, unlike all
      other AL light chains tested, lambdaVI light chains formed amyloid rapidly both
      with and without amyloid-enhancing factor. These data support the hypothesis that
      germ line gene use and plasma cell burden influence the organ tropism of AL.
      (Blood. 2001;98:714-720)

PMID- 11468172
TI  - High production of interferon gamma but not interleukin-2 by human T-lymphotropic
      virus type I-infected peripheral blood mononuclear cells.
AB  - The transactivator protein of human T-lymphotropic virus I (HTLV-I), Tax, has
      been associated with the up-regulation of several host cell genes, including
      interleukin 2 (IL-2), the IL-2 receptor-alpha (IL-2Ralpha) chain (CD25),
      interferon gamma (IFN-gamma), and tumor necrosis factor (TNF). It has been
      proposed that an IL-2/CD25 autocrine loop plays a part in maintaining the very
      high proviral loads often found in HTLV-I infection. Furthermore, abnormal
      production of inflammatory cytokines might contribute to the pathogenesis of the
      inflammatory diseases associated with HTLV-I infection. However, there has been
      no study of the expression of these genes in freshly isolated peripheral blood
      mononuclear cells (PBMCs) naturally infected with HTLV-I. In the present study,
      flow cytometry was used to determine which cytokines are produced by freshly
      isolated PBMCs that spontaneously express the HTLV-I Tax protein. Surprisingly,
      the results show that intracellular Tax expression is associated with rapid up
      regulation of IFN-gamma but not TNF or IL-2. A proportion of HTLV-I-infected
      cells express both IFN-gamma and the surface markers of effector memory cells.
      Such cells are capable of migration through peripheral tissues and could
      therefore contribute to the inflammation seen in diseases such as HTLV-I
      associated myelopathy/tropical spastic paraparesis. (Blood. 2001;98:721-726)

PMID- 11468173
TI  - Dermal and pulmonary inflammatory disease in E-selectin and P-selectin double
      null mice is reduced in triple-selectin-null mice.
AB  - In the initial phase of an inflammatory response, leukocytes marginate and roll
      along the endothelial surface as a result of adhesive interactions between
      molecules on the endothelial cells and leukocytes. To evaluate the role of the 3
      selectins (E, L, and P) in leukocyte rolling and emigration, a null mutation for
      L-selectin was introduced into previously described embryonic stem cells with
      null mutations in the genes for both E-selectin and P-selectin (E/P double
      mutants) to produce triple-selectin-null mice (E-selectin, L-selectin, and P
      selectin [E/L/P] triple mutants). Triple-selectin homozygous mutant mice are
      viable and fertile and only rarely develop the severe mucocutaneous infections or
      pulmonary inflammation characteristic of E/P double-mutant mice. Surface
      expression of L-selectin was undetectable in triple-mutant mice on fluorescence
      activated cell-sorter analysis of peripheral neutrophils. Pathological studies
      revealed moderate cervical lymphadenopathy and lymphoplasmacytic infiltrate, but
      these were less extensive than in E/P double-mutant mice. Neutrophil emigration
      during thioglycolate-induced peritonitis was significantly reduced at 4, 8, and
      24 hours (35%, 65%, and 46% of wild-type values, respectively). Intravital
      microscopy of the cremaster muscle revealed almost no rolling at times up to 6
      hours after exteriorization, with or without addition of tumor necrosis factor
      alpha. The small amount of residual rolling was dependent on alpha(4)-integrin.
      The occurrence of skin and pulmonary disease in E/P double-mutant mice but not
      E/L/P triple-mutant mice suggests that deficiency of L-selectin alters the
      inflammatory response in E/P mutants. (Blood. 2001;98:727-735)

PMID- 11468174
TI  - Type I interferons in combination with bacterial stimuli induce apoptosis of
      monocyte-derived dendritic cells.
AB  - Both type I interferons (IFNs) as well as lipopolysaccharide (LPS) individually
      compromise selected monocytic or dendritic cell (DC) functions. This study
      investigates the influence of these agents on the differentiation and the
      regulation of cell death of monocyte-derived DCs generated in the presence of
      granulocyte-macrophage colony-stimulating factor plus interleukin-4 (IL-4). It is
      reported that excessive apoptosis occurred rapidly in monocyte-derived DC
      cultures, if IFN-alpha or IFN-beta was added in combination with LPS or
      lipoteichoic acid (LTA). The small fraction of cells surviving in such cultures
      displayed a mature DC phenotype with expression of CD83, CD80, and CD86. IL-10
      was found in the supernatants of monocyte-derived DC cultures, if supplemented
      with LPS or IFN-alpha plus LPS but not in control cultures. When monocyte-derived
      DCs were generated in the presence of IFN-alpha without LPS, these cells
      displayed an immature DC phenotype with a reduction of cell recovery but no overt
      apoptosis. However, the addition of LPS, LTA, LPS plus IFN-gamma, or tumor
      necrosis factor alpha (TNF-alpha) plus prostaglandin E2 to such cells again
      resulted in the rapid induction of apoptosis in the majority of cells, together
      with a reduced production of IL-12 p70 and TNF-alpha. Together, these data
      indicate an exquisite sensitivity of monocyte-derived DCs to activation-induced
      cell death if generated in the presence of IFN-alpha, indicating the existence of
      an important mechanism of immunosuppression caused by IFN-alpha-inducing agents,
      such as viral or bacterial stimuli. (Blood. 2001;98:736-742)

PMID- 11468175
TI  - Modulation of T-cell activation by the glucocorticoid-induced leucine zipper
      factor via inhibition of nuclear factor kappaB.
AB  - Previously a novel gene was identified that encodes a glucocorticoid-induced
      leucine zipper (GILZ) whose expression is up-regulated by dexamethasone. This
      study analyzed the role of GILZ in the control of T-cell activation and its
      possible interaction with nuclear factor kappaB (NF-kappaB). Results indicate
      that GILZ inhibits both T-cell receptor (TCR)-induced interleukin-2/interleukin-2
      receptor expression and NF-kappaB activity. In particular, GILZ inhibits NF
      kappaB nuclear translocation and DNA binding due to a direct protein-to-protein
      interaction of GILZ with the NF-kappaB subunits. Moreover, GILZ-mediated
      modulation of TCR-induced responses is part of a circuit because TCR triggering
      down-regulates GILZ expression. These results identify a new molecular mechanism
      involved in the dexamethasone-induced regulation of NF-kappaB activity and T-cell
      activation. (Blood. 2001;98:743-753)

PMID- 11468176
TI  - Differentiation of cytomegalovirus-specific CD8(+) T cells in healthy and
      immunosuppressed virus carriers.
AB  - During immunosuppression, cytomegalovirus (CMV) can reactivate and cause serious
      clinical problems. Normally, abundant virus replication is suppressed by immune
      effector mechanisms. To study the interaction between CD8(+) T cells and
      persisting viruses, frequencies and phenotypes of CMV-specific CD8(+) T cells
      were determined in healthy individuals and compared to those in renal transplant
      recipients. In healthy donors, function of circulating virus-specific CD8(+) T
      cells, as measured by peptide-induced interferon gamma (IFN-gamma) production,
      but not the number of virus-specific T cells enumerated by binding of specific
      tetrameric peptide/HLA complexes, correlated with the number of CMV-specific IFN
      gamma-secreting CD4(+) helper T cells. Circulating CMV- specific CD8(+) T cells
      did not express CCR7 and may therefore not be able to recirculate through
      peripheral lymph nodes. Based on coexpression of CD27 and CD45R0 most CMV
      specific T cells in healthy donors appeared to be memory-type cells. Remarkably,
      frequencies of CMV-specific CD8(+) T cells were significantly higher in
      immunosuppressed individuals than in healthy donors. In these patients CMV
      specific cells predominantly had an effector phenotype, that is, CD45R0(+)CD27(
      )CCR7(-) or CD45RA(+)CD27(-)CCR7(-) and contained both granzyme B and perforin.
      Our data show that in response to immunosuppressive medication quantitative and
      qualitative changes occur in the CD8(+) T-cell compartment. These adaptations may
      be instrumental to maintain CMV latency. (Blood. 2001;98:754-761)

PMID- 11468177
TI  - STAT3 is constitutively activated in Hodgkin cell lines.
AB  - Hodgkin disease (HD) represents a malignant lymphoma in which the putative
      malignant Hodgkin and Reed-Sternberg cells are rare and surrounded by abundant
      reactive nonmalignant cells. It has been suggested that cytokines such as
      interleukin-6 (IL-6) are involved in the pathogenesis of the disease. The
      expression of the IL-6 receptor (IL-6R) complex and its link to the activation of
      signal transducers and activators of transcription (STAT) molecules in HD cell
      lines was investigated. Gel retardation and Western blot analyses revealed a high
      level of constitutively activated STAT3 in 5 of 7 HD cell lines, which could not
      be detected in Burkitt lymphoma cell lines. Different levels of IL-6R protein
      were measured in various HD cell lines: L428 and Dev cells were characterized by
      very low levels of gp80 and gp130, on KMH2 cells only gp130 but no gp80 was
      detected, whereas L540, L591, HDLM2, and L1236 were positive for both gp80 and
      gp130, suggesting a possible autocrine stimulation of STAT3. However, a further
      increase in STAT3 activation on IL-6 or IL-6/soluble IL-6R stimulation was not
      observed. Neutralizing monoclonal antibodies against IL-6, gp80, gp130, or both
      receptor subunits did not affect the proliferation or the constitutive activation
      of STAT molecules in HD cell lines. However, the tyrosine kinase inhibitor AG490
      blocked the constitutive activation of STAT3 and inhibited spontaneous growth of
      HD tumor cells. The evidence suggests abnormal STAT signaling and growth
      regulation in Hodgkin cell lines. (Blood. 2001;98:762-770)

PMID- 11468178
TI  - Identifying intercellular signaling genes expressed in malignant plasma cells by
      using complementary DNA arrays.
AB  - In multiple myeloma (MM), the growth of primary plasma cells depends not only on
      interleukin-6 (IL-6), but also on additional unidentified signals delivered by
      the bone marrow environment. Using Atlas complementary DNA (cDNA) arrays
      comprising 268 genes coding for intercellular signaling molecules, this study
      identified genes that are overexpressed in myeloma cells compared to autologous B
      lymphoblastoid cell lines. These genes encode the oncogenic Tyro3 tyrosine kinase
      receptor, the heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      that is an epithelial autocrine tumor growth factor, the thrombin receptor (TR)
      that is linked to HB-EGF and syndecan-1 processing and to cell invasion,
      chemokine receptors CCR1 and CCR2, the Wnt pathway actor Frizzled-related protein
      (FRZB), and the Notch receptor ligand Jagged 2. These data, obtained with the
      Atlas cDNA array, were confirmed by reverse transcriptase-polymerase chain
      reaction or protein analysis or both. Furthermore, Tyro3, HB-EGF, TR, and FRZB
      gene expression was documented in purified primary malignant plasma cells from
      patients with plasma cell leukemia or MM. HB-EGF and FRZB were poorly expressed
      in purified polyclonal plasma cells. Finally, HB-EGF was proved to be an
      essential autocrine growth factor for the XG-1 myeloma cells. This study shows
      the potency and the biologic relevance of cDNA arrays used to analyze
      simultaneously a large panel of intercellular signaling genes and, by identifying
      several genes overexpressed in malignant plasma cells, opens new fields of
      investigation in MM biology. (Blood. 2001;98:771-780)

PMID- 11468179
TI  - Nodal marginal zone B-cell lymphomas may arise from different subsets of marginal
      zone B lymphocytes.
AB  - Nodal marginal zone B-cell lymphoma (MZL) is a rare and not extensively studied
      entity that accounts for approximately 2% of all non-Hodgkin lymphomas.
      Complementarity-determining regions 2 and 3 (CDR2, CDR3) of the immunoglobulin
      heavy-chain variable region (V(H)) genes were amplified by polymerase chain
      reaction (PCR), cloned, and sequenced in 8 patients with nodal MZL. All showed a
      potentially functional V(H) rearrangement. The use of V(H) gene families was
      unbiased and without overrepresentation of any particular V(H) gene or gene
      family. The presence of somatic V(H) mutations was detected, with a deviation
      from the closest germ line sequence ranging from 4% to 17% in 6 of 8 patients. In
      3 mutations, the replacement-to-silent mutation ratio suggested the presence of
      an antigen-selected process. Sequencing different subclones of the same cloned
      PCR products allowed the detection of intraclonal variability in 4 analyzed
      patients. The observed pattern of V(H) mutations suggested that nodal MZL,
      formerly deemed a malignancy of memory B cells, may arise from different subsets
      of marginal zone B cells-the naive B cells that express unmutated V(H) genes-from
      memory B cells showing somatic mutations without intraclonal variation, and from
      germinal center B cells defined by their capacity to undergo the somatic
      hypermutation process. (Blood. 2001;98:781-786)

PMID- 11468180
TI  - Altered apoptosis pathways in mantle cell lymphoma detected by oligonucleotide
      microarray.
AB  - An imbalance between cellular apoptosis and survival may be critical for the
      pathogenesis of lymphoma. Therefore, the gene expression pattern in lymph node
      preparations from patients with mantle cell lymphoma (MCL) was compared to the
      pattern in nonmalignant hyperplastic lymph nodes (HLs). Oligonucleotide
      microarray analysis was performed comparing 5 MCLs to 4 HLs using high-density
      microarrays. The expression data were analyzed using Genespring software. For
      confirmation, the expression of selected genes was analyzed by real-time
      polymerase chain reaction using the RNA extracted from 16 MCL and 12 HL samples.
      The focus was on 42 genes that were at least 3-fold down-regulated in MCL; in
      addition to the B-cell leukemia 2 (BCL2) system other apoptotic pathways were
      altered in MCL. The FAS-associated via death domain (FADD) gene that acts
      downstream of the FAS cascade as a key gene to induce apoptosis was more than 10
      fold down-regulated in MCL. Furthermore, the death-associated protein 6 (DAXX)
      gene, the caspase 2 (CASP2) gene, and the RIPK1 domain containing adapter with
      death domain (RAIDD) gene, which are key genes in other proapoptotic pathways,
      were also decreased in the MCL samples. The suggestion is made that in addition
      to the known overexpression of cyclin D1, which drives entry into the cell cycle,
      disturbances of pathways associated with apoptosis contribute to the development
      of MCL. (Blood. 2001;98:787-794)

PMID- 11468181
TI  - TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in
      multiple myeloma: therapeutic applications.
AB  - Multiple myeloma (MM) remains incurable and novel treatments are urgently needed.
      Preclinical in vitro and in vivo evaluations were performed to assess the
      potential therapeutic applications of human recombinant tumor necrosis factor
      (TNF)-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) in MM.
      TRAIL/Apo2L potently induced apoptosis of MM cells from patients and the majority
      of MM cell lines, including cells sensitive or resistant to dexamethasone (Dex),
      doxorubicin (Dox), melphalan, and mitoxantrone. TRAIL/Apo2L also overcame the
      survival effect of interleukin 6 on MM cells and did not affect the survival of
      peripheral blood and bone marrow mononuclear cells and purified B cells from
      healthy donors. The status of the TRAIL receptors (assessed by immunoblotting and
      flow cytometry) could not predict TRAIL sensitivity of MM cells. The anti-MM
      activity of TRAIL/Apo2L was confirmed in nu/xid/bg mice xenografted with human MM
      cells; TRAIL (500 microg intraperitoneally daily for 14 days) was well tolerated
      and significantly suppressed the growth of plasmacytomas. Dox up-regulated the
      expression of the TRAIL receptor death receptor 5 (DR5) and synergistically
      enhanced the effect of TRAIL not only against MM cells sensitive to, but also
      against those resistant to, Dex- or Dox-induced apoptosis. Nuclear factor (NF)
      kappaB inhibitors, such as SN50 (a cell-permeable inhibitor of the nuclear
      translocation and transcriptional activity of NF-kappaB) or the proteasome
      inhibitor PS-341, enhanced the proapoptotic activity of TRAIL/Apo2L against TRAIL
      sensitive MM cells, whereas SN50 reversed the TRAIL resistance of ARH-77 and IM-9
      MM cells. Importantly, normal B lymphocytes were not sensitized to TRAIL by
      either Dox, SN50, or PS-341. These preclinical studies suggest that TRAIL/Apo2L
      can overcome conventional drug resistance and provide the basis for clinical
      trials of TRAIL-based treatment regimens to improve outcome in patients with MM.
      (Blood. 2001;98:795-804)

PMID- 11468182
TI  - Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma
      cells.
AB  - Multiple myeloma (MM) is a clonal B-cell malignancy characterized by slow-growing
      plasma cells in the bone marrow (BM). Patients with MM typically respond to
      initial chemotherapies; however, essentially all progress to a chemoresistant
      state. Factors that contribute to the chemorefractory phenotype include
      modulation of free radical scavenging, increased expression of drug efflux pumps,
      and changes in gene expression that allow escape from apoptotic signaling. Recent
      data indicate that arsenic trioxide (As(2)O(3)) induces remission of refractory
      acute promyelocytic leukemia and apoptosis of cell lines overexpressing Bcl-2
      family members; therefore, it was hypothesized that chemorefractory MM cells
      would be sensitive to As(2)O(3). As(2)O(3) induced apoptosis in 4 human MM cell
      lines: 8226/S, 8226/Dox40, U266, and U266/Bcl-x(L). The addition of interleukin-6
      had no effect on cell death. Glutathione (GSH) has been implicated as an
      inhibitor of As(2)O(3)-induced cell death either through conjugating As(2)O(3) or
      by sequestering reactive oxygen induced by As(2)O(3). Consistent with this
      possibility, increasing GSH levels with N-acetylcysteine attenuated As(2)O(3)
      cytotoxicity. Decreases in GSH have been associated with ascorbic acid (AA)
      metabolism. Clinically relevant doses of AA decreased GSH levels and potentiated
      As(2)O(3)-mediated cell death of all 4 MM cell lines. Similar results were
      obtained in freshly isolated human MM cells. In contrast, normal BM cells
      displayed little sensitivity to As(2)O(3) alone or in combination with AA.
      Together, these data suggest that As(2)O(3) and AA may be effective
      antineoplastic agents in refractory MM and that AA might be a useful adjuvant in
      GSH-sensitive therapies. (Blood. 2001;98:805-813)

PMID- 11468183
TI  - p53 dysfunction in B-cell chronic lymphocytic leukemia: inactivation of ATM as an
      alternative to TP53 mutation.
AB  - The well-established association between TP53 mutations and adverse clinical
      outcome in a range of human cancers reflects the importance of p53 protein in
      regulating tumor-cell growth and survival. Although it is theoretically possible
      for p53 dysfunction to arise through mechanisms that do not involve TP53
      mutation, such a phenomenon has not previously been demonstrated in a sporadic
      tumor. Here, we show that p53 dysfunction in B-cell chronic lymphocytic leukemia
      (CLL) can occur in the absence of TP53 mutation and that such dysfunction is
      associated with mutation of the gene encoding ATM, a kinase implicated in p53
      activation. Forty-three patients with CLL were examined for p53 dysfunction, as
      detected by impaired up-regulation of p53 and of the p53-dependent protein
      p21(CIP1/WAF1) after exposure to ionizing radiation (IR). Thirty (70%) patients
      had normal p53 responses and underwent progressive IR-induced apoptosis. In 13
      (30%) patients, p21 up-regulation was markedly impaired, indicating p53
      dysfunction. Six (14%) of these patients with p53 dysfunction had increased
      baseline levels of p53, were found to have TP53 mutations, and were completely
      resistant to IR-induced apoptosis. In the other 7 (16%) patients with p53
      dysfunction, IR-induced p53 up-regulation and apoptosis were markedly impaired,
      but baseline levels of p53 were not increased, and no TP53 mutations were
      detected. Each of these patients was found to have at least one ATM mutation, and
      a variable reduction in ATM protein was detected in all 4 patients examined. This
      is the first study to provide a direct demonstration that p53 dysfunction can
      arise in a sporadic tumor by a mechanism that does not involve TP53 mutation.
      (Blood. 2001;98:814-822)

PMID- 11468184
TI  - HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2
      requirement for proliferation of primary human peripheral blood mononuclear
      cells.
AB  - The p12(I) protein, encoded by the pX open reading frame I of the human T
      lymphotropic virus type 1 (HTLV-1), is a hydrophobic protein that localizes to
      the endoplasmic reticulum and the Golgi. Although p12(I) contains 4 minimal
      proline-rich, src homology 3-binding motifs (PXXP), a characteristic commonly
      found in proteins involved in signaling pathways, it has not been known whether
      p12(I) has a role in modulating intracellular signaling pathways. This study
      demonstrated that p12(I) binds to the cytoplasmic domain of the interleukin-2
      receptor (IL-2R) beta chain that is involved in the recruitment of the Jak1 and
      Jak3 kinases. As a result of this interaction, p12(I) increases signal
      transducers and activators of transcription 5 (STAT5) DNA binding and
      transcriptional activity and this effect depends on the presence of both IL-2R
      beta and gamma(c) chains and Jak3. Transduction of primary human peripheral blood
      mononuclear cells (PBMCs) with a human immunodeficiency virus type 1-based
      retroviral vector expressing p12(I) also resulted in increased STAT5
      phosphorylation and DNA binding. However, p12(I) could increase proliferation of
      human PBMCs only after stimulation of T-cell receptors by treatment of cells with
      low concentrations of alphaCD3 and alphaCD28 antibodies. In addition, the
      proliferative advantage of p12(I)-transduced PBMCs was evident mainly at low
      concentrations of IL-2. Together, these data indicate that p12(I) may confer a
      proliferative advantage on HTLV-1-infected cells in the presence of suboptimal
      antigen stimulation and that this event may account for the clonal proliferation
      of infected T cells in vivo. (Blood. 2001;98:823-829)

PMID- 11468185
TI  - Benzene metabolites antagonize etoposide-stabilized cleavable complexes of DNA
      topoisomerase IIalpha.
AB  - Chronic exposure to benzene is associated with hematotoxicity and acute
      myelogenous leukemia. Inhibition of topoisomerase IIalpha (topo II) has been
      implicated in the development of benzene-induced cytogenetic aberrations. The
      purpose of this study was to determine the mechanism of topo II inhibition by
      benzene metabolites. In a DNA cleavage/relaxation assay, topo II was inhibited by
      p-benzoquinone and hydroquinone at 10 microM and 10 mM, respectively. On
      peroxidase activation, inhibition was seen with 4,4'-biphenol, hydroquinone, and
      catechol at 10 microM, 10 microM, and 30 microM, respectively. But, in no case
      was cleavable complex stabilization observed and the metabolites appeared to act
      at an earlier step of the enzyme cycle. In support of this conclusion, several
      metabolites antagonized etoposide-stabilized cleavable complex formation and
      inhibited topo II-DNA binding. It is therefore unlikely that benzene-induced
      acute myelogenous leukemia stems from events invoked for leukemogenic topo II
      cleavable complex-stabilizing antitumor agents. (Blood. 2001;98:830-833)

PMID- 11468186
TI  - DNA damage-induced cell-cycle arrest of hematopoietic cells is overridden by
      activation of the PI-3 kinase/Akt signaling pathway.
AB  - Exposure of hematopoietic cells to DNA-damaging agents induces cell-cycle arrest
      at G1 and G2/M checkpoints. Previously, it was shown that DNA damage-induced
      growth arrest of hematopoietic cells can be overridden by treatment with cytokine
      growth factors, such as erythropoietin (EPO) or interleukin-3 (IL-3). Here, the
      cytokine-activated signaling pathways required to override G1 and G2/M
      checkpoints induced by gamma-irradiation (gamma-IR) are characterized. Using
      factor-dependent myeloid cells stably expressing EPO receptor (EPO-R) mutants, it
      is shown that removal of a minimal domain required for PI-3K signaling abrogated
      the ability of EPO to override gamma-IR-induced cell-cycle arrest. Similarly, the
      ability of cytokines to override gamma-IR-induced arrest was abolished by an
      inhibitor of PI-3K (LY294002) or by overexpression of dominant-negative Akt.
      Moreover, the ability of EPO to override these checkpoints in cells expressing
      defective EPO-R mutants could be restored by overexpression of a constitutively
      active Akt. Thus, activation of a PI-3K/Akt signaling pathway is required for
      cytokine-dependent suppression of DNA-damage induced checkpoints. Together, these
      findings suggest a novel role for PI-3K/Akt pathways in the modulation of growth
      arrest responses to DNA damage in hematopoietic cells. (Blood. 2001;98:834-841)

PMID- 11468187
TI  - The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as
      effective antiproliferative agents, IV: The mechanisms involved in inhibiting
      cell-cycle progression.
AB  - Some chelators of the pyridoxal isonicotinoyl hydrazone class have
      antiproliferative activity that is far greater than desferrioxamine (DFO). In
      this study, DFO was compared with one of the most active chelators (311) on the
      expression of molecules that play key roles in cell-cycle control. This was vital
      for understanding the role of iron (Fe) in cell-cycle progression and for
      designing chelators to treat cancer. Incubating cells with DFO, and especially
      311, resulted in a decrease in the hyperphosphorylated form of the retinoblastoma
      susceptibility gene product (pRb). Chelators also decreased cyclins D1, D2, and
      D3, which bind with cyclin-dependent kinase 4 (cdk4) to phosphorylate pRb. The
      levels of cdk2 also decreased after incubation with DFO, and especially 311,
      which may be important for explaining the decrease in hyperphosphorylated pRb.
      Cyclins A and B1 were also decreased after incubation with 311 and, to a lesser
      extent, DFO. In contrast, cyclin E levels increased. These effects were prevented
      by presaturating the chelators with Fe. In contrast to DFO and 311, the
      ribonucleotide reductase inhibitor hydroxyurea increased the expression of all
      cyclins. Hence, the effect of chelators on cyclin expression was not due to their
      ability to inhibit ribonucleotide reductase. Although chelators induced a marked
      increase in WAF1 and GADD45 mRNA transcripts, there was no appreciable increase
      in their protein levels. Failure to translate these cell-cycle inhibitors may
      contribute to dysregulation of the cell cycle after exposure to chelators.
      (Blood. 2001;98:842-850)

PMID- 11468188
TI  - The familial Mediterranean fever protein, pyrin, associates with microtubules and
      colocalizes with actin filaments.
AB  - Familial Mediterranean fever (FMF) is a recessive disorder characterized by
      episodes of fever and intense inflammation. FMF attacks are unique in their
      sensitivity to the microtubule inhibitor colchicine, contrasted with their
      refractoriness to the anti-inflammatory effects of glucocorticoids. The FMF gene,
      MEFV, was recently identified by positional cloning; it is expressed at high
      levels in granulocytes and monocytes. The present study investigated the
      subcellular localization of the normal gene product, pyrin. These experiments did
      not support previously proposed nuclear or Golgi localizations. Instead
      fluorescence microscopy demonstrated colocalization of full-length GFP- and
      epitope-tagged pyrin with microtubules; this was markedly accentuated in
      paclitaxel-treated cells. Moreover, immunoblot analysis of precipitates of
      stabilized microtubules with recombinant pyrin demonstrated a direct interaction
      in vitro. Pyrin expression did not affect the stability of microtubules. Deletion
      constructs showed that the unique N-terminal domain of pyrin is necessary and
      sufficient for colocalization, whereas disease-associated mutations in the C
      terminal B30.2 (rfp) domain did not disrupt this interaction. By phalloidin
      staining, a colocalization of pyrin with actin was also observed in perinuclear
      filaments and in peripheral lamellar ruffles. The proposal is made that pyrin
      regulates inflammatory responses at the level of leukocyte cytoskeletal
      organization and that the unique therapeutic effect of colchicine in FMF may be
      dependent on this interaction. (Blood. 2001;98:851-859)

PMID- 11468189
TI  - Characterization of the phosphatidylserine-exposing subpopulation of sickle
      cells.
AB  - Phosphatidylserine (PS), exclusively present in the inner monolayer of the normal
      red blood cell (RBC) membrane, is exposed in subpopulations of sickle cells. PS
      exposing RBCs were found predominantly among the densest and the very light
      sickle cells. Within the light RBC fraction, PS exposure was found on
      reticulocytes, transferrin receptor-expressing reticulocytes, and mature RBCs.
      The last subset contained low-density valinomycin-resistant RBCs, previously
      shown to have high Na(+) and low K(+) content. This subpopulation contained the
      highest percentage of PS-exposing cells. The PS-exposing sickle cells did not
      show the sustained high cytosolic Ca(++) levels that have been shown to activate
      scramblase activity. Data from this study indicate that PS exposure can occur at
      different stages in the life of the sickle RBC and that it correlates with the
      loss of aminophospholipid translocase activity, the only common denominator of
      the PS-exposing cells. The additional requirement of scramblase activation may
      occur during transient increases in cytosolic Ca(++). (Blood. 2001;98:860-867)

PMID- 11468190
TI  - Characterization of the T-cell repertoire in autologous graft-versus-host disease
      (GVHD): evidence for the involvement of antigen-driven T-cell response in the
      development of autologous GVHD.
AB  - Administration of cyclosporine A (CsA) after autologous stem cell transplantation
      elicits an autoimmune syndrome with pathology similar to graft-versus-host
      disease (GVHD). This syndrome, termed autologous GVHD, is associated with the
      appearance of autoreactive T cells directed at major histocompatibility class
      (MHC) class II antigens. In the rat model of autologous GVHD, clonal analysis
      reveals that the effector T cells are highly conserved and recognize a peptide
      from the invariant chain peptide presented by MHC class II. Although human
      autologous GVHD effector T cells share a similar phenotypic specificity,
      clonality of the response in humans has not been determined. To examine the human
      effector T-cell response, the T-cell repertoire of peripheral blood lymphocytes
      was assessed by complementarity-determining region 3 (CDR3) size distribution
      analysis and T-cell clonotype analysis in 26 patients treated with CsA after
      transplantation. Autologous GVHD developed in 3 of 4 patients with human
      leukocyte antigen (HLA)-DRB1*0701, and clonal expansions of beta-chain variable
      region (BV)16(+) T cells were shared. Clonal expansions within BV15(+) and
      BV22(+) T cells were also detected in 4 of 6 patients with HLA-DRB1*1501 and in 3
      of 4 patients with HLA-DRB1*0401, respectively. Sequencing of BV16 cDNA for which
      the CDR3 size pattern exhibited apparent clone predominance revealed an identical
      CDR3 peptide sequence in 2 different patients, one with HLA-DRB1*0701 and the
      other with HLA-DRB1*1502. These findings indicate that the discrete antigen
      driven expansion of T cells is involved in autologous GVHD. (Blood. 2001;98:868
      876)

PMID- 11468191
TI  - Defective expression of the interleukin-2/interleukin-15 receptor beta subunit
      leads to a natural killer cell-deficient form of severe combined
      immunodeficiency.
AB  - Development of T and natural killer (NK) cells is critically dependent on
      cytokine signaling, and defects in cytokine receptor complex subunits have been
      shown to result in severe combined immunodeficiency (SCID) syndromes in humans
      and in murine models. An infant boy had typical clinical features of SCID and was
      found to lack NK cells in his peripheral circulation. Molecular analysis did not
      reveal abnormalities in his gammac or JAK-3 genes, and he was investigated for
      defects in the interleukin-15 (IL-15) receptor complex because functional IL-15
      signaling is essential for NK cell development. Expression of the IL-2R/IL
      15Rbeta chain was significantly reduced in the patient's peripheral blood
      mononuclear cells (PBMCs) by immunoblot, flow cytometry, and Northern blot
      analysis. Furthermore, IL-2 stimulation of PBMCs showed only minimal tyrosine
      phosphorylation of JAK-3. These data demonstrate that defects in IL-2R/1L-15Rbeta
      expression can lead to a unique NK-deficient SCID immunophenotype. (Blood.
      2001;98:877-879)

PMID- 11468192
TI  - Association of the Q576R polymorphism in the interleukin-4 receptor alpha chain
      with indolent mastocytosis limited to the skin.
AB  - Gain-of-function mutations in c-kit, which appear to contribute to mast cell
      hyperplasia, have been detected in both limited and aggressive forms of
      mastocytosis, suggesting that other mutations or polymorphisms may contribute to
      the clinical phenotype. Because addition of interleukin-4 (IL-4) to mast cell
      cultures is reported to induce apoptosis, the hypothesis was considered that
      individuals carrying the gain-of-function polymorphism Q576R in the cytoplasmic
      domain of the alpha-subunit of the IL-4 receptor (IL-4R) might be relatively
      resistant to the gain-of-function mutation in c-kit. To assess this possibility,
      36 patients with either cutaneous or systemic mastocytosis were studied for
      association with the Q576R polymorphism. The Q576R polymorphism was found more
      frequently in those with disease limited to skin and who exhibited lower levels
      of surrogate disease markers. These data suggest that the Q576R IL-4R alpha-
      chain polymorphism may mitigate disease expression and confer a better prognosis
      in patients with mastocytosis. (Blood. 2001;98:880-882)

PMID- 11468193
TI  - Direct intracellular measurement of deoxygenated hemoglobin S solubility.
AB  - The solubility of deoxygenated hemoglobin S (HbS), which is the concentration of
      fully deoxygenated HbS in equilibrium with polymer (C(SAT)), is a factor that
      determines in vivo polymer formation. However, measurement of C(SAT) is usually
      performed under conditions that are far from physiological. In solution studies
      of HbS by Benesch et al, it was demonstrated that p50, the point at which
      hemoglobin is half-saturated with oxygen, is proportional to the amount of
      polymer formed and that it may be used to measure C(SAT). This method has been
      extended to measure C(SAT) in intact red cells by varying extracellular
      osmolarity, which, in turn, varies intracellular hemoglobin concentration. This
      method measures intracellular C(SAT) under physiological conditions with intact
      red cell contents and can be applied to human and transgenic mouse red cells. The
      principle is demonstrated by measuring p50 as a function of extracellular
      osmolarity for AA, SS, and AS red cells. (Blood. 2001;98:883-884)

PMID- 11468194
TI  - A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid
      leukemia blasts harboring FLT3 internal tandem duplication mutations.
AB  - Internal tandem duplication (ITD) mutations of the receptor tyrosine kinase FLT3
      have been found in 20% to 30% of patients with acute myeloid leukemia (AML).
      These mutations constitutively activate the receptor and appear to be associated
      with a poor prognosis. Recent evidence that this constitutive activation is
      leukemogenic renders this receptor a potential target for specific therapy. In
      this study, dose-response cytotoxic assays were performed with AG1295, a tyrosine
      kinase inhibitor active against FLT3, on primary blasts from patients with AML.
      For each patient sample, the degree of cytotoxicity induced by AG1295 was
      compared to the response to cytosine arabinoside (Ara C) and correlated with the
      presence or absence of a FLT3/ITD mutation. AG1295 was specifically cytotoxic to
      AML blasts harboring FLT3/ITD mutations. The results suggest that these mutations
      contribute to the leukemic process and that the FLT3 receptor represents a
      therapeutic target in AML. (Blood. 2001;98:885-887)

PMID- 11468195
TI  - Cerivastatin, a hydroxymethylglutaryl coenzyme a reductase inhibitor, improves
      endothelial function in elderly diabetic patients within 3 days.
AB  - BACKGROUND: The short-term effects of hydroxymethylglutaryl coenzyme A reductase
      inhibitors (statins) on endothelial function at doses that do not affect plasma
      lipid levels are not known. METHODS AND RESULTS: We investigated the short-term
      effects of cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor,
      on endothelial function and endothelium-related products in elderly diabetic
      patients. Twenty-seven elderly diabetic patients (aged 69.3+/-3.4 years), with or
      without mild hypercholesterolemia, were enrolled in this study, which tested
      cerivastatin treatment (0.15 mg/d) for 3 days. Endothelium-dependent flow
      mediated dilatation, endothelium-independent dilatation by nitroglycerin in the
      brachial artery, nitric oxide-related products (nitrite/nitrate and cGMP),
      endothelium-related products (von Willebrand Factor, soluble vascular cell
      adhesion molecule-1, and soluble intercellular adhesion molecule-1), and a marker
      of oxidant stress (8-isoprostane) were assessed. Levels of plasma lipids were not
      changed before and after treatment with cerivastatin. Flow-mediated dilatation
      was significantly increased by cerivastatin treatment, as were plasma
      nitrite/nitrate levels (from 16.9+/-3.4 to 22.0+/-3.7 micromol/L, P<0.05) and
      cGMP values. The percent of nitroglycerin-induced dilatation was not changed.
      Plasma concentrations of 8-isoprostane decreased, and levels of soluble vascular
      cell adhesion molecule also tended to decrease with cerivastatin. CONCLUSIONS:
      Improvement of endothelial function was in line with antiatherosclerotic effects.
      Cerivastatin improved impaired endothelial function in the short-term without
      affecting lipid profiles in elderly diabetic patients. This effect may be partly
      due to upregulation of endothelial nitric oxide synthase.

PMID- 11468196
TI  - Novel drug-delivery stent: intravascular ultrasound observations from the first
      human experience with the QP2-eluting polymer stent system.
AB  - BACKGROUND: The aim of this study was to use serial intravascular ultrasound
      (IVUS) to evaluate the long-term effect of stent-based 7-hexanoyltaxol (QP2, a
      taxane analogue) delivery on neointimal tissue growth within the stent and on
      vessel dimensions at the adjacent reference segments. METHODS AND RESULTS: Serial
      IVUS analyses (immediately after intervention and at follow-up at 8.3 months)
      were performed in 15 native coronary lesions treated with the QuaDS-QP2 stent.
      IVUS measurements were performed at 8 cross-sections in each target segment (4
      cross-sections within the stent and 2 cross-sections in each reference segment).
      At baseline, no significant plaque protrusion or thrombus was detected in the
      target segment. Mild incomplete stent apposition and edge dissection were
      observed in one and two cases, respectively. Percent expansion of the stent
      (minimum stent area/average reference lumen area) was 96.0+/-21.7%. At follow-up,
      mean neointimal area within the stent was 1.2+/-1.3 mm(2), and mean cross
      sectional narrowing (neointimal area/stent area) was 13.6+/-14.9%. At the vessel
      segments immediately adjacent to the stent, a significant increase in plaque area
      (1.9+/-2.6 mm(2), P=0.001) was observed, but vessel area remained unchanged.
      However, no patients showed clinically significant in-stent or edge restenosis
      (diameter stenosis >/=50%) during the follow-up period. CONCLUSIONS: The first
      human experience with the new drug-delivery stent showed a minimal amount of
      neointimal proliferation in the stented segment. Late lumen loss at the reference
      sites adjacent to the stent was acceptable and predominantly due to plaque
      proliferation.

PMID- 11468197
TI  - Independent association between plasma leptin levels and heart rate in heart
      transplant recipients.
AB  - BACKGROUND: Leptin, the protein product of the ob gene, has been linked to a
      faster heart rate in animal and human studies. The interaction between leptin and
      heart rate in the denervated heart is not known. Therefore, we studied the
      relationship between plasma leptin levels and heart rate in heart transplant
      recipients. METHODS AND RESULTS: We studied 32 male patients (mean age, 56.5+/
      9.3 years; range, 41 to 74 years) after orthotopic heart transplantation. All
      subjects underwent a physical examination, anthropometric measurements, blood
      chemistry analysis, and office blood pressure measurements. A blood sample was
      collected from each subject while fasting. In univariate analysis, heart rate was
      related to leptin levels (r=0.47, P=0.007) but heart rate was not related to
      systolic or diastolic blood pressure, mean arterial pressure, body mass index, or
      catecholamines. Leptin levels were only strongly associated with heart rate and
      body mass index (r=0.73, P<0.0001). In multivariate analysis, heart rate was
      independently and positively associated with leptin levels (F=2.61, P=0.017). We
      also observed a strong, independent association between leptin levels and body
      mass index (F=5.8, P<0.00001). CONCLUSIONS: We show an independent association
      between leptin levels and heart rate in heart transplant recipients. We speculate
      that this may be due, in part, to a direct effect of leptin on heart rate,
      conceivably mediated through cardiac leptin receptors.

PMID- 11468198
TI  - Use of intravascular ultrasound to compare effects of different strategies of
      lipid-lowering therapy on plaque volume and composition in patients with coronary
      artery disease.
AB  - BACKGROUND: We studied whether lipid-lowering therapy with atorvastatin (target
      LDL cholesterol [LDL-C] <100 mg/dL) compared with a moderate treatment regimen
      that used other lipid-lowering drugs led to a lesser progression of
      atherosclerosis and to different changes in plaque echogenicity in patients with
      coronary artery disease. METHODS AND RESULTS: This study was a 12-month, open
      label, randomized, multicenter trial, which used serial 3D intracoronary
      ultrasound to calculate plaque volume and plaque echogenicity. After
      transcatheter therapy, 131 patients were randomized (atorvastatin n=65, usual
      care n=66). The target plaque had to be a minor lesion (ie, a diameter stenosis
      of <50% on angiography). After 12 months, mean LDL-C was reduced from 155 to 86
      mg/dL in the atorvastatin group and from 166 to 140 mg/dL in the usual care
      group. Mean absolute plaque volume showed a larger increase in the usual care
      group compared with the atorvastatin group (usual care 9.6+/-28.1 mm(3),
      atorvastatin 1.2+/-30.4 mm(3); P=0.191). The hyperechogenicity index of the
      plaque increased to a larger extent for the atorvastatin group than for the usual
      care group, with a significant treatment effect for the percent change
      (atorvastatin 42.2%, usual care 10.1%; P=0.021). CONCLUSIONS: One year of lipid
      lowering therapy to <100 mg/dL LDL-C most likely led to a slowdown of plaque
      growth of minor lesions. The significantly larger increase in plaque
      hyperechogenicity is most likely due to a change in plaque composition.

PMID- 11468199
TI  - Maternal and paternal history of myocardial infarction and risk of cardiovascular
      disease in men and women.
AB  - BACKGROUND: Few studies have examined the effects of paternal and maternal
      history of myocardial infarction (MI), including age at MI, on cardiovascular
      disease (CVD) risk, particularly among women. METHODS AND RESULTS: We
      prospectively studied 22 071 men from the Physicians' Health Study and 39 876
      women from the Women's Health Study with data on parental history and age at MI.
      Among men, 2654 CVD cases developed over 13.0 years; among women, 563 CVD cases
      occurred over 6.2 years. Compared with men with no parental history, only
      maternal, only paternal, and both maternal and paternal history of MI conferred
      relative risks (RRs) of CVD of 1.71, 1.40, and 1.85; among women, the respective
      RRs were 1.46, 1.15, and 2.05. For men, maternal age at MI of <50, 50 to 59, 60
      to 69, 70 to 79, and >/=80 years had RRs of 1.00, 1.88, 1.88, 1.67, and 1.17; for
      women, the RRs for maternal age at MI of <50, 50 to 59, and >/=60 years were
      2.57, 1.33, and 1.52. Paternal age at MI of <50, 50 to 59, 60 to 69, 70 to 79,
      and >/=80 years in men had RRs of 2.19, 1.64, 1.42, 1.16, and 0.92; in women, for
      paternal age at MI of <50, 50 to 59, and >/=60 years, the RRs were 1.63, 1.33,
      and 1.13. CONCLUSIONS: An early history of parental MI (<60 years) conferred a
      greater risk of CVD than did MI at older ages. However, an increased risk of CVD
      remained for maternal age at MI of 70 to 79 years in men and >/=60 years in
      women, which suggests that any maternal history of MI may be important.

PMID- 11468200
TI  - Pharmacodynamics and pharmacokinetics of eptifibatide in patients with acute
      coronary syndromes: prospective analysis from PURSUIT.
AB  - BACKGROUND: Platelet deposition and aggregation are central to the pathogenesis
      of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic
      effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been
      delineated in healthy subjects but not in patients with ACS. We assessed effects
      of eptifibatide on ex vivo platelet aggregation in patients enrolled in the
      Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using
      Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS. METHODS AND RESULTS:
      Patients were randomly assigned to an intravenous bolus (180 microgram/kg) and 72
      hour infusion of eptifibatide (2.0 microgram/kg per minute, n=48) or placebo
      (n=50). We assessed correlations of plasma eptifibatide levels with receptor
      occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4,
      24, 48, and 72 hours during treatment and 4 and 8 hours after termination of
      infusion. Blood was collected in buffered citrate and D-phenylalanyl-L-prolyl-L
      arginine chloromethylketone anticoagulants. Although eptifibatide produced
      profound, prolonged inhibition of platelet aggregation during therapy,
      aggregation appeared to recover partially by 4 hours after the bolus. The
      aggregation response was greater with thrombin receptor agonist peptide versus
      ADP stimulation; inhibition of platelet aggregation was greater in blood samples
      anticoagulated with citrate versus D-phenylalanyl-L-prolyl-L-arginine
      chloromethylketone (PPACK). Plasma eptifibatide levels correlated significantly
      with receptor occupancy but not with inhibition of platelet aggregation.
      CONCLUSIONS: A bolus and infusion of eptifibatide inhibits platelet aggregation
      profoundly in patients with ACS and is followed by brief, partial recovery. These
      results enhance our understanding of the relation between pharmacodynamic and
      clinical effects of eptifibatide in such patients and may have important
      implications for its use in percutaneous interventions.

PMID- 11468201
TI  - Pharmacodynamics and pharmacokinetics of higher-dose, double-bolus eptifibatide
      in percutaneous coronary intervention.
AB  - BACKGROUND: Pharmacodynamics of eptifibatide, a cyclic heptapeptide antagonist of
      platelet glycoprotein IIb/IIIa, are substantially altered by anticoagulants that
      chelate calcium, resulting in overestimation ex vivo of the in vivo effects of
      this agent. We conducted a dose-ranging study to characterize the
      pharmacodynamics and pharmacokinetics of eptifibatide under physiological
      conditions. METHODS AND RESULTS: Patients (n=39) undergoing elective percutaneous
      coronary intervention were randomly assigned to an eptifibatide bolus followed by
      an infusion (180-microgram/kg bolus followed by 2 microgram/kg per minute or 250
      microgram/kg bolus followed by 3 microgram/kg per minute) for 18 to 24 hours. In
      a 2:1 ratio, these patients received either a second bolus of eptifibatide (90
      microgram/kg or 125 microgram/kg for the initial 180-microgram/kg or 250
      microgram/kg groups, respectively) or placebo 30 minutes after the initial bolus.
      Bleeding times, ex vivo platelet aggregation, receptor occupancy, and plasma
      eptifibatide levels at baseline and at 1, 2, 3, 4, 6, and 8 hours were evaluated.
      Platelet inhibition was dose dependent and >80% in all groups by steady state.
      The single-bolus regimens had a transient loss of inhibition at 1 hour,
      consistent with rapid distribution and drug elimination. Pharmacokinetic modeling
      suggested that optimal dosing of eptifibatide would be obtained with a 180
      microgram/kg bolus and a 2-microgram/kg per minute infusion followed by a second
      180-microgram/kg bolus 10 minutes later. CONCLUSIONS: A novel higher-dose, double
      bolus regimen of eptifibatide in coronary intervention attains and maintains >90%
      inhibition of platelet aggregation in >90% of patients, providing the
      pharmacodynamic construct for the design of the Enhanced Suppression of the
      Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of adjunctive
      eptifibatide in coronary stent implantation.

PMID- 11468202
TI  - Long-term prognostic value of coronary calcification detected by electron-beam
      computed tomography in patients undergoing coronary angiography.
AB  - BACKGROUND: Electron-beam CT (EBCT) quantification of coronary artery
      calcification (CAC) allows noninvasive assessment of coronary atherosclerosis. We
      undertook a follow-up study to determine whether CAC extent, measured at the time
      of angiography by EBCT, predicted future hard cardiac events, comprising cardiac
      death and nonfatal myocardial infarction (MI). We also assessed the potential of
      selected coronary artery disease (CAD) risk factors, prior CAD event history (MI
      or revascularization), and angiographic findings (number of diseased vessels and
      overall disease burden) to predict subsequent hard events. METHODS AND RESULTS:
      Two hundred eighty-eight patients who underwent contemporaneous coronary
      angiography and EBCT scanning were contacted after a mean of 6.9 years. Vital
      status and history of MI during follow-up were determined. Cox proportional
      hazards models were used to compare the predictive ability of CAC extent with
      selected CAD risk factors, CAD event history, and angiographic findings. Median
      CAC score was 160 (range 0 to 7633). The 22 patients who experienced hard events
      during follow-up were older and had more extensive CAC and angiographic disease
      (P<0.05). Only 1 of 87 patients with CAC score <20 experienced a subsequent hard
      event during follow-up. Event-free survival was significantly higher for patients
      with CAC scores <100 than for those with scores >/=100 (relative risk 3.20; 95%
      CI 1.17 to 8.71). When a stepwise multivariable model was used, only age and CAC
      extent predicted hard events (risk ratios 1.72 and 1.88, respectively; P<0.05).
      CONCLUSIONS: In patients undergoing angiography, CAC extent on EBCT is highly
      predictive of future hard cardiac events and adds valuable prognostic
      information.

PMID- 11468203
TI  - Respiratory modulation of muscle sympathetic nerve activity in patients with
      chronic heart failure.
AB  - BACKGROUND: Sympathoexcitation and respiratory instability are closely related to
      worsening of chronic heart failure. To elucidate the dynamic nature of
      respiratory modulation of sympathetic activity in patients with heart failure, we
      studied within-breath variation of muscle sympathetic nerve activity (MSNA) under
      various ventilatory volumes. METHODS AND RESULTS: MSNA, blood pressure, and
      respiratory flow were recorded in 23 patients with left ventricular ejection
      fraction </=45%. Within-breath suppression of MSNA (neural silence) was found in
      11 patients (MSNA bursts: 71+/-10/100 heartbeats) but not in the remaining 12
      patients (MSNA bursts: 88+/-8/100 heartbeats). Patients without neural silence
      had a smaller tidal volume (391+/-70 versus 267+/-75 mL/m(2), P<0.01) and a
      higher respiratory rate (15+/-2 versus 19+/-4 breaths/min, P<0.01) during
      spontaneous respiration than those with neural silence. The relationship between
      tidal volume and minimal amplitude of MSNA bursts in each breath was obtained
      during random-interval breathing and fitted by an exponential function. The curve
      of patients without neural silence was shifted to the right and upward, which
      suggests that a greater tidal volume was required to suppress MSNA (227+/-70
      versus 437+/-195 mL/m(2), P<0.01). CONCLUSIONS: Sympathoexcitation in patients
      with chronic heart failure is closely related to both a decrease in resting tidal
      volume and an attenuated sympathoinhibitory effect of lung inflation reflex.

PMID- 11468204
TI  - Sildenafil inhibits hypoxia-induced pulmonary hypertension.
AB  - BACKGROUND: This study investigated the effect of the phosphodiesterase 5
      inhibitor sildenafil on the pulmonary vascular response to hypoxia in humans and
      mice. METHODS AND RESULTS: In a randomized, double-blind study, sildenafil 100 mg
      or placebo was given orally to 10 healthy volunteers 1 hour before breathing 11%
      O(2) for 30 minutes. Pulmonary artery pressure (PAP) was measured with an
      indwelling right heart catheter. The acute 56% increase in mean PAP produced by
      hypoxia during placebo treatment (mean PAP [mean+/-SD mm Hg]: normoxia 16.0+/-2.1
      versus hypoxia 25.0+/-4.8) was almost abolished by sildenafil (normoxia 16.0+/
      2.1 versus hypoxia 18.0+/-3.6), with no significant effect on systemic blood
      pressure. In the isolated perfused lung of wild-type and endothelial nitric oxide
      synthase (eNOS)-deficient mice, sildenafil markedly blunted acute hypoxic
      pulmonary vasoconstriction. Wild-type mice dosed orally with the drug (25 mg. kg(
      1). d(-1)) throughout 3 weeks of exposure to hypoxia (10% O(2)) exhibited a
      significant reduction in right ventricular systolic pressure (placebo versus
      sildenafil: 43.3+/-9.9 versus 29.9+/-9.7 mm Hg, P<0.05) coupled with a small
      reduction in right ventricular hypertrophy and inhibition of pulmonary vascular
      remodeling. In eNOS mutant mice, sildenafil attenuated the increase in right
      ventricular systolic pressure but without a significant effect on right
      ventricular hypertrophy or vascular remodeling. CONCLUSIONS: Sildenafil
      attenuates hypoxia-induced pulmonary hypertension in humans and mice and offers a
      novel approach to the treatment of this condition. The eNOS-NO-cGMP pathway
      contributes to the response to sildenafil, but other biochemical sources of cGMP
      also play a role. Sildenafil has beneficial pulmonary hemodynamic effects even
      when eNOS activity is impaired.

PMID- 11468205
TI  - Exercise pathophysiology in patients with primary pulmonary hypertension.
AB  - BACKGROUND: Patients with primary pulmonary hypertension (PPH) have a pulmonary
      vasculopathy that leads to exercise intolerance due to dyspnea and fatigue. To
      better understand the basis of the exercise limitation in patients with PPH,
      cardiopulmonary exercise testing (CPET) with gas exchange measurements, New York
      Heart Association (NYHA) symptom class, and resting pulmonary hemodynamics were
      studied. METHODS AND RESULTS: We retrospectively evaluated 53 PPH patients who
      had right heart catheterization and cycle ergometer CPET studies to maximum
      tolerance as part of their clinical workups. No adverse events occurred during
      CPET. Reductions in peak O(2) uptake (VO(2)), anaerobic threshold, peak O(2)
      pulse, rate of increase in VO(2), and ventilatory efficiency were consistently
      found. NYHA class correlated well with the above parameters of aerobic function
      and ventilatory efficiency but less well with resting pulmonary hemodynamics.
      CONCLUSIONS: Patients with PPH can safely undergo noninvasive cycle ergometer
      CPET to their maximal tolerance. The CPET abnormalities were consistent and
      characteristic and correlated well with NYHA class.

PMID- 11468206
TI  - Prediction of long-term outcomes by signal-averaged electrocardiography in
      patients with unsustained ventricular tachycardia, coronary artery disease, and
      left ventricular dysfunction.
AB  - BACKGROUND: An abnormal signal-averaged ECG (SAECG) is a noninvasive marker of
      the substrate of sustained ventricular tachycardia after myocardial infarction.
      We assessed its prognostic ability in patients with asymptomatic unsustained
      ventricular tachycardia, coronary artery disease, and left ventricular
      dysfunction. METHODS AND RESULTS: A blinded core laboratory analyzed SAECG
      tracings from 1925 patients in a multicenter trial. Cox proportional hazards
      modeling was used to examine individual and joint relations between SAECG
      variables and arrhythmic death or cardiac arrest (primary end point), cardiac
      death, and total mortality. We also assessed the prognostic utility of SAECG at
      different levels of ejection fraction (EF). A filtered QRS duration >114 ms
      (abnormal SAECG) independently predicted the primary end point and cardiac death,
      independent of clinical variables, cardioverter-defibrillator implantation, and
      antiarrhythmic drug therapy. With an abnormal SAECG, the 5-year rates of the
      primary end point (28% versus 17%, P=0.0001), cardiac death (37% versus 25%,
      P=0.0001), and total mortality (43% versus 35%, P=0.0001) were significantly
      higher. The combination of EF <30% and abnormal SAECG identified a particularly
      high-risk subset that constituted 21% of the total population. Thirty-six percent
      and 44% of patients with this combination succumbed to arrhythmic and cardiac
      death, respectively. CONCLUSIONS: SAECG is a powerful predictor of poor outcomes
      in this population. The noninvasive combination of an abnormal SAECG and reduced
      EF may have utility in selecting high-risk patients for intervention.

PMID- 11468207
TI  - Investigation of coronary venous anatomy by retrograde venography in patients
      with malignant ventricular tachycardia.
AB  - BACKGROUND: The coronary venous system is increasingly used for left ventricular
      or biventricular pacing in patients with severe heart failure. The present study
      investigated the structure of the coronary veins in patients presenting with
      structural heart disease and malignant ventricular tachyarrhythmias. The
      availability of veins for possible lead placement was assessed. METHODS AND
      RESULTS: The number, relative size, and location of coronary veins were evaluated
      by retrograde venography in 129 patients undergoing cardioverter-defibrillator
      implantation. Detailed x-ray image analysis was performed in 86 patients, for
      whom optimal coronary sinus occlusion and vein visualization was achieved. The
      anterior interventricular vein and the middle cardiac vein were visible in 85
      (99%) of 86 patients and in 86 (100%) of 86 patients, respectively. Between these
      2 veins, at least 1 additional prominent vein was visible in 85 (99%) of 86
      patients. Just 1 vein was present in 44 (51%) of 86 patients. Two veins were
      observed in 40 (46%) of 86 patients, and >2 veins were visualized in 2 (2%) of 86
      patients. Venous anatomy allowed positioning of a 0.014-in guidewire in a
      coronary vein in 115 (93%) of 124 patients. CONCLUSIONS: The presence, diameter,
      angulation, and tortuosity of veins as visualized by retrograde venography
      determine their acceptability for the placement of a lead in a predetermined
      location. Despite the considerable variability of the coronary venous system
      among patients, a lateral vessel for lead introduction was available in 82%, and
      a posterior or lateral vessel was available in 99% of individuals within a
      patient population that could potentially benefit from a lead on the left
      ventricle.

PMID- 11468208
TI  - Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart
      disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout
      mice.
AB  - BACKGROUND: To test whether deficiency in endothelial nitric oxide synthase
      (eNOS) affects atherosclerosis development, we compared lesion formation in
      apolipoprotein E (apoE)/eNOS-double knockout (DKO) and apoE-knockout (KO) control
      animals. METHODS AND RESULTS: After 16 weeks of "Western-type" diet, apoE/eNOS
      DKO males and females showed significant increases in lesion area of 93.6% and
      59.2% compared with apoE-KO mice. All apoE/eNOS-DKO animals studied developed
      peripheral coronary arteriosclerosis, associated with perivascular and myocardial
      fibrosis, whereas none of the apoE-KO mice did. Transthoracic echocardiography
      showed a significantly increased left ventricular wall thickness and decreased
      fractional shortening in DKO animals. Mean arterial pressure was increased in DKO
      mice and was comparable in degree to eNOS-KO animals. Male DKO animals developed
      atherosclerotic abdominal aneurysms and aortic dissection. CONCLUSIONS: eNOS
      deficiency increases atherosclerosis in Western-type diet-fed apoE-KO animals and
      introduces coronary disease and an array of cardiovascular complications,
      including spontaneous aortic aneurysm and dissection. This phenotype constitutes
      the first murine model to demonstrate distal coronary arteriosclerosis associated
      with evidence of myocardial ischemia, infarction, and heart failure. Hypertrophy
      and reduced left ventricular function cannot be explained by increased blood
      pressure alone, because eNOS-KO animals do not develop these complications.

PMID- 11468209
TI  - Pioglitazone enhances cytokine-induced apoptosis in vascular smooth muscle cells
      and reduces intimal hyperplasia.
AB  - BACKGROUND: Cytokines induce apoptosis in vascular disease lesions through
      enhancement of inducible nitric oxide (NO) synthase (iNOS) activation. The
      thiazolidinediones, novel insulin-sensitizing agents, have been demonstrated to
      modulate cytokine-induced NO production. We have investigated the role of
      pioglitazone in the apoptosis of vascular smooth muscle cells (VSMCs) in vitro
      and developed intimal hyperplasia in vivo. METHODS AND RESULTS: Pioglitazone (0.1
      to 10 micromol/L) significantly enhanced cytokine-induced expression of iNOS and
      NO production in a dose-dependent manner in rat VSMCs, but 15-deoxy-Delta(12,14)
      prostaglandin J2 (up to 10 micromol/L), a native peroxisome proliferator
      activated receptor-gamma ligand, showed no effect. Pioglitazone also
      significantly enhanced reduction of cell viability, as evidenced by the increase
      in the number of TUNEL-positive cells. All of these effects of pioglitazone were
      blocked by treatment with N-monomethyl-L-arginine, an NO synthesis inhibitor. In
      an in vivo study with a balloon-injured rat carotid artery, neointimal thickness
      had reached maximum levels at 2 weeks after injury. Then, rats were fed with or
      without pioglitazone (3 mg. kg(-1). d(-1)) for an additional week. The ratio of
      intima to media area of carotid artery was significantly decreased by 30%, and
      the ratio of apoptotic cells in neointima was significantly increased in
      pioglitazone-treated rats compared with vehicle-treated control rats.
      CONCLUSIONS: Pioglitazone enhanced apoptosis in an NO-dependent manner in
      cytokine-activated VSMCs and induced significant regression of intimal
      hyperplasia in balloon-injured rat carotid artery. It appears that pioglitazone
      is a potent apoptosis inducer in vascular lesions, providing a novel
      pharmacological strategy to prevent restenosis after vascular intervention.

PMID- 11468210
TI  - Destruction of contrast microbubbles by ultrasound: effects on myocardial
      function, coronary perfusion pressure, and microvascular integrity.
AB  - BACKGROUND: Recent experimental data indicate that ultrasound-induced destruction
      of ultrasound contrast microbubbles can cause immediate rupture of the
      microvessels in which these microbubbles are located. METHODS AND RESULTS: To
      examine the functional and morphological significance of these findings in the
      heart, isolated rabbit hearts were perfused retrogradely with buffer containing
      ultrasound contrast agents and were insolated at increasing levels of acoustic
      energy with a broadband transducer emitting at 1.8 MHz and receiving at 3.6 MHz
      and operated in the triggered mode (1 Hz). At the end of each experiment, the
      hearts were fixed in glutaraldehyde and examined with light microscopy. Neither
      exposure to ultrasound alone or to contrast alone affected left ventricular
      developed pressure. By contrast, simultaneous exposure to contrast and ultrasound
      resulted in a reversible, transient mechanical index (MI)-dependent decrease in
      left ventricular developed pressure (to 83+/-5% of baseline at an MI of 1.6) and
      a transient MI-dependent increase in coronary perfusion pressure (to 120+/-6% of
      baseline at an MI of 1.6). Myocardial lactate release also showed significant
      increases with increasing MIs. Macroscopically, areas of intramural hemorrhage
      were identified over the beam elevation in hearts exposed to both contrast and
      high-MI ultrasound. Light microscopy revealed the presence of capillary ruptures,
      erythrocyte extravasation, and endothelial cell damage. The mean percentage of
      capillaries ruptured at an MI of 1.6 was 3.6+/-1.4%. CONCLUSIONS: Simultaneous
      exposure of isolated rabbit hearts to ultrasound and contrast agents results in
      an MI-dependent, transient depression of left ventricular contractile function, a
      rise in coronary perfusion pressure, an increase in lactate production, and
      limited capillary ruptures.

PMID- 11468211
TI  - Eplerenone suppresses constrictive remodeling and collagen accumulation after
      angioplasty in porcine coronary arteries.
AB  - BACKGROUND: Coronary artery angioplasty triggers healing that causes constrictive
      remodeling. Because collagen accumulation correlates with constrictive remodeling
      and aldosterone has been implicated in collagen accumulation, we examined how
      aldosterone and the mineralocorticoid receptor antagonists spironolactone and
      eplerenone affect remodeling and collagen in porcine coronary and iliac arteries
      after angioplasty. METHODS AND RESULTS: Twenty-four pigs were allocated into 4
      treatment groups: oral eplerenone (100 mg/d), oral spironolactone (200 mg/d),
      subcutaneous aldosterone (400 microgram/d), or no treatment. Twenty-eight days
      after angioplasty of the coronary arteries, eplerenone increased total vessel
      area by 30% (P<0.05) and luminal area by nearly 60% (P<0.05) compared with the no
      treatment group, without affecting neointima size. These effects were accompanied
      by a 65% reduction in neointimal and medial collagen density (both P<0.05).
      Spironolactone was less effective, and aldosterone tended to exert opposite
      effects on coronary artery structure after angioplasty. These effects were not
      observed in angioplastied iliac arteries. CONCLUSIONS: Eplerenone attenuates
      constrictive remodeling after coronary artery angioplasty by mechanisms involving
      reduction in collagen accumulation, which thus appears to be an important
      contributor to constrictive remodeling of angioplastied coronary arteries.

PMID- 11468212
TI  - Pathological analysis of local delivery of paclitaxel via a polymer-coated stent.
AB  - BACKGROUND: Paclitaxel can inhibit vascular smooth muscle proliferation in vitro,
      and early studies suggest that paclitaxel may be useful in preventing restenosis.
      Early and late intimal growth and local vascular pathological changes associated
      with paclitaxel delivered via stents have not been fully explored. METHODS AND
      RESULTS: Localized drug delivery was accomplished with balloon-expandable
      stainless steel stents coated with a cross-linked biodegradable polymer,
      chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel.
      CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of
      paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents
      (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand
      White rabbits, which were killed 28 days after implant. Mean neointimal thickness
      at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents
      containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus
      CSG-coated stents without paclitaxel. However, histological findings suggested
      incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel
      containing stents consisting of persistent intimal fibrin deposition,
      intraintimal hemorrhage, and increased intimal and adventitial inflammation.
      Stents coated with CSG alone (without paclitaxel) had similar neointimal growth
      as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal
      growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0
      microgram of paclitaxel CONCLUSIONS: CSG coating appears to be a promising medium
      for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima
      formation but are associated with evidence of incomplete healing at 28 days.
      However, neointimal suppression was not maintained at 90 days.

PMID- 11468213
TI  - Prophylaxis of restenosis with (186)re-labeled stents in a rabbit model.
AB  - BACKGROUND: Intraluminal beta-irradiation has been shown to decrease neointimal
      proliferation after angioplasty in experimental models. The purpose of this study
      was to test the technical feasibility and biological effects of (186)Re-labeled
      stents. METHODS AND RESULTS: Thirty-four New Zealand White rabbits were fed a
      0.5% cholesterol diet before balloon angioplasty and insertion of Palmaz stents
      in the infrarenal aorta. The animals were killed 7 weeks after stent
      implantation. Two of 34 animals died prematurely (aortic leak, pneumonia).
      Control stents (n=7) were compared with (186)Re stents (2.6 MBq [n=6], 8.1 MBq
      [n=5], 16.0 MBq [n=6], and 25.3 MBq [n=8]). Stent application was successful in
      all cases. No thrombus occlusion was observed. After 7 weeks, neointima formation
      was 2.2+/-0.2 mm(2) in the control group. In the treatment groups, a dose
      dependent neointima reduction was detectable (0.5+/-0.5 mm(2) [2.6 MBq], 0.4+/
      0.4 mm(2) [8.1 MBq], and 0 mm(2) [16.0 MBq, 25.3 MBq]). No induction of
      neointimal formation was observed at the edges of the stents. Radiation resulted
      in delayed reendothelialization. CONCLUSIONS: (186)Re stents were capable of
      reducing neointima formation in a dose-dependent fashion. (186)Re stents did not
      cause late thrombosis or neointimal induction at the stent margins in the
      observation period of 7 weeks.

PMID- 11468214
TI  - Mechanoelectrical feedback: role of beta-adrenergic receptor activation in
      mediating load-dependent shortening of ventricular action potential and
      refractoriness.
AB  - BACKGROUND: Augmented preload increases myocardial excitability by shortening
      action potential duration (APD). The mechanism governing this phenomenon is
      unknown. Because myocardial stretch increases intracellular cAMP, we hypothesized
      that load-dependent changes in myocardial excitability are mediated by beta
      adrenergic stimulation of a cAMP-sensitive K(+) current. METHODS AND RESULTS: The
      effects of propranolol on load-induced changes in electrical excitability were
      studied in 7 isolated ejecting canine hearts. LV monophasic APD at 50% and 90%
      repolarization (MAPD(50) and MAPD(90)) and refractoriness were determined at low
      (9+/-3 mL) and high (39+/-4 mL) load before and after beta-adrenergic blockade.
      During control, the MAPD(50) decreased from 193+/-26 to 184+/-26 ms with
      increased load, as did the MAPD(90) (238+/-28 to 233+/-28 ms), P</=0.04. Similar
      changes were observed in ventricular refractoriness. Treatment with propranolol
      completely abolished these load-induced effects. Myocardial catecholamine
      depletion with reserpine in 2 hearts also abolished changes in MAPD and
      excitability in response to increased preload. CONCLUSIONS: Increases in
      ventricular load mediate a decrease in ventricular APD and refractoriness through
      activation of the beta-adrenergic receptor. An increase in a cAMP-mediated K(+)
      current, possibly the slowly activating delayed rectifier I(Ks), may account in
      part for this form of mechanoelectrical coupling.

PMID- 11468215
TI  - Cardiovascular risk assessment based on US cohort studies: findings from a
      National Heart, Lung, and Blood institute workshop.

PMID- 11468216
TI  - Multirow detector computed tomography assessment of intraseptal dissection and
      ventricular pseudoaneurysm in postinfarction ventricular septal defect.

PMID- 11468217
TI  - Hormone replacement therapy and cardiovascular disease: a statement for
      healthcare professionals from the American Heart Association.

PMID- 11468218
TI  - Absent right pulmonary artery with coronary collaterals supplying the affected
      lung.

PMID- 11468219
TI  - Microarrays: the reincarnation of multiplexing in laboratory medicine, but now
      more relevant?

PMID- 11468220
TI  - Biochemical markers of bone turnover: why theory, research, and clinical practice
      are still in conflict.

PMID- 11468221
TI  - Analysis issues for gene expression array data.

PMID- 11468222
TI  - Direct and indirect free thyroxine assay methods: theory and practice.
AB  - BACKGROUND: For the diagnosis of thyroid disease, measurement of "free hormone"
      is generally accepted as an appropriate measure. However, valid assays measuring
      the free fraction of thyroxine (FT4) ideally must perform without bias, despite
      large variations in the concentrations and affinities of serum T4-binding
      proteins in the population. Several approaches have been taken to overcome such
      bias, and these have created considerable controversy in the field over the past
      decade. APPROACH: This review, from both a historical and an analytical
      standpoint, charts the progress made over more than 30 years in improvements to
      the performance of assays in common use for the measurement of FT4 in serum or
      plasma. It reexamines the theory behind early approaches to such assays [for
      example, the free thyroxine index (FTI) method], that preceded more accurate, two
      step immunoassays or one-step analog techniques. It evaluates the continuous
      refinements to the latter assays that by now have largely supplanted the FTI
      approach and where the deficiencies that so exercised clinical chemists in the
      past have been virtually eliminated in the leading assays. CONTENT: The basic
      Mass Action theory underpinning all such methods is discussed by assessing how
      far each particular approach obeys the criteria the theory imposes. In this, it
      is not the intention of the review to dissect individual commercial or academic
      assays, but rather to give guidance where appropriate as to how any assay said to
      measure FT4 can be conveniently evaluated by those intending to use it. Examples
      are given where inappropriate tests may wrongly imply assay invalidity by
      misinterpreting how FT4 assays work. SUMMARY: Detailed knowledge of the
      underlying theory is essential when devising tests for direct FT4 assays, to
      ensure that such tests do not overstep the practical limits of assay validity.

PMID- 11468223
TI  - Neonatal screening for galactosemia by quantitative analysis of hexose
      monophosphates using tandem mass spectrometry: a retrospective study.
AB  - BACKGROUND: Classic galactosemia (OMIM 230400) is an inherited disorder in the
      metabolism of galactose caused by deficiency of the enzyme galactose 1-phosphate
      uridyl transferase (EC 2.7.7.12). Galactosemia leads to accumulation of galactose
      and galactose 1-phosphate (gal-1-P) in blood and tissues and, if untreated,
      produces neonatal death or severe mental retardation, cirrhosis of the liver, and
      cataracts. Hence, the disorder is included in many neonatal screening programs.
      METHODS: We retrospectively analyzed filter-paper blood samples obtained 4-8 days
      postpartum for routine neonatal screening from 12 galactosemia patients and 2055
      random controls. Total hexose monophosphates (HMPs) were used as a marker of gal
      1-P and were assayed by negative-ion mode electrospray tandem mass spectrometry
      (tandem MS) with settings biased toward gal-1-P detection. The predominant
      precursor/product ion pair m/z 259/79 was used to quantify total HMPs by external
      standardization. RESULTS: Linear calibration curves were obtained in the range 0
      8 mmol/L gal-1-P. The detection limit was 0.1 mmol/L HMP, and total CVs ranged
      from 13% at the detection limit to <8% at >1 mmol/L HMP. The method was in
      agreement with an alkaline phosphatase-galactose dehydrogenase method. All
      samples from galactosemia patients contained increased HMP concentrations (range
      for patients, 2.6-5.2 mmol/L; range for reference group, <0.10-0.94 mmol/L). The
      diagnostic sensitivity and specificity were 100% at a cutoff of 1.2 mmol/L HMP. A
      Duarte/classic galactosemia compound heterozygous sample could be discriminated
      clearly from both patient and reference samples. CONCLUSION: Quantitative
      analysis of HMPs by tandem MS can be used in laboratory investigations of
      galactosemia.

PMID- 11468224
TI  - Genotyping single-nucleotide polymorphisms by the invader assay with dual-color
      fluorescence polarization detection.
AB  - BACKGROUND: The PCR-Invader assay is a robust, homogeneous assay that has been
      shown to be highly sensitive and specific in genotyping single-nucleotide
      polymorphism (SNP) markers. In this study, we introduce two changes to improve
      the assay: (a) we streamline the PCR-Invader method by assaying both alleles for
      each SNP in one reaction; and (b) we reduce the cost of the method by adopting
      fluorescence polarization (FP) as the detection method. METHODS: PCR product was
      incubated with Invader oligonucleotide and two primary probes at 93 degrees C for
      5 min. Signal probes corresponding to the cleaved flaps of the primary probes
      [labeled with fluorescein and 6-carboxytetramethylrhodamine (TAMRA) dye] and
      Cleavase VIII enzyme (a flap endonuclease) were then added to the mixture. This
      reaction mixture was incubated at 63 degrees C for 5 min. FP measurements were
      made with a fluorescence plate reader. RESULTS: Eighty-eight individuals were
      genotyped across a panel of 10 SNPs, using PCR product as template, for a total
      of 880 genotypes. An average "no call" rate of 3.2% was observed after first
      round of experiments. PCR products were remade in those samples that failed to
      produce any genotype in the first round, and all gave clear-cut genotypes. When
      the genotypes determined by the PCR-Invader assay and template-directed dye
      terminator incorporation assay with FP were compared, they were in 100%
      concordance for all SNP markers and experiments. CONCLUSIONS: The improvements
      introduced in this study make PCR-Invader assay simpler and more cost-effective,
      and therefore more suitable for high-throughput genotyping.

PMID- 11468225
TI  - Determination of acid alpha-glucosidase activity in blood spots as a diagnostic
      test for Pompe disease.
AB  - BACKGROUND: Pompe disease is an autosomal recessive disorder of glycogen
      metabolism that is characterized by a deficiency of the lysosomal acid alpha
      glucosidase. Enzyme replacement therapy for the infantile and juvenile forms of
      Pompe disease currently is undergoing clinical trials. Early diagnosis before the
      onset of irreversible pathology is thought to be critical for maximum efficacy of
      current and proposed therapies. In the absence of a family history, the
      presymptomatic detection of these disorders ideally can be achieved through a
      newborn-screening program. Currently, the clinical diagnosis of Pompe disease is
      confirmed by the virtual absence, in infantile onset, or a marked reduction, in
      juvenile and adult onset, of acid alpha-glucosidase activity in muscle biopsies
      and cultured fibroblasts. These assays are invasive and not suited to large-scale
      screening. METHODS: A sensitive immune-capture enzyme activity assay for the
      measurement of acid alpha-glucosidase protein was developed and used to determine
      the activity of this enzyme in dried-blood spots from newborn and adult controls,
      Pompe-affected individuals, and obligate heterozygotes. RESULTS: Pompe-affected
      individuals showed an almost total absence of acid alpha-glucosidase activity in
      blood spots. The assay showed a sensitivity and specificity of 100% for the
      identification of Pompe-affected individuals. CONCLUSIONS: The determination of
      acid alpha-glucosidase activity in dried-blood spots is a useful, noninvasive
      diagnostic assay for the identification of Pompe disease. With further
      validation, this procedure could be adapted for use with blood spots collected in
      newborn-screening programs.

PMID- 11468226
TI  - Solid-phase amplification for detection of C282y and H63D hemochromatosis (HFE)
      gene mutations.
AB  - BACKGROUND: There is a need for simple, rapid, and inexpensive methods for the
      detection of single-nucleotide polymorphisms. Our aim was to develop a single
      tube ELISA-like PCR assay and evaluate it by detecting the common C282Y and H63D
      mutations found in the hemochromatosis gene (HFE) by use of clinical samples.
      METHODS: The method, termed solid-phase amplification (SPA), involves dual liquid
      and solid-phase amplification of a target sequence by the use of two PCR
      primers, one of which is in two forms: the first is covalently immobilized to the
      wall of a microwell, and the second is free in solution. During allele-specific
      amplification, both the free and solid-phase amplicons are labeled by
      incorporation of digoxigenin (DIG)-dUTP. The amount of surface-bound amplicon is
      determined colorimetrically by the use of an alkaline phosphatase-anti-DIG-Fab
      conjugate and p-nitrophenyl phosphate. RESULTS: Two different amplicon-labeling
      methods were evaluated. Analysis of 173 clinical samples for the C282Y and H63D
      HFE point mutations with SPA revealed that only one sample was incorrectly
      diagnosed, apparently because of operator error, when compared with conventional
      restriction fragment length polymorphism assay results. CONCLUSIONS: The SPA
      assay has potential for medium-scale mutation detection, having the advantage of
      being manipulatively simple and immediately adaptable for use in clinical
      laboratories with existing ELISA instrumentation.

PMID- 11468227
TI  - Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding
      the cardiac HERG/MiRP1 ion channel: implications for acquired and congenital long
      Q-T syndrome.
AB  - BACKGROUND: The voltage-gated, rapid-delayed rectifier current (I(Kr)) is
      important for repolarization of the heart, and mutations in the genes coding for
      the K+-ion channel conducting this current, i.e., KCNH2 for the alpha-subunit
      HERG and KCNE2 for the beta-subunit MiRP1, cause acquired and congenital long Q-T
      syndrome (LQTS) and other cardiac arrhythmias. METHODS: We developed a robust
      single-strand conformation polymorphism-heteroduplex screening analysis, with
      identical thermocycling conditions for all PCR reactions, covering all of the
      coding exons in KCNH2 and KCNE2. The method was used to screen 40 unrelated LQTS
      patients. RESULTS: Eleven mutations, of which six were novel, were found in
      KCNH2. Interestingly, six mutations were found in the region of the gene coding
      for the Per-Arnt-Sim (PAS) and PAS-S1 regions of the HERG protein, stressing the
      need to examine the entire gene when screening for mutations. No mutations were
      found in KCNE2, suggesting that direct involvement of MiRP1 in LQTS is rare.
      Furthermore, four novel single-nucleotide polymorphisms (SNPs) and one amino acid
      polymorphism (R1047L) were identified in KCNH2, and one novel SNP and one
      previously known amino acid polymorphism (T8A) were found in KCNE2. CONCLUSIONS:
      The potential role of rare polymorphisms in the HERG/MiRP1 K+-channel should be
      clarified with respect to drug interactions and susceptibility to arrhythmia and
      sudden death.

PMID- 11468228
TI  - Vitamin B12 treatment normalizes metabolic markers but has limited clinical
      effect: a randomized placebo-controlled study.
AB  - BACKGROUND: The clinical significance of increased plasma methylmalonic acid (P
      MMA) is unclear. We assessed the efficacy of vitamin B12 treatment in reducing P
      MMA and plasma total homocysteine compared with the clinical benefits of
      treatment. METHODS: We studied 140 individuals with mildly to modestly increased
      P-MMA (0.40-2.00 micromol/L), not previously treated with vitamin B12, in a
      randomized, placebo-controlled study. A detailed medical history was obtained,
      and laboratory tests as well as an objective neurologic disability score were
      performed at baseline and 3 months after the start of intervention. RESULTS: P
      MMA (P <0.001) or plasma total homocysteine (P <0.001) decreased in the treatment
      group vs the placebo group, but no significant difference was found in the change
      of blood hemoglobin (P = 0.18) and mean cell volume (P = 0.71). Changes in
      symptom scores did not differ between the groups for symptoms of anemia (P =
      0.63), neurologic symptoms (P = 0.21), gastroenterologic symptoms (P = 0.32), or
      the Neurological Disability Score (P = 0.85). CONCLUSIONS: Treatment with vitamin
      B12 reduces P-MMA and plasma total homocysteine, but individuals with a mild to
      modest increase in P-MMA may have only limited clinical benefit from vitamin B12
      treatment, at least in the short term.

PMID- 11468229
TI  - Intermethod discordance for alpha-fetoprotein measurements in Fanconi anemia.
AB  - BACKGROUND: The significantly higher serum alpha-fetoprotein (AFP) in patients
      with Fanconi anemia (FA) than in non-FA aplastic patients has potential
      diagnostic utility, but the increase is method-dependent. The aim of this study
      was to compare five AFP assays on FA and non-FA samples and to investigate
      possible explanations for FA-specific discrepancies. METHODS: Two methods
      available in our laboratory (Kryptor and IMx) were compared on 59 FA and 27 non
      FA patient samples. Kryptor, Immulite, Elecsys, Immuno-I, and Elsa-2 methods were
      then compared on 14 FA and 14 non-FA patient samples. The AFP glycosylation
      profile was analyzed by electrophoretic separation in a lectin-containing gel.
      RESULTS: With all six methods, AFP values were significantly higher in FA than in
      non-FA patients, but the diagnostic precision and optimal cutoff values varied.
      Indeed, two methods reached 100% sensitivity and specificity, but in other
      methods, one or both of these parameters were significantly <100%. Neither
      heterophilic antibodies nor a specific glycosylation profile was detected in FA
      samples. CONCLUSIONS: AFP results are method-dependent in FA. New methods must be
      evaluated before use in differential diagnosis of aplastic patients.

PMID- 11468230
TI  - Clinical evaluation of the Elecsys beta-CrossLaps serum assay, a new assay for
      degradation products of type I collagen C-tlopeptides.
AB  - BACKGROUND: The Elecsys beta-CrossLaps serum assay measures type I collagen
      degradation fragments (beta-CTx) that contain the beta-isomerized octapeptide
      EKAHD-beta-GGR. We investigated the analytical performance of the assay and
      changes in beta-CrossLaps in patients with metabolic bone diseases. METHODS: The
      electrochemiluminescent sandwich immunoassay uses two monoclonal antibodies
      directed against different regions of the linear EKAHD-beta-GGR. RESULTS: beta
      CrossLaps (beta-CTx) immunoreactivity was stable in serum and plasma stored at 4
      degrees C for 24 h or at room temperature for 4 h, and it did not decrease
      appreciably in samples stored at -30 degrees C for 12 weeks. Nine cycles of
      repeated freezing-thawing did not affect serum beta-CTx. The intra- and
      interassay imprecision (CVs) for four samples was < or = 2.6% (n = 10) and < or =
      4.1% (n = 10), respectively. The mean day-to-day biological variation (CV) was
      20% in 10 postmenopausal women (n = 10 days). Serum beta-CTx and osteocalcin were
      correlated in patients with hyperparathyroidism (r = 0.796; P <0.0001; n = 28),
      chronic renal failure on hemodialysis (r = 0.784; P = 0.0003; n = 16),
      hypoparathyroidism (r = 0.950; P = 0.0001; n = 11), and pseudohypoparathyroidism
      (r = 0.987; P = 0.130; n = 4). Serum beta-CTx decreased by 47.4% +/- 8.8% (mean
      +/- SD) and 60.7% +/- 6.5% at 3 and 6 months, respectively, after initiation of
      estrogen replacement therapy in 34 women. These decreases were greater than the
      decreases in urinary excretion of deoxypyridinoline (31.8% +/- 3.9% and 38.1% +/-
      4.4%, respectively) or pyridinoline cross-linked C-terminal telopeptide of type I
      collagen (15.9% +/- 3.9% and 16.9% +/- 4.6%, respectively). CONCLUSIONS: The
      Elecsys beta-CrossLaps serum assay provides a potentially useful tool for
      assessing bone resorption state, including its response to estrogen replacement
      therapy.

PMID- 11468231
TI  - Discrimination of prostate cancer from benign disease by plasma measurement of
      intact, free prostate-specific antigen lacking an internal cleavage site at
      Lys145-Lys146.
AB  - BACKGROUND: The proportion of free prostate-specific antigen (PSA) is higher in
      the sera of patients with benign prostatic hyperplasia compared with patients
      with prostate cancer (PCa). We developed an immunoassay that measures intact,
      free PSA forms (fPSA-I), but does not detect free PSA that has been internally
      cleaved at Lys145-Lys146 (fPSA-N), and investigated whether this form could
      discriminate patients with PCa from those without PCa. METHODS: The assay for
      fPSA-I uses a novel monoclonal antibody (MAb) that does not detect PSA that has
      been internally cleaved at Lys145-Lys146. A MAb specific for free PSA was used as
      a capture antibody, and purified recombinant proPSA was used as a calibrator. The
      concentrations of fPSA-I, free PSA (PSA-F), and total PSA (PSA-T) were analyzed
      in EDTA-plasma samples (n = 276) from patients who participated in a screening
      program for PCa (PSA-T, 0.83-76.3 microg/L). RESULTS: The detection limit of the
      fPSA-I assay was 0.035 microg/L. Both the measured concentrations of fPSA-I and
      the concentrations of fPSA-N (calculated as PSA-F - fPSA-I) provided
      statistically significant discrimination of the two clinical groups. By contrast,
      PSA-F did not discriminate between these groups. Each of the ratios fPSA-I/PSA-F,
      fPSA-N/PSA-T, and PSA-F/PSA-T separated cancer samples from noncancer samples in
      a statistically significant manner (P <0.0001). The ratio fPSA-I/PSA-F was
      significantly higher in cancer (median, 59%) compared with noncancer samples
      (47%). CONCLUSIONS: The ratio fPSA-I/PSA-F is significantly higher in cancer
      compared with noncancer. The percentages of both fPSA-N/PSA-T and fPSA-I/PSA-F
      may provide interesting diagnostic enhancements alone or in combination with
      other markers and require further studies.

PMID- 11468232
TI  - Spectrophotometric microassay for delta-aminolevulinate dehydratase in dried
      blood spots as confirmation for hereditary tyrosinemia type I.
AB  - BACKGROUND: Hereditary tyrosinemia type I (HT) fulfills the criteria for
      inclusion in neonatal screening programs, but measurement of tyrosine lacks
      clinical specificity and quantitative assay of succinylacetone is laborious. We
      developed a semiquantitative assay based on inhibition of delta-aminolevulinate
      dehydratase (ALA-D) by succinylacetone. METHODS: Preincubation of 3-mm discs from
      dried-blood spots and reaction of the enzyme with delta-aminolevulinic acid as
      substrate were performed in microtiter plates. After separation of the
      supernatant and 10 min of color reaction with modified Ehrlich reagent, the
      formation of porphobilinogen was measured at 550 nm in a plate reader. RESULTS:
      The detection limit for succinylacetone was 0.3 micromol/L; imprecision (CV) was
      <5.5% within-run and 10-16% between-run. Storage of blood spots at ambient
      temperature for several days led to a significant decrease of ALA-D activity.
      Enzyme activity was lost in filter cards at 45 degrees C, but remained stable at
      2-37 degrees C. Enzyme activity was decreased in EDTA blood. The absorbance at
      550 nm was 0.221 (+/- 0.073) in healthy neonates and 0.043-0.100 in 11 patients
      with HT. All neonates with increased tyrosine (above the 99.5th centile) in
      neonatal screening (97 of 47 000) had normal results by the new assay.
      CONCLUSIONS: The spectrophotometric microassay for ALA-D is a simple and
      sensitive test for HT. This represents a basis for further examination of its
      general reliability as a confirmatory test if tyrosine is found to be increased.

PMID- 11468233
TI  - Plasma homocysteine is not subject to seasonal variation.
AB  - BACKGROUND: Studies investigating the relationship between plasma total
      homocysteine (tHcy) and vascular disease usually rely on a single measurement.
      Little information is available, however, on the seasonal variability of plasma
      tHcy. The aim of this study was to investigate the seasonal variation in fasting
      plasma tHcy and related B-vitamin intake and status in a group of people who did
      not consume fortified foods or take B-vitamin supplements. METHODS: In this
      longitudinal study, a group of 22 healthy people were followed for 1 year. A
      fasting blood sample and dietary information were collected from each individual
      every 3 months, i.e., at the end of each season. RESULTS: There was no
      significant seasonal variation in plasma tHcy or in B-vitamin intake or status
      with the exception of red cell folate (significantly lower in spring compared
      with autumn or winter) and serum folate (significantly lower in spring compared
      with the other seasons). Although the between-person variation in plasma tHcy was
      high (47%), the within-person variation was low (11%). This low variation,
      combined with the low methodologic imprecision of 3.8%, yielded a high
      reliability coefficient for plasma tHcy (0.97). CONCLUSIONS: Although there was a
      small seasonal variation in folate status, there was no corresponding seasonal
      variation in plasma tHcy. The high reliability coefficient for plasma tHcy
      suggests that a single measurement is reflective of an individual's average
      plasma tHcy concentration, thus indicating its usefulness as a potential
      predictor of disease. This, however, needs to be confirmed in different subgroups
      of the population.

PMID- 11468234
TI  - Sensitive and rapid quantification of busulfan in small plasma volumes by liquid
      chromatography-electrospray mass spectrometry.
AB  - BACKGROUND: High-dose busulfan is widely used in conditioning regimens before
      hematopoietic stem cell transplantation in both adults and children. Large
      interindividual variability in pharmacokinetics after oral administration has
      been reported; therefore, therapeutic drug monitoring of busulfan may decrease
      the incidence of drug-related toxicity (for example, hepatic venoocclusive
      disease) and may also improve therapeutic efficacy. METHODS: Busulfan
      concentrations were quantified using 200 microL of plasma and liquid-liquid
      extraction with diethyl ether after the addition of [2H8]busulfan as the internal
      standard. Separation and detection of busulfan and [2H8]busulfan were achieved
      with a LUNA C8 column (5 microm; 150 x 2 mm i.d.) at 30 degrees C, a HP 1100
      liquid chromatography system, and a HP 1100 single-quadrupole mass spectrometer.
      Busulfan and [2H8]busulfan were detected as ammonium adducts in selected-ion
      monitoring mode at m/z 264.2 and 272.2, respectively. RESULTS: The calibration
      curve was linear at 5-2000 microg/L busulfan. Intra- and interassay imprecision
      (CV) and bias were both <11%. The limits of detection and quantification were 2
      and 5 microg/L, respectively. Extraction recovery of busulfan was >87%. Analysis
      of pharmacokinetics in four patients receiving high-dose busulfan indicated that
      minimum busulfan concentrations before the next dose were 405-603 microg/L, with
      no interference observed. CONCLUSIONS: The new rapid and sensitive liquid
      chromatographic-mass spectrometric assay is an appropriate method for
      quantification of busulfan in human plasma, making therapeutic drug monitoring of
      busulfan faster and easier in clinical practice.

PMID- 11468235
TI  - Interlaboratory variation of biochemical markers of bone turnover.
AB  - BACKGROUND: Biochemical markers of bone metabolism are used to assess skeletal
      turnover, but the variability of marker assays is still an issue of practical
      concern. We describe the results of an international proficiency testing program
      for biochemical bone markers among clinical laboratories. METHODS: Two serum and
      two urine pools (normal and increased marker concentrations) were sent on dry ice
      to 79 laboratories for analysis within 2 weeks of receipt. RESULTS: Data were
      submitted by 73 laboratories. The within-method interlaboratory CVs (CV(IL)s)
      were as follows: serum bone-specific alkaline phosphatase (n = 47 laboratories),
      16-48%; serum osteocalcin (n = 31), 16-42%; urinary free deoxypyridinoline (n =
      30), 6.4-12%; urinary total deoxypyridinoline and pyridinoline (n = 29), 27-28%;
      urinary N-terminal cross-linked telopeptide of type I collagen (n = 10), 39%;
      serum C-terminal cross-linked telopeptide of type I collagen (ICTP; n = 8), 22
      27%; urinary hydroxyproline (n = 13), 12%. Analytical results showed both
      systematic and nonsystematic deviations. In identical samples, results obtained
      for the same marker by the same method differed up to 7.3-fold. In urine-based
      assays, correction for urinary creatinine slightly increased CVs. CONCLUSION:
      Even with identical assays and methods, results for most biochemical markers of
      bone turnover differ markedly among laboratories.

PMID- 11468236
TI  - Simultaneous multianalyte ELISA performed on a microarray platform.
AB  - BACKGROUND: A logical progression of the widely used microtiter plate ELISA is
      toward a protein array format that allows simultaneous detection of multiple
      analytes at multiple array addresses within a single well. Here we describe the
      construction and use of such a multiplex ELISA to measure prostate-specific
      antigen (PSA), alpha1-antichymotrypsin-bound PSA (PSA-ACT), and interleukin-6 (IL
      6). METHODS: We silanized glass plates and printed the appropriate capture
      antibodies to allow for the construction of "sandwich" ELISA quantification
      assays. We examined specificity of the assay for appropriate antigen, assembled
      calibration curves, and obtained PSA concentrations for 14 human serum samples.
      We compared the serum PSA concentrations derived through the use of our array
      with values obtained independently using a standard ELISA method. RESULTS: R2
      values generated by our microarray for the PSA and PSA-ACT calibration curves
      were 0.989 and 0.979, respectively. Analyte concentrations used for the
      construction of these curves were 0.31-20 microg of protein/L of diluent. IL-6
      calibration curve concentrations were 4.9-300 ng of IL-6/L of diluent. The R2
      value for the IL-6 calibration curve was 0.983. The 14 human serum samples
      screened by this micro-ELISA technique for PSA concentrations generated a
      regression equation (linear) with a slope of 0.83 +/- 0.10 and intercept of 0.74
      +/- 0.70 (R2 = 0.88). CONCLUSIONS: Multiplexed ELISA arrays are a feasible option
      for analyte quantification in complex biologic samples.

PMID- 11468237
TI  - Excitatory amino acids in cerebrospinal fluid of patients with acute head
      injuries.
AB  - BACKGROUND: The excitatory amino acids (EAAs) glutamate (Glu) and aspartate (Asp)
      play a role in the pathogenesis of postischemic and posttraumatic brain insult.
      The changes of EAAs in cerebrospinal fluid (CSF) of patients with traumatic brain
      injury are incompletely understood. METHODS: We used reversed-phase HPLC with
      precolumn derivatization with o-phthalaldehyde and fluorescence detection to
      measure Glu and Asp in CSF of 42 patients with acute head injury and 9 control
      adults without neurologic diseases. We assessed the Glasgow Coma Scale (GCS) on
      admission, the main lesion patterns on computed tomography (CT) scan within 24 h
      post trauma, and the Glasgow Outcome Scale (GOS) 3 months post injury. RESULTS:
      The mean concentrations of Glu and Asp in CSF in the brain-injured group were
      significantly higher than those of the control group (Glu, P <0.001; Asp, P
      <0.05). In patients admitted within 24 h after severe injury (n = 13), peak Glu
      values appeared within 48 h in 11 patients (85%), and the mean value remained
      higher than control values at day 7 (P <0.02). The concentrations of EAAs were
      higher in patients with severe injuries (GCS < or =8) than in those with milder
      injuries (Glu, P <0.001; Asp, P <0.05). GCS and peak EAAs correlated negatively
      (Glu, rs = -0.5706, P <0.001; Asp, rs = -0.5503, P <0.001). The patients with
      focal brain contusion on initial CT scan (n = 8) had a significantly lower peak
      Glu value than the patients with other patterns (n = 8-15; P <0.02 to 0.001). The
      peak value of EAAs in the poor-outcome group (including severe disability,
      vegetative state, and death) was significantly higher than in the good-outcome
      group (good recovery and moderate disability; Glu, P <0.001; Asp, P <0.01); GOS
      was closely correlated to the EAA values (Glu, rs = 0.5737, P <0.001; Asp, rs =
      0.5470, P <0.001). CONCLUSIONS: The EAA concentrations in CSF increase after
      acute head injury and remain higher for at least 1 week post injury in severely
      injured patients. The more severe the trauma, the more obvious the excitotoxicity
      induced by EAAs and the worse the outcome.

PMID- 11468238
TI  - Stability of ascorbic acid in solutions stored in autosampler vials.

PMID- 11468239
TI  - Determination of iron metabolism-related reference values in a healthy adult
      population.

PMID- 11468240
TI  - Determination of blood total, reduced, and oxidized glutathione in pediatric
      subjects.

PMID- 11468241
TI  - Rapid analysis of mitochondrial DNA heteroplasmy in diabetes by gel-microchip
      electrophoresis.

PMID- 11468242
TI  - Do modifications of nonequimolar assays for total prostate-specific antigen
      improve detection of prostate cancer?

PMID- 11468243
TI  - Immuno-PCR assay for homodimeric osteoprotegerin.

PMID- 11468244
TI  - False-negative results in detection of monoclonal proteins by capillary zone
      electrophoresis: a prospective study.

PMID- 11468245
TI  - Microarray technology and applications: an all-language literature survey
      including books and patents.

PMID- 11468246
TI  - Analytical performance of a particle-enhanced nephelometric immunoassay for serum
      cystatin C using rate analysis.

PMID- 11468247
TI  - Quantification of mycophenolic acid in plasma samples collected during and
      immediately after intravenous administration of mycophenolate mofetil.

PMID- 11468248
TI  - Extracellular tyrosinase mRNA within apoptotic bodies is protected from
      degradation in human serum.

PMID- 11468249
TI  - Heterozygous M3Mmalton alpha1-antitrypsin deficiency associated with end-stage
      liver disease: case report and review.
AB  - Alpha1-antitrypsin (alpha1AT) deficiency is an autosomal recessive disorder that
      can cause pulmonary emphysema and liver disease. We report here the case of a 59
      year-old woman who was admitted to hospital for evaluation of jaundice. She had
      no history of hepatitis or childhood liver disease. She had never received a
      blood transfusion, nor had she abused drugs or alcohol. Transjugular liver biopsy
      was then performed and revealed a micronodular cirrhosis. Ten months later,
      because of persistent liver cell failure and ascites, she underwent an orthotopic
      liver transplantation. Investigation of alpha1AT system in the proband revealed a
      substantial decrease in serum alpha1AT associated with a low elastase inhibitory
      capacity. The Pi phenotype revealed a PiM-like profile. Sequencing of exons 1-5
      demonstrated the presence of the M3 allele. Moreover, a triple nucleotide
      deletion was detected in exon 2 of one allele. This caused an "in-phase"
      frameshift, coding for a protein deficient in a single Phe residue, which
      corresponded to the Mmalton variant. After liver biopsy, periodic acid-Schiff
      positive acidophilic bodies resistant to diastase digestion were observed in the
      cytoplasm of hepatocytes. These results demonstrated that our patient had a
      heterozygous M3Mmalton alpha1AT genotype related to a deficiency phenotype. This
      observation is the first of a patient with heterozygous Mmalton genotype
      associated with an alpha1AT deficiency that induced severe liver disease
      requiring orthotopic liver transplantation.

PMID- 11468250
TI  - Standardization of bone marker nomenclature.

PMID- 11468251
TI  - Biological variation of serum amyloid A in healthy subjects.

PMID- 11468252
TI  - Heptaminol interferes in the AxSYM FPIA amphetamine/methamphetamine II assay.

PMID- 11468253
TI  - Urinary sulfur compounds in Down syndrome.

PMID- 11468259
TI  - The clinician and laboratorian: dynamic transitions. Proceedings of The twenty
      fourth Arnold O. Beckman Conference in Clinical Chemistry. February 11-12, 2001.
      Newport Beach, California, USA.

PMID- 11468260
TI  - Laboratory adaptations--changing expectations.

PMID- 11468261
TI  - Integrated patient data for optimal patient management: the value of laboratory
      data in quality improvement.
AB  - Managed care organizations are shifting from traditional utilization management
      programs to focus on initiatives that improve the health of an insured
      population. This strategy requires sophisticated data integration to identify at
      risk individuals and track outcomes. Laboratory data are becoming increasingly
      valuable tools for managed care organizations and healthcare providers. The HEDIS
      Effectiveness of Care measures have incorporated laboratory data into several key
      performance indicators. By building a comprehensive repository of laboratory data
      that includes both procedure codes and laboratory values, managed care
      organizations can realize substantial savings by avoiding the costly medical
      record reviews required when administrative data are incomplete. In addition to
      tracking clinical outcomes, laboratory data provide the ability to risk-stratify
      a population to target high-risk individuals for case management and disease
      management interventions. Healthcare organizations face several challenges in the
      integration of laboratory data into medical databases and practice management
      software. Confidentiality is a key consideration in view of recent healthcare
      regulations. Providers of laboratory services should work collaboratively with
      organizations setting standards for healthcare informatics to facilitate the
      pooling of data for quality improvement and outcomes research. Health Level
      Seven, Inc. (HL7), Logical Observation Identifier Names and Codes (LOINC), and
      Systematized Nomenclature of Medicine (SNOMED) will likely play a key role in
      this process.

PMID- 11468262
TI  - Connectivity from source to action.
AB  - Recent advances in electronic connectivity technology make conceivable almost
      instantaneous movement of data from the patient or laboratory to any other point
      in the healthcare system. The Internet, combined with new standards for wireless
      data transmission, has erased many of the previous physical barriers. Interface
      engines and formatting/content standards have facilitated the connection of
      multiple disparate systems in medicine. However, major logical barriers persist,
      and overcoming these barriers is key to achieving functional connectivity. These
      include fundamental issues of patient safety (such as reliably identifying the
      patient), capture of the most clinically meaningful data (patient history,
      physical examination findings, physician diagnostic impressions, and full range
      of orders), unambiguous identification of data elements, and synchronization of
      control files among multiple different systems within the healthcare enterprise.
      Fortunately, tools exist to address each of these areas. This report cites
      illustrative examples of such tools.

PMID- 11468263
TI  - The total laboratory solution: a new laboratory E-business model based on a
      vertical laboratory meta-network.
AB  - Major forces are now reshaping all businesses on a global basis, including the
      healthcare and clinical laboratory industries. One of the major forces at work is
      information technology (IT), which now provides the opportunity to create a new
      economic and business model for the clinical laboratory industry based on the
      creation of an integrated vertical meta-network, referred to here as the "total
      laboratory solution" (TLS). Participants at the most basic level of such a
      network would include a hospital-based laboratory, a reference laboratory, a
      laboratory information system/application service provider/laboratory portal
      vendor, an in vitro diagnostic manufacturer, and a pharmaceutical/biotechnology
      manufacturer. It is suggested that each of these participants would add value to
      the network primarily in its area of core competency. Subvariants of such a
      network have evolved over recent years, but a TLS comprising all or most of these
      participants does not exist at this time. Although the TLS, enabled by IT and
      closely akin to the various e-businesses that are now taking shape, offers many
      advantages from a theoretical perspective over the current laboratory business
      model, its success will depend largely on (a) market forces, (b) how the
      collaborative networks are organized and managed, and (c) whether the network can
      offer healthcare organizations higher quality testing services at lower cost. If
      the concept is successful, new demands will be placed on hospital-based
      laboratory professionals to shift the range of professional services that they
      offer toward clinical consulting, integration of laboratory information from
      multiple sources, and laboratory information management. These information
      management and integration tasks can only increase in complexity in the future as
      new genomic and proteomics testing modalities are developed and come on-line in
      clinical laboratories.

PMID- 11468264
TI  - Overview of evidence-based medicine: challenges for evidence-based laboratory
      medicine.
AB  - Evidence-based medicine (EBM) has been driven by the need to cope with
      information overload, by cost-control, and by a public impatient for the best in
      diagnostics and treatment. Clinical guidelines, care maps, and outcome measures
      are quality improvement tools for the appropriateness, efficiency, and
      effectiveness of health services. Although they are imperfect, their value
      increases with the quality of the evidence they incorporate. Laboratory
      professionals must direct more effort to demonstrating the impact of laboratory
      tests on a greater variety of clinical outcomes. Laboratory and clinical
      practitioners must be familiar with many of the accessible electronic and paper
      tools for searching for evidence. Detailed statistical and epidemiologic
      knowledge is not essential, but critical appraisal skills and a competent
      understanding of the strengths and weaknesses of systematic review and
      metaanalysis are necessary. Overemphasis on complexity and failure to recognize
      time limitations are major barriers to translating EBM into everyday practice.
      Emphasizing and practicing the role of the laboratory professional as a skilled
      clinical consultant strongly grounded in evidence as well, in addition to better
      integration of laboratory and clinical information and improved laboratory
      reports will overcome most barriers. There is a poverty of good, primary studies
      of test evaluations. Institution of more consistent standards for the design and
      reporting of studies on diagnostic accuracy should improve the situation. If
      nothing else, systematic reviews have demonstrated the need for more good-quality
      primary research in laboratory medicine.

PMID- 11468265
TI  - Laboratory-related outcomes in healthcare.
AB  - Outcomes studies, long common on the therapeutic side of medicine, are appearing
      in the diagnostic arena. Outcomes can be defined as results of medical
      interventions (therapies or tests) in terms of health or cost. The studies of
      outcomes are important because funding for medical interventions increasingly
      depends on them; a major accrediting agency even defines "quality" entirely in
      terms of outcomes. The study of laboratory-related outcomes is complex. Multiple
      steps occur between testing and outcomes, physicians act unpredictably on test
      results, and outcomes studies have high costs relative to potential profit from
      the test. Study design often must specify the action that is to follow a test
      result. The model outcomes study is a randomized controlled trial (RCT). The
      CONSORT statement, which is used as a guideline for RCTs of therapies, is largely
      applicable to studies of diagnostic interventions. Recent laboratory-related RCTs
      have addressed questions such as: "Does routine testing before cataract surgery
      decrease morbidity or mortality?" and "Does fecal occult bleed testing decrease
      the incidence of colorectal cancer?" RCTs of tests are sometimes impractical.
      Other approaches include simulation modeling and the use of intervention and
      control periods of testing. As for RCTs, these approaches require careful
      attention to study design, data analysis, and interpretation and reporting of
      results.

PMID- 11468266
TI  - Molecular detection of Mycobacterium tuberculosis: impact on patient care.
AB  - BACKGROUND: Nucleic acid amplification technologies such as PCR are
      revolutionizing the detection of infectious pathogens such as tuberculosis (TB).
      Amplification technology offers the potential for the diagnosis of TB in a few
      hours with a high degree of sensitivity and specificity. However, molecular
      assays neither replace nor reduce the need for conventional smear and culture,
      speciation, and antibiotic sensitivity assays. METHODS: We undertook prospective
      studies of sputum samples to assess the performance of two PCR-based assays for
      the detection of TB as well as the impact of more rapid availability of test
      results on patient care. RESULTS: The sensitivity of both the in-house and
      Amplicor PCR assays was 100% for smear-positive sputa. For smear-negative sputa
      (two sputum samples collected during the first 24 h of hospitalization), the
      sensitivity was 85% for our in-house PCR assay and 74% for the Roche PCR assay.
      Approximately 10% of the smear- and culture-negative sputa yielded positive PCR
      results; however, more than one-half of these were positive with both the in
      house and Amplicor assays, suggesting the presence of TB DNA or organisms.
      Several of these came from patients whose other samples grew Mycobacterium
      tuberculosis during the same admission, and others came from patients who had
      previously treated TB. Overall, the specificities of the in-house and Amplicor
      PCR assays in smear-negative patients were 86% and 93%, respectively.
      CONCLUSIONS: Molecular detection of slow-growing pathogens such as M.
      tuberculosis have the potential to improve clinical care through a dramatic
      reduction in the time required for detection and may provide substantial savings
      in the overall cost of care of a patient compared with conventional smear,
      culture, and speciation alone, despite the fact that conventional assays must
      still be performed for speciation of nontuberculous mycobacteria and for full
      assessment of antibiotic sensitivity.

PMID- 11468267
TI  - Successful testing protocols in virology.
AB  - Molecular methods have had a significant impact on the diagnosis of viral
      infections because of their superior sensitivity and rapid turnaround time
      compared with conventional diagnostic methods. These characteristics have allowed
      molecular tests to play a central role in the use of testing protocols for
      managing viral infections. Several examples of such protocols are reviewed in
      this report, including the use of molecular testing for early disease detection
      to improve overall disease management and to direct antiviral therapy.

PMID- 11468268
TI  - Guidelines and algorithms: perceptions of why and when they are successful and
      how to improve them.
AB  - Medicine is increasingly complex, a reality created by the explosion of knowledge
      during the last 50 years. The cost of applying this knowledge creates a daunting
      economic challenge. As a result, there has been a profusion of guidelines
      intended to influence medical practice. This report explores the interrelated
      issues and concepts that impact the value and success of guidelines. These
      include medical quality and error, compliance, and the impact on outcomes in an
      evidence-based medicine context. Lessons learned from previous guidelines must be
      understood in relation to human behavior. Legal implications of the guidelines
      must be considered because both an increase and a decrease in liability can be
      anticipated. Many products have been labeled "advocacy guidelines" with a
      negative context. They are believed to express motivation rather than optimizing
      care. The ideal of professionalism is challenged, and there is potential for the
      growing use of guidelines in enforcing punitive actions. Constructive experience
      has emphasized the appropriate required elements for practice guidelines: a
      systematic review of the literature, an assessment of the volume and level of the
      evidence, and development of a review process by an appropriate multidisciplinary
      group for consistency, clinical impact, and resource implications leading to
      clearly stated and reasonable recommendations. The dissemination of guidelines,
      beyond conventional publication in a journal, will impact the success of the
      intended outcomes. The exploitation of electronic avenues, including the Internet
      and the evolving interactive electronic medical record, seems to be essential for
      future success in these endeavors.

PMID- 11468270
TI  - Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to
      Huntington's disease (HD) transcripts and is activated in HD tissue.
AB  - Fourteen neurological diseases have been associated with the expansion of
      trinucleotide repeat regions. These diseases have been categorized into those
      that give rise to the translation of toxic polyglutamine proteins and those that
      are untranslated. Thus far, compelling evidence has not surfaced for the
      inclusion of a model in which a common mechanism may participate in the
      pathobiology of both translated and untranslated trinucleotide diseases. In these
      studies we show that a double-stranded RNA-binding protein, PKR, which has
      previously been linked to virally-induced and stress-mediated apoptosis,
      preferentially binds mutant huntingtin RNA transcripts immobilized on
      streptavidin columns that have been incubated with human brain extracts. These
      studies also show, by immunodetection in tissue slices, that PKR is present in
      its activated form in both human Huntington autopsy material and brain tissue
      derived from Huntington yeast artificial chromosome transgenic mice. The
      increased immunolocalization of the activated kinase is more pronounced in areas
      most affected by the disease and, coupled with the RNA binding results, suggests
      a role for PKR activation in the disease process.

PMID- 11468271
TI  - Disease-causing missense mutations in the PHEX gene interfere with membrane
      targeting of the recombinant protein.
AB  - PHEX is homologous to the M13 zinc metallopeptidases, a class of type II membrane
      glycoproteins. Although more than 140 mutations in the PHEX gene have been
      identified in patients with X-linked hypophosphatemia (XLH), the most prevalent
      form of inherited rickets, the molecular consequences of disease-causing PHEX
      mutations have not yet been investigated. We examined the effect of PHEX missense
      mutations on cellular trafficking of the recombinant protein. Four mutant PHEX
      cDNAs were generated by PCR mutagenesis: C85R, G579R and S711R, identified in XLH
      patients, and E581V, previously engineered in neutral endopeptidase 24.11, where
      it abolished catalytic activity but not plasma membrane targeting. Wild-type and
      mutant PHEX cDNAs were transfected in HEK(293) cells and PHEX protein expression
      was characterized. In contrast to the wild-type and E581V PHEX proteins, the
      C85R, G579R and S711R mutants were completely sensitive to endoglycosidase H
      digestion, indicating that they were not fully glycosylated. Sequestration of the
      disease-causing mutant proteins in the endoplasmic reticulum (ER) and plasma
      membrane localization of wild-type and E581V PHEX proteins was demonstrated by
      immunofluorescence and cell surface biotinylation. Of the three mutant PHEX
      proteins, the S711R was the least stable and the only one that could be rescued
      from the ER to the plasma membrane in cells grown at 26 degrees C. The chemical
      chaperone glycerol failed to correct defective targeting of all three mutant
      proteins. Our data provide a mechanism for loss of PHEX function in XLH patients
      expressing the C85R, G579R and S711R mutations.

PMID- 11468272
TI  - Antisense-induced exon skipping restores dystrophin expression in DMD patient
      derived muscle cells.
AB  - Due to frame-shifting mutations in the DMD gene that cause dystrophin deficiency,
      Duchenne muscular dystrophy (DMD) patients suffer from lethal muscle
      degeneration. In contrast, mutations in the allelic Becker muscular dystrophy
      (BMD) do not disrupt the translational reading frame, resulting in a less severe
      phenotype. In this study, we explored a genetic therapy aimed at restoring the
      reading frame in muscle cells from DMD patients through targeted modulation of
      dystrophin pre-mRNA splicing. Considering that exon 45 is the single most
      frequently deleted exon in DMD, whereas exon (45+46) deletions cause only a mild
      form of BMD, we set up an antisense-based system to induce exon 46 skipping from
      the transcript in cultured myotubes of both mouse and human origin. In myotube
      cultures from two unrelated DMD patients carrying an exon 45 deletion, the
      induced skipping of exon 46 in only approximately 15% of the mRNA led to normal
      amounts of properly localized dystrophin in at least 75% of myotubes. Our results
      provide first evidence of highly effective restoration of dystrophin expression
      from the endogenous gene in DMD patient-derived muscle cells. This strategy may
      be applicable to not only >65% of DMD mutations, but also many other genetic
      diseases.

PMID- 11468273
TI  - Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant
      retinitis pigmentosa (RP13).
AB  - Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized
      by progressive degeneration of the peripheral retina leading to night blindness
      and loss of visual fields. With an incidence of approximately 1 in 4000, RP can
      be inherited in X-linked, autosomal dominant or autosomal recessive modes. The
      RP13 locus for autosomal dominant RP (adRP) was placed on chromosome 17p13.3 by
      linkage mapping in a large South African adRP family. Using a positional cloning
      and candidate gene strategy, we have identified seven different missense
      mutations in the splicing factor gene PRPC8 in adRP families. Three of the
      mutations cosegregate within three RP13 linked families including the original
      large South African pedigree, and four additional mutations have been identified
      in other unrelated adRP families. The seven mutations are clustered within a 14
      codon stretch within the last exon of this large 7 kb transcript. The altered
      amino acid residues at the C-terminus exhibit a high degree of conservation
      across species as diverse as humans, Arabidopsis and trypanosome, suggesting that
      some functional significance is associated with this part of the protein. These
      mutations in this ubiquitous and highly conserved splicing factor offer
      compelling evidence for a novel pathway to retinal degeneration.

PMID- 11468274
TI  - Processing of beta-dystroglycan by matrix metalloproteinase disrupts the link
      between the extracellular matrix and cell membrane via the dystroglycan complex.
AB  - The dystroglycan complex is a membrane-spanning complex composed of two subunits,
      alpha- and beta-dystroglycan. alpha-dystroglycan is a cell surface peripheral
      membrane protein which binds to the extracellular matrix (ECM), whereas beta
      dystroglycan is an integral membrane protein which anchors alpha-dystroglycan to
      the cell membrane. The dystroglycan complex provides a tight link between the ECM
      and cell membrane. Dysfunction of the dystroglycan complex has commonly been
      implicated in the molecular pathogenesis of severe forms of hereditary
      neuromuscular diseases, including Duchenne muscular dystrophy, Fukuyama-type
      congenital muscular dystrophy and sarcoglycanopathy (LGMD2C, -D, -E and -F). To
      begin to clarify the pathway by which the dysfunction of the dystroglycan complex
      could lead to muscle cell degeneration, we investigated the proteolytic
      processing of the dystroglycan complex in this study. We demonstrate that (i) a
      30 kDa fragment of beta-dystroglycan is expressed in peripheral nerve, kidney,
      lung and smooth muscle, but not skeletal muscle, cardiac muscle or brain, and
      (ii) this fragment is the product of proteolytic processing of the extracellular
      domain of beta-dystroglycan by the membrane-associated matrix metalloproteinase
      (MMP) activity. Importantly, furthermore, we demonstrate that this processing
      disintegrates the dystroglycan complex. Our results indicate that the processing
      of beta-dystroglycan by MMP causes the disruption of the link between the ECM and
      cell membrane via the dystroglycan complex, which could have profound effects on
      cell viability. Based on these and previously reported findings, we propose a
      hypothesis that this processing may play a crucial role in the molecular
      pathogenesis of sarcoglycanopathy.

PMID- 11468275
TI  - Temporal and spatial expression patterns of the CRX transcription factor and its
      downstream targets. Critical differences during human and mouse eye development.
AB  - Cone--rod homeobox (CRX), a paired-like homeobox transcription factor, plays a
      major role in photoreceptor development and maintenance of the retina. Fifteen
      different mutations in the CRX gene have been identified as a cause of blinding
      retinal dystrophy. As a step towards characterizing the underlying
      pathophysiology of disease, temporal and spatial gene expression patterns during
      human and mouse eye development were investigated for CRX and for downstream
      retinally expressed genes, postulated to be transactivated by CRX. We found that
      human CRX was expressed at 10.5 weeks post-conception (p.c.). This was
      significantly later than observed in mouse development. Immunocytochemistry in
      human retina showed that CRX protein was not detected until >4 weeks later at 15
      weeks p.c., implying that it would be unable to transactivate PDEB, IRBP and
      arrestin, which were all expressed before 15 weeks. These data therefore
      eliminate CRX as the major transcriptional activator of these three genes from a
      wide group of retinal genes that can be transactivated by CRX in vitro.
      Additionally, PDEB was expressed 2 weeks before CRX whereas murine Pdeb was
      expressed after Crx, highlighting a potential difference for the role of PDEB in
      human eye development. Previous data had shown CRX expression in the adult human
      retina to be photoreceptor-specific; however, we demonstrate that this gene is
      also expressed in the inner nuclear layer (INL) of the human and mouse retina by
      in situ hybridization and immunocytochemistry. INL localization of murine Crx was
      confirmed in rd/rd,cl mice, as in this mouse model the photoreceptors are absent.
      We have found important differences in the temporal expression of this gene in
      human and mouse retina, although spatial expression of the CRX gene appears to be
      conserved. In addition, downstream targets of CRX in vitro might not represent in
      vivo function during development. These data support concerns about the extent to
      which we can extrapolate from rodent models regarding embryonic development and
      disease pathophysiology.

PMID- 11468276
TI  - A specific promoter of the sensory cells of the inner ear defined by
      transgenesis.
AB  - To date, no promoter sequence specific to the inner ear sensory cells (hair
      cells) has been reported. In an effort to understand the molecular mechanisms
      that determine hair cell fate in the inner ear, and with the goal of developing a
      valuable tool for gene therapy and for the generation of conditional knockouts,
      we initiated a search for cis-acting DNA sequences that regulate the expression
      of the murine Myo7a and human MYO7A genes. These genes encode the unconventional
      myosin VIIA which is expressed in hair cells and in some other epithelial cells.
      We generated lines of transgenic mice expressing the green fluorescent protein
      (GFP ) reporter gene under the control of several 5'-truncated versions of the
      Myo7a/MYO7A promoter region and intron 1. We obtained transgenic mice with a GFP
      expression restricted to the hair cells of the inner ear, cochlea and vestibule.
      Successive deletions of the promoter allowed us to define a minimal sequence of
      118 bp that is sufficient, in the presence of intron 1, to target the transgene
      expression to hair cells. In addition, the deletion of intron 1 from the
      transgenes abolished hair cell expression, thus indicating the presence of a
      strong enhancer in the intron. This is the first report of regulatory sequences
      sufficient to target the expression of a gene exclusively in sensory cells of the
      inner ear. It also opens up the possibility for the analysis of the hair cell
      transcriptome.

PMID- 11468277
TI  - Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus
      (BPES) families demonstrates a genotype--phenotype correlation.
AB  - Mutations in FOXL2, a forkhead transcription factor gene, have recently been
      shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types
      I and II, a rare genetic disorder. In BPES type I a complex eyelid malformation
      is associated with premature ovarian failure (POF), whereas in BPES type II the
      eyelid defect occurs as an isolated entity. In this study, we describe the
      identification of novel mutations in the FOXL2 gene in BPES types I and II
      families, in sporadic BPES patients, and in BPES families where the type could
      not be established. In 67% of the patients studied, we identified a mutation in
      the FOXL2 gene. In total, 21 mutations (17 of which are novel) and one
      microdeletion were identified. Thirteen of these FOXL2 mutations are unique. In
      this study, we demonstrate that there is a genotype--phenotype correlation for
      either types of BPES by the finding that mutations predicted to result in a
      truncated protein either lacking or containing the forkhead domain lead to BPES
      type I. In contrast, duplications within or downstream of the forkhead domain,
      and a frameshift downstream of them, all predicted to result in an extended
      protein, cause BPES type II. In addition, in 30 unrelated patients with isolated
      POF no causal mutations were identified in FOXL2. Our study provides further
      evidence that FOXL2 haploinsufficiency may cause BPES types I and II by the
      effect of a null allele and a hypomorphic allele, respectively. Furthermore, we
      propose that in a fraction of the BPES patients the genetic defect does not
      reside within the coding region of the FOXL2 gene and may be caused by a position
      effect.

PMID- 11468278
TI  - Distant cis-elements regulate imprinted expression of the mouse p57( Kip2)
      (Cdkn1c) gene: implications for the human disorder, Beckwith--Wiedemann syndrome.
AB  - Complex phenotypes and genotypes characterize the human disease, Beckwith-
      Wiedemann syndrome (BWS). Genetic and epigenetic mutations are found in five
      different genes which all lie within a 1 Mb imprinted domain on human chromosome
      11p15. Only two of these genes, p57(KIP2) (CDKN1C) and IGF2, are likely to be
      functionally involved in this disease. The presence of the additional mutations
      therefore suggests a role for the regulation of these two genes by distant cis
      elements. The mouse Igf2 gene is regulated by enhancers and imprinting elements
      which lie >120 kb downstream of its promoter. Here we show that key elements for
      expression of the mouse p57(Kip2) (Cdkn1c) gene also lie at a distance. Enhancers
      for expression within skeletal muscle and cartilage lie >25 kb downstream of the
      gene. In addition, we find no evidence for allele-specific expression of
      p57(Kip2) (Cdkn1c) from our bacterial artificial chromosome transgenes that span
      315 kb around the locus. This suggests that a key imprinting element for
      p57(Kip2) (Cdkn1c) also lies at a distance. Therefore, BWS in humans may result
      from disruption of appropriate expression of the p57(KIP2) (CDKN1C) gene through
      mutations that occur at a substantial distance from the gene.

PMID- 11468279
TI  - Chromosome 1 loci in Finnish schizophrenia families.
AB  - We have earlier reported evidence for linkage to two regions on chromosome 1q32-
      q42 in schizophrenia families collected for two separate studies in Finland. Here
      we report the results of a fine mapping effort aimed at further definition of the
      chromosomal region of interest using a large, population-based study sample (221
      families, 557 affected individuals). Most affecteds (78%) had a DSM-IV
      schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders.
      We genotyped a total of 147 microsatellite markers on a wide 45 cM region of
      chromosome 1q. The results were analyzed separately for families originating from
      an internal isolate of Finland and for families from the rest of Finland, as well
      as for all families jointly. We used traditional two-point linkage analysis,
      SimWalk2 multipoint analysis and a novel gamete-competition association/linkage
      method. Evidence for linkage was obtained for one locus in the combined sample
      (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal
      isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the
      strongest evidence for linkage was obtained with markers located 22 cM
      centromeric from this marker (Z(max) = 2.30, D1S245). Multipoint analysis also
      indicated these loci. Some evidence for association with several markers was
      observed using the gamete-competition method. Interestingly, the strongest
      evidence for linkage in the combined study sample was obtained for marker
      D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as
      a susceptibility gene for schizophrenia. These results are consistent with the
      presence of susceptibility gene(s) in this chromosomal region, a result also
      implied in other recent family studies of schizophrenia.

PMID- 11468280
TI  - Fibroblasts in mechanically stressed collagen lattices assume a "synthetic"
      phenotype.
AB  - Fibroblasts are subjected to changes of the mechanical force balance during
      physiological as well as pathological situations, such as wound healing,
      development of hypertrophic scars, and fibrogenesis. However, the molecular
      response and the changes in fibroblast gene expression upon mechanical
      stimulation remain poorly understood. As an in vitro model, human dermal
      fibroblasts were cultured within a three-dimensional network of fibrillar
      collagen either under high (stressed) or low tension (relaxed). cDNA microarray
      technology in combination with Northern blot analysis led to identification of
      mechano-responsive genes coding for extracellular matrix proteins, fibrogenic
      growth factors, protease inhibitors, components of focal adhesions, and the
      cytoskeleton. Application of biaxial strain to fibroblasts cultured on flexible
      silicone membranes revealed that the type of strain as well as the properties of
      the substrate induced different patterns of gene regulation. The transcriptional
      profile of mechanically induced genes in collagen lattices suggests that
      mechanical stimuli lead to a "synthetic" fibroblast phenotype characterized by
      induction of connective tissue synthesis while simultaneously inhibiting matrix
      degradation.

PMID- 11468281
TI  - Alkylsulfonates as probes of uncoupling protein transport mechanism. Ion pair
      transport demonstrates that direct H(+) translocation by UCP1 is not necessary
      for uncoupling.
AB  - The mechanism of fatty acid-dependent uncoupling by mitochondrial uncoupling
      proteins (UCP) is still in debate. We have hypothesized that the anionic fatty
      acid head group is translocated by UCP, and the proton is transported
      electroneutrally in the bilayer by flip-flop of the protonated fatty acid.
      Alkylsulfonates are useful as probes of the UCP transport mechanism. They are
      analogues of fatty acids, and they are transported by UCP1, UCP2, and UCP3. We
      show that undecanesulfonate and laurate are mutually competitive inhibitors,
      supporting the hypothesis that fatty acid anion is transported by UCP1.
      Alkylsulfonates cannot be protonated because of their low pK(a), consequently,
      they cannot catalyze electroneutral proton transport in the bilayer and cannot
      support uncoupling by UCP. We report for the first time that propranolol forms
      permeant ion pairs with the alkylsulfonates, thereby removing this restriction.
      Because a proton is transported with the neutral ion pair, the sulfonate is able
      to deliver protons across the bilayer, behaving as if it were a fatty acid. When
      ion pair transport is combined with UCP1, we now observe electrophoretic proton
      transport and uncoupling of brown adipose tissue mitochondria. These experiments
      confirm that the proton transport of UCP-mediated uncoupling takes place in the
      lipid bilayer and not via UCP itself. Thus, UCP1, like other members of its gene
      family, translocates anions and does not translocate protons.

PMID- 11468282
TI  - Human glutathione transferase A1-1 demonstrates both half-of-the-sites and all-of
      the-sites reactivity.
AB  - A study of the kinetics of a heterodimeric variant of glutathione transferase
      (GST) A1-1 has led to the conclusion that, although the wild-type enzyme displays
      all-of-the-sites reactivity in nucleophilic aromatic substitution reactions, it
      demonstrates half-of-the-sites reactivity in addition reactions. The heterodimer,
      designed to be essentially catalytically inactive in one subunit due to a single
      point mutation (D101K), and the two parental homodimers were analyzed with seven
      different substrates, exemplifying three types of reactions catalyzed by
      glutathione transferases (nucleophilic aromatic substitution, addition, and
      double-bond isomerization reactions). Stopped-flow kinetic results suggested that
      the wild-type GST A1-1 behaved with half-of-the-sites reactivity in a
      nucleophilic aromatic substitution reaction, but steady-state kinetic analyses of
      the GST A1-D101K heterodimer revealed that this was presumably due to changes to
      the extinction coefficient of the enzyme-bound product. In contrast, steady-state
      kinetic analysis of the heterodimer with three different substrates of addition
      reactions provided evidence that the wild-type enzyme displayed half-of-the-sites
      reactivity in association with these reactions. The half-of-the-sites reactivity
      was shown not to be dependent on substrate size, the level of saturation of the
      enzyme with glutathione, or relative catalytic rate.

PMID- 11468283
TI  - Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic
      spines via its N terminus.
AB  - The consequences of the rapid 3-phosphorylation of inositol 1,4,5-trisphosphate
      (IP(3)) to produce inositol 1,3,4,5-tetrakisphosphate (IP(4)) via the action of
      IP(3) 3-kinases involve the control of calcium signals. Using green fluorescent
      protein constructs of full-length and truncated IP(3) 3-kinase isoform A
      expressed in HeLa cells, COS-7 cells, and primary neuronal cultures, we have
      defined a novel N-terminal 66-amino acid F-actin-binding region that localizes
      the kinase to dendritic spines. The region is necessary and sufficient for
      binding F-actin and consists of a proline-rich stretch followed by a predicted
      alpha-helix. We also localized endogenous IP(3) 3-kinase A to the dendritic
      spines of pyramidal neurons in primary hippocampal cultures, where it is co
      localized postsynaptically with calcium/calmodulin-dependent protein kinase II.
      Our experiments suggest a link between inositol phosphate metabolism, calcium
      signaling, and the actin cytoskeleton in dendritic spines. The phosphorylation of
      IP(3) in dendritic spines to produce IP(4) is likely to be important for
      modulating the compartmentalization of calcium at synapses.

PMID- 11468284
TI  - Identification of ligand-binding site III on the immunoglobulin-like domain of
      the granulocyte colony-stimulating factor receptor.
AB  - The granulocyte colony-stimulating factor receptor (G-CSF-R) forms a tetrameric
      complex with G-CSF containing two ligand and two receptor molecules. The N
      terminal Ig-like domain of the G-CSF-R is required for receptor dimerization, but
      it is not known whether it binds G-CSF or interacts elsewhere in the complex.
      Alanine scanning mutagenesis was used to show that residues in the Ig-like domain
      of the G-CSF-R (Phe(75), Gln(87), and Gln(91)) interact with G-CSF. This binding
      site for G-CSF overlapped with the binding site of a neutralizing anti-G-CSF-R
      antibody. A model of the Ig-like domain showed that the binding site is very
      similar to the viral interleukin-6 binding site (site III) on the Ig-like domain
      of gp130, a related receptor. To further characterize the G-CSF-R complex,
      exposed and inaccessible regions of monomeric and dimeric ligand-receptor
      complexes were mapped with monoclonal antibodies. The results showed that the E
      helix of G-CSF was inaccessible in the dimeric but exposed in the monomeric
      complex, suggesting that this region binds to the Ig-like domain of the G-CSF-R.
      In addition, the N terminus of G-CSF was exposed to antibody binding in both
      complexes. These data establish that the dimerization interface of the complete
      receptor complex is different from that in the x-ray structure of a partial
      complex. A model of the tetrameric G-CSF.G-CSF-R complex was prepared, based on
      the viral interleukin-6.gp130 complex, which explains these and previously
      published data.

PMID- 11468285
TI  - Cysteine substitutions reveal dual functions of the amino-terminal tail in cystic
      fibrosis transmembrane conductance regulator channel gating.
AB  - Previously, we observed that the cystic fibrosis transmembrane conductance
      regulator (CFTR) channel openings are destabilized by replacing several acidic
      residues in the amino-terminal tail with alanines (Naren, A. P., Cormet-Boyaka,
      E., Fu, J., Villain, M., Blalock, J. E., Quick, M. W., and Kirk, K. L. (1999)
      Science 286, 544-548). Here we determined whether this effect is due to the loss
      of negative charge at these sites and whether the amino-terminal tail also
      modulates other aspects of channel gating. We introduced cysteines at two of
      these positions (E54C/D58C) and tested a series of methanethiosulfonate (MTS)
      reagents for their effects on the gating properties of these cysteine mutants in
      intact Xenopus oocytes and excised membrane patches. Covalent modification of
      these sites with either neutral (MMTS) or charged (2
      carboxyethylmethanethiosulfonate (MTSCE) and 2
      (trimethylammonium)ethylmethanethiosulfonate (MTSET)) reagents markedly inhibited
      channel open probability primarily by reducing the rate of channel opening. The
      MTS reagents had negligible effects on the gating of the wild type channel or a
      corresponding double alanine mutant (E54A/D58A) under the same conditions. The
      inhibition of the opening rate of the E54C/D58C mutant channel by MMTS could be
      reversed by the reducing agent dithiothreitol (200 microm) or by elevating the
      bath ATP concentration above that required to activate maximally the wild type
      channel (>1 mm). Interestingly, the three MTS reagents had qualitatively
      different effects on the duration of channel openings (i.e. channel closing
      rate), namely the duration of openings was negligibly changed by the neutral
      MMTS, decreased by the positively charged MTSET, and increased by the negatively
      charged MTSCE. Our results indicate that the CFTR amino tail modulates both the
      rates of channel opening and channel closing and that the negative charges at
      residues 54 and 58 are important for controlling the duration of channel
      openings.

PMID- 11468286
TI  - Specific interactions between F1 adhesin of Streptococcus pyogenes and N-terminal
      modules of fibronectin.
AB  - Protein F1 is a surface protein of Streptococcus pyogenes that mediates high
      affinity binding to fibronectin (Fn) and facilitates S. pyogenes adherence and
      penetration into cells. The smallest portion of F1 known to retain the full
      binding potential of the intact protein is a stretch of 49 amino acids known as
      the functional upstream domain (FUD). Synthetic and recombinant versions of FUD
      were labeled with fluorescein isothiocyanate and used in fluorescence anisotropy
      experiments. These probes bound to Fn or the 70-kDa fragment of Fn with
      dissociation constants of 8-30 nm. Removal of the N-terminal seven residues of
      FUD did not cause a change in binding affinity. Further N- or C-terminal
      truncations resulted in complete loss of binding activity. Analysis of
      recombinant versions of the 70-kDa fragment that lacked one or several type I
      modules indicates that residues 1-7 of the 49-mer bind to type I modules I1 and
      I2 of the 27-kDa subfragment and the C-terminal residues bind to modules I4 and
      I5. Fluorescein isothiocyanate-labeled 49-mer also bound with lower affinity to
      large Fn fragments that lack the five type I modules of the 27-kDa fragment but
      contain the other seven type 1 modules of Fn. These results indicate that,
      although FUD has a general affinity for type I modules, high affinity binding of
      FUD to Fn is mediated by specific interactions with N-terminal type I modules.

PMID- 11468287
TI  - Dual role of Fyn in the regulation of FAK+6,7 by cannabinoids in hippocampus.
AB  - In hippocampus endocannabinoids modulate synaptic function and plasticity and
      increase tyrosine phosphorylation of several proteins, including focal adhesion
      kinase (FAK). Autophosphorylation of FAK on Tyr-397 is generally a critical step
      for its activation, allowing the recruitment of Src family kinases, and
      phosphorylation of FAK and associated proteins. We have examined the mechanisms
      of the regulation of FAK by cannabinoids in rat and mouse hippocampal slices.
      Anandamide and 2-arachidonoylglycerol, two endocannabinoids, and Delta9
      tetrahydrocannabinol, stimulated tyrosine phosphorylation of FAK+6,7, a neuronal
      splice isoform of FAK, on several residues including Tyr-397. Cannabinoids
      increased phosphorylation of p130-Cas, a protein associated with FAK, but had no
      effect on PYK2, a tyrosine kinase related to FAK and enriched in hippocampus.
      Pharmacological experiments and the use of knockout mice demonstrated that the
      effects of cannabinoids were mediated through CB1 receptors. These effects were
      sensitive to manipulation of cAMP-dependent protein kinase, suggesting that they
      were mediated by inhibition of a cAMP pathway. PP2, an Src family kinase
      inhibitor, prevented the effects of cannabinoids on p130-Cas and on FAK+6,7
      tyrosines 577 and 925, but not 397, indicating that FAK autophosphorylation was
      upstream of Src family kinases in response to CB1-R stimulation. Endocannabinoids
      increased the association of Fyn, but not Src, with FAK+6,7. In hippocampal
      slices from Fyn -/- mice, the levels of p130-Cas were increased, and the effects
      of endocannabinoids on tyrosine phosphorylation, including of Tyr-397, were
      completely abolished. These results demonstrate the specific functional
      association of Fyn with FAK+6,7 in a pathway regulated by endocannabinoids, in
      which Fyn may play roles dependent and independent of its catalytic activity.

PMID- 11468288
TI  - Investigation of the catalytic site within the ATP-grasp domain of Clostridium
      symbiosum pyruvate phosphate dikinase.
AB  - Pyruvate phosphate dikinase (PPDK) catalyzes the interconversion of ATP, P(i),
      and pyruvate with AMP, PP(i), and phosphoenolpyruvate (PEP) in three partial
      reactions as follows: 1) E-His + ATP --> E-His-PP.AMP; 2) E-His-PP.AMP + P(i) -->
      E-His-P.AMP.PP(i); and 3) E-His-P + pyruvate --> E.PEP using His-455 as the
      carrier of the transferred phosphoryl groups. The crystal structure of the
      Clostridium symbiosum PPDK (in the unbound state) reveals a three-domain
      structure consisting of consecutive N-terminal, central His-455, and C-terminal
      domains. The N-terminal and central His-455 domains catalyze partial reactions 1
      and 2, whereas the C-terminal and central His-455 domains catalyze partial
      reaction 3. Attempts to obtain a crystal structure of the enzyme with substrate
      ligands bound at the nucleotide binding domain have been unsuccessful. The object
      of the present study is to demonstrate Mg(II) activation of catalysis at the
      ATP/P(i) active site, to identify the residues at the ATP/P(i) active site that
      contribute to catalysis, and to identify roles for these residues based on their
      positions within the active site scaffold. First, Mg(II) activation studies of
      catalysis of E + ATP + P(i) --> E-P + AMP + PP(i) partial reaction were carried
      out using a truncation mutant (Tem533) in which the C-terminal domain is absent.
      The kinetics show that a minimum of 2 Mg(II) per active site is required for the
      reaction. The active site residues used for substrate/cofactor binding/activation
      were identified by site-directed mutagenesis. Lys-22, Arg-92, Asp-321, Glu-323,
      and Gln-335 mutants were found to be inactive; Arg-337, Glu-279, Asp-280, and Arg
      135 mutants were partially active; and Thr-253 and Gln-240 mutants were almost
      fully active. The participation of the nucleotide ribose 2'-OH and alpha-P in
      enzyme binding is indicated by the loss of productive binding seen with substrate
      analogs modified at these positions. The ATP, P(i), and Mg(II) ions were docked
      into the PPDK N-terminal domain crevice, in an orientation consistent with
      substrate/cofactor binding modes observed for other members of the ATP-Grasp fold
      enzyme superfamily and consistent with the structure-function data. On the basis
      of this docking model, the ATP polyphosphate moiety is oriented/activated for
      pyrophosphoryl transfer through interaction with Lys-22 (gamma-P), Arg-92 (alpha
      P), and the Gly-101 to Met-103 loop (gamma-P) as well as with the Mg(II)
      cofactors. The P(i) is oriented/activated for partial reaction 2 through
      interaction with Arg-337 and a Mg(II) cofactor. The Mg(II) ions are bound through
      interaction with Asp-321, Glu-323, and Gln-335 and substrate. Residues Glu-279,
      Asp-280, and Arg-135 are suggested to function in the closure of an active site
      loop, over the nucleotide ribose-binding site.

PMID- 11468289
TI  - Phytosphingosine as a specific inhibitor of growth and nutrient import in
      Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, we have demonstrated a necessary role for
      sphingolipids in the heat stress response through inhibition of nutrient import
      (Chung, N., Jenkins, G. M., Hannun, Y. A., Heitman, J., and Obeid, L. M. (2000)
      J. Biol. Chem. 275, 17229-17232). In this study, we used a combination of
      pharmacological and genetic approaches to determine which endogenous sphingolipid
      is the likely mediator of growth inhibition. When cells were treated with
      exogenous phytosphingosine (PHS, 20 microm) or structurally similar or
      metabolically related molecules, including 3-ketodihydrosphingosine,
      dihydrosphingosine, C(2)-phytoceramide (PHC), and stearylamine, only PHS
      inhibited growth. Also, PHS was shown to inhibit uptake of uracil, tryptophan,
      leucine, and histidine. Again this effect was specific to PHS. Because of the
      dynamic nature of sphingolipid metabolism, however, it was difficult to conclude
      that growth inhibition was caused by PHS itself. By using mutant yeast strains
      defective in various steps in sphingolipid metabolism, we further determined the
      specificity of PHS. The elo2Delta strain, which is defective in the conversion of
      PHS to PHC, was shown to have slower biosynthesis of ceramides and to be
      hypersensitive to PHS (5 microm), suggesting that PHS does not need to be
      converted to PHC. The lcb4Delta lcb5Delta strain is defective in the conversion
      of PHS to PHS 1-phosphate, and it was as sensitive to PHS as the wild-type
      strain. The syr2Delta mutant strain was defective in the conversion of DHS to
      PHS. Interestingly, this strain was resistant to high concentrations of DHS (40
      microm) that inhibited the growth of an isogenic wild-type strain, demonstrating
      that DHS needs to be converted to PHS to inhibit growth. Together, these data
      demonstrate that the active sphingolipid species that inhibits yeast growth is
      PHS or a closely related and yet unidentified metabolite.

PMID- 11468290
TI  - Involvement of phospholipase D in sphingosine 1-phosphate-induced activation of
      phosphatidylinositol 3-kinase and Akt in Chinese hamster ovary cells
      overexpressing EDG3.
AB  - Phospholipase D (PLD), phosphatidylinositol 3-kinase (PI3K), and Akt are known to
      be involved in cellular signaling related to proliferation and cell survival. In
      this report, we provide evidence that PLD links sphingosine 1-phosphate (S1P)
      induced activation of the G protein-coupled EDG3 receptor to stimulation of PI3K
      and its downstream effector Akt in Chinese hamster ovary (CHO) cells. S1P
      stimulation of EDG3-overexpressing CHO cells but not vector-transfected cells
      induced activation of PLD, PI3K, and Akt in a time- and dose-dependent manner.
      Akt phosphorylation was prevented by the PI3K inhibitors wortmannin and LY294002
      (2-(4-monrpholinyl)-8-phenyl-4H-1-benzopyran-4-one), indicating that Akt
      activation was dependent on PI3K. S1P-induced activation of PI3K and Akt was
      abrogated by 1-butanol, which inhibited S1P-induced accumulation of phosphatidic
      acid by serving as a phosphatidyl group acceptor in the transphosphatidylation
      reaction catalyzed by PLD, whereas both PI3K and Akt activation were not
      inhibited by 2-butanol without such reaction. Co-expression of wild-type PLD2
      with myc-Akt resulted in increased Akt activation in response to S1P. In
      contrast, co-expression of a catalytically inactive mutant of PLD2 eliminated the
      S1P-induced Akt activation. The treatment of EDG3-expressing CHO cells with
      exogenous Streptomyces chromofuscus PLD, which caused an accumulation of
      phosphatidic acid, resulted in increases in PI3K activity and the phosphorylation
      of Akt, the latter of which was completely abolished by LY294002. Furthermore,
      S1P-induced membrane ruffling, which was dependent on PI3K and Rac, was inhibited
      by 1-butanol, but not by 2-butanol. These results demonstrate that PLD
      participates in the activation of PI3K and Akt stimulation of EDG3 receptor.

PMID- 11468291
TI  - A novel mechanism of nuclear photosynthesis gene regulation by redox signals from
      the chloroplast during photosystem stoichiometry adjustment.
AB  - Photosynthetic organisms acclimate to long term changes in the environmental
      light quality by an adjustment of their photosystem stoichiometry to maintain
      photosynthetic efficiency. By using light sources that predominantly excite
      either photosystem I (PSI) or photosystem II (PSII), we studied the effects of
      excitation imbalances between both photosystems on nuclear PSI gene transcription
      in transgenic tobacco seedlings with promoter::beta-glucuronidase gene fusions.
      Shifts from PSI to PSII light sources (and vice versa) induced changes in the
      reduction/oxidation state of intersystem redox components, and acclimation of
      tobacco seedlings to such changes were monitored by changes in chlorophyll a/b
      ratios and in vivo chlorophyll a fluorescence. The ferredoxin-NADP(+)
      oxidoreductase gene promoter did not respond to these treatments, those from the
      genes for subunits PsaD and PsaF of PSI are activated by a reduction signal, and
      the plastocyanin promoter responded to both reduction and oxidation signals.
      Additional experiments with photosynthetic electron transport inhibitors 3-(3',4'
      dichlorophenyl)-1,1'-dimethyl urea and 2,5-dibromo-3-methyl-6-isopropyl-p
      benzoquinone demonstrated that the redox state of the plastoquinone pool controls
      the activity of the plastocyanin promoter, whereas subunit PsaD and PsaF gene
      transcription is regulated by other photosynthesis-derived signals. Thus, the
      expression of nuclear-encoded PSI genes is controlled by diverse light quality
      dependent redox signals from the plastids during photosystem stoichiometry
      adjustment.

PMID- 11468292
TI  - The Rac GTPase-activating protein RotundRacGAP interferes with Drac1 and Dcdc42
      signalling in Drosophila melanogaster.
AB  - RhoGTPases are negatively regulated by GTPase-activating proteins (GAPs). Here we
      demonstrate that Drosophila RotundRacGAP is active in vitro on Drac1 and Dcdc42
      but not Drho1. Similarly, in yeast, RotundRacGAP interacts specifically with
      Drac1 and Dcdc42, as well as with their activated V12 forms, showing a
      particularly strong interaction with Dcdc42V12. In the fly, lowering RotundRacGAP
      dosage specifically modifies eye defects induced by expressing Drac1 or Dcdc42
      but not Drho1, confirming that Drac1 and Dcdc42 are indeed in vivo targets of
      RotundRacGAP. Furthermore, embryonic-directed expression of either RotundRacGAP,
      or dominant negative Drac1N17, transgenes induces similar defects in dorsal
      closure and inhibits Drac1-dependent cytoskeleton assembly at the leading edge.
      Expression of truncated forms of RotundRacGAP shows that the GAP domain of
      RotundRacGAP is essential for its function. Unexpectedly, transgenes encoding
      Drac1N17, Dcdc42N17, or RotundRacGAP do not affect the c-Jun N-terminal kinase
      dependent gene expression of decapentaplegic and puckered, indicating that
      another Drac1-independent signal redundantly activates this pathway. Finally, in
      a situation where Drac1 is constitutively activated, RotundRacGAP greatly reduces
      the ectopic expression of decapentaplegic, possibly by negatively regulating
      Dcdc42.

PMID- 11468293
TI  - Different cleavage specificities of the dual catalytic domains in chitinase from
      the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1.
AB  - The chitinase from the hyperthermophilic archaeon Thermococcus kodakaraensis
      KOD1, Tk-ChiA, has an interesting multidomain structure containing dual catalytic
      domains and triple chitin-binding domains. To determine the biochemical
      properties of each domain, we constructed deletion mutant genes corresponding to
      the individual catalytic domains and purified the recombinant proteins. A
      synergistic effect was observed when chitin was degraded in the presence of both
      catalytic domains, suggesting different cleavage specificity of these domains.
      Analyses of degradation products from N-acetyl-chitooligosaccharides and their
      chromogenic derivatives with thin layer chromatography indicated that the N
      terminal catalytic domain mainly hydrolyzed the second glycosidic bond from the
      nonreducing end of the oligomers, whereas the C-terminal domain randomly
      hydrolyzed glycosidic bonds other than the first bond from the nonreducing end.
      Both catalytic domains formed diacetyl-chitobiose as a major end product and
      possessed transglycosylation activity. Further analysis of degradation products
      from colloidal chitin with high performance liquid chromatography showed that the
      N-terminal catalytic domain exclusively liberated diacetyl-chitobiose, whereas
      reactions with the C-terminal domain led to N-acetyl-chitooligosaccharides of
      various lengths. These results demonstrated that the N-terminal and C-terminal
      catalytic domains functioned as exo- and endochitinases, respectively. The
      biochemical results provide a physiological explanation for the presence of two
      catalytic domains with different specificity and suggest a cooperative function
      between the two on a single polypeptide in the degradation of chitin.

PMID- 11468294
TI  - Mapping of a region within the N terminus of Jak1 involved in cytokine receptor
      interaction.
AB  - Janus kinase 1 (Jak1) is a cytoplasmic tyrosine kinase that noncovalently
      associates with a variety of cytokine receptors. Here we show that the in vitro
      translated N-terminal domains of Jak1 are sufficient for binding to a
      biotinylated peptide comprising the membrane-proximal 73 amino acids of gp130,
      the signal-transducing receptor chain of interleukin-6-type cytokines. By the
      fold recognition approach amino acid residues 36-112 of Jak1 were predicted to
      adopt a beta-grasp fold, and a structural model was built using ubiquitin as a
      template. Substitution of Tyr(107) to alanine, a residue conserved among Jaks and
      involved in hydrophobic core interactions of the proposed beta-grasp domain,
      abrogated binding of full-length Jak1 to gp130 in COS-7 transfectants. By further
      mutagenesis we identified the loop 4 region of the Jak1 beta-grasp domain as
      essential for gp130 association and gp130-mediated signal transduction. In Jak1
      deficient U4C cells reconstituted with the loop 4 Jak1 mutants L80A/Y81A and
      Delta(Tyr(81)-Ser(84)), the interferon-gamma, interferon-alpha, and interleukin-6
      responses were similarly impaired. Thus, loop 4 of the beta-grasp domain plays a
      role in the association of Jak1 with both class I and II cytokine receptors.
      Taken together the structural model and the mutagenesis data provide further
      insight into the interaction of Janus kinases with cytokine receptors.

PMID- 11468295
TI  - Ezrin interacts with focal adhesion kinase and induces its activation
      independently of cell-matrix adhesion.
AB  - Ezrin, a membrane-cytoskeleton linker, is required for cell morphogenesis,
      motility, and survival through molecular mechanisms that remain to be elucidated.
      Using the N-terminal domain of ezrin as a bait, we found that p125 focal adhesion
      kinase (FAK) interacts with ezrin. We show that the two proteins
      coimmunoprecipitate from cultured cell lysates. However, FAK does not interact
      with full-length ezrin in vitro, indicating that the FAK binding site on ezrin is
      cryptic. Mapping experiments showed that the entire N-terminal domain of FAK
      (amino acids 1-376) is required for optimal ezrin binding. While investigating
      the role of the ezrin-FAK interaction, we observed that, in suspended kidney
      derived epithelial LLC-PK1 cells, overproduction of ezrin promoted
      phosphorylation of FAK Tyr-397, the major autophosphorylation site, creating a
      docking site for FAK signaling partners. Treatment of the cells with a Src family
      kinase inhibitor reduced the phosphorylation of Tyr-577 but not that of Tyr-397,
      indicating that ezrin-mediated FAK activation does not require the activity of
      Src kinases. Altogether, these observations indicate that ezrin is able to
      trigger FAK activation in signaling events that are not elicited by cell-matrix
      adhesion.

PMID- 11468296
TI  - More evidence for seizure-induced neuron loss: is hippocampal sclerosis both
      cause and effect of epilepsy?

PMID- 11468297
TI  - Do stutterers have different brains?

PMID- 11468298
TI  - Semantic dementia versus Alzheimer's disease: A matter of semantics?

PMID- 11468299
TI  - Recertification for neurologists.

PMID- 11468300
TI  - Volumetric MRI, pathological, and neuropsychological progression in hippocampal
      sclerosis.
AB  - OBJECTIVE: To examine the relationships between age at onset and duration of
      seizure disorder with severity of hippocampal sclerosis (HS) and cognitive
      functioning in patients with HS and unilateral temporal lobe epilepsy. METHODS:
      Twenty-six subjects had left temporal lobe seizure onset; 20 had right temporal
      onset. Measures were age at seizure onset, duration of seizure disorder divided
      by age (seizure duration), history of febrile convulsion (FC), ratio of the
      smaller hippocampal volume to the larger (HF) as determined by volumetric MRI,
      and pathologic HS grade. RESULTS: Results showed that pathologic HS grade and HF
      were positively related to seizure duration, and negatively related to seizure
      onset. When subjects were divided into onset prior to age 10 versus later,
      subjects with earlier onset had higher mean pathologic HS grade and smaller (more
      asymmetric) mean HF. When subjects were divided into seizure duration <0.5 (i.e.,
      less than half current lifetime) vs greater, subjects with seizure duration > or
      =0.5 had higher mean pathologic HS grade and lower mean HF. There was also
      evidence for earlier age at seizure onset and longer seizure duration being
      associated with worse performance on neuropsychological measures. FC was not
      related to either seizure duration or age at seizure onset, but patients with a
      history of FC showed higher pathologic HS grade and lower HF. A history of FC was
      not related to cognitive functioning. CONCLUSIONS: Unilateral HS patients with
      earlier seizure onset and longer duration of epilepsy have more severe HS and
      greater hippocampal volume asymmetry. This suggests that HS may be a progressive
      disorder with risk for cognitive dysfunction.

PMID- 11468301
TI  - Sturge-Weber syndrome: correlation between clinical course and FDG PET findings.
AB  - OBJECTIVE: To determine whether the extent and degree of glucose hypometabolism
      defined by PET correlate with seizure characteristics, cognitive function, and
      interictal EEG abnormalities in children with unilateral cerebral involvement of
      Sturge-Weber syndrome (SWS). METHODS: 2-Deoxy-2[18F]fluoro-D-glucose (FDG) PET
      was performed in 13 children (age range 0.7 to 15.1 years; five boys, eight
      girls) with unilateral SWS. Based on asymmetries between homologous cortical
      areas in FDG PET images, cortical areas of mildly (10% to 20% decrease), and
      severely (>20% decrease) asymmetric cortical metabolism were defined. These areas
      were normalized to the size of the ipsilateral hemisphere and correlated with
      clinical seizure characteristics, full-scale IQ, and interictal EEG
      abnormalities. RESULTS: Both seizure frequency (p = 0.027) and lifetime number of
      seizures (p = 0.017) showed a positive correlation with the area (expressed as
      the percentage of cortical area of ipsilateral hemisphere) of mildly asymmetric
      cortical metabolism. Patients with higher IQ had a shorter duration of epilepsy
      (p = 0.044) and a larger area of severely asymmetric cortical metabolism (p =
      0.044). Patients with bilateral interictal EEG abnormalities had larger lifetime
      number of seizures (p = 0.042), lower IQ (p = 0.024), and smaller area of
      severely asymmetric cortical metabolism (p = 0.019) than those with only
      ipsilateral EEG abnormalities. CONCLUSIONS: Association of severely asymmetric
      cortical metabolism with relatively preserved cognitive function in SWS suggests
      that functional reorganization occurs more readily when cortex is severely rather
      than mildly damaged. Therefore, the area of mildly asymmetric cortical metabolism
      may exert a nociferous effect on the remaining of the brain. Thus, the extent and
      degree of glucose asymmetry detected by PET are sensitive markers of seizure
      severity and cognitive decline in SWS.

PMID- 11468302
TI  - Visual field constriction: accumulation of vigabatrin but not tiagabine in the
      retina.
AB  - BACKGROUND: The antiepileptic drug (AED) vigabatrin (VGB) causes concentric
      visual field constriction. Anecdotal reports involving tiagabine (TGB) have
      implied that this may be a class effect of all AEDs with gamma-aminobutyric acid
      (GABA)-related actions. We investigated the pharmacokinetic and pharmacodynamic
      profiles of VGB and TGB in rat brain and eye. METHODS: Adult male rats (n = 8)
      were administered 0.9% saline (control), VGB (500 or 1,000 mg/kg), or TGB (5, 10,
      or 20 mg/kg). At 1 (TGB) and 4 hours (VGB) postdosing, the animals were killed, a
      blood sample was obtained, their brains were dissected into five anatomic
      regions, and the retina and vitreous humor were isolated from each eye. Samples
      were analyzed for GABA concentrations and the activity of the enzyme GABA
      transaminase (GABA-T). Plasma and tissue drug concentrations were also
      determined. RESULTS: VGB treatment produced a decrease in the activity of GABA-T
      and a rise in GABA concentrations in all tissues investigated. This effect was
      most pronounced in the retina. VGB concentrations were as much as fivefold higher
      in the retina than in the brain. TGB was without effect on GABA concentrations
      and activity of GABA-T. TGB concentrations were notably lower in the retina than
      in the brain. CONCLUSIONS: Accumulation of VGB in the retina, with or without an
      increase in GABA, may be responsible for the visual field constriction reported
      clinically. In contrast, TGB had no effect on GABA concentrations and did not
      accumulate in the retina. These results suggest that TGB is unlikely to cause
      visual field defects in humans.

PMID- 11468303
TI  - Prevalence and predictors of early seizure and status epilepticus after first
      stroke.
AB  - BACKGROUND: Early seizure (ES) has been reported in 2% to 6% of strokes and is a
      predictor of recurrent seizures. Acute stroke has been reported to cause 22% of
      all cases of status epilepticus in adults. The determinants of ES and status
      epilepticus (SE) after stroke, however, are not well understood. METHODS: An
      incidence study was conducted to identify all cases of first stroke in adult
      residents of northern Manhattan. Cases of ES and SE within 7 days of stroke were
      identified through medical record review. Statistical analyses were performed
      using univariate and multivariate logistic regression models. RESULTS: The cohort
      consisted of 904 patients; ES occurred in 37 (4.1%). The frequency of ES by
      stroke subtype and location was deep infarct 0.6% (2/356), lobar infarct 5.9%
      (20/341), deep intracerebral hemorrhage (ICH) 4.0% (4/101), lobar ICH 14.3%
      (7/49), and subarachnoid hemorrhage 8.0% (4/50). SE occurred in 10 patients
      (1.1%), representing 27.0% of patients with ES. Diabetes, hypertension, current
      smoking, alcohol use, age, gender, and race/ethnicity were not significant
      determinants of ES. In a subgroup of patients who had an NIH stroke scale (NIHSS)
      score recorded, NIHSS score was not an independent predictor of ES in
      multivariate analysis. After accounting for stroke severity, ES was not a
      predictor of 30-day case fatality. CONCLUSIONS: Lesion location and stroke
      subtype are strong determinants of ES risk, even after adjusting for stroke
      severity. ES does not predict 30-day mortality. SE occurs in more than one
      quarter of patients with ES.

PMID- 11468304
TI  - Anomalous anatomy of speech-language areas in adults with persistent
      developmental stuttering.
AB  - OBJECTIVE: The major aim of this study was to determine whether adults with
      persistent developmental stuttering (PDS) have anomalous anatomy in cortical
      speech-language areas. The major postulate was that anomalous cerebral dominance,
      reflected by anomalous cortical anatomy in various regions, may put an individual
      at increased risk for the development of stuttering. METHODS: Adults with PDS (n
      = 16) and controls (n = 16) matched for age, sex, hand preference, and education
      were studied. Volumetric MRI scans were completed. Frontal (pars triangularis,
      pars opercularis) and temporo-parietal areas (planum temporale, posterior
      ascending ramus) were measured in the left and right hemispheres and
      interhemispheric asymmetries were computed. Gyral variants were assessed within
      these perisylvian cortical speech-language areas. RESULTS: The right and left
      planum temporale were significantly larger in the adults with PDS (p = 0.045),
      and the magnitude of the planar asymmetry was reduced (p = 0.003). Some gyral
      variants were unique to the adults with PDS, including a second diagonal sulcus
      and extra gyri along the superior bank of the sylvian fossa. In addition,
      anatomic subgroups emerged based on sex and hand preference. Overall, the adults
      with PDS had significantly more gyral variants (mean = 4.19) than controls (mean
      = 1.31, p < 0.0005). CONCLUSIONS: These results provide strong evidence that
      adults with PDS have anomalous anatomy in perisylvian speech and language areas.
      No one anatomic feature distinguished the groups, but multiple loci within a
      widely distributed neural network differed between groups. These results provide
      the first evidence that anatomic anomalies within perisylvian speech-language
      areas may put an individual at risk for the development of stuttering.

PMID- 11468305
TI  - Differing patterns of temporal atrophy in Alzheimer's disease and semantic
      dementia.
AB  - OBJECTIVE: To characterize and quantify the patterns of temporal lobe atrophy in
      AD vs semantic dementia and to relate the findings to the cognitive profiles.
      Medial temporal lobe atrophy is well described in AD. In temporal variant
      frontotemporal dementia (semantic dementia), clinical studies suggest polar and
      inferolateral temporal atrophy with hippocampal sparing, but quantification is
      largely lacking. METHODS: A volumetric method for quantifying multiple temporal
      structures was applied to 26 patients with probable AD, 18 patients with semantic
      dementia, and 21 matched control subjects. RESULTS: The authors confirmed the
      expected bilateral hippocampal atrophy in AD relative to controls, with
      involvement of the amygdala bilaterally and the right parahippocampal gyrus.
      Contrary to expectations, patients with semantic dementia had asymmetric
      hippocampal atrophy, more extensive than AD on the left. As predicted, the
      semantic dementia group showed more severe involvement of the temporal pole
      bilaterally and the left amygdala, parahippocampal gyrus (including the
      entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri.
      Performance on semantic association tasks correlated with the size of the left
      fusiform gyrus, whereas naming appeared to depend upon a wider left temporal
      network. Episodic memory measures, with the exception of recognition memory for
      faces, did not correlate with temporal measures. CONCLUSIONS: Hippocampal atrophy
      is not specific for AD but is also seen in semantic dementia. Distinguishing the
      patients with semantic dementia was the severe global but asymmetric (left >
      right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral
      temporal gyri. These findings have implications for diagnosis and understanding
      of the cognitive deficits in AD and semantic dementia.

PMID- 11468306
TI  - Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a
      population-based study.
AB  - OBJECTIVE: To determine diagnostic accuracy for AD in a population-based study of
      Japanese-American men. AD is neuropathologically confirmed for more than 80% of
      cases at major referral centers (primarily Caucasians); however, information on
      diagnostic accuracy in population-based studies and studies of different ethnic
      groups is limited. METHODS: There were 3,734 men who participated in the Honolulu
      Asia Aging Study 1991 through 1993 dementia examination and 2,603 in the 1994
      through 1996 examination. Diagnoses were based on published criteria.
      Neuropathologists blinded to clinical data quantified neurofibrillary tangles
      (NFT) and neuritic plaques (NP). RESULTS: Of 220 autopsied subjects, clinical
      evaluation revealed 68 with normal cognition, 73 intermediate, and 79 with
      dementia: 20 AD, 27 vascular dementia, 19 AD + other, and 13 other dementia.
      Among 20 cases with pure AD, the median value for maximum neocortical NFT density
      was 6.9/mm(2) and for neocortical NP density was 8.0/mm2. Corresponding densities
      for other groups were <3.0/mm2. Using established neuropathologic criteria, 25%
      (5/20) of clinical AD cases had enough NP to meet definite AD criteria, whereas
      65% (13/20) had sufficient NP to meet neuropathologic definite or probable AD
      criteria. Among nine AD cases with moderately severe dementia, only two (22%) had
      NP densities great enough to meet definite neuropathologic criteria, whereas
      seven (78%) met neuropathologic criteria for probable AD. CONCLUSIONS:
      Neuropathologic confirmation and NP density among decedents with clinical AD in
      this population-based study were lower than reported by referral centers and
      similar to reports from two other community studies. Ethnic differences in
      propensity for amyloid deposition as well as differences in clinical severity and
      representativeness of cases might contribute to these findings.

PMID- 11468307
TI  - Mapping callosal morphology and cognitive correlates: effects of heavy prenatal
      alcohol exposure.
AB  - BACKGROUND: Abnormalities of the corpus callosum (CC) have been documented in
      fetal alcohol syndrome (FAS), ranging from subtle decrements in its size to
      partial and even complete agenesis. Prenatal exposure to alcohol is also known to
      result in neurocognitive deficits. OBJECTIVE: To 1) investigate abnormalities in
      size, shape, and location of the CC within the brain in individuals with FAS and
      in those exposed to high amounts of alcohol prenatally but without FAS (PEA
      group); and 2) determine if there is a relationship between callosal
      dysmorphology and cognitive test performance. METHODS: MRI and novel surface
      based image analytic methods were used. Twenty alcohol-exposed subjects (8 to 22
      years) along with 21 normal controls (8 to 25 years) were studied with high
      resolution MRI and measures of verbal learning and visuospatial abilities.
      RESULTS: In addition to callosal area reductions, most severe in the splenium,
      the CC is significantly displaced in patients exposed to alcohol prenatally. In
      the alcohol-exposed group, this structure lies more anterior and inferior in
      posterior regions with relatively normal localization of anterior regions. These
      findings are significant in the FAS group, and a similar but less severe pattern
      is observed in the PEA patients. The authors show that the amount of CC
      displacement is correlated with impairment in verbal learning ability and that CC
      displacement is a better predictor of verbal learning than regional CC area. The
      brain-behavior relationship is only significant within the alcohol-exposed group,
      and the effect is not solely mediated by overall impaired verbal intellectual
      functioning. CONCLUSIONS: These results further emphasize the vulnerability of
      midline brain structures to prenatal alcohol exposure.

PMID- 11468308
TI  - Unusual brain growth patterns in early life in patients with autistic disorder:
      an MRI study.
AB  - OBJECTIVE: To quantify developmental abnormalities in cerebral and cerebellar
      volume in autism. METHODS: The authors studied 60 autistic and 52 normal boys
      (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned
      when 5 years or older. The other 30 were scanned when 2 through 4 years of age
      and then diagnosed with autism at least 2.5 years later, at an age when the
      diagnosis of autism is more reliable. RESULTS: Neonatal head circumferences from
      clinical records were available for 14 of 15 autistic 2- to 5-year-olds and, on
      average, were normal (35.1 +/- 1.3 cm versus clinical norms: 34.6 +/- 1.6 cm),
      indicative of normal overall brain volume at birth; one measure was above the
      95th percentile. By ages 2 to 4 years, 90% of autistic boys had a brain volume
      larger than normal average, and 37% met criteria for developmental macrencephaly.
      Autistic 2- to 3-year-olds had more cerebral (18%) and cerebellar (39%) white
      matter, and more cerebral cortical gray matter (12%) than normal, whereas older
      autistic children and adolescents did not have such enlarged gray and white
      matter volumes. In the cerebellum, autistic boys had less gray matter, smaller
      ratio of gray to white matter, and smaller vermis lobules VI-VII than normal
      controls. CONCLUSIONS: Abnormal regulation of brain growth in autism results in
      early overgrowth followed by abnormally slowed growth. Hyperplasia was present in
      cerebral gray matter and cerebral and cerebellar white matter in early life in
      patients with autism.

PMID- 11468309
TI  - Brain proton magnetic resonance spectroscopy in children exposed to
      methamphetamine in utero.
AB  - OBJECTIVE: To examine the possible neurotoxic effects of prenatal methamphetamine
      exposure on the developing brain using 1H-MRS. METHODS: Methamphetamine-exposed
      children (n = 12) and age-matched unexposed control subjects (n = 14) were
      evaluated with MRI, localized 1H-MRS, and a Child Behavior Checklist. Metabolite
      concentrations of N-acetyl-containing compounds (NA), total creatine (Cr),
      choline-containing compounds, myoinositol, and glutamate + glutamine were
      measured in the frontal white matter and striatum. RESULTS: Despite an absence of
      visible structural abnormalities in either group, children exposed to
      methamphetamine in utero had higher [Cr] (+10%, p = 0.02) in the striatum. [NA],
      primarily a measure of N-acetylaspartate, was normal in both regions, which
      suggests no significant neuronal loss or damage in the two brain regions
      examined. There were no differences in reported behavior problems among the
      methamphetamine-exposed children relative to the unexposed group. CONCLUSIONS:
      The authors found increased [Cr] in the striatum with relatively normal [NA] in
      children exposed to methamphetamine. These findings suggest an abnormality in
      energy metabolism in the brains of children exposed to methamphetamine in utero.

PMID- 11468310
TI  - Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD.
AB  - OBJECTIVE: To determine whether hippocampal neurons and choroidal epithelial
      cells demonstrate a mitochondrial enzyme deficiency in AD more frequently than in
      normal aging. BACKGROUND: High levels of mutant mitochondrial DNA (mtDNA) cause a
      deficiency in cytochrome c oxidase (COX) (complex IV activity) because three of
      its 13 subunits are encoded for by mtDNA. In contrast, succinate dehydrogenase
      (SDH) (complex II activity) remains intact because all of its subunits are
      nuclear encoded. The histologic hallmark of cells containing high levels of mtDNA
      mutation in both primary mtDNA disorders and normal aging muscle is the presence
      of COX-deficient SDH-positive cells. METHODS: The authors applied a sequential
      histochemical method for COX and SDH to hippocampal sections in 17 AD and 17 age
      matched control brains. This confers the advantages of both looking at individual
      cells in situ and measuring the actual mitochondrial complex activity rather than
      simply the complex quantity. RESULTS: COX-deficient SDH-positive hippocampal
      neurons and choroidal epithelial cells are more prevalent in patients with AD
      than in controls. In addition the COX-deficient SDH-positive choroidal cells are
      associated with an enlargement in size. CONCLUSION: This increase in number of
      COX-deficient SDH-positive hippocampal pyramidal neurons and choroid epithelial
      cells provides strong evidence that a substantial mitochondrial enzyme activity
      defect occurs in individual cells more frequently in AD than in normal aging and
      that mitochondria may play a significant role in the pathogenesis of AD.

PMID- 11468311
TI  - Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to
      chromosome 3q27.
AB  - OBJECTIVE: To describe clinical and neuropathologic studies and linkage analysis
      on two sisters with a severe form of leukodystrophy. METHODS: A detailed study
      was performed on the second sister. Genotyping markers for chromosome 3,
      including eight additional markers surrounding the vanishing white matter (VWM)
      locus, were used. RESULTS: During the first year of life, two sisters developed a
      severe neurologic condition after an intercurrent infection. It was accompanied
      by irritability and stupor with rapid loss of their motor abilities. Results of
      extensive metabolic studies were negative. Brain MRI showed severe and diffuse
      abnormalities of the encephalic white matter. Neuropathologic examination showed
      a severe lack of myelin with diffuse vacuolating white matter lesions in the
      brain, associated with an increased density of oligodendrocytes and a reduced
      number of astrocytes on morphometric analysis. In sharp contrast, the spinal cord
      white matter was preserved. The affected sibpairs shared a common haplotype for a
      broad region in chromosome 3. They were homozygous between markers D3S1565 and
      D3S3669, including the VWM locus. CONCLUSIONS: This condition is an unusual
      variant of childhood ataxia with diffuse central hypomyelination (CACH)/VWM, with
      characteristic shrinking and perivascular clustering of astrocytes. Haplotype
      analysis suggests that this variant is allelic to the VWM locus located on
      chromosome 3q27.

PMID- 11468312
TI  - Genomic organization of the dysferlin gene and novel mutations in Miyoshi
      myopathy.
AB  - OBJECTIVE: Mutations in the skeletal muscle gene dysferlin cause two autosomal
      recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle
      muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the
      genomic organization of the dysferlin gene and conduct mutational screening and a
      survey of clinical features in 21 patients with defined molecular defects in the
      dysferlin gene. METHODS: Genomic organization of the gene was determined by
      comparing the dysferlin cDNA and genomic sequence in P1-derived artificial
      chromosomes (PACs) containing the gene. Mutational screening entailed
      conformational analysis and sequencing of genomic DNA and cDNA. Clinical records
      of patients with defined dysferlin gene defects were reviewed retrospectively.
      RESULTS: The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic
      DNA. Mutational screening revealed nine novel mutations associated with MM. The
      range of onset in this patient group was narrow with a mean of 19.0 +/- 3.9
      years. CONCLUSION: This study confirms that the dysferlin gene is mutated in MM
      and LGMD2B and extends understanding of the timing of onset of the disease.
      Knowledge of the genomic organization of the gene will facilitate mutation
      detection and investigations of the molecular biologic properties of the
      dysferlin gene.

PMID- 11468313
TI  - Presynaptic congenital myasthenic syndrome due to quantal release deficiency.
AB  - OBJECTIVE: To provide clinical, electrophysiologic, and ultrastructural findings
      in three patients with a presynaptic congenital myasthenic syndrome (CMS).
      BACKGROUND: Familial infantile myasthenia and paucity of synaptic vesicles are
      the only two fully characterized CMS. We are describing here three patients with
      another form of presynaptic CMS characterized by deficiency of the action
      potential-dependent release without reduction of the spontaneous release of
      neurotransmitter from the nerve terminal. METHODS: The authors performed
      electromyography and anconeus muscle biopsies that included intracellular
      recordings and electron microscopy of the neuromuscular junction in three
      patients with presynaptic CMS. They also sequenced part of the P/Q-calcium
      alpha(1)-subunit gene (CACNA1A) and the acetylcholine receptor subunit (AChR)
      genes in these patients. RESULTS: In these patients there were additional
      neurologic findings including nystagmus and ataxia. In all three patients the end
      plate potential quantal content (m) was markedly reduced but neither the
      amplitudes nor the frequencies of miniature end-plate potentials were diminished.
      Ultrastructurally, postsynaptic end-plate folds, nerve terminal size, and
      synaptic vesicle number were normal but double-membrane-bound sacs containing
      synaptic vesicles were present in the nerve terminal of all three patients. The
      screening of reported pathogenic mutations in the CACNA1A and a mutational
      analysis of AChR subunit genes were negative. CONCLUSION: This form of CMS
      appears to result only from a deficiency of the quantal release of
      neurotransmitter that may be due to an abnormal calcium mechanism or impaired
      endocytosis and recycling of synaptic vesicles.

PMID- 11468314
TI  - Patterns of disease in concordant parent-child pairs with multiple sclerosis.
AB  - BACKGROUND: Although the exact etiology of MS remains elusive, there is good
      evidence that genetic factors play an important role. These factors are likely to
      be polygenic, exerting both independent and interactive effects on the expression
      of MS. They may determine susceptibility and/or shape the clinical course.
      METHODS: The authors studied clinical phenotype in 245 concordant parent-child
      pairs recruited from a national register of familial disease over a 10-year
      period. Data were examined in order to determine the effect of parental sex on
      expression of disease in the offspring. RESULTS: Allowing for the observed sex
      ratio of 2.6 F:1 M in this group of patients, sex pairings of parents and
      offspring were close to those expected. When assessed independently there was no
      evidence that either the sex of the affected offspring or the line of inheritance
      influenced disability, age at onset, or disease course. However, trends were
      observed toward greater disability and an increased frequency of primary
      progressive disease in offspring of affected fathers and an earlier age at onset
      in offspring of affected mothers. The highest mean Expanded Disability Status
      Scale score was observed in male offspring of affected fathers (5.64) and this
      group was also more likely to have primary progressive disease (OR 1.92). Thirty
      one percent of families had an additionally affected offspring with no
      preferential maternal or paternal transmission. CONCLUSIONS: In offspring of
      concordant parent-child families with MS who are at high risk of inheriting
      increased numbers of susceptibility genes there is no evidence for a parent of
      origin effect distorting sex ratios in affected offspring, but parent of origin
      may influence disability and disease course as well as increasing the risk to
      additional offspring within the same family. The mechanism of these effects is
      not clear but may result from interactions between genes encoded at different
      loci (epistasis), which each independently influence susceptibility and
      phenotype.

PMID- 11468315
TI  - Predictive value of serum interleukin-6 level in influenza virus-associated
      encephalopathy.
AB  - OBJECTIVE: In Japan, >200 children with influenza virus-associated encephalopathy
      were reported in 1999 and the mortality rate was high. The levels of tumor
      necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) in both CSF and serum
      were significantly increased in severe cases. The authors found a correlation
      between elevated serum cytokine levels and mortality and neurologic morbidity.
      METHODS: TNFalpha, IL-6, soluble tumor necrosis factor receptor 1 (sTNF-R1),
      interferon-gamma (IFNgamma), and IL-2 were measured by the ELISA method in sera
      from six children with encephalopathy before and during therapy, and in six age
      matched controls with influenza type A virus infection. RESULTS: The increases in
      the serum TNFalpha, IL-6, and sTNF-R1 levels were statistically significant at
      the onset of symptoms before therapy, but the IL-6 level was most useful for
      diagnosis. The serum IL-6 levels were >6,000 pg/mL in children with brain stem
      dysfunction, about 150 pg/mL in children without brain stem dysfunction, and <80
      pg/mL in controls. The time course of the serum IL-6 level also reflected the
      clinical condition. Once the serum IL-6 level was increased to >15,000 pg/mL,
      none of the children survived. The lower the maximal serum IL-6 level, the milder
      the CNS sequelae. CONCLUSION: The serum IL-6 level may be the most useful
      indicator for the diagnosis and the clinical severity of influenza virus
      associated encephalopathy.

PMID- 11468316
TI  - Motor pattern of periodic limb movements during sleep.
AB  - BACKGROUND: The pathophysiology of periodic limb movements in sleep (PLMS) in
      restless legs syndrome (RLS) is unclear. OBJECTIVE: The authors
      neurophysiologically investigated PLMS in patients with idiopathic RLS in order
      to obtain information on the origin and pathophysiology of the movements.
      METHODS: Ten patients with idiopathic RLS underwent electromyography with nerve
      conduction velocity (EMG-CV), somatosensory evoked potentials (SEPs),
      transcranial magnetic stimulation (TMS), nocturnal videopolysomnography, and
      multiple sleep latency test. The authors analyzed 100 consecutive PLMS for each
      patient to determine how frequently each muscle was involved in the PLMS; how
      frequently EMG activity started in a given muscle; and the time delay and pattern
      of activation between the first and the other activated muscles. RESULTS: EMG-CV,
      SEPs, and TMS findings were all normal; in PLMS, leg muscles were those more
      frequently involved, often with alternation of side. Axial muscles were rarely
      and upper limb muscles sometimes involved. The tibialis anterior was the most
      frequent starting muscle. There was no constant recruitment pattern from one PLMS
      episode to another, even in the same patient. There was no ordinate caudal or
      rostral spread of the EMG activity. CONCLUSION: The recruitment pattern indicates
      the engagement of different, independent, and sometimes unsynchronized generators
      for each PLMS. The authors hypothesize an abnormal hyperexcitability along the
      entire spinal cord, especially its lumbosacral and cervical segments, as the
      primary cause of PLMS, triggered by sleep-related factors located at a
      supraspinal but still unresolved level.

PMID- 11468317
TI  - Inpatient costs, length of stay, and mortality for cerebrovascular events in
      community hospitals.
AB  - BACKGROUND: Accurate estimates of inpatient cost, length of stay (LOS), and
      mortality are necessary for the development of economic models to estimate the
      cost-effectiveness of stroke-related treatments. Estimates based on data from
      academic institutions may not be generalizable to community hospitals. In this
      study, the authors estimated inpatient costs, LOS, and in-hospital mortality for
      patients with subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH),
      ischemic cerebral infarction (ICI), and TIA who were treated in community
      hospitals. METHODS: The authors selected patients using International
      Classification of Diseases-9-Clinical Modification primary diagnosis codes from
      the HBSI EXPLORE database. They analyzed patient-level data and inpatient costs,
      derived from detailed utilization data, for all patients admitted to 137
      community hospitals in 1998. Multivariate statistical techniques were used to
      examine patient-, hospital-, and outcome-related factors associated with
      inpatient costs. RESULTS: Patients with SAH incurred the highest average cost
      ($23,777, n = 1,124), followed by patients with ICH ($10,241, n = 3,139), ICI
      ($5,837, n = 18,740), and TIA ($3,350, n = 7,861). Patient subgroups ranked in
      the same order for average LOS at 11.5 days for SAH, 7.5 days for ICH, 5.9 days
      for ICI, and 3.4 days for TIA. Almost one third of patients with SAH (29.0%) and
      ICH (33.1%) died during hospitalization, whereas 7.0% with ICI and 0.2% with TIA
      died. For each event, as patient age increased, average costs consistently
      decreased. Also, average costs were higher among patients treated in community
      teaching hospitals compared to community nonteaching hospitals for each
      cerebrovascular event (10 to 29%). CONCLUSIONS: Inpatient costs, LOS, and
      mortality for patients with cerebrovascular disease are dependent on patient and
      hospital characteristics.

PMID- 11468318
TI  - Hippocampal sclerosis following brief generalized seizures in adulthood.
AB  - This report describes a patient who had a first generalized tonic clonic seizure
      (GTCS) at the age of 18 years. The initial MRI scan was normal on visual and
      quantitative examination. After a further six GTCS, a second MRI scan showed
      reduced hippocampal volume and increased hippocampal T2 signal, which was
      confirmed in a third scan. Therefore, hippocampal sclerosis may be acquired in
      adulthood after brief GTCS.

PMID- 11468320
TI  - Is carbamazepine teratogenic? A prospective controlled study of 210 pregnancies.
AB  - The Israeli Teratogen Information Service prospectively followed up 210
      pregnancies with first trimester carbamazepine exposure. Pregnancy outcome was
      compared with that of two overlapping controls, matched and general (n = 629),
      exposed to nonteratogenic agents. Our study suggests a twofold increase in the
      rate of major congenital anomalies (12/160 [carbamazepine] versus 18/560 [general
      control]; relative risk 2.24; 95% CI 1.1-4.56) and a birth weight reduction of
      approximately 250 g after in utero exposure to carbamazepine.

PMID- 11468319
TI  - Prolonged febrile convulsions and mesial temporal lobe epilepsy in an identical
      twin.
AB  - The authors report a 30-year-old identical twin who had prolonged febrile
      convulsions (FC) at the age of 8 months, left mesial temporal lobe epilepsy
      beginning at the age of 2 years, and left mesial temporal lobe sclerosis (MTS).
      The unaffected twin had short FC and meningitis at the age of 4 years but
      remained seizure free. Thus, prolonged FC in children younger than 4 years may
      precipitate later development of MTS.

PMID- 11468321
TI  - Labeling of rat neurons by anti-GluR3 IgG from patients with Rasmussen
      encephalitis.
AB  - The authors report the immunocytochemical localization in rat brain of affinity
      purified anti-GluR3 (glutamate receptor) antibodies from two patients with
      Rasmussen encephalitis (RE) and from immunized rabbits. The distribution of
      immunolabeling was similar using antibodies from rabbits and patients with RE. No
      electrophysiologic responses were elicited from acutely dissociated kainate
      responsive neurons isolated from rat brain when these antibodies were applied.
      These findings show that anti-GluR3 antibodies purified from patients with RE
      bind to specific regions of the CNS but do not act through an excitotoxic
      mechanism.

PMID- 11468322
TI  - Incomplete penetrance with normal MRI in a woman with germline mutation of the
      DCX gene.
AB  - X-linked isolated lissencephaly sequence (ILS) and subcortical band heterotopia
      are allelic human disorders associated with mutations of the DCX gene in both
      familial and sporadic forms. The authors describe a large Sardinian family in
      which three brothers with ILS have a missense mutation of the DCX gene. Their
      mother, a nonmosaic carrier, has a normal phenotype and cranial MRI. Skewed X
      inactivation in the lymphocytes was also ruled out. This is the first report of
      an asymptomatic carrier of a DCX mutation likely due to apparent nonpenetrance.

PMID- 11468323
TI  - Seizure outcome after functional hemispherectomy for malformations of cortical
      development.
AB  - MRI features were correlated with postsurgical seizure outcome in patients with
      hemispheric malformations of cortical development (MCD). After functional
      hemispherectomy, 5 of 6 patients (83%) with hemimegalencephaly had persistent,
      although markedly improved, seizures; 5 of 6 patients (83%) with relative
      preservation of part of one lobe or atrophy were seizure free. Hemimegalencephaly
      and other types of hemispheric MCD appear to differ in prognosis for freedom from
      seizures after functional hemispherectomy.

PMID- 11468324
TI  - Increased von Willebrand factor in migraine.
AB  - The authors determined von Willebrand factor (vWF) in 63 persons with migraine,
      11 persons with migraine and prior stroke, and 35 frequency-matched controls.
      Additional studies were done in a subset with migraine without aura who were
      headache free for >7 days. Migraineurs with prior stroke had significantly higher
      vWF antigen (170% versus 106%) and activity (162% versus 108%) than the control
      group. vWF antigen (126%) and activity (130%) were also significantly higher in
      migraineurs without stroke. Multimers and protease activity were normal in the
      interictal subset.

PMID- 11468325
TI  - Lack of an association between cystatin C gene polymorphisms in Japanese patients
      with Alzheimer's disease.
AB  - Associations between polymorphisms of the cystatin C gene (CST3) at 5' flanking
      region and exon 1 in Caucasian patients with late onset AD and exon 1 in a US
      study of late onset AD have been reported. Clinically diagnosed Japanese patients
      with AD and Japanese normal control subjects were assessed for the presence of
      polymorphisms of CST3. The authors could not confirm the previously reported
      association between CST3 polymorphisms and AD in Japan. Age had no effect on the
      CST3 genotype.

PMID- 11468326
TI  - Temozolomide chemotherapy in recurrent oligodendroglioma.
AB  - The authors determined the tolerance, response rate, and duration of recurrent
      anaplastic oligodendroglioma in 30 patients to temozolomide given orally at 150
      to 200 mg/m2 on days 1 through 5 in cycles of 28 days. Nine patients responded: 7
      of 27 patients (26%) treated with temozolomide after prior PCV chemotherapy and 2
      of 3 chemotherapy-naive patients (both complete response). Median time to
      progression in responding patients was 13 months. Temozolomide shows promise and
      has an acceptable safety profile in recurrent anaplastic oligodendroglial tumors.
      Patients not responding to PCV may respond to temozolomide.

PMID- 11468327
TI  - Increased serum levels of interleukin-18 in patients with multiple sclerosis.
AB  - Serum but not CSF concentrations of the interferon-gamma-inducing cytokine
      interleukin (IL)-18 were significantly augmented in patients with MS as compared
      to both healthy controls and patients with other neurologic diseases. Patients
      with MS with secondary chronic progressive disease had significantly higher serum
      levels than those with relapsing remitting MS. In the latter group, IL-18 levels
      were higher in patients with acute exacerbation as compared to those with stable
      disease.

PMID- 11468328
TI  - Limbic encephalitis associated with recurrent thymoma: a postmortem study.
AB  - The authors report an autopsied patient with limbic encephalitis and recurrent
      thymoma. The immunohistochemical study showed selective depositions of
      immunoglobulin G on the neurons in the limbic system and the tumor cells of the
      recurrent thymoma. The immunoblotting study detected two types of antibodies that
      react with the human brain, rat brain, and rat thymus.

PMID- 11468329
TI  - Spectrum of myelopathies in HIV seropositive South African patients.
AB  - The authors determined the cause of myelopathies in 33 HIV seropositive
      individuals in KwaZulu/Natal, South Africa. The main associations were with human
      T-cell lymphotrophic virus-I, tuberculosis, herpes zoster, and syphilis. A novel
      association with probable bilharziasis was noted. Only one case of vacuolar
      myelopathy was identified. Opportunistic infections will probably persist until
      routine antiretroviral therapy becomes widely available in South Africa.

PMID- 11468330
TI  - Acute, chronic, and recurrent varicella zoster virus neuropathy without zoster
      rash.
AB  - The authors report three patients with acute, chronic, and recurrent neuropathy
      associated with varicella zoster virus (VZV) infection but without zoster rash.
      CSF of all three patients contained VZV immunoglobulin G antibody, but not herpes
      simplex virus. In two patients, serum/CSF ratios of VZV immunoglobulin G were
      reduced compared to normal ratios for immunoglobulin G and albumin, and one
      patient also had VZV immunoglobulin M in CSF. All three patients received
      antiviral therapy and improved. The diagnosis of nervous system infection by VZV
      may be confirmed by the presence of antibody to VZV in CSF even without
      detectable VZV DNA.

PMID- 11468331
TI  - Two-octapeptide repeat deletion of prion protein associated with rapidly
      progressive dementia.
AB  - Insertions of integral numbers of an octapeptide repeat in the prion protein gene
      are pathogenic mutations associated with inherited prion diseases. Conversely,
      deletions of a single octapeptide repeat are found as normal polymorphisms in
      many populations and do not predispose individuals to prion disease. The authors
      report a two-octapeptide repeat deletion in an elderly woman with a rapidly
      progressive dementia consistent with Creutzfeldt-Jakob disease. This mutation was
      absent from more than 3,000 individuals and may be causally related to prion
      disease and represent a novel disease mechanism.

PMID- 11468332
TI  - Postural change of forced vital capacity predicts some respiratory symptoms in
      ALS.
AB  - The detection of respiratory muscle weakness in ALS is necessary to plan
      initiation of noninvasive positive pressure ventilation and begin discussion of
      advanced directives. The authors measured the erect seated and supine forced
      vital capacity (FVC) in 38 patients with ALS and 15 controls. The supine FVC is
      significantly lower and the erect--supine FVC difference is significantly greater
      in patients with complaints of dyspnea, orthopnea, and daytime fatigue.

PMID- 11468333
TI  - The parkin gene is not involved in late-onset Parkinson's disease.
AB  - Mutations in the parkin gene have been reported in patients with early onset PD.
      The authors investigated the parkin gene in 118 patients who had an onset of PD
      after age 45 years: 95 subjects were sporadic patients and 23 subjects were from
      18 families with a probable autosomal recessive inheritance. No pathogenetic
      mutations in the parkin gene were detected either in familial or in sporadic
      patients. Moreover, no differences were found between patients and 100 age
      matched normal controls in the allele and genotype frequencies of four exonic
      parkin polymorphisms.

PMID- 11468334
TI  - The speech disorder of Doc in Walt Disney's "Snow White and the Seven Dwarfs".

PMID- 11468335
TI  - Reversible parkinsonism and MRI diffusion abnormalities in cortical venous
      thrombosis.

PMID- 11468336
TI  - Terson's syndrome following epidural saline injection.

PMID- 11468337
TI  - The cystatin C polymorphism is not associated with early onset Alzheimer's
      disease.

PMID- 11468338
TI  - Improvement of stiff-person syndrome with tiagabine.

PMID- 11468339
TI  - Selegiline and mortality in subjects with Parkinson's disease: a longitudinal
      community study.

PMID- 11468340
TI  - Prion codon 129 homozygosity and sporadic inclusion body myositis.

PMID- 11468341
TI  - Spatial discrimination is abnormal in focal hand dystonia.

PMID- 11468342
TI  - Hydrocarbon exposure and Parkinson's disease.

PMID- 11468344
TI  - Identification of overlapping but distinct cAMP and cGMP interaction sites with
      cyclic nucleotide phosphodiesterase 3A by site-directed mutagenesis and molecular
      modeling based on crystalline PDE4B.
AB  - Cyclic nucleotide phosphodiesterase 3A (PDE3A) hydrolyzes cAMP to AMP, but is
      competitively inhibited by cGMP due to a low k(cat) despite a tight K(m). Cyclic
      AMP elevation is known to inhibit all pathways of platelet activation, and thus
      regulation of PDE3 activity is significant. Although cGMP elevation will inhibit
      platelet function, the major action of cGMP in platelets is to elevate cAMP by
      inhibiting PDE3A. To investigate the molecular details of how cGMP, a similar but
      not identical molecule to cAMP, behaves as an inhibitor of PDE3A, we constructed
      a molecular model of the catalytic domain of PDE3A based on homology to the
      recently determined X-ray crystal structure of PDE4B. Based on the excellent fit
      of this model structure, we mutated nine amino acids in the putative catalytic
      cleft of PDE3A to alanine using site-directed mutagenesis. Six of the nine
      mutants (Y751A, H840A, D950A, F972A, Q975A, and F1004A) significantly decreased
      catalytic efficiency, and had k(cat)/K(m) less than 10% of the wild-type PDE3A
      using cAMP as substrate. Mutants N845A, F972A, and F1004A showed a 3- to 12-fold
      increase of K(m) for cAMP. Four mutants (Y751A, H840A, D950A, and F1004A) had a 9
      to 200-fold increase of K(i) for cGMP in comparison to the wild-type PDE3A.
      Studies of these mutants and our previous study identified two groups of amino
      acids: E866 and F1004 contribute commonly to both cAMP and cGMP interactions
      while N845, E971, and F972 residues are unique for cAMP and the residues Y751,
      H836, H840, and D950 interact with cGMP. Therefore, our results provide
      biochemical evidence that cGMP interacts with the active site residues
      differently from cAMP.

PMID- 11468345
TI  - The N-terminal portion of mature aldehyde dehydrogenase affects protein folding
      and assembly.
AB  - Human liver cytosolic (ALDH1) and mitochondrial (ALDH2) aldehyde dehydrogenases
      are both encoded in the nucleus and synthesized in the cytosol. ALDH1 must fold
      in the cytosol, but ALDH2 is first synthesized as a precursor and must remain
      unfolded during import into mitochondria. The two mature forms share high
      identity (68%) at the protein sequence level except for the first 21 residues
      (14%); their tertiary structures were found to be essentially identical. ALDH1
      folded faster in vitro than ALDH2 and could assemble to tetramers while ALDH2
      remained as monomers. Import assay was used as a tool to study the folding status
      of ALDH1 and ALDH2. pALDH1 was made by fusing the presequence of precursor ALDH2
      to the N-terminal end of ALDH1. Its import was reduced about 10-fold compared to
      the precursor ALDH2. The exchange of the N-terminal 21 residues from the mature
      portion altered import, folding, and assembly of precursor ALDH1 and precursor
      ALDH2. More of chimeric ALDH1 precursor was imported into mitochondria compared
      to its parent precursor ALDH1. The import of chimeric ALDH2 precursor, the
      counterpart of chimeric ALDH1 precursor, was reduced compared to its parent
      precursor ALDH2. Mature ALDH1 proved to be more stable against urea denaturation
      than ALDH2. Urea unfolding improved the import of precursor ALDH1 and the
      chimeric precursors but not precursor ALDH2, consistent with ALDH1 and the
      chimeric ALDHs being more stable than ALDH2. The N-terminal segment of the mature
      protein, and not the presequence, makes a major contribution to the folding,
      assembly, and stability of the precursor and may play a role in folding and hence
      the translocation of the precursor into mitochondria.

PMID- 11468346
TI  - Probing the surface of a sweet protein: NMR study of MNEI with a paramagnetic
      probe.
AB  - The design of safe sweeteners is very important for people who are affected by
      diabetes, hyperlipemia, and caries and other diseases that are linked to the
      consumption of sugars. Sweet proteins, which are found in several tropical
      plants, are many times sweeter than sucrose on a molar basis. A good
      understanding of their structure-function relationship can complement traditional
      SAR studies on small molecular weight sweeteners and thus help in the design of
      safe sweeteners. However, there is virtually no sequence homology and very little
      structural similarity among known sweet proteins. Studies on mutants of monellin,
      the best characterized of sweet proteins, proved not decisive in the localization
      of the main interaction points of monellin with its receptor. Accordingly, we
      resorted to an unbiased approach to restrict the search of likely areas of
      interaction on the surface of a typical sweet protein. It has been recently shown
      that an accurate survey of the surface of proteins by appropriate paramagnetic
      probes may locate interaction points on protein surface. Here we report the
      survey of the surface of MNEI, a single chain monellin, by means of a
      paramagnetic probe, and a direct assessment of bound water based on an
      application of ePHOGSY, an NMR experiment that is ideally suited to detect
      interactions of small ligands to a protein. Detailed surface mapping reveals the
      presence, on the surface of MNEI, of interaction points that include residues
      previously predicted by ELISA tests and by mutagenesis.

PMID- 11468347
TI  - Structural basis for chloramphenicol tolerance in Streptomyces venezuelae by
      chloramphenicol phosphotransferase activity.
AB  - Streptomyces venezuelae synthesizes chloramphenicol (Cm), an inhibitor of
      ribosomal peptidyl transferase activity, thereby inhibiting bacterial growth. The
      producer escapes autoinhibition by its own secondary metabolite through
      phosphorylation of Cm by chloramphenicol phosphotransferase (CPT). In addition to
      active site binding, CPT binds its product 3-phosphoryl-Cm, in an alternate
      product binding site. To address the mechanisms of Cm tolerance of the producer,
      the crystal structures of CPT were determined in complex with either the
      nonchlorinated Cm (2-N-Ac-Cm) at 3.1 A resolution or the antibiotic's immediate
      precursor, the p-amino analog p-NH(2)-Cm, at 2.9 A resolution. Surprisingly, p
      NH(2)-Cm binds CPT in a novel fashion. Additionally, neither 2-N-Ac-Cm nor p
      NH(2)-Cm binds to the secondary product binding site.

PMID- 11468348
TI  - Crystal structure of an anti-interleukin-2 monoclonal antibody Fab complexed with
      an antigenic nonapeptide.
AB  - The three-dimensional structure of the Fab fragment of a monoclonal antibody
      (LNKB-2) to human interleukin-2 (IL-2) complexed with a synthetic antigenic
      nonapeptide, Ac-Lys-Pro-Leu-Glu-Glu-Val-Leu-Asn-Leu-OMe, has been determined at
      3.0 A resolution. In the structure, four out of the six hypervariable loops of
      the Fab (complementarity determining regions [CDRs] L1, H1, H2, and H3) are
      involved in peptide association through hydrogen bonding, salt bridge formation,
      and hydrophobic interactions. The Tyr residues in the Fab antigen binding site
      play a major role in antigen-antibody recognition. The structures of the
      complexed and uncomplexed Fab were compared. In the antigen binding site the CDR
      L1 loop of the antibody shows the largest structural changes upon peptide
      binding. The peptide adopts a mostly alpha-helical conformation similar to that
      in the epitope fragment 64-72 of the IL-2 antigen. The side chains of residues
      Leu 66, Val 69, and Leu 70, which are shielded internally in the IL-2 structure,
      are involved in interactions with the Fab in the complex studied. This indicates
      that antibody-antigen complexation involves a significant rearrangement of the
      epitope-containing region of the IL-2 with retention of the alpha-helical
      character of the epitope fragment.

PMID- 11468349
TI  - Fluorescence correlation spectroscopy as a method for assessment of interactions
      between phage displaying antibodies and soluble antigen.
AB  - Phage display is widely used for expression of combinatorial libraries, not least
      for protein engineering purposes. Precise selection at the single molecule level
      will provide an improved tool for generating proteins with complex and distinct
      properties from large molecular libraries. To establish such an improved
      selection system, we here report the detection of specific interactions between
      phage with displayed antibody fragments and fluorescently labeled soluble antigen
      based on Fluorescence Correlation Spectroscopy (FCS). Our novel strategy
      comprises the use of two separate fluorochromes for detection of the phage
      antigen complex, either with labeled antiphage antibody or using a labeled
      antigen. As a model system, we studied a human monoclonal antibody to the
      hepatitis-C virus (HCV) envelope protein E2 and its cognate antigen (rE2 or
      rE1/E2). We could thus assess the specific interactions and determine the
      fraction of specific versus background phage (26% specific phage). Aggregation of
      these particular antigens made it difficult to reliably utilize the full
      potential of cross-correlation studies using the two labels simultaneously.
      However, with true monomeric proteins, this will certainly be possible, offering
      a great advantage in a safer and highly specific detection system.

PMID- 11468350
TI  - Modeling of the structural features of integral-membrane proteins reverse
      environment prediction of integral membrane protein structure (REPIMPS).
AB  - The Profiles-3D application, an inverse-folding methodology appropriate for water
      soluble proteins, has been modified to allow the determination of structural
      properties of integral-membrane proteins (IMPs) and for testing the validity of
      solved and model structures of IMPs. The modification, known as reverse
      environment prediction of integral membrane protein structure (REPIMPS), takes
      into account the fact that exposed areas of side chains for many residues in IMPs
      are in contact with lipid and not the aqueous phase. This (1) allows lipid
      exposed residues to be classified into the correct physicochemical environment
      class, (2) significantly improves compatibility scores for IMPs whose structures
      have been solved, and (3) reduces the possibility of rejecting a three
      dimensional structure for an IMP because the presence of lipid was not included.
      Validation tests of REPIMPS showed that it (1) can locate the transmembrane
      domain of IMPs with single transmembrane helices more frequently than a range of
      other methodologies, (2) can rotationally orient transmembrane helices with
      respect to the lipid environment and surrounding helices in IMPs with multiple
      transmembrane helices, and (3) has the potential to accurately locate
      transmembrane domains in IMPs with multiple transmembrane helices. We conclude
      that correcting for the presence of the lipid environment surrounding the
      transmembrane segments of IMPs is an essential step for reasonable modeling and
      verification of the three-dimensional structures of these proteins.

PMID- 11468351
TI  - High stability of a ferredoxin from the hyperthermophilic archaeon A. ambivalens:
      involvement of electrostatic interactions and cofactors.
AB  - The ferredoxin from the thermophilic archaeon Acidianus ambivalens is a small
      monomeric seven-iron protein with a thermal midpoint (T(m)) of 122 degrees C (pH
      7). To gain insight into the basis of its thermostability, we have characterized
      unfolding reactions induced chemically and thermally at various pHs. Thermal
      unfolding of this ferredoxin, in the presence of various guanidine hydrochloride
      (GuHCl) concentrations, yields a linear correlation between unfolding enthalpies
      (DeltaH[T(m)]) and T(m) from which an upper limit for the heat capacity of
      unfolding (DeltaC(P)) was determined to be 3.15 +/- 0.1 kJ/(mole * K). Only by
      the use of the stronger denaturant guanidine thiocyanate (GuSCN) is unfolding of
      A. ambivalens ferredoxin at pH 7 (20 degrees C) observed ([GuSCN](1/2) = 3.1 M;
      DeltaG(U)[H(2)O] = 79 +/- 8 kJ/mole). The protein is, however, less stable at low
      pH: At pH 2.5, T(m) is 64 +/- 1 degrees C, and GuHCl-induced unfolding shows a
      midpoint at 2.3 M (DeltaG(U)[H(2)O] = 20 +/- 1 kJ/mole). These results support
      that electrostatic interactions contribute significantly to the stability.
      Analysis of the three-dimensional molecular model of the protein shows that there
      are several possible ion pairs on the surface. In addition, ferredoxin
      incorporates two iron-sulfur clusters and a zinc ion that all coordinate
      deprotonated side chains. The zinc remains bound in the unfolded state whereas
      the iron-sulfur clusters transiently form linear three-iron species (in pH range
      2.5 to 10), which are associated with the unfolded polypeptide, before their
      complete degradation.

PMID- 11468352
TI  - Novel inter-protein cross-link identified in the GGH-ecotin D137Y dimer.
AB  - In the presence of a suitable oxidizing agent, the Ni(II) complex of glycyl
      glycyl-histidine (GGH) mediates efficient and specific oxidative protein cross
      linking. The fusion of GGH to the N terminus of a protein allows for the cross
      linking reagent to be delivered in a site-specific fashion, making this system
      extremely useful for analyzing protein-protein contacts in complicated mixtures
      of biomolecules. Tyrosine residues have been postulated to be the primary amino
      acid target of this reaction, and using the dimeric serine protease inhibitor
      ecotin, we previously demonstrated that engineering a tyrosine at the protein
      interface of a dimer dramatically increased cross-linking efficiency. Cross
      linking increased four-fold for GGH-ecotin D137Y in comparison to wild-type GGH
      ecotin, presumably through bityrosine formation at the dimer interface. Here we
      report the first complete structural analysis of the cross-linked GGH-ecotin
      D137Y dimer. Using a combination of mass spectrometric and chemical
      derivatization methods, a sole novel cross-link between the N-terminal glycine
      residues and the engineered tyrosine at position 137 has been characterized. The
      dimer cross-link is localized to a single site without other protein
      modifications, but different reaction pathways produce structurally related
      products. We propose a mechanism that involves covalent bond formation between
      the protein backbone and a dopaquinone moiety derived from a specific tyrosine
      residue. This finding establishes that it is not necessary to have two tyrosine
      residues within close proximity in the protein interface to obtain high protein
      cross-linking yields, and suggests that the cross-linking reagent may be of more
      general utility than previously thought.

PMID- 11468353
TI  - Modeling of the bacterial luciferase-flavin mononucleotide complex combining
      flexible docking with structure-activity data.
AB  - Although the crystal structure of Vibrio harveyi luciferase has been elucidated,
      the binding sites for the flavin mononucleotide and fatty aldehyde substrates are
      still unknown. The determined location of the phosphate-binding site close to Arg
      107 on the alpha subunit of luciferase is supported here by point mutagenesis.
      This information, together with previous structure-activity data for the length
      of the linker connecting the phosphate group to the isoalloxazine ring represent
      important characteristics of the luciferase-bound conformation of the flavin
      mononucleotide. A model of the luciferase-flavin complex is developed here using
      flexible docking supplemented by these structural constraints. The location of
      the phosphate moiety was used as the anchor in a flexible docking procedure
      performed by conformation search by using the Monte Carlo minimization approach.
      The resulting databases of energy-ranked feasible conformations of the luciferase
      complexes with flavin mononucleotide, omega-phosphopentylflavin, omega
      phosphobutylflavin, and omega-phosphopropylflavin were filtered according to the
      structure-activity profile of these analogs. A unique model was sought not only
      on energetic criteria but also on the geometric requirement that the
      isoalloxazine ring of the active flavin analogs must assume a common orientation
      in the luciferase-binding site, an orientation that is also inaccessible to the
      inactive flavin analog. The resulting model of the bacterial luciferase-flavin
      mononucleotide complex is consistent with the experimental data available in the
      literature. Specifically, the isoalloxazine ring of the flavin mononucleotide
      interacts with the Ala 74-Ala 75 cis-peptide bond as well as with the Cys 106
      side chain in the alpha subunit of luciferase. The model of the binary complex
      reveals a distinct cavity suitable for aldehyde binding adjacent to the
      isoalloxazine ring and flanked by other key residues (His 44 and Trp 250)
      implicated in the active site.

PMID- 11468354
TI  - How common is the funnel-like energy landscape in protein-protein interactions?
AB  - The goal of this study is to verify the concept of the funnel-like intermolecular
      energy landscape in protein-protein interactions by use of a series of
      computational experiments. Our preliminary analysis revealed the existence of the
      funnel in many protein-protein interactions. However, because of the
      uncertainties in the modeling of these interactions and the ambiguity of the
      analysis procedures, the detection of the funnels requires detailed quantitative
      approaches to the energy landscape analysis. A number of such approaches are
      presented in this study. We show that the funnel detection problem is equivalent
      to a problem of distinguishing between distributions of low-energy intermolecular
      matches in the funnel and in the low-frequency landscape fluctuations. If the
      fluctuations are random, the decision about whether the minimum is the funnel is
      equivalent to determining whether this minimum is significantly different from a
      would-be random one. A database of 475 nonredundant cocrystallized protein
      protein complexes was used to re-dock the proteins by use of smoothed potentials.
      To detect the funnel, we developed a set of sophisticated models of random
      matches. The funnel was considered detected if the binding area was more
      populated by the low-energy docking predictions than by the matches generated in
      the random models. The number of funnels detected by use of different random
      models varied significantly. However, the results confirmed that the funnel may
      be the general feature in protein-protein association.

PMID- 11468355
TI  - Computational analysis of binding of P1 variants to trypsin.
AB  - The binding of P1 variants of bovine pancreatic trypsin inhibitor (BPTI) to
      trypsin has been investigated by means of molecular dynamics simulations. The
      specific interaction formed between the amino acid at the primary binding (P1)
      position of the binding loop of BPTI and the specificity pocket of trypsin was
      estimated by use of the linear interaction energy (LIE) method. Calculations for
      13 of the naturally occurring amino acids at the P1 position were carried out,
      and the results obtained were found to correlate well with the experimental
      binding free energies. The LIE calculations rank the majority of the 13 variants
      correctly according to the experimental association energies and the mean error
      between calculated and experimental binding free energies is only 0.38 kcal/mole,
      excluding the Glu and Asp variants, which are associated with some uncertainties
      regarding protonation and the possible presence of counter-ions. The three
      dimensional structures of the complex with three of the P1 variants (Asn, Tyr,
      and Ser) included in this study have not at present been solved by any
      experimental techniques and, therefore, were modeled on the basis of experimental
      data from P1 variants of similar size. Average structures were calculated from
      the MD simulations, from which specific interactions explaining the broad
      variation in association energies were identified. The present study also shows
      that explicit treatment of the complex water-mediated hydrogen bonding network at
      the protein-protein interface is of crucial importance for obtaining reliable
      binding free energies. The successful reproduction of relative binding energies
      shows that this type of methodology can be very useful as an aid in rational
      design and redesign of biologically active macromolecules.

PMID- 11468356
TI  - The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just
      an S --> O change.
AB  - Protein-tyrosine phosphatases catalyze the hydrolysis of phosphate monoesters via
      a two-step mechanism involving a covalent phospho-enzyme intermediate.
      Biochemical and site-directed mutagenesis experiments show that the invariant Cys
      residue present in the PTPase signature motif (H/V)CX(5)R(S/T) (i.e., C215 in
      PTP1B) is absolutely required for activity. Mutation of the invariant Cys to Ser
      results in a catalytically inactive enzyme, which still is capable of binding
      substrates and inhibitors. Although it often is assumed that substrate-trapping
      mutants such as the C215S retain, in solution, the structural and binding
      properties of wild-type PTPases, significant differences have been found in the
      few studies that have addressed this issue, suggesting that the mutation may lead
      to structural/conformational alterations in or near the PTP1B binding site.
      Several crystal structures of apo-WT PTP1B, and of WT- and C215S-mutant PTP1B in
      complex with different ligands are available, but no structure of the apo-PTP1B
      C215S has ever been reported. In all previously reported structures, residues of
      the PTPase signature motif have an identical conformation, while residues of the
      WPD loop (a surface loop which includes the catalytic Asp) assume a different
      conformation in the presence or absence of ligand. These observations led to the
      hypothesis that the different spectroscopic and thermodynamic properties of the
      mutant protein may be the result of a different conformation for the WPD loop. We
      report here the structure of the apo-PTP1B C215S mutant, which reveals that,
      while the WPD loop is in the open conformation observed in the apo WT enzyme
      crystal structure, the residues of the PTPases signature motif are in a
      dramatically different conformation. These results provide a structural basis for
      the differences in spectroscopic properties and thermodynamic parameters in
      inhibitor binding observed for the wild-type and mutant enzymes.

PMID- 11468357
TI  - Transthyretin slowly exchanges subunits under physiological conditions: A
      convenient chromatographic method to study subunit exchange in oligomeric
      proteins.
AB  - Transthyretin (TTR) subunits were labeled with a charge-modifying tag to evaluate
      the possibility of subunit exchange between tetramers under physiological
      conditions. Starting with a mixture of two TTR homotetramers, one having all
      subunits tagged at the N termini and the other composed of untagged subunits,
      heterotetramer formation as a function of time and temperature was evaluated
      using ion exchange chromatography. The data indicate that the subunit exchange
      can occur under native conditions at physiological pH in vitro, albeit slowly.
      Wild-type TTR exchanges subunits on a timescale of days at 37 degrees C and on a
      timescale of hours at 4 degrees C. The familial amyloid polyneuropathy-associated
      variant V30M exchanges subunits at the same rate as wild-type TTR at 4 degrees C
      but slower and less efficiently at 37 degrees C. Small molecule tetramer
      stabilizers abolish TTR subunit exchange, supporting a dissociative mechanism.

PMID- 11468358
TI  - Binding of a fibrinogen mimetic stabilizes integrin alphaIIbbeta3's open
      conformation.
AB  - The platelet integrin alphaIIbbeta3 is representative of a class of heterodimeric
      receptors that upon activation bind extracellular macromolecular ligands and form
      signaling clusters. This study examined how occupancy of alphaIIbbeta3's
      fibrinogen binding site affected the receptor's solution structure and stability.
      Eptifibatide, an integrin antagonist developed to treat cardiovascular disease,
      served as a high-affinity, monovalent model ligand with fibrinogen-like
      selectivity for alphaIIbbeta3. Eptifibatide binding promptly and reversibly
      perturbed the conformation of the alphaIIbbeta3 complex. Ligand-specific
      decreases in its diffusion and sedimentation coefficient were observed at near
      stoichiometric eptifibatide concentrations, in contrast to the receptor
      perturbing effects of RGD ligands that we previously observed only at a 70-fold
      molar excess. Eptifibatide promoted alphaIIbbeta3 dimerization 10-fold more
      effectively than less selective RGD ligands, as determined by sedimentation
      equilibrium. Eptifibatide-bound integrin receptors displayed an ectodomain
      separation and enhanced assembly of dimers and larger oligomers linked through
      their stalk regions, as seen by transmission electron microscopy. Ligation with
      eptifibatide protected alphaIIbbeta3 from SDS-induced subunit dissociation, an
      effect on electrophoretic mobility not seen with RGD ligands. Despite its
      distinct cleft, the open conformer resisted guanidine unfolding as effectively as
      the ligand-free integrin. Thus, we provide the first demonstration that binding a
      monovalent ligand to alphaIIbbeta3's extracellular fibrinogen-recognition site
      stabilizes the receptor's open conformation and enhances self-association through
      its distant transmembrane and/or cytoplasmic domains. By showing how eptifibatide
      and RGD peptides, ligands with distinct binding sites, each affects
      alphaIIbbeta3's conformation, our findings provide new mechanistic insights into
      ligand-linked integrin activation, clustering and signaling.

PMID- 11468359
TI  - Mercurial sensitivity of aquaporin 1 endofacial loop B residues.
AB  - The water channel protein aquaporin-1 (AQP1) has two asparagine-proline-alanine
      (NPA) repeats on loops B and E. From recent structural information, these loops
      are on opposite sides of the membrane and meet to form a pore. We replaced the
      mercury-sensitive residue cysteine 189 in AQP1 by serine to obtain a mercury
      insensitive template (C189S). Subsequently, we substituted three consecutive
      cysteines for residues 71-73 near the first NPA repeat (76-78) in intracellular
      loop B, and investigated whether they were accessible to extracellular
      mercurials. AQP1 and its mutants were expressed in Xenopus laevis oocytes, and
      the osmotic permeability (P(f)) of the oocytes was determined. C189S had wild
      type P(f) but was not sensitive to HgCl(2). Expression of all three C189S
      cysteine mutants resulted in increased P(f), and all three mutants regained
      mercurial sensitivity. These results, especially the inhibitions by the large
      mercurial p-chloromercunbenzene-sulfonic acid (pCMBS) ( approximately 6A wide),
      suggest that residues 71-73 at the pore are accessible to extracellular
      mercurials. A 30-ps molecular dynamics simulation (at 300 K) starting with
      crystallographic coordinates of AQP1 showed that the width of the pore bottleneck
      (between Connolly surfaces) can vary (w(avg) = 3.9 A, sigma = 0.75; hydrated
      AQP1). Thus, although the pore width would be > or = 6 A only for 0.0026 of the
      time, this might suffice for pCMBS to reach residues 71-73. Alternative
      explanations such as passage of pCMBS across the AQP1 tetramer center or other
      unspecified transmembrane pathways cannot be excluded.

PMID- 11468360
TI  - Reversible formation of on-pathway macroscopic aggregates during the folding of
      maltose binding protein.
AB  - Maltose binding protein (MBP) is widely used as a model for protein folding and
      export studies. We show here that macroscopic aggregates form transiently during
      the refolding of MBP at micromolar protein concentrations. Disaggregation occurs
      spontaneously without any aid, and the refolded material has structure and
      activity identical to those of the native, nondenatured protein. A considerable
      fraction of protein undergoing folding partitions into the aggregate phase and
      can be manually separated from the soluble phase by centrifugation. The separated
      MBP precipitate can be resolubilized and yields active, refolded protein. This
      demonstrates that both the soluble and aggregate phases contribute to the final
      yield of refolded protein. SecB, the cognate Escherichia coli cytosolic chaperone
      in vivo for MBP, reduces but does not entirely prevent aggregation, whereas GroEL
      and a variety of other control proteins have no effect. Kinetic studies using a
      variety of spectroscopic probes show that aggregation occurs through a collapsed
      intermediate with some secondary structure. The aggregate formed during refolding
      can convert directly to a near native state without going through the unfolded
      state. Further, optical and electron microscopic studies indicate that the MBP
      precipitate is not an amyloid.

PMID- 11468361
TI  - Molecular mimicry of substrate oxygen atoms by water molecules in the beta
      amylase active site.
AB  - Soybean beta-amylase (EC 3.2.1.2) has been crystallized both free and complexed
      with a variety of ligands. Four water molecules in the free-enzyme catalytic
      cleft form a multihydrogen-bond network with eight strategic residues involved in
      enzyme-ligand hydrogen bonds. We show here that the positions of these four water
      molecules are coincident with the positions of four potential oxygen atoms of the
      ligands within the complex. Some of these waters are displaced from the active
      site when the ligands bind to the enzyme. How many are displaced depends on the
      shape of the ligand. This means that when one of the four positions is not
      occupied by a ligand oxygen atom, the corresponding water remains. We studied the
      functional/structural role of these four waters and conclude that their presence
      means that the conformation of the eight side chains is fixed in all situations
      (free or complexed enzyme) and preserved from unwanted or forbidden
      conformational changes that could hamper the catalytic mechanism. The water
      structure at the active pocket of beta-amylase is therefore essential for
      providing the ligand recognition process with plasticity. It does not affect the
      protein active-site geometry and preserves the overall hydrogen-bonding network,
      irrespective of which ligand is bound to the enzyme. We also investigated whether
      other enzymes showed a similar role for water. Finally, we discuss the potential
      use of these results for predicting whether water molecules can mimic ligand
      atoms in the active center.

PMID- 11468362
TI  - Involvement of the amino-terminal beta-hairpin of the Aspergillus ribotoxins on
      the interaction with membranes and nonspecific ribonuclease activity.
AB  - Ribotoxins are a family of potent cytotoxic proteins from Aspergillus whose
      members display a high sequence identity (85% for about 150 amino acid residues).
      The three-dimensional structures of two of these proteins, alpha-sarcin and
      restrictocin, are known. They interact with phospholipid bilayers, according to
      their ability to enter cells, and cleave a specific phosphodiester bond in the
      large subunit of ribosome thus inhibiting protein biosynthesis. Two
      nonconservative sequence changes between these proteins are located at the amino
      terminal beta-hairpin of alpha-sarcin, a characteristic structure that is absent
      in other nontoxic structurally related microbial RNases. These two residues of
      alpha-sarcin, Lys 11 and Thr 20, have been substituted with the equivalent amino
      acids in restrictocin. The single mutants (K11L and T20D) and the corresponding
      K11L/T20D double mutant have been produced in Escherichia coli and purified to
      homogeneity. The spectroscopic characterization of the purified proteins reveals
      that the overall native structure is preserved. The ribonuclease and lipid
      perturbing activities of the three mutants and restrictocin have been evaluated
      and compared with those of alpha-sarcin. These proteins exhibit the same ability
      to specifically inactivate ribosomes, although they show different activity
      against nonspecific substrate analogs such as poly(A). The mutant variant K11L
      and restrictocin display a lower phospholipid-interacting ability correlated with
      a decreased cytotoxicity. The results obtained are interpreted in terms of the
      involvement of the amino-terminal beta-hairpin in the interaction with both
      membranes and polyadenylic acid.

PMID- 11468363
TI  - Binding of phosphate and pyrophosphate ions at the active site of human
      angiogenin as revealed by X-ray crystallography.
AB  - Human angiogenin (Ang) is an unusual homolog of bovine pancreatic RNase A that
      utilizes its ribonucleolytic activity to induce the formation of new blood
      vessels. The pyrimidine-binding site of Ang was shown previously to be blocked by
      glutamine 117, indicating that Ang must undergo a conformational change to bind
      and cleave RNA. The mechanism and nature of this change are not known, and no Ang
      inhibitor complexes have been characterized structurally thus far. Here, we
      report crystal structures for the complexes of Ang with the inhibitors phosphate
      and pyrophosphate, and the structure of the complex of the superactive Ang
      variant Q117G with phosphate, all at 2.0 A resolution. Phosphate binds to the
      catalytic site of both Ang and Q117G in essentially the same manner observed in
      the RNase A-phosphate complex, forming hydrogen bonds with the side chains of His
      13, His 114, and Gln 12, and the main chain of Leu 115; it makes an additional
      interaction with the Lys 40 ammonium group in the Ang complex. One of the
      phosphate groups of pyrophosphate occupies a similar position. The other
      phosphate extends toward Gln 117, and lies within hydrogen-bonding distance from
      the side-chain amide of this residue as well as the imidazole group of His 13 and
      the main-chain oxygen of Leu 115. The pyrimidine site remains obstructed in all
      three complex structures, that is, binding to the catalytic center is not
      sufficient to trigger the conformational change required for catalytic activity,
      even in the absence of the Gln 117 side chain. The Ang-pyrophosphate complex
      structure suggests how nucleoside pyrophosphate inhibitors might bind to Ang;
      this information may be useful for the design of Ang antagonists as potential
      anti-angiogenic drugs.

PMID- 11468364
TI  - Haspin-like proteins: a new family of evolutionarily conserved putative
      eukaryotic protein kinases.
AB  - Haspin (haploid germ cell-specific nuclear protein kinase) is reported to be a
      serine/threonine kinase that may play a role in cell-cycle cessation and
      differentiation of haploid germ cells. In addition, Haspin mRNA can be detected
      in diploid cell lines and tissues. Here, Haspin-like proteins are identified in
      several major eukaryotic phyla-including yeasts, plants, flies, fish, and mammals
      and an extended group in Caenorhabditis elegans. The Haspin-like proteins have a
      complete but divergent eukaryotic protein kinase domain sequence. Although
      clearly related to one another and to other eukaryotic protein kinases, the
      Haspin-related proteins lack conservation of a subset of residues that are almost
      invariant in known kinases and possess distinctive inserted regions. In fact,
      phylogenetic analysis indicates that the Haspin-like proteins form a novel
      eukaryotic protein kinase family distinct from those previously defined. The
      identification of related proteins in model organisms provides some initial
      insight into their functional properties and will provide new experimental
      avenues by which to determine the function of the Haspin proteins in mammalian
      cells.

PMID- 11468365
TI  - Refolding kinetics of cytochrome c(551) reveals a mechanistic difference between
      urea and guanidine.
AB  - The energetic parameters for the folding of small globular proteins can be very
      different if derived from guanidine hydrochloride (GdnHCl) or urea denaturation
      experiments. A study of the equilibrium and kinetics of the refolding of wild
      type (wt) cytochrome c(551) (cyt c(551)) from Pseudomonas aeruginosa and of two
      site-directed mutants (E70Q and E70V) shows that the nonionic nature of urea
      reveals the role of a salt bridge between residues E70 and K10 on the transition
      state, which is otherwise completely masked in GdnHCl experiments. Mixed
      denaturant refolding experiments allow us to conclude that the masking effect of
      GdnHCl is complete at fairly low GdnHCl concentrations ( congruent with 0.1 M).
      The fact that potassium chloride is unable to reproduce this quenching effect,
      together with the results obtained on the mutants, suggests a specific binding of
      the Gdn(+) cation, which involves the E70-K10 ion pair in wt cyt c(551). We
      propose, therefore, a simple kinetic test to obtain a mechanistic interpretation
      of nonlinear dependences of DeltaG(w) on GdnHCl concentration on the basis of
      kinetic refolding experiments in the presence of both denaturants.

PMID- 11468366
TI  - In memoriam: Professor G.N. Ramachandran (1922-2001).
AB  - Few scientists contribute an idea of such clarity and power that it appears in
      all the discipline's textbooks and bears the author's name. For the contribution
      to be relevant and universally employed almost forty years after it first
      appeared is even less common. Structural biology lost the author of such an idea
      with the death of G.N. Ramachandran, whose picture appears on the cover of this
      issue of Protein Science. His seminal contribution is described in remembrances
      of Professor Ramachandran's life and career by colleague and co-author of the
      1963 paper, C. Ramakrishnan. A perspective by George D. Rose follows, which
      articulates the enduring impact of that work.

PMID- 11468367
TI  - Perspective.

PMID- 11468369
TI  - Transition from the incommensurately modulated structure to the lock-in phase in
      Co-akermanite.
AB  - The adaptation of the incommensurate structure modulation in Ca(2)CoSi(2)O(7)
      (dicalcium cobalt disilicate) single crystals to decreasing temperature has been
      examined using in situ high-resolution transmission electron microscopy and
      electron diffraction. The transition from the incommensurate to the commensurate
      lock-in phase of Co-akermanite exhibits a pronounced hysteresis of a highly
      strained metastable state with a characteristic microdomain morphology. A network
      of domain walls surrounding single orientation domains develops out of the room
      temperature tartan pattern, the domains increase in size and their alignment
      changes from crystallographic to random. At 100 K the phase transition becomes
      almost complete. In parallel, the evolution of the modulation structure can be
      described by a change from a loose arrangement of octagonal tilings into a close
      packed configuration of overlapping octagons in the commensurate low-temperature
      lock-in phase. Thereby, the octagon represents the ordered distribution of low
      coordinated Ca clusters within a nanodomain extending over 4 x 4 subunits, on
      average [Riester et al. (2000). Z. Kristallogr. 215, 102--109]. The modulation
      wavevector was found to change from q(1,2) = 0.295 (a* +/- b*) at 300 K to q(1,2)
      = 0.320 (a* +/- b*) at 100 K.

PMID- 11468370
TI  - Structure refinement of the layered composite crystal Sc2B1.1C3.2 in a five
      dimensional formalism.
AB  - The crystal structure of a layered compound Sc(2)B(1.1)C(3.2), scandium boride
      carbide (M(r) = 140.43), has been re-refined as a commensurate composite crystal
      using 1795 single-crystal X-ray diffraction intensities with I > 2 sigma(I)
      collected by Shi, Leithe-Jasper, Bourgeois, Bando & Tanaka [(1999), J. Solid
      State Chem. 148, 442--449]. The crystal is composed of two layered subsystem
      structures, i.e. Sc--C--Sc sandwiches and graphite-like layers of the composition
      B(1/3)C(2/3). The structure refinement was performed in a five-dimensional
      formalism based on the trigonal superspace group P3m1(p00)(0p0)0m0. The unit cell
      and other crystal data are a = b = 3.387 (1), c = 6.703 (2) A, V = 66.59 (1)
      A(3), sigma(1) = (9/7 0 0), sigma(2) = (0 9/7 0), Z = 1, D(x) = 3.501 Mg m(-3).
      Two different three-dimensional sections through the superspace were analyzed,
      corresponding to two different superstructure models, one with P3m1 and the other
      with P3m1. A random distribution of B and C was assumed in the graphite-like
      layer and 41 structural parameters were introduced. R(F)/wR(F) were 0.0533/0.0482
      and 0.0524/0.0476, respectively, for the first and second models. Although the
      difference between these R(F) or wR(F) values was too fine to exclude one of the
      models definitely, the advantages of using a superspace group were obvious. It
      not only brought about better convergence of refinement cycles by virtue of fewer
      parameters, but also gave an insight into the problem of symmetry of the
      superstructure.

PMID- 11468371
TI  - Modulated structure of the pseudohexagonal InFe(1--x--4 delta)Ti(x+3
      delta)O(3+x/2) (x = 0.61) composite crystal.
AB  - The structure of pseudohexagonal-type InFe(1--x--4 delta)Ti(x+3 delta)O(3+x/2) (x
      = 0.61, delta = 0.04), indium iron titanium oxide, was refined on the basis of a
      four-dimensional superspace group. The crystal has a compositely modulated
      structure consisting of two orthorhombic subsystems mutually incommensurate in b.
      The first subsystem InFe(1-x-4 delta)Ti(x+3 delta)O(2) has a delafossite
      structure with lattice parameters a = 5.835 (3), b(1) = 3.349 (1) and c = 12.082
      (7) A. The second subsystem with b(2) = 2.568 (6) A consists of O atoms. The
      superspace group of the overall structure is Ccmm(1, 1.305, 0)s00, which can be
      converted to Amam(0, 0, 0.305)0s0 (No. 63.8). Refinement on 1105 unique
      reflections converged to R = 0.0303 and wR = 0.0325 with 63 structural
      parameters. The structure of the first subsystem is the alternate stacking of an
      edge-shared InO(6) octahedral layer and an Fe/Ti triangle-lattice plane along c.
      A sheet of O atoms in the second subsystem is also extending on the Fe/Ti plane,
      where displacive modulation of atoms is prominent.

PMID- 11468372
TI  - Hexagonal Frank--Kasper phases interpreted as modulated crystals.
AB  - The structures of the hexagonal Frank--Kasper phases F and K, which have been
      described in terms of the aggregation of clusters, are interpreted as modulated
      crystal structures. They are basically composed of two close-packed layers with
      ordered atomic vacancies rotated by 90 degrees to each other about their normal.

PMID- 11468373
TI  - Intergrowth polytypoids as modulated structures: a superspace description of the
      Sr(n)(Nb,Ti)(n)O(3n + 2) compound series.
AB  - A new, unified superspace approach to the structural characterization of the
      perovskite-related Sr(n)(Nb,Ti)(n)O(3n + 2) compound series, strontium
      niobium/titanium oxide, is presented. To a first approximation, the structure of
      any member of this compound series can be described in terms of the stacking of
      (110)-bounded perovskite slabs, the number of atomic layers in a single
      perovskite slab varying systematically with composition. The various composition
      dependent layer-stacking sequences can be interpreted in terms of the structural
      modulation of a common underlying average structure. The average interlayer
      separation distance is directly related to the average structure periodicity
      along the layer stacking direction, while an inherent modulation thereof is
      produced by the presence of different types of layers (particularly vacant
      layers) along this stacking direction. The fundamental atomic modulation is
      therefore occupational and can be described by means of crenel (step-like)
      functions which define occupational atomic domains in the superspace, similarly
      to what occurs for quasicrystals. While in a standard crystallographic approach,
      one must describe each structure (in particular the space group and cell
      parameters) separately for each composition, the proposed superspace model is
      essentially common to the whole compound series. The superspace symmetry group is
      unique, while the primary modulation wavevector and the width of some occupation
      domains vary linearly with composition. For each rational composition, the
      corresponding conventional three-dimensional space group can be derived from the
      common superspace group. The resultant possible three-dimensional space groups
      are in agreement with all the symmetries reported for members of the series. The
      symmetry-breaking phase transitions with temperature observed in many compounds
      can be explained in terms of a change in superspace group, again in common for
      the whole compound series. Inclusion of the incommensurate phases, present in
      many compounds of the series, lifts the analysis into a five-dimensional
      superspace. The various four-dimensional superspace groups reported for this
      incommensurate phase at different compositions are shown to be predictable from a
      proposed five-dimensional superspace group apparently common to the whole
      compound series. A comparison with the scarce number of refined structures in
      this system and the homologous (Nb,Ca)(6)Ti(6)O(20) compound demonstrates the
      suitability of the proposed formalism.

PMID- 11468374
TI  - Ferroelectricity and structure in the YMnO(3) family.
AB  - The 1963 discovery of ferroelectricity in YMnO(3) was accompanied by an
      experimental Curie temperature (T(c)) reported as 913 K; this value was revised
      to 1270 K in the following decade. Subsequently, YInO(3) was shown to be
      isostructural with YMnO(3) and later demonstrated to satisfy the structural
      criteria for ferroelectricity; recent unpublished measurements give T(c)
      (YInO(3)) = 835 (15) K. The experimental T(c) value of 913 K for YMnO(3) is in
      satisfactory agreement with the calculated 1220 (100) K value as derived from a
      very recent structural refinement, the experimental T(c) of 835 (15) K for
      YInO(3) with the calculated 760 (120) K. The full YMnO(3) family includes the
      AMnO(3) subfamily with A = Y, Ho, Er, Tm, Yb, Lu, Sc, In; the AInO(3) subfamily
      with A = Y, Gd, Dy, Ho, Tb; and the AGaO(3) subfamily with A = Y, Ho, Er. The
      T(c) values of six family members with known structure, in addition to YMnO(3)
      and YInO(3), have been structurally derived as 1310 (110) K for ErMnO(3), 1290
      (165) K for LuMnO(3), 1270 (110) K for YbMnO(3), 1220 (105) K for ScMnO(3), 540
      (375) K for InMnO(3) and 1020 (100) K for YGaO(3). The agreement between
      predicted and experimental T(c) values for ErMnO(3), LuMnO(3) and YbMnO(3), in
      addition to that for YMnO(3) and YInO(3), leads to the confident prediction that
      ScMnO(3), InMnO(3) and YGaO(3) are new ferroelectrics. The remaining six members
      of the full YMnO(3) family are also expected to be new ferroelectrics.

PMID- 11468375
TI  - Parametrization of perovskite structures: an ab initio study.
AB  - An overview of the pressure, temperature and chemical composition dependence of
      the lattice distortion in orthorhombic ABO(3) perovskite structures is presented.
      Within the framework of the so-called global parametrization method (GPM) [Thomas
      (1998). Acta Cryst. B54, 585--599] an improved description for the position of
      the A cation in terms of the AO(12) and BO(6) polyhedral volume ratio is
      proposed. The relationship is derived from an extensive ab initio study based on
      the density functional theory. The applicability of the improved GPM in
      combination with ab initio total energy calculations in the prediction of changes
      in the structural distortion under increasing hydrostatic pressure is
      investigated. Test calculations are performed for the geophysically important
      magnesium silicate perovskite and the results are compared with the available
      theoretical and experimental data.

PMID- 11468376
TI  - Structures of copper(II) and manganese(II) di(hydrogen malonate) dihydrate;
      effects of intensity profile truncation and background modelling on structure
      models.
AB  - The crystal structures of the title compounds were determined with net
      intensities I derived via the background-peak-background procedure. Least-squares
      optimizations reveal differences between the low-order (0 < s < 0.7 A(-1)) and
      high-order (0.7 < s < 1.0 A(-1)) structure models. The scale factors indicate
      discrepancies of up to 10% between the low-order and high-order reflection
      intensities. This observation is compound independent. It reflects the scan-angle
      induced truncation error, because the applied scan angle (0.8 + 2.0 tan theta)
      degrees underestimates the wavelength dispersion in the monochromated X-ray beam.
      The observed crystal structures show pseudo-I-centred sublattices for three of
      its non-H atoms in the asymmetric unit. Our selection of observed intensities (I
      > 3 sigma) stresses that pseudo-symmetry. Model refinements on individual data
      sets with (h + k + l) = 2n and (h + k + l) = 2n + 1 illustrate the lack of model
      robustness caused by that pseudo-symmetry. To obtain a better balanced data set
      and thus a more robust structure we decided to exploit background modelling. We
      described the background intensities B(H-->) with an 11th degree polynomial in
      straight theta. This function predicts the local background b at each position H-
      > and defines the counting statistical distribution P(B), in which b serves as
      average and variance. The observation R defines P(R). This leads to P(I) =
      P(R)/P(B) and thus I = R - b and sigma(2)(I) = I so that the error sigma(I) is
      background independent. Within this framework we reanalysed the structure of the
      copper(II) derivative. Background modelling resulted in a structure model with an
      improved internal consistency. At the same time the unweighted R value based on
      all observations decreased from 10.6 to 8.4%. A redetermination of the structure
      at 120 K concluded the analysis.

PMID- 11468377
TI  - Two fluoradene derivatives: pseudosymmetry, eccentric ellipsoids and a phase
      transition.
AB  - Structures of two derivatives of the curved fluoradene ring system (C(19)H(12))
      have been determined. Both have phases that are highly pseudosymmetric. At room
      temperature crystals of 7b-triisopropylsilylfluoradene (C(28)H(32)Si) have a P1
      cell that contains two independent molecules (Z' = 2) and that is almost
      centered. Crystals of 7b-(2,4-dinitrophenyl)fluoradene (C(25)H(14)N(2)O(4)) have
      both a P2(1)/c cell with Z' = 1 and a P2(1)/c cell with Z' = 2. The molecular
      volumes in these two P2(1)/c structures differ by 0.7%, but the structures are
      otherwise virtually the same; the two independent molecules in the larger cell
      are related by a pseudotranslation. Some of the atomic ellipsoids in the P2(1)/c,
      Z' = 1 structure are very large and eccentric, and there are some hints in the
      diffraction pattern of an incipient phase transition, but the Z' = 1 and Z' = 2
      phases are clearly different. The P2(1)/c, Z' = 2 crystal at 295 K probably
      contains some volume fraction of the Z' = 1 phase; when the temperature is
      lowered to 273 K this fraction is decreased markedly. The pronounced
      pseudosymmetry in the P1 and P2(1)/c structures that have Z' = 2 has been
      investigated by analysing the atomic coordinates, by performing refinements in
      the smaller pseudocells and by making separate Wilson plots for the classes of
      reflections which are systematically strong and systematically weak. All three
      approaches are informative, but they reveal different information. Least-squares
      fits of coordinates of corresponding atoms measure the similarity of the
      molecular conformations. The Wilson plots allow a quantitative comparison of the
      intensities of the strong and weak reflections and thus an assessment of the
      deviations of the true structure from the smaller pseudocell structure.
      Comparison of the atomic displacements obtained in the full and pseudocell
      refinements shows where the structural distortions are largest and provides an
      indication of their directions.

PMID- 11468378
TI  - Correction of the space group of [Ni(bipy)(2)(ONO(2))(2)] x 2(pyrene).
AB  - The crystal structure of [Ni(bipy)(2)(ONO(2))(2)] x2(pyrene), poly[[[bis(nitrato
      O)nickel(II)]bis(mu-4,4'-bipyridyl-N,N'] bis(pyrene)], was originally reported in
      space group Pn [Biradha et al. (1999). Chem. Commun. pp. 1327--1328]. Reasons are
      given for changing the space group to P2(1)/n. Consequently, incorrect
      descriptions of the title compound in the literature must be altered. In
      particular, the structure is not polar. It is further contended that description
      in terms of 'complementary, interpenetrating covalent and noncovalent two
      dimensional networks' is misleading as the 'noncovalent network' (of pyrenes) has
      geometrical but not physical significance. The title compound is a typical host
      guest inclusion complex.

PMID- 11468379
TI  - Solid-state structures of group 1 and group 2 metal 1,5-naphthalenedisulfonates:
      systematic investigation of lamellar three-dimensional networks constructed by
      metal arenedisulfonate.
AB  - Seven Group 1 and Group 2 1,5-naphthalenedisulfonates (1,5-nds) have been
      synthesized and structurally characterized by single-crystal X-ray diffraction,
      IR spectroscopy and thermal gravimetric analysis. For Group 1 metal complexes,
      with M = Li(+) (1), Na(+) (2) and K(+) (3), all crystallize in the same space
      group (P2(1)/c) with the same composition, [M(2)(1,5-nds)(H(2)O)(2)]. They adopt
      similar three-dimensional packing arrangements with the metal-sulfonate inorganic
      layers pillared by naphthalene rings. However, the coordination behavior of three
      metal cations toward the SO(3)(-) group and water molecule are different,
      resulting in different architectures for the inorganic portion. For Group 2
      complexes with M = Mg(2+) (4), Ca(2+) (5), Sr(2+) (6) and Ba(2+) (7), Mg(2+)
      shows no direct coordination by the SO(3)(-) group while Ca(2+) is coordinated by
      four SO(3)(-) groups and a two-dimensional network is formed. Complexes (6) and
      (7) are isostructural, adopting the same three-dimensional, inorganic-organic
      pillared framework as seen for (1)-(3). The coordination behavior of the metal
      cations in these structures neatly illustrates the increase in coordination
      strength with decreasing charge/radius ratio for Group 1 and Group 2 metal
      cations with large organic anions.

PMID- 11468380
TI  - Structure determination of the [Fe(teec)(6)](BF(4))(2) metal complex from
      laboratory and synchrotron X-ray powder diffraction data with grid-search
      techniques.
AB  - The structure of the coordination compound [Fe(teec)(6)](BF(4))(2), hexa[1-(2
      chloroethyl)tetrazole]iron(II) di(borotetrafluoride), has been determined using
      the grid-search techniques of the program suite MRIA. A Guinier-camera data set
      was used to determine the unit cell, the space group and to position the initial
      model. A high-resolution synchrotron powder data set was used to position a more
      detailed model using torsion-angle variation and to refine the structure leading
      to Rp = 0.0689, Rw = 0.0805 and GoF = 1.38. The crystal structure at room
      temperature shows the existence of two symmetry-equivalent iron(II) ions in the
      high-spin state.

PMID- 11468381
TI  - Basic forms of supramolecular self-assembly organized by parallel and
      antiparallel hydrogen bonds in the racemic crystal structures of six
      disubstituted and trisubstituted cyclopentane derivatives.
AB  - A selection of stereoisomeric 2-hydroxy-1-cyclopentanecarboxamides, a 4-tert
      butyl derivative and three tert-butyl derivatives of the respective carboxylic
      acid were subjected to X-ray crystallography. The optically active molecules (I)-
      (VI) form racemic crystals. Each racemic structure is basically determined by two
      intermolecular hydrogen bonds of O--H...O==C--XH and O==C--X--H...OH types (X =
      O, NH). The partially similar patterns of close packing observed reflect five
      basic forms of supramolecular self-assembly. In the racemic crystals of chiral
      molecules, there are homo- and heterochiral chains of molecules formed by the
      principal (O--H...O==C) hydrogen bonds. These chains assemble either in a
      parallel or antiparallel mode. The parallel homochiral chains (hop) observed in
      structure (II), (1R*,2R*)-2-hydroxy-1-cyclopentanecarboxamide, demand the polar
      space group Pca2(1), while the parallel heterochiral chains (hep) are organized
      in antiparallel layers with space group P2(1)/n in structure (VI), (1R*,2S*,5R*-5
      tert-butyl-2-hydroxy-1-cyclopentanecarboxylic acid). Heterochiral chains in an
      antiparallel array (hea) are found in (I), (1R*,2S*)-2-hydroxy-1
      cyclopentanecarboxamide, and (V) [(1R*,2S*4S*)-4-tert-butyl-2-hydroxy-1
      cyclopentanecarboxylic acid, space group P2(1)/c]. Structures (IV), (1R*,2S*,4R*)
      4-tert-butyl-2-hydroxy-1-cyclopentanecarboxylic acid, and (III), (1R*,2R*,4S*)-4
      tert-butyl-2-hydroxy-1-cyclopentanecarboxamide, reveal that homochiral chains in
      an antiparallel array (hoa; cross-linked by heterochiral dimers held together by
      the second hydrogen bonds) can be formed by either translation (space group P1)
      or a screw axis (space group P2(1)/c). These alternatives are denoted hoa1 and
      hoa2. Similarly, within each pattern (hea, hep and hop) two slightly different
      alternatives can be expected. The partial similarities in the identified five
      patterns of hydrogen bonding are described by graph-set notations. Structures
      (I), (IV) and (V) can be characterized by a common supramolecular synthon, while
      the highest degree of similarity is shown by the isostructurality of (I) and (V).

PMID- 11468382
TI  - Direct observation of deuterium migration in crystalline-state reaction by single
      crystal neutron diffraction. III. Photoracemization of 1-cyanoethyl cobaloxime
      complexes.
AB  - The H atoms bonded to the chiral C atoms (stereogenic center) of the 1-cyanoethyl
      groups in two cobalt complexes, [(R)-1
      cyanoethyl]bis(dimethylglyoximato)(pyridine)cobalt(III) (2) and [(R,S)-1
      cyanoethyl]bis(dimethylglyoximato)(piperidine)cobalt(III) (3), were replaced with
      D atoms, such as Co--C*D(CH(3))CN. The crystals of the two cobalt complexes were
      irradiated with a xenon lamp for 72 h and 27 d, respectively. The unit-cell
      dimensions were gradually changed with retention of the single-crystal form. The
      crystal structures after irradiation were determined by neutron diffraction. In
      each crystal the chiral 1-cyanoethyl group of one of the two crystallographically
      independent molecules was partly inverted to the opposite configuration, whereas
      that of the other molecule kept the original configuration. The C*--D bond in the
      inverted group was completely conserved in the process of the inversion of the
      chiral alkyl group. This suggests that the inversion of the chiral 1-cyanoethyl
      group proceeds with the rotation of the cyanoethyl radical after the Co--C bond
      cleavage by photo-irradiation so that the opposite side of the radical faces the
      Co atom. This is followed by recombination of the Co--C bond to form the inverted
      1-cyanoethyl group.

PMID- 11468383
TI  - Crystal engineering in the gem-alkynol family: the key role of water in the
      structure of 2,3,5,6-tetrabromo-trans-1,4-diethynyl-cyclohexa-2,5-diene-1,4-diol
      dihydrate determined by X-ray and neutron diffraction at 150 K.
AB  - The structure of the title compound has been determined using low-temperature
      (150 K) single-crystal X-ray and neutron diffraction data. Crystals adopt the
      uncommon space group P4(2)/ncm and display a complex set of intermolecular
      interactions in which the water molecules play the crucial role: the water O-atom
      [O2(w)] accepts two hydrogen bonds and both water H atoms act as bifurcated
      donors. A set of O--H...O hydrogen bonds is formed around the 4(2) axis
      comprising (a) a cyclic tetrameric synthon involving four donor-H from two water
      molecules and two O(hydroxy) acceptors from two parent molecules, and (b) short
      discrete O(hydroxy)--H...O2(w) hydrogen bonds which link these tetramers along
      the c axis. Four Br...Br interactions [3.708 (1) A] form cyclic Br(4) tetramers
      around the 4 axis and are linked to the O--H...O system via O2(w)--H...Br bonds
      with H...Br = 2.995 (2) A. Finally, the O--H...O system is further linked to the
      parent molecules via C identical with C...H...O2(w) bonds of 2.354 (3) A. The
      supramolecular structure of the title hydrate is compared with that of the non
      hydrated parent molecule, which also forms cyclic O--H...O bonded tetrameric
      synthons, and with its (non-hydrated) tetrachloro analogue, which forms cyclic
      tetrameric Cl(4) synthons [Madhavi, Desiraju et al. (2000b). Acta Cryst. B56,
      1063--1070].

PMID- 11468384
TI  - Experimental and theoretical charge density of DL-alanyl-methionine.
AB  - X-ray diffraction data up to d = 0.50 A resolution have been collected at 100 K
      for a DL-alanyl-methionine single crystal using a CCD area detector. Multipolar
      crystallographic refinement was carried out and the electron density of the
      molecule has been analyzed. The deformation electron density around the S atom
      reveals two lone pairs with an sp(3) hybridization and agrees with the results of
      density functional theory calculations. The topological properties of the
      covalent bonds and of the hydrogen bonds have been investigated. Two weak polar
      intramolecular interactions of the type C(5) (pentagonal cyclic structure) have
      unfavorable geometrical parameters for hydrogen bonds and are devoid of critical
      points. The two electron lone pairs of the carbonyl oxygen appear asymmetric in
      the experimental deformation density. This could be attributed to the different
      strength of the hydrogen bond and intramolecular polar interaction involving the
      carbonyl oxygen. In the ab-initio-derived deformation maps, the asymmetry of the
      electron doublets is reproduced only very partially.

PMID- 11468385
TI  - Structural complexity of a polar perhydrotriphenylene inclusion compound brought
      to light by synchrotron radiation.
AB  - The complex diffraction pattern of the heavily disordered co-crystals of
      perhydrotriphenylene and 1-(4-nitrophenyl)piperazine (5C(18)H(30) x
      C(10)H(13)N(3)O(2)) has been investigated with synchrotron radiation and an area
      detector. Five (almost) complete, three-dimensional data sets have been obtained
      from the tips and the centre of a needle-like crystal at room temperature and 120
      K. They revealed a rich variety of features including one,- two- and three
      dimensional diffuse scattering, as well as incommensurate satellites. At the
      centre and one tip of the crystal the symmetry appears to be orthorhombic,
      whereas at the other tip the symmetry of the satellites and of some of the
      diffuse scattering is clearly monoclinic, indicating that the crystal is not
      homogeneous. Most of the scattering could be assigned to R/S occupational
      disorder of the chiral host molecules, to positional disorder of the guest
      molecules or to local distortions of the average structure. Assignments are based
      on the disorder deduced from the average structure and the molecular form factors
      of host and guest molecules which show characteristic patterns in reciprocal
      space. Two smaller, orthorhombic twin fragments and an additional phase with
      hexagonal symmetry have also been found.

PMID- 11468386
TI  - General rules for the packing of hydrogen-bonded crystals as derived from the
      analysis of squaric acid anions: aminoaromatic nitrogen base co-crystals.
AB  - Preparation and single-crystal X-ray structure determination of three co-crystals
      of hydrogen squarate, HSQ(-), with 2-aminopyrimidine, 3-aminopyridine and 4
      aminopyridine, and one of squarate, SQ(2-), with 8-aminoquinoline are reported.
      Their crystal packings are analyzed and discussed in terms of the intermolecular
      O--H...O, N--H...O/N and C--H...O hydrogen bonds formed. Although the fine
      details of the supramolecular architecture are barely rationalizable, the
      comparative analysis of the data makes it possible to suggest some simple rules
      that may be of general application for the packing of hydrogen-bonded crystals,
      i.e. Rule 1: 'All hydrogen-bond acceptors available in a molecule will be engaged
      in hydrogen bonding as far as there are available donors'; Rule 2: 'The hydrogen
      bond acceptors will be saturated in order of decreasing strength of the hydrogen
      bonds formed'.

PMID- 11468387
TI  - Ferroelectric--paraelectric phase transitions with no group--supergroup relation
      between the space groups of both phases?
AB  - The structures of Sr(3)(FeF(6))(2), beta-NbO(2), TlBO(2) and CrOF(3), previously
      reported as possible ferroelectrics with no group-supergroup relation between the
      ferroelectric and the paraelectric symmetries, have been carefully studied. We
      could not confirm any structural pseudosymmetry with respect to a space group
      which is not a supergroup of their room-temperature polar space group. In all
      cases, pseudosymmetry was indeed detected, but only for non-polar supergroups of
      the actual space groups of the structures. In this sense, the four compounds are
      possible ferroelectrics, but fulfilling the usual group-supergroup relation
      between the phase symmetries.

PMID- 11468388
TI  - Atomic force microscopy applications in macromolecular crystallography.
AB  - Atomic force microscopy (AFM) can be applied both in situ and ex situ to study
      the growth of crystals from solution. The method is particularly useful for
      investigating the crystallization of proteins, nucleic acids and viruses because
      it can be carried out in the mother liquor and in a non-perturbing fashion.
      Interactions and transformations between various growth mechanisms can be
      directly visualized as a function of supersaturation, as can the incorporation of
      diverse impurities and the formation and propagation of defects. Because the
      crystals can be observed over long periods, it is also possible to obtain precise
      quantitative measures of the kinetic parameters for nucleation and growth.
      Finally, AFM has allowed us to identify a number of previously unsuspected
      phenomena that influence nucleation, rate of growth and the ultimate perfection
      of macromolecular crystals. These are all features which are important in
      determining the ultimate resolution and quality of a crystal's diffraction
      pattern.

PMID- 11468389
TI  - Structure of rat transthyretin (rTTR) complex with thyroxine at 2.5 A resolution:
      first non-biased insight into thyroxine binding reveals different hormone
      orientation in two binding sites.
AB  - The first observation of the unique environment for thyroxine (T(4)) binding in
      tetrameric rat transthyretin (rTTR) is reported as determined by X-ray
      diffraction. These data revealed different modes of hormone binding in the two
      unique hormone-binding sites in the rat TTR tetramer channel. Differences in the
      orientation of thyroxine and the position of water molecules in the two binding
      sites further suggest a mechanism for the docking pathway of the hormone into the
      channel of TTR. Crystals of the rat transthyretin-thyroxine complex are
      isomorphous with those reported for apo rTTR and crystallized in the tetragonal
      space group P4(3)2(1)2 with four independent TTR monomeric subunits in the
      asymmetric part of the crystal lattice. Data were collected to 2.5 A resolution
      and the structure was refined to R = 20.9% for 15 384 data in the resolution
      range 12-2.5 A. Similar to human TTR, the rat protein is also a 54 000 Da
      tetramer with four identical polypeptide chains of 127 amino-acid residues. Of
      the 22 amino-acid residues which differ between the human and rat sequences, none
      are in the thyroxine-binding domains. Analysis of these structural data reveals
      that the tertiary structure is similar to that of hTTR, with only small
      differences in the flexible loop regions on the surface of the structure.
      Conformational changes of the amino acids in the channel result in a hydrogen
      bonded network that connects the two binding domains, in contrast to the hydrogen
      bonds formed along the tetramer interface in the apo transthyretin structure.
      These changes suggest a mechanism for the signal transmission between thyroxine
      binding domains.

PMID- 11468390
TI  - The structure of leech anti-platelet protein, an inhibitor of haemostasis.
AB  - Leech anti-platelet protein (LAPP) from the leech Haementeria officinalis is a
      collagen-binding protein that inhibits the collagen-mediated adhesion of blood
      platelets. The crystal structure of recombinant LAPP has been determined using
      single isomorphous replacement with anomalous scattering combined with solvent
      flattening and threefold molecular averaging. The model of LAPP has been refined
      to 2.2 A resolution (R factor 21.5%; free R factor 24.0%). LAPP contains an 89
      residue C-terminal domain consisting of a central six-stranded antiparallel beta
      sheet flanked on one side by an alpha-helix and on the other side by two extended
      loops with little secondary structure. A 36-residue N-terminal region is not
      visible in the electron-density map. This region is rich in glycine and lacks
      hydrophobic residues. It probably does not have a compact globular fold, but
      instead has an extended conformation and is flexible. The crystal packing
      suggests that LAPP may form tightly interacting dimers. The fold of the C
      terminal domain of LAPP closely resembles that of the N-domain of hepatocyte
      growth factor (HGF), which classifies LAPP as a PAN domain. However, no
      significant sequence homology exists between LAPP and other PAN domains. Common
      structural features between LAPP and the HGF N-domain include two disulfide bonds
      that link the alpha-helix to the central region of the protein and five residues
      with a conserved hydrophobic nature that are located in the core of the domain.
      These conserved structural features may be an important determinant of the PAN
      domain type of fold.

PMID- 11468391
TI  - Structure of Haemophilus influenzae HslU protein in crystals with one-dimensional
      disorder twinning.
AB  - The structure of the Haemophilus influenzae HslU protein, a molecular chaperone
      of the Clp/Hsp100 family, has been solved to 2.3 A by molecular replacement using
      a model of the homologous Escherichia coli protein. The crystals in which the
      structure was solved have an unusual twinning, or one-dimensional disorder, in
      which each successive crystal-packing layer is displaced laterally relative to
      the one below it. A model for the twinning and an algorithm for detwinning the
      data are described. It is known from other work that when the HslU hexamer binds
      its cognate protease HslV, the carboxy-terminal helices of HslU protomers distend
      and bind between HslV subunits. Comparison of HslU alone with its structure in
      the HslUV complex reveals several conserved amino-acid residues whose side-chain
      interactions differ between the two structures, suggesting that they may be part
      of a conformational switch that facilitates the release of the HslU carboxy
      terminal helices when HslV binds.

PMID- 11468392
TI  - Phase changes in T(3)R(3)(f) human insulin: temperature or pressure induced?
AB  - The structure of T(3)R(3) hexameric human insulin has been determined at 100 K
      from two different crystals at 1.2 and 1.3 A resolution and refined to residuals
      of 0.169 and 0.176, respectively. Owing to a phase change, the c axis is double
      its room-temperature value and the asymmetric unit contains two independent TR(f)
      insulin dimers. Compared with the orientation in the room-temperature structure,
      one dimer undergoes a rotation about the c axis of -5 degrees, while the second
      is rotated +4 degrees. A superposition of the backbone atoms of the two
      independent dimers shows that the C(alpha) atoms of five residues within the R(f)
      state monomers are displaced by more than 1.0 A; smaller displacements are
      observed for the T-state monomers. Four zinc ions lie on the crystallographic
      threefold axis and each forms bonds to three symmetry-related HisB10
      N(varepsilon2) atoms from the T- and R(f)-state trimers. While three of the zinc
      ions are tetrahedrally coordinated with a chloride ion completing the
      coordination sphere, mixed tetrahedral/octahedral coordination is observed for
      one of the T-state zinc ions. The three symmetry-related "phenolic binding sites"
      in one hexamer contain water molecules and a glycerol molecule, but the same
      sites in the second hexamer are occupied by a zinc ion coordinated to an
      alternate conformation of HisB10, a symmetry-related HisB5 and two chloride ions.
      Two additional and partially occupied zinc ion sites are observed at the
      interface between the two independent dimers. One zinc ion is coordinated by a T
      state HisB5 of one dimer, an R-state HisB5 of the second dimer and two water
      molecules; the second zinc ion is coordinated by an alternate side-chain
      conformation of the T-state HisB5 and three water molecules. The carboxyl group
      of one GluB13 side chain, which exists in two discrete conformations, appears to
      be protonated, because short contacts exist to a second carboxyl group or to a
      carbonyl O atom.

PMID- 11468393
TI  - Structure of the insecticidal bacterial delta-endotoxin Cry3Bb1 of Bacillus
      thuringiensis.
AB  - The coleopteran-active delta-endotoxin Cry3Bb1 from Bacillus thuringiensis (Bt)
      strain EG7231 is uniquely toxic to Diabrotica undecimpunctata, the Southern corn
      rootworm, while retaining activity against Leptinotarsa decemlineata, the
      Colorado potato beetle. The crystal structure of the delta-endotoxin Cry3Bb1 has
      been refined using data collected to 2.4 A resolution, with a residual R factor
      of 17.5% and an R(free) of 25.3%. The structure is made up of three domains: I, a
      seven-helix bundle (residues 64-294); II, a three-sheet domain (residues 295
      502); and III, a beta-sandwich domain (residues 503-652). The monomers in the
      orthorhombic C222(1) crystal lattice form a dimeric quaternary structure across a
      crystallographic twofold axis, with a channel formed involving interactions
      between domains I and III. There are 23 hydrogen bonds between the two monomers
      conferring structural stability on the dimer. It has been demonstrated that
      Cry3Bb1 and the similar toxin Cry3A form oligomers in solution. The structural
      results presented here indicate that the interactions between domains I and III
      could be responsible for the initial higher order structure and have implications
      for the biological activity of these toxins. There are seven additional single
      amino-acid residues in the sequence of Cry3Bb1 compared with that of Cry3A; one
      in domain I, two in domain II and four in domain III, which also shows the
      largest conformational difference between the two proteins. These changes can be
      implicated in the selectivity differences noted for these two delta-endotoxins.

PMID- 11468394
TI  - X-ray structure of a blue copper nitrite reductase at high pH and in copper-free
      form at 1.9 A resolution.
AB  - Copper-containing nitrite reductases possess a trimeric structure where the
      catalytic Cu site, located at the monomer-monomer interface, resembles the
      catalytic sites of a number of Zn enzymes. Nitrite reductase from Alcaligenes
      xylosoxidans has optimum activity at pH 5.2 which decreases to a negligible level
      at pH 8. The structure of this nitrite reductase has previously been determined
      at pH 4.6. It has now been crystallized under new conditions at pH 8.5. Its
      crystallographic structure provides a structural explanation for the greatly
      reduced activity of the enzyme at high pH. Characterization of overexpressed
      protein in solution by EXAFS suggested that the protein lacked Cu in the
      catalytic type 2 Cu site and that the site was most probably occupied by Zn.
      Using the anomalous signals from Cu and Zn, the crystal structure revealed that
      the expressed protein was devoid of Cu in the catalytic site and that only a
      trace amount (<10%) of Zn was present at this site in the crystal. Despite the
      close structural similarity of the catalytic site to a number of Zn enzymes,
      these data suggest that Zn, if it binds at the catalytic copper site, binds
      weakly in nitrite reductase.

PMID- 11468395
TI  - Structure of tetragonal hen egg-white lysozyme at 0.94 A from crystals grown by
      the counter-diffusion method.
AB  - Very high quality crystals of tetragonal hen egg-white lysozyme were grown in the
      Advanced Protein Crystallization Facility (APCF) on board the Space Shuttle using
      a modified free-interface diffusion (FID) reactor designed ad hoc to have a
      longer diffusion path. This design allows the performance of true counter
      diffusion experiments. Crystals were obtained under the classical chemical
      conditions defined 50 y ago with NaCl as a crystallizing agent and acetate pH 4.5
      as a buffer. Counter-diffusion crystallization allows a "physical" instead of
      chemical optimization of growth conditions: indeed, this method screens for the
      best supersaturation conditions in a single trial and yields crystals of very
      high quality. A complete diffraction data set was collected at atomic resolution
      from one of these crystals using synchrotron radiation at the DESY-EMBL
      beamlines. The overall R(merge) on intensities in the resolution range 31-0.94 A
      was 5.2% and the data were 98.9% complete. Refinement was carried out with the
      programs CNS and SHELX97 to a final crystallographic R factor of 12.26% for 72
      390 reflections. A mean standard uncertainty in the atomic positions of 0.024 A
      was estimated from inversion of blocked least-squares matrices. 22 side chains
      show alternate conformations and the loop 59-75 adopts in the same crystal
      packing two conformations that were observed for either triclinic or tetragonal
      lysozyme in previous high-resolution studies. In addition to 255 water molecules,
      the crystallizing agent (one hexacoordinated sodium ion and five chloride anions)
      participates in the ordered lysozyme hydration shell.

PMID- 11468396
TI  - COMO: a program for combined molecular replacement.
AB  - The combined molecular-replacement protocol uses a limited six-dimensional search
      to solve a structure by the molecular-replacement method, with the sampling of
      the rotational degrees of freedom guided by the rotation function. This protocol
      therefore automatically combines the information on the rotational and
      translational parameters of the search model. The combined molecular-replacement
      protocol has been implemented in a new computer program, COMO. The calculation of
      the Patterson correlation translation function has been optimized to improve its
      speed performance. A packing check is implemented that automatically removes
      impossible solutions and thereby increases the signal in the calculation. A
      family of atomic models can be used as the search model; the program will
      automatically select the model that gives the best result. The command interface
      is well organized and requires the definition of only a few critical parameters
      by the user. In addition, a graphical user interface has been constructed for the
      program. The program has been used to solve several difficult molecular
      replacement problems. A case is presented where the program automatically
      determined the orientation and position of five copies of a search model in a
      high-symmetry space group.

PMID- 11468397
TI  - Crystallization and preliminary X-ray analysis of jararhagin, a
      metalloproteinase/disintegrin from Bothrops jararaca snake venom.
AB  - Jararhagin is a toxic protein, isolated from the venom of the snake Bothrops
      jararaca, which is composed of a metalloprotease domain coupled to a
      disintegrin/cysteine-rich domain. It induces local haemorrhage owing to the
      proteolytic digestion of the basement membrane of capillaries. Jararhagin also
      cleaves the alpha(2)beta(1) integrin on the surface of platelets, thereby acting
      as a potent inhibitor of collagen-induced platelet aggregation. Crystals of
      jararhagin were obtained by the vapour-diffusion technique at 273 K in 200 mM
      sodium acetate, 100 mM cacodylate buffer pH 6.5 and 30% PEG 8000. Diffraction
      data have been obtained to a resolution of 2.8 A from a single frozen crystal,
      which belonged to space group P2(1)2(1)2(1) with unit-cell parameters a = 73.7, b
      = 100.3, c = 133.4 A. The asymmetric unit contains two jararhagin molecules and
      has a solvent content of 45%. A molecular-replacement solution has been obtained
      using a homology-built model based on the crystal structure of acutolysin, a
      haemorrhagic zinc metalloproteinase from the venom of the snake Agkistrodon
      acutus; attempts are under way to locate the remaining domains.

PMID- 11468398
TI  - Cloning, purification and characterization of the 6-phospho-3-hexulose isomerase
      YckF from Bacillus subtilis.
AB  - The enzyme 6-phospho-3-hexulose isomerase (YckF) from Bacillus subtilis has been
      prepared and crystallized in a form suitable for X-ray crystallographic analysis.
      Crystals were grown by the hanging-drop method at 291 K using polyethylene glycol
      2000 monomethylether as precipitant. They diffract beyond 1.7 A using an in-house
      Cu Kalpha source and belong to either space group P6(5)22 or P6(1)22, with unit
      cell parameters a = b = 72.4, c = 241.2 A, and have two molecules of YckF in the
      asymmetric unit.

PMID- 11468399
TI  - Characterization of a novel pectate lyase, Pel10A, from Pseudomonas cellulosa.
AB  - Biological recycling of plant material is essential for biosphere maintenance.
      This perpetual task involves a complex array of enzymes, including extracellular
      polysaccharide hydrolases and lyases. Whilst much is known about the structure
      and function of the hydrolases, relatively little is known about the structures
      and mechanisms of the corresponding lyases. To this end, crystals of the
      catalytic module of a novel family 10 pectate lyase, Pel10A from Pseudomonas
      cellulosa, were obtained using polyethylene glycol 2000 monomethylether as a
      precipitant. They belong to space group P2(1), with unit-cell parameters a =
      47.7, b = 106.1, c = 55.4 A, beta = 92.0 degrees, and have two molecules in the
      asymmetric unit. The crystals diffract beyond 1.5 A using synchrotron radiation.

PMID- 11468400
TI  - Liganded and unliganded forms of Antarctic fish haemoglobins in polyethylene
      glycol: crystallization of an R-state haemichrome intermediate.
AB  - Liganded and unliganded forms of two Antarctic fish haemoglobins, from Trematomus
      newnesi and T. bernacchii, have been crystallized in low-salt media using
      polyethylene glycol as precipitant. In particular, crystals of air-exposed T.
      newnesi carbomonoxy haemoglobin were found to be isomorphous to the crystals
      grown in high-salt media. Preliminary X-ray analysis of the diffraction data
      revealed that the beta-haem iron of this haemoglobin is in the haemichrome state,
      with both the proximal and distal histidyl residues linked to the iron. This is
      the first crystallization of a haemichrome intermediate of a vertebrate
      haemoglobin.

PMID- 11468401
TI  - Crystallization and preliminary X-ray crystallographic analysis of deoxyuridine
      triphosphate nucleotidohydrolase from Saccharomyces cerevisiae.
AB  - Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) from Saccharomyces
      cerevisiae is essential for cell viability. It has been overexpressed in
      Escherichia coli and has been crystallized at 296 K using polyethylene glycol
      (PEG) 1500 as a precipitant. The crystals belong to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 59.48, b = 138.54, c = 157.91 A,
      alpha = beta = gamma = 90 degrees. Two molecules of trimeric dUTPase from S.
      cerevisiae are present in the asymmetric unit, giving a crystal volume per
      protein mass (V(M)) of 3.36 A(3) Da(-1) and a solvent content of 63%. The
      diffraction limit of the crystals could be significantly extended by the crystal
      annealing procedure. A set of native data extending to 2.7 A resolution has been
      collected at 100 K using synchrotron X-rays.

PMID- 11468402
TI  - Crystals of a mutant form of ribosomal protein L22 rendering bacterial ribosomes
      resistant to erythromycin.
AB  - A mutant form of Thermus thermophilus ribosomal protein L22 responsible for
      erythromycin resistance has been overexpressed in Escherichia coli, purified to
      homogeneity and crystallized using the hanging-drop vapour-diffusion technique.
      While several different crystallization conditions were found, only one set of
      conditions yielded crystals suitable for X-ray diffraction analysis. These
      crystals grow as thick plates, with unit-cell parameters a = 31.8, b = 86.59, c =
      38.96 A, beta = 104.47 degrees. The crystals belong to the space group P2(1) and
      diffract to 1.8 A resolution. On the basis of density calculations, two monomers
      are predicted per asymmetric unit (V(M) = 2.06 A(3) Da(-1)), with a solvent
      content of 40%.

PMID- 11468403
TI  - Preparation and crystallization of the stimulatory and inhibitory complexes of
      GTP cyclohydrolase I and its feedback regulatory protein GFRP.
AB  - Mammalian GTP cyclohydrolase I is a decameric enzyme in the first and rate
      limiting step in the biosynthesis of tetrahydrobiopterin, which is an essential
      cofactor for enzymes producing neurotransmitters such as catecholamines and for
      nitric oxide synthases. The enzyme is dually regulated by its feedback regulatory
      protein GFRP in the presence of its stimulatory effector phenylalanine and its
      inhibitory effector biopterin. Here, both the stimulatory and inhibitory
      complexes of rat GTP cyclohydrolase I bound to GFRP were crystallized by vapour
      diffusion. Diffraction data sets at resolutions of 3.0 and 2.64 A were collected
      for the stimulatory and inhibitory complexes, respectively. Each complex consists
      of two GTPCHI pentamer rings and two GFRP pentamer rings, with pseudo-52 point
      group symmetry.

PMID- 11468404
TI  - Crystallization and preliminary X-ray analysis of catalase-peroxidase from the
      halophilic archaeon Haloarcula marismortui.
AB  - Catalase-peroxidases are bifunctional enzymes found in many microorganisms.
      Crystals of catalase-peroxidase from the halophilic archaeon Haloarcula
      marismortui were obtained using the hanging-drop vapour-diffusion method. The
      rhombic plate-shaped crystals were grown from purified protein solution using
      (NH(4))(2)SO(4) as precipitant at 293 K. The crystal belongs to the monoclinic
      system, space group C2, and diffracted beyond 2.0 A resolution.

PMID- 11468405
TI  - Crystallization and preliminary X-ray crystallographic studies of recombinant
      thermoresistant gluconate kinase GntK from Escherichia coli.
AB  - The thermoresistant gluconate kinase GntK from Escherichia coli, an essential
      enzyme in gluconate metabolism, has been expressed, purified and crystallized.
      For crystallization, the hanging-drop vapour-diffusion method was used with
      polyethylene glycol (PEG) 6000 and lithium chloride as precipitants. Three
      crystal forms belonging to the monoclinic space group C2 or the orthorhombic
      space groups P2(1)2(1)2(1) and P2(1)2(1)2 were obtained. The unit-cell parameters
      are a = 75.0, b = 79.3, c = 70.2 A, beta = 105.3 degrees (C2), a = 52.0, b =
      79.3, c = 89.8 A (P2(1)2(1)2(1)) and a = 70.1, b = 74.1, c = 78.9 A (P2(1)2(1)2).
      In all three crystal forms, there are two molecules in the asymmetric unit; the
      different forms occur in the same crystallization drop. The crystals diffract to
      at least 2.0 A using synchrotron radiation.

PMID- 11468406
TI  - Crystallization and preliminary crystallographic studies of an apoptosis-linked
      calcium-binding protein ALG-2.
AB  - ALG-2 is an apoptosis-linked Ca(2+)-binding protein. It is required for T-cell
      receptor-induced, Fas-induced and glucocorticoid-induced cell death.
      Structurally, ALG-2 contains five putative EF-hand Ca(2+)-binding sites. Ca(2+)
      free ALG-2 was crystallized in two crystal forms by the hanging-drop vapour
      diffusion method.

PMID- 11468407
TI  - Expression, refolding and crystallization of the OpcA invasin from Neisseria
      meningitidis.
AB  - OpcA is an integral outer membrane from the Gram-negative pathogen Neisseria
      meningitidis that plays a role in adhesion of meningococci to host cells. The
      protein was overexpressed in Escherichia coli in an insoluble form and a
      procedure developed for refolding by rapid dilution from denaturant into
      detergent solution. The refolded material was identical to native OpcA isolated
      from meningococci, as judged by overall molecular weight, migration on SDS-PAGE
      and reaction against monoclonal antibodies. Both native and recombinant OpcA
      crystallized under similar conditions to give an orthorhombic crystal form
      (P2(1)2(1)2), with unit-cell parameters a = 96.9, b = 46.3, c = 74.0 A. Complete
      data sets of reflections were collected from native and refolded OpcA to 2.0 A
      resolution.

PMID- 11468408
TI  - Coexpression, copurification, crystallization and preliminary X-ray analysis of a
      complex of ARL2-GTP and PDE delta.
AB  - The small GTPase ARL2 (from Mus musculus) and an effector protein, the delta
      subunit of human cGMP phosphodiesterase (hPDE delta), were coexpressed and
      copurified from Escherichia coli as a stable complex. Coexpression significantly
      increased the otherwise low yield of PDE delta production in E. coli. The
      complex, which contains ARL2 in the activated GTP-bound form, was crystallized in
      two forms. The first belongs to the monoclinic space group P2(1), with unit-cell
      parameters a = 48.1, b = 45.7, c = 74.7 A, beta = 94.0 degrees and one complex
      (39 kDa) in the asymmetric unit. Cryocooled crystals diffract to 2.3 A using
      synchrotron radiation. The micro-focused X-ray beam at beamline ID13 (ESRF)
      allowed the use of very small crystals, which helped to overcome twinning and
      enabled the identification of a molecular-replacement solution. The second form
      recrystallized from the first one after several months. These crystals belong to
      the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 44.5, b
      = 65.4, c = 104.4 A and one complex in the asymmetric unit. They diffracted to
      1.8 A using synchrotron radiation.

PMID- 11468409
TI  - Crystallization and preliminary X-ray study of endopolygalacturonase from the
      pathogenic fungus Stereum purpureum.
AB  - Crystals of endopolygalacturonase I from Stereum purpureum have been obtained by
      the vapour-diffusion method. Prior to crystallization work, endopolygalacturonase
      I was deglycosylated with endo-beta-N-acetylglucosaminidase H. The crystal
      diffracts to ultrahigh (0.96 A) resolution using synchrotron radiation and
      belongs to space group P1, with unit-cell parameters a = 37.26, b = 46.34, c =
      52.05 A, alpha = 67.17, beta = 72.44, gamma = 68.90 degrees.

PMID- 11468410
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      analysis of the human calcium-binding protein MRP14 (S100A9).
AB  - MRP14 is a protein that is specifically expressed in myeloid and epithelial cells
      during the stages of acute or chronic inflammatory states such as rheumatoid
      arthritis or sarcoidosis. MRP14 has EF-hand motifs as Ca(2+)-binding sites and
      belongs to the S100 family of proteins. This paper deals with the sample
      preparation (cloning, overexpression and purification), crystallization and
      preliminary crystallographic analysis of recombinant human MRP14. Crystals of
      MRP14 were obtained by the hanging-drop vapour-diffusion method. MRP14 crystals
      belong to space group P2(1), with unit-cell parameters a = 57.59, b = 178.44, c =
      61.23 A, beta = 113.17 degrees, and diffract to 2.1 A resolution.

PMID- 11468411
TI  - Crystallization and preliminary X-ray diffraction data of the second and
      archaebacterial-type aspartyl-tRNA synthetase from Thermus thermophilus.
AB  - The archaebacterial-type aspartyl-tRNA synthetase (AspRS2) from the thermophilic
      eubacterium Thermus thermophilus was crystallized using the hanging-drop vapour
      diffusion method. Crystals grew at pH 9.5 in the presence of PEG 8000 and NaCl. A
      native diffraction data set has been collected at 2.5 A resolution using
      synchrotron radiation and cryocooling. Crystals belong to the orthorhombic space
      group P2(1)2(1)2(1), with unit-cell parameters a = 57.3, b = 121.9, c = 166.9 A
      and V(M) = 3.03 A(3) Da(-1). There is one dimer of M(r) 96 000 per asymmetric
      unit. A molecular-replacement analysis gave solutions for the rotation and
      translation functions.

PMID- 11468412
TI  - Purification, crystallization and identification by X-ray analysis of a prostate
      kallikrein from horse seminal plasma.
AB  - The purification, crystallization and identification by X-ray diffraction
      analysis of a horse kallikrein is reported. The protein was purified from horse
      seminal plasma. Crystals belong to space group C2 and the structure was solved by
      the MIRAS method, with two heavy-atom derivatives of mercury and platinum. X-ray
      diffraction data to 1.42 A resolution were collected at the ESRF synchrotron
      radiation source.

PMID- 11468413
TI  - Crystallization and preliminary X-ray analysis of clade I catalases from
      Pseudomonas syringae and Listeria seeligeri.
AB  - Haem-containing catalases are homotetrameric molecules that degrade hydrogen
      peroxide. Phylogenetically, the haem-containing catalases can be grouped into
      three main lines or clades. The crystal structures of seven catalases have been
      determined, all from clades II and III. In order to obtain a structure of an
      enzyme from clade I, which includes all plant, algae and some bacterial enzymes,
      two bacterial catalases, CatF from Pseudomonas syringae and Kat from Listeria
      seeligeri, have been crystallized by the hanging-drop vapour-diffusion technique,
      using PEG and ammonium sulfate as precipitants, respectively. Crystals of P.
      syringae CatF, with a plate-like morphology, belong to the monoclinic space group
      P2(1), with unit-cell parameters a = 60.6, b = 153.9, c = 109.2 A, beta = 102.8
      degrees. From these crystals a diffraction data set to 1.8 A resolution with 98%
      completeness was collected using synchrotron radiation. Crystals of L. seeligeri
      Kat, with a well developed bipyramidal morphology, belong to space group I222 (or
      I2(1)2(1)2(1)), with unit-cell parameters a = 74.4, b = 121.3, c = 368.5 A. These
      crystals diffracted beyond 2.2 A resolution when using synchrotron radiation, but
      presented anisotropic diffraction, with the weakest direction perpendicular to
      the long c axis.

PMID- 11468414
TI  - Crystallization and preliminary X-ray diffraction studies on the N-utilizing
      substance A (NusA) from Mycobacterium tuberculosis.
AB  - N-utilizing substance A (NusA) is a protein which performs several roles as a
      cofactor of DNA-dependent RNA polymerase. Its acts as an elongation factor and
      facilitates pausing, termination and the formation of a complex assembly that
      mediates transcription antitermination in eubacteria. Biochemical and biophysical
      data in the literature suggest that this protein performs these functions by
      binding to the core RNA polymerase, other protein factors and certain RNA
      fragments having specific signal sequences. The NusA of Mycobacterium
      tuberculosis has been cloned and overexpressed in Escherichia coli and
      crystallized using the hanging-drop vapour-diffusion method. The space group is
      P3(1)21, with unit-cell parameters a = b = 78.1, c = 180.3 A. A native data set
      complete to 1.7 A resolution has been collected from a single crystal.

PMID- 11468415
TI  - Crystallization and preliminary X-ray diffraction studies of recombinant
      Escherichia coli 4-diphosphocytidyl-2-C-methyl-D-erythritol synthetase.
AB  - Diphosphocytidyl-methylerythritol (DPCME) synthetase is involved in the
      mevalonate-independent pathway of isoprenoid biosynthesis, where it catalyses the
      formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from 2-C-methyl-D
      erythritol 4-phosphate and CTP. The Escherichia coli enzyme has been cloned,
      expressed in high yield, purified and crystallized. Elongated tetragonal
      prismatic crystals grown by the hanging-drop vapour-diffusion method using
      polyethylene glycol (PEG) 4000 as the precipitant belong to space group
      P4(1)2(1)2 (or P4(3)2(1)2), with unit-cell parameters a = b = 73.60, c = 175.56
      A. Diffraction data have been recorded to 2.4 A resolution using synchrotron
      radiation.

PMID- 11468416
TI  - The preparation and crystallization of Fab fragments of a family of mouse
      esterolytic catalytic antibodies and their complexes with a transition-state
      analogue.
AB  - The Fab fragments of a family of mouse esterolytic monoclonal antibodies MS6-12,
      MS6-126 and MS6-164 have been obtained by digestion of whole antibodies with
      papain, purified and crystallized in a range of different forms either alone or
      in complex with a transition-state analogue. The crystals diffract X-rays to
      resolutions between 2.1 and 1.2 A and are suitable for structural studies. The
      determination of these structures could be important in understanding the
      different catalytic power of each of these related catalytic antibodies.

PMID- 11468417
TI  - Molray--a web interface between O and the POV-Ray ray tracer.
AB  - A publicly available web-based interface is presented for producing high-quality
      ray-traced images and movies from the molecular-modelling program O [Jones et al.
      (1991), Acta Cryst. A47, 110-119]. The interface allows the user to select O-plot
      files and set parameters to create standard input files for the popular ray
      tracing renderer POV-Ray, which can then produce publication-quality still images
      or simple movies. To ensure ease of use, we have made this service available to
      the O user community via the World Wide Web. The public Molray server is
      available at http://xray.bmc.uu.se/molray.

PMID- 11468418
TI  - A test of macromolecular crystallization in microgravity: large well ordered
      insulin crystals.
AB  - Crystals of insulin grown in microgravity on Space Shuttle Mission STS-95 were
      extremely well ordered and unusually large (many >2 mm). The physical
      characteristics of six microgravity and six earth-grown crystals were examined by
      X-ray analysis employing superfine phi slicing and unfocused synchrotron
      radiation. This experimental setup allowed hundreds of reflections to be
      precisely examined from each crystal in a short period of time. The microgravity
      crystals were on average 34 times larger, had sevenfold lower mosaicity, had 54
      fold higher reflection peak heights and diffracted to significantly higher
      resolution than their earth-grown counterparts. A single mosaic domain model
      could account for the observed reflection profiles in microgravity crystals,
      whereas data from earth crystals required a model with multiple mosaic domains.
      This statistically significant and unbiased characterization indicates that the
      microgravity environment was useful for the improvement of crystal growth and the
      resultant diffraction quality in insulin crystals and may be similarly useful for
      macromolecular crystals in general.

PMID- 11468419
TI  - HIV-protease inhibitors contribute to P-glycoprotein efflux function defect in
      peripheral blood lymphocytes from HIV-positive patients receiving HAART.
AB  - P-glycoprotein (P-gp) has been found expressed in normal human cells, such as
      bone marrow and peripheral blood cells. The aim of this study was to investigate
      whether HIV-protease inhibitors (HIV-PIs) interact with P-gp efflux function in
      normal human peripheral blood lymphocytes (PBLs) and CD34+ progenitor cells.
      Moreover, we analyzed the in vivo effect of HIV-PIs on P-gp function in PBLs from
      HIV-infected patients receiving highly active antiretroviral therapy (HAART). We
      found that HIV-PIs (i.e., ritonavir, saquinavir, nelfinavir and indinavir)
      interfere with P-gp function in normal PBLs as demonstrated by the reduced efflux
      of rhodamine 123 (Rh123). This effect was dose-dependent and suggested the
      following hierarchy: ritonavir > saquinavir > nelfinavir > indinavir. We further
      analyzed the effect of HIV-PIs on the P-gp function in specific PBLs subsets. Our
      results show an HIV-PI-induced inhibition of P-gp function in CD4+ and CD8+ T
      cell subsets, mostly caused by the effect on the naive compartment of both CD4+
      and CD8+ T cells. The same inhibitory effect was found in CD34+ hematopoietic
      progenitor cells. With respect to the in vivo evaluation of P-gp function in PBLs
      from HIV-infected patients, we found reduced levels of Rh123 efflux that reached
      the lowest value in AIDS patients receiving HAART. We concluded that HIV-PIs
      interfere with P-gp function in major cellular targets for HIV infection, such as
      CD4+ T cells and CD34+ progenitor cells. This ability may contribute to P-gp
      efflux function defect found in HIV-infected patients and suggests that drug
      interaction studies are crucial to an overall understanding of the effects of
      this important group of drugs.

PMID- 11468420
TI  - Comparison of different treatment regimens for the emergence of new resistance
      under therapy.
AB  - OBJECTIVE: To compare the effects of different therapy regimens on the
      probability of emergence of new resistant mutants during therapy. METHODS: We
      developed a stochastic model of infection and treatment to calculate the
      probability of de novo resistance during therapy. We simulated diverse treatment
      regimens, with different efficacy in controlling HIV replication. We studied the
      use of genotypic testing to choose treatment protocols specifically tailored
      against the wild type. RESULTS: The probability of emergence of a previously
      nonexisting drug-resistant mutant during therapy depends crucially on the drug
      regimen used. In particular, therapy protocols targeting the wild-type strain may
      lead to a higher probability of treatment failure due to resistance. Conversely,
      targeting the minority strains in the population, which readily mutate into the
      resistant variety, significantly lowers the probability of a new resistant
      emerging under therapy. CONCLUSIONS: Use of genotypic testing may lead to wrong
      decisions in the choice of therapy if the population dynamics of production of
      new resistant mutants is not taken into account.

PMID- 11468421
TI  - Preliminary data of a prospective study on neuropsychiatric side effects after
      initiation of efavirenz.
AB  - OBJECTIVE: To assess baseline variables able to predict neuropsychiatric side
      effects (NPSEs) associated with the initiation of an efavirenz (EFV)-containing
      regimen in HIV-1-infected patients. DESIGN: Open-label, prospective,
      observational study. METHODS: Consecutive HIV-1-infected outpatients in whom EFV
      was prescribed underwent a psychiatric interview. At baseline and at 2, 4, and 12
      weeks, patients completed the Symptoms Check List-90-Revised (SCL-90-R), the
      Medical Outcome Study for HIV-positive patients (MOS-HIV), and a standardized
      questionnaire concerning potential NPSEs. RESULTS: Preliminary data showed that
      discontinuation of EFV because of NPSEs occurred in 4 of 31 patients (13%).
      Patients who completed the follow-up showed a decrease in SCL-90-R total score (p
      =.004) and in several subscales such as Interpersonal Sensitivity (p =.009),
      Depression (p =.001), and Anxiety (p =.040), whereas no changes in MOS-HIV were
      observed. Having fewer years of education (p =.006), having fewer baseline
      central nervous symptoms (p =.000), reporting better baseline physical status (p
      =.013), and having higher baseline scores in the Heath Transition subscale of the
      MOS-HIV (p =.000) and in the Somatization subscale of the SCL-90-R (p =.002) were
      associated with more NPSEs. CONCLUSION: Patients maintained on EFV showed a
      decrease in psychologic distress related to self-image, depression, and anxiety,
      without any effect on quality of life. Patients with a lower level of education,
      those who feel physically and psychologically better at baseline than in the
      past, and those who suffer from more distress as a result of physical complaints
      may be at greater risk of reporting more NPSEs after EFV initiation.

PMID- 11468422
TI  - Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir
      in HIV-1-infected individuals.
AB  - OBJECTIVE: To compare the steady state plasma pharmacokinetics of 1000 mg of
      saquinavir (SQV) in a soft-gel capsule (SGC) formulation in combination with 100
      mg of ritonavir (RTV) (capsules) in a twice-daily dosing regimen in HIV-1
      infected individuals with historical controls who used 400 mg of SQV in a hard
      gel capsule (HGC) formulation in combination with 400 mg of RTV and to
      investigate the plasma pharmacokinetics of the 1000 mg/100 mg regimen after
      normal and high-fat breakfasts. DESIGN: Open-label, crossover, steady-state
      pharmacokinetic study. METHODS: Six HIV-1-infected individuals who used either
      1200 mg of SQV (SGC or HGC) three times daily or 400 mg twice daily in
      combination with 400 mg of RTV twice daily were included. Each patient was
      switched to 1000 mg of SQV SGC twice daily in combination with 100 mg of RTV
      twice daily. After 14 days, the patients came to the hospital for assessment of a
      pharmacokinetic profile during 12 hours. Patients were randomized to receive a
      high-fat (+/-45 g of fat) or normal (+/-20 g of fat) breakfast. After 7 days, a
      second pharmacokinetic profile was assessed after ingestion of the drugs with the
      alternate breakfast. A noncompartmental pharmacokinetic method was used to
      calculate the area under the plasma concentration versus time curve (AUC0-12h),
      the maximum plasma concentration (Cmax), the plasma trough concentration (C12h),
      and the elimination half-life in plasma (t1/2). The obtained pharmacokinetic
      parameters were compared with those of 12 patients using SQV HGC (400 mg twice
      daily) in combination with RTV (400 mg twice daily). RESULTS: The median values
      of the pharmacokinetic parameters for SQV SGC (1000 mg twice daily, normal
      breakfast) were: AUC0-12h, 18.84 h*mg/L; Cmax, 3.66 mg/L; C12h, 0.40 mg/L; and
      t1/2, 3.0 hours. The median values of the pharmacokinetic parameters for SQV HGC
      (400 mg twice daily, normal breakfast) were: AUC0-12h, 6.99 h*mg/L; Cmax, 1.28
      mg/L; C12h, 0.23 mg/L; and t1/2, 3.9 hours. The exposure to SQV in the dosing
      regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily was
      significantly higher than the exposure to SQV in a dosing regimen of 400 mg twice
      daily in combination with 400 mg of RTV twice daily. The pharmacokinetic
      parameters of SQV SGC in the dosing regimen of 1000 mg twice daily in combination
      with 100 mg of RTV twice daily were not significantly different after ingestion
      of a high-fat or normal breakfast (p >.35). CONCLUSIONS: The combination of 1000
      mg of SQV SGC twice daily and 100 mg of RTV twice daily resulted in a higher
      exposure to SQV compared with the exposure to SQV obtained when SQV is used in
      the 400 mg/400 mg twice-daily combination with RTV. In this small number of
      patients, no significant differences in exposure were seen after ingestion of
      either a normal or high-fat breakfast. From a pharmacokinetic perspective, the
      combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily seems
      to be a good option for further clinical evaluation.

PMID- 11468423
TI  - Comparison of virologic, immunologic, and clinical response to five different
      initial protease inhibitor-containing and nevirapine-containing regimens.
AB  - CONTEXT: The effectiveness of different protease inhibitors (PIs) and non
      nucleoside reverse transcriptase inhibitors outside the setting of clinical
      trials has not been well described. OBJECTIVES: To compare five different PI-and
      nevirapine (NVP)-containing regimens on virologic, immunologic, and clinical
      outcomes and treatment discontinuation. DESIGN AND SETTING: Observational cohort
      study based on an HIV clinic in London. PATIENTS: A total of 690 patients who
      received either saquinavir hard gel (SQV HG) (n = 183), indinavir (IDV) (n =
      189), nelfinavir (NFV) (n = 109), ritonavir (RTV) (n = 42), ritonavir with
      saquinavir hard gel (RTV/SQV HG) (n = 45), or NVP (n = 122) as part of an initial
      PI-or NVP-containing treatment regimen between November 1994 and December 1998. A
      total of 351 (51%) patients had prior exposure to nucleoside reverse
      transcriptase inhibitors (NRTIs). MAIN OUTCOME MEASURES: The main outcome
      measures were virologic undetectability, subsequent virologic rebound, CD4 cell
      count rise, development of AIDS, and treatment discontinuation. All analyses were
      stratified for year of initiation of the PI-or NVP-containing regimen. RESULTS:
      Overall, 63% of patients attained an undetectable viral load (VL) within 6 months
      of starting their PI or NVP regimen. The adjusted relative hazard (95% confidence
      interval [CI]) for an undetectable VL relative to SQV HG was (in rank order):
      2.77 (CI: 1.84-4.17) for NFV, 2.54 (CI: 1.81-3.57) for IDV, 2.43 (CI: 1.52-3.87)
      for RTV, 2.08 (CI: 1.28-3.37) for RTV/SQV HG, and 1.96 (CI: 1.35-2.85) for NVP.
      Forty-nine percent of patients experienced VL rebound within 12 months of initial
      attainment of undetectability, but relative to SQV HG, this did not differ
      significantly across the different PI and NVP regimens. The CD4 cell count
      response and rate of AIDS events were also similar across the different regimens.
      No independent predictors of VL undetectability were identified, but prior NRTI
      exposure was associated with VL rebound, and a lower baseline VL and CD4 cell
      count were associated with a reduced CD4 count response. The frequency (95% CI)
      of treatment discontinuation differed across the regimens; at 6 months, it was
      lowest for NFV (18% [CI: 13%-24%]), IDV (25% [CI: 22%-29%]), and NVP (28% [CI:
      22%-34%]) and highest for RTV (41% [CI: 31%-52%]) and SQV HG (52% [CI: 48%-57%]).
      CONCLUSIONS: Although PI- and NVP-containing regimens were similar in their CD4
      cell count response and rates of subsequent VL rebound, differences were observed
      in time to VL undetectability and discontinuation rates relative to SQV HG. SQV
      HG was consistently inferior to the other PIs and NVP. The use of NFV and IDV was
      associated with the highest rates of undetectability, and together with NVP, the
      lowest rates of discontinuation.

PMID- 11468424
TI  - Respiratory tract infection in HIV-1-infected adults in Nairobi, Kenya:
      evaluation of risk factors and the world health organization treatment algorithm.
AB  - To evaluate the WHO (World Health Organization) algorithm for management of
      respiratory tract infection (RTI) in HIV-1-infected adults and determine risk
      factors associated with RTI, we enrolled a cohort of 380 HIV-1-seropositive
      adults prospectively followed for incident RTI at an outpatient clinic in
      Nairobi, Kenya. RTI was diagnosed when patients presented with history of
      worsening or persistent cough. Patients were treated with ampicillin, or
      antituberculosis therapy when clinically indicated, as first-line therapy and
      with trimethoprim/sulfamethoxazole as second-line therapy. Five hundred ninety
      seven episodes of RTI were diagnosed: 177 of pneumonia and 420 of bronchitis. The
      WHO RTI algorithm was used for 401 (95%) episodes of bronchitis and 151 (85%)
      episodes of pneumonia (p <.001). Three percent of bronchitis cases versus 32% of
      pneumonia cases failed to respond to first-or second-line treatment (p <.0001).
      Being widowed (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI]: 1.0
      4.4), less than 8 years of education (adjusted OR = 2.5, CI: 1.5 - 4.1), and CD4
      count < 200 cells/microl (adjusted OR = 2.4, CI: 1.4-3.9) were risk factors for
      pneumonia. A high percentage of patients (32%) with pneumonia required a change
      in treatment from that recommended by the WHO guidelines. Randomized trials
      should be performed to determine more appropriate treatment strategies in HIV-1
      infected individuals.

PMID- 11468425
TI  - Clinical, biologic, and behavioral predictors of early immunologic and virologic
      response in HIV-infected patients initiating protease inhibitors.
AB  - Predictors of virologic (plasma HIV RNA viral load [VL] < 500 copies/ml) and
      immunologic (rise in CD4+ cell count > 50 cells/mm3) response after 4 months of
      therapy (M4) were studied in 750 HIV-1-infected patients prospectively enrolled
      at the initiation of a protease inhibitor (PI)-containing regimen. A virologic
      response was observed in 80% of patients, and an immunologic response was
      observed in 64%. Sixty-two percent of patients self-reported full adherence to
      therapy at 1 month of therapy (M1) and M4. In multivariate analysis, a virologic
      response was more frequent in fully adherent patients (odds ratio [OR] = 2.0; p
      =.001). An immunologic response was associated with age < 36 years (OR =1.4; p
      =.03), baseline VL (OR = 1.5 per 1 log10 copies/ml higher; p <.01), decrease in
      VL at M1 (OR = 1.5 per 1 log10 copies/ml decrease; p <.01), baseline total
      lymphocyte count (OR = 1.7 per 50% lower; p <.001), and baseline CD4+ cell
      percentage > or = 20% (OR =1.9; p <.001) but not with adherence to therapy. Full
      adherence seems to be a major predictor of a virologic response to PI-containing
      triple therapy. An immunologic response may be possible despite incomplete
      adherence, at least early in therapy.

PMID- 11468426
TI  - Genotypic correlates of a virologic response to stavudine after zidovudine
      monotherapy.
AB  - Prior evidence suggests that resistance to zidovudine (ZDV) confers some degree
      of cross-resistance to stavudine (d4T), but no genotypic correlates of clinical
      d4T susceptibility and resistance exist. To identify the genotypic correlates of
      a virologic response to d4T, reverse transcriptase (RT) sequencing of archived
      plasma HIV isolates was performed on 31 subjects who received d4T monotherapy in
      the AIDS Clinical Trials Group 302 study, all of whom received more than 3 years
      of ZDV monotherapy. Baseline characteristics and all RT mutations were analyzed
      for impact on virologic suppression. Eight of 31 subjects (27%) achieved a
      virologic response of greater than 0.3 log reduction in plasma HIV RNA after 8
      weeks of d4T. Responders were more likely to have lower median baseline viral
      loads (4.2 vs. 4.7; p =.01) and a trend toward fewer ZDV-associated mutations
      (median: 1 vs. 2; p =.09). No subject with greater than one ZDV mutation had a
      virologic response to d4T. Seven of the 8 responders had only a K70R mutation at
      baseline. We conclude that in patients with prior ZDV treatment, those with only
      one ZDV mutation, particularly at position 70, can still get reasonable virologic
      activity from d4T. Those with more mutations are not likely to have much benefit.

PMID- 11468427
TI  - Knowledge about vaccine trials and willingness to participate in an HIV/AIDS
      vaccine study in the Ugandan military.
AB  - In preparation for HIV vaccine trials, knowledge about vaccines, willingness to
      participate in a vaccine study, and motivations for participation must be
      assessed. The Preparation for AIDS Vaccine Evaluation study assessed knowledge
      about vaccines and vaccine trials and willingness to participate in a
      hypothetical trial in 1,182 Ugandan military men (aged 18-30 years). Participants
      received education about vaccine trials and were interviewed during 24 months of
      follow-up observation. Its key findings are that: 1) throughout follow-up, most
      participants expressed willingness to participate in a hypothetical HIV vaccine
      trial; 2) participants are familiar with vaccines but do not clearly distinguish
      the use of vaccines for prevention or curing; 3) the most common reason given for
      being interested in participating in a vaccine trial was to be protected from
      HIV/AIDS; 4) trials' procedures (e.g., placebos, randomization, and blinding)
      were unfamiliar; and 5) knowledge about trials' procedures increased
      incrementally over follow-up, but at different rates for different concepts.
      These data demonstrate that potential vaccine trials' participants may benefit
      from vaccine trial education if adequate time is allowed to ensure that
      participants are able to master the complex information required for trial
      participation.

PMID- 11468428
TI  - Immune activation correlates better than HIV plasma viral load with CD4 T-cell
      decline during HIV infection.
AB  - This study addressed the role of T-cell immune activation in determining HIV-1
      plasma viral load and CD4+ T-cell blood levels during HIV-1 infection. A decrease
      of blood CD4 levels and CD4/CD8 ratios and an increase of CD8 levels in both
      treated (n = 35) and untreated (n = 19) HIV-positive individuals were more
      strongly correlated to immune activation (log percentage of HLA-DR+CD3+ cells; R
      = -0.78, R = -0.77, and R = 0.58, respectively; p <.0001) than to CD4 T-cell
      proliferation (log percentage of Ki-67+CD4+ cells; R = -0.57 [p <.0001], R = 
      0.48 [p <.001], and R = 0.37 [p <.01], respectively) or to viral load (R = -0.36
      [p <.01], R = -0.23 [p =.09], R = 0.13 [p =.35], respectively). Because almost
      half of the Ki-67+CD4+ cells were also positive for CTLA-4 (a marker for
      activated nonproliferating cells), the correlation of CD4 levels to Ki-67
      expression is only partially related to cell proliferation and more likely
      represents mainly immune activation of the cells without proliferation. Taken
      together, these results suggest that immune activation is the major determinant
      of CD4 decline and should therefore be considered central for the monitoring of
      HIV infection and its outcome after antiviral treatment.

PMID- 11468429
TI  - Patterns of needle acquisition and sociobehavioral correlates of needle exchange
      program attendance in Baltimore, Maryland, U.S.A.
AB  - OBJECTIVES: This study examined factors associated with obtaining syringes from a
      needle exchange program (NEP) and other safer sources in Baltimore, Maryland,
      U.S.A. DESIGN AND METHODS: A cross-sectional face-to-face survey was administered
      to 741 current drug injectors recruited by snowball sampling techniques. A brief
      open-ended interview was conducted on a subsample. RESULTS: Most (85%)
      participants obtained needles from street needle sellers. Only 8% obtained their
      needles exclusively from safer sources (NEPs, pharmacies, hospitals, or patients
      with diabetes). Cocaine use was associated with obtaining needles from the NEP
      but not from exclusively safer sources. Obtaining needles from only safer sources
      was associated with being female and less frequent needle sharing and shooting
      gallery attendance. Among HIV-seropositive participants, those who were diagnosed
      before the year that the NEP began were more likely to obtain needles from safer
      sources. Participants who sold needles reported that it was easy to make used
      needles appear to be unused, and some admitted to selling used syringes as new.
      CONCLUSIONS: Street needle sellers are an important source of needles for drug
      injectors, and few injectors appear able to determine whether these needles are
      clean. Individual sealing of diabetic syringes may reduce the risk of blood-borne
      infections by enabling both drug injectors and patients with diabetes to better
      judge the sterility of the needles they purchase.

PMID- 11468430
TI  - Between-city variation in frequency of injection among Puerto Rican injection
      drug users: East Harlem, New York, and Bayamon, Puerto Rico.
AB  - Frequency of injection has been consistently found to be higher among Puerto
      Rican Injection drug users (IDUs) than among other groups of IDUs. Several
      explanations have been suggested, but an empirical explanation has yet to be
      presented. This study compares the frequency of injection of Puerto Rican IDUs in
      East Harlem, New York, with that of IDUs in Bayamon, Puerto Rico. Study subjects
      comprised 521 Puerto Rican IDUs from East Harlem and 303 IDUs from Bayamon. The
      mean frequency of injection among IDUs in East Harlem was 2.8, the corresponding
      mean in Bayamon was 5.4. Younger IDUs reported a higher number of daily injection
      episodes than older IDUs, and the IDU group in Bayamon was 5 years younger than
      the group in East Harlem. The drug use variables accounted for a greater portion
      of the between-city difference than the demographic and psychosocial variables.
      Use of noninjected drugs, as well as the use of prescribed methadone, were found
      to be associated with a lower number of daily injections. Conversely, injection
      of cocaine, injection of cocaine mixed with heroin ("speedball"), and injection
      of larger amounts of drug solution were found to be associated with a higher
      number of daily injections.

PMID- 11468431
TI  - Risk factors for HIV among northern Thai women: testing hypotheses or repeating
      assumptions?

PMID- 11468433
TI  - Natural progression of untreated hepatolithiasis.

PMID- 11468434
TI  - Adult living donor liver transplantation: current status.
AB  - Living donor liver transplantation was developed in response to a shortage of
      full-size grafts for children. The progression from reduced-size cadaveric grafts
      to use of living donors occurred subsequent to expansion of liver anatomy
      knowledge and practical use of hepatic segments. A major benefit of pediatric
      live donor liver transplantation is the grafting of children without using livers
      from the cadaver donor pool. A major drawback of the procedure relates to the
      need to perform surgery and assign risk to an otherwise healthy individual. The
      ethical challenge has been discussed in detail and, although not ideal, the
      procedure "passes muster" on grounds of informed consent and the good of helping
      another human being. Formidable success appears to have been attained with the
      adult-to-adult procedure thus far; however, the transplant community still awaits
      center-specific and compiled data to determine whether the procedure truly
      reduces adult waiting list times for liver transplant recipients with minimal
      donor risk.

PMID- 11468435
TI  - Lessons learned from intragastric pH monitoring.
AB  - Management of gastroesophageal reflux disease (GERD) is based on the concept that
      gastric contents, principally acid and pepsin, are responsible for esophageal
      injury and symptoms of reflux disease. Pharmacologic management in the year 2001
      revolves around the basic principle that control of intragastric pH correlates
      with esophageal healing and, subsequently, symptom relief. Although the majority
      of patients respond to a single daily dose of a proton pump inhibitor, many
      patients with reflux disease are "refractory" even to twice daily doses of these
      drugs. Potential reasons for this less than optimal response can be found when
      carefully examining the intragastric pH responses of healthy subjects and
      patients with GERD to these agents when taken at various times of the day, in
      proximity to meals, and in higher doses. In the past several years, we have
      explored many of these issues in attempting to understand the mechanisms behind
      incomplete response to proton pump inhibitors, using combined intragastric and
      intraesophageal pH monitoring. The "lessons learned" from these and supportive
      studies are the subject of this review.

PMID- 11468436
TI  - Natural progression of untreated hepatolithiasis that shows no clinical signs at
      its initial presentation.
AB  - GOALS: To elucidate the natural progression of hepatolithiasis that showed no
      signs at the time of initial presentation. STUDY: Over a 17-year period, we
      observed 122 of 311 patients with hepatolithiasis who reported no symptoms and,
      thus, who received no treatment at initial presentation. The follow-up period was
      for up to 15 years (mean, 10.08 years). RESULTS: Fourteen of 112 patients (11.5%)
      developed some symptoms attributed to hepatolithiasis. The interval until the
      onset of symptoms ranged from 9 months to 7.33 years (mean, 3.42 years ). The
      developing symptoms included abdominal pain, hepatic abscess, cholangitis, and
      cholangiocarcinoma. Nine of the 14 patients (64.3%) developed stone migration to
      the extrahepatic bile duct at the onset of clinical symptoms. The incidence of
      lobar liver atrophy on computed tomography in the patients with symptomatic
      hepatolithiasis (13 of 14 patients; 92.9%) was significantly higher than that in
      the patients with asymptomatic hepatolithiasis (14 of 108 patients; 13.0%). The
      prognosis of the patients with symptomatic hepatolithiasis were as follows: 2
      died of cholangiocarcinoma, 1 died of hepatic failure, and 11 survived. Fifteen
      of asymptomatic patients died, but none of these deaths were attributed to
      hepatolithiasis. CONCLUSIONS: Close observation is an alternative management at
      initial presentation for patients with asymptomatic hepatolithiasis without
      extrahepatic stones or lobar liver atrophy.

PMID- 11468437
TI  - Plasma isocitrate dehydrogenase as a marker of centrilobular hepatic necrosis in
      patients with hyperthyroidism.
AB  - Isocitrate dehydrogenase (ICDH) may be useful for differentiating centrilobular
      from periportal necrosis in rats with liver injury. In this study, we assessed
      the usefulness of ICDH as a marker of centrilobular necrosis in patients with
      hyperthyroidism. Isocitrate dehydrogenase and alanine aminotransferase (ALT)
      activities were measured in the plasma of 56 patients with hyperthyroidism, 16
      patients with chronic viral hepatitis (CVH), and 17 controls. Isocitrate
      dehydrogenase levels were higher in patients with hyperthyroidism than in those
      with CVH or in the controls (p < 0.01 and p < 0.001, respectively), even though
      ALT levels were higher in patients with CVH than in patients with hyperthyroidism
      (p < 0.01). Isocitrate dehydrogenase/ALT ratios were also higher in patients with
      hyperthyroidism than in those with CVH (p < 0.0001). Isocitrate dehydrogenase
      correlated to ALT levels in patients with hyperthyroidism or CVH (p < 0.05). In a
      patient with hyperthyroidism, ICDH levels decreased progressively to normal, and
      the ALT level and thyroid function were normalized. Thus, the plasma ICDH or
      ICDH/ALT ratio might be useful for differentiating centrilobular from periportal
      necrosis and for monitoring the degree of hepatic necrosis in patients with
      hyperthyroidism.

PMID- 11468438
TI  - The role of hepatitis C in hepatocellular carcinoma: a case control study among
      Egyptian patients.
AB  - BACKGROUND: Egypt has one of the highest prevalence rates of hepatitis C virus
      (HCV) infection in the world; however, the risk and attribution related to HCV in
      Egyptian patients with hepatocellular carcinoma (HCC) remains unknown. GOALS: The
      current study was undertaken to estimate the risk of HCC in relation to HCV in
      Egypt. STUDY: Thirty-three patients with HCC and 35 healthy controls who had a
      similar socioeconomic status were prospectively enrolled at the University of
      Cairo National Cancer Institute. RESULTS: Anti-HCV antibodies were present in
      75.8% of the patients and in 42.9% of the controls (p = 0.01); hepatitis B
      surface antigen (HBsAg) was present in 15.2% of the patients and in 2.9% of the
      controls (p = 0.03). In addition, the sex-and age-adjusted odds ratio (OR) for
      anti-HCV antibodies was 5.1 (95% CI = 1.5-17.4) and for HBsAg was 13.2 (95% CI =
      1.2-148.2). Concurrent Schistosoma mansoni and anti-HCV was associated with an OR
      of 10.3 (95% CI = 1.3-79.8), which was higher than that for anti-HCV (6.5; 95% CI
      = 1.6-26.6) and S. mansoni infection (0.2; 95% CI = 0.1-6.2) alone. Finally, we
      estimated the attributable fraction of HCC to HCV to be 64% in this study
      population and 48% in the general Egyptian population. CONCLUSIONS: Both HCV and
      hepatitis B virus infection increase the risk of HCC in Egyptian patients,
      whereas isolated Schistosoma infection does not. Because of the very high
      prevalence rate of HCV in the general Egyptian population, it accounts for most
      HCC cases in Egypt.

PMID- 11468439
TI  - The correlation of depression and gastric dysrhythmia in functional dyspepsia.
AB  - Psychologic factors in functional dyspepsia have been discussed in many previous
      articles. However, the relationship between depression and functional dyspepsia
      is still obscure. We investigated the impact of depression on clinical symptoms
      and gastric dysrhythmia in functional dyspepsia. Thirty-nine patients with
      functional dyspepsia and 18 healthy subjects were included. Patients were
      investigated with clinical symptoms assessment, Zung's self-rating depression
      scale, and electrogastrography. Patients with functional dyspepsia were divided
      into two groups: 21 patients with depression and 18 patients without depression.
      The depressed patients had similar total gastrointestinal symptom severity scores
      compared with the nondepressed patients, but with higher total symptom frequency
      scores (p < 0.05). With regards to symptoms, the depressed patients had higher
      abdominal fullness severity and frequency scores and nausea frequency scores. The
      patients with functional dyspepsia had a lower percentage of normal slow wave in
      both the fasting and fed states and a higher percentage of bradygastria in the
      fasting state and tachygastria in the postprandial state (p < 0.05). There was no
      significant difference in the percentage of bradygastria or tachygastria between
      the depressed and nondepressed patients. There was no correlation between the
      specific type of electrogastrographic abnormality and the presence or absence of
      depression in functional dyspepsia patients.

PMID- 11468440
TI  - Terminal ileum resection is associated with higher plasma homocysteine levels in
      Crohn's disease.
AB  - BACKGROUND: Elevated plasma total homocysteine (tHcy) is associated with a higher
      risk of thrombosis. Crohn's disease (CD) is associated with hypercoagulability of
      undefined etiology. We investigated tHcy in patients with CD and its relationship
      with vitamin status, disease activity, location, duration, and history of
      terminal ileum (TI) resection. STUDY: We examined fasting plasma tHcy, folate,
      serum vitamin B12 levels, and sedimentation rate in consecutive adult patients
      with CD. Harvey-Bradshaw index of CD activity and history of TI resection and
      thromboembolism were recorded. RESULTS: Median plasma tHcy was 10.2 micromol/L in
      125 patients with CD. Men (n = 60) had higher plasma tHcy than women (n = 65)
      (11.2 vs. 9.1 micromol/L; p = 0.004). Patients with a history of TI resection
      showed lower serum B12 levels (293 vs. 503 pg/mL; p < 0.001) and higher plasma
      tHcy levels (11.0 vs. 9.35 micromol/L; p = 0.027) than patients without such
      history. Multivariate analysis showed history of TI resection, serum B12, and
      creatinine levels to be significant predictors of elevated plasma tHcy. Fourteen
      patients with CD with a history of thrombosis had an elevated median plasma tHcy
      of 11.6 micromol/L. CONCLUSIONS: Terminal ileum resection contributes to elevated
      plasma tHcy levels in CD cases. We recommend tHcy screening in patients with CD,
      especially in those with prior history of TI resection, and the initiation of
      vitamin supplementation when appropriate.

PMID- 11468441
TI  - The benefit of long-term interferon alfa therapy for symptomatic mixed
      cryoglobulinemia (cutaneous vasculitis/membranoproliferative glomerulonephritis)
      associated with chronic hepatitis C infection.
AB  - The efficacy of long-term interferon therapy for chronic hepatitis C infection
      with symptomatic mixed cryoglobulinemia has not clearly been defined. We describe
      a patient with chronic hepatitis C, symptomatic mixed cryoglobulinemia (cutaneous
      vasculitis), and membranoproliferative glomerulonephritis (MPGN) who responded
      clinically, biochemically, and virologically to a 1-year course of interferon
      therapy. Interferon side effects were minimal. Relapse occurred when interferon
      was discontinued, and suppressive maintenance interferon therapy was required for
      clinical, biochemical, and virologic remission. During the 5th year of
      maintenance therapy, she developed potential side effects that necessitated
      discontinuation of interferon treatment. After treatment stoppage, a clinical,
      biochemical, and virologic remission was maintained for more than 1 year.
      However, the potential side effects, which included eye irritation, arthralgias,
      myalgias, fatigue, insomnia, memory loss, and depression, persisted.
      Ophthalmologic, rheumatologic, and neurologic evaluations were nondiagnostic.
      Psychometric testing revealed dementia and mood disorder. Because the disabling
      symptoms persisted after 9 months, a health-related quality of life assessment
      was carried out with the SF-36 survey. Compared with healthy individuals and
      patients with chronic hepatitis C, our case had a lower health-related quality of
      life assessment on six out of seven scales and on four out of seven scales of the
      SF-36 survey, respectively. This case report indicates that long-term maintenance
      interferon therapy was effective in the treatment of symptomatic mixed
      cryoglobulinemia and its renal complications and resulted in a clinical,
      biochemical, and virologic sustained response. It is postulated that the side
      effects of long-term interferon therapy in this setting may be problematic.

PMID- 11468442
TI  - Barrett's adenocarcinoma of the esophagus with lymphoid stroma.
AB  - We report a case of Barrett's adenocarcinoma of the esophagus with lymphoid
      stroma. We believe this is the first reported case of this entity, although six
      previous cases of esophageal lymphoepithelioma-like carcinoma have been reported.
      The esophageal tumor from a 58-year-old man was examined histologically. In situ
      hybridization to detect Epstein-Barr virus (EBV) was also performed. The tumor
      consisted of a poorly differentiated adenocarcinoma with dense lymphoid cell
      infiltration in the invasive portions and a well-differentiated adenocarcinoma
      without lymphoid stroma in the mucosa. Barrett's epithelium was observed adjacent
      to the carcinoma. No positive signals for EBV were detected in the tumor cells.
      Six previously reported patients with esophageal lymphoepithelioma-like
      carcinomas, and the current patient, all survived for longer than 24 months, a
      better outcome than that of patients with esophageal squamous cell carcinomas of
      usual type. The data suggest that this tumor arose as a mucosal, well
      differentiated adenocarcinoma without lymphoid stroma and that EBV had no
      relation to either its pathogenesis or progression.

PMID- 11468443
TI  - Refractory gastrointestinal bleeding treated with thyroid hormone replacement.
AB  - Although bleeding diathesis has been associated with hypothyroidism, refractory
      gastrointestinal bleeding has not been previously described in association with
      hypothyroidism. We report a patient who presented with refractory
      gastrointestinal bleeding over an 8-week period. Extensive work-up demonstrated
      small intestinal vascular malformations as the source of bleeding. Despite
      endoscopic therapy and hormonal therapy, bleeding continued and required
      transfusion of 54 units of packed red blood cells. Surgical therapy was offered
      to the patient but was declined. Ultimately, correction of the patient's
      underlying hypothyroidism resulted in cessation of gastrointestinal bleeding, and
      no further blood transfusion was necessary. To date, the patient has remained
      euthyroid without further gastrointestinal bleeding for 30 months.

PMID- 11468444
TI  - Synchronous double cancer of the stomach and rectum with situs inversus totalis
      and polysplenia syndrome.
AB  - Situs solitus refers to the normal arrangement of body organs. Situs inversus
      totalis is a complete mirror image or reverse isomeric form of the thoracic and
      abdominal viscera. Any arrangement of organs between these two extremes is
      designated by heterotaxia. Several patterns of vascular and visceral
      abnormalities are associated with heterotaxia, and two loosely defined syndromes
      of splenic anomalies (asplenia and polysplenia) are most common. We present the
      case of a 71-year-old woman with situs inversus totalis and polysplenia syndrome
      who developed synchronous double cancer originating from the stomach and rectum.
      Abdominal manifestations were situs inversus totalis combined with multiple
      lobulated spleen, azygous continuation of the interrupted inferior vena cava,
      direct drainage of hepatic vein to left atrium, preduodenal portal vein, short
      pancreas, incomplete rotation of the colon, and malrotation of the intestine.
      Histologically, gastric cancer was diagnosed as papillary adenocarcinoma and
      rectal cancer, as moderately differentiated adenocarcinoma. The patient was
      successfully treated with total gastrectomy for gastric cancer and low-anterior
      resection of the rectum for rectal cancer.

PMID- 11468445
TI  - Periampullary gangliocytic paraganglioma.
AB  - A33-year-old man presented with features of obstructive jaundice. Enterohepatic
      retrograde cholangiopancreatography examination revealed a periampullary growth.
      After pancreatoduodenectomy, histologic examination of the growth revealed three
      elements: a spindle cell element, large ganglion cells, and smaller paraganglioma
      like cells arranged in small nests and groups. A diagnosis of gangliocytic
      paraganglioma was given. Gangliocytic paraganglioma is a rare benign duodenal
      tumor, with uncertain histogenesis. It is possible to identify the three
      components that are essential for its diagnosis on routine hematoxylin and eosin
      sections without the use of immunohistochemical markers. Because this lesion may
      present clinically as a periampullary carcinoma, it is important to recognize and
      diagnose this rare, but benign, entity.

PMID- 11468446
TI  - Enalapril-induced eosinophilic gastroenteritis.
AB  - Eosinophilic gastroenteritis is a rare disorder of unknown etiology. We describe
      a case of a 63-year-old woman with chronic diarrhea and eosinophilia. Small bowel
      biopsy revealed eosinophils in large clusters in the lamina propria with focal
      infiltration of the epithelium. The patient's diarrhea and eosinophilia started
      shortly after enalapril was prescribed. When the patient was instructed to stop
      taking that drug, her diarrhea promptly ceased, and the blood eosinophil level
      returned to normal. This is the first reported case of eosinophilic
      gastroenteritis associated with an angiotensin-converting enzyme inhibitor.
      Eosinophilic gastroenteritis should be entertained in the differential diagnosis
      of patients taking angiotensin-converting enzyme inhibitors who develop diarrhea
      or other gastrointestinal symptoms.

PMID- 11468447
TI  - Ischemic colitis associated with paclitaxel.
AB  - Systemic chemotherapy can be complicated by colonic toxicity, which usually
      determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis
      in patients with cancer. This report describes the case of a 49-year-old woman
      with liver metastases from a neuroendocrine tumor of unknown origin who developed
      mild ischemic colitis after chemotherapy with carboplatin and paclitaxel. The
      patient developed symptoms of gastrointestinal toxicity with abdominal pain and
      bloody diarrhea, which resolved in about 10 days. She had a normal white blood
      cell count throughout her illness; the assay of stool specimens for Clostridium
      difficile toxins and the stool cultures were both negative. A sigmoidoscopy
      showed a mild, transient ischemic colitis, which was confirmed by pathologic
      examination of the biopsy specimens. Although carboplatin is not related to
      severe colonic cytotoxicity, it has been previously reported that paclitaxel
      induces necrosis of the gastrointestinal mucosa and inhibits angiogenesis.
      Pseudomembranous colitis is the most frequent complication in patients with
      cancer who undergo paclitaxel-based chemotherapy and develop gastrointestinal
      toxicity. Once C. difficile infection has been excluded, a diagnosis of ischemic
      colitis should be considered, especially in patients with cancer who have normal
      white blood cell counts.

PMID- 11468448
TI  - Tracheobronchitis as an initial presentation of ulcerative colitis.
AB  - We describe a patient with ulcerative colitis (UC) and the rare extraintestinal
      manifestation of fulminant tracheobronchitis. A 50-year-old man presented with
      respiratory compromise and bloody diarrhea. His evaluation showed large airway
      inflammation with fibrinopurulent debris and colonic inflammation and ulcerations
      consistent with UC. The etiology for the pulmonary pathology was thoroughly
      investigated and was thought to be an extraintestinal manifestation of the UC.

PMID- 11468449
TI  - The watermelon rectum.
AB  - This is the first reported case of rectal vascular ectasia in association with
      gastric antral vascular ectasia (watermelon stomach). The patient, a 39-year-old
      woman with systemic sclerosis, reported chronic gastrointestinal blood loss and
      iron deficiency anemia. She had aperistalsis of the distal esophagus, decreased
      lower esophageal sphincter pressure leading to severe gastroesophageal reflux,
      and dysmotility of the small intestine. Diagnosis was made by endoscopic
      appearance of visible linear watermelon-like vascular stripes in the gastric
      antrum and rectum. Histology confirmed the vascular nature of this disorder,
      showing dilated and thrombosed capillaries in the lamina propria. Gastric biopsy
      showed associated fibromuscular hyperplasia in the lamina propria. However, the
      colonic biopsy showed only focal hyalinization in the lamina propria. The patient
      was successfully treated using endoscopic bipolar electrocautery. Watermelon
      stomach has previously been described in association with systemic sclerosis.
      Based on the histopathologic similarity between rectal vascular ectasia, gastric
      antral vascular ectasia, and systemic sclerosis, we suggest that the rectal
      vascular lesion may represent a component of the gastrointestinal manifestations
      of systemic sclerosis.

PMID- 11468450
TI  - Biliary giardiasis in a patient with human immunodeficiency virus.
AB  - A 41-year-old man with human immunodeficiency virus (HIV) (CD4 count, 446/mm3)
      developed a protracted course of abdominal pain, weight loss, and increasing
      liver function tests after undergoing a metronidazole treatment regimen for
      Giardia enteritis. Three months later, endoscopic retrograde cholangiography
      (ERCP) showed dilated common and intrahepatic bile ducts and luminal
      irregularities of the common bile duct. Seven months after the onset of his acute
      diarrhea, a repeat ERCP with aspiration demonstrated many Giardia trophozoites
      and cysts in the bile and continued structural abnormalities consistent with
      cholangiopathy. A 10-day course of high-dose intravenous metronidazole did not
      resolve these signs or symptoms. A gallbladder ultrasound showed a thickened
      wall. Laparoscopic cholecystectomy led to resolution of abdominal pain and
      normalization of serum alkaline phosphatase over an 8-month period. Gallbladder
      histopathology revealed chronic cholecystitis, but no parasites were seen on
      hematoxylin and eosin staining or with Giardia antigen enzyme immunoassay testing
      of the gallbladder. The patient refused to undergo a follow-up ERCP, but a right
      upper quadrant ultrasound and computed tomography of the abdomen were normal.

PMID- 11468451
TI  - Subcutaneous seeding of hepatocellular carcinoma after fine-needle percutaneous
      biopsy.

PMID- 11468452
TI  - Symptomatic hypothyroidism in decompensated liver cirrhosis.

PMID- 11468453
TI  - Watermelon stomach arising in association with Addison's disease.

PMID- 11468454
TI  - The effectiveness of one-week triple eradication therapy for perforated duodenal
      ulcer patients treated with simple closure.

PMID- 11468455
TI  - Behcet's disease complicated with celiac trunk aneurysm.

PMID- 11468456
TI  - Mucinous adenocarcinoma arising in chronic perianal fistulas.

PMID- 11468457
TI  - Correlation between crash severity, injury severity, and clinical course in car
      occupants with thoracic trauma: a technical and medical study.
AB  - BACKGROUND: The crash mechanisms and clinical course of car occupants with
      thoracic injury were analyzed to determine prognostic factors and to create a
      basis for injury prophylaxis. METHODS: A technical and medical investigation of
      car occupants with a thoracic injury (Abbreviated Injury Scale-thorax
      [AIS(THORAX)] > or = 1) at the scene of the crash and the primary admitting
      hospital was performed. RESULTS: Between 1985 and 1998, 581 car occupants
      sustained a thoracic injury. Mean parameter values were as follows: AIS(THORAX),
      2.5; Hannover Polytrauma Score (PTS), 21.4; Injury Severity Score (ISS), 24.2;
      Delta-v, 49.6 km/h (30.8 mph); and extent of passenger compartment deformation
      (DEF) (scale, 1--9), 4.0. In 19% (n = 112) of patients involved, the clinical
      course was evaluated: AIS(THORAX), 2.5; PTS, 20.0; ISS, 19.3; Delta-v, 50.1 km/h
      (31.1 mph); DEF, 3.9; intensive care unit time, 8.3 days; ventilation time, 5.7
      days; and hospital stay, 15.3 days. In the groups with higher AIS(THORAX), ISS,
      PTS, and intensive care unit and ventilation time, higher Delta-v and DEF
      occurred. In patients with longer hospital stay, higher Delta-v, but no
      difference in DEF occurred. CONCLUSION: The injury severity and the clinical
      course demonstrated a positive correlation with the crash severity. Therefore,
      our technical accident analysis allows prediction of the severity of injury and
      the clinical course. It may consequently serve as a tool for development of more
      sophisticated injury prevention strategies and may improve passive car safety.

PMID- 11468458
TI  - Trauma outcome analysis of a Jakarta University Hospital using the TRISS method:
      validation and limitation in comparison with the major trauma outcome study.
      Trauma and Injury Severity Score.
AB  - BACKGROUND: In this prospective study, the TRISS methodology is used to compare
      trauma care at a University Hospital in Jakarta, Indonesia, with the standards
      reported in the Major Trauma Outcome Study (MTOS). METHODS: Between February 24,
      1999, and July 1, 1999, all consecutive patients with multiple and severe trauma
      were included in the study (n = 105). Survival analysis was completed for 97
      (92%) patients. RESULTS: The majority of patients were men (81%), and the average
      age was 28 years. Ninety-five patients (98%) sustained blunt trauma, with motor
      vehicle crashes being the most common (68%). The predicted mortality was 14% and
      the observed mortality was 29%. The Z and M statistics were 7.87 and 0.843,
      respectively. CONCLUSION: We conclude that in developing countries both
      institution-bound factors and specific limitations in the TRISS methodology are
      responsible for the difference between predicted and observed mortality,
      indicating the need for a regional database.

PMID- 11468459
TI  - Near-infrared spectroscopy versus compartment pressure for the diagnosis of lower
      extremity compartmental syndrome using electromyography-determined measurements
      of neuromuscular function.
AB  - BACKGROUND: Compartmental syndrome (CS) is difficult to diagnose in intensive
      care unit patients. Compartment perfusion pressure (CPP) is an invasive, indirect
      measure of ischemia. Near-infrared spectroscopy is noninvasive, and directly
      measures ischemia by transmitting light through tissues at wavelengths that react
      with hemoglobin to provide percent tissue oxygen saturation (Sto(2)). Animal
      studies demonstrate that Sto(2) is superior to CPP for detecting CS. However,
      there are no studies in humans comparing Sto(2) with CPP. We hypothesized that
      Sto(2) can reliably detect CS, and is superior to CPP. METHODS: CS was induced in
      15 human volunteers using a standard calf compression model. At 30-minute
      intervals, compression was increased to reduce Sto(2) from baseline (86% +/- 4%)
      to 60%, 40%, 20%, and < 10%, with simultaneous recording of CPP. Outcome
      variables included deep peroneal nerve conduction assessed by electromyography,
      cutaneous peroneal nerve sensitivity using Semmes-Weinstein monofilaments, and
      pain (visual analog scale). RESULTS: Both Sto(2) and CPP significantly correlated
      with all ischemia outcome variables (p < 0.001). Receiver operating
      characteristic curves of deep peroneal nerve conduction demonstrated that Sto(2)
      had higher sensitivity than CPP for detecting > 50% block. For example, when
      specificity was 83% for Sto(2) and 84% for CPP, sensitivity was 85% versus 56%,
      respectively (p = 0.02). When specificity for both was 72%, sensitivity was 94%
      for Sto(2) versus 76% for CPP (p = 0.04). CONCLUSION: In intensive care unit
      patients who cannot alert physicians to symptoms, near-infrared spectroscopy may
      help clinicians to avoid delayed or unnecessary prophylactic fasciotomy, and
      provides the benefits of a continuous, noninvasive monitoring technique.

PMID- 11468460
TI  - Use of a human patient simulator in the development of resident trauma management
      skills.
AB  - BACKGROUND: Computerized human patient simulators (HPSs) have been used to
      improve diagnostic and therapeutic decision making. The goal of this study was to
      investigate the impact of HPSs and Advanced Trauma Life Support (ATLS) on the
      development of trauma management skills and self-confidence in surgical interns.
      METHODS: Three teams of interns completed two ATLS-like trauma scenarios on the
      HPS (pre-ATLS). They then took the ATLS provider course. After ATLS, the interns
      were evaluated on two different HPS trauma scenarios (post-ATLS). Two teams of
      senior residents, experienced in trauma care, completed the same HPS scenarios
      and were used as controls. Trauma management skills were scored in three areas-
      critical treatment decisions, potential for adverse outcomes, and team behavior-
      by staff trauma surgeons. After participating in the HPS trauma scenarios, the
      interns completed self-confidence questionnaires and a course evaluation survey.
      RESULTS: Trauma management skill scores increased 23% in critical treatment
      decisions, 25% in potential for adverse outcomes, and 47% in team behavior after
      ATLS/HPS (p < 0.002). Senior residents' performance on HPS trauma scenarios was
      better than the interns (p < 0.05) in all three areas evaluated. The interns'
      self-confidence scores rose significantly after the course. (p < 0.01) The HPS
      course evaluation survey averaged 8.3 out of a maximum 10. CONCLUSION: Use of
      HPSs in conjunction with ATLS appears to enhance the development of trauma
      management skills. The surgical interns participating in the study deemed the HPS
      to be a worthwhile experience and a confidence-building tool. In particular,
      trauma team behavior improved significantly after ATLS/HPS.

PMID- 11468462
TI  - Effects of deferoxamine on tissue superoxide dismutase and glutathione peroxidase
      levels in experimental head trauma.
AB  - BACKGROUND: This study aims to evaluate the effects of deferoxamine on tissue
      superoxide dismutase (SOD) and glutathione peroxidase (GPx) brain levels after
      head trauma. METHODS: Thirty rabbits were divided equally into three groups:
      group 1 was the sham-operated group, group 2 suffered head trauma (no treatment
      was given), and group 3 received deferoxamine 50 mg/kg after the trauma. Head
      trauma was applied unilaterally. One hour after trauma, brain cortices were
      resected and SOD and GPx levels were determined. One-way analysis of variance and
      Tukey-HSD tests were used for analysis. Significance was defined as p < 0.05.
      RESULTS: Baseline SOD levels are preserved in the traumatized side of the
      deferoxamine-treated group. Although GPx level of the traumatized side of the
      deferoxamine-treated group decreased significantly, the decrease was
      significantly less than the nontreated group. CONCLUSION: Trauma leads to a
      decrease in brain tissue SOD and GPx levels. Deferoxamine suppresses this
      decrease completely in SOD level and partially in GPx level when given after
      trauma.

PMID- 11468463
TI  - Helical computed tomography of bowel and mesenteric injuries.
AB  - BACKGROUND: The role of computed tomography in diagnosing hollow viscus injury
      after blunt abdominal trauma remains controversial, with previous studies
      reporting both high accuracy and poor results. This study was performed to
      determine the diagnostic accuracy of helical computed tomography in detecting
      bowel and mesenteric injuries after blunt abdominal trauma in a large cohort of
      patients. METHODS: One hundred fifty patients were admitted to our Level I trauma
      center over a 4-year period with computed tomographic (CT) scan or surgical
      diagnosis of bowel or mesenteric injury. CT scan findings were retrospectively
      graded as negative, nonsurgical, or surgical bowel or mesenteric injury. The CT
      scan diagnosis was then compared with surgical findings, which were also graded
      as negative, nonsurgical, or surgical. RESULTS: Computed tomography had an
      overall sensitivity of 94% in detecting bowel injury and 96% in detecting
      mesenteric injury. Surgical bowel cases were correctly differentiated in 64 of 74
      cases (86%), and surgical mesenteric cases were correctly differentiated from
      nonsurgical in 57 of 76 cases (75%). CONCLUSION: Helical CT scanning is very
      accurate in detecting bowel and mesenteric injuries, as well as in determining
      the need for surgical exploration in bowel injuries. However, it is less accurate
      in predicting the need for surgical exploration in mesenteric injuries alone.

PMID- 11468464
TI  - Discriminatory power of 3.5 MHz convex and 7.5 MHz linear ultrasound probes for
      the imaging of traumatic splenic lesions: a feasibility study.
AB  - BACKGROUND: Ultrasound is a powerful tool for recognition of free fluid after
      blunt abdominal trauma, whereas its role for detection of organ lesions remains
      to be defined. The objective of this study was to determine the diagnostic value
      of different ultrasound transducers for the precise detection of visceral damage
      rather than its surrogates in case of splenic injury. METHODS: After a
      standardized focused abdominal sonogram for trauma protocol to screen for
      hemoperitoneum, 37 slim, hemodynamically stable subjects with suspected torso
      trauma were investigated for the extent of parenchymal lesions of the spleen
      using a 3.5 MHz curved array and a 7.5 MHz linear device. Helical computed
      tomographic scanning was carried out as the reference standard in all cases.
      RESULTS: Twenty patients presented splenic damage. The 7.5 MHz transducer showed
      higher accuracy than the lower frequency probe for the detection of tissue
      irregularities (difference in proportions, 16.2%; 95% confidence interval, -1.9%
      33.5%). A similar trend was observed for 13 lacerations subsequently progressing
      to two-timed splenic rupture that required surgery (absolute risk reduction,
      8.1%; 95% confidence interval, -7.6%-23.9%). With an observed prevalence of 54%
      for the presence of splenic injury, organ lacerations could be excluded more
      confidently using the linear probe (posttest probability, 16% vs. 36%).
      CONCLUSION: In slim patients, higher frequency linear ultrasound probes can
      provide therapy-relevant information on the integrity of splenic parenchyma after
      blunt abdominal trauma.

PMID- 11468465
TI  - Intra-abdominal pressure monitoring as a guideline in the nonoperative management
      of blunt hepatic trauma.
AB  - BACKGROUND: Nonoperative management has been validated as a standard of care for
      patients with blunt hepatic trauma. We herein study the correlation of intra
      abdominal pressure (IAP) and other clinical parameters to predict the failure of
      nonoperative management, and attempt to use IAP to determine further therapeutic
      options. METHODS: During a 9-month period, 25 hemodynamically stable patients
      sustaining grades III to V blunt hepatic injuries were prospectively studied.
      They were admitted to the intensive care unit for clinical reevaluation, and
      hemodynamic and IAP monitoring. If the patient developed an IAP greater than 25
      cm H(2)O, then an emergent laparotomy or laparoscopy was performed to achieve
      hemostasis and decompression of intra-abdominal hypertension (IAH). On the basis
      of an IAP of 25 cm H(2)O, the correlation between the IAP and an estimated amount
      of liver-related transfusion, the Pao(2)/Fio(2) ratio and peritoneal signs were
      analyzed. RESULTS: Of the 25 patients being studied, 20 (80%) had an IAP below 25
      cm H(2)O, 1 of whom was found to have a pelvic abscess from an amputated segment
      of liver. On the other hand, five other patients with an IAP greater than 25 cm
      H(2)O received decompression and laparoscopic examinations, and one needed an
      open hepatorrhaphy. In general, though, 19 patients (76%) were successfully
      treated without operation. All recovered well after different therapeutic
      regimens; however, two developed liver abscesses, for a morbidity rate of 8% (2
      of 25). This analysis revealed a strong association between the IAP value and the
      presence of peritoneal signs (Phi coefficient = 0.890, p < 0.001), but not in the
      estimated amount of liver-related transfusion and Pao(2)/Fio(2) ratio.
      CONCLUSION: This preliminary investigation suggests that IAH or abdominal
      compartment syndrome can develop while patients receive nonoperative management
      for grade III to V blunt hepatic injuries. There were no parameters that
      precisely reflected ongoing hepatic hemorrhage or predicted hemodynamic
      instability. Although the amount of hepatic hemorrhage was not accurately
      measured by the IAP, it could be reflected by an increased IAP. During
      nonoperative management, IAP monitoring may be a simple and objective guideline
      to suggest further intervention for patients with blunt hepatic trauma.
      Laparoscopic hepatic evaluation and abdominal decompression may be helpful in
      this situation.

PMID- 11468466
TI  - Sutureless liver repair and hemorrhage control using laser-mediated fusion of
      human albumin as a solder.
AB  - BACKGROUND: Major liver trauma has a high mortality because of immediate
      exsanguination and a delayed morbidity from septicemia, peritonitis, biliary
      fistulae, and delayed secondary hemorrhage. We evaluated laser soldering using
      liquid albumin for welding liver injuries. METHODS: Fourteen lacerations (6 x 2
      cm) and 13 nonanatomic resection injuries (raw surface, 8 x 2 cm) were repaired.
      An 805-nm laser was used to weld 53% liquid albumin-indocyanine green solder to
      the liver surface, reinforcing it by welding a free autologous omental scaffold.
      The animals were heparinized and hepatic inflow occlusion was used for vascular
      control. For both laceration and resection injuries, 16 soldering repairs were
      evaluated acutely at 3 hours. Eleven animals were evaluated chronically, two at 2
      weeks and nine at 4 weeks. RESULTS: All 27 laser mediated-liver repairs had
      minimal blood loss compared with the suture controls. No dehiscence, hemorrhage,
      or bile leakage was seen in any of the laser repairs after 3 hours. All 11
      chronic repairs healed without complication. CONCLUSION: This modality
      effectively seals the liver surface, joins lacerations with minimal thermal
      injury, and works independently of the patient's coagulation status.

PMID- 11468467
TI  - Use of V4R in patients who sustain blunt chest trauma.
AB  - OBJECTIVE: In blunt chest trauma, the right ventricle is more vulnerable than the
      left. The purpose of this study was to determine whether recording V4R in
      patients with blunt chest trauma would provide additional useful information to
      that already obtained from the standard 12-lead electrocardiogram (ECG). METHODS:
      Forty-five patients with blunt chest trauma and 40 unmatched control subjects
      without blunt chest trauma had standard 12-lead ECG and right precordial leads
      recorded. The ECGs were read blindly by three physicians. RESULTS: Patients with
      chest trauma were distinguishable from controls on the basis of the left-sided
      ECGs (odds ratio, 2.9; 95% confidence interval, 1.71-4.90). This was not the case
      using V4R (odds ratio, 1.23; 95% confidence interval, 0.59-2.0). CONCLUSION:
      Patients with a significant mechanism and physical findings of blunt chest trauma
      were more likely than controls to have an abnormal ECG. They were not more likely
      to have abnormalities in V4R. We recommend that a 12-lead ECG, but not V4R, be
      routinely obtained on these patients.

PMID- 11468469
TI  - A prospective evaluation of the clinical presentation of pediatric pelvic
      fractures.
AB  - BACKGROUND: We sought to describe pediatric, blunt trauma patients with pelvic
      fracture (PF) and to evaluate pelvis examination sensitivity and specificity.
      METHODS: We conducted a prospective study of blunt trauma patients at a Level I
      pediatric trauma center. A pediatric emergency medicine physician attempted to
      diagnose a PF, solely on the basis of the history and pelvis examination.
      Patients with blunt trauma but no pelvic fracture (NPF) were used as controls.
      RESULTS: We enrolled 140 patients (16 PF, 124 NPF), and no significant
      differences were found regarding median age, gender, injury mechanism, acuity,
      and medical outcome. Approximately 25% of PF patients had iliac-wing fractures;
      37%, single pelvic ring; 25%, double pelvic ring; and 13%, acetabular fractures.
      Eleven patients with PF had an abnormal pelvis examination (69% sensitivity),
      compared with six NPF patients (95% specificity, negative predictive value 0.91).
      CONCLUSION: Pediatric patients with PF have low mortality and few complex
      fractures. The pelvis examination appears to have both high specificity and
      negative predictive value.

PMID- 11468470
TI  - Child and family functioning 6 and 12 months after a serious pediatric fracture.
AB  - BACKGROUND: Previous findings indicate that pediatric fractures can have adverse
      consequences for child adjustment and family functioning immediately after
      injury. However, longer term effects of the fractures are unknown. The purposes
      of the present prospective study were to examine the child and family outcomes of
      pediatric traumatic fractures at 6 months and 1 year after injury, and to
      identify injury and treatment factors associated with these outcomes. METHODS: We
      evaluated 57 children 6 to 12 years of age with traumatic fractures requiring
      hospitalization. Using standardized measures and parent interview, we obtained
      measures of pre- and postinjury child and family functioning. RESULTS: Although
      outcomes were primarily positive at 1 year after injury, child functional
      limitations and family stress were observed up to 6 months after injury. Lower
      extremity fractures had a more negative impact on families across all three
      assessment points. Children with fracture interventions that involved prolonged
      immobilization had more functional limitations at 6 months than children who were
      ambulatory. Family burden was higher at 1 month for the immobilized children, but
      not at later follow-up. CONCLUSION: Some children and families experience adverse
      effects during the year after a serious pediatric fracture, especially if
      sustained in a lower extremity. Fracture stabilization that allows for greater
      ambulation may offer some benefits related to functional outcomes and family
      impact.

PMID- 11468471
TI  - The standard Gamma nail: a critical analysis of 1,000 cases.
AB  - BACKGROUND: The continuous increase in the number of fractures of the proximal
      femur is directly attributable to the worldwide increase in life expectancy. The
      standard version of the Gamma Interlocking-Nail (standard Gamma nail [SGN], 200
      mm length, 10-degree valgus curvature, two distal locking bolts) was designed
      because of the demands in orthopedic hip surgery to develop an implant stable
      enough to mobilize old patients as soon as possible to avoid further morbidity
      and mortality. METHODS: Between the years 1992 and 1998, 1,000 consecutive
      patients with peritrochanteric fractures were stabilized by using the SGN and
      included in this study. Special emphasis was given to the evaluation of the
      learning curve of the department of traumatology (not of single surgeons) and the
      influence of prognostic factors on the outcome of such operations. RESULTS: The
      results of this study show that increasing "department experience" resulted in a
      reduction of the intraoperative complication rate by a factor of 0.5 (p = 0.0001)
      per year. This means that even an inhomogeneous mass of 78 surgeons can lower the
      rate of intraoperative complications by 50% per year because of increased
      experience. The number of early postoperative complications annually decreased by
      a factor of 0.8 (p = 0.0042). CONCLUSION: Late postoperative complications
      correlate negatively with the patient's age (odds ratio, 0.9; p = 0.0001).

PMID- 11468472
TI  - The effect of intramedullary corticocancellous bone plug for hip
      hemiarthroplasty.
AB  - BACKGROUND: A prospective review was performed on 60 consecutive patients with
      hip hemiarthroplasty after femoral neck fractures. METHODS: Twenty-two patients
      underwent Austin Moore hemiarthroplasty with an intramedullary corticocancellous
      bone plug at the tip of the prosthesis (group A) and 38 patients underwent Austin
      Moore hemiarthroplasty alone (group B). The patients were evaluated clinically
      and radiographically at 3 and 6 months postoperatively and annually thereafter.
      RESULTS: There was no statistically significant difference in thigh pain score
      between the two groups. At 3- and 6-month follow-up, 88% and 83% of group A
      patients experienced no pain or mild thigh pain, compared with 72% and 76% in
      group B, respectively. The radiographs revealed more stem subsidence and calcar
      osteolysis in group B than in group A (p < 0.01 and p < 0.05, respectively).
      Furthermore, in both groups there was a correlation between calcar atrophy, stem
      subsidence, and early clinical thigh pain score (p < 0.05). CONCLUSION: Our data
      suggest that, whereas the radiologic findings in both groups may be related to
      thigh pain, they had little effect on the rate of femoral stem revision. We
      believe that the application of a corticocancellous bone plug in uncemented hip
      hemiarthroplasty for treatment of femoral neck fractures can decrease the
      incidence of early thigh pain in the first 6 months.

PMID- 11468473
TI  - Reduced serum total reductive capacity in lethal severe trauma.
AB  - BACKGROUND: Risk assessment is a prerequisite for effective treatment and triage
      in severe injury. A novel substrate-based assay to measure total reductive
      capacity (TORC) in serum was used to stratify risk of lethal outcome in severe
      trauma in a clinical trial. METHODS: Serum of patients with severe trauma (Injury
      Severity Score > 19) was obtained at the accident site, at admission, and at
      regular intervals thereafter. TORC was determined and correlated to outcome. The
      TORC assay uses thiol-labeled arachidonic acid as substrate from which free
      thiols are released by reductive amino acids and the specific activity of
      phospholipase A2. Free thiols are coupled to monochrombimone, and the resulting
      fluorescence is proportional to TORC. RESULTS: Eighteen patients with lethal
      severe trauma and 16 patients who survived were studied. Injury Severity Scores
      (lethal, 33 (29--43); survival, 31 (25--42); p = NS) and Polytrauma Scores
      (lethal, 25 [18--32]; survival, 26 [23--31], p = NS) were not significantly
      different. At the accident site, patients with a lethal course had significantly
      lower TORC than nonlethal cases (59.2 +/- 5.1 ng/mL vs. 89.5 +/- 6.7 ng/mL; p <
      0.001). Values at admission were similar (lethal, 51.2 +/- 7 ng/mL; survival,
      73.8 +/- 9 ng/mL; p < 0.01). At the accident site and at admission, TORC < 82.3
      ng/mL was prognostic of lethal outcome (sensitivity, 88%; specificity, 65%/73%
      and 69%, respectively, for admission). CONCLUSION: Serum reductive potential at
      the site of accident or at admission allows the stratification of trauma patients
      with respect to lethal outcome in severe trauma when severity scores fail to do
      so.

PMID- 11468474
TI  - Interleukin-10 and apoptotic death of circulating lymphocytes in
      surgical/anesthesia trauma.
AB  - OBJECTIVE: To examine the relationship between circulating interleukin-10 (IL-10)
      and the occurrence of lymphocyte apoptosis after surgical/anesthesia trauma.
      METHODS: Data were collected prospectively on 18 adult patients undergoing
      elective major surgery. Blood sampling for assessment of lymphocyte apoptosis and
      IL-10 levels was performed on the day before surgery (t(0)) and at 24 and 96
      hours after operation (t(1) and t(2), respectively). After lymphocyte isolation,
      quantification of apoptosis was made by staining apoptotic cells with 7-amino
      actinomycin D. Plasma IL-10 concentrations were measured using enzyme-linked
      immunosorbent assay. RESULTS: A significantly increased frequency of apoptotic
      CD4(+) and CD8(+) cells (p < 0.05) was observed at t1 measurement (8.10% +/-
      0.58% and 12.21% +/- 1.47% for CD4(+) and CD8(+), respectively) compared with
      preoperative values (1.53% +/- 0.38% and 1.32% +/- 0.45% for CD4(+) and CD8(+),
      respectively). Plasma IL-10 levels showed a significant elevation at both t(1)
      and t(2) times, peaking at t(1). At t(1), IL-10 levels were correlated with the
      frequency of CD4(+) and CD8(+) apoptotic lymphocytes (r = 0.78, p = 0.0005 for IL
      10 vs. apoptotic CD4(+); r = 0.71, p = 0.003 for IL-10 vs. apoptotic CD8(+)).
      CONCLUSION: Surgical trauma is associated with a significant but transient
      increase in lymphocyte commitment to apoptosis and IL-10 production. The exact
      relationship linking the overproduction of IL-10 with lymphocyte apoptosis after
      a surgical operation is still elusive and requires further investigation.

PMID- 11468475
TI  - Autofluorescence of skin burns detected by fiber-optic confocal imaging: evidence
      that cool water treatment limits progressive thermal damage in anesthetized
      hairless mice.
AB  - BACKGROUND: Although full-thickness burns present no difficulty to clinical
      judgment, accurate assessment of burn depth immediately after injury in partial
      thickness burns has always been difficult. METHODS: Thermal burns (applied by a 3
      mm-diameter brass rod heated to 50 degrees--80 degrees C for 20 seconds) were
      induced on the skin of anesthetized hairless mice. Anesthesia was maintained
      throughout all experiments. Both burns and normal skin were investigated
      noninvasively in vivo using fiber-optic confocal imaging (FOCI) microscopy
      (excitation, 488 nm; detection, 505 nm). RESULTS: Autofluorescence was detected
      in burned skin, and the depth of the autofluorescent region was found to
      correlate with the intensity of heat applied. Cool water treatment (for 20
      minutes immediately after burn induction) significantly reduced the progressive
      increase in autofluorescence in deeper layers of the skin over the 4-hour
      postburn observation period. Histology showed burn-associated changes at a lower
      temperature than that at which autofluorescence was first detected in vivo by
      FOCI. However, there was a good correlation (r = 0.78) between depth of damage
      revealed by FOCI compared with that by histology. CONCLUSION: These results
      suggest that FOCI may be used to provide an index of burn depth.

PMID- 11468476
TI  - Seat belt use before and after motor vehicle trauma.
AB  - BACKGROUND: Motor vehicle crashes cause significant morbidity and mortality
      annually. Seat belt use has partially been associated with a decreased risk of
      morbidity and mortality among those involved in motor vehicle crashes. Persons
      injured in motor vehicle crashes and not wearing seat belts have an increased
      risk of admission to trauma centers for motor vehicle crash-related injury. The
      purpose of this study was to measure changes in seat belt use after discharge
      among patients admitted to a Level I trauma center for injuries sustained in
      motor vehicle crashes. METHODS: Patients admitted to a Level I trauma center for
      injuries sustained in motor vehicle crashes during 1998 were eligible for
      participation. A telephone interview was conducted with a random sample of 136
      eligible patients regarding patterns of seat belt use before and after their
      collision. Demographic data and clinical characteristics were also collected. The
      frequency of seat belt use before and after crash involvement was compared for
      all patients and stratified by age, gender, race, and Injury Severity Score
      (ISS). RESULTS: Slightly over half (54%) of patients reported "always" wearing a
      seat belt before their collision compared with 85% afterward. Younger age groups,
      male subjects, and whites had the largest increases in the frequency of seat belt
      use after collision (45%, 37%, and 44% increases, respectively). With respect to
      injury severity, the largest increase in the frequency of seat belt use was among
      those with ISS of 15 to 25 (82% increase). Significant concordance between
      patient- and emergency medical service-reported use of seat belts was observed.
      Among subjects reported by emergency medical service personnel to have been
      restrained, nearly 90% reported belt use at the time of the telephone interview.
      The most frequently cited occasion for failure to use seat belts (30%) was when
      taking short trips. Other reported reasons were forgetting to fasten belts (29%),
      discomfort (10%), being in a rush (8%), riding in the back seat (4%), and that
      seat belts were unnecessary when riding with a good driver (3%). CONCLUSION:
      Involvement in a motor vehicle crash results in increased seat belt use.
      Prevention efforts should be directed toward those patients who report infrequent
      use. Patient "converts" to seat belt use after collisions may be useful in public
      awareness and prevention campaigns.

PMID- 11468477
TI  - Organ donation: a statewide survey of trauma surgeons.
AB  - PURPOSE: Organ procurement organizations (OPOs) operate under the premise that
      Americans would donate organs and/or tissue if placed in appropriate
      circumstances. This study evaluated opinions of Pennsylvania trauma surgeons
      regarding OPOs and organ donation. METHODS: Ninety-six Pennsylvania trauma
      surgeons were surveyed and descriptive results calculated. RESULTS: Ninety
      percent were familiar with criteria for organ donation, and about 76% would
      invoke their institution's brain death policy even if families did not desire to
      donate organs. A small portion did not routinely pronounce patients brain dead
      that met criteria. One fourth indicated trauma surgeons should have no role in
      requesting organs. A majority believed trauma surgeons should have a role in
      organ donation requests, either alone or with an OPO representative, and most
      indicated that they could influence a family's decision. CONCLUSION: Requestor
      attitude is important, and our results show an overall positive attitude toward
      donation and a solid level of knowledge regarding donor eligibility. Hospital
      development programs to improve donation consent should emphasize decoupling of
      brain death discussion and donation request, work to improve staff attitudes
      about approaching patients, and address donor eligibility criteria.

PMID- 11468478
TI  - Relationship between weather and seasonal factors and trauma admission volume at
      a Level I trauma center.
AB  - BACKGROUND: We sought to determine whether trauma patient admission volume to our
      Level I trauma center was correlated with observable weather or seasonal
      phenomena. METHODS: Trauma registry data and national weather service data for
      the period between September 1, 1992, and August 31, 1998, were combined into a
      common data set containing trauma admission data and weather data for each day.
      Sequential linear regression models were constructed to determine relationships
      between variables in the data set. RESULTS: There is a highly significant
      relationship (p < 0.00001) between maximum daily temperature and trauma
      admissions (R = 0.22). Rain is associated with a decrease in overall trauma
      volume. Rain had no effect on the number of admissions because of motor vehicle
      crash, however. Neither humidity nor snowfall affects trauma admission volume.
      Trauma admissions are significantly more frequent in July and August, and on
      Saturdays and Sundays (p < 0.05). Linear regression analysis identified maximum
      temperature, precipitation, day of week, and month as independent predictors of
      trauma admission volume (p < 0.001, R = 0.328). CONCLUSION: There is a
      significant relationship between weather and trauma center activity; temperature
      and precipitation are independently associated with trauma admission volume at
      our institution. Statistical models of trauma incidence should consider these
      phenomena. Evaluation of a larger, population-based data set is needed to confirm
      these relationships.

PMID- 11468479
TI  - Comparison of artificial intelligence techniques with UKTRISS for estimating
      probability of survival after trauma. UK Trauma and Injury Severity Score.
AB  - BACKGROUND: The development of TRISS was principally a search for variables that
      correlated with outcome. It is not known, however, if linear statistical models
      provide optimal results. Artificial intelligence techniques can answer this
      question and also determine the most important predictor variables. METHODS: An
      artificial neural network, using 16 anatomic and physiologic predictor variables,
      was compared with the latest United Kingdom version of TRISS model. RESULTS: Both
      methods were 89.6% correct, but TRISS was significantly better by the area under
      the receiver operating characteristic curve (0.941 vs. 0.921, p < 0.001). The
      artificial neural network, however, was better calibrated to the test data
      (Hosmer-Lemeshow statistic, 58.3 vs. 105.4). Head injury, age, and chest injury
      were the most important predictors by linear or nonlinear methods, whereas
      respiration rate, heart rate, and systolic blood pressure were underused.
      CONCLUSION: Prediction using linear statistics is adequate but not optimal. Only
      half the predictors have important predictive value, fewer still when using
      linear classification. The strongest predictors swamp any nonlinearity observed
      in other variables.

PMID- 11468480
TI  - Pathologic fracture of the scaphoid caused by intraosseous ganglion followed by
      regression after the healing of the fracture.

PMID- 11468481
TI  - False aneurysm appearing as delayed ulnar nerve palsy after "minor" penetrating
      trauma in the forearm.

PMID- 11468482
TI  - Neck abscess after blunt cervical trauma.

PMID- 11468483
TI  - Preoperative diagnosis of right hepatic vein injury by CT scan and venography.

PMID- 11468484
TI  - Traumatic hemobilia caused by false aneurysm of replaced right hepatic artery:
      case report and review.

PMID- 11468486
TI  - Complete trauma disruption of the left hepatic duct: endoscopic treatment after
      failure of surgical repair.

PMID- 11468487
TI  - Small bowel perforation after a quad cough maneuver.

PMID- 11468488
TI  - A chair leg as the rare cause of a transabdominal impalement with duodenal and
      pancreatic involvement.

PMID- 11468489
TI  - Use of esophageal tracheal combitube to control severe oronasal bleeding
      associated with craniofacial injury: case report.

PMID- 11468490
TI  - Intestinal Allis clamps as temporary vascular control for major retroperitoneal
      venous injury.

PMID- 11468491
TI  - Excessive use of normal saline in managing traumatized patients in shock: a
      preventable contributor to acidosis.

PMID- 11468492
TI  - Magnetic resonance venography to evaluate deep venous thrombosis in patients with
      pelvic and acetabular trauma.

PMID- 11468494
TI  - Assessing quality of life in dementia.

PMID- 11468495
TI  - Improving the primary care treatment of late life depression: progress and
      opportunities.

PMID- 11468496
TI  - EQ-5D in patients with dementia: an investigation of inter-rater agreement.
AB  - BACKGROUND: There are difficulties in obtaining health-related quality of life
      (HRQL) data from patients with dementia due to variation in their cognitive
      ability, degree of insight and capacity to make judgments. The use of proxies is
      one solution. OBJECTIVES: To examine the inter-rater agreement of patient and
      proxy completion of the EuroQol EQ-5D instrument (EQ-5D). RESEARCH DESIGN: The EQ
      5D instrument was completed separately by patients, their caregivers and a
      physician. Assessment of inter-rater agreement involved comparison of self
      completed (patient) and proxy-completed (caregiver and physician) responses for
      each dimension of EQ-5D, using a weighted kappa score. Three key hypotheses were
      tested. (1) Interrater agreement would be stronger between patient and caregiver
      than between patient and physician. (2) Interrater agreement would be stronger on
      the 'observable' and objective dimensions of EQ-5D. (3) Interrater agreement
      between patient and proxies would be stronger for patients with earlier dementia.
      SUBJECTS: The sample comprised 64 patients with a range of dementia severity.
      MEASURES: The EQ-5D health state classification system and visual analogue scale
      were used to assess HRQL. Global severity of dementia was determined using the
      Clinical Dementia Rating Scale. RESULTS: The principal finding of this study was
      that responses to EQ-5D questions were highly variable across the three raters
      such that none of the three hypotheses were strongly supported. CONCLUSIONS: The
      data provide some support for the use of EQ-5D when interviewer administered.
      However, there are serious concerns regarding the validity of patient self-rated
      HRQL data obtained in this study and uncertainty exists regarding who the
      appropriate proxy should be, as different groups of proxies provide different
      results. It was not clear whether caregivers or physicians represent better
      proxies. Further research should focus on the comparison of caregivers and
      physicians as proxies.

PMID- 11468497
TI  - Quality improvement research on late life depression in primary care.
AB  - BACKGROUND: Two million older Americans suffer from depression annually.
      Depression causes more functional impairment than many other common medical
      conditions and older adults have the highest rate of suicide in the United
      States. Although many of these patients fail to seek or fail to receive care for
      depression, the majority will be seen in primary care for the treatment of other
      conditions. OBJECTIVE: To review the health services research on quality
      improvement for late life depression. METHODS: Qualitative literature review.
      RESULTS: During the past 30 years, multiple educational and quality improvement
      interventions have been designed and tested to improve the recognition and
      treatment of depression in primary care settings. The findings from this large
      body of health services research suggest that: (1) the outcome of major
      depression in the usual care of primary care is typically poor; this is
      particularly true of late life depression; (2) informational support provided to
      primary care physicians is necessary but insufficient to improve the outcomes of
      late life depression in primary care; achieving guideline-level therapy requires
      the substantial participation of an informed and motivated patient working in
      concert with a health care team and health care system designed to care for
      chronic conditions; (3) up to 30% of older primary care patients will fail to
      respond to excellent guideline-level therapy provided in primary care; and (4)
      the latest quality improvement efforts focus not only on the clinical skills of
      primary care physicians, but also on patient's self-care and on innovative
      strategies to improve the system of care. CONCLUSIONS: Late life depression is
      often a chronic disease and outcomes research demonstrates that quality
      improvement efforts that focus resources on improving systems of care and the
      active participation of patients offer the best evidence of improved patient
      outcomes.

PMID- 11468498
TI  - Improving primary care for depression in late life: the design of a multicenter
      randomized trial.
AB  - BACKGROUND: Late life depression can be successfully treated with antidepressant
      medications or psychotherapy, but few depressed older adults receive effective
      treatment. RESEARCH DESIGN: A randomized controlled trial of a disease management
      program for late life depression. SUBJECTS: Approximately 1,750 older adults with
      major depression or dysthymia are recruited from seven national study sites.
      INTERVENTION: Half of the subjects are randomly assigned to a collaborative care
      program where a depression clinical specialist supervised by a psychiatrist and a
      primary care expert supports the patient's regular primary care provider to treat
      depression. Intervention services are provided for 12 months using antidepressant
      medications and Problem Solving Treatment in Primary Care according to a stepped
      care protocol that varies intervention intensity according to clinical needs. The
      other half of the subjects are assigned to care as usual. EVALUATION: Subjects
      are independently assessed at baseline, 3 months, 6 months, 12 months, 18 months,
      and 24 months. The evaluation assesses the incremental cost-effectiveness of the
      intervention compared with care as usual. Specific outcomes examined include care
      for depression, depressive symptoms, health-related quality of life, satisfaction
      with depression care, health care costs, patient time costs, market and nonmarket
      productivity, and household income. CONCLUSIONS: The study blends methods from
      health services and clinical research in an effort to protect internal validity
      while maximizing the generalizability of results to diverse health care systems.
      We hope that this study will show the cost-effectiveness of a new model of care
      for late life depression that can be applied in a range of primary care settings.

PMID- 11468499
TI  - PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory
      version 4.0 generic core scales in healthy and patient populations.
AB  - BACKGROUND: The PedsQL (Pediatric Quality of Life Inventory) (Children's Hospital
      and Health Center, San Diego, California) is a modular instrument for measuring
      health-related quality of life (HRQOL) in children and adolescents ages 2 to 18.
      The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and
      parent proxy-report scales developed as the generic core measure to be integrated
      with the PedsQL Disease-Specific Modules. The PedsQL 4.0 Generic Core Scales
      consist of 23 items applicable for healthy school and community populations, as
      well as pediatric populations with acute and chronic health conditions. METHODS:
      The 4 PedsQL 4.0 Generic Core Scales (Physical, Emotional, Social, School) were
      administered to 963 children and 1,629 parents (1,677 subjects accrued overall)
      recruited from pediatric health care settings. Item-level and scale-level
      measurement properties were computed. RESULTS: Internal consistency reliability
      for the Total Scale Score (alpha = 0.88 child, 0.90 parent report), Physical
      Health Summary Score (alpha = 0.80 child, 0.88 parent), and Psychosocial Health
      Summary Score (alpha = 0.83 child, 0.86 parent) were acceptable for group
      comparisons. Validity was demonstrated using the known-groups method,
      correlations with indicators of morbidity and illness burden, and factor
      analysis. The PedsQL distinguished between healthy children and pediatric
      patients with acute or chronic health conditions, was related to indicators of
      morbidity and illness burden, and displayed a factor-derived solution largely
      consistent with the a priori conceptually-derived scales. CONCLUSION: The results
      demonstrate the reliability and validity of the PedsQL 4.0 Generic Core Scales.
      The PedsQL 4.0 Generic Core Scales may be applicable in clinical trials,
      research, clinical practice, school health settings, and community populations.

PMID- 11468500
TI  - Activating patients for smoking cessation through physician autonomy support.
AB  - OBJECTIVE: Test whether physicians' counseling patients for smoking cessation
      with an autonomy supportive rather than controlling style would increase
      patients' active involvement in the counseling session and increase maintained
      abstinence. DESIGN: Randomized trial of 27 community-based physicians using two
      interview styles, with observer ratings of patient active involvement and
      assessments of patient smoking status at 6 months, 12 months, and 30 months.
      PATIENTS: Adult smokers: 336 recruited; 249 for final analyses. INTERVENTION:
      Physicians used an autonomy- supportive or controlling interpersonal style,
      randomly assigned within physician, to briefly counsel patients about smoking
      cessation, using the National Cancer Institute's 4-A's model. MEASUREMENT:
      Patient active involvement was rated from audio tapes of the interviews.
      Continuous abstinence came from self-reports at 6 months, 12 months, and 30
      months, CO validated at 6 months or 12 months and at 30 months. RESULTS:
      Physician style did not have a significant direct effect on smoking cessation but
      did significantly increase patient active involvement in the interview. Active
      involvement, in turn, increased smoking cessation. Structural equation modeling
      confirmed a theoretical model in which the intervention positively predicted
      patient active involvement after controlling for patient reports of wanting to
      stop smoking, and active involvement significantly predicted continuous
      abstinence after controlling for previous quit attempts. CONCLUSIONS: Although
      physicians' autonomy- supportive style while counseling smokers to quit did not
      have a direct effect on smoking cessation, it increased patients' active
      involvement in the counseling session which in turn increased continuous
      abstinence over 30 months. Further research should clarify the direct effects of
      physician interpersonal style on health outcomes.

PMID- 11468501
TI  - Assessing the clinical and economic burden of coronary artery disease: 1986-1998.
AB  - BACKGROUND: The acute phase of coronary artery disease (CAD) is dramatic and
      receives much attention because of its high mortality and associated treatment
      cost. However, the acute phase typically resolves within 30 days whereas CAD is a
      chronic disease, which most patients will live with for more than a decade. We
      compared the clinical and economic burden of CAD during the acute phase (first 30
      days) with that in the postacute phase (31st day through 10 years). METHODS: We
      included acute coronary syndrome (ACS) patients with significant CAD receiving an
      initial cardiac catheterization at Duke University Medical Center between 1986
      and 1997 with follow-up continuing through 1998. Inpatient medical costs were
      estimated from ACS clinical trial and economic study data. Costs were adjusted to
      1997 values and discounted at 3% per annum. RESULTS: Our study included 9,876 ACS
      patients (5,557 with an acute myocardial infarction [MI] and 4,319 with unstable
      angina [UA]). Acute MI patients had higher 30-day mortality than UA patients
      (5.6% vs. 2.3%, P <0.001). In addition, acute MI and UA patients had significant
      10-year unadjusted and adjusted survival differences (both P <0.001). For
      patients who survived to 30 days, there was no difference in 10-year survival
      between acute MI and UA patients before adjustment (P = 0.472). After adjustment,
      however, unstable angina patients who survived to 30 days had greater survival
      than myocardial infarction patients (P = 0.011). Mean 10-year discounted ACS
      inpatient medical costs were $45,253 ($23,510 acute phase and $21,819 postacute
      phase, P = 0.002). Ten year costs for unstable angina patients were $46,423
      ($21,824 acute phase and $24,599 postacute phase, P = 0.003); ten year costs for
      myocardial infarction patients were $44,663 ($24,823 acute phase and $19,840
      postacute phase, P <0.001). CONCLUSIONS: We found that the clinical and economic
      burden of CAD continues long after a patient's acute event has resolved and that
      postacute CAD cardiac event rates and inpatient medical costs may be higher than
      previously estimated. With much of all medical costs occurring in the postacute
      phase, the potential for effective secondary prevention therapies is substantial.

PMID- 11468502
TI  - Does providing consumer health information affect self-reported medical
      utilization? Evidence from the Healthwise Communities Project.
AB  - OBJECTIVE: To determine whether providing health information to residents of
      Boise ID had an effect on their self-reported medical utilization. RESEARCH
      DESIGN: The Healthwise Communities Project (HCP) evaluation followed a quasi
      experimental design. SUBJECTS: Random households in metropolitan zip codes were
      mailed questionnaires before and after the HCP. A total of 5,909 surveys were
      returned. MEASURES: The dependent variable was self-reported number of visits to
      the doctor in the past year. A difference-in-differences estimator was used to
      assess the intervention's community-level effect. We also assessed the
      intervention's effect on the variance of self-report utilization. RESULTS: Boise
      residents had a higher adjusted odds of entering care (OR = 1.27, 95% CI 0.88,
      1.85) and 0.1 more doctor visits compared with residents in the control cities;
      however, for both outcomes, the effects were small and not significant. Although
      the means changed little, the data suggest that the variance of utilization in
      Boise decreased. CONCLUSIONS: The HCP had a small effect on overall self-reported
      utilization. Although the findings were not statistically significant, a posthoc
      power analysis revealed that the study was underpowered to detect effects of this
      magnitude. It may be possible to achieve larger effects by enrolling motivated
      people into a clinical trial. However, these data suggest that population-based
      efforts to provide health information have a small effect on self-reported
      utilization.

PMID- 11468503
TI  - When parents are given greater access to health information, does it affect
      pediatric utilization?
AB  - OBJECTIVE: Most studies assessing the effects of consumer health information on
      medical utilization have used randomized controlled clinical trials with the
      chronically ill. In this paper, we analyze the effect of the Healthwise
      Communities Project, a natural experiment that provided free self-care resources,
      on reported pediatric utilization. RESEARCH DESIGN: Random household surveys were
      collected before and after the intervention in Boise, Idaho and in two control
      communities. SUBJECTS: A total of 5,909 surveys were completed, representing an
      overall response rate of 54%. Of these, 1,812 respondents were between 18 and 55
      years of age and had children under 18 years of age living in the home. All
      analyses were restricted to these 1,812 persons. MEASURES: Parents were asked how
      many times their children visited a physician in the last year. Responses were
      gathered with a categorical response scale, which was then transformed into a
      continuous variable (number of pediatric visits). RESULTS: The intervention was
      associated with a decrease in reported pediatric utilization rates. The decrease
      in visits ranged from -0.72 to -0.66 (P approximately 0.05), depending on the
      statistical model used. Further analyses of 423 families followed over time found
      a more modest decrease (-0.19) that was not statistically significant.
      CONCLUSIONS: This study found that increasing access to self-care books,
      telephone advice nurses, and Internet-based health information is associated with
      decreases in reported pediatric utilization. However, the significance of the
      results was sensitive to the statistical model. More research is needed to
      understand the average and marginal costs of providing health information to
      consumers.

PMID- 11468504
TI  - Identifying physicians likely to benefit from depression education: a challenge
      for health care organizations.
AB  - BACKGROUND: Few methods exist to identify physicians who might benefit from
      depression education. OBJECTIVES: To develop a measure of physicians' confidence
      or self-efficacy in caring for depressed patients and assess it's reliability and
      validity. RESEARCH DESIGN: A national sample of primary care physicians were
      surveyed and exploratory factor analysis (EFA) was used to identify factors
      underlying physicians' responses to 26 items. We named the factors, selected
      items with factor loadings > or = 0.50 for final scales, and tested a priori
      hypotheses about self-efficacy. SUBJECTS: 1) Random cross-sectional sample of
      family physicians, internists, obstetrician-gynecologists, and pediatricians (n =
      5,369) and 2) 49 general internists and family physicians participating in a
      prepost evaluation of a depression workshop. RESULTS: In the national sample,
      3,712 physicians were eligible and 2,104 responded. Forty-six percent were
      female, and 51% were family physicians and general internists. EFA identified 5
      factors, the first of which was called Self-Efficacy (4 items, alpha = 0.86).
      More family physicians (64%) had confidence (self-efficacy) in caring for
      depressed patients compared with general internists (33%), obstetrician
      gynecologists (16%), and pediatricians (6%) (P < 0.001). Few physicians intended
      to change their care of depressed patients (10%) or take CME on depression (24%).
      Of the 49 physicians attending a depression workshop, 76% reported high self
      efficacy after the workshop versus 50% before it (P = 0.013). CONCLUSIONS: This
      study supports the reliability and validity of the Self-Efficacy scale as one
      method to identify physicians who might benefit from interventions. New
      approaches are needed because physicians are unlikely to change.

PMID- 11468505
TI  - Use of SF-36 and SF-12 health status measures: a quantitative comparison for
      groups versus individual patients.
AB  - BACKGROUND: The extent to which SF-12 scores reflect SF-36 scores has not been
      well studied. OBJECTIVES: One purpose was to compare the sensitivity to change of
      the SF-36 Physical Function sub-score, and the Physical Component Summary Scores
      (PCS) of the SF-36 and SF-12 on patients with low back pain (LBP). A second
      purpose was to determine if the SF-12 could serve as a surrogate measure for the
      SF-36 when making decisions about individual patients. SUBJECTS: The sample
      consisted of 101 consecutive patients. MEASURES: SF-36 questionnaires were
      completed by patients at both initial and discharge examinations. SF-12 scores
      were calculated from the completed SF-36 questionnaires. Therapists' judgments of
      whether patients were judged to have returned to premorbid function served as the
      construct for meaningful clinical change. ANALYSIS: Receiver Operating
      Characteristic (ROC) curve analysis and repeated measures MANCOVA were used to
      assess sensitivity to change. Linear regression and 95% prediction bands
      described the extent to which SF-12 scores predict individual SF-36 scores.
      RESULTS: No significant differences were found between the ROC curve areas for
      the Physical Function sub-scale, the PCS-36 and PCS-12. No significant
      differences were found for the comparison of change scores between PF-36, PCS-36
      and PCS-12 scores. CONCLUSION: The findings suggest that Physical Function sub
      scores, SF-36 and SF-12 PCS scores are equally sensitive to change. SF-12 PCS
      scores do not adequately predict SF-36 PCS scores for individual patients. The
      PCS-12 should probably not be used to make judgments about the health status of
      individual patients with LBP.

PMID- 11468506
TI  - Regional variations in health status.
AB  - CONTEXT: Knowledge about variations in the health status of patients seeking
      primary care in different parts of the United States is limited. OBJECTIVE: To
      examine regional variations in the physical and mental health of patients
      receiving primary care in the largest integrated health care system in the United
      States which is operated by the Department of Veteran Affairs (VA). STUDY DESIGN
      AND SETTING: We performed a mailed, cross sectional survey of 54,844 patients who
      were enrolled in seven VA General Internal Medicine clinics. RESULTS: Among the
      30,690 patients who returned an initial set of screening questionnaires, the
      prevalence of common chronic conditions varied by as much as 60% among the seven
      clinics. Moreover, patients' general health (measured by the SF-36) also varied
      significantly in a pattern that mirrored the observed differences in the
      prevalence of chronic conditions. After adjustment for important comorbid
      illnesses and sociodemographic factors, geographic site accounted for a small
      percentage of the explained variance in patient assessed health status.
      CONCLUSIONS: The substantial differences in the health of patients enrolled in
      different VA primary clinics have important implications for the evaluation of
      clinical performance and health outcomes. Most of these differences can be
      attributed to sociodemographic and comorbid factors.

PMID- 11468507
TI  - Personal, organizational, and market level influences on physicians' practice
      patterns: results of a national survey of primary care physicians.
AB  - BACKGROUND: One of the principal tenets of managed care is that physicians'
      clinical decisions can be influenced both to improve the quality and consistency
      of care and to decrease health care expenditures. Medical decision making,
      however, remains a complex phenomenon and the most important determinants of
      physicians' approaches to clinical decision making remain poorly understood.
      OBJECTIVES: To determine how clinical decisions are associated with individual
      characteristics, practice setting and organizational characteristics, attributes
      of the patient population under care, and the market environment. RESEARCH
      DESIGN: Cross-sectional, nationally representative survey of patient-care
      physicians. SUBJECTS: Primary care physicians who provide direct patient care at
      least 20 hours per week. MEASURES: Proportion of physicians who would order a
      referral, diagnostic test, or treatment for 5 clinical scenarios thought to be
      representative of discretionary medical decisions. RESULTS: Responses were
      received from 4,825 primary care physicians who cared for adult patients
      (Response Rate 65%). The distribution of results for each of the five clinical
      scenarios demonstrates significant variability both within and between
      physicians. No evidence was seen of a consistent practice style across the
      vignettes (eg, "aggressive" or "conservative"). The organizational setting of
      practice was the most consistent predictor of behavior across all the clinical
      scenarios, with the exception of back pain, which was minimally related to any of
      the environmental factors. When compared to physicians in solo practice,
      physicians in all other practice settings were less likely to order a test or
      referral or pursue treatment. Practice involvement with managed care and measures
      of financial influences and administrative strategies associated with managed
      care were minimally and inconsistently associated with reported physician
      behaviors. CONCLUSIONS: The ability of managed care to improve the quality and
      consistency of care while also controlling the costs of care depends on its
      ability to influence medical decisions. Our findings generally demonstrate that
      managed care has a weak influence on discretionary medical decisions and that the
      influence of managed care pales in comparison to personal and practice setting
      influences.

PMID- 11468508
TI  - Comparison of the lectin-binding pattern in different human melanoma cell lines.
AB  - Glycosylation is generally altered in tumour cells in comparison with their
      normal counterparts. These alterations are thought to be important because they
      contribute to the abnormal behaviour of cancer cells. Therefore, we have
      comparatively analysed the glycoproteins in cell extracts from human melanoma
      (primary site--WM35; metastatic sites-- WM239, WM9 and A375) cell lines using
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis and lectin staining.
      The glycoprotein pattern of the WM35 line differed from that of the other cell
      lines in having less proteins that reacted with Sambucus nigra, Maackia amurensis
      and Phaseolus vulgaris agglutinins. A glycoprotein of about 70 kDa had a
      significantly increased reaction with Sambucus nigra agglutinin in all the cell
      lines from metastatic sites. In the WM9, WM239 and A375 cell lines, additional
      bands (160-100 kDa) were stained with Phaseolus vulgaris agglutinin, suggesting
      that cells from metastatic sites contain more glycoproteins with beta1-6
      branches. On the other hand, only minor changes in the reaction with Galanthus
      nivalis agglutinin, a mannose-specific lectin, were detected. Among the proteins
      showing different lectin staining, one, with an apparent molecular weight of 133
      kDa, was recognized by antibodies as N-cadherin. The present results suggest that
      in human melanoma the expression of branched and sialylated complex type N
      oligosaccharides consistently increased in cells from metastatic sites, and
      support the view that carbohydrates are associated with the acquisition of the
      metastatic potential of tumour cells.

PMID- 11468509
TI  - Impact of interferons on the expression of melanoma-associated antigens in
      melanoma short-term cell cultures.
AB  - Some immunotherapeutic approaches based on melanoma-associated antigens rely on
      in vitro cultivation of melanoma cells. A beneficial effect of interferons has
      been shown in melanoma. This study aimed to determine whether stimulation of
      patient-derived melanoma short-term cell cultures using interferon-alpha and 
      gamma changes the expression pattern of melanoma-associated antigens. Lymph node,
      skin and brain metastases were cultivated for up to 3 weeks and treated with
      interferon-alpha, interferon-gamma or mock stimulation. Expression of the
      melanoma-associated antigens MAGE-3, MelanA/MART-1 and tyrosinase was determined
      by flow cytometry and compared with the expression pattern of HLA class I
      molecules. We found consistently enhanced expression of HLA class I molecules,
      whereas the melanoma-associated antigens showed mixed responses, with moderate
      induction, suppression or no visible effect. The reaction to interferon
      stimulation was similar for all the antigens examined within a single melanoma
      cell culture. In contrast to the HLA class I molecules, which showed induced
      expression with interferon, the melanoma-associated antigens showed a varied
      response to interferon stimulation. Differential reaction to interferon
      stimulation is of importance to immunotherapeutic modalities and might influence
      progression of the disease. We therefore suggest that evaluation of variation in
      melanoma-associated antigen expression in the clinical setting may help to
      identify patients who would profit from adjuvant interferon therapy.

PMID- 11468510
TI  - A purified GM3 ganglioside conjugated vaccine induces specific, adjuvant
      dependent and non-transient antitumour activity against B16 mouse melanoma in
      vitro and in vivo.
AB  - The presence of substantial amounts of GM3 ganglioside on human melanomas and
      other tumours, together with its peculiar biological properties, makes this
      glycolipid a unique target for cancer immunotherapy. B16 mouse melanoma expresses
      GM3 and constitutes an appropriate model for the development of novel GM3-based
      vaccines. Recently, we hydrophobically incorporated purified GM3 into the outer
      membrane protein complex from Neisseria meningitidis to form very small size
      proteoliposomes (GM3/VSSP). We have examined the antitumour properties of
      GM3/VSSP vaccine and compared it with GM3 incorporated in very low density serum
      lipoproteins (GM3/VLDL). Immunization with four doses of GM3/VSSP vaccine (120
      microg of ganglioside) plus Freund's adjuvant or Montanide ISA 51 significantly
      increased the overall survival of mice inoculated in the subcutis with 103 B16-F1
      cells, whereas the GM3/VLDL immunogen was ineffective. The non-transient
      character of tumour protection was confirmed in animals surviving the first
      challenge and re-inoculated with 5 x 103 cells. GM3/VSSP vaccine also reduced the
      subcutaneous growth of highly aggressive B16-F10 cells. The importance of
      ganglioside structure in the tumour-protective effect of GM3/VSSP vaccine was
      confirmed using GM3 containing N-glycolylneuraminic acid, a ganglioside absent in
      melanoma cells. Immunostaining and enzyme-linked immunosorbent assay (ELISA)
      experiments showed a high specificity of immune sera against GM3 and the presence
      of all four IgG subclasses, with a preponderance of IgG2b and IgG3. In addition,
      a strong anti-B16 complement-mediated cytotoxicity was induced by vaccination
      with GM3/VSSP. The present data indicate the molecular specificity of GM3/VSSP
      vaccine as well as the adjuvant-dependent and non-transient character of tumour
      protection in the B16 mouse model. These findings suggest that an appropriate GM3
      vaccine may be capable of inducing prolonged tumour protection in melanoma
      patients.

PMID- 11468511
TI  - Suppression of macrophage nitric oxide production by melanoma: mediation by a
      melanoma-derived product.
AB  - The tumour-bearing state is known to induce immune dysfunction that contributes
      to increased infectious complications and tumour progression. However, the
      mechanisms underlying this immunosuppression remain unclear. This study
      investigated in a murine model the effects of melanoma growth on nitric oxide
      (NO) production by peritoneal macrophages in vivo and in vitro. B16 and K1735
      melanoma cells were inoculated subcutaneously into C57BL/6 and C3H/HeN mice,
      respectively. Stimulated NO production by elicited peritoneal macrophages was
      examined in control and melanoma- bearing mice. An in vitro system was
      established to assess the effects of co-culturing melanoma cells (B16 and K1735)
      or melanoma-conditioned medium with normal peritoneal macrophages on subsequent
      NO production. NO production was significantly suppressed in macrophages from
      melanoma-bearing mice. Co-culture of normal macrophages with melanoma cells in a
      transwell system or with melanoma-conditioned media in vitro reproduced the
      defects observed in vivo without affecting macrophage viability, pointing to a
      melanoma-derived product as the basis for the observed suppression of NO
      production. This inhibition required RNA and protein synthesis and was dose and
      time dependent. Using inhibition profiles and neutralizing antibodies, it was
      demonstrated that this melanoma inhibitory activity was distinct from known NO
      inhibitors. Preliminary characterization attributed this activity to a melanoma
      secreted protein moiety.

PMID- 11468512
TI  - Ultraviolet B-induced melanoma in Monodelphis domestica occurs in the absence of
      alterations in the structure or expression of the p53 gene.
AB  - Monodelphis domestica, a South American opossum, has been established as a
      mammalian model for sporadic ultraviolet radiation (UVR)-induced melanoma. Using
      this model system, we investigated the role of changes in the p53 gene in the
      development of cutaneous melanocyte-derived lesions. Cutaneous melanocytic
      hyperplasias, benign melanomas and metastatic primary melanomas, plus affected
      lymph nodes and visceral organs, were screened for mutations in the Monodelphis
      p53 gene by single-strand conformation polymorphism analysis and direct
      sequencing. With the exception of a silent point mutation found in a single
      benign melanocytic hyperplasia sample, no p53 mutations were detected.
      Furthermore, a relative quantitative reverse transcriptase-polymerase chain
      reaction approach was used to analyse p53 gene expression at different stages of
      primary melanoma progression and revealed no substantial changes in p53 mRNA
      levels. These results suggest that, as in humans, UVR-induced melanoma in the
      Monodelphis model is initiated and progresses on the basis of predominantly p53
      independent molecular pathways.

PMID- 11468513
TI  - Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene:
      results from a murine tumour model.
AB  - An empirically established chemoimmunotherapy that combines the epifocal
      application of the contact sensitizer dinitrochlorobenzene (DNCB) to cutaneous
      metastases with the systemic administration of dacarbazine (DTIC) yields high
      response rates and results in prolonged survival. However, despite the fact that
      this therapy has been in clinical use for several years, the mode of action still
      remains elusive. In order to overcome this limitation we established a murine
      model system. B16 melanoma cells were implanted subcutaneously in syngeneic
      C57BL/6 mice and treatment was started 7 days after. In a first set of
      experiments mice received intraperitoneal injections of DTIC followed by epifocal
      applications of DNCB 24 h later. Treatment significantly decreased tumour growth.
      In contrast, no significant effect was induced by DTIC or DNCB alone. Using this
      regimen, with varying doses of either DTIC or DNCB, we demonstrated that the
      therapeutic effect is dose dependent. Furthermore, the treatment of subcutaneous
      tumours with DTIC and DNCB influenced the course of visceral metastases: the
      growth of pulmonary metastases was significantly inhibited if subcutaneous
      tumours were treated as described. In conclusion, we have established a model
      system that seems to be appropriate for both the optimization of this therapeutic
      regimen and the characterization of effector mechanisms.

PMID- 11468514
TI  - Prognostic factors in uveal melanoma.
AB  - Uveal melanoma is the most common primary intraocular malignant tumour, with an
      annual incidence of approximately six cases per million per year. Approximately
      40% of patients with posterior uveal melanoma develop metastatic melanoma to the
      liver within 10 years after initial diagnosis. Despite high accuracy of diagnosis
      and availability of various methods of treatment; the mortality due to uveal
      melanoma has remained unchanged. The prognosis in uveal melanoma depends on
      clinical, histopathological and cytological factors. Clinical factors that relate
      to prognosis include location, size, and configuration of the tumour. Uveal
      melanoma can arise in the iris, the ciliary body or the choroid. Iris melanomas
      have the best prognosis and ciliary body melanomas have the worst prognosis.
      Based on retrospective studies, the mortality rates for uveal melanoma for
      comparable sized tumours treated by enucleation or other globe conserving methods
      such as radiotherapy appear to be similar. Histopathological factors such as cell
      type, mitotic activity, microcirculation architecture, tumour-infiltrating
      lymphocytes and the presence of extrascleral extension are also significant
      predictors of survival. More recently, cytological factors such as cell
      proliferation, cytogenic, and molecular genetic prognostic markers have been
      identified with the hope of detecting high risk cases for adjuvant systemic
      immune therapy or chemotherapy. At present, the role of these therapeutic methods
      is not clearly established.

PMID- 11468515
TI  - Expression of integrins, degradative enzymes and their inhibitors in uveal
      melanoma: differences between in vitro and in vivo expression.
AB  - Posterior uveal melanoma is the most common intraocular malignancy in adults.
      Metastasis occurs in approximately 40% of all cases and spread is primarily to
      the liver. Once secondary hepatic disease has developed the prognosis is poor.
      Metastasis involves a series of adhesion and de-adhesion events, coupled with
      regulated tissue degradation to facilitate tumour cell invasion and spread to
      both local and distant sites. These processes are assisted by the expression of
      integrins and degradative enzymes by both tumour and host cells. Using a series
      of 10 uveal melanomas, we investigated the expression of a panel of integrins,
      degradative enzymes and their inhibitors that have been shown to be associated
      with metastasis. In addition, we undertook to establish if there might be
      differential expression in response to growth under artificial conditions. All
      the tumours expressed matrix metalloproteinases (MMP)-2 and-9, tissue inhibitor
      of metalloproteases (TIMP)-2, urokinase plasminogen activator (u-PA), plasminogen
      activator inhibitor (PAI)-1 and PAI-2. Differences in the expression of the
      integrins alpha1beta1, alpha2beta1 and alpha6beta1 were observed; in particular,
      these differences appeared to relate to expression as a consequence of growth in
      culture. In summary, uveal melanoma cells express both degradative enzymes and
      their respective inhibitors, which are important in metastasis. It would appear
      that differential expression of integrins is present, probably as a response to
      in vitro stimulation.

PMID- 11468516
TI  - Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma is associated
      with progression to metastatic disease.
AB  - In order to determine the effects of the loss or reduced expression of molecules
      associated with antigen presentation (transporter associated with antigen
      presentation [TAP]-1, TAP-2, low molecular weight protein [LMP]-2 and LMP-7), we
      examined the expression of these molecules in primary uveal melanoma lesions.
      Paraffin-embedded sections from 29 primary uveal melanoma lesions were analysed
      for expression of TAP-1, TAP-2, LMP-2 and LMP-7 using specific primary antibodies
      followed by a three-stage immunoperoxidase technique. Microscopic examination was
      undertaken to determine differences in expression of these molecules on the
      tumour and the surrounding stroma. Overall, 72% (21 out of 29) of the tumours
      showed some loss or reduced expression of TAP-1, TAP-2, LMP-2 and/or LMP-7.
      Statistical analysis of these results showed that progression to metastatic
      disease was strongly associated with reduced expression of TAP-1 (P < 0.05) and
      TAP-2 (P < 0.01), taking patient age, tumour site and histology into account. We
      conclude that the reduced expression of molecules important in eliciting an
      immune response, such as TAP-1 and TAP-2, may facilitate the metastatic spread of
      uveal melanoma lesions and may have important implications for prospective
      immunotherapy.

PMID- 11468517
TI  - Instability at sequence repeats in melanocytic tumours.
AB  - To obtain information on the prevalence of microsatellite mutations in melanomas,
      we analysed the status of 14 repetitive loci characterized by structurally
      different non-coding and coding sequence repeats in a panel of 34 primary
      melanocytic tumours and in lymph node metastases matched to 13 cases. Instability
      at one or more of the non-coding dinucleotide repeats D2S123, D3S1611, D5S107 and
      D18S34 was detected in ten out of the 34 primary tumours (29%) and in ten of the
      13 metastases (77%). There was no instability at the non-coding mononucleotide
      repeats BAT25, BAT26 and APDelta3 or at the coding mononucleotide runs within the
      TGFbetaRII, IGFIIR, BAX, hMSH3 and hMSH6 genes. A five-repeats expansion of the
      coding E2F4(CAG)n run was found in the only malignant melanoma of soft parts
      examined, which also showed instability at two dinucleotide loci, and in a
      superficial spreading melanoma, which was stable at the mononucleotide and
      dinucleotide repeats but was the only tumour that manifested instability at the
      SCA1(CAG)n repeat. The absence of mutations at mononucleotide tracts indicates
      that, in the malignant melanomas tested, microsatellite instability was not
      associated with the microsatellite mutator phenotype characteristic of mismatch
      repair-deficient tumours. On the other hand, our results confirm that
      microsatellite instability at dinucleotide repeats increases with melanoma
      progression, and indicate that expansions of triplet repeats may occur in
      melanocytic tumours.

PMID- 11468518
TI  - Are responses to therapy of metastasized malignant melanoma reflected by
      decreasing serum values of S100beta or melanoma inhibitory activity (MIA)?
AB  - In metastatic melanoma S100beta as well as melanoma inhibitory activity (MIA) are
      elevated in the serum in the majority of patients. Elevation has been found to
      correlate with shorter survival, and changes in these parameters in the serum
      during therapy were recently reported to predict therapeutic outcome in advanced
      disease. However, the value of these markers with respect to other possible
      markers by multivariate analysis has not yet been proven for individual patients.
      In this prospective study, S100beta and MIA were measured in the serum of 67
      consecutive patients before and following treatment. Analysing both the
      sensitivity and the specificity of the serum parameters by the areas under the
      receiver operating characteristics (ROC) curves, decreases in S100beta and MIA
      during therapy were associated with response to therapy, while increases
      indicated progressive disease. Unexpectedly, the individual diagnostic value of
      changes in tumour markers during therapy was not superior to one-point
      measurements at restaging. Moreover, S100beta and MIA were not superior to the
      conventional parameters lactate dehydrogenase and C-reactive protein (CRP) on
      multiple logistic regression analysis. Applying classification and regression
      trees (CARTs), one-point measurements of CRP was shown to be the most relevant
      overall parameter.

PMID- 11468519
TI  - FDG-PET in the detection of gastrointestinal metastases in melanoma.
AB  - We report six cases of malignant melanoma metastatic to the small bowel in which
      the information obtained from fluorodeoxyglucose positron emission tomography
      (FDG-PET) contributed significantly to the management of the patients. In each of
      these cases the conventional diagnostic work-up missed findings that were
      important for treatment planning. We conclude that FDG-PET is a valuable modality
      in melanoma patients with suspected gastrointestinal involvement. It is also a
      sensitive technique for the diagnosis of other intra-abdominal as well as extra
      abdominal metastases.

PMID- 11468520
TI  - No indication for performing sentinel node biopsy in melanoma patients with a
      Breslow thickness of less than 0.9 mm.
AB  - In thin melanomas, the involvement of regional nodes is very uncommon. Recent
      sentinel node (SN) studies have confirmed the absence of positive regional lymph
      nodes in melanomas < 0.76 mm and a 5% positivity in melanomas between 1.0 and
      1.99 mm. The chance of regional lymph node involvement - and therefore whether it
      is relevant to perform the SN procedure - seems to depend on the Breslow
      thickness of the primary tumour. However, a Breslow thickness cut-off point has
      not yet been established. We evaluated a melanoma population that had undergone
      an SN procedure to determine this point, so that the procedure can be restricted
      to a smaller group of patients in future. In a total of 348 patients with proven
      American Joint Committee on Cancer (AJCC) stages I or II cutaneous melanoma with
      a Breslow thickness > or = 0.5 mm the triple technique was used, consisting of
      preoperative visualization of the lymph channels from the initial site of the
      melanoma towards the SN by (dynamic) lymphoscintigraphy, intraoperative
      visualization of those particular lymph channels and nodes with blue dye, and a
      gamma probe to measure accumulated radioactivity in radiolabelled lymph nodes. In
      melanomas thinner than 0.90 mm, no positive SN was found (95% confidence interval
      0-5%). This group consisted of 75 patients (22%), with a median follow-up of 31
      months. Our data suggest that this procedure need no longer be indicated for
      almost a quarter of the patient population, because the cut-off point for nodal
      involvement appears to be a Breslow thickness of 0.90 mm.

PMID- 11468521
TI  - A phase II study of high dose tamoxifen and weekly cisplatin in patients with
      metastatic melanoma.
AB  - We have previously demonstrated that the combination of tamoxifen and cisplatin
      has activity in patients with metastatic melanoma. In vitro studies have
      demonstrated that tamoxifen and cisplatin exhibit cytotoxic synergy in human
      melanoma cells and that this interaction is dependent on a tamoxifen effect. The
      mechanism of this effect is currently under investigation in in vitro studies. In
      an attempt to improve the complete response rate of this regimen, we initiated a
      phase II trial to determine the effect of the use of high dose tamoxifen and
      weekly cisplatin on the complete response rate, disease-free survival and overall
      survival. Tamoxifen was started on day 1 initially at a dose of 240 mg/day and
      continued until the patient was taken off treatment. This dose was subsequently
      lowered to 200 mg/day. Cisplatin (80 mg/m2) was begun on day 2 and repeated
      weekly for a total of 3 weeks. During week 4, the patient was not treated with
      cisplatin but was evaluated for response. If disease stabilization or regression
      was documented, the patient received a second 3 week cycle of cisplatin and was
      then re-evaluated for response. Patients with progressive disease at any
      evaluation were removed from the study. In 28 consecutive patients, the overall
      response rate was 32% (95% confidence interval 15.88-52.35%). One patient
      achieved a complete remission that lasted 22 months. All other responses were
      partial in nature. Toxicity was primarily nausea and vomiting. Two patients
      developed grade 2 renal toxicity. There were no episodes of deep venous
      thrombosis. This phase II study demonstrates that this combination has modest
      activity in patients with metastatic melanoma. However, this study failed to
      confirm our hypothesis that high dose tamoxifen would increase the complete
      response rate of this combination. While this combination has activity, the
      overall response rate is not significantly better that that observed with the
      original Dartmouth regimen and the toxicity is substantial. We do not recommend
      this dose and schedule for routine clinical use.

PMID- 11468522
TI  - Prognostic factors in therapeutic lymphadenectomy in melanoma.

PMID- 11468524
TI  - Karl Landsteiner: a hundred years later.

PMID- 11468525
TI  - Skin allograft rejection by stable hematopoietic chimeras that accept organ
      allografts sill is an enigma.

PMID- 11468526
TI  - Current approaches to increase organ donation: a brief review from the United
      Kingdom perspective.

PMID- 11468527
TI  - Another nail in the coffin for conventional immunosuppressive regimens with the
      advent of tolerizing regimens.

PMID- 11468528
TI  - Promising early outcomes with a novel, complete steroid avoidance
      immunosuppression protocol in pediatric renal transplantation.
AB  - BACKGROUND: Corticosteroids have been a cornerstone of immunosuppression for four
      decades despite their adverse side effects. Past attempts at steroid withdrawal
      in pediatric renal transplantation have had little success. This study tests the
      hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid
      dependency for suppression of the immune response with its accompanying risk of
      acute rejection on steroid withdrawal. METHODS: An open labeled prospective study
      of complete steroid avoidance immunosuppressive protocol was undertaken in 10
      unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first
      renal allografts. Steroids were substituted with extended daclizumab use, in
      combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were
      performed in the steroid-free group at 0, 1, 3, 6, and 12 months
      posttransplantation. Clinical outcomes were compared to a steroid-based group of
      37 matched historical controls. RESULTS: Graft and patient survival was 100% in
      both groups. Clinical acute rejection was absent in the steroid-free group at a
      mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the
      steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12
      months) revealed only two instances of mild (Banff 1A) subclinical rejection
      (reversed by only a nominal increase in immunosuppression) and no chronic
      rejection. At 6 months the steroid-free group had no hypertension requiring
      treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body
      disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height
      Z scores trended better in the steroid-free group. In the steroid-free group, one
      patient had cytomegalovirus disease at 1 month and three had easily treated
      herpes simplex stomatitis, but with no significant increase in bacterial
      infections or rehospitalizations over the steroid-based group. The steroid-free
      group was more anemic early posttransplantation (P=0.004), suggesting an early
      role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by
      6 months. CONCLUSIONS: Complete steroid-free immunosuppression is efficacious and
      safe in this selected group of children with no early clinical acute rejection
      episodes. This protocol avoids the morbid side effects of steroids without
      increasing infection, and may play a future critical role in avoiding
      noncompliance, although optimizing renal function and growth.

PMID- 11468529
TI  - Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to
      university of wisconsin solution on reperfusion injury in liver transplantation.
AB  - BACKGROUND: Activation of p38 mitogen-activated protein kinase (MAPK) plays an
      important role in the development of ischemia/reperfusion injury in nonhepatic
      organs, such as the heart. However, the role of p38 MAPK activation in the liver
      is unclear. We examined the effects of FR167653, a novel p38 MAPK inhibitor, as
      an additive to University of Wisconsin (UW) solution in rat liver
      transplantation. METHODS: Rat orthotopic liver transplantation was performed
      after 30 hr of cold storage using UW solution with or without FR167653. Ten-day
      survival rates, serum alanine aminotransferase (ALT) and lactate dehydrogenase
      (LDH) levels, liver tissue blood flow, histological findings, and activities of
      p38 MAPK and p46/p54 c-Jun N-terminal kinase (JNK) in liver grafts were
      evaluated. RESULTS: The addition of FR167653 significantly increased animal
      survival rates. FR167653 significantly suppressed serum ALT and LDH levels and
      improved liver tissue blood flow after transplantation. FR167653 also ameliorated
      histological damage to the liver graft. Neither p38 MAPK nor p46/p54 JNKs was
      activated during cold storage, whereas both were markedly activated within 30 min
      of reperfusion and remained activated until 60 min after reperfusion. FR167653
      inhibited the activation of p38 MAPK both 30 and 60 min after reperfusion, but it
      did not affect the activation of p46/p54 JNKs. CONCLUSIONS: The addition of
      FR167653 to UW solution improved liver graft viability and animal survival rates
      associated with the inhibition of p38 MAPK activation. These results suggest that
      inhibiting the activation of p38 MAPK may attenuate ischemia/reperfusion injury
      in liver transplantation.

PMID- 11468530
TI  - Pyruvate inhibits hepatic ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury is a limiting factor in liver
      transplantation. We have recently shown that pyruvate (PY) inhibits intestinal
      and renal I/R injury. This study aims to evaluate the protective effect of PY on
      hepatic I/R injury. METHODS: ACI rats were treated with PY, whereas control
      animals received placebo. Rats were killed after 60 min of partial hepatic
      ischemia and after 2, 6, 24, and 48 hr of reperfusion. For each time point, serum
      aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase
      were measured, and liver biopsy specimens were obtained to evaluate morphology,
      DNA fragmentation, and apoptosis (terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-biotin nick end labeling). RESULTS: The survival rate
      48 hr after I/R was 83% in the control group, and 100% in the PY-treated group
      (P>0.05). Increased enzymatic levels and histologic findings showed increased
      liver damage in the untreated group compared with PY. In control rats, apoptosis
      was enhanced after 1 hr of ischemia and peaked after 2 hr of reperfusion, to
      decrease gradually 48 hr after reperfusion; in the PY group apoptosis was delayed
      and reduced. After 1 hr of ischemia, the number of apoptotic nuclei was
      significantly increased in control livers compared with normal preischemic
      livers, whereas the number was significantly reduced by PY. After 2 hr of
      reperfusion, the maximum number of apoptotic cells was observed, whereas PY
      significantly reduced the amount of apoptotic cells (P<0.05). Apoptosis was
      delayed in PY-treated livers to 6 hr after reperfusion, peaking at a
      significantly lower count compared with placebo-treated controls (P<0.05).
      CONCLUSION: These data indicate that PY has a protective effect on I/R injury of
      the liver.

PMID- 11468531
TI  - Early induction of platelet-derived growth factor ligands and receptors in acute
      rat renal allograft rejection.
AB  - BACKGROUND: Acute rejection is the single most important risk factor for the
      development of subsequent chronic rejection. Platelet-derived growth factor
      (PDGF) is a major mitogen that mediates mesenchymal cell proliferation in chronic
      rejection. Therefore, we investigated whether PDGF ligands and receptors are
      induced during acute renal allograft rejection in rat. METHODS: Kidney
      transplantations were performed from Dark Agouti (DA) to Wistar-Furth (WF) rats,
      and syngenic controls were performed from DA to DA rats. Allografts were
      immunosuppressed with cyclosporine (CsA) 1.5 mg/kg/d subcutaneously or left
      untreated. Grafts were harvested at 1, 3, 5, and 7 days for histology and
      immunohistochemistry. RESULTS: In syngenic grafts, no histological signs of acute
      rejection were seen and the expression of PDGF ligands and receptors remained
      almost nonexistent. In nontreated allografts, intense rejection resulted in graft
      necrosis in 7 days. Acute rejection was associated with the induction of all PDGF
      ligands and receptors (P<0.05 compared to syngenic controls). The expression of
      PDGF ligands and receptors was located mainly to graft-infiltrating macrophages
      but also to capillary endothelium and arteriolar smooth muscle cells. CsA
      significantly ameliorated acute rejection but failed to inhibit the induction of
      PDGF and its receptors in CsA-treated allografts. CONCLUSIONS: Our results
      demonstrate that PDGF ligands and receptors are induced during acute rejection.
      PDGF may be induced directly as a reparative response to graft injury in acute
      rejection or indirectly by various inflammatory mediators released by graft
      infiltrating inflammatory cells. This study indicates that PDGF ligands and
      receptors are already induced in acute rejection, which suggests a link between
      acute rejection and the subsequent development of chronic rejection.

PMID- 11468532
TI  - Combined immunosuppression of mycophenolate mofetil and FK506 for myoblast
      transplantation in mdx mice.
AB  - BACKGROUND: Overcoming adverse effects of immunosuppressors can be achieved by
      combining different drugs, thus allowing a dosage reduction. Myoblast
      transplantation is a potential therapy for Duchenne muscular dystrophy. Our
      research group previously established that FK506 (tacrolimus) is an effective
      immunosuppressive drug for myoblast transplantation in mice and monkeys. METHODS:
      In the present study, a reduced dose of FK506 at 1.0 mg/kg/day was used in
      combination with mycophenolate mofetil (MMF; 80 mg/kg/day) as an
      immunosuppressive protocol for myoblast transplantation. Graft success was
      evaluated by quantifying the number of dystrophin-positive fibers per muscle
      section that were injected with normal cells. RESULTS: MMF used alone could not
      prevent immune rejection of the transplanted myoblasts. MMF given in combination
      with FK506 immediately after transplantation reduced the success of myoblast
      transplantation by about 50%. A low dose of FK506 combined with MMF after the
      establishment of the graft (3 weeks) maintained graft success and controlled
      immune infiltration compared with a low dose of FK506 alone. However, lymphocyte
      infiltration was observed at longer term using a low dose of FK506 combined with
      MMF. CONCLUSIONS: The diminution of graft success when combining FK506 and MMF by
      the time of myoblast transplantation could be attributed to the inhibition of
      myoblast fusion by MMF. The use of MMF and FK506 after the establishment of the
      graft did not reduce graft success, however, this combination was not effective
      at controlling long-term immune rejection in comparison with the optimal dose of
      FK506 alone.

PMID- 11468533
TI  - A short course of methylprednisolone immunosuppression inhibits both rejection
      and spontaneous acceptance of rat liver allografts.
AB  - BACKGROUND: The effects of immunosuppressive drugs on transplant tolerance have
      not been extensively studied, although their effect on rejection is well
      established. METHODS: We examined the effects of a short course of treatment with
      the immunosuppressive drug methylprednisolone (MP) on the survival of PVG liver
      allografts in Dark Agouti (DA) recipients that accepted the livers and in Lewis
      recipients that rejected the livers. Infiltration of liver allografts was
      examined by immunohistochemical staining of liver sections, and apoptosis was
      measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling.
      RESULTS: A 5-day course of MP (days 0 to 4) led to rejection of four of six
      livers (mean survival time [MST] 99 days) in DA recipients compared with long
      term survival (MST >100 days) in untreated animals. Delayed administration of MP
      (days 3 to 7) exacerbated rejection in DA recipients, and all eight animals
      rejected the graft (MST 68.5 days). Treatment of Lewis recipients with MP did not
      significantly prolong survival when administered from days 0 to 4 (MST 13 days),
      although delay of administration improved the outcome. Treatment from days 3 to 7
      resulted in an MST of 21 days, whereas treatment from days 7 to 11 resulted in an
      MST of 41.5 days. MP treatment from day 3 to day 7 reduced T cells and
      interleukin 2 receptor-expressing cells but increased the numbers of apoptotic
      cells infiltrating both DA and Lewis strain allografts. CONCLUSIONS: These
      results show that immunosuppression with MP inhibits both spontaneous tolerance
      and rejection of liver allografts in a rat model and question the efficacy of
      administering MP to all liver allograft recipients from the time of
      transplantation.

PMID- 11468534
TI  - Predictors of organ donation registration among Dutch adolescents.
AB  - BACKGROUND: In 1998, a new organ donor registration scheme was implemented in the
      Netherlands in order to increase the number of potential donors and to facilitate
      decisions and procedures concerning organ donation. However, registration rate
      and registration choices failed to meet the expectations. METHODS: A cross
      sectional survey among a random sample of 1,731 Dutch adolescents of 18 and 19
      years was conducted to study potential determinants of organ donor registration
      choices. RESULTS: Almost one fifth of the adolescents indicated that they did not
      return their organ donation registration form. Among subjects who registered, 57%
      were willing to donate their organs or tissues posthumously. More positive social
      influences, fewer negative outcome beliefs, and a low level of organ donation
      anxiety were significant predictors of returning a completed registration form
      and registration as an organ donor. In addition, religion was a significant
      predictor of returning a completed registration form, and positive outcome
      beliefs contributed to the prediction of registration as an organ donor.
      CONCLUSIONS: The results give clear suggestions for tailoring organ donation
      registration interventions to specific characteristics, beliefs, and
      misconceptions of adolescents. The results also suggest that it is important to
      encourage adolescents to discuss issues related to organ donation with their
      parents and friends in order to increase donor registration.

PMID- 11468535
TI  - Outcome of cadaveric renal transplant patients treated for 10 years with
      cyclosporine: is chronic allograft nephropathy the major cause of late graft
      loss?
AB  - BACKGROUND: The introduction of cyclosporine (CsA) has improved the short-term
      outcome of renal transplantation, but its effect on the long-term survival is not
      well known. METHODS: We analyzed 128 cadaveric first renal transplant recipients
      with CsA and prednisone as basal immunosuppression followed for at least 10
      years, and we have compared them with a group of 185 historical patients treated
      with azathioprine (Aza) and prednisone. RESULTS: The 1-year graft survival was
      83% in the CsA-treated patients and 68% in the Aza-treated patients (P<0.025),
      and the differences were significant for 3 years. Acute rejection accounted for
      the 10.9% of losses in CsA-treated patients and for 23.8% of losses in Aza
      treated patients (P=0.046). Chronic allograft nephropathy was the cause of graft
      losses in 40.6% and 16.8% of cases (P=0.008). Patient survival at 5 years was 88%
      in CsA-treated patients and 79% in the Aza-treated patients (P<0.025). When
      analyzing the data of the 64 CsA-treated patients and the 84 Aza-treated patients
      with one functioning graft at 10 years, mean serum creatinine values were
      significantly higher in the CsA-treated patients at all time points but the
      increases were not significantly different. At 10 years, mean blood pressure was
      higher (P=0.002), and hypercholesterolemia (P=0.011) and hyperuricemia (P=0.000)
      were more prevalent in the CsA-treated patients. CONCLUSIONS: CsA resulted in a
      better short-time patient and graft survival that was not maintained in the long
      term outcome. Chronic allograft nephropathy was the leading cause of graft loss
      in CsA-treated patients. Graft function was poorer in the CsA-treated patients,
      but its decline was similar in the two groups.

PMID- 11468536
TI  - Dose optimization of mycophenolate mofetil when administered with a low dose of
      tacrolimus in cadaveric renal transplant recipients.
AB  - BACKGROUND: Supplementation of immunosuppressive therapy with mycophenolate
      mofetil (MMF) has been found to reduce the rate of acute rejection in renal
      transplantation. We report a dose-finding study for MMF when administered in
      combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric
      renal transplant recipients. METHODS: Two hundred thirty-two patients at 16
      centers were enrolled in this randomized, parallel-group study. The three
      treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82);
      tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and
      tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study
      duration was 6 months, and patients were followed up for patient and graft
      survival for 12 months. RESULTS: At 6 months posttransplantation, daily doses of
      1 g and 2 g of MMF were associated with significantly lower rates of acute
      rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%,
      24.9%, and 22.9%, respectively, for the three treatment groups when acute
      rejection was determined by clinical criteria (P=0.007). At month 12, patient
      survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%,
      92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group,
      respectively. Gastrointestinal adverse events and leukopenia were higher in the
      MMF groups, especially in the MMF-2 g group (P<0.05). CONCLUSIONS: Low-dose
      tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an
      optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated
      with greater toxicity without a significant improvement in efficacy.

PMID- 11468537
TI  - The influence of acute rejection on long-term renal allograft survival: a
      comparison of living and cadaveric donor transplantation.
AB  - BACKGROUND: We investigated whether recipients of living donor grafts who suffer
      an acute rejection progress to graft loss because of chronic rejection at a
      slower rate than recipients of cadaveric grafts. METHODS: A retrospective review
      was made of 296 renal transplantations performed at Mount Sinai Hospital. Only
      grafts functioning for at least 3 months were included in this analysis.
      Demographic variables of donor and recipient age, race, sex, and serum creatinine
      at 3 months after transplantation were compared between groups. RESULTS: Among
      the acute rejection-free cohort, the estimated 5-year graft survival was 90% for
      those receiving transplants from living relatives and 88% for those receiving
      cadaveric transplants (P=0.76). However, in grafts with early acute rejection,
      the 5-year survival was 40% for cadaveric recipients compared with 73% for living
      related graft recipients (P<0.014). Using the proportional hazards model,
      cadaveric donor source, older donor age, African American recipient race, and
      elevated 3-month serum creatinine were independent predictors of long-term graft
      loss caused by chronic rejection. The severity of acute rejection and recipient
      age had no impact on the risk of graft loss because of chronic rejection.
      CONCLUSION: These data indicate that the benefit of living related
      transplantation results from the fact that a living related graft progresses from
      acute to chronic rejection at a slower rate than a cadaveric graft. Furthermore,
      a cadaveric graft that is free of acute rejection 3 months after transplantation
      has an equal likelihood of functioning at 5 years as that of a graft from a
      living related donor.

PMID- 11468538
TI  - Control of antidonor antibody production with tacrolimus and mycophenolate
      mofetil in renal allograft recipients with chronic rejection.
AB  - BACKGROUND: In renal transplantation, chronic rejection is a major cause of late
      allograft loss. Recent studies indicate that a subset of chronic rejection is
      associated with anti-HLA donor specific antibodies (DSA) and complement C4d
      deposition in peritubular capillaries (PTC). Since rescue therapy with tacrolimus
      and mycophenolate mofetil has been found to limit antidonor B-cell responses in
      recipients with acute humoral rejection, we sought to determine whether a similar
      immunosuppressive regimen might be effective in patients with 'chronic humoral
      rejection'. METHODS: Four renal allograft recipients with 'chronic humoral
      rejection' were prospectively identified. The diagnosis was based on: (1)
      progressive rise in serum creatinine over 12 months; (2) typical pathologic
      features by light microscopy (transplant arteriopathy and glomerulopathy); (3)
      widespread C4d deposits in PTC by immunofluorescence; (4) detection of 'de novo'
      DSA at the time of biopsy. Maintenance immunosuppression was CsA, prednisone and
      azathioprine (n=3) or prednisone and azathioprine (n=1). Rescue therapy with
      tacrolimus and mycophenolate mofetil was initiated in all patients, 12 hr after
      cyclosporine and azathioprine discontinuation. RESULTS: At diagnosis, the mean
      serum creatinine was 3.9 mg/dl (range: 3.3 to 5.4 mg/dl). DSA was an IgG directed
      against HLA class II (n=3) or class I (n=2), that is one patient had both anti
      HLA class I and class II antibodies. Pretreatment antibody titers varied between
      1:8 and 1:128. Rescue therapy was associated with a rapid and sustained decrease
      in antibody titers. In two patients, DSA became undetectable after 9 months and a
      repeat biopsy performed after 12 months revealed a decrease in C4d deposition in
      PTC. CONCLUSION: These results suggest that a decrease in DSA production can be
      induced in renal allograft recipients with 'chronic humoral rejection' by using
      an immunosuppressive regimen that combines tacrolimus and mycophenolate mofetil.
      Limitation of antidonor antibody synthesis may be important for the treatment or
      the prevention of chronic rejection in organ transplantation.

PMID- 11468539
TI  - Parameters of high bone-turnover predict bone loss in renal transplant patients:
      a longitudinal study.
AB  - BACKGROUND: Osteoporosis is a serious complication of kidney transplantation.
      Various factors have been postulated to contribute to posttransplant bone loss,
      among them treatment with corticosteroids, the use of cyclosporine and
      cyclosporine-like agents, and persistent hyperparathyroidism. In a previous cross
      sectional study of long-term renal transplant recipients, we observed that
      osteoporosis or osteopenia was present in 88% of patients. Because biochemical
      markers of bone formation (serum osteocalcin) and bone resorption (urine
      pyridinoline, PYD, and deoxypyridinoline, DPD) were elevated in the majority of
      study subjects, we hypothesized that elevated rates of bone-turnover contribute
      to posttransplant bone loss in long-term renal transplant patients. This study
      was performed to examine this hypothesis. METHODS: The study population was
      composed of 62 patients who were more than 1-year postrenal transplantation and
      who had preserved renal function. They were followed prospectively for 1 year.
      Biochemical markers of bone-turnover were measured at study entry, and patients
      were classified as having high bone-turnover based on elevated urinary levels of
      at least one marker of bone resorption (i.e., PYD or DPD) and/or serum
      osteocalcin (group 1). If none of these were present, they were classified as
      having normal bone-turnover (group 2). Bone mineral density (BMD) was measured by
      dual energy x-ray absorptiometry (DEXA) at time of entry into the study and again
      after 1 year of follow-up. The changes in BMD at the lumbar spine, hip, and wrist
      over the period of the study were compared between the high and normal bone
      turnover groups. RESULTS: Forty-three patients (69%) were classified as having
      high bone-turnover (Group 1), and 19 patients (31%) were classified as having
      normal bone-turnover (Group 2). There was a statistically significant difference
      in change in BMD between the two groups at the lumbar spine (-1.11+/-0.42%, high
      bone-turnover, vs. 0.64+/-0.54%, normal bone-turnover; P=0.02) and the hip (
      0.69+/-0.38%, high bone-turnover, vs. 1.36+/-0.66%, normal bone-turnover;
      P=0.006). Whereas group 2 had stable bone mass, group 1 exhibited bone loss at
      these skeletal sites. CONCLUSIONS: Our results indicate that bone loss is greater
      in renal transplant recipients with elevated biochemical markers of bone
      turnover, suggesting that these markers may be useful in identifying patients at
      risk for continued bone loss. These data support the hypothesis that continued
      bone loss in long-term renal transplant recipients is associated with high bone
      turnover. If accelerated bone resorption does play a role in posttransplant bone
      loss, this would provide a strong rationale for use of antiresorptive therapy for
      the prevention and treatment of this complication.

PMID- 11468540
TI  - N-terminal fragments of the proatrial natriuretic peptide in plasma and urine of
      kidney graft recipients.
AB  - BACKGROUND: Successful kidney transplantation normalizes elevated proatrial
      natriuretic peptide (proANP) plasma concentrations of renal failure patients in
      the early posttransplant period. We evaluated plasma and urinary proANP fragments
      in the late posttransplant period. METHODS: Immunoreactive proANP(1-30) and
      proANP(31-67) were determined in 389 renal transplant (Rtx) recipients in the
      long-term, follow-up period and in 16 healthy controls. RESULTS: Rtx recipients
      had significantly higher concentrations of proANP(1-30) and proANP(31-67) in both
      plasma and urine than healthy controls. Although their graft function was normal,
      all of these long-term Rtx recipients were taking glucocorticoids, which increase
      proANP(1-30) and proANP(31-67) in the circulation to the extent found in this
      investigation. Two-thirds of these recipients were also taking cyclosporine,
      which also increases atrial peptides. Urinary proANP(31-67) was significantly
      higher than urinary proANP(1-30); 5.5-fold in Rtx patients and 2-fold in
      controls. Deterioration of renal graft function was associated with a rise of
      plasma proANP(1-30) from 0.98+/-0.66 to 6.28+/-3.55 nmol/l (P<0.0001) and plasma
      proANP(31-67) from 1.81+/-1.04 to 7.89+/-3.76 nmol/l (P<0.0001). Urinary
      excretion of proANP(1-30) increased from 0.27+/-0.34 to 5.96+/-5.07 nmol/24 hr
      (P<0.0001) and proANP(31-67) from 1.45+/-0.85 to 12.23+/-5.12 nmol/24 hr
      (P<0.0001). Also proteinuria enhanced plasma and urinary proANP fragments.
      CONCLUSIONS: ProANP(1-30) and proANP(31-67) of Rtx recipients are affected by
      immunosuppression, hypertension, renal failure, and proteinuria. One would have
      expected proANP(1-30) and proANP(31-67) not to normalize because of the
      glucocorticoids that they were receiving.

PMID- 11468541
TI  - Long-term results of living-related donor liver graft transplantation: a single
      center analysis of 110 transplants.
AB  - BACKGROUND: Difficulties of cadaveric donation and serious donor shortage have
      led to the development and popularization of living-related donor liver graft
      transplantation (LRLT). Because the history of this procedure is rather short,
      important aspects specific to this procedure have not been sufficiently
      documented. The objective of this study was to analyze a single center's 10-year
      experience with 110 LRLT in pediatric and adult patients with end-stage liver
      diseases. METHODS: The medical records of 110 consecutive patients who underwent
      LRLT were reviewed. The recipients were comprised of 72 children and 38 adults.
      The graft volume corresponded to 26-192% of the recipient's standard liver
      volume. The relationship between pretransplant covariates and patient and graft
      survival was analyzed. Actuarial patient/graft survival rates were determined at
      1, 3, and 5 years. The type and incidence of posttransplant complications were
      analyzed, as was long-term graft function. RESULTS: The 1-, 3-, and 5-year
      actuarial patient and graft survival rates were 88%, 85%, and 85%, respectively.
      Log-rank test demonstrated that ABO-compatibility predicted patient survival
      rate, whereas patient age, underlying disease, patient's clinical status, donor
      recipient relation, donor age, and graft volume/standard liver volume ratio did
      not. Long-term liver function remains excellent. All the donors have returned to
      normal daily lives with an uneventful course. CONCLUSIONS: LRLT is an efficacious
      procedure that provides excellent short-term and long-term survival. The
      indication criteria for both recipient and donor were legitimate in this series,
      except for transplant across ABO-incompatibility. Cautious expansion of this
      procedure may be justified under the situation of serious shortage of cadaveric
      donor.

PMID- 11468542
TI  - Returning to school after heart or heart-lung transplantation: how well do
      children adjust?
AB  - BACKGROUND: Up to 40% of children and adolescents with chronic illness experience
      school-related problems, including learning difficulties and problems in social
      adjustment and peer relationships. Despite the life-threatening nature of heart
      and heart-lung transplantation and the severity of illness, which results in the
      necessity for surgery, there is little information on the school performance of
      children after transplantation. METHODS: Eighty-one children and adolescents were
      assessed with regard to their academic attainments and behavior at school at
      regular intervals after heart (n=47) or heart-lung (n=34) transplantation and
      comparisons made with a group of healthy children. RESULTS: Cognitive ability and
      performance on academic attainments were within the normal range and did not
      change significantly as a function of time since transplant. However, performance
      was at a significantly lower level than that of the healthy children. Although
      the prevalence of behavior problems was only 8% at 6 months posttransplant, at 3
      years, it had increased to 29% and, at 5 years, it was still 27%. Children with
      an initial diagnosis of congenital heart disease had more academic and behavioral
      difficulties than those with either cardiomyopathy or cystic fibrosis.
      CONCLUSIONS: A significant number of children who had undergone successful
      transplantation experienced difficulties at school. Contrary to expectations,
      educational problems were more prevalent in the medium term, rather than short
      term, after transplant. Initial diagnosis was a salient factor in posttransplant
      psychological functioning at school. Early intervention and close liaison with
      schools is indicated to reduce psychological morbidity and enhance adaptation
      within the school environment.

PMID- 11468543
TI  - Reduction of left ventricular mass by lisinopril and nifedipine in hypertensive
      renal transplant recipients: a prospective randomized double-blind study.
AB  - BACKGROUND: Cardiovascular disease is the dominant cause of death in renal
      transplant recipients. Left ventricular hypertrophy (LVH) is a known risk factor.
      After renal transplantation, persistent hypertension is an important determinant
      for the further evolution of LVH. The aim of the present study was to compare the
      effect of an angiotensin converting enzyme (ACE) inhibitor (lisinopril) with a
      calcium channel blocker (CCB) (controlled release nifedipine) in treatment of
      posttransplant hypertension focusing on changes in LVH. METHODS: One hundred
      fifty-four renal transplant recipients presenting with hypertension (diastolic
      BP> or =95 mmHg) during the first 3 weeks after transplantation were randomized
      to receive double-blind 30 mg nifedipine or 10 mg lisinopril once daily. RESULTS:
      One hundred twenty-three patients completed 1 year of treatment. Good quality
      echocardiographic data were available in 116 recipients (62 nifedipine/54
      lisinopril) 2 and 12 months posttransplant. Blood pressure was equally well
      controlled in the two groups throughout the study (mean systolic/diastolic+/-SD
      after 1 year: 140+/-16/87+/-8 mmHg with nifedipine and 136+/-17/85+/-8 mmHg with
      lisinopril). Left ventricular mass index was reduced by 15% (P<0.001) in both
      groups (from 153+/-43 to 131+/-38 g/m2 with nifedipine and from 142+/-35 to 121+/
      34 g/m2 with lisinopril). There were no statistically significant differences
      between the two treatment groups at baseline or at follow-up. CONCLUSIONS: In
      hypertensive renal transplant recipients with well-controlled blood pressure,
      there is a regression of left ventricular mass after renal transplantation. The
      regression of left ventricular mass index is observed to a similar extent in
      patients treated with lisinopril or nifedipine.

PMID- 11468544
TI  - A prospective trial of inhaled nitric oxide in clinical lung transplantation.
AB  - BACKGROUND: Reperfusion injury (RI) is a major cause of mortality and morbidity
      among lung transplant recipients. We sought to determine if prophylactic
      administration of inhaled nitric oxide (NO) to lung transplant recipients at
      reperfusion would prevent RI. We also hypothesized that if prophylactic NO proves
      ineffective in preventing RI then it may improve pulmonary hemodynamics and gas
      exchange in the subset of patients who develop RI. METHODS: After informed
      consent, 28 consecutive, adult lung transplant recipients received NO at 20 ppm
      at reperfusion. NO was withdrawn for 15 min at 6 and 12 hr after reperfusion, and
      gas exchange and hemodynamics were measured. RESULTS: Five of the 28 lung
      transplant recipients (18%) developed RI. Withdrawal of NO for 15 min in this
      subset of patients resulted in a significant rise in mean pulmonary artery
      pressure and a reduction in oxygenation index. All five patients with RI were
      kept on inhaled NO until full functional recovery of the allograft and were then
      weaned from mechanical ventilation. None required extracorporeal membrane
      oxygenation support; the early mortality in this group was 20% (1/5). The
      remaining 23 patients without RI had uneventful early postoperative course and
      were weaned from NO and mechanical ventilation within 36 hr of transplantation.
      CONCLUSIONS: Prophylactic-inhaled NO does not prevent RI in human lung
      transplantation. However, inhaled NO, started at reperfusion, improves gas
      exchange and reduces pulmonary artery pressure in those patients who develop RI.

PMID- 11468545
TI  - Alloreactivity of natural killer cells in allogeneic liver transplantation.
AB  - BACKGROUND: The cytolytic attack of natural killer (NK) cells is blocked by
      recognition of the idiotypic phenotype of certain polymorphisms in HLA class I
      molecules, specifically by HLA-C alleles (Asn77, Lys80 or Ser77, Asn80) or HLA
      Bw4 allotypes. Because liver allograft rejection is associated closer with
      mismatch in HLA class I than class II, we investigated the role of NK cells in
      acute hepatic allograft rejection in vivo/in vitro. METHODS: The HLA pattern was
      typed with serological and polymerase chain reaction (PCR) techniques. In 31
      liver transplantations, mononuclear cells from donor spleen and peripheral blood
      of recipients (before/after transplantation) were cultured in mixed lymphocyte
      cultures (MLC). MLC-derived effector cells were analyzed by flow cytometry and
      tested in 51Cr-release assays. RESULTS: Patients with NK allospecific
      constellations tended to have higher numbers of NK cells in peripheral blood
      during the first 4 weeks after transplantation, and patients' lymphocytes
      stimulated with donor cells had a significantly higher cytotoxic activity on days
      14 and 21 compared with patients without NK allospecificity. However, acute
      rejection occurred with similar frequency in both groups (31% with allospecific
      constellations vs. 40% without). Moreover, acute rejection episodes were not
      associated with an increase in NK cells in vivo or enhanced cytotoxicity of NK
      cells to donor target cells. CONCLUSIONS: Under standard immunosuppressive
      therapy, NK allospecific constellations did not seem play a major role in acute
      hepatic allograft rejection. Strategies to prevent or treat NK allospecific
      constellations after liver transplantation are not likely to reduce the incidence
      or severity of acute allograft rejection.

PMID- 11468546
TI  - Skin-specific alloantigens in miniature swine.
AB  - BACKGROUND: The acceptance of skin allografts has historically been among the
      most challenging problems in the field of transplantation, attributed, at least
      in part, to the existence of antigens expressed by skin but not by other tissues.
      Many studies have suggested the existence of skin-specific antigens in rodents,
      but data in large-animal models are more limited. METHODS: We have recently
      developed protocols for attaining stable mixed hematopoietic chimerism in
      miniature swine, using MHC-matched donors and recipients. We have now assessed
      tolerance to donor-derived skin and cardiac allografts in these chimeric animals.
      RESULTS: Skin-graft rejection was seen in four of six animals receiving skin
      grafts taken from the respective hematopoietic donors. In the other two animals,
      donor-derived skin grafts survived indefinitely. No cardiac-allograft rejection
      was observed in mixed-chimeric animals that received heart transplants from their
      hematopoietic donors, even in animals that had already rejected skin allografts
      from the same donors. In all animals assessed, in vitro hyporesponsiveness to
      donor hematopoietic cells persisted. CONCLUSION: These findings support the
      concept that skin expresses immunogenic alloantigens that either are not
      expressed or are not immunogenic in cardiac or hematopoietic tissue.

PMID- 11468547
TI  - Human CD154 induces activation of porcine endothelial cells and up-regulation of
      MHC class II expression.
AB  - BACKGROUND: CD40 is expressed on a number of antigen-presenting cells and also on
      vascular endothelium. It has been shown that engagement of CD40 on vascular
      endothelium by CD154 on platelets and CD154-bearing cell lines leads to the
      induction of adhesion molecule expression. Having cloned porcine CD40, and shown
      that it is capable of binding human CD154, we investigate whether human CD154 can
      activate porcine endothelial cells (EC) through CD40 ligation. METHODS: Human
      Jurkat clone D1.1 (CD154+), or clone E6.1 (CD154-), were co-cultured with EC from
      pig aorta and human aorta and umbilical vein for various times in the presence or
      absence of blocking antibody to CD154. RESULTS: Human and pig EC were shown to
      express CD40 by flow cytometry by using soluble human CD154 (CD154Ckappa). Co
      culture of pig EC with CD154-expressing Jurkat D1.1 cells led to the induction of
      E-selectin by 6 hr (peak 24 hr) and vascular cell adhesion molecule-1 (VCAM-1) by
      6 hr (peak 48 hr). Similar results were also observed with human EC. Porcine EC
      were induced to up-regulate major histocompatibility complex class II at 24 hr by
      co-culture with Jurkat D1.1 cells through a CD40-dependent mechanism. In
      contrast, no up-regulation was observed on human EC. CONCLUSIONS: A number of
      cells can express CD154, including T cells, natural killer cells, and platelets,
      and these could signal graft EC through the CD40 pathway. These results
      demonstrate a possible role for the CD40 pathway in the activation of vascular
      endothelium in the rejection of porcine xenografts.

PMID- 11468548
TI  - Patterns of engraftment in different strains of immunodeficient mice
      reconstituted with human peripheral blood lymphocytes.
AB  - BACKGROUND: Models of immunodeficient mice reconstituted with a competent human
      immune system would represent an invaluable tool for the study of transplantation
      immunobiology allergy, autoimmunity, and infectious diseases. Severe combined
      immune deficiency (scid) mice can be successfully reconstituted with human
      peripheral blood lymphocytes (PBLs), but rates and levels of engraftment are
      poor. New strains of mice with diverse immunodeficiencies have been recently
      characterized or developed, which might prove to be advantageous for in vivo
      studies of human immune reactivity. METHODS: We have compared rates and patterns
      of human PBL engraftment in four available immunodeficient murine strains; scid
      beige, nonobese diabetic (NOD)-scid, NOD-scid-beta2 m- and rag-. T- and B
      lymphocyte engraftment, phenotype of engrafted cells, and occurrence of graft
      versus-host disease (GVHD) were studied and compared. RESULTS: Successful
      engraftment of human PBL was readily obtained in the majority of scid-beige, NOD
      scid, and NOD-scid-beta2 m- with a single i.p. administration of human PBLs,
      whereas it was seldom achieved in rag- animals. Human Ig levels were accordingly
      remarkably low in rag- recipients but, interestingly also in NOD-scid-beta2 m-
      mice. Engraftment was readily observed not only in peripheral blood but also in
      spleen and bone marrow of successfully reconstituted animals. Phenotypic analysis
      of engrafted human cells showed preserved CD4/CD8 ratios and a clear skewing
      toward an activated phenotype. GVHD was invariably observed in successfully
      reconstituted animals. CONCLUSIONS: Our data indicate that a high rate of
      reconstitution with human lymphocytes can be achieved in scid-beige, NOD-scid,
      and NOD-scid-beta2 m- mice. Human Ig are produced at high levels, except in NOD
      scid-beta2 m-, including xenoreactive natural antibodies. Scid-beige and NOD-scid
      appear therefore better suited than NOD-scid-beta2 m- or rag- for analysis of
      human immunoreactivity in vivo. An important caveat is the invariable occurrence
      of GVHD that precludes long-term studies in this model system.

PMID- 11468549
TI  - Increased human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes
      after lung transplantation correlates with HCMV pneumonitis.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) reactivation and disease remain
      relatively common in lung transplant recipients (LTR) despite the use of
      ganciclovir prophylaxis protocols for all HCMV at-risk patients. The specific
      aims of this study were to (1) describe the HCMV DNA viral load in the peripheral
      blood leukocytes (PBL) of a cohort of LTR during the first 6 months after lung
      transplantation; (2) prospectively determine whether HCMV DNA viral load predicts
      episodes of HCMV pneumonitis in LTR; and (3) study the effect of ganciclovir on
      HCMV viral load. METHODS: Competitive polymerase chain reaction using an internal
      standard and fluorometric detection were used to quantitate HCMV DNA in the PBL
      of a cohort of 26 LTR monthly for the first 6 months after transplantation (145
      samples). All patients were treated with standard triple immunosuppression, and
      ganciclovir prophylaxis was given to all at-risk LTR (donor or recipient HCMV
      seropositive) for at least 8 weeks after transplantation. RESULTS: Thirteen
      episodes of histopathologically proven HCMV pneumonitis in nine subjects occurred
      during follow-up with a wide intra- and intersubject variation in the HCMV DNA
      PBL levels. HCMV detection had a sensitivity of 92% and specificity of 76% for
      HCMV pneumonitis (negative likelihood ratio, 9.5), whereas greater than 10-fold
      increases in HCMV DNA load had a specificity of 93% and sensitivity of 67%
      (positive likelihood ratio, 11). HCMV DNA detection had an adjusted odds ratio
      for HCMV pneumonitis of 107 (95% confidence interval, 14-821; P<0.005). In those
      with detectable HCMV DNA in PBL (n=44), HCMV DNA levels were 4.4 (95% confidence
      interval, 1.2-16.8) times higher in those with HCMV pneumonitis than in those
      without HCMV pneumonitis. Although ganciclovir treatment was very effective in
      treating HCMV pneumonitis and suppressing HCMV DNA levels, thrice weekly
      ganciclovir prophylaxis only partially controlled HCMV DNA levels and did not
      eliminate HCMV pneumonitis risk as three patients developed HCMV pneumonitis
      while on this regimen. CONCLUSIONS: HCMV DNA detection, absolute levels, and
      relative change from baseline in the PBL of LTR correlate with HCMV pneumonitis
      episodes and may be a useful intermediate outcome measure of the efficacy of
      ganciclovir prophylaxis and treatment strategies.

PMID- 11468550
TI  - Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal
      alpha(1,3)gal target antigens in the gal knockout mouse.
AB  - BACKGROUND: Natural antibodies that react with galactose-alpha(1,3)galactose
      [galalpha(1,3)gal] carbohydrate epitopes exist in humans and Old World primates
      because of the inactivation of the alpha1,3-galactosyltransferase (alpha1,3GT)
      gene in these species and the subsequent production of antibodies to
      environmental microbes that express the galalpha(1,3)gal antigen. The Gal
      knockout (Gal o/o) mouse, produced by homologous disruption of the alpha1,3GT
      gene, spontaneously makes anti-galalpha(1,3)gal antibodies and can be used to
      study the genetic control of humoral immune responses to this carbohydrate
      epitope. METHODS: Six hybridomas that produce monoclonal antibodies (mAbs) to
      galalpha(1,3)gal were generated in Gal o/o mice. The mAbs were tested to
      characterize the binding activity with flow cytometry using pig aortic
      endothelial cells and ELISA with galalpha(1,3)gal carbohydrates. The VH and VK
      genes of these hybridomas were cloned, sequenced, and analyzed. RESULTS: The mAbs
      showed distinct patterns of antibody binding to galalpha(1,3)gal antigens. The VH
      genes that encode the mAb binding activity were restricted to a small number of
      genes expressed in their germline configuration. Four of six clones used closely
      related progeny of the same VH germline gene (VH441). Comparison of the mouse
      gene VH441 to the human gene IGHV3-11, a gene that encodes antibody activity to
      galalpha(1,3)gal in humans, demonstrates that these two genes share a nonrandom
      distribution of amino acids used at canonical binding sites within the variable
      regions (complimentary determining regions 1 and 2) of their immunoglobulin VH
      genes. CONCLUSIONS: These results demonstrate the similarity of the Gal o/o mice
      and humans in their immune response to galalpha(1,3)gal epitopes. Gal o/o mouse
      can serve as a useful model for examining the genetic control of antibody/antigen
      interactions associated with the humoral response to pig xenografts in humans.

PMID- 11468551
TI  - Roux-en-Y gastric bypass for recurrent nonalcoholic steatohepatitis in liver
      transplant recipients with morbid obesity.
AB  - BACKGROUND: Severe obesity is common before and after liver transplantation and
      has been associated with significant morbidity and mortality. Furthermore, it may
      cause graft dysfunction through the development of recurrent nonalcoholic
      steatohepatitis. METHODS: We performed Roux-en-Y gastric bypass in two morbidly
      obese patients who had undergone liver transplantation and had graft dysfunction
      secondary to recurrent nonalcoholic steatohepatitis. RESULTS: Both patients
      demonstrated dramatic weight loss and had normalization of liver enzymes, lipids,
      and glucose levels. Repeated liver biopsy showed regression of steatosis.
      CONCLUSIONS: Roux-en-Y gastric bypass can be successfully performed in liver
      transplant recipients with morbid obesity and may lead to weight loss, correction
      of metabolic abnormalities, and regression of hepatic dysfunction secondary to
      recurrent steatosis.

PMID- 11468552
TI  - Transjugular intrahepatic portosystemic shunt approach and local thrombolysis for
      treatment of early posttransplant portal vein thrombosis.
AB  - Early portal vein thrombosis is a rare but severe posttransplant complication
      that may lead to graft and/or patient loss. Transjugular intrahepatic
      portosystemic shunting and local thrombolysis may represent an easy solution to
      this major complication of liver transplantation.

PMID- 11468553
TI  - Sirolimus-associated eyelid edema in kidney transplant recipients.
AB  - BACKGROUND: The immunosuppressant sirolimus is effective in preventing acute
      rejection episodes. So far, unusual edema formation has not been reported as a
      side effect. METHODS: Two groups of patients with renal transplants, consisting
      of 11 patients each, were followed for up to 29 months. The immunosuppressive
      regimen was either sirolimus and prednisone with or without cyclosporine or
      azathioprine/mycophenolate and prednisone with cyclosporine. Routine follow-up
      included a thorough clinical investigation. Edema formation was documented
      photographically. RESULTS: In 5 of the 11 patients treated with sirolimus uni- or
      bilateral, non-itching, eyelid edema was observed. After discontinuation of
      sirolimus, lid edema disappeared. The duration until recovery varied from weeks
      to months. No cause of edema formation other than the treatment with sirolimus
      was detected. CONCLUSIONS: Severe eyelid edema formation seems to be associated
      with sirolimus treatment. The underlying mechanism is unknown.

PMID- 11468554
TI  - Expression of vascular endothelial growth factor and its receptors Flt-1 and
      KDR/Flk-1 in chronic cyclosporine nephrotoxicity.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell
      mitogen involved in angiogenesis, wound healing, and inflammation. METHODS: Rats
      placed on low salt diet (LSD) or normal salt diet (NSD) were treated with
      cyclosporine (CsA) or vehicle (VH) and killed at 7 or 28 days. We studied the
      expression of VEGF and its receptors Flt-1 and KDR/Flk-1 mRNA by Northern and
      that of VEGF protein by Western blot. RESULTS: CsA induced VEGF mRNA and protein
      expressions at 7 and 28 days in LSD rats. At 7 days, CsA up-regulated the
      expression of Flt-1 and KDR/Flk-1 receptors; however, at 28 days, Flt-1 remained
      unchanged whereas KDR/Flk-1 expression declined. In NSD rats, in which the lesion
      did not develop, the expression of VEGF and its receptors remained similar to
      control. CONCLUSIONS: What causes VEGF to be up-regulated remains unclear.
      Further studies are needed to study the role of hypoxia and other cytokines in
      relation to VEGF in this model.

PMID- 11468555
TI  - Combined FTY720/cyclosporine treatment promotes graft survival and lowers the
      peripheral lymphocyte count in a murine cardiac allotransplantation model.
AB  - BACKGROUND: FTY720 lowers the peripheral lymphocyte count (PLC) by accelerating
      the migration of circulating lymphocytes to secondary lymphoid organs. We
      investigated the efficacy of combined FTY720+cyclosporine (CsA) treatment versus
      monotherapy on prolonging graft survival and on lowering the PLC. METHODS: BALB/c
      hearts were heterotopically grafted in C3H mice. FTY720 was administered alone or
      in combination with CsA. PLC and body weight were determined on day 7, day 28, or
      the day of rejection. RESULTS: Combining FTY720 with CsA prolonged, dose
      dependently and significantly, the allograft survival. FTY720, but not CsA,
      lowered the PLC dose-dependently. The granulocyte count was not reduced in any
      group. FTY720 concentrations were not influenced by the CsA co-administration.
      CONCLUSIONS: Combined FTY720 and CsA treatment was well tolerated, promoted graft
      survival, and suppressed the inflammatory allo-response. The PLC lowering
      correlated well with the antirejection effects in the two-drug regimens,
      suggesting that the PLC might guide FTY720 therapy at low doses.

PMID- 11468556
TI  - Laminin-mediated interactions in heart graft rejection.

PMID- 11468558
TI  - [Pathology in the new era of healthcare economics].

PMID- 11468559
TI  - [Activity and cost analysis in surgical pathology. Experience of a French
      university laboratory using the activity-based costing method].
AB  - Good self-knowledge enables us to have a well- reasoned adaptation to our
      environment. Starting from this precept based on simple common sense, activity
      and cost analysis, when applied to medical departments in a university hospital
      setting, represents a necessary phase in their scientific progression and in the
      continuation of their university vocation. This is all the more true given the
      present climate of economic and organizational restructuring of medical
      facilities. This paper relates the experience of a French surgical pathology
      department which was assessed for cost effectiveness using the Activity-Based
      Costing (ABC) method in 1999. This method, which originated in the business world
      and of which the general concepts are presented here, has given us a keener
      understanding of the diverse processes involved, their costs and how these costs
      are arrived at. Moreover, this method has identified the proportion of costs
      imputable to diagnostic work and of those linked to work specific to a university
      hospital, in particular teaching and research and development. The results can
      then be used for a clearer analysis of the figures required by prescribers and
      health care funding agencies, and, within the department, to enhance perception
      of work carried out by the entire staff in order to initiate a new type of
      management centered on activity (Activity-Based Management). Adaptable to any
      medical department, whatever its organizational structure, independent of the
      significance of any given code letter and regardless of the rating method used to
      grade activities, the ABC method also allows for comparisons between structures
      of a similar nature. The thoughts it inspires on economic performance must take
      into account the rules of good medical practice, the imperatives of quality
      assurance, the need for "breathing space" which are indispensable to research and
      a humanist conception of working relations.

PMID- 11468560
TI  - [Position of cervix cancer detection in Gabon over a period of 19 years].
AB  - MATERIALS AND METHODS: We report the contribution of the cytology test for
      screening for cervix cancer in Gabon observed in a retrospective study over 19
      years (1977-1995). Data from the Libreville Faculty of Medicine
      cytohistopathology laboratory were used. RESULTS: Over the 19-year period, 10,838
      PAP smears were performed, an average of 570,42 smears per year. Sixty-eight
      cases of cervix cancer were diagnosed with this test: 40 invasive carcinomas
      (58.83%), 5 microinvasive carcinomas (7.35%), and 23 in situ carcinomas (33.82%).
      During the same period, 437 cervix cancers were reported in the same laboratory
      without prior cytology test. CONCLUSION: In Gabon, cervix cancer is usually
      diagnosed at an invasive stage, hence the need for systematic detection.

PMID- 11468561
TI  - Pituitary adenomas.
AB  - Human pituitary adenomas are benign neoplasms composed of hormonal
      adenohypophyseal cells. They arise in the sella turcica, and are characterized by
      a wide range of biological behavioral related not only to hormonal but also to
      proliferative activities. In the past, pituitary adenoma studies have mainly been
      devoted to histological and ultrastructural classification improved by
      immunohistochemical techniques. Molecular biology, cytogenetic studies,
      associated to experimental animal models, transgenic and knockout mice
      technologies, have allowed new approaches, especially concerning pathogenesis and
      progression. It became obvious that tumorigenesis has to be considered as a
      multistep event, inasmuch as different factors share numerous homologies. On the
      other hand, it could be supposed that the knowledge of the biological
      aggressiveness could led to an appropriate follow-up as well as specific therapy.

PMID- 11468562
TI  - [Prostatic intraepithelial neoplasia].
AB  - Prostatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly
      associated with prostate cancer and has been postulated to be a pre-malignant
      lesion. However, much of the natural history of PIN remains unknown. A more
      fundamental understanding of the relationship between PIN and invasive tumors at
      the molecular level is critically needed and represents an important future
      challenge for investigators. The importance of their recognition are based on the
      correlation between their presence and the existence of prostatic
      adenocarcinomas. It seemed significant to us to point out the criteria of the
      diagnosis and the action to be taken in front of the discovery of such lesions on
      biopsies in prostate sufferers.

PMID- 11468563
TI  - [Angiomatoid fibrous histiocytoma: a rare pathologic entity].
AB  - Angiomatoid fibrous histiocytoma is an unusual tumor, affecting primarily young
      adults who develop local disease with favorable prognosis. This contrasts with
      the aggressive natural history of malignant fibrohistiocytoma. We report case of
      a 9-year-old girl who presented with a tumor mass of soft tissues with an unusual
      deep location, thereby with non distinctive clinical features. Surgical treatment
      was performed.

PMID- 11468564
TI  - [Atypical teratoid and rhabdoid tumor. Report of a congenital case].
AB  - The atypical teratoid rhabdoid tumor is a rare brain tumor of childhood. We
      report a congenital case, revealed by peripheral facial palsy. This polymorphous
      tumor consisted of rhabdoid cells associated with areas of primitive
      neuroectodermal tumor. The immunoreactivity for the three proteins vimentin,
      epithelial membrane antigen and smooth-muscle actin was suggestive of rhabdoid
      tumor. Genetic study showed a homozygous mutation in the tumoral DNA and a
      constitutional heterozygous mutation, as it was demonstrated in atypical teratoid
      rhabdoid tumors and in renal and extra-renal rhabdoid tumors.

PMID- 11468565
TI  - [Primary uterine and vulvar Ewing's sarcoma/peripheral neuroectodermal tumors in
      children: two unusual locations].
AB  - Two genital cases of Ewing's sarcoma/peripheral neuroectodermal tumor in 14 and
      15 year old teenagers are reported. They arose in uteri and vulva, as small round
      cell tumors with some rosette-like formations and intense membranous
      immunoreactivity for CD99. The EWS/FLI-1 transcript was present in the vulvar
      tumor. Under chemotherapy, uterine tumor outcome was fatal within 9 months. The
      vulvar lesion was treated by surgery and chemotherapy, without relapse after 7
      months. Likewise to these 2 cases, the literature seems to indicate different
      prognosis for uterine and vulvar tumors.

PMID- 11468566
TI  - [An uncommon tumor of the breast].

PMID- 11468567
TI  - [A steady cutaneous nodule].

PMID- 11468568
TI  - [Unusual pulmonary nodules].

PMID- 11468569
TI  - [Particular gastric involvement].

PMID- 11468570
TI  - [Unexpected endobronchial tumor].

PMID- 11468571
TI  - [A macroglobulinemia with an unusual bone marrow aspect].

PMID- 11468572
TI  - [Idiopathic inflammatory myopathies].

PMID- 11468573
TI  - [Mucosal endoscopic resections].
AB  - Endoscopic mucosectomy is a newly developed endoscopic technique allowing the
      resection of large fragments of digestive mucosa. The main indications of this
      technique are the staging and/or the treatment of superficial lesions of
      esophagus, stomach and colon. Resections by endoscopic mucosectomy raise specific
      problems of macroscopic technique and histological analysis. For correct
      inclusion, fragments must be pinned under a rigid support by the endoscopist.
      Their lateral margins must be sampled independently. The fragment must be
      included in totality. The histological report must indicate the depth of the
      resection and its quality, particularly the status of lateral and deep margins.
      The main difficulties of the histological analysis are due to the frequent
      occurrence of coagulation artefacts, which may hamper a correct interpretation of
      the lesions, particularly along the lateral margins. The appropriate management
      of endoscopic mucosal resections requires a good collaboration between
      endoscopists and pathologists.

PMID- 11468574
TI  - [Perisudoral lipoma: a case report to confirm this new entity].

PMID- 11468575
TI  - [Modulation of in vivo fate of drugs: fundamental biopharmaceutical and
      pharmacokinetic aspects].
AB  - The in vivo fate of drugs is basically regulated by the drug's physico-chemical
      properties, and thus depends on its chemical structure. Three successive phases
      describe the fate of exogenous compounds (absorption, distribution, elimination).
      The first two phases can be modulated by galenic formulation. Controlling the
      available dose and release rate by administration route and formulation, allows
      to modulate bioavailability of the active substance and its delivery to the
      general circulation. For distribution, vectorization techniques aim at improving
      the benefit/risk ratio. Two approaches are used: targeting the site of action (or
      avoiding site(s) leading to undesirable effects) and/or specific release rates.

PMID- 11468576
TI  - [Controlled-release drugs: administration routes and formulations].
AB  - The notion of controlled release has been known since the 1930s, but was not
      significantly developed until the 1970s. At that time, Alza introduced the
      concept of a "therapeutic system" and proposed new pharmaceutic formulations.
      Over time, the idea became one of controlled drug delivery and today concerns not
      only one rate of release but also the site of release of the active substance. We
      present here definitions, fundamentals and advantages and disadvantages of
      currently marketed systems and provide examples illustrating oral, transdermal
      and respiratory delivery systems. Current research is also examined.

PMID- 11468577
TI  - [Drug vectorization or how to modulate tissular and cellular distribution of
      biologically active compounds].
AB  - Drug vectorization has undergone considerable development over the last few
      years. This review focuses on the intravenous route of administration. Colloid
      formulations allow a modulation of drug tissue distribution. Using liposomes and
      nanoparticles with unmodified surfaces, drugs can be targeted to macrophages of
      the reticulum endothelium system. When the liposomes or nanoparticles are covered
      with hydrophilic or flexible polymers, the vascular phase can be favored in
      order, for example, to facilitate selective extravasation at a tumor site.
      Therapeutic applications of these systems are presented. The development of
      "intelligent" vectors capable of modulating intracellular distribution of an
      active compounds is an equally interesting approach, for example pH-sensitive
      liposomes or nanoparticles decorated with folic acid capable of targeting
      intracellular cytoplasm.

PMID- 11468578
TI  - [Drug and gene delivery using electrotransfer].
AB  - The use of a low intensity current (iontophoresis) and high voltage pulses
      (electroporation which permeabilizes lipid bilayers) has a potential for the
      administration of conventional and biotechnology-produced drugs. Iontophoresis
      and electroporation enhance transdermal delivery of drugs, including peptides and
      oligonucleotides. Electrochemotherapy, i.e., combination of a systemic or local
      delivery of a non-permeant cytostatic drug with electroporation, kills locally
      tumor cells. Recently, it has been shown that the local injection of a plasmid
      before electroporation increases significantly gene transfection. Hence,
      electrotransfer is a promising alternative for drug and gene delivery.

PMID- 11468579
TI  - [The worldwide challenges of "new" or reemerging communicable diseases at the
      dawn of the 21st century].
AB  - In the first part of this review, AIDS, prion diseases, Hantavirus and arbovirus
      infections, Ebola hemorrhagic fever, legionellosis, hepatitis C, enterotoxigenic
      Escherichia coli infections, Lyme disease, tuberculosis have provided alarming
      examples of emerging or reemerging infectious diseases. In this second part, the
      stress is placed on the reemergence of diphtheria and of serious streptococcal
      infections, on bartonelloses, Chlamydia infections, fungal infections, while
      malaria and cholera are still prevalent in several areas. The increasing
      resistance of too many pathogens to antimicrobial agents is a major source of
      concern, directly related to the challenge of nosocomial infections. An
      infectious cause has been demonstrated (or strongly suspected) for various
      diseases and the scope of infectiology keeps widening, while the threat of
      bioterrorism cannot be neglected. The causes of the emergence or reemergence of
      infectious diseases are multiple and diverse, often in direct relation with human
      activities (population migrations, changes in husbandry or farming practices,
      worldwide exchanges of goods and foods, inadequate uses of antibiotics) but also
      with climatic variations in several areas. The challenge represented by this
      unexpected comeback of infections to the forefront of human and animal pathology
      can only be met with a significant improvement of hygienic practices, cessation
      of certain dangerous behaviors and also, of course, with the development of novel
      antimicrobial molecules (acting on original targets) as well as of a whole series
      of new specific vaccines.

PMID- 11468580
TI  - [Blood ethanol: analytical and forensic aspects].
AB  - An appraisal of the French legislation concerning blood alcohol level is
      presented with a review of all the problems resulting from the interpretation of
      results as well as the relationship to judicial authorities for expert biologists
      and hospital laboratories. Recent results concerning the gaseous exchange of
      ethanol at the pulmonary level give a response to the long lasting contradictory
      debate concerning the ratio, blood alcohol levels - ethylometry. The results of
      recent studies on the digestive metabolism of ethanol explain, at least partly,
      the great variability.

PMID- 11468581
TI  - [Respiratory work and weaning from artificial ventilation. From physiology to
      clinical applications].

PMID- 11468582
TI  - [Adolescence: a violent passage].

PMID- 11468583
TI  - [The working group on endoscopy of the SPLF: new perspectives].

PMID- 11468584
TI  - [Should Ulysses have worn compression stockings? Traveler's thrombosis].

PMID- 11468585
TI  - [Consensus between lung and infectious disease specialists on management of lower
      respiratory tract infections. Comments. Reservations. Perspectives].

PMID- 11468586
TI  - [Chronic infiltative lung disease and viruses].
AB  - A role for viruses in the development or course of the main idiopathic chronic
      infiltrative lung disease has been suggested for a long time. Viruses that have
      usually been incriminated in cryptogenic fibrosing alveolitis are hepatitis C
      virus, whose role has not been accurately proven, and latent viruses including
      Epstein-Barr virus and adenovirus. These latent viruses might be re-activated in
      the lung of patients immunocompromised by treatments and might be accountable for
      disease progression. However, published studies have been very conflicting and
      the only clinical trial testing ribavirin has failed to demonstrate a beneficial
      effect. In sarcoidosis, the responsibility of human herpesvirus 6 and 8 and
      retroviruses has not been proven. Finally, data in the literature do not support
      a link between Langerhans cell histiocytosis and human herpesvirus 6 and 8. These
      viruses may act by several mechanisms: viral proteins may be antigens driving an
      appropriate immune response; they may also behave as transactivating factors to
      control the expression of various genes involved in immune response, cell growth
      or synthesis of matrix proteins.

PMID- 11468587
TI  - [Bronchopulmonary aspergillosis: new developments].
AB  - Bronchopulmonary aspergillosis are in the news. Invasive pulmonary aspergillosis
      raise early diagnostic problems and prevention problems in immunocompromised
      patients. These infections are no unusual in chronic obstructive pulmonary
      disease. The diagnosis between aspergilloma and chronic necrotizing pulmonary
      aspergillosis can be difficult. In allergic bronchopulmonary aspergillosis,
      epidemiology and therapy are questionable. Real progress has been made due to
      thoracic computed tomographic scan and mycological methods. Better use of
      amphotericin B, of amphotericin B lipid formulations and of azole antifungal
      agents, combined with surgical resection if necessary should improve
      aspergillosis prognosis.

PMID- 11468588
TI  - [Home ventilation after intensive care].
AB  - In the course of chronic respiratory insufficiency, acute episodes often require
      the use of mechanical ventilation. Failure of weaning, or worsening of alveolar
      hypoventilation, results in long term ventilatory assistance with the need of
      overall care of the patient. The pneumologist has a key role in the choice of
      indications, devices and mode of home mechanical ventilation. Thanks to the non
      invasive ventilation with a facial or nasal mask, tracheostomy is less often
      needed. Respiratory failure due to lung restriction is the best indication of
      mechanical ventilation. The results in COPD are questionable. Whatever to the
      technique of ventilation and the underlying disease, the pneumologist has to
      ascertain the steady state of the medical condition, patient and family
      education, and social situation, all factors to be taken into account before the
      patient can be discharged. Knowing the specific needs in these patients'care, the
      pneumologist plays a key role at each stage of home return and follow-up. He co
      ordinates the different aspects of pneumological care, like rehabilitation and
      acute episodes treatment. The overall care of the patients should be improved by
      the development of health networks in the field of chronic respiratory
      insufficiency.

PMID- 11468589
TI  - [Effects of a pressure support ventilation of 6 cm H2O on oxygen consumption of
      the respiratory muscles during weaning of mechanical ventilation].
AB  - OBJECTIVE: To determine the effects of a pressure support ventilation (PSV) of 6
      cm H(2)O during spontaneous breathing on oxygen consumption of the respiratory
      muscles (VO(2) resp), gas exchange, respiratory rate, tidal volume and to
      determine if these low levels of PSV can reduce or cancel the increase in work of
      breathing induced by the resistances of the endotracheal tube and the circuit of
      the respirator. PATIENTS AND METHODS: Prospective study. Twenty intubated
      patients were studied. The VO(2) resp was assessed by measurements of inspired
      and expired concentrations of oxygen (O(2)) and carbon dioxide (CO(2)) in
      patients during controlled ventilation and spontaneous breathing. Gas exchange,
      respiratory rate, minute ventilation, tidal volume and VO(2) resp were collected
      during spontaneous breathing with a PSV level of 6 cm H(2)O and without PSV.
      SETTING: Respiratory Intensive Care Unit, Amiens, University Hospital 80054
      Amiens. RESULTS: A PSV level of 6 cm H(2)O significantly increased the
      spontaneous tidal volume (+12%) without any modification in respiratory rate,
      minute ventilation, tidal volume and gas exchange. No significant improvement in
      VO(2) resp was found when a PSV level of 6 cm H(2)O was added. CONCLUSION:
      Despite a significant increase in spontaneous tidal volume, adding a PSV level of
      6 cm H(2)O did not improve VO(2) resp. Thus, low level of PSV did not reduce the
      increased work of breathing induced by the resistances of the ventilator tubing
      and the endotracheal tube.

PMID- 11468590
TI  - [Is aggressiveness really inhibited in asthmatic adolescents? An epidemiological
      approach].
AB  - Clinical data support the hypothesis that aggressivity is inhibited amongst
      asthmatics. The relationship of violence, as a marker of aggressiveness, to
      asthma was examined in a population-based sample of 12.466 students of secondary
      schools in France (Enquete sur la Sante de l'adolescent 1993/1994) using an
      epidemiological questionnaire on health status, life events, potential risk
      factors and disease management. Twelve percent of the students reported having
      had at least one episode of asthma, 4% had asthma attacks, and 1% had severe
      asthma at the time of the survey. Asthma had been confirmed by a physician in 81%
      of the cases. Acts of violence [fits of violence (21%), screaming when angry
      (30%), hitting when angry (45%), 'racketeering' (1%)] or sustained violence
      [physical aggressions (15%) and rape (4%)] were significantly related to asthma
      in past year when applying a logistic model including age, sex, ethnic group,
      socioeconomical status, geographical zone, and type of school as potential
      confounders (adjusted odds-ratios ranging from 1.26 to 1.87 and from 1.44 to 3.48
      respectively). Similarly, violence was related to severe asthma. Results
      persisted after exclusion of individuals for whom asthma had not been confirmed
      by a physician. These findings strongly challenge the current hypothesis
      according to which aggressiveness is inhibited in asthmatic adolescents.

PMID- 11468591
TI  - [Contribution of bronchial fibroscopy in pneumonology services in developing
      countries].
AB  - Bronchial fibroscopy is a recent investigation method that requires equipment and
      facilities difficult to implement in respiratory diseases units in developing
      countries. In Burkina Faso, this technique was introduced for the first time in
      February 1997. The purpose of this study was to determine the contribution of
      bronchial fibroscopy for the diagnosis of respiratory disease in countries with
      limited resources. This study was conducted between February 1997 and October
      1998 at the respiratory diseases unit of the Yalgado Ouedraogo National Hospital
      Center in Ouagadougou, Burkina Faso. Thirty-five cases of tuberculosis were
      diagnosed, including 29 cases with bronchial node involvement, where bronchial
      fibroscopy is an essential diagnostic examination, and 6 cases of
      bacteriologically proven pulmonary tuberculosis. Ten cases of lung cancer were
      diagnosed (40% squamous cell carcinoma). Malignant disease is a reality in
      developing countries despite low rates of diagnosis due to insufficient
      diagnostic facilities. For tuberculosis, the importance of specific treatment is
      certainly well established and should always be initiated, even if fibroscopy
      cannot be performed. This contrasts with the situation for malignant disease,
      where the high prevalence of lung cancer (9.9% of the bronchial fibroscopies
      performed) is associated with total lack of treatment due to the absence of a
      thoracic surgery unit or a radiotherapy unit, and the impossibility of providing
      satisfactory surveillance of anti-cancer chemotherapy.

PMID- 11468592
TI  - [Parietal thoracic tuberculosis in the absence of immunosuppression by HIV
      infection].
AB  - Parietal thoracic abscess formation of a tuberculous nature is a rare form of
      extrapulmonary tuberculosis, usually described in cases of severe tuberculosis
      encountered in HIV-infected patients. We report 13 cases of parietal tuberculosis
      in patients without HIV infection who were investigated between October 1988 and
      December 1999. During this period, we cared for 2 663 patients with tuberculosis.
      The series included 9 women and 4 men age 17 to 60 years, mean age 39 years. The
      clinical aspect of the parietal abscess was variable. Cold fluctuating abscess
      was dominant in 10 cases. In 3 cases, the parietal abscess had a hard consistence
      simulating a malignant tumor. The parietal abscess was in a posteriosuperior or
      posteriobasal location in 4 cases, and in an anterosuperior, anterobasal or
      axillary location in 6. Multiple thoracic abscesses were observed in only 3
      cases. The size of the abscess varied from 2 to 2.5 cm. Radiologically, rib
      damage was present in 4 cases, scapular damage in 1, with bone lysis in 3 cases.
      Other localizations of tuberculosis were observed in 4 cases. one patient had
      multiple peripheral node enlargement, another had parenchymal lung damage and a
      third had a vertebral localization. Culture of abscess pus provided the diagnosis
      in 10 cases. the diagnosis was confirmed by pathology in 8 cases on a biopsy of
      the abscess border. Anti-tuberculosis drugs allowed successful recovery in all
      patients. We analyzed the clinical aspects of cold thoracic abscesses and discuss
      differential diagnosis. Early diagnosis and treatment is essential.

PMID- 11468593
TI  - [Localized benign pleural mesothelioma observed at the Dakar University
      Hospital].
AB  - We report two cases of localized benign pleural mesothelioma with different
      clinical features. Neuropsychiatric symptoms, including coma, hemiplegia,
      seizures and misbehavior predominated in the first case, associated with
      hypoglycemia. The symptoms in the second case were essentially respiratory
      (cough, dyspnea, and chest pain). Treatment consisted in thoracotomy and complete
      surgical resection. Histopathology revealed fusiform cells and collagen stroma.
      These two cases illustrate the diversity of clinical expression of benign
      localized pleural mesothelioma and confirm their complete resolution after
      surgical treatment.

PMID- 11468594
TI  - [Pulmonary mucormycosis: benefit of aerosol amphotericin B?].
AB  - Mucormycosis is an opportunistic fungal infection usually observed in diabetic or
      neutropenic patients. Prognosis is serious with a high rate of mortality.
      Intravenous amphotericin B is the gold standard treatment. The main side effect
      is renal failure. Liposomal amphotericin B (AmBisome(R)) is not nephrotoxic and
      can be proposed as an alternative treatment although its cost is high. We report
      a case of mucormycosis in a diabetic woman who developed renal failure after
      intravenous amphotericin B treatment. AmBisome(R) could not be used for long-term
      treatment due to its high case. The patient was given nebulized amphotericin B
      and achieved recovery. This kind of treatment may provide a useful alternative to
      intravenous amphotericin B.

PMID- 11468595
TI  - [Primary pulmonary myxoid liposarcoma discovered fortuitously].
AB  - We report a fortuitous discovery of primary pulmonary myxoid liposarcoma in an
      HIV-positive patient. Primary pulmonary localizations are uncommon. Generally,
      pulmonary localizations are metastatic. There is a male predominance and
      diagnosis is generally made around 40 years of age. The two main features of
      liposarcoma are the large tumor size and the complex histology that evolves over
      time. Pathology findings are rarely reproducible and vary from one pathologist to
      another. Macroscopically, liposarcomas can mimic benign tumors. The risk of
      recurrence is high after simple enucleation due to microscopic extracapsular
      extensions. Surgery remains the predominant treatment. Wide complete excision, if
      possible, provides long-term survival.

PMID- 11468596
TI  - [Malignant primary fibrous histiocytoma of the pleura].
AB  - Malignant fibrous histiocytoma (MFH) is a uncommon primary sarcoma, occurring
      exceptionally in the thoracic site. We report a case of malignant fibrous
      histiocytoma of the pleura in a 23-year-old man. The tumour was revealed by chest
      pain and alteration of the general state. A complete resection of the tumour
      histologically diagnosed as a malignant fibrous histiocytoma, with a right upper
      lobectomy was performed. No adjuvant treatment was proposed. The patient died 4
      months after operation with cerebral metastasis. CONCLUSION: MFH should be
      treated by wide surgical resection if technically feasible, the role of adjuvant
      treatment is not defined.

PMID- 11468597
TI  - [Endobronchial localization of Launois Bensaude syndrome].
AB  - Launois Bensaude syndrome is a benign, asymetric lipomatosis involving the upper
      back, shoulders, neck and arms. The disorder is usually asymptomatic although
      mediastinal lipomas, extrinsic compression of trachea, obstructive sleep apnea
      syndrome have been described. We report for the first time to our knowledge a
      case of Launois Bensaude syndrome with bronchial submucosal adiposis infiltration
      presenting as flask, smooth, begnin tumor like formation involving several
      bronchi. Whether this submucosal adipose infiltration participate to the
      obstructive syndrome is discussed.

PMID- 11468598
TI  - [Pleural sarcoidosis. Course of an unusual localization after corticosteroid
      treatment].
AB  - We report the case of a 69-year-old woman investigated for suspected
      pleuropneumopathy. Thoracoscopy led to the diagnosis of sarcoidosis with pleural
      involvement. This case illustrates an uncommon localization of sarcoidosis and
      its clinical course after corticosteroid treatment.

PMID- 11468599
TI  - [Transcranial Doppler: an underused technique in respiratory disease for the
      diagnosis of right-left shunts].

PMID- 11468600
TI  - [Bronchogenic dissemination of a pulmonary hydatid cyst].

PMID- 11468601
TI  - Screening for lung cancer.

PMID- 11468602
TI  - Oral balsalazide (Colazal) for ulcerative colitis.

PMID- 11468603
TI  - Botulinum toxin for cervical dystonia.

PMID- 11468604
TI  - A randomized, controlled trial of a simple emergency department intervention to
      improve the rate of primary care follow-up for patients with acute asthma
      exacerbations.
AB  - STUDY OBJECTIVE: We determined whether a simple emergency department intervention
      improves the likelihood of primary care provider (PCP) follow-up after ED
      discharge for an acute asthma exacerbation. METHODS: This randomized, controlled
      clinical trial was conducted in an urban university-based ED. Participants were
      patients with asthma between the ages of 16 and 45 years who were treated and
      discharged from the ED. The study intervention was usual care or an intervention
      that consisted of a free 5-day course of prednisone, vouchers for transportation
      to and from their PCP, and a 48-hour telephone reminder to make an appointment
      with their PCP. The main outcome was whether the patient received follow-up care
      as determined by PCP contact at 4 weeks. RESULTS: One hundred ninety-two patients
      with asthma were enrolled over 8 months; 178 (93%) had complete follow-up. The
      intervention and control groups were similar with regard to age, sex, ethnicity,
      or years of education. The 2 groups were also comparable with respect to multiple
      measures of baseline access/barriers to care and severity of ED exacerbation.
      Patients receiving the intervention were significantly more likely to follow up
      with their PCP than control patients (relative risk 1.6; 95% confidence interval
      [CI] 1.1, 2.4). When adjusted for other factors influencing PCP follow-up care
      (ethnicity, prior PCP relationship, insurance status, regular car access),
      intervention patients were more likely to follow up with their PCP (odds ratio
      3.1; 95% CI 1.5, 6.3). CONCLUSION: Providing medication, transportation vouchers,
      and a telephone reminder to make an appointment increased the likelihood that
      discharged patients with asthma obtained PCP follow-up.

PMID- 11468605
TI  - Differences between men and women in reporting of symptoms during an asthma
      exacerbation.
AB  - STUDY OBJECTIVE: Compared with men, women presenting to the emergency department
      with acute asthma are more likely to be admitted and to have a longer hospital
      stay. This study compares peak expiratory flow rate (PEFR) with reported symptom
      severity between men and women with acute asthma. The null hypothesis was that
      men and women report similar severity symptoms for similar levels of airway
      obstruction. METHODS: This study combined data from 4 prospective cohort studies
      performed from 1996 to 1998 as part of the Multicenter Airway Research
      Collaboration. Using a standardized protocol, investigators at 64 EDs in 21 US
      states and 4 Canadian provinces provided 24-hour per day coverage for a median of
      2 weeks. RESULTS: Of the 1,291 patients with moderate to severe exacerbations
      (initial percentage of predicted PEFR <80%), 62% were women. Women were more
      likely than men to report "severe" complaints in terms of symptom frequency,
      symptom intensity, and resulting activity limitations (all P <.05). Women with
      moderate exacerbations were especially likely to describe their exacerbation as
      causing "severe" activity limitations (sex-PEFR interaction, P =.05). CONCLUSION:
      Men are less likely than women to report severe asthma symptoms and activity
      limitations in the presence of airway obstruction. This finding supports use of
      objective measures of airway obstruction when managing patients with asthma so
      that those whose symptoms do not reflect the severity of their obstruction can be
      recognized and properly treated. It also reconfirms the need for increased
      research on differences between men and women in acute asthma.

PMID- 11468606
TI  - Efficacy of eye patching for traumatic corneal abrasions: a controlled clinical
      trial.
AB  - STUDY OBJECTIVE: We sought to evaluate the efficacy of eye patching in the
      treatment of traumatic corneal abrasions in terms of time to healing and
      reduction in pain and discomfort. METHODS: One hundred sixty-three patients
      presenting at the emergency department of a large university-affiliated hospital
      with traumatic corneal abrasions were included in this single-blind prospective
      controlled trial. Eligible patients were assigned to 1 of 2 treatment regimens:
      topical antibiotic ointment and occlusive patch over the affected eye (n=82) or
      topical antibiotic ointment 4 times a day without an occlusive patch (n=81).
      Patients were reexamined every 24 hours until corneal healing occurred. Healing
      evaluation was performed by the emergency physician, using a slit lamp with
      fluorescein staining, without knowledge of the patient's assignment to a
      treatment group. The degree of discomfort was assessed at each visit by using a
      visual analog scale. RESULTS: Both treatment groups were similar regarding size
      of the corneal lesions, delay from trauma to first ED visit, presence of foreign
      body or siderosis, initial degree of discomfort, and presence of specific
      symptoms (irritation, foreign body sensation, photophobia, redness, and pain). In
      the patched group, cumulative incidences of healing were 51%, 78%, and 92% after
      1, 2, and 3 days, respectively, compared with 60%, 83%, and 88% in the nonpatched
      group. In the patched group, symptoms of initial discomfort decreased by 4.8,
      4.1, and 5.5 cm after 1, 2, and 3 days, respectively, compared with 3.3, 5.1, and
      6.5 cm in the nonpatched group. CONCLUSION: Eye patching does not appear to be
      beneficial in the treatment of traumatic corneal abrasions compared with topical
      antibiotic ointment.

PMID- 11468607
TI  - Comparison of the auditory and visual privacy of emergency department treatment
      areas with curtains versus those with solid walls.
AB  - STUDY OBJECTIVE: The design and function of emergency departments may allow
      breaches of privacy that could adversely affect patient satisfaction and medical
      care. We sought to determine whether patients perceive less privacy in ED
      treatment areas with curtains than in rooms with solid walls. METHODS: Patients
      18 years and older at a university hospital ED who received care in a room with
      solid walls and a door, a curtained area next to the nurses' station, or a
      curtained area away from the nurses' station were surveyed. Patients responded on
      a 5-point Likert scale to 11 questions regarding privacy. Differences between
      areas were determined by using the Kruskal-Wallis and Mann-Whitney tests and were
      considered significant at P values of less than.05. RESULTS: Structured
      interviews were conducted with 108 ED patients. Responses from those in the
      curtained areas were similar. Compared with those in the rooms with walls, these
      patients more often believed that they could overhear others and that others
      could hear them, view them, hear personal information, and view personal parts of
      their bodies (P < or =.04 for all). They also perceived a lower overall sense of
      privacy (P <.01). Of all those surveyed, 85.2% reported "a lot of" or "complete"
      respect for privacy by the staff, and 92.6% experienced at least as much privacy
      as they expected, with no difference between areas. CONCLUSION: Patients perceive
      significantly less auditory and visual privacy in ED treatment areas with
      curtains compared with a room with solid walls. Consideration of these findings
      in current practice and in future ED design and construction is suggested.

PMID- 11468608
TI  - Factors associated with older patients' satisfaction with care in an inner-city
      emergency department.
AB  - STUDY OBJECTIVES: We sought to assess older patients' satisfaction with care in
      the emergency department and to identify factors associated with global
      satisfaction with care. METHODS: We performed a prospective cohort study of 778
      patients 65 years of age and older presenting to an urban academic ED between
      1995 and 1996, of whom 79% were black and 63% were female. A baseline survey at
      presentation to the ED asked for demographic information, medical history, and
      health-related quality of life information. A follow-up satisfaction survey asked
      patients to rate the care they received in the ED on a 5-point Likert scale
      (1=excellent, 5=poor). Overall satisfaction with care, dichotomized into
      responses of "excellent" versus all others, was the primary dependent variable in
      our bivariate analyses. RESULTS: Of respondents, 40% rated their ED care as
      "excellent." Variables significantly correlated with high satisfaction include
      having the perception of time spent in the ED as not "too long," having the
      emergency physicians and nurses clearly answer patients' questions, having a
      relationship of trust with an ED staff member, being told why tests were done,
      feeling involved in decisions about care as much as they wanted, having pain
      addressed fully, having a perception of greater health status, and having fewer
      comorbid conditions at the time of the ED visit. Results may be applicable only
      to urban academic EDs and may be limited by time elapsed between ED visits and
      follow-up surveys. CONCLUSION: To improve quality of care for older adults in the
      ED, physicians should be more attentive to older patients' concerns and
      questions, recognize and aggressively treat pain, and reduce the patients'
      perception of a long waiting time.

PMID- 11468609
TI  - Work interrupted: a comparison of workplace interruptions in emergency
      departments and primary care offices.
AB  - STUDY OBJECTIVE: We sought to determine the number of interruptions and to
      characterize tasks performed in emergency departments compared with those
      performed in primary care offices. METHODS: We conducted an observational time
      motion, task-analysis study in 5 nonteaching community hospitals and 22 primary
      care offices in 5 central Indiana cities. Twenty-two emergency physicians and 22
      office-based primary care physicians (PCPs) were observed at work. The number of
      interruptions, tasks, simultaneous tasks, and patients concurrently managed were
      recorded in 1-minute increments during 150- to 210-minute observation periods.
      RESULTS: Emergency physicians were interrupted an average of 9.7 times per hour
      compared with 3.9 times per hour for PCPs, for an average difference of 5.8 times
      per hour (95% confidence interval [CI] 4.2 to 7.4). PCPs spent an average of 11.4
      minutes per hour performing simultaneous tasks compared with 6.4 minutes per hour
      for emergency physicians (average difference, 5.0 minutes; 95% CI 1.2 to 8.8).
      Emergency physicians spent an average of 37.5 minutes per hour managing 3 or more
      patients concurrently compared with 0.9 minutes per hour for PCPs. PCPs spent
      significantly more time performing direct patient care, and emergency physicians
      spent significantly more time in analyzing data, charting, and taking reports on
      patients. CONCLUSION: Emergency physicians experienced more interruptions and
      managed more patients concurrently than PCPs. PCPs spent more time performing
      simultaneous tasks than emergency physicians. Our study suggests there are
      important ergonomic differences between emergency medicine and office-based
      primary care work environments that may require different training approaches,
      design considerations, and coping strategies.

PMID- 11468610
TI  - The effect of working serial night shifts on the cognitive functioning of
      emergency physicians.
AB  - STUDY OBJECTIVE: We sought to determine whether working 5 serial night shifts in
      the emergency department results in a decline in physician performance as
      measured with an intelligence test. METHODS: This study compared the cognitive
      functioning of emergency physicians who worked the day shift (7 AM to 5 pm) with
      those who worked 5 consecutive night shifts (11 pm to 7 am). The Fluid Scale of
      the Kaufman Adolescent and Adult Intelligence Test (KAIT) was administered to 16
      emergency medicine residents. Half of the residents (group A) were tested while
      working day shifts, and the other half (group B) were tested after working 5
      consecutive night shifts. After a minimum interval of 2 months, the residents
      were retested in reverse order, with group A tested after working night shifts
      and group B tested while working day shifts. RESULTS: A total of 16 emergency
      medicine residents were tested. A paired t test was used to determine whether day
      shift KAIT scores are different from night-shift KAIT scores. The mean day-shift
      KAIT score was 119.1 (SD=7.7), and the mean night-shift KAIT score was 107.2
      (SD=10.2). This difference was significant (mean difference=11.9; 95% confidence
      interval 7.0 to 16.8; P <.001), with the day-shift scores being statistically
      higher than the night-shift scores. CONCLUSION: Working a series of 5 night
      shifts results in a substantial decline in cognitive performance in physicians
      working in the ED.

PMID- 11468611
TI  - Ovarian torsion: a fifteen-year review.
AB  - STUDY OBJECTIVE: Our purpose was to describe the history, physical, and
      laboratory findings in women with ovarian torsion (OT). METHODS: A retrospective
      chart review was conducted at 2 urban teaching hospitals. All women admitted from
      1984 to 1999 with surgically proven OT were included in the study. RESULTS: The
      87 women ranged in age from 14 to 82 years (mean 32 years). Twelve were pregnant,
      15 were postmenopausal, and 7 were posthysterectomy. Thirty-five (40%) had prior
      pelvic surgery; 18 of these (21% of the total) had undergone tubal ligation.
      Twenty-two (25%) women had a history of an ovarian cyst. Sixty-five (75%)
      patients were seen in the emergency department. Pain characteristics were
      variable: the onset was sudden in 51 (59%); "sharp" or stabbing in 61 (70%); and
      radiated to the flank, back, or groin in 44 (51%) patients. Only 3 had peritoneal
      signs at presentation. The majority of patients (70%) had nausea or vomiting.
      Fever was rare (2 patients). OT was considered in the admitting differential
      diagnosis in 41 (47%) patients. An enlarged ovary (>5 cm) was found in 77 (89%)
      patients at surgery. Only 26 patients had surgery within 24 hours. In 8 (9%)
      patients, detorsion was possible; of these, 3 had surgery within 24 hours.
      CONCLUSION: The diagnosis of OT is often missed and ovarian salvage is rare. Pain
      characteristics are variable and objective findings are uncommon in OT.

PMID- 11468612
TI  - The Canadian CT Head Rule Study for patients with minor head injury: rationale,
      objectives, and methodology for phase I (derivation).
AB  - Head injuries are among the most common types of trauma seen in North American
      emergency departments, with an estimated 1 million cases seen annually. "Minor"
      head injury (sometimes known as "mild") is defined by a history of loss of
      consciousness, amnesia, or disorientation in a patient who is conscious and
      talking, that is, with a Glasgow Coma Scale score of 13 to 15. Although most
      patients with minor head injury can be discharged without sequelae after a period
      of observation, in a small proportion, their neurologic condition deteriorates
      and requires neurosurgical intervention for intracranial hematoma. The objective
      of the Canadian CT Head Rule Study is to develop an accurate and reliable
      decision rule for the use of computed tomography (CT) in patients with minor head
      injury. Such a decision rule would allow physicians to be more selective in their
      use of CT without compromising care of patients with minor head injury. This
      paper describes in detail the rationale, objectives, and methodology for Phase I
      of the study in which the decision rule was derived. [Stiell IG, Lesiuk H, Wells
      GA, McKnight RD, Brison R, Clement C, Eisenhauer MA, Greenberg GH, MacPhail I,
      Reardon M, Worthington J, Verbeek R, Rowe B, Cass D, Dreyer J, Holroyd B,
      Morrison L, Schull M, Laupacis A, for the Canadian CT Head and C-Spine Study
      Group. The Canadian CT Head Rule Study for patients with minor head injury:
      rationale, objectives, and methodology for phase I (derivation). Ann Emerg Med.
      August 2001;38:160-169.]

PMID- 11468613
TI  - A current concept of trauma-induced multiorgan failure.
AB  - Trauma deaths continue to show a trimodal distribution: immediately at the scene,
      within the first 24 hours during initial resuscitation, and in the next 3 to 4
      weeks as a result of multiple organ failure.(1) Failure to resuscitate adequately
      in the emergency department can lead to acidosis, hypothermia, and coagulopathy,
      which can result in multiple organ failure and cause death in these patients. Our
      current understanding of the initial response to shock and trauma and the
      development of the systemic inflammatory response syndrome and progressive organ
      failure is one of a continuum initiated and perpetuated by inflammation and
      inflammatory mediators. The pathophysiologic character, diagnosis, prevention,
      and treatment of traumatic injury-induced multiple organ failure are discussed.

PMID- 11468614
TI  - Cervical pregnancy: a case report.
AB  - This is a case report of an uncommon but dangerous form of ectopic pregnancy. The
      incidence of cervical pregnancy may be increasing, and it should be included in
      the differential diagnosis of vaginal bleeding in pregnancy. Included in this
      case report are discussions of the incidence, causes, predisposing factors,
      diagnostics, and treatment options.

PMID- 11468615
TI  - Crash Injury Research and Engineering Network (CIREN): an update.

PMID- 11468616
TI  - Today's CIREN: news you can use.

PMID- 11468617
TI  - Food for thought.

PMID- 11468619
TI  - Electrocardiographic diagnosis of myocardial infarction.

PMID- 11468621
TI  - Filming of emergency department patients.

PMID- 11468622
TI  - My field of dreams.

PMID- 11468623
TI  - More NPs are the answer for nonurgent ED patients.

PMID- 11468625
TI  - A 39-year-old man with an overdose of beta-blockers.

PMID- 11468626
TI  - Adequacy of pain assessment and pain relief and correlation of patient
      satisfaction in 68 ED fast-track patients.
AB  - INTRODUCTION: The new standards of the joint commission on accreditation of
      healthcare organizations specify the patient's right to appropriate assessment
      and management of pain. With this impetus, we looked at our own practice to see
      how well we assess and manage patients with pain. METHODS: Patients who presented
      with minor nonemergent pain were interviewed on arrival, and then again before
      discharge, with use of a structured questionnaire. A total of 68 completed pain
      surveys were analyzed. RESULTS: With use of a visual analog scale, patients rated
      their pain on arrival and at discharge; they also rated pain they were willing to
      accept when it was time for discharge. Sixty percent of the patients went home
      with more pain than they were willing to accept. Fifty-one percent of the
      patients were offered something for pain, and only half of them said the pain
      relief was adequate. The median time from arrival to administration of pain
      medication was 104 minutes. Surprisingly, the median patient satisfaction rating
      for overall care was "very good." DISCUSSION: This survey revealed that acute
      pain conditions are underevaluated and undertreated in one fast-track setting,
      suggesting that ED staff need more education about the management of acute pain.
      It also showed that relying on patient satisfaction surveys as surrogate markers
      for how well we manage pain is erroneous.

PMID- 11468627
TI  - Is routine heparin lock placement beneficial in the evaluation and treatment of
      febrile children?
AB  - INTRODUCTION: Nurses often use intravenous heparin locks (HL) with pediatric
      patients while obtaining laboratory studies to evaluate fever without a source.
      The purpose of the HL is to avoid an intramuscular injection if parenteral
      antibiotics are subsequently ordered. The objectives of this study were to
      determine if HL placement in patients undergoing laboratory evaluation for fever
      without a source (1) results in fewer injections and (2) is associated with
      increased use of antibiotics. METHODS: A retrospective chart review of ED
      patients aged 3 to 36 months was performed. Patients included in the review had
      fever with no identified source of infection, and a complete blood cell count
      and/or blood culture had been ordered. For analysis, patients who received an HL
      were compared with patients who did not receive an HL. RESULTS: A total of 439
      patients had laboratory studies for fever without a source, with 345 (79%) in the
      HL group. No statistically significant differences were found in antibiotic
      administration, number of needle sticks, age, temperature, or white blood cell
      count between the groups. DISCUSSION: The use of an HL in young febrile ED
      patients did not change the total number of needle sticks or the likelihood of
      antibiotic administration.

PMID- 11468628
TI  - Characteristics of the trauma recidivist: an exploratory descriptive study.
AB  - INTRODUCTION: The purpose of this study was to identify characteristics and
      perceptions of trauma recidivists. Information obtained from this study will help
      health care professionals better understand trauma patients and design more
      effective trauma prevention programs. METHODS: An exploratory descriptive,
      correlational design was used. A convenience sample of 100 trauma patients
      entering a midwestern university medical center were studied. A demographic chart
      review and a personal interview consisting of 29 questions were conducted for
      each subject. The interview questions sought information regarding high-risk
      behavior, risk-taking personality traits, safety precautions used, and social,
      psychological, and environmental factors surrounding the patient's traumatic
      event. RESULTS: Thirty-six percent of trauma patients studied were recidivists.
      The recidivist was more likely to be male, younger than 45 years, a member of a
      racial minority, single, uninsured, and have less than 12 years of education.
      Behavioral characteristics common to most recidivists included a history of past
      arrests, illegal drug use, and having witnessed past violent injuries.
      DISCUSSION: Trauma remains one of the most devastating diseases facing americans.
      Characteristics of trauma recidivists have been identified, and further research
      is needed to test possible interventions to curb the unnecessary trauma injuries
      that occur every day.

PMID- 11468630
TI  - Pediatric emergency preparedness in schools: a report from the 2001 Southeastern
      Regional EMSC annual meeting.

PMID- 11468631
TI  - Pedestrian safety--teaching points and resources for ED nurses educating the
      community.

PMID- 11468632
TI  - EMTALA: practical application with an algorithm.

PMID- 11468633
TI  - It can happen to you: the firsthand accounts of six nurses accused of and
      disciplined for professional misconduct.

PMID- 11468634
TI  - The PAWS program: Pediatric Animal Awareness and Safety.

PMID- 11468635
TI  - The nursing shortage--a Washington Post columnist's perspective. Interview by
      Iris C. Frank.

PMID- 11468636
TI  - A staffed ED assessment room: impact on wait times for nonurgent patients at a
      Saudi Arabian hospital.

PMID- 11468637
TI  - Evidentiary examination without a police report: should it be done? Are delayed
      reporters and nonreporters unique?

PMID- 11468638
TI  - Methylprednisolone in acute spinal cord injury: fact or fantasy?

PMID- 11468639
TI  - A 26-year-old woman with right shoulder pain.

PMID- 11468640
TI  - Barrett's esophagus.

PMID- 11468642
TI  - Toaster convergence.

PMID- 11468643
TI  - Investigating the determinants of decreasing postmyocardial infarction mortality:
      an analysis of in-hospital data from 1992 and 1997.
AB  - BACKGROUND: Although acute myocardial infarction (AMI) is the leading cause of
      mortality in the industrialized world, postmyocardial infarction mortality rates
      have been declining in recent decades. Two possible contributing factors toward
      this encouraging trend include changing patient characteristics and improved
      patient management. OBJECTIVES: To compare temporal changes in the
      characteristics and management of patients with AMI at a tertiary care hospital
      (Sunnybrook and Women's College Health Sciences Centre) in Toronto, Ontario.
      METHODS: Two hundred hospital charts of patients with AMI as the most responsible
      diagnosis were reviewed (100 from 1992 and 100 from 1997). One hundred thirty
      prespecified variables were extracted from each chart, with emphasis placed on
      baseline clinical characteristics, AMI management and survival. RESULTS: Between
      1992 and 1997, AMI in-hospital mortality declined from 20% to 15%. Most baseline
      clinical characteristics (age, sex, comorbidity, cardiac history, and presenting
      symptoms and signs) were similar across the 1992 and 1997 patient populations.
      The only significant risk factor change involved an increase in the prevalence of
      hypercholesterolemia. In contrast, between 1992 and 1997 there was an increased
      in-hospital use of anticoagulants, antiplatelets, thrombolytics, beta-blockers,
      angiotensin-converting enzyme inhibitors and statins. Similarly, there was an
      increased use of coronary angioplasty and coronary bypass surgery. There was no
      significant change in the use of AMI therapies that are potentially harmful,
      including antiarrythmic agents and calcium channel blockers. CONCLUSIONS: AMI
      patient characteristics were similar between 1992 and 1997 but there were
      striking changes in AMI treatment patterns. The increased use of evidence-based
      pharmacotherapy may be the most significant contributing factor to declining
      postmyocardial infarction mortality.

PMID- 11468644
TI  - Tumour necrosis factor-alpha soluble receptors type I are related to symptoms and
      left ventricular function in hypertrophic cardiomyopathy.
AB  - BACKGROUND: High circulating levels of tumour necrosis factor-alpha (TNF-alpha)
      and its soluble receptors (sTNFRI, sTNFRII) are involved in the pathogenesis of
      congestive heart failure due to left ventricular (LV) systolic dysfunction.
      However, their role in hypertrophic cardiomyopathy (HCM) has not been elucidated.
      OBJECTIVES: To determine the circulating serum levels of sTNFRI in a wide
      spectrum of patients with HCM, and to study in detail their relationship with
      symptom severity and various echocardiographic disease characteristics. PATIENTS
      AND METHODS: sTNFRI serum levels were measured in 66 patients with HCM and 30 age
      matched healthy subjects using enzyme linked immunosorbent assay for serum levels
      of soluble TNF-a receptor type I at rest and at 1, 3 (sTNFRI-3e) and 6 h after
      dobutamine stress echocardiography (DSE). RESULTS: sTNFRI-r levels were
      significantly higher in patients with HCM than in control subjects (2.8+/-0.8
      compared with 1.4+/-0.5 ng/mL, P<0.002). In patients with HCM, there was a
      significant difference in sTNFRI-r levels between mildly (New York Heart
      Association [NYHA] functional class I and II) and severely (NYHA functional class
      III and IV) symptomatic patients (1.4+/-0.9 compared with 4.8+/-1.0 ng/mL,
      p<0.001). Higher sTNFRI-r and sTNFRI-3e levels were found in patients with an LV
      restrictive filling pattern during DSE compared with sustained abnormal
      relaxation (p<0.052, p<0.004, respectively), and in patients with reduced
      compared with normal increments in LV fractional shortening during DSE (p<0.02,
      p<0.003, respectively). CONCLUSIONS: Significant differences in sTNFRI serum
      levels between patients with HCM and healthy subjects were shown. In patients
      with HCM, sTNFRI levels were higher in severely symptomatic patients, and in
      patients with reduced LV systolic and diastolic reserve during DSE. These data
      suggest that TNF may be involved in the pathogenesis of HCM.

PMID- 11468645
TI  - A comparison of quantitative coronary angiography systems using a unique set of
      in vivo coronary stenosis images.
AB  - OBJECTIVE: To compare the accuracy and precision of measurements of minimum lumen
      diameter (MLD) among two existing, and one new, quantitative coronary angiography
      systems. MATERIALS AND METHODS: The analysis was performed using in vivo
      cinearteriograms of precisely drilled, radiolucent plastic beads that were
      inserted percutaneously into the coronary arteries of canines. The existing
      algorithms compared were the ArTrek and the Coronary Measurement System (CMS).
      The latter was applied in two modes: a mode based on a minimal cost analysis
      algorithm and a mode based on a gradient field transform. The new algorithm
      (CorTrek) was also applied in two modes: a mode called the ArTrek compatible mode
      and a mode known as the 'regression' mode. The latter mode uses a look-up table,
      based on a phantom calibration step, to readjust the measured MLD to overcome
      system nonlinearities (overestimation of small diameters and underestimation of
      large diameters). RESULTS: In the absence of editing, the optimal accuracy (no
      significant bias) was achieved with the ArTrek compatible algorithm (-0.03 mm for
      an MLD between 0.83 and 1.83 mm). All other algorithms showed significant under-
      or overestimation of the MLD within this range. The precision ranged from 0.18 to
      0.40 mm without editing, and was best with the ArTrek algorithm. CONCLUSIONS: The
      present study provides in vivo validation and comparative performance
      characteristics of a new, accurate coronary quantitative angiography system.

PMID- 11468646
TI  - The relationship of insulin resistance measured by reliable indexes to coronary
      artery disease risk factors and outcomes--a systematic review.
AB  - OBJECTIVES: To provide a qualitative and quantitative review of the published
      literature that examines the relationship between reliable markers of insulin
      resistance and coronary artery disease risk factors (plasma glucose,
      triglycerides, high density lipoprotein cholesterol, hypertension, obesity, low
      density lipoprotein size) and outcomes (as related to ischemic heart disease) in
      populations with and without type 2 diabetes. METHODS: The MEDLINE database was
      searched (January 1966 to April 2000). Additional references were identified from
      bibliographies of retrieved articles. The quantitative relationship between
      insulin resistance and coronary artery disease outcomes was estimated in
      individual studies by derivation of 2x2 tables. RESULTS: Of 780 publications
      reviewed, 28 met the inclusion criteria. Twenty publications investigated the
      relationship of insulin resistance markers with coronary artery disease risk
      factor profiles only, while eight publications primarily evaluated coronary
      artery disease outcomes. CONCLUSIONS: The present review suggests that
      populations with lower insulin resistance measured by reliable indexes are
      consistently associated with better overall cardiovascular risk profiles
      (including reduced clustering of risk factors), and improved coronary artery
      disease outcomes than populations with elevated insulin resistance.

PMID- 11468647
TI  - Direct drainage of the right pulmonary veins into the coronary sinus with intact
      interatrial septum: a case report.
AB  - Partial anomalous pulmonary venous connection to the coronary sinus is rare. This
      anomaly is even more rare in the absence of interatrial communication. Usually,
      the anomalous right pulmonary veins drain to the right atrium or venae cavae,
      while the anomalous left veins connect to the coronary sinus or left innominate
      vein. The present report is the first in the English literature to document a
      situs solitus case in which all three right pulmonary veins drained directly into
      the coronary sinus without an atrial septal defect. Closure of the coronary sinus
      orifice and unroofing of the coronary sinus into the left atrium is a safe and
      effective way of treating this anomaly.

PMID- 11468648
TI  - Pericarditis presenting and treated as an acute anteroseptal myocardial
      infarction.
AB  - Early recognition and treatment of acute myocardial infarctions have been
      accepted as improving patient mortality. With the popular use of thrombolytic
      therapy, it is necessary to rule out contraindications and to consider other
      causes for ST segment elevation. A unique patient experiencing chest pain with
      marked and localized ST segment elevation in the anteroseptal leads is presented.
      He was treated with thrombolytic therapy. Subsequent investigations ruled out the
      diagnosis of myocardial infarction and confirmed the diagnosis of pericarditis.
      Although the patient's outcome was uncomplicated, physicians are urged to
      consider the diagnosis of pericarditis before using thrombolytic therapy to avoid
      life-threatening complications.

PMID- 11468650
TI  - [We, brazilian physician].

PMID- 11468659
TI  - [What is a terminally ill patient?].

PMID- 11468661
TI  - [How do to appraise falls in aged].

PMID- 11468660
TI  - [Endometrial thickening in climacteric: How to investigate ].

PMID- 11468662
TI  - [How do to recognize post traumatic abdominal compartment syndrome].

PMID- 11468663
TI  - [Is bronchopneumonia with pneumatocele and pleural effusion pathognomic of
      staphylococcus?].

PMID- 11468664
TI  - [Stomach neoplasm and metastasis. To operate?].

PMID- 11468665
TI  - [Hospitalization, is necessary in pregnancy hypertensive syndrome?].

PMID- 11468673
TI  - [Patient advocacy and legislation].

PMID- 11468674
TI  - [Surgical videolaparoscopic treatment of gastroesophageal reflux disease:
      modified Nissen technique - functional results].

PMID- 11468675
TI  - [A matter of language].

PMID- 11468676
TI  - [Fetal medicine: obstetric specialty?].

PMID- 11468677
TI  - [Reliability study of the Brazilian version of a structured interview for the
      diagnosis of dementia].
AB  - OBJECTIVES: to evaluate the reliability of the Structured Interwiew for the
      Diagnosis of Alzheimer's Type Dementia, Multi-Infarct Dementia and Dementia of
      other Aetiology (SIDAM) Portuguese version; validated as a reliable instrument to
      be applied to patients with a presumed diagnosis of dementia or mild cognitive
      impairment. METHODS: twenty elderly patients of our Service with a clinical
      diagnosis of dementia were interviewed simultaneously by the authors, utilizing
      the SIDAM's Portuguese version. The answers were noted down concomitantly, and
      then compared. The reliable evaluation of the diagnosis of the SIDAM's Portuguese
      version was based on Kappa's statistics (K). RESULTS: of the patients studied,
      ten were women; with an average age of 75.5 years. Nine were maried, two were not
      and nine widowers. They had attended school for about 5.3 years. The average
      score on the Mini Mental State was 16.8. As to their professional activities, 12
      (60%) were manual workers, eight were not. Everyone had the diagnosis of
      dementia, being most of them, Alzheimer's Type. The concordance rate between ICD
      10, DSM III-R and the SIDAM's questions showed a K > 0.87; and between the
      interviewers, rarely K < 0.87. CONCLUSION: K >/= 0.87 suggests that the Brazilian
      version of SIDAM can be considered a reliable instrument to be applied to
      outpatients with presumed diagnosis of dementia in Brazil.

PMID- 11468678
TI  - [Clinical variables of preoperative risk].
AB  - BACKGROUND: To identify risk variables leading to early postoperative pulmonary
      complication (POPC) in thoracic and upper abdominal surgery. METHODS: 297
      patients submitted to elective surgery were classified as low, moderate and high
      risk for POPC using PORT scale, following Torrington & Henderson (1988). The
      patients were followed up for 72 hours postoperative. POPC were defined as
      atelectasis, pneumonia, tracheobronchitis, wheezing, prolonged intubation and/or
      prolonged mechanical ventilation. Univariate analysis was applied to study these
      independent variables: type of surgery, age, nutritional status (BMI),
      respiratory disease, smoking habit, spirometry and surgical time. Multivariate
      logistic regression analysis were performed in order to evaluate the relationship
      between independent and dependent (POPC) variables. RESULTS: POPC incidence was
      12.1%. By multivariate logistic regression analysis the variables increasing
      chance to POPC was cough with yellow mucus (OR= 3.8), thoracic surgery (OR=2.9)
      compared to abdominal surgery, BMI (OR=1.13), duration of smoking (OR=1.03) and
      prolonged duration of surgery (OR=1.007). In the thoracic surgery group,
      multivariate logistic regression analysis showed: wheezing (OR=6.2), BMI
      (OR=1.15), long time smoking (OR= 1.04) and prolonged duration of surgery (OR=
      1.007) related to POPC. CONCLUSION: The variables occurrence that increased
      chance to POPC in thoracic and upper abdominal surgery were: cough with yellow
      mucus, thoracic surgery, BMI, duration of smoking and duration of surgery.
      Regarding the thoracic surgery group the significance variables were wheezing,
      BMI, duration of smoking and duration of surgery.

PMID- 11468679
TI  - [Isolated ileocecal tuberculosis simulating malignant neoplasia and Crohn's
      disease].
AB  - BACKGROUND: Isolated ileocecal involvement by tuberculosis in the absence of
      pulmonar disease is rare in Brasil, therefore causes a diagnostic dilemma as it
      mimics colonic malignancy and Crohn's disease. METHODS: Between 1969 and 1989,
      eight patients with isolated hypertrophic ileocecal tuberculosis were treated by
      surgery in the Gastroenterology Surgery Department of the HSPE-FMO. The most
      common complaint among them was abdominal pain (100%) with associated symptoms of
      weight loss (62.5%); nausea, vomiting, fever and general weekness appeared in
      half of the patients. A right iliac fossa mass was present in seven (87.5% ) of
      them. The mean duration of symptoms was 14.7 month (range 5-36 months). In all
      eight patients chest x-rays were negative for tuberculosis. Barium contrast
      studies showed abnormalities in all cases, but these could not be distinguished
      from carcinoma. Colonoscopy was helpful in establishing the diagnosis of
      suboclusive lesions of the ileocecal regions in three patients. Tuberculosis
      diagnosis was suspected in two of them because ofr the presence of granulomas in
      colonic biopsy material. RESULTS: Six patients were submitted to elective right
      hemicolectomy. The two remaining with suspect of tuberculosis were operated with
      signals of intestinal occlusion, and underwent a limited ileocaecal resection.
      The positive diagnosis of intestinal tuberculosis was made in all the patients by
      identification of acid-fast bacilli and by the presence of caseating granulomas
      in intestinal or lymph node tissue on histological examination. The outcome in
      all of them was favorable. They received treatment with three antituberculosis
      drugs over a twelve month period. CONCLUSION: Hypertrophic ileocecal tuberculosis
      must still be considered in the differential diagnosis of abdominal pathology
      localized in the right lower quadrant.

PMID- 11468680
TI  - [Pulmonary involvement in children with AIDS: clinical study and necropsy of 14
      cases].
AB  - BACKGROUND: To describe clinical, laboratorial, radiological, and
      histopathological lung findings from necroscopy of aidetic children with
      pulmonary disease. MATERIAL AND METHODS: Fourteen children admitted at the
      Hospital Universitario Antonio Pedro - Universidade Federal Fluminense, Niteroi,
      RJ, and Instituto de Puericultura e Pediatria Martagao Gesteira - Universidade
      Federal do Rio de Janeiro, Rio de Janeiro, RJ, between 1989 and 1996, were
      revised in a retrospective survey. RESULTS: Eight were males (57%). The median
      age was 1.2 years old (from three months to nine years). Nine children (64.4%)
      were younger than 24 months old. The HIV transmission was vertical in 10 (71%)
      children. In these cases, five mothers were contaminated from heterosexual
      relations. Pneumonia (n=8), oral candidiasis (n=8), and diarrhea (n=5) were the
      most common previous conditions. The most frequent signs and symptoms on
      admission were fever (n=12), respiratory distress (n=10), cough (n=10),
      peripheral lymphadenopathy (n=11), hepatomegaly and/or splenomegaly (n=10), and
      malnutrition (n=9). The chest x-rays findings were condensation (n=5) and diffuse
      infiltrates (n=6) patterns. The microscopic lung characteristics were compatibles
      with pneumonia by cytomegalovirus (CMV) (n=9), bacteria (n=8), Pneumocystis
      carinii (n=3), Toxoplasma gondii (n=1), Hystoplasma capsulatum (n=1) and
      Lymphocytic interstitial pneumonia (n=1). The association between CMV and
      bacteria was observed in six cases. CONCLUSIONS: Age less than two years old,
      vertical transmission, inespecific clinical presentation of pneumonia, and
      infiltrates and condensation patterns at the x-rays were the predominant
      characteristics. Cytomegalovirus and bacteria were the most common etiologic
      agents, being their association frequent. Lymphocytic interstitial pneumonia and
      pneumonia by P. carinii were not common causes of pulmonary disease.

PMID- 11468681
TI  - [Nutritional status of children and teenagers with chronic renal failure].
AB  - BACKGROUND: the purpose of this study is to evaluate the nutritional status of
      children and teenagers with chronic renal (CRF) failure using anthropometric
      measurements. MATERIAL AND METHODS: 41 children and adolescents with (CRF)
      (creatinine "clearance" < 50 ml/min/1,73m(2)) followed at the Pediatric
      Nephrology Unit (HC-UNICAMP), between January 1995 and November 1996, were
      evaluated by the assessment of anthropometric measurements, mid upper arm
      circunference (MUAC) and triceps skinfold (TSF). With these measurements, mid arm
      fat area (MUAFA) and arm muscle area (AMA) were calculated and its z-scores.
      These measurements were performed twice at least, ranging from 0.21 to 1.3 years
      (0.88 +/- 0.04). RESULTS: all the z-scores (MUAC, TSF, MUAFA and AMA) were very
      low, and only the AMA z-score was statistically significant (p= 0,03 Wilcoxon
      test). The patients were divided in to groups, according to their treatment, and
      the MAC z-score for the renal transplantation group was statistically significant
      (p= 0,02 Wilcoxon test). CONCLUSIONS: these data demonstrate a compromised
      nutritional status from both muscle and fat stores, with an improvement in muscle
      stores.

PMID- 11468682
TI  - [Videolaparoscopic surgical treatment of gastroesophageal reflux disease:
      modified Nissen technique - clinical and functional results].
AB  - BACKGROUND: Gastroesophageal reflux disease is highly common worldwide and
      surgical treatment is being indicated more frequently. Currently, laparoscopic is
      the access of choice and several antireflux techniques may be used. We prefer a
      modified Nissen technique. PURPOSE: To analyze preoperative clinical and
      functional parameters and compare with postoperative outcome of a modified valve
      technique performed by laparoscopy. METHODS: A group of 59 patients underwent
      laparoscopic modified Nissen valve. Preoperative diagnosis was made by
      radiological contrast exams and endoscopy in all patients. Esophagus manometry
      was performed in 35 patients and scintigraphy scan in 15 patients. Complicated
      esophagitis occurred in 54.2%, with 21 (35.6%) patients presenting a Barrett's
      epithelium. Laparoscopic surgery was performed in all patients with no conversion
      to open surgery, with an average time of 123.9 minutes. RESULTS: There were no
      intraoperative complications. Hospital discharge occurred in an average of 47.6
      hours. Symptoms as dysphagia, pain, regurgitation and flatus occurred in 48.1% of
      the patients in the first thirty days. Average follow-up was 20.8 months.
      Postoperative radiological, endoscopic, manometric and scintigrafic scan exams
      showed a significant improvement, as well as clinical assessment using Visick's
      classification, which showed excellent and good results in 93.1% of the patients.
      CONCLUSION: Comparative analysis of clinical assessment and exam results lad us
      to conclude that modified Nissen surgery by laparoscopic access corrects
      gastroesophageal reflux in most patients followed-up.

PMID- 11468683
TI  - [University hospitals: past, present and future].
AB  - PURPOSE: This article discusses the evolution of university hospitals, their
      characteristics, functioning and financing and their role in medical education
      and research. METHODS: Data come from a workshop organized by the World Health
      Organization on university hospitals in 22 countries. RESULTS: The main finding
      is that these institutions are increasingly inadequate to the reality of the
      health sector in which they operate and to the challenges posed by the profound
      changes currently taking place in the health system of most countries.
      CONCLUSION: A reform is needed, and the article presents a few possible
      strategies for reforming these hospitals.

PMID- 11468684
TI  - [Frequency of digestive symptoms in Brazilian patients with Diabetes Mellitus].
AB  - PURPOSE: To determine the frequencies of digestive symptoms in an unselected
      sample of Brazilian diabetics, in comparison to those verified in the general
      population. METHODS: The frequencies of 13 digestive symptoms were determined in
      153 type 1 and type 2 diabetics and in 50 apparently healthy controls, utilizing
      a structured, standardized questionnaire. RESULTS: The percentage of diabetics
      with at least one symptom was significantly higher than in controls (70% vs 36%,
      p = 0.01). Higher frequencies of upper digestive symptoms, such as postprandial
      epigastric fullness (30% vs 35%), heartburn (30% vs 34%), as well as constipation
      (17% vs 12%) were observed in both groups. Nevertheless, only the prevalence of
      dysphagia (13% vs 2%) was significantly increased (p = 0.02) in diabetics.
      CONCLUSION: These findings indicate that gastrointestinal symptoms are common in
      diabetics, but this seems also to be the case in the general population, with the
      exception of dysphagia. The frequencies of symptoms observed in Brazil were
      similar to those reported in studies from the North Hemisphere, a finding that
      does not support the hypothesis that external factors may influence the
      prevalence of gastrointestinal symptoms in diabetics.

PMID- 11468685
TI  - [Transferring the evidence from clinical research to cardiologic practice].

PMID- 11468686
TI  - Pseudoexon activation as a novel mechanism for disease resulting in atypical
      growth-hormone insensitivity.
AB  - Inherited growth-hormone insensitivity (GHI) is a heterogeneous disorder that is
      often caused by mutations in the coding exons or flanking intronic sequences of
      the growth-hormone receptor gene (GHR). Here we describe a novel point mutation,
      in four children with GHI, that leads to activation of an intronic pseudoexon
      resulting in inclusion of an additional 108 nt between exons 6 and 7 in the
      majority of GHR transcripts. This mutation lies within the pseudoexon (A(-1)-->G(
      1) at the 5' pseudoexon splice site) and, under in vitro splicing conditions,
      results in inclusion of the mutant pseudoexon, whereas the wild-type pseudoexon
      is skipped. The presence of the pseudoexon results in inclusion of an additional
      36-amino acid sequence in a region of the receptor known to be involved in homo
      dimerization, which is essential for signal transduction.

PMID- 11468687
TI  - Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas
      suggests different genetic mechanisms for pathogenesis of TSC lesions.
AB  - Tuberous sclerosis complex (TSC), an autosomal dominant disease caused by
      mutations in either TSC1 or TSC2, is characterized by the development of
      hamartomas in a variety of organs. Concordant with the tumor-suppressor model,
      loss of heterozygosity (LOH) is known to occur in these hamartomas at loci of
      both TSC1 and TSC2. LOH has been documented in renal angiomyolipomas (AMLs), but
      loss of the wild-type allele in cortical tubers appears to be very uncommon.
      Analysis of second, somatic events in tumors for which the status of both TSC1
      and TSC2 is known is essential for exploration of the pathogenesis of TSC-lesion
      development. We analyzed 24 hamartomas from 10 patients for second-hit mutations,
      by several methods, including LOH, scanning of all exons of both TSC1 and TSC2,
      promoter methylation of TSC2, and clonality analysis. Our results document loss
      of the wild-type allele in six of seven AMLs, without evidence of the
      inactivation of the second allele in many of the other lesions, including tumors
      that appear to be clonally derived. Laser-capture microdissection further
      demonstrated loss of the second allele in all three cellular components of an
      AML. This study thus provides evidence that, in both TSC1 and TSC2, somatic
      mutations resulting in the loss of wild-type alleles may not be necessary in some
      tumor types-and that other mechanisms may contribute to tumorigenesis in this
      setting.

PMID- 11468688
TI  - Mapping of autosomal dominant osteopetrosis type II (Albers-Schonberg disease) to
      chromosome 16p13.3.
AB  - The osteopetroses are a heterogeneous group of conditions characterized by a bone
      density increase due to impaired bone resorption. As well as the two or more
      autosomal recessive types, two autosomal dominant forms of osteopetrosis,
      differentiated by clinical and radiological signs, are described. Autosomal
      dominant osteopetrosis (ADO) type II, also known as "Albers-Schonberg disease,"
      is characterized by sclerosis, predominantly involving the spine (vertebral end
      plate thickening, or Rugger-Jersey spine), the pelvis ("bone-within-bone"
      structures), and the skull base. An increased fracture rate can be observed in
      these patients. By linkage analysis, the presence, on chromosome 1p21, of a gene
      causing ADO type II was previously suggested. However, analysis of further
      families with ADO type II indicated genetic heterogeneity within ADO type II,
      with the chromosome 1p21 locus being only a minor locus. We now perform a
      genomewide linkage scan of a French extended family with ADO type II, which
      allows us to localize an ADO type II gene on chromosome 16p13.3. Analysis of
      microsatellite markers in five further families with ADO type II could not
      exclude this chromosomal region. A summed maximum LOD score of 12.70 was
      generated with marker D16S3027, at a recombination fraction (straight theta) of
      0. On the basis of the key recombinants in the families, a candidate region of
      8.4 cM could be delineated, flanked by marker D16S521, on distal side, and marker
      D16S423, on the proximal side. Surprisingly, one of the families analyzed is the
      Danish family previously suggested to have linkage to chromosome 1p21. Linkage to
      chromosome 16p13.3 clearly cannot be excluded in this family, since a maximum LOD
      score of 4.21 at theta=0 is generated with marker D16S3027. Because at present no
      other family with ADO type II has proved to have linkage to chromosome 1p21, we
      consider the most likely localization of the disease-causing gene in this family
      to be to chromosome 16p13.3. This thus reopens the possibility that ADO type II
      is genetically homogeneous because of a single gene on chromosome 16p13.3.

PMID- 11468689
TI  - MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer
      mice, is mutated in autosomal dominant nonsyndromic hearing loss.
AB  - Mutations in the unconventional myosin VI gene, Myo6, are associated with
      deafness and vestibular dysfunction in the Snell's waltzer (sv) mouse. The
      corresponding human gene, MYO6, is located on chromosome 6q13. We describe the
      mapping of a new deafness locus, DFNA22, on chromosome 6q13 in a family affected
      by a nonsyndromic dominant form of deafness (NSAD), and the subsequent
      identification of a missense mutation in the MYO6 gene in all members of the
      family with hearing loss.

PMID- 11468690
TI  - Molecular characterization and gene content of breakpoint boundaries in patients
      with neurofibromatosis type 1 with 17q11.2 microdeletions.
AB  - Homologous recombination between poorly characterized regions flanking the NF1
      locus causes the constitutional loss of approximately 1.5 Mb from 17q11.2
      covering > or =11 genes in 5%-20% of patients with neurofibromatosis type 1
      (NF1). To elucidate the extent of microheterogeneity at the deletion boundaries,
      we used single-copy DNA fragments from the extreme ends of the deleted segment to
      perform FISH on metaphase chromosomes from eight patients with NF1 who had large
      deletions. In six patients, these probes were deleted, suggesting that breakage
      and fusions occurred within the adjacent highly homologous sequences.
      Reexamination of the deleted region revealed two novel functional genes FLJ12735
      (AK022797) and KIAA0653-related (WI-12393 and AJ314647), the latter of which is
      located closest to the distal boundary and is partially duplicated. We defined
      the complete reading frames for these genes and two expressed-sequence tag (EST)
      clusters that were reported elsewhere and are associated with the markers SHGC
      2390 and WI-9521. Hybrid cell lines carrying only the deleted chromosome 17 were
      generated from two patients and used to identify the fusion sequences by junction
      specific PCRs. The proximal breakpoints were found between positions 125279 and
      125479 in one patient and within 4 kb of position 143000 on BAC R-271K11
      (AC005562) in three patients, and the distal breakpoints were found at the
      precise homologous position on R-640N20 (AC023278). The interstitial 17q11.2
      microdeletion arises from unequal crossover between two highly homologous WI
      12393-derived 60-kb duplicons separated by approximately 1.5 Mb. Since patients
      with the NF1 large-deletion syndrome have a significantly increased risk of
      neurofibroma development and mental retardation, hemizygosity for genes from the
      deleted region around the neurofibromin locus (CYTOR4, FLJ12735, FLJ22729,
      HSA272195 (centaurin-alpha2), NF1, OMGP, EVI2A, EVI2B, WI-9521, HSA272196, HCA66,
      KIAA0160, and WI-12393) may contribute to the severe phenotype of these patients.

PMID- 11468691
TI  - The present and future of molecular diagnostics.

PMID- 11468692
TI  - Molecular detection of breast cancer markers.

PMID- 11468693
TI  - Transcriptional complementarity in breast cancer: application to detection of
      circulating tumor cells.
AB  - BACKGROUND: We used a combination of genetic subtraction, silicon DNA microarray
      analysis, and quantitative PCR to identify tissue- and tumor-specific genes as
      diagnostic targets for breast cancer. METHODS AND RESULTS: From a large number of
      candidate antigens, several specific subsets of genes were identified that showed
      concordant and complementary expression profiles. Whereas transcriptional
      profiling of mammaglobin resulted in the detection of 70% of tumors in a panel of
      46 primary and metastatic breast cancers, the inclusion of three additional
      markers resulted in detection of all 46 specimens. Immunomagnetic epithelial cell
      enrichment of circulating tumor cells from the peripheral blood of patients with
      metastatic breast cancer, coupled with RT-PCR-based amplification of breast tumor
      specific transcripts, resulted in the detection of anchorage-independent tumor
      cells in the majority of patients with breast cancer with known metastatic
      disease. CONCLUSION: Complementation of mammaglobin with three additional genes
      in RT-PCR increases the detection of breast cancers in tissue and circulating
      tumor cells.

PMID- 11468694
TI  - Molecular cytogenetic analysis of glial tumors using spectral karyotyping and
      comparative genomic hybridization.
AB  - BACKGROUND: Glial tumors are the most common tumors of the central nervous
      system, affecting individuals of all ages. Conventional cytogenetics have been
      unable to identify a consistent chromosomal translocation or rearrangement in
      this group of tumors; thus, more advanced molecular cytogenetic approaches are
      required. METHODS AND RESULTS: In this study, 16 glial tumors, including two
      recurrences and six glioma cell lines, were analyzed by spectral karyotyping
      (SKY) and comparative genomic hybridization (CGH). From 169 rearrangements
      detected by SKY, chromosomes 1 and 10 were the most frequently affected by
      translocation (18 of 169 and 16 of 169 rearrangements, respectively). Other
      frequently altered chromosomes included chromosomes 3 (13 of 169 rearrangements),
      5 (ten of 169 rearrangements), 7 (ten of 169 rearrangements ), and 11 (ten of 169
      rearrangements). A clustering of centromeric breakpoints was detected in
      chromosomes 3, 5, 10, 11, 16, 17, and 20. CGH analysis identified consistent gain
      of part or all of chromosome 7 among the 10 astrocytic tumors (five of ten
      specimens) in the study group. Analysis of the three gangliogliomas and one
      ependymoma identified a much simpler pattern of primarily numerical change.
      CONCLUSION: Application of improved cytogenetic methods can increase our
      abilities to progress toward effective strategies of molecular diagnosis and
      classification of glial tumors.

PMID- 11468695
TI  - Pleomorphic (giant and/or spindle cell) carcinoma of lung shows a high percentage
      of variant CYP1A12.
AB  - BACKGROUND: Pleomorphic carcinoma (PC) of the lung is an aggressive epithelial
      neoplasm composed of giant and/or spindle tumor cells and associated with short
      survival. Most patients are cigarette smokers. The tumor susceptibility gene P
      450 1A1 (CYP1A1) is involved in the activation of polycyclic aromatic
      hydrocarbons, including benzo[a]pyrene, producing DNA-damaging epoxides that lead
      to G:C-->T:A point mutations. Isoleucine (Ile)-valine (Val) and Val-Val genotypes
      of the CYP1A1 exon 7 polymorphism are associated with an increased risk for lung
      cancer in certain populations. METHODS AND RESULTS: We sought to determine
      whether 25 archival, formalin-fixed, paraffin-embedded PC samples had a modified
      CYP1A1 gene profile at exon 7 using allele-specific PCR amplification. KRAS
      mutation status was available for all samples. Previous investigations have shown
      0.88 Ile-Ile, 0.12 Ile-Val, and rarely, Val-Val as normal baseline population
      frequencies. Conversely, the markedly different PC CYP1A1 population frequencies
      were more likely to have the heterozygote variant alleles: 0.24 (six cases, Ile
      Ile) and 0.76 (19 cases, Ile-Val; P <.001). CYP1A1 genotypes were found to be
      similar in both tumor and nontumor samples in a given case. All KRAS-mutated
      cases were Ile-Val heterozygotes. CONCLUSION: The increased propensity for the
      variant CYP1A1 allele may be the contributing factor to PC pathogenesis and may
      also result from KRAS mutations in these tumors.

PMID- 11468696
TI  - A PCR assay for detecting clonal rearrangement of the TCR-gamma gene.
AB  - BACKGROUND: The T-cell receptor gamma chain (TCR-gamma) gene has 11 functional
      variable (V) exons that can be organized into four subfamilies and four
      functional joining (J) exons that can be divided into two subfamilies. METHOD AND
      RESULTS: Three multiplex PCR reactions amplifying the TCR-gamma gene were
      developed. Primer combinations for multiplex PCR were chosen so that the V-region
      subfamily and J-region subfamily involved in a clonal band could be identified.
      Control primers from the protease inhibitor (PI) gene were also included in each
      reaction to verify the presence of amplifiable DNA. Fifty-six archived samples
      that had been tested by Southern blot for clonal rearrangement of the TCR-beta
      gene were analyzed with the TCR-gamma PCR protocol. Twenty-one of 56 samples were
      TCR-beta positive by Southern blot and thus expected to be positive with TCR
      gamma PCR. Thirty-five of 56 samples were TCR-beta negative by Southern blot. Of
      these, 14 samples showed clonal rearrangement of the immunoglobulin heavy chain
      gene. The TCR-gamma PCR protocol showed a diagnostic sensitivity for detecting T
      lineage clonality of 90%, with a diagnostic specificity for detecting T-cell
      lineage of only 74%. CONCLUSION: The PCR protocol described here performed well
      in comparison with a TCR-beta Southern protocol.

PMID- 11468697
TI  - Improved detection of viral RNA isolated from liquid-based cytology samples.
AB  - BACKGROUND: Molecular diagnosis requires the ability to obtain high-quality
      nucleic acids that are representative of the disease state. We evaluated the
      recovery and detection of limiting amounts of viral oncogenic RNA from cells
      fixed in liquid-based cytology media. METHODS AND RESULTS: Serial dilutions of a
      human papillomavirus (HPV)-positive cell line fixed in a liquid media was used as
      a model system. Total nucleic acid (TNA) extraction produced RNA with clearly
      visible ribosomal bands even after one year of storage. These TNA extracts,
      treated with DNase-I, were used in an RT-PCR assay for HPV-16 E6-E7 oncogenic
      transcripts. With chemiluminscent Southern blot detection, samples with one HPV
      positive cell in 30,000 were consistently detected. CONCLUSION: PreservCyt-fixed
      cells can yield RNA suitable for molecular assays even after one year of storage.

PMID- 11468698
TI  - Solid-phase amplification and detection: a single-tube diagnostic assay for
      infectious agents.
AB  - BACKGROUND: We report the development of an enzyme-linked immunosorbent assay
      like single-tube assay for the detection of infectious agents in a microtiter
      tray format. METHODS AND RESULTS: The method, sequential nucleic acid
      amplification and capture (SNAAC), combines amplification with hybridization of
      the product to a surface/matrix-bound oligonucleotide probe. After amplification
      of the target sequence using species-specific primers, one of which contains a
      detection tag such as fluorescein or biotin, a denaturation and hybridization
      cycle is performed. This allows capture by an oligonucleotide that is covalently
      bound to the surface of a microtiter tray well or other support. After washing to
      remove unincorporated solution-phase oligonucleotide bearing the detection tag,
      the level of captured product is determined through a colorimetric reaction using
      an automated plate reader. We show the value and utility of the SNAAC detection
      method using cloned sequences of the important human respiratory pathogen
      Chlamydia pneumoniae. CONCLUSIONS: SNAAC is a simple, rapid, and inexpensive
      method for the detection of low levels of infectious agents that is readily
      adaptable to current clinical laboratory equipment, thus avoiding the need to
      develop or purchase new instrumentation.

PMID- 11468699
TI  - Two rare confounding polymorphisms proximal to the factor V Leiden mutation.
AB  - BACKGROUND: Comprehensive assessment of thrombophilia risk includes
      characterization of the R506Q (Leiden) mutation in factor V in many patients.
      Although activated protein C resistance is often assessed by means of a
      coagulation test, molecular interrogation of the G1691A mutation provides
      confirmation and interpretive utility in patients undergoing anticoagulation.
      Many molecular methods are available to provide genotyping at this locus. Among
      these, PCR-restriction fragment length polymorphism (RFLP) is widely used.
      Unfortunately, because this common mutation is 11 bp from the 3' end of exon 10,
      one PCR primer often anneals within intron 10. As a consequence, polymorphism can
      confound test results. METHOD AND RESULTS: In the course of a clinical diagnostic
      test of 15,301 patients, two samples repeatedly showed two different unusual
      electrophoretic mobilities after PCR and restriction enzyme digestion. After
      stripping patient identifiers and entering a research protocol, the amplicons
      from these DNAs were sequenced in parallel with normal and heterozygous G1691A
      control genomic DNA samples. This sequencing showed two novel polymorphisms, each
      mapping to intron 10. CONCLUSION: PCR-RFLP-based methods rely on sequence
      conservation in the interrogated region. Amplification of mutated loci adjacent
      to introns present a special risk for confounding restriction patterns.
      Sequencing amplicons with reproducibly unusual restriction patterns resolved the
      paradoxical restriction pattern in this case.

PMID- 11468700
TI  - Ramification amplification: a novel isothermal DNA amplification method.
AB  - We have developed a novel isothermal DNA amplification method with an
      amplification mechanism quite different from conventional PCR. This method uses a
      specially designed circular probe (C-probe) in which the 3' and 5' ends are
      brought together in juxtaposition by hybridization to a target. The two ends are
      then covalently linked by a T4 DNA ligase in a target-dependent manner, producing
      a closed DNA circle. In the presence of an excess of primers (forward and reverse
      primers), a DNA polymerase extends the bound forward primer along the C-probe and
      displaces the downstream strand, generating a multimeric single-stranded DNA
      (ssDNA), analogous to the "rolling circle" replication of bacteriophages in vivo.
      This multimeric ssDNA then serves as a template for multiple reverse primers to
      hybridize, extend, and displace downstream DNA, generating a large ramified
      (branching) DNA complex. This ramification process continues until all ssDNAs
      become double-stranded, resulting in an exponential amplification that
      distinguishes itself from the previously described nonexponential rolling circle
      amplification. In this report, we prove the principle of ramification
      amplification. By using a unique bacteriophage DNA polymerase, O29 DNA
      Polymerase, that has an intrinsic high processivity, we are able to achieve
      significant amplification within 1 hour at 35 degrees C. In addition, we applied
      this technique for in situ detection of Epstein-Barr viral sequences in Raji
      cells.

PMID- 11468701
TI  - Clinical news update.

PMID- 11468721
TI  - Pseudotypes of vesicular stomatitis virus-bearing envelope antigens of certain
      HIV-1 strains permissively infect human syncytiotrophoblasts cultured in vitro:
      implications for in vivo infection of syncytiotrophoblasts by cell-free HIV-1.
AB  - Intrauterine infection of the fetus is clearly an important mode of vertical
      transmission of human immunodeficiency virus type 1 (HIV-1). The
      syncytiotrophoblast layer of the human placenta must be traversed by HIV-1 in
      order to reach underlying cells and fetal capillaries. Although HIV-1 has been
      detected in the syncytiotrophoblast layer in situ, there is conflicting evidence
      regarding infection of syncytiotrophoblast cells with cell-free virus. The
      phenotypic mixing between HIV-1 and vesicular stomatitis virus (VSV) has been
      exploited to assay the susceptibility of human term syncytiotrophoblast cells to
      penetration by various strains of HIV-1. VSV(HIV-1(IIIB)) and VSV(HIV-1(Ba-L))
      pseudotypes were found to enter syncytiotrophoblast cells. In contrast, VSV
      pseudotyped with envelope glycoproteins of RF, MN, or Ada-M strains of HIV-1 did
      not infect syncytiotrophoblasts. Plating efficiency of VSV(HIV-1(IIIB)) and
      VSV(HIV-1(Ba-L)) was 10-fold lower on syncytiotrophoblasts than on T-cells and
      macrophages, respectively. Incubation of VSV(HIV-1(IIIB)) and VSV(HIV-1(Ba-L))
      viruses with appropriate HIV-1 neutralizing sera before infection strongly
      inhibited entry of pseudotyped VSV into syncytiotrophoblast cells. These findings
      demonstrated that infection of syncytiotrophoblasts with VSV(HIV-1) pseudotypes
      was mediated by Env from IIIB and Ba-L strains of HIV-1. Monoclonal antibodies
      (MAb) to CD4, CXCR4, CCR5, and CCR3 were tested for their ability to block
      VSV(HIV-1) infection of syncytiotrophoblast cells. Neither the anti-CD4 nor the
      anti-CXCR4, anti-CCR5, and anti-CCR3 MAb had any inhibitory effect on infection
      of syncytiotrophoblast cells with VSV(HIV-1) pseudotypes. Results from this study
      suggest that cell-free HIV-1 can enter syncytiotrophoblasts and the
      susceptibility of these cells to penetration by the virus is strain dependent.
      Pseudotype infection merely demonstrates that the first steps in HIV-1
      replication are possible in syncytiotrophoblast cells.

PMID- 11468722
TI  - Lack of effect of chemokine receptor CCR2b gene polymorphism (64I) on HIV-1
      plasma RNA viral load and immune activation among HIV-1 seropositive female
      workers in Abidjan, Cote d'Ivoire.
AB  - The prevalence of the CCR2b-V64I mutation among human immunodeficiency virus
      (HIV)-seropositive and -seronegative female workers and the potential effect of
      heterozygosity of this mutation on HIV-1 plasma RNA viral load and markers of
      immune activation were assessed. CCR2b-V64I was detected by polymerase chain
      reaction, followed by restriction enzymes analysis; plasma viral load was
      measured by the Amplicor HIV-1 monitor assay and CD4(+) T-cell counts and markers
      of immune activation by standard three-color FACscan flow cytometry. Of the 260
      female workers, 56 (21.5%) were heterozygous for CCR2b-V64I, and 8 (3%) were
      homozygous. Of the 99 HIV-seronegative female workers, 19 (19.2%) were
      heterozygous for the CCR2b-V64I mutation compared with 37 (23%) of the 161 HIV
      seropositive FSW (P = 0.47). In a univariate analysis of viral load among HIV
      seropositive FSW, no difference was noted between those heterozygous for or
      without the mutation; both groups had plasma viral loads of 5.0 log(10)
      copies/ml. After controlling for the effects of CD4(+) T-cell counts in a
      multivariate analysis, no significant difference was observed between the groups
      in viral load or in markers of immune activation. The data suggest that the
      presence of the CCR2b mutation has no effect on HIV-1 plasma viral load and
      markers of immune activation in our study population. The finding that the
      frequency of this mutation is similar in HIV-seropositive and -seronegative
      female workers suggests that its presence is not associated with increased risk
      of HIV infection.

PMID- 11468723
TI  - Experimental hepatitis A virus infection in guinea pigs.
AB  - Although many of the properties of hepatitis A virus (HAV) are known, several
      aspects of HAV pathogenesis are still not understood, such as the mechanism
      underlying the hepatotropism or HAV replication in extrahepatic sites. Detailed
      studies of these aspects were hampered mostly by the lack of accessible animal
      models, since only nonhuman primates are susceptible to experimental infections.
      An alternative animal model would also be of interest to assess the primary
      replication site and for the evaluation of the safety and efficacy of vaccines. A
      study was undertaken to determine whether HAV can infect guinea pigs and whether
      they are useful as a model for studying aspects of HAV pathogenesis and for the
      evaluation of vaccines. HAV variants adapted to primate or guinea pig tissue
      culture were used to inoculate guinea pigs intraperitoneally and by the oral
      route. The animals were observed for clinical disease, shedding of HAV in stools,
      viremia, seroconversion, evidence for liver damage by biochemical liver function
      tests, virus presence in the liver, development of hepatic histopathological
      changes, and occurrence of HAV in extrahepatic organs. The animals developed an
      active, clinically inapparent infection with specific histopathological changes
      in the liver. Although virus replication occurred, as shown by RT-PCR and
      isolation of infectious virus from feces and serum, it seems unlikely that guinea
      pigs are suitable for studying the clinical features of hepatitis A, because the
      clinical and laboratory parameters remained normal. However, guinea pigs appear
      useful for studying some aspects of HAV pathogenesis and for testing the safety
      of vaccines.

PMID- 11468724
TI  - State of HBV DNA in HBsAg-negative, anti-HCV-positive hepatocellular carcinoma:
      existence of HBV DNA possibly as nonintegrated form with analysis by Alu-HBV DNA
      PCR and conventional HBV PCR.
AB  - The role of hepatitis B virus (HBV) in carcinogenesis of hepatitis B surface
      antigen (HBsAg)-negative, anti-hepatitis C virus (anti-HCV)-positive
      hepatocellular carcinoma (HCC) remains unknown. To investigate the state of HBV
      DNA in such HCC, HBV DNA was examined by polymerase chain reaction (PCR) between
      HBV DNA and human Alu sequence (HBV-Alu PCR), which could detect integrated form
      of HBV DNA only, and by conventional HBV PCR, which could detect both integrated
      and episomal forms of HBV DNA. In all the 17 HBsAg-positive HCC, HBV DNA was
      detected by both HBV-Alu PCR method and conventional HBV PCR method. By contrast,
      in HBsAg-negative, anti-HCV-positive cases, HBV DNA was detected in 10 of 21
      (47.6%) by conventional HBV PCR and in none of 21 (0%) by HBV-Alu PCR method.
      Thus, integrated form of HBV DNA was not found in most HbsAg-negative, anti-HCV
      positive HCC in the current study. The role of episomal form of HBV DNA requires
      further investigation of its involvement in the process of the development of
      HBsAg-negative, anti-HCV-positive HCC.

PMID- 11468725
TI  - Subcellular localisation of the X protein in HBV infected hepatocytes.
AB  - Hepatitis B virus X protein (HBx) is a multifunctional protein that exerts its
      effects primarily by acting as a transcriptional transactivator of viral and
      multiple host cell genes. HBx is thought to be essential for maintaining viral
      replication and has been implicated in the development of hepatocellular
      carcinoma in patients chronically infected with hepatitis B virus. Very little is
      known about its functional mechanisms and although interactions with several
      nuclear and cytoplasmic proteins have been demonstrated in vitro, there is no
      clear consensus as to where HBx localises in infected hepatocytes. In this study,
      the expression and intracellular distribution of HBx were examined in human liver
      biopsies using an anti-HBx rabbit polyclonal antiserum. HBx was detected in a
      high proportion (69%) of samples from patients with chronic HBV infection.
      Detection of HBx correlated with the absence of cirrhosis and the presence of
      serum e-antigen. HBx was detected predominantly in the cytoplasm; however, it was
      also found in the nuclei of up to 20% of positively stained hepatocytes, either
      exclusively nuclear or localised both in the nucleus and cytoplasm within the
      same cell. Furthermore, the intracellular distribution of HBx was analysed in
      transfected Huh-7 cells by confocal microscopy, using the monoclonal antibody
      16F1. In these experiments, a substantial nuclear detection was confirmed in a
      significant proportion of HBx expressing cells. The data indicate a high
      functional significance of nuclear HBx, consistent with the concept that
      transactivation may involve interactions with nuclear proteins.

PMID- 11468726
TI  - Administration of a human monoclonal antibody (TUVIRUMAB) to chronic hepatitis B
      patients pre-treated with lamivudine: monitoring of serum TUVIRUMAB in immune
      complexes.
AB  - A human monoclonal anti-hepatitis B antibody preparation (TUVIRUMAB) was
      administered 6 times over a 2-week period in a dose-escalating scheme to chronic
      hepatitis B patients pre-treated with lamivudine. The capacity of the TUVIRUMAB
      antibody to "neutralize" hepatitis B surface antigen in the circulation was
      investigated by means of experimental enzyme-immunoassays. Monoclonal antibody
      conjugates enabled the detection of HBsAg, TUVIRUMAB, and HBsAg/TUVIRUMAB
      complexes. The results showed that (1) TUVIRUMAB was able partially to
      "neutralize" in vitro and in vivo, (2) HBsAg/TUVIRUMAB complexes can be traced by
      assays that capture the complex at either its HBsAg or its TUVIRUMAB component,
      (3) the final concentration of TUVIRUMAB at the end of therapy varied greatly but
      seemed to be related to HBsAg production at the start of therapy, (4) for at
      least 14 days after discontinuation of therapy, a minimal HBsAg level could be
      maintained in the presence of a declining TUVIRUMAB titer in patients with less
      than 3 microg/ml HBsAg before the start of therapy, (5) three months after
      therapy, all HBsAg levels had returned to pre-treatment levels and TUVIRUMAB had
      disappeared.

PMID- 11468727
TI  - Predominance of genotype A HBV in an HBV-HIV-1 dually positive population
      compared with an HIV-1-negative counterpart in Japan.
AB  - Hepatitis B virus (HBV) has seven genotypes, A to G. Previous studies have shown
      that genotype C is the most prevalent strain in chronic HBV carriers in East
      Asia. This study was undertaken to investigate the epidemiology of HBV genotypes
      among Japanese patients who are coinfected with human immunodeficiency virus type
      1 (HIV-1). The sequences of the complete hepatitis B surface antifen (HBsAg)
      genes were obtained from 18 coinfected Japanese patients. Among the 18 patients,
      12 of 13 men who had sex with men (MSM) had genotype A (92%), whereas only one of
      five heterosexual or hemophiliac patients had genotype A. The predominance of
      genotype A HBV in MSM showed a striking contrast to the current genotype
      prevalence in the Japanese population. Owing to the recent decrease in the rate
      of vertical transmission in Japan, the role of sexual behavior in the
      transmission of HBV cannot be overestimated. Thus, the relative proportion of
      genotype A may gradually increase in Japan.

PMID- 11468728
TI  - Hepatitis B virus DNA in serum of healthy black African adults positive for
      hepatitis B surface antibody alone: possible association with recombination
      between genotypes A and D.
AB  - In some patients with chronic liver disease induced by hepatitis B virus, viral
      DNA is known to persist in low concentration in serum after seroconversion to
      hepatitis B surface antibody-positivity. This phenomenon has, however, not been
      documented in asymptomatic black African carriers of hepatitis B virus. Using
      nested amplification by the polymerase chain reaction, we detected low
      concentrations of hepatitis B virus DNA in the serum of 6 of 23 (26%) healthy
      black African adults with normal liver function and with hepatitis B virus
      surface antibody as the only serological marker of the virus. This finding offers
      one explanation for the earlier observation of integrated hepatitis B virus DNA
      in hepatocellular carcinomas in black Africans whose serum was positive for
      surface antibody alone. A number of genetic changes were found in the six
      isolates that might be responsible for evasion of the immune response and
      persistence of the virus. Isolated mutations were detected in the "a" determinant
      of the surface gene and in the encapsidation signal. In all five isolates
      sequenced in the core promoter, mutations were present in the upstream regulatory
      region. Recombination between genotypes A and D was present in three of the
      isolates, including both of those in which the entire genome was sequenced. This
      change in genotype also overlapped the amino end of the polymerase domain and may
      result in sufficiently low levels of replication to allow viral persistence.
      Topoisomerase 1 specific trinucleotides were concentrated in the vicinity of the
      recombination breakpoints.

PMID- 11468729
TI  - Clearance kinetics of hepatitis C virus under different antiviral therapies.
AB  - Interferon alpha (IFN) has been the standard treatment for hepatitis C virus
      (HCV) infection. Using the kinetic curves of viral clearance, this study compared
      three treatment regimes based on IFN alone or in combination with Amantadine or
      Ribavirin to determine the mechanisms of action and the most suitable way to use
      these drugs. The early clearance kinetics of HCV were studied in 22 patients with
      chronic hepatitis C under different antiviral treatments: IFN 3 MU daily (7 pts);
      IFN 3 MU daily plus Amantadine 200 mg (7 pts); and IFN 3 MU daily plus Ribavirin
      1-1.2 gr (8 pts), for 6 months. HCV-RNA was assessed qualitatively and
      quantitatively on serial samples. The HCV-RNA decay curves suggested a different
      behaviour of viral clearance induced by the three treatments. While no
      significant differences were present in the first 6 hours, between 6 to 12 hours
      Ribavirin induced a rapid decline in the viral load. Amantadine seemed to
      accelerate it in the third phase (12 to 30 hours) and to provoke a more
      pronounced viral decline when compared to IFN alone (P < 0.05) or to IFN plus
      Ribavirin (P < 0.025) (baseline to 30 hours). Thus, while IFN remains the
      principal antiviral drug, Amantadine upholds the viral decline. Ribavirin,
      although synergistic with IFN, does not seem to improve the IFN effect during the
      earliest phase of treatment but probably supports the effects of IFN later on. A
      new dynamic approach to HCV treatment can therefore be developed.

PMID- 11468730
TI  - Multicenter randomized study comparing initial daily induction with high dose
      lymphoblastoid interferon vs. standard interferon treatment for chronic hepatitis
      C.
AB  - One hundred fifty-five chronic hepatitis C patients were assigned at random to
      receive natural lymphoblastoid interferon (IFN)alpha-n1, s.c., for 13 months in
      one of three treatment regimens: initial daily induction with 10 million units
      (MU) followed (group 1, n = 50) or not (group 2, n = 52) by 1 month of rest and
      then three times weekly 10 MU (2 months), 5 MU (2 months), and 3 MU (8 months);
      group 3 (n = 53) received tiw 5 MU (2 months) followed by 3 MU (11 months). By
      intention-to-treat analysis, ALT normalization at completion of treatment was
      greater in patients who received continuous IFNalpha-n1 therapy with initial
      daily induction (group 2: 24/52, 46%) compared with those given intermittent
      therapy with initial daily induction (group 1: 17/50, 34%) and those who received
      standard IFNalpha-n1 therapy (group 3, 18/53, 34%; P not significant). The
      sustained ALT response was 26%, 27% and 21% and the sustained virological
      response was 20%, 27%, and 19%, in groups 1, 2, and 3, respectively. A trend was
      observed towards a higher biochemical and virological end-of-treatment response
      in patients given induction therapy (17%) compared with standard therapy (6%, P =
      0.053). Sustained biochemical and virological responses were 20%, 27%, and 17% in
      groups 1, 2, and 3, respectively. Platelet and leukocyte counts decreased
      following daily high-dose treatment and remained low until therapy cessation (P <
      0.001). The data suggest that daily s.c. induction with 10 MU IFNalpha-n1
      followed by intermittent or continuous maintenance therapy for 1 year does not
      improve the results achieved with the standard 1-year IFNalpha course in the
      treatment of chronic hepatitis C patients.

PMID- 11468731
TI  - Molecular characterization of hepatitis C virus genotype 2a from the entire
      sequences of four isolates.
AB  - Genotype 2a hepatitis C virus (HCV) has different characteristics from genotype
      1b, such as responsiveness to interferon therapy. Such type-specific
      characteristics appear to be due to differences in the HCV genome sequence. The
      complete sequences of genotype 2a HCV genome isolated from four patients with
      chronic hepatitis C were determined, and nucleotide and deduced amino acid
      sequences were compared within genotype 2a, as well as between genotype 2a and
      1b. Whereas the amino acid sequence similarity of the core region was highest
      within genotype 1b, the NS3 and NS4B regions of exhibited greater similarity than
      the core region in genotype 2a. The serine protease and helicase motifs in the
      NS3 region were well conserved in genotype 2a to the same degree as in genotype
      1b. However, the putative secondary structure of 2a isolates was significantly
      different from that of the 1b isolates. Analysis of amino acid similarity between
      genotypes 2a and 1b revealed the lowest degree of similarity in the E1 region,
      followed by the NS2 and NS5A region. Sequences of genotype 2a in the interferon
      sensitivity determining region (ISDR) located in the NS5A region had a deletion
      of four amino acids compared with that of genotype 1b. When the ISDR of the
      genotype 2a was aligned for maximal similarity, it exhibited similarity of only
      52.5-55.0% when compared with that of HCV-J, which belongs to genotype 1b. These
      findings for the entire sequences of genotype 2a isolates will contribute to
      virological studies of HCV.

PMID- 11468732
TI  - Evolution of the E2 region of hepatitis C virus in an infant infected by mother
      to-infant transmission.
AB  - To demonstrate vertical transmission of hepatitis C virus from an HCV infected
      woman and to assess the evolution of HCV quasispecies in the infant, the variable
      E2 region was analyzed in one mother-infant pair at birth and in serial samples
      from the infected baby. Sequence analysis of the E2 region obtained by means of
      direct sequencing of PCR products of mother-infant pair at birth, showed that the
      sequence of the dominant strain in the infant was related closely but not
      identical to that of her mother. The HCV population in mother-infant pair at
      birth and in serial samples of the infant was analyzed by polymerase-chain
      reaction-mediated Single Strand Conformational Polymorphism analysis (SSCP),
      which can distinguish DNA fragments of the same size as different electrophoretic
      migration of single stranded DNA. Single Strand Polymorphism analysis revealed
      that the infant was infected with two mutant genomes whereas the mother had a
      unique variant. The prevalent strain detected in the baby was not dominant in the
      mother at delivery and the pattern of quasispecies in the infant at birth was not
      the same as her mother, suggesting that the infant acquired the infection in
      utero. Changes in the dominant strain and evolution of the pattern of
      quasispecies in the infant from the 10th month of age were possibly due to the
      immune selection of escape mutants.

PMID- 11468733
TI  - Enterovirus sequences resembling coxsackievirus A2 detected in stool and spleen
      from a girl with fatal myocarditis.
AB  - A 10-year-old girl who died suddenly was found at post mortem to have
      myocarditis. Virus could not be cultured from post-mortem stool, spleen or heart
      but enterovirus RNA was detected in stool and spleen by PCR, and the stool caused
      flaccid paralysis in newborn suckling mice. A 654 base pair (bp) sequence from
      the capsid-coding region of the viral genome was amplified from an affected mouse
      and sequenced. Using this sequence, strain-specific nested primers were designed
      and used to amplify viral sequences directly from stool and spleen. These
      sequences were identical to each other and to that obtained from the infected
      mouse, and most closely resembled Coxsackievirus A2, an uncommon serotype rarely
      associated with myocarditis. Testing spleen tissue may be useful in etiological
      investigation of suspected viral myocarditis. PCR proved more sensitive than
      suckling mouse inoculation in detecting this Coxsackievirus, but a combination of
      both methods was required for genotypic characterization.

PMID- 11468734
TI  - Suppression of proinflammatory cytokines and induction of IL-10 in human
      monocytes after coxsackievirus B3 infection.
AB  - Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is
      accompanied by an intense mononuclear leukocyte infiltration. Because myocardial
      tissue damage may either result from viral infections or from a dysregulated
      immune response, the susceptibility of human monocytes and macrophages to CVB3
      was examined in this study with regard to virus replication, virus persistence,
      and release of cytokines. Monocytes were infected by CVB3 as shown by the
      intracellular appearance of plus- and minus-strand viral RNA, which was also
      capable of persisting for more than 10 days. Fresh monocytes were not permissive
      for full virus replication whereas monocyte-derived macrophages yielded a low
      amount of new viruses, which led to cell death. Although CVB3 infection induced
      the mRNA for the proinflammatory cytokines tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-1, and IL-6, only little cytokine production occurred.
      When infected monocytes were stimulated in addition by lipopolysaccharides (LPS),
      cytokine production was partially suppressed. In striking contrast, IL-10
      expression was strongly and persistently induced by CVB3 on the mRNA and the
      protein level. These data show a dysregulated cytokine response in CVB3-exposed
      human monocytes and macrophages, which is characterized by a suppression of
      proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid
      CVB3, causing chronic myocardiopathy.

PMID- 11468735
TI  - Complete replication of human cytomegalovirus in explants of first trimester
      human placenta.
AB  - Tissue integrity and viability of first trimester placenta explants were obtained
      in culture for 3 weeks. Explants were infected with human cytomegalovirus (HCMV),
      several cycles of HCMV replication were obtained and the progression of the
      infection was observed within a tissue that maintains its normal cellular
      organization. In agreement with recent clinical data, 3 weeks were necessary for
      the virus to colonize the placenta fully. Complete HCMV replication was observed
      in trophoblasts, followed by subsequent transmission of the infection to the
      stromal fibroblasts and fetal endothelial capillary cells. Viral DNA replication
      was monitored and the production of infectious viral progeny documented.

PMID- 11468736
TI  - Dynamics of Epstein-Barr virus DNA levels in serum during EBV-associated disease.
AB  - A real-time polymerase chain reaction assay for quantitation of Epstein-Barr
      virus (EBV) DNA in serum was developed. This assay detected EBV DNA in 24 (89%)
      of 27 sera from patients with infectious mononucleosis, but only in 9 (18%) of 51
      sera from EBV carriers (P < 0.001) and in none of the sera from 32 EBV
      seronegative individuals. EBV DNA levels were higher in sera from infectious
      mononucleosis (median 8,000, range 1833-150,069 copies/ml) than from carriers
      (median < 2, range < 2-2980; P < 0.001). In sera of 36 children with infectious
      mononucleosis followed prospectively, EBV DNA levels correlated inversely with
      the duration of symptoms. Among 18 children with tumors including Hodgkin's
      disease (n = 7), non-Hodgkin's lymphoma (n = 6), Burkitt's lymphoma (n = 1),
      lymphoproliferative disorder (n = 4), and osteosarcoma (n = 1), EBV DNA was
      detected in serum from those 9 (100%) expressing EBV in the tumor (Hodgkin's
      disease, 3; non-Hodgkin's lymphoma, 2; lymphoproliferative disorder, 4), the
      levels peaking at diagnosis and correlating with disease activity. Quantitation
      of EBV DNA in serum may offer a simple means of monitoring patients at risk of
      EBV-associated lymphoproliferation.

PMID- 11468737
TI  - Epstein-Barr virus involvement is mainly restricted to lymphoepithelial type of
      gastric carcinoma among various epithelial neoplasms.
AB  - To demonstrate the association of Epstein-Barr virus (EBV) with primary
      epithelial neoplasms in the south part of Kyushu, Japan, 761 carcinomas
      consisting of 75 lung, 61 breast, 107 esophagus, 102 colon, 58 pancreas, 45
      thyroid, and 313 gastric cancers were examined by EBER-1 in situ hybridization.
      EBER-1 was detected in 23 cases (7.3%) out of 313 gastric carcinomas, while none
      of the other carcinomas was positive for EBER-1. Twenty-eight (9.4%) out of 313
      gastric carcinomas were differentiated poorly to moderately carcinomas with
      prominent lymphoid cell infiltration, similar to so-called lymphoepithelioma-like
      carcinoma, and 19 cases (67.9%) were positive for EBER-1. Although two (2.6%) and
      11(10.3%) out of 75 lung and 107 esophagus carcinomas were so-called
      lymphoepithelioma-like carcinomas, respectively, but EBER-1 was not detected in
      other epithelial neoplasms that originated from the lung, esophagus, breast,
      colon, pancreas, and thyroid in the south of Kyushu, Japan. As a result, EBV was
      associated with only some gastric carcinomas but not with other epithelial
      neoplasms originating from the lung, esophagus, breast, colon, pancreas, and
      thyroid in southern Japan.

PMID- 11468738
TI  - Coupled particle light scattering: a new technique for serodiagnosis of Epstein
      Barr virus infection.
AB  - The Coupled Particle Light Scattering technique was evaluated for serological
      diagnosis of Epstein-Barr Virus (EBV) infection. Two hundred ninety-six patient
      sera selected from several clinical categories (acute infection, non-primary
      infection, interfering non-EBV infection, non-infected) were tested for IgM and
      IgG antibodies (anti-VCA, anti-EBNA and anti-EA). Determination of EBV IgG with
      Copalis multiplex was accurate when compared with Enzygnost Anti-EBV/IgG ELISA.
      Although the sensitivity of Copalis IgM for acute infections was 100% a positive
      IgM result did not always indicate an acute infection. Strong reactivity to IgG
      EA (ratio 3, 1) and IgG VCA (ratio 13, 3) correlated with persistent infection or
      reactivation. The CopalisI has many advantages over the existing methods, such as
      the possibility to measure three semi-quantitative IgG responses to three
      different EBV antigens simultaneously.

PMID- 11468739
TI  - Prevalence and age distribution of human herpesvirus-8 specific antibodies in
      Hungarian blood donors.
AB  - Sera of blood donors were investigated by a peptide ELISA and indirect
      immunofluorescence assay to assess the prevalence of HHV-8 infection in the
      Hungarian population. A 14 amino acid long synthetic oligopeptide from the
      carboxyterminus of orf65/small virus capsid antigen was used as antigen in the
      ELISA. ELISA results were confirmed by recombinant orf65 antigen Western blot.
      Antibodies to the latent nuclear antigen were detected by the immunofluorescence
      assay. Nine of 12 sera obtained from patients with classical Kaposi sarcoma were
      reactive by ELISA whereas all were positive by immunofluorescence. Four of 482
      (0.83%) healthy blood donors had anti-orf65 peptide antibodies and 17/1089
      (1.56%) had antibodies to the latent nuclear antigen. In a group of children ages
      1-14 years, antibodies to the latent nuclear antigen (0/29) were not detected.
      The prevalence of antibodies to the latent nuclear antigen showed a moderate but
      significant increase in correlation with senescence. In the Kaposi sarcoma
      patients, the titre of antibodies to the latent nuclear antigen was significantly
      higher than in the healthy seropositive donors. The overall HHV-8 seroprevalence
      by the two assays was 2.28% (11/482) in the Hungarian blood donor group.

PMID- 11468740
TI  - Screening for possible failure of herpes simplex virus PCR in cerebrospinal fluid
      for the diagnosis of herpes simplex encephalitis.
AB  - The objectives of this study were to evaluate the reliability of herpes simplex
      virus (HSV) PCR testing in cerebrospinal fluid (CSF) for the detection of herpes
      simplex encephalitis. This was done by examining retrospectively the clinical
      follow-up of a large group of patients tested routinely by HSV-PCR. In addition,
      an attempt was made to assess the incidence of herpes simplex encephalitis in a
      central European population. CSF samples from 1,427 patients from all Vienna
      hospitals were submitted for HSV-PCR testing during a period of 4 years and 8
      months. Herpes simplex encephalitis was detected by PCR in 12 cases and by
      serological methods in one additional patient. Retrospective analysis of the
      course of disease, which was possible in 799 PCR-negative patients, led to the
      identification of three additional cases in which herpes simplex encephalitis
      appears to have occurred despite negative PCR results. Failure of the PCR in
      these patients is most likely due to the time of obtaining CSF during the course
      of disease. A high specificity of the assay was demonstrated by the lack of false
      positive results in any of the 708 cases in which other causes for the
      neurological symptoms had been identified in the follow-up. The incidence of
      herpes simplex encephalitis in the population of Vienna was between 1
      case/469,000-577,000 individuals/year. The highest annual incidence was detected
      in the age group between 3 months and 3 years, which, however, could not be
      confirmed statistically.

PMID- 11468741
TI  - Type-specific identification of human adenovirus 3, 7, and 21 by a multiplex PCR
      assay.
AB  - Human adenovirus (Ad) serotypes 3, 7, and 21 of DNA cluster B:1 are often
      associated with severe respiratory illness, particularly in infants and young
      children and, in addition to Ad4, are among the most important causes of acute
      respiratory disease syndrome in new military recruits. To address the inherent
      problems associated with classic typing methods, we developed a multiplex PCR
      assay for the rapid, specific identification of Ad3, Ad7, and Ad21 field
      isolates. To design type-specific primers for our assay, we sequenced the Ad21
      hexon gene and compared this sequence with previously published sequences of Ad3,
      Ad7, and Ad16. The overall nucleotide (nt) and amino acid (aa) identities between
      Ad21 and Ad3, Ad7, and Ad16 were similar (ranges 78.3-80.8% nt; 84.1-86.2% aa),
      with significantly greater variability in the regions of the hexon that encode
      surface loops 1 and 2. Type-specific primers designed to the hypervariable
      regions correctly identified Ad3, Ad7, and Ad21 prototype strains and 53
      previously typed Ad field isolates. No cross-reactions with other Ad serotypes
      were identified. Our multiplex PCR assay for type-specific identification of Ad3,
      Ad7, and Ad21 isolates will provide a rapid and convenient tool for the
      epidemiologic investigation of Ad-associated respiratory illness.

PMID- 11468742
TI  - A case of human orf in an immunocompromised patient treated successfully with
      cidofovir cream.
AB  - Immunocompromised patients may have severe forms of infections. Since there is an
      increasing number of patients maintained under immunosuppressive therapy, we will
      be confronted with increasing frequency with these infectious problems. Effective
      treatments will be of great value. The case is described of a renal transplant
      with a giant orf lesion, which continued growing instead of regressing
      spontaneously as is observed usually. The treatment options in such patients are
      limited. It was decided to treat the patient with the antiviral drug cidofovir
      (HPMPC, Vistide. Topical cidofovir treatment resulted in complete regression of
      the lesion. This case is discussed in the context of the known literature on orf
      (ecthyma contagiosum).

PMID- 11468743
TI  - Detection of multiple human papillomavirus types in the lower genital tract
      correlates with cervical dysplasia.
AB  - Some human papillomavirus (HPV) types, such as HPV 16, are clearly associated
      with cervical dysplasia; however, the role played by other HPV types occasionally
      found in dysplasia is less certain. In addition, most methods used to detect HPV
      in clinical specimens cannot easily distinguish among more than two or three HPV
      types in a single specimen. Therefore, the significance of infection with
      multiple HPV types is not known. To address this question, we analyzed
      cervicovaginal lavage specimens from three cohorts of women for HPV DNA using a
      PCR/reverse blot assay system that permits the detection and partial quantitation
      of 26 genital HPV types. As expected, 94.1% of women who had dysplasia (n = 34)
      and 71.4% of women who had atypical squamous cells of uncertain significance
      (ASCUS) (n = 21) on cytology had HPV DNA detected compared to 54.5% of age
      matched women with normal cytology. HPV 16 DNA was detected in 35% of dysplasia
      patients compared to 9% of cytologic normals (P = 0.0044). Dysplasia patients had
      a mean of 3.29 (range 0-10) different HPV types detected compared to 1.04 (range
      0-7) HPV types among those with normal cytology (P < 0.0001). These data support
      a possible role for multiple HPV types in the development or progression of
      cervical dysplasia.

PMID- 11468744
TI  - Analysis of the relationship between immunogenicity and immunity for viral
      subunit vaccines.
AB  - The prevention of viral infection by vaccination relies on stimulating an
      appropriate immune response in order to reduce the probability with which a virus
      can establish an infection. Post-vaccination antibody responses have therefore
      been associated with reducing the probability with which an individual can be
      infected (i.e., the vaccine's "impact"). Quantifying this relationship is
      essential in evaluating new vaccines, especially since comparisons between
      vaccines, and vaccine licensure, may be dependent on antibody responses alone. In
      this paper two principal questions are identified which need to be addressed in
      the evaluation of subunit vaccines: i) how do specific antibody levels relate to
      complete protection from infection or disease and ii) how do antigenic subunits
      interact in developing protection when combined together in a single vaccine. The
      aim is to identify explicitly certain assumptions that are frequently made
      implicitly in the discussion of vaccine action. First, antibody levels are
      related to levels of protection through a novel statistical analysis of incidence
      data from a published hepatitis B vaccine trial. The antibody response observed
      after influenza A virus infection is discussed in relation to the selection of
      neutralisation escape variants. Finally, by way of example, a theoretical
      situation is examined and three simple models of subunit vaccine action are
      constructed in order to describe how antibody levels may be related to population
      level phenomena such as the elimination of an infection by mass vaccination.

PMID- 11468745
TI  - Nucleotide sequence analysis and development of consensus primers of RT-PCR for
      detection of Norwalk-like viruses prevailing in Japan.
AB  - A total of 177 different nucleotide sequences of the RNA polymerase region of
      Norwalk-like viruses (NLVs) genomes, collected via a nation-wide survey project
      in Japan between 1989 and 1998, were examined by reverse transcription-polymerase
      chain reaction (RT-PCR) employing various primer pairs. The nucleotide sequences
      of different strains showed great diversity, with a range of 57 to 100%
      identities among strains. The strains could be classified into five clusters:
      Norwalk (NV), Snow Mountain agent/Bristol virus (SMA/BV), Toronto virus/Mexico
      virus (TV/MX), and Japan specific cluster 1 and 2 (JP-1 and JP-2). Within each
      cluster there is greater than 85% identity of amino acid sequence (more than 75%
      identity of nucleotide sequences), based on sequence homology analysis. We
      believe that two of the five clusters, JP-1and JP-2, define new specific clusters
      found in Japan according to phylogenetic and pair-wise comparison studies. An RT
      PCR procedure was designed using new consensus primer pairs, P1/P2, P1/P3, and
      Y1/Y2 based on multiple alignment of collected nucleotide sequences, that are
      expected to detect nearly all NLVs prevailing in Japan. The usefulness of the
      primers was tested by ten different laboratories in Japan using a panel of ten
      fecal samples containing different virus strains. The identification of these
      primer pairs will facilitate routine diagnosis of NLV infection by RT-PCR and
      offers the potential for their direct detection in food and environmental
      samples.

PMID- 11468746
TI  - Detection of adeno-associated virus DNA in female genital samples by PCR-ELISA.
AB  - Adeno-associated viruses (AAV) are human parvoviruses that require helper
      function for their replication. Several studies have demonstrated that AAV DNA
      sequences can be found in the female genital tract but the incidence of infection
      seems very variable. A PCR-ELISA method detecting AAV DNA was developed for
      combining the specificity and the sensitivity of conventional PCR with an
      objective interpretation of the results. In the PCR-ELISA, a defined number of
      cells from cervical specimens were digested and amplified with concomitant
      digoxigenin labeling. Digoxigenin-labeled amplified products hybridized to a
      specific biotinylated probe were captured in streptavidin-coated microtiter wells
      by a biotin-streptavidin binding and were visualized by colorimetric
      immunoenzymatic reaction. PCR-ELISA was carried out in 110 cervical cytological
      specimens of women with or without the concomitant detectable presence of
      papillomavirus (HPV) DNA and the results were compared with those obtained by
      conventional PCR followed by dot blot hybridization. When compared to
      conventional PCR considered as reference standard, PCR-ELISA was found to be 98%
      sensitive and 96% specific. Out of the total 110 samples examined, 52.7% were
      positive for AAV DNA by both techniques, demonstrating a high prevalence of AAV
      infection in the uterine cervix. When analyzing samples with or without the
      presence of HPV DNA, 63.2 % of the samples were positive for HPV DNA and 41.5% of
      the samples were negative for HPV proved positive for AAV DNA by both PCR-ELISA
      and conventional PCR. Hence, PCR-ELISA, which can be completed in 1 day, proved
      to be a reliable method for an objective detection of AAV DNA in clinical
      samples. The present study showed a frequent infection of the cervical epithelium
      with AAV both in the presence and absence of HPV infection.

PMID- 11468747
TI  - Sequence analysis of genes encoding structural and nonstructural proteins of a
      human group B rotavirus detected in Calcutta, India.
AB  - Nucleotide sequences of RNA segments encoding structural proteins(VP4, VP6, and
      VP7) and nonstructural proteins(NSP1 and NSP3) of a human group B rotavirus CAL
      1, which was detected in Calcutta, India, were determined and their relatedness
      with cognate genes of other group B rotaviruses was analyzed. The CAL-1 genes
      showed generally high sequence identities (more than 90%) to those of human group
      B rotavirus, adult diarrheal rotavirus (ADRV) in China, while identities with
      bovine, murine, and ovine viruses were considerably lower (58-73%). Among RNA
      segments analyzed, sequence identity of the VP6 gene was relatively high compared
      with other gene segments. In the CAL-1 VP7 sequence, many characteristics were
      shared by ADRV, but not by other animal group B rotaviruses. In contrast, VP4 and
      NSP3 of CAL-1 were single amino acid and 23 amino acids longer than those of ADRV
      strain, respectively, due to differences of a few nucleotides. These findings
      suggested that human group B rotaviruses CAL-1 and ADRV might have originated
      from a common ancestral virus distinct from animal group B rotaviruses reported
      so far, while some notable sequence differences indicated the distinct nature of
      these viruses.

PMID- 11468748
TI  - Full-length genomic analysis of hepatitis B virus isolates in a patient
      progressing from hepatitis to hepatocellular carcinoma.
AB  - In hepatitis B virus (HBV)-endemic countries, the majority of hepatocellular
      carcinoma (HCC) arises in HBV carriers. High frequency of mutations at
      nucleotides 1762(A-->T) and 1764(G-->A) in the core promoter region have been
      described in HCC. Due to the differences in genetic backgrounds, environmental
      risk factors and random cellular insertion sites, it is difficult to analyze the
      possible roles of HBV variants detected in different HCC patients. In a follow-up
      cohort study, an HBsAg-positive asymptomatic carrier was diagnosed HCC within 4
      years. Eleven full-length HBV isolates, three from the first serum sample
      obtained 4 years pre-HCC, and eight from serum sample, peri-tumor and tumor
      tissue post-HCC of this individual were sequenced and used to transfect HepG2
      cells. When sequences were compared between pre- and post-HCC isolates, no single
      mutation common to all post-HCC isolates that differed from pre-HCC isolates was
      found. Among all 11 isolates, there were 20 predicted amino acid substitutions
      shared by two or more post-HCC isolates. These were located in the S(5), X(4),
      core(4), polymerase(4), pre-S1(2) and pre-S2(1) proteins. Possible roles of amino
      acid substitutions and enhanced replication efficiency in cells transfected by
      post-HCC isolates are discussed.

PMID- 11468749
TI  - Female dominance in captive gray mouse lemurs (Microcebus murinus).
AB  - Female dominance or female feeding priority seem to be characteristic for many
      lemur species, but are rare traits in other primates and mammals in general. The
      nocturnal lemur species, however, are underrepresented in the quantitative
      studies on social dominance. The aim of this study is to investigate the pattern
      of intersexual dominance relationships in the gray mouse lemur (Microcebus
      murinus), a species that is generally thought to possess a number of ancestral
      lemur traits. The context, distribution, and outcome of intersexual conflicts are
      analyzed in four captive groups of gray mouse lemurs. Intersexual conflicts
      occurred in the study groups in different behavioral contexts and were mostly
      spatial interactions (chasing/fleeing, approach/avoidance). The majority of
      conflicts were decided, and were in all but one case won by females. This is the
      first evidence suggesting unconditional female dominance in a cheirogaleid
      primate. The existence of female dominance in most families of the Lemuriformes
      suggests it is an ancient trait that evolved in their common ancestor.

PMID- 11468750
TI  - Changes in yearling rhesus monkeys' relationships with their mothers after
      sibling birth.
AB  - The birth of a new sibling is believed to signify an abrupt and important
      transition in a young primate's relationship with its mother-one that is of
      potential importance from at least three theoretical perspectives: attachment
      theory, parent-offspring conflict theory, and dynamic assessment models. This
      study examines changes in relationships between free-ranging yearling rhesus
      monkeys (Macaca mulatta) and their mothers concomitant with the birth of the
      mother's next infant, and tests predictions derived from each theoretical
      perspective. We observed 31 yearling rhesus on Cayo Santiago, Puerto Rico, 3
      months before and 3 months after their siblings' births, using focal animal
      sampling methods. Changes in measures related to mother-yearling interaction and
      yearling distress were examined using repeated-measures analysis of variance.
      After sibling birth, mothers and yearlings abruptly reduced amounts of time in
      contact and increased amounts of time at a distance and out of sight of one
      another. Mothers and yearlings played approximately equal roles in bringing about
      decreases in proximity, and yearlings took the primary roles in bringing about
      decreases in contact. Rates of maternal aggression toward yearlings increased
      immediately and markedly after birth, possibly providing yearlings with early
      cues regarding subsequent decreased levels of maternal care. There were no marked
      increases in overt signs of yearling distress (e.g., vocalizations or tantrums)
      following the births. We conclude that yearlings generally acquiesced to reduced
      levels of care, responding behaviorally with increased independence and maturity.
      In this sense, our study provides preliminary support for dynamic assessment
      models over attachment theory and parent-offspring conflict theory models.

PMID- 11468751
TI  - Sources of variability in numbers of live births in wild golden lion tamarins
      (Leontopithecus rosalia).
AB  - We examined the effects of several variables on the number of live births in
      multiparous females in a wild population of golden lion tamarins (Leontopithecus
      rosalia). Independent variables included the number of infants born to a female
      the previous breeding season, the number of infants weaned the previous breeding
      season, the female's age and body mass, the number of adult males and helpers in
      the group, and the inbreeding coefficient of the offspring. We also tested the
      hypothesis that trapping and chemical immobilization during pregnancy affected
      the number of live births. Female body mass was the only statistically
      significant predictor of the number of live-born infants in the current season
      when both first and second peaks were included. Characteristics that predicted
      higher numbers of infants in the first peak of a season were the number of
      infants born the previous season and the body mass of the female. The greater the
      number of infants born the previous season, the greater the number of infants
      born in the first peak of the current season. Factors positively correlated with
      the number of live births in the second peak within a season included the number
      of infants born the previous season, as well as the number of available helpers.
      Due to sample size constraints, the analysis of litters in the second peak did
      not include body mass of the female as a variable. Inbreeding and handling did
      not affect the number of live births. We found no evidence that current
      reproduction negatively impacts future reproduction in this species. We also
      found no evidence for an age-related reduction in fertility.

PMID- 11468752
TI  - Toward developing a genome-wide microsatellite marker set for linkage analysis in
      the rhesus macaque (Macaca mulatta): identification of 76 polymorphic markers.
AB  - Linkage analysis can be problematic in humans because of the lack of large,
      multigenerational pedigrees and the difficulties in obtaining phenotypic data on
      all family members. In contrast, large, captive colonies of rhesus macaque are a
      potentially valuable resource for linkage studies because detailed phenotypic and
      genealogical data are kept, inbreeding is avoided, and DNA samples can usually be
      obtained. Microsatellite marker sets for genome-wide screening are available in a
      number of species, but not for the rhesus macaque. We tested primers to 400 human
      microsatellite markers from a genome-wide mapping set using DNA from nine
      unrelated female rhesus macaques. We found that 76 (19%) of the primers amplified
      a polymorphic product using the standard protocols for human DNA. The average
      heterozygosity of the markers in humans was 0.80, compared to 0.65 in the rhesus
      macaques. This study provides preliminary data, which could be used toward the
      development of a linkage mapping set in this species. There would be a need,
      however, to confirm the Mendelian inheritance of the markers.

PMID- 11468753
TI  - Are bonobos (Pan paniscus) really more bipedal than chimpanzees (Pan
      troglodytes)?
AB  - Of the living apes, the chimpanzee (Pan troglodytes) and bonobo (Pan paniscus)
      are often presented as possible models for the evolution of hominid bipedalism.
      Bipedality in matched pairs of captive bonobos and chimpanzees was analyzed to
      test hypotheses for the evolution of bipedalism, derived from a direct
      referential model. There was no overall species difference in rates of bipedal
      positional behavior, either postural or locomotory. The hominoid species differed
      in the function or use of bipedality, with bonobos showing more bipedality for
      carrying and vigilance, and chimpanzees showing more bipedality for display.

PMID- 11468761
TI  - Meta-analysis of continuous outcome data from individual patients.
AB  - Meta-analyses using individual patient data are becoming increasingly common and
      have several advantages over meta-analyses of summary statistics. We explore the
      use of multilevel or hierarchical models for the meta-analysis of continuous
      individual patient outcome data from clinical trials. A general framework is
      developed which encompasses traditional meta-analysis, as well as meta-regression
      and the inclusion of patient-level covariates for investigation of heterogeneity.
      Unexplained variation in treatment differences between trials is considered as
      random. We focus on models with fixed trial effects, although an extension to a
      random effect for trial is described. The methods are illustrated on an example
      in Alzheimer's disease in a classical framework using SAS PROC MIXED and MLwiN,
      and in a Bayesian framework using BUGS. Relative merits of the three software
      packages for such meta-analyses are discussed, as are the assessment of model
      assumptions and extensions to incorporate more than two treatments.

PMID- 11468762
TI  - Meta-analysis of ordinal outcomes using individual patient data.
AB  - Meta-analyses are being undertaken in an increasing diversity of diseases and
      conditions, some of which involve outcomes measured on an ordered categorical
      scale. We consider methodology for undertaking a meta-analysis on individual
      patient data for an ordinal response. The approach is based on the proportional
      odds model, in which the treatment effect is represented by the log-odds ratio. A
      general framework is proposed for fixed and random effect models. Tests of the
      validity of the various assumptions made in the meta-analysis models, such as a
      global test of the assumption of proportional odds between treatments, are
      presented. The combination of studies with different definitions or numbers of
      response categories is discussed. The methods are illustrated on two data sets,
      in a classical framework using SAS and MLn and in a Bayesian framework using
      BUGS. The relative merits of the three software packages for such meta-analyses
      are discussed.

PMID- 11468763
TI  - Cumulative logit models for ordinal data: a case study involving allergic
      rhinitis severity scores.
AB  - Ordered categorical data arise in numerous settings, a common example being pain
      scores in analgesic trials. The modelling of such data is intrinsically more
      difficult than the modelling of continuous data due to the constraints on the
      underlying probabilities and the reduced amount of information that discrete
      outcomes contain. In this paper we discuss the class of cumulative logit models,
      which provide a natural framework for ordinal data analysis. We show how viewing
      the categorical outcome as the discretization of an underlying continuous
      response allows a natural interpretation of model parameters. We also show how
      covariates are incorporated into the model and how various types of correlation
      among repeated measures on the same individual may be accounted for. The models
      are illustrated using longitudinal allergy data consisting of sneezing scores
      measured on a four-point scale. Our approach throughout is Bayesian and we
      present a range of simple diagnostics to aid model building.

PMID- 11468764
TI  - Administrative and artificial censoring in censored regression models.
AB  - Administrative censoring, in which potential censoring times are known even for
      subjects who fail, is common in clinical and epidemiologic studies. Nonetheless,
      most statistical methods for failure-time data do not use the information
      contained in these potential censoring times. Robins has proposed two approaches
      for using this information to estimate parameters in an accelerated failure-time
      model; the methods generally require the analyst to treat as censored some
      subjects whose failure time is observed. This paper provides a rationale for this
      "artificial censoring", discusses some of its consequences, and illustrates some
      of these points with data from a randomized trial of breast cancer screening.

PMID- 11468765
TI  - Order-restricted dose-related trend tests.
AB  - Methods of isotonic regression are proposed to increase the power of common trend
      tests in situations where a monotonicity constraint is imposed upon the dose
      response function. Isotonic versions of Cochran-Armitage type trend tests for
      binary response data are developed, and the bootstrap method is used in finding
      the empirical distributions of the test statistics and their critical values. The
      isotonic likelihood ratio test with a survival adjustment is also proposed. This
      survival adjustment can be applied to the likelihood ratio test for either the
      order-restricted or unrestricted parameter cases. To achieve the isotonic
      modifications, an amalgamation algorithm is applied when the observed dose
      response is non-monotonic. A Monte Carlo simulation study comparing these trend
      tests shows the advantages of the isotonic modifications and survival adjustment.
      By applying the proposed methods to data from a toxicology and carcinogenesis
      study conducted as part of the National Toxicology Program, the effect of CI
      Pigment Red 23 is investigated.

PMID- 11468766
TI  - Diffusion and prediction of Leishmaniasis in a large metropolitan area in Brazil
      with a Bayesian space-time model.
AB  - We present results from an analysis of human visceral Leishmaniasis cases based
      on public health records of Belo Horizonte, Brazil, from 1994 to 1997. The main
      emphasis in this study is on the development of a spatial statistical model to
      map and project the rates of visceral Leishmaniasis in Belo Horizonte. The model
      allows for space-time interaction and it is based on a hierarchical Bayesian
      approach. We assume that the underlying rates evolve in time according to a
      polynomial trend specific to each small area in the region. The parameters of
      these polynomials receive a spatial distribution in the form of an autonormal
      distribution. While the raw rates are extremely noisy and inadequate to support
      decisions, the resulting smoothed rates estimates are considerably less affected
      by small area issues and provide very clear directions to implement public health
      actions.

PMID- 11468767
TI  - Using the overdispersed exponential family to estimate the distribution of usual
      daily intakes of people aged between 18 and 28 in Taiwan.
AB  - Assessment of usual dietary intake of a population is essential to understand the
      nutrition status of the population. Methods like 24-hour dietary recall and food
      records are commonly used for this task. However, within-individual variation
      exists in the food record data. Methods considering measurement errors have been
      used to evaluate the association between nutrient intakes and diseases. Few have
      been devoted to estimating the distribution of usual daily intakes. This paper
      proposes applying the formulation of the overdispersed exponential family to
      estimate the distribution of usual nutrient intake and applies the adjustments
      developed by Liu to reduce the variance of the distribution. The proposed method
      has the advantages of working on the original scale of data and implementation
      convenience. The adjustment of the variance is carried out by dividing the
      variance into within-individual variance and among-individual variance. The
      adjusted variance, then, is used to estimate the distribution of the usual daily
      intake. Sampling weights are considered in all the steps, except the estimation
      of the ratio of within to among variance. The data for this study are from the
      Nutritional and Health Survey in Taiwan conducted between 1993 and 1996 (NAHSIT,
      1993-1996). An independent external set of data for people aged between 18 and 28
      years (49 males and 20 females) is used to estimate the ratio of within to among
      individual variance. Due to the availability of data in estimating the ratio of
      within to among individual variance, 430 males and 422 females in the NAHSIT
      sample are used to estimate the distribution of usual daily intakes for people
      aged between 18 and 28 in Taiwan. The distribution also allows us to estimate the
      proportion of people who do not meet the recommended daily nutrient allowance
      (RDNA). The results show that the intakes of calcium and vitamin E of this group
      of people fall far below RDNA.

PMID- 11468768
TI  - Using structural equation models to evaluate the magnitude of measurement error
      in blood pressure.
AB  - This article aims to compare alternative methods for estimating the quality of
      blood pressure measurements. Traditional within-subject variance estimates in
      mixed analysis of variance models are compared to multiple-group multitrait
      multimethod models, which are a particular case of mean-and-covariance-structure
      confirmatory factor analysis models. Confirmatory factor analysis models belong
      to the family of structural equation models and were specifically developed to
      analyse psychosociological traits measured by tests or surveys, but they have
      also proved suitable for evaluating the quality of blood pressure measurements.
      Confirmatory factor analysis models are less restrictive and provide more
      detailed information than traditional approaches, enable researchers to compute
      weighted averages of individual measures with optimal measurement quality, make
      it easier to correct the biasing effects of measurement error on the results of
      substantive studies, and make the use of equivalent replicated measures
      unnecessary under certain conditions.

PMID- 11468769
TI  - Imputation of missing values in the case of a multiple item instrument measuring
      alcohol consumption.
AB  - Missing values in survey instruments are a common problem for survey researchers.
      It is aggravated in the case of instruments used to measure alcohol consumption:
      they usually consist of item batteries from which summary measures, such as grams
      of pure alcohol per day, are constructed, and a missing value (for example,
      quantity or frequency) in regard to a single item for only one of several
      beverages results in a missing summary measure across all of the beverages,
      though the values for the remaining items are known. The present paper examines
      different approaches to imputation of missing values, feasible with standard
      statistical software packages. Hot-deck imputation is shown to have certain
      advantages, but even single-value imputation (for example, median imputation)
      results in values that are comparable to those of the other three imputation
      methods.

PMID- 11468770
TI  - Spermatid manchette: plugging proteins to zero into the sperm tail.
AB  - Spermiogenesis pursues three major objectives: (1) The safeguard of the male
      genome within the confines of a compact nucleus. (2) The accumulation of enzymes
      in the acrosome of be released at fertilization. (3) The development of a sperm
      propelling tail consisting of an axoneme surrounded by a scaffold of keratin
      containing outer dense fibers and a fibrous sheath. Recent experimental data
      indicate that three keratins-Sak57, 0df1 and 0df2-and other proteins (the 26S
      proteasome and the 0df1-binding protein Spag4) are temporarily stored in the
      manchette before being sorted to the developing sperm tail. These findings
      support a general model for the manchette as an ephemeral structure timely
      developed and strategically positioned to provide a transient storage to both
      structural and signaling proteins. Some of the proteins are later sorted to the
      developing tail; others may participate in the reciprocal nuclear-cytoplasmic
      signaling pathways as the gene activity of the male genome gradually becomes
      silent. Mol. Reprod. Dev. 59: 347-349, 2001.

PMID- 11468771
TI  - Characterization of a novel gene, sperm-tail-associated protein (Stap), in mouse
      post-meiotic testicular germ cells.
AB  - During mammalian spermatogenesis, many specific molecules show the dynamics of
      expression and elimination, corresponding with the morphological differentiation
      of germ cells. We have isolated a novel cDNA designated F77 from mouse testis by
      cDNA subtractive hybridization between normal and sterile mice, using the C57BL/6
      congenic strain for the hybrid sterilityhyphen;3 lpar;Hsthyphen;3rpar; allele
      from Mus spretus. The full-length F77 mRNA was 3.4 kb and showed significant
      nonmatching with entries in the databases. F77 was mapped at a proximal position
      between D8Mit212 and D8Mit138 on mouse chromosome 8, in which no corresponding
      genes related to its nucleotide sequence were found. F77 mRNA was not detected in
      any other organs except the testis of adult fertile mice. F77 protein was only
      seen in normal adult testis and epididymis. In contrast to normal C57BL/6 mice,
      F77 mRNA and protein were not seen in germ cell-deficient Kit(W)/Kit(Wv) mice. By
      in situ hybridization, F77 mRNA was detected mainly at round spermatids in the
      sexually mature testis, and immunohistochemical analysis revealed that F77
      protein was located at the tail of elongated spermatids. We are proposing the
      name, sperm-tail-associated protein (Stap), for the gene encoding F77 cDNA. Mol.
      Reprod. Dev. 59: 350-358, 2001.

PMID- 11468772
TI  - Cloning of brain aromatase gene and expression of brain and ovarian aromatase
      genes during sexual differentiation in genetic male and female Nile tilapia
      Oreochromis niloticus.
AB  - A brain aromatase gene was identified from the Nile tilapia Oreochromis
      niloticus. The cDNA sequence of this gene differed from that of the ovarian
      aromatase gene previously reported from this species. Tissue specific expression
      for both brain and ovarian aromatase genes was examined in the tissues of adult
      tilapia. Brain aromatase mRNA was expressed in the brain, kidney, eye, ovary, and
      testis, but not in the liver and spleen. Ovarian aromatase mRNA was expressed in
      the brain, spleen, ovary, and testis but not in the eye, kidney, and liver.
      Differential aromatase gene expression between the sexes was investigated in all
      male (XY) and all-female (XX) groups of tilapia fry from fertilisation throughout
      the sexual differentiation period. Semi-quantitative RT-PCR analysis revealed
      that the initiation of expression of both aromatase genes lay between 3 and 4 dpf
      (days post fertilisation) in both sexes. The level of brain aromatase mRNA
      gradually increased throughout the period studied with little difference between
      the sexes. This contrasted with marked sexual dimorphism of ovarian aromatase
      mRNA expression. In females, the expression level was maintained or increased
      gradually throughout ontogeny, while the level in males was dramatically down
      regulated between 15 and 27 dpf. Subsequently, the level of ovarian aromatase
      mRNA expression fluctuated slightly in both sexes, with the expression in females
      always being higher than in males. These findings clearly suggest that ovarian
      aromatase plays a decisive role in sexual differentiation in this species and
      that this is achieved by down-regulation of the expression of this gene in males.
      Mol. Reprod. Dev. 59: 359-370, 2001.

PMID- 11468773
TI  - Remodeling of donor nuclei, DNA-synthesis, and ploidy of bovine cumulus cell
      nuclear transfer embryos: effect of activation protocol.
AB  - The purpose of this study was to investigate the effects of two activation
      protocols on nuclear remodeling, DNA synthesis during the first cell cycle,
      chromosome segregation after first mitosis and development to blastocyst of
      embryos produced by somatic nuclear transfer. Pronuclear formation was
      significantly higher when activation lasted 5 hr compared to 3 hr for both
      ethanol-cycloheximide and ionomycin-bohemine treatment. However, the presence of
      a single nucleus was significantly higher in embryos activated for 3 hr in
      bohemine. Initiation of DNA synthesis was delayed in ethanol-cycloheximide group,
      however, after 12 hr labeling 100% of embryos synthesized DNA in both groups.
      Embryos activated with ethanol-cycloheximide developed to blastocysts at a
      significantly higher rate than those activated with ionomycin-bohemine. Analysis
      of 2-cell embryos with DNA probes for chromosome 6, 7, and 15 by fluorescence in
      situ hybridization showed that at least 50% of NT embryos were of normal ploidy
      independent of the activation stimulus. The results presented in this study show
      differences between the protocols compared on the nuclear events during the first
      cell cycle and on the development to blastocyst. Mol. Reprod. Dev. 59: 371-379,
      2001.

PMID- 11468774
TI  - Production of germ-line chimeras in rainbow trout by blastomere transplantation.
AB  - We describe a technique for producing germ-line chimeric rainbow trout,
      Oncorhynchus mykiss, by microinjection of the isolated blastomeres. FITC-labeled
      donor cells and non-labeled recipient embryos at various developmental stages
      between the early blastula and early gastrula stages were used for cell
      transplantation. The chimera formation rate and the degree of donor cell
      distribution in recipient embryos were evaluated at both the late gastrula stage
      (5 days post fertilization (dpf)) and the 40-somite stage (10 dpf). Among the six
      combinations of developmental stages of donor and recipient embryos, the
      combination of midblastula (2.5 dpf) donor cells and early blastula (1.5 dpf)
      recipient embryos gave the highest chimera formation rate and the best
      distribution pattern of donor cells. Using this combination, chimeric rainbow
      trout were produced with donor blastomeres from dominant orange-colored mutant
      embryos and wild-type recipient embryos. Of the 238 chimeric embryos produced, 28
      (12%) hatched normally and 14 of the 28 fry (50%) had donor-derived orange body
      color. To test for germ-line transmission of donor cells, gametes obtained from
      the matured chimeras were fertilized with gametes from wild-type fish. Of the 19
      matured chimeras, 6 (32%) yielded donor-derived orange-colored progeny, in
      addition to wild-type siblings. The contribution rates of donor cells in the germ
      line ranged from 0.3 to 14%. This technique for producing germ-line chimeras
      should be a powerful tool for cell-mediated gene transfer in rainbow trout.
      Especially, if body color mutants are used for either donor cells or the host
      embryos, it will be possible to easily concentrate F1 transgenic embryos derived
      from transplanted donor cells by body color screening. Mol. Reprod. Dev. 59: 380
      389, 2001.

PMID- 11468775
TI  - Uterine-embryonic interaction in pig: activin, follistatin, and activin receptor
      II in uterus and embryo during early gestation.
AB  - The mRNA expression patterns of activin beta(A) and follistatin in the uterus and
      embryo, the mRNA expression of the activin receptor II in the embryo, and the
      localization in the uterus of the immunoreactive activin beta(A) and the receptor
      II proteins in the uterus were examined at gestation days 7-12 after ovulation in
      pig. Activin was located predominantly at the mesometrial side of the uterus
      during all stages of pregnancy studied. Follistatin mRNA was absent in the uterus
      during these stages, suggesting that activin of uterine origin is not inhibited
      by intra-uterine follistatin. The receptor was localized throughout the glandular
      and luminal epithelium of the uterus. In the embryo, activin was expressed
      predominantly in the epiblast before unfolding, but after unfolding of the
      epiblast activin expression shifted to the trophoblast. The expression pattern of
      follistatin mRNA was contrarily to that of activin, i.e., before unfolding
      predominantly in the trophoblast (days 8-9), and shifted to the epiblast at day
      10. During streak stages, follistatin was detected in the node and primitive
      streak. Activin receptor II mRNA was first detected at day 8 in the embryoblast.
      At day 11, it was expressed in trophoblast cells near the epiblast, and in the
      first ingressing mesoderm cells. During the streak stages, it was expressed
      predominantly in the trophoblast. The presence of activin and its receptor in
      uterine epithelium and early embryonic tissues indicate that both embryonic and
      uterine activin are involved in intra-uterine processes, such as attachment and
      early embryonic development. Mol. Reprod. Dev. 59: 390-399, 2001.

PMID- 11468776
TI  - Establishment and characterization of an immortalized human oviductal cell line.
AB  - Human oviductal cells stimulate embryo development in vitro partly by the
      production of embryotrophic glycoproteins. The identity of these glycoproteins is
      not yet known mainly because oviductal samples are limited and that the cultured
      parental oviductal cells cannot produce sufficient amount of embryotrophic
      factors for characterization. In this study, human oviductal epithelial cells
      (OE) were immortalized by HPV 16 E6/E7 open reading frame (ORF) by retroviral
      expression. The characteristics of this immortalized cell line (OE-E6/E7) were
      compared to the parental OE. HPV 16 E6/E7 DNA was found only in OE-E6/E7 but not
      in OE. Human oviduct-specific glycoprotein, estrogen receptors, and cytokeratin
      were found in both cell types. Both OE and OE-E6/E7 possessed telomerase
      activities but the former had much lower activity. OE-E6/E7 also produced
      glycoproteins with chromatographic behavior similar to the embryotrophic
      glycoproteins derived from OE. These results showed that OE-E6/E7 retained a
      number of characteristics of OE. The development of preimplantation mouse embryo
      was significantly better after coculture with OE-E6/E7 when compared to medium
      alone culture in term of blastulation rates (52% vs. 32%) and blastocyst diameter
      (113.0 +/- 2.07 microm vs. 83.9 +/- 5.23 microm). This immortalized cell line can
      be used as a continuous and stable in vitro system for the study of the oviductal
      embryotrophic activity. Mol. Reprod. Dev. 59: 400-409, 2001.

PMID- 11468777
TI  - Testicular protein Spag5 has similarity to mitotic spindle protein Deepest and
      binds outer dense fiber protein Odf1.
AB  - Outer dense fibers (ODF) and the fibrous sheath (FS) are major cytoskeletal
      structures in the mammalian sperm tail. The molecular mechanisms underlying their
      morphogenesis along the axoneme or their function are poorly understood.
      Recently, we reported the cloning and characterization of Odf2, a major ODF
      protein, and Spag4, an axoneme-binding protein, by virtue of their strong
      interaction with Odf1, the 27 kDa major ODF protein. We proposed a crucial role
      for leucine zippers in molecular interactions during sperm tail morphogenesis.
      Here we report the cloning and characterization of a novel gene, Spag5, which
      encodes a 200 kDa testicular protein that interacts strongly with Odf1. Spag5 is
      transcribed and translated in pachytene spermatocytes and spermatids. It bears
      73% similarity with the mitotic spindle protein Deepest of unknown function. We
      identified two putative leucine zippers in the C-terminal part of the Spag5
      protein, the downstream one of which is involved in interaction with Odf1.
      Interestingly, these motifs are present in Deepest. These results highlight the
      importance of the leucine zipper in sperm tail protein interactions. Mol. Reprod.
      Dev. 59: 410-416, 2001.

PMID- 11468778
TI  - Cigarette smoking and aneuploidy in human sperm.
AB  - Cigarette smoke contains chemicals which are capable of inducing aneuploidy in
      experimental systems. These chemicals have been shown to reach the male
      reproductive system, increasing oxidative DNA damage in human sperm and lowering
      semen quality. We have examined the association between smoking and aneuploid
      sperm by studying 31 Chinese men with similar demographic characteristics and
      lifestyle factors except for cigarette smoking. None of the men drank alcohol.
      These men were divided into three groups: nonsmokers (10 men), light smokers (<
      20 cigarettes/day, 11 men), and heavy smokers (> or = 20 cigarettes/day, 10 men).
      There were no significant differences in semen parameters or in age across
      groups. Two multi-color fluorescence in situ hybridizations (FISH) were
      performed: two-color FISH for chromosomes 13 and 21, and three-color FISH for the
      sex chromosomes using chromosome 1 as an internal autosomal control for diploidy
      and lack of hybridization. The mean hybridization efficiency was 99.78%. The
      frequency of disomy 13 was significantly higher in light and heavy smokers than
      in non-smokers, while no significant differences in the frequency of disomy 21, X
      or Y were observed across groups. Significant inter-donor heterogeneity in every
      category of disomic sperm examined was found in both light and heavy smokers,
      while in nonsmokers only XY disomy showed significant inter-donor differences.
      Thus, we conclude that cigarette smoking may increase the risk of aneuploidy only
      for certain chromosomes and that men may have different susceptibilities to
      aneuploidy in germ cells induced by cigarette smoking. Mol. Reprod. Dev. 59: 417
      421, 2001.

PMID- 11468779
TI  - Storage in the yolk platelets of low MW DNA produced by the regressing follicle
      cells.
AB  - The present work was carried out to clarify the nature and origin of the yolk DNA
      present in vitellogenic oocytes of the lizard Podarcis sicula. Morphological and
      biochemical evidences indicate that it has an intrafollicular origin, from the
      apoptotic bodies resulting from follicle cells regression at the end of
      previtellogenesis. This conclusion is reinforced by the observation that the
      oocyte membrane, in in vitro experiments, is unpermeable to exogenous DNA.
      Biochemical evidences reveal that the yolk DNA has a low (200bp) molecular weight
      and this suggests that it is produced by the endonucleases typically involved in
      apoptotic DNA laddering. Indeed, immunocytochemical analyses demonstrate that
      follicle cells contain significant amounts of DNAse I. In immunoblots, carried
      out during different periods of the ovarian cycle, the enzyme shows a MW of about
      33, 66 or 100 kDa thus indicating that its activity in the follicle of Podarcis
      is modulated by dimerization and/or binding to regulatory factors. Mol. Reprod.
      Dev. 59: 422-430, 2001.

PMID- 11468780
TI  - Identification and characterization of P31m, a novel sperm protein in Cynomolgus
      monkey (Macaca fascicularis).
AB  - We have previously described a hamster sperm glycoprotein, P26h, which is
      implicated in the cascade of events occurring during the interaction between
      mature spermatozoa and the oocyte's zona pellucida. The P26h is acquired on the
      acrosomal cap of the spermatozoon during its maturation arising within the
      epididymis. Lately, using a polyclonal antiserum raised against P26h, a 34 kDa
      protein, P34H, has been identified on the acrosomal cap of the human
      spermatozoon. The cloning and sequencing of the cDNA encoding P34H has revealed a
      65% similarity between the P34H and P26h amino acid sequences. Considering that
      P26h shows total immunocontraceptive properties in the hamster, it is of relevant
      importance to have an animal model phylogenetically closer to the human. Using
      the Cynomolgus monkey, we searched for a protein autologous to the human P34H. A
      31 kDa protein, the P31m, localized on the acrosomal cap of the monkey
      spermatozoon has been identified by a Western blot analysis and by
      immunohistochemical techniques using an anti-hamster P26h antiserum. Northern
      blot analysis showed increasing high levels of the P31m mRNA through the
      epididymis and at lower levels in the testis. In situ hybridization showed the
      presence of the P31m mRNA in the principal cells of the epididymis. The cloning
      and sequencing of the cDNA encoding the P31m showed a high homology of 97%
      identity between the P31m and P34H nucleotidic sequences. This study clearly
      demonstrates that the monkey P31m is the homologous protein of the hamster P26h
      and of the human P34H. Mol. Reprod. Dev. 59: 431-441, 2001.

PMID- 11468781
TI  - Nuclear fragmentation characterises paraspermiogenesis in Tubifex tubifex
      (Annelida, Oligochaeta).
AB  - It is known that tubificine oligochaetes produce two types of spermatozoa:
      eusperm, fertilizing sperm with regular haploid DNA content; and parasperm, with
      a much lower DNA content, protecting and carrying the eusperm. Whereas mature
      spermatozoa and spermatids of the two lines are easily recognized by their
      morphology and DNA content, little is known about the first steps of
      differentiation of the two lines. This subject is addressed here in two ways: we
      have measured DNA content by a new method based on confocal laser microscopy and
      found that the total DNA content of parasperm cysts is extremely variable and
      equal or lower than total DNA content of eusperm cysts. Then we focused on the
      spermatocytes, and we found that the cells which will form paraspermatids undergo
      a peculiar kind of nuclear fragmentation which differ greatly from a regular cell
      division. During fragmentation DNA is distributed unevenly among the spermatids
      and this gives rise to a great and variable number of parasperm with variable DNA
      content. Immunocytochemical assays revealed that a proper meiotic spindle is
      never formed during fragmentation and that actin may play an important role in
      the chromatin division. Electron micrographs showed that the centrioles undergo a
      phenomenon of mass reproduction similar to that found in ciliated epithelia which
      supplies each of the numerous paraspermatids of its basal body. Mol. Reprod. Dev.
      59: 442-450, 2001.

PMID- 11468782
TI  - Production of reactive oxygen species by spermatozoa undergoing cooling,
      freezing, and thawing.
AB  - In the present study, we provide evidence for the production of reactive oxygen
      species (ROS) during cryopreservation of bovine spermatozoa. Cooling and thawing
      of spermatozoa cause an increase in the generation of superoxide radicals.
      Although nitric oxide production remains unaltered during sperm cooling from 22-4
      degrees C, a sudden burst of nitric oxide radicals is observed during thawing.
      Increase in lipid peroxidation levels have been observed in frozen/thawed
      spermatozoa and appears to be associated with a reduction in sperm membrane
      fluidity as detected by spin labeling studies. The data presented provide strong
      evidence that oxygen free radicals are produced during freezing and thawing of
      bovine spermatozoa and suggest that these reactive oxygen species may be a cause
      for the decrease in sperm function following cryopreservation. Mol. Reprod. Dev.
      59: 451-458, 2001.

PMID- 11468783
TI  - Nuclear ultrastructure in bovine oocytes after inhibition of meiosis by chemical
      and biological inhibitors.
AB  - Various components of the ovarian follicle as well as different chemicals can
      suppress the resumption of meiosis in cumulus-oocyte complexes (COCs). In this
      study the nuclear ultrastructure of bovine COCs was assessed after 8 h of meiotic
      inhibition with 50 microM roscovitine (ROSC), 50 microM butyrolactone (BL-I), 2
      mM 6-DMAP, 2 microM cycloheximide (CX), or a theca cell monolayer (TC). COCs were
      recovered according to standard in vitro methods, cultured in a simple and
      defined medium, and processed for transmission electron microscopy. Control COCs
      were processed before onset of culture and multiple oocytes were evaluated for
      each treatment. In all groups, the oocyte nucleus presented a dense fibrillar
      nucleolus consisting of a fibrillar sphere with a fibrillar center. In TC and 6
      DMAP inhibited COCs condensed chromatin adhered to the nucleolus while in all
      other groups the perinuclear chromatin was separated from the nucleolus. In ROSC
      inhibited COCs, the nuclear envelope presented only slight small amplitude
      undulation. The BL-I-inhibited COCs presented an intermediate level of low
      amplitude undulation of the NE. In CX, 6-DMAP, and TC inhibited COCs the nuclear
      envelope presented extensively low amplitude undulations. In ROSC inhibited COCs,
      electron-dense granules formed ring-shaped structures. In some of the BL-I
      inhibited COCs multiple stellate crystal-like structures were found, and in these
      COCs the nuclear envelope and the perinuclear cisternae appeared less distinct
      than in the other BL-I inhibited COCs. In 6-DMAP inhibited COCs interchromatin
      like granule clusters were present. In conclusion, the oocyte nuclei in all COCs
      presented a dense fibrillar nucleolus resembling that in control COCs. However,
      variations were observed in 1) the nuclear envelope morphology; 2) the chromatin
      location in relation to the nucleolus; and 3) the presence of different
      populations of intranuclear granules. Although all treatments inhibited oocyte
      nucleus breakdown, the mechanisms underlying these effects are different and
      require further characterization. Mol. Reprod. Dev. 59: 459-467, 2001.

PMID- 11468784
TI  - Minireview: Parthenogenesis in mammals.

PMID- 11468785
TI  - Dyspepsia in Spain.

PMID- 11468786
TI  - Epidemiology of dyspepsia in a random mediterranean population. Prevalence of
      Helicobacter pylori infection.
AB  - AIM: The prevalence of dyspepsia in the community is poorly known, because most
      studies have used samples that were not representative of the general population.
      This study was intended to determine the prevalence of dyspepsia in a random
      sample of the general population, and its epidemiologic and sociodemographic
      characteristics. METHODS: In this descriptive study we used a questionnaire
      administered during a personal interview to survey a random sample of 264
      subjects in a Mediterranean population. RESULTS: The prevalence of dyspepsia was
      24%; we found no relation between prevalence and demographic characteristics,
      smoking and drinking, or type of dyspepsia. Forty subjects with dyspepsia were
      examined and the specific diagnosis was found in 18 (45%) of them. The subgroup
      with reflux-like dyspepsia was the largest (60%), although there was considerable
      overlap between subgroups with reflux-like, ulcer-like and dysmotility-like
      dyspepsia. Anti-Helicobacter pylori antibodies (IgG) were found in 52% of the
      subjects, but bacterial infection was not related with dyspepsia. CONCLUSIONS: Up
      to one-fourth of the general population in the city where the subjects reside may
      have dyspepsia. This disorder was associated with irritable bowel syndrome in
      half of the cases, but was not associated with H. pylori infection.

PMID- 11468787
TI  - Resistance of Helicobacter pylori to antimicrobial treatment in a Seville
      hospital catchment area.
AB  - AIM: To determine the sensitivity to metronidazol, clarithromycin, amoxicillin
      and tetracycline of strains of Helicobacter pylori isolated in a prospective
      series of patients referred to a university hospital in Seville for endoscopic
      examination. METHODS: During the period from March 1998 to July 1999 we studied
      117 patients with ulcer. The diagnosis of bacterial infection was based on the
      rapid urease test, histological study, Gram staining or culture of gastric biopsy
      material (from the antrum and corpus) obtained during gastroscopy. Susceptibility
      studies were done with the diffusion method using E-test strips. RESULTS:
      Helicobacter pylori infection was found in 64 patients. A total of 58 strains
      were grown, 40 of which were from patients who had received no previous treatment
      to eradicate the infection (69%), and 18 of which were from patients who had
      failed one or more eradication therapies (31%). In the first group, metronidazol
      resistance was found in 42%, clarithromycin resistance in 13%, and resistance to
      both in 10% of the patients. In the second group these rates were 39%, 44% and
      17% respectively, and one strain was found which was also resistant to
      tetracyclines (2%). No strains resistant to amoxicillin were found. CONCLUSIONS:
      We found high rates of resistance, especially to clarithromycin, and especially
      in patients who had received previous eradication therapy. Empirical treatments
      should use effective antimicrobials and avoid regimens based on a single
      antibiotic. Culture of gastric biopsy samples provides information on the
      resistance to antimicrobials in a given setting, and this information can be used
      to develop the most rational treatment for the infection.

PMID- 11468788
TI  - Doppler ultrasonography in the assessment of renal hemodynamics in patients with
      chronic liver disease.
AB  - AIM: To assess renal hemodynamics by Doppler analysis of resistive index (RI) in
      small intrarenal arteries in patients with chronic liver diseases at different
      stages, and to analyze renal RI in patients with cirrhosis as a function of the
      absence or presence of ascites and the response to diuretic therapy. METHODS:
      Prospective cross-sectional study of 24 patients with chronic hepatitis, 39 with
      compensated cirrhosis, and 34 with ascites. The last group was divided into two
      subgroups: 1) responders to sodium restriction and a low dose of diuretics, and
      2) patients with refractory ascites or those requiring high-dose therapy.
      RESULTS: Renal RI was increased in patients with cirrhosis and ascites (0.68 +/-
      0.06) in comparison with patients with compensated cirrhosis (0.63 +/- 0.03, p <
      0.01). Renal RI in the latter group was higher than in patients without cirrhosis
      (0.61 +/- 0.04, p < 0.05). Renal RI in patients with ascites was lower in
      subgroup 1 than in subgroup 2 (0.65 +/- 0.05 vs 0.72 +/- 0.06, p < 0.01).
      CONCLUSIONS: Renal RI increases as liver disease progresses. Patients with
      cirrhosis and ascites and increased RI require high-dose treatment or do not
      respond. Further studies are needed to demonstrate the predictive value of renal
      RI in assessing the effectiveness of diuretic therapy.

PMID- 11468789
TI  - Epidemiological characteristics and socioeconomic importance of irritable bowel
      syndrome.
AB  - In summary, in light of the flood of figures, statistics, and epidemiological
      evidence, the socioeconomic importance of IBS cannot be questioned. The
      development of new, effective treatments that would control the symptoms is a
      huge challenge for researchers and the pharmaceutical industry. Drugs able to
      relieve the symptoms of IBS would provide great relief to a large number of
      patients, and would save the health system considerable effort and resources.

PMID- 11468790
TI  - [Escherichia coli O157:H7 and hemolytic uremic syndrome in an HIV positive
      patient].

PMID- 11468791
TI  - [Rifampicin as a cause of acute pancreatitis].

PMID- 11468792
TI  - [Upper gastrointestinal hemorrhage of unusual etiology].

PMID- 11468793
TI  - [Abdominal distension].

PMID- 11468794
TI  - [Necrotizing enterocolitis caused by Aspergillus in immunodepressed patient].

PMID- 11468795
TI  - Gardens of paradise.
AB  - Two hundred and fifty years ago, the Swedish naturalist Carolus Linnaeus (1707
      1778) published his Philosophia botanica. This textbook in botanical science was
      widely read well into the 19th century. Today it is remembered mainly for two
      things: the introduction of binomial nomenclature and the formulation of a fixist
      and creationist species concept. While the former achievement is seen as a
      practical tool, still applicable for purposes of identification and information
      retrieval, the latter is usually deemed to have been one of the main obstacles to
      scientific progress in biology. That both achievements were not independent of
      each other, but interlocked theoretically and grounded in a specific scientific
      practice still thriving today--the collection of plant specimens in botanical
      gardens--is usually overlooked. The following article tries to uncover these
      connections and to demonstrate the significance that Linnaeus' achievements had
      for modern biology.

PMID- 11468796
TI  - British cell theory on the eve of genetics.
AB  - Many historians have assumed that the advent of the chromosome theory of heredity
      and the theory of the gene settled the old debate over preformation versus
      epigenesis in favour of preformation. An analysis of the views of leading British
      cytologists between 1900 and 1920 indicates that the story is more complex.
      Cytologists could accept seemingly preformationist tenets about the hereditary
      factors and yet maintain an overall epigenetic view of organism development by
      assuming that genes interact dynamically with the cytoplasm and that the cell is
      influenced by its environment throughout growth and development.

PMID- 11468797
TI  - Discrepancies in the values of standard atmospheric pressure: the riddle
      resolved.
AB  - Over half a century ago, when I took Beginning Physics at university, I was
      bothered by the anomaly that normal air pressure (which is arbitrary anyhow) was
      taken to be 1.013250 bar instead of a sensible 1.000000 bar. My professor could
      not explain why, nor could any of the many other scientists whom I have asked
      since then. Now in retirement, I have made a laborious search in utterly
      uncharted territory and discovered the answer.

PMID- 11468798
TI  - Alfred Russel Wallace's North American tour: transatlantic evolutionism.
AB  - Evolutionary theory aroused vigorous debate in the late-19th century, regarding
      both its scientific status and its sociocultural implications. Alfred Russel
      Wallace's lecture tour of North America, during 1886-1887, affords a striking
      insight into his particular interpretation of evolution and reveals the depth of
      his conviction that science was inseparable from ethical and political realities.
      Wallace's views on matters scientific and cultural were as controversial and
      significant in North America as they were in Great Britain and Europe.

PMID- 11468799
TI  - Retrospective biological dosimetry of absorbed radiation.
AB  - Frequencies of chromosomal translocations in human peripheral blood lymphocytes
      irradiated in vitro by 200 kV X rays have been estimated by the fluorescence in
      situ hybridisation (FISH) technique. Probes specific for whole chromosomes 1, 3
      and 4 were labelled with, biotin 16 dUTP + digoxigenin 11 dUTP; biotin 16 dUTP
      and digoxigenin 11 dUTP respectively, to achieve three colour FISH to distinguish
      exchanges involving individual chromosomes. The translocation frequencies for
      individual chromosomes suggested a relationship between the response and the
      genomic content of the chromosomes studied. Dose-response curves derived from
      translocations involving all the three painted chromosomes (22.3% of the genome)
      showed a linear-quadratic response with alpha and beta coefficients of 0.027 +/-
      0.009 Gy-1 and 0.033 +/- 0.004 Gy-2, corresponding coefficients for the response
      curves extrapolated to the entire genome are 0.072 +/- 0.026 Gy-1 and 0.075 +/-
      0.011 Gy-2 respectively. Dose-response curves for the induction of dicentrics
      involving painted chromosomes also showed a similar response, but the dicentric
      frequencies were consistently lower than the translocation frequencies for all
      the doses studied. Dose fractionation resulted in a small but significant
      reduction in the yield of exchanges, thus suggesting repair of some radiation
      damage during the period between the two fractions. Retrospective biological
      dosimetry was attempted with FISH assay of five radiation workers with
      chronically accumulated doses of approximately 500 mSv received over a period of
      2-3 decades. Among the 2421 metaphases scored in these subjects 28 translocations
      involving the painted chromosomes were detected. The dose estimates based on FISH
      assay ranged from 0.215 +/- 0.116 Gy to 0.635 +/- 0.292 mGy, thus suggesting the
      usefulness of this assay in retrospective biological dosimetry.

PMID- 11468800
TI  - Measured and calculated angular responses of panasonic UD-809 thermoluminescence
      dosemeters to neutrons.
AB  - Multi-element thermoluminescence dosemeters (TLD), such as the Panasonic UD-809,
      are used in personal dosimetry. The Panasonic UD-809 dosemeter consists of one
      gamma sensitive and three neutron sensitive TLD elements with different filter
      materials. In this work, the neutron energy responses (the number of (n,alpha)
      reactions per neutron) of the neutron-sensitive TLD elements of the Panasonic UD
      809 dosemeter were calculated using the MCNP Monte Carlo transport code.
      Experiments were performed in a calibration geometry with an unmoderated 252Cf
      neutron source. These measurements were made with the dosemeter placed on the
      centre front face of a polymethylmethacrylate (PMMA) slab phantom. The phantom
      was rotated in the horizontal plane from -90 to +90 degrees, in 15 degree
      increments. Good agreement between calculated and measured element responses was
      observed. The angular dependency of personal dose equivalent was also calculated
      for parallel beams of 252Cf neutrons and compared to the TLD element angular
      responses.

PMID- 11468801
TI  - Depleted uranium: a problem of perception rather than reality.

PMID- 11468802
TI  - Chest wall thickness measurements and the dosimetric implications for male
      workers in the south Korean uranium industry.
AB  - Using ultrasound techniques, the Human Monitoring Laboratory has measured chest
      wall thicknesses of a group of male workers at the Korea Atomic Energy Research
      Institute. A site-specific biometric equation has been developed for these
      workers, who are somewhat smaller than other workers reported in the literature.
      Chest wall thickness is an important modifier on lung counting efficiency. These
      data have been put into the perspective of the ICRP recommended dose limits for
      occupationally exposed workers: 100 mSv in a 5-year period with a maximum of 50
      mSv in any one year. For measured chest wall thicknesses of 1.9 cm to 4.1 cm and
      a 30 min counting time, the achievable MDAs for natural uranium in the KAERI lung
      counter vary from 6.6 mg to 13.2 mg. These values are close to, or even exceed,
      the predicted amounts of natural uranium that will remain in the lung (absorption
      type M and S) after an intake equal to the Annual Limit on Intake corresponding
      to a committed dose of 20 mSv. This paper shows that the KAERI lung counter
      probably cannot detect an intake of Type S natural uranium in a worker with a
      chest wall thickness equal to the average value (2.7 cm) under routine counting
      conditions.

PMID- 11468803
TI  - Radiation dose estimates in Indian adults in normal and pathological conditions
      due to 99Tcm-labelled radiopharmaceuticals.
AB  - ICRP Publications 53, 62 and 80 give organ dose coefficients and effective doses
      to ICRP Reference Man and Child from established nuclear medicine procedures.
      However, an average Indian adult differs significantly from the ICRP Reference
      Man as regards anatomical, physiological and metabolic characteristics, and is
      also considered to have different tissue weighting factors (called here risk
      factors). The masses of total body and most organs are significantly lower for
      the Indian adult than for his ICRP counterpart (e.g. body mass 52 and 70 kg
      respectively). Similarly, the risk factors are lower by 20-30% for 8 out of the
      13 organs and 30-60% higher for 3 organs. In the present study, available
      anatomical data of Indians and their risk factors have been utilised to estimate
      the radiation doses from administration of commonly used 99Tcm-labelled
      radiopharmaceuticals under normal and certain pathological conditions. The
      following pathological conditions have been considered for
      phosphates/phosphonates--high bone uptake and severely impaired kidney function;
      IDA--parenchymal liver disease, occlusion of cystic duct, and occlusion of bile
      duct; DTPA--abnormal renal function; large colloids--early to intermediate
      diffuse parenchymal liver disease, intermediate to advanced parenchymal liver
      disease; small colloids--early to intermediate parenchymal liver disease,
      intermediate to advanced parenchymal liver disease; and MAG3--abnormal renal
      function, acute unilateral renal blockage. The estimated 'effective doses' to
      Indian adults are 14-21% greater than the ICRP value from administration of the
      same activity of radiopharmaceutical under normal physiological conditions based
      on anatomical considerations alone, because of the smaller organ masses for the
      Indian; for some pathological conditions the effective doses are 11-22% more.
      When tissue risk factors are considered in addition to anatomical considerations,
      the estimated effective doses are still found to be generally somewhat higher for
      the Indian, for both normal and pathological states (but lower than the values
      based on anatomical considerations alone). However, when the radiopharmaceutical
      is administered in quantities proportional to the body mass, the effective doses
      are 11-28% lower for the Indian under both normal and pathological conditions. It
      may be concluded that Indians are at a lower risk of radiation health detriment
      in comparison with the ICRP adult on administration of the various 99Tcm-labelled
      radiopharmaceuticals considered in this study.

PMID- 11468804
TI  - Patient dose, image quality and radiographic techniques for common X ray
      examinations in two Greek hospitals and comparison with European guidelines.
AB  - The radiographic technique factors and the quality of each radiographic image for
      three common examinations (chest PA, pelvis AP and lumbar spine LAT) were
      compared with the European criteria and entrance surface dose (ESD) was measured
      for each radiograph in two Greek hospitals. The measurements were carried out
      using calibrated LiF thermoluminescence dosemeters. The patients were selected so
      that their weight was close to 70 +/- 10 kg and their height to 170 +/- 10 cm.
      Effective dose values were calculated using a PC-based Monte Carlo program. All
      four X ray rooms in the survey achieved mean doses well below the European
      reference doses. However the mean doses in the X ray rooms differed by a factor
      of about 3.

PMID- 11468805
TI  - Study on external exposure doses received by the Cuban population from
      environmental radiation sources.
AB  - The results are described of the study carried out with the aim of assessing
      doses received by the Cuban population due to the external exposure to
      environmental radiation sources. Contributions of cosmic radiation's ionising and
      indirectly ionising components to these doses, as well as the fraction resulting
      from terrestrial radiation, were also assessed as part of this study.
      Measurements made enabled us to estimate representative effective average doses
      received by the Cuban population from external exposure to cosmic and terrestrial
      radiation. Both outdoor and indoor permanency were taken into account for this
      estimate as well as the distribution of the Cuban population by altitude. The
      average representative dose due to cosmic radiation was estimated to be 298 +/-
      17 microSv per year, while the dose received by terrestrial radiation represented
      180 +/- 14 microSv per year, for a total annual dose of 78 +/- 20 microSv. These
      values are within the range of those reported throughout the world by other
      authors.

PMID- 11468806
TI  - Fluence to effective dose conversion coefficients for electrons with energy from
      1 MeV to 100 GeV.
AB  - Fluence to organ dose and effective dose conversion coefficients have been
      calculated for electrons from 1 MeV to 100 GeV using an anthropomorphic phantom
      and the EGS4 code. The conversion coefficients were calculated for six typical
      irradiation geometries taking electromagnetic cascade shower and photonuclear
      reactions into account. The contribution to the absorbed dose due to the
      photonuclear reactions in energies up to 140 MeV was evaluated to be less than
      0.2%. Even at energies above 140 MeV the dose contributions of the photonuclear
      reactions were insignificant.

PMID- 11468807
TI  - Occupational radiation protection dosimetry in Nigeria.
AB  - The general features of occupational radiation protection dosimetry in Nigeria
      within the period 1990-1999 have been summarised. About 640 personnel,
      representing about 25% of the estimated number of radiation workers in Nigeria,
      were monitored by the TL dosimetry technique during the period, with the majority
      being the personnel of the teaching hospitals across the country. Most private
      establishments, especially the X ray diagnostic centres, operate without
      dosimetry coverage or supervision by a regulatory authority. The weighted mean of
      the annual effective dose ranged between 0 and 28.97 mSv with the upper limit of
      collective effective dose being 18.47 man.Sv per year. The individual risk
      estimate due to this is about 1.5 x 10(-3) per year and this was among the
      medical personnel. The value could be more if all radiation workers in the
      country were monitored.

PMID- 11468808
TI  - Urinary excretion and external radiation dose from patients administered thallium
      201 and technetium-99M methoxy isobutyl isonitrile.
AB  - In this study, the dose rates at various distances of 5, 10, 50 and 100 cm from
      70 patients, who were administered diagnostic amounts of 201Tl-chloride and 99Tcm
      MIBI, was measured using an ionisation chamber. The maximum values of external
      dose rates of 201Tl and 99Tcm-MIBI were 11.2 microSv.h-1 +/- 2.3 and 43.1
      microSv.h-1 +/- 11.9 respectively at 5 cm from the patients. Significant exposure
      from patients after injection of 99Tcm-MIBI was limited on the day of
      administration. Departure dose rates of 201Tl fell gradually so by 3 days after
      administration were significant. All excreted urine was also collected from 16
      patients for the 24 days after administration. The urinary excretion rate of
      201Tl was slow; about 2% of the activity within 24 h after injection. The urinary
      excretion of 99Tcm-MIBI was rapid, and a large amount of activity was excreted in
      a few hours after injection; 22% within 20 h after injection.

PMID- 11468809
TI  - Radon progeny in Egyptian underground phosphate mines.
AB  - In addition to the workers in uranium mines, the staff of other underground
      mines, such as workers in underground phosphate mines, can be exposed to 222Rn
      and its progeny. In this study the individual radon progeny concentrations were
      measured in three Egyptian underground phosphate mines to estimate the
      occupational exposure of the workers at those sites. A filter method was used to
      measure individual radon progeny concentrations (218Po, 214Pb and 214Po). The
      reported mean values of radon progeny concentrations exceed the action levels
      which are recommended by ICRP 65 (1993). Based on the measured individual radon
      progeny concentrations (218Po, 214Pb and 214Po) in these mines, the annual
      effective dose for the workers has been calculated using the lung dose model of
      ICRP 66 (1994). According to the obtained results, some countermeasures were
      recommended in this study to minimise these exposure levels.

PMID- 11468810
TI  - Population dose due to building materials in Ibadan, Nigeria.
AB  - The natural radionuclide contents of some concrete building blocks randomly
      sampled in the city of Ibadan have been determined using NaI(Tl) gamma ray
      spectrometry. The radionuclides 226Ra, 232Th and 40K were determined with city
      mean specific activities 47 +/- 21 Bq.kg-1, 52 +/- 21 Bq.kg-1, and 352 +/- 222
      Bq.kg-1, respectively. These activities amount to a radium equivalent of about
      150 Bq.kg-1, which is lower than the recommended maximum value of 370 Bq.kg-1.
      The mean value of the external hazard index was found to be 0.41 which implies
      that the building blocks used in the city of Ibadan are within the acceptable
      level of radioactivity. The mean indoor gamma dose equivalent to individuals due
      to the walls was calculated to be 412 microSv.y-1 and the collective dose
      equivalent 563 man.Sy.y-1.

PMID- 11468811
TI  - Does exposure to residential radon increase the risk of lung cancer?
AB  - In assessing the risks of exposure to ionising radiation, it is important to
      neither overstate nor understate the effects of the hazard. These requirements
      are often difficult to satisfy, especially since much of our knowledge about the
      effects of low levels of radiation is subject to rather large uncertainties. Our
      participants have given their opinions about the risk of lung cancer induction
      resulting from exposure to radon in residences. Each agrees that exposures to
      high concentrations of radon are hazardous. However, as with low level exposures
      to other types of ionising radiation, quantifying relatively small risks is quite
      difficult. The national and international standards setting bodies have
      recommended a fairly conservative approach that may overestimate the 'true'
      magnitude of deleterious effects and their dependence upon exposure, but this is
      to be expected given the uncertainties in the data and the need to avoid
      underestimates. A conservative approach can have both positive and negative
      consequences, and it is also important to neither overstate nor understate these
      consequences.

PMID- 11468812
TI  - Impaired growth in the polychaete Armandia brevis exposed to tributyltin in
      sediment.
AB  - Juveniles of the opheliid polychaete, Armandia brevis, were exposed to sediment
      associated tributyltin (TBT) for 42 days to evaluate toxicity and
      bioaccumulation. Growth in this species was inhibited in a dose-response fashion
      by increasing concentrations of TBT. Even though the biota-sediment accumulation
      factor (BSAF) for TBT declined for the higher sediment concentrations, the total
      butyltins in tissue increased over all sediment concentrations. At the highest
      sediment concentrations, polychaetes bioaccumulated less TBT than expected, which
      was most likely due to reduced uptake and continued metabolism of the parent
      compound. The less than expected BSAF values exhibited by animals at the exposure
      concentrations causing severe effects are an important finding for assessing
      responses in the field. It appears that severe biological effects can occur in
      long-term experiments without the expected high tissue concentrations; an
      observation likely explained by altered toxicokinetics. Analysis of variance
      determined the lowest observed effect concentration for growth to be 191 ng/g
      sediment dry wt. for 21 days of exposure and 101 ng/g sediment dry wt. at day 42,
      indicating that 21 days was insufficient for delineating the steady-state
      toxicity response. When based on regression analysis, the sediment concentration
      causing a 25% inhibition in growth at 42 days exposure was 93 ng/g dry wt. (total
      organic carbon = 0.58%). A dose-response association was also determined for
      polychaete net weight and TBT in tissue. The tissue residue associated with a 25%
      reduction in growth was 2834 ng/g dry wt. at day 42. A comparison of these
      results with previous work indicates that juveniles are approximately three times
      more sensitive than adults to TBT exposure. The sediment concentrations affecting
      growth in this species are commonly found in urban waterways indicating
      potentially severe impacts for this and other sensitive species.

PMID- 11468813
TI  - Species-specific elimination of polychlorinated biphenyls in estuarine animals
      and its impact on residue patterns.
AB  - Elimination kinetics of tetra-, penta- and hexachlorobiphenyls (IUPAC Nos. 44,
      52, 87, 95, 101, 153) were investigated by laboratory experiments in three
      species of different phyla: Nereis diversicolor (Polychaeta), Palaemon
      longirostris (Crustacea) and Platichthys flesus (Pisces). Half-lives were species
      specific and structure-dependent. Palaemon longirostris eliminated all components
      fastest. N. diversicolor was faster than Platichthys flesus except for components
      95 and 153. Contrary to the fish species, the two invertebrates contained
      significant amounts of polar transformation products of No. 52, which had been
      applied as 14C labelled. Therefore, the faster elimination by Palaemon
      longirostris and N. diversicolor was assumed to be generally due to increased
      biotransformation. Elimination was in accordance with polychlorinated biphenyl
      (PCB) residue patterns obtained from field samples of the species. Congeners with
      vicinal H atoms in m,p positions were under-represented in Palaemon longirostris
      and so were congeners with > or = 7 Cl in N. diversicolor, while the PCB residue
      pattern in Platichthys flesus was similar to that of Clophen A60. By comparing
      percentages of the experimental congeners in sigma PCB and their elimination half
      lives in the three species, it was revealed that residue patterns were also
      influenced by species-dependent uptake, e.g. feeding habits. Extractable organic
      matter-based sigma PCB levels increased with trophic levels of the three species.

PMID- 11468814
TI  - Bioaccumulation and toxicity of four dissolved metals in Paracentrotus lividus
      sea-urchin embryo.
AB  - The bioaccumulation of four metals (Cd, Cu, Pb, Zn) dissolved in water was
      assessed measuring the concentrations recorded within sea-urchin larvae
      (Paracentrotus lividus, Lmk.) after a 48-h exposure period. Concurrently, the
      frequencies of abnormalities were evaluated at the 48-h pluteus stage to check
      the actual toxicity of such contaminants with regards to larval development.
      Maximum metal concentrations in the larvae reached 43.8 +/- 6.7 micrograms Cd g-1
      dry weight (d.w.), 1269 +/- 392 micrograms Cu g-1 d.w., 3106 +/- 679 micrograms
      Pb g-1 d.w., 534 +/- 62 micrograms Zn g-1 d.w. Bioconcentration factors (BCFs)
      reached very high values for Pb (maximum value: 16,282 +/- 973) and indicated
      that the concentrations of Pb and Cd were directly related to the water
      concentration at least in the range of concentrations tested. Zn appeared to be
      partially regulated above a certain threshold concentration (between 5 and 25
      micrograms l-1). Cu was accumulated with an active uptake at least below lethal
      threshold level (100 micrograms l-1). Nevertheless, above these thresholds, high
      mortality of embryos prevent any interpretation of Zn and Cu bioconcentration
      factors. Concurrent studies carried out on embryotoxicity confirmed the high
      toxicity of Cu towards sea-urchin pluteus larvae and highlighted the different
      behaviour of Cd. The internal Cd concentrations were directly related to the
      external ones, comparable to other non-essential metals, but Cd had little toxic
      effect on the initial larval development.

PMID- 11468815
TI  - Persistence of oiling in mussel beds after the Exxon Valdez oil spill.
AB  - Persistence and weathering of Exxon Valdez oil in intertidal mussel (Mytilus
      trossulus) beds in Prince William Sound (PWS) and along the Gulf of Alaska was
      monitored from 1992 to 1995. Beds with significant contamination included most
      previously oiled areas in PWS, particularly within the Knight Island group and
      the Kenai Peninsula. In sediments, yearly mean concentrations of total petroleum
      hydrocarbons ranged from < 60 micrograms/g in reference beds to 62,258
      micrograms/g wet wt., or approximately 0 to 523 micrograms/g dry wt. total
      polynuclear aromatic hydrocarbons (TPAHs). In mussels, mean TPAH concentrations
      ranged up to 8.1 micrograms/g dry wt. Hydrocarbon concentrations declined
      significantly with time in some, but not all mussels and sediments, and should
      reach background levels within three decades of the spill in most beds. In 1995,
      mean hydrocarbon concentration was greater than twice background concentration in
      sediments from 27 of 34 sites, and in mussels from 18 of 31 sites.

PMID- 11468816
TI  - Strong ligands for thorium complexation in marine bacteria.
AB  - The interaction between thorium and marine organisms (cultured heterotrophic
      bacteria) was experimentally examined by using chemical equilibrium techniques.
      Thorium (Th) quantitatively reacts with a binding site on bacteria (Alteromonas,
      Vibrio, Pseudomonas and Flavobacterium) in 0.1 M HCl solution. According to mass
      balance analysis of adsorption experiment data, Th forms a 1:1 complex with a
      binding site similar in reactivity among bacteria used in this study, whose
      conditional stability constants are in the range from 10(6.63) to 10(7.07) M-1
      under the experimental conditions of a 0.1 M HCl solution. The mole ratio of the
      strong ligand to organic carbon in bacteria ranged from 2.3 to 4.3 mmol/mol C.
      The strong ligand/carbon ratios in bacteria were more than one order of magnitude
      greater than in phytoplankton, zooplankton or other organic ligands in surface
      waters. The results suggest that the strong organic ligand reacting with Th is
      one of the functional groups commonly existing in oceanic microorganisms. The
      conditional stability constants of the Th complexes with the binding site in
      marine microorganisms are in the same order of magnitude as that with the strong
      ligand found in particulate and dissolved organic matter. These findings strongly
      suggest that the strong ligand in particulate and dissolved organic matter,
      reacting with trace metals under the conditions of seawater, originates from
      marine organisms.

PMID- 11468817
TI  - Can environmental isotopes help avoid a global water crises?

PMID- 11468818
TI  - Plutonium solubility in sediment pore waters.
AB  - Using in situ porous cup samplers, dissolved Pu concentrations have been measured
      over a year in the pore waters from two contrasting sites in the valley of the
      River Esk, North West England. In saltmarsh sediments, dissolved Pu represents
      approximately 1 part in 10(6) of the total inventory. The Pu concentration in
      solution is in the range 1.1-3.5 mBq l-1, varying by a factor of 3 in the course
      of the year. Most of the changes in dissolved Pu coincide with changes in
      dissolved Fe and Mn concentrations, with Pu being low in the summer months when
      Fe and Mn are high. Nevertheless, there are a number of factors which make it
      unclear as to whether these patterns might be related to seasonal redox changes
      in the saltmarsh. At the highly organic, reducing reedbed site, the proportion of
      Pu in solution is typically around 1 part in 10(3), proportionately much higher
      than in the saltmarsh, giving concentrations ranging between 9.0 and 28.5 mBq l
      1, and are apparently maintained by complexation to dissolved organic matter.
      There is no obvious seasonal pattern at the reedbed site nor is there any
      relation to any of the dissolved species measured (Fe, Mn, Na, DOC).

PMID- 11468819
TI  - Technetium-99 in the Irish marine environment.
AB  - Technetium-99 activity concentrations in seawater and biota from Irish coastal
      waters are presented. Time series measurements of 99Tc in seawater and Fucus
      vesiculosus from the western Irish Sea show that activity concentrations have
      increased in line with the increase in discharges of 99Tc from Sellafield. The
      peak in activity concentrations in both seawater and Fucus vesiculosus occurred
      in 1997 approximately two years after the peak in 99Tc discharges. The highest
      activity concentration recorded in Fucus vesiculosus showed a 29-fold increase
      over the mean concentration for the period 1988-1993. Technetium-99 activity
      concentrations were measured in fish, lobsters, prawns, mussels and oysters
      landed at major fishing ports on the east and northeast coasts of Ireland between
      1996 and 1998. Concentration factors for 99Tc in the brown seaweed Fucus
      vesiculosus and certain species of fish, crustaceans and molluscs from the Irish
      Sea were estimated. In general, these concentration factors were higher than
      those in the literature which were derived from laboratory studies, but agreed
      well with values which were based on field studies. The mean committed effective
      doses to Irish typical and heavy seafood consumers due to 99Tc in the period 1996
      1998 were 0.061 and 0.24 microSv, respectively.

PMID- 11468820
TI  - Soil contamination with 90Sr in the near zone of the Chernobyl accident.
AB  - Representative large-scale soil sampling on a regular grid of step width about 1
      km was carried out for the first time in the near zone of the Chernobyl accident
      (radius 36 km). An integrated map of terrestrial 90Sr contamination density in
      the 30 km exclusion zone (scale 1:200,000) has been created from the analysed
      samples. Maps of the main agrochemical characteristics of the soils, which
      determine the fuel particle dissolution rates and the contamination of
      vegetation, were produced. The total contents of 90Sr on the ground surface of
      the 30 km zone in Ukraine (without the reactor site and the radioactive waste
      storages) was about 810 TBq (8.1 x 10(+14) Bq) in 1997, which corresponds to 0.4
      0.5% of the Chernobyl reactor inventory at the time of the accident. This
      assessment is 3-4 times lower than previous estimates.

PMID- 11468821
TI  - The influence of clay mineralogy on the mobility of radiocaesium in upland soils
      of NW Italy.
AB  - 137Cs extraction experiments were performed on 14 contaminated soils from NW
      Italy with different characteristics and mineralogical composition. Solutions of
      HCl (pH = 0.5) and buffered EDTA/ammonium acetate (Lakanen solution) were used to
      assess bioavailability. The results show that less than 2% of 137Cs is available
      for leaching and/or root uptake. Even within a complex natural system it was
      possible to identify the amount of swelling clays (vermiculite + smectite) as the
      main control on Cs mobility under acidic conditions. The ammonium ion appears to
      be effective in desorbing Cs and its role is briefly discussed in terms of
      crystal chemistry. The relevance of mineralogy in assessing soil vulnerability is
      underlined.

PMID- 11468822
TI  - The presence of some artificial and natural radionuclides in a Eucalyptus forest
      in the south of Spain.
AB  - Long-lived artificial radionuclides (137Cs, 90Sr) were studied in a Eucalyptus
      plantation located in the south-west of Spain. Radionuclide concentrations were
      determined in different types of samples corresponding to specific forest
      components (soil, trees, herbs and litter). Depth profile distributions were
      obtained in two selected core soils. Two layers were separately measured in three
      other cores. The concentration factor, defined as the ratio between the mean
      activity concentration in a component and the mean activity concentration in the
      soil, was calculated for each component. The biomass of different components was
      estimated in order to evaluate the total density concentration (Bq/ha) of the
      artificial radionuclides (137Cs, 90Sr) in the Eucalyptus plantation. The transfer
      of the radionuclides between the different forest components can be inferred from
      the results. Additionally, other naturally occurring radionuclides (40K, 226Ra,
      228Ra, 228Ac) were determined for comparison. Transport of radionuclides from
      forest to a nearby pulp mill is also discussed.

PMID- 11468823
TI  - Radon progeny dose conversion coefficients for Chinese males and females.
AB  - The airway dimensions for Caucasian males have been scaled by multiplying by
      factors 0.95 and 0.88 to give those for Chinese males and females, respectively.
      Employing the most recent data on physical and biological parameters, the
      radiation doses to the basal and secretory cells due to alpha particles from
      218Po and 214Po, homogeneously distributed in the mucous layer, have been
      calculated. The emission of alpha particles has been simulated by a Monte Carlo
      method. For both basal and secretory cells, the dose conversion coefficients
      (DCCs) for physical conditions of sleep, rest, light and heavy exercise, have
      been obtained for Chinese males and females for unattached progeny, and for
      attached progeny of diameters 0.02, 0.15, 0.25, 0.30 and 0.50 micron. For basal
      cells, the coefficients lie in the range 0.69-6.82 mGy/(Js/m3) or 8.7-86 mGy/WLM
      for unattached progeny and in the range 0.045-1.98 mGy/(Js/m3) or 0.57-25 mGy/WLM
      for attached progeny. The corresponding ranges for Caucasian males are 1.27-8.81
      mGy/(Js/m3) or 16-111 mGy/WLM-1 and 0.05-2.30 mGy/(Js/m3) or 0.64-29 mGy/WLM. For
      secretory cells, the coefficients lie in the range 0.095-16.82 mGy/(Js/m3) (1.2
      212 mGy/WLM) for unattached progeny and in the range 0.095-6.67 mGy/(Js/m3) (1.2
      84 mGy/WLM) for attached progeny. The corresponding ranges for Caucasian males
      are 0.34-21.51 mGy/(Js/m3) (4.3-271 mGy/WLM) and 0.1-7.78 mGy/(Js/m3) (1.3-98
      mGy/WLM). The overall DCCs calculated for a typical home environment are 0.59 and
      0.52 mSv/(Js/m3) (7.4 and 6.5 mSv/WLM) for Chinese males and females,
      respectively, which are 80 and 70% of the value, 0.73 mSv/(Js/m3) (9.2 mSv/WLM),
      for Caucasian males.

PMID- 11468824
TI  - Adolescent parenthood: a costly mistake or a search for love?
AB  - Family life is changing worldwide and an increasing number of women are choosing
      single parenthood. Adolescents who become pregnant and early childbearers do not
      always become pregnant unintentionally; some actively plan pregnancy while others
      are ambivalent mainly about the timing. This paper reports on a study using an
      ethnographic approach that explored the mothering experiences of five sole
      supporting Australian teenage mothers who had a child over six months of age. It
      focuses on the story of one of them, a young woman who gave birth at 16 and set
      up home for herself and her son. Early childbearing is often a response to
      adverse social conditions such as poverty or homelessness and is not uncommonly
      chosen by teenage girls from socially deprived backgrounds. Educational and
      employment opportunities may be limited, whilst motherhood may provide a purpose
      in life when few other options are possible. Young women who make this choice
      need comprehensive services to support them in the parenting role, including
      appropriate health care, welfare and housing benefits, and support in dealing
      with parenting, a role which they may greatly desire but are not automatically
      well prepared for.

PMID- 11468825
TI  - Perspectives of adolescent boys on the risks of unwanted pregnancy and sexually
      transmitted infections: Kenya.
AB  - Sexual debut for boys in Kenya occurs mostly by mid-adolescence. This study looks
      at the perspectives of adolescent boys aged 15-19 attending schools in rural,
      eastern Kenya on the dual risks of unwanted pregnancy, STDs and HIV, based on
      qualitative data from eight focus group discussions with 90 boys. Despite a high
      knowledge of sexual risks, fear of HIV and awareness of the protective value of
      condoms, the young men exhibit high risk behaviour. They feel the need to conform
      to social prescriptions of male prowess, early sexual experience, and having more
      than one partner, yet their feelings about this behaviour are ambiguous and
      contradictory. They consider getting girls pregnant and having had a treatable
      STD as marks of masculinity, blame girls for not protecting themselves (and
      girls' parents), and want to boast about their sexual conquests to their peers.
      Yet they feel embarrassed and reticent about discussing sexual issues with
      adults, and are unwilling to get condoms from places where anonymity is not
      assured as they know their sexual activity is not sanctioned. There is a clear
      need for educational programmes that confront male sexual norms, address issues
      of gender power relations, promote communication skills, informed choice and
      sexual responsibility among boys as well as girls, and provide a consistent
      supply of good quality condoms free or at affordable prices.

PMID- 11468826
TI  - Adolescence--a dynamic concept.
AB  - The World Health Organization (WHO) defines adolescents as persons between 10 and
      19 years of age. (WHO 1998) Although adolescents make up about 20 per cent of the
      world's population (of whom 85 per cent live in developing countries), they have
      traditionally been neglected as a distinct target group and subsumed under the
      promotion of family, women's and child welfare and health. This has at least
      partially been because adolescents were seen as a relatively healthy age group,
      one that did not have a heavy 'burden of disease', at least as compared with
      young infants or older adults. However, there is increasing recognition that
      adolescents have special health-related vulnerabilities. Among the major causes
      of morbidity and mortality in young people are suicide, road accidents, tobacco
      use and sexual and reproductive ill-health. (WHO 1998) Furthermore, adolescents
      are increasingly seen as 'gateways to health' because behavioural patterns
      acquired during this period tend to last throughout adult life--roughly 70 per
      cent of premature deaths among adults are due to behaviours initiated in
      adolescence. (WHO 1998) This paper describes the social, economic, cultural,
      legal and health issues which affect the experience of adolescence. It shows that
      while young people around the world may experience the same physical changes and
      sensations during adolescence, the manner in which these are interpreted and give
      rise to social and legal prescriptions varies tremendously.

PMID- 11468827
TI  - Sexual behaviour and contraceptive use among unmarried, young women migrant
      workers in five cities in China.
AB  - This paper reports the results of exploratory research on reproductive and sexual
      health knowledge and sexual behaviour of young, unmarried women who migrate to
      cities from rural areas for work, and their access to and needs in relation to
      family planning in Beijing, Guangzhou, Shanghai, Guiyang and Taiyuan, in China.
      Focus group discussions were conducted with 146 young women aged 16-25 and 58 in
      depth interviews with key informants. Some of the young female migrant workers
      were sexually active and living with their boyfriends, most of whom expected to
      marry each other. Most of the women lacked basic information about reproduction
      and contraception, and did not know where or how to obtain contraception. There
      were social, psychological and economic barriers to accessing services. Only a
      small proportion of those who were unmarried were using contraception, so induced
      abortion was often the outcome of unprotected premarital sex. Pleasing male
      partners also played an important role in unprotected sex. The training,
      attitudes and approach of the entire family planning service system in relation
      to unmarried and young people in China, including this migrant population, needs
      to be reorientated so as to provide them with appropriate and adequate services.

PMID- 11468828
TI  - Perceptions of sexual coercion: learning from young people in Ibadan, Nigeria.
AB  - This study explored the problem of sexual coercion from the perspectives of 77
      young people aged 14-21 in Ibadan, Nigeria, the behaviours they perceive to be
      sexually coercive and the contexts in which these occur through four narrative
      workshops. Participants were drawn from two secondary schools and 15 apprentice
      workshops. All four groups identified similar coercive behaviours and developed
      narratives of the events that typically lead up to them. Behaviours included
      rape, unwanted touching, incest, assault, verbal abuse, threats, unwanted
      kissing; forced exposure to pornographic films, use of drugs for sedation and
      traditional charms for seduction, and insistence on abortion if unwanted
      pregnancy occurs. Men were typically the perpetrators and young women the
      victims. Perpetrators included acquaintances, boyfriends, neighbours, parents and
      relatives. All the narratives revealed the inability of young people to
      communicate effectively with each other and resolve differences. The results
      suggest the need for life-skills training that facilitates communication, seeks
      to redress gender power imbalances, teaches alternatives to coercion as a means
      of resolving conflict over sexual relations and respect for sexual and
      reproductive rights, and provides victims with information on appropriate
      services, support and referral.

PMID- 11468829
TI  - Views of Chinese parents on the provision of contraception to unmarried youth.
AB  - This study sought the views of Chinese parents on sex education and contraception
      for unmarried youth. Data were drawn from 16 focus group discussions conducted in
      eight sites in China in 1998-1999 with parents of unmarried children aged 18-24.
      While parents tended to recognise the reality of changing sexual norms, they were
      ambivalent with regard to sexual activity among young people and the provision of
      services to them. To prevent this ambivalence from posing a significant obstacle
      to the adoption of safe sex behaviours by young people, the dilemmas faced by
      parents need to be addressed through programmes for parents. Parents were clearly
      concerned for the well-being of their unmarried children, and keen to see their
      children protected from unwanted pregnancy and disease; they supported the
      provision of life skills education and the development of negotiation skills,
      self-esteem and the ability to exercise informed choice. Parents appeared willing
      for government to establish educational and service delivery programmes for the
      unmarried; it is important that government acts upon this.

PMID- 11468830
TI  - Self-aware sex education: a theoretical and practical approach in Venezuela.
AB  - Even a few decades ago, it was considered normal and even desirable in Latin
      America for young women to become pregnant before they were 20--provided they
      were married; while young men were expected to become sexually active as soon as
      they entered adolescence, without much concern about potential risks or with whom
      they did so--as long as it was a woman. This view is now changing. There seems to
      be a general consensus that 'education' is necessary to prevent adolescent
      pregnancy, abortion, STI/HIV and sexual abuse. Attempts to reach agreement as to
      what kind of education and where, and how and when to provide it often fail,
      however, because of the conflicting views of sexuality upon which they are based.
      This article discusses conflicting concepts of sexuality and describes the theory
      of critical pedagogy followed by AVESA, a Venezuelan NGO whose work focuses on
      sexuality, problems of sexuality and alternative sex education. It describes
      AVESA's practical experience in training youth promoters and running on ongoing
      youth education programme in sexual and reproductive health. AVESA advocates an
      educational alternative that builds self-awareness and a critical understanding
      of social reality. We encourage individuals to engage with their own history and
      circumstances in order to be able to experience their sexuality in a full,
      responsible, pleasurable and just manner.

PMID- 11468831
TI  - Challenges and dilemmas in counselling young women on pregnancy options.
AB  - This paper is about counselling young women up to 21 years of age who have an
      unintended pregnancy and need to decide whether to continue the pregnancy, have
      an abortion or give the baby up for adoption. What is important for a counsellor
      is to be able to respond appropriately to the issues they raise and support them
      to make a decision that they feel is right for them. Some young women know what
      they want to do and only need information to help them put this into effect.
      Others lean strongly towards one option or the other because it is what others
      want them to do, or is the opposite of what others want. Still other young women
      are unable to verbalise their feelings or opinions; they can be easily influenced
      by others and feel great indecision. During a counselling session, parents
      sometimes try to influence their daughter to make one decision or another. Some
      parents feel left out when their daughter will not discuss the pregnancy with
      them, and some bring up unrelated family problems. Counsellors need to
      acknowledge their own biases in working with young women, respond in ways that
      fit a young woman's level of development and acknowledge the difficulties parents
      sometimes have in coping with and responding to their daughter's situation.

PMID- 11468832
TI  - Socio-cultural aspects of menstruation in an urban slum in Delhi, India.
AB  - This paper attempts to understand the experience of menstruation in the socio
      cultural context of an urban Indian slum. Observations were gathered as part of a
      larger study of reproductive tract infections in women in Delhi, using both
      qualitative and quantitative methods. The qualitative phase consisted of 52 in
      depth interviews, three focus groups discussions and five key informant
      interviews. In the quantitative phase inferences were drawn from 380 respondents.
      Mean age at menarche was 13.5. Onset of menarche is associated with physical
      maturity and the ability to marry and reproduce. However, a culture of silence
      surrounds menarche, an event which took the women interviewed almost by surprise.
      Most were previously unaware that it would happen and the information they were
      given was sparse. Menstruation is associated with taboos and restrictions on
      work, sex, food and bathing, but the taboos observed by most of the women were
      avoidance of sex and not participating in religious practices; the taboo on not
      going into the kitchen, which had been observed in rural joint households, was
      not being observed after migration from rural areas due to lack of social support
      mechanisms. There is a clear need to provide information to young women on these
      subjects in ways that are acceptable to their parents, schools and the larger
      community, and that allow them to raise their own concerns. Education on these
      subjects should be envisaged as a long-term, continuous process, beginning well
      before menarche and continuing long after it.

PMID- 11468833
TI  - Working with public sector clinics to provide adolescent-friendly services in
      South Africa.
AB  - Health care facilities can play an important role for adolescents in preventing
      health problems, in promoting sexual and reproductive health and in shaping
      positive behaviours. Extensive research has established that South African public
      health facilities are failing to provide adolescent-friendly health services. The
      National Adolescent-Friendly Clinic Initiative (NAFCI) is an accreditation
      programme designed to improve the quality of adolescent health services at the
      primary care level and strengthen the public sector's ability to respond to
      adolescent health needs. The key objectives of the programme are to make health
      services more accessible and acceptable to adolescents, establish national
      standards and criteria for adolescent health care in clinics throughout the
      country, and build the capacity of health care workers to provide quality
      services. One of the indicators for success of NAFCI will be increased
      utilisation of public sector clinics by adolescents. NAFCI is an integral
      component of the largest, most innovative, public health programme ever launched
      in South Africa, loveLife. Achieving NAFCI accreditation involves clinic self
      appraisals, quality improvements, external assessments and award of achievement
      stars. NAFCI is currently being piloted in ten government clinics in South
      Africa.

PMID- 11468834
TI  - Sexually transmitted infections among adolescents: the need for adequate health
      services.
AB  - The World Health Organization (WHO) estimates that two-thirds of all STIs
      worldwide occur in young people--teenagers and those in their early twenties (WHO
      1993, WHO 1995). The provision of STI services to these age groups should
      therefore be high on the agenda of STI programme planners and adolescent/young
      people's health programmers alike. However, attempts to promote the sexual health
      of young people have so far tended to focus on prevention, education and
      counselling, while the provision of services to those who have already faced the
      consequences of unprotected sexual activity, including pregnancy and STI, or
      sexual violence, has lagged behind. In 1999-2000 a review was commissioned by GTZ
      of the characteristics of adolescent sexuality, evidence of STI risk in
      adolescents, the profile of adolescents in need of STI care, types and evidence
      of success of different STI service delivery models for adolescents and the
      advantages and disadvantages of each of these, and to what extent a youth
      specific approach to STI services or an STI-specific approach to adolescent
      health service delivery, is warranted. This review will be published jointly by
      GTZ and WHO with the title Sexually Transmitted Infections among Adolescents: The
      Need for Adequate Health Services. This is a shortened form of the Summary and
      Conclusions of this book.

PMID- 11468835
TI  - The need for youth-oriented policies and programmes on responsible sexuality in
      Argentina.
AB  - Since the mid-1990s, several provincial bills have been passed in Argentina
      mandating the creation of programmes for family planning and sexual health
      services and education. A National Plan for Integrated Health Care for
      Adolescents was also passed but resources and actual programmes remain limited.
      The policy process has been fraught with difficulties, owing to a strong alliance
      between the State and the Catholic church. Provision of contraceptives to
      adolescents has been one of the most contentious issues, as adolescents are
      legally minors and need parental permission to use family planning. NGOs are
      working with young people to help them to voice their perspectives and demands.
      The Programme for Responsible Sexuality was launched by the Province of Buenos
      Aires in 1999, in response to concrete demands on the part of poor communities
      for sexual and reproductive health services, including for young people. This
      Programme came to an abrupt end with the change of governor in that same year,
      illustrating the complexity of the policy-making process. These experiences
      demonstrate the urgency to develop strategies and set up task forces for
      effective advocacy of health and social programmes, and to make political leaders
      more aware of the social costs of refusing to support these.

PMID- 11468836
TI  - Exploring women's needs in an Amazon region of Ecuador.
AB  - This study broadly explored women's perceptions of their most pressing problems
      and needs in the mostly rural Amazonian province of Orellana in Ecuador in mid
      2000. In-depth interviews with community women and health and social service
      providers used two rapid structured, qualitative methods--free-listing and pile
      sorting--to explore the 'insider's' perspective, with the participation of local
      organisations, and generated discussion on the emerging issues, giving an
      opportunity for action aimed at improving women's situation. Unequal gender
      relations, subordination of women, economic problems, men drinking too much and
      domestic violence were identified as the most pressing concerns. Several
      reproductive and sexual health problems were also identified and information
      about others elicited. This paper describes the methodology used in the research,
      reports on the 20 most cited problems and looks more closely at the findings in
      relation to violence against women, lack of access to contraception and
      ambiguities arising from the need to resort to clandestine abortion. Despite the
      existence of innovative national policies related to domestic violence and
      reproductive health, there is a scarcity of resources and poor infrastructure in
      Orellana. Patronising attitudes on the part of health service staff also greatly
      limit women's access to reproductive and sexual health services.

PMID- 11468837
TI  - Youth statement to the African Development Forum.

PMID- 11468838
TI  - Ipas declines to sign the Global Gag Rule: public statement.

PMID- 11468839
TI  - Help! Our wombs are crumbling to pieces!

PMID- 11468840
TI  - Abortion law reform: the Turkish experience.

PMID- 11468841
TI  - Increasing mortality among young women in Afghanistan.

PMID- 11468842
TI  - Women's reasons for discontinuing contraceptive use within 12 months: Jamaica.
AB  - In Jamaica, contraceptive use is high at 66 per cent. However, only 34 per cent
      of pregnancies are planned. This study was carried out in 1998 to determine the
      factors which influenced continuation of use of family planning methods. Primary
      data were collected from 463 mostly post-natal women utilising eight large
      clinics in the public health sector in Kingston, Jamaica. They were interviewed
      using a closed-ended questionnaire three times over a year and a sub-sample
      participated in focus group discussions. The overall continuation rate was only
      56 per cent. Cost of methods was an issue for some women. Long clinic waiting
      times discouraged women from attending clinics; the scheduling of clinic
      appointments would reduce this problem. Women need more information about side
      effects of methods and to be reassured of the quality of methods given out by
      clinics. Health personnel need to become more aware of the significance of rumors
      about methods and discuss these with women so that the negative influence of
      misinformation is minimised. Although the findings of this study are not 'new'
      information, 'old' problems in the provision of services still exist. Women, at
      least in poorer communities, continue to lack basic information about
      contraceptives and there is a need for ongoing attention to improving quality of
      care.

PMID- 11468843
TI  - Gendered construction of sexual risks: implications for safer sex among young
      people in Kenya and Sweden.
AB  - This study compared perceptions of sexual risk and sexual practices among youth
      in Kenya and Sweden. Self-generated questions on the body, perceptions of sexual
      risk and sexual practices were collected in Kenya while focus group discussions
      and individual interviews on these same issues were used in Sweden. The most
      striking differences between the two countries were in the level of knowledge on
      matters of sexuality and the ability to talk with ease on these matters. The
      refusal in Kenya to provide adolescents with information and services has left
      the 'safe period' as their only protective option and pregnancy as the overriding
      concern. Communication at the partner level and lack of condom use are
      problematic in both countries and even where access to information and preventive
      services exist, these may not be used optimally. In both countries, boys had more
      sexual freedom, while girls were controlled through labelling and rumours, and
      girls were assigned responsibility for safer sex. We conclude that sexual
      education should be based more broadly on an understanding of the social norms
      defining sexual behaviour. It is at the level of sexual relations that the
      tensions between culturally-defined sexual and gender norms and public health
      assumptions should be addressed, a level at which health policy and education are
      silent in both countries.

PMID- 11468844
TI  - Single women's experiences of premarital pregnancy and induced abortion in
      Lombok, Eastern Indonesia.
AB  - Induced abortion is widely practiced in Indonesia by both married and unmarried
      women. This paper draws on ethnographic research, conducted between 1996 and
      1998, which focused on reproductive health and sexuality among young single women
      on the island of Lombok in Eastern Indonesia. While abortion for married women is
      tacitly accepted, especially for women with two or more children, premarital
      pregnancy and abortion remain a highly stigmatised and isolating experience for
      single women. Government family planning services are not legally permitted to
      provide contraception to single women and their access to reproductive health
      care is very limited. Abortion providers were highly critical of unmarried women
      who sought abortions, despite their willingness to carry out the procedure. The
      quality of abortion services offered to single women was compromised by the
      stigma attached to premarital sex and pregnancy. Women who experienced unplanned
      premarital pregnancy faced personal and familial shame, compromised marriage
      prospects, abandonment by their partners, single motherhood, a stigmatised child,
      early cessation of education, and an interrupted income or career, all of which
      were not desirable options. Young women were only able to legitimately continue
      premarital pregnancy through marriage. In the absence of an offer of marriage,
      single women necessarily resorted to abortion to avoid compromising their
      futures.

PMID- 11468845
TI  - Sexual initiation and childbearing among adolescent girls in KwaZulu Natal, South
      Africa.
AB  - A girl's first sexual intercourse is often unplanned and may put her at risk of
      STDs and HIV infection as well as unwanted pregnancy. The high prevalence of HIV
      among 15-24 year olds in KwaZulu Natal suggests that sex is initiated at an early
      age. This paper is based on a 1999 survey in South Africa which identified age of
      sexual debut and childbearing among adolescent girls in KwaZulu Natal. Of a
      sample of 796 girls, almost half had already had first sexual intercourse at a
      mean age of 16. Of these, 44 per cent reported having communicated with their
      first partner about preventing pregnancy, of whom 36 per cent were able to use a
      contraceptive method. The majority used a male condom, the pill or injectable.
      Similarly, 30 per cent had used a method, almost all of them a male condom, to
      prevent a sexually transmitted disease at first sex. About half of the girls had
      ever been pregnant and a large percentage of these indicated that the pregnancy
      had been unwanted. If sexuality education were to begin before puberty, at age 9
      10 and in primary school, then many more girls would be in a better position to
      make informed choices about their sexual activities by the time they begin to
      engage in sex or reach menarche.

PMID- 11468846
TI  - Reproductive health-seeking by married adolescent girls in Maharashtra, India.
AB  - In India, most adolescent girls 15-19 years old are married. A study was
      conducted in 1995-97 in Ahmednagar district of Maharashtra, India to gain insight
      into whether and how their reproductive health needs are met, especially for
      gynaecological problems, family planning and perceived fertility problems. It
      included a survey among 302 married girls of this age, and in-depth interviews
      with 74 girls, 37 husbands and 53 mothers-in-law. Girls were treated quickly for
      illnesses interfering with domestic work and were expected to conceive in the
      first year of marriage. Menstrual disorders and symptoms of reproductive tract
      infection often went untreated. There was an emerging need for delaying and
      spacing pregnancies; limiting the number of children was well established.
      Household work, protection of fertility and silence arising from embarrassment
      related to sexual health problems were the strongest factors influencing care
      seeking. Husbands made the decision whether their wives could seek care and
      mothers-in-law sometimes influenced these decisions; girls had neither decision
      making power nor influence. This study provides valuable input for the new
      reproductive and child health programme in Maharashtra.

PMID- 11468847
TI  - By and for young women and men.

PMID- 11468848
TI  - Understanding safe sex: gender narratives of HIV and pregnancy prevention by
      rural South African school-going youth.
AB  - In South Africa's HIV/AIDS epidemic, young people, especially women, are at high
      risk due to an apparent gap between awareness and practice. In repeated peer
      group discussions with girls aged 14-15 and boys aged 16-19, we explored
      influences on safe sex behaviour. Separate male and female safe sex paradigms
      emerged, with boys less likely to perceive themselves as 'at risk' and more
      likely to use condoms. Girls had not used condoms, would have preferred to delay
      sexual relationships and feared pregnancy as well as HIV/AIDS. Both sexes deemed
      it difficult for girls to initiate condom use, although both sexes viewed condoms
      favourably. Girls saw condoms as a sign of love and protection, whereas boys
      tended to use them with casual partners. A lack of decision-making autonomy
      within relationships further constrained girls' ability to practice safer sex.
      Involvement of peer participants in review of their own narrative data helped to
      ensure representation of participants' voices in the findings. Overall, these
      findings point to the need for programmes to address gender inequalities and
      emphasise behavioural skills in the years before sexual activity begins.

PMID- 11468849
TI  - From competition to community: participatory learning and action among young,
      debt-bonded Vietnamese sex workers in Cambodia.
AB  - Community mobilisation strategies for HIV/AIDS prevention based on recognition of
      social vulnerability and concepts of empowerment have emerged at the forefront of
      international efforts to reduce the AIDS pandemic, increasingly replacing a focus
      on individual risk. This paper describes the start-up phase of a participatory
      learning and action project to create a sense of community identity as a first
      step towards collective action among some 300 young, debt-bonded, brothel-based
      migrant sex workers from Vietnam in Phnom Penh, Cambodia. The factors that make
      sex workers vulnerable to HIV also pose considerable barriers to mobilising them,
      due to competing interests between and among brothel owners and sex workers.
      Discussion and visual tools--e.g. a spider diagram of causes of unsafe sex and
      how to overcome these--are being used in group work to analyse concerns expressed
      by sex workers, along with survey questionnaires and in-depth interviews. In the
      second phase the project will address sensitive topics such as violence and
      unsafe sex in more depth, in hopes of protecting the emerging solidarity among
      sex workers and shifting the balance towards greater co-operation.

PMID- 11468850
TI  - Unsafe sexual behaviour among schoolgirls in Mozambique: a matter of gender and
      class.
AB  - This study seeks to examine the reasons why young women aged 14-20 in Maputo,
      Mozambique were engaging in risky sexual behaviour, and to ascertain whether the
      spread of HIV is due to socioeconomic factors and/or patriarchal beliefs and
      mores, or both. It is based on in-depth interviews and questionnaires among 182
      girls in two secondary schools in Maputo, one attended primarily by working-class
      and one primarily by middle-class students. The findings suggest that while
      gender dynamics work against women overall, middle-class young women had fewer
      sexual partners, used condoms more often, seemed willing to challenge gender
      norms and were more assertive than their working class counterparts, which placed
      them at potentially more of an advantage in sexual negotiation. Working-class
      young women, for whom the interlocking categories of gender and class operated,
      were more accepting of gender power differentials, were less assertive and tended
      to be dependent on their partners for material needs more often, which served to
      weaken their bargaining power in relation to safe sexual behaviour and rendered
      them more vulnerable.

PMID- 11468851
TI  - Adolescent girls' life aspirations and reproductive health in Nepal.
AB  - The study described in this paper takes a participatory and positive approach to
      improving adolescent reproductive health in a rural and urban community in Nepal.
      It shows that adolescent girls in these communities have dreams and aspirations
      for a better future and that adults acknowledge and support these ideals.
      However, social norms and institutions are restrictive, especially for girls, who
      are often unable to realise their hopes for continuing education, finding better
      paid work or delaying marriage and childbearing, and this directly impacts
      reproductive outcomes. Insight into the broader context of adolescent girls'
      lives provides a valuable framework for designing positive programmatic actions
      which take as their entry point the disjuncture between girls' aspirations and
      realities. Interventions begun in these communities include youth clubs for safe
      social interaction and literacy classes; training of peer educators to teach life
      skills, including for married adolescents; forums for parents, teachers and
      health service providers to discuss their own concerns and those of adolescents;
      and work with the community to design programmes that will contribute to greater
      financial independence and employment opportunities for adolescents.

PMID- 11468852
TI  - Diverticular disease of the colon and laparoscopic surgery.

PMID- 11468853
TI  - Acute diverticulitis and diverticular disease of the colon: a safe indication for
      laparoscopic surgery.
AB  - AIM: We analyzed our experience with a laparoscopic method for the treatment of
      acute diverticular disease. METHODS: Between January 1994 and October 1999 a
      group of 52 patients who fulfilled the criteria for symptomatic diverticular
      disease in the descending and sigmoid colon underwent laparoscopy with resection
      of an average of 40 cm of the bowel. Intraabdominal mechanical anastomosis
      completed the procedure. RESULTS: The use of ultrasonic scissors made the
      laparoscopic technique easier and shortened operative time. Operative morbidity
      was 15%. Two patients with acute diverticulitis and associated sepsis were
      reconverted to open surgery, and 4 patients presented postoperative rectal
      bleeding which ceased spontaneously. No long-term complications were found except
      in 1 patient who developed an incisional hernia through an entry port. Oral
      intake began between the second and third day. Postoperative hospitalization was
      3-8 days (mean: 5.5 days) and mean operative time was 130 min (range: 70-240
      min). CONCLUSIONS: Despite the steep learning curve for this type of surgery, the
      good morbidity and mortality rates with the laparoscopic method, especially with
      high-risk groups of patients (age > 65 years, high blood pressure, etc.) suggest
      that this surgical option can be used efficiently and safely, and that it
      achieves better results than with open surgery. However, we feel that the
      treatment of patients with acute complications of diverticular colon disease
      requires extensive experience with laparoscopic colorectal surgery.

PMID- 11468854
TI  - Prognostic factors in Barrett's esophagus: an immunohistochemical and
      morphometric study of 120 cases.
AB  - Barrett's esophagus is a condition in which the squamous mucosa that normally
      lines the distal esophagus is replaced by a columnar type of epithelium. Although
      it carries a clear risk of adenocarcinoma, the estimation of this risk and
      therefore the value of endoscopic screening remain highly controversial. AIM: To
      investigate more sensitive techniques to identify those patients who are at high
      risk of developing cancer and who need intensive endoscopic surveillance for
      early detection. METHODS: A morphologic, histochemical and morphometric study was
      performed on paraffin-embedded material from 120 patients with Barrett's
      esophagus and 18 with adenocarcinoma. In addition, each sample was analyzed
      immunohistochemically with proliferating cell nuclear antigen (PCNA), p53, c-erbB
      2, CEA and EMA antibodies. RESULTS: In all zones of the glandular mucosa we found
      a higher percentage of PCNA-positive nuclei when the specialized epithelium was
      present. We saw PCNA expression in 75% of the patients with adenocarcinoma, and
      p53 expression in 15% of the patients without dysplasia, 37% of the patients with
      dysplasia and 44% of the patients with adenocarcinoma. Positivity for c-erbB-2
      was found in 38% of the patients without dysplasia, 53% of those with dysplasia
      and 37% of those with adenocarcinoma. Aneuploidy was found in 70% of the patients
      with metaplasia or dysplasia and in all patients with adenocarcinoma.
      CONCLUSIONS: We conclude that p53, PCNA overexpression and aneuploidy are markers
      of risk for malignancy in Barrett's esophagus.

PMID- 11468855
TI  - Effects of a tyrosine phosphatase inhibitor on chloride secretion in human
      intestinal epithelia.
AB  - AIMS: Transcellular chloride transport is the key event underlying epithelial
      hydration in the intestine. Little is known about the role of protein tyrosine
      phosphatases in the regulation of basal and stimulated secretion in human
      intestinal epithelia. The aim of our study was to investigate the effects of the
      protein tyrosine phosphatase inhibitor sodium orthovanadate on vectorial chloride
      transport in native human colon. METHODS: An electrophysiological technique was
      used to measure changes in short-circuit current via a dual voltage/current clamp
      in native human colon mucosa and in T84 (ATCC) human intestinal cells mounted in
      modified Ussing chambers. RESULTS: Orthovanadate (1 mM) added to the serosal side
      of native human colon caused a net rise in short circuit current, reflecting the
      stimulation of serosal-to-mucosal chloride movement. Epithelial cells responded
      similarly to the same concentration of the compound. The stimulatory effect of
      orthovanadate was enhanced by pretreatment with the tyrosine kinase inhibitor
      genistein, but only when orthovanadate was added to the basolateral chamber. In
      contrast, the synergistic interaction did not occur when epithelial cells were
      previously exposed to the cAMP agonist forskolin. CONCLUSIONS: We show that
      tyrosine phosphatases may be involved in the regulation of epithelial chloride
      transport, and that orthovanadate stimulates secretion in the human colon.

PMID- 11468856
TI  - Preoperative platelet count in pancreas cancer: a prognostic factor?
AB  - AIM: To determine whether preoperative platelet count influenced the prognosis
      for surgical treatment of pancreas cancer. METHODS: Retrospective study of 144
      patients operated on for pancreatic cancer: 49 with adenocarcinoma, operable with
      curative intent (group A), 86 in whom palliative resection or bypass was done
      (group B), and 9 in whom exploratory laparotomy was done. Preoperative platelet
      count was done for all patients. Groups A and B were divided into 2 subgroups (>
      200,000 platelets/mm3 and < 200,000 platelets/mm3), and an additional subgroup
      was established for patients with > 300,000 platelets/mm3. Survival was analyzed
      in the resulting subgroups. RESULTS: Among patients who underwent curative
      resection, statistical analysis revealed significantly better survival (p < 0.05)
      in patients with a platelet count > 200,000 platelets/mm3 and a very significant
      difference (p < 0.01) in the 300,000 platelets/mm3 subgroup. No differences were
      found in the subgroups of patients who underwent palliative surgery. CONCLUSION:
      Preoperative platelet count may represent a prognostic factor in patients with
      pancreatic cancer operated on with curative intent. Our findings justify the need
      for clinical trials of antiangiogenic therapy.

PMID- 11468857
TI  - [Informed consent in gastroenterology: inform first and then get the consent].

PMID- 11468858
TI  - [Antioxidants and pancreatitis: absence of randomization as well as of control
      group makes it impossible to draw any conclusion].

PMID- 11468859
TI  - [Economic evaluation of colorectal cancer screening with fecal occult blood
      detection].

PMID- 11468860
TI  - [Pancreatic toxicity of antimonials in patients with infections].

PMID- 11468861
TI  - [Gastrointestinal hemorrhage caused by a diffuse hemangiomatosis of the small
      bowel in an elderly patient].

PMID- 11468862
TI  - [Isolated elevation of aminotransferase. An atypical presentation of adult celiac
      disease].

PMID- 11468863
TI  - Provisions of learning experiences in the home and early childhood school
      readiness are clearly linked.

PMID- 11468864
TI  - Parent-child interaction in three conversational contexts: variations in style
      and strategy.

PMID- 11468865
TI  - Storybook reading and parent teaching: links to language and literacy
      development.

PMID- 11468866
TI  - The role of family and home in the literacy development of children from low
      income backgrounds.

PMID- 11468867
TI  - Emergent literacy is emerging knowledge of written, not oral, language.

PMID- 11468868
TI  - Beyond shared book reading: dimensions of home literacy and low-income African
      American preschoolers' skills.

PMID- 11468869
TI  - Long QT interval resembling long QT syndrome in a newborn with electrolyte
      dysbalance.
AB  - The Q-T interval by electrocardiogram may be prolonged as a congenital or
      acquired condition. The congenital form, long QT syndrome (LQTS) is an electrical
      disorder associated with a high mortality rate. However, in newborns, electrolyte
      abnormalities are one of the most common causes of a long Q-T interval. We
      describe a newborn with a prolonged Q-T interval (0.55 secs) and abnormal T waves
      resembling LQTS. In this case, the patient had an electrolyte disturbance which
      was effectively treated. This case emphasizes the importance of investigating and
      distinguishing between the congenital and acquired forms of prolonged Q-T
      intervals.

PMID- 11468870
TI  - Giant pulmonary cyst simulating tension pneumothorax.
AB  - Giant pulmonary cyst is a rare clinico-pathological entity. It was described as a
      "windy tumor" by John Floyer in 1726. Since that time, there have been numerous
      reports on this unique manifestation of emphysema by many authors. In this
      report, we report one such interesting case who was diagnosed as tension
      pneumothorax.

PMID- 11468871
TI  - Kentucky Board of Medical Licensure. Model guidelines for the use of controlled
      substances in pain treatment.
AB  - At its March 2001 meeting, the Kentucky Board of Medical Licensure adopted
      guidelines relating to physicians accepting gifts from industry, as well as
      guidelines for the use of controlled substances for the treatment of chronic
      pain. These guidelines were presented in a report to the KMA Board of Trustees
      during its April 4, 2001 meeting, and are being published in the Journal to
      assist physicians in dealing with these two important, but often confusing,
      issues. The report is being presented in two parts. The section relating to gifts
      to physicians was published in the June issue of the Journal. Guidelines on the
      use of controlled substances in treating chronic pain will be addressed in this
      issue.

PMID- 11468872
TI  - Managing patient expectations.

PMID- 11468873
TI  - Incidence and risk factors of preparation errors in a centralized cytotoxic
      preparation unit.
AB  - OBJECTIVE: A major objective of centralized preparation is to improve the quality
      of the final product, and thus their safety for the patient. Few data are
      available concerning errors occurring during preparation and the risk factors
      associated with the errors. To assess risk factors associated with preparation
      errors in a centralized cytotoxic preparation unit. DESIGN: Medication errors
      were detected during preparation (self-education by technicians) or at the time
      of control (qualitative and semi-quantitative). For each preparation, several
      potential risk factors were studied. Univariate analysis was carried out using
      Chi-2 or Fisher exact tests. Variables with p < 0.15 associated in univariate
      analysis were entered in a stepwise regression model. In an overall analysis, all
      types of error were considered. In a second analysis, only major errors (errors
      associated with drug, dose or major incompatibility) were studied. RESULTS:
      Analysis included 30,819 preparations. Overall and major error rates were
      respectively 0.45% and 0.19%. The number of bottles (more than one), the volume
      of active solution (more than 50 ml) and the daily workload were the major risk
      factors identified by successive univariate and multivariate analysis.
      CONCLUSION: Low rates of medication errors compared to previous studies were
      reported. Major preparation errors were principally related to drug labeling
      (dose/bottle and concentration) and workload. Preparation mistakes appeared to
      have many causes. These results could be used to revise the general organization
      and determine a suitable purchasing policy.

PMID- 11468874
TI  - Factors associated with non-response in proton pump inhibitor users: a study of
      lansoprazole therapy.
AB  - BACKGROUND: Proton pump inhibitors (PPI) demonstrate high healing rates of 85-98%
      in clinical trials. Due to the limited knowledge regarding response and non
      response to lansoprazole in daily practice and for the reason that resistance to
      PPIs is scarce, we investigated factors possibly associated with non-response.
      METHODS: Data were used from a prospective, open label, observational follow-up
      study in which 10,008 lansoprazole users were followed over time. The study was
      designed according to the SAMM guidelines. A matched nested case-control design
      was used to compare non-responding (cases) and responding (controls) lansoprazole
      users. Non-response was defined as worsening or non-improvement of symptoms at
      the first evaluation after at least 8 weeks of use, response as disappearance or
      improvement of symptoms within 8 weeks of use. Controls were matched for the
      evaluating physician. RESULTS: A total of 186 non-responders and 372 responders
      to PPI treatment were identified as cases and controls. Age of over 60 years,
      heavy smoking and previous use of PPIs were significantly more common in non
      responding patients compared with responding patients. There were no differences
      found between the reported diagnosis regarding response. CONCLUSION: In daily
      clinical practice, previous use of PPIs, heavy smoking and an age > 60 years were
      significantly associated with non-response to treatment with lansoprazole.
      Previous use of PPIs in non-responding patients might suggest resistance to PPIs.
      The knowledge that non-response drives non-response may encourage physicians to
      follow PPI users with previous PPI use more closely.

PMID- 11468875
TI  - Development of patient-centred performance indicators to guide the delivery of
      pharmaceutical care in a district general hospital.
AB  - The aim of this study was to audit clinical pharmacy practice in an acute
      hospital setting against the individual patient care guidelines set out in the
      CRAG "Framework for Practice" document, and then to develop practical, patient
      centred performance indicators that could be used locally to monitor the delivery
      of pharmaceutical care. A series of four audits were undertaken to establish key
      elements in the process of providing pharmaceutical care to patients. Four
      standard statements describing the performance of the pharmacy service in
      providing patient care were developed through peer discussion and formulation of
      ideas based around these data. The four standard statements were then used as
      performance indicators to evaluate service performance at PRI and tested by means
      of a further audit cycle. The use of this methodology facilitated operation of a
      structured service appraisal system and provided a forum that allowed problems
      with practice to be discussed and resolved.

PMID- 11468876
TI  - An evaluation of the use of proton pump inhibitors.
AB  - OBJECTIVES: To review whether Proton Pump Inhibitors (PPIs) are prescribed for
      appropriate indications and to assess the quality of information being supplied
      to GPs on discharge. METHOD: Prospective study of 85 patients consecutively
      admitted on, or initiated on, PPIs comparing prescribing patterns with the health
      authority consensus statement on PPIs and reviewing the quality of information
      provided to GPs on discharge. RESULTS: 39 patients were admitted on PPIs; 30% had
      absolute indications for prescribing, 3% had possible indications for prescribing
      and 67% were for indications other than those in the consensus statement. 46
      patients had PPIs initiated as inpatients; 39% had absolute indications for
      prescribing, 10% had possible indications for prescribing and 51% were for
      indications other than those in the consensus statement. 10% of patients admitted
      on PPIs had therapy reviewed prior to discharge, whilst 60% of patients initiated
      on PPIs during admission were reviewed prior to discharge. Information provided
      to GPs on discharge usually included dosage and frequency. 18% of discharge
      letters indicated the intended duration of therapy and 7% suggested a review
      date. For those initiated on PPIs as inpatients 51% of discharge letters gave an
      indication. CONCLUSION: Frequent review of therapy and improved communications
      between primary and secondary care are vital to rationalise the use of PPIs and
      to reduce expenditure.

PMID- 11468877
TI  - The dental implications of chronic use of acidic medicines in medically
      compromised children.
AB  - OBJECTIVE: Liquid oral medicines form a significant proportion (11%) of the
      medicines used by the population as a whole, either prescribed or over the
      counter. The active agent, as well as some of the other ingredients, can pose a
      threat to oral health. METHOD: Eight liquid oral medicines and two effervescent
      preparations routinely prescribed for long-term use by paediatric renal patients
      were assessed for titratable acidity and pH values. RESULTS: All of the medicines
      tested were acidic and the majority were well below the critical pH of 5.5 at
      which enamel demineralisation takes place. The titratable acidity values, at a pH
      of 6.7, ranged between 0.01 and 1.54 for the liquid preparations but were 8.4 and
      10.6 for the two effervescent tablets tested. CONCLUSION: Surplus acid in
      effervescent preparations while ensuring palatability of medicines and thus
      compliance, may produce unwanted dental side effects in children who are already
      medically compromised.

PMID- 11468878
TI  - Digestive hemorrhage caused by a Meckel's diverticulum in a metformin-treated
      patient: is there any connection?
AB  - An obese patient, not diabetic, treated with metformin for some weeks, was
      referred to us with severe inferior digestive hemorrhage, diagnosed with Meckel's
      diverticulum. Metformin is described as a glucose-lowering agent for treatment of
      type 2 diabetes mellitus and as antiobesity drug, though results achieved with
      this last indication are not conclusive. But metformin has fibrinolytic features
      by means of diminished plasminogen activator inhibitor 1 activity. Although no
      coagulation study was done and the Meckel's diverticulum is normally associated
      with bleeding, the particular intensity of the following hemorrhage may have been
      favored by metformin.

PMID- 11468879
TI  - Pre-emptive metoclopramide and ondansetron for nausea and vomiting associated
      with iloprost infusions.
AB  - OBJECTIVE: To assess the effectiveness of ondansetron in relieving symptoms of
      nausea and vomiting which were refractory to metoclopramide and cyclizine, in a
      patient receiving iloprost infusions. METHOD: Case observation in a series of 7
      infusions. RESULTS: Ondansetron reduced WHO symptom scores of vomiting from Grade
      2 to Grade 0. Symptoms of nausea were abolished on some occasions. CONCLUSION:
      Ondansetron was found to be effective at abolishing symptoms of vomiting and
      partially effective against symptoms of nausea. It may prove to be a useful
      treatment modality to allow the patient to tolerate further infusions of iloprost
      where nausea and vomiting has failed to respond to other agents.

PMID- 11468880
TI  - A splinter.

PMID- 11468881
TI  - Fluoroquinolone use and the change in incidence of tendon ruptures in the
      Netherlands.
AB  - INTRODUCTION: Shortly after their introduction, fluoroquinolones were associated
      with reports of tendinitis and tendon rupture. During the past years, the number
      of reports has risen, possibly because of an increased use of fluoroquinolones.
      In this study, we describe the use of fluoroquinolones in the Dutch community and
      the possible public health effects of an association between fluoroquinolone use
      and tendon ruptures. METHODS: In the PHARMO drug database we identified all
      prescriptions for fluoroquinolones in the period 1991-1996. The incidence of
      fluoroquinolone use was expressed as the number of fluoroquinolone episodes per
      1000 inhabitants in one year, and extrapolated to the Dutch population after
      standardisation on age and gender. The annual incidence of non-traumatic tendon
      ruptures in the period 1991-1996 was calculated with data from the nation-wide
      hospital registry. The expected number of fluoroquinolone attributable tendon
      ruptures was calculated on the basis of the use of fluoroquinolones, the number
      of non-traumatic tendon ruptures and an assumed relative risk of 1.5-10. RESULTS:
      In 1996, approximately 251,000 patients experienced 318,000 episodes of
      fluoroquinolone use in the Netherlands. Females used more often fluoroquinolones
      than males, and the number of episodes increased exponentially with age. In the
      period 1991 through 1996, the absolute number of fluoroquinolone episodes
      increased by 160%, from 122,000 to 318,000. The absolute number of hospitalised
      tendon ruptures increased with 28%, from 768 in 1991 to 984 in 1996. Assuming a
      relative risk of 1.5 to 10.0, 1 to 15 tendon ruptures could be attributed to
      fluoroquinolone use in 1996. Only 7% of the observed increase could be attributed
      to the increased use of fluoroquinolones. If the total increase of hospitalised
      non-traumatic tendon ruptures would be attributable to the increase in
      fluoroquinolone use, this would mean that the risk of non traumatic tendon
      ruptures to fluoroquinolones would be more than 250 times the risk during non
      use. CONCLUSION: In the Netherlands, a large simultaneous increase in non
      traumatic tendon ruptures and fluoroquinolone use was observed in the period
      between 1991 to 1996. Assuming a relative risk of 1.5 to 10.0 for tendon ruptures
      during fluoroquinolone use, only 0.5 to 7% of the increase in non-traumatic
      tendon ruptures could be attributed to the increased fluoroquinolone use. The
      increase in the incidence of non-traumatic hospitalised tendon ruptures in the
      Netherlands is not likely to be explained solely by the increased use of
      fluoroquinolones.

PMID- 11468882
TI  - Evaluation of vancomycin use in a large university-affiliated hospital in eastern
      France in 1999.
AB  - OBJECTIVE: In 1999, we conducted a retrospective drug utilization review to
      determine the volume and pattern of vancomycin use in a university-affiliated
      hospital in eastern France. METHODS: Total vancomycin use was determined and
      expressed as vancomycin courses per 100 admitted patients and defined daily doses
      (DDD) of vancomycin per 100 patient-days. The indication for vancomycin use was
      classified as appropriate or inappropriate according to the guidelines issues by
      the HICPAC. RESULTS: A total of 311 vancomycin courses were given, as 2098 DDD,
      giving crude incidences of 1.17 courses per 100 admitted patients and of 1.19
      defined daily doses per 100 patient-days. The frequency of appropriate courses
      was 66.7%. Of the 63 inappropriate courses of vancomycin, 39.7% and 28.6% were
      empiric therapy for nosocomial and community-acquired infections, respectively,
      20.6% and 6.3% were specific therapy for nosocomial and community-acquired
      infections, respectively, and 4.7% were prophylactic. CONCLUSIONS: This study
      shows that vancomycin use in our hospital resulted in a lower selection pressure
      than has been reported for US university-affiliated hospitals and that
      comprehensive programs to improve use of vancomycin are needed in our
      institution.

PMID- 11468883
TI  - Determinants of pharmacists' interventions linked to prescription processing.
AB  - AIM OF STUDY: The role of pharmacists in today's healthcare is changing rapidly.
      As they are close to the prescribing process, pharmacists are in the position to
      identify and adjust prescribing errors before dispensing. The objective of this
      study was to identify relevant determinants of interventions directly linked to
      prescription processing in community pharmacy. METHODS: As part of a yearly
      continuing education programme, all community pharmacies in the region of
      'Zealand' (N = 23) in the south-west of The Netherlands kept detailed records of
      all interventions directly linked to prescription processing during one week in
      May 1998. For every patient involved in an intervention, a control-patient was
      matched on pharmacy practice, date, gender and age. RESULTS: A total of 39,357
      prescriptions were evaluated by the 23 pharmacies during the one-week
      intervention programme. Out of these, one out of 10 resulted into an
      intervention. Being a first prescription in a new treatment episode was found to
      be a significant determinant (OR 1.75, 95 CI% 1.18-2.33). Variables reflecting
      drug therapy complexity (> 3 prescribers, > 15 prescriptions in 3 months before,
      > 3 different medications) showed all ORs higher than 1.00, but not significant.
      When looking at the individual drug categories, anti-infectives, respiratory
      drugs and cardiovascular medicines came out as important drug classes for
      intervention risk. We could not find any association between the number of
      signals per pharmacy and the number of interventions. CONCLUSION: The 'whistle
      blower' model of pharmacy based interventions is a valid one but needs a targeted
      and integral way of implemented thinking and use of information technology. In
      such an environment, interventions are a logical step of in-process quality
      control in the drug usage system.

PMID- 11468884
TI  - Nurses' need for knowledge inspires new column.

PMID- 11468885
TI  - Social isolation and sexual abuse among women who smoke crack.
AB  - The purpose of this study was to explore the prevalence of social isolation and
      its relationship to sexual trauma in a sample of Black women who smoke crack
      cocaine. Using a convenience sample of 115 Black women with a history of smoking
      crack cocaine, participants were interviewed for 2 to 4 hours and asked a variety
      of questions about their health, relationships, sexuality, and drug use.
      Bivariate and multivariate logistical regressions were used to predict whether
      the women reported being socially isolated. While social isolation was not
      necessarily a common experience among the sample, it was found that women who had
      been sexually abused were three times more likely to report being socially
      isolated than women who had not been sexually abused. In addition, social
      isolation was more common among women who had been abused by a family member, who
      had been abused when they were young, and who had been abused for a long period
      of time. However, multivariate analyses revealed that the age at which the sexual
      trauma occurred was the most salient predictor of social isolation in adulthood.
      Implications for drug treatment are discussed.

PMID- 11468886
TI  - Implementing medication algorithms. Role of behavioral health nurses.
AB  - 1. Clinical practice guidelines, also called algorithms, practice standards,
      protocols, and policies, are systematically refined parameters that guide
      decision making related to specific clinical disorders. 2. Algorithms and
      clinical practice guidelines were developed to provide a sequential framework for
      clinical decision making, improve quality of care, increase patient safety,
      control costs, and provide standardization of care. 3. While each format used to
      develop algorithms and clinical practice guidelines has advantages and
      disadvantages, the evidence-based format, in which an expert panel reviews
      evidence and designs the guidelines, which are then reviewed by practitioners and
      organizations in that clinical area, provides the most up-to-date and accurate
      guidelines. 4. As frontline caregivers in the behavioral health care system,
      nurses are in an ideal position to monitor patients' adherence and responses to
      clinical guidelines, including medication algorithms.

PMID- 11468887
TI  - A model of group treatment to facilitate recovery from chemical dependence.
AB  - In this article, a model of group treatment is proposed that incorporates four
      different group approaches (i.e., experiential, physiological-cognitive
      behavioral, mutual support, advocacy) sequentially to achieve recovery outcomes
      among people coping with chemical dependence. The model identifies two strategies
      (i.e., reflection and restoration, action and support) as overarching frameworks
      guiding the use of these four treatment approaches. The first strategy of
      reflection and restoration incorporates experiential and physiological-cognitive
      behavioral group approaches to promote precontemplation, contemplation,
      preparation, and tentative action among group members. The second strategy of
      action and support uses mutual support and advocacy approaches to help group
      members achieve and maintain treatment gains, learn from setbacks, and adopt new
      personal and social roles.

PMID- 11468888
TI  - Are you and your mental butler on good terms?

PMID- 11468889
TI  - Surgeon General addresses suicide prevention.

PMID- 11468890
TI  - Do breast cancer support programs make a difference?

PMID- 11468891
TI  - [The Freehand System: an implantable neuroprosthesis for functional
      electrostimulation of the upper extremity].
AB  - We report on the first experience with the Freehand system in German-speaking
      countries, an implantable neuroprosthesis developed for the functional electrical
      stimulation of the upper extremity. Indications for its use are neurological
      deficits of the cervical spinal cord with active mobility of the shoulder and
      elbow flexion in tetraplegics, ideally in C5/6 tetraplegics. A further
      precondition for the implantation of this system is an intact reflex arc of the
      muscles that are to be stimulated, i.e. of the forearm and hand. Central defects
      such as hemiparesis, cerebral palsies or athetoid disorders or peripheral nerve
      palsies (e.g. brachial plexus lesions) are no good indications for the
      implantation of the Freehand system. We report on patient selection criteria,
      preoperative percutaneous electrical stimulation, the surgical procedure itself
      with optional active tendon transpositions, the intensive postoperative
      rehabilitation program until the patient is able to use the system independently
      and the life-long after-care.

PMID- 11468892
TI  - [Further experiences with transplantation of the head of the fibula].
AB  - We are presenting our experience with vascularized epiphyseal transplantation of
      the upper end of the fibula, based distally on the anterior tibial artery in two
      patients, one suffering from septic epiphysitis of the hip with complete loss of
      the head and neck of the femur, the other suffering from radial club hand
      following septic loss of the radius, excluding its proximal and distal articular
      segments. In the first patient, the fibular epiphysis bridged the bone defect and
      provided growth at the neck of the femur. This restored hip stability, reduced
      limb-length discrepancy, initiated some degree of acetabular development, and
      maintained a functional range of hip motion. In the second patient,
      transplantation of the upper end of the fibula was used to bridge a gap resulting
      from complete resorption of the right radius and provide for growth of the
      radius. At follow-up, complete union of the graft was noted. The club-hand
      appearance improved markedly. Pronation and supination were regained. However,
      donor-site morbidity was a problem. It included sloughing of part of the peroneal
      muscles and the skin edge of the incision. This was due to loss of the anterior
      tibial artery as well as injury to the peroneal vessel collaterals supplying the
      skin and peroneal muscles. The latter occurred due to opening of the posterior
      compartment of the leg in an attempt to locate the anterior tibial artery at its
      origin from the popliteal artery. It is therefore concluded, that transplantation
      of the upper end of the fibula is a valuable reconstructive alternative for
      septic epiphysitis with complete loss of the head and neck of the femur as well
      as for septic loss of the radius. However, whenever an extended part of the upper
      end of the fibula needs being harvested, this should be performed through an
      anterior approach, in order to avoid sloughing of the skin and muscles of the
      anterior and lateral compartments of the leg.

PMID- 11468893
TI  - [Microtia: technique for external ear reconstruction with autologous rib
      cartilage].
AB  - Various methods for treatment of classic microtia are known. Beside a prosthesis,
      the most common way of auricle reconstruction is the use of autogenous rib
      cartilage; a process that requires two to three operations. In the first
      operation, rib cartilage is harvested from the 6th to the 9th rib. The base of
      the framework is the 6th and 7th rib cartilage which is taken under preservation
      of the synchondrosis. To mimic a 3-dimensional structure, the triangular fossa
      and scapha are carved into the groundplate and the 8th rib is fixed as a helical
      rim. After optimising the framework, it is placed in a subcutaneous pocket on the
      mastoid plane. In a second operation, approximately three months later, the
      auriculocephalic angle is reconstructed with a cartilage wedge, which is covered
      by a temporalis fascia flap and split skin-graft from the hairbearing skull.
      Commonly, a third operation is needed for minor refinements. Currently,
      autogenous rib cartilage is the ideal material available for ear reconstruction
      resulting in an excellent cosmetical outcome, although harvesting of the
      cartilage causes a specific donor-site morbidity. Operations improving the
      hearing ability by building up the external hearing channel and middle ear are
      mainly done in cases of bilateral microtia. Ear reconstruction with autogenous
      rib cartilage produces a replicable aesthetic result. The patients should be at
      least eight years old.

PMID- 11468894
TI  - [Does Epping resection arthroplasty lead to loss of hand strength? A prospective
      study].
AB  - FCR-sling resectional arthroplasty does not definitely prevent a proximalisation
      of the first metacarpal bone. Since power transmission of the thenar muscles
      requires a particular length of the thumb, does proximalisation lead to a
      reduction of grip strength of the hand? In a prospective study, hand-, key- and
      pinch-grip strength was compared to preoperative data. Pain intensity and thumb
      mobility were also examined. In comparison to preoperative data, the pain-free
      pinch grip improved 60% after three months and 100% after 12 months (p < 0.01).
      The maximum pinch grip improved 11% after three and 34% after 12 months (p <
      0.01). The pain-free key grip improved 22% after three months and 50% after 12
      months (p < 0.01). The maximum key grip showed a fair reduction after three
      months, but after 12 months the key pinch strength came up to preoperative level.
      The hand grip strength showed a statistically significant improvement of 9% after
      three months and 34% after 12 months (p < 0.01). After one year, 80% of the
      patients were completely painfree. There was no clinically relevant disturbance
      of thumb movement following surgery. Owing to proximalisation of the first
      metacarpal, a scapho-metacarpal distance of 5.3 (2-9) mm was measured. Despite
      proximalisation of the first metacarpal, a significant improvement of the grip
      strength was observed, which was rooted in simultaneous pain reduction.

PMID- 11468895
TI  - [Results of basal joint arthrosis treatment--comparison of Epping ligament
      reconstruction with trapeziectomy alone].
AB  - Objective of this study is to compare clinical and radiological results of two
      different methods of treatment for trapeziometacarpal osteoarthrosis of the
      thumb. Eighteen patients received operative treatment. An operation according to
      Epping was performed in eleven cases (collective I), while nine cases were
      treated with a trapeziectomy only (collective II). The mean follow-up of the
      first collective was 40 months and 15 months for the second one. The results of
      the two patient groups were subjected to statistical comparison in a
      retrospective study. This revealed no significant differences with regard to
      active range of motion, power, and subjective symptoms, classified according to
      the Buck-Gramcko score. With a mean of 49 points for the first and 50 points for
      the second collective, both achieved very good results. However, the mean
      operating time was significantly shorter in the patients treated with a
      trapeziectomy only, while the mean distance between the base of the first
      metacarpal bone and the scaphoid bone was significantly greater in this group.
      This is surely due to the shorter follow-up of the patients who underwent
      trapeziectomy only, since further proximalisation has to be expected. We were
      able to demonstrate that both methods yield equally good results, and hence the
      simpler technique of trapeziectomy alone should be given preference, at least in
      the standard situation of a patient, whose intermetacarpal ligaments offer
      sufficient stability after trapeziectomy.

PMID- 11468896
TI  - [Experiences with the STT (scapho-trapezio-trapezoid) arthrodesis. A
      retrospective evaluation].
AB  - From 1992 until 1998, 98 fusions of the scapho-trapezio-trapezoid joint on 97
      patients were performed in our clinic. The indications were dissociation of the
      scapho-lunate joint (n = 32), necrosis of the lunate stage III/IV (Lichtman
      classification) (n = 39), and idiopathic arthrosis of the scapho-trapezio
      trapezoid joint (n = 27). 87 patients with 88 procedures were reviewed after an
      average follow-up period of three years. The review included a clinical
      examination with determination of a traditional wrist-score and a DASH
      questionnaire, X-rays of the wrist and CT of the carpal bones. The results in the
      wristscore were on average 74 of maximal 100 points. The DASH-score was on
      average 29. The best results were in the group with arthrosis of the scapho
      trapezio-trapezoid joint. The results in the groups with scapho-lunate
      dissociation and necrosis of the lunate were also good. The rate of non-union was
      within an acceptable level with 7.7%. In the examined group, five patients
      underwent fusion of the wrist for persisting pain after scapho-trapezio-trapezoid
      arthrodesis. The examination of the radiological investigations in the reviewed
      group demonstrated, that CT shows arthritic degeneration in patients where the
      conventional X-ray does not. In conclusion, scapho-trapezio-trapezoid arthrodesis
      is a valid therapeutic method in the above mentioned indications. However, the
      question how early arthritic degeneration will affect long-term results remains
      unanswered for the moment.

PMID- 11468897
TI  - [Carpo-metacarpal dislocation injuries].
AB  - Carpometacarpal dislocations are rare. In most cases, the dislocation is caused
      by a violent injury, e.g. the crash of a motorcyclist or a fall from great
      height. A considerable swelling of the back of the hand may mask the
      characteristic lump at the root of the hand. The diagnosis can be easily missed
      due to serious associated injuries. The lesion is also often overlooked in the
      routine X-ray diagnostic. Lateral and oblique views are important for the
      recognition of the true extent of the lesion. Anatomical reposition is difficult
      if the dislocation is not fresh and open reposition is necessary. Between 1990
      and 1999, altogether 16 patients who had suffered a carpometacarpal dislocation
      were treated. One patient had a rare dislocation of the III. to V. joints.
      Simultaneous dislocation of all five carpometacarpal joints was seen in three
      cases. The treatment mostly consists of closed reduction and temporary Kirschner
      wire transfixation. Fourteen patients were controlled (clinical examination and X
      ray control) after an average follow-up time of three years. In addition, the
      DASH questionnaire was used. After an average time of 3 years the patients showed
      in 64% of the cases excellent and good results (eight excellent, one good). The
      subjective function of the hand was moderate in 29% (four patients), in one
      patient the subjective function was poor (7%). Five patients had a diminished
      range of motion of the hand. The average points in the DASH questionnaire were
      24. We recommend as therapy of choice after primary closed repositioning, primary
      surgery by means of short Kirschner wires introduced from distal-dorsal to
      proximal-palmar. In cases of impossible closed reduction or in cases with local
      additional injuries, open treatment for fixation, is indicated.

PMID- 11468898
TI  - [Long-term outcome of Swanson prosthesis management of the rheumatic wrist
      joint].
AB  - Silicone-wrist arthroplasty has dominated reconstructive surgery of the
      rheumatoid wrist for a long time. Silicone interposition wrist arthroplasty
      yielded good clinical results in short and midterm studies. The durability and
      longevity of the prosthesis however is limited and progressive X-ray
      deterioration and silicone synovialitis are the main shortcomings. We present the
      ten-year follow-up results of 102 rheumatoid wrists operated between 1984 and
      1992. 72 patients with 82 wrist arthroplasties were clinically and radiologically
      examined. The mean age at operation was 56.9 years. The average onset of R.A. was
      16.1 years. Each wrist was rated on a 100-point scale, with points based on wrist
      balance, range of motion, pain relief and extensor strength. The postoperative
      Clayton score averaged 69.4 points. Including revision cases, 51% of the Swanson
      implants were rated good or excellent, 16% fair, and 33% were judged poor because
      of pain or prosthesis breakage. Patient satisfaction and pain relief were
      achieved in 68.2%. Active motion with unrevised implants was 21 degrees extension
      and 31 degrees flexion. We noticed a moderate increase (7 degrees) for ulnar
      radial deviation. There was a progressive deterioration in the radiographic
      appearance. Implant fracture occurred in 31% of the patients. Subsidence of the
      implant and significant reduction of carpal height was noticed in 82.5% of the
      prosthesis. Revision procedures were performed in eleven cases. We conclude that
      the clinical and radiological results of Swanson silicone interposition
      arthroplasty will deteriorate with the passage of time. Beyond the potential
      deleterious effects of silicone, long-term radiological complications such as
      implant fracture, subsidence and carpal collapse are the main disadvantages of
      Swanson arthroplasty of the wrist. We therefore currently recommend the MPH-total
      wrist design in patients with rheumatoid arthritis.

PMID- 11468899
TI  - [Dorsal dislocation of the proximal interphalangeal joints of the finger. Results
      after static and functional treatment].
AB  - In a follow-up examination of 30 patients who had sustained dorsal dislocations
      of the PIP joint, the results of two conservative therapy regimens, either
      immobilisation or early motion were investigated. In Group A, 15 patients were
      treated by closed reduction and immobilisation with a forearm cast for four
      weeks. Nine patients showed normal range of motion, whereas a limitation of
      extension of ten degrees and more was seen in six cases. All PIP joints were
      stable. Nine patients were satisfied. Three patients complained of a limitation
      of extension, two of a limitation of extension and pain and one of swelling. In
      Group B, 15 patients were treated by dorsal block splinting of the PIP joint
      following reposition. The finger was released in extension with daily active
      exercise of the PIP joint. Only two of 15 patients showed limitation of
      extension, whereas 13 cases showed normal range of motion. Instability of one
      collateral ligament was seen in two cases. Palmar instability did not occur.
      Eleven patients were satisfied. One patient complained of instability, pain and
      lack of extension, one of pain in combination with instability, one of pain and
      one of swelling of the joint.

PMID- 11468900
TI  - [Effects of shaft length of finger joint prostheses on tension distribution in
      the bone].
AB  - In order to investigate the influence of stem length in finger joint prostheses
      on stress in the surrounding bone area, finite element (FEM) calculations of
      finger bones before and after prosthetic replacement of metacarpophalangeal
      joints with cementless implants of different stem length were performed. CT scans
      of the metacarpal bone and proximal phalanx before and after implantation of a
      prototype of a noncemented semiconstrained implant for the MP joint, which has
      been developed to replace metacarpophalangeal joints destroyed by rheumatoid
      arthritis, were analysed. The FEM calculations showed comparatively decreased
      differences of the von-Mises stress after implantation of intramedullary stems
      reaching the middle of the diaphysis. At the metaphysis of the metacarpal head we
      found an increase of the von-Mises stress of 1.3 MPa (Mega Pascal = 10(6) Pa), an
      increase of 18.9 MPa around the shortest prosthesis and a decrease of 21.4 MPa
      around the prosthesis with the longest stem.

PMID- 11468901
TI  - [Bone substitutes].

PMID- 11468902
TI  - [Foundation of the General Hospital: from charity to social order (1656-1666)].

PMID- 11468903
TI  - [Chronic respiratory insufficiency in France].
AB  - The data concerning the prevalence of chronic respiratory insufficiency (CRI) in
      France are scarce: in 1994 official numbers were 14,000 deaths due to chronic
      bronchitis, 2,000 due to asthma for a total number of 40,000 deaths with
      respiratory cause; the same year 27,000 new patients were compensated for chronic
      respiratory insufficiency by social security services. On January 1st 2000 the
      non-profit organizations was in charge of 21,500 patients with long term oxygen
      therapy and 10,500 with home ventilation, and the commercial companies
      respectively 30,000 and 6,000. Accordingly the total of patients treated at home
      for CRI is about 68,000. The repartition by cause of CRI, the characteristics of
      patients and the prognosis can be evaluated thanks to the ANTADIR observatory
      which collects medical data since 1981. Chronic obstructive pulmonary diseases
      (chronic bronchitis, emphysema, asthma, bronchiectasis) count for more than half
      of the total of cases. Other causes comprise pleuro-parietal diseases
      (tuberculosis sequelae, kyphoscoliosis), neuro-muscular diseases and interstitial
      lung diseases. CRI is a severe disease with a survival median of three years for
      chronic obstructive pulmonary diseases, and a prognosis slightly better for
      kyphoscoliosis and neuro-muscular diseases, and worse for pulmonary fibrosis.

PMID- 11468904
TI  - [Physiopathology of chronic respiratory insufficiency].
AB  - The host of chronic respiratory abnormalities responsible for an abnormal
      hematosis or for a handicap can be termed generically as chronic respiratory
      insufficiency. Hypoxemia can be the consequence of perturbations of oxygen
      transfer (fibrosis), of abnormal ventilation-perfusion ratios (venous admixture,
      chronic obstructive pulmonary disease [COPD]), or of hypoventilation
      (neuromuscular diseases). Hypercapnia can stem from hypoventilation
      (neuromuscular diseases), or from abnormal ventilation-perfusion ratios (dead
      space effect) (COPD). An imbalance between the capacity of the respiratory muscle
      to produce negative inspiratory pressures and the load they are faced with is a
      source of hypercapnia, and of dyspnoea and handicap independently of hematosis
      (COPD, neuromuscular diseases). The effects of hypoxemia on cellular functions
      make chronic respiratory insufficiency a systemic disease.

PMID- 11468905
TI  - [Diagnosis and evaluation of chronic respiratory insufficiency].
AB  - Chronic respiratory failure is defined by the inability of the respiratory system
      to carry out the gas exchange needed to fulfill the body needs. Its diagnosis is
      based on arterial blood gas measurements. It is possible, however, for the
      physician to assume it from clinical symptoms. Measuring peak expiratory flow
      allows one to evaluate the degree of insufficiency. The pneumologist confirms the
      diagnosis with arterial blood gases measurement and determines its severity.
      Exercise tests evaluate the incapacity. A quality of life questionnaire assesses
      the respiratory handicap resulting from the patient's life comfort deficit. After
      diagnosis, the respiratory failure follow-up is performed by the general
      practitioner, with specialized investigations as often as necessary according to
      the severity of the respiratory failure.

PMID- 11468906
TI  - [Indications for and modalities of long-term oxygen therapy].
AB  - Long-term oxygenotherapy treatment prevent pulmonary hypertension and
      hypercythemia in chronic hypoxic patients. LTOT is indicated in severe patients
      with a medial survival time of 3.5 years. Medical indication of LTOT is hypoxemia
      > 55 mmHg, or, if right cardiac sign or polycythemia are present PaO2 between 55
      and 60 mmHg. In some cases LTOT is used only during deambulation, if hypoxemia
      occurs only during activity. In most cases LTOT is received during all the night
      and as long as possible during the day time to reach 18 hours/24. OLT decreases
      the risk of polycythemia and pulmonary hypertension and increases the survival
      rate of chronic hypoxemic patients.

PMID- 11468907
TI  - [Modalities and indications for ventilation at home].
AB  - Home mechanical ventilation improved with as non invasive mechanical ventilation,
      not using endotracheal connection, which supplanted home mechanical ventilation
      with tracheostomy. Its main indication is chronic restrictive ventilatory failure
      with hypoxia and hypercapnia, the severity of which is revealed during an acute
      respiratory failure episode or through the apparition of diurnal signs of
      nocturnal hypoventilation. Its other indications are more controversial in
      obstructive respiratory failure, where long term oxygen therapy remains the first
      choice treatment, and where home mechanical ventilation is proposed when the
      disease worsens, with recurrent episodes of hospitalisation for acute
      decompensation.

PMID- 11468908
TI  - [Acute respiratory failure in patients with chronic respiratory insufficiency].
AB  - In the absence of severe clinical signs requiring endotracheal intubation, non
      invasive mechanical ventilation is the first-line treatment in patients with
      chronic respiratory insufficiency. For a patient with non-invasive support, the
      probability to avoid intubation is 2 or 3 times higher than for a patient
      initially treated by oxygen therapy alone. Oxygen therapy will remain the
      recommended approach for staff unfamiliar with non-invasive support. In chronic
      obstructive pulmonary disease (COPD) ventilated patients, keeping the intrinsic
      positive end-expiratory pressure to a minimum level decreases the risk of
      barotrauma. During exacerbation, in these patients, the 3 most often prescribed
      medications are inhaled bonchodilators, corticosteroids, and antibiotics. In
      addition to long term home oxygen therapy, the preventive measures include
      education of patients, pulmonary rehabilitation programs, and eventually routine
      use of ventilatory support in a home ventilatory setting.

PMID- 11468909
TI  - [Chronic respiratory insufficiency in the child].
AB  - Chronic respiratory insufficiency in childhood can be caused by a heterogeneous
      group of diseases whose management and prognosis differ. Bronchopulmonary
      dysplasia in infants, and cystic fibrosis and neuromuscular diseases in older
      children, represent the most common causes of chronic respiratory insufficiency.
      The improvements in medical treatments, with the development of long term oxygen
      therapy and non invasive mechanical ventilation, have contributed to the
      increased survival and the better quality of life of these children. An objective
      evaluation of treatments, such as long term oxygen therapy and non invasive
      mechanical ventilation, are warranted to improve the indications and benefits of
      these therapies.

PMID- 11468910
TI  - [The challenge of home care for respiratory failure].
AB  - In France, 65,000 patients with chronic respiratory failure are managed at home.
      This is made possible by the collaboration between prescribing physicians and
      other medical and social agents in the community. It consists in various medical,
      technical and social interventions, all aimed at improving both survival and
      quality of life. Patient and family education is a key-factor to increase the
      success of the various therapeutic interventions that are rehabilitation, long
      term oxygen therapy and home mechanical ventilation. Rehabilitation programmes
      include optimisation of pharmacological treatments, help in smoking cessation,
      social and psychological support, and exercise training. National alert procedure
      for medical devices, and evaluation of medical devices is part of the management
      of respiratory failure at home. Care networks facilitate the various
      interventions necessary to maintain the patient with chronic respiratory failure
      at home.

PMID- 11468911
TI  - [Medical development: conflict of interest?].

PMID- 11468912
TI  - [Nevrotic syndrome: phobic neurosis].

PMID- 11468913
TI  - [Pregnancy and diabetes (including gestational diabetes). Diagnosis,
      complications, principles of treatment].

PMID- 11468914
TI  - [Anemia. Diagnostic approach].

PMID- 11468915
TI  - [Epilepsy in the adult. Etiology, diagnosis, prognosis, treatment].

PMID- 11468916
TI  - [Epilepsy in the child. Etiology, diagnosis, prognosis, treatment].

PMID- 11468917
TI  - [Mitral valve stenosis. Physiopathology, diagnosis].

PMID- 11468918
TI  - State and local retirement plans: innovation and renovation.
AB  - This Special Report/Issue Brief examines the universe of state and local
      retirement plans. It describes how these plans have developed and continue to
      evolve in a number of areas, including plan features, regulatory framework,
      governance, and asset management. While these retirement programs differ in many
      respects from private-sector plans, the disparity in some areas has narrowed.
      This report also includes a discussion of trends and the underlying forces for
      change. Public-sector retirement programs provide an important source of pension
      coverage in the United States, and are a significant part of the total retirement
      market: Combined public-sector retirement assets (state, local, and federal
      governments) comprised 29 percent of the $11.2 trillion U.S. retirement market in
      1998. State and local plans are dominant in the public-sector retirement market,
      holding $2.7 trillion in assets, compared with $696 billion held by federal plans
      (both military and civilian). More than 16 million individuals are employed by
      state and local jurisdictions in the United States. State and local retirement
      plans share certain common features because of the environment in which they
      operate. Legal statutes, governance, and tradition all play a role in defining
      what is sometimes referred to as a "public-sector culture." Despite common
      features, there is considerable diversity among public-sector retirement plans.
      To attract and retain a skilled work force, public-sector employers have
      increased their use of defined contribution (DC) plans to supplement defined
      benefit (DB) plans (or, to a lesser extent, replace or serve as an alternative to
      them) and improve cost-of-living adjustments. At the same time, a combined
      federal-state regulatory framework has encouraged certain plan design features,
      unavailable in the private sector, which include multiple tiers for successive
      generations of employees in a single plan and different strategies to increase
      portability. State and local retirement plans reflect an increasing role by the
      federal government in pension system design and operation, which has led to
      greater complexity in such areas as Social Security participation and deferred
      compensation arrangements. Complexity can be expected to increase with the recent
      passage of P.L. 107-16, the Economic Growth and Tax Relief Reconciliation Act of
      2001. The latest full-year data included in this report are for 1999 and in some
      cases 2000. After this report went to press, the Federal Reserve issued
      significantly revised quarterly data for state, local, and federal retirement
      plan assets, which were not incorporated in this Issue Brief.

PMID- 11468919
TI  - China's dugongs.

PMID- 11468920
TI  - Managing coastal bathing water quality: the contribution of microbiology and
      epidemiology.
AB  - The EU Bathing Water Directive with a life of 25 years (EEC, 1976) has
      contributed significantly to the improvement of the quality of coastal
      recreational waters throughout Europe and has successfully protected public
      health. Improvement of the standards of living and general public demands has
      made it necessary to consider updating it (EU, 1994) introducing important
      changes in microbiological parameters. Measurement of microbial pollution is of
      primary importance to this new proposal, as is to the regulatory schemes
      introduced by the very recent 'Annapolis Protocol' (WHO/US EPA, 1999). This
      report discusses the microbiological aspects of the health-related management of
      bathing seawater in the context of the scientific information available from
      epidemiological and microbiological studies.

PMID- 11468921
TI  - Dispersion and toxicity to non-target aquatic organisms of pesticides used to
      treat sea lice on salmon in net pen enclosures.
AB  - Pesticides are used extensively in the finfish aquaculture industry to control
      sea lice infestations on farmed salmon. The most prevalent method of use is to
      enclose a net pen with an impervious tarpaulin and mix a pesticide solution
      within that enclosure. After treatment for short periods (1 h) the pesticide
      solution is released to the environment. Concerns have been raised that there is
      a potential risk to non-target aquatic organisms from those releases. The fate of
      dispersing pesticide solutions was measured after six simulated treatments in the
      Lower Bay of Fundy, New Brunswick. Three simulated treatments were done with
      azamethiphos and three with cypermethrin. Rhodamine dye was added to all
      pesticide solutions in order to facilitate tracking of the dispersing plume
      through real-time measurements of dye concentrations by a flow-through
      fluorometer coupled with a differential global positioning system (DGPS). Water
      samples were obtained from within the plumes at various times after release and
      analysed for pesticide content and toxicity to a benthic amphipod Eohaustorius
      estuaris. Dye concentrations were detectable for time periods after release which
      varied from 2 to 5.5 h. Distances travelled by the dye patches ranged from 900 to
      3000 m and the dye concentrations at the final sampling period were generally
      1/200-1/3000 the pre-release concentrations and cypermethrin concentrations were
      generally 1/1000-1/2000 the pre-release concentrations. Cypermethrin
      concentrations in water samples were closely correlated with dye concentrations,
      indicating that dye analyses were an accurate surrogate for cypermethrin
      concentrations. Most samples taken after the releases of azamethiphos were not
      toxic to test organisms in 48 h exposures and none were beyond 20 min post
      release. By contrast, almost all samples taken after the release of cypermethrin,
      even up to 5-h post-release, were toxic. Data indicate the potential to cause
      toxic effects over areas of hectares from a single release of cypermethrin.

PMID- 11468922
TI  - Hydrocarbon contamination of coastal sediments from the Sfax area (Tunisia),
      Mediterranean Sea.
AB  - The coastal area off the city of Sfax (730,000 inhabitants), well-known for
      fisheries and industrial activities, receives high inputs of organic matter
      mostly anthropogenic. Eighteen stations were selected in the vicinity of the
      direct discharge of industrial sewage effluents in the sea in order to study the
      spatial distribution of the organic contamination. Surface sediments sampled in
      the shallow shelf were analysed for hydrocarbons by Fourier transform infrared
      spectroscopy, gas chromatography and gas chromatography/mass spectrometry. Total
      hydrocarbon distributions revealed high contamination as compared to other
      coastal Mediterranean sites, with an average concentration of 1865 ppm/dry weight
      sediment. Gas chromatographic distribution patterns, values of unresolved
      mixture/n-alkane ratio and distributions of steranes and hopanes confirmed a
      petroleum contamination of the Arabian light crude oil type. Biogenic compounds
      were also identified with a series of short-chain carbon-numbered n-alkenes in
      the carbon range 16-24.

PMID- 11468923
TI  - Evidence for polychlorinated biphenyls dechlorination in the sediments of Sado
      Estuary, Portugal.
AB  - Sediment gravity cores and grab samples were collected in the Sado Estuary and in
      its coastal area. The cores were sliced on board and the percentage of weight
      loss on ignition was determined in the laboratory, and analysed for
      polychlorinated biphenyl (PCB) congeners. PCB contents were higher in samples
      from the North Channel of the estuary, nearby the industrial zone (max. 114 ng g
      1 dry weight), while levels in the coastal area were lower than 4.9 ng g-1. The
      concentrations of the quantified congeners varied irregularly with sediment depth
      in the estuary, but showed two opposite distribution patterns in cores from the
      coastal area: the proportions of lower chlorinated congeners increased with
      depth, while congeners with higher number of chlorines decreased. This suggests a
      dechlorination of the most chlorinated congeners into less toxic compounds, under
      reductive conditions of the sediment. Though measurements were done in natural
      environment it appears that dechlorination was not entirely dependent on chlorine
      position in the phenyl rings.

PMID- 11468924
TI  - The effect of ship scrapping industry and its associated wastes on the biomass
      production and biodiversity of biota in in situ condition at Alang.
AB  - The main pollutants for the ship scrapping industry and its associated wastes at
      Alang are heavy metals, petroleum hydrocarbon and bacterial contaminations. The
      concentration of iron, manganese, cobalt, copper, zinc, lead, cadmium, nickel and
      mercury were 25 to 15,500% more at nearshore station of Alang as compared to
      control site at Piram. The concentration of heavy metals in the nearshore station
      of Alang was always higher than its concentration at 10 km away. The
      concentration of petroleum hydrocarbon was 16,973 and 53,900% more at the
      nearshore and 10 km away respectively at Alang as compared to controls. The
      concentration of chlorophyll-a and phaeophytin were in non-detectable range (<
      0.2 and < 0.1 mg m3) or much lower concentration at both the stations of Alang as
      compared to controls. The total viable count, total coliform, Escherichia coli,
      Vibrio cholerae, Vibrio parahaemolyticus and other Vibrio, Streptococcus
      faecalis, Shigella, Salmonella, Proteus, and Klebsiella were always higher (17%
      605%) at the nearshore station of Alang as compared to control. Similar trend was
      observed at 10 km away from Alang. Bacteria in sediment also showed the same
      pattern of variation. Phytoplankton counts at the nearshore station and 10 km
      away from Alang were only slightly raised. In contrast to phytoplankton, the
      zooplankton showed considerable reduction of growth (-10 to -66%) at Alang.

PMID- 11468925
TI  - Flood defence in the Blackwater Estuary, Essex, UK: the impact of
      sedimentological and geochemical changes on salt marsh development in the
      Tollesbury Managed Realignment site.
AB  - Recent changes in the UK's coastal defence strategy have resulted in the
      introduction of Managed Realignment (MR), a technique which attempts to establish
      salt marshes on low-lying coastal farmland. This work investigates the impact of
      MR, in particular on the interactions between sediment movement, changes in heavy
      metal concentrations and salt marsh development. Pre- and post-inundation samples
      were collected and analysed between 1995 and 1997. Sediment transport patterns
      (1996) demonstrated that sediment particles were distributed by tides around the
      site, resulting in a change in the spatial distribution of the metals which was
      related to the sediment particle size distribution. Despite the presence of some
      metal contaminants found within the MR site, vegetated salt marsh has developed
      since 1997. However, heavy metals such as Cu, Mn, Ni, Pb and Zn exhibited
      relative depletion in the sediment developing with salt marsh in 1997, which is
      in agreement with data indicating that concentrations of metals within sediments
      is related to frequency of tidal inundation. During initial development of the
      site, sediment transport was the main factor controlling metal distribution,
      however, subsequently the frequency of tidal inundation became the most
      significant factor. Further work may allow for prediction of how future MR sites
      will develop with respect to redistribution of sediments and subsequent transport
      of contaminants in the dissolved phase.

PMID- 11468926
TI  - Trace metals in estuarine sediments from the southwestern Spanish coast.
AB  - The impact of river-transported metal pollution and industrial wastes on the
      metal distribution (Cr, Cu, Zn, Pb) in estuarine sediments was studied in the
      southwestern Spanish estuaries. Intertidal and subtidal surface sediments of the
      Tinto-Odiel Estuary are very highly polluted by heavy metals, with
      geoaccumulation indices up to 4 in the three sedimentary environments studied
      (channel, channel border and salt marsh). The single exception is the Punta
      Umbria channel, very protected from the point sources by salt marsh deposits and
      hydraulic processes. In the remaining two estuaries, pollution (Pb, Cu) was only
      significant near the harbour situated in the Piedras river mouth, whereas very
      low values were found in the Guadiana Estuary. In these last rivers, the
      enrichment factor increases from the channel to the salt marsh sediments.

PMID- 11468927
TI  - Gulfwatch: monitoring spatial and temporal patterns of trace metal and organic
      contaminants in the Gulf of Maine (1991-1997) with the blue mussel, Mytilus
      edulis L.
AB  - Gulfwatch, established in 1991, is an international contaminant monitoring
      program in which the blue mussel, Mytilus edulis, is used as an indicator of the
      level and extent of contamination in the Gulf of Maine. Since 1991, trace metals,
      PAHs, PCBs, and OC pesticides have been measured in mussel tissues at 56 sites.
      The distribution of most metals was relatively uniform throughout the Gulf with
      the exception of Ag, Pb and Cr. However, the concentration of organic
      contaminants increased in a north-to-south direction. High concentrations of
      contaminants were correlated with large human population density and proximity to
      large rivers. Temporal analysis of five sites revealed that the majority of
      contaminant concentrations were either unchanged or decreasing. The
      concentrations of most contaminants were lower than the median of the National
      Status and Trends (NS & T) Mussel Watch with the exceptions of Cr, Hg, Pb and
      sigma PCB24. Hg concentrations at > 80% of the Gulfwatch sites exceeded the NS &
      T median +1 SD. Gulfwatch continues as a primary contaminant monitoring program
      in the Gulf of Maine.

PMID- 11468928
TI  - Improved sea ice parcel trajectories in the Arctic via data assimilation.
AB  - An assimilated sea ice motion product is used to track ice parcels in several
      regions of the Arctic over time periods of one day to several weeks during 1992
      1993. Motions simulated using a two-dimensional, dynamic-thermodynamic sea ice
      model are combined with motions derived from daily 85 GHz special sensor
      microwave/imager (SSM/I) imagery using an optimal interpolation method that
      minimizes error covariance. Assimilation attenuates the tracking error over the
      stand-alone model in comparison to buoy trajectories with the same starting
      location and time. The average 14-day assimilated trajectory's displacement error
      is as much as 34% lower than the model trajectory, while the RMS direction error
      is decreased by up to 10 degrees (24%). Assimilation can also yield an estimate
      of dispersion, which is not retrievable by point buoy observations. An
      assimilation approach improves estimates of ice drift and has the potential to
      further the understanding of ice mass flux, freshwater flux, and pollutant
      transport in the polar regions.

PMID- 11468929
TI  - Livestock wastewater treatment by a mangrove pot-cultivation system and the
      effect of salinity on the nutrient removal efficiency.
AB  - The present investigation compared the capacity of greenhouse pot-cultivation
      systems under two salinity conditions (freshwater and saline water) with two
      mangrove species (Bruguiera gymnorrhiza and Kandelia candel) to remove nutrients
      from livestock wastewater. During the whole treatment period there were
      relatively stable leachate TOC concentrations for wastewater-treated pots.
      Leachate NH4(+)-N concentration of B. gymnorrhiza pots was generally lower than
      that of K. candel pots. Leachate PO4(3-)-P concentration of pots receiving
      wastewater under freshwater condition was higher than that under saline water
      condition. Soil inorganic N content was more than two times higher for the
      wastewater treatments than that for the controls under low salinity condition and
      slower rate of increase under saline water condition. Soil P nutrients of both
      total and extractable inorganic forms significantly increased for both systems
      due to the discharges of livestock wastewater under both salinity conditions. The
      rate of increase in P contents for plants receiving livestock wastewater was 1-4
      times that of the controls, much more than that in N contents (0.04-1.30 times).
      N nutrient removal efficiencies were 84.3% (65.6% by soil and 18.7% by plant) and
      95.5% (32.2% by soil and 63.4% by plant), respectively by Kandelia candel and B.
      gymnorrhiza pot-cultivation systems under freshwater condition. Under saline
      water condition, N nutrient removal efficiencies by K. candel and B. gymnorrhiza
      pot-cultivation systems were 92.7% (80.7% by soil and 12.0% by plant) and 98.0%
      (67.6% by soil and 30.3% by plant), respectively. P nutrient removal efficiencies
      by K. candel and B. gymnorrhiza systems under freshwater condition were 79.2%
      (76.6% by soil and 2.6% by plant) and 91.8% (88.2% by soil and 3.6% by plant),
      respectively. The corresponding values were 88.0% (84.2% by soil and 3.8% by
      plant) and 97.8% (95.9% by soil and 1.9% by plant) under saline water condition.

PMID- 11468930
TI  - Metals and organochlorines in pelagic cetaceans stranded on the coasts of England
      and Wales.

PMID- 11468931
TI  - Measuring behaviour in developmental disability: a review of existing schedules.

PMID- 11468932
TI  - Use of dental services by 26-year-old New Zealanders.
AB  - The use of dental services and its oral-health associations were investigated in
      a birth cohort of 26-year-olds in order to examine the oral health and health
      care effects of the change in entitlement to State assistance for dental care
      which occurs when the eighteenth birthday is reached. Fewer than half were
      routine users, and this proportion was greater among females. More of those who
      were episodic users at age 26 rated their oral health poorly, and more than one
      in six had had a tooth extracted since age 18 because of caries. Those who used
      dental services only when they had a problem not only had greater caries
      experience by the age of 26, but also their caries increment over the previous 8
      years was also greater. Visiting the dentist for routine check-ups was associated
      with better long-term oral-health consequences than only going when there was a
      problem.

PMID- 11468933
TI  - The use of cross-sectional spiral tomography in the placement of implants.
AB  - Spiral tomography has been in use at the School of Dentistry, University of
      Otago, for 3 years. During this time over 140 examinations for radiographic
      workup prior to installation of implants have been undertaken. The cross
      sectional spiral modality has proved to be of particular value for accurate
      assessment of bone. Its technical capabilities offer higher image quality
      compared with linear tomographic or computerised tomographic images. Imaging can
      be completed in one session, with minimal inconvenience to the patient and
      minimal radiation dose. High-quality images provide accurate information,
      contributing significantly to the long-term success of osseointegrated implants.

PMID- 11468934
TI  - Aspects of professional development of orthodontists in New Zealand.
AB  - Strategic planning, service development, and management by objective are
      approaches usually associated with corporate business. However, the New Zealand
      Association of Orthodontists (NZAO) is using them successfully in responding to
      the rapidly changing legislative, professional, and commercial environment in
      this country. This report gives an account of an initiative taken by NZAO in
      response to such changes to strengthen the professional development of practising
      orthodontists in New Zealand. This involved setting up a group within the
      Association to organise a meeting on a key issue in clinical orthodontics, using
      a workshop format to promote discussion and debate in place of the passive
      reception of information characteristic of most professional meetings. It also
      sought to test the feasibility of having a live keynote presentation via video
      teleconference link from a speaker in the United States.

PMID- 11468935
TI  - Oranga niho: current issues in Maori dental health.

PMID- 11468936
TI  - Bite injuries: pathophysiology, forensic analysis, and management.
AB  - Bites are serious injuries that constitute 1 percent of all emergency-department
      visits in the United States of America. Human bite injuries may lead to loss of
      function, infection, and gross disfigurement, and often are associated with
      interpersonal and sexual violence, and child abuse. Issues with infection from
      oral contaminants, tissue damage, and difficult surgical reconstruction make the
      management of human bite injuries a challenge. The unique nature of teeth and the
      bite marks they produce are invaluable in forensic pathology. A systematic and
      detailed evaluation of bite injuries should be performed by a forensic
      odontologist in order to provide the necessary information for forensic purposes.
      Management of human bite injuries includes wound debridement, surgery to repair
      or replace damaged tissue, and long-term antibiotic therapy.

PMID- 11468937
TI  - Periodontitis in a 13-year-old.

PMID- 11468938
TI  - A mechanism-based pharmacokinetic model for the cytochrome P450 drug-drug
      interaction between cyclophosphamide and thioTEPA and the autoinduction of
      cyclophosphamide.
AB  - Cyclophosphamide (CP) is widely used in high-dose chemotherapy regimens in
      combination with thioTEPA. CP is a prodrug and is activated by cytochrome P450 to
      4-hydroxycyclophosphamide (HCP) which yields the final cytotoxic metabolite
      phosphoramide mustard (PM). The metabolism of CP into HCP exhibits autoinduction
      but is inhibited by thioTEPA. The aim of this study was to develop a population
      pharmacokinetic model for the bioactivation route of CP incorporating the
      phenomena of both autoinduction and the drug-drug interaction between CP and
      thioTEPA. Plasma samples were collected from 34 patients who received high-dose
      CP, thioTEPA and carboplatin in short infusions during 4 consecutive days.
      Elimination of CP was described by a noninducible route and an inducible route
      leading to HCP. The latter route was mediated by a hypothetical amount of enzyme.
      Autoinduction leads to a zero-order increase in amount of this enzyme during
      treatment. Inhibition by thioTEPA was modeled as a reversible, competitive,
      concentration-dependent inhibition. PM pharmacokinetics were described by first
      order formation from HCP and first-order elimination. The final models for CP,
      HCP, and PM provided an adequate fit of the experimental data. The volume of
      distribution, noninducible and initial inducible clearances of CP were 31.0 L,
      1.58 L/hr and 4.76 L/hr, respectively. The enzyme amount increased with a zero
      order rate constant of 0.041 amount * hr-1. After each thioTEPA infusion,
      however, approximately 80% of the enzyme was inhibited. This inhibition was
      reversible with a half-life of 6.5 hr. The formation and elimination rate
      constants of PM were 1.58 and 0.338 hr-1, respectively. The developed model
      enabled the assessment of the complex pharmacokinetics of CP in combination with
      thio TEPA. This model provided an adequate description of enzyme induction and
      inhibition and can be used for treatment optimization in this combination.

PMID- 11468939
TI  - Assessment of actual significance levels for covariate effects in NONMEM.
AB  - The objectives of this study were to assess the difference between actual and
      nominal significance levels, as judged by the likelihood ratio test, for
      hypothesis tests regarding covariate effects using NONMEM, and to study what
      factors influence these levels. Also, a strategy for obtaining closer agreement
      between nominal and actual significance levels was investigated. Pharmacokinetic
      (PK) data without covariate relationships were simulated from a one compartment
      i.v. bolus model for 50 individuals. Models with and without covariate
      relationships were then fitted to the data, and differences in the objective
      function values were calculated. Alterations were made to the simulation
      settings; the structural and error models, the number of individuals, the number
      of samples per individual and the covariate distribution. Different estimation
      methods in NONMEM were also tried. In addition, a strategy for estimating the
      actual significance levels for a specific data set, model and parameter was
      investigated using covariate randomization and a real data set. Under most
      conditions when the first-order (FO) method was used, the actual significance
      level for including a covariate relationship in a model was higher than the
      nominal significance level. Among factors with high impact were frequency of
      sampling and residual error magnitude. The use of the first-order conditional
      estimation method with interaction (FOCE-INTER) resulted in close agreement
      between actual and nominal significance levels. The results from the covariate
      randomization procedure of the real data set were in agreement with the results
      from the simulation study. With the FO method the actual significance levels were
      higher than the nominal, independent of the covariate type, but depending on the
      parameter influenced. When using FOCE-INTER the actual and nominal levels were
      similar. The most important factors influencing the actual significance levels
      for the FO method are the approximation of the influence of the random effects in
      a nonlinear model, a heteroscedastic error structure in which an existing
      interaction between interindividual and residual variability is not accounted for
      in the model, and a lognormal distribution of the residual error which is
      approximated by a symmetric distribution. Estimation with FOCE-INTER and the
      covariate randomization procedure provide means to achieve agreement between
      nominal and actual significance levels.

PMID- 11468940
TI  - Efficient screening of covariates in population models using Wald's approximation
      to the likelihood ratio test.
AB  - We propose an efficient algorithm for screening covariates in population model
      building using Wald's approximation to the likelihood ratio test (LRT) statistic
      in conjunction with Schwarz's Bayesian criterion. The algorithm can be applied to
      a full model fit of k covariate parameters to calculate the approximate LRT for
      all 2k - 1 possible restricted models. The algorithm's efficiency also permits
      internal validation of the model selection process via bootstrap methods. We
      illustrate the use of this algorithm for both model selection and validation with
      data from a Daypro pediatric study. The algorithm is easily implemented using
      standard statistical software such as SAS/IML and S-Plus. A SAS/IML macro to
      perform the algorithm is provided.

PMID- 11468941
TI  - In vivo-in vitro correlation (IVIVC) modeling incorporating a convolution step.
AB  - The purpose of in vivo-in vitro correlation (IVIVC) modeling is described. These
      models are usually fitted to deconvoluted data rather than the raw plasma drug
      concentration/time data. Such a two-stage analysis is undesirable because the
      deconvolution step is unstable and because the fitted model predicts the fraction
      of a dosage unit dissolved/absorbed in vivo which generally is not the primary
      focus of our attention. Interest usually centers on the plasma drug concentration
      or some function of it (e.g., AUC, Cmax). Incorporation of a convolution step
      into the model overcomes these difficulties. Odds, hazards, and reversed hazards
      models which include a convolution step are described. The identity model (which
      states that average in vivo and in vitro dissolution/time curves are coincident
      or directly superimposable) is a special case of these models. The odds model and
      the identity model were fitted to data sets for two different products using
      nonlinear mixed effects model fitting software. Results show that the odds model
      describes both data sets reasonably well and is a significantly better fit than
      the identity model in each case.

PMID- 11468942
TI  - Population pharmacokinetic analysis and optimization of the experimental design
      for mizolastine solution in children.
AB  - Mizolastine is a second generation antihistamine agent approved in Europe for the
      treatment of allergic rhinitis and skin conditions for which Sanofi-Synthelabo is
      developing a pediatric solution. Our objective was to design the population
      pharmacokinetic (PK) study of mizolastine pediatric solution in children. A
      bioavailability study of this solution compared to the marketed tablet was
      performed in 18 young volunteers. These PK data were analyzed by nonlinear
      regression using a two-compartment open model with zero-order absorption. From
      the estimated parameters, we designed population PK studies in two groups of
      children: 6 to 12 years and 2 to 6 years, respectively. To compare several
      population designs and to derive the optimal ones, we used the determinant of the
      Fisher information matrix of the population characteristics using a first-order
      expansion of the model. We have evaluated a "reference" population design with 10
      samples (from 0.25 to 36 hr after drug intake) per child in 6 children, which
      could not be implemented in practice for ethical reasons. We then derived optimal
      population designs with 1, 2, 3, 4, or 5 samples per child and a total of 60
      samples. Finally, the designs that were implemented in the population PK study
      were "compromise" population designs with 60 samples; one defined for 20 children
      6 to 12 years old, and one with 24 children 2 to 6 years. In the older group, the
      population design involved 8 children with a catheter from which 6 samples at
      time 0.25, 0.5, 0.75, 2, 3, and 6 hr after drug intake are collected, and 12
      children with only one sample at time 8, 12, 24, or 36 hr. In the younger group,
      the population design involved 15 children with a catheter who are divided in
      three groups with four samples at different times from 0.25 to 6 hr after drug
      intake, and 12 children with only one sample at time 8, 12, 18, or 24 hr. The
      expected average increase of variances of these designs compared to the reference
      design were 1.6 and 1.8 for the older and younger group, respectively, which was
      decided to be acceptable. Better population designs would have involved three
      groups of children with five samples per child but could not be implemented in
      practice. The data of the PK study in children 6 to 12 years were available and
      were analyzed using NONMEM. A total of 53 concentrations were obtained in 18
      children. The same two-compartment model with zero-order absorption was used. The
      interindividual variability in children was small. The estimated population
      parameters in children 6 to 12 years, were 0.28 L/kg for Vc/F, 0.10 L/hr per kg
      for CL/F, 0.53 hr-1 for lambda 1, 0.076 hr-1 for lambda 2, and 0.49 hr for Tabs.
      These values were close to the median values observed in young volunteers when
      standardized to 70 kg; notably, CL/F in L/hr per kg was similar, so that a dose
      of 0.15 mg/kg o.d. for mizolastine pediatric solution should give an equivalent
      area under the curve to a 10 mg o.d. tablet in adults.

PMID- 11468943
TI  - Acute muscle spasm.

PMID- 11468944
TI  - Just a family doc.

PMID- 11468945
TI  - Exploring the actions of vitamin C.

PMID- 11468946
TI  - The abortion issue.

PMID- 11468947
TI  - No more eyeball jugglers, please.

PMID- 11468948
TI  - Improving the quality of discharge summaries.

PMID- 11468949
TI  - The evolution of methicillin-resistant Staphylococcus aureus in Canadian
      hospitals: 5 years of national surveillance.
AB  - BACKGROUND: To better understand the epidemiology of methicillin-resistant
      Staphylococcus aureus (MRSA) in Canadian hospitals, surveillance has been
      conducted in sentinel hospitals across the country since 1995. We report the
      results of the first 5 years of the program. METHODS: For each newly identified
      inpatient with MRSA, medical records were reviewed for demographic and clinical
      data. Isolates were subjected to susceptibility testing and molecular typing by
      pulsed-field gel electrophoresis. RESULTS: A total of 4507 patients infected or
      colonized with MRSA were identified between January 1995 and December 1999. The
      rate of MRSA increased each year from a mean of 0.95 per 100 S. aureus isolates
      in 1995 to 5.97 per 100 isolates in 1999 (0.46 per 1000 admissions in 1995 to
      4.12 per 1000 admissions in 1999) (p < 0.05). Most of the increase in MRSA
      occurred in Ontario, Quebec and the western provinces. Of the 3009 cases for
      which the site of MRSA acquisition could be determined, 86% were acquired in a
      hospital, 8% were acquired in a long-term care facility and 6% were acquired in
      the community. A total of 1603 patients (36%) were infected with MRSA. The most
      common sites of infection were skin or soft tissue (25% of MRSA infections),
      pulmonary tissues (24%) and surgical sites (23%); 13% of the patients were
      bacteremic. An epidemiologic link with a previously identified MRSA patient was
      suspected in 53% of the cases. Molecular typing indicated that most (81%) of the
      isolates could be classified as related to 1 of the 4 Canadian epidemic strains
      of MRSA. INTERPRETATION: There has been a significant increase in the rate of
      isolating MRSA in many Canadian hospitals, related to the transmission of a
      relatively small number of MRSA strains.

PMID- 11468950
TI  - Availability of antidotes at acute care hospitals in Ontario.
AB  - BACKGROUND: Acutely poisoned patients sometimes require immediate treatment with
      an antidote, and delays in treatment can be fatal. We sought to determine the
      availability of 10 antidotes at acute care hospitals in Ontario. METHODS: Mailed
      questionnaire with repeated reminders to pharmacy directors at all acute care
      hospitals in Ontario. RESULTS: Responses were obtained from 179 (97%) of 184
      hospitals. Only 9% of the hospitals stocked an adequate supply of digoxin immune
      Fab antibody fragments, a life-saving antidote for patients with severe digoxin
      toxicity, whereas most of the hospitals stocked sufficient supplies of ipecac
      syrup (88%) and flumazenil (92%), arguably the least crucial antidotes in the
      survey. Only 1 hospital stocked adequate amounts of all 10 antidotes. Certain
      hospital characteristics were associated with adequate antidote stocking
      (increased annual emergency department volume, teaching hospital status and
      designation as a trauma centre). Conversely, antidote supplies were particularly
      deficient at small hospitals and, paradoxically, geographically isolated
      facilities (those most reliant on their own inventory). The cost of antidotes
      correlated only weakly with stocking rates, and many examples of excessive
      antidote stocking were identified. INTERPRETATION: Most acute care hospitals in
      Ontario do not stock even minimally adequate amounts of several emergency
      antidotes, possibly jeopardizing the survival of an acutely poisoned patient.
      Much of this problem could be rectified at no additional cost by reducing
      excessive stock of expensive antidotes and redistributing the resources to
      acquire deficient antidotes.

PMID- 11468951
TI  - Stopping short the spread of methicillin-resistant Staphylococcus aureus.

PMID- 11468952
TI  - Hazards of systemic steroids for ventilator-dependent preterm infants: what would
      a parent want?

PMID- 11468953
TI  - Boundary crossing: the physician and the photographer.

PMID- 11468954
TI  - Hospital medicine in Cambodia: a visiting doctor's perspective.

PMID- 11468955
TI  - Rheumatology: 15. Osteoporosis.

PMID- 11468956
TI  - Global doubts.

PMID- 11468957
TI  - Variant Creutzfeldt-Jakob disease: a summary of current scientific knowledge in
      relation to public health.
AB  - The prion diseases pose unique scientific, medical, veterinary and regulatory
      challenges. Here, we summarize current information bearing on the natural
      history, pathobiology and epidemiology of these disorders and public policy
      responses to the potential threats to public health posed, particularly, by
      bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease (vCJD).
      Six years after the first case reports of vCJD, there is still no clear
      indication of the magnitude of the primary epidemic, or of the likelihood of
      lateral transmission of this untreatable disease by iatrogenic means,
      particularly by blood and blood products. However, the unsettling nature of the
      available evidence warrants prudence regarding public health policy and
      regulation, as well as a forward-looking approach to research.

PMID- 11468958
TI  - A policy analysis of major decisions relating to Creutzfeldt-Jakob disease and
      the blood supply.
AB  - Creutzfeldt-Jakob disease (CJD) is the first major challenge that the blood
      system has faced since the completion of the Krever inquiry in 1997. We report
      the results of a detailed policy analysis comparing 2 CJD-related decisions: a
      1995 recall of blood from a donor with classic CJD and the 1999 decision to defer
      donations from individuals with a 6-month travel history to the UK between 1980
      and 1996 due to concerns related to variant CJD. Overall, we observed that
      decision-making improved significantly from 1995 to 1999. In 1998/99 the
      potential threat of variant CJD was identified at an early stage, and a
      systematic risk assessment process was initiated. Decision-making was
      consultative and involved consumers. However, the perception existed that further
      improvement could take place in the areas of transparency of process and
      interaction of organizations. We observed that the presence of a second operator
      had an important impact on decision-making in 1998/99.

PMID- 11468959
TI  - Cloning in Canada? Don't hold your breath.

PMID- 11468960
TI  - Anesthesia the sleeper in 2001 residency match.

PMID- 11468961
TI  - Drug-facilitated date rape.

PMID- 11468962
TI  - Miconazole-warfarin interaction: increased INR.

PMID- 11468963
TI  - Rosiglitazone (Avandia): hepatic, cardiac and hematological reactions.

PMID- 11468964
TI  - Adverse drug reaction reporting--2000: Part 2.

PMID- 11468965
TI  - Influence of sample manipulation on contaminant flux and toxicity at the sediment
      water interface.
AB  - Toxicities of sediments from San Diego and San Francisco Bays were compared in
      laboratory experiments using sea urchin (Strongylocentrotus purpuratus) embryos
      exposed to pore water and at the sediment-water interface (SWI). Toxicity was
      consistently greater to embryos exposed at the SWI to intact (unhomogenized)
      sediment samples relative to homogenized samples. Measurement of selected trace
      metals indicated considerably greater fluxes of copper, zinc, and cadmium into
      overlying waters of intact sediment samples. Inhibition of sea urchin embryo
      development was generally greater in sediment pore waters relative to SWI
      exposures. Pore water toxicity may have been due to elevated unionized ammonia
      concentrations in some samples. The results indicate that invertebrate embryos
      are amenable to SWI exposures, a more ecologically relevant exposure system, and
      that sediment homogenization may create artifacts in laboratory toxicity
      experiments.

PMID- 11468966
TI  - The organochlorine contamination history of the Mersey estuary, UK, revealed by
      analysis of sediment cores from salt marshes.
AB  - Sediment profiles in the Banks, Ince and Widnes Warth salt marshes in Northwest
      England contain a mappable record of historic pollution. For persistent
      organochlorine compounds this stretches back over 90 years. The PCB and HCH
      profiles can be successfully rationalised by dating methods, and they can be
      related to the dates of initial production and subsequent withdrawal from use of
      these chemicals as a result of restrictive environmental legislation. HCB has a
      more complex pollution profile as it has been manufactured in Northwest England,
      both deliberately as a pesticide and accidentally as a by-product of several
      chlorination processes, dating back to the start of the 20th century. The
      concentrations of degradation products of DDT are relatively constant through the
      sediment profile and are dominated by op'- and pp'-DDD with only minor
      contributions from the most toxic species, pp'-DDT. The quantities of these
      compounds resident in the reservoir of pollutants under these marshes have been
      calculated, and have fallen progressively in the last 30-50 years.

PMID- 11468967
TI  - Changes in zoobenthic community structure after pollution abatement from fish
      farms in the Archipelago Sea (N. Baltic Sea).
AB  - Long-term changes in sediment macrofauna communities at two sites affected by
      fish farming in the Archipelago Sea, south-west Finland have been investigated.
      Sampling stations in the Sarkansalmi Strait and Kaukolanlahti Bay, previously
      investigated 1982-1991, were revisited in 1994, 1995 and 1998 to detect signs of
      recovery following a decrease in organic load since 1990 and 1991, respectively.
      The results indicate a partial recovery in Sarkansalmi during post-pollution
      years, whereas no improvement has taken place in Kaukolanlahti. The improvement
      in Sarkansalmi is shown by a significant increase in the number of species and
      total abundance, and by the community structures becoming more similar over time.
      On the other hand, a significantly decreased number of species, abundance and
      biomass values over time as well as the occurrence of defaunated anoxic
      sediments, are clear signs of continued deterioration in Kaukolanlahti.
      Differences in the recovery potential of the two water areas are interpreted as
      consequences of topography and water exchange patterns causing differences in
      oxygen saturation.

PMID- 11468968
TI  - Acute toxicity of five sediment-associated metals, individually and in a mixture,
      to the estuarine meiobenthic harpacticoid copepod Amphiascus tenuiremis.
AB  - The acute effects of many individual, seawater-solubilized metals on meiobenthic
      copepods and nematodes are well known. In sediments, however, metals most often
      occur as mixtures, and it is not known whether such mixtures exhibit simple
      additive toxicity to meiobenthos. The estuarine meiobenthic copepod Amphiascus
      tenuiremis was tested in four acute (96-h) sediment bioassays to determine
      sediment and pore-water LC50s for single-metal exposures to copper (Cu), lead
      (Pb), nickel (Ni) and zinc (Zn). Laboratory-cultured copepods were exposed to
      clean 98% silt:clay sediments spiked with metal chloride solutions to yield five
      exposure concentrations plus a control. Trimmed Spearman-Karber analysis gave
      sediment 96-h LC50 values of 4.4 mumole Cu/g, 5.7 mumole Ni/g, 11.9 mumole Pb/g,
      10.3 mumole Zn/g, and pore-water 96-h LC50 values of 2 mumole/l, 11.7 mumole/l,
      and 5.7 mumole/l for Cu, Ni, and Zn, respectively. Male survival after exposure
      to Cu, Pb, and Ni was significantly less than female survival (alpha = 0.05).
      Toxicity of a combined USEPA priority metal mixture to A. tenuiremis was assessed
      using sediment spiked equitoxically with Cd, Cu, Ni, Pb, and Zn. The sum toxic
      unit that produced a median lethal dose was 0.72. The mixture had a significantly
      greater than additive effect on A. tenuiremis survival, with the mixture being
      1.4x more toxic than that expected by simple additivity.

PMID- 11468969
TI  - Effects of acid mine drainage from an abandoned copper mine, Britannia Mines,
      Howe Sound, British Columbia, Canada, on transplanted blue mussels (Mytilus
      edulis).
AB  - Juvenile mussels (Mytilus edulis) were transplanted to Howe Sound, British
      Columbia, Canada, along an apparent pollution gradient of acid mine drainage
      (AMD) from an abandoned copper (Cu) mine. Cages containing 75 mussels each were
      placed at a total of 15 stations and were exposed to concentrations of dissolved
      Cu in surface waters ranging from 5 to 1009 micrograms/l for a period of 41 days.
      Mussels located at stations closer to the source of AMD at the mouth of Britannia
      Creek bioaccumulated higher concentrations of Cu and zinc (Zn) in their tissues.
      Mussel growth was adversely affected by Cu tissue concentrations above 20
      micrograms/g dry wt., while declines in survival and condition index occurred in
      mussels that bioaccumulated greater than 40 micrograms/g dry wt. Cu. Tissue Zn
      concentrations (117-192 micrograms/g dry wt.) were likely not high enough to have
      a direct impact on mussel health. Reduced survival of transplanted mussels was
      supported by an absence of natural mussels in contaminated areas. Phytoplankton
      was also severely reduced in areas contaminated by mine waters. Based on the
      weight of evidence, AMD from the Britannia mine had a deleterious impact on
      mussel survival in a zone extending at least 2.1 km to the north and 1.7 km to
      the south of Britannia Creek on the east shore of Howe Sound.

PMID- 11468970
TI  - [The effect of cGMP on the function of immune system cells].
AB  - Cyclic GMP is a key messenger molecule in several cellular processes. It is also
      an important modulator of immune response. In this paper we summarize current
      data concerning regulatory and modulatory function of cGMP in the cells of immune
      system. Metabolism of the nucleotide as well as its role in processes such as
      cell proliferation, differentiation, chemotaxis and release of mediators are
      described. The fields of future research are indicated as well.

PMID- 11468971
TI  - [Molecular mimicry of bacterial polysaccharides and their role in etiology of
      infectious and autoimmune diseases].
AB  - Molecular mimicry is one of the most important pathogenic factor of microorganism
      and is defined as a structural similarity of microbial molecules to host tissue
      contributing to the pathogenicity. Mimicry can be observed at the molecular,
      serological and functional level. In the review the infectious diseases have been
      discussed where the mimicry phenomenon may occur, and also autoimmune disease
      where due to the molecular mimicry bacterial structures are potent to induce
      adverse immune reactions. The cross-reacting molecules mimicking the host
      structures comprise colominic acid, sialic acid containing capsular
      polysaccharides of Streptococcus group B, phosphocholine containing antigen,
      lipopolysaccharides of Campylobacter jejuni contributing in induction of Guillain
      Barre syndrome or Lewis antigen containing lipopolysaccharides of Helicobacter
      pylori inducing gut carcinoma. Knowledge on the phenomenon of molecular mimicry
      is important when new conjugate vaccine has to be constructed, because great care
      should be paid not to induce autoantibodies with synthetic immunogen.
      Investigation of microbial factors reveal that many autoimmune diseases are of
      infection etiology.

PMID- 11468972
TI  - [Polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR) and
      incidence of hyperhomocysteinemia-related diseases].
AB  - Methylenetetrahydrofolate reductase (MTHFR), is a cytosolic enzyme, the product
      of which is N5-metyltetrahydrofolate, the main form of folates in tissues and the
      carbon donor for methylation of homocysteine to methionine. In MTHFR gene a
      series of the pathogenic mutations is known which lead to loss of enzymatic
      activity as well as the two polymorphic alleles (MTHFR 677T and 1298C) with
      products displaying the lowered enzyme activity resulting in
      hyperhomocysteinaemia. These polymorphic alleles of MTHFR represent the main
      genetic factor contributing to hyperhomocysteinaemia. The better known allele
      MTHFR 677T is found in different populations with frequency between ca. 0.1 and
      0.36. In persons inheriting the variant alleles of MTHFR the increase in the
      level of homocysteine is noted resulting in the increased susceptibility to
      vascular diseases and the neural tube defects in the progeny. The procedure
      recommended for the prevention of effects of deficiency of MTHFR activity
      consists of the supplementation of the diet with 0.4 mg of folic acid daily.

PMID- 11468973
TI  - [Vascular endothelial growth factor (VEGF) and its role in neoplastic processes].
AB  - This review concerns structural and functional properties of human vascular
      endothelial growth factor as well as the process of alternative splicing of its
      transcript. Regulation of VEGF gene transcription and participation of the
      protein in the angiogenesis of tumours are also broadly discussed.

PMID- 11468974
TI  - [Characterization of DNA-protein cross-links forming under the influence of cis
      DDP].
AB  - In this article we described different nuclear proteins which have participated
      in DNA-protein cross-links induced by cis-DDP. The role of DNA-protein cross
      links in the anticancer activity of cis-DDP is discussed.

PMID- 11468975
TI  - [Selective cyclooxygenase 2 inhibitors (COX-2)].
AB  - Cyclooxygenase is key enzyme in the prostaglandin synthesis. It exists in two
      isoforms, which have distinct functions in the organism. Cyclooxygenase-2 (COX-2)
      participates in the pathophysiology of inflammation. Differences in the molecular
      structure of cyclooxygenases allowed to develop drug that selectively inhibit
      that isoform. Recently, selective inhibitors of COX-2 were introduced into
      therapy, providing new opportunities to the treatment of inflammation.

PMID- 11468976
TI  - [Activation mechanisms, biological role and inhibitors of metalloproteases in the
      extracellular matrix].
AB  - Prometalloproteinases are activated by serine proteases, MMP-3, leucocytic
      elastase, furin, furin-like proteases and by membrane-type metalloproteinases as
      well. They form complexes with some proMMPs and thus they modify their
      activation.

PMID- 11468977
TI  - [N-nitrosodimethylamine--toxicologic significance].
AB  - In this paper we have presented data on an environmental exposure to N
      nitrosodimethylamine (NDMA) and factors which favour endogenous biosynthesis of
      this compound. The factors influencing metabolism and toxicity as well as health
      effect of exposure have been reported.

PMID- 11468978
TI  - [Human aldehyde dehydrogenase (ALDH)].
AB  - The paper presents the molecular and kinetics aspects of aldehyde dehydrogenase
      polymorphism. The role in acetaldehyde metabolism and differences in substrate
      specificity of isoenzymes are discussed.

PMID- 11468979
TI  - An open letter to United Health Care.

PMID- 11468980
TI  - Do patients trust their doctors? Does it matter?

PMID- 11468981
TI  - When medical meets spiritual.

PMID- 11468982
TI  - Helicobacter pylori. A view from a primary care perspective.

PMID- 11468983
TI  - Videolaparoscopy in general surgery. An update.

PMID- 11468984
TI  - Two neurosurgeons. A bond between Nicaragua and North Carolina.

PMID- 11468985
TI  - How close is North Carolina to meeting Medicare's clinical priorities?
AB  - The analyses upon which this publication is based were performed under Contract
      No. 500-99-NC03, entitled "Utilization and Quality Control Peer Review
      Organization for the State of North Carolina," sponsored by the Health Care
      Financing Administration, Department of Health and Human Services. The content of
      this publication does not necessarily reflect the views or policies of the
      Department of Health and Human Services, nor does mention of trade names,
      commercial products, or organizations imply endorsement by the US Government. The
      authors assume full responsibility for the accuracy and completeness of the ideas
      presented. This article is a direct result of the Health Care Quality Improvement
      Program initiated by the Health Care Financing Administration, which has
      encouraged identification of quality improvement projects derived from analysis
      of patterns of care, and therefore required no special funding on the part of
      this contractor. Ideas and contributions to the author concerning experience in
      engaging with issues presented are welcomed.

PMID- 11468986
TI  - A breathless, bloated young man. Superior vena cava syndrome.

PMID- 11468987
TI  - Some reflections on the origins of biological psychiatry.

PMID- 11468988
TI  - Self perception in anorexia nervosa.

PMID- 11468989
TI  - [Harmless but subjectively dangerous. Bronchial asthma sometimes comes from the
      larynx].

PMID- 11468990
TI  - [Soon there will be potency pills for every need. What is the value of the new
      viagra competitors? (interview by Dr. Brigitte Moreano)].

PMID- 11468991
TI  - [24-hour sleep deprivation. Driving capacity of a drunk person].

PMID- 11468992
TI  - [Antibody and immunotherapy in oncology. Which patients benefit?].
AB  - Among the various immunotherapeutic approaches, monoclonal antibodies in
      particular have acquired clinical relevance. In patients with non-Hodgkin's
      lymphoma and in breast cancer it has been shown that antibody therapy and
      chemotherapy are not rival forms of treatment, but that the best clinical
      response is obtained with a combination of the two. Cellular immunotherapy with
      lymphokine-activated killer cells, tumor-infiltrating lymphocytes, allogeneic T
      cells and dendritic cells is still in the experimental stage. This is also true
      of therapeutic vaccination with tumor antigens. The best clinical results of
      treatment with antibodies or immunotherapy may be expected in patients with
      minimal residual disease.

PMID- 11468993
TI  - [Addition of hyperthermia. Heat potentiates cancer therapy].
AB  - It has been unequivocally demonstrated that hyperthermia (40-44 degrees C) has an
      potentiating effect on radiotherapy and chemotherapy. Technical improvements have
      facilitated the application of both local and whole-body hyperthermia, and have
      thus made this form of treatment available to large numbers of patients.
      Randomized phase III studies performed in patients with breast cancer, malignant
      melanoma and cervical cancer have convincingly confirmed the increased efficacy
      of the combination of radiotherapy with local or regional hyperthermia in
      comparison with radiotherapy alone. The effectiveness of other procedures such as
      the combination of radio- and chemotherapy with regional hyperthermia, regional
      thermochemotherapy and whole-body hyperthermia has so far been investigated
      mainly in phase II studies focusing on head and neck cancer, cervical and ovarian
      cancer, sarcoma, malignant germ cell tumors, and rectal carcinoma. However, the
      actual place of hyperthermia as a permanent element in a multimodal therapeutic
      concept has yet to be shown in prospective phase III studies.

PMID- 11468994
TI  - [Hope for gene therapy. Is this the future of tumor treatment?].
AB  - Conventional antineoplastic chemotherapy is limited by the low binding
      specificity of cytostatic agents and the ubiquity of critical target molecules in
      both neoplastic and normal cells. Recent advances in molecular biology have led
      to the identification of ever more genetic alterations specific to tumor cells
      that may serve as targets for gene therapy. Since appropriately designed nucleic
      acids hybridize to their "target nucleic acid" with extremely high binding
      specificity, and can be prepared with relative ease, gene therapy is
      theoretically superior to conventional chemotherapy. However, the low efficacy of
      currently available gene transfer technologies, the redundancy of genetic control
      mechanisms, and, for example under antitumor treatment, the multitude of genetic
      alterations accumulating during tumor progression represent significant problems.
      With the exception of monogenic disease, therefore, most clinical studies have so
      far demonstrated the feasibility of gene therapy, rather than its therapeutic
      efficacy. Ethical considerations rule out germline therapy. In comparison with
      conventional treatment, the assessment of the risks of this form of therapy
      should include a consideration of irreversible and reversible damage.

PMID- 11468995
TI  - [Risk of osteoporosis in steroid therapy. When and how to counter the risk].
AB  - Many chronic inflammatory diseases require treatment with steroids, however, a
      remarkable proportion of steroid-treated patients suffer from osteoporosis as a
      major complication following longterm treatment. Steroid-induced osteoporosis
      with its complex pathogenesis represents one of the most important secondary
      causes of osteoporosis. If we care for patients with steroid therapy we have both
      to consider this problem and to focus on strategies to evaluate patients at risk.
      The dosage of the steroid, life style factors, menopausal status, low bone
      mineral density at baseline and previous osteoporotic fractures predispose for
      the manifestation of steroid-induced osteoporosis. Decisions in regard of
      prevention and therapy depend on risk factors of the individual patient.
      Supplementation of calcium and vitamin D is usually appropriate, and
      postmenopausal women should be offered hormone replacement therapy. The
      prescription of bisphosphonates is strongly recommended to patients at elevated
      risk or to patients with already documented osteoporosis.

PMID- 11468996
TI  - [Acute dyspnea. It is not always the lung that whistles].

PMID- 11468997
TI  - [Secondary forms of hypertension, 3: Hypertension caused by drugs].

PMID- 11468998
TI  - [Testing of pneumococcal vaccine tolerance. For vaccine apathy there is no
      argument].

PMID- 11468999
TI  - [Safety and effectiveness fully standardized. Hexavalent vaccine can close
      vaccination gaps].

PMID- 11469000
TI  - [Insufficient and nonuniform fee reimbursement. Ups and downs of the immunizing
      physician].

PMID- 11469001
TI  - [Discussion in the forum of MMW-progress in medicine. Answers to the vaccination
      problem].

PMID- 11469002
TI  - [Cardiac arrhythmias. When is drug therapy reliable?].

PMID- 11469003
TI  - [Hypertension in type 2 diabetic patients. Calcium antagonist supports the left
      heart].

PMID- 11469004
TI  - [Study of heart failure. Is phytotherapy effective?].

PMID- 11469006
TI  - HIPAA privacy regs to impact, alter CM responsibilities.

PMID- 11469005
TI  - [Selective COX-2 inhibitor. Stomach protection--but not always].

PMID- 11469007
TI  - Trauma center boosts patient outcomes.

PMID- 11469008
TI  - Case managers improve physician involvement.

PMID- 11469009
TI  - APCs and observation: learn when to admit.

PMID- 11469010
TI  - Cutting the cost of observation: create a 'hybrid unit'.

PMID- 11469011
TI  - These aren't your usual patient ed committees.

PMID- 11469012
TI  - [Non-invasive diagnosis of coronary heart disease. Magnetic resonance tomography
      is more sensitive than CT].

PMID- 11469013
TI  - [Dangerous intoxication in diving. For whom is diving taboo? (interview by Dr.
      Beate Schumacher)].

PMID- 11469014
TI  - [Fast food, lack of exercise and insufficient treatment. Coronary heart disease
      can be prevented in 2 out of 3 cases].

PMID- 11469015
TI  - [Diagnosis of eczema. Can you recognize what your patient's symptom?].
AB  - The term eczema is applied to specific non-infectious inflammatory reactions of
      the skin, and covers a number of etiologically highly heterogeneous conditions
      which, however, demonstrate common features in terms of clinical presentation and
      pathogenesis. Eczematous disorders account for approximately 20% of the
      dermatological disturbances. They include allergic, contact and irritant contact
      dermatitis, atopic dermatitis, seborrheic dermatitis, nummular-microbial and
      dyshidrotic eczema, and stasis eczema. They have a high individual and socio
      economic impact, and are dependent on individual predisposition.

PMID- 11469016
TI  - [Dermatological local therapy. How to control eczema].
AB  - The success of a topical treatment of eczema depends not only on the active agent
      employed, but also to a large extent on the choice of a suitable base. In the
      overview, therefore, not only the physical effects of the various galenic
      preparations (solution, shaking mixture, cream, etc.) are considered, but also
      the pharmacological and clinical effects of the topical corticoids and
      alternatives, such as, for example, bufexamac, dyes, coal tar, capsaicin, as also
      radiation treatment with UV-A in combination with psoralens.

PMID- 11469017
TI  - [Allergy record. For which patient is it useful?].

PMID- 11469018
TI  - [Concepts in managing arthrosis. Experts praise old general practice drugs].

PMID- 11469019
TI  - [Which antihypertensive drugs for physically active hypertensive patients?].

PMID- 11469020
TI  - [False interpretation of laboratory results. In court it counts as a "significant
      diagnostic error"].

PMID- 11469021
TI  - [Pain when lifting arms. Anterior scalenus syndrome].

PMID- 11469022
TI  - [Disease management: chronic patients are almost favorites of national health
      insurance. Fee-for-service reimbursement not forthcoming!].

PMID- 11469023
TI  - [AIRE Study: diminished quality of life is the rule in asthma. Optimally
      controllable, still badly controlled].

PMID- 11469024
TI  - [Controlling inflammation plus bronchodilation. Advantages of fixed
      combinations].

PMID- 11469025
TI  - Soldier and family wellness across the life course: a developmental model of
      successful aging, spirituality, and health promotion, Part II.
AB  - As an alternative to the current Department of Defense approach to health
      promotion and related research, which is critiqued in Part I of this article, the
      authors present a new, integrative health promotion and wellness model. This age
      graded model incorporates successful aging, targeted health promotion, and
      spirituality in the context of the developmental perspective provided by life
      course constructs. By using an age-graded, multidisciplinary system of
      assessment, intervention, and follow-up in the context of preparing military
      personnel and families for the next season of life, this model advocates the
      prevention of disease and disability, active engagement with life, the
      maximization of high cognitive and physical functioning, and positive
      spirituality. Preliminary, selected illustrations from a variation of this model
      at the U.S. Army War College are provided. Progressive extrapolation of the model
      to other military leadership schools is proposed as a more efficacious health
      promotion strategy for the Department of Defense.

PMID- 11469026
TI  - Clinical prognosis of patients with early-stage human immunodeficiency virus
      (HIV) disease: contribution of HIV-1 RNA and T lymphocyte subset quantitation.
AB  - Systems for the staging of individuals with human immunodeficiency virus type 1
      (HIV-1) infection were developed 15 years ago. Subsequently, assays for
      quantitating HIV-1 RNA and immunophenotyping of lymphocyte subsets have been
      developed and validated. The utility of these assays for improved staging in
      early disease was evaluated in 256 HIV-infected adults (52% minority) with CD4
      counts > or = 400 cells/microL followed in U.S. military medical centers before
      the highly active anti-retroviral therapy era. HIV viral load (RNA) was
      quantitated; the frequencies of select CD4+ immunophenotypes were determined in
      112 subjects. The results were analyzed in relation to three outcome measures:
      death, first acquired immunodeficiency syndrome-defining opportunistic infection,
      and CD4 count < or = 200 cells/microL. Serum RNA level and CD4 count were each
      found to be predictive of all three outcomes. In addition, increases in the T
      cell subsets CD28-CD4+ and CD29+CD26-CD4+ were found to be independently
      predictive of more rapid progression. The classification of early-stage HIV
      patients is improved by the quantitation of both viral RNA and T-lymphocyte
      subsets.

PMID- 11469027
TI  - Henry M. Jackson Foundation for the advancement of military medicine: a brief
      history.
AB  - The Henry M. Jackson Foundation for the Advancement of Military Medicine
      (HMJFAMM) was created by Congress in 1983. This not-for-profit organization
      championed by Senator Henry M. Jackson was brought into being to serve as a
      partner with the Uniformed Services University of the Health Sciences to
      facilitate the latter's mission execution. In the foundation's 17-year history,
      which is discussed, it has served multiple functions. A major role has been to
      manage militarily relevant research. Currently, there are more than 500 research
      projects, and the HMJFAMM ranks in the top 10% of institutions receiving grants
      from the National Institutes of Health. More than 500 education funds support
      more than 200 education programs annually. Each year, hundreds of military
      physicians and research scientists are assisted in attending outside professional
      meetings. The Marion B. Sulzberger Chair, a stimulus that gave rise to the
      foundation, is among almost 50 endowments that now exist under foundation
      management. This not-for-profit institution currently employs more than 1,100
      individuals.

PMID- 11469028
TI  - History of respiratory illness at the U.S. Naval Academy.
AB  - Throughout history, respiratory diseases have been a frequent cause of morbidity
      in U.S. populations. Because of stress, crowding, and naive immune systems,
      military training populations are particularly prone to acute respiratory disease
      epidemics. An examination of the history of respiratory illness at the U.S. Naval
      Academy revealed that, in the earliest decades at the school, respiratory illness
      was a primary cause of both disease and mortality. With the advent of antibiotics
      and vaccines, most respiratory disease mortality has been reduced. However, even
      today, morbidity remains significant. Health concerns regarding respiratory
      diseases are heightened by emerging and reemerging respiratory disease agents
      that have increased antibiotic resistance and/or increased virulence. Enhanced
      surveillance and rapid diagnostic capabilities, placed in military settings, will
      increase knowledge of the epidemiology of many respiratory diseases. These
      strategies can lead to earlier treatment and prevention measures, thus halting
      the further transmission of disease and decreasing both morbidity and mortality.
      During the most recent history of the Naval Academy, acute respiratory infections
      have remained a primary cause of medical morbidity.

PMID- 11469029
TI  - U.S. Army surgical experiences during the NATO peacekeeping mission in Bosnia
      Herzegovina, 1995 to 1999: lessons learned.
AB  - Member countries of the North Atlantic Treaty Organization (NATO) initiated a
      peacekeeping mission in Bosnia-Herzegovina in December 1995. The U.S. Army has
      deployed field surgical hospitals to the region to provide ongoing medical and
      surgical care since December 1995. All surgical cases performed at U.S. Army
      field surgical hospitals in support of the NATO peacekeeping mission in Bosnia
      Herzegovina were reviewed to determine the nature of care delivered. Field
      surgical hospital operative logs served as primary data sources. U.S. Army field
      surgical hospitals were established in Bosnia-Herzegovina, Croatia, and Hungary.
      A total of 676 major operations were performed between December 1995 and
      September 1999. The mean number of operations performed per surgeon per month
      during this period was 2.13. Surgical procedures performed during this
      peacekeeping mission reflect procedures commonly performed in garrison. Other
      lessons include the need to customize field inventories for peacetime care and
      the fact that the majority of operations were general surgical or orthopedic.

PMID- 11469030
TI  - Patients above customers.

PMID- 11469031
TI  - Low-molecular-weight heparins for the prevention and treatment of venous
      thromboembolism.
AB  - Low-molecular-weight heparins (LMWHs) are rapidly becoming the anticoagulants of
      choice for the prevention and treatment of venous thromboembolism. LMWHs are at
      least as safe and effective as unfractionated heparin, and they have the added
      advantage of improved pharmacokinetic and safety profiles. The result is that
      LMWHs are easier to use, provide a more predictable anticoagulant effect, and do
      not require routine laboratory monitoring in most circumstances. Currently, the
      LMWHs ardeparin, dalteparin, danaparoid, enoxaparin, and tinzaparin have Food and
      Drug Administration-approved indications in the United States. This paper reviews
      the clinical use and cost-effectiveness of the LMWHs for the prevention and
      treatment of venous thromboembolism.

PMID- 11469032
TI  - Surgical treatment of extension contractures caused by war injuries to the knee.
AB  - Immobilization with external fixation bridging the knee joint in extension is
      frequently used after sustaining a war injury to the region of the knee joint
      with femoral and tibial bone fractures. Immobilization of the knee with plaster
      splints is performed in the same position. This usually prolonged treatment
      results in extension contractures of the knee joint. From June 1991 until March
      1994, 54 patients with extension contractures of the knee caused by war wounds
      were treated at the Department of Orthopedics, Zagreb University Hospital Center,
      in Zagreb, Croatia. Results of surgical treatment of 44 patients are presented.
      The operative procedure consisted of extensive intra- and extra-articular
      adhesiolysis of the knee. The control group included 30 patients with knee
      contractures caused by injuries sustained in car crashes or secondary to previous
      operative procedures. The mean duration of immobilization was 5 months and 6
      days. The mean preoperative knee motion amplitude ranged from 5 degrees in
      extension to 38 degrees in flexion. The mean postoperative knee motion was 98
      degrees (range, 2 to 110 degrees). Treatment results did not depend on either
      duration of preoperative immobilization of the knee or previous infection in the
      region of injury. Previous knee joint bridging with an external fixator had no
      impact on the results of extension contracture treatment. Adequate intra- and
      extra-articular adhesiolysis with appropriate long-term postoperative
      rehabilitation is essential for the success of the operative treatment for knee
      joint contracture.

PMID- 11469033
TI  - Impact of chronic low back pain on military service.
AB  - The performance of 245 male conscripts with chronic low back pain (CLBP) during
      military service was compared with their pre-conscription performance and with
      that of 126 age-matched male controls without low back pain (LBP). The frequency
      of LBP in the conscripts with CLBP increased significantly during their service
      period compared to risk before service (odds ratio, 10.35; 95% confidence
      interval, 3.61-29.52). The same factors that induced LBP before entering service,
      mainly lifting and carrying, also caused LBP during military service. Of the
      conscripts with CLBP, 120 had experienced an accidental back injury and 125 had
      injured their backs during lifting or carrying before entering service. During
      service, back problems were caused by accidents in 88 cases and by lifting or
      carrying in 157 cases. The frequency of LBP injuries, measured as the need for
      medical consultation or treatment, increased 2.4-fold (95% confidence interval,
      1.41-4.10) during the term of service. Conscripts with CLBP served significantly
      more frequently as ordinary soldiers than the controls. There was no difference
      in participation in leisure time or competitive sports activities between the two
      groups. The future expectations of the CLBP conscripts were pessimistic: only one
      fifth believed in complete recovery, and two-fifths thought that they would need
      substantial outside help in the future.

PMID- 11469034
TI  - The epidemiology of mental disorders in the U.S. Navy: the neuroses.
AB  - As part of a series of investigations into the occurrence and outcome of mental
      disorders in the U.S. Navy, this study was designed to determine first
      hospitalization incidence rates for neurotic disorders in an initially healthy
      young adult population and to determine the duration of acute illness, severity,
      and posthospital outcomes in terms of military performance and premature
      personnel losses. Data on first hospitalizations for neurotic disorders were
      extracted from automated medical record data files for all active duty Navy
      personnel admitted between 1980 and 1988. Incidence rates were calculated for
      major demographic subgroups, and career history records provided a 4-year follow
      up of service-related outcomes. Overall incidence ranged from a low of 3 per
      100,000 for obsessive-compulsive disorders to a high of 58 per 100,000 for other
      neurotic disorders/neurotic disorders not otherwise specified (NOS). The phobia
      and depressive groups had the poorest prognoses for continued service, and the
      NOS and anxiety groups had the best prognoses.

PMID- 11469035
TI  - Trauma symptomatology among female U.S. Navy recruits.
AB  - A sample of female U.S. Navy recruits (N = 1,051) was surveyed for histories of
      childhood abuse and current trauma symptomatology. Victims of only childhood
      sexual abuse (CSA) and victims of both CSA and childhood physical abuse (CPA) had
      significantly higher scores on all 10 Trauma Symptom Inventory (TSI) clinical
      scales than did participants who did not report a history of childhood abuse.
      Victims of only CPA had significantly higher scores on all TSI clinical scales,
      except the Sexual Concerns scale, than participants who did not report a
      childhood history of CPA or CSA. Additionally, more victims of childhood abuse
      positively endorsed TSI items related to suicidal behavior and ideation than did
      nonvictims. Overall, the women who experienced CPA and/or CSA reported
      substantially higher levels of trauma symptomatology.

PMID- 11469036
TI  - Tactical medicine training for SEAL mission commanders.
AB  - The Tactical Combat Casualty Care (TCCC) project initiated by the Naval Special
      Warfare Command and continued by the U.S. Special Operations Command has
      developed a new set of combat trauma care guidelines that seek to combine good
      medical care with good small-unit tactics. The principles of care recommended in
      TCCC have gained increasing acceptance throughout the Department of Defense in
      the 4 years since their publication, and increasing numbers of combat medical
      personnel and military physicians have been trained in this concept. Because
      casualty scenarios in small-unit operations typically present tactical as well as
      medical problems, however, it has become apparent that a customized version of
      this course suitable for small-unit mission commanders is a necessary addition to
      the program. This paper describes the development of a course in tactical
      medicine for SEAL mission commanders and its transition into use in the Naval
      Special Warfare community.

PMID- 11469037
TI  - Health survey reliability in an active duty population.
AB  - We examined the reliability of data collected from the Health Enrollment
      Assessment Review (HEAR) survey, a self-report instrument administered by the
      Department of Defense styled after the Behavioral Risk Factor Surveillance System
      (BRFSS). Survey responses from a convenience sample of active duty service
      members who completed a HEAR survey on two occasions were examined. We measured
      test-retest reliability by comparing individuals' responses to several of the
      survey items and compared HEAR reliability patterns with the reliability patterns
      of similar studies conducted with the BRFSS. The majority of estimates reflected
      fair to excellent reliability. We found substantial agreement between the results
      of this investigation and similar BRFSS studies. Our findings support the
      reliability of responses from the HEAR survey for active duty military members.
      Our results were generally consistent with those of other studies despite
      differences in survey administration, respondent characteristics, and privacy
      guarantees.

PMID- 11469038
TI  - Diagnostic medical auxiliary equipment in a field hospital: experience from the
      Israeli delegation to the site of the Turkish earthquake at Adapazari.
AB  - An earthquake striking a highly populated area is likely to cause a mass casualty
      situation for even the most advanced trauma center. If the local medical teams
      are injured and the hospitals are damaged beyond immediate repair, external
      intervention is needed. In the Turkish earthquake crisis, Israel was one of many
      states to deploy a field hospital to the crisis site. This was set up in
      Adapazari, the second most severely hit city in terms of the amount of damage.
      The hospital provided advanced surgical and medical facilities, including
      laparotomy, cesarean section, and intensive care surveillance. These facilities
      require sophisticated laboratory and radiology services, including hematology,
      chemistry, microbiology, and blood bank. The speed with which the hospital must
      be assembled and transported to be efficient and the basic conditions of a field
      hospital dictate specific considerations regarding diagnostic auxiliary
      equipment. Considerations in choosing this equipment, problems encountered during
      installation, and recommendations for the future are presented.

PMID- 11469039
TI  - Discharges during U.S. Army basic training: injury rates and risk factors.
AB  - This study examined injury rates and risk factors for discharge in a cohort of
      756 men and 474 women in U.S. Army basic combat training (BCT) at Fort Jackson,
      South Carolina. Investigators systematically screened trainee medical records for
      injuries and collected medical recommendations to temporarily remove a trainee
      from BCT to allow recovery from an injury. The BCT unit provided Army Physical
      Fitness Test (APFT) scores and trainee demographic data. Discharges were
      identified by reviewing discharge packets and were confirmed through rosters from
      the BCT units. There were 102 men and 108 women discharged. Person-time injury
      incidence rates (for time-loss injuries) among discharged and nondischarged men
      were 1.87 and 0.45 cases/100 person-days, respectively (p < 0.01); the rates for
      discharged and nondischarged women were 1.95 and 1.01 cases/100 person-days,
      respectively (p < 0.01). Men had a higher risk of discharge if they had a time
      loss injury (p < 0.01), but women did not (p = 0.28). Other discharge risk
      factors for both men and women included a medical recommendation for removal from
      training to recover from an injury, lower performance on any of the three APFT
      events, and lower educational level. Women with more body mass or a higher body
      mass index also had a marginally higher risk of discharge.

PMID- 11469040
TI  - A comparison of postdeployment hospitalization incidence between active duty
      Vietnam and Persian Gulf War Veterans.
AB  - Post-conflict hospitalization rates of active duty Marines deployed to the
      Persian Gulf War were compared with hospitalization rates of similar Marine Corps
      units returning from the Vietnam conflict. The aggregated Gulf War units
      exhibited lower hospitalization rates than their Vietnam counterparts. Examined
      separately, infantry and service support units deployed to the Persian Gulf had
      lower postdeployment hospitalization rates than similar units returning from
      Vietnam; no significant rate differences existed for the combat engineer and
      artillery units. The Vietnam veterans had higher percentages of hospital
      admissions for infective and parasitic diseases and genitourinary disorders than
      Gulf War veterans, whereas Gulf War veterans had a higher proportion of their
      hospitalizations in the musculoskeletal disorder category. The types of
      individual musculoskeletal disorders incurred by the two cohorts were not
      substantially different.

PMID- 11469041
TI  - Review of the Naval Health Research Center's development of medical information
      systems for far-forward echelons of care, 1983 to 1997.
AB  - Medical treatment information must be gathered quickly and accurately to ensure
      continuity of care at far-forward echelons. The manual documentation methods in
      use during the Vietnam War revealed the need for considerable improvements in
      medical information documentation, patient tracking, and effective transfer of
      data throughout each of the first three echelons of care. The U.S. military
      determined that automation would result in the greatest enhancement of
      documentation techniques. The Naval Health Research Center (NHRC) has been an
      integral part of the development of medical information systems for the Navy's
      far-forward echelons of care. The prototypes designed by NHRC for echelons I and
      II can successfully raise the standard of treatment while simultaneously reducing
      the number of individuals needed for administrative duties and increasing the
      number of medical staff available for patient care. An overview of NHRC's work in
      medical information systems from 1983 to 1997 is presented.

PMID- 11469042
TI  - Vasovagal syncope: a new treatment for an old problem.
AB  - Vasovagal syncope is an extremely common condition that is most often benign.
      However, in some individuals it can be far more severe, with frequent, sudden,
      and prolonged episodes of loss of consciousness. The effects can be traumatic,
      not only from the acute event but from the lifestyle changes that are
      necessitated by these attacks. We report on the presentation and diagnosis of
      once such individual and discuss the various treatment options. In addition,
      supported by recently published evidence, we demonstrate how a pacemaker with
      rate-drop response is an effective form of treatment.

PMID- 11469043
TI  - Patient with purely extraocular manifestations from a pit viper snakebite
      (Agkistrodon halys brevicaudus).
AB  - Snake venom can cause myriad local and systemic signs and symptoms. Neurotoxic
      effects include difficulty seeing, diplopia, difficulty in opening the mouth,
      speaking, or swallowing, and difficulty getting out of bed the morning after the
      snakebite. Because of the unique structure of the extraocular muscles, they are
      particularly susceptible to the neurotoxin. Rarely, though, are symptoms of
      snakebite confined to the extraocular muscles. This case report describes a
      patient who experienced only extraocular manifestations of envenomation. It is
      important for clinicians to recognize this unique neurotoxic manifestation and to
      begin treatment of snakebites, because delay in treatment could cause permanent
      injury and even death.

PMID- 11469044
TI  - Cost saving potential of pre-vaccination antibody testing for hepatitis B
      vaccination in military personnel.

PMID- 11469045
TI  - Clinical depression.

PMID- 11469046
TI  - [Early rehabilitation in Baden-Wurttemberg--a study of all Baden-Wurrtemberg
      early rehabilitation centers].
AB  - Over a period of 12 months, all persons among the 10.4 million inhabitants of the
      state of Baden-Wurttemberg were included in the study who had suffered severe
      brain damage and were treated in special early rehab units, comprising 147 beds
      for adults and 43 for children. With 830 patients admitted, the incidence of
      severe brain damage was 7.98/100.000 in adults and 1.11/100.000 in children. 50
      to 70 year old patients were over-represented, those older than 70 years were
      underrepresented due to geriatric rehab facilities for the latter. Male patients
      dominated, while female were somewhat younger. 54% of the patients were admitted
      from the hospital which had performed primary care, with an average stay of 67
      days. Average early rehab duration was 53 days (arithmetic average; median 40
      days, some patients required up to one year). 32.8% of the patients had suffered
      traumatic brain damage (ICD 851, 852, 854) and 40.9% non-traumatic brain
      affection (ICD 430, 431, 433-438, 310, 348), including 12.2% CVA (ICD 433-438),
      8.5% subarachnoid and 12.3% intracerebral hemorrhage. Severity as indexed by the
      early rehab Barthel index improved from an initial average of -119 to -34 at
      discharge. 80% of the patients showed an overall improvement (71% of them by up
      to 200 points and 46% by up to 100 points).

PMID- 11469047
TI  - [Socioeconomic cost-effectiveness analysis--occupational rehabilitation between
      effectiveness and social compatibility].
AB  - The fundamental question in case of planning projects of the state is which pros
      and cons are involved in their realization. Public projects take up a lot of
      social resources which hence are no longer available for other purposes-
      especially when you look at existing budgetary limits. A decision in favour of
      one specific project always implies a decision against some other project. A
      classical method to evaluate public projects is the cost-benefit analysis, which
      leads a shadowy existence owing to its difficulties in practical application
      (first and foremost in identifying and quantifying). In this article a possible
      application for cost-benefit analysis is demonstrated on the example of an
      institution for initial vocational training of young people with disabilities or
      at risk of becoming disabled. The main point here is to widen the focus from
      simply looking at fiscal expenses, revenues and savings towards also taking
      notice of social, psychological and health orientated facts. In this view it is
      very consequent to enlarge the "normal" economic balance sheet by drawing up a
      special social balance sheet which illustrates advantages and disadvantages
      difficult to measure at a monetary basis. A comprehensive decision basis is
      thereby achieved considering "both sides of the medal".

PMID- 11469048
TI  - [Pathways leading to work--the Hamburg integration specialty service].
AB  - A model project of the Federal Ministry of Labour and Social Affairs, the Hamburg
      Integrationsfachdienst zur Eingliederung Schwerbehinderter (IFD Hamburg,
      selective placement and support agency for occupational integration of persons
      with severe disablement) has been active since 1998 in placing people with
      sensory or physical handicap in the open labour market, based on cooperative
      partnership between Adecco Dienstleistungen, a market-oriented temporary staff
      business, and the vocational retraining centre Berufsforderungswerk Hamburg,
      provider of training programmes for vocational rehabilitation. The IFD combines
      social competence with business considerations (counselling employers,
      clarification of wage subsidies or grants, in-depth job analysis, preliminary
      selection of suitable job seekers). A proactive customer orientation vis-a-vis
      the prospective employer is the clear message of the IFD's consultants, which
      hence acts as a professional staff service for severely disabled job seekers in
      its dealings with the prospective customers, in their majority company decision
      makers from small and medium scale firms. Counselling and support offered to the
      disabled clients are based on a case-management approach, in partnership with the
      IFD's principals, i.e., employment office, pension insurance fund, industrial
      injuries insurance institutes, and sometimes also health insurance funds.

PMID- 11469049
TI  - [Surgical treatment and rehabilitation for improving function of shoulder muscle
      impairment].
AB  - INTRODUCTION: The results of our integrated conservative and operative concept of
      therapy to compensate insufficient shoulder muscles following brachial plexus
      palsy or other nerve damages are presented. PATIENTS/METHODS: To improve
      stability and function of the shoulder in case of deltoid and supraspinatus
      paralysis 19 patients (3 female; 16 male; average age 37 years, range 17 to 61
      years) underwent a shoulder arthrodesis. In 69 patients (12 female; 57 male;
      average age 31 years, range 19 to 69 years) a trapezius transfer was performed.
      The indication for a rotation osteotomy of the humerus to improve loss of
      external rotation due to paralytic infraspinatus muscle was determined in 5 male
      patients (average age 30 years, range 15 to 42 years). Our results are based upon
      an average follow-up of 21 (6-70) months after shoulder fusion, 21 (2-68) months
      after trapezius transfer and 28 (3-62) months after rotation osteotomy of the
      humerus. RESULTS: The trapezius transfer resulted in increased function of
      abduction of 6.6 degrees to 35.9 degrees (10 degrees-90 degrees) and forward
      flexion of 12.6 degrees to 30.9 degrees (5 degrees-85 degrees). A more stable
      condition of multidirectional shoulder instability was experienced by 64 patients
      (92.8%), and 65 patients (94.2%) were subjectively satisfied with the outcome of
      the operation. The strength and extent of functional improvement was, on average,
      greater following shoulder arthrodesis: abduction 10.3 degrees to 57.4 degrees
      (20 degrees-80 degrees), forward flexion of 12.6 degrees to 57.1 degrees (20
      degrees-105 degrees). 17 patients (89.5%) were subjectively satisfied with the
      outcome. Patients who had undergone external rotation osteotomy showed an average
      deficiency of external rotation of 30 degrees before operation. After osteotomy
      an improvement of 29 degrees to 3 degrees external rotation was achieved. All
      patients were satisfied with the increase of function. CONCLUSIONS: In patients
      with failed shoulder muscles, particularly after brachial plexus palsy, secondary
      operations according to the individual pattern of muscle failure result in an
      improvement of shoulder function and stability, as well as patients'
      satisfaction. Therefore, adequate conservative treatment before and after
      reconstructive operations is of great importance.

PMID- 11469050
TI  - [Mobility outcome after knee prosthesis implantation and subsequent physical
      therapy--factors influencing rate of success].
AB  - Osteoarthritis of the knee is considered to be the most common degenerative joint
      disease and finally ends up in a total knee replacement. Pain relief, restoration
      of a passive knee stability and improvement of functional ability are the primary
      goals of arthroplasties. But at the surgeons' closing, the patient for the
      present has just a knee "ready to function". Making the new joint function and
      recovering quality of life are the major outcome criteria for the rehabilitation
      process. This retrospective research was performed to evaluate three different
      rehabilitation programmes provided for patients receiving knee arthroplasties.
      Included were 124 patients with unilateral knee arthroplasty due to primary
      gonarthritis. All three rehabilitation clinics were able to improve the
      functional ability of the affected joints significantly, without any quantitative
      differences among them. The main influence factor in reaching the therapy aim
      (defined as: full extension and flexion > or = 90 degrees) seems to be the length
      of stay in the rehab clinic, which in turn is dependent on the presence of
      complications. On the other hand complications did not directly affect the
      achievement of the rehab goal, neither did age of patients, number of days
      between discharge (from acute care) and admission (to the rehab clinic), nor any
      accompanying illnesses. There, hence, have to be additional factors which
      influence the length of stay and so indirectly the rehab aim, factors which
      obviously are not accessible to quantitative objective measuring methods.

PMID- 11469051
TI  - [Development of a questionnaire for assessing motivational conditions for
      prediction of therapy cooperation of LVA insured patients during inpatient
      medical rehabilitation--initial results of scale development].
AB  - Medical staff working in rehabilitation often criticize their in-patients' lack
      of motivation to cooperate in therapy. Consequently, very often the aims of the
      therapy would not be reached. That, again, causes expenses that could be avoided
      and it also causes frustration on both sides. On the basis of Schwarzer's Health
      Action Process Approach (HAPA) we designed a questionnaire on motivation to
      predict the degree of the in-patients' cooperation in therapy during
      rehabilitation. The results presented here are based on an interim analysis of
      508 questionnaires answered by LVA insurees (Landesversicherungsanstalten, wage
      earners' pension insurance funds) who had applied for rehabilitation in a clinic.
      The applicants suffered from illness of the back and spine as well as
      degenerative illness of the joints. A first examination of the scales Specific
      Outcome Expectancies, Specific Self-efficacy and Intention of the questionnaire
      showed very good statistical results as well as correlations between these
      variables that correspond to HAPA. It also turned out that there is a direct
      connection between the scores of the motivation variables (e.g. Specific Self
      efficacy) and that of cooperation in therapy. These initial test results indicate
      a generic character of the instruments used in this research project. They also
      point out starting points for interventions to increase motivation that are to be
      developed.

PMID- 11469052
TI  - [Marketing orientation in rehabilitation--exemplified by image analysis of a
      rehabilitation clinic for addictions].
AB  - This article presents the findings of an image analysis carried out for a
      rehabilitation clinic for addictive diseases. The cross-sectional study was
      designed as an anonymous survey sent to relevant (regional) referral agencies (n
      = 90), e.g. counselling services for addictive diseases. The study covers the
      clinic's actual and ideal image, discriminating frequency of referrals,
      diagnostic categories, region, and type of institution. Results concerning the
      real profile indicate that on average the dimensions cooperation, communication
      with regard to personal contact, and reputation of the clinic were more
      critically judged than the issues information, communication with regard to
      discharge reports, standards of quality, and consideration of patients' needs.
      Cooperation, communication with regard to personal contact, and quality standards
      turned out to be the most important criteria from the referring agencies'
      perspective (ideal profile). A statistical comparison between those with high and
      low assignment rates suggested that customers rated the clinic more favourably
      than non-customers. Thus, it seems that the clinic's image has considerable
      influence on referral decisions. Particularly interesting is the additional
      finding that the referring institutions perceive pension insurers' directives to
      be of secondary relevance.

PMID- 11469053
TI  - ["Children with Handicaps in the Shadow of the Child Advocacy Convention"
      Symposium 27-29 October 2000 in Bonn].

PMID- 11469055
TI  - [Nose drops--therapeutic effects and applications].
AB  - Nose drops are widely used in the topical treatment of nasal disorders. This
      paper gives some aspects of the therapeutic effects and installation of nose
      drops. Nose drops are only used on the nasal mucosa. Their efficacy depend
      especially on the position of the head adopted during instillation.

PMID- 11469056
TI  - [Walter Matthias Diggelmann--the healing effect of story telling].
AB  - "Stories are weapons against disease" wrote Swiss writer WM Diggelmann (1927
      1979). In writing stories he hoped to counteract the lethal course of his cancer.
      In the past it had helped him to overcome destitution and social disgrace and had
      given him identity. His last story Walking on the Island of St. Margaret is a
      ritual which conjures up an intact future by celebrating the past. Stories try to
      explain the world. They inform or clarify emotions. In telling stories, doctors
      and nurses demonstrate sympathy and understanding. Perhaps even greater benefits
      might be derived from patients telling their own stories. In doing so they emerge
      as individuals and give their lives purpose. Language is more than communication:
      it is shelter, link, home, ritual. Storytelling helps patients cope with their
      diseases. It is not clear whether this or any technique of psychotherapy has any
      effect upon the course of cancer.

PMID- 11469057
TI  - [Hypothyroidism in chronic thyroiditis].

PMID- 11469058
TI  - [Q fever].

PMID- 11469059
TI  - [HIV-infected patient with macrohematuria. Urothelial carcinoma of the urinary
      bladder].

PMID- 11469060
TI  - Pediatric neuroanesthesia. Hydrocephalus.
AB  - Hydrocephalus, one of the most common adult and pediatric neurosurgical
      disorders, is an abnormal accumulation of cerebrospinal fluid in the ventricular
      system as a result of obstruction to the flow of cerebrospinal fluid. Causes of
      hydrocephalus include congenital obstruction, hemorrhage, infection, cysts and
      tumors, and associated neural tube deformities (i.e., myelomeningocele, Arnold
      Chiari malformation). Treatment of hydrocephalus involves surgical implantation
      of shunt systems to drain the cerebrospinal fluid. Anesthetic considerations
      involve attention to the possibility of increased intracranial pressure and
      prevention of aspiration through rapid-sequence intravenous induction and modest
      hyperventilation until the ventricles have been decompressed.

PMID- 11469061
TI  - Pediatric neuroanesthesia. Neural tube defects.
AB  - Neural tube defects of the brain and spinal cord, among the most common birth
      defects in the United States, cause neurologic morbidity from the lesions
      themselves and from associated hydrocephalus and Arnold-Chiari malformation.
      Because the myelomeningoceles, and encephaloceles are repaired surgically within
      hours of birth, neonatal anesthetic management with attention to fluids, body
      temperature, intravenous access, and monitoring is important. Anesthesia for
      treatment of hydrocephalus and Arnold-Chiari malformation takes into
      consideration the presence of intracranial hypertension and the need for
      manipulation of vital structures in the posterior fossa.

PMID- 11469062
TI  - Pediatric neuroanesthesia. Arteriovenous malformations.
AB  - Intracranial arteriovenous malformations can occur singly, multiply, and in
      conjunction with aneurysms and denovo, family, or in conjunction with connective
      tissue disorders. Intracranial hemorrhage is the most common presentation,
      occurring in 20% to 50% of cases. In children, seizures are the second most
      common presentation occurring in 15% to 20% of cases. The modalities available
      treatment of arteriovenous malformations are microsurgery, embolization, and
      stereotactic radiosurgery with heavy particles, alpha knife, or linear
      accelerator. Induction, maintenance, and emergence from anesthesia are designed
      to prevent rupture of arteriovenous malformation and aneurysm and to improve
      intracranial compliance in the presence of an intracranial hematoma, during both
      diagnostic (CT, MR scanning) and therapeutic procedures.

PMID- 11469063
TI  - Pediatric otolaryngologic emergencies.
AB  - Anesthesiologists are often consulted to help in the management of pediatric
      otolaryngologic emergencies. These include airway obstruction in children
      suffering from acute epiglottitis and croup. Surgical otolaryngologic emergencies
      such as foreign body aspiration, post-tonsillectomy bleeding, obstructive
      laryngeal papillomatosis, peritonsillar abscess, and laryngeal trauma can be life
      threatening. The pathophysiology, clinical course, and anesthetic management of
      these conditions are addressed with special emphasis on the details of airway
      management in each case.

PMID- 11469064
TI  - Pediatric eye emergencies.
AB  - Anesthesia for pediatric eye emergencies is predicted on prevention of a rise in
      intraocular pressure and avoidance of extrusion of the intraocular contents in
      the setting of a full stomach. Sedation or general anesthesia is frequently
      necessary for adequate examination of the eye.

PMID- 11469065
TI  - Neonatal surgical emergencies.
AB  - Improvements in the diagnosis and treatment of congenital disorders have resulted
      in a change in surgical practice. Many conditions that formerly required
      corrective surgery immediately after birth are no longer surgical emergencies.
      Most babies with congenital anomalies that can be corrected by surgery are now
      stabilized and optimized before the procedure. This article focused on the more
      common conditions that require semi-elective or urgent surgery in the neonatal
      period. Salient features of each of these disorders were described. Factors
      unique to each of these conditions that can affect the anesthetic course of these
      children were discussed. Methods and techniques that may aid in the anesthetic
      management of these children were delineated.

PMID- 11469066
TI  - Pediatric cardiac emergencies.
AB  - Successful management of pediatric cardiac emergencies requires an accurate
      diagnosis to institute an appropriate plan of therapy. The diagnosis, however, is
      not always straightforward, as evidenced by the nonspecific clinical picture that
      can be presented by congenital heart defects. Entertaining the possibility of a
      cardiac problem in neonates with pulmonary symptoms unresponsive to standard
      therapies is crucial for successful management of patients with congenital heart
      disease. In addition to ventilatory support, prostaglandin E1 infusions or
      emergency interventional cardiac catheterization is often a life-saving initial
      measure in patients with acutely decompensated congenital cardiac lesions that
      require a patent ductus arteriosus for survival. Pericardial tamponade is
      associated with various acquired and iatrogenic causes. Emergent
      pericardiocentesis is mandatory when cardiovascular compromise occurs. The goal
      of anesthetic management is to maintain cardiac output. With the increasing use
      of central venous catheters in neonatal ICUs and the high mortality rate for
      central venous catheter-related cardiac tamponade, the diagnosis must be
      considered in any patient with a central venous catheter in situ who acutely
      develops unexplained hypotension, bradycardia, and diminished pulses. Arrhythmias
      also can cause hemodynamic instability in infants and children. Supraventricular
      tachycardia is by far the most common emergently presenting arrhythmia in the
      pediatric population. Unstable patients require immediate intravenous adenosine
      or synchronized cardioversion. Complete heart block is rare, but it can lead to
      congestive heart failure and occasionally to cardiovascular collapse and sudden
      death. Emergency treatment of complete heart block includes pharmacologic support
      and temporary or permanent pacemaker placement as indicated. In infants,
      congestive heart failure usually is related to congenital heart disease, whereas
      in older children, it tends to be secondary to an acquired cause. Supportive
      measures, fluid restriction, and inotropic support are the principles of initial
      treatment. Prompt recognition and initiation of appropriate therapy in pediatric
      cardiac emergencies are essential for favorable outcomes.

PMID- 11469067
TI  - Pediatric trauma. Anesthesia management.
AB  - Prevention of childhood injury remains the cornerstone of reducing the number of
      children who present for post-traumatic surgical intervention. Beyond prevention,
      the next best step is the accurate diagnosis and treatment of traumatic injury.
      Anesthesiologists contribute to this step by providing timely resuscitation and
      optimal care to avoid secondary injury. This article classifies trauma in
      children into different categories depending on the location of the injury.
      Trauma, of course, is rarely focal, and is often a multisystem entity. With
      knowledge in management for each subset of trauma, one may be efficient in
      prioritizing injury and have a good understanding of the appropriate management
      of the pediatric patient with multiple traumatic injuries.

PMID- 11469068
TI  - Pediatric resuscitation in the operating room.
AB  - The resuscitation of pediatric patients undergoing anesthesia involves
      appropriate administration of fluid and blood products and stabilization of vital
      signs. Crystalloid is first-line therapy for fluid resuscitation, and should be
      given with awareness of its potential dilution of the child's hematocrit. Many
      alternatives to homologous blood transfusions now exist, however, when necessary
      for increasing oxygen-carrying capacity or treating coagulopathy benefits likely
      outweight the risks. The risks for such transfusion include infectious,
      hemolytic, metabolic, and immunologic effects. When fluid and blood
      administration does not stabilize the patient, the differential diagnosis of
      hypotension, arrest, or arrhythmias must include medication errors, anesthetic
      overdose, electrolyte disturbances, hypoxemia, ventilatory problems, and surgical
      insults, including medications given in the operative field. Resuscitation should
      include treatment of hypocalcemia and hyperkalemia, chest compressions, and the
      administration of epinephrine when necessary.

PMID- 11469069
TI  - General pediatric emergencies. Malignant hyperthermia syndrome.
AB  - Anesthesiologists always undertake the challenge of keeping themselves informed
      about advances in medical knowledge aggressively; however, they have not been
      particularly active in the areas of patient education and advocacy. Malignant
      hyperthermia syndrome is a unique condition that anesthesiologists as clinicians
      understand well--in most cases, better than other specialists. They are
      positioned best to inform patients initially about the significance of malignant
      hyperthermia syndrome susceptibility and to provide an ongoing resource for
      counseling. The physician-patient relationship, according to the American Society
      of Anesthesiologists' Guidelines for the Ethical Practice of Anesthesiology,
      "involves special obligations for the physician that include placing the
      patient's interest foremost, faithfully caring for the patient, and being
      truthful." The care, counseling, and support that anesthesiologists bring to the
      patient susceptible to malignant hyperthermia syndrome truly fulfills this
      relationship.

PMID- 11469070
TI  - General pediatric emergencies. Acute pulmonary edema.
AB  - This article focuses on three types of acute pulmonary edema in children:
      negative-pressure pulmonary edema, neurogenic pulmonary edema, and cardiogenic
      pulmonary edema.

PMID- 11469071
TI  - Pediatric resuscitation outside the operating room.
AB  - Protocols regarding the treatment of cardiac arrest of the pediatric patient
      outside the operating room are continually being reviewed as knowledge regarding
      the pathophysiology of cardiac arrest and the pharmacologic properties of
      resuscitative drugs has progressed. The indications for treatment of cardiac
      arrest by the various resuscitative drugs, and techniques for obtaining access
      for the administration of these drugs are discussed.

PMID- 11469072
TI  - Pediatric ventilation outside the operating room.
AB  - Various ventilatory techniques have been developed in recent years to treat
      severe respiratory disease states in the pediatric population. Techniques and
      strategies involving the use of conventional ventilation, high frequency
      ventilation, nitric oxide, partial liquid ventilation, and extracorporeal
      circulation are discussed.

PMID- 11469074
TI  - Repetitive mucosal trauma promotes colon cancer in experimental rat model.
AB  - OBJECTIVE: To investigate the effect of repetitive mucosal trauma, anastomosis
      and intestinal content on experimental colonic carcinogenesis as there is the
      possibility than non-specific colon lesions can promote cancer. MATERIAL AND
      METHOD: We performed to sixty female Sprague-Dawley rats a 4 cm colon loop
      defunctionalization with double colostomy (traumatic site). Intestinal continuity
      was restored with an end-to-end colo-colic silk anastomosis. The surviving 47
      rats were divided in 3 groups: Group A: 27 rats treated with DMH. Group B: 10
      rats treated with EDTA and Group C: Control of 10 rats. Animals were sacrificed
      31-32 weeks after surgery for macro and micropathological studies. RESULTS: In
      group A appeared 60 tumours: 44 in the functional colon, 20 of them in the
      anastomotic site; 8 in the non traumatised defunctionalized segment and 18 in the
      traumatised segment (p < 0.05). CONCLUSIONS: a) Continuous microtraumas on
      colonic mucosa in rats are cancer promotional factors; b) silk suture in
      anastomosis promotes cancer.

PMID- 11469075
TI  - Growth hormone and nutrition as protective agents against methotrexate induced
      enteritis.
AB  - OBJECTIVE: To determine whether exogenously administered growth hormone can
      reduce or prevent chemotherapy-induced intestinal mucosa injury. The expected
      results will allow to consider its potential clinical use. DESIGN: Experimental
      and randomized study. SETTING: Experimental Surgery Service, La Paz University
      Hospital. SUBJECTS: Adult Wistar rats weighing 250-300 g. MATERIALS AND METHODS:
      A chemotherapy protocol with methotrexate (MTX) (120 mg/kg) was employed. Animals
      fed either with a normoproteic or a hyperproteic liquid diet were treated with
      either saline or growth hormone (1 mg/kg/day) since three days before until four
      days after chemotherapy. Animals were sacrificed seven days after MTX
      administration for tissue sampling. RESULTS: Co-administration of growth hormone
      and a hyperproteic diet increased intestinal crypt proliferation and reduced MTX
      induced apoptosis. CONCLUSIONS: Jejunal mucosal structure (morphometry),
      proliferation (Ki-67) and apoptosis (TUNNEL) were assessed.

PMID- 11469076
TI  - C282Y and H63D mutations of HFE gene in patients with advanced alcoholic liver
      disease.
AB  - OBJECTIVE: To test the hypothesis that the heterozygous state for HFE gene
      mutations involved in the pathogenesis of hemochromatosis, that may induce an
      increase of hepatic iron content, may aggravate the liver damage induced by
      prolonged and excessive use of ethanol. PATIENTS AND METHODS: C282Y and H63D
      mutations of HFE gene were identified through polymerase chain reaction (PCR) on
      leukocyte DNA, in 125 consecutive patients diagnosed of advanced alcoholic liver
      disease (109 men, mean age 54 years, SD 11) and 181 healthy controls. All
      subjects were white Spaniards. RESULTS (CASES/CONTROLS): 1. Genotype
      distribution: a) mutation C282Y: no homozygotes, 10/23 heterozygotes, 115/158
      normal (p = 0.60); b) mutation H63D: 9/5 homozygotes, 46/52 heterozygotes, 70/124
      normal (Chi square 6.51, p = 0.039). 2. Allele frequencies: a) mutation C282Y:
      240/339 normal, 10/23 mutated (p = 0.21); b) mutation H63D: 186/300 normal, 64/62
      mutated (odds ratio 1.66, 95% CI 1.10-2.52, p = 0.01). CONCLUSIONS: Our results
      suggest that H63D mutation of the HFE gene, but not the C282Y mutation, is
      associated to the risk of developing advanced liver alcoholic disease.

PMID- 11469077
TI  - Validation of the Spanish version of the Glasgow Dyspepsia Severity Score.
AB  - OBJECTIVE: To translate, adapt and validate the Spanish version of the Glasgow
      Dyspepsia Severity Score (GDSS). METHOD: The translation into Spanish and the
      adaptation of the scale was carried out by specialized medical translators. The
      comprehensibility of the translated scale was assessed by two independent
      observers and by the research team. GDSS includes eight items and was filled out
      once by 40 healthy subjects (control group) and twice by 131 patients with
      functional dyspepsia. After the first measurement, patients were prescribed a H2
      blocker (roxatidine) for 2 months. A second evaluation was carried out 6 months
      after the beginning of the treatment. RESULTS: The comprehensibility of the
      questionnaire was good. It showed acceptable internal consistency both for the
      control group (0.6) and for the patients at the inclusion visit (0.6) and good
      consistency for the patients at the 6 month follow-up evaluation (0.8). After
      treatment, the overall score decreased almost to half (p < 0.0001) in the
      patients, thus confirming the effectiveness of the treatment 4 months after its
      discontinuation, although their score was still higher than the score of the
      control group (p < 0.001). CONCLUSIONS: Results suggest the usefulness of
      including the GDSS scale in the dyspeptic symptoms recording protocols, since it
      allow to estimate, with appropriate objectivity and in an easy and quickly way,
      the degree of impairment due to dyspeptic symptoms, as well as the perception of
      well-being and the effectiveness of a given therapy.

PMID- 11469078
TI  - Miserere colic (Miserere mei). Contribution on etymology and clinical features;
      hypothesis on its appearance in medical literature during centuries 17th-18th.
AB  - The definition of ileus has undergone deep changes over the last three millennia.
      The term ileus was originally used in Classic Greece to describe a common cause
      of intestinal obstruction, and subsequently the Romans would often translate it
      into the Latin word volvulus. During the Renaissance, ileus, volvulus and
      intussusception became synonymous with a vulgar term--Miserere Mei or Miserere
      colic--whose origin and evolution are still much of a mystery. This paper
      provides some historical investigation on the Miserere Mei or Miserere colic,
      with the aim of discussing its evolution within medical literature during the
      17th and 18th centuries.

PMID- 11469079
TI  - [Surgical treatment of gastrointestinal stromal tumor].

PMID- 11469080
TI  - [Co-existence of MALT tumor, Helicobacter pylori and HIV].

PMID- 11469081
TI  - [Toxic hepatitis due from amoxicillin-clavulanic acid].

PMID- 11469082
TI  - [Medical treatment of sclerosing mesenteritis secondary to abdominal surgery].

PMID- 11469084
TI  - [Hemorrhoidectomy].

PMID- 11469083
TI  - [Adenocarcinoid of the appendix: prognostic factors and current treatment].

PMID- 11469085
TI  - [Pathophysiology of hemorrhoids].
AB  - It is not easy to define haemorrhoidal complaints precisely since this
      automatically means the entire aetiology and pathogenesis. What Stelzner
      describes as a complex compound of arteriovenous links in the rectal mucosa with
      an interlace of unstriated muscles, elastic fibres and connective tissue forms
      the anatomic base of the "corpus cavernosum recti". This cavernous vascular
      padding is a crucial component of the continence organ and ensures a gas-tight
      seal. According to Thomson's studies, haemorrhoids are to be regarded as a
      consequence of the disintegration of muscular and elastic components, caused by a
      distal shift of the vascular padding. The changes can cause growth up to
      prolapse, as well as haemorrhage or congestion. The reasons have not yet been
      conclusively clarified. Malfunctioning intestines--in particular constipational
      changes with hard stool--seem to be causal factors. The mechanisms of function
      and control of arteriovenous links as well as the influence of hereditary, social
      and cultural disposition continue to be unclear.

PMID- 11469086
TI  - [Hemorrhoids. On the evaluation of different surgical procedures].
AB  - The spectrum of procedures for haemorrhoidal disease can deal with all
      developmental stages if done in a differentiated way. The possibilities,
      limitations, and risks of the different methods are described. The catalogue
      stretches from relatively simple operations (Milligan-Morgan, stapler
      haemorrhoidectomy), which every general surgeon should be able to perform, to
      extensive anoplastic reconstruction, which is limited to specialists. Although
      the global risks of the more simple operations make them suitable for outpatient
      procedures, there are--at least in Germany--severe reservations, as there is the
      danger of inadequately therapy in more advanced cases, overcharging a lot of
      patients, lack of cooperation and knowledge about the necessities of early
      postoperative care by the local practitioners, problems in follow-up in patients
      living far away, and inadequate payment for the therapeutical costs by the health
      insurance companies.

PMID- 11469087
TI  - [Ambulatory hemorrhoid therapy].
AB  - For thousands of years, anal complaints were treated symptomatically with
      ointments, suppositories and, in isolated cases, even surgically. Since the
      middle of the last century injection sclerotherapy has been by far the most
      widespread out-patient treatment for the very common haemorrhoidal disease. This
      is based on the notion that haemorrhoids are varicosities, and while this idea
      has been contested by the theory of a spongy body for over 200 years, it is
      nonetheless only in the last 40 years that the spongy body theory has become
      accepted, giving rise to further important functional investigations on the anal
      structures involved in bowel continence and to rational treatment for
      haemorrhoids. The conditions necessary for out-patient treatment of haemorrhoids
      and the options available are presented in this paper and discussed with
      reference to acceptance, inherent risks, and the possible complications. While
      diet and behavioural methods, and also anal dilatation and treatment with
      ointments, can be managed by the patient without any problems, regardless of how
      effective sclerotherapy and rubber band ligation are, these involve risks whose
      ramifications are often underestimated. One operative procedure that may well
      become established as an effective out-patient method in the future is Doppler
      guided isolated haemorrhoidal artery ligation (HAL) after Morinaga.
      Traditionally, day surgery is not so well accepted for haemorrhoidectomy in
      Germany; unless the operation planned is not very extensive, in-patient treatment
      is still considered preferable.

PMID- 11469088
TI  - [Therapy of traumatic anterior shoulder dislocation: current status of therapy in
      Germany. Are there scientifically verified therapy concepts?].
AB  - There are no generally accepted concepts for the treatment of traumatic anterior
      shoulder dislocation. The objective of this study was to ascertain the current
      treatment for traumatic shoulder dislocations in German hospitals and to compare
      this with the data reported in the literature. A total of 210 orthopedic surgery
      departments were asked for their treatment strategy in an anonymous country-wide
      survey; 103 questionnaires (49%) were returned for evaluation. Additional imaging
      (ultrasound, CT, MRI) beyond the routine X-rays is performed in 82% of clinics
      for primary shoulder dislocation (94% in recurrent dislocation). A young,
      athletic patient (< 30 years old) would be operated on for a primary traumatic
      shoulder dislocation in 73% of hospitals (98% in recurrent dislocation). In
      contrast, a patient of the same age, with a moderate level of sporting activity
      would be treated conservatively in 67% of cases (14% in recurrent dislocation).
      Similarly, for an active, middle-aged patient with a demanding job, 74% of
      responses favored conservative treatment after a primary dislocation and 6% after
      a recurrent dislocation. Older patients (> 65 years old) are usually treated
      conservatively after a primary or recurrent shoulder dislocation (99%, 69%). For
      a primary shoulder dislocation the most popular surgical reconstruction is a
      Bankart repair (75%). For recurrent shoulder dislocation several different
      operative techniques are seen (Bankart 29%, T-shift 26%, Putti-Platt 8%, Eden
      Lange-Hybbinette 22%, Weber osteotomy 13%). Based on our literature review, we
      found: (1) The clinical examination of both shoulders is important to diagnose
      hyperlaxity; (2) Routine CT or MRI is not necessary for primary traumatic
      shoulder dislocations; (3) A young, athletic patient should undergo surgical
      reconstruction after a primary shoulder dislocation; (4) The operation of choice
      for primary and recurrent dislocation is the Bankart repair; (5) There is no
      sufficient evidence that an arthroscopic Bankart repair is as good as an open
      procedure; (6) There are limited indications for other operative techniques, as
      they are associated with a higher recurrence and arthrosis rate.

PMID- 11469089
TI  - [Neurogenic appendicopathy: a frequent, almost unknown disease picture.
      Evaluation of 816 appendices and review of the literature].
AB  - BACKGROUND: Neurogenic appendicopathy (NA) represents an almost unknown pathology
      which clinically cannot be differentiated from acute appendicitis. The diagnosis
      can only be established histologically. Nerve proliferation and an increased
      number of endocrine cells are typical for NA. This study characterizes the
      epidemiology, histology, clinical appearance and therapy of NA. We evaluated the
      incidence of NA in macroscopically normal specimens from patients presenting the
      symptoms of acute appendicitis and in incidental appendectomies. PATIENTS AND
      METHODS: 816 routine appendix specimens were examined at the Institute of
      Pathology, University of Basel, for the presence of NA. We analyzed the
      indication for appendectomy, the histological form and the age and sex of the
      patients. RESULTS: 140 appendices (17.1%) showed the histological criteria for
      NA. 25% of incidental appendectomies were positive for NA, as opposed to 53% of
      the macroscopically normal specimens of patients presenting the symptoms of acute
      appendicitis (P < 0.0001). NA is more frequent in men than in women (19.5% versus
      14.5%, P = 0.057). Out of the total of 140 NA, 105 (12.9%) were classified as
      central, 12 (1.5%) as intramucosal and 5 (0.6%) as submucosal forms of NA. 18
      times (2.2%) the histologic subtype of NA was not specified. CONCLUSIONS: This
      study establishes that NA is a frequent, often asymptomatic pathology. In more
      than half of the macroscopically normal specimens of patients presenting symptoms
      of acute appendicitis NA can be diagnosed, significantly more than in incidental
      appendectomies. Therefore it is imperative to remove and analyze a
      macroscopically normal appendix in a patient presenting symptoms of acute
      appendicitis if no other intraabdominal pathology can be found.

PMID- 11469090
TI  - [Surgical treatment of cicatricial carcinoma--methods and results].
AB  - INTRODUCTION: The prognosis of scar carcinoma, also known as Marjolin's ulcer, is
      poor. Metastases of lymph nodes often appear because of late diagnosis and the
      underestimation of clinical findings. This has a deep impact on the quality of
      life of the patients. Scar carcinoma often occurs in burn scars, but also in
      chronic ulcers of the lower extremities and in chronic pressure sores. METHODS:
      Between 1994 and 1998 12 patients with scar carcinoma were treated at our
      hospital. In all cases radical surgery of the entire scar area was undertaken,
      followed by dissection of the draining lymph nodes. Free flaps, pendicular flaps
      or splint skin grafts were used to cover the resulting defects. RESULTS: In 16.6%
      we observed positive lymph nodes. There were two cases of local recurrence. Five
      patients died during the observation time. In one patient the extremity had to be
      amputated. CONCLUSION: Early diagnosis and radical excision are requirements, and
      the quality of life can be improved with plastic surgery. Aftercare and yearly
      staging measures are mandatory.

PMID- 11469091
TI  - [Ultrafast magnetic resonance tomography changes the standard in pancreas
      diagnosis].
AB  - BACKGROUND: Since the introduction of MRI, including imaging of the hepato
      pancreatic duct system (MRCP) and 3D-MR angiography (3D-MRA), new pancreatic
      diagnostic procedures have been developed. METHODS AND PATIENTS: We report on 143
      patients with benign and malignant diseases of the pancreas, who only received
      MRI preoperatively. All radiologic findings were confirmed intraoperatively.
      RESULTS: For resectability, MRI obtained sensitivity of 96.0% and specificity of
      89.5% and for classification sensitivity of 99.1% and specificity of 95.2%.
      CONCLUSION: Based on our experience, the benign vs malignant nature of the
      disease, MRI is a safe and reliable method for pancreatic tumors being able to
      become the standard diagnostic procedure in the future.

PMID- 11469092
TI  - [Surgical palliation of pancreatic carcinoma. Results of a 7 year period].
AB  - INTRODUCTION: High perioperative complication rates in the 1980s led to preferred
      use of endoscopic therapy for surgical palliation of pancreatic cancer. This
      encouraged us to analyse our own patients retrospectively. MATERIAL AND METHODS:
      In the period from 1 January 1992 to 31 December 1998, 253 patients with an
      exocrine carcinoma of the pancreas were operated on at the St. Elisabeth Hospital
      Cologne-Hohenlind: 73 patients (28.9%) underwent curative resection (R0) while
      180 patients (71.1%) had palliative operative treatment (R1/R2). Palliative
      resection was performed in 22 patients (8.7%). Intestinal bypass surgery was done
      in 113 patients (44.7%) as a gastrojejunostomy and in 16 patients (6.3%) as a
      duodenojejunostomy. A biliodigestive anastomosis was performed in 85 patients
      (33.6%). This procedure was combined with a gastroenterostomy in 78 patients
      (30.8%). In 18 patients (7.1%) no surgical palliation was possible and the
      operation finished as a diagnostic laparotomy. RESULTS: The overall mortality
      rate within the first 30 (60) days was 5.5% (12.7%). Patients whose carcinoma had
      been resected curatively had a 30 (60)-day mortality rate of 2.7% (4.1%),
      compared to a rate in palliatively treated patients (resection/bypass/probatoria)
      of 6.7% (16.1%). Patients with palliatively resected tumor had perioperative
      mortality of 4.5% (4.5%), whereas patients who did not undergo resection had 6.9%
      (17.7%). The survival rate for curatively resected patients after Kaplan-Meier
      extrapolation was 64.7% after 1 year and 31.2% and 26.2% after 3 and 5 years,
      with a median survival time of 552 days. Palliatively operated patients had a
      survival rate of 19.4%, 2.5% and 0% for 1, 3 and 5 years. Median survival time
      was 171 days in this situation. Compared to patients without resection (17.4% and
      2.0%), patients with palliative resection had survival rates for 1 and 3 years of
      40% und 5.9%. After 5 years none of these patients were alive. CONCLUSIONS: Our
      data show a high success of surgical palliation in pancreatic cancer in centers
      with a high frequency of pancreatic surgery. Patients that could not be cured
      (R1/R2), although undergoing extensive procedures, had better survival rates than
      patients treated with bypass surgery. Perioperative mortality rate was
      comparatively low. This justifies aggressive surgical management of pancreatic
      carcinoma.

PMID- 11469093
TI  - [Thromboembolism complication in multiple trauma patients: an underestimated
      problem? Results of a clinical observational study of 50 patients].
AB  - INTRODUCTION: The incidence of thromboembolic complications in patients with
      severe polytrauma in the ICU is not well known. Only a few publications deal with
      this problem. Systematic investigations in this high-risk patient group are not
      routinely used. METHOD: From January 1996 to January 1998, 50 polytrauma patients
      with a mean ISS > 15 were included in a clinical study to evaluate the incidence
      of thromboembolism in this patient group. Further inclusion criteria were a
      minimum stay of 72 h in the ICU and mechanical ventilation for a minimum time of
      72 h. All patients were examined with color-coded duplex sonography according to
      a standardized protocol. The duplex sonography was performed before the patients
      were first mobilized in the ICU (15 +/- 12.8 days). RESULTS: If not otherwise
      indicated all values are given as mean +/- SD. The age of the patients was 38
      years (range 17-77 years), the severity of trauma was characterized by an ISS of
      40 (range 16-70). Eight of the included patients died during their stay in the
      ICU after developing a multiple organ failure. According to autopsy data none of
      them had a deep venous thrombosis or pulmonary embolus. Eight patients (19%)
      developed deep venous thrombosis, and 4 patients with thrombosis developed
      pulmonary embolism. CONCLUSION: The incidence of deep venous thrombosis in
      polytrauma patients seems to be much higher than expected reviewing the results
      of other publications. The low detection rate of other authors results from using
      only clinical signs. The routine use of color-coded duplex sonography is
      effective in detecting unsuspected deep vein thrombosis.

PMID- 11469094
TI  - [Experiences with using a potentially temporary vena cava filter in multiple
      trauma patients].
AB  - INTRODUCTION: In Europe, there is little experience in the application of
      temporary cava filters in patients with multiple injuries. Especially patients
      with pelvic injuries, fractures of the spine, and the lower extremities are at
      high risk for thromboembolic events like thrombosis or pulmonary emboli.
      Moreover, in patients with severe head injuries, anticoagulation is
      contraindicated. METHOD: We present in this paper our experience with 24
      consecutive patients with multiple injuries who were treated with a temporary
      cava filter. The insertion site was either the femoral (n = 20) or the jugular (n
      = 4) vein. The 24 patients revealed a mean ISS of 35.1 +/- 2.01 points. Nineteen
      patients had pelvic injuries and 17 patients suffered from severe head injury. In
      17 patients the insertion of the filter was prophylactic, in 4 patients a
      thrombosis was present and in 3 patients a non-fatal pulmonary emboli was
      diagnosed before the application of a cava filter. RESULTS: No complication
      occurred due to insertion of the filter. In one patient a thrombosis of the cava
      was observed as the only overall complication (1 of 24 = 4.2%). CONCLUSION: The
      insertion of a cava filter in patients with multiple injuries with
      contraindication for anticoagulation is a safe and effective procedure to prevent
      fatal pulmonary emboli.

PMID- 11469095
TI  - [Scoring multiple organ failure after severe trauma. Comparison of the Goris,
      Marshall and Moore scores].
AB  - INTRODUCTION: MOF scores are used to predict, describe and define organ failure.
      The aim of this study was to compare MOF scoring systems regarding their
      precision. METHODS: Data on the ICU course of 301 severely injured patients (PTS
      > 20, age > 16 years) were documented daily for calculation of three MOF Scores
      (Goris, Moore, Marshall) for 14 days. Every day the patients were graded by
      clinical criteria into a group with and a group without MOF by an experienced
      intensive care physician. The cut-off point for MOF was determined by ROC
      analysis for each score; the sensitivity and specificity were calculated.
      RESULTS: The patients were 36.3 +/- 1.0 years old, the mean injury severity was
      36.2 +/- 0.7 points according to the PTS. Forty-seven (15.6%) of all patients
      died 17.7 +/- 5.6 days after trauma. The MOF incidence was 26.1%, the MOF
      mortality 58.4%. The calculated cut-off point for MOF was more than 4 points for
      the Goris and Marshall scores and more than 3 points for the Moore score. The
      Moore score is, with sensitivity of 81% and specificity of 88%, superior to the
      other scores. The Moore score identified 93 patients (30.9%) for MOF; this
      corresponds with a right answer in 85%. The lower specificity of the Goris and
      Marshall scores was due to the judgement of liver (GOT) and cardiovascular (PAH)
      dysfunction respectively. CONCLUSION: For evaluation of MOF after severe trauma
      the Moore score is superior to other scoring systems (sensitivity 81%;
      specificity 87%). A score of more than 3 points is associated with MOF. The Moore
      score did not consider distinct parameters (S-GOT, PAH) which are included in the
      other systems and were of little importance in our calculations.

PMID- 11469096
TI  - [Intraoperative radiotherapy--progress with a CT-assisted navigation system].
AB  - INTRODUCTION: The fact that conventional intraoperative radiotherapy (IORT) does
      not give the opportunity for exact documentation of the applied radiation volume
      and dose distribution has been criticised. We would like to introduce a system
      for surgical navigation and documentation of the flab positioning for
      intraoperative brachytherapy in afterloading flab technique. METHODS: Our system
      consists of an electromagnetic 3D digitizer and a PC workstation. Preoperatively
      taken spiral CT scans of the tumour region are used for navigation and
      documentation of the flab positioning, analogous to the procedure in
      neuronavigation. Registration is done via an external reference system attached
      to the iliac bone of the patient. RESULTS: The mean accuracy of digitalization of
      the 100 spheres in a pelvis model is about 2.6 +/- 0.5-3.7 +/- 0.9 mm. Mean
      navigation accuracy is 2.4 +/- 0.8-3.3 +/- 0.8 mm. These figures correspond to
      the clinical experience of our surgeons. CONCLUSIONS: The optimization of the
      flab positioning by CT-guided navigation and the more accurate documentation of
      the dose volume and distribution in the patient is an important step towards
      improving the quality of individual radiotherapy. We are of the opinion that
      surgical navigation in the pelvic region should be subject to additional
      investigation in order to optimize the procedure.

PMID- 11469097
TI  - [Life threatening complication after transthoracic esophageal resection].
AB  - Acute inflow stasis of the vena cava superior is an emergency case. Because of
      the rapidly rising venous pressure, life-threatening complications can arise
      (e.g. cerebral hemorrhage, hemorrhagic venous infarcts). The main cause of
      central venous thrombosis is bronchial carcinoma (incidence: 3-5%). Iatrogenic
      reasons are thrombosis caused by pacemaker electrodes, dialysis catheter, central
      vein catheters, implanted ports and radiation-induced venous fibrosis. In this
      case a patient with an esophageal carcinoma was pretreated by a neoadjuvant
      chemoradiotherapy. The chemotherapy was given through a venous access port, which
      was implanted earlier. Radiation therapy with a total of 60 Gy followed. After
      the esophagectomy the patient developed an acute inflow stasis of the vena cava
      superior.

PMID- 11469098
TI  - [Tuberculosis of the pancreas--a clinical rarity].
AB  - Pancreas tuberculosis is a rare diagnosis and is usually associated with miliary
      spread. Only a few cases are reported in the literature. A female patient was
      admitted with a history of uncharacteristic abdominal pain, weight loss,
      weakness, and intermittent fever. CA 19-9 was increased and the CT scan showed an
      irregular mass in the pancreatic tail. Suspecting the diagnosis of pancreatic
      cancer, a pancreas tail resection with splenectomy was performed. The
      histological examination showed pancreas tuberculosis. Mimicking pancreatic
      cancer or presenting with acute/chronic pancreatitis or obstructive jaundice, the
      diagnosis of pancreas tuberculosis is very difficult to make and is usually
      established after surgical treatment. Although pancreas tuberculosis is rare, it
      should be considered when evaluating a pancreatic mass.

PMID- 11469099
TI  - [Idiopathic sclerosing mesenteritis. Case report and differential diagnosis of a
      rare disease picture].
AB  - We report the case of a 78-year-old woman with the endoscopic tentative diagnosis
      of a malignant tumor of the colon ascendens (biopsy without malignancy) that was
      removed by right hemicolectomy. Extensive mesenteric infiltration and colonic
      obstruction seemed to confirm this diagnosis. Surprisingly histology revealed
      invasion by sclerosing mesenteritis. The differential diagnoses include
      inflammatory pseudotumor, tumor-like fibromatosis at traumatized sites,
      idiopathic retroperitoneal fibromatosis, sclerosing malignant lymphoma,
      liposarcoma and drug-induced sclerosing mesenteritis, as well as mesenteric
      infiltration and metastases. Though preoperative diagnosis is not possible in
      most cases, the intraoperative macroscopic appearance and the histopathologic
      picture are conclusive.

PMID- 11469100
TI  - [Peripheral arterial reconstruction].

PMID- 11469101
TI  - [Simultaneous explanation by the Professional Association of German Surgeons and
      the Professional Association of Physicians for Orthopedics. Physician elective
      treatment in the DRG system].

PMID- 11469102
TI  - [Evaluation faulty admission--an element of quality assurance in self governing].

PMID- 11469103
TI  - [Legal problems of the elderly patients. Address on 23 February 2001 on the
      occasion of the 25th Berlin Surgery Congress on the topic of "Surgery in the
      elderly"].

PMID- 11469104
TI  - [Education in intraluminal endoscopy--experiences up to now].

PMID- 11469105
TI  - [Stipends for established surgeons from the Wolfgang Muller-Osten legacy].

PMID- 11469106
TI  - Facility inspections: how often and following which guidelines?

PMID- 11469107
TI  - Do you need a cerebrum to feel pain?

PMID- 11469108
TI  - What's your diagnosis? Bilateral head swelling in a male beagle. Masticatory
      muscle myositis (acute form).

PMID- 11469109
TI  - A novel approach for addressing enrichment and exercise for dogs in a teaching
      institution.
AB  - The author describes a pilot Animal-Assisted Activities (AAA) program that
      provides additional enrichment and exercise for beagles maintained for
      educational purposes. In addition, the program educates the community on research
      involving animals, provides positive interactions between the institution and the
      community, and develops community service skills in students.

PMID- 11469110
TI  - Community outreach: a focus on bioethics.
AB  - The author suggests that the infusion of bioethics into all aspects of the animal
      research community's work provides a framework for making decisions. Such
      deliberations, grounded in ethical theories and principles, can help to reinforce
      the position that both the research process and the people involved in it are
      morally sound. Pro-biomedical research groups around the country are therefore
      investing time and effort in bioethics training.

PMID- 11469111
TI  - Community outreach begins inside.
AB  - While vocal animal rights activists are widely recognized as a potential danger
      to biomedical research, much less attention is paid to anti-research sentiments
      that may be inadvertently propagated by those working within the biomedical
      research field. The author explores a number of "internal outreach" programs to
      educate employees about the importance of the work they do, as well as the
      necessity of using animals.

PMID- 11469112
TI  - Community outreach: a call for cultural change.
AB  - The author proposes a cultural shift within biomedical research, suggesting that
      scientists should view the use of any animal as a privilege only to be used under
      careful scrutiny and after a thorough search for alternatives. He further
      suggests that the IACUC can be a vehicle for such a change.

PMID- 11469113
TI  - Review of statistical methods for QTL mapping in experimental crosses.
AB  - Identification of quantitative trait loci (QTLs) in experimental animals is
      critical for understanding the biochemical bases of complex traits, and thus for
      the identification of drug targets. The author reviews the basic statistical
      methods for mapping QTLs in experimental crosses and comments on a number of the
      statistical issues to consider in the application of these methods.

PMID- 11469114
TI  - A structural model of acculturation and mental health status among Chinese
      Americans.
AB  - This study examined the role of acculturation and its direct and indirect impact
      on depressive symptom severity through various correlates, including
      socioeconomic status (SES), stress, social support, personality negativity, and
      physical health perception. Using structural equation modeling, the proposed
      model was tested with 983 employed Chinese Americans from a representative
      community sample, the majority of whom were immigrants. The results demonstrated
      that acculturation, correlated with SES, contributed to depressive symptom
      severity only through indirect pathways. Higher acculturation was found
      associated with higher stress that in turn contributed to more elevated
      depressive symptoms. On the other hand, higher acculturation was also found
      strongly correlated with higher SES, which was associated with lower depressive
      symptoms directly or indirectly through several mediators. Better support, lower
      personality negativity, better health perception, and lower stress were found
      mediating the relationship between higher SES and lower depressive symptom
      severity. The simultaneous multigroup analysis showed that the final model was
      comparable for both men and women with very few differences.

PMID- 11469115
TI  - Determinants of social support among low-income mothers: a longitudinal analysis.
AB  - This study examined the reciprocal relationships between perceived mastery,
      stress, and three functional areas of social support: tangible support,
      informational support, and belongingness support. Data were collected during two
      face-to-face interviews with a sample of low-income, primarily African-American
      mothers, conducted approximately 1 year apart. Consistent with predictions,
      initial levels of mastery predicted higher subsequent levels of instrumental
      social supports (tangible and advice support), but were unrelated to belonging
      support. Conversely, initial levels of tangible support were predictive of later
      mastery. Perceived stress did not account for any additional variance in
      subsequent support, although initial levels of belonging support only did predict
      reduced stress at Time 2. Results suggest that successful attempts to garner
      instrumental supports is an important contributor to individuals' sense of self
      efficacy, at the same time, self-efficacy leads to more successful use of
      existing social support systems. These findings point to the importance of having
      both available tangible support networks as well as close emotional supports for
      low-income parents. The importance of using longitudinal, multidimensional
      analyses to better understand the social support process is discussed.

PMID- 11469116
TI  - Work attitudes, employment barriers, and mental health symptoms in a sample of
      rural welfare recipients.
AB  - Most of the extant research on welfare reform has neglected to consider the
      experiences of families in rural settings. Fifty women receiving welfare for
      their dependent children in a rural community were interviewed about their work
      experiences and aspirations, barriers to employment and service use, as well as
      mental health and social support. The findings indicate that the majority of
      participants were connected to the labor force and expressed positive attitudes
      about work. Barriers to employment (lack of available jobs, child care) and
      service use (transportation, inconvenient office hours) were endorsed. Perceived
      social support was negatively related to depression symptoms and positively
      related to self-efficacy and self-esteem. The importance of understanding the
      life experiences of welfare recipients in different contexts is discussed.

PMID- 11469117
TI  - Examining the effectiveness of a community-based self-help program to increase
      women's readiness for smoking cessation.
AB  - This study investigated the effectiveness of two components of a smoking
      cessation intervention: a reading manual and a series of televised programs.
      Female smokers in the Chicago metropolitan area with a high school education or
      less were interviewed at 4 different times: baseline, immediate postintervention,
      and 6 and 12 months. We examined the effects of several baseline measures (race,
      age, number of cigarettes smoked, and stage of readiness to change) and exposure
      to the intervention components on subsequent stage of change. Race, baseline
      smoking rate, baseline stage, and exposure to both intervention components had
      direct effects on stage at immediate postintervention, with both intervention
      components increasing readiness to quit. Furthermore, exposure to the manual
      interacted with baseline stage, such that the manual benefited women at earlier
      stages more than women at later stages. Effects of both components were sustained
      at 6 months, and the effects of the manual were sustained at 12 months.

PMID- 11469119
TI  - Lung transplantation in patients with CF.

PMID- 11469118
TI  - The psychological sense of economic hardship: measurement models, validity, and
      cross-ethnic equivalence for urban families.
AB  - Poverty is a community stressor that disproportionally affects ethnic minority
      families. One aspect of programmatic research on poverty focuses on the
      psychological sense of economic hardship. In a study of 319 African American,
      European American, and Mexican American urban families, parents completed
      objective measures of economic status and scales of perceived economic hardship
      that were adapted from previous research. Measurement models identified a
      coherent construct of psychological sense of economic hardship that was
      essentially equivalent for mothers and fathers, English- and Spanish-speaking
      Mexican Americans, and the 3 ethnic groups. In support of the validity of this
      construct, relations between objective indicators of economic status and
      perceived economic hardship showed equivalence across these same groups.

PMID- 11469120
TI  - PKU treatment in 1950.

PMID- 11469121
TI  - Domestic violence in the workplace.

PMID- 11469122
TI  - In defense of pediatric nurses.

PMID- 11469123
TI  - Complex regional pain syndrome.

PMID- 11469124
TI  - Poison control.

PMID- 11469125
TI  - Increased federal funding for nursing in jeopardy.

PMID- 11469126
TI  - Understanding secondary traumatic stress.

PMID- 11469127
TI  - Paradoxical reactions to benzodiazepines.

PMID- 11469128
TI  - Emergency. Palpitations.

PMID- 11469129
TI  - Myths and facts about side rails.

PMID- 11469130
TI  - Is there a nurse on board?

PMID- 11469131
TI  - Violence in the workplace. Are you prepared?

PMID- 11469132
TI  - Prospective payment comes to Medicare home health.

PMID- 11469133
TI  - Surviving the night shift.

PMID- 11469134
TI  - Assessment and treatment of patients with mental illness.

PMID- 11469135
TI  - Your role in your annual performance evaluation.

PMID- 11469136
TI  - Caring for incompetent patients and their surrogates.

PMID- 11469137
TI  - Blowing the whistle.

PMID- 11469138
TI  - Latex allergy.

PMID- 11469139
TI  - The Elder Image Scale: a method for indexing history and emotion in family
      caregiving.
AB  - Although caregiving has been studied extensively, most studies have focused on
      the activities performed by caregivers, problems encountered and caregivers'
      reactions. Less attention has been paid to measuring historical and interpersonal
      factors that may shape the situation and affect outcomes, but are not necessarily
      embedded in the role itself. The objective of this article is to report on the
      development and testing of the Elder Image Scale (EIS) which indexes the personal
      identity of the elder, the mental image the caregiver has of the elder derived
      from past associations, present observations, and the reconciliation of the past
      with present impressions. This scale was based on the Family Caregiving Dynamics
      Model and the personal image of the elder is predicted to be shaped by certain
      structural factors and to impact both the perceptions of caregivers and the
      outcomes of caregiving. This article reports on four separate investigations; six
      hundred-and-fifty-six caregivers participated. The EIS is in the semantic
      differential format. Internal consistency ranged from .92 to .98 over four
      studies. Stability after two weeks was .93 for both subscales. All correlations
      with criteria were in the direction predicted and most were significant. Known
      group comparisons showed all group differences were statistically significant as
      predicted. The EIS is internally consistent, stable and evidences construct
      validity. In addition, measuring this concept appears to have great relevance for
      explaining both perceptions of caregivers and outcomes of caregiving.

PMID- 11469140
TI  - An instrument's conceptual base: its link to theory.

PMID- 11469141
TI  - Ambulatory blood pressure monitoring: measurement implications for research.
AB  - Although blood pressure (BP) is a frequently used variable in nursing studies,
      measurements are likely to be inaccurate for a variety of reasons: incorrect
      technique, operator error, and environmental factors. Ambulatory BP monitoring
      (ABPM) reduces measurement error, is relatively easy to use, and yields many more
      BP parameters than do clinic BP measurements. The cost of equipment for ABPM
      ranges from $2,500 to $5,000 per monitor and from $2,000 to $3,000 for computer
      software. A research assistant can easily be trained to follow a standardized
      procedure. Researchers have used ABPM to study normal BP patterns, complications
      of hypertension, effects of antihypertensive drugs, and the prognosis of
      cardiovascular events. This article provides the nurse researcher with an
      introduction to this technology and an overview of information gained from
      ambulatory blood pressure monitoring.

PMID- 11469142
TI  - Item response theory in affective instrument development: an illustration.
AB  - The benefits of item response theory (IRT) analysis in obtaining empirical
      support for construct validity make it an essential step in the instrument
      development process. IRT analysis can result in finer construct interpretations
      that lead to more thorough descriptions of low- and high-scoring respondents. A
      critical function of IRT is its ability to determine the adequacy with which the
      attitude continuum underlying each dimension is assessed by the respective items
      in an instrument. Many nurse researchers, however, are not reaping the benefits
      of IRT in the development of affective instruments. The purpose of this article
      is to familiarize nurse researchers with this valuable approach through a
      description of the Facets computer program. Facets uses a one parameter (i.e.,
      item difficulty) Rasch measurement model. Data from a survey of 525 new mothers
      that assessed the psychometric properties of the Postpartum Depression Screening
      Scale are used to illustrate the Facets program. It is hoped that IRT will gain
      increased prominence in affective instrument development as more nurse
      researchers become aware of computer programs such as Facets to assist in
      analysis.

PMID- 11469143
TI  - Psychometric testing of the depressive cognition scale in women with type 2
      diabetes.
AB  - Depression is prevalent in young and middle-aged diabetic women. Although
      cognitive depressive symptoms precede the development of depression, there is no
      screening instrument to measure these symptoms in diabetic patients. This study
      tested the psychometric properties of the Depressive Cognition Scale (DCS) in a
      convenience sample of 83 women with Type 2 diabetes. Alpha coefficient for the 8
      item scale was .85, and the average inter-item correlation coefficient was .42.
      Construct validity was supported by correlations in the expected directions
      between the DCS and measures of learned resourcefulness, depressive symptoms, and
      health practices. Factor analysis presented a single dimension of 8 items. These
      findings suggest that the DSC will be useful in identifying patients with chronic
      conditions such as diabetes who are at risk for the development of clinical
      depression.

PMID- 11469144
TI  - Documenting patterns of nursing interventions using cluster analysis.
AB  - Use of inferential statistics in research applications of the Nursing
      Intervention Classification has been rare, yet use of these statistical
      techniques is needed to answer questions related to intervention patterns. Using
      data from a descriptive study of 3,733 visits documented by 19 adult nurse
      practitioner students, hierarchical agglomerative cluster analysis was used to
      determine whether meaningful nursing intervention patterns could be depicted.
      Eight intervention clusters were derived, replicated, and validated. Clusters of
      intervention classes differed in the type of nursing and medical diagnosis,
      amount of time the nurse spent during the visit, cost of visit, and the age of
      the patient. Clustering supported the utility of standardized nursing diagnosis
      and intervention typologies to identify actual practice patterns of adult nurse
      practitioner students. Cluster analysis is a valuable data analysis strategy when
      analyzing multiple related variables.

PMID- 11469145
TI  - Development of the Misener Nurse Practitioner Job Satisfaction Scale.
AB  - The purpose of this study was to construct a reliable and valid instrument to
      measure job satisfaction among nurse practitioners (NP). The methodological
      approach consisted of a literature review and modification of an extant
      instrument (Mueller/McCloskey, 1990) to reflect primary care, followed by
      augmentation and validation of the items suggested by nurse practitioner faculty
      members and Master's prepared nurse practitioners. A 77-item scale was developed
      and mailed to 413 NPs recognized by the state boards of nursing in two states.
      Usable returns were received from 342 (83%) NPs. Items were reviewed for validity
      prior to field-testing the instrument. The 77 items were subjected to exploratory
      factor analysis to support construct explication using the maximum likelihood
      method of extraction and a promax rotation. An eigenvalue cutoff of 1.0 and item
      to-factor loadings of at least .35 were criteria that guided item retention.
      Thirty-three items were deleted. The resultant six factors were named: (a) intra
      practice partnership/collegiality; (b) challenge/autonomy; (c) professional,
      social, and community interaction; (d) professional growth; (e) time; and (f)
      benefits. The six factors (subscales) produced internal consistency reliability
      estimates of .94, .89, .84, .86, .83, and .79, respectively. The 44 retained
      items were used to create the final version of the Misener Nurse Practitioner Job
      Satisfaction Scale (MNPJSS), with a possible maximum score of 264 using a 6-point
      Likert-type scale.

PMID- 11469146
TI  - Shrinking civil rights of alleged sexually violent predators.

PMID- 11469147
TI  - The erosion of medical leadership in public health.

PMID- 11469148
TI  - The people's campaign against health care counter-reforms in Spain.
AB  - Since 1996, when the conservative Partido Popular was elected in Spain, it has
      attempted to weaken and dismantle the national health service. It has focused on
      three areas: privatization of health facilities and services, increasing patient
      copayments and decreasing publicly financed benefits, and increasing the role of
      private insurance in health coverage and care. A major role in this neoliberal
      strategy has been the creation in one of the regions of "Fundaciones,"
      independent substitutes for NHS facilities and services, which are essentially
      copies of the "Trusts" developed by the Conservative government in the U.K. The
      paper describes the development of a broad people's movement which campaigned
      successfully to combat the "Fundaciones"; these were returned to the regional
      public sector, and the conservative government in Madrid announced they would
      abandon their previous principal policy of transforming public hospitals into
      "Fundaciones."

PMID- 11469149
TI  - The epidemiologic tradition: the Wade Hampton Frost Lecture.

PMID- 11469150
TI  - Population and gender equity.

PMID- 11469151
TI  - Egalitarian aspects of medical and social services.
AB  - Unmet needs for medical and social services are present in all socioeconomic
      strata, but workers and poor people suffer most. Satisfaction of the needs of
      these groups could help to narrow the differences in health and survival between
      social classes. As needs for services change with the historical period, age, and
      changing attitudes to help-seeking in younger generations, we require cohort
      studies of needs measured directly in random samples of the population. Cohort
      analyses could form the basis for future plans to provide services equitably.

PMID- 11469152
TI  - Handgun sales, beer sales, and youth homicide, California, 1972-1993.
AB  - Whether regulating access to firearms and alcohol will reduce violent injuries is
      an important policy question. Empirical answers are difficult to obtain because
      only observational data are available. The present study estimated the
      association of firearm sales and alcohol sales with subsequent homicides, after
      adjusting statistically for potential confounders (e.g., unemployment rates)
      using California data from 1972 through 1993. Handgun sales and beer sales were
      lagged one year and used to explain variation in the homicides of Californians
      (e.g., 1990 sales were used to explain 1991 homicides). Differences across
      population groups were investigated, with a focus on 15- to 34-year-olds, the
      highest risk age group. Even when taking potential confounders in the base
      population into account, beer sales and handgun sales generally are associated
      positively one year later with homicide, particularly among young men. Reducing
      beer sales may reduce homicides. And, although they represent a small fraction of
      existing firearms, regulating the number of handguns sold may reduce the number
      of homicides.

PMID- 11469153
TI  - Reprivatizing pharmaceutical supplies in Africa.
AB  - Perhaps no part of the health system is as imperiled by neoliberal economic
      reforms as the public drug sector. The national bill for pharmaceuticals can
      claim one-third of a developing country's annual health budget. This article
      describes the essential drugs program created by WHO in the 1980s to protect
      financially reduced ministries of health from the high prices charged by
      multinational pharmaceutical companies. It describes the backlash from the World
      Bank and UNICEF, which launched the Bamako Initiative and other community
      financing schemes and revolving drug plans in which individuals, families or
      community groups buy drugs above the wholesale purchase price; clinics use the
      proceeds to maintain drug supplies and subsidize other health services. When this
      plan failed, the Bank proposed outright privatization of drug purchase and
      supply, returning power to the multinational suppliers. The article ends with a
      consideration of patents and the new intellectual property rights as they pertain
      to pharmaceutical production in Africa.

PMID- 11469154
TI  - The fight for water and democracy: an interview with Oscar Olivera.

PMID- 11469155
TI  - Genetic and environmental influences on the relationship among combat exposure,
      posttraumatic stress disorder symptoms, and alcohol use.
AB  - The role of genetic and environmental influences on the relationship between
      combat exposure, posttraumatic stress disorder (PTSD) symptoms, and alcohol use
      were examined in 4072 male-male twin pairs who served in the United States
      military during the Vietnam era (1965-1975). Results indicate that the
      relationship between combat and alcohol use and between PTSD symptom factors and
      alcohol use were both substantially influenced by genetic factors. Findings are
      most consistent with a shared vulnerability model for the etiology of the
      association between PTSD symptoms and alcohol use. Specific unique environmental
      factors were more important than genetic factors for PTSD symptoms, and both
      factors were equally important for alcohol use. Further support is also found for
      the role of the unique environment in PTSD symptoms.

PMID- 11469156
TI  - Reconstructing trauma memories: a prospective study of "amnesic" trauma
      survivors.
AB  - The purpose of this study was to investigate memory for trauma in patients who
      were initially amnesic of the trauma as a result of mild traumatic brain injury
      (MTBI). Motor vehicle accident survivors who sustained a MTBI were assessed for
      their memory within 1-month posttrauma (n = 79) and again at 2-years posttrauma
      (n = 50). Consistent with their brain injury, all patients reported significant
      amnesia of their accident at initial assessment. At 2-year posttrauma, 40% were
      able to remember their accident. Reporting memory for the trauma was associated
      with shorter duration of posttraumatic amnesia. These findings suggest that
      people reconstruct memories of trauma in the absence of complete encoding of the
      experience. Possible mechanisms for memory reconstruction are considered.

PMID- 11469157
TI  - Posttraumatic stress disorder in rape victims: autonomic habituation to auditory
      stimuli.
AB  - Impaired capacity for physiological habituation may contribute to the persistence
      of PTSD. Habituation of autonomic responses to auditory tones was examined in 43
      women in three groups: 14 adult female rape survivors with chronic PTSD, 11
      without PTSD, and a comparison group of 18 who had not been raped. There were no
      significant differences among the groups in baseline cardiac or electrodermal
      activity. The PTSD group showed significantly slower electrodermal habituation,
      as measured by trials to extinction and percentage of nonhabituators, than did
      the comparison groups. The present study found slower habituation of
      electrodermal responses for PTSD rape victims to neutral stimuli than for non
      PTSD victims and nonvictims.

PMID- 11469158
TI  - Working memory in posttraumatic stress disorder--an event-related potential
      study.
AB  - This study examined ERP topography during the updating and the utilization of
      working memory in subjects with PTSD. Event-related potentials of 18 participants
      with PTSD and 18 controls were recorded from 32 scalp electrodes during an
      auditory target detection task requiring the constant updating of target
      identity. Midline N2 and P3 abnormalities previously noted in PTSD during target
      detection were replicated. Scalp topographic data revealed sustained reduction in
      activity over the right hemisphere during working memory updating. Executive
      processes were associated with brief but widespread right hemisphere reductions
      during the P3, followed by sustained, bilateral reduction frontally. This study
      identifies an abnormal pattern of cortical network function during both the
      updating and use of working memory in PTSD.

PMID- 11469159
TI  - Assessment of exposure to political violence and other potentially traumatizing
      events. A critical review.
AB  - This paper focuses on the common use of internal-consistency reliability, test
      retest, and interrater correlations based on counts of events, events sampling,
      and factor-analytic techniques in assessment of exposure to political violence
      and other potentially traumatizing events. The author attributes the continued
      use of these strategies to a tendency among researchers to identify items from
      conventional events lists as effect indicators. Through a discussion of four
      alternative measurement models, the rationale is provided for the proposition
      that exposure to political violence and similar constructs should be treated as
      composite variables with causal indicators, rather than as latent variables with
      effect indicators.

PMID- 11469160
TI  - Effect of timing of critical incident stress debriefing (CISD) on posttraumatic
      symptoms.
AB  - Seventy-seven civilian employees who were victims of robbery were randomly
      assigned to either an immediate (< 10 hr) or delayed (> 48 hr) debriefing group,
      using the J. Mitchell (1983) CISD protocol. Scores on the Posttraumatic Stress
      Diagnostic Scale were obtained at 4 time intervals: debrief, 2 and 4 days post
      debrief, and 2 weeks postrobbery. The number and severity of symptoms did not
      differ at debrief, but were lower for the immediate than for the delayed group at
      each subsequent time interval. The number and severity of symptoms declined
      across time intervals; however, although this reduction was pronounced for the
      immediate group it was minimal for the delayed group. The results supported use
      of immediate debriefing with this type of incident and victim.

PMID- 11469161
TI  - Development of a depersonalization severity scale.
AB  - Our aim was to develop a clinician-rated scale assessing depersonalization
      severity for use in clinical trials of Depersonalization Disorder and trauma
      related disorders in general. The 6-item Depersonalization Severity Scale (DSS)
      was administered to 63 participants with DSM-IV Depersonalization Disorder as
      diagnosed by the SCID-D, and its psychometric properties were examined. The
      sensitivity of the DSS and of the Dissociative Experiences Scale (DES) to
      treatment change was assessed in blinded, controlled settings. Individual items
      were widely distributed across the severity range. Interrater reliability was
      excellent and internal consistency was moderate. The DSS had high convergent and
      discriminant validity and was sensitive to treatment change. The DES was also
      sensitive to treatment change. We recommend piloting the DSS in future treatment
      trials of trauma-spectrum disorders.

PMID- 11469162
TI  - Child sexual abuse, peer sexual abuse, and sexual assault in adulthood: a multi
      risk model of revictimization.
AB  - This study explored the predictors and consequences of sexual assault occurring
      after the age of 16 years in a nonclinical sample of women. Child sexual abuse
      occurring before the age of 16 years was the only predictor of later sexual
      assault among comorbid risk factors. Peer sexual abuse, number of perpetrators,
      age at time of sexual abuse, and severity of sexual abuse did not increase the
      risk for later sexual assault. Adult sexual assault victims showed lower levels
      of mental health functioning than did survivors of child or peer sexual abuse. We
      discuss a specificity model of revictimization and the differential effects of
      child, peer, and adult sexual trauma on the developmental trajectory of sexual
      violence and psychosocial functioning.

PMID- 11469163
TI  - Predictors of PTSD symptom severity and social reactions in sexual assault
      victims.
AB  - Demographics, assault variables, and postassault responses were analyzed as
      correlates of PTSD symptom severity in a sample of 323 sexual assault victims.
      Regression analyses indicated that less education, greater perceived life threat,
      and receipt of more negative social reactions upon disclosing assault were each
      related to greater PTSD symptom severity. Ethnic minority victims reported more
      negative social reactions from others. Victims of more severe sexual
      victimization reported fewer positive, but more negative reactions from others.
      Greater extent of disclosure of the assault was related to more positive and
      fewer negative social reactions. Telling more persons about the assault was
      related to more negative and positive reactions. Implications of these results
      for developing contextual theoretical models of rape-related PTSD are discussed.

PMID- 11469164
TI  - Western conceptualizations and Eastern experience: a cross-cultural study of
      traumatic stress reactions among Tibetan refugees in India.
AB  - This study investigated the nature and impact of traumatic experiences among
      Tibetan refugees in India. It explored the applicability of western
      conceptualizations of reactions to traumatic events among this cultural group. A
      randomly selected sample of refugee camp students was assessed on measures of
      psychological and physical complaints, and on impact as well as severity of
      traumatic experiences. Respondents had experienced multiple traumatic events. The
      majority reported ongoing health problems. More than half demonstrated symptoms
      of intrusion-avoidance. Those with more traumatic experiences reported more
      symptoms of anxiety and depression (psychologically and, particularly,
      somatically manifested). Cultural differences in types of experienced traumatic
      events and manifestations of distress are discussed, as are implications for
      cross-cultural trauma research using western conceptualizations and instruments.

PMID- 11469165
TI  - Role of major lifetime stressors in patients' and spouses' reactions to cancer.
AB  - This study examined the role of number of major lifetime stressors (e.g., rape,
      abuse), and the perceived resolution of those stressors, in cancer patients' (n =
      54) and spouses' (n = 30) appraisals and current mood. We hypothesized that a
      high number of lifetime stressors, and low resolution ratings, would be
      associated with more distress and more negative appraisals of the cancer.
      Hierarchical regression analyses showed that number of lifetime stressors was a
      positive predictor of patients' ratings of the cancer's threat, and a positive
      predictor of their spouses' anger. Mean resolution ratings were a significant
      positive predictor of spouses' positive affect. The findings suggest that
      experience with previous stressors affects an individual's reactions to cancer.

PMID- 11469166
TI  - Multivariate assessment of explicit memory function in combat veterans with
      posttraumatic stress disorder.
AB  - Declarative memory impairment is a frequent complaint of patients suffering from
      posttraumatic stress disorder (PTSD). We assessed memory, attention, visual
      spatial skills, and executive function in Vietnam combat veterans with (n = 19)
      and without (n = 13) PTSD. Although PTSD subjects demonstrated a "generalized
      impairment" relative to non-PTSD subjects on a majority of tasks, only attention
      and memory provided unique and independent prediction of PTSD versus non-PTSD
      status. Our findings suggest that memory functioning represents a neurocognitive
      domain of specific relevance to the development of PTSD in trauma-exposed
      individuals, which can be distinguished from generalized attentional impairment
      as well as the effects of trauma exposure severity, IQ, comorbid depression,
      history of alcohol use, and history of developmental learning problems.

PMID- 11469167
TI  - Treatment of combat-related nightmares using imagery rehearsal: a pilot study.
AB  - Posttraumatic nightmares are a hallmark of PTSD and distinct from general
      nightmares as they are often repetitive and faithful representations of the
      traumatic event. This paper presents data from a pilot study that examined the
      use of Imagery Rehearsal in treating combat-related nightmares of 12 Vietnam
      veterans with PTSD. Three treatment groups, comprising 4 veterans in each,
      completed standardised treatment across 6 sessions. Treatment effects were
      investigated using nightmare diaries and established instruments, including the
      IES-R, BDI, BAI, and SCL-90-R. The data demonstrate significant reductions in
      nightmares targeted, and improvements in PTSD and comorbid symptomatology. The
      paper recommends that, on the basis of the promising preliminary data, a
      randomised control trial be established to assess imagery ability and attitude
      toward nightmares.

PMID- 11469168
TI  - Vaccines under fire: the importance of perspective.

PMID- 11469169
TI  - The stubborn facts of vaccine safety.

PMID- 11469170
TI  - How vaccine safety is monitored before and after licensure.

PMID- 11469171
TI  - Explaining the risks and benefits of vaccines to parents.

PMID- 11469172
TI  - Measles-mumps-rubella vaccine and autism: the rise (and fall?) of a hypothesis.

PMID- 11469173
TI  - Vaccine information statements in the pediatric office.

PMID- 11469174
TI  - A screening questionnaire for contraindications to vaccination.

PMID- 11469175
TI  - Resident's column: a resident's view of the ethics and morality of immunization
      consent.

PMID- 11469176
TI  - A mother's view: my daughter's vaccine story.

PMID- 11469177
TI  - Partners: serendipity in arbovirus research.
AB  - A review of 60 years of research on mosquito-borne arboviruses in the Western
      U.S.A. revealed a number of instances when serendipity influenced the development
      of new concepts or novel approaches to solve ecological or epidemiological
      problems. Eight such events were selected as examples. The need for effective
      mosquito traps to collect live mosquitoes to be tested for virus infection posed
      design problems and also led to the use of CO2 (dry ice) as a mosquito
      attractant. This research also led to identification of Culex tarsalis as a
      primary target for vector control programs in the western U.S.A. Attendance at a
      movie led to development of fluorescent dusts to mark mosquitoes for studies of
      their numbers, life tables and movements. Knowledge of vector-virus associations
      was used to influence state legislative action to provide funding for vector
      control and further discovery of vector-virus associations. Derivation of the
      term "Arbovirus" started as laboratory jargon and evolved into being the
      classification for over 500 vector-borne viruses. Sociobiological changes
      resulting from the use of television and air conditioning fortuitously decreased
      exposure of California residents to vector attack. These two changes were
      introduced into households in California in the early 1950s. The prime time when
      C. tarsalis, the primary vector of encephalitis, bites people is around sundown
      which also is primetime for television watching. These sociological changes are a
      valuable adjunct to vector control programs.

PMID- 11469178
TI  - Habitat preference of host-seeking Coquillettidia perturbans (Walker) in relation
      to birds and eastern equine encephalomyelitis virus in New Jersey.
AB  - Coquillettidia perturbans (Walker) has been implicated as a bridge vector of
      eastern equine encephalomyelitis virus in North America. Eastern equine
      encephalomyelitis virus epizootics occur regularly in wild birds in New Jersey
      with little or no involvement of susceptible dead end hosts even though high
      populations of Cq. perturbans are present. Several factors may limit eastern
      equine encephalomyelitis (EEE) virus transfer from birds to mosquito bridge
      vectors like Cq. perturbans (Walker), including bird/mosquito density,
      differences in bird/mosquito habitat preference, mosquito host preference,
      mosquito host-seeking behavior and mosquito avoidance behavior by birds. Our
      investigations focused on the host-seeking activities of Cq. perturbans at
      Colliers Mills Wildlife Management Area in Ocean County, New Jersey. We first
      examined the abundance of host-seeking Cq. perturbans at a height of 1.0 m in
      each of three habitats: forest, open field and marsh. We collected significantly
      more mosquitoes in the forest as compared to the marsh. Forest and field
      collections did not differ significantly from one another nor did field and
      marsh. Second, we examined the temporal and vertical distribution of host-seeking
      Cq. perturbans in a sylvan habitat at three heights (1.0, 2.5, and 6.0 m) from
      dusk to dawn. We found that Cq. perturbans did significantly more host-seeking
      during the night period than either the evening or morning. Host-seeking
      mosquitoes also tended to stay near the ground and at no time did they ascend
      into the forest canopy. Host-seeking Cq. perturbans and their apparent spatial
      disparity to roosting/nesting birds are discussed as a possible barrier to the
      transmission of EEE virus in New Jersey.

PMID- 11469179
TI  - Thermal application of Bacillus thuringiensis serovar israelensis for dengue
      vector control.

PMID- 11469180
TI  - Entomopathogenic activities of environmental isolates of Bacillus thuringiensis
      against dipteran larvae.
AB  - Twenty-five field isolates of Bacillus thuringiensis from the Lower Silesia
      region of Poland, the Osola plain, and phylloplane niches and soil samples from
      the Karkonosze National Park were tested for insecticidal activity against larvae
      of the dipterans Aedes aegypti, Drosophila melanogaster and Musca domestica. The
      spore-crystal mixture of B. thuringiensis finitimus (soil isolate) killed nearly
      half of the fourth instar larvae of Ae. aegypti. Similar mortality of between 39
      61% was recorded after treatment with two phylloplane isolates belonging to
      biochemical type I of B. thuringiensis (subsp. japonensis, yoso and
      jinghongiensis) and type IV (subsp. tochigiensis,). The effect of B.
      thuringiensis wratislaviensis H-47 was lowest, with larval mortality ranging from
      7-28%. The susceptibility of D. melanogaster, evaluated as percentage of larvae
      that did not survive to adulthood, varied between 0-38% and 0-45% at dosages of
      0.5 and 1 ml, respectively. The LC50s ranged from 5.07 x 10(9) to 1.04 x 10(11)
      spore-crystal mixture. The LC50s for M. domestica larvae were 4.1-4.8 x 10(8)
      spores/ml of B. thuringiensis finitimus and the phylloplane strain KpC1 (I type)
      and 2.9 x 10(9) for the phyloplane representative of group I. Generally, all
      tested isolates showed the most activity against common fly larvae. The highest
      (64-81% mortality) was observed after treatment with both phylloplane (OpPs1,
      KpF3, KpC1) and soil isolates (KsAc1) of biochemical type I as well as B.
      thuringiensis finitimus (type III).

PMID- 11469181
TI  - Aedes aegypti: size, reserves, survival, and flight potential.
AB  - Female Aedes aegypti of small and large body sizes were fed ad libitum from
      eclosion with eight different concentrations of sucrose from 0.1% to 50%; females
      were also starved with access to water. For each experiment we determined the
      survivorship of such populations. The 90%, 50%, 10%, and maximal survivorships
      followed linear regressions with the logarithm of the sucrose concentration. For
      each condition we measured the extent of synthesis of glycogen and lipid
      reserves. There was a critical sucrose concentration of 0.5% for both size
      classes: lower concentrations were of no nutritive effect, and all higher
      concentrations extended survivorship and allowed reserve synthesis. With respect
      to the teneral value, and normalized for body size, the maximal amounts of
      glycogen increased 2-3-fold within one week, whereas lipogenesis increased 3-5
      fold requiring two weeks. Solid sugar cubes could also be utilized as long as
      drinking water was available, but synthesis of additional reserves failed. Flight
      mill experiments revealed the temporal flight pattern, its maturation after
      eclosion, and the maximal flight performances. Flights shorter than 1000 m per
      female per night were considered as low activities, whereas flights lower than
      1000 m represented strong vigorous flights. Maximal distances were from 11-18
      km/female/night. Periods of continuous flights lasted between 2-9 hr per female
      (mean 2.2 hr). Maximal flight performances were gradually reached within the
      first and third day of eclosion. Mean caloric energy consumption during flight
      was 33% to 44% of the pre-flight glycogen, accompanied by lipid reductions of 9%.
      Evidently, feeding on carbohydrates allows extended flight activities of this
      species and is essential for survival in the absence of blood meals.

PMID- 11469182
TI  - Integrated pest management and allocation of control efforts for vector-borne
      diseases.
AB  - Applications of various control methods were evaluated to determine how to
      integrate methods so as to minimize the number of human cases of vector-borne
      diseases. These diseases can be controlled by lowering the number of vector-human
      contacts (e.g., by pesticide applications or use of repellents), or by lowering
      the proportion of vectors infected with pathogens (e.g., by lowering or
      vaccinating reservoir host populations). Control methods should be combined in
      such a way as to most efficiently lower the probability of human encounter with
      an infected vector. Simulations using a simple probabilistic model of pathogen
      transmission suggest that the most efficient way to integrate different control
      methods is to combine methods that have the same effect (e.g., combine treatments
      that lower the vector population; or combine treatments that lower pathogen
      prevalence in vectors). Combining techniques that have different effects (e.g., a
      technique that lowers vector populations with a technique that lowers pathogen
      prevalence in vectors) will be less efficient than combining two techniques that
      both lower vector populations or combining two techniques that both lower
      pathogen prevalence, costs being the same. Costs of alternative control methods
      generally differ, so the efficiency of various combinations at lowering human
      contact with infected vectors should be estimated at available funding levels.
      Data should be collected from initial trials to improve the effects of subsequent
      interventions on the number of human cases.

PMID- 11469183
TI  - Field evaluation of an insect growth regulator, pyriproxyfen, against Aedes togoi
      larvae in brackish water in South Korea.
AB  - The granular formulation of 0.5% pyriproxyfen was evaluated for inhibition of
      emergence of Aedes togoi in brackish water of rock pools near a coastal area in
      Pusan, South Korea. Complete adult emergence inhibition in 4th-stage larval and
      pupal isolations was affected from 5-40 days at 0.05 mg/l after treatment. Most
      inhibition rates were over 80% throughout the test period at all test
      concentrations of pyriproxyfen except 61.0% and 67.5% of inhibition rates at 0.01
      mg/l at 52 days and 62 days after treatment, respectively. It is suggested that
      the dose for successive control of Ae. togoi for long-term might be 0.05-0.1 mg/l
      of 0.5% pyriproxyfen granules.

PMID- 11469184
TI  - Effects of nutritional factors and soil addition on growth, longevity and
      fecundity of the tadpole shrimp Triops newberryi (Notostraca: Triopsidae), a
      potential biological control agent of immature mosquitoes.
AB  - The notostracan tadpole shrimp (TPS) Triops newberryi Packard has potential to be
      used as a biocontrol agent of immature mosquitoes. Eggs, nymphal or adult shrimps
      are considered to be the stages for field introduction. To yield good growth of
      the shrimp and high production of shrimp eggs under artificial conditions,
      nutritional requirements of TPS for growth, survival and fecundity need to be
      elucidated. In the laboratory, we evaluated various nutritional and edaphic
      regimens, such as soil alone, mosquito larvae or rabbit pellets alone and various
      combinations of these three components for culturing. These factors influenced
      the growth, longevity and egg production profoundly. It was shown that the
      simulated natural conditions, i.e. full combination of all three factors, yielded
      the largest TPS with longest survival and highest egg production, followed by the
      combinations of any two components. Any single component, soil, mosquito larvae,
      or rabbit pellets, did not result in good growth, survival and egg production. By
      formulating optimal rearing substrates, this species of TPS will yield large
      numbers of all stages for experimentation and field introductions. Under optimal
      conditions, they mature in 7-8 days and survive for about one month. Each TPS is
      capable of producing up to 1,000 eggs during its lifetime. These studies
      developed nutritional regimens for TPS mass culturing procedures, where the eggs,
      nymphal and adult TPS can be mass cultured for field introduction and stocking in
      mosquito developmental sites.

PMID- 11469185
TI  - A review of the North American Catallagia Rothschild, 1915, with the description
      of a new species (Siphonaptera: Ctenophthalmidae: Neopsyllinae:
      Phalacropsyllini).
AB  - Catallagia duffneri Lewis and Haas is described from the Pinaleno Mountains of
      southeastern Arizona. The 15 known North American members of the genus are
      illustrated, a key to them is included and the individual species are discussed
      with respect to their taxonomic characters, host preferences and geographic
      distribution.

PMID- 11469186
TI  - Geographical distribution of rodent-associated hantaviruses in Texas.
AB  - The purpose of this study was to increase our knowledge of the geographic
      distribution and natural host range of hantaviruses in Texas, southeastern New
      Mexico, and Mexico. Blood samples from 3,225 wild rodents, representing 34
      species, were tested for hantavirus antibody (IgG), using an enzyme-linked
      immunosorbent assay. Hantavirus antibody was found in one or more rodents from
      each of 13 counties in Texas, Otero County in southeastern New Mexico, and Mexico
      State (central Mexico). The 133 antibody-positive rodents included seven
      Peromyscus species (P. attwateri, P. boylii, P. hylocetes, P. leucopus, P.
      maniculatis, P. melanotis, and P. pectoralis), Sigmodon hispidus, Oryzomys
      palustris, two Reithrodontomys species (R. fulvescens and R. megalotis), Neotoma
      albigula, and Perognathus merriami. This study provides further evidence that
      rodent-associated hantaviruses are geographically widely distributed in Texas.
      The discovery of antibody in P. hylocetes and P. melanotis is evidence that
      peromyscine rodents in Mexico are naturally associated with viruses belonging to
      the genus Hantavirus.

PMID- 11469187
TI  - Composition and biting activity of Anopheles (Diptera: Culicidae) attracted to
      human bait in a malaria endemic village in peninsular Malaysia near the Thailand
      border.
AB  - Nine species of Anopheles mosquitoes were collected biting humans indoors and
      outdoors in a malaria endemic village in northern Peninsular Malaysia. Outdoor
      biting was higher than that observed indoors. Biting of An. maculatus was
      observed throughout the night. Peak indoor biting occurred at 2130 h while
      outdoor biting was higher after midnight. Outdoor biting of Anopheles
      barbirostris and An. sinensis was observed throughout the night with several
      peaks after the second half of the night. Outdoor biting activities of An. kochi
      and An. philippinensis were primarily active after dusk and steadily declined
      after 2130 h.

PMID- 11469188
TI  - Repellency of volatile oils from plants against three mosquito vectors.
AB  - Volatile oils extracted by steam distillation from four plant species (turmeric
      (Curcuma longa), kaffir lime (Citrus hystrix), citronella grass (Cymbopogon
      winterianus) and hairy basil (Ocimum americanum)), were evaluated in mosquito
      cages and in a large room for their repellency effects against three mosquito
      vectors, Aedes aegypti, Anopheles dirus and Culex quinquefasciatus. The oils from
      turmeric, citronella grass and hairy basil, especially with the addition of 5%
      vanillin, repelled the three species under cage conditions for up to eight hours.
      The oil from kaffir lime alone, as well as with 5% vanillin added, was effective
      for up to three hours. With regard to the standard repellent, deet alone provided
      protection for at least eight hours against Ae. aegypti and Cx. quinquefasciatus,
      but for six hours against An. dirus. However, deet with the addition of 5%
      vanillin gave protection against the three mosquito species for at least eight
      hours. The results of large room evaluations confirmed the responses for each
      repellent treatment obtained under cage conditions. This study demonstrates the
      potential of volatile oils extracted from turmeric, citronella grass and hairy
      basil as topical repellents against both day- and night-biting mosquitoes. The
      three volatile oils can be formulated with vanillin as mosquito repellents in
      various forms to replace deet (N,N-diethyl-3-methylbenzamide), the most common
      chemical repellent currently available.

PMID- 11469189
TI  - Effects of temperature on development, mortality, mating and blood feeding
      behavior of Culiseta incidens (Diptera: Culicidae).
AB  - Culiseta incidens Thomson is distributed over most of the western USA and Canada
      northward to Alaska. Because this mosquito is difficult to colonize, its biology
      has not been well investigated. We colonized this species in 1998 and studied the
      effects of temperature on various aspects of its life cycle. The time required
      for egg melanization and the duration of the egg stage were negatively correlated
      with temperature. The proportion of fertile egg rafts was temperature
      independent. An inverse relationship existed between temperature and egg hatch.
      Molting and stadium duration after hatching were temperature-dependent, with
      higher temperature accelerating development and molting. Larvae and pupae
      experienced lower mortality and higher molting success at lower temperatures.
      Survivorship of adult mosquitoes fed on sugar solution was inversely proportional
      to temperature, lethal times for 50% mortality (LT50) were greater at the lower
      temperature than at the higher temperature. Females survived longer than did
      males at all test temperatures. Because this species is eurygamous, mating only
      occurred in large cages. Mating success was also affected by temperature. At the
      test temperatures, 20 degrees C, 25 degrees C and 30 degrees C, mating started
      from 3-5 days after emergence and reached a peak on days 13-15 after emergence.
      Maximum mating rates at 20 degrees C and 25 degrees C were higher than at 30
      degrees C. Blood feeding, as indicated by cumulative feeding rates, was affected
      by cage size, mosquito age and temperature. Mosquitoes in large cages exhibited a
      much higher feeding rate than in small cages. With age, the cumulative blood
      feeding rate increased, with the highest rate at 25 degrees C, followed by 20
      degrees C and 30 degrees C. At all temperatures tested, most of the blood fed
      females were mated.

PMID- 11469191
TI  - Abstracts from the International Federation of Clinical Neurophysiology and
      affiliated societies meetings of 1999 and 2000.

PMID- 11469190
TI  - Ixodid ticks on white-tailed deer and feral swine in Florida.
AB  - A state-wide survey was conducted in Florida during the 1997-99 hunting seasons
      to examine white-tailed deer (Odocoileus virginianus) and feral swine (Sus
      scrofa) for potential indigenous vectors of the rickettsial agent of heartwater,
      Cowdria ruminantium. A total of 504 white-tailed deer and 166 feral swine was
      examined from 30 wildlife management areas across the state. Amblyomma maculatum,
      an experimental vector of C. ruminantium, was common on both deer and feral swine
      throughout the state. Of the collection of 3,169 ticks, 34.5% were Ixodes
      scapularis Say, 34.0% Amblyomma americanum (L.), 25.5% Amblyomma maculatum Koch,
      5.8% Dermacentor variabilis (Say), 0.4% Ixodes affinis Neumann, 0.03%
      Rhipicephalus sanguineus (Latreille) and 0.01% Amblyomma auricularium (Conil).
      The only exotic tick collected was A. auricularium, which is found on armadillos
      in Central and South America and is not known to be associated with any disease.
      Overall, the most prevalent species on deer were I. scapularis (51.1%) and A.
      maculatum (35.8%), with A. americanum less prevalent (16.0%) and D. variabilis
      (3.0%) and I. affinis (1.9%) rare. On feral swine, the most prevalent species
      were I. scapularis (69.7%) and D. variabilis (56.9%), with A. maculatum (16.2%)
      and A. americanum (4.6%) less common. The geographic distribution of ticks
      differed significantly throughout the state. Both A. maculatum and Dermacentor
      variabilis were more prevalent on deer from southern Florida compared to northern
      and central Florida. In contrast, A. americanum were more prevalent in northern
      and central Florida but rare in southern Florida, and I. scapularis were more
      common in southern compared to northern Florida. These geographic differences may
      reflect differences in the risk of tick-borne diseases to domestic animals,
      wildlife and humans within Florida.

PMID- 11469192
TI  - German Environment Award 2000 presented to Franz Daschner.

PMID- 11469193
TI  - Scandinavian Society for Head and Neck Oncology annual meeting. Aarhus, Denmark,
      28-30 April 2000. Abstracts.

PMID- 11469194
TI  - Hormones and Endocrine Disrupters in Food and Water: Possible Impact on Human
      Health. Proceedings from an international workshop. May 27-30, 2000, Copenhagen,
      Denmark.

PMID- 11469195
TI  - Proceedings of the 2nd International Expert Meeting on Vascular Calcifications.
      May 25-26, 2000.

PMID- 11469196
TI  - Meeting review: Pain in Europe: Third Congress of the European Federation of IASP
      Chapters. Nice, September 26-29, 2000.

PMID- 11469197
TI  - Papers presented at the ERA2000, Electrochemistry for Environmental Restoration.
      Saline Joniche, Italy, June 18-20, 2000.

PMID- 11469198
TI  - Term or whole life? The battle continues to rage.

PMID- 11469199
TI  - Continuing competency assessment & general supervision.

PMID- 11469200
TI  - Dr. David M. Carlton, Jr.: LDA President-Elect. Interview by Leigh Berry.

PMID- 11469201
TI  - Integrating the basic sciences with clinical instruction.

PMID- 11469202
TI  - Dental Medicaid program. Facts on providers, participants, reimbursements and
      cuts.

PMID- 11469203
TI  - David Hood, Secretary, Department of Health & Hospitals. Interview by Leigh
      Barry.

PMID- 11469204
TI  - The Louisiana Medicaid challenge.

PMID- 11469205
TI  - Focus on service: caring for Louisiana citizens.

PMID- 11469206
TI  - Outcome-based dentistry: it's the future.

PMID- 11469207
TI  - The Surgeon General's report on oral health.

PMID- 11469208
TI  - General supervision. Professionalism or compromise?

PMID- 11469209
TI  - Why dentists should support general supervision.

PMID- 11469210
TI  - Proceedings of the 1st European Stanley Foundation Symposium on Bipolar Disorder.
      London, United Kingdom, 24-25 September 1998.

PMID- 11469211
TI  - Forty years of the Academy of Medical Sciences of Croatia.

PMID- 11469213
TI  - [Exfoliative glaucoma].

PMID- 11469212
TI  - Why pathology?

PMID- 11469214
TI  - Does the electrocardiographic presence of Q waves influence the survival of
      patients with acute myocardial infarction?
AB  - AIMS: To compare the outcome of short- and long-term survival of patients with Q
      wave vs non-Q wave myocardial infarction. METHODS: A total of 6676 patients with
      acute myocardial infarction were enrolled on the TRAndolapril Cardiac Evaluation
      (TRACE) register between 1990 and 1992. Medical history, electrocardiographic
      diagnosis of Q wave and non-Q wave myocardial infarction, echocardiographic
      estimation of left ventricular systolic function determined as wall motion index,
      infarct complications, and survival were documented. The factors influencing the
      postmyocardial infarction outcome of these patients were studied after 30 days
      and after 8 years of follow-up, respectively. RESULTS: Cox proportional-hazard
      models demonstrated that the electrocardiographic Q waves had significant
      influence on survival during the first 30 days [risk ratio 1.4 (95% confidence
      limits 1.2-1.7)] but no influence thereafter [1.0 (0.9-1.1)]. The result was the
      same in univariate and multivariate analyses. Subgroup analysis defined by age,
      sex, wall motion index, presence of congestive heart failure, diabetes mellitus,
      arterial hypertension, subsequent myocardial infarctions and use of thrombolytic
      therapy did not disclose importance of Q waves on mortality. CONCLUSION: The
      electrocardiographic presence of Q waves is associated with increased mortality
      during the initial 30 days after a myocardial infarction, but has no influence
      thereafter.

PMID- 11469215
TI  - Serum Cyfra 21-1 as a co-variable in future NSCLC chemotherapy trials.

PMID- 11469218
TI  - On the conservation of protein sequences in evolution.

PMID- 11469219
TI  - [Mexican Association of Gastroenterology Annual Congress. December 2-7, 2000.
      Mazatlan, Sinaloa, Mexico. Abstracts].

PMID- 11469220
TI  - [Synchronous neoplasias in colorectal cancer].

PMID- 11469222
TI  - Turbine 2000. Proceedings of the International Symposium on Heat Transfer in Gas
      Turbine Systems. August 13-18, 2000. Cesme, Ismir, Turkey.

PMID- 11469221
TI  - Computerized 3D-reconstructions of the ligaments of the lateral aspect of ankle
      and subtalar joints.
AB  - 3D-reconstruction images of the structures of lateral aspect of the ankle and
      subtalar joints were produced using plastination to make equidistant serial
      sections of 1.2 mm in thickness. A SGI workstation was employed to reconstruct
      the structures of the ligaments of the lateral aspect of ankle and subtalar
      joints in three dimensions. Reconstructed structures were displayed singly, in
      groups or as a whole, and these were rotated continuously at different velocities
      in 3D space. Different diameters and angles of the reconstructed structures could
      be measured easily. Improved results could be achieved with the use of a special
      sectional anatomical technique, i.e. contours + marching cubes algorithm.

PMID- 11469223
TI  - Quantitation of HCV RNA in liver of patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Liver HCV RNA has been quantitated in few studies and the
      feasibility and the role of this parameter in the evaluation of patients with
      chronic HCV hepatitis still warrant study. Our aim was to determine the
      concentrations of HCV RNA in the liver of chronic HCV patients and to correlate
      the results with serum viral load. We also studied the relation of levels of HCV
      RNA in the liver with serum aminotransferases levels and with the presence of
      cirrhosis. METHODS: Twenty patients (14 males, aged 28 to 61 years) were studied.
      Twelve were infected by HCV type 1, six by type 3 and one by type 5. Percutaneous
      liver biopsy samples were obtained from 14 patients, and the remainder from liver
      explant in patients undergoing OLT. Twelve had chronic hepatitis and eight
      cirrhosis. HCV RNA levels were determined by bDNA. RESULTS: HCV RNA levels below
      the detection limit were found in one liver and in five serum samples. HCV RNA
      (mean +/- SD) was 2.1 x 10(8) +/- 2.2 x 10(8) Eq/gm in the liver and 94 x 10(5)
      +/- 93 x 10(5) Eq/mL in serum, with a significant correlation between these
      values (r = 0.89; P < 0.0001). Serum HCV RNA levels were significantly lower (P =
      0.001) in cirrhotic than in chronic hepatitis patients, while the groups did not
      differ in liver HCV RNA levels. No correlation was observed between liver or
      serum HCV RNA and serum ALT or AST. CONCLUSIONS: Quantitation of HCV RNA is
      possible even in small liver samples. Although average levels are more than one
      log higher than those observed in serum, hepatic concentrations correlate with
      those observed in serum. The application of this technology to monitoring
      antiviral therapy and understanding the pathogenesis of the disease remains to be
      determined.

PMID- 11469224
TI  - Fatal evolution of systemic lupus erythematosus associated with Crohn's disease.
AB  - The authors describe the case of a young Brazilian woman who was treated of
      ileocolonic Crohn's disease sparing rectum, as confirmed by colonoscopy and
      histopathological examination. After a 4-year course of sulfasalazine treatment,
      she presented with skin facial lesions in vespertilio, fever, arthralgias and
      high titers of anti-ANA and LE cells. A sulfasalazine-induced lupus syndrome was
      diagnosed, because after sulfasalazine withdrawal and a short course of
      prednisone, the clinical symptoms disappeared and the laboratory tests returned
      to normal. Mesalazine 3 g/day was started and the patient remained well for the
      next 3 years, when she was again admitted with fever, weakness, arthralgias,
      diplopy, strabismus and hypoaesthesia in both hands and feet, microhematuria,
      haematic casts, hypocomplementemia and high titers of autoimmune antibodies. A
      diagnosis of associated systemic lupus erythematosus was made. Although a
      pulsotherapy with methylprednisolone was started, no improvement was noticed. A
      cyclophosphamide trial was tried and again no positive results occurred. The
      patient evolved to severe clinical manifestations of general vasculitis affecting
      the central and peripheral nervous system and lungs, having a fatal evolution
      after 2 weeks. Although uncommon, the association of both disease may occur, and
      the authors call attention to this possibility, making a brief review of
      literature.

PMID- 11469225
TI  - Royal Army Medical Corps, 3rd Corps Medical Society. Treatment of wounds from
      fire trench to field ambulance. 1916.

PMID- 11469226
TI  - ADAHF reduces HIV screening frequency for dentists.

PMID- 11469227
TI  - SYBR green I used to evaluate the nuclei number of fungal mycelia.

PMID- 11469228
TI  - Comments on "Channel surfing" column.

PMID- 11469230
TI  - GASTRO 2001 annual scientific meeting. 5-8 April 2001. Abstracts.

PMID- 11469229
TI  - [Relation of some nutritional supplements and physical performance].
AB  - Many athletes and active people have consumed a large variety of supplements in
      order to get a good shape or a better performance in competitions. Due to this,
      several studies have been carried out to determine if these supplements are in
      fact ergogenic aids. Creatine seems to be related to the performance enhance in
      high intensity intermittent exercises. Carnitine might probably improve the
      aerobic capacity by stimulating lipid oxidation on muscle cells during long term
      exercise. Bicarbonate is thought to increase blood pH delaying the onset of
      peripheral fatigue in high intensity exercises of short duration and strength
      training. Some other supplements like branched-chain amino acids and chromium are
      also involved in body composition changes as a gain of fat free mass and loss of
      fat mass. The effects caused by these supplements during physical activity have
      not been fully described in literature yet as well as their side effects.

PMID- 11469231
TI  - Estimating log models: to transform or not to transform?
AB  - Health economists often use log models to deal with skewed outcomes, such as
      health utilization or health expenditures. The literature provides a number of
      alternative estimation approaches for log models, including ordinary least
      squares on ln(y) and generalized linear models. This study examines how well the
      alternative estimators behave econometrically in terms of bias and precision when
      the data are skewed or have other common data problems (heteroscedasticity, heavy
      tails, etc.). No single alternative is best under all conditions examined. The
      paper provides a straightforward algorithm for choosing among the alternative
      estimators. Even if the estimators considered are consistent, there can be major
      losses in precision from selecting a less appropriate estimator.

PMID- 11469232
TI  - 11th International Symposium on Amyotrophic Lateral Sclerosis and other Motor
      Neuron Disorders. Arhus, Denmark, 4-6 December 2000. Abstracts.

PMID- 11469234
TI  - Oral amiodarone and atrial fibrillation.

PMID- 11469235
TI  - Oral amiodarone and atrial fibrillation.

PMID- 11469236
TI  - Oral amiodarone and atrial fibrillation.

PMID- 11469237
TI  - Renal failure after bone marrow transplantation.

PMID- 11469238
TI  - Occult ectopic adrenocorticotropic hormone syndrome.

PMID- 11469239
TI  - Anticoagulation in atrial fibrillation.

PMID- 11469240
TI  - Thyroid dysfunction and chronic fatigue.

PMID- 11469241
TI  - Culturing of stool samples from hospital inpatients.

PMID- 11469242
TI  - Culturing of stool samples from hospital inpatients.

PMID- 11469243
TI  - Culturing of stool samples from hospital inpatients.

PMID- 11469244
TI  - Blood-pressure-lowering treatment.

PMID- 11469245
TI  - Hepatitis B virus subtypes and lamivudine resistance.

PMID- 11469246
TI  - Radicalism in treatment of lung cancer.

PMID- 11469247
TI  - Radicalism in treatment of lung cancer.

PMID- 11469248
TI  - Patients' dying wishes.

PMID- 11469249
TI  - Infection and cancer.

PMID- 11469250
TI  - Infection and cancer.

PMID- 11469251
TI  - 14th International Congress of Developmental Biology. July 8-12, 2001. Kyoto,
      Japan. Abstracts.

PMID- 11469252
TI  - [ Nodulation of certain legumes of the genus Crotalaria by the new species
      Methylobacterium].
AB  - We studied a collection of 126 rhizobial isolates from eight species of
      Crotalaria (C. comosa, C. glaucoides, C. goreensis, C. hyssopifolia, C.
      lathyroides, C. perrottetii, C. podocarpa, and C. retusa) growing in Senegal.
      Nodulation and nitrogen-fixation tests on nine Crotalaria species revealed two
      specificity groups within the genus Crotalaria. Group I consists of plants solely
      nodulated by very specific fast-growing strains. Group II plants are nodulated by
      slow-growing strains similar to promiscuous Bradyrhizobium spp. strains already
      reported to nodulate many tropical legumes. SDS-PAGE studies showed that slow
      growing strains grouped with Bradyrhizobium while fast-growing strains
      constituted a homogeneous group distinct from all known rhizobia. Amplified
      ribosomal DNA restriction analysis (ARDRA) of 10 representative strains of this
      group using four restriction enzymes showed a single pattern for each enzyme
      confirming the high homogeneity of group I. The 16S rDNA sequence analysis
      revealed that this specific group belonged to the genus Methylobacterium, thus
      constituting a new branch of nodulating bacteria.

PMID- 11469253
TI  - [IRepeat sequences of genomes of Rhizobium and Sinorhizobium meliloti: a
      comparative analysis].
AB  - Amongst prokaryotic genomes, those of nitrogen-fixing members of the Rhizobiaceae
      family are relatively large (6-9 Mb), often include mega-plasmids of 1.5-2 Mb,
      and contain numerous families of repeated DNA sequences. Although most essential
      nodulation and nitrogen fixation genes are well characterized, these represent
      only a small fraction of the DNA content. Little is known about the detailed
      structure of rhizobial genomes. With the development of sequencing techniques and
      new bio-informatic tools such studies become possible, however. Using the 2275
      shotgun sequences of ANU265 (a derivative of NGR234 cured of pNGR234a), we have
      identified numerous families of repeats. Amongst these, the 58-bp-long NGRREP-4
      represents the third most abundant DNA sequence after the RIME1 and RIME2
      repeats, all of which are also found in Sinorhizobium meliloti. Surprisingly,
      studies on the distribution of these elements showed that in proportion to its
      size, the chromosome of NGR234 carries many more RIME modules than pNGR234a or
      pNGR234b. Together with the presence in NGR234 and S. meliloti 1021 of an
      insertion sequence (IS) element more conserved than essential nodulation and
      nitrogen fixation genes, these results give new insights into the origin and
      evolution of rhizobial genomes.

PMID- 11469254
TI  - [Effects of inoculation with Rhizobium leguminosarum biovar trifolii on wheat
      cultivated in clover crop rotation agricultural soil in Morocco].
AB  - One hundred strains of Rhizobium leguminosarum bv. trifolii were isolated from
      roots of wheat cultivated in rotation with clover in two different regions of
      Morocco. The isolates were first screened for their effect on the growth of the
      cultivar Rihane of wheat cultivated in an agricultural soil under greenhouse
      conditions. After 5 weeks of growth, 14 strains stimulating the fresh or dry
      matter yield of shoots were selected and used in a second pot inoculation trial
      performed with two different agricultural soils. The results show that the
      strains behaved differently according to the soil used. In the loamy sand Rabat,
      strain IAT 168 behaved potentially like a plant growth promoting rhizobacteria
      (PGPR), as indicated by the 24% increases (P < 0.1) observed in wheat shoot dry
      matter and grain yields. In the silty clay Merchouch, no PGPR activity was
      observed, and 6 strains showed a significant deleterious effect on yields. These
      observations suggest that it is very important in a crop rotation system to
      choose a R. leguminosarum bv. trifolii strain that is effective with clover and
      shows PGPR activity with wheat to avoid deleterious effects on wheat yields.

PMID- 11469255
TI  - The latent tuberculosis bacillus (I'll let you know if I ever meet one).

PMID- 11469256
TI  - The contribution of ethnicity to Mycobacterium tuberculosis strain clustering.
AB  - OBJECTIVE: Descriptive study of molecular epidemiologic patterns of tuberculosis
      cases among ethnic minorities in Houston, Texas. DESIGN: Population-based,
      prospective, active surveillance, and molecular epidemiology study. PATIENTS:
      Tuberculosis cases reported to the City of Houston Tuberculosis Control Office
      between October 1995 and September 1998. RESULTS: During the study period, 1,139
      culture-positive patients were enrolled for whom isolates of their culture
      specimen were available. Of these, 910 were part of an ethnic minority. Molecular
      characterization identified 689 of 1,139 isolates to be clonally related. Factors
      significantly associated with tuberculosis strain clustering in a multivariable
      logistic regression analysis were: birth in the United States, a history of
      homelessness, infection with the human immunodeficiency virus (HIV), pulmonary
      disease, infection with a tuberculosis strain from principal genetic group 1 or
      3, living in a residence with five or more persons present, and use of public
      transportation more than once weekly. Asian ethnicity and increasing age were
      associated with decreased odds of clustering. CONCLUSIONS: Ethnicity was not a
      significant covariate for strain clustering after adjustments for factors related
      to socio-economic status.

PMID- 11469257
TI  - Communications to the 5th annual conference of the European College of Sport
      Science. Jyvaskyla, Finland, 19-23 July 2000.

PMID- 11469258
TI  - Pulmonary insulin administration using the AERx system: physiological and
      physicochemical factors influencing insulin effectiveness in healthy fasting
      subjects.
AB  - BACKGROUND: Orally inhaled insulin may provide a convenient and effective therapy
      for prandial glucose control in patients with diabetes. This study evaluated the
      influence of formulation pH and concentration and different respiratory maneuvers
      on pharmacokinetic and pharmacodynamic properties of inhaled insulin. METHODS:
      Three, open-label crossover studies in a total of 23 healthy subjects were
      conducted in which the safety, pharmacokinetics, and pharmacodynamics of insulin
      inhalation were compared to subcutaneous (SC) injection into the abdomen of
      commercially available regular insulin. A novel, aerosol generating system (AERx
      Diabetes Management System, Aradigm Corporation, Hayward, CA) was used to deliver
      aqueous insulin bolus aerosols to the lower respiratory tract from formulations
      at pH 3.5 or 7.4 and concentrations of U250 (250 U/mL) or U500 (500 U/mL).
      RESULTS: Time to maximum insulin concentration in serum (Tmax) after SC dosing
      occurred approximately 50-60 minutes with the time to minimum plasma glucose
      concentration (i.e., maximum hypoglycemic effect), (TGmin), occurring later, at
      around 100-120 minutes. In contrast, pulmonary delivery led to a significantly
      earlier Tmax (7-20 minutes) and TGmin (60-70 minutes), parameters that were shown
      to be largely unaffected by changing the pH or concentration of the insulin.
      However, investigation of changes in inhaled volume (achieved by different
      programming of the AERx system) for administration of the same sized aerosol
      bolus revealed significant effects. Significantly slower absorption and time to
      peak hypoglycemic activity occurred when aerosol delivery of insulin occurred
      during a shallow (approximately 40% vital capacity) as opposed to a deep
      (approximately 80% vital capacity) inspiration. In addition, it was shown that
      serum concentration of insulin increased immediately after a series of forced
      expiraratory maneuvers 30 minutes after inhaled delivery. CONCLUSIONS: Pulmonary
      delivery of aqueous bolus aerosols of insulin in healthy subjects resulted in
      rapid absorption with an associated hypoglycemic effect quicker than is achieved
      after subcutaneous dosing of regular insulin. Inhaled insulin pharmacokinetics
      and pharmacodynamics were independent of formulation variables (pH,
      concentration) but affected by certain respiratory maneuvers.

PMID- 11469259
TI  - Effect of acetaminophen on the accuracy of glucose measurements obtained with the
      GlucoWatch biographer.
AB  - BACKGROUND: Improved glycemic control significantly reduces long-term
      microvascular complications of diabetes mellitus associated with chronic
      hyperglycemia. The GlucoWatch biographer is designed to facilitate intensive
      diabetes management by providing automatic, frequent, and noninvasive glucose
      readings up to three times per hour for as long as 12 hours. METHODS: The device
      extracts glucose through intact skin using reverse iontophoresis and measures the
      extracted glucose with an electrochemical biosensor. A clinical trial was
      performed to assess the effect of acetaminophen, a potential interference for
      traditional blood glucose meters, on the accuracy of the GlucoWatch biographer in
      adult subjects with diabetes (n = 18). One thousand milligram doses of
      acetaminophen were administered to subjects in two groups: one to achieve Cmax
      (peak acetominophen concentration) at the time of biographer calibration and the
      other to achieve Cmax during the measurement period. The biographer readings were
      compared to serial fingerstick blood glucose measurements. RESULTS: Time profiles
      over 9 hours show close tracking of the biographer glucose results with
      fingerstick blood glucose measurements for all groups. The mean difference
      between the two measurements is between 8 and 12 mg/dL for all groups. The mean
      absolute value of the relative difference is less than 20%, and more than 93% of
      the points were in the clinically acceptable (A+B) region of the Clarke Error
      Grid. No statistically significant differences were found for any accuracy
      measurement across all groups. CONCLUSIONS: The GlucoWatch Biographer provides
      frequent measurements of glucose over a 12-hour period with high accuracy. No
      effect of therapeutic dosage of acetaminophen on the accuracy of the glucose
      readings was found.

PMID- 11469260
TI  - Glucose monitoring by reverse iontophoresis.

PMID- 11469261
TI  - Noninvasive glucose measurement by monitoring of scattering coefficient during
      oral glucose tolerance tests. Non-Invasive Task Force.
AB  - BACKGROUND: Continuous glucose monitoring by means of optical glucose sensors
      would allow patients with diabetes to check their metabolic control to their
      convenience. In an earlier study, we showed that noninvasive glucose monitoring
      is feasible for rapid changes in blood glucose by means of measuring the
      scattering coefficient of human skin. In this study, we investigated whether also
      slower changes in blood glucose, this time induced by an oral glucose load, can
      also be monitored by this approach. METHODS: Five healthy subjects and 13
      patients with type 2 diabetes have been given a 75-g oral glucose load. Portable
      noninvasive systems were used to measure the skin tissue scattering coefficient.
      For this purpose, two optical sensor heads were attached directly to the skin of
      each volunteer. Light was applied to the skin and the reflected light intensity
      was registered. RESULTS: In 8 of 10 measurements, correlation of changes in
      scattering coefficient with changes in glycemia was acceptable. In 19 of 26
      measurements (73%) of patients with type 2 diabetes the observed changes in the
      scattering coefficient also correlated in acceptable manner. The accordance
      between the simultaneous measurements of the two sensor heads was acceptable in
      13 of 18 volunteers and patients studied. There were virtually no differences in
      the quality of the measurements between healthy volunteers and patients with
      diabetes. CONCLUSIONS: This study shows that also slow changes in blood glucose
      induced by an oral glucose load can be monitored by registration of scattering
      coefficient changes. It remains to be elucidated why this has not been possible
      in all experiments.

PMID- 11469262
TI  - FreeStyle: a small-volume electrochemical glucose sensor for home blood glucose
      testing.
AB  - FreeStyle accurately measures the concentration of glucose in a 300-nL volume of
      capillary blood obtained with significantly reduced pain from the forearm where
      the density of capillaries is much lower than in the fingertips. The readings are
      independent of temperature, of altitude (O2 pressure) and of hematocrit in the 0%
      60% range. At their physiological levels, none of the often interfering
      constituents of blood affect the readings.

PMID- 11469263
TI  - Glucose meters: now what?

PMID- 11469264
TI  - Multisite evaluation of a new diabetes self-test for glucose and glycated protein
      (fructosamine).
AB  - BACKGROUND: In diabetes management, the true average blood glucose is best
      obtained using glycated protein tests that give the average blood glucose over a
      previous time window of either weeks (fructosamine tests) or months (glycated
      hemoglobin tests). Until now, glycated protein tests have only been available as
      laboratory tests and have therefore been underutilized in diabetes management.
      Recently, a fructosamine self-test for use by diabetes patients at home was
      cleared for marketing by the U.S. Food and Drug Administration (FDA). We have
      studied the performance of this test in three geographically distinct diabetes
      clinics to confirm the performance and accuracy of both glucose and fructosamine
      testing with this device. This new self-testing system has the potential to
      improve glycemic control dramatically in patients with diabetes, including those
      patients with type 2 diabetes using oral drug therapy. METHODS: Three
      geographically different sites (San Diego, CA, Tallahassee, FL, and Minneapolis,
      MN) were selected for the study. Sixty male and 56 female adult patients, with
      both type 1 (59) and type 2 (57) diabetes, were selected for participation in the
      study (total patients = 116). Fingerstick puncture capillary blood glucose was
      tested using the YSI Model 1500 and the Duet Glucose test. A fingerstick puncture
      capillary blood test was also tested with the Duet GlucoProtein (fructosamine)
      test strip in duplicate. For fructosamine comparison, a venipuncture blood sample
      of ethylene diaminetetraacetic acid (EDTA) plasma was collected and tested using
      the Roche Unimate laboratory test. RESULTS: The glucose test gave excellent
      correlation to the reference laboratory method (r = 0.98) and the GlucoProtein
      test gave a correlation of 0.72 compared to the laboratory method. The bias of
      both tests compared to the laboratory tests was 10% or less at all
      concentrations. Error grid analysis of the glucose test showed that 97.5% of test
      results were in the accurate zone and 2.5% were in the clinically neutral or
      benign errors zone. Analysis of fructosamine test results using a two-by-two grid
      yielded sensitivity of 100%, specificity of 92% and accuracy of 94%. CONCLUSIONS:
      The Duet Glucose Control System is accurate for both measuring glucose and
      GlucoProtein (fructosamine) using a fingerstick blood sample. This new testing
      system has the potential to provide useful information to both healthcare
      specialists in their office and also to patients at home to help them achieve
      better long-term glucose control and avoid the potential acute and chronic
      complications of diabetes.

PMID- 11469265
TI  - Measuring fructosamine at home.

PMID- 11469266
TI  - Potato-lactulose breath hydrogen testing as a function of gastric motility in
      diabetes mellitus.
AB  - OBJECTIVE: Scintigraphic determination of gastric emptying is the current
      standard for the assessment of gastric motility and the diagnosis of diabetic
      gastroparesis. However, such studies are expensive, inconvenient, and involve
      exposure to radiation. Because the time course of breath hydrogen (H2) excretion
      after ingestion of lactulose correlates with upper gastrointestinal transit time,
      we hypothesized that patients with diabetic gastroparesis would exhibit prolonged
      breath H2 excretion after ingestion of a test meal containing complex
      carbohydrate and lactulose compared to subjects without diabetes and subjects
      with diabetes but without gastroparesis. RESEARCH DESIGN AND METHODS: Ten healthy
      subjects without diabetes, 10 subjects with diabetes but without gastroparesis
      (gastric emptying T1/2,T1/2 < 90 minutes), and 10 subjects with diabetes and
      previously diagnosed gastroparesis (T1/2 > 90 minutes) were admitted for a single
      24-hour study. Gastric motility agents were withheld 24 hours prior to the study.
      Euglycemia was established and maintained overnight in subjects with diabetes
      with continuous intravenous insulin infusion. At 6:00 AM, all subjects ingested a
      breakfast containing 100 g of cooked potato starch and 20 g lactulose. Breath H2
      excretion was monitored at baseline and every 30 minutes for 12 hours after
      ingestion of the test meal. RESULTS: Twelve hours after ingestion of the test
      meal, raw and baseline adjusted breath H2 excretion was significantly elevated in
      the gastroparesis group compared to the unaffected group with diabetes and the
      group without diabetes (p < 0.001). The baseline and 12-hour data points were
      adequate to discriminate between normal and delayed gastric emptying.
      CONCLUSIONS: We conclude that patients with previously diagnosed gastroparesis
      exhibit prolonged breath H2 excretion after ingestion of a test meal. This test
      may prove to be a safe, reliable, and affordable outpatient screening test for
      diabetic gastroparesis.

PMID- 11469267
TI  - Using DNA chips to unravel the genetics of type 1 diabetes.
AB  - Thousands of genes are currently being discovered by sequencing the human genome.
      Of these, hundreds if not thousands fall into regions of the genome identified by
      genetic studies as linked to the development of type 1 diabetes. Inheritance
      patterns for these regions suggest that diabetes results from the combinatorial
      interaction of susceptibility loci. The study of such complex events will require
      technologies that can simultaneously evaluate expression profiles and allelic
      differences for all these genes in order to dissect the mechanisms responsible
      for the development of disease. We will argue that DNA microarrays are the
      natural vehicle for the exploration of diabetes-related gene clusters, and the
      application of these arrays to understanding diabetes is discussed.

PMID- 11469268
TI  - Metformin: intrinsic vasculoprotective properties.

PMID- 11469269
TI  - Antidiabetic drugs and the vascular system.

PMID- 11469270
TI  - Safety of drugs commonly used to treat hypertension, dyslipidemia, and Type 2
      diabetes (the metabolic syndrome): part 2.
AB  - It is becoming increasingly acknowledged that people with Type 2 Diabetes
      represent what can be termed "an enriched population": a group that has the
      greatest risk of morbidity and mortality from cardiovascular diseases such as
      myocardial infarcts and strokes. Due to the tremendous toll, both human and
      financial, that these cardiovascular diseases result in, major efforts are being
      put forth to decrease their occurrence. It is clear that success in this endeavor
      is optimized by achieving target levels of glucose, blood pressure, and
      cholesterol. Analysis of the individual drugs used to treat these comorbidities
      of the cardiovascular dysmetabolic syndrome has brought an understanding that
      frequently monotherapy is ineffective, and a clear appraisal of the benefits of
      available pharmaceuticals can result in a successful decision about which agents
      to include in regimens of combination therapy. This success translates into
      ultimately reducing the untimely death and disability that is unfortunately all
      too common among the people with these illnesses. As diabetes continues to be
      increasing alarmingly among all segments of the population, there is an urgency
      for this need. The knowledge is present; only the application is not.

PMID- 11469271
TI  - Screening for diabetic retinopathy by digital imaging photography and technician
      ophthalmoscopy.

PMID- 11469272
TI  - Rezulin to be withdrawn from the market.

PMID- 11469273
TI  - Warner-Lambert voluntarily withdraws Rezulin.

PMID- 11469274
TI  - Actos (pioglitazone HCL) provides a safe, effective alternative for patients
      formerly taking Rezulin.

PMID- 11469275
TI  - Avandia, a leading alternative for Rezulin patients, prescribed to more than
      700,000 patients.

PMID- 11469276
TI  - User reviews of AIDA online (http://www.shodor.org/aida): a Web-based interactive
      educational diabetes simulator.

PMID- 11469277
TI  - [XXXIV National Congress of the Spanish Society of Pneumology and Thoracic
      Surgery. A Coruna, 9-12 June 2001. Abstracts].

PMID- 11469278
TI  - Fatigue and Cancer. 2nd International Symposium. Cologne, Germany, 16-17 February
      2001. Abstracts.

PMID- 11469279
TI  - The management of fever and petechiae: collaborative studies are needed.

PMID- 11469280
TI  - Methodology for assessing patterns of interstitial pneumonia in children.

PMID- 11469281
TI  - Medication errors are NOT uncommon.

PMID- 11469282
TI  - Do autism spectrum disorders differ from each other and from non-spectrum
      disorders on emotion recognition tests?
AB  - We tested whether dimensional measures of empathic ability, theory of mind, and
      intelligence would differentiate autism spectrum disorders from each other and
      from non-spectrum disorders. Tests were administered to children with a diagnosis
      of Autistic Disorder (AutD; n = 20), Asperger's Disorder (AspD; n = 28),
      Attention Deficit/Hyperactivity Disorder (Inattentive Type) (ADHD; n = 35),
      Mental Retardation (Mild) (MR; n = 34), Anxiety Disorder (AnxD; n = 14), or No
      Psychological Disorder (NPD; n = 36). Results showed that empathic ability
      discriminated among groups on the autism spectrum (AutD < AspD < NPD). Because
      empathic ability is not independent of intelligence (AutD < AspD < NPD on
      intelligence; MR < ADHD < NPD on empathic ability), both dimensions are necessary
      to discriminate autism spectrum from non-spectrum disorders. When intelligence is
      covaried, empathic ability discriminated AutD, but not AspD, from other disorders
      (AutD < MR < ADHD < NPD = AnxD = AspD).

PMID- 11469283
TI  - MECP2 mutation screening in Swedish classical Rett syndrome females.
AB  - Rett syndrome (RS) is a neurodevelopmental disorder almost exclusively affecting
      females. We have studied the mutation spectrum of the responsible gene MECP2,
      encoding methyl-CpG-binding protein 2 (MeCP2), in 16 sporadic classical RS
      females from Sweden. In 13 of 16 patients (81%) we detected nonsense or missense
      mutations in the coding parts of MECP2. This mutation rate is in agreement with
      other reports (65-80%). In all, 12 different mutations and one polymorphism were
      found; three of the mutations have not been reported previously. The missense
      mutations were restricted to highly conserved regions of the gene. None of the
      mutations was detected in parents; thus, they had probably arisen de novo. In
      contrast, two normal variants, one intron deletion and one silent mutation, were
      seen singly only in two patients' mothers; neither has been reported previously.
      One patient showed two different mutations closely located, i.e. 802C > T (R268W)
      together with 808C > T (R270X). Another patient had a mutation in the stop codon
      1459T > C (X487R), leading to a gene product prolonged with 27 amino acids. In
      conclusion, our results indicate that the majority of Swedish RS patients (81%)
      have mutations in MECP2 that are sporadic cases with de novo mutations. Moreover,
      both missense and nonsense mutations occur, but in different parts of the gene,
      probably reflecting the function of the domains in MeCP2. This study has improved
      our ability to offer these families an early confirmation of Rett diagnoses.

PMID- 11469284
TI  - Cognitive performance and attachment patterns at four years of age in extremely
      low birth weight infants after early intervention.
AB  - This study aims at assessing the effects of an early occupational therapy
      intervention on the cognitive development and the development of attachment
      patterns in ELBW infants. The intervention, given weekly at home from six months
      to 12 months, aimed at supporting parent-child interaction and enhancing motor
      control and coordination. The study population consisted of 100 ELBW infants
      matched in pairs in accordance to their pre-perinatal risk scores and allocated
      successively to intervention or non-intervention groups. Cognitive development
      was assessed with the Bayley Scales at age two and with the WPPSI at age four.
      Attachment to primary caregiver was assessed with the Preschool Assessment of
      Attachment (PAA). Cognitive performance was within age norms in both groups at
      both ages. Intervention did not show any effect on cognitive performance at the
      age of two years. At the age of four years, cognitive level was overall, and most
      notably for verbal performance, higher in the intervention group than in the
      control group. There was an over-representation of the so-called atypical
      attachment patterns (those not fitting the normative A, B, or C categories) in
      the control group. The results are discussed in terms of finding more global ways
      to support the development of at risk pre-term children.

PMID- 11469285
TI  - Is clinic prevalence of ICD-10 hyperkinesis underestimated? Impact of increasing
      awareness by a questionnaire screen in an UK clinic.
AB  - Hyperactivity is common, but its diagnosis is still controversial, with two
      contending approaches: ADHD from DSM IV and hyperkinesis from ICD-10. The concept
      of ADHD predicts higher rates, but its use may lead to overmedication.
      Hyperkinesis usefully indicates medication, but clinics using it may detect many
      fewer cases, raising the possibility of underdiagnosis. It has never been shown
      whether this lower rate results from hyperkinesis' criteria, or to the differing
      methods used to detect hyperactivity in those centres that prefer it. We report a
      mirror study, examining rates of all types of hyperkinesis before and after the
      introduction of a preliminary screen (not originally intended to detect
      hyperkinesis). Its introduction resulted in an increase of detected hyperkinesis
      from 2% to 25% of the clinic sample with no change in diagnostic criteria. This
      was independent of any other change in the sample or clinic staff. We conclude
      that insensitive assessment may be responsible for low rates of diagnosis of ICD
      10 hyperkinesis in secondary care clinics.

PMID- 11469286
TI  - Multiple informants' report of emotional and behavioural problems in a nation
      wide sample of selective mute children and controls.
AB  - Emotional and behavioural problems and competencies in a nation-wide sample of
      referred selective mute children (SM) and matched non-referred controls, aged 4
      16 years, were assessed by the Child Behaviour Checklist, (CBCL), Teacher Report
      Form (TRF) and Youth Self Report (YSR) (1). Main issues addressed were the co
      variation of internalising and externalising problems reported across informants,
      whether there exists a pure externalising group of children with SM, and the
      nature of the internalising and externalising problems. The results show that the
      children with SM differed substantially from their peers in internalising
      problems as reported by the parents and the teachers. In contrast, the results on
      the YSR indicated an under-reporting of internalising problems. Externalising
      problems in SM were reported in a low to moderate degree by the parents only. No
      child with SM and pure externalising symptoms was found. The children with SM
      differed mostly from their peers on the withdrawn scale. On the item level, both
      the internalising and the externalising symptoms that best differentiated the
      children with SM from the controls support the notion of SM as an expression of
      social anxiety.

PMID- 11469287
TI  - Smoking in relation to psychosocial risk factors in adolescents.
AB  - OBJECTIVE: The study investigated which psychosocial factors distinguish
      adolescent smokers from non-smokers, and examined the most important factors
      correlated with smoking. METHOD: A cross-sectional survey carried out by means of
      a questionnaire which, in addition to items on family, school, healthy habits,
      drug abuse and suicidal behaviour, also included a scale of depression (Zung's
      SDS) and of self-esteem (Rosenberg's SES). Sample. Two thousand one hundred and
      eleven high school students aged from 17.0 to 18.11 (1,083 girls and 1,028 boys),
      of whom 221 girls and 239 boys were smokers. RESULTS: The smokers of both sexes
      differed significantly from the non-smokers in frequency of substance abuse,
      family dysfunction, suicidal ideation and suicide attempts, attitude towards the
      harmful effects of smoking, truancy from school, and lesser involvement in
      sports. With regard to smoking behaviour, the most important predictive factors
      for adolescents of both sexes proved to be substance abuse, truancy, suicide
      attempts, a lower estimate of the harmfulness of smoking, and infrequent
      engagement in sports. Among the girls, predictive factors were also sexual and
      physical abuse, and binge eating. CONCLUSIONS: Smoking behaviour in adolescence
      may be part of a pattern of problematic behaviour and may be linked to various
      psychopathological disturbances.

PMID- 11469288
TI  - Olanzapine in children and adolescents with chronic anorexia nervosa. A study of
      five cases.
AB  - Psychopathology in severely anorexic patients often seems to be of compulsive and
      delusional quality rendering therapeutic approaches extremely difficult. With
      conventional therapeutic regimes failing, administration of the novel
      antipsychotic olanzapine induced remarkable improvement in five cases reported
      here. Paranoid ideation concerning body image or weight gain decreased and
      sedative effects helped to reduce inner tensions and phobia with respect to food
      intake. Olanzapine, therefore, might represent an important therapeutic tool in
      anorexic patients who present the following characteristics: long-term history of
      anorexia nervosa mostly with several hospitalisations, missing perception of
      their severe state of illness, refusal of therapy, delusional quality of anorexic
      thinking, risk of discontinuation of therapy with life-threatening consequences.

PMID- 11469289
TI  - Emotional and behavioural problems in a sample of Finnish three-year-olds.
AB  - Behavioural and emotional problems in Finnish three-year-olds was studied using
      the Child Behavior Checklist for ages 2-3 as a standardised rating scale at well
      baby clinics in two cities in Finland. Altogether 374 questionnaires were
      analysed which is 71% of the target population. When compared with studies from
      other countries the mean scores and prevalences of preschool children's problem
      behaviours were rather similar. Boys were reported to be more destructive than
      girls. Parental education level, living in one-parent family and parental
      unemployment were associated with a higher level of problem behaviours. No
      significant differences were found in emotional or behavioural problems related
      to the child's day care. Co-sleeping with parents was associated with sleep
      problems.

PMID- 11469290
TI  - Pain reduction in untreated irreversible pulpitis using an intraosseous injection
      of Depo-Medrol.
AB  - The purpose of this prospective, double-blind, randomized study was to evaluate
      pain reduction using an intraosseous injection of slow-releasing
      methylprednisolone in teeth with irreversible pulpitis. Forty subjects presenting
      for emergency treatment completed the study. Each subject had a tooth with a
      clinical diagnosis of irreversible pulpitis with actively associated moderate to
      severe pain. After local anesthesia was attained, the subjects were randomly
      assigned to receive an intraosseous injection of either 1.0 ml of Depo-Medrol (40
      mg) or 1.0 ml of sterile saline (control). No endodontic therapy was begun at the
      initial appointment. The subjects received ibuprofen and Tylenol #3 and completed
      a 7-day questionnaire on pain, percussion pain, and analgesic medications taken
      each day. Over the 7-day observation period, the subjects who received the
      intraosseous injection of Depo-Medrol reported significantly (p < 0.05) less pain
      and percussion pain while taking significantly (p < 0.05) fewer pain medications.
      Clinically the intraosseous injection of Depo-Medrol could be used to temporarily
      alleviate the symptoms of irreversible pulpitis until definitive treatment can be
      rendered.

PMID- 11469291
TI  - A computerized method for mathematical description of three-dimensional root
      canal axis.
AB  - Knowledge of the three-dimensional (3D) morphology of root canals is important
      for successful endodontic treatment. The objective of the present study was to
      determine the 3D root canal axis mathematically. Two views (mesiodistal and
      buccolingual) of digitized images were taken from extracted natural human teeth.
      Geometric reconstruction to standardize projection geometry was conducted on
      images. Because 90-degree turn-around image pairs are Monge images of a given
      root canal, these Monge images were positioned using photogrammetric methods.
      Each well-ordered axis pair of a given root canal was put into a common
      coordinate system resulting in 3D polynomial function of the actual root canal.
      On the basis of the results gained using 10 samples evaluated with the Friedman
      statistical test, this description seems to be reproducible. The 3D
      representation of the root canal may help the clinicians in choosing the optimal
      instruments and shaping techniques. The root canal axis that is described by the
      3D function forms a basis for determination of curvature values and torsion
      values in each of the axis points. Evaluating these values may also yield a new
      type of classification.

PMID- 11469292
TI  - Effect of CO2, Nd:YAG, and ArF excimer lasers on dentin morphology and pulp
      chamber temperature: an in vitro study.
AB  - This study compared the effect of three laser systems: CO2 (10.600 nm), Nd:YAG
      (1.064 nm), and ArF excimer (193 nm) lasers on dentin hard tissue and on
      temperature increases of the pulp chamber. Sixty-six third molar teeth were used
      and randomly divided into three groups. A class I cavity was made to expose the
      dentin, and the pulp in the pulp chamber was removed via a hole bored in the
      cervical area. The pulp chamber was subsequently refilled with silicon grease,
      and a NiCr/NiSi thermocouple was inserted through the hole into the pulp chamber.
      The dentin surface was then lased for 30 s at the same settings (3 W, 2 mm spot
      size, 20 pps) with each laser. The average internal temperature increases were as
      follows: CO2, 37 degrees C; Nd: YAG, 28 degrees C; and ArF excimer, 1 degrees C.
      Scanning electron microscopy of the dentin in the occlusal cavity revealed
      extensive carbonization, isolated balls of recrystallized material, and the
      presence of smear layer at some dentinal tubule orifices for the CO2 and Nd:YAG
      lased teeth. Smear layer was also observed for the ArF excimer samples; however,
      they exhibited far less surface cavities than the others and seemed to undergo
      little morphological change on the dentin.

PMID- 11469293
TI  - Influence of mixing vehicle on dissociation of calcium hydroxide in solution.
AB  - The antimicrobial effects of aqueous preparations of calcium hydroxide have been
      demonstrated in the past. Calcium hydroxide, when dissolved in water, dissociates
      into hydroxide and calcium ions. The presence of hydroxide ions in a solution
      makes it antimicrobial. Recently it was shown that the use of glycerin as a
      mixing vehicle facilitates placement of calcium hydroxide in the root canals. The
      influence of nonaqueous mixing vehicles on the dissociation of calcium hydroxide
      is not clearly understood. In this study the conductivity of aqueous and
      nonaqueous solutions of calcium hydroxide was measured. The conductivity values
      for saturated solutions of calcium hydroxide in water was 7.3+/-3 mS/cm. The
      conductivity of calcium hydroxide in pure glycerin or propylene glycol was
      essentially zero. It was concluded that use of nonaqueous mixing vehicles may
      impede the effectiveness of calcium hydroxide as a root canal dressing.

PMID- 11469294
TI  - Antimicrobial substantivity of bovine root dentin exposed to different
      chlorhexidine delivery vehicles.
AB  - Root canal dentin acquires antimicrobial substantivity after exposure to
      chlorhexidine gluconate (CHX) for 1 wk. Therefore development of a vehicle for
      delivery of CHX as an intracanal medication is desirable. This in vitro study
      assessed the efficacy of two CHX delivery vehicles, a controlled-release device
      and a gel, to affect antimicrobial substantivity of bovine root dentin. Sixty
      bovine incisor root specimens were prepared with standardized length (10 mm) and
      canal diameter (3.3 mm), and coated externally with nail polish. Specimens were
      divided into four equal groups and their canals medicated for 7 days with either:
      (i) an experimental controlled-release device containing 25% CHX that was
      immersed in sterile saline; (ii) 2% CHX gel; or (iii) Ca(OH)2 paste. Sterile
      saline was used as the positive control. After medication, the canals of the
      specimens were inoculated with Enterococcus faecalis for 21 days. Root canal
      dentin samples ranging in depth from 0.1 to 0.45 mm were then obtained using
      sterile round burs of ascending diameter. Each dentin sample was placed in a
      separate test tube containing Brain Heart Infusion broth and incubated for 24 h.
      The optical density (OD) of the broth was then measured spectrophotometrically at
      540 nm. The positive control showed significantly higher mean OD values (one-way
      ANOVA and Tukey's Studentized Range Test; p < 0.001) than the three test groups.
      The CHX controlled-release device group showed significantly lower OD values than
      the Ca(OH)2 group; however only at dentin depths up to 0.2 mm. In contrast, the
      CHX gel group consistently showed significantly lower OD values than both the CHX
      controlled-release device and Ca(OH)2 groups. These results suggest that bovine
      root canals medicated with 2% CHX gel for 7 days acquire antimicrobial properties
      for at least 21 days.

PMID- 11469295
TI  - Resistance of a novel root canal sealer to bacterial ingress in vitro.
AB  - A dentin-bonding root canal sealer (ZUT) has been developed, consisting of an
      experimental glass ionomer cement (KT-308) and an antimicrobial silver-containing
      zeolite (0.2% by weight). This in vitro study evaluated the ability of ZUT used
      with or without gutta-percha, to resist bacterial ingress of Enterococcus
      faecalis over a period of 90 days. Canals of 80 single-rooted teeth were prepared
      with apical patency and filled as follows (n = 10): KT-308 alone; KT-308 with a
      single gutta-percha cone (SCGP); ZUT alone; ZUT with SCGP; AH26 alone; AH26 with
      SCGP; positive control-no root canal filling; and negative control-no root canal
      filling, with the apices of this group sealed with C&B Metabond cement. Teeth
      were coated with nail polish except for the apical 2 mm, and each tooth was
      sealed in a 4-ml glass vial, with an 18-gauge needle inserted through the vial
      cover and bonded into the pulp chamber with C&B Metabond cement. After
      sterilization with 2.5 Mrad gamma-radiation, Brain Heart Infusion broth with
      phenol red was injected into each vial. An inoculum of E. faecalis was pipetted
      through the needle into the pulp chamber every 5 days, and the broth was
      monitored daily for color change and turbidity. When change occurred, the broth
      was cultured for growth of E. faecalis. Kaplan-Meier survival analysis and the
      log-rank test revealed no significant differences among the three sealers used.
      The presence of gutta-percha, however, significantly improved resistance to
      bacterial ingress through obturated root canals (X, p < 0.05). Under the
      conditions of this study, the hypothesized advantage of ZUT (0.2% zeolite) was
      not demonstrated.

PMID- 11469296
TI  - A comparative scanning electron microscopic investigation of the efficacy of
      manual and automated instrumentation of root canals.
AB  - The cleaning effectiveness of automated and manual root canal instrumentation was
      investigated with the aid of a scanning electron microscope. Hand instrumentation
      was performed with K-Flexofiles used in a reaming working motion and according to
      the step-back technique and with Hedstrom files used in a filing motion.
      Automated preparation was performed with the KaVo-Endo Flash device featuring
      torque-limited rotation using K-Flexofiles, as well as with the mechanical
      ProFile system using rotary nickel-titanium instruments. Twelve teeth each with
      either straight or curved root canals were instrumented to size 40. After
      cracking the roots longitudinally (n = 120), the amount of debris and smear layer
      were quantified on the basis of a numerical evaluation scale (1 through 5).
      Comparison of manual instrumentation with the automated KaVo-Endo Flash resulted
      in an equivalent degree of canal cleaning. Complete cleanliness was not achieved
      by any of the techniques and devices investigated. Best instrumentation results,
      especially in curved canals, were obtained with rotary ProFile instruments.

PMID- 11469297
TI  - pH changes in root dentin after root canal dressing with gutta-percha points
      containing calcium hydroxide.
AB  - Alkalinizing action on root dentin was investigated by treating the enlarged root
      canals of a total of 120 extracted teeth for 24 h, 3 days, or 7 days with either
      gutta-percha points (size 40) containing calcium hydroxide or an equivalent
      quantity of aqueous calcium hydroxide suspension. After splitting the teeth
      longitudinally the pH of the dentin was determined using a pH microelectrode in
      small cavities at each of four set measuring points. The gutta-percha points were
      unable to alkalinize the root dentin over a period of 7 days. Clear, rapid, and
      prolonged alkalinization of the dentin extending through to the root surface was
      achieved, however, with the aqueous calcium hydroxide suspension.

PMID- 11469298
TI  - Effect of varying the depth of heat application on the adaptability of gutta
      percha during warm vertical compaction.
AB  - The purpose of this study was to compare the adaptability of gutta-percha after
      varying the depth of heat application in the obturation of a set of standard root
      canals. A split-tooth model was constructed using a human maxillary central
      incisor. The root canal was cleaned and shaped using a step-back preparation to a
      size #60 FlexOFile at the working length (WL). Five shallow depressions were
      produced on the root canal wall. Twenty obturations without sealer were performed
      for each technique (thermoplasticized injectable (TI), lateral condensation, and
      warm vertical compaction (WVC) with heat applications at 3, 4, 5, and 7 mm from
      the WL). After each obturation the model was separated and the mesial and distal
      sides of each obturation were examined and videotaped at x 32 magnification. The
      quality of the obturation was graded based on the replication to the WL,
      replication of the artificial depressions, surface adaptation, and homogenicity
      of the gutta-percha. The Kruskal-Wallis analysis and the Student-Newman-Keuls
      tests indicated that all the techniques were significantly different from each
      other (p < 0.05) except for the TI group versus the WVC group with the heat
      application to within 3 mm from the WL (p > 0.05). The TI technique was ranked
      best followed by the WVC with heat applications at 3, 4, 5, and 7 mm. The lateral
      condensation technique received the lowest ranking.

PMID- 11469299
TI  - Frequency of second mesiobuccal canals in maxillary molars as determined by use
      of an operating microscope: a clinical study.
AB  - Operating microscopes have recently been introduced to facilitate treatment of
      surgical and nonsurgical endodontic cases. The aim of this study was to determine
      in an in vivo clinical study if the use of an operating microscope would increase
      the number of second mesiobuccal canals located and obturated in maxillary first
      and second molars. Two hundred maxillary first and second molars treated with the
      aid of a microscope were evaluated. The number of second mesiobuccal canals that
      could be negotiated and obturated within 4 mm of the apex was recorded. Thirty
      percent of all maxillary molars had a negotiable second mesiobuccal canal.
      Evaluated separately, 33.1% of the maxillary first molars and 24.3% of the second
      molars had a negotiable second mesiobuccal canal. Results indicated that use of a
      surgical microscope did not increase the number of second mesiobuccal canals
      located, compared with those reports where access preparations were modified and
      the microscope was not used.

PMID- 11469300
TI  - Root canal morphology of human maxillary and mandibular third molars.
AB  - The anatomy of third molars has been described as unpredictable. However
      restorative, prosthetic, and orthodontic considerations often require endodontic
      treatment of third molars in order for them to be retained as functional
      components of the dental arch. The purpose of this study was to investigate and
      characterize the anatomy of maxillary and mandibular third molars. One hundred
      fifty maxillary and 150 mandibular extracted third molars were vacuum-injected
      with dye, decalcified, and made transparent. The anatomy of the root canal system
      was then recorded. Seventeen percent of mandibular molars had one root (40% of
      which contained two canals), 77% had two roots, 5% had three roots, and 1% had
      four roots. Teeth with two roots exhibited highly variable canal morphology,
      containing from one to six canals, including 2.2% that were "C-shaped." Fifteen
      percent of maxillary molars had one root, 32% had two roots, 45% had three roots,
      and 7% had four roots. Teeth with one root demonstrated the most unusual
      morphology, with the number of canals varying from one to six. An in vivo study
      of the canal morphology of treated third molars is suggested to provide the
      practitioner with an understanding of the clinical implications of third molar
      root anatomy.

PMID- 11469301
TI  - Charcot-Leyden crystals within a periapical lesion.
AB  - Transmission electron microscopy revealed the presence of Charcot-Leyden crystals
      within a periapical lesion, which was assessed histopathologically as consistent
      with a periapical granuloma that failed to resolve after conventional endodontic
      treatment. This paper presents the clinical, radiographic, histological, and
      ultrastructural findings of this case and discusses their potential clinical
      significance.

PMID- 11469302
TI  - Practices, outcomes and paradigms: factors causing a change in behavior.

PMID- 11469303
TI  - Quantitative evaluation of intact peripheral nerve structures after utilization
      of CO2 laser, electrocautery, and scalpel.
AB  - OBJECTIVE: This study aimed to evaluate quantitatively the integrity of nerve
      structures near CO2 laser incisions. BACKGROUND DATA: There are some hypotheses
      that try to explain the analgesia reported after CO2 laser surgery. One of them
      is based upon the observation of the destruction of nerve endings after use of
      this technique. METHODS: A comparative study was carried out using 25 animals
      (Rattus norvegicus) divided into five groups of 5 animals each. Standard
      incisions were carried on the dorsum of the tongue of each animal using the
      cautery (group 2), scalpel (group 3), CW CO2 laser (group 4), and SPS CO2 (group
      5); group I served as control. The animals were killed immediately after the
      experiment, and specimens were taken and routinely processed to wax. Three
      micrometer sections were cut and stained using S-100 protein antibody. The
      stained sections were analyzed under light microscopy using a calibrated
      graticule, and the number of intact nerves was counted in five standard areas
      around the incision. RESULTS: The results of this study showed that there were no
      statistically significant differences in the numbers of intact peripheral nerve
      structures in both laser groups and other groups. No statistically significant
      difference was found between nonoperated and scalpel groups. The number of intact
      peripheral structures in cautery wounds was significantly smaller than in non
      operated and scalpel wounds. CONCLUSIONS: Therefore, it is unlikely that
      immediate destruction of peripheral nerve structures is the cause of post
      operative analgesia following CO2 laser surgery.

PMID- 11469304
TI  - Removal of carious dentin by Er:YAG laser irradiation with and without carisolv.
AB  - OBJECTIVE: The purpose of this study was to investigate the effectiveness of
      caries removal by using an Er:YAG laser irradiation with and without Carisolv, in
      vitro. BACKGROUND DATA: Effective ablation of dental hard tissues using Er:YAG
      laser has been reported and its application to caries removal has been expected.
      METHODS: Five extracted human teeth were selected for Carisolv and burr
      treatment. One-half of the lesion was treated with the Carisolv and then removed.
      The other half was removed using burr treatment. Fifty teeth were subjected to
      Er:YAG laser treatment with and without Carisolv. First, Carisolv was applied on
      one-half of each carious lesions for 1 min and followed by the Er:YAG laser
      irradiation at 60-140 mJ, 2 Hz for another 1 min; the other half was treated with
      Er:YAG laser only. The cavity was carefully assessed by DIAGNOdent. Each lesion
      was photographed before and after treatment, and the treated cavity was observed
      by microscopy and with scanning electron microscope (SEM). RESULTS: Our results
      revealed that application of Carisolv followed by Er:YAG laser irradiation at 100
      140 mJ pulse energy effectively removed dentin caries. From the SEM study, it was
      found that the cavity surface treated with the laser revealed various patterns of
      microirregularity, often accompanied by microfissure propagation. There was also
      no smear layer. CONCLUSIONS: It was revealed that Er:YAG laser and Carisolv could
      provide an alternative technique for caries removal for conventional mechanical
      drilling and cutting.

PMID- 11469305
TI  - Laser use and research in gastroenterology, gynecology, and general surgery: a
      status report.
AB  - OBJECTIVE AND BACKGROUND DATA: Despite the burgeoning growth of laser
      applications in dermatology and plastic surgery, applications in other
      specialties have declined. Laser use in gastroenterology, general surgery, and
      gynecology was examined over the past 3 years. Future trends and opportunities
      are discussed. METHODS: The MEDLINE database was scanned for scholarly
      publications between January 1, 1997, and January 1, 2000, and the number of
      publications in these specialties was determined. A questionnaire was distributed
      to 362 general surgeons from the American Society for Laser Medicine and Surgery
      (ASLMS) to assess current use and future needs. These results were compared to
      the actual cases performed at a laser center over the same period. RESULTS: Of
      3,331 publications, 21 (0.6%) covered gastroenterology (GE), general surgery
      (GS), gynecology (GYN), or laparoscopy (LAP). Keyword citations were 2 GS, 3 GYN,
      7 GE, and 12 LAP. Questionnaire results and actual utilization were well
      correlated. CONCLUSIONS: Lasers are being used in these specialties despite slow
      development of novel uses. Opportunities exist for future applications.

PMID- 11469306
TI  - Study on acid resistance of human dental enamel and dentin irradiated by
      semiconductor laser with Ag(NH3)2F solution.
AB  - OBJECTIVE: The purpose of this study was to investigate the acquired acid
      resistance of human dental enamel and dentin treated by 38% diamine silver
      fluoride [Ag(NH3)2F] solution and semiconductor (diode) laser irradiation in
      vitro. BACKGROUND DATA: There have been no reports on the acid-resistant effect
      by combined use of fluoride and semiconductor laser. METHODS: Sixty crowns of
      extracted human molars were divided into two groups for enamel and dentin
      samples, and each group was subdivided into three subgroups of 10 each. Each
      subgroup of enamel and dentin samples served as a control; one was treated with
      Ag(NH3)2F and the other was treated with Ag(NH3)2F and semiconductor laser
      irradiation at 2 W for 30 sec. Then all samples were immersed in 5 ml of 0.1 M
      lactic acid (pH 4.8) at 37 degrees C for 24 h. The concentration of calcium ion
      (Ca2+) dissolved in the solution was measured by atomic absorption
      spectrophotometry, and the samples were observed by stereoscopy and scanning
      electron microscopy (SEM). RESULTS: In both enamel and dentin samples, dissolved
      Ca2+ concentration in Ag(NH3)2F- or Ag(NH3)2F- and laser-treated group was
      significantly decreased compared with that in the control (p < 0.01). SEM
      findings showed that numerous cubic particles ranging from 0.1 to 0.5 mcirom were
      observed only in the combined treated groups of both enamel and dentin samples.
      CONCLUSIONS: A significantly decreased solubility of human enamel and dentin was
      acquired after treatment by Ag(NH3)2F and semiconductor laser irradiation, which
      suggested that this combined use has the capability of a more efficient acid
      resistant effect on human dental hard tissues.

PMID- 11469307
TI  - Review of safety in endoscopic laser foraminoplasty for the management of back
      pain.
AB  - OBJECTIVE: The purpose of this study was to analyze the incidence and gravity of
      reported complications that arise in spinal surgery and assess the comparative
      safety, or otherwise, of endoscopic laser foraminoplasty (ELF). BACKGROUND DATA:
      Chemonucleolysis, decompression, discectomy, and fusion have long been cited as
      treatments for chronic low back pain. Over recent years newer, less invasive
      surgical techniques have become available, one such being ELF. Although minimally
      invasive, the beneficial outcome must be interpreted in relation to concerns
      regarding the safety of the procedure and its risks relative to those of other
      forms of spinal surgery. The Spinal Foundation, Rochdale has performed 958 ELFs
      and has collated a comprehensive database of the results of all these operations.
      These prospective records provided the basis for a comparison of the safety of
      ELF to that reported with other spinal surgical techniques. METHODS: A total of
      958 procedures have been performed on 716 patients. Complications that arose
      during the operation and the postoperative phase of 6 weeks following the
      procedure were elicited from patient records. These data were correlated and
      compared to a meta-analysis of randomized controlled clinical trial data of
      complications arising during and after conventional spinal surgery. The SPSS
      (statistical package for social sciences) and CIA (confidence interval analysis)
      statistical packages were used to draw conclusions regarding the safety of ELF.
      RESULTS: The cohort integrity of operation and outpatient review records at 6
      weeks after surgery was 100%. In 958 ELFs performed, 24 complications occurred in
      23 patients. There were 9 cases of discitis (1 infective, 8 aseptic) (0.9%), 1
      dural tear (0.1%), 1 deep wound infection (0.1%), 2 patients suffered a foot drop
      (1 transient) (0.2%), 1 myocardial infarction (0.1%), 1 erectile dysfunction
      (0.1%), and 1 patient who developed panic attacks post-operatively (0.1%). This
      amounts to an overall surgical complication rate of 1.6%. Magnetic resonance
      imaging (MRI) follow up of clinically symptomatic patients highlighted 8 residual
      disc herniations (0.8%). Meta-analysis of randomized controlled trials of
      conventional spinal surgery for adult onset degenerative disc disease and/or
      sciatic pain reported overall complication rates for fusion (11.8%),
      decompression (7.6%), discectomy (6.0%), and chemonucleolysis (9.6%).
      CONCLUSIONS: The complication rate of ELF is shown to be significantly lower than
      that reported following conventional spinal surgery (p < 0.01). From these
      results, we conclude that ELF as a treatment for chronic low back pain and
      sciatica presents less risk to a patient than conventional methods of spinal
      surgery.

PMID- 11469308
TI  - A study on acquired acid resistance of enamel and dentin irradiated by Er,Cr:YSGG
      laser.
AB  - OBJECTIVE: This investigation was performed to evaluate the acid resistance of
      lased enamel and dentin by Er,Cr:YSGG laser to artificial caries-like lesions by
      spectrophotometry, and the ultrastructure of lased areas was investigated by
      scanning electron microscopy (SEM) in vitro. BACKGROUND DATA: In recent years,
      many studies have been performed to evaluate the effects of Er,Cr:YSGG laser on
      dental hard tissues. However, there have been only a few studies to determine if
      this laser is suitable for caries preventive treatments. METHODS: An Er,Cr:YSGG
      laser was used to irradiate the enamel or dentin samples from 30 extracted human
      molars at 6 W (67.9 J/cm2) or 5 W (56.6 J/cm2) pulse energy, respectively, with
      or without water mist. Samples were subjected to 2 microl of 0.1 M lactic acid
      solution (pH 4.8) for 24 h at 36 degrees C. The parts per million (ppm) of
      calcium ion (Ca2+) dissolved in each solution was determined by atomic absorption
      spectrophotometery, and the morphological changes were investigated by SEM.
      RESULTS: The lowest mean Ca2+ ppm was recorded in the lased samples. SEM
      observation showed that the lased areas were melted and seemed to be thermally
      degenerated. After acid demineralization, the thermally degenerated enamel or
      dentin surfaces were almost unchanged. CONCLUSIONS: The results of this study
      suggested that Er,Cr:YSGG laser irradiation with and without water mist appears
      to be effective for increasing acid resistance.

PMID- 11469309
TI  - Laser literature watch.

PMID- 11469310
TI  - Structure and strategy in the associative false memory paradigm.
AB  - List-learning experiments can have several levels of structure: individual words,
      the gist (if any) of each list, and the task in which those lists are embedded.
      The usual presentation of the DRM associative paradigm (Deese, 1959; Roediger &
      McDermott, 1995) strongly encourages a focus on gist and produces a high rate of
      false recall of key words (FRK). The experiments reported here were designed to
      invite the use of memory strategies based on structures other than the gist and
      thus reduce FRK. The crucial condition of Experiment 1, short lists followed by
      rehearsal, encouraged a focus on individual words and produced a low rate of FRK.
      In Experiment 2, the lists were embedded in a guessing game, which virtually
      eliminated FRK. FRK was also low in Experiments 3a and 3b when participants
      engaged in a complex task involving the first letters of list words. The
      relevance of these findings to false memories in the DRM and the connection of
      false autobiographical memories is discussed.

PMID- 11469311
TI  - Prospective memory in dynamic environments: effects of load, delay, and
      phonological rehearsal.
AB  - A new paradigm was developed to examine prospective memory performance in a
      visual-spatial task that resembles some aspects of the work of air traffic
      controllers. Two experiments examined the role of workload (number of aeroplanes
      that participants directed), delay (between receipt of prospective instructions
      and execution), and phonological rehearsal. High workload increased prospective
      memory errors but increasing delay from 1-3 or 5 minutes had no effect. Shadowing
      aurally presented text reduced prospective memory performance, presumably because
      it prevented verbal rehearsal of the prospective instructions. However,
      performance on the foreground task of directing aeroplanes to routine
      destinations was affected only by workload and not by opportunity for rehearsal.
      Our results suggest that ability to maintain performance on a routine foreground
      task while performing a secondary task--perhaps analogous to conversation--does
      not predict ability to retrieve a prospective intention to deviate from the
      routine.

PMID- 11469312
TI  - Prospective remembering in younger and older adults: role of the prospective cue.
AB  - In these studies, adult age differences in event-based prospective memory were
      examined using an adapted version of G.O. Einstein and M.A. McDaniel's (1990)
      task. In Experiments 1-3, we varied prospective cue specificity by assigning a
      specific target word or an unspecified word drawn from a given taxonomic
      category. In Experiment 3, we manipulated cue typicality by presenting low or
      high typicality target words. Results yielded positive effects of cue specificity
      on prospective performance. Age effects occurred when high typicality target
      words served as prospective cues (Exps. 1 and 3), but younger and older adults
      performed comparably with moderate and low typicality words (Exps. 2 and 3).
      Hierarchical regression analyses indicated that age accounted for a small but
      significant amount of variance in prospective memory, although the contribution
      of age was substantially reduced after statistically controlling for recognition
      memory. Implications of these data for current views on prospective remembering
      are discussed.

PMID- 11469313
TI  - "It was never that bad": biased recall of grief and long-term adjustment to the
      death of a spouse.
AB  - At 6 months following the death of their spouse, 37 participants reported their
      grief-related symptoms and thoughts, and then, approximately 4.5 years later,
      they attempted to recall how they felt at the time of the 6-month report.
      Although participants were far less distressed at recall than initially, they
      recalled their 6-month grief rather accurately. Participants did however
      overestimate prior grief-related intrusive ideation. Participant's current level
      of grief predicted what they recalled slightly better than the actual initial
      grief. Conversely, what they recalled predicted current levels of grief across
      various measures. Participants whose grief diminished relatively little over time
      tended to overestimate prior grief more. The retrospective reappraisal that one's
      past grief was not severe may indicate effective coping.

PMID- 11469314
TI  - Tetracycline residues in meat and bone meals. Part 2: the effect of heat
      treatments on bound tetracycline residues.
AB  - The stability of bound tetracycline residues during heat treatments at 133
      degrees C and 100 degrees C for up to 45 min was investigated. An intermediate
      product from a rendering plant was mixed with bone splinters that contained bound
      tetracycline (TC) and chlortetracycline (CTC) residues. The mixture was heated in
      an autoclave at 133 degrees C for 20, 30 and 45 min and at 100 degrees C for 20
      and 30 min and subsequently dried at 103 degrees C for 4 h. Two different
      extraction procedures with hydrochloric acid were used, one with and one without
      the previous sedimentation of bone particles. Tetracycline concentrations were
      determined by HPLC analysis before and after the heat treatment. A complete
      destruction of tetracyclines during heat treatment at 133 degrees C could not be
      demonstrated, but there was a significant decrease of TC by about 50%. CTC was
      less resistant to the same temperature, which brought about a reduction of 90
      100%. Treatment at 100 degrees C did not bring about any reduction, except for
      CTC after extraction without sedimentation. The possible toxicological relevance
      of the findings is discussed. Further research has to be done on possible
      degradation products of the tetracycline derivatives.

PMID- 11469315
TI  - Estimation of chromium bioavailability from the diet by an in vitro method.
AB  - An in vitro method was used to study the dialysable fraction of chromium (Cr)
      from the diet which simulates human gastric and intestinal digestion. The
      percentage of dialysed Cr was used to assess the bioavailability. The duplicate
      diet approach was used to obtain ten different sets of samples each
      representative of the normal diet consumed in southern Spain. In each case
      triplicate analysis of Cr was carried out by electrothermal atomization-atomic
      absorption spectrometry in acid-mineralized samples. The Cr dietary intake ranged
      from 16 to 117 microg/day, and the dialysable Cr fraction ranged from 0.4% to
      1.6%. The Cr absorption was higher for low levels of daily dietary intake of Cr
      (< 40 microg) than for levels of 40-80 microg; for high levels (> 80 microg)
      there was an increase in the dialysable fraction. The energy and nutrient intake
      of these diets was also evaluated.

PMID- 11469316
TI  - Cadmium in caribou (Rangifer tarandus) kidneys: speciation, effects of
      preparation and toxicokinetics.
AB  - Caribou kidney is a major source of cadmium (Cd) in the traditional diets of many
      aboriginal communities in the Arctic. In order to characterize the risk of Cd
      exposure, we studied the speciation of Cd in caribou kidneys and how, it can be
      affected by food preparation. Cd in caribou kidneys was bound to metallothionein
      (MT) (40%) high molecular weight proteins (50-500 kDa) (30%) and existed as free
      ions (10%). There was no change in Cd concentrations after the samples were baked
      at 350 degrees C for 30 min but the MT level was significantly decreased. Food
      preparation also denatured the high molecular weight proteins, resulting in a
      significant increase of free Cd. The toxicokinetics of Cd in caribou kidney was
      studied using a rodent model. Four groups (n = 6) of adult Sprague-Dawley rats
      were fed with rat chow with the addition of one of the following: 10% veal kidney
      with 0 microg/g Cd, 10% veal kidney spiked with CdCl2 to make up to 66 microg Cd;
      10% caribou kidney containing 20 microg/g Cd and 10% caribou kidney containing 66
      microg/g Cd. After 14 days, Cd accumulation increased with dose but less than 1%
      of the dosed Cd accumulated in the liver and kidney of rats. The percentage of Cd
      accumulated in the liver was higher in the group fed with caribou kidney than
      that dosed with spiked veal kidney. Our results suggest that caribou kidney is a
      major source of Cd exposure among the Arctic populations but moderate consumption
      may be considered unavoidable.

PMID- 11469317
TI  - Pesticide residues in oranges from Valencia (Spain).
AB  - One hundred and fifty citrus samples from an agricultural co-operative of the
      Valencian Community (Spain) were analysed for pre- and post-harvest pesticide
      residues using high performance liquid chromatography and gas chromatography.
      Among the residues from post-harvest treatments, imazalil was detected in 112
      (74.7%) samples at a mean level of 1.2 mg/kg, thiabendazole in 21 (14.0%) samples
      at a mean level of 0.47 mg/kg and carbendazim in 5 (3.3%) samples at a mean level
      of 1.05 mg/kg. Among the residues from pre-harvest treatment, dicofol was
      detected in 28 (18.7%) samples at a mean level of .28 mg/kg chlorpyriphos in 19
      (12.7% samples at a mean level of 0.16 mg/kg and endosulfan in 11 (7.3%) at a
      mean level of 0.27 mg/kg. Most of the samples contained residues of various
      pesticides and six samples (4.0%) exceeded the European Union Maximum Residue
      Limit (MRL). The pesticides that surpassed the MRLs were chlorpyriphos in five
      samples and dicofol in one.

PMID- 11469318
TI  - Fenhexamid residues in grapes and wine.
AB  - The behaviour of the fungicide, fenhexamid, on grapes, and during wine-making, as
      well as its effect on the microflora of alcoholic and malolactic fermentation has
      been studied. After treatment, the residue on grapes decreased rapidly to one
      third of the initial level after the first week, while it remained constant
      during the following two weeks. At harvest, in the wine obtained by vinification
      without skins, the fungicide residue decreased on average by 49%, while in the
      wine obtained by vinification with skins, the decrease was on average 62%. The
      presence of this fungicide on grapes and in the wine did not affect alcoholic and
      malolactic fermentation, nor did fermentation cause any degradation of the
      fungicide. A simple and rapid gas chromatograhic method (GC-NPD) for the
      determination of fenhexamid residues in grapes, must and wine is described.

PMID- 11469319
TI  - Survey of Brazilian tomato products for alternariol, alternariol monomethyl
      ether, tenuazonic acid and cyclopiazonic acid.
AB  - Alternariol (AOH), alternariol monomethyl ether (AME) and tenuazonic acid (TEA)
      are secondary metabolites of Alternaria species. Cyclopiazonic acid (CPA) is
      produced by fungi belonging to the ubiquitous genera of Penicillium and
      Aspergillus and has been found in a wide range of foods. These toxins were
      searched for by liquid chromatography with diode-array detection in tomato
      products processed and sold in Brazil. Eighty samples of tomato products were
      examined (juice 11, pulp 22, puree 22, paste 24 and whole stewed tomato 1).
      Eleven brands sold nationwide were covered. TEA was found in seven samples of
      tomato pulp (39-111 ng/g) and four samples of tomato puree (29-76 ng/g). CPA was
      found in six samples of pulp (64-178 ng/g) and two samples of puree (36-117
      ng/g). Co-occurrence of TEA and CPA was found in two samples of puree and one of
      pulp. This is the first time that the presence of CPA has been reported in tomato
      products. Neither AME nor AOH were detected in the samples.

PMID- 11469320
TI  - A simple HPLC method for the determination of the mycotoxins ochratoxin A and B
      in blood serum of swine.
AB  - This paper presents a simple method for the determination of ochratoxins A (OTA)
      and B (OTB) in pig blood serum. The method includes serum acidification (pH <
      1.6) and precipitation of protein with 15% trichloroacetic acid, liquid
      partitioning with dichloromethane and fluorescence detection. The estimated
      detection limits were 0.1 ng OTA/ml and 0.2 ng OTB/ml. The mean recoveries from
      artificially contaminated samples (n = 6 replicates/mycotoxin) spiked at 0.3, 1
      and 3ng OTA and OTB/ml, respectively, were 86.8% (s.d. = 8.4) for OTA and 90.0%
      (s.d. = 9.8) for OTB. Forty-nine Romanian pig blood serum samples (94% of 52
      analysed) were found to be naturally contaminated with OTA in the range 0.1-13.4
      ng/ml. No sample was found positive for OTB. The method is technically simple,
      specific, cost effective, suitable for large sample throughput and requires small
      amount of sample and reagents. It fulfils the criteria for a routine method and
      could be a suitable toolfor surveying OTA in pig herds and in slaughtered pigs.

PMID- 11469321
TI  - Survey of the occurrence of aflatoxin M1 in dairy products marketed in Italy:
      second year of observation.
AB  - During 1996, 161 samples of milk, 92 samples of dry milk for infant formula and
      120 samples of yoghurt, were randomly collected in supermarkets and drug stores
      in four big Italian cities, and checked for aflatoxin M1 (AFM1) by immunoaffinity
      column extraction and HPLC. AFM1 was detected in 125 (78%) of milk samples
      (ranging from < 1 ng/l to 23.5 ng/l; mean level: 6.28 ng/l), in 49 (53%) of dry
      milk samples (ranging from <1 ng/l to 79.6 ng/kg; mean level: 32.2 ng/kg) and in
      73 (61%) of yoghurt samples (ranging from <1 ng/kg to 32.1 ng/kg; mean level:
      9.06 ng/kg). Altogether, only four samples of dry milk were over the legal limits
      established by the EC in 1999. It is concluded that during 1996, despite the
      widespread occurrence of AFM1, mean contamination levels in dairy products sold
      in Italy were not a serious human health hazard.

PMID- 11469322
TI  - Occurrence of ochratoxin A in Italian wines.
AB  - A total of 96 red wines and 15 white dessert wines produced mostly in the years
      1995-97 in 19 Italian regions were analysed for ochratoxin A (OTA). The amount of
      OTA ranged from < 1 to 3856 ng/l the median (mean) was found to be 90 (419) ng/l
      for the red wines and 8 (736) ng/l for the white dessert wines. Our survey shows
      that the geographic region of origin has a strong influence on OTA contamination,
      both for red and for dessert wines: in fact, wines produced in southern Italy
      were markedly more contaminated. The overall median (mean) OTA concentration in
      the red wines produced in the four Italian areas (northwest, northeast, centre
      and south) was 2 (11), 90 (81), 134 (295) and 1264 (1233) ng/l. The same trend
      was observed for the white dessert wines: OTA concentrations of over 1000 ng/l
      were found in four out of five samples from southern Italy (1185, 2454, 3477,
      3856 ng/l), while central and northern samples showed very low contamination. The
      contribution of wine to mean daily OTA intake can be considered negligible in the
      case of people drinking wine manufactured in northern and central Italy; this is
      not true if a medium drinker constantly consumes red wine produced in southern
      Italy in this case wine alone could supply the diet with an amount of OTA equal
      to or even above the tolerable daily intake of 5 ng/kg body weight recommended by
      the Scientific Committee on Food of the European Commission.

PMID- 11469323
TI  - Method for determining novolac glycidyl ether (NOGE) and its chlorohydrins in
      oily canned foods.
AB  - In order to be analysed, NOGE components with epoxy groups must be separated from
      polar food material to prevent losses through uncontrolled reactions. Samples are
      homogenized minimally and extracted into a phase of minimized polarity. The NOGE
      components are then separated from the oil by extraction into acetonitrile and
      analysed by RPLC with fluorescence detection. Hydrolysis of the epoxy, and
      chlorohydroxy functions to diols may help the analysis. Application and
      limitations of the method are illustrated by examples. Detection limits vary
      widely, depending on interfering food components, but legal limits below 1 mg/kg
      can hardly be reliably enforced.

PMID- 11469324
TI  - Food aroma partition between packaging materials and fatty food simulants.
AB  - By means of thermal desorption experiments, the partition equilibrium (partition
      coefficient, K) was analysed for six food aroma components (d-limonene, n-decane,
      ethyl caproate, phenylethanol, n-hexanol and hexanal) between three sealable
      pollymer films suitable for direct food contact (ultra-low density polyethylene,
      ULDPE; ionomer, ION; and polyester, PET) and four fatty food simulants (ethanol
      95%, EtOH; sunflower oil, Oil; n-heptane, HEP, and iso-octane, OCT). The results
      showed that aroma scalping is highly dependent on the fatty food simulant
      utilized. Polar aroma components were more sorbed into polymers in the presence
      of a non-polar fatty food simulant, and vice versa. K values in the presence of
      Oil were always between those in EtOH and in HEP or OCT. In general, PET was the
      packaging film which showed the lowest partition coeffecient for non-polar
      components while ULDPE showed the lowest partition for polar aromas. The
      partition equilibrium of mixed d-limonene, ethyl caproate, and n-hexanol was also
      determined. The differences in K values between isolated aromas and mixed aromas
      were small. In general, the most sorbed aroma showed increased partition by
      mixture while the partition of the least sorbed was reduced.

PMID- 11469325
TI  - Zinc levels in foods from southeastern Spain: relationship to daily dietary
      intake.
AB  - The zinc content of 300 food and 79 beverage samples was determined using flame
      atomic absorption spectrometry. Sample recoveries, repeatability, and analyses of
      NIST and CBR-CEC reference materials demonstrated the reliability and accuracy of
      this technique. Mean zinc concentrations varied from 0.02 microg/ml in fresh
      water to 71.0 microg/g (fresh weight) in pork liver. The daily dietary intake of
      zinc for inhabitants of southeastern Spain was estimated to be 10.1 mg (5.5, 4.0,
      0.5, and 0.1 mg Zn/day per person from foods of animal and vegetable origin,
      drinks, and other foods, respectively). Zinc levels found in high protein foods
      (meat, fish, milk products, eggs, dry fruits, cereals and legumes) were
      significantly higher than those found in food with a low protein content
      (vegetables, fruits and drinks) (p < 0.001). A significant linear correlation
      between zinc levels and the corresponding protein content of cereals, legumes and
      dry fruits was found (r = 0.754, p < 0.005). Zinc concentrations in milk samples
      were significantly modified by the thermal treatment (p < 0.001), and the
      skimming (p < 0.05) and calcium enrichment processes (p < 0.001). Shellfish zinc
      levels were also significantly higher than those measured in fish (p < 0.05).
      Mean zinc concentrations found in cheese were statistically higher than those
      determined in the remaining milk products (p < 0.001). Zinc levels measured in
      distilled beverages were also statistically lower than those found in fermented
      ones (p < 0.001).

PMID- 11469326
TI  - Dietary intake of some important mycotoxins by the Swedish population.
AB  - To estimate the intake of some mycotoxins from food in Sweden, approximately 600
      samples were collected and analysed for aflatoxins, ochratoxin A, patulin and
      trichothecenes. Intakes were calculated for average and high consumers among
      adults and children and compared with the tolerable daily intake (TDI) of the
      respective toxin. Mycotoxin levels in the food samples were generally below the
      European/national maximum limits. However, high levels of aflatoxins were found
      in some samples of Brazil nuts and pistachios. The intake of ochratoxin A,
      patulin and trichothecenes was found to be below the temporary, TDI values (tTDI)
      proposed for these toxins by international expert groups, although the intake of
      trichothecenes (expressed as T-2 toxin equivalents) in children with a high
      consumption of cereals was close to the tTDI for T-2 toxin. Since there is to
      date no established numerical tTDI for aflatoxins, such a value was estimated for
      use within the project. The calculated intake of aflatoxins in high consumers
      exceeded this tTDI by a factor of two. In conclusion, the exposure to mycotoxins
      in Sweden did not generally, give rise to any major health concerns in the
      present study. However, the high levels of aflatoxins in certain commodities
      emphasize the need for preventive measures and improved control of toxin levels
      in these food items. Furthermore, the need for regulatory levels for
      trichothecenes in cereal products should be evaluated.

PMID- 11469327
TI  - Trichothecenes, ochratoxin A and zearalenone contamination and fusarium infection
      in Finnish cereal samples in 1998.
AB  - The occurrences and concentrations of trichothecenes, ochratoxin A and
      zearalenone in Finnish cereal samples are presented in this study. Furthermore,
      injections by moulds, especially Fusarium contamination of grains in the same
      samples, are reported. In total 68 cereal samples, including 43 rye, 4 wheat, 15
      barley and 6 oats samples, were collected after a cool and very rainy growing
      season in 1998. A gas chromatograph combined with a mass spectrometric detector
      was used for determination of seven different trichothecenes. A high performance
      liquid chromatograph with a fluorescence detector was used for ochratoxin A and
      zearalenone determination. For the identification of moulds, the grain samples
      were incubated and the moulds were isolated and identified by microscopy. The
      analytical methods were validated for mycotoxin analysis and they were found to
      be adequately reliable and sensitive. Heavy rainfalls in the summer and autumn of
      1998 caused abundant Fusarium mould infection in Finnish cereals, particularly in
      rye. Fusarium avenaceum was the most common Fusarium species found in cereals.
      However, the mycotoxin concentrations were very low and only deoxynivalenol,
      nivalenol and HT-2 toxin were detected. Deoxynivalenol was detected in 54 samples
      in the concentration range 5-111 microg/kg. Nivalenol and HT-2 toxin were
      detected in three and two samples, respectively, in the concentration range 10-20
      microg/kg.

PMID- 11469328
TI  - Evaluation of fumonisin-aflatoxin co-occurrence in Brazilian corn hybrids by
      ELISA.
AB  - The natural co-occurrence of fumonisins and aflatoxins was investigated in
      freshly harvested corn kernels (150 samples, 62 hybrids), acquired from the
      Central-Southern (27 samples, 21 hybrids), Central-Western (86 samples, 51
      hybrids) and Northern (37 samples, 18 hybrids) regions of the State of Parana,
      Brazil using enzyme-linked immunosorbent assay (ELISA). Fumonisins were detected
      in 147 (98%) samples at a concentration range of 0.096 to 22.6 microg/g, while
      aflatoxins were detected in 17 (11.3%). All the aflatoxin-positive samples (range
      38.0-460.0 ng/g) came from the Central-Western region and were co-contaminated
      with fumonisins. Fumonisin contamination was higher in corn from the Northern
      (9.85 microg/g) and Central-Western regions (5.08 microg/g), when compared with
      the Central-Southern region (1.14 microg/g). The overall evaluation detected 62%
      samples with fumonisin levels < or = 5.0 microg/g. Regional differences affected
      fumonisin levels in the same hybrid, regardless of Fusarium count and moisture
      content, suggesting interference from climatic conditions, in addition to the
      local predominance of toxigenic strains of the Fusarium biotype.

PMID- 11469329
TI  - Survey of Romanian slaughtered pigs for the occurrence of mycotoxins ochratoxins
      A and B, and zearalenone.
AB  - Blood serum, kidney, liver and muscle sample per animal were collected from
      slaughtered pigs (n = 52). The samples were analysed for ochratoxin A (OTA) and B
      (OTB) by HPLC methods. Zearalenone (ZEA) in serum was analysed by enzyme
      immunoassay. A total of 98% serum samples were OTA positive in the range of 0.05
      13.4 ng/ml and 85% contained under 5 ng OTA/ml. The incidences of OTA in kidney
      and liver were very similar (79%, 75%) with mean levels of 0.54 ng/g and 0.16
      ng/g, respectively. The lowest incidence (17%) and the lowest mean level
      contamination (0.15 ng/g) were in muscle samples. The mean distribution in
      tissues followed the pattern serum > kidney > liver > muscle (100%; 0.26%; 8.5%;
      2.57%). No kidney, liver or muscle sample was found OTA positive above the
      maximum admitted limit in Romania (5 ng/g). No sample was found to be positive
      for OTB. A very similar OTA contamination (mean = 4.19 ng/ml, coefficient of
      variation = 34.4%) was observed in the serum samples (n = 10) collected from the
      same farm. A possible difference in regional distribution of OTA in Romania is
      suggested. Zearalenone was detected only in 17.3% of the serum samples with a
      maximum concentration of 0.96 ng/ml. This study shows the presence of OTA and ZEA
      in Romanian slaughtered pigs at levels comparable to those reported in other
      countries.

PMID- 11469330
TI  - Analyses of volatile transformation products from additives in gamma-irradiated
      polyethylene packaging.
AB  - Thermal desorption, followed by gas chromatography (GC) with mass spectrometry
      (MS) detection, has been found to allow the rapid identification of volatile
      products resulting from the gamma-irradiation of stabilized, high density
      polyethylene packaging and pure stabilizers. The stabilizers were tris(2,4-di
      tert.butylphenyl) phosphite, octadecyl beta-(2,6-di-tert.butylphenol)-propionate
      and 2,4-di-tert.butylphenol, the latter resulting from phosphite hydrolysis.
      Thermal desorption indicated the formation and release of tert.butylbenzenes,
      such as 1,3-di-tert.butylbenzene upon gamma-irradiation of the HDPE. From a
      comparison of the products from gamma-irradiation of additive-free polyethylene,
      of various pure stabilizers and of related compounds, the tert.butylbenzenes were
      confirmed to result from the irradiation of the phosphite stabilizer and its
      phosphate conversion product. Thermal desorption off-line, in which volatiles
      released by a sample are trapped in sorbents for subsequent desorption in the
      heated GC inlet, is found to be a fast, extremely sensitive method that can be
      used to guide and supplement analyses of compounds extracted by foodstuffs.

PMID- 11469331
TI  - Characterizing the migration of antioxidants from polypropylene into fatty food
      simulants.
AB  - The migration (diffusion and equilibrium) processes of antioxidants (AOs) from
      polypropylene (PP) films of different thicknesses into n-heptane and 95% ethanol
      as fatty food simulants were analysed at 20, 37 and 60 degrees C. Heptane fully
      extracted the AOs from the polymer while a partition equilibrium described the
      migration to ethanol. The kinetics of migration were also studied via the
      diffusion coeffcients. As expected, diffusion was found to be faster when the
      polymer was in contact with heptane, due to polymer swelling by the solvent. The
      kinetics of the process in ethanol was described by different theoretical
      expressions which are discussed. Equations disregarding partition equilibrium
      failed to describe the process and the diffusion coefficient values obtained
      through them were much smaller than the actual ones and dependent on film
      thickness. The results also showed the significance of food simulant selection in
      the analysis of food-packaging interactions and migration variability with
      thickness.

PMID- 11469332
TI  - Three step synthesis of aminocyclohexitols from unprotected aldoses.
AB  - We report an efficient three step synthesis of aminocyclohexitols from
      aldohexoses without the use of protecting groups. Unprotected aldohexoses are
      selectively halogenated at the primary carbon, the aldehyde function is then
      transformed into an oxime ether and finally free radical cyclization of these
      precursors gives aminocyclohexitols.

PMID- 11469333
TI  - Synthesis and evaluation of alpha-fucosidase inhibitory activity of 5a-carba
      alpha-L-fucopyranose and alpha-DL-fucopyranosylamine.
AB  - 5a-Carba-alpha-L-fucopyranose and -alpha-DL-fucopyranosylamine were synthesized
      in conventional manner starting from 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-5a-carba
      beta-D- and -DL-glucopyranosyl bromides, respectively, and assayed for inhibitory
      activity against alpha-fucosidase (bovine kidney). Although the former proved to
      be only a moderate inhibitor (Ki = 4.3 x 10(-5) M), the latter could be shown to
      possess strong inhibitory potential (Ki = 2.3 x 10(-7) M). Diastereoisomeric
      imino-linked 5a'-carbadisaccharides were synthesized by coupling of the racemic
      5a-carba-alpha-fucopyranosylamine and 1,6:3,4-dianhydro-2-azido-2-deoxy-beta-D
      galactopyranose, in order to estimate approximately the inhibitory activity of
      individual optical antipodes of 5a-carba-alpha-fucopyranosylamine.

PMID- 11469334
TI  - Regioselection and orthogonality of the 1-phenyl-3-butenyl (PBU) protecting group
      in glucopyranosides.
AB  - The 1-phenyl-3-butenyl (PBU) protecting group was alternatively introduced in
      position 4 or 6 by regioselective opening of methyl 2,3-di-O-benzyl-4,6-O
      benzylidene-alpha-D-glucopyranose with allyltrimethylsilane in the presence of
      the Lewis acid promoters TMSOTf or AlCl3. The PBU group was selectively removed,
      in presence of t-butyldimethylsilyl, trityl or acetyl protecting groups, with
      acids (TFA) or using Pd(CH3CN)2Cl2.

PMID- 11469335
TI  - Synthesis of a non-natural T-antigen containing glycosphingolipid.
AB  - A non natural glycosphingolipid containing the mucin derived, cancer associated
      disaccharide moiety Galbeta1-->3GalNAc, the T-antigen, alpha linked to a
      ceramide, has been synthesised via the protected disaccharide glycosyl
      trichloroacetimidate. The product has potential as a cancer vaccine.

PMID- 11469336
TI  - Sugar-lectin interactions: sugar clusters, lectin multivalency and avidity.

PMID- 11469337
TI  - Synthesis and antiproliferative activity of O-silylated nucleoside triazene N
      oxide derivatives.
AB  - A series of modified nucleosides bearing at varied positions of the sugar moiety
      one 3-aryl-1-triazeno N1-oxide group and a variable number of O-TBDMS groups have
      been prepared and their cytotoxicities and cytostaticities measured on different
      cell lines. Nucleosides bearing an aryltriazeno N-oxide group and O-TBDMS groups
      are either devoid of cytotoxicity or possess a selective cytotoxicity. On the
      other hand, nucleosides bearing one triazeno group and no silyl group are devoid
      of cytotoxicity and silylated nucleosides without triazeno group are generally
      either devoid of cytotoxicity or unselectively cytotoxic. This indicates that the
      O-TBDMS group per se is not cytotoxic.

PMID- 11469338
TI  - Density dependent interaction of polymeric analogs of beta-galactosyl ceramide
      with GP120 of human immunodeficiency virus 1.
AB  - Polymerizable analog of beta-galactosyl ceramide (beta-GalCer) was synthesized
      and converted to water-soluble polymers of beta-GalCer (poly-beta-GalCer) having
      specific affinity with recombinant gp120 of human immunodeficiency virus (HIV)-1
      or V3 loop derived synthetic peptide. It was demonstrated that the binding
      affinity of poly-beta-GalCer greatly depends on the density of GalCer moieties on
      the polymer backbone.

PMID- 11469339
TI  - Beta-cyclodextrin-linked chitosan beads: preparation and application to removal
      of bisphenol A from water.
AB  - Water-insoluble and highly porous chitosan beads having an ability to form
      inclusion complexes have been synthesized by treatment of a solution of chitosan
      in aqueous acetic acid with aqueous NaOH followed by crosslinking and reductive
      alkylation with 2-O-formylmethyl-beta-cyclodextrin. Preliminary experiments for
      its application to removal of endocrine disrupting chemicals were carried out
      using a column of the resulting beads and bisphenol A as the model substrate.

PMID- 11469340
TI  - Surgical pathology versus molecular biology.

PMID- 11469341
TI  - Histologic recurrence-free outcome after orthotopic liver transplantation for
      chronic hepatitis B.
AB  - Recurrent hepatitis B (HB) following orthotopic liver transplantation (OLT) for
      chronic disease is common. However, an unpredictable minority of patients follow
      a recurrence-free course. Clinical, virologic, and pathologic data from patients
      surviving longer than 60 days (n=24) with pathologically confirmed nonrecurrence
      of HB following OLT for chronic HB were reviewed to identify factors associated
      with nonrecurrence of HB. Nine of 24 patients had no histologic and
      immunohistologic evidence of recurrent HB. In addition to pre-OLT hepatitis B e
      antigen (HBeAg) negativity, coexisting delta and anti-HB therapy/prophylaxis,
      other acquired viral infections and their therapy, and severe acute rejection due
      to noncompliance were considered the possible protective factors against HB
      recurrence in these 9 patients. Histologic and, particularly immunopathologic,
      evaluation of liver biopsies must be utilized in definitively diagnosing
      recurrence of HB.

PMID- 11469342
TI  - Histologic types of thymoma associated with pure red cell aplasia: a study of
      five cases including a composite tumor of organoid thymoma associated with an
      unusual lipofibroadenoma.
AB  - The histologic type of thymomas associated with pure red cell aplasia (PRCA) has
      generally been regarded to be predominantly the spindle cell type. The 5 thymomas
      associated with PRCA we studied showed various histologic types and none of them
      was a spindle cell thymoma. Some cases reported as spindle cell thymoma
      associated with PRCA in the literature might not be spindle cell type. The
      discrepancy could be due to the lack of consensus in the histologic
      classification of thymomas in the past. Our study showed that thymomas associated
      with PRCA lacked a strong correlation with a particular histologic type and the
      pathogenesis of PRCA associated with thymoma did not seem to be related to the
      histologic type. One of our cases was an unusual composite tumor of an organoid
      thymoma (WHO type B1) and a hitherto undescribed "lipofibroadenoma." The clinical
      outcome was influenced by the invasive character and the histologic type of the
      thymoma.

PMID- 11469343
TI  - Cytokeratin subunits of inclusion bodies in rhabdoid cells: immunohistochemical
      and clinicopathological study of malignant rhabdoid tumor and epithelioid
      sarcoma.
AB  - Extrarenal malignant rhabdoid tumor (MRT), which is recognized as being
      histologically similar to renal MRT, is characterized by the presence of
      "rhabdoid cell" (RC) and a highly aggressive biological behavior. Recently it has
      been proposed that "proximal variant" of epithelioid sarcoma (ES), whose
      morphology is similar to that of MRT, actually has a more aggressive clinical
      course than classical type ES. Detailed immunohistochemical analysis of
      cytokeratin (CK) subunits was performed in 3 cases of extrarenal MRT, 3 cases of
      renal MRT, and 11 cases of ES comprising 2 "proximal variants" and 9 classical
      types. Renal and extrarenal MRTs showed positive immunoreactivity for both CK8
      and CK18. Classical type ESs were diffusely positive, not only for CK8 and CK18,
      but also for other cytokeratin subunits including CK4, 6, 10, 13, 16, 17, and
      "high-molecular-weight" CKs (CK1, 5, 10, and 14). On the other hand, proximal ES
      revealed limited immunohistochemical reactivity for cytokeratins, compared with
      classical ES. In conclusion, the inclusion bodies of RCs show immunoreactivity
      confined to CK8, CK18, and vimentin. Furthermore, ES has additional CK
      expressions, while proximal ES possesses characteristics intermediate between
      those of classical ES and those of external MRT.

PMID- 11469344
TI  - Renal cell carcinoma metastatic to the testis and its adnexa: a report of five
      cases including three that accounted for the initial clinical presentation.
AB  - Five cases of renal cell carcinoma metastatic to the testis or its adnexa are
      described, including 3 that represented the initial presentation and mimicked
      primary testicular neoplasms. The patients ranged from 46 to 85 years of age.
      Three presented with self-identified testicular masses. One patient was
      investigated because of fever of unknown origin and was found to have a left rib
      metastasis. Further work-up led to the discovery of a testicular mass. The final
      patient had a tumor of the spermatic cord that was examined without knowledge
      that he had a prior renal neoplasm. All the tumors were unilateral. They ranged
      from 1.8 to 5.0 cm; multiple tumor nodules were present in one of them but the
      others were discrete solitary masses. Four tumors were yellow/yellow-tan, and one
      was gray. On microscopic examination all the tumors were of the clear cell type.
      Patterns included solid sheets, acini, cysts, alveoli, and trabeculae. Two had
      prominent vascular invasion. Diagnoses initially entertained in these cases
      included Sertoli cell tumor, Sertoli-Leydig cell tumor, and clear cell
      cystadenoma of the epididymis. In 3 cases a kidney tumor was discovered 2 to 4
      weeks after the diagnosis of renal cell carcinoma metastatic to the testis was
      rendered. On follow-up two patients died of tumor, and two were alive (5 months
      and 1 year) after orchiectomy. The diagnosis of renal cell carcinoma metastatic
      to the testis should be considered in evaluating a clear cell tumor of the
      testis, particularly in an older male or if the appearance suggests a Sertoli
      cell tumor. The differences in survival between metastatic renal cell carcinoma
      and sex cord-stromal tumors indicate the importance of considering the former in
      the differential.

PMID- 11469345
TI  - Obtaining high-quality photomicrographs at scanning magnification.

PMID- 11469346
TI  - A look at an unusual animal kingdom. Part II. Sea and earth's creatures.

PMID- 11469347
TI  - Glomangiomyoma of the left middle finger.

PMID- 11469348
TI  - Multinucleated lipoblast.

PMID- 11469349
TI  - Diagnostic errors in surgical pathology uncovered by a review of malpractice
      claims. Part IV. Melanoma.

PMID- 11469350
TI  - Papillary thyroid carcinoma of the thyroglossal duct cyst: comparative
      cytohistologic and immunochemical study of 2 new cases and review of the
      literature.
AB  - We report a cytohistologic and immunohistochemical study of 2 cases of papillary
      thyroid carcinoma occurring in a thyroglossal duct cyst. The patients were a 21
      year-old woman and a 48-year-old man. Needle aspiration cytology smears were
      consistent with papillary thyroid carcinoma. The Sistrunk procedure was done.
      Papillary carcinoma was found within a thyroglossal duct cyst. In 1 case, the
      tumor spread outside the cyst. Follow-up was uneventful in both patients (2 and 9
      years, respectively). Our results would indicate that papillary carcinoma of
      thyroglossal duct cyst, though indistinguishable from its thyroid homologue, has
      a more indolent course and could therefore be singled out as a clinicopathologic
      entity. Needle aspiration cytology reliably assists in planning patient
      management.

PMID- 11469351
TI  - Ewing tumor: tumor biology and clinical applications.
AB  - The Ewing tumor family includes classical Ewing's sarcoma of bone and soft
      tissues, peripheral primitive neuroectodermal tumors (pPNET), Askin tumor, and
      other less frequent variants. This group of tumors is defined by the consistent
      presence of chromosomal translocations resulting in gene fusions between EWS gene
      and a member of the ETS family of transcription factors, mainly FLI1 and ERG.
      Analogous fusions are seen in other solid developmental tumors, like desmoplastic
      small round cell tumor. These fusions, which are consistently present and tumor
      specific, control transcription of several target genes, largely unknown but
      critical to cell proliferation and differentiation. Therefore, gene fusions are
      useful to diagnose and classify small round cell tumors, have prognostic
      significance, are probably useful to detect micrometastasis and monitor minimal
      residual disease, and are potential therapeutic targets. Secondary molecular
      alterations, which include mutations of cell cycle regulatory genes, are not
      tumor-specific but are related to progression and may have prognostic value. The
      Ewing tumor family represents a paradigm of the application of the knowledge of
      biology of neoplasia to the clinical management of patients.

PMID- 11469352
TI  - Erdheim-Chester disease with extensive marrow necrosis: a case report and
      literature review.
AB  - Erdheim-Chester disease is a rare systemic disorder characterized by a fibrosing
      xanthogranulomatous infiltration of multiple organs. We report a case of Erdheim
      Chester disease with diffuse necrosis leading to difficulty in making a prompt
      diagnosis. Radiologically, osteosclerotic lesions with osteolytic element
      involved metadiaphyses of both proximal tibia, and retroperitoneal infiltrations
      encasing both kidneys, both adrenals, and aorta were found. A biopsy of the tibia
      showed diffuse infiltration of foamy histiocytes, Touton-type giant cells, and
      fibroblastic cells associated with extensive coagulative necrosis.
      Immunohistochemically, foamy histiocytes were positive for CD68 and peanut
      agglutinin and negative for S-100 protein. A few Langerhans' cells, which were
      difficult to identify in hematoxylin-eosin stain, were highlighted by immunostain
      for S-100 protein. The patient received supportive therapy and was alive 1 1/2
      years after diagnosis, with newly developed bilateral retrobulbar lesions and
      worsened heart failure.

PMID- 11469353
TI  - Phyllodes tumor in ectopic breast tissue of the vulva.
AB  - Phyllodes tumor arising from ectopic breast tissue of the vulva is an extremely
      rare occurrence. A case is reported in a 34-year-old nulligravida woman,
      presenting as a nodule on the left labium majus. A simple excision was carried
      out, and no recurrence has been detected after 18 months of follow-up.

PMID- 11469354
TI  - Classification of thyroid tumors: is a change necessary?

PMID- 11469355
TI  - Public meetings deserve proper science.

PMID- 11469356
TI  - Who contracts for primary care?
AB  - The implications of the 1997 NHS (Primary Care) Act have been largely overlooked
      in the rush to establish Primary Care Groups. Allowing health authorities to
      develop local contracts for primary care has far-reaching implications and is an
      important departure from the national system of negotiation that has
      characterized general practice to date. This paper describes a content analysis
      of a sample of Personal Medical Services (PMS) pilot contracts. In the first year
      little attention has been given to achieving cost savings or greater efficiency
      and few contracts promote clinical guidelines. The difficulties of specifying
      services sensitive to local health needs are highlighted and the national
      Statement of Fees and Allowances (the 'Red Book') may not be swiftly supplanted.
      However, the pilots have introduced innovations such as salaried general
      practitioners, nurse-led services and NHS trust-managed care. The development of
      local contracts provides a valuable learning experience for general practitioners
      and health authorities in advance of the establishment of Primary Care Trusts.

PMID- 11469357
TI  - Comparison of UK and US methods for weighting and scoring the SF-36 summary
      measures.
AB  - BACKGROUND: The SF-36 is a widely used measure of health status that can be
      scored to provide either a profile of eight scores or two summary measures of
      health, the Physical Component Summary and Mental Component Summary (PCS and
      MCS). Scoring of the summary scales is undertaken by weighting and summing the
      original eight dimensions. These weights are gained from factor analysis of data
      from a general population and have been assumed to be country specific. However,
      it has been suggested that the weights gained from the US developers could be
      applied to all datasets, throughout the world, for purposes of comparability and
      simplicity. The purpose of this study is to evaluate US and UK scoring schemes in
      a UK population dataset, and in a cohort study of elderly congestive heart
      failure patients receiving standard therapy and a trial of open vs laparoscopic
      surgery for hernia repair. METHODS: This paper compares algorithms developed in
      the USA and the UK for the calculation of the Physical and Mental Health Summary
      scores (PCS and MCS) for the SF-36 health status measure. In this study the PCS
      and MCS were calculated using a weighting scheme recommended by the developers
      and derived from a US population sample dataset, as well as being calculated from
      weights derived from an UK population sample dataset. RESULTS: The two methods
      produced similar results, both cross-sectionally and in the assessment of change.
      CONCLUSIONS: It is suggested that it may be necessary to weight the PCS and MCS
      using only the original US algorithms, which will lead to more uniform analysis
      of datasets and may also lead to greater uptake of the summary measures.
      Furthermore, the results would suggest that in international trials the SF-36 can
      be adopted and summary scores calculated for countries where no large-scale
      normative dataset is available. However, further research is needed to determine
      that the similarity of results gained using UK and US algorithms is not an
      idiosyncratic feature of the UK data. Studies to verify the findings reported
      here are required from other countries.

PMID- 11469358
TI  - Tanning and sunburn: knowledge, attitudes and behaviour of people in Great
      Britain.
AB  - BACKGROUND: A representative sample of the British population was interviewed to
      identify the factors associated with sunburn and intention to tan, and the source
      from which people obtained their information about the risks of sun exposure.
      METHODS: As part of its rolling Omnibus survey, the Office for National
      Statistics interviewed a randomly selected representative sample of 1858 adults
      (aged 16 or over) in Great Britain in October 1996. The analysis and
      interpretation of the resulting data form the basis of this study. RESULTS: The
      response rate was just below 70 per cent. Forty-three per cent of men and 35 per
      cent of women reported sunburning in the 12 months to October 1996. Factors
      associated with sunburn were: being male, having a skin that tans with difficulty
      and being younger. Concerning 'intention to tan', 34 per cent of men and 39 per
      cent of women admitted trying. There were associations with having a skin that
      tans easily, and, less strongly, with being younger. There was a clear
      association between trying to tan and severity of sunburn. Most people identified
      television as their main source of information about the dangers of sun exposure,
      and the majority had seen the sunburn forecasts on weather reports. Comparison
      with a previous Omnibus sunburn survey from 1993 shows little change in the
      proportion of the population becoming sunburnt, but some increase in the
      proportion of men intending to tan. CONCLUSIONS: The data allow an insight into
      current sun-related behaviour and whether there has been a change since 1993.
      Health promotion campaigns warning about the risk from the sun may have increased
      awareness, but have thus far failed to reduce the proportion becoming sunburnt.
      It is time to re-evaluate the thinking behind such programmes.

PMID- 11469359
TI  - Costs and disability among stroke patients.
AB  - BACKGROUND: The high costs of health and social care support for stroke
      survivors, and the development of new service arrangements, have concentrated
      growing attention on economic issues. However, there are few data on costs and
      their association with levels of disability. METHODS: Secondary analyses of data
      from the OPCS (Office of Population Censuses and Surveys) Surveys of Disability
      conducted in the mid-1980s were used to examine service utilization and costs for
      more than 1000 people who have had a stroke. Costs were estimated for all health
      and social care services. Regression analyses examined the cost-disability
      association in the context of other covariates for people living in private
      households. RESULTS: Disability problems were common among stroke survivors,
      particularly in relation to locomotion, self-care and holding. Among people
      living alone, the major contributors to costs were in-patient care (Pound
      Sterling 27 per week) and home help (Pound Sterling 30 per week). Among people
      living with others, in-patient hospital care was also a major cost (Pound
      Sterling 28 per week). Other services costing more than Pound Sterling 5 per week
      were general practitioner consultations, hospital out-patient care and day centre
      attendances. Resource use patterns varied considerably. Costs were associated
      with severity of disability, time since stroke and whether the person was living
      alone. Looking at the overall balance of care, a greater proportion of stroke
      survivors with severe disability were resident in communal establishments.
      CONCLUSION: The analyses provide a baseline from which more recent local studies
      and evaluations can be compared. Key issues for economic studies of stroke are
      the inclusion of a broad range of services, a reasonable duration of follow-up
      and consideration of the impact of the substitution of informal for formal
      services.

PMID- 11469360
TI  - Prescribing of beta-2 agonists and inhaled steroids in England: trends between
      1992 and 1998, and association with material deprivation, chronic illness and
      asthma mortality rates.
AB  - BACKGROUND: British Thoracic Society guidelines published in 1990, revised in
      1993 and 1997, recommended that general practitioners should make greater use of
      inhaled steroids in the management of asthma. British Thoracic Society guidelines
      have also been published on the management of chronic obstructive pulmonary
      disease. The objective of this study was to examine trends in the prescribing of
      beta-2 agonists and inhaled steroids in England between 1992 and 1998, and to
      investigate the variation at health authority level in the use of these drugs.
      METHODS: This was an observational study using prescribing analysis and cost
      (PACT) data, mortality data and data from the 1991 Census for all 100 health
      authorities in England. RESULTS: The number of defined daily doses of beta-2
      agonists prescribed per quarter increased by 20 per cent, from 142 million to 170
      million between June 1992 and March 1998. The number of defined daily doses of
      inhaled steroids prescribed per quarter increased by 78 per cent during the same
      period, from 69.9 million to 124.7 million. The ratio of inhaled steroids to beta
      2 agonists increased from 0.49 to 0.73. The number of items per 1000 specific
      therapeutic group age-sex related prescribing units (STAR-PUs) in 1997 in health
      authorities in England varied from 41 to 115 for beta-2 agonists and from 24 to
      68 for inhaled steroids. The ratio of the number of items of inhaled steroids to
      beta-2 agonists varied from 0.50 to 0.70. At health authority level, prescribing
      rates were most strongly associated with the percentage of patients reporting
      chronic illness (correlation coefficient 0.82 for beta-2 agonists and 0.72 for
      inhaled steroids). There were significant negative correlations between the ratio
      of inhaled steroids to beta-2 agonists and both Jarman deprivation scores (r = 
      0.51) and chronic illness (r = -0.38). There were no significant associations
      between health authority prescribing rates and death rates from asthma in people
      aged 5-44 years. CONCLUSIONS: Prescribing of inhaled steroids has risen more
      quickly than that of beta-2 agonists between 1992 and 1998, resulting in a marked
      increase in the ratio of inhaled steroids to beta-2 agonists. At health authority
      level, there remains a wide variation in the use of beta-2 agonists and inhaled
      steroids.

PMID- 11469361
TI  - An assessment of the Nam Pehchan computer program for the identification of names
      of south Asian ethnic origin.
AB  - BACKGROUND: An assessment was made of the usefulness and accuracy of a computer
      program for the identification of the south Asian population through the
      classification of names on a disease register. METHODS: The computer program, Nam
      Pehchan, was used to classify names as either south Asian or non south Asian. The
      results were compared with a reference standard, which combined use of the
      program with visual inspection. The latter was facilitated by a computer
      generated dictionary of common non south Asian names. The data set consisted of
      356,555 cases of incident cancer (ICD9: 140-208) registered between 1990 and 1992
      by Thames, Trent, West Midlands and Yorkshire cancer registries. RESULTS: Nam
      Pehchan classified 5506 cases as south Asian. Visual inspection identified 2024
      false positives (36.8 per cent of all cases identified as south Asian by Nam
      Pehchan) and 363 false negatives (9.5 per cent of those identified by the
      reference standard). Compared with the reference standard, Nam Pehchan had a
      sensitivity of 90.5 per cent and a positive predictive value of 63.2 per cent.
      CONCLUSION: The Nam Pehchan program quickly identified a high proportion of the
      names classified as south Asian by the reference standard, but the high false
      positive rate means that the program alone is not an adequate single strategy.
      The time-consuming process of inspection of program negatives for large data sets
      can be substantially reduced by comparison with dictionaries of common non south
      Asian names.

PMID- 11469362
TI  - Mortality attributable to drinking, drinking too much, or drinking too little: a
      comparison of methods.
AB  - BACKGROUND: The existence of a U-shaped relationship between alcohol consumption
      and all-cause mortality complicates the calculation and interpretation of
      mortality attributable to alcohol consumption. METHODS: We used the relationships
      between all-cause mortality and alcohol consumption from four British cohort
      studies. For each study we defined a 'sensible drinking level' asthe level with
      lowest observed mortality. We estimated the fractions of deaths that were
      attributable to (1) any drinking (compared with not drinking), (2) drinking more
      than the 'sensible level', and (3) drinking less than the 'sensible level'.
      RESULTS: Data from the Doctors' study suggest that on balance 22.3 per cent of
      deaths are prevented by alcohol consumption, yet the fractions of deaths
      attributable to drinking more than 8-14 units per week and less than 8-14 units
      per week are nearly equal (6.5 per cent and 6.4 per cent, respectively). In a
      sensitivity analysis we show that it is possible for alcohol consumption to
      prevent deaths overall yet for more deaths to be attributable to drinking above a
      sensible level than are attributable to drinking below the sensible level.
      CONCLUSIONS: The balance of deaths attributable to or prevented by alcohol
      consumption provides no information about the deaths attributable to drinking
      above or below sensible levels. Using all-cause data in this way is likely to
      exaggerate the protective effect of alcohol consumption, so our results are only
      illustrative.

PMID- 11469363
TI  - Evaluation of a scheme for the pre-distribution of stable iodine (potassium
      iodate) to the civilian population residing within the immediate countermeasures
      zone of a nuclear submarine construction facility.
AB  - BACKGROUND: The Barrow-in-Furness stable iodine (potassium iodate) tablet pre
      distribution scheme was the first of its kind to be introduced to protect the
      population living around a fixed site nuclear facility in the United Kingdom. Pre
      distribution schemes have attracted critical comment principally because the
      certainty of availability of potassium iodate tablets was unknown. This study
      aimed to establish the reliability of such a scheme. METHOD: A structured
      interviewer-administered survey of a random sample of households served by the
      pre-distribution scheme was carried out using a standardized questionnaire.
      RESULTS: The ability of this scheme to provide stable iodine protection declined
      from 100 per cent to 60 per cent coverage over a period of two years for the
      designed worst-case demand (the ability to supply stable iodine tablets to all
      household residents normally living within the pre-distribution scheme zone).
      CONCLUSIONS: Pre-distribution has value in areas where evacuation to a centre
      where stable iodine tablets are available or post-accident distribution to
      sheltering households is difficult. The value of such a scheme must be calculated
      against a predictable decline in its effectiveness. In implementing such a scheme
      it should be noted that this decline in coverage can be reduced by calculating
      the frequency with which tablet packs are redistributed to take account of this
      factor.

PMID- 11469364
TI  - Private or NHS General Dental Service care in the United Kingdom? A study of
      public perceptions and experiences.
AB  - BACKGROUND: Recent changes in the NHS General Dental Service have led to a
      reduction in the availability of NHS dental care and increased charges. This
      study explores public and user views and experiences of NHS and private dental
      care in the light of these changes. METHODS: The study employed a combination of
      quantitative and qualitative methods. The first phase involved a postal survey of
      a random sample of adults on the electoral registers in a county in Southern
      England, which yielded a response rate of 55 per cent (n = 1506). Follow-up face
      to-face interviews were carried out with sub-samples (n = 50) selected from
      survey respondents. RESULTS: The evidence shows greater satisfaction with certain
      aspects of private care than with NHS dental care and suggests that the decline
      in perceived quality of NHS care is less to do with the quality of dental
      technical skills and more to do with perceived access and availability. However,
      there was general support for the egalitarian principles associated with NHS
      dentistry, although payment for dental care by users was acceptable even though
      dentistry on the NHS was preferred. CONCLUSION: The shift in the balance of NHS
      and private dental care reflects the interests and preferences of dentists rather
      than of the public. It suggests, however, that a continued shift towards private
      practice is a trend that the public will not find acceptable, which might limit
      the extent of expansion of private practice.

PMID- 11469365
TI  - Rating the appropriateness of coronary angiography, coronary angioplasty and
      coronary artery bypass grafting: the ACRE study. Appropriateness of Coronary
      Revascularisation study.
AB  - BACKGROUND: Previous studies investigating the appropriateness of invasive
      management of coronary disease had not reported the internal consistency of their
      ratings and may now be out of date. The aim of this study was to measure the
      influence of clinical factors on contemporary ratings of the appropriateness of
      coronary angiography, percutaneous transluminal coronary angioplasty (PTCA) and
      coronary artery bypass graft (CABG) in the Appropriateness of Coronary
      Revascularisation (ACRE) study. METHODS: The Delphi-RAND technique was used, in
      which an expert panel (four cardiologists, three cardiothoracic surgeons, a
      general physician and a general practitioner), meeting in 1995, rated mutually
      exclusive indications (n = 2178 for angiography, n = 995 for PTCA and n = 984 for
      CABG). The main outcome measures were the appropriateness category
      (inappropriate, uncertain or appropriate) for each of the three procedures and
      treatment preference. RESULTS: For revascularization, the strongest determinant
      of inappropriateness was coronary anatomy. The odds ratio (OR) for inappropriate
      PTCA was 10.6 (95 per cent confidence interval (CI) 4.8-23.5) for the effect of
      left main stem or three-vessel disease versus single-vessel disease, and for CABG
      it was 0.06 (95 per cent CI 0.03-0.15). The number of diseased vessels was
      strongly related to preference for medical, PTCA or CABG treatment (p for linear
      trend <0.001). Mild versus severe anginal symptoms were associated with
      inappropriate angiography (OR 2.0 (95 per cent CI 0.9-9.8), although this effect
      was stronger when only the cardiologists' ratings were considered (OR 10.1 (95
      per cent CI 2.4-42.6)). CONCLUSION: These are the first UK ratings of
      appropriateness covering all three procedures. The associations with clinical
      factors provide evidence of the internal consistency of these ratings.
      Prospective validation of these ratings against clinical outcomes is under way in
      the ACRE study.

PMID- 11469366
TI  - Clinical governance for public health professionals.
AB  - This paper examines the issues specific to clinical governance for public health
      professionals. It highlights three levels at which public health is capable of
      promoting clinical governance: within the specialty of public health, across
      other National Health Service (NHS) organizations and as part of the public
      health responsibilities of health authorities. Current work is reviewed, and its
      focus on hospital and community NHS Trusts is noted. Current thinking on the
      introduction of clinical governance into clinical practice is interpreted to
      provide a framework for its development in public health professional practice.

PMID- 11469367
TI  - A study of leukaemia in Glasgow in connection with chromium-contaminated land.
AB  - BACKGROUND: In 1991, soil pollution was found around the site of a former
      chromium-processing factory in Glasgow, Scotland. Levels of chromium in soil were
      above limits considered as safe, although a risk assessment concluded that
      population exposure was likely to be below occupational levels. As an excess
      incidence of leukaemia has been suspected in the area, it was decided to
      investigate a possible relationship between the pollutant and the illness.
      METHODS: The ensuing study was descriptive-geographical. In the absence of better
      data, levels of exposure were assumed to decrease with distance from the centre
      of the polluted area. Leukaemia and population figures were obtained for each of
      nine concentric rings by aggregation of data available at the Enumeration
      District level. The null study hypothesis was that relative risk (as measured by
      Poisson regression) would not follow a definite trend with distance from the
      centre. Sex, age and levels of deprivation were taken into account. RESULTS:
      Relative risks by variables other than distance followed previously known
      patterns for leukaemia. No evident pattern by distance was found. After
      regroupings inside the variables, a significant excess of leukaemia was found for
      intermediate distances from the pollutant. CONCLUSIONS: No evidence was found of
      a possible relationship between soil pollution by chromium and leukaemia in the
      general population. Nonetheless, the excess noticed by the study warrants further
      research.

PMID- 11469368
TI  - Guidance for control of parvovirus B19 infection in healthcare settings and the
      community.
AB  - Interventions for parvovirus B19 infection need to balance the low risk of
      infection at a population level with the potential for serious adverse outcome
      for particular groups, notably the fetus, people with haemoglobinopathies and the
      immunocompromised. This guidance aims to assist the local decision-making process
      to be as evidence-based as the available evidence allows.

PMID- 11469369
TI  - Public health physicians who contribute to on-call communicable disease control
      duties: national comparative clinical audit by questionnaire survey.
AB  - BACKGROUND: In most health authorities in the UK, general public health
      physicians provide out-of-hours cover for specialists in communicable disease
      control. Although communicable disease control was part of their specialist
      training, there is no current formal mechanism to enable these doctors to keep up
      to date. The Faculty of Public Health Medicine has an active Continuing
      Professional Development Programme. A new initiative aimed to assess the
      knowledge of general public health physicians who take part in on-call
      communicable disease control rotas, or may do so in the future, by means of an
      educational clinical audit exercise. METHODS: Experts in communicable disease
      control developed a questionnaire containing a selection of scenarios, covering
      six different situations that might arise on-call. This was circulated to all
      members of the Faculty, but participation was voluntary. Answers were marked
      against model answers agreed by the experts. Results were analysed by positions
      held by participants. RESULTS: Response was unacceptably low. Overall scores
      ranged from 15 per cent to 89 per cent with a mean of 63 per cent. There was a
      trend of improvement in marks from those not normally involved in on-call (mean
      score 56.1 per cent (95 per cent confidence interval 51.6-60.7 per cent)) through
      Directors of Public Health (58.4 (54.9-62.0) per cent), Consultants (62.8 (60
      65.6) per cent), and specialist registrars (67.9 (65.2-70.6) per cent), to
      Consultants in Communicable Disease Control (70.9 (68.1-73.6) per cent).
      CONCLUSION: The public health physicians who took part in this audit appear to be
      competent in their knowledge of communicable disease control, and particularly
      good at dealing with meningitis and salmonella, which are frequently encountered
      out of hours.

PMID- 11469370
TI  - 'Failure to rescue' as a measure of quality of hospital care: the limitations of
      secondary diagnosis coding in English hospital data.
AB  - Although it is widely recognized that quality of care varies between hospitals, a
      robust and valid measure of outcome that can be used in comparisons has proven
      elusive. One measure that has recently been proposed by US researchers is the
      'failure to rescue' (FTR) rate. This is based on the assumption that, whereas
      complications may reflect both patient severity and health care factors, the
      ability to save patients once complications arise is much more closely related to
      the quality of health care. We describe an evaluation of FTR in a national sample
      of English hospitals using hospital episode data. We found that the rate of
      secondary diagnosis recording in England is about one-tenth that in the United
      States. The FTR rate would be highly sensitive to variations in the completeness
      of coding of secondary diagnoses. Unless coding is of uniformly high quality, any
      attempt to compare severity adjusted outcomes will be potentially unreliable.

PMID- 11469371
TI  - Trends in acute admissions: a study of one English district general hospital.
AB  - BACKGROUND: The aim of the study was to determine whether significant daily and
      hourly variations in acute admissions to hospital were evident over time, and to
      determine whether significant changes in patient and management characteristics
      had occurred over time. METHODS: Time-trend and cross-section analysis of
      admissions was carried out, for samples between 1986 and 1995, using manual
      records from the transit ward, Doncaster Royal Infirmary. RESULTS: Mean daily
      admissions at weekends were significantly lower than those occurring during the
      working week. During the day, the admission rate peaked at around noon and
      gradually declined thereafter. Patients arriving during the night tended to be
      younger and were more likely to be male. Age was a significant predictor of
      subsequent patient management following arrival. Overall, the number and mean age
      of arriving patients had increased by the end of the investigation period,
      although the proportion of patients being sent home from the transit ward did not
      vary over time.

PMID- 11469372
TI  - Royal College of Physicians of Edinburgh, Consensus Conference on Lipid Lowering
      to Prevent Vascular Events, 17 and 18 March 1999--consensus panel.

PMID- 11469373
TI  - Quarterly Communicable Disease Review. April to June 1999--from the PHLS
      Communicable Disease Surveillance Centre.

PMID- 11469374
TI  - Academic training in public health medicine in the UK: findings from an
      electronic mail census.

PMID- 11469375
TI  - Comparative cost effectiveness supports the use of meningococcal vaccine in
      schools after a single case.

PMID- 11469376
TI  - Should we be doing more to prevent Group C meningococcal infection in school age
      children? How can we decide?

PMID- 11469377
TI  - Know your limitations: not just for clinicians. Estimation of confidence
      intervals is not straightforward.

PMID- 11469378
TI  - General Household Survey.

PMID- 11469379
TI  - Out-of-hours care in the UK--generalizability of research findings.

PMID- 11469380
TI  - Health-promoting schools: new challenges to school teachers.

PMID- 11469381
TI  - Biologic agents in the treatment of rheumatoid arthritis.
AB  - Advances in the understanding of the pathogenesis of rheumatoid arthritis (RA) as
      well as improved biotechnology has enabled selective targeting of the pathogenic
      elements of disease. Targeting cell recruitment through adhesion molecules has
      been shown to be successful in pre-clinical murine models. Results of studies of
      an anti-ICAM-1 monoclonal antibody and anti-sense oligonucleotides have been
      encouraging. An alternate approach to inhibiting recruitment has been the
      targeting of chemoattractant molecules ie. chemokines. Important advances have
      been made in cytokine directed therapy targeting TNFalpha and IL-1. TNF
      antagonists (anti-TNF monoclonal antibody/soluble TNF receptor Fc fusion protein)
      have resulted in rapid and substantial improvement in signs and symptoms of
      disease as well as disease modification, shown by slowing of radiological
      progression. IL-1 receptor antagonist protein appears to have a significant
      effect on radiological progression despite a modest effect on symptoms and signs.
      Studies using anti-inflammatory cytokines such as IL-10 are in progress. A more
      recent therapeutic approach has been to target T-cell activation by interfering
      with co-stimulatory complexes such as CD40L/CD40 and CD28/CD80 and CD86. Both pre
      clinical and preliminary clinical studies in human subjects support the concept.
      Another approach involving T-cell receptor peptide vaccination with VB peptides
      over-utilized in RA synovium has shown to be beneficial. Targeting the cytokines
      driving T-cells in the RA synovium ie. IL-12 & IL-15 has also proven beneficial
      in animal studies. Recent attention has also been directed toward the invading
      synovial fibroblast using Fas-FasL mediated apoptosis. Pre-clinical studies in
      which angiogenesis and osteoclast activation are targeted have been encouraging.
      In conclusion, the proof of principle has been established that selective
      targeting of pathogenic elements of disease results in substantial improvement in
      signs and symptoms as well as disease progression. Improved efficacy is expected
      with more aggressive targeting of the pathogenic elements.

PMID- 11469382
TI  - Cytokines in candidiasis and aspergillosis.
AB  - Both innate and T helper (Th) immunity play a central role in fungal infections.
      A bi-directional influence exists between the two compartments of the immune
      system, mainly occurring through cytokine production. On the one hand, protective
      Th1 or nonprotective Th2 cells mediate resistance or susceptibility to
      disseminated and localized fungal infections by secreting cytokines with
      activating or deactivating signals for effector phagocytic cells. On the other
      hand, cells of the innate immune system regulate the development of antifungal T
      helper responses by producing directive cytokines, such as interleukin (IL)-12
      and IL-10. In experimental models of Candida albicans and Aspergillus fumigatus
      infections, the administration or neutralization of selective cytokines and the
      use of cytokine-deficient mice have revealed the existence of a hierarchical
      pattern of cytokine mediated regulation of antifungal Th cell development and
      effector function. A finely regulated balance of directive cytokines, rather than
      the relative absence of opposing cytokines, appears to be required for optimal
      development and maintenance of protective Th1 reactivity to fungi. Thus, it is
      conceivable that some cytokines may have beneficial or deleterious effects on
      infection, depending on the dose and timing of endogenous production or exogenous
      administration. A better understanding of the different, sometimes unexpected,
      roles of cytokines is required for their use in prophylaxis and therapy of fungal
      infections, either alone or in combination with antifungal agents.

PMID- 11469383
TI  - Immunoglobulin VH domains and beyond: design and selection of single-domain
      binding and targeting reagents.
AB  - Identification of the smallest antibody fragment still capable of binding to
      antigen has progressed from full antibody molecules to Fab and recombinant single
      chain Fv fragments. Now, a further reduction to single domain binding proteins
      based upon immunoglobulin VH and VH-like domains offers exciting prospects in the
      development of novel immunotherapeutics and immunodiagnostics. Minimisation of
      the antigen-binding fragment to such small single-domain proteins offers the
      advantages of enhanced stability, and possibly access to a class of antigenic
      epitopes not generally recognised by conventional antibodies.

PMID- 11469384
TI  - A multi-modality assay platform for ultra-high throughput screening.
AB  - The demand for increased throughput during primary screening using less reagents
      is changing the way of drug discovery. Searching for hits using high throughput
      screening in 96-well format plates is being replaced by the use of higher density
      plates, such as 384 and 1536-well formats. The analysis of radiometric assays by
      scintillation counters is becoming limiting since only 12 wells can be counted at
      a time. Charged coupled device (CCD) camera based instruments, that image the
      whole plate in one exposure, speed up detection and are compatible with any
      microplate footprint. Researchers are also demanding a choice of detection
      methods, including fluorescence, luminescence and radioactivity, and require
      imagers suitable for all applications. LEADseeker Homogenous Imaging System is a
      multi-modality platform offering imaging technology and assay toolboxes for
      radiometric, fluorescent and luminescent based assays. LEADseeker allows the very
      rapid analysis of high density formats enabling ultra-high throughput screening
      of a range of biological assays. Research areas that can be studied using this
      system include enzyme assays, receptor binding and molecular interactions.

PMID- 11469385
TI  - Biopharmaceutical powders: particle formation and formulation considerations.
AB  - It is well known that protein/peptide-based drug formulations are more stable in
      the solid state than in the liquid state, thereby offering stability advantages
      in ambient temperature storage, product shipping/distribution, and long-term
      shelf life. Novel powder-based drug delivery systems recently emerging for
      applications in sustained release, inhalation, intradermal delivery, etc, add
      more value to protein solid dosage forms. Despite great research interests in
      understanding the drying effects on protein stability and a large collection of
      publications focusing on this area, systematic accounts of powder formation
      techniques are lacking. This review is to summarize a number of methods currently
      available for protein powder preparation. Some are common methods such as
      lyophilization, spray drying, pulverization, and precipitation, and some methods
      are more recently developed such as supercritical fluid precipitation, spray
      freeze drying, fluidized-bed spray coating and emulsion precipitation. In
      addition to examining the individual process effect on protein stability that is
      always the focus of formulation scientists, this review also likes to evaluate
      each method from a more practical sense in terms of process versatility and
      scalability. The conclusion is that each method has its own advantages and the
      use of a method is formulation and application specific. With the understanding
      of the principles and advantages of these methods, it can benefit our choice on
      selecting appropriate techniques for preparing a desired protein powder
      formulation for specific applications.

PMID- 11469386
TI  - Neonatal treatment with beta-cell stimulatory agents reduces the incidence of
      diabetes in BB rats.
AB  - The aim of the study was to investigate whether various beta-cell stimulatory
      drugs, given neonatally, influence the incidence of diabetes in BB rats. Newborn
      BB rats were treated twice daily for 6 days and diabetes development was observed
      during the following 200-day study period. Compared to a diabetes incidence of
      63.8% in 163 control BB rats which received saline or were untreated, the
      percentage of experimental BB rats that developed diabetes was as follows in the
      different subgroups: arginine-glucose: 47% (n = 73, p < 0.02); glucagon: 37% (n =
      93, p < 0.0001); tolbutamide-glucose: 36% (n = 58, p < 0.0005); and theophylline
      glucose: 39% (n = 41, p < 0.005). A long-term arginine-glucose treatment was not
      superior to the shorter neonatal treatment. Histological examination revealed a
      higher degree of insulitis in diabetic than in non-diabetic animals but no
      difference according to the kind of treatment was observed. Finally, we found
      that the diabetes incidence in BB rats was higher in the first litter compared to
      subsequent litters (p = 0.04). Thus, neonatal treatment with various beta-cell
      stimulatory agents reduces diabetes incidence in BB rats. The theory behind the
      study, that the treatment accelerates beta-cell maturation leading to increased
      immunological tolerance towards beta cells, is discussed.

PMID- 11469387
TI  - Glomerular basement membrane selective permeability in short-term streptozotocin
      induced diabetic rats.
AB  - In diabetes, the glomerular basement membrane undergoes thickening and structural
      alterations with loss of glomerular permselectivity properties. However, the
      onset of the alterations at early phases of diabetes is unclear. Aiming to
      determine the functional and structural alterations of the glomerular wall in the
      early stages of diabetes, we have studied the distribution of endogenous
      circulating albumin and type IV collagen in the glomerular basement membrane,
      using the immunocytochemical approach. The streptozotocin-injected hyperglycemic
      rat was our animal model. Renal tissues were examined after 10 days, 2, 4 and 6
      months of hyperglycemia. Upon immunogold labelings, changes in the glomerular
      permeability to endogenous albumin were found altered as early as upon ten days
      of hyperglycemia. In contrast, no structural modifications were detected at this
      time point. Indeed, glomerular basement membrane thickening and an altered type
      IV collagen labeling distribution were only observed after four months of
      hyperglycemia, suggesting that functional alterations take place early in
      diabetes prior to any structural modification. In order to evaluate the
      reversibility of the glomerular alterations, two-month-old diabetic animals were
      treated with insulin. These animals showed a significant restoring of their
      glomerular permselectivity. Our results suggest a link between glycemic levels
      and alteration of glomerular permeability in early stages of diabetes, probably
      through high levels of glycated serum proteins.

PMID- 11469388
TI  - PROLACTIN-deficiency in adult offspring of diabetic mothers.
AB  - Maternal diabetes induces fetal alterations, resulting in lasting consequences
      for the glucose tolerance of the offspring over several generations. In our
      experimental rat model, circulating prolactin, oestradiol, progesterone and
      corticosterone levels, known to influence insulin secretion and action, are
      determined in plasma of female adult offspring of mildly and severely diabetic
      mothers. Prolactin and progesterone levels are equally low in both groups as
      compared to controls, stressing the involvement of the CNS in the transgeneration
      effect; oestradiol and corticosterone levels are normal. No correlation is found
      between these hormonal alterations and the known differences in glucose
      tolerance.

PMID- 11469389
TI  - Octreotide, a somatostatin analogue, fails to inhibit hypoxia-induced retinal
      neovascularization in the neonatal rat.
AB  - OBJECTIVE: Octreotide, a somatostatin analogue, has been shown to prevent
      angiogenesis in diverse in vitro models. We evaluated its effect on retinal
      neovascularization in vivo, using a neonatal rat retinopathy model. METHODS: We
      used, on alternating days, hypoxia (10% O2) and hyperoxia (50% O2) during the
      first 14 days of neonatal rats, to induce retinal neovascularization. Half of the
      rats were injected subcutaneously with octreotide 0.7 microg/g BW twice daily. At
      day 18 the eyes were evaluated for the presence of epiretinal and vitreal
      hemorrhage, neovascularization and epiretinal proliferation. Octreotide
      pharmacokinetics and its effect on serum growth hormone (GH) and insulin-like
      growth factor I (IGF-I) were examined in 28 rats. RESULTS: Serum octreotide
      levels were 667 microg/l two hours after injection, 26.4 microg/l after nine
      hours and 3.2 microg/l after 14 hours. GH levels were decreased by 40% (p =
      0.002) two hours after injection but thereafter returned to baseline. IGF-I
      levels were unchanged two hours after injection and were elevated by 26% 14 hours
      after injection (p = 0.02). Epiretinal membranes were highly associated with
      epiretinal hemorrhages (p < 0.001), while retinal neovascularization was notably
      associated with vitreal hemorrhages (p < 0.001). CONCLUSIONS: Twice-daily
      injections of octreotide failed to produce sustained decrease in serum GH, but
      produced rebound elevation of serum IGF-I. Accordingly, no statistically
      significant effect of injections on retinal pathology was noted. This finding,
      however, does not contradict our assumption that GH suppression may decrease the
      severity of retinopathy.

PMID- 11469390
TI  - Pentoxifylline effects on nerve conduction velocity and blood flow in diabetic
      rats.
AB  - Pentoxifylline has several actions that improve blood rheology and tissue
      perfusion and may therefore potentially be applicable to diabetic neuropathy. The
      aims of this study were to ascertain whether 2 weeks of treatment with
      pentoxifylline could correct nerve conduction velocity and blood flow deficits in
      6-week streptozotocin-diabetic rats and to examine whether the effects were
      blocked by co-treatment with the cyclooxygenase inhibitor, flurbiprofen, or the
      nitric oxide synthase inhibitor, NG-nitro-L-arginine. Diabetic deficits in
      sciatic motor and saphenous sensory nerve conduction velocity were 56.5% and
      69.8% corrected, respectively, with pentoxifylline treatment. Sciatic endoneurial
      blood flow was approximately halved by diabetes and this deficit was 50.4%
      corrected by pentoxifylline. Flurbiprofen co-treatment markedly attenuated these
      actions of pentoxifylline on nerve conduction and blood flow whereas NG-nitro-L
      arginine was without effect. Thus, pentoxifylline treatment confers neurovascular
      benefits in experimental diabetic neuropathy, which are linked at least in part
      to cyclooxygenase-mediated metabolism.

PMID- 11469391
TI  - The effect of the removal of the area postrema on insulin and IGF-1-induced
      cardiovascular and sympathetic nervous responses.
AB  - Previous studies have demonstrated that insulin and IGF-1 both increase lumbar
      sympathetic nerve activity (LSNA) and decrease mean arterial pressure (MAP). We
      hypothesized that the peripheral responses to insulin and IGF-1 are mediated, at
      least in part, via the central nervous system. In this study we determined the
      effects of the peripheral administration of both insulin and IGF-1 on
      cardiovascular dynamics and LSNA following removal of the area postrema (APX), a
      major site of blood-brain communication. Insulin infusion in normal rats
      decreased MAP but increased HR and LSNA. When insulin was infused in APX rats it
      also decreased the MAP but the MAP recovered rapidly and plateaued at a level
      equivalent to normals after 40 min. Insulin significantly increased the HR and
      LSNA in the APX rats compared to normals. However, when hypoglycemia was
      prevented by glucose infusion, the HR and LSNA responses to insulin in the APX
      rats were similar to normals. IGF-1 also decreased MAP and to a greater extent in
      the APX rats compared to normals but the increased LSNA in APX rats was
      equivalent to normals. The APX rats when compared to normals had a greater
      sensitivity to insulin-induced hypoglycemia while IGF-1 decreased the plasma
      glucose to a lesser degree in APX rats. We conclude that insulin and IGF-1 entry
      into the CNS at least via the area postrema does not contribute significantly to
      the hypotensive response and that the greater depressor response to IGF-1 is
      likely due to enhanced vascular sensitivity in APX rats. The increased HR and
      LSNA following insulin were likely mediated by an increased reflexive response to
      hypoglycemia.

PMID- 11469392
TI  - High glucose-enhanced acetylcholine stimulated CGMP masks impaired vascular
      reactivity in tail arteries from short-term hyperglycemic rats.
AB  - Impaired vascular endothelium-dependent relaxation and augmented contractile
      responses have been reported in several models of long-term hyperglycemia.
      However, the effects of short-term ambient hyperglycemia are poorly understood.
      Since oxidative stress has been implicated as a contributor to impaired vascular
      function, we investigated the following: AIMS: (1) the effects of high glucose
      exposure in vitro (7-10 days) on vascular relaxation to acetylcholine (Ach) and
      contractility to norepinephrine (NE) and KCl; (2) if NO-dependent cGMP generation
      is affected under these conditions; and (3) aortic redox status. METHODS: Non
      diabetic rat tail artery rings were incubated in normal (5mM) (control NG) or
      high (20 mM) glucose buffer (control HG). Vascular responses to Ach, NE and KCl
      were compared to those of streptozotocin (SZ) diabetic animals in the same
      buffers (diabetic NG, diabetic HG). Ach-stimulated cGMP levels were quantitated
      as an indirect assessment of endothelial nitric oxide (NO) production and
      oxidative stress evaluated by measuring vascular glutathione and oxidized
      glutathione. RESULTS: Rings from diabetic rats in NG showed impaired relaxation
      to Ach (P = 0.002) but relaxed normally, when maintained in HG. Similarly,
      contractile responses to NE were attenuated in diabetic rings in NG but similar
      to controls in HG. HG markedly augmented maximal contraction to KCl compared to
      control and diabetic vessels in NG (P < 0.0001). Diabetic vessels in a
      hyperosmolar, but normoglycemic, milieu respond like those in HG. In vitro, HG
      for 2 hours changed neither relaxation nor contractile responses to NE and KCl in
      control rings. Basal cGMP levels were lower in aortae from diabetic animals pre
      incubated in NG than in HG/LG or in control rings in NG (P < 0.05). cGMP
      responses to Ach were exaggerated in diabetic vessels in HG (P = 0.035 vs.
      control NG, P = 0.043 vs. diabetic NG) but not different between control and
      diabetic rings in NG. Vessels from diabetic animals had lower levels of GISH (P <
      0.0001) and higher levels of GSSG (P < 0.0001) indicating oxidative stress.
      CONCLUSIONS: Our data indicate that endothelium-dependent relaxation is altered
      early in the diabetic state and that increased NO responses may compensate for
      augmented oxidative stress but the lack of effect of short-term exposure of
      normal vessels to HG suggests that short-term hyperglycemia per se does not cause
      abnormal vascular responses.

PMID- 11469393
TI  - Changes in the growth hormone-IGF-I axis in non-obese diabetic mice.
AB  - We investigated the changes in GH-IGF-I axis in non-obese diabetic (NOD)-mice, a
      model of insulin-dependent diabetes mellitus. Diabetic female NOD mice and their
      age- and sex-matched controls were sacrificed at 4, 14, 21 and 30 days (30d DM)
      after the onset of glycosuria. Serum GH levels increased and serum IGF-I levels
      decreased in the 30d DM group (182 +/- 32% and 45 +/- 24% of age-matched controls
      respectively, p < 0.05). Another group (30d DM + I) was given SC insulin, and its
      serum IGF-I levels remained decreased. Liver GH receptor (GHR) and GH binding
      protein (GHBP) mRNA levels, as well as liver membrane GH binding assays were
      deeply decreased in the 30d DM group in comparison to controls. GHR message and
      binding capacity remained decreased in the 30d DM + I group. Renal GHR mRNA was
      decreased at 21d DM but not at 14d DM, whereas GHBP mRNA remained unchanged
      throughout the experiment. In conclusion, increased serum GH levels are
      documented in NOD diabetic mice, similarly to the changes described in humans.
      The decrease in GHR levels and decreased serum IGF-I in spite of increased
      circulating GH suggest a state of GH resistance.

PMID- 11469394
TI  - Inhibitory effect of diabetes on proliferation of vascular smooth muscle after
      balloon injury in rat aorta.
AB  - The effect of streptozotocin-induced diabetes on cell proliferation in rat aortic
      intima-media, as well as on local gene expression of transforming growth factor
      beta1 (TGF-beta1) was studied. TGF-beta1 mRNA was measured by solution
      hybridization and TGF-beta1 protein by ELISA. Proliferation was measured by
      bromodeoxyuridine incorporation into DNA two days after balloon injury. All BrdU
      labelled cells observed were smooth muscle cells. After a diabetes duration of 2
      and 4 weeks, labelled cells were significantly fewer compared with controls.
      Circulating levels of total TGF-beta1 were lowered in rats with 2 weeks diabetes.
      Although the balloon injury procedure by itself stimulated the gene expression of
      TGF-beta1, no significant difference in TGF-beta1 mRNA content between diabetic
      and control rats after injury was found. IN CONCLUSION: vascular smooth muscle
      proliferation in vivo is inhibited by the diabetic state in this model of insulin
      deficient diabetes and this inhibition is not related to an impaired local
      expression of TGF-beta1.

PMID- 11469395
TI  - Aminoguanidine exerts a beta-cell function-preserving effect in high glucose
      cultured beta-cells (INS-1).
AB  - We investigated the effects of aminoguanidine (AG) on beta-cell functions in an
      insulin secreting cell line (INS-1). Culture with 27mM glucose for one week
      markedly decreased both insulin release and insulin content compared to culture
      in 0.8 mM or 3.3 mM glucose. Relative to culture at 27 mM glucose alone, the co
      exposure to 1 mM AG almost doubled basal as well as glucose or 25 mM KCl
      stimulated insulin release and increased insulin content by 42%. AG failed to
      affect release and content in cells cultured at 0.8 or 3.3 mM glucose.
      Preproinsulin mRNA content in 27mM glucose-cultured cells was 52% suppressed
      compared to 0.8mM glucose-cultured cells, and AG treatment partially counteracted
      this decline. Advanced glycosylation end product (AGE)-associated fluorescence
      (370nm excitation and 440 nm emission) of cells' extracts did not differ between
      27mM and 0.8mM glucose-cultured cells after 1 week of culture and fluorescence
      was unaffected by AG. Accumulation of nitrite into culture media was markedly
      increased from 27mM glucose-cultured cells, and this accumulation was 33%
      suppressed by AG. In conclusion, AG partially protects against glucotoxic effects
      in INS-1 cells. These beneficial effects may involve a decrease in early
      glycation products and/or nitric oxide synthase (NOS) activity. The effects which
      were obtained after one week of high glucose exposure may supplement AGE
      associated effects seen after chronically elevated glucose.

PMID- 11469396
TI  - Feeding a protective hydrolysed casein diet to young diabetic-prone BB rats
      affects oxidation of L[U-14C]glutamine in islets and Peyer's patches, reduces
      abnormally high mitotic activity in mesenteric lymph nodes, enhances islet
      insulin and tends to normalize NO production.
AB  - The present studies were undertaken to examine concomitant diet-induced changes
      in pancreatic islets and cells of the gut immune system of diabetes-prone BB rats
      in the period before classic insulitis. Diabetes-prone (BBdp) and control
      nondiabetes prone (BBc) BB rats were fed for approximately 17 days either a
      mainly plant-based standard laboratory rodent diet associated with high diabetes
      frequency, NIH-07 (NIH) or a protective semipurified diet with hydrolyzed casein
      (HC) as the amino acid source. By about 7 weeks of age, NIH-fed BBdp rats had
      lower plasma insulin and insulin/glucose ratio, lower insulin content of isolated
      islets, lower basal levels of NO but higher responsiveness of NO production to IL
      1beta in cultured islets, and higher Con A response and biosynthetic activities
      in mesenteric lymphocytes than control rats fed the same diet. In control rats,
      the HC diet caused only minor changes in most variables, except for a decrease in
      oxidation of L-[U-14C]glutamine in Peyer's patch (PP) cells and an increase in
      protein biosynthesis in mesenteric lymphocytes. In BBdp rats, however, the HC
      diet increased plasma insulin concentration, islet insulin/protein ratio, and
      tended to normalize the basal and IL-1beta-stimulated NO production by cultured
      islets. The HC diet decreased oxidation of L[U-14C]glutamine in BBdp pancreatic
      islets, whereas oxidation of L-[U-14C]glutamine in PP cells was increased, and
      the basal [Methyl-3H]thymidine incorporation in mesenteric lymphocytes was
      decreased. These findings are compatible with the view that alteration of
      nutrient catabolism in islet cells as well as key cells of the gut immune system,
      particularly changes in mitotic and biosynthetic activities in mesenteric
      lymphocytes, as well as basal and IL-1beta stimulated NO production, participate
      in the sequence of events leading to autoimmune diabetes in BB rats. Thus, the
      protection afforded by feeding a hydrolysed casein-based diet derives from
      alterations in both the target islet tissue and key cells of the gut immune
      system in this animal model of type 1 diabetes.

PMID- 11469397
TI  - Slowing of motor nerve conduction velocity in streptozotocin-induced diabetic
      rats is preceded by impaired vasodilation in arterioles that overlie the sciatic
      nerve.
AB  - Diabetes mellitus produces marked abnormalities in motor nerve conduction, but
      the mechanism is not clear. In the present study we hypothesized that in the
      streptozotocin (STZ)-induced diabetic rat impaired vasodilator function in
      arterioles that provide circulation to the region of the sciatic nerve is
      associated with reduced endoneural blood flow (EBF) and that these defects
      precede slowing of motor nerve conduction velocity, and thereby may contribute to
      nerve dysfunction. As early as three days after the induction of diabetes
      endoneural blood flow was reduced in the STZ-induced diabetic rat. Furthermore,
      after 1 week of diabetes acetylcholine-induced vasodilation was found to be
      impaired. This was accompanied by an increase in the superoxide level in
      arterioles that provide circulation to the region of the sciatic nerve as well as
      changes in the level of other markers of oxidative stress including an increase
      in serum levels of thiobarbituric acid reactive substances and a decrease in lens
      glutathione level. In contrast to the vascular related changes that occur within
      1 week of diabetes, motor nerve conduction velocity and sciatic nerve Na+/K+
      ATPase activity were significantly reduced following 2 and 4 weeks of diabetes,
      respectively. These studies demonstrate that changes in vascular function in the
      STZ-induced diabetic rat precede the slowing of motor nerve conduction velocity
      (MNCV) and are accompanied by an increase in superoxide levels in arterioles that
      provide circulation to the region of the sciatic nerve.

PMID- 11469398
TI  - Impaired relaxation in aorta from streptozotocin-diabetic rats: effect of
      aminoguanidine (AMNG) treatment.
AB  - AIM: The effect of 8 weeks' streptozotocin (STZ)-induced diabetes and
      aminoguanidine (AMNG), the inhibitor of advanced glycosylation reaction,
      treatment on arteriolar reactivity to vasoactive substances was investigated in
      vitro. MATERIALS AND METHODS: Studies were performed in untreated control rats
      (n=10), STZ-induced (60 mg/kg i.v.) diabetic rats (n=10), AMNG-treated (600mg/l
      given in drinking water throughout 8 weeks) control rats (n=10) and AMNG-treated
      (600mg/l given in drinking water, beginning at 72h after STZ and throughout 8
      weeks of diabetes) diabetic rats (n=10). Results are expressed as the mean +/
      s.e. Relaxant responses are expressed as a percentage (%) relaxation of
      noradrenaline-induced tone. Statistical comparisons were made by one-way analysis
      of variance (ANOVA) followed by Tukey-Kramer multiple comparisons test. RESULTS:
      1. The decreased body weights (205 +/- 6g) and increased blood glucose levels
      (583 +/- 8 mg/dl) of diabetic rats were partially restored by treatment of
      aminoguanidine (253 +/- 6 g, p < 0.05 and 480 +/- 14 mg/ dl, p < 0.001,
      respectively). 2. Diabetes caused a 71% deficit in maximal endothelium-dependent
      relaxation to acetylcholine for noradrenaline precontracted aortas (p<0.001).
      AMNG treatment prevented the diabetes-induced impairment in endothelium dependent
      relaxation (58 +/- 8%) to acetylcholine, maximum relaxation remaining in the non
      diabetic range (78 +/- 4%). 3. Neither diabetes nor treatment affected
      endothelium-independent relaxation (pD2 and max. Relax.) to sodium nitroprusside.
      4. Vasoconstrictor responses (pD2 and Max. Contraction) to noradrenaline and KCl
      were not influenced by the diabetic state and treatment. CONCLUSION: Our data
      suggest that 8 weeks of experimental diabetes is associated with a decreased
      endothelium-dependent vasodilatation. AMNG treatment may prevent diabetes-induced
      endothelial dysfunction. This may be mediated via the prevention of advanced
      glycosylation end product formation, the enhanced release of vasodilator
      substances such as prostacyclin, the increased elasticity of blood vessels, the
      antioxidant activity and inhibitor activity of enzyme aldose-reductase by AMNG.

PMID- 11469399
TI  - D-glucose stimulates the Na+/K+ pump in mouse pancreatic islet cells.
AB  - To determine the effect of D-glucose on the beta-cell Na+/K+ pump, 86Rb+ influx
      was studied in isolated, -cell-rich islets of Umea-ob/ob mice in the absence or
      presence of 1mM ouabain. D-glucose (20mM) stimulated the ouabain-sensitive
      portion of 86Rb+ influx by 65%, whereas the ouabain-resistant portion was
      inhibited by 48%. The Na+/K+ ATPase activity in homogenates of islets of Umea
      ob/ob mice or normal mice was determined to search for direct effects of D
      glucose. Thus, ouabain-sensitive ATP hydrolysis in islet homogenates was measured
      in the presence of different D-glucose concentrations. No effect of D-glucose (3
      20mM) was observed in either ob/ob or normal islets at the optimal Na+/K+ ratio
      for the enzyme (135mM Na+ and 20mM K+). Neither D-glucose (3-20mM) nor L-glucose
      or 3-O-methyl-D-glucose (20mM) affected the enzyme activity at a high Na+/K+
      ratio (175 mM Na+ and 0.7 mM K+). Diphenylhydantoin (150 microM) decreased the
      enzyme activity at optimal Na+/K+ ratio, whereas 50 microM of the drug had no
      effect. The results suggest that D-glucose induces a net stimulation the Na+/K+
      pump of beta-cells in intact islets and that D-glucose does not exert any direct
      effect on the Na+/K+ ATPase activity.

PMID- 11469400
TI  - Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans
      with type 2 diabetes.
AB  - We have screened a subtracted cDNA library in order to identify differentially
      expressed genes in omental adipose tissue of human patients with Type 2 diabetes.
      One clone (#1738) showed a marked reduction in omental adipose tissue from
      patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738
      was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ,
      GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in
      cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed
      that apM1 mRNA levels were significantly reduced in omental adipose tissue of
      obese patients with Type 2 diabetes compared with lean and obese normoglycemic
      subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous
      adipose tissue of Type 2 diabetic patients. Whereas the biological function of
      apM1 is presently unknown, the tissue specific expression, structural
      similarities to TNFalpha, and the dysregulated expression observed in obese Type
      2 diabetic patients suggest that this factor may play a role in the pathogenesis
      of insulin resistance and Type 2 diabetes.

PMID- 11469401
TI  - A new spontaneously diabetic non-obese Torii rat strain with severe ocular
      complications.
AB  - A new spontaneously diabetic strain of the Sprague-Dawley rat was established in
      1997 and named the SDT (Spontaneously Diabetic Torii) rat. In this research, we
      investigated the characteristics of the disease condition in the SDT rats. The
      time of onset of glucosuria was different between male and female SDT rats;
      glucosuria appeared at approximately 20 weeks of age in male rats and at
      approximately 45 weeks of age in female rats. A cumulative incidence of diabetes
      of 100% was noted by 40 weeks of age in male rats, while it was only 33.3% even
      by 65 weeks of age in female rats. The survival rate up to 65 weeks of age was
      92.9% in male rats and 97.4% in female rats. Glucose intolerance was observed in
      male rats from 16 weeks of age. The clinical characteristics of the male SDT rats
      were (1) hyperglycemia and hypoinsulinemia (from 25 weeks of age); (2) long-term
      survival without insulin treatment; (3) hypertriglyceridemia (by 35 weeks of
      age); however, no obesity was noted in any of the male rats. The
      histopathological characteristics of the male rats with diabetes mellitus (DM)
      were (1) fibrosis of the pancreatic islets (by 25 weeks of age); (2) cataract (by
      40 weeks of age); (3) tractional retinal detachment with fibrous proliferation
      (by 70 weeks of age) and (4) massive hemorrhaging in the anterior chamber (by 77
      weeks of age). These clinical and histopathological characteristics of the
      disease in SDT rats resemble those of human Type 2 diabetes with insulin
      hyposecretion. In conclusion, SDT rat is considered to be a potentially useful
      model for studies of diabetic retinopathy encountered in humans.

PMID- 11469402
TI  - High-resolution elemental mapping of titanium oxide/aluminium oxide multilayer by
      spectrum-imaging.
AB  - A spectrum-imaging technique based on scanning transmission electron microscopy
      combined with an electron energy-loss spectroscopy has been applied for the
      multilayer of amorphous titanium oxide and aluminium oxide layers on silicon
      substrate. We demonstrate the high-resolution elemental mapping and discuss the
      advantage of this method compared to an energy-filtering transmission electron
      microscopy. The main advantage is the absence of chromatic broadening, which
      allows the use of a large collection angle to acquire spectrum-image data and a
      wide energy window to integrate the core-loss signals. This suggests that the
      spatial resolution of elemental maps is mainly determined by the size of the
      electron probe.

PMID- 11469403
TI  - STEM imaging with a thin annular detector.
AB  - In scanning transmission electron microscopy, the use of a thin annular detector
      (TAD), with a ratio of outer to inner radii of about 1.1, allows the selective
      imaging of various components of a specimen so that different crystalline or
      amorphous phases may be distinguished. The range of scattering angles to be
      selected can be varied by using post-specimen lenses to magnify the diffraction
      pattern of the object. Marginal image modes, giving differentiated images, and
      ultra-high resolution bright-field images may be obtained when the central spot
      of the diffraction pattern is magnified so that its radius approximates the inner
      radius of the TAD. Consideration of the relationship of the TAD imaging to the
      form of the nanodiffraction pattern obtainable from any small area of the
      specimen shows that TAD imaging is equivalent to 'variable coherence imaging' and
      may be used in the determination of medium-range ordering in amorphous or
      disordered materials.

PMID- 11469404
TI  - New scheme for calculation of annular dark-field STEM image including both
      elastically diffracted and TDS waves.
AB  - A new scheme of calculation of high-angle annular dark-field STEM image, capable
      of including both elastically diffracted and thermal diffuse scattering waves,
      has been presented by a combination of Pennycook's and Nakamura's methods. The
      new scheme has been demonstrated for image simulations of Si(011) as functions of
      thickness, defocus values and detector angles. In the present method, the TDS
      electron intensities are treated in the same way as in Pennycook's method, having
      a clear physical picture of its origin and reflecting the atom configuration in
      the systems. For the case of Si(011), it has been confirmed that at the detector
      angle of 60 to 160 mrad, which is usually applied, the image becomes highly
      incoherent, and even the image formed only from SOLZ beams becomes incoherent at
      the detector angle. At a low detector angle, however, the image has coherent
      features indicating the necessity of a simulation for individual systems.

PMID- 11469405
TI  - An auto-tuning method for focusing and astigmatism correction in HAADF-STEM,
      based on the image contrast transfer function.
AB  - An auto-tuning method for high-angle annular detector dark field scanning
      transmission electron microscopy (HAADF-STEM) is proposed which corrects the
      defocus to the optimum Scherzer focus and compensates the astigmatism. Because
      the method is based on the image contrast transfer function formulated for the
      HAADF-STEM, the defocus and the astigmatism are accurately measured from input of
      two different defocus images. The method is designed to work independent of
      object function in the linear imaging model by analysing the spectral ratio
      between two Fourier spectra of their images, which is useful for cases where the
      spectrum of object function is not uniformly spread out over the reciprocal
      space. The method was preliminarily tested in a Hitachi HD-2000 STEM, and
      successful results of the auto-tunings from the viewpoint of verification of the
      algorithm were obtained using general specimens of Au fine particles and a thin
      section of a semiconductor device.

PMID- 11469406
TI  - Progress in aberration-corrected scanning transmission electron microscopy.
AB  - A new corrector of spherical aberration (C(S)) for a dedicated scanning
      transmission electron microscope (STEM) is described and its results are
      presented. The corrector uses strong octupoles and increases C(C) by only 0.2 mm
      relative to the uncorrected microscope. Its overall stability is greatly improved
      compared to our previous design. It has achieved a point-to-point resolution of
      1.23 A in high-angle annular dark field images at 100 kV. It has also increased
      the current available in a 1.3 A-sized probe by about a factor of ten compared to
      existing STEMs. Its operation is greatly assisted by newly developed autotuning
      software which measures all the aberration coefficients up to fifth order in less
      than one minute. We conclude by discussing the present limits of aberration
      corrected STEM, and likely future developments.

PMID- 11469407
TI  - Ho arrangement in the Zn6Mg3Ho icosahedral quasicrystal studied by atomic
      resolution Z-contrast STEM.
AB  - The atomic structure of the Zn6Mg3Ho icosahedral quasicrystal has been studied by
      high-angle annular dark-field scanning transmission electron microscopy (HAADF
      STEM) with Z-contrast (Z: atomic number). We demonstrate that in particular Z
      contrast imaging is quite powerful for specifying heavy atom positions in the
      quasicrystalline compound, as shown by a comparison with high-resolution phase
      contrast imaging. It is confirmed that the observed Z-contrast images are fairly
      well explained by the projected potential of only the Ho atomic arrangement,
      which was recently proposed by X-ray diffraction analysis; Ho occupies an even
      body-center site of the 3-dimensional Penrose lattice. Consequently, the present
      direct structural observation strongly supports the validity of the proposed Ho
      site.

PMID- 11469408
TI  - Structural study of an Al73Ni22Fe5 decagonal quasicrystal by high-angle annular
      dark-field scanning transmission electron microscopy.
AB  - A water-quenched Al73Ni22Fe5 decagonal quasicrystal was investigated by the
      selected-area electron diffraction, convergent-beam electron diffraction and high
      angle annular dark-field scanning transmission electron microscope methods. The
      alloy shows very sharp spots and nearly no diffuse scattering in the diffraction
      patterns, belongs to centrosymmetric space group P10(5)/mmc and is constructed
      almost by one type of 2 nm diameter atom cluster having mirror symmetry with a
      highly quasicrystalline order arrangement. Although a small number of 2 nm atom
      clusters having five-fold symmetry exists, which are similar to those observed in
      melt-quenched Al70Ni15Fe15, the structure of Al73Ni22Fe5 is considered to
      basically be the same as that of water-quenched Al72Ni20Co8, which is constructed
      only by mirror symmetry clusters arranged with a very high quasiperiodicity. The
      number of valence electrons per atom (e/a) of the present alloy (1.92) is very
      close to that of Al72Ni20Co8 (1.90), but differs from those of phases constructed
      by only the five-fold symmetry clusters. This implies that these alloys are Hume
      Rothery electron compounds, whose structures are determined primarily by e/a
      value.

PMID- 11469409
TI  - Application of atomic scale STEM techniques to the study of interfaces and
      defects in materials.
AB  - Incoherent imaging and analysis techniques in the scanning transmission electron
      microscope (STEM) provide the potential to map changes in structure, composition
      and bonding that occur at materials interfaces and defects on the fundamental
      atomic scale. Such comprehensive characterization capabilities permit a detailed
      analysis of the structure-property relationships of interfaces and defects to be
      performed. In this paper, we discuss the resolution limits of such techniques in
      the JEOL 2010F STEM/TEM operating both under standard conditions and at elevated
      temperatures. Examples of the use of such techniques to quantify the atomic scale
      defect chemistry at interfaces and defects in perovskite oxides, the growth and
      structure of II-VI and III-V quantum dots and the electronic structure of
      threading dislocations in GaN will also be presented.

PMID- 11469410
TI  - Optimizing the environment for sub-0.2 nm scanning transmission electron
      microscopy.
AB  - Sub-0.2 nm probes can now be readily obtained on Schottky field-emission
      microscopes. However, environmental instabilities are proving to be the limiting
      factors for atomic resolution spectroscopy and distortion-free annular-dark field
      imaging. This is a result of the long acquisition times and the serial nature of
      the scanning system where instabilities result in image distortions rather than
      reductions in contrast. Troubleshooting the most common environmental problems is
      discussed here. In addition to the expected sensitivity to mechanical vibration,
      electromagnetic interference and temperature variations, air-pressure
      fluctuations are found to have a significant impact on microscopes with side
      entry goiniometers.

PMID- 11469411
TI  - On the origin of transverse incoherence in Z-contrast STEM.
AB  - We use a Bloch wave approach to further investigate the origins of the incoherent
      nature of Z-contrast imaging using an ADF detector in a STEM. We discuss how,
      although at high angles the collected electrons will be mostly thermally
      scattered in addition to the elastic scattering, it is not the thermal scattering
      that destroys the coherence, rather the combination of the large detector with
      the high-angle elastic scattering. This incoherent nature of the elastic
      scattering arises through the filtering of the 1s-type Bloch states by the
      detector geometry. We show that it is this filtering that renders an atomic
      column an independent scatterer insensitive to the configuration of neighbouring
      columns. It also makes the image contrast insensitive to the effects of beam
      spreading onto neighbouring columns as the probe propagates through the crystal.
      We also discuss the implications of this for previous calculations of the
      intensity of Z-contrast images.

PMID- 11469412
TI  - Three-dimensional STEM for observing nanostructures.
AB  - A new scanning transmission electron microscope has been developed for three
      dimensional (3D) observations of nanostructures. Using double spherical fulcra,
      accurate eucentric rotation was achieved. Cylindrical specimens for 3D
      observation were prepared by a microsampling technique using a focused ion beam.
      Copper via-holes of a semiconductor memory device and ZnO particles were observed
      by the 3D-STEM from different directions, and 3D-data of the ZnO particles were
      successfully reconstructed in a topography mode.

PMID- 11469413
TI  - Temperature dependency of radiation damage in inorganic materials by 300 keV
      electrons.
AB  - Temperature dependency of radiation damage in albite and natrolite was studied
      quantitatively by measuring the diffraction intensity with imaging plates.
      Radiation damage was reduced at low temperature in albite but was enhanced in
      natrolite. A damage process model, in which creation and annihilation of
      localized defects were considered, was proposed. According to this model,
      Boltzmann factor in temperature dependency is dominated by a difference between
      energy for diffusion of the localized defects and energy for breakdown of a
      crystal framework. When the diffusion energy is larger than breakdown energy, the
      activation energy in Boltzmann factor seems to be effectively negative.

PMID- 11469414
TI  - Nanocrystal formation in hexagonal SiC after Ge+ ion implantation.
AB  - High-resolution and analytical electron microscopy techniques are used to
      characterize Ge-implanted hexagonal SiC. After annealing the implanted samples at
      1200 degrees C, Ge is found to be located preferentially on interstitial sites.
      After annealing at 1600 degrees C, small nanocrystals of strained cubic and
      hexagonal (or faulted cubic) Ge and Ge Si form. Occasionally, hexagonal (or
      faulted cubic) Si nanocrystals are observed also.

PMID- 11469415
TI  - Structural imperfection of beta-Si3N4 crystals associated with nucleation.

PMID- 11469416
TI  - Real-time observation of spherical aberration-free phase image using high-speed
      image processing CCD video camera.
AB  - Spherical aberration-free phase images have been observed at a time resolution of
      1/30 s for the first time by using a defocus-image modulation processing electron
      microscope (DIMP-EM) combined with a newly developed high-speed image processing
      CCD video camera. In a profile image of the Au (011) crystal surface, no extra
      interference fringes were observed outside the crystal region, which clearly
      demonstrates successful correction of spherical aberration in real-time. The
      novel real-time DIMP-EM enabled the dynamic observation of surface and interface
      phenomena at an atomic level.

PMID- 11469417
TI  - Early morphological changes in the rat soleus muscle induced by tenotomy and
      denervation.
AB  - Early morphological changes of the rat soleus muscle induced by tenotomy were
      examined by scanning and thin-section electron microscopy. The potassium
      hydroxide (KOH) and collagenase treatment was successfully used to remove
      extracellular materials and to examine the surface of muscle fibres with a
      scanning electron microscope. Morphological changes in the fibre surface appeared
      as early as 12 h after tenotomy, showing wrinkling of the sarcolemma in localized
      areas. At 24 h post-operative, transverse folds and grooves were conspicuous
      along the entire length of muscle fibres. Tenotomized muscles which were
      denervated simultaneously or within 24 h of tenotomy did not show any appreciable
      changes in the fibre surface. Thin-section electron microscopy revealed that the
      earliest change inside muscle fibres was the occurrence of focal or segmental
      areas of an irregular alignment of myofibrils representing myofibril
      disorganization with occasional disintegrated Z lines at 24 h after tenotomy.
      Segmental myofibril breakdown was occasionally found to extend obliquely from the
      fibre periphery to the central area. Such myofibril disorganization became more
      conspicuous along muscle fibres, especially in the central area, at 2 days after
      tenotomy, showing the loss of thick filaments within myofibrils and the
      disintegration of Z lines. Such myofibrillar disorganization can be correlated
      with the morphological changes in the fibre surface in view of the clinical
      implication.

PMID- 11469418
TI  - Endothelin system in human persistent and paroxysmal atrial fibrillation.
AB  - INTRODUCTION: Activation of the endothelin system is an important compensatory
      mechanism that is activated during left ventricular dysfunction. Whether this
      system plays a role at the atrial level during atrial fibrillation (AF) has not
      been examined in detail. The purpose of this study was to investigate mRNA and
      protein expression levels of the endothelin system in AF patients with and
      without concomitant underlying valve disease. METHODS AND RESULTS: Right atrial
      appendages of 36 patients with either paroxysmal or persistent AF were compared
      with 36 controls in sinus rhythm. The mRNA amounts of pro-endothelin-1 (pro-ET
      1), endothelin receptor A (ET-A), and endothelin receptor B (ET-B) were studied
      by semiquantitative polymerase chain reaction. Protein amounts of the receptors
      were investigated by slot-blot analysis. mRNA amounts of pro-ET-1 were increased
      (+40%; P = 0.002) only in AF patients with underlying valve disease. ET-A and ET
      B receptor protein amounts were significantly reduced in patients with paroxysmal
      AF (-39% and -47%, respectively) and persistent AF with underlying valve disease
      (-28% and -30%, respectively) and in persistent AF without valve disease (-20%
      and -40%, respectively). ET-A mRNA expression was unaltered in paroxysmal and
      persistent AF, whereas ET-B mRNA was reduced by 30% in persistent AF with (P <
      0.001) or without (P = 0.04) valve disease, but unchanged in paroxysmal AF.
      CONCLUSION: Substantial changes in gene expression of the endothelin system were
      observed in human atria during AF, especially in the presence of underlying valve
      disease. Alterations in endothelin expression associated with AF could play a
      role in the pathophysiology of AF and the progression of underlying heart
      disease.

PMID- 11469419
TI  - Endothelin: AF-riend or AF-oe?

PMID- 11469420
TI  - Intra-atrial conduction block along the mitral valve annulus during accessory
      pathway ablation: evidence for a left atrial "isthmus".
AB  - INTRODUCTION: We observed a change in the atrial activation sequence during
      radiofrequency (RF) energy application in patients undergoing left accessory
      pathway (AP) ablation. This occurred without damage to the AP and in the absence
      of a second AP or alternative arrhythmia mechanism. We hypothesized that block in
      a left atrial "isthmus" of tissue between the mitral annulus and a left inferior
      pulmonary vein was responsible for these findings. METHODS AND RESULTS:
      Electrophysiologic studies of 159 patients who underwent RF ablation of a left
      free-wall AP from 1995 to 1999 were reviewed. All studies with intra-atrial
      conduction block resulting from RF energy delivery were identified. Fluoroscopic
      catheter positions were reviewed. Intra-atrial conduction block was observed
      following RF delivery in 11 cases (6.9%). This was evidenced by a sudden change
      in retrograde left atrial activation sequence despite persistent and unaffected
      pathway conduction. In six patients, reversal of eccentric atrial excitation
      during orthodromic reciprocating tachycardia falsely suggested the presence of a
      second (septal) AP. A multipolar coronary sinus catheter in two patients directly
      demonstrated conduction block along the mitral annulus during tachycardia.
      CONCLUSION: An isthmus of conductive tissue is present in the low lateral left
      atrium of some individuals. Awareness of this structure may avoid
      misinterpretation of the electrogram during left AP ablation and may be useful in
      future therapies of atypical atrial flutter and fibrillation.

PMID- 11469421
TI  - Identification and catheter ablation of extracardiac and intracardiac components
      of ligament of Marshall tissue for treatment of paroxysmal atrial fibrillation.
AB  - INTRODUCTION: The ligament of Marshall is a left atrial neuromuscular bundle with
      sympathetic innervation that may be a source of atrial fibrillation (AF)-inducing
      automatic activity. METHODS AND RESULTS: Twenty-four patients with paroxysmal AF
      (including 18 with adrenergic AF) and 25 with other arrhythmias underwent
      catheter mapping. In cases of adrenergic AF, radiofrequency ablation was
      attempted when Marshall potentials were recorded. Patients were followed for 2
      months before and 11.2 +/- 4.2 months after the procedure. Catheterization of the
      distal superoposterior coronary sinus was feasible in 14 patients with AF (10
      with adrenergic AF) and 12 patients without AF. A discrete Marshall potential was
      recorded in 12 patients with AF versus 3 patients without AF (P = 0.004). In 10
      patients with adrenergic AF, this potential followed the atrial electrogram
      during sinus rhythm by 26 +/- 5 msec on left atrial recordings and 24 +/- 4 msec
      on coronary sinus recordings, and preceded it during atrial ectopy by 29 +/- 5
      msec and 26 +/- 5 msec, respectively. It was abolished by epicardial (n = 1),
      endocardial (n = 4), or combined epicardial and endocardial ablation (n = 5).
      Seven patients with ablation showed significant reductions in adrenergic AF,
      whereas no significant change was seen in 8 adrenergic AF patients not undergoing
      ablation (P = 0.004). No improvement was seen in 3 of 4 patients with only
      endocardial ablation, whereas all 6 patients with epicardial ablation improved (P
      = 0.033). CONCLUSION: Recording of Marshall potential is feasible in patients
      with paroxysmal AF. Combined epicardial and endocardial catheter ablation of
      ligament of Marshall tissue may reduce the paroxysms of adrenergic AF.

PMID- 11469422
TI  - Microvolt T wave alternans in human cardiac hypertrophy: electrical instability
      and abnormal myocardial arrangement.
AB  - INTRODUCTION: Although T wave alternans (TWA) is a promising risk marker for
      myocardial electrical instability, it remains unclear how the presence of TWA is
      related to myocardial damage. METHODS AND RESULTS: TWA was measured in 28
      patients with hypertrophic cardiomyopathy (HCM), 29 patients with hypertensive
      left ventricular hypertrophy (HLVH), and 15 normal volunteers using a CH2000
      system. The amplitude of TWA (Valt) was measured at the lead with the maximum
      amplitude. Cardiac biopsy was performed in 12 HCM patients, who were divided into
      two groups (severe and mild) based on histologic findings of myocardial disarray
      and fibrosis. TWA was positive (Valt > 1.9 microV) in 61% of HCM and 31% of HLVH,
      despite a nearly identical left ventricular mass index (176 +/- 65 g/m2 vs 175 +/
      39 g/m2). Valt at heart rate = 110 beats/min was significantly greater in HCM
      with severe disarray and fibrosis than in HCM with mild disarray and in HLVH.
      CONCLUSION: In HCM patients, a positive TWA test probably is related to abnormal
      myocardial arrangement (disarray) and/or fibrosis, and it may reflect electrical
      instability of the myocardium.

PMID- 11469423
TI  - Repolarization alternans facilitated by structural abnormalities of the heart:
      another piece of the puzzle.

PMID- 11469424
TI  - VERDICT: the Verapamil versus Digoxin Cardioversion Trial: A randomized study on
      the role of calcium lowering for maintenance of sinus rhythm after cardioversion
      of persistent atrial fibrillation.
AB  - INTRODUCTION: Many relapses of atrial fibrillation (AF) occur, especially during
      the first week(s) after electrical cardioversion (ECV). The aim of the present
      study was to compare in a randomized design the efficacy of verapamil
      (intracellular calcium lowering) versus digoxin (calcium increasing) for
      maintenance of sinus rhythm after ECV. METHODS AND RESULTS: Ninety-seven patients
      with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for
      1 month before and 1 month after ECV. The first month after ECV, patients
      recorded heart rhythm using daily transtelephonic monitoring. No additional
      antiarrhythmic drugs were given. Of the 97 patients, 43 patients (20 verapamil)
      underwent ECV per protocol. Median previous AF duration was 18 and 26 days for
      verapamil and digoxin, respectively. There were no differences in atrial
      dimensions and underlying heart disease between the two groups. The success rate
      of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had
      recurrence of AF. Median time to recurrence was 5 days (range 0 to 26) versus 8
      days (range 2 to 28) (P = NS), respectively. CONCLUSION: Stand-alone
      intracellular calcium lowering by verapamil around ECV does not enhance
      cardioversion outcome.

PMID- 11469425
TI  - Calcium channel blockade for prevention of recurrent atrial fibrillation: have we
      reached a VERDICT?

PMID- 11469426
TI  - Repolarization abnormalities detected by magnetocardiography in patients with
      dilated cardiomyopathy and ventricular arrhythmias.
AB  - INTRODUCTION: Abnormal repolarization is one of the acknowledged mechanisms
      leading to malignant ventricular arrhythmias. We used a novel
      magnetocardiographic technique to investigate the role of inhomogeneous
      repolarization in patients with nonischemic dilated cardiomyopathy prone to
      sustained ventricular arrhythmias. METHODS AND RESULTS: Forty-nine dilated
      cardiomyopathy patients were studied, 18 with a history of sustained ventricular
      tachycardia (n = 6) or ventricular fibrillation (n = 12) and 31 with no
      ventricular arrhythmias. The magnetocardiogram was registered and QT apex and QT
      end intervals were determined by a computer algorithm. Inhomogeneity of
      repolarization was characterized with indices describing QT apex and QT end
      dispersion, and T wave end duration. In addition, time-domain late fields of the
      QRS complex in magnetocardiography and QT dispersion in 12-lead ECG were
      determined. T wave end was longer in the arrhythmia group in patients with sinus
      rhythm (87 +/- 15 msec vs 73 +/- 12 msec; P = 0.005) and in those not having
      bundle branch block. Magnetocardiographic late fields of the QRS complex were not
      different between groups. QT apex and end dispersion on magnetocardiography or 12
      lead ECG showed no difference. CONCLUSION: Prolongation of the end part of the T
      wave revealed by magnetocardiography is related to malignant ventricular
      arrhythmias in dilated cardiomyopathy. The results suggest that abnormal
      repolarization rather than delayed conduction underlies the arrhythmias in this
      disease.

PMID- 11469427
TI  - Magnetism: the last resort?

PMID- 11469428
TI  - Electrocardiographic analysis of ectopic atrial activity obscured by ventricular
      repolarization: P wave isolation using an automatic 62-lead QRST subtraction
      algorithm.
AB  - INTRODUCTION: Atrial activity on the surface ECG during premature beats and
      supraventricular arrhythmias frequently is obscured by the superimposed QRST
      complex of the previous cardiac cycle. This study examines the performance of a
      newly developed automatic QRST subtraction algorithm to isolate ectopic P waves
      from the preceding T-U wave. METHODS AND RESULTS: The 62-lead ECG recordings were
      obtained during (1) sinus rhythm and programmed right atrial stimulation in 12
      patients (group A); and (2) sinus rhythm and atrial premature beats, atrial
      tachycardia, or paroxysmal atrial fibrillation in 5 patients (group B). Pacing in
      group A patients was conducted at a slow drive cycle length to generate an
      ectopic P wave not obscured by the previous QRST complex and by delivering single
      premature extrastimuli at progressively shorter coupling intervals to produce an
      ectopic P wave obscured by the upsloping (early T-U wave), peak (middle T-U
      wave), and downsloping component of the T-U wave (late T-U wave). All ectopic P
      waves in group B patients were concealed by the preceding T-U wave. Automatic
      QRST subtraction was attained using an adaptive template constructed from
      averaged QRST complexes (mean 83 +/- 25 complexes) obtained during sinus rhythm
      (groups A and B) or atrial overdrive pacing (group A). P wave integral maps
      subsequently were computed, visually compared, and mathematically correlated. A
      high correspondence in spatial map pattern was observed between integral maps of
      "nonobscured" and previously "obscured" paced P waves obtained in group A
      patients (mean r = 0.88 +/- 0.07) as well as between integral maps of two to
      three previously obscured P waves with the same atrial arrhythmia morphology
      obtained in group B patients (mean r = 0.94 +/- 0.05). Improved morphologic P
      wave replication in group A patients was acquired when concealment occurred in
      the early (mean r = 0.90 +/- 0.08) or late part of the T-U wave (mean r = 0.90 +/
      0.06) as opposed to the middle T-U wave (mean r = 0.85 +/- 0.07) (P = NS and P <
      0.05 for early vs middle and late vs middle T-U wave, respectively). CONCLUSION:
      This novel automatic 62-lead QRST subtraction algorithm enables discrete
      isolation of T-U wave obscured ectopic atrial activity on the surface ECG while
      retaining the intricate spatial detail in P wave morphology. Future clinical
      application of the algorithm may enable improved ECG localization of focal
      triggers of paroxysmal atrial fibrillation, atrial tachycardia, and the atrial
      insertion of accessory pathways.

PMID- 11469429
TI  - Different mechanisms of isoproterenol-induced and nitroglycerin-induced syncope
      during head-up tilt in patients with unexplained syncope: important role of
      epinephrine in nitroglycerin-induced syncope.
AB  - INTRODUCTION: A reduction in left ventricular volume and an increase in
      epinephrine levels have been reported in tilt-induced neurally mediated syncope.
      To compare the mechanisms of isoproterenol-induced and nitroglycerin-induced
      syncope during head-up tilt and to investigate the role of catecholamines, the
      temporal changes in plasma levels of norepinephrine and epinephrine and in left
      ventricular volume were measured. METHODS AND RESULTS: The first study population
      consisted of 90 patients with syncope of unknown etiology and 12 control
      subjects. The second study population consisted of 43 patients with unexplained
      syncope. In the first study, head-up tilt (80 degree angle) was conducted for 40
      minutes, and norepinephrine and epinephrine levels were measured. In the second
      study, all patients were randomly allocated to either isoproterenol test (20
      patients) or nitroglycerin test (23 patients) for 20-minute head-up tilt.
      Isoproterenol infusion was given at a rate of 1 to 3 microg/min. Intravenous
      infusion of nitroglycerin was started at 250 microg/hour with increasing dosages
      up to 1,500 microg/hour. Norepinephrine and epinephrine were measured in
      peripheral venous blood. Left ventricular volumes were measured by
      echocardiography with patients in the supine position and during head-up tilt
      every 1 minute. End-diastolic volume and end-systolic volume were calculated. In
      the first study, 61 patients demonstrated a positive response and 29 patients
      demonstrated a negative response. Plasma norepinephrine changes during head-up
      tilt were not significantly different, whereas epinephrine levels were
      significantly higher in the positive patients than in the negative and control
      subjects (148 +/- 118 pg/mL vs 66 +/- 31 pg/mL and 55 +/- 27 pg/mL). Thirteen of
      the 20 patients given isoproterenol and 15 of the 23 patients given nitroglycerin
      showed a positive head-up tilt (65.0% vs 65.2%; P = NS). During isoproterenol and
      nitroglycerin infusion head-up tilt, epinephrine in the positive group determined
      by the nitroglycerin test was significantly higher than that in the other three
      groups (103 +/- 38 pg/mL vs 60 +/- 33 pg/mL, 31 +/- 21 pg/mL, and 50 +/- 52
      pg/mL). In contrast, end-systolic volume was significantly smaller in the
      positive group than in the other three groups based on findings of the
      isoproterenol test. CONCLUSION: The findings suggest that nitroglycerin triggers
      head-up tilt-induced syncope by increasing epinephrine levels, whereas
      isoproterenol induces syncope by decreasing left ventricular volume.

PMID- 11469430
TI  - Isoproterenol-provoked versus nitroglycerin-provoked tilt tests: do they differ?

PMID- 11469431
TI  - Sinus pacemaker function after cardioversion of chronic atrial fibrillation: is
      sinus node remodeling related with recurrence?
AB  - INTRODUCTION: The objective of this study was to investigate the temporal changes
      in sinus node function in postcardioversion chronic atrial fibrillation (AF)
      patients and their possible relation with the recurrence rates of AF. METHODS AND
      RESULTS: In 37 chronic AF patients, internally cardioverted to sinus rhythm,
      corrected sinus node recovery time (CSNRT), and the pattern of corrected return
      cycle lengths were assessed 5 to 20 minutes and 24 hours after conversion. The
      last 20 consecutive patients also were evaluated after autonomic blockade. Twenty
      subjects with normal atrial structure and no history of AF served as the control
      group. Patients were followed-up for 1 month for recurrence, and the density of
      supraventricular ectopic beats per hour was obtained during the first 24 hours
      after conversion. Fifteen patients (40.5%) relapsed during follow-up. CSNRT
      values at 600 msec (371 +/- 182 msec) and 500 ms (445 +/- 338 msec) were
      significantly higher than those of control subjects (278 +/- 157 msec, P = 0.050,
      and 279 +/- 130 msec, P = 0.037, respectively). Significant temporal changes in
      CSNRT also were observed during the first 24 hours after conversion (600 msec:
      308 +/- 120 msec, P = 0.034; 500 msec: 340 +/- 208 msec, P = 0.017). No
      significant interaction and temporal effects were observed with regard to
      corrected return cycle length pattern. Similar data regarding CSNRT and corrected
      return cycle length pattern were obtained after autonomic blockade. Patients with
      abnormal CSNRT after cardioversion had higher recurrence rates (50%) than those
      with normal function (37%; P = NS). Patients who relapsed had a higher density of
      supraventricular ectopic beats per hour (159 +/- 120) compared with those who did
      not (35 +/- 37; P = 0.001). CONCLUSION: Depressed sinus node function is observed
      after conversion of chronic AF. Recovery from this abnormality and its
      independence from autonomic function suggest that AF remodels the sinus node. Our
      data do not support a causative role of sinus node function in AF recurrence, but
      they do indicate such a role for the density of atrial ectopic beats.

PMID- 11469432
TI  - Sinoatrial remodeling caused by persistent atrial fibrillation: what is the
      relationship between postcardioversion sinus node dysfunction and increased
      atrial vulnerability?

PMID- 11469433
TI  - Pulmonary vein dilation in patients with atrial fibrillation: detection by
      magnetic resonance imaging.
AB  - INTRODUCTION: The positive relationship between left atrial (LA) size and atrial
      fibrillation (AF) is well recognized; however, there is little information on the
      association of pulmonary vein (PV) diameter and AF. The purpose of this study was
      to investigate by magnetic resonance angiography the change of PV and LA size in
      patients with no history of AF, patients with paroxysmal AF (PAF), and patients
      with chronic AF (CAF). METHODS AND RESULTS: The study included 47 patients. Group
      I included 15 patients with normal sinus rhythm and no history of documented AF.
      Group II included 24 patients with drug-refractory PAF who underwent
      electrophysiologic study and radiofrequency ablation of PV foci. Group III
      included 8 patients with CAF who were converted to sinus rhythm by external
      electrical cardioversion. Age and concomitant heart diseases were similar among
      the three groups. We measured the diameter of each PV at its junction with the LA
      in addition to LA dimensions by gadolinium-enhanced magnetic resonance
      angiography with three-dimensional reconstruction. Significant dilation of both
      superior PVs (P < 0.01) and transverse diameter of LA (P < 0.01) was seen in the
      three groups. There were no significant changes of both inferior PVs, corrected
      PV (PV/LA) diameter, or longitudinal diameter of LA among the three groups. Only
      28% patients showed arrhythmogenic foci from the largest PV. CONCLUSION:
      Significant dilation of both superior PVs with simultaneous LA enlargement was
      demonstrated i

PMID- 11469434
TI  - Echocardiographic lesion characteristics associated with successful ablation of
      inappropriate sinus tachycardia.
AB  - INTRODUCTION: Catheter ablation of inappropriate sinus tachycardia has proven
      difficult. Despite the use of intracardiac echocardiography to help direct
      radiofrequency (RF) application to the anatomic target of the superolateral
      crista terminalis (CT), multiple RF lesions often are required. Furthermore, the
      characteristic echo-anatomic changes with RF application associated with a
      reduction in heart rate have not been defined. A characteristic echo signature,
      if present, may facilitate the ablation process. The purpose of this
      retrospective study was to define the echocardiographic characteristic changes
      associated with effective RF ablation for inappropriate sinus tachycardia.
      METHODS AND RESULTS: Detailed intracardiac echocardiographic imaging
      characterization of the superolateral CT was performed before and at the time of
      successful heart rate reduction. Using on-line videotape intracardiac
      echocardiography (9 MHz, 9 French), changes in wall thickness and echodensity at
      the CT lesion site were assessed at baseline, after each RF lesion, and with the
      lesion that produced heart rate reduction in 17 patients (age 32 +/- 9 years; 15
      women) with inappropriate sinus tachycardia. In all patients, RF ablation was
      anatomically based and targeted only the superolateral CT. RF lesions were
      created using 20 to 50 W for up to 2 minutes using an 8-mm tip electrode.
      Successful heart rate reduction (> or = 20 beats/min) was achieved in 15 of 17
      patients and required 41 +/- 31 RF applications (range 5 to 110, median 40).
      Effective RF (reduced heart rate) was observed starting with the 34th +/- 24th
      lesion (range 3rd to 86th, median 25th). After effective RF, CT wall thickness
      was increased (11.4 +/- 3.1 mm vs 7.7 +/- 2.4 mm at baseline) and wall swelling
      expanded to adjacent superior vena cava, but the degree of thickening was not
      specific for effective RF associated with heart rate reduction. Importantly, we
      noted echodensity changes reaching directly to the epicardium with the
      development of a linear low echodensity or echo-free space at the time of
      effective RF resulting in heart rate reduction. In two patients without effective
      heart rate reduction, echodensity changes never reached the epicardium. No
      complications (superior vena cava-right atrial junction orifice narrowing >50% or
      pericardial effusion) of RF were identified. CONCLUSION: An echocardiographically
      guided anatomic approach to RF ablation of inappropriate sinus tachycardia is
      safe and effective. A characteristic echocardiographic signature suggesting
      transmural/epicardium damage appears to be present at the time of successful
      heart rate reduction and may serve as an appropriate guide for directing
      additional RF when using this anatomic echocardiographically based approach.

PMID- 11469435
TI  - New method for predicting efficiency of heating by measuring bioimpedance during
      radiofrequency catheter ablation in humans.
AB  - INTRODUCTION: Efficiency of heating (defined as the average temperature divided
      by the average power) during radiofrequency (RF) catheter ablation (RFCA) can be
      predicted by the electrode-tissue contact pressure before RFCA. To predict the
      efficiency of heating during RFCA, we prospectively measured bioimpedance and
      correlated the bioimpedance with the efficiency of heating in patients undergoing
      RFCA for supraventricular tachycardias. METHOD AND RESULTS: Of 239 RF
      applications in 55 patients, bioimpedance was measured from the distal pair of
      the electrodes of the ablation catheter using an extremely low current (10 microA
      at 45 kHz). Tip electrode temperature was measured with a closed-loop RF
      generator. Efficiency of heating and the difference (delta bioimpedance) between
      preablation bioimpedance (measured from the target ablation site) and baseline
      bioimpedance (measured in the right atrium without tissue contact) were
      calculated. There was significant positive correlation between preablation
      bioimpedance and efficiency of heating (regression coefficient = 0.053; P =
      0.003) and between delta bioimpedance and efficiency of heating (regression
      coefficient = 0.067; P = 0.003). The highest degree of correlation was found
      during RFCA of the accessory pathways in the left free wall (regression
      coefficient = 0.14; P < 0.01). With preablation delta bioimpedance >21.5 ohms,
      applications targeted at the left free-wall, left posteroseptal, or right septal
      accessory pathways had a greater likelihood of achieving effective tissue heating
      (defined as maximal temperature achieved >55 degrees C). CONCLUSION: Both
      preablation bioimpedance and delta bioimpedance have positive correlation with
      efficiency of heating during RFCA of supraventricular tachycardia. Measuring
      preablation bioimpedance appears to be a useful tool for predicting the
      efficiency of heating during RFCA.

PMID- 11469436
TI  - Shortening the second phase duration of biphasic shocks: effects of class III
      antiarrhythmic drugs on defibrillation efficacy in humans.
AB  - INTRODUCTION: The specific waveform providing optimal defibrillation threshold
      (DFT) is unknown. We compared the defibrillation efficacy of biphasic pulses with
      second phases (P2) of 2 and 5 msec in a randomized prospective clinical study.
      METHODS AND RESULTS: Intraoperative DFTs of 62 patients (age 54 +/- 13 years;
      ejection fraction 43% +/- 17%; amiodarone 47%, d,l-sotalol 13%) were determined
      in random order using a binary search protocol. Anodal shocks of 60% tilt first
      phases (P1) and P2 of 2 msec/5 msec were delivered from two 100-microF capacitors
      between the right ventricular electrode and the test housing of a Phylax 06/XM
      device. Mean DFT was significantly lower using the shorter P2 (9.5 +/- 4.5 J vs
      11.3 +/- 5.2 J; P < 0.0001). According to subgroup analysis, the effect of
      changing P2 duration was only influenced by antiarrhythmic treatment. DFT
      decreased markedly using the shorter P2 in patients treated with amiodarone (10.7
      +/- 4.9 J vs 13.4 +/- 5.6 J; P < 0.00001) or d,l-sotalol (6.1 +/- 3.3 J vs 9.1 +/
      4.6 J; P < 0.05). The difference in patients not treated with Class III drugs
      was found to be insignificant. Chronic amiodarone treatment increased DFT only
      when the longer P2 was used. CONCLUSION: Biphasic shocks with shorter P2 should
      be used in patients undergoing Class III antiarrhythmic treatment.

PMID- 11469437
TI  - Renaissance of waveform optimization? Class III antiarrhythmic drugs and the tail
      end of biphasic defibrillation shocks.

PMID- 11469438
TI  - Reduced anisotropy of action potential conduction in left ventricular
      hypertrophy.
AB  - INTRODUCTION: The aim of this study was to determine if anisotropic action
      potential conduction was altered during development of left ventricular
      hypertrophy (LVH). METHODS AND RESULTS: Isolated guinea pig left ventricular
      preparations from hearts that had developed LVH were used to measure conduction
      velocity in longitudinal and transverse orientations to the fiber direction. A
      variable degree of LVH was induced by placing a ring around the ascending aorta
      for 50 to 250 days. Results were compared with an age-matched control group that
      underwent a similar operation but with no ring placement. LVH was measured as the
      heart-to-body-weight ratio (HBR), which correlated with an increase of mean
      myocyte cross-sectional area. Longitudinal conduction velocity (LCV) declined
      progressively as HBR increased (mean +/- SD: sham vs LVH: HBR 3.74 +/- 0.30 g/kg
      vs 4.53 +/- 0.52 g/kg; LCV 72.8 +/- 15.5 vs 63.6 +/- 11.1 cm/sec). Mean
      transverse conduction velocity (TCV) was greater in LVH compared with control
      (20.5 +/- 4.7 cm/sec vs 25.4 +/- 8.1 cm/sec), but there was no significance in
      the trend as a function of HBR. The anisotropic ratio (LCV/TCV) significantly
      declined as HBR increased. The time constant of the foot of the action potential
      was smaller in the transverse compared with the longitudinal dimension. There was
      no influence of hypertrophy. CONCLUSION: The decrease of LCV and reduction of the
      anisotropic conduction ratio suggest remodeling of the tissue in LVH. The
      consequences for the generation of arrhythmias are discussed.

PMID- 11469439
TI  - Gap junctions and liminal length in hypertrophy: something old and something new.

PMID- 11469440
TI  - Spontaneous right ventricular outflow tract tachycardia in a patient with Brugada
      syndrome.
AB  - We report the case of a 28-year-old man with no structural heart disease, who
      exhibited clearly augmented ST segment elevation in the right precordial leads,
      followed by induction of spontaneous right ventricular outflow tract tachycardia
      with intravenous administration of Class IA antiarrhythmic drugs. The
      electrophysiologic mechanism of this tachycardia was thought to be triggered
      activity due to delayed afterdepolarizations. Due to the existence of substrates
      that were similar to Brugada syndrome combined with right ventricular outflow
      tract tachycardia, this case may represent a subtype of Brugada syndrome.

PMID- 11469441
TI  - On the neural connection.
AB  - Discoveries concerning cardiac neural-electrical modulation and local neural
      remodeling provide powerful new approaches for the development of novel
      antiarrhythmic strategies. This "view" of developments in this emerging field
      highlights recent advances and suggests that additional neurally targeted
      investigations have considerable potential for prevention of arrhythmic diseases.

PMID- 11469442
TI  - Twenty years of "hyperventilation": what is the arrhythmia mechanism?

PMID- 11469443
TI  - Accelerated junctional escape rhythm with retrograde P waves through alternating
      slow and fast pathways.

PMID- 11469444
TI  - Passive current redistribution in the heart.

PMID- 11469445
TI  - Proposed mechanism for the 2:1 conduction observed during arrhythmia.

PMID- 11469446
TI  - Classification of atrial flutter and regular atrial tachycardia according to
      electrophysiologic mechanism and anatomic bases: a statement from a joint expert
      group from the Working Group of Arrhythmias of the European Society of Cardiology
      and the North American Society of Pacing and Electrophysiology.
AB  - Regular atrial tachycardias classically are classified into flutter or
      tachycardia, depending on the rate and presence of a stable baseline on the ECG.
      However, current understanding of electrophysiology atrial tachycardias makes
      this classification obsolete, because it does not correlate with mechanisms. The
      proposed classification is based on electrophysiologic mechanisms, defined by
      mapping and entrainment. Radiofrequency ablation of a critical focus or isthmus
      can afford proof. Focal tachycardias are characterized by radial spread of
      activation and endocardial activation not covering the whole cycle. Ablation of
      the focus of origin interrupts the tachycardia. The mechanism of focal firing is
      difficult to ascertain by clinical methods. Macroreentrant tachycardias are
      characterized by circular patterns of activation that cover the whole cycle.
      Fusion can be shown during entrainment on the ECG or by multiple endocardial
      recordings. Ablation of a critical isthmus interrupts the tachycardia.
      Macroreentry can occur around normal structures (terminal crest, eustachian
      ridge) or around atrial lesions. The anatomic bases of these tachycardias must be
      defined, to guide appropriate treatment. Atrial flutter is a mere description of
      continuous undulation on the ECG, and only some strictly defined typical flutter
      patterns correlate with right atrial macroreentry bounded by the tricuspid valve,
      terminal crest, and caval vein orifices. This classification should be considered
      open, as some classically described tachycardias, such as reentrant sinus
      tachycardia, inappropriate sinus tachycardia, and type II atrial flutter, cannot
      be classified accurately. Furthermore, the possibility of fibrillatory conduction
      makes the limits with atrial fibrillation still ill defined.

PMID- 11469447
TI  - When is scleroderma really scleroderma?

PMID- 11469448
TI  - Arthroscopic synovectomy.

PMID- 11469449
TI  - MTX affects inflammation and tissue destruction differently in the rat AA model.
AB  - OBJECTIVE: To investigate the dose response relationships of methotrexate (MTX)
      therapy in rat adjuvant arthritis (AA), an animal model of rheumatoid arthritis
      (RA). METHODS: Female Lewis rats were fed a defined diet and were treated with 0,
      0.3, 1, 2, 3, 5, and 10 mg MTX per week beginning 3 days after adjuvant injection
      and lasting 6 weeks. The presence or absence of arthritis, and its degree were
      measured by hindpaw edema scores, ankle widths, and radiographic and
      histopathologic scores. RESULTS: The 2, 3, 5, and 10 mg MTX per week doses
      resulted in deaths before the end of the protocol and suppressed normal body
      weight gain. Tissue destruction, measured by radiographic and histopathologic
      scores, was reduced in a dose dependent manner with increasing MTX dose.
      Suppression of inflammation, measured by ankle widths and radiographic and
      histopathologic scores, reached a maximum at the 1 mg MTX dose and declined at
      higher doses. CONCLUSIONS: Suppression of tissue destruction and inflammation in
      rat AA does not occur in a concerted fashion as the dose of MTX increases. The
      implications of these findings to human disease remain to be determined.

PMID- 11469450
TI  - Splice variants VEGF121 and VEGF165 of the angiogenic peptide vascular
      endothelial cell growth factor are expressed in the synovial tissue of patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the expression of the angiogenic peptide vascular
      endothelial growth factor (VEGF, also known as vascular permeability factor, VPF)
      in the synovium of patients with rheumatoid arthritis (RA). METHODS: Expression
      of VEGF protein from the synovial tissue of 10 patients with RA was monitored by
      ELISA and visualized by immunocytochemistry, and by double-staining with the
      VEGFR-1/flt-1. VEGF mRNA and its splice variants were determined by reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: VEGF protein was
      strongly increased in rheumatoid synovium and localized at the synovial surface,
      whereas the VEGF receptor flt-1 (VEGFR-1) was visualized on microvessels in close
      vicinity. In synovial tissues from all 10 patients with RA, VEGF121 and VEGF165
      were identified at the mRNA level as the only VEGF splice forms expressed.
      CONCLUSION: Since VEGF165 and VEGF121 are differently diffusible due to their
      opposite heparan sulfate-binding properties, they act at different distances. The
      presence of VEGF121 may explain induction of the VEGFR-1 on infiltrating blood
      vessels near the synovial surface.

PMID- 11469451
TI  - Influence of HLA-DR alleles on rheumatoid arthritis: susceptibility and severity
      in Argentine patients.
AB  - OBJECTIVE: To determine the frequency of shared epitopes in our population of
      patients with rheumatoid arthritis (RA) and to investigate whether the presence
      of these alleles is associated with a more aggressive form of disease. METHODS:
      Demographic and clinical data were obtained from 140 patients with RA, 123
      female, mean age 49.9+/-11.7 years and mean disease duration 9.4+/-6.3 years.
      Radiographs of both hands were taken and scored by Larsen's method. HLA-DR
      alleles were determined by PCR-SSP. The control group comprised 202 healthy
      ethnic-matched subjects. RESULTS: DR4 was significantly more frequent in patients
      with RA than controls, and was observed in 70/140 patients (50%) versus 47/202
      controls (23.27%) (odds ratio 3.25, CI 1.99-5.35, Pcorr 5 x 10(-5)). Within DR4
      subtypes *0404 and *0401 were the most commonly found (37.7 and 29%,
      respectively). DR3 and DR11 exerted a protective effect with significantly higher
      frequency in controls than in patients with RA. When patients were divided into 2
      groups according to disease severity (radiographic score) the frequency of
      alleles with QKRAA and QRRAA sequences was similar in both groups. Although with
      lower frequency, subtype *1001 alone was significantly more frequent in the
      severe-condition group [7 (13.5%) vs 3 (3.4%), p = 0.03]. CONCLUSION: These
      results are in accordance with findings observed in Caucasians and differ from
      other Latin American populations. However shared epitope alleles failed to
      correlate with more severe disease with the exception of subtype *1001 which,
      although infrequent, was significantly more frequent in patients with relevant
      radiological damage.

PMID- 11469452
TI  - Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid
      arthritis.
AB  - OBJECTIVE: Osteopontin (OPN), secreted mainly from chondrocytes, is suggested to
      be involved in the ossification and remodeling of bone and also in regulation of
      cytokine profiles. We investigated whether patients with osteoarthritis (OA) and
      rheumatoid arthritis (RA) display autoimmunity against OPN. METHODS: Recombinant
      human OPN (rhOPN) was prepared as a fusion protein with beta-galactosidase using
      E. coli. Serum samples from patients with OA or RA and from age matched healthy
      donors were tested for autoantibodies to rhOPN using ELISA and Western blotting.
      Reactivity of the same samples to purified native human OPN (nhOPN) was
      investigated by ELISA separately, to evaluate conformational epitopes. RESULTS:
      By ELISA, autoantibodies to rhOPN were found in one (0.95%) of 105 patients with
      OA and 2 (2.3%) of 88 patients with RA. These autoantibodies to rhOPN were
      confirmed by Western blotting. In contrast, 11 (9.5%) of 105 OA serum and 13
      (15%) of 88 RA serum samples reacted to nhOPN. The anti-OPN positive RA patients
      showed high serum levels of rheumatoid factor and C-reactive protein and
      accelerated erythrocyte sedimentation rate compared to the anti-OPN negative
      group, although the differences did not achieve statistical significance.
      CONCLUSION: Our data showed that OPN is one of the autoantigens in OA and RA.
      Preferential recognition of nhOPN to rhOPN indicates that major epitope(s) of OPN
      would be conformational. Clinically, existence of the anti-OPN antibodies may be
      linked to disease severity in RA.

PMID- 11469453
TI  - Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis
      in patients with recently diagnosed rheumatoid arthritis.
AB  - OBJECTIVE: There is evidence that the hypothalamic pituitary adrenal (HPA) axis
      is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis
      responses to experimental stressors mimicking daily life challenges in patients
      with RA to determine whether HPA axis activity is associated with Th1 and Th2
      activity. METHODS: ACTH and cortisol responses in reaction to the succession of a
      bicycle ergometer task, a cold pressor task, and a computerized Stroop Color-Word
      interference test, as well as basal Th1 and Th2 cell activity, were assessed in
      29 patients (21 female, 8 male) with recently diagnosed RA (mean disease duration
      29 wks, range 5-69), mean age 55.7 years, none receiving glucocorticoid
      treatment, and 30 (20 female, 10 male) healthy age and sex matched controls (mean
      age 54.1 yrs). RESULTS: Mean ACTH and cortisol levels did not differ between the
      groups (p > 0.10). Patients tended to have a less pronounced ACTH response (F2.50
      = 2.7, p = 0.08) and had a significantly smaller cortisol response (P F2.50 =
      6.1, p < 0.01) than healthy controls in reaction to the stressors. This
      difference in cortisol response was reduced, but remained significant when ACTH
      responsiveness was accounted for by entering it as a covariate (P F2.49 = 3.7, p
      = 0.03). ACTH and cortisol levels and responses were not associated (all p >
      0.19) with basal interferon-gamma and interleukin 4 as reflections of Th1 and Th2
      cell activity, respectively. HPA axis activity was not linked to current disease
      activity. CONCLUSION: Our findings show reduced HPA axis responsiveness in RA
      patients with recent diagnosis receiving longterm medication that is suggested to
      be located both at a hypothalamic/pituitary and at an adrenal level. It appears
      that common HPA axis activity accomplishes low amounts of cortisol release, which
      makes it difficult to determine an influence of endogenous cortisol changes on
      the Th1/Th2 balance.

PMID- 11469454
TI  - Adaptation and validation of the rheumatoid arthritis quality of life scale for
      use in Canada.
AB  - OBJECTIVE: The Rheumatoid Arthritis Quality of Life questionnaire (RAQoL) was
      developed simultaneously in the UK and the Netherlands to measure quality of life
      in patients with RA. We adapted and validated the RAQoL for the English-Canadian
      and French-Canadian languages and culture. METHODS: The UK RAQoL was translated
      into French-Canadian by a bilingual translation panel. Separate lay panels were
      then used to ensure that this and the English-Canadian instruments were
      appropriate for use with Canadian patients. Interviews were conducted with 15
      French-Canadian and 15 English-Canadian patients with RA to determine the content
      validity. Reliability and construct validity were established by means of test
      retest mail surveys conducted with 92 French-Canadian and 87 English-Canadian RA
      patients. The survey consisted of the adapted RAQoL, the Health Assessment
      Questionnaire (HAQ), and a demographic questionnaire. RESULTS: The RAQoL was
      successfully adapted for both the French and English-Canadian cultures. Field
      testing showed both versions to be well received by respondents. Of the French
      Canadian patients included in the postal survey, 52 responded at Time 1 and 50 at
      Time 2. For the English-Canadian sample, 54 responded at both time points.
      Missing data rates for the RAQoL were low and floor and ceiling effects were
      minimal. Test-retest reliability was good for both versions: 0.87 for the French
      Canadian and 0.95 for the English-Canadian. Alpha coefficients (0.92 for the
      French-Canadian, 0.93 for the English-Canadian) showed the items to be adequately
      interrelated and scores on the measure showed moderate to high correlations with
      the HAQ, confirming construct validity. Both versions of the RAQoL were also able
      to distinguish patient groups that differed according to perceived health status
      and perceived severity of RA. In addition, the French-Canadian version was able
      to distinguish patients who rated today as bad or very bad from those who rated
      today as good or very good. CONCLUSION: The new versions of the RAQoL were well
      received by both French and English speaking Canadians. The psychometric quality
      of the adapted questionnaires means they are suitable for inclusion in clinical
      trials involving patients with RA.

PMID- 11469455
TI  - Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive
      study.
AB  - OBJECTIVE: To study the presence of chronic coexisting diseases in patients with
      rheumatoid arthritis (RA) and its effect on RA treatment, disease course, and
      outcome during the first years of the disease. METHODS: From January 1985 to
      December 1990, 186 patients with recent onset RA were enrolled in a prospective
      longitudinal study. Between January 1991 and November 1992 patients were
      interviewed on the basis of a comorbidity questionnaire. For analysis the
      diseases were coded according to the International Classification of Diseases,
      9th revision, Clinical Modification (ICD-9-CM) medical diagnoses. Disease
      activity during the period of followup was measured by the Disease Activity
      Score. Outcome in terms of physical disability (Health Assessment Questionnaire)
      and radiological damage (Sharp's modified version) over 3 and 6 year periods was
      determined. RESULTS: In the group of 186 patients, with mean disease duration of
      4.3 years at January 1991, 50 patients (27%) reported at least one chronic
      coexisting disease. The most frequently reported coexisting diseases were of
      cardiovascular (29%), respiratory (18%), or dermatological (11%) origin. For the
      major part (66%) chronic coexisting diseases were already present before onset of
      RA. No statistically significant differences in use of disease modifying
      antirheumatic drugs or corticosteroids were observed between RA patients with and
      without chronic coexisting diseases. No statistically significant differences
      were found in disease activity or in outcome in terms of physical disability and
      radiological damage over 3 and 6 year periods between the 2 groups with RA.
      CONCLUSION: The results showed that about 27% of patients with RA in this
      inception cohort had at least one chronic coexisting disease. Treatment, disease
      course, and outcome did not differ between patients with and without chronic
      coexisting diseases during the first years of the disease.

PMID- 11469456
TI  - Arthroscopic synovectomy for rheumatoid arthritis using a holmium:YAG laser.
AB  - OBJECTIVE: To determine the usefulness of the holmium:YAG laser system in
      arthroscopic synovectomy (ASSX) for treating rheumatoid arthritis (RA). METHODS:
      ASSX was performed on 15 knees (one Larsen Grade 1, 7 Grade 2, 7 Grade 3) and 8
      ankles (6 Grade 2, 2 Grade 3) of 17 female patients with RA. The average age at
      ASSX was 50.6 years (25-70). The average followup period was 24.4 months (10-47).
      RESULTS: Seven out of 8 knees with grade 1 or 2 had reduced pain and swelling, as
      well as decreased average serum levels of C-reactive protein (CRP) (from 3.6+/
      1.1 to 1.4+/-0.3 mg/dl). However, 4 out of 7 knees with grade 3 showed recurrence
      of pain and swelling along with persistent average serum level of CRP (from 4.3+/
      1.0 to 3.8+/-1.0 mg/dl). All 8 ankles with Grade 2 or Grade 3 experienced reduced
      pain and swelling, while the average serum CRP levels did not change (from 3.2+/
      0.9 to 2.9+/-1.0 mg/dl). CONCLUSION: The Holmium:YAG laser was useful in ASSX for
      treating RA knees and ankles.

PMID- 11469457
TI  - Serologic evaluations of women exposed to breast implants.
AB  - OBJECTIVE: There continues to be uncertainty whether women with silicone breast
      implants experience activation of their immune system and show increased
      prevalence of serologic markers of connective tissue diseases. We conducted
      laboratory tests in a large number of women with and without breast implants, and
      in diabetic patients with presumed silicone exposure via insulin syringes.
      METHODS: Subjects were chosen from women enrolled in the run-in phase of the
      Women's Health Study (WHS, a randomized trial testing aspirin and vitamin E in
      preventing cardiovascular disease and cancer), and included 298 women without
      breast implants, 298 women with breast implants, and 52 diabetic patients
      diagnosed before age 30. Comparison groups were matched on age, race, date of
      blood provided to the WHS, and randomization status. We compared the proportion
      with abnormal results in 16 serologic tests among the 3 groups of women,
      stratifying by the matching factors. We also tested for monoclonal
      immunoglobulins by electrophoresis. RESULTS: For 14 of the 16 serologic tests,
      the proportions with abnormal results among the 3 groups of women were not
      significantly different. Of the remaining tests, C3 levels were decreased in 8
      (2.7%) women without breast implants and 22 (7.4%) women with breast implants (p
      = 0.003). C4 levels were decreased in 31 (10.4%) women without breast implants
      and 48 (16.1%) women with breast implants (p = 0.03). Women without breast
      implants and diabetic patients did not differ significantly in the proportions
      having decreased C3 and C4 levels. Women with breast implants did not have higher
      frequency of monoclonal immunoglobulins detected by electrophoresis. CONCLUSION:
      We found little evidence for activation of the immune system in women with breast
      implants. The clinical significance of isolated reductions in C3 and C4 levels,
      in the absence of other abnormalities such as elevated levels of antinuclear
      antibody, is unknown.

PMID- 11469458
TI  - Characterization of changes in IgG associated oligosaccharide profiles in
      rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis using
      fluorophore linked carbohydrate electrophoresis.
AB  - OBJECTIVE: To investigate fluorophore linked carbohydrate electrophoresis (FCE)
      as a method of analyzing serum immunoglobulin G (IgG) oligosaccharides in healthy
      individuals and those with rheumatic disease and compare with lectin binding
      assays of carbohydrate composition. METHODS: IgG was isolated from patients with
      rheumatoid arthritis (RA) (n = 21), ankylosing spondylitis (AS) (n = 20),
      psoriatic arthritis (PsA) (n = 20), and healthy adults (n = 36). IgG
      oligosaccharides were released enzymatically, fluorescently labelled using 8
      aminonaphthalene-136 trisulfonic acid; and identification of the oligosaccharide
      bands was by stepwise enzymatic degradation. Comparison of FCE was made with
      lectin binding analysis in which the lectins Ricinus communis (RCA1) and
      Bandeiraea simplicifolia (BSII) were used to detect galactose (Gal) and N
      acetylglucosamine (GlcNAc), respectively. RESULTS: Each disease could be
      differentiated from healthy adults on the basis of Band 1 asialodigalacto core
      fucosylated oligosaccharide (gf2) intensity (p = 0.001), but not from each other.
      Reduced levels of different sugars were associated with specific diseases:
      reduced gf2 with RA (p < 0.001), PsA (p < 0.001) and AS (p < 0.02), reduced Band
      5 disialo-digalacto core fucosylated (a2f) oligosaccharide with AS (p < 0.001),
      reduced Band 6 disialo-digalacto (a2) oligosaccharide with AS (p < 0.001) and PsA
      (p = 0.021). All diseases were associated with a significant increase in Band 4
      asialo-agalacto core fucosylated oligosaccharide (g0f) (p < 0.001). In RA, FCE
      band intensities correlated with sugar quantity when identified using lectin
      binding analysis (p < 0.003). In contrast, there was no correlation between the
      same bands in healthy individuals. CONCLUSION: FCE is an accurate method of
      analyzing IgG associated oligosaccharides and reveals unique band patterns or
      sugar prints associated with healthy adults and patients with RA, PsA, and AS,
      and comparison with lectin binding analysis suggests undetected RA glycoprotein
      structural differences. FCE has potential in the early diagnosis and
      differentiation of rheumatic diseases.

PMID- 11469459
TI  - Excess autoimmune disease mortality among school teachers.
AB  - OBJECTIVE: To investigate evidence of an association between school teaching and
      mortality from autoimmune diseases. METHODS: A proportional mortality study using
      US death certificates from the 1985-95 period was conducted. Death certificates
      that listed elementary or secondary school teaching as the usual occupation were
      identified, as were those that cited any of 13 autoimmune diseases as a cause of
      death. Proportional mortality ratios (PMR) were calculated to compare autoimmune
      disease mortality among teachers to that among persons in other professional
      occupations. RESULTS: The PMR for total autoimmune disease mortality among
      teachers was 113 (p < 0.0001). Rheumatic diseases accounted for 53.1% of the
      total excess in mortality and multiple sclerosis accounted for 39.9%.
      Significantly elevated autoimmune disease mortality occurred for female teachers
      (PMR = 111, p < 0.0001), male teachers (PMR = 124, p < 0.0001), white teachers
      (PMR = 112, p < 0.0001), non-white teachers (PMR = 118, p = 0.005), elementary
      teachers (PMR = 111, p < 0.0001), and secondary teachers (PMR = 130, p < 0.0001).
      There was an inverse trend (p < 0.0001) in the level of excess mortality relative
      to age. PMR were 149, 144, 127, 118, 108, and 102 for teachers in the 35-44, 45
      54, 55-64, 65-74, 75-84, and > or = 85 year age groups, respectively. Excess
      mortality was significantly greater in secondary teachers than elementary
      teachers both in total (PMR = 112, p = 0.04) and in the 35-44 age group (PMR =
      155, p = 0.03). CONCLUSION: Our results substantiate excess mortality from
      autoimmune diseases among teachers and suggest that, relatively early in their
      careers, teachers experience an occupational exposure that increases risk of
      autoimmune diseases.

PMID- 11469460
TI  - Antiprolactin autoantibodies in systemic lupus erythematosus: frequency and
      correlation with prolactinemia and disease activity.
AB  - OBJECTIVE: To determine in patients with systemic lupus erythematosus (SLE) (1)
      the frequency of antiprolactin (anti-PRL) autoantibodies, and (2) the
      relationships among anti-PRL autoantibodies, serum prolactin (PRL) levels, and
      lupus activity. METHODS: In a cross sectional study 259 consecutive patients with
      SLE were tested for serum PRL levels and anti-PRL autoantibodies based on disease
      activity. RESULTS: The frequency of anti-PRL was 5% (13/259), and all SLE
      patients with anti-PRL had hyperprolactinemia. There was lupus activity in 110
      patients (42.5%) and there was no significant difference in frequency of anti-PRL
      autoantibodies between patients with or without lupus activity (5.5 vs 4.7%; p =
      0.99). Only a high level of serum PRL was associated with lupus activity
      independent from other studied variables (p = 0.024). There was a negative but
      nonsignificant correlation between the titers of anti-PRL autoantibody and SLEDAI
      (r(s) = -0.16, p = 0.59). Anti-PRL positive patients had higher levels of serum
      PRL than anti-PRL negative patients (33.2+/-13.8 vs 11.6+/-13.2 ng/ml; p =
      0.0001) and a significantly different frequency of hyperprolactinemia (100 vs
      11.4%; p = 0.00001). CONCLUSION: The presence of anti-PRL autoantibodies was
      associated with hyperprolactinemic status and high serum PRL levels; these data
      suggest that anti-PRL autoantibodies could be the cause of hyperprolactinemia in
      a subset of patients with SLE. An increase in serum PRL levels proved to be an
      important independent factor related to lupus activity, but there was no
      relationship between anti-PRL autoantibodies and lupus activity.

PMID- 11469461
TI  - HLA markers and clinical characteristics in Caucasians with primary Sjogren's
      syndrome.
AB  - OBJECTIVE: To explore the association between HLA genotypes and clinical and
      immunological characteristics in Caucasians with primary Sjogren's syndrome
      (pSS). METHODS: HLA genotyping for DRB1, DQA1 and DQB1 was carried out in 62
      single case patients with pSS and 64 healthy controls. The specific amino acid
      residues at DQA1 position 34 (DQalpha-34Q) and DQB1 position 26 (DQbeta-26L) in
      addition to the DQ-DI (AA59-AA69) motif were deterrmined. Subsequently, the
      relative contribution of individual HLA markers to clinical and immunologic
      characteristics of pSS was assessed by group comparisons. RESULTS: No significant
      associations were seen between HLA markers and histopathological or clinical
      features of pSS. Significant positive associations with HLA Class II markers were
      restricted to the formation of different autoantibodies. Formation of an anti
      Ro/SSA and anti-La/SSB autoantibody response was positively associated with
      DRB1*03, DQB1*02 and DRB1*03/DRB1*15-DQB1*02/DQB1*0602 heterozygosity. Patients
      positive for anti-La/SSB also showed a strong positive anti-La/SSB association
      with DQA1*0501. Considering the contribution of individual DQA1 and DQB1 amino
      acids and sequence motifs to the formation of anti-Ro/SSA and anti-La/SSB
      autoantibodies, a dose dependent positive influence was detected for DQalpha-34Q
      and DQbeta-26L. For DQbeta-DI, the largest difference between patients and
      controls was seen for the presence of a single copy of this motif after selecting
      patients with either anti-Ro/SSA or anti-La/SSB autoantibodies. CONCLUSION: The
      association of HLA Class II markers with pSS may concern the anti-Ro/La response
      rather than the disease itself. The strongest contributors to the formation of an
      anti-Ro/La response included components of the DRB1*03-DQB1*02-DQA1*0501
      haplotype also encompassing the transethnically-associated DQbeta-DI motif. In
      addition, the dose dependent contribution of DQalpha-34Q and DQbeta-26L argue for
      a recessive contribution of HLA-DQ to the formation of an anti-Ro/La response.
      Given the prominent associations with DRB1*03 and the complex dose dependent
      interactions at HLA-DQ, a joint contribution of HLA-DR and DQ is likely to be
      relevant for the formation of anti-Ro/La autoantibodies in patients with pSS.

PMID- 11469462
TI  - Left ventricular diastolic function in systemic sclerosis.
AB  - OBJECTIVE: To assess left ventricular diastolic function in patients with
      systemic sclerosis (SSc) and to verify if a "primary" diastolic dysfunction might
      exist. METHODS: In total 124 patients and 41 healthy subjects underwent complete
      echocardiographic examination. The following pulsed wave Doppler variables were
      evaluated: peak velocity during early filling (E), peak velocity during late
      atrial filling (A), E/A ratio, and early filling deceleration time. RESULTS:
      Seventy-seven patients (62.1%) had conditions potentially affecting left
      ventricular diastolic function (Group A) and 47 patients (37.9%) formed a
      homogeneous group without cardiac involvement or other causes of abnormal
      diastolic function (i.e., systemic and/or pulmonary hypertension, ventricular
      hypertrophy, pericardial disease, systolic dysfunction, valvular heart disease,
      coronary artery disease) (Group B). The entire SSc population and Group A showed
      significant differences in the Doppler variables of diastolic function compared
      to the control group. No significant differences were found between Group B and
      controls. CONCLUSION: In patients with SSc, left ventricular diastolic
      dysfunction was found only in patients with conditions potentially affecting left
      ventricular diastolic function. In patients without conditions potentially
      affecting left ventricular diastolic function no differences were seen in
      comparison with controls. SSc does not seem to cause "primary" diastolic
      abnormalities.

PMID- 11469463
TI  - Cyclooxygenase-2 expression and prostaglandin E2 biosynthesis are enhanced in
      scleroderma fibroblasts and inhibited by UVA irradiation.
AB  - OBJECTIVE: We and others reported on the beneficial effects of combined therapy
      using 8-methoxypsoralen and long wave ultraviolet light (PUVA therapy) in the
      treatment of scleroderma. We now investigate the mechanism by which PUVA therapy
      is effective by comparing interleukin 1beta (IL-1beta) mediated signal
      transduction in scleroderma fibroblasts and those from normal skin. METHODS:
      Prostaglandin E2 (PGE2) production and expression of cytosolic phospholipase A2
      (cPLA2), cyclooxygenase (COX)-1, and COX-2 (enzymes that regulate PGE2
      production) were examined in untreated and IL-1beta treated fibroblasts from
      scleroderma involved and normal skin. The effect of UVA irradiation on enzyme
      expression and PGE2 production was examined. PGE2 was measured by a competitive
      radioimmunoassay and enzyme expression was analyzed by Western immunoblotting and
      Northern blotting. RESULTS: Constitutive PGE2 production was significantly
      upregulated and IL-1beta induced PGE2 production was increased by the enhancing
      expression of both COX-2 mRNA and protein in fibroblasts from scleroderma
      involved skin; PGE2 production and COX-2 expression were inhibited by UVA
      irradiation. CONCLUSION: Enhanced PGE2 production regulated by COX-2 expression
      in scleroderma fibroblasts may contribute to the development of this disorder.
      PUVA therapy might exhibit its beneficial effect, at least in part, by inhibiting
      COX-2 expression transcriptionally and translationally, with subsequent
      inhibition of PGE2 production.

PMID- 11469464
TI  - Criteria for the classification of early systemic sclerosis.
AB  - We propose criteria for the early diagnosis and classification of systemic
      sclerosis that reflect the vascular and serological advances of the last 2
      decades.

PMID- 11469465
TI  - Association of HLA class II genes with systemic sclerosis in Koreans.
AB  - OBJECTIVE: To investigate HLA class II associations with systemic sclerosis (SSc)
      in Koreans according to anti-topoisomerase I (anti-topo I), anti-centromere
      antibody (ACA), and anti-U1 ribonucleoprotein (RNP) status. METHODS: HLA class II
      alleles (DRB1, DRB5, DQB1) were determined by DNA typing in 200 healthy control
      subjects and 74 patients with SSc: 35 anti-topo I positive, 3 ACA positive, and
      19 anti-U1 RNP positive; among them were 34 diffuse and 40 limited subtypes, and
      16 overlap syndrome. RESULTS: Anti-topo I positive SSc was strongly associated
      with DRB1*1502 compared with both controls (23% vs 5%; Pcorr = 0.003) and anti
      topo I negative patients (23% vs 3%; p = 0.009); our study confirms observations
      in Japanese. HLA-DR 67FLEDR71, especially 38V-67FLEDR71 sequence (carried on
      DRB5*0102 in linkage disequilibrium with DRB1*1502, DRB1*0802, DRBI*1101), showed
      the strongest association with anti-topo I response (46% vs 16% in controls;
      Pcorr = 0.001), and 38L-67FLEDR71 group alleles were not associated with anti
      topo I response. Anti-topo I response was not significantly associated with HLA
      DQB1 alleles in Koreans. There were only 3 ACA positive patients, and all
      patients had DRB1*1501 and DQB1*0602 as heterozygotes. Anti-U1 RNP occurred at a
      high frequency (63%) among patients with overlap syndrome, and was not associated
      with HLA-DR or DQ genes. Among anti-topo I negative patients, diffuse and limited
      subtypes of SSc were significantly associated with DRB1*0803 (47% vs 15% in
      controls; Pcorr < 0.05) and DRB1*1501 (50% vs 17% in controls; Pcorr < 0.01),
      respectively. These HLA associations have not been reported in other ethnic
      groups and possible associations with certain autoantibody subsets remain to be
      confirmed. CONCLUSION: HLA-DR gene has a primary association with anti-topo I
      response, and HLA-DR 38V-67FLEDR71 group alleles including DRB5*0102 (in linkage
      disequilibrium with DRB1*1502) show the strongest association with anti-topo I
      response in Korean patients with SSc.

PMID- 11469466
TI  - Diagnostic performance of antineutrophil cytoplasmic antibody tests for
      idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase
      antibodies.
AB  - OBJECTIVE: The diagnostic value of tests for antimyeloperoxidase antibodies (anti
      MPO) for systemic vasculitis is less established than that for cytoplasmic
      antineutrophil cytoplasmic antibody (cANCA)/antiproteinase 3 antibodies (anti
      PR3). Controversy exists regarding the optimal utilization of indirect
      immunofluorescence (IIF) ANCA testing versus antigen-specific ANCA testing. To
      summarize the pertinent data, we conducted a metaanalysis examining the
      diagnostic value of ANCA testing systems that include assays for anti-MPO.
      METHODS: We performed a structured Medline search and reference list review.
      Target articles in the search strategy were those reporting the diagnostic value
      of immunoassays for anti-MPO for the spectrum of systemic necrotizing
      vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis,
      the Churg-Strauss syndrome, and isolated pauci-immune necrotizing or crescentic
      glomerulonephritis, regardless of other types of ANCA tests. Inclusion criteria
      required specification of a consecutive or random patient selection method and
      the use of acceptable criteria for the diagnosis of vasculitis exclusive of ANCA
      test results. Weighted pooled summary estimates of sensitivity and specificity
      were calculated for anti-MPO alone, anti-MPO + perinuclear ANCA (pANCA), and anti
      MPO/pANCA + anti-PR3/cANCA. RESULTS: Of 457 articles reviewed, only 7 met the
      selection criteria. Summary estimates of sensitivity and specificity (against
      disease controls only) of assays for anti-MPO for the diagnosis of systemic
      necrotizing vasculitides were 37.1% (confidence interval 26.6% to 47.6%) and
      96.3% (CI 94.1% to 98.5%), respectively. When the pANCA pattern by IIF was
      combined with anti-MPO testing, the specificity improved to 99.4%, with a lower
      sensitivity, 31.5%. The combined ANCA testing system (anti-PR3/cANCA + anti
      MPO/pANCA) increased the sensitivity to 85.5% with a specificity of 98.6%.
      CONCLUSION: These results suggest that while anti-MPO is relatively specific for
      the diagnosis of systemic vasculitis, the combination system of immunoassays for
      anti-MPO and IIF for pANCA is highly specific and both tests should be used
      together given the high diagnostic precision required for these conditions.
      Because patients with ANCA associated vasculitis have either anti-MPO with pANCA
      or anti-PR3 with cANCA, and rarely both, a combined ANCA testing system including
      anti-PR3/cANCA and anti-MPO/pANCA is recommended to optimize the diagnostic
      performance of ANCA testing.

PMID- 11469467
TI  - Percutaneous conchotome muscle biopsy. A useful diagnostic and assessment tool.
AB  - OBJECTIVE: To evaluate the diagnostic yield, performance simplicity, and safety
      of the percutaneous conchotome muscle biopsy technique for clinical and research
      purposes in an outpatient rheumatology clinic. METHODS: Biopsies taken by
      rheumatologists in an outpatient clinic during 1996 and 1997 were evaluated for
      histopathological and clinical diagnoses. RESULTS: A total of 149 biopsies were
      performed on 122 patients. Physicians learned the method easily. Samples were of
      adequate size and quality to allow for diagnostics. In total 106 biopsies were
      taken due to different diagnostic suspicions: 24 polymyositis (PM) or
      dermatomyositis (DM); 43 PM, DM, or vasculitis in addition to another rheumatic
      condition; 19 systemic vasculitis; and 20 myalgias. Criteria for definite or
      probable PM/DM were fulfilled in 21 patients, 18 with positive biopsies. Thirteen
      patients received vasculitis as clinical diagnosis, 3 with positive biopsies. No
      patient with myalgia had a biopsy with inflammatory changes. Fifteen of 43
      rebiopsies performed to assess disease activity had signs of active inflammation.
      In 48% there were changes in immunosuppressive therapy after biopsy results. Four
      complications occurred; one was a serious subfascial hematoma. CONCLUSION: The
      percutaneous conchotome muscle biopsy technique gives a good size sample that
      allows for diagnostic evaluation and has a high yield in patients with myositis.
      It is a simple procedure, easy to learn and to perform, with a low complication
      rate and minimum discomfort for the patient. The method can preferably be used as
      a diagnostic tool and to perform repeated biopsies to assess the effect of a
      given therapy for both clinical and research purposes.

PMID- 11469468
TI  - Lack of association between intercellular adhesion molecule-1 gene polymorphisms
      and giant cell arteritis.
AB  - OBJECTIVE: Studies have shown an association between HLA-DRB1*04 and giant cell
      arteritis (GCA). Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms
      were reported to contribute susceptibility to GCA in Italian patients where
      susceptibility to GCA is not associated with HLA-DRB1*04 alleles. ICAM-1 is also
      highly expressed within inflammatory infiltrates of the blood vessels of GCA
      patients. To investigate the clinical implications of ICAM-1 polymorphisms in
      GCA, we examined their potential association and influence in the development of
      visual ischemic complications in a series of patients with GCA from Northwest
      Spain where GCA susceptibility is associated with HLA-DRB1*04. METHODS: Fifty
      eight biopsy proven GCA and 129 ethnically matched controls were studied.
      Patients and controls were genotyped for ICAM-1 polymorphism at codons 241 and
      469 by PCR-RFLP. RESULTS: The distribution of the alleles and genotypes for each
      ICAM- polymorphism did not show significant differences between GCA patients and
      controls. Although visual manifestations were significantly more likely to occur
      in men than women (OR 5.2, p = 0.018), allele and genotype frequencies of ICAM-1
      polymorphisms in patients with GCA were not associated with development of visual
      complications or anemia. Visual complications in GCA were primarily associated
      with carriage of an HLA-DRB1*04 allele. No evidence was found for interaction
      between HLA-DRB1*04 and ICAM-1 polymorphism. CONCLUSION: ICAM-1 polymorphisms are
      not genetic risk factors for the susceptibility and severity of GCA in Northwest
      Spain.

PMID- 11469469
TI  - Clinical and imaging correlates of response to treatment with infliximab in
      patients with ankylosing spondylitis.
AB  - OBJECTIVES: Ankylosing spondylitis (AS) is a chronic disease leading to
      progressive spinal ankylosis and deformity. The aims of this study were to (1)
      determine whether infliximab is an effective treatment for AS patients who have
      failed conventional treatment; (2) identify any baseline clinical variables that
      can be associated with responsiveness to treatment; and (3) resolve whether the
      clinical response correlated with changes from baseline inflammatory changes on
      magnetic resonance imaging (MRI). METHODS: Twenty-one patients who met the
      modified New York criteria for AS (M:F 18:3) were enrolled in this open labeled
      study. The mean age was 37.9+/-7.9 years and mean disease duration was 8.69+/
      6.58 years. Patients received infliximab at a dose of 5 mg/kg by intravenous
      infusion over 2 hours at 0, 2, 6, weeks. Nine functional variables were measured
      [i.e., Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI)
      etc.], 6 clinimetrics (chest expansion, finger to floor, etc.), and inflammatory
      markers in the peripheral blood at baseline and each subsequent visit. Primary
      response to treatment was defined as a > 20% response in 5/9 functional
      variables. A subset of 9 consecutive patients was selected for MRI scans before
      and after infusions. RESULTS: Eighteen patients were available for assessment at
      week 14 having received 3 infusions (wks 0, 2, 6). There was > 60% improvement in
      functional variables, i.e., BASDAI, BASFI, Health Assessment Questionnaire,
      fatigue, and spinal and total body pain. Clinimetric scores selectively improved,
      e.g., chest expansion (p < 0.021) by 14 weeks. ESR, CRP and haptoglobin all
      showed significant improvement at 6 weeks and were maintained to the 14 week
      assessment point. Imaging studies showed improvement in all patients studied
      including those with advanced disease. Three patients developed headache during
      the infusions. Infliximab was effective in all, but degree of response varied.
      Very good responders were distinguished from good responders by shorter duration
      of disease and better baseline clinimetric scores. CONCLUSIONS: Infliximab was an
      effective treatment for AS in a short term trial. Longterm control of symptoms
      and potential alteration in clinical course of disease will require longterm
      assessment.

PMID- 11469470
TI  - Cathepsin K in aseptic hip prosthesis loosening: expression in osteoclasts
      without polyethylene wear particles.
AB  - OBJECTIVE: To investigate the expression of the bone matrix degrading cysteine
      proteinase cathepsin K and to determine the colocalization of cathepsin K with
      polyethylene (PE) particles in tissue specimens of patients with aseptic hip
      prosthesis loosening (AHPL). METHODS: The expression of cathepsin K was studied
      by immunohistochemistry in tissue specimens of 9 patients with aseptically
      loosened acetabular components of failed cementless total hip replacements. The
      expression of cathepsin K was compared to that of the macrophage marker CD68 by
      serial section analysis. Double labeling of the expression of cathepsin K or CD68
      by immunohistochemistry and of PE particles by modified Oil Red staining method
      was performed. RESULTS: Cathepsin K could be predominantly detected in
      osteoclasts attached to the bone tissue, while only a few (CD68+) mononuclear and
      multinucleated foreign body giant cells (MGC) were positive for this enzyme. By
      double labeling with Oil Red staining we found the majority of CD68 positive
      cells of the periprosthetic tissue that were colocalized with PE particles.
      However, cathepsin K-expressing osteoclasts could not be stained with Oil Red.
      CONCLUSION: The present data suggest that in AHPL neither mononuclear cells nor
      MGC but rather osteoclasts are mainly involved in cathepsin K mediated bone
      matrix destruction. Using double labeling of immunohistochemistry and Oil Red
      staining we observed that the cathepsin K-expressing osteoclasts did not include
      PE particles.

PMID- 11469471
TI  - Pigmented villonodular synovitis. Review of 20 cases.
AB  - OBJECTIVE: Pigmented villonodular synovitis (PVS) is a rare aggressive lesion.
      Inclusion of this disease in the differential diagnosis of rheumatoid arthritis
      can lead to early diagnosis and treatment. In this retrospective study we
      evaluated diagnostic procedures, therapies, and outcomes of PVS. METHODS: Twenty
      surgically treated cases of PVS were evaluated: joint, 16; tenosynovial, 3; and
      bursa, one. The 20 patients had undergone the following surgeries: 4 total
      synovectomies, 2 subtotal synovectomies, eight arthroscopically assisted
      resections, 4 resections of extraarticular lesions, and 2 arthroplasties. The
      mean followup was 17.5 mo (1-54). RESULTS: At diagnosis, pain was present in 19
      of 20 cases. Joint swelling or a tumor was found in 11 cases, and 12 patients
      complained of repeated joint effusions. The mean duration of symptoms was 23.8 mo
      (range 1-144). Half the cases had a nodular pattern and the other half a diffuse
      pattern. The most common location of PVS was the knee (14 patients). Surgical
      treatment before admission did not always lead to an accurate diagnosis. For
      example, in 2 patients, arthroscopy did not reveal PVS. In 2 patients a soft
      tissue sarcoma was suggested. In 3 patients, the diagnosis was made incidentally
      with arthroscopy or arthroplasty. On radiographs, bone lesions were seen in 8
      cases; in 13 of 17 cases the diagnosis was by magnetic resonance imaging (MRI).
      After surgery 17 patients stayed free of recurrence, 14 without symptoms. One
      patient who had an incidental diagnosis of PVS has a synovectomy planned as a
      second procedure. One patient awaits a second dorsal procedure after a ventral
      knee synovectomy. One patient shows recurrent disease 33 mo after resection of a
      nodular knee lesion. CONCLUSION: PVS should be included in the differential
      diagnosis of any arthritis. MRI is the most effective diagnostic tool in
      identifying PVS. The treatment of PVS consists of surgical excision in sound
      tissue. A total synovectomy should be the treatment of choice in diffuse disease.
      From the literature, nonsurgical therapies, such as steroid injections, 90Y
      synoviorthesis, or external beam radiation, seem to be of benefit in selected
      patients.

PMID- 11469472
TI  - Transforming growth factor-beta induced collagenase-3 production in human
      osteoarthritic chondrocytes is triggered by Smad proteins: cooperation between
      activator protein-1 and PEA-3 binding sites.
AB  - OBJECTIVE: To examine the signaling pathways leading to transforming growth
      factor-beta (TGF-beta) induced collagenase-3 production in human osteoarthritic
      (OA) chondrocytes, as well as the transcription factors and their binding sites
      involved in the transcriptional control of collagenase-3 gene. METHODS:
      Identification of the TGF-beta signaling pathway was by Western immunoblotting
      using specific antibodies for the phosphorylated forms of p44/42 and p38 MAPK,
      SAPK/JNK, and the Smad2 protein. Electromobility shift assays (EMSA) were carried
      out for activator protein- (AP-1), polyomavirus enhancer A (PEA-3), activin
      response-element-like, Smad-binding-element-like, and TGF-beta inhibitory element
      oligonucleotides. Supershift assays using antibodies to the Jun, Fos, and Smad
      families of proteins were used for identification of transcription factors.
      Chondrocyte transfections were also performed using the -133CAT collagenase-3
      promoter plasmid (containing PEA-3, AP-1, and TATA sites) and mutated AP-1 and
      PEA-3 sites. RESULTS: The primary target of TGF-beta induced collagenase-3 in OA
      chondrocytes was the Smad2 protein, with significant phosphorylation within 5
      min. Contrasting with the Smad2, the untreated OA chondrocytes already had
      detectable levels of the phosphorylated forms of p38 and p44/42 MAPK. Of the
      oligonucleotides tested, EMSA revealed that TGF-beta treated OA chondrocyte
      proteins bound only to the AP-1 and PEA-3. Supershifts with the AP-1
      oligonucleotide showed the presence of the Jun (c-Jun, JunB, JunD) and Fos (c
      Fos, FosB, Fra-1, Fra-2) proteins in the untreated and TGF-beta treated OA
      chondrocytes, whereas only Smad proteins (Smad2, 3, 4) were present in the AP-1
      binding proteins from the TGF-beta treated chondrocytes. The AP-1 mutation
      decreased both basal (95%) and TGF-beta induced (99%) collagenase-3 production,
      whereas the PEA-3 mutation decreased the basal (15%) but more significantly (50%)
      the TGF-beta induced transcription. CONCLUSION: Smad proteins are the main
      cytoplasmic signaling pathways in TGF-beta stimulated collagenase-3 in OA
      chondrocytes. The AP-1 site appears critical for upregulation of collagenase-3
      production, but TGF-beta stimulation requires both AP-1 and PEA-3 sites for
      optimal response.

PMID- 11469473
TI  - Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey
      in Taiwan (1993-96).
AB  - OBJECTIVE: To evaluate the prevalence of hyperuricemia in Taiwan. METHODS: A
      multi-stage stratified sampling scheme was used in Nutrition and Health Survey,
      which was conducted in Taiwan between 1993 and 96. Complete biochemical and
      questionnaire data for 2754 males and 2953 females aged 4 years and older were
      included in the analysis. The colorimetric enzymatic method was used to measure
      plasma uric acid in fasting blood samples. Information on self-reported,
      physician-diagnosed gout was also obtained. RESULTS: The uric acid values of
      males were found to reach a peak between the ages of 13 and 18 and decrease
      slightly after 18. The uric acid values of females were stable before the age of
      18, decreasing slightly between 19 and 44 years, and increasing in the mid to
      older age groups (> or = 45 years). Twenty-six percent of adult males (> or = 19
      years) and 22% of older males (> or = 45 years) either had hyperuricemia (serum
      uric acid > 458.0 microM or 7.7 mg/dl) or were taking medication for it.
      Seventeen percent of adult females and 23% of older females either had
      hyperuricemia (serum uric acid > 392.57 microM or 6.6 mg/dl) or were taking
      medication for it. Both adult males and females in mountainous areas, who were
      primarily aboriginal, had the highest prevalence of hyperuricemia (> 50%) among
      the 7 survey areas. Mean body mass index (BMI), alcohol consumption, and
      prevalence of gout were among the highest in mountainous people compared to all
      included in the study. Multivariate analysis showed that mountainous area, age
      and BMI are important factors associated with hyperuricemia in males, whereas
      mountainous area, Class II townships, and BMI are the factors associated with
      hyperuricemia in females. CONCLUSIONS: We found a high prevalence of
      hyperuricemia in Han Chinese in Taiwan despite a lack both of obesity and high
      alcohol consumption. Mountainous people (mainly aborigines) in Taiwan have an
      even higher prevalence of hyperuricemia, which cannot be completely explained by
      obesity and alcohol consumption. Genetic components and other environmental
      factors may have contributed to this pattern of hyperuricemia.

PMID- 11469474
TI  - Estimating the costs of job related arthritis.
AB  - OBJECTIVE: To present the first estimate of the costs of job related
      osteoarthritis (OA) in the USA. METHODS: Data were drawn from national data sets
      collected by the US Bureau of Labor Statistics, the US National Center for Health
      Statistics, and existing cost estimates for arthritis in the literature. We used
      proportional attributable risk (PAR) models to estimate the percentage of acute
      and repetitive injuries resulting in OA. These PAR vary between men and women. We
      used the human capital method that decomposes costs into direct categories such
      as medical expense and indirect categories such as lost earnings. RESULTS: We
      estimate job related OA costs US$3.41 to 13.23 billion per year (1994 dollars).
      Our point estimate is that job related OA contributes about 9% ($8.3 billion) to
      the total costs for all OA. About 51% of job related costs result from medical
      costs and 49% from lost productivity at work and at home. These costs are likely
      to underestimate the true burden since costs of pain and suffering as well as
      costs to family members and others who provide home care are ignored. CONCLUSION:
      The cost of job related arthritis is significant and has implications for both
      clinical and public policy. Depending on the PAR selected, job related arthritis
      is at least as costly as job related renal and neurological disease combined, and
      is on a par with the costs of job related chronic obstructive pulmonary disease
      and all asthma, whether job related or not.

PMID- 11469475
TI  - The efficacy of home based progressive strength training in older adults with
      knee osteoarthritis: a randomized controlled trial.
AB  - OBJECTIVE: To test the effects of a high intensity home-based progressive
      strength training program on the clinical signs and symptoms of osteoarthritis
      (OA) of the knee. METHODS: Forty-six community dwelling patients, aged 55 years
      or older with knee pain and radiographic evidence of knee OA, were randomized to
      a 4 month home based progressive strength training program or a nutrition
      education program (attention control). Thirty-eight patients completed the trial
      with an adherence of 84% to the intervention and 65% to the attention control.
      The primary outcome was the Western Ontario and McMaster Universities
      Osteoarthritis (WOMAC) index pain and physical function subscales. Secondary
      outcomes included clinical knee examination, muscle strength, physical
      performance measures, and questionnaires to measure quality of life variables.
      RESULTS: Patients in the strength training group who completed the trial had a
      71% improvement in knee extension strength in the leg reported as most painful
      versus a 3% improvement in the control group (p < 0.01). In a modified intent to
      treat analysis, self-reported pain improved by 36% and physical function by 38%
      in the strength training group versus 11 and 21%, respectively, in the control
      group (p = 0.01 for between group comparison). In addition, those patients in the
      strength training group who completed the trial had a 43% mean reduction in pain
      (p = 0.01 vs controls), a 44% mean improvement in self-reported physical function
      (p < 0.01 vs controls), and improvements in physical performance, quality of
      life, and self-efficacy when compared to the control group. CONCLUSION: High
      intensity, home based strength training can produce substantial improvements in
      strength, pain, physical function and quality of life in patients with knee OA.

PMID- 11469476
TI  - Growth hormone, insulin, and insulin-like growth factor-1 in hypermobility
      syndrome.
AB  - OBJECTIVE: To investigate growth factors in patients with hypermobility syndrome
      (HMS), namely insulin, insulin-like growth factor-1 (IGF-1), and growth hormone
      (GH). METHODS: Standard radioimmunoassay quantified serum levels of insulin, IGF
      1, and GH in 24 women and 7 men with HMS, and in suitable age and sex matched
      controls. Several patients with other heritable connective disorders were also
      studied, including congenital hip dysplasia and severe kyphosis. RESULTS:
      Patients with HMS and with otherwise unexplained joint and muscle pain were found
      to have elevated levels of insulin, IGF-1, and GH. Patients with heritable
      connective tissue disorders had elevated GH levels, and several patients had
      elevated insulin and IGF-1 levels. CONCLUSION: In patients with HMS, elevation of
      serum growth factors helps establish the diagnosis. GH alone can induce muscle
      and joint pain.

PMID- 11469477
TI  - Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis.
AB  - OBJECTIVE: To evaluate the in vitro production of interleukin 6 (IL-6) by
      peripheral blood mononuclear cells (PBMC) of patients with systemic juvenile
      idiopathic arthritis (JIA), its regulation by IL-10, and the association of
      abnormal regulation of IL-6 production with presence of polymorphisms in the
      regulatory sequence of the IL-6 gene. METHODS: PBMC were cultured in the absence
      or presence of lipopolysaccharide (LPS). IL-6 and IL-10 levels were measured by
      ELISA. Polymorphisms in the regulatory sequences of the IL-6 gene were assessed
      by restriction fragment length polymorphism analysis and sequencing of amplified
      regions. RESULTS: Patients' PBMC produced high amounts of IL-6 compared to
      controls in unstimulated conditions. The IL-10 50% inhibitory dose of LPS
      stimulated IL-6 production was significantly higher in patients than controls. IL
      10 levels produced in the absence or presence of LPS were comparable between
      patients and controls. The -174 G/C polymorphism in the IL-6 gene does not appear
      to be correlated with the high unstimulated IL-6 production or with the reduced
      inhibition by IL-10 observed in patients with JIA. No differences in patients
      compared to controls and with respect to the published sequence were found in the
      3' untranslated region (UTR) of the IL-6 gene. CONCLUSION: Most patients with JIA
      have increased unstimulated production of IL-6 and reduced inhibition of IL-6
      production by IL-10. This abnormal regulation of IL-6 production is not secondary
      to a defect in IL-10 production, and is not associated with polymorphism of
      alleles at position -174 of the 5' flanking region or with mutations in the 3'
      untranslated region of the IL-6 gene.

PMID- 11469478
TI  - Safety and efficacy of high dose etanercept in treatment of juvenile rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate safety and efficacy of high dose etanercept (> 0.8 mg/kg,
      maximum 25 mg subcutaneously twice weekly) (Enbrel) in children with juvenile
      rheumatoid arthritis (JRA) and inadequate prior response to standard dose
      etanercept. METHODS: Retrospective chart review of 8 children (6 girls, 2 boys,
      mean age 8.4 yrs, range 5-16 yrs). Five children had systemic onset,
      polyarticular course JRA; 2 had polyarticular onset; and one had pauciarticular
      onset, polyarticular course JRA. All children had failed at least 3 mo (mean 9
      mo) treatment with standard dose etanercept (0.4 mg/kg SC twice a week). All 8
      children had increase in the etanercept dose to at least 0.8 mg/kg (mean 1.1
      mg/kg, maximum 25 mg SC twice weekly) for a mean of 7 mo (range 3-10 mo).
      Efficacy of high dose etanercept was evaluated by changes in joint count,
      laboratory data, and ability to decrease concomitant medication. RESULTS:
      Improvements in the joint count and laboratory findings (erythrocyte
      sedimentation rate, hemoglobin and platelet count) were observed in 2 of 8 (25%)
      children. In these 2, concomitant prednisone was reduced or discontinued. In
      contrast, no changes in disease activity or laboratory findings were observed in
      the other 6 children. Overall, high dose etanercept was well tolerated. No
      laboratory abnormalities were detected and no child withdrew because of adverse
      events. CONCLUSION: High dose etanercept is safe and well tolerated in children,
      but efficacy seems limited. In children with unsatisfactory response to standard
      dose etanercept, an increased dose or treatment prolongation may not offer any
      additional benefit.

PMID- 11469479
TI  - Acute rheumatic fever and poststreptococcal reactive arthritis: diagnostic and
      treatment practices of pediatric subspecialists in Canada.
AB  - OBJECTIVE: We conducted a survey of pediatric specialists in rheumatology,
      cardiology, and infectious diseases to ascertain present Canadian clinical
      practice with respect to diagnosis and treatment of acute rheumatic fever (ARF)
      and poststreptococcal reactive arthritis (PSReA), and to determine what variables
      influence the decision for or against prophylaxis in these cases. METHODS: A
      questionnaire comprising 6 clinical case scenarios of acute arthritis occurring
      after recent streptococcal pharyngitis was sent to members of the Canadian
      Pediatric Rheumatology Association, and to heads of divisions of pediatric
      cardiology and pediatric infectious diseases at the 16 university affiliated
      centers across Canada. RESULTS: There is considerable variability with respect to
      diagnosis in cases of ReA following group A streptococcal (GAS) infection both
      within and across specialties. There is extensive variability regarding the
      decision to provide prophylaxis in cases designated as ARF or PSReA. Findings
      indicated that physicians are most comfortable prescribing antibiotic prophylaxis
      in the presence of clear cardiac risk and are less inclined to such intervention
      for patients diagnosed with PSReA. When prophylaxis was recommended for cases of
      PSReA, the majority of respondents prescribed longer term courses of antibiotics.
      CONCLUSION: The lack of observed consistency in diagnosis and treatment in cases
      of reactive arthritis post-GAS infection likely reflects the lack of universally
      accepted criteria for diagnosis of PSReA and insufficient longterm data regarding
      carditis risk within this population. There is a need for clear definitions and
      treatment guidelines to allow greater consistency in clinical practice across
      pediatric specialties.

PMID- 11469480
TI  - Isolated temporomandibular synovitis as unique presentation of juvenile
      idiopathic arthritis.
AB  - Temporomandibular joint (TMJ) involvement is quite frequent in juvenile
      idiopathic arthritis (JIA). We describe a 15-year-old girl with isolated TMJ
      arthritis presenting as a unique manifestation of JIA, and its successful
      treatment. She underwent arthroscopic synovectomy followed by intraarticular
      steroid injection. Early use of synovectomy and intraarticular steroids in TMJ
      arthritis may reduce pain, improve jaw function, and prevent irreversible
      deformities.

PMID- 11469481
TI  - Successful treatment of retroperitoneal fibrosis with tamoxifen in a child.
AB  - We describe our experience with tamoxifen in a prepubertal girl with
      retroperitoneal fibrosis who had failed treatment with high dose corticosteroid
      therapy. Her response was excellent.

PMID- 11469482
TI  - Remitting seronegative symmetrical synovitis with pitting edema associated with
      subcutaneous Streptobacillus moniliformis abscess.
AB  - We describe an 84-year-old woman who developed remitting seronegative symmetrical
      synovitis with pitting edema (RS3PE) associated with a subcutaneous abscess of
      the hand due to Streptobacillus moniliformis. Polyarthritis and edema were
      relieved after therapy with corticosteroids. We review the association of RS3PE
      to different rheumatologic, neoplastic, or infectious diseases.

PMID- 11469483
TI  - Remitting seronegative symmetrical synovitis with pitting edema following
      intravesical bacillus Calmette-Guerin instillation.
AB  - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare
      syndrome of undetermined etiology occurring in the elderly. We describe the first
      case of RS3PE in a HLA-B27 positive 65-year-old man following intravesical
      bacillus Calmette-Guerin (BCG) instillation for bladder carcinoma. He developed
      symmetrical arthritis and synovitis involving wrists, knees, ankles, and
      metatarsophalangeal joints, with marked pitting edema of the dorsa of both hands
      and feet, fever, and elevated acute phase reactants. Right knee effusion revealed
      nonspecific sterile inflammatory fluid. He responded dramatically to nonsteroidal
      antiinflammatory drugs. BCG instillation may have triggered active symmetrical
      synovitis via local T cell activation and a T-helper-1 (Th-1)/Th-2 inflammatory
      profile.

PMID- 11469484
TI  - Male osteoporosis associated with longterm cyproterone treatment.
AB  - A 58-year-old man with previous dorsal vertebral fractures was referred for
      continuing management of osteoporosis. He was treated in the past with
      cyproterone acetate for hypersexuality. There were no other risk factors for
      osteoporosis. A dual energy radiographic absorptiometry scan confirmed
      osteoporosis. Treatment with alendronate 10 mg/day improved bone density and back
      pain. Patients receiving longterm treatment with cyproterone might be at risk for
      developing osteoporosis and would benefit from regular bone density monitoring.

PMID- 11469485
TI  - Starting a disease modifying antirheumatic drug or a biologic agent in rheumatoid
      arthritis: standards of practice for RA treatment.
AB  - Our aim was to investigate the practices and standards by which disease modifying
      antirheumatic drugs (DMARD) and biologics are and have been prescribed. We
      reviewed the literature and examined data from patients with rheumatoid arthritis
      (RA) participating in a national cohort: the National Data Bank for Rheumatic
      Diseases (NDB). Four pathways for DMARD prescription were identified: (1) A time
      based pyramidal approach (the RA pyramid); (2) a severity-based pyramid in which
      the most effective treatment is given to those with more active disease; (3) a
      cost-based pathway in which the primary goal is cost containment--this pathway
      intertwines with the severity-based pathway; and (4) a patient preference pathway
      where treatment is geared to patient needs and wishes regardless of severity.
      Data show that the time-based and severity-based pathways are not generally used
      in contemporary expert practice, and that patients with all degrees of severity
      and disease duration are receiving DMARD and biologic treatment. With the
      abandonment of the pyramid and the development of effective therapy, rheumatic
      disease care has swung away from the imperative of time and severity-based
      treatment to the imperative of care based on patient preference. It is the
      standard of practice to treat patients with mild and early disease with
      aggressive therapy, with the goal of limiting subsequent damage and retarding
      progression, and with the realistic purpose of relieving symptoms. The standard
      may at times be in conflict with the goals of insurers, but there is no
      legitimate medical reason for such limitations.

PMID- 11469486
TI  - Evaluation and documentation of rheumatoid arthritis disease status in the
      clinic: which variables best predict change in therapy.
AB  - To determine in clinical practice which rheumatoid arthritis (RA) clinical status
      variables are most associated with a change in disease modifying antirheumatic
      drug (DMARD) therapy, we studied 26,240 observations from 1905 RA patients
      occurring over 25 years. Variables included tender joint count, erythrocyte
      sedimentation rate (ESR), grip strength, visual analog scale for pain, global
      severity, fatigue and sleep, Health Assessment Question functional disability
      scale (HAQ), anxiety, depression and morning stiffness. Only the tender joint
      count required a physician. Observations at which a change in DMARD therapy
      occurred were compared to those where a change did not occur using generalized
      estimating equations (GEE) and classification and regression tree analysis
      (CART). Tender joint count, pain, global severity, and ESR were the 4 variables
      most strongly predictive of DMARD change. CART modeling indicated a special role
      for fatigue and sleep disturbance in some patients. These data add support in
      clinical practice for the ACR core set and the DAS set of variables. In addition,
      they validate the use of these variables in a practice setting. We suggest a
      minimum set of evaluations comprising: joint count, ESR or CRP, measures of pain
      and/or severity, a fatigue scale (fatigue being a surrogate for sleep
      disturbance), and a measure of function such as the HAQ or modified HAQ. Because
      only joint count requires physician participation, these evaluations are
      practical for the clinic, and allow quantitative measurement of RA status. With
      the use of quantile charts, the comparative status of RA and the change in RA
      status can be determined easily.

PMID- 11469487
TI  - Markers for work disability in rheumatoid arthritis.
AB  - Work disability is common in rheumatoid arthritis (RA), and accounts for a large
      fraction of its costs. People with RA who are work disabled have more joint
      involvement, radiographic damage, and/or laboratory abnormalities than people who
      are working. However, analysis of predictive and associative markers in 15
      studies of work disability indicate that the demographic variables, such as age,
      occupation, level of education, and duration of disease, as well as functional
      status in activities of daily living (ADL) identified on a patient questionnaire,
      appear to identify work status more than physiological variables. Work disability
      results from complex interactions of a medical disease, demographic variables,
      social conditions, and government policies. Some patients with RA are work
      disabled before they see a rheumatologist. Improved work disability outcomes in
      RA will require attention to social, economic, and political issues, and wider
      physician and public education concerning RA, in addition to improved medical
      management of disease.

PMID- 11469488
TI  - Quantitative target values of predictors of mortality in rheumatoid arthritis as
      possible goals for therapeutic interventions: an alternative approach to
      remission or ACR20 responses?
AB  - Predictors of longterm mortality in rheumatoid arthritis (RA) include patient
      questionnaire measures, grip strength, walk time, physician and patient
      assessment of global status, joint examination abnormalities, erythrocyte
      sedimentation rate (ESR), and morning stiffness. In the rheumatology literature,
      these measures have been analyzed primarily according to mean values in groups or
      regression analyses, which are valuable to recognize that mortality in RA is
      predicted by more severe disease, but do not provide the clinician with specific
      goals of therapy. Goals for therapeutic intervention are often expressed either
      as complete remission or as statistically significant differences versus a
      placebo, as in a 20% or even 50% response of a measure such as the American
      College of Rheumatology Core Data Set. Remission may be too stringent, while
      statistically significant efficacy of a drug compared to placebo may not
      necessarily indicate effectiveness to control longterm damage. An alternative
      approach might be to identify possible target values for therapeutic efficacy
      that markers of a poor prognosis be "near normal" rather than necessarily at
      normal or remission levels, as has been explored in management of hypertension
      and diabetes. However, it remains uncertain whether the goal of therapy should be
      a "near normal" or entirely normal values for a clinical marker. Better control
      of quantitative markers that predict early mortality could provide a valuable
      approach to improving outcomes in RA.

PMID- 11469489
TI  - Women in rheumatology.

PMID- 11469490
TI  - Do antifilaggrin antibodies within the "normal" range predict rheumatoid
      arthritis?

PMID- 11469491
TI  - Temporal arteritis associated with Chlamydia pneumoniae DNA detected in an artery
      specimen.

PMID- 11469492
TI  - Incidence of elbow involvement in rheumatoid arthritis.

PMID- 11469493
TI  - The use of botulinum toxin-A in the treatment of patients with fibromyalgia.

PMID- 11469494
TI  - Tolosa-Hunt syndrome mimicking giant cell arteritis.

PMID- 11469495
TI  - Effect of antimalarial agents on fasting lipid profile in systemic lupus
      erythematosus.

PMID- 11469496
TI  - Tumor cell adhesion under hydrodynamic conditions of fluid flow.
AB  - Current evidence indicates that tumor cell adhesion to the microvasculature in
      host organs during formation of distant metastases is a complex process involving
      various types of cell adhesion molecules. Recent results have shown that
      stabilization of tumor cell adhesion to the microvascular vessel wall is a very
      important step for successful tumor cell migration and colonization of host
      organs. We are beginning to understand the influences of fluid flow and local
      shear forces on these adhesive interactions and cellular responses within the
      circulation. Mechanosensory molecules or molecular complexes can transform shear
      forces acting on circulating tumor cells into intracellular signals and modulate
      cell signaling pathways, gene expression and other cellular functions. Flowing
      tumor cells can interact with microvascular endothelial cells mediated mainly by
      selectins, but the strength of these bonds is relatively low and not sufficient
      for stable cell adhesions. Integrin-mediated tumor cell adhesion and changes in
      the binding affinity of these adhesion molecules appear to be required for
      stabilized tumor cell adhesion and subsequent cell migration into the host organ.
      Failure of the conformational affinity switch in integrins results in breaking of
      these bonds and recirculation or mechanical damage of the tumor cells. Various
      cell signaling molecules, such as focal adhesion kinase, pp60src or paxillin, and
      cytoskeletal components, such as actin or microtubules, appear to be required for
      tumor cell adhesion and its stabilization under hydrodynamic conditions of fluid
      flow.

PMID- 11469497
TI  - From malformations to molecular mechanisms in the male: three decades of research
      on endocrine disrupters.
AB  - For three decades, we have known that estrogens alter the development of the
      mammalian reproductive system in predictable ways. In mice exposed prenatally to
      diethylstilbestrol (DES) or other estrogens, the male offspring exhibit
      structural malformations including cryptorchidism, epididymal cysts and retained
      Mullerian ducts. The estrogen-associated alterations in the genital tract
      phenotype can be usefully considered as a model called Developmental
      Estrogenization Syndrome. While estrogen treatment during critical periods of
      morphogenesis of the male reproductive system has been associated with these
      changes, the mechanisms at the molecular level are still being discovered.
      Parallel findings on the hormones involved in Mullerian duct regression and
      testicular descent have helped guide research on the mechanisms of developmental
      estrogenization of the male. Cellular localization of molecular signals
      associated with key steps in genital tract development, use of mice with gene
      disruption, and knowledge of the mechanisms underlying persistent changes in gene
      expression are beginning to provide a blue print for both the physiological role
      and pathological effects of estrogens in reproductive tract development. Since
      many of the same biological principles underlie genital tract morphogenesis in
      mammals, one may expect some of the same changes in males of other species
      exposed to estrogen during the appropriate developmental periods.

PMID- 11469498
TI  - Residues from anabolic preparations after good veterinary practice.
AB  - The purpose of this study was to determine the endogenous concentrations of
      estrogens, particularly estradiol-17beta (E2beta, in edible tissues of beef
      cattle (females and intact and neutered males) and the concentrations of E2beta,
      and trenbolone beta and alpha (betaTb, alphaTb) after an E2beta and/or trenbolone
      acetate (TA) ear implant. Radioimmunoassays were validated for quantitation of
      E2beta (active isomer), E2alpha, estrone (E1), betaTb and alphaTb for bovine
      muscle, liver, kidney and fat tissues. The criteria of accuracy, precision,
      specificity and sensitivity were applied according to the standards of the U.S.
      Food & Drug Administration. In steer tissues, endogenous E2beta was <15 ppt, as
      was heifer muscle; but heifer liver and kidney were 3-fold greater. An E2beta
      implant in steers had no effect on muscle E2beta concentration, but increased
      E2beta in liver and fat 4- and 3-fold, respectively, but by 24 h post-implant
      removal, E2beta had fallen by half. Tissue E1 concentrations in cyclic females
      were similar to E2beta, but rose many fold greater than did E2beta during
      gestation; E2beta rose 3-fold during gestation. After E2beta/TA implant, steer
      tissues had E2beta concentrations equal to (for muscle and fat) and one-half (for
      liver) the E2beta measured in E2beta implant only steers; betaTb was in a low
      range (250-380 ppt) in muscle, liver and fat and alphaTb was even lower, except
      in liver (800-1500 ppt). An implant of TA only (no E2beta) resulted in betaTb and
      alphaTb concentrations 2-3-fold greater in liver, kidney and fat, but no greater
      in muscle than betaTb in tissues of E2beta/TA implant steers. In conclusion,
      anabolic implants in steers resulted in tissue E2beta concentrations less than
      the FDA allowable increment and betaTb in the lowest quartile (0.25) of a part
      per billion 30 days after implant.

PMID- 11469499
TI  - Rapid immunodiagnosis of streptococci and enterococci in blood cultures.
AB  - We evaluated a procedure for rapid identification of blood culture isolates of
      pneumococci, enterococci and beta-haemolytic streptococci groups A, B, C, and G.
      Immunological tests were applied directly to blood culture medium and included a
      quellung reaction for pneumococci, and latex agglutination tests (LAT) for
      pneumococcal antigen and Lancefield antigens A, B, C, D and G. During a one-year
      trial period with approximately 12,000 blood culture sets (BacT/Alert, Organon
      Teknika), 208 sets showed pure growth of gram-positive cocci in pairs or chains
      by direct microscopy. Overall, a correct diagnosis was noted for 103 (63.2%, 95%
      CI: 55.3-70.6%) of 163 sets yielding pneumococci, beta-haemolytic streptococci,
      or enterococci. A procedure excluding Lancefield antigens only A, B, and D was
      implemented during a one-year follow-up period. With this simplified procedure
      positive and negative predictive values, respectively, were 1.00 and 0.87 for
      pneumococci, 1.00 and 0.94 for beta-haemolytic streptococci group A, 0.60 and
      1.00 for beta-haemolytic streptococci group B, and 0.91 and 0.88 for enterococci.
      We conclude that rapid identification of gram-positive cocci is feasible and may
      improve the information given to clinicians at the first notification of positive
      blood cultures.

PMID- 11469500
TI  - Comparison of endobronchial and transbronchial biopsies with high-resolution CT
      (HRCIT) in the diagnosis of sarcoidosis.
AB  - High-resolution computed tomography (HRCT) has been shown to accurately visualise
      parenchymal infiltrates of sarcoidosis. The aim of this study was to compare the
      diagnostic yield (DY) of HRCT with that of endobronchial (EBB) and transbronchial
      (TBB) biopsies in establishing the diagnosis of sarcoidosis. Forty-five patients
      referred to Helsinki University Central Hospital with a presumptive diagnosis of
      sarcoidosis underwent fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage
      (BAL), EBB, TBB and HRCT. Thirty-seven of the patients were diagnosed as having
      sarcoidosis, 34 of whom showed a parenchymal infiltrate in HRCT. One of the three
      patients with no parenchymal findings, had positive findings in TBB, and all had
      lymphocytosis in BAL. The DY for sarcoidosis by EBB and TBB was 24.3% and 50.0%,
      respectively. The addition of EBB to TBB improved the DY by 8.3%, whereas adding
      TBB to EBB improved the DY by 30.6%. There were no major complications after the
      FOB, which was always performed under fluoroscopic control. In conclusion, HRCT
      is a valuable tool in diagnosing sarcoidosis. However, the HRCT findings cannot
      be seen in all patients with positive findings in lung biopsy, nor is the
      parenchymal infiltrate specific for sarcoidosis. Attempting biopsy-proven
      diagnosis of sarcoidosis is still recommended. Fiberoptic bronchoscopy with EBB
      and TBB under fluoroscopic control is a safe and well-tolerated procedure.

PMID- 11469501
TI  - Absence of group II phospholipase A2, a Paneth cell marker, from the epididymis.
AB  - Paneth cell-like metaplasia has been reported in the epithelium of the epididymis
      and prostatic adenocarcinomas. We studied the expression of group II
      phospholipase A2 (PLA2), a marker of Paneth cell differentiation, in six
      orchiectomy specimens with Paneth cell-like metaplasia. Both immunohistochemistry
      for group II PLA2 protein and in situ hybridization for the mRNA of group II PLA2
      gave negative results in all six cases but positive reaction for lysozyme. The
      results show that the cells of the Paneth cell-like metaplasia are not true
      Paneth cells.

PMID- 11469502
TI  - A test for cleaning and disinfection processes in a washer-disinfector.
AB  - Disinfection processes such as heat, aldehydes or alcohols kill vegetative
      microorganisms but do not necessarily remove other organic contamination. Organic
      residues impair the result of low-temperature sterilisation processes. Heat
      stable organic residues may give rise to clinical symptoms in the patient.
      Standards are available in Britain and in Sweden for the examination of cleaning
      processes in washer-disinfectors. The test substances are artificial soil or
      blood. These standards are based on visual inspection of instruments or
      equipment. They cannot be used for examination of tubular instruments, nor can
      they be quantified. For validation of cleaning procedures a simple quantifiable
      method, which can be performed in an infection control laboratory is needed. We
      have used suspensions in horse blood of Enterococcus faecalis bacteria and
      Bacillus subtilis spores to test disinfection and cleaning in a washer
      disinfector. Instruments used for laparoscopic surgery were contaminated with a
      blood bacteria suspension containing 10(7) organisms/ml and then dried and
      processed in a washer-disinfector using a regular process. Remaining microbial
      contamination was cultured quantitatively. Nineteen objects were investigated in
      10 experiments each. Cleaning, measured as log reduction >5-6 of B. subtilis, was
      achieved on surfaces that were adequately in contact with the water flow in the
      machine. Disinfection (and cleaning) measured as log reduction >5-6 of E.
      faecalis was successful at all points examined. The test method is simple and
      quantifiable, and can be used to evaluate and to improve cleaning and
      disinfection processes.

PMID- 11469503
TI  - Expression of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in human chondrosarcomas.
AB  - The aim of the present study was to characterise the ability of malignant
      chondrosarcomas to invade normal bone by analysing their production of matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
      For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs
      for several MMPs and all 4 TIMPs by Northern hybridisation, and for
      immunohistochemical localisation of the proteins. A characteristic finding of
      these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in
      chondrosarcomas when compared with nonmalignant control samples. Individual
      chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs.
      The results of Northern hybridisations were supported by immunohistochemical
      stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further
      suggesting that these may have prognostic value for determining whether
      individual chondrosarcomas are locally aggressive or have a probability of
      recurrence. Another finding of the present study was a marked heterogeneity in
      histologic appearance and gene expression of the chondrosarcomas, emphasising the
      importance of analysing several areas of these tumours to get representative
      results. These findings suggest that analysis of MMPs could be a useful
      diagnostic indicator in patients with cartilaginous tumours and could help in
      differentiating between a low-grade malignant chondrosarcoma and a benign growing
      enchondroma.

PMID- 11469504
TI  - Epithelial-myoepithelial carcinoma harboring p53 mutation.
AB  - A case of epithelial-myoepithelial carcinoma of the parotid gland harboring p53
      mutation is reported. The tumor removed from a 67-year-old Japanese female was
      composed of an organoid biphasic population of cells: inner dark epithelial cells
      were surrounded by clear myoepithelial cells. The cells were immunopositive for
      EMA and smooth muscle actin, respectively. Some of the epithelial cells formed
      solid nests. Immunostaining for proliferating cell nuclear antigen (PCNA)
      resulted in a higher percentage of labeled cells in the solid epithelial region
      than in the region with the more general biphasic pattern. Genetic analysis,
      including polymerase chain reaction-single strand conformational polymorphism
      (PCR-SSCP) and nucleotide sequencing, revealed a mutation in codon 207 (aspartic
      acid to glycine) of the p53 tumor-suppressor gene. To our knowledge, this is the
      first report of a mutation in the p53 gene in an epithelial-myoepithelial
      carcinoma of the salivary gland.

PMID- 11469505
TI  - Comparative efficacy of various toxoids against salmonellosis in poultry.
AB  - An attempt was made to develop a vaccine against salmonellosis in poultry by
      formalizing the Salmonella toxins (enterotoxin plus cytotoxins) that have been
      found to be the main virulent products of the organisms. Formalized (FT) and
      carbonated (CT) toxoids were prepared from partially purified toxins of Salomella
      enteric subspecies enterica ser. Weltevreden (BM-1643) and S. enterica ser.
      Gallinarum (L-19/a). There was no mortality in birds vaccinated with formalized
      toxoid of serovar Weltevredenplus Freund's complete adjuvant (FCA) following
      homologous or heterologous (S. enterica ser. Gallinarum and S. enterica ser.
      Typhimurium) challenges. Protection ranged from 50% to 83.3% in thegroups
      immunized with other preparations of S. enterica ser. Weltevreden, i.e. with FT
      without FCA or with CT with or without FCA. Formalized toxoid prepared from S.
      entrica ser. Gallinarum (FTSG) toxins given with FCA afforded 100% protection
      against homologous challenge, but not against heterologous serovars. In the
      control group. only 16.7% of the birds survived in a subgroup challenged with S.
      enterica ser. Gallinarum. and none withstood challenge with S enterica ser.
      Weltevreden or S. enterica ser. Typhimurium. No untoward reactions were observed
      in any of the immunized groups. Thus, the vaccine was considered to be potent and
      safe.

PMID- 11469506
TI  - In vitro metabolism of 14C-moxidectin by hepatic microsomes from various species.
AB  - Moxidectin is an antiparasitic drug widely used in cattle, sheep and companion
      animals. No data were available on its metabolism in wild species or in
      monogastrics. The in vitro metabolism of 14C-moxidectin was studied using hepatic
      microsomes from several different species: cow (Bos taurus). sheep (Ovis ovis),
      goat (Capra hircus), deer (Cervus dama), rat (Rattus norvegicus), pig (Sus scrofa
      and rabbit (Oryctolagus cuniculus). After separation and quantification by HPLC,
      the extent of metabolism of 14C-moxidectin was greatest with microsomes from
      sheep (32.7%) as compared to those from cows (20.6%), deer (15.4%), goats
      (12.7%). rabbits (7.0%) or rats (3.0%). The least metabolism occurred with
      microsomes from pigs. with 0.8% of total detected metabolites. A C29
      monohydroxymethyl metabolite was detected in the greatest amounts. providing 0.4%
      out of the total detected radioactivity in pigs and 19.3% in sheep. In addition,
      the importance of P450 3A in the metabolism of 14C-moxidectin was confirmed by
      using in vivo induced P450 in combination with various P450 inhibitors.

PMID- 11469507
TI  - Effects of fosinopril on renal function, baroreflex response and noradrenaline
      pressor response in conscious normotensive dogs.
AB  - The blood pressure. renal function, baroreflex response of heart rate and
      noradrenaline (norepinephrine) pressor response were determined in conscious,
      normotensive, sodium-replete dogs that had received fosinopril. Oral
      administration of fosinopril at a dose of 1 mg/kg per day for 5 days decreased
      the systolic arterial pressure from 147.1 +/- 3 to 131.8 +/- 4.3 mmHg (p < 0.05)
      and the mean arterial pressure from 99.7+/- 3.9 to 87.5 +/- 2.8 mmHg (p < 0.05),
      while heart rate was unchanged. A study of the noradrenaline pressor response
      showed a tendency to alleviate the increased MAP by fosinopril treatment,
      although this was not significant. There were no significant changes in the
      sensitivity of the baroreflex response in HR, although the setpoint was reduced.
      After 7 days of fosinopril treatment, the glomerular filtration rate had
      increased by 18.5% (p < 0.05). The effective renal plasma flow tended to
      increase, leaving the filtration fraction unchanged. The renal vascular
      resistance was reduced by 11.3% (p < 0.05). Fosinopril caused a significant 41.5%
      increase in urinary excretion of Na+ (p < 0.05), along with an elevation of
      urinary excretion of K+ and Cl- . It is concluded that fosinopril can lower the
      blood pressure, reduce the noradrenaline pressor response and lower the cardiac
      baroreflex setpoint to noradrenaline. Oral administration of fosinopril for 7
      days affects both the renal haemodynamics and electrolyte excretions in
      conscious, normotensive, sodium-replete dogs.

PMID- 11469508
TI  - Some pharmacokinetic data for danofloxacin in healthy goats.
AB  - The pharmacokinetics of danofloxacin was determined in five clinically normal
      adult female goats after intravenous (IV) or intramuscular (IM) doses of 1.25
      mg/kg body weight. Blood and urine samples were collected from each animal at
      precise time intervals. Serum and urine concentrations were determined using
      microbiological assay methods and the data were subjected to kinetic analysis.
      After intravenous injection, the serum concentration time curves of danofloxacin
      were characteristic of a two-compartment open model. The drug was rapidly
      distributed and eliminated with half-lives of 17.71 +/- 1.38 min and 81.18 +/-
      3.70 min, respectively. The drug persisted in the central, highly perfused organs
      with a K12/K21 ratio of 0.67 +/- 0.25. The mean volume of distribution at a
      steady state (Vdss was 1.42 +/- 0.15 L/kg. After intramuscular administration,
      the serum concentration peaked after 0.58 +/- 0.04 h at approximately 0.33 +/-
      0.01 microg/ml. While danofloxacin could be detected in serum for 4 and 6 h, it
      was recovered in urine for up to 24 and 72 h after IV and IM administration,
      respectively. The systemic bioavailability after IM injection was 65.70% +/-
      10.28% and the serum protein-bound fraction was 13.55 +/- 1.78%.

PMID- 11469509
TI  - Physiopathological effects of the administration of chronic cyanide to growing
      goats--a model for ingestion of cyanogenic plants.
AB  - Ingestion of cyanogenic plants, such as cassava and sorghum, has been associated
      with goitre and tropical pancreatic diabetes in both humans and animals. Thus,
      the objective of the present study was to determine the toxic effects on the
      thyroid and pancreas in growing goats of prolonged exposure to potassium cyanide
      (KCN). Thirty-four male goats were divided into five groups dosed with KCN at 0
      (control). 0.3, 0.6, 1.2 or 3.0 mg/kg daily for 5 months. Blood samples were
      obtained in order to determine the glucose, cholesterol, thyroxine (T4),
      triiodothyronine (T3) and thiocyanate concentrations and for haematological
      studies; pancreas and thyroid gland were collected for histopathological study.
      The group receiving the highest dose of cyanide showed lower body weight gains
      and carcase weights and a decrease in plasma T3 concentrations compared to the
      control group. Reabsorption vacuoles in follicular colloid and normocytic
      normochromic anaemia were observed in the experimental animals. Inhibition of
      peripheral conversion of T4 to T3 is suggested. However, no diabetogenic effects
      were observed.

PMID- 11469510
TI  - The pharmacokinetics of a long-acting oxytetracycline formulation in healthy dogs
      and in dogs infected with Ehrlichia canis.
AB  - The pharmacokinetic properties of oxytetracycline were studied following a single
      injection of a long-acting formulation (20 mg/kg body weight) into the
      semimembranosus muscle of healthy dogs and of dogs that had been experimentally
      infected with Ehrlichia canis. The disposition curves of the long-acting
      oxytetracycline formulation before and after infection were best described by a
      bi-exponential decline after a first-order absorption. The mean maximum serum
      concentration (Cmax) following infection was significantly lower and the time
      taken to attain this concentration (tmax) was significantly shorter than that in
      the healthy dogs. The mean apparent elimination half-life (t(1/2) beta) was
      significantly increased following infection. The corresponding rate constant
      (beta) was significantly decreased. The absorption half-life (t(1/2) ab) was
      significantly decreased after infection. The volume of distribution at steady
      state (Vdss) increased significantly following infection. It was concluded that
      the pharmacokinetic behaviour of a long-acting oxytetracycline in dogs after
      intramuscular administration is characterized by a two-compartment model with a
      slow elimination phase. This could be due to flip-flop kinetics. The febrile
      reaction in experimental E. canis infection affected some pharmacokinetic
      parameters of oxytetracycline.

PMID- 11469511
TI  - The variability and repeatability of indices derived from the single-breath
      diagram for CO2 in horses with chronic obstructive pulmonary disease and the
      effect of lobelin hydrochloride on these indices.
AB  - Several indices of ventilatory heterogeneity can be identified from the
      volumetric capnogram and its graphic presentation, the single-breath diagram for
      CO2 (SBD-CO2). Physiologically based indices of pulmonary function (VTE, VCO2,
      FACO2, VDBohr% VDBohr%, VD/VTE, A1/A2) were calculated for healthy horses (group
      I, n = 5) and for horses with subclinical (group II, n = 7) or clinically
      manifest chronic obstructive pulmonary disease (COPD) (group III, n = 8) during
      tidal breathing and after medication with lobelin hydrochloride (Lobelin). We
      investigated the variability and repeatability of the lung function indices in
      healthy horses and in those with COPD both during tidal breathing and after
      administration of Lobelin, a centrally acting respiratory stimulant. In
      particular, we were interested in whether the discriminating ability of SBD-CO2
      derived lung function indices would be increased between different patient groups
      after administration of Lobelin compared to those for the resting values. Of the
      indices studied, VTE, FACO, VDBohr% and A1/A2 appeared to be those with good to
      excellent repeatability in discriminating healthy horses from those with COPD.
      Stimulating respiration with Lobelin gave no advantage in the repeatability of
      the lung function indices or in differentiating between horses with different
      degrees of COPD.

PMID- 11469512
TI  - A preliminary study on the carcinogenicity of the common fern Onychium contiguum.
AB  - Onychium contiguum (Family Cryptogrammaceae) is a common terrestrial fern in the
      Himalayas and in many other parts of the world. It is also present on the
      pastures in areas where grazing animals suffer from bovine urinary bladder
      cancer. This fern is occasionally grazed by animals and in some areas it is
      present as a contaminant in grasses stored for winter feeding. Certain species of
      the genus Onychium are used in folk medicine. Long-term exposure of experimental
      animals to O. contiguum appeared to cause tumours of the ileum. urinary bladder
      and mammary glands.

PMID- 11469513
TI  - The use of a Daphnia magna bioassay for rapid screening of acute intoxications
      with insecticides in dogs and cats.
AB  - Sudden death due to acute insecticide intoxications occurs frequently in dogs and
      cats. The absence of characteristic lesions at autopsy often renders post-mortem
      diagnosis dependent on the analysis of samples taken from the carcase at autopsy.
      In the present study, a bioassay utilizing Daphnia magna was proposed and tested
      as a rapid screening method for acute intoxications in dogs and cats. The
      bioassay was shown to be highly sensitive for detecting carbamate and
      organophosphate insecticides in the stomach contents. Generally. the mean
      survival time of the waterfleas in the control group was 5.17 h (SD = 1.24) and
      in the intoxicated group 1.32 h (SD = 1.49). during a 6 h observation period. If
      a cut-off is set at 4 h, this Daphnia bioassay gave 5.5% false negative results
      and 18.2% false positive results. using the results of toxicological analyses as
      a gold standard.

PMID- 11469514
TI  - One-step RT-PCR for the detection of infectious bursal disease virus in clinical
      samples.
AB  - A single-tube, non-interrupted, one-step RT-PCR has been standardized to amplify
      the hypervariable region of the VP2 gene sequence of infectious bursal disease
      virus (IBDV). The technique standardized on purified viral RNA was successfully
      applied to the detection of the virus directly in clinical samples. The amplified
      products were confirmed to be IBDV specific by their size in ethidium bromide
      stained agarose gel, nested PCR and restriction enzyme digestion. Digestion of
      the amplicons with StyI restriction enzyme also differentiated classical virus
      from six very virulent field isolates. The sensitivity of the one-step RT-PCR was
      found to be 0.2 pg of viral RNA.

PMID- 11469515
TI  - The treatment of Sjogren's syndrome patients with pilocarpine-tablets.
AB  - Therapeutic progress in Sjogren's syndrome has lagged behind our recognition and
      understanding of clinical manifestations and disease pathogenesis. Past treatment
      of sicca symptoms with immunosuppressives has been unsuccessful. The use of
      secretagogues (e.g. pilocarpine-HCl) to stimulate flow from exocrine glands
      represents a novel approach that has dramatically altered our management strategy
      for Sjogren's syndrome. Clinical studies with pilocarpine (Salagen) tablets in
      the United States have demonstrated significant subjective and objective benefit
      for xerostomia and related oral symptoms at doses of 20 mg/day or more.
      Symptomatic relief of xerophthalmia and other xeroses due to Sjogren's syndrome
      may also occur. Data from human and animal models suggest that regular use of
      pilocarpine may not only improve patient quality of life but potentially prevent
      complications as well. Better methods of patient selection for therapy are needed
      since clinical response to pilocarpine cannot be predicted based on the duration
      of patient symptoms.

PMID- 11469516
TI  - New criteria for diagnosing Sjogren's syndrome: a step forward?--or...
AB  - Primary Sjogren's syndrome seems to be the most common of the chronic systemic
      inflammatory connective tissue diseases, according to epidemiological
      investigations. Basic and clinical research, including treatment within this
      group, is increasing while simultaneously there is increasing confusion and
      uncertainty about the classification criteria for Sjogren's syndrome. Within the
      last three decades nine different classification criteria sets have been
      introduced including the recent US-European classification criteria set. The
      diagnostic criteria used in daily practice seem to differ even more and many
      forget that the function of both the lachrymal glands and the salivary glands
      should be diminished. Consequently many rheumatologists prefer to diagnose
      patients according to classification criteria. The advantages and disadvantages
      of the various classification criteria for primary Sjogren's syndrome are dealt
      with but it is stressed that the majority of these will exclude former/present
      smokers (from the diagnoses)--more than half of the population!

PMID- 11469517
TI  - Monitoring the disease activity.
AB  - Primary Sjogren's syndrome is a chronic systemic rheumatic disease characterized
      as an autoimmune exocrinopathy or autoimmune epithelitis thereby suggesting a
      pathogenesis leading to tissue specific autoimmune lesion. The development of
      internationally approved criteria for the classification and diagnosis of
      Sjogren's syndrome has been a major scientific task for nearly two decades with
      consensus now approaching. In contrast, an international dialogue on how to
      develop additional common criteria for the assessment of disease activity, organ
      damage and outcome in Sjogren's syndrome has just recently been initiated. Such
      assessment criteria would provide useful measures for patient management and are
      mandatory for comparing efficacy between different clinical trials. The lack of
      common assessment criteria may be explained by missing uniform diagnostic
      criteria, by the multispeciality and systemic nature of the disease and the
      difficulties in separating out what is activity and what is damage in Sjogren's
      syndrome. Attempts are now made to overcome these problems. The purpose of this
      paper is to give a brief introduction to the concepts of disease activity, damage
      and outcome in Sjogren's syndrome with reference to the results obtained from a
      recent workshop on assessment tools in Sjogren's syndrome held in Oxford, England
      in March 2000.

PMID- 11469518
TI  - Sjogren's syndrome as seen by an ophthalmologist.
AB  - Ocular surface involvement is a frequent feature of Sjogren syndrome
      characterized by the presence of typical symptoms such as burning and foreign
      body sensation and by wide spread epithelial damage of the cornea and on the
      conjunctiva. There is now evidence that local inflammatory changes and lacrymal
      gland-derived tear-borne pro-inflammatory agents have an important role in the
      build up and the maintenance, of ocular surface damage by the instauration of
      self maintaining vicious cycles. Inflammation causing decreased ocular surface
      sensation, resulting in further decreased tear secretion and decreased tear
      clearance, with growing concentration of pro inflammatory agents on the ocular
      surface. From the anatomic pathological point of view there is a not clarified
      discrepancy between the early highly depressed tear fluid production and the
      limited extension of involvement of the lacrymal gland. Proper gland stimulatory
      agents and control of inflammation could result in a better treatment than the
      palliative therapy available to day.

PMID- 11469519
TI  - Sjogren's syndrome as seen by an oral physician.
AB  - This article provides a brief overview of the various orofacial presentations of
      Sjogren's syndrome. The paper summarises the clinical features of patients with
      xerostomia, and alludes to differential diagnosis, investigative procedures and
      therapeutic modalities for the oral component of Sjogren's syndrome.

PMID- 11469520
TI  - Antinuclear antibody screening in this new millennium: farewell to the
      microscope?
AB  - ANA testing by immunofluorescence technique (F-ANA) is nowadays still performed
      in much the same way as 45 years ago when the test was introduced. Due to its low
      specificity the F-ANA test has a poor predictive value for systemic autoimmune
      diseases and in addition has proven difficult to standardise. In the meantime,
      many of the nuclear and cytoplasmatic auto-antigens, related to specific types of
      autoimmune disease, have been characterised and can be tested for in specific
      ELISA assays (E-ANA). These assays are in large part automated and enable the
      large volume testing required, by the current attitude, to use ANA-testing for
      its high negative predictive value in the exclusion of systemic autoimmune
      disease. In addition, E-ANA assays give specific results for clinically relevant
      autoantibodies, while its test repertoire can be altered at any given time to
      reflect changes in current thinking on relevant auto-antigens. Thus, we suggest
      that the unspecific F-ANA test should no longer be considered the gold standard
      for the detection of clinically relevant autoantibodies.

PMID- 11469521
TI  - Folate supplementation during methotrexate treatment of patients with rheumatoid
      arthritis. An update and proposals for guidelines.
AB  - The efficacy of weekly low-dose methotrexate treatment of rheumatoid arthritis is
      well documented. Efficacy and adverse effects are both dose dependent. and
      adverse effects rather than lack of efficacy are the main reason for
      discontinuing therapy. Several adverse effects are related to folate
      deficiencies, largely due to the antifolate properties of methotrexate. In order
      to reduce adverse effects without compromising drug efficacy, numerous clinical
      investigations have been performed using supplementation with folic or folinic
      acid during methotrexate therapy of patients with rheumatoid arthritis,
      addressing both the timing of folate supplementation and the weekly folate-to
      methotrexate ratio. Based on these studies, an individually adjusted supply of
      folic acid rather than folinic acid is proposed. For many patients, however, a
      properly balanced diet is sufficient to avoid folate deficiency.

PMID- 11469522
TI  - Slowing of disease progression in rheumatoid arthritis patients during long-term
      treatment with leflunomide or sulfasalazine.
AB  - Radiographic disease progression with leflunomide and sulfasalazine treatment was
      assessed in rheumatoid arthritis patients in a double-blind trial that was
      placebo controlled for the first 6 months. Completers at 6 months opted to
      continue on 12- and 24-month double-blind extensions; patients in the placebo
      group were switched to sulfasalazine. Changes in Larsen scores were assessed in
      evaluable patient cohorts at 6 (n=228), 12 (n=136), and 24 (n=65) months. Changes
      in Larsen scores and erosive joint counts with leflunomide and sulfasalazine at 6
      months showed significantly less radiographic progression than placebo. Sustained
      retardation of radiographic progression was seen in the 24-month intent-to-treat
      cohorts (delta Larsen scores: leflunomide -0.07, sulfasalazine -0.03). Changes in
      erosive joint counts within the 24-month leflunomide cohort suggest halting of
      disease progression for patients who continued in the study for 2 years
      (leflunomide -0.92, sulfasalazine 0.80). Leflunomide was well tolerated with no
      unexpected adverse events during the 2-year period. This study demonstrates that
      slowing of disease progression with leflunomide, observed as early as 6 months,
      is maintained long term in patients who complete 2 years of treatment.

PMID- 11469523
TI  - Effect of treatment on the outcome of very early rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the effect of treatment on the outcome of very early RA.
      METHODS: In a 3-year prospective study of 27 patients with very early RA (VERA)
      (symptoms <4 months before diagnosis) and 122 patients with early RA (symptoms
      between 4-24 months) the effect of active treatment on the clinical picture,
      functional capacity, and radiological progression was evaluated. RESULTS:
      Initially VERA patients had a more active clinical picture and worse functional
      capacity. Despite a higher number of DMARDs used in VERA patients, C-reactive
      protein and Ritchie index remained significantly higher in these patients
      (although significant improvement occurred). They also had a more rapidly
      progressive disease (higher Larsen score/month of symptoms) during pre-treatment
      period, the progression of which was retarded with early, active DMARD therapy.
      By the end of 3 years, the rate of progression ran parallel in both groups.
      CONCLUSION: Active treatment had an impact on the rate of radiological
      progression and clinical activity but not on the functional outcome in patients
      with initially active RA of short duration.

PMID- 11469524
TI  - Long-term results of wrist arthrodeses fixed with self-reinforced polylevolactic
      acid implants in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Implants made of self-reinforcing polylevolactic acid (SR-PLLA) have
      been successfully used in arthrodeses of patients with rheumatoid arthritis. No
      lone-term evaluation on bioabsorbable fixation in patients with rheumatoid
      arthritis has been published so far. METHODS: In this study 21 wrist fusions were
      performed on 18 patients with rheumatoid arthritis by using SR-PLLA rods as
      fixation devices. The follow-up time was 3-8 years (mean 5.4 years). RESULTS: The
      results showed one non-union but no infections or problems associated with the
      bioabsorbable implants used. CONCLUSION: According to this study, fixation of
      wrist arthrodesis in patients with rheumatoid arthritis can be performed by using
      SR-PLLA implants with favourable results. The benefit of this method is the
      avoidance of the removal operation of fixation devices.

PMID- 11469525
TI  - Extraction and validation of a lower limb HAQ by comparison with objective
      measurement of ambulatory activity.
AB  - OBJECTIVES: Both the Health Assessment Questionnaire (HAQ) and the measurement of
      spontaneous ambulatory activity are measures that can be used to evaluate
      disability in RA. METHODS: A cross sectional survey was conducted of 105 RA
      patients where the HAQ was compared with ambulatory activity from the Numact
      monitor. Rank correlation was used to evaluate the relationships between activity
      and the complete and individual sections of the HAQ. RESULTS: Correlation of
      activity with total HAQ produced significant results (r= -0.29 to -0.48).
      Correlation with individual sections showed the strongest association with
      "Hygiene", followed by "Activities", and "Walking". A lower limb HAQ was devised
      using these and the dressing and rising items. CONCLUSIONS: HAQ and recorded
      activity measure different but related aspects of disability. Activity should be
      used if the ability to quantify the result outweighs the extra effort involved in
      the study.

PMID- 11469526
TI  - Decreased production of interleukin-12 and interferon-gamma is associated with
      renal involvement in systemic lupus erythematosus.
AB  - OBJECTIVE: To analyze the type 1/type 2 cytokine balance in patients with
      systemic lupus erythematosus (SLE) according to the presence of renal disorder
      and activity status. METHODS: We measured the serum levels of type 1 (IFN-gamma,
      IL-12) and type 2 cytokines (IL-4, IL-10) as well as spontaneous and stimulated
      cytokine production from peripheral blood mononuclear cells (PBMC) in 40 patients
      with SLE. RESULTS: Patients with lupus nephritis (LN) showed significantly lower
      levels of serum IL-12 and IFN-gamma than those without LN. Production of IL-12
      and IFN-gamma by stimulated PBMC were also decreased in patients with LN. The
      circulating IL-12 correlated positively with IFN-gamma, but inversely with IL-10.
      The SLEDAI scores correlated well with the ratio of IL-4/IFN-gamma levels.
      CONCLUSION: The reduced production of IL-12 and IFN-gamma and the resultant shift
      towards the type 2 cytokine phenotype may be associated with LN.

PMID- 11469527
TI  - Serglycin expression in CD2+ and CD14+ cells from patients with various rheumatic
      diseases.
AB  - The objective of the study was to look at the in vivo expression of serglycin in
      cells taken from patients with an inflammatory disease. The mRNA expression of
      the small proteoglycan serglycin was investigated in macrophages/monocytes and T
      cells derived from the synovial fluid and blood of six patients with various
      rheumatic diseases and from the blood of two control subjects. Our results
      demonstrate higher Levels of expression in CD14+ cetts taken from patients with
      chronic inflammatory diseases than in control subjects. This suggests that
      serglycin may play a role during the inflammatory process.

PMID- 11469528
TI  - Anti-IL-1alpha autoantibodies in early rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the potential predictive value of autoantibodies
      against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis
      (RA). METHOD: Anti-IL-1alpha were assessed by radioimmunoassay in sera from 164
      patients with early RA. RESULTS: At baseline, anti-IL-1alpha were detected in 52
      (32%) of the patients. After 2 years, the entire patient material showed
      significant clinical improvement (DAS28, CRP, HAQ, and pain- VAS) while there was
      an overall radiological progression (Larsen score). The group of patients with
      anti-IL-1alpha and the group of patients without this antibody showed similar
      disease development in disease activity, function, and joint destruction and
      there were no statistically significant differences between the two groups,
      neither at baseline nor at end-point. CONCLUSION: The present data do not lend
      support to previous observations that anti-IL-1alpha may be a marker for less
      destructive RA. However, a predictive value of this antibody over longer time
      periods cannot be ruled out by this two year study.

PMID- 11469529
TI  - Non-insulin dependent diabetes mellitus (NIDDM) and patterns of osteoarthritis.
      The Ulm osteoarthritis study.
AB  - OBJECTIVES: Despite recent advances regarding the role of diabetes with respect
      to cartilage metabolism, epidemiologic data to quantify the role of diabetes in
      the development of osteoarthritis (OA) are sparse. METHODS: OA patterns were
      studied in 809 patients with knee or hip joint replacement due to OA. NIDDM was
      defined by a history of physician diagnosed diabetes or use of
      antihyperglycemics. RESULTS: Patients with NIDDM had more often bilateral OA
      (adjusted odds ratio (OR)=2.2; 95% confidence interval (CI): 0.8-6.4). No
      association between NIDDM and generalized OA (adjusted OR= 1.0; 95%CI: 0.5-1.9)
      was observed. CONCLUSIONS: Our results are consistent with the hypothesis that
      NIDDM might be a potentially important systemic risk factor for knee and hip OA,
      but chance cannot be ruled out as an alternative explanation.

PMID- 11469530
TI  - Anti-cardiolipin antibodies, Raynaud's phenomenon with digital ischemia, and non
      small cell carcinoma of the lung.
AB  - Raynaud's phenomenon, digital ischemia, antinuclear antibodies and
      anticardiolipin antibodies are uncommon features of malignancy. The association
      of all of these in a patient with malignancy has not previously been reported. We
      describe a 52 year old woman with non small-cell carcinoma of the lung who also
      had Raynaud's phenomenon, digital ischemia, anti-nuclear antibodies and
      anticardiolipin antibodies.

PMID- 11469531
TI  - Psoriatic arthritis and alpha-interferon.

PMID- 11469532
TI  - Ultrasound evaluation of plantar fasciitis.

PMID- 11469533
TI  - Anti-cardiolipin autoantbodies and pulmonary embolism.

PMID- 11469534
TI  - Immunoelectron microscopic study of PECAM-1 expression on lymphatic endothelium
      of the human tongue.
AB  - The expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) on
      lymphatic and blood vessels of the human tongue was examined with fluorescence
      and transmission electron microscopy (TEM). The study used anti-desmoplakins
      antiserum for light microscopic identification of the lymphatic vessels, plus a
      pre-embedding immunogold electron microscopic technique for TEM observations.
      Before making TEM observations, cryostat serial sections were immunostained with
      anti-desmoplakins or anti-PECAM-1 and then embedded. Semithin sections from each
      cryostat section were photographed under a light microscope and compared in order
      to identify the lymphatic vessels expressing PECAM-1. In fluorescence microscopy,
      PECAM-1 expression on lymphatic vessels was weaker than that on blood vessels.
      TEM observations showed that PECAM-1 expression on the blood vessels was observed
      only on the luminal surface of the endothelium. In lymphatic vessels, PECAM-1
      expression was found both on the luminal and abluminal surfaces of the
      endothelium. The density of the PECAM-1 reaction products was lower in lymphatic
      vessels than in blood vessels. The density of PECAM-1 reaction products on the
      luminal surface of lymphatic vessels was higher than on the abluminal surfaces.
      The results suggest that blood vessels are more active than lymphatic vessels in
      leukocyte migration. The expression of PECAM-1 on the abluminal surface of
      lymphatic endothelium may allow leukocytes to adhere to the endothelium and
      interact in their migration from tissue into lymphatic vessels.

PMID- 11469535
TI  - Heterogeneity of bladder myocytes in vitro: modulation of myosin isoform
      expression.
AB  - We studied the expression of myosin heavy chain isoforms differing at the N
      terminal (SM-A, SM-B) and the C-terminal (SM1, SM2) regions and non-muscle myosin
      heavy chain II-A and II-B (NMMHC II-A and B) in newborn and adult rabbit bladder
      smooth muscle cells (SMCs) and in cultures of enzymatically dissociated neonatal
      detrusor. RT-PCR analyses revealed that 94.5+/-3.27% of MHC transcripts of the
      adult bladder SMCs contained the 21-nucleotide insert (SM-B) compared with 83.8+/
      3.2% in the newborn bladder, with the remainder of the mRNA being non-inserted
      (SM-A). In 3, 7, and 10 days of primary culture (proliferating, confluent, and
      post-confluent, respectively) and up to 4 subculture passages, bladder myocytes
      expressed predominantly SM-A. Immunofluorescence microscopy revealed
      heterogeneity in cultured myocytes, i.e. SM-B positive cells coexisting with
      negatively stained cells. In adult bladder, the C-terminal isoforms SM1 and SM2
      represented, 43.1+/-4.3% and 56.89 + 4.3% of the mRNA, respectively, while
      newborn bladders expressed 72.5+/-7% SM1 and 27.5+/-7% SM2. Upon culturing, cells
      predominantly expressed SM1 at both the mRNA and protein levels. NMMHC II-A was
      expressed by both adult and newborn bladders and in culture, whereas NMMHC II-B
      was expressed at low levels only in newborn bladders, but upregulated in culture.
      These data indicate that bladder myocytes in vitro undergo modulation with
      relative overexpression of SM-A and SM1 and upregulation of NMMHC II-B.
      Information on the mechanisms responsible for this modulation in vitro might
      provide an understanding of the nature of altered myosin isoform expression
      associated with smooth muscle dysfunction in certain bladder diseases.

PMID- 11469536
TI  - Interleukin-1beta-induced type IIA secreted phospholipase A2 gene expression and
      extracellular activity in rat vascular endothelial cells.
AB  - Two phospholipase A2 (PLA2) isoforms, secretory and cytosolic, have been
      implicated in inflammation. Secretory type IIA PLA2 (sPLA2-IIA), which hydrolyzes
      fatty acids bound at the sn-2 position of glycerophospholipids, has been detected
      universally in a variety of mammalian tissues and cells. The expression of the
      sPLA2-IIA gene and its extracellular activity were shown to be regulated by
      different factors such as hypoxia, cytokines and phorbol esters. In the present
      study, we examined the effects of interleukin-1beta (IL-1beta) on the expression
      of the 14kDa sPLA2-IIA, determined using reverse transcription polymerase chain
      reaction and radiometric Escherichia coli enzyme assay in primary cultures of rat
      endothelial cells and in two different rat endothelial cell lines (SVAREC and
      RBE4). These experiments revealed that IL-1beta induces sPLA2-IIa gene expression
      and secretion of the enzyme in endothelial cells in a dose- and time-dependent
      manner. The cAMP-elevator forskolin did not augment the cytokine-induced
      elevation of sPLA2-IIa enzyme activity but significantly increased the IL-1beta
      stimulated sPLA2-IIa mRNA contents in endothelial cells.

PMID- 11469537
TI  - Ultrastructural aspects of oogenesis and oocyte primary growth in Serrasalmus
      spilopleura (Teleostei, Characiformes, Characidae).
AB  - The ultrastructural characteristics of the organelles present in Serrasalmus
      spilopleura oogonia and oocytes undergoing primary growth were described in
      detail, considering its role in the nuclear and cytoplasmic metabolic processes
      that occur in these cell types. Even though these cells do not significantly
      differ from those similar to them that are found in other teleost groups, the
      analysis of their ultrastructure makes available new data on the reproductive
      biology of Characiformes.

PMID- 11469538
TI  - Acute food restriction increases collagen breakdown and phagocytosis by mature
      decidual cells of mice.
AB  - An ultrastructural study was undertaken on antimesometrial mature decidual tissue
      of fed and food-restricted mice, on day 9 of pregnancy. The mean ad libitum food
      intake was established on mice from the 8th till the 9th day of pregnancy. Fed
      mice were used as controls. Experimental animals were divided into two groups:
      one was allowed to feed 25% of normal diet and the other 50%. Extracellular
      collagen fibrils were scarce in fed animals and conspicuous in food restriction.
      Granular electron-dense deposits and filamentous aggregates of disintegrating
      collagen fibrils were observed in all food-deprived mice but were rarely noted in
      fed animals. Intracellular vacuolar structures exhibited other typical cross
      banded collagen immersed in finely granular electron-translucent material (clear
      vacuole) or electron-dense material containing collagen fibrils with a faint
      periodicity (dark vacuole). The clear and dark vacuoles were scarce in fed
      animals and evident in food-restricted mice, mainly in those 25% food restricted.
      Although collagen breakdown may be part of the normal process of decidual tissue
      remodelling our results suggest that it is enhanced in food-restricted animals.
      Thus it seems that collagen breakdown is a normal mechanism that may be regulated
      by the food intake of the pregnant animal.

PMID- 11469539
TI  - Ectosymbiotic bacteria on ciliated cells of a rotifer.
AB  - During the examination of Brachionus plicatilis (Rotifera, Monogononta),
      ectosymbiotic bacteria were found in the ciliated buccal region. These have about
      the same dimensions as the cilia and possess a specific apical region that
      apparently serves to attach the bacterium to its host cell. This apical region
      resembles a vesicle but is interpreted as a specialized region of the bacterial
      nucleocytoplasm devoid of ribosomes and chromatin strands but containing a
      crystalline rod. The bacterium has two membranes (as have other Gram-negative
      bacteria) also over the apical region. Thin strands join the two membranes and
      similar strands extend from the bacterium to the cell membrane of the host cell.
      No intracellular bacteria were found in this study.

PMID- 11469540
TI  - Effects of androgen deprivation on the histology of adult chimpanzee testis.
AB  - Until primate sperm are exposed to the unique microenvironment of the epididymis,
      they are not capable of fertilization or vigorous motility. Many of the proteins
      that contribute to the unique microenvironment of the primate epididymis, and
      thus to sperm maturation, are dependent on androgens to induce their synthesis
      and secretion. GnRH antagonists have proved effective in suppressing LH and
      testosterone synthesis and secretion, and thus in maintaining a state of androgen
      deprivation or functional hypogonadotropism. We report here the effects of GnRH
      antagonist-induced androgen-deprivation on the histology of the testicular
      interstitium and seminiferous epithelium of the adult male chimpanzee. After only
      21 days of androgen-deprivation, chimpanzee testicular tissues exhibit specific
      atrophic changes, including the loss of contact between developing spermatocytes
      and between Sertoli cells and their developing spermatids, alterations in cell
      development resulting in missing maturation steps (elongating Sc and structurally
      complete Sd2 spermatids) and inappropriate cell associations, varying degrees of
      cytoplasmic degradation in germ cells, Sertoli cells, and Leydig cells, and a
      tubular lumen obscured by masses of sloughed primary and secondary spermatocytes
      and what appear histologically to be Sb1 and Sd1 spermatids.

PMID- 11469541
TI  - Histological observations on transovarial transmission of a yeast-like symbiote
      in Nilaparvata lugens Stal (Homoptera, Delphacidae).
AB  - Transovarial transmission of a yeast-like symbiote (YLS) in the brown
      planthopper, Nilaparvata lugens Stal, was observed with light and electron
      microscopy. Light micrographs showed that there was no YLS in testes and
      spermathecae of the mated females, indicating that sperm is not involved in the
      transovarial transmission of the symbiote. Both light and electron micrographs
      showed the processes of YLS transmission from fat body to the oocyte. In females,
      the symbiotes in mycetocytes moved out of the syncytium, which is formed from a
      layer of fat body cells, by exocytosis, and released into hemocoel. Then, the
      free YLS in hemolymph approached to the ovarioles near pedicel and were enclosed
      by follicle cells. They entered the follicle cells around the primary oocyte by
      endocytosis at epithelial plug of the ovariole. The YLS aggregated at the
      posterior end of the mature egg after entering, and finally formed a symbiote
      ball.

PMID- 11469542
TI  - Succession of events in desquamation of superficial urothelial cells as a
      response to stress induced by prolonged constant illumination.
AB  - The effect of moderate stress induced by prolonged illumination was analysed on
      urothelial cells of female mouse urinary bladders at ultrastructural and
      cytochemical levels. This study demonstrates that the urothelium responds to
      moderate stress with desquamation which involves two subsequent steps. The first
      step includes a local detachment of tight junctions and consequently the loss of
      the permeability barrier leading to expanded intercellular spaces among
      urothelial cells. During the second step, the disjunction of desmosomes
      accompanied by exocytosis of lysosomal enzymes (NADPase) in the intercellular
      space results in exfoliation of superficial cells. It is evident that moderate
      stress elicits an enhanced desquamation of only superficial cells by a subsequent
      dysfunction of first tight junctions and after that adherens-type junctions. A
      rapid restoration of the new tight junctions prevents a long-term malfunction of
      the blood-urine barrier.

PMID- 11469543
TI  - Nuclear changes and acrosome formation during spermiogenesis in Euchistus heros
      (Hemiptera: Pentatomidae).
AB  - Ultrastructural and cytochemical studies were carried out on nuclear changes and
      acrosome formation during the spermiogenesis of the phytophagous bug Euchistus
      heros. The development of the nucleus involves changes in the shape and in degree
      of chromatin condensation: initially it is dispersed and with a low-electron
      density, then assumes a fibrillar arrangement and finally compacts in an electron
      dense material. The acrosome is formed by the Golgi complex and presents unusual
      morphological features during its development. The reaction product of acid
      phosphatase, glucose-6-phosphatase and thiamine pyrophosphatase activities were
      detected during various stages of acrosome development. In contrast, residues of
      alpha-N-acetylgalactosamine and basic proteins were only reported in the
      intermediate and late stages of the differentiation process, respectively.

PMID- 11469544
TI  - Effect of hyaluronic acid on human chondrocyte cell lines from articular
      cartilage.
AB  - The effects of hyaluronic acid (HA) derivative on the proliferation and
      metabolism of human chondrocytes were examined. Cells were obtained from
      cartilage from metatarsal phalangeal joints of 20 adult humans (aged 22-63) and
      from femoral knee condyles of 10 subjects (aged 22-77). Chondrocytes isolated by
      collagenase/Dnase digestion were cultured with addition of different doses of HA
      for 4 weeks. Morphological studies demonstrated that HA enhanced the adhesion of
      cells to substrate; HA-treated chondrocytes proliferated better than chondrocytes
      cultured in HA-free medium. This study shows that HA improves in vitro substrate
      adhesion ability and proliferative activity of human cartilage cells and that the
      response to the treatment varies on an individual basis.

PMID- 11469545
TI  - Ultrastructure of apyrene and eupyrene spermatozoa from the seminal vesicle of
      Euptoieta hegesia (Lepidoptera: Nymphalidae).
AB  - The ultrastructure of the seminal vesicle's spermatozoa of the butterfly
      Euptoieta hegesia was analyzed. The apyrene spermatozoa measure about 300 microm
      in length and swim freely in a secretion. The anterior end consists in a cap with
      a cylindrical extension and a globular structure. The flagellum has a 9+9+2
      axoneme, two mitochondrial derivatives with paracrystalline matrices and an
      external coat formed by concentric layers. The eupyrene spermatozoa measure about
      550 microm in length and are grouped into bundles. The anterior end consists in
      an amorphous globule. Posterior to this globule, a coat with a dense material
      covers the spermatozoon where an acrosome and a nucleus appear. The flagellum has
      a 9+9+2 axoneme and two mitochondrial derivatives. External to the coat and
      attached to the dense material, there is a reticular appendage, which has a
      paracrystalline core and extends to the distal tip of the spermatozoon.

PMID- 11469546
TI  - Evaluation of a pneumatically operated captive bolt for stunning/killing broiler
      chickens.
AB  - 1. Two separate experiments were carried out in this study. In experiment 1, the
      effectiveness of stunning broilers, as determined from physical responses, with a
      6 mm diameter bolt and an air line pressure of 827 kPa, when fired at 90 degrees
      (perpendicular to the skull) 110 degrees, 120 degrees and 130 degrees (leaning
      towards beak) was evaluated. 2. In experiment 2, the effects of perpendicular
      shooting with two bolt diameters (3 and 6 mm) and two air line pressures (620 and
      827 kPa) on spontaneous behaviour, electroencephalogram (EEG) and visually evoked
      potentials (VEPs) were evaluated in broilers. 3. Only the perpendicular shooting
      was effective in stunning/killing broilers (n= 10) as indicated by the immediate
      cessation of breathing and loss of neck muscle tension and eye reflexes.
      Deviations from the perpendicular shooting failed to stun 5 out of 9 broilers.
      The perpendicular vs non-perpendicular effect was significant. 4. Shooting
      broilers with a 3 mm bolt at air line pressures of 620 kPa (n=2) or 827 kPa (n=2)
      failed stun as indicated by the unaltered physical reflexes, EEG and VEPs.
      Shooting of two broilers with a 6 mm bolt at 620 kPa resulted in effective
      stunning and a very rapid recovery of consciousness in one bird and death in the
      other. 5. Captive bolt stunning of broilers with a 6 mm bolt and air line
      pressure of 827 kPa resulted in an immediate stun leading to death in all 6
      broilers tested. In these broilers, a profound EEG suppression and abolition of
      VEPs occurred immediately after shooting. 6. It is suggested that the appropriate
      variables for captive bolt stunning of broilers are a minimum of 6 mm bolt
      diameter driven at an air line pressure of 827 kPa and a penetration depth of 10
      mm.

PMID- 11469547
TI  - Environmental factors associated with rodent infestations in Argentine poultry
      farms.
AB  - 1. Seasonal variations in rodent infestations were studied at poultry farms in
      central Argentina as well as the environmental factors associated with rodent
      infestations at poultry farms. 2. During the summer and winter of 1998 rodent
      infestation was monitored at 10 poultry farms by means of tracking stations, and
      21 environmental variables were selected that a priori could be related with the
      extent of rodent infestation. 3. There was a higher rodent infestation in winter
      than in summer. 4. Species detected by rodent sightings at the poultry farms
      included Akodon azarae, Calomys spp. (C. laucha and possibly C. musculinus) and
      Mus musculus. 5. In summer, rodent infestation was positively associated with the
      perimeter of the farm, whereas there was an inverse relationship with the
      maintenance conditions of the sheds. In winter, rodent infestation was positively
      associated with the percentage of the borders of the farm covered with
      vegetation, and with the amount of plant cover, especially the amount of plant
      cover which was above 20 cm in height. 6. There was no significant relationship
      between rodent infestation and the time lag since the last application of
      rodenticide (first-generation anticoagulant) at the farms. 7. These results
      suggest that strategies for controlling rodents based solely on chemical methods
      may not be good enough for efficient rodent control. Farms which are properly
      managed, with a better control of vegetation growth at both the perimeter and
      within the internal area, in addition to a higher maintenance of sheds have
      appreciably lower rodent infestations.

PMID- 11469548
TI  - DMF effects on frozen gander semen.
AB  - 1. The objective of the present study was to determine if the age of semen donors
      affects the susceptibility of spermatozoa to freezing and whether DMF (dimethyl
      formamide) inseminated with freeze-thawed gander semen decreases fertility. 2.
      Semen was collected 3 times a week by dorsal-abdominal massage from two groups of
      White Italian ganders: 3 and 2 years-old. Both samples were diluted, mixed with
      DMF to a final concentration of 6% (v/v), pre-frozen and transferred into LN2. 3.
      Twice a week, the freeze-thawed semen was used for insemination of two groups of
      geese at a dose of 4 to 16 million live morphologically normal spermatozoa. One
      group was inseminated immediately after thawing, the 2nd with semen from which
      the DMF was removed. 4. Donor age had no effect on the spermatozoa's aptitude for
      freezing. The differences in quality and quantity of fresh and freeze-thawed
      semen produced by 3 or 2 year-old ganders were not significant. 5. The presence
      of DMF in the inseminated freeze-thawed semen did not affect the reproductive
      efficiency of spermatozoa. The fertility rate obtained with semen inseminated
      either with or without the cryoprotectant averaged 92.9% and 87.2% respectively.
      The hatchability of set eggs was 81.1% and 79.9% and, the hatchability of fertile
      eggs amounted to 87.3% and 89.4%.

PMID- 11469549
TI  - Development of components of the extracellular matrix, basal lamina and sarcomere
      in chick quadriceps and pectoralis muscles.
AB  - 1. The purpose of this study was to investigate differences in the development of
      components of the cell/matrix linkage in two functionally different muscle types:
      the pectoralis muscle, a major locomotory muscle in birds but not particularly
      functional in chickens, and the quadriceps muscle, a smaller and more
      functionally active muscle in the chicken. 2. The development of the
      extracellular matrix, basal lamina and sarcomere in the pectoralis and quadriceps
      muscles in chick embryos was examined biochemically to determine differences in
      the rate of development between these two muscles. Samples of these muscle types
      were dissected out from chick embryos from embryonic day 10 until 8 weeks post
      hatch. 3. Using SDS-PAGE electrophoresis and western blotting with antibodies
      against sarcomeric actin, laminin and collagens I, III and IV, it was apparent
      that muscle development begins earlier in the quadriceps muscle than in the
      pectoralis, and that late in the developmental process (d 18) both muscle types
      were well differentiated. The final concentration of collagens in the mature
      muscle remained higher in the quadriceps than in the pectoralis muscle. 4. The
      onset of development of the extracellular matrix, basal lamina and sarcomere was
      earlier in the quadriceps than the pectoralis, which could have functional
      implications for these muscles as a whole.

PMID- 11469550
TI  - Scanning electron microscopic observation of the architecture of collagen fibres
      in chicken M. iliotibialis lateralis.
AB  - 1. The collagen architecture of M. iliotibialis lateralis in chicken was observed
      under the scanning electron microscope after muscle maceration in NaOH. 2.
      Immunohistochemical methods showed Type I and III collagens to be distributed
      over both perimysium and endomysium. 3. Thick perimysium around secondary
      myofibre fasciculi was composed of many large longitudinal collagen bundles and a
      few small circumferential bundles. In contrast, thin perimysium around primary
      myofibre fasciculi showed mainly circumferential bundles. 4. Endomysium had a
      honeycomb-like structure and consisted of a fine collagen mesh, its main fibre
      striation being circumferential. 5. It is suggested that functional demand
      differs between thick perimysium and thin endomysium.

PMID- 11469551
TI  - Sexing on down and feather colour in the Dandarawi Egyptian breed.
AB  - 1. The study was on a population of the Egyptian local strain Dandarawi. Hatching
      records were obtained from three lines over two generations (1996 and 1997). Sex
      ratios were calculated using a total of 5,822 1-d-old chicks. 2. Sex could be
      identified at hatch by down colour. Female chicks showed a black spot on the head
      or irregular strips on the back, whereas males had no marks on head and back. At
      8 weeks of age, progeny could be easily sexed by feather colour, which was black
      and white for males and brown for females. The sexual dimorphism in feather
      colour at that age is due to the presence of the autosomal recessive wild type
      allele CO*N. Accuracy for autosexing at hatching time was 89-02% for males and 92
      42% for females. 3. Sex ratio deviated significantly from the expected value,
      1:1, in one line (line E) where the number of female chicks exceeded that of
      males, over the two generations. Chicks of both sexes exhibited the same survival
      rate up to 8 weeks of age.

PMID- 11469552
TI  - Genetic mapping of the QTL affecting body weight in chickens using a F2 family.
AB  - 1. To identify the quantitative trait loci (QTL) affecting growth in chickens, we
      carried out QTL analysis on chicken growth traits using a population of 227 F2
      crosses between a Satsumadori (slow-growing, light-weight Japanese native breed
      used as a meat chicken) male and a White Plymouth Rock (early-maturing, heavy
      weight broiler). 2. We chose 78 microsatellite loci from 331 publicly available
      on 14 linkage groups, with respect to their utility and location. 3. Two QTLs
      affecting body weight at 13 and 16 weeks were mapped at 220 cM on chromosome 1
      (LOD scores, 2.8 and 4.5, respectively, at 13 and 16 weeks), and at 60 cM on
      chromosome 2 (LOD scores, 6.2 and 8.1, respectively, at 13 and 16 weeks). 4. The
      closest loci to the QTLs were LEI71 on chromosome 1 and LMU13 and MCW184 on
      chromosome 2. 5. The sites of the QTLs agreed closely with those already
      reported. Therefore, it seems likely that QTLs affecting growth of chickens are
      located at these sites.

PMID- 11469553
TI  - Correlation between shell colour and ultrastructure in pheasant eggs.
AB  - 1. The histochemistry and ultrastructure of pheasant eggs were compared on the
      basis of blue or brown shell colour. 2. Differences in lectin histochemistry of
      the outer shell membrane calcification surface indicate a biochemical disruption
      of the calcification sites in blue eggs. 3. Significant differences were observed
      in all aspects of eggshell ultrastructure with blue eggs having thinner shells
      with structural defects. 4. Poor hatchability of blue eggs may reflect high rates
      of weight loss associated with a defective eggshell.

PMID- 11469554
TI  - Tenderisation of spent hen meat using ginger extract.
AB  - 1. The purpose of this work was to study the effect of ginger extract (GE) on
      tenderness of spent hen meat. 2. Spent hen meat chunks at either the pre- or post
      chilled stage were marinated with different concentrations (0%, 1%, 3% and 5%
      v/w) of GE and were evaluated after 24 h of treatment. 3. GE treatment increased
      the pH, moisture, cooking yield, total pigments, water holding capacity, collagen
      solubility, protein extractability, muscle fibre diameter and decreased the shear
      force values. 4. The electrophoretic pattern of muscle proteins revealed
      extensive proteolysis and reduction in number of protein bands in GE treated
      samples. 5. Tenderness scores were higher in samples treated at post-chilled
      stage. Of the different concentrations of GE examined, 3% was found optimum for
      tenderisation.

PMID- 11469555
TI  - Effect of genetic line, sex of birds and the type of bioassay on the
      metabolisable energy value of maize.
AB  - 1. Experiments were conducted to determine the differences in the energy
      utilisation of adult hens and cockerels of a layer (Rhode Island Red) and a
      broiler line (Cornish). The effect of 2 different precision-feeding methodologies
      (wet and dry-feeding) were also compared. Birds were fasted for 24 h, precision
      fed with 35 g dry or 33.5 g wet corn and fasted for a further 48 h period.
      Excreta were collected during this period. 2. Non of the parameters (method, sex,
      line) had a significant effect on the ME content of maize. However, a significant
      interaction was found between the sex of the birds and the methodology used.
      Females of both genetic lines utilised the energy content of maize more
      efficiently than males. The opposite was found when the wet precision-feeding
      method was used. 3. Weight loss and endogenous energy excretions (EEL) of birds
      were also effected by sex and genotype. Cockerels of both lines had significantly
      greater EEL than females. However, since hens lost less nitrogen, the nitrogen
      corrected EEL (EELn) was higher for the hens.

PMID- 11469556
TI  - Effect of oat hulls on performance, gut capacity and feed passage time in broiler
      chickens.
AB  - 1. Two experiments were conducted to study effects of oat hulls and their
      interaction with soluble fibre in broiler chickens. 2. In experiment 1, wheat or
      naked oats based diets with or without NSP-degrading enzymes were mixed with 0,
      40 or 100 g/kg oat hulls which replaced a maize starch/soy isolate mixture, and
      the diets were fed to broiler chickens from 7-21 d of age. 3. Production results,
      AMEn determined between 14 and 16 d of age, and ileal digestibility indicated no
      negative effect of oat hulls on nutrient digestibility or weight gain. 4. Feed
      consumption increased significantly when oat hulls were included in the diet and
      relative gut weight increased correspondingly (P<0.05). 5. No interaction effects
      were found between soluble and insoluble fibres, except for a possible effect on
      starch digestibility in wheat diets. 6. In experiment 2, mash diets were fed
      unsupplemented, or were supplemented with coarsely or finely ground oat hulls
      which replaced a maize starch/soy isolate mixture. 7. Faecal titanium dioxide
      excreted between 1 and 48 h after feeding of a gelatin capsule containing
      titanium dioxide, was used to calculate feed passage time. 8. There was a
      tendency (P=0.08) for faster feed passage with inclusion of coarsely ground oat
      hulls, but no effect of finely ground oat hulls was found.

PMID- 11469557
TI  - Effect of supplementary choline on the performance of broiler breeders fed on
      different energy sources.
AB  - 1. Laying performance, egg quality, fertility and hatchability, and fat
      deposition in liver and abdomen were recorded in broiler breeders (29 to 48 weeks
      of age) fed on diets containing perarl millet (Pennisetum typhoides) (PM), broken
      rice (BR) or yellow maize (YM) (600 g/kg diet). Constant ratios of metabolisable
      energy (ME) to other nutrients were maintained in all the diets. Food grade
      choline chloride (50%) was added to the diets at 3 concentrations (0, 760 and
      1,520 mg/kg). Each diet was offered to 3 replicate groups of 15 birds (12 hens
      and 3 cockerels), maintained in deep litter pens, to provide 1.46 MJ ME/bird/d.
      2. Neither the source of energy nor dietary choline content had any influence on
      hen-d egg production, fertility or hatchability. Food efficiency and egg weight
      were significantly reduced in BR-fed groups compared to those fed on the other
      energy sources. 3. The efficiency of energy and protein utilisation increased and
      liver fat content was decreased significantly by dietary choline supplementation.
      4. Haugh unit score, egg shell weight, liver weight and intestinal weight were
      not influenced by either supplementary choline or the source of energy. However,
      the yolk colour index was significantly reduced in PM- or BR-fed groups compared
      to those fed on the maize-based diet. 5. Deposition of abdominal fat was
      significantly greater in BR-fed birds compared to those fed on the YM-based diet,
      while liver fat content was significantly greater in the birds fed on the PM-or
      BR-based diets than those based on YM. Although supplementation of the diet with
      choline had no influence on abdominal fat deposition, liver fat content was
      significantly reduced in birds given diet containing 760 mg supplemental
      choline/kg diet. 6. The present study indicates that PM or BR can be used as
      principal energy sources in place of YM in broiler breeder diets without
      affecting egg production, fertility or hatchability. Liver fat content can be
      reduced by adding choline at 760 mg/kg to diets based on different energy
      sources.

PMID- 11469558
TI  - Effect of inclusion level of linseed on the nutrient utilisation of diets for
      growing broiler chickens.
AB  - 1. Diets containing linseed at inclusions of 0, 80, 120 and 160 g/kg were
      evaluated for digestibility of nutrients and AMEn content with male broiler
      chickens. 2. Increasing the concentration of linseed decreased the retention of
      nitrogen and the digestibility of amino acids, crude fat and fatty acids of
      diets. 3. Dietary AMEn (MJ/kg) was also affected by the rate of inclusion of
      linseed, values decreasing from 14.39 to 12.49. 4. In general, a linear
      regression model explained the relationship between dietary linseed content and
      nutritive parameters. However, the quadratic response found for the digestibility
      of several amino acids and fatty acids indicated a non-additive change in their
      digestibility. 5. Viscosity ofjejunal digesta was markedly increased by each
      increment of linseed in the diets. This is attributable to the presence of
      mucilage in linseed and it might explain many of the results obtained in this
      study.

PMID- 11469559
TI  - Utilisation of different phosphorus sources in relation to their fluorine content
      for broilers and layers.
AB  - 1. The relative utilisation of different phosphorus sources in relation to their
      fluorine (F) content was studied in commercial broilers (5 to 40 d) and White
      Leghorn layers (252 to 364 d). The phosphorus (P) sources tested were bonemeal
      (BM), low fluorine (LFRP) and high fluorine (HFRP) rock phosphates and a
      commercial mineral mixture (CMM). The P sources were incorporated in broiler and
      layer diets by replacing dicalcium phosphate (DCP) on a P basis. 2. The F
      contents of diets based on BM, LFRP, CMM and HFRP were 53, 365, 622 and 1383
      mg/kg in the broiler experiment and 34, 242, 437 and 967 mg/kg in the layer
      experiment, respectively. F was not detected in DCP based diets. 3. In broilers,
      body weight gain, food intake, gain: food, P retention and serum inorganic P
      content on P sources (BM and LFRP) containing F up to 365 mg/kg diet were similar
      to those on DCP. Body weight gain, food intake, serum calcium and inorganic P
      contents and retention of P were depressed in groups fed on CMM and HFRP, which
      may have been due to the toxic effects of F (622 and 1383 mg/kg) present in diets
      based on these P sources. 4. Bone ash and its P content were not affected by
      feeding diets containing F up to 1383 mg/kg from various P sources. The amount of
      F deposited in tibia increased significantly with increases in dietary F
      concentration. 5. In layers, egg production and food intake were not affected by
      F up to 437 mg/kg in diets containing BM, LFRP or CMM as the sole source of
      supplemental P. Egg production and food intake were depressed significantly in
      layers given the diet containing 967 mg F/kg from HFRP. 6. Egg mass: food, egg
      weight, shell quality (shell thickness and shell weight) and serum calcium and
      inorganic P levels were not affected by F up to 967 mg/kg in diets containing
      different P sources. 7. It may be concluded that the performance of broilers and
      layers was not affected by feeding various P supplements with dietary levels of F
      up to 365 and 437 mg/kg, respectively. The reduced performance in broilers and
      layers observed with some of the P sources may have been due to poor availability
      of P and/or toxic effects of F (622 and 967 mg/kg, respectively).

PMID- 11469560
TI  - Cryopreservation of gander semen.
AB  - 1. The effect of dimethylacetamide (DMA) and dimethyl sulphoxide (DMSO) on the
      cryopreservation of gander semen were investigated. An improved survival rate of
      spermatozoa after freeze-thawing was obtained when semen was frozen by a fast
      freezing procedure on dry ice with 9% DMA as the cryoprotectant. 2. Gander semen,
      which was frozen during mid season, was tested for fertilising ability in
      different times of the season. The percentage of fertility during d 3 to d 9
      after 2 consecutive inseminations was 68% to 95%, depending on the date of
      artificial insemination.

PMID- 11469561
TI  - Development of disaccharidase activity in the small intestine of broiler
      chickens.
AB  - 1. The changes in disaccharidase activity in the small intestine of broiler
      chickens were investigated in isolated enterocytes on d 18 of embryonic
      development and d 1, 7, 21, 35 and 56 after hatching. 2. The specific activities
      of maltase, lactase and trehalase were greatest on d 18 of embryonic development.
      After hatching, maltase specific activity gradually decreased until d 18. 3.
      After d 7 postnatally only traces of lactase and trehalase activity were found in
      the enterocytes. 4. Significant sucrase activity was found on d 18 of embryonic
      development and the activity of this enzyme increased 2-fold after hatch and
      remained generally constant up to d 35, after which the enzyme specific activity
      declined.

PMID- 11469562
TI  - Changes in chicken egg white cystatin concentration and isoforms during
      embryogenesis.
AB  - 1. A higher concentration of cystatin, measured using the ELISA technique, was
      found in whites from unfertilised than fertilised eggs. 2. Up to day 8 of
      embryogenesis a decrease in cystatin concentration was observed, then at d 10 the
      concentration rose reaching the maximal value at d 14. 3. Immunoblot analyses
      showed both phosphorylated and nonphosphorylated isoforms of chicken cystatin in
      unfertilised egg white as well as in egg yolk and chicken serum. 4. Significantly
      lower immunostaining of the phosphorylated form after the 4th d of embryogenesis
      in egg white suggests its preferential transport into the yolk sac.

PMID- 11469563
TI  - Effects of chromium nicotinate on performance, carcase characteristics and blood
      chemistry of growing turkeys.
AB  - 1. The objective of this trial was to study the effects of chromium nicotinate
      (Cr) supplementation on the performance, carcase characteristics and blood
      constituents of 9 to 22 week-old male turkeys. 2. Fifty-four 8-week-old male
      turkeys weighing 2.9 +/- 0.28 kg were allocated at random into 9 groups with 3
      dietary treatments and 3 replicates. The dietary treatment was different dietary
      concentrations of chromium in the basal diet, to provide 0 (control), 1 or 3
      mg/kg. The feeding trial lasted for 14 weeks. 3. Results showed that 1 mg/kg
      chromium supplementation significantly improved weight gain and food intake at 9
      to 18 weeks of age but did not significantly influence performance at 19 to 22
      week of age. The breast and thigh muscle were significantly increased in birds
      receiving 1 mg/kg chromium supplementation but were decreased by 3 mg/kg of
      supplementation. 4. Dietary chromium supplementation did not significantly
      influence other serum constituents, including insulin, HDL, VLDL+LDL, HDL-C, VLDL
      C+LDL-C, total protein, albumin, and gamma-globulin at 18 and 22 weeks of age. 5.
      The serum triacylglycerol (TG) and uric acid contents were significantly
      increased, while glycerol and alpha-globulin were significantly reduced by 3
      mg/kg chromium supplementation. However, 1 mg/kg chromium supplementation
      significantly reduced serum cholesterol and glycerol at 18-weeks old. At 22 weeks
      of age, 1 mg/kg chromium supplementation significantly increased serum glucose
      and decreased the uric acid concentration whereas 3 mg/kg chromium
      supplementation significantly increased the creatinine concentration and
      decreased beta-globulin concentration.

PMID- 11469564
TI  - Influence of ketone body and the inhibition of fatty acid oxidation on the food
      intake of the chick.
AB  - 1. Fatty acid oxidation is known to be involved in the control of food intake in
      mammals. The effect of fatty acid oxidation on food intake in chickens was
      studied using a ketone body (beta-hydroxybutyrate (beta-HB)) and mercaptoacetate
      (MA) (an inhibitor of fatty acid oxidation). 2. Central and peripheral injection
      of beta-HB decreased food intake in a dose-dependent manner, while low doses of
      MA had no effect. Higher doses of MA inhibited feeding but also caused mortality.
      3. These results indicate that ketone bodies act as an inhibitory signal for food
      intake in both the central and peripheral nervous systems but that inhibition of
      fatty acid oxidation may not be associated with feeding behaviour in chicks.

PMID- 11469565
TI  - Corporate, trade issues unfold at Chile summit.

PMID- 11469566
TI  - How to control a 'virtual outbreak'.

PMID- 11469567
TI  - Pet food manufacturer comments on testing of raw food diets.

PMID- 11469568
TI  - Questions interaction of sex and age on risk of lower urinary tract disease in
      cats.

PMID- 11469569
TI  - Disappointed reader honest with editor.

PMID- 11469570
TI  - Veterinary practice management education in the Association of American
      Veterinary Medical Colleges member colleges during 1999.
AB  - Most veterinary students enrolled at AAVMC member institutions take at least 1
      VPM course prior to graduation. These courses are characterized by widespread
      involvement of outside lecturers with business expertise, which likely adds to
      their strength. However, it remains that wide variation in VPM education exists
      across the AAVMC with regard to the topics addressed, the specific business
      expertise of faculty and administrative course specifics. As such, the situation
      provides several key opportunities. Foremost among these is the immediate need
      for profession-wide discourse on VPM education to define reasonable expectations
      with regard to the business skills of veterinary graduates. In addition, outcomes
      assessment would provide information on which of the widely varying approaches to
      VPM education is most likely to produce successful graduates. The opportunity
      also exists for development of academic research programs to support VPM
      education directly by strengthening the related disciplinary knowledge base.
      Effective leadership for these efforts will be crucial to their success.

PMID- 11469571
TI  - What is your diagnosis? Segmental dilatation of the small intestine with intra
      intestinal fluid and air indicative of small-intestinal obstruction.

PMID- 11469572
TI  - Efficacy of an amitraz-impregnated collar in preventing transmission of Borrelia
      burgdorferi by adult Ixodes scapularis to dogs.
AB  - OBJECTIVE: To determine whether an amitraz-impregnated collar could prevent
      transmission of Borrelia burgdorferi by Ixodes scapularis to dogs. DESIGN:
      Laboratory trial. ANIMALS: 8 specific-pathogen-free Beagles. PROCEDURE: On days 
      15 and -1, all dogs had negative ELISA results for serum antibodies against B.
      burgdorferi. On day 0, 4 dogs were each fitted with an amitraz-impregnated (9%)
      collar, and 4 dogs served as untreated controls. On day 7, all dogs were infested
      with 100/scapularis (approx 50 females and 50 males) with a known B. burgdorferi
      infectivity rate of 39.4%. On days 21, 28, 35, 42, 56, 70, and 84, each dog was
      tested for serum antibodies against B. burgdorferi via ELISA and a western blot
      technique. Additional ELISA were also performed for serum antibodies against
      antigenically similar organisms. RESULTS: By day 70, all control dogs had
      developed serum ELISA responses ranging from 328 to 510 kinetics-ELISA units
      (equivalent to end-point titers of approx 43,500 to 60,000), whereas treated dogs
      remained seronegative throughout the study. Western blot assays performed on all
      serum samples confirmed that antibodies detected in control dogs reflected
      responses to specific antigens of B. burgdorferi, whereas treated dogs had no
      such antibodies. Additional serologic analyses confirmed that antibody responses
      observed in control dogs were not attributable to antigenically similar
      organisms. CONCLUSIONS AND CLINICAL RELEVANCE: Amitraz-impregnated collars
      prevented transmission of B. burgdorferi in 4 of 4 treated dogs and may be a
      useful management tool for prevention of borreliosis in dogs.

PMID- 11469573
TI  - Functional cystic thyroid adenoma in a cat.
AB  - A 9-year-old cat with hyperthyroidism was referred for radioactive iodine
      treatment. The cat also had a ventral cervical mass that the owners reported had
      been present for several years and had increased in size during the past few
      weeks. On physical examination, the mass was found to have caused lateral
      displacement of the trachea, esophagus, jugular vein, and common carotid artery.
      The mass was aspirated and was determined to be cystic in nature. Concentrations
      of thyroid hormones in the cystic fluid were similar to serum concentrations, and
      nuclear scintigraphy revealed thyroactive tissue lining the cyst wall. Magnetic
      resonance imaging suggested that the cyst originated from the right lobe of the
      thyroid gland. The cat was treated with sodium iodide I 131 but died 4 days
      later, presumably as a result of aspiration of gastric or esophageal contents. A
      necropsy was not performed, but histologic examination of a biopsy specimen of
      the mass indicated that it was a cystic thyroid adenoma.

PMID- 11469574
TI  - Macracanthorhynchus ingens infection in a dog.
AB  - A 4-month-old sexually intact female Siberian Husky was examined because of
      diarrhea and 4 flesh-colored annulated helminths that were recovered from the
      dog's feces. Infection with Macracanthorhynchus ingens was diagnosed on the basis
      of morphologic features of the adult parasites and ova. Spindle-shaped eggs (mean
      length, 91 microm; mean width; 54 microm) were obtained from the body cavity of a
      gravid female specimen. The dog was treated empirically with epsiprantel (5.5
      mg/kg [2.5 mg/lb] of body weight) and ivermectin (250 to 500 microg/kg [114 to
      227 microg/lb]), and the diarrhea resolved. Infection with this parasite has been
      reported in raccoons from the same geographic area. Macracanthorhynchus ingens is
      typically a parasite of raccoons, wolves, badgers, foxes, skunks, mink, and
      moles; transmission from wildlife to dogs may occur via ingestion of infected
      intermediate hosts (millipedes).

PMID- 11469575
TI  - Clinical, clinicopathologic, radiographic, and ultrasonographic characteristics
      of intestinal lymphangiectasia in dogs: 17 cases (1996-1998).
AB  - OBJECTIVE: To characterize the clinical, clinicopathologic, and imaging findings
      in dogs with intestinal lymphangiectasia and to compare the histologic grade of
      lymphangiectasia with clinicopathologic and imaging abnormalities. DESIGN:
      Retrospective study. ANIMALS: 17 dogs with a histologic diagnosis of intestinal
      lymphangiectasia. PROCEDURE: Medical records of dogs with a histologic diagnosis
      of intestinal lymphangiectasia were reviewed for signalment, history, clinical
      signs, results of exploratory laparotomy, and clinicopathologic, radiographic,
      ultrasonographic, and histologic findings. RESULTS: Mean age of dogs was 8.3
      years; the most common clinical signs were diarrhea, anorexia, lethargy,
      vomiting, and weight loss. Abnormal physical examination findings included
      dehydration, ascites, and signs of pain on palpation of the abdomen. The most
      notable clinicopathologic findings were low serum ionized calcium concentration
      and hypoalbuminemia. Abdominal ultrasonography was performed in 12 dogs and
      revealed intestinal abnormalities in 8 dogs and peritoneal effusion in 7 dogs.
      Exploratory laparotomy revealed abnormalities in 9 of 16 dogs including thickened
      small intestine, dilated lacteals, lymphadenopathy, and adhesions. On histologic
      examination of the small intestine, concurrent inflammation was observed in 15 of
      17 dogs, crypt ectasia in 5 of 17, and lipogranulomas in 2 of 17. CONCLUSIONS AND
      CLINICAL RELEVANCE: Intestinal lymphangiectasia in dogs appears to be a
      heterogeneous disorder characterized by various degrees of panhypoproteinemia,
      hypocholesterolemia, lymphocytopenia, and imaging abnormalities. In most dogs,
      the severity of hypoalbuminemia appears to offer the best correlation with
      severity of histologic lesions of lymphangiectasia. Imaging abnormalities are
      common in dogs with intestinal lymphangiectasia but are not specific enough to
      differentiate this disorder from other gastrointestinal disorders, nor are they
      predictive of histologic severity.

PMID- 11469576
TI  - Dermatologic disorders in dogs with diabetes mellitus: 45 cases (1986-2000).
AB  - OBJECTIVE: To characterize skin lesions and causative infections in diabetic dogs
      and evaluate other potential causes of dermatologic disorders, including
      concurrent endocrinopathies, allergic skin disease, and long-term corticosteroid
      administration. DESIGN: Retrospective study. ANIMALS: 45 dogs with diabetes
      mellitus (DM) that were examined by dermatologists. PROCEDURE: Medical records
      were reviewed for signalment; allergic conditions prior to development of DM;
      prior corticosteroid administration; and results of dermatologic examinations,
      ear and skin cytologic examinations, skin scrapings for parasites, bacteriologic
      and fungal culturing of ear and skin specimens, histologic examinations, and
      endocrine testing. RESULTS: Bacterial skin infection was the most common
      dermatologic disorder (n = 38 [84%]), followed by otitis (26 [58%]) and
      Malassezia-induced dermatitis (19 [42%]). Twenty-two (49%) dogs had pruritic skin
      disease consistent with allergic dermatitis, which preceded diagnosis of DM.
      Prior corticosteroid administration was reported in 21 (47%) dogs. Concurrent
      hyperadrenocorticism was diagnosed in 13 (29%) dogs, and concurrent
      hypothyroidism was diagnosed in 5 (11%) dogs. Iatrogenic hyperadrenocorticism was
      diagnosed in 1 additional dog. Only 10 (22%) dogs did not have a documented
      concurrent endocrinopathy or allergic disease that could have caused the
      dermatitis. CONCLUSIONS AND CLINICAL RELEVANCE: Bacterial and yeast-induced
      dermatitis and otitis develop in dogs with DM. Many diabetic dogs with
      dermatologic problems have a preexisting allergic condition, history of prior
      corticosteroid administration, or concurrent endocrinopathy that may be a more
      likely cause of dermatologic problems than DM alone.

PMID- 11469577
TI  - Causes of death or reasons for euthanasia in military working dogs: 927 cases
      (1993-1996).
AB  - OBJECTIVE: To determine causes of death or reasons for euthanasia in a population
      of military working dogs. DESIGN: Retrospective study. ANIMALS: 927 military
      working dogs. PROCEDURE: Records of all military working dogs that died during
      the period from 1993 to 1996 were evaluated for cause of death or reason for
      euthanasia by review of necropsy and histopathology reports, death certificates,
      and daily clinical treatment sheets. A single primary cause of death or
      euthanasia was determined. RESULTS: Although sexually intact male dogs were more
      numerous in the study population, castrated male dogs typically lived longer than
      spayed females or sexually intact males. Leading causes of death or euthanasia
      (76.3% of all dogs) were appendicular degenerative joint disease, neoplasia,
      spinal cord disease, nonspecific geriatric decline, and gastric dilatation
      volvulus. Compared with German Shepherd Dogs, Belgian Shepherd Dogs were at
      increased risk for death attributable to neoplasia, behavior, and respiratory
      tract disease. German Shepherd Dogs had nearly twice the risk for death
      associated with spinal cord diseases, compared with Belgian Shepherd Dogs.
      CONCLUSIONS AND CLINICAL RELEVANCE: For most military working dogs, death or
      euthanasia results from a few diseases commonly associated with advanced age.
      Some breed differences in risk for these diseases may exist, which clinicians
      should consider in the procurement and long-term management of these dogs.

PMID- 11469578
TI  - Injury to the origin of the gastrocnemius muscle as a possible cause of lameness
      in four horses.
AB  - Four horses were evaluated because of hind limb lameness. Two had a distinct gait
      abnormality at the walk characterized by lateral rotation of the point of the
      calcaneus and medial rotation of the toe during the stance phase. Nuclear
      scintigraphy revealed a focal area of intense radioisotope uptake in the
      caudodistal aspect of the femur in all 4 horses, and 3 of the horses had a
      corresponding proliferative reaction on the caudodistal cortex of the femur on
      radiographs. In all 4 horses, a diagnosis of injury to the origin of the
      gastrocnemius muscle was made. Three of the horses returned to athletic endeavors
      after an extended period of rest and a gradual return to exercise. The fourth
      improved after 5 months of rest but became lame again when returned to exercise
      and was euthanatized.

PMID- 11469579
TI  - Reproductive effects of estradiol cypionate in postparturient dairy cows.
AB  - OBJECTIVE: To determine the effects of estradiol cypionate (ECP) on measures of
      reproductive efficiency in postparturient dairy cows. DESIGN: Randomized clinical
      trial. ANIMALS: 273 cows in a single herd in California. PROCEDURE: Twenty-four
      hours after parturition, 122 cows were treated with ECP (4 mg, IM); the remaining
      151 cows were untreated controls. Percentages of cattle with abnormal findings
      during uterine palpation 27 to 40 days after parturition were compared between
      groups, along with days to first artificial insemination (AI), percentages of
      cows that were not pregnant after the first AI, and days to pregnancy. RESULTS:
      Treatment with ECP did not have a significant effect on whether results of
      uterine palpation 27 to 40 days after parturition were abnormal, days to first
      AI, or odds that a cow would be pregnant after the first AI. Treatment with ECP
      appeared to have a negative effect on days to pregnancy (hazard ratio, 0.72)
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that prophylactic
      administration of ECP during the early postparturient period in dairy cows did
      not have measurable beneficial effects on reproductive efficiency.

PMID- 11469580
TI  - Glycosyltransferases in secondary plant metabolism: tranquilizers and stimulant
      controllers.
AB  - Plants are exposed to a wide range of toxic and bioactive low-molecular-weight
      molecules from both exogenous and endogenous sources. Glycosylation is one of the
      primary sedative mechanisms that plants utilise in order to maintain metabolic
      homeostasis. Recently, a range of glycosyltransferases has been characterized in
      detail with regard to substrate specificity. The next step in increasing our
      understanding of the biology of glycosylation will require information regarding
      the exact role of individual glycosyltransferases in planta, as well as an
      insight into their potential involvement in metabolon-complexes. Hopefully, this
      will answer how a large number of glycosyltransferases with broad, rather than
      narrow, substrate specificity can be constrained in order to avoid interfering
      with other pathways of primary and secondary metabolism. These and other topics
      are discussed.

PMID- 11469581
TI  - Constancy of nitrogen turnover kinetics in the plant cell: insights into the
      integration of subcellular N fluxes.
AB  - Compartmental analysis with 13N was used to determine cytosolic nitrate (NO3-)
      pools, and their turnover rates, in roots of intact barley (Hordeum vulgare L. cv
      Klondike) seedlings. Influx, efflux, flux to the vacuole and assimilation, and
      flux to the xylem, varied as much as 300-fold over a wide range of external NO3-
      conditions. By contrast, the kinetic constant kc describing cytosolic NO3-
      turnover varied by less than 4% from a mean value of 0.0407 min(-1). Accordingly,
      cytosolic NO3- pools varied linearly with influx. A literature survey showed that
      kc constancy is observed with both NO3- and ammonium (NH4+) fluxes in many plant
      species, including H. vulgare, Arabidopsis thaliana, Picea glauca, and Oryza
      sativa. The regulatory system implied by this phenomenon is fundamentally
      different from that of potassium (K+) fluxes, in which cytosolic pool size is
      held constant while kc varies with external K+ concentrations. We further present
      data showing that barley plants, grown on one steady-state concentration of NH4+,
      restore kc within minutes of exposure to new, non-steady-state, NH4+
      concentrations. We propose the existence of a high-fidelity mechanism governing
      the timing of cytosolic N turnover, and discuss its implications for attempts to
      improve plants biotechnologically.

PMID- 11469582
TI  - Immunocytochemical localization of esterified and unesterified pectins in
      unpollinated and pollinated styles of Petunia hybrida Hort.
AB  - Localization of pectins in the style of Petunia hybrida before and after
      pollination was investigated by immunocytochemistry using two primary monoclonal
      antibodies specific to highly (JIM7) and weakly (JIM5) methylesterified pectins.
      In the unpollinated style, esterified pectins occurred mainly in the cell walls
      of cortex tissue, while unesterified pectins were present mainly in the
      extracellular matrix (ECM) of the transmitting tract. After pollination no
      remarkable differences were found in pectin distribution in the ground tissue of
      the style. On the other hand, in the transmitting tract a reduction in the
      quantity of unesterified pectins was observed. Unesterified pectins in the
      extracellular regions of the transmitting tissue decreased before the penetration
      of the pollen tubes, indicating that pollination induces a reduction in the
      amount of unesterified pectins in the transmitting-tract ECM. The correlation
      between the degradation of strongly Ca2+-binding pectins and the growing level of
      those ions in the extracellular regions of the transmitting tract in the
      pollinated pistil of P. hybrida (M. Lenartowska et al. 1997) suggests that this
      process may constitute a mechanism for creating an optimum calcium medium for in
      vivo-growing pollen tubes. Both pectin categories were localized in pollen tubes.
      Esterified pectin epitopes were localized mainly in the vesicles of the tip
      cytoplasm. Unesterified pectin epitopes were found in the external fibrillar wall
      of pollen tubes.

PMID- 11469583
TI  - Temporal and spatial patterns of twining force and lignification in stems of
      Ipomoea purpurea.
AB  - Using the TWIFOR, an electronic device for continuous, in vivo measurement of the
      forces exerted by twining vines, we examined the forces generated by vines
      growing on cylindrical poles of slender (6.35 mm) and thicker (19.05 mm)
      diameter. In stems of Ipomoea purpurea (L.) Roth. magnitudes of twining force
      (axial tensions) were, on average, less at a particular time and location on the
      more slender poles; while twining loads (normal force per unit length of vine)
      were much greater on the slender poles because of the greater curvature of the
      vines. Thus, the geometry of the helix formed by the vine on the pole affects the
      ability of the vine to maintain a frictional interaction with its support. In
      addition, the plant-to-plant variation in twining force was twice as great on the
      thicker support poles. Metaxylem and fibers developed closer to the plant apex in
      vines on the slender poles. On the thicker poles, a significant fraction of the
      maximum twining force developed during the establishment of the first gyre,
      before fibers were lignified, indicating that primary growth can be sufficient to
      establish high twining forces. On the slender poles, however, twining force
      increased with developmental stage until the gyre was at least 1.5 m from the
      apex. Thus, twining force can increase after cessation of primary growth. No
      simple relationship was found between the site of fiber differentiation and
      twining force.

PMID- 11469584
TI  - Isolation and characterization of an endonuclease synthesized by barley (Hordeum
      vulgare L.) uninucleate microspores.
AB  - Few biochemical and molecular details are available on microspore growth and
      development. In this work, a nuclease was partially purified from diffusates of
      barley (Hordeum vulgare L.) microspores by using concanavalin-A as ligand. The
      chromatographic preparation contained a 34-kDa protein with nucleolytic activity;
      the enzyme (called BMN: barley microspore nuclease) was very stable at pH > 8.0
      and temperatures below 50 degrees C. Activity was highest at pH 5.6 and increased
      almost exponentially with temperature until a breakpoint between activity and
      stability was reached at 70 degrees C. Although BMN was able to cleave RNA, the
      enzyme showed a remarkable preference for DNA, especially in the single-stranded
      form. The best homopolymeric substrates were poly(dA) and poly(A), whereas
      poly(dC), poly(G) and poly(I) were almost completely uncleaved. When incubated
      with intact nuclei, BMN caused a nucleosomal DNA ladder of approximately 200 bp.
      On the basis of DNA laddering, substrate specificity, Mg2+ -dependence and best
      performance at apoplastic pH, BMN can be referred to as a putative apoptotic
      nuclease involved in pollen development.

PMID- 11469585
TI  - Microautoradiographic localisation of a glucosinolate precursor to specific cells
      in Brassica napus L. embryos indicates a separate transport pathway into myrosin
      cells.
AB  - The in-situ localisation of a desulpho-glucosinolate precursor has been studied
      by microautoradiography of cryo-sections from immature seeds and pods of the high
      glucosinolate Brassica napus L. cv. Argentine collected 23 days after
      pollination. After feeding with the tritium-labelled glucosinolate precursor [4,5
      3H](beta-D-glucopyranosyl)-4-pentenethiohydroxamic acid, embryo radicles,
      cotyledons and pod-wall were frozen in liquid nitrogen. Cryotome sections were
      freeze-dried and coated with nuclear emulsion autoradiographic film. A distinct
      pattern of radioactivity derived from the glucosinolate precursor was found in
      specific cells in both radicle and cotyledons. In contrast, the labelling in pod
      walls was not cell specific, but general at the inner side of the pod wall. The
      results show that the glucosinolate/desulphoglucosinolate was localised in
      specific cells, in a pattern resembling that of myrosin cells known to contain
      myrosinase (EC 3.2.3.1). In addition [4,5-3H](beta-D-glucopyranosyl)-4
      pentenethiohydroxamic acid was fed to immature seeds and pods of B. napus and a
      quantitative incorporation into 2-hydroxy-3-butenylglucosinolate and 3-butenyl
      glucosinolate was observed. When [4,5-3H](beta-D-glucopyranosyl)-4
      pentenethiohydroxamic acid was fed to 4-day-old seedlings the label was taken up
      by all tissues. We propose a model in which glucosinolate/desulphoglucosinolates
      are transported to myrosin cells to participate in the myrosinase-glucosinolate
      multifunctional defence system.

PMID- 11469586
TI  - The lipopolysaccharides of the phytopathogen Xanthomonas campestris pv.
      campestris induce an oxidative burst reaction in cell cultures of Nicotiana
      tabacum.
AB  - The lipopolysaccharides (LPSXcc) of the phytopathogenic bacteria Xanthomonas
      campestris pv. campestris (X.c.c.) were purified from an exopolysaccharide
      deficient mutant strain. The isolated LPSxcc induced an oxidative burst reaction
      in cell-suspension cultures of the non-host plant tobacco (Nicotiana tabacum L.)
      SRI. The oxidative burst elicited by LPSXcc differed from that induced by yeast
      elicitor (YE), a cell wall preparation of baker's yeast. The LPSXcc-induced
      oxidative burst was characterised by a slow increase in H2O2 production and an
      extended decline. Both the LPSXcc-and YE-induced oxidative bursts were completely
      blocked by the NAD(P)H-oxidase inhibitor diphenylene-iodonium. When LPSXcc and YE
      were applied in combination, a synergistic effect and the establishment of
      refractory states in the generation of H2O2 were observed. The amount of
      cytosolic calcium was measured in transgenic tobacco cell cultures carrying the
      apoaequorin gene by coelenterazine-derived chemiluminescence. Whereas YE induced
      a calcium peak within 1 min after application, LPSXcc induced a long-term calcium
      signal without transients. To our knowledge this is the first report on the
      elicitation of an oxidative burst in plant cell cultures by isolated LPS of a
      phytopathogenic bacterium.

PMID- 11469587
TI  - A putative plant homolog of the yeast beta-1,3-glucan synthase subunit FKS1 from
      cotton (Gossypium hirsutum L.) fibers.
AB  - A novel plant gene CFL1 was cloned from cotton (Gossypium hirsutum L.) fibers by
      expressed sequence tag (EST) database searching and 5'-RACE (rapid amplification
      of cDNA ends). This gene shows sequence homology with FKS1 which has been
      identified as the putative catalytic subunit of the yeast beta-1,3-glucan
      synthase. It encodes a protein (CFL1p) of 219 kDa with 13 deduced transmembrane
      helices and 2 large hydrophilic domains, one of which is at the N-terminus and
      the other in the internal region of the polypeptide. CFL1 displays 21% identity
      and 41% similarity to FKS1 at the amino acid level over its entire length, with
      31% identity and 52% similarity for the hydrophilic central domain. Using RNA and
      protein blot analysis, CFL1 was found to be expressed at higher levels in cotton
      fibers during primary wall development. CFL1 also had a strong expression in
      young roots. Using a calmodulin (CaM)-gel overlay assay, the hydrophilic N
      terminal domain of CFL1p was shown to bind to CaM, while the hydrophilic central
      domain did not. A putative CaM-binding domain, 16 amino acids long, was predicted
      in the hydrophilic N-terminal domain. Moreover, a product-entrapment assay
      demonstrated that a protein associated with an in vitro-synthesized callose
      pellet could be labeled by anti-CFL1 antibodies. Our finding suggests that CFL1
      is a putative plant homolog of the yeast beta-1,3-glucan synthase subunit FKS1
      and could be involved in callose synthesis.

PMID- 11469588
TI  - A xylosyltransferase that synthesizes beta-(1-->4)-xylans in wheat (Triticum
      aestivum L.) seedlings.
AB  - A particulate preparation from 6-day-old seedlings of wheat (Triticum aestivum
      L.) was found to contain a xylosyltransferase (XylTase) which incorporated xylose
      (Xyl) from UDP-xylose into exogenous beta-(1-->4)-xylooligosaccharides with 2
      aminopyridine-derivatized reducing end groups. High-performance liquid
      chromatographic analysis showed that the chain elongation of pyridylaminated beta
      (1-->4)-xylotriose (Xyl3-PA) occurred by attachment of a series of one, two, or
      three xylosyl residues, depending on substrate concentrations and reaction times.
      Methylation analysis and beta-xylosidase digestion of the newly synthesized Xyl4
      PA confirmed that the xylosyl residues were incorporated through beta-(1-->4)
      linkages. The enzyme was maximally active at pH 6.8 and 20 degrees C, and
      required Triton X-100, which enhanced activity 5-fold at a concentration of 0.05
      2%. Divalent ions, including Mn2+ and Mg2+, did not affect activity. Enzyme
      activity increased with increasing polymerization of xylosyl residues of the
      acceptor substrates: for instance, Xyl5-PA was almost 7 times as efficient as
      Xyl2-PA. The apparent Michaelis constants of the enzyme for Xyl3-PA and UDP
      xylose were 13.5 and 7.9 mM, respectively. The enzyme also catalyzed
      incorporation of radioactive sugars (Xyl together with a small portion of L
      arabinose) from UDP-[14C]xylose into higher beta-(1-->4)-xylooligosaccharides
      (degree of polymerization > 7) with or without (4-O-methyl-)glucuronosyl side
      chains at activities comparable to those observed for pyridylaminated
      xylooligosaccharides, and into several heteroxylans but with much lower
      efficiency. Enzymatic hydrolysis of the product with a beta-xylanase degraded it
      into mainly xylobiose, providing further evidence that the xylosyl residues are
      incorporated through beta-(1-->4)-linkages.

PMID- 11469589
TI  - The nitrogen content of the tomato leaf apoplast increases during infection by
      Cladosporium fulvum.
AB  - To address the problem of the nutritional requirements of phyto-pathogenic fungi
      growing in planta, the environment for the intercellular biotrophic pathogen,
      Cladosporium fulvum Cooke, of tomato (Lycopersicon esculentum Mill.) was
      analysed. Using a novel technique for infiltrating the intercellular space, we
      measured the concentrations of 21 amino acids, nitrate and ammonia in the
      apoplast of the tomato leaf during infection. The concentrations of most amino
      acids, and total nitrogen content, increased during infection. The levels of
      nearly all amino acids remained relatively unchanged during an incompatible
      interaction. All protein amino acids were detected during infection, except
      cysteine and tryptophan. Most amino acids were present at a concentration between
      0.1-0.7 mM. The non-protein amino acid gamma-aminobutyric acid was detected at
      the highest concentration (up to 2.5 mM) during the compatible interaction.
      Preliminary investigations on the source of the amino acids revealed that
      protease activity within the apoplast increased during infection and that
      infection induced the expression of the pathogenicity-related extracellular
      serine protease P69B. The nitrogen status of the infecting fungus and sources for
      the additional amino acids are discussed.

PMID- 11469590
TI  - Partial purification and characterization of a protein inhibitor of
      phosphoenolpyruvate carboxylase kinase.
AB  - The activity of phosphoenolpyruvate carboxylase (PEPCase) kinase in leaf extracts
      increased markedly on dilution. This was shown to be caused by the presence of a
      protein that inhibits the kinase. The inhibitor protein was separated from the
      kinase and purified partially. It inhibited the kinase reversibly, presumably by
      a direct interaction; it was neither a protease nor a protein phosphatase. The
      amounts of kinase and inhibitor in leaves were estimated following separation by
      hydrophobic chromatography. The amount of inhibitor in the crassulacean acid
      metabolism plant Kalanchoe fedtschenkoi Hamet et Perrier was sufficient to
      inhibit the basal level of kinase activity present during the light period and
      the early stages of the dark period. Similarly, the amount of inhibitor in the C4
      plant Zea mays L. was sufficient to inhibit the low amount of kinase activity
      present in the dark and at moderate light intensity. Analogous to the role of the
      protein inhibitor of mammalian cyclic AMP-dependent protein kinase, the function
      of the PEPCase kinase inhibitor may be to inhibit the basal level of kinase
      present in conditions under which rapid flux through PEPCase is not required.

PMID- 11469591
TI  - Copy-DNA cloning and characterisation of a potato alpha-glucosidase: expression
      in Escherichia coli and effects of down-regulation in transgenic potato.
AB  - Polymerase chain reaction-based methodology was used to obtain a cDNA clone
      (MAL2) from potato (Solanum tuberosum L.) with the sequence characteristics of an
      alpha-glucosidase. Phylogenetic analysis of the deduced polypeptide encoded by
      this cDNA demonstrated that the most similar sequences were alpha-glucosidases
      and alpha-xylosidases of plant origin. The MAL2 cDNA was expressed in Escherichia
      coli and the recombinant MAL2 protein was affinity-purified. MAL2 catalysed the
      hydrolysis of a range of maltooligomers and p-nitrophenyl-alpha-D-glucopyranoside
      with a pH optimum of 5.5-5.7. The substrate with the lowest Km value was
      maltotetraose (3.7 mM). The MAL2 expression product did not catalyse the
      hydrolysis of xyloglucan oligosaccharides, p-nitrophenyl-alpha-D-xylopyranoside
      or gelatinised potato starch. MAL2 was down-regulated in transgenic potato plants
      using an antisense approach. In several independent transgenic antisense lines,
      MAL2 expression was severely down-regulated. Despite this, no decrease in total
      extractable alpha-glucosidase and alpha-xylosidase activity could be detected in
      tissues from the transgenic plants. In glasshouse trials, no visible phenotype,
      change in tuber yield or carbohydrate content was associated with MAL2 down
      regulation. The implications of these results are discussed.

PMID- 11469592
TI  - Glutamine and alpha-ketoglutarate are metabolite signals involved in nitrate
      reductase gene transcription in untransformed and transformed tobacco plants
      deficient in ferredoxin-glutamine-alpha-ketoglutarate aminotransferase.
AB  - Transformed tobacco (Nicotiana tabacum L.) plants with varying activities of the
      key enzyme of ammonia assimilation, ferredoxin-glutamine-alpha-ketoglutarate
      aminotransferase (Fd-GOGAT; EC 1.4.7.1), were used to examine the roles of
      ammonium, glutamine (Gln) and alpha-ketoglutarate (alpha-KG) in the regulation of
      nitrate reductase (NR; EC 1.6.6.1) transcript abundance. In wild-type leaf discs,
      NR mRNA abundance was increased following feeding with NO3-, sucrose and alpha-KG
      and decreased by feeding Gln. In air, leaves with decreased GOGAT accumulated Gln
      and alpha-KG simultaneously; this was accompanied by increased NR transcripts.
      The inhibition of NR transcription by Gln observed in leaf-disc experiments was
      therefore not observed in the low-Fd-GOGAT plants that accumulate Gln in vivo.
      The results suggest that the negative effect of Gln on NR transcript abundance
      was offset by high alpha-KG and that the relative amounts of alpha-KG and Gln are
      more important in controlling NR gene transcription than the concentration of
      either metabolite alone.

PMID- 11469593
TI  - A small family of novel CuZn-superoxide dismutases with high isoelectric points
      in hybrid aspen.
AB  - Several CuZn-superoxide dismutases (SODs; EC 1.15.1.1) were cloned from hybrid
      aspen (Populus tremula L. x tremuloides Michx.). Two of the cloned genes encode
      representatives of a novel type of CuZn-SOD and we named it HipI-SOD because of
      its high isoelectric point (> or =9). The SODs were cloned by screening a cDNA
      library with a probe based on a Scots pine (Pinus sylvestris L.) CuZn-SOD that is
      predominantly located extracellularly. The expression pattern of HipI-SOD was
      examined using a Northern blot technique and compared with the expression
      patterns of cytosolic and chloroplastic SODs. Distinct expression patterns were
      observed for the three types of CuZn-SOD, with HipI-SODs showing strong
      expression in apical tissues. Southern blots as well as protein analysis suggest
      that these novel HipI-SODs belong to a small gene family, one member of which
      might be monomeric.

PMID- 11469594
TI  - Comparative analysis of HD2 type histone deacetylases in higher plants.
AB  - Zea mays (L.) histone deacetylase HD2 was identified as a new type of histone
      deacetylase (HDAC) unrelated to the well-known Rpd3p and Hdalp families but with
      sequence homology to peptidyl-prolyl cis-trans isomerases (PPIases). Here we show
      that HD2 is a multigene family with highly related members in various plant
      species. Gene analysis revealed a similar exon/intron structure in Arabidopsis
      thaliana (L.) Heynh. and Z. mays, and most of the sequences analyzed were
      demonstrated to possess an intron of the very rare AT-AC type.

PMID- 11469595
TI  - A new chloroplast envelope carbonic anhydrase activity is induced during
      acclimation to low inorganic carbon concentrations in Chlamydomonas reinhardtii.
AB  - Using mass-spectrometric measurements of 18O exchange from 13C18O2 we determined
      the activity of carbonic anhydrase (CA; EC 4.2.1.1) in chloroplast envelope
      membranes isolated from Chlamydomonas reinhardtii cw-15. Our results show an
      enrichment of CA activity in these fractions relative to the activity in the
      crude chloroplast. The envelope CA activity increased about 8-fold during the
      acclimation to low-CO2 conditions and was completely induced within the first 4 h
      after the transfer to air levels of CO2. The CA-activity was not dissociated from
      envelope membranes after salt treatment. In addition, no cross-reactivity with
      other CA isoenzymes of Chlamydomonas was observed in our chloroplast envelope
      membranes. All these observations indicated that the protein responsible for this
      activity was a new CA isoenzyme, which was an integral component of the
      chloroplast envelopes from Chlamydomonas. The catalytic properties of the
      envelope CA activity were completely different from those of the thylakoid
      isoenzyme, showing a high requirement for Mg2+ and a high sensitivity to
      ethoxyzolamide. Analysis of the integral envelope proteins showed that there were
      no detectable differences between high- and low-inorganic carbon (Ci) cells,
      suggesting that the new CA activity was constitutively expressed in both high-
      and low-Ci cells. Two different high-Ci-requiring mutants of C. reinhardtii, cia
      3 and pmp-1, had a reduced envelope CA activity. We propose that this activity
      could play a role in the uptake of inorganic carbon at the chloroplast envelope
      membranes.

PMID- 11469596
TI  - Molecular and biochemical characterization of endo-beta-mannanases from
      germinating coffee (Coffea arabica) grains.
AB  - The activity of endo-beta-mannanase ([1-->4]-beta-mannan endohydrolase EC
      3.2.1.78) is likely to be central to the metabolism of cell wall mannans during
      the germination of grains of coffee (Coffea spp.). In the present paper, we
      report the cloning and sequencing of two endo-beta-mannanase cDNAs (manA and
      manB) by different strategies from Coffea arabica L.. The manA cDNA was obtained
      by the use of oligonucleotides homologous to published sequences of other endo
      beta-mannanases and manB by the use of oligonucleotides deduced from a purified
      enzyme from coffee. ManA and B proteins share about 56% sequence homology and
      include highly conserved regions found in other mannan endohydrolases.
      Purification of the activity by chromatography followed by separation by two
      dimensional electrophoresis and amino acid sequencing demonstrated the existence
      of at least seven isomers of the ManB form. The existence of multiple manB genes
      was also indicated by Southern analysis, whereas only one or two gene copies were
      detected for manA. Northern hybridizations with manA- and manB-specific probes
      showed that mRNA transcripts for both cDNAs were present at the same periods of
      bean germination with transcript peaks at 20 days after imbibition of water
      (DAI). Transcripts were not detected during grain maturation or in the other
      tissues such as roots, stems, flowers and leaves. The peak endo-beta-mannanase
      activity occurred at approximately 28 DAI and was not detected in grains prior to
      imbibition. Activity and mRNA levels appeared to be tightly co-ordinated. Tests
      of substrate specificity with the purified ManB enzyme showed that activity
      required a minimum of five mannose units to function efficiently.

PMID- 11469597
TI  - Low-expression genes induced by nitrogen starvation and subsequent sexual
      differentiation in Chlamydomonas reinhardtii, isolated by the differential
      display technique.
AB  - Genes that are expressed upon a shift to nitrogen-free medium, an event that
      initiates gametogenesis, were identified in Chlamydomonas reinhardtii by using
      the differential display technique. Ten different cDNAs were isolated and shown
      to have increased levels of their transcripts upon removal of the nitrogen
      source. The initial kinetics of RNA accumulation allowed an ordering of the genes
      with respect to the timing of their expression, with individual genes being
      expressed very early, early, intermediately, or late after induction. For very
      early genes, significantly increased transcript levels were detected within 30
      min. This fast response suggests that gene expression is rapidly activated after
      removal of the nitrogen source. The accumulation of transcripts from the very
      early, early, and intermediate genes preceded the appearance of mating
      competence. Though transcript levels of several very early genes fluctuated
      during subsequent incubation in nitrogen-free medium, most of them exhibited
      maxima when the highest level of mating competence was attained. One of these
      very early genes was shown to encode a urate oxidase type-II enzyme.

PMID- 11469598
TI  - Oxytropism: a new twist in pollen tube orientation.
AB  - Chemical gradients and structural features within the pistil have been previously
      proposed as factors determining the directionality of pollen tube growth. In this
      study, we examine the behavior of pollen of eight species germinated in a dynamic
      oxygen gradient. While the germination rates of some species decreased directly
      with decreasing oxygen tension, other species showed no decrease in germination
      at oxygen tensions as low as 2 kPa. In one species, germination was consistently
      greater at decreased oxygen tensions than at ambient atmospheric levels. In three
      of the eight species tested, the developing pollen tube showed clear directional
      growth away from the more-oxygenated regions of the growth medium, while in one
      species growth was towards the more-oxygenated region. The remaining four species
      showed random tube growth. The pattern of oxytropic responses among the taxa
      suggests that this tropic behavior is both widespread and phylogenetically
      unpredictable.

PMID- 11469599
TI  - Biosynthesis of 2-methyl-3-buten-2-ol emitted from needles of Pinus ponderosa via
      the non-mevalonate DOXP/MEP pathway of isoprenoid formation.
AB  - The volatile hemiterpene 2-methyl-3-buten-2-ol (MBO) is emitted from the needles
      of several pine species from the Western United States and contributes to ozone
      formation in the atmosphere. It is synthesised enzymatically from dimethylallyl
      diphosphate (DMAPP). We show here that needles of Pinus ponderosa Laws.
      incorporated [1-2H1]-1-deoxy-D-xylulose (d-DOX) into the emitted MBO, but not D,L
      [2-13C]mevalonic acid lactone. Furthermore, MBO emission was inhibited by
      fosmidomycin, a specific inhibitor of the second enzyme of the mevalonate
      independent pathway of isopentenyl diphosphate and DMAPP formation, i.e. the 1
      deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP)
      pathway. We thus prove that MBO emitted from needles of P. ponderosa is primarily
      formed via the DOXP/MEP pathway.

PMID- 11469600
TI  - Chronic pelvic pain.

PMID- 11469601
TI  - Interstitial cystitis: a chronic inflammatory bladder condition.
AB  - Interstitial cystitis (IC) is a chronic inflammatory condition of the bladder
      wall, characterized by urinary frequency and urgency, and severe suprapubic
      and/or pelvic pain. Symptoms of IC resemble those of ordinary urinary tract
      infections. However, standard urine cultures are negative and antibiotic therapy
      offers no relief. Recent research indicates that IC may be much more common than
      was previously thought, affecting over 700,000 people in the US. More than 90% of
      those affected are women, many of whose lives are thoroughly disrupted by severe
      pain. Long overlooked and misdiagnosed, IC is only now beginning to be
      understood. Although there is no specific diagnostic test or marker for IC and no
      uniformly effective treatment, little more than a decade of research has yielded
      promising results. New diagnostic tests are currently being developed and new
      therapeutic modalities are in clinical trials. While science searches for answers
      to this devastating disease, patients living with pain deserve relief.

PMID- 11469602
TI  - Review on chronic pelvic pain from a urological point of view.
AB  - Chronic pelvic pain or interstitial cystitis (IC) is an enigmatic and frustrating
      condition to manage as physician and to cope with as patient. Patients report
      moderate to excruciating pain in the suprapubic and/or vaginal area, urgency and
      frequency (up to 50 micturitions per day), and disruption of their social life.
      Many patients are declared as drug addicted and neurotic. Social status and the
      number of sexual partners showed no correlation with incidence. Diagnosis of IC
      is made by exclusion. A number of pathophysiologic mechanisms have been proposed:
      changes in epithelial permeability, pelvic floor dysfunction, mastocytosis,
      activation of C-fibers, increase of nerve growth factors, and bradykinin. No
      single theory can explain IC.

PMID- 11469603
TI  - Gastroenterological causes of pelvic pain.
AB  - Chronic pelvic pain is a common condition, which accounts for up to 10% of
      gynecological consultations and for over a third of diagnostic laparoscopies. In
      addition to gynecological etiologies for the pelvic pain, the physician must also
      consider gastroenterological, urological, and neurological disease as a possible
      basis for the pain. This article discusses the major gastroenterological causes
      of pelvic pain.

PMID- 11469604
TI  - The male chronic pelvic pain syndrome.
AB  - Suffering chronic pain is a common and debilitating problem that significantly
      impairs the quality of life of affected patients. Because we continue to struggle
      with chronic pelvic pain disorders both diagnostically and therapeutically, a
      neuro-behavioral perspective should be used in an attempt to explain pathways and
      neurophysiological mechanisms, and to improve diagnostics and treatment of male
      pelvic pain. First, however, malignant and acute/chronic bacterial disease has to
      be excluded as a cause of chronic pain in every single case. Then diagnostic
      approaches should screen for lower urinary tract dysfunction, pelvic floor
      functional disorders, and disturbed reflex integrity within the pelvic area.
      Treatment approaches for the male chronic pelvic pain syndrome could be divided
      into causal and symptomatic. Causal treatment approaches try to influence basic
      mechanisms generating and supporting chronic pain. In most cases a symptomatic
      approach is needed to relieve pain immediately. Because generally accepted
      treatment protocols and studies are missing, the following approach in the
      individual patient is recommended: (1) symptomatic treatment for immediate pain
      relief, (2) diagnostic work-up, (3) causal treatment trial.

PMID- 11469605
TI  - Neurogenic inflammation and chronic pelvic pain.
AB  - Chronic pelvic pain is a puzzling disease entity. The pathophysiological
      mechanisms of chronic pelvic pain are not clear and current treatment strategies
      are often not successful, leaving patients as well as health care providers
      frustrated. In a subgroup of patients with chronic pelvic pain (e.g.,
      interstitial cystitis, irritable bowel syndrome, vulvar vestibulitis,
      prostatodynia/prostatitis, and loin pain/hematuria syndrome) inflammatory changes
      are observed, for which no etiology has been identified. These inflammatory
      changes might be due to neurogenic inflammation. Applying the concept of
      neurogenic inflammation to chronic pelvic pain provides new insights into the
      pathophysiological mechanisms of these pain syndromes, makes it possible to
      account for the heterogeneity and variability observed in the clinical
      presentation, and might lead to the development of novel therapies.

PMID- 11469606
TI  - Urodynamic features of the pelvic pain patient and the impact of neurostimulation
      on these parameters.

PMID- 11469607
TI  - Physical therapy management of pelvi/perineal and perianal pain syndromes.
AB  - Pelvic floor physical therapy is considered to be effective in the management of
      functional urogenital and anorectal disorders. A functioning pelvic floor is
      integral to increases in intra-abdominal pressure, provides rectal support during
      defecation, has an inhibitory effect on bladder activity, helps support pelvic
      organs, and assists in lumbopelvic stability. Coordinated release of the
      sphincters within a supporting extensible levator ani allows complete and
      effortless emptying. A major feature of pelvi/perineal and perianal pain
      syndromes commonly encountered by multidisciplinary clinicians is pelvic floor
      imbalance and incoordination. Precise pelvic floor and abdominal muscle
      coactivity, based on research, is used clinically. Motor and cognitive learning
      which can alter peripheral and central pain mechanisms and produce physical
      changes in the CNS, viscera, smooth and musculoskeletal tissues is the basis of
      physical therapy in pelvic floor and pelvic organ pain management.

PMID- 11469608
TI  - Diagnosis and treatment issues of chronic pelvic pain.
AB  - The diagnosis and management of pelvic pain presents a challenge to the medical
      practitioner. The approach should be systematic and organized to provide the best
      possible care. The aim of this article is to increase awareness among urologists
      so that they may be more able to understand and support their patients.

PMID- 11469609
TI  - The pelvic pain centre.
AB  - Pelvic pain is a symptom which, in many patients, may be chronic. Since pelvic
      pain is relatively unknown to many doctors, patients tend to consult many
      different physicians and are, as a whole, a difficult group to treat. All of
      these aspects together make it easy to understand that a specialised
      multidisciplinary centre is needed to treat pelvic pain patients. In this article
      a blueprint for such a centre is proposed. The structure of the building, the
      workers, the goals of this centre and the importance of education and research
      will be shown. Some aspects on the future of pelvic pain centres will conclude
      this article.

PMID- 11469610
TI  - Chronic perineal pain and lower urinary tract dysfunction--a clinical feature of
      the "Gulf War syndrome"?
AB  - A Persian Gulf War veteran presented to the University Neuro-Urology service for
      management of severe chronic perineal pain. The overall physical and neurological
      exam was unremarkable. However, the rectal exam and the urodynamic study revealed
      a severe pelvic floor dysfunction. A neuro-behavioral approach is recommended and
      discussed.

PMID- 11469611
TI  - Transperitoneal unstented ureteral reimplantation for injuries postgynecological
      surgery.
AB  - Pelvic ureteral injuries represent a serious surgical accident due to the
      potential damage they may cause to renal function. We report here the results of
      19 years of experience with reconstruction of distal ureteral injuries by
      transperitoneal unstented reimplantation. This was a prospective cohort study
      undertaken at Barao de Lucena and University Hospitals, Recife (Brazil). Forty
      seven patients with ureteral obstruction postgynecological surgery were routinely
      operated using the initial incision. The ureter was identified, dissected, and
      reimplanted through the peritoneal cavity. No stent was necessary. The average
      surgical time was 70 min (45-180 min). A psoas hitch or a Boari-Ockenblad bladder
      flap was required in six (12.8%) and four (8.5%) patients, respectively. Among 32
      patients without fistula, 28 (87.5%) had complete and four (12.5%) had partial
      hydronephrosis regression without clinical repercussions. The cure rate was 100%.
      There were no complications. Routine primary unstented distal ureteral
      reimplantation using the transperitoneal approach is an effective and safe
      treatment strategy for injuries following benign gynecological surgery.

PMID- 11469612
TI  - The effect of nitric oxide and peroxynitrite on rabbit cavernosal smooth muscle
      relaxation.
AB  - Nitric oxide (NO) mediates penile erection by inducing cavernosal smooth muscle
      relaxation. Superoxide anion (O2-) can influence the activity of NO by reacting
      with it to produce peroxynitrite (PN). This is a highly reactive species that is
      known to attack a variety of biological targets. It is far more reactive and
      damaging than its precursors. We therefore, investigated the effect of PN on
      rabbit cavernosal smooth muscle relaxation and compared it to NO. Cavernosal
      strips from nine adult New Zealand White rabbits were excised (n = 12 strips for
      each arm of the study) and mounted in organ baths. After pre-contraction with
      phenylephrine (PE) (100 microM) the strips were exposed to either NO or PN (1-100
      microM) and subsequent smooth muscle relaxations monitored. Some tissues were
      incubated with oxadiazoloquinoxalin-1-one (ODQ; 10 microM), an inhibitor of
      guanylyl cyclase, before the addition of NO or PN. NO and PN induced
      concentration-dependent relaxations in all strips. However, PN (IC50: 26 +/- 3.6
      microM) was significantly less potent than NO (IC50: 11 +/- 0.7 microM) [P <
      0.01]. Relaxation induced by NO was immediate and short-lived, with the tension
      returning to its original level. In contrast, PN-initiated relaxations were of a
      slower onset and more prolonged, with the tissues unable to recover tension.
      However, after several washouts the tissues were fully responsive to PE. Both NO-
      and PN-mediated relaxations were inhibited by ODQ, suggesting the involvement of
      cGMP in this process. Although PN mediates cavernosal smooth muscle relaxation,
      it is much less potent than NO. As PN is thought to play a role in a variety of
      pathologies where erectile dysfunction is prominent, it may also contribute to
      the pathogenesis of erectile dysfunction.

PMID- 11469613
TI  - A miniaturized self-contained single-use disposable quantitatitve test for
      hemoglobin A1c in blood at the point of care.
AB  - DRx HbA1c is a finger-stick (< or =10 microL) test for hemoglobin A1c (HbA1c)
      developed by Metrika, Inc., for rapid quantitative testing at the point of care.
      It incorporates microelectronics, optics, and dry reagent chemistry inside a self
      contained, integrated, single-use device. Test results (%HbA1c) are displayed in
      numeric form on the device's liquid crystal display within 8 min after sample
      application. Having no switches or buttons, DRx HbA1c self-activates upon
      addition of sample. It contains two dry reagent lateral flow strips, each having
      an HbA1c immunoassay test zone and a total hemoglobin (Hb) test zone. An on-board
      microprocessor calculates %HbA1c from the reflectances of the test zones. The
      microprocessor also corrects for lot-specific reagent characteristics and optical
      variation, in addition to checking electrical functioning and proper sample
      volume. For testing accuracy, subjects both with and without diabetes were
      recruited in order to obtain samples with a wide range of HbA1c values. Whole
      blood samples were analyzed using both DRx HbA1c units and a laboratory method
      (Bio-Rad DiaSTATT). DRx HbA1c testing was performed by laboratory personnel and
      by subjects who received brief training. Repeatability, linearity, sample volume
      tolerance, diluted sample stability and hematocrit tolerance of the DRx HbA1c
      test were assessed by trained laboratory personnel as described in the text. The
      linear %HbA1c range of the assay extended from approximately 3% to 15%. Hb was
      measurable from 6.8 to 20.0 g/dL, encompassing over 99.8% of the normal
      population. DRx HbA1c clinical sample test results (n = 50) correlated linearly
      to the Bio-Rad DiaSTAT method (r = 0.935) with slope and intercept values of
      0.994 and 0.003, respectively. The repeatability for %HbA1c was within 5-9% CV.
      We conclude that DRx HbA1c performance is closely equivalent to that of existing
      tests.

PMID- 11469614
TI  - Implications of point-of-care testing for hemoglobin A1c.

PMID- 11469615
TI  - Dual test diabetes screening project: screening for poor glycemic control in a
      large workplace population.
AB  - The objective of this study was to assess the efficacy of a dual test blood
      glucose/fructosamine home monitoring system to screen individuals in the
      workplace for poor glycemic control. Screening values qualifying individuals for
      90 days of additional monitoring were as follows: fasting blood glucose > or =126
      mg/dL, casual blood glucose > or =140 mg/dL, and/or fructosamine <310 micromol/L.
      Subjects with positive values were provided access to classroom instruction by a
      Certified Diabetes Educator. The population consisted of 100 males and 177
      females, ages 22-71 years, mean 49.7 years, with 12 males and 22 females
      reporting diabetes. Their ethnic backgrounds were 17.7% African American, 0.4%
      Asian, 1.8% Hispanic, 0.4% mixed, and 79.8% Caucasian reflecting the general
      United States population. A total of 26 males and 27 females had results
      indicating poor glycemic control. Of the known individuals with diabetes, seven
      of 12 males and 15 of 22 females had positive results. More males than females
      were unaware of their potential for diabetes but of those previously diagnosed
      with diabetes more females than males had poor glycemic control. A total of 31
      subjects tested positive for blood glucose, 39 tested positive for fructosamine,
      indicating a 15.1% (p < 0.005) improvement in detection chances with
      fructosamine. Cost per subject including equipment, supplies, and labor was
      $18.13. Study results indicate that the addition of a fructosamine test improves
      screening accuracy for large groups of people while retaining ease of use and
      affordability.

PMID- 11469616
TI  - Serum fructosamine as a screening test for type 2 diabetes.

PMID- 11469617
TI  - Vacuum-assisted lancing of the forearm: an effective and less painful approach to
      blood glucose monitoring.
AB  - A vacuum-lancet device was applied to the forearm for the purpose of obtaining
      capillary blood samples for glucose monitoring with minimal pain. In four
      clinical trials, a total of 215 individuals aged 12-77 years were tested four
      times using standard conditions and four times with either a different depth of
      lancing, different brand of lancet or a larger-sized device. The volume of blood
      collected using one-half atmosphere of vacuum in 40 sec was measured. The
      sensation and visual appearance of each lancet puncture on the forearm was
      recorded. Glucose was measured in forearm and in conventional fingerstick blood
      samples. The distribution of volumes was skewed to higher values with median
      values for each trial in the range of 3-10 microL. Ninety-five percent of the
      lancet sticks were judged as less painful than a fingerstick. Redness and
      bruising around the lanced sites were noted in some patients but disappeared
      within a few days. Overall correlation of the forearm versus fingerstick glucose
      values was 0.96. The vacuum-lancet device was very successful in obtaining
      capillary blood samples for glucose testing in a relatively painless manner.
      Incorporation of a glucose measuring system into the device might improve testing
      compliance among those who fear pain or the sight of blood.

PMID- 11469618
TI  - The use of silicon microfabrication technology in painless blood glucose
      monitoring.
AB  - A unique minimally invasive system for painless blood testing is now being
      commercialized for measurement of blood glucose concentration by diabetics. The
      novel component of this system, a consumable microsampling and assay device,
      consists of a tough, flexible silicon microneedle comparable in cross-section to
      a human hair integrated with a silicon microcuvette. This microneedle is capable
      of reliably taking a very small sample of whole blood completely painlessly,
      unlike sticks with the much larger metal lancet that must be used in all other
      current systems. The device permits a one-step process that avoids the need to
      transfer blood from a skin puncture to a test strip, thus minimizing blood
      required and possible mess. The small hand-held instrument containing the
      consumable is touched to the skin of the arm or any other part of the body, not
      necessarily the tip of the finger, and held there for one second. During this
      time, the microneedle is advanced and then withdrawn under microprocessor
      control, puncturing the skin and drawing less than 200 nanoliters of blood into
      the microcuvette, where the assay is performed automatically. The instrument
      calculates the blood glucose concentration, displays the result, and holds it in
      memory for recall. The consumable is produced by silicon microelectromechanical
      systems technology and can be produced in high volume at low unit cost. This
      technology shows promise of being extended to other analytes and to continuous
      monitoring.

PMID- 11469619
TI  - Telemedical care reduces hypoglycemias and improves glycemic control in children
      and adolescents with type 1 diabetes.
AB  - Education programs for intensive insulin therapy were found to be valuable in
      improving glycemic control, but, due to low prevalence of type 1 diabetes in
      children and adolescents, access to those programs varies considerably in rural
      areas. We report on a telemedical care program that overcomes geographical
      isolation of patients on intensive insulin therapy. Sixty-one children and
      adolescents under the age of 26 participated in a telemedical care program. They
      stored daily information on blood glucose, injected insulin, meals and exercise
      in a glucosemeter with electronic memory and transferred the data via modem go a
      remote diabetes center outside of the region. By individual telephone
      consultations from home, they reviewed the data with a diabetologist at the
      diabetes center and adjusted their intensive insulin therapy in order to achieve
      predefined treatment goals. Patients were trained for 19 (6-48) weeks in the
      program and measured blood glucose 4.9 (1.7-4.9) times daily. Compared to the run
      in-period, mean blood glucose had decreased (167 to 158 mg/dL, p < 0.01),
      standard deviation of blood glucose had decreased (81 to 70 mg/dL, p < 0.001),
      and frequency of hypoglycemia had decreased (5.2 to 3.3 in 4 weeks, p = 0.01) at
      the end of the program. The proportion of blood glucose values within the target
      range (80-180 mg/dL) had increased (47-55%, p < 0.001). HbAlc was reduced by 0.4%
      (-3.8 to +2.2%, p < 0.05). Telemedical care for intensive insulin therapy is
      safe, can improve glycemic control, and reduce the number of hypoglycemias in
      children and adolescents with type 1 diabetes.

PMID- 11469620
TI  - An intelligent diabetes software prototype: predicting blood glucose levels and
      recommending regimen changes.
AB  - Maintaining optimal blood glucose (BG) control is difficult for type 1 diabetes
      mellitus (T1DM) patients when typical daily regimens of food, insulin and
      exercise are altered. Artificial intelligence (AI) systems consisting of
      treatment algorithms calibrated through large datasets of patient specific
      information may offer a solution. Such a system can predict BG level changes
      resulting from regimen disturbances and recommend regimen changes for
      compensation. A software prototype based on neural network, fuzzy logic, and
      expert system concepts was developed and evaluated to determine feasibility and
      efficacy of a patient specific prediction model. BG data are the primary driver
      for adapting existing functions to patient specific prediction algorithms. Mean
      absolute percent error (MAPE) between actual and predicted BG values from inputs
      of daily insulin, food, and exercise information for an T1DM test subject was
      10.5% using a calibrated model. The prototype is limited by the requirement for a
      rigid testing schedule, human error and situational circumstances such as alcohol
      consumption, illness, infection, stress, and significant hormonal imbalances. No
      significant conclusions regarding model validity can be drawn due to limited
      evaluation process and subject sample size, although the prototype has
      demonstrated viability as a learning tool for diabetes patients. Increased
      impetus for further development of this prototype and similar AI models may
      materialize when more effective diagnostic and data capture tools become
      available to reduce testing and improve accuracy of the model with more input
      data.

PMID- 11469621
TI  - Building telemedicine systems for supporting decisions in diabetes care: a report
      from a running experience.
AB  - This paper describes some issues that should be investigated to implement
      telemedicine systems designed for effectively supporting decisions in diabetic
      patients management, namely situation assessment, information sharing, and
      knowledge management. The solutions and experiences carried on in this field
      within a European Union (EU)-funded project, called T-IDDM (Telematic Management
      of Insulin Dependent Diabetes Mellitus), are reported.

PMID- 11469622
TI  - Tele-ophthalmology via stereoscopic digital imaging: a pilot project.
AB  - Diabetic eye disease is present in remote communities across Canada. A pilot
      study was designed to assess the feasibility of stereoscopic digital imaging to
      identify levels of diabetic retinopathy via teleophthalmology. Diabetic patients
      were assessed for diabetic retinopathy by seven field stereoscopic digital
      imaging through a dilated pupil. Images were transferred by satellite to a
      tertiary eye center for review by a retinal specialist. Images were viewed
      stereoscopically on a video monitor, with grading of all images using a modified
      Early Treatment Diabetic Retinopathy Study (ETDRS) classification. Patients found
      to have treatable diabetic retinopathy were transferred to a tertiary eye center
      for assessment and treatment by a retinal specialist. One hundred patients (199
      eyes) had stereoscopic digital imaging of the retina. Microaneurysms were
      identified in 70 eyes, hard exudates in 31 eyes. Two eyes were identified with
      neovascularization of the disc (NVD) and 15 eyes with clinically significant
      macular edema (CSME). All eyes identified by stereoscopic digital imaging with
      treatable disease were confirmed by clinical examination with contact lens
      biomicroscopy. Stereoscopic digital imaging of the retina enables the
      identification of diabetic retinopathy. Further research is needed to delineate
      the sensitivity and specificity of stereoscopic digital imaging when compared to
      slide film and clinical examination.

PMID- 11469623
TI  - Oxidative stress evaluation in diabetes.
AB  - Over the recent years, researches have focused their attention on the pathologic
      role of free radicals in a variety of diseases, among which the most important
      are atherosclerosis, cancer, and diabetes. The set of intracellular and
      extracellular conditions that leads to chemical or metabolic generation of
      reactive species is termed "oxidative stress." The susceptibility to oxidative
      stress is a function of the overall balance between the factors that exert
      oxidative stress and those that exhibit antioxidant capability. There is
      currently great interest in the potential contribution of increased oxidative
      stress to the development of complications in diabetes mellitus. Direct
      measurement of oxidative stress in vivo is a very complex question, because free
      radicals are highly reactive, have a very short life, and are present in very low
      concentrations. Thus, indirect methods, used for measuring secondary products of
      oxidative stress, are rather unspecific and may give conflicting data.
      Nitrotyrosine detection in plasma and tissues may be a useful method to
      demonstrate peroxynitrite-mediated damage. The total radical-trapping potential
      (TRAP) in plasma represents a more reliable estimation of serum antioxidant
      capability than the measurement of each known antioxidant. The detection of
      increased levels of oxidation products in tissue and biological fluids is
      important to investigate the relation between free radical production and the
      development of pathology. This hypothesis suggests the possibility of a
      therapeutic intervention with antioxidant agents. The identification of a useful
      marker to assess the effect of antioxidants on oxidative stress seems to be
      mandatory.

PMID- 11469624
TI  - New insights into the pathophysiology of diabetic retinopathy: potential cell
      specific therapeutic targets.
AB  - Diabetic retinopathy, a leading cause of vision impairment, is classically
      defined by its vascular lesions. This review examines how diabetes affects
      vascular cells, as well as neurons, macroglia, and microglia. The cellular and
      clinical elements of diabetic retinopathy have many features of chronic
      inflammation. Understanding the individual cell-specific and global inflammatory
      changes in the retina may lead to novel therapeutic approaches to prevent vision
      loss.

PMID- 11469625
TI  - Modification of the environment is not the most efficient way to prevent type 1
      diabetes.

PMID- 11469626
TI  - Short user comments ('sound bites') regarding usage of AIDA v4-
      http://www.2aida.org--an interactive educational diabetes simulator.

PMID- 11469627
TI  - The MiniMed continuous glucose monitoring system.

PMID- 11469628
TI  - Efficacy and reliability of the continuous glucose monitoring system.

PMID- 11469629
TI  - Continuous glucose monitoring in previously unstudied population subgroups.

PMID- 11469630
TI  - Clinical utility of the continuous glucose monitoring system.

PMID- 11469631
TI  - Using the continuous glucose monitoring system to improve the management of type
      1 diabetes.

PMID- 11469632
TI  - Role of the continuous glucose monitoring system in pediatric patients.

PMID- 11469633
TI  - Continuous glucose monitoring in youth with type 2 diabetes: overcoming barriers
      to successful treatment.

PMID- 11469634
TI  - Type 2 diabetes mellitus.

PMID- 11469635
TI  - The role of continuous glucose monitoring in gestational diabetes mellitus.

PMID- 11469636
TI  - The economic burden of diabetes and the benefits of improved glycemic control:
      the potential role of a continuous glucose monitoring system.

PMID- 11469637
TI  - Continuous glucose monitoring system: a new approach to the diagnosis of diabetic
      gastroparesis.

PMID- 11469638
TI  - Hypoglycemia and the hypoglycemic unawareness syndrome.

PMID- 11469639
TI  - Office logistics: implementation of the continuous glucose monitoring system in
      clinical practice.

PMID- 11469640
TI  - Psychological motivation and patient education: a role for continuous glucose
      monitoring.

PMID- 11469641
TI  - Effect of selection for improved body composition on muscle and meat
      characteristics of broilers from experimental and commercial lines.
AB  - Meat quality (pH, color, and drip loss) and muscle characteristics (composition
      and metabolic pattern) were compared among four broiler lines: an experimental
      line, a commercial line selected for increased body weight and breast yield, and
      the respective unselected control lines. By comparison to their controls, the
      commercially selected birds exhibited higher body weight and breast yield (127
      and 61%, respectively), whereas only breast yield was increased (21%) in the
      experimental selected line. Commercial selection resulted in higher protein
      content and lower moisture in the breast muscle. Experimental and commercial
      selection decreased the heme pigment content, which could explain why breast meat
      of the selected birds was more pale and less red. This change in the color did
      not correspond to a pale, soft, and exudative (PSE) defect, as the selected birds
      did not exhibit excessive drip loss. By comparison with their controls, both
      selected lines showed a lower rate and extent of pH decline postmortem, which was
      consistent with the lower glycolytic potential they also exhibited. However, no
      significant changes in the metabolic pathways of breast muscle, as measured by
      enzyme activities, could be found to explain differences in rates of pH decline
      among lines. This study did not support the idea that selection had a negative
      impact on meat quality, despite evidence of modified breast metabolism.

PMID- 11469642
TI  - Estimation of the genetic parameters of meat characteristics and of their genetic
      correlations with growth and body composition in an experimental broiler line.
AB  - Genetic parameters of breast meat characteristics [pH 15 min postmortem
      (pH15min), ultimate pH (pHu), CIELAB color parameters (L*, lightness; a*,
      redness; b*, yellowness) and drip loss (DL)] as well as their genetic
      correlations with BW and body composition [breast yield (BRY) and abdominal fat
      percentage (AFP)] were estimated in an experimental meat-type chicken line.
      Heritability of the pH of meat was high for pHu (0.35 +/- 0.03) and even more so
      for pH15min (0.49 +/- 0.01). Color parameters appeared to be the most heritable
      traits, with heritability values ranging from 0.50 to 0.57. Drip loss
      heritability was estimated at 0.39 +/- 0.04. The rate and the extent of pH
      decline seemed to be controlled by different genes, as shown by the extremely low
      estimated genetic correlation (0.02 +/- 0.04) between pH15min and pHu. The
      ultimate pH of the meat was genetically very strongly related to its lightness (
      0.91 +/- 0.02) and water-holding capacity (-0.83 +/- 0.04). These results suggest
      that selection for pHu could be exploited to prevent increased incidence of pale
      and exudative meat. The pH15min was poorly correlated with the other meat
      characteristics, with estimated correlations of 0.13, -0.23, 0.05, and -0.29 for
      L*, a*, b*, and DL, respectively. These results may be explained by the fact
      that, in our experimental conditions, pH15min remained high (between 6.01 and
      6.75). Body weight and BRY exhibited poor genetic correlations (ranging from 
      0.06 to 0.13) with the pH of the meat at 15 min and 24 h postmortem. Both of the
      former traits were moderately negatively correlated with a* and b* values. A
      significant negative genetic correlation was observed between abdominal fatness
      and pHu. These results do not support the idea that selection for growth and
      breast development has a detrimental effect on breast meat quality even if, in
      the long term, the color intensity could be decreased.

PMID- 11469643
TI  - Estimation of genetic parameters for ascites syndrome in broiler chickens.
AB  - Genetic parameters for the ascites syndrome (AS) were estimated for meat-type
      chickens. Data had been collected over 11 generations of selection for body
      weight and other traits within two distinct breeds (Cornish and White Rock).
      Linear methods (LM) were used to estimate genetic parameters and also to analyze
      a binary measure of survival. Survival analyses (SA) were also conducted to
      estimate the effects of various factors influencing the incidence of AS by
      evaluating the number of days that the birds survived. The animal model was used
      exclusively with linear methods. Heritabilities (h2) on the liability scale were
      0.12 +/- 0.02 and 0.22 +/- 0.01 in the White Rock and Cornish breeds,
      respectively; however, the genetic correlation (r(g)) with body weight was not
      possible to estimate due to the low prevalence of the defect trait studied (1.5%
      in the Cornish and 1.1% in the White Rock). Because males are more prone to AS,
      the h2 using the male records only were 0.22 +/- 0.017 and 0.41 +/- 0.009, and
      the r(g) were 0.35 +/- 0.007 and 0.22 +/- 0.009 in the dam and sire populations,
      respectively. In conclusion, the heart defect investigated was heritable and had
      a positive genetic correlation with body weight.

PMID- 11469644
TI  - Genetic analysis of a selection experiment on the growth curve of chickens.
AB  - A selection experiment on the shape of the growth curve was performed on meat
      type chickens through combined selection on juvenile and adult BW. Line X-+ was
      selected for low BW at 8 wk (BW8) and high BW at 36 wk (BW36). Line X+- was
      selected for high BW8 and low BW36. Line X++ was selected for high BW8 and BW36,
      and X-- was selected for low BW8 and BW36. Line X00 was maintained as an
      unselected control. Data on the first 14 generations (i.e., 38,693 birds) were
      used. The growth curve was modeled using a Gompertz function on 7,143 birds that
      were weighed regularly. Selection for higher BW8 increased BW from 4 to 16 wk,
      initial specific growth rate, and maturation rate and decreased age at
      inflection. Selection for higher BW36 resulted in increased BW36, asymptotic BW,
      and estimated BW at hatching. Body weights were more modified in Lines X++ and X-
      , but the growth curve parameters changed more in Lines X-+ and X-- than in Lines
      X++ and X+-.

PMID- 11469645
TI  - Effect of breed and age of hens on the yolk to albumen ratio in two different
      genetic stocks.
AB  - A commercial egg-type chicken (ISA Brown; CEC) and a dual-purpose pure breed of
      the Korean Native Chicken (KNC) were compared for yolk to albumen (Y:A) ratio and
      their major egg characteristics at seven different ages. The eggs from KNC were
      significantly (P < 0.01) lighter in egg, albumen, and shell weight than those
      from CEC. However, the yolk weight and Y:A ratio of the eggs from KNC were
      significantly (P < 0.01) heavier or larger than the ones of CEC. The effect of
      age on the yolk, shell weight, and shell thickness was highly significant (P <
      0.01), whereas significant differences were not found for Y:A ratio and other
      major egg components. The breed-by-age-of-hen interactions were significant for
      shell weight (P < 0.03) and shell thickness (P < 0.01). The yolk, albumen, and
      shell weight were positively (P < 0.001) associated with egg weight in both
      breeds. The association of Y:A ratio with egg weight in both breeds also were
      highly significant (P < 0.001) but negative. The results of the present study
      indicated that the different effects on the Y:A ratio were due to breed rather
      than age. Results suggest that the eggs from KNC are more desirable for use in
      products made of yolk than for consumption as table eggs.

PMID- 11469646
TI  - A model for individual egg production in chickens.
AB  - Our primary objective was to improve on an existing model for the individual
      weekly egg production curve by modeling the curve as a sum of logistic functions:
      one for the increasing phase of production and a sum for the decreasing phases.
      To illustrate the model, we used four data sets from two pairs of individuals.
      For these data, the model consisted of an increasing phase and a single
      decreasing phase of production: y(t) = m k1((1 - e(-t))/(1 + e(-t))) - m(k1 -
      k2)((1 - e(-t))/(1 + e(-(t-c2)))) where y(t) is egg production at week t, m is
      maximum production during a specific time interval, k1 is proportion of maximum
      production for the increasing phase, k2 is proportion of maximum production for
      the decreasing phase, and c2 is point of inflection from the upper level of the
      increasing phase to the lower level of the decreasing phase; thus, c2 is a
      measure of persistency of egg production. For one pair of individuals, production
      was about 88% of maximum (k1) for the increasing phase and about 76% of maximum
      (k2) for the decreasing phase. For the other pair, production was about 91% of
      maximum (k1) for the increasing phase and about 75% of maximum (k2) for the
      decreasing phase. Persistency (c2) was about 25 wk for one pair and about 28 wk
      for the other. Predicted total 52-wk production was within one or two eggs of
      actual production. The secondary objective was to improve estimation of model
      parameters by summarizing egg production data by 1-wk, 2-wk, or 4-wk intervals
      and by using cumulative egg production instead of weekly production. For weekly
      production, estimates of parameters changed only slightly, as intervals increased
      from 1 wk to 2 wk or to 4 wk. Predicted total 52-wk production, however,
      decreased up to five eggs as interval increased from 1 wk to 4 wk. For cumulative
      egg production by time t, Yt, the model was Yt = 7 k1[2 Ln((1 + e(t))/2) - t] -
      7(k1 - k2)[(1 + e(-2)2) Ln((e(c2) + e(t))/(1 + e2c)) - te(-c2)]. For cumulative
      production, estimates of parameters changed only slightly, if at all, as
      intervals increased from 1 wk to 4 wk. Predicted 52-wk production, however,
      approached the actual number as interval increased from 1 wk to 4 wk. Prediction
      of annual (52-wk) egg production based on part-record production for only the
      first 22 wk might lead to over-prediction because persistency of production
      lasted longer than the part record. Genetic gain from selection to improve annual
      production, therefore, might be increased if selection accounted for persistency
      of production and for the multiphasic shape of the individual egg production
      curve, and if data were summarized by 4-wk intervals and cumulated.

PMID- 11469647
TI  - Estimating body weight and body composition of chickens by using noninvasive
      measurements.
AB  - The major objective of this research was to develop equations to estimate BW and
      body composition using measurements taken with inexpensive instruments. We used
      five groups of chickens that were created with different genetic stocks and
      feeding programs. Four of the five groups were from broiler genetic stock, and
      one was from sex-linked heavy layers. The goal was to sample six males from each
      group when the group weight was 1.20, 1.75, and 2.30 kg. Each male was weighed
      and measured for back length, pelvis width, circumference, breast width, keel
      length, and abdominal skinfold thickness. A cloth tape measure, calipers, and
      skinfold calipers were used for measurement. Chickens were scanned for total body
      electrical conductivity (TOBEC) before being euthanized and frozen. Six females
      were selected at weights similar to those for males and were measured in the same
      way. Each whole chicken was ground, and a portion of ground material of each was
      used to measure water, fat, ash, and energy content. Multiple linear regression
      was used to estimate BW from body measurements. The best single measurement was
      pelvis width, with an R2 = 0.67. Inclusion of three body measurements in an
      equation resulted in R2 = 0.78 and the following equation: BW (g) = -930.0 + 68.5
      (breast, cm) + 48.5 (circumference, cm) + 62.8 (pelvis, cm). The best single
      measurement to estimate body fat was abdominal skinfold thickness, expressed as a
      natural logarithm. Inclusion of weight and skinfold thickness resulted in R2 =
      0.63 for body fat according to the following equation: fat (%) = 24.83 + 6.75
      (skinfold, ln cm) - 3.87 (wt, kg). Inclusion of the result of TOBEC and the
      effect of sex improved the R2 to 0.78 for body fat. Regression analysis was used
      to develop additional equations, based on fat, to estimate water and energy
      contents of the body. The body water content (%) = 72.1 - 0.60 (body fat, %), and
      body energy (kcal/g) = 1.097 + 0.080 (body fat, %). The results of the present
      study indicated that the composition of a chicken's body could be estimated from
      the models that were developed.

PMID- 11469648
TI  - Effect of age at molting on postmolting performance.
AB  - Molt was induced at the 431, 501, or 571 d, in Lohmann (L) and Hy-Line W-77 (H)
      hens, by 8 or 14 d, respectively, of feed withdrawal followed by a rest period of
      16 d. Induced molt resulted in increases in egg production, numbers of intact
      eggs, egg mass per housed or surviving hen, and shell quality and in decreases in
      egg breakage (not significant), mortality, and culling. Egg weight was only
      slightly affected by molt, and the EW of hens induced to molt at 431 or 501 d of
      age were slightly lower than those of the unmolted hens or of those induced to
      molt at 571 d. Both strains reacted similarly to molt, although the L hens
      responded better, and expressed their responses more intensively when induced to
      molt earlier (431 d). This finding suggests that although different breeds have
      some effects of molt in common, molt protocols should be finely tuned for each
      breed. Total intact egg production and egg mass of the molted hens became higher
      than those of the unmolted hens at 650 to 728 d, which suggests that no benefit
      would be achieved by rearing molted hens for less than 700 to 730 d.

PMID- 11469649
TI  - Immune response and resistance to infectious bursal disease virus of chicken
      lines selected for high or low antibody response to Escherichia coli.
AB  - Two experimental broiler lines were developed by divergent selection for high
      (HH) and low (LL) antibody response to Escherichia coli. Antibody response of
      these lines to immunization with a commercial vaccine (whole inactivated virus,
      WIV) against infectious bursal disease virus (IBDV) or with proteins VP2 and VP3
      of that virus, and their resistance to challenge with a virulent IBDV, were
      tested. The study was performed with 213 male and female chicks from the tenth
      generation of the HH and LL lines. At 15 d of age, after disappearance of
      maternal antibodies, chicks from each line were randomly divided into four groups
      and injected with WIV, VP2, VP3, or adjuvant alone as a negative control. Chicks
      were bled 18 d postinjection, and antibody titers were determined by ELISA. Ten
      days later, the chicks were challenged with a virulent strain of the virus and
      killed after 10 d; the ratio of bursa of Fabricius to 100 g BW was determined for
      each bird. Significant differences in antibody titers were found among immunized
      and control chicks. Chicks from the HH line exhibited significantly higher
      antibody titers than LL chicks in response to WIV and VP2 vaccines but not to VP3
      vaccine. Following challenge, bursa weight (relative to BW) of HH and LL chicks
      vaccinated with WIV and VP2 was significantly higher (P < 0.01) than that of
      chicks vaccinated with VP3 or the challenged unvaccinated control. No difference
      was found in this parameter between the latter two groups. Possible explanations
      for the differences in the line response to VP2 and VP3 are discussed.

PMID- 11469650
TI  - Interactions and antigen dependence of dietary n-3 and n-6 polyunsaturated fatty
      acids on antibody responsiveness in growing layer hens.
AB  - Effects of four levels of dietary linoleic acid (LA), an n-6 fatty acid, and four
      levels of alpha-linolenic acid (LNA), an n-3 fatty acid, and their interactions
      on immune responses in growing layer hens were studied. Immune responses were
      induced by injection with keyhole limpet hemocyanin (KLH) or Mycobacterium
      butyricum particles at 35 d of age. Antibody (Ab) responses were measured until
      21 d after immunization. In addition, delayed-type hypersensitivity, lymphocyte
      proliferation, weekly feed intake, and BW gain were studied. At Day 7 after
      immunization, anti-M. butyricum titers in the M. butyricum-immunized hens were
      decreased by the increase of dietary LA (P < 0.05). In the period from 10 to 14 d
      after immunization, anti-KLH Ab titers in KLH-immunized animals were affected by
      the interaction of dietary LA with LNA (P < 0.01). High dietary levels of LA or
      LNA increased the anti-KLH Ab response. However, at high levels of dietary LA and
      LNA, anti-KLH Ab titers were not increased. In the same period, anti-M. butyricum
      Ab titers of M. butyricum-immunized hens were affected by the interaction of
      dietary LA with LNA (P < 0.05). At low levels of LA and LNA, increased LA levels
      decreased the Ab response, whereas increased LNA levels at low LA levels hardly
      affected the anti-M. butyricum response. At a high level of LA, increased dietary
      LNA increased the anti-M. butyricum response. In vitro proliferation of
      peripheral blood leukocytes after stimulation with concanavalin A (ConA) was
      higher in chickens with a high level of dietary LNA. Feed intake decreased when
      the dietary levels of LA or LNA increased. However, BW gain was not affected by
      dietary treatments. Feed conversion was more efficient in birds fed high levels
      of LA and LNA. The present study indicates that various factors affect the Ab
      responses. First, the interaction of n-6 and n-3 polyunsaturated fatty acids
      (PUFA) is more important than the separate effects of n-3 or n-6. Second, the
      actions of dietary PUFA were different between antigens of a different nature.
      Third was the nature of the antigen affects when dietary PUFA exert their actions
      and the persistence of these effects. The presence of these multiple factors
      affecting immune responses should be considered when comparing effects of dietary
      PUFA on immune responses.

PMID- 11469651
TI  - Immune responses and resistance to Eimeria acervulina of chickens divergently
      selected for antibody responses to sheep red blood cells.
AB  - Resistance to Eimeria acervulina was measured in two lines of chickens that had
      been divergently selected for high (H line) or low (L line) antibody (Ab)
      responses to SRBC, and in a randombred control (C) line originating from the same
      parental stock. Fecal oocyst output of cocks from the three lines from the 17th
      generation was estimated after primary and secondary infection with 2 x 10(5)
      oocysts. In addition, Ab responses to E. acervulina oocyst antigen and cellular
      immune responses in vitro to E. acervulina antigen were measured after primary
      and secondary infection with E. acervulina. No significant line differences were
      found with respect to fecal oocyst output after primary infection. Only at the
      end of the primary infection period, i.e., Day 15 postprimary infection, was a
      significantly lower fecal oocyst output found in the H line as compared to the C
      and L lines. After secondary infection, significantly higher fecal oocyst output
      was found in the C line. Significantly higher Ab response after primary and
      secondary infection were found in the H and C lines as compared to the L line. No
      line differences were found for cellular immune responses to E. acervulina oocyst
      antigen. These observations imply that selection for enhanced humoral immunity to
      SRBC did not result in enhanced resistance to E. acervulina in terms of fecal
      oocyst output. However, the H line might expel E. acervulina more rapidly than
      the other two lines. The absence of line differences in resistance to Eimeria is
      discussed with respect to the role of the humoral immune response.

PMID- 11469652
TI  - Maternal dietary alpha-linolenic acid (18:3n-3) alters n-3 polyunsaturated fatty
      acid metabolism and liver enzyme activity in hatched chicks.
AB  - We investigated the effects of dietary alpha-linolenic acid (LNA; 18:3n-3) of
      laying hens on the fatty acid composition of liver microsomes and activity of
      delta-6 desaturase in hatched chicks. Laying hens were fed wheat-soybean meal
      based diets with (Flax) or without ground flax (control). At Day 21 of feeding,
      fertile eggs were collected and incubated. On the day of hatching, chicks (n = 6)
      were killed, and liver microsomes were isolated and assayed for delta-6
      desaturase enzyme activity. The total n-3 fatty acids in the Flax eggs was 13.0%
      compared with 2.3% (P < 0.001) in the control group. LNA was the major n-3 fatty
      acid in the Flax eggs and constituted 10%. The long-chain n-3 polyunsaturated
      fatty acids (PUFA) (20:5n-3, 22:5n-3, and 22:6n-3) constituted 3.1% in Flax eggs
      compared with 1.5% in control eggs. Docosahexaenoic acid (22:6n-3) composed 2.1
      and 1.2% in Flax and control eggs (P < 0.05), respectively. The liver microsomes
      of Flax chicks incorporated higher 18:3n-3, 20:5n-3, and 22:5n-3 (P < 0.05) with
      a concomitant reduction in 20:4n-6, 22:4n-6, and 22:5n-6 compared with control
      chicks (P < 0.05). The delta-6 desaturase activities in Flax and control groups
      were 49.4 and 82.8 pmol/min per mg of protein, respectively (P < 0.05). These
      results demonstrate the role of maternal and yolk n-3 fatty acids in modulating
      the activity of rate-limiting enzymes for PUFA synthesis in hatched chicks.

PMID- 11469653
TI  - Effects of biogenic amines on growth and the incidence of proventricular lesions
      in broiler chickens.
AB  - Biogenic amines have been implicated in a malabsorption syndrome characterized by
      decreases in feed efficiency and enlargement of the proventriculus. Two studies
      were conducted to determine the effects of two common biogenic amines, histamine
      (HIS) and cadaverine (CAD), on broiler growth and the incidence of pathologies
      associated with proventriculitis. In the first experiment, broiler chicks were
      fed diets containing 0, 0.01, 0.05, 0.1, and 0.2% HIS, and in the second
      experiment chicks were fed diets containing 0, 0.1, and 0.2% HIS, 0.1% CAD, or a
      combination of 0.1% HIS and 0.1% CAD. Histamine at 0.1 and 0.2% or the
      combination of HIS and CAD (0.1% each) reduced body weight and feed conversion at
      21 d of age. Histamine (0.2%) or the combination of 0.1% HIS and 0.1% CAD
      increased the circumference of the gastric isthmus 14 and 16%, respectively, and
      the relative weight of the proventriculus by 21 and 36%, respectively. Histamine
      and CAD increased the total number, incidence, and severity of gizzard erosion
      and proventricular ulcers (plaques), and decreased the prominence of gastric
      papillae by 9 to 108%, depending on the lesion and level of biogenic amine.
      Dietary HIS (0.2%) increased putrescine by 91% and spermidine by 41% in
      proventriculus, and dietary CAD increased tissue CAD to detectable levels.
      Analysis of 49 commercially available, animal by-product feedstuffs suggests that
      if biogenic amines were the singular cause of proventriculitis, the current
      industry levels of dietary animal protein (5 to 10%) would not compromise growth
      performance.

PMID- 11469654
TI  - The effect of early feeding on growth and small intestinal development in the
      posthatch poult.
AB  - Poults with early access to feed in the hatchery or turkey house grew more than
      those reared under standard commercial practice. During 48 h posthatch, fed
      poults utilized yolk and exogenous feed to increase BW by 11 g. The small
      intestine increased from 3.8% of BW at hatch to 8.9% after 48 h. In contrast, BW
      in feed-deprived poults decreased by 10 g, whereas the small intestine increased
      slightly in weight and composed 4.5% of BW after 48 h. The number of cells per
      villus and the villus surface area increased dramatically posthatch in the
      duodenum but more slowly in the jejunum and ileum. Enterocyte width changed
      little, but length increased more than twofold in the duodenum and by
      approximately 50% in the jejunum and ileum by 6 d posthatch. Lack of access to
      feed depressed the rate of growth of villi and enterocyte length in all
      intestinal segments until 6 d posthatch. All intestinal epithelial cells were
      proliferating at hatch, which changed rapidly within 48 h posthatch, with
      proliferating cells becoming located mainly in the intestinal crypts where about
      half of the cells were proliferating. In feed-deprived poults, the decrease in
      the proportion of proliferating cells in the crypt was greater than that of fed
      poults; after refeeding, an increase in the rate of proliferation was observed in
      feed-deprived poults. Plasma concentrations of Na, glucose, triglycerides, and
      phospholipids were not affected by feed deprivation; however, nonesterified fatty
      acid concentrations were enhanced in feed-deprived poults, indicating a greater
      use of fatty acids for energy. Plasma triiodothyronine (T3) concentrations, which
      may mediate some of the intestinal effects of feed deprivation, were depressed in
      poults without access to feed.

PMID- 11469655
TI  - Tissue distribution of gossypol enantiomers in broilers fed various cottonseed
      meals.
AB  - Plasma and tissue concentrations of total, (+)- and (-)-gossypol were determined
      in broilers fed cottonseed meals (CSM) from eight oil mills (five expander
      solvent, two expeller, and one direct solvent). Free gossypol in the meals ranged
      from 0.033 to 0.180%, and total gossypol ranged from 0.974 to 1.459%. The (+)
      enantiomer of gossypol varied from 53.8 to 61.3% of total gossypol. Eight CSM
      diets containing 28% CSM and a soybean meal control diet were fed to 162 1-d-old
      male broiler chicks during a 3-wk starter period. Concentrations of free gossypol
      in the CSM diets ranged from 92 to 504 microg/g, and total gossypol ranged from
      2,626 to 4,085 microg/g. All diets were formulated with the same concentrations
      of digestible lysine and methionine and were fed ad libitum. At 21 d of age,
      there were no significant differences in body weights, feed conversions, or
      mortality of birds fed the CSM diets when compared to birds fed the soybean meal
      diet. Concentrations of (+)- and (-)-gossypol in plasma, liver, kidney, and
      muscle increased linearly as the level of free gossypol increased in the diets.
      Liver had the highest concentration of total gossypol (71.4 to 313.6 microg/g DM)
      followed by kidney (9.2 to 36.3 microg/g DM), plasma (3.0 to 14.6 microg/mL), and
      muscle (2.1 to 9.8 microg/g DM). The proportion of (-)-gossypol was higher in
      plasma (26.7%) and kidney (25.6%) than in muscle (19.1%) and liver (16.0%).
      Performance data from this study indicate CSM can be used successfully in chick
      starter diets at levels up to 28% when diets are formulated on a digestible amino
      acid basis.

PMID- 11469656
TI  - Male and female broiler responses to low and adequate dietary threonine on
      nitrogen and energy balance.
AB  - This study evaluated nitrogen and energy utilization by male and female broilers
      that were at 46 and 54 d of age fed diets deficient or adequate in threonine.
      Birds were reared in floor pens of an open-sided house and were provided diets
      that met NRC (1994) nutrient recommendations from placement until 6 wk of age. At
      42 d, 48 birds (24 per sex) were selected and individually penned in Petersime
      batteries and were given feeds that were formulated to contain 0.52 or 0.74%
      total threonine having 18% CP and 3,200 kcal ME/kg. Two 24-h excreta collection
      periods were conducted on Days 46 and 54 to assess nitrogen and energy recovery.
      Males receiving adequate threonine had an advantage in retention of nitrogen and
      recovery of AMEn over males consuming the low threonine diet. Utilization of
      nitrogen by females was similar at both threonine concentrations, and AMEn
      corresponded to the concentration recovered by males when threonine was adequate.
      Inadequate threonine appears to create conditions that reduce recovery of energy
      by male broilers.

PMID- 11469657
TI  - Metabolizable energy values and amino acid availability of vetch (Vicia sativa)
      and ervil (Vicia ervilia) seeds soaked in water and acetic acid.
AB  - In two experiments we evaluated the effect of water and acetic acid soaking on
      ME, apparent amino acid (AA) availability, and true AA availability of vetch (V)
      and ervil (E) seeds. In Experiment 1, the feedstuffs were untreated (U) V or
      coarsely ground V soaked in water (1:10, wt/vol) at 40 C for 72 h with a water
      change every 12 h (40WV), vetch soaked in 1% acetic acid for 24 h at 40 C (40AAV)
      or at room temperature (RTAAV), or dehulled soybean meal (SBM). In Experiment 2,
      E seeds were subjected to the same soaking methods, and the ingredients were UE,
      40WE, 40AAE, RTAAE, and SBM. Each feedstuff was precision-fed to five
      individually caged mature ISA Brown roosters. A group of five roosters was used
      to correct for metabolic and endogenous energy and amino acid losses. The AME,
      AMEn, TME, and TMEn of UV and UE (in parentheses) were 2,558 (2,663), 2,840
      (3,098), 3,026 (3,154), and 2,934 (3,176) kcal/kg DM, respectively, and were, in
      general, higher than those of SBM. The TMEn of V increased as a result of soaking
      in water or acetic acid, whereas that of E decreased in 40WE and RTAAE by 492 and
      920 kcal/kg DM, respectively (P < 0.05). The apparent availability of most
      essential amino acids in UV and UE was lower (P < 0.05) than that of SBM. Acetic
      acid soaking of V, irrespective of temperature, and E at 40 C resulted in
      apparent AA availability similar to that of SBM except for Met. The true AA
      availability of V treated or not, and that of E soaked at 40 C, were similar to
      that of SBM. Results indicated that UV and UE are energy rich ingredients but
      detrimental to amino acid availability. Soaking the seeds in acetic acid at room
      temperature and at 40 C improved the nutritional value of V and E, respectively.

PMID- 11469658
TI  - Furosemide does not facilitate pulmonary vasodilation in broilers during chronic
      or acute unilateral pulmonary arterial occlusion.
AB  - Furosemide (FURO) is a diuretic and a putative pulmonary vasodilator that, when
      added to broiler diets, previously has been shown to reduce the cumulative
      pulmonary hypertension syndrome (PHS) mortality induced by cold temperatures. The
      objective of the present study was to evaluate the influence of dietary FURO on
      the pulmonary vasculature in broilers undergoing chronic or acute unilateral
      pulmonary arterial occlusion. Broilers were fed a standard ration throughout the
      entire experiment (Control group) or the same ration supplemented with 0.015%
      (wt/wt) FURO from Day 14 to 42 (FURO group). In the present study chicks were
      chosen at random at 16 to 18 d of age to undergo sham surgery or a chronic
      unilateral pulmonary artery clamp (PAC) procedure. Diet and surgical treatments
      resulted in Control-Sham, FURO-Sham, Control-PAC, and FURO-PAC groups. The
      Control-PAC and FURO-PAC groups did not differ in body weight or right:total
      ventricular weight ratios (RV:TV). The postsurgical mortality, ascites mortality,
      and mortality due to other causes did not differ between the Control-PAC and FURO
      PAC groups. Plasma Na+ (P < or = 0.05) was lower in the FURO-Sham group than in
      the Control-Sham group. Broilers from the same hatch were fed Control or FURO
      diets and surgically prepared for acute unilateral pulmonary arterial occlusion
      by using a snare. Tightening of the snare triggered characteristic increases in
      pulmonary blood flow, pulmonary arterial pressure, and pulmonary vascular
      resistance. Across all of these variables, the Control and FURO groups did not
      differ during any sample interval. Dietary FURO did not affect body weight,
      hematocrit, or RV:TV. Dietary FURO at 0.015% (wt/wt) does not appear to influence
      the pulmonary vasculature in broilers, but it may prolong the survival of
      broilers during the pathophysiological progression of PHS.

PMID- 11469659
TI  - The effect of insulin-like growth factor analogs on turkey satellite cell and
      embryonic myoblast proliferation.
AB  - The effects of several human and chicken insulin-like growth factor (IGF) analogs
      on turkey satellite cell and embryonic myoblast proliferation were examined in
      serum-free medium. Similar rates of proliferation were observed when human or
      chicken IGF-I or IGF-II (13.1 nM) was administered to satellite cells. The
      biopotency of two analogs, which were modified to prevent interaction with IGF
      binding proteins, was also examined. Human Des(1-6)IGF-II was equipotent to
      native human and chicken IGF-II. However, the chicken LR3 IGF-I analog was
      significantly less active toward satellite cells and embryonic myoblasts compared
      with chicken IGF-I. Human [Leu27] IGF-II, an analog designed to have reduced
      affinity to the IGF Type I receptor but unaltered binding to IGF-binding
      proteins, had a diminished effect on cell proliferation. Examination of IGF
      receptor binding characteristics revealed that chicken LR3 IGF-I had reduced
      ability to compete with [125I]hIGF-I for binding to satellite cells or embryonic
      myoblasts compared with chicken IGF-I. The observed biological responses to IGF
      suggest that IGF-binding proteins have little effect on Type I IGF receptor
      action in these cell types in serum-free medium. The results also suggest that
      alterations of the IGF molecule to prevent interaction with binding proteins may
      also alter receptor binding affinity.

PMID- 11469660
TI  - Incubation temperature affects plasma insulin-like growth factors in embryos from
      selected lines of turkeys.
AB  - An experiment was conducted to test the hypothesis that incubator temperature may
      affect circulating insulin-like growth factors (IGF-I and IGF-II). In prior
      studies, growth of turkey embryos was altered by increasing incubator
      temperatures. Interestingly, the embryonic growth of a growth-selected line (F)
      was reduced, whereas embryos from an egg-production-selected line (E) did not
      alter embryonic growth but altered organogenesis. Growth of the F and E lines was
      altered experimentally in the current study by increasing incubator temperature
      from 36.8 to 37.2 C during the last 3 d of incubation. Embryonic blood samples
      were taken and analyzed for glucose, glucagon, IGF-I, and IGF-II concentrations.
      Increased incubator temperature elevated embryonic plasma glucose concentrations
      of all treatments compared to controls, which was accompanied by increased plasma
      glucagon concentration only in the E line embryos. Line and treatment interacted
      to affect IGF-I and IGF-II concentrations of embryo and hatchlings. Line E
      embryos increased IGF-I in response to the higher temperature, but controls did
      not; F embryos altered IGF-II in response to treatment, but controls did not.
      Alterations in IGF-I in E corresponded to growth responses, whereas IGF-II in F
      corresponded to metabolic responses. We concluded that changes in turkey embryo
      growth rates to incubator temperature involved changes in IGF-I. Additionally,
      IGF-II and glucagon are involved in intermediary metabolism during higher
      temperature exposure.

PMID- 11469661
TI  - Effects of presence of a blastoderm on albumen height and pH of broiler hatching
      eggs.
AB  - Two experiments were conducted to determine whether the presence of a blastoderm
      could affect albumen liquefaction of broiler hatching eggs prior to setting and
      during the initial stages of incubation. Eggs were stored for 0 to 3 d at 18 C
      and 75% RH. Albumen height and pH were measured after 0 or 2 h of incubation. In
      both experiments, albumen height was significantly lower in fertilized eggs
      compared with unfertilized eggs. The interaction of fertility with incubation
      time for albumen height in Experiment 1 was not significant (P < or = 0.10). In
      Experiment 1, albumen pH was significantly higher for fertilized eggs compared
      with unfertilized eggs (P < or = 0.01); the difference was similar but not
      significant in Experiment 2. The results suggest that the embryo contributes to
      albumen liquefaction and that ammonia production by the embryo may account for
      the effect.

PMID- 11469662
TI  - Evaporative cooling of ventral regions of the skin in heat-stressed laying hens.
AB  - Laying hens held in battery cages in naturally ventilated poultry houses in hot
      countries usually develop hyperthermia, which adversely affects their
      performance. The present means of cooling alleviate to some degree, but cannot
      eliminate, the stress imposed by heat. A new approach to cooling of laying hens
      was developed, based on wetting the skin and promoting evaporation of water from
      the ventral regions of the bird. The type of plumage in the ventral regions and
      the exposed skin of the apteria enable more efficient wetting than is possible
      with dorsal cooling. A ventral cooling regime, comprising an initial period of
      frequent wettings followed by intermittent wetting for 10 s every 30 min was able
      to maintain normothermia of laying hens subjected to a 10-h period of heat
      exposure. Dorsal cooling was less efficient; body temperature and respiration
      rate were higher and skin temperatures were lower than in ventrally cooled hens.
      During 10 d of heat exposure, ventrally cooled hens maintained egg weight and
      shell index (mg/cm2), whereas their food intake decreased moderately. In
      contrast, egg weight, shell index, and food intake all decreased markedly in
      uncooled or dorsally cooled hens. Transient alterations in plasma concentrations
      of corticosterone, progesterone, and estradiol were noted in uncooled and
      dorsally cooled hens but not in ventrally cooled hens. Results indicate that
      ventral cooling is an efficient method to alleviate heat stress in laying hens
      during summer. Successful implementation of ventral cooling in poultry houses
      will depend on optimal installation of sprinklers and on minimal wetting of
      manure.

PMID- 11469663
TI  - Association between weight gain, blood parameters, and thyroid hormones and the
      development of ascites syndrome in broiler chickens.
AB  - The present study examined the association between thyroid hormones and the
      development of ascites on one hand and the ability to predict ascites from growth
      rate and hematocrit on the other hand. Ascites syndrome was induced in broiler
      chickens in two trials by exposing the chicks to low ambient temperature (Ta) and
      by supplying a pellet form of diet. Weight gain, hematocrit, hemoglobin, and
      plasma thyroxin (T4) and triiodothyronine (T3) concentrations were measured
      weekly for each bird, and comparisons were made between birds that eventually
      died from ascites and those that did not. Mortality from ascites amounted to 24.3
      and 24.2% in Trials 1 and 2, respectively. Weight gain did not differ between
      ascitic and healthy chickens up to approximately 2 wk before death but was
      significantly lower in the ascitic broilers 1 to 2 wk before death. Hematocrit
      was significantly higher in broilers with ascites with the exception of ascitic
      broilers that died at the age of 7 wk (Trial 1). In ascitic broilers, T4 and T3
      concentrations declined significantly during the week of death. The present
      findings raise the question of whether the association between low levels of
      thyroid hormones and the development of ascites is one of the physiological
      responses in the syndrome cascade, or whether the failure to maintain thyroid
      hormones concentration is one of the triggers of the syndrome initiation. This
      question requires further investigation. It can be concluded that a high rate of
      weight gain is not always a good predictor of ascites development. Hematocrit and
      thyroid hormones can provide a good indication but only during the last week of
      life, and not in all cases. None of these parameters, however, can predict the
      development of ascites at an early age.

PMID- 11469664
TI  - Marked differences in the splanchnometry of farm-bred and wild red-legged
      partridges (Alectoris rufa L.).
AB  - Relative weights of heart, spleen, pancreas, and liver and the relative lengths
      of the small intestine and the cecum were taken from 40 farm-bred and 43 wild
      juvenile red-legged partridges (Alectoris rufa Linnaeus) in central Spain.
      Expressed as a ratio to head and body length, farm-bred partridges had lighter
      hearts (17% lighter), spleens (78%), and livers (29%) and shorter small
      intestines (15%) and cecae (20%), than wild birds of the same age. When expressed
      as a ratio to body weight, farm-bred juvenile red-legged partridges had lighter
      hearts (12%) and livers (23%) and shorter small intestines (9%) and cecae (12%)
      than wild partridges. Those differences might have been produced by diet
      differences (such as fiber-poor, high-energy feeds used on farms) and may affect
      the survival of farm-bred partridges after release.

PMID- 11469665
TI  - Descriptive sensory analysis of meat from broilers fed diets containing vitamin E
      or beta-carotene as antioxidants and different supplemental fats.
AB  - The objective of this study was to investigate the effects of dietary fat (lard,
      sunflower oil, and olive oil) and supplementation of alpha-tocopheryl acetate or
      beta-carotene on descriptive sensory changes in broiler leg meat as evaluated by
      a trained panel. Twenty-five descriptors were analyzed from chicken leg meat: 11
      in raw meat and 14 in cooked meat. Rancid values were very low, possibly because
      samples were consumed between 1 and 4 d after slaughter, which maybe insufficient
      time for oxidative processes to decrease meat sensory quality. However, samples
      supplemented with vitamin E showed lower rancidity levels, although the
      differences were only significant when compared to a beta-carotene diet, whereas
      the control treatment showed intermediate scores. Beta-carotene modified texture
      scores compared to the control diet, although the differences were only
      significant in initial juiciness and teeth adhesion compared to the vitamin E
      treatment and in tenderness compared to the control. In addition, juiciness and
      tenderness were positively correlated according to the principal component
      analysis of sensory attributes. The effect of dietary fat on analyzed attributes
      was lower than the effect of dietary antioxidant. The most important effect of
      fat type was on hardness of internal fat. Chickens whose diets were supplemented
      with lard had higher scored values than chickens whose diets were supplemented
      with vegetable oils. However, type of fat added to diet did not significantly
      influence rancidity values. These results indicate that an increase in the degree
      of unsaturation of fat in meat does not cause an increase in the oxidation levels
      detected by the panel under the conditions of short-term storage.

PMID- 11469666
TI  - Chemical method for determination of carbon dioxide content in egg yolk and egg
      albumen.
AB  - The safety, quality, and shelf life of shell eggs is a function of carbon dioxide
      content. A commercial process was recently developed for rapidly cooling shell
      eggs by using cryogenic CO2. The benefit of this new process over existing
      cooling processes is that the CO2 addition during cryogenic cooling provides
      additional safety and quality enhancements. In order for these benefits to be
      fully developed into a process that can be adopted by the egg industry, and thus
      realized by the consumer, the amount of CO2 absorbed by the egg during this
      process needs to be quantified. Because the albumen pH of rapidly cooled eggs was
      reduced to pH <6.5, existing titrametric methods were not adequate for
      determining CO2 content. They did not prevent CO2 loss during neutralization. A
      simple and accurate method for determining CO2 content in acidified egg albumen
      and yolk samples was developed. This method involves the liberation of CO2 from
      an acidified egg sample into a standardized, dilute sodium hydroxide solution
      inside a sealed jar. The egg sample and a small beaker containing the
      standardized sodium hydroxide solution are placed in a glass jar and sealed.
      Next, a concentrated acid phosphate solution is injected through a rubber septum
      in the cap of the jar onto the egg sample, while avoiding contact with the sodium
      hydroxide solution. The sample is then stored at 37 C for 24 h. During this
      storage period, the carbon dioxide is released from the egg sample and is
      absorbed into the sodium hydroxide solution. Afterwards, the dilute sodium
      hydroxide solution is removed and titrated to the phenolphthalein endpoint using
      a dilute, standardized hydrochloric acid solution. The amount of hydrochloric
      acid solution required for neutralization can be directly related to CO2 content
      in the sample.

PMID- 11469667
TI  - Physicochemical and microbiological properties of selected rice flour-based
      batters for fried chicken drumsticks.
AB  - Rice flour-based batter (RFBB) formulations for chicken drumstick coating were
      developed as an alternative for traditional wheat flour-based batter (WFBB).
      Physicochemical properties and storage stability of selected RFBB were evaluated
      and compared to WFBB. Batter pickup of RFBB formulated in combination with
      oxidized corn starch and methylcellulose (MC) was not significantly different
      from that of WFBB. In contrast, batters with only rice and corn flour (60:40%
      flour weight) exhibited significantly higher pickup. Rice flour batter with 15%
      oxidized corn starch had the lowest batter pickup. All RFBB exhibited (P < 0.05)
      lower oil absorption than WFBB. The TBA values of RFBB and WFBB increased (P <
      0.05) with increased frozen storage time at -40 C for 90 d. The RFBB with MC
      exhibited the lowest TBA values, whereas WFBB had the highest values.
      Microstructural analysis revealed that freezing caused structural deterioration
      of all batters, but the RFBB with MC exhibited less freezing tolerance than other
      samples. The total plate counts of immediately fried or frozen fried chicken
      stored for 90 d were less than 1 log cfu/g sample. The RFBB with 5% oxidized corn
      starch and MC can replace WFBB on fried drumsticks. Additionally, RFBB results in
      a healthier product due to lower fat absorption.

PMID- 11469668
TI  - Assessing the frequency and consequences of Salmonella enteritidis deposition on
      the egg yolk membrane.
AB  - The site of deposition of Salmonella enteritidis in eggs could influence the
      extent to which this pathogen multiplies before refrigeration achieves growth
      inhibiting internal temperatures. The first part of this study sought to
      determine whether S. enteritidis inoculated onto the exterior (vitelline)
      membrane surface of egg yolks was able to penetrate into and multiply within the
      yolk contents. When 10(2) cfu of S. enteritidis was inoculated onto the exterior
      surface of intact egg yolks, multiplication within the interior yolk contents
      occurred in 10% of samples after 6 h of incubation and in 75% of samples after 24
      h at 25 C (reaching mean levels of about 10(4) cfu/mL) but in only 20% of samples
      incubated for 72 h at 15 C. The second part of this study applied an oral
      infection model in laying hens to establish the relative proportions of
      contaminated eggs in which S. enteritidis deposition was associated with the yolk
      membrane or was found inside the yolk contents. Although approximately 4.3% of
      egg yolks were positive for S. enteritidis when both yolk contents and membranes
      were sampled, only about 0.5% of samples of yolk contents (without membranes)
      were positive. Although deposition of S. enteritidis within egg yolks appears to
      occur infrequently, rapid refrigeration of eggs is necessary to prevent the
      penetration of S. enteritidis into and multiplication within egg yolks.

PMID- 11469669
TI  - Diagnostic and therapeutic dilemmas in the management of pediatric-onset bipolar
      disorder.
AB  - Although the diagnosis of pediatric-onset bipolar disorder is controversial, an
      increasing literature of systematic research has challenged the traditional view
      that this disorder is a rare condition. This article summarizes research
      regarding the atypical presentation of pediatric bipolar disorder and its overlap
      with attention-deficit/hyperactivity disorder and other comorbid conditions, as
      well as family-genetic and treatment data. When structured interview data were
      examined, cases of pediatric mania constituted 16% of referrals to our outpatient
      clinic. Presentation is atypical by adult standards and includes irritability,
      chronicity, and mixed state. Family-genetic and treatment data help to establish
      diagnostic validity. Pediatric bipolar disorder is not a rare condition.
      Treatment requires a combined pharmacotherapy approach to address issues of
      comorbidity. Atypical antipsychotic medications have provided promising treatment
      results, but additional controlled clinical trials are needed.

PMID- 11469670
TI  - Major system toxicities and side effects of anticonvulsants.
AB  - The use of anticonvulsants is expanding in the treatment of bipolar and related
      disorders. Although they have characteristics in common, the anticonvulsants
      currently used are quite diverse and vary in their spectrum of activity, quality
      of supporting evidence, and organ toxicities. Common side effects of
      anticonvulsants that can limit tolerability but are not physiologically severe
      include sedation and other cognitive impairments, tremor, and gastrointestinal
      side effects. Possibly less common, but of more physiologic significance, are
      effects on body weight and metabolism and dose-related hepatic and hematologic
      effects. Severe, but rare, toxicities include skin, bone marrow, and hepatic
      toxicity due to hypersensitivity. The most important aspect of successful
      management of severe toxicities is early detection, discontinuation of the
      medicine, and vigorous treatment of the toxicity. Anticonvulsants can also be
      associated with fetal toxicity, especially neural tube defects. In general,
      anticonvulsants are well tolerated and their effectiveness greatly outweighs risk
      or annoyance from side effects, but side effects must be kept in mind when
      choosing and monitoring treatment.

PMID- 11469671
TI  - Cutaneous reactions to anticonvulsant medications.
AB  - Skin eruptions are an important consideration for any clinician who prescribes
      anticonvulsant medications. The timely recognition and accurate diagnosis of
      cutaneous reactions can prevent potentially fatal reactions and affect subsequent
      anticonvulsant treatment options. This review addresses the most common and most
      serious cutaneous reactions to anticonvulsant medications. The anticonvulsant
      hypersensitivity syndrome and individual antiepileptic medications that cause
      severe skin reactions will be reviewed. These reactions include morbilliform and
      urticarial drug eruptions as well as the erythema multiforme spectrum.

PMID- 11469672
TI  - Cognitive side effects of anticonvulsants.
AB  - The increasing use of anticonvulsant drugs in psychiatry has prompted greater
      awareness of their effects on a range of psychiatric domains, including
      cognition. Older versus newer antiepileptic drugs have been reported to either
      worsen or enhance cognitive performance in clinical populations, and the extent
      to which cognitive disturbances may reflect iatrogenic factors versus
      psychopathology is subject to debate. We review current information about the
      role of anticonvulsants in cognition, with particular emphasis on newer compounds
      (such as lamotrigine, gabapentin, and topiramate), the cognitive dimensions of
      affective illness, and the clinical approach to evaluating cognition in
      psychiatric patients taking anticonvulsant drugs over time.

PMID- 11469673
TI  - Introduction: the role of anticonvulsants as mood stabilizers.

PMID- 11469674
TI  - Bipolar rapid cycling: focus on depression as its hallmark.
AB  - The phenomenon of frequent cycling in bipolar disorder was first recognized by
      Emil Kraepelin in 1913. More recently, rapid cycling has been reported to be a
      predictor of nonresponse to treatment. At the time of presentation, most patients
      with DSM-IV-defined rapid cycling appear to be in the depressed phase of their
      illness. Frequent and more severe episodes of depression appear to be the
      hallmark of rapid cycling. Reported in this article are recent preliminary data
      suggesting that the combination of lithium and divalproex sodium administered
      continuously over 6 months appears to result in marked acute and continuation
      antimanic efficacy in 85% of patients and marked antidepressant efficacy in 60%.
      However, only one half of patients experienced bimodal stabilization. Comorbid
      alcohol, cannabis, and/or cocaine abuse and/or dependence did not appear to
      directly affect the spectrum of efficacy of lithium and divalproex or response
      rates in compliant patients. Comorbidity appeared to alter prognosis by
      increasing the prevalence of poor compliance. The majority of patients receiving
      lithium and divalproex who required additional treatment were depressed,
      suggesting that the frequent recurrence of depression is the primary unmet need
      in patients with rapid cycling. The use of antidepressants in this population has
      been discouraged because of concerns about the possibility of cycle acceleration.
      There exists a need for a pharmacotherapy that not only possesses marked acute
      antidepressant properties, but that does so without inducing switching or cycle
      acceleration. A double-blind, placebo-controlled trial of lamotrigine monotherapy
      in bipolar I depression has demonstrated efficacy without causing switching at a
      rate exceeding placebo; however, this initial study excluded patients with rapid
      cycling. To explore the efficacy of lamotrigine in rapid cycling, a recent
      multicenter study has examined lamotrigine as a maintenance therapy for this
      population. The results indicate that lamotrigine may be a useful treatment for
      patients with rapid-cycling bipolar II disorder and that this drug has begun to
      address this unmet need.

PMID- 11469675
TI  - Bipolar spectrum disorder: improving its recognition and diagnosis.
AB  - The lifetime prevalence of bipolar I disorder is approximately 1%. However, the
      prevalence of bipolar spectrum disorder is substantially higher. Bipolar spectrum
      disorder is a longitudinal diagnosis characterized by abnormal mood swings
      comprising some of the following cross-sectional clinical states: mania,
      hypomania, mixed states, hyperthymic temperament, major depressive episode, and
      depressive mixed state. Most bipolar spectrum patients present for treatment
      during a depressive episode, and therefore clinicians often miss the diagnosis of
      bipolar spectrum disorder. Several studies have documented that patients often
      wait as long as 10 years for the correct diagnosis of bipolar spectrum disorder.
      One way to increase recognition of bipolar spectrum disorder is to screen for it.
      A recently introduced screening instrument for bipolar spectrum disorder, the
      Mood Disorder Questionnaire, is described.

PMID- 11469676
TI  - The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and
      induces apoptosis in human solid tumors.
AB  - 2-Methoxyestradiol (2-ME) is a physiological metabolite of estrogen, which is
      excreted with the urine. In contrast to most estrogens, tumor growth-inhibiting
      effects were observed. Further studies have revealed that it may be an effective
      anticancer compound for many tumor types. Several different mechanisms have been
      attributed to 2-ME. Besides a strong antiangiogenic effect on endothelial cells
      and tumors, there is a tubulin-inhibiting mechanism, causing cells to arrest in
      the G2/ M phase of the cell cycle. In other tumors, p53-dependent and p53
      independent mechanisms with induction of apoptosis have been shown. The number of
      different tumors examined for a growth-inhibiting effect is increasing, and new
      mechanisms are continuously described. In vivo studies in mice, rats, and dogs
      show no or very little toxicity, even at high doses. Here, we discuss the
      antitumor activity and their mechanisms. 2-ME appears to be a new anti-tumor
      compound with strong potential for clinical application.

PMID- 11469677
TI  - Cyclooxygenase-2: a novel target for cancer chemotherapy?
AB  - Epidemiologic studies have documented a 40-50% reduction in incidence of
      colorectal cancer in individuals taking nonsteroidal antiinflammatory drugs
      (NSAIDs). Since NSAIDs are known to inhibit cyclooxygenases (COX-1, COX-2), the
      basic mechanism of their antitumor effects is conceivably the altered metabolism
      of arachidonic acid and, subsequently, prostaglandins (PGs). Although COX-2, the
      inducible isoform, is regularly expressed at low levels in colonic mucosa, its
      activity increases dramatically following mutation of the APC (adenomatous
      polyposis coli) gene suggesting that beta-catenin/T-cell factor mediated Wnt
      signaling activity may regulate COX-2 gene expression. In addition, hypoxic
      conditions and sodium butyrate exposure may also contribute to COX-2 gene
      transcription in human cancers. The development of selective COX-2 inhibitors has
      made it possible to further evaluate the role of COX-2 activity in colorectal
      carcinogenesis. To date, at least five mechanisms by which COX-2 contributes to
      tumorigenesis and the malignant phenotype of tumor cells have been identified,
      including: (1) inhibition of apoptosis; (2) increased angiogenesis; (3) increased
      invasiveness; (4) modulation of inflammation/immuno-suppression; and (5)
      conversion of procarcinogens to carcinogens. A clear positive correlation between
      COX-2 expression and inhibition of apoptosis has been established, associated
      with increased PGE2 levels resulting in modulation of pro- and anti-apoptotic
      factors (e.g., bcl-2, MAKs/ras, caspase-3, Par-4). In terms of angiogenesis and
      invasiveness, COX-2 activity was found to increase the expression of growth
      factors (e.g., VDEG, PDGF, bFGF) and matrix metalloproteinases (MMPs). Since COX
      2 inhibitors have been demonstrated to interfere with tumorigenesis and
      apoptosis, COX-2 and its gene product may be attractive targets for therapeutic
      and chemoprotective strategies in colorectal cancer patients. This may lead to
      new perspectives that by controlling the cancer phenotype, rather than attempting
      to eradicate all affected cells, may provide significant benefits to the cancer
      patient.

PMID- 11469678
TI  - Apoptosis induced in HepG2 cells by short exposure to millimolar concentrations
      of ethanol involves the Fas-receptor pathway.
AB  - PURPOSE: We previously found that ethanol-induced apoptosis is associated with an
      activation of caspase-3. However, the initial triggering of this process is yet
      unknown. Therefore, the present study was designed to determine whether the Fas
      receptor pathway plays a role in the initiation by ethanol of human
      hepatocellular carcinoma (HepG2) cell apoptosis. METHODS: HepG2 cells were
      incubated with or without 1 mM ethanol for 24 h. Apoptosis was assessed by DNA
      fragmentation and caspase-8 activity. Selective inhibitors of caspase-8 and
      caspase-9 were used to analyze the role of both caspases on apoptosis. Soluble
      human Fas ligand (Fas-L) was determined by enzyme-linked immunosorbent assay
      (ELISA). A fluorescent dye was used to investigate the permeability of the
      mitochondrial outer membrane. A recombinant Fas fusion protein was used to
      inhibit the activation of Fas receptors. Human anti-Fas-L antibody was employed
      to neutralize Fas-L released from the cells. RESULTS: Caspase-8 activity
      increased significantly threefold (P < 0.005) after 12 h incubation of HepG2
      cells with 1 mM ethanol whereas no change was observed in control cells.
      Incubation with caspase-8 inhibitor completely prevented apoptosis induced by
      ethanol (P < 0.001). In contrast, a caspase-9 inhibitor did not significantly
      reduce apoptosis. The permeability of the outer mitochondrial membrane was not
      altered. Neutralization of Fas-receptors by Fas fusion proteins completely
      attenuated ethanol-induced apoptosis in HepG2 cells treated with ethanol.
      CONCLUSIONS: These findings show that apoptosis induced by low concentrations of
      ethanol in human HepG2 cells is associated with Fas-receptor activation and
      subsequent caspase-8 activation. Triggering of apoptosis through Fas-receptors
      represents a mechanism of action different from that observed with high
      concentrations of ethanol.

PMID- 11469679
TI  - Modulation of VP-16 cytotoxicity by carboplatin and 41.8 degrees C hyperthermia.
AB  - PURPOSE: To study in vitro the effect of carboplatin and/or hyperthermia in
      relation to etoposide (VP-16) cytotoxicity in L929 cells. METHODOLOGY/RESULTS:
      Cell survival assays demonstrated that the addition of 41.8 degrees C (x60 min)
      hyperthermia and carboplatin to VP-16 produced an antagonistic effect relative to
      VP-16 cytotoxicity in L929 cells; administering carboplatin and hyperthermia 24 h
      before VP-16 reduced this drug resistance; administering carboplatin and
      hyperthermia 48 h before VP-16, however, produced a supra-additive cytotoxicity.
      In order to gain insight into the molecular basis for these observations, we
      investigated the effect of hyperthermia and/or carboplatin on the stress protein
      GRP78, which is known to affect VP-16 cytotoxicity. Results obtained were
      consistent with the hypothesis that carboplatin and hyperthermia perturbation of
      NAD + pools results in down-regulation of GRP78 with subsequent modulation of VP
      16 cytotoxicity. To further explicate these results we studied G-361 as a control
      cell line that had significantly higher pretreatment NAD+ levels, which were not
      affected by carboplatin and/or hyperthermia. This cell line did not exhibit a
      down-regulation of GRP78 or modulation of VP-16 cytotoxicity as a function of
      carboplatin and hyperthermia. CONCLUSIONS: These data taken collectively,
      demonstrate a sequence effect (regarding the aforementioned antineoplastic
      agents), and provide a framework for future studies directed at the therapeutic
      optimization of the sequential application of carboplatin, hyperthermia, and VP
      16.

PMID- 11469681
TI  - Comparisons of cancer detection rate and costs of one cancer detected among
      different age-cohorts in immunochemical occult blood screening.
AB  - PURPOSE: This study was carried out to compare the detection rate for colorectal
      cancer and the average costs to detect one patient with colorectal cancer among
      three different age-cohorts in immunochemical occult blood screening by OC
      Hemodia. METHODS: In a population-screening program, 17,432 subjects received an
      immunochemical fecal occult blood test. In a medical checkup for colorectal
      cancer 7,232 subjects received colonoscopy. They were divided into three groups
      according to their ages: younger (4,049 years); middle (50-59); and older (60+)
      groups. The detection rate for colorectal cancer and the average costs to detect
      one patient with colorectal cancer were evaluated among the three groups.
      RESULTS: In the screening program-based study, the cancer detection rate and the
      average costs for one colorectal cancer detected were calculated as 0.09% and
      $13,352, 0.28% and $4,555, 0.29% and $4,461 for the younger, middle, and older
      groups, respectively. In addition, in the medical checkup-based study, the
      detection rate and the average costs were calculated as 0.3% and $6,851, 1.5% and
      $1,517, 1.7% and $1,391 for the younger, middle, and older groups, respectively.
      In these two studies, the cancer detection rates were significantly different
      between the younger and middle groups (P < 0.05), and between the younger and
      older groups (P < 0.05). CONCLUSIONS: These findings indicate that the subjects
      aged under 50 have some disadvantage when carrying out the immunochemical fecal
      occult blood test--OC-Hemodia for colorectal cancer screening--from the viewpoint
      of screening efficiency as well as cost-effectiveness.

PMID- 11469680
TI  - Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse
      intestinal crypt cells.
AB  - PURPOSE: In this study we investigated the effect of Taxol, radiation, or Taxol
      plus radiation on highly proliferative normal tissue--the intestinal crypt cells
      of Swiss albino mice. MATERIALS AND METHODS: Swiss-albino mice, 3-4 months old,
      were used in this study. Taxol was administered by bolus intravenously through
      the tail vein. Radiation was given using a linear accelerator. There were four
      treatment categories, which comprised a total of 34 groups. Each group consisted
      of five animals. The first category was a control category which comprised one
      group (n = 5). The second treatment category was Taxol alone which comprised
      three groups (n = 15). The third treatment category was radiation alone which
      comprised three groups (n = 15). The fourth treatment category was Taxol plus
      radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol
      or radiation or combined administration using ether anesthesia. Using a light
      microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of
      mice that were stained with hematoxylin-eosin. Differences between groups were
      statistically evaluated with Student's t-test. RESULTS: Taxol caused a dose
      dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P =
      0.006) at high doses. Similarly, radiation caused a dose-dependent increase in
      apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher
      radiation doses. Compared to radiation alone, Taxol caused a significant
      induction of apoptosis (P = 0.010). In combination, no significant
      radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when
      compared to radiation alone. However, an increase in apoptosis was observed after
      24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001
      and P = 0.0001). CONCLUSION: These findings suggest that Taxol did not cause a
      radiosensitizing effect in intestinal crypt cells. However, a 24-hour
      pretreatment of Taxol exposure followed by radiation caused significant induction
      of apoptosis and reduction of the mitotic index when compared to other Taxol
      timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these
      proliferative cells may be due to enhanced mitotic death rather than apoptotic
      death.

PMID- 11469682
TI  - Protective effect of oral phosphatidylcholine on radiation-induced release of
      intestinal peptidases in rats.
AB  - PURPOSE: To investigate whether phosphatidylcholine (PPC) has a protective effect
      on mucosa-irradiated rats. METHODS: The rats were orally fed with 25, 50, and 100
      mg PPC/kg body weight (b.w.), respectively, for 3 weeks before irradiation. After
      administering the medication and 1 day after irradiation, a 20 cm segment of the
      proximal jejunum was perfused in situ and peptidase activities, as well as the
      concentrations of the membrane components, were assayed. RESULTS: We have shown
      that the application of a low dose of 25 mg PPC/kg b.w. daily for 21 days can
      prevent damage to membranes induced by 2.0 Gy as represented in the peptidase
      release profiles during the perfusion of the proximal jejunum of rats. Higher
      dose levels did not increase the protective effect. CONCLUSIONS: These findings
      suggest that a low dosage of exogenous PPC is capable of hindering the impairment
      of membranes induced by a small dose of radiation.

PMID- 11469683
TI  - Induction and expression of cyclin D3 in human pancreatic cancer.
AB  - PURPOSE: Cyclins play a key role in the control and regulation of the cell cycle.
      The role of cyclins in the pathogenesis of pancreatic cancer is largely unknown.
      METHODS: Using Northern blot analysis, polymerase chain reaction (PCR) and
      immunohistochemistry, we examined the expression of cyclins D1, D2, and D3 in
      human pancreatic cancer and studied the induction of these cyclins by growth
      factors in pancreatic cancer cell lines. RESULTS: We now report that cyclin D1
      and D3 mRNAs are expressed in human pancreatic cancer cell lines, and that the
      expression of cyclin D3 is enhanced in pancreatic cancer cells by amphiregulin, a
      member of the epidermal growth factor family. Cyclins D1 and D3 are also
      expressed in normal and malignant pancreatic tissues. However, while the normal
      pancreas and pancreatic cancers express cyclin D2 as determined by reverse
      transcriptase PCR, we could not detect cyclin D2 mRNA by either Northern blot
      analysis or reverse transcriptase PCR in the two pancreatic cancer cell lines.
      Immunohistochemical analysis revealed the expression of cyclin D3 in pancreatic
      cancer cells. CONCLUSIONS: These findings suggest that D-type cyclins are
      differentially expressed in pancreatic cancer and that the aberrant activation of
      the EGF receptor in human pancreatic cancer by amphiregulin may lead to the
      progression of the cell cycle via induction of cyclin D3 expression, thus
      contributing to the growth advantage of these transformed cells.

PMID- 11469684
TI  - Matched pair analysis of survival after chest-wall recurrence compared to mammary
      recurrence: a long-term follow up.
AB  - BACKGROUND: Local recurrence remains a major concern after primary treatment of
      breast cancer and has a major impact on subsequent survival. While most studies
      report a poorer survival rate in patients with a local recurrence after
      mastectomy than after breast conservation, it remains controversial whether
      different risk profiles at the time of primary diagnosis may account for this
      difference. METHOD: Matched pair analysis of 134 patients with newly diagnosed
      locoregional recurrence of breast cancer without evidence of systemic disease.
      Matching criteria included the primary surgical treatment, tumor size, nodal
      status, and age. The significance of various prognostic parameters at the time of
      primary diagnosis and at the time of recurrence were evaluated, by univariate and
      multivariate analyses, with respect to survival after recurrence. The median
      follow-up was 8.4 years. RESULTS: Risk factors at the time of presentation, such
      as tumor size and lymph node status, were comparable between both groups. Local
      recurrence occurred on an average 9 months earlier in patients after mastectomy
      (P = 0.08). Univariate analysis showed that lymph node status (P = 0.0001) and
      disease-free interval from primary treatment to local recurrence (P = 0.0002)
      were the most significant single prognostic factors for subsequent survival after
      local recurrence. The primary surgical treatment modality was shown to be of
      marginal statistical influence (only P = 0.05). CONCLUSION: Local recurrence
      after mastectomy seems to be associated with worse survival than after breast
      conserving therapy. Early onset of chest-wall recurrence, moreover, represents
      the highest independent risk for cancer-associated death.

PMID- 11469685
TI  - Serous tumors of low malignant potential of the ovary-molecular pathology: part
      2.
AB  - A progressive development from serous tumors of low malignant potential (SLMP) to
      bluntly invasive serous carcinoma has been suggested in parallel to the concept
      of adenoma-carcinoma sequence in colorectal carcinomas. However, recent genetic
      data enforces a reassessment of the concept that SLMP tumors represent precursor
      lesions to invasive serous carcinoma. Despite the benign nature of the majority
      of these tumors, some will behave worse. The identification of those SLMP tumors
      with an aggressive clinical behavior remains difficult, regardless of a growing
      body of molecular pathologic investigations. Expression of p53, c-erbB2, as well
      as the presence of ras mutations are not helpful in this respect. Immunostaining
      of both MMP-2 and basement membrane components such as collagen type IV, as well
      as the disintegration of collagen type I at the tumor-host interface, may be
      helpful for the diagnosis of a microinvasive SLMP, but it remains questionable
      whether this is important for prognosis. The differential diagnosis to frankly
      invasive carcinoma depends on the detection of destructive stromal invasion. In
      questionable cases, the loss of N-cadherin would argue for the presence of a
      carcinoma whereas the coexpression of p21 and MDM2 is rather characteristic for
      SLMP tumors.

PMID- 11469686
TI  - Lymphoepithelioma-like carcinoma of the urinary bladder: a clinicopathologic
      study of 13 cases.
AB  - Lymphoepithelioma-like carcinoma (LELCA) of the urinary bladder is a rare variant
      of bladder cancer characterized by a malignant epithelial component densely
      infiltrated by lymphoid cells. It is characterized by indistinct cytoplasmic
      borders and a syncytial growth pattern. These neoplasms deserve recognition and
      attention, chiefly because they may be responsive to chemotherapy. We report on
      the clinicopathologic features of 13 cases of LELCA recorded since 1981. The
      chief complaint in all 13 patients was hematuria. Their ages ranged from 58 years
      to 82 years. All tumors were muscle invasive. A significant lymphocytic reaction
      was present in all of these tumors. There were three pure LELCA and six
      predominant LELCA with a concurrent transitional cell carcinoma (TCC). The
      remainder four cases had a focal LELCA component admixed with TCC.
      Immunohistochemistry showed LELCA to be reactive against epithelial membrane
      antigen and several cytokeratins (CKs; AE1/AE3, AE1, AE3, CK7, and CK8). CK20 and
      CD44v6 stained focally. The lymphocytic component was composed of a mixture of T
      and B cells intermingled with some dendritic cells and histiocytes. Latent
      membrane protein 1 (LMP1) immunostaining and in situ hybridization for Epstein
      Barr virus were negative in all 13 cases. DNA ploidy of these tumors gave DNA
      histograms with diploid peaks (n=7) or non-diploid peaks (aneuploid or
      tetraploid; n=6). All patients with pure and 66% with predominant LELCA were
      alive, while all patients having focal LELCA died of disease. Our data suggest
      that pure and predominant LELCA of the bladder appear to be morphologically and
      clinically different from other bladder (undifferentiated and poorly
      differentiated conventional TCC) carcinomas and should be recognized as separate
      clinicopathological variants of TCC with heavy lymphocytic reaction relevant in
      patient management.

PMID- 11469687
TI  - In situ characterization of human cytomegalovirus infection of bronchiolar cells
      in human transplanted lung.
AB  - Distal airway cell infection by human cytomegalovirus (HCMV) in transplanted lung
      has been occasionally reported but not systematically investigated. The present
      study aimed at testing the prevalence of HCMV bronchiolar infection in human
      transplanted lung. We identified and immunophenotyped, with double labeling,
      infected lung cells in 31 transbronchial biopsies with HCMV infection, containing
      distal airways (7 HCMV pneumonias, 7 HCMV infection without inflammation, and 17
      morphologically occult, non-cytopathic HCMV infection). HCMV-infected cells in
      pneumonias, localizations, and occult infections were alveolar epithelia (32.8%,
      42.8%, and 53.5%, respectively), endothelia (22.9%, 24.7%, and 26.4%,
      respectively), macrophages (0.006%, none, and none, respectively), airway
      epithelia (0.01%, 8.9%, and none, respectively), and bronchiolar smooth muscle
      cells (0.011%, 14.6%, and 16.1%, respectively). Ciliated and bronchiolar smooth
      muscle cells in transplanted lung only occasionally harbored viral infection and
      never showed viral cytopathy. On the basis of our morphological observations,
      HCMV infection of bronchiolar wall cells is rare, while alveolar epithelia and
      capillary endothelial cells are the major targets of lung infection.

PMID- 11469688
TI  - Expression of a glypican-related 62-kDa antigen is decreased in hepatocellular
      carcinoma in correspondence to the grade of tumor differentiation.
AB  - A monoclonal mouse antibody, Be-F4, was generated by means of immunization with a
      synthetic oligopeptide. In Western blots, this antibody recognizes an antigen
      with an apparent molecular mass of 62 kDa, termed p62. Immunohistochemical
      analysis of p62 in hepatocellular carcinoma (HCC) specimens (n=33) and in
      corresponding non-cancerous liver tissue was performed using monoclonal antibody
      Be-F4. All non-neoplastic hepatic cells showed, without exception, a moderate or
      strong staining intensity of the 62-kDa antigen, recognized by Be-F4. In contrast
      to the non-neoplastic hepatocytes, the cellular p62 content was unambiguously
      reduced in all malignant cells. The extent of decrease of p62 corresponded to the
      grade of histological differentiation of HCC cells (P<0.001). Using a
      semiquantitative scoring system, the median of p62 expression, which was 2.1 for
      normal hepatocytes, was significantly reduced to 1.2 for G1, 1.0 for G2, and 0.2
      for G3 HCCs. These data suggest that neoplastic transformation is associated with
      a reduced p62 content.

PMID- 11469689
TI  - The formation of capsule and septum in human hepatocellular carcinoma.
AB  - The formation of fibrous capsule around the cancer nodule and of the septum in
      the tumor is frequently observed with the development of hepatocellular carcinoma
      (HCC). We aimed to clarify how the capsule and septum were formed during the
      growth of HCC. Liver samples surgically resected from 25 patients with HCC were
      studied with in situ hybridization for type-I, -III, and -IV procollagen. Type-I
      and -III procollagen-expressing cells, mostly alpha-smooth muscle actin (SMA)
      positive, were increased in the fibrous capsule and in the septum between HCC
      nodules. These cells were also found at the invasion front of HCC and around the
      necrotic cancer tissues. Type-IV procollagen gene expression was mainly observed
      in mesenchymal cells localized in both HCCs and non-cancerous liver. Cancer cells
      or hepatocytes did not express any of these procollagen genes. The present study
      reveals that the capsule and septum are mainly formed by alpha-SMA-positive
      mesenchymal cells at the interface between two different tissues (e.g., cancer
      nodule vs non-cancerous liver or another cancer nodule). The wound healing occurs
      even in HCC. The capsule formation may result from interaction between tumor and
      host liver and interfere the growth and invasion of HCC.

PMID- 11469690
TI  - Immortalized bovine pancreatic duct cells become tumorigenic after transfection
      with mutant k-ras.
AB  - Mutation of the K-ras gene is thought to be an early and important event in
      pancreatic carcinogenesis. In order to study the role of this molecular
      alteration in the transition from the normal to the neoplastic pancreatic cell,
      bovine pancreatic duct cells were first immortalized by SV40 large T antigen (Ag)
      complementary (c)DNA transfection and then transfected with a mutated K-ras gene.
      As did primary duct cells, the immortalized duct cells (more than 100 passages)
      expressed cytokeratins, carbonic anhydrase type-II, cystic fibrosis transmembrane
      conductance regulator (CFTR), and multidrug resistance (mdr). They grew as a
      single layer after transplantation under plastic domes and formed three
      dimensional structures resembling ducts when grown on Matrigel. Cell growth was
      stimulated by insulin, epidermal growth factor (EGF), transforming growth factor
      (TGF)-alpha, but cells did not respond to gastrin and CCK-8. They did not form
      colonies in soft agar nor did they form tumors in nude mice. Immortalized cells
      transfected with mutated K-ras acquired the ability to form tumors after
      orthotopic injection into the nude mouse pancreas. It is concluded that SV 40
      immortalized bovine pancreatic

PMID- 11469691
TI  - Tissue macroarrays ("microchops") for gene expression analysis.
AB  - We describe a simple system of tissue arraying with multiple tissue fragments
      obtained with a biopsy punch from selected areas of paraffin blocks. The new
      blocks thus constructed allow multiple tissue sections in which the uniform shape
      of the fragments coupled with a geometrical display and a significant amount of
      tissue per case allows a dependable, cost-effective way to screen tumors or other
      kinds of tissues with techniques such as immunohistochemistry. This system avoids
      the disadvantages of previous laborious methods of tissue arraying, such as
      expensive equipment and scarce tissue sampling, and it can be implemented in any
      institution with minimal cost and elaboration.

PMID- 11469692
TI  - Microvessel density in pituitary adenomas and carcinomas.
AB  - Tumor growth depends on several factors, including angiogenesis. Tumors cannot
      grow if new vessels are not formed to supply the cells with oxygen and other
      nutrients and to remove waste products. Increased angiogenesis can be correlated
      with tumor growth and metastatic potential in many tumor types, indicating that
      neoformation of vessels is a prognostic indicator of tumor behavior. We evaluated
      microvessel densities in 157 various pituitary adenoma types and seven pituitary
      carcinomas using immunocytochemistry for CD-34 antigen, a reliable marker of
      endothelial cells. The lowest percentage of microvessel density was found in
      growth hormone-producing adenomas, the highest level in pituitary carcinomas. In
      general, no major correlation was found between MIB-1 index (an indicator of cell
      proliferation) and microvessel density. The statistical study also demonstrated
      no gender-dependent changes in the microvessel density of pituitary tumors.
      Although the microvessel density was not significantly different in relation to
      invasiveness of pituitary tumors, our results demonstrate a tendency of invasive
      pituitary tumors to be more highly vascularized than non-invasive ones. Dopamine
      agonist and long-acting somatostatin analog treatment compared with untreated
      tumors did not significantly affect microvessel densities. Statistical
      differences were demonstrated in the microvessel density of macroadenomas between
      patients older and patients younger than 40 years. Significant differences were
      also apparent in the microvessel densities between microadenomas and
      macroadenomas diagnosed in young patients but not in the older age group. The
      strongly positive correlation observed between microvessel density and age is
      consistent with the view that age of the host may have an influence on the extent
      of neovascularization of pituitary adenomas.

PMID- 11469693
TI  - Morphometric microvascular characteristics predict prognosis in superficial and
      invasive bladder cancer.
AB  - Recent research has shown that neovascularization, quantitated by microvessel
      density (MVD), constitutes a strong prognostic indicator in patients with
      invasive urothelial carcinomas. These studies, however, have focused only on MVD
      as the only factor reflecting angiogenesis in transitional-cell carcinomas
      (TCCs). The objective of this report was to evaluate multiple morphometric
      microvascular characteristics besides MVD in superficial and muscle-invasive TCCs
      separately, to provide a better approach to the relationship between
      angiogenesis, clinicopathological parameters, and prognosis. Histologic sections
      from 115 TCCs [35 superficial (T1) and 80 muscle-invasive] were immunostained for
      CD31 and evaluated using image analysis for the quantitation of MVD, area, total
      vascular area, major axis length, minor axis length, perimeter, compactness,
      shape factor, and Feret diameter. Patients were followed-up until death (n=31) or
      for an average of 42.2 months (median 38.5 months). MVD increased with
      progressing T category (P=0.049) but area (P=0.033), major axis length (P=0.022),
      perimeter (P=0.043), and Feret diameter (P=0.042) were highest in T2 tumors. Area
      was the single independent predictor of adverse significance in T1 TCCs, whereas
      for muscle-invasive tumors, survival was independently predicted by MVD.
      Regarding disease-free survival in superficial tumors, the single significant
      independent parameter was compactness, whereas area was an independent favorable
      indicator of disease-free survival for patients with invasive TCCs. It is
      concluded that the prognostic significance of neovascularization is better
      assessed by area and shape-related morphometric characteristics, whereas MVD
      becomes influential only with regard to overall survival of patients with
      invasive tumors.

PMID- 11469694
TI  - Localization and expression of osteopontin in the rotator cuff tendons in
      patients with calcifying tendinitis.
AB  - Calcifying tendinitis of rotator cuff tendons is a common and painful condition
      caused by ectopic calcification in humans. To examine the involvement of
      osteopontin (OPN), a potent regulator of calcium deposition on connective
      tissues, localization and expression of OPN protein and messenger (m)RNA were
      investigated in human tissue samples of calcified rotator cuff tendons.
      Immunohistochemistry demonstrated that OPN was localized in cells surrounding the
      calcified area. OPN was localized in two distinct cell types, i.e., fibroblast
      like cells negative for CD68 and tartrate-resistant acid phosphatase (TRAP) and
      multinucleated macrophages positive for CD68 and TRAP. In situ hybridization
      revealed that the mRNA expression of OPN in these cells coincided with the
      immunohistochemistry results, and these results were supported by reverse
      transcriptase polymerase chain reaction analysis using human OPN-specific
      oligonucleotides. Cells located away from the calcified area did not express OPN.
      The present findings indicate the involvement of OPN in the process of
      calcification of rotator cuff tendons and suggest that OPN plays a role in such
      painful disorders through the actions of at least two cell types.

PMID- 11469695
TI  - The juxtaglomerular apparatus in young type-1 diabetic patients with
      microalbuminuria. Effect of antihypertensive treatment.
AB  - BACKGROUND: Our goal was to investigate the effect of antihypertensive drugs on
      the juxtaglomerular apparatus (JGA) in young type-1 diabetic patients with
      microalbuminuria. METHODS: Twelve patients were allocated to treatment with
      either an angiotensin-converting enzyme inhibitor (group 1, six subjects) or a
      beta-receptor blocker (group 2, six subjects). A comparable group of nine
      patients without antihypertensive treatment provided reference values (group 3,
      nine subjects). Renal biopsies were taken at baseline and after a median of 40
      months (groups 1 and 2) and 30 months (group 3). Using light microscopy with
      1microm serial sections of the plastic-embedded biopsies, volumes of the JGA and
      glomerulus and areas of the macula densa and lumina of the afferent and efferent
      arterioles were obtained. RESULTS: A significant decrease of the volume of the
      JGA (P=0.026) and of the volume of the JGA relative to that of its corresponding
      glomerulus (P=0.0005) was noted in the reference group only. Negative
      correlations existed between the increase in the luminal area of the afferent
      arteriole and mean diastolic blood pressure in the study period in group 1
      (P=0.024) and group 2 (P=0.032). CONCLUSIONS: Our results showed that a decrease
      in the size of the JGA is offset by antihypertensives. The negative correlation
      between the change in the luminal area of the afferent arteriole and mean
      diastolic blood pressure in groups 1 and 2 suggest that renal protection in
      antihypertensive treatment may be through a better constriction of the afferent
      arteriole protecting the glomerulus from systemic blood pressure.

PMID- 11469696
TI  - Insulinoma of the pancreas with insular-ductular differentiation in its liver
      metastasis--indication of a common stem-cell origin of the exocrine and endocrine
      components.
AB  - We describe an insulinoma of the pancreas in a 56-year-old patient, which showed
      insular-ductular differentiation in its liver metastasis. Although the primary
      tumor was uniformly endocrine in nature with insulin production, the metastasis
      contained two distinct cell types in organoid arrangement. One cell type was
      insulin-positive and was arranged in islet-like structures; the other was insulin
      negative but distinctly pan-cytokeratin and cytokeratin 7 positive and arranged
      in ducts. In the primary tumor and the metastasis, the tumor cells were
      surrounded by a desmoplastic stroma. As to the histogenesis of the tumor and its
      metastasis, we discuss the following possibilities: (1) the tumor cells might
      derive from a common stem cell that matures into two phenotypically different
      cell lines, resembling the situation in embryogenesis and (2) one tumor cell type
      originates from the other by transdifferentiation (metaplasia). We conclude that
      the parallel occurrence of endocrine and ductal differentiation supports the
      concept that, under certain conditions, islet cells and ductular cells may also
      originate from islets and that mixed endocrine/exocrine pancreatic tumors do not
      necessarily arise from totipotent duct cells but might also have a primary
      endocrine cell origin.

PMID- 11469697
TI  - Inflammatory pseudotumor of the spleen.

PMID- 11469698
TI  - Gastrointestinal pacemaker cell tumour.

PMID- 11469699
TI  - Cardiac fibroma. A case presentation.

PMID- 11469700
TI  - New techniques for the evaluation of diabetic neuropathies.

PMID- 11469701
TI  - Chronic intermittent intravenous insulin therapy: a new frontier in diabetes
      therapy.
AB  - The limited success achieved in controlling diabetes and its complications with
      conventional insulin therapy suggests the need for reevaluation of the
      appropriateness of insulin administration protocols. Indeed, conventional
      subcutaneous insulin administration produces slowly changing blood insulin levels
      and suboptimal hepatocyte insulinization resulting in impaired hepatic capacity
      for processing incoming dietary glucose. The novel approach to insulin
      administration known as chronic intermittent intravenous insulin therapy (CIIIT)
      delivers insulin in a pulsatile fashion and achieves physiological insulin
      concentration in the portal vein. Done as a weekly outpatient procedure combined
      with daily intensive subcutaneous insulin therapy, this procedure has been shown
      to (1) significantly improve glycemic control while decreasing the incidence of
      hypoglycemic events, (2) improve hypertension control, (3) slow the progression
      of overt diabetic nephropathy, and (4) reverse some manifestations of diabetic
      autonomic neuropathy (e.g., abnormal circadian blood pressure pattern, severe
      postural hypotension, and hypoglycemia unawareness).

PMID- 11469702
TI  - Chronic intermittent intravenous insulin therapy: really a new therapeutic
      option?

PMID- 11469703
TI  - Re: Diabetes technology & therapeutics, 2000; 2:49-56.

PMID- 11469704
TI  - MiniMed headquarters celebrates grand opening.

PMID- 11469705
TI  - Utility of the AIDA diabetes simulator as an interactive educational teaching
      tool for general practitioners (primary care physicians).
AB  - In previous "Diabetes Information Technology & WebWatch" columns, various user
      experience with an interactive educational "virtual diabetes patient" simulator
      called AIDA have been documented. The simulator is available free of charge from
      http://www.2aida.org on the Web, and user comments that have been received to
      date about the program have highlighted some of the many and varied ways in which
      a range of people have been applying the diabetes simulations in their own
      particular situations and practices. Inevitably, up to now, a great deal of
      attention has focused on use by individuals with diabetes and their relatives, as
      well as by health-care professionals such as diabetologists/endocrinologists and
      diabetes educators. However, an important group of health-carers involved in the
      provision of day-to-day care for many people with diabetes are primary care
      physicians (general practitioners). The current "Diabetes Information Technology
      & WebWatch" column addresses this area, overviewing a workshop which was held in
      September 2000 in Italy to gain experience with application of the AIDA diabetes
      simulation approach as a teaching tool for general practitioners (GPs). Feedback
      obtained from participants attending the workshop was very positive, with GPs
      reporting the simulation approach to be both of interest and use. Further
      workshops involving other healthcare professionals--in particular, nurses--are
      planned.

PMID- 11469706
TI  - Skin biopsy as a tool to assess distal small fiber innervation in diabetic
      neuropathy.

PMID- 11469707
TI  - Methods for evaluation of peripheral neurovascular dysfunction.
AB  - Measurement of skin blood flow is a sensitive marker of C-fiber neurovascular
      dysfunction. It precedes development of abnormalities in diabetes mellitus,
      correlates with in vivo indices of the metabolic syndrome, and may be a
      "benchmark" for future studies on agents to improve microvascular dysfunction in
      diabetes mellitus. Skin blood flow can be measured under basal and stimulated
      conditions. There are different methods of evaluation. Iontophoresis and
      microdialysis are novel methods of drug delivery and the latter may be used as a
      means of extracting analytes in the skin. Theses methods are not invasive
      (iontophoresis) or minimally invasive (microdialysis). They can be performed
      repeatedly and safely in most patients. The use of microdialysis may be limited
      by sampling only water-soluble molecules. An alternative to microdialysis is
      iontophoresis, which works better with polar molecules. A combination of
      microdialysis and iontophoresis techniques can be useful in assessment of the
      pharmacokinetics of polar and nonpolar agents and the physiology and
      pathophysiology of the skin neurovascular system.

PMID- 11469708
TI  - Electrogastrography: physiological basis and clinical application in diabetic
      gastropathy.
AB  - Electrogastrography is the recording and measurement of gastric myoelectrical
      activity from electrodes placed on the surface of the epigastrium. Normal
      electrogastrograms (EGGs) reflect 3 cycles per min (cpm) gastric myoelectrical
      activity produced by specialized pacemaker cells, the interstitial cells of
      Cajal, located in the muscular wall of the gastric corpus and antrum. Gastric
      dysrhythmias (tachygastrias and bradygastrias) are disturbances of the normal
      gastric pacesetter potentials and are associated with symptoms of nausea,
      epigastric fullness, and bloating and with hyperglycemia and delayed gastric
      emptying. In diabetic gastropathy, the normal 3-cpm electrical rhythm is replaced
      with bradygastrias, tachygastrias, and mixed or nonspecific dysrhythmias.
      Diagnosis of gastric dysrhythmias identifies an objective neuromuscular
      abnormality in diabetic patients with upper gastrointestinal (GI) symptoms.
      Correction of gastric dysrhythmias decreases upper GI symptoms and may improve
      gastric emptying all of which may enhance glucose control. The EGG diagnosis of
      gastric dysrhythmias provides new insights into gastric neuromuscular
      abnormalities and guides therapies to improve upper GI symptoms in patients with
      diabetes mellitus.

PMID- 11469709
TI  - Heart rate variability measurement in diabetic neuropathy: review of methods.
AB  - Heart rate variability (HRV) is an important tool to analyze the autonomic
      function. It therefore has a special interest for early detection and ensuing
      treatment of autonomic neuropathy in diabetic patients. The aim of this work is
      to present a brief historical review of HRV, as well as a technical review of the
      most common methods to measure it. In this work is presented a system that
      performs three measurements of HRV. An overview of methodologies developed to
      quantify HRV is presented; this technical review covers the most common time and
      frequency domain techniques, for short and long periods of time, with comments
      about clinical utility of these tests. A system performing three standard tests
      of HRV, Anscore Health Management System, is presented. This system performs
      metronomic breathing (MT), the Valsalva Test (VT), and the Stand Test (ST). A
      normal range study with 212 healthy subjects in three centers (ages 20-80 years,
      with even age distribution, and even male and female distribution) was conducted.
      A subset of 45 subjects from the total number of subjects was selected for the
      reproducibility study, consisting of three measurements of each test. The normal
      range study showed a decrease in all the ratios with age and, for the Valsalva
      test, a difference among genders; 5th percentiles were calculated. The
      reproducibility study results, expressed as mean CV%, were 4.30% for the MT,
      6.26% for the VT, and 6.66% for the ST. HRV is the most reliable measurement of
      autonomic function; when controlled maneuvers like MT, VT, and ST are performed,
      high reproducibility is obtained, with results comparable to that observed for
      nerve conduction studies. Such reproducibility makes autonomic function testing
      more feasible as a test component in multicenter studies of different
      neurological disorders.

PMID- 11469710
TI  - Diabetic autonomic neuropathy: the clinical interpretation of improved
      technology.

PMID- 11469711
TI  - Comparison of glucose levels in dermal interstitial fluid and finger capillary
      blood.
AB  - Alternative methods for self-monitoring of blood glucose have been pursued by
      many researchers, largely in response to evidence gathered in several long-term
      studies of patients with diabetes mellitus. These studies suggest that long-term
      complications of the disease may be mitigated if the disease is intensively
      managed, a component of which is increased monitoring. Many of the alternative
      methods utilize interstitial fluid (ISF) as the diagnostic fluid, rather than
      finger blood. A time lag in the distribution of glucose from blood to the
      interstitium has been observed by many, with estimates of lag time varying from
      none to 45 min. Dermal ISF was sampled from diabetic subjects in two tests and
      compared to finger blood glucose. In the first test, data were collected over
      time in a manner that allowed a cross-correlation analysis to predict an average
      lag time. Information from this test was then used as input to a data collection
      format for a method comparison test of 691 patients with diabetes in which ISF
      data were collected immediately after the finger blood reference and 15 min after
      the reference. An average lag time of about 25 min was determined from the cross
      correlation analysis, with the correlation error reduced by three-fourths within
      a 15-min lag time. In the method comparison test, the correlation coefficient
      between finger blood glucose and ISF glucose improved from 0.923 to 0.951, and
      the percentage of data in the A zone of the Clarke Error Grid rose from 80.2% to
      90.6% for the ISF glucose data collected at no lag and 15-min lag, respectively.
      Dermal ISF glucose measurement might be a reasonable alternative to blood glucose
      measurement for patients routinely monitoring ambient glycemia, although more
      testing in the sensitive hypoglycemic range is needed to clarify what might
      happen in cases of rapidly changing glucose.

PMID- 11469712
TI  - New imaging techniques for cardiovascular autonomic neuropathy: a window on the
      heart.
AB  - Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes,
      which results in disabling clinical manifestations and may predispose to sudden
      cardiac death. Recently, direct scintigraphic assessment of cardiac sympathetic
      integrity has become possible with the introduction of radiolabeled analogues of
      norepinephrine, which are actively taken up by the sympathetic nerve terminals of
      the heart. This article reviews how these techniques have been utilized to
      improve understanding of CAN complicating diabetes. Quantitative scintigraphic
      assessment of cardiac sympathetic innervation heart is possible with either
      [123I]-metaiodobenzylguanidine (MIBG) and single photon emission computed
      tomography (SPECT) or [11C]-hydroxyephedrine (HED) and positron emission
      tomography (PET). Studies in diabetic patients have explored the sensitivity of
      these techniques to detect CAN, characterize the effects of glycemic control on
      the progression of CAN and evaluate the effects of CAN on myocardial
      electrophysiology, blood flow regulation and function. Deficits of left
      ventricular (LV) [123I]-MIBG and [11C]-HED retention have been identified in
      diabetic subjects without abnormalities on cardiovascular reflex testing
      consistent with increased sensitivity to detect CAN. Poor glycemic control
      results in the progression of LV tracer deficits, which can be prevented or
      reversed by the institution of near-euglycemia. Deficits begin distally in the LV
      and may extend proximally. Paradoxically, however, absolute HED retention is
      increased in the proximal segments of the severe CAN subjects consistent with
      regional "hyperinnervation." These regions also exhibit abnormal blood flow
      regulation. Impaired myocardial MIBG uptake correlates with altered LV diastolic
      filling and myocardial electrophysiological deficits and is predictive of sudden
      death. Scintigraphic studies have provided unique insights into the effects of
      diabetes on cardiac sympathetic integrity and the pathophysiological consequences
      of LV sympathetic dysinnervation. Future studies using complementary
      neurotransmitter analogues will allow different aspects of regional dysfunction
      to be characterized with the aim of developing therapeutic strategies to prevent
      or reverse CAN.

PMID- 11469713
TI  - Accuracy of glucose meter use in gestational diabetes.
AB  - Glucose monitoring is essential for the successful management of gestational
      diabetes. The accuracy of glucose meters is typically determined over a much
      wider range of glucose values than that commonly encountered in gestational
      diabetes. The objective of our study was to look at the accuracy of self
      monitoring glucose meters in a clinic setting over a range of glucose values seen
      in gestational diabetes. We retrospectively analyzed 107 case records of subjects
      with gestational diabetes, each of whom had three simultaneous laboratory and
      glucose meter glucose tests. The results were compared using the performance
      goals that (1) all of glucose meters should have readings within 10% of the
      reference value and (2) the error grid analysis in the standard format and a
      modified version suitable for gestational diabetes. We also examined the range of
      the differences from the reference value. Nearly half of the values (47%) were in
      excess of 10% of the reference range (either above or below). Close to 15% were
      in excess of 20% difference from the reference range. Standard error grid
      analysis showed that 96% of the values fell within sections A of the error grid
      which are considered acceptable, and 100% fell within sections A and B,
      differences which are generally considered to have no major impact on care. The
      modified version of the error grid analysis demonstrated that 39% of the values
      were outside the acceptable range. Within subjects, a substantial number (26%)
      had a range of differences that exceeded 20% difference between each other.
      Although the meters give reasonable results that might be acceptable for general
      diabetes care, the results provide some cause for concern in the management of
      gestational diabetes. Given the need for precision in the setting of pregnancy
      particularly in making the decision of whether to start or withhold insulin
      therapy, caregivers need to be cognizant of these inaccuracies.

PMID- 11469714
TI  - Impaired absorption and omission of insulin: a novel method of detection using
      the diabetes advisory system computer model.
AB  - The Diabetes Advisory System (DIAS) is a decision-support program developed to
      assist insulin dose adjustment in type 1 diabetes. In this paper, we show how it
      might be used to identify impaired absorption or omission of insulin in patients
      with poorly controlled blood glucose. An evaluation of glucose results from four
      outpatients with persistent hyperglycemia is presented (age 19-48 years with type
      1 diabetes for 13-18 years of duration, HbA1c 9.4-13.6%). Each had completed a 4
      day record of blood glucose (BG, pre-meal and bedtime), dietary (carbohydrate)
      intake, and insulin doses (with injection sites). From these data, DIAS modeled a
      glucose profile (simulated glucose, SG) for the same period. Qualitative
      assessments were made of differences between BG and SG, and selective reduction
      or complete removal of insulin doses where BG >> SG. Large improvements in
      modeling were attributed to either impaired absorption or omission of insulin.
      Confirmation of these problems was sought from the patients by detailed
      consultation and physical examination. Impaired insulin absorption was suspected
      in two patients, both having significant injection site abnormalities. Insulin
      omission was suspected in the other two subjects. Both had normal injection
      sites, and one admitted to missing doses. Following retraining, data from three
      patients showed noticeable improvements in overall modeling as well as glucose
      control. Using DIAS in the evaluation of patients with type 1 diabetes may
      highlight previously unrecognized injection site abnormalities or insulin dose
      omission. This could assist rational optimization of insulin therapy in cases of
      persistently poor glucose control.

PMID- 11469715
TI  - Epidermal growth factor receptor as a target: recent developments in the search
      for effective new anti-cancer agents.
AB  - A number of cancer chemotherapeutics targeting the epidermal growth factor
      receptor (EGFR) are in development. These compounds were designed to either bind
      to the EGFR or inhibit signal transduction after receptor activation. Classes of
      inhibitory compounds include small molecules and humanized monoclonal antibodies.
      Many of these compounds are relatively far advanced in development. Proof of
      principle, with evidence of anti-tumour activity and inhibition of EGFR
      activation/phosphorylation, has already been demonstrated in some instances.
      Although these new compounds offer exciting opportunities, they bring with them
      real challenges in terms of the selection of appropriate trial designs as well as
      surrogate endpoints.

PMID- 11469716
TI  - Update on antifolate drugs targets.
AB  - Antifolate drugs are molecules directed to interfere with the folate metabolic
      pathway at some level. They can be recognized among the first rationally designed
      compounds applying the principle of structural analogy with the substrate
      developing the antimetabolite strategy. This strategy has taken advantage of the
      basic different features of the microbial and human folate metabolism and
      therefore allows targeting the pathway at different steps generating a
      specificity tools for Medicinal Chemists. Two main problems are giving renewed
      importance to such targets and therefore improving the efforts to discover new
      targets in the folate metabolism area. The first one is the increasing resistance
      to the present drugs due to different mechanisms such as the enzyme modification
      and the increased production of enzymes with not well recognized importance. The
      second one is the development of techniques directed to highlight the
      interference at genetic level of molecular probes as antifolate drug to develop
      new enzymes previously unknown. This approach is defined as genetic approach to
      drug discovery, from gene to drugs. The present article describes the importance
      in drug design and discovery of some antifolate targets among the best known at
      the present status of research such as thymidylate synthase (TS), dhydrofolate
      reductases, (DHFR) serine hydroxymethyltransferase (SHMT), folyilpolyglutamyl
      synthetase (FPGS), gamma-glutamyl hydrolase (gamma-GH), glycinamide
      ribonucleotide transformylase (GARTfase), amino-imidazole-carboxamide
      ribonucleotide transformylase (AICARTfase) and Folate transporters. Discovery,
      known functions, structure/function studies and inhibition will be described.

PMID- 11469717
TI  - Targeting the expression of anti-apoptotic proteins by antisense
      oligonucleotides.
AB  - Antisense oligonucleotide (ASO) biotechnology has been widely used to inhibit the
      expression of proteins involved in human disease. ASOs are designed to bind
      messenger RNA transcripts via Watson-Crick base-pairing and inhibit synthesis of
      targeted proteins. These proteins include protein kinases, growth factors,
      glutamate receptors, anti-apoptotic proteins, and proteins involved in genetic
      disorders. Non-mRNA targets such as the RNA component of the telomerase enzyme
      are also being explored. Pre-clinical and clinical trials using ASO biotechnology
      have progressed with standard ASOs such as phosphorothioates, but newer ASO
      analogs are rapidly being developed with the idea of enhancing specificity and
      biological activity. A current major research thrust is the design and testing of
      antisense oligonucleotides as anti-cancer drugs. The primary focus of this review
      is an analysis of recent uses of ASO biotechnology to inhibit anti-apoptotic gene
      expression in tumor cells.

PMID- 11469718
TI  - Human leptin regulation and promise in pharmacotherapy.
AB  - In rodents leptin inhibits food intake, stimulates energy expenditure, reverses
      obesity, ameliorates insulin resistance, and accelerates sexual maturation. These
      potent and diverse effects have stimulated interest in exploring a role for
      leptin in the treatment of human metabolic disorders. However, the significance
      of leptin in human (patho)physiology is still being investigated. The present
      review summarizes current knowledge of leptin regulation, provides a critical
      assessment of initial experience with leptin therapy, and discusses potential
      targets for recombinant leptin therapy in humans. The results of numerous studies
      indicate that leptin is indeed a regulated human hormone: The physiological
      factors that influence leptin secretion include gender, adiposity, physical
      exercise, feeding, and caloric restriction. Several hormones, including insulin,
      glucocorticoids, estradiol, growth hormone, testosterone, somatostatin, and
      insulin-like growth factor-I also modulate leptin secretion. The results of
      initial trials of leptin therapy in humans have become available. Treatment with
      recombinant human leptin (0.028 mg/kg) induced a progressive weight loss (without
      evidence of tachyphylaxis) in a morbidly obese patient with congenital leptin
      deficiency. The weight loss averaged 1-2 kg/month, was associated with
      preservation of lean muscle mass, and was almost exclusively accounted for by
      depletion of body fat. Administration ofrecombinant leptin (0.01-0.3 mg/kg) also
      resultedin a dose-dependentweight loss among lean and obese humans with
      presumably normal leptin genotype. Thus leptin may have a therapeutic role in
      humans, but its physiological functions and regulation first need to be fully
      unravelled.

PMID- 11469719
TI  - Immunomodulating anticancer alkylating drugs: targets and mechanisms of activity.
AB  - CY and L-PAM potentiated specific anti-tumor response in addition to their
      killing effect. The immunomodulating effect of a low dose of either CY or L-PAM
      was expressed in mice bearing large s.c. MOPC-315 plasmacytoma tumors. Cured mice
      were resistant to a challenge dose of the syngeneic tumor and their spleens
      contained specific cytotoxic T cells. Induction of specific anti-tumor response
      by a low dose of alkylating drugs was due to expression of "latent anti-tumor"
      capability. This fitted with the conception that "suppressed concomitant
      immunity" occurring in tumor-bearing animals can be activated. The
      immunomodulating activity of alkylating drugs was related to enhancement of T
      cell functions:impairment of suppressor T-cell activity,enhancement of effector T
      cell activity and increase in production of cytokines at the tumor site. The
      target tumor killing activity of a low dose alkylating drug was dissociated from
      its immunomodulating activity by treating mice bearing a tumor resistant to an
      alkylating drug. A low dose of CY had an immunomodulating effect in human cancer
      such as reduction of ConA-induced suppressor cell activity in melanoma, some
      improvement in addition to use of melanoma vaccine, and potentiation of DTH in
      cancer patients. The immunomodulating effect of alkylating drugs suggest that
      their use might be beneficial not only for killing tumor cells but also for
      promoting specific anti-tumor immune response.

PMID- 11469720
TI  - New developments in anti-platelet therapies: potential use of CD39/vascular ATP
      diphosphohydrolase in thrombotic disorders.

PMID- 11469721
TI  - Analysis of mammalian cytochrome P450 structure and function by site-directed
      mutagenesis.
AB  - Over the past decade, site-directed mutagenesis has become an essential tool in
      the study of mammalian cytochrome P450 structure-function relationships. Residues
      affecting substrate specificity, cooperativity, membrane localization, and
      interactions with redox partners have been identified using a combination of
      amino-acid sequence alignments, homology modeling, chimeragenesis, and site
      directed mutagenesis. As homology modeling and substrate docking technology
      continue to improve, the ability to predict more precise functions for specific
      residues will also advance, making it possible to utilize site-directed
      mutagenesis to test these predictions. Future studies will employ site-directed
      mutagenesis to learn more about cytochrome P450 substrate access channels, to
      define the role of residues that do not lie within substrate recognition sites,
      to engineer additional soluble forms of microsomal cytochromes P450 for x-ray
      crystallography, and to engineer more efficient enzymes for drug activation
      and/or bioremediation.

PMID- 11469722
TI  - Induction of cytochromes P450.
AB  - Humans and rodents are exposed to many foreign compounds in their diet (e.g.,
      herbal supplements such as St. John's wart), in their environment (e.g.,
      organochlorine pesticides and polychorinated biphenyls), and as clinically
      prescribed drugs (e.g., rifampin and phenobarbital). In response to these
      exposures mammals have evolved mechanisms to induce proteins involved in
      xenobiotic detoxification. Metabolism by Phase I enzymes, particularly the heme
      containing monooxygenases cytochromes P450 is frequently the first line of
      defense against such xenobiotics.

PMID- 11469723
TI  - Induction of CYP1A1. The AhR/DRE paradigm: transcription, receptor regulation,
      and expanding biological roles.
AB  - The CYP1A1 gene encodes microsomal cytochrome P4501A1 that catalyzes the
      metabolism of many xenobiotics, including the oxygenation of polycyclic aromatic
      hydrocarbons (PAH). Induction of CYP1A1 enhances the metabolism of PAHs, and
      therefore, represents an adaptive response to chemical exposure in mammalian
      cells. Mechanistic studies reveal an AhR/DRE paradigm for the induction, which
      involves activation of the aryl hydrocarbon receptor (AhR) by an agonist,
      dimerization of AhR with the Ah recceptor nuclear translocator (Arnt), followed
      by binding of the AhR/Arnt heterodimer to the dioxin-responsive enhancer (DRE)
      and transcription of the gene. The AhR mediated transcription is tightly
      regulated through, at least, two mechanisms: (a) the cytoplasmic AhR interacts
      with hsp90 and an immunophilin chaperone AIP for proper folding and receptivity,
      and (b) the agonist-activated, nuclear AhR is degraded through the ubiquitin-26S
      proteasome mediated protein turnover, such that the transcription by AhR is
      controlled at a physiologically adequate level. In addition to CYP1A1 induction,
      AhR mediates a broad range of biological responses to CYP1A1 inducers, typified
      by the environmental contaminant dioxin, via modulating gene expression. Thus,
      mechanistic studies of CYP1A1 induction have provided insights into P450
      induction, PAH carcinogenesis, dioxin action, AhR function, and receptor-mediated
      mammalian gene expression.

PMID- 11469724
TI  - Hepatic cytochrome P450 regulation in disease states.
AB  - Hepatic cytochrome P450 (P450) enzyme activities and gene expression can be
      profoundly altered in disease states. In general the levels of affected hepatic
      P450 enzymes are depressed by diseases, causing potential and documented
      impairment of drug clearance and clinical drug toxicity. However, modulation of
      P450s is enzyme selective and this selectivity differs among different diseases.
      This review will concentrate on regulation of P450s in diabetes, obesity and
      infectious and inflammatory disease, conditions that affect millions of people
      worldwide every day.

PMID- 11469725
TI  - Heterotropic cooperativity of cytochrome P450 3A4 and potential drug-drug
      interactions.
AB  - Cytochromes P450 (CYP) 3A4 is the most abundant human hepatic CYP isoform
      catalyzing the metabolism of approximately 50% of therapeutic agents. In addition
      to inhibition or induction, CYP3A4 is subject to stimulation, termed homotropic
      (substrate stimulation) and heterotropic (stimulation by effectors)
      cooperativity. The heterotropic cooperativity of CYP3A4 may result from an
      increase in Vmax, a decrease in Km or a combination of the two and sometimes
      exhibits regio-selectivity when the enzyme is involved in two or more metabolic
      pathways for a single substrate. An effector of CYP3A4 can also be a substrate;
      its metabolism may or may not be inhibited by another substrate. These
      characteristics of heterotropic cooperativity of CYP3A4 have been interpreted in
      the context of two binding domains in the active site of the enzyme, two
      substrate binding plus a distinct allosteric binding site, multiple enzyme
      conformations or multiple binding sites accompanied by conformational changes.
      Examples of in vivo CYP cooperativity are rare; representative cases include
      flavone-dependent stimulation of zoxazolamine metabolism in rats and enhancement
      of CYP3A-mediated hepatic clearance of diclofenac by quinidine in monkeys.
      Effector-induced increases in CYP3A4 activity were observed during the 1'
      hydroxylation of midazolam and 4'- and 10-hydroxylation of warfarin in human
      hepatocyte systems. These data imply that CYP cooperativity has the potential to
      cause in vivo drug-drug interactions. Because cooperative and inhibitory
      responses from CYP3A4 are known to be substrate-dependent, projection of the
      pharmacokinetics of an investigational drug and CYP-associated risks of drug-drug
      interactions in humans can be very complex. Further investigation of CYP
      cooperativity is warranted.

PMID- 11469726
TI  - Cytochromes P450 in brain: function and significance.
AB  - The presence and activity of cytochromes P450 in brain regions and various brain
      cells have been extended and advanced over the last five years covered by this
      review. Using in situ hybridization and immunohistochemical techniques, many
      cytochrome P450 enzymes have been demonstrated to be present in brain and to have
      a regional rather than universal distribution. Many of these various cytochromes
      P450 have been shown to catalyze the metabolism of neurosteroids as well as other
      biologically significant compounds in brain. In addition, many cytochrome P450
      enzymes have been implicated in the metabolism of psychoactive drugs such as
      neuroleptics and antidepressants. The regulation of cytochrome P450 expression
      has been studied at greater detail, the regulation of aromatase being a prominent
      example during the last five years.

PMID- 11469727
TI  - Uncommon P450-catalyzed reactions.
AB  - Cytochrome P450 (P450) enzymes play major roles in the metabolism of drugs,
      carcinogens, steroids, eicosanoids, alkaloids, pesticides, and other important
      xenobiotics, as well as chemicals normally endogenous to the body. P450s are
      generally considered in a classical catalytic reduction-oxidation cycle and an
      odd-electron abstraction/rebound chemical mechanism that can be used to
      rationalize carbon hydroxylation, dealkylation of heteroatomic substrates,
      heteroatom oxygenation, and the oxidation of unsaturated compounds to epoxides
      and phenols. However, many other reactions are catalyzed by P450s but not
      generally appreciated. The classical catalytic mechanism requires some expansion
      to explain all of these reactions. Reactions discussed here include mechanism
      based heme inactivation, mechanism-based protein modification, 1,2-shifts, 1- and
      2-electron reductions, 1-electron oxidation, oxidative cleavage of carboxylic
      acid esters, desaturation, deformylation of aldehydes, ring formation, ipso
      mechanisms for aryl dehalogenation and O- and N-dearylation, cis-trans bond
      isomerization, several rearrangements of oxidized eicosanoids, aldoxime
      dehydration, and hydrolysis of phosphatidylcholine.

PMID- 11469728
TI  - Report of the Spine Society of Europe travelling fellows 2000.

PMID- 11469729
TI  - Chemonucleolysis: the state of the art.
AB  - This review presents the history of chemonucleolysis, the techniques,
      indications, contraindications, and complications. Presenting an historical
      overview and comparison of success rates with surgical discectomy may provide a
      fresh understanding of the controversy surrounding chemonucleolysis and establish
      its efficacy in relation to more invasive treatments. A review of the literature
      from 1973 through 1998 for chemonucleolysis, open discectomy, and microdiscectomy
      provided published success rates for these procedures, and a mean rate with
      standard deviation was determined. In the experience and opinion of the authors,
      chemonucleolysis remains a viable alternative for patients who have exhausted all
      conservative means of treatment. Proper patient selection leads to success rates
      comparable to open discectomy and microdiscectomy.

PMID- 11469730
TI  - The General Function Score: a useful tool for measurement of physical disability.
      Validity and reliability.
AB  - The General Function Score (GFS) is a disease-specific instrument consisting of
      nine items focusing on strict physical activities of daily living. It is intended
      as an alternative to the more complex scores of disability (such as the Oswestry
      Disability Index), serving as a complement to the quality of life instruments in
      the study of low back pain (LBP). It was developed from an original 17-item
      questionnaire, of which 11 of the items were tested for criterion validity in an
      observer-supervised performance test. Two items were excluded from further
      analysis because of too low a validity. The remaining nine-item GFS was tested
      for construct validity, reliability, feasibility and responsiveness in six
      different cohorts: 297 patients with chronic low back pain (cohort 1), an age-
      and sex-matched control group of 287 randomly allocated Swedish citizens (cohort
      2), three separate groups of patients admitted for surgery due to low back
      disorders (cohorts 3-5) and outpatients with spinal disorders (cohort 6).
      Correlations were tested with the Spearman Rank correlation coefficient,
      differences between groups with the Mann-Whitney test and the internal
      consistency with the Cronbach's coefficient alpha. The GFS total scores showed
      correlations of 0.78, 0.81 and 0.88 in the three aspects of the performance test.
      The response rate was 98.3-100%. The mean time to complete the questionnaire was
      1.2 min. The internal consistency was 0.69 and 0.86 in cohorts 1 and 2
      respectively. The test-retest correlation was 0.88. The GFS showed a high
      responsiveness to difference and change. The effect size was 0.82-0.96 in
      surgically treated disc herniation and 0.55-0.85 in spondylolisthesis. The GFS is
      a highly valid and reliable instrument with good responsiveness and feasibility,
      useful for evaluation of physical disability.

PMID- 11469731
TI  - Nonorganic pain drawings are associated with low psychological scores on the
      preoperative SF-36 questionnaire in patients with chronic low back pain.
AB  - The Short Form 36 questionnaire (SF-36) measures general health and well-being.
      Within the last 5 years it has been used increasingly to characterise patients in
      the medical literature. Relatively few studies have used the SF-36 on patients
      with chronic low back pain undergoing preoperative evaluation, but results
      suggest that it may be predictive of surgical outcome. Pain drawings are a
      routine part of evaluation prior to spinal surgery in several centres, since
      their classification of organic or nonorganic has been shown in some studies to
      correlate well with psychological characteristics predicting poor outcome. The
      purpose of the present study was to assess possible correlations between
      nonorganic pain drawings and the psychological scales in the SF-36. We included
      128 patients in the study, all of them referred from other hospitals. Previous
      spinal surgery had been undergone by 25%, and 59% required daily medication
      because of low back pain. All patients completed pain drawings using predefined
      symbols These pain drawings were scored dichotomously as organic or nonorganic
      based on a brief description of a typical nonorganic characteristics. Patients
      also completed the Danish version of the SF-36 questionnaire. Statistical
      analysis was performed using logistic regression analysis. The pain drawing
      classification was used as the dependent variable and scores on the eight scales
      of the SF-36 as independent variables. P values of <0.05 were considered
      significant. The mean scores of the patient population on all eight scales were
      significantly lower than Danish norms. The only scales that correlated with the
      presence of nonorganic pain drawings were emotional role (RE) and mental health
      (MH), both measuring psychological health. The odds ratio (OR) of receiving a
      nonorganic pain drawing was 22 (95% confidence interval, or CI, 7-65) if the
      scores on RE and MH were more than 2 standard deviations (SD) below the Danish
      norm. This is the first study providing evidence that pain drawing ratings are
      influenced by the psychological scales of the SF-36. The clinical relevance of
      this observation regarding prediction of outcome after spinal surgery should be
      assessed in future studies.

PMID- 11469732
TI  - Absence of back disorders in adults and work-related predictive factors in a 5
      year perspective.
AB  - Factors important for avoiding back disorders in different age-groups have seldom
      been compared and studied over time. We therefore set out to study age-related
      differences in socio-economic and work-related factors associated with the
      absence of back disorders in a 5-year comparative cohort study using a mailed
      questionnaire. Two subgroups (aged 25-34 and 54-59 years) derived from a
      representative sample of the Swedish population were followed at baseline, 1 year
      and 5 years. Questions were asked about the duration of back pain episodes,
      relapses, work changes and work satisfaction. A work adaptability, partnership,
      growth, affection, resolve (APGAR) score was included in the final questionnaire.
      Multivariate logistic regression was used to identify factors predicting the
      absence of back disorders. Absence of physically heavy work predicted an absence
      of back disorders [odds ratio (OR), 2.86; 95% confidence interval (CI), 1.3-6.3]
      in the older group. In the younger age-group, the absence of stressful work
      predicted absence of back disorders (OR, 2.0; 95% CI, 1.1-3.6). Thirty-seven per
      cent of the younger age-group and 43% of the older age-group did not experience
      any back pain episodes during the study period. The exploratory work APGAR scores
      indicated that back disorders were only associated with lower work satisfaction
      in the older group. The analyses point out the importance of avoiding perceived
      psychological stress in the young and avoiding perceived physically heavy work in
      the older age-group for avoiding back disorders. The results suggest a need for
      different programmes at workplaces to avoid back disorders depending on the age
      of the employees concerned.

PMID- 11469733
TI  - Is the efficacy of the Cloward procedure overestimated? Technique of evaluation
      affects the outcome.
AB  - The purpose of the present study was to investigate the influence of the
      evaluation technique on the outcome of the Cloward procedure in cervical
      radiculopathy. The retrospective study included 94 consecutive patients operated
      on with anterior decompression and fusion with heterologous bone (Surgibone,
      Unilab). There were 56 men and 38 women, with a mean age of 48 years (range 27-78
      years). Sixty-six patients had a single-level fusion, 26 a two-level fusion and
      one patient had a three-level fusion. The follow-up rate was 91/94 (97%) and
      evaluation was performed by an independent observer. Pain was quantified by
      visual analogue scale (VAS, range 0-100), functional disability by the new
      functional index Cervical Spine Functional Score (CSFS, range 0-100) and by the
      Neck Pain Disability Index (NPDI, range 0-100). The overall clinical outcome was
      assessed as excellent, good, fair or poor by both the patient and by the
      independent observer using Odom's criteria. At a mean follow-up of 26 months
      (range 12-56 months) the mean pain index was 39 (range 0-98), the mean CSFS 39
      (range 0-85) and the mean NPDI 32 (range 0-76). The classification of the
      observer was 37% excellent, 40% good, 17% fair and 6% poor, and that of the
      patient was 53% excellent, 23% good, 20% fair and 4% poor. In the group
      classified as good by the observer, all scores were above 40, suggesting
      considerable remaining symptoms, and only 50% had returned to work. The results
      suggest that previous reports on the Cloward procedure using categorizations into
      excellent, good, fair or poor have overestimated the efficacy of the procedure.
      Only an excellent, but not a good, result as classified by the patient or an
      independent observer reflects a successful outcome. Neither of the variables
      studied seems independently sufficient for a balanced reflection of the outcome.
      The results suggest pain (VAS) as the primary outcome measurement, which,
      combined with the overall evaluation by the independent observer and work status,
      gives a multidimensional expression of the outcome.

PMID- 11469734
TI  - Morphometry of the lower lumbar vertebrae in patients with and without low back
      pain.
AB  - The authors made several measurements in the lower lumbar vertebrae of patients
      with and without low back pain. Our objective was to determine the allometric
      relationships between different dimensions of the lumbar canal, the effects on
      these from degenerative disease, and differences between the symptomatic and
      asymptomatic populations. We compared 119 patients suffering from low back and
      sciatic pain and 39 subjects without lumbar symptoms as determined by computed
      tomography (CT). The following measurements were made: sagittal diameter of the
      canal, interpedicular distance, interarticular distance, and anteroposterior
      diameter of lateral recess and foramen. With respect to the patients with lumbar
      pain, the asymptomatic group proved to have wider foramina from L3 to L5 and
      wider sagittal diameters in S1. The patients with canal stenosis revealed lower
      figures for all diameters of the central canal, lateral recess of L4, and
      foramina of L4 and L5. Patients with lumbarization showed smaller diameters of
      the central canal. CONCLUSION: There is an allometric relationship between the
      dimensions of the central canals. This relationship is less evident with lateral
      canals. The patients without lumbar symptoms had wider foramina and sagittal
      diameters in S1 than those with lumbar symptoms. Of these, patients who developed
      symptoms of canal stenosis demonstrated smaller diameters in central and lateral
      canals. Of the developmental anomalies, lumbarization proved to be associated
      with canal stenosis due to smaller diameters of the central canals.

PMID- 11469735
TI  - Graf ligament stabilisation: mid- to long-term follow-up.
AB  - Previous studies have looked at early follow-up of the Graf ligament
      stabilisation system. We present mid- to long-term results of this procedure. A
      retrospective review of Graf ligaments inserted since 1993 was undertaken. A
      total of 51 patients were reviewed. Pre-operative Oswestry Disability Index
      scores were compared to post-operative scores recorded via a postal
      questionnaire. There were 28 men and 23 women. The average age was 41 years
      (range, 2267 years). The mean pre-operative score was 46 (range, 22-78), the mean
      follow-up time was 51 months (range, 23-84 months) and the mean post-operative
      score was 40 (range, 0-82). There were 12 complications (4 requiring further
      surgery), and seven patients went on to require bony fusion procedures. Forty one
      per cent of the group would choose not to have the operation again. Longer-term
      results of this technique are not as encouraging as earlier studies. The
      continued use of this procedure should be viewed with caution.

PMID- 11469736
TI  - The use of allograft (and avoidance of autograft) in anterior lumbar interbody
      fusion: a critical analysis.
AB  - The aim of this report is to analyze the validity of allograft in anterior lumbar
      interbody fusion. Forty-three patients underwent anterior lumbar interbody fusion
      using allograft in the period between 1995 and 1998. All suffered from crippling
      chronic low back pain with or without sciatica. Discogenic disease was verified
      in 40 cases by discography. All patients were investigated preoperatively with
      magnetic resonance imaging (MRI). The surgical technique is described. Follow-up
      radiographs were performed postoperatively, then at 1.5, 3, 6 and 12 months, as
      required. Radiological fusion was confirmed in all single-level fusions (100%,
      n=24). In two-level fusions the rate was 93% (n=28/30). However, radiological
      union could only be confirmed in 11 of the 12 levels in the three-level fusions.
      Allograft offers a better alternative to autograft for anterior lumbar interbody
      fusion. Donor site morbidity is avoided, hospital stay is shorter and fusion
      rates are satisfactory.

PMID- 11469737
TI  - Recovery of impaired muscle function in severe sciatica.
AB  - This is a prospective cohort study of patients with acute treated severe
      sciatica. The objectives of the study are, firstly, to describe the recovery of
      muscle performance by manual and isokinetic muscle testing in patients with acute
      severe sciatica over 1 year, and secondly, to discuss the potential clinical
      relevance of the isokinetic testing of the ankle for patients with acute
      sciatica. In clinical daily practice, muscle performance is evaluated by means of
      isometric manual tests. Different authors using manual muscle tests have reported
      the long-term outcome of the muscle function in patients with sciatica. Overall,
      the results are good in terms of the recovery of muscle strength. However, it is
      not clear whether the isometric strength is sufficiently relevant to evaluate the
      more complete muscle performance of the affected muscles in patients with
      sciatica. This study presents data on the muscle recovery measured with manual
      testing and isokinetic testing of patients with severe sciatica. Consecutive
      patients admitted to the Cantonal Hospital for conservative management of severe
      acute sciatica were eligible for inclusion in the study. Patients were evaluated
      at admission, discharge, and follow-up at 3, 6, and 12 months. All the visits
      included a standardized clinical examination and the completion of
      questionnaires. Imaging and electromyography were conducted at the first visit.
      Isokinetic muscle tests at 30 degrees/s and 120 degrees/s were performed at
      discharge and follow-up visits. Manual and isokinetic tests were performed on
      foot and ankle flexor and extensor muscles. Eighty-two consecutive patients (66%
      men), with a mean age of 43 (+/-10.3) years, entered the study. The prevalence of
      major muscle weakness was low, with 7% of patients unable to perform toe walking
      and 11% unable to walk on the heel at visit one. Moreover, motor deficit defined
      as a score of 4 or less (out of 5) was found in 15% of subjects at the first
      evaluation. Such severe deficits were not found during the last three visits. The
      isokinetic tests showed a higher prevalence of muscle function impairment. At
      visit 5, the isokinetic test showed impaired muscle function recovery from 23% to
      32%, while the manual test showed almost full recovery. The issues of agreement
      between manual and isokinetic muscle testing are discussed. In this selected and
      homogeneous cohort of patients, the prevalence of motor deficit was rather low
      and the outcome excellent according to the results of the manual testing.
      Isokinetic muscle tests showed a higher prevalence of deficit and a much slower
      recovery. The manual muscle test is a crude clinical test. For more indepth
      muscle performance evaluation, additional testing may be necessary, especially
      for those patients with physically demanding jobs or activities.

PMID- 11469738
TI  - CT scans versus conventional tomography in acute fractures of the odontoid
      process.
AB  - Four different radiological diagnostic methods were compared as to their
      diagnostic relevance in the analysis of odontoid fractures. Thirty-one patients
      with fresh odontoid fractures were investigated using standard anteroposterior
      and lateral radiographs, conventional tomography, axial computerized tomography
      and two-dimensional reconstruction in the sagittal and the coronal planes. As a
      control, 13 patients without odontoid fractures were examined. The results of the
      different investigations were correlated with the actual (clinical and/or intra
      operative) findings. The coefficients of correlation for the conventional
      tomography and two-dimensional reconstruction were kappa=0.774 and kappa=0.907,
      respectively. For conventional radiography and axial computerized tomography
      (CT), the coefficients were clearly lower, at kappa=0.364 and kappa=0.627,
      respectively. The less time-consuming CT examination with sagittal and coronal
      reconstructions is equivalent with respect to diagnostic accuracy and can,
      therefore, replace conventional tomography in the evaluation fractures.

PMID- 11469739
TI  - Finite element model of the Jefferson fracture: comparison with a cadaver model.
AB  - This study tries to explain the reason why the Jefferson fracture is a burst
      fracture, using two different biomechanical models: a finite element model (FEM)
      and a cadaver model used to determine strain distribution in C1 during axial
      static compressive loading. For the FEM model, a three-dimensional model of C1
      was obtained from a 29-year-old healthy human, using axial CT scans with
      intervals of 1.0 mm. The mesh model was composed of 8200 four-noded isoparametric
      tetrahedrons and 37,400 solid elements. The material properties of the cortical
      bone of the vertebra were assessed according to the previous literature and were
      assumed to be linear isotropic and homogeneous for all elements. Axial static
      compressive loads were applied at between 200 and 1200 N. The strain and stress
      (maximum shear and von Mises) analyses were determined on the clinically relevant
      fracture lines of anterior and posterior arches. The results of the FEM were
      compared with a cadaver model. The latter comprised the C1 bone of a cadaver
      placed in a methylmethacrylate foam. Axial static compressive loads between 200
      and 1200 N were applied by an electrohydraulic testing machine. Strain values
      were measured using strain gauges, which were cemented to the bone where the
      clinically relevant fracture lines of the anterior and posterior arches were
      located. As a result, compressive strain was observed on the outer surface of the
      anterior arch and inferior surface of the posterior arch. In addition, there was
      tensile strain on the inner surface of the anterior arch and superior surface of
      the posterior arch. The strain values obtained from the two experimental models
      showed similar trends. The FEM analysis revealed that maximum strain changes
      occurred where the maximum shear and von Mises stresses were concentrated. The
      changes in the C1 strain and stress values during static axial loading
      biomechanically prove that the Jefferson fracture is a burst fracture.

PMID- 11469740
TI  - A technique for frameless stereotaxy and placement of transarticular screws for
      atlanto-axial instability in rheumatoid arthritis.
AB  - The aim of the present study was to outline a new surgical technique and describe
      how, in a clinical setting, computer-generated image-guidance can assist in the
      planning and accurate placement of transarticular C1/C2 screws inserted using a
      minimally invasive exposure. Forty-six patients with atlanto-axial instability
      due to rheumatoid arthritis underwent posterior stabilisation with transarticular
      screws. This was achieved with a minimal posterior exposure limited to C1 and C2
      and percutaneous screw insertions via minor stab incisions. The Stealth Station
      (Medtronic Sofamor Danek, Memphis, Tenn., USA) was used for image guidance to
      navigate safely through C2. Reconstructed computed tomographic (CT) scans of the
      atlanto-axial complex were used for image guidance. It was possible to perform
      preoperative planning of the screw trajectory taking into account the position of
      the intraosseous portion of the vertebral arteries, the size of the pars
      interarticularis and the quality of bone in C2. Screws could be inserted
      percutaneously over K-wires using a drill guide linked to the image-guidance
      system. Preoperative planning was performed in all 46 patients and accurate
      registration allowed proposed screw trajectories to be identified. Thirty-eight
      patients had bilateral screws inserted and eight had a unilateral screw. A total
      of 84 screws were inserted using the Stealth Station. There were no neurovascular
      injuries. This technique for placing transarticular screws is accurate and safe.
      It allows a minimally invasive approach to be followed. Image guidance is a
      useful adjunct for the surgeon undertaking complex spinal procedures.

PMID- 11469741
TI  - The rehabilitation of brain injured children: the case for including physical
      exercise and virtual reality.
AB  - Whilst substantial advances in rehabilitation programmes for brain injured
      children have been made, there is still a fundamental need to improve
      understanding of the rehabilitation process and how this can be incorporated into
      practice. It is argued here that taking a neurological approach to improving
      cognition, mood and social functioning is likely to be of great benefit to the
      patient. Theoretical reasons are outlined as to why activities such as
      interactive exercise can improve both the structure and function of the brain,
      and it is recommended that further research is carried out to establish the
      effectiveness of these types of activities.

PMID- 11469742
TI  - Resting energy expenditure of children attending a rehabilitation programme
      following head injury.
AB  - STATEMENT OF PURPOSE: Increased resting energy expenditure following head injury
      is well documented, but whether this increase extends into rehabilitation and
      whether this is affected by changes in body composition have not been studied.
      The aim of this study was to determine whether children attending a
      rehabilitation program following head injury had altered energy expenditure and
      body composition. METHODS: Measurements of resting energy expenditure by indirect
      calorimetry were performed in 21 head injured children (mean age 10.2 +/- 3.8
      years). Measurement of body composition was performed using total body potassium.
      RESULTS: Measured resting energy expenditure values were widely distributed,
      ranging from 52.3-156.4% of predicted values, yet the mean percentage predicted
      using Schofield weight, Schofield weight and height and World Health Organization
      predictive equations were 97.5%, 97.4% and 98.6%, respectively. Mean percentage
      of expected total body potassium for weight, height and age for head injured
      children were 85.1 +/- 15.5%, 89.1 +/- 14.1% and 86.9 +/- 15.9%, thus all showed
      significant depletion. CONCLUSIONS: During rehabilitation, using predictive
      equations to estimate resting energy expenditure in this group revealed a small
      bias on average but very large bias at the individual level. Head injured
      children had altered resting energy expenditure and body composition.

PMID- 11469743
TI  - Neuroimaging in hyperkinetic children and adults: an overview.
AB  - The application of brain imaging techniques to children with Attention
      Deficit/Hyperactivity Disorders is reviewed, stressing methodological aspects.
      Findings are still provisional, but suggest minor structural changes in frontal
      and candate areas, especially on the right side. Functional studies suggest
      reduced activation in these and other areas. The techniques do not yet contribute
      to individual diagnosis.

PMID- 11469744
TI  - Assessment of speed of processing after paediatric head trauma: need for better
      norms.
AB  - The neuropsychological test scores of 47 children with traumatic head injury
      (THI), aged 9-14 years, were evaluated to determine the relative contributions of
      severity of injury (length of coma) and age on performance. Stepwise regression
      analyses revealed that age consistently explained a statistically significant
      proportion of the variance on the Trail Making Test (TMT) and Finger Tapping Test
      (FTT), even after accounting for injury severity. However, logistic regression
      analyses indicated that currently available age-based norms for these tests did
      not improve classification of mild-moderate vs. severe injuries, as compared to a
      system based exclusively on raw scores. It is concluded that, whereas age is an
      important consideration when assessing children with THI, available age-based
      norms for some common paediatric neuropsychological tests do not appear to be
      sufficiently stratified or robust to fully capture these age effects. It is
      suggested that more comprehensive age-referenced norms, based on larger and more
      adequately stratified samples, are needed. In addition, some practical
      implications of these findings are discussed.

PMID- 11469745
TI  - Referrals, diagnoses, and neuropsychological findings in an outpatient sample of
      German children and adolescents with brain dysfunction.
AB  - Although the necessity of outpatient neuropsychological rehabilitation of
      neurologically impaired children and adolescents is widely accepted, outpatient
      services, however, are scarcely supplied. Furthermore, there are only a few
      analyses of the requirement of such services for children and adolescents. This
      investigation presents the results of an empirical analysis of referral sources,
      referral diagnoses, demographic characteristics, and neuropsychological findings
      for an outpatient neuropsychological utilization sample of children and
      adolescents with brain dysfunction. Finally, suggestions for the further
      development of adequate rehabilitation programmes are discussed.

PMID- 11469746
TI  - Rehabilitation of cerebral palsy in a developing country: the need for
      comprehensive assessment.
AB  - Records of 100 children with cerebral palsy from rural India attending a cerebral
      palsy clinic were analysed to determine the frequency of associated handicaps and
      to evaluate whether appropriate intervention had been instituted for these
      handicaps. All the children underwent speech, hearing, psychological,
      ophthalmologic, neurological, physical, functional and orthopaedic evaluations on
      their visit to the clinic. History was elicited from the parents of the patients
      to identify which of the disabilities were recognized either by them or their
      primary care physician, and whether any intervention had been instituted. The
      mean age of the patients was 6.9 years. Eighty-two per cent of the children had
      one or more disabilities apart from locomotor disabilities, visual defects being
      the commonest (54%). Fifty-four per cent of the children had more than one
      associated disability. Although 43% of the patients had been referred by a
      primary care physician, one or more associated disabilities had not been
      recognized and epilepsy was the only associated problem that had been treated
      prior to the evaluation. The study emphasizes the need for comprehensive
      evaluation of all children with cerebral palsy to enable proper rehabilitation.

PMID- 11469747
TI  - Recurrent and migratory reflex sympathetic dystrophy in children.
AB  - Reflex sympathetic dystrophy is a syndrome characterized by superficial pain and
      tenderness associated with swelling, vasomotor instability, and dystrophic
      changes of the skin. In children, it is rarely reported and is felt to have a
      more benign and self-limited course. This case illustrates that, in children,
      reflex sympathetic dystrophy can occur without any previous history of trauma,
      and may be recurrent and migratory. A review of the literature is included. An 11
      year-old girl, with no history of trauma, presented in 1992 with spontaneous
      onset of right leg pain. She was diagnosed with reflex sympathetic dystrophy, and
      she was treated unsuccessfully with oral medications. Her symptoms then resolved
      in 2 weeks after receiving epidural anaesthesia and aggressive physical therapy.
      Over the next 5 years, she presented to the paediatric rehabilitation clinic
      three times with recurrent RSD in her bilateral arms. The first two times were
      refractory to conservative management and resolved with four stellate ganglion
      blocks. The third recurrence persisted with three stellate ganglion blocks and
      resolved with gabapentin.

PMID- 11469748
TI  - Children, disability and rehabilitation in history.
AB  - Pediatric Rehabilitation is starting a new section in the journal. 'Voices from
      the Past' will combine two forms of articles. The first will be reviews of, and
      where possible, republication of the 'classic' articles in the field of
      paediatric rehabilitation. Summaries and discussions of these seminal
      contributions will at least be presented. The second will be scholarly studies of
      historical topics within the fields of paediatric rehabilitation, childhood and
      disability. Recent research in the histories of childhood and disability is
      reviewed in this essay.

PMID- 11469749
TI  - Drug discovery.

PMID- 11469750
TI  - QSAR of antineoplastics IV: Hansch analysis of N-(7-indolyl)benzenesulfonamides
      against KB human nasopharynx carcinoma, colon 38 murine adenocarcinoma and P388
      murine leukemia cell lines.
AB  - Hansch analysis of recently reported antitumor activities of novel N-(7
      indolyl)benzenesulfonamide derivatives against KB human nasopharynx carcinoma,
      colon 38 murine adenocarcinoma and P388 murine leukemia cell lines reveals that
      the pattern of receptor interactions in human KB cells differs from that in
      murine (colon 38 and P388 leukemia) cells. The latter two activities are
      autocorrelated and show similar receptor specificity. It seems that two binding
      sites, one interacting with the indole fragment and another with phenyl fragment
      of the indolylbenzenesulfonamide compounds, are present on the murine cell
      receptors (colon 38 and P388 leukemia) while only the latter binding site is
      active on the human KB cell receptors. For the activity against KB cells, a para
      methyl or paramethoxy substituent on the phenyl ring of benzenesulfonamide moiety
      greatly enhances the activity. For the other two activities, a 3-chloro or 3
      cyano substituent on indole nucleus enhances activities, while presence of
      bulkier meta or para substituent on the phenyl ring decreases activities.
      Presence of an ortho substituent on the phenyl ring appears to be detrimental for
      all the three activities. Equations generated by both QSAR and QAAR studies are
      quite robust as evidenced from cross-validation by 'leave-one-out' technique.

PMID- 11469751
TI  - QSAR of antineoplastics V: Exploration of receptor interaction sites of antitumor
      N-(7-indolyl)benzenesulfonamides targeting GI phase using electrotopological
      state atom index.
AB  - Quantitative structure activity relationship (QSAR) study of antiproliferative
      activities of N-(7-indolyl)benzenesulfonamides with electrotopological state atom
      (ETSA) index corroborates the conclusions of the previously reported Hansch
      analysis that the structural requirements for interactions with receptors of
      human KB nasopharynx cell line are different from that for murine colon 38 and
      P388 leukemia cell lines. The study suggests that both phenyl ring and indole
      moiety are the important receptor interaction sites present on the ligands for
      the murine cell lines, while the latter site does not appear to play significant
      role in case of human KB cell carcinoma.

PMID- 11469752
TI  - Synthesis and evaluation of asperlicin analogues as non-peptidal cholecystokinin
      antagonists.
AB  - The SAR of Asperlicin analogues is reported, leading to bioactive 1,4
      benzodiazepine-2-ones, which were prepared in a 3 step reaction sequence. The
      Asperlicin substructure was built up using Tryptophan and readily available 2
      amino-acetophenones. This template, containing a 1,4-benzodiazepin-2-one moiety
      with a 3-indolmethyl side chain, was transformed into mono- and di-substituted 3
      indol-3'-yl-methyl-1,4-benzodi-azepine-2-ones by selective alkylation and
      acylation reactions. The SAR optimization of the 1,4-benzodiazepine scaffold has
      included variations at the 5-, 7-, 8-position, at the N1, N-indole nitrogen and
      the configuration of the C3-position. The most active Asperlicin analogue, having
      an IC50 of 1.6 microM on the CCKA receptor subtype, was obtained from Tryptophan
      in only 3 steps in an overall yield of 48%.

PMID- 11469753
TI  - A method for assessing the side chain orientations of histidine, asparagine, and
      glutamine as well as the protonation forms of histidine in protein structures.
AB  - In protein X-ray crystallography, it is sometimes impossible to distinguish N and
      O in amide side chains and N and C in His side chains, resulting in the 'flipped'
      conformations in these side chains. We have developed a simple, but effective,
      approach to assess the side chain orientations of His. Asn, and Gln as well as
      the protonation forms of His in protein structures. This method finds the most
      favorable side chain orientation and His form by calculating the van der Waals
      interaction and hydrogen bonding energies around each residue in question. This
      evaluation is repeated until consistent results are obtained. Our approach was
      applied to four proteins and in overall approximately 25% of His, Asn, and Gln
      were evaluated as 'flipped' and 63% of the imidazole rings were suggested to have
      a polar hydrogen atom only on N epsilon2. In the individual cases, it was found
      that our results were comparable to or even better than those obtained by a
      traditional method. The present approach is therefore quite useful to construct
      initial protein structures for the molecular modeling studies.

PMID- 11469754
TI  - Discovery of the first non-peptide antagonist of the motilin receptor.
AB  - A first-in-class non-peptide antagonist of the motilin receptor was identified
      through electronic screening of our corporate database against a 3D
      pharmacophore. The pharmacophore was developed from the motilin 22 residue
      endogenous peptide using NMR structural data, principles of peptide folding, and
      peptide structure activity relationships. The NMR data supported helical content
      within the peptide, and both the hydrophobic staple and N-capping box motifs were
      identified in the motilin sequence. The conformational features of these motifs
      were imposed on the peptide structure, providing a constrained conformer as a
      starting point for database searching. A trisubstituted cyclopentene lead was
      identified directly from the electronic search. Compounds in this series inhibit
      the binding of 125I-motilin to human antral smooth muscle membrane and antagonize
      motilin-induced intracellular calcium mobilization in cells expressing the human
      motilin receptor. A potent compound developed through optimization, RWJ 68023, is
      active in binding and cell-based functional assays and is also effective in
      inhibiting motilin-induced contractility in segments of rabbit duodenum. This
      orally active compound is currently undergoing clinical evaluation for the
      treatment of gastrointestinal disorders associated with altered motility.

PMID- 11469755
TI  - Conformational analysis of cyclophostin and designed analogs in comparison with
      the potent IP3 receptor agonist adenophostin A.
AB  - A conformational analysis of 5'-6"-tethered cyclophostin was carried out in
      comparison with the mother compound, adenophostin A, which has a potent IP3
      receptor agonistic activity. The global minimum 3'-endo/anti conformation of
      cyclophostin elucidated by a molecular dynamics simulation was in accord with NMR
      spectroscopic data. In contrast, the 2'-endo/syn conformation was dominant with
      respect to adenophostin A. Despite the constraint introduced by the tether, the
      spatial arrangement of the three phosphate groups and the adenine moiety, which
      are essential for the extremely high potency, was changed only moderately in
      comparison with adenophostin A. The observed high potency of cyclophostin (EC50 =
      38 nM) also indicates that it closely resembles the bioactive conformation of
      adenophostin A (EC50 = 7 nM). These results led us to estimate the probable
      active conformation of adenophostin A by comparison with the stable conformations
      of cyclophostin. Finally, two other tethered analogs were designed and are
      expected to exhibit high potencies comparable to adenophostin A.

PMID- 11469756
TI  - Rational procedure for 3D-QSAR analysis using TRNOE experiments and computational
      methods: application to thermolysin inhibitors.
AB  - The success or failure of 3D QSAR, particularly CoMFA, is most strongly
      dependent, especially for flexible compounds, on the conformation of the molecule
      used in the analysis, and on the orientation of the molecule relative to the
      other molecules in 3D space (i.e., alignment). The present study suggests a
      rational procedure for the estimation of binding conformation that uses the
      transferred nuclear Overhauser effect (TRNOE) experiment in combination with
      conformational analysis using CAMDAS (Conformational Analyzer with Molecular
      Dynamics And Sampling) program that is developed in our laboratory. In the next
      step the TRNOE-obtained conformation can be used as a reference template in order
      to obtain alignment of other ligands, that have a common binding site. In this
      step we used the SUPERPOSE program created in our laboratory, in order to
      estimate the binding conformation of other compounds, and to simultaneously
      obtain the alignment of compounds for CoMFA. The resulting CoMFA models could be
      expected to closely reproduce the interaction mode with protein represented by
      the reported X-ray results. In order to confirm the validity of our procedure
      described above, we show its application in obtaining CoMFA models of thermolysin
      inhibitors. We obtained twenty CoMFA models, and that with the highest q2 value
      (q2 = 0.701) was found to provide an interaction mode very similar to that
      represented by the X-ray results.

PMID- 11469757
TI  - In vitro antifungal activities of voriconazole and reference agents as determined
      by NCCLS methods: review of the literature.
AB  - Voriconazole (VfendTM) is a new triazole that currently is undergoing phase III
      clinical trials. This review summarizes the published data obtained by NCCLS
      methods on the in vitro antifungal activity of voriconazole in comparison to
      itraconazole, amphotericin B, fluconazole, ketoconazole and flucytosine.
      Voriconazole had fungistatic activity against most yeasts and yeastlike species
      (minimum inhibitory concentrations [MICs] < 2 microg/ml) that was similar or
      superior to those of fluconazole, amphotericin B, and itraconazole. Against
      Candida glabrata and C. krusei, voriconazole MIC ranges were 0.03 to 8 and 0.01
      to > 4 microg/ml, respectively. For four of the six Aspergillus spp. evaluated,
      voriconazole MICs (< 0.03 to 2 microg/ml) were lower than amphotericin B (0.25 to
      4 microg/ml) and similar to itraconazole MICs. Voriconazole fungistatic activity
      against Fusarium spp. has been variable. Against E oxysporum and F. solani, most
      studies showed MICs ranging from 0.25 to 8 microg/ml. Voriconazole had excellent
      fungistatic activity against five of the six species of dimorphic fungi evaluated
      (MIC90s < 1.0 microg/ml). The exception was Sporothrix schenckii (MIC90s and
      geometric mean MICs > or = 8 microg/ml). Only amphotericin B had good fungistatic
      activity against the Zygomycetes species (voriconazole MICs ranged from 2 to > 32
      microg/ml). Voriconazole showed excellent in vitro activity (MICs < 0.03 to 1.0
      microg/ml) against most of the 50 species of dematiaceous fungi tested, but the
      activity of all the agents was poor against most isolates of Scedosporium
      prolificans and Phaeoacremonium parasiticum (Phialophora parasitica).
      Voriconazole had fungicidal activity against most Aspergillus spp., B.
      dermatitidis, and some dematiaceous fungi. In vitro/in vivo correlations should
      aid in the interpretation of these results.

PMID- 11469758
TI  - Polymorphic exocellular protease expression in clinical isolates of Trichophyton
      tonsurans.
AB  - Tinea capitis continues to be an overwhelmingly prevalent disease in children.
      Despite the fact that it was recognized over a century ago, the factors that
      dictate the divergent clinical presentations seen with tinea capitis (e.g.,
      carrier state, chronic non-inflammatory infection, acute severely-inflammatory
      infection) remain unknown. Given the pathogenic role of exocellular proteases in
      dermatophyte infections and their potential immunogenic role, this investigation
      was designed to characterize strain-specific variability in fungal protease
      expression and activity in Trichophyton tonsurans isolates identified from
      children with tinea capitis.

PMID- 11469759
TI  - Partial purification and some biochemical characteristics of exocellular
      keratinase from Trichophyton mentagrophytes var. erinacei.
AB  - The dermatophyte Trichophyton mentagrophytes var. erinacei isolated from patients
      infected with tinea cruris was cultured in Sabouraud dextrose broth, from which
      an exocellular keratinase extract was obtained. The keratinase was partially
      purified with sephadix G-100 gel filtration. Some biochemical characteristics of
      the purified enzyme were examined. Its molecular weight was estimated to be
      38,000 dalton on sodium dodecyle sulfate polyacrylmide gel electrophoresis (SDS
      PAGE). The optimal pH was 5.5 and optimal temperature for the highest keratinase
      activity was 50 degrees C. The enzyme activity was specifically increased against
      guinea pig hair and fibrous protein and inhibited by
      phenylmethylsulfonylfluoride.

PMID- 11469760
TI  - Hair and scalp mycobiota in school children in Nablus area.
AB  - Hair and scalp mycobiota of 1389 clinically normal children aged 6-12 years
      attending 12 schools in the Nablus District, Palestinian Authority, was assessed
      on three occasions over 8-month period (October 1998-May 1999) using the hair
      brush technique. One hundred and one fungal species belonging to 33 genera were
      recovered: 6 dermatophytes, 16 dermatophyte-like keratinophilic fungi, and 79
      other keratinophilic fungal species. Species varied considerably in their
      frequency of occurrence and abundance based on their relative importance values
      (RIVs). The most frequent and abundant species were: Cladosporium
      cladosporioides, Cl. herbarum, Penicillium chrysogenum and Aspergillus flavus,
      Microsporum canis, Aphanoascus fulvescence and Chrysosporum sulfureum were the
      most frequent and abundant species of all dermatophytes and dermatophyte-like
      keratinophilic fungi recovered. The most frequent and abundant dermatophytes in
      different communities were M. canis in rural (RIV 0.87) and urban children
      (0.45), and Trichophyton violaceum (1.41) in refugee camp children. Chrysosporium
      species were the most frequent and abundant dermatophyte-like keratinophilic
      fungus in children from all localities followed by Aphanoascus fulvescence.
      Comparable results on the frequency and abundance of human hair and scalp
      mycobiota component fungi were obtained based on age group and sex of children.
      Higher number of species was recovered in spring months (73 species) than in
      autumn (57) and winter (44) months. Similar occurrence pattern was also noted for
      dermatophyte-like keratinophilic species and dermatophytes. Higher percentages of
      children with moderate (11-50) and heavy (< or = 50) spore loads (7.54 and 0.73,
      respectively) were found in urban school children community than in rural and
      refugee camp school children (4.7 and 0.1, respectively). Also significantly
      higher light (1-10) spore load percentages were found in rural (63.67) and
      refugee camp (62.9) than in urban children (52.6). Of all localities, school
      children with light spore load comprised the highest percentage of the children
      examined (37.4), followed by moderate (6.13), and heavy (0.41) spore load
      categories. However, children with undetected spore load comprised 36.05% of all
      children. Spore load distribution did not show clear seasonal variations in the
      study period. Higher percentages of moderate and heavy spore loads were found in
      male children (8.72 and 0.69, respectively) than in female children (3.4 and 0.1,
      respectively). However, higher percentages of undetected (38.3) or light spore
      loads (58.4) were found in females than in males (34.04 and 56.53, respectively).

PMID- 11469761
TI  - Screening of cassava and yam cultivars for resistance to anthracnose using toxic
      metabolites of colletotrichum species.
AB  - Collectotrichum gloeosporioides f. sp. manihotis and C. gloeosporioides, causal
      agents of cassava (Manihot spp.) and yam (Dioscorea spp.) anthracnose diseases,
      respectively, produce toxic metabolites in culture that fluoresce at 254 nm and
      366 nm, producing bands with Rf of 0.65 and 7.0, respectively. Symptoms induced
      on yam and cassava by the extracted metabolites were similar to those induced by
      the pathogens. Twenty-four clones of tropical D. rotundata (TDr), D. alata (TDa),
      D. esculenta (TDe), and D. cavenensis (TDc) were screened by applying toxic
      metabolites of C. gloeosporioides to their leaves and stems. Only TDr131, TDe179
      and TDc750 were resistant. Other clones were susceptible to varying degrees.
      Nineteen of the 45 clones of M. esculenta were resistant to varying degrees of
      toxic metabolites of C. gloeosporioides f. sp. manihotis. Results from in vitro
      screening of' cassava and yam clones using toxic metabolites compared favourably
      with field screening based on natural epidemics. Using toxic metabolites appears
      to be a more effective technique for screening for disease resistance than
      conventional inoculation with plant pathogens.

PMID- 11469762
TI  - Fungal populations on sunflower (Helianthus annuus) anthosphere and their
      relation to susceptibility or tolerance to Sclerotinia sclerotiorum attack.
AB  - Analysis of the fungal flora from different floret parts of various sunflower
      (Helianthus annuus) varieties showed that there are differences in both fungal
      species and frequency, depending on whether the sunflower variety is susceptible
      (SV) or tolerant (TV) to attack of the flower heads by the ascomycete pathogen
      Sclerotinia sclerotiorum. The sunflower varieties analyzed were SV: HA 300 and Z
      20028, and TV: HA 302, Z AV 8410 and Z 30629. The isolates showed different "in
      vitro" behavior as biocontrol agents. The most common types of interaction with
      Sclerotinia sclerotiorum were D2 and D2+ (hyphal contact) for isolates from SV
      and TV, while some of the isolates from TV displayed antibiosis. The
      microorganisms that colonize TV florets play a part in an indirect mechanism that
      protects flowers from ascospore germination and pathogen growth.

PMID- 11469763
TI  - Endothelin-1 and control of blood flow distribution in the lung.

PMID- 11469764
TI  - The biomechanics of what really causes navicular disease.

PMID- 11469765
TI  - Equine pulmonary and systemic haemodynamic responses to endothelin-1 and a
      selective ET(A) receptor antagonist.
AB  - Based on previous in vitro studies, we hypothesised that endothelin (ET) would
      induce vasoconstriction in the pulmonary circululation of the horse and that this
      action would be mediated via ET(A) receptors. Pulmonary and systemic haemodynamic
      responses to endothelin-1 (ET-1), a potent vasoactive endogenous peptide, were
      investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of
      exogenous ET-1 (0.1, 0.2 and 0.4 microg/kg bwt) caused significant increases in
      pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79%
      and 51% for mean PAP and CAP, respectively. The effect of ET-1 on PAP and CAP was
      rapid and transient for PAP (-10 min) but prolonged for CAP (up to 60 min). ET-1
      significantly decreased cardiac output by up to 35% and significantly increased
      systemic vascular resistance (SVR) by up to 104%. Pulmonary vascular resistance
      (PVR) showed a trend (P>0.05) to increase with 0.2 and 0.4 microg/kg bwt ET-1.
      Infusion of a selective ET(A) receptor antagonist (TBC11251) completely inhibited
      the responses to a subsequent bolus of 0.2 microg/kg bwt ET-1. We conclude that
      exogenous ET-1 exerts a potent vasoconstrictive action on the pulmonary and
      systemic circulations of the horse. These effects appear to be mediated largely
      through ET(A) receptors in both circulations. Endothelin may play a role in
      hypertensive conditions in the horse.

PMID- 11469766
TI  - Endothelin in the equine hypoxic pulmonary vasoconstrictive response to acute
      hypoxia.
AB  - Elevated concentrations of endothelin (ET), a potent endothelium-derived
      vasoactive peptide, have been reported in a number of pathophysiological
      conditions associated with pulmonary hypertension, both in the horse and other
      species. We have previously shown, both in vitro and in vivo, that the pulmonary
      and systemic vascular response to exogenous ET is mediated predominantly via
      ET(A) receptors. Our hypothesis in the present study was that ET is involved in
      the equine hypoxic pulmonary vasoconstrictive response to acute hypoxia. In this
      study, we investigated the effects of a selective ET(A) receptor antagonist on
      hypoxic pulmonary hypertension in the mature horse. Horses were exposed to a 10
      min period of hypoxia (F(I)O2 approximately 0.11) on 2 occasions, with and
      without pretreatment with the selective ET(A) receptor antagonist TBC11251 (10
      mg/kg bwt i.v.). Hypoxia increased mean pulmonary artery pressure (PAP) from
      18.3+/-0.9 (mean +/- s.e. normoxia) to 28.0+/-0.8 mmHg (hypoxia) in the session
      without ET(A) receptor antagonism. Carotid arterial pressure (CAP) also increased
      progressively throughout the period of hypoxic challenge and at the end was 153+/
      5 mmHg (hypoxia) compared to during normoxia (140+/-5 mmHg). There was no
      significant overall effect of ET(A) receptor antagonism on the haemodynamic or
      ventilatory responses to acute hypoxia. However, between 5 and 10 min of hypoxia
      there was a trend for the mean PAP to diverge in the 2 treatments, which just
      failed to reach significance at 10 min of hypoxia (P = 0.053). In conclusion,
      this study describes the haemodynamic and ventilatory changes in response to a
      period of acute hypoxia in the adult horse. The results do not support a role for
      ET as a mediator of acute HPV in the horse, but suggest that it may be involved
      as a modulator or in the slower (>10 min) phase of HPV.

PMID- 11469767
TI  - Intravenous pentoxifylline does not enhance the pulmonary haemodynamic efficacy
      of frusemide in strenuously exercising thoroughbred horses.
AB  - The present study was carried out to examine whether pentoxifylline
      administration to horses premedicated with frusemide would attenuate the exercise
      induced pulmonary arterial, capillary and venous hypertension to a greater extent
      than frusemide alone, thereby affecting the occurrence of exercise-induced
      pulmonary haemorrhage (EIPH). Using established techniques, we determined right
      heart and pulmonary vascular pressures in 6 healthy, sound Thoroughbred horses at
      rest and during exercise performed at maximal heart rate at a workload of 14 m/s
      on 3.5% uphill grade in the control (no medications), frusemide (250 mg i.v., 4 h
      pre-exercise)-control, and the frusemide (250 mg i.v., 4 h pre-exercise) +
      pentoxifylline (8.5 mg/kg bwt i.v., 15 min preexercise) treatments. Sequence of
      the 3 treatments was randomised for every horse and 7 days were allowed between
      them. In the control study, galloping at 14 m/s on 3.5% uphill grade elicited
      significant right atrial as well as pulmonary arterial, capillary and venous
      hypertension and all horses experienced EIPH as detected by the presence of fresh
      blood in the trachea on endoscopic examination. Frusemide administration was not
      attended by changes in heart rate at rest or during exercise. Although in the
      frusemide-control experiments, a significant reduction in mean pulmonary
      arterial, capillary and wedge pressures was observed both at rest and during
      galloping at 14 m/s on 3.5% uphill grade, all horses still experienced EIPH.
      Pentoxifylline administration to standing horses premedicated with frusemide
      caused nervousness, muscular fasciculations, sweating and tachycardia. Although
      these symptoms had largely abated within 15 min, there were no significant
      changes in the right atrial or pulmonary vascular pressures. Exercise in the
      frusemide + pentoxifylline experiments also caused significant right atrial as
      well as pulmonary arterial, capillary and venous hypertension, but these data
      were not found to be significantly different from the frusemide-control
      experiments. All horses in the frusemide + pentoxifylline experiments also
      experienced EIPH. In conclusion, our data indicate that pentoxifylline (8.5 mg/kg
      bwt i.v., 15 min pre-exercise) is ineffective in modifying the pulmonary
      haemodynamic effects of frusemide in exercising horses. It should be noted,
      however, that we did not examine whether erythrocyte plasticity was altered by
      the administration of pentoxifylline. Since the intravascular force exerted onto
      the blood-gas barrier of exercising horses premedicated with frusemide remained
      unaffected by pentoxifylline administration, it is concluded that concomitant
      pentoxifylline administration is unlikely to offer additional benefit to horses
      experiencing EIPH.

PMID- 11469768
TI  - Proximal interphalangeal arthrodesis in 22 horses.
AB  - The purpose of this study was to evaluate a new method of internal fixation
      technique for pastern arthrodesis. Pastern arthrodeses are performed commonly in
      horses with chronic osteoarthritis of the pastern joint or, in cases of acute
      traumatic injury to the pastern, in which the weightbearing bony column must be
      restored. Chronic osteoarthritis of the pastern is a frequent cause of lameness
      in the equine athlete and is evidenced by chronic lameness localised to the
      pastern joint, and supported radiographically by periosteal proliferation and
      loss of joint space. Nonsurgical and surgical treatments have both been described
      in the literature. Complications following pastern arthrodesis have been reported
      on several occasions and appear to focus on excessive periarticular exostoses and
      increased time in a cast due to prolonged time to bony fusion. The hospital
      records of horses presenting for pastern arthrodesis to the Rood and Riddle
      Equine Hospital in Lexington, Kentucky, were reviewed and 22 met criteria for
      inclusion in the study. Horses with chronic osteoarthritis of the proximal
      interphalangeal joint or horses with an acute traumatic injury to the pastern
      undergoing pastern arthrodesis with one of the following techniques were included
      in the study. Horses with severe comminution of the middle phalanx were excluded.
      Three 5.5 mm cortical bone screws placed in lag fashion alone or in combination
      with a 4 or 3 hole dynamic compression plate affixed with 4.5 mm cortical bone
      screws were compared. A lower limb fibreglass cast was applied in all cases.
      Period in cast, time to return to intended use, complications encountered and
      outcome were evaluated. Seven of the 8 hindlimbs treated with the combination
      technique became sound. Three out of 6 of the front limbs treated with the
      combination technique became sound. Four of the 5 horses with hindlimbs, and one
      of the 2 with front limbs, treated with screws only returned to their intended
      use. The type of internal fixation did not appear to influence the overall number
      of horses returning to the intended level of performance. The period spent in
      cast and the time to return to soundness were decreased in horses operated on
      using the combination technique. We concluded that, in the immediate
      postoperative period, the combination of the parallel screw technique with a
      dorsally-applied dynamic compression plate provides the most stable and secure
      fixation, minimising motion, expediting bone remodelling and therefore favouring
      rapid fusion of that joint.

PMID- 11469769
TI  - A study of ten cases of focal peritarsal infection as a cause of severe lameness
      in the thoroughbred racehorse: clinical signs, differential diagnosis, treatment
      and outcome.
AB  - The differential diagnoses of tarsal joint infection, fracture and peritarsal
      focal infection are of particular importance in practice. The objective of the
      present report is to provide additional clinical data to assist in the
      understanding of one of these conditions. The haematological parameters, clinical
      signs, treatment and outcome of 10 cases of severe lameness associated with
      peritarsal infection are reviewed. All horses had a significant rise in rectal
      temperature. The majority of cases (6/10) had haematological changes consistent
      with acute bacterial infection on the day of first examination. In the remaining
      cases these changes were not apparent on a blood sample taken on the first
      examination, but became so after 24 h. Nine out of 10 cases made a complete
      recovery on a regimen of i.v. antibiotic therapy, in conjunction with
      administration of nonsteroidal anti-inflammatory drugs and repeated forced
      exercise. One case developed osteomyelitis of the third and fourth metatarsal
      bones, but made a full recovery in due course. It is concluded that, in the
      majority of cases, prompt treatment with antibiotic therapy, analgesics and
      forced exercise results in complete resolution of the condition.

PMID- 11469770
TI  - Recovery from transport and acclimatisation of competition horses in a hot humid
      environment.
AB  - The aims of the present field-based study were to investigate changes in fit
      horses undergoing acclimatisation to a hot humid environment and to provide data
      on which to base recommendations for safe transport and acclimatisation. Six
      horses (age 7-12 years) were flown from Europe to Atlanta and underwent a 16 day
      period of acclimatisation. Exercise conditions during acclimatisation (wet bulb
      globe temperature index 27.6+/-0.0 [mean +/- s.e.]) were more thermally stressful
      compared with the European climate from which the horses had come (22.0+/-1.8,
      P<0.001). Following the flight, weight loss was 4.1+/-0.8% bodyweight and took
      around 7 days to recover. Water intake during the day was significantly increased
      (P<0.05) compared with night during acclimatisation. Daily mean exercise duration
      was 72+/-12 min and the majority of work was performed with a heart rate below
      120 beats/min. Respiratory rate (fR) was increased (P<0.05) throughout
      acclimatisation compared with in Europe, but resting morning (AM) and evening
      (PM) rectal temperature (TREC), heart rate (fC) and plasma volume were unchanged.
      White blood cell (WBC) count was significantly increased at AM compared with in
      Europe on Days 4 and 10 of acclimatisation (P<0.01), but was not different by Day
      16. In conclusion, horses exposed to hot humid environmental conditions without
      prior acclimatisation are able to accommodate these stresses and, with
      appropriate management, remain fit and clinically healthy, without significant
      risk of heat illness or heat-related disorders, provided they are allowed
      sufficient time to recover from transport, acclimatisation is undertaken
      gradually and they are monitored appropriately.

PMID- 11469771
TI  - A cross-sectional study of colic in horses on thoroughbred training premises in
      the British Isles in 1997.
AB  - The aim of this study was to estimate the incidence of colic in horses in
      Thoroughbred training premises in 1997 in the British Isles. The seasonal pattern
      and outcome of colic episodes were also investigated, together with any
      association between premises level variables and colic. Data were collected by a
      postal questionnaire. The results showed a colic incidence density of 7.19/100
      horse years (s.e. 0.42) and a cumulative incidence of colic of 5.80% (s.e. 0.30).
      Premises were grouped according to whether they had more Flat than National Hunt
      horses (Flat premises) or more National Hunt than Flat horses (NH premises). A
      similar rate of colic episodes was found in each group. However, significantly
      higher cumulative incidences of one episode of colic were found in the Flat
      premises and of multiple episodes in the NH premises, respectively. The outcome
      of each episode of colic showed spontaneous recovery in 28.7%, medical recovery
      in 63.1%, surgical recovery in 2.0% and death in 6.2% of cases. This indicated an
      overall mortality rate from colic of 0.45 deaths/100 horse years. The seasonal
      pattern of episodes of colic showed a spring and autumn peak, with significant
      differences in the seasonal pattern between the Flat and NH premises. Relative
      risk analysis and logistic regression modelling with random effects showed
      significant associations between the number of episodes of colic and the number
      of horses on the premises (allowing for the number of horses on each premises,
      the larger premises had a decreased risk of colic). After adjusting for the
      number of horses, 3 other variables were associated with colic; Flat premises
      (with an increased risk), the owner being the sole person looking after the
      horses (a decreased risk) and the premises being a combined training and breeding
      establishment (a decreased risk).

PMID- 11469772
TI  - A comparison of the effects of local analgesic solution in the navicular bursa of
      horses with lameness caused by solar toe or solar heel pain.
AB  - We hypothesised that analgesia of the navicular bursa is not selective for the
      navicular apparatus; and that solar pain in some horses can be temporarily
      abolished or attenuated by analgesia of the navicular bursa. To test this
      hypothesis, we caused lameness in horses by inducing pain in the dorsal margin or
      the angles of the sole and then evaluated the ability of a local analgesic
      solution administered into the navicular bursa to attenuate lameness. The
      response of horses with solar pain in the dorsal or palmar aspect of the foot to
      3.5 ml local analgesic solution administered into the navicular bursa was
      examined. Lameness was induced in 6 horses by creating solar pain in the dorsal
      aspect of one forefoot and, at another time, the palmar aspect of the other
      forefoot, with set-screws inserted into a custom-made shoe. Horses were
      videotaped trotting before and after application of set-screws and after
      administering 3.5 ml local analgesic solution into the navicular bursa. Lameness
      scores were assigned by examining videotaped gaits. Scores were significantly
      lower (P<0.05) for all horses with set-screws applied to the dorsal margin of the
      sole after administration of local analgesic solution into the navicular bursa.
      In conclusion, analgesia of the navicular bursa was less effective in
      desensitising the angles of the sole than in desensitising the dorsal margin of
      the sole. Pain arising from the sole should not be excluded as a cause of
      lameness when lameness is attenuated by analgesia of the navicular bursa.

PMID- 11469773
TI  - Effect of dental correction on feed digestibility in horses.
AB  - To test the hypothesis that routine dental correction (removal only of sharp
      hooks and points from molars and premolars) would improve digestion of a
      hay/grain ration whereas performance 'floats' (rounding and smoothing of the
      dental arcades) would adversely affect digestion, 8 mature horses free from
      dental correction for over a year were used. Five-day digestion trials were
      conducted before and 2 and 4 weeks after correction in all horses. Although all
      horses had sharp points and minor premolar hooks, none had severe dental
      abnormalities. There were no significant differences found in apparent digestion
      of dry matter, crude protein, neutral detergent fibre or acid detergent fibre
      relative to precorrection data or controls (uncorrected horses on same digestion
      trial). Apparent digestibility of crude protein and fibre, however, was reduced
      if the occlusal angle of premolar 307 was greater than 80 degrees relative to the
      vertical axis (flattened). It should be recommended that regular dental
      correction be continued. However, if only small points and hooks are present,
      correction will not significantly improve digestion. Performance floating does
      not adversely affect digestion 2-4 weeks after the procedure is performed.
      Alterations in molar occlusal surface angle may affect digestibility of protein
      and fibre.

PMID- 11469774
TI  - Concentration of collagen, aggrecan and cartilage oligomeric matrix protein
      (COMP) in synovial fluid from equine middle carpal joints.
AB  - The aim of the present investigation was to study the metabolic activity of the
      third carpal bone and the release of COMP, aggrecan and collagen type II
      molecules in the synovial fluid as a result of injury. Cartilage oligomeric
      matrix protein (COMP), aggrecan and collagen type II or fragments of these
      molecules released to the synovial fluid and serum (COMP) were quantified in
      samples from 73 left equine middle carpal joints from 2 breeds with different
      activity profiles (52 Standardbred trotters [STB] and 21 Swedish Warmblood riding
      horses [SWH]) and different articular cartilage lesions. Synovial and serum
      samples were analysed using inhibition ELISA for COMP and aggrecan. An ELISA that
      combines features of both the competitive and capture ELISAs was used for
      collagen type II. COMP and aggrecan concentrations decreased in synovial fluid
      from the joints with moderate lesions of STB compared with the normal joints;
      COMP from 16.6 to 12.0 microg/ml and aggrecan from 93.0 to 68.1 microg/ml. In
      serum, COMP concentrations were also lowered in the STB with moderate lesions
      compared with the normal joints, while in the SWH, the COMP concentration in
      synovial fluids from joints with moderate lesions was somewhat increased at 19.6
      microg/ml compared with the normal joints (17.6 microg/ml). The ratio between
      aggrecan/COMP in the synovial fluid from joints with moderate lesions was higher
      in the STB (6.2) than in the SWH (3.4). The level of collagen type II in synovial
      fluid was higher in the SWH (8.8 microg/ml) than the STB (1.6 microg/ml), but
      there was no correlation between joint damage and collagen concentrations in
      synovial fluids (10.0 and 1.8 microg/ml in joints with moderate lesions from SWH
      and STB, respectively). A marked difference in COMP synthesised upon metabolic
      labelling between the normal and osteoarthritic cartilage was seen and the
      synthesis of COMP in the articular cartilage of the third carpal bone with
      moderate articular lesions (from an STB) was lower than in the joint with mild
      lesions. This difference between breeds may reflect different load characters, in
      release of macromolecules in osteoarthritic and normal joints. This a novel
      finding that should be considered in studies of equine traumatic arthritis.

PMID- 11469775
TI  - A prospective study of the roles of clostridium difficile and enterotoxigenic
      Clostridium perfringens in equine diarrhoea.
AB  - Faecal samples from adult horses and from foals with diarrhoea or with normal
      faeces were evaluated for the presence of Clostridium difficile, C. difficile
      toxins, C. perfringens enterotoxin (CPE) and C. perfringens spore counts.
      Clostridium difficile was isolated from 7/55 horses (12.7%) and 11/31 foals
      (35.5%) with colitis, but from 1/255 normal adults (0.4%) and 0/47 normal foals
      (P<0.001). Clostridium difficile toxins A and/or B were detected in 12/55
      diarrhoeic adults (21.8%) and 5/30 diarrhoeic foals (16.7%) but in only 1/83
      adults (1.2%) and 0/21 foals with normal faeces (P<0.001 and P<0.05,
      respectively). Clostridium perfringens enterotoxin was detected in 9/47
      diarrhoeic adults (19%) and 8/28 diarrhoeic foals (28.6%), but was not detected
      in 47 adult horses (P<0.002) or 4 foals (P = 0.22) with normal faeces. The
      positive predictive value of isolation of C. perfringens with respect to the
      presence of CPE was only 60% in adult horses and 64% in foals. There was no
      association between total C. perfringens spore count and CPE in the faeces. The
      overall mortality rate from colitis was 22% for adult horses and 18% for foals.
      Clostridium difficile toxin-positive adult horses with colitis were less likely
      to survive than C. difficile-negative horses with colitis (P = 0.03). This study
      provides further evidence that C. difficile and enterotoxigenic C. perfringens
      are associated with equine enterocolitis.

PMID- 11469776
TI  - Joint moments in the distal forelimbs of jumping horses during landing.
AB  - Tendon injuries are an important problem in athletic horses and are probably
      caused by excessive loading of the tendons during demanding activities. As a
      first step towards understanding these injuries, the tendon loading was
      quantified during jump landings. Kinematics and ground reaction forces were
      collected from the leading and trailing forelimbs of 6 experienced jumping
      horses. Joint moments were calculated using inverse dynamic analysis. It was
      found that the variation of movement and loading patterns was small, both within
      and between horses. The peak flexor joint moments in the coffin and fetlock
      joints were larger in the trailing limb (-0.62 and -2.44 Nm/kg bwt, respectively)
      than in the leading limb (-0.44 and -1.93 Nm/kg bwt, respectively) and exceeded
      literature values for trot by 82 and 45%. Additionally, there was an extensor
      coffin joint moment in the first half of the stance phase of the leading limb
      (peak value 0.26+/-0.18 Nm/kg bwt). From these results, it was concluded that the
      loading of the flexor tendons during landing was higher in the trailing than in
      the leading limb and that there was an unexpected loading of the extensor tendon
      in the leading limb.

PMID- 11469777
TI  - Effects of phlebotomy on haemodynamic characteristics during exercise in
      standardbred trotters with red cell hypervolaemia.
AB  - Five Standardbred trotters with red cell hypervolaemia (RCHV) were compared
      before and after removal of approximately 22% (36 ml/kg bwt) of the total blood
      volume in order to evaluate the haemodynamic responses, haemorheological
      alterations and oxygen transport during exercise to fatigue. Data were recorded
      during submaximal exercise at 4 different speeds on a treadmill and then during
      continued running at the highest speed step until fatigue. Oxygen uptake (VO2),
      pulmonary artery pressure (PAP), systemic artery pressure (SAP), heart rate (HR),
      haematocrit and haemoglobin concentrations (Hb) were measured. Arteriovenous O2
      content difference (C(a-v)O2), pulmonary vascular resistance (PVR) and total
      systemic resistance (TSR) were calculated. Whole blood and plasma viscosity and
      erythrocyte aggregation tendency were determined with a rotational viscometer.
      Endoscopy was performed after exercise. ANOVA was used for statistical analysis.
      Phlebotomy resulted in a decrease in haematocrit and Hb during the course of
      exercise. Blood and plasma viscosity were lower and erythrocyte aggregation
      tendency was higher after phlebotomy. Throughout exercise, including submaximal
      work and continued running to fatigue, PAP, SAP, PVR, TSR and C(a-v)O2 were lower
      after phlebotomy. HR was higher after phlebotomy during submaximal exercise.
      Oxygen delivery and VO2 were lower after phlebotomy in the period from submaximal
      exercise to fatigue. Run time to fatigue was shorter after phlebotomy. Four
      horses showed exercise-induced pulmonary haemorrhage (EIPH) before phlebotomy and
      the degree of bleeding was diminished but not abolished after phlebotomy. The
      reductions in PVR, TSR, PAP and SAP after phlebotomy were probably a result of
      reduced blood viscosity. In conclusion, although a 22% reduction in blood volume
      improved the haemodynamic and haemorheological parameters and the degree of EIPH,
      it was found that RCHV trotters have to rely on high oxygen delivery to the
      working muscles for maintenance of maximal performance.

PMID- 11469778
TI  - Water-soluble treatments to enhance glucose permeability of protein-resistant
      polymer overlayers.
AB  - This study employed two water-soluble and nontoxic molecules, sucrose and
      glycerol, to enhance the permeability of PEG-PHEMA polymer gels coated onto 100
      kDa molecular weight cutoff polyethersulfone (PES) microdialysis probes. Sucrose
      precoating of the probes prior to prepolymer coating prevented penetration of the
      prepolymer into the microdialysis membrane. Glycerol mixed with the prepolymer
      introduced porosity in the polymer coating upon curing. The sucrose and glycerol
      were completely removed by soaking in PBS after curing of the polymer coat on the
      probe tip. Polymer coated probe glucose permeability was tested by measuring
      glucose recovery from PBS solutions. Biocompatibility was assessed by measuring
      glucose recovery of polymer coated probes from heparanized whole porcine blood.
      Results show that the sucrose and glycerol treatments yielded polymer coated
      probes with glucose permeability nearly equal to bare probes when tested in PBS
      solution, but that this increased permeability was not observed when tested in
      whole blood. This suggests that the thickness of the polymer films (10-100
      microm), while not a limiting factor in PBS solution, may have presented a
      diffusion barrier to glucose recovered from blood. Surprisingly, however, the
      polymer coated probes exhibited less thrombus formation that did the bare probes
      after blood exposure.

PMID- 11469779
TI  - Fibronectin purification from human plasma in a packed-bed column system with
      gelatin immobilized PHEMA microspheres.
AB  - Bioaffinity chromatography has a unique and powerful role that is used as a
      purification tool in the production of therapeutic plasma protein derivatives. In
      this study, a bioaffinity-ligand, i.e. gelatin, was covalently immobilized with
      PHEMA microspheres (150-200 microm in diameter). The affinity sorbent carrying
      7.5 mg gelatin g(-1) polymer was then used to separate fibronectin from human
      plasma in a packed-bed column system. Fibronectin separation from human plasma on
      unmodified PHEMA microspheres was 0.45 mg g(-1), while much higher adsorption
      values, up to 21.8 mg g(-1), were obtained with gelatin-immobilized microspheres.
      The fibronectin adsorption capacity of the microspheres decreased with an
      increase in the recirculation rate of plasma. Fibronectin adsorption increased
      with decreasing temperature, and the maximum adsorption achieved at 4 degrees C
      (26.3 mg fibronectin g(-1)). Up to 94.7% of the adsorbed fibronectin was desorbed
      by using 2 M urea in the presence of 1 M sodium chloride as elution agent. The
      adsorption-desorption cycle was repeated ten times using the same affinity
      column. There was no remarkable reduction in the adsorption capacity of the
      gelatin-immobilized PHEMA microspheres.

PMID- 11469780
TI  - Degradation and drug delivery properties of poly(1,4-cyclohexanedicarboxylic
      anhydride).
AB  - Polyanhydrides for drug-controlled release systems from cis- and trans-1,4
      cyclohexanedicarboxylic acid (1,4-CHDA) were synthesized by melt
      polycondensation. The degradation of polymers was estimated by weight loss in 0.1
      mol l(-1), pH 7.4 phosphate buffer at 37 degrees C. The drug delivery was
      conducted in the same buffer. The results show that the different polymers lost
      weight over 150-360 h, and fine surface erosion was investigated. The different
      conformation of CHDA has an obvious influence on the degradation of
      polyanhydrides due to their different crystallinity, with higher crystallinity
      samples degrading much more slowly. The incorporation of adipic acids into the
      poly(CHDA) can obviously accelerate the degradation and the introduction of -CH2-
      segments increased the flexibility of polyanhydride backbone and accelerated the
      degradation rate. In vitro delivery experiments show that Bruffen was completely
      released in about 10 days from a melting mold disk with a fine linear delivery
      curve.

PMID- 11469781
TI  - Free electron laser induces specific immobilization of heparin on polysulfone
      films.
AB  - Covalent immobilization of heparin has been developed to reduce the amount of
      heparin administered systematically during long-term dialysis. Recently, it was
      doubted partially because of the complexion during immobilization process. In
      this study, we investigated a novel method for specific immobilization of heparin
      on polysulfone (PSF) via free electron laser (FEL) irradiation. Laser wavelengths
      of 6.18 or 6.31 microm, the typical absorption bands of carboxyl groups of
      heparin and aromatic rings in PSF, respectively, were chosen to irradiate the
      thin heparin membrane formed on PSF surfaces. The amount of heparin immobilized
      on PSF was measured by the toluidine blue method. The binding of heparin on PSF
      was analyzed by X-ray photoelectron spectroscopy (XPS). The immobilization of
      heparin resulted in a hydrophilic surface on which decreased platelet adhesion
      was observed. The efficiency differences, depending on laser wavelengths, were
      discussed from the point of view of structural and environmental differences of
      light-absorbing groups.

PMID- 11469782
TI  - Modification of gold surface by grafting of poly(ethylene glycol) for reduction
      in protein adsorption and platelet adhesion.
AB  - Gold surfaces were first treated in an alkanethiol solution to form self
      assembled monolayers (SAMs). The thiolated Au surface was then subjected to Ar
      plasma pretreatment, followed by air exposure and UV-induced graft polymerization
      of poly(ethylene glycol) methacrylate (PEGMA) macromonomer. In comparison with
      the 3-mercaptopropionic acid-2-ethylhexyl ester (MPAEE) SAM, the (3
      mercaptoproply)trimethoxysilane (MPTMS) SAM on Au exhibited higher stability
      under the conditions of Ar plasma pretreatment. The graft concentration of the
      PEGMA polymer on SAM-modified Au surface increased with increasing PEGMA
      macromonomer concentration and UV-graft polymerization time. The modified-Au
      surfaces were characterized by X-ray spectroscopy (XPS), atomic force microscopy
      (AFM), and water contact angle measurement. The Au surface with a high
      concentration of grafted PEGMA polymer could completely repel protein adsorption
      and platelet adhesion.

PMID- 11469783
TI  - Gas transfer and blood compatibility of asymmetric polyimide hollow fiber.
AB  - We have fabricated an asymmetric polyimide hollow fiber for use as a membrane
      oxygenator. A dry/wet phase inversion process has been applied to a spinning
      process to prepare the hollow fiber. The fiber structure consisted of a complete
      defect-free skin layer and a porous substructure characterized by the presence of
      an open-cell structure and macrovoids. The outer diameter was 480 microm with a
      wall thickness of 50 microm. Transfer rates of O2 and CO2 in the asymmetric
      polyimide fiber were 2.3 x 10(-5) and 1.1 x 10(-4) (cm3 (STP)/(cm2 s cmHg)),
      respectively, which were four times higher than those measured in the
      polydimethylsiloxane (PDMS) fiber of the presently-available membrane oxygenator.
      The (QO2/QN2) selectivity of the polyimide fiber was 4.9, indicating that the
      surface skin layer is essentially defect-free. The blood compatibility of the
      polyimide hollow fiber has been evaluated in vitro and in vivo. The polyimide had
      an excellent blood compatibility when compared with PDMS.

PMID- 11469784
TI  - Surface characterization and platelet compatibility evaluation of surface
      sulfonated chitosan membrane.
AB  - The effect of various sulfonated derivatives of chitosan on platelet activation
      and blood coagulation was examined. The surface properties of artificial
      biomaterials have been thought as the key factors which mediate the interactions
      between the biological environment and biomaterial itself. In this study, the
      sulfonation was directly performed on the chitosan membrane surface. The chitosan
      membrane was surface-sulfonated by reactions with sulfur-pyridine trioxide
      complex (SO3/pyridine) in H2O solution and N,N-sulfur-dimethylformamide trioxide
      complex (SO3/DMF) in DMF. Blood compatibility was evaluated by an in vitro
      platelet adhesion assay. The surface reaction of SO3/pyridine in aqueous acid
      medium yields N,O-sulfated chitosan with cationic NH3+ groups. After
      neutralization, this surface has been shown to induce a low degree of platelet
      adhesion and activation. When the surface-sulfonation is performed in an aqueous
      alkaline medium, although the degree of sulfonation is lower than the samples
      above, the N-sulfated chitosan significantly reduced the adhesion and activation
      of platelets. For the acidic SO3/DMF reaction system, N,O-sulfated chitosan was
      obtained with a high extent of sulfonation and cationic NH3+ groups. On this
      surface fully spread platelets and some platelet aggregates were found instead.
      This may be attributed to the ionic interactions between the platelets membrane
      surface and the cationic groups on the modified chitosan membrane.

PMID- 11469785
TI  - Biodegradable biocomposite non-woven matrices based on PDLLA- and elastin
      solubilized proteins/elastin.
AB  - Poly(D,L-lactide) (PDLLA) was synthesized by ring-opening polymerization of D,L
      lactide. Non-woven PDLLA matrices were prepared by an extrusion/winding process.
      The process conditions were optimized and the surfaces of these matrices were
      modified by glow-discharge treatment and/or glutaraldehyde incorporation for
      immobilization of elastin-derived proteins (ESP) to the matrix to increase the
      biocompatibility and also to improve the bioactivity of the matrix. Glow
      discharge conditions were optimized. Ethylene diamine (EDA) and Ar were used as
      the active monomers in the plasma phase. When EDA was used, the glow-discharge
      treated PDLLA matrices were first allowed to be reacted with glutaraldehyde,
      although, when Ar used, the treated matrices were used directly for ESP
      immobilization. The higher degree of immobilization was obtained for EDA and
      glutaraldehyde. The ESP-incorporated PDLLA matrices were further treated with
      elastin by cross-reaction of the ESP molecules on the matrix surfaces with
      elastin. Scanning electron microscopy (SEM) studies showed that ESP were
      homogeneously deposited the surface of the matrix.

PMID- 11469787
TI  - Antimicrobial peptide buforin I inhibits tissue factor-initiated coagulation.
AB  - The enhanced extrinsic blood coagulation following septic shock often manifests
      cardiovascular complications. The upregulated monocytic tissue factor (mTF) was
      shown to be a primary contributor to the extrinsic hypercoagulation following
      acute bacterial endotoxin (LPS) infection. A single-stage clotting assay monitors
      TF-initiated coagulation. We herein demonstrate a novel anticoagulant activity of
      antimicrobial peptide Buforin I (BF I) in offsetting LPS-induced mTF
      hypercoagulation in THP-1 cells, which was confirmed in a cell-free in vitro
      model, showing that BF I effectively blocked rabbit brain thromboplastin (rbTF)
      procoagulant activity. Upon inclusion of 25 microM BF I into human plasma, the
      prolonged prothrombin time (PT) was consistent with the depressed TF-initiated
      coagulation. In a two-stage chromogenic assay monitoring S-2288 hydrolysis, BF I
      significantly inhibited not only mTF- but also rbTF-catalyzed FVII activation
      accompanied by the diminished FVIIa formation. The inhibition by BF I of FVII
      activation accounted for its novel anticoagulant activity in offsetting mTF
      initiated hypercoagulation.

PMID- 11469788
TI  - Hydrogen peroxide damages the zinc-binding site of zinc-deficient Cu,Zn
      superoxide dismutase.
AB  - Mutations in Cu,Zn superoxide dismutase (Cu,Zn SOD) account for approximately 20%
      of cases of familial amyotrophic lateral sclerosis (ALS), a late-onset
      neurodegenerative disease affecting motor neurons. These mutations decrease
      protein stability and lower zinc affinity. Zinc-deficient SOD (Cu,E SOD) has
      altered redox activities and is toxic to motor neurons in vitro. Using bovine
      SOD, we studied the effects of hydrogen peroxide (H(2)O(2)) on Cu,E SOD and Cu,Zn
      SOD. Hydrogen peroxide treatment of Cu,E SOD inactivated zinc binding activity
      six times faster than superoxide dismutase activity, whereas inactivation of
      dismutase activity occurred at the same rate for both Cu,Zn SOD and Cu,E SOD.
      Zinc binding by Cu,E SOD was also damaged by simultaneous generation of
      superoxide and hydrogen peroxide by xanthine oxidase plus xanthine. Although
      urate, xanthine, and ascorbate can protect superoxide dismutase activity of Cu,Zn
      SOD from inactivation, they were not effective at protecting Cu,E SOD. Hydrogen
      peroxide induced subtle changes in the tertiary structure but not the secondary
      structure of Cu,E SOD as detected by near and far UV circular dichroism. Our
      results suggest that low levels of hydrogen peroxide could potentially enhance
      the toxicity of zinc deficient SOD to motor neurons in ALS by rendering zinc loss
      from SOD irreversible.

PMID- 11469789
TI  - Calcitroic acid is a major catabolic metabolite in the metabolism of 1 alpha
      dihydroxyvitamin D(2).
AB  - Calcitroic acid (1 alpha-hydroxy-23 carboxy-24,25,26,27-tetranorvitamin D(3)) is
      known to be the major water-soluble metabolite produced during the deactivation
      of 1 alpha,25-dihydroxyvitamin D(3). This deactivation process involves a series
      of oxidation reactions at C(24) and C(23) leading to side-chain cleavage and,
      ultimately, formation of the calcitroic acid. Like 1 alpha,25-dihydroxyvitamin
      D(3), 1 alpha,25-dihydroxyvitamin D(2) is also known to undergo side-chain
      oxidation; however, to date there has been no evidence suggesting that 1 alpha,25
      dihydroxyvitamin D(2) undergoes side-chain cleavage. To investigate this
      possibility, we studied 1 alpha,25-dihydroxyvitamin D(2) metabolism in HPK1A-ras
      cells as well as the well characterized perfused rat kidney system. Lipid and
      aqueous-soluble metabolites were prepared for characterization. Aqueous-soluble
      metabolites were subjected to reverse-phase HPLC analysis. The major aqueous
      soluble metabolite from both the kidney and cell incubations comigrated with
      authentic calcitroic acid on two reverse-phase HPLC columns of different
      chemistry. The putative calcitroic acid from the cell and kidney incubations was
      methylated and found to comigrate with methylated authentic standard on straight
      phase and reverse-phase HPLC columns. The identity of the methylated metabolite
      from cell incubations was also confirmed by mass spectral analysis. These data
      show, for the first time, that calcitroic acid is a major terminal product for
      the deactivation of 1 alpha,25-dihydroxyvitamin D(2). Intermediates leading to
      the formation of the calcitroic acid in the 1 alpha,25-dihydroxyvitamin D(2)
      metabolism pathway are currently being studied.

PMID- 11469790
TI  - Primary structure, isoforms, and molecular modeling of a chitin-binding mistletoe
      lectin.
AB  - From mistletoe Viscum album L. extracts three chitin-binding lectin isoforms,
      cbML1, cbML2, and cbML3, were isolated and their primary structure determined.
      All three cbML isoforms are composed of two protein chains of 48 or 49 amino acid
      residues, linked by an intermolecular disulfide bond. The sequence of each single
      cbML chain is characterized by a relatively high number of cysteine and glycine
      residues, 9 and 6, respectively, and contains four intramolecular disulfide
      bridges. On the basis of the combined interpretation of sequencing and MALDI MS
      data, the following results for the three cbML isoforms were obtained: the first
      one consists of two identical truncated polypeptide chains (1--48), the second is
      a heterodimer, containing one truncated (1--48) and one full-length chain (1-
      49), and the third is composed of two full length chains (1--49). The cbML
      sequence shows 55% identity to hevein, a single-chain chitin-binding protein of
      43 amino acids, one of the most predominant proteins in natural rubber latex. On
      the basis of the NMR data on hevein from Hevea brasiliensis the three-dimensional
      structure of cbML3 was modelled. The 26 sequence changes between cbML3 and hevein
      were accommodated with only little perturbation in the main chain folding. A
      comparison of the primary structures of cbML3 and hevein is shown and the effects
      of the sequence changes are discussed. Differences have been identified in the
      loop region of the molecule and the potential interface region of cbML3
      supporting the dimer formation. The high-affinity chitin-binding site seems to be
      highly conserved.

PMID- 11469791
TI  - Cellular characterization of leukotoxin diol-induced mitochondrial dysfunction.
AB  - Leukotoxin, a cytochrome P450-derived epoxide of linoleic acid, has been
      implicated as a causative factor in acute respiratory distress syndrome.
      Conversion of this fatty acid epoxide to leukotoxin diol by epoxide hydrolase has
      been hypothesized as the critical activation step in leukotoxin-induced cellular
      toxicity. In both human and insect cells, we observed that leukotoxin diol causes
      acute cellular toxicity and that cyclosporin A, an inhibitor of the mitochondrial
      permeability transition, ameliorates leukotoxin diol-associated toxicity. To
      evaluate mitochondria as a target of leukotoxin diol, multiple aspects of
      mitochondrial integrity were evaluated in both cell- and organelle-based assays.
      Leukotoxin diol specifically activated the mitochondrial permeability transition,
      resulting in release of cytochrome c and subsequent cell death. Pretreatment with
      cyclosporin A inhibited these effects and, furthermore, limited in vivo toxicity.
      While the mechanisms underlying leukotoxin-mediated toxicity remain to be fully
      elucidated, the observation that leukotoxin diol disrupts mitochondrial function
      specifically through activation of the mitochondrial permeability transition
      suggests at least one mechanism through which leukotoxin diol may exert its
      activity in physiological contexts.

PMID- 11469792
TI  - Synthesis and mobilization of glycogen during metamorphosis of the medfly
      Ceratitis capitata.
AB  - There are no recent reports focusing on insect glycogen metabolism that take the
      advances made in mammalian and yeast systems into account. Moreover, little is
      known about glycogen synthesis and degradation during insect metamorphosis. The
      biosynthesis and mobilization of insect glycogen were measured during the larva
      to adult transition in the Medfly, Ceratitis capitata. The glycogen accumulated
      by larva decreased to reach almost undetectable levels at the beginning of the
      pupation process. Histological preparations of 40 h muscles and fat body
      confirmed a low glycogen content, in contrast with high glycogen images in third
      larva tissues. After 40 h, glycogen was synthesized de novo and accumulates up to
      adult ecdysis. We obtained the metamorphosis-dependent profiles of phosphorylase,
      glycogen synthase, and a glycogenin-like protein. This novel insect glycogen
      initiator protein (the first measured in an arthropod) appeared to be similar to
      the homologous enzymes from vertebrates and yeast. We have correlated these
      results with other biochemical events and anatomical landmarks to understand the
      use of storage carbohydrates during the sequence of metamorphosis events.

PMID- 11469793
TI  - Yeast COQ4 encodes a mitochondrial protein required for coenzyme Q synthesis.
AB  - The COQ4 gene coding for a component of the coenzyme Q biosynthetic pathway in
      the yeast Saccharomyces cerevisiae was cloned by a functional complementation of
      a Q-deficient mutant strain. Yeast coq4 mutant strains harboring the COQ4 gene on
      either single- or multicopy plasmids acquired the ability to grow on media
      containing a nonfermentable carbon source, synthesize Q(6), and respire. COQ4
      encodes a polypeptide containing 335 amino acids with a calculated molecular mass
      of 38.6 kDa. By Western blot analysis with a specific antiserum, Coq4p was shown
      to peripherally associate with the matrix face of the mitochondrial inner
      membrane. The putative mitochondrial-targeting sequence present at the amino
      terminus of the polypeptide efficiently imported it to mitochondria in a membrane
      potential-dependent manner. Steady-state levels of COQ4 mRNA were increased
      during growth on glycerol-containing medium, in accordance with a function in Q
      biosynthesis. The function of Coq4p is unknown, although its presence is required
      to maintain a steady-state level of Coq7p, another component of the Q
      biosynthetic pathway. The results presented here, along with those available from
      literature, are discussed in light of the recently proposed existence of a
      multisubunit complex functioning in Q biosynthesis (A. Y. Hsu, T. Q. Do, P. T.
      Lee, and C. F. Clarke, 2000, Biochim. Biophys. Acta 1484, 287-297).

PMID- 11469794
TI  - Effect of alpha-methyldopa on pentoxyresorufin O-dealkylation in liver microsomes
      from rats treated with phenobarbital.
AB  - Loss of pentoxyresorufin O-dealkylation (PROD) was observed when microsomes from
      PB-treated rats were preincubated in the presence of NADPH. PROD proved to be
      quite sensitive towards inactivation. Decrease in cytochrome P450 (CYP) dependent
      activity was accompanied by simultaneous formation of thiobarbituric acid
      reactive substances (TBARS) indicating the occurrence of lipid peroxidation. The
      presence of 50 microM alpha-methyldopa (AMD) during preincubation with NADPH
      resulted in complete protection against enzyme activity loss and the extent of
      lipid peroxidation was also diminished. Addition of ascorbate or GSH in
      combination with AMD reduced the protective effect of the drug on PROD. AMD
      probably exerts its effect by scavenging reactive oxygen species but chelation of
      ferric ions can also contribute to the protective effect of the drug on PROD
      activity.

PMID- 11469795
TI  - Polyunsaturated fatty acids promote 8-hydroxy-2-deoxyguanosine formation through
      lipid peroxidation under the glutamate-induced GSH depletion in rat glioma cells.
AB  - It has been reported that glutamate decreased the intracellular glutathione (GSH)
      concentration and thereby induced cell death in C6 rat glioma cells.
      Polyunsaturated fatty acids such as arachidonic acid, gamma-linolenic acid, and
      linoleic acid enhanced lipid peroxidation promoting 8-hydroxy-2'-deoxyguanosine
      (8-OH-dG) formation under the glutamate-induced GSH-depletion. The enhancement of
      lipid peroxidation by polyunsaturated fatty acids was species-dependent. Some
      antioxidants capable of scavenging oxygen and lipid radicals and some iron or
      copper scavengers inhibited both the lipid peroxidation and the 8-OH-dG
      formation, consequently protecting against cell death induced by glutamate
      induced GSH depletion. These results suggest that GSH depletion caused by
      glutamate induces lipid peroxidation and consequently 8-OH-dG formation and that
      polyunsaturated fatty acids enhance lipid peroxidation associated with mediated 8
      OH-dG formation through a chain reaction.

PMID- 11469796
TI  - Structure--function relationships of rat hepatic tryptophan 2,3-dioxygenase:
      identification of the putative heme-ligating histidine residues.
AB  - The liver cytosolic enzyme tryptophan 2,3-dioxygenase (TDO) catalyzes the
      oxidation of L-tryptophan to formylkynurenine and controls the physiological flux
      of tryptophan into both the serotonergic and kynureninic pathways. This
      hemoprotein enzyme is composed of four noncovalently bound subunits of equivalent
      mass and contains two heme moieties per molecule. Electron paramagnetic resonance
      analyses have indicated that a histidyl nitrogen is involved in heme ligation
      [Henry et al., (1976) J. Biol. Chem. 251, 1578], but the identity of the His
      residue(s) is unknown. In an attempt to characterize the active site of the
      enzyme we have substituted each of the 12 His residues in the rat TDO subunit
      with Ala, to determine their relative importance in heme binding. Sequence
      alignment of the rat liver protein with that of known or putative TDO sequences
      from other organisms reveals that four of the His residues are conserved in
      eukaryotes, two of which are also conserved in prokaryotes. Our findings indicate
      that replacement of the evolutionarily conserved His 76 and 328 residues resulted
      in a dramatic reduction of TDO activity, whereas that of the eukaryotically
      conserved His70 resulted in a significant reduction relative to that of the wild
      type enzyme. On the other hand, replacement of the other eukaryotically conserved
      His273 residue, while affecting the relative expression of the enzyme, had little
      effect on its specific activity. Size-exclusion analyses revealed that the
      His76Ala and His328Ala mutants retained little or no heme, suggesting that these
      may be key residues in ligating the prosthetic heme moieties. Whether these His
      residues are both provided by the same TDO subunit or a different TDO subunit
      remains to be determined.

PMID- 11469797
TI  - The widespread effect of beta 1,4-galactosyltransferase on N-glycan processing.
AB  - We investigated beta 1,4-GalT (UDP-galactose: beta-d-N-acetylglucosaminide beta
      1,4-galactosyltransferase) in terms of intracellular competition with GnT-IV (UDP
      N-acetylglucosamine: alpha1,3-d-mannoside beta1,4-N
      acetylglucosaminyltransferase) and GnT-V (UDP-N-acetylglucosamine: alpha1,6-d
      mannoside beta 1,6-N-acetylglucosaminyltransferase). The beta 1,4-GalT-I gene was
      introduced into Chinese hamster ovary (CHO) cells producing human interferon
      (hIFN)-gamma (IM4/V/IV cells) and five clones expressing various levels of beta
      1,4-GalT were isolated. As we previously reported, parental IM4/V/IV cells
      express high levels of GnT-IVa and -V and produce hIFN-gamma having primarily
      tetraantennary sugar chains. The branching of sugar chains on hIFN-gamma was
      suppressed in the beta 1,4-GalT-enhanced clones to a level corresponding to the
      intracellular activity of beta 1,4-GalT relative to GnTs. Moreover, the contents
      of hybrid-type and high-mannose-type sugar chains increased in these clones. The
      results showed that beta 1,4-GalT widely affects N-glycan processing by competing
      with GnT-IV, GnT-V, and alpha-mannosidase II in cells and also by some other
      mechanisms that suppress the conversion of high-mannose-type sugar chains to the
      hybrid type.

PMID- 11469798
TI  - Purification and characterization of N-acetylglucosaminyl sulfotransferase from
      chick corneas.
AB  - N-Acetylglucosaminyl(GlcNAc) sulfotransferase, which transfers sulfate from
      adenosine 3'-phosphate 5'-phosphosulfate to GlcNAc at the nonreducing end of
      oligosaccharides, was purified 887-fold with a 8.4% yield from 2-day-old chick
      corneas by chromatography on CM-Sepharose, WGA-agarose, GlcNAc-agarose, and 3',5'
      ADP-agarose columns. The purified enzyme has an optimum pH of 6.0 (Mes buffer)
      and specifically transfers a sulfate to GlcNAc at the nonreducing end but not to
      internal GlcNAc. The enzyme was stimulated by protamine and Mn(2+). SDS
      polyacrylamide gel electrophoresis of the purified enzyme still showed two main
      bands (66 and 55 kDa) with some minor bands. It appears that this enzyme competes
      with beta-galactosyltransferase in binding to the nonreducing GlcNAc residue on
      KS synthesis; this suggests that the sulfation of the GlcNAc residue is coupled
      with the elongation of the KS chain.

PMID- 11469799
TI  - Proteolytic processing of the human T-cell lymphotropic virus 1 reverse
      transcriptase: identification of the N-terminal cleavage site by mass
      spectrometry.
AB  - Human T-cell lymphotropic virus 1 (HTLV-1) is a type C human retrovirus, which is
      the causative agent of Adult T-cell Leukemia and other diseases. The reverse
      transcriptase of HTLV-1 (E.C. 2.7.7.49) is synthesized as part of a Gag--Pro--Pol
      precursor protein, and the mature Gag, Pro, and Pol proteins, including the
      reverse transcriptase, are created by proteolytic processing catalyzed by the
      viral protease. The location of the proteolytic cleavage site, which creates the
      N-terminus of mature HTLV-1 reverse transcriptase, has not been previously
      identified. By using sequence comparisons of several retroviral polymerases, as
      well as information about the location of the ribosomal frameshift, we
      tentatively identified this N-terminal processing site. PCR amplification was
      used to construct a clone, which spans a region of the pro--pol junction of HTLV
      1, to produce a recombinant Pro--Pol protein spanning the locations of those
      cleavage sites proposed by others as well as the one identified by our sequence
      alignment. Cleavage of the recombinant Pro--Pol protein by HTLV-1 protease
      generated a 5.5-kDa fragment. Analysis of this fragment by capillary LC-MS and
      MS/MS revealed the N-terminal cleavage site to be between Leu(147)--Pro(148) of
      the pro ORF. This is the first physical identification of the authentic amino
      acid sequence of the reverse transcriptase of HTLV-1. The data reported here
      provides a basis for further investigation of the function and structural aspects
      of protein-nucleic interaction.

PMID- 11469800
TI  - Thioredoxin peroxidase-1 (peroxiredoxin-1) is increased in thioredoxin-1
      transfected cells and results in enhanced protection against apoptosis caused by
      hydrogen peroxide but not by other agents including dexamethasone, etoposide, and
      doxorubicin.
AB  - Thioredoxin-1 (Trx-1) is a small redox oncoprotein whose expression is increased
      in a number of human primary cancers where it is associated with aggressive tumor
      growth, inhibition of apoptosis and decreased patient survival. We report that
      Trx-1-transfected MCF-7 human breast cancer cells have increased expression of
      thioredoxin peroxidase-1 (TrxP-1) a peroxiredoxin family member that scavenges
      H(2)O(2) using Trx-1 as a source of reducing equivalents. Our work shows that
      TrxP-1 is more effective than selenium-dependent glutathione peroxidase in
      protecting cells against H(2)O(2) damage. Transfection of mouse WEHI7.2 lymphoma
      cells with human TrxP-1 or TrxP-2, but not TrxP-4, protects the cells against
      H(2)O(2) induced apoptosis but does not protect against apoptosis induced by
      dexamethasone, etoposide, or doxorubicin. The results show that an increase in
      TrxP-1 expression contributes to the protection against H(2)O(2) induced
      apoptosis caused by Trx-1, but does not protect against apoptosis induced by
      other agents.

PMID- 11469801
TI  - Flavin specificity and subunit interaction of Vibrio fischeri general NAD(P)H
      flavin oxidoreductase FRG/FRase I.
AB  - Apoenzyme of the major NAD(P)H-utilizing flavin reductase FRG/FRase I from Vibrio
      fischeri was prepared. The apoenzyme bound one FMN cofactor per enzyme monomer to
      yield fully active holoenzyme. The FMN cofactor binding resulted in substantial
      quenching of both the flavin and the protein fluorescence intensities without any
      significant shifts in the emission peaks. In addition to FMN binding (K(d) 0.5
      microM at 23 degrees C), the apoenzyme also bound 2-thioFMN, FAD and riboflavin
      as a cofactor with K(d) values of 1, 12, and 37 microM, respectively, at 23
      degrees C. The 2-thioFMN containing holoenzyme was about 40% active in specific
      activity as compared to the FMN-containing holoenzyme. The FAD- and riboflavin
      reconstituted holoenzymes were also catalytically active but their specific
      activities were not determined. FRG/FRase I followed a ping-pong kinetic
      mechanism. It is proposed that the enzyme-bound FMN cofactor shuttles between the
      oxidized and the reduced form during catalysis. For both the FMN- and 2-thioFMN
      containing holoenzymes, 2-thioFMN was about 30% active as compared to FMN as a
      substrate. FAD and riboflavin were also active substrates. FRG/FRase I was shown
      by ultracentrifugation at 4 degrees C to undergo a monomer-dimer equilibrium,
      with K(d) values of 18.0 and 13.4 microM for the apo- and holoenzymes,
      respectively. All the spectral, ligand equilibrium binding, and kinetic
      properties described above are most likely associated with the monomeric species
      of FRG/FRase I. Many aspects of these properties are compared with a structurally
      and functionally related Vibrio harveyi NADPH-specific flavin reductase FRP.

PMID- 11469802
TI  - alpha(1D)-Adrenoceptors do not contribute to phosphoinositide hydrolysis in adult
      rat cardiac myocytes.
AB  - We have used the alpha(1D)-adrenoceptor selective antagonist, BMY 7378, to
      investigate the presence of alpha(1D)-adrenoceptor subtype in adult rat heart by
      radioligand binding assays. We also determined the role of this subtype in
      stimulating phosphoinositide (PI) hydrolysis in adult rat cardiac myocytes. BMY
      7378 inhibited [(3)H]prazosin binding to cardiac membranes in a biphasic mode
      with a pK(i) of 9.19 +/- 0.26 for high affinity sites and 6.64 +/- 0.09 for low
      affinity sites. The inhibition of the adrenaline-induced stimulation of PI
      hydrolysis by BMY 7378 fitted a one-site model and the calculated pK(b) value
      (6.92 +/- 0.28) was consistent with the involvement of alpha(1A) and alpha(1B)
      adrenoceptors. In addition, BMY 7378, at concentrations up to 100 nM, did not
      significantly affect the concentration-response curves for the adrenaline-induced
      stimulation of PI hydrolysis. Taken together, these data suggest that alpha(1D)
      adrenoceptors are expressed in adult rat heart but this subtype is not involved
      in the adrenaline-induced stimulation of PI hydrolysis.

PMID- 11469803
TI  - Mechanism of monoterpene cyclization: stereochemical aspects of the
      transformation of noncyclizable substrate analogs by recombinant (-)-limonene
      synthase, (+)-bornyl diphosphate synthase, and (-)-pinene synthase.
AB  - The tightly coupled nature of the reaction sequence catalyzed by monoterpene
      synthases has prevented direct observation of the topologically required
      isomerization step leading from geranyl diphosphate to the presumptive, enzyme
      bound, tertiary allylic intermediate linalyl diphosphate, which ultimately
      cyclizes to the various monoterpene skeletons. Previous experimental approaches
      using the noncyclizable substrate analogs 6,7-dihydrogeranyl diphosphate and
      racemic methanogeranyl diphosphate, in attempts to dissect the cryptic
      isomerization step from the normally coupled reaction sequence, were thwarted by
      the limited product available from native monoterpene synthases and by the
      inability to resolve chiral monoterpene products at the microscale. These
      approaches were revisited using three recombinant monoterpene synthases and
      chiral phase capillary gas chromatographic methods to separate antipodal products
      of the substrate analogs. The recombinant monoterpene olefin synthases, (-)
      limonene synthase from spearmint and (-)-pinene synthase from grand fir, yielded
      essentially only achiral, olefin products (corresponding to the respective
      analogs and homologs of myrcene, trans-ocimene and cis-ocimene) from 6,7
      dihydrogeranyl diphosphate and (2S,3R)-methanogeranyl diphosphate; no significant
      amounts of terpenols or homoterpenols were formed, nor was direct evidence
      obtained for the formation of the anticipated analog and homolog of the tertiary
      intermediate linalyl diphosphate (i.e., 6,7-dihydrolinalyl diphosphate and
      homolinalyl diphosphate, respectively). In the case of recombinant (+)-bornyl
      diphosphate synthase from common sage, the achiral olefins were generated, as
      before, from 6,7-dihydrogeranyl diphosphate and (2R,3S)-methanogeranyl
      diphosphate, but 6,7-dihydrolinalool and homolinalool also comprised significant
      components of the respective product mixtures, indicating greater access of water
      to the active site of this enzyme compared to the olefin synthases; again, no
      direct evidence for the production of 6,7-dihydrolinalyl diphosphate or
      homolinalyl diphosphate was obtained. Resolution of the terpenol products of (+)
      bornyl diphosphate synthase, by chiral phase separation, revealed the predominant
      formation of (3R)-dihydrolinalool from dihydrogeranyl diphosphate and of (4S)
      homolinalool from (2R,3S)-methanogeranyl diphosphate. The opposite
      stereochemistries of these products indicates water trapping from opposite faces
      of the corresponding tertiary carbocationic intermediates of the respective
      reactions, a phenomenon that appears to result from the binding conformations of
      these substrate analogs. Although these experiments failed to provide direct
      evidence for the tertiary intermediate of the tightly coupled isomerization
      cyclization sequence, they did reveal a mechanistic difference between the olefin
      synthases and bornyl diphosphate synthase involving access of water as a
      participant in the reaction.

PMID- 11469804
TI  - Cyclic AMP-dependent protein kinase isoenzymes in human myeloid leukemia (HL60)
      and breast tumor (MCF-7) cells.
AB  - Combinations of retinoic acid (RA) and cAMP mediate many biological responses in
      a large variety of cell types. While the basis for the apparent synergistic
      effects of RA and cAMP are not clearly defined, it is likely that activation of
      PKA by cAMP is involved. However, literature reports concerning the identity of
      PKA isoforms in HL60 and MCF-7 cells are conflicting. The purpose of the present
      investigation is to identify PKA isoforms in HL60 and MCF-7 cells. Utilization of
      high-performance anion-exchange liquid chromatography, immunoblotting, and 8
      azido-cAMP photoaffinity binding resulted in the finding that HL60 cells contain
      PKA types I alpha and II alpha, while MCF-7 cells contain PKA types I alpha, II
      alpha, and II beta. PKA type I alpha in both HL60 and MCF-7 cells eluted from
      columns as two well-separated peaks. One peak eluted at a low salt concentration
      in agreement with previous reports. The second HL60 PKA type I alpha peak eluted
      at a salt concentration intermediate between that eluting the first peak and that
      eluting PKA type II alpha and contained approximately 62% of the total RI alpha
      protein. However, the second MCF-7 PKA type I alpha peak contained approximately
      66% of the total RI alpha protein and co-eluted with PKA types II alpha and II
      beta. This "contamination" of PKA type II fractions with PKA type I has led, in
      some cases, to interpretations that may need reevaluation.

PMID- 11469805
TI  - Chronic ethanol consumption and liver glycogen synthesis.
AB  - Chronic ethanol consumption results in a dramatic decrease in liver glycogen
      concentrations, which could be related to either a depressed rate of synthesis or
      an increased rate of breakdown. Earlier studies suggested that there is not an
      increase in the rate of glycogenolysis as glycogen phosphorylase activities are
      not elevated. In the present study it was observed that the incorporation of
      radiolabeled glucose into glycogen was significantly depressed in hepatocytes
      from ethanol-fed rats under both anaerobic and aerobic conditions. Chronic
      ethanol consumption decreased the total glycogen synthase (a + b) activity, which
      correlated closely with a loss in glycogen synthase protein. However, glycogen
      synthase messenger RNA levels were not depressed, which indicated
      posttranscriptional modifications affecting both activity and protein levels. The
      concentration of glucose transporter 1 was also decreased due to ethanol
      consumption, but glucose transporter 2 levels were not altered. This latter
      result suggests that glucose transport in the perivenous region of the liver
      lobule may be decreased in chronic ethanol consumers. The alterations in glucose
      transport protein and glycogen synthesis observed in this study may contribute to
      lowered glycogen synthesis, but do not appear to account for the magnitude of the
      decreases in glycogen levels and rate of synthesis. Indeed, ethanol effects on
      glycogen metabolism are likely to be exerted at several levels, including
      posttranslational modulation of enzyme activities.

PMID- 11469806
TI  - Mutations of the Walker B motif in the first nucleotide binding domain of
      multidrug resistance protein MRP1 prevent conformational maturation.
AB  - ATP-binding cassette (ABC) transporters couple the binding and hydrolysis of ATP
      to the translocation of solutes across biological membranes. The so-called
      "Walker motifs" in each of the nucleotide binding domains (NBDs) of these
      proteins contribute directly to the binding and the catalytic site for the MgATP
      substrate. Hence mutagenesis of residues in these motifs may interfere with
      function. This is the case with the MRP1 multidrug transporter. However,
      interpretation of the effect of mutation in the Walker B motif of NBD1
      (D792L/D793L) was confused by the fact that it prevented biosynthetic maturation
      of the protein. We have determined now that this latter effect is entirely due to
      the D792L substitution. This variant is unable to mature conformationally as
      evidenced by its remaining more sensitive to trypsin digestion in vitro than the
      mature wild-type protein. In vivo, the core-glycosylated form of that mutant is
      retained in the endoplasmic reticulum and degraded by the proteasome. A different
      substitution of the same residue (D792A) had a less severe effect enabling
      accumulation of approximately equal amounts of mature and immature MRP1 proteins
      in the membrane vesicles but still resulted in defective nucleotide interaction
      and organic anion transport, indicating that nucleotide hydrolysis at NBD1 is
      essential to MRP1 function.

PMID- 11469807
TI  - Cloning of Pichia pastoris Fet3: insights into the high affinity iron uptake
      system.
AB  - High-affinity iron uptake by yeast cells appears to require the presence of a
      complex formed on the plasma membrane by the multicopper oxidase Fet3 and the
      permease Ftr1 which work together to allow iron to enter safely inside the cell.
      The Pichia pastoris ferroxidase Fet3 has been cloned and it has been found to
      display high sequence similarity to other yeast multicopper oxidases, including
      all the predicted ligands for the catalytic copper atoms and for the iron
      substrate. P. pastoris appears to possess a high-affinity iron uptake system
      similar to that of S. cerevisiae, as far as regulation of expression is
      concerned. However, the P. pastoris high-affinity iron uptake system presents a
      K(m) value for iron almost ten times higher than that of S. cerevisiae, possibly
      to control iron fluxes over a wider range of concentrations of this metal, in
      order to avoid toxic iron overloading.

PMID- 11469808
TI  - Clinical measurement of steroid metabolism.
AB  - Analysis of steroids in biological samples is used routinely in the diagnosis of
      endocrine disorders. Binding assays (radioimmunoassays, immunosorbant
      immunoassays and non-radioactive immunoassays) are reported often for the
      analysis of single steroids in plasma and urine. Chromatographic methods (high
      performance liquid chromatography and gas chromatography) are used for steroid
      profiling where complex mixtures of steroids are analysed and the activity of
      biosynthetic and metabolic pathways deduced. Mass spectrometry is the ideal
      reference technique for detection of steroids, allowing high specificity and
      sensitivity. This review describes the practical issues concerning the quality of
      the assays performed and the potential pitfalls facing the analyst in the design
      of such methods. Novel approaches for the quantification of steroids, including
      microarrays and stable-isotope tracers are described, with these being applied in
      the research environment as opposed to routine biochemical laboratories.

PMID- 11469809
TI  - Congenital adrenal hyperplasias.
AB  - Congenital adrenal hyperplasia syndromes result from deficiencies of enzymes
      involved in corticosteroid biosynthesis. Most commonly, they are due to mutations
      in 21-hydroxylase. This chapter describes the clinical diagnosis and management
      of congenital adrenal hyperplasias throughout life, including in the fetus, child
      and adult. These clinical recommendations are explained in the context of the
      molecular and biochemical characteristics of the diseases.

PMID- 11469810
TI  - Disorders of mineralocorticoid synthesis.
AB  - Abnormalities of mineralocorticoid synthesis and/or metabolism profoundly affect
      the regulation of electrolyte and water balance and of blood pressure.
      Characteristic changes in extracellular potassium, sodium and hydrogen ion
      concentrations are usually diagnostic. Serious deficiency may be acquired, for
      example in Addison's disease, or inherited. In most of the inherited syndromes,
      the precise molecular changes in specific steroidogenic enzymes have been
      identified. Mineralocorticoid excess may be caused by aldosterone or 11
      deoxycorticosterone by inadequate conversion of cortisol to cortisone by 11beta
      hydroxysteroid dehydrogenase type 2 in target tissues (see Chapter 4), by
      glucocorticoid receptor deficiency or by constitutive activation of renal sodium
      channels. Changes in electrolyte balance and renin as well as the abnormal
      pattern of corticosteroid metabolism are usually diagnostic. Where these
      abnormalities are inherited (e.g. 11beta- or l7alpha-hydroxylase deficiencies,
      glucocorticoid remediable hyperaldosteronism (GRA), receptor defects, Liddle's
      syndrome), the molecular basis is again usually known and, in some cases, may
      provide the simplest diagnostic tests. Primary aldosteronism, although readily
      identifiable, presents problems of differential diagnosis, important because
      optimal treatment is different for each variant. Moreover, the mechanisms by
      which the variants develop are poorly understood. Finally, a significant
      proportion of patients with essential hypertension show characteristics of mild
      mineralocorticoid excess, for example low renin levels. Is this relevant to
      pathophysiology and, if so, is the effect induced via classic mechanisms of
      action or through newly discovered direct actions on the brain, heart and blood
      vessels? These questions are the subject of current research.

PMID- 11469811
TI  - Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase.
AB  - Two isoforms of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD)
      interconvert the active glucocorticoid, cortisol, and inactive cortisone. 11beta
      HSD1 is believed to act in vivo predominantly as an oxo-reductase using NADP(H)
      as a cofactor to generate cortisol. In contrast, 11beta-HSD2 acts exclusively as
      an NAD-dependent dehydrogenase inactivating cortisol to cortisone, thereby
      protecting the mineralocorticoid receptor from occupation by cortisol. In
      peripheral tissues, both enzymes serve to control the availability of cortisol to
      bind to the corticosteroid receptors. Defective expression of 11beta-HSD2 is
      implicated in patients with hypertension and intra-uterine growth retardation,
      while 11beta-HSD1 appears to be intricately involved in the conditions of
      apparent cortisone reductase deficiency, insulin resistance and visceral obesity.
      The ability of peripheral tissues to regulate corticosteroid concentrations
      through 11beta-HSD isozymes is established as an important mechanism in the
      pathogenesis of diverse human diseases. Modulation of enzyme activity may offer a
      novel therapeutic approach to treating human disease while circumventing the
      consequences of systemic glucocorticoid excess or deficiency.

PMID- 11469812
TI  - Steroid 5alpha-reductases and 3alpha-hydroxysteroid dehydrogenases: key enzymes
      in androgen metabolism.
AB  - Androgen action in mammals can be regulated at the pre-receptor level by the
      intracellular formation and degradation of potent androgens, such as 5alpha
      dihydrotestosterone (5alpha-DHT). In androgen target tissues (e.g. prostate),
      5alpha-DHT is formed from circulating testosterone by the action of the type 2
      steroid 5alpha-reductase (5alpha-R) and its action is terminated by the action of
      a reductive 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) which forms the weak
      androgen 3alpha-androstanediol. Oxidative 3alpha-HSD isoforms, however, can
      provide an alternative source of potent androgens by converting 3alpha
      androstanediol to 5alpha-DHT. Working in concert, 5alpha-Rs and 3alpha-HSDs
      determine the amount and the type of androgen available for the androgen receptor
      and hence affect transcription of genes under androgen control. In peripheral
      tissues (e.g. liver), type 1 5alpha-R and reductive 3alpha-HSD isoforms work
      consecutively to eliminate androgens and protect against hormone excess. Thus,
      different 5alpha-R and 3alpha-HSD isoforms participate in distinct anabolic and
      catabolic processes and their important roles in androgen action render them drug
      targets for the treatment of androgen-dependent diseases.

PMID- 11469813
TI  - Genetics of vitamin D biosynthesis and its disorders.
AB  - The principal hormone regulator of bone mineralization is vitamin D, which must
      be activated by a metabolic pathway consisting of a 25-hydroxylase and a 1alpha
      hydroxylase to yield 1,25 (OH)(2)D. The hormonal regulation of vitamin D
      activation is at the level of the 1alpha-hydroxylase. We review the biology of
      vitamin D, the biochemistry of its activation and the molecular biology of the
      vitamin D-metabolizing enzymes. Recent advances have resulted in the cloning of
      the human vitamin D 1alpha-hydroxylase and the identification of mutations in its
      gene that cause Vitamin D Dependent Rickets type I.

PMID- 11469814
TI  - Steroid metabolism in metabolic syndrome X.
AB  - Preceding chapters in this volume describe relatively rare conditions associated
      with qualitative rather than quantitative changes in enzymes involved in steroid
      synthesis and metabolism. In this chapter, several examples show how more subtle
      variations in activities of the same enzymes may be important in the
      pathophysiology of common diseases of complex aetiology. This chapter reviews
      evidence for deranged steroid metabolism in patients with the 'insulin resistance
      syndrome'. In summary, patients with essential hypertension may have subtle
      11beta-hydroxylase or 11beta-hydroxysteroid dehydrogenase type 2 deficiency
      resulting in mild mineralocorticoid excess. Patients with obesity, and/or
      associated hirsutism or hyperglycaemia, have evidence of altered peripheral
      metabolism of androgens (increased 5alpha-reductase) and glucocorticoids (altered
      11beta-hydroxysteroid dehydrogenase type 1, resulting in enhanced cortisol levels
      in adipose tissue). Some of these changes in steroid metabolism lend themselves
      to therapeutic manipulation which may provide novel strategies to reduce
      cardiovascular risk.

PMID- 11469817
TI  - Introduction to, and classification of, the systemic vasculitides.
AB  - This overview serves as an introduction to the systemic vasculitides, which are a
      group of heterogeneous disorders sharing a common pathophysiological mechanism
      leading to blood vessel inflammation and tissue necrosis. Our lack of
      understanding of the aetiology for most forms of vasculitis has resulted in the
      development of a classification system, which is primarily based on vessel size.
      Such a system assists in the grouping together of similar conditions for the
      purposes of multi-centre studies. Difficulties arise in classification of the
      vasculitides due to considerable overlap of clinico-pathological features; for
      example, microscopic polyangiitis (MPA), Wegener's granulomatosis (WG) and Churg
      Strauss syndrome (CSS) may all cause the identical renal lesion of necrotizing
      glomerulonephritis. The rationale for treatment often depends on the type of
      vasculitis and on the extent of organ involvement. Treatment may be similar for
      different types of disease. The lack of validated diagnostic criteria has,
      however, resulted in the application of classification criteria in their place,
      and has highlighted the limited usefulness of classification criteria in clinical
      practice. Classification systems should assist in the determination of therapy
      and prediction of outcomes, but have many limitations, which are discussed
      further in this review.

PMID- 11469818
TI  - Diagnosis of vasculitis.
AB  - Vasculitis is a process that results from the inflammation of blood vessels and
      can occur de novo or secondary to a variety of diseases or drugs. Clinical
      presentation depends on the size and distribution of vessels involved. Anti
      neutrophil cytoplasmic antibodies (ANCA) have been shown to have variable
      sensitivity in making the diagnosis of specific vasculitic syndromes, therefore
      histological confirmation may be necessary. Angiography is a useful tool in
      evaluating disease of large and medium-sized vessels that are inaccessible or
      potentially dangerous to biopsy. New imaging modalities are becoming more useful
      in diagnosing vessel wall changes, particularly in large-vessel vasculitides. In
      clinical practice it is not always possible to classify or apply a specific label
      to a patient with vasculitis, but for appropriate patient management it is
      important to define the extent and severity of disease and to exclude underlying
      secondary causes.

PMID- 11469819
TI  - Activity, damage and outcome in systemic vasculitis.
AB  - Current therapy has transformed the prognosis of the systemic vasculitides from
      diseases that had a high acute mortality rate to chronic relapsing diseases with
      high rates of morbidity. This improved survival has highlighted the need for
      better methods of monitoring disease activity and recording the accumulation of
      organ damage that occurs during the course of the disease. Several clinical
      indices have been developed that record disease activity, damage and the extent
      of disease. These validated indices allow a detailed assessment of the patient's
      response to therapy and provide an essential tool for insuring uniformity of
      patient monitoring in multi-centre trials. In addition, more data are now
      available supporting the use of these assessment tools as prognostic and outcome
      criteria for clinical studies. The development, properties, application and inter
      relationships of the available clinical assessment tools for patients with
      systemic vasculitis are reviewed in this chapter.

PMID- 11469820
TI  - Pathogenesis: immunogenetic factors.
AB  - The occurrence, albeit infrequent, of systemic vasculitis in closely related
      family members suggests that both environmental and genetic factors may play a
      role in the pathogenesis of these diseases. Malfunction of immune regulation in
      the systemic vasculitides may indicate a role for genes that encode molecules
      critical to the immune responses. The extremely polymorphic sequences of MHC
      molecules may provide a structural basis for associations of MHC genes and
      systemic vasculitis. This review summarizes recent reports of MHC associations,
      mechanisms by which MHC may play a role in certain vasculitides, and also
      examines the role for genes encoding non-MHC molecules, such as Fcgamma
      receptors, cytokines and T cell co-stimulators. Data suggest that the
      pathogenesis of systemic vasculitides such as giant-cell arteritis, Takayasu's
      arteritis and Wegener's granulomatosis might be governed by multiple genes
      encoding host defence molecules, in conjunction with environmental factors.

PMID- 11469821
TI  - Tissue targeting and disease patterns in systemic vasculitis.
AB  - The systemic vasculitides include a group of diseases with highly heterogeneous
      organ distribution and disease expression patterns. The mechanisms mediating
      tissue targeting in systemic vasculitis are largely unknown. Mechanical forces
      may contribute to the distribution of lesions in immune complex-mediated
      vasculitis. The site at which the antigen is encountered may be crucial in
      determining the location of inflammatory infiltrates in some vasculitides. Co
      existence of different immunopathogenic mechanisms with variable dominance may
      generate diversity in disease presentation patterns. Heterogeneous and
      incompletely understood triggering mechanisms attract inflammatory cells to the
      site of interest through sophisticated molecular mechanisms: interplay between
      leukocyte receptors and endothelial ligands, and interactions between chemokines
      and chemokine receptors. Even with a similar distribution of lesions, patients
      with vasculitis may display highly variable clinical manifestations. Variations
      in genes involved in immune response might determine the severity of disease, the
      intensity of the systemic inflammatory response, the degree of vessel occlusion
      and the response to therapy.

PMID- 11469822
TI  - Management of systemic vasculitis.
AB  - The systemic vasculitides are a wide-ranging group of diseases that are
      characterized by the presence of blood vessel inflammation. Despite this common
      feature, each type of vasculitis has a unique variety of clinical manifestations
      that influences its degree of disease severity and ultimately its management.
      Immunosuppressive therapy forms the foundation of treatment for almost all forms
      of systemic vasculitis. Because of this, treatment can be associated with its own
      risk of morbidity, or even mortality, related to specific medication side-effects
      or infections which occur as a result of impaired host defences. This chapter
      seeks to review the approach to management in selected forms of systemic
      vasculitis. Questions examined include the following. When should one treat
      systemic vasculitis? How does the nature of the disease and its severity affect
      treatment decisions? What are the data regarding the effectiveness of individual
      therapeutic regimens?

PMID- 11469823
TI  - New therapeutic aspects: haemopoietic stem cell transplantation.
AB  - Primary systemic vasculitis responds well to intensive immunosuppression,
      particularly with cyclophosphomide. Use of the latter is restricted by side
      effects, particularly in relapsing disease. Techniques which allow more complete
      immunosuppression have an obvious attraction in autoimmune disease. They are
      particularly suitable for vasculitis which can go into long-lasting remission
      even with standard therapy in many cases. The conditioning used for stem cell
      transplantation allows more complete deletion of auto aggressive T-cell clones,
      with subsequently haemopoietic rescue by previously harvested stem cell
      precursors. The procedure also has immune potentiating effects, perhaps by
      promoting peripheral suppressor mechanisms. These may be important even though
      immune ablation is not achieved. With rigorous patient selection, experience with
      this technique in vasculitis may be broadened.

PMID- 11469824
TI  - New approaches to treatment in systemic vasculitis: biological therapies.
AB  - Although the effectiveness of biological agents in systemic vasculitis is
      unproven, their introduction heralds a new era of vasculitis treatment. These
      agents offer the promise of targeted immunotherapies; the possibility of greater
      efficacy (and fewer side-effects) than conventional vasculitis treatments; and
      the potential to provide novel insights into the pathophysiology of these
      diseases-insights that may be gained only by using these agents in humans.
      Challenges to the investigation of these therapies in the systemic vasculitides
      exist, but important basic and clinical investigations are already in progress.
      We review the major issues facing the investigation of biological agents in
      vasculitis; examine the rationale for believing that biological strategies in
      vasculitis will be efficacious; identify several candidate targets for biological
      approaches; and discuss the results to date of early studies. The potential
      biological targets discussed include cytokines such as tumour necrosis factor;
      interleukins-1, -6, and -12; interferon-gamma; the co-stimulatory molecules B7-1
      and B7-2; and others.

PMID- 11469828
TI  - Invited review article: surgery for Volkmann's ischaemic contracture.

PMID- 11469829
TI  - A biomechanical analysis of the modified Tsuge suture technique for repair of
      flexor tendon lacerations.
AB  - Thirty-six flexor tendons from fresh frozen cadavers were randomized to three
      types of repairs: a Kessler-Tajima, a 4-strand modified Tsuge, and a 6-strand
      modified Tsuge. All repairs were accompanied by a standard epitendinous suture.
      The repaired tendons were then tested to initial gap and ultimate failure in an
      Instron machine. The average forces to ultimate failure were 31.8 N (SD, 8.8),
      48.4 N (SD, 10.7), and 64.2 N (SD, 11.0) respectively. The 6-strand modified
      Tsuge suture was significantly stronger than the other repairs and the 4-strand
      modified Tsuge was significantly stronger than the 2-strand Kessler-Tajima. The 6
      strand and 4-strand modified Tsuge repairs appear strong enough to withstand the
      forces generated during early active range of motion flexor tendon rehabilitation
      protocols. Clinical trials are required to evaluate the usefulness of these
      repairs.

PMID- 11469830
TI  - Comparison of postoperative early active mobilization and immobilization in vivo
      utilising a four-strand flexor tendon repair.
AB  - We evaluated a technique of four-strand double-modified locking Kessler flexor
      tendon repair in healing tendons. Seventy-two canine flexor digitorum profundus
      tendons in Zone 2 were repaired and evaluated following either active
      mobilization or immobilization at 0, 7, 14, 28 and 42 days after surgery. Fifty
      six tendons were examined for gap and ultimate strength using a tensile testing
      machine and 16 were evaluated with standard hematoxylin and eosin, and Masson's
      trichrome staining. All tendons healed without rupture or gap formation of more
      than 1 mm, thus demonstrating that this repair technique has enough tensile
      strength to withstand early active mobilization. The gap and ultimate strength of
      actively mobilized tendons did not decrease significantly during the first 7
      days, and were significantly greater than those of immobilized tendons throughout
      the 42-day study period. Actively mobilized tendons healed without the extrinsic
      adhesions and large tendon calluses that were found in immobilized tendons.

PMID- 11469831
TI  - An in vitro comparison of human flexor and extensor tendon cells.
AB  - This study examined the in vitro phenotype of cells cultured from both flexor and
      extensor tendons. Matrix proteins secreted by tendon cells were examined,
      together with their response to mechanical strain, using cells from the two types
      of tendon. Immunocytochemical staining using specific antibodies to matrix
      proteins demonstrated that flexor tendon cells synthesised only three of the five
      proteins stained for, whilst extensor tendon cells synthesised all five. Gel
      electrophoresis (used to separate mixtures of proteins) demonstrated that protein
      secretion was similar for both cell types. Both cell types showed similar
      patterns of synthesis for total collagen and total protein over time. No
      difference was found in the response to cyclical strain of cells from the two
      types of tendon; both cell proliferation and collagen synthesis were stimulated.
      The study demonstrated that cells obtained from two different types of tendon
      behave similarly when exposed to identical environmental conditions in vitro.

PMID- 11469832
TI  - Free vascularized toe joint transfer to the hand. A technique for simultaneous
      reconstruction of the soft tissue.
AB  - Twelve patients underwent reconstruction of injured finger joints using our
      technique of a vascularized transfer of the second toe proximal interphalangeal
      joint. The age of the patients at operation ranged from 7 to 47 years and the
      postoperative follow-up was 9 to 48 months. All the joint transfers survived and
      united with resolution of the preoperative joint pain, deformity and instability.
      The average range of motion of the reconstructed joints was 59 degrees in the
      proximal interphalangeal and 54 degrees in the metacarpophalangeal joints. No
      patient complained of pain or functional deficits in the donor foot.

PMID- 11469833
TI  - Definition of union after acute fracture and surgery for fracture nonunion of the
      scaphoid.

PMID- 11469834
TI  - MRI assessment of the proximal pole of the scaphoid after internal fixation with
      a titanium alloy Herbert screw.
AB  - We report a series of scaphoid fractures fixed with titanium alloy Herbert screws
      in which postoperative Magnetic Resonance Imaging (MRI) was used to assess the
      marrow signal in the proximal pole of the scaphoid and thus detect the presence
      of avascular necrosis. The artefact produced by the titanium alloy Herbert screw
      did not preclude this assessment.

PMID- 11469835
TI  - Longstanding nonunions of scaphoid fractures with bone loss: successful
      reconstruction with vascularized bone grafts.
AB  - Vascularized bone graft from the dorsum of distal radius was used to treat 22
      nonunions of scaphoid fractures, with a mean delay of 4 years from the initial
      injury. Four of the eight patients with associated scapho-styloid arthritis also
      underwent a closing wedge osteotomy of the distal radius. Follow-up time ranged
      from 14 to 74 months. Union was accomplished in 6 to 12 weeks and wrist range of
      motion and grip strength improved postoperatively in all patients. Complete
      absence of pain was noted in 16 patients and the other six, all of whom had
      arthritic wrist changes or carpal collapse, only experienced pain with strenuous
      activities. The simple graft dissection, the avoidance of anastomoses and the
      lack of donor site morbidity are additional advantages to this surgical
      technique, which is successful even in cases with an avascular proximal pole.

PMID- 11469836
TI  - Preservation of denervated muscle form and function by clenbuterol in a rat model
      of peripheral nerve injury.
AB  - The effects of clenbuterol in preserving the form and function of muscle after
      unilateral sciatic nerve division and epineural repair were investigated in a rat
      model. The drug (a beta2-adrenoceptor agonist) was administered daily for six
      weeks by gastric gavage (10 microg/kg body weight), interrupted every 5 days by a
      2 day omission of dosing to avoid drug desensitization. Clenbuterol reduced the
      loss of wet weight, total protein, muscle fibre cross sectional area and (in
      part) contractile forces in denervated hindlimb muscles, with most effects
      lasting until reinnervation. The effects were dependent on muscle type, with slow
      twitch oxidative muscle (soleus) and mixed-fibre (gastrocnemius) showing greater
      sensitivity to the drug than fast-twitch muscle (extensor digitorum longus).
      Anabolic effects on the contralateral innervated muscles tended to be small. The
      results suggest a potential for the adjuvant use of selective beta -adrenoceptor
      agonists in the management of peripheral nerve injuries in humans.

PMID- 11469837
TI  - Nerve regeneration enhancement by tourniquet.
AB  - The use of tourniquet compression as a non-invasive method to enhance axonal
      regeneration was assessed in the rat sciatic nerve. One hind limb of the rat was
      subjected to compression by a tourniquet set at 300 mmHg for 30 or 120 min
      followed by bilateral test crush lesions performed either directly or after a
      conditioning interval of 3 or 6 days, with the non-compressed side serving as a
      control. Axonal regeneration distances were evaluated after 3 days by the pinch
      reflex test. We found that compression caused an increased outgrowth length of
      sensory axons compared to the controls. The effect was most obvious after 120 min
      of compression with a conditioning interval of 6 days. Tourniquet compression has
      a conditioning lesion effect on peripheral nerve and may enhance nerve
      regeneration.

PMID- 11469838
TI  - A modified technique of four-bone fusion for advanced carpal collapse (SLAC/SNAC
      wrist).
AB  - This study reports the outcome of 16 patients treated with a modified four-bone
      fusion for symptomatic stage II and III advanced carpal collapse. The technique
      is based on fusion of the capitate, lunate, hamate and triquetrum using an
      autogenous corticocancellous bone-graft fixed with screws. The void left behind
      after scaphoid excision was filled with an extensor carpi radialis longus
      anchovy. After an average follow up of 3 years; there were 13 excellent and three
      good outcomes. In every patient pain relief was achieved with preservation of
      joint motion and grip strength. All the patients were able to return to their
      previous activities and jobs. Radiographic evaluation showed bone fusion in all
      16 patients with a slight decrease in carpal height but a well preserved
      radiolunate joint space. In conclusion, this technique provides immediate stable
      fixation and early mobilization and assures bone fusion.

PMID- 11469839
TI  - Wrist arthrodesis with the AO titanium wrist fusion plate: a consecutive series
      of 42 cases.
AB  - In a 4 year period (1996-1999), 42 total wrist fusions in 25 men and 17 women
      were performed using the AO/ASIF Titanium wrist fusion plate. The median age of
      the patients at the time of surgery was 41 (range, 19-72) years. The indication
      for fusion was post-traumatic arthritis in 29 wrists, Kienbock's disease in
      eight, rheumatoid arthritis in three, mono-arthritis in one and Volkmann's
      contracture in one. All patients were reviewed at a median follow-up of 23
      (range, 6-50) months. The Buck-Gramcko and Lohmann score for functional
      evaluation was excellent in 35, good in 5 and satisfactory in 2 patients. We
      conclude that wrist arthrodesis with the AO/ASIF Titanium wrist fusion plate is
      an excellent option for treatment of various painful disorders of the wrist.

PMID- 11469840
TI  - Palmar segmental aponeurectomy for Dupuytren's disease with metacarpophalangeal
      flexion contracture.
AB  - Eighty palmar segmental aponeurectomies were performed between 1993 and 1999 for
      well-localized palmar cords with metacarpophalangeal flexion contracture. A
      retrospective patient review with a minimum follow-up of 1-year demonstrated a 6%
      rate of recurrent metacarpophalangeal flexion and two minor complications.
      Segmental aponeurectomy rather than limited fasciectomy is recommended for this
      type of disease.

PMID- 11469841
TI  - Langerhans cells in Dupuytren's contracture.
AB  - We have examined biopsies of Dupuytren's contracture palmar fascia, overlying
      subcutis and skin, and have correlated the distribution of gross macroscopic
      changes in the hand, mapped pre- and intraoperatively, with light microscopic
      immunohistochemical findings. We report increased numbers of S100 positive
      Langerhans cells (an epidermal cell of dendritic lineage) and CD45 positive
      cells, both in "nodules" and at dermo-epidermal junctions, in the biopsied
      tissues. This suggests that Langerhans cells migrate from the epidermis into
      Dupuytren's contracture tissue, possibly in response to local changes in levels
      of inflammatory cytokines within the tissue. Our findings, together with other
      reports of increased numbers of dermal dendrocytes and inflammatory cells in
      Dupuytren's contracture tissue, lend circumstantial support to the "extrinsic
      theory" of the pathogenesis of Dupuytren's contracture. However, the earliest
      stages of the disease process have not been defined, and therefore the events
      which ultimately produce fibrosis in the palmar fascial complex in susceptible
      individuals could begin in the skin and/or within deeper tissues, especially
      where there is dysregulation of the immune system.

PMID- 11469842
TI  - Lipofibromatous hamartoma of the median nerve and its associated conditions.
AB  - This study reports on ten cases of lipofibromatous hamartoma of the median nerve,
      with specific references to its associated conditions. Macrodactyly was the most
      common associated condition and was seen in 6 cases. Two cases had associated
      fatty tumours and another two had bony tumours. The literature was reviewed and a
      classification of the sites of involvement of the median nerve and its associated
      conditions is suggested.

PMID- 11469843
TI  - Flexor tendon anomalies in a patient with carpal tunnel syndrome.
AB  - A case of an anomalous interconnection between the tendons of the flexor pollicis
      longus and the flexor digitorum profundi to both the index and middle fingers at
      the wrist of a patient presenting with carpal tunnel syndrome is described. The
      contents of the carpal tunnel should be inspected carefully at the time of median
      nerve decompression in cases where preoperative clinical examination suggests
      associated pathologies.

PMID- 11469844
TI  - Preoperative ampiroxicam reduces postoperative pain after hand surgery.
AB  - We performed a double blind randomised controlled study to assess whether the
      preoperative administration of ampiroxicam reduced the level of postoperative
      pain in 120 patients who underwent surgery to a hand under brachial plexus block.
      We found that preoperative (pre-emptive) administration of ampiroxicam
      significantly reduced the postoperative pain levels and the need for
      postoperative analgesia.

PMID- 11469845
TI  - Localized amyloid deposition in trigger finger.
AB  - Trigger finger is due to degeneration and thickening of the proximal portion (A1
      pulley) of the flexor tendon sheath, which causes constriction of the flexor
      tendon. This study reports the presence of localized amyloid deposition in the
      tendon sheath of 11 of 47 cases (23%) of idiopathic primary trigger finger.
      Amyloid deposits were only found in patients aged over 46 years old and were
      present around cells and at sites of mucinous and fibrinoid degeneration which
      contained highly sulphated glycosaminoglycans. The pathogenic significance of
      these deposits is uncertain but their small size and presence only in middle-aged
      and elderly adults suggests that they represent a form of age-associated amyloid
      deposition.

PMID- 11469846
TI  - Temporary ischaemia of the scaphoid in a child.
AB  - We describe a case of a 12-year-old boy who developed acute ischaemia of the
      entire scaphoid following simple trauma to the wrist. No fracture was evident;
      however, MRI and bone scintigraphy at the time of the injury revealed complete
      ischaemia of the scaphoid. A repeat MRI at 6 months showed evidence of incomplete
      revascularisation of the scaphoid.

PMID- 11469847
TI  - Locking of the proximal interphalangeal joint of the little finger.
AB  - Locking of the metacarpophalangeal joints is well documented, but locking of
      other joints in the finger has not been described. We present a case of locking
      of the little finger proximal interphalangeal joint due to an osteophyte
      impinging on the extensor tendon.

PMID- 11469848
TI  - A comparison study of trapezial excision alone versus trapezial excision with
      ligament reconstruction and tendon interposition.

PMID- 11469850
TI  - The use of silicone tubing in the late repair of the median and ulnar nerves in
      the forearm.

PMID- 11469851
TI  - Re: Should methotrexate be stopped before surgery in patients with rheumatoid
      arthritis.

PMID- 11469853
TI  - Domain shuffling as a tool for investigation of protein function: substitution of
      the cysteine-rich region of Raf kinase and PKC eta for that of yeast Pkc1p.
AB  - With the completion of the sequences of entire genomes, the need for functional
      characterisation of proteins and their domains is becoming acute. Conserved
      regions within proteins often share overlapping functions but despite this
      conservation may fulfil quite different tasks in different species. In this work,
      we investigated the cysteine-rich motif (C1 domain) of yeast protein kinase C
      (Pkc1p) as a model to establish a test system for domain function. C1 domains
      activate kinases through binding of either diacylglycerol and/or
      phosphatidylserine, as in many members of the protein kinase C (PKC) family, or
      by binding small GTPases, as in Raf kinase. In contrast to other members of the
      protein kinase C superfamily, Pkc1p of Saccharomyces cerevisiae is activated via
      binding of the small G-protein Rho1p to its C1 domain. We developed a system for
      domain shuffling to establish the function of C1 domains from human Raf kinase
      and rat PKC eta in yeast. Only the C1 domain from Raf kinase enabled the chimeric
      enzyme to bind Rho1p when substituted for the native yeast domain. Accordingly, a
      chimeric Pkc1p carrying the C1 from Raf kinase, but not that from PKC eta, was
      able to partially complement the phenotypes of a yeast pkc1 deletion mutant. We
      interpret these data as further evidence that interaction with a small GTPase is
      the main regulatory function of the C1 domain in yeast.

PMID- 11469854
TI  - Crystal structure of a cocaine-binding antibody.
AB  - Murine monoclonal antibody GNC92H2 was elicited by active immunization with a
      cocaine immunoconjugate and binds free cocaine with excellent specificity and
      moderate affinity. Improvement of affinity, as well as humanization of GNC92H2,
      would be advantageous in immunopharmacotherapy for cocaine addiction, and for
      emergency cases of drug overdose. Toward this end, the crystal structure of an
      engineered murine-human chimeric Fab of GNC92H2 complexed with cocaine was
      determined at 2.3 A resolution. Structural analysis reveals a binding pocket with
      high shape and charge complementarity to the cocaine framework, which explains
      the specificity for cocaine, as opposed to the pharmacologically inactive cocaine
      metabolites. Importantly, the structure provides a foundation for mutagenesis to
      enhance the binding affinity for cocaine and potent cocaine derivatives, such as
      cocaethylene, and for additional humanization of the antibody.

PMID- 11469855
TI  - Large-scale analysis of the Alu Ya5 and Yb8 subfamilies and their contribution to
      human genomic diversity.
AB  - We have utilized computational biology to screen GenBank for the presence of
      recently integrated Ya5 and Yb8 Alu family members. Our analysis identified 2640
      Ya5 Alu family members and 1852 Yb8 Alu family members from the draft sequence of
      the human genome. We selected a set of 475 of these elements for detailed
      analyses. Analysis of the DNA sequences from the individual Alu elements revealed
      a low level of random mutations within both subfamilies consistent with the
      recent origin of these elements within the human genome. Polymerase chain
      reaction assays were used to determine the phylogenetic distribution and human
      genomic variation associated with each Alu repeat. Over 99 % of the Ya5 and Yb8
      Alu family members were restricted to the human genome and absent from
      orthologous positions within the genomes of several non-human primates,
      confirming the recent origin of these Alu subfamilies in the human genome.
      Approximately 1 % of the analyzed Ya5 and Yb8 Alu family members had integrated
      into previously undefined repeated regions of the human genome. Analysis of
      mosaic Yb8 elements suggests gene conversion played an important role in
      generating sequence diversity among these elements. Of the 475 evaluated
      elements, a total of 106 of the Ya5 and Yb8 Alu family members were polymorphic
      for insertion presence/absence within the genomes of a diverse array of human
      populations. The newly identified Alu insertion polymorphisms will be useful
      tools for the study of human genomic diversity.

PMID- 11469856
TI  - Identification of nucleophosmin/B23, an acidic nucleolar protein, as a
      stimulatory factor for in vitro replication of adenovirus DNA complexed with
      viral basic core proteins.
AB  - The processes governing chromatin remodeling and assembly, which occur prior to
      and/or after transcription and replication, are not completely understood. To
      understand the mechanisms of transcription and replication from chromatin
      templates, we have established in vitro replication and transcription systems
      using adenovirus (Ad) DNA complexed with viral basic core proteins, called Ad
      core, as a template. Using this system, we have previously identified, from HeLa
      cells, template activating factor-I as a stimulatory factor for the Ad core DNA
      replication. Here, using this system as a tool, we identified and purified a
      novel template activating factor activity that consists of two acidic
      polypeptides whose apparent molecular masses are 38 kDa and 37 kDa. These two
      polypeptides correspond to two splicing variants of nucleolar phosphoprotein,
      nucleophosmin/B23. Recombinant B23 proteins stimulate the Ad core DNA
      replication, and the acidic regions of B23 proteins are important for its
      activity. In addition, B23 proteins directly bind to core histones and transfer
      them to naked DNA. Furthermore, chromatin components such as histones and
      topoisomerase II are co-immunoprecipitated with B23 from cell extracts. These
      observations lead to a hypothesis that nucleophosmin/B23 is involved in
      structural changes of chromatin, thereby regulating transcription and replication
      within the ribosomal DNA region or maintaining the nucleolar structure.

PMID- 11469857
TI  - Identification of 66 box C/D snoRNAs in Arabidopsis thaliana: extensive gene
      duplications generated multiple isoforms predicting new ribosomal RNA 2'-O
      methylation sites.
AB  - Dozens of box C/D small nucleolar RNAs (snoRNAs) have recently been found in
      eukaryotes (vertebrates, yeast), ancient eukaryotes (trypanosomes) and archae,
      that specifically target ribosomal RNA sites for 2'-O-ribose methylation.
      Although early biochemical data revealed that plant rRNAs are among the most
      highly ribomethylated in eukaryotes, only a handful of methylation guide snoRNAs
      have been characterized in this kingdom. We report 66 novel box C/D snoRNAs
      identified by computational screening of Arabidopsis genomic sequences that are
      expressed in vivo from either single genes, 17 different clusters or three
      introns. At the structural level, many box C/D snoRNAs have dual antisense
      elements often matching rRNA regions close to each other on the rRNA secondary
      structure, which is reminiscent of their archaeal counterparts. Remarkable
      specimens are found that display two antisense elements having the potential to
      form an extended snoRNA-rRNA duplex of 23 to 30 nt, in line with the hypothetical
      function of box C/D snoRNAs in pre-rRNA folding or chaperoning. In contrast to
      other species, many Arabidopsis snoRNAs are found in multiple isoforms mainly
      resulting from two different mechanisms: large chromosomal duplications and small
      tandem duplications producing polycistronic genes. The discovery of numerous
      different snoRNAs, some of them arising from common ancestors, provide new
      insights to understand snoRNAs evolution and the birth of new rRNA methylation
      sites in plants and other organisms.

PMID- 11469858
TI  - Structure-based analysis of protein-RNA interactions using the program ENTANGLE.
AB  - Until recently, drawing general conclusions about RNA recognition by proteins has
      been hindered by the paucity of high-resolution structures. We have analyzed 45
      PDB entries of protein-RNA complexes to explore the underlying chemical
      principles governing both specific and non-sequence specific binding. To
      facilitate the analysis, we have constructed a database of interactions using
      ENTANGLE, a JAVA-based program that uses available structural models in their PDB
      format and searches for appropriate hydrogen bonding, stacking, electrostatic,
      hydrophobic and van der Waals interactions. The resulting database of
      interactions reveals correlations that suggest the basis for the discrimination
      of RNA from DNA and for base-specific recognition. The data illustrate both major
      and minor interaction strategies employed by families of proteins such as tRNA
      synthetases, ribosomal proteins, or RNA recognition motifs with their RNA
      targets. Perhaps most surprisingly, specific RNA recognition appears to be
      mediated largely by interactions of amide and carbonyl groups in the protein
      backbone with the edge of the RNA base. In cases where a base accepts a proton,
      the dominant amino acid donor is arginine, whereas in cases where the base
      donates a proton, the predominant acceptor is the backbone carbonyl group, not a
      side-chain group. This is in marked contrast to DNA-protein interactions, which
      are governed predominantly by amino acid side-chain interactions with functional
      groups that are presented in the accessible major groove. RNA recognition often
      proceeds through loops, bulges, kinks and other irregular structures that permit
      use of all the RNA functional groups and this is seen throughout the protein-RNA
      interaction database.

PMID- 11469859
TI  - X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP
      at 1.95 A resolution.
AB  - The X-ray structure of Mycobacterium tuberculosis TMP kinase at 1.95 A resolution
      is described as a binary complex with its natural substrate TMP. Its main
      features involve: (i) a clear magnesium-binding site; (ii) an alpha-helical
      conformation for the so-called LID region; and (iii) a high density of positive
      charges in the active site. There is a network of interactions involving highly
      conserved side-chains of the protein, the magnesium ion, a sulphate ion mimicking
      the beta phosphate group of ATP and the TMP molecule itself. All these
      interactions conspire in stabilizing what appears to be the closed form of the
      enzyme. A complete multialignment of all (32) known sequences of TMP kinases is
      presented. Subtle differences in the TMP binding site were noted, as compared to
      the Escherichia coli, yeast and human enzyme structures, which have been reported
      recently. These differences could be used to design specific inhibitors of this
      essential enzyme of nucleotide metabolism. Two cases of compensatory mutations
      were detected in the TMP binding site of eukaryotic and prokaryotic enzymes. In
      addition, an intriguing high value of the electric field is reported in the
      vicinity of the phosphate group of TMP and the putative binding site of the gamma
      phosphate group of ATP.

PMID- 11469860
TI  - Ketoconazole-induced conformational changes in the active site of cytochrome
      P450eryF.
AB  - The azole-based P450 inhibitor ketoconazole is used to treat fungal infections
      and functions by blocking ergosterol biosynthesis in yeast. Ketoconazole binds to
      mammalian P450 enzymes and this can result in drug-drug interactions and lead to
      liver damage. To identify protein-drug interactions that contribute to binding
      specificity and affinity, we determined the crystal structure of ketoconazole
      complexed with P450eryF. In the P450eryF/ketoconazole structure, the azole moiety
      and nearby rings of ketoconzole are positioned in the active site similar to the
      substrate, 6-deoxyerythronolide B, with the azole nitrogen atom coordinated to
      the heme iron atom. The remainder of the ketoconazole molecule extends into the
      active-site pocket, which is occupied by water in the substrate complex. Binding
      of ketoconazole led to unexpected conformational changes in the I-helix. The I
      helix cleft near the active site has collapsed with a helical pitch of 5.4 A
      compared to 6.6 A in the substrate complex. P450eryF/ketoconazole crystals soaked
      in 6-deoxyerythronolide B to exchange ligands exhibit a structure identical with
      that of the original P450eryF/substrate complex, with the I-helix cleft restored
      to a pitch of 6.6 A. These findings indicate that the I-helix region of P450eryF
      is flexible and can adopt multiple conformations. An improved understanding of
      the flexibility of the active-site region of cytochrome P450 enzymes is important
      to gain insight into determinants of ligand binding/specificity as well as to
      evaluate models for catalytic mechanism based on static crystal structures.

PMID- 11469861
TI  - Interplay between an AAA module and an integrin I domain may regulate the
      function of magnesium chelatase.
AB  - In chlorophyll biosynthesis, insertion of Mg(2+) into protoporphyrin IX is
      catalysed in an ATP-dependent reaction by a three-subunit (BchI, BchD and BchH)
      enzyme magnesium chelatase. In this work we present the three-dimensional
      structure of the ATP-binding subunit BchI. The structure has been solved by the
      multiple wavelength anomalous dispersion method and refined at 2.1 A resolution
      to the crystallographic R-factor of 22.2 % (R(free)=24.5 %). It belongs to the
      chaperone-like "ATPase associated with a variety of cellular activities" (AAA)
      family of ATPases, with a novel arrangement of domains: the C-terminal helical
      domain is located behind the nucleotide-binding site, while in other known AAA
      module structures it is located on the top. Examination by electron microscopy of
      BchI solutions in the presence of ATP demonstrated that BchI, like other AAA
      proteins, forms oligomeric ring structures. Analysis of the amino acid sequence
      of subunit BchD revealed an AAA module at the N-terminal portion of the sequence
      and an integrin I domain at the C terminus. An acidic, proline-rich region
      linking these two domains is suggested to contribute to the association of BchI
      and BchD by binding to a positively charged cleft at the surface of the
      nucleotide-binding domain of BchI. Analysis of the amino acid sequences of BchI
      and BchH revealed integrin I domain-binding sequence motifs. These are proposed
      to bind the integrin I domain of BchD during the functional cycle of magnesium
      chelatase, linking porphyrin metallation by BchH to ATP hydrolysis by BchI. An
      integrin I domain and an acidic and proline-rich region have been identified in
      subunit CobT of cobalt chelatase, clearly demonstrating its homology to BchD.
      These findings, for the first time, provide an insight into the subunit
      organisation of magnesium chelatase and the homologous colbalt chelatase.

PMID- 11469862
TI  - Lateral recognition of a dye hapten by a llama VHH domain.
AB  - Camelids, camels and llamas, have a unique immune system able to produce heavy
      chain only antibodies. Their VH domains (VHHs) are the smallest binding units
      produced by immune systems, and therefore suitable for biotechnological
      applications through heterologous expression. The recognition of protein antigens
      by these VHHs is rather well documented, while less is known about the VHH/hapten
      interactions. The recently reported X-ray structure of a VHH in complex with a
      copper-containing azo-dye settled the ability of VHH to recognize haptens by
      forming a cavity between the three complementarity-determining regions (CDR).
      Here we report the structures of a VHH (VHH A52) free or complexed with an azo
      dye, RR1, without metal ion. The structure of the complex illustrates the
      involvement of CDR2, CDR3 and a framework residue in a lateral interaction with
      the hapten. Such a lateral combining site is comparable to that found in
      classical antibodies, although in the absence of the VL.

PMID- 11469863
TI  - The crystal and molecular structure of a collagen-like peptide with a
      biologically relevant sequence.
AB  - A detailed description of the 2.0 A structure of the triple-helical peptide, (Pro
      Hyp-Gly)(3)-Ile-Thr-Gly-Ala-Arg-Gly-Leu-Ala-Gly-Pro-Hyp-Gly-(Pro-Hyp-Gly)(3),
      denoted as T3-785, is presented. This peptide contains a biologically relevant
      sequence and was designed to model the imino acid-poor 785-796 region of human
      type III collagen just C-terminal to the matrix metalloproteinase cleavage site.
      The crystal structure of the T3-785 peptide demonstrates that sequence can
      influence local conformational changes in triple-helical structure, in terms of
      superhelical pitch, hydrogen bonding pattern, and hydration patterns. The novel
      packing arrangement displayed by the T3-785 structure, compared with those of
      collagen-like peptides with more imino acid-rich sequences indicates the sequence
      dependence of intermolecular assemblies in collagen as well. The observed synergy
      between the packing arrangements and the extended hydration network indicates
      that hydration of the triple helix is directly related to its association with
      other molecules.

PMID- 11469864
TI  - NMR evidence for mechanical coupling of phosphate B(I)-B(II) transitions with
      deoxyribose conformational exchange in DNA.
AB  - The conformational exchange of the phosphate and deoxyribose groups of the DNA
      oligomers d(GCGTACGC)(2) and d(CGCTAGCG)(2) have been investigated using a
      combination of homonuclear and heteronuclear NMR techniques. Two-state exchange
      between phosphate B(I) and B(II) conformations and deoxyribose N and S
      conformations was expressed as percent population of the major conformer, %B(I)
      or %S. Sequence context-dependent variations in %B(I) and %S were observed. The
      positions of the phosphate and deoxyribose equilibria provide a quantitative
      measure of the ps to ns timescale dynamic exchange processes in the DNA backbone.
      Linear correlations between %B(I), %S, and previously calculated model free (13)C
      order parameters (S(2)) were observed. The %B(I) of the phosphates were found to
      be correlated to the S(2) of the flanking C3' and C4' atoms. The %B(I) was also
      found to be correlated with the %S and C1' S(2) of the deoxyribose ring 5' of the
      phosphates. The %B(I) of opposing phosphates is correlated, while the %B(I) of
      sequential phosphates is anti-correlated. These correlations suggest that
      conformational exchange processes in DNA are coupled to each other and are
      modulated by DNA base sequence, which may have important implications for DNA
      protein interactions.

PMID- 11469865
TI  - Solution structure of the third immunoglobulin domain of the neural cell adhesion
      molecule N-CAM: can solution studies define the mechanism of homophilic binding?
AB  - Homophilic binding of the neural cell adhesion molecule (N-CAM) mediates the
      calcium-independent cell-cell adhesion that is involved in neuronal development.
      Two hypotheses have been advanced for the mechanism of homophilic binding. Cell
      based experiments have implicated each of the five extracellular immunoglobulin
      (Ig) domains of N-CAM in the homophilic adhesion interaction, and have predicted
      that the third domain (Ig III) self-associates. The alternative hypothesis is
      based on solution observations, which implicate a specific antiparallel
      interaction between the first two Ig domains (Ig I and Ig II). In order to test
      these hypotheses, we have determined a high-resolution solution structure of
      recombinant Ig III (sequence derived from chicken N-CAM) and examined the
      aggregation behavior of isolated Ig domains in solution. The structure shows that
      Ig III adopts a canonical Ig fold, in which the beta strands ABED and A'GFCC'
      form two beta sheets that are linked by a disulfide bond. In contrast to the
      demonstrated aggregation of Ig III on solid supports, we were unable to
      demonstrate self-association of Ig III under any of a variety of solution
      conditions. The structure shows that the surface of Ig III is dominated by two
      large acidic patches, which may explain our failure to observe self-association
      in solution. To evaluate the involvement of the Ig I-Ig II interaction in cell
      cell adhesion, we designed a point mutation in Ig I (F19S) that proved sufficient
      to abrogate the Ig I-Ig II interaction seen in solution. However, the
      introduction of this mutation into full-length N-CAM expressed in COS-7 cells
      failed to affect N-CAM-mediated cell-cell adhesion. The inability to observe Ig
      III self-association in solution, combined with the failure of the F19S mutation
      to affect N-CAM-mediated cell-cell adhesion, suggests that, although solution
      studies can give important insights into the structures of individual domains,
      the interactions observed in solution between the domains may not be
      representative of the interactions that occur on the cell surface.

PMID- 11469866
TI  - Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of
      cytotoxicity.
AB  - In expanded CAG repeat diseases such as Huntington's disease, proteins containing
      polyglutamine (poly(Gln)) sequences with repeat lengths of about 37 residues or
      more are associated with development of both disease symptoms and neuronal
      intranuclear inclusions (NIIs). Disease physiology in animal and cellular models
      does not always correlate with NII formation, however, and the mechanism by which
      aggregate formation might lead to cytotoxicity is unknown. To help evaluate
      various possible mechanisms, we determined the biophysical properties of a series
      of simple poly(Gln) peptides. The circular dichroism spectra of poly(Gln)
      peptides with repeat lengths of five, 15, 28 and 44 residues are all nearly
      identical and are consistent with a high degree of random coil structure,
      suggesting that the length-dependence of disease is not related to a
      conformational change in the monomeric states of expanded poly(Gln) sequences. In
      contrast, there is a dramatic increase in both the kinetics and the thermodynamic
      favorability of the spontaneous formation of ordered, amyloid-like aggregates for
      poly(Gln) peptides with repeat lengths of greater than 37 residues. At the same
      time, poly(Gln) peptides with repeat lengths in the 15-20 residue range, despite
      their poor abilities to support spontaneous, self-nucleated aggregation, are
      capable of efficiently adding to an already-formed aggregate. We also find that
      morphologically small, finely divided aggregates are much more efficient at
      recruiting poly(Gln) peptides than are large aggregates, suggesting a possible
      explanation for why disease pathology does not always correlate with the
      observable NII burden. Together, these data are consistent with a model for
      disease pathology in which critical cellular proteins possessing poly(Gln)
      sequences of modest length become inactivated when they are recruited into
      aggregates of an expanded poly(Gln) protein.

PMID- 11469867
TI  - Excluded volume in protein side-chain packing.
AB  - The excluded volume occupied by protein side-chains and the requirement of high
      packing density in the protein interior should severely limit the number of side
      chain conformations compatible with a given native backbone. To examine the
      relationship between side-chain geometry and side-chain packing, we use an all
      atom Monte Carlo simulation to sample the large space of side-chain
      conformations. We study three models of excluded volume and use umbrella sampling
      to effectively explore the entire space. We find that while excluded volume
      constraints reduce the size of conformational space by many orders of magnitude,
      the number of allowed conformations is still large. An average repacked
      conformation has 20 % of its chi angles in a non-native state, a marked reduction
      from the expected 67 % in the absence of excluded volume. Interestingly, well
      packed conformations with up to 50 % non-native chi angles exist. The repacked
      conformations have native packing density as measured by a standard Voronoi
      procedure. Entropy is distributed non-uniformly over positions, and we partially
      explain the observed distribution using rotamer probabilities derived from the
      Protein Data Bank database. In several cases, native rotamers that occur
      infrequently in the database are seen with high probability in our simulation,
      indicating that sequence-specific excluded volume interactions can stabilize
      rotamers that are rare for a given backbone. In spite of our finding that 65 % of
      the native rotamers and 85 % of chi(1) angles can be predicted correctly on the
      basis of excluded volume only, 95 % of positions can accommodate more than one
      rotamer in simulation. We estimate that, in order to quench the side-chain
      entropy observed in the presence of excluded volume interactions, other
      interactions (hydrophobic, polar, electrostatic) must provide an additional
      stabilization of at least 0.6 kT per residue in order to single out the native
      state.

PMID- 11469868
TI  - Ciprofloxacin affects conformational equilibria of DNA gyrase A in the presence
      of magnesium ions.
AB  - The conformational equilibria of the A subunit of DNA gyrase (GyrA), of its 59
      kDa N-terminal fragment (GyrA59) and of the quinolone-resistant Ser-Trp83 mutant
      (GyrATrp83), were investigated in the presence of mono- and divalent metal ions
      and ciprofloxacin, a clinically useful antibacterial quinolone. The stability of
      the proteins was estimated from temperature denaturation, monitoring unfolding
      with circular dichroism spectroscopy. Two transitions were observed in GyrA and
      GyrATrp83, which likely reflect unfolding of the N and C-terminal protein
      domains. Accordingly, one thermal transition is observed for GyrA59. The melting
      profile of the GyrA subunit is dramatically affected by monovalent and divalent
      metal ions, both transitions being shifted to lower temperature upon increasing
      salt concentration. This effect is much more pronounced with divalent ions
      (Mg(2+)) and cannot be accounted for by changes in ionic strength only. The
      presence of ciprofloxacin shifts the melting transitions of the wild-type subunit
      to higher temperatures when physiological concentrations of Mg(2+) are present.
      In contrast, both the mutant protein and the 59 kDa fragment do not show evidence
      for quinolone-driven changes. These data suggest that ciprofloxacin binds to the
      wild-type subunit in an interaction that involves Ser83 of GyrA and that both C
      and N-terminal domains may be required for effective drug-protein interactions.
      The bell-shaped dependence of the binding process upon Mg(2+) concentration, with
      a maximum centred at 3-4 mM [Mg(2+)], is consistent with a metal-ion mediated
      GyrA-quinolone-interaction. Affinity chromatography data fully support these
      findings and additionally confirm the requirement for a free carboxylate to
      elicit binding of the quinolone to GyrA. We infer that the Mg(2+)-GyrA
      interaction at physiological metal ion concentration could bear biological
      relevance, conferring more conformational flexibility to the active enzyme. The
      results obtained in the presence of ciprofloxacin additionally suggest that the
      Mg(2+)-mediated quinolone binding to the enzyme might be involved in the
      mechanism of action of this family of drugs.

PMID- 11469869
TI  - Yeast cytoplasmic and mitochondrial methionyl-tRNA synthetases: two structural
      frameworks for identical functions.
AB  - The yeast Saccharomyces cerevisiae possesses two methionyl-tRNA synthetases
      (MetRS), one in the cytoplasm and the other in mitochondria. The cytoplasmic
      MetRS has a zinc-finger motif of the type Cys-X(2)-Cys-X(9)-Cys-X(2)-Cys in an
      insertion domain that divides the nucleotide-binding fold into two halves,
      whereas no such motif is present in the mitochondrial MetRS. Here, we show that
      tightly bound zinc atom is present in the cytoplasmic MetRS but not in the
      mitochondrial MetRS. To test whether the presence of a zinc-binding site is
      required for cytoplasmic functions of MetRS, we constructed a yeast strain in
      which cytoplasmic MetRS gene was inactivated and the mitochondrial MetRS gene was
      expressed in the cytoplasm. Provided that methionine-accepting tRNA is
      overexpressed, this strain was viable, indicating that mitochondrial MetRS was
      able to aminoacylate tRNA(Met) in the cytoplasm. Site-directed mutagenesis
      demonstrated that the zinc domain was required for the stability and consequently
      for the activity of cytoplasmic MetRS. Mitochondrial MetRS, like cytoplasmic
      MetRS, supported homocysteine editing in vivo in the yeast cytoplasm. Both MetRSs
      catalyzed homocysteine editing and aminoacylation of coenzyme A in vitro. Thus,
      identical synthetic and editing functions can be carried out in different
      structural frameworks of cytoplasmic and mitochondrial MetRSs.

PMID- 11469870
TI  - Functional determinants of the Epstein-Barr virus protease.
AB  - Herpesvirus proteases are essential for the production of progeny virus. They
      cleave the assembly protein that fills the immature capsid in order to make place
      for the viral DNA. The recombinant protease of the human gamma-herpesvirus
      Epstein-Barr virus (EBV) was expressed in Escherichia coli and purified. Circular
      dichroism indicated that the protein was properly folded with a secondary
      structure content similar to that of other herpesvirus proteases. Gel filtration
      and sedimentation analysis indicated a fast monomer-dimer equilibrium of the
      protease with a K(d) of about 60 microM. This value was not influenced by
      glycerol but was lowered to 1.7 microM in the presence of 0.5 M sodium citrate.
      We also developed an HPLC-based enzymatic assay using a 20 amino acid residue
      synthetic peptide substrate derived from one of the viral target sequences for
      the protease. We found that conditions that stabilised the dimer also led to a
      higher enzymatic activity. Through sequential deletion of amino acid residues
      from either side of the cleavage site, the minimal peptide substrate for the
      protease was determined as P5-P2'. This minimal sequence is shorter than that for
      other herpesvirus proteases. The implications of our findings are discussed with
      reference to the viral life-cycle. These results are the first ever published on
      the EBV protease and represent a first step towards the development of protease
      inhibitors.

PMID- 11469872
TI  - Intracrystalline proteins and the hidden ultrastructure of calcium oxalate
      urinary crystals: implications for kidney stone formation.
AB  - The external appearance of urinary calcium oxalate (CaOx) crystals suggests that
      they are solid, homogeneous structures, despite their known association with
      proteins. Our aim was to determine whether proteins comprising the organic matrix
      of CaOx crystals are superficial or intracrystalline in order to clarify the role
      of urinary proteins in the formation of kidney stones. CaOx crystals were
      precipitated from centrifuged and filtered, or ultrafiltered, healthy human
      urine. They were then treated with dilute NaOH to remove bound proteins,
      partially demineralized with EDTA, or fractured and subjected to limited
      proteolysis before examination by low-resolution scanning electron microscopy or
      field emission scanning electron microscopy. Crystals precipitated from
      centrifuged and filtered urine had a complex interior network of protein
      distributed throughout the mineral phase, which appeared to comprise closely
      packed subcrystalline particles stacked in an orderly array among an amorphous
      organic matrix. This ultrastructure was not evident in crystals deposited in the
      absence of macromolecules, which were completely solid. This is the first direct
      evidence that crystals generated from cell-free systems contain significant
      amounts of protein distributed throughout a complex internal cribriform
      ultrastructure. Combined with mineral erosion in the acidic lysosomal
      environment, proteins inside CaOx crystals would render them susceptible to
      attack by urinary and intracellular renal proteases and facilitate their further
      dissolution or disruption into small particles and ions for removal by
      exocytosis. The findings also have broader ramifications for industry and the
      materials sciences, as well as the development and resorption of crystals in
      biomineralization systems throughout nature.

PMID- 11469873
TI  - A corrected quaternary arrangement of the peptidase HslV and atpase HslU in a
      cocrystal structure.
AB  - The bacterial heat shock locus HslU ATPase and HslV peptidase together form an
      ATP-dependent HslVU protease. Crystal structures show that HslU forms a hexamer
      with a pore at one end and HslV forms a dodecamer with translocation pores at
      both ends of two back-to-back stacked hexameric rings. Consistent with three
      electron microscopic studies and one small-angle X-ray scattering study, three
      crystal structures show that the nucleotide-binding domains of HslU bind to HslV
      and that the pores of the peptidase and ATPase are next to each other and
      aligned. A fourth crystal structure shows a radically different quaternary
      arrangement. Here I present a crystallographic analysis of the fourth structure
      to show that it contained a crystallographic origin shift and a mistake in space
      group assignment. Once these errors are corrected, a quaternary arrangement that
      is similar to those observed in the other structures emerges.

PMID- 11469874
TI  - The nature of siliceous mosaics forming the first shell of the brachiopod
      Discinisca.
AB  - The juvenile shell of the brachiopod Discinisca consists of a mosaic of
      micrometer-sized siliceous tablets embedded in a chitinous substrate. The first
      formed tablets are secreted on glycocalyx by a newly differentiated collective of
      outer epithelial cells. They are mainly rhombic but may also be ellipsoidal,
      discoidal, or deformed and sporadically overlap one another. On the surrounding
      juvenile shell, secreted by an incipient outer mantle lobe, the tablets are
      nearly all perfect rhombic plates in rhombic arrays. Their constant size,
      arrangement, and centripetal crystallization suggest intracellular assembly. The
      tablets, which are normally bilamellar, consist of discrete aggregates of
      crystalline spherules of silica in rhombic arrays within an organic matrix of
      fibrous protein and, presumably, a soluble polysaccharide(s). Mosaic secretion
      ceases at about the time when juveniles settle on the sea bed, which more or less
      coincides with the secretion of a ring of lamellae around the mosaic, induced by
      rapid advances and retractions of the outer mantle lobe prior to deposition of
      the organophosphatic mature shell. Energy dispersion X-ray analyses of pelagic
      and newly settled juveniles show that phosphatic secretion, even in the site of
      the first-formed outer epithelial collective, does not begin until all siliceous
      secretion has ceased.

PMID- 11469875
TI  - Three-dimensional electron microscopy of the clamp loader small subunit from
      Pyrococcus furiosus.
AB  - An archaeal clamp loader, replication factor C (RFC), consists of two proteins,
      the small subunit (RFCS) and large subunit (RFCL), whose sequences are both
      highly homologous to those of the eukaryotic RFC components. We have investigated
      the oligomeric structure of RFCS from Pyrococcus furiosus by electron microscopy
      using single-particle analysis. RFCS forms mostly ring-shaped hexamers at pH 9.0,
      although it tends to form C-shaped tetramers or pentamers at a lower pH (pH 5.5).
      The three-dimensional (3D) structure of the RFCS hexamer was obtained by random
      conical tilt reconstruction at 24.0-A resolution. RFCS forms a hexameric ring
      with outer and inner diameters of 117 and 27 A, respectively, and with a height
      of about 55 A. The six subunits are arranged in a twisted manner with a sixfold
      symmetry around the channel. The 3D map revealed that the six subunits are
      arranged in a head-to-tail configuration. Although the RFC complex consists of
      RFCS and RFCL in vivo, RFCS alone, together with PCNA, substantially enhanced the
      DNA synthesizing activity of P. furiosus DNA polymerase I in vitro. The 3D
      reconstruction of RFCS with catalytic activity provides important insights into
      the organization mechanism and the functional state of the RFC complex.

PMID- 11469876
TI  - Two-dimensional assembly of pentameric rabbit C-reactive proteins on lipid
      monolayers.
AB  - The problem of pentamer packing on a two-dimensional plane is of concern not only
      in physics and mathematics but also in biology. The packing styles of pentamers
      may either be related to or reflect the physiological or biochemical properties
      of biological macromolecules. C-reactive protein (CRP), one of the classical
      members of the petraxin family, was recently two-dimensionally (2D) crystallized
      by us on lipid monolayers by specific adsorption (Wang, H. W., and Sui, S. F.,
      1999, J. Struct. Biol. 127, 283-286). Another type of the protein's 2D crystal
      under the same conditions was obtained in the present work. The new 2D crystal
      was studied using electron microscopy of negatively stained specimens followed by
      image processing. A projection map at 2.2-nm resolution was obtained. The
      previous 2D crystal (PI) and the current 2D crystal (PII) show different pentamer
      packing styles. Both of them are closely related to the fivefold symmetry of the
      molecule itself. The coexistence and the spatial contiguity of the two types of
      pentamer assembly were observed in a visual field. The fivefold symmetrical
      macromolecule can form a pentiling pattern on a two-dimensional plane, which has
      never been reported in biological system before. The possible mechanism of the
      two-dimensional assembly of pentameric CRP on lipid monolayers is discussed.

PMID- 11469877
TI  - Proteins and saccharides of the sea urchin organic matrix of mineralization:
      characterization and localization in the spine skeleton.
AB  - Properties of the echinoderm skeleton are under biological control, which is
      exerted in part by the organic matrix embedded in the mineralized part of the
      skeleton. This organic matrix consists of proteins and glycoproteins whose
      carbohydrate component is specifically involved in the control mechanisms. The
      saccharide moiety of the organic matrix of the spines of the echinoid
      Paracentrotus lividus was characterized using enzyme-linked lectin assays
      (ELLAs). O-glycoproteins, different types of complex N-glycoproteins, and
      terminal sialic acids were detected. Sialic acids are known to interact with Ca
      ions and could play an important role in the mineralization process. Some of the
      carbohydrate components detected by ELLAs as well as two organic matrix proteins
      (SM30 and SM50) were localized within different subregions of the spine skeleton
      using field-emission scanning electron microscopy. The mappings show that some of
      these components are not homogeneously distributed in the different skeletal
      subregions. For example, some N-glycoproteins were preferentially located in the
      putative amorphous subregion of the skeleton, whereas some O-glycoproteins were
      localized in the subregion where skeletal growth is inhibited. These results
      suggest that the biological control exerted on the skeletal properties can be
      partly modulated by local differences in the organic matrix composition.

PMID- 11469878
TI  - Membrane dips over nuclei correlate with DNA synthesis in spreading hepatocytes.
AB  - Spreading of hepatocytes on different supports was examined using scanning
      electron microscopy. Positively charged Primaria plates gave a uniform morphology
      in 2 h. The spreading was rapid and the surface of the cells showed early
      prominent dips. The hepatocytes had one or two of these structures corresponding
      with nuclearity of the cells. The nuclear origin of the dips was confirmed after
      6 h. The indentations contained solid structures the number, size, and shape of
      which were identical to the nucleoli seen by light microscopy. The spreading on
      the other supports was less uniform. Nuclear dips appeared more slowly and were
      less marked initially in their depths. The nuclear dipping was independent of
      cell density and took place under conditions under which the cells undergo
      phenotypic changes during culture. Individual phenotypic changes occur at
      different times and rates so that the initial signal for their onset cannot be
      determined with any certainty. However, the appearance of the dips was
      accompanied by DNA synthesis in the normally quiescent cells. The process stopped
      when the dipping was completed. The unavoidable change in nuclear morphology in
      spread cells may explain why maintenance of a spherical shape circumvents
      inappropriate DNA synthesis and maintains hepatocyte differentiation in vitro.

PMID- 11469879
TI  - DNA in human and stallion spermatozoa forms local hexagonal packing with twist
      and many defects.
AB  - In human and other mammal sperm nuclei, DNA is packed in a highly condensed
      state, the structure of which remains unsolved. Cryoelectron microscopy of
      vitrified sections provides a first direct view of the local arrangement of the
      nucleoprotamine filament. DNA aligns in parallel in layers and its orientation
      rotates along a single-twist direction as in a cholesteric liquid crystal. The
      structure contains numerous defects, which introduce locally double-twist
      configurations. Destruction of the SS bonds with dithiotrehitol relaxes the twist
      and favors the extension of the hexagonal close packing of the filaments, though
      keeping constant their interfilament distance.

PMID- 11469880
TI  - Purification, crystallization, and preliminary X-ray diffraction analysis of the
      Tricorn protease hexamer from Thermoplasma acidophilum.
AB  - Tricorn protease from Thermoplasma acidophilum is a hexameric enzyme; in vivo the
      hexamers assemble further to form large icosahedral capsids of 14.6 MDa.
      Recombinant Tricorn protease was purified as an enzymatically active hexamer of
      0.72 MDa that formed crystals of octahedral morphology under low-ionic-strength
      conditions. These crystals belong to space group C2 with unit cell dimensions a =
      307.5 A, b = 163.2 A, c = 220.9 A, beta = 105.5 degrees and diffract to 2.2-A
      resolution using high-brilliance synchrotron radiation. Based on analysis of the
      self-rotation function and the presence of a pseudo-origin peak in the native
      Patterson map, a packing model was derived for the complex, comprising 1.5
      hexamers per asymmetric unit with a solvent content of 43%. Due to the ninefold
      noncrystallographic symmetry the Tricorn crystals represent an interesting case
      for phasing X-ray crystallographic data by electron microscopic phase
      information.

PMID- 11469881
TI  - Crystallization and preliminary X-ray studies of V(1)-ATPase of Thermus
      thermophilus HB8 complexed with Mg-ADP.
AB  - Crystals have been grown of the V(1)-ATPase sector of the V-type ATP synthase
      complex (V(0)V(1)) from the thermophilic eubacterium Thermus thermophilus HB8.
      These crystals are grown by the vapor diffusion method in the presence of 5 mM Mg
      ADP, from solutions containing 100 mM sodium acetate and 2 M sodium formate, pH
      5.5. The crystals diffracted X rays beyond 3.4 A in resolution on a synchrotron
      radiation source. The crystals belong to the trigonal space group P3, with unit
      cell dimensions of a = b = 89.0 A, c = 179.2 A, and gamma = 120 degrees. The unit
      cell presumably contains one molecule of V(1)-ATPase and the V(m) value is
      calculated as 3.0 A(3)/Da.

PMID- 11469882
TI  - Can expression of apoptosis genes, bcl-2 and bax, predict survival and
      responsiveness to chemotherapy in node-negative breast cancer patients?
AB  - BACKGROUND: Although the status of the axillary lymph nodes is widely accepted to
      be associated with prognosis in breast cancer patients, there is a need for
      biomarkers to be analyzed as indicators of responsiveness to treatment. The
      objective of this study was to test the hypothesis that the expression of
      apoptosis genes, bcl-2 and bax, predicts survival and responsiveness to
      chemotherapy in node-negative breast cancer patients. METHODS: One hundred thirty
      premenopausal women with primary breast carcinoma were studied for the expression
      of bcl-2 and bax genes. The relationship between the expression of bcl-2 and bax
      proteins and a series of markers of known prognostic value [such as tumor size,
      nuclear grade, receptors of the steroid hormones estrogen (ER) and progesterone
      (PgR)]. The association of these proteins with survival and responsiveness to
      chemotherapy was also examined. RESULTS: Sixty (46%) and sixty-four (49%) breast
      cancer cases were found positive for bcl-2 and bax, respectively, as indicated by
      immunohistochemistry. A statistically significant association was found between
      expression of bcl-2 and tumor size (P = 0.001), low grade (grade I) (P = 0.002),
      positivity of ER (P = 0.001), positivity of PR (P = 0.03), and superior disease
      free survival (DFS) (P = 0.04), and superior overall survival (OS) (P = 0.03). In
      contrast, no similar associations were observed for the bax gene. Overall, there
      was a trend toward an association between adjuvant chemotherapy and DFS (P =
      0.08) and OS (P = 0.07). This trend became statistically significant when the
      patients were analyzed by individual gene expression. In bax-positive patients,
      chemotherapy improves 6-year DFS (P = 0.01) and OS (P = 0.03) while similar
      effects were not observed in the other subgroups of patients. CONCLUSION: Our
      results indicated that bcl-2 expression is associated with a number of favorable
      prognostic factors and better clinical outcome, while bax expression seems to
      have positive predictive value for responsiveness to chemotherapy in lymph node
      negative breast cancer patients.

PMID- 11469883
TI  - An original technique for bladder autoaugmentation with protective abdominal
      rectus muscle flaps: an experimental study in rats.
AB  - BACKGROUND: Bladder autoaugmentation uses partial detrusorectomy to create a
      diverticular bulge in the bladder mucosa. This technique has eliminated certain
      serious complications of cystoplasty with gastrointestinal tissues (e.g.,
      fluid/electrolyte/acid-base imbalances, mucous hypersecretion), but the exposed
      mucosa is subject to fibrosis and, sometimes, to perforation, which can annul the
      benefits of surgery. METHODS: We have developed an original technique based on
      traditional autoaugmentation with protection of the herniated mucosa by split
      thickness pedunculated rectus abdominis muscle flaps that are sutured to the
      incised margins of the detrusor. Preliminary testing was done on 30 adult Wistar
      rats. A control group of 15 rats underwent laparotomy alone. Bladder capacity was
      measured via suprapubic cystography before and after (4 weeks, 8 weeks, 1 year)
      surgery, just before sacrifice. Sections of the reconstructed bladder were
      examined histologically. RESULTS: Twenty-three bladder-augmented rats and 13
      controls survived. In the experimental group, bladder capacity increased by 38%
      (mean). None of the rats experienced urinary retention, although one developed
      bladder stones. Histology revealed no pathologic changes (other than chronic
      inflammatory infiltrates at suture sites) in the mucosa, detrusor, or muscle
      flaps, which were all viable and well integrated by the fourth postoperative
      week. There were no signs of mucosal or muscle fibrosis. CONCLUSIONS: Preliminary
      results in a rat model suggest that this new technique can produce an enlarged
      bladder that is fully functional and less vulnerable to fibrotic retraction and
      rupture. Residual contractility in the muscle flaps might theoretically be
      exploited to facilitate paraphysiologic micturition.

PMID- 11469884
TI  - Delivery and scavenging system for small animal inhalational anesthesia.
AB  - BACKGROUND: Inhalational agents have been widely used for anesthesia in
      laboratory animals. However, the safe use of inhalational agents in small
      laboratory animals has been limited by the lack of a suitable and effective
      scavenging system for the removal of waste anesthetic gases. The aim of the
      present study is to develop an anesthetic system that can be manufactured using
      common household and laboratory items. MATERIALS AND METHODS: An anesthetic
      system was designed for rats weighing from 300 to 350 g. A face mask for the rat
      was made by cutting off the distal part of a 50-ml centrifuge tube. A scavenging
      hood was made from a transparent plastic food storage box. Exhaust of anesthetic
      gases from the scavenger hood was facilitated by fitting an outlet connected to a
      pump. Four experienced researchers or technicians tested the scavenger hood.
      RESULTS: In 79.2% of the trials the participants could smell halothane when the
      pump from the scavenger system was not operational. However, when the pump was
      switched on, halothane was detected only 16.7% of the time (P < 0.001).
      CONCLUSION: We have developed a simple and effective method of delivering
      inhalational anesthesia to small laboratory animals and of removing waste
      anesthetic gases.

PMID- 11469885
TI  - Mechanisms of taxotere-related drug resistance in pancreatic carcinoma.
AB  - BACKGROUND: Pancreatic adenocarcinoma (PAC) is generally refractory to most
      chemotherapeutic agents, including docetaxel (Taxotere; TXT). Specific mechanisms
      for TXT-related drug resistance in PAC have not been defined. The hypothesis of
      this study was that PAC resistance to TXT is primarily related to P-glycoprotein
      (P-gp), the expression product of multiple drug resistance (MDR)-1, as opposed to
      lung resistance protein (LRP) or multidrug resistance protein (MRP). MATERIALS
      AND METHODS: The sensitivity of the PAC cell line SUIT-2 and its sublines to TXT,
      doxorubicin (DOX) and 5-fluorouracil (5-FU) was evaluated with a 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. MDR1 (P-gp), MRP,
      LRP, and beta-tubulin isotype gene expressions were detected at the messenger RNA
      level by reverse transcription-polymerase chain reaction (RT-PCR). Verapamil and
      indomethacin (IMC) were used to test the functionality of P-gp and MRP,
      respectively. RESULTS: The SUIT-2 subline S-020 and the TXT-selected SUIT-2 cell
      line S2/TXT were significantly resistant to TXT. Both showed cross-resistance to
      DOX but no resistance to 5-FU. RT-PCR demonstrated strong expression of P-gp in S
      020 and S2/TXT and weaker or no expression in other cells lines. MRP and LRP
      expression was found in most of these cell lines but had no relationship to the
      TXT resistance. TXT resistance in S2-020 and S2/TXT could be reversed by
      verapamil but not by IMC. Levels of beta-tubulin isotype II and III were
      increased in S2/TXT compared with S-020 and SUIT-2. CONCLUSIONS: Intrinsic and
      acquired TXT resistance is primarily mediated by P-gp, but not by MRP or LRP, and
      is markedly reversed by the P-gp modulator verapamil. Hence future related
      studies should focus on the use of agents that block the transporter action of P
      gp.

PMID- 11469886
TI  - Suppression of tumor necrosis factor alpha production by cAMP in human monocytes:
      dissociation with mRNA level and independent of interleukin-10.
AB  - BACKGROUND: Elevation of cellular cAMP inhibits lipopolysaccharide(LPS)
      stimulated tumor necrosis factor alpha (TNF-alpha) production and increases the
      expression of interleukin (IL)-10 in mononuclear cells. TNF-alpha gene expression
      obligates activation of the transcription factor nuclear factor kappaB (NF
      kappaB). Exogenous IL-10 inhibits NF-kappaB in monocytes and thus attenuates TNF
      alpha production. We examined the role of endogenous IL-10 in the regulation of
      NF-kappaB activation and TNF-alpha production in human monocytes by cAMP.
      METHODS: Human monocytes were stimulated with Escherichia coli LPS (100 ng/ml)
      with and without forskolin (FSK, 50 microM) or dibutyryl cyclic AMP (dbcAMP, 100
      microM). Cytokine (TNF-alpha and IL-10) release was measured by immunoassay. TNF
      alpha mRNA was measured by reverse transcription polymerase chain reaction, and
      NF-kappaB DNA binding activity was assessed by gel mobility shift assay. RESULTS:
      cAMP-elevating agents inhibited LPS-stimulated TNF-alpha release (0.77 +/- 0.13
      ng/10(6) cells in LPS + dbcAMP and 0.68 +/- 0.19 ng/10(6) cells in LPS + FSK,
      both P < 0.05 vs 1.61 +/- 0.34 ng/10(6) cells in LPS alone). Conversely, cAMP
      enhanced LPS-stimulated IL-10 release (100 +/- 21.5 pg/10(6) cells in LPS +
      dbcAMP and 110 +/- 25.2 pg/10(6) cells in LPS + FSK, both P < 0.05 vs 53.3 +/-
      12.8 pg/10(6) cells in LPS alone). Neither TNF-alpha mRNA expression nor NF
      kappaB activation stimulated by LPS was inhibited by the cAMP-elevating agents.
      Neutralization of IL-10 with a specific antibody did not attenuate the effect of
      cAMP-elevating agents on TNF-alpha production. CONCLUSION: The results indicate
      that cAMP inhibits LPS-stimulated TNF-alpha production through a
      posttranscriptional mechanism that is independent of endogenous IL-10.

PMID- 11469887
TI  - A model for tracking student experiences on surgical clerkships.
AB  - This study was conducted to identify the range and nature of surgical clerkship
      experiences in three different hospital settings-university, community, and
      public. METHODS: An instrument was developed to track the location and type of
      learning experience, patient demographics, surgical content, and clinical
      experience of students on their surgical clerkship. Twenty-three students used
      the instrument to record the events of their surgical clerkship. Data were
      analyzed to describe the frequency of tasks performed, the nature and location of
      learning experience, exposure to surgical topics, and patient demographics.
      RESULTS: Students were involved in an average of 245 common surgical tasks over
      their 8-week clerkship. Of their exposure to common tasks, students had the
      opportunity to observe 25% and perform 70% of those tasks. Sixty-six percent of
      task work occurred on the patient floor and 23% occurred in the operating room.
      Students were exposed to a broad range of surgical topics, 71% of which were
      general surgery topics. Only 25% of these experiences were auditory, whereas 39%
      involved exposure to a patient, and 36% included participation in an operation.
      Patient load and characteristics tended to vary across hospital settings, and on
      average, students worked with 164 patients during their clerkship. The smallest
      patient load (m = 113) occurred in the university hospital and the largest
      patient load (m = 251) occurred in the public hospital. CONCLUSION: Although
      surgical services and hospital settings may offer students different clerkship
      experiences, the common clinical and didactic components of a surgical clerkship
      can balance a student's exposure to surgical topics and practice of clinical
      skills. Tracking surgical clerkship experiences is valuable in identifying the
      range and nature of medical students' didactic, clinical, and operative
      experiences.

PMID- 11469888
TI  - Inhibition of Kupffer cells reduced CXC chemokine production and liver injury.
AB  - BACKGROUND: Cytokine production is a critical component of ischemia/reperfusion
      (IR) injury. In the liver, Kupffer cells produce cytokines and chemokines (i.e.,
      cytokines with chemoattractant properties) that are important mediators in
      neutrophil recruitment and subsequent hepatocellular injury. Therefore, the role
      of Kupffer cells in chemokine production in hepatic IR injury was investigated.
      METHODS: Adult male C57BL/6 mice underwent 90 min of partial hepatic ischemia
      followed by various reperfusion times (i.e., 0, 1.5, 3, and 6 h). Gadolinium
      chloride (GC), which inhibits Kupffer cell activity, was administered to mice 48
      and 24 h prior to ischemia. The control group received a corresponding volume of
      normal saline. Plasma levels of the cytokine macrophage inflammatory protein-2
      (MIP-2), KC, and tumor necrosis factor (TNF)-alpha and liver mRNA were measured.
      Liver injury was assessed by plasma level of alanine transaminase (ALT) and
      histopathology. RESULTS: A reperfusion time-dependent liver injury occurred as
      indicated by increased levels of plasma ALT and histopathology. The injury was
      associated with increased plasma TNF-alpha, MIP-2, and KC and their hepatic mRNA
      expression and neutrophil infiltration into ischemic lobes of the liver. GC
      treatment significantly reduced the number of Kupffer cells as determined by the
      immunostained liver tissue sections. The extent of liver injury significantly
      decreased in GC-treated mice that were associated with decreased levels of plasma
      ALT, TNF-alpha, MIP-2, and KC and neutrophil infiltration. CONCLUSIONS: This
      study suggests that Kupffer cells are major contributors to cytokine production
      in hepatic IR and their modulation may serve as a potential target for
      therapeutic intervention.

PMID- 11469889
TI  - Autologous keratinocyte suspensions accelerate epidermal wound healing in pigs.
AB  - BACKGROUND: Tissue culture techniques enable in vitro expansion of keratinocytes
      that can be used to treat burns and chronic wounds. These keratinocytes are
      commonly grafted onto the wounds as differentiated sheets of mature epithelium.
      Less is however known about the effects of transplanting the cells as
      suspensions. This study evaluated epidermal regeneration in fluid-treated skin
      wounds treated with suspensions of cultured and noncultured autologous
      keratinocytes. MATERIALS AND METHODS: Eighty-seven full-thickness excisional skin
      wounds were created on the back of 6 pigs and then transplanted with either
      cultured or noncultured autologous keratinocytes. The wounds were enclosed with
      liquid-tight chambers containing saline to provide a hydrated and standardized
      environment. RESULTS: Keratinocyte transplantation resulted in several cell
      colonies within the granulation tissue of the wound. These colonies progressively
      coalesced and contributed to a new epithelium. The origin of the transplanted
      keratinocytes was confirmed by histochemical staining of wounds transplanted with
      transfected keratinocytes expressing beta-galactosidase. Transplantation of 0.125
      x 10(6), 0.5 x 10(6), and 2.0 x 10(6) cultured keratinocytes, and 0.5 x 10(6) and
      5.0 x 10(6) noncultured keratinocytes, increased reepithelialization dose
      dependently over saline-treated controls. The epithelial barrier function
      recovered faster in transplanted wounds as demonstrated by less protein leakage
      over the wound surface on Days 7-10 as compared to control wounds. Wound
      reepithelialization and the number of keratinocyte colonies observed in
      granulation tissue were significantly less in wounds transplanted with
      noncultured keratinocytes compared to wounds seeded with cultured keratinocytes.
      CONCLUSION: Our study demonstrates successful transplantation of keratinocyte
      suspensions and their dose-dependent acceleration of wound repair. Selection of
      proliferative cells during culture and higher colony-forming efficiency may
      explain the greater effects observed with cultured keratinocytes.

PMID- 11469890
TI  - Effects of ischemia on gene expression.
AB  - Microarray gene expression technology has recently made it feasible to
      characterize the RNA expression of thousands of genes across numerous tissue
      samples. We hypothesized that the warm ischemia commonly associated with the
      surgical extirpation of human tissue would have significant effects on gene
      expression profiles. To quantitate the effects of warm ischemia on human tissue,
      we rapidly dissected normal mucosa from a human colon cancer specimen. The
      specimen was divided and maintained at room temperature until snap-frozen in
      liquid nitrogen. Aliquots of tissue were frozen at times 5, 10, 15, 20, 40, and
      60 min after extirpation. Spotted microarrays composed of 2400 distinct elements
      were used to assay mRNA derived from each time point in triplicate. Eisen's
      hierarchical clustering methodology and Bayesean statistical methods were then
      used to assay the effects of warm ischemia on gene expression. Application of
      time-course statistical models suggest that three patterns were induced by
      ischemia, accounting for 68.2, 17.8, and 13.4% of the evaluable genes,
      respectively. Pattern I corresponds to an average change of 27% over 60 min from
      5 min baseline level of expression and 63.8% of the genes with at least 80%
      probability of membership in this pattern show average increases in expression
      over 60 min. The remainder decrease on average. Pattern II genes show the least
      ischemia-related effects, demonstrating an average change of only 12% over 60
      min. In contrast to pattern I, we find that 67.5% of the genes with at least 80%
      probability of membership in this pattern are decreasing in expression on average
      over time. The remaining 32.5% in this pattern increase an average of 12% over 60
      min. Finally, pattern III genes (13.4% of the sample) show the greatest
      sensitivity to ischemia, changing an average of 50% over 60 min, with about the
      same number increasing as are decreasing. Fold changes in RNA over- or under
      expression were observed up to greater than 20-fold. Warm ischemia associated
      with the surgical extirpation of human tissues has significant effects on gene
      expression. These data support the careful monitoring of ischemic time for
      tissues harvested for the purpose of gene profiling.

PMID- 11469891
TI  - Endothelial implants provide long-term control of vascular repair in a porcine
      model of arterial injury.
AB  - Cell culture and animal data support the role of endothelial cells and
      endothelial-based compounds in regulating vascular repair after injury. We
      describe a long-term study in pigs in which the biological and immunological
      responses to endothelial cell implants were investigated 3 months after
      angioplasty, approximately 2 months after the implants have degraded. Confluent
      porcine or bovine endothelial cells grown in polymer matrices were implanted
      adjacent to 28 injured porcine carotid arteries. Porcine and bovine endothelial
      cell implants significantly reduced experimental restenosis compared to control
      by 56 and 31%, respectively. Host humoral responses were investigated by
      detection of an increase in serum antibodies that bind to the bovine or porcine
      cell strains used for implantation. A significant increase in titer of
      circulating antibodies to the bovine cells was observed after 4 days in all
      animals implanted with xenogeneic cells. Detected antibodies returned to
      presurgery levels after Day 40. No significant increase in titer of antibodies to
      the porcine cells was observed during the time course of the experiment in
      animals implanted with porcine endothelial cells. No implanted cells, Gelfoam, or
      focal inflammatory reaction could be detected histologically at any of the
      implant sites at 90 days. These data suggest that tissue-engineered endothelial
      cell implants may provide long-term control of vascular repair after injury,
      rather than simply delaying lesion formation and that allogeneic implants are
      able to provide a greater benefit than xenogeneic implants.

PMID- 11469892
TI  - Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase
      activity during hemorrhage.
AB  - BACKGROUND: Recent evidence suggests that hyperlactatemia in shock may reflect
      accelerated aerobic glycolysis linked to activity of the Na(+), K(+)-ATPase
      rather than hypoxia. Epinephrine stimulates glycolysis in resting muscle largely
      by stimulating Na(+), K(+)-ATPase activity. This study evaluates the effects of
      hemorrhagic shock, with and without combined alpha- and beta-adrenergic receptor
      blockade, on lactate production, glycogenolysis, Na(+)-K(+) pump activity, and
      high-energy phosphates in rat skeletal muscle. METHODS: Male Sprague-Dawley rats
      in four treatment groups were studied: unhemorrhaged control not receiving
      blockers (CN), controls receiving blockers (CB), shocked animals not receiving
      blockers (SN), and shocked rats receiving blockers (SB). Shocked rats (SN and SB)
      were bled to a MAP of 40 mm Hg, maintained for 60 min. Blocker groups (CB and SB)
      received propranolol and phenoxybenzamine. Arterial blood was drawn for plasma
      lactate, epinephrine, norepinephrine, and gas analysis. Lactate, glycogen,
      glucose 6-phosphate, ATP, phosphocreatine, and intracellular Na(+) and K(+) were
      determined in extensor digitorum longus and soleus muscles. For comparison,
      muscles were exposed to epinephrine and/or ouabain in vitro. RESULTS: With the
      exception of P(a)CO(2), HCO(3), and base excess in the SN group, no significant
      differences in arterial blood gas parameters were noted. Adrenergic blockade
      significantly reduced plasma lactate concentration. In shocked rats, adrenergic
      blockade significantly reduced muscle lactate and glucose 6-phosphate
      accumulation. Intracellular Na(+):K(+) ratio was decreased in SN rats, implying
      increased Na(+)-K(+) pump activity. Adrenergic blockade raised the intracellular
      Na(+):K(+) ratio in shocked animals, implying decreased pump activity.
      Epinephrine exposure in vitro stimulated muscle lactate production, raised
      glucose 6-phosphate content, and significantly reduced soleus phosphocreatine
      stores. CONCLUSIONS: Neither hypoxia nor defective oxidative metabolism appeared
      responsible for increased glycolysis during hemorrhagic shock. Adrenergic
      blockade concurrently reduced plasma lactate, muscle levels of lactate and
      glucose 6-phosphate, and muscle Na(+)-K(+) pump activity during shock. Rapid
      skeletal muscle aerobic glycolysis in response to increased plasma epinephrine
      levels may be an important contributor to increased glycolysis in muscle and
      increased plasma lactate during hemorrhagic shock.

PMID- 11469893
TI  - Metalloproteinase inhibition prevents acute respiratory distress syndrome.
AB  - BACKGROUND: The acute respiratory distress syndrome (ARDS) occurs in patients
      with clearly identifiable risk factors, and its treatment remains merely
      supportive. We postulated that patients at risk for ARDS can be protected against
      lung injury by a prophylactic treatment strategy that targets neutrophil-derived
      proteases. We hypothesized that a chemically modified tetracycline 3 (COL-3), a
      potent inhibitor of neutrophil matrix metalloproteinases (MMPs) and neutrophil
      elastase (NE) with minimal toxicity, would prevent ARDS in our porcine endotoxin
      induced ARDS model. METHODS: Yorkshire pigs were anesthetized, intubated,
      surgically instrumented for hemodynamic monitoring, and randomized into three
      groups: (1) control (n = 4), surgical instrumentation only; (2)
      lipopolysaccharide (LPS) (n = 4), infusion of Escherichia coli lipopolysaccharide
      at 100 microg/kg; and (3) COL-3 + LPS (n = 5), ingestion of COL-3 (100 mg/kg) 12
      h before LPS infusion. All animals were monitored for 6 h following LPS or sham
      LPS infusion. Serial bronchoalveolar lavage (BAL) samples were analyzed for MMP
      concentration by gelatin zymography. Lung tissue was fixed for morphometric
      assessment at necropsy. RESULTS: LPS infusion was marked by significant (P <
      0.05) physiological deterioration as compared with the control group, including
      increased plateau airway pressure (P(plat)) (control = 15.7 +/- 0.4 mm Hg, LPS =
      23.0 +/- 1.5 mm Hg) and a decrement in arterial oxygen partial pressure
      (P(a)O(2)) (LPS = 66 +/- 15 mm Hg, Control = 263 +/- 25 mm Hg) 6 h following LPS
      or sham LPS infusion, respectively. Pretreatment with COL-3 reduced the above
      pathophysiological changes 6 h following LPS infusion (P(plat) = 18.5 +/- 1.7 mm
      Hg, P(a)O(2) = 199 +/- 35 mm Hg; P = NS vs control). MMP-9 and MMP-2
      concentration in BAL fluid was significantly increased between 2 and 4 h post-LPS
      infusion; COL-3 reduced the increase in MMP-9 and MMP-2 concentration at all time
      periods. Morphometrically LPS caused a significant sequestration of neutrophils
      and monocytes into pulmonary tissue. Pretreatment with COL-3 ameliorated this
      response. The wet/dry lung weight ratio was significantly greater (P < 0.05) in
      the LPS group (10.1 +/- 1.0 ratio) than in either the control (6.4 +/- 0.5 ratio)
      or LPS+COL-3 (7.4 +/- 0.6 ratio) group. CONCLUSIONS: A single prophylactic
      treatment with COL-3 prevented lung injury in our model of endotoxin-induced
      ARDS. The proposed mechanism of COL-3 is a synergistic inhibition of the terminal
      neutrophil effectors MMPs and NE. Similar to the universal practice of
      prophylaxis against gastric stress ulceration and deep venous thromboses in
      trauma patients, chemically modified tetracyclines may likewise be administered
      to prevent acute lung injury in critically injured patients at risk of developing
      ARDS.

PMID- 11469894
TI  - Effect of varying burn sizes and ambient temperature on the hypermetabolic rate
      in thermally injured rats.
AB  - BACKGROUND: Small animals with scald covering 50% of their total body surface
      area (TBSA) have been used to study the hypermetabolic burn response. In the 50%
      TBSA burn rat model, the area of normal skin that is available for animal
      instrumentation is restricted and the mortality rate has been high. The purpose
      of this study was to determine whether a smaller burn size can induce a similar
      hypermetabolic response with mortality rates lower than those of the 50% TBSA
      model. METHODS: Rats were randomly divided into four groups to receive a 0% (sham
      nonburned), 30%, 40%, or 50% TBSA third-degree scald burn. The hypermetabolic
      response was determined by measuring changes in body weight and oxygen
      consumption at ambient temperatures of 21, 26, and 31 degrees C for each burn
      size. Weight measurements were made daily while oxygen consumption was measured
      7, 11, and 14 days after thermal injury. RESULTS: All thermally injured rats lost
      body weight; however, there were no significant differences between the 30, 40,
      and 50% TBSA burn groups. Burn induced a hypermetabolic response as indicated by
      an increase in oxygen consumption from 130 to 200% that of sham nonburned rats.
      No significant difference in oxygen consumption could be shown over the study
      period between the three burn sizes at different ambient temperatures. Mortality
      was 0% in the sham and 30% group, 10% for the 40% group, and 50% for the 50% TBSA
      burn group. CONCLUSIONS: From our study we conclude that a burn size covering 30%
      of the TBSA induces the same hypermetabolic response as a 50% TBSA burn.

PMID- 11469895
TI  - cAMP inhibits inducible nitric oxide synthase expression and NF-kappaB-binding
      activity in cultured rat hepatocytes.
AB  - BACKGROUND: The inducible nitric oxide synthase (iNOS) is strongly expressed
      following inflammatory stimuli. Adenosine 3',5'-cyclic monophosphate (cAMP)
      increases iNOS expression and activity in a number of cell types but decreases
      cytokine-stimulated iNOS expression in hepatocytes. The mechanisms for this
      effect are unknown. METHODS: Rat hepatocytes were stimulated with cytokines to
      induce iNOS and cultured with cAMP agonists dibutyryl-cAMP (dbcAMP), 8-bromo
      cAMP, and forskolin (FSK). Nitric oxide synthesis was assessed by supernatant
      nitrite levels and iNOS expression was measured by Northern and Western blot
      analyses. Nuclear factor kappaB binding was assessed by electromobility shift
      assay. RESULTS: Cyclic AMP dose dependently decreased NO synthesis in response to
      a combination of proinflammatory cytokines or interleukin-1beta (IL-1beta) alone.
      The adenylate cyclase inhibitor SQ 22,536 increased cytokine- or IL-1beta
      stimulated NO synthesis. dbcAMP decreased iNOS mRNA expression and iNOS protein
      expression. Both dbcAMP and glucagon decreased iNOS promoter activity in rat
      hepatocytes transfected with the murine iNOS promoter and decreased DNA binding
      of the transcription factor NF-kappaB. CONCLUSION: These data suggest that cAMP
      is important in hepatocyte iNOS expression and agents that alter cAMP levels may
      profoundly alter the response of hepatocytes to inflammatory stimuli through
      effects onthe iNOS promoter region and NF-kappaB.

PMID- 11469896
TI  - Radiofrequency ablation for eradication of pulmonary tumor in rabbits.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has emerged as an alternative for
      surgery in clinical oncology. This animal experiment was conducted to evaluate
      the feasibility of RFA in the treatment of pulmonary tumor. METHODS: Eighteen
      rabbits with pulmonary implantation of VX2 tumors were divided into two groups.
      Group A (n = 12) was treated with RFA by using a cooled-tip electrode technique.
      Group B (n = 6) received sham operation. The therapeutic efficacy was evaluated
      by survival rate, magnetic resonance imaging (MRI), postmortem microangiography,
      and histology. RESULTS: All animals in group B died within 3 months after tumor
      implantation. Tumor eradication was achieved in 9 of 12 rabbits (75.0%) in group
      A, of which 4 rabbits survived longer than 3 months free of disease and another 5
      rabbits were found free of viable tumor when sacrificed. One rabbit was subjected
      to incomplete tumor ablation and two rabbits suffered from local tumor relapse
      and/or lung metastasis. The 3-month survival rate of RFA-treated rabbits was
      significantly higher (P < 0.01) than that of control rabbits. The typical MRI
      appearances of the acute RFA lesion consisted of five characteristic concentric
      zones, which corresponded to central needle track (zone A), tumor coagulation
      (zone B), pulmonary parenchyma coagulation (zone C), peripheral hemorrhage (zone
      D), and inflammatory layer (zone E) on histology. CONCLUSIONS: Eradication of
      pulmonary tumor could be achieved with current RFA technique in rabbits. MRI is a
      useful modality for assessment of lung tumor ablation.

PMID- 11469898
TI  - Strength over time of a resorbable bioscaffold for body wall repair in a dog
      model.
AB  - The change in strength over time of a biomaterial derived from the small
      intestinal submucosa (SIS) was determined in a dog model of body wall repair.
      Full-thickness body wall defects measuring 8 x 12 cm were surgically created and
      then repaired with a multilaminate eight-layer form of SIS in 40 dogs. Five dogs
      were sacrificed at each of the following time points: 1 day, 4 days, 7 days, 10
      days, and 1, 3, 6, and 24 months. Ball burst tests that measured biaxial ultimate
      load-bearing capability were performed on the device prior to implantation and on
      the device/implant site at the time of sacrifice. The strength of the device at
      the time of implant was approximately 73 +/- 12 pounds. The strength of the
      implant site diminished to 40 +/- 18 pounds at 10 days, and then progressively
      increased to a value of 156 +/- 26 pounds at 24 months (P < 0.05). The clinical
      utility of a degradable biomaterial such as SIS depends on a balance between the
      rate of degradation and the rate of host remodeling. Naturally occurring
      extracellular matrix scaffolds such as SIS show rapid degradation with associated
      and subsequent remodeling to a tissue with strength that exceeds that of the
      native tissue when used as a body wall repair device.

PMID- 11469897
TI  - Influence of humoral immunoreaction on hepatic nonparenchymal cells in ex situ
      xenoperfused rat livers.
AB  - BACKGROUND: The influence of xenogeneic humoral immunoreaction on hepatic
      nonparenchymal cells (NPCs) was evaluated ex situ in xenoperfused rat livers.
      METHODS: Isolated rat livers were perfused via the portal vein (PV) for 240 min.
      The perfusates consisted of fresh rat blood (group 1), fresh human blood (group
      2), and fresh human blood containing 5 microg/mL soluble complement receptor type
      1 (Group 3). RESULTS: Deposition of human IgM and C(5b-9) complement was observed
      in group 2, although only human IgM deposition was detected in group 3. Portal
      vein pressure in group 2 rose drastically during the first 10 min. Creatine
      kinase BB component gradually increased in all groups, followed by an elevation
      in alanine aminotransferase and both parameters were significantly higher in
      group 2 than in groups 1 and 3. In group 2, platelet thrombi in the peripheral
      PVs and periportal hemorrhage were observed after 10 min, and massive necrosis
      around the central veins after 240 min; these changes were not observed in group
      1 or 3. Production of tumor necrosis factor alpha and alpha interferon and
      expression of intercellular adhesion molecule 1 (ICAM-1) were lower in group 2
      than in groups 1 and 3. In group 2, there were negative areas for ICAM-1 and
      tumor necrosis factor alpha staining around the central veins after 240 min,
      which were consistent with necrotic areas. CONCLUSIONS: In xenoperfused rat
      livers, humoral mediators initially caused the disturbance of microcirculation,
      which would induce long ischemia in the pericentral areas, resulting in massive
      necrosis. NPC necrosis may be responsible for less production of cytokines and
      adhesion molecules in the xenoperfused livers.

PMID- 11469899
TI  - A novel model of ischemia in renal tubular cells which closely parallels in vivo
      injury.
AB  - PURPOSE: Renal ischemia-reperfusion (IR) injury is a devastating clinical
      problem. While effective animal models have been developed to investigate this
      condition, they are limited by differential renal cell inflammatory mediator
      production and heterogeneous cell sensitivity to ischemia. We therefore developed
      an in vitro model of renal tubular cell ischemia that simulates the cellular
      injury observed in animal models of renal IR injury. MATERIALS AND METHODS: Using
      the established renal tubular cell line, LLC-PK1, simulated ischemia was induced
      by immersing the cellular monolayer in mineral oil. The effect of simulated
      ischemia on renal tubular cells was then determined by measuring the time course
      of TNF-alpha protein expression (ELISA), TNF-alpha mRNA induction (RT-PCR), and
      renal tubular cell apoptosis (TUNEL). RESULTS: Maximal TNF-alpha protein
      expression occurs following 60 min of simulated ischemia and 2 h of substrate
      replacement (reimmersion in media), and maximal TNF-alpha mRNA induction occurs
      following 60 min of simulated ischemia. Cellular apoptosis peaks following 60 min
      of simulated ischemia and 24 h of reperfusion. CONCLUSION: The time course of TNF
      alpha production and apoptosis induction in this model closely parallels the time
      course for these markers in vivo. This study constitutes the initial
      demonstration that an in vitro oil immersion model of ischemia simulates the
      cellular injury (TNF-alpha production and apoptosis) observed in animal models of
      renal ischemia-reperfusion. This model may be used to study cellular mechanisms
      of IR in the absence of the systemic confounding variables.

PMID- 11469900
TI  - Expression of peptide transporter following intestinal transplantation in the
      rat.
AB  - BACKGROUND: The absorptive function of the intestinal graft is one of the most
      important factors for successful intestinal transplantation. To clarify whether
      the intestinal H(+)/peptide cotransporter (PEPT1) was expressed in the
      transplanted intestine, we examined the expression of PEPT1 in an experimental
      model of rat small intestinal transplantation in comparison with expression of
      Na(+)/glucose cotransporter (SGLT1). MATERIALS AND METHODS: Heterotopic
      intestinal transplantation was performed in allogeneic and syngeneic rat strain
      combinations. An additional group of allogeneic recipients was treated with
      tacrolimus (1 mg/kg) prior to transplantation, then daily for 7 days. Intestinal
      grafts were examined for histopathology and PEPT1 and SGLT1 expression. RESULTS:
      In the isografts, the levels of messenger RNA (mRNA) encoding both transporters
      were not changed, while the amount of SGLT1 protein was decreased and that of
      PEPT1 protein was increased. In the allografts, mRNA level and protein amount of
      both transporters and the amount of villin protein were decreased, and
      microscopic examination revealed histopathological features of rejection on day
      7. Tacrolimus treatment ameliorated the histopathological features and prevented
      the decrease in villin protein expression. However, the decreases in PEPT1 and
      SGLT1 expression (both mRNA and protein) were partially prevented by tacrolimus
      treatment. CONCLUSION: This study indicated that the expression of transporters
      should be determined to evaluate intestinal graft function in addition to
      histopathological examination of the mucosa and that the levels of mRNA encoding
      intestinal nutrient transporters in biopsy specimens may be useful for evaluating
      the intestinal graft function for intestinal transplant patients.

PMID- 11469901
TI  - Increased c-myb mRNA expression in Barrett's esophagus and Barrett's-associated
      adenocarcinoma.
AB  - BACKGROUND: Esophageal adenocarcinoma develops through a multistage process which
      is characterized histopathologically by progression from Barrett's intestinal
      metaplasia to Barrett's esophagus with dysplasia and ultimately to
      adenocarcinoma. The genetic basis of this process is increasingly well
      understood, but no studies have examined the role of the transcription factor c
      myb in this disease. MATERIALS AND METHODS: c-myb mRNA expression levels were
      measured using a quantitative reverse transcription-polymerase chain reaction (RT
      PCR) method in specimens of Barrett's intestinal metaplasia (n = 16),
      adenocarcinoma (n = 22), matching normal squamous esophagus tissues (n = 38), and
      normal squamous esophagus tissues from patients without Barrett's esophagus or
      chronic gastroesophageal reflux disease (n = 10). RESULTS: The median c-myb mRNA
      expression levels were significantly increased in Barrett's intestinal metaplasia
      tissues compared to normal esophagus tissues (P = 0.013) and in Barrett's
      associated adenocarcinoma tissues compared to normal squamous esophagus tissues
      (P = 0.001). The c-myb expression levels increased progressively and
      significantly in histopathologically worse tissue types, with an increase from
      normal squamous esophagus mucosa to Barrett's intestinal metaplasia, and from
      Barrett's intestinal metaplasia to adenocarcinoma of the esophagus (P = 0.002).
      Median c-myb expression levels were also significantly higher in histologically
      normal squamous esophagus tissues from cancer patients compared to normal
      esophagus tissues from patients without cancer (P < 0.001) and a control group
      without evidence of Barrett's esophagus or gastroesophageal reflux disease (P =
      0.003). Very high c-myb mRNA expression levels were found only in patients with
      cancer. CONCLUSION: These findings suggest that upregulation of c-myb mRNA
      expression is an early event in the development of Barrett's esophagus and
      associated adenocarcinoma, that high c-myb mRNA expression levels may be a
      clinically useful biomarker for the detection of occult adenocarcinoma, and that
      a widespread cancer "field" effect is present in the esophagus of patients with
      Barrett's-associated adenocarcinoma.

PMID- 11469902
TI  - Cytosolic phospholipase A(2)-mediated ICAM-1 expression is calcium dependent.
AB  - BACKGROUND: Some human malignancies such as virus-related hepatocellular cancer
      arise in a setting of chronic inflammation. Upregulation of ICAM-1 is a seminal
      late event in malignant transformation following chronic inflammation. Cytosolic
      phospholipase A(2) (cPLA(2)) is a lipid-mediator activated by inflammatory
      stimuli, which has been shown to mediate ICAM-1 upregulation. As lipid mediators
      are known to work via calcium-dependent mechanisms in nearly all mammalian cells,
      we hypothesize that inflammatory-mediated ICAM-1 upregulation is dependent on
      both cPLA(2) and intracellular calcium. MATERIALS AND METHODS: HUVEC were chosen
      as a representative cell line as they emulate hepatic sinusoids and are a well
      established cell model. These were grown to confluence in T-25 flasks and
      stimulated with TNF-alpha or LPS for 6 h. Additional groups were preincubated
      with AACOCF3 (a specific cPLA(2) inhibitor) or BAPTA A.M. (a specific inhibitor
      of intracellular Ca(2+)) prior to being exposed to inflammatory stimuli. ICAM-1
      expression was determined by mean fluorescent intensity (MFI) as measured by FITC
      labeled moAb to ICAM-1 via FACS. The role of intracellular Ca(2+) on cPLA(2)
      activity was determined by thin-layer chromatography. Groups were compared using
      ANOVA with Scheffe's post hoc analysis; *P < 0.05 vs control, daggerP < 0.05 vs
      LPS and TNF-alpha was considered significant; N > or = 4 all experimental groups.
      RESULTS: Both cPLA(2) and Ca(2+) inhibition significantly inhibited inflammatory
      upregulation of ICAM-1. Pretreatment with BAPTA A.M. attenuated HUVEC cPLA(2)
      activity in response to LPS. These findings suggest that appropriate molecular
      target suppression may prevent malignant degeneration in the presence of chronic
      inflammation.

PMID- 11469903
TI  - Inosine attenuates tourniquet-induced skeletal muscle reperfusion injury.
AB  - BACKGROUND: Adenosine attenuates skeletal muscle reperfusion injury, but its
      short half-life in vivo limits potential therapeutic benefits. The aim of this
      study was to ascertain whether inosine, a stable adenosine metabolite, modulates
      skeletal muscle reperfusion injury. MATERIALS AND METHODS: C57BL/6 mice were
      randomized (8-10 per group) to six groups: time controls; inosine (100 mg/kg)
      before anesthesia; 2 h of bilateral tourniquet hindlimb ischemia; I/R (2 h of
      bilateral tourniquet hindlimb ischemia, 3 h of reperfusion); inosine (100 mg/kg)
      before I/R; drug vehicle before I/R. Serum tumor necrosis factor (TNF)-alpha and
      macrophage inflammatory protein (MIP)-2 were measured before ischemia and at the
      end of reperfusion. Tissue edema was determined by wet/dry weight ratios. Tissue
      leucosequestration was assessed by the myeloperoxidase (MPO) content. RESULTS: At
      the end of reperfusion, inosine pretreatment resulted in lower MPO levels in
      muscle (P = 0.02) and lung (P = 0.0002) than saline pretreatment. Similarly,
      muscle (P = 0.04) and lung (P = 0.02) wet/dry ratios were significantly reduced
      with inosine but not with saline pretreatment. At the end of reperfusion, serum
      proinflammatory cytokine levels (TNF-alpha and MIP-2) were significantly reduced
      (P < 0.05) compared to preischemia levels following inosine pretreatment but not
      saline pretreatment. Ischemia alone did not alter any of the parameters assessed.
      CONCLUSIONS: These findings demonstrate that pretreatment with inosine attenuates
      the local and systemic proinflammatory responses associated with skeletal muscle
      reperfusion injury.

PMID- 11469904
TI  - Prophylaxis against Staphylococcus aureus vascular graft infection with mupirocin
      soaked, collagen-sealed dacron.
AB  - A rat model was used to investigate the efficacy of mupirocin in the prevention
      of vascular prosthetic graft infections. The effect of mupirocin-soaked Dacron
      was compared with the effect of rifampin-soaked, collagen-sealed Dacron in the
      rat model of graft infection caused by methicillin-susceptible Staphylococcus
      aureus and methicillin-resistant S. aureus. Graft infections were established in
      the back subcutaneous tissue of 195 adult male Wistar rats by implantation of 1
      cm(2) Dacron prostheses followed by topical inoculation with 5 x 10(7) colony
      forming units of S. aureus. The study included a control group (no graft
      contamination), two contaminated groups that did not receive any antibiotic
      prophylaxis, two contaminated groups in which perioperative intraperitoneal
      amoxicillin clavulanate prophylaxis (50 mg/kg) was administered, four
      contaminated groups that received mupirocin- or rifampin-soaked graft, and four
      contaminated groups that received mupirocin- or rifampin-soaked graft and
      perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg). The
      grafts were sterilely removed 7 days after implantation and the infection was
      evaluated by using sonication and quantitative agar culture. Data analysis showed
      that the efficacy of mupirocin against both strains was significantly different
      from that of the untreated control. In addition, mupirocin was more effective
      than rifampin against the methicillin-resistant strain. Finally, only the
      combination of mupirocin and amoxicillin clavulanate produced complete
      suppression of growth of all strains.

PMID- 11469905
TI  - Shed L-selectin (sCD62L) load in trauma patients.
AB  - BACKGROUND: Low circulating plasma concentrations of the leukocyte adhesion
      molecule L-selectin (sCD62L) were found to be associated with an increased risk
      for subsequent lung failure and case fatality after severe trauma. The objective
      of this study was to determine the robustness of soluble L-selectin, correcting
      for a broad spectrum of physiological variables. METHODS: Patients with suspected
      multiple and/or trunk injuries were enrolled into this study over a 1-year
      period. Plasma samples were obtained on hospital presentation, and circulating
      soluble L-selectin was measured with a commercially available ELISA kit. Study
      records comprised all relevant clinical and laboratory data. Thirty-day survival
      rate, subsequent acute lung failure, and nosocomial pneumonia were defined as
      study endpoints. Statistical analysis was performed using multivariate logistic
      regression models. RESULTS: Seventy patients with a mean age of 35.51 years
      (range, 10-87 years) and a mean ISS score of 36.61 (95% CI, 31.08-42.14) entered
      the study. Eleven patients died, leading to an attributable mortality of 15.70%.
      L-Selectin levels did not differ between survivors and nonsurvivors. Five
      patients progressed to acute lung injury, whereas 11 patients developed hospital
      acquired pneumonia. Lower L-selectin levels indicated patients at risk for lung
      injury with a relative odds estimated at 4.43 (P = 0.017). Statistical
      significance diminished in the multivariate model. In contrast, plasma
      concentrations of circulating sCD62L were significantly decreased in patients
      developing nosocomial pneumonia (P = 0.023), with a twofold increased relative
      odds (OR, 1.96; 95% CI, 0.51-7.50). No effect modification was observed by the
      included covariables. CONCLUSIONS: The results of this study highlight the
      independent predictive value of initially decreased soluble L-selectin levels for
      the identification of patients susceptible to subsequent respiratory
      complications after severe trauma.

PMID- 11469906
TI  - Preconditioning somatothermal stimulation on right seventh intercostal nerve
      territory increases hepatic heat shock protein 70 and protects the liver from
      ischemia-reperfusion injury in rats.
AB  - Hyperthermic preconditioning attenuates the heat-induced cellular response to a
      subsequent severe heat challenge. However, it is impractical to perform whole
      body hyperthermia in humans. This study was designed to test the hypotheses that
      hepatic heat shock protein 70 (Hsp70) could be induced by local somatothermal
      stimulation (LSTS) on right seventh intercostal nerve territory and that
      preconditioning the rats with LSTS protects the liver from subsequent ischemia
      reperfusion injury. LSTS was brought about by application of a heating rod above
      right seventh intercostal nerve territory in male Sprague-Dawley rats. Hepatic
      gene expression of Hsp70 was assessed by Western blot and reverse transcription
      polymerase chain reaction (RT-PCR). Finally, serum ALT and AST and the lipid
      peroxidation product malondialdehyde (MDA) were evaluated in ischemic-reperfused
      rats preconditioned by application of LSTS on right seventh intercostal nerve
      territory. The results showed that hepatic gene expression of Hsp70 was
      upregulated in rats treated with LSTS. When animals were preconditioned with
      LSTS, followed by subsequent ischemia-reperfusion injury of the liver, there were
      significant decreases in liver enzymes (ALT/AST) and MDA formation in rats
      pretreated with one dose of LSTS (LSTS-1 group) as compared with those not
      treated with LSTS (control group) or treated with three doses of LSTS (LSTS-3
      group). We conclude that mild local heat stress (one dose) on right seventh
      intercostal nerve territory upregulates hepatic gene expression of Hsp70 and
      protects the liver from subsequent ischemia-reperfusion injury. This might
      provide an easily applicable method for those patients facing ischemia
      reperfusion challenge of the liver, as in liver resection and liver
      transplantation.

PMID- 11469907
TI  - Visual validation of the mechanical stabilizing effects of positive end
      expiratory pressure at the alveolar level.
AB  - BACKGROUND: Positive end-expiratory pressure (PEEP) reduces ventilator-induced
      lung injury (VILI), presumably by mechanically stabilizing alveoli and decreasing
      intrapulmonary shear. Although there is indirect support for this concept in the
      literature, direct evidence is lacking. In a surfactant depletion model of acute
      lung injury we observed unstable alveolar mechanics referred to as repeated
      alveolar collapse and expansion (RACE) as measured by changes in alveolar area
      from inspiration to expiration (I - E(Delta)). We tested the hypothesis that over
      a range of tidal volumes PEEP would prevent RACE by mechanically stabilizing
      alveoli. MATERIALS AND METHODS: Yorkshire pigs were randomized to three groups:
      control (n = 4), Tween (surfactant-deactivating detergent) (n = 4), and Tween +
      PEEP (7 cm H(2)O) (n = 4). Using in vivo video microscopy individual alveolar
      areas were measured with computer image analysis at end inspiration and
      expiration over consecutive increases in tidal volume (7, 10, 15, 20, and 30
      cc/kg.) I - E(Delta) was calculated for each alveolus. RESULTS: Surfactant
      deactivation significantly increased I - E(Delta) at every tidal volume compared
      to controls (P < 0.05). PEEP prevented this change, returning I - E(Delta) to
      control levels over a spectrum of tidal volumes. CONCLUSIONS: RACE occurs in our
      surfactant deactivation model of acute lung injury. PEEP mechanically stabilizes
      alveoli and prevents RACE over a range of tidal volumes. This is the first study
      to visually document the existence of RACE and the mechanical stabilizing effects
      of PEEP at the alveolar level. The ability of PEEP to stabilize alveoli and
      reduce shear during mechanical ventilation has important implications for
      therapeutic strategies directed at VILI and acute respiratory distress syndrome.

PMID- 11469908
TI  - v-Src transformation is mediated through farnesylated proteins.
AB  - Src is an oncoprotein which has been implicated in a number of human malignancies
      in which it has been shown to be overexpressed and highly activated. The precise
      mechanism of Src transformation, however, is still poorly understood. We
      hypothesized that Ras and other farnesylated proteins may mediate Src
      transformation. To test this hypothesis, v-Src-transfected rat fibroblasts (3Y1)
      were treated every 72 h with a 15 microM concentration of a farnesyl-transferase
      inhibitor (FTI). At 2 weeks, a focus formation assay was performed to assess
      transformation potential. Untreated and FTI-treated v-Src-transfected 3Y1 cells
      formed a mean of 39 (+/-2.6) and 29.8 (+/-2.9) foci per well, respectively. This
      24% decrease was judged to be statistically significant (P = 0.02). Moreover,
      foci (>90%) in the FTI-treated wells were also consistently smaller than foci in
      the untreated wells. Western blots with antibody directed toward H-Ras confirmed
      complete inhibition of Ras farnesylation in the treated cell lines. The
      specificity of this inhibition was verified by Western blot using antibody
      specific for Rap1A. The transforming potential of v-Src is inhibited, but not
      eliminated by FTI treatment. This suggests that v-Src transformation is mediated
      in part by farnesylated proteins, one of which may be Ras.

PMID- 11469909
TI  - Effect of hypoxia on fetal rabbit gastrointestinal motility.
AB  - During fetal hypoxic stress, blood flow is shunted from nonvital to life
      preserving organs, including the heart and brain. Reduced oxygen to the small
      intestine (SI) induces mucosal injury and may contribute to neonatal necrotizing
      enterocolitis (NEC). As little is known about the relationship between fetal
      hypoxia and GI motility, we assessed potential effects in a rabbit model. Twenty
      one pregnant rabbits were randomized into two groups, hypoxia (Hyp) and control
      (Cont). Seven litters were studied at Gestational Days 24, 27, and 30 of their
      normal 31-day gestation. Under ultrasound guidance each fetal stomach was
      percutaneously accessed. Fluorescein, labeled with color-coded microspheres for
      precise fetal identification, was injected. Hyp rabbits breathed 11% oxygen for 1
      h after recovery from anesthesia; Cont rabbits breathed room air. Two hours after
      injection, fetuses were delivered and weighed. The SI was harvested, the length
      recorded, and the distance fluorescein traveled measured by UV light optical
      density. Results were analyzed by the unpaired Student test. All injected fetuses
      (N = 167) survived. The length fluorescein traveled was shorter in Hyp than Cont
      at all gestational days studied (P < 0.01): Day 24, Hyp = 6.7 +/- 2.0 vs Cont =
      8.4 +/- 2.1 cm; Day 27, Hyp = 10.1 +/- 2.9 vs Cont = 19.1 +/- 4.4 cm; and Day 30,
      Hyp = 16.8 +/- 3.5 vs Cont = 23.1 +/- 5.2 cm. The percentage motility, defined as
      the length of fluorescein travel divided by total SI length, was also
      significantly less at all gestational days. Fetal rabbit GI motility was
      significantly decreased by maternal hypoxia during the last third of gestation.
      Hypoxia-induced reduction in GI motility may contribute to neonatal NEC.

PMID- 11469910
TI  - Small bowel tissue engineering using small intestinal submucosa as a scaffold.
AB  - BACKGROUND: Small intestinal submucosa (SIS) is an extracellular matrix used in
      tissue engineering studies to create de novo abdominal wall, urinary bladder,
      tendons, blood vessels, and dura mater. The purpose of this study is to evaluate
      the feasibility of using SIS as a scaffold for small bowel regeneration in an in
      situ xenograft model. MATERIALS AND METHODS: Twenty-three dogs had a partial
      defect created on the small bowel wall which was repaired with a SIS patch. Four
      dogs underwent small bowel resection with placement of an interposed tube of SIS.
      The animals were followed 2 weeks to 1 year. RESULTS: Three of the 23 dogs with
      SIS placed as a patch died shortly after surgery due to leakage from the site.
      The other 20 dogs survived up to time of elective necropsy with no evidence of
      intestinal dysfunction. At necropsy, the bowel circumference in the patched area
      had no stenosis. Histological evaluation showed the presence of a mucosal
      epithelial layer, varying amount of smooth muscle, sheets of collagen, and a
      serosal covering. Architecturally, the layers were not well organized in the
      submucosal region. An abundance of inflammatory cells was present in the early
      postoperative period but receded with time. All 4 dogs with a tubular segment of
      SIS interposed had significant problems. One had partial obstruction at 1 month,
      and 3 died in the early postoperative period due to leakage. CONCLUSIONS: This
      preliminary study suggests that SIS patches can be used for small bowel
      regeneration. Tubular segmental replacement is not feasible at this time.

PMID- 11469911
TI  - Systemic effects of acute terminal ileitis on uninflamed gut aggravate bile acid
      malabsorption.
AB  - BACKGROUND: Some patients with terminal ileitis suffer from significant bile acid
      malabsorption even if the inflammation is locally limited. We hypothesized that
      inflammation in the terminal ileum may lead to changes in mucosal absorption in
      more proximal intestinal segments and aggravate bile acid malabsorption. METHODS:
      Five hamsters underwent laparotomy and localized instillation of 2,4,6
      trinitrobenzenesulfonic acid (TNBS) in 10% ethanol into the last 4 cm of ileum to
      create terminal ileitis. A control group (n = 5) underwent instillation of
      saline. Animals were sacrificed after 24 h. Active and passive transport of
      radiolabeled bile acids was measured in the proximal and terminal ileum and
      glucose absorption in the jejunum using an everted sleeve technique.
      Myeloperoxidase (MPO) activity and histomorphology were examined by standard
      methods. RESULTS: In animals with ileitis, active bile acid uptake decreased by
      84% in the terminal ileum (t test, P <0.001) and by 58% in the proximal ileum (P
      < 0.05) compared with saline-treated controls. Jejunal glucose absorption
      decreased by 59% (P < 0.01). Passive bile acid and glucose absorption rates were
      not significantly changed in any segments of treated animals versus controls.
      Histological examination of the treated group revealed signs of acute terminal
      ileitis without changes in the proximal ileum and jejunum. All control tissues
      were uninflamed. MPO activity was 13-fold increased in the inflamed ileal samples
      compared with controls (P <0.001). No significant changes were seen in the
      proximal ileum and jejunum. There was no evidence of reflux of TNBS into proximal
      ileum. Nominal mucosal surface area values showed no significant changes between
      groups. Pretreatment of an additional group of hamsters (n = 5) with
      acetylsalicylic acid before TNBS instillation ameliorated the inflammatory
      response in the terminal ileum and largely abrogated the negative effects on
      ileal bile acid absorption. CONCLUSION: These data suggest that limited acute
      ileitis impairs active bile acid uptake in the terminal ileum. It also diminishes
      active bile acid and glucose absorption in more proximal segments of the small
      intestine, likely by a systemic effect. This systemic effect may aggravate bile
      acid malabsorption in patients with limited ileitis.

PMID- 11469912
TI  - Platelet activating factor antagonism reduces the systemic inflammatory response
      in a murine model of acute pancreatitis.
AB  - BACKGROUND: The platelet activating factor (PAF) antagonist, Lexipafant, has been
      used in experimental models and clinical trials to treat severe acute
      pancreatitis (AP). The purpose of this study was to determine whether Lexipafant
      reduces the local and systemic components of AP in a murine model of mild,
      edematous AP. MATERIALS AND METHODS: Forty-eight female Swiss-Webster mice were
      divided into four groups. Group 1 received 50 microl of saline ip every hour for
      6 h (sham). Group 2 received saline treatment, plus Lexipafant (25 mg/kg dose ip,
      every 3 h starting 1 h after the first saline injection) (sham/Lex). Group 3
      received cerulein (50 microg/kg dose ip, every hour for 6 h) (AP). Group 4
      received AP, plus therapeutic treatment with Lexipafant (AP/Lex). Animals were
      sacrificed 3 h after the last injection. Serum cytokine levels were determined by
      ELISA. Standard assays were performed for serum amylase activity and lung
      myeloperoxidase activity (MPO). Histology was scored by two blinded
      investigators. RESULTS: Serum cytokines (TNFalpha, IL-1beta), lung MPO, and serum
      amylase activity were reduced by PAF antagonism. Histology showed a trend toward
      improvement with Lexipafant, but did not reach statistical significance.
      CONCLUSION: The PAF antagonism reduces the severity of systemic inflammation when
      given after the induction of mild AP in mice. These results suggest that
      Lexipafant may be useful in the treatment of mild pancreatitis after its clinical
      onset.

PMID- 11469913
TI  - Murine aortic aneurysm produced by periarterial application of calcium chloride.
AB  - A murine abdominal aortic aneurysm model was developed by applying calcium
      chloride periarterially. A 13.6 mEq/10 ml calcium chloride solution was applied
      to the abdominal aorta of nine mice. Three mice were randomly selected at the end
      of the first, second, and third weeks postoperatively, and their vessel diameters
      were measured. The vessel diameter at the end of the first week postoperatively
      was 0.39 +/- 0.03 mm (mean +/- SD) pretreatment and 0.41 +/- 0.03 mm
      posttreatment (5.3% increase, P > 0.05). The vessel diameter at the end of the
      second week postoperatively was 0.48 +/- 0.03 mm pretreatment and 0.78 +/- 0.20
      mm posttreatment (64% increase, P < 0.05). The vessel diameter at the end of the
      third week postoperatively was 0.57 +/- 0.14 mm pretreatment and 1.16 +/- 0.43 mm
      posttreatment (110% increase, P < 0.05). Nine other murine abdominal aortas were
      treated with sodium chloride, and their vessel diameters were measured in similar
      7-day intervals. No measurements in this group were statistically significant
      when comparing pretreatment to posttreatment vessel diameters. A larger number of
      inflammatory infiltrates was observed in the intima and media layers of calcium
      chloride-treated mice. Underlying mechanisms for this model include disrupting
      the elastic network within the media by calcium precipitations and activating the
      inflammatory response. We conclude that periarterial application of calcium
      chloride is a convenient and reliable model for creating abdominal aortic
      aneurysms in mice.

PMID- 11469914
TI  - Adenoviral mediated uteroglobin gene transfer to the adventitia reduces arterial
      intimal hyperplasia.
AB  - PURPOSE: The aim of this study was to investigate the feasibility of gene
      transfer of uteroglobin, a potent anti-inflammatory and immunomodulatory agent,
      via adenoviral mediated gene transfer to the adventitia in the mouse carotid
      ligation injury model and also to investigate the efficacy of uteroglobin in
      reducing neointimal hyperplasia. METHODS: Forty-five C57bl/6NHSD mice were
      anesthetized and left common carotid artery ligation was performed. Adenoviral
      vector encoding the uteroglobin gene (Ad.UG; 15 microl of 1.35 x 10(11) pfu/mL)
      was applied to the adventitia of the injured artery in 16 mice. In our control
      groups, 16 mice received adenoviral vector encoding the beta-galactosidase
      reporter gene (Ad.lacZ; 15 microl of 1.0 x 10(11) pfu/mL) and 13 mice received
      PBS only. Six mice from each group were sacrificed at 4 days for carotid artery
      protein extraction and Western blot analysis. The remainder were harvested at 30
      days for histologic and morphometric analysis. The intima/media area ratios were
      calculated for each artery. The results were analyzed and compared using ANOVA
      and Bonferroni/Dunn post hoc testing. RESULTS: Two mice from the LacZ group and
      one from the PBS group died before the 30-day endpoint. Uteroglobin expression
      was demonstrated in the Ad.UG treated arteries by Western blot analysis.
      Morphometric analysis demonstrated a statistically significant reduction in the
      intima/media area ratio of Ad.UG treated carotids compared to controls. There was
      a reduction of intima/media ratio with Ad. UG treatment of 68% compared to
      Ad.lacZ treatment (P < 0.0001) and 62% compared to PBS treatment (P = 0.0006).
      There was no statistical difference between the control groups. CONCLUSION:
      Adenoviral mediated gene transfer via the adventitia is an effective mode of gene
      delivery. Adventitial uteroglobin gene transfer using an adenoviral vector
      induces uteroglobin protein production and significantly reduces neointimal
      hyperplasia in the mouse carotid ligation injury model.

PMID- 11469915
TI  - Nicotine induces endothelial TNF-alpha expression, which mediates growth
      retardation in vitro.
AB  - PURPOSE: Atherosclerosis is understood as the common pathologic manifestation of
      arterial injury caused by a variety of etiologies. One well-established etiologic
      agent is nicotine. We hypothesized that cytokines of endothelial origin are
      involved with the pathologic changes found in atherosclerosis associated with
      smoking. We chose to assay for TNF-alpha due to its many biologic actions that
      are similar to those found in peripheral vascular disease. METHODS: Human
      umbilical vein endothelial cells (HUVEC) were plated in endothelial growth medium
      (EGM-2) on plastic coverslips until 75% confluent. Free base nicotine (FBN) was
      diluted in EGM-2 to a concentration of 10(-8) M and added to experimental cells.
      At 1, 3, and 24 h, coverslips were removed and fixed. Immunohistochemical
      staining was performed using anti-TNF-alpha. Digital image analysis (DIA) was
      performed to quantify expression of TNF-alpha. An intensity stain index measuring
      area and intensity of stain/total cellular area was determined for each time
      point (n = 5). Additional HUVEC were plated in 12-well plates in EGM-2 at 2 x
      10(3) cells/cm(2) on T(-2) day. FBN was diluted in medium to 10(-9) M and added
      to wells with and without 0.9 microg/ml anti-TNF-alpha on T(0) day. Cell counts
      were performed in triplicate on days T(2-5) utilizing hemocytometry. Data was
      analyzed using Student's t test and ANOVA, with a 95% confidence interval.
      RESULTS: Dose response determinations showed that the minimal concentration
      required to show statistically significant cell retardation is 10 (-9) M.
      Accordingly, this concentration was used for subsequent proliferation studies.
      DIA showed a threefold increase in TNF-alpha activity at 1 h and a twofold
      increase at 3 h. Activity returned to baseline by 24 h. Cell growth was
      significantly decreased in cells exposed to nicotine when compared to controls on
      days T(2)-T(5) (P < 0.05). In cells exposed to anti-TNF-alpha and nicotine there
      was inhibition of the growth retardation seen in the cells containing nicotine
      alone. Differences between the control group and the anti-TNF-alpha group were
      not statistically significant. CONCLUSION: These data demonstrate the ability of
      endothelial cells to secrete TNF-alpha in response to nicotine at levels found in
      serum after smoking and also shows that endothelial cell growth retardation as a
      consequence of nicotine exposure may be TNF-alpha mediated.

PMID- 11469916
TI  - Regulation of c-met expression in rats with acute hepatic failure.
AB  - BACKGROUND: Earlier we described a model of fulminant hepatic failure (FHF) in
      the rat where partial hepatectomy is combined with induction of right liver lobe
      necrosis. In FHF rats, lack of hepatocyte proliferation was associated with
      delayed expression of HGF and HGF receptor c-met. Since the c-met promoter region
      has Sp1 binding sites, we decided to examine whether in FHF rats down-regulation
      of c-met is associated with decreased Sp1 function and whether changes in blood
      HGF, IL-6, and TGFbeta1 levels might be responsible for these effects. MATERIALS
      AND METHODS: Induction of FHF, partial (2/3) hepatectomy (PH), and sham
      hepatectomy (SH) was performed in adult Sprague-Dawley rats. The levels of c-met
      mRNA and Sp1 DNA binding activity were studied in rat liver remnants at different
      time points after surgery. Blood levels of HGF, IL-6, and TGFbeta1 were also
      measured in these rats. Additionally, the effects of treatment with TGF-beta1, IL
      6, or a combination of both on c-met expression and Sp1 DNA binding were studied
      in HGF-induced rat hepatocyte cultures. RESULTS: Compared to SH rats, in PH rat
      livers c-met was up-regulated after 6 h and Sp1 DNA binding was at or only
      slightly lower than levels at all time points studied. In FHF rat livers, c-met
      expression was markedly reduced after 2 and 6 h, moderate after 12 h, and
      undetectable after 24 h. At the same time, Sp1 DNA binding was detected at 2 h
      postinduction only. In FHF rats, blood levels of all three cytokines showed early
      and sustained elevation. In vitro, IL-6 had no effect on c-met expression,
      whereas TGFbeta1 up-regulated c-met. When used alone, none of the cytokines
      affected Sp1 DNA binding activity. In contrast, a combination of IL-6 and
      TGFbeta1 down-regulated c-met expression as well as Sp1 DNA binding activity.
      These effects were dependent on the IL-6 concentration used. This study suggests
      that following massive loss of hepatocyte mass in rats, early increase in blood
      IL-6 and TGFbeta1 levels may weaken the expression of HGF receptor c-met in
      surviving hepatocytes through suppression of Sp1 DNA binding.

PMID- 11469917
TI  - The effect of instrumental and vocal music on adherence to a physical
      rehabilitation exercise program with persons who are elderly.
AB  - This study compared live, instrumental music, vocal music, and no music on the
      repetition frequencies for 14 prescribed physical therapy rehabilitation
      exercises. Male (N = 4) and female (N = 15) residents of care centers for older
      adults served as subjects. They ranged in age from 65 to 90 years (M= 84.3), and
      were either referred to physical therapy or were already involved in a physical
      therapy exercise pro-gram. All subjects (N = 19) participated in 6 treatment
      sessions under 3 conditions: Two sessions with live instrumental music, two with
      live vocal music, and two with no music. In all music sessions, familiar and
      recognizable songs were paired with specific exercises. Each exercise in all
      conditions had the same duration, and a metronome established consistent tempos.
      Each session was videotaped for later review and data collection. Analyses of
      variance were calculated for treatment effects and mean differences among the
      three conditions which yielded significant treatment effects and treatment
      differences among conditions for 6 of the 14 exercises. Unsolicited comments from
      subjects indicated preference for music over no music conditions while
      exercising. Further study is required to establish the relationship between music
      enhanced exercises and adherence to exercise regimens in populations of older
      adults.

PMID- 11469918
TI  - Therapeutic instrumental music playing in hand rehabilitation for older adults
      with osteoarthritis: four case studies.
AB  - The purpose of this study was to examine the effects of keyboard playing on the
      management of hand osteoarthritis in older adults. Four participants, with
      diagnoses of hand osteoarthritis, met the investigator 4 days a week, for
      approximately 30 minutes, for 4 weeks. Participants played folk and big band
      melodies on a Yamaha PSR-510 touch-sensitive electronic keyboard for 20 minutes
      each session. Evaluation included pre and poststudy occupational therapy measures
      of finger pinch meter, and range of motion. Participants assessed arthritic
      discomfort using a visual Likert scale (1-10) before and after each session. A
      MIDI sequencing computer program, Master Tracks Pro, measured finger velocity,
      before and after each session. Results indicated that finger pinch meter and
      range of motion were positively increased by keyboard playing. Two participants
      recorded significant decreases in arthritic discomfort after playing, while three
      participants showed significant improvement in finger velocity and hence, finger
      strength/dexterity due to treatment. Participants enjoyed the treatment with
      enjoyment ratings of 3 or higher on a 5-point Likert scale. Additional benefits
      included improved structure of leisure time and increased socialization for older
      adults with osteoarthritis who tend to isolate themselves due to disease
      deterioration.

PMID- 11469919
TI  - The use of music on Barney & Friends: implications for music therapy practice and
      research.
AB  - This descriptive study examined the music content of 88 episodes from the PBS
      television show Barney & Friends, which aired from September 1992 to September
      1998, in an attempt to quantify musical examples and presentations that may be
      considered introductory music experiences for preschoolers. Using many of the
      procedures identified by Wolfe and Stambaugh (1993) in their study on the music
      of Sesame Street, 25% of Barney & Friends' 88 episodes were analyzed by using the
      computer observation program SCRIBE in determining: (a) the temporal use of
      music; (b) performance medium; and (c) intention of music use. Furthermore, each
      structural prompt presentation (n = 749) from all 88 episodes was examined for:
      (a) tempo; (b) vocal range; (c) music style; (d) word clarity; (e) repetition;
      (f) vocal modeling; and (g) movement. Results revealed that the show contained
      more music (92.2%) than nonmusic (7.8%), with the majority of this music
      containing instrumental sounds (61%). The function of this music was distributed
      equally between structural prompt music (48%) and background music (48%). The
      majority of the structural prompt music contained newly composed material (52%),
      while 33% consisted of previously composed material. Fifteen percent contained a
      combination of newly composed and previously composed material. The most common
      tempo range for presentations on the show was 80-100 bpm, while vocal ranges of a
      9th, 8th, 6th, and 7th were predominant and most often sung by children's voices.
      The adult male voice was also common, with 84% of all adult vocals being male.
      The tessitura category with the greatest number of appearances was middle C to C
      above (n = 133), with the majority of the presentations (n = 435, 73%) extending
      singers' voices over the register lift of B above middle C. Children's music and
      music of the American heritage were the most common style categories observed,
      and these two categories combined on 260 (35%) presentations. The use of
      choreographed movement and props/costumes was also prevalent, and may have
      contributed to high interobserver reliability of tempo. Implications for music
      therapists and teachers working with young children and music researchers
      examining various epistemological questions of music learning and behavior are
      discussed.

PMID- 11469920
TI  - Participation of a preschooler with visual impairments on the playground: effects
      of musical adaptations and staff development.
AB  - The purpose of this study was to evaluate the adaptations of a playground, and
      subsequently staff development, on the participation of a 3-year-old boy with
      congenital blindness. A single-subject design with three conditions (baseline,
      adaptations of the playground, and staff development) was used. The playground
      adaptation involved adding musical stations in strategic locations on the
      playground and connecting them with a "path" that provided auditory feedback. The
      staff training involved the music therapist providing individualized instruction
      to the staff who supervised the child. The child's participation was measured in
      terms of social interaction with peers or adults, play and engagement with
      materials, movement on the playground, and stereotypic behaviors. The playground
      adaptation resulted in no changes in the child's social interactions with peers
      or adults, increases in engagement, no change in movement on the playground, and
      a decrease in stereotypic responses. Staff training resulted in increased but
      variable interactions with adults and peers, in additional increases in
      engagement, less movement, and similar levels of stereotypic behavior. The
      findings suggest that musical adaptations of physical environments may he helpful
      but not sufficient for promoting desired outcomes.

PMID- 11469921
TI  - Issues in complementary therapies: how we got to where we are.
AB  - Consumer interest in and use of complementary/alternative therapies has increased
      exponentially in the past decades. Although many of the over 1800 therapies have
      not been used in the delivery of nursing care, a number of these therapies have a
      long tradition of use in nursing. Additionally, nurses have conducted research on
      selected complementary therapies. Nursing is in an excellent position to be a
      leader in integrating these therapies into the Western biomedical health model
      and in continuing the research that will provide a better scientific base for the
      use of complementary therapies.

PMID- 11469922
TI  - Nursing as a context for alternative/complementary modalities.
AB  - With increasing consumer and professional interest in alternative and
      complementary care, Registered Nurses (RNs) are incorporating
      alternative/complementary modalities into their practices. While these modalities
      give nurses additional tools to meet client needs, many of these modalities are
      taught and used by non-nursing professionals leading nurses to question if and
      under what circumstances these modalities are included in nursing s scope of
      practice. Exploration of the two major frameworks that define nursing and
      articulate nursing s worldview, Nursing Theory and Nursing s Taxonomies of Care,
      reveals that complementary/alternative modalities can easily be brought into a
      nursing context. Further, professional nursing thought can provide direction to
      the practice of complementary/alternative modalities by adding qualities of
      assessment, reflection, and holism to the performance of the techniques. Examples
      are provided for incorporating alternative/complementary practices into care that
      is clearly identified as professional nursing.

PMID- 11469923
TI  - Quality nursing care celebrates diversity.
AB  - At the beginning of the 21st century, the familiar biomedical health care
      "culture" must accommodate not only persons from diverse cultures, but also
      diverse systems of care. For perhaps the first time in over a century,
      biomedicine must accommodate others rather than require them to assimilate into
      its "culture." This fundamental shift requires nurses to move quickly to develop
      cultural competency as individuals and to provide leadership for this system-wide
      change. Such competence is important when using complementary and alternative
      modalities. This article addresses America s experience with diversity and its
      legacy in today s health indicators; it explores cultural competency and its
      achievement at the individual and system levels; and it discusses the use of
      complementary and alternative treatments that are a part of this health care
      "revolution." Nurses are challenged to shape this reform as did the founder of
      modern nursing 150 years ago.

PMID- 11469924
TI  - Standards for holistic nursing practice: a way to think about our care that
      includes complementary and alternative modalities.
AB  - The Standards of Holistic Nursing Practice were developed by the American
      Holistic Nurses Association (AHNA) as a public statement regarding the practice
      of holistic nursing as a specialty. This article reviews the development of the
      practice standards, and presents the philosophies and values which underpin
      holistic nursing. Certification in the speciality is awarded through the
      American's Holistic Nurses' Certification Corporation (AHNCC) to nurses able to
      demonstrate knowledge and skills described in the Standards. The relationship
      between holistic nursing practice and complementary and alternative modalities is
      discussed.

PMID- 11469925
TI  - Complementary and alternative therapies in nursing education: trends and issues.
AB  - Nurse educators are considering the inclusion of complementary and alternative
      therapies in nursing curricula with increasing frequency, motivated at least in
      part by the ever-increasing public enthusiasm for these therapies. This article
      addresses the differing paradigms between orthodox Western medicine and
      complementary and alternative therapies, describing the research, language,
      educational, legal, financial, and ethical issues related to the use of
      complementary and alternative therapies. Additionally, it presents sources of
      current standards, along with examples of teaching these therapies at the
      undergraduate, graduate and continuing education levels and suggests strategies
      for teaching these therapies.

PMID- 11469926
TI  - Breast cancer risk assessment: Who holds the magic crystal ball?

PMID- 11469927
TI  - From adjuvant therapy to breast cancer prevention: BCPT and STAR.
AB  - The continued widespread prevalence of breast cancer supports placing a high
      priority on research aimed at its primary prevention, particularly among women
      who are at increased risk for developing this disease. The suggestion of
      potential agents for the primary chemoprevention of breast cancer evolved out of
      the treatment setting. Extensive experience with tamoxifen, a first-generation
      selective estrogen receptor modulator (SERM) showing efficacy, first, in the
      treatment of advanced breast cancer and, subsequently, as adjuvant therapy for
      early stage disease established the safety of this agent. Cumulative data from
      multiple adjuvant studies documented the efficacy of tamoxifen in reducing second
      primary breast cancers in the contralateral breast, supporting its potential as a
      chemopreventive agent for breast cancer. The safety and second primary data on
      tamoxifen, together with extensive information on its pharmacokinetics,
      metabolism, and antitumor effects, as well as its potentially beneficial effects
      on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast
      and Bowel Project (NSABP) to select tamoxifen for testing in the first
      prospective randomized phase III trial of the efficacy of a chemopreventive agent
      for preventing breast cancer in women at increased risk of the disease.
      Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1)
      in which 13,388 women > or = 35 years of age who were at increased risk of breast
      cancer according to Gail model risk factors [family history, age, and personal
      history (i.e., age at first birth, age at menarche, previous breast biopsies)]
      were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months
      of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily
      estrogen receptor-positive tumors, by 49% (two-sided p < 0.00001). Tamoxifen
      reduced the risk of noninvasive breast cancer by 50% (two-sided p < 0.002). In
      addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had
      no effect on the rate of ischemic heart disease. As previously shown, the rates
      of endometrial cancer and vascular events increased with tamoxifen. With the P-1
      results establishing tamoxifen as the standard of care for the primary
      chemoprevention of breast cancer in high-risk women, concern over the side
      effects of tamoxifen has prompted a continuing search for an agent that displays
      a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM
      approved for the prevention of osteoporosis in postmenopausal women, displays
      antiestrogenic properties in the breast and possibly the endometrium, and
      estrogenic effects in the bone and on the lipid profile, suggesting it as a
      candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene
      will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and
      Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in
      North America. The plan is to randomize 22,000 postmenopausal women > or = 35
      years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20
      mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and
      noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone
      fractures, and vascular events.

PMID- 11469928
TI  - The rate of breast-conserving surgery for early breast cancer is not influenced
      by the surgical strategy of excisional biopsy followed by the definitive
      procedure.
AB  - Increased emphasis on breast conservation and the primacy of the patient's
      preferences has led to the promotion and increased use of a two-step surgical
      strategy (definitive operation only after a final tissue diagnosis from a biopsy
      done on a previous visit) in the treatment of early breast cancer, with the
      assumption being that this is more conducive to the performance of breast
      conserving surgery (BCS). We sought to test this by examining the effect of the
      surgical strategy (one-step versus two-step) on the operation performed (BCS
      versus mastectomy). A random sample of women with node-negative breast cancer
      diagnosed in 1991 in Ontario was drawn from the Ontario Cancer Registry database
      and matched to the Canadian Institute of Health Information and Ontario Health
      Insurance Plan databases (n = 643). This provided information on the timing and
      nature of all surgical procedures performed as well as patient, tumor, hospital,
      and surgeon characteristics. The surgical strategy was defined as either a one
      step procedure (biopsy and definitive surgery performed at the same time) or a
      two-step procedure (surgical biopsy and pathologic diagnosis, followed by
      definitive surgery at a later date). The axillary lymph node dissection was used
      to define the definitive procedure. BCS was employed in 68% of patients, and this
      did not differ significantly between the one-step and two-step groups (66% versus
      70%). Patients with palpable lesions had a significantly lower rate of breast
      conservation than those with nonpalpable lesions. Other variables associated with
      a lower rate of BCS were larger tumor size, presence of extensive ductal
      carcinoma in situ (DCIS), and central or multifocal tumors. The use of a one-step
      procedure was associated with a patient age of more than 50 years, a palpable
      mass, tumor size larger than 1 cm, previous fine needle aspiration (FNA) biopsy,
      absence of extensive DCIS, and surgery in an academic setting. Breast
      conservation was not affected by the surgical strategy used or the timing of the
      decision, but was associated with several accepted tumor factors. This study
      shows that, contrary to the opinion of some, there is a group of breast cancer
      patients in whom treatment in a one-step manner is appropriate.

PMID- 11469929
TI  - Understanding why contrast enhancement in dynamic MRI is not reproducible:
      illustration with a simple phantom.
AB  - The goal of this work was to verify in a phantom study the necessity of a
      calibration method for comparison in dynamic contrast-enhanced magnetic resonance
      imaging (MRI) examinations. A perspex phantom with a dilution series of Gd-DTPA
      was used to measure the dynamic signal enhancement of a sequence. With nine MRI
      scanners from Bruker (0.23, 0.5, and 2 Tesla), Philips [0.5 and 1.5 Tesla (ACS-NT
      and S15)], and Siemens (0.2, 1.0, and 1.5 Tesla) one 2D FLASH and two 3D FLASH
      experiments were performed under identical measurement conditions. Under
      different measurement conditions (2D and 3D FLASH, TR, TE, FA) different
      characteristics in signal enhancement exist on a scanner. The same measurement
      conditions at different scanners (same magnetic field strength) also result in
      different signal enhancement. Dynamic contrast enhanced MRI examinations from
      different measurement conditions or scanners cannot be compared. To solve this
      problem a calibration is needed.

PMID- 11469930
TI  - Breast cancer: knowledge, attitudes, and practices of female schoolteachers in
      Lagos, Nigeria.
AB  - This article examines the knowledge, attitudes, and practices of female
      schoolteachers concerning breast cancer. A cross-sectional survey was conducted
      among 200 schoolteachers randomly selected from 12 schools in Lagos, Nigeria. A
      self-administered questionnaire was used to investigate their knowledge about the
      symptoms of breast cancer, methods of diagnosis, risk factors, and breast self
      examination. A response rate of 94% (188 respondents) was achieved. Eighty-five
      percent knew breast cancer was a serious disease, but only 53.2% knew that a
      breast lump was the most commonly recognized sign. Other symptoms were even less
      well known. Only 13.8% knew the methods of diagnosis, and knowledge of risk
      factors was also poor. Breast self-examination was practiced by 62% of
      respondents; 11% practiced it on a monthly basis, but only 25% were deemed to
      possess sufficient knowledge about the procedure. One-quarter of participants
      were categorized as possessing a satisfactory knowledge of breast cancer. The
      level of awareness on breast cancer is very low among this group of female
      schoolteachers.

PMID- 11469931
TI  - Elevations of DNA topoisomerase I in invasive carcinoma of the breast.
AB  - DNA topoisomerase I (topo I) is the molecular target of the camptothecin group of
      anticancer drugs. Laboratory experiments indicate that breast cancer cell lines
      are sensitive to these agents and recent clinical trials have suggested that some
      breast cancer patients may respond to drugs targeting topo I. Since it is known
      that cells responding to topo I-targeted drugs have elevated levels of topo I,
      these results suggest that some breast cancers may have elevated expression of
      the enzyme. To test this we used a new topo I monoclonal antibody to immunostain
      22 primary breast cancers and 5 lymph nodes with metastatic disease. Tissue was
      fixed in formalin and paraffin embedded. Expression of topo I was subjectively
      determined by noting the intensity of the immunostain. We found increased
      expression of topo I in 41% (9/22) of the primary tumors. We conclude that
      immunohistochemical staining of breast cancers for topo I can be easily performed
      and may help in defining the molecular parameters of those neoplasms sensitive to
      drugs targeting the enzyme.

PMID- 11469932
TI  - Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph
      node localization.
AB  - Isosulfan blue dye has been used with increasing frequency in localizing sentinel
      lymph nodes in breast cancer patients. Few alternative types of dye have been
      investigated. In a prospective study of 30 patients, methylene blue dye was used
      instead of isosulfan blue dye to localize the sentinel lymph node. The methylene
      blue dye localization technique was successful in 90% of patients. These results
      are similar to those for isosulfan blue dye. This study describes methylene blue
      dye localization as a successful alternative to isosulfan dye in identifying the
      sentinel node in breast cancer patients. The methylene blue dye technique offers
      a substantial cost reduction.

PMID- 11469933
TI  - The inverse relationship between microvessel counts and tumor volume in breast
      cancer.
AB  - Angiogenesis has emerged as an indicator of metastatic potential in invasive
      breast cancer. Exponential tumor growth and the appearance of metastasis are
      observed as new microvessels form. We postulated that the relevance of
      angiogenesis would be enhanced if analyzed as a function of tumor volume rather
      than greatest diameter alone and that microvessel counts would proportionately
      increase as does volume. Since tumors are three-dimensional solids, volume was
      calculated using the formula for an ellipsoid, V = pi/6 (a x b x c). Sixty-four
      tumors < or = 2.5 cm were studied and analyzed in 5 mm incremental ranges. Mean
      microvessel counts did not vary significantly among these tumor size groups.
      However, analysis of microvessel counts as a function of tumor volume decreased
      from 947.1/cm3 (0-0.5 cm) to 18.1/cm3 (2.1-2.5 cm), a greater than 50-fold
      difference. High microvessel density in small cancers supports the notion of
      metastasis as an early event, making these small tumors perhaps ideal targets for
      antiangiogenic agents.

PMID- 11469934
TI  - Multiple unilateral fibroadenomas.
AB  - Fibroadenomas account for the majority of breast biopsies performed today. The
      natural history of fibroadenomas varies. They are usually found as a solitary, 1
      2 cm lesion that is described as being firm, rubbery, nontender, well
      circumscribed, and found in women less than 30 years of age. We present an
      uncommon case of an adolescent female who had a cluster of fibroadenomas in one
      of her breasts, her treatment, and a review of the literature.

PMID- 11469935
TI  - Myofibroblastoma of the male breast: imaging appearance and ultrasound-guided
      core biopsy diagnosis.
AB  - We present the case of a 78-year-old man with the history of a 14-mm, well
      circumscribed mass in the retroareolar region of the right breast. An ultrasound
      guided core biopsy showed myofibroblastoma. The mammagraphic and sonographic
      characteristics of this lesion are described.

PMID- 11469936
TI  - Apocrine poroma of the breast.
AB  - Poromas are sweat gland tumors classically reported to be of eccrine origin.
      However, it is now recognized that poromas may also be derived from apocrine
      glands. There are no prior reports of either type of poroma arising on the
      breast. We report the first case of a poroma of the breast. The lesion was
      localized to the areola of a 70-year-old woman and mimicked an underlying
      neoplasm of the breast. Because the histopathology demonstrated apparent
      continuity of a benign poroma with the infundibula of hair follicles, the
      diagnosis of apocrine poroma was made. The poroma in this case is of apocrine
      derivation. This report demonstrates that apocrine poromas should be considered
      in the clinical differential of acquired lesions on the areola, suggesting an
      underlying breast tumor. Apocrine poromas that are only partially biopsied may
      recur. Moreover, since apocrine poromas may potentially develop into apocrine
      porocarcinomas, analogous to eccrine poromas sometimes transforming into eccrine
      porocarcinomas, apocrine poromas should be completely excised.

PMID- 11469937
TI  - Breast carcinoma with osteoclast-like giant cells.

PMID- 11469938
TI  - Adenosis tumor of the breast containing ductal carcinoma in situ, a pitfall in
      core needle biopsy.

PMID- 11469939
TI  - Combined FNA/core needle biopsy.

PMID- 11469940
TI  - International effort for antiretrovirals: a storm in a teacup?

PMID- 11469941
TI  - Improving adherence to malaria treatment for children: the use of pre-packed
      chloroquine tablets vs. chloroquine syrup.
AB  - Malaria is a major cause of morbidity and mortality among children under five in
      sub-Saharan Africa. Prompt diagnosis and adequate treatment of acute clinical
      episodes are essential to reduce morbidity and prevent complications and
      mortality. In many countries, chloroquine syrup is the mainstay of malaria
      treatment for children under five. Not only is syrup more expensive than tablets,
      adherence to the prescribed dose at home is a problem because mothers use wrongly
      sized measuring devices or have difficulty with the instructions. We investigated
      the impact of introducing pre-packed tablets for children on adherence to
      treatment and compared the total cost of the tablets with that of syrup. Children
      aged 0--5 years diagnosed with malaria at the clinic over a 6-week period
      received either pre-packed tablets or syrup by random assignment. The principal
      caregivers were interviewed at home on day 4 after attending the clinic. Of the
      155 caregivers given pre-packed tablets, 91% (n=141) adhered to the recommended
      dosage, while only 42% (n=61) of 144 who were provided syrup did. Only 20% of
      caregivers who received syrup used an accurate 5 ml measure. The cost of
      treatment with tablets was about one-quarter that of syrup and 62% (n=96) of
      caregivers preferred tablets. Pre-packed chloroquine tablets are a viable
      alternative to syrup.

PMID- 11469942
TI  - A clinical algorithm for the diagnosis of malaria: results of an evaluation in an
      area of low endemicity.
AB  - We conducted a study of 1945 children and 2885 adults who presented with fever to
      a hospital outpatients clinic in an urban area of India order to develop and
      evaluate a clinical algorithm for the diagnosis of malaria. Only 139 (7%)
      children and 349 (12%) adults had microscopically confirmed malaria. None of the
      symptoms or signs elicited from the respondents were good predictors of clinical
      malaria. Simple scores were derived through combining clinical features which
      were associated with slide positivity or were judged by clinicians to be
      important. The best-performing algorithms were a score of 4 clinical features in
      children (sensitivity 60.0% and specificity 61.2%) and a score of 5 in adults
      (sensitivity 54.6% and specificity 57.5%). The clinical features differed and
      algorithm performances were poorer than in previous studies in highly endemic
      areas. The conclusion is that malaria diagnosis in areas of low endemicity
      requires microscopy to be accurate.

PMID- 11469943
TI  - Lymphatic filariasis in Ghana: entomological investigation of transmission
      dynamics and intensity in communities served by irrigation systems in the Upper
      East Region of Ghana.
AB  - We conducted an entomological study to document the effect of irrigation on the
      vectors and transmission dynamics of lymphatic filariasis in the Upper East
      Region of Ghana. Mosquitoes were collected by indoor spraying of houses in a
      cluster of communities located around irrigation projects (Tono and Vea) and
      others without reservoirs (Azoka). Anopheles gambiae s.s. was the dominant
      species and major vector, followed by An. funestus. Anopheles arabiensis
      constituted 9--14% of the An. gambiae complex but none were infective. Culex
      quinquefasciatus was also not infective in these communities. Chromosomal
      examinations showed that >60% (n=280--386) of the An. gambiae s.s. in irrigated
      communities were Mopti forms whilst 73% (n=224) in the non-irrigated area were
      Savannah forms. Infectivity rates (2.3--2.8 vs. 0.25), worm load (1.62--2.04 vs.
      1.0), annual bites per person (6.50--8.83 vs. 0.47) and annual transmission
      potential (13.26--14.30 vs. 0.47) were significantly higher in irrigated
      communities.

PMID- 11469944
TI  - Prevalence of HIV and Chlamydia trachomatis infection in 15--19-year olds in
      rural Tanzania.
AB  - OBJECTIVE: To estimate the prevalence of HIV and Chlamydia trachomatis (CT)
      infections amongst adolescents in rural Mwanza Region, Tanzania and their
      association with demographic variables. DESIGN: Population-based cross-sectional
      survey. METHODS: All 15--19-year olds living in households selected by random
      cluster sampling were invited to participate. After interview, urine was tested
      for HIV and CT. RESULTS: 9445 15--19-year olds were enrolled. HIV prevalence was
      0.6% (95% CI: 0.4--0.8%) in males and 2.4% (95% CI: 2.0--2.8%) in females, and
      increased steeply with age (trend: P < 0.006 and P < 0.001, respectively). After
      adjustment for age, risk of HIV infection was significantly associated with
      female sex (OR=4.3), never having been to primary school in males (OR=2.7), and
      current symptoms of genital discharge (OR=2.3) or genital ulcer (OR=5.3) in
      females. The prevalence of CT was 1.0% (95% CI: 0.8--1.4%) in males and 2.4% (95%
      CI: 2.0-2.9%) in females. After adjustment for age, CT infection was associated
      with female sex (OR=2.4), reported current symptoms of STD (males OR=2.5, females
      OR=1.9) and positive leucocyte esterase (LE) test (males OR=3.1, females OR=2.6).
      Eighty-two percent of males and 79% of females with CT were asymptomatic. There
      was no association between CT and HIV infection in either sex. CONCLUSIONS: There
      is a high prevalence of HIV and CT amongst adolescents, especially young women,
      in this rural population, highlighting the need for effective interventions to
      improve adolescent reproductive health. The high rates of asymptomatic infection
      imply that innovative strategies are needed to reach and treat young people with
      STD.

PMID- 11469945
TI  - Changes in Expanded Program for Immunization coverage for mother and child in
      Krakor, Cambodia 1996--1998.
AB  - We evaluated a training intervention aimed at enhancing the roles of health
      centre staff, Village Health Volunteers (VHVs) and Traditional Birth Attendants
      (TBAs) within the Expanded Program for Immunization (EPI) in the district of
      Krakor, Cambodia. We conducted population-based surveys to determine the coverage
      of the EPI at baseline (1996) and after the intervention (1998), using data from
      health cards for mothers and their children and history data. Statistically
      significant changes over the 2-year period were apparent for tetanus, BCG, polio
      and DTP, supporting the positive impact the training intervention had on
      immunization coverage in the district.

PMID- 11469946
TI  - The influence of prematurity and low birthweight on transplacental antibody
      transfer in a rural West African population.
AB  - OBJECTIVE: To determine the influence of prematurity and low birthweight (LBW) on
      transplacental antibody transfer. METHOD: In a physician-blinded, cross-sectional
      study of 213 mother--baby pairs in the labour ward of Bansang Hospital, The
      Gambia, paired maternal and cord serum samples were tested for specific IgG
      antibody titres for measles virus (MeV), herpes simplex virus type 1 (HSV1),
      respiratory syncytial virus (RSV), varicella-zoster virus (VZV), tetanus toxoid
      (TT) and diphtheria toxoid (DT) antigens using enzyme linked immunosorbent assay
      (ELISA). RESULTS: Prematurity was significantly associated with reduced placental
      antibody transfer for MeV, HSV1, TT, DT, RSV and VZV. Maternal antibody transfer
      for MeV, HSV1, TT, DT, RSV and VZV was significantly lower in neonates with LBW
      than in babies with adequate birthweight (ABW). CONCLUSION: Materno--foetal
      transfer of antibodies is impaired in prematurity and LBW babies in this Gambian
      population. Reduction in antibody transfer may further predispose these already
      vulnerable neonates to bacteria and viral infections. Therefore, alternative
      vaccination strategies, including earlier vaccination schedules, are needed to
      provide better protection to these young infants.

PMID- 11469947
TI  - Extending anthelminthic coverage to non-enrolled school-age children using a
      simple and low-cost method.
AB  - School health programmes are the basis of the strategy defined by WHO to reduce
      morbidity due to soil-transmitted nematodes and schistosomes in school age
      populations in developing countries. However, low rates of school enrollment can
      be a major factor limiting their success. In the present study enrolled children
      were informed by teachers on the date of the next deworming campaign and were
      invited to pass along this information to parents, siblings and friends of school
      age. On the day of the deworming campaign, teachers were instructed to administer
      anthelminthics to enrolled and not enrolled school-age children present at
      school. In the month following the treatment day, information about coverage was
      collected by questionnaire in 257 households in two regions of Unguja Island,
      Zanzibar. Over 89% of school age children resulted treated (98.9% of those
      enrolled plus 60% of those not enrolled). The additional cost of treating non
      enrolled is limited to the cost of providing additional doses of anthelminthic
      drug in each school. Non-enrolled school age children can easily, successfully
      and inexpensively included in school based deworming campaign. Managers of
      control programmes are invited to test this method adapting it in their
      particular and cultural environment.

PMID- 11469949
TI  - Hypothetical and actual willingness to pay for insecticide-treated nets in five
      Nigerian communities.
AB  - OBJECTIVES: To determine the hypothetical and actual willingness of households to
      pay (WTP) for insecticide-treated nets (ITNs), and compare these in areas with
      and without previous exposure to free ITNs. METHODOLOGY: The contingent valuation
      method was used to determine the willingness of the heads of 1908 randomly
      selected households from five communities in south-east Nigeria to pay for two
      sizes of ITNs. Two communities previously had free access to ITNs. Validity was
      assessed using multiple regression analyses, and by offering ITNs for sale to 200
      randomly selected people drawn from the original sample. The data was collected
      between March and September 1998. FINDINGS: Most respondents were willing to pay
      for ITNs: Mbano (93.26%), Ugwogo (97.69%), Orba (83.24%), Alor-uno (95.37%), and
      Ibagwa-ani (87.34%). In multivariate analyses, WTP was significantly associated
      with the number of people living in a household, sex of the respondent, average
      yearly expenditure on gifts and the type of savings scheme (P < 0.05). Some of
      the residences were also statistically significant in the two models used, and
      those with prior exposure to free ITNs were negatively related to WTP. Seventy
      six percent of those who were hypothetically willing to pay actually purchased
      them, and the WTP technique correctly predicted the choices of 80% of the
      respondents. CONCLUSION: There was good evidence that stated WTP could be
      translated into actual WTP. However, peoples' perception of affordability of the
      nets and its link to their WTP needs further exploration. The WTP technique is a
      potentially valid tool for market research in healthcare, as it was able to
      predict the direction of actual WTP for the ITNs. The hypothetical WTP amounts
      could be used as guide to know either the optimal price to charge for the ITNs or
      the level of subsidy to introduce.

PMID- 11469948
TI  - Dynamics of egg counts and circulating antigen levels in a recent Schistosoma
      mansoni focus in northern Senegal.
AB  - Serum circulating anodic antigen (CAA) levels were compared with faecal egg
      counts in four subsequent population samples, randomly selected at 8-month
      intervals, in a recent Schistosoma mansoni focus in northern Senegal. In all four
      samples, antigen levels showed the same age-intensity profiles as egg counts,
      with a strong decline in adults. Also across population samples, a consistent
      relationship was found between egg counts and antigen levels. Assuming the level
      of CAA to be a direct reflection of worm burden, these findings support the idea
      that the observed egg count patterns and levels indeed reflect dynamics of worm
      burdens, and not of egg excretion or worm fecundity. Remarkably similar levels of
      both egg counts and CAA were observed in the first and last sample, collected in
      the same season (August--September), but 2 years apart. This suggests that a
      steady state of S. mansoni infection had already been reached shortly after the
      onset of the epidemic in this focus (3 years). Significantly lower infection
      levels were found in the intermediate population samples collected in January and
      April. The differences in infection levels across the four population samples may
      be because of seasonal transmission patterns. They would indicate a substantial
      turnover of worm populations, with an estimated average life span of only 7
      months, probably less, in this recently emerged, intense S. mansoni focus.

PMID- 11469950
TI  - Susceptibility to development of Mycobacterium ulcerans disease: review of
      possible risk factors.
AB  - Mycobacterium ulcerans disease, also known as Buruli ulcer (BU), is a disease of
      subcutaneous fat tissue. BU is prevalent in riverine and swamp areas of the
      tropical zone in Africa, Asia and South America, and a few scattered foci in
      Australia. The mode of transmission of M. ulcerans has not been fully elucidated,
      but inoculation into the subcutaneous tissues probably occurs through penetrating
      skin trauma. BU has not been linked with HIV infection. Antimycobacterial drug
      treatment is ineffective, and treatment is surgical. Patients eventually develop
      scars and contractures, with resulting disabilities, and the disease imposes a
      large burden on affected populations. The incidence of BU has dramatically
      increased in West African countries over the last decade. There is an urgent need
      for research into host and environmental risk factors for BU in order to develop
      effective strategies to combat this disease. We review possible genetic host
      susceptibility factors for BU that are relevant in other mycobacterial diseases:
      natural resistance-associated macrophage protein-1 (NRAMP-1), HLA-DR, vitamin D3
      receptor, mannose binding protein, interferon-gamma (IFN-gamma) receptor, tumour
      necrosis factor alpha (TNF-alpha), interleukin (IL)-1 alpha, 1 beta and their
      receptor antagonists; and IL-12. Schistosoma haematobium infection is highly
      endemic in many BU foci in West Africa, with a striking increase in transmission
      after river dams were constructed. This observation, and the observations from
      interaction of schistosomiasis and tuberculosis, have fueled our hypothesis that
      schistosomiasis is a risk factor for BU by driving the host immune response
      towards a predominantly Th-2 pattern, away from a Th-1 preponderant protection
      against mycobacterial infection. If the latter hypothesis is confirmed, enhanced
      schistosomiasis control should impact on BU.

PMID- 11469951
TI  - Viewpoint: medical infertility care in low income countries: the case for concern
      in policy and practice.
AB  - Based on published, 'grey' and anecdotal information, this paper explores some
      aspects of infertility, its medical treatment and their burden in poor countries.
      Many cases of infertility result from sexually transmitted infections (STI) and
      unsafe abortion and there is no doubt that their prevention and adequate
      treatment are of utmost importance, especially as effective infertility
      treatment, if any, comes at a high price for the consumer, materially as well as
      physically. Medical infertility interventions are apt to fail a free market of
      provision because of major information asymmetry. This renders patients in low
      resource countries prone to exploitation, potentially damaging practices and
      waste of their savings. The authors argue that in countries struggling with
      limited funds and a range of pressing public health problems, public investment
      in infertility treatment should not have priority. But governments should take an
      active role in quality control and regulation of treatment practice, as well as
      invest in counseling skills for lower-level reproductive health staff to achieve
      rational referral of patients.

PMID- 11469952
TI  - Tract microflora in Saudi patients with cholelithiasis.
AB  - OBJECTIVES: To identify the microflora in the gallbladder of patients undergoing
      laparoscopic cholecystectomy for gallstones, and the antibiotic susceptibility
      pattern of the isolates, as well as the usefulness of Gram staining of bile at
      the time of operation. METHODS: Bile samples were obtained from 112 patients
      undergoing elective laparoscopic cholecystectomy for gallstones and inoculated
      directly into aerobic and anaerobic blood culture bottles in the operating
      theatre. Samples were also collected in sterile universal containers for Gram
      staining of a centrifuged deposit. Isolates were identified and their in-vitro
      susceptibilities determined by Kirby Bauer technique. RESULTS: Of 112 bile
      samples examined, 28 (25%) were culture positive, four of which contained more
      than one organism. The most common organisms isolated were Escherichia coli 9
      (28.1%), Enterococcus faecalis 5 (15.6%) and Pseudomonas aeruginosa 3 (9.4%). In
      one sample we found Aeromonas hydrophilia and Enterobacter cloacae. No anaerobes
      were detected but Candida albicans was isolated in one case. In 19 bile samples
      (67.8%) organisms were identified on Gram stain. Positive bile cultures were
      found statistically significant (P < 0.05) in patients over the age of 50
      (13/32), in patients who developed post-operative fever (6/12) and patients who
      developed leucocytosis (5/6). CONCLUSION: Age over 50 years was the only
      significant pre-operative factor associated with positive bile cultures (P <
      0.05). In view of the microflora of the gallbladder and the susceptibility
      pattern of our isolates we would suggest that antibiotic prophylaxis recommended
      for laparoscopic cholecystectomy for gallstones needs to be reviewed and the role
      of bacteribilia in the surgical management of cholelithiasis requires further
      study.

PMID- 11469968
TI  - Hyperlipidemia in Chronic Cholestatic Liver Disease.
AB  - Hyperlipidemia with a marked increase of low-density lipoprotein (LDL) and high-
      density lipoprotein (HDL) cholesterol levels is a common feature in patients with
      chronic cholestatic liver disease. Excess morbidity and mortality from
      cardiovascular disease has not been reported in these patients. This may be due
      to the particular lipoprotein pattern observed during chronic cholestasis,
      characterized by elevated serum HDL cholesterol, which may have a
      cardioprotective effect. However, in a subgroup of patients with chronic
      cholestasis, hyperlipidemia is characterized by markedly elevated LDL levels with
      normal or low HDL levels, probably reflecting hypercholesterolemia with
      coexisting familial and nutritional origins. Ursodeoxycholic acid, the only drug
      approved for the treatment of chronic cholestatic liver diseases, has been shown
      to slightly decrease serum cholesterol concentrations. However, the extent of LDL
      reduction by ursodeoxycholic acid may be insufficient to protect this subgroup of
      patients from increased cardiovascular risk. Patients in this subgroup probably
      would benefit from dietary modification, weight loss, and the administration of
      specific lipid-lowering drugs. Cholestyramine, which is the first-line treatment
      for pruritus in chronic cholestasis, may be also indicated for its cholesterol
      lowering capacity in patients with hypercholesterolemia who complain of pruritus.
      Administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase
      inhibitors (simvastatin or pravastatin, 20 mg/d) should be limited to
      hypercholesterolemic patients with mild chronic cholestatic liver diseases in
      whom HDL serum levels are below the protective range or if additional risk
      factors for cardiovascular diseases are present.

PMID- 11469969
TI  - Choledochal Cystic Diseases.
AB  - Cystic disease of the intrahepatic and extrahepatic bile ducts results in rare
      malformations with a variable presentation. The majority of patients present
      during childhood with symptoms of abdominal pain, cholangitis, and an abdominal
      mass. A palpable mass is unusual in adults, and adult patients tend to present
      with recurrent cholangitis, pancreatitis, or rarely portal hypertension. The
      cause of this disorder also is debated, with both congenital and acquired origins
      postulated. The gold standard for the treatment of choledochal cysts is complete
      excision with the establishment of biliary flow into the gastrointestinal tract.
      The well described malignant potential of the cyst and the high rate of recurrent
      cholangitis with internal drainage procedures mandate cyst excision when
      possible. In the event of extensive scarring or malignant changes of the cyst,
      the posterior wall of the cyst may be left in situ to avoid endangering the
      portal vessels, which are found posteriorly. Alternatively, various endoscopic or
      percutaneous interventions may provide symptomatic relief. However, every effort
      should be directed towards complete resection of the cyst and the re
      establishment of biliary-enteric continuity.

PMID- 11469970
TI  - Chronic Visceral Right Upper Quadrant Pain Without Gallstones.
AB  - Patients with chronic visceral right upper quadrant pain without gallstones can
      be broadly categorized into two groups: patients with gallbladder dyskinesia, and
      patients with sphincter of Oddi dysfunction (SOD). Treating patients with these
      disorders is often challenging to clinicians due to the difficulty at arriving at
      a definite diagnosis, and the lack of efficacy of various treatment modalities.
      The only real treatment option for patients with gallbladder dyskinesia is
      cholecystectomy; however, the results are difficult to predict in an individual
      patient. Patients with SOD can be approached according to a classification that
      at least partially reflects the underlying pathophysiology. Patients with type I
      SOD have underlying papillary stenosis, and benefit from empiric sphincterotomy.
      Patients with type II SOD may have muscle spasm as predominant pathophysiology;
      this group of patients benefit from sphincterotomy only if increased sphincter
      pressure is demonstrated by sphincter of Oddi manometry. Patients with type III
      SOD may have visceral hyperalgesia; a trial of antidepressants or a therapeutic
      trial with botulinum toxin injection into the ampulla should be considered prior
      to more invasive endoscopic therapy.

PMID- 11469971
TI  - Choledocholithiasis in the Setting of Portal Hypertension.
AB  - The successful management of biliary lithiasis in patients with cirrhosis depends
      on the degree of liver dysfunction. Patients with Child-Pugh class A or B hepatic
      reserve have excellent prognoses. Endoscopic spincterotomy is first-choice
      treatment for cirrhotic patients with choledocholithiasis. Endoscopic
      sphincterotomy can be performed in patients with Child-Pugh class A, B, or C
      hepatic function. Medical treatment with contact solvents is contraindicated in
      patients with pigment stones or calcified stones.

PMID- 11469972
TI  - Bacterial Cholangitis.
AB  - The treatment of acute bacterial cholangitis requires broad-spectrum antibiotics
      to cover against gram-negative aerobic enteric organisms (Escherichia coli,
      Klebsiella species, and Enterobacter species), gram-positive Enterococcus and
      anaerobic bacteria (Bacteroides fragilis and Clostridium perfringens).
      Approximately 20% of patients with acute cholangitis fail to respond to
      conservative treatment with antibiotic therapy and require urgent biliary
      decompression, which is the mainstay of therapy. This is best accomplished by
      endoscopic retrograde cholangiopancreatography (ERCP) and placement of a
      nasobiliary drainage tube or a large bore (10 F or larger) indwelling plastic
      stent. Alternative therapy includes percutaneous transhepatic biliary drainage or
      surgical biliary decompression, but these carry a significantly higher morbidity
      and mortality. Supportive care includes intravenous fluid hydration to prevent
      renal failure and close monitoring of vital signs for determination of potential
      septicemia.

PMID- 11469973
TI  - Small Intestinal Infections.
AB  - The differential diagnosis of small intestinal infections is broad, making the
      identification and management of these disorders challenging. The majority of
      cases of acute diarrhea are self-limited and do not require diagnostic evaluation
      or treatment. Most patients do not require specific therapy, and treatment should
      focus on fluid and electrolyte replacement. In patients with severe, persistent,
      or chronic diarrhea, a careful medical history and routine stool testing are
      helpful in determining the cause. Pathogen-specific therapy should be given in
      patients in whom a pathogen is identified. In those without an identifiable
      pathogen, antidiarrheal agents are helpful in reducing the number of bowel
      movements and preventing further dehydration. Endoscopy may be helpful in
      patients with severe diarrhea and a negative stool evaluation, particularly in
      HIV-infected patients with chronic diarrhea. Surgery has a limited role in the
      management of small intestinal infections, but may be lifesaving in patients with
      intestinal perforation or small bowel obstruction.

PMID- 11469974
TI  - Portal Hypertensive Gastropathy and Gastric Antral Vascular Ectasia.
AB  - Portal hypertensive gastropathy (PHG) causes both acute and chronic blood loss
      from the gastrointestinal tract in patients with portal hypertension. Gastric
      antral vascular ectasia (GAVE) is a distinct condition also associated with
      portal hypertension that can cause acute and chronic upper gastrointestinal blood
      loss. These conditions frequently, but not invariably, are diagnosed by upper
      endoscopy. Although they are fairly prevalent, only 15% to 20% of subjects
      experience symptomatic gastrointestinal blood loss. Acute gastrointestinal
      bleeding from PHG should first be treated with octreotide (100 mg bolus
      intravenously, followed by a 50 mg/h continuous intravenous infusion). If the
      bleeding does not stop or slow down appreciably within 24 to 48 hours,
      propranolol may be administered orally to those patients who are hemodynamically
      stable. Propranolol should be started at 40 mg/d orally in two divided doses. If
      the patient can tolerate the propranolol and is still bleeding, the dosage may be
      titrated up to the maximum tolerated amount. For those subjects who are unable to
      tolerate beta-blockers or continue to bleed despite beta-blocker therapy,
      transjugular intrahepatic portosystemic shunt (TIPS) is the next line of
      treatment. Portal decompressive surgery is reserved for those who are not
      candidates for TIPS and where the appropriate expertise is available. Prevention
      of chronic gastrointestinal blood loss from PHG should be attempted with beta
      blockers, with the dosage titrated up to achieve a resting heart rate of
      approximately 60 beats per minute. In patients who do not respond to beta
      blockers, a TIPS should be placed. The role of long-acting release octreotide in
      this setting is experimental. The primary treatment of actively bleeding GAVE as
      well as recurrent bleeding from GAVE is endoscopic ablation of the lesion using
      either argon plasma coagulation, neodymium:yttrium-aluminum-garnet (Nd:YAG)
      laser, or heater probe. TIPS and beta-blockers are ineffective for the long-term
      prevention of recurrent bleeding from GAVE. For selected patients with severe
      recurrent bleeding or uncontrollable acute bleeding from GAVE, an antrectomy with
      Billroth I anastomosis may be considered.

PMID- 11469975
TI  - Vascular Malformations of the Small Intestine.
AB  - Vascular malformations of the small bowel are uncommon, yet remain a cause of
      gastrointestinal bleeding in up to 5% of patients with gastrointestinal
      hemorrhage. The diagnosis of these lesions is suspected in patients with a
      gastrointestinal source of blood loss with a negative upper endoscopy and
      colonoscopy. Enteroscopy remains the mainstay in diagnosing these lesions.
      Therapeutic options include endoscopic coagulation, pharmacologic agents
      (hormones, octreotide, iron replacement), and occasionally surgery. Pharmacologic
      and endoscopic treatments are discussed.

PMID- 11469976
TI  - Gastric Dysmotility and Gastroparesis.
AB  - Nutrition support in gastroparesis begins with encouraging smaller volume, low
      fat, low-fiber meals and, if necessary, liquid caloric supplements. There should
      be a low threshold for placing a jejunal feeding tube either by laparoscopy or
      mini-laparotomy. Parenteral nutrition should be used only briefly during
      hospitalization and not encouraged or sustained as an outpatient. Metoclopramide
      is now the prokinetic of choice for patients who can tolerate this agent;
      subcutaneous administration is an important method that allows for continued
      guaranteed absorption. Low-dosage erythromycin also has a prokinetic role alone
      or in combination with metoclopramide. Domperidone, a centrally acting antiemetic
      and prokinetic, is only be available to US citizens who can access sources in
      Canada or Mexico. Antiemetics should be used extensively because nausea is a very
      severe debilitating symptom, which is under-appreciated and under-treated by
      physicians. We recommend scopolamine patches to gain maximal absorption, in spite
      of vomiting and unpredictable oral intakes. The 5-hydroxytryptamine-3 (5-HT3)
      antagonists ondansetron and granisetron are the most powerful agents. Relief
      bands using the P6 acupuncture point are useful adjunct. Special vigilance should
      be paid to situations that can undermine medical therapy or result in
      breakthrough symptoms, such as hyperglycemic events in patients with diabetes,
      migraine headaches, cyclic nausea and vomiting, menstrual cycles, rumination
      syndrome (psychogenic vomiting), and elevated herpes simplex titers. Most
      excitingly, the era of gastric electrical stimulation has arrived for patients
      not responding to standard medical therapy. The dramatic improvement in nausea
      and vomiting, as well as a sustained evidence of improved quality of life,
      gastric emptying, nutritional status, and decreased hospitalizations by this
      device are documented by long-term follow-up of more than a year for patients in
      this country and world-wide.

PMID- 11469977
TI  - Immunomodulator Therapy in Inflammatory Bowel Disease.
AB  - 6-Mercaptopurine and its prodrug counterpart, azathioprine, have proven efficacy
      in the induction and maintenance of remission, fistula closure, and steroid
      sparing in patients with Crohn's disease. Long-term follow-up has demonstrated
      the safety of the purine analogues, with no increased risk of malignancy. For
      patients with Crohn's disease intolerant or unresponsive to azathioprine or 6
      mercaptopurine, methotrexate has emerged as an effective alternative. In patients
      with severe ulcerative colitis, intravenous cyclosporine is highly efficacious in
      the short term, and with the addition of azathioprine or 6-mercaptopurine to oral
      cyclosporine, long-term remission rates of 60% to 70% can be achieved.
      Azathioprine or 6-mercaptopurine therapy is effective in patients with steroid
      dependent or steroid-refractory colitis and is valuable in maintaining remission.
      Neither methotrexate nor cyclosporine has been shown to be effective for
      maintenance therapy in patients with ulcerative colitis. Current data are
      insufficient to recommend routine use of genetic or enzymatic testing of
      thiopurine methyltransferase or measurements of blood 6-thioguanine metabolites
      to guide 6-mercaptopurine or azathioprine dosing.

PMID- 11469978
TI  - Nutritional Treatments in Inflammatory Bowel Disease.
AB  - The role of nutritional intervention in inflammatory bowel disease (IBD) is
      twofold: first, as primary therapy for patients with acute Crohn's disease;
      second, as an invaluable adjunctive therapy for the correction and maintenance of
      nutritional status for both patients with Crohn's disease and those with
      ulcerative colitis. Careful nutritional monitoring and appropriate nutritional
      intervention throughout all stages of disease should be an integral part of the
      multidisciplinary management approach to IBD. In terms of primary therapy,
      polymeric and elemental enteral diets are an effective therapy for patients with
      acute Crohn's disease, offering an unrivaled safety profile and significant
      nutritional benefits. Enteral diets should be considered as primary therapy in
      children with Crohn's disease, especially in those with poor nutritional status
      or growth impairment, and in patients with severe drug-induced side effects.
      Total parenteral nutrition (TPN) does not have a primary therapeutic role in
      patients with IBD.

PMID- 11469979
TI  - Surgical Management of Inflammatory Bowel Disease.
AB  - Surgery continues to be a central component in the treatment of patients with
      inflammatory bowel disease (IBD). The most important aspect of caring for
      patients with IBD is a close and ongoing interaction between the surgeon and
      gastroenterologist both before and after surgery. Surgery in patients with
      chronic ulcerative colitis (CUC) is curative. In the appropriate patient, we
      recommend proctocolectomy with ileal pouch anal anastomosis (IPAA). In contrast,
      patients with Crohn's disease cannot be cured with surgery. Instead, surgery is
      used in conjunction with maximal medical therapy to treat symptoms of the disease
      and improve the patient's quality of life. Surgical interventions should be
      limited in scope. Small bowel disease should be treated with either limited
      resection or strictureplasty, if possible, to conserve bowel length. For limited
      involvement of the colon, segmental resection yields good results. Minimal
      surgical intervention, drainage of abscesses, placing draining setons, and
      aggressive medical therapy is recommended as treatment of perianal Crohn's
      disease.

PMID- 11469980
TI  - Extraintestinal Complications of Inflammatory Bowel Disease.
AB  - Extraintestinal complications of inflammatory bowel disease (IBD) are often
      secondary to the underlying disease. Therefore, the first priority is to get
      active IBD into remission with medications, since surgery for IBD is not
      indicated for the treatment of extraintestinal complications. Symptoms of
      extraintestinal complications usually can be treated with simple agents; the
      treatment of patients with refractory symptoms and the use of more complex drug
      regimens should be done in cooperation with specialists on affected organ
      systems. Careful consideration of prescribed drugs is necessary because they may
      negatively influence the course of IBD.

PMID- 11469981
TI  - Inflammatory Bowel Disease During Pregnancy.
AB  - The management of both male and female patients with inflammatory bowel disease
      (IBD) who wish to have a baby is challenging. For women, the most important
      factor to bear in mind is that the outcome of pregnancy is largely influenced by
      disease activity at the time of conception. Women with quiescent disease are
      likely to have an uncomplicated pregnancy with the delivery of a healthy baby,
      whereas women with active disease are more likely to have complications such as
      spontaneous abortions, miscarriages, stillbirths, and exacerbation of the
      disease. This is more true of patients with Crohn's disease than of patients with
      ulcerative colitis. Although the safety of medications used during pregnancy is
      an important issue, the impact of the medications used to treat IBD is less
      important in comparison to disease activity itself. 5-Aminosalicylic acid (5-ASA)
      products appear to be safe during pregnancy; corticosteroids are probably safe; 6
      mercaptopurine and azathioprine should be used with caution; and methotrexate is
      contraindicated. There are inadequate data on the use of infliximab during
      pregnancy. In regard to men with IBD, the disease itself does not seem to have
      any negative impact on fertility. However, there is controversy about the effects
      of using 6-mercaptopurine and azathioprine prior to and during fertilization. In
      view of possible adverse pregnancy outcomes, it would be prudent to withhold 6
      mercaptopurine and azathioprine therapy in men with IBD for 3 months prior to
      conception, when feasible. Most IBD medications should be continued before,
      during, and after pregnancy, with careful attention to the known cautions and
      exceptions. If IBD in a pregnant patient is in remission, the prognosis for
      pregnancy is the same as if she did not have IBD. Active disease should therefore
      be treated aggressively and remission accomplished before pregnancy is attempted.
      Similarly, a woman who unexpectedly becomes pregnant while her IBD is active
      should be treated aggressively, as remission remains the greatest investment for
      a favorable pregnancy outcome.

PMID- 11469982
TI  - Diversion Colitis.
AB  - Management of the patient with diversion colitis is dependent upon both patient
      and disease-related factors. Patients in whom diversion is not permanent, who
      desire stoma closure, and who have an acceptable surgical risk should undergo re
      establishment of intestinal continuity. Asymptomatic, high-risk surgical
      candidates need only undergo periodic, regular endoscopic surveillance of both
      the functional and nonfunctional large bowel according to currently accepted
      screening guidelines. Most symptomatic patients in whom the diversion is
      permanent can be treated successfully with steroid enemas, 5-aminosalicylic acid
      enemas or suppositories, or short-chain fatty acid enemas. If diversion is
      permanent, medical treatment is unsuccessful, and symptoms persist, acceptable
      surgical candidates should undergo resection of the excluded bowel.

PMID- 11469983
TI  - Fecal Incontinence.
AB  - Fecal incontinence is a socially devastating clinical condition. Initial
      symptomatic treatment includes exclusion of foods that precipitate the problem,
      increased use of fiber, and drug therapy with loperamide. Persistence of
      incontinence after these lifestyle modifications requires the physician to
      evaluate the internal and external anal sphincters. Anal endosonography and
      manometry provide an evaluation of sphincter structure and function. If an
      isolated muscle defect is seen, sphincteroplasty can be tried. If this surgical
      procedure is not indicated, biofeedback may be an option. Biofeedback should be
      considered for patients with neurogenic fecal incontinence, a weak but
      structurally intact external sphincter, or a decreased ability to perceive rectal
      distention. Muscle transposition to create a neosphincter should be offered only
      by surgeons with extensive experience performing this surgery. Because of the
      cosmetic sequela of colostomy, this surgery is often considered as a last-step
      procedure, despite being safe and effective.

PMID- 11469984
TI  - Refractory Inflammatory Bowel Disease.
AB  - Therapeutic options for refractory colonic inflammation in patients with
      ulcerative colitis or Crohn's disease have recently been augmented by the
      introduction of biologic therapies. Intravenous corticosteroids and cyclosporin A
      remain the standard therapies for severe ulcerative colitis. Monoclonal
      antibodies directed at tumor necrosis factor alfa (TNF-alpha) have proven to be
      most efficacious in patients with severe or refractory Crohn's disease.
      Immunomodulatory therapy with azathioprine, 6-mercaptopurine, or methotrexate has
      demonstrated efficacy for maintenance of remission in patients with refractory
      ulcerative colitis or Crohn's disease. The use of experimental biologic agents
      may be considered for those patients who fail to respond to or remain dependent
      on corticosteroids. Surgical intervention is indicated for patients with severe
      colitis who fail to respond to medical therapy or develop life-threatening
      complications such as perforation or toxic megacolon.

PMID- 11469985
TI  - Anal Carcinoma.
AB  - Carcinoma of the anus is a rare malignancy that usually is diagnosed at an
      advanced stage, in spite of being easily visible and accessible. Its treatment
      has evolved from being mainly surgical to one consisting of chemotherapy (with
      fluorouracil and mitomycin) and radiation (megavoltage linear accelerator therapy
      delivering between 40 to 50 Gy). Local surgical excision is most often performed
      for either carcinoma in situ or microinvasive lesions of the anal margin. Radical
      resection is indicated for patients with residual disease following
      chemoradiation or for recurrent disease.

PMID- 11469986
TI  - Postinfectious Irritable Bowel Syndrome.
AB  - Postinfectious irritable bowel syndrome (PI-IBS) should be considered in patients
      who present with a change in bowel habits or an onset of new abdominal pain or
      discomfort following a recent confirmed or presumed exposure to infectious
      organisms, or in those who have recently returned from a tropical or developing
      country. In patients who are greatly distressed by their symptoms, an extended
      workup early in the course of their illness may give physician and patient
      confidence in focusing on IBS. The author favors a proactive, multicomponent
      approach to management, as it gives the physician and patient a sense of control.
      Treatment should include stress management, dietary advice to minimize exposure
      to trigger foods, and pharmacotherapy to alleviate anxiety and target disturbed
      physiology.

PMID- 11469987
TI  - Outlet Dysfunction Constipation.
AB  - The diagnosis of outlet dysfunction constipation in patients with idiopathic
      constipation that responds poorly or not at all to conservative measures, such as
      fiber supplements, fluids, and stimulant laxatives, is based upon diagnostic
      testing. These tests include colonic transit of radio-opaque markers, anorectal
      manometry or electromyography, barium defecography, and expulsion of a water
      filled balloon. The literature suggests that conditions such as pelvic floor
      dyssynergia exist but may be over-diagnosed as a laboratory artifact. In our
      laboratory, we screen patients with balloon expulsion studies, and then test for
      dyssynergia only if the result of the balloon expulsion test is abnormal. In my
      opinion, anal sphincter electromyogram and manometry are equivalent in
      establishing the diagnosis. Barium defecography is helpful in making a diagnosis
      of a rectocele, but I prefer to document that vaginal pressure on the rectocele
      significantly improves rectal evacuation. Manometry also helps to establish the
      presence of megarectum, hypotonia, and weak expulsion efforts. Conceptually,
      biofeedback training, which incorporates simulated defecation, is the most
      logical approach to pelvic floor dyssynergia. It incurs no risk and benefits 60%
      to 80% of patients. The drawbacks are the time-intensive nature of the therapy
      and the short-term costs, which are offset if there is sustained benefit. There
      is no evidence that biofeedback is helpful in children with constipation. Habit
      training has established benefits, but recurrences are frequent and long-term
      reinforcement is helpful to maintain success. Laxatives and enemas are adjunctive
      therapies in both habit training and biofeedback. Surgery is effective in those
      uncommon patients with physiologically significant rectoceles, but surgical
      division of the puborectalis muscle is risky and unproven. Likewise, botulinum
      toxin injection into the puborectalis is unproven, but the effects are rarely
      permanent should incontinence occur. Diagnostic measures and therapeutic success
      are enhanced when patients are seen in centers experienced with the evaluation of
      these disorders.

PMID- 11469988
TI  - Diarrhea- and Constipation-predominant Irritable Bowel Syndrome.
AB  - Irritable bowel syndrome (IBS) has a reputation for being hard to treat, trivial,
      and often psychologic in origin. Furthermore, there currently appears to be
      almost more of a stigma attached to being diagnosed as having IBS than a
      depressive illness. Thus, it is not surprising that patients with this syndrome
      become distressed by the attitudes they encounter, particularly as we now know
      that this condition can substantially impair one's quality of life. The problem
      with effective management is that there is no "standard treatment" and therapy
      has to be targeted to the symptoms of the individual patient. This frequently
      proves to be time consuming and also may involve some degree of trial and error.
      However, when all the issues surrounding IBS are addressed in a sympathetic and
      positive manner, these patients can be surprisingly rewarding to treat.

PMID- 11469989
TI  - Slow-transit Constipation.
AB  - Idiopathic slow-transit constipation is a clinical syndrome predominantly
      affecting women, characterized by intractable constipation and delayed colonic
      transit. This syndrome is attributed to disordered colonic motor function. The
      disorder spans a spectrum of variable severity, ranging from patients who have
      relatively mild delays in transit but are otherwise indistinguishable from
      irritable bowel syndrome to patients with colonic inertia or chronic megacolon.
      The diagnosis is made after excluding colonic obstruction, metabolic disorders
      (hypothyroidism, hypercalcemia), drug-induced constipation, and pelvic floor
      dysfunction (as discussed by Wald ). Most patients are treated with one or more
      pharmacologic agents, including dietary fiber supplementation, saline laxatives
      (milk of magnesia), osmotic agents (lactulose, sorbitol, and polyethylene glycol
      3350), and stimulant laxatives (bisacodyl and glycerol). A subtotal colectomy is
      effective and occasionally is indicated for patients with medically refractory,
      severe slow-transit constipation, provided pelvic floor dysfunction has been
      excluded or treated.

PMID- 11469990
TI  - Nonulcer Dyspepsia.
AB  - There is currently no effective treatment for patients with nonulcer dyspepsia.
      Helicobacter pylori eradication has no beneficial effect on dyspeptic symptoms.
      Proton pump inhibitors are superior to placebo in the subset of patients with
      epigastric pain as the predominant symptom. H(2 )Receptor antagonists have no
      effect. Patients with dysmotility-like dyspepsia should be treated first with
      prokinetics. Unfortunately, cisapride no longer can be used to treat patients
      with functional dyspepsia because of reports of serious cardiovascular side
      effects and subsequent withdraw from the US market. Therefore, metoclopramide (or
      domperidone, if available) should be given. Treatment with motilides has no use
      in the relief of symptoms, even in patients with delayed gastric emptying. If the
      initial therapy has no effect after 4 weeks, switch treatment (eg, from proton
      pump inhibitor to metoclopramide or vice versa). If both of these pharmacologic
      therapies fail, consider treatment with an antidepressant (or with buspirone, an
      anxiolytic agent) or psychotherapy.

PMID- 11469991
TI  - Psychologic Therapies for Irritable Bowel Syndrome.
AB  - The treatment of patients with irritable bowel syndrome (IBS) is a difficult
      task, as the results from therapy with pharmacologic agents have been
      disappointing. Psychologic treatments, in particular cognitive behavior therapy,
      hypnotherapy, and dynamic psychotherapy have all shown to be effective in the
      treatment of patients with IBS. Underpinning all these treatments is a clear
      understanding of a biopsychosocial model of interaction between emotion and gut
      function in IBS. These psychologic therapies are intended to break the negative
      feedback loop between emotion and gut function in order to reduce symptoms.
      Attention to the psychologic issues underlying IBS helps reduce psychosocial
      factors that maintain the presence of symptoms and inappropriate health-care
      seeking behavior. There are a number of common elements in the psychologic
      approaches that can be used in routine clinical practice; these include a
      detailed assessment, psychoeducation, support, and reassurance.

PMID- 11469992
TI  - Intestinal Gas.
AB  - The most common symptoms associated with intestinal gas are excessive eructation,
      flatulence, and abdominal bloating and distention. Unfortunately, few therapies
      have been shown to be effective in treating these symptoms. Excessive eructation
      can be treated by decreasing excessive air swallowing. Bloating and gaseous
      distension can improve in some patients by avoiding foods containing partially
      digested or absorbed polysaccharides, by taking replacement enzymes (such as alfa
      galactosidase or lactase), or by taking antibiotics directed toward altering the
      colonic flora. Activated charcoal or prokinetic agents (such as tegaserod and
      metoclopramide) also can be effective options in some patients. For noxious odor
      associated with flatus, bismuth subsalicylate or the charcoal cushion may improve
      patients' symptoms.

PMID- 11469993
TI  - Augmented Visceral Perception.
AB  - Disorders of augmented visceral perception include functional (or nonulcer)
      dyspepsia and irritable bowel syndrome (IBS). Enhancement of luminal perception
      can result from alterations in normal elastic gut wall properties or exaggerated
      responsiveness of visceral sensory nerve pathways. Standard therapies for
      functional dyspepsia are effective in subsets of patients and may act in part by
      compensating for gastric hypersensitivity (as with acid-suppressing drugs) or by
      enhancing gastric compliance (as with some motor-stimulating agents). Likewise,
      conventional treatments of patients with IBS reduce visceral perception via
      effects on sensory nerve function (fiber supplements) or luminal wall properties
      (antispasmodic drugs). Antidepressants are increasingly used in patients with
      functional dyspepsia or IBS. These drugs have several purported mechanisms,
      including 1) luminal relaxation, 2) blunting of visceral hypersensitivity, and 3)
      modulation of central nervous system pain processing pathways. The efficacy of
      available and investigational agents that act as visceral analgesics or luminal
      relaxants is an area of intense pharmaceutical research.

PMID- 11469994
TI  - Rumination.
AB  - Rumination is an unusual gastrointestinal symptom that is characterized by the
      repetitive regurgitation of gastric contents into the oropharynx. The
      regurgitation occurs very soon after a meal and tends to persist for 1 to 2
      hours. Rumination is defined by the setting in which it occurs. It is seen in
      three distinct populations: infants; individuals with psychiatric and neurologic
      disorders, particularly developmental disabilities; and adults who do not have
      overt psychiatric or neurologic disorders. The hallmark of rumination, which
      separates it from other disorders of the upper gastrointestinal tract (such as
      gastroesophageal reflux disease or cyclic vomiting syndrome), is the fact that in
      patients with rumination, the gastric contents appear in the oropharynx without
      retching or nausea. Rather, the patient makes a conscious decision on how to
      handle the regurgitated material after it presents into the oropharynx. The
      regurgitated meal usually consists of undigested or partially digested food. The
      regurgitation is effortless or at most is preceded by a sensation of belching
      immediately prior to the regurgitation itself. The management of patients with
      rumination needs to be accomplished in a highly individualized manner. Children
      with infant rumination syndrome often have symptoms related to significant
      defects in bonding with their mother. Thus, problems of mother-child bonding in
      pediatric patients with rumination syndrome should be identified and
      appropriately addressed. The management of adult patients with developmental
      disabilities or neurologic impairments who ruminate focuses mainly on behavioral
      modalities, including adversive conditioning and contingency management. The
      healthy adult who ruminates and has no evidence of neurologic or developmental
      disability is best seen as someone with a habit. Management in these patients is
      directed towards adjunctive therapies (ie, the use of proton pump inhibitors or
      H(2 )receptor antagonists to decrease acid injury to the esophagus) as well as
      identifying situations and emotions that trigger the patient's symptoms.
      Randomized controlled trials of various treatment modalities need to be
      undertaken; likewise, the evaluation strategy needed to best diagnose rumination
      is yet to be well defined. At this time, the challenge for gastroenterologists is
      to understand the nature of rumination, to identify individuals at high risk, and
      to use the management strategies most associated with good outcomes in patients
      with rumination in various clinical settings.

PMID- 11469995
TI  - Bile duct injury: new aspects of diagnosis and treatment.

PMID- 11469996
TI  - Hepatitis A vaccine interchangeability.

PMID- 11469997
TI  - Infectious complications of cirrhosis.
AB  - Infectious complications in cirrhotic patients can cause severe morbidity and
      mortality. Bacterial infections are estimated to cause up to 25% of deaths in
      cirrhotic patients. The most frequent are urinary tract infection, spontaneous
      bacterial peritonitis, respiratory tract infection, and bacteremia. It has been
      said that cirrhosis is the most common form of acquired immunodeficiency,
      exceeding even AIDS. The specific risk factors for infection in cirrhotic
      patients are low serum albumin, gastrointestinal bleeding, intensive care unit
      admission for any cause, and therapeutic endoscopy. Certain infectious agents are
      more virulent and more common in patients with liver disease. These include
      Vibrio, Campylobacter, Yersinia, Plesiomonas, Enterococcus, Aeromonas,
      Capnocytophaga, and Listeria species, as well as organisms from other species.
      Spontaneous bacterial peritonitis is a frequent, severe, life-threatening
      complication of patients with ascites. Current observations and recommendations
      regarding treatment and prophylaxis are reviewed. A brief synopsis of
      miscellaneous infections encountered in cirrhotic patients is also included.

PMID- 11469998
TI  - Gastrointestinal complications of schistosomiasis.
AB  - Schistosomiasis is an important disease in many parts of the world and has
      affected the course of human history many times over. The parasitic infection is
      acquired during contact with infected water. A chronic inflammatory response to
      schistosome eggs, mediated by both cellular and humoral mechanisms, is the root
      of the pathology seen in schistosomiasis. Hepatosplenic disease results in
      intrahepatic presinusoidal portal hypertension. The resultant esophageal and
      gastric varices are an important cause of morbidity and mortality. Standard
      treatment guidelines for managing varices can be applied to patients with
      schistosomiasis. Coinfection with viral hepatitis results in liver disease that
      progresses more rapidly and is more difficult to treat. Intestinal
      schistosomiasis may be confused with other disease states and can be an important
      cause of morbidity, especially in heavily infected patients. Diagnosis relies on
      demonstration of schistosome eggs in feces or tissue. Praziquantel is the
      treatment of choice. The development of a vaccine for schistosomiasis is an
      important goal in the attempt to control this disease.

PMID- 11469999
TI  - Diarrhea in the returned traveler.
AB  - Diarrhea in the returned traveler is a common problem that can be caused by a
      number of different pathogens. A history of the patient's travel and exposures,
      the duration of illness, the response to prior treatment, and the clinical
      syndrome can help to establish a good etiologic differential diagnosis on which
      further therapy can be based. Many of these patients can be treated empirically
      with antibiotics, either a fluoroquinolone or azithromycin, without further
      microbiologic evaluation. Those patients with severe or persistent disease or
      comorbid illnesses, or those who have failed empiric therapy, should undergo
      further microbiologic evaluation with directed stool cultures and ova and
      parasite screening. For those patients with negative evaluations, further empiric
      therapy may be warranted if syndromes are suggestive of specific agents of
      infection, such as by Giardia or Cyclospora species. Other patients may require
      endoscopic evaluation to exclude diagnoses such as tropical sprue or inflammatory
      bowel disease.

PMID- 11470000
TI  - New developments in the understanding of cholera.
AB  - Recent advances in prevention and treatment of cholera have occurred in the areas
      of vaccine testing, modifications of oral-rehydration solutions (ORS), and
      antimicrobial treatment. Oral vaccines consisting of killed whole bacterial cells
      (WC) with and without the B-subunit of cholera toxin (BS) were shown to be
      effective in large trials in Bangladesh, Peru, and Vietnam. However, the trials
      did not resolve whether two or three doses of vaccine are required and whether BS
      adds significantly to the immune protection of WC. Live, attenuated bacterial
      vaccines that are immunogenic and have been shown protective in human volunteer
      studies are candidates for future field trials. Rehydration of patients is a life
      saving effort. The best ORS contains rice powder in place of glucose, and
      solutions with reduced osmolarity (245 mOsm/L, sodium 75 mEq/L) are as effective
      as standard ORS. Ciprofloxacin in a single dose is effective in adults, and
      erythromycin or ampicillin in multiple doses is effective in children.

PMID- 11470001
TI  - A perspective on tropical sprue.
AB  - A diagnosis of tropical sprue, an infrequent affliction of inhabitants and
      travelers in tropical regions, should be considered in patients with a compatible
      history, malabsorption, and chronic diarrhea. It can occur in either endemic or
      epidemic form and can be preceded by acute gastroenteritis. The cause of tropical
      sprue is still unknown, although most data support an infectious etiology.
      Therapeutic experience is greatest with folic acid and tetracycline. Most
      patients can be expected to recover with proper nutritional support, although
      relapses and slow responses occur.

PMID- 11470002
TI  - GLP-2 and nutrient absorption.

PMID- 11470003
TI  - The role of intestinal transplantation in the management of intestinal failure.
AB  - Significantly reduced morbidity and mortality is needed before intestinal
      transplantation will be applicable in most patients with intestinal failure who
      are on long-term total parenteral nutrition (TPN). However, transplantation does
      play a role if TPN fails, with failure defined by Medicare as liver failure,
      frequent line sepsis, major central vein thrombosis, or recurrent dehydration. Of
      these complications, the relationship between liver failure and subsequent death
      in high-risk subgroups of long-term TPN patients has been shown clearly. Patients
      with less than 100 cm of postduodenal small bowel, an end-jejunostomy, no
      ileocecal valve or cecum, or persistently elevated liver function levels are at
      high risk for end-stage liver disease (ESLD). Early referral to experienced
      centers is suggested in these circumstances. High-risk patients may also take
      part in clinical trials of promising therapies to increase intestinal adaptation
      and prevent liver failure. Living donors should be considered for transplant
      candidates to minimize waiting time and optimize HLA matching. ESLD patients need
      a liver-intestine transplant. Because their waiting-list mortality is very high,
      their status on the liver waiting list should be elevated if possible. High
      incidence of early death from sepsis is reported after intestinal transplant,
      even at experienced centers. Aggressive measures should be taken if uncontrolled
      sepsis occurs, including discontinuing immunosuppression and removing the graft.
      Further research is needed in intestinal immunology and in development of
      strategies to decrease the need for aggressive immunosuppression in these
      transplant recipients. The ultimate role of intestinal transplantation will be
      determined by its capacity to show superiority, both in effectiveness and safety,
      to long-term TPN.

PMID- 11470004
TI  - Probiotics and functional foods in gastrointestinal disorders.
AB  - Probiotics are live microbial food supplements that benefit the host animal by
      improving intestinal microbial balance. When they are fed in yogurts, they can
      fall into the category of functional foods. Functional foods include these
      probiotics, prebiotics, and, to a certain extent, dietary fiber. Prebiotics are
      nondigestible food ingredients or supplements that alter the intestinal flora and
      stimulate the growth of healthy bacteria. Dietary fibers are part of plant foods
      that are nonstarch polysaccharides and are poorly digested or not digested by
      human enzymes. The physiologic process in which probiotics and functional foods
      affect the intestinal flora is through the balance of the intestinal
      microecology. This review looks at the four major components of intestinal
      microecology and describes the probiotics in use today and their clinical
      relevance. Although probiotics hold great promise and appear to be useful in some
      settings, more clinical study is needed to firmly establish the relevance of
      probiotic therapy.

PMID- 11470005
TI  - Gastrointestinal food allergies: do they exist?
AB  - Gastrointestinal (GI) symptoms are often attributed to adverse reactions to foods
      (ARF), but it is not always clear whether such reactions are caused by food
      allergy. A reaction to food proteins that is mediated by immunologic events is
      referred to as food allergy or food hypersensitivity. One of the most common
      types of food allergy is the IgE-mediated immediate hypersensitivity reaction to
      foods, which can give rise to dermatologic and respiratory tract symptoms in
      addition to GI complaints. Other GI forms of food allergy include food protein
      induced enterocolitis or gastroenteropathy, celiac disease, and some cases of
      eosinophilic gastroenteritis. Because most patients complaining of adverse
      reactions to food have non-immune mechanisms for their complaints, it is
      important to distinguish the various types of ARF, as their management may differ
      substantially. Recent advances in the field of food allergy provide opportunities
      to improve diagnostic methods and develop new modalities for management that will
      complement the current practice of allergen avoidance.

PMID- 11470006
TI  - Dietary fat intake and inflammatory bowel disease.
AB  - The biologic role of fatty acids as immunomodulators has been extensively studied
      in the in vitro and experimental setting because of its potential therapeutic
      applications in chronic immune-based diseases. Unlike the conventional treatments
      for such conditions, this approach seldom produces severe side effects. The
      possibility of manipulating dietary fat as a treatment of inflammatory bowel
      disease (IBD) has been explored for a number of years. However, to date, few
      epidemiologic and experimental studies support the potential use of dietary fatty
      acid modification. Most of the attempts to demonstrate the usefulness of this
      therapeutic approach in clinical studies for both active and maintenance
      treatment in IBD have not succeeded. This lack of success is due in the majority
      of cases to defects in study design and the use of inappropriate "placebo"
      substances. This review analyzes the potential role of manipulating dietary fatty
      acids in IBD with respect to disease treatment and as a possible public health
      tool. Also discussed is the fact that fat sources may be at least as important as
      the individual fatty acids because of their non-fatty acid components.

PMID- 11470008
TI  - Salt and blood pressure: What's new?

PMID- 11470007
TI  - Nutrition in hepatic failure and liver transplantation.
AB  - Protein-energy malnutrition (PEM) is a common problem in patients with end-stage
      liver disease, and it is universally present in patients undergoing orthotopic
      liver transplantation. Although PEM is an independent risk factor for morbidity
      and mortality, it need not be considered an absolute contraindication for liver
      transplantation. The etiology of PEM in liver disease is multifactorial and
      includes decreased nutrient and calorie intake, alterations in intestinal
      malabsorption and/or maldigestion, and diverse abnormalities of carbohydrate,
      fat, and protein metabolism. This article reviews the prevalence of malnutrition,
      its pathophysiology, different modalities for assessment of body composition, and
      general guidelines for nutritional support in patients with liver disease and
      liver transplantation.

PMID- 11470009
TI  - Clinical trials report. When can treatment of hypertension be stopped?

PMID- 11470010
TI  - Statins and blood pressure regulation.
AB  - Hypertension and high serum cholesterol levels are two of the most relevant risk
      factors for cardiovascular diseases. A combined increase in both risk factors has
      been reported in a significant proportion of patients with coronary artery
      disease. Statins are the most widely used drugs to treat hypercholesterolemia,
      and they interact with blood pressure control in different populations of
      hypertensive patients. A significant reduction in blood pressure associated with
      the use of statins has been described in patients with untreated hypertension and
      in patients treated with antihypertensive drugs, particularly angiotensin
      converting enzyme inhibitors and calcium channel blockers. The effect of statins
      on blood pressure control has also been reported in diabetic patients. The
      mechanisms responsible for the hypotensive effect seem to be largely independent
      of the effect of statins on lipid profile, and are probably related to their
      interaction with endothelial function or angiotensin II receptors. The capacity
      of statins to improve blood pressure control could be a useful consideration for
      an integrated approach to better prevention of cardiovascular diseases.

PMID- 11470011
TI  - The INSIGHT and NORDIL trials: Are calcium antagonists equivalent to established
      drug therapies for cardiovascular protection?
AB  - Calcium channel blockers have come into worldwide use for treating hypertension
      and other circulatory disorders. In recent years, results of several
      observational studies have suggested that these drugs may not be as safe or
      effective as other available therapies, such as diuretics and beta-blockers, in
      the prevention of cardiovascular events. The Nordic Diltiazem (NORDIL) and the
      International Nifedipine GITS Study: Intervention as a Goal in Hypertension
      Treatment (INSIGHT) studies were the first two randomized interventional trials
      in hypertensive patients that directly compared the effects of therapy based on
      calcium antagonists with those of diuretic and beta-blocker-based treatment on
      major cardiovascular endpoints. Both studies found that the effectiveness of
      calcium antagonist therapy was similar to that of diuretic and beta-blocker
      therapy for preventing the composite primary endpoint of fatal and nonfatal
      stroke, myocardial infarction, and other cardiovascular death. The two studies
      shared several nonsignificant trends for cause-specific events, including greater
      stroke prevention and lesser coronary event prevention in the calcium antagonist
      groups compared with the diuretic and beta-blocker groups. There is not yet
      sufficient evidence to prove whether cause-specific differences exist. Results of
      the NORDIL and INSIGHT studies support incorporating calcium antagonist-based
      therapy as an additional safe and effective approach for preventing blood
      pressure-related illness and death.

PMID- 11470012
TI  - The effect of antihypertensive drugs on vascular compliance.
AB  - Measurement of vascular compliance has assumed increasing importance as a marker
      of early disease of the vascular wall, a predictor of future vascular disease,
      and a way to monitor the effects of vasoactive agents on arterial wall stiffness.
      Vascular compliance can be estimated by several methods: measurement of the pulse
      pressure, or pulse pressure-stroke volume ratio; analysis of the systolic pulse
      wave augmentation index and the diastolic pulse wave contour; ultrasonic echo
      tracking; and MRI. Because few comparative studies have been done, the
      physiologic significance of the measures of compliance obtained by each method is
      uncertain. Antihypertensive drugs may improve vascular compliance by reducing
      blood pressure, relaxing vascular smooth muscle, or promoting long-term effects
      on vascular smooth muscle and cardiomyocyte growth and remodeling. Angiotensin
      converting enzyme (ACE) inhibitors have been reported to improve vascular
      compliance in nearly all studies, suggesting a beneficial class effect
      independent of blood pressure reduction. Favorable changes in the vascular wall
      lumen ratio of small vessels from subcutaneous gluteal biopsy specimens after
      treatment with ACE inhibitors and the persistence of improved vascular compliance
      after withdrawal of therapy indicate that these agents may produce long-term
      vascular remodeling. Although few studies have been done, angiotensin II receptor
      antagonists improve vascular compliance, possibly by blocking angiotensin II
      mediated cell proliferation and increasing apoptosis via unopposed AT1 receptor
      stimulation. In contrast, calcium antagonists and beta-blockers have variable
      effects on vascular compliance, although beta-blockers with intrinsic
      sympathomimetic activity improve vascular compliance. Diuretics have little
      effect on vascular compliance beyond their blood pressure-lowering actions,
      except for spironolactone, which by improving vascular compliance may have
      contributed to the reduction in heart failure mortality seen in the Randomized
      Aldactone Evaluation Study.

PMID- 11470013
TI  - Do most antihypertensive agents have a sympatholytic action?
AB  - The sympathetic nervous system is a major modulator of cardiovascular functions.
      Over the past three decades, numerous studies, using various methodologies, have
      reported the existence of a variety of pre- and postsynaptic sympathetic
      dysfunctions in essential hypertension. Most of those abnormalities facilitate
      sympathetic neurotransmission, resulting in a chronic increase in the sympathetic
      tone and reactivity in an important proportion of hypertensive patients. The
      chronic sympathetic activation is also associated with major alterations in the
      balance between postsynaptic adrenergic receptors in cardiovascular tissues.
      Indeed, an attenuation of beta-adrenergic functions and a potentiation of alpha1
      adrenergic functions have been demonstrated in human cardiovascular tissues,
      suggesting the development of a sympathetic postsynaptic alpha1 dominance during
      the development and evolution of hypertension. The chronic activation of the
      sympathetic system is deleterious and could contribute to the development of most
      cardiovascular complications associated with hypertension. One of the major aims
      of antihypertensive therapy should be to attenuate pre- or postsynaptic
      sympathetic tone. Most antihypertensive drugs have been found to improve either
      pre- or postsynaptic sympathetic functions in hypertensive patients. At the
      presynaptic level, the effects of antihypertensive drugs have been found to be
      more variable. At the postsynaptic level, all currently used antihypertensive
      drugs have been found to attenuate alpha1-adrenergic functions either by
      interfering directly with intracellular mechanisms underlying alpha1-adrenergic
      functions or indirectly by decreasing the release of norepinephrine from
      peripheral sympathetic nerves.

PMID- 11470014
TI  - Central sympathoinhibitory effects of calcium channel blockers.
AB  - It is generally assumed that the arterial vasodilation induced by inhibition of
      Ca(2+) influx into vascular smooth muscle cells represents the main mechanism for
      the hypotensive effect of dihydropyridine calcium channel blockers. Increases in
      sympathetic tone have been related to activation of the arterial baroreflex by
      rapid lowering of blood pressure. This review highlights new findings in two
      areas. First, in animal studies, direct central administration of
      dihydropyridines such as nifedipine or amlodipine lowers sympathetic nerve
      activity and thereby blood pressure. Peripheral administration of nifedipine or
      amlodipine at low rates appears to result in gradual accumulation of drug in the
      central nervous system, and also causes lowering of sympathetic nerve activity
      and thereby lowering of blood pressure (rather than by arterial vasodilation).
      Second, in hypertensive humans treated with long-acting dihydropyridines and
      presumably little activation of the arterial baroreflex, some studies have
      demonstrated lowering of sympathetic activity (as assessed by plasma
      norepinephrine), but others reported increases (as assessed by plasma
      norepinephrine or microneurography). This sympathoexcitatory response may be due
      to activation of the renin-angiotensin system, particularly at higher doses.

PMID- 11470016
TI  - The benefit of treating isolated systolic hypertension.
AB  - Isolated systolic hypertension affects over 15% of all people older than 60 years
      of age. In the elderly, systolic hypertension is a major modifiable
      cardiovascular risk factor. Systolic blood pressure is associated with higher
      risk of an adverse outcome. Diastolic blood pressure is inversely correlated with
      total mortality, independent of systolic blood pressure, highlighting the role of
      pulse pressure as risk factor. Three placebo-controlled outcome trials on
      antihypertensive drug treatment in older patients with isolated systolic
      hypertension have been published: the Systolic Hypertension in the Elderly
      Program (SHEP), the Systolic Hypertension in Europe (Syst-Eur) Trial, and the
      Systolic Hypertension in China (Syst-China) Trial. These three trials showed the
      benefit of antihypertensive drug treatment. A meta-analysis was done by pooling
      the patients from these three trials with a subset of patients with isolated
      systolic hypertension from five other trials in the elderly. The pooled results
      of 15,693 older patients with isolated systolic hypertension prove that
      antihypertensive drug treatment is justified if systolic blood pressure on
      repeated clinic measurements is 160 mm Hg or higher.

PMID- 11470015
TI  - The therapeutic potential of endothelin receptor antagonists in cardiovascular
      disease.
AB  - Endothelin (ET)-1, a 21-amino acid peptide, is the predominant isoform of the
      endothelin peptide family. ET-1 is ubiquitously expressed and stimulates
      vasoconstriction and cell proliferation. Enzymes such as endothelin converting
      enzymes (ECE), chymases, and non-ECE metalloproteinases contribute to the
      synthesis of ET-1, which is regulated in an autocrine fashion in vascular and
      nonvascular cells. Endothelin ET(A) receptors mediate vasoconstriction and cell
      proliferation, whereas ET(B) receptors are involved in the clearance of ET-1,
      inhibition of endothelial apoptosis, release of nitric oxide and prostacyclin,
      and inhibition of ECE-1 expression. Most cardiovascular diseases, such as
      arterial hypertension, atherosclerosis, restenosis, heart failure, idiopathic
      cardiomyopathy, pulmonary hypertension, and renal failure are associated with
      local activation of the endothelin system. Experimental studies and first
      clinical trials suggest that ET-1 is importantly involved in the functional and
      structural changes in the cardiovascular system, and that many of the actions of
      ET-1 are mediated through pressure-independent mechanisms. Endothelin antagonists
      promise to be successful as a new class of drugs for the treatment of
      cardiovascular diseases.

PMID- 11470017
TI  - Prospectively designed overviews of recent trials comparing antihypertensive
      regimens based on different drug classes.
AB  - Randomized trials have provided clear evidence of the beneficial effects of many
      different blood pressure-lowering regimens compared with placebo. The comparative
      effects of antihypertensive regimens based on different drug classes are less
      well established. The Blood Pressure Lowering Treatment Trialists' Collaboration
      conducted a series of prospectively designed overviews of randomized trials that
      compared the effects of different drug classes on major cause-specific outcomes.
      These overviews found no differences between the effects of regimens based on
      angiotensin converting enzyme inhibitors and those based on diuretics or b
      blockers. There was limited evidence of small differences between regimens based
      on calcium antagonists and those based on diuretics or beta-blockers. The
      overviews of regimens based on calcium antagonists compared with those based on
      angiotensin converting enzyme inhibitors recorded too few events to provide
      reliable findings. Over the next few years, the findings of ongoing trials and
      future cycles of overview analyses conducted by the Collaboration should
      substantially add to these data.

PMID- 11470018
TI  - The antiatherogenic effects of antihypertensive treatment: trials completed and
      ongoing.
AB  - B-mode ultrasonography provides a reliable means of measuring carotid artery wall
      intima-media thickness. Because carotid intima-media thickness is correlated with
      blood pressure and is predictive of future cardiovascular events, it can be used
      as an endpoint in intervention trials. Inclusion of carotid bifurcation in the
      measurements appears necessary for inferences about atherosclerosis. Several
      intervention studies using antihypertensive agents have been completed and others
      are ongoing. Placebo-controlled studies have shown beneficial effects of calcium
      antagonists and beta-blockers, and contradictory responses with angiotensin
      converting enzyme inhibitors, but none of these studies have been performed in
      hypertensive patients. In hypertensive patients, three studies comparing
      different antihypertensive agents have been completed, with some evidence
      favoring calcium antagonists over diuretics. Two studies are ongoing, and should
      be completed and published soon.

PMID- 11470019
TI  - Lessons learned from prematurely terminated clinical trials.
AB  - Controlled clinical trials in cardiovascular disease are the cornerstone for
      therapeutic advances in this field of medicine. Since the introduction of the
      concept of controlled clinical trials, there has been substantial progress in the
      design, conduct, and analysis of such studies. A growing awareness of ethical
      issues emerging from such trials has led to increased public and investigator
      scrutiny, and the routine requirement for interim data analysis. A benefit of
      such interim analysis is that either an entire clinical trial or a specific
      treatment limb can be stopped if the observed findings warrant premature
      termination. For example, highly positive findings, as were noted in the Heart
      Outcomes Prevention Evaluation (HOPE) study, led to its closure about 1 year
      early after 4.5 years of treatment. Alternatively, the doxazosin treatment limb
      of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
      Trial (ALLHAT) and the amlodipine treatment limb of the African-American Study of
      Kidney Disease and Hypertension (AASK) were stopped early because of negative
      findings. Finally, economic considerations can enter into the decision to close a
      study early as was the case in the Controlled ONset Verapamil INvestigation of
      Cardiovascular Endpoints (CONVINCE) trial. Most such decisions rely heavily on
      information obtained from independent data and safety monitoring boards. Such
      boards ensure patient safety by providing an unbiased ongoing review of data,
      which would otherwise be unavailable until a study's completion. Early
      termination of a clinical trial can have important clinical implications and, in
      particular, can redirect patterns of clinical practice.

PMID- 11470020
TI  - Tailoring Antibiotic Treatment to Host Immune Status: The Host, Not the Drug,
      Determines Outcome.

PMID- 11470021
TI  - Outpatient Management of Infective Endocarditis.
AB  - Because of unique host defense characteristics of the endocardium, successful
      therapy for infective endocarditis (IE) has necessitated bactericidal
      antimicrobial agents, generally administered in high doses for prolonged periods
      of time. This has required therapy in the hospital setting. However, in recent
      years, it has become apparent that outpatient therapy is feasible if appropriate
      agents can be administered at home, for example, using either home parenteral
      therapy or oral preparations. Over the past few decades, there has been a trend
      toward reducing inpatient reimbursement for various conditions, including serious
      infections. The decision to treat IE on an outpatient basis is made more easily
      if based on previous published experience. Published reports have concluded that
      outpatient therapy is more appropriate for "uncomplicated" IE caused by
      relatively susceptible microorganisms. The purpose of this paper is to review
      data describing the results of management of IE in the outpatient setting.

PMID- 11470022
TI  - Differentiation Between Infection and Rejection in the Management of Cardiac
      Transplant Patients.
AB  - Infections commonly complicate cardiac transplantation, and the clinical
      presentation of post-transplantation infection is usually readily distinguishable
      from that of rejection. Infection of the allograft may mimic rejection, however,
      and endomyocardial biopsies are required to distinguish these two entities.
      Cytomegalovirus is the most common cause of post-transplant cardiac infection.
      Although there are noninvasive studies that may suggest a diagnosis of
      cytomegalovirus infection, the noninvasive diagnosis of infection-related
      myocarditis remains challenging.

PMID- 11470023
TI  - Changing Risk Factors for Pediatric Infective Endocarditis.
AB  - Infective endocarditis in children is an uncommon infection. Three major groups
      of children are at risk: 1) those with underlying congenital heart disease, 2)
      those with central vascular catheters, and 3) children infected with certain
      virulent organisms. Although the overall incidence of infective endocarditis has
      increased, the population of children involved has changed. Children with
      corrected congenital heart disease are at risk during the early postoperative
      period. Children in whom vascular shunts or grafts are employed remain at the
      highest risk for endocarditis. Use of central vascular catheters increases risk
      in children with underlying heart disease and those with normal hearts. Finally,
      certain pathogens attack the heart valves and cause high morbidity and mortality.

PMID- 11470024
TI  - Contemporary Approaches to the Management of Neurosurgical Complications of
      Infective Endocarditis.
AB  - Infective endocarditis can often involve the nervous system, resulting in stroke,
      intracerebral hemorrhage, infectious aneurysm formation, cerebral abscess, and
      spinal epidural infection. Many of these problems require neurosurgical
      attention. Modern advances in neuro- surgical critical care, computerization,
      instrumentation, and radiologic imaging have affected the treatments available to
      patients with neurosurgical manifestations of infective endocarditis. This paper
      is a brief overview of the contemporary management of neurosurgical complications
      of infective endocarditis.

PMID- 11470025
TI  - Clinical Trials Report.

PMID- 11470026
TI  - Progressive Multifocal Leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy is a subacute demyelinating disease
      that occurs in patients with defects in cell-mediated immunity, including those
      with AIDS and lymphoproliferative disorders. It is caused by reactivation of JC
      virus (JCV), which infects 70% to 90% of the population by adulthood, but remains
      latent in normal hosts. Once reactivated, JCV infects oligodendrocytes and
      astrocytes, with resultant cell lysis, leading to focal areas of demyelination
      and necrosis in cerebral white matter causing focal neurologic deficits and
      characteristic findings on MRI. Polymerase chain reaction for the detection of
      JCV is a sensitive and specific test, replacing brain biopsy as the initial
      diagnostic test in the appropriate clinical setting. Historically, the prognosis
      of progressive multifocal leukoencephalopathy is poor, with most patients dying
      within 6 months of diagnosis. Antiviral medications targeted against JCV have
      shown little success. However, with the use of highly active antiretroviral
      therapy, survival of AIDS patients with progressive multifocal
      leukoencephalopathy has improved.

PMID- 11470027
TI  - Timing of Administration of Antimicrobial Therapy in Bacterial Meningitis.
AB  - Bacterial meningitis is an important cause of morbidity and mortality in the
      United States and throughout the world. The diagnosis of bacterial meningitis is
      often delayed in patients as a result of numerous factors such as length of
      illness, use of radiologic imaging studies, and/or prior use of antimicrobial
      agents. Many textbooks emphasize the need for prompt initiation of antimicrobial
      therapy in a patient with suspected acute bacterial meningitis to prevent many of
      the long-term sequelae associated with this disorder. We have reviewed the
      literature to determine if there is a standard of care for timing of
      administration of antimicrobial therapy in patients with a diagnosis of acute
      bacterial meningitis. Although the clinical data are inconclusive, it makes
      intuitive sense to initiate antimicrobial therapy as soon as possible in any
      patient with suspected or proven bacterial meningitis before the patient's
      illness advances to a high level of clinical severity, beyond which antimicrobial
      therapy is less likely to be of benefit. However, clinical experiences suggest
      that patient outcome in bacterial meningitis is a result of multiple factors,
      since some patients treated within a few hours of symptoms develop an adverse
      outcome whereas others who are symptomatic for days prior to presentation suffer
      no adverse sequelae.

PMID- 11470028
TI  - Therapy of Cryptococcal Meningitis in non-HIV-infected Patients.
AB  - Cryptococcus neoformans is the most common cause of fungal meningitis in HIV and
      non-HIV-infected patients. The organism has a worldwide distribution, with cases
      typically occurring among patients with well-recognized specific underlying
      disorders associated with dysfunction of cell- mediated immunity. While the
      therapy for disease was studied extensively in the 1970s and the 1980s among non
      HIV-infected individuals, most of the recently published data have concerned
      therapy for central nervous system cryptococcosis in HIV-infected patients. As a
      result, the current approach to therapy for central nervous system cryptococcosis
      in the non-HIV-infected patient represents a hybrid of the established "gold
      standard," which includes at least 6 weeks of combination therapy with
      amphotericin B and 5-flucytosine, and the more contemporary regimen, which
      consists of 2 weeks of induction therapy with an amphotericin B-containing
      regimen followed by fluconazole. Clearly, well-designed prospective studies are
      needed to define the best approach to therapy in these patients, but until then,
      we must rely on the results of the existing clinical trials and carefully
      interpret the results of the available retrospective data. At present,
      amphotericin B (deoxycholate or lipid-associated) is recommended as initial
      therapy for all non-HIV-infected patients with proven or suspected cryptococcal
      meningitis. Fluconazole plays an important role in consolidation therapy and
      among selected patients who require long-term chronic suppression. The potential
      role of the newer triazoles (voriconazole and posaconazole) is undetermined.

PMID- 11470029
TI  - Therapy and Prevention of Cytomegalovirus Retinitis.
AB  - Highly active antiretroviral therapy (HAART) has redefined the natural history of
      cytomegalovirus (CMV) retinitis. Once a major cause of blindness in AIDS
      patients, its incidence has plummeted and its clinical course has been altered.
      The potential of HAART for immunologic restoration should guide treatment
      decisions, and may ultimately lead to the possibility of withdrawal from
      maintenance anti-CMV therapy. However, new cases of CMV retinitis have begun to
      emerge in virologic and immunologic failures to HAART. The impact of HAART
      continues to evolve with the discovery of sight-threatening immune recovery
      uveitis. Specific anti-CMV treatment strategies have expanded and improved to
      include therapeutic options not requiring the parenteral route of administration
      such as valganciclovir, which has enhanced oral bioavailability.

PMID- 11470030
TI  - Clinical Pharmacologic Considerations for HIV-1 Protease Inhibitors.
AB  - Many data associate low protease inhibitor plasma concentrations with suboptimal
      virologic responses, whereas relatively few data associate high plasma
      concentrations with increased likelihood of toxicity. Knowledge of relationships
      between concentrations and virologic response is important because significant
      variability in plasma concentrations exists among HIV-infected persons.
      Unfortunately, a prospectively confirmed therapeutic range that reduces the risk
      of virologic failure has not been established for the protease inhibitors. Recent
      investigations have identified a relationship between the measured minimum plasma
      concentration, the in vitro susceptibility of the subject's virus, and virologic
      outcome. However, differences in virologic response may further depend on other
      pharmacologic factors such as protein binding, intracellular kinetics, expression
      of drug transporters, and drug synergies or antagonisms. In the future, dosing
      strategies that accommodate the variability in both pharmacokinetics and
      pharmacodynamics may improve virologic outcomes. In summary, clinical
      pharmacologic considerations for protease inhibitors can be used to promote their
      optimal use.

PMID- 11470031
TI  - Perinatal Transmission of HIV: Recognition and Treatment Interventions.
AB  - Great strides have been made in the fight against vertical transmission of HIV-1.
      Improved understanding of mechanisms and timing of transmission of HIV-1 from
      mother to child have led to the development of effective intervention strategies
      that have reduced transmission rates to unprecedented low levels, below 2% in
      developed countries. New reports using shortened, more affordable courses of
      antiretrovirals prenatally or at the time of delivery have also shown a
      significant reduction in transmission, over 50% in studies conducted in the
      developing world. These advances, combined with ongoing studies using simplified
      effective treatment regimens, have made possible the potential to significantly
      reduce perinatal transmission worldwide. Future challenges include reduction of
      breast feeding transmission and the development of an effective HIV-1 vaccine to
      produce long-lasting protection.

PMID- 11470032
TI  - Childhood anxiety disorders: etiology, assessment, and treatment in the new
      millennium.
AB  - The following article reviews the literature on childhood anxiety disorders
      published during the past year. Publication trajectories suggest ever increasing
      empirical focus on the nature, developmental influences, assessment, and
      treatment of anxiety in children. The past year witnessed significant events on a
      national level with respect to public policy development. Despite such forward
      progress, research on childhood anxiety remains disproportionally behind that of
      the disruptive behavior disorders. With respect to treatment, cognitive
      behavioral approaches have demonstrated strong empirical support. Although there
      is limited data yet available, selective serotonin reuptake inhibitors appear to
      be efficacious in treating anxiety in children.

PMID- 11470033
TI  - Social anxiety disorder: recent findings in the areas of epidemiology, etiology,
      and treatment.
AB  - Social anxiety disorder is a common and chronic disorder that leads to
      substantial psychosocial impairment. The disorder occurs early in childhood, and
      is frequently comorbid with a variety of other psychiatric diagnoses like
      depression, other anxiety disorders, substance abuse, and eating disorders. Given
      these serious implications of social anxiety disorder, early effective treatment
      is extremely important. Pharmacotherapy, with a selective serotonin reuptake
      inhibitor, and cognitive behavioral therapy are the first choice of treatments
      for social anxiety disorder. This paper reviews recent findings on the
      epidemiology, etiology, and treatment for social anxiety disorder, and highlights
      areas where future research should be directed.

PMID- 11470034
TI  - The psychobiology of obsessive-compulsive disorder: how important is the role of
      disgust?
AB  - Psychobiologic models of obsessive-compulsive disorder (OCD) have focused on
      cortico-striatal-thalamic-cortical (CTSC) circuits, noting normal function in
      cognitive and motoric procedural strategies. Such models have relied on the
      classification of OCD as an anxiety disorder, seldom exploring other relevant
      emotions. Based on the hypothesis that a central emotion in OCD is disgust, the
      authors review the literature on its psychobiology and its relevance to current
      models of OCD. There are important parallels between the psychobiology of OCD and
      that of disgust. Obsessive- compulsive disorder may be conceptualized in terms of
      a false contamination alarm in which disgust plays a crucial organizing or
      embodying role, not only at a basic brain level, but also in terms of the
      psychosocial aspects of the disorder. Just as psychobiologic models of panic
      disorder and post- traumatic stress disorder have been strengthened by the
      inclusion of preclinical work on amygdala-mediated fear conditioning, so findings
      on disgust and its mediating CSTC circuits may generate useful hypotheses for OCD
      research.

PMID- 11470035
TI  - Post-traumatic stress disorder: a review of recent findings.
AB  - This article provides an update on recent findings in post-traumatic stress
      disorder (PTSD) with reference to pertinent epidemiologic, etiologic, diagnostic,
      and treatment advances in the past year. New studies serve to confirm high
      prevalence rates in the general population (7% to 12%), and high rates of
      secondary mood, anxiety, and substance use disorders. Recent substantive evidence
      has highlighted 1) the unique pattern of biological alteration in PTSD that
      distinguishes it from the normative stress response, and 2) the role of
      constitutional risk factors and trauma-related factors in determining disease
      expression after trauma exposure. The emergence of consistent data suggesting
      that medications (selective serotonin reuptake inhibitors) and psychotherapies
      (cognitive-behavior therapy) are effective in reducing core symptoms and
      improving quality of life, has reinforced optimism and more widespread use of
      these interventions in patients with PTSD.

PMID- 11470036
TI  - Panic disorder.
AB  - In this article, the authors review the most recent advances in the
      pharmacotherapy, psychotherapy, and combined therapy for panic disorder. The
      authors focus on peer-reviewed data and on pragmatic clinical approaches that may
      help patients suffering from panic disorder.

PMID- 11470037
TI  - Anxiety disorders in older adults.
AB  - In the population of older adults, anxiety disorders are underdiagnosed and
      undertreated. Epidemiologic studies have generally found that the prevalence of
      anxiety disorders declines with age. Recognition of anxiety disorders in older
      adults is, however, complicated by several age-related factors including the
      presence of depression, cognitive impairment, and physical illness. A variety of
      medications have been used to treat anxiety disorders across the life span;
      however, few studies have evaluated their use specifically in older adults.
      Choice of medication requires consideration of the effects of aging on safety,
      tolerability, and adherence. Available data suggest that cognitive and behavioral
      treatments may be effective for anxiety disorders in older adults. Appropriate
      medical evaluation and psychosocial interventions are recommended prior to
      initiating pharmacotherapy. When pharmacologic treatment is warranted,
      antidepressant medications at low doses may be useful for late-life anxiety
      disorders; other agents may be considered for augmentation or second-line use in
      certain types of patients.

PMID- 11470038
TI  - Psychotic manifestations of alcoholism.
AB  - The psychotic manifestations of alcohol physical and psychiatric disorders have
      been documented for many centuries; however, the distinction of the various
      disorders remains less well defined. Individuals often have comorbid elements of
      several disorders, and the psychotic phenomenon are often diverse. The psychotic
      manifestations of alcohol withdrawal, delirium tremens, alcohol hallucinosis,
      Wernicke's-Korsakoff's psychosis, alcohol pellagra and hepatic encephalopathy,
      Marchiafava-Bignami, central pontine myelinosis, and alcohol dementia are
      discussed in this article.

PMID- 11470039
TI  - Organic psychosis: Insight into the biology of psychosis.
AB  - Psychotic symptoms--delusions, delusional misidentifications and hallucinations-
      are observed in a variety of organic or nonorganic conditions, and are,
      therefore, diagnostically nonspecific. Common patholophysiologic denominators of
      different organic diseases may offer insights into the origin of psychotic
      symptoms. This article reviews some of the clinical and neuroimaging findings in
      organic psychoses present in various organic disorders. It attempts to extract a
      number of hypotheses about underlying biologic factors contributing to the
      development of psychotic symptoms of organic origin.

PMID- 11470040
TI  - Classification of nonschizophrenic psychotic disorders: a historical perspective.
AB  - The existence of a group of psychoses that are symptomatologically and
      prognostically different from schizophrenia and affective psychotic disorders is
      supported by clinical and epidemiologic evidence. Although such "atypical"
      psychoses account for up to 10% of all psychotic disorders, their aetiology,
      pathophysiology, and neuropathology remain insufficiently understood. Moreover,
      they have been described by different schools of psychiatry a variety of ways,
      including non-process schizophrenia, schizophreniform psychosis, reactive (or
      psychogenic) psychosis, bouffees delirantes, and cycloid psychoses, but the
      extent to which these diagnostic categories overlap or differ has not been
      systematically explored. Neither Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV), nor International Classification of Disease,
      Tenth Revision (ICD-10), provides adequate diagnostic criteria and classificatory
      categories for this group of disorders. Special attention to the refinement of
      the diagnosis and classification of the acute and transient psychotic disorders
      in future versions of the two classifications will be warranted.

PMID- 11470041
TI  - The common genetic liability between schizophrenia and bipolar disorder: a
      review.
AB  - Current psychiatric nosology, strongly influenced by Kraepelin's dichotomy,
      classifies schizophrenia and bipolar disorder as separate diagnostic categories.
      However, growing evidence indicates that the two disorders may be more closely
      related than was thought in the past. Bipolar disorder and schizophrenia display
      considerable overlap in epidemiologic features; no risk factor is known to be
      specific to either. Furthermore, family studies reveal familial co-aggregation of
      the two disorders, and twin studies suggest a significant overlap in the genes
      contributing to schizophrenia, schizoaffective disorder, and mania. Finally,
      despite the difficulties in the identification of convincing genetic loci for
      psychiatric disorders, there are at least four genomic regions in which linkage
      has been shown for both schizophrenia and bipolar disorder. Thus, recent evidence
      increasingly supports a dimensional approach in the understanding of the
      functional psychoses, and this is expected to have implications for etiologic
      research and future clinical treatment.

PMID- 11470042
TI  - Reactive psychosis and other brief psychotic episodes.
AB  - Modern classification systems have ignored the reactive psychoses, and little has
      been published using this concept during the last years. Nevertheless, the term
      is of interest in clinical practice where its presence is dependent on clinical
      skills and empathy. It is also important for a general understanding of the
      development of psychosis. The delineation from other acute psychoses needs
      clarification. Studies on reliability and validity are promising, but need
      extension. Traditionally, the concept of reactive psychosis has hardly been used
      outside Scandinavia, and it is encouraging that interest in brief psychoses seems
      growing in other cultures as well.

PMID- 11470043
TI  - Appropriate management of antiphospholipid-related pregnancy in women without
      lupus who have low titer autoantibodies.

PMID- 11470044
TI  - The epidemiology of the antiphospholipid syndrome: who is at risk?
AB  - Arterial and venous thrombosis are the most common and clinically relevant events
      of the so-called antiphospholipid syndrome; they are reported in approximately
      one third of patients with the antiphospholipid (aPL) antibodies. APL antibodies
      are part of a wide family of immunoglobulins directed against proteins complexed
      with negatively charged phospholipids. They include lupus anticoagulants (LA),
      anticardiolipin (aCL) antibodies, and the most recently recognized anti-beta-2
      glycoprotein I (beta 2-GPI) and antiprothrombin (aPT) antibodies. Previous
      thrombotic events and the presence of LA, particularly if identified by the
      dilute Russell viper venom test, appear to be the strongest risk factors for
      vascular complications. High-titer aCL antibodies have been reported to be
      associated with an increased thrombotic tendency, but this was not confirmed in
      all studies. The data only partially support the concept that anti-beta 2-GPI and
      aPT antibodies may be considered as independent risk factors for thrombosis.
      Further prospective studies are required.

PMID- 11470045
TI  - The antiphospholipid syndrome and infection.
AB  - Infectious agents have been implicated in the induction of antiphospholipid (aPL)
      antibodies and the development of the antiphospholipid syndrome (APS). This
      review focuses on the types of aPL antibodies detected in infections and
      addresses whether these antibodies are of clinical importance in patients with
      infections. Hepatitis C virus (HCV) infection is given special attention because
      this virus has the propensity to induce various autoimmune phenomena. Several
      aspects are emphasized that should be considered carefully when interpreting
      results. Most of the published data agree that thrombophilia is not observed in
      patients with infections (including HCV) because aPL antibodies are mostly the
      natural or nonpathogenic type. Thus, we do not recommend routinely testing for
      HCV in patients with APS. However, not all infection-associated aPL antibodies
      are cofactor independent. For instance, infections are increasingly recognized as
      a major precipitating condition of the catastrophic variant of APS, perhaps via
      mechanisms of molecular mimicry. Therefore, it may be possible to prevent this
      devastating evolution if the infectious process is promptly recognized and
      exhaustively treated.

PMID- 11470046
TI  - Neurologic manifestations of the antiphospholipid syndrome.
AB  - Neurologic disorders are among the most prominent clinical manifestations
      associated with the antiphospholipid syndrome. Such neurologic disorders are
      predominantly related to focal central nervous system thrombo-occlusive events.
      This review summarizes the latest data regarding the clinical aspects of stroke
      and other neurologic manifestations associated with antiphospholipid antibodies.

PMID- 11470048
TI  - Neuroimaging techniques in the diagnostic work-up of patients with the
      antiphospholipid syndrome.
AB  - The detection of multisystemic involvement often leads to a correct diagnosis of
      the antiphospholipid syndrome (APS), even in cases with predominant neurologic
      manifestations. However, when central nervous system deficits are isolated and
      have a relapsing-remitting or a progressive course, other conditions must be
      carefully considered. In this context, the diagnostic accuracy of conventional
      magnetic resonance imaging (MRI) is hampered by its limited pathologic
      specificity, which is one of the reasons why no or only modest correlations have
      been found between the burden of MRI-visible lesions and other clinical or
      laboratory measures of disease severity in patients with APS. Neuroimaging
      techniques with a higher pathologic specificity than conventional MRI show
      promise in achieving diagnostic confidence earlier in the course of APS and in
      better monitoring the efficacy of therapeutic interventions.

PMID- 11470047
TI  - What causes the antiphospholipid syndrome?
AB  - The antiphospholipid syndrome (APS) is characterized by unpredictable, sporadic,
      thrombotic events. The cause of the thrombosis is probably multifactorial and may
      involve disparate effects of the autoantibodies associated with the syndrome,
      which are known to interfere with various protein regulators of hemostasis. An
      integrated theory of pathogenesis that accounts for the diversity of
      autoantibodies and their effects suggests that cellular inflammation or apoptosis
      within the vasculature may lead to oxidation or turnover in phospholipid
      membranes. Thus, normally cryptic, functionally important epitopes of
      phospholipid-binding proteins are subjected to increased exposure to immune
      surveillance.

PMID- 11470049
TI  - Treatment of myositis with "lower" dose corticosteroids.

PMID- 11470050
TI  - The clinical laboratory evaluation of the patient with noninflammatory myopathy.
AB  - The investigations used to diagnose an inflammatory muscle disease include
      history and physical examination, evaluation of serum levels of enzymes derived
      from skeletal muscle, electromyography, magnetic resonance imaging, and muscle
      histology. The evaluation of patients who may have noninflammatory myopathy
      includes, but is not limited to, these methods. Additional tools that may be
      useful include measurements of additional biochemistries, the forearm ischemic
      exercise test, magnetic resonance spectroscopy, and special tests on muscle
      tissue. Reports published in the past year have improved and expanded our
      understanding of the numerous noninflammatory myopathies and how these tools can
      be used more effectively.

PMID- 11470051
TI  - The benefits and limitations of a physical training program in patients with
      inflammatory myositis.
AB  - The clinical features of inflammatory myositis are determined by the severity and
      extent of muscle weakness and systemic manifestations. The benefits and
      limitations of physical training programs and rehabilitation strategies depend on
      the clinical phase of the disease and analysis of underlying impairments
      responsible for functional limitations in the patient. Patients with early stage
      disease and severe weakness will be treated differently than patients who have
      responded to medication and are improving. Not all patients will respond to
      medications; their therapy programs will have different requirements. This
      article reviews available data on the physiologic responses to exercise in
      patients with inflammatory muscle diseases. New data support more aggressive
      approaches to progressive strengthening exercises for patients with inflammatory
      myositis.

PMID- 11470052
TI  - Apoptosis of skeletal muscle cells and the pathogenesis of myositis: a
      perspective.
AB  - Apoptosis is a genetically controlled form of cell death that occurs in many
      biologic processes including embryogenesis, immune cell development, and
      maintenance of peripheral immune tolerance. Recent studies have yielded evidence
      suggesting that apoptosis of parenchymal cells may play a role in providing self
      antigens to initiate autoimmune reactions. Skeletal muscle cells are fully
      differentiated and multinucleated. Apoptosis has been described in developing
      myoblasts and, recently, in mature myotubes. However, the involvement of
      apoptosis in skeletal muscle pathologies is unclear. This article reviews the
      available data concerning the occurrence of skeletal muscle cell apoptosis in
      selected muscle diseases. It also discusses the potential role of muscle cell
      apoptosis in the development of autoimmune diseases such as idiopathic
      inflammatory myopathies.

PMID- 11470053
TI  - Utility of magnetic resonance imaging in the evaluation of patients with
      inflammatory myopathies.
AB  - Magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (P-31
      MRS) provide unique, quantitative data that cannot be obtained from routine
      laboratory tests. MRI is the method of choice for imaging of muscle
      abnormalities. It is also a very sensitive technique for localizing
      nonhomogeneous inflammation in inflammatory myopathies such as dermatomyositis,
      juvenile dermatomyositis, amyopathic dermatomyositis, polymyositis, and inclusion
      body myositis. During treatment of inflammatory myopathies, the extent and
      severity of inflammation may decrease at varying rates, but weakness and fatigue
      remain serious clinical problems. The metabolic abnormalities detected with P-31
      MRS are more persistent and can be used for objective patient evaluation after
      the disappearance of inflammation and normalization of serum levels of muscle
      enzymes. With P-31 MRS, biochemical defects are quantitated, including low levels
      of ATP and phosphocreatine (PCr) and elevated concentrations of ADP and inorganic
      phosphate (Pi), which may all be related to weakness and fatigue. Thus, MRI and P
      31 MRS are useful in assessing the status of patients with inflammatory
      myopathies during treatment with prednisone and immunosuppressive drugs.

PMID- 11470054
TI  - Amyopathic dermatomyositis.
AB  - Amyopathic dermatomyositis is a variant of dermatomyositis that is characterized
      by the typical skin rash but without the muscle abnormalities. It has been
      proposed that the amyopathic and myopathic forms of dermatomyositis exist on a
      continuum, a concept that is supported by family and genetic studies and the
      observation that a small proportion of amyopathic patients transform to a frankly
      myopathic state. The amyopathic state is defined by a lack of muscle weakness and
      through diagnostic tests, including serum muscle enzymes, electromyogram studies,
      and muscle biopsies, that are usually normal or show only minimal abnormalities.
      Despite the lack of weakness, many patients complain of debilitating fatigue.
      More sensitive measures of muscle function, such as P-31 magnetic resonance
      spectroscopy, suggest that muscle metabolism is abnormal in amyopathic patients.
      The amyopathic form is more commonly seen in adults than in children, although
      juvenile cases are reported. Some early series suggested no association with
      underlying malignancies, but recent reports indicate that malignancies occur.
      Determining whether a patient has amyopathic rather than myopathic disease may
      have prognostic implications.

PMID- 11470055
TI  - [Olanzapine efficacy in the treatment of cocaine abuse in methadone maintenance
      patients. Interaction with plasma levels].
AB  - INTRODUCTION: The aim of this study was to evaluate the efficacy of the treatment
      with antipsychotic olanzapine in cocaine abuse methadone patients. The decrease
      or interruption of cocaine consume as well as the possible pharmacokinetic
      interaction between olanzapine and methadone were studied. MATERIAL AND METHODS:
      Patients (n= 21) include in a methadone maintenance program (14 months), with DSM
      IV criteria for opioid and cocaine dependence and without schizophrenic
      diagnostic, were treated with olanzapine 5 to 10 mg/day. The therapeutic outcomes
      were assessed by personal interviews, cocaine consumption, changes of consumption
      patrons (via of administration) and secondary effects to olanzapine. Withdrawal
      symptoms were measured by means of the abbreviate version of the scale of Gossop.
      Cocaine used was measured by urine analysis (enzymoimmnuoassay). The possible
      pharmacokinetic interaction between olanzapine and methadone was measured in
      plasma before and during the treatment in 15 patients. RESULTS: Olanzapine
      combined with methadone in cocaine abusers was well tolerated in an important
      proportion of patients. Moreover the consumption of cocaine was decreased or
      stopped in 53,2% of the patients. In addition, no withdrawal syndrome was
      observed in any patients. Furthermore the ratios of methadone plasma levels did
      not change in relation to the dose before and during the treatment, suggesting a
      lack of pharmacokinetic interaction between methadone and olanzapine.
      CONCLUSIONS: In conclusion the results of this preliminary study, led us to
      advance that olanzapine could be a useful treatment for cocaine abuse at least in
      patients in a Methadone Maintenance Program, with the advantage of not to induce
      any pharmacokinetic interaction with methadone.

PMID- 11470056
TI  - [Crime-related aspects in heroin addict patients: relationship between crime and
      delinquency].
AB  - BACKGROUND: Criminological studies have been specially influenced by those social
      factors relationated with drug dependence. Data from Criminology and Law insist
      on relationship between social factor and criminological events, but not defining
      the direction of this correlation. OBJECTS: We present data about criminological
      situation of an heroin addict patients sample evaluated by consultation-liasion
      psychiatry in Ramon y Cajal hospital in Madrid. We study legal, social and
      clinical variables and their relationship. METHOD: We use descriptive analysis
      and logistic regression to study social, legal and clinical variables of a 411
      patients sample, using clinical report protocol. CONCLUSIONS: Those patients
      affected by HIV-1 have higher criminality index, with lower social, economic and
      educational level than those not affected. These results suggest an
      interdependence between delinquency and marginality with an early beginning of
      both.

PMID- 11470057
TI  - [Influence of psychiatric disorders in the effectiveness of a long-term methadone
      maintenance treatment].
AB  - OBJECTIVES: To obtain knowledge of the psychiatric disorders of a heroin
      dependent population undergoing MMT and the influence of such on the outcomes of
      treatment for dependence. METHODS: 132 opiate dependents undergoing MMT in Drug
      Addiction Treatment Unit, Aviles (Spain) were followed-up over 6 years of
      treatment. At the beginning and after 6 years of treatment an Ad hoc protocol
      (sociodemographic and clinical variables) was administered. Analyses of HIV and
      urine (opiates, cocaine and benzodiacepines) were made throughout treatment. The
      Goldeberg Anxiety and Depression Scale (GADS) and the International Personality
      Disorder Examination (IPDE) were also administered. RESULTS: The effectiveness of
      MMT was high, with evident social and clinical improvement. The following
      disorders were diagnosed: affective 29.7%, anxiety 19.1%, psychotic 11.8% and
      personality 51.1%. Anxiety and affective disorders were related with heroin and
      benzodiacepine use and with being HIV+. Personality disorders were more prevalent
      in older addicts, those unemployed and patients with court cases pending, and in
      those with cocaine and benzodiacepine use. Dose of methadone was not related with
      psychiatric disorders. CONCLUSIONS: Psychiatric disorders (affective, anxiety and
      personality disorders) were frequent and linked to worse treatment outcomes (drug
      use, criminal activities). In some patients, there was a HIV-depression-drug use
      relationship, and these patients clearly need a specific psychosocial
      intervention. In order for MMT programmes to be more effective greater attention
      needs to be paid to mental health problems in these patients.

PMID- 11470058
TI  - [Subjective experience and quality of life in schizophrenia].
AB  - The term quality of life has been gradually introduced in the field of
      Psychiatry. This term tries to integrate not only the symptoms in Psychiatric
      patients, but also other aspects, like individual perceptions, personal
      expectations, degree of independence, etc., in order to achieve a global
      understanding of the patient. The are few studies on quality of life in
      schizophrenia, especially there is a lack of self assessment scales that the
      patients can fill out about themselves and their psychological environment. The
      Seville Quality of Life Questionnaire tries to evaluate the subjective experience
      of patients with schizophrenia about their illness. The Seville Quality of Life
      Questionnaire also checks the presence or absence of groups of patients with
      schizophrenia with a better or worst quality of life. We have assessed 222
      subjects that meet ICD-10 criteria diagnostic for schizophrenia, with the Seville
      Quality of Life Questionnaire, the Positive and Negative Symptom Scale specific
      psychopathology scale and the AMDP system general psychopathology scale. Our
      results show two clearly differentiate groups: one with better (Group 2: 108
      patients) and one with worse (Group 1: 81 patients) quality of life. However, 33
      patients could not be included in any of the two groups. In the worse quality of
      life group the most prominent factors were: lack of cognitive grasp, perplexity,
      fear of loss of control, and contained hostility. These four factors have a great
      influence on the worse quality of life. When we compare the Seville Quality of
      Life Questionnaire data with several the Positive and Negative Symptom Scale
      scores, we saw that the group of worse quality of life presents higher scores on
      both Negative and Positive Symptoms of schizophrenia, and also in the Positive
      and Negative Symptom Scale general psychopathology scale. In the AMDP system
      general psychopathology scale we saw three groups of significant symptoms in the
      Seville Quality of Life Questionnaire: 1. Difficult relationships with the
      external world, 2. Difficulty to understand what it happening (loss of
      associations); and 3. Affective alterations (ambivalence).Finally, these data
      suggests that it is probable that the Seville Quality of Life Questionnaire could
      be able to build a typology of patients with schizophrenia more centred in their
      pathology that in their psychophatology.

PMID- 11470059
TI  - [Long-term relapse prevention with risperidone in 215 schizophrenic patients].
AB  - INTRODUCTION: A total of 215 schyzophrenic patients according to DSM-IV criteria
      in treatment on risperidone were included in an open label postmarketing
      surveillance 18 months study to evaluate safety and effectivity of the drug in
      preventing relapses. METHODS: The Brief Psychiatric Rating Scale, Global
      Functional Assessment Scale and the Clinical Global Impression were used to
      assess. Safety was evaluated by the UKU subscale for neurological side effects.
      RESULTS: A 82.1% of the patients continued risperidone medication without relapse
      during the 18 month period. Risperidone was used at a mean dosage of 5.69 2.41
      mg/d. DISCUSSION: Patients improved psychotic symptoms and global activity, and
      significant reductions were observed in mean total UKU subscale for neurological
      side effect score. 91.7% of the patients did not report any adverse event; only 2
      (1.2%) patients dropt out because of intolerance.

PMID- 11470060
TI  - [A revised Iowa collateral head injury interview: a new instrument for the
      assessment of traumatic psychosocial frontal symptoms].
AB  - OBJECTIVE: To validate a semi-structured Revised Iowa Collateral Head Injury
      Interview (RICHII) to assess post-traumatic, psychosocial frontal symptoms.
      METHOD: 1. To revise the RICHII in the light of recent research findings and
      previous pilot studies. 2. External experts assure face and content validity. 3.
      Standard reliability and validity study in a sample of consecutive patients
      fulfilling inclusion and exclusion criteria of severe head trauma. 4. Principal
      component analysis and distribution of results of RICHII administration to the
      full sample (N= 55). RESULTS: Several original items were modified and two new
      items (inappropriate euphoria and affective unstableness) were incorporated, as
      well as a new, graded scoring system. Feasibility, internal consistency
      (Cronbach's alfa= 0.94), inter-rater reliability (n= 40, kappa= 0.60) and test
      retest reliability (n= 25, kappa= 0.70) were quite acceptable. Four factors
      emerged in the factor analysis, explaining a high percentage of the variance;
      they tend to reflect modern knowledge in the field and are judged to support the
      construct validity of the RICHII. More than two thirds of patients (70.9%) scored
      high in at least one of the items. CONCLUSION: This is the first report about the
      reliability and validity of a collateral interview to assess post-traumatic,
      psychosocial frontal symptoms.

PMID- 11470061
TI  - [Instruments of depression assessment in schizophrenia].
AB  - Lately, numerous reports have focused on the evaluation of depressive symptoms of
      schizophrenia. This assessment has been hampered by the temporal variability of
      the depressive symptoms and by their overlap with both the negative symptoms of
      schizophrenia and the extrapyramidal effects of the antipsychotic treatment. So
      far, classical assessment instruments such as the Hamilton Depression Rating
      Scale (HDRS) or the Montgomery-Asberg Rating Depression Scale (MARDS) have been
      used in those patients suffering from schizophrenia with depressive
      symptomatology, despite the important limitations concerning their use in
      subpopulations other than the one they have been developed for. New specific
      depression scales for schizophrenia such as the Calgary Depression Scale for
      Schizophrenics (CDSS) seems to have more efficiency and ability to distinguish
      between depression, negative and extrapyramidal symptoms. The present paper
      reviews the instruments used so far on the assessment of depressive
      symptomatology in schizophrenic patients.

PMID- 11470062
TI  - [Gender differences in mood disorders. A literature review].
AB  - The study of gender differences in mood disorders may have important clinical
      implications such as identifying clinical subtypes or symptoms clusters specific
      to each sex, and will help better understand pathophysiological mechanisms
      involved in affective illness. In unipolar depression the most frequent gender
      differences found are a greater prevalence of depression in women than in men and
      a worst outcome in women: they are more likely to have a chronic and recurrent
      course with longer episodes. Also, depressed women have higher rates of
      comorbidity than depressed men. Gender differences in response to treatment are
      as yet inconclusive. Women tend to display more side effects at the usual doses.
      It may be useful to consider a dosage adjustment during the premenstrual period
      and if hormonal therapies are being administered. No gender differences in the
      prevalence of bipolar disorder have been found, except for a greater incidence of
      rapid cycling in women (ratio 3:1).

PMID- 11470063
TI  - [Pseudoneurotic schizophrenia: a case report].
AB  - We report a 34-years old woman, with a history of social anxiety, specific
      phobias and generalized anxiety symptoms, who presented for treatment with panic
      attacks and depression. She was started on paroxetine and presented exacerbation
      of the affective syndrome and onset of psychotic symptoms that persisted after
      the suspension of the antidepressant and responded to sulpiride and later to
      thioridazine. We discuss the pertinence of the diagnosis of pseudoneurotic
      schizophrenia and the comorbidity between psychosis and anxiety symptoms.

PMID- 11470064
TI  - [Wernicke-Korsakoff syndrome: malignant tumour as triggering factor].
AB  - Gastrectomy, alcoholism and malignant tumour are three predisponing risk factors
      for the development of Wernicke-Korsakoff syndrome. We described the clinical
      case of a patient with history of alcoholism that developed Wernicke-Korsakoff
      syndrome 30 years after undergoing gastrectomy. This patient had, in the last
      year, a diagnostic for prostatic adenocarcinoma and changes in dietary habits. We
      presented the clinical and neuropathological features of the Wernicke-Korsakoff
      syndrome. As well as some aspects in the treatment and prognosis.

PMID- 11470067
TI  - [Tumoral secretion markers: something more than clinical indicators].

PMID- 11470068
TI  - [Present status of the nuclear medicine studies in infections and inflammatory
      processes in Spain].
AB  - The results of the survey carried out in our country during the present year on
      the nuclear medicine studies in infectious and inflammatory studies during 1999
      are presented. They survey was sent to 89 centers with a nuclear medicine
      service, 45 of which were publicly owned and 44 of which were privately owned. A
      total of 32 centers (36%) replied to the survey. 51.1% (23 out of 45) of the
      public hospitals responded but only a 20.5% (9 out of 44) of the private ones
      did.A total of 70.92% (4,344) out of the 6,125 explorations were carried out to
      discard and infectious process and 29.07% (1,781) to discard inflammation. The
      most frequent indication was to discard infections resulting from bone prostheses
      (2,099 explorations accounting for 48.31% of the total infectious process),
      followed by bone infection or osteomyelitis (965 explorations, 22.21% of the
      total). Within the osteomyelitis cases, acute processes motivated the most
      frequent requests (60.31% of all osteomyelitis cases). Assessment of the scope
      and localization of the intestinal inflammatory disease was the most frequent
      request in the inflammation group. Concerning the radiopharmaceuticals used,
      99mTc HMAPO or 111I marked-leukocytes were ranked first, these accounting for 47%
      of the cases. Gallium, used in 44% of all cases, was the second most frequently
      used, even though it continues to be the more commonly used radiopharmaceuticals
      for infectious processes.

PMID- 11470069
TI  - [Preoperative serum levels of the carcinoembryonic antigen (CEA) and prognosis in
      colorectal cancer].
AB  - OBJECTIVE: To analyze the prognostic value of the preoperative serum levels of
      the carcinoembryonic antigen (CEA) in primary colorectal carcinoma. MATERIAL AND
      METHODS: Preoperative serum levels of CEA were analyzed in 275 colorectal cancer
      patients, who were followed up for a minimum of 5 years, or until death. RESULTS:
      The percentage of positivities for the preoperative serum levels of CEA (> 6
      ng/ml) was positively and significantly associated with the tumoral stage (A:
      10,5%; B: 38,8%; C: 32,2%; y D: 72%; p < 0,0001). In addition, the elevated serum
      values of the antigen were significantly associated, in the univariate analysis,
      with short survival in the overall group of patients (p < 0,0001). However, the
      multivariate analysis only showed an independent prognosis value of the CEA in
      the subgroup of patients with stage C tumors. CONCLUSIONS: Preoperative serum
      levels of CEA may be useful to predict tumoral extension, and also for the
      prognosis regarding stage C colorectal cancer patients.

PMID- 11470070
TI  - [Study of the cytosolic concentrations of the tissue poly-peptide specific (TPS)
      antigen in infiltrating ductal carcinomas of the breast. Positive relationship
      with hormone dependency and negative with cellular proliferation].
AB  - INTRODUCTION: The tissue-specific polypeptide antigen (TPS) is an epitope of the
      tissue polypeptide antigen (TPA) which is defined by the M3 monoclonal antibody
      and is related to cytokeratin 18. Several groups have demonstrated its value as a
      useful parameter in the follow-up of some tumors. This work has aimed to study
      the TPS cytosolic levels in infiltrating ductal carcinomas of the breast (IDC)
      and their possible correlations with other clinical-biological parameters.
      PATIENTS AND METHODS: The TPS was determined by means of an immunoradiometric
      assay (Beki Diagnostics. Sweden). Other parameters included in the study were the
      estrogen receptors (ER), progesterone receptors (PR), pS2, cathepsin D, tissue
      type plasminogen activator (t-PA), tumor size, axillary lymph node involvement,
      distant metastases, histological grade, ploidy and S-phase. RESULTS: The TPS
      cytosolic levels ranged from 1.8 to 606.3 KU/mg prt. (median 110.2) and had a
      significant correlation with the ER (r: 0.721), PR (r: 0.287), cathepsin D (r:
      0.550) and t-PA (r:0.436). The TPS positive (> 110.2 KU/mg prt.) carcinomas had
      higher levels of ER (p: 0.001), PR (p: 0.021), pS2 (p: 0.058), cathepsin D (p:
      0.000) and t-PA (p: 0.053) than the TPS negative tumors. When the IDC were
      classified according to S-phase values, we observed that the positive cases (S
      phase > 8.1%, which represents the median value of all carcinomas) had lower
      levels of TPS (p: 0.046) than the negative tumors. Likewise, the GoG1 cellular
      fraction correlated positively and significantly with the TPS cytosolic levels
      (p: 0.000). CONCLUSIONS: Based on our results, we suggest that there is a
      positive correlation between the TPS cytosolic levels and hormone-dependence
      parameters, as well as an inverse correlation between these and the cellular
      proliferation parameters. Based on the above, we consider that it is worthwhile
      to carry out further studies on cytosolic TPS in order to investigate its
      possible value as a prognostic parameter in breast carcinomas.

PMID- 11470071
TI  - [Value of 123I-MIBG scanning, neuron-specific enolase and serum ferritin in the
      diagnosis and follow-up of patients with neuroblastoma].
AB  - INTRODUCTION: The neuroblastoma (NB) is one of the most common pediatric
      malignant neoplasms. The most commonly used tumor markers in the diagnosis and
      follow-up of this tumor are the serum neuron-specific enolase (NSE), ferritin and
      lactic dehydrogenase and urinary vanillymandelic and homovanillic acid. The
      common imaging modalities are CT, MRI and 123I or 131I-meta-iodobenzylguanidine
      scintigraphy. AIM: The aim of this study is to assess the value of 123I-meta
      iodobenzylguanidine (MIBG) scintigraphy and serum determinations of NSE and
      ferritin in the diagnosis and evolution of NB patients. MATERIAL AND METHODS: 20
      patients (8 female, 12 male) whose ages ranged from 2 months to 9 years with a
      mean age of 2.64 years diagnosed of NB. 47 123I-MIBG scans, 47 NSE determinations
      and 47 ferritin ones were selected. RESULTS: At the time of diagnosis, 100% of
      the 123I-MIBG scans were positive. 65% of NSE determinations presented clearly
      pathological levels and 15% were very near to the cut-off point. Only 45% of the
      ferritin levels were increased. The differences between the lesions visible by
      123I-MIBG scanning before and 3 months after treatment as well as NSE and
      ferritin levels were studied. When the Student's T test was applied, we found
      statistically significant pre and post-treatment differences in 123I-MIBG
      scanning and NSE. In the case of ferritin, there was no statistical significance
      in spite of the decrease in the values. The direct correlation and Spearman
      correlation between laboratory data and 123I-MIBG scanning as well as correlation
      between NSE and ferritin were also studied. There was a good correlation between
      123I-MIBG and NSE and between NSE and ferritin. We have also studied the data in
      7 relapses. CONCLUSIONS: 123I-MIBG scintigraphy and serum determination of NSE
      are two successful diagnostic tools for the diagnosis and evolution of NB
      patients.

PMID- 11470072
TI  - [Clinical significance of the increased uptake of a solitary rib lesion in the
      bone scintigraphy. Based on an osteoblastoma].
AB  - A case of a bone tumor located in the right sixth rib detected by means of the
      bone scan as a solitary lesion is presented. Although the chest X-ray and CT were
      normal, a low signal intensity on T1 images and high-intensity on T2 images were
      seen in the MRI. The post-surgical histological diagnosis was osteoblastoma. A
      review of the clinical significance of solitary rib lesions which appear with
      increased uptake on bone scan was performed. When a differential diagnosis is
      made of a solitary rib lesion that appears on a bone scan, osteoblastoma should
      be considered.

PMID- 11470073
TI  - [Scintigraphy with 111In-octreotide in a case of primary hepatic gastrinoma].
AB  - Gastrinomas are uncommon tumors which are difficult to locate. They are often
      located in the head of the pancreas. About two-thirds of them are malignant,
      their growth is slow and they usually metastasize in the liver. In about 25% of
      cases, the Zollinger-Ellison (Z-E) syndrome is included in the multiple endocrine
      neoplasm type 1 syndrome (MEN 1).A 14-year old male patient presenting an episode
      of abdominal perforation which required emergency surgery is reported. The
      abdominal ultrasonography, CT scan and magnetic resonance revealed a single
      lesion in the left liver lobe, suggesting metastasis. Significantly increased
      levels of serum gastrin suggested a diagnosis of Z-E syndrome. A study with 111In
      octreotide was required to locate the primary tumor and evaluate its extent. The
      scintigraphy showed only one abnormal uptake focus in the left liver lobe. Post
      surgery scintigraphy studies revealed the presence of metastatic adenopathies
      which were removed after a second surgery. No pathologic findings were observed
      in the last nuclear medicine study. The somatostatin receptor scintigraphy is the
      most sensitive method to locate primary gastrinomas and to assess the tumoral
      dissemination in patients with Z-E Syndrome.

PMID- 11470074
TI  - [Functional neuroimaging in patients with rapid cycling bipolar depression].
AB  - Bipolar patients with a rapid cycling clinical course constitute an interesting
      sub-group for studies focused on the pathophysiology of the disorder, since
      several switches can be studied by the investigators in a short period of time.
      At present, functional neuroimaging techniques, as SPECT and PET, may be used for
      the neurobiological study of affective disorders. Few longitudinal functional
      neuroimaging studies assessing the different phases of bipolar disorder have been
      carried out. However, the published data suggest an asymmetrical temporal lobe
      dysfunction in depressive and manic phases of bipolar depression. Further studies
      with larger samples of patients are needed in order to improve our knowledge of
      the pathophysiology of bipolar disorder.

PMID- 11470075
TI  - [Diagnosis of occult bone lesions exercise-related during bone scintigraphy].

PMID- 11470076
TI  - [Rib fractures after cardiopulmonary resuscitation].

PMID- 11470077
TI  - [Evidence based medicine. Application to nuclear medicine. Diagnostic slope. Part
      II].

PMID- 11470082
TI  - Morphology of fast-tumbling bicelles: a small angle neutron scattering and NMR
      study.
AB  - Bilayered micelles, or bicelles, which consist of a mixture of long- and short
      chain phospholipids, are a popular model membrane system. Depending on
      composition, concentration, and temperature, bicelle mixtures may adopt an
      isotropic phase or form an aligned phase in magnetic fields. Well-resolved (1)H
      NMR spectra are observed in the isotropic or so-called fast-tumbling bicelle
      phase, over the range of temperatures investigated (10-40 degrees C), for molar
      ratios of long-chain lipid to short-chain lipid between 0.20 and 1.0. Small angle
      neutron scattering data of this phase are consistent with the model in which
      bicelles were proposed to be disk-shaped. The experimentally determined
      dimensions are roughly consistent with the predictions of R.R. Vold and R.S.
      Prosser (J. Magn. Reson. B 113 (1996)). Differential paramagnetic shifts of head
      group resonances of dimyristoylphosphatidylcholine (DMPC) and
      dihexanoylphosphatidylcholine (DHPC), induced by the addition of Eu(3+), are also
      consistent with the bicelle model in which DHPC is believed to be primarily
      sequestered to bicelle rims. Selective irradiation of the DHPC aliphatic methyl
      resonances results in no detectable magnetization transfer to the corresponding
      DMPC methyl resonances (and vice versa) in bicelles, which also suggests that
      DHPC and DMPC are largely sequestered in the bicelle. Finally, (1)H spectra of
      the antibacterial peptide indolicidin (ILPWKWPWWPWRR-NH(2)) are compared, in a
      DPC micellar phase and the above fast-tumbling bicellar phases for a variety of
      compositions. The spectra exhibit adequate resolution and improved dispersion of
      amide and aromatic resonances in certain bicelle mixtures.

PMID- 11470083
TI  - Slippage and uncoupling in P-type cation pumps; implications for energy
      transduction mechanisms and regulation of metabolism.
AB  - P-type ATPases couple scalar and vectorial events under optimized states. A
      number of procedures and conditions lead to uncoupling or slippage. A key
      branching point in the catalytic cycle is at the cation-bound form of E(1)-P,
      where isomerization to E(2)-P leads to coupled transport, and hydrolysis leads to
      uncoupled release of cations to the cis membrane surface. The phenomenon of
      slippage supports a channel model for active transport. Ability to occlude
      cations within the channel is essential for coupling. Uncoupling and slippage
      appear to be inherent properties of P-type cation pumps, and are significant
      contributors to standard metabolic rate. Heat production is favored in the
      uncoupled state. A number of disease conditions, include ageing, ischemia and
      cardiac failure, result in uncoupling of either the Ca(2+)-ATPase or Na(+)/K(+)
      ATPase.

PMID- 11470084
TI  - Spin-label electron paramagnetic resonance studies on the interaction of avidin
      with dimyristoyl-phosphatidylglycerol membranes.
AB  - The interaction of avidin--a basic protein from hen egg-white--with dimyristoyl
      phosphatidylglycerol membranes was investigated by spin-label electron
      paramagnetic resonance spectroscopy. Phosphatidylcholines, bearing the nitroxide
      spin label at different positions along the sn-2 acyl chain of the lipid were
      used to investigate the effect of protein binding on the lipid chain-melting
      phase transition and acyl chain dynamics. Binding of the protein at saturating
      levels results in abolition of the chain-melting phase transition of the lipid
      and accompanying perturbation of the lipid acyl chain mobility. In the fluid
      phase region, the outer hyperfine splitting increases for all phosphatidylcholine
      spin-label positional isomers, indicating that the chain mobility is decreased by
      binding avidin. However, there was no evidence for direct interaction of the
      protein with the lipid acyl chains, clearly indicating that the protein does not
      penetrate the hydrophobic interior of the membrane. Selectivity experiments with
      different spin-labelled lipid probes indicate that avidin exhibits a preference
      for negatively charged lipid species, although all spin-labelled lipid species
      indirectly sense the protein binding. The interaction with negatively charged
      lipids is relevant to the use of avidin in applications such as the
      ultrastructural localization of biotinylated lipids in histochemical studies.

PMID- 11470085
TI  - Synthesis of the chelator lipid nitrilotriacetic acid ditetradecylamine (NTA
      DTDA) and its use with the IAsys biosensor to study receptor-ligand interactions
      on model membranes.
AB  - This work describes the synthesis and use of the chelator lipid, nitrilotriacetic
      acid ditetradecylamine (NTA-DTDA). This lipid is readily dispersed in aqueous
      media, both alone and when mixed with carrier lipids like
      dimyristoylphosphatidylcholine (DMPC). Fluorescence microscopic examination of
      membranes deposited from NTA-DTDA-containing liposomes shows that NTA-DTDA mixes
      uniformly with the carrier lipid, and does not phase separate. NTA-DTDA-membranes
      deposited onto the sensing surface of IAsys biosensor cuvettes show good
      stability, permitting use of the biosensor to study protein interactions.
      Hexahistidine-tagged proteins including recombinant forms of the extracellular
      regions of murine B7.1 (B7.1-6H) and of the human erythropoietin receptor (EPOR
      6H) bind to NTA-DTDA-membranes; the stability of binding is dependent on both
      protein concentration, and density of NTA-DTDA. Kinetic measurements show that
      high stability of anchored proteins (t(1/2) approximately 10-20 h, apparent K(d)
      approximately 1 nM) can be achieved using membranes containing 25 mol% NTA-DTDA,
      but low levels of bound protein (<200 arc seconds). The system is used to study
      the interaction of human EPO with the EPOR anchored onto NTA-DTDA-membranes. In
      addition to the biological applications reported recently, the results show that
      NTA-DTDA can be a useful reagent in the study of receptor-ligand interactions.

PMID- 11470086
TI  - Expression of sodium pump isoforms and other sodium or calcium ion transporters
      in the heart of hypertensive patients.
AB  - The sodium pump (Na(+),K(+)-ATPase; EC 3.6.1.37) of animal cell membranes is the
      enzyme responsible for the maintenance of membrane potential, for the function of
      secondary active transporters, and for osmoregulation of the cell. Since
      inhibition of the enzyme by cardiac glycosides results in increased contractility
      of the heart muscle and increased blood pressure, we were interested in whether
      there is a correlation between hypertension and expression of the various
      isoforms of the sodium pump. In addition, we also examined the expression of the
      isoforms of the sarcoplasmic and plasma membrane Ca(2+)-ATPase, the Na(+)/Ca(2+)-
      and Na(+)/H(+)-exchangers, and Na(+) channel and Ca(2+) channel isoforms. Total
      mRNA was isolated from 50 mg tissue from the right atrium of hypertensive and
      normotensive patients who were undergoing cardiac surgery. After reverse
      transcription and subsequent amplification of ion transporter-specific cDNA
      fragments by polymerase chain reaction (PCR) in the presence of [alpha
      (32)P]dCTP, quantification of the amplified fragments was carried out by the
      Phosphorimager technique. The data obtained show that the alphal subunit mRNA is
      expressed similarly in normotensive and hypertensive patients. The amount of
      alpha2 subunit mRNA, however, is increased 5-fold in hypertensive patients. In
      the same group, the amount of alpha3 isoform is also significantly increased,
      although not as dramatically as the alpha2 isoform. Besides the Na(+),K(+)-ATPase
      isoforms, a significant increase in the expression of mRNA for the Na(+)/Ca(2+)
      exchanger and the plasma membrane Ca(2+)-ATPase isoforms was detected. It is
      possible that the observed changes in mRNA expression for these ion transporters
      reflect compensatory mechanisms to overcome a defective Na(+) and Ca(2+)
      metabolism in the tissues of hypertensive patients or reflect defects directly
      involved in the cause of hypertension. The expression of mRNA for all other
      transporters investigated was unaltered.

PMID- 11470087
TI  - A pyrrolidine-based specific inhibitor of cytosolic phospholipase A(2)alpha
      blocks arachidonic acid release in a variety of mammalian cells.
AB  - We analyzed a recently reported (K. Seno, T. Okuno, K. Nishi, Y. Murakami, F.
      Watanabe, T. Matsuur, M. Wada, Y. Fujii, M. Yamada, T. Ogawa, T. Okada, H.
      Hashizume, M. Kii, S.-H. Hara, S. Hagishita, S. Nakamoto, J. Med. Chem. 43
      (2000)) pyrrolidine-based inhibitor, pyrrolidine-1, against the human group IV
      cytosolic phospholipase A(2) alpha-isoform (cPLA(2)alpha). Pyrrolidine-1 inhibits
      cPLA(2)alpha by 50% when present at approx. 0.002 mole fraction in the interface
      in a number of in vitro assays. It is much less potent on the cPLA(2)gamma
      isoform, calcium-independent group VI PLA(2) and groups IIA, X, and V secreted
      PLA(2)s. Pyrrolidine-1 blocked all of the arachidonic acid released in Ca(2+)
      ionophore-stimulated CHO cells stably transfected with cPLA(2)alpha, in zymosan-
      and okadaic acid-stimulated mouse peritoneal macrophages, and in ATP- and Ca(2+)
      ionophore-stimulated MDCK cells.

PMID- 11470088
TI  - Self-assembly of influenza hemagglutinin: studies of ectodomain aggregation by in
      situ atomic force microscopy.
AB  - We have used in situ tapping mode atomic force microscopy (AFM) to study the
      structural morphology of two fragments of the influenza hemagglutinin protein
      bound to supported bilayers. The two proteins that we studied are the bromelain
      cleaved hemagglutinin (BHA), corresponding to the full ectodomain of the
      hemagglutinin protein, and FHA2, the 127 amino acid N-terminal fragment of the
      HA2 subunit of the hemagglutinin protein. While BHA is water soluble at neutral
      pH and is known to bind to membranes via specific interactions with a viral
      receptor, FHA2 can only be solubilized in water with an appropriate detergent.
      Furthermore, FHA2 is known to readily bind to membranes at neutral pH in the
      absence of a receptor. Our in situ AFM studies demonstrated that, when bound to
      supported bilayers at neutral pH, both these proteins are self-assembled as
      single trimeric molecules. In situ acidification resulted in further lateral
      association of the FHA2 without a large perturbation of the bilayer. In contrast,
      BHA remained largely unaffected by acidification, except in areas of exposed mica
      where it is aggregated. Remarkably, these results are consistent with previous
      observations that FHA2 promotes membrane fusion while BHA only induces liposome
      leakage at low pH. The results presented here are the first example of in situ
      imaging of the ectodomain of a viral envelope protein allowing characterization
      of the real-time self-assembly of a membrane fusion protein.

PMID- 11470089
TI  - Depolarization of the liver cell membrane by metformin.
AB  - Metformin (1,1-dimethylbiguanide; MET) is used in the treatment of type 2
      diabetes mellitus. MET's antihyperglycemic action depends at least in part on its
      inhibitory effect on hepatic gluconeogenesis. As to gluconeogenesis from amino
      acids (e.g. L-alanine), this is associated with an inhibition of L-alanine uptake
      into hepatocytes. Since this uptake is mediated by an electrogenic transport
      mechanism, the aim of the present study was to investigate whether MET has an
      influence on the liver cell membrane potential which might explain its inhibitory
      effect on L-alanine uptake. The experiments were performed in vivo in
      anesthetized rats and in vitro using superfused mouse liver slices with the
      conventional microelectrode technique. In vivo, MET (160 mg/kg intraperitoneally
      (i.p.)) significantly depolarized (dV) the liver cell membrane by 6 mV. MET (1
      mmol/l) also depolarized the liver cell membrane in vitro (e.g. 15 min after
      start of superfusion: dV=8 mV). MET's effect was at least partly reversible.
      Glucagon (10(-7) mol/l), which hyperpolarized the liver cell membrane, abolished
      MET's effect. Further, the MET-induced depolarization was completely absent
      during superfusion with low Cl(-) ([Cl(-)]=27 mmol/l) medium, and significantly
      attenuated by the Cl(-) channel blocker NPPB (25 micromol/l). While MET's effect
      was only somewhat attenuated by blockade of the Na(+)/K(+)/2Cl(-) cotransporter
      or by superfusion with (HCO(-)(3)-free) HEPES buffer, the carboanhydrase blocker
      acetazolamide (1 mmol/l) or blockade of the HCO(-)(3)/Cl(-) exchanger by DIDS
      (100 micromol/l), which, however, also blocks Cl(-) channels, abolished its
      effect. The depolarization of the liver cell membrane by MET was unaffected by a
      blockade of K(+) channels with Ba(2+), a blockade of the Na(+)/K(+) pump or
      superfusion with low Na(+) medium ([Na(+)]=26 mmol/l). According to these
      results, the MET-induced depolarization of the liver cell membrane could be due
      to an activation of the Cl(-)/HCO(-)(3) exchanger and thus depend on
      intracellular HCO(-)(3) formation. This activation could then lead to a
      disturbance of the equilibrium between intra- and extracellular Cl(-) and
      therefore to an enhanced Cl(-) efflux via Cl(-) channels. It is plausible that
      the depolarizing effect induced by MET is associated with its inhibitory effect
      on gluconeogenesis by inhibiting uptake of L-alanine and other amino acids into
      hepatocytes.

PMID- 11470090
TI  - Comparison of gramicidin A and gramicidin M channel conductance dispersities.
AB  - To explore the possible role of Trp side chains in gramicidin channel conductance
      dispersity, we studied the dispersity of gramicidin M (gM), a gramicidin variant
      in which all four tryptophan residues are replaced with phenylalanine residues,
      and its enantiomer, gramicidin M(-) (gM(-)), and compared them to that of
      gramicidin A (gA). The conductances of highly purified gM and gM(-) were studied
      in alkali metal solutions at a variety of concentrations and voltages, in seven
      different types of lipid, and in the presence of detergent. Like gA channels, the
      most common gM channel conductance forms a narrow band. However, unlike gA
      channels, where the remaining 5-30% of channel conductances are broadly
      distributed below (and slightly above) the main band, in gM there is a narrow
      secondary band with <50% of the main peak conductance. This secondary peak was
      prominent in NaCl and KCl, but significantly diminished in CsCl and RbCl. Under
      some conditions, minor components can be observed with conductances yet lower
      than the secondary peak. Interconversions between the primary conductance state
      and these yet lower conductance states were observed. The current-voltage
      relations for both primary and secondary gM channel types have about the same
      curvature. The mean lifetime of the secondary channel type is below one third
      that of the primary type. The variants represent state deviations in the peptide
      or adjacent lipid structure.

PMID- 11470091
TI  - Intermembrane transfer of polyethylene glycol-modified phosphatidylethanolamine
      as a means to reveal surface-associated binding ligands on liposomes.
AB  - In order to explore the use of exchangeable poly(ethylene glycol) (PEG)-modified
      diacylphosphatidylethanolamines (PE) to temporarily shield binding ligands
      attached to the surface of liposomes, a model reaction based on inhibition and
      subsequent recovery of biotinylated liposome binding to streptavidin immobilized
      on superparamagnetic iron oxide particles (SA magnetic particles) was developed.
      PEG-lipid incorporation into biotinylated liposomes decreased liposome binding to
      SA magnetic particles in a non-linear fashion, where as little as 0.1 mol% PEG-PE
      resulted in a 20% decrease in binding. Using an assay based on inhibition of
      binding, PEG(2000)-PE transfer from donor liposomes to biotinylated acceptor
      liposomes could be measured. The influence of temperature and acyl chain
      composition on the transfer of PEG-diacyl PEs from donor liposomes to acceptor
      liposomes, consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine, cholesterol
      and N-((6-biotinoyl)amino)hexanoyl)-1,2-distearoyl-sn-glycero-3
      phosphoethanolamine (54.9:45:0.1 mole ratio), was measured. Donor liposomes were
      prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (50 mol%), cholesterol
      (45 mol%) and 5 mol% of either PEG-derivatized 1,2-dimyristoyl-sn-glycero-3
      phosphoethanolamine (DMPE-PEG(2000)), 1,2-dipalmitoyl-sn-glycero-3
      phosphoethanolamine (DPPE-PEG(2000)), or 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine (DSPE-PEG(2000)). Transfer of DSPE-PEG(2000) to the donor
      liposomes was not detected under the conditions employed. In contrast, DMPE
      PEG(2000) was transferred efficiently even at 4 degrees C. Using an acceptor to
      donor liposome ratio of 1:4, the time required for DMPE-PEG(2000) to become
      evenly distributed between the two liposome populations (T(EQ)) at 4 degrees C
      and 37 degrees C was approx. 2 and <0.5 h, respectively. An increase in acyl
      chain length from C14:0 to C16:0 of the PEG-lipid resulted in a significant
      reduction in the rate of transfer as measured by this assay. The transfer of PEG
      lipid out of biotinylated liposomes was also studied in mice following
      intravenous administration. The relative rates of transfer for the various PEG
      lipids were found to be comparable under in vivo and in vitro conditions. These
      results suggest that it is possible to design targeted liposomes with the
      targeting ligand protected while in the circulation through the use of PEG-lipids
      that are selected on the basis of exchange characteristics which result in
      exposure of the shielded ligand following localization within a target tissue.

PMID- 11470092
TI  - In vitro and in vivo comparison of immunoliposomes made by conventional coupling
      techniques with those made by a new post-insertion approach.
AB  - Ligand-targeted liposomes have the potential to increase the therapeutic efficacy
      of antineoplastic agents. Recently, a combinatorial approach to the preparation
      of ligand-targeted liposomes has been developed, termed the post-insertion
      technique, which will facilitate the production of targeted liposomes. In this
      paper, Stealth immunoliposomes (SIL) coupled to anti-CD19 made by either a
      conventional coupling technique (SIL[anti-CD19]), or by the post-insertion
      technique (PIL[anti-CD19], were compared with respect to their in vitro binding
      and cytotoxicity and their ability to improve in vivo survival in tumor-bearing
      mice. The in vitro binding and uptake of PIL[anti-CD19] by CD19-expressing, B
      cell lymphoma (Namalwa) cells was similar to that of SIL[anti-CD19] and both were
      significantly higher than binding of non-targeted liposomes (SL). In addition, no
      significant differences were found between the respective in vitro cytotoxicities
      of doxorubicin-loaded PIL[anti-CD19] or SIL[anti-CD19], or in their in vivo
      therapeutic efficacy in a murine model of human B-lymphoma. Overall, the results
      demonstrate that the post-insertion technique is a simple, flexible and effective
      means for preparing targeted liposomal drugs for clinical applications.

PMID- 11470093
TI  - Evidence for membrane affinity of the C-terminal domain of bovine milk PP3
      component.
AB  - Component PP3 is a phosphoglycoprotein isolated from bovine milk with unknown
      biological function, which displays in its C-terminal region a basic amphipathic
      alpha-helix, a feature often involved in membrane association. According to that,
      the behaviour of PP3 and of a synthetic peptide from the C-terminal domain
      (residues 113-135) was investigated in lipid environment. Conductance
      measurements indicated that the peptide was able to associate and form channels
      in planar lipid bilayers composed of neutral or charged phospholipids.
      Electrostatic interactions seemed to promote voltage-dependent channel formation
      but this was not absolutely required since the pore-forming ability of the 113
      135 C-terminal peptide was also detected with the zwitterionic lipid bilayer.
      Additionally, a spectroscopic study using circular dichroism argues that the
      peptide adopts an alpha-helical conformation in interaction with neutral or
      charged micelles. Thus, the conducting aggregates in bilayers might be composed
      of a bundle of peptides in helical conformation. Besides, similar conductance
      measurements performed with the whole PP3 protein did not induce any channel
      fluctuations. However, with the latter, an early breakdown of the bilayers
      occurred, a finding that can be tentatively explained by a massive incorporation
      of PP3. In the light of the present results, it could be inferred that PP3
      membrane attachment may be achieved by oligomerization of the C-terminal
      amphipathic helical region.

PMID- 11470094
TI  - Critical parameters for functional reconstitution of glucose transport in
      Trypanosoma brucei membrane vesicles.
AB  - The glucose transporter of Trypanosoma brucei was reconstituted by incorporating
      Escherichia coli phospholipid liposomes into detergent-solubilised trypanosome
      membranes. Proteoliposome vesicles were formed by detergent dilution and used in
      glucose-uptake assays. The minima for functional reconstitution of the glucose
      transporter were established and used to probe the mechanism of glucose
      transport. The uptake pattern of radiolabelled glucose showed a counterflow
      transient at about 3 s, after which the sugar equilibrated across the
      proteoliposomal membrane. This observation is consistent with a facilitated
      transporter. There was a six-fold increase in the initial rate of glucose uptake
      compared to non-reconstituted or native membranes. In addition, the transporter
      exhibited stereospecificity to D-glucose but poorly transported L-glucose.
      Directionality, stereoselectivity or substrate specificity and cis-inhibition by
      phloridzin were therefore the main criteria for validation of glucose transport.
      The observed counterflow transient also provided further evidence for a
      facilitated glucose transporter within the trypanosome plasma membrane, and was
      the single most important criterion for this assertion. A stoichiometry of 0.78
      mol of glucose per mol of transporter was estimated.

PMID- 11470095
TI  - Managing health habits for myocardial infarction (MI) patients.
AB  - The study examined effects of the heart camp as a motivation enhancement program
      on cardiac risk reduction and behavioral modification in myocardial infarction
      (MI) patients. A total of 86 outpatients participated at the first heart camp and
      45 returned to the second one in 8 weeks. The first and second heart camps were
      daylong programs consisted of health assessment, education classes, and Q&A
      session with interdisciplinary team approach. At the completion of the heart
      camp, the participants showed significantly lower scores in cardiac risk factors,
      and significant improvements in motivational variables, especially, perceived
      benefits and perceived barriers as well as in the performance of diet and
      exercise behaviors. The study results confirm that it is possible to enhance
      motivation for chronic patients like MI patients by even short period of
      comprehensive educational program.

PMID- 11470096
TI  - Attitudinal patterns determining decision-making in severely ill elderly
      patients: a cross-cultural comparison between nurses from Sweden and Germany.
AB  - To explain determinants in the decision-making of nurses in the treatment of
      severely ill incompetent patients and to describe underlying attitudes,
      consecutive samples of nurses from Germany and Sweden have been investigated by
      means of a case scenario and a questionnaire. Whereas the level of dementia
      emerged as the only factor being significantly related with the treatment option
      within the Swedish group, patient's age, patient's wishes and ethical concerns
      were correlated among German nurses. The more the nurses have been able to
      participate in the provision of the available do-not-resuscitate order or of an
      advance directive, the less frequent they would perform CPR against the patient's
      wishes.

PMID- 11470097
TI  - Delya's story: from expert to novice, a critique of Benner's concept of context
      in the development of expert nursing practice.
AB  - The concepts identified within Benner's Nineteen Eighty Four research 'From
      Novice to Expert' have been widely adopted within UK nursing education and
      development. This paper combines a narrative from a post-registration student
      with analysis of the literature as a case study for gaining greater understanding
      of Benner's work in practice. Delya's story both validates aspects of the concept
      of skill acquisition and challenges some of the interpretations of the model
      within professional education. The focus of the critique of Benner's work within
      the literature to date has been on a deconstruction of the concepts and semantics
      of her work. In presenting verbatim extracts from a case study this paper seeks
      to move the focus to nursing practice.

PMID- 11470098
TI  - Nursing inputs to special schools in N. Ireland.
AB  - Children attending special schools often have healthcare needs that require
      ongoing medical and nursing care. Two postal surveys were undertaken of 47
      special schools in N. Ireland to determine the type of contact they had with
      nurses and the functions they fulfilled. Responses were received from 42 school
      principals and from the 11 Health and Social Service Trusts responsible for
      nursing services. It was found that nurses were based in nine of 42 schools while
      the remaining schools depended on a range of different visiting nurses. The
      nurses were involved in 'hands-on' tasks as well as giving advice and training to
      school personnel. Further research needs to define more closely the nursing needs
      of these pupils as well as evaluating the differential benefits of various
      nursing services to schools and how their inputs can be coordinated with those of
      other health professionals.

PMID- 11470099
TI  - Skilled nursing practice -- a qualitative study of the elements of nursing.
AB  - An understanding of skilled nursing practice has implications for the identity of
      nursing in service delivery, and for the learning environment of the developing
      nurse. Here I report a qualitative study, largely reliant on ethnography, which
      became a journey of exploration through accounts and descriptions given by nurses
      in a number of different practice settings. This journey is founded in an
      understanding of what I have called a phenomenological and psychosocial
      tradition, recognising the importance of a postmodern influence, which is in
      tension with a scientific and behavioural tradition. The emergence of four
      domains of skilled nursing practice in a contextualised narrative would seem to
      offer justification of assumptions concerning the value of embedded knowledge and
      intuitive clinical judgement in nursing practice, and lay a foundation for a
      qualitative study of the developing nurse.

PMID- 11470100
TI  - A comparative study of the experiences of violence of English and Swedish mental
      health nurses.
AB  - Recent studies suggest that violence in health care environments, especially
      mental health care, appears to be increasing. Although there is a lack of cross
      cultural studies to prove it, this increase in violence would seem to be an
      international phenomenon. The present study sought to compare the extent and
      nature of violence encountered by mental health nurses in Sweden and England.
      Systematic studies of violence have previously been carried out independently in
      both countries but this was the first attempt to compare levels of violence.
      Clearly defined study protocols were put in place, an operational definition of
      'violence' adhered to, and random samples recruited. A specially designed
      questionnaire was sent to every subject (Swedish nurses n=720; English nurses
      n=296) enquiring about the extent of nurses' exposure to violence, the nature and
      severity of the violence experienced, and the effect of violence on self-esteem
      and job satisfaction. Significant differences were found with English nurses
      experiencing more violence than their Swedish counterparts. Yet support for
      English nurses appeared to be less good than for Swedish nurses. Reasons for the
      differences are discussed along with possible measures to minimise the frequency
      of violence against nurses and the negative effects on their work.

PMID- 11470101
TI  - Specialist practice for UK community mental health nurses: the 1998--99 survey of
      course leaders.
AB  - Surveys of the leaders of the UK's post-qualifying education courses for
      community mental health nurses have taken place, on an annual basis, for over 10
      years. In this paper, findings from the survey undertaken in the 1998--99
      academic year are reported. These findings include: that most course leaders do
      not personally engage in clinical practice; that interprofessional education
      takes place at a minority of course centres, and that course philosophies and
      aims are characterised by an emphasis on both outcomes (in terms of, for example,
      skills acquisition, knowledge development and the ability to engage in reflective
      practice), and process (adult learning).

PMID- 11470102
TI  - Teenage pregnancy: on the road to social death.
AB  - This paper describes research into perceptions of teenage pregnancy at two
      different demographical locations in the UK. Ninety-five semi-structured
      interviews were conducted on a teenage pregnant population and a non-pregnant
      teenage population. Thematic analysis revealed three levels of influence causing
      social pressures on the teenage pregnancy and were structured as primary,
      secondary and subordinate depending on the emphasis within the discourse
      analysis. From this binary oppositions were identified which formed the
      theoretical constructs relating to the transition from one state to another which
      can be termed 'becoming'. When these states are negatively perceived they cause a
      form of impending doom and create social exclusion for the recipient. Finally, it
      was revealed that they succumb to the weight of social sanction and feel the
      prophecy of a 'social death'

PMID- 11470103
TI  - Combining qualitative and quantitative methods in assessing hospital learning
      environments.
AB  - Clinical education is a vital component in the curricula of pre-registration
      nursing courses and provides student nurses with the opportunity to combine
      cognitive, psychomotor, and affective skills. Clinical practice enables the
      student to develop competencies in the application of knowledge, skills, and
      attitudes to clinical field situations. It is, therefore, vital that the valuable
      clinical time be utilised effectively and productively. Nursing students'
      perception of the hospital learning environment were assessed by combining
      quantitative and qualitative approaches. The Clinical Learning Environment
      Inventory, based on the theoretical framework of learning environment studies,
      was developed and validated. The quantitative and qualitative findings reinforced
      each other. It was found that there were significant differences in students'
      perceptions of the actual clinical learning environment and their preferred
      learning environment. Generally, students preferred a more positive and
      favourable clinical environment than they perceived as being actually present.

PMID- 11470104
TI  - Nurses' informal teaching practices: their nature and impact on the production of
      patient care.
AB  - Nurses' informal teaching practices have been viewed as secondary to formal
      teaching. This article places them at the centre of professional nursing
      practice. On the basis of extended observation of 12 experienced surgical nurses,
      I assert they teach inexperienced physicians as well as patients, that their
      teaching is planned but more often informal and embedded in other work, and that
      their intent is to produce both understanding of health and illness practices and
      compliance with institutional policies and procedures. Nurses' informal teaching
      practices are essential to the ongoing production of patient care.

PMID- 11470105
TI  - Standing outside the interview process? The illusion of objectivity in
      phenomenological data generation.
AB  - This paper challenges the idea of researcher objectivity as a necessary feature
      of phenomenological interviewing by contrasting the philosophies of Husserl and
      Heidegger in relation to the way they influence the interview process, the
      generation of data and the role of the researcher in the interview. The
      discussion demonstrates how a failure to distinguish between Husserlian
      transcendental phenomenology and Heideggerian hermeneutic phenomenology results
      in methodological confusion. The interviewing process is analysed with regard to
      researchers' preconceptions, interviewer bias, the pursuit of objectivity and the
      relevance of subjectivity in phenomenological research. Quality indicators, such
      as adequacy of description and the elucidation of researchers' preconceptions,
      are discussed and illustrated with examples from the authors' doctoral studies.

PMID- 11470106
TI  - Teachers' understanding of facilitation styles with student nurses.
AB  - The notion of reflective, problem-based and experiential learning has become a
      significant phenomenon within nurse education. This paper will explore the
      general philosophies that seem to influence the interactional competences
      employed by 20 nurse teachers teaching pre-registration student nurses human
      skills. A qualitative approach was adopted using the in-depth interview for data
      collection. The intention was to emphasise the four types of teacher that emerged
      from the data, ranging from type 1, who displayed a striking negative attitude
      towards interpersonal skills work, to type 4, who was creative and enthusiastic.
      The major characteristics in the different types will be outlined in this paper.
      For the purpose of discussion, factors that influence the learning climate will
      be addressed and the implications for nurse education and study limitations will
      be considered.

PMID- 11470108
TI  - Model-based Roentgen stereophotogrammetry of orthopaedic implants.
AB  - Attaching tantalum markers to prostheses for Roentgen stereophotogrammetry (RSA)
      may be difficult and is sometimes even impossible. In this study, a model-based
      RSA method that avoids the attachment of markers to prostheses is presented and
      validated. This model-based RSA method uses a triangulated surface model of the
      implant. A projected contour of this model is calculated and this calculated
      model contour is matched onto the detected contour of the actual implant in the
      RSA radiograph. The difference between the two contours is minimized by variation
      of the position and orientation of the model. When a minimal difference between
      the contours is found, an optimal position and orientation of the model has been
      obtained. The method was validated by means of a phantom experiment. Three
      prosthesis components were used in this experiment: the femoral and tibial
      component of an Interax total knee prosthesis (Stryker Howmedica Osteonics Corp.,
      Rutherfort, USA) and the femoral component of a Profix total knee prosthesis
      (Smith & Nephew, Memphis, USA). For the prosthesis components used in this study,
      the accuracy of the model-based method is lower than the accuracy of traditional
      RSA. For the Interax femoral and tibial components, significant dimensional
      tolerances were found that were probably caused by the casting process and manual
      polishing of the components surfaces. The largest standard deviation for any
      translation was 0.19mm and for any rotation it was 0.52 degrees. For the Profix
      femoral component that had no large dimensional tolerances, the largest standard
      deviation for any translation was 0.22mm and for any rotation it was 0.22
      degrees. From this study we may conclude that the accuracy of the current model
      based RSA method is sensitive to dimensional tolerances of the implant. Research
      is now being conducted to make model-based RSA less sensitive to dimensional
      tolerances and thereby improving its accuracy.

PMID- 11470109
TI  - Pre-clinical validation of a new partially cemented femoral prosthesis by
      synergetic use of numerical and experimental methods.
AB  - The present work reports the pre-clinical validation of an innovative partially
      cemented femoral prosthesis called cement-locked uncemented (CLU) prosthesis. The
      inventors of the device under investigation claimed that, when compared to a
      comparable fully cemented stem, the new stem would present various advantages.
      Two previous experimental studies confirmed that primary stability and stress
      shielding were comparable to those of cemented stems. Aim of the present study
      was to investigate if the remaining claims were confirmed as well. A complete
      finite element model of the bone-implant complex was created from CT data. The
      model was validated against in vitro measurements of bone surface strains as well
      as against primary stability measurements. The peak stresses predicted in the CLU
      cement mantle were not found significantly lower than those reported in other
      studies on fully cemented stems. However, once the cement inlet geometry is
      optimised and the associated stress risers are eliminated, the CLU cement mantle
      should be subjected to much lower stresses. The stress induced in the stems by
      both load cases was well below the fatigue limit of the Ti6Al4V alloy. Finite
      element models predicted for all load cases relative motion between cement and
      metal lower than 60 microm. This amplitude may be fully accommodated by elastic
      deformations of the cement micro-ridges. The experimental and numerical results
      showed the validity of the new fixation concept, although a further optimisation
      of the geometry of the cement pockets is needed in order to further reduce the
      stresses in the cement.

PMID- 11470110
TI  - Lumbar spinal muscle activation synergies predicted by multi-criteria cost
      function.
AB  - The hypothesis that control of lumbar spinal muscle synergies is biomechanically
      optimized was studied by comparing EMG data with an analytical model with a multi
      component cost function that could include (1) trunk displacements, (2)
      intervertebral displacements, (3) intervertebral forces; (4) sum of cubed muscle
      stresses, and (5) eigenvalues for the first two spinal buckling modes. The
      model's independent variables were 180 muscle forces. The 36 displacements of 6
      vertebrae were calculated from muscle forces and the spinal stiffness. Calculated
      muscle activation was compared with EMG data from 14 healthy human subjects who
      performed isometric voluntary ramped maximum efforts at angles of 0 degrees, 45
      degrees, 90 degrees, 135 degrees and 180 degrees to the right from the anterior
      direction. Muscle activation at each angle was quantified as the linear
      regression slope of the RMS EMG versus external force relationship, normalized by
      the maximum observed EMG.There was good agreement between the analytical model
      and EMG data for the dorsal muscles when the model included either minimization
      of intervertebral displacements or minimization of intervertebral forces in its
      cost function, but the model did not predict a realistic level of abdominal
      muscles activation. Agreement with EMG data was improved with the sum of the
      cubed muscle stresses added to the cost function. Addition of a cost function
      component to maximize the trunk stability produced higher levels of antagonistic
      muscle activation at low efforts than at greater efforts. It was concluded that
      the muscle activation strategy efficiently limits intervertebral forces and
      displacements, and that costs of higher muscle stresses are taken into account,
      but stability does not appear to be maximized. Trunk muscles are apparently not
      controlled solely to optimize any one of the biomechanical costs considered here.

PMID- 11470111
TI  - A control theoretic model of the forearm.
AB  - In this paper, a control theoretic model of the forearm is developed and
      analyzed, and a computational method for predicting muscle activations necessary
      to generate specified motions is described. A detailed geometric model of the
      forearm kinematics, including the carrying angle and models of how the biceps and
      the supinator tendons wrap around the bones, is used. Also, including a dynamics
      model, the final model is a system of differential equations where the muscle
      activations play the role of control signals. Due to the large number of muscles,
      the problem of finding muscle activations is redundant, and this problem is
      solved by an optimization procedure. The computed muscle activations for
      ballistic movements clearly recaptures the triphasic ABC (Activation-Braking
      Clamping) pattern. It is also transparent, from the muscle activation patterns,
      how the muscles cooperate and counteract in order to accomplish desired motions.
      A comparison with previously reported experimental data is included and the model
      predictions can be seen to be partially in agreement with the experimental data.

PMID- 11470112
TI  - Simulation analysis of muscle activity changes with altered body orientations
      during pedaling.
AB  - Testing hypotheses related to the effect of gravitational orientation on neural
      control mechanisms is difficult for most locomotor tasks, like walking, because
      body orientation with respect to gravity affects both sensorimotor control and
      task mechanics. To examine the mechanical effect of body orientation
      independently from changes in workload and posture, Brown et al. (J. Biomech. 29
      p. 1349, 1996) studied pedaling at altered body orientations. They found that
      subjects pedaling at different orientations changed needlessly their muscle
      excitations, putatively to preserve body-upright pedaling kinematics. We tested
      the feasibility of this hypothesis using simulations based on a three
      biomechanical-function pair organization for control of lower limb muscles (limb
      extension/flexion pair, extension/flexion transition pair, and foot
      plantarflexion/dorsiflexion pair), where each pair consists of alternating
      agonistic/antagonistic muscles. Adjustment of only three parameters, one to scale
      the muscle excitations of each pair, was sufficient to preserve pedaling
      kinematics to altered body orientation. Because these adjustments produced
      changes in muscle excitation and net joint moments similar to those observed in
      pedaling subjects, the hypothesis is supported. Moreover, the effectiveness of a
      decoupled gain adjustment procedure where each parameter was adjusted by error in
      only one aspect of the pedaling trajectory during each iteration (i.e., cadence
      adjusted the Ext/Flex parameter; peak-to-peak variation in crank velocity over
      the cycle adjusted the transition parameter; average ankle angle over the cycle
      adjusted the foot parameter) further supports the distinct function of each
      muscle pair.

PMID- 11470113
TI  - Cortical bone tissue resists fatigue fracture by deceleration and arrest of
      microcrack growth.
AB  - Knowledge of kinetics of fatigue crack growth of microcracks is important so as
      to understand the dynamics of bone adaptation, remodeling, and the etiology of
      fatigue-based failures of cortical bone tissue. In this respect, theoretical
      models (Taylor, J. Biomech., 31 (1998) 587-592; Taylor and Prendergast, Proc.
      Instn. Mech. Engrs. Part H 211 (1997) 369-375) of microcrack growth in cortical
      bone have predicted a decreasing microcrack growth rate with increasing
      microcrack length. However, these predictions have not been observed directly.
      This study investigated microcrack growth and arrest through observations of
      surface microcracks during cyclic loading (R=0.1, 50-80MPa) of human femoral
      cortical bone (male, n=4, age range: 37-40yr) utilizing a video microscopy
      system. The change in crack length and orientation of eight surface microcracks
      were measured with the number of fatigue cycles from four specimens. At the
      applied cyclic stresses, the microcracks propagated and arrested in generally
      less than 10,000 cycles. The fatigue crack growth rate of all microcracks
      decreased with increasing crack length following initial identification,
      consistent with theoretical predictions. The growth rate of the microcracks was
      observed to be in the range of 5x10(-5) to 5x10(-7)mmcycle(-1). In addition, many
      of the microcracks were observed not to grow beyond 150 microm and a cyclic
      stress intensity factor of 0.5MNm(-3/2). The results of this study suggest that
      cortical bone tissue may resist fracture at the microscale by deceleration of
      fatigue crack growth and arrest of microcracks.

PMID- 11470114
TI  - Theoretical analysis of shape transformation of V-79 cells after treatment with
      cytochalasin B.
AB  - We observed that after treatment of V-79 fibroblasts with cytochalasin B the area
      of cell contact with the substrate is essentially reduced, the microtubules are
      organized into rodlike structures and the actin filaments are disintegrated.
      Remnants of the actin cortex become concentrated in the form of discrete patches
      under the plasma membrane. The described changes in the organization of the
      cytoskeleton and of the cortical shell are accompanied by the formation of a cell
      shape resembling the Greek letter phi. We calculated that the phi shape
      corresponds to the minimum of the stretching energy of the cortical shell at
      relevant geometrical constraints. In line with this result, if cytochalasin B
      treatment was followed by colchicine application which disrupted the microtubular
      rod, the characteristic phi shape completely disappeared. This study suggests
      that the effect of the microtubular rod on the cell shape can be theoretically
      well described by taking into account some basic conditions for the mechanical
      equilibrium of the cell cortical shell and the appropriate geometrical
      constraints.

PMID- 11470115
TI  - Structural properties of a new design of composite replicate femurs and tibias.
AB  - The purpose of this study was to compare the structural properties of a new vs.
      established design of composite replicate femurs and tibias. The new design has a
      cortical bone analog consisting of short-glass-fiber-reinforced (SGFR) epoxy,
      rather than the fiberglass-fabric-reinforced (FFR) epoxy in the currently
      available design. The hypothesis was that this new cortical bone analog would
      improve the uniformity of structural properties between specimens, while having
      mean stiffness values in the range of natural human bones. The composite
      replicate bones were tested under bending, axial, and torsional loads. In
      general, the new SGFR bones were significantly less stiff than the FFR bones,
      although both bone designs reasonably approximated the structural stiffnesses of
      natural human bones. With the exceptions of the FFR bone axial tests, the highest
      variability between specimens was 6.1%. The new SGFR bones had similar
      variability in structural properties when compared to the FFR bones under bending
      and torsional loading, but had significantly less variability under axial
      loading. Differences in epiphyseal geometry between the FFR and SGFR bones, and
      subsequent seating in the testing fixtures, may account for some of the
      differences in structural properties; axial stiffness was especially dependent on
      bone alignment. Stiffness variabilities for the composite replicate bones were
      much smaller than those seen with natural human bones. Axial strain distribution
      along the proximal-medial SGFR femur had a similar shape to what was observed on
      natural human femurs by other investigators, but was considerably less stiff in
      the more proximal locations.

PMID- 11470116
TI  - Analysis of human abnormal walking using zero moment joint: required compensatory
      actions.
AB  - This paper presents a multi-body model which can simulate human normal and
      abnormal walking. The abnormal walking model has a zero moment joint, abbreviated
      as ZMJ, representing a diseased joint of one leg. The joint can transmit a force
      to adjacent connected bodies, but cannot generate a moment about the joint to
      control motions of the bodies. Thus the ZMJ can be considered an extreme case of
      the diseased joint. Compensatory actions are required to make up for the lost
      function at the ZMJ in different patterns of variables, such as moments at sound
      joints, motions of upper torso, and so on. The characteristics of the abnormal
      walking having the ZMJ at the hip joint became so pronounced that the model could
      not walk in a realistic manner, not the case in the ZMJ at the knee.

PMID- 11470117
TI  - Method of determination of three dimensional index finger moment arms and tendon
      lines of action using high resolution MRI scans.
AB  - High-resolution MRI scans, in conjunction with CAD software, were used to
      determine the three-dimensional moment arms and force vector direction cosines
      for 11 structures passing the interphalangeal and metacarpophalangeal joints of
      the index finger. The results are presented for five different angles of joint
      flexion for a single subject. The moment arm data obtained differ from previous
      studies, where results have been derived from tendon excursion techniques or
      geometrical models. These dissimilarities have been accounted for by the
      differences in experimental techniques.

PMID- 11470118
TI  - Mechanical properties of cancellous bone in the human mandibular condyle are
      anisotropic.
AB  - The objective of the present study was (1) to test the hypothesis that the
      elastic and failure properties of the cancellous bone of the mandibular condyle
      depend on the loading direction, and (2) to relate these properties to bone
      density parameters. Uniaxial compression tests were performed on cylindrical
      specimens (n=47) obtained from the condyles of 24 embalmed cadavers. Two loading
      directions were examined, i.e., a direction coinciding with the predominant
      orientation of the plate-like trabeculae (axial loading) and a direction
      perpendicular to the plate-like trabeculae (transverse loading). Archimedes'
      principle was applied to determine bone density parameters. The cancellous bone
      was in axial loading 3.4 times stiffer and 2.8 times stronger upon failure than
      in transverse loading. High coefficients of correlation were found among the
      various mechanical properties and between them and the apparent density and
      volume fraction. The anisotropic mechanical properties can possibly be considered
      as a mechanical adaptation to the loading of the condyle in vivo.

PMID- 11470119
TI  - Mobility of the subtalar joint in the intact ankle complex.
AB  - A previous study by these authors showed that the calcaneus follows a unique path
      of unresisted coupled motion relative to the tibia during passive flexion and
      that most of this motion occurred at the ankle level. Subtalar motion in the
      intact ankle complex was observed only when perturbations from this path were
      induced by the application of force to the calcaneus. Relative motion of the
      bones of the ankle complex was tracked by stereophotogrammetry in seven
      specimens. Anatomical landmarks, reference frames and joint angles were defined
      by standard techniques. Sequential moments were applied to the calcaneus about
      the long axis of the tibia. Measured movements at subtalar level demonstrated
      plantarflexion coupled to supination and internal rotation (inversion) and
      dorsiflexion coupled to pronation and external rotation (eversion). These
      movements were resisted and were fully recovered when the external load was
      removed. Subtalar motion diminished as the ankle approached maximal dorsi- and
      plantarflexion. Two clearly distinguished mean axes of rotation were observed for
      inversion and eversion runs. The axes of inversion and eversion of the subtalar
      complex changed orientation along a preferred and repeatable path. The subtalar
      joint complex occupied only a single stable position in the unloaded state and
      with no range of unresisted motion. It is inferred that mobility was possible
      only by the stretching and lengthening of the ligaments and the indentation of
      the articular surfaces, requiring the application of loads. The subtalar joint
      complex behaves like a flexible structure.

PMID- 11470120
TI  - A physical model for simulating fusion of impaction-grafted morselized cancellous
      bone.
AB  - This article describes a method to simulate fusion of morselized cancellous bone.
      The morselized cancellous bone is mixed with an epoxy adhesive, in empirically
      determined proportions. The mixture is then impacted into a construct. When the
      epoxy cures, the morselized material fuses into a cohesive, contiguous structure
      with a compressive modulus equivalent to that of intact cancellous bone. This
      model can be used to study biomechanical aspects of fused impaction grafts.

PMID- 11470121
TI  - Merging of intersecting triangulations for finite element modeling.
AB  - Surface mesh generation over intersecting triangulations is a problem common to
      many branches of biomechanics. A new strategy for merging intersecting
      triangulations is described. The basis of the method is that object surfaces are
      represented as the zero-level iso-surface of the distance-to-surface function
      defined on a background grid. Thus, the triangulation of intersecting objects
      reduces to the extraction of an iso-surface from an unstructured grid. In a first
      step, a regular background mesh is constructed. For each point of the background
      grid, the closest distance to the surface of each object is computed. Background
      points are then classified as external or internal by checking the direction of
      the surface normal at the closest location and assigned a positive or negative
      distance, respectively. Finally, the zero-level iso-surface is constructed. This
      is the final triangulation of the intersecting objects. The overall accuracy is
      enhanced by adaptive refinement of the background grid elements. The resulting
      surface models are used as support surfaces to generate three-dimensional grids
      for finite element analysis. The algorithms are demonstrated by merging arterial
      branches independently reconstructed from contrast-enhanced magnetic resonance
      images and by adding extra features such as vascular stents. Although the
      methodology is presented in the context of finite element analysis of blood flow,
      the algorithms are general and can be applied in other areas as well.

PMID- 11470122
TI  - Assessment of inertial and gravitational inputs to the vestibular system.
AB  - A new device for the assessment of instantaneous angular and linear accelerations
      of the head is presented, which is based on four linear tri-axial accelerometers
      suitably attached to the head by an helmet. A procedure for reproducible helmet
      placement and calibration is given. A method is also illustrated to work out the
      different linear accelerations sensed by the vestibular organs in the left and
      right labyrinths and the components of the angular acceleration sensed by their
      semicircular canals. The computation is based on few individual parameters
      describing the helmet position with respect to external landmarks and on the
      average internal position and orientation of the vestibula. The purpose is to
      study the components of internal inertial forces, which represent the primary
      inputs to the vestibular system devoted to equilibrium and oculomotor control.
      The system is designed to be of easy application during rehabilitation exercises
      and in clinical environment during diagnostic and therapeutic manoeuvres. The
      prototype is tested with simple free movements such as "yes", "no", and gait.

PMID- 11470123
TI  - Is the behaviour of the leg during oscillation linear?
AB  - The linear behaviour of the human leg was studied using a free oscillation
      method. The lower leg is represented by a simple mass, spring and dashpot model.
      Forty-five subjects underwent free vibration tests on their right legs. The force
      amplitude and the time period, for successive oscillations enabled calculation of
      the stiffness to mass ratio values. It was found that the time period of the
      second oscillation cycle was significantly lower than that of the first, implying
      a corresponding increase in stiffness. The experimental data consistently
      exhibits these non-linear characteristics, indicating that the use of non-linear
      models could be of benefit for future free oscillation studies.

PMID- 11470124
TI  - New horizons in biogerontology: from molecules to humans. Proceedings of 2nd
      European Congress on Biogerontology, Saint-Petersburg, Russia, 25-28 August 2000.

PMID- 11470125
TI  - Replicative mosaicism might explain the seeming contradictions in the telomere
      theory of aging.
AB  - All living organisms are regarded as a mosaic of cells with different replicative
      histories explaining all the contradictions in the telomere theory of aging.
      Exhausted proliferative potential of cells in some areas of the organ tissue
      might be sufficient to promote one of the age-dependent diseases. Thus a
      combination of these disorders, gradually increasing with age, is aging. Nobody
      dies because of the age. Nothing other than the age-related diseases occur with
      age, and if we separate these diseases, we will get not just a healthy old man,
      but according to Dr Hayflick's new hypothesis (Exp. Gerontol., 33 (1998) 639) a
      healthy young man, if not a newborn child.

PMID- 11470126
TI  - Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly
      Longitudinal Free-living Ageing Study (BELFAST).
AB  - The ApoE gene has three alleles coding for the proteins apoE2, apoE3 and apoE4.
      E4 has been reported to be associated with hypercholesteraemia, ischaemic heart
      disease, age-related cognitive decline and Alzheimer's disease. Conversely, the
      E2 allele has been associated with longevity in French centenarians and their
      siblings. In this study, we have assessed any shift in the ApoE genotypes in
      nonagenarian subjects from Belfast where there is a high intrinsic incidence of
      cardiovascular disease. ApoE phenotypes were determined by electrofocusing and
      immunoblotting in 114 Senieur-approximated subjects >90 years old and compared
      with 2071 subjects, 30--65 years of age, recruited from the same geographical
      area by the MONItoring of CArdiovascular trends study group in Belfast (MONICA).
      The E4 allele was reduced in the nonagenarian group (X(2)=11.1; P=0.0006), the E3
      unchanged and E2 frequency was increased (X(2)=4.0; P=0.047). These results
      suggest that longevity is negatively associated with the E4 allele and may be
      associated with carriage of E2.

PMID- 11470127
TI  - An investigation of the age-dependency of chromosome abnormalities in human
      populations exposed to low-dose ionising radiation.
AB  - Among various cytogenetic changes stable chromosome aberrations (SCHA) seem to be
      the most significant for ageing and carcinogenesis. Being nonlethal they can
      persist through cell divisions and accumulate in time. We studied the age
      response of SCHA (translocations and insertions) in normal and radiation exposed
      human populations. Two cohorts of people at the age range of 3--72 years were
      studied: control (43 persons) and exposed to low doses of accidental irradiation
      due to Chernobyl accident and atomic bomb testing in Semipalatinsk (67 persons).
      FISH method was used for visualisation of chromosome aberrations. Metaphases from
      cultured lymphocytes were hybridised with biotinilated whole chromosome specific
      DNA probes for 1, 4 and 12 chromosomes, and with pancentromeric probe labelled
      with digoxigenin. The frequency of SCHA in lymphocytes increased as a quadratic
      function of donor age in both populations studied, being higher in exposed cohort
      as compared with control one. No age dependence for dicentrics was observed. The
      frequency of SCHA is a reliable biomarker of ageing in humans. Quadratic model of
      their age-response gives reasons to suggest that their increase is due to lower
      level of DNA repair or/and the genomic instability in older people. The exposure
      of people to low doses of ionising radiation accelerates the age-related increase
      of SCHA frequency.

PMID- 11470128
TI  - Different IL-8 production by T and NK lymphocytes in elderly subjects.
AB  - A gradual decline in the functional activity of the immune system is described
      with advancing age. The adaptive immune system seems the most severely affected,
      but some age-associated modifications also occurs in NK cells. Several studies
      investigated the age related changes of cytokine production, while little is
      known about chemokines, whose importance in regulating immune-response becomes
      even more evident. In this study we investigated whether the ability of T
      lymphocytes and NK cells to produce IL-8, either spontaneously or after
      activation, respectively with anti-CD3 monoclonal antibody or interleukin 2 (IL
      2) was affected by age. We demonstrated that: (a) T lymphocytes and NK cells
      spontaneously produced detectable amounts of IL-8; (b) anti-CD3 stimulation of T
      lymphocytes significantly increased IL-8 production and the increment was more
      evident in the nonagenarian subjects; (c) similarly, IL-2 stimulation of NK cells
      rose the production of IL-8 but the amount produced by the old was lower than the
      one produced by the young group. Because of the co-stimulatory role of chemokines
      on NK responses and given the demonstrated importance of NK cells in defence
      against viral infections, the decreased production of IL-8 can be involved in the
      defective functional activity of NK cells from old subjects.

PMID- 11470129
TI  - Aging impairs intestinal immunity.
AB  - The elderly are characterized by immunosenescence accompanied by high rates of
      morbidity and mortality associated with infectious diseases. Despite suggestions
      that the mucosal immune compartment is relatively unaffected by aging, there are
      marked deficits in the intestinal mucosal immune responses of old animals and
      elderly humans. Little is known about the mechanism(s) whereby aging disrupts
      intestinal immunity. However, several events in the genesis of the intestinal
      immune response may be perturbed during aging. The first step is the uptake of
      antigens by specialized epithelial cells (M cells) that overlie the domes of
      Peyer's patches. We are unaware of any studies on the efficacy of antigen uptake
      in the intestine as a function of age. The effects of aging on the next step,
      antigen presentation by dendritic cells and lymphocyte isotype switching, have
      not been resolved. The third event is the maturation of immunoglobulin A (IgA)
      immunoblasts and their migration from the Peyer's patches to the intestinal
      mucosa. Quantitative immunohistochemical analyses suggest that the migration of
      these putative plasma cells to the intestinal effector site is compromised in old
      animals. Local antibody production by mature IgA plasma cells in the intestinal
      mucosa constitutes the fourth step. We recently reported that in vitro IgA
      antibody secretion by intestinal lamina propria lymphocytes from young and
      senescent rats is equivalent. The last event is the transport of IgA antibodies
      across the epithelial cells via receptor-mediated vesicular translocation onto
      the mucosal surface of the intestine. Receptor-binding assays did not detect age
      associated declines in receptor number or binding affinity in either rodent or
      primate enterocytes as a function of donor age. Efforts to identify the
      mechanism(s) responsible for the age-related decline in intestinal mucosal immune
      responsiveness may benefit by focusing on the homing of IgA immunoblasts to the
      effector site.

PMID- 11470130
TI  - Cyclodextrin modulation of T lymphocyte signal transduction with aging.
AB  - There is an alteration of the immune response in aging that leads to the
      increased incidence of infections, cancers and autoimmune disorders. The aim of
      the present study was to investigate whether there exists changes in signal
      transduction under the IL-2 receptor stimulation and the role of plasma membrane
      cholesterol in the activation of T cells with aging. We report age-related
      changes in the JAK-STAT signalling pathway that results in decreased tyrosine
      phosphorylation of STAT5. We present evidence for the importance of cholesterol
      content in regulating signalling pathways in T cells and in modulating their
      proliferation by using the plasma membrane cholesterol-depleting agent methyl
      beta-cyclodexrin (MBCD). MBCD treatment (0.5 mM) induced a significant decrease
      in the cholesterol content of T cells of elderly subjects whereas it was
      increased in T cells of young subjects. MBCD induced changes in the
      phosphorylation of p56(lck), especially in T cells of elderly subjects. The
      proliferation of MBCD-treated T cells decreased in lymphocytes of young subjects
      but did not change in T cells of elderly subjects. These results suggest a role
      for plasma membrane cholesterol in the regulation of the TcR signalling pathways
      with differential effects related to aging. However, the data suggest that
      modulation of the plasma membrane cholesterol content alone may not be enough to
      restore signal transduction changes with aging.

PMID- 11470131
TI  - Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein
      carbonyl groups.
AB  - Carnosine (beta-alanyl-L-histidine) is a physiological dipeptide which can delay
      ageing and rejuvenate senescent cultured human fibroblasts. Carnosine's anti
      oxidant, free radical- and metal ion-scavenging activities cannot adequately
      explain these effects. Previous studies showed that carnosine reacts with small
      carbonyl compounds (aldehydes and ketones) and protects macromolecules against
      their cross-linking actions. Ageing is associated with accumulation of carbonyl
      groups on proteins. We consider here whether carnosine reacts with protein
      carbonyl groups. Our evidence indicates that carnosine can react non-enzymically
      with protein carbonyl groups, a process termed 'carnosinylation'. We propose that
      similar reactions could occur in cultured fibroblasts and in vivo. A preliminary
      experiment suggesting that carnosine is effective in vivo is presented; it
      suppressed diabetes-associated increase in blood pressure in fructose-fed rats,
      an observation consistent with carnosine's anti-glycating actions. We speculate
      that: (i) carnosine's apparent anti-ageing actions result, partly, from its
      ability to react with carbonyl groups on glycated/oxidised proteins and other
      molecules; (ii) this reaction, termed 'carnosinylation,' inhibits cross-linking
      of glycoxidised proteins to normal macromolecules; and (iii) carnosinylation
      could affect the fate of glycoxidised polypeptides.

PMID- 11470132
TI  - How individual age-associated changes may influence human morbidity and mortality
      patterns.
AB  - Patterns of human mortality share common traits in different populations. They
      include higher mortality in early childhood, lower mortality during the
      reproductive period, an accelerated increase of mortality near the end of the
      reproductive period, and deceleration in the mortality increase at oldest old
      ages. The deceleration of mortality rate is one of the most intriguing recent
      findings in longevity research. The role of differential selection in this
      phenomenon has been well studied. Possible contribution of individual aging in
      the shape of mortality curve is also recognized. However, this contribution has
      not been studied in details. In this paper, we specify most common patterns of
      age-associated changes in an individual organism and discuss their possible
      influence on morbidity and mortality in population. We subdivide individual age
      associated changes into three components, having different influence on morbidity
      and mortality: (1) basal, (2) ontogenetic, and (3) time-dependent. Basal changes
      are connected with the universal decrease in the rate of living during an
      individual life. As a result, some phenotypic effects of aging may accumulate in
      an organism at a slower rate with age. Basal changes are likely to contribute to
      a plateau of morbidity often observed at old ages, and may partially be
      responsible for mortality deceleration at oldest old ages. Ontogenetic component
      is connected with change of the stages of ontogenesis (e.g., the growth, the
      reproductive period and the climacteric) during an individual life. The
      ontogenesis-related changes contribute to wave-like patterns of morbidity in
      population and may partially be responsible for mortality increase at middle ages
      and its deceleration at old ages. Time-dependent changes are connected with long
      time exposure of an organism to different harmful factors. They are most likely
      to contribute to morbidity and mortality acceleration. We discuss how all three
      components of individual age-associated changes may interact in human organism
      and influence patterns of morbidity and mortality in population.

PMID- 11470133
TI  - Use of mathematical models of survivorship in the study of biomarkers of aging:
      the role of heterogeneity.
AB  - An ever increasing number of people have been engaging in aging research using
      various interventions aimed to modify aging processes, and/or life span, of
      experimental animals. Since this type of studies needs outcome parameters for
      assessing the efficacy of such interventions, research on biomarkers of aging
      (ABs) has received new stimuli. In the present paper, the problem of the
      occurrence of a vicious circle any time we study ABs and determinants of aging is
      addressed. In fact, while ABs would represent the standard reference to be used
      in the study of the main causes of processes of aging, these very determinants
      should already be known in order to get reliable ABs. A feasible way to overcome
      this impasse is proposed, using mathematical models of survivorship or mortality
      based on biological hypotheses and accounting for inter-individual heterogeneity,
      a necessary ingredient for a correct interpretation of survival results. Specific
      kinetics of experimental parameters that are candidates as ABs can be compared to
      the kinetics hypothesized for general biological functions entering the model. We
      have built a model of this type that can also be used to perform a reliable
      overall gross estimate of the rate of aging, R(a), in the population, a parameter
      useful when judging the success of interventions aimed to act on determinants of
      aging. The perspective that theory of complex systems can be of help in the
      search for ABs is also discussed.

PMID- 11470134
TI  - Ageing and survival after different doses of heat shock: the results of analysis
      of data from stress experiments with the nematode worm Caenorhabditis elegans.
AB  - Stress experiments performed on a population of sterilised nematode worms
      (Caenorhabditis elegans) show a clear hormesis effect after short exposure and
      clear debilitation effects after long exposure to heat shock. An intermediate
      duration of exposure results in a mixture of these two effects. In this latter
      case the survival curves for populations in the stress and control groups
      intersect. In this paper we develop an adaptation model of stress and apply it to
      the analysis of survival data from three such stress experiments. We show that
      the model can be used to explain empirical age-patterns of mortality and survival
      observed in these experiments. We discuss possible biological mechanisms involved
      in stress response and directions for further research.

PMID- 11470137
TI  - The Future of Molecular Medicine. 4th Berlin Colloquium of the Gottlieb Daimler
      and Karl Benz Foundation in co-operation with the Max Delbruck Center for
      Molecular Medicine (MDC), Berlin-Buch, on Wednesday, May 10, 2000 in Berlin at
      the Konrad Adenauer foundation, Tiergartenstr. 35, D-10785 Berlin.

PMID- 11470138
TI  - The future of genomics.

PMID- 11470139
TI  - The future of human gene therapy.
AB  - Human gene therapy (HGT) is defined as the transfer of nucleic acids (DNA) to
      somatic cells of a patient which results in a therapeutic effect, by either
      correcting genetic defects or by overexpressing proteins that are therapeutically
      useful. In the past, both the professional and the lay community had high
      (sometimes unreasonably high) expectations from HGT because of the early promise
      of treating or preventing diseases effectively and safely by this new technology.
      Although the theoretical advantages of HGT are undisputable, so far HGT has not
      delivered the promised results: convincing clinical efficacy could not be
      demonstrated yet in most of the trials conducted so far, while safety concerns
      were raised recently as the consequence of the "Gelsinger Case" in Philadelphia.
      This situation resulted from the by now well-recognized disparity between theory
      and practice. In other words, the existing technologies could not meet the
      practical needs of clinically successful HGT so far. However, over the past
      years, significant progress was made in various enabling technologies, in the
      molecular understanding of diseases and the manufacturing of vectors. HGT is a
      complex process, involving multiple steps in the human body (delivery to organs,
      tissue targeting, cellular trafficking, regulation of gene expression level and
      duration, biological activity of therapeutic protein, safety of the vector and
      gene product, to name just a few) most of which are not completely understood.
      The prerequisite of successful HGT include therapeutically suitable genes (with a
      proven role in pathophysiology of the disease), appropriate gene delivery systems
      (e.g., viral and non-viral vectors), proof of principle of efficacy and safety in
      appropriate preclinical models and suitable manufacturing and analytical
      processes to provide well-defined HGT products for clinical investigations. The
      most promising areas for gene therapy today are hemophilias, for monogenic
      diseases, and cardiovascular diseases (more specifically, therapeutic
      angiogenesis for myocardial ischemia and peripheral vascular disease, restenosis,
      stent stenosis and bypass graft failure) among multigenic diseases. This is based
      on the relative ease of access of blood vessels for HGT, and also because
      existing gene delivery technologies may be sufficient to achieve effective and
      safe therapeutic benefits for some of these indications (transient gene
      expression in some but not all affected cells is required to achieve a
      therapeutic effect at relatively low [safe] dose of vectors). For other diseases
      (including cancer) further developments in gene delivery vectors and gene
      expression systems will be required. It is important to note, that there will not
      be a "universal vector" and each clinical indication may require a specific set
      of technical hurdles to overcome. These will include modification of viral
      vectors (to reduce immunogenicity, change tropism and increase cloning capacity),
      engineering of non-viral vectors by mimicking the beneficial properties of
      viruses, cell-based gene delivery technologies, and development of innovative
      gene expression regulation systems. The technical advances together with the ever
      increasing knowledge and experience in the field will undoubtedly lead to the
      realization of the full potential of HGT in the future.

PMID- 11470140
TI  - Stem cells. An introduction to the biology of an unclear promise.

PMID- 11470141
TI  - Potential of embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cell lines established from
      undifferentiated embryonic cells characterized by nearly unlimited self-renewal
      and differentiation capacity. During differentiation in vitro, ES cells were
      found to be able to develop into specialized somatic cells types and to
      recapitulate processes of early embryonic development. These properties allow to
      use ES cells as model system for studying early embryonic development by gain- or
      loss-of-function approaches, or to investigate the effects of drugs and
      environmental factors on differentiation and cell function in embryotoxicity and
      pharmacology. Now, ES cells derived of human blastocysts may be used for the
      generation of somatic precursor or differentiated cells in cell and tissue
      therapy. The review presents data of mouse ES cell differentiation and gives an
      outlook on future perspectives and problems of using human ES cells in
      regenerative medicine.

PMID- 11470142
TI  - Human pluripotent stem cells: NIH Guidelines.

PMID- 11470143
TI  - Neutrality and consensus: towards a viable policy on human stem cell research.

PMID- 11470144
TI  - Examination of oral sensitization with ovalbumin in Brown Norway rats and three
      strains of mice.
AB  - We studied the conditions needed to sensitize animals to the oral feeding of food
      allergens, without induction of tolerance, in order to investigate the
      allergenicity of orally ingested food proteins. Brown Norway (BN) rats were
      sensitized by daily OVA (ovalbumin)-gavage or by drinking OVA containing water ad
      libitum and the ASA (active systemic anaphylaxis) response, as the immediate
      hypersensitivity response to antigen stimulation after oral sensitization, was
      examined. The oral administration of OVA by gavage produced a higher OVA-specific
      IgE response and an increase in serum histamine after antigen challenge, as
      compared to those produced by drinking water. Next, we examined the effect of
      murine age, the oral feeding technique and the oral feeding dose on sensitization
      using BALB/c, B10A and ASK mice. Twenty-week-old mice showed the strongest OVA
      specific IgE and IgG1 responses and ASA-associated serum histamine contents
      increased with gavage in the three different age groups of BALB/c mice.
      Administering 0.1 mg of OVA by gavage daily for 9 weeks appeared to induce a
      higher response than administering 1 mg of OVA, in terms of OVA-specific IgE and
      IgG1 antibody responses and ASA responses. Among the three strains of mice, B10A
      mice exhibited the highest response in terms of OVA-specific IgE and IgG1
      antibody and ASA responses. These findings suggested BN rats and B10A mice were
      suitable models for oral sensitization with antigen protein and that oral
      sensitization in mice requires low dose, intermittent antigen intakes.

PMID- 11470145
TI  - The majority of lamina propria CD4(+) T-cells from scid mice with colitis undergo
      Fas-mediated apoptosis in vivo.
AB  - We have previously shown that adoptively transferred CD4(+) T-cells mediate an
      chronic colitis in severe combined immune deficient (scid) mice. Colitis is
      accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing
      CD4(+) T-cells in the diseased colonic lamina propria (Eur. J. Immunol. 28:3655
      (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina
      propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina
      propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a
      TCR/CD3 redirected chromium-release assay, but do not express TNF-alpha mediated
      cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with
      an anti-FasL antiserum partially blocked killing of the Fas transfected target
      cells, indicating a role for the Fas-FasL system in the killing process.
      Treatment of scid mice with colitis with anti-FasL antiserum for 12 h blocked the
      apoptotic process in lamina propria CD4(+) T-cells by more than 65% compared to
      mice treated with control antiserum. Together, these results point towards the
      Fas-FasL and not the TNF-alpha-TNF-alpha receptor system as the primary apoptosis
      inducing mechanism of lamina propria CD4(+) T-cells in this model of murine
      chronic colitis, and suggest an important role for the Fas-FasL system in the
      maintenance of homeostasis of locally proliferating T-cells.

PMID- 11470146
TI  - Immune response induced by immunization with Hepatitis B virus core DNA isolated
      from chronic active hepatitis patients.
AB  - There are many mutations in the gene encoding Hepatitis B virus (HBV) core
      antigen of chronic active hepatitis patients, and such mutations are most likely
      to be related to the severity of disease. Here, we constructed plasmids
      containing wild-type and deletion type of HBV core gene (HBc) to develop an
      experimental DNA vaccine and to compare immunogenicity of two types of HBc
      vaccine. Twenty-nine wild-types and seven deletion types of HBc were detected in
      sera of 32 Korean patients with chronic active hepatitis. Four wild-types (W1,
      W2, W4, W6) and two deletion types (D3, D4) of HBc were cloned into the pcDNA3
      vector. Intramuscular immunization with wild-type HBc efficiently increased serum
      anti-HBc antibody response in a dose-dependent manner. Anti-HBc antibody response
      in mice injected with W6 increased 14 days after immunization, and peaked after
      30 days and was maintained at least up to 50 days. W6 immunization induced a
      specific cytotoxic T lymphocyte response to W6-transfected 3LL (3LL-W6), and
      reduced the sizes of tumor mass of mice challenged with 3LL-W6 or 3LL transfected
      with D4. However, intramuscular immunization with D3 and D4 did not show antibody
      response at all. D3 and D4 have 157 bp (from 331 to 491 bp) and 122 bp (from 327
      to 448 bp) gene deletion, respectively, and these encode class II MHC-restricted
      T-cell epitope. Altogether, these results suggest that mutant virus that has
      deleted HBc gene may evade immune systems due to loss of T-cell epitope.

PMID- 11470147
TI  - Peripheral blood cell bulk cultures are not suitable for the analysis of the
      genetic control of T-cell cytokine function.
AB  - Recently evidence has been provided for a genetic control of T-cell dependent
      cytokine production by HLA-class II. Candidate genes in multiple sclerosis, a T
      cell mediated autoimmune disease, are the disease-associated DR2, DQ6, Dw2
      haplotype. Previous observations by us and others imply a HLA-DR2 dependent
      propensity of antigen-specific T-cell lines to produce increased amounts of TNF
      alpha/beta. Here, we tested a possible association between HLA or disease status
      with cytokine production employing the simple and widely used method of bulk
      cultures. Peripheral blood cells of 48 patients and 68 healthy individuals were
      analyzed. We observed no significant differences of the cytokine production in
      relation to disease status or any HLA polymorphism. Our data indicate that, in
      contrast to monoclonal T-cell cultures, bulk cultures are not suitable to detect
      immunogenetic control of T-cell function.

PMID- 11470148
TI  - Pharmacological evidence for complex and multiple site interaction of CXCR4 with
      SDF-1alpha: implications for development of selective CXCR4 antagonists.
AB  - The C-X-C chemokine SDF-1 and its receptor CXCR4, mediate a pivotal role in the
      pathophysiology of HIV-1 infection and vascular inflammatory diseases. In this
      study, we investigated the pharmacological properties of SDF-1alpha interaction
      with CXCR4 in human leukemia cell lines. Our data, based on [125I]-SDF-1alpha
      radioligand binding, SDF-1alpha-induced [35S]-GTPgammaS binding and use of
      specific CXCR4 antagonist AMD3100 reveals the complex nature of SDF-1alpha-CXCR4
      interaction. Firstly, homologous competition with cold SDF-1alpha revealed a
      bimodal ligand displacement curve and secondly, although AMD3100 inhibited both
      SDF-1alpha-mediated chemotaxis (IC(50)=4.7 nM) and [35S]-GTPgammaS binding
      (IC(50)=7.4 nM) with high affinity, it was intriguingly up to 3000-fold less
      potent (IC(50)=15.2 microM) in the radioligand binding assay. These results
      provide pharmacological evidence for the recently described two-site model for
      SDF-1alpha-CXCR4 interaction. Accordingly, inhibition of SDF-1alpha binding to
      one of the receptor sites is sufficient to antagonize function, without causing
      its complete displacement from the receptor. Furthermore, these findings have
      important implications in the development and evaluation of CXCR4-selective small
      molecule antagonists for therapeutic use.

PMID- 11470149
TI  - Three-color flow cytometric assay for the study of the mechanisms of cell
      mediated cytotoxicity.
AB  - Cytotoxic lymphocytes kill tumor or virus-infected target cells utilizing two
      mechanisms (1) release of lytic granules (containing perforin and granzymes) and
      (2) Fas ligand (FasL)/Fas or TNF initiated apoptosis. We have examined mechanisms
      of target cell lysis using a new Flow Cytometric Cytotoxicity Assay (FC Assay).
      Target cells were labeled with PKH 67 dye. Cell death was estimated by 7-amino
      actinomycin (7-AAD) inclusion and annexin V-PE binding. A strong direct
      correlation has been found between the percentage of dead target cells in the FC
      Assay and the results of 51Cr release assay when human LAK and CTL were used as a
      model system. We have shown that both NK and CTL kill tumor cells mostly by
      granule-mediated mechanisms, as lysis was blocked by a perforin inhibitor
      Concanamycin A (Folimycin) but was significantly less sensitive to zVAD-FMK
      caspase inhibition. The FC assay allows accurate measurement of cell-mediated
      cytotoxicity as individual target cell death is detected directly.

PMID- 11470150
TI  - Effect of interleukin 10 on the release of the CXC chemokines growth related
      oncogene GRO-alpha and epithelial cell-derived neutrophil activating peptide
      (ENA)-78 during human endotoxemia.
AB  - Pretreatment with interleukin (IL)-10 inhibited the release of growth-related
      oncogene GRO-alpha but not of epithelial-cell derived neutrophil activating
      protein (ENA)-78, after injection of lipopolysaccharide (LPS) into healthy
      humans. In vitro, IL-10 dose-dependently attenuated LPS-induced release of both
      GRO-alpha and ENA-78 in whole blood and in cultures of isolated polymorphonuclear
      and mononuclear cells.

PMID- 11470151
TI  - DNA polymerase beta is not essential for the formation of palindromic (P) region
      of T cell receptor gene.
AB  - Formation of palindromic (P) region at the variable (V)-diversity (D)-joining (J)
      junction in DNA polymerase beta (pol-beta) deficient mice were investigated by
      sequencing of reverse transcriptase-polymerase chain reaction (RT-PCR) products
      of mRNAs encoding the beta chain of T cell receptor (TCR). Total 42 and 43 cDNA
      clones encoding V(beta8)-D(beta)-J(beta)-C(beta) from E18.5 embryonic thymocytes
      of pol-beta gene knocked-out and wild type control mouse, respectively, were
      sequenced. Among them five and six clones from pol-beta knocked-out and wild
      type, respectively, have P insertions of two nucleotides. This result
      unequivocally indicates that pol-beta, which is one of the repair-type DNA
      polymerases most abundantly expressed in thymus and spleen, is not essential for
      the formation of P region.

PMID- 11470152
TI  - Type D retrovirus specific sequences in lymphocytes of the children with Burkitt
      type lymphoma and their parents.
AB  - Type D retroviruses cause immunodeficiency in monkey. Earlier we have revealed
      genetical and serological markers of type D retroviruses in children with Burkitt
      type lymphoma. Using PCR/Southern blotting assay we have found sequences related
      to MPMV in PBMC's DNA from children with Burkitt-type lymphoma and from their
      parents. Moreover, the data on sequencing of virus specific sequences from one
      ill child and from his mother have been presented.

PMID- 11470154
TI  - Characterization of two novel human small heat shock proteins: protein kinase
      related HspB8 and testis-specific HspB9.
AB  - Using search profiles based on the conserved alpha-crystallin domain that is
      characteristic for small heat shock proteins (sHsps), we traced two new human
      sHsps. One of these, being the eighth known human sHsp and thus named HspB8, was
      recently described as a serine-threonine protein kinase (H11), but not identified
      as an sHsp (C.C. Smith, Y.X. Yu, M. Kulka, L. Aurelian, J. Biol. Chem. 275
      (2000)). Northern blotting showed that HspB8/H11 is predominantly transcribed in
      skeletal muscle and heart, like most other sHsps. The other, named HspB9, is
      specifically expressed in testis, notably in the spermatogenic cells from late
      pachytene spermatocyte stage till elongate spermatid stage. While mammalian sHsps
      are generally highly conserved, mouse HspB9 shows 38% sequence difference with
      human HspB9, which may confirm its sex-related role.

PMID- 11470155
TI  - Mapping proteins of the 50S subunit from Escherichia coli ribosomes.
AB  - Mapping of protein positions in the ribosomal subunits was first achieved for the
      30S subunit by means of neutron scattering about 15 years ago. Since the 50S
      subunit is almost twice as large as the 30S subunit and consists of more
      proteins, it was difficult to apply classical contrast variation techniques for
      the localisation of the proteins. Polarisation dependent neutron scattering (spin
      contrast variation) helped to overcome this restriction. Here a map of 14
      proteins within the 50S subunit from Escherichia coli ribosomes is presented
      including the proteins L17 and L20 that are not present in archeal ribosomes. The
      results are compared with the recent crystallographic map of the 50S subunit from
      the archea Haloarcula marismortui.

PMID- 11470156
TI  - Identification of highly conserved genes: SNZ and SNO in the marine sponge
      Suberites domuncula: their gene structure and promoter activity in mammalian
      cells(1).
AB  - Recently, we reported that cells from the sponge Suberites domuncula respond to
      ethylene with an increase in intracellular Ca(2+) level [Ca(2+)](i), and with an
      upregulation of the expression of (at least) two genes, a Ca(2+)/calmodulin
      dependent protein kinase and the potential ethylene-responsive gene, termed
      SDSNZERR (A. Krasko, H.C. Schroder, S. Perovic, R. Steffen, M. Kruse, W.
      Reichert, I.M. Muller, W.E.G. Muller, J. Biol. Chem. 274 (1999)). Here, we
      describe for the first time that also mammalian (3T3) cells respond to ethylene,
      generated by ethephon, with an immediate and transient, strong increase in
      [Ca(2+)](i). Next, the promoter for the sponge SDSNZERR gene was isolated from S.
      domuncula. It was found that the SDSNZERR gene is positioned adjacent to the SNZ
      related gene (SNZ-proximal open reading frame) (SDSNO) and linked, as in
      Saccharomyces cerevisiae, in a head-to-head manner. Until now, neither homologues
      nor orthologues of these two genes have been identified in higher metazoan phyla.
      The full-length genes share a bidirectional promoter. 3T3 cells were transfected
      with this promoter; the activity of the SDSNZERR promoter was strong and twice as
      high as that of the SV40 promoter, while the SDSNO promoter was less active.
      Surprisingly, the activity of the SDSNZERR promoter could not be modulated by
      ethylene or salicylic acid while it is strongly upregulated, by 4-fold, under
      serum-starved conditions. It is concluded that the modulation of the level of
      [Ca(2+)](i) by ethylene in mammalian cells is not correlated with an upregulation
      of the ethylene-responsive gene SDSNZERR. The data indicate that in mammalian
      cells, the activity of the SDSNZERR promoter is associated with the repression of
      serum-mediated growth arrest.

PMID- 11470157
TI  - Molecular cloning, expression and evolution of the Japanese flounder goose-type
      lysozyme gene, and the lytic activity of its recombinant protein.
AB  - In this study, we cloned the goose-type (g-type) lysozyme gene from the Japanese
      flounder genomic DNA library, the first such data in fish and only the second
      after the chicken g-type lysozyme gene. The Japanese flounder g-type lysozyme
      gene was 1252 bp in length from the transcription site to the polyadenylation
      site, coded for 758 bp of mRNA and 195 deduced amino acids, which contain five
      exons and four introns. A phylogenetic analysis based on amino acid sequences
      showed that the flounder gene was closer to g-type lysozyme, followed by phage
      type lysozyme and then chicken-type (c-type) lysozyme. Although exon 1 of the
      flounder gene differs from exons 1 and 2 of the chicken g-type lysozyme gene,
      three catalytic residues, as well as their neighboring amino acids were conserved
      between the Japanese flounder and the four avian g-type lysozymes. In a Southern
      blot analysis using the genomic DNA of homo-cloned Japanese flounder, the
      flounder g-type lysozyme gene showed a simple pattern, suggesting that it is
      encoded by a single copy gene. A Northern blot analysis showed that this gene was
      expressed in all tissues of Japanese flounder that we examined in this study and
      showed major differences from those expressed tissues of the chicken g-type gene.
      Japanese flounder g-type lysozyme mRNA levels in the intestine, heart and whole
      blood increased after injecting the fish with Edwardsiella tarda. Recombinant
      flounder g-type lysozyme, which has an optimal pH and temperature of pH 6.0 and
      25 degrees C, possessed lytic activity against Micrococcus lysodeikticus and
      several fish pathogenic bacteria. This is the first report of a g-type lysozyme
      gene other than for reported avian species.

PMID- 11470158
TI  - Molecular cloning and functional expression analysis of a cDNA for human
      hepassocin, a liver-specific protein with hepatocyte mitogenic activity.
AB  - By means of differential cDNA expression cloning, we earlier isolated a novel rat
      cDNA and its protein, named hepassocin, which is upregulated during liver
      regeneration. Using the rat cDNA as a probe, we have now isolated human
      hepassocin cDNA encoding a protein of 312 amino acids, which has 81.4% and 83.8%
      identity, respectively, to rat hepassocin before and after elimination of its
      signal peptide. Dot blot analysis revealed that hepassocin mRNA was strongly
      expressed in adult liver, fairly strongly in fetal liver, and weakly in pancreas,
      but not in other tissues. Recombinant human hepassocin produced in Chinese
      hamster ovary (CHO) cells by the dihydrofolate reductase-methotrexate (DHFR--MTX)
      gene amplification method is a homodimer (68 kDa) and has mitogenic activities in
      hepatocytes of various animal species including rat, mouse, rabbit and dog, and
      the activity was lost with 2-mercaptoethanol treatment. These results suggest
      that hepassocin is a potent regulator in liver cell growth not only in rats but
      also in humans. Computer searches revealed that human hepassocin as well as rat
      hepassocin has a characteristic disulfide structure close to that of fibrinogen
      gamma. We assume that this newly identified growth factor exerts functions in
      association with an extracellular matrix such as fibrinogen.

PMID- 11470159
TI  - Identification of Dof proteins with implication in the gibberellin-regulated
      expression of a peptidase gene following the germination of rice grains.
AB  - Type III carboxypeptidase (CPD3) is one of the hydrolytic enzymes whose
      expression is up-regulated by gibberellins (GA) in the aleurones of germinated
      cereal grains. A number of pyrimidine boxes and a sequence resembling the
      gibberellic acid response element (GARE) are observed in the region upstream of
      the transcription initiation site of the CPD3 gene, showing a characteristic of
      cereal GA-responsive genes. Transient gene expression assays in germinated rice
      aleurone demonstrated that the CPD3 promoter was able to confer hormonally
      responses on the expression of the reporter gene. By southwestern screening,
      several cDNAs encoding the Dof class proteins were isolated from a rice aleurone
      library. Each mRNA accumulation for five novel members of Dof proteins (OsDof1-
      5) occurs with a different time course and in a tissue-specific manner following
      the germination of grains. Of these, the expression of the OsDof3 gene is
      abundant in aleurones where it precedes that of the CPD3 gene, implying that this
      is an early response gene of GA. The OsDof3 protein, expressed in Escherichia
      coli, selectively bound AAAG motifs of the pyrimidine boxes through the DNA
      binding activity of its Dof domain. Co-expression experiments in aleurones
      suggested that the OsDof3 protein should play a regulatory role in the expression
      of the CPD3 gene under the control of GA.

PMID- 11470160
TI  - In the facultative sulphate/nitrate reducer Desulfovibrio desulfuricans ATCC
      27774, the nine-haem cytochrome c is part of a membrane-bound redox complex
      mainly expressed in sulphate-grown cells.
AB  - The bacterium Desulfovibrio desulfuricans ATCC 27774 belongs to the group of
      sulphate reducers also capable of utilising nitrate as its terminal electron
      acceptor for anaerobic growth. One of the complex multihaem proteins found in
      nitrate- or sulphate-grown cells of Desulfovibrio desulfuricans ATCC 27774 is the
      nine-haem cytochrome c. The present work shows that the gene encoding for
      Desulfovibrio desulfuricans ATCC 27774 nine-haem cytochrome c is part of an
      operon formed by the gene cluster 9hcA-D. Besides 9hcA, the gene encoding for the
      nine-haem cytochrome c, genes 9hcB to D encode for a protein containing four [4Fe
      4S](2+/1+) centres, for a dihaem transmembrane cytochrome b and for an unknown
      hydrophobic protein, respectively. The four proteins have a predicted topology
      that is in accordance with the formation of a membrane-bound redox complex.
      Furthermore, the transcriptional studies show that not only the expression of the
      9HcA-D complex is dependent on the growth phase, but also is markedly increased
      in sulphate-grown cells.

PMID- 11470161
TI  - Molecular cloning of rabbit hyaluronic acid synthases and their expression
      patterns in synovial membrane and articular cartilage.
AB  - cDNAs for hyaluronic acid synthases (HAS2 and HAS3) were cloned from a cDNA
      library of cultured rabbit synovial membrane cells. The cDNA encoding the open
      reading frame of rabbit HAS2 and HAS3 was 1659 nucleotides in length with a
      predicted molecular mass of about 63 kDa. The amino acid sequence showed that the
      rabbit HAS2 was 98.7 and 98.4%, and HAS3 was 98.2 and 97.5% identical with human
      and mouse forms of the proteins, respectively. The predicted sequences for
      hyaluronic acid (HA) binding motifs and the catalytic domains related to beta 1-4
      and beta 1-3 linkages, essential for HA synthesis, were almost conserved in both
      rabbit HAS2 and HAS3, similarly to human and mouse HASs. RT-PCR analysis and in
      situ hybridization revealed that the mRNA of HAS2 was highly expressed in the
      synovial membrane and articular cartilage, whereas the expression of HAS3 mRNA
      was slightest in these tissues. Thus, it is demonstrated that rabbit HASs are
      highly conserved in sequence content as compared to the human and mouse
      homologues described previously, and that HAS2 is predominantly expressed in the
      synovial membrane and articular cartilage, but HAS3 is not.

PMID- 11470162
TI  - The human HMGB1 promoter is modulated by a silencer and an enhancer-containing
      intron.
AB  - The highly conserved, ubiquitous high mobility group protein HMGB1 (formerly
      named as HMG1) is an architectural transcription factor encoded by a single
      functional gene in human. HMGB1 is expressed in almost all cell or tissue types
      studied. In general, it is expressed at a basal level in most cells but at a
      slightly elevated level of 2--3-fold in actively proliferating tissues or
      estrogen stimulated breast cancer cells. To understand the regulatory mechanism
      controlling expression of the human HMGB1 gene, we cloned and analyzed the
      upstream region as well as the first intron of this gene. We found that
      transcription of the human HMGB1 gene in the breast cancer MCF-7 cells starts at
      one major site 57 nucleotides upstream from the first exon-intron boundary.
      Expression of the human HMGB1 gene is under the control of a very strong TATA
      less promoter, which has an activity more than 18-fold that of the SV40 promoter.
      Immediately upstream, a silencer element is present. This silencer can repress
      the activity of the HMGB1 promoter down to just one-sixth. The first intron of
      the human HMGB1 gene contains enhancer elements, which can increase the human
      HMGB1 promoter activity by 2--3-fold. We postulate that the human HMGB1 gene is
      capable of being expressed at a very high level. The basal level of expression
      observed in most cells is probably a result of the strong promoter being held in
      check by the silencer. The 2--3-fold increase in HMGB1 expression observed in
      proliferating cells or breast cancer cells stimulated by estrogen may probably
      result from the action of the enhancer elements in intron 1.

PMID- 11470163
TI  - Cloning and functional characterization of the human heterogeneous nuclear
      ribonucleoprotein type I promoter.
AB  - We have cloned and functionally characterized a portion of the human hnRNP I
      (heterogeneous nuclear ribonucleoprotein type I) gene containing the promoter
      elements. HnRNP I is an alternative splicing modulator of tissue-specific
      transcripts that is expressed in three different isoforms. The DNA sequence at
      the transcription start site, identified by 5'-rapid amplification of cDNA ends,
      shows a high 'GC' content, lacks canonical TATA sequences and contains multiple
      putative Sp1 and NF1 transcription factor-binding sites, a GATA box and a CAAT
      box. By means of a chloramphenicol acetyltransferase reporter construct and
      deletion analyses, we have identified two regions between -770 bp and -206 bp
      that had a positive effect on expression activity in HeLa cells.

PMID- 11470164
TI  - Molecular cloning and characterization of a novel SH3 protein (SLY)
      preferentially expressed in lymphoid cells.
AB  - A novel full-length cDNA was isolated from a murine T-cell lymphoma library that
      has an open reading frame encoding 381 amino acids. The predicted protein (termed
      SLY) contains a Src homology 3 domain and a sterile alpha motif, suggesting that
      it functions as a signaling adaptor protein in lymphocytes. Northern blot and in
      situ hybridization analysis showed a preferential expression in lymphoid tissues.
      The sly gene is located on the X-chromosome in close proximity to genes involved
      in various immune disorders. This is consistent with an additional role of SLY in
      immune pathology.

PMID- 11470165
TI  - An Alu cassette in the human epithelial sodium channel.
AB  - Here, we report the presence of two splice variants of the human epithelial
      sodium channel alpha subunit (h alpha ENaC) containing Alu cassette, namely h
      alpha ENaC+22 and h alpha ENaC+Alu, in various tissues. Functional expression of
      these splice variants with hENaC beta and gamma subunits produced loss-of-channel
      activity in the Xenopus oocyte expression system. Interestingly, coexpression of
      h alpha ENaC+22 or h alpha ENaC+Alu, respectively, with wild type hENaC alpha,
      beta, and gamma subunits enhanced the expression of amiloride-sensitive current
      in oocytes. The presence of Alu sequences in the 3'-untranslated region of h
      gamma ENaC was also identified.

PMID- 11470166
TI  - Identification of the myb-inducible promoter of the chicken Pdcd4 gene.
AB  - The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which
      disrupts the myelomonocytic differentiation program and transforms myelomonocytic
      cells in vivo and in vitro. It is thought that v-Myb exerts its biological
      effects by deregulating the expression of specific target genes, most of which
      are still unknown. c-myb, the cellular progenitor of v-myb, is expressed in all
      immature hematopoietic cells and is presumed to regulate the expression of genes
      that are essential for the development of the hematopoietic system. Recently, we
      have identified the chicken Pdcd4 gene as a novel v-myb target gene. Pdcd4 has
      originally been identified in a screen for genes upregulated in apoptotic cells
      and, more recently, has been implicated in tumor progression. As a myb-regulated
      gene Pdcd4 is of interest because unlike most other myb target genes it is
      expressed in a broad spectrum of hematopoietic cells. As a first step to study
      the regulation of Pdcd4 expression in more detail, we here report the
      identification and preliminary characterization of the myb-inducible promoter of
      the Pdcd4 gene.

PMID- 11470177
TI  - Effect of gamma-irradiation on serum samples on the diagnostic performance of
      ELISA methods for the detection of trypanosomal antibodies.
AB  - The study investigated the effect of gamma-irradiation on bovine serum samples on
      the ability of enzyme-linked immunosorbent assay (ELISA) methods to detect
      trypanosomal antibodies. The serum samples were analysed using two standardised
      indirect ELISA systems. Higher measurement values were observed for most gamma
      irradiated antibody positive and negative test samples. Using cut-off points,
      determined from the analysis of a non-irradiated trypanosomal antibody-negative
      population, the gamma-irradiated sera data showed that there was an increased
      risk of misclassifying samples as false positive or cross-reactive due to
      increased analytical sensitivity and decreased analytical specificity. The
      intraplate precision and agreement between tested and expected values of
      measurements were not altered throughout. The impact on the assays' diagnostic
      performance was estimated by analysing diagnostic sensitivity, diagnostic
      specificity and related parameters. The data demonstrated that although there was
      a bias of higher measurement values after gamma-irradiation, this could be
      compensated after readjustment of the cut-off points to obtain best separation of
      antibody-positive and -negative samples. Thus, for each assay, no significant
      difference of the diagnostic proficiency was found before and after gamma
      irradiation. The practical implications are discussed of a serum sterilisation
      procedure using (60)Co gamma-rays for routine sample testing, assay validation
      and trypanosomosis monitoring and tsetse-fly control and eradication programmes.

PMID- 11470178
TI  - Nested PCR for diagnosis of canine leishmaniosis in peripheral blood, lymph node
      and bone marrow aspirates.
AB  - A nested polymerase chain reaction (PCR) assay was developed using primers
      selected from the genomic DNA of Leishmania infantum and applied to the diagnosis
      of leishmaniosis in peripheral blood in dogs. Blood of 39 dogs of different
      breeds, all sampled in Catalonia (Spain), were tested for leishmaniosis by enzyme
      linked immunosorbent assay (ELISA), western blotting (WB) and peripheral blood
      mononuclear cell (PBMC) culture and nested PCR. Twenty negative controls (healthy
      dogs less than 1-year-old that had not been exposed to a sandfly season) were
      also studied. Nineteen of the 39 dogs studied were positive by ELISA and/or WB,
      and 18 of these had a positive PBMC nested PCR. PBMC nested PCR was negative in
      all the remaining animals that were negative by serological examination,
      including the 20 negative controls. Parasitological examination and nested PCR of
      bone marrow and lymph node aspirate from the 19 dogs positive by serological
      examination, were also positive. These results indicate that PBMC nested PCR is a
      sensitive and specific tool to diagnose leishmaniosis in dogs. The use of PBMC
      has the advantage over bone marrow and lymph node aspirates in that it is a less
      invasive sample.

PMID- 11470179
TI  - A field survey on the status of internal parasites in calves on organic dairy
      farms in southwestern Sweden.
AB  - Infections with internal parasites are one of the most important causes of
      reduced productivity in first-grazing season cattle (FGSC). In conventional
      herds, nematode infections can be controlled by prophylactic anthelmintic
      treatments, but this is prohibited in organic production. The purpose of this
      investigation was to monitor the status of internal parasitism on 15 organic
      cattle enterprises in southwestern Sweden during the 1997 and 1998 grazing
      seasons, and to estimate the benefits of some management practices in parasite
      control. On each farm, the numbers of Eimeria alabamensis oocysts per gram of
      (opg) faeces were counted in seven fresh dung pats collected from the paddock 8
      10 days after the turnout of FGSC. Faecal samples from 5 to 15 FGSC were also
      analysed for nematode eggs per gram (epg) faeces at four occasions during each
      grazing season. In addition, the FGSC and one group of second-grazing season
      cattle (SGSC) were weighed at turnout and housing and at the same time blood
      samples were collected, and analysed for serum pepsinogen concentration and
      antibodies against the lungworm, Dictyocaulus viviparus. On seven farms, 1-6
      samples with more than 100000 opg were found, indicating considerable pasture
      contamination by E. alabamensis. However, clinical signs of coccidiosis were not
      observed. The highest outputs of nematode eggs were observed 45-55 days after
      turnout. More than 500 epg were only observed in 12 (2.2%) of the calves in 1997
      and in three (0.6%) animals in 1998. Only 1% of the serum samples had pepsinogen
      values exceeding 3.6 U tyrosine, indicative of subclinical Ostertagia ostertagi
      infection. Lungworm infection was detected in five and nine herds in 1997 and
      1998, respectively. The number of seropositive animals on these farms ranged
      between one (10%) and seven (70%). Clinical signs of dictyocaulosis were observed
      on two farms. The results indicate that dictyocaulosis is a problem in organic
      dairy herds in Sweden. On the other hand, the study shows that good management
      such as usage of parasite safe pastures and supplementary feeding may help
      control gastrointestinal parasites.

PMID- 11470180
TI  - The influence of stocking rate on transmission of helminth parasites in pigs on
      permanent pasture during two consecutive summers.
AB  - This study was made to elucidate the transmission of nematode infections in
      outdoor pigs at different stocking rates during two consecutive seasons. Five
      pigs (Group 1A) inoculated with low doses of Oesophagostomum dentatum, Ascaris
      suum, and Trichuris suis and five helminth-naive pigs (Group 1B) were turned out
      together in June 1996 on each of four pastures at stocking rates of 100, 240 (two
      pastures) and 576m(2) per pig, respectively. The pigs were slaughtered in early
      October, and pasture infectivity was subsequently measured using helminth-naive
      tracer pigs (Tracer). In 1997, 10 helminth-naive pigs were turned out on each
      pasture in May (Group 2) and again in August (Group 3), and allowed to graze for
      12 weeks. The percentage of grass cover was reduced considerably at the high
      stocking rate in comparison to the other stocking rates. Transmission of all
      three helminths was observed on all pastures. In 1996, the O. dentatum faecal egg
      counts and worm burdens were significantly higher in pigs at the high stocking
      rate compared to pigs at the other stocking rates. O. dentatum did not survive
      the winter and pigs of Group 2 were inoculated with 3000 larvae each to
      reintroduce this parasite. Ascaris suum ELISA values and worm counts were highest
      at the high stocking rate in 1997 (Group 3). Transmission of T. suis was not
      significantly influenced by stocking rate. The results indicate that transmission
      of O. dentatum, and to some extent A. suum is influenced by stocking rate.
      However, both A. suum and T. suis eggs are still expected to constitute a high
      risk of infection on intensively used pastures where eggs may accumulate for
      years. The relationship between host density and helminth transmission seems more
      complex for grazing/rooting pigs than for grazing ruminants. This may be due to
      the differences in behaviour of the animals and the resulting differences in
      microclimate of the developing eggs/larvae.

PMID- 11470181
TI  - Detection of antibodies to Hypoderma lineatum in cattle by Western blotting with
      recombinant hypodermin C antigen.
AB  - The cDNA encoding the entire mature hypodermin C (HC) of Hypoderma lineatum was
      cloned and expressed in Escherichia coli as a glutathione S-transferase fusion
      protein using pGEX vector. The recombinant HC protein (rHC) was tested by Western
      blotting to detect antibodies to H. lineatum in cattle. Western blotting with rHC
      as antigen clearly differentiated between H. lineatum-infested cattle sera and
      normal cattle sera. Forty-six out of forty-eight serum samples from cattle in
      Central Mongolia were positive, whereas all 30 serum samples from cows in
      Hokkaido, Japan, were negative by Western blotting. The result of Western
      blotting was identical to that of a previously developed enzyme-linked
      immunosorbent assay. These data demonstrated that Western blotting, with rHC
      expressed in E. coli, might be a useful method for the diagnosis of cattle
      hypodermosis.

PMID- 11470182
TI  - A comparison of the development and survival of the dung beetle, Onthophagus
      taurus (Schreb.) when fed on the faeces of cattle treated with pour-on
      formulations of eprinomectin or moxidectin.
AB  - Faeces voided by 1-year old cattle at 3-70 days after treatment with a pour-on
      formulation of moxidectin had no detectable effects on development or survival of
      the common dung beetle Onthophagus taurus. In contrast, faeces voided by cattle
      treated with a pour-on formulation of eprinomectin were associated with high
      juvenile mortality during the first 1-2 weeks after treatment. Increased
      mortality also occurred among newly emerged beetles fed on faeces collected 3
      days after eprinomectin treatment and there was evidence of suppressed brood
      production among those that survived. This effect was still apparent even after
      insects fed for a further 10 days on the faeces of untreated cattle. A model
      simulating the effects of drug residues on dung beetle populations suggests that
      in the absence of immigration a single treatment of eprinomectin is capable of
      reducing beetle activity in the next generation by 25-35%. Effects are likely to
      be greatest when treatment coincides with emergence of a new generation of
      beetles.

PMID- 11470183
TI  - Between sound and perception: reviewing the search for a neural code.
AB  - This review investigates the roles of representation, transformation and coding
      as part of a hierarchical process between sound and perception. This is followed
      by a survey of how speech sounds and elements thereof are represented in the
      activity patterns along the auditory pathway. Then the evidence for a place
      representation of texture features of sound, comprising frequency, periodicity
      pitch, harmonicity in vowels, and direction and speed of frequency modulation,
      and for a temporal and synchrony representation of sound contours, comprising
      onsets, offsets, voice onset time, and low rate amplitude modulation, in auditory
      cortex is reviewed. Contours mark changes and transitions in sound and auditory
      cortex appears particularly sensitive to these dynamic aspects of sound. Texture
      determines which neurons, both cortical and subcortical, are activated by the
      sound whereas the contours modulate the activity of those neurons. Because
      contours are temporally represented in the majority of neurons activated by the
      texture aspects of sound, each of these neurons is part of an ensemble formed by
      the combination of contour and texture sensitivity. A multiplexed coding of
      complex sound is proposed whereby the contours set up widespread synchrony across
      those neurons in all auditory cortical areas that are activated by the texture of
      sound.

PMID- 11470184
TI  - Morphological and functional characteristics of cells cultured from the
      endolymphatic sac.
AB  - The endolymphatic sac is a part of the homeostasis-regulating system of the
      membranous labyrinth of the inner ear. Disturbances in the function of the
      endolymphatic sac are believed to be involved in the genesis of different inner
      ear disorders, such as endolymphatic hydrops and Meniere's disease. To make
      studies of the ion- and fluid-regulating mechanisms of the sac possible, a method
      to culture the tissue in vitro was developed. Epithelial cells and fibroblasts
      were morphologically characterised in the cell cultures with light and electron
      microscopy as well as immunohistochemically using antibodies against cytokeratin
      and vimentin. Since mesenchymal cells have been shown to express vimentin and
      epithelial cells cytokeratin, the antibodies against these two intermediate
      filament proteins were used to further confirm the morphological identification.
      In addition, some functional characteristics of the cultured cells from the
      endolymphatic sac were studied. ATP and K(+) were added to the cell cultures and
      changes in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) were determined
      with the fura-2 method. A rapid and transient increase in [Ca(2+)](i) could be
      seen in both epithelial cells and fibroblasts after applying ATP (200 microM)
      extracellularly. However, when K(+) was added in concentrations of 50 mM and 100
      mM, no changes in [Ca(2+)](i) could be seen in either the epithelial cells or the
      fibroblasts. The results show that the cultured endolymphatic sac cells preserve
      their morphological characteristics and maintain a high viability. Accordingly,
      this method provides a tool for further studies of ion transport mechanisms and
      fluid homeostasis in the endolymphatic sac.

PMID- 11470185
TI  - Auditory evoked responses in control subjects and in patients with problem
      tinnitus.
AB  - Auditory brainstem responses (ABRs) and middle latency responses (MLRs) recorded
      from problem-tinnitus patients were compared with responses from normal hearing,
      hearing loss, and elderly subjects. Ten stimulus frequencies were presented in
      counterbalanced sequence and all frequencies were presented before any given
      frequency was presented again. The variables of importance were problem-tinnitus,
      hearing loss, subject age and stimulus frequency. Repeated measures analysis of
      variance showed a significant difference only in the latency of ABR wave 7. The
      intrinsically high variability in the problem-tinnitus and elderly groups
      rendered standard statistical analyses ineffective with the sample sizes used.
      Alternative analyses were employed in which the MLR waves of the normal hearing
      subjects were taken as the standard against which the other groups were compared.
      Very large MLR waves occurred in some, but not all, of the subjects in the
      problem-tinnitus and elderly groups. Different MLR waves were large in different
      subjects without correspondingly large ABR potentials. These results suggest: (1)
      selective alteration of MLR generators in different forms of tinnitus; and (2)
      differing effects of age on auditory physiology. Stimulus frequency and hearing
      loss contributed to this multivariate picture. Another variable, the average
      sound pressure level of the long-term acoustic environment, may also be
      important.

PMID- 11470186
TI  - Proteoglycan arrays in the cochlear basement membrane.
AB  - Indirect immunofluorescence and transmission electron microscopy were used to
      investigate the composition and assembly of proteoglycans in the basement
      membranes of the spiral limbus, basilar membrane, spiral ligament, Reissner's
      membrane, myelinated nerve fibers, and blood capillaries of the spiral ligament
      and stria vascularis in the chinchilla cochlea. Four types of basement membrane
      components: laminin, entactin/nidogen, type IV collagen and heparan sulfate
      proteoglycans were immunolocalized in all basement membranes in association with
      heparan sulfate proteoglycans. beta 1 and alpha 1 integrin subunits were also
      detected along these basement membranes. The concentration of the basement
      membrane-associated proteins and integrin subunits differed according to the
      adjacent cell type. Electron microscopy showed that all basement membranes, with
      exception of those of stria vascularis, consist of two layers: lamina lucida and
      lamina densa. In the stria vascularis only a homogeneous lamina densa was
      observed. Cuprolinic blue treatment revealed heterogeneity in the ultrastructure
      and arrangement of proteoglycans in the cochlear basement membranes.
      Proteoglycans of the subepithelial basement membrane in the spiral limbus and
      spiral ligament formed quasi-regular, linear arrays within the lamina lucida, or
      were located at both sides of the lamina densa in the basilar membrane and
      Reissner's membrane. In the basement membranes of nerve fibers, and capillaries
      in the spiral ligament and stria vascularis, proteoglycans were scattered
      throughout these basement membranes, but showed different concentration and
      ultrastructural appearance, which may be related to different filtration and
      mechanical properties. In the basilar membrane, PGs were located above and below
      the lamina densa. An additional layer of PGs below the lamina densa may function
      as increased mechanical support of organ of Corti by its interaction with
      underlying fibrillar collagen layer. In the stria vascularis capillaries, PGs
      were stained considerably less with Cuprolinic blue and were scattered through
      the lamina densa of the basement membrane compared to capillaries of spiral
      ligament. This observation is compatible with a higher permeability of the strial
      capillaries.

PMID- 11470187
TI  - Selective aspects of human pathology in high-tone hearing loss of the aging inner
      ear.
AB  - Accompanied with aging, the thresholds for high frequency sounds may elevate and
      result in a progressive hearing loss described as presbycusis. Based on
      correlations between audiometric measures of aged patients and histologic
      findings garnered from postmortem examinations, four types of presbycusis have
      been characterized: sensory-neural, neural, strial, and conductive [Schuknecht,
      H.F., Gacek, M.R., 1993. Ann. Otol. Rhinol. Laryngol. 102, 1--16]. Otopathologic
      changes to the inner ear as a direct function of age, however, remain
      controversial. The focus of this investigation involves the pathological impact
      on remaining sensory structures in patients having sensory--neural degeneration.
      The current study presents seven human temporal bones extracted from patients
      aged 53--67 years with high-tone hearing loss and with no known history of
      extraordinary environmental events involving head or noise trauma, acoustic
      overstimulation, or ototoxicity. In previously published findings of these
      specimens, all but one temporal bone failed to demonstrate a meaningful
      correlation between audiometric measurements and loss of functional hair cell
      populations with secondary retrograde degeneration of nerve fibers. Using the
      block surface method, electron microscopic micrographs demonstrate
      ultrastructural changes in the cuticular plate, stereocilia, pillar cells, stria
      vascularis, and the spiral ligament. In all pathological specimens, the greatest
      incidence of degeneration was seen at the cuticular plate. Conclusively, our
      findings present three implications in the aging human cochlea: firstly,
      audiometric measures that represent a high-tone hearing loss may take various
      forms with respect to ultrastructural patterns of degeneration and surviving
      structures; secondly, the incidence of lipofuscin and lysosome granules does not
      correlate with the degree of hearing loss and; thirdly, as shown only in guinea
      pigs [Anniko, M., 1988. Scanning Microsc. 2, 1035--1041], high-tone hearing loss
      can be associated with deformation of the cuticular plate.

PMID- 11470188
TI  - Estrogen receptors in the normal adult and developing human inner ear and in
      Turner's syndrome.
AB  - The influence of estrogens, the female sex hormone, on the ear and hearing is yet
      not fully investigated, though some studies have suggested that estrogens may
      influence hearing functions. The presence of estrogen receptors alpha and beta
      has earlier been shown in the inner ear of mice and rats. The aim of this study
      was to map possible estrogen receptors in the human inner ear. Inner ear tissue
      from human adults, aborted human normal fetuses and fetuses with Turner's
      syndrome were collected. Paraffin embedded sections of adult and fetal inner ears
      were immunostained with antibodies against estrogen receptors alpha and beta.
      Estrogen receptor alpha containing cells were found in the adult human inner ear
      only in the spiral ganglion, and estrogen receptor beta in the stria vascularis
      solely. The human fetal inner ear tissue from both normal and Turner fetuses
      showed a very weak staining of estrogen receptor alpha in the spiral ganglion
      cells, but no specific labeling of the Kolliker's organ of Corti at 13, 14 and 18
      weeks of age. No staining of estrogen receptor beta was seen in the fetal inner
      ear.

PMID- 11470189
TI  - Mitochondrial cytochrome oxidase immunolabeling in aged human temporal bones.
AB  - Presbycusis, an age-related hearing loss, is accompanied by histopathological
      cochlear changes including variable amounts of degeneration of the auditory
      receptors, neurons and the stria vascularis. The causes of degeneration are
      unknown, although acoustic trauma and exposure to ototoxic agents are certainly
      contributors to the cellular degeneration. Acquired mitochondrial DNA defects are
      postulated as important determinants of aging in neuromuscular tissues. The
      cochlear neurons are highly metabolic and are, therefore, likely to be affected
      by mitochondrial DNA defects. Sequence analysis has demonstrated a significant
      number of acquired mutations in the cytochrome oxidase gene in the neurons from
      aged human cochleas. The current study used immunohistochemical labeling of
      cytochrome oxidase in the neuronal cell bodies in archival celloidin sections to
      evaluate relationships among label density, hearing loss, number of neurons and
      mitochondrial DNA changes within individual cochleas. Label density was less in
      many aged temporal bones, but not all. There was no relationship among any other
      variables. It is concluded that while there may be a decrease in the amount of
      cytochrome oxidase expression in aged spiral ganglion cell bodies, there are many
      other factors that contribute to hearing loss and cellular degeneration.

PMID- 11470190
TI  - OCP1, an F-box protein, co-localizes with OCP2/SKP1 in the cochlear epithelial
      gap junction region.
AB  - Immunohistochemical data indicate that OCP1 co-localizes exactly with OCP2 in the
      epithelial gap junction region of the guinea pig organ of Corti (OC). Despite the
      abundance of OCP1 in the OC, gaining access to its coding sequence -- and, in
      particular, the 5' end of the coding sequence -- proved unexpectedly challenging.
      The putative full-length OCP1 cDNA -- 1180 nucleotides in length -- includes a 67
      nucleotide 5' leader sequence, 300 codons (including initiation and termination
      signals), and a 216 nucleotide 3' untranslated region. The cDNA encodes a protein
      having a predicted molecular weight of 33,700. The inferred amino acid sequence
      harbors an F-box motif spanning residues 52--91, consistent with a role for OCP1
      and OCP2 in the proteasome-mediated degradation of select OC proteins. Although
      OCP1 displays extensive homology to an F-box protein recently cloned from rat
      brain (NFB42), clustered sequence non-identities indicate that the two proteins
      are transcribed from distinct genes. The presumptive human OCP1 gene was
      identified in the human genome databank. Located on chromosome 1p35, the inferred
      translation product exhibits 94% identity with the guinea pig OCP1 coding
      sequence.

PMID- 11470191
TI  - Functional development of the inferior colliculus (IC) and its relationship with
      the auditory brainstem response (ABR) in the tammar wallaby (Macropus eugenii).
AB  - To discover the developmental relationship between the auditory brainstem
      response (ABR) and the focal inferior colliculus (IC) response, 32 young tammar
      wallabies were used, by the application of simultaneous ABR and focal brainstem
      recordings, in response to acoustic clicks and tone bursts of seven frequencies.
      The IC of the tammar wallaby undergoes a rapid functional development from
      postnatal day (PND) 114 to 160. The earliest (PND 114) auditory evoked response
      was recorded from the rostral IC. With development, more caudal parts of the IC
      became functional until age about PND 127, when all parts of the IC were
      responsive to sound. Along a dorsoventral direction, the duration of the IC
      response decreased, the peak latency shortened, while the amplitude increased,
      reaching a maximum value at the central IC, then decreased. After PND 160, the
      best frequency (BF) of the ventral IC was the highest, with values between 12.5
      and 16 kHz, the BF of the dorsal IC was the lowest, varying between 3.2 and 6.4
      kHz, while the BF of the central IC was between 6.4 and 12.5 kHz. Between PND 114
      and 125, the IC response did not have temporal correlation with the ABR. Between
      PND 140 and 160, only the early components of the responses from the ventral and
      central IC correlated with the P4 waves of the ABR. After PND 160, responses
      recorded from different depths of the IC had a temporal correlation with the ABR.

PMID- 11470192
TI  - Effect of middle ear components on eardrum quasi-static deformation.
AB  - Eardrum deformation induced by quasi-static middle ear pressure was studied at
      progressive stages of dissection of gerbil temporal bones. With our high
      resolution moire interferometer we recorded the shape and deformation of the
      eardrum along a line perpendicular to the manubrium and through the umbo, at
      different middle ear pressures. The deformation was measured from the medial
      side, after serially removing the cochlea, removing the stapes, cutting the
      tensor tympani, exposing the incudo-mallear joint, and cutting the anterior bony
      process which connects the malleus to the tympanic bone. The mean displacement as
      a function of pressure was also determined at all stages of dissection. Removing
      the cochlea and stapes, and cutting tensor tympani has no effect on static
      eardrum deformation. Exposing the incudo-mallear joint increases eardrum
      movement, and cutting the anterior bony connection between malleus and temporal
      bone strongly changes eardrum rest position and further increases its
      displacement.

PMID- 11470193
TI  - Audiograms of five species of rodents: implications for the evolution of hearing
      and the perception of pitch.
AB  - Behavioral audiograms were determined for five species of rodents: groundhog
      (Marmota monax), chipmunk (Tamias striatus), Darwin's leaf-eared mouse (Phyllotis
      darwinii), golden hamster (Mesocricetus auratus), and Egyptian spiny mouse
      (Acomys cahirinus). The high-frequency hearing of these animals was found to vary
      inversely with interaural distance, a typical mammalian pattern. With regard to
      low-frequency hearing, the animals fell into two groups: those with extended low
      frequency hearing (chipmunks, groundhogs, and hamsters hear below 100 Hz) and
      those with restricted low-frequency hearing (spiny and leaf-eared mice do not
      hear appreciably below 1 kHz). An analysis of mammalian hearing reveals that the
      distribution of low-frequency hearing limits is bimodal with the two
      distributions separated by a gap from 125 to 500 Hz. The correspondence of this
      dichotomy with studies of temporal coding raises the possibility that mammals
      that do not hear below 500 Hz do not use temporal encoding for the perception of
      pitch.

PMID- 11470194
TI  - Quantitative determination of piroxicam in a new formulation (piroxicam-beta
      cyclodextrin) by derivative UV spectrophotometric method and HPLC.
AB  - A derivative ultraviolet (UV) spectrophotometric method for the determination of
      piroxicam in piroxicam--beta-cyclodextrin tablets was developed. Phosphate buffer
      (pH 7.8, 0.1 M) and ethanol were used as a solvent system throughout the study.
      In this study, determination of piroxicam was conducted by using first order
      derivative amplitudes at 261.4 nm (n=4). Standards for the calibration graph
      ranging from 2.40 to 20.0 microg/ml were prepared from working standard. The
      proposed method is accurate with 99.70%+/-0.50 recovery value and precise with
      coefficient of variation (CV) of 1.29. The results were compared with those
      obtained using a high-performance liquid chromatography (HPLC) procedure. A
      reversed-phase C(18) column with aqueous phosphate buffer:methanol, 60:40, v/v,
      mobile phase was used. UV detector was set at 254 nm. Calibration solutions used
      in HPLC were ranging from 5 to 20 microg/ml. Results obtained in HPLC were
      comparable to those obtained by derivative UV spectrophotometric method.

PMID- 11470195
TI  - LC determination of morphine and morphine glucuronides in human plasma by
      coulometric and UV detection.
AB  - A reversed-phase high-performance liquid chromatographic method with coulometric
      and UV detection has been developed for the simultaneous determination of
      morphine, morphine-3-glucuronide and morphine-6-glucuronide. The separation was
      carried out by using a Supelcosil LC-8 DB reversed-phase column and 0.1 M
      potassium dihydrogen phosphate (pH 2.5)--acetonitrile--methanol (94:5:1 v/v)
      containing 4 mM pentanesulfonic acid as the mobile phase. The compounds were
      determined simultaneously by coulometry for morphine and with UV detection for
      morphine-3-glucuronide and morphine-6-glucuronide. Morphine, morphine
      glucuronides and the internal standard were extracted from human plasma using
      Bond-Elut C18 (1 ml) solid-phase extraction cartridges. In the case of
      coulometric detection, the detection limit was 0.5 ng/ml for morphine; in the
      case of UV detection the detection limit was 10 ng/ml for morphine-3-glucuronide
      and for morphine-6-glucuronide, too.

PMID- 11470196
TI  - Speciation of low molecular weight Al complexes in serum of CAPD patients.
AB  - Speciation of LMW--Al complexes was performed in human serum of six continuous
      ambulatory peritoneal dialysis (CAPD) patients in order to investigate the
      individual variability in the percentage and the composition of LMW--Al species.
      The total concentration of Al in serum ranged from 10 to 120 ng ml(-1). The
      samples with high total concentration of Al were analysed directly, while those
      of low total Al concentration were spiked with Al(3+). Spiked and non-spiked
      samples (100--120 ng ml(-1) of total Al) were microultrafiltered through a
      membrane filter (cut-off 30,000 Da) to separate Al-transferrin from LMW-Al
      complexes. On an anion-exchange fast protein liquid chromatography (FPLC) column,
      0.2 ml of filtrate was injected. An aqueous -- 4 mol l(-1) NH(4)NO(3) linear
      gradient elution was applied for 10 min to separate LMW--Al complexes. Fractions
      of 0.2 ml collected throughout the chromatographic run were diluted 1:1 with
      water and Al determined 'off line' by electrothermal atomic absorption
      spectrometry (ETAAS). The characterisation of LMW-Al species eluted under the
      chromatographic peaks was performed also by electrospray tandem mass
      spectrometric (ES-MS-MS) analysis. It was found experimentally that the
      percentage of LMW--Al species in spiked and non-spiked serum ranged from 25 to
      50% (in one non-spiked sample 100%). The following LMW--Al species were separated
      and identified during the chromatographic run: Al-phosphate and a mixture of Al
      citrate and ternary Al-citrate--phosphate complexes. It was found experimentally
      that the distribution of these species varied among particular patients. Similar
      distribution of LMW--Al species was found in spiked serum of healthy volunteers.

PMID- 11470197
TI  - Spectrophotometric determination of trifluoperazine HCl and isopropamide iodide
      in binary mixture using second derivative and second derivative of the ratio
      spectra methods.
AB  - Two methods are presented for the simultaneous determination of trifluoperazine
      hydrochloride and isopropamide iodide in binary mixture. The first method depends
      on second derivative ((2)D) ultraviolet spectrophotometry, with zero crossing and
      peak to base measurement. The second derivative amplitudes at 270.4 and 230.2 nm
      were selected for the assay of trifluoperazine hydrochloride and isopropamide
      iodide, respectively. The second method depends on second derivative of the ratio
      spectra by division of the absorption spectrum of the binary mixture by a
      normalized spectrum of one of the components and then calculating the second
      derivative of the ratio spectrum. The second derivative of the ratio amplitudes
      at 257 and 228 nm were selected for the determination of trifluoperazine
      hydrochloride and isopropamide iodide, respectively. The two proposed methods
      were successfully applied to the determination of the two drugs in laboratory
      prepared mixtures and in commercial tablets.

PMID- 11470198
TI  - Spectrophotometric, spectrofluorimetric and LC determination of trazodone
      hydrochloride.
AB  - Three methods are described for the determination of trazodone hydrochloride in
      pharmaceutical tablets. The spectrophotometric method was based on the formation
      of yellow ion pair complex between the basic nitrogen of the drug and bromophenol
      blue at pH 3.4. The formed complex was extracted with chloroform and measured at
      414 nm. The spectrofluorimetric method was based on measurement of the native
      fluorescence of the drug in 50% acetic acid upon excitation at a maximum of 320
      nm and the emission wavelength is 435 nm. The third method was based on the high
      performance liquid chromatographic determination of trazodone hydrochloride using
      a reversed phase, ODS column, with a mobile phase of acetonitrile--phosphate
      buffer at pH 4.5 (60:40, v/v). Quantization was achieved with UV detection at 250
      nm based on peak area. The three methods were simple, accurate and suitable for
      quality control application.

PMID- 11470199
TI  - Molecular recognition in a reconstituted tumor cell membrane.
AB  - The design of an immunoliposome system for molecular recognition using
      reconstituted, hydrogel-supported bilayer lipid membranes (sb-BLMs) is described.
      By monitoring the electrical properties, two kinds of recognition are feasible:
      (i) the human bladder tumor cells, Ej and its antibody BDI-1, the lifetime of the
      reconstituted membrane is 42 min; and (ii) the human rectum tumor cells, LOVO,
      the life of the reconstructed membrane is more than 40 min, the same as
      conventional BLM. Further, the anticancer drug, Adriamycin (Anticancer Res., 20
      (2000) 1391), was shown to be effective in such reconstituted systems, the life
      of which is less than 5 min. In these experiments, the active ingredients of the
      Ej and LOVO cells were determined on reconstituted sb-BLMs. The key point is that
      the component part being recognized on the BLM must be kept in its native state.

PMID- 11470200
TI  - Combining spectroscopic data (MS, IR): exploratory chemometric analysis for
      characterising similarity/diversity of chemical structures.
AB  - Combined infrared--mass spectra (IR--MS) have been used to examine a small data
      set of synthetic substances in order to elucidate whether a combination of
      spectral descriptors yield better classification and similarity predictions than
      their corresponding individual spectral descriptors. To eliminate differences in
      variation, a logarithmic transformation or log double-centering pretreatment was
      necessary. Principal component analysis (PCA) was applied to observe clusters of
      similar compounds. Hierarchical upgma-cluster analysis was also used for data
      classification.

PMID- 11470201
TI  - ANN modeling of the penetration across a polydimethylsiloxane membrane from
      theoretically derived molecular descriptors.
AB  - A quantitative structure-permeability relationship was developed using Artificial
      Neural Network (ANN) modeling to study penetration across a polydimethylsiloxane
      membrane. A set of 254 compounds and their experimentally derived maximum steady
      state flux values used in this study was gathered from the literature. A total of
      42 molecular descriptors were calculated for each compound. A genetic algorithm
      was used to select important molecular descriptors and supervised ANN was used to
      correlate selected descriptors with the experimentally derived maximum steady
      state flux through the polydimethylsiloxane membrane (log J). Calculated
      molecular descriptors were used as the ANN's inputs and log J as the output.
      Developed model indicates that molecular shape and size, inter-molecular
      interactions, hydrogen-bonding capacity of drugs, and conformational stability
      could be used to predict drug absorption through skin. A 12-descriptor nonlinear
      computational neural network model has been developed for the estimation of log J
      values for a data set of 254 drugs. Described model does not require experimental
      parameters and could potentially provide useful prediction of membrane
      penetration of new drugs and reduce the need for actual compound synthesis and
      flux measurements.

PMID- 11470202
TI  - A Plackett-Burnam screening design directs the efficient formulation of
      multicomponent DRV liposomes.
AB  - A computer-based technique was applied for the optimization of recently described
      multicomponent protective liposomal formulations. These formulations contain
      riboflavin in either free form or complexed with gamma-cyclodextrin as a model
      drug, sensitive to photochemical degradation, as well as various light absorbers
      and antioxidants incorporated into the lipid bilayer and/or the aqueous phase of
      liposomes. During the liposomal preparation, a series of 11 factors were isolated
      as important to affect their effectiveness as stabilization systems. These
      factors were related, first, to the composition of liposomes and, second, to
      variations during the preparation procedure. The Plackett--Burnam design
      described in this study was applied for the isolation of the significant factors
      in order to concentrate more on them. The stabilization ratio of the vitamin was
      the response variable of the system to be optimized. In order to assure the
      presence of the examined components in liposomes, the entrapment values were
      calculated for all the materials, either spectrophotometrically or using second
      order derivative spectrophotometry. The optimum formulation should be
      characterized from the higher protection of the drug.

PMID- 11470203
TI  - Kinetic spectrophotometric methods for the quantitation of triprolidine in bulk
      and in drug formulations.
AB  - A kinetic method for the accurate and sensitive determination of triprolidine has
      been described. The method is based on the alkaline oxidation of triprolidine
      with KMnO(4). At a fixed time of 20 min, the formed manganate ion is
      spectrophotometrically measured at 612 nm. The concentration of triprolidine is
      calculated using the calibration equation for the fixed time method. Beer's law
      was obeyed from 6 to 40 microg ml(-1) and the R.S.D. (n=10) was 0.97%. Recovery
      was 99.80%. The method is suitable for quantitative determination of triprolidine
      in the presence of co-formulated drugs, since pseudoephedrine hydrochloride,
      which is frequently co-formulated with triprolidine did not interfere with this
      assay. The intra- and inter-day R.S.D. values indicated the ruggedness of the
      method. The method has been applied successfully to commercial tablet dosage
      form. The results obtained agreed with those obtained by the BP method. The
      determination of triprolidine by the fixed-concentration and rate constant
      methods is feasible with the calibration equations obtained, but the fixed time
      method proves to be more applicable.

PMID- 11470204
TI  - Spectrophotometric simultaneous determination of triamterene and
      hydrochlorothiazide in triamterene-H tablets by multivariate calibration methods.
AB  - The multivariate calibration methods of partial least-square regression and
      principal component regression were applied for the simultaneous
      spectrophotometry determination of triamterene (TRM) and hydrochlorothiazide
      (HYD) in their mixtures. The parameters of the chemometric procedure were
      optimized, and the proposed methods were validated with synthetic samples and
      applied to analyze these drugs in pharmaceutical products with good accuracy and
      precision. The results were compared with those given by the British
      Pharmacopoeia (BP) method. The square of the correlation coefficients (R(2)) for
      predicted TRM and HYD with the proposed method in a test sample were 0.9994 and
      0.9992, respectively. The relative standard deviation for commercial tablets in
      the proposed method and BP standard method were 0.405 and 2.142%, respectively.

PMID- 11470205
TI  - Determination of depleted uranium, pyridostigmine bromide and its metabolite in
      plasma and urine following combined administration in rats.
AB  - A simple and reliable method was developed for the quantification of depleted
      uranium, the anti nerve agent drug pyridostigmine bromide (PB;3
      dimethylaminocarbonyloxy-N-methyl pyridinium bromide) and its metabolite N-methyl
      3-hydroxypyridinium bromide in rat plasma and urine. The method involved using
      solid phase extraction and spectrophotometric determination of uranium, and high
      performance liquid chromatography (HPLC) with reversed phase C(18) column, and UV
      detection at 280 nm for PB and its metabolite. Uranium was derivatized using
      dibenzoylmethane (DBM) then the absorbance was measured at 405 nm. PB and its
      metabolite were separated using a gradient of 1--40% acetonitrile in 0.1%
      triflouroacetic acid water solution (pH 3.2) at a flow rate of 0.8 ml/min in a
      period of 14 min. Limits of detection were 2 ng/ml for uranium and 50 ng/ml for
      PB and its metabolite. Limits of quantitation were between 10 and 100 ng/ml for
      uranium and the other two analytes, respectively. Average percentage recovery of
      five spiked plasma samples were 83.7+/-8.6, 76.8+/-6.7, 79.1+/-7.1, and from
      urine 82.7+/-8.6, 79.3+/-9.5 and 78.0+/-6.2, for depleted uranium, PB and N
      methyl-3-hydroxypyridinium bromide, respectively. The relationship between peak
      areas and concentration was linear for standards between 100 and 1000 ng/ml for
      all three analytes. This method was applied to analyze the above chemicals and
      metabolites following combined administration in rats.

PMID- 11470206
TI  - Simultaneous determination of malathion, permethrin, DEET (N,N-diethyl-m
      toluamide), and their metabolites in rat plasma and urine using high performance
      liquid chromatography.
AB  - A method was developed for the separation and quantification of the insecticide
      malathion (O,O-dimethyl-S-(1,2-carbethoxyethyl) phosphorodithioate), its
      metabolite malaoxon (O,O-dimethyl-S-(1,2-carbethoxyethyl) phosphorothioate), the
      insecticide permethrin (3-(2,2-dichloro-ethenyl)-2,2
      dimethylcyclopropanecarboxylic acid(3-phenoxyphenyl)methylester), two of its
      metabolites m-phenoxybenzyl alcohol and m-phenoxybenzoic acid, the insect
      repellent N,N-diethyl-m-toluamide (DEET), and its metabolites m-toluamide and m
      toluic acid in rat plasma and urine. The method used high performance liquid
      chromatography (HPLC) with reversed phase C(18) column, and UV detection at 210
      nm. The compounds were separated using gradient of 45--99% acetonitrile in water
      (pH 3.5) at a flow rate ranging between 0.5 and 2 ml/min in a period of 15 min.
      The retention times ranged from 7.4 to 12.3 min. The limits of detection ranged
      between 20 and 100 ng/ml, while limits of quantitation were 50-150 ng/ml. Average
      percentage recovery of five spiked plasma samples were 80.1+/-4.2, 75.2+/-4.6,
      84.5+/-4.0, 84.3+/-3.4, 82.8+/-3.9, 83.9+/-5.5, 82.2+/-6.0, 83.1+/-4.3, and from
      urine 78.8+/-3.9, 76.4+/-4.9, 82.3+/-4.5, 82.5+/-3.9, 81.4+/-4.0, 83.9+/-4.3,
      81.5+/-5.0, and 84.5+/-3.8 for, malathion, malaoxon, DEET, m-toluamide, m-toluic
      acid, permethrin, m-phenoxybenzyl alcohol, and m-phenoxybenzoic acid,
      respectively. The method was reproducible and linear over range between 100 and
      1000 ng/ml. This method was applied to analyze the above chemicals and
      metabolites following combined dermal administration in rats.

PMID- 11470207
TI  - Simultaneous determination of clozapine and its N-desmethyl and N-oxide
      metabolites in plasma by liquid chromatography/electrospray tandem mass
      spectrometry and its application to plasma level monitoring in schizophrenic
      patients.
AB  - A liquid chromatography tandem mass spectrometry (LC-MS-MS) assay method for the
      simultaneous determination of clozapine and its N-desmethyl (norclozapine) and N
      oxide metabolites in human plasma is described. The compounds were extracted from
      plasma by a single step liquid-liquid extraction procedure and analyzed using a
      high performance liquid chromatography electrospray tandem mass spectrometer
      system. The compounds were eluted isocratically on a C-18 column, ionized using
      positive ion atmospheric pressure electrospray ionization method by a
      TurboIonspray source and analyzed using multiple reaction monitoring mode. The
      ion transitions monitored were m/z 327 --> m/z 270 for clozapine, m/z 313 --> m/z
      192 for norclozapine, m/z 343 --> m/z 256 for clozapine-N-oxide and m/z 421-->
      m/z 201 for internal standard. The standard curves of clozapine, norclozapine and
      clozapine-N-oxide were linear over the range of 1 ng/ml to 1000 ng/ml when 0.5 ml
      of plasma was used for the analysis (r(2) >0.998). Three pooled plasma samples
      collected from patients who were treated with clozapine were used as long-term
      quality control samples to check the validity of spiked standard curve samples
      made at various times. The intra- and inter-assay variations for the spiked
      standard curve and quality control samples were less than 14%. These variations
      for the long-term patient quality control samples were less than 11%. The LC-MS
      MS assay for simultaneous determination of clozapine, norclozapine and clozapine
      N-oxide reported here is highly specific, sensitive, accurate and rapid. This
      method is currently being used for the plasma level monitoring of clozapine and
      its N-desmethyl and N-oxide metabolites in patients treated with clozapine. The
      plasma levels of clozapine, norclozapine and clozapine-N-oxide varied widely
      within and among patients. The data revealed that the norclozapine and clozapine
      N-oxide metabolites were present at about 58%+/-14% and 17%+/-6% of clozapine
      concentrations in plasma, respectively.

PMID- 11470208
TI  - High-performance liquid chromatographic analysis of mometasone furoate and its
      degradation products: application to in vitro degradation studies.
AB  - A method of analysis of mometasone furoate in pharmaceutical formulations and
      biological fluids is necessary to study the degradation kinetics and determine
      its stability. A simple high-performance liquid chromatographic method was
      developed for simultaneous determination of mometasone furoate and its
      degradation products in human plasma. Plasma (0.5 ml) was extracted with
      dichloromethane after addition of the internal standard, dexamethasone 21
      acetate. Separation was achieved on a Beckman C(8) column with UV detection at
      248 nm. The calibration curve was linear ranging from 0.2 to 100 microg/ml. The
      mean extraction efficiency was >86%. Precision of the assay was <10% (CV), and
      was within 10% at the limit of quantitation (0.2 microg/ml). Bias of the assay
      was lower than 7%. The limit of detection was 50 ng/ml for a 0.5-ml sample. The
      assay was applied successfully to the in vitro kinetic study of degradation of
      mometasone furoate in human plasma and simulated biological fluids.

PMID- 11470209
TI  - The simultaneous determination of diazepam and its three metabolites in dog
      plasma by high-performance liquid chromatography with mass spectroscopy
      detection.
AB  - A fast, sensitive and specific LC/MS/MS method for the simultaneous determination
      of diazepam and its three metabolites, oxazepam, temazepam and desmethyldiazepam,
      in dog plasma is described. The method consists of an automated 96-well solid
      phase extraction procedure and electrospray LC/MS/MS analysis. D(5)-Diazepam is
      used as the internal standard for all the compounds. Intra-day and inter-day
      assay coefficients of variations are less than 12.7%. The lower limit of
      quantitation (LLOQ) is 1 nM for each analyte, based on 0.1 ml aliquots of dog
      plasma. The analytical run time was 5 min. Linearity is observed over the range
      of 1--500 nM. This method has been used to support the discovery of
      pharmacokinetic studies.

PMID- 11470210
TI  - HPLC determination of phenylpropanolamine in pharmaceutical preparations using 4
      dimethylaminobenzaldehyde as a derivatizing reagent.
AB  - A method is described for the high performance liquid chromatographic (HPLC)
      determination of phenylpropanolamine (PPA) based on precolumn derivatization with
      4-dimethylaminobenzaldehyde (DAB) and elution from phenomenex C-18 column with
      methanol-water and detection by spectrophotometry at 418 nm. Linear calibration
      was obtained with 9.4--46.9 microg ml(-1) with a detection limit of 4.7 ng ml(
      1). Vitamin B(12) and rifampicin when present together with PPA separated
      completely and could be determined simultaneously. PPA was determined in
      pharmaceutical preparations with a relative standard deviation of 0.6--1.6%.

PMID- 11470212
TI  - AIM portraits: tracing the evolution of artificial intelligence in medicine and
      predicting its future in the new millennium.

PMID- 11470213
TI  - AI in medicine on its way from knowledge-intensive to data-intensive systems.
AB  - The last 20 years of research and development in the field of artificial
      intelligence in medicine (AIM) show a path from knowledge-intensive systems,
      which try to capture the essential knowledge of experts in a knowledge-based
      system, to data-intensive systems available today. Nowadays enormous amounts of
      information is accessible electronically. Large datasets are collected
      continuously monitoring physiological parameters of patients. Knowledge-based
      systems are needed to make use of all these data available and to help us to cope
      with the information explosion. In addition, temporal data analysis and
      intelligent information visualization can help us to get a summarized view of the
      change over time of clinical parameters. Integrating AIM modules into the daily
      routine software environment of our care providers gives us a great chance for
      maintaining and improving quality of care.

PMID- 11470214
TI  - Proactive health computing.
AB  - In an analysis departing from the global health situation, the foundation for a
      change of paradigm in health informatics based on socially embedded information
      infrastructures and technologies is identified and discussed. It is shown how an
      increasing computing and data transmitting capacity can be employed for proactive
      health computing. As a foundation for ubiquitous health promotion and prevention
      of disease and injury, proactive health systems use data from multiple sources to
      supply individuals and communities evidence-based information on means to improve
      their state of health and avoid health risks. The systems are characterised by:
      (1) being profusely connected to the world around them, using perceptual
      interfaces, sensors and actuators; (2) responding to external stimuli at faster
      than human speeds; (3) networked feedback loops; and (4) humans remaining in
      control, while being left outside the primary computing loop. The extended
      scientific mission of this new partnership between computer science, electrical
      engineering and social medicine is suggested to be the investigation of how the
      dissemination of information and communication technology on democratic grounds
      can be made even more important for global health than sanitation and urban
      planning became a century ago.

PMID- 11470215
TI  - The socio-organizational age of artificial intelligence in medicine.
AB  - The increasing pressure on Health Care Organizations (HCOs) to ensure efficiency
      and cost-effectiveness, balancing quality of care and cost containment, will
      drive them towards a more effective management of medical knowledge derived from
      research findings. The relation between science and health services has until
      recently been too casual. The primary job of medical research has been to
      understand the mechanisms of disease and produce new treatments, not to worry
      about the effectiveness of the new treatments or their implementation. As a
      result many new treatments have taken years to become part of routine practice,
      ineffective treatments have been widely used, and medicine has been opinion
      rather than evidence based. This results in suboptimal care for patients.
      Knowledge management technology may provide effective approaches in speeding up
      the diffusion of innovative medical procedures whose clinical effectiveness have
      been proved: the most interesting one is represented by computer-based
      utilization of evidence-based clinical guidelines. As researchers in Artificial
      Intelligence in Medicine (AIM), we are committed to foster the strategic
      transition from opinion to evidence-based decision making. Reviews of the
      effectiveness of various methods of guideline dissemination show that the most
      predictable impact is achieved when the guideline is made accessible through
      computer-based and patient specific reminders that are integrated into the
      clinician's workflow. However, the traditional single doctor-patient relationship
      is being replaced by one in which the patient is managed by a team of health care
      professionals, each specializing in one aspect of care. Such shared care depends
      critically on the ability to share patient-specific information and medical
      knowledge easily among them. Strategically there is a need to take a more
      clinical process view of health care delivery and to identify the appropriate
      organizational and information infrastructures to support this process. Thus, the
      great challenge for AIM researchers is to exploit the astonishing capabilities of
      new technologies to disseminate their tools to benefit HCOs by assuring the
      conditions of knowledge management and organizational learning at the fullest
      extent possible. To achieve such a strategic goal, a guideline can be viewed as a
      model of the care process. It must be combined with an organization model of the
      specific HCO to build patient careflow management systems. Artificial
      intelligence can be extensively used to design innovative tools to support all
      the development stages of those systems. However, exploiting the knowledge
      represented in a guideline to build them requires to extend today's workflow
      technology by solving some challenging problems.

PMID- 11470216
TI  - Multiple representations and multi-modal reasoning in medical diagnostic systems.
AB  - The paper examines the motivations for developing medical diagnostic systems
      exploiting multiple representations and multi-modal reasoning. The analysis is
      carried on by revisiting the architectural choices of the CHECK system (developed
      in late 1980s) which combined heuristic and causal knowledge. The results in the
      theory of diagnosis and in model-based reasoning (MBR) obtained in early 1990s
      are used for providing a formal characterization of the notion of diagnosis and
      of the reasoning mechanisms used in CHECK. The paper addresses also the problem
      of replacing heuristic knowledge provided by human experts with operational
      knowledge automatically derived from the deep model. In particular, the pros and
      cons of knowledge compilation and of the integration of case-based reasoning
      (CBR) with MBR are discussed by summarizing the experience gained in developing
      AID and ADAPtER. The problem of using an explicit representation of time in
      diagnostic systems is analyzed and recent work on the different characterizations
      of diagnosis arising when the temporal dimension is considered is reported.
      Finally, the implications of the results obtained in MBR and in temporal
      reasoning on the future of medical diagnostic systems are briefly discussed.

PMID- 11470217
TI  - Medical informatics: reasoning methods.
AB  - The progress of medical informatics has been characterized by the development of
      a wide range of reasoning methods. These reasoning methods are based on
      organizing principles that make use of the various relations existing in medical
      domains: associations, probabilities, causality, functional relationships,
      temporal relations, locality, similarity, and clinical practice. Some, such as
      those based on associations and probabilities have been developed to the point
      where there are off-the-shelf tools available for the researcher to develop new
      decision support tools. Others such as temporal relations require more effort to
      use effectively. Even so, we have learned the importance of a separate explicit
      representation of the domain knowledge and have considerable experience and an
      impressive armamentarium with which to face the new milieu provided by the
      Internet.

PMID- 11470218
TI  - Machine learning for medical diagnosis: history, state of the art and
      perspective.
AB  - The paper provides an overview of the development of intelligent data analysis in
      medicine from a machine learning perspective: a historical view, a state-of-the
      art view, and a view on some future trends in this subfield of applied artificial
      intelligence. The paper is not intended to provide a comprehensive overview but
      rather describes some subareas and directions which from my personal point of
      view seem to be important for applying machine learning in medical diagnosis. In
      the historical overview, I emphasize the naive Bayesian classifier, neural
      networks and decision trees. I present a comparison of some state-of-the-art
      systems, representatives from each branch of machine learning, when applied to
      several medical diagnostic tasks. The future trends are illustrated by two case
      studies. The first describes a recently developed method for dealing with
      reliability of decisions of classifiers, which seems to be promising for
      intelligent data analysis in medicine. The second describes an approach to using
      machine learning in order to verify some unexplained phenomena from complementary
      medicine, which is not (yet) approved by the orthodox medical community but could
      in the future play an important role in overall medical diagnosis and treatment.

PMID- 11470219
TI  - AIM: a personal view of where I have been and where we might be going.
AB  - My own career in medical informatics and AI in medicine has oscillated between
      concerns with medical records and concerns with knowledge representation with
      decision support as a pivotal integrating issue. It has focused on using AI to
      organise information and reduce 'muddle' and improve the user interfaces to
      produce 'useful and usable systems' to help doctors with a 'humanly impossible
      task'. Increasingly knowledge representation and ontologies have become the
      fulcrum for orchestrating re-use of information and integration of systems.
      Encouragingly, the dilemma between computational tractability and expressiveness
      is lessening, and ontologies and description logics are joining the mainstream
      both in AI in Medicine and in Intelligent Information Management generally. It
      has been shown possible to scale up ontologies to meet medical needs, and
      increasingly ontologies are playing a key role in meeting the requirements to
      scale up the complexity of clinical systems to meet the ever increasing demands
      brought about by new emphasis on reduction of errors, clinical accountability,
      and the explosion of knowledge on the Web.

PMID- 11470220
TI  - General practitioner services in primary care groups in England: is there
      inequity between service availability and population need?
AB  - This study examined the coverage of minor surgery, child health surveillance and
      chronic disease management for asthma and diabetes in relation to population need
      and key organisational features of general practice in the 481 primary care
      groups (PCGs) in England. PCG-level summary scores were developed to estimate the
      relative availability of all four services and their relative importance in
      discriminating between high and low levels of service provision. The coverage of
      services was widespread and, in such circumstances, there was no systematic
      evidence of poorer service availability for PCGs with higher population need (the
      'inverse care' law). Rather this relation was localised, being most predominant
      for PCGs covering London and its suburbs. In these PCGs, there was no association
      between indicators of lack of capacity, such as single-handed practice, and
      levels of service provision.

PMID- 11470221
TI  - Small-area variation in mortality in the city of Oulu, Finland, during the period
      1978--1995.
AB  - The aim of the present work was to explore small-area differences in mortality
      from all causes among males and females within the city of Oulu during the period
      1978--1995 and to identify areas where mortality has been persistently high or
      low. Analyses carried out using Geographical Information System techniques with
      geo-referenced mortality data produced at a resolution of 1 x 1 km showed
      significant regional variations in mortality within the city. The differences
      were wide enough to suggest variations of several years in longevity, and were
      probably indicative of marked variations in the incidences of diseases. Observed
      mortality differences may reflect the influence of the rapidly changing urban
      structure and consequent health effects based on selection, lifestyles, work
      exposures and deprivation.

PMID- 11470222
TI  - Back to the old house? 'Sick role' and biographical narratives of the housing
      needs of short-stay hospital patients.
AB  - This paper examines how decisions are made about the housing needs of short-stay
      hospital patients. Two narrative types of patients' housing needs are identified.
      The 'sick role' narrative emphasised patients' ongoing medical needs and tended
      to prescribe 'sick role' placements in residential care or nursing homes instead
      of a return home. Conversely, the biographical narrative emphasised the
      importance of home as an integral element of 'elective biography' (Beck and Beck
      Gernsheim, in: Heelas, Lash and Morris (Eds.), Detraditionalization, Blackwell,
      Oxford, 1996) and thus a highly emotional 'psychic warehouse' (Gurney, Ph.D.
      Thesis, Bristol, 1996) that was integral to post-discharge recovery and well
      being.

PMID- 11470223
TI  - Neighbourhood renewal and health: evidence from a local case study.
AB  - This article presents findings from a before-and-after study of the effects of
      neighbourhood renewal on residents' health. Survey data were analysed using
      multivariate logistic regression. Before the renewal programme, damp and draughts
      had significant independent effects on respiratory health problems. Draughts and
      perceived community safety were associated with mental health problems.
      Children's mental health was associated with parental mental health. Following
      the renewal work, improvements occurred in both adults' and children's mental
      health, and smoking declined sharply. Respiratory health did not improve and
      there was no change in use of health services. Neighbourhood renewal in deprived
      areas can have an important role in improving community health.

PMID- 11470224
TI  - The fear of crime and area differences in health.
AB  - A number of studies have shown that major health inequalities exist between
      different areas within the UK. However, there has been some debate about the
      mechanisms underlying area differences in health. One of the mechanisms which
      could explain area differences in health is the fear of crime in the local area
      or neighbourhood. This study examines data from the 1996 British Crime Survey
      (N=16,090). The fear of crime was found to be associated with self-rated health
      even after adjusting for health behaviours and a number of individual and
      household level socio-economic factors. Area differences in self-rated health
      were reduced to non-significance after health behaviours, socio-economic factors
      and the fear of crime were adjusted for in the regression model. There is some
      evidence that fear of crime is associated with health and it may have an
      important role in explaining area differences in health.

PMID- 11470225
TI  - Characteristics of individuals and characteristics of areas: investigating their
      influence on health in the Whitehall II study.
AB  - There is evidence that health is determined by macro-level factors as well as by
      individual risk factors. Using data from the Whitehall II study we consider area
      level determinants of health and ask two related questions. Firstly, are health
      differences between areas explained by the individual risk profiles of residents
      in those areas? Secondly, since poorer people tend to live in poorer places, are
      individual socio-economic effects on health explained by where people live? The
      demographic characteristics of residents, level of deprivation in the area,
      housing and neighbourhood quality and social integration were independently
      associated with health but did not fully explain differences between areas.
      Although there was considerable residential polarisation, area deprivation did
      not explain why lower status participants had poorer health.

PMID- 11470226
TI  - Vasectomy and prostate cancer in Quebec, Canada.
AB  - The present investigation measured the association between vasectomy and prostate
      cancer (PC) in the male population of Quebec, Canada. The Quebec Health Insurance
      Board and the Quebec Cancer Registry were our principal sources of information.
      Lung cancer cases and the male population of Quebec served as controls for
      comparative purposes. Within a retrospective design, our preliminary results
      indicate an association between vasectomy and PC. Among the 1925-39 birth cohort
      of individuals diagnosed with PC in 1990--93, the global odds ratio was 2.6 (95%
      CI=1.7--4.3) while it was compared with lung cancer as the control group. This
      risk increased with the length of time between vasectomy and the diagnosis of
      cancer. An historical design indicated strong cohesion of the results. Besides,
      the risk does not vary when we control for the place of residence of the
      individuals. Vasectomy seems to increase the risk of PC at least 10 years after
      the operation, but we cannot exclude the impact of a possible detection bias
      among vasectomized individuals.

PMID- 11470227
TI  - Coping with the costs of primary care? Household and locational variations in the
      survival strategies of the urban poor.
AB  - This paper examines the 'survival' strategies adopted by lower income groups
      seeking to cope with the costs of primary care. Two surveys, one of the health
      and health service concerns of clients of an inner city voluntary welfare agency,
      and another of how 114 general practitioner (GP) surgeries in Christchurch, New
      Zealand aided patients in financial distress, were conducted in October-December,
      1997. Patients adopted a variety of strategies, both active and passive, with
      delays in obtaining medications and seeking financial help from GPs being the
      most common. Although less important, high rates of switching GPs occurred. There
      was evidence of geographical variation in the strategies adopted by patients and
      practices as well as of the effects of such strategies given that considerable
      levels of unmet need remain. I conclude that more attention should be paid to the
      gatekeeper role of GPs and how their actions in different social contexts may
      result in inequalities in service provision to low income patients and outcomes
      of care.

PMID- 11470228
TI  - p73.
AB  - The discovery of p73 as a family member of p53 has instigated a number of studies
      in search of its function, regulation, and involvement in tumorigenesis. p73 has
      been identified as a transcription factor that can regulate p53-dependent
      transcriptional targets. Similarly to p53, p73 can induce apoptosis in response
      to various stimuli, including certain types of DNA damage. This evidence suggests
      that p73 may act as a tumor suppressor with overlapping functions of p53. While
      mutations of p73 appear rare in human tumors, some leukemias have shown silencing
      of the gene by hypermethylation. Thus, introduction of p73 into tumor cells
      possessing inactive p53 may provide a valuable therapeutic approach.

PMID- 11470229
TI  - Chemistry and biology of eukaryotic iron metabolism.
AB  - With rare exceptions, virtually all studied organisms from Archaea to man are
      dependent on iron for survival. Despite the ubiquitous distribution and abundance
      of iron in the biosphere, iron-dependent life must contend with the paradoxical
      hazards of iron deficiency and iron overload, each with its serious or fatal
      consequences. Homeostatic mechanisms regulating the absorption, transport,
      storage and mobilization of cellular iron are therefore of critical importance in
      iron metabolism, and a rich biology and chemistry underlie all of these
      mechanisms. A coherent understanding of that biology and chemistry is now rapidly
      emerging. In this review we will emphasize discoveries of the past decade, which
      have brought a revolution to the understanding of the molecular events in iron
      metabolism. Of central importance has been the discovery of new proteins carrying
      out functions previously suspected but not understood or, more interestingly,
      unsuspected and surprising. Parallel discoveries have delineated regulatory
      mechanisms controlling the expression of proteins long known--the transferrin
      receptor and ferritin--as well as proteins new to the scene of iron metabolism
      and its homeostatic control. These proteins include the iron regulatory proteins
      (IRPs 1 and 2), a variety of ferrireductases in yeast an mammalian cells,
      membrane transporters (DMT1 and ferroportin 1), a multicopper ferroxidase
      involved in iron export from cells (hephaestin), and regulators of mitochondrial
      iron balance (frataxin and MFT). Experimental models, making use of organisms
      from yeast through the zebrafish to rodents have asserted their power in
      elucidating normal iron metabolism, as well as its genetic disorders and their
      underlying molecular defects. Iron absorption, previously poorly understood, is
      now a fruitful subject for research and well on its way to detailed elucidation.
      The long-sought hemochromatosis gene has been found, and active research is
      underway to determine how its aberrant functioning results in disease that is
      easily controlled but lethal when untreated. A surprising connection between iron
      metabolism and Friedreich's ataxia has been uncovered. It is no exaggeration to
      say that the new understanding of iron metabolism in health and disease has been
      explosive, and that what is past is likely to be prologue to what is ahead.

PMID- 11470230
TI  - Human endothelial gelatinases and angiogenesis.
AB  - Endothelial cell invasion is an essential event during angiogenesis (formation of
      new blood vessels). The process involves the degradation of the basement membrane
      and the underlying interstitium. The matrix metalloproteinase (MMP) family is
      considered to be primarily responsible for matrix degradation. Two members of the
      family, gelatinase A and B play an important role in angiogenesis. This review
      outlines recent findings on their regulation in human endothelial cells. Latent
      gelatinase B is secreted from endothelial cells. This enzyme can also accumulate
      in the cytosol as an active enzyme, free of TIMP-1. In contrast, latent
      gelatinase A is constitutively secreted from the cells. Unlike other MMPs,
      gelatinase A activation occurs on the cell membrane and is mediated by MT1-MMP. A
      number of physiological activators have recently been described. These include
      thrombin and activated protein C, both of which activate gelatinase A independent
      of the MT1-MMP pathway. These new findings may lead to therapeutic interventions
      for the treatment of angiogenic-dependent diseases such as cancer and arthritis.

PMID- 11470231
TI  - Transforming growth factor beta1 mediates hypopigmentation of B16 mouse melanoma
      cells by inhibition of melanin formation and melanosome maturation.
AB  - Transforming growth factor-beta1 (TGFbeta1) downregulates tyrosinase in B16
      melanoma cells by decreasing gene expression and the intracellular half-life of
      the enzyme, but does not block tyrosinase stimulation by alpha-melanocyte
      stimulating hormone (alphaMSH). In the presence of both agents, the enzymatic
      activity is intermediate between the one of cells treated with either agent
      alone. Here we show that TGFbeta1 equally inhibits the melanogenic activities of
      melan-a melanocytes and B16 melanoma cells, thus validating the B16 model. In
      both cell types, TGFbeta1 (10(-10) M, 48 h) inhibited to comparable levels
      tyrosine hydroxylation and melanin formation from L-tyrosine. Thus, the
      inhibitory effect is exerted mainly at the rate limiting step of the pathway. By
      means of quantitative image analysis techniques, we also studied the effects of
      TGFbeta1 and alphaMSH on melanosome number, volume density and maturation degree.
      alphaMSH (10(-7) M, 48 h) increased 7-fold melanosome volume density, whereas
      TGFbeta1 by itself had no significant effect. However, melanosomal volume density
      was intermediate in cells treated with both agents, as compared to control or
      alphaMSH-treated cells. Moreover, TGFbeta1 blocked the alphaMSH-elicited increase
      in the number of melanosomes. Control and alphaMSH-treated melanocytes contained
      more stage I+II premelanosomes and stage IV, fully melanized organelles than
      partially melanized stage III melanosomes. TGFbeta1 increased the percentage of
      stage III melanosomes. This trend was even more marked in cells treated with
      alphaMSH and TGFbeta1. The accumulation of incompletely melanized melanosomes is
      consistent with the inhibition of melanin formation activity by TGFbeta1 and with
      its hypopigmenting effect.

PMID- 11470232
TI  - Expression of the mRNA (N6-adenosine)-methyltransferase S-adenosyl-L-methionine
      binding subunit mRNA in cultured cells.
AB  - Ribonuclease protection assays (RPA) were used to detect and quantitate the
      amount of messenger RNA (mRNA) coding for the S-adenosyl-L-methionine binding
      subunit (MT-A70) of the mRNA (N6-adenosine)-methyltransferase from different
      types of cultured cells. HeLa cells cultured in suspension were analyzed at
      regular intervals along a normal growth curve. It was discovered that MT-A70 mRNA
      was transcribed constitutively across the time-course, irrespective of the rate
      of cellular proliferation. Further, 11 different cell lines representing non
      tumorigenic, tumorigenic, and virally-transformed tumorigenic types from Homo
      sapiens, Mus musculus, and Rattus norvegicus were examined for MT-A70 mRNA
      expression. It was found that all the cell lines expressed a long and short
      splice-variant form of the gene. In general, the cell lines expressed a similar
      total amount of the MT-A70 mRNA while statistically significant differences
      existed between the quantity of the long and short forms among cell types.
      Tumorigenic cell lines synthesized as much as a 9-fold greater amount of long
      form versus short form MT-A70 mRNA. Comparatively, non-tumorigenic cell lines
      generally expressed only a 1.5-fold greater amount of long form versus short form
      MT-A70 mRNA.

PMID- 11470233
TI  - Retinol mobilization from cultured rat hepatic stellate cells does not require
      retinol binding protein synthesis and secretion.
AB  - Retinol mobilization from retinyl esters stores of hepatic stellate cells (HSCs)
      is a key step in the regulation of mammalian retinol homeostasis, but the precise
      mechanisms of such a mobilization are still poorly understood. Using primary
      cultures of HSCs, we first demonstrated that HSCs expressed immunoreactivity
      against retinol-binding-protein (RBP) when cultured in a medium containing RBP
      but were unable to synthesize RBP transcripts and proteins. Using pulse and chase
      type experiments, we demonstrated that radioactive retinol was released in
      culture medium without binding proteins. Inhibition of protein secretion by
      brefeldin A did not modify quantitatively retinol release. This data ruled out,
      for the first time, the direct involvement of RBP in retinol mobilization from
      HSCs. Moreover, HSCs co-cultured with primary isolated hepatocytes displayed an
      increase of retinol transfer from HSCs to hepatocytes when they established
      direct physical contacts, as compared with co-cultures without contact. Based on
      this latter data, a mechanism of retinol mobilization from HSCs via the
      hepatocytes using retinol transfer through cellular membranes is proposed.

PMID- 11470234
TI  - Skeletal muscle protein loss due to D-penicillamine results from reduced protein
      synthesis.
AB  - Reports in the literature indicate that the trifunctional amino acid D
      penicillamine (D-P) induces a variety of muscle abnormalities, although the
      mechanisms are unknown. We hypothesised that defects may also arise due to the
      effects of D-P on rates of protein synthesis, possibly via changes in muscle
      metal composition. Male Wistar rats were injected with D-P at doses of 50 and 500
      mg/kg body weight, i.p. Rats designated as controls were injected with 0.15 mol/l
      NaCl. After 24 h, there were reductions in muscle protein contents, protein
      synthetic capacities (RNA:protein ratio), fractional rates of protein synthesis,
      synthesis rates per unit RNA and synthesis rates per unit DNA in skeletal muscles
      of D-P treated rats. There were no statistically significant differences between
      the responses of the muscles containing a predominance of either Type I
      (represented by the soleus) or Type II (represented by the plantaris) fibres. In
      general, intracellular amino acids were not significantly affected by D-P
      treatment. Changes in muscle metals included significant reductions in copper,
      iron and manganese, without alterations in zinc or magnesium. In liver D-P
      reduced copper and iron though zinc, manganese and magnesium were unaffected.
      These effects of D-P on muscle may have been direct, as plasma indices of liver
      (activities of alkaline phosphatase and alanine aminotransferase) and kidney
      (urea, creatinine and electrolytes) damage were not significantly altered by D-P
      treatment. Plasma levels of corticosterone, insulin and free T3 were also not
      significantly affected by D-P treatment. Muscle protein carbonyl concentrations,
      an index of free radical activity, were similarly unaffected. This is the first
      report of reduced rates of muscle protein synthesis in D-P treatment. Our data
      suggests that the reduced rates of muscle protein synthesis may contribute to, or
      reflect, the muscle abnormalities observed in patients undergoing D-P treatment.

PMID- 11470235
TI  - The closely related POU family transcription factors Brn-3a and Brn-3b are
      expressed in distinct cell types in the testis.
AB  - Although the Brn-3a and Brn-3b POU family transcription factors were originally
      identified in neuronal cells, their expression in some non neuronal cell types
      has previously been reported. Here we report that Brn-3a and Brn-3b are also
      expressed in the testis with expression of each factor being observed at distinct
      stages of germ cell development. Thus, Brn-3a is expressed in spermatogonia
      whereas Brn-3b expression is observed in post-meiotic spermatids. In agreement
      with this, Brn-3a expression is detectable much earlier than that of Brn-3b in
      testes derived from sexually immature postnatal animals. Similarly, Brn-3b
      expression is absent in knock out mice lacking a functional CREM transcription
      factor in which the later stages of germ cell development do not occur, whereas
      Brn-3a expression is observed at similar levels in the testes of these knock out
      mice. Interestingly, the cellular pattern of Brn-3a expression during germ cell
      development coincides with that of the BRCA-1 anti-oncogene. Consistent with the
      possibility that Brn-3a may regulate expression of BRCA-1 in the testis, we have
      shown that Brn-3a can strongly activate the BRCA-1 promoter in co-transfection
      experiments whereas Brn-3b does not have this effect. Hence, as observed in
      neuronal cells, Brn-3a and Brn-3b may play distinct and important functional
      roles in the regulation of gene expression during germ cell development.

PMID- 11470236
TI  - Role of sphingolipids in the biogenesis of membrane domains.
AB  - In recent years, a huge interest in sphingolipid- and cholesterol-enriched
      membrane domains has risen, after their involvement in fundamental membrane
      associated events such as signal transmission, cell adhesion and lipid/protein
      sorting was postulated. Theoretical considerations and several experimental data
      suggest that sphingolipids play an important role in the biogenesis and function
      of domains. In fact, their physicochemical features, different from those of
      other membrane lipids, allow their interaction either with other sphingolipids or
      with other membrane components and external ligands. Owing to these features,
      sphingolipids may undergo segregation and represent a nucleation point for co
      clustering with other lipids and proteins in a complex, functional domain.
      Moreover, sphingolipids confer dynamic properties on domains, a fundamental
      feature for the modulation of their postulated functions.

PMID- 11470237
TI  - The cloning and expression of a murine triacylglycerol hydrolase cDNA and the
      structure of its corresponding gene.
AB  - A novel murine cDNA for triacylglycerol hydrolase (TGH), an enzyme that is
      involved in mobilization of triacylglycerol from storage pools in hepatocytes,
      has been cloned and expressed. The cDNA consists of 1962 bp with an open reading
      frame of 1695 bp that encodes a protein of 565 amino acids. Murine TGH is a
      member of the CES1A class of carboxylesterases and shows a significant degree of
      identity to other carboxylesterases from rat, monkey and human. Expression of the
      cDNA in McArdle RH7777 hepatoma cells showed a 3-fold increase in the hydrolysis
      of p-nitrophenyl laurate compared to vector-transfected cells. The highest
      expression of TGH was observed in the livers of mice, with lower expression in
      kidney, heart, adipose and intestinal (duodenum/jejunum) tissues. The murine gene
      that encodes TGH was cloned and exon-intron boundaries were determined. The gene
      spans approx. 35 kb and contains 14 exons. The results will permit future studies
      on the function of this gene via gene-targeting experiments and analysis of
      transcriptional regulation of the TGH gene.

PMID- 11470238
TI  - Progesterone inhibits apolipoprotein-mediated cellular lipid release: a putative
      mechanism for the decrease of high-density lipoprotein.
AB  - In order to investigate the mechanism for female gonadal hormones to regulate the
      plasma high-density lipoprotein (HDL) level, the effect of 17 beta-estradiol and
      progestogens was examined in vitro on the assembly of HDL by free apolipoprotein
      A-I (apoA-I) with cellular cholesterol and phospholipid. ApoA-I generated HDL
      particles by removing cholesterol and phospholipid from human fibroblasts, MRC-5.
      While 17 beta-estradiol did not influence this reaction, progesterone suppressed
      the removal by apoA-I of both cholesterol and phospholipid, with the extent of
      the inhibition more for cholesterol than phospholipid. Three other synthetic
      progestogens showed the similar inhibitory effect on the cellular cholesterol
      release. Cellular cholesterol de novo-synthesized from mevalonolactone entered
      more into the acyl-esterified cholesterol compartment and less to the
      unesterified compartment in the presence of progesterone. On the other hand,
      progesterone did not influence the overall mass ratio of free and esterified
      cholesterol in the cell. Cell-surface cholesterol was also uninfluenced by
      progesterone when probed by extracellular cholesterol oxidase reaction or by
      diffusion-mediated cellular cholesterol release to cyclodextrin. Neither caveolin
      1 nor ABCA1 expression was influenced by progesterone. Progesterone thus seems
      primarily to alter the specific intracellular cholesterol compartment that is
      related to the apoA-I-mediated HDL assembly. This mechanism might contribute to
      the decrease of plasma HDL by administration of progestogen in women under
      hormone replacement therapy.

PMID- 11470239
TI  - Dose-dependent effects of lovastatin on cell cycle progression. Distinct
      requirement of cholesterol and non-sterol mevalonate derivatives.
AB  - The mevalonate pathway is tightly linked to cell proliferation. The aim of the
      present study is to determine the relationship between the inhibition of this
      pathway by lovastatin and the cell cycle. HL-60 and MOLT-4 human cell lines were
      cultured in a cholesterol-free medium and treated with increasing concentrations
      of lovastatin, and their effects on cell proliferation and the cell cycle were
      analyzed. Lovastatin was much more efficient in inhibiting cholesterol
      biosynthesis than protein prenylation. As a result of this, lovastatin blocked
      cell proliferation at any concentration used, but its effects on cell cycle
      distribution varied. At relatively low lovastatin concentrations (less than 10
      microM), cells accumulated preferentially in G(2) phase, an effect which was both
      prevented and reversed by low-density lipoprotein cholesterol. At higher
      concentrations (50 microM), the cell cycle was also arrested at G(1) phase. In
      cells treated with lovastatin, those arrested at G(1) progressed through S upon
      mevalonate provision, whereas cholesterol supply allowed cells arrested at G(2)
      to traverse M phase. These results demonstrate the distinct roles of mevalonate,
      or its non-sterol derivatives, and cholesterol in cell cycle progression, both
      being required for normal cell cycling.

PMID- 11470240
TI  - Uncoupling protein-3 mRNA up-regulation in C2C12 myotubes after etomoxir
      treatment.
AB  - Uncoupling proteins (UCPs) are mitochondrial membrane proton transporters that
      uncouple respiration from oxidative phosphorylation by dissipating the proton
      gradient across the membrane. Treatment of C2C12 myotubes for 24 h with 40 microM
      etomoxir, an irreversible inhibitor of carnitine palmitoyltransferase I (CPT-I),
      up-regulated uncoupling protein 3 (UCP-3) mRNA levels (2-fold induction), whereas
      UCP-2 mRNA levels were not modified. Etomoxir treatment also caused a 2.5-fold
      induction in M-CPT-I (muscle-type CPT-I) mRNA levels. In contrast, other well
      known peroxisome proliferator-activated receptor alpha (PPAR alpha) target genes,
      such as acyl-CoA oxidase and medium-chain acyl-CoA dehydrogenase, were not
      affected, suggesting that this transcription factor was not involved in the
      effects of etomoxir. Since it has been reported that CPT-I inhibition by etomoxir
      leads to a further increase in ceramide synthesis, we test the possibility that
      ceramides were involved in the changes reported. Similarly to etomoxir, addition
      of 20 microM C(2)-ceramide to C2C12 myotubes for 3, 6 and 9 h resulted in
      increased UCP-3 and M-CPT-I mRNA levels. These results indicate that the effects
      on UCP-3 mRNA levels could be mediated by increased ceramide synthesis.

PMID- 11470241
TI  - Enhanced free radical scavenging and decreased lipid peroxidation in the rat
      fetal brain after treatment with ethyl docosahexaenoate.
AB  - In order to explore possible mechanisms to explain previously observed decreases
      in fetal brain lipid peroxidation (LPO) following intraamniotic administration of
      ethyl docosahexaenoate (Et-DHA) to near term fetuses, the hydroxyl radical
      trapping capacity of Et-DHA treated fetal brain preparations was compared to
      control ethyl oleate injected fetuses by electron spin resonance using 5,5'
      dimethyl-1-pyrroline N-oxide (DMPO) probe. Lipid extracts from control brains
      showed little hydroxyl radical scavenging activity, whereas those from the Et-DHA
      injected animals exhibited an almost 70% decrease in the amount of DMPO-OH
      adducts. A marked decrease (58%) in LPO formation was noticed in the Et-DHA
      treated animals compared to controls. The Et-DHA treatment related trapping
      capacity resided in the phospholipid fraction of the lipid extract, which was
      enriched in both docosahexaenoic acid and aminophospholipid contents. The
      decreased LPO production, as well as increased production of prostaglandin E(2)
      and nitric oxide by the fetal brain following Et-DHA administration, could be
      mimicked by a synthetic quinone possessing both hydroxyl radical producing and
      LPO propagation inhibiting properties. The data are consistent with the
      possibility that the neuroprotective effect of Et-DHA might be due to possible
      free radical scavenging ability of the brain tissue and interference with LPO
      propagation.

PMID- 11470242
TI  - Transcriptional regulation of the lung fatty acid synthase gene by
      glucocorticoid, thyroid hormone and transforming growth factor-beta 1.
AB  - Fatty acid synthase (FAS) is a key enzyme in the biosynthesis of lung surfactant.
      FAS expression in fetal lungs is increased by glucocorticoids and this effect is
      largely due to increased transcription. The stimulatory effect of glucocorticoid
      on FAS expression is antagonized by thyroid hormone and transforming growth
      factor-beta 1 (TGF-beta 1). To determine the glucocorticoid responsive regions of
      the FAS gene we employed deletion analysis and reporter gene assays. A549 cells
      were transfected with various FAS gene constructs ligated to the firefly
      luciferase gene and cultured with dexamethasone (Dex) for 24 h after which
      luciferase activity was measured. Dex increased luciferase expression in response
      to a fragment in the promoter and 5'-flanking region of the FAS gene, from -1592
      to +65 bp. This increase was antagonized by triiodothyronine (T(3)) and TGF-beta
      1. Serial deletions showed that the full response to Dex and T(3) were retained
      in the 89 bp -33/+56 bp fragment whereas the response to TGF was mediated by the
      immediately upstream -104/-34 bp sequence. The Dex responsive region of the FAS
      gene could not be separated from the minimal promoter showing that they are
      intimately associated. The extents of Dex stimulation and antagonism by T(3) and
      TGF in A549 cells were similar to those noted on parameters of FAS expression in
      fetal lung explants. These data show that the effects of Dex, T(3) and TGF on FAS
      expression are mediated by DNA sequences in the promoter region of the gene.

PMID- 11470243
TI  - Very-long-chain fatty acid-containing phospholipids accumulate in fatty acid
      synthase temperature-sensitive mutant strains of the fission yeast
      Schizosaccharomyces pombe fas2/lsd1.
AB  - Fission yeast lsd1 strains show aberrant mitosis with a lsd phenotype, large and
      small daughter nuclei, and a very thick septum, the phenotypic expression being
      temperature-sensitive. The lsd1(+) gene is the homologue of the budding yeast
      FAS2 gene encoding the fatty acid synthase alpha-subunit as reported previously
      (S. Saitoh, K. Takahashi, K. Nabeshima, Y. Yamashita, Y. Nakaseko, A. Hirata, M.
      Yanagida, J. Cell Biol. 134 (1996) 949--961). In this paper, lsd1 is considered
      to represent fas2. Here, three fas2 strains were investigated and found to have
      missense point mutations at different sites in the gene encoding the alpha
      subunit of fatty acid synthase. The mutation affected only slightly the enzymatic
      activities monitored in vitro. Unexpectedly, abnormal phospholipids,
      phosphatidylcholine and phosphatidylethanolamine, both of which contain a very
      long-chain fatty acyl residue (1-melissoyl-2-oleolyl-sn-glycero-3-phosphocholine
      and 1-melissoyl-2-oleolyl-sn-glycero-3-phosphoethanolamine), accumulated in fas2
      strains in a temperature-sensitive manner. Rescue of the fas2 strains by addition
      of palmitate to the medium at restrictive temperature was accompanied by
      disappearance of these abnormal phospholipids. Accumulation of these lipids in
      membranes may cause alteration of various cellular functions.

PMID- 11470244
TI  - A genetic screen for ethanolamine auxotrophs in Saccharomyces cerevisiae
      identifies a novel mutation in Mcd4p, a protein implicated in
      glycosylphosphatidylinositol anchor synthesis.
AB  - A genetic screen for ethanolamine auxotrophs has identified a novel mutant allele
      of the morphogenesis checkpoint dependent (MCD)-4 gene, designated mcd4-P301L. In
      the presence of a null allele for the phosphatidylserine (PtdSer) decarboxylase 1
      gene (psd1 Delta), the mcd4-P301L mutation confers temperature sensitivity for
      growth on minimal medium. This growth defect is reversed by either ethanolamine
      or choline supplementation. Incubation of mutant cells with [(3)H]serine followed
      by analysis of the aminoglycerophospholipids demonstrated a 60% decrease in
      phosphatidylethanolamine (PtdEtn) formation compared to parental cells. Chemical
      analysis of phospholipid content after culture under non-permissive conditions
      also demonstrated a 60% decrease in the PtdEtn pool compared to the parental
      strain. Although the morphogenesis checkpoint dependent (MCD)-4 gene and its
      homologues have been shown to play a role in glycosylphosphatidylinositol (GPI)
      anchor synthesis, the mcd4-P301L strain displayed normal incorporation of
      [(3)H]inositol into both proteins and lipids. Thus, a defect in GPI anchor
      synthesis does not explain either the ethanolamine auxotrophy or biochemical
      phenotype of this mutant. We also examined the growth characteristics and PtdSer
      metabolism of a previously described mcd4-174 mutant strain, with defects in GPI
      anchor synthesis, protein modification and cell wall maintenance. The mcd4-174,
      psd1 Delta strain is a temperature sensitive ethanolamine auxotroph that requires
      osmotic support for growth, and displays normal PtdEtn formation compared to
      parental cells. These results reveal important genetic interactions between PSD1
      and MCD4 genes, and provide evidence that Mcd4p can modulate
      aminoglycerophospholipid metabolism, in a way independent of its role in GPI
      anchor synthesis.

PMID- 11470245
TI  - Galactose dialdehyde: the forgotten candidate for a protein cross-linker?
AB  - Oxidation of D-galactose mediated by D-galactose oxidase [EC 1.1.3.9] gave a
      dialdehyde that occurs as two bicyclic structures in aqueous solution as
      established by 13C labeling and NMR spectroscopy. The dialdehyde is very reactive
      at basic pH leading to complex reaction mixtures. A comparison was made with
      glutaraldehyde to assess its potential as protein cross-linker.

PMID- 11470246
TI  - Syntheses of model compounds related to an antigenic epitope in pectic
      polysaccharides from Bupleurum falcatum L.
AB  - Stereocontrolled syntheses of model compounds related to a category of the major
      antigenic epitope against anti-bupleurum 2IIc/PG-1-IgG from an anti-ulcer pectic
      polysaccharide are described. Glycosylation of the glucuronic acid donors
      methyl(2,3-di-O-benzoyl-4-O-methyl-alpha-D-glucopyranosyl
      trichloroacetimidate)uronate and methyl (2,3-di-O-benzoyl-4-O-methyl-beta-D
      glucopyranosyl)uronate-(1-->6)-2,3,4-tri-O-benzoyl-alpha-D-galactopyranosyl
      trichloroacetimidate with the common acceptor 2-(trimethylsilyl)ethyl 2,3,4-tri-O
      benzyl-beta-D-galactopyranoside in the presence of trimethylsilyl triflate
      (TMSOTf) gave the desired di- and trisaccharide derivatives. Furthermore the
      products were transformed into the oligo-valent clustering saccharides, N,N',N"
      tri-(5-[4-O-methyl-beta-D-glucopyranosyluronic acid-(1-->6)-beta-D
      galactopyranosyloxy]pentylcarbonylaminoethyl)-1,3,5-benzenetriamide and N,N',N"
      tri-(5-[4-O-methyl-beta-D-glucopyranosyluronic acid (1-->6)-beta-D
      galactopyranosyl-(1-->6)-beta-D-galactopyranosyloxy]pentylcarbonylaminoethyl)
      1,3,5-benzenetriamide.

PMID- 11470247
TI  - Water-soluble and water-insoluble glucans produced by Escherichia coli
      recombinant dextransucrases from Leuconostoc mesenteroides NRRL B-512F.
AB  - Two dextransucrase genes, dsrS and dsrT5, from Leuconostoc mesenteroides NRRL B
      512F were expressed in Escherichia coli, and recombinant dsrT5 dextransucrase was
      shown to produce a water-insoluble glucan. In contrast, native dextran from L.
      mesenteroides B-512F is water-soluble. The water-insoluble glucan was shown by
      13C NMR and glycosyl-linkage composition analysis to contain about 50% 6-linked
      Glcp and 40% 3-linked Glcp. The 'primitive' B-512F strain is suggested to have
      produced water-insoluble glucan containing 3-linked Glcp. The glucans produced by
      dextransucrases expressed in E. coli contained 4-linked Glcp, as shown by
      glycosyl-linkage composition analysis. The amount of 4-linked Glcp was increased
      when the truncated, water-insoluble, glucan-producing dextransucrase, which does
      not have C-terminal repeating units, was added to the water-soluble, glucan
      producing dextransucrase. Trace amounts of 4-linked Glcp were also detected in
      the dextran obtained from the B-512F culture supernatant, in dextran produced by
      dextransucrase purified from the B-512F strain culture supernatant, and in
      clinical dextran. The results of glycosyl-linkage composition analysis suggest
      that dextransucrases produce 4-linked Glcp as well as 6- and 3-linked Glcp.

PMID- 11470248
TI  - Effect of fiber orientation in dynamic FTIR study on native cellulose.
AB  - The properties of cellulose materials are highly dependent on the interactions
      between and within the cellulose chains mainly related to inter- and
      intramolecular hydrogen bonds. To investigate the deformation behavior of
      cellulose and its relation to molecular straining, cellulose sheets with
      different fiber orientations were studied by dynamic FTIR spectroscopy. The
      sheets were stretched sinusoidally at low strains while being irradiated with
      polarized infrared light. It is shown that the polarization direction determines
      the dynamic IR response to a higher extent than the fiber direction in the sample
      sheets. Different polarization modes give different dynamic signals, allowing
      conclusions to be drawn on the structural orientation of submolecular groups in
      the cellulose molecules. The bands in the spectra mainly affected by the
      deformation of the sheets were derived from skeletal vibrations that include the
      C-O-C bridge connecting adjacent rings and from the hydrogen bonds. The
      conclusion that these groups are the ones that are mainly deformed under load has
      thereby experimentally demonstrated the theoretical calculations from Tashiro and
      Kobayashi [Tashiro, K.; Kobayashi, M. Polymer 1991, 32, 1516-1526].

PMID- 11470249
TI  - Isolation and NMR characterization of rosacelose, a novel sulfated polysaccharide
      from the sponge Mixylla rosacea.
AB  - Rosacelose, a new anti-HIV polysaccharide composed of glucose and fucose sulfate,
      has been isolated from an aqueous extract of the marine sponge Mixylla rosacea.
      Extensive use of 1H and 13C multidimensional NMR spectroscopy, combined with
      chemical analysis were used to establish a linear polysaccharide structure
      composed mainly of 4,6-disulfated 3-O-glycosylated alpha-D-glucopyranosyl and 2,4
      disulfated 3-O-glycosylated alpha-L-fucopyranosyl residues (in a 3:1 molar
      ratio).

PMID- 11470250
TI  - Negative-ion electrospray ionisation-mass spectrometry (ESI-MS) as a tool for
      analysing structural heterogeneity in kappa-carrageenan oligosaccharides.
AB  - Oligosaccharides, enzymically produced from kappa-carrageenan, have been
      investigated by electrospray ionisation mass spectrometry (ESI-MS). The technique
      was used without prior derivatisation of the oligosaccharide originally obtained
      by size-exclusion chromatography (SEC). The structure of the oligosaccharides was
      mainly 4-sulphated neocarrabiose (A-G4S) with an increasing length ranging from
      di- to dodecasaccharides. However, in the larger oligosaccharides, structural
      motifs deviating from the perfect alternating A-G4S structure were detected, i.e.
      (A2S-G4S). Although resulting in reduced signal intensity, samples to which NaCl
      was added also gave rise to reliable mass spectra. Desulphation was induced at
      elevated cone voltages and in acidic or alkaline salt solutions.

PMID- 11470251
TI  - The cations and anions of cyclobutanetetraone poly(phenylhydrazones).
AB  - Six cyclobutanetetraone poly(arylhydrazones) have been treated with acids and
      bases, and the structures of the resulting anions and cations studied by UV-Vis
      absorption and NMR spectroscopy. In acid media, all the hydrazones studied formed
      cations, which exhibited bathochromic shifts due to the extension of their
      resonance systems. However, in bases, only some (those which could enolize)
      formed anions that exhibited hypsochromic shifts; the others were unaltered.

PMID- 11470252
TI  - Crystal structure and solid state 13C NMR analysis of N-(methyl 3,4,6-tri-O
      acetyl-alpha, and beta-D-glucopyranosid-2-yl)-oxamide derivative of p
      chloroaniline, N,N-diethylamine, N-methylaniline and N-ethylaniline.
AB  - The X-ray diffraction analysis of N-(methyl 3,4,6-tri-O-acetyl-alpha-D
      glucopyranosid-2-yl)-N'-p-chlorophenyloxamide (1), N-(methyl 3,4,6-tri-O-acetyl
      alpha-D-glucopyranosid-2-yl)-N',N'-diethyloxamide (2), N-acetyl, N-(methyl 3,4,6
      tri-O-acetyl-beta-D-glucopyranosid-2-yl), N'-methyl, N'-phenyloxamide (3), N
      acetyl, N-(methyl 3,4,6-tri-O-acetyl-beta-D-glucopyranosid-2-yl), N'-ethyl, N'
      phenyloxamide (4) was performed. It was found that the oxamide group in compounds
      1-4 can be characterized as two structurally independent amides because there is
      no pi conjugation across the oxalyl OC-CO bond. Only the oxamide group of 1 is
      planar and adopts trans conformation stabilized as two intramolecular N-H...O
      hydrogen bonds.

PMID- 11470254
TI  - Inhibitors of arachidonic acid metabolism potentiate tumour necrosis factor-alpha
      induced apoptosis in HL-60 cells.
AB  - We investigated whether and how could various modulators of arachidonic acid
      metabolism affect apoptosis induced by tumour necrosis factor-alpha (TNF-alpha)
      in human myeloid leukaemia HL-60 cells. These included arachinonyltrifluoromethyl
      ketone (AACOCF3; cytosolic phospholipase A2 inhibitor), indomethacin
      (cyclooxygenase inhibitor), MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5
      isopropylindol-2-yl]-2,2-dimethyl propanoic acid; 5-lipoxygenase-activating
      protein inhibitor), nordihydroguaiaretic acid (general lipoxygenase inhibitor),
      and arachidonic acid itself. Incubation of HL-60 cells with nordihydroguaiaretic
      acid resulted in apoptosis and it was characterised by mitochondria membrane
      depolarisation, release of cytochrome c from mitochondria into cytosol and
      activation of caspase-3. Indomethacin and nordihydroguaiaretic acid
      synergistically potentiated TNF-alpha-induced apoptosis, while arachidonic acid,
      AACOCF3 and MK-886 did not modulate its effects. Furthermore, indomethacin
      potentiated apoptosis in cells treated with a differentiating agent, all-trans
      retinoic acid, which induces resistance to TNF-alpha. However, the observed
      effects were probably not associated either with the cyclooxygenase- or
      lipoxygenase-dependent activities of indomethacin and nordihydroguaiaretic acid,
      respectively. Since indomethacin may reportedly activate peroxisome proliferator
      activated receptors (PPARs), the effects of specific ligands of PPARs on
      apoptosis were studied as well. It was found that selective PPARs ligands had no
      effects on TNF-alpha-induced apoptosis. The findings suggest that arachidonic
      acid metabolism does not play a key role in regulation of apoptosis induced by
      TNF-alpha in the present model. Nevertheless, our data raise the possibility that
      indomethacin could potentially be used to improve the treatment of human myeloid
      leukaemia.

PMID- 11470255
TI  - Agonist properties of pindolol at h5-HT1A receptors coupled to mitogen-activated
      protein kinase.
AB  - At h5-HT1A receptors, stably transfected into Chinese Hamster Ovary Cells (CHO-h5
      HT1A), the selective 5-HT1A receptor agonist, (+)8-hydroxy-dipropyl-amino
      tetralin, ((+)8-OH-DPAT), transiently activated mitogen-activated protein kinase
      (MAPK) with a pEC50 of 8.5. The arylalkylamine, (-)-pindolol, also behaved as an
      agonist with a maximal effect of 57% relative to (+)8-OH-DPAT (100%), and with a
      pEC50 of 7.2. The selective 5-HT(1A) receptor antagonist, N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-hexane carboxamide
      (WAY100,635), blocked (+)8-OH-DPAT- and (-)-pindolol-induced MAPK activation with
      pK(B)s of 9.7 and 9.9, respectively, whereas the selective 5-HT(1B) receptor
      antagonist, 1'-Methyl-5-[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4
      ylcarbonyl]-2,3,6,7-tetrahydro-5H-spiro[furo[2,3-f]indole-3,4'-piperidine]
      (SB224,289) was inactive. Pertussis toxin blocked the actions of (+)8-OH-DPAT and
      (-)-pindolol demonstrating implication of G(i)/G(o) proteins. Thus, stimulation
      of MAPK provides an intracellular marker and signal for expression of the agonist
      actions of (-)-pindolol at h5-HT1A receptors.

PMID- 11470256
TI  - [Ca2+]i-dependent actions of taurine in spontaneously beating rabbit sino-atrial
      nodal cells.
AB  - Modulation by taurine of the pacemaking activity and the underlying ionic
      currents in rabbit sino-atrial nodal cells was investigated at low and high
      cellular Ca2+ concentrations ([Ca2+]i) using a patch-clamp technique. At both pCa
      8 and 6, taurine depressed the spontaneous activity, more strongly at pCa 6 than
      at pCa 8. Taurine, 20 mM, markedly inhibited the L-type Ca2+ current: by 56.9+/
      2.8% (n=6, P<0.001) at pCa 8, and by 97.6+/-3.8% (n=7, P<0.001) at pCa 6. Also at
      20 mM, taurine decreased the delayed rectifier K+ current by 26.8+/-2.6% (n=6,
      P<0.01) at pCa 6, whereas taurine had less or no effect at pCa 8. The
      hyperpolarization-activated inward current also decreased at both pCa 8 and 6, by
      18.3+/-1.3% (n=8, P<0.05) and by 20.8+/-3.3% (n=8, P<0.05) in 20 mM taurine,
      respectively. Taurine caused a more potent inhibitory effect at pCa 6. Taurine
      often elicited dysrhythmias, at 20 mM, in 3 of 17 cells at pCa 8 and in 12 of 16
      cells at pCa 6. During washout, the incidence of dysrhythmias or arrest increased
      further. These results indicate that taurine exerts more potent inhibitory
      actions on ionic currents under Ca2+ overload conditions in rabbit sino-atrial
      nodal cells. However, taurine would possibly elicit a cellular Ca2+ overload,
      when taurine application was discontinued.

PMID- 11470257
TI  - Comparison of apomorphine, amphetamine and dizocilpine disruptions of prepulse
      inhibition in inbred and outbred mice strains.
AB  - The dopamine agonist apomorphine robustly disrupts prepulse inhibition of the
      acoustic startle response in the rat, yet published studies have not demonstrated
      a robust disruption of prepulse inhibition with apomorphine in the mouse. The aim
      of these studies was to establish the optimal prepulse conditions (using
      manipulations to prepulse intensity and inter-stimulus interval) and mouse
      strain(s) for testing apomorphine, and also the prepulse inhibition disrupting
      drugs amphetamine, and dizocilpine (MK-801). The effects of these drugs on
      startle response and prepulse inhibition were tested in outbred CD-1 and Swiss
      Webster (CFW) strains, and the inbred C57BL/6, 129X1/SvJ, and A/J strains. There
      were strain differences with baseline startle and prepulse inhibition in that the
      CD-1, CFW, and C57BL/6 strains exhibited high levels of startle and prepulse
      inhibition, the 129X1/SvJ strain exhibited low levels of startle but high levels
      of prepulse inhibition, while the A/J strain exhibited low startle and no
      prepulse inhibition. Apomorphine disrupted prepulse inhibition in the CFW and
      C57BL/6 strains and the effect was only evident when using a short 30 ms inter
      stimulus interval. Amphetamine disrupted prepulse inhibition in the CFW, C57BL/6,
      and 129X1/SvJ strains, and dizocilpine disrupted prepulse inhibition in the CD-1,
      CFW, C57BL/6, and 129X1/SvJ strains. The effects of amphetamine and dizocilpine
      were independent of the inter-stimulus interval. These studies demonstrated clear
      strain differences in the startle response and prepulse inhibition, and the
      pharmacological disruptions of prepulse inhibition, and suggest that inter
      stimulus intervals less than 100 ms may be optimal for detecting the effects of
      apomorphine in mice.

PMID- 11470258
TI  - Anti-ischemic and cognition-enhancing properties of NNC-711, a gamma-aminobutyric
      acid reuptake inhibitor.
AB  - NNC-711 [1-(2-((diphenylmethylene)amino)oxy)ethyl)-1,2,4,6-tetrahydro-3
      pyridinecarboxylic acid hydrochloride], a gamma-aminobutyric acid (GABA) reuptake
      inhibitor with anticonvulsant activity, was investigated with respect to its
      cognition-enhancing and neuroprotective potency. In the rat, administration of
      NNC-711 immediately prior to training prevented amnesia for a passive avoidance
      task induced by the acetylcholine receptor antagonist scopolamine. NNC-711 was
      also effective in protecting against ischemia-induced death of CA1 pyramidal
      neurons in a model of bilateral common carotid artery occlusion in the gerbil. In
      addition to a neuroprotective activity, NNC-711 exhibited significant cognition
      enhancing actions. Daily administration of NNC-711, immediately prior to a
      spatial learning task, significantly reduced escape latencies in the water maze
      paradigm in both mature (postnatal day 80) and aged (28 months) rats. All of the
      above actions exhibited a bell-shaped response with an optimal dose of 0.5-1.0
      mg/kg. These investigations with NNC-711 and previous clinical observations on
      the structurally related anticonvulsant tiagabine confirm the potential of GABA
      reuptake inhibitors as anti-amnesia and cognition-enhancing agents.

PMID- 11470259
TI  - Effects of 5-HT2 and 5-HT3 receptors on the modulation of nociceptive
      transmission in rat spinal cord according to the formalin test.
AB  - We used the formalin test to clarify the 5-hydroxytryptamine (5-HT) receptor
      subtypes involved in the modulation of spinal nociceptive transmission in rats.
      Intrathecal administration of a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n
      propylamino)-tetraline (8-OH-DPAT; 1, 10, and 30 microg), or a 5-HT1B receptor
      agonist, 1, 4-dihydro-3-(1, 2, 3, 6-tetrahydro-4-pyridinyl)-5H-pyrrol (3, 2-b)
      pyridin-5-one (CP 93129; 1 and 10 microg), produced no significant change in the
      number of flinches. A 5-HT(2) receptor agonist, (+/-)-2, 5-dimethoxy-4
      iodoamphetamine (DOI; 10, 30, and 100 microg), and a 5-HT3 receptor agonist, 2
      methyl-5-HT (100 and 300 microg), produced dose-dependent decreases in the number
      of flinches in phases 1 (1 to 6 min) and 2 (10 to 61 min) of the test. The
      antinociceptive effects of DOI and 2-methyl-5-HT were antagonized by intrathecal
      pretreatment with a 5-HT2 receptor antagonist, ketanserin, and a 5-HT3 receptor
      antagonist, 3-tropanyl-3, 5-dichlorobenzoate (MDL-72222), respectively. These
      results suggest that 5-HT2 and 5-HT3 receptors in the spinal cord mediate
      antinociception to chemical stimuli.

PMID- 11470260
TI  - The effect of adrenergic compounds on neurogenic dural vasodilatation.
AB  - The pharmacology of neurogenic trigeminovascular vasodilator responses in the
      dura mater is of interest for understanding the pathophysiology of migraine and
      to develop new therapies for this disabling common condition. Aminergic
      mechanisms have been implicated in migraine through direct study of amines in
      patients, and by inference from the pharmacology of many effective anti-migraine
      compounds, particularly preventative agents. This study used intravital
      microscopy to assess the role of aminergic transmission in neurogenic dural
      vasodilatation (NDV) by measuring directly the diameter of dural arteries in
      sodium pentobarbitone anaesthetised rats. Electrical stimulation of a closed
      cranial window produces, by local depolarisation of nerves, dural vessel dilation
      that is monitored continuously on-line using video-microscopy and a video
      dimension analyser. This dural vasodilatation was not affected by pre-treatment
      with an alpha1-adrenoceptor agonist (phenylephrine, 1 and 5 microg/kg), or
      antagonist (corynanthine, 1 and 2 mg/kg), nor by an alpha2-adrenoceptor agonist
      (UK14,304, 5 microg/kg) or antagonist (yohimbine, 1 and 3 mg/kg). Similarly, we
      saw no effect of beta-adrenoceptor blockade (propranolol, 1 and 3 mg/kg). The
      lack of an inhibitory effect of UK14,304 the model of neurogenic dural
      vasodilation contrasts with its effect in neurogenic dural plasma protein
      extravasation model. The lack of inhibition of beta-adrenoceptor antagonists in
      the neurogenic vasodilatation model contrasts with their usefulness as migraine
      prophylactics, and suggests that their mechanism of action in migraine is
      unlikely to be through sensory trigeminal fibre terminals at the neurovascular
      junction. Moreover, the data indicate that the adrenergic system does not play a
      significant role in neurogenic dural vasodilation.

PMID- 11470261
TI  - Effects of the endothelin receptor antagonist Bosentan on ischaemia/reperfusion
      injury in rat skeletal muscle.
AB  - We examined the role of endothelin in ischaemia/reperfusion injury in skeletal
      muscle, using the endothelin receptor antagonist Bosentan. In the rat hindlimb
      tourniquet ischaemia model, one hindlimb was rendered ischaemic for 2 h at 36
      degrees C, then blood flow was re-established for either 24 h to assess muscle
      survival or 1.5 h for a study of capillary perfusion. In the first set of rats,
      the gastrocnemius muscle was removed from the postischaemic limb and assessed for
      viability histochemically using the nitro blue tetrazolium stain. Tissue water
      content (a measure of oedema) and myeloperoxidase activity (a measure of
      neutrophil accumulation) were also assessed in the ischaemic muscle, the
      contralateral non-ischaemic muscle and the lungs. In the second set of rats, the
      hind limb was infused with India ink after 2-h ischaemia and 1.5-h reperfusion
      and the muscle was harvested, fixed and cleared. In control rats, muscle
      viability was 17+/-2% (S.E.M.). In rats treated with Bosentan (10 mg/kg, i.p.) 30
      min before release of the tourniquet, muscle viability (48+/-7%) was
      significantly increased compared to the control group (P<0.01). Bosentan
      treatment had no significant effect on tissue water content or myeloperoxidase
      activity in the ischaemic muscle, the contralateral non-ischaemic muscle or the
      lung. Immunoreactive endothelin levels in serum increased to a peak at 90 min of
      reperfusion and returned to control levels by 24-h reperfusion. India ink studies
      demonstrated a significantly increased functional capillary density in
      postischaemic Bosentan-treated muscles compared with postischaemic control
      muscles (P<0.05). These results suggest that endothelin plays an important role
      in the necrosis which results from a period of ischaemia and reperfusion in
      skeletal muscle, by mediating a decrease in postischaemic microvascular
      perfusion.

PMID- 11470262
TI  - The role of nitric oxide in the gastric acid secretion induced by ischemia
      reperfusion in the pylorus-ligated rat.
AB  - In a rat model of the ischemia-reperfusion with pylorus ligation, gastric ulcer
      was formed, although gastric acid secretion was reduced. When the
      polymorphonuclear leukocytes were inactivated in advance, gastric ulcer was not
      formed, but acid secretion was increased, indicating that gastric acid is not a
      cause of the ulcer formation in this model. The mechanism of gastric acid
      suppression accompanied by ischemia-reperfusion was examined in relation to the
      role of oxygen-free radicals in this rat model. Prior administration of
      superoxide dismutase did not modulate acid secretion, but N-nitro-L-arginine
      methyl ester (L-NAME) increased acid secretion. The action of L-NAME was
      antagonized specifically by L-arginine, but not by D-arginine. S-nitroso-N
      acetylpenicillamine did not inhibit basal acid secretion but antagonized the
      action of L-NAME. Aminoguanidine increased significantly the gastric acid output
      that was suppressed by ischemia-reperfusion. When polymorphonuclear leukocytes
      were inactivated by treatment with their antibody, the gastric acid output
      recovered to the level in the pylorus-ligated rat without ischemia-reperfusion.
      These results suggested that nitric oxide (NO) produced by the infiltrated
      polymorphonuclear leukocytes plays an important role in the suppression of acid
      secretion induced by ischemia-reperfusion.

PMID- 11470263
TI  - Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats.
AB  - Studies were performed on the mechanisms of the protective effects of free
      radical scavengers against gentamicin-mediated nephropathy. Administration of
      gentamicin, 100 mg/kg s.c., for 5 days to rats induced marked renal failure,
      characterised by a significantly decreased creatinine clearance and increased
      blood creatinine levels, fractional excretion of sodium Na(+), lithium Li(+),
      urine gamma glutamyl transferase and daily urine volume. A significant increase
      in kidney myeloperoxidase activity and lipid peroxidation was observed in
      gentamicin-treated rats. Immunohistochemical localisation demonstrated
      nitrotyrosine formation and poly(ADP-ribose)synthase activation in the proximal
      tubule from gentamicin-treated rats. Renal histology examination confirmed the
      tubular necrosis. N-acetylcysteine (10 mg/kg i.p. for 5 days) caused
      normalisation of the above biochemical parameters. In addition, N-acetylcysteine
      treatment significantly prevents the gentamicin-induced tubular necrosis. These
      results suggest that (1) N-acetylcysteine has protective effects on gentamicin
      mediated nephropathy, and (2) the mechanisms of the protective effects can be, at
      least in part, related to interference with peroxynitrite-related pathways.

PMID- 11470264
TI  - Isotope effects in the study of enzymatic phosphoryl transfer reactions.
AB  - Protein-tyrosine phosphatases and serine/threonine protein phosphatases utilize
      very different catalytic machinery to catalyze phosphoryl transfer reactions.
      Tyrosine is a better leaving group than serine or threonine, having a pK(a) more
      than three units lower. Has the difference in the catalytic machinery used by
      these enzyme families evolved as a result of the difference in the lability of
      their substrates? Are the transition states for phosphoryl transfer similar for
      the two classes of enzymes? This review summarizes what has been learned from
      kinetic isotope effects about the nature of enzymatic phosphoryl transfer, and
      how the enzymatic mechanisms compare to uncatalyzed phosphoryl transfer
      reactions.

PMID- 11470265
TI  - Does myoglobin protect Trypanosoma cruzi from the antiparasitic effects of nitric
      oxide?.
AB  - The hemoflagellate protozoan parasite Trypanosoma cruzi is the causative agent of
      Chagas disease, a progressive fatal cardiomyopathy widespread in South and
      Central America. Here, we postulate that the preferential colonization of
      cardiomyocytes by T. cruzi may reflect the role of myoglobin (Mb) as a nitric
      oxide (NO) scavenger, protecting the parasite from the trypanocidal effects of
      NO. The proposal of this novel function of Mb is based on knowledge that ferrous
      oxygenated Mb reacts rapidly and irreversibly with NO yielding nitrate and ferric
      oxidized Mb, which is reduced back to the physiologically active form by an
      intracellular reductase. The postulated protective role of Mb on the viability of
      T. cruzi is reminiscent of that postulated for hemoglobin in protecting
      intraerythrocytic Plasmodia from the parasiticidal effect of NO.

PMID- 11470266
TI  - Oligosaccharyltransferase is highly specific for the hydroxy amino acid in Asn
      Xaa-Thr/Ser.
AB  - Pig liver oligosaccharyltransferase (OST), which is involved in the en bloc
      transfer of the Dol-PP-linked GlcNAc(2)-Man(9)-Glc(3) precursor on to asparagine
      residues in the Asn-Xaa-Thr/Ser sequence, is highly stereospecific for the
      conformation of the 3-carbon atom in the hydroxy amino acid. Moreover,
      substitution of the hydroxy group by either SH as in cysteine, or NH(2) as in
      beta,gamma-diamino-butanoic acid as reported previously [Bause, E. et al.,
      Biochem. J. 312 (1995) 979-985], followed by the determination of the pH optimum
      for enzymatic activity, indicates that neither a negative nor a positive charge
      in the hydroxy amino acid position is tolerated by the enzyme. Binding of the
      threonine beta-methyl group by OST is also specific, with serine, L-threo-beta
      hydroxynorvaline and L-beta-hydroxynorleucine containing tripeptides all bound
      much less efficiently than the threonine peptide itself. The data are interpreted
      in terms of a highly stereospecific hydrophobic binding pocket for the threonine
      CH(3)-CH(OH) group.

PMID- 11470267
TI  - Domain II of m-calpain is a Ca(2+)-dependent cysteine protease.
AB  - Calpain, a Ca(2+)-dependent cytosolic cysteine protease, proteolytically
      modulates specific substrates involved in Ca(2+)-mediated intracellular events,
      such as signal transduction, cell cycle, differentiation, and apoptosis. The 3D
      structure of m-calpain, in the absence of Ca(2+), revealed that the two
      subdomains (domains IIa and IIb) of the protease domain (II) have an 'open'
      conformation, probably due to interactions with other domains. Although the
      presence of an EF-hand structure was once predicted in the protease domain, no
      explicit Ca(2+)-binding structure was identified in the 3D structure. Therefore,
      it is predicted that if the protease domain is excised from the calpain molecule,
      it will have a Ca(2+)-independent protease activity. In this study, we have
      characterized a truncated human m-calpain that consists of only the protease
      domain. Unexpectedly, the proteolytic activity was Ca(2+)-dependent, very weak,
      and not effectively inhibited by calpastatin, a calpain inhibitor. Ca(2+)
      dependent modification of the protease domain by the cysteine protease inhibitor,
      E-64c, was clearly observed as a SDS-PAGE migration change, indicating that the
      conformational changes of this domain are a result of Ca(2+) binding. These
      results suggest that the Ca(2+) binding to domain II, as well as to domains III,
      IV, and VI, is critical in the process of complete activation of calpain.

PMID- 11470268
TI  - Use of amphipathic polymers to deliver a membrane protein to lipid bilayers.
AB  - Data are presented which suggest that a class of amphiphilic polymers known as
      'amphipols' may serve as a vehicle for delivering complex integral membrane
      proteins into membranes. The integral membrane protein diacylglycerol kinase
      (DAGK) was maintained in soluble form by either of two different amphipols. Small
      aliquots of these solutions were added to pre-formed lipid vesicles and the
      appearance of DAGK catalytic activity was monitored as an indicator of the
      progress of productive protein insertion into the bilayers. For one of the two
      amphipols tested, DAGK was observed to productively transfer from its amphipol
      complex into vesicles with moderate efficiency. Results were not completely clear
      for the other amphipol.

PMID- 11470269
TI  - Identification and tissue distribution of novel KET/p63 splice variants.
AB  - The human p53 protein family comprises three members - p53, p63 and p73. Whereas
      only one p53 variant is known multiple isoforms of p63 and p73 have been
      described. Depending on the isoform p63 influences p53-responsive genes in a p53
      like or -distinct manner. We have cloned multiple splice variants of keratinocyte
      transcription factor (KET), the rat ortholog of human p63. Several tissue
      specific variations of exon 1 resulting in different amino-terminal ends were
      identified. Transactivation properties of the splice variants inversely
      correlated with the length of the N-termini as determined by activation of the
      p53-responsive p21 promotor. Multiple KET isoforms are colocalized in different
      rat tissues. The amino-terminal truncated form DeltaNKETalpha is expressed in
      epithelial tissues, while expression of the most p53-like KET isotype TAKETgamma
      was detected in skeletal muscle. Expression of a major KET variant appears to be
      a cell-type specific rather than a differentiation specific phenomenon.

PMID- 11470270
TI  - Translational selection shapes codon usage in the GC-rich genome of Chlamydomonas
      reinhardtii.
AB  - In unicellular species codon usage is determined by mutational biases and natural
      selection. Among prokaryotes, the influence of these factors is different if the
      genome is skewed towards AT or GC, since in AT-rich organisms translational
      selection is absent. On the other hand, in AT-rich unicellular eukaryotes the two
      factors are present. In order to understand if GC-rich genomes display a similar
      behavior, the case of Chlamydomonas reinhardtii was studied. Since we found that
      translational selection strongly influences codon usage in this species, we
      conclude that there is not a common pattern among unicellular organisms.

PMID- 11470271
TI  - Proper receptor signalling in a mutant catfish gonadotropin-releasing hormone
      receptor lacking the highly conserved Asp(90) residue.
AB  - The negatively charged side chain of an Asp residue in transmembrane domain 2 is
      likely to play an important role in receptor signalling since it is highly
      conserved in the whole family of G protein-coupled receptors, except in mammalian
      gonadotropin-releasing hormone (GnRH) receptors. In this paper we show that the
      conserved Asp(90) of the catfish GnRH receptor can be substituted by a neutral
      Asn(90) without abolishing receptor signalling if another negatively charged
      Glu(93) is introduced in a proximal region of the receptor interior, thereby
      mimicking the Glu(90)-Lys(121) salt bridge of mammalian GnRH receptors.

PMID- 11470272
TI  - Splice donor site mutation in the lysosomal neuraminidase gene causing exon
      skipping and complete loss of enzyme activity in a sialidosis patient.
AB  - Sialidosis is a lysosomal storage disease caused by the deficiency of alpha-N
      acetylneuraminidase (NEU1; sialidase), the key enzyme for the intralysosomal
      catabolism of sialylated glycoconjugates. We have identified a homozygous
      transversion in the last intron (IVSE +1 G>C) in neu1 of a sialidosis patient.
      Sequencing of the truncated cDNA revealed an alternatively spliced neu1
      transcript which lacks the complete sequence of exon 5. Skipping of exon 5 leads
      to a frameshift and results in a premature termination codon. This is the first
      description of an intronic point mutation causing a complete deficiency of the
      lysosomal neuraminidase activity.

PMID- 11470273
TI  - Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene
      via binding to IL-18.
AB  - To understand modulation of a novel immune-related cytokine, interleukin-18, by
      human papillomavirus type (HPV) 16 oncogenes, HaCaT, normal keratinocyte cell
      line, and C-33A, HPV-negative cervical cancer cell line, were prepared to
      establish stable cell lines expressing E6, E6 mutant (E6m), E6E7, or E7
      constitutively. Expressions of various HPV oncogene transcripts were identified
      by RT-PCR. Expression of HPV oncogene E6 was reversely correlated to the
      expression of interleukin-18, a novel pro-inflammatory cytokine. The expression
      of E6 in C-33A, independent of E6 splicing, resulted in decreased IL-18
      expression and that of IL-18 was also significantly reduced in HaCaT cells
      expressing E6. The level of p53 was reduced in C-33A cells expressing E6 whereas
      not altered in HaCaT cells expressing E6, suggesting that E6 downregulated IL-18
      expression via an independent pathway of p53 degradation in HaCaT cells which
      have a mutated p53 form. However, E7 did not affect IL-18 expression
      significantly in both C-33A and HaCaT cells. Cotransfection experiments showed
      that E6 oncogene did not inhibit the activities of IL-18 promoter P1 and P2,
      suggesting that E6 oncogene indirectly inhibited IL-18 expression. Taken
      together, E6, E6m and E6/E7 inhibited IL-18 expression with some variation,
      assuming that cells expressing E6 oncogene can evade immune surveillance by
      downregulating the expression of immune stimulating cytokine gene, IL-18, and
      inhibiting the cascade of downstream effects that follow activation of the IL-18
      receptor.

PMID- 11470274
TI  - Optimization of the antimicrobial activity of magainin peptides by modification
      of charge.
AB  - Investigation of magainin II amide analogs with cationic charges ranging between
      +3 and +7 showed that enhancement of the peptide charge up to a threshold value
      of +5 and conservation of appropriate hydrophobic properties optimized the
      antimicrobial activity and selectivity. High selectivity was the result of both
      enhanced antimicrobial and reduced hemolytic activity. Charge increase beyond +5
      with retention of other structural motifs led to a dramatic increase of hemolytic
      activity and loss of antimicrobial selectivity. Selectivity could be restored by
      reduction of the hydrophobicity of the hydrophobic helix surface (H(hd)), a
      structural parameter not previously considered to modulate activity. Dye release
      experiments with lipid vesicles revealed that the potential of peptide charge to
      modulate membrane activity is limited: on highly negatively charged 1-palmitoyl-2
      oleoylphosphatidyl-DL-glycerol bilayers, reinforcement of electrostatic
      interactions had an activity-reducing effect. On neutral 1-palmitoyl-2
      oleoylphosphatidylcholine bilayers, the high activity was determined by H(hd).
      H(hd) values above a certain threshold led to effective permeabilization of all
      lipid systems and even compensated for the activity-reducing effect of charge
      increase on highly negatively charged membranes.

PMID- 11470275
TI  - Distribution of blue-sensitive photoreceptors in amphibian retinas.
AB  - Previously, we reported that an opsin (Rc-MS) belonging to the SWS2 group opsins
      is expressed in bullfrog green rods [Hisatomi, O. et al., FEBS Lett., 1999, 447,
      44-48]. An anti-Rc-MS antiserum recognized the cones of the Japanese common newt,
      Cynops pyrrhogaster, which has no green rods. We isolated a cDNA encoding an SWS2
      group opsin (Cp-SWS2) from this newt and found that Cp-SWS2 is expressed in a
      small population of the cones. Our results suggest that SWS2 opsins can be
      expressed in either green rods or cones of caudata. It seems reasonable to
      suppose that green rods arose before amphibia were divided into caudata and
      anura.

PMID- 11470276
TI  - Agonist-induced internalization and mitogen-activated protein kinase activation
      of the human prostaglandin EP4 receptor.
AB  - We examined the pathway of prostaglandin E(2) (PGE(2))-induced internalization of
      the prostaglandin EP4 receptor in HEK 293 cells. Co-expression of dominant
      negative beta-arrestin (319-418) or dynamin I (K44A) with the EP4 receptor
      reduced internalization. The activated receptor co-localized with GFP-arrestin 2
      and GFP-arrestin 3, confirming the requirement for beta-arrestins in
      internalization. Inhibition of clathrin-coated vesicle-mediated internalization
      resulted in inhibition of sequestration, whereas inhibition of caveola-mediated
      internalization had no effect. PGE(2) stimulation of the EP4 receptor resulted in
      rapid mitogen-activated protein (MAP) kinase activation. Examination of an
      internalization-resistant mutant and co-expression of mutant accessory proteins
      with EP4 revealed that MAP kinase activation proceeds independently of
      internalization.

PMID- 11470277
TI  - Glu-256 is a main structural determinant for oligomerisation of human arginase I.
AB  - One determinant that could play a role in the quaternary structure of human
      arginase is the pair of salt links between the strictly conserved residues R255
      from one monomer and E256 from every adjacent subunit. In this work, the ionic
      interaction between monomers was disrupted by expressing a human arginase where
      Glu-256 had been substituted by Gln. Biochemical analyses of the mutant protein
      showed that: (i) it shares the wild-type kinetic parameters of the arginine
      substrate; (ii) E256Q arginase behaves as a monomer by gel filtration; (iii) it
      is drastically inactivated by dialysis in the presence of EDTA, an inhibitory
      effect which is reversed by addition of Mn(2+); and (iv) the mutant enzyme loses
      thermal stability. The lack of oligomerisation for E256Q arginase and the
      conservation of E256 throughout evolution of the protein family suggest that this
      residue is involved in the quaternary structure of arginases.

PMID- 11470278
TI  - Functional roles of the tyrosine within the NP(X)(n)Y motif and the cysteines in
      the C-terminal juxtamembrane region of the CB2 cannabinoid receptor.
AB  - In G protein-coupled receptors, a NP(X)(n)Y motif in the seventh transmembrane
      domain and cysteine residues in the C-terminal juxtamembrane region are
      conserved. In the current study, the roles of Y299 within the NPVIY motif and
      C313 and C320 in the C-terminal juxtamembrane region of the human CB2 cannabinoid
      receptor were investigated by site-directed mutagenesis. Replacing Y299 with
      alanine resulted in a complete loss of ligand binding and a severe impairment of
      cannabinoid-induced inhibition of forskolin-stimulated cAMP accumulation. The
      C313A and C320A mutations markedly reduced functional coupling to adenylate
      cyclase, but had no effect on ligand binding and agonist-induced receptor
      desensitization.

PMID- 11470279
TI  - Structural analysis of emerin, an inner nuclear membrane protein mutated in X
      linked Emery-Dreifuss muscular dystrophy.
AB  - Like Duchenne and Becker muscular dystrophies, Emery-Dreifuss muscular dystrophy
      (EDMD) is characterized by myopathic and cardiomyopathic abnormalities. EDMD has
      the particularity of being linked to mutations in nuclear proteins. The X-linked
      form of EDMD is caused by mutations in the emerin gene, whereas autosomal
      dominant EDMD is caused by mutations in the lamin A/C gene. Emerin colocalizes
      with lamin A/C in interphase cells, and binds in vitro to lamin A/C. Recent work
      suggests that lamin A/C might serve as a receptor for emerin. We have undertaken
      a structural analysis of emerin, and in particular of its N-terminal domain,
      which is comprised in the emerin segment critical for binding to lamin A/C. We
      show that region 2-54 of emerin adopts the LEM fold. This fold was originally
      described in the two N-terminal domains of another inner nuclear membrane protein
      called lamina-associated protein 2 (LAP2). The existence of a conserved solvent
      exposed surface on the LEM domains of LAP2 and emerin is discussed, as well as
      the nature of a possible common target.

PMID- 11470281
TI  - Detection of multiple proteins in an antibody-based protein microarray system.
AB  - A new antibody-based protein array assay is described. This assay combines the
      advantages of the specificity of enzyme-linked immunosorbent assays (ELISA),
      sensitivity of enhanced chemiluminescence (ECL) and high-throughput of microspot.
      In this system, the capture proteins, either antibodies or antigens are spotted
      onto membranes in an array format. Biological samples are then incubated with
      membranes. After antigens or antibodies in the samples bind to their
      corresponding targets and unbound proteins are washed away, the membranes are
      exposed to Horseradish Peroxidase (HRP)-conjugated antibody(ies). The signals are
      finally visualized with ECL system. Experiments demonstrate that multiple
      cytokines and antibodies can be simultaneously detected using this new approach.
      The procedure is so simple that no sophisticated equipment is required. The
      concept should be able to be extended to develop a high-throughput protein array
      system. Future applications of this new approach include direct protein
      expression profiling, immunological disease diagnostics and discovery of new
      biomarkers.

PMID- 11470282
TI  - The detection of the HLA-B27 antigen by immunomagnetic separation and enzyme
      linked immunosorbent assay-comparison with a flow cytometric procedure.
AB  - The HLA-B27 antigen is an important genetic marker in ankylosing spondylitis
      (AS). Methods for the detection of B27 include the microlymphocytotoxicity test
      and, more recently, flowcytometry (FC). Here, we describe a new method, IMS
      ELISA, for measuring the B27-antigen. It combines immunomagnetic separation
      (IMS), to obtain B27-positive cells from whole blood samples, with an enzyme
      linked immunosorbent assay (ELISA) as a read-out. IMS-ELISA was tested on 367
      samples obtained from five different hospitals in Taiwan. The sensitivity,
      specificity and accuracy of the method were compared with FC. Any conflicting
      data between IMS-ELISA and FC was confirmed by HLA-DNA typing via PCR-SSP
      (polymerase chain reaction-sequence specific primers). Overall, the results for
      sensitivity, specificity and accuracy obtained by IMS-ELISA and FC did not show
      any significant difference (p>0.05). However, when considering laboratory time,
      cost, ease of operation and the screening of large samples for HLA-B27, the IMS
      ELISA was superior to the FC method. We conclude that IMS-ELISA may be used as a
      fast screening method for HLA B27 detection.

PMID- 11470283
TI  - Inhibitory effects of T-cell stimulation and co-stimulation observed at high
      concentrations of plate-bound antibodies.
AB  - Plate-bound monoclonal antibodies (mAb) are often used as a way of stimulating
      lymphocytes in vitro. Our observations show that the concentrations of mAb used
      in functional assays in vitro must be carefully assessed before conclusions are
      drawn about lymphocyte activation or co-activation.

PMID- 11470284
TI  - Use of overlapping peptide mixtures as antigens for cytokine flow cytometry.
AB  - Intracellular cytokine staining and flow cytometry can be used to measure T-cell
      responses to defined antigens. Although CD8+ T-cell responses to soluble proteins
      are inefficiently detected by this approach, peptides can be used as antigens.
      Using overlapping peptides spanning an entire protein sequence, CD8+ T-cell
      responses can be detected to multiple epitopes, regardless of HLA type. In this
      study, overlapping peptide mixes of various lengths were compared and 15 amino
      acid peptides with 11 amino acid overlaps were found to stimulate both CD4+ and
      CD8+ T-cell responses. Such peptide mixes stimulated CD4+ T-cell responses
      equivalent to those observed with whole recombinant protein, while simultaneously
      stimulating CD8+ T-cell responses much higher than those observed with whole
      protein. Although 8-12 amino acid peptides produced the highest level of CD8+ T
      cell responses, 15 amino acid peptides were still very effective. Peptides that
      were 20 amino acids in length, however, did not stimulate strong CD8+ T-cell
      responses at the same peptide dose. The cytokine responses to individual epitopes
      added up approximately to the response to the entire mix, demonstrating that
      large mixes can detect responses in a quantitative fashion. Unlike whole protein
      antigens, peptide mixes were effective at stimulating responses in both
      cryopreserved PBMC and blood stored for 24 h at room temperature. Thus,
      overlapping 15 amino acid peptide mixes may facilitate the analysis of antigen
      specific CD4+ and CD8+ T-cell responses by cytokine flow cytometry, using
      clinical specimens that include shipped blood or cryopreserved PBMC.

PMID- 11470285
TI  - Identification of human serum interferants in the recombinant P-selectin
      glycoprotein ligand-1 clinical ELISA using MALDI MS and RP-HPLC.
AB  - A colorimetric enzyme-linked immunosorbent assay (ELISA) was developed to detect
      circulating levels of rPSGL to permit pharmacokinetic analysis of clinical
      samples. The ELISA is an asymmetric sandwich utilizing a monoclonal antibody
      pair. Initial validation studies indicated that 57% of normal individuals scored
      above the limit of detection of the assay. Specificity experiments indicated that
      the signal was not due to circulating endogenous P-selectin glycoprotein ligand-1
      (PSGL-1). Using matrix-assisted laser desorption ionization mass spectrometry
      (MALDI MS) and sampling within the individual microplate wells, the interferant
      was detected in the vicinity of 6.6 kDa in lipemic and normal human sera, but not
      delipidized sera. These results were consistent with the ELISA data where 97.5%
      of known lipemic, 57% of normal, and 0% of delipidized sera scored above
      detectable limits in the ELISA. Preparative isolations of the 6.6 kDa species
      were performed using reversed-phase high performance liquid chromatography (RP
      HPLC) with UV and MS detection. Edman N-terminal sequencing identified the 6.6
      kDa unknown as Apolipoprotein C-I. Additional apolipoproteins were found by MALDI
      and RP-HPLC. Digestion of sera with liposome lipase and extraction of sera with
      anti-apolipoprotein C-I, C-II, and C-III antibody beads significantly reduced the
      ELISA interference. These experiments combined with the MALDI detection of
      phosphatidylcholine-type lipids from NHS eluate suggested that lipoprotein
      particles or remnants were causing the interference. A method combining Triton-X
      100 with sonication was developed to overcome this interference without altering
      rPSGL recovery in the ELISA.

PMID- 11470286
TI  - Use of fluorescence polarization to monitor MHC-peptide interactions in solution.
AB  - We describe here fluorescence polarization-based methods to investigate class I
      MHC-peptide interactions in solution. Fluorescein-labelled peptides were used to
      determine MHC/peptide complex association and dissociation constants as well as
      the equilibrium binding constant (KD). Furthermore, we developed a competition
      assay for the determination of IC50 values of nonlabelled compounds. Both kinetic
      and equilibrium parameters are of prime importance for the development of
      immunomodulating compounds. The assays described here show a good reproducibility
      and require only picomolar amounts of labelled tracers. A high ratio between the
      experimental values obtained for bound and free labelled ligand as well as a low
      standard deviation, permits the detection of class I MHC ligands with low
      affinity. Fluorescence polarization allows the direct measurement of the ratio
      between free and bound labelled ligand in solution without any separation step.
      Thus, in combination with microtiter-plates, the time for analysis is
      significantly decreased to 10 s per sample. Our assays represent versatile tools
      for characterizing the binding of single ligands as well as for rapid screening
      of large numbers of compounds.

PMID- 11470287
TI  - Identification of a soluble OX40 isoform: development of a specific and
      quantitative immunoassay.
AB  - OX40 (CD134) is a member of the TNF receptor family and is expressed selectively
      on activated T lymphocytes. Through interactions with OX40 ligand, OX40 delivers
      potent costimulatory signals to T cells. Here, we describe a sandwich ELISA
      method for the detection and quantification of OX40 using the monoclonal anti
      OX40 antibodies ACT35 and L106 as capture and detecting antibodies, respectively.
      With this ELISA, the existence of naturally occurring soluble forms of OX40
      (sOX40) could be demonstrated for the first time. Soluble OX40 is detectable in
      serum of subpopulations of healthy donors and patients with autoimmune disease
      and cancer. Among the five diseases that were investigated, chronic lymphocytic
      leukemia was identified as the one with the highest frequency of sOX40-positive
      sera and with the highest mean sOX40 serum concentration. The stability of sOX40
      is not affected by repeated freeze/thaw cycles nor by prolonged storage at -20
      degrees C, allowing studies on the potential diagnostic significance of sOX40
      using existing banks of sera.

PMID- 11470288
TI  - A novel system for investigating the ability of smooth muscle cells and
      fibroblasts to regulate adhesion of flowing leukocytes to endothelial cells.
AB  - Stromal cells may contribute to the inflammatory processes which lead to the
      recruitment of circulating leukocytes. Here, we describe a multicellular model in
      which chosen cellular elements of tissue can be cocultured with endothelial cells
      (EC). Cocultures can be incorporated into a novel parallel plate flow chamber to
      determine if stromal cells influence the patterns of leukocyte adhesion to the
      EC. As an example relevant to the pathology of atherosclerosis, EC were cultured
      with arterial smooth muscle cells (SMC) of the 'secretory' phenotype. EC and
      secretory SMC were cultured on the opposite faces of commercially available
      porous polyethylene terepthalate (PET) culture inserts, which fitted into a
      parallel plate flow chamber. Binding of flowing purified lymphocytes, labelled
      with the fluorochrome calcein-AM, to cocultured EC was assessed by fluorescence
      microscopy. Lymphocyte adhesion was negligible on unstimulated EC cultured alone
      or cocultured with SMC. However, when tumour necrosis factor-alpha (TNF) was
      added to cocultures, the EC supported greatly increased levels of lymphocyte
      adhesion compared to TNF-treated EC cultured alone. Additionally, cocultured EC
      responded to TNF at concentrations far below those at which EC cultured alone
      responded. This priming was specific in that skin fibroblasts cocultured with EC
      did not modify lymphocyte adhesion induced by TNF. Thus, we have developed a
      coculture model to determine the ability of tissue stromal cells to modify
      leukocyte recruitment. This may have wide applications in the study of the
      cellular pathology of inflammation by allowing the contribution of the local
      microenvironment to be assessed.

PMID- 11470289
TI  - Extraction of human Langerhans cells: a method for isolation of epidermis
      resident dendritic cells.
AB  - Langerhans cells (LCs) are immature dendritic cells in the epidermis that play a
      central role in T-lymphocyte mediated skin immunity. Upon activation with
      antigenic stimuli, they differentiate drastically into mature dendritic cells
      while migrating from the epidermis to regional lymph nodes. Thus, in order to
      study biological details of immature LCs, it is crucial to isolate epidermis
      resident, immature LCs without dermal dendritic cell contamination. Methods for
      extracting LCs from human skin as well as in vitro derivation of LC-like cells
      from hematopoietic progenitor cells have been described previously, but the cell
      preparations can potentially contain a significant number of dendritic cells that
      are not identical to epidermal LCs. Here, we describe a technique by which purely
      epidermis-resident LCs are extracted from human skin. Following digestion of
      human skin with dispase, the epidermis was separated mechanically without any
      attached dermal component. The trypsinized epidermal cells were then fractionated
      by centrifugation with a discontinuous density gradient composed of bovine
      albumin and sodium metrizoate. The LC-enriched preparation thus obtained
      contained 80% to >90% CD1a+, E-cadherin+ cells that expressed Birbeck granules
      and the Lag protein. Consistent with their being at an immature stage, the
      freshly isolated LCs lacked the expression of CD83, a marker for mature dendritic
      cells. The purified LCs were able to activate allogeneic T cells, indicating that
      the cells retained T-cell stimulation ability even after extraction. Thus, the
      present work offers an opportunity for precise in vitro studies of epidermal LCs.

PMID- 11470290
TI  - CD19+ B lymphocytes are the major source of human antibody-secreting hybridomas
      generated by electrofusion.
AB  - Human monoclonal antibodies may be generated by electrofusion of human B
      lymphocytes with a human/mouse heteromyeloma line. In addition to a fusion
      protocol optimised for the fusion partners, the activation of B lymphocytes is
      crucial for fusion and hybrid efficiency. In this study, we initially treated
      peripheral blood mononuclear cells (PBMC) from normal blood donors with a large
      panel of known stimulants and determined the yield of human antibody-secreting
      hybridomas after electrofusion with the heteromyeloma cell line H73C11; 3- to 5
      day incubation with phytohaemagglutinin L (PHA-L) resulted in the highest number
      of secreting hybrids. In a second set of experiments, PBMC were depleted from
      various cell populations, including CD14+ monocytes, CD8+ T lymphocytes, and CD2+
      T cells, respectively. Undepleted PBMC stimulated with PHA-L were shown to give
      rise to the highest number of secreting hybridomas when subjected to
      electrofusion, whereas depletion of CD2+ T lymphocytes greatly reduced the yield.
      In a final set of experiments, CD19+ B lymphocytes were identified as the major
      source of secreting hybridomas. For optimal fusion efficiency, CD19+ B cells were
      shown to require direct physical contact with other cell populations, most
      probably T lymphocytes, during the stimulation process. Our data highlight the
      importance of an adequate stimulation prior to electrofusion and may be helpful
      to further facilitate the development of human monoclonal antibodies.

PMID- 11470291
TI  - High-yield expression of the recombinant, atrazine-specific Fab fragment K411B by
      the methylotrophic yeast Pichia pastoris.
AB  - In this report, we describe the high-yield secretory expression ( approximately
      40 mg x l(-1)) of pure, atrazine-specific Fab fragments (K411B) from Pichia
      pastoris that was achieved by co-integration of the genes encoding the heavy and
      light chains (both under the control of the alcohol oxidase promoter) into the
      genome of the yeast cells. Antibody-expressing clones were selected by SDS-PAGE
      and ELISA and fed-batch fermentations were carried out in a 5-l scale. Both
      chains of the Fab were successfully expressed upon methanol induction and almost
      no other proteins were secreted into the media. Approximately 30% of the two
      chains formed the active Fab fragment containing the intermolecular disulphide
      bond, as determined by Western blot analysis under non-reducing conditions. Crude
      culture supernatant was used to study the binding properties of the Fab fragment
      toward different s-triazines by means of competitive ELISA: the IC50 value for
      the detection of atrazine was determined from the standard curve as 3 microg x l(
      1), which is one magnitude higher than the value obtained with the parental mAb
      K4E7 but equals that obtained when the same Fab fragment was expressed in
      Escherichia coli cells. In addition, the cross-reactivity pattern of the Fab from
      Pichia is comparable to that of E. coli and to the parental mAb K4E7.

PMID- 11470292
TI  - RANTES and MIP-1beta mRNA expression in human peripheral blood mononuclear cells:
      transcript quantification using NASBA technology.
AB  - The importance of chemokines in the immune response, as well as in a range of
      specific disease states, is becoming increasingly apparent. The role of CC- (or
      beta-) chemokines and their receptors in the pathology and mechanisms of HIV-1
      infection has served to intensify interest in these factors. Although the
      functionality of these factors resides in their protein forms, assays for the
      detection and quantification of these protein factors in clinical samples are not
      readily available. Consequently, we designed NASBA-based assays for the
      quantification of the mRNA encoding two members of the CC-chemokine family:
      RANTES and MIP-1beta. The NASBA-based assays are extremely sensitive, accurate,
      and reproducible across a dynamic range of at least four orders of magnitude.
      Inter-assay performance is comparable to intra-assay performance. We applied
      these methods to the analysis of normal human PBMC and PBMC from HIV-1 infected
      individuals. Although MIP-1beta mRNA levels are higher than RANTES levels in both
      populations, RANTES levels in HIV-1+ patients are higher than in normal
      individuals. The utility of these assays in longitudinal studies of specific
      subpopulations of cells, as well as their potential use in clinical diagnostics,
      is discussed.

PMID- 11470293
TI  - Design of cassette vectors permitting cloning of all types of human TCR variable
      alpha and beta regions.
AB  - T cell clones are an irreplaceable asset for the study of immune responses
      relevant to human pathologies. Such cells, however, cannot always be maintained
      in long-term culture. In order to reconstitute functional human T cell receptors
      (TCRs) into stable and fast growing hybridoma T cells, we developed a general
      approach based on a versatile cassette system, which allows cloning of all types
      of human T cell receptor variable alpha and beta region genes fused to murine
      constant regions. These chimeric constructs are easily excised and transferred
      into expression vectors that can be used to transfect a human CD4-expressing
      murine T cell hybridoma recipient. The resulting transfectants are highly stable
      both in terms of T cell receptor-CD3 expression and IL-2 response to the specific
      antigenic stimulus. Using these cassette vectors, we reconstituted the original
      HLA-restricted antigen specificity for two human T cell clones, one recognizing
      an immunodominant epitope of HIV-1 gp120, and the other recognizing an
      immunodominant epitope of HIV-1 reverse transcriptase. We found that the
      reconstituted hybridomas maintain the ability of the original T cell clones to
      recognize the appropriate epitope in the context of the relevant MHC either as a
      synthetic peptide or after processing. Their unlimited growth capacity makes them
      particularly suited for in vitro studies.

PMID- 11470294
TI  - In vivo and in vitro lipidation of recombinant immunogens for direct iscom
      incorporation.
AB  - We have previously reported strategies for Escherichia coli production of
      recombinant immunogens fused to hydrophobic tags to improve their capacity to be
      incorporated into an adjuvant formulation (J. Immunol. Methods 222 (1999) 171;
      238 (2000) 181). Here, we have explored the possibility to use in vivo or in
      vitro lipidation of recombinant immunogens as means to achieve iscom
      incorporation through hydrophobic interaction. For the in vivo lipidation
      strategy, a general expression vector was constructed encoding a composite tag
      consisting of a sequence (lpp) of the major lipoprotein of E. coli, fused to a
      dual affinity fusion tag to allow efficient recovery by affinity chromatography.
      Upon expression in E. coli, fatty acids would be linked to the produced gene
      products. To achieve in vitro lipidation, the target immunogen would be expressed
      in frame with an N-terminal His6-ABP affinity tag, in which the hexahistidyl tag
      was utilized to obtain lipidation via a Cu2+-chelating lipid. A 238 amino acid
      segment DeltaSAG1, from the central region of the major surface antigen SAG1 of
      Toxoplasma gondii, served as model immunogen in this study. The two generated
      fusion proteins, lpp-His6-ABP-DeltaSAG1 and His6-ABP-DeltaSAG1, both expressed at
      high levels (approximately 5 and 100 mg/l, respectively), could be recovered to
      high purity by ABP-mediated affinity chromatography, and were evaluated in iscom
      incorporation experiments. The His6-ABP-DeltaSAG1 fusion protein was associated
      to iscom matrix with pre-incorporated chelating lipid. Both fusion proteins were
      found in the iscom fractions after analytical ultracentrifugation in a sucrose
      gradient, indicating successful iscom incorporation/association. Iscom formation
      was further supported by electron microscopy analysis. In addition, these iscom
      preparations were demonstrated to induce high-titer antigen-specific antibody
      responses upon immunization of mice. For this particular target immunogen,
      DeltaSAG1, the induced antibodies demonstrated poor reactivity to the native
      antigen, although slightly better for the preparation employing the in vitro
      lipidation strategy, indicating that DeltaSAG1 was suboptimally folded or
      presented. Nevertheless, we believe that the presented strategies offer
      convenient alternative ways to achieve efficient adjuvant incorporation for
      recombinant immunogens.

PMID- 11470295
TI  - Development and optimization of cytokine ELISAs using commercial antibody pairs.
AB  - The measurement of cytokines in plasma and other fluids often requires the use of
      an enzyme-linked immunosorbant assay (ELISA). In the research environment, a
      valuable assay is one that yields reliable results in the shortest amount of time
      for the least cost. To achieve this goal, a protocol has been outlined to develop
      sandwich ELISAs for cytokines using commercial antibodies. These guidelines for
      ELISA development include selecting antibody concentrations, choosing an
      appropriate buffer, reducing plasma interference and evaluating the optimal
      length for incubation periods. In addition, the protocol for a rapid IL-6 ELISA
      is presented. This ELISA allows measurement of IL-6 in a reduced amount of time
      by raising the concentration of antibodies used and increasing the temperature
      for incubation. By following the guidelines presented, cost-effective, cytokine
      ELISAs can be developed that yield low background, detect a wide range of
      concentrations, and are suitable for use in the research setting.

PMID- 11470296
TI  - Mechanical load on the low back and shoulders during pushing and pulling of two
      wheeled waste containers compared with lifting and carrying of bags and bins.
AB  - OBJECTIVE: Compare the mechanical load on the low back and shoulders during
      pushing and pulling a two-wheeled container with the load during lifting and
      carrying the same amount of waste. BACKGROUND: Only little is known about risk
      factors and mechanical loads during push/pull operations. DESIGN: A complete 2(3)
      factor push/pull experiment. A two-wheeled container with 25 or 50 kg was pushed
      in front of and pulled behind the body by seven waste collectors. Further, the
      same subjects lifted and carried a paper bag and a dustbin both loaded with 7 and
      25 kg. METHOD: All operations were video recorded and the push/pull force was
      measured by means of a three-dimensional force transducer. Peak Motus and Watbak
      software were used for digitising and calculation of torque at L4/L5 and the
      shoulder joints and compression and shear forces at L4/L5. RESULTS: During
      pushing and pulling the compression at L4/L5 is from 605 to 1445 N. The extension
      torque at L4/L5 produced by the push/pull force is counteracted by the forward
      leaning of the upper body. The shear force is below 202 N in all situations. The
      torque at the shoulders is between 1 and 38 Nm. CONCLUSION: In the present
      experiments the torques at the low back and the shoulders are low during pushing
      and pulling. No relation exists between the size of the external force and the
      torque at the low back and the shoulder. RELEVANCE: Pushing and pulling are
      common in many workplaces and have often replaced lifting and carrying
      situations. This has emphasised the need for more knowledge of the internal
      mechanical load on the body during these activities.

PMID- 11470297
TI  - Replacing the nucleus pulposus of the intervertebral disc.
AB  - OBJECTIVE: To determine whether replacement of the nucleus with a synthetic
      material would prevent the effects of nucleus removal. DESIGN: Laboratory
      experiments on excised tissues and a finite element model. BACKGROUND: Removal of
      the nucleus from the intervertebral disc causes the inner margins of the annulus
      to bulge inwards, instead of outwards, during compression. This may cause the
      annulus to degenerate further. METHODS: Video recordings of sheep discs,
      sectioned in the sagittal plane, were obtained during compression in a materials
      testing machine; the cut face of the disc was sealed with a Perspex window.
      Experiments were repeated with the nucleus removed and then replaced by a
      synthetic implant. A finite element model of an intact disc was also used to
      investigate the effect of nucleus replacement. RESULTS: When the nucleus of
      sectioned discs was replaced with the polymer materials, the inward bulging of
      the annulus was not observed. The predictions from the finite element model of
      the intact disc were consistent with this result. CONCLUSIONS: Replacement of the
      nucleus with a synthetic material can prevent the changes in annulus behaviour
      that result from removal of the nucleus. RELEVANCE: A suitable implant to replace
      the nucleus after surgical removal may help prevent inward bulging of the inner
      layers of the annulus.

PMID- 11470298
TI  - Finite element analysis of the mechanical behavior of a scapula implanted with a
      glenoid prosthesis.
AB  - OBJECTIVE: The objective of the present study was to analyze the mechanical
      effect of some of the surgical variables encountered during shoulder arthroplasty
      using the finite element method. The effect of one eccentric load case, cement
      thickness and conformity has been investigated. DESIGN: A 3D finite element model
      of a healthy cadaveric scapula implanted with an anatomically shaped glenoid has
      been developed from computed tomography (CT) images. BACKGROUND: Glenoid
      component fixation can present the most difficult problem in total shoulder
      arthroplasty, loosening of this component remains one of the main complications.
      METHODS: The 3D finite element model was first validated by comparison with
      experimental measurements and by fitting of the mechanical properties of the
      cortical bone. Then the articular pressure location, the surface contact geometry
      and the cement thickness have been analyzed to observe their effect on stresses
      and displacements at the interfaces and within the scapular bone. RESULTS: The
      antero-posterior bending of the scapula was a notable feature and this was
      accentuated when an eccentric load was applied. The gleno-humeral contact area
      had a major role on the stress level in the supporting structures though but not
      on the global displacements. Varying the cement mantle modified stresses
      according to the load case and it essentially changed the latero-medial
      displacement of the cement relatively to the bone. CONCLUSIONS: This analysis
      provided an insight into the mechanical effects of an implanted scapula according
      to different parameters related to implantation technique. RELEVANCE: Results
      emphasized the role of some of the parameters a clinician may face. They
      demonstrated the importance of the humeral head centering in the horizontal
      plane. Conformity decreasing may involve drastic increase of stresses within
      structures and a thick cement mantle is not necessarily advantageous relatively
      to the stresses at the cement/bone interface.

PMID- 11470299
TI  - Testing apparatus and experimental procedure for position specific normalization
      of electromyographic measurements of distal upper extremity musculature.
AB  - OBJECTIVE: An apparatus and procedure are described to determine position
      specific normalization coefficients for surface EMG of upper extremity
      musculature. STUDY DESIGN: Thirty-nine subjects were tested three times.
      Repeatability of EMG measurements across test sessions was determined by
      computing intraclass correlation coefficients. Two-way analysis of variance was
      used to test upper extremity position dependent differences in EMG measurements.
      BACKGROUND: EMG measurements are susceptible to error from skin movement and
      muscle length changes, both of which may occur when upper extremity positions
      vary. Normalization of the EMG signal without consideration for such positional
      influences may lead to erroneous conclusions regarding muscle activation during
      functional tasks. METHOD: An apparatus was designed that allowed subjects to
      perform three repetitions of maximum elbow flexion, forearm pronation, wrist
      extension, and wrist flexion with the forearm in neutral and pronated positions.
      Surface EMG was sampled from eight muscles. Mean EMG on maximum voluntary
      contraction was computed, and resting EMG was subtracted to obtain EMG
      normalization coefficients. RESULTS: Upper extremity position affected the EMG
      normalization coefficient for biceps brachii, which was lower in the pronated
      position, and extensor carpi radialis, which was higher in the pronated position
      (P<0.00625). CONCLUSIONS: The apparatus accommodates various combined positions
      of the elbow, forearm and wrist. The normalization procedure is efficient for
      testing subjects who are being observed during functional tasks. Only two muscles
      were affected by upper extremity position, but group trends were not always
      consistent with individual behavior. This method would ensure the use of
      appropriate EMG normalization coefficients regardless of individual variation.
      RELEVANCE: This method is effective for normalizing EMG signals using task
      specific upper extremity positions. It may be used to test isometric exertions of
      distal upper extremity musculature for clinical and research purposes.

PMID- 11470300
TI  - Biomechanical evidence supporting a differential response to acute ACL injury.
AB  - OBJECTIVE: To describe movement patterns in people with complete anterior
      cruciate ligament rupture objectively identified as good candidates for non
      operative management of the injury. DESIGN: Involved side kinematics and kinetics
      were compared to the uninvolved side and to uninjured subjects. BACKGROUND: High
      level athletes with anterior cruciate ligament rupture and poor dynamic stability
      (non-copers) have movement alterations, including less knee flexion and a
      decreased internal knee extensor moment during loading response, that are not
      seen in those with excellent knee stability (copers). Our screening exam can
      identify people with good rehabilitation potential for non-operative management
      of anterior cruciate ligament injury (potential copers), but the movement
      strategies of these individuals are unknown. METHODS: Sagittal plane kinematics
      and kinetics during the stance phase of walking and jogging were collected from
      11 subjects who had an acute anterior cruciate ligament rupture and met the
      criteria of the screening exam, and were compared to 10 uninjured subjects, who
      we studied previously. Variables were those in which non-copers differed from
      uninjured subjects. RESULTS: The potential copers flexed their involved knee less
      than uninjured subjects and their uninvolved side during walking. Potential
      copers, compared to uninjured subjects, also had a lower vertical ground reaction
      force during loading response, a lower knee support moment, and an increased
      ankle support moment during walking. In jogging, the involved knee angle at
      initial contact was more extended compared to uninjured subjects, and the amount
      of knee flexion was less than the uninvolved side. No differences in kinetics
      were present during jogging. CONCLUSIONS: This study provides evidence that the
      potential copers identified by the screening examination have movement patterns
      that are consistent with people who have more knee stability than non-copers.
      RELEVANCE: Although potential copers have developed some characteristics of a
      successful stabilization strategy, the presence of kinematic alterations
      indicates that they may benefit from training programs designed to enhance
      dynamic knee stability.

PMID- 11470301
TI  - Inter-segment foot motion and ground reaction forces over the stance phase of
      walking.
AB  - OBJECTIVE: To compare the magnitude and patterns of motion of the rearfoot
      segment relative to the leg, forefoot segment relative to the rearfoot, height
      change in the medial longitudinal arch and ground reaction forces of normal adult
      males during the stance phase of walking. BACKGROUND: Knowledge of normal motion
      of the rearfoot and forefoot segments and of the arch during stance phase is
      important in clinical management. METHODS: Motion data were obtained from surface
      markers, and force data from a force plate, from the right limb of participants
      while walking at a self-selected pace. RESULTS: Stance phase range of motion
      across sagittal, frontal and transverse planes was 12 degrees, 4 degrees and 10
      degrees for the forefoot, compared to 22 degrees, 8 degrees and 10 degrees for
      the rearfoot. Most motion occurred at the beginning and end of stance phase when
      support was via only the rearfoot or forefoot, and when forces were maximal. Arch
      height decreased from heel contact and increased after heel rise to its maximum
      at toe-off. CONCLUSIONS: The extent of forefoot segment motion confirms the
      significance of midfoot joints to normal foot function. Between foot flat and
      heel rise, the forefoot pattern of motion is indicative of foot stability.
      Typical foot motion does not obey descriptions of triplanar motion such as
      'pronation' and 'supination'. RELEVANCE: Typical stance phase foot motion has
      been described according to a forefoot:rearfoot model and rearfoot:leg model of
      motion, together with profiles of medial longitudinal arch height and ground
      reaction forces. This information can be applied in the management of foot
      dysfunction and should stimulate research into midfoot motion and overall control
      of the foot.

PMID- 11470302
TI  - Time course of stress relaxation and recovery in human ankles.
AB  - OBJECTIVE: To characterise the time course of stress relaxation and recovery from
      stress relaxation in human ankles. DESIGN: Two experiments were conducted. The
      first used a randomised within-subjects design, and the second used a randomised
      between-subjects regression design. BACKGROUND: Several studies have described
      the time course of stress relaxation in human joints, but most have looked only
      at the effects of short durations of stretch. The time course of recovery from
      stretch in human ankles has not been documented. METHODS: In the first
      experiment, one ankle of each of eight subjects was stretched to a fixed
      dorsiflexion angle for 20 min. The ankle was then released for 2 min (during
      which time subjects either remained relaxed or performed isometric contractions),
      then stretched again. In a second experiment, on 24 subjects, the ankle was
      stretched for 20 min, then released between 0 and 20 min, then stretched again.
      In both experiments, subjects remain relaxed and ankle torque was measured
      continuously. RESULTS: When a constant-angle stretch was applied to the ankle,
      torque declined bi-exponentially towards an asymptote that was 58% of the initial
      torque. Nearly 5 min of stretch were required to obtain half of the maximal
      possible stress relaxation. Torque had recovered by 43% within 2 min of the
      release of stretch, but the degree of recovery did not appear to depend on
      whether subjects remained relaxed or performed isometric contractions. The time
      course of recovery was similar to the time course of stress relaxation.
      CONCLUSIONS: Long duration stretches are required to produce a large proportion
      of the maximal possible stress relaxation. Recovery is initially rapid when the
      stretch is released. RELEVANCE: These data provide a description of the time
      course of the effects of stretch, and of the subsequent relief of stretch, on
      mechanical properties of human ankles.

PMID- 11470303
TI  - Acceleration of the calcaneus at heel strike in neutrally aligned and pes planus
      feet.
AB  - OBJECTIVE: The purpose of this research was twofold: (1) to study the impulsive
      acceleration of the calcaneus at heel strike in subjects with neutrally aligned
      (i.e., normal) feet and (2) to explore how the acceleration may differ in
      subjects with pes planus (i.e., flat) feet. The component of the acceleration
      vector aligned with the long axis of the tibia was quantified. DESIGN: Subjects
      with either foot type were instrumented and calcaneal acceleration was quantified
      during comfortable cadence locomotion. BACKGROUND: Aberrant peak acceleration has
      been associated with osteoarthritis. While tibial acceleration has been
      quantified, calcaneal acceleration has not. Additionally, foot morphology, or
      foot type, has demonstrated an effect on foot function and thus there may be
      differences in calcaneal acceleration between foot types. METHODS: Six subjects
      with neutrally aligned feet and six with pes planus feet were selected via a
      clinical exam. Accelerometers were attached to the posterior aspect of the medial
      surface of the calcanei bilaterally and 10 walking trials were collected.Results.
      The average baseline-to-peak acceleration for the neutrally aligned and pes
      planus feet was 4.79 g (SD, 2.14 g) and 5.24 g (SD, 3.28 g), respectively; the
      peak-to-peak acceleration was 5.03 g (SD, 2.74 g) and 6.75 g (SD, 3.89 g). There
      were no significant differences (P>0.05) between foot types. CONCLUSIONS: The
      calcaneal acceleration at heel strike for neutrally aligned and pes planus feet
      was not sensitive to foot type. RELEVANCE: Aberrant acceleration has been
      associated with the development of osteoarthritis [J. Biomech. 5 (3) (1972) 267;
      J. Biomech. 6 (1) (1973) 51; J. Biomech. 15 (7) (1982) 487]. Osteoarthritis at
      the subtalar joint, as well as the ankle and midtarsal joints, may be initiated
      and/or perpetuated by excessive calcaneal acceleration at heel strike.

PMID- 11470304
TI  - Stress distribution of the foot during mid-stance to push-off in barefoot gait: a
      3-D finite element analysis.
AB  - OBJECTIVE: To quantify stress distribution of the foot during mid-stance to push
      off in barefoot gait using 3-D finite element analysis. DESIGN: To simulate the
      foot structure and facilitate later consideration of footwear. Finite element
      model was generated and loading condition simulating barefoot gait during mid
      stance to push-off was used to quantify the stress distributions. BACKGROUND: A
      computational model can provide overall stress distributions of the foot subject
      to various loading conditions. METHODS: A preliminary 3-D finite element foot
      model was generated based on the computed tomography data of a male subject and
      the bone and soft tissue structures were modeled. Analysis was performed for
      loading condition simulating barefoot gait during mid-stance to push-off.
      RESULTS: The peak plantar pressure ranged from 374 to 1003 kPa and the peak von
      Mises stress in the bone ranged from 2.12 to 6.91 MPa at different instants. The
      plantar pressure patterns were similar to measurement result from previous
      literature. CONCLUSIONS: The present study provides a preliminary computational
      model that is capable of estimating the overall plantar pressure and bone stress
      distributions. It can also provide quantitative analysis for normal and
      pathological foot motion. RELEVANCE: This model can identify areas of increased
      pressure and correlate the pressure with foot pathology. Potential applications
      can be found in the study of foot deformities, footwear, surgical interventions.
      It may assist pre-treatment planning, design of pedorthotic appliances, and
      predict the treatment effect of foot orthosis.

PMID- 11470305
TI  - A surgical simulation system of skin sutures using a three-dimensional finite
      element method.
AB  - OBJECTIVE: To establish a surgical simulation system of skin sutures using a
      three-dimensional finite element method. DESIGN: Three-dimensional finite element
      models were developed from point data obtained with a rapid three-dimensional
      surface-measuring device and postoperative profiles were evaluated using these
      models. BACKGROUND: Since suturing a wound may result in undesirable skin
      extrusion, it is important to make the extrusion as inconspicuous as possible. We
      have investigated a means of determining appropriate suture methods to decrease
      the extrusion. METHODS: Affected body parts were measured non-invasively with a
      rapid three-dimensional surface-measuring device. Finite element models were
      prepared, and an appropriate method for reducing skin extrusion was evaluated by
      attempting various suturing methods. RESULTS: Two kinds of finite element models
      were prepared: a conventional spindle model and a modified S-shape model. The
      height of the extrusion of the modified S-shape model was decreased by 40% in
      comparison with that of the spindle model. These results agreed with clinical
      findings. CONCLUSIONS: Due to this surgical simulation system of skin sutures,
      with a rapid three-dimensional surface-measuring device and three-dimensional
      finite element analysis, it was possible to design an appropriate suturing method
      and to evaluate the postoperative skin profiles. The modified S-shape suture
      method would be a recommendable method. RELEVANCE: Using this surgical simulation
      system of skin sutures, a surgeon can evaluate an appropriate suturing method
      before operation. It is expected that this system will reduce a surgeon's labor.

PMID- 11470306
TI  - Reproducibility and validity of a new test protocol for measuring isokinetic
      trunk extension strength.
AB  - OBJECTIVE: To investigate the reproducibility and validity of isokinetic trunk
      extension strength scores obtained using a range of motion of 20 degrees and
      velocities of 10 and 40 degrees /s. BACKGROUND: Common protocols for testing
      trunk extension strength incorporate a range of motion of 40 degrees or more and
      test velocities of between 30 and 180 degrees/s. These test parameters may be
      neither necessary for portraying the strength profile of the muscles involved nor
      suitable for patients impaired with low back dysfunction. DESIGN: Test-retest of
      maximal concentric and eccentric isokinetic trunk extension strength in healthy
      subjects. METHODS: 17 women and 18 men were tested twice within 1-2 weeks. Tests
      were performed with subjects positioned in sitting. RESULTS: The trunk extension
      strength scores revealed excellent agreement with the expected physiological
      moment-velocity curve. On average women's trunk extension strength was 62% that
      of men (range: 59.3-64.4%). The test-retest correlation coefficients were
      generally higher in women (0.70-0.87) than in men (0.52-0.78) and significant at
      P=0.01. The standard error of measurement ranged between 13 and 21 N m for women
      and between 35 and 50 N m for men, which were equivalent to 9% and 15% of the
      mean strength in women and men, respectively. CONCLUSION: This study indicates
      that the present protocol may be validly applied in assessing trunk extension
      strength in normal women. RELEVANCE: Reproducible and valid trunk extension
      strength findings are essential if measurable strength deficiency of the
      extensors is to be formally accepted as an impairment. The present protocol
      incorporates or meets most of the relevant problems associated with trunk
      concentric and eccentric strength testing, and hence has the potential of
      becoming a standard method for clinical applications.

PMID- 11470308
TI  - Mechanisms by which metals promote events connected to neurodegenerative
      diseases.
AB  - Although the exact causative phenomenon responsible for the onset and progression
      of neurodegenerative disorders is at present unresolved, there are some clues as
      to the mechanisms underlying these chronic diseases. This review addresses
      mechanisms by which endogenous or environmental factors, through interaction with
      redox active metals, may initiate a common cascade of events terminating in
      neurodegeneration.

PMID- 11470309
TI  - Roles of the metallothionein family of proteins in the central nervous system.
AB  - Metallothioneins (MTs) constitute a family of proteins characterized by a high
      heavy metal [Zn(II), Cu(I)] content and also by an unusual cysteine abundance.
      Mammalian MTs are comprised of four major isoforms designated MT-1 trough MT-4.
      MT-1 and MT-2 are expressed in most tissues including the brain, whereas MT-3
      (also called growth inhibitory factor) and MT-4 are expressed predominantly in
      the central nervous system and in keratinizing epithelia, respectively. All MT
      isoforms have been implicated in disparate physiological functions, such as zinc
      and copper metabolism, protection against reactive oxygen species, or adaptation
      to stress. In the case of MT-3, an additional involvement of this isoform in
      neuromodulatory events and in the pathogenesis of Alzheimer's disease has also
      been suggested. It is essential to gain insight into how MTs are regulated in the
      brain in order to characterize MT functions, both in normal brain physiology, as
      well as in pathophysiological states. The focus of this review concerns the
      biology of the MT family in the context of their expression and functional roles
      in the central nervous system.

PMID- 11470310
TI  - Zinc-bound metallothioneins as potential biological markers of ageing.
AB  - Metallothioneins (MTs) (I+II) play pivotal roles in metal-related cell
      homeostasis because of their high affinity for metals forming clusters. The main
      functional role of MTs is to sequester and/or dispense zinc participating in zinc
      homeostasis. Consistent with this role, MT gene expression is transcriptionally
      induced by a variety of stressing agents to protect cells from reactive oxygen
      species. In order to accomplish this task, MTs induce the secretion of pro
      inflammatory cytokines by immune and brain cells, such as astrocytes, for a
      prompt response against oxidative stress. These cytokines are in turn involved in
      new synthesis of MTs in the liver and brain. Such protective mechanism occurs in
      the young-adult age, when stresses are transient. Stress-like condition is
      instead constant in the old age, and this causes continuous stealing of
      intracellular zinc by MTs and consequent low bioavailability of zinc ions for
      immune, endocrine, and cerebral functions. Therefore, a protective role of zinc
      bound MTs (I+II) during ageing can be questioned. Because free zinc ions are
      required for optimal efficiency of the immune-endocrine-nervous network, zinc
      bound MTs (I+II) may play a different role during ageing, switching from a
      protective to a deleterious one in immune, endocrine, and cerebral activities.
      Physiological zinc supply, performed cautiously, can correct deficiencies in the
      immune-neuroendocrine network and can improve cognitive performances during
      ageing and accelerated ageing. Altogether these data indicate that zinc-bound MTs
      (I+II) can be considered as novel potential markers of ageing.

PMID- 11470311
TI  - Iron and neurodegenerative disorders.
AB  - The brain shares with other organs the need for a constant and readily available
      supply of iron and has a similar array of proteins available to it for iron
      transport, storage, and regulation. However, unlike other organs, the brain
      places demands on iron availability that are regional, cellular, and age
      sensitive. Failure to meet these demands for iron with an adequate supply in a
      timely manner can result in persistent neurological and cognitive dysfunction.
      Consequently, the brain has developed mechanisms to maintain a continuous supply
      of iron. However, in a number of common neurodegenerative disorders, there
      appears to be an excess accumulation of iron in the brain that suggests a loss of
      the homeostatic mechanisms responsible for regulating iron in the brain. These
      systems are reviewed in this article. As a result of a loss in iron homeostasis,
      the brain becomes vulnerable to iron-induced oxidative stress. Oxidative stress
      is a confounding variable in understanding the cell death that may result
      directly from a specific disease and is a contributing factor to the disease
      process. The underlying pathogenic event in oxidative stress is cellular iron
      mismanagement.

PMID- 11470312
TI  - Copper and prion disease.
AB  - The prion protein is a cell surface glyco-protein expressed by neurones. Its
      function has remained elusive until it was recently shown to be a copper binding
      protein. There is now strong evidence that the prion protein has a role in normal
      brain copper metabolism. Prion protein expression alters copper uptake into cells
      and enhances copper incorporation into superoxide dismutase. Furthermore the
      prion protein itself can act as a superoxide dismutase. One aspect of prion
      disease is the conversion of functional prion protein into an aggregated amyloid.
      This conversion may alter the function of the prion protein or abolish it. These
      results suggest that prion disease may involve disturbance to brain copper
      homeostasis.

PMID- 11470313
TI  - Copper in disorders with neurological symptoms: Alzheimer's, Menkes, and Wilson
      diseases.
AB  - Copper is an essential element for the activity of a number of physiologically
      important enzymes. Enzyme-related malfunctions may contribute to severe
      neurological symptoms and neurological diseases: copper is a component of
      cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the
      essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide
      dismutase which plays a key role in the cellular response to oxidative stress by
      scavenging reactive oxygen species. Furthermore, copper is a constituent of
      dopamine-beta-hydroxylase, a critical enzyme in the catecholamine biosynthetic
      pathway. A detailed exploration of the biological importance and functional
      properties of proteins associated with neurological symptoms will have an
      important impact on understanding disease mechanisms and may accelerate
      development and testing of new therapeutic approaches. Copper binding proteins
      play important roles in the establishment and maintenance of metal-ion
      homeostasis, in deficiency disorders with neurological symptoms (Menkes disease,
      Wilson disease) and in neurodegenerative diseases (Alzheimer's disease). The
      Menkes and Wilson proteins have been characterized as copper transporters and the
      amyloid precursor protein (APP) of Alzheimer's disease has been proposed to work
      as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological
      observations in neurodegenerative disorders like Alzheimer's disease and in the
      genetically inherited copper-dependent disorders Menkes and Wilson disease are
      summarized. This could provide a rationale for a link between severely
      dysregulated metal-ion homeostasis and the selective neuronal pathology.

PMID- 11470314
TI  - Aluminium as a risk factor in Alzheimer's disease, with emphasis on drinking
      water.
AB  - Aluminium (Al) is clearly a powerful neurotoxicant. Considerable evidence exists
      that Al may play a role in the aetiology or pathogenesis of Alzheimer's disease
      (AD), but whether the link is causal is still open to debate. This paper reviews
      the epidemiological evidence linking Al and AD. Nine out of 13 published
      epidemiological studies of Al in drinking water and AD have shown statistically
      significant positive relations. Given the difficulty in producing high-quality
      data for the occurrence of AD and also for Al exposure, with the resulting
      unavoidable misclassification errors biasing any true association towards the
      null value, these studies are remarkably consistent. A major problem in their
      interpretation is that drinking water, even at high Al concentrations, only
      contributes a fraction of the total dietary intake of Al. In particular, regular
      consumers of antacids ingest gram amounts of Al daily, thousands of times the
      amounts taken in through drinking water, and epidemiological studies of antacid
      exposure and AD have been largely negative. However, Al is very poorly absorbed
      in the gastrointestinal tract, and the possibility that some Al fractions present
      in drinking water may be particularly bioavailable cannot be dismissed at
      present. The combined evidence linking Al and AD warrants substantial research
      efforts. Such efforts should focus on clarification of the cellular and molecular
      mechanisms in Al toxicity and of the basic metabolism and kinetics of Al in the
      human body, and on further epidemiological studies including diverse routes of Al
      exposure and also variables that are known or suspected to influence the
      individuals' susceptibility to AD, such as apolipoprotein E allele status and
      family history of AD.

PMID- 11470315
TI  - Neurotoxicity and molecular effects of methylmercury.
AB  - The neurotoxicity of high levels of methylmercury (MeHg) and the high
      susceptibility of the developing brain are well established both in humans and
      experimental animals. Prenatally poisoned children display a range of effects
      varying from severe cerebral palsy to subtle developmental delays. Still unknown
      is the lowest dose that impairs neurodevelopment. The primary source of human
      exposure is the fish. The data obtained so far from epidemiological studies on
      fish-eating populations are not consistent. A reference dose of 0.1 microg
      MeHg/kg per day has been established by the U.S. Environmental Protection Agency
      based on a study on Iraqi children exposed to MeHg in utero. However, these
      exposures occurred at high level for a limited period of time, and consequently
      were not typical of lower chronic exposure levels associated with fish
      consumption. Major obstacles for estimation of a threshold dose for MeHg include
      the delayed appearance of the neurodevelopmental effects following prenatal
      exposure and limited knowledge of cellular and molecular processes underlying
      these neurological changes. In this respect, a strategy which aims at identifying
      sensitive molecular targets of MeHg at environmentally relevant levels may prove
      particularly useful to risk assessment. Here some examples of MeHg molecular
      effects occurring at low doses/concentrations are presented.

PMID- 11470316
TI  - Effects of AlCl3 on toad skin, human erythrocytes, and model cell membranes.
AB  - Aluminum, a very abundant metal, could play a toxic role in several pathological
      processes, including neurodegeneration. Although the effects of Al(III) on
      biological membranes have been extensively described, direct information
      concerning the molecular basis of its biological activity is rather scanty. To
      examine aluminum challenges on cell membranes, various concentrations of AlCl3 in
      aqueous solutions were incubated with human erythrocytes, isolated toad skin, and
      molecular models of biomembranes. The latter consisted of multilayers of
      dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine,
      representing phospholipid classes located in the outer and inner monolayers of
      the human erythrocyte membrane. These specimens were studied by scanning electron
      microscopy, electrophysiological measurements, and x-ray diffraction. The results
      indicate that Al(III) in the concentration range of 10-100 microM induced the
      following structural and functional effects: (i) change in the normal discoid
      shape of human erythrocytes to echinocytes due to the accumulation of Al(III)
      ions in the outer moiety of the red cell membrane; (ii) perturbation of
      dimyristoylphosphatidylcholine, and to a lesser extent of
      dimyristoylphosphatidylethanolamine bilayers, and (iii) decrease in the short
      circuit current and in the potential difference of the isolated toad skin,
      effects that are in accordance with a time-dependent modulation of ion transport
      in response to changes in the molecular structure of the lipid bilayer.

PMID- 11470317
TI  - Effects of aluminum on the neurotoxicity of primary cultured neurons and on the
      aggregation of beta-amyloid protein.
AB  - Recent epidemiological, neuropathological, and biochemical studies have suggested
      a possible link between the neurotoxicity of aluminum and the pathogenesis of
      Alzheimer's disease. However, this relationship remains controversial. To
      investigate detailed characteristics of neurotoxicity of aluminum, we used
      primary cultured neurons of rat cerebral cortex as an in vitro model system for
      the observation of morphological changes induced by chronic exposure to aluminum.
      Although the exposure to aluminum chloride (10-100 microM) for 1 week did not
      cause marked neuronal death, degeneration of neuritic processes and accumulation
      of tau protein and beta-amyloid protein appeared after chronic exposure to 50
      microM aluminum chloride for more than 3 weeks. We also investigated the
      polymerization of beta-amyloid protein in vitro using the immunoblotting
      technique. We thus found that aluminum induced conformational changes in beta
      amyloid protein and enhanced its aggregation in vitro. The aggregated beta
      amyloid protein was dissolved by the addition of desferrioxamine, a chelator of
      aluminum. The aggregated beta-amyloid protein pre-incubated with aluminum formed
      fibrillar deposits on the surface of cultured neurons.

PMID- 11470318
TI  - The response of neurones and glial cells to elevated copper.
AB  - Defective copper excretion in Wilson's disease can result in increased
      neurological copper concentrations. This is thought to occur following exposure
      to increased circulating copper released from necrotic hepatocytes in a saturated
      liver. BU17 human glioma cells and SH-SY5Y human neuroblastoma cells were exposed
      to media supplemented with copper in the range 0-250 microM for periods up to 48
      h to investigate this hypothesis. Copper uptake, cell growth, intracellular
      radical generation, and oxidative stress were measured in copper exposed cells.
      No increase in copper uptake or inhibition of cell growth could be measured in
      either cell type at any time point or copper concentration investigated. However,
      significant increases in radical generation (p < 0.001) could be measured in both
      BU17 and SH-SY5Y cells. A decreased ability to cope when the cells were exposed
      to additional pro-oxidants suggested that the cells were under oxidative stress
      with significant reductions in cell viability following exposure to both copper
      and ascorbic acid. These data suggest that copper sequestration does not occur in
      neuronal cells exposed to elevated extracellular copper concentrations.

PMID- 11470319
TI  - Manganese toxicity is associated with mitochondrial dysfunction and DNA
      fragmentation in rat primary striatal neurons.
AB  - Manganese (Mn) in excess is toxic to neurons of the globus pallidus, leading to a
      Parkinsonian-like syndrome. We used rat primary neuron cultures to examine the
      cellular events following manganese exposure. Following exposure to Mn(2+) for 48
      h, striatal neurons showed dose-dependent losses of mitochondrial membrane
      potential and complex II activity. The Mn exposure effect on mitochondrial
      membrane potential was significant at every concentration measured (5, 50, and
      500 microM), and the manganese exposure effect on complex II activity was
      significant at 50 and 500 microM. Exposure of striatal neurons to both Mn(2+) and
      the complex II inhibitor 3-nitropropionic acid resulted in additive toxicity.
      Striatal neurons exposed to 5 microM Mn(2+) for 48 h exhibited DNA fragmentation
      and decreases in the immunohistochemically detectable microtubule-associated
      protein MAP-2. These results indicate that manganese may trigger apoptotic-like
      neuronal death secondary to mitochondrial dysfunction. Rescue of neurons by
      apoptosis inhibitors may be helpful in treating manganese toxicity and similar
      neurodegenerative processes.

PMID- 11470320
TI  - Aluminium incorporation into the brain of rat fetuses and sucklings.
AB  - Aluminium is highly neurotoxic and inhibits prenatal and postnatal development of
      the brain in humans and experimental animals. However, the incorporation of
      aluminium into the brain of fetuses and sucklings during gestation and lactation
      has not been well clarified because aluminium lacks a suitable isotope for a
      tracer experiment. In this study, we used 26Al (a radioisotope of aluminium with
      a half-life of 716,000 years) as a tracer, and measured 26Al incorporation into
      the brain of rat fetuses and sucklings by using accelerator mass spectrometry.
      26Al (26AlCl3) was subcutaneously injected into pregnant rats and lactating rats.
      By day 21 of gestation, considerable amounts of the 26Al injected into the
      pregnant rats had been transferred to the brain and nuclear fraction (brain cell
      nuclei) of the rat fetuses. From day 5 to day 20 postpartum, the amounts of 26Al
      measured in the brain of suckling rats increased significantly. On day 20
      postpartum, 26Al was found in the nuclear fraction isolated from the brain of
      suckling rats. It is concluded that 26Al subcutaneously injected into pregnant
      rats and/or lactating rats was incorporated into the brain and nuclear fraction
      (brain cell nuclei) of fetuses and sucklings through the transplacental passage
      and/or maternal milk.

PMID- 11470321
TI  - Prenatal exposure to methyl mercury in rats: focus on changes in kynurenine
      pathway.
AB  - Previous studies showed learning and memory deficits following prenatal exposure
      to methyl mercury (MMC) in rats. Considering the described dysfunction in several
      neurotransmission systems after MMC exposure, one can surmise that changes in the
      kynurenine pathway could also be involved in an altered brain functional
      development. Thus we focused our attention on the potential alteration in the
      production of tryptophan metabolites by prenatal MMC exposure. For this purpose,
      brains were removed, at postnatal days 21 and 60, from rats treated, at
      gestational day 8, with saline or a single dose of MMC (8 mg/kg). The levels of
      tryptophan, glutamic, aspartic, kynurenic, anthranilic, and quinolinic acids were
      determined in hippocampal tissues of both groups of rats. No change was detected
      in the concentration of aspartic, glutamic, and kynurenic acids in 21- and 60-day
      old exposed rats in comparison with age-matched controls. On the contrary, at 21
      days of age but not at 60 days, we found a very significant reduction of
      anthranilic acid and, in parallel, an increase of quinolinic acid levels in MMC
      exposed rats in comparison with control animals. Finally in the same brain area,
      tryptophan levels were significantly increased both at 21 and 60 days of
      postnatal life. These results suggest that an imbalance in the kynurenine pathway
      could be involved in the toxic effects induced by MMC on brain development.

PMID- 11470322
TI  - Complexities in the neurotoxic actions of 6-hydroxydopamine in relation to the
      cytoprotective properties of taurine.
AB  - The neurotoxin 6-hydroxydopamine was shown to cause an imbalance between the
      direct and indirect pathways of the striato-nigral system as evidenced by a
      decreased release of gamma-aminobutyric acid and taurine in the substantia nigra
      but not in the globus pallidus following neostriatal stimulation with kainate
      (100 microM). The neurotoxicity of 6-hydroxydopamine is generally believed to
      result from reactive-oxygen radical formation, although it is also known to
      inhibit mitochondrial NADH dehydrogenase. The release of Fe(II) from the
      unactivated form [3Fe(III)-4S] of cytoplasmic aconitase (EC(50) < 8 microM) was
      shown to be followed by the slower oxidation of thiol groups in the protein.
      Complete loss of -SH groups, and enzyme activity, was seen after incubation of
      glyceraldenyde-3-phosphate dehydrogenase with 200 microM 6-hydroxydopamine for 75
      min at 37 degrees C (IC(50) = 70.8 +/- 0.3 microM). Thus the cellular effects of
      6-hydroxydopamine are complex, involving impairment of mitochondrial function,
      iron- release, sulphydryl-group oxidation, and enzyme inhibition in addition to
      direct generation of reactive oxygen radicals. Taurine, which is known to be
      neuroprotective in some other systems, only affords protection against some of
      these effects, thereby explaining its reported ineffectiveness against 6
      hydroxydopamine toxicity.

PMID- 11470323
TI  - Enhanced brain regional lipid peroxidation in developing rats exposed to low
      level lead acetate.
AB  - Neurotoxicity associated with lead exposure may be the result of a series of
      small perturbations in brain metabolism, and, in particular, of oxidative stress.
      Some studies have suggested a lead-induced enhancement on lipid peroxidation as a
      possible mechanism for some toxic effects of lead. However, there are no reports
      about the association between lipid peroxidation enhancement and brain lead
      content. In this study, we determined the concentration of lead and the formation
      of lipid fluorescence products in the blood, as well as in the parietal cortex,
      striatum, hippocampus, thalamus, and cerebellum of rats exposed prenatally and
      postnatally to variable concentrations of lead acetate through drinking water.
      Pregnant Wistar rats were intoxicated throughout gestation with solutions
      containing either 320 or 160 ppm of lead. The pups were treated after birth in
      the same way until 45 days of age. Control animals received deionized water for
      the same period of time. The developing rats were sacrificed at postnatal day 45
      and lead level was assessed biochemically in the blood and different brain
      regions. Results showed that blood lead levels were increased in a dose-dependent
      manner. In the brain, lead accumulated preferentially in the parietal cortex,
      striatum, and thalamus as compared to the control group, while lipid fluorescence
      products were significantly increased in the striatum, thalamus, and hippocampus
      of the treated animals. These data suggest that in the brain of rats exposed to
      lead acetate, lead produces a neurotoxic effect with a complex correlation with
      both lead regional content and lipid peroxidation.

PMID- 11470324
TI  - Immunostaining of calmodulin and aluminium in Alzheimer's disease-affected
      brains.
AB  - Previous in vitro studies have shown that Al(3+) binds to calmodulin, inducing
      alterations in its capability to interact with target proteins, accompanied by
      loss of immunological recognition by its conformational specific monoclonal
      antibody CAM1. In spite of the wealth of data of calmodulin action in vitro,
      little information is available on the possible involvement of this protein in
      the pathology typical of Alzheimer's disease. In the present study, we
      investigated calmodulin immunoreactivity in post-mortem human brains affected by
      Alzheimer's disease, compared with age-matched control brains. Conformational
      monoclonal antibodies raised against Ca(2+)-calmodulin, namely CAM1 and CAM4,
      were used in this study for the characterization of calmodulin. Calmodulin
      immunorecognition by monoclonal antibody CAM1 was found to be lost in cortical
      tissue sample from brains affected by Alzheimer's disease. This finding leads to
      the hypothesis of a new, possibly inactive, conformation of the molecule during
      the disease. On the other hand, CAM4 immunoreactivity was decreased in neurons of
      brains affected by Alzheimer's disease. Anti-Al(3+) monoclonal antibodies
      revealed instead more marked aluminium immunoreactivity in the affected brains
      compared to normal ones. The loss of CAM1 immunoreactivity and the occurrence of
      large amounts of aluminium suggest an alteration of the active conformation of
      calmodulin in disease-affected brains. These alterations could be involved in the
      development of Alzheimer's disease pathology.

PMID- 11470325
TI  - Aluminium toxicity in the rat brain: histochemical and immunocytochemical
      evidence.
AB  - Although the neurotoxic actions of aluminium (Al) have been well documented, its
      contribution to neurodegenerative diseases such as Alzheimer's disease remains
      controversial. In the present study, we applied histochemical techniques to
      identify changes induced by intracerebroventricular Al injections (5.4 microg in
      5.5 microl, daily over a period of 5 successive days) in the adult rat brain
      after survival periods of either 1 or 6 weeks. For both Al- and saline-infused
      controls, no major signs of gross histological changes were evident in cresyl
      violet-stained sections. Al (as indicated by the fluorescent Morin staining) was
      concentrated in white matter of the medial striatum, corpus callosum, and
      cingulate bundle. Immunoreactivity of astrocytes and phagocytic microglia based
      on glial fibrillary acidic protein and ED1 markers, respectively, revealed a
      greater inflammatory response in Al-injected animals compared to controls. Damage
      of the cingulate bundle in Al-treated animals led to a severe anterograde
      degeneration of cholinergic terminals in cortex and hippocampus, as indicated by
      acetylcholinesterase labelling. Our data suggest that the enhancement of
      inflammation and the interference with cholinergic projections may be the modes
      of action through which Al may cause learning and memory deficits, and contribute
      to pathological processes in Alzheimer's disease.

PMID- 11470326
TI  - Neurotoxic effect of lead at low concentrations.
AB  - The effects of lead exposure at low concentrations were evaluated by studying the
      post-rotatory nystagmus (PRN) in two groups of rats exposed for 3 months to 50
      parts per million (ppm) of sodium acetate and 50 ppm of lead acetate,
      respectively, in the drinking water. Only animals treated with lead acetate
      showed changes of the PRN parameters which were significantly related to the
      concentration of lead in the blood and in brain structures. The patterns of PRN
      responses were characterized and classified into four types: progressively
      inhibitory (40%), prematurely inhibitory (25%), late inhibitory (25%), and
      excitatory-inhibitory (10%). No alterations of the PRN parameters were observed
      in the animals treated with sodium acetate. The results show that exposure to
      lead, even at low concentrations, impairs both sensory and motor functions. The
      findings also point out that the vestibular system and brain stem structures
      which generate and control the PRN represent targets of the action of this heavy
      metal. Finally, the results indicate that the evaluation of the vestibulo-ocular
      reflex can provide a test suited for the screening of the neurotoxic effects of
      lead even in the absence of clinical signs typical of lead intoxication.

PMID- 11470327
TI  - Participation of manganese-superoxide dismutase in the neuroprotection exerted by
      copper sulfate against 1-methyl 4-phenylpyridinium neurotoxicity.
AB  - Neurodegenerative effects of 1-methyl-4-phenylpyridinium (MPP+), the main
      metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      include enhancement of lipid peroxidation in the striatum of mice, associated to
      overproduction of free radicals. Copper acts as a prosthetic group of several
      copper-dependent antioxidant enzymes, and we previously showed the
      neuroprotective effect of CuSO4 pretreatment against the MPP+-induced
      neurotoxicity. In those studies, acute administration of CuSO4 (2.5 mg/kg)
      blocked MPP+-induced striatal lipid peroxidation, suggesting the activation of Cu
      dependent proteins that defend neurons from damage elicited by free radicals. In
      the present study, we evaluated the activity of superoxide dismutase in mice
      pretreated with CuSO4 16 h or 24 h prior to MPP+ administration. Copper
      administration produced a specific and significant increase in manganese
      superoxide dismutase activity in both the CuSO4/saline (fivefold increase) and
      the CuSO4/MPP+ groups of animals (sevenfold increase). The Na2SO4/MPP+ group
      showed a twofold increase in manganese superoxide dismutase activity versus
      control levels. The results suggest that the load of copper activating manganese
      dependent superoxide dismutase could be responsible for neuroprotection against
      the MPP+ insult.

PMID- 11470328
TI  - Effect of temperature on postanoxic, potentially neurotoxic changes of plasma pH
      and free iron level in newborn rats.
AB  - In asphyxiated newborns, iron, released from heme and ferritin and deposited in
      the brain, contributes to neurodegeneration. Because hypothermia provides
      neuroprotection, newborn mammals, showing reduced body temperature, might avoid
      iron-mediated neurotoxicity. However, hypothermia leads to acidosis, which
      induces hyperferremia. Therefore, we decided to study the effects of body
      temperature on plasma pH and iron levels in newborn rats exposed to a critical
      anoxia. Rectal temperature was kept at 33 degrees C (typical of neonates),
      reduced by 2 degrees C, or elevated to a level typical of healthy (37 degrees C)
      or febrile (39 degrees C) adults. Arterial blood samples were collected at 0, 10,
      20, 30, and 120 min postanoxia. Control samples were obtained from normoxic,
      temperature-matched neonates. Anoxia tolerance time decreased progressively at
      rectal temperatures exceeding 33 degrees C. Neither pH nor plasma iron were
      significantly affected by anoxia at 33 degrees C. Although hypothermia (31
      degrees C) resulted in acidosis in normoxic rats, both pH and iron levels were
      hardly influenced by anoxia. However, acidosis and hyperferremia, proportional to
      body temperature, developed at 37 and 39 degrees C. In conclusion, reduced body
      temperature is likely to protect asphyxiated newborns against iron-mediated brain
      injury.

PMID- 11470329
TI  - Deprivation and denervation differentially affect zinc-containing circuitries in
      the barrel cortex of mice.
AB  - In the neocortex, a population of glutamatergic synapses contains chelatable zinc
      that is released upon depolarization. The present study compares the effect of
      chronic tactile deprivation and vibrissectomy performed at different postnatal
      ages on the synaptic zinc distribution in the mouse barrel cortex. We found that
      a chronic unilateral tactile deprivation resulted in an increase of synaptic zinc
      in deprived barrels. Distribution and intensity of zinc staining in non-deprived
      barrels resembled the control situation. The increase of zinc staining was
      observed if chronic deprivation started in early postnatal life or in adolescent
      mice but not in 70-day-old animals. This suggests that a critical period exists
      for plasticity of zinc containing terminals in the barrel cortex. The alteration
      of zinc staining was localized to not only the thalamorecipient layers IV but
      also layer II/III, and upper layer V. Neonatal denervation of selected vibrissal
      rows resulted in rearrangement of synaptic zinc distribution following
      cytoarchitectonic alterations in the barrel field. However, no changes in the
      intensity of zinc staining were observed. Vibrissectomy performed after the
      critical period for barrel formation did not affect either the distribution or
      intensity of zinc staining. It appears that the integrity of vibrissa-barrel
      pathway is necessary to induce activity-dependent alterations in synaptic zinc.

PMID- 11470330
TI  - Antidepressant-like properties of zinc in rodent forced swim test.
AB  - The effects of zinc, the N-methyl-D-aspartate glutamate receptor inhibitor, were
      studied in mice and rats using the forced swim test. Zinc (ZnSO4) in a dose of 30
      mg/kg and imipramine (30 mg/kg), reduced the immobility time in the forced swim
      test in both species. Moreover, combined treatment in this test with zinc and
      imipramine at their ineffective doses (1 and 5 mg/kg, respectively) induced a
      statistically significant effect in rats. The doses active in the forced swim
      test reduced (in mice) or did not affect (in rats) locomotor activity. The
      results obtained indicate that zinc induces an antidepressant-like effect and
      enhances the effect of imipramine in the forced swim test, suggesting a potential
      antidepressant activity of zinc in humans.

PMID- 11470331
TI  - The effects of sodium arsenite exposure on behavioral parameters in the rat.
AB  - Arsenic is a metalloid widely present in the environment. It is found in well
      water, soil, and air, and is also released from mining residues and industrial
      debris, among other anthropogenic sources. It has been previously reported that
      the content of catecholamines in striatum, hippocampus, and other cerebral
      regions changes in mice and rats exposed to arsenic. Few studies have examined
      behavioral alterations after intoxication with arsenic, and both increased and
      decreased locomotor activity, as well as learning deficits, have been described.
      In order to characterize the behavioral alterations induced by arsenic exposure,
      we exposed adult male Sprague-Dawley rats to 5, 10, and 20 mg/kg of arsenic by
      intragastric route for 2 or 4 weeks. Exposed rats showed reduced locomotor
      activity, which returned to control levels at the end of the intoxication period.
      We also found an increase in the number of errors in an egocentric task,
      alterations in monoamine content in midbrain and cortex, and increases in arsenic
      brain concentration, which were related to time of the exposure but not dose.
      These results indicate that short-term arsenic exposure induces neural and
      behavioral changes that may reflect a neurotoxic effect, and that these
      alterations are correlated to dose, time of exposure, and experimental
      conditions.

PMID- 11470332
TI  - The distribution patterns of trace elements in the brain and erythrocytes in a
      rat experimental model of iodine deficiency.
AB  - Cretinism is a disease characterized by neurological defects associated with
      severe iodine deficiency. In a rat model of severe iodine deficiency, we
      investigated the distribution pattern of trace elements (iodine [I], selenium
      [Se], and bromine [Br] in brain tissue samples; potassium [K], calcium [Ca],
      manganese [Mn], iron [Fe], copper [Cu], zinc [Zn], rubidium [Rb], and lead [Pb]
      in erythrocytes) after supplementing the rats with I and/or Se. Neutron
      activation analysis, proton induced x-ray emission and x-ray fluorescence were
      used. The serum levels of total and free thyroxine (T4, FT4), and of total, free,
      and reverse triiodothyronine (T3, FT3, rT3, respectively) were assessed by
      radioimmunoassay. The results were statistically evaluated by one-way analysis of
      variance and bivariate correlation. The study indicated that the levels of T4,
      FT4, and rT3 increased in the serum of iodine-deficient rats supplemented with I
      or I + Se. In the same animals, we documented alterations of the content of Br in
      the brain, and of Zn, Mn, Cu, and Rb in erythrocytes, whereas the brain content
      of I and Se was unchanged. Thus, I and I + Se supplementation improves thyroid
      hormone metabolism but affects the content of selected trace elements in
      erythrocytes and of Br in the brain. The data stimulate further clarification of
      the role of trace elements in the central nervous system.

PMID- 11470333
TI  - Immune-endocrine status and coeliac disease in children with Down's syndrome:
      relationships with zinc and cognitive efficiency.
AB  - Immune defects, thyroid abnormalities, plasma zinc levels, and the presence of
      gastrointestinal disease were investigated in 43 children with Down's syndrome
      (DS). Peripheral T lymphocytes with the phenotype of helper cells or cluster of
      differentiation 4 (CD4) were decreased. Circulating activated T cells (CD3/HLA-DR
      positive cells) and large granular lymphocytes (CD16/CD56 positive cells) were
      increased. Plasma levels of interleukin-6 were higher in DS children than in
      controls. Serum levels of thyroid-stimulating hormone were increased in DS.
      Coeliac disease was over-represented in the group of DS children and many of
      these children also showed increased serum levels of immunoglobulin-G (IgG)
      specific for gliadin antigen. The increment of serum interleukin-6 was age
      related and correlated with anti-gliadin IgG levels in DS. Plasma zinc levels
      were lower in DS children with coeliac disease and in those with anti-gliadin IgG
      than in DS without detectable anti-gliadin IgG. Dietary antigens may represent a
      continuous stimulus for the immune system in this syndrome and interfere with
      normal immune responses. Altered intestinal absorption of nutrients may in turn
      affect endocrine functions, brain development, and cognitive performances.

PMID- 11470334
TI  - Serum concentrations of some metals and steroids in patients with chronic fatigue
      syndrome with reference to neurological and cognitive abnormalities.
AB  - Chronic fatigue syndrome is defined by the Atlanta Centers for Disease Control
      (Atlanta, GA, USA) as debilitating fatigue lasting for longer than 6 months.
      Symptoms include disturbances of cognition. Certain factors have in the past been
      shown to influence cognition, including metals such as aluminum, iron, and zinc;
      and steroids such as dehydroepiandrosterone. In the present study, concentrations
      of these factors were determined in the serum and plasma of patients and their
      age- and gender-matched healthy controls (10 women and 5 men in each group). In
      addition, copper, dehydroepiandrosterone sulphate, cortisol, cholesterol,
      hemoglobin, ferritin and transferrin concentrations, as well as transferrin
      genetic subtypes were determined in both groups. The results indicate that
      patients had significantly increased serum aluminum and decreased iron compared
      to controls. In the females, serum iron and dehydroepiandrosterone sulphate were
      significantly decreased and correlated. Total cholesterol was significantly
      increased, and significantly negatively correlated with dehydroepiandrosterone
      sulphate. There were no differences in zinc, copper, cortisol, hemoglobin,
      transferrin and ferritin concentrations, or in transferrin genetic subtypes.

PMID- 11470335
TI  - Sleep problems and substance use in adolescence.
AB  - Longitudinal studies of adults have reported finding insomnia to significantly
      predict onset of substance abuse. This study estimated the association between
      sleep problems and substance use among adolescents in the context of psychiatric
      problems. Data come from the US National Household Survey on Drug Abuse 1994-1996
      that included 13,831 adolescents. Use of cigarettes, alcohol and any illicit drug
      were each associated with adolescents' reports of having frequent sleep problems,
      adjusting for age, sex, race and family income (odds ratios ranging from 1.5 to
      3.8). Adjusting for internalizing (e.g. depression and anxiety) and externalizing
      (e.g. deviance and aggression) problems reduced the associations between sleep
      problems and use of these substances, suggesting that part of the association is
      attributable to psychiatric problems. The part of the association not
      attributable to psychiatric problems was limited to the associations between
      sleep problems and use of illicit drugs. These results suggest that the
      relationship between sleep problems and drug use/abuse must be viewed in the
      context of psychiatric problems. Longitudinal research that employs more specific
      measures of sleep problems is indicated. Such research may provide information on
      the relationship of sleep problems to the immediate health and well being of
      adolescents, as well as their trajectories into adulthood.

PMID- 11470336
TI  - Drugs and the dance music scene: a survey of current drug use patterns among a
      sample of dance music enthusiasts in the UK.
AB  - This study explores the utility of a self-completion survey method to quickly and
      cheaply generate information on patterns and trends among regular "recreational"
      drug consumers. Data is reported here from 1151 subjects accessed through a dance
      music publication. In keeping with previous studies of drug use within the dance
      scene polysubstance use was the norm. Many of those reporting use of "ecstasy"
      were regularly using multiple tablets often consumed in combination with other
      substances thus exposing themselves to serious health risks, in particular the
      risk of dose related neurotoxic effects. Seventy percent were drinking alcohol at
      hazardous levels. Subjects' patterns of drug purchasing also put them at risk of
      severe criminal sanction. Data supported evidence that cocaine use had become
      increasing popular in the UK, but contrasted with some commentators' views that
      ecstasy use was in decline. The utility of this method and how the results should
      be interpreted is discussed, as are the data's implications for harm and risk
      reduction activities.

PMID- 11470337
TI  - Illicit drugs and fitness to drive: assessment in Spanish Medical Driving Test
      Centres.
AB  - This study investigated the incidence of problems related to illicit drugs and
      fitness to drive among 8043 Spanish drivers assessed in 25 Medical Driving Test
      Centres at national level. In accordance with Spanish and European Union
      legislation, driving licences cannot be issued or renewed to people suffering
      from illicit drug-related problems. A small percentage (0.3%; n=24) of drivers
      interviewed had problems relating to drug use (abuse, dependence and induced
      disorders) and half of them (n=12) were also diagnosed as having problems with
      alcohol. Drivers with illicit drug-related problems were more often involved in
      road accidents and committed more traffic infractions during the last year
      (33.3%, n=8, and 79.2%, n=19, respectively) than those without problems related
      to illegal drug taking (12.3%, n=986, and 9.3%, n=748, respectively). Of drivers
      with drug problems 70.8% (n=17) were considered fit to drive. The results show
      that the incidence of drug-related problems is rare among Spanish drivers, and
      that in three out of four cases drivers with drug-related problems were
      considered fit to drive.

PMID- 11470338
TI  - Effect of chronic ethanol ingestion and exercise training on skeletal muscle in
      rat.
AB  - The aim of this study was to investigate the interactive effects of exercise
      training and chronic ethanol consumption on metabolism, capillarity, and
      myofibrillar composition in rat limb muscles. Male Wistar rats were treated in
      separate groups as follows: non exercised-control; ethanol (15%) in animals'
      drinking water for 12 weeks; exercise training in treadmill and ethanol
      administration plus exercise for 12 weeks. Ethanol administration decreased
      capillarity and increased piruvate kinase and lactate dehydrogenase activities in
      white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase
      activity and decreased cross-sectional area of type I, IIa, and IIb fibres.
      Exercise increased capillarity in all four limb muscles and decreased type I
      fibre area in plantaris. The decreased capillarity effect induced by ethanol in
      some muscles, was ameliorated when alcohol was combined with exercise. While
      alcoholic myopathy affects predominantly type IIb fibres, ethanol administration
      and aerobic exercise in some cases can affect type I and type IIa fibre areas.
      The exercise can decrease some harmful effects produced by ethanol in the muscle,
      including the decrease in the fibre area and capillary density.

PMID- 11470339
TI  - The efficacy of computer-tailored smoking cessation material as a supplement to
      nicotine patch therapy.
AB  - The study evaluated the efficacy of the Committed Quitters Program (CQP), a
      computer-tailored set of printed behavioral support materials offered free to
      purchasers of NicoDerm CQ patches, as a supplement to the nicotine patch and the
      standard brief User's Guide (UG) and audiotape. Callers to the CQP enrollment
      were randomized to either CQP (n=1854) or just the UG (n=1829). Abstinence and
      use of program materials were assessed by telephone interview at 6 and 12 weeks
      (the latter falling 2 weeks after patch use was to be discontinued). Considering
      all respondents, abstinence rates did not differ significantly between the UG and
      CQP groups. As expected, among those who reported they used their assigned
      materials (80.1% of the sample) smokers who received CQP demonstrated higher quit
      rates at both 6 weeks (38.8% v. 30.7%) and 12 weeks (18.2% v. 11.1%), compared to
      the UG group. Among those who used it, the Committed Quitters Program proved to
      be an effective behavioral treatment, improving quit rates over nicotine
      replacement therapy and a brief untailored written guide and audiotape.

PMID- 11470340
TI  - Social relationships and intravenous drug use among methadone maintenance
      patients.
AB  - This study examined the extent to which social relationships were associated with
      continued injection drug use and needle sharing among 252 methadone maintenance
      patients. Logistic regression analyses indicated that drug use was highest among
      persons who had a substance using live-in partner and among those with more drug
      using social relationships. Among injectors, whites and those who had more people
      present during IV drug use were more likely to share needles, while those with
      more emotional support were less likely to do so. These findings suggest that
      personal relationships strongly influence continued injection drug use and that
      methadone programs should help patients develop social networks of non-users.

PMID- 11470341
TI  - Access to medical care and service utilization among injection drug users with
      HIV/AIDS.
AB  - Access to care and optimal service utilization among 287 low income African
      American former and current drug injectors was examined. Results indicated
      suboptimal outpatient care, and no evidence of alternative use of hospital
      services. Participation in drug treatment and case management were associated
      with greater access to care and use of outpatient services, even after
      controlling for current drug use, gender, and insurance. AIDS and physical
      functioning limitation were associated with emergency room (ER) use and
      hospitalization. Participation in drug treatment and case management and an AIDS
      diagnosis were associated with optimal outpatient service use. Daily alcohol use
      was associated with ER as the usual facility for care. Integration of substance
      abuse treatment, case management, and medical services delivery may contribute to
      improved HIV care for this population.

PMID- 11470342
TI  - Neuroendocrine effects of d-fenfluramine and bromocriptine following repeated
      smoked cocaine in humans.
AB  - To study the consequences of repeated smoked cocaine use on central serotonergic
      and dopaminergic function, the effects of d-fenfluramine (d-FEN) and
      bromocriptine on plasma hormones were determined at three time-points following
      repeated cocaine self-administration under carefully controlled conditions. In a
      20-day inpatient study, male cocaine abusers (d-FEN: n=10; bromocriptine: n=8)
      self-administered smoked cocaine (12-50 mg) for 3 days followed by 2 weeks of
      abstinence. The acute effects of d-FEN (0 or 30 mg po) or bromocriptine (0 or
      1.25 mg po) on plasma neuroendocrine levels were determined 1-2, 7-8, and 13-14
      days after the last cocaine dose. Blood was drawn before and then every 30-60 min
      for 4 h after capsule administration. The effects of d-FEN and bromocriptine were
      also determined in healthy, outpatient controls; d-FEN was removed from medical
      use in the US midway through the study due to complications associated with
      chronic administration, so all of the control participants were tested in Italy.
      Cocaine users had a blunted prolactin and cortisol response to d-FEN that lasted
      for at least 2 weeks of cocaine abstinence, but had a normal response to
      bromocriptine, which suppressed prolactin by 50% of baseline. The long-lasting
      and selective disruptions in serotonin pathways following chronic cocaine use may
      provide a neurochemical basis for changes in mood commonly reported during
      cocaine withdrawal.

PMID- 11470343
TI  - Comorbid disruptive behavior disorder symptoms and their relationship to
      adolescent alcohol use disorders.
AB  - This investigation evaluated the relationship between comorbid Disruptive
      Behavior Disorder (DBD) and Alcohol Use Disorder (AUD) symptoms in adolescents.
      The factor structure of both DBD and AUD symptoms was evaluated and a structural
      model then examined the relationships between comorbid DBD symptoms and AUD
      symptoms. A full model and a sex differentiated model were evaluated. For the
      full model, only Conduct Disorder (CD) symptoms were associated with AUD
      symptoms. In the sex differentiated model, male adolescents demonstrated direct
      effects of CD and Attention Deficit Hyperactivity Disorder (ADHD) on AUD. For
      female adolescents we found only a robust direct effect of CD on AUD. We
      concluded that CD symptoms have the strongest concurrent association with AUD
      symptoms in adolescents. However, there is preliminary evidence of sex
      heterogeneity.

PMID- 11470344
TI  - Within- and between-subject variability in the reinforcing and subjective effects
      of nitrous oxide in healthy volunteers.
AB  - Within- and between-subject variability in the reinforcing and subjective effects
      of nitrous oxide (N(2)O) was studied across five sessions. Twelve volunteers with
      no history of drug dependence sampled 30% N(2)O and 100% oxygen for 10 min each,
      then chose nine times, once every 5 min, among N(2)O (e.g. "Agent A"), oxygen
      (e.g. "Agent B"), or "drug-free air." Choice varied across subjects but was
      stable within subjects. Quantitative differences in subjective effects occurred
      within and across subjects. Some subjective effects were correlated with choice
      and/or differed between subjects who were consistent choosers of N(2)O versus
      those who were not. However, drug liking and euphoria, two face-valid measures of
      abuse liability, were unrelated to choice. Thus, the present study found
      individual differences (i.e. between-subject variability) in subjective and
      reinforcing effects of N(2)O and, in terms of within-subject variability,
      suggested that subjective effects fluctuate across sessions to a relatively
      greater extent than do reinforcing effects. The varying degrees of correlation
      between N(2)O choice and its subjective effects emphasize the need for obtaining
      multiple measures when characterizing abuse liability of this drug.

PMID- 11470345
TI  - Intimate relationship characteristics associated with condom use among drug users
      and their sex partners: a multilevel analysis.
AB  - Few studies have examined sexual risk behaviors among drug users in the context
      of their primary sexual relationships. The aim of this study is to examine
      characteristics of sexual partners associated with inconsistent condom use among
      a sample of 703 cocaine and opiate users from Baltimore, MD who participated in a
      network oriented intervention study of human immunodeficiency syndrome (HIV) risk
      behaviors among drug users. The current study examines relationship
      characteristics between drug users and their sexual partners (n=1003). Some of
      the study participants had more than one sexual partner, accounting for the
      greater number of sexual pairs than study participants. Study participants
      reported using multiple drugs (56% injected, 48% sniffed heroin, and 48% smoked
      crack) and that 70% of their sexual partners also used heroin and/or cocaine.
      Forty percent reported consistent condom use in the past 3 months. In multiple
      logistic regression, characteristics associated with consistent condom use were,
      the drug user being HIV infected; not living with their sexual partners; and not
      being financially interdependent. Previous research has demonstrated lower rates
      of condom use with main compared with casual and exchange partners. Primary
      sexual partners provide a sense of stability and introducing condoms may not be
      desirable or realistic. HIV prevention programs that target drug users should
      focus on the benefits, such as trust and a sense of security, and risks of not
      using condoms in primary relationships. Programs should also focus on enhancing
      communication and negotiation skills through targeting individuals as well as
      couples.

PMID- 11470346
TI  - Onset and pattern of substance use in intravenous drug users of an opiate
      maintenance program.
AB  - OBJECTIVES: To assess the initiation of substance use of participants in an
      opiate maintenance program by a cross-sectional survey. METHOD: Participants
      (n=184) filled out a questionnaire assessing age at initial substance use and age
      at onset of regular drug use. RESULTS: Of 15 substances investigated, alcohol,
      nicotine, analgesics and marijuana were initiated and consumed regularly before
      the age of 18 years. Barbiturates, benzodiazepines, cocaine, and opiates were
      begun later. The time gap between initial and regular use varied depending on the
      substance. Regular use exceeded 50% for alcohol, benzodiazepines, cocaine,
      heroin, marijuana and nicotine. CONCLUSIONS: Specific knowledge about the age of
      onset and sequence of substances used by drug addicts may help to prevent
      substance use more age specifically.

PMID- 11470347
TI  - Limits to buprenorphine dosing: a comparison between quintuple and sextuple the
      maintenance dose every 5 days.
AB  - The relative efficacy of quintuple and sextuple buprenorphine dosing in abating
      withdrawal symptoms for 120 h was compared in opioid-dependent outpatients.
      Fourteen subjects received buprenorphine in a double-blind, placebo-controlled,
      cross-over design. Daily sublingual maintenance doses were 4 mg/70 kg (n=4) and 8
      mg/70 kg (n=10). After a stabilization period of daily maintenance
      administration, subjects received quintuple (5x daily maintenance dose) and
      sextuple (6x daily maintenance dose) doses every 120 h. Measures of opioid
      agonist and withdrawal effects were assessed daily. Subjective ratings of
      withdrawal were significantly greater than baseline ratings beyond 96-h post
      dosing under both regimens. There was no evidence, however, that those subjective
      ratings of withdrawal differed between the two regimens. Thus, these data suggest
      that sextuple buprenorphine dosing, administered every 5 days, does not abate
      opioid-withdrawal beyond 96 hours.

PMID- 11470348
TI  - Injection drug users: hospital care and charges.
AB  - Injection drug users have high rates of hospital use, however, the specific
      contribution of injection-related infections to hospitalization has never been
      determined. After reviewing 92 consecutive admissions of HIV-negative injection
      drug users to Rhode Island Hospital in 1998, we found that 49% were related to
      infections and an additional 24% were due to the biological effects of the
      injected drug. Admissions that were for injection-related infections were
      significantly more costly than other admissions of injection drug users ($13958
      vs. $7906). We conclude that considerable savings may result from preventative
      care of this population, including instruction in skin-cleaning techniques.

PMID- 11470349
TI  - Role of fimbriae as antigens and intestinal colonization factors of Salmonella
      serovars.

PMID- 11470350
TI  - RNA recovery and detection of mRNA by RT-PCR from preserved prokaryotic samples.
AB  - The effectiveness of maintaining prokaryotic RNA in Synechococcus and Pseudomonas
      cells, fixed in 96% ethanol, 4% paraformaldehyde, or suspended in RNAlater, and
      held in cold storage for 3 months was compared. Fluorometric determination of the
      RNA extracted from Synechococcus and Pseudomonas cells indicated that the cell
      storage treatments tested were equally effective at maintaining their total RNA
      content. There was not any detectable decrease in the quantity of RNA isolated
      from the preserved samples during storage. Intact mRNA transcripts of the RuBisCO
      (rbcL) and nir genes were detected by reverse transcriptase-polymerase chain
      reaction (RT-PCR) from preserved bacterial cells throughout 3 months of storage.
      In contrast, RT-PCR failed to amplify the mRNA of the rbcL and nitrite reductase
      genes in unfixed and/or unpreserved bacterial samples, suggesting that bacterial
      mRNA can be well maintained during a prolonged storage when cells are preserved
      properly. In addition, RNAlater is a useful reagent for the storage and
      maintenance of high quality RNA in unfrozen samples.

PMID- 11470351
TI  - Effect of oxygen level on simultaneous nitrogenase and sMMO expression and
      activity in Methylosinus trichosporium OB3b and its sMMO(C) mutant, PP319:
      aerotolerant N2 fixation in PP319.
AB  - Soluble methane monooxygenase (sMMO) expression and activity were monitored under
      conditions that either promoted or suppressed the expression of nitrogenase in
      Methylosinus trichosporium OB3b wild-type (WT) and in its sMMO-constitutive
      mutant, PP319. Both WT and mutant cultures had reduced sMMO activity and protein
      levels under elevated O2 conditions (188 microM) compared with low O2 conditions
      (24 microM). Simultaneous N2 fixation also reduced sMMO activity in both cultures
      when O2 was low. However, when O2 levels were increased, nitrogenase expression
      ceased and sMMO activity was reduced by approximately 77% in the WT, whereas sMMO
      and nitrogenase expression and activity in PP319 were relatively unaffected by
      the higher O2 levels. Western immunoblot analysis showed that the nitrogenase Fe
      protein resolved as two components (apparent molecular mass of 30.5 and 32 kDa)
      in both the WT and PP319 when O2 levels were low. When O2 levels were high, only
      the 32-kDa form of the Fe protein was present in PP319, whereas neither form was
      detectable in the WT. Aerotolerant N2 fixation appears to be associated with the
      32-kDa Fe protein in M. trichosporium OB3b.

PMID- 11470352
TI  - First evidence for a restriction-modification system in Leptospira sp.
AB  - The LE1 leptophage exhibited a host range restricted to the saprophytic
      Leptospira biflexa [Saint Girons et al., Res. Microbiol. 141 (1990) 1131-1133]
      and mainly to the Patoc 1 strain (hereafter called PFRA) kept in the Paris,
      France collection. Results of titration of LE1 lysates indicated the presence of
      a host-controlled modification and restriction system within PUSA (Patoc 1 strain
      maintained in the Morgantown, WV, USA collection) that was absent in PFRA.
      Because genomic DNA of PITAL (Patoc 1 strain maintained in Trieste, Italy)
      appeared smeared in pulsed field gel electrophoresis (PFGE), this strain is
      likely to contain nucleases that are activated upon DNA isolation. Moreover,
      comparative NotI digestions of PUSA and PFRA DNAs, as visualized by PFGE,
      indicated that PUSA belonged to a different serovar than PFRA. Finally, 16S
      ribosomal sequence analysis indicated that PUSA belonged to the saprophytic
      Leptospira meyeri species, while PITAL and PFRA appertained to L. biflexa. The
      evolutionary significance and the importance of the restriction and modification
      enzymes or non-specific nucleases within strains for genetic experiments are
      discussed.

PMID- 11470353
TI  - Study of mycoloyl transferase transport across the cell envelope of
      Corynebacterium glutamicum.
AB  - PS1 is a major exported protein of Corynebacterium glutamicum homologous to
      mycobacterial antigen 85. It is largely associated with the mycolic acid
      containing cell wall and acts as a mycoloyl transferase. The transport of PS1 to
      the cell wall is slow and occurs through two energetically distinct steps: the
      first one, which includes processing by signal peptidase, is rapid and inhibited
      by sodium azide or carbonyl cyanide m-chlorophenylhydrazone. This step is
      probably associated with translocation across the cytoplasmic membrane. The
      kinetics of the second step depend on the size of the polypeptide chain to be
      transported but neither ATP nor proton motive force is required. This step may
      correspond to the diffusion of PS1 across the cell wall to its final location.

PMID- 11470354
TI  - Methyl chloride utilising bacteria are ubiquitous in the natural environment.
AB  - Enrichment and isolation of methyl chloride utilising bacteria from a variety of
      pristine terrestrial, freshwater, estuarine and marine environments resulted in
      the detection of six new methyl chloride utilising Hyphomicrobium strains, strain
      CMC related to Aminobacter spp. and to two previously isolated methyl halide
      utilising bacteria CC495 and IMB-1, and a Gram-positive isolate SAC-4
      phylogenetically related to Nocardioides spp. All the pristine environments
      sampled for enrichment resulted in the successful isolation of methyl chloride
      utilising organisms.

PMID- 11470355
TI  - Choline deficiency induced by Mycoplasma fermentans enhances apoptosis of rat
      astrocytes.
AB  - A choline uptake system accumulating free choline in an energy-dependent process
      is described in Mycoplasma fermentans. The uptake system has a K(m) of 2.2x10(-5)
      M and a V(max) of 0.15 nmol 10 min(-1) mg(-1) cell protein and the choline
      incorporated could be recovered in the soluble fraction as free choline,
      phosphorylcholine and CDP-choline. Choline accumulation by M. fermentans resulted
      in a marked choline depletion of the growth medium. The choline depletion of an
      astrocyte cell culture induced by M. fermentans was associated with the apoptotic
      death of the cells. Apoptosis was not obtained with heat-inactivated mycoplasmas
      and could be reversed by the addition of free choline to the growth medium.

PMID- 11470356
TI  - Diversity of surface structures and virulence genetic markers among
      enteroaggregative Escherichia coli (EAEC) strains with and without the EAEC DNA
      probe sequence.
AB  - The expression of surface structures and the presence of DNA sequences related to
      putative virulence factors were investigated in 22 enteroaggregative Escherichia
      coli strains (EAEC). Fimbria was the most frequent (72.7%) structure identified.
      Only strains hybridising with the EAEC DNA probe carried aggA, but one strain
      produced a similar but unrelated bundle-like structure. All probe-positive and
      62.5% of the probe-negative strains carried the virulence genes tested; aspU and
      irp2 prevailed among the former strains. The EAEC probe-positive strains were
      more diverse, and some of these strains, which promoted cell detachment, also
      carried the hly and pap sequences, thus suggesting they might represent
      uropathogenic E. coli.

PMID- 11470357
TI  - Proteolytic activity among various oral Treponema species and cloning of a prtP
      like gene of Treponema socranskii subsp. socranskii.
AB  - The proteolytic activity of 11 treponemal strains representing different
      phylogenetic groups was investigated by SDS-polyacrylamide gel electrophoresis
      with copolymerised casein, gelatin and fibrinogen as substrates. The activity was
      specified to be trypsin- and chymotrypsin-like by the cleavage of synthetic
      substrates BAPNA and SAAPFNA, respectively. Nine strains degrade casein and the
      synthetic substrate BAPNA. Chymotrypsin-like activity specifically inhibited by
      phenylmethylsulfonyl fluoride was found in four treponemes. Southern blot
      analysis using a Treponema socranskii subsp. socranskii-specific prtP probe
      confirmed the presence of prtP homologous genes in these four strains. The
      internal fragments of the chymotrypsin-like protease genes were cloned and
      sequenced after PCR amplification. Here we report the cloning of the complete
      prtP-like gene of T. socranskii subsp. socranskii, an organism shown to possess
      epidemiologic relevance in periodontitis.

PMID- 11470358
TI  - Role played by the response regulator Ris in Bordetella bronchiseptica resistance
      to macrophage killing.
AB  - Previous studies suggested that the persistence in eukaryotic cells of a
      Bordetella bronchiseptica mutant carrying an insertion in the locus encoding the
      response regulator RisAS is impaired. This suggested that ris-dependent products
      are required for the intracellular survival of bacteria. In this study we
      demonstrate that ris-regulated products play a role in B. bronchiseptica
      resistance against both phagosomal acidification and reactive oxygen
      intermediates.

PMID- 11470359
TI  - Roles of superoxide dismutase and catalase of Staphylococcus xylosus in the
      inhibition of linoleic acid oxidation.
AB  - Staphylococcus xylosus used as starter culture in sausages decreases the level of
      volatile organic compounds arising from lipid oxidation and so contributes to the
      aroma by avoiding rancidity. The aim of this study was to characterize the roles
      of catalase and superoxide dismutase (SOD) in the inhibition of free fatty acid
      oxidation by comparing antioxidant capacity of the S. xylosus wild-type strain
      with those of the katA mutant and the sod mutant. Antioxidant capacity was
      determined by measuring the volatile organic compounds and the conjugated diene
      hydroperoxides arising from linoleic acid oxidation. The three strains inhibited
      the oxidation of linoleic acid. However, the katA mutant, and especially the sod
      mutant, had less antioxidant capacity than the S. xylosus wild-type strain. Thus
      both catalase and SOD of S. xylosus contributed to the inhibition of lipid
      oxidation.

PMID- 11470360
TI  - On surrogate methods for detecting lateral gene transfer.
AB  - Surrogate methods for detecting lateral gene transfer are those that do not
      require inference of phylogenetic trees. Herein I apply four such methods to
      identify open reading frames (ORFs) in the genome of Escherichia coli K12 that
      may have arisen by lateral gene transfer. Only two of these methods detect the
      same ORFs more frequently than expected by chance, whereas several intersections
      contain many fewer ORFs than expected. Each of the four methods detects a
      different non-random set of ORFs. The methods may detect lateral ORFs of
      different relative ages; testing this hypothesis will require rigorous inference
      of trees.

PMID- 11470361
TI  - The Aspergillus nidulans carnitine carrier encoded by the acuH gene is
      exclusively located in the mitochondria.
AB  - The location of the Aspergillus nidulans carnitine/acyl-carnitine carrier (ACUH)
      was studied. ACUH with a His-tag at its N-terminus was over-expressed in
      Escherichia coli and purified by Ni(2+) affinity chromatography. The purified
      protein was utilised to raise polyclonal antibodies which were characterised by
      Western blotting. For localisation studies A. nidulans T1 strain, that contains
      the acuH gene under control of the strong promoter alcA(p), was derived. Results
      obtained demonstrate the exclusively mitochondrial localisation of ACUH and
      therefore exclude the targeting of the acuH gene product to the peroxisomal
      membrane.

PMID- 11470362
TI  - Potential roles for the glnB and ntrYX genes in Azospirillum brasilense.
AB  - Three Azospirillum brasilense mutants constitutive for nitrogen fixation (Nif(C))
      in the presence of NH4(+) and deficient in nitrate-dependent growth were used as
      tools to define the roles of the glnB and ntrYX genes in this organism. Mutant
      HM14 was complemented for nitrate-dependent growth and NH4(+) regulation of
      nitrogenase by plasmid pL46 which contains the ntrYX genes of A. brasilense.
      Mutant HM26 was restored for NH4(+) regulation and nitrate-dependent growth by
      plasmid pJC1, carrying the A. brasilense glnB gene expressed from a constitutive
      promoter. Mutant HM053, on the other hand, was not complemented for NH4(+)
      regulation of nitrogenase and nitrate-dependent growth by both plasmids pJCI and
      pL46. The levels and control of glutamine synthetase activity of all mutants were
      not affected by both plasmids pL46 (ntrYX) and pJC1 (glnB). These results support
      the characterization of strains HM14 as an ntrYX mutant and strain HM26 as a glnB
      mutant and the involvement of ntrYX and glnB in the regulation of the general
      nitrogen metabolism in A. brasilense.

PMID- 11470363
TI  - Antibiotic resistance and genotypic characterization by PFGE of clinical and
      environmental isolates of enterococci.
AB  - Fifty-four Enterococcus faecalis and 20 Enterococcus faecium isolates from
      clinical and non-human sources in Rome, Italy, were characterized by antibiotic
      resistance and pulsed field gel electrophoresis (PFGE). Resistance to vancomycin,
      teicoplanin, ampicillin, and ciprofloxacin was more frequent in E. faecium than
      in E. faecalis, whereas high-level resistance to aminoglycoside was found
      primarily in E. faecalis. Multi-resistance was found primarily among clinical
      isolates, but was also observed among environmental isolates. Common genotypes
      shared among clinical and environmental isolates were observed, however, the
      majority of isolates occurred as unique, source-specific clones. Several PFGE
      types were associated with shared features in their antibiotic resistance
      patterns; evidences of clonal spread between and within wards were also noted.
      This is the first report indicating clonal relatedness between human and
      environmental enterococci isolated in Italy.

PMID- 11470364
TI  - A physical map of the megaplasmid pHG1, one of three genomic replicons in
      Ralstonia eutropha H16.
AB  - We have used pulsed field gel electrophoresis and megabase DNA techniques to
      investigate the basic genomic organization of Ralstonia eutropha H16, and to
      construct a physical map of its indigenous megaplasmid pHG1. This Gram-negative,
      soil-dwelling bacterium is a facultative chemolithoautotroph and a denitrifier.
      In the absence of organic substrates it can grow on H2 as its sole energy source
      and CO2 as its sole source of carbon. Under anaerobic conditions it can utilize
      nitrate as a terminal electron acceptor, whereby dinitrogen is released.
      Essential genetic determinants of the enzyme systems responsible for these
      metabolic processes are linked to the 0.44-Mb conjugative megaplasmid pHG1. Aside
      from pHG1, the genome of R. eutropha H16 is comprised of two circular chromosomes
      measuring 4.1 and 2.9 Mb, adding up to a total genome size of 7.1 Mb. An
      estimated five copies of rDNA are distributed on the two chromosomes. A
      macrorestriction map of pHG1 was derived for the endonucleases DraI and XbaI.
      Hybridization studies showed that genes for anaerobic metabolism are located on
      all three genomic replicons.

PMID- 11470365
TI  - Use of a green fluorescent protein gene as a reporter in Zymomonas mobilis and
      Halomonas elongata.
AB  - We investigated the applicability of the green fluorescent protein of Aequorea
      victoria as a reporter for gene expression in the strictly fermentative Gram
      negative ethanologenic bacterium Zymomonas mobilis and in the moderately
      halophilic bacterium Halomonas elongata. We have succeeded to express a mutated
      gene of green fluorescent protein under the control of different promoters in Z.
      mobilis and H. elongata grown under various glucose or salt concentrations,
      respectively. Our results demonstrate that gfp can serve as an easily assayable
      reporter gene in both organisms. Maximum fluorescence was obtained in Z. mobilis
      grown aerobically and in H. elongata grown under elevated salt concentration in
      solid medium. For both bacteria the fluorescence obtained was higher when the gfp
      gene was placed under the control of a native promoter.

PMID- 11470366
TI  - In vitro reconstruction of the biosynthetic pathway of peptidoglycan cytoplasmic
      precursor in Pseudomonas aeruginosa.
AB  - Bacterial peptidoglycan is the cell wall component responsible for maintaining
      cell integrity against osmotic pressure. Biosynthesis of the cytoplasmic
      precursor UDP-N-acetylmuramyl pentapeptide is catalyzed by the Mur enzymes.
      Genomic analysis of the three regions encoding Mur proteins was achieved. We have
      cloned and over-expressed the murA, -B, -D, -E and -F genes of Pseudomonas
      aeruginosa in pET expression system by adding a His-Tag to the C-termini of the
      proteins. Mur proteins were purified to homogeneity by a single chromatographic
      step on affinity nickel columns. Protein identities were verified through N
      terminal sequencing. Enzyme activity was proved by the identification of the
      pathway's final product.

PMID- 11470367
TI  - Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and
      gene association with insertion sequence ISEcp1.
AB  - Six non-clonally related enterobacterial isolates producing a same extended
      spectrum beta-lactamase CTX-M-15 were isolated in 1999 from patients hospitalized
      in a New Delhi hospital. CTX-M-15 differed from CTX-M-3 by an asparagine to
      glycine substitution in position ABL238. Its gene was located on large plasmids
      varying in size. In each case, a same insertion sequence ISEcp1 was identified
      upstream of the 5' end of bla(CTX-M-15). Typical -35 and -10 promoter sequences
      of Enterobacteriaceae were identified in the 3' end of ISEcp1. The location of
      ISEcp1 upstream of plasmid-mediated CTX-M-type beta-lactamase genes may
      contribute to their spread or/and their expression.

PMID- 11470368
TI  - Chloride channel antagonists perturb growth and morphology of Neurospora crassa.
AB  - The chloride channel antagonists anthracene-9-carboxylic acid, ethacrynic acid
      and niflumic acid were found to be fungistatic and morphogenic when tested
      against the ascomycete Neurospora crassa. Potency increased with decreasing pH,
      suggesting that the protonated forms of the compounds were active. Niflumic acid
      produced the most pronounced growth aberrations which may reflect an ability to
      acidify the cytoplasm and block the plasma membrane anion channel of N. crassa.

PMID- 11470369
TI  - Construction of an efficient amylolytic industrial yeast strain containing DNA
      exclusively derived from yeast.
AB  - An amylolytic industrial yeast strain of Saccharomyces cerevisiae containing the
      Schwanniomyces occidentalis SWA2 amylase gene was generated. The new strain
      contains DNA derived exclusively from yeast and expresses a high starch
      hydrolyzing activity. Yeast transformation was carried out by an integrative
      process targeted to a dispensable upstream region of the ILV2 locus, which
      determines sulfometuron resistance. The SWA2 enzyme was constitutively expressed
      under the ADH1 promoter. The growth, substrate utilization and fermentative
      capacity of this organism are described.

PMID- 11470370
TI  - Antifungal activity of three spermidine conjugates.
AB  - Three tri-substituted spermidines, di-p-coumaroyl-caffeoylspermidine, tri
      caffeoylspermidine and tri-p-coumaroylspermidine, isolated from pollen of Quercus
      alba, were examined for antifungal activity. Both di-p-coumaroyl
      caffeoylspermidine and tri-p-coumaroylspermidine reduced mycelial growth of the
      oat leaf stripe pathogen, Pyrenophora avenae and reduced powdery mildew (Blumeria
      graminis f. sp. hordei) infection of barley seedlings when applied as a post
      inoculation treatment. When used as a pre-inoculation treatment, only di-p
      coumaroyl-caffeoylspermidine reduced powdery mildew infection significantly.
      Growth of P. avenae in the presence of 100 microM di-p-coumaroyl
      caffeoylspermidine reduced activity of S-adenosylmethionine decarboxylase
      (AdoMetDC), and led to a reduction in the incorporation of labelled ornithine
      into spermidine. The other two spermidine conjugates increased AdoMetDC activity
      and the flux label from ornithine into spermine in P. avenae significantly.

PMID- 11470371
TI  - Heavy metals have different effects on mycelial morphology of Achlya bisexualis
      as determined by fractal geometry.
AB  - The morphological response, as measured by changes to mycelial area, radial
      extension and border fractal dimension, of the oomycete Achlya bisexualis to Cu,
      Co, Hg, Zn and Cd at concentrations of between 0.05 and 3 mM is described. All of
      the metals decreased mycelial area and radial extension. Border fractal dimension
      increased in the presence of Cu, Co and Hg with individual hyphae extending out
      beyond the mycelial margin. In the presence of 3 mM Hg these hyphae displayed
      spiral growth. Zn and Cd had no effect on border fractal dimension. We suggest
      that all of the metals slow growth and that Cu, Co and Hg may also disrupt the
      relationship between tip growth and branching at the edge of the mycelium.

PMID- 11470372
TI  - Isolation and characterization of Mn(III) tartrate from Phanerochaete
      chrysosporium culture broth.
AB  - High initial Mn(II) concentration results in accumulation of a Mn(III) tartrate
      complex in the growth medium of Phanerochaete chrysosporium. Since Mn(III) is the
      major oxidant in ligninolysis by manganese peroxidase, the role of accumulated
      complex should not be neglected when degradation experiments by a crude culture
      filtrate are performed. To study the Mn(III) complex oxidative potential it was
      isolated by absorption to polyamide followed by desorption with an alkaline
      methanol solution. High performance liquid chromatography analysis and atomic
      absorption spectroscopy confirmed that the isolate was Mn(III) tartrate.
      Oxidation of 2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonate) was used for
      testing the temperature and pH stability of the isolate that also intensively
      oxidized 2,6-dimethoxyphenol. In comparison with the non-isolated complex in the
      culture filtrate, the isolate showed increased temperature and pH stability. The
      oxidative potential of the isolated Mn(III) tartrate was additionally tested by
      decolorization of the synthetic dye Indigo carmine.

PMID- 11470373
TI  - Differential activities of the SoxR protein of Escherichia coli: SoxS is not
      required for gene activation under iron deprivation.
AB  - When Escherichia coli cells are under superoxide stress, proteins SoxR and SoxS,
      acting sequentially, control the expression of a set of repair and defense genes.
      One of these genes, fumC, encoding fumarase C, was reported to be also activated
      by iron deprivation in a soxRS-dependent manner. However, the same condition
      failed to induce the expression of a soxS'::lacZ fusion. The expression of acnA
      (aconitase A) is also activated by SoxR alone when under iron deprivation, but
      not of sodA (Mn-superoxide-dismutase). SoxR completely inhibited the migration of
      a DNA fragment containing the promoter region of fumC, in gel-shift experiments.
      SoxR might bind to a different region than SoxS within the fumC promoter, or an
      unknown intermediate other than SoxS might be acting. It is possible that the
      regulatory role of SoxR is more complex than previously considered.

PMID- 11470374
TI  - The Caulobacter crescentus outer membrane protein Omp58 (RsaF) is not required
      for paracrystalline S-layer secretion.
AB  - To identify the outer membrane protein component of the Caulobacter crescentus
      CB2 surface-layer export machinery we used the Serratia marcescens LipD protein
      to find homologs in the CB2 genome. From two homologous sequences found, one
      encodes a putative OMP with a predicted molecular mass of 57.5 kDa, termed Omp58
      (formerly RsaF). Comparison of membrane protein profiles revealed a protein with
      an appropriate molecular mass present in wild-type, but not CB2 omp58::kanamycin,
      a mutant strain with an inactivated omp58 gene. Disruption of omp58 did not
      affect surface-layer production, suggesting that Omp58 is not involved in surface
      layer protein secretion and, thus, may not be the outer membrane protein
      component of the C. crescentus surface-layer export system.

PMID- 11470375
TI  - Purification and characterisation of a serine peptidase from the marine
      psychrophile strain PA-43.
AB  - An extracellular serine peptidase, purified from the culture supernatant of the
      sub-Arctic psychrophilic bacterium strain PA-43, is monomeric, with a relative
      molecular mass of 76000, and an unusually low pI of 3.8. The peptidase is active
      towards N-succinyl AAPF p-nitroanilide and N-succinyl AAPL p-nitroanilide,
      indicating a chymotrypsin-like substrate specificity. It is inhibited by the
      serine peptidase inactivator phenylmethylsulfonyl fluoride, but not by EDTA or
      EGTA, suggesting that added metal ions are not necessary for activity. The enzyme
      is most active at pH 8.3 and at 55-60 degrees C, although it is unstable at 60
      degrees C. It is nevertheless remarkably stable for an enzyme from a
      psychrophilic microorganism, remaining active after 1 week at 20 degrees C and
      after five freeze-thaw cycles. Comparison of the N-terminal 40 amino acid
      residues with other archived sequences revealed highest similarity to the
      alkaline serine protease (aprx) from Bacillus subtilis.

PMID- 11470376
TI  - Effect of HEPES buffer systems upon the pH, growth and survival of Mycoplasma
      mycoides subsp. mycoides small colony (MmmSC) vaccine cultures.
AB  - The use of a buffer system based on N-[2-hydroxyethyl]piperazine-N'-[2
      ethanesulfonic acid] (HEPES), in conjunction with standard Gourlay's culture
      medium was investigated for the growth and maintenance of Mycoplasma mycoides
      subsp. mycoides SC vaccine strain T(1)44. When the initial pH of the culture
      medium was adjusted to 8.0, 0.075 M HEPES-NaOH was found to be sufficient to
      prevent the pH falling below 7.1 at any stage during the growth cycle, even in
      the presence of 0.5% glucose. Compared to growth in standard unbuffered Gourlay's
      medium, the final culture titre was found to be one log(10) higher, at 10(11)
      colour changing units (CCU) per ml, and considerably extended culture survival
      was observed at 37 degrees C. The titre remained above 10(10) CCU ml(-1) for 4
      days, and above 10(8) CCU ml(-1) in excess of 1 month. After 4 month's storage at
      37 degrees C the titre had fallen to 5x10(4) CCU ml(-1). In contrast, no viable
      bacteria could be detected in standard unbuffered medium 3 days after the onset
      of stationary phase, at which point the pH had dropped to 5.4. No significant
      difference in growth rate between the two media was observed. Adoption of a HEPES
      NaOH buffer system by African vaccine manufacturers should require minimal
      changes to current formulations and procedures, and should enhance both the final
      titre and thermostability of freeze-dried and liquid broth vaccines against
      contagious bovine pleuropneumonia (CBPP).

PMID- 11470378
TI  - Repeated prenatal corticosteroid administration delays astrocyte and capillary
      tight junction maturation in fetal sheep.
AB  - Glucocorticoids are powerful regulators of cell differentiation and maturation.
      Their synthetic counterparts, the corticosteroids, are used widely in obstetric
      practice to enhance fetal lung maturation in cases of threatened preterm birth.
      Here we examined the effects of repeated corticosteroid administration on
      astrocyte and capillary tight junction development in the fetal sheep brain,
      selecting the corpus callosum for analysis. Pregnant ewes were given saline or
      betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation. Lambs were
      delivered at term, terminally anaesthetized and transcardially perfused.
      Transverse semi-thin sections of the corpus callosum were cut and immuno-stained
      with antibody against glial fibrillary acidic protein (GFAP). Ultra-thin sections
      were examined in the electron microscope. The percentage area of GFAP staining
      was reduced in the corticosteroid-treated group compared to control (5.2 vs.
      8.7%, P<0.05). The expression of GFAP in peri-capillary and parenchymal
      astrocytes was also reduced compared to control (peri-capillary: 3.0 vs. 9.5
      microm2; parenchymal: 14.6 vs. 29.4 microm2, P<0.05). Furthermore, capillary
      tight junction maturation was delayed compared to control. Immature 'type II'
      junctions were more common in the corticosteroid-treated group (63 vs. 22%,
      P<0.05), whereas more mature 'type III' junctions were less common (27 vs. 65%,
      P<0.05). Our data suggest that repeated corticosteroids delay both astrocyte and
      capillary tight junction maturation. The implications for clinical practice are
      as yet unknown.

PMID- 11470379
TI  - Postnatal development of cholinergic system in mouse basal forebrain:
      acetylcholinesterase histochemistry and choline-acetyltransferase
      immunoreactivity.
AB  - The distribution of acetylcholinesterase histochemistry and choline-O
      acetyltransferase immunohistochemistry in the basal forebrain was studied in
      newborn mice (P0) and until 60 days of postnatal life (P60). A weak
      acetylcholinesterase activity was found at P0 and P2 in the anterior and
      intermediate parts of the basal forebrain, and higher in the posterior region.
      The intensity of labeling, neuronal size and dendritic growth seems to increase
      progressively in all regions of basal forebrain from P4 to P10. The AChE+ cell
      count shows that in the anterior portion of the magnocellular basal nucleus the
      number of cells does not vary significantly from birth to the second month of
      postnatal life. However, in the intermediate and posterior portions of the
      nucleus the mean number of labeled cells increases significantly from birth to
      the end of the second week of postnatal life (P13). The choline-acetyltransferase
      immunoreactivity appears only detectable at the end of the first week (P6) as a
      slight immunoreaction, which increases progressively in intensity at P8, and at
      P10 seems to attain the same intensity of labeling found at P60. These results
      seem to indicate that the acetylcholinesterase could have a non-classic
      cholinergic role in the first stages of postnatal development, acting as a growth
      and cellular differentiation factor.

PMID- 11470380
TI  - Redistribution and increased specificity of GABA(B) receptors during development
      of the rostral nucleus of the solitary tract.
AB  - Recent results show that there is an abundance of gamma-aminobutyric acid (GABA)
      before GABAergic synapses have formed in the gustatory zone of the nucleus of the
      solitary tract. These results suggest that a non-synaptic, developmental function
      may exist for GABA prior to synaptogenesis. However, GABA exerts its
      physiological effect via its receptors, the development of which is a largely
      unknown process. The developmental expression of one of the GABA receptors in the
      young nucleus of the solitary tract is the focus of this study. The development
      of GABA(B) receptors was investigated by light and electron microscopy. The
      results suggest that before the development of GABAergic synapses, GABA(B)
      receptors are diffusely distributed. When GABAergic synapses form, the receptors
      become clustered. Quantitative postembedding immunohistochemical studies at the
      electron microscopic level show that extrasynaptic labeling for GABA(B) receptors
      decreases during development, but synaptic labeling increases. Increased
      specificity of neurotransmitter receptors at synapses has been shown in other
      systems during development, including other central nervous system structures,
      but this may be the first demonstration of the phenomenon using quantitative
      electron microscopy.

PMID- 11470381
TI  - Dendrite development and target innervation of displaced retinal ganglion cells
      of the chick (Gallus gallus).
AB  - The avian accessory optic system (AOS) processes visual signals of translational
      and rotational flowfields resulting from self-motion. It has been investigated
      extensively with physiological methods and, because of its anatomical distinction
      from other retinofugal projections, is well suited for the investigation of
      dendritic differentiation and axonal pathfinding. Displaced retinal ganglion
      cells (dRGC) constitute the retinal origin of the AOS. Since little is known
      about the time course of the development of this projection, we studied the
      dendritic differentiation of dRGC, their innervation of the nucleus of the basal
      optic root (nBOR) and the histological development of this target area. dRGC,
      visualized by retrograde 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine
      perchlorate labeling, migrated into the inner nuclear layer of the retina and
      subsequently developed their characteristic dendritic morphology between E9 and
      E14. At this stage, dendrites were unistratified in the inner plexiform layer and
      displayed characteristic branches with 45-90 degrees angles. The frequency of
      dendritic branches increased from an average of 44 branches per cell at E9 to an
      average of 155 at E15. This phase was followed by a period of dendritic pruning,
      E15-E17, where a large number of small branches were eliminated. At the time of
      hatching, dRGC were morphologically mature with mean dendritic field sizes of
      0.28 mm2 and an average of 108 dendritic branches per cell. Retinal innervation
      of the nBOR occurred between E8 and E11, and tracer injections at later stages
      revealed no further changes. In addition to the predominant contralateral
      projection, we have also described a connection to the ipsilateral nBOR. This
      ipsilateral pathway persisted at least to juvenile stages (P14). The histological
      development of the nBOR proceeded such that calretinin-immunoreactive neurons
      were observed from E10 onwards and morphologically described cell types evolved
      after E12.

PMID- 11470382
TI  - Synaptic development in semi-dissociated cultures of rat retina.
AB  - Cultured neurons provide a simpler and more accessible environment to study the
      synaptic physiology. However, it is not clear if development of synapses in
      culture is similar to that in the in vivo condition. We studied the developmental
      sequence and morphological differentiation of chemical synapses in semi
      dissociated rat retinal cultures that consisted of dissociated neurons as well as
      undissociated retinal aggregates. Synapses were quantified by synaptophysin
      immunoreactive puncta. During second week of in vitro development the average
      number of chemical synapses on the cell body decreased while that on the neurites
      increased significantly. Conventional synapses appeared both in aggregate and in
      dissociated neurons, with the developmental profile similar to that reported for
      in vivo retina. In contrast, the development of ribbon synapses was adversely
      affected by the in vitro microenvironment as suggested by following observations.
      The ribbon synapses were more frequently found in aggregate than in dissociated
      neurons, and were not associated with dyadic or triadic synaptic arrangement. The
      photoreceptor ribbons did not contact a postsynaptic process while bipolar
      ribbons made single (monadic) synapses. Further, photoreceptor ribbons in
      dissociated neurons were late to form and took more time to mature as compared to
      those in the aggregate cultures. Most of the rod bipolar cells, identified by
      their immunoreactivity to protein kinase C (PKC), had three or more neurites.
      Unlike in the in vivo retina, the dissociated rod bipolar cells did not show any
      PKC immunoreactive varicosities, suggesting that they failed to develop a well
      differentiated synaptic terminal. Interestingly, we did not find any parvalbumin
      positive AII amacrine cells that are normally postsynaptic to rod bipolar cells.
      These results show that the conventional synapses of retina, which are similar to
      chemical synapses in other parts of the brain, develop normally both in aggregate
      and dissociated neurons. However, the highly specialized ribbon synapses have
      more stringent developmental requirements, and their normal development may
      require the presence of postsynaptic neurons in their close vicinity.

PMID- 11470383
TI  - SODA (severity of dyspepsia assessment): a new effective outcome measure for
      dyspepsia-related health.
AB  - The aim of this research was to develop and evaluate an instrument for measuring
      dyspepsia-related health to serve as the primary outcome measure for randomized
      clinical trials. Building on our previous work we developed SODA (Severity of
      Dyspepsia Assessment), a multidimensional dyspepsia measure. We evaluated SODA by
      administering it at enrollment and seven follow-up visits to 98 patients with
      dyspepsia who were randomized to a 6-week course of omeprazole versus placebo and
      followed over 1 year. The mean age was 53 years, and six patients (6%) were
      women. Median Cronbach's alpha reliability estimates over the eight visits for
      the SODA Pain Intensity, Non-Pain Symptoms, and Satisfaction scales were 0.97,
      0.90, and 0.92, respectively. The mean change scores for all three scales
      discriminated between patients who reported they were improved versus those who
      were unchanged, providing evidence of validity. The effect sizes for the Pain
      Intensity (.98) and Satisfaction (.87) scales were large, providing evidence for
      responsiveness. The effect size for the Non-Pain Symptoms scale was small (.24),
      indicating lower responsiveness in this study sample. SODA is a new, effective
      instrument for measuring dyspepsia-related health. SODA is multidimensional and
      responsive to clinically meaningful change with demonstrated reliability and
      validity.

PMID- 11470384
TI  - A prognostic index for 30-day mortality after stroke.
AB  - The objective of this study was to develop a simplified scoring system to predict
      30-day mortality in patients with acute ischemic stroke. A retrospective cohort
      study was performed in a tertiary referral hospital in the Hunter Region of
      Australia. A prognostic index was created by assigning points to the variables in
      a Cox model. The index included impaired consciousness (5 points), dysphagia (3
      points), urinary incontinence (4 points), admission body temperature higher than
      36.5 degrees C (2 points), and hyperglycemia without a clinical history of
      diabetes (2 points). A score of 11 or more defined a high-risk group. The index
      achieved a sensitivity, specificity, and positive predictive value of 68%, 98%
      and 75%, respectively, in the derivation sample and 57%, 97% and 68%,
      respectively, in the validation sample. The results provide a simple risk
      stratification instrument for clinical research and practice. Further evaluation
      of the model in a prospective cohort is warranted

PMID- 11470385
TI  - Internal validation of predictive models: efficiency of some procedures for
      logistic regression analysis.
AB  - The performance of a predictive model is overestimated when simply determined on
      the sample of subjects that was used to construct the model. Several internal
      validation methods are available that aim to provide a more accurate estimate of
      model performance in new subjects. We evaluated several variants of split-sample,
      cross-validation and bootstrapping methods with a logistic regression model that
      included eight predictors for 30-day mortality after an acute myocardial
      infarction. Random samples with a size between n = 572 and n = 9165 were drawn
      from a large data set (GUSTO-I; n = 40,830; 2851 deaths) to reflect modeling in
      data sets with between 5 and 80 events per variable. Independent performance was
      determined on the remaining subjects. Performance measures included
      discriminative ability, calibration and overall accuracy. We found that split
      sample analyses gave overly pessimistic estimates of performance, with large
      variability. Cross-validation on 10% of the sample had low bias and low
      variability, but was not suitable for all performance measures. Internal validity
      could best be estimated with bootstrapping, which provided stable estimates with
      low bias. We conclude that split-sample validation is inefficient, and recommend
      bootstrapping for estimation of internal validity of a predictive logistic
      regression model.

PMID- 11470386
TI  - Impact of different definitions on estimates of accuracy of the diagnosis data in
      a clinical database.
AB  - Computerized medical databases are increasingly used for research. The influence
      of different definitions of the accuracy of matching on the estimated accuracy of
      diagnosis data was assessed in a database of visits to a public pediatric clinic.
      Differences between definitions involved 1) unit of analysis, 2) number of
      diagnoses required to match per visit, and/or 3) whether database contents are
      required to match the medical record or medical record contents are required to
      be matched in the database. Overall, 90% of diagnoses in the database (391/435)
      were accurately coded relative to the medical record. Alternatively, 77% of
      diagnoses listed in the medical record (391/506) were accurately coded in the
      database. When individual visits were used as the unit of analysis, estimates of
      accuracy using six definitions ranged from 65% to 92%. The most appropriate
      definition to use for estimating accuracy of diagnosis data likely depends on the
      purpose of the study. Use of two or more such definitions may enhance portrayal
      of the accuracy of diagnosis data.

PMID- 11470387
TI  - Generalizability of trial results based on randomized versus nonrandomized
      allocation of OME infants to ventilation tubes or watchful waiting.
AB  - The objective was to study the generalizability of trial results by comparing
      randomized patients to eligible but nonrandomized patients who received the same
      management. Implementation of trial results is only justifiable when the results
      can be generalized to the total domain population. The design was a multicentre
      randomized controlled trial on the effect of early screening and treatment with
      ventilation tubes on infants with otitis media with effusion. Randomized (n =
      187) and nonrandomized eligible patients (n = 133) were followed up. The study
      population comprised children who were detected by auditory screening at the age
      of 9-12 months and who were subsequently diagnosed with persistent bilateral
      otitis media with effusion for 4-6 months. A significant difference was found in
      the distribution of some prognostic factors: more randomized children had older
      siblings, did not attend day care and had mothers with a lower educational level
      than the nonrandomized children. These factors, however, did not modify the
      outcome. No differences were found in mean hearing levels between the randomized
      and nonrandomized children: in both the randomized and nonrandomized children
      ventilation tubes improved the hearing level, especially after 6 months. However,
      in the long term (12 months), the hearing levels were equal again. The results of
      the randomized and nonrandomized patients were comparable. The results of this
      trial appear to be generalizable to the total domain population. The procedure of
      following up both randomized and nonrandomized patients is recommended when there
      is concern about selective participation and reduced generalizability.

PMID- 11470388
TI  - Institutionalization in the elderly: the role of chronic diseases and dementia.
      Cross-sectional and longitudinal data from a population-based study.
AB  - A population-based study of 1810 persons, aged 75+, was investigated to evaluate
      the role of dementia and other chronic diseases as determinants of
      institutionalization in the elderly. The study population was examined at
      baseline and after a 3-year interval. After adjustment for sociodemographic
      characteristics, functional dependence, dementia, cerebrovascular disease and hip
      fracture were associated with living in an institution at baseline. Additionally,
      functional dependence, hip fracture and dementia were also associated with moving
      to an institution during the 3-year follow-up. In a similar analysis, including
      only nondemented subjects, the Mini-Mental State Examination emerged as one of
      the strongest determinants. The population attributable risk percentage of
      institutionalization during the 3-year follow-up due to dementia was 61%. This
      study confirms that dementia and cognitive impairment are the main contributors
      to institutionalization in the elderly, independently of their sociodemographic
      status, social network, or functional status.

PMID- 11470389
TI  - Cause-specific mortality in a cohort of patients with diabetes mellitus: a
      population-based study in Sweden.
AB  - A cohort of patients with diabetes mellitus hospitalised in Sweden from 1965 to
      1983 was followed up until 1989, by linkages of population-based registers.
      Standardised mortality ratios (SMR), adjusted for confounding variables, and 95%
      confidence intervals (CIs) were calculated. After exclusion of the first year of
      follow-up (to reduce the effect of selection bias), the cohort consisted of
      144,427 patients, of whom 92,248 patients died during follow-up. The SMR for all
      causes of death combined was 2.62 (95% CI 2.58-2.67) among men and 3.23 (95% CI
      3.18-3.28) among women. The excess mortality was still evident 20 years after
      first hospitalisation, but became less marked with longer follow-up time.
      Patients with presumably insulin-dependent diabetes mellitus (IDDM) had the
      highest SMRs (10.2; CI 9.5-11.0); however, there was a significant (34%)
      improvement over time in their mortality risk. We conclude that excess mortality
      persisted throughout all calendar periods and at all ages, indicating the need
      for health care prevention measures.

PMID- 11470390
TI  - Congestive heart failure and outpatient risk of venous thromboembolism: a
      retrospective, case-control study.
AB  - Although CHF has been considered a risk factor for venous thromboembolism, this
      has not been directly studied. We hypothesized that congestive heart failure
      would increase the risk of venous thromboembolism in an outpatient population,
      and that this risk would increase as patients' ventricular function worsened. We
      conducted a case-control study to examine whether CHF due to left ventricular
      dysfunction was an independent risk factor for acute venous thromboembolism in
      outpatients, once established risk factors such as recent surgery and prior
      venous thromboembolism are taken into account. We reviewed 106 cases of DVT and
      603 controls, admitted for diabetes mellitus or infection, matched for month of
      admission at a VA hospital. Assignment of a diagnosis of venous thromboembolism
      required a definitive test, as did classification as CHF. In a logistic
      regression model CHF was an independent predictor of venous thromboembolism. A
      second logistic regression model showed that the risk of venous thromboembolism
      increased as the ejection fraction (EF) decreased, with an EF < 20 associated
      with a venous thromboembolism OR of 38.3 (95% CI 9.6, 152.5). CHF is an
      independent risk factor for venous thromboembolism, and the risk increases
      markedly as the EF decreases. These results support the use of anticoagulation in
      selected patients with CHF.

PMID- 11470391
TI  - Comparison of weight-for-height indices as a measure of adiposity and
      cardiovascular risk from childhood to young adulthood: the Bogalusa heart study.
AB  - The development of obesity in childhood is considered a major determinant of
      cardiovascular risk. Currently the body mass index (BMI = weight/height(2)) is
      widely used as a measure of obesity. However, since BMI is associated with height
      during childhood, a weight for height index (weight/height(p)) that is
      independent of height is thought to be more appropriate. Therefore, to compare
      the utility of such weight/height(p) index with BMI in assessing adiposity and
      its relation to cardiovascular risk variable data from the Bogalusa Heart Study
      participants aged 6 months to 21 years were examined. A total of 31,796
      observations on 12,827 subjects was used in the data analysis. Study variables
      include height, weight, subscapular and triceps skinfolds, blood pressure, serum
      lipids and lipoproteins, and plasma glucose and insulin. The optimal exponential
      for the weight/height(p) index started from 2.42 in the 6 month olds, decreased
      to 1.86 in 2 to 3 year olds, increased to 3.29 among 10 to 11 year olds, and then
      decreased to 2.15 in the 20 to 21 year olds. The BMI showed slightly higher
      correlations than weight/height(p) index with subscapular skinfold in children.
      Both in children and young adults BMI also showed a slightly higher correlation
      with other cardiovascular risk factor variables regardless of age-race-sex
      groups. These results indicate that weight/height(p) index is not superior to BMI
      as an indicator of adiposity and related cardiovascular risk factors during
      childhood.

PMID- 11470392
TI  - Coffee consumption and serum aminotransferases in middle-aged Japanese men.
AB  - We investigated the relation between coffee drinking and serum aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) concentrations among
      7313 Japanese men receiving a health examination, excluding former alcohol
      drinkers and men with a history of chronic liver disease. Serum AST > 40 and/or
      ALT > 40 U/L was defined as liver inflammation. Adjustment was made for alcohol
      use, smoking, body mass index, serum marker for hepatitis virus infection, and
      other possible confounders. Adjusted odds ratios of liver inflammation were 1.00
      (reference), 0.80, 0.69, and 0.61 for men drinking < 1, 1-2, 3-4, and > or = 5
      cups of coffee daily, respectively. Among 6898 men without liver inflammation,
      serum AST and ALT were inversely associated with coffee consumption, and alcohol
      related rise in AST was attenuated with coffee drinking. These findings suggest
      coffee may have an effect of suppressing the rise of serum aminotransferase,
      partly by inhibiting the alcohol-related elevation. Studies regarding biological
      mechanism are warranted.

PMID- 11470393
TI  - Detecting the effect of medical care on mortality.
AB  - OBJECTIVES: To demonstrate an important limitation of empirical tests of the
      proposition that medical care has contributed to long-term declines in mortality.
      Quasi-experiments cannot detect the effect of care that sustain, rather than
      change, a downward trajectory. We demonstrate this limitation by testing two
      hypotheses. One is that isolation of patients and antibiotic treatment coincided
      with declines in tuberculosis (TB) mortality in Massachusetts between 1850 and
      1950. Another is that the introduction of Medicare in the 1960s increased life
      expectancy at age 65. RESULTS: The first hypothesis is supported, for both
      patient isolation and streptomycin. The second is not. The circumstances that
      could yield such results are explored. CONCLUSIONS: Epidemiologists and
      historians should cooperate to devise methods that can resolve the issue of
      whether medical care has sustained the steady downward trend in mortality
      witnessed over the last century-and-a-half.

PMID- 11470394
TI  - Fall-risk screening test: a prospective study on predictors for falls in
      community-dwelling elderly.
AB  - This large prospective cohort study was undertaken to construct a fall-risk model
      for elderly. The emphasis of the study rests on easily measurable predictors for
      any falls and recurrent falls. The occurrence of falls among 1285 community
      dwelling elderly aged 65 years and over was followed during 1 year by means of a
      "fall calendar." Physical, cognitive, emotional and social functioning preceding
      the registration of falls were studied as potential predictors of fall-risk.
      Previous falls, visual impairment, urinary incontinence and use of
      benzodiazepines were the strongest predictors identified in the risk profile
      model for any falls (area under the curve [AUC] = 0.65), whereas previous falls,
      visual impairment, urinary incontinence and functional limitations proved to be
      the strongest predictors in the model for recurrent falls (AUC = 0.71). The
      probability of recurrent falls for subsequent scores of the screening test ranged
      from 4.7% (95% Confidence Interval [CI]: 4.0-5.4%) to 46.8% (95% CI: 43.0-50.6%).
      Our study provides a fall-risk screening test based on four easily measurable
      predictors that can be used for fall-risk stratification in community-dwelling
      elderly.

PMID- 11470395
TI  - Primary biliary cirrhosis among atomic bomb survivors in Nagasaki, Japan.
AB  - Despite rapid progress in methods for analyzing radiation effects, much remains
      to be learned about the mechanisms and processes of radiation-induced
      immunological dysfunction. Among 17,899 sera obtained from atomic bomb survivors
      in Nagasaki, Japan, sera from 484 participants who complied with a reexamination
      for alkaline phosphatase (ALP) were tested for antimitochondrial antibody (AMA)
      by indirect immunofluorescence, and autoantibodies against 2-oxo-acid
      dehydrogenase complex (2-OADC) by immunoblotting to investigate the prevalence of
      primary biliary cirrhosis (PBC). Of these 484 sera, 28 (5.8%) were seropositive
      for AMA. The 484 participants were divided into three groups according to
      distance from the hypocenter: 72 who were exposed within 1999 m (closest group),
      368 from 2000 to 5999 m (intermediate distant group), and 44 outside 6000 m
      (distant group). The positivity rates for AMA in these three groups were 6/72
      (8.3%), 22/368 (6.0%), and 0/44 (0%), respectively (P =.08). Furthermore, high
      titers ( > 1:320) of AMA were observed in 3/6 (50%) AMA-positive sera from the
      closest group, in contrast to 4/22 (18%) from the intermediate distant group,
      although there was no significant correlation between AMA titer and distance from
      the hypocenter (P =.07). Of these 28 AMA-positive sera, 11 (39%) were from
      participants who had already been diagnosed with PBC, and 25 (89%) contained
      antibodies against at least one component of 2-OADC enzymes by immunoblotting.
      Therefore, the prevalence of PBC was estimated to be at least 615 cases per
      million (792 per million women). Our results suggest that the prevalence of PBC
      in atomic bomb survivors in Nagasaki is higher than that reported for the general
      population in Japan, and a further survey of the environmental factors, including
      radiation exposure, that predispose to PBC would be needed for understanding this
      disease of unknown etiology.

PMID- 11470396
TI  - The association between exposure to a rear-end collision and future health
      complaints.
AB  - Different symptoms, together with neck pain, have been attributed to persons with
      persistent complaints after a previous motor vehicle crash (MVC) and are
      sometimes referred to as the "late whiplash syndrome." A cohort study was
      conducted to determine whether exposure to a rear-end collision, with or without
      whiplash injury, is associated with future health complaints. The results
      regarding future neck or shoulder pain have previously been described, and the
      objective of the present report was to focus on outcomes other than neck pain.
      Included in the study were persons 18 to 65 years of age and covered by traffic
      insurance at one of the largest insurance companies in Sweden. Claim reports were
      collected from the period November 1987 to April 1988. Drivers exposed to a rear
      end collision were divided into two subgroups: those with reported whiplash
      injury (n = 232) and those without reported whiplash injury (n = 204). For
      comparison, 3688 subjects who were unexposed to MVCs were selected, with
      consideration taken to the age and gender distribution in the exposed subgroups.
      The prevalence of different health complaints among the study subjects was
      estimated according to a mailed questionnaire at follow-up in 1994, 7 years after
      the rear-end collision. When exposed subjects with whiplash injury were compared
      to unexposed subjects, increased relative risks in the range of 1.6-3.7 were seen
      for headache, thoracic and low back pain, as well as for fatigue, sleep
      disturbances and ill health. No corresponding increased risks were found among
      the exposed subjects without reported whiplash injury. We conclude that rear-end
      collisions resulting in reported whiplash injuries seem to have a substantial
      impact on health complaints, even a long time after the collision. There is a
      need to identify factors that predict a non-favorable outcome in order to improve
      clinical management.

PMID- 11470397
TI  - Incidence of Reye's syndrome in France: a hospital-based survey.
AB  - At the time of the study no information was available in France about the
      incidence of Reye's Syndrome (RS) and no warnings about RS and aspirin. The
      objective was to evaluate the incidence of RS in France by a hospital-based
      study. For a period of 1 year from November 1995 to November 1996, all French
      paediatric departments were required to report any child under 15 years with
      unexplained noninflammatory encephalopathy (i.e., CDC consciousness level stage I
      or deeper with normal CSF) and a threefold (or greater) increase in serum
      aminotransferase and/or ammonia. All suspected cases were classified by a panel
      of experts as probable RS or excluded RS. In 10% of randomly selected paediatric
      departments we checked that every suspected case had been reported. Forty-six
      suspected cases were reported during the year of the survey, of which 14 were
      classified as RS. Five of these 14 cases had a metabolic disorder. Nine children
      were definitively diagnosed as having RS (i.e., an estimated incidence of RS of
      0.79/1,000,000 children, i.e., below 15/year). Eight children had been exposed to
      aspirin, four to aspirin alone and four to aspirin and acetaminophen. On the
      basis of these results the incidence of RS in France in 1996-1997 was not
      substantially different from that of countries where warning labels were already
      in use, but it was higher than in the US after 1994. This was probably due to the
      reduction in aspirin prescription in France because of warnings in Europe and the
      US and also because many cases of RS are now identified as metabolic disease. On
      the basis of these results and because the relationship between aspirin and RS
      has already been proved, public and professional warnings concerning RS on
      aspirin-containing products in cases of varicella and viral febrile illness have
      been adopted by the French Drugs Agency.

PMID- 11470398
TI  - Distinct expression of type XIII collagen in neuronal structures and other
      tissues during mouse development.
AB  - Type XIII collagen is a type II transmembrane protein found in adhesive
      structures of mature tissues. We describe here its expression and spatio-temporal
      localization during mouse fetal development. Type XIII collagen mRNAs were
      expressed at a constant rate during development, with an increase of expression
      towards birth. Strong type XIII collagen expression was detected in the central
      and peripheral nervous systems of the developing mouse fetus in mid-gestation.
      Cultured primary neurons also expressed this collagen, and it was found to
      enhance neurite outgrowth. The results suggest that type XIII collagen is a new
      member among the proteins involved in nervous system development. Strong
      expression during early development was also detected in the heart, with
      localization to cell-cell contacts and accentuation in the intercalated discs
      perinatally. During late fetal development, type XIII collagen was observed in
      many tissues, including cartilage, bone, skeletal muscle, lung, intestine and
      skin. Clear developmental shifts in expression suggest a role in endochondral
      ossification of bone and the branching morphogenesis in the lung. Notable
      structures lacking type XIII collagen were the endothelia of most blood vessels
      and the endocardium. Its initially unique staining pattern began to concentrate
      in the same adhesive structures where it exists in adult tissues, and started to
      resemble that of the beta1 integrin subunit and vinculin during late intrauterine
      development and in the perinatal period.

PMID- 11470399
TI  - Prevention of IGF-1 and TGFbeta stimulated type II collagen and decorin
      expression by bFGF and identification of IGF-1 mRNA transcripts in articular
      chondrocytes.
AB  - OBJECTIVES: the aim of this investigation was to establish whether the action of
      bFGF modulated the production of type II collagen, decorin and biglycan induced
      by IGF-1 or TGFbeta in porcine articular chondrocytes. In addition, the study
      would establish which multiple transcripts of IGF-1 were present in articular
      cartilage, and which growth factors influenced their expression. METHODS: steady
      state levels of mRNA specific for IGF-1 and matrix proteins were extracted as
      total RNA from porcine articular chondrocytes and processed for Northern blot
      analysis. High-density cell monolayers were established in the presence of serum,
      then maintained in a serum-free state for up to 7 days with increasing doses of
      either IGF-1 or TGFbeta in the presence or absence of bFGF. RESULTS: bFGF
      prevented the stimulation of type II collagen and decorin induced in the presence
      of IGF-1 or TGFbeta and up-regulated the production of biglycan in cultured
      chondrocytes without altering the gene expression of IGF-1. Four IGF-1
      transcripts were found in cultured adherent chondrocytes, approximately 77% was
      present as a major 4.7kb transcript with lower levels of 7.6 (4%), 1.3 (11%) and
      1.1 (8%) kb forms. CONCLUSIONS: bFGF acts as an antagonist for the production of
      type II collagen and decorin and also acts as a strong inducer like IGF 1 and
      TGFbeta for the expression of biglycan in porcine cultured chondrocytes. The
      apparent lack of a dose and time effect on expression of the IGF-1 gene was
      surprising and may be due to the stability of the IGF-1 message.

PMID- 11470400
TI  - On (GGLGY) synthetic repeating sequences of lamprin and analogous sequences.
AB  - The repetitive sequence GGLGY was found in lamprin, the most important matrix
      protein of lamprey annular cartilage by Keeley and co-workers. Similar sequences
      appear also in other proteins, i.e. elastin, spidroin, spider minor ampullate
      silk proteins, in matrix proteins of the chorion or egg shell membrane of insects
      and others. We synthesized (GGLGY)n, n=1, 2, 6, because the sequence is repeated
      six times in the aggregated protein. The peptides were studied both in solution
      and in the solid state. Because the CD spectra were dominated by aromatic
      contribution, we synthesized GGLGF and GGLGA in order to carefully interpret the
      CD spectra. The conformational analysis suggests that all synthetic peptides do
      adopt the same secondary structure. In solution the peptides present a flexible
      conformation with a significant amount of PPII structure. In the solid state
      PPII, beta-pleated-sheets and beta-turns possibly co-exist.

PMID- 11470401
TI  - Calreticulin, PDI, Grp94 and BiP chaperone proteins are associated with retained
      COMP in pseudoachondroplasia chondrocytes.
AB  - Cartilage oligomeric matrix protein (COMP), a large pentameric glycoprotein and
      member of the thrombospondin (TSP) group of extracellular proteins, is found in
      the territorial matrix surrounding chondrocytes. More than 50 unique COMP
      mutations have been identified as causing two skeletal dysplasias:
      pseudoachondroplasia (PSACH); and multiple epiphyseal dysplasia (EDM1). Recent
      studies suggest that calcium-binding and calcium-induced protein folding differ
      between wild type and mutant proteins, and abnormal processing of the mutant COMP
      protein contributes to the characteristic enlarged lamellar appearing rER
      cisternae in PSACH and EDMI chondrocytes in vivo and in vitro. Towards the goal
      of delineating the pathogenesis of PSACH and EDM1, in-vivo PSACH growth plate and
      in-vitro PSACH chondrocytes cultured in alginate beads were examined to identify
      and localize the chaperone proteins participating in the processing of the
      retained extracellular matrix proteins in the PSACH rER. Aggrecan was localized
      to both the rER cisternae and matrix while COMP and type IX collagen were only
      found in the rER. Type II collagen was solely found in the ECM suggesting that it
      is processed and transported differently from other retained ECM proteins. Five
      chaperone proteins: BiP (Grp78); calreticulin (CRT); protein disulfide (PDI);
      ERp72; and Grp94, demonstrated immunoreactivity in the enlarged PSACH cisternae
      and the short rER channels of chondrocytes from both in-vivo and in-vitro
      samples. The chaperone proteins cluster around the electron dense material within
      the enlarged rER cisternae. CRT, PDI and GRP94 AB-gold particles appear to be
      closely associated with COMP. Immunoprecipitation and Western blot, and
      Fluorescence Resonance Energy Transfer (FRET) analyses indicate that CRT, PDI and
      GRP94 are in close proximity to normal and mutant COMP and BiP to mutant COMP.
      These results suggest that these proteins play a role in the processing and
      transport of wild type COMP in normal chondrocytes and in the retention of mutant
      COMP in PSACH chondrocytes.

PMID- 11470402
TI  - Response to Engel and Bachinger's critique of collagen denaturation as a rate
      process.

PMID- 11470404
TI  - A screen for genes required for meiosis and spore formation based on whole-genome
      expression.
AB  - BACKGROUND: Meiosis is the process by which gametes are generated with half the
      ploidy of somatic cells. This reduction is achieved by three major differences in
      chromosome behavior during meiosis as compared to mitosis: the production of
      chiasmata by recombination, the protection of centromere-proximal sister
      chromatid cohesion, and the monoorientation of sister kinetochores during meiosis
      I. Mistakes in any of these processes lead to chromosome missegregation. RESULTS:
      To identify genes involved in meiotic chromosome behavior in Saccharomyces
      cerevisiae, we deleted 301 open reading frames (ORFs) which are preferentially
      expressed in meiotic cells according to microarray gene expression data. To
      facilitate the detection of chromosome missegregation mutants, chromosome V of
      the parental strain was marked by GFP. Thirty-three ORFs were required for the
      formation of wild-type asci, eight of which were needed for proper chromosome
      segregation. One of these (MAM1) is essential for the monoorientation of sister
      kinetochores during meiosis I. Two genes (MND1 and MND2) are implicated in the
      recombination process and another two (SMA1 and SMA2) in prospore membrane
      formation. CONCLUSIONS: Reverse genetics using gene expression data is an
      effective method for identifying new genes involved in specific cellular
      processes.

PMID- 11470405
TI  - A Rho-dependent signaling pathway operating through myosin localizes beta-actin
      mRNA in fibroblasts.
AB  - BACKGROUND: The sorting of mRNA is a determinant of cell asymmetry. The cellular
      signals that direct specific RNA sequences to a particular cellular compartment
      are unknown. In fibroblasts, beta-actin mRNA has been shown to be localized
      toward the leading edge, where it plays a role in cell motility and asymmetry.
      RESULTS: We demonstrate that a signaling pathway initiated by extracellular
      receptors acting through Rho GTPase and Rho-kinase regulates this spatial aspect
      of gene expression in fibroblasts by localizing beta-actin mRNA via actomyosin
      interactions. Consistent with the role of Rho as an activator of myosin, we found
      that inhibition of myosin ATPase, myosin light chain kinase (MLCK), and the
      knockout of myosin II-B in mouse embryonic fibroblasts all inhibited beta-actin
      mRNA from localizing in response to growth factors. CONCLUSIONS: We therefore
      conclude that the sorting of beta-actin mRNA in fibroblasts requires a Rho
      mediated pathway operating through a myosin II-B-dependent step and postulate
      that polarized actin bundles direct the mRNA to the leading edge of the cell.

PMID- 11470406
TI  - Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable
      elements in the D. melanogaster germline.
AB  - BACKGROUND: The injection of double-stranded RNA (dsRNA) has been shown to induce
      a potent sequence-specific inhibition of gene function in diverse invertebrate
      and vertebrate species. The homology-dependent posttranscriptional gene silencing
      (PTGS) caused by the introduction of transgenes in plants may be mediated by
      dsRNA. The analysis of Caenorhabditis elegans mutants impaired with dsRNA
      mediated silencing and studies in plants implicate a biological role of dsRNA
      mediated silencing as a transposon-repression and antiviral mechanism. RESULTS:
      We investigated the silencing of testis-expressed Stellate genes by paralogous
      Su(Ste) tandem repeats, which are known to be involved in the maintenance of male
      fertility in Drosophila melanogaster. We found that both strands of repressor
      Su(Ste) repeats are transcribed, producing sense and antisense RNA. The Stellate
      silencing is associated with the presence of short Su(Ste) RNAs. Cotransfection
      experiments revealed that Su(Ste) dsRNA can target and eliminate Stellate
      transcripts in Drosophila cell culture. The short fragment of Stellate gene that
      is homologous to Su(Ste) was shown to be sufficient to confer Su(Ste)-dependent
      silencing of a reporter construct in testes. We demonstrated that Su(Ste) dsRNA
      mediated silencing affects not only Stellate expression but also the level of
      sense Su(Ste) RNA providing a negative autogenous regulation of Su(Ste)
      expression. Mutation in the spindle-E gene relieving Stellate silencing also
      leads to a derepression of the other genomic tandem repeats and retrotransposons
      in the germline. CONCLUSIONS: Homology-dependent gene silencing was shown to be
      used to inhibit Stellate gene expression in the D. melanogaster germline,
      ensuring male fertility. dsRNA-mediated silencing may provide a basis for
      negative autogenous control of gene expression. The related surveillance system
      is implicated to control expression of retrotransposons in the germline.

PMID- 11470407
TI  - Thy-1 binds to integrin beta(3) on astrocytes and triggers formation of focal
      contact sites.
AB  - BACKGROUND: Thy-1 is an abundant neuronal glycoprotein in mammals. Despite such
      prevalence, Thy-1 function remains largely obscure in the absence of a defined
      ligand. Astrocytes, ubiquitous cells of the brain, express a putative Thy-1
      ligand that prevents neurite outgrowth. In this paper, a ligand molecule for Thy
      1 was identified, and the consequences of Thy-1 binding for astrocyte function
      were investigated. RESULTS: Thy-1 has been implicated in cell adhesion and,
      indeed, all known Thy-1 sequences were found to contain an integrin binding, RGD
      like sequence. Thy-1 interaction with beta3 integrin on astrocytes was
      demonstrated in an adhesion assay using a thymoma line (EL-4) expressing high
      levels of Thy-1. EL-4 cells bound to astrocytes five times more readily than EL
      4(-f), control cells lacking Thy-1. Binding was blocked by either anti-Thy-1 or
      anti-beta3 antibodies, by RGD-related peptides, or by soluble Thy-1-Fc chimeras.
      However, neither RGE/RLE peptides nor Thy-1(RLE)-Fc fusion protein inhibited the
      interaction. Immobilized Thy-1-Fc, but not Thy-1(RLE)-Fc fusion protein supported
      the attachment and spreading of astrocytes in a Mn(2+)-dependent manner. Binding
      to Thy-1-Fc was inhibited by RGD peptides. Moreover, vitronectin, fibrinogen,
      denatured collagen (dcollagen), and a kistrin-derived peptide, but not
      fibronectin, also mediated Mn(2+)-dependent adhesion, suggesting the involvement
      of beta3 integrin. The addition of Thy-1 to matrix-bound astrocytes induced
      recruitment of paxillin, vinculin, and focal adhesion kinase (FAK) to focal
      contacts and increased tyrosine phosphorylation of proteins such as p130(Cas) and
      FAK. Furthermore, astrocyte binding to immobilized Thy-1-Fc alone was sufficient
      to promote focal adhesion formation and phosphorylation on tyrosine. CONCLUSIONS:
      Thy-1 binds to beta3 integrin and triggers tyrosine phosphorylation of focal
      adhesion proteins in astrocytes, thereby promoting focal adhesion formation, cell
      attachment, and spreading.

PMID- 11470408
TI  - Expression of dominant-negative and chimeric subunits reveals an essential role
      for beta1 integrin during myelination.
AB  - Myelination represents a remarkable example of cell specialization and cell-cell
      interaction in development. During this process, axons are wrapped by concentric
      layers of cell membrane derived either from central nervous system (CNS)
      oligodendrocytes or peripheral nervous system Schwann cells. In the CNS,
      oligodendrocytes elaborate a membranous extension with an area of more than 1000
      times that of the cell body. The mechanisms regulating this change in cell shape
      remain poorly understood. Signaling mechanisms regulated by cell surface adhesion
      receptors of the integrin family represent likely candidates. Integrins link the
      extracellular environment of the cell with both intracellular signaling molecules
      and the cytoskeleton and have been shown to regulate the activity of GTPases
      implicated in the control of cell shape. Our previous work has established that
      oligodendrocytes and their precursors express a limited repertoire of integrins.
      One of these, the alpha6beta1 laminin receptor, can interact with laminin-2
      substrates to enhance oligodendrocyte myelin membrane formation in cell culture.
      However, these experiments do not address the important question of integrin
      function during myelination in vivo, nor do they define the respective roles of
      the alpha and beta subunits in the signaling pathways involved. Here, we use a
      dominant-negative approach to provide, for the first time, evidence that beta1
      integrin function is required for myelination in vivo and use chimeric integrins
      to dissect apart the roles of the extracellular and cytoplasmic domains of the
      alpha6 subunit in the signaling pathways of myelination.

PMID- 11470409
TI  - Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required
      for muscle and gonad development.
AB  - SIX5 belongs to a family of highly conserved homeodomain transcription factors
      implicated in development and disease. The mammalian SIX5/SIX4 gene pair is
      likely to be involved in the development of mesodermal structures. Moreover, a
      variety of data have implicated human SIX5 dysfunction as a contributor to
      myotonic dystrophy type 1 (DM1), a condition characterized by a number of
      pathologies including muscle defects and testicular atrophy. However, this link
      remains controversial. Here, we investigate the Drosophila gene, D-Six4, which is
      the closest homolog to SIX5 of the three Drosophila Six family members. We show
      by mutant analysis that D-Six4 is required for the normal development of muscle
      and the mesodermal component of the gonad. Moreover, adult males with defective D
      Six4 genes exhibit testicular reduction. We propose that D-Six4 directly or
      indirectly regulates genes involved in the cell recognition events required for
      myoblast fusion and the germline:soma interaction. While the exact phenotypic
      relationship between D-Six4 and SIX4/5 remains to be elucidated, the defects in D
      Six4 mutant flies suggest that human SIX5 should be more strongly considered as
      being responsible for the muscle wasting and testicular atrophy phenotypes in
      DM1.

PMID- 11470410
TI  - Ancient asymmetries in the evolution of flowers.
AB  - Dorsoventral asymmetry in flowers is thought to have evolved many times
      independently as a specialized adaptation to animal pollinators. To understand
      how such a complex trait could have arisen repeatedly, we have compared the
      expression of a gene controlling dorsoventral asymmetry in Antirrhinum with its
      counterpart in Arabidopsis, a distantly related species with radially symmetrical
      flowers. We found that the Arabidopsis gene is expressed asymmetrically in floral
      meristems, even though they are destined to form symmetrical flowers. This
      suggests that, although the flowers of the common ancestor were probably radially
      symmetrical, they may have had an incipient asymmetry, evident at the level of
      early gene activity, which could have been recruited many times during evolution
      to generate asymmetric flowers.

PMID- 11470411
TI  - The Saccharomyces recombination protein Tid1p is required for adaptation from
      G2/M arrest induced by a double-strand break.
AB  - Saccharomyces cells with a single unrepaired double-strand break (DSB) will adapt
      to checkpoint-mediated G2/M arrest and resume cell cycle progression. The
      decision to adapt is finely regulated by the extent of single-stranded DNA
      generated from a DSB. We show that cells lacking the recombination protein Tid1p
      are unable to adapt, but that this defect is distinct from any role in
      recombination. As with the adaptation-defective mutations yku70Delta and cdc5-ad,
      permanent arrest in tid1Delta is bypassed by the deletion of the checkpoint gene
      RAD9. Permanent arrest of tid1Delta cells is suppressed by the rfa1-t11 mutation
      in the ssDNA binding complex RPA, similar to yku70Delta, whereas the defect in
      cdc5-ad is not suppressed. Unlike yku70Delta, tid1Delta does not affect 5'-to-3'
      degradation of DSB ends. The tid1Delta defect cannot be complemented by
      overexpressing the homolog Rad54p, nor is it affected in rad51Delta tid1Delta,
      rad54Delta tid1Delta, or rad52Delta tid1Delta double mutants that prevent
      essentially all homologous recombination. We suggest that Tid1p participates in
      monitoring the extent of single-stranded DNA produced by resection of DNA ends in
      a fashion that is distinct from its role in recombination.

PMID- 11470412
TI  - A simple rule of thumb for elegant prehension.
AB  - Reaching out to grasp an object (prehension) is a deceptively elegant and skilled
      behavior. The movement prior to object contact can be described as having two
      components, the movement of the hand to an appropriate location for gripping the
      object, the "transport" component, and the opening and closing of the aperture
      between the fingers as they prepare to grip the target, the "grasp" component.
      The grasp component is sensitive to the size of the object, so that a larger
      grasp aperture is formed for wider objects; the maximum grasp aperture (MGA) is a
      little wider than the width of the target object and occurs later in the movement
      for larger objects. We present a simple model that can account for the temporal
      relationship between the transport and grasp components. We report the results of
      an experiment providing empirical support for our "rule of thumb." The model
      provides a simple, but plausible, account of a neural control strategy that has
      been the center of debate over the last two decades.

PMID- 11470413
TI  - Critical role for the EB1 and APC interaction in the regulation of microtubule
      polymerization.
AB  - Human EB1 was originally cloned as a protein that interacts with the COOH
      terminus of adenomatous polyposis coli (APC). Interestingly, this interaction is
      often disrupted in colon cancer, due to mutations in APC. EB1 also interacts with
      the plus-ends of microtubules and targets APC to microtubule tips. Since APC is
      detected on the kinetochores of chromosomes, it has been hypothesized that the
      EB1-APC interaction connects microtubule spindles to the kinetochores and
      regulates microtubule stability. In yeast, EB1 regulates microtubule dynamics,
      and its binding domain in APC may be conserved in Kar9, an EB1 binding protein
      involved in the microtubule-capturing mechanism. These results suggest that the
      interaction of EB1 and APC is important and may be conserved. However, it is
      largely unknown whether the EB1-APC interaction affects microtubule dynamics.
      Here, we show that EB1 potently promotes microtubule polymerization in vitro and
      in permeabilized cells, but, surprisingly, only in the presence of the COOH
      terminal EB1 binding domain of APC (C-APC). Significantly, this C-APC activity is
      abolished by phosphorylation, which also disrupts its ability to bind to EB1.
      Furthermore, yeast EB1 protein effectively substitutes for the human protein but
      also requires C-APC in promoting microtubule polymerization. Finally, C-APC is
      able to promote microtubule polymerization when stably expressed in APC mutant
      cells, demonstrating the ability of C-APC to promote microtubule assembly in
      vivo. Thus, the interaction between EB1 and APC plays an essential role in the
      regulation of microtubule polymerization, and a similar mechanism may be
      conserved in yeast.

PMID- 11470414
TI  - Identification of human Asf1 chromatin assembly factors as substrates of Tousled
      like kinases.
AB  - First described in Arabidopsis thaliana, Tousled-like kinases (Tlks) are highly
      conserved in both plants and animals. In plants, Tousled kinase is essential for
      proper flower and leaf development, but no direct functional link to any other
      plant gene product has yet been established. Likewise, the role of Tlks in
      animals is unknown. In human cells, two structurally similar Tlks, Tlk1 and Tlk2,
      were recently shown to be cell cycle-regulated kinases with maximal activities
      during S phase. Here, we report the identification of two human homologs of the
      Drosophila chromatin assembly factor Asf1 (anti-silencing function 1) as
      physiological substrates of Tlks. We show that human Asf1 proteins are
      phosphorylated by Tlks both in vivo and in vitro. Furthermore, Asf1 proteins are
      phosphorylated during S phase, when Tlks are maximally active. Conversely, Asf1
      proteins are dephosphorylated upon the activation of the DNA replication
      checkpoint, concomitant with the rapid inactivation of Tlks. These data indicate
      that Tlk family members regulate chromatin assembly during DNA replication, and
      they suggest a plausible explanation for the pleiotropic developmental defects of
      plant tousled mutants.

PMID- 11470415
TI  - A yeast homolog of the mammalian mannose 6-phosphate receptors contributes to the
      sorting of vacuolar hydrolases.
AB  - The soluble hydrolases of the mammalian lysosome are marked for delivery to this
      organelle by the addition of mannose 6-phosphate to their N-glycans. Two related
      mannose 6-phosphate receptors (MPRs) recognize this feature in the trans Golgi
      network (TGN) and deliver the hydrolases to the late endosome. In contrast, the
      vacuolar hydrolases of the yeast Saccharomyces cerevisiae do not contain 6
      phosphate monoesters on their N-glycans, and the only sorting receptor so far
      identified in this organism is the product of the VPS10 gene. This protein also
      cycles between the Golgi and the late endosome, but is unrelated to the
      vertebrate MPRs, and recognizes a specific amino acid sequence of
      carboxypeptidase Y (CPY). This has led to the notion that although yeast and
      mammals share many components in Golgi to endosome traffic, they use unrelated
      receptor systems to sort their abundant soluble hydrolases. In this paper, we
      report that the yeast genome does in fact contain an uncharacterized ORF
      (YPR079w) that encodes a membrane protein that is distantly related to mammalian
      MPRs. The protein encoded by this gene (which we term MRL1) cycles through the
      late endosome. Moreover, there is a strong synergistic effect on the maturation
      of proteinases A and B when both MRL1 and VPS10 are deleted, which suggests that
      Mrl1p may serve as a sorting receptor in the delivery of vacuolar hydrolases.

PMID- 11470416
TI  - Countering the commercial pressures.

PMID- 11470417
TI  - Putting science across.

PMID- 11470418
TI  - The MRH domain suggests a shared ancestry for the mannose 6-phosphate receptors
      and other N-glycan-recognising proteins.

PMID- 11470419
TI  - PTEN.

PMID- 11470420
TI  - Introducing embryonic stem cells.

PMID- 11470421
TI  - Planar polarity: getting ready to ROCK.
AB  - Cells in the Drosophila wing are polarised to produce a single distally pointing
      trichome. Recent studies show that this requires the recruitment of the
      Dishevelled protein to the distal cell edge, and the correct levels of Rho
      associated kinase activity.

PMID- 11470422
TI  - Eukaryotic transcription: the core of eukaryotic gene activation.
AB  - Gene expression is controlled by interactions between activators and
      coactivators. These interactions in turn are regulated by signaling pathways and
      by chromatin remodeling events. Recent studies indicate that the final arbiter of
      gene regulation is a coactivator scaffold at the promoter.

PMID- 11470423
TI  - Animal cytokinesis: breaking up is hard to do.
AB  - Recent studies have shed new light on how the physical association between sister
      cells is severed at the end of cytokinesis while the membrane is resealed.
      Comparisons with yeast suggest that daughter cell shape may feed back to regulate
      cytokinesis through the Bub2 checkpoint system.

PMID- 11470424
TI  - Circadian rhythms: a fine c(l)ocktail!
AB  - The central pacemaker of circadian behavior in mammals is located in the
      suprachiasmatic nuclei, each neuron of which has its own circadian rhythm. Recent
      studies shed light on the integration of these individual cellular rhythms and on
      novel genetic determinants that have been found to influence circadian behavior.

PMID- 11470425
TI  - Calcium signalling: store-operated channel found at last.
AB  - The intestinal Ca(2+) transport protein CaT1 has recently been shown to have the
      biophysical characteristics of the Ca(2+)-release activated Ca(2+) channel that
      refills internal Ca(2+) stores following agonist-elicited release. This finding
      highlights a hitherto unrecognized link between epithelial Ca(2+) transport and
      Ca(2+) signalling.

PMID- 11470426
TI  - Wnt signaling: the naked truth?
AB  - Frizzled receptors can activate two alternative signal transduction pathways: the
      canonical Wnt pathway or the planar cell polarity pathway. Recent studies of the
      Naked cuticle protein suggest a mechanism for the inactivation of the canonical
      pathway and concomitant activation of the planar cell polarity pathway.

PMID- 11470427
TI  - Genomic imprinting: mother maintains methylation marks.
AB  - A DNA methyltransferase has been identified that plays a role in maintaining the
      methylation status of imprinted genes. Interestingly, although expressed in the
      unfertilised egg, this enzyme functions only during one round of replication in
      the eight-cell embryo.

PMID- 11470428
TI  - Cytokines: IL-20 - a new effector in skin inflammation.
AB  - The newly discovered cytokine interleukin-20 (IL-20) is structurally related to
      IL-10, yet it appears to be an autocrine factor for keratinocytes that regulates
      their participation in inflammation.

PMID- 11470429
TI  - Intracellular signalling: sphingosine-1-phosphate branches out.
AB  - Recent studies indicate that sphingosine-1-phosphate - known to be an important
      signalling molecule in animal cells - is involved in Ca(2+)-dependent signalling
      in yeast and higher plants, raising the likelihood that it is a universal
      signalling molecule with a diverse range of functions in eukaryotes.

PMID- 11470430
TI  - Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide
      aglycone in the biosynthesis of vancomycin group antibiotics.
AB  - BACKGROUND: Members of the vancomycin group of glycopeptide antibiotics have an
      oxidatively crosslinked heptapeptide scaffold decorated at the hydroxyl groups of
      4-OH-Phegly4 or beta-OH-Tyr6 with mono- (residue 6) or disaccharides (residue 4).
      The disaccharide in vancomycin itself is L-vancosamine-1,2-glucose, and in
      chloroeremomycin it is L-4-epi-vancosamine-1,2-glucose. The sugars and their
      substituents play an important role in efficacy, particularly against vancomycin
      resistant pathogenic enterococci. RESULTS: The glucosyltransferase, GtfB, that
      transfers the glucose residue from UDP-glucose to the 4-OH-Phegly4 residue of the
      vancomycin aglycone, initiating the glycosylation pathway in chloroeremomycin
      maturation, has been crystallized, and its structure has been determined by X-ray
      analysis at 1.8 A resolution. The enzyme has a two-domain structure, with a deep
      interdomain cleft identified as the likely site of UDP-glucose binding. A
      hydrophobic patch on the surface of the N-terminal domain is proposed to be the
      binding site of the aglycone substrate. Mutagenesis has revealed Asp332 as the
      best candidate for the general base in the glucosyltransfer reaction.
      CONCLUSIONS: The structure of GtfB places it in a growing group of
      glycosyltransferases, including Escherichia coli MurG and a beta
      glucosyltransferase from T4 phage, which together form a subclass of the
      glycosyltransferase superfamily and give insights into the recognition of the NDP
      sugar and aglycone cosubstrates. A single major interdomain linker between the N-
      and C- terminal domains suggests that reprogramming of sugar transfer or aglycone
      recognition in the antibiotic glycosyltransferases, including the glycopeptide
      and also the macrolide antibiotics, will be facilitated by this structural
      information.

PMID- 11470431
TI  - Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g
      protein-coupled signaling to Rho GTPases.
AB  - BACKGROUND: The multidomain PDZ-RhoGEF is one of many known guanine nucleotide
      exchange factors that upregulate Rho GTPases. PDZ-RhoGEF and related family
      members play a critical role in a molecular signaling pathway from heterotrimeric
      G protein-coupled receptors to Rho proteins. A approximately 200 residue RGS-like
      (RGSL) domain in PDZ-RhoGEF and its homologs is responsible for the direct
      association with Galpha12/13 proteins. To better understand structure-function
      relationships, we initiated crystallographic studies of the RGSL domain from
      human PDZ-RhoGEF. RESULTS: A recombinant construct of the RGSL domain was
      expressed in Escherichia coli and purified, but it did not crystallize.
      Alternative constructs were designed based on a novel strategy of targeting
      lysine and glutamic acid residues for mutagenesis to alanine. A triple-point
      mutant functionally identical to the wild-type protein was crystallized, and its
      structure was determined by the MAD method using Se-methionine (Se-Met)
      incorporation. A molecular model of the RGSL domain was refined at 2.2 A
      resolution, revealing an all-helical tertiary fold with the mutations located at
      intermolecular lattice contacts. CONCLUSIONS: The first nine helices adopt a fold
      similar to that observed for RGS proteins, although the sequence identity with
      other such known structures is below 20%. The last three helices are an integral
      extension of the RGS fold, packing tightly against helices 3 and 4 with multiple
      hydrophobic interactions. Comparison with RGS proteins suggests features that are
      likely relevant for interaction with G proteins. Finally, we conclude that the
      strategy used to produce crystals was beneficial and might be applicable to other
      proteins resistant to crystallization.

PMID- 11470432
TI  - Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit
      effect at the ATPase active site of an ABC transporter.
AB  - BACKGROUND: ATP binding cassette (ABC) transporters are ubiquitously distributed
      transmembrane solute pumps that play a causative role in numerous diseases.
      Previous structures have defined the fold of the ABC and established the
      flexibility of its alpha-helical subdomain. But the nature of the mechanical
      changes that occur at each step of the chemical ATPase cycle have not been
      defined. RESULTS: Crystal structures were determined of the MJ1267 ABC from
      Methanococcus jannaschii in Mg-ADP-bound and nucleotide-free forms. Comparison of
      these structures reveals an induced-fit effect at the active site likely to be a
      consequence of nucleotide binding. In the Mg-ADP-bound structure, the loop
      following the Walker B moves toward the Walker A (P-loop) coupled to backbone
      conformational changes in the intervening "H-loop", which contains an invariant
      histidine. These changes affect the region believed to mediate intercassette
      interaction in the ABC transporter complex. Comparison of the Mg-ADP-bound
      structure of MJ1267 to the ATP-bound structure of HisP suggests that an outward
      rotation of the alpha-helical subdomain is coupled to the loss of a molecular
      contact between the gamma-phosphate of ATP and an invariant glutamine in a
      segment connecting this subdomain to the core of the cassette. CONCLUSIONS: The
      induced-fit effect and rotation of the alpha-helical subdomain may play a role in
      controlling the nucleotide-dependent change in cassette-cassette interaction
      affinity believed to represent the power-stroke of ABC transporters. Outward
      rotation of the alpha-helical subdomain also likely facilitates Mg-ADP release
      after hydrolysis. The MJ1267 structures therefore define features of the
      nucleotide-dependent conformational changes that drive transmembrane transport in
      ABC transporters.

PMID- 11470433
TI  - Crystal structure of precorrin-8x methyl mutase.
AB  - BACKGROUND: The crystal structure of precorrin-8x methyl mutase (CobH), an enzyme
      of the aerobic pathway to vitamin B12, provides evidence that the mechanism for
      methyl migration can plausibly be regarded as an allowed [1,5]-sigmatropic shift
      of a methyl group from C-11 to C-12 at the C ring of precorrin-8x to afford
      hydrogenobyrinic acid. RESULTS: The dimeric structure of CobH creates a set of
      shared active sites that readily discriminate between different tautomers of
      precorrin-8x and select a discrete tautomer for sigmatropic rearrangement. The
      active site contains a strictly conserved histidine residue close to the site of
      methyl migration in ring C of the substrate. CONCLUSION: Analysis of the
      structure with bound product suggests that the [1,5]-sigmatropic shift proceeds
      by protonation of the ring C nitrogen, leading to subsequent methyl migration.

PMID- 11470434
TI  - Crystal structure of the alpha-actinin rod reveals an extensive torsional twist.
AB  - BACKGROUND: Alpha-actinin is a ubiquitously expressed protein found in numerous
      actin structures. It consists of an N-terminal actin binding domain, a central
      rod domain, and a C-terminal domain and functions as a homodimer to cross-link
      actin filaments. The rod domain determines the distance between cross-linked
      actin filaments and also serves as an interaction site for several cytoskeletal
      and signaling proteins. RESULTS: We report here the crystal structure of the
      alpha-actinin rod. The structure is a twisted antiparallel dimer that contains a
      conserved acidic surface. CONCLUSIONS: The novel features revealed by the
      structure allow prediction of the orientation of parallel and antiparallel cross
      linked actin filaments in relation to alpha-actinin. The conserved acidic surface
      is a possible interaction site for several cytoplasmic tails of transmembrane
      proteins involved in the recruitment of alpha-actinin to the plasma membrane.

PMID- 11470435
TI  - Structure of the Bacillus cell fate determinant SpoIIAA in phosphorylated and
      unphosphorylated forms.
AB  - BACKGROUND: The asymmetric cell division during sporulation in Bacillus subtilis
      gives rise to two compartments: the mother cell and the forespore. Each follow
      different programs of gene expression coordinated by a succession of alternate
      RNA polymerase sigma factors. The activity of the first of these sigma factors,
      sigmaF, is restricted to the forespore although sigmaF is present in the
      predivisional cell and partitions into both compartments following the asymmetric
      septation. For sigmaF to become active, it must escape from a complex with its
      cognate anti-sigma factor, SpoIIAB. This relief from SpoIIAB inhibition requires
      the dephosphorylation of the anti-sigma factor antagonist, SpoIIAA. The
      phosphorylation state of SpoIIAA is thus a key determinant of sigmaF activity and
      cell fate. RESULTS: We have solved the crystal structures of SpoIIAA from
      Bacillus sphaericus in its phosphorylated and unphosphorylated forms. The overall
      structure consists of a central beta-pleated sheet, one face of which is buried
      by a pair of alpha helices, while the other is largely exposed to solvent. The
      site of phosphorylation, Ser57, is located at the N terminus of helix alpha2. The
      phosphoserine is exceptionally well defined in the 1.2 A electron density maps,
      revealing that the structural changes accompanying phosphorylation are slight.
      CONCLUSIONS: Comparison of unphosphorylated and phosphorylated SpoIIAA shows that
      covalent modification has no significant effect on the global structure of the
      protein. The phosphoryl group has a passive role as a negatively charged flag
      rather than the active role it plays as a nucleus of structural reorganization in
      many eukaryotic signaling systems.

PMID- 11470436
TI  - Crystal structures of mitochondrial processing peptidase reveal the mode for
      specific cleavage of import signal sequences.
AB  - BACKGROUND: Mitochondrial processing peptidase (MPP) is a metalloendopeptidase
      that cleaves the N-terminal signal sequences of nuclear-encoded proteins targeted
      for transport from the cytosol to the mitochondria. Mitochondrial signal
      sequences vary in length and sequence, but each is cleaved at a single specific
      site by MPP. The cleavage sites typically contain an arginine at position -2 (in
      the N-terminal portion) from the scissile peptide bond in addition to other
      distal basic residues, and an aromatic residue at position +1. Mitochondrial
      import machinery recognizes amphiphilic helical conformations in signal
      sequences. However, it is unclear how MPP specifically recognizes diverse
      presequence substrates. RESULTS: The crystal structures of recombinant yeast MPP
      and a cleavage-deficient mutant of MPP complexed with synthetic signal peptides
      have been determined. MPP is a heterodimer; its alpha and beta subunits are
      homologous to the core II and core I proteins, respectively, of the ubiquinol
      cytochrome c oxidoreductase complex. Crystal structures of two different
      synthetic substrate peptides cocrystallized with the mutant MPP each show the
      peptide bound in an extended conformation at the active site. Recognition sites
      for the arginine at position -2 and the +1 aromatic residue are observed.
      CONCLUSIONS: MPP bound two mitochondrial import presequence peptides in extended
      conformations in a large polar cavity. The presequence conformations differ from
      the amphiphilic helical conformation recognized by mitochondrial import
      components. Our findings suggest that the presequences adopt context-dependent
      conformations through mitochondrial import and processing, helical for
      recognition by mitochondrial import machinery and extended for cleavage by the
      main processing component.

PMID- 11470437
TI  - The factor VII zymogen structure reveals reregistration of beta strands during
      activation.
AB  - BACKGROUND: Coagulation factor VIIa (FVIIa) contains a Trypsin-like serine
      protease domain and initiates the cascade of proteolytic events leading to
      Thrombin activation and blood clot formation. Vascular injury allows formation of
      the complex between circulating FVIIa and its cell surface bound obligate
      cofactor, Tissue Factor (TF). Circulating FVIIa is nominally activated but
      retains zymogen-like character and requires TF in order to complete the zymogen
      to-enzyme transition. The manner in which TF exerts this effect is unclear. The
      structure of TF/FVIIa is known. Knowledge of the zymogen structure is helpful for
      understanding the activation transition in this system. RESULTS: The 2 A
      resolution crystal structure of a zymogen form of FVII comprising the EGF2 and
      protease domains is revealed in a complex with the exosite binding inhibitory
      peptide A-183 and a vacant active site. The activation domain, which includes the
      N terminus, differs in ways beyond those that are expected for zymogens in the
      Trypsin family. There are large differences in the TF binding region. An
      unprecedented 3 residue shift in registration between beta strands B2 and A2 in
      the C-terminal beta barrel and hydrogen bonds involving Glu154 provide new
      insight into conformational changes accompanying zymogen activation, TF binding,
      and enzymatic competence. CONCLUSIONS: TF-mediated allosteric control of the
      activity of FVIIa can be rationalized. The reregistering beta strand connects the
      TF binding region and the N-terminal region. The zymogen registration allows H
      bonds that prevent the N terminus from attaining a key salt bridge with the
      active site. TF binding may influence an equilibrium by selecting the
      enzymatically competent registration.

PMID- 11470438
TI  - Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a
      novel enzymatic function on an ancient metal binding scaffold.
AB  - BACKGROUND: Methylmalonyl-CoA epimerase (MMCE) is an essential enzyme in the
      breakdown of odd-numbered fatty acids and of the amino acids valine, isoleucine,
      and methionine. Present in many bacteria and in animals, it catalyzes the
      conversion of (2R)-methylmalonyl-CoA to (2S)-methylmalonyl-CoA, the substrate for
      the B12-dependent enzyme, methylmalonyl-CoA mutase. Defects in this pathway can
      result in severe acidosis and cause damage to the central nervous system in
      humans. RESULTS: The crystal structure of MMCE from Propionibacterium shermanii
      has been determined at 2.0 A resolution. The MMCE monomer is folded into two
      tandem betaalphabetabetabeta modules that pack edge-to-edge to generate an 8
      stranded beta sheet. Two monomers then pack back-to-back to create a tightly
      associated dimer. In each monomer, the beta sheet curves around to create a deep
      cleft, in the floor of which His12, Gln65, His91, and Glu141 provide a binding
      site for a divalent metal ion, as shown by the binding of Co2+. Modeling 2
      methylmalonate into the active site identifies two glutamate residues as the
      likely essential bases for the epimerization reaction. CONCLUSIONS: The
      betaalphabetabetabeta modules of MMCE correspond with those found in several
      other proteins, including bleomycin resistance protein, glyoxalase I, and a
      family of extradiol dioxygenases. Differences in connectivity are consistent with
      the evolution of these very different proteins from a common precursor by
      mechanisms of gene duplication and domain swapping. The metal binding residues
      also align precisely, and striking structural similarities between MMCE and
      glyoxalase I suggest common mechanisms in their respective epimerization and
      isomerization reactions.

PMID- 11470439
TI  - Regulation and functions of myogenic regulatory factors in lower vertebrates.
AB  - The transcription factors of the MyoD family have essential functions in myogenic
      lineage determination and muscle differentiation. These myogenic regulatory
      factors (MRFs) activate muscle-specific transcription through binding to a DNA
      consensus sequence known as the E-box present in the promoter of numerous muscle
      genes. Four members, MyoD, myogenin, myf5 and MRF4/herculin/myf6, have been
      identified in higher vertebrates and have been shown to exhibit distinct but
      overlapping functions. Homologues of these four MRFs have also been isolated in a
      variety of lower vertebrates, including amphibians and fish. Differences have
      been observed, however, in both the expression patterns of MRFs during muscle
      development and the function of individual MRFs between lower and higher
      vertebrates. These differences reflect the variety of body muscle formation
      patterns among vertebrates. Furthermore, as a result of an additional polyploidy
      that occurred during the evolution of some amphibians and fish, MyoD, myogenin,
      myf5 and MRF4 may exist in lower vertebrates in two distinct copies that have
      evolved separately, acquiring specific roles and resulting in increased
      complexity of the myogenic regulatory network. Evidence is now accumulating that
      many of the co-factors (E12, Id, MEF2 and CRP proteins) that regulate MRF
      activity in mammals are also present in lower vertebrates. The inductive signals
      controlling the initial expression of MRFs within the developing somite of lower
      vertebrate proteins are currently being elucidated.

PMID- 11470440
TI  - Molecular cloning and sequence of gilthead sea bream (Sparus aurata) alpha
      skeletal actin: tissue and developmental expression.
AB  - In the present study, the Sparus aurata alpha-skeletal actin was cloned from a
      mixed larvae complementary DNA library. The clone isolated was 1523 bp long with
      an open reading frame of 1134 bp coding for a 377-amino acid protein. The deduced
      amino acid sequence of sea bream alpha-actin is identical to Fugu alpha-actin-1.
      The expression of alpha-actin was initiated at the onset of segmentation. In
      adult fish, alpha-actin is expressed predominantly in white and red muscle.

PMID- 11470441
TI  - The potential mechanism for glutamine-induced collagen biosynthesis in cultured
      human skin fibroblasts.
AB  - Although glutamine (Gln) is known as an important stimulator of collagen
      biosynthesis in collagen-producing cells, the mechanism and endpoints by which it
      regulate the process remain largely unknown. Intermediates of Gln
      interconversion: glutamate (Glu) and pyrroline-5-carboxylate (P5C) stimulate
      collagen biosynthesis in cultured cells but evoke different maxima of collagen
      biosynthesis stimulating activity at different times of incubation. P5C was found
      to be the most potent stimulator of collagen biosynthesis after 6 h of incubation
      (approx. three-fold increase); after 12 h, it induced increase in collagen
      biosynthesis to 260%, while at 24 h, the process was decreased to approximately
      80% of control values. Glu induced increase in collagen biosynthesis to
      approximately 180%, 400% and 120% of control values, after 6, 12 and 24 h,
      respectively, suggesting that after 12 h of incubation, Glu was the most potent
      stimulator of collagen biosynthesis. Glu was also the most potent stimulator of
      type I procollagen expression at this time. After 6, 12 and 24 h incubation, Gln
      induced collagen biosynthesis to approximately 112, 115 and 230% of control
      values, respectively. Since prolidase is known to be involved in collagen
      metabolism, the enzyme activity assay was performed in fibroblasts cultured in
      the presence of Gln, Glu and P5C. While Gln and Glu required 24 h for maximal
      stimulation of prolidase activity, P5C induced it after 6-12 h. The data suggest
      that P5C induced collagen biosynthesis and prolidase activity in a shorter time
      than Gln and Glu. We considered that P5C directly stimulates the processes, while
      Gln acts through its intermediate-P5C. Reduction of P5C to proline is coupled to
      the conversion of glucose-6-phosphate (G6P) to 6-phospho-gluconate, catalyzed by
      G6P dehydrogenase. We have found that dehydroepiandrosterone (DHEA), a potent
      inhibitor of G6P dehydrogenase, inhibited a stimulatory effect of P5C on collagen
      synthesis, expression of type I collagen and prolidase activity. Our results
      postulate a potential mechanism of glutamine-induced collagen biosynthesis
      through its intermediate - P5C. P5C-dependent activation of nucleotide
      biosynthesis, prolidase activity and P5C conversion into proline may contribute
      to the stimulation of collagen biosynthesis.

PMID- 11470442
TI  - Seasonal variation of phosphatidylcholine hydroperoxides in blood of sweet smelt
      Plecoglossus altivelis.
AB  - Sweet smelt was reared at two fishery experimental stations for 5 months from
      June to October. Every 2 weeks blood was collected from the caudal vessels and,
      subsequently, the phosphatidylcholine hydroperoxide contents and the fatty acid
      compositions in the blood were determined by high-performance liquid
      chromatography and gas chromatography, respectively. The seasonal variation of
      the contents of accumulated hydroperoxides and fatty acids in the sweet smelt
      blood were observed in both experimental stations. Sweet smelt started
      performance of cucumber-like or watermelon-like aroma in the middle of July and
      the aroma was enhanced in August. The content of phosphatidylcholine
      hydroperoxides and the amount of total fatty acid in the fish blood, in terms of
      possible precursors of volatile compounds, were also extremely high in the same
      period. According to lipid peroxidation mechanisms, the strong characteristic
      aroma of sweet smelt during July to August might be due to the high contents of
      accumulated lipid hydroperoxides and polyunsaturated fatty acids in their
      tissues.

PMID- 11470443
TI  - Expression of connexin 43 mRNA and protein in developing follicles of prepubertal
      porcine ovaries.
AB  - A major form of cell-cell communication is mediated by gap junctions,
      aggregations of intercellular channels composed of connexins (Cxs), which are
      responsible for exchange of low molecular weight (<1200 Da) cytosolic materials.
      These channels are a growing family of related proteins. This study was designed
      to determine the ontogeny of connexin 43 (Cx43) during early stages of follicular
      development in prepubertal porcine ovaries. A partial-length (412 base) cDNA
      clone was obtained from mature porcine ovaries and determined to have 98%
      identity with published porcine Cx43. Northern blot analysis demonstrated a 4.3
      kb mRNA in total RNA isolated from prepubertal and adult porcine ovaries. In-situ
      hybridization revealed that Cx43 mRNA was detectable in granulosa cells of
      primary follicles but undetectable in dormant primordial follicles. The intensity
      of the signal increased with follicular growth and was greatest in the large
      antral follicles. Immunohistochemical evaluation indicated that Cx43 protein
      expression correlated with the presence of Cx43 mRNA. These results indicate that
      substantial amounts of Cx43 are first expressed in granulosa cells following
      activation of follicular development and that this expression increases
      throughout follicular growth and maturation. These findings suggest an
      association between the enhancement of intercellular gap-junctional communication
      and onset of follicular growth.

PMID- 11470444
TI  - The chemical structure of the pigments in Ara macao plumage.
AB  - Parrots (Psittaciformes) harbor unusually bright, non-carotenoid, feather
      pigments. We successfully extracted and purified a sufficient quantity of pigment
      from the red plumage of the Scarlet Macaw (Ara macao) for a partial chemical
      analysis. The extracts were analyzed by HPLC coupled with UV-VIS and mass
      spectroscopy before and after total hydrogenation. We found at least four pigment
      components. We propose a linear polyenal structure comparable with the molecules
      tetradecahexenal, hexadecaheptenal, octadecaoctenal and eicosanonenal.

PMID- 11470445
TI  - Characterization of hepatic L-threonine dehydrogenase of chicken.
AB  - The L-threonine dehydrogenase (TDH) was purified approximately 1300-fold to a
      specific activity of approximately 18000 unit mg(-1) from chicken (Gallus
      domesticus) liver mitochondria. Purification was obtained by sequential
      chromatography on DEAE Cellulose, Phenyl Sepharose High Performance hydrophobic
      interaction, Affi-Gel Blue affinity and Matrex Gel Red A columns. The molecular
      weight of the subunit was estimated to be 36 kDa by sodium dodecyl-polyacrylamide
      gel electrophoresis. An apparent molecular mass of native protein between 62 and
      74 kDa was obtained by gel filtration chromatography, suggesting a dimeric
      structure of TDH. The isoelectric point of TDH was determined by isoelectric
      focusing to be 5.3. Partial amino-terminal sequence analyses, carried out on two
      purified preparations of TDH, revealed a high degree of homology to the reported
      sequence of porcine TDH. The Michaelis constants for L-threonine and NAD for
      partially purified chicken hepatic TDH are 5.38 and 0.19 mM, respectively.

PMID- 11470446
TI  - Genetic relationship among Japanese sentinel crabs (Decapoda: Ocypodidae: genus
      Macrophthalmus).
AB  - Seven species (eight populations) of sentinel crabs (genus Macrophthalmus) from
      the Japan coast and Uca vocans and Ocypode ceratophthalma, were examined
      electrophoretically for genetic variations in 13 enzymatic and one non-enzymatic
      protein comprising 17 loci. Most species were highly differentiated from each
      other (Nei's genetic distance, 0.29-1.63). The least genetic distance was found
      between M. japonicus and M. banzai, the genetic distinctiveness of the two taxa
      being supported by three divergent loci with no common allele. The genetic
      relationships among Macrophthalmus species differed greatly from those inferred
      from morphological features, with a UPGMA tree suggesting that the sub-genus
      Macrophthalmus is polyphyletic.

PMID- 11470447
TI  - Cloning, tissue distribution and nutritional regulation of a Delta6-desaturase
      like enzyme in rainbow trout.
AB  - This report describes the cloning, nutritional regulation and tissue distribution
      of a desaturase-like enzyme in rainbow trout (Oncorhynchus mykiss). The open
      reading frame of the trout desaturase-like cDNA encodes a 454-amino acid peptide
      that contains two membrane-spanning domains, three histidine-rich regions and a
      cytochrome b5 domain, which all align perfectly with the same domains located in
      other recently identified vertebrate Delta5- and Delta6-desaturases. Nutritional
      regulation of trout desaturase-like gene expression, as well as the tissue
      expression profile, are also similar to those observed in other vertebrate Delta5
      and Delta6-desaturases. Finally, the sequence alignments between the predicted
      protein sequence of rainbow trout desaturase-like and other Delta6- and Delta5
      desaturases revealed a high percentage identity with Delta6-desaturases (64-66%
      identity with vertebrate Delta6-desaturases). These results demonstrate for the
      first time the presence and nutritional modulation of a Delta6-desaturase-like
      cDNA in rainbow trout.

PMID- 11470448
TI  - Variation in lipid composition of Chinese mitten-handed crab, Eriocheir sinensis
      during ovarian maturation.
AB  - This experiment was conducted to investigate the variation in lipid composition
      during the ovarian maturation of the crab Eriocheir sinensis. The Chinese mitten
      handed crab broodstock was divided into six different maturation periods
      according to the size and color of ovary. Ovary, hepatopancreas, muscle, and
      hemolymph of broodstock in different maturation periods were analyzed for total
      lipid and fatty acids using gas chromatography, and lipid classes by thin-layer
      chromatography. The ovarian lipid concentration (expressed as percent wet ovarian
      weight) increased steadily from stage II (5.4%) to stage IV (19.1%), and
      decreased to the lowest levels after spawning (stage V, 6.6%). The
      hepatopancreatic lipid concentration (expressed as percent wet hepatopancreatic
      weight) increased with maturity of the ovaries, reached a maximum at stage III(2)
      (29.9%), and decreased during the subsequent period to spawning (16.7%). The
      muscular and hemolymph lipid concentration did not change markedly during the
      ovarian development. These results suggest the possible movement of
      hepatopancreatic lipids to the ovaries during the ovarian maturation. Both
      triacylglycerol and phosphatidylcholine were responsible for the increase in
      ovarian lipid concentration during sexual maturation. The fatty acids of total
      lipid, triacylglycerol, and phosphatidylcholine of the ovaries did not vary
      systematically during the ovarian maturation, but the ratio between n-3PUFA
      (polyunsaturated fatty acid) and n-6PUFA did change regularly with the ovarian
      lipid. These suggest that enough PUFA, especially n-3PUFA, should be supplied to
      the crab during ovarian maturation.

PMID- 11470449
TI  - Characterization of microsomal diacylglycerol acyltransferase activity from
      bovine adipose and muscle tissue.
AB  - The activity of the triacylglycerol bioassembly enzyme, diacylglycerol
      acyltransferase (DGAT), was characterized in microsomal fractions prepared from
      bovine subcutaneous (SC) adipose, intramuscular (IM) adipose, and muscle (pars
      costalis diaphragmatis) tissue. The activity of DGAT was generally higher from SC
      adipose tissue than from IM adipose or muscle tissue. The characteristics of DGAT
      activity from the three bovine tissues resembled the activity characteristics
      observed in previous studies from various other organisms and tissues; the pH
      optimum was near neutrality, the activity was almost completely inhibited by pre
      incubation with N-ethylmaleimide (NEM), and the enzyme accepted a broad range of
      acyl-CoAs and sn-1,2-diacylglycerols. In some aspects, the SC adipose tissue DGAT
      activity was different from the DGAT activity from the other two tissues. The SC
      adipose tissue DGAT activity was not as susceptible to inhibition by NEM as the
      enzymes from the two other tissue sources, and it exhibited increased specificity
      for substrates containing oleoyl moieties. The differences in DGAT properties
      between the three bovine tissues may account to some extent for the differences
      in the relative fatty acid composition and the positional distribution of fatty
      acids in triacylglycerol between bovine tissues. The observed differences in
      enzymatic properties also support recent biochemical and molecular genetic
      observations that imply the existence of multiple DGAT genes and/or isoforms.

PMID- 11470450
TI  - Isolation and characteristics of trypsin inhibitor from the hepatopancreas of a
      squid (Todarodes pacificus).
AB  - Trypsin inhibitor was purified from the hepatopancreas of squid (Todarodes
      pacificus). The final inhibitor preparation was nearly homogeneous by SDS-PAGE
      with an estimated molecular weight of approximately 6300. The squid trypsin
      inhibitor was acid- and heat-stable, and active against trypsins from the pyloric
      ceca of starfish (Asterias amurensis) and saury (Cololabis saira) and porcine
      pancreatic trypsin. Amino acid composition of the squid trypsin inhibitor was
      compared with other invertebrate trypsin inhibitors. The squid trypsin inhibitor
      inhibited the autolysis of walleye pollock (Theragra chalcogramma) myofibrillar
      proteins.

PMID- 11470451
TI  - The blood supply of the optic nerve head and the evaluation of it - myth and
      reality.
AB  - Evidence has gradually emerged that there is vascular insufficiency in the optic
      nerve head (ONH) in both anterior ischemic optic neuropathy (AION) and
      glaucomatous optic neuropathy (GON); thus both represent ischemic disorders of
      the ONH. Together these diseases constitute a major cause of blindness or
      seriously impaired vision in man. Consequently there has recently been great
      interest in the ONH circulation in health and disease and in how to evaluate it.
      Many studies of the subject have been published, with conflicting interpretations
      and claims. The basis of the inconsistent information seems to be confusion on
      some fundamental issues concerning the ONH circulation itself. The objective of
      this paper is to differentiate myths and misconceptions from reality about the
      ONH blood supply; to elucidate the reasons for disagreement on the blood supply
      of the ONH; and to evaluate the reliability and validity of various methods
      currently used to measure ONH blood flow.

PMID- 11470452
TI  - Blood flow in the optic nerve head and factors that may influence it.
AB  - In the recent past there has been great interest in the blood supply of the optic
      nerve head (ONH), how to evaluate ONH blood flow, and what factors influence it,
      in health and disease. This is because evidence has progressively accumulated
      that there is vascular insufficiency in the ONH in both anterior ischemic optic
      neuropathy (AION) and glaucomatous optic neuropathy (GON)-two major causes of
      blindness or of seriously impaired vision in man. For the management and
      prevention of visual loss in these two disorders, a proper understanding of the
      factors that influence the blood flow in the ONH is essential. The objective of
      this paper is, therefore, to review and discuss all these factors. The various
      factors that influence the vascular resistance, mean blood pressure and
      intraocular pressure are discussed, to create a better basic understanding of the
      ONH blood flow, which may help us toward a logical strategy for prevention and
      management of ischemic disorders of the ONH.

PMID- 11470453
TI  - The corneal wound healing response: cytokine-mediated interaction of the
      epithelium, stroma, and inflammatory cells.
AB  - The corneal wound healing cascade is complex and involves stromal-epithelial and
      stromal-epithelial-immune interactions mediated by cytokines. Interleukin-1
      appears to be a master modulator of many of the events involved in this cascade.
      Keratocyte apoptosis is the earliest stromal event noted following epithelial
      injury and remains a likely target for modulation of the overall wound healing
      response. Other processes such as epithelial mitosis and migration, stromal cell
      necrosis, keratocyte proliferation, myofibroblast generation, collagen
      deposition, and inflammatory cell infiltration contribute to the wound healing
      cascade and are also likely modulated by cytokines derived from corneal cells,
      the lacrimal gland, and possibly immune cells. Many questions remain regarding
      the origin and fate of different cell types that contribute to stromal wound
      healing. Over a period of months to years the cornea returns to a state similar
      to that found in the unwounded normal cornea.

PMID- 11470454
TI  - Characteristics of the human ocular surface epithelium.
AB  - An appreciation of the biological characteristics of the human ocular surface
      epithelium affords us a great insight into the physiology of the human ocular
      surface in health and disease. Here, we review five important aspects of the
      human ocular surface epithelium. First, we recognize the discovery of corneal
      epithelial stem cells, and note how the palisades of Vogt have been suggested as
      a clinical marker of their presence. Second, we introduce the concept of the gene
      expression profile of the ocular surface epithelium as arrived at using a new
      strategy for the systematic analysis of active genes. We also provide a summary
      of several genes abundantly or uniquely expressed in the human corneal
      epithelium, namely clusterin, keratin 3, keratin 12, aldehyde dehydrogenase 3
      (ALDH3), troponin-I fast-twitch isoform, ssig-h3, cathepsin L2 (cathepsin V),
      uroplakin Ib, and Ca(2+)-activated chloride channel. Genes related to limbal and
      conjunctival epithelia are also described. Third, we touch upon the genetic
      abnormalities thought to be involved with epithelial dysfunction in Meesmann's
      dystrophy, gelatinous drop-like corneal dystrophy, and the ssig-h3-mutated
      corneal dystrophies. Fourth, we provide an update regarding the current state of
      knowledge of the role of cytokines, growth factors and apoptosis in relation to
      ocular surface homeostasis and tissue reconstruction; the main factors being
      epidermal growth factor (EGF), keratinocyte growth factor (KGF), hepatocyte
      growth factor (HGF), transforming growth factor-ss (TGF-ss), and some
      inflammatory cytokines. Fifth, corneal epithelial barrier function and
      dysfunction as measured by fluorophotometry is remarked upon, with an explanation
      of the FL-500 fluorophotometer and its ability to detect corneal epithelial
      dysfunction at a subclinical level. The research described in this review has
      undoubtedly generated a complete understanding of corneal epithelial
      pathophysiology-an understanding that, directly or indirectly, has helped advance
      the development of new therapeutic modalities for ocular surface reconstruction.

PMID- 11470455
TI  - The visual ecology of avian photoreceptors.
AB  - The spectral sensitivities of avian retinal photoreceptors are examined with
      respect to microspectrophotometric measurements of single cells,
      spectrophotometric measurements of extracted or in vitro regenerated visual
      pigments, and molecular genetic analyses of visual pigment opsin protein
      sequences. Bird species from diverse orders are compared in relation to their
      evolution, their habitats and the multiplicity of visual tasks they must perform.
      Birds have five different types of visual pigment and seven different types of
      photoreceptor-rods, double (uneven twin) cones and four types of single cone. The
      spectral locations of the wavelengths of maximum absorbance (lambda(max)) of the
      different visual pigments, and the spectral transmittance characteristics of the
      intraocular spectral filters (cone oil droplets) that also determine
      photoreceptor spectral sensitivity, vary according to both habitat and
      phylogenetic relatedness. The primary influence on avian retinal design appears
      to be the range of wavelengths available for vision, regardless of whether that
      range is determined by the spectral distribution of the natural illumination or
      the spectral transmittance of the ocular media (cornea, aqueous humour, lens,
      vitreous humour). Nevertheless, other variations in spectral sensitivity exist
      that reflect the variability and complexity of avian visual ecology.

PMID- 11470456
TI  - Cellular models of hibernating myocardium: implications for future research.

PMID- 11470457
TI  - Cardiac sodium-calcium exchanger: a double-edged sword.

PMID- 11470458
TI  - Effects of vitamin E on the endothelium: equivocal? Alpha-tocopherol and
      endothelial dysfunction.

PMID- 11470459
TI  - Submissions and impact factor 1997-2001: focus on Sweden.

PMID- 11470460
TI  - Those who faced turbulence and launched the era of flow dynamic concepts for
      cardiac investigation.
AB  - This paper puts emphasis on pioneers who developed cardiac flow dynamics concepts
      during the second half of the 20th century at a period where pressure
      measurements were the rule. Thinking flow instead of pressure dynamics
      corresponded to in-depth conceptual changes: whereas blood pressure generally has
      a single positive sign and a similar pattern at all points of a cardiac chamber
      or a vessel, flow fluctuates around the zero line and its pattern changes within
      a given cardiac chamber or vessel level. These specific changes and fluctuations
      were the exciting tools needed to renew our pathophysiological insights, just in
      time with the take off of Doppler ultrasound making noninvasive investigation of
      fluid dynamics easily available. Each decade was marked by a specific historical
      contribution to evolving concepts. Instead of a merely phenomenological approach
      to flow dynamics, pioneers assigned a value of paradigms to basic flow patterns.
      They generated a system of heuristical hypotheses which turned out to underlay a
      modernistic understanding of flow dynamics in normal and diseased hearts. So far,
      flow investigation had definitely gained acceptance completing pressure data at
      the middle of the 1980s, widely opening a breakthrough for future
      pathophysiological insights.

PMID- 11470461
TI  - Cardiac gap junction channels: modulation of expression and channel properties.
AB  - In the heart, intercellular gap junction channels constructed from connexin
      molecules are crucial for conduction of the electric impulse. Cardiomyocytes can
      be interconnected by channels composed of three types of connexin proteins: Cx40,
      Cx43 or Cx45. In mammalian hearts, these three isoforms are regionally
      differently expressed and even between the species differences exist. Each of
      these channel-types possesses specific properties and are susceptible to
      modulation by various mechanisms. In this paper we compare the differences in
      properties of these channels as deduced from studies on transfected cells and
      isolated cardiomyocytes and discuss the factors involved in modulation of channel
      properties. Next, we evaluate the consequences of alterations in expression and
      modulation of channel properties for cardiac function. Therefore, we have
      compared reports on genetically engineered animals and discuss this information
      in relation to various pathophysiological disorders.

PMID- 11470462
TI  - Adult rabbit cardiomyocytes undergo hibernation-like dedifferentiation when co
      cultured with cardiac fibroblasts.
AB  - OBJECTIVES: Little is known about the causal factors which induce the typical
      structural changes accompanying cardiomyocyte dedifferentiation in vivo such as
      in chronic hibernating myocardium. For identifying important factors involved in
      cardiomyocyte dedifferentiation, as seen in chronic hibernation, an in vitro
      model mimicking those morphological changes, would be extremely helpful. METHODS:
      Adult rabbit cardiomyocytes were co-cultured with cardiac fibroblasts. The
      typical changes induced by this culturing paradigm were investigated using
      morphometry, electron microscopy and immunocytochemical analysis of several
      structural proteins, which were used as dedifferentiation markers, i.e., titin,
      desmin, cardiotin and alpha-smooth muscle actin. RESULTS: Close apposition of
      fibroblasts with adult rabbit cardiomyocytes induced hibernation-like
      dedifferentiation, similar to the typical changes seen in chronic hibernation in
      vivo. Both changes in ultrastructure and in the protein expression pattern of
      dedifferentiation markers as seen in chronic hibernating myocardium were seen in
      the co-cultured cardiomyocytes. CONCLUSION: Hibernation-like changes can be
      induced by co-culturing adult rabbit cardiomyocytes with fibroblasts. This
      cellular model can be a valuable tool in identifying and characterizing the
      pathways involved in the dedifferentiation phenotype in vivo, and already
      suggests that many of the structural changes accompanying dedifferentiation are
      not per se dependent on a decreased oxygen availability.

PMID- 11470463
TI  - Role of the reverse mode of the Na+/Ca2+ exchanger in reoxygenation-induced
      cardiomyocyte injury.
AB  - OBJECTIVE: We have recently shown that spontaneous Ca2+ oscillations elicit
      irreversible hypercontracture of cardiomyocytes during reoxygenation. The aim of
      this study was to investigate whether influx of exterior Ca2+ through the reverse
      mode of the Na+/Ca2+ exchanger (NCE) contributes to the development of these
      oscillations and, therefore, to reoxygenation-induced hypercontracture. METHODS:
      Isolated cardiomyocytes and hearts from rats were used as models. Cardiomyocytes
      were exposed to 60 min simulated ischemia (pH(o) 6.4) and 10 min reoxygenation
      (pH(o) 7.4). During reoxygenation cardiomyocytes were superfused with medium
      containing 1 mmol/l Ca2+ (control), with nominally Ca2+-free medium or with
      medium containing 10 micromol/l KB-R 7943 (KB), a selective inhibitor of the
      reverse mode of the NCE. RESULTS: In reoxygenated cardiomyocytes rapid Ca2+
      oscillations occurred which were reduced under Ca2+-free conditions or in
      presence of KB. Hypercontracture was also significantly reduced under Ca2+-free
      conditions or in presence of KB. After 30 min of normoxic perfusion isolated rat
      hearts were subjected to 60 min global ischemia and reperfusion. KB (10
      micromol/l) was present during the first 10 min of reperfusion. LVEDP, LVdevP and
      lactate dehydrogenase (LDH) release were measured. Presence of KB reduced post
      ischemic LVEDP and improved left ventricular function (LVdevP). In KB treated
      hearts the reperfusion induced release of LDH was markedly reduced from 81.1 +/-
      9.9 (control) to 49.3 +/- 8.8 U/60 min/g dry weight. CONCLUSION: Our study shows
      that inhibition of the reverse mode of the NCE, during reperfusion only, protects
      cardiomyocytes and whole hearts against reperfusion injury.

PMID- 11470464
TI  - Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for
      congenital heart disease.
AB  - OBJECTIVE: Recently, an association between the homozygous C677T mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene in infants with congenital
      neural tube defects or congenital oral clefts has been shown. However, no data
      are available so far with respect to the MTHFR 677TT genotype in children with
      underlying structural congenital heart disease (CHD). METHODS: We investigated
      the MTHFR genotype in 114 Caucasian CHD patients aged newborn to 16 years (median
      0.6 years; 53% male) and in 228 age- and sex-matched healthy controls. RESULTS:
      In childhood patients with CHD the homozygous MTHFR 677TT genotype was found in
      21 out of 114 subjects (18.4%) compared with 21 out of 228 controls (9.2%; odds
      ratio (OR) 2.2, 95%-confidence interval (CI) 1.2-4.3; P=0.027). In patients with
      pulmonary valve stenosis, hypoplastic left heart syndrome, coarctation of the
      aorta, aortic valve stenosis or subaortic stenosis the frequency of the TT
      genotype varied between 38 and 67% with corresponding ORs from 6.1 (CI, 1.4-27.5;
      P=0.034) to 20.4 (CI, 1.8-235.0; P=0.025), whereas in other structural CHD the
      frequency of this genotype was not significantly different from the controls.
      CONCLUSIONS: With the present study we can show for the first time that the
      embryonal MTHFR 677TT genotype is significantly associated with the development
      of structural congenital heart malformations during early pregnancy. It remains
      to be clarified, whether this genotype is at least a risk marker or a risk factor
      for structural congenital heart malformations.

PMID- 11470465
TI  - Adrenomedullin is a regulated modulator of neonatal cardiomyocyte hypertrophy in
      vitro.
AB  - OBJECTIVE: Adrenomedullin is a potent hypotensive, natriuretic and diuretic
      peptide that is coexpressed in the heart with its receptor, suggesting that it
      may have localized actions as a modulator of cardiac function. Although
      expression of adrenomedullin is upregulated in the pathological heart, its
      cardiac function has not been clearly elucidated and it is not known whether this
      represents a common feature of cardiac hypertrophy, nor whether this is
      restricted to cardiac myocytes. We have determined the direct effects of
      hypertrophic agents on cardiomyocyte adrenomedullin gene expression and peptide
      secretion and have examined the effects of adrenomedullin on biochemical markers
      of cardiomyocyte hypertrophy. METHODS: Regulation of adrenomedullin expression
      and its effects on the hypertrophic response were studied in cultured rat
      neonatal ventricular cardiomyocytes. RESULTS: Incubation with phenylephrine or
      endothelin for 48 h led to a hypertrophic response with an associated fivefold
      stimulation of ANP gene expression. In contrast, adrenomedullin mRNA was
      inhibited by 30-50% in response to phenylephrine or endothelin-mediated
      hypertrophy, and this was associated with a 35-45% reduction in secretion of
      immunoreactive adrenomedullin. Phorbol ester mediated activation of protein
      kinase C and increasing intracellular Ca(2+) with ionomycin led to significant
      downregulation of adrenomedullin gene expression in cardiomyocytes. Co-incubation
      with 100 nM adrenomedullin for 48 h inhibited phenylephrine-induced cardiomyocyte
      hypertrophy as determined by protein:DNA ratio. Adrenomedullin partially blocked
      phenylephrine-mediated transcriptional activation of ANP and MLC-2 reporter gene
      expression in cardiomyocytes and this effect was mimicked by 2 microM forskolin,
      suggesting that this response was mediated via the activation of adenylate
      cyclase. CONCLUSION: These data demonstrate that the cardiomyocyte adrenomedullin
      gene is repressed by phenylephrine or endothelin-mediated hypertrophy. The
      inhibitory effects of adrenomedullin on the cardiomyocyte hypertrophic response
      suggests that this peptide acts as a regulated autocrine or paracrine modulator
      of cardiomyocyte function and that downregulation of adrenomedullin expression
      may play a role in induction and maintenance of cardiomyocyte hypertrophy.

PMID- 11470466
TI  - Cardiotrophin-1 can protect cardiac myocytes from injury when added both prior to
      simulated ischaemia and at reoxygenation.
AB  - OBJECTIVE: The cytokine cardiotrophin-1 (CT-1) has previously been shown to
      protect cultured cardiocytes from cell death induced by serum removal or hypoxia
      when administered prior to the damaging stimulus. We wished to test whether a
      similar protective effect could be observed if CT-1 was added after the ischaemic
      period and to investigate the signalling pathways involved in the protective
      effect when CT-1 is given prior to or after ischaemia. METHODS: We therefore
      examined the protective effect of CT-1 in cultured rat cardiocytes exposed to
      simulated ischaemia followed by reoxygenation when CT-1 was administered either
      prior to simulated ischaemia or at reoxygenation. RESULTS: We show that CT-1 can
      exert a protective effect against the damaging effects of simulated
      ischaemia/reoxygenation both when added after the simulated ischaemia at
      reoxygenation (P<0.05 in trypan blue, TUNEL and annexin V assays) or when added
      prior to the simulated ischaemia (P<0.05). In both cases, these protective
      effects are blocked by an inhibitor of the p42/p44 MAPK pathway (P<0.05 in all
      assays). CONCLUSION: CT-1 can protect cardiac cells when added either prior to
      simulated ischaemia or at the time of reoxygenation following simulated ischaemia
      and these effects are dependent upon its ability to activate the p42/p44 MAPK
      pathway. Hence CT-1 may have therapeutic potential when added at the time of
      reperfusion following ischaemic damage.

PMID- 11470467
TI  - Protection of ischemic hearts perfused with an anion exchange inhibitor, DIDS, is
      associated with beneficial changes in substrate metabolism.
AB  - OBJECTIVE: Metabolic interventions that promote glucose use during ischemia have
      been shown to protect the myocardium and improve functional recovery on
      reperfusion. In this study we evaluated if cardioprotection can be accomplished
      by inhibiting fatty acid uptake, which would be expected to increase glycolytic
      metabolism. METHODS: Diisothiocyanostilbene sulfonic acid (DIDS), commonly used
      to inhibit Band-3 mediated anion exchanger, and has also been demonstrated to
      inhibit fatty acid transport in adipocytes, was used to inhibit fatty acid uptake
      prior to ischemia. Isolated rat hearts were perfused with buffer containing 5 mM
      glucose, 70 mU/l insulin, 0.4 mM palmitate, and 0.4 mM albumin, paced at 300
      beats/min, and subjected to 50 min of low-flow ischemia followed by 60 min of
      reperfusion. RESULTS: Ischemic injury, as assessed by creatine kinase release,
      was diminished in hearts perfused with DIDS (334+/-72 in DIDS vs. 565+/-314 IU/g
      dry wt in controls, P<0.04). Increases in LVEDP during ischemia were attenuated
      (8+/-3 mmHg in DIDS vs. 15+/-18 mmHg in controls, P<0.03) and the % recovery of
      LV function with reperfusion was enhanced in DIDS-treated hearts (78+/-10% of
      baseline in DIDS vs. 62+/-19% of baseline in controls, P<0.04). These beneficial
      effects of DIDS were associated with increased glucose metabolism and ATP content
      during ischemia and reperfusion. Furthermore, treatment with DIDS lowered the
      accumulation of long chain acyl carnitines. CONCLUSIONS: This study demonstrates
      that DIDS protects ischemic myocardium, and is associated with inhibition of
      fatty acid uptake, improved glucose metabolism, and enhanced functional recovery
      on reperfusion. The data presented here suggest a potential role for therapeutic
      agents that lower fatty acid uptake as a metabolic adjunct in the treatment of
      myocardial ischemia.

PMID- 11470468
TI  - Simvastatin reduces reperfusion injury by modulating nitric oxide synthase
      expression: an ex vivo study in isolated working rat hearts.
AB  - OBJECTIVE: We tested the hypothesis of beneficial effects of the 3-hydroxy-3
      methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitor simvastatin in a model
      of ischemia-reperfusion, and investigated potential mechanisms. METHODS: Isolated
      working rat hearts were subjected to 15 min global ischemia and 22-180 min
      reperfusion in the presence or absence of simvastatin (10-100 microM). We
      evaluated creatinephosphokinase and nitrite levels in coronary effluent, heart
      weight changes, microvascular permeability (extravasation of fluoresceine-labeled
      albumin), ultrastructural alterations, and the expression of endothelial (e) and
      inducible (i) nitric oxide synthase (NOS) (by reverse-transcribed polymerase
      chain reaction and Western blotting) in the presence or absence of the
      transcriptional inhibitor actinomycin-D. RESULTS: Simvastatin (25 microM)
      significantly reduced myocardial damage and vascular hyperpermeability,
      concomitant with a reduction in endothelial and cardiomyocyte lesions. Protection
      became less evident at 50 microM and reverted to increased damage at 100 microM.
      At 25 microM, simvastatin significantly increased eNOS mRNA and protein compared
      with untreated hearts, probably due to a post-transcriptional regulation since
      unaltered by animal pretreatment with actinomycin D. Simvastatin also
      significantly decreased iNOS mRNA and protein, as well as nitrite production
      after ischemia-reperfusion. The addition of the NOS inhibitor N(pi)-nitro-L
      arginine methylester (L-NAME, 30 microM) to 25 microM simvastatin-treated hearts
      significantly reduced cardioprotection against ischemia-reperfusion. CONCLUSIONS:
      In this model, in the absence of perfusing granulocytes, the acute administration
      of a pharmacologically relevant simvastatin concentration reduces ischemia
      reperfusion injury and prevents coronary endothelial cell and cardiomyocyte
      damage by cholesterol-independent, NO-dependent mechanisms.

PMID- 11470469
TI  - Lipid hydroperoxide modification of proteins during myocardial ischaemia.
AB  - OBJECTIVE: Lipid hydroperoxides (LOOH) are lipid peroxidation products formed
      during oxidative stress. A component of their cytotoxicity is mediated by the
      direct modification of proteins. OBJECTIVES: (i) To assess whether ischaemia and
      reperfusion in the isolated rat heart generates LOOH-protein (ii) to characterise
      the extent, time-course and subcellular localization of any protein adducts
      formed. METHODS: Using a well-characterised antibody which binds to LOOH-modified
      proteins and densitometry of Western blots, we quantified the amounts of LOOH
      protein in control aerobically perfused rat hearts and those subjected to
      ischaemia with and without reperfusion. RESULTS: Hearts (n=3/4 group), analysed
      after various periods (0, 5, 10, 20 and 30 min) of zero-flow global ischaemia,
      exhibited a time-dependent increase in the LOOH-mediated modification of a number
      of proteins. In hearts subjected to 30 min of ischaemia and then reperfused for
      various times (0, 5, 10, 20, 30 or 60 min) no changes in LOOH-protein content
      achieved during the proceeding ischaemic episode were detected. Reperfusion after
      short periods of ischaemia (5 or 10 min) also did not result in reperfusion
      induced LOOH-protein formation. Administration of mercaptopropionylglycine (1 mM)
      to hearts for 5 min before the onset of 30 min ischaemia efficiently attenuated
      the formation of LOOH-protein, maintaining the modified proteins at control
      levels. These Western immunoblot results were confirmed by additional in situ
      immunofluorescent studies which showed marked LOOH-protein immunostaining in
      ischaemic tissue around the sarcolemmal membrane. CONCLUSIONS: We conclude that
      the modification of proteins (particularly those associated with sarcolemmal
      membranes) by LOOH during ischaemia may contribute to the pathophysiology of
      ischaemic injury. In addition, these modifications may be initiators of oxidant
      induced signal transduction pathways. These findings are consistent with an
      oxidant stress occurring during ischaemia which is not exacerbated or reduced
      during the first 60 min of reperfusion.

PMID- 11470470
TI  - Apoptotic versus autophagic cell death in heart failure.
AB  - OBJECTIVE: Progressive loss of cardiomyocytes is one of the most important
      pathogenic characteristics of heart failure. Apoptosis may be an important mode
      of cell death in heart failure but it must be demonstrated by multiple criteria
      and not just TUNEL staining alone. Previously, we and others have demonstrated
      that besides apoptosis other phenomena like active gene transcription can result
      in TUNEL positivity. Moreover, other types of cell death that are caspase
      independent could be important in heart failure. This study examined the
      hypothesis whether TUNEL labeling parallels caspase activation. METHODS: Cardiac
      tissue of patients in the terminal stage of heart failure as a consequence of
      ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) were studied.
      Embryonic mice hearts were used for positive control for detection of the
      classical apoptosis. RESULTS: In mice embryonic hearts we could clearly find
      apoptotic cell death detected by TUNEL labeling and immunohistochemistry for
      activated caspase-3. In heart failure, TUNEL-positive cardiomyocytes were
      negative for active caspase-3 but showed signs of active gene transcription (SC
      35). However, autophagic cell death could be found in 0.3% of the cardiomyocytes.
      Autophagic cell death was demonstrated by granular cytoplasmic ubiquitin
      inclusions, an established marker of autophagocytosis in neurons. Interestingly,
      these autophagic cardiomyocytes were TUNEL and activated caspase-3 negative but
      were also negative for C9, a marker for necrosis. Western blot analysis confirmed
      that in cardiomyopathies no cleavage of caspase-3 and caspase-7 occurred.
      CONCLUSION: The present study demonstrates two fundamentally different situations
      of cell death in cardiac tissue. In embryonic mice, cardiomyocytes undergo
      caspase-dependent cell death. However, cardiomyocytes in heart failure show
      caspase-independent autophagic cell death rather than apoptotic cell death.

PMID- 11470471
TI  - The nitric oxide-induced reduction in cardiac energy supply is not due to
      inhibition of creatine kinase.
AB  - OBJECTIVES: While nitric oxide (NO) is a potent vasodilator already in the nM
      range, a cGMP-independent negative inotropic effect is observed at higher
      concentrations. Since inhibition of creatine kinase (CK) by NO-induced
      nitrosylation has been proposed as a possible mechanism of action, we measured
      the flux through CK in the intact heart. METHODS: In saline perfused, paced
      guinea pig hearts 31P NMR spectroscopy was employed to directly assess the
      cardiac energy status, i.e. free energy of ATP hydrolysis (DeltaG(ATP)) and flux
      through CK using magnetization transfer in absence and presence of NO. RESULTS:
      NO (50 microM) doubled coronary flow and induced a rapid drop in left ventricular
      developed pressure (39+/-10 vs. 81+/-10 mmHg) and MVO(2) (1.3+/-0.8 vs. 3.7+/-0.5
      micromol/min/g) (n=7). This effect was associated with an immediate decrease in
      phosphocreatine (PCr) (-69%) and DeltaG(ATP). During the subsequent 35 min of NO
      infusion cardiac function and MVO(2) remained depressed, while PCr partially
      recovered. NO had no effect on the unidirectional forward flux through CK (98 +/-
      21 vs. 99 +/- 20 micromol/min/g, n=7) which was 5- to 10-fold greater than the
      rate of ATP turnover. Upon cessation of NO infusion both cardiac function and PCr
      rapidly returned to baseline values. The NO-induced fall in the myocardial energy
      status was associated with an increase in mitochondrial NADH (n=7) as assessed by
      surface fluorescence. The observed change in fluorescence was similar to that
      observed with short term ischemia. CONCLUSION: The NO-mediated depression of
      myocardial function, MVO(2) and energy status is not mediated by changes in CK
      flux. Most likely a partial blockade of mitochondrial oxidative phosphorylation
      at the level of cytochrome c oxidase is responsible for this effect.

PMID- 11470472
TI  - 3,5,3'-Triiodothyronine deprivation affects phenotype and intracellular [Ca2+]i
      of human cardiomyocytes in culture.
AB  - OBJECTIVE: A decrease in plasma T3 concentration is a frequent finding in
      patients with heart failure. However, the role of this 'low T3 syndrome' on
      disease evolution has never been clarified. As phenotypic and functional
      cardiomyocyte impairments are alterations that correlate with the failing
      myocardium, we studied the long-term effects of T3 deprivation on human
      cardiomyocyte structure and calcium handling. METHODS: Atrial cardiomyocytes and
      myocardial tissue were cultured with or without 3 nM T3. Microscopical
      examination of structural features was followed by analysis of alpha-sarcomeric
      actinin and sarcoplasmic reticulum calcium ATP-ase (SERCA-2) content. Calcium
      handling was studied by [Ca2+](i) imaging. RESULTS: When stimulated with
      cyclopiazonic acid, a SERCA-2 inhibitor, T3-deprived cardiomyocytes showed
      significantly faster (P=0.03) and more transient (P=0.04) increases in
      [Ca(2+)](i) than T3-supplemented cells. Moreover, in the T3-free cultures a
      significantly lower number of cells (P=0.003) responded to caffeine, a typical
      activator of sarcoplasmic reticulum Ca(2+)-release channel. T3-deprived
      cardiomyocytes also presented altered morphology with larger dimensions than T3
      supplemented cells (P < 0.0001). Additionally, in T3-deprived samples alpha
      sarcomeric actinin and SERCA-2 protein levels were reduced to 65.6 +/- 3% (P <
      0.0001) and 74.1 +/- 4% (P=0.005), respectively, when compared with the T3
      supplemented group. CONCLUSIONS: Our data show that human cardiomyocyte calcium
      handling and phenotype are strongly influenced by T3 suggesting important
      implications of the 'low T3 syndrome' on the progression of heart failure.

PMID- 11470473
TI  - Mechanism for muscarinic inhibition of I(Ca(L)) is determined by the path for
      elevating cyclic AMP in cardiac myocytes.
AB  - OBJECTIVE: Does carbachol (CCh) require NO/cGMP for inhibition of L-type calcium
      current (I(Ca(L))) when either adenylyl cyclase activation or phosphodiesterase
      suppression is used to raise cAMP? METHODS: The effects of the NO donor SIN-1 (3
      morpholino-sydnonimine), CCh and atrial natriuretic peptide (ANP) were evaluated
      when I(Ca(L)) had been stimulated by isoproterenol (ISO) or 3-isobutyl-1
      methylxanthine (IBMX) in guinea pig isolated ventricular myocytes (35 degrees C).
      RESULTS: Carbachol, SIN-1 or ANP did not affect basal I(Ca(L)); each inhibited
      IBMX-stimulated I(Ca(L)). Dialyzed (30-100 microM) ODQ (1H-(1,2,4)oxadiazolo(4,3
      a)quinoxalin-1-one), a soluble guanylyl cyclase (sGC) inactivator, blocked
      inhibition of IBMX-stimulated I(Ca(L)) by SIN-1 (10 microM) but not by CCh (1-100
      microM) or ANP (100 nM). Dialysis with 3 microM LY83583 (6-anilino-5,8
      quinolinedione), a particulate (pGC) and sGC inactivator, opposed muscarinic-,
      ANP- and SIN-1-induced inhibition of IBMX-stimulated I(Ca(L)). Thus CCh can
      increase cGMP synthesis via pGC. Even with 100 microM [LY83583](pip), CCh
      inhibited ISO-stimulated I(Ca(L)), an effect referable to suppression of adenylyl
      cyclase activity. However, 3 microM [LY83583](pip) prevented inhibition of ISO
      stimulated I(Ca(L)) by ANP. [LY83583](pip) did not affect inhibition by 8 bromo
      cGMP (100 microM) of ISO- or IBMX-stimulated I(Ca(L)). The observations indicate
      that: (1) myocytes have ODQ-sensitive sGC activated by NO and LY8353-sensitive
      pGC activated by ANP, (2) CCh does not inhibit I(Ca(L)) via NO, (3) the mechanism
      for muscarinic inhibition depends upon the cAMP-elevating agent and (4) LY83583
      distinguishes between two pathways for muscarinic inhibition. CONCLUSION: The
      nature of the stimulant pathway that increases cAMP determines intracellular
      transduction of muscarinic inhibition. This hypothesis accords with distinct
      cyclic nucleotide compartments for the differential expression of muscarinic
      inhibition of I(Ca(L)).

PMID- 11470474
TI  - Prevention of endothelial dysfunction in heart failure by vitamin E: attenuation
      of vascular superoxide anion formation and increase in soluble guanylyl cyclase
      expression.
AB  - OBJECTIVES: Enhanced vascular superoxide anion generation contributes to
      endothelial dysfunction in heart failure. However, the effect of long-term
      treatment with the antioxidant vitamin E is unknown. METHODS AND RESULTS:
      Relaxant responses were determined in aortic rings from Wistar rats with heart
      failure 12 weeks after myocardial infarction (MI) and compared with responses in
      tissues from sham-operated animals. From the seventh post-operative day, rats
      were given either a standard chow or a chow enriched in vitamin E (approximate
      intake 100 mg/day). In rings from rats with heart failure, acetylcholine-induced
      relaxation was attenuated (maximum relaxation, R(max) 54 +/- 3%) when compared
      with rings from sham-operated animals (79 +/- 3%, n=12, P < 0.01), while
      endothelium-independent relaxation elicited by sodium-nitroprusside was
      unchanged. Aortic superoxide generation was significantly enhanced in rats with
      heart failure. Vitamin E supplementation significantly improved acetylcholine
      induced relaxation in rats with heart failure (R(max) 75 +/- 4%, P < 0.01) and
      led to a leftward shift in sodium-nitroprusside-induced relaxation curve. Aortic
      expression of the beta(1)-subunit of soluble guanylyl cyclase was significantly
      enhanced by vitamin E supplementation. In addition, the elevated vascular
      superoxide formation was normalised by vitamin E. CONCLUSIONS: These results
      demonstrate that dietary supplementation with the antioxidant vitamin E restores
      normal endothelial function, reduces vascular superoxide anion formation and
      increases the expression of the soluble guanylyl cyclase in rats with heart
      failure.

PMID- 11470475
TI  - Nitric oxide synthase inhibition increases aortic stiffness measured by pulse
      wave velocity in rats.
AB  - OBJECTIVE: The present study was to examine whether endogenous nitric oxide (NO)
      plays a role in the regulation of vascular stiffness. METHODS: Pulse wave
      velocity (PWV) was determined as the time delay between the foot of pressure
      waves recorded simultaneously at the aortic arch and abdominal aorta (just above
      the bifurcation) in anesthetized Sprague-Dawley rats. A decrease in vascular
      compliance results in an increase in PWV. RESULTS: A bolus injection of a NO
      synthase inhibitor, L-NAME (30 mg/kg), significantly increased PWV, accompanied
      by an increase in blood pressure. Since changes in blood pressure are known to
      affect PWV, phenylephrine (PE) was administered to mimic the blood pressure
      changes induced by L-NAME, thus compensating for the pressure-dependent component
      of the PWV changes. At each given level of mean arterial pressure (MAP), PWV was
      significantly higher with L-NAME than with PE treatment, suggesting that acute
      withdrawal of endogenous NO reduces aortic compliance independent of changes in
      MAP. In rats chronically treated with L-NAME (0.5 g/l in drinking water) for 3
      weeks, PWV was even higher than those acutely treated with L-NAME (at MAP=150
      mmHg). This additional increase in vascular stiffness may be due to the
      remodeling of the vascular wall as a result of chronic NOS inhibition and
      hypertension. CONCLUSION: These data demonstrate that NO modulates vascular
      compliance independent of blood pressure changes and that an intact endogenous NO
      system is required to maintain normal vascular compliance.

PMID- 11470476
TI  - Calcium buffering in coronary smooth muscle after chronic occlusion and exercise
      training.
AB  - OBJECTIVE: Exercise promotes "sarcoplasmic reticulum (SR) Ca2+ unloading" in
      porcine coronary smooth muscle, resulting in decreased agonist-induced Ca2+
      release. We studied Ca2+ handling in healthy, non-occluded right coronary artery
      cells from hearts chronically occluded at the circumflex artery. METHODS:
      Myoplasmic free Ca2+ (Ca(m)) was assessed with fura-2 in cells from sedentary
      (n=8) and aerobically exercise-trained (n=6) female Yucatan pigs after 6-month
      circumflex artery ameroid occlusion (OCC) and in cells from non-occluded,
      sedentary pigs (SED, n=5). First, Ca influx was induced by 80 mM KCl
      depolarization (priming step) followed by 5 mM caffeine to elicit maximal Ca2+
      release and depletion. The SR was Ca-loaded again by depolarization and then
      exposed to caffeine after 2- or 11-min recovery to compare SR Ca2+ unloading.
      RESULTS: Baseline Ca(m), caffeine-induced peak Ca(m), and depolarization-induced
      maximum Ca(m) were decreased, and depolarization-induced time-to-half-maximum was
      increased in OCC vs. SED pigs, suggesting a tonic Ca2+ buffering (lowering)
      effect of occlusion. Exercise did not alter these effects. SR Ca2+ unloading
      occurred only in SED, as evidenced by decreased caffeine-induced Ca2+ release
      after 11 min of recovery, and was inhibited by low extracellular Na+.
      CONCLUSIONS: SR Ca2+ unloading can be demonstrated in coronary smooth muscle from
      sedentary pigs using a novel SR Ca2+ unloading protocol, and Ca2+ unloading
      partly depends on Na+-Ca2+ exchange activity. Furthermore, SR Ca2+ unloading in
      cells from non-occluded right coronary arteries of chronically circumflex
      occluded pig hearts was not altered by exercise, perhaps due to enhanced tonic
      Ca2+ extrusion versus cells from normal, sedentary animals.

PMID- 11470477
TI  - The legacy of pharmacogenetics and potential applications.
AB  - Some 40 years of pharmacogenetic research indicates that knowledge of human
      genetic diversity is essential to a broader understanding of variation in human
      drug response, and suggests that drug therapy tailored to the genetic
      characteristics of the individual may be a realistic goal. Aided by new
      technologies, molecular studies of genetic polymorphisms of many human enzymes,
      receptors, and other proteins indicate that only a limited number of important
      protein variants account for the diversity in drug response, raising the prospect
      that these variants may be cataloged relatively soon for many human populations.
      The next great challenge of pharmacogenetics is to pin down the cellular location
      and effect of these variant proteins on the pathways and networks that govern
      individual variation in responses to drugs and other exogenous chemicals. In this
      paper, we will discuss some the current challenges to progress in
      pharmacogenetics and newer strategies that might be used to improve prospects of
      drug design and personalized therapy.

PMID- 11470478
TI  - Stationary phase deletions in Escherichia coli. I--Evidence for a new deletion
      pathway.
AB  - Deletions in the plasmid pMC874 join the promoter of the km(r) (kanamycin
      resistance) gene coding for the enzyme aminoglycoside 3'-phosphotransferase to a
      promoterless lac operon downstream giving a phenotypic change from Lac(-)-
      >Lac(+). They differ from most deletions studied in Escherichia coli, which occur
      in actively dividing cells, in several important respects, as follows. (1) They
      occur in "resting" cells incubating on McConkey's or minimal lactose agar and
      increase in number gradually over a period of 1-2 weeks. Thus, like "adaptive"
      mutations, they are time rather than generation dependent. (2) They are extremely
      rare events (frequency 1x10(-11)-5x10(-11)) in wild type cells, but their
      frequency is increased between 1 and 2 orders of magnitude by null recC(-)
      mutations. In these respects they differ from "adaptive" mutations which are
      equally frequent in recC(+) and recC(-) cells. (3) Their frequency is not
      increased by mutations which stimulate log phase deletions. (4) Based on a
      computer search for homologies and sequencing of one deletion, it appears that
      they differ from log phase deletions in that they can occur in the absence of
      major terminal homologies (direct repeats) or intervening homologies (inverted
      repeats) which could stabilize a transient secondary structure and determine the
      deletion endpoints. Thus, they are not explained by the misaligned mutagenesis
      model. In conclusion, resting phase deletions occur through a totally different
      pathway from deletions in actively dividing cells and probably originate from
      unrepaired double strand breaks.

PMID- 11470479
TI  - Stationary phase deletions in Escherichia coli. II. Mutations which stimulate
      stationary phase deletions in plasmid pMC874.
AB  - Deletions in the plasmid pMC874 take place in resting cells incubating on
      McConkey's or minimal lactose agar and are time rather than generation dependent.
      These deletions join the km(r) promoter to a promoterless lac operon giving rise
      to Lac(+) papillae on McConkey's lactose agar, and can occur in the absence of
      sequence homologies such as direct or inverted repeats. Using this as a selective
      screen we isolated 31 mutants designated dli (for deletion increase), which
      enhanced to different extents the frequency of this unusual class of deletions.
      Six of these were characterized by phenotypic tests and their ability to
      stimulate other deletion events such as the excision of Tn10 from various
      chromosomal sites and the loss of cloned fragments between two EcoR1 sites in the
      gene for chloramphenicol resistance (cat) of plasmid pBR325. Two of them showed
      contrasting phenotypes and were studied further: one (dli1) stimulated Lac(+)
      deletions in pMC874 in resting cells but not Tn10 excision from chromosomal
      locations in log phase cells, and the other one (dli2) did exactly the reverse,
      i.e. it enhanced Tn10 excision but not Lac(+) deletion incidence. Mapping and
      complementation tests showed that dli1 is a null mutation in recC and was renamed
      recC2251. This is strong evidence that resting phase deletions in pMC874 are
      stimulated by the absence of a functional RecBCD enzyme. The dli2 mutation was
      identified by mapping and phenotypic tests as a mutation in uvrD, the gene for
      helicase II, and it was tentatively designated uvrD(-)dli2. These results show
      that (1) pMC874 is an excellent system to select mutants for genetic functions
      involved in the generation of resting phase deletions, and (2) there are at least
      two major deletion pathways in E. coli, one active in resting and the other in
      actively dividing cells.

PMID- 11470480
TI  - In vivo radioprotection by alpha-TMG: preliminary studies.
AB  - alpha-TMG is a novel water-soluble derivative of Vitamin E that has shown
      excellent antioxidant activity. The parent compound has demonstrated protection
      against radiation induced chromosomal damage in vivo. Hence, the preliminary
      experiments to determine the radioprotective activity of alpha-TMG were carried
      out in adult Swiss albino mice. Acute toxicity of the drug was studied taking
      24h, 72 h and 30 day mortality after a single intraperitoneal injection of 500
      2000 mg/kg body weight of the drug. The drug LD(50) for 24h and 72 h/30 day
      survival were found to be 1120 and 1000 mg/kg body weight, respectively. The
      optimum time of drug administration and drug dose-dependent effect on in vivo
      radiation protection of bone marrow chromosomes was studied in mice. Injection of
      600 mg/kg of the drug 15 min before or within 5, 15 or 30min after 3Gy whole body
      gamma radiation resulted in a significant decrease in the aberrant metaphases
      percent at 24h post-irradiation; the maximum effect was seen when the drug was
      given immediately after irradiation. Injection of 200-800 mg/kg TMG within 5 min
      of irradiation with 3 Gy produced a significant dose-dependent reduction in the
      radiation induced percent aberrant metaphases and in the frequency of
      micronucleated erythrocytes at 24h after exposure, with a corresponding decrease
      in the different types of aberrations. The optimum dose for protection without
      drug toxicity was 600 mg/kg body weight. At this dose, TMG produced 70 and >60%
      reduction in the radiation induced percent aberrant metaphases and micronucleated
      erythrocytes, respectively. The high water solubility and effectiveness when
      administered post-irradiation favor TMG as a likely candidate for protection in
      case of accidental exposures.

PMID- 11470481
TI  - Reduction of ENU-induced transversion mutations by the isoflavone genistein in
      Escherichia coli.
AB  - In studies of mutagenesis induced by the carcinogen N-ethyl-N-nitrosourea (ENU)
      in the bacterium Escherichia coli FX-11, it was observed that G:C to A:T
      transitions did not require the inducible umuDC gene products, while a portion of
      the A:T to G:C transitions and all transversion mutations were dependent on a
      functional umuC gene. This observation suggested that the different base
      substitutions may result from differential processing of specific DNA adducts
      produced by ENU. To further understand these processes, we have investigated the
      effect of the soybean isoflavone genistein on the production of ENU-induced
      mutations. This compound, in particular, has been shown to exhibit numerous
      effects including the inhibition of the growth or proliferation of a variety of
      cancers, inhibition of angiogenesis, inhibition of tyrosine protein kinases and
      anti-oxidant properties. In our experiments, tyrosine defective (TyrA(-)) E. coli
      were exposed to ENU and a portion of the ENU-treated cells were exposed to
      genistein. The results showed a three-fold reduction in the overall mutation
      frequency when cells were treated with genistein subsequent to ENU-exposure and
      this anti-mutagenic effect was dependent on the dose of genistein employed.
      However, only certain types of base substitution mutagenesis were affected. In
      particular, transversion mutations were reduced an average of about 8.5-fold,
      while transitions were not greatly affected. In addition, UV-mutagenesis was
      reduced about three-fold and induction of the SOS response (as monitored with a
      sulA-lacZ fusion) was decreased. These results suggest that genistein may
      interfere with expression of the SOS response, including the UmuC-mediated lesion
      bypass mechanism that is necessary for UV-mutagenesis and the generation of
      transversions by ENU in E. coli.

PMID- 11470482
TI  - Effects of dietary transition metals on oxidative DNA lesions in neonatal rats.
AB  - Bulky endogenous oxidative lesions (type II I-compounds) reflect DNA damage
      associated with oxidative stress. As shown by 32P-postlabeling, their levels are
      enhanced by pro-oxidant genotoxins and also shortly after normal birth in several
      rat tissues as a function of time and the maternal diet. In order to elucidate
      which dietary components contribute to postnatal DNA damage, we have focused,
      herein, on the possible role of transition metals (iron, copper, and nickel).
      Pregnant Fischer 344 (F344) rats were fed AIN-93G purified diet containing
      different amounts of iron, copper, and nickel, or Purina-5001 natural-ingredient
      diet (which contains relatively high concentrations of these metals). Type II I
      compounds were estimated by nuclease P1-enhanced 32P-postlabeling in liver and
      lung DNA of fetuses and at 24h and day 9 post-partum. Increased postnatal
      oxidative damage was detected in liver but not lung DNA of neonates exposed to
      higher amounts of dietary transition metals. There were significant positive
      linear correlations between maternal transition metal intake and neonatal, but
      not fetal and maternal type II I-compound levels. The results show that
      transition metals in the maternal diet affect perinatal oxidative DNA damage,
      presumably via a Fenton-type reaction. They also provide evidence for optimal
      levels in the maternal diet of transition metals, which on one hand, are
      essential for life, but on the other, can cause potentially deleterious DNA
      alterations in the offspring.

PMID- 11470483
TI  - Ethanol enhances the formation of endogenously and exogenously derived adducts in
      rat hepatic DNA.
AB  - To investigate the role of ethanol in chemically-induced carcinogenesis, we
      exposed Wistar rats to ethanol, either as an acute dose or for prolonged periods
      in a liquid diet and looked for effects on endogenously and exogenously derived
      DNA adducts. Changes in the cytochrome P450 protein (CYP 2E1) and its catalytic
      demethylase activity were also followed in order to provide a sequence of
      relatively well understood changes that are associated with free radical
      production and, therefore, potentially capable of affecting DNA. The exocyclic
      DNA adducts, ethenodeoxyadenosine (varepsilondA) and ethenodeoxycytidine
      (varepsilondC), known to arise from oxidative stress and lipid peroxidation (LPO)
      sources, were detected in the liver DNA of Wistar rats at background
      concentrations of 4-6 (varepsilondA) and 25-35 (varepsilondC) adducts per 10(9)
      parent bases. When rats were given either an acute dose of ethanol (5g/kg, i.g.)
      or exposed for 1 week to ethanol in a liquid diet (5%, w/v), etheno adduct levels
      were increased approximately 2-fold and this was statistically significant for
      varepsilondC (P<0.05 and P<0.02, respectively) for the two separate treatments.In
      N-nitrosodimethylamine (NDMA)-treated rats, acute ethanol treatment significantly
      increased the level of O(6)-methylguanine (O(6)-MeG) in hepatic DNA and this was
      paralleled by a decrease in O(6)-alkylguanine DNA alkyltransferase (ATase)
      activity; immunohistochemistry confirmed this increase of O(6)-MeG in both
      hepatic and renal nuclei. When rats were given ethanol in the diet and treated
      with NDMA, O(6)-MeG levels in hepatic DNA increased at 1 week which coincided
      with the peak of CYP 2E1-dependent NDMA-demethylase activity. Single cell gel
      electrophoresis of liver cells showed that after 1 week of exposure to ethanol,
      there was a small but significant increase in the frequency of DNA strand breaks
      induced by NDMA (P<0.05); after 4 weeks the increase was 1.4-fold (P<0.01). Our
      results indicate that exposures to ethanol, which resulted in blood ethanol
      concentrations similar to those seen in chronic alcoholics and increased levels
      of expression of the CYP 2E1 protein can exacerbate the DNA damaging effects of
      endogenous and exogenous alkylating agents. These observations provide
      indications of possible mechanisms for the carcinogenic or co-carcinogenic action
      of ethanol.

PMID- 11470484
TI  - The importance of using absolute mutant frequencies to compare mutation spectra.
AB  - Because damage to the cellular DNA is very hazardous for a cell, it is important
      to identify compounds, which can cause DNA damage. To investigate the mutagenic
      effect of a particular agent of interest, usually mutation spectra are determined
      in a selected target gene. The most commonly used method to compare different
      mutation spectra with each other, is the comparison of the percentages of each
      type of mutation. In this paper, it is emphasized that comparison of percentages
      can lead to incorrect conclusions and therefore another determinant, the absolute
      mutant frequency, should be used.

PMID- 11470485
TI  - Mechanism of metal-mediated DNA damage induced by metabolites of carcinogenic 2
      nitropropane.
AB  - 2-Nitropropane (2-NP), a widely used industrial solvent, is carcinogenic to rats.
      To clarify the mechanism of carcinogenesis by 2-NP, we investigated DNA damage by
      2-NP metabolites, N-isopropylhydroxylamine (IPHA) and hydroxylamine-O-sulfonic
      acid (HAS), using 32P-5'-end-labelled DNA fragments obtained from genes that are
      relevant to human cancer. In the presence of Fe(III) EDTA, both IPHA and HAS
      caused DNA damage at every nucleotide position without marked site preference.
      The damage was inhibited by free hydroxyl radical (-*OH) scavengers, catalase and
      deferoxamine mesilate, an iron chelating agent. These results suggest that the
      DNA damage was caused by -*OH generated via H(2)O(2) by both IPHA and HAS. In
      contrast, in the presence of Cu(II), IPHA frequently caused DNA damage at
      thymine. The Cu(II)-mediated DNA damage caused by IPHA was inhibited by catalase,
      methional and bathocuproine, a Cu(I)-specific chelator, suggesting the
      involvement of H(2)O(2) and Cu(I). These results suggest that the DNA damage
      induced by IPHA in the presence of Cu(II) was caused by a reactive oxygen species
      like the Cu(I)-hydroperoxo complex. On the other hand, HAS most frequently
      induced DNA damage at 5'-TG-3', 5'-GG-3' and 5'-GGG-3' sequences. Catalase and
      methional only partly inhibited the Cu(II)-mediated DNA damage caused by HAS,
      suggesting that the reactive oxygen species and another reactive species
      participate in this process. Formation of 8-oxodG by IPHA or HAS increased in the
      presence of metal ions. This study suggests that metal-mediated DNA damage caused
      by 2-NP metabolites plays an important role in the mutagenicity and the
      carcinogenicity of 2-NP.

PMID- 11470486
TI  - The amyloid peptide induces early genotoxic damage in human preneuron NT2.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the
      extracellular deposition of amyloid beta-peptide (Abeta) in the brain. Abeta is
      involved in the pathogenesis of AD but the molecular mechanisms of its
      neurotoxicity are unknown. Here, we report that Abeta exposure on human
      preneuronal NT2 cells provoked a strong and early up-regulation of growth arrest
      and DNA damage inducible gene (Gadd45 mRNA), an indicator of DNA damage and DNA
      excision-repair processes, strongly suggesting that Abeta causes an early DNA
      strand breakage leading to a cellular DNA repair response. Comet assay clearly
      demonstrated that both full-length Abeta (1-42), and its minimal cytotoxic
      fragment Abeta (25-35), caused DNA breakage as early as 3h after the start of
      Abeta exposure. This extensive DNA damage provoked by Abeta constitutes an early
      event in the pathogenic cascade leading to neuronal death which could contribute
      to the neuropathogenesis of AD.

PMID- 11470487
TI  - Identification of a mutation causing increased expression of the tas gene in
      Escherichia coli FX-11.
AB  - Studies of N-ethyl-N-nitrosourea (ENU)-induced mutagenesis with a tyrosine
      auxotroph of Escherichia coli revealed a new type of revertant. This mutant
      strain was interesting because: (i) it was not a true revertant of the nonsense
      (ochre) defect nor a tRNA suppressor mutation; and (ii) it was induced by ENU to
      greater extent in a UmuC-defective host. Genetic mapping located the probable
      mutation to a region of the E. coli chromosome containing a newly described gene
      called tas. To investigate this mutation, the upstream region of the tas gene
      from both wild-type and mutant cells was cloned into a promoterless lacZ
      expression vector and recombined onto a lambda bacteriophage. Recombinant
      bacteriophage were inserted into the bacterial chromosome and beta-galactosidase
      (betaGal) assays were performed. These assays revealed an almost three-fold
      greater expression of betaGal from the mutant DNA than from the wild-type DNA.
      Sequence analysis of the region directly upstream of the tas gene revealed a G:C
      to A:T transition at base number 2263 (numbering based on GenBank Accession
      #AE000367), located within a potential promoter site. Further sequencing
      indicated no other mutations within the 1454bp region analyzed; however, there
      were several nucleotide differences seen in our B/r strain of E. coli, when
      compared with the published E. coli K-12 sequence. A total of 10 base differences
      were discovered; one in mutH, six within a potential open reading frame (ORF
      o237) and three in non-coding regions. Yet, none of the changes altered the
      predicted amino acid sequences. These results provide evidence of a mechanism for
      increased expression of the novel gene tas and support the neutral drift
      hypothesis for the evolution of DNA sequences.

PMID- 11470488
TI  - Analysis of TGF-beta type I receptor for mutations and polymorphisms in head and
      neck cancers.
AB  - Transforming growth factor-beta receptor (TbetaR)-dependent signals are critical
      for cell growth and differentiation and are often disrupted during tumorigenesis.
      The entire coding region of TbetaR-I and flanking intron sequences from 30 head
      and neck carcinomas were examined for alterations using "Cold" SSCP and direct
      sequencing. No somatic point mutations were found in the TbetaR-I gene. In
      contrast, 14 polymorphic sequence changes were detected in TbetaR-I in 13 (43%)
      of the samples, including eight (27%) nucleotide alterations identified as
      polymorphisms in an exon-1 (GCG)(9) microsatellite repeat, a previously reported
      tumor susceptibility allele. A nine base pair deletion was found in 23% of the
      samples including five heterozygous and two homozygous deletions as well as
      single homozygous 12bp deletion. Additionally, six heterozygous polymorphisms in
      intronic sequences were determined, including one heterozygous C/A genotype at
      the +82 nucleotide position of the intron-5 intervening sequence (IVS), and five
      heterozygous G/A genotypes within intron-7 at the +24 nucleotide position. Exon-1
      polymorphisms in the (GCG)(9) microsatellite region of the TbetaR-I gene and
      their association with head/neck cancers, suggest that development of these
      cancers may be a direct consequence of loss of responsiveness to TGF-beta
      mediated growth inhibition.

PMID- 11470489
TI  - Predicting toxicity: a mechanism of action model of chemical mutagenicity.
AB  - The increasing importance of theoretical studies for predicting toxicology has
      aroused the interest of many computational chemists. A new approach has been
      developed, based on studying at the molecular level two potential mechanisms of
      action that are related to compound mutagenicity. This approach is the first
      example that considers both the toxicant and the biological target molecules
      involved in the interaction. Using some calculated descriptors and a simulation
      of the interaction chemical, compounds can be classified. More important, the
      approach helps in understanding and explaining both the correct and the incorrect
      results, and gives a deeper understanding of the toxic mechanisms. The model has
      been applied to many compounds and the results are compared with experimental
      results reported for the corresponding Salmonella tests.

PMID- 11470490
TI  - Identification of connexin43 (alpha1) gap junction gene mutations in patients
      with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis
      (DGGE).
AB  - Gap junction channels formed by the connexin43 protein are considered to play
      crucial roles in development and function because they allow the direct cell-to
      cell exchange of molecules that mediate multiple signaling events. Previous
      results have shown that connexin43 channels are intricately gated by
      phosphorylation and that disruption of this regulation gives rise to severe heart
      malformations and defects of laterality in human, chick and frog. Here we report
      the identification of connexin43 gene mutations that represent a minor population
      of connexin43 alleles, which could be reliably detected by using denaturing
      gradient gel electrophoresis (DGGE) to visualize normal and mutant DNAs that were
      separately sequenced. In contrast, sequencing of total PCR products without DGGE
      pre-selection failed to consistently identify these mutations. Forty-six controls
      and 20 heart transplant recipients were examined in this study. In the latter
      group, 14 children had hypoplastic left heart syndrome (HLHS) in which connexin43
      gene defects were detected in eight. The remaining six transplant patients with
      HLHS and all controls showed no defects. All eight HLHS children with gene
      defects had the same four substitutions: two that were silent polymorphisms, and
      two that were missense, replacing arginine codons at positions 362 and 376 with
      codons for glutamines. All four of these substitutions are identical to the
      nucleotide sequence of the connexin43 pseudogene, suggesting the possibility of
      an illicit recombination. A breakpoint region was identified 5' to the mutation
      site in a 63bp domain that is 100% identical in the gene and pseudogene. Results
      from in vitro phosphorylation indicate that the absence of arginines 362 and 376
      completely abolishes phosphorylation in the connexin43 channel regulation domain
      suggesting a possible mechanism for the pathologies associated with HLHS.

PMID- 11470491
TI  - FISH analysis of telomeric repeat sequences and their involvement in chromosomal
      aberrations induced by radiomimetic compounds in hamster cells.
AB  - The behaviour of telomeric repeat sequences in Chinese hamster CHO and CHE cell
      lines treated with the radiomimetic drugs bleomycin (BLM) and streptonigrin (STN)
      and the effect of these drugs on telomerase activity was investigated.
      Fluorescence in situ hybridisation revealed that 18% of the scored aberrations
      induced by BLM and 14% of those induced by STN in CHO cells exhibited telomeric
      repeat signals. In CHE cells, 29% of the total aberrations induced by BLM and 45%
      of those induced by STN involved telomeric repeat sequences. Acentric fragments
      labelled along their entire length and translocations of telomeric repeat
      sequences were also found in both cell lines. These results suggest that
      telomeric repeat sequences are preferentially involved in chromosome breakage,
      fragility and recombination induced by radiomimetic agents. In addition, some of
      the damaged CHE cells exhibited one or more chromosomes with additional zones of
      hybridisation, indicating the possible amplification of (TTAGGG)(n) repeats by
      telomerase. However, the fact that none of the radiomimetic compounds tested
      produced any effect on telomerase activity suggests that this enzyme is not
      related to the assumed amplification events induced by BLM and STN in CHE cells.

PMID- 11470492
TI  - Inhibition by green tea catechins of metabolic activation of procarcinogens by
      human cytochrome P450.
AB  - Catechins, major polyphenol constituents of green tea, are potent chemopreventive
      agents against cancers caused by chemical carcinogens in rodents. The effects of
      four epicatechin derivatives, epigallocatechin gallate (EGCG), epicatechin
      gallate (ECG), epigallocatechin (EGC) and epicatechin (EC), on the metabolic
      activation of benzo[a]pyrene (B[a]P), 2-amino-1-methyl-6-phenylimidazo-[4,5
      b]pyridine (PhIP) and aflatoxin B(1) (AFB(1)) by human cytochrome P450 (CYP) were
      examined. B[a]P, PhIP and AFB(1) were activated by respective human CYP1A1,
      CYP1A2 and CYP3A4 expressed in the membrane fraction of genetically engineered
      Salmonella typhimurium (S. typhimurium) TA1538 cells harboring the human CYP and
      human NADPH-CYP reductase (OR), when the membrane fraction was added to S.
      typhimurium TA98. Galloylated catechins, ECG and EGCG inhibited the mutagenic
      activation potently, while EGC and EC showed relatively weak inhibitory effects.
      Catechins also inhibited the oxidations of typical substrates catalyzed by human
      CYPs, namely ethoxycoumarin O-deethylation by CYP1A1, ethoxyresorufin O
      deethylation by CYP1A2 and midazolam 1'-hydroxylation by CYP3A4. The IC(50)
      values of catechins for the inhibition of human CYP were roughly the same as
      those seen in the mutagenic activation. EGCG inhibited other forms of human CYP
      such as CYP2A6, CYP2C19 and CYP2E1, indicating the non-specific inhibitory
      effects of EGCG toward human CYPs. Furthermore, EGCG inhibited human NADPH
      cytochrome CYP reductase (OR) with a K(i) value of 2.5 microM. These results
      suggest that the inhibition of the enzyme activity of CYP is accounted for
      partially by the inhibition of OR.

PMID- 11470493
TI  - A note on the evaluation of fluctuation experiments.
AB  - Fluctuation analysis has emerged as a valuable tool for the measurement of
      mutation rates in single-cell populations. In this paper, we show how to make
      fuller use of the information supplied by the outcome of a fluctuation
      experiment. We shall extend Lea and Coulson's theory of the Luria-Delbruck
      distribution so that it accounts for residual mutation, reduced plating
      efficiency of mutants, and phenotypic lag, and establish a unifying method for
      the evaluation of fluctuation experiments in these cases and discuss its
      limitations. It will be proved that not all factors that might influence the
      distribution of mutant colonies in a fluctuation experiment can, in effect, be
      determined simultaneously. Nevertheless, it will be shown that the fluctuation
      analytic approach to the measurement of mutation rates may retain its value in
      comparison with (or may even be superior to) alternative methods. Finally, we
      give some numerical examples to illustrate our results.

PMID- 11470494
TI  - The histone deacetylase inhibitor trichostatin A reduces nickel-induced gene
      silencing in yeast and mammalian cells.
AB  - We have previously reported that nickel (Ni)-silenced expression of the URA3 gene
      in yeast (Saccharomyces cerevisiae) and gpt transgene in G12 Chinese hamster
      cells. In both cases, close proximity to a heterochromatic region was required
      for gene silencing. Yeast exposed to Ni exhibited reduced acetylation of the
      lysine residues in the N-terminal tail of histone H4. Ni-induced silencing of the
      gpt gene in mammalian cells involved hypermethylation of promoter region DNA.
      Yeast do not employ DNA methylation to silence gene expression. To determine if
      histone deacetylation participates in Ni-induced silencing of the URA3 and gpt
      genes, we exposed yeast and G12 hamster cells to the histone deacetylase
      inhibitor trichostatin A (TSA) prior to and concurrently with Ni. Treatment of
      yeast cells with 0.2-0.6mM NiCl(2) resulted in reduced expression of the URA3
      gene as assessed by increased resistance to 1g/l 5-fluorotic acid (5-FOA). This
      effect was lessened when yeast were pre-treated with 50 microg TSA/ml. Similarly,
      treatment of G12 cells with 5 ng/ml TSA during and after exposure to 0.3 microg
      Ni(3)S(2)/cm(2) reduced silencing of the gpt gene as gauged by resistance to 10
      microg/ml 6-thioguanine (6-TG). The ability of TSA alone and in combination with
      the DNA-demethylating agent (5-AzaC) to reactivate the gpt gene in Ni-silenced
      variants was also assessed. Although treatment with 100 ng/ml TSA for 48 h was
      partially effective in reactivating the gpt gene, treatment with 5 microM 5-AzaC
      was more efficacious. The greatest gpt gene reversion frequencies were observed
      following a sequential 5-AzaC/TSA treatment. Taken all together, our data from
      mammalian cells suggests that both DNA methylation and histone deacetylation
      participate in Ni-induced silencing of the gpt gene with DNA hypermethylation
      playing the more dominant role in maintaining the silenced state.

PMID- 11470495
TI  - Two novel mutations R653H and E230K in the Mediterranean fever gene associated
      with disease.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disorder caused by
      mutations in the Mediterranean fever gene (MEFV). We describe two novel missense
      mutations in MEFV, R653H and E230K. Both were found in compound heterozygosity
      with the mutation M694V in single Turkish patients with clinical syndromes
      characteristic for FMF. DNA sequencing and PCR-RFLP typing of the families
      confirmed the mutations and verified recessive modes of inheritance.

PMID- 11470496
TI  - The biogenesis and functions of lipid bodies in animals, plants and
      microorganisms.

PMID- 11470497
TI  - Things have(n't) changed!

PMID- 11470498
TI  - Social isolation of mature workers affects nestmate recognition in the ant
      Camponotus fellah.
AB  - This study investigates the role of social stimulation on nestmate recognition in
      mature workers of Camponotus fellah. We isolated 4-week-old workers before
      examining their behaviour in dyadic reunion tests. At the age of 4 weeks, workers
      are normally intolerant towards both allospecific and homospecific but
      allocolonial individuals. However, when they were isolated for up to 20 days,
      allocolonial aggressions decreased while allospecific aggression remained
      constant. Workers isolated for 20 days also engaged in allocolonial trophallaxis.
      These results suggest that workers need to be reinforced by social stimulation
      during their adult life to keep precise nestmate recognition capacities. We
      discuss our data under the perspective of recent neuroethological data in social
      insects to propose a mechanism for the formation of the neural template used in
      the nestmate recognition process.

PMID- 11470499
TI  - Observations of scent-marking and discriminating self from others by a domestic
      dog (Canis familiaris): tales of displaced yellow snow.
AB  - Little is known about what stimuli trigger urinating or scent-marking in domestic
      dogs, Canis familiaris, or their wild relatives. While it is often suggested that
      the urine of other animals influences urinating and scent-marking patterns in
      canids, this has not been verified experimentally. To investigate the role of
      urine in eliciting urinating and marking, in this pilot study I moved urine
      saturated snow ('yellow snow') from place-to-place during five winters to compare
      the responses of an adult male domestic dog, Jethro, to his own and others'
      urine. Jethro spent less time sniffing his own urine than that of other males or
      females, and that while his interest in his own urine waned with time it remained
      relatively constant for other individuals' urine. Jethro infrequently urinated
      over or sniffed and then immediately urinated over (scent-marked) his own urine.
      He marked over the urine of other males more frequently than he marked over
      females' urine. The method used here can be extended to other species for which
      experimental data are lacking. Though based on one dog, these novel data may
      further our knowledge of the role of scent-marking in territorial behavior and of
      sex differences in territory acquisition and maintenance.

PMID- 11470500
TI  - Variability in 5- and 8-year-olds' memory for duration: an interfering task in
      temporal bisection.
AB  - The purpose of this experiment was to investigate 5- and 8-year-olds' long-term
      memory for stimulus duration in a bisection task. Children were trained to
      discriminate between a short and a long standard duration presented as visual
      stimulus for 2 and 8 s, respectively. They had then to decide whether an
      intermediate stimulus duration was more similar to the short or to the long
      standard in two identical testing phases separated by an interfering task lasting
      for 15 min (immediate test vs. deferred test). The results showed that the 5- and
      the 8-year-olds produced orderly psychophysical functions. However, the 8-year
      olds produced psychophysical functions, which increased more abruptly with the
      increasing stimulus duration. Nevertheless, whatever the age of children tested,
      the psychophysical function curves were flatter in the deferred test than in the
      immediate test, and more particularly in the 5-year-olds. Furthermore, the 5-year
      olds produced fewer 'long' responses in the deferred than in the immediate test.
      Modeling of the data suggests that the variability of the representation of the
      standard in long-term memory was higher in the 5- than in the 8-year-olds and
      that the interfering task increased this memory variability.

PMID- 11470501
TI  - Prey catching in the archer fish: angles and probability of hitting an aerial
      target.
AB  - When trying to squirt down aerial arthropods, archer fishes (Toxotidae) have to
      cope with the displacement of the image of the target by refraction of light at
      the water surface. It has been suggested, and accepted, that Toxotes jaculatrix
      would avoid the effect of refraction by squirting vertically. In our previous
      study, however, Toxotes chatareus was observed to squirt under a wide range of
      angles, including angles much smaller than 90 degrees. The aim of the present
      study was to asses in T. chatareus (N=15), the frequency distribution of angles
      used, the relation between angle and probability to hit, the relation between
      target height and angle, and the smallest angles the fishes can use. The outcome
      was a distribution with a range of 102-58 degrees and a median of 74 degrees, no
      relation between angle and probability to hit, no relation between target height
      and angle and a smallest angle of 45 degrees. The results clearly indicate that
      T. chatareus does not evade the refraction effect by squirting only vertically
      (90 degrees ), but masters a considerable refraction effect thanks to a mechanism
      that is not investigated here. The capacity to hit prey under a wide range of
      angles is seen as an important adaptation to the natural habitat where the
      visibility of prey is restricted by vegetation. The constraints of the range of
      angles are discussed.

PMID- 11470502
TI  - Courtship behaviour in a lekking species: individual variations and settlement
      tactics in male little bustard.
AB  - We analysed the display behaviour of male little bustard Tetrax tetrax to
      identify displays that are used in the context of male-male competition and those
      that are used for attracting females. Courtship was the main activity of males
      during the breeding season. Calling activity occurred throughout the day, and
      leks were attended for more than 4 months. Male sexual displays included snort
      call, wing-flash, and jump display. Snort call was performed throughout the day
      and mainly involved male-male interactions. In contrast, the wing-flash display
      was given only at twilight, and was performed most commonly when a female was
      present, supporting an inter-sexual function for this display. The jump display
      was performed only in the presence of female at anytime of the day. Analysis of
      individual variations in display behaviour revealed that intra-individual
      variation was low compared to inter-individual variation, especially for the jump
      display. It is, therefore, possible that display rates provide information on
      male quality. Four male settlement patterns could be defined, singles, paired,
      lekking and satellite lekking, but only wing-flash display and stamped snort call
      differed among those categories. We suggest that satellite males are attempting
      to benefit from proximity to higher status males, in accordance with the hotshot
      hypothesis of lek evolution.

PMID- 11470503
TI  - Male bill colour and competition in zebra finches.
AB  - Several studies have assessed the role of bill colour in sexual selection and
      especially with respect to sexual preferences. Even though there are indications
      that bill colour is related to male quality, so far it has not been shown that
      bill colour influences male-male interaction. We used male zebra finches with
      artificially coloured bills in a competitive context to measure the effect of
      bill colour. In these tests the experimental bird could choose between two
      feeding sites, each near a stimulus bird with a different bill colour. We tested
      orange against red, no bird against orange/red and orange/red against green
      respectively. We found no difference in behaviour towards an orange compared to a
      red billed stimulus. However the birds spent relatively more time eating when
      alone compared to being close to a potential competitor. In addition, more time
      was spent eating than on other behaviours when the birds were close to the
      orange/red billed stimulus compared to the green billed stimulus. So, although no
      effect was found in the orange against red test, the results suggest that bill
      colour may play some role in male-male interaction.

PMID- 11470504
TI  - Structure and function of bromodomains in chromatin-regulating complexes.
AB  - Specific changes in chromatin structure are associated with transcriptional
      regulation. These chromatin alterations include both covalent modifications of
      the amino termini of histones as well as ATP-dependent non-covalent remodeling of
      nucleosomes. Certain protein domains, such as the bromodomains, are commonly
      associated with both of these classes of enzymes that alter chromatin. This
      review discusses recent advances in understanding the structure and function of
      bromodomains. Most significantly, a role of bromodomains has been revealed in
      binding to acetylated lysine residues in histone tails. Interactions between
      bromodomains and modified histones may be an important mechanism underlying
      chromatin structural changes and gene regulation.

PMID- 11470505
TI  - Exon-intron organization and chromosomal localization of the mouse monoglyceride
      lipase gene.
AB  - Monoglyceride lipase (MGL) functions together with hormone-sensitive lipase to
      hydrolyze intracellular triglyceride stores of adipocytes and other cells to
      fatty acids and glycerol. In addition, MGL presumably complements lipoprotein
      lipase in completing the hydrolysis of monoglycerides resulting from degradation
      of lipoprotein triglycerides. Cosmid clones containing the mouse MGL gene were
      isolated from a genomic library using the coding region of the mouse MGL cDNA as
      probe. Characterization of the clones obtained revealed that the mouse gene
      contains the coding sequence for MGL on seven exons, including a large terminal
      exon of approximately 2.6 kb containing the stop codon and the complete 3'
      untranslated region. Two different 5' leader sequences, diverging 21 bp upstream
      of the predicted translation initiation codon, were isolated from a mouse
      adipocyte cDNA library. Western blot analysis of different mouse tissues revealed
      protein size heterogeneities. The amino acid sequence derived from human MGL cDNA
      clones showed 84% identity with mouse MGL. The mouse MGL gene was mapped to
      chromosome 6 in a region with known homology to human chromosome 3q21.

PMID- 11470506
TI  - OsPAA2, a distinct alpha 1 subunit gene for the 20S proteasome in rice (Oryza
      sativa L.).
AB  - The 20S proteasome is the proteolytic complex that is involved in removing
      abnormal proteins and other diverse biological functions. The 20S proteasome is
      constituted of 28 subunits arranged in four rings of seven subunits, and exists
      as a hollow cylinder. The two outer rings and the two inner rings are composed of
      seven different alpha and beta type subunits, respectively, giving an alpha 7
      beta 7 beta 7 alpha 7 structure. We previously reported the primary structures of
      the 14 proteasomal subunit subfamilies in rice (Oryza sativa), representing the
      first set for all the subfamilies from monocot. In this study, a distinct cDNA
      sequence encoding the alpha1 subunit, OsPAA2, was identified. The amino acid
      sequence similarity between the two rice alpha1 subunits was as low as 59.6%,
      contrasting with those between paralogs of Arabidopsis proteasome subunit genes.
      The expression pattern of the OsPAA2 gene was different from that of another
      alpha1 gene, OsPAA1. These data suggest that OsPAA2 might play a distinct role
      from that of OsPAA1 in the 20S proteasome complex.

PMID- 11470507
TI  - Full-sized RanBPM cDNA encodes a protein possessing a long stretch of proline and
      glutamine within the N-terminal region, comprising a large protein complex.
AB  - Previously isolated RanBPM, a Ran-binding protein in the microtubule-organizing
      center, which had been thought to play a role in Ran-stimulated microtubule
      assembly, turned out to be a truncated protein. To clarify the function of
      RanBPM, we cloned the full-sized RanBPM cDNA that encodes a 90 kDa protein,
      compared to the previously isolated cDNA that encoded a 55 kDa protein. The newly
      cloned 5' coding region contains a great number of cytidine and guanidine
      nucleotides, like the CpG island. Thus, full-sized RanBPM cDNA encodes a long
      stretch of proline and glutamine residues in the N-terminal region. It comprises
      a protein complex of more than 670 kDa. Ran was detected in this complex when
      RanBPM and Ran were both ectopically expressed. New antibodies to RanBPM were
      prepared against three different regions of RanBPM. All of them detected a 90 kDa
      protein that is predominantly localized both in the nucleus and in the
      cytoplasmic region surrounding the centrosome, but none of them stained the
      centrosome. In this context, our previous notion that RanBPM is a centrosomal
      protein should be discarded. RanBPM is well conserved in the animal kingdom. It
      may play an important role in uncovering Ran-dependent nuclear events.

PMID- 11470508
TI  - Evidence for alternate splicing within the mRNA transcript encoding the DNA
      damage response kinase ATR.
AB  - Proper cellular response to genotoxic insult often requires the activity of one
      or more members of a family of high-molecular weight protein kinases referred to
      as phosphatidylinositol-3 kinase (PIK)-like proteins. While catalytic activity is
      an indispensable part of PIK-like protein function, little is currently known
      about factors that control their activity and/or functions. This deficiency
      stems, in large part, from our lack of knowledge concerning functionally
      significant subdomains within the large non-catalytic domain of these proteins.
      We have determined that the transcript encoding the PIK-like protein ATR
      undergoes alternate splicing within the region of the mRNA encoding its non
      catalytic domain. This conclusion is based on the sequencing of a human expressed
      sequence tag clone encoding a portion of the ATR cDNA, and is supported by the
      results of reverse transcriptase-polymerase chain reaction (RT-PCR) assays
      conducted on total and polyA+ RNA, as well as sequencing of cloned RT-PCR
      products. Cloning and sequencing of a segment of human genomic DNA indicated that
      this event arises from splicing of a single 192 bp exon within the ATR gene.
      Analysis of several human tissues indicated that alternate ATR transcripts are
      differentially expressed, suggesting that this region of the ATR protein may be
      of functional importance.

PMID- 11470509
TI  - Genomic organization, chromosomal localization and tissue specific expression of
      the murine Pxmp2 gene encoding the 22 kDa peroxisomal membrane protein (Pmp22).
AB  - Peroxisomes are subcellular organelles with important functions in lipid
      metabolism that are found in virtually all eucaryotic cells. The peroxisomal
      membrane contains a number of integral and peripheral membrane proteins involved
      in the import of peroxisomal matrix proteins and the transport of metabolites
      across the membrane. The most abundant peroxisomal membrane protein (Pmp) in rat
      peroxisomes is Pmp22, a 22 kDa protein of unknown function that is encoded by the
      Pxmp2 gene. To investigate the function of the Pxmp2 gene, we have initiated
      mouse knockout studies. The expression level of the Pxmp2 mRNA in mice was
      investigated by Northern blot analysis. Pxmp2 RNA was shown to be differentially
      expressed with highest expression levels in liver, kidney and in heart tissue.
      Comparison with other peroxisomal marker genes revealed that the expression of
      Pxmp2, Pmp70 (Pxmp1) and catalase was regulated independently. Using 5' and 3'
      RACE we have cloned the full-length cDNA of murine Pxmp2 which comprises 863
      nucleotides and have isolated a genomic clone containing the entire murine Pxmp2.
      We have analyzed the complete intron/exon structure of the Pxmp2 gene which
      contains five exons spanning about 11 kb on the genomic clone. All intron/exon
      splice junctions conform to the GT/AG rule. Sequence analysis of the Pxmp2 5'
      flanking region revealed that it was devoid of a TATA box, but characteristic
      promoter elements were identified within 250 base pairs upstream of the
      transcriptional start site. Using a mouse/hamster radiation hybrid panel, Pxmp2
      was localized on mouse chromosome 5 at 59 cM.

PMID- 11470510
TI  - Identification of a human homologue of the dendritic cell-associated C-type
      lectin-1, dectin-1.
AB  - Previously we identified the novel type II lectin receptor, dectin-1, that is
      expressed preferentially by murine antigen presenting dendritic cells (DC) and is
      involved in co-stimulation of T cells by DC. To identify the human homologue
      (DECTIN-1), we employed degenerative PCR amplification of mRNA isolated from DC
      and subsequent cDNA cloning. DECTIN-1 is a type II lectin receptor with high
      homology to type II lectin receptors expressed by natural killer (NK) cells. It
      contains an immunoreceptor tyrosine-based activation motif within the cytoplasmic
      domain. Human DECTIN-1 mRNA is expressed predominantly by peripheral blood
      leukocytes and preferentially by DC. The mRNA likely encodes a 33 kDa
      glycoprotein. In human epidermis, the protein is expressed selectively by
      Langerhans cells, which are an epidermal subset of DC. A truncated form of DECTIN
      1 RNA (termed T beta) encodes for a polypeptide lacking almost the entire neck
      domain, which is required for accessibility of the carbohydrate recognition
      domain to ligands. Genome analysis showed the deleted amino acid sequence in T
      beta to be encoded by an exon, indicating that T beta RNA is produced by
      alternative splicing. DECTIN-1 gene maps to chromosome 12, between p13.2 and
      p12.3, close to the NK gene complex (12p13.1 to p13.2) which contains genes for
      NK lectin receptors. Our results indicate that human DECTIN-1 shares many
      features with mouse dectin-1, including the generation of neck domain-lacking
      isoforms, which may down-regulate the co-stimulatory function of dectin-1.

PMID- 11470511
TI  - Microarray-based analysis of gene expression in very large gene families: the
      cytochrome P450 gene superfamily of Arabidopsis thaliana.
AB  - Cytochrome P450 (P450s) are heme-thiolate protein products of a very large gene
      superfamily, present in all kingdoms and involved in a variety of metabolic
      reactions. P450s are classified according to the degree of amino acid sequence
      identity, with P450s of the same family defined as having >40% identity, and
      P450s of the same subfamily having >55% identity. Currently, 273 P450 genes
      distributed over 45 families have been identified in Arabidopsis, and its genome
      is estimated to contain as many as 286. Genome-wide DNA microarrays make it
      possible to broadly correlate P450 gene activity with alterations in
      physiological or developmental states. A potential problem with microarray
      research is that sequence similarity between and within these families of closely
      related genes may lead to cross-hybridization. We designed experiments to
      systematically evaluate the specificity of P450 microarrays, and showed that
      conditions could be optimized to provide a very high degree of hybridization
      specificity. Under these conditions, and employing a 20% intensity value of
      maximum hybridization intensity as a cut-off, labeled P450 genes exhibited
      essentially no cross-hybridization between families and within subfamilies. We
      also compared the gene transcription levels of microarray probes derived from EST
      clones and from genomic DNA sequences for which ESTs were not available, using
      cDNA produced from RNA from various Arabidopsis tissue as the target. Many of the
      P450 genes displayed tissue-specific expression, leading to hypotheses as to the
      function of individual genes and their regulation. We also observed that several
      of the genomic sequences reported high levels of expression, highlighting the
      limitations of expression analysis based on ESTs alone.

PMID- 11470512
TI  - The human cDNA for a homologue of the plant enzyme 1-aminocyclopropane-1
      carboxylate synthase encodes a protein lacking that activity.
AB  - The sequences of genes encoding homologues of 1-aminocyclopropane-1-carboxylate
      (ACC) synthase, the first enzyme in the two-step biosynthetic pathway of the
      important plant hormone ethylene, have recently been found in Fugu rubripes and
      Homo sapiens (Peixoto et al., Gene 246 (2000) 275). ACC synthase (ACS) catalyzes
      the formation of ACC from S-adenosyl-L-methionine. ACC is oxidized to ethylene in
      the second and final step of ethylene biosynthesis. Profound physiological
      questions would be raised if it could be demonstrated that ACC is formed in
      animals, because there is no known function for ethylene in these organisms. We
      describe the cloning of the putative human ACS (PHACS) cDNA that encodes a 501
      amino acid protein that exhibits 58% sequence identity to the putative Fugu ACS
      and approximately 30% sequence identity to plant ACSs. Purified recombinant
      PHACS, expressed in Pichia pastoris, contains bound pyridoxal-5'-phosphate (PLP),
      but does not catalyze the synthesis of ACC. PHACS does, however, catalyze the
      deamination of L-vinylglycine, a known side-reaction of apple ACS. Bioinformatic
      analysis indicates that PHACS is a member of the alpha-family of PLP-dependent
      enzymes. Molecular modeling data illustrate that the conservation of residues
      between PHACS and the plant ACSs is dispersed throughout its structure and that
      two active site residues that are important for ACS activity in plants are not
      conserved in PHACS.

PMID- 11470513
TI  - Construction of a physical map of an autism susceptibility region in 7q32.3-q33.
AB  - The fast evolving progress of the human genome mapping and sequencing efforts
      facilitate the detection of genes also for complex traits. We focus on the
      detection of susceptibility loci for autism, a prototypical pervasive
      developmental disorder. Five genome screens worldwide have identified several
      putative locations of susceptibility genes thus far, with the most common region
      on chromosome 7q. In order to identify new candidate genes for infantile autism
      we constructed a physical map of bacterial artificial chromosome, P1-derived
      artificial chromosome and yeast artificial chromosome clones of a 3 Mb region
      between D7S1575 and D7S500, including a complete contig of the approximately 1.2
      Mb region around D7S2533, the marker with the most significant association
      result. We developed 16 novel sequence tag sites and mapped 23 genes/expressed
      sequence tags to the contigs. As this map contains a putative autistic disorder
      locus this integrated physical and transcript map provides a valuable resource
      for identification of candidate gene(s).

PMID- 11470514
TI  - Gene dosage affects the expression of the duplicated NHP6 genes of Saccharomyces
      cerevisiae.
AB  - Nhp6Ap and Nhp6Bp, which are 87% identical in sequence, are moderately abundant,
      chromosome-associated proteins from Saccharomyces cerevisiae. In wild type cells
      Nhp6Ap is present at three times the level of Nhp6Bp. The effects of altering
      NHP6A or NHP6B gene number on the expression of its partner has been examined
      using Northern blots and reporter genes. Deletion of NHP6A led to a three-fold
      increase in NHP6B synthesis while an extra copy of NHP6A reduced NHP6B expression
      two-fold. Changes in the NHP6B gene copy number caused more moderate changes in
      NHP6A synthesis. The regulation of one NHP6 gene by the other uses a mechanism
      that detects the level of Nhp6 protein (or RNA) rather than gene number, since
      overexpression of Nhp6B protein from a single gene led to a dramatic decrease in
      NHP6A synthesis. Deletion analysis showed that the regulatory element involved in
      gene dosage compensation maps to a 190 bp segment in the NHP6B promoter. The
      simplest model, that each Nhp6 protein can act as a transcriptional repressor at
      the other NHP6 gene, is not true since purified Nhp6A protein does not bind
      specifically to the NHP6B promoter region. Instead, Nhp6p appears to interact
      with or through another protein in regulating transcription from the NHP6 genes.

PMID- 11470515
TI  - Secretion of human proteins from yeast: stimulation by duplication of
      polyubiquitin and protein disulfide isomerase genes in Kluyveromyces lactis.
AB  - The efficiency of secreted production of mammalian proteins from yeasts remains
      unpredictably variable, depending on each protein. On the hypothesis that the
      control of protein conformation during protein translocation is the bottleneck in
      many cases, we examined the effects of an increased dosage of the genes coding
      for protein disulfide isomerase and of polyubiquitin on the secretion of two
      human proteins, serumalbumin and interleukin 1 beta. The yeast Kluyveromyces
      lactis was used as a production host. Duplication of either one of these genes
      had a strong stimulating effect on the production of the highly disulfide-bonded
      serumalbumin, but not of interleukin 1 beta.

PMID- 11470516
TI  - Novel target genes of the yeast regulator Pdr1p: a contribution of the TPO1 gene
      in resistance to quinidine and other drugs.
AB  - The yeast transcription factor Pdr1p regulates the expression of a number of
      genes, several of which encode ATP-driven transport proteins involved in multiple
      drug resistance. Among 20 genes containing binding consensus sequences for the
      transcription factor Pdr1p in their promoter, we studied more particularly the
      regulation and function of PDR16 (involved in phospholipid synthesis), TPO1
      (involved in vacuolar transport of polyamines), YAL061W (homologous to polyol
      dehydrogenases) and YLR346C (unknown function). We found that the regulation of
      these four genes depends on Pdr1p, since promoter activities studied by lacZ
      fusion analysis and mRNA levels studied by Northern blotting analysis changed
      upon deletion or hyperactivation by the pdr1-3 mutant of this transcription
      factor. The drug sensitivity of the strains deleted for these genes revealed that
      TPO1, a gene previously found to be involved in spermidine resistance and
      vacuolar polyamine transport, is a determinant of multidrug transporter since it
      also mediates growth resistance to cycloheximide and quinidine. This resistance
      pattern overlapped with that of YOR273C, a homolog of TPO1. These two homologous
      transporters are thus bona fide members of the phylogenetic subfamily DHA1
      (drug/proton antiport TC 2.A.1. 2) of the major facilitator superfamily. Both
      YOR273C and TPO1 as well as at least one other determinant involved in the yeast
      pleiotropic drug resistance network contribute to resistance to a quinoline
      containing antimalarial drug.

PMID- 11470517
TI  - Characterization of an SRY-like gene, DSox14, from Drosophila.
AB  - We have characterized the DSox14 gene, a new member of the family of
      transcription factors related to the mammalian sex determining factor, SRY. It
      contains two exons and the intron is large for Drosophila at 2.8 kb. The encoded
      protein consists of 691 amino acids (72 kDa) and includes an HMG box domain,
      which is closely related to the mouse Sox4 DNA binding domain. Expression of the
      DSox14 HMG box domain in vitro shows that it binds the sequence AACAAT with a
      K(d) of 190 nM, generating a bend angle of 48.6 degrees. At higher protein
      concentrations, a second HMG box binds at the recognition sequence, increasing
      the bend angle by 5 degrees. DSox14 is variably expressed throughout development
      as three alternative transcripts but not at all during the 1st and 2nd larval
      instars. The several mRNA transcripts are produced primarily from different
      transcriptional start sites. Analysis of the expression of DSox14 mRNAs during
      early development shows that they are maternally contributed at a low level and
      ubiquitously expressed during embryogenesis. The widespread pattern of expression
      suggests that DSox14 affects a large number of target genes.

PMID- 11470518
TI  - The unusually long small subunit ribosomal RNA gene found in amitochondriate
      amoeboflagellate Pelomyxa palustris: its rRNA predicted secondary structure and
      phylogenetic implication.
AB  - In order to ascertain a phylogenetic position of the freshwater amitochondriate
      amoeboflagellate Pelomyxa palustris its small subunit (SSU) rRNA gene was
      amplified and sequenced. It was shown to be 3502 bp long. The predicted secondary
      structure of its rRNA includes at least 16 separate expansion zones located in
      all the variable regions (V1-V9), as well as in some conservative gene regions.
      Most insertions are represented by sequences of low complexity that have
      presumably arisen by a slippage mechanism. Relatively conservative, uniformly
      positioned motifs contained in regions V4 and V7, as well as in some others, made
      it possible to perform folding. In maximum likelihood, maximum parsimony, and
      neighbor-joining trees, P. palustris tends to cluster with amitochondriate and
      secondary lost mitochondria amoebae and amoeboflagellates Entamoeba, Endolimax
      nana, and Phreatamoeba balamuthi, comprising together with them and aerobic
      lobose amoebae Vannella, Acanthamoeba, Balamuthia, and Hartmannella a
      monophyletic cluster. Another pelobiont, Mastigamoeba invertens, does not belong
      to this cluster. No specific similarity was discovered between the SSU rRNA of P.
      palustris and amitochondriate taxa of 'Archezoa': Diplomonada, Parabasalia,
      Microsporidia. Pelomyxa palustris SSU rRNA does not occupy a basal position in
      the phylogenetic trees and could be ascribed to the so-called eukaryotic 'crown'
      group if the composition of the latter were not so sensitive to the methods of
      tree building. Thus, molecular and morphological data suggest that P. palustris
      represents a secondarily modified eukaryotic lineage.

PMID- 11470519
TI  - Atypical multidrug resistance may be associated with catalytically active mutants
      of human DNA topoisomerase II alpha.
AB  - In human cells, atypical drug resistance was previously identified with reduced
      catalytic activity or nuclear localization efficiency of DNA topoisomerase II
      alpha (TOP2 alpha). We have shown two etoposide resistant hTOP2 alpha mutants,
      K798L and K798P confer resistance to etoposide. In this work, we showed these
      mutants are also resistant against doxorubicin and mAMSA in vivo in the yeast
      strain ISE2, rad52, top2-4 at the non-permissive temperature. We purified these
      mutants to characterize the drug resistant mechanism. Purified recombinant
      proteins were 8- to 12-fold more resistant to etoposide and doxorubicin than wild
      type TOP2 alpha, and 2-fold more resistant to amsacrine, as measured by
      accumulation of cleavable DNA. These data show that K798L and K798P may be
      intrinsically resistant against these drugs in vitro and that this character may
      confer atypical multidrug resistant phenotype in vivo in yeast.

PMID- 11470520
TI  - Optimization of transcriptional regulatory elements for constructing plasmid
      vectors.
AB  - In studies regarding both gene therapy and gene function, transgene expression by
      plasmid vectors benefits from the use of transcriptional regulatory elements
      which permit high-level gene expression. Therefore, with respect to transgene
      (luciferase) expression activity both in vitro (using HeLa, HepG2, and ECV304
      cells) and in vivo (mouse liver and skeletal muscle), we investigated the
      effective combination of commonly-used regulatory elements, such as the
      promoter/enhancer, intron, and polyadenylation signal (P(A)) sequence by
      constructing a series of plasmids that differed only in the particular sequence
      element being evaluated. Of the several promoter/enhancers that were tested,
      hybrid CA promoter/enhancer containing human cytomegalovirus immediate-early 1
      gene (CMV) enhancer and chicken beta-actin promoter with the beta-actin intron
      sequence, and the improved CMV promoter/enhancer containing the largest intron of
      CMV (intron A) produced the highest levels of expression both in vitro and in
      vivo. P(A) sequences were found to have significant effects on transgene
      expression. The effect of a multiple enhancer was also examined. Optimized
      plasmids of this study were pCASL3 (composed of CMV enhancer, beta-actin
      promoter, beta-actin intron, Simian virus (SV40) P(A) sequence and SV40 enhancer)
      and pCMVSL3 (composed of CMV enhancer, CMV promoter, intron A, SV40 P(A) sequence
      and SV40 enhancer). These comparative analyses could provide a systematic
      reference for the development of vector construction for gene therapy, vaccine
      development, and gene transfer experiments.

PMID- 11470521
TI  - A DNA polymorphism specific to Candida albicans strains exceptionally successful
      as human pathogens.
AB  - A large proportion of infection-causing isolates of the yeast Candida albicans
      belong to a general-purpose genotype, identifiable by fingerprinting with the
      moderately repetitive sequence Ca3. The high prevalence of this group -- up to
      70% in some patient categories -- suggests that its members possess genetic
      determinants, which enhance their success as pathogens compared to other strains.
      To find such determinants we are comparing the genomes of representatives of the
      general-purpose genotype cluster with the genomes of other strains. In this paper
      we describe the identification of a 985 bp HpaII fragment (MU13-4) specific to
      general-purpose genotype strains. The fragment was present in 90% of these
      strains, but only in 10% of other strains. The fragment did not hybridize with
      probe Ca3, used to define the general-purpose cluster. It contains elevated
      levels of repetitive DNA. Sequences homologous to MU13-4 are dispersed throughout
      the chromosomes of general-purpose strains but are rarer or absent in other
      strains, as judged by Southern hybridization. Using the Stanford C. albicans
      genome database, we have placed the MU13-4 fragment next to a CARE-1 element. We
      also found 79 significant homologies between parts of MU13-4 and 19 other
      contigs. Attempts to amplify the region surrounding the polymorphic fragment in
      non-general-purpose genotype strains suggest, as do the hybridization data, that
      the polymorphism is created by a deletion in non-cluster strains. These results
      show that it is possible to identify polymorphisms specific to general-purpose
      genotype strains. Primers against the fragment will allow PCR-based
      discrimination between general-purpose genotype strains and other strains,
      facilitating investigations aimed at determining morbidity and mortality caused
      by general-purpose genotype strains compared to other strains.

PMID- 11470522
TI  - Edited transcripts compete with unedited mRNAs for trans-acting editing factors
      in higher plant chloroplasts.
AB  - Chloroplast RNA transcripts of vascular plants undergo C to U editing at
      approximately 30 sites, but there is no consensus sequence that identifies a C to
      be edited. Both sequences closely surrounding an edited C and unidentified site
      specific trans-acting factors have been shown to be important for editing. The
      ability of an already edited transgenic sequence to bind and thus titrate a trans
      acting editing factor was evaluated for two editing sites, ndhF and rpoB site 2.
      The U-containing rpoB transcripts did not affect editing of the endogenous rpoB
      transcripts, likely because the comparable C-containing transcripts containing 27
      nucleotides surrounding the edited C were only 20% edited, indicating a low
      affinity of a trans-factor for this length of edited sequence. Surprisingly, U
      containing ndhF transgene transcripts reduced endogenous ndhF transcript editing
      to the same degree as a C-containing transgene transcript. This indicates that
      the C target of editing is not a critical recognition feature for the site
      specific trans-acting factor.

PMID- 11470523
TI  - Necdin acts as a transcriptional repressor that interacts with multiple guanosine
      clusters.
AB  - Necdin is a growth suppressor expressed predominantly in postmitotic neurons, and
      ectopic expression of this protein suppresses cell growth. Here we report that
      Necdin directly binds to specific DNA sequences and serves as a transcriptional
      repressor. Polyhistidine-tagged Necdin was used for selection of random-sequence
      oligonucleotides by polymerase chain reaction-based amplification. Necdin
      recognized guanosine (G)-rich sequences that encompass multiple G clusters and
      intervening mono- or di-nucleotides of A, T and C. These sequences, termed GN
      boxes, resemble multiply aligned forms of the canonical GC box which is
      recognized by Sp family members. Necdin directly bound to a GN box consisting of
      contiguous two GC boxes with four G clusters, but not to a single GC box with two
      G clusters, whereas Sp1 bound to both. In a reporter system using Drosophila
      Schneider Line 2 cells, Necdin repressed Sp1-dependent activity of mouse c-myc P1
      promoter that contains a typical GN box. Deletion of the GN box from the c-myc P1
      promoter or its conversion to the single GC box abolished the Necdin-dependent
      repression. These results suggest that Necdin modulates gene transcription via
      the GN box that is potentially recognized by GC box-targeting Sp family members.

PMID- 11470524
TI  - Characterization and expression of three forms of cDNA encoding chicken platelet
      derived growth factor-A chain.
AB  - Platelet-derived growth factor (PDGF) affects cell proliferation and
      differentiation during mammalian embryogenesis. In a number of avian species,
      PDGF-alpha receptors and PDGF-A chain (PDGF-A) are present during chicken limb
      and lens development. However, little is understood about the chicken PDGF-A
      gene. The present study identified short form type 1 (S1), long form (L) and
      short form type 2 (S2) cDNA clones encoding chicken PDGF-A chain (PDGF-A). These
      clones were isolated from a chicken hepatoma cell line (LMH) mRNA by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and cDNA library cloning.
      Genomic sequencing and Southern blotting revealed that these forms were generated
      by alternative splicing. The mRNAs of S1 and L contained two transcription start
      sites on one exon. At the amino acid level, the mature protein encoded by the L
      clone showed 90 and 85% homology with the processed coding regions of the long
      form of human and Xenopus PDGF-A, respectively. The putative mature peptides of
      all forms of chicken PDGF-A encompassed the eight cysteine residues conserved in
      all known forms of PDGF. We examined the expression of the three forms in chicken
      tissues and cells using RT-PCR. Expression of these forms varied among tissues
      and cells. Levels of PDGF mRNAs were very low in chicken thrombocytes, which are
      analogous to mammalian platelets. However, the level of PDGF-A chain mRNA
      expression in chicken thrombocytes peaked 4 h after exposure to type 1 collagen
      or thrombin, and then decreased gradually with continued incubation. These
      results suggest that chicken PDGF in thrombocytes plays an important role in the
      vascular system and in healing damaged tissue.

PMID- 11470525
TI  - Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1)
      by Sp1.
AB  - Oxysterol 7 alpha-hydroxylase catalyzes hydroxylation of oxysterols and
      neurosterols and plays a role in the alternative bile acid synthesis pathway.
      This gene is widely expressed in many organs and peripheral tissues and may
      protect tissues from the toxicity of oxysterols. Mutation in CYP7B1 caused
      neonatal cholestasis. To examine the regulatory mechanisms governing CYP7B1
      expression, the 5' flanking sequence of the CYP7B1 was analyzed and revealed a
      CpG island of about 1.2 kb. Transient transfection assays of deletion mutants of
      the CYP7B1 promoter-luciferase reporter gene in human liver-derived HepG2,
      fibroblast NT1088, and human embryonic kidney 293 cell lines revealed that the
      region from -291 to +189 was critical for gene transcription. Three GC box
      sequences located between -25 and +10 were essential for basal transcription
      because mutations of these sequences markedly reduced promoter activity. Sp1 and
      Sp3 bound to these sequences as demonstrated by DNase I footprinting assays and
      electrophoretic mobility shift assay. Thus, regulation of CYP7B1 transcription by
      Sp1 may play a pivotal role in regulating oxysterol levels, which regulate
      cholesterol metabolism.

PMID- 11470526
TI  - DNA (cytosine-5) methyltransferase turnover and cellular localization in
      developing Paracentrotus lividus sea urchin embryo.
AB  - The turnover and localization of the enzyme DNA (cytosine-5) methyltransferase
      (Dnmt1) were studied during Paracentrotus lividus sea urchin embryo development
      using antibody preparations against the NH(2) and COOH-terminal regions of the
      molecule. The antibodies reveal, by Western blots and whole-mount analyses, that
      the enzyme is differently required during embryonic development. The changeover
      point is at blastula stage, where a proteolytic mechanism hydrolyses the enzyme
      present in all embryonic cells by removing a peptide of about 45 kDa from the
      amino terminal region of the 190 kDa enzyme initially synthesized on maternal
      transcripts. The resulting 145 kDa enzyme shows modified catalytic properties,
      different antibody reactivity and is rapidly destroyed in the few hours before
      gastrulation. At more advanced stages of development the enzyme is newly
      synthesized but only in particular cell types, among which neurons. The data show
      that Dnmt1 is removed from embryonic cells before gastrulation to be synthesized
      again at different levels in different cell types, indicating that the
      concentration of Dnmt1 is critical for the various differentiated cells of the
      developing sea urchin embryo.

PMID- 11470527
TI  - Unusual organization of a developmentally regulated mitochondrial RNA polymerase
      (TBMTRNAP) gene in Trypanosoma brucei.
AB  - We report here the characterization of a developmentally regulated mitochondrial
      RNA polymerase transcript in the parasitic protozoan, Trypanosoma brucei. The
      3822 bp protein-coding region of the T. brucei mitochondrial RNA polymerase
      (TBMTRNAP) gene is predicted to encode a 1274 amino acid polypeptide, the
      carboxyl-terminal domain of which exhibits 29-37% identity with the mitochondrial
      RNA polymerases from other organisms in the molecular databases. Interestingly,
      the TBMTRNAP mRNA is one of several mature mRNA species post-transcriptionally
      processed from a stable, polycistronic precursor. Alternative polyadenylation of
      the TBMTRNAP mRNA produces two mature transcripts that differ by 500 nt and that
      show stage-specific differences in abundance during the T. brucei life cycle.
      This alternative polyadenylation event appears to be accompanied by the
      alternative splicing of a high abundance, non-coding downstream transcript of
      unknown function. Our finding that the TBMTRNAP gene is transcribed into two
      distinct mRNAs subject to differential regulation during the T. brucei life cycle
      suggests that mitochondrial differentiation might be achieved in part through the
      regulated expression of this gene.

PMID- 11470528
TI  - Molecular characterization of CLPT1, a SEC4-like Rab/GTPase of the
      phytopathogenic fungus Colletotrichum lindemuthianum which is regulated by the
      carbon source.
AB  - The gene CLPT1 (Colletotrichum lindemuthianum Protein Transport 1) encoding a
      Rab/GTPase was isolated from the filamentous fungus Colletotrichum
      lindemuthianum, the causal agent of bean anthracnose. At the amino acid level,
      CLPT1 shows between 54 and 80% identity to SEC4-like proteins, a class of
      molecules required for intracellular vesicular transport in yeasts. In
      particular, typical SEC4 domains involved in nucleotide binding and membrane
      attachment are present in the CLPT1 sequence. Functional identity of CLPT1 with
      SEC4 was confirmed by complementation of the Saccharomyces cerevisiae sec4-8
      mutation. This is the first report of a gene involved in the control of
      intracellular vesicular trafficking in a phytopathogenic fungus. RNA blot
      analyses of CLPT1 expression were performed during in vitro growth of the fungus
      on synthetic media containing glucose or pectin, as single carbon source. The
      accumulation of CLPT1 mRNA was strongly increased on pectin, a plant cell wall
      polysaccharide that induces the production of extracellular pectinases, whereas
      the level of CLPT1 mRNA was below the detection threshold on glucose. These
      results suggest that CLPT1 is mainly involved in protein secretion and that the
      production of extracellular enzymes potentially involved in pathogenesis in
      filamentous fungi is sustained by induction of the genes involved in the
      secretory machinery.

PMID- 11470529
TI  - Cell toxicity caused by products of the p(L) operon of bacteriophage lambda.
AB  - Induction of a lambda prophage causes the death of the host cell even in the
      absence of phage replication and lytic functions due to expression of functions
      from the lambda p(L) operon. We genetically modified the lambda prophage to
      determine which lambda p(L) operon functions were involved in cell killing.
      Viability assays and flow cytometry were used to monitor cell death and
      filamentation. The kil gene was shown to cause cell death and filamentation as
      described previously. Another killing activity was mapped within the p(L) operon
      to the gam gene. Inspection of the DNA sequence showed that there are two
      possible translation start points for both kil and gam. In both cases, the
      shorter of the two possible products could cause cell killing. The shorter
      products were also sufficient for the known filamentation and recombination
      activities of the respective Kil and Gam functions. The expression level of the
      p(L) operon is down-regulated by Cro repressor. In the absence of Cro, higher
      p(L) expression levels allow either Kil or Gam to be lethal or growth inhibitory,
      whereas at lowered expression in Cro-repressed conditions, only Kil is lethal.
      The filamentation function of Kil and recombination activity of Gam are
      unaffected at Cro-repressed levels of expression.

PMID- 11470530
TI  - Developmentally-regulated interaction of a transcription factor complex
      containing CDP/cut with the early histone H3 gene promoter of the sea urchin
      Tetrapygus niger is associated with changes in chromatin structure and gene
      expression.
AB  - During sea urchin embryogenesis the early histone genes are temporally expressed
      to accommodate the high demand for histone proteins during DNA replication at
      early cleavage stages of development. The early histone genes are
      transcriptionally active from the 16-cell stage, reaching a peak in expression at
      the 128-cell stage that gradually decreases until expression is completely
      inhibited at the late blastula stage. We are studying the gene regulatory
      mechanisms that control early histone gene expression in sea urchins to
      understand the interrelationships between chromatin remodeling and
      transcriptional activation during development. Here, we have investigated
      chromatin organization and transcription factor interactions by analyzing
      nuclease hypersensitivity and protein binding in the promoter region of the early
      histone H3 gene from the sea urchin Tetrapygus niger. We have found a DNase I
      hypersensitive domain centered at -90 in the early histone H3 gene promoter which
      is only detected in embryos at the 128-cell stage expressing high levels of early
      histone H3 mRNA. This hypersensitive site (-110 to -70) encompasses two
      regulatory elements (TnH3NFH3.1 and TnH3CCAAT). The -94 to -77 region of the
      histone H3 promoter is recognized by a transcription factor complex in nuclear
      extracts from 128-cell embryos. Methylation interference analysis and competition
      studies demonstrated a specific interaction at the CCAAT sequence. Using specific
      antibodies we find that the homeodomain transcription factor CDP/cut is the DNA
      binding component of the complex interacting with the early histone H3 gene
      promoter in T. niger. Our results provide further evidence for the functional
      role of CDP/cut in developmental regulation of histone gene expression in
      phylogenetically diverse eukaryotic species.

PMID- 11470531
TI  - Positive-negative selection for homologous recombination in Arabidopsis.
AB  - In plants gene knock-outs and targeted mutational analyses are hampered by the
      inefficiency of homologous recombination. We have developed a strategy to enrich
      for rare events of homologous recombination in Arabidopsis using combined
      positive and negative selection. The T-DNA targeting construct contained two
      flanking regions of the target alcohol dehydrogenase gene as homologous
      sequences, and neomycin phosphotransferase and cytosine deaminase as positive and
      negative markers, respectively. A root explant transformation procedure was used
      to obtain transgenic calli. Among 6250 transformants isolated by positive
      selection, 39 were found to be resistant to negative selection as well. Of these
      39, at least one had undergone homologous recombination correlated with a
      unidirectional transfer of information. Although the ADH locus was not changed,
      our data demonstrate that a homologous recombination event can be selected by
      positive negative selection in plants.

PMID- 11470532
TI  - CYP9E2, CYP4C21 and related pseudogenes from German cockroaches, Blattella
      germanica: implications for molecular evolution, expression studies and
      nomenclature of P450s.
AB  - The cDNAs of two novel P450s (CYP9E2 and CYP4C21) were isolated from German
      cockroaches, Blattella germanica. Both CYP9E2 and CYP4C21 are typical microsomal
      P450s and their deduced amino acid sequences share a number of common
      characteristics with other members of the P450 superfamily. Northern blot
      analyses using a CYP9E2 or CYP4C21 probe showed that 'CYP9E2' and 'CYP4C21' were
      expressed at all life stages. Two pseudogenes related to CYP9E2 and three
      pseudogenes related to CYP4C21 were also isolated. These represent the first P450
      pseudogenes from an insect other than Drosophila melanogaster. The relative
      number of P450 pseudogenes in B. germanica is apparently higher than in D.
      melanogaster. The implications of these results for the molecular evolution,
      expression studies and nomenclature of P450s are discussed.

PMID- 11470533
TI  - In vitro selection of enzymatically active lipase variants from phage libraries
      using a mechanism-based inhibitor.
AB  - The 'detergent lipase' Lipolase, from Thermomyces lanuginosa was subjected to a
      combinatorial protein engineering/phage display approach with the aim of
      identifying new enzyme variants with improved characteristics in the presence of
      detergents. First it was demonstrated that wild-type Lipolase could be produced
      in Escherichia coli retaining full activity and be displayed as an active enzyme
      fused to coat protein 3 on E. coli phage M13. A phagemid library designed to
      result in approximately two to three mutations per lipase gene was then
      constructed. Nine amino acids located in two regions close to the active site
      were targeted for randomization. Selections using a mechanism-based biotinylated
      inhibitor showed that phages displaying Lipolase could be specifically enriched
      from a population of control phages. Selections on a library phage stock in the
      presence of inhibitor and a commercial powder detergent resulted in a step-wise
      increase in the proportion of active clones. Analysis of 84 active clones
      revealed that they all expressed lipase activity, but with lower activities than
      that of a wild-type Lipolase-producing clone. In six of the seven most active
      clones a wild-type serine at position 83 had been replaced by threonine, a
      substitution known to alter the substrate chain length preference of Lipolase
      variants. Furthermore, the selection had enriched enzyme variants with a high
      degree of conservatism in one of the variegated regions, suggesting that this
      region is important for enzymatic activity and that the designed selection
      procedure was relevant. The selected variants contained primarily basic amino
      acid residues within the other variegated region. Taken together, the described
      results show that selection protocols based on enzymatic activity can be designed
      for this enzyme class which should be of importance for future protein
      engineering attempts.

PMID- 11470534
TI  - Phylogenetic relationship and mode of evolution of yeast DNA topoisomerase II
      gene in the pathogenic Candida species.
AB  - We have determined the nucleotide sequences of about 55% of the region of the DNA
      topoisomerase II gene (approximately 2.3 kb) isolated from the pathogenic Candida
      species, C. dubliniensis, C. parapsilosis, C. tropicalis, C. krusei, C. kefyr, C.
      guilliermondii and C. lusitaniae. Evolutionary relationships among nine Candida
      species including those of C. albicans and C. glabrata were studied based on the
      DNA topoisomerase II gene. The nucleotide sequences of 2192 bp, which covered two
      catalytic domains, ATPase and cutting/resealing, were subjected to phylogenetic
      analysis. Sequence comparison and evolutionary analysis have revealed that the
      Candida species tested here are not monophyletic, and the two strains within the
      species C. tropicalis and C. parapsilosis are too diverse to be in a single
      species. A wide variety of divergence was observed among the functional domains
      of DNA topoisomerase II, suggesting that Candida species were in different
      evolutionary paths at least as regarding the DNA topoisomerase II gene. Sequence
      information and the observation on the species-specific manner of molecular
      evolution of DNA topoisomerase II in Candida will be applied to develop a method
      of identification and characterization of the Candida species in both natural and
      clinical isolates.

PMID- 11470535
TI  - Generation of a P1 artificial chromosome library of the Southern pufferfish.
AB  - We describe the generation of a P1 artificial chromosome genomic library from the
      Southern pufferfish, Spheroides nephelus. The arrayed library consists of
      approximately 30,000 clones and has an average insert size of 125-150 kb. The
      coverage is estimated to encompass seven to eight genome equivalents. The library
      has been used for isolating numerous genomic clones and for establishing contigs
      of several multigene families. Analysis of several of the clones from this
      library suggests a preponderance of CA repeat tracts relative to their abundance
      in humans. The library and high-density filters have been made available to the
      scientific public through genomics distribution companies.

PMID- 11470536
TI  - Genomic organization and chromosomal localization of the Asna1 gene, a mouse
      homologue of a bacterial arsenic-translocating ATPase gene.
AB  - The plasmid encoded ArsA ATPase in Escherichia coli is the catalytic component of
      an oxyanion pump that is responsible for resistance to arsenicals and
      antimonials. Arsenite or antimonite allosterically activates the ArsA ATPase
      activity. In this paper, we report the cloning and characterization of the mouse
      homologue (Asna1) of the bacterial arsA gene. The Asna1 gene encodes an open
      reading frame of 348 amino acids and exhibits 27% identity to the bacterial ArsA
      protein and 99% similarity to its human counterpart (hASNA-1). The Asna1 mRNA is
      a approximately 1.3 kb transcript and is present at high levels in kidney and
      testis, moderate levels in brain, liver, lung and skin, and low levels in heart,
      small intestine, spleen, stomach, and thymus. A negligible amount of Asna1
      transcript is detected in skeletal muscle. We have also characterized the genomic
      structure of the Asna1 gene. The gene spans over 7 kb and consists of seven exons
      and six introns. All splice sites conform to the GT-AG rule, except for the
      splice donor site of intron 4 that is GC instead of GT. Fluorescence in situ
      hybridization indicates that the Asna1 gene is localized in the C3-D1 region of
      mouse chromosome 8.

PMID- 11470537
TI  - Germline and somatic mutations in hMSH6 and hMSH3 in gastrointestinal cancers of
      the microsatellite mutator phenotype.
AB  - Hereditary and sporadic gastrointestinal cancer of the microsatellite mutator
      phenotype (MMP) is characterized by a remarkable genomic instability at simple
      repeated sequences. The genomic instability is often caused by germline and
      somatic mutations in DNA mismatch repair (MMR) genes hMSH2 and hMLH1. The MMP can
      be also caused by epigenetic inactivation of hMLH1. The MMP generates many
      somatic frameshift mutations in genes containing mononucleotide repeats. We
      previously reported that in MMP tumors the hMSH6 and hMSH3 MMR genes often carry
      frameshift mutations in their (C)(8) and (A)(8) tracks, respectively. We proposed
      that these 'secondary mutator mutations' contribute to a gradual manifestation of
      the MMP. Here we report the detection of other frameshift, nonsense, and missense
      mutations in these genes in colon and gastric cancers of the MMP. A germline
      frameshift mutation was found in hMSH6 in a colon tumor harboring another somatic
      frameshift mutation. Several germline sequence variants and somatic missense
      mutations at conserved residues were detected in hMSH6 and only one was detected
      in hMSH3. Of the three hMSH6 germline variants in conserved residues, one
      coexisted with a somatic mutation at the (C)(8) track and another had a somatic
      missense mutation. We suggest that some of these germline and somatic missense
      variants are pathogenic. While biallelic hMSH6 and hMSH3 frameshift mutations
      were found in some tumors, many tumors seemed to contain only monoallelic
      mutations. In some tumors, these somatic monoallelic frameshift mutations at the
      (C)(8) and (A)(8) tracks were found to coexist with other somatic mutations in
      the other allele, supporting their functionality during tumorigenesis. However,
      the low incidence of these additional somatic mutations in hMSH6 and hMSH3 leaves
      many tumors with only monoallelic mutations. The impact of the frameshift
      mutations in gene expression was studied by comparative analysis of RNA and
      protein expression in different tumor cell clones with different genotypes. The
      results show that the hMSH6 (C)(8) frameshift mutation abolishes protein
      expression, ruling out a dominant negative effect by a truncated protein. We
      suggest the functionality of these secondary monoallelic mutator mutations in the
      context of an accumulative haploinsufficiency model.

PMID- 11470538
TI  - The gene structure of the Drosophila melanogaster homolog of the human proto
      oncogene fos.
AB  - The Drosophila melanogaster homolog of the human proto-oncogene fos is Dfos. It
      is the only fos homolog in the Drosophila genome. Fos functions as a subunit of
      the heterodimeric transcription factor AP-1. There are two models of the Dfos
      gene. The first comes from a cDNA sequence of Dfos (Perkins et al., Genes Dev. 4
      (1990) 822). The second is from the gene sequence published by the Drosophila
      genome project (Adams et al., Science 287 (2000) 2185), and there are notable
      contradictions between the two models. The promoter and the 5' end of the
      transcript sequence were not identified in either model. In this paper, we
      present the gene structure of Dfos and identify the promoter. This promoter has
      an initiator and a downstream promoter element sequence, but lacks a TATA box.
      Through comparison of the mRNA and genomic DNA sequences, three introns varying
      in length from 66 bp to 17.57 kb were found and verified by RT-PCR. The Dfos gene
      is 21.2 kb in length, giving a transcript of 3438 bp, coding for a predicted
      protein of 595 amino acids. The 3' untranslated region is confirmed to be 1092 bp
      in length.

PMID- 11470539
TI  - Molecular cloning and characterization of the DNA mismatch repair gene class 2
      from the Trypanosoma cruzi.
AB  - Genes with homology to the bacterial mutS gene, which encodes a protein involved
      in post-replication DNA mismatch repair, are known in several organisms. Using a
      degenerate PCR strategy, we cloned a Trypanosoma cruzi genomic DNA fragment
      homologous to the mutS gene class two (MSH2). This fragment was used as a probe
      to select the corresponding cDNAs from a T. cruzi cDNA library. The complete
      sequence of the gene (3304 bp), denominated TcMSH2, was obtained. The sequence
      contained an open reading frame of 2889 bp coding for a putative protein of 962
      amino acids. Computational analyses of the amino acid sequence showed 36%
      identity with MSH2 proteins from other eukaryotes and revealed the presence of
      all functional domains of MutS proteins. Hybridization analyses indicated that
      the TcMSH2 gene is present as a single copy gene that is expressed in all forms
      of the T. cruzi life cycle. The role of the product of the TcMSH2 gene in
      mismatch repair was investigated by negative dominance phenotype analyses in
      Escherichia coli. When eukaryotic muts genes are expressed in a prokaryotic
      system, they increase the bacterial mutation rate. The same phenomenon was
      observed with the TcMSH2 cDNA, indicating that T. cruzi MSH2 interferes with the
      bacterial mismatch system. Phylogenetic analyses showed that the T. cruzi gene
      grouped with the MSH2 clade confirming the nature of the gene isolated in this
      work.

PMID- 11470540
TI  - Two types of replication protein A 70 kDa subunit in rice, Oryza sativa:
      molecular cloning, characterization, and cellular & tissue distribution.
AB  - Replication protein A (RPA), which is comprised of three subunits, is an
      important factor involved in DNA replication, repair, and transcription. We
      isolated and characterized 70 and 32 kDa subunits of RPA from rice (Oryza sativa
      cv. Nipponbare) termed OsRPA70a and OsRPA32. OsRPA70a shows a low level of
      homology with OsRPA1 which was isolated from deepwater rice (Oryza sativa cv. Pin
      Gaew 56), previously. We also succeeded to isolate OsRPA70b which is homologue to
      OsRPA1 from Oryza sativa cv. Nipponbare. OsRPA70a shows only 33.8% sequence
      identity with OsRPA70b, indicating that two different types of 70 kDa RPA
      subunits are present in Oryza sativa cv. Nipponbare. These subunits showed
      differences in their expression patterns among tissues. The transcripts of
      OsRPA70a and OsRPA32 were expressed strongly in proliferating tissues such as
      root tips and young leaves that contain root apical meristem and marginal
      meristem, respectively, and weakly in the mature leaves which have no
      proliferating tissues. On the other hand, OsRPA70b was expressed mostly in the
      proliferating tissues. The roles of these molecules in plant DNA replication and
      DNA repair are discussed.

PMID- 11470542
TI  - Seroepidemiological survey of distemper virus infection in the Caspian Sea and in
      Lake Baikal.
AB  - Forty Caspian seals were surveyed seroepidemiologically between 1993 and 1998
      around the times of mass mortality that occurred in 1997 in the Caspian Sea and
      seven Baikal seals were also surveyed in 1998. Virus neutralizing tests and ELISA
      clearly suggested that distemper virus epidemic was caused in Caspian seals
      before the spring of 1997 and that CDV infection continued to occur in Lake
      Baikal in recent years.

PMID- 11470543
TI  - Establishment of latency associated with glycoprotein E (gE) seroconversion after
      bovine herpesvirus 1 infection in calves with high levels of passive antibodies
      lacking gE antibodies.
AB  - This study was conducted to investigate the glycoprotein E (gE) antibody response
      raised after inoculation with a low infectious dose of bovine herpesvirus 1 (BHV
      1) in six calves possessing high levels of passive immunity from cows repeatedly
      vaccinated with gE deleted marker vaccine. Four out of the six calves developed
      gE antibodies 3-5 weeks after infection, whereas the two other ones remained
      seronegative to gE. After 5 months of infection, the six calves were treated with
      dexamethasone. Virus was only re-excreted by the four calves which previously
      seroconverted against gE. The two other calves became seronegative against BHV-1,
      30-32 weeks after infection. A second dexamethasone treatment performed 11 months
      after infection failed to demonstrate a latent infection in these two calves.
      Moreover, the lack of identification of a cell-mediated immune response, after
      the two dexamethasone treatments, and the failure to detect BHV-1 DNA sequences
      in trigeminal ganglia strongly suggest that these two calves were not latently
      infected. In conclusion, the presence of high levels of maternal immunity lacking
      gE antibodies does not prevent latency after infection with a low titre of BHV-1.
      Moreover, latency is associated with a serological response to gE. These results
      confirm that the gE deletion is a good marker to identify young calves latently
      infected with a field virus.

PMID- 11470544
TI  - Comparative studies of the persistence of animal mycoplasmas under different
      environmental conditions.
AB  - A comparison of the persistence of mycoplasmas in animals was carried out. When
      inoculated into liquid media, strains of Mycoplasma bovis, M. arginini,
      Acholeplasma laidlawii, and A. axanthum persisted for 59-185 days post
      inoculation. The survival periods were not significantly influenced by
      temperature (4, 30, 37 degrees C, and room temperature). The survival periods for
      M. bovigenitalium, M. gallisepticum, M. bovirhinis, and M. gateae ranged from <7
      to 185 days depending on medium components and temperature. Further, it was
      determined that strains of M. bovigenitalium, M. bovis, M. bovirhinis, M.
      arginini, and A. laidlawii persisted in a dry paper disc for at most 28, 126,
      154, 56 and over >168 days at 4 degrees C, respectively. At 4 degrees C, strains
      of M. gallisepticum, M. columborale, M. edwardii, M. felis, and M. gateae
      survived for at most 28, 21, 42, 28, 28 and 70 days, respectively. At 30 degrees
      C, strains of M. bovis, M. bovirhinis, M. arginini, A. laidlawii, and M.
      gallisepticum persisted for at most 28, 84, 56, >168 and 14 days, respectively,
      but strains of M. gallisepticum, M. columborale, M. edwardii, M. felis, M.
      gateae, and U. diversum did not survive for more than 14 days. In an outdoor
      environment, strains of M. bovirhinis and A. laidlawii survived for at most 28
      and 14 days, respectively. Finally, it was found that 14 isolates of M.
      gallisepticum persisted for periods similar to those of the reference strains.
      The results under dry conditions at a variety of temperatures presented
      contribute to understanding the epizootiology of mycoplasmal infections in the
      field.

PMID- 11470545
TI  - An epidemiological study of Salmonella enterica serovar 4, 12:b:- in broiler
      chickens in Denmark.
AB  - Epidemiological investigations of isolates of Salmonella enterica serovar 4,
      12:b:- were carried out to establish particular molecular markers to assign
      isolates to a common origin. Plasmid profiling demonstrated that over 50% of 291
      isolates, obtained between 1991 and 1996, were plasmid-free. The remaining
      isolates exhibited a common trend in plasmid content of 105 and 2kb. Although no
      specific correlation to any particular source within the poultry industry was
      discernible using plasmid analysis, there were indications of clonality with
      local divergence. Ribotyping with EcoRI demonstrated limited discriminative
      potential as 96% of the isolates expressed a common profile. Ribotyping with
      HindIII failed to further differentiate the isolates. IS200 (PstI) typing and
      PFGE (NotI and XbaI) afforded some degree of further discrimination with selected
      isolates. Each technique produced four profiles, but dominant profiles were also
      apparent. Eighteen variables were selected for multivariate logistic regression
      analysis in order to identify risk areas associated with broiler flocks within
      the industry. An increased risk for S. 4, 12:b:- infection was only associated
      with the feedmills used. Random effects at the house and/or farm level were also
      found to be statistically significant. Of the 16 feedmills associated with the
      isolation of 4, 12:b:-, six were deemed to be significant risk factors.

PMID- 11470546
TI  - Development of an ELISA procedure to detect swine carriers of pathogenic Yersinia
      enterocolitica.
AB  - An enzyme immunoassay (ELISA) was developed to detect antibodies in pigs against
      the lipopolysaccharidic antigen of the three serotypes of Yersinia enterocolitica
      mostly associated with human infections. Recent epidemiological evidence has
      demonstrated that pigs and pork are important sources of yersiniosis in humans.
      The purpose of this study was to clarify the use of an ELISA to detect swine
      carriers of this enteroinvasive bacteria by examining seroconversion and tissue
      distribution of Y. enterocolitica following experimental infection and then
      screening pigs at a slaughterhouse by bacterial culture and ELISA. It was
      observed that seroconversion occurred in animals experimentally inoculated with
      Y. enterocolitica but not with other enterobacteria. It was also found that 27%
      of swine at a slaughterhouse carried the bacterium in their tonsils and/or
      intestinal tract, whereas 66% showed serological evidence of previous infection.
      About 6% of swine at slaughter were culture-positive, but seronegative. Although,
      similar numbers of swine showed serological evidence of previous infection by
      each of the three Y. enterocolitica serotypes tested, virtually all culture
      isolates belonged to serotype O:3. This ELISA appears as a valuable control tool
      that can be used, in conjunction with culture, to identify pigs or herds infected
      by strains of Y. enterocolitica associated with human infections.

PMID- 11470547
TI  - Molecular characterization of the pore-forming toxin, pyolysin, a major virulence
      determinant of Arcanobacterium pyogenes.
AB  - Arcanobacterium pyogenes is a common inhabitant and opportunistic pathogen of
      domestic animals. The pathogenesis of this organism in a range of suppurative
      diseases is not well understood. However, the development of genetic techniques
      to study this organism has allowed advances in the analysis of A. pyogenes
      virulence factors. A major step in this analysis was the identification and
      cloning of the A. pyogenes hemolytic exotoxin, pyolysin (PLO). PLO is the most
      divergent member of the cholesterol-binding pore-forming family of toxins. PLO is
      also divergent in a C-terminal undecapeptide motif which is almost invariant
      among other members of the family. This divergent undecapeptide motif is required
      for the full cytolytic activity of PLO and is also responsible for its oxygen
      resistant nature. Insertional inactivation of the plo gene results in a
      significant reduction in virulence in an intraperitoneal mouse model of
      infection. The virulence of the plo mutant can be restored by providing PLO in
      trans, suggesting that PLO is a major virulence factor in A. pyogenes
      pathogenesis in mice. Results of previous vaccination trials with crude antigens
      against A. pyogenes infection in domestic animals and mice have been equivocal at
      best. However, a recombinant PLO-based subunit vaccine protected mice from
      experimental A. pyogenes infection, indicating that PLO is also an important host
      protective antigen. These results provide promise that the dogma that domestic
      animals are recalcitrant to vaccination against A. pyogenes infection may prove
      false.

PMID- 11470548
TI  - Detection and characterization of Shiga toxin-producing Escherichia coli in feral
      pigeons.
AB  - Escherichia coli strains producing a variant of Shiga toxin 2 (Stx2), designated
      Stx2f, have been recently described in the stools of feral pigeons. During 1997
      1998, 649 pigeons were trapped and examined in three different squares of Rome.
      Stool samples were collected from each bird and enrichment cultures were examined
      for the presence of Stx by the vero cell assay. Stx-producing E. coli (STEC) were
      isolated from the positive cultures and characterized by serotyping and PCR
      analysis of stx and other virulence-related genes. Stx was detected in 10.8% of
      the stool enrichment cultures. The percentage of positive birds did not differ
      significantly for the three flocks considered and the season of sample
      collection. Conversely, STEC carriage was significantly more frequent in young
      than in adult birds (17.9 versus 8.2%). None of the birds examined showed signs
      of disease. STEC strains were isolated from 30 of 42 Stx-positive cultures
      examined. All the strains produced Stx2f, and most of them possessed genes
      encoding for intimin and the cytolethal distending toxin (CLDT). Six serogroups
      were identified, but most of the isolates belonged to O45, O18ab, and O75.
      Molecular typing indicated that most of the isolates within a flock were clonally
      related. This work confirms that pigeons represent a natural reservoir of STEC
      strains characterized by the production of the toxin variant Stx2f, and by the
      frequent presence of eae and cldt genes. Further work is needed to clarify
      whether these STEC may represent a cause of avian disease or even a potential
      health hazard for humans.

PMID- 11470549
TI  - Experimental infection of pregnant ewes with enteric and abortion-source
      Chlamydophila abortus.
AB  - Two groups of pregnant ewes were experimentally infected oronasally in
      midpregnancy. A faecal and an abortion-source isolate of Chlamydophila abortus
      were used. They were derived from a healthy ewe from a flock with no history of
      abortion, and from an aborted foetus in a farm with enzootic abortion. As
      assessed by modified Ziehl-Neelsen (MZN) staining, egg culture, antigen ELISA,
      the Clearview test and immunohistochemistry, inoculation resulted in placental
      and/or foetal infection in all ewes. Histopathology revealed placentitis in two
      and four ewes inoculated with the enteric or abortion-source isolate,
      respectively, in addition, these samples were immunohistochemically positive for
      chlamydial antigen. All six ewes infected with the enteric isolate and five of
      seven ewes infected with the abortion-source isolate showed evidence for a
      serological response by an indirect ELISA or CFT. Neither chlamydiae nor lesions
      were detected in the placentae and lambs of the uninfected control ewes, which
      remained seronegative. Our results suggest that enteric C. abortus can be
      associated with placental and foetal lesions in sheep.

PMID- 11470551
TI  - Chemical neuroanatomy of the basal ganglia--normal and in Parkinson's disease.

PMID- 11470552
TI  - Ionotropic and metabotropic GABA and glutamate receptors in primate basal
      ganglia.
AB  - The functions of glutamate and GABA in the CNS are mediated by ionotropic and
      metabotropic, G protein-coupled, receptors. Both receptor families are widely
      expressed in basal ganglia structures in primates and nonprimates. The recent
      development of highly specific antibodies and/or cDNA probes allowed the better
      characterization of the cellular localization of various GABA and glutamate
      receptor subtypes in the primate basal ganglia. Furthermore, the use of high
      resolution immunogold techniques at the electron microscopic level led to major
      breakthroughs in our understanding of the subsynaptic and subcellular
      localization of these receptors in primates. In this review, we will provide a
      detailed account of the current knowledge of the localization of these receptors
      in the basal ganglia of humans and monkeys.

PMID- 11470553
TI  - Oxidative metabolism and the detection of neuronal activation via imaging.
AB  - Recent years have witnessed a great growth of interest in non-invasive imaging
      methods, such as functional magnetic resonance imaging (fMRI) and positron
      emission tomography (PET), permitting identification of brain structures that
      mediate specific cognitive and behavioural tasks in humans. Because these
      techniques use physiological responses such as increased perfusion or metabolism
      as surrogate indicators of evoked neuronal electrical activity, understanding the
      role of these processes in sustaining the information processing function of
      neurons is vital to the proper interpretation of functional neuroimaging data. An
      ultimate goal of these non-invasive techniques is to approach the sensitivity and
      spatial resolution of earlier autoradiographic methods, which have repeatedly
      demonstrated exquisitely detailed delineations of neuronal response patterns
      using metabolic glucose uptake as a physiological tag. Although glucose is
      generally metabolized in conjunction with oxygen, technical challenges in imaging
      tissue oxygen consumption in vivo have limited the use of this complementary
      process in the detection of neuronal activation. In this article we review
      concepts linking cerebral blood flow and metabolism to neuronal activation, and
      compare functional imaging techniques that exploit these relationships. We also
      describe recently introduced MRI based methods for measurement of oxygen
      consumption and assess the relative contributions of different metabolic pathways
      during neuronal activation. Our calculations suggest that the bulk of the energy
      demand evoked during stimulation of neurons in visual cortex is met through
      oxidative metabolism of glucose, supporting the use of oxygen uptake as a marker
      for increased neuronal electrical activity.

PMID- 11470554
TI  - Cholinergic systems and schizophrenia: primary pathology or epiphenomena?
AB  - Post mortem schizophrenia research has been driven first by the dopamine and then
      the glutamate hypotheses. These hypotheses posit primary pathology in pathways
      dependent upon dopamine or glutamate neurotransmission. Although the dopamine and
      glutamate hypotheses retain considerable theoretical strength, neurobiological
      findings of altered dopamine or glutamate activity in schizophrenia do not
      explain all features of this disorder. A more synthetic approach would suggest
      that focal pathological change in either the prefrontal cortex or mesial temporal
      lobe leads to neurochemical changes in multiple neurotransmitter systems. Despite
      the limited experimental evidence for abnormal cholinergic neurotransmission in
      psychiatric disorders, increased understanding of the role of acetylcholine in
      the human brain and its relationship to other neurotransmitter systems has led to
      a rapidly growing interest in the cholinergic system in schizophrenia. This
      review focuses on the basic anatomy of the mammalian cholinergic system, and its
      possible involvement in the neurobiology of schizophrenia. Summaries of
      cholinergic cell groups, projection pathways, and receptor systems, in the
      primate and human brain, are followed by a brief discussion of the functional
      correlations between aberrant cholinergic neurotransmission and the signs and
      symptoms of schizophrenia.

PMID- 11470555
TI  - Accumulation of C-terminally truncated tau protein associated with vulnerability
      of the perforant pathway in early stages of neurofibrillary pathology in
      Alzheimer's disease.
AB  - Neurofibrillary pathology is a characteristic hallmark of Alzheimer's disease
      that is closely correlated with cognitive decline. We have analysed the density
      and distribution of neurofibrillary tangles (NFTs) that are immunoreactive with
      the monoclonal antibody (mAb) 423 in a prospectively analysed population of
      Alzheimer's disease (AD) cases and age-matched controls. NFTs were examined in
      allocortical and isocortical areas and correlated with Braak pathological stage
      and clinical severity of dementia. The mAb 423 was used as it recognises a C
      terminally truncated tau fragment that is a major constituent of NFTs. Our
      results show that extracellular NFTs and, to a lesser extent, intracellular NFTs,
      correlated significantly with both Braak stages and the clinical index of
      severity. Furthermore, a differential distribution of the two types of tangles
      indicates that layer II of the entorhinal cortex and the transentorhinal area are
      particularly vulnerable to neurofibrillary degeneration. These areas serve as a
      point of connection between isocortex and hippocampus. Our findings, therefore,
      suggest that the perforant pathway may be substantially affected by the
      accumulation of truncated tau protein in AD and that this represents a
      neuropathological predictor for the clinical severity of dementia. When
      neurofibrillary pathology was examined by combined labelling with mAbs 423 and
      Alz-50 and the dye thiazin red, we were able to demonstrate various stages of tau
      aggregation. The different stages may represent a sequence of conformational
      changes that tau proteins undergo during tangle formation in the allocortex
      during the early development of dementia in AD.

PMID- 11470556
TI  - Gene expression profiling in the post-mortem human brain--no cause for dismay.
AB  - Global expression profiling techniques such as microarray technology promise to
      revolutionize biology. Soon it will be possible to investigate alterations at the
      transcript level of the entire human genome. There is great hope that these
      techniques will at last shed light on the pathological processes involved in
      complex neuropsychiatric disorders such as schizophrenia. These scientific
      advances in turn have re-kindled a great interest and demand for post-mortem
      brain tissue. Good quality post-mortem tissue undoubtedly is the fundamental
      prerequisite to investigate complex brain disorders with molecular profiling
      techniques. In this review we show that post-mortem brain tissue can yield good
      quality mRNA and intact protein antigens which allow the successful application
      of traditional molecular biology methods as well as novel profiling techniques.
      We also consider the use of laser-capture microdissection on post-mortem tissue.
      This recently developed technique allows the experimenter to explore the
      molecular basis of cellular function at the single cell level. The combination of
      laser-capture microdissection with high throughput profiling techniques offers
      opportunities to obtain precise genetic fingerprints of individual neurons
      allowing comparisons of normal and pathological states.

PMID- 11470557
TI  - GABAergic neuronal subtypes in the human frontal cortex--development and deficits
      in schizophrenia.
AB  - Recent studies have provided evidence for a deficit of GABA-containing
      interneurons in the frontal cortex in schizophrenia. That this deficit might be
      brought about during early foetal or neonatal life is a hypothesis consistent
      with the substantial indications for a neurodevelopmental aetiology of the
      disease. GABAergic neurons can be defined by the presence of one of three types
      of calcium binding proteins, which are thought to have neuroprotective
      properties. We have undertaken an investigation into the postnatal ontology of
      these neuronal subtypes and find that calretinin expression is relatively
      constant and present from before birth, calbindin expression is also present
      early but redistributes in the cortex over the first months of life, while
      parvalbumin-immunoreactivity is not observed until between 3 and 6 months of age.
      Investigation of frontal cortical tissue taken post mortem from a series of
      schizophrenic patients and matched control subjects revealed that parvalbumin-,
      but not calretinin-immunoreactive cells are significantly diminished in
      schizophrenia. These observations support the hypothesis that GABAergic deficits
      in schizophrenia may stem from toxic events occurring during cortical development
      which selectively target immature neurons before protection by parvalbumin is
      conferred.

PMID- 11470558
TI  - Aminergic receptors during the development of the human brain: the contribution
      of in vitro imaging techniques.
AB  - The development of the human brain is a complex process and, in this regard, the
      maturation of neurotransmitter systems and their receptors is of special
      interest. The study of these systems requires methodological approaches with
      powerful anatomical resolution. In this paper we review the application of
      visualization procedures to the fine localization, pattern of appearance and
      functional relevance of monoaminergic receptors in postmortem human brain samples
      corresponding to different stages of development (fetal, neonatal, infant). Data
      obtained by using mostly in vitro autoradiography but also in situ hybridization
      and, very recently, second messenger labeling, are discussed, including the
      methodological limitations inherent in working with inmature human tissue. From
      these studies, several conclusions were made. (1) It is possible to visualize, in
      the human brain with high resolution, the presence of neuroreceptors at early
      prenatal stages. (2) The anatomical distribution of monoaminergic receptors in
      the developing human brain is, in general terms, comparable to that found in the
      adult. (3) During the developmental process, some receptors, which are early and
      sometimes transiently expressed, play important thophic roles in the regulation
      of neuronal development: this is the case with the serotonin 5-HT1A receptors,
      which attain peak levels of hyperexpression over the hippocampus (dentate gyrus,
      dendritic areas of CA fields) and the raphe nuclei and show a transient
      expression in the cerebellum, around the 25 week of gestational age. (4)
      Different patterns of ontogenetic appearance for human receptors have been
      identified: dopamine D2-like (caudate, putamen, nigra) and 5-HT1A receptors are
      good examples of prenatal development, while 5-HT1B sites (basal ganglia,
      neocortex) present a mainly postnatal pattern of appearance. (5) Neurotransmitter
      receptors at human fetal stages are already functional from the point of view of
      transducing response.

PMID- 11470559
TI  - Laminar distribution of nicotinic receptor subtypes in cortical regions in
      schizophrenia.
AB  - The laminar cortical distribution of the [125I]alpha-bungarotoxin, [3H]cytisine
      and [3H]epibatidine nicotinic acetylcholine receptor ligands was investigated by
      quantitative autoradiography in autopsy tissue from the cingulate, orbitofrontal
      and temporal cortices of control and schizophrenia subjects matched for age and
      smoking history. Different laminar binding patterns were observed for the various
      nicotinic ligands both in schizophrenic and control brains. [125I]alpha
      Bungarotoxin binding was distributed homogeneously across all cortical layers in
      all three brain regions, with highest binding densities in the cingulate cortex.
      [3H]Cytisine and [3H]epibatidine binding varied across the cortical ribbon, with
      high binding in layers I, III, V and VI, within the three cortical regions. A
      significantly reduced [125I] alpha-bungarotoxin binding (-54%) was observed in
      the cingulate cortex of schizophrenia subjects, in comparison with normal
      individuals who smoked tobacco. In the same brain region also a significantly
      higher [3H]cytisine binding (48-77%) was observed in nearly all layers, except
      for layer I of the schizophrenia subjects, when compared to normal individuals
      with a history of tobacco use. No significant changes in [3H]epibatidine binding
      was observed within the individual cortical layers between control subjects and
      patients with schizophrenia, but when calculated as a whole region (i.e.
      measurements performed across the whole cortical ribbon), the temporal cortex
      showed a significant increase in [3H]epibatidine binding in schizophrenia
      subjects compared to control subjects. The results suggest opposite changes of
      the alpha4beta2 and alpha7 nicotinic receptor subtypes in the cingulate cortex of
      patients with schizophrenia which might reflect involvement of two different
      nicotinic receptor mechanisms in schizophrenia brain.

PMID- 11470560
TI  - D1 and D2 dopamine receptor mRNA expression in whole hemisphere sections of the
      human brain.
AB  - Understanding dopamine signaling in human behavior requires knowledge of the
      distribution of all molecular components involved in dopamine pathways throughout
      the human brain. In the present study, the relative distributions of D1 and D2
      dopamine receptor mRNAs were determined by in situ hybridization histochemistry
      in whole hemisphere sections from normal human post mortem brains. The findings
      confirmed information documented from single structure examination that the
      highest expression of both the D1 and D2 mRNAs were localized to the striatum.
      The cerebral cortex expressed moderate D1 mRNA in all regions with the highest
      signal in the medial orbital frontal area (Brodmann areas 11, 14), the
      paraterminal gyrus (Brodmann area 32) and the insular cortex (Brodmann areas 13
      16), whereas the D2 mRNA expression had very low cortical expression. The bed
      nucleus of the stria terminalis and islands of Calleja had high expression of the
      D1 mRNA and moderate D2 mRNA levels. Moderate to high expression of the D2 mRNA
      was evident in the hippocampal formation, parafascicular and paraventricular
      thalamic nuclei, geniculate bodies, subthalamic nucleus, and pineal gland, all of
      which were devoid of, or showed only faint, D1 mRNA expression. Brainstem
      regions, e.g. substantia nigra, red nucleus, inferior colliculus, medial
      lemniscus, and pontine nuclei expressed D2, but not D1, mRNA. These results
      emphasize the differential anatomical localization of D1 and D2 dopamine receptor
      mRNA neuronal populations in the human brain. The restricted expression of the D1
      mRNA to the cortical mantle and to a few forebrain structures indicates a strong
      involvement of the D1 system in cognitive function.

PMID- 11470561
TI  - Effects of photodynamic therapy on the absorption properties of disulphonated
      aluminum phthalocyanine in tumor-bearing mice.
AB  - Time-resolved reflectance spectroscopy was performed on tumor-bearing mice,
      administered with disulphonated aluminum phthalocyanine (AlS(2)Pc, 5 mg/kg body
      weight), before, during and after photodynamic therapy. This allowed us to
      evaluate the absorption spectrum of AlS(2)Pc in vivo from 610 to 700 nm, and to
      investigate how the therapeutic irradiation affects it. Two tumor locations
      (intraderma on the back and intramuscular in the leg), and two uptake times (3
      and 12 h) were considered. As already observed previously, the absorption
      spectrum of AlS(2)Pc in vivo is centered at 680-685 nm. The irradiation causes a
      blue-shift of the measured line shape, more or less marked depending on the
      experimental conditions. A reduction in absorption is also often observed upon
      illumination with therapeutic light doses.

PMID- 11470562
TI  - 5-Aminolaevulinic acid-mediated photodynamic therapy in multidrug resistant
      leukemia cells.
AB  - To verify if photodynamic therapy (PDT) could overcome multidrug resistance (MDR)
      when it it applied to eradicate minimal residual disease in patients with
      leukemia, we investigated the fluorescence kinetics of 5-aminolaevulinic acid
      (ALA)-induced protoporphyrin IX (PpIX) and the effect of subsequent photodynamic
      therapy on MDR leukemia cells, which express P-glycoprotein (P-gp), as well as on
      their parent cells. Evaluation of PpIX accumulation by flow cytometry showed that
      PpIX accumulated at higher levels in mdr-1 gene-transduced MDR cells (NB4/MDR)
      and at lower levels in doxorubicin-induced MDR cells (NOMO-1/ADR) than in their
      parent cells. A P-gp inhibitor could not increase PpIX accumulation. Measurement
      of extracellular PpIX concentration by fluorescence spectrometry showed that P-gp
      did not mediate the fluorescence kinetics of ALA-induced PpIX production.
      Assessment of ferrochelatase activity using high-performance liquid
      chromatography indicated that PpIX accumulation in drug-induced MDR cells was
      probably regulated by this enzyme. Assessment of phototoxicity of PDT using the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed
      that PDT was effective in NB4, NB4/MDR, NOMO-1 and NOMO-1/ADR cells, which
      accumulated high levels of PpIX, but not effective in K562 and K562/ADR cell
      lines, which accumulated relatively low levels of PpIX. These findings
      demonstrate that P-gp does not mediate the ALA-fluorescence kinetics, and
      multidrug resistant leukemia cells do not have cross-resistance to ALA-PDT.

PMID- 11470563
TI  - Photo-activation of hypericin with low doses of light promotes apparent photo
      resistance in human histiocytic lymphoma U937 cells.
AB  - We have observed that exposure of U937 cells, pre-incubated for 18 h with 0.2
      microM hypericin, to 599 nm laser radiation with a fluence of 2.5 J/cm(2) renders
      them insensitive to higher light doses. In fact, pre-sensitized cells appear to
      be fully resistant to light doses that normally determine massive cellular
      apoptosis in experimental photo-dynamic therapy. The appearance of the photo
      resistance, as measured by evaluating the changes in levels of expression of pro
      and anti apoptotic proteins, PARP fragmentation and cell viability is exclusively
      observed with exposure to light doses not exceeding 5-6 J/cm(2). Above this
      energy, necrosis replaces apoptosis upon photo-stimulation of U937 cells. Here,
      we describe the appearance of photo-resistance in hypericin-loaded U937 cells,
      but could not fully unravel the molecular mechanism underlying this process.
      However, the observed stimulation of the expression of the HSP-70 protein upon
      photo-induced stress may suggest its involvement in this process.

PMID- 11470564
TI  - Effects of pH and acetylation on Hg(2+)-induced purple to blue transition in
      bacteriorhodopsin.
AB  - Effects of Hg(2+) ions on the absorption spectrum of bacteriorhodopsin have been
      measured at different pH values and after acetylation. UV-difference spectroscopy
      and CD spectra show that Hg(2+)-induced color change is essentially similar to
      that caused by removal of cations or acidification. The ability of Hg(2+)-induced
      purple-to-blue transition is pH-dependent and exhibits a maximum at pH 5.5.
      Acetylation influences the absorption in the same way as Hg(2+) ions and
      accelerates Hg(2+)-induced purple to blue transition. All these results strongly
      suggest that the Hg(2+) effect is not a specific binding but just a replacement
      of intrinsic cations on the membrane surface, where they form a double layer. The
      composition of the double layer determines the surface pH on the membrane, which
      affects the color of the bacteriorhodopsin.

PMID- 11470565
TI  - Erythema UV-B exposure near the Antarctic Peninsula and comparison with an
      equatorial site.
AB  - Observations of UV-B radiation in the area of the Antarctic Peninsula are
      described, with the objective to obtain an evaluation of the UV-B enhancements
      observed during ozone hole episodes, and compare these with equatorial values.
      The enhancements observed during Southern Hemisphere spring are described in
      terms of a specific case of enhancement, at the Antarctic peninsula, which has
      shown a maximum UV-B index of 8.7, in October 1998. The average enhancement
      between the autumn-unperturbed and spring-perturbed periods results in an UV-B
      index of 5.4, but with large fluctuations in which much larger indices are
      produced. These values are compared to indices normally observed in the
      equatorial region. For measurements obtained with the same kind of instrument at
      Natal (5.8 degrees S, 35.2 degrees W), the UV-B index varies between 7 and 14,
      which means that enhanced UV-B indices in the Antarctic Peninsula may become of
      the same order of magnitude of the lower limit equatorial values.

PMID- 11470566
TI  - The photosensitizing effect of the photoproduct of protoporphyrin IX.
AB  - The photodynamic effect of a photoproduct of protoporphyrin IX (PpIX) induced by
      5-aminolevulinic acid (ALA) was investigated in WiDr cells, a human
      adenocarcinoma cell line. The fluorescence excitation and emission spectra of
      PpIX and the photoproduct were measured. After 1, 3 or 5 min exposure of the ALA
      incubated cells to 140 mW/cm(2) light at 635 nm, the photoproduct--the chlorin
      photoprotoporphyrin (Ppp), had an emission band around 670 nm. The Ppp excitation
      peak at 670 nm is well separated from the PpIX peak at 635 nm. The outcome of
      photodynamic therapy (PDT) was determined by measuring intracellular fluorescence
      intensity of propidium iodide (PI) 2 h following PDT and methylene blue (MB)
      staining 24 h following PDT. A significant increase in the fluorescence intensity
      of PI was noted when the ALA-loaded cells were exposed to 670 nm light after
      exposure to 635 nm, indicating enhanced cell membrane inactivation induced by the
      photodynamic action of the photoproduct. However, the fraction of the cells that
      survived following the same treatment as measured by MB staining was not
      significantly affected based on an analysis of variance. The fluorescence of PpIX
      decayed significantly during 635 nm light exposure. Exposure to light at 670 nm
      does not lead to any photodegradation of PpIX. The fluorescence of Ppp was
      bleached during 670 nm light exposure. Exposure of Ppp at 670 nm gives no PpIX
      back. Thus, the phototransformation of PpIX to Ppp is probably not a reversible
      process.

PMID- 11470567
TI  - Photophysical properties of lumichromes in water.
AB  - The photophysics of lumichrome, 1-methyllumichrome, and lumiflavin in water
      solutions have been investigated. Fluorescence lifetimes of 2.7 and 2.2 ns were
      observed for lumichrome and 1-methyllumichrome, respectively, the corresponding
      triplet state lifetimes of 17 and 18 micros have been obtained from the transient
      absorption spectra. Evidence for long lived species with absorption maxima near
      450 nm and lifetimes of ca. 400 micros has been found in the transient absorption
      spectra of both lumichromes. Quantum yields for the sensitised production of
      singlet oxygen, phi(Delta), are 0.36 and 0.41 for lumichrome and 1
      methyllumichrome, respectively, in D(2)O.

PMID- 11470568
TI  - Neutral liposome-mediated delivery process of fluorescein-modified
      oligonucleotides in cultured human keratinocytes.
AB  - We propose a model of the intracellular delivery process in which fluorescein
      labeled natural oligonucleotides (F-DNA) are transferred into the nuclei of
      cultured human keratinocytes. By encapsulation in neutral multilamellar lecithin
      liposomes, the F-DNA appeared to be protected against intracellular interactions
      with cellular materials and nuclease attacks in the cytoplasm during the process.
      The intracellular behavior of F-DNA and fluorescent phospholipid-labeled
      liposomes was observed by means of fluorescence analysis. Results showed that: F
      DNA encapsulated in neutral multilamellar liposomes reached the cellular nuclei
      more efficiently than either free F-DNA, or F-DNA in unilamellar liposomes; the
      liposomal membranes appeared to be left in the cytoplasm. The reaction of F-DNA
      with complementary DNA was suggested by a rapid quenching of the fluorescence in
      the nucleus. In addition, the fluorescence decrease was evidently suppressed in
      the cytoplasm, indicating a protective effect of the neutral multilamellar
      liposomes against the interaction of F-DNA with cytoplasmic materials. The
      application of these findings to 'photo'-antisense studies has been discussed,
      where suppression of a gene expression is attempted by using oligonucleotide
      attached fluorescein with the aid of a photo-induced covalent binding property.

PMID- 11470569
TI  - Induction of mycosporine-like amino acids (MAAs) in cyanobacteria by solar
      ultraviolet-B radiation.
AB  - Three filamentous and heterocystous N(2)-fixing cyanobacteria, Anabaena sp.,
      Nostoc commune and Scytonema sp. were tested for the presence of ultraviolet
      absorbing mycosporine-like amino acids (MAAs) and their induction by solar
      ultraviolet-B (UV-B) radiation. High performance liquid chromatographic (HPLC)
      studies revealed the presence of only one type of MAAs in all three
      cyanobacteria, that was identified as shinorine, a bisubstituted MAA containing
      both glycine and serine groups having an absorption maximum at 334 nm and a
      retention time of around 2.8 min. There was a circadian induction in the
      synthesis of MAAs when the cultures were exposed to mid-latitude solar radiation
      (Playa Union, Rawson, Chubut, Patagonia, Argentina) for 3 days, 4-6th February,
      2000. Solar radiation was measured by an ELDONET (European Light Dosimeter
      Network) filter radiometer permanently installed on the roof of the Estacion de
      Fotobiologia Playa Union (43 degrees 18' S; 65 degrees 03' W). The maximum
      irradiances were around 450-500, 45-50 and 1.0-1.2 Wm(-2) for PAR (photosynthetic
      active radiation), UV-A (ultraviolet-A) and UV-B (ultraviolet-B), respectively.
      PAR and UV-A had no significant impact on MAA induction while UV-B induced the
      synthesis of shinorine in all three cyanobacteria. Shinorine was found to be
      induced mostly during the light period. During the dark period the concentration
      stayed almost constant. In addition to shinorine, another unidentified, water
      soluble, brownish compound with an absorption maximum at 315 nm was found to be
      induced by UV-B only in Scytonema sp. and released into the medium. This
      substance was neither found in Anabaena sp. nor in Nostoc commune. Judging from
      the results, the studied cyanobacteria may protect themselves from deleterious
      short wavelength radiation by their ability to synthesize photoprotective
      compounds in response to UV-B radiation.

PMID- 11470570
TI  - Induction of phr gene expression in E. coli strain KY706/pPL-1 by He-Ne laser
      (632.8 nm) irradiation.
AB  - We have observed that He-Ne laser irradiation of E. coli strain KY706/pPL-1 leads
      to induction of photolyase gene, phr. The magnitude of induction was found to
      depend on the He-Ne laser fluence, fluence rate and post-irradiation incubation
      period in the nutrient medium. The optimum values for fluence and fluence rate
      were 7x10(3) J/m(2) and 100 W/m(2), respectively, and the induction of phr gene
      was observed to saturate beyond an incubation period of approximately 2 h.
      Experiments carried out with singlet oxygen quenchers and with D(2)O suggest that
      the effect is mediated via singlet oxygen. Photoreactivation studies carried out
      after UVC exposure of both the He-Ne laser-exposed as well as unexposed cells
      showed a larger surviving fraction in the He-Ne laser pre-irradiated cells. This
      can be attributed to He-Ne laser irradiation-induced induction of phr expression.
      However, since even without photoreactivating light He-Ne laser pre-irradiated
      cells show higher survival against UVC radiation it appears that He-Ne laser
      irradiation induces both light-dependent as well as dark DNA repair processes.

PMID- 11470573
TI  - Neuroprotection in stroke: is it time to consider large-molecule drugs?

PMID- 11470571
TI  - Ecotypic differences in responses of Arabidopsis thaliana L. to elevated
      polychromatic UV-A and UV-B+A radiation in the natural environment: a positive
      correlation between UV-B+A inhibition and growth rate.
AB  - The effects of supplementary ultraviolet-A (UV-A) and ultraviolet-B+A (UV-B+A) in
      the natural environment on the growth and morphology of various ecotypes of
      Arabidopsis thaliana were investigated. The ecotypes investigated were Columbia
      (Col-4), Landsberg erecta (Ler-0), Cvi-0, Wassilewskija, Enkheim-D, Aa-0 and Di
      1. The mutant hy-4 was also used. Results varied with the radiation treatment,
      ecotype and parameter measured. Plants subjected to elevated UV-A were both
      insensitive (all parameters Cvi-0 and Col-4) and sensitive. When responses to UV
      A occurred they were mostly inhibitory (all significant responses of Di-1 and
      Enkheim-D, most parameters of Wassilewskija, and some parameters of hy-4),
      however, promotive affects were observed for some parameters of Aa-0 and Ler-0.
      Supplementary UV-B+A inhibited all parameters of Di-1 and Enkheim-D and most
      parameters of Col-4, Ler-0 and hy-4, but Wassilewskija, Aa-0 and Cvi-0 were
      mostly insensitive. The magnitude of the UV-B+A response varied with ecotype
      (compare Di-1 with Ler-0). Some ecotypes were sensitive to UV-A but not UV-B+A
      (Aa-0), whereas others (Ler-0, Col-4) show the opposite sensitivities. A linear
      relationship is reported between the degree of UV-B+A inhibition of each ecotype
      and growth rate. The higher the growth rate the more susceptible the ecotype is
      to UV-B+A inhibition. This relationship holds for the majority of growth
      parameters measured.

PMID- 11470574
TI  - Cancer drug delivery is hot stuff.

PMID- 11470576
TI  - Electrifying new treatment for epilepsy.

PMID- 11470575
TI  - Drug-free tolerance of transplanted tissue.

PMID- 11470579
TI  - Personalia.

PMID- 11470581
TI  - Gene therapy versus protein-based therapy: a matter of pharmacokinetics.

PMID- 11470580
TI  - Animal models and human genome diversity: the pitfalls of inbred mice.

PMID- 11470582
TI  - Transgenic gene knockouts: a functional platform for the industry.

PMID- 11470583
TI  - Novel proteases for drug discovery.

PMID- 11470584
TI  - Proteomics: delivering new routes to drug discovery - Part 1.

PMID- 11470585
TI  - EuroBiochips: spot the difference!

PMID- 11470586
TI  - The application of non-combinatorial chemistry to lead discovery.
AB  - Non-combinatorial chemistry is a powerful technology for the synthesis of large
      numbers of compounds, with complete control over the properties of those
      compounds. We have developed a Library Creation, Registration and Automation
      system (LiCRA), which harnesses an efficient non-combinatorial chemistry design
      and synthesis engine, together with high-throughput automated purification. This
      LiCRA system also operates in a closed loop mode for hit-to-lead optimization,
      and contains an integrated IT system that controls and facilitates all aspects of
      the operation from design to registration. Quality has been our watchword, from
      the quality of compound design through to the quality of the products.

PMID- 11470587
TI  - Targeting the molecular mechanism of DNA replication.
AB  - Genome stability is crucial for the complete maintenance of the cellular pathways
      that govern the cell cycle. As a result of irregularities in DNA replication
      occurring throughout the S phase, key genes that regulate cell cycle pathways are
      damaged, giving rise to single-base mutations and chromosomal aberrations. Thus,
      the efficient replication of the genome, which depends on a precise temporal and
      spatial pattern of activation of origins of replication, is greatly impaired. The
      approach discussed below aims at monitoring the replication pattern and the
      kinetics of replication throughout the entire genome of living cells. It could
      shed light on the mechanisms by which drugs act on DNA replication and, moreover,
      it might assist the discovery and design of novel drugs that inhibit cell
      proliferation under pathophysiological conditions.

PMID- 11470588
TI  - Receptor-mediated gene transfer by phage-display vectors: applications in
      functional genomics and gene therapy.
AB  - Recent studies have demonstrated targeted gene-delivery to mammalian cells using
      modified phage-display vectors. Specificity is determined by the choice of the
      genetically displayed targeting ligand. Without targeting, phage particles have
      virtually no tropism for mammalian cells. Thus, novel ligands can be selected
      from phage libraries by their ability to deliver a reporter gene to targeted
      cells. Together with advances in cDNA display technologies, these findings offer
      new opportunities for the use of phage-display technology in functional genomics.
      In addition, targeted phage particles have potential as alternative gene therapy
      vectors that can be further improved using directed evolution.

PMID- 11470589
TI  - Modelling and simulation in clinical drug development.
AB  - Pharmaceutical companies are under greater pressure than ever before to improve
      the R&D process (1). There is a growing need to increase productivity in R&D, and
      to use technologies that can both increase and more efficiently facilitate the
      flow of products through the development pipeline. This article describes how the
      twin processes of modelling and simulation are being used to improve the
      efficiency of the clinical drug-development process, and consequently how these
      methodologies have delivered significant benefits in the drive to save time,
      money (and additionally assisted in ensuring an 'optimal quality' drug label) in
      the development of novel therapeutic agents.

PMID- 11470590
TI  - Monitor: molecules and profiles.
AB  - Monitor provides an insight into the latest developments in drug discovery
      through brief synopses of recent presentations and publications together with
      expert commentaries on the latest technologies. There are two sections: Molecules
      summarizes the chemistry and the pharmacological significance and biological
      relevance of new molecules reported in the literature and on the conference
      scene; Profiles offers commentary on promising lines of research, emerging
      molecular targets, novel technology, advances in synthetic and separation
      techniques and legislative issues.

PMID- 11470591
TI  - Drug delivery.

PMID- 11470592
TI  - Combinatorial chemistry.

PMID- 11470594
TI  - Next generation therapeutics. Web alert.

PMID- 11470596
TI  - From symptomatic treatments to causative therapy?
AB  - The search for genes that predispose individuals to develop common chronic
      diseases such as asthma, diabetes and Alzheimer's promises to give insights into
      their molecular pathogenesis. This will lead to the development of therapies that
      modulate the pathology, rather than the physiology of these diseases. As academia
      and the pharmaceutical industry increasingly focus on this challenge, the genetic
      dissection of Alzheimer's is spearheading attempts to shift the therapeutic
      paradigm away from symptomatic to curative treatments.

PMID- 11470597
TI  - Chemical genetic approaches for the elucidation of signaling pathways.
AB  - New chemical methods that use small molecules to perturb cellular function in
      ways analogous to genetics have recently been developed. These approaches include
      both synthetic methods for discovering small molecules capable of acting like
      genetic mutations, and techniques that combine the advantages of genetics and
      chemistry to optimize the potency and specificity of small-molecule inhibitors.
      Both approaches have been used to study protein function in vivo and have
      provided insights into complex signaling cascades.

PMID- 11470598
TI  - Human antibodies as next generation therapeutics.
AB  - Antibodies and antibody derivatives constitute twenty five percent of
      therapeutics currently in development, and a number of therapeutic monoclonal
      antibodies have recently reached the market. All antibodies approved by the US
      Food and Drug Administration, however, contain mouse protein sequences. These
      partially murine antibodies, therefore, have the potential to elicit allergic or
      other complications when used in human patients. Recent developments aim to
      reduce or eliminate murine components, and fully human antibodies are rapidly
      becoming the norm. A number of technologies exist which enable the development of
      100% human antibodies.

PMID- 11470599
TI  - High-throughput docking for lead generation.
AB  - Recent improvements in flexible docking technology may lead to a bigger role for
      computational methods in lead discovery. Although fast and accurate computational
      prediction of binding affinities for an arbitrary molecule is still beyond the
      limits of current methods, the docking and screening procedures can select small
      sets of likely lead candidates from large libraries of either commercially or
      synthetically available compounds.

PMID- 11470600
TI  - The computational prediction of toxicity.
AB  - Recent developments in the prediction of toxicity from chemical structure have
      been reviewed. Attention has been drawn to some of the problems that can be
      encountered in the area of predictive toxicology, including the need for a multi
      disciplinary approach and the need to address mechanisms of action. Progress has
      been hampered by the sparseness of good quality toxicological data. Perhaps too
      much effort has been devoted to exploring new statistical methods rather than to
      the creation of data sets for hitherto uninvestigated toxicological endpoints
      and/or classes of chemicals.

PMID- 11470601
TI  - Visual and computational analysis of structure--activity relationships in high
      throughput screening data.
AB  - Novel analytic methods are required to assimilate the large volumes of structural
      and bioassay data generated by combinatorial chemistry and high-throughput
      screening programmes in the pharmaceutical and agrochemical industries. Recent
      work in visualisation and data mining has been used to develop structure-
      activity relationships from such chemical-biological datasets.

PMID- 11470602
TI  - Screening of drug candidates for their drug--drug interaction potential.
AB  - Within the past year, additional papers have been published that focus on higher
      throughput drug-interaction screening. Some papers have described enzyme assays
      that can be used to evaluate inhibition or induction of the human cytochrome
      P450s. At the same time, numerous investigators have developed computational (in
      silico) methods to predict interactions and have validated the approach using in
      vitro (assay-derived) data. These so called 'in silico--in vitro' correlations
      have great potential and may complement existing 'in vitro--in vivo'
      correlations.

PMID- 11470603
TI  - Structural genomics: opportunities and challenges.
AB  - Following the complete genome sequencing of an increasing number of organisms,
      structural biology is engaging in a systematic approach of high-throughput
      structure determination called structural genomics to create a complete inventory
      of protein folds/structures that will help predict functions for all proteins.
      First results show that structural genomics will be highly effective in finding
      functional annotations for proteins of unknown function.

PMID- 11470604
TI  - SH2 domain inhibition: a problem solved?
AB  - The past two years have witnessed a number of significant advances in the design
      of SH2 inhibitors of both Src and Grb2. For Src, several non-peptide templates
      have been developed with high affinity, and one case, in the context of bone
      binding phosphotyrosine bioisostere, has yielded an in vivo active antiresorptive
      agent. Similarly, high-affinity Grb2 SH2 inhibitors with novel phosphotyrosine
      replacements have now been reported that demonstrate, for the first time,
      cellular activities consistent with an anticancer agent.

PMID- 11470605
TI  - Protein tyrosine phosphatases: prospects for therapeutics.
AB  - Protein tyrosine phosphatases (PTPs) form a large family of enzymes that serve as
      key regulatory components in signal transduction pathways. Recent gene knockout
      studies in mice identify PTP1B as a promising target for anti-diabetes/obesity
      drug discovery. PTPs are also implicated in a wide variety of other disorders,
      including cancer. Significant progress has been made in identifying small
      molecules that simultaneously bind both the active site and a unique adjacent
      site that enables specific inhibition of individual PTP isoenzymes. As a
      consequence, there are compelling reasons to believe that PTP inhibitors may
      ultimately serve as powerful therapeutic weapons in our arsenal for battling
      human diseases.

PMID- 11470606
TI  - Microtubule-stabilizing agents: a growing class of important anticancer drugs.
AB  - Microtubule-stabilizing agents continue to play an important role in anticancer
      drug discovery and development. New agents were again discovered in the past
      year, including small synthetic molecules. At least three new taxanes and two
      compounds of the epothilone class of natural products underwent clinical trials
      in 2000. Unexpected new findings about synergistic effects between different
      microtubule-stabilizing agents in vitro raise new prospects for combination
      chemotherapy.

PMID- 11470607
TI  - The next generation of PDE4 inhibitors.
AB  - A number of highly potent PDE4 inhibitors are being developed for the treatment
      of asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, multiple
      sclerosis and Crohn's disease. Cilomilast (Ariflo, SB 207499, SmithKline
      Beecham), the most advanced member of the class in Phase III clinical trials, was
      reported to have a limited therapeutic window. Other inhibitors with improved
      profiles in preclinical models are entering into (or are in) clinical trials. The
      recent developments in understanding PDE4 catalysis, inhibitor binding and their
      emetic response should facilitate the design of the next generation of PDE4
      inhibitors.

PMID- 11470608
TI  - Drug delivery: an odyssey of 100 years.
AB  - Drug delivery has metamorphosed from the concept of a pill to molecular medicine
      in the past 100 years. Better appreciation and integration of pharmacokinetic and
      pharmacodynamic principles in design of drug delivery systems has led to improved
      therapeutic efficacy. A greater understanding of the molecular transport in
      relation to physico-chemical properties has led to the evolution of a
      biopharmaceutics classification system, which should be a future road map,
      governing drug design, development and delivery. While drugs belonging to class I
      and II will be delivered by established platform technologies, novel delivery
      strategies will evolve and mature to realize the potential of 'new generation'
      biotech and non biotech drugs belonging to class III and IV, respectively.

PMID- 11470609
TI  - Polymers in drug delivery.
AB  - Advances in polymer science have led to the development of several novel drug
      delivery systems. A proper consideration of surface and bulk properties can aid
      in the designing of polymers for various drug-delivery applications.
      Biodegradable polymers find widespread use in drug delivery as they can be
      degraded to non-toxic monomers inside the body. Novel supramolecular structures
      based on polyethylene oxide copolymers and dendrimers are being intensively
      researched for delivery of genes and macromolecules. Hydrogels that can respond
      to a variety of physical, chemical and biological stimuli hold enormous potential
      for design of closed-loop drug-delivery systems. Design and synthesis of novel
      combinations of polymers will expand the scope of new drug-delivery systems in
      the future.

PMID- 11470610
TI  - Prediction of pharmacokinetic properties using experimental approaches during
      early drug discovery.
AB  - There has been a significant increase in the number of compounds synthesized in
      early drug-discovery programs with the advances in combinatorial chemistry and
      high-throughput biological screening efforts. Various in silico, in vitro and in
      situ approaches have been described in literature that achieve higher throughput
      pharmacokinetic screening. In silico methodologies have mainly attempted to
      quantify the prospects of oral absorption of compounds based upon their physico
      chemical properties. There is a greater availability of in vitro and in situ
      approaches to screen compounds for intestinal permeability (as a surrogate for
      absorption) and metabolic stability (as a surrogate for clearance). More recent
      modifications of the in vitro and in situ approaches to assess the potential of
      absorption and metabolism have enabled a higher throughput and an ability to
      correlate better with in vivo pharmacokinetics of compounds.

PMID- 11470611
TI  - Chemogenomic approaches to drug discovery.

PMID- 11470613
TI  - Data mining approach to policy analysis in a health insurance domain.
AB  - This study examined the characteristics of the knowledge discovery and data
      mining algorithms to demonstrate how they can be used to predict health outcomes
      and provide policy information for hypertension management using the Korea
      Medical Insurance Corporation database. Specifically, this study validated the
      predictive power of data mining algorithms by comparing the performance of
      logistic regression and two decision tree algorithms, CHIAD (Chi-squared
      Automatic Interaction Detection) and C5.0 (a variant of C4.5) using the test set
      of 4588 beneficiaries and the training set of 13,689 beneficiaries. Contrary to
      the previous study, the CHIAD algorithm performed better than the logistic
      regression in predicting hypertension, and C5.0 had the lowest predictive power.
      In addition, the CHIAD algorithm and the association rule also provided the
      segment-specific information for the risk factors and target group that may be
      used in a policy analysis for hypertension management.

PMID- 11470614
TI  - Medical informatics--the state of the art in the Hospital Authority.
AB  - Since its inception in 1990, the Hospital Authority (HA) has strongly supported
      the development and implementation of information systems both to improve the
      delivery of care and to make better information available to managers. This paper
      summarizes the progress to date and discusses current and future developments.
      Following the first two phases of the HA information technology strategy the
      basic infrastructural elements were laid in place. These included the foundation
      administrative and financial systems and databases; establishment of a wide area
      network linking all hospitals and clinics together; laboratory, radiology and
      pharmacy systems with access to results in the ward. A major push into clinical
      systems began in 1994 with the clinical management system (CMS), which
      established a clinical workstation for use in both ward and ambulatory settings.
      The CMS is now running at all major hospitals, and provides single logon access
      to almost all the electronically collected clinical data in the HA. The next
      phase of development is focussed on further support for clinical activities in
      the CMS. Key elements include the longitudinal electronic patient record (ePR),
      clinical order entry, generic support for clinical reports, broadening the scope
      to include allied health and the rehabilitative phase, clinical decision support,
      an improved clinical documentation framework, sharing of clinical information
      with other health care providers and a comprehensive data repository for analysis
      and reporting purposes.

PMID- 11470615
TI  - Knowledge representation and retrieval using conceptual graphs and free text
      document self-organisation techniques.
AB  - Hospitals generate and store a large amount of clinical data each year, a
      significant portion of which is in free text format. Conventional database
      storage and retrieval algorithms are incapable of effectively processing free
      text medical data. The rich information and knowledge buried in healthcare
      records are unavailable for clinical decision-making. We examined a number of
      techniques for structuring and processing free text documents to effective and
      efficient for information retrieval and knowledge discovery. One critical success
      criterion is that the complexity of the techniques must be polynomial both in
      space and time for them to be able to cope with very large databases. We used
      conceptual graphs (CG) to capture the structure and semantic
      information/knowledge contained within the free text medical documents. Ordering
      and self-organising techniques (lattice techniques and knowledge space) were used
      to improve organisation of concepts from standard medical nomenclatures and large
      sets of free text medical documents. Pair-wise union of CG was performed to
      identify the common generalisation structure and a lattice structure of these CG
      documents. A combination of all three techniques allowed us to organise a set of
      9000 discharge summaries into a generalisation hierarchy that supported efficient
      and rich information/knowledge retrieval.

PMID- 11470616
TI  - Development and deployment of a web-based physician order entry system.
AB  - The computer-based Physician Order Entry System (POES) has been employed in many
      clinical institutes in Taiwan. Most of the POES systems are developed in the two
      tier client-server architecture, and a large portion of the systems are
      constructed on a mainframe or even a single PC. The exponential growth of the
      Internet has had a tremendous impact on our society in recent years. In
      consideration of the future user interface and system architecture, we have
      developed a three-tier web-based Physician Order Entry System and successfully
      deployed it in the Wang-Fang Hospital in Taipei. The system is the first POES
      based on three-tier and World Wide Web (WWW) in Taiwan. The system provides the
      Subjective, Objective, Assessment, and Plan (SOAP) structure for the physician to
      enter subject, object, diagnoses, medicine dosage, treatment and laboratory test
      request, and prints out the prescription and necessary document. The doctor can
      also retrieve the patient's medical record on the system. One of the special
      characteristics of the system is its personalized design. The doctor can define
      their own diagnosis, medicine and treatment database and any combination of these
      to facilitate their clinical work. The system has been reviewed since February
      1999. The result shows that the clinical procedure has become more efficient, and
      the chances of omission have been reduced. The system is very stable and the Open
      Database Connectivity (ODBC) database access did not show any delay in the
      network. Since we have incorporated many new web-programming techniques, the
      progress of the techniques will improve the system performance in the future.

PMID- 11470617
TI  - Computerization of clinical practice in Hong Kong.
AB  - The objective of this study was to assess the current level of computerization in
      clinical practice in Hong Kong through a population-based, physician survey
      conducted in 2000.A self-completed, 20-question, postal questionnaire was sent to
      4850 randomly selected doctors in Hong Kong. We received 897 completed responses.
      Over one-third of doctors in the overall sample were already recording patient
      summaries, processing laboratory results and specialist reports, and preparing
      referral notes electronically. Patient registration (52.2%), billing systems
      (40.2%), appointment scheduling (39.9%), and payroll (36.9%), were the commonest
      administrative functions to have been computerized. Seventy per cent of doctors
      in solo or small-group ('individual') practices did not yet have any clinical
      function computerized compared with only 30.7% for those working in large,
      corporate organizations. Similarly, approximately two-thirds of administrative
      tasks in 'individual' clinics were not computerized, while corporate physicians
      reported a corresponding percentage of 39.3%. Younger age, male gender,
      specialist qualifications, more computers in the practice, higher numbers of
      administrative tasks already computerized, higher levels of knowledge about and
      positive attitudes towards computer applications in clinical practice were all
      positively associated with more clinical tasks already computerized in the
      practice. The present study has systematically documented the extent of clinical
      computer use in Hong Kong and identified areas for improvement as well as
      specific groups of physicians who might benefit from targeted efforts promoting
      computerization in practice.

PMID- 11470618
TI  - The retrieval effectiveness of medical information on the web.
AB  - The World Wide Web has become such an extensive health information repository in
      the world that it is increasingly difficult to search for relevant medical
      information. Many search tools have been developed to help users look for
      relevant health information on the web, but most of them are still not efficient.
      In this paper, we discuss some available on-line solutions to medical information
      retrieval and compare the performances of some general and medicine-specific
      search engines with the MediAgent, which has been developed by the National
      University of Singapore (NUS) Medical Informatics Programme. Although a number of
      medicine-specific searching techniques have been developed, the difficulty of
      finding medical information still remains because medical search engines are
      generally not as effective as generic search engines. Different from other search
      tools, MediAgent's efficiency was quite high, taking only an average of 1.5 links
      to retrieve the answers, but its retrieving effectiveness is not good enough due
      to the short period of operation. Whilst the MediAgent project cannot claim to
      have all the solutions, it nevertheless offers a new alternative to system
      implementation. New techniques need to be explored in order to overcome the
      issues of medical information retrieval on the Internet.

PMID- 11470619
TI  - Fuzzy logic and its applications in medicine.
AB  - Fuzzy set theory and fuzzy logic are a highly suitable and applicable basis for
      developing knowledge-based systems in medicine for tasks such as the
      interpretation of sets of medical findings, syndrome differentiation in Eastern
      medicine, diagnosis of diseases in Western medicine, mixed diagnosis of
      integrated Western and Eastern medicine, the optimal selection of medical
      treatments integrating Western and Eastern medicine, and for real-time monitoring
      of patient data. This was verified by trials with the following systems that were
      developed by our group in Vietnam: a fuzzy Expert System for Syndromes
      Differentiation in Oriental Traditional Medicine, an Expert System for Lung
      Diseases using fuzzy logic, Case Based Reasoning for Medical Diagnosis using
      fuzzy set theory, a diagnostic system combining disease diagnosis of Western
      Medicine with syndrome differentiation of Oriental Traditional Medicine, a fuzzy
      system for classification of Western and Eastern medicaments and finally, a fuzzy
      system for diagnosis and treatment of integrated Western and Eastern Medicine.

PMID- 11470620
TI  - The comparative impact of video-consultation on neurosurgical health services.
AB  - This study evaluated the impact of telemedicine technology on the provision of
      neurosurgical health services. We focused on the differences between the use of
      real time audio-visual teleconferencing and teleradiology versus conventional
      telephone consultations in the referral of neurosurgical patients from a large
      district general hospital. All patients requiring emergency neurosurgical
      consultation were included for randomization into telephone consultation only
      (Mode A), teleradiology and telephone consultation (Mode B) and video
      consultation (Mode C). Measures of effectiveness included diagnostic accuracy and
      adverse events during the transfer and Glasgow Outcome Score. In a 10-month
      period, 327 patients were recruited and randomized into the study: the
      male/female ratio was 2:1 and the number of patients required to be transferred
      to the neurosurgical unit was 125 (38%). There was a trend towards a more
      favourable outcome in the video-consultation mode (44%, Mode C), versus
      teleradiology (31%, Mode B), versus telephone consultation (38%, Mode A). The
      interim data of this prospective randomized trial suggests that video
      consultation may have a favourable impact on emergency neurosurgical
      consultations.

PMID- 11470621
TI  - Clinical websites are currently dangerous to health.
AB  - The Internet is becoming a ubiquitous medium, open to all. The paper explores the
      reasons why current health-related websites require extensive review and
      investment to ensure that they address the full spectrum of the audiences who may
      access their site. The audiences are no longer purely local or even solely those
      who work in the health domain. They will include everyone, from professional
      healthcare practitioners to members of the general public. The site web masters
      should also consider the range of purposes for which these disparate groups
      access the site. The language, content intensity and presentation should have a
      different style and be identified by its intended audience to avoid a range of
      problems including mis-interpretation, mis-targetting of content, mis
      representation of source and quality. Inappropriate content and presentation
      could jeopardise the credibility of health sites, and thus healthcare provision,
      with the newly emerging audiences. Recent studies involving the evaluation of
      many web sites have assessed their 'fitness for purpose' as information
      repositories for different audiences. The criteria by which clinically related
      web contents are judged will vary, depending on the type of visitor to the site.
      Formal qualification of web content is ongoing--addressing both structured
      definition [1] and quality criteria [2]. Originators of web material should
      consider the full spectrum of the audiences who may access their site, from
      professional healthcare practitioners to members of the general public, and the
      purposes for which they access the site. The language, content intensity and
      presentation should have a different style and be identified by its intended
      audience to avoid a range of problems including mis-interpretation, mis
      targetting of content, mis-representation of source and quality.

PMID- 11470622
TI  - An evaluation of the use of hand-held computers for bedside nursing care.
AB  - Both keyboard-based and pen-based devices for data input have advantages and
      disadvantages. The suitability of the two input devices for entering different
      types of clinical data into computers remains unclear. This study aimed to
      determine the usefulness of different types of technology for nurses' data entry
      by comparing the utility and efficiency of keyboard and pen-based data input for
      clinical tasks. The study was conducted in the six largest specialties of an
      acute care hospital. In each specialty, several wards were randomly selected, and
      all nurses working in these wards were invited to participate. The input
      prototype was designed according to the type of text that was to be entered into
      the system. Task 1 mainly consisted of structured data, Task 2 contained equal
      amount of structured and textual data, and Task 3 was mainly in textual form.
      Each nurse was asked to complete the three simulations of nursing records (Tasks
      1, 2 and 3). Preliminary findings showed that nurses found the pen-based
      interface easier to use than the keyboard for completing Tasks 1 and 2, but not
      Task 3. In terms of accuracy, the nurses preferred the keyboard to the pen when
      the data were more structured. The pen-based device is not a panacea for all
      kinds of user interface, and more importantly, the choice of input device should
      depend on the amount of structured and textual data.

PMID- 11470623
TI  - Development of a new enzyme-linked immunosorbent assay for the detection of anti
      M2 in primary biliary cirrhosis.
AB  - We developed a new enzyme-linked immunosorbent assay (ELISA) for the detection of
      antimitochondrial antibody (AMA)-M2 in sera from patients with primary biliary
      cirrhosis (PBC), using 2-oxo-acid dehydrogenase complex (2-OADC) purified from
      porcine myocardium as the antigen source. The immunoreactivity was tested in a
      total of 354 sera, including 63 sera from patients with PBC by our ELISA. In the
      sera, indirect immunofluorescence for AMA, former ELISA for anti-pyruvate
      dehydrogenase complex (PDC) and immunoblot assay were performed, respectively. Of
      the 63 sera from patients with PBC, 51 sera (81.0%) were positive for anti-M2 in
      the new ELISA. Thirty-eight of the 63 sera (60.3%) were positive for anti-PDC in
      the former ELISA; the difference was significant between them (P=0.011). None of
      the 291 control sera from healthy volunteers showed reactivity against 2-OADC in
      the new ELISA. Moreover, in comparison with the results of immunoblot analysis,
      sensitivity and specificity in our ELISA to the sera from patients with PBC were
      100 and 92.3%, respectively. Our results indicate that the new ELISA for anti-M2
      using 2-OADC is simple, rapid and sensitive enough for the detection of AMA
      specific to PBC.

PMID- 11470624
TI  - An undescribed subset of neonatal intrahepatic cholestasis associated with
      multiple hyperaminoacidemia.
AB  - Five patients of cholestatic jaundice and multiple hyperaminoacidemias were
      uncovered during neonatal mass screening for homocystinuria. All five patients
      had increased plasma levels of methionine, citrulline, tyrosine, threonine,
      phenylalanine, lysine and arginine. Compared with those of age-matched
      cholestatic disease controls, idiopathic neonatal hepatitis (n=9) and biliary
      atresia (n=14), plasma levels of three amino acids, citrulline, methionine, and
      threonine, were significantly greater, respectively (P<0.01). Liver biopsies
      examined in four patients uniformly showed diffuse hepatic fatty liver with micro
      and macrovesicular droplets without giant cell transformation. Administration of
      fat-soluble vitamins and formula milk containing middle-chain triglyceride
      resulted in normalization of amino acid profiles by 6 weeks after the treatment.
      All liver function tests normalized by 17 months of age.

PMID- 11470625
TI  - Comparison of the dot immunobinding assay and two enzyme-linked immunosorbent
      assay kits for the diagnosis of liver cystic echinococcosis.
AB  - The dot immunobinding assay for the detection of hydatid antigen-specific
      antibodies (HA-DIA) was evaluated in patients with liver cystic and alveolar
      echinococcosis in comparison to two commercial ELISA kits. In 30 patients, E.
      granulosus infection (CE) was confirmed by histopathology or by the presence of
      parasite protoscoleces and/or hooks or specific antigen 5 (Ag5) in cyst fluid
      samples obtained by the fine needle aspiration biopsy (FNAB). Infection of E.
      multilocularis (AE) was diagnosed in two patients by the detection of specific
      anti-Em2(plus) ELISA and -Em18 Western blot antibodies and finally confirmed by
      histopathology. The HA-DIA using bovine hydatid antigens showed a high
      sensitivity in serum samples from CE patients; specific antibodies were found in
      29 of 30 CE patients (96.7%). One negative result has been observed in a patient
      2.6 years after radical surgery with a subsequent albendazole chemotherapy. The
      Echinococcosis ELISA(R) (Dialab Diagnostic) was positive in 23 CE cases (76.7%).
      The correlation between the HA-DIA and the Echinococcosis ELISA(R) was
      statistically significant. By contrast, Echinococcus granulosus IgG ELISA(R)
      (Bordier Affinity Products) gave positive results in only 12 of 30 CE patients
      (40.0%). Sera from two AE patients were high positive in all three methods
      analysed in our study. In non-endemic areas, due to the between-strains
      variations and differences in cyst immunogenic activity, related to the natural
      history of the parasite, a choice of an optimal method for a diagnosis of liver
      cystic echinococcosis has been discussed.The high diagnostic sensitivity and a
      faster one-step procedure, in comparison to traditional enzyme immunoassays, make
      the HA-DIA a very useful method for the diagnosis of CE in non-endemic areas,
      especially in a case of small or degenerating lesions and sterile echinococcal
      cysts with a low immunogenicity. The positive serology for CE frequently requires
      additional differentiation with E. multilocularis-specific antibodies.

PMID- 11470626
TI  - Overexpression of cyclin E and cyclin-dependent kinase 2 is correlated with
      development of hepatocellular carcinomas.
AB  - Mammalian cell cycle progression is regulated by the combined action of
      cyclins/cyclin-dependent kinases (CDKs) and CDK inhibitors. Abnormal expression
      as well as interaction of these proteins may result in malignant transformation
      of cells. To further address the role of these cell cycle proteins in
      hepatocellular carcinomas, we analyzed the expression of cyclin E and CDK2. A
      panel of livers with human hepatocellular carcinoma, liver cirrhosis, and chronic
      hepatitis were used as a human experimental system. The inbred LEC (Long-Evans
      with a cinnamon-like coat color) rats were used as an animal experimental HCC
      model. Immunohistochemical staining of serial paraffin sections was performed
      using antibodies to cyclin E and CDK2. The results showed that cyclin E and CDK2
      were concurrently overexpressed in hepatocellular carcinomas both in human and
      rat livers. Western blot analysis and CDK2 kinase assay demonstrated expression
      levels of cyclin E and CDK2 and CDK2 kinase activity, respectively, and both were
      shown to increase along with the development of hepatocellular carcinomas.
      Analysis of the correlation between expression of cyclin E and CDK2 and
      clinicopathological parameters revealed a significant correlation between
      expression of cyclin E and tumor grade (P=0.013), and PCNA index (P=0.006) as
      well as CDK2 expression (P=0.015). Overexpression of CDK2 tended to be associated
      with poorly differentiated HCCs. The results suggest that overexpression of
      cyclin E and CDK2 plays an important role in the development of hepatocellular
      carcinoma.

PMID- 11470627
TI  - Clinical investigation of endothelin-1 and nitric oxide in patients with portal
      hypertension focusing on plasma levels and immunohistological staining of liver
      tissues.
AB  - Plasma concentrations of endothelin-1 (ET-1) and nitrite/nitrate of patients with
      portal hypertension were measured. Sixteen patients with liver cirrhosis (the LC
      group) and 14 patients with idiopathic portal hypertension (the IPH group) and 12
      healthy subjects (normal controls) were included in this study. The peripheral
      venous plasma concentration of ET-1 was significantly higher in the LC group
      (6.69+/-2.44 pg/ml) than in the IPH group (3.07+/-0.84 pg/ml) and normal controls
      (1.79+/-0.36 pg/ml), while the value in the IPH group was also significantly
      higher than that in normal controls. The peripheral venous plasma concentration
      of nitrite/nitrate was significantly higher in the LC group (67.7+/-38.9
      &mgr;Mol/l) than in the IPH group (32.3+/-24.4 &mgr;Mol/l) and normal controls
      (26.1+/-9.8 &mgr;Mol/l). Hepatic venous plasma concentrations of ET-1 and
      nitrite/nitrate were measured in 8 patients from the LC group and 10 patients
      from the IPH group. The plasma concentration of ET-1 in the hepatic vein was
      significantly higher than that in the peripheral vein in both the LC and the IPH
      groups. The plasma concentration of nitrite/nitrate in the hepatic vein was
      significantly higher than that in the peripheral vein in the LC group. We also
      investigated the localization of ET-1, endothelin receptor (ET receptor) and
      nitric oxide synthase (NOS) in the liver tissue of LC patients (n=10), IPH
      patients (n=10) and normal controls (n=10). The expressions of ET-1, ET A
      receptors, ET B receptors, and inducive NOS (iNOS) were detected in patients with
      LC, and the labeling index (LI) was significantly higher than that in patients
      with IPH and normal controls. The expressions of ET-1, ET A receptors, and ET B
      receptors were found in patients with IPH, and the LI was significantly higher
      than that in normal controls. The expression of endothelial NOS (eNOS) was scarce
      in both LC and IPH patients. From these results, overproduction of ET-1 in the
      liver was regarded as one of the causes of the high plasma concentration of ET-1
      in patients with LC and IPH. One of the causes of the high plasma concentration
      of nitrite/nitrate in LC was considered to be overproduction of nitric oxide (NO)
      in the liver. And we suggested that ET-1 is at a relatively higher density than
      NO in the hepatic sinusoid in LC and IPH.

PMID- 11470628
TI  - Randomized controlled clinical trial of lymphoblastoid interferon-alpha for
      chronic hepatitis C.
AB  - Objective: Most of chronic hepatitis C patients with HCV-genotype 1 and a high
      virus load fail to eradicate the HCV-RNA by the interferon (IFN) or IFN/ribavirin
      therapy. But in these patients, IFN is often effective with regard to
      normalization of alanine aminotransferase (ALT). We had therefore the following
      two randomized controlled clinical trials to evaluate the effect of IFN which
      reduce ALT and maintain normalization of ALT. One approach (study 1) was to
      compare the efficacy of a 6 month course of three different dosages of
      recombinant IFN-alpha-2a in patients with chronic hepatitis C associated with HCV
      genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml. Another
      approach (study 2) was to make clear the significance of an additional 6 month
      course of IFN in patients who had biochemical response during the first 6 month
      course of IFN (study 1). Methods: (1) Study 1; 45 patients with HCV-genotype 1b
      and a high serum HCV-RNA level of more than 1 Meq/ml were randomly assigned into
      three equal groups; group 1 was treated with 3 million units (MU), group 2 with 6
      MU and group 3 with 9 MU. They were treated with IFN 3 times weekly for 6 months.
      Biochemical response was defined as normalization of ALT at the 6 month after
      initiation of IFN; (2) Study 2; Subsequently, of 23 patients with biochemical
      response by the first study, 22 were randomly assigned to two groups; patients in
      group A were continued to receive 3 MU of IFN-alpha-2a three times a week for an
      additional 6 months and patients in group B were discontinued IFN therapy.
      Results: (1) Study 1; One patient in group 1, three in group 2 and five in group
      3 withdrew from IFN therapy because of IFN-related side-effects. Biochemical
      response was 10 (66.7%) patients of group 1,8 (53.3%) of group 2 and 5 (33%) of
      group 3 by the intention-to-treat (ITT) analysis. The biochemical response rate
      in group 1 was slightly higher than that in other two groups by the Cochran
      Armitage two-tailed test (P=0.066). With respect to serum HCV-RNA level, one
      patient in group 1, six patients in group 2 and four patients in group 3 became
      negative for HCV-RNA by reversed transcription nested-polymerase chain reaction
      (RT nested-PCR) at the end point of first 6 month course of IFN; (2) Study 2; The
      maintenance rate of ALT normalization was 88.9% (9/11) in group A and 11.1%
      (2/11) in group B. The maintenance rate of ALT normalization in group A was
      significantly higher than that in group B by the Fisher exact's test (P=0.0089).
      With respect to serum HCV-RNA level by RT nested-PCR, four patients in group A
      had negative HCV-RNA at the end of an additional IFN therapy. On the other hand,
      all the patients in group B had positive HCV-RNA at the same time. Conclusion:
      Our data suggested that a prolonged IFN therapy using a dose of 3 MU of IFN-alpha
      2a is safe strategy to reduce ALT and to maintain ALT normalization in patients
      with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml.

PMID- 11470629
TI  - Comparison of clinical laboratory liver tests between asymptomatic HBV and HCV
      carriers with persistently normal aminotransferase serum levels.
AB  - We examined the clinicopathological state in asymptomatic hepatitis C virus (HCV)
      carriers with persistently normal aminotransferase serum levels in comparison
      with asymptomatic hepatitis B virus (HBV) carriers. The findings showed that the
      thymol turbidity test (TTT) values and zinc sulfate turbidity test (ZTT) values
      were significantly higher in asymptomatic HCV carriers than in asymptomatic HBV
      carriers, whose values were within the normal limits. Multivariate analysis
      showed that the independent predictor of serum TTT and ZTT levels was the HCV
      infection. In clinical state, simple and cheap tests such as TTT and ZTT are
      useful for mass screening to detect HCV carriers in medical check-ups of healthy
      workers.

PMID- 11470630
TI  - Transcription-mediated amplification is more useful in the follow-up of patients
      with chronic hepatitis B treated with lamivudine.
AB  - Changes in the HBV DNA level during the treatment of patients with chronic
      hepatitis B with lamivudine were investigated by the transcription-mediated
      amplification (TMA) assay. Twenty-four patients treated with lamivudine
      (males:female= 20:4, age: 44.0+/-9.0 years, chronic hepatitis: 14, cirrhosis: 7,
      cirrhosis with hepatocellular carcinoma: 3) were investigated. The dosage of
      lamivudine was 75 mg/day in 3, 100 mg/day in 8, and 150 mg/day in 13 patients,
      and the administration period was 48+/-16 weeks (24-79 weeks). Sixteen patients
      were HBe antigen-positive before treatment, and the HBV DNA level was 7.4+/-1.2
      (4.0- more than 8.7) LGE/ml. The HBV DNA level was measured every 1-6 months by
      the TMA assay and the branched DNA signal amplification technology (b-DNA assay).
      Serum HBV DNA disappeared in all patients by the b-DNA during the treatment
      period, while six patients had persistent HBV DNA by the TMA. The time of HBV DNA
      disappearance by the TMA in 18 patients was 2-5 months after initiation of
      treatment. The disappearance rate of HBV DNA was 3/8 (38%) in patients whose HBV
      DNA level before treatment was 8.0 LGE/ml or higher, 7/8 (88%) in those with 7
      7.9 LGE/ml, and 8/8 (100%) in those with 6.9 LGE/ml or lower, showing that
      disappearance of HBV DNA became difficult when the HBV DNA level before treatment
      was high (P<0.01). In six patients, the HBV DNA level disappeared once, then
      increased thereafter. The present findings suggested that these increases in the
      HBV DNA level were due to an increase of YMDD mutant in three of these six
      patients, and due to a decrease in the dosage in two patients. In treatment with
      lamivudine, the TMA assay is more useful for understanding the changes in the HBV
      DNA level than b-DNA assay.

PMID- 11470631
TI  - TT virus infection in cases of fulminant hepatic failure-evaluation by clonality
      based on amino acid sequence of hypervariable regions.
AB  - The significance of TT virus (TTV) infection in the pathogenesis of acute liver
      disease is uncertain. Serum TTV-DNA was determined by polymarase-chain reaction
      (PCR) methods using both hemi-nested (NG059/NG063 and NG061/NG063) and single
      step (T801/T935) primers in four patients with fulminant hepatic failure and one
      patient with late onset hepatic failure in whom hepatitis A virus (HAV) and
      hepatitis B virus (HBV) markers were negative. Of these five patients, the TTV
      DNA was positive in two patients with fulminant hepatic failure by both PCRs
      before receiving blood transfusion and/or blood-products infusion. Therapies
      including plasma exchange with blood hemodiafiltration was performed in both
      patients, and one survived. The non-survivor was an 18-year-old woman with TTV
      genotype 2 infection. In this patient, the TTV-DNA by PCRs with both primers was
      positive transiently when serum ALT levels were elevated. The survivor was a 78
      year-old woman with infections of TTV genotype 1b and hepatitis C virus (HCV), in
      whom serum ALT levels returned to normal at 3 weeks after the start of the
      therapies, but fluctuated after 10 weeks. TTV-DNA measured by hemi-nested primers
      and HCV-RNA were negative when serum ALT levels decreased, but became positive
      later. Semi-quantitative PCR using single-step primers revealed that serum TTV
      DNA levels changed in correlation with both serum ALT and HCV-RNA levels. Amino
      acid sequences of hypervariable regions were identical in six out of nine clones
      isolated from the sera before the therapies and sequence divergence was minimal
      even in the other three clones, suggesting that TTV proliferated with clonality
      in the process of fulminant hepatic failure. We conclude that clonally
      proliferating TTV may contribute to fulminant hepatic failure as a solitary
      infectious agent or a co-infectious agent with HCV.

PMID- 11470633
TI  - [Revising the concept of reference values: a necessity].

PMID- 11470634
TI  - [Molecular basis of oncogenesis].
AB  - After a quarter century of rapid advances, cancer research has generated a rich
      and complex body of knowledge, revealing cancer to be a disease involving dynamic
      changes in the genome. Several lines of evidence indicate that tumorigenesis in
      humans is a multistep process and that these steps reflect genetic alterations
      that drive the progressive transformation of normal human cells into highly
      malignant derivatives. The barriers to development of cancer are embodied in a
      teleology: cancer cells have defects in regulatory circuits that govern normal
      cell proliferation and homeostasis. This review concern the description of novel
      capabilities acquired during tumor development.

PMID- 11470635
TI  - [Chronic lymphoid hemopathies in adults: chronic lymphocytic leukaemia and the
      phase of dissemination of small cell lymphomas].
AB  - Chronic lymphocytic leukaemia is the most frequent haematological cancer in adult
      patients, and its incidence raises with aging. Diagnosis needs several clinical
      and biological data, but hemogram together with the morphological and
      immunophenotypic analysis of the lymphoid cells take the major place. If the
      diagnosis is performed easily in about 65% of the patients, various
      clinicobiological entities were reported in the past few years that must be
      identified, at least because some are of adverse prognosis. Moreover, the other
      chronic lymphoid neoplasms, corresponding to the various low and intermediate
      grade non-Hodgkin's lymphomas (mainly of follicular type, marginal zone, mantle
      cell zone), may disseminate within the blood and the bone marrow. Those
      circulating lymphoma cells must be identified at diagnosis in order to perform
      the accurate diagnosis and to avoid an erroneous diagnosis of atypical chronic
      lymphocytic leukaemia. Up to 90% of lymphoid malignancies are B cell disorders,
      contrasting with only a few cases of T cell origin: some of those latter cases
      cannot be neglected however, as they may be observed in Western countries. Most
      recent classifications (REAL and WHO) defined all hematological malignancies:
      each entity referred to clinical, morphological, immunological, cytogenetic, and
      molecular findings. The basis of these classifications is pathophysiological,
      trying in each disorder to define a normal counterpart to the pathological clone.
      Reviewing main steps of the immune response in the normal patient, corresponding
      to those involving B cells, it is possible indeed to localize and demonstrate a
      function for many of the cells that expand in lymphoid malignancies.

PMID- 11470636
TI  - [Effects of vitamin A supplementation on nutritional markers on the follow-up of
      malnutrition in children].
AB  - Prospectively assessment of vitamin A supplemented during a follow-up of a
      protein-energy malnutrition rehabilitation included serum retinol, Retinol
      Binding Protein (RBP) and prealbumin (PA) determination. This study was conducted
      during one month on a group of 36 vitamin A (200,000 IU) supplemented
      malnourished children and 32 age-and sex-matched malnourished children receiving
      only a nutritional regimen. Determinations were carried out at days 0, 15 and 30.
      Protein marker concentrations increased steadily in supplemented children as
      compared to those in the untreated group (p < 0.05, Student's t test). On the
      other hand, serum concentrations of the two proteins progressively regained
      normal values in the vitamin A supplemented group. Data also showed that retinol
      supplementation in conjunction with an appropriate nutritional diet is effective
      in raising serum concentrations of vitamin A and its binding proteins to normal
      levels. Therefore, we concluded that the results of this study demonstrates the
      importance of vitamin A supplementation in the management of these deficiency
      states.

PMID- 11470637
TI  - [Heparin induced autoimmune thrombocytopenia: assessment of a rapid functional
      assay].
AB  - Heparin-induced thrombocytopenia (HIT) diagnosis is often difficult. Depending on
      the patients, the thrombocytopenia could be due to various causes. Despite their
      poor sensitivity and specificity, biological tests are necessary to clarify the
      diagnosis. In 1985, a new heparin-induced platelet aggregation assay was
      described that consists in determining the percentage of aggregated platelets by
      using an automated cell counter. Plasma samples from 18 patients with a definite
      HIT were tested with this quick easy-to-perform HIT diagnosis test. Positive
      results were obtained with 11 plasma (61%) when the test was performed with
      platelets from 3 different healthy volunteers (control platelets). As for the
      other functional tests, results are depending on control platelets and
      sensitivity seems to be increased when control platelets FcgammaRIIa-131
      polymorphism was of His/His (but difference is not significant). In emergency
      situation, it is difficult to perform a functional test with control platelets
      from several healthy donors, and it is even more difficult to select volunteers
      on their FcgammaRIIa-131 polymorphism. In conclusion, in spite of its
      practicability, the test is not reliable to help in the rapid diagnosis of HIT.
      Indeed, 7 patients of 18 (39%) with definite HIT have been found negative with
      this test.

PMID- 11470638
TI  - [Genetics and aging].

PMID- 11470639
TI  - [Neuroendocrine aging].

PMID- 11470640
TI  - [Nutrition in the elderly: importance and traps of biological investigations].

PMID- 11470641
TI  - [Aging and oxidative stress. Which potential markers?].

PMID- 11470642
TI  - [The immune systeme in the aging].

PMID- 11470643
TI  - [Homocysteine and prevention of cardiovascular diseases in the elderly].

PMID- 11470644
TI  - [CRP and cardiovascular prevention in the elderly].

PMID- 11470645
TI  - [Which biology to prevent osteoporosis in the elderly?].

PMID- 11470646
TI  - [Conclusion and perspectives].

PMID- 11470647
TI  - [Do not forget hand, foot and mouth disease when confronted with a vesicular
      eruption].

PMID- 11470648
TI  - [The internet and biology].

PMID- 11470649
TI  - [About a case of chronic autoimmune thrombocytopenic purpura associated with
      toxoplasmosis].

PMID- 11470650
TI  - [In vitro EDTA-dependent lymphocyte agglutination].

PMID- 11470651
TI  - [Procalcitonin level in deep-seated Candida infections].

PMID- 11470652
TI  - [Recommendations for setting up and using point of care blood gas systems].

PMID- 11470653
TI  - [Prognostic value of hypercoagulability in cancer patients].

PMID- 11470656
TI  - Physiological and morphological adaptations of the fruit tree Ziziphus
      rotundifolia in response to progressive drought stress.
AB  - The physiological basis of drought resistance in Ziziphus rotundifolia Lamk.,
      which is an important, multipurpose fruit tree of the northwest Indian arid zone,
      was investigated in a greenhouse experiment. Three irrigation regimes were
      imposed over a 34-day period: an irrigation treatment, a gradual drought stress
      treatment (50% of water supplied in the irrigation treatment) and a rapid drought
      stress treatment (no irrigation). Changes in gas exchange, water relations,
      carbon isotope composition and solute concentrations of leaves, stems and roots
      were determined. The differential rate of stress development in the two drought
      treatments did not result in markedly different physiological responses, but
      merely affected the time at which they were expressed. The initial response to
      decreasing soil water content was reduced stomatal conductance, effectively
      maintaining predawn leaf water potential (Psi(leaf)), controlling water loss and
      increasing intrinsic water-use efficiency, while optimizing carbon gain during
      drought. Carbon isotope composition (delta13C) of leaf tissue sap provided a more
      sensitive indicator of changes in short-term water-use efficiency than delta13C
      of bulk leaf tissue. As drought developed, osmotic potential at full turgor
      decreased and total solute concentrations increased in leaves, indicating osmotic
      adjustment. Decreases in leaf starch concentrations and concomitant increases in
      hexose sugars and sucrose suggested a shift in carbon partitioning in favor of
      soluble carbohydrates. In severely drought-stressed leaves, high leaf nitrate
      reductase activities were paralleled by increases in proline concentration,
      suggesting an osmoprotective role for proline. As water deficit increased, carbon
      was remobilized from leaves and preferentially redistributed to stems and roots,
      and leaves were shed, resulting in reduced whole-plant transpiration and enforced
      dormancy. Thus, Z. rotundifolia showed a range of responses to different drought
      intensities indicating a high degree of plasticity in response to water deficits.

PMID- 11470657
TI  - Water use by whitebark pine and subalpine fir: potential consequences of fire
      exclusion in the northern Rocky Mountains.
AB  - In subalpine forests of the northern Rocky Mountains, fire exclusion has
      contributed to large-scale shifts from early-successional whitebark pine (Pinus
      albicaulis Engelm.) to late-successional subalpine fir (Abies lasiocarpa (Hook.)
      Nutt.), a species assumed to be more shade tolerant than whitebark pine and with
      leaf to sapwood area ratios (A(L):A(S)) over twice as high. Potential
      consequences of high A(L):A(S) for subalpine fir include reduced light
      availability and, if hydraulic sufficiency is maintained, increased whole-tree
      water use. We measured instantaneous gas exchange, carbon isotope ratios and sap
      flow of whitebark pine and subalpine fir trees of different sizes in the Sapphire
      Mountains of western Montana to determine: (1) whether species-specific
      differences in gas exchange are related to their assumed relative shade tolerance
      and (2) how differences in A(L):A(S) affect leaf- and whole-tree water use.
      Whitebark pine exhibited higher photosynthetic rates (A = 10.9 micromol x m(-2) x
      s(-1) +/- 1.1 SE), transpiration rates (E = 3.8 mmol x m(-2) x s(-1) +/- 0.7 SE),
      stomatal conductance (g(s) = 166.4 mmol x m(-2) x s(-1) +/- 5.3 SE) and carbon
      isotope ratios (delta13C = -25.5 per thousand +/- 0.2 SE) than subalpine fir (A =
      5.7 micromol x m(-2) x s(-1) +/- 0.9 SE; E = 1.4 mmol x m(-2) x s(-1) +/- 0.3 SE;
      g(s) = 63.4 mmol x m(-2) x s(-1) +/- 1.2 SE, delta13C = -26.2 per thousand +/-
      0.2 SE; P < 0.01 in all cases). Because subalpine fir had lower leaf-area-based
      sap flow than whitebark pine (QL = 0.33 kgx m(-2) x day(-1) +/- 0.03 SE and 0.76
      kg x m(-2) x day(-1) +/- 0.06 SE, respectively; P < 0.001), the higher A(L):A(S)
      in subalpine fir did not result in direct proportional increases in whole-tree
      water use, although large subalpine firs used more water than large whitebark
      pines. The linear relationships between tree size and daily water use (r2 = 0.94
      and 0.97 for whitebark pine and subalpine fir, respectively) developed at the
      Sapphire Mountains site were applied to trees of known size classes measured in
      12 natural subalpine stands in the Bob Marshall Wilderness Complex (western
      Montana) ranging from 67 to 458 years old. Results indicated that the potential
      for subalpine forests to lose water by transpiration increases as succession
      proceeds and subalpine fir recruits into whitebark pine stands.

PMID- 11470658
TI  - Family differences in height growth and photosynthetic traits in three conifers.
AB  - We investigated variation in height growth, gas exchange, chlorophyll
      fluorescence and leaf stable carbon isotope ratio among wind-pollinated progenies
      of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. glauca), ponderosa pine
      (Pinus ponderosa Dougl. ex Laws.) and western white pine (Pinus monticola Dougl.
      ex D. Don) from a small group of contiguous stands on the Priest River
      Experimental Forest in northern Idaho. Photosynthetic variables differed between
      height classes in the pines, but not in Douglas-fir. Among species and families,
      tall families of ponderosa pine regained photosynthetic capacity earliest in the
      spring and maintained it latest in the growing season. Tall families of western
      white pine had higher instantaneous water-use efficiencies and lower
      photosynthetic rates than short families on warm days in August.

PMID- 11470659
TI  - Variation in surface conductance to water vapor diffusion in peach fruit and its
      effects on fruit growth assessed by a simulation model.
AB  - Surface conductance to water vapor diffusion was measured in individual peach
      fruits (Prunus persica (L.) Batsch) and plotted as a function of fresh fruit mass
      for four cultivars. Surface conductance increased with fresh fruit mass, but the
      pattern differed with cultivar, and fruit-to-fruit variation occurred.
      Relationships between fruit mass and surface conductance were modeled by fitting
      mathematical equations to the data. The simulation model of Fishman and Genard
      (1998) was used to study dry mass and water components of fruit growth (1) when
      surface conductance varied with fruit size or was constant, and (2) when surface
      conductance values were high, moderate or low with respect to fruit mass.
      Increased surface conductance with fresh fruit mass resulted in fruit growth
      cessation. Fruits differing in surface conductance had similar dry mass. However,
      under well-watered conditions (stem water potential between -1 and -0.2 MPa), the
      water balance components of growth (osmotic and hydrostatic pressure, water
      potential and water balance) differed greatly and, as a result, the lower the
      surface conductance the greater the fresh fruit mass. These differences were
      buffered under drought conditions (stem water potential between -2.4 and -0.6
      MPa).

PMID- 11470660
TI  - Variation in water relations characteristics of terminal shoots of Port-Orford
      cedar (Chamaecyparis lawsoniana) seedlings.
AB  - We measured water relations attributes of the terminal shoots of 3-year-old Port
      Orford-cedar (Chamaecyparis lawsoniana (A. Murr.) Parl.) seedlings that
      represented its geographic range. Pressure-volume curves were developed and
      osmotic potentials at full (psi(sf)) and zero turgor (psi(sz)), relative water
      content at zero turgor, and an index of tissue elasticity (IE) were calculated
      for 38 families during early, mid- and late summer at an inland nursery, and for
      12 of these families during mid- and late summer at a coastal nursery. Compared
      with other conifer species, psi(sz) was high (-1.4 to -1.5 MPa) and declined in
      seedlings at both nurseries as the season progressed. Both IE and osmotic
      amplitude (psi(sf)-psi(sz)) increased during the season. Osmotic potential at
      zero turgor was lower and osmotic amplitude greater in seedlings at the inland
      nursery than at the coastal nursery. Correlations of water relations attributes
      with geographic location of the seed sources were weak and usually not
      significant. High elevation southern sources exhibited smaller differences in
      psi(sz) between nurseries than low elevation northern sources. The small
      differences in water relations attributes among sources and between nurseries
      suggest that some may be of marginal physiological importance; however, sources
      that produced larger seedlings appeared to be less desiccation tolerant. We
      conclude that, when moving genotypes during reforestation, decisions based on
      patterns in tree size and timing of growth will account for these small
      differences in water relations.

PMID- 11470661
TI  - Fast, nondestructive measurement of frost hardiness in conifer seedlings by
      VIS+NIR spectroscopy.
AB  - Frost hardiness development from mid-August to mid-November was evaluated in
      seedlings of three provenances of Norway spruce (Picea abies (L.) Karst.) and
      three provenances of Scots pine (Pinus sylvestris L.) raised at nurseries in
      north, central and south Sweden. Measurements of the visible + near infrared
      (VIS+NIR) spectra of shoots were made simultaneously with estimates of frost
      hardiness based on electrolyte leakage following artificial freezing. Nine
      physiological variables known to influence frost hardiness were measured
      throughout the experiment. Multivariate analysis showed that VIS+NIR spectra
      explained 69% and 72% of the variation in frost hardiness in Scots pine and
      Norway spruce, respectively. Stem lignification, dry weight fraction, and starch,
      glucose, fructose, galactose, sucrose, raffinose and stachyose concentrations
      together explained 80% and 85% of the variation in frost hardiness in Scots pine
      and Norway spruce, respectively when used as independent X variables in a partial
      least squares model. These physiological variables could be related to varying
      degrees with variation in the VIS+NIR spectra. We conclude that VIS+NIR
      spectroscopy provides a rapid nondestructive technique for measuring frost
      hardiness in conifer seedlings based on causal relationships between the spectra
      and the physiology of seedling frost hardiness.

PMID- 11470662
TI  - Abscisic acid in leaves and roots of willow: significance for stomatal
      conductance.
AB  - Excised leaves and roots of willow (Salix dasyclados Wimm.) accumulated abscisic
      acid (ABA) in response to desiccation. The accumulation of ABA was greater in
      young leaves and roots than in old leaves and roots. In mature leaves, ABA
      accumulation was related to the severity and duration of the desiccation
      treatment. Water loss equal to 12% of initial fresh weight caused the ABA content
      of mature leaves to increase measurably within 30 min and to double in 2.5 h. The
      drying treatment caused significant (P = 0.05) reductions in leaf water potential
      and stomatal conductance. Recovery of leaf water potential to the control value
      occurred within 10 min of rewatering the dehydrated leaves, but recovery of
      stomatal conductance took an hour or longer, depending on the interval between
      dehydration and rewatering. The addition of ABA to the transpiration stream of
      well-watered excised leaves was sufficient to cause partial stomatal closure
      within 1 h and, depending on ABA concentration, more or less complete stomatal
      closure within 3 h. When the ABA solution was replaced with water, stomatal
      conductance increased at a rate inversely related to the concentration of the ABA
      solution with which the leaves had been supplied.

PMID- 11470663
TI  - Stomatal and leaf growth responses to partial drying of root tips in willow.
AB  - Root tips of intact willow (Salix dasyclados Wimm., Clone 81-090) plants were
      partially dried by exposure to ambient greenhouse air and then kept in water
      vapor-saturated air for up to 3 days. The drying treatment increased abscisic
      acid (ABA) concentrations in both the root tips subjected to drying and in the
      xylem sap, while it reduced leaf stomatal conductance and leaf extension rate.
      Despite the decrease in stomatal conductance, leaf water potentials were
      unaffected by the root drying treatment, indicating that the treatment reduced
      hydraulic conductivity between roots and foliage. After roots subjected to drying
      were returned to a nutrient solution or excised, ABA concentrations in the
      remaining roots and in the xylem sap, stomatal conductance of mature leaves and
      extension rate of unfolding leaves all returned to values observed in control
      plants. The 4-fold increase in xylem sap ABA concentration following the root
      drying treatment was not solely the result of reduced sap flow, and thus may be
      considered a potential cause, not merely a consequence, of the observed reduction
      in stomatal conductance.

PMID- 11470664
TI  - Acclimation of whole-plant Acacia farnesiana transpiration to carbon dioxide
      concentration.
AB  - Transpiration per unit leaf area of Acacia farnesiana (L.) Willd. plants grown at
      a CO2 concentration ([CO2]) of 385 micromol x mol(-1) was about twice that of
      plants grown at 980 micromol x mol(-1). However, whes plants grown for more than
      a year at 980 micromol x mol(-1) were exposed to 380 micromol x mol(-1) for 9
      days, they transpired at half the rate of those that had been grown at 380
      micromol x mol(-1)1. Similarly, plants grown at 380 micromol x mol(-1), when
      exposed to 980 micromol x mol(-1), transpired at twice the rate of those grown at
      980 micromol x mol(-1). Thus, the effects of elevated [CO2] on whole-plant
      transpiration, like those on photosynthesis, respiration and stomatal
      conductance, cannot reliably be extrapolated from measurements made during short
      term exposure to elevated [CO2].

PMID- 11470665
TI  - Hyperhomocystinemia.

PMID- 11470666
TI  - Local heat versus ice on blepharoptosis.

PMID- 11470669
TI  - If IOP measurement is only an estimate, then what?

PMID- 11470672
TI  - IOP in Chinese eyes.

PMID- 11470674
TI  - Target pressure.

PMID- 11470676
TI  - Superior rectus-levator synkinesis.

PMID- 11470677
TI  - Systemic beta-blocker therapy and brimonidine and timolol.

PMID- 11470678
TI  - Polyurethane stent in nasolacrimal duct obstruction.

PMID- 11470680
TI  - Mechanism of accommodation in primates.

PMID- 11470684
TI  - Subretinal fibrosis in Vogt-Koyanagi Harada syndrome.

PMID- 11470686
TI  - Multifocal intraocular lenses in children.

PMID- 11470687
TI  - Multifocal intraocular lens implantation in pediatric cataract surgery.
AB  - OBJECTIVE: To evaluate implantation of a zonal-progressive multifocal intraocular
      lens (IOL) in children. STUDY DESIGN: Prospective, noncomparative, interventional
      case series. PARTICIPANTS: Thirty-five eyes of 26 pediatric patients aged 2 to 14
      years with multifocal IOL implantation at one institution with more than 1 year
      of follow-up. INTERVENTIONS: Standard surgical procedure comprised an anterior
      capsulorrhexis, lens material aspiration via two side-port incisions, temporal
      tunnel incision, and multifocal IOL (SA40-N; Allergan, Irvine, CA) implantation
      in all eyes. In 24 eyes (68%), a 5-mm posterior capsulorrhexis was created with
      forceps, followed by an anterior vitrectomy in 19 of those eyes (54%). RESULTS:
      Twenty-six patients (35 eyes) had an average follow-up of 27.4 +/- 12.7 months
      (range, 12-58 months). At last follow-up, best-corrected distance visual acuity
      improved significantly (P = 0.001), 71% of eyes with a visual acuity of 20/40 or
      better and 31% of eyes with a visual acuity of 20/25 or better. In the 9
      bilateral cases, spectacle dependency was moderate, with only 2 children (22%)
      reporting the permanent use of an additional near correction. The remaining
      children were either using distance-correction only (4 patients; 44%) or no
      glasses at all (3 patients; 33%). Stereopsis also improved significantly after
      multifocal IOL implantation (P = 0.01). Sixteen eyes (46%) experienced
      obscuration of the entrance pupil that required intervention, with 10 requiring a
      second intraocular surgery. Four eyes required an anterior membranectomy for
      persistent fibrinous membrane. Intraocular lens decentration requiring surgical
      intervention developed in six eyes. CONCLUSIONS: Multifocal IOL implantation is a
      viable alternative to monofocal pseudophakia in this age group.

PMID- 11470688
TI  - The Berkeley Contact Lens Extended Wear Study. Part I : Study design and conduct.
AB  - OBJECTIVE: The primary aim of the Berkeley Contact Lens Extended Wear Study
      (CLEWS) was to test the hypotheses that extended wear of rigid gas-permeable
      (RGP) contact lenses with greater oxygen permeability (Dk) reduces the incidence
      of contact lens-associated keratopathy (CLAK) and increases the survival rate in
      RGP extended wear (EW). In this article we describe the clinical trial design in
      detail, present the results of subject recruitment and retention, and provide the
      baseline demographic and ocular characteristics of the CLEWS subjects, whose data
      will be analyzed to address the study aims in a companion article. DESIGN: A
      randomized, concurrently controlled clinical trial. INTERVENTION: Subjects were
      fitted with day wear (DW) high-Dk RGP lenses and then adapted to EW. Subjects who
      adapted to EW were then randomly assigned to either high- or medium-Dk RGP lenses
      for 12 months of 6-nights/week EW. MAIN OUTCOME MEASURES: Slit-lamp assessment
      and grading of 17 possible keratopathies, measurement of refractive error and
      corneal curvature, and symptoms. Follow-up data were collected every 3 months.
      RESULTS: From 545 subjects entering the DW adaptation phase, 201 adapted to EW
      and were randomly assigned to medium- or high-Dk lenses for 12 months of EW. The
      baseline characteristics of the two study groups were similar and did not differ
      from the 344 DW subjects who failed to adapt to EW. The distributions of oxygen
      transmissibility for the two study groups were disjoint, indicating that each
      group received distinctly different levels of hypoxia. CONCLUSIONS: We show that
      CLEWS was appropriately designed to address the study hypotheses, was conducted
      with regard for the safety of the subjects, and adhered to rigorous protocols
      designed to control for bias and ensure the integrity of study data. We establish
      the internal validity of between-group statistical comparisons and characterize
      our study population to permit informed evaluation of the applicability of our
      results to the contact lens-wearing population in general.

PMID- 11470689
TI  - The Berkeley Contact Lens Extended Wear Study. Part II : Clinical results.
AB  - OBJECTIVE: To describe the principal clinical outcomes associated with 12 months
      use of rigid gas-permeable (RGP) extended wear contact lenses and address two
      primary study questions: (1) does extended wear (EW) of high oxygen
      transmissibility (Dk/t) RGP lenses reduce the incidence of ocular complications,
      and (2) does the wearing of high-Dk/t lenses reduce the rate of failure to
      maintain 6-night RGPEW over 12 months? DESIGN: A randomized, concurrently
      controlled clinical trial. INTERVENTION: Subjects who adapted to EW with high Dk
      (oxygen permeability) RGP lenses were randomized to either high Dk or medium-Dk
      RGP lenses for 12 months of 6-night EW. MAIN OUTCOME MEASURES: Contact lens
      associated keratopathies (CLAK), changes in refractive error and corneal
      curvature, and survival in EW. RESULTS: Two hundred one subjects were randomized
      to medium or high-Dk lenses for 12 months of EW. Sixty-two percent of the
      subjects in each group completed 12 months of EW; however, the probability of
      failure was significantly greater for the medium-Dk group. Although the risk of
      complications was similar for the two groups, the number of CLAK events that led
      to termination were 16 versus 5 for the medium-Dk and high-Dk groups,
      respectively. This suggests that the type of adverse response or the inability to
      reverse an adverse event was different for the group being exposed to the lower
      oxygen dose. CONCLUSIONS: The level of oxygen available to the cornea has a
      significant impact on maintaining successful RGP extended contact lens wear, but
      not on the initial onset of CLAK. The number of clinical events leading to
      termination was substantially higher for the medium Dk group, which suggests that
      corneal hypoxia is an important factor in the development of CLAK. Although
      overnight contact lens wear should be recommended with caution and carefully
      monitored for early detection of ocular complications, it appears that high-Dk
      RGP lenses can be a safe and effective treatment for correction of refractive
      error for most individuals who can adapt to EW.

PMID- 11470690
TI  - Risk factors associated with age-related nuclear and cortical cataract : a case
      control study in the Age-Related Eye Disease Study, AREDS Report No. 5.
AB  - OBJECTIVE: To investigate possible risk factors for age-related nuclear and
      cortical cataracts in participants in the Age-Related Eye Disease Study (AREDS).
      DESIGN: Case-control study. PARTICIPANTS: Of the 4757 persons enrolled in AREDS,
      4477 age 60 to 80 years are included in the study. MAIN OUTCOME MEASURES: Slit
      lamp lens photographs were used to classify participants into one of three
      nuclear opacity groups (moderate nuclear, mild nuclear, and controls), ignoring
      cortical opacities. Retroillumination lens photographs were used to classify
      participants into one of three cortical opacity groups (moderate cortical, mild
      cortical, and controls), ignoring nuclear opacities. RESULTS: Persons with
      moderate nuclear opacities were more likely to be female, nonwhite, and smokers
      and to have large drusen. Moderate nuclear opacities were less common in persons
      with higher educational status, a history of diabetes, and among those taking
      nonsteroidal antiinflammatory drugs. Moderate cortical opacities were associated
      with dark iris color, large drusen, weight change, and, at a borderline level of
      significance, higher levels of sunlight exposure and use of thyroid hormones.
      Moderate cortical opacities were less common in persons with higher educational
      status. CONCLUSION: Consistent findings have now been reported across many
      studies for gender, educational status, sunlight exposure, and smoking. Our
      findings that use of nonsteroidal antiinflammatory drugs is inversely associated
      with nuclear cataract and that dark iris color and use of thyroid hormones may
      increase cortical cataract risk are less well substantiated and require further
      investigation.

PMID- 11470691
TI  - INTACS inserts for treating keratoconus: one-year results.
AB  - OBJECTIVE: To evaluate the use of INTACS micro-thin prescription inserts (Kera
      Vision, Inc., Fremont, CA) for the treatment of keratoconus. DESIGN: Prospective,
      nonrandomized (self-controlled) comparative trial. PARTICIPANTS/INTERVENTION: Ten
      patients from our prospective clinical study who had completed 12 months of
      follow-up were evaluated. All patients had keratoconus with clear central corneas
      and were contact lens intolerant. After reviewing corneal pachymetry and
      topography of individual patients, INTACS inserts of 0.45-mm thickness were
      placed in the inferior cornea to lift the cone and INTACS of 0.25-mm thickness
      were inserted superiorly to counterbalance and flatten the overall anterior
      corneal surface. MAIN OUTCOME MEASURES: Differences between preoperative and
      postoperative uncorrected visual acuity, best spectacle-corrected visual acuity,
      manifest refraction, and keratometry values were statistically assessed. Changes
      in corneal ectasia were evaluated by reviewing corneotopographic maps. RESULTS:
      No intraoperative complications occurred in this series of patients. Spherical
      equivalent error and refractive astigmatism were reduced with INTACS inserts
      treatment. Postoperative month 12 uncorrected visual acuity (logarithm of the
      minimum angle of resolution [logMAR] mean, 0.35, standard deviation [SD], 0.16
      [approximately 20/50, approximately 2 lines]) was significantly better than
      preoperative (logMAR mean, 1.05; SD, 0.33 [approximately 20/200, approximately 3
      lines]; P <or=0.05). Average best spectacle-corrected visual acuity at
      postoperative month 12 was improved by approximately two lines compared with
      baseline (logMAR mean, 0.22; SD, 0.12 [approximately 20/32, approximately 1
      line]; logMAR mean, 0.38; SD, 0.13 [approximately 20/50, approximately 1 line],
      respectively). Topographic corneal shape (size and height of the cone) was
      improved for all subjects after insert placement. CONCLUSIONS: INTACS micro-thin
      prescription inserts seem to provide a viable method for treating clear corneal
      keratoconus for patients who are contact lens intolerant. The corneal steepening
      and astigmatism associated with keratoconus were reduced, and visual acuity was
      improved with treatment in almost all eyes.

PMID- 11470692
TI  - Posterior corneal surface changes after refractive surgery.
AB  - OBJECTIVE: To determine the frequency of changes in posterior corneal surface
      after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK).
      DESIGN: Nonrandomized, comparative trial. PARTICIPANTS: Ninety-five eyes (71
      patients) that underwent PRK (n = 45) or LASIK (n = 50). CONTROLS: Twenty
      nonsurgery eyes were used to validate the method of analysis of the posterior
      corneal curvature (PCC). Seventy nonsurgery eyes were used for comparisons.
      METHODS: Float, apex-fixed best fit corneal curvature (ABC), and posterior
      elevation difference were evaluated in 20 elevation topography maps at 6 zone
      diameters (3-7 and 10 mm) and at two time points. Corneal elevation maps before
      and after PRK or LASIK were analyzed by the ABC and float methods and compared
      with a nonsurgery group. MAIN OUTCOME MEASURES: Posterior corneal curvature
      change (mm) was classified as flattening, steepening, or no change. RESULTS:
      Flattening of more than 0.12 mm was found in 22.2% of eyes (n = 10) in the PRK
      group, a change of +/-0.12 mm was found in 53.3% of eyes (n = 24), and steepening
      of more than 0.12 mm was found in 24.4% of eyes (n = 11) using the float method
      and in 28.9% of eyes (n = 13), 35.6% of eyes (n = 16), and 35.6% eyes (n = 16),
      respectively, using the ABC method. In the LASIK group, the float method
      registered flattening in 20% of eyes (n = 10), no change in 52% of eyes (n = 26),
      and steepening in 28% of eyes (n = 14), whereas the ABC method registered
      flattening in 30% of eyes (n = 15), no change in 40% of eyes (n = 20), and
      steepening in 30% of eyes (n = 15). The nonsurgery group showed a similar change
      in PCC at two different time points similar to that of the PRK and the LASIK
      groups. CONCLUSIONS: The differences observed in the PCC after PRK or LASIK were
      not statistically significantly different from those observed over time in the
      nonsurgery control group.

PMID- 11470693
TI  - Laser in situ keratomileusis enhancement after photorefractive keratectomy.
AB  - OBJECTIVE: To describe the safety, effectiveness, and predictability of laser in
      situ keratomileusis (LASIK) for correcting residual myopia after primary
      photorefractive keratectomy (PRK). DESIGN: A retrospective, noncomparative case
      series. PARTICIPANTS AND INTERVENTION: Thirty-six consecutive eyes of 30 patients
      underwent LASIK after primary PRK. A Multiscan Schwind excimer laser was used for
      LASIK enhancement. MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), best
      spectacle-corrected visual acuity, refraction, videokeratography, and
      complications were determined before and after LASIK retreatment. Follow-up was
      at least 12 months. RESULTS: Before LASIK, 11.11% of eyes showed a UCVA of 20/40
      or better. This increased to 94.44% 12 months after LASIK. A UCVA of 20/25 or
      better was achieved in 0% before and in 72.22% after retreatment. Refraction +/
      0.5 diopters (spherical equivalent) represented 0% of eyes before and 77.78% of
      eyes after enhancement. Before LASIK, two eyes had significant haze. Haze
      remained in these two eyes and appeared in another eye. CONCLUSIONS: Laser in
      situ keratomileusis proved to be safe and effective for treating residual myopia
      after PRK. Care must be taken when considering LASIK retreatment in patients with
      significant haze after primary PRK.

PMID- 11470695
TI  - Monovision outcomes in presbyopic individuals after refractive surgery.
AB  - PURPOSE: To characterize monovision outcomes and patient satisfaction with
      conventional monovision (dominant eye corrected for distance) and crossed
      monovision (dominant eye corrected for near) in presbyopic individuals after
      excimer laser photorefractive keratectomy (PRK) and laser in situ keratomileusis
      (LASIK). DESIGN: Retrospective observational case series. PARTICIPANTS: One
      hundred forty-four consecutive patients, 45 years or older, who were treated with
      excimer laser refractive surgery between December 1995 and June 1998. METHODS:
      Patients in whom the surgical outcome was monovision (MV) (distance vision
      spherical equivalent [SE] -0.50 to +0.50 diopter (D), near vision SE -3.75 to 
      1.00 D and anisometropia 1.00 D or greater), crossed MV (dominant eye corrected
      for near vision and the nondominant eye for distance vision) and full correction
      (bilateral SE -0.50 to +0.50) were identified. Data were abstracted and analyzed
      statistically. MAIN OUTCOME MEASURES: Preoperative and postoperative visual
      acuity and refraction. Patient satisfaction with monovision RESULTS: Forty-two
      patients had surgical outcome of MV. In MV patients, the average distance vision
      SE, near vision SE, and anisometropia were -0.04 +/- 0.27 D, -1.95 +/- 0.70 D,
      and 1.92 +/- 0.74 D, respectively. Patient satisfaction was 88% with MV. Twelve
      patients attained crossed MV. All patients with crossed MV were satisfied with
      their vision. Patient satisfaction with MV showed no relationship to gender, age
      at initial surgery, preoperative trial of monovision, laterality of treatment,
      type of monovision, or predictability of outcomes. CONCLUSIONS: Monovision may be
      a valuable option for presbyopic individuals considering refractive surgery.
      Crossed monovision can result in satisfactory visual outcomes.

PMID- 11470696
TI  - The adverse effect of perioperative brimonidine tartrate 0.2% on flap adherence
      and enhancement rates in laser in situ keratomileusis patients.
AB  - PURPOSE: To investigate the effect of perioperative brimonidine tartrate 0.2% on
      postoperative flap adherence and enhancement rates in patients undergoing laser
      in situ keratomileusis (LASIK). DESIGN: Noncomparative interventional case
      series. PARTICIPANTS: Records of 279 eyes of 144 consecutive patients who
      underwent LASIK between June 17, 1999, and March 1, 2000, were retrospectively
      reviewed. METHODS: From September 28, 1999, to November 4, 1999, 39 eyes of 20
      consecutive patients had a single drop of brimonidine tartrate 0.2% instilled
      into their operative eye(s) before LASIK. This group was interposed in time
      between two nonbrimonidine groups, one before the use of brimonidine, "prior
      nonbrimonidine group" (107 eyes of 56 patients), and one after the use of
      brimonidine, "post nonbrimonidine group" (133 eyes of 68 patients). All 279 eyes
      in the study were examined after surgery to identify flap folds and dislocations.
      Enhancement rates and visual outcomes for the brimonidine and nonbrimonidine
      groups were also documented. MAIN OUTCOME MEASURES: Comparison of the incidence
      of abnormal flap appearance and enhancement rates between the brimonidine and the
      nonbrimonidine groups. RESULTS: In the brimonidine treated group, 6 of 39 eyes
      (15.4%) had an abnormal flap appearance after LASIK, although no flap folds or
      dislocations were noted in the nonbrimonidine groups. The difference in incidence
      of abnormal flap appearance between the brimonidine group and the prior and post
      nonbrimonidine groups was statistically significant (P = 0.0008 and P = 0.0003,
      respectively). When the prior and post nonbrimonidine groups were combined and
      compared with the brimonidine group, the difference in flap adherence was highly
      statistically significant (P = 0.00001). The enhancement rate was significantly
      higher in the brimonidine group at 36% compared with 14% in the prior
      nonbrimonidine group (P = 0.01) and 9% in the post nonbrimonidine group (P =
      0.0004). The mean 3-month postoperative spherical equivalent was significantly
      greater at -0.88 diopters (D) in the brimonidine group compared with -0.24 D (P =
      0.0008) and -0.15 D (P = 0.0001) in the prior nonbrimonidine and post
      nonbrimonidine groups, respectively. CONCLUSIONS: In this study, when
      perioperative topical brimonidine was used in LASIK patients, an increase in the
      incidence of abnormal flap adherence and an increase in enhancement rates was
      observed.

PMID- 11470697
TI  - Intraocular pressure over 24 hours after repeated administration of latanoprost
      0.005% or timolol gel-forming solution 0.5% in patients with ocular hypertension.
AB  - PURPOSE: To compare the effect on intraocular pressure (IOP) over 24 hours after
      4 weeks of treatment with latanoprost 0.005% and timolol gel 0.5%. DESIGN:
      Randomized, open, crossover single-center study. PARTICIPANTS: Twenty-seven
      patients with ocular hypertension. METHODS: The patients were randomly assigned
      to 4 weeks of latanoprost 0.005% once daily or timolol gel 0.5% once daily, with
      a 4-week washout period before switching therapy. MAIN OUTCOME MEASURES:
      Measurement of IOP during 24 hours of hospitalization. Blood pressure and heart
      rate were also measured repeatedly over the 24 hours. Daytime mean IOP, nighttime
      mean IOP, and 24-hour mean IOP were calculated as IOP area under the curve (AUC)
      divided by time in hours. RESULTS: The mean IOP during daytime (7 AM to 10 PM)
      was 13.5 +/- 0.4 mmHg (daytime IOP, AUC/15 hours, least square mean +/- standard
      error of the mean [SEM]) in the latanoprost group, and 14.8 +/- 0.4 mmHg in the
      timolol gel group. This difference of 1.3 +/- 0.3 mmHg was statistically
      significant in favor of latanoprost (P < 0.001; 95% confidence interval [CI],
      0.7, 2.0). The mean IOP at night (10 PM to 7 AM) was 13.7 +/- 0.4 mmHg for
      latanoprost (nighttime IOP, AUC/9 hours, least square mean +/- SEM) and 15.9 +/-
      0.5 mmHg for timolol gel, with a difference of 2.2 +/- 0.3 mmHg (P < 0.001; 95%
      CI, 1.5, 2.8). At every measured time point during the 24 hours, latanoprost
      reduced IOP more than timolol. There was no difference between the two treatment
      groups regarding blood pressure and heart rate. CONCLUSIONS: Latanoprost reduced
      mean 24-hour IOP, mean daytime IOP, and mean nighttime IOP statistically
      significantly more than timolol. Also, latanoprost reduced IOP more effectively
      at every measured time point over the 24 hours compared with timolol gel.

PMID- 11470698
TI  - Color Doppler imaging study of retrobulbar hemodynamics in chronic angle-closure
      glaucoma.
AB  - PURPOSE: To evaluate the retrobulbar hemodynamics in patients with chronic angle
      closure glaucoma (CACG) by using color Doppler imaging (CDI) and to correlate the
      degree of glaucomatous visual field loss with the hemodynamic parameters. DESIGN:
      Prospective case series. PARTICIPANTS AND CONTROLS: Twenty-six Chinese patients
      with CACG and 26 age-matched and gender-matched normal subjects were recruited.
      All CACG patients had history of chronic intraocular pressure (IOP) elevation and
      asymmetric visual field defects between their fellow eyes. After receiving laser
      peripheral iridotomy and/or filtration surgery, all of them had bilateral
      medication-free controlled IOP before enrolling into the study. METHODS: Each
      subject underwent CDI measurement in the central retinal artery (CRA) and the
      nasal and temporal short posterior ciliary arteries (PCA). Visual fields of the
      CACG patients were obtained with Humphrey 24-2 program. The visual field defects
      were scored with the Advanced Glaucoma Intervention Study (AGIS) system. For each
      CACG patient, the eye with lower AGIS score was defined as the better eye and the
      eye with higher score as the worse eye. MAIN OUTCOME MEASURES: Peak-systolic
      velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) were
      determined. RESULTS: The EDV in the CRA and the temporal PCA was decreased
      significantly (P = 0.041 and 0.023, respectively) in the worse eyes of CACG
      patients compared with those in the control eyes. The better eyes of CACG
      patients showed no significant change in hemodynamic parameters compared with the
      control eyes. While comparing the fellow eyes of CACG patients, the worse eyes
      had significantly lower EDV in the temporal PCA (P = 0.012) than the
      contralateral better eyes. In 11 CACG patients with a difference of at least 8 in
      AGIS visual field scores between their fellow eyes, the worse eyes had
      significantly lower EDV (P = 0.041) in the CRA and lower PSV (P = 0.018) and EDV
      (P = 0.018) in the temporal PCA compared with those in the contralateral eyes. In
      multivariate regression analysis, the AGIS scores were significantly correlated
      with the PSV in the CRA (P = 0.015) and with the EDV (P < 0.001) and RI (P =
      0.027) in the temporal PCA in patients with CACG. CONCLUSIONS: Patients with well
      controlled CACG may have decreased retrobulbar blood flow velocities and
      increased vascular resistance in the CRA and temporal PCA. The degree of
      retrobulbar hemodynamic impairment was well correlated with the degree of
      glaucomatous visual field loss.

PMID- 11470699
TI  - Two unusual osteogenic orbital tumors: presumed parosteal osteosarcomas of the
      orbit.
AB  - OBJECTIVE: To report two cases of suspected parosteal osteosarcoma of the orbit,
      with dedifferentiation into a high-grade liposarcoma occurring in one patient.
      DESIGN: Two retrospective case reports. METHODS: The clinical, radiologic, and
      pathologic records of two patients with suspected orbital parosteal osteosarcoma
      were retrospectively reviewed. MAIN OUTCOME MEASURES: Histologic evaluation and
      clinical follow-up were measured. RESULTS: The first patient was a 47-year-old
      male presenting with a 5-month history of painless right lower lid swelling;
      excision biopsy suggested a well-differentiated parosteal osteosarcoma of the
      orbital floor, which recurred 3 years later. Six months after excision of the
      recurrence, the mass demonstrated accelerated growth, and a lid-sparing
      exenteration was performed; histologic examination showed a high-grade
      liposarcoma. The patient remains disease-free at 4 years. The second patient, a
      40-year-old male, presented with an 8-year history of proptosis and a right
      superotemporal orbital mass. The mass was excised completely at lateral
      orbitotomy; histologic examination suggested a well-differentiated parosteal
      osteosarcoma. The patient remains well 9 months postoperatively. CONCLUSIONS:
      Parosteal osteosarcoma is an uncommon tumor, usually affecting long bones, that
      is extremely rare in the orbit. It is a low-grade sarcoma that tends to recur
      locally after excision but has a favorable prognosis. Dedifferentiation into a
      high-grade sarcoma occasionally occurs in parosteal osteosarcoma, but
      transformation into liposarcoma does not seem to have been previously reported.
      It is important to recognize dedifferentiated parosteal osteosarcoma, because the
      prognosis is poor, and radical treatment may be required.

PMID- 11470700
TI  - Predictors of nonrecovery in acute traumatic sixth nerve palsy and paresis.
AB  - PURPOSE: To evaluate whether nonrecovery from acute traumatic sixth nerve palsy
      could be predicted from demographic factors or palsy characteristics. DESIGN:
      Prospective, observational case series SETTING: Multicenter (academic and private
      practices). OUTCOME MEASURE: Nonrecovery, defined as the presence of diplopia in
      primary position or more than 10 prism diopters of distance esotropia in primary
      position at 6 months after onset. METHODS: Using data from a previously described
      cohort of 84 eligible patients with acute traumatic sixth nerve palsy, we
      performed multivariate analyses of demographic factors and palsy characteristics.
      RESULTS: Nonrecovery at 6 months after onset was associated with a complete palsy
      (adjusted risk ratio, 9.11; 95% confidence interval [CI], 2.77-14.84) and with a
      bilateral palsy or paresis (adjusted risk ratio, 2.53; 95% CI, 0.98-4.29). The
      choice of conservative management (observation, prism, or patch) versus acute
      injection of Botulinum toxin (within 3 months of injury) did not influence final
      recovery. CONCLUSIONS: In acute traumatic sixth nerve palsy or paresis, failure
      to recover by 6 months after onset was associated independently with inability to
      abduct past midline at presentation and bilaterality. Although the overall
      recovery rate is high in acute traumatic sixth nerve palsy or paresis, a complete
      or bilateral case has a poor prognosis and is more likely to need strabismus
      surgery.

PMID- 11470701
TI  - Role of transesophageal echocardiography in the evaluation of patients with
      retinal artery occlusion.
AB  - OBJECTIVE: To evaluate the role of transesophageal echocardiography (TEE) in
      detecting cardiac and thoracic aortic sources of retinal emboli. DESIGN:
      Retrospective observational case series. PARTICIPANTS: The study population
      consisted of 18 patients who were initially seen with retinal artery occlusion (7
      central, 11 branch) and underwent TEE as part of the systemic evaluation.
      INTERVENTION: All patients underwent TEE, consisting of complete two-dimensional
      and Doppler color flow examinations. TEE was done immediately after transthoracic
      echo (TTE) examination. The medical records were reviewed. MAIN OUTCOME MEASURE:
      Detection of a possible cardiac or thoracic aortic source of retinal embolus.
      RESULTS: Cardiac or thoracic aortic pathologic conditions, which were a possible
      source of the retinal emboli, were detected by TEE in 13 of the 18 patients
      (72%). They included aortic arch atheroma (n = 7), mitral annulus calcification
      (n = 4), left atrial appendage thrombus (n = 2), valvular abnormalities (n = 5),
      left atrial smoke (n = 3), and patent foramen ovale (n = 3). In 11 patients
      (61%), at least one cardiac or aortic source of emboli detected by TEE was missed
      by TTE. Significant carotid artery disease (>or=40% stenosis) was present in 3 of
      16 patients (17%). CONCLUSIONS: TEE is a potentially useful modality for
      detecting possible sources of retinal artery emboli and may be considered as an
      adjunct to the routine evaluation of affected patients.

PMID- 11470702
TI  - Cornea sparing by endoscopically guided vitreoretinal surgery.
AB  - PURPOSE: To report a series of eyes with acute severe corneal edema and
      vitreoretinal complications treated with endoscopic vitreous surgery without a
      keratoprosthesis to the cornea. DESIGN: Retrospective, small, noncomparative case
      series. PARTICIPANTS: Seven patients with unilateral acute severe corneal edema,
      poor view of the fundus, and vitreoretinal complications were reviewed. Five eyes
      were postcataract surgery, one eye was postpenetrating intraocular blunt trauma
      by a ferrous foreign body, and one eye had endophthalmitis. INTERVENTION:
      Vitreous surgery was performed on each eye under the guidance of endoscopy.
      Topical steroid treatment was administered to the cornea for several weeks after
      the vitreoretinal surgery, until the corneal edema had been completely resolved.
      MAIN OUTCOME MEASURES AND RESULTS: The edematous corneas recovered within an
      average of 9 weeks (range, 6-13 weeks). The preoperative visual acuity ranged
      from 6/90 to hand motion at 0.5 m, and the final postoperative visual acuity was
      6/30 or better after an average follow-up of 14 months (range, 3-23 months).
      CONCLUSIONS: (1) Endoscopic surgery for vitreoretinal complications in eyes with
      acute severe corneal edema can obviate keratoprosthesis and keratoplasty. (2) By
      minimizing further damage to the corneal endothelium, endoscopic vitreoretinal
      surgery might benefit corneal recovery.

PMID- 11470703
TI  - Internal limiting membrane peeling in macular hole surgery.
AB  - PURPOSE: To evaluate prospectively the ability to peel epiretinal membranes and
      to correlate the degree of membrane peeling to anatomic success rates. DESIGN:
      Consecutive, noncomparative, interventional case series. PARTICIPANTS: One
      hundred ninety-three patients. METHODS: The extent of membrane peeling and other
      intraoperative features were correlated to endpoints. MAIN OUTCOME MEASURES:
      Anatomic success (inducing hole closure), visual acuity of 20/50 or better, and
      visual improvement of two or more Snellen lines. RESULTS: One hundred ninety
      three eyes were eligible for the study by virtue of having a minimum follow-up
      interval of 6 weeks. The overall anatomic success rate was 93% in these cases.
      There was a two-line or more improvement in 72%; 56% attained 20/50 or better
      visual acuity. The internal limiting membrane was peeled completely in 23%,
      partially in 43%, and not at all in 34%. The degree of internal limiting membrane
      peeling was not correlated with the duration of the hole or rate of two-line
      visual improvement, but was inversely correlated with the rate of anatomic
      success (P = 0.045). Final visual acuity was correlated with a better
      preoperative visual acuity, shorter preoperative duration of macular hole, and
      more complete internal limiting membrane peeling. CONCLUSIONS: Peeling of the
      internal limiting membrane is not essential for anatomic or visual success in
      macular hole surgery, but it may be a means to standardize inducement of the
      proper degree of gliosis. Excessive, unsuccessful attempts at internal limiting
      membrane peeling may decrease visual success. Techniques delivering a more
      reproducible, complete, atraumatic peeling of the internal limiting membrane
      should be studied.

PMID- 11470705
TI  - Null mutation in the human 11-cis retinol dehydrogenase gene associated with
      fundus albipunctatus.
AB  - PURPOSE: Recent studies show that mutations in the gene encoding 11-cis retinol
      dehydrogenase are associated with fundus albipunctatus. The authors wanted to
      investigate whether additional, more severe, mutations in the 11-cis retinol
      dehydrogenase gene might be responsible for more severe forms of hereditary
      retinal diseases. DESIGN: Case-control molecular genetics study. PARTICIPANTS AND
      CONTROLS: Two index patients, 7 relatives, and 50 control individuals. METHODS:
      The authors screened two index patients diagnosed with fundus albipunctatus for
      mutations in exons 2 to 5 and exon/intron boundaries of the 11-cis retinol
      dehydrogenase gene by direct sequencing. Control individuals were screened for
      the presence of the mutations using allele-specific oligonucleotide
      hybridization. MAIN OUTCOME MEASURES: Mutations in exons 2 to 5 and exon/intron
      boundaries of the 11-cis retinol dehydrogenase gene. RESULTS: In a compound
      heterozygote, two novel mutations were found: a 4 bp insertion in exon 2 and a
      missense mutation Cys267Trp in exon 5. In a second pedigree, a homozygous
      frameshift mutation in codon 43 (Arg42ct[1-bpdel]) was detected. In both
      families, the mutations segregate with the disease. The mutations were not found
      in 50 control individuals. CONCLUSIONS: On the basis of our observations, it is
      unlikely that mutations in the 11-cis retinol dehydrogenase gene are associated
      with other, possibly more severe, retinal pathologic conditions/dystrophies or
      syndromic diseases in which the retina is also affected.

PMID- 11470706
TI  - Intravitreous injection of tissue plasminogen activator and gas in the treatment
      of submacular hemorrhage under various conditions.
AB  - OBJECTIVE: To investigate the efficacy and safety of treating submacular
      hemorrhages secondary to age-related macular degeneration (ARMD) with
      intravitreous recombinant tissue plasminogen activator (rt-PA) and gas under
      various conditions. DESIGN: Prospective, noncomparative case series.
      PARTICIPANTS: Forty-three consecutive eyes of 42 patients with recent (range, 2
      28 days) subfoveal hemorrhage secondary to ARMD were included in this study. The
      size of subretinal hemorrhage ranged from 0.25 to 30 disc areas. METHODS: All
      patients were treated with intravitreous injections of rt-PA (50 microg) and
      sulfur hexafluoride (0.5 ml). Postoperative prone positioning was maintained for
      24 to 72 hours. Patient follow-up ranged from 4 to 18 months (mean, 6 months).
      MAIN OUTCOME MEASURES: Best and final postoperative visual acuity in relation to
      size and onset of hemorrhage, displacement of subretinal blood, and surgical
      complications. RESULTS: Best postoperative visual acuity compared with
      preoperative visual acuity was improved two or more Snellen lines in 19 eyes
      (44%) and stable in 24 eyes (56%). Final visual acuity was improved two or more
      lines in 13 eyes (30%), stable in 26 (61%), and two or more lines worse in 4 eyes
      (9%). Duration of hemorrhage <or=14 days was associated with a better gain of
      lines of vision (P = 0.0058). Best postoperative acuity was maintained for an
      average of 4.2 months (range, 0.5-12 months). Overall, complete displacement of
      blood from under the fovea was achieved in 35 eyes (81%). Nine eyes (21%)
      developed recurrent hemorrhage, which required repeat treatment. In three
      patients (7%), a mild breakthrough vitreous hemorrhage was observed. CONCLUSIONS:
      Our findings suggest that intravitreous injections of rt-PA and gas are of value
      for an improved and accelerated visual recovery in ARMD patients with submacular
      hemorrhage, although final visual outcome is often limited by the progression of
      the underlying ARMD. Patients with retinal hemorrhages of recent onset (<or=14
      days) seem to have the most favorable results. A rapid displacement of submacular
      blood may reveal discrete choroidal neovascular membranes amenable to further
      treatment. The complication rate of this minimally invasive technique seems to be
      low.

PMID- 11470707
TI  - Vigabatrin effect on inner retinal function.
AB  - OBJECTIVE: To determine the degree of electroretinal dysfunction in a group of
      patients taking Vigabatrin (VGB). Additionally, to investigate the role of
      cumulative dosage, the role of VGB alone or in combination with other
      anticonvulsants, and whether recent discontinuance of VGB affects electroretinal
      function as measured by the electroretinogram (ERG). DESIGN: Retrospective,
      comparative case series. PARTICIPANTS: Forty patients (18 male, 22 female) with a
      mean age of 35 years were studied as three groups: the VGB multitherapy group (n
      = 24) included those taking VGB with other anticonvulsants, the VGB monotherapy
      group (n = 9) included those taking VGB alone, and the off-VGB group (n = 7)
      included those who had discontinued VGB in the last 6 months. METHODS: Scotopic
      flash, photopic flash, and 30-Hz flicker ERG results were recorded according to
      the International Society for Clinical Electrophysiology of Vision (ISCEV)
      standard. The clinical electro-oculogram (EOG) results were recorded according to
      the ISCEV standard. MAIN OUTCOME MEASURES: Implicit time and amplitudes of the A-
      and B-waves of the flash and 30-Hz flicker ERGs were recorded. Summed amplitude
      of the first three oscillatory potential wavelets were recorded. The light-peak
      to-dark-trough Arden ratio of the EOG was evaluated. RESULTS: Although photopic
      ERG B-wave reduction was most frequent in patients in the VGB multitherapy group
      (48% of eyes), a significant number of eyes in all three groups had scotopic ERG
      B-wave reduction. The 30-Hz flicker ERG result was abnormally reduced in all
      three groups. There was no significant difference in the frequency of occurrence
      in ERG result abnormalities between the VGB monotherapy and VGB multitherapy
      groups. The EOG results revealed reduced Arden ratios in all three groups;
      however, there was a significantly lower frequency of EOG abnormalities noted in
      the off-VGB group (P = 0. 0373). There was no statistically significant
      relationship between the frequency of electrodiagnostic abnormalities and the
      duration of use or the total cumulative dosage of Vigabatrin in any of the three
      groups. CONCLUSIONS: These findings of scotopic ERG result abnormalities suggest
      that VGB alone has an effect on inner electroretinal function at the level of the
      Muller cell. Concomitant EOG abnormalities suggest a substantial effect of VGB on
      outer retinal function that may be reversible after cessation of VGB treatment.

PMID- 11470709
TI  - Subclinical retinal detachment resulting from asymptomatic retinal breaks:
      prognosis for progression and regression.
AB  - PURPOSE: To give a more accurate epidemiologic description of subclinical retinal
      detachments and to learn their prognosis. DESIGN: Prospective, natural history
      cohort study. PARTICIPANTS: Seventeen patients, with 19 eyes involved with 22
      separate areas of subclinical retinal detachment (SCRD). Ages at initial
      diagnosis ranged between 14 and 67 years. METHODS: Periodic retinal examinations
      over follow-up periods of between 8 months and >33 years, using indirect
      ophthalmoscopy and scleral indentation, and sometimes slit-lamp vitreous
      examinations with Goldmann lens. MAIN OUTCOME MEASURES: Documentation with
      written descriptions and drawings of lesions and estimation of size and
      dimensions. RESULTS: The rate of progression to clinical retinal detachment
      (CRD), which involved 11% of eyes (2 of 18), was found to be exactly equal to the
      likelihood of spontaneous regression and disappearance, also found in 11% (2 of
      18), without any treatment. The calculated incidence rate of progression to CRD
      was 0.008 (<1% per year). Also, myopic females were found to have a 4.7-times
      greater risk of subclinical retinal detachment developing than were males, P =
      0.036. All of these findings are reported for the first time in the ophthalmic
      literature. CONCLUSIONS: Compared with symptomatic clinical retinal detachment,
      SCRD is much less threatening to the vision and the health of the eye. Therefore,
      SCRD does not require or justify routine treatment but should be reexamined at
      regular annual intervals or more frequently if changes are observed. If it
      definitely progresses to CRD, surgical treatment is justified.

PMID- 11470711
TI  - Ophthalmology inpatient consultation.
AB  - OBJECTIVE: To profile inpatients and eye problems evaluated and managed by the
      Ophthalmology Consultation Service of a large university teaching hospital.
      DESIGN: A hospital-based retrospective, cross-sectional study. PARTICIPANTS: One
      thousand four hundred seventy-two patients admitted to the University of
      California Los Angeles Medical Center. METHODS: We reviewed the inpatient medical
      records, discharge summaries, and Ophthalmology Consultation Service notes of
      every patient evaluated by the Service from July 1990 through January 1997. MAIN
      OUTCOME MEASURES: We recorded demographic information, hospitalization
      information, and eye examination information, including reason for consultation,
      type of consultation (screening examination, new eye problem, or preexisting eye
      problem), as well as primary and secondary ophthalmologic diagnoses. RESULTS:
      Internal medicine services requested 39.7% of consultations, surgery services
      20.9%, and trauma services 13.5%. There were 92 different reasons why
      consultations were requested. The most common reason was decreased vision. Eye
      problems that developed either on the day of admission or some time during
      hospitalization accounted for 39.6% of consultations, preexisting eye problems
      accounted for 31.6%, and screening examinations for the remaining 28.7%. We
      recorded 166 unique primary ophthalmologic diagnoses and 130 unique secondary
      ophthalmologic diagnoses. The top five common primary ophthalmologic diagnoses
      were refractive error (88 patients), fungal endophthalmitis ruled out (80
      patients), conjunctivitis (56 patients), diabetic retinopathy (52 patients), and
      corneal abrasion (52 patients). Refractive error was the most common secondary
      ophthalmologic diagnosis (201 patients). Inpatient diagnostic or surgical
      procedures were performed 7911 times. There were 947 unique primary and 1391
      unique secondary hospital discharge diagnoses. The most common primary discharge
      diagnosis, human immunodeficiency virus infection, accounted for only 1.6% of all
      hospitalizations, indicating a considerable diversity of systemic disease in the
      study population. CONCLUSIONS: This study profiled the typical patients and eye
      problems an ophthalmologist may expect to encounter when inpatient consultation
      is requested. The information may be useful for the planning and management of
      consultation services in residency training programs.

PMID- 11470712
TI  - Update on total parenteral nutrition.

PMID- 11470713
TI  - What does it mean to be "at nutritional risk"? Seeking clarity on behalf of the
      elderly.

PMID- 11470714
TI  - Prevalence of cobalamin (vitamin B-12) and folate deficiency in India--audi
      alteram partem.

PMID- 11470715
TI  - Total parenteral nutrition: potion or poison?
AB  - The role of nutritional support in clinical care has burgeoned over the past 40
      y. Initially, total parenteral nutri-tion (TPN) was considered to be the standard
      of care. Later, the concept that enteral nutrition (EN) promoted gut function and
      prevented the translocation of intestinal bacteria resulted in EN becoming the
      standard of care. Furthermore, TPN was consid-ered to be a dangerous form of
      therapy. Critical review of the data suggests that, in humans, TPN does not cause
      mucosal atrophy or increase bacterial translocation. Increased sepsis with TPN
      can be ascribed to overfeeding; the dangers of TPN-induced complications have
      been exaggerated. TPN is an equally effective alternative to EN when a risk of
      malnutrition is present and EN is not tolerated or when gut failure is present.

PMID- 11470716
TI  - Translation of nutritional sciences into medical education: the Nutrition
      Academic Award Program.
AB  - For the past 40 y the scientific community has decried the inadequacy of the
      training of physicians and other health professionals in the subject of human
      nutrition. In 1997 the National Heart, Lung, and Blood Institute developed the
      Nutrition Academic Award (NAA) Program, an initiative to improve nutrition
      training across a network of US medical schools. The purpose of this funding,
      which began in 1998, is to support the development and enhancement of nutrition
      curricula for medical students, residents, and practicing physicians to learn
      principles and practice skills in nutrition. The NAA recipients developed the
      Nutrition Curricular Guide for Training Physicians, a plan to incorporate
      clinical guidelines into physician practice skills, create educational and
      assessment practice tools, and evaluate curricula, materials, and teaching tools.
      Dissemination of NAA activities and materials will be facilitated by a national
      website, presentations and publications, and consultants and advisors from the
      NAA nutrition education programs. The NAA Program constitutes a major new effort
      to enhance nutrition knowledge and skills among health care providers and to
      effectively apply the science of human nutrition to clinical medicine. This
      article describes the purpose and aims of the NAA Program, the organizational
      structure of the network of recipients, a profile of the recipients and
      individual programs at 21 medical schools, the various strategies to overcome
      barriers in training physicians in human nutrition, and collaborative and
      dissemination efforts.

PMID- 11470717
TI  - Effects of different nutrient intakes on daytime triacylglycerolemia in healthy,
      normolipemic, free-living men.
AB  - BACKGROUND: Postprandial studies with standardized mixed meals have shown that
      ingestion of high-carbohydrate diets is associated with elevated plasma
      triacylglycerol (TG) concentrations. OBJECTIVE: We evaluated the effects of
      different nutritional components on daytime triacylglycerolemia in 58 healthy,
      free-living, normolipemic men. DESIGN: Capillary TG (TGc) was self-measured at 6
      fixed time points over 3 d. Daytime TGc profiles were calculated as areas under
      the curve (AUCs) for absolute and incremental changes in TGc concentrations (TGc
      AUC and DeltaTGc-AUC, respectively). Food intake was recorded in a diary.
      RESULTS: The mean (+/-SD) fasting TGc concentration, TGc-AUC, and DeltaTGc-AUC
      were 1.20 +/- 0.41 mmol/L, 24.1 +/- 6.9 mmol x h/L, and 7.3 +/- 4.5 mmol x h/L,
      respectively. Mean total energy intake was 10881 +/- 2536 kJ/d. Total intakes of
      fat, carbohydrate, and protein were 95 +/- 25 (33% of energy), 304 +/- 69 (48% of
      energy), and 101 +/- 27 (16% of energy) g/d, respectively. Fasting TGc
      concentrations and TGc-AUC were not related to dietary intake. The mean DeltaTGc
      AUC was significantly related to total carbohydrate (r = 0.38, P < 0.005),
      protein (r = 0.29, P < 0.05), and energy (r = 0.28, P < 0.05) intakes. Fat intake
      (as a % of energy) was negatively associated with the mean DeltaTGc-AUC (r = 
      0.30, P < 0.05). When the study group was subdivided into tertiles on the basis
      of fat intake (27.2%, 33.5%, and 39.1% of energy, respectively), carbohydrate
      intake was 50.9%, 48.1%, and 44.6% of energy, respectively. DeltaTGc-AUC was
      significantly lower at the highest tertile of fat intake (4.8 +/- 4.3 mmol x h/L)
      than at the lowest (8.2 +/- 4.0 mmol x h/L) and intermediate (8.9 +/- 4.3 mmol x
      h/L) tertiles (P < 0.05 for each). CONCLUSION: DeltaTGc-AUC is associated with
      the carbohydrate content of the diet in free-living men.

PMID- 11470718
TI  - Pork with a high content of polyunsaturated fatty acids lowers LDL cholesterol in
      women.
AB  - BACKGROUND: Animal products contribute significantly to the saturated fat and
      cholesterol content of the American diet. Contrary to dietary advice, consumers
      have not limited their consumption of animal products. Thus, an alternative
      approach might be to modify the fatty acid composition of animal products.
      OBJECTIVE: We tested the hypothesis that modified pork with a high content of
      polyunsaturated fatty acids (PUFAs) and a low content of saturated fatty acids
      (SFAs) would lower plasma LDL-cholesterol concentrations in women. DESIGN: Twenty
      women aged 19-24 y completed a crossover study with 2 diets. Nutritionally
      complete diets containing 42% of energy from fat differed only in the inclusion
      of either standard or modified pork. Venous blood samples were collected at weeks
      0, 4, and 8. RESULTS: The diet containing modified pork significantly lowered
      total plasma (P < 0.0076) and LDL (P < 0.0382) cholesterol. The modified diet
      also resulted in an increase in the PUFA and a decrease in the SFA and
      monounsaturated fatty acid contents of the cholesteryl ester, free fatty acid,
      phospholipid, and triacylglycerol lipid classes in both plasma and erythrocytes.
      Plasma concentrations of glucose, insulin, triacylglycerol, and free fatty acids
      did not change significantly. CONCLUSIONS: Consumption of pork with a high PUFA
      content resulted in a decrease in the subjects' total plasma and LDL cholesterol
      and shifted the fatty acid composition from SFAs to PUFAs in the plasma and
      erythrocytes. Modification of the fatty acid composition of animal foods will be
      a useful approach to lowering the saturated fat consumption of Americans.

PMID- 11470719
TI  - Use of biological markers to validate self-reported dietary intake in a random
      sample of the European Prospective Investigation into Cancer United Kingdom
      Norfolk cohort.
AB  - BACKGROUND: The validity of dietary assessment methods should be established
      before diet-disease associations are reported. OBJECTIVE: Our objective was to
      validate a 7-d food diary and a food-frequency questionnaire (FFQ) against
      independent biomarkers of intake in urine (nitrogen, potassium, and sodium) and
      blood (plasma ascorbic acid). DESIGN: A total of 146 healthy middle-aged men and
      women were recruited from the European Prospective Investigation into Cancer UK
      Norfolk cohort, a free-living cohort of approximately 25000 persons. Over a 9-mo
      period, urinary nitrogen, potassium, and sodium were estimated from 2-6 complete
      24-h urine collections in 134 subjects and plasma ascorbic acid was estimated
      from 2-3 fasting blood samples in 118 subjects. Subjects completed 2 FFQs and two
      7-d food diaries. RESULTS: In men and women combined, correlations between 24-h
      urinary nitrogen excretion and dietary intake from the 7-d food diary were high
      (r = 0.57-0.67) compared with those for the FFQ (r = 0.21-0.29). Similarly,
      correlations between urinary potassium and dietary potassium were higher for the
      7-d food diary (r = 0.51-0.55) than for the FFQ (r = 0.32-0.34). There was no
      overall difference in correlations between plasma ascorbic acid and dietary
      vitamin C between the 7-d food diary (r = 0.40-0.52) and the FFQ (r = 0.44-0.45).
      CONCLUSIONS: These data indicate that, despite increased subject burden, the 7-d
      food diary provided a better estimate of nitrogen and potassium intakes than did
      the FFQ in this study population. However, with respect to plasma ascorbic acid,
      both the FFQ and 7-d food diary provided a similar ranking of subjects according
      to vitamin C intake.

PMID- 11470720
TI  - Cognitive restraint can be offset by distraction, leading to increased meal
      intake in women.
AB  - BACKGROUND: Cognitive restraint, a stable disposition to limit food intake, can
      be assessed by questionnaires, but there is no quantitative, objective measure of
      its effect. OBJECTIVE: The goal was to provide an objective measure of the intake
      limiting effects of cognitive restraint by testing meal intake under conditions
      intended to minimize or accentuate restraint. DESIGN: Healthy women (n = 41; aged
      35 +/- 9 y; body mass index, in kg/m2: 21.3 +/- 1.9) participated in once-weekly
      laboratory lunch tests under 4 conditions: condition 1, subjects ate alone
      (baseline); condition 2, subjects ate alone while listening to recorded
      instructions focusing on the sensory characteristics of the foods (attention);
      condition 3, subjects ate alone while listening to a recorded detective story
      (distraction); and condition 4, a group of 4 subjects had lunch together. On all
      occasions, the same foods were presented and ingested ad libitum. The Three
      Factor Eating Questionnaire (TFEQ) was filled out after the series of 4 meals was
      completed. RESULTS: Meal size was significantly higher in the distraction
      condition than at baseline (by 301 +/- 26 kJ; P < 0.001). The difference in
      energy intake between the baseline and distraction conditions significantly
      correlated with factor 1 (cognitive restraint) of the TFEQ (r = 0.51, P < 0.01)
      and with total score (r = 0.32, P < 0.05) but not with disinhibition or hunger.
      For each additional point on factor 1, meal size increased by 50 kJ under the
      distraction condition compared with baseline. The group eating condition induced
      no increase in meal size. CONCLUSION: Cognitive restraint exerts a quantifiable
      limiting effect on intake at meal times and this effect can be offset by
      cognitive distraction.

PMID- 11470721
TI  - Screening for hospitalization and nutritional risks among community-dwelling
      older persons.
AB  - BACKGROUND: The potential for the use of nutritional screening to identify older
      persons at risk of hospitalization has not been contrasted with the use of tools
      developed for predicting hospital admissions. OBJECTIVE: Our goal was to compare
      the associations of items from the Level II Nutrition Screen (LII) and the
      Probability of Repeated Admissions (P(ra)) questionnaire with the outcome of
      hospitalization. DESIGN: This was a cohort study of participants in a Medicare
      managed-risk health plan who completed both the LII and P(ra) (n = 386). All
      hospitalizations within 1 y of screening were recorded. Hierarchical multivariate
      logistic regression was used to model associations with hospitalization. RESULTS:
      P(ra) items that retained significant associations with hospitalization were self
      reported health, hospitalization in the past year, and >6 doctor visits in the
      past year (positive predictive value: 20%; sensitivity: 53.1; specificity: 69.7).
      LII items that retained significant associations with hospitalization were eating
      problems and polypharmacy (positive predictive value: 17.9%; sensitivity: 58.0;
      specificity: 56.3). Those persons designated by the P(ra) score as being at high
      risk of hospitalization (P(ra) > or = 0.30, 75th percentile) were also more
      likely to report weight loss, polypharmacy, consumption of a special diet, and
      functional limitation on the LII. CONCLUSIONS: Retained items from the P(ra) and
      the LII were comparable in identifying participants at risk of hospitalization.
      These observations suggest that nutritional risk factors such as eating problems,
      weight loss, and consumption of special diets should be considered in the
      management of older persons at risk of hospitalization, irrespective of the
      screening approach selected.

PMID- 11470722
TI  - Vitamin D status affects serum parathyroid hormone concentrations during winter
      in female adolescents: associations with forearm bone mineral density.
AB  - BACKGROUND: Vitamin D deficiency leads to secondary hyperparathyroidism, which
      has a negative effect on bone metabolism in the elderly. Puberty is an important
      time of bone metabolism and growth. The effect of serum 25-hydroxyvitamin D
      [25(OH)D] concentrations on parathyroid hormone concentrations and bone mineral
      density (BMD) has not been well studied cross-sectionally in adolescents.
      OBJECTIVE: We studied the effect of vitamin D status on serum intact parathyroid
      hormone (iPTH) concentrations and bone metabolism in adolescents. DESIGN: One
      hundred seventy-eight healthy female adolescents (aged 14-16 y) volunteered for
      this study, which was conducted in Finland (Helsinki, 60 degrees N) during the
      winter. Forearm BMD at radial and ulnar sites was measured by dual energy X-ray
      absorptiometry. The determinants of different variables were studied by use of
      regression models. RESULTS: On the basis of the relation between serum 25(OH)D
      and iPTH concentrations, serum 25(OH)D concentrations > approximately 40 nmol/L
      were needed to keep serum iPTH concentrations low. One hundred ten subjects
      (61.8%) had serum 25(OH)D concentrations < or =40 nmol/L. Twenty-four subjects
      (13.5%) were considered vitamin D deficient when the serum 25(OH)D concentration
      of 25 nmol/L was used as a cutoff. Subjects with serum 25(OH)D concentrations <
      or =40 nmol/L had low mean forearm BMD values at both the radial (P = 0.04) and
      ulnar (P = 0.08) sites. CONCLUSION: A large percentage of adolescent females have
      low vitamin D status during the winter in Finland, which seems to have negative
      effects on bone health.

PMID- 11470723
TI  - Vitamin E in fortified cow milk uniquely enriches human plasma lipoproteins.
AB  - BACKGROUND: Milk fat may contribute to atherogenesis in humans. OBJECTIVE: We
      sought to offset the atherogenic potential of milk fat by adding polyunsaturated
      fat and vitamin E to milk. DESIGN: We measured plasma lipids, lipoproteins, and
      tocopherol and LDL oxidation in normolipemic adults. In experiment 1 (n = 48), we
      compared delivery of 100 mg all-rac-alpha-tocopheryl acetate/d in capsules, skim
      milk, and 1%-fat milks containing soybean oil, milk fat, or both (1:1). In
      experiment 2 (n = 24), we compared delivery of natural (RRR-alpha-tocopheryl
      acetate) and synthetic (all-rac-alpha-tocopheryl acetate) vitamin E in milk with
      delivery of all-rac-alpha-tocopheryl acetate in orange juice (200 mg/d in each
      group). In experiment 3 (n = 7), we compared delivery of 30 mg all-rac-alpha
      tocopheryl acetate/d in milks with and without added vitamins A and D. RESULTS:
      Enrichment of milk fat with soybean oil did not alter plasma lipoproteins.
      Microdispersion of vitamin E in milks increased the molar ratio of plasma
      tocopherol to cholesterol by >2-fold compared with the molar ratio after
      consuming vitamin E capsules, whereas the molar ratios were comparable after
      ingestion of orange juice and capsules. Synthetic and natural vitamin E performed
      comparably. The enhanced plasma vitamin E:cholesterol attributed to milk
      increased protection of LDL against oxidation. Vitamins A and D did not affect
      vitamin E delivery by milk. CONCLUSIONS: Milk augments vitamin E transport by
      human lipoproteins at intakes of 100-200 but not 30 mg/d. This augmentation is
      independent of the presence and type of fat in milk, its vitamin A and D
      contents, and whether the vitamin E is natural or synthetic.

PMID- 11470724
TI  - Aspirin intake and the use of serum ferritin as a measure of iron status.
AB  - BACKGROUND: Atherosclerosis, a primary cause of myocardial infarction (MI), is an
      inflammatory disease. Aspirin use lowers risk of MI, probably through
      antithrombotic and antiinflammatory effects. Because serum ferritin (SF) can be
      elevated spuriously by inflammation, reported associations between elevated SF,
      used as an indicator of iron stores, and heart disease could be confounded by
      occult inflammation and aspirin use if they affect SF independently of iron
      status. OBJECTIVE: We tested the hypothesis that aspirin use is associated with
      reduced SF. DESIGN: We used analysis of covariance to investigate the relation
      between SF and categories of aspirin use in 913 elderly participants aged 67-96 y
      in the Framingham Heart Study. RESULTS: After adjustment for sex, age, body mass
      index, smoking, alcohol use, concentrations of C-reactive protein and liver
      enzymes, white blood cell count, and use of nonaspirin nonsteroidal
      antiinflammatory drugs and other medications, subjects who took >7 aspirins/wk
      had a significantly lower (by 25%) geometric mean SF than did nonusers, who took
      <1 aspirin/wk (71 compared with 95 microg/L, respectively; P for trend = 0.004).
      This effect of aspirin on SF was more marked in diseased subjects than in healthy
      subjects (mean SF was 50% lower compared with 21% lower, respectively).
      CONCLUSIONS: Aspirin use is associated with lower SF. We suggest this effect
      results from possible increased occult blood loss and a cytokine-mediated effect
      on SF in subjects with inflammation, infection, or liver disease. The relations
      between aspirin, inflammation, and SF may confound epidemiologic associations
      between elevated SF, as an indicator of iron stores, and heart disease risk.

PMID- 11470725
TI  - Catechin intake might explain the inverse relation between tea consumption and
      ischemic heart disease: the Zutphen Elderly Study.
AB  - BACKGROUND: Epidemiologic studies suggest that tea consumption may reduce the
      risk of cardiovascular diseases, but results are inconsistent. Catechins, which
      belong to the flavonoid family, are the main components of tea and may be
      responsible for the alleged protective effect. Taking catechin sources other than
      tea into account might clarify the reported associations. OBJECTIVE: The
      objective was to evaluate the association between catechin intake and the
      incidence of and mortality from ischemic heart disease and stroke. DESIGN: We
      evaluated the effect of a high catechin intake by using data from the Zutphen
      Elderly Study, a prospective cohort study of 806 men aged 65-84 y at baseline in
      1985. RESULTS: The mean (+/-SD) catechin intake at baseline was 72 +/- 47.8 mg,
      mainly from black tea, apples, and chocolate. A total of 90 deaths from ischemic
      heart disease were documented. Catechin intake was inversely associated with
      ischemic heart disease mortality; the multivariate-adjusted risk ratio in the
      highest tertile of intake was 0.49 (95% CI: 0.27, 0.88; P for trend: 0.017).
      After multivariate adjustment, catechin intake was not associated with the
      incidence of myocardial infarction (risk ratio in the highest tertile of intake:
      0.70; 95% CI: 0.39, 1.26; P for trend: 0.232). After adjustment for tea
      consumption and flavonol intake, a 7.5-mg increase in catechin intake from
      sources other than tea was associated with a tendency for a 20% reduction in
      ischemic heart disease mortality risk (P = 0.114). There was no association
      between catechin intake and stroke incidence or mortality. CONCLUSION: Catechins,
      whether from tea or other sources, may reduce the risk of ischemic heart disease
      mortality but not of stroke.

PMID- 11470726
TI  - Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence
      of cobalamin deficiency in Asian Indians.
AB  - BACKGROUND: In India, most people adhere to a vegetarian diet, which may lead to
      cobalamin deficiency. OBJECTIVE: The objective was to examine indicators of
      cobalamin status in Asian Indians. DESIGN: The study population included 204 men
      and women aged 27-55 y from Pune, Maharashtra, India, categorized into 4 groups:
      patients with cardiovascular disease (CVD) and diabetes, patients with CVD but no
      diabetes, patients with diabetes but no CVD, and healthy subjects. Data on
      medical history, lifestyle, and diet were obtained by interviews and
      questionnaires. Blood samples were collected for measurement of serum or plasma
      total cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total
      homocysteine (tHcy) and hemetologic indexes. RESULTS: MMA, tHcy, total cobalamin,
      and holoTC did not differ significantly among the 4 groups; therefore, the data
      were pooled. Total cobalamin showed a strong inverse correlation with tHcy (r = 
      0.59) and MMA (r = -0.54). Forty-seven percent of the subjects had cobalamin
      deficiency (total cobalamin <150 pmol/L), 73% had low holoTC (<35 pmol/L), 77%
      had hyperhomocysteinemia (tHcy >15 micromol/L), and 73% had elevated serum MMA
      (>0.26 micromol/L). These indicators of impaired cobalamin status were observed
      in both vegetarians and nonvegetarians. Folate deficiency was rare and only 2.5%
      of the subjects were homozygous for the MTHFR 677C-->T polymorphism. CONCLUSIONS:
      About 75% of the subjects had metabolic signs of cobalamin deficiency, which was
      only partly explained by the vegetarian diet. If impaired cobalamin status is
      confirmed in other parts of India, it may have important health implications.

PMID- 11470727
TI  - Contribution of dietary and newly formed arachidonic acid to human milk lipids in
      women eating a low-fat diet.
AB  - BACKGROUND: Polyunsaturated fatty acids in milk are derived from direct
      intestinal absorption, endogenous synthesis, or maternal body stores. Arachidonic
      acid (AA) intake is frequently low in undernourished women, but milk secretion of
      this fatty acid is similar to that in well-nourished women. OBJECTIVE: The
      objective was to evaluate the contribution of dietary and endogenously
      synthesized AA to its total secretion in the milk of women eating a low-fat diet.
      DESIGN: Ten lactating women who habitually ate a low-fat diet (17% of energy)
      received 2.5 mg [(13)C]linoleic acid (LA)/kg body wt orally 5 mo postpartum. LA
      and AA concentrations and (13)C enrichment were measured in milk samples
      collected before and after the tracer application. Total lipid, LA, and AA
      contents were determined in diet composites. Fatty acids were assessed by gas
      chromatography and (13)C enrichment by isotope ratio mass spectrometry. RESULTS:
      The cumulative 72-h recovery of [(13)C]LA in milk was 16.3 +/- 6.4% of the dose;
      only 0.01% of the label was found as [(13)C]AA. The calculated transfer of
      dietary LA and AA into milk was 32.8 +/- 18.0% and 11.8 +/- 6.6%, respectively.
      AA originating from conversion of dietary LA contributed only 1.1% to the total
      milk AA secreted. CONCLUSIONS: Little milk AA originates from conversion of LA;
      70% of LA and 90% of AA secreted in milk were not derived from direct intestinal
      absorption. Our results suggest that maternal body stores are the major source of
      milk LA and AA in these women.

PMID- 11470728
TI  - The National Center for Health Statistics reference and the growth of Indian
      adolescent boys.
AB  - BACKGROUND: Few studies describing the growth of adolescents exist because of the
      difficulties in interpreting anthropometric data in this age group. OBJECTIVE: We
      describe the growth of adolescent boys from West Bengal, India, and assess the
      adequacy of using the National Center for Health Statistics (NCHS) reference
      data. DESIGN: A cross-sectional anthropometric survey was conducted in 818
      Bengali boys from middle-class families. Anthropometric measurements were taken
      on each subject's birthday (+/-3 d) by use of standard measuring techniques. The
      NCHS reference data on height and body mass index (BMI) were used to estimate age
      specific prevalences of stunting, thinness, and overweight. BMI was also assessed
      by using British, Dutch, and French reference data. The biological parameters of
      the adolescent growth spurt were estimated by using the Preece-Baines growth
      model. RESULTS: With use of the 5th percentile of the NCHS reference data, the
      prevalence of thinness was approximately 5 times (50.5%) that of stunting
      (11.2%). The median curves of the 3 European references lay between the Indian
      and NCHS samples and also yielded high prevalences of thinness when applied to
      the study sample. The prevalence of being at risk of overweight was low (4.2%).
      Mean age at peak height velocity was 13.0 y and peak height velocity was 7.0
      cm/y. CONCLUSIONS: The NCHS reference data seem inadequate for this sample.
      Consideration should be given to developing appropriate reference data based on
      healthy adolescent populations from different ethnic groups. Issues of maturation
      related variation in assessing growth during adolescence should be given
      particular attention.

PMID- 11470729
TI  - Measurements of the gastric emptying rate by use of ultrasonography: studies in
      humans using bread with added sodium propionate.
AB  - BACKGROUND: Foods with a low glycemic index are increasingly being acknowledged
      as beneficial for individuals with disorders related to the insulin resistance
      syndrome. The presence of certain salts of organic acids has been shown to lower
      the glycemic index of bread products and one of the suggested mechanisms is a
      lowered gastric emptying rate (GER). One obvious pitfall with many of the common
      techniques for GER measurement is that the food structure, and hence the gastric
      release of nutrients, may be affected by enclosure of the marker for gastric
      emptying, eg, paracetamol. Ultrasonography is a noninvasive method for which the
      above pitfall is to a large extent avoided. OBJECTIVE: The main objective was to
      evaluate the use of ultrasonography to determine whether the lowered glycemic and
      insulinemic responses to bread ingestion after the addition of sodium propionate
      are explained by a specific effect of propionate on the GER. DESIGN: The effect
      of sodium propionate in bread was evaluated in 9 healthy volunteers. Barley bread
      products, with or without added sodium propionate, were ingested as breakfast
      after an overnight fast. The GER was monitored for 2 h by ultrasonography; during
      this period, capillary blood was withdrawn repeatedly for measurement of blood
      glucose and insulin. RESULTS: The GER of the barley bread decreased markedly
      after the addition of sodium propionate and was accompanied by lowered glycemic
      and insulinemic responses. CONCLUSION: The lowered glycemic response to ingestion
      of bread with added sodium propionate appears to be related to a lowered GER.

PMID- 11470730
TI  - Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease.
AB  - BACKGROUND: In Crohn disease (CD), the increased production of reactive oxygen
      species from activated neutrophils may reduce plasma concentrations of
      antioxidant vitamins and result in increased oxidative stress. OBJECTIVE: We
      compared lipid peroxidation, a measure of reactive-oxygen-species production, and
      plasma antioxidant vitamin concentrations between CD patients and healthy control
      subjects. DESIGN: Thirty-seven nonsmoking CD patients (22 women and 15 men) were
      compared with an equal number of healthy control subjects who were matched by
      age, sex, and body mass index. In patients the mean CD activity index (CDAI) was
      141.2 +/- 18.7 (range: 9.0-514), and 11 of 37 patients (30%) had a CDAI > or
      =150. Seventy-eight percent of patients were taking > or = 1 medication.
      Medication use by subjects included the following: 5-aminosalicylic acid (40% of
      subjects), antibiotics (22%), oral corticosteroids (30%), and immunosuppressants
      (19%). RESULTS: Lipid peroxidation as measured by breath pentane output (CD
      patients, 7.47 +/- 0.98 pmol x kg(-1) x min(-1); control subjects, 4.97 +/- 0.48
      pmol x kg(-1) x min(-1); P < or = 0.025), breath ethane output (CD patients,
      11.24 +/- 1.17 pmol x kg(-1) x min(-1); control subjects, 5.46 +/- 0.71 pmol x
      kg(-1) x min(-1); P < or = 0.0005) and F2-isoprostane (CD patients, 78.6 +/- 8.0
      ng/L; control subjects, 60.6 +/- 3.7 ng/L; P < or = 0.047) were significantly
      higher in CD patients than in control subjects. Plasma antioxidant vitamins
      (ascorbic acid, alpha- and beta-carotene, lycopene, and beta-cryptoxanthin) were
      all significantly lower in CD patients than in control subjects. There were no
      significant differences in macro- and micronutrient intakes between groups.
      CONCLUSION: Patients with CD are oxidatively stressed, which was observed even
      though 70% of patients had a CDAI < or =150 and 78% of them were taking
      medications to treat CD.

PMID- 11470731
TI  - Similar metabolic responses to standardized total parenteral nutrition of septic
      and nonseptic critically ill patients.
AB  - BACKGROUND: Nutritional support is an important link between the response to
      injury and recovery in critical illness. OBJECTIVE: Our goal was to evaluate
      energy and substrate metabolism in septic and nonseptic critically ill patients
      in the resting state and during the administration of standardized total
      parenteral nutrition. DESIGN: This was a prospective, clinical cohort study of 25
      consecutively admitted critically ill patients either with (n = 14) or without (n
      = 11) sepsis who received total parenteral nutrition. Resting energy expenditure
      was measured on days 0, 2, and 7 by indirect calorimetry. Energy and substrate
      balances were calculated on days 2 and 7. RESULTS: Resting energy expenditure was
      not significantly different between septic and nonseptic patients on day 0 (2.65
      +/- 0.49 and 2.36 +/- 0.56 kJ x min(-1) x m(-2), respectively). Energy balances
      were positive for both groups on days 2 (0.68 +/- 0.4 and 0.74 +/- 0.6 kJ x min(
      1) x m(-2), respectively; NS) and 7 (0.65 +/- 0.3 and 0.78 +/- 0.5 kJ x min(-1) x
      m(-2), respectively; NS). Substrate balances were not significantly different
      between groups on days 0, 2, and 7. Resting energy expenditure on day 0 was
      negatively correlated with the severity of illness in septic patients only (r = 
      0.58, P < 0.05). CONCLUSIONS: Metabolic changes were not significantly different
      between septic and nonseptic critically ill patients during the administration of
      standardized total parenteral nutrition. A disease-specific macronutrient
      composition of total parenteral nutrition formulas does not seem to be necessary
      in either septic or nonseptic critically ill patients.

PMID- 11470733
TI  - Mild hyperhomocysteinemia: vitamin supplementation or not?

PMID- 11470735
TI  - Fat emulsion infusions and prolongation of the Q-T interval.

PMID- 11470737
TI  - Validity of dietary assessment.

PMID- 11470738
TI  - A reappraisal of the potential chemopreventive and chemotherapeutic properties of
      resveratrol.
AB  - Resveratrol, a phytoalexin found in grapes and wines, has been reported to
      exhibit a wide range of pharmacological properties and is believed to play a role
      in the prevention of human cardiovascular disease (the so-called 'French
      paradox'). This molecule may also play a major role in both cancer prevention and
      therapy. In this review article we summarize the recent advances that have
      provided new insights into the molecular mechanisms underlying the promising
      properties of resveratrol. These include cyclooxygenase, nitric oxide synthase
      and cytochrome P450 inhibition, as well as cell cycle effects, apoptosis
      modulation and hormonal activity.

PMID- 11470739
TI  - Esophageal adenocarcinoma: a review and perspectives on the mechanism of
      carcinogenesis and chemoprevention.
AB  - The incidence rate of esophageal adenocarcinoma (EAC) has increased sharply in
      the past 30 years. Many risk factors have been identified and gastroesophageal
      reflux disease (GERD) is the most important one. Columnar-lined esophagus,
      resulting from GERD, is recognized as a key precursor lesion of EAC. In this
      article, we review the studies on EAC in humans and animal models. We propose
      that the pathogenesis of EAC is mainly driven by inflammation and oxidative
      stress, which are augmented by iron overload. The overproduction of prostaglandin
      E2 and leukotriene B4 and overexpression of their receptors are believed to be
      major factors in exacerbating inflammation and oxidative stress. Based on this
      mechanistic understanding, antioxidants, inhibitors of arachidonic acid
      metabolism enzymes and receptor antagonists of certain eicosanoids are proposed
      as potential chemopreventive agents for EAC in future studies.

PMID- 11470740
TI  - hMSH3 overexpression and cellular response to cytotoxic anticancer agents.
AB  - Mutations or transcriptional silencing of mismatch repair genes have been linked
      with tumour cell resistance to O(6)-guanine methylating agents, 6-thioguanine,
      cisplatin, doxorubicin and etoposide. Recently, it has been demonstrated that
      overexpression of the MSH3 protein is associated with depletion of the mismatch
      binding factor MutSalpha, and then with a marked reduction in the efficiency of
      base/base mismatch repair. In the present study we evaluated sensitivity of the
      HL-60 cell line and its methotrexate-resistant subline HL-60R, which
      overexpresses the hMSH3 gene, to a panel of chemotherapeutic agents. Cell growth
      inhibition induced by temozolomide, 6-thioguanine and N-methyl-N'-nitro-N
      nitrosoguanidine was significantly lower in the hMSH3-overexpressing HL-60R cell
      line as compared with the HL-60 parental line. Moreover, HL-60R cells were more
      resistant than HL-60 cells to chromosome aberrations induced by either N-methyl
      N'-nitro-N-nitrosoguanidine or temozolomide, and to apoptosis triggered by the
      latter drug. Both cell lines were equally susceptible to growth inhibition
      induced by cisplatin, etoposide or doxorubicin. In addition, HL-60 and HL-60R
      cells showed comparable sensitivity to the clastogenic and apoptotic effects of
      cisplatin and etoposide. These results further confirm that loss of base/base
      mismatch repair is the most important molecular mechanism involved in cell
      resistance to O(6)-guanine methylating agents and 6-thioguanine. However, the
      status of the mismatch repair system could still influence tumour cell
      sensitivity to cisplatin, etoposide and doxorubicin, depending on the specific
      component of the system that is lost, and on the genetic background of the cell.

PMID- 11470741
TI  - Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways
      involved in the invasiveness and metastatic properties of highly invasive breast
      cancer cell lines: an in vitro study.
AB  - Cerivastatin is used in the treatment of hypercholesterolemia to inhibit 3
      hydroxy 3-methylglutaryl coenzyme A reductase and thus prevent the synthesis of
      cholesterol precursors, such as farnesyl pyrophosphate (FPP) and geranylgeranyl
      pyrophosphate (GGPP), responsible, respectively, for translocation of Ras and Rho
      to the cell membrane, a step required for their cell signaling, leading to cell
      proliferation and migration. Recently, it has been suggested that non lipid
      related effects of statins could play a beneficial role in cancer therapy. In
      this study, we have investigated the mechanisms by which statins inhibit cancer
      and the types of cancers which could benefit from this therapy. In MDA-MB-231
      cells, an aggressive breast cancer cell line with spontaneous activation of Ras
      and NFkappaB and overexpression of RhoA, cerivastatin induced inhibition of both
      cell proliferation and invasion through Matrigel. This anti-proliferative effect
      was related to G(1)/S arrest due to an increase in p21(Waf1/Cip1). The anti
      invasive effect was observed from 18 h and could be explained by RhoA
      delocalization from the cell membrane, resulting in disorganization of the actin
      fibers and disappearance of focal adhesion sites. The importance of RhoA
      inactivation in both these inhibitory effects was proved by their reversion by
      GGPP but not by FPP. Moreover, cerivastatin was also shown to induce inactivation
      of NFkappaB, in a RhoA inhibition-dependent manner, resulting in a decrease in
      urokinase and metalloproteinase-9 expression, two proteases involved in cell
      migration. The participation of Ras inactivation is considered a subsidiary
      mechanism for the effects of cerivastatin, as they were not rescued by FPP.
      Prolonged treatment of MDA-MB-231 cells with high doses of cerivastatin induced a
      loss of cell attachment. Interestingly, the effect of cerivastatin was
      considerably lower on poorly invasive MCF-7 cells. In conclusion, our results
      suggest that cerivastatin inhibits cell signaling pathways involved in the
      invasiveness and metastatic properties of highly invasive cancers.

PMID- 11470742
TI  - Aberrant expression of G(1)/S regulators is a frequent event in sporadic
      pituitary adenomas.
AB  - Components of the pRb/p16/cyclin D1/CDK4 pathway are frequent targets in numerous
      tumour types, including those of pituitary origin. However, previous studies of
      pituitary tumours have examined individual components of this pathway. Therefore,
      to determine their overall contribution we have simultaneously examined the
      immunohistochemical status of pRb, p16 and cyclin D1 and analysed the CDK4 gene
      for a characterized activating mutation. Of the total pituitary tumour cohort (29
      clinically non-functioning adenomas and 16 somatotrophinomas) abnormal expression
      of either pRb, p16 or cyclin D1 was observed in 36 of 45 (80%) tumours and was
      significantly (P = 0.005) associated with non-functioning tumours (27/29; 93%)
      compared with somatotrophinomas (9/16, 56%). Loss of either pRb or p16 expression
      was mutually exclusive in 23 of 45 (51%) tumours, whilst concomitant loss of pRb
      and p16 expression was observed in five tumours. Cyclin D1 overexpression was
      observed in 22 of 45 (49%) tumours, however, there was no significant association
      between overexpression of cyclin D1 and the expression status of either pRb or
      p16. In addition, no activating mutations within codon 24 of the CDK4 gene were
      detected. This study provides evidence for the first time that components of the
      pRb/p16/cyclin D1/CDK4 pathway, either alone or in combination, are frequently
      deregulated in human pituitary tumours, suggesting that this pathway may be a
      useful target in drug or gene therapeutic approaches.

PMID- 11470743
TI  - Effects of the garlic compound diallyl disulfide on the metabolism, adherence and
      cell cycle of HT-29 colon carcinoma cells: evidence of sensitive and resistant
      sub-populations.
AB  - Diallyl disulfide (DADS) is a major organosulphur compound present in garlic with
      an anti-mitotic potential against colon neoplastic lesions in vivo and colon
      tumour cell growth in vitro. Using the human colon adenocarcinoma HT-29 Glc(-/+)
      cell line we identified sub-populations of tumoural cells with markedly different
      characteristics in terms of metabolic capacities, adhesion properties and
      distribution in the cell cycle phases. After 1 and 2 days treatment with 100
      microM DADS HT-29 cells were largely released into the culture medium. These
      floating cells accumulated in the G(2)/M phase and were characterized by a 5-fold
      reduction in cell capacity for de novo protein synthesis. Polyamine metabolism,
      which is necessary for intestinal epithelial cell attachment and growth, was also
      severely affected, since 3-fold reductions in polyamine biosynthesis and net
      accumulation of putrescine were measured after DADS treatment. However, oxidation
      of L-glutamine, the main precursor of the tricarboxylic acid cycle in these
      cells, and de novo synthesis of glutathione, a tripeptide involved in tumoural
      cell chemoresistance, were not affected by DADS treatment. In contrast, the
      adherent sub-population of HT-29 cells, although partially accumulated in G(2)/M
      phase, were characterized by unaffected metabolic capacities when compared with
      control cells except for putrescine accumulation, which was transiently
      decreased, and L-glutamine oxidation, which was increased 2-fold. DADS-resistant
      cells selected within 5 days were then able to proliferate at a similar rate to
      control untreated cells. The DADS-induced changes in HT-29 metabolic capacities,
      adhesion properties and the cell cycle are discussed from a causal perspective.

PMID- 11470744
TI  - Abbreviated cell cycle progression induced by the serine/threonine protein
      phosphatase inhibitor okadaic acid at concentrations that promote neoplastic
      transformation.
AB  - We examined cell cycle-related effects of the phosphatase inhibitor okadaic acid
      (OA) in T51B rat liver epithelial cells under conditions chosen to mimic early
      stages of tumor promotion by this compound. Optimal transformation (colony
      formation in soft agar) was seen after prolonged culture of N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG)-initiated T51B cells in 7 nM OA. Paradoxically, T51B
      cells treated with 2-10 nM OA showed decreased, rather than increased,
      proliferation in response to epidermal growth factor (EGF), as measured by
      [3H]thymidine incorporation. Complete inhibition was observed within 24 h at 10
      nM OA. This response paralleled a loss of EGF-stimulated cdk2 kinase activity and
      an increase in association of the inhibitors p21 (cip-1) and p27 (kip-1) with
      cdk2. An increase in p53 phosphorylated on serine 15 accompanied the rise in p21
      (cip-1). Both phosphorylation of the retinoblastoma protein and induction of
      cyclin A by EGF were blocked in cells treated with OA, but there was an increase
      in cyclin E. Resting cells treated with OA alone also showed elevated cyclin E
      levels, together with reduced levels of the E2F regulator pRb2/p130. Taken
      together, these observations indicate transforming levels of okadaic acid elicit
      a G(1)-trapping effect by facilitating cell cycle progression to the G(1)/S
      checkpoint, where cells are trapped by mechanisms that include p21 (cip-1)
      mediated inhibition of cdk2. They support the premise that disruption of cellular
      processes regulating the transitions from G(0) to G(1) to S-phase is an important
      early step in tumor promotion by low levels of okadaic acid.

PMID- 11470745
TI  - Interactions of beta-carotene and cigarette smoke in human bronchial epithelial
      cells.
AB  - Results from recent intervention trials indicated that supplemental beta-carotene
      enhances lung cancer incidence and mortality among smokers. It was hypothesized
      that beta-carotene was exerting its deleterious effects through a prooxidant
      effect in the smoke-exposed lung. To test this hypothesis we examined the
      interactions of beta-carotene and cigarette smoke in transformed human bronchial
      epithelial cells. We studied the effects of beta-carotene supplementation on
      rates of gas phase smoke-induced lipid peroxidation, membrane damage and
      depletion of endogenous antioxidants in BEAS-2B cells. Gas phase cigarette smoke
      caused cellular beta-carotene levels to decrease over time. The oxidation of beta
      carotene by smoke generated various oxidation products, including 4-nitro-beta
      carotene, beta-apo-carotenals and beta-carotene epoxides. Peroxidation of
      membrane lipids by gas phase smoke progressed at a slower rate than did oxidation
      of beta-carotene and incorporation of beta-carotene into the cells did not
      enhance the overall rate of lipid peroxidation. Additionally, lactate
      dehydrogenase release during smoke exposure was also unaffected by the presence
      or absence of beta-carotene in cells. beta-Carotene incorporation in cells was
      not found to accelerate the rates of alpha-tocopherol and glutathione depletion
      by cigarette smoke. Our results indicate that beta-carotene is more sensitive
      than lipids to cigarette smoke oxidation, but that this preferential oxidation of
      beta-carotene does not lead to a prooxidant effect in human bronchial epithelial
      cells.

PMID- 11470746
TI  - DNA damage-related RNA expression to assess individual sensitivity to ionizing
      radiation.
AB  - Predictive markers of intrinsic radiosensitivity in healthy individuals are
      needed in monitoring their occupational or environmental radiation exposure and
      may predict a patient's response to radiotherapy. Ionizing radiation can induce a
      large spectrum of DNA lesions, but under optimal DNA repair conditions, the
      principal residual lesions of importance are misrepaired double-strand breaks.
      The micronucleus (MN) assay represents a useful test in measuring
      radiosensitivity since it reflects non-repaired DNA breaks at the time of cell
      division. Spontaneous and radiation-induced MN vary greatly between individuals,
      and little is known about the molecular mechanisms of this variability. DNA
      repair and apoptosis processes are involved in the cellular response to radiation
      induced DNA damage, and variation in gene expression related to these cellular
      pathways could be linked to individual radiosensitivity. In this study we
      analysed by real-time quantitative RT-PCR the basal expression of 12 genes
      involved both in DNA repair and apoptosis in a series of blood samples obtained
      from 32 healthy male donors. Relationships between basal RNA expressions and MN
      frequency and distribution per bi-nucleated cell were studied after ex vivo
      irradiation of total blood samples. Our results indicate that the variability of
      mRNA gene expression among the 32 subjects appears to be of the same magnitude or
      higher than that found for spontaneous or radiation-induced MN frequency and that
      RAD51 gene expression is negatively correlated with radiation-induced MN
      frequency.

PMID- 11470747
TI  - XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ.
AB  - Forty-four Finnish volunteers who were previously studied with regard to the
      repair rate of UV-specific cyclobutane pyrimidine dimers in the skin were
      genotyped for XPD polymorphisms at codons 312 (exon 10 G-->A, Asp-->Asn) and 751
      (exon 23 A-->C, Lys-->Gln). The repair rate was measured at 24 h for two
      different cyclobutane dimers. The data did not show consistent XPD genotype
      specific differences in DNA repair rates among all subjects. The combined exon 10
      AA and exon 23 CC genotype was associated with an approximately 50% depression of
      repair rate but this was of borderline statistical significance. However, the
      exon 23 C allele was associated with depressed repair among subjects aged 50
      years or older and the result was consistent with both dimers.

PMID- 11470748
TI  - Green tea catechins partially protect DNA from (.)OH radical-induced strand
      breaks and base damage through fast chemical repair of DNA radicals.
AB  - The catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin
      gallate (ECG) and (-)-epigallocatechin gallate (EGCG) are believed to be active
      constituents of green tea accounting for the reported chemoprevention of certain
      cancers. The molecular mechanisms by which the measured low concentrations (ca.
      micromolar) of catechins in humans can reduce the incidence of carcinogenesis is
      not clear. Using an in vitro plasmid DNA system and radiolytically generating
      reactive oxygen species (ROS) under constant scavenging conditions, we have shown
      that all four catechins, when present at low concentrations, ameliorate free
      radical damage sustained by DNA. A reduction in both prompt DNA single-strand
      breaks and residual damage to the DNA bases, detected by subsequent incubation
      with the DNA glycosylases formamidopyrimidine (FPG), endonuclease III (EndoIII)
      and 5' AP endonuclease exonuclease III (ExoIII), was observed. EGCG was found to
      be the most active of the catechins, with effects seen at micromolar
      concentrations. Combined fast-reaction chemistry studies support a mechanism of
      electron transfer (or H-atom transfer) from catechins to ROS-induced radical
      sites on the DNA. These results support an antioxidant role for catechins in
      their direct interaction with DNA radicals.

PMID- 11470749
TI  - Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck:
      a case-control study.
AB  - A G-->A polymorphism (G870A) in exon 4 of the cyclin D1 (CCND1) gene creates an
      alternative splice site in its mRNA, encoding a protein with an altered C
      terminal domain. It has been suggested that DNA damage in cells with the A allele
      bypasses the G(1)/S checkpoint of the cell cycle more easily than damage in cells
      without the A allele. Because CCND1 plays a critical role in cell cycle control
      and reduced DNA repair capacity is associated with an increased risk for squamous
      cell carcinoma of the head and neck (SCCHN), we hypothesize that this CCND1
      polymorphism modulates individual susceptibility to SCCHN. To test this
      hypothesis we evaluated the frequency of the polymorphism in a hospital-based
      case-control study of 233 newly diagnosed SCCHN patients and 248 non-cancer
      controls. The cases and controls were frequency matched by age (+/-5 years), sex
      and tobacco use. All subjects were non-Hispanic whites. We found that the A
      allele frequency was slightly higher in the cases (0.485) than in the controls
      (0.425), but the difference was borderline statistically significant (P = 0.064).
      The frequencies of the CCND1 AA, GA and GG genotypes were 23.6, 49.8 and 26.6%,
      respectively, in cases and 16.5, 52.5 and 31.5%, respectively, in controls.
      Multivariate logistic regression analysis adjusting for age (in years), sex,
      smoking and alcohol use was performed to calculate odds ratios (OR) and 95%
      confidence intervals (CI). Compared with the wild-type CCND1 GG, the CCND1 A G
      genotype was associated with a non-significantly increased risk (adjusted OR
      1.15, 95% CI 0.75-1.76), but the CCND1 AA genotype was associated with a
      significantly increased risk (adjusted OR 1.77, 95% CI 1.04-3.02) for SCCHN.
      Results from a trend test using a logistic regression model were statistically
      significant (P = 0.044). Among the cases the mean age of onset was 59.0, 56.8 and
      55.5 years for the GG, GA and AA genotypes, respectively. In the stratification
      analysis the CCND1 AA variant genotype was associated with a >3-fold increased
      risk in individuals who were </=50 years old (OR 3.18, 95% CI 1.19-8.46), females
      (3.57, 1.26-10.0), non-smokers (3.71, 1.37-10.1) and non-alcohol users (4.76,
      1.61-14.0). These results suggest that the CCND1 polymorphism is associated with
      early onset of SCCHN and contributes to susceptibility to SCCHN in this
      population.

PMID- 11470750
TI  - Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated
      cell growth and gene expression in LNCaP prostate cancer cells.
AB  - There is some epidemiological support for a protective influence of omega-3 fatty
      acids against prostate cancer. We wanted to explore whether omega-3
      polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA) can affect androgen receptor function in prostate
      cancer cells. Our study showed that both DHA and EPA inhibit androgen-stimulated
      cell growth. Androgenic induction of prostate-specific antigen (PSA) protein was
      repressed by DHA and EPA in a dose-dependent manner. The mRNA levels of five
      androgen up-regulated genes, PSA, ornithine decarboxylase, NKX 3.1, immunophilin
      fkbp 51 and Drg-1, were decreased with DHA treatment in the presence of
      androgens. Transfection experiments using a DNA vector containing androgen
      responsive elements demonstrated that both DHA and EPA could interfere with
      transactivation activities of the androgen receptor (AR). However, western blot
      analysis of AR protein showed that DHA and EPA treatments did not change AR
      expression levels. Interestingly, the proto-oncoprotein c-jun was increased by
      DHA treatment. A transient transfection found that forced expression of c-jun
      inhibited AR transactivation activity. Thus, this study found that the inhibitory
      effects of omega-3 polyunsaturated fatty acids on AR-mediated actions are due, at
      least in part, to an increase in c-jun protein.

PMID- 11470751
TI  - Nitroglycerin: a NO donor inhibits TPA-mediated tumor promotion in murine skin.
AB  - Nitroglycerin (GTN), a nitric oxide (NO) generating vasodilator has been used in
      the present study to assess the role of NO during tumor promotion in murine skin.
      Administration of GTN to 12-O tetradecanoyl phorbol 13-acetate (TPA)-treated mice
      resulted in a dose-dependent inhibition in the level of glutathione and the
      activity of antioxidant enzymes by approximately 16-40% of acetone-treated
      control. We also observed that GTN application led to a significant reduction in
      the ornithine decarboxylase (ODC) activity and decreased the rate of
      [3H]thymidine incorporation into epidermal DNA when compared with the acetone
      treated control (P < 0.001). Treatment of DMBA-initiated TPA-promoted mice with
      GTN increased the latency period, decreased the tumor incidence by 32% and there
      was a 2-fold decrease in tumor yield (tumor/mouse) as compared with the TPA
      (alone)-treated group by 20 weeks. From these data, it can be concluded that NO
      can abrogate the toxic and tumor promoting effects of TPA and GTN can be used as
      a chemopreventive agent to inhibit tumorigenesis in murine skin.

PMID- 11470752
TI  - Restoration of retinoic acid concentration suppresses ethanol-enhanced c-Jun
      expression and hepatocyte proliferation in rat liver.
AB  - Chronic and excessive ethanol intake decreases hepatic retinoic acid (RA)
      concentrations, which may play a critical role in ethanol-induced
      hyperproliferation in hepatocytes. The present study was conducted to determine
      whether RA supplementation in chronic ethanol-fed rats could restore hepatic RA
      concentrations to normal levels and modulate hepatocyte hyperproliferation. Male
      Sprague-Dawley rats were divided into four groups: control, ethanol-fed, ethanol
      fed + 50 microg all-trans-RA/kg body wt and ethanol-fed + 100 microg all-trans
      RA/kg body wt. Ethanol was given to rats at 6.2% (v/v) in a liquid diet to
      provide 36% of total caloric intake. Control animals received the same amount of
      liquid diet with isocaloric maltodextrin in place of ethanol. Results show that
      the ethanol treatment in rats for a month significantly increased the mean number
      of proliferating cell nuclear antigen (PCNA)-positive hepatocytes [4.96 +/- 1.36%
      (ethanol-fed) versus 0.29 +/- 0.08% (control), P < 0.05]. This increase was
      associated with the induction of hepatic c-Jun protein (6.5-fold increase) and
      cyclin D1 protein (3-fold increase) in ethanol-fed animals as compared with
      controls. Furthermore, activator protein 1 (AP-1) DNA-binding activity was
      significantly higher in hepatic nuclear extracts from ethanol-fed rats than those
      from controls. In contrast, RA supplementation in ethanol-fed rats raised hepatic
      RA concentration to normal levels and almost completely abolished the ethanol
      enhanced c-Jun, cyclin D and AP-1 DNA-binding activities. Moreover, RA
      supplementation at both doses markedly suppressed the ethanol-induced PCNA
      positive hepatocytes by approximately 80%. These results demonstrate that the
      restoration of hepatic RA concentrations by dietary RA supplementation suppresses
      ethanol-induced hepatocyte proliferation via inhibiting c-Jun overexpression, and
      suggest that RA may play a role in preventing or reversing certain types of
      ethanol-induced liver injury.

PMID- 11470753
TI  - Potent inactivation of representative members of each PKC isozyme subfamily and
      PKD via S-thiolation by the tumor-promotion/progression antagonist glutathione
      but not by its precursor cysteine.
AB  - We recently established that S-glutathiolation of cPKCalpha fully inactivates the
      isozyme, at a stoichiometry of approximately 1 mol GSH/mol cPKCalpha. In this
      report we demonstrate that, in addition to cPKCalpha, six other PKC isozymes that
      are representative of the three subfamilies within the PKC family (cPKCbeta1,
      cPKCbeta2 and cPKCgamma, nPKCdelta and nPKCepsilon and aPKC-zeta) are subject to
      inactivation by S-glutathiolation induced by the thiol-specific oxidant diamide,
      which induces disulfide bridge formation. Among PKD and the seven PKC isozymes
      examined in this report only nPKCdelta has been directly implicated as an
      antagonist of tumor promotion/progression, while several of the kinases have been
      implicated in the mediation of tumor promotion/progression. We report that of the
      kinases examined nPKCdelta was the most resistant to inactivation by diamide
      induced S-glutathiolation. In the absence of GSH only nPKCdelta activity
      exhibited a biphasic response to diamide, with low diamide concentrations
      oxidatively enhancing nPKCdelta activity and higher concentrations inactivating
      the isozyme; the other seven kinases were subject to monophasic, concentration
      dependent, oxidative inactivation by diamide to various extents. The results
      provide evidence that at least some pro-oxidant environments may support the
      potent inactivation of nPKCepsilon and other PKC isozymes implicated in tumor
      promotion/progression by the mechanisms of S-glutathiolation and, in some cases,
      disulfide bridge formation among the isozyme thiols, without inducing substantial
      nPKCdelta inactivation. The results also show that neither the seven PKC isozymes
      examined nor PKD are inactivated by S-cysteinylation under conditions that
      support potent inactivation by S-glutathiolation. This indicates that the
      protection that the tumor promotion/progression antagonist GSH may afford against
      oxidative tumor promotion/progression mechanisms by S-thiolating and inactivating
      PKC isozymes and PKD cannot be afforded by the metabolic GSH precursor cysteine.
      These observations support a role for PKC inactivation via S-glutathiolation in
      the mechanism of tumor promotion/progression antagonism by GSH in pro-oxidant
      environments.

PMID- 11470754
TI  - Presence of benzo[a]pyrene diol epoxide adducts in target DNA leads to an
      increase in UV-induced DNA single strand breaks and supF gene mutations.
AB  - Exposure to DNA damaging agents and mutagens often occurs as combinations of
      agents, or as complex mixtures of chemicals. We found that plasmid DNA adducted
      with benzo[a]pyrene diol epoxide (BPDE) was more susceptible to UV-induced single
      strand breaks than was control DNA. To determine whether the increase in DNA
      damage also applied to mutagenic lesions, the supF gene forward mutation assay
      was used to compare mutations induced by BPDE alone, UVB, UVC, BPDE followed by
      UVB and BPDE followed by UVC. It was found that the mutation frequency for BPDE +
      UVB (1167 in 10(4) transformants) was higher than BPDE alone (12 in 10(4)
      transformants) or UVB alone (446 in 10(4) transformants), and the mutation
      frequency for BPDE + UVC (197 in 10(4) transformants) was higher than BPDE alone
      or UVC alone (26 in 10(4) transformants). For BPDE + UVB and BPDE + UVC there was
      a significant increase in plasmids with multiple mutations. Whilst these indicate
      error prone repair due to the single strand breaks, the different mutation
      frequencies in plasmids treated to give similar levels of strand breaks suggest
      other mechanisms for the mutations in plasmids with single mutation events. The
      spectrum of non-multiple mutations in the two combined treatments included both
      UV signature mutations (GC-->AT as the most common mutation) and BPDE signature
      mutations (GC-->TA and GC-->CG as the most common mutations). However, the
      increase in absolute mutation frequency of BPDE signature mutations between BPDE
      treatment and BPDE + UV treatment was greater than the increase in absolute
      mutation frequency of UV signature mutations, even though the level of BPDE
      adducts was identical in each case. These results suggest two possibilities: (i)
      the BPDE adducts are photoactivated to a more mutagenic lesion, or (ii) the
      presence of UV lesions lead to the BPDE adducts becoming more mutagenic.

PMID- 11470755
TI  - Site specificity and mechanism of oxidative DNA damage induced by carcinogenic
      catechol.
AB  - Catechol, a naturally occurring and an important industrial chemical, has been
      shown to have strong promotion activity and induce glandular stomach tumors in
      rodents. In addition, catechol is a major metabolite of carcinogenic benzene. To
      clarify the carcinogenic mechanism of catechol, we investigated DNA damage using
      human cultured cell lines and 32P-labeled DNA fragments obtained from the human
      p53 and p16 tumor suppressor genes and the c-Ha-ras-1 proto-oncogene. Catechol
      increased the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is
      known to be correlated with the incidence of cancer, in a human leukemia cell
      line HL-60, whereas the amount of 8-oxodG in its hydrogen peroxide (H2O2)
      resistant clone HP100 was not increased. The formation of 8-oxodG in calf thymus
      DNA was increased by catechol in the presence of Cu(2+). Catechol caused damage
      to 32P-labeled DNA fragments in the presence of Cu(2+). When NADH was added, DNA
      damage was markedly enhanced and clearly observed at relatively low
      concentrations of catechol (<1 microM). DNA cleavage was enhanced by piperidine
      treatment, suggesting that catechol plus NADH caused not only deoxyribose
      phosphate backbone breakage but also base modification. Catechol plus NADH
      frequently modified thymine residues. Bathocuproine, a specific Cu(+) chelator
      and catalase inhibited the DNA damage, indicating the participation of Cu(+) and
      H2O2 in DNA damage. Typical hydroxyl radical scavengers did not inhibit catechol
      plus Cu(2+)-induced DNA damage, whereas methional completely inhibited it. These
      results suggest that reactive species derived from the reaction of H2O2 with
      Cu(+) participates in catechol-induced DNA damage. Therefore, we conclude that
      oxidative DNA damage by catechol through the generation of H2O2 plays an
      important role in the carcinogenic process of catechol and benzene.

PMID- 11470756
TI  - Role of transforming growth factor alpha and prostaglandins in preferential
      growth of preneoplastic rat hepatocytes.
AB  - The role of transforming growth factor alpha (TGFalpha) and prostaglandins (PGs)
      in the preferential growth of preneoplastic liver cells was studied. Rats
      received the genotoxic hepatocarcinogen N-nitrosomorpholine (NNM); placental
      glutathione S-transferase (GSTp) was used as a marker to identify preneoplastic
      foci. Preneoplastic foci expressing TGFalpha (TGFalpha(+)) grew more rapidly than
      TGFalpha negative (TGFalpha(-)) ones. Almost all tumours studied were positive
      for TGFalpha. The key enzymes of prostaglandin synthesis, cyclooxygenase I (Cox
      1) and II (Cox-2), were present in all unaltered and preneoplastic cells and
      tended to decrease in the later stages of hepatocarcinogenesis. Immunostaining
      revealed that cultures of hepatocytes, isolated from NNM-treated livers by
      collagenase perfusion, contained 1-2% GSTp-positive (GSTp(+)) and 9% TGFalpha(+)
      hepatocytes; 0.6% of the cells were GSTp(+)/TGFalpha(+). Cox-1 and Cox-2 were
      present in all cells. DNA replication was almost exclusively associated with
      expression of TGFalpha. GSTp(+) hepatocytes showed a 3- to 4-fold higher
      probability of TGFalpha expression and of DNA synthesis than GSTp-negative (GSTp(
      )) cells. PGE(2) or PGF(2alpha) increased expression of TGFalpha and DNA
      replication in GSTp(-) cells but not in GSTp(+) cells. PGA(2) and PGJ(2)
      decreased DNA synthesis in TGFalpha(+) cells without an obvious effect on the
      intracellular levels of TGFalpha. The Cox-2 inhibitor SC236 suppressed DNA
      replication preferentially in GSTp(+) cells; this inhibition was reversed by
      PGE(2)/F(2alpha). Indomethacin had no effect. These results suggest the following
      conclusions. (i) Growth regulation of preneoplastic GSTp(+) cells in culture
      exhibits distinct differences from GSTp(-) cells and elevated expression of
      TGFalpha contributes to their growth advantage. (ii) TGFalpha renders
      preneoplastic hepatocytes sensitive to suppression of DNA synthesis by
      PGA(2)/J(2). (iii) SC236, a Cox-2 inhibitor, may have preventive value in
      hepatocarcinogenesis.

PMID- 11470757
TI  - Aberrant cell cycle checkpoint function in transformed hepatocytes and WB-F344
      hepatic epithelial stem-like cells.
AB  - Cell cycle checkpoints are barriers to carcinogenesis as they function to
      maintain genomic integrity. Attenuation or ablation of checkpoint function may
      enhance tumor formation by permitting outgrowth of unstable cells with damaged
      DNA. To examine the function of cell cycle checkpoints in rat
      hepatocarcinogenesis, we analyzed the responses of the G (1), G (2) and mitotic
      spindle assembly checkpoints in normal rat hepatocytes, hepatic epithelial stem
      like cells (WB-F344) and transformed derivatives of both. Normal rat hepatocytes
      (NRH) displayed a 73% reduction in the fraction of nuclei in early S-phase 6-8 h
      following 8 Gy of ionizing radiation (IR) as a quantitative measure of G (1)
      checkpoint function. Chemically and virally transformed hepatocyte lines
      displayed significant attenuation of G (1) checkpoint function, ranging from
      partial to complete ablation. WB-F344 rat hepatic epithelial cell lines at low,
      mid and high passage levels expressed G (1) checkpoint function comparable with
      NRH. Only one of four malignantly transformed WB-F344 cell lines displayed
      significant attenuation of G (1) checkpoint function. Attenuation of G (1)
      checkpoint function in transformed hepatocytes and WB-F344 cells was associated
      with alterations in p53, ablated/attenuated induction of p21 (Waf1) by IR, as
      well as aberrant function of the spindle assembly checkpoint. NRH displayed 93%
      inhibition of mitosis 2 h after 1 Gy IR as a quantitative measure of G (2)
      checkpoint function. All transformed hepatocyte and WB-F344 cell lines displayed
      significant attenuation of the G (2) checkpoint. Moreover, the parental WB-F344
      line displayed significant age-related attenuation of G (2) checkpoint function.
      Abnormalities in the function of cell cycle checkpoints were detected in
      transformed hepatocytes and WB-F344 cells at stages of hepatocarcinogenesis
      preceding tumorigenicity, sustaining a hypothesis that aberrant checkpoint
      function contributes to carcinogenesis.

PMID- 11470758
TI  - Antiproliferative B cell translocation gene 2 protein is down-regulated post
      transcriptionally as an early event in prostate carcinogenesis.
AB  - B cell translocation gene 2 (BTG2) is a p53 target that negatively regulates cell
      cycle progression in response to DNA damage and other stress. The objective of
      this study was to examine the expression, regulation and tumor suppressor
      properties of BTG2 in prostate cells. By immunohistochemistry BTG2 protein was
      detected in approximately 50% of basal cells in benign glands from the peripheral
      zone of the human prostate. BTG2 was expressed in all hyperproliferative atrophic
      peripheral zone lesions examined (simple atrophy, post-atrophic hyperplasia and
      proliferative inflammatory atrophy), but was undetectable or detectable at very
      low levels in the hyperproliferative epithelial cells of HGPIN and prostate
      cancer. BTG2 mRNA was detected in non-malignant prostate epithelial (PE) cells
      and in LNCaP cells, but not in PC-3 cells, consistent with p53-dependent
      regulation. In PE cells BTG2 protein was detected in areas of cell confluence by
      immunohistochemistry. BTG2 protein in LNCaP cells was undetectable by
      immunohistochemistry but was detected by immunoblotting at 8- to 9-fold lower
      levels than in PE cells. BTG2 protein levels were shown to be regulated by the
      ubiquitin-proteosome system. Forced expression of BTG2 in PC-3 cells was
      accompanied by a decreased rate of cell proliferation and decreased
      tumorigenicity of these cells in vivo. Taken together, these findings suggest
      that BTG2 functions as a tumor suppressor in prostate cells that is activated by
      cell quiescence, cell growth stimuli as part of a positive feedback mechanism and
      in response to DNA damage or other cell stress. The low steady-state levels of
      BTG2 protein in HGPIN and prostate cancer, a potential consequence of increased
      proteosomal degradation, may have important implications in the initiation and
      progression of malignant prostate lesions. Furthermore, these findings suggest
      that a significant component of the p53 G(1) arrest pathway might be inactivated
      in prostate cancer even in the absence of genetic mutations in p53.

PMID- 11470759
TI  - Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of
      mice following infection with Helicobacter hepaticus.
AB  - Helicobacter hepaticus infection is associated with chronic hepatitis and the
      development of liver tumours in mice. The underlying mechanism of this liver
      carcinogenesis is not clear but the oxidative stress associated with H. hepaticus
      infection may result in induction of lipid peroxidation and the generation of
      malondialdehyde. Malondialdehyde can react with deoxyguanosine in DNA resulting
      in the formation of the cyclic pyrimidopurinone N-1,N(2) malondialdehyde
      deoxyguanosine (M1dG) adduct. This adduct has the potential to cause mutations
      that may ultimately lead to liver carcinogenesis. The objective of this study was
      to determine the control and infection-related levels of M1dG in the liver DNA of
      mice over time, using an immunoslot-blot procedure. The level of M1dG in control
      A/J mouse livers at 3, 6, 9 and 12 months averaged 37.5, 36.6, 24.8 and 30.1
      adducts per 10(8) nucleotides, respectively. Higher levels of M1dG were detected
      in the liver DNA of H. hepaticus infected A/JCr mice, with levels averaging 40.7,
      47.0, 42.5 and 52.5 adducts per 10(8) nucleotides at 3, 6, 9 and 12 months,
      respectively. There was a significant age dependent increase in the level of M1dG
      in the caudate and median lobes of the A/JCr mice relative to control mice. A
      lobe specific distribution of the M1dG adduct in both infected and control mice
      was noted, with the left lobe showing the lowest level of the adduct compared
      with the right and median lobes at all time points. In a separate series of mice
      experimentally infected with H. hepaticus, levels of 8-hydroxy-deoxyguanosine
      were significantly greater in the median compared with the left lobe at 12 weeks
      after treatment. In conclusion, these results suggest that M1dG occurs as a
      result of oxidative stress associated with H. hepaticus infection of mice, and
      may contribute to liver carcinogenesis in this model.

PMID- 11470760
TI  - Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with
      susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis
      B carriers: a nested case-control study in Taiwan.
AB  - This study was conducted to investigate the modifying effect of glutathione S
      transferase (GST) M1 and T1 polymorphisms on aflatoxin-induced
      hepatocarcinogenesis among chronic hepatitis B virus surface antigen (HBsAg)
      carriers. A total of 79 HBsAg-positive cases of hepatocellular carcinoma (HCC)
      diagnosed between 1991 and 1997 were identified and individually matched to one
      or two HBsAg-positive controls on age, gender, residence and date of recruitment
      from the same cancer screening cohort in Taiwan. Blood samples were tested for
      hepatitis B and C viral markers by enzyme immunoassay and for aflatoxin B(1)
      (AFB(1))-albumin adducts by competitive enzyme-linked immunosorbent assay. GSTM1
      and GSTT1 genotypes were determined by PCR. There was a statistically significant
      relationship between detectable levels of AFB(1)-albumin adducts in serum and
      risk of HCC among chronic HBsAg carriers, with an adjusted odds ratio (OR) of 2.0
      [95% confidence interval (CI) 1.1-3.7]. In addition, the effect of aflatoxin
      exposure on HCC risk was more pronounced among chronic HBsAg carriers with the
      GSTT1 null genotype (OR 3.7, 95% CI 1.5-9.3) than those who were non-null (OR
      0.9, 95% CI 0.3-2.4). The interaction between serum AFB(1)-albumin adduct level
      and GSTT1 genotype was statistically significant (P = 0.03). For GSTM1 the effect
      of aflatoxin exposure on HCC risk in those with the null genotype was also
      greater (adjusted OR 2.8, 95% CI 1.0-7.8) than in those with the gene present
      (adjusted OR 1.8, 95% CI 0.8-4.5), but the difference was not significant (P =
      0.91). Notably, when the interaction between aflatoxin exposure and GSTT1
      genotype was considered, aflatoxin exposure by itself was not a significant
      determinant of HCC risk among chronic HBsAg carriers. These results demonstrate
      the importance of gene-environment interactions in the multifactorial development
      of HCC.

PMID- 11470761
TI  - Organ dependent enhancement of rat 3,2'-dimethyl-4-aminobiphenyl (DMAB)
      carcinogenesis by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP):
      positive effects on the intestine but not the prostate.
AB  - In order to evaluate tumor enhancing effects of the heterocyclic carcinogen, 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), doses of 100 and 300 p.p.m.
      PhIP were given for 40 weeks to male F344 rats, which initially received 3,2'
      dimethyl-4-aminobiphenyl (DMAB). DMAB shows a similar carcinogenic organ spectrum
      to that of PhIP, including the prostate and colon. PhIP alone at a dose of 300
      p.p.m. resulted in the development of prostate and intestine cancers.
      Furthermore, among the DMAB-treated group, enhancement of intestinal
      carcinogenesis by 300 p.p.m. PhIP was observed. However, no prostate enhancement
      was demonstrated in the DMAB + PhIP group. Since PhIP-DNA adduct formation in the
      prostate epithelial cells in a satellite experiment was not affected by pre
      treatment with DMAB, it is speculated that the contradictory findings between the
      intestine and prostate may be due to the specific biological effects of PhIP.
      Taking into account previous data, that PhIP clearly enhanced rat 1,2
      dimethylhydrazine-initiated colon tumorigenesis, the potential of PhIP to enhance
      colon carcinogenesis may be initiator dependent.

PMID- 11470762
TI  - Role of arginine 216 in catalytic activity of murine Alpha class glutathione
      transferases mGSTAl-1 and mGSTA2-2 toward carcinogenic diol epoxides of
      polycyclic aromatic hydrocarbons.
AB  - Murine class Alpha glutathione (GSH) transferase A1-1 (mGSTA1-1) is unique among
      mammalian Alpha class GSTs due to its exceptionally high catalytic activity
      toward (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)
      anti-BPDE], which is the activated metabolite of an environmentally relevant
      carcinogen, benzo[a] pyrene (BP). However, the molecular basis for high catalytic
      activity of mGSTA1-1 toward (+)-anti-BPDE is not clear. In the present study, we
      demonstrate that an arginine residue at position 216, which is conserved in some
      but not all mammalian class Alpha GSTs, plays an important role in catalytic
      activity of mGSTA1-1 toward (+)-anti-BPDE and carcinogenic diol epoxides of other
      environmentally relevant polycyclic aromatic hydrocarbons (PAHs). The catalytic
      efficiency (k(cat)/K(m)) of mGSTA1-1 for the GSH conjugation of (+)-anti-BPDE
      (108/mM/s) was reduced by about 58% upon replacement of arginine 216 with alanine
      (R216A). This was mainly due to a significantly lower V(max) for the R216A mutant
      of mGSTA1-1 compared with wild-type mGSTA1-1. The R216A mutation also resulted in
      a statistically significant reduction (>70%) in specific activity of mGSTA1-1
      toward racemic anti-diol epoxides of chrysene and benzo[c]phenanthrene (anti-CDE
      and anti-B[c]PDE, respectively). The catalytic activity of mGSTA2-2, which is a
      close structural homologue of mGSTA1-1, was also reduced upon R216A mutation. The
      results of the present study clearly indicate that an arginine residue at
      position 216 is critical for catalytic activity of mGSTA1-1 and mGSTA2-2 toward
      carcinogenic diol epoxide metabolites of various PAHs that are abundant in the
      environment and suspected human carcinogens.

PMID- 11470763
TI  - DNA adduct formation and mutant induction in Sprague-Dawley rats treated with
      tamoxifen and its derivatives.
AB  - The non-steroidal anti-estrogen tamoxifen is used as an adjunct chemotherapeutic
      agent for the treatment of all stages of breast cancer and more recently as a
      chemoprotective agent in women with elevated risk of developing breast cancer.
      While beneficial for the treatment of breast cancer, tamoxifen increases the risk
      of endometrial cancer. In addition, it has been shown to induce liver and
      endometrial tumors in rats. Tamoxifen is genotoxic in rat liver, as indicated by
      the formation of DNA adducts, through a metabolic pathway involving the alpha
      hydroxylation of tamoxifen and N-desmethyltamoxifen. Since the contribution of
      these alpha-hydroxy metabolites of tamoxifen to the induction of endometrial
      tumors is presently unknown, we compared the extent of DNA adduct formation in
      liver and selected non-hepatic tissues of female Sprague-Dawley rats treated by
      gavage with tamoxifen, alpha-hydroxytamoxifen, N-desmethyltamoxifen, alpha
      hydroxy-N-desmethyltamoxifen and N,N-didesmethyltamoxifen, or intraperitoneal
      injection with tamoxifen, alpha-hydroxytamoxifen, 3-hydroxytamoxifen and 4
      hydroxytamoxifen. In addition, spleen lymphocytes from rats treated by gavage
      with tamoxifen or alpha-hydroxytamoxifen were assayed for the induction of
      mutants in the hypoxanthine phosphoribosyl transferase (Hprt) gene. The relative
      levels of binding in rats treated by gavage were alpha-hydroxytamoxifen >
      tamoxifen approximately N-desmethyltamoxifen approximately alpha-hydroxy-N
      desmethyltamoxifen > N,N-didesmethyltamoxifen. In rats dosed intraperitoneally,
      the relative order of binding was alpha-hydroxytamoxifen > tamoxifen > 3
      hydroxytamoxifen approximately 4-hydroxytamoxifen. None of the compounds resulted
      in an increase in DNA adducts in uterus, spleen, thymus or bone marrow DNA from
      rats treated by gavage or in uterus DNA from rats injected intraperitoneally.
      Neither tamoxifen nor alpha-hydroxytamoxifen increased the Hprt mutant frequency
      in spleen T-lymphocytes. These results confirm previous observations that
      tamoxifen is activated to a genotoxic agent in rat liver through alpha
      hydroxylation, and also suggest that endometrial tumors in rats do not arise from
      the formation of tamoxifen-DNA adducts.

PMID- 11470764
TI  - Detection of early gene expression changes by differential display in the livers
      of mice exposed to dichloroacetic acid.
AB  - Dichloroacetic acid (DCA) is a major by-product of water disinfection by
      chlorination. Several studies have demonstrated the hepatocarcinogenicity of DCA
      in mice when administered in drinking water. The mechanism of DCA carcinogenicity
      is not clear and we speculate that changes in gene expression may be important.
      In order to analyze early changes in gene expression induced by DCA treatment we
      used the differential display method. Mice were treated with 2 g/l DCA in
      drinking water for 4 weeks. Total RNAs were obtained from livers of both control
      and treated mice for analysis. Of approximately 48 000 bands on the differential
      display gels representing an estimated 96% of RNA species, 381 showed differences
      in intensity. After cloning and confirmation by both reverse-northern and
      northern analyses, six differentially expressed genes were found. The expression
      of five of these genes was suppressed in the DCA-treated mice while one was
      induced. After sequencing, four genes were identified and two were matched to
      expressed sequence tags through the BLAST program. These genes are alpha-1
      protease inhibitor, cytochrome b5, stearoyl-CoA desaturase and carboxylesterase.
      Stearoyl-CoA desaturase was induced approximately 3-fold in the livers of DCA
      treated mice and the other three genes were suppressed approximately 3-fold.
      Stearoyl-CoA desaturase, cytochrome b5 and carboxylesterase are endoplasmic
      reticulum membrane-bound enzymes involved in fatty acid metabolism. The
      expression pattern of four of these genes was similar in DCA-induced
      hepatocellular carcinomas and the 4 week DCA-treated mouse livers. The expression
      of stearoyl-CoA desaturase and one of the unidentified genes returned to control
      levels in the carcinomas. Understanding the roles and interactions between these
      genes may shed light on the mechanism of DCA carcinogenesis.

PMID- 11470765
TI  - Association of CYP2C9 genotypes leading to high enzyme activity and colorectal
      cancer risk.
AB  - CYP2C9 enzyme activity is involved in the metabolism of substances related to
      colorectal cancer, and it is functionally linked to a genetic polymorphism. Two
      allelic variants of the CYP2C9 gene, namely CYP2C9*2 and CYP2C9*3, differ from
      wild-type CYP2C9*1 by single amino acid substitutions. These mutated alleles
      encode enzymes with altered properties that are associated with impaired
      metabolism. The present study evaluates the impact of CYP2C9 genotypes leading to
      high enzyme activity on colorectal cancer risk. For this, the frequency of
      allelic variants of the CYP2C9 gene was analysed in genomic DNA from 129 patients
      with colorectal cancer and in 150 healthy controls. Patients with colorectal
      cancer showed a statistically significant increase in the frequency of genotypes
      homozygous for the active CYP2C9*1 gene, as compared with healthy individuals.
      Such a high frequency is more significant among patients with cancer in proximal
      segments of the colon (P < 0.025; odds ratio 2.36 95% CI 1.18-4.72), and
      decreases in more distal tumour locations. We conclude that CYP2C9 polymorphism
      can be considered as a secondary risk factor for colorectal cancer in the studied
      population: those individuals with genotypes leading to high enzyme activity were
      at increased risk. The association of the CYP2C9 polymorphism to colorectal
      cancer risk could be related to CYP2C9-mediated metabolic activation of
      polycyclic aromatic hydrocarbons and heterocyclic aromatic amines. In addition,
      the key role of CYP2C9 in the metabolic inactivation of non-steroidal anti-
      inflammatory drugs could diminish the protective effect of these drugs against
      colorectal cancer.

PMID- 11470766
TI  - Glutathione S-transferase mu1 null genotype is associated with K-ras gene
      mutation in lung adenocarcinoma among smokers.
AB  - Glutathione S-transferase mu1 (GSTM1) plays a role in the detoxification of
      benzo[a]pyrene (BP) diol epoxide in tobacco smoke. Individuals who genetically
      lack the GSTM1 gene are likely to have an increased risk of smoking-related lung
      cancers, however, the target oncogenes for mutation are unknown. To investigate
      the relation between GSTM1 genotype and K-ras gene mutation we examined 193
      adenocarcinomas and 119 squamous cell carcinomas of lung. The GSTM1 genotype was
      determined by PCR and K-ras gene mutations at codons 12 and 13 were detected by
      dot-blot hybridization analysis using sequence-specific oligonucleotide probes. K
      ras gene mutations were found in 29 of 312 (9.3%) tumors. All of them arose in
      patients who were habitual smokers. Mutations of the K-ras gene were detected in
      6 of 100 (6%) and 15 of 93 (16.1%) adenocarcinoma cases with the GSTM1(+) and
      GSTM1(-) genotypes, respectively, and the difference was statistically
      significant. These findings suggest that the cause of K-ras gene mutation in
      smokers with lung adenocarcinoma may be in part an accumulation of BP diol
      epoxide which is not well detoxified in individuals with the GSTM1 null genotype.

PMID- 11470767
TI  - Treatment with cathepsin L inhibitor potentiates Th2-type immune response in
      Leishmania major-infected BALB/c mice.
AB  - Prior to the activation of CD4 (+) T cells, exogenous proteins must be digested
      by endo/lysosomal enzymes in antigen-presenting cells (APC) to produce antigenic
      peptides that are able to be presented on class II molecules of the MHC. Studies
      described here inspect the functional significance of cathepsin L inhibition for
      antigen processing and T (h) 1/T (h) 2 differentiation in experimental
      leishmaniasis. We first demonstrated using in vitro systems that cathepsin L is
      one of the candidate endo/lysosomal enzymes in processing of soluble Leishmania
      antigen (SLA) and that its specific inhibitor, CLIK148, modulated the processing
      of SLA. BALB/c mice are known to be susceptible to infection with Leishmania
      major. Interestingly, treatment of BALB/c mice with CLIK148 exacerbated the
      infection by enhancing the development of SLA-specific T (h) 2-type response such
      as production of IL-4 and generation of T (h) 2-dependent specific IgE/IgG1
      antibodies. Moreover, addition of CLIK148 in incubation of a SLA-specific CD4 (+)
      T cell line with APC up-regulated the production of IL-4. However, CLIK148 did
      not exert any direct influence on the function of T cells themselves. Taken
      together, these findings suggest that treatment of host mice with CLIK148 affects
      the processing of SLA in APC, resulting in the potentiation of T (h) 2-type
      immune responses and thus leading to exacerbation of the infection. Furthermore,
      endo/lysosomal cathepsin L was found to be functionally distinct from previously
      described cathepsins B and D.

PMID- 11470768
TI  - Contribution of heat shock proteins to cell protection from complement-mediated
      lysis.
AB  - The possible participation of hsc70 and hsp70 in cellular protection from
      complement damage was studied. Human erythroleukemia K562 cells were pretreated
      with reagents affecting hsc70 or hsp70, and cell sensitivity to lysis by antibody
      and human complement was examined. Treatment with deoxyspergualin, an hsc70
      inhibitor, sensitized K562 cells to complement lysis, whereas treatment with
      ethanol, butanol or hemin, inducers of hsc70 synthesis, protected the cells from
      complement-mediated lysis. Incubation of K562 at either 42 degrees C or with the
      amino acid analogue L-azetidine-2-carboxylic acid induced synthesis of hsp70, but
      not of hsc70. The latter treatment also conferred elevated resistance to
      complement lysis on K562 cells. Pretreatment of K562 cells with sub-lethal doses
      of complement desensitizes them to lethal complement doses. No effect of sublytic
      complement on synthesis of hsc70 and hsp70 was found. However, the results
      demonstrated that complement stress causes translocation of hsc70 from the
      cytoplasm to the K562 cell surface. Two monoclonal and two polyclonal antibodies
      identified hsc70 on the surface of intact, viable complement-stressed cells,
      while antibodies directed to hsp70 did not bind to these cells. Altogether, the
      results suggest that the heat shock proteins hsc70 and hsp70 play a role in cell
      defense against complement.

PMID- 11470769
TI  - The MHC class I-related receptor, FcRn, plays an essential role in the
      maternofetal transfer of gamma-globulin in humans.
AB  - The transfer of maternal gamma-globulin (IgG) provides the neonate with humoral
      immunity during early life. In humans, maternal IgG is transported across the
      placenta during the third trimester of pregnancy. The expression of the MHC class
      I-related receptor, FcRn, in the human placenta suggests that this Fc receptor
      might be involved in the delivery of maternal IgG, but direct evidence to support
      this is lacking. In the current study an ex vivo placental model has been used to
      analyze the maternofetal transfer of a recombinant, humanized (IgG1) antibody in
      which His435 has been mutated to alanine (H435A). In vitro binding studies using
      surface plasmon resonance indicate that the mutation ablates binding of the
      antibody to recombinant mouse and human FcRn. Relative to the wild-type antibody,
      the H435A mutant is deficient in transfer across the placenta. Significantly, the
      mutation does not affect binding to Fc gamma RIII, an FcR that has been suggested
      in earlier studies to mediate the transfer of maternal IgG. The analyses
      demonstrate that binding of an IgG to FcRn is a prerequisite for transport across
      the perfused placenta. FcRn therefore plays a central role in the maternofetal
      delivery of IgG and this has implications for the use of protein engineering to
      improve the properties of therapeutic antibodies.

PMID- 11470770
TI  - Deletional analyses reveal an essential role for the hs3b/hs4 IgH 3' enhancer
      pair in an Ig-secreting but not an earlier-stage B cell line.
AB  - The Ig heavy chain (IgH) locus is controlled by multiple regulatory sequences
      mapping both within the IgH transcription unit (E mu) and downstream (3') of IgH
      coding sequences (hs3a, hs1,2, hs3b and hs4). Enhancer knockout studies in mice
      have implicated E mu in the control of IgH variable region gene assembly, but
      single-enhancer knockouts involving the 3' IgH enhancers have yet to shed light
      on their function. Transfection studies in mice and cell lines have suggested
      that the 3' enhancers behave similarly to a locus control region as first
      identified in the beta-globin locus. We have exploited this property to form mini
      loci in a surface Ig(+) and an Ig-secreting cell line as a means for studying the
      functions of the 3' IgH enhancers. Importantly, this experimental system allows
      for the analysis of enhancer function within the context of chromatin. The mini
      loci consisted of an Ig gamma 2b transcription unit linked to the four murine 3'
      IgH enhancers. Using targeted deletions of enhancer pairs within these mini-loci,
      we have discovered a critical and apparently developmentally regulated role for
      the hs3b/hs4 enhancer pair in IgH transgene expression.

PMID- 11470771
TI  - CpG DNA induces cyclooxygenase-2 expression and prostaglandin production.
AB  - Unmethylated CpG motifs found in bacterial DNA are potent activators of the
      innate and acquired immune systems, and rapidly induce the production of
      proinflammatory cytokines. We hypothesized that CpG DNA may also elicit the
      production of prostaglandins (PG), which are central lipid mediators of the
      immune and inflammatory response. To test our hypothesis, we stimulated murine
      spleen cells and RAW 264.7 murine macrophage cells with CpG DNA and assessed the
      effects on the PG synthesis pathway. Compared to control, DNA-containing CpG
      motifs induced >5-fold increase in PGE (2) production and rapidly up-regulated
      cyclooxygenase-2 (COX-2) at both the mRNA and protein level. CpG DNA was an
      extremely strong inducer of COX-2 as concentrations as low as 3 ng/ml induced COX
      2 protein expression. The CpG DNA-induced PGE (2) down-regulated the immune
      response elicited by CpG. Blockade of PGE (2) production with selective COX-2
      inhibitors or neutralizing anti-PGE (2) antibody markedly enhanced IFN-gamma
      secretion in vitro from CpG DNA-stimulated spleen cells. Moreover, selective COX
      2 inhibition increased CpG DNA-induced IFN-gamma secretion in vivo. Inhibition of
      COX-2 also increased CpG DNA-induced lytic activity of NK cells. Taken together,
      these data indicate that DNA containing CpG motifs is a potent inducer of COX-2
      and PGE (2) production. CpG-induced PG may subsequently down-regulate the immune
      and inflammatory responses elicited by the CpG DNA.

PMID- 11470772
TI  - Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for
      CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes.
AB  - Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine selectively
      expressed in the liver. Here, we investigated its receptor usage by calcium
      mobilization and chemotactic assays using mouse L1.2 pre-B cell lines stably
      expressing a panel of 12 human chemokine receptors. At relatively high
      concentrations, LEC induced calcium mobilization and chemotaxis via CCR1 and
      CCR2. LEC also induced calcium mobilization, but marginal chemotaxis via CCR5.
      Consistently, LEC was found to bind to CCR1, CCR2 and CCR5 with relatively low
      affinities. The binding of LEC to CCR8 was much less significant. In spite of its
      binding to CCR5, LEC was unable to inhibit infection of an R5-type HIV-1 to
      activated human peripheral blood mononuclear cells even at high concentrations.
      In human liver sections, hepatocytes were strongly stained by anti-LEC antibody.
      HepG2, a human hepatocarcinoma cell line, was found to constitutively express
      LEC. LEC was also present in the plasma samples from healthy adult donors at
      relatively high concentrations (0.3--4 nM). Taken together, LEC is a new low
      affinity functional ligand for CCR1, CCR2 and CCR5, and is constitutively
      expressed by liver parenchymal cells. The presence of LEC in normal plasma at
      relatively high concentrations may modulate inflammatory responses.

PMID- 11470773
TI  - Expression and selection of productively rearranged TCR beta VDJ genes are
      sequentially regulated by CD3 signaling in the development of NK1.1(+) alpha beta
      T cells.
AB  - The generation of thymic NK1.1(+)alpha beta T (NKT) cells involves positive
      selection of cells enriched for V(alpha)14/V(beta)8 TCR by CD1d MHC class I
      molecules. However, it has not been determined whether positive selection is
      preceded by pre-TCR-dependent beta selection. Here we studied NKT cell
      development in CD3 signaling-deficient mice (CD3 zeta/eta(-/-) and/or p56(lck-/
      )) and TCR alpha-deficient mice. In contrast to wild-type mice, NK1.1(+)
      thymocytes in CD3 signaling-deficient mice are approximately 10-fold reduced in
      number, do not exhibit V(alpha)14-J(alpha)281 rearrangements and fail to express
      alpha beta TCR at the cell surface. However, they exhibit TCR beta VDJ
      rearrangements and pre-T alpha mRNA, suggesting that they contain pre-NKT cells.
      Strikingly, pre-NKT cells of CD3 zeta/Lck double-deficient mice fail to express
      TCR beta mRNA and protein. Whereas in wild-type NKT cells TCR beta VDJ junctions
      are selected for productive V(beta)8 and against productive V(beta)5
      rearrangements, V(beta)8 and V(beta)5 rearrangements are non-selected in pre-NKT
      cells of CD3 signaling-deficient mice. Thus, pre-NKT cell development in CD3
      signaling-deficient mice is blocked after rearrangement of TCR beta VDJ genes but
      before expression of TCR beta proteins. Most NKT cells of TCR alpha-deficient
      mice exhibit cell surface gamma delta TCR. In contrast to pre-NKT cells of CD3
      signaling-deficient mice, approximately 25% of NKT cells of TCR alpha-deficient
      mice exhibit intracellular TCR beta polypeptide chains. Moreover, both V(beta)8
      and V(beta)5 families are selected for in-frame VDJ joints in the TCR beta(+) NKT
      cell subset of TCR alpha-deficient mice. The data suggest that CD3 signals
      regulate initial TCR beta VDJ gene expression prior to beta selection in
      developing pre-NKT cells.

PMID- 11470774
TI  - Biphasic response of NK cells expressing both activating and inhibitory killer Ig
      like receptors.
AB  - NK cells can co-express inhibitory and activating killer Ig-like receptors (KIR)
      recognizing the same HLA class I ligand. We present evidence from experiments
      with NK cells expressing both activating (KIR2DS2) and inhibitory (KIR2DL2 and
      KIR2DL3) receptors that the activating KIR can function without apparent
      interference from the inhibitory KIR. These studies used CD158b mAb that is
      equally reactive with KIR2DS2, KIR2DL2 and KIR2DL3. First, we show using plastic
      immobilized CD158b mAb that the activating KIR2DS2 is stimulated, resulting in NK
      cell division and degranulation. Second, we show using soluble CD158b mAb and
      FcRII (+) P815 cells that high concentrations of CD158b mAb trigger the
      inhibitory KIR, whereas low concentrations stimulate the activating KIR2DS2
      resulting in NK cell division and cytolysis. These results demonstrate that the
      activating KIR2DS2 can function on cells co-expressing the inhibitory KIR2DL2
      and/or KIR2DL3, indicating the potential for independent function of activating
      KIR with natural ligand.

PMID- 11470775
TI  - IL-1 beta induces dendritic cells to produce IL-12.
AB  - The cytokine IL-12, a product of dendritic cells (DC), plays a major role in
      cellular immunity, notably by inducing lymphocytes to produce IFN-gamma.
      Microbial products, T cell signals and cytokines induce the production of IL-12.
      Here, IL-1 beta is identified as a new IL-12-inducing agent, acting conjointly
      with CD40 ligand (CD40L) on human monocyte-derived DC in vitro. The effects of IL
      1 beta were dose dependent, specifically blocked by neutralizing antibodies, and
      were observed both in immature and mature DC. Immature DC secreted more IL-12
      than mature DC, but the effects of IL-1 beta were not due to a block of DC
      maturation as determined by analysis of DC surface markers. The mechanisms of
      action of IL-1 beta could be contrasted to that of other inducers of IL-12 such
      as IFN-gamma and lipopolysaccharide (LPS). Either IL-1 beta or IFN-gamma co
      induced IL-12 with CD40L but conjointly, IL-1 beta, CD40L and IFN-gamma
      synergized, inducing very high levels of IL-12. The effects of IL-1 beta differed
      from those of LPS in that IL-1 beta, unlike LPS, could not induce IL-12 solely
      after IFN-gamma priming; and when combined with CD40L, IL-1 beta, unlike LPS,
      induced little IL-10. The mechanism of action of IL-1 beta involves IL-12 alpha
      mRNA up-regulation, and we show that the combination of CD40L and IL-1 beta
      induces high levels of IL-12 alpha and IL-12 beta mRNA in DC. Altogether, these
      results delineate a new mechanism linking adaptive and innate immune responses
      for the regulation of IL-12 production in DC and for the role of IL-1 beta in the
      development of cellular immunity.

PMID- 11470776
TI  - Distinct differences in association of MHC class I with endoplasmic reticulum
      proteins in wild-type, and beta 2-microglobulin- and TAP-deficient cell lines.
AB  - In this study we have compared the interaction of human MHC class I molecules
      with IgG heavy chain (HC) binding protein (BiP), calnexin, calreticulin, tapasin
      and TAP in beta(2)-microglobulin (beta(2)m)- or TAP-deficient cells, as well as
      in wild-type B-LCL cells. Distinct differences between the association of HC and
      these endoplasmic reticulum (ER) proteins were found in the three cell lines. In
      the absence of beta(2)m (Daudi cells), HC associated with both BiP and calnexin.
      A prominent portion of HC was complexed simultaneously to both chaperones, as
      indicated by co-precipitation with either anti-calnexin or anti-class I antisera.
      In the presence of beta(2)m, but absence of TAP (T2 cells), HC could be co
      precipitated with calnexin, whereas no detectable interaction with BiP could be
      demonstrated. This suggests that calnexin interacts with HC at a later stage than
      BiP. In B-LCL cells, HC-beta(2)m associated with calreticulin and tapasin,
      whereas no interaction with calnexin and BiP was observed. In the absence of
      beta(2)m, HC were rapidly degraded in the ER, while the ER retained HC were
      stabilized in the presence of beta(2)m, even in the absence of TAP. The
      dissociation of class I molecules from TAP in B-LCL cells correlated with the
      kinetics of appearance of class I molecules on the cell surface, suggesting that
      TAP retains peptide-free class I molecules in the ER. Taken together, our results
      suggest the model that BiP and calnexin sequentially control the folding of MHC
      class I, before MHC class I molecules associate with the loading complex.

PMID- 11470777
TI  - Characterization of the human Fc gamma RIIB gene promoter: human zinc-finger
      proteins (ZNF140 and ZNF91) that bind to different regions function as
      transcription repressors.
AB  - Expression of the human low-affinity Fc receptors for IgG (human Fc gamma RII) is
      differentially regulated. We report here the characterization of the promoter
      structure of the human Fc gamma RIIB gene and the isolation of the promoter
      region-binding proteins by a yeast one-hybrid assay. The minimal 154-bp region
      upstream from the transcription start site of the human Fc gamma RIIB gene was
      shown to possess promoter activity in a variety of cells. An electrophoretic
      mobility shift assay indicated that multiple nuclear factors in cell extracts
      bind to the two regions [F2-3 (-110 to -93) and F4-3 (-47 to -31)] of the human
      Fc gamma RIIB gene promoter. Mutation analysis indicated that GGGAGGAGC (-105 to 
      97) and AATTTGTTTGCC (-47 to -36) sequences are responsible for binding to
      nuclear factors respectively. By using GGGAGGAGC and AATTTGTTTGCC as bait
      sequences, we cloned two zinc-finger proteins (ZNF140 and ZNF91) that bind to the
      F2-3 and F4-3 regions within the promoter of the human Fc gamma RIIB gene
      respectively. When the ZNF140 and ZNF91 were transfected with reporter plasmid,
      both showed repressor activity with additive effects. Thus, these results
      indicate that these cloned ZNF140 and ZNF91 proteins function as repressors for
      the human Fc gamma RIIB transcription.

PMID- 11470778
TI  - Altered functional and biochemical response by CD8+ T cells that remain after
      tolerance.
AB  - To further define the molecular basis of tolerance to a peripherally expressed
      antigen we have correlated differences in functional capacity with biochemical
      events in hemagglutinin (HA)-specific cytotoxic T lymphocyte (CTL) clones derived
      either from a conventional B10.D2 mouse that is not tolerant to HA (D2 Clone 6)
      or from an InsHA mouse that is tolerant to HA (InsHA Clone 12). D2 Clone 6, but
      not InsHA Clone 12, triggers diabetes following in vivo transfer into irradiated
      InsHA hosts. This diabetogenic clone shows complete and sustained phosphorylation
      of TCR zeta chain and ZAP-70 following stimulation with HA-pulsed antigen
      presenting cells. In contrast, InsHA Clone 12 showed only partial phosphorylation
      of TCR zeta and no phosphorylation of ZAP-70. There was no defect in activation
      or recruitment of Lck to the TCR complex in both the clones following stimulation
      with the cognate antigen. This deficiency in the proximal signaling in the InsHA
      Clone 12 could be overcome by increasing the strength of signal through the CD3
      TCR complex, indicating that the signaling machinery of InsHA Clone 12 was
      functional. These data demonstrate that the HA-responsive CD8(+) T cells that can
      be retrieved from InsHA mice after tolerance induction respond to HA as a partial
      agonist/antagonist.

PMID- 11470779
TI  - Akt serine threonine kinase regulates platelet-derived growth factor-induced DNA
      synthesis in glomerular mesangial cells: regulation of c-fos AND p27(kip1) gene
      expression.
AB  - Proliferation of mesangial cells requires platelet-derived growth factor receptor
      beta (PDGFR)-mediated signal transduction. We have previously shown that
      activation of phosphatidylinositol (PI) 3-kinase is necessary for PDGFR-induced
      DNA synthesis in these cells. The mechanism by which PI 3-kinase stimulates DNA
      synthesis is not known. One target of PI 3-kinase, Akt serine threonine kinase,
      regulates survival of many cells by inhibiting the actions of certain
      proapoptotic proteins. In this study, we investigated the role of Akt in PDGF
      induced DNA synthesis in mesangial cells. PDGF increased Akt serine threonine
      kinase activity in a time- and PI 3-kinase-dependent manner. Expression of
      dominant negative Akt by adenovirus-mediated gene transfer blocked PDGF-induced
      activation of endogenous Akt in mesangial cells, resulting in complete inhibition
      of DNA synthesis. On the other hand, inhibition of MAPK attenuated PDGF-induced
      DNA synthesis only partially. Inhibition of Akt also attenuated PDGF-induced c
      fos gene transcription, with concomitant inhibition of Elk-1-dependent
      transcription, indicating positive regulation of this early response gene by Akt.
      To further determine the role of Akt in PDGF-induced DNA synthesis, we
      investigated its effect on cyclin-dependent kinase 2 (CDK2). PDGF stimulated CDK2
      activity in mesangial cells and decreased the level of p27(kip1) cyclin kinase
      inhibitor protein. Expression of dominant negative Akt increased p27(kip1)
      protein and resulted in inhibition of CDK2 activity. The increase in p27(kip1)
      expression in response to Akt kinase inhibition was due to increased
      transcription of the p27(kip1) gene. p27(kip1) transcription similarly was
      decreased by expression of constitutively active Akt kinase in mesangial cells.
      These data provide the first evidence that Akt kinase regulates PDGF-induced DNA
      synthesis by regulating CDK2 activity and define Akt-mediated inhibition of
      transcription of p27(kip1) as one of the mechanisms for PDGF-induced DNA
      synthesis in mesangial cells.

PMID- 11470780
TI  - Copper specifically regulates intracellular phosphorylation of the Wilson's
      disease protein, a human copper-transporting ATPase.
AB  - Copper is a trace element essential for normal cell homeostasis. The major
      physiological role of copper is to serve as a cofactor to a number of key
      metabolic enzymes. In humans, genetic defects of copper distribution, such as
      Wilson's disease, lead to severe pathologies, including neurodegeneration, liver
      lesions, and behavior abnormalities. Here, we demonstrate that, in addition to
      its role as a cofactor, copper can regulate important post-translational events
      such as protein phosphorylation. Specifically, in human cells copper modulates
      phosphorylation of a key copper transporter, the Wilson's disease protein (WNDP).
      Copper-induced phosphorylation of WNDP is rapid, specific, and reversible and
      correlates with the intracellular location of this copper transporter. WNDP is
      found to have at least two phosphorylation sites, a basal phosphorylation site
      and a site modified in response to increased copper concentration. Comparative
      analysis of WNDP, the WNDP pineal isoform, and WNDP C-terminal truncation mutants
      revealed that the basal phosphorylation site is located in the C-terminal
      Ser(796)-Tyr(1384) region of WNDP. The copper-induced phosphorylation appears to
      require the presence of the functional N-terminal domain of this protein. The
      novel physiological role of copper as a modulator of protein phosphorylation
      could be central to understanding how copper transport is regulated in mammalian
      cells.

PMID- 11470781
TI  - Real-time visualization of processive myosin 5a-mediated vesicle movement in
      living astrocytes.
AB  - Recycling endosomes in astrocytes show hormone-regulated, actin fiber-dependent
      delivery to the endosomal sorting pool. Recycling vesicle trafficking was
      followed in real time using a fusion protein composed of green fluorescent
      protein coupled to the 29-kDa subunit of the short-lived, membrane-bound enzyme
      type 2 deiodinase. Primary endosomes budded from the plasma membrane and
      oscillated near the cell periphery for 1-4 min. The addition of thyroid hormone
      triggered the processive, centripetal movement of the recycling vesicle in linear
      bursts at velocities of up to 200 nm/s. Vesicle migration was hormone-specific
      and blocked by inhibitors of actin polymerization and myosin ATPase. Domain
      mapping confirmed that the hormone-dependent vesicle-binding domain was located
      at the C terminus of the motor. In addition, the interruption of normal
      dimerization of native myosin 5a monomers inactivated vesicle transport,
      indicating that single-headed myosin 5a motors do not transport cargo in situ.
      This is the first demonstration of processive hormone-dependent myosin 5a
      movement in living cells.

PMID- 11470782
TI  - Shedding of membrane type matrix metalloproteinase 5 by a furin-type convertase:
      a potential mechanism for down-regulation.
AB  - The shedding of membrane-associated proteins has been recognized as a regulatory
      mechanism to either up-regulate or down-regulate cellular functions by releasing
      membrane-bound growth factors or removing ectodomains of adhesion molecules and
      receptors. We have reported previously that the ectoenzyme of membrane type
      matrix metalloproteinase 5 (MT5-MMP) is shed into extracellular milieu (Pei, D.
      (1999) J. Biol. Chem. 274, 8925-8932). Here we present evidence that MT5-MMP is
      shed by a furin-type convertase activity in the trans-Golgi network. Among
      proteinase inhibitors screened, only decanoyl-Arg-Val-Lys-Arg-chloromethylketone,
      a known inhibitor for furin-type convertases, blocked the shedding of MT5-MMP in
      a dose-dependent manner. As expected, decanoyl-Arg-Val-Lys-Arg-chloromethylketone
      also prevented the activation of MT5-MMP, raising the possibility that the
      observed shedding could be autolytic. However, an active site mutant devoid of
      any catalytic activity, is also shed efficiently, thus ruling out the autolytic
      pathway. The shedding cleavage was subsequently mapped to the stem region
      immediately upstream of the transmembrane domain, where a cryptic furin
      recognition site, (545)RRKERR, was recognized. Indeed, MT5-MMP and furin are co
      localized in the trans-Golgi network and the shed species could be detected
      inside the cells. Furthermore, deletion mutations removing this cryptic site
      prevented MT5-MMP from shedding. The resulting mutants express a gain-of-function
      phenotype by mediating more robust activation of proMMP-2 than the wild type
      molecule. Thus, shedding provides a potential mechanism to regulate proteolytic
      activity of membrane-bound MMPs.

PMID- 11470783
TI  - p53 Phosphorylation at serine 15 is required for transcriptional induction of the
      plasminogen activator inhibitor-1 (PAI-1) gene by the alkylating agent N-methyl
      N'-nitro-N-nitrosoguanidine.
AB  - The alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a widely
      spread environmental carcinogen that causes DNA lesions leading to cell killing.
      MNNG can also induce a cell-protective response by inducing the expression of DNA
      repair/transcription-related genes. We recently demonstrated that urokinase-type
      plasminogen activator, an extracellular protease to which no DNA repair functions
      have been assigned, was induced by MNNG. Here, we show that the physiological
      inhibitor of urokinase-type plasminogen activator, PAI-1, is also induced by MNNG
      in a p53-dependent fashion, because MNNG induced PAI-1 in p53-expressing cells
      but not in p53-/- cells. MNNG induced p53 phosphorylation at serine 15, resulting
      in stabilization of the p53 protein, and this phosphorylation event was central
      for p53-dependent PAI-1 transcription. Finally, we showed that PAI-1
      transcriptional induction by MNNG required a p53-responsive element located at 
      136 base pairs in the PAI-1 promoter, because specific mutation of this site
      abrogated the induction. Because PAI-1 is a prognostic factor in many metastatic
      cancers, being involved in the control of tumor invasiveness, our finding that a
      genotoxic agent induces the PAI-1 gene via p53 adds a new feature to the role of
      the tumor-suppressor p53 protein. Our results also suggest the possibility that
      genotoxic agents contribute to tumor metastasis by inducing PAI-1 without
      involving genetic modification.

PMID- 11470784
TI  - An isoform-specific inhibitory domain regulates the LHX3 LIM homeodomain factor
      holoprotein and the production of a functional alternate translation form.
AB  - The LHX3 LIM homeodomain transcription factor is required for pituitary
      development and motor neuron specification. The Lhx3 gene encodes two isoforms,
      LHX3a and LHX3b, that differ in their amino-terminal sequences. Humans and mice
      with defective Lhx3 genes are deficient in gonadotrope, lactotrope, somatotrope,
      and thyrotrope pituitary cells. We show that, whereas Lhx3b is highly expressed
      in these Lhx3-dependent cell types, high levels of Lhx3a expression are
      restricted to alpha glycoprotein subunit-expressing thyrotropes and gonadotropes.
      Cross-species comparison reveals the LHX3b-specific domain is more conserved than
      the LHX3a-specific domain. We demonstrate that the LHX3b-specific domain is a
      transferable inhibitor that reduces gene activation and DNA binding by
      homeodomain proteins. In addition, we identify a novel LHX3 protein (M2-LHX3) and
      determine that this molecule is generated by an internal translation initiation
      codon. The LHX3a- and LHX3b-specific coding sequences regulate differential usage
      of this internal start codon. Further, we identify the major activation domain of
      LHX3 in the carboxyl terminus of the molecule. M2-LHX3 is active because it
      retains this domain and binds DNA better than LHX3a or LHX3b. Other LIM
      homeodomain genes, including Lhx4, generate similar truncated proteins. These
      studies describe how transcriptional regulatory genes can generate multiple
      functional proteins.

PMID- 11470785
TI  - K(+)-independent gastric H(+),K(+)-atpase activity. Dissociation of K(+)
      independent dephosphorylation and preference for the E1 conformation by combined
      mutagenesis of transmembrane glutamate residues.
AB  - Several mutations of residues Glu(795) and Glu(820) present in M5 and M6 of the
      catalytic subunit of gastric H(+),K(+)-ATPase have resulted in a K(+)
      independent, SCH 28080-sensitive ATPase activity, caused by a high spontaneous
      dephosphorylation rate. The mutants with this property also have a preference for
      the E(1) conformation. This paper investigates the question of whether these two
      phenomena are coupled. This possibility was studied by combining mutations in
      residue Glu(343), present in M4, with those in residues 795 and 820. When in
      combined mutants Glu and/or Gln residues were present at positions 343, 795, and
      820, the residue at position 820 dominated the behavior: a Glu giving K(+)
      activated ATPase activity and an E(2) preference and a Gln giving K(+)
      independent ATPase activity and an E(1) preference. With an Asp at position 343,
      the enzyme could be phosphorylated, but the dephosphorylation was blocked,
      independent of the presence of either a Glu or a Gln at positions 795 and 820.
      However, in these mutants, the direction of the E(2) <--> E(1) equilibrium was
      still dominated by the 820 residue: a Glu giving E(2) and a Gln giving E(1). This
      indicates that the preference for the E(1) conformation of the E820Q mutation is
      independent of an active dephosphorylation process.

PMID- 11470786
TI  - Recruitment of a foreign quinone into the A1 site of photosystem I. In vivo
      replacement of plastoquinone-9 by media-supplemented naphthoquinones in
      phylloquinone biosynthetic pathway mutants of Synechocystis sp. PCC 6803.
AB  - Interruption of the phylloquinone (PhQ) biosynthetic pathway by interposon
      mutagenesis of the menA and menB genes in Synechocystis sp. PCC 6803 results in
      plastoquinone-9 (PQ-9) occupying the A(1) site and functioning in electron
      transfer from A(0) to the FeS clusters in photosystem (PS) I (Johnson, T. W.,
      Shen, G., Zybailov, B., Kolling, D., Reategui, R., Beauparlant, S., Vassiliev, I.
      R., Bryant, D. A., Jones, A. D., Golbeck, J. H., and Chitnis, P. R. (2000) J.
      Biol. Chem. 275, 8523-8530. We report here the isolation of menB26, a strain of
      the menB mutant that grows in high light by virtue of a higher PS I to PS II
      ratio. PhQ can be reincorporated into the A(1) site of the menB26 mutant strain
      by supplementing the growth medium with authentic PhQ. The reincorporation of PhQ
      also occurs in cells that have been treated with protein synthesis inhibitors,
      consistent with a displacement of PQ-9 from the A(1) site by mass action. The
      doubling time of the menB26 mutant cells, but not the menA mutant cells,
      approaches the wild type when the growth medium is supplemented with
      naphthoquinone (NQ) derivatives such as 2-CO(2)H-1,4-NQ and 2-CH(3)-1,4-NQ. Since
      PhQ replaces PQ-9 in the supplemented menB26 mutant cells, but not in the menA
      mutant cells, the phytyl tail accompanies the incorporation of these quinones
      into the A(1) site. Studies with menB26 mutant cells and perdeuterated 2-CH(3)
      1,4-NQ shows that phytylation occurs at position 3 of the NQ ring because the
      deuterated 2-methyl group remains intact. Therefore, the specificity of the
      phytyltransferase enzyme is selective with respect to the group present at ring
      positions 2 and 3. Supplementing the growth medium of menB26 mutant cells with
      1,4-NQ also leads to its incorporation into the A(1) site, but typically without
      either the phytyl tail or the methyl group. These findings open the possibility
      of biologically incorporating novel quinones into the A(1) site by supplementing
      the growth medium of menB26 mutant cells.

PMID- 11470787
TI  - Complete reconstitution of human IkappaB kinase (IKK) complex in yeast.
      Assessment of its stoichiometry and the role of IKKgamma on the complex activity
      in the absence of stimulation.
AB  - The IkappaB kinase (IKK) complex, composed of two catalytic subunits (IKKalpha
      and IKKbeta) and a regulatory subunit (IKKgamma), is the key enzyme in activation
      of nuclear factor kappaB (NF-kappaB). To study the mechanism and structure of the
      complex, we wanted to recombinantly express IKK in a model organism that lacks
      IKK. For this purpose, we have recombinantly reconstituted all three subunits
      together in yeast and have found that it is biochemically similar to IKK isolated
      from human cells. We show that there is one regulatory subunit per kinase
      subunit. Thus, the core subunit composition of IKKalpha.beta.gamma complex is
      alpha(1)beta(1)gamma(2), and the core subunit composition of IKKbeta.gamma is
      beta(2)gamma(2). The activity of the IKK complex (alpha+beta+gamma or beta+gamma)
      expressed in yeast (which lack NF-kappaB and IKK) is 4-5-fold higher than an
      equivalent amount of IKK from nonstimulated HeLa cells. In the absence of
      IKKgamma, IKKbeta shows a level of activity similar to that of IKK from
      nonstimulated HeLa cells. Thus, IKKgamma activates IKK complex in the absence of
      upstream stimuli. Deleting the gamma binding domain of IKKbeta or IKKalpha
      prevented IKKgamma induced activation of IKK complex in yeast, but it did not
      prevent the incorporation of IKKgamma into IKK and large complex formation. The
      possibility of IKK complex being under negative control in mammalian cells is
      discussed.

PMID- 11470788
TI  - IKKgamma /NEMO facilitates the recruitment of the IkappaB proteins into the
      IkappaB kinase complex.
AB  - IKKgamma/NEMO is an essential regulatory component of the IkappaB kinase complex
      that is required for NF-kappaB activation in response to various stimuli
      including tumor necrosis factor-alpha and interleukin-1beta. To investigate the
      mechanism by which IKKgamma/NEMO regulates the IKK complex, we examined the
      ability of IKKgamma/NEMO to recruit the IkappaB proteins into this complex.
      IKKgamma/NEMO binding to wild-type, but not to a kinase-deficient IKKbeta
      protein, facilitated the association of IkappaBalpha and IkappaBbeta with the
      high molecular weight IKK complex. Following tumor necrosis factor-alpha
      treatment of HeLa cells, the majority of the phosphorylated form of endogenous
      IkappaBalpha was associated with the high molecular weight IKK complex in HeLa
      cells and parental mouse embryo fibroblasts but not in IKKgamma/NEMO-deficient
      cells. Finally, we demonstrate that IKKgamma/NEMO facilitates the association of
      the IkappaB proteins and IKKbeta and leads to increases in IKKbeta kinase
      activity. These results suggest that an important function of IKKgamma/NEMO is to
      facilitate the association of both IKKbeta and IkappaB in the high molecular
      weight IKK complex to increase IkappaB phosphorylation.

PMID- 11470789
TI  - Characterization and functional implications of the RNA binding properties of
      nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9.
AB  - Variations in a polymorphic (TG)m sequence near exon 9 of the human CFTR gene
      have been associated with variable proportions of exon skipping and occurrence of
      disease. We have recently identified nuclear factor TDP-43 as a novel splicing
      regulator capable of binding to this element in the CFTR pre-mRNA and inhibiting
      recognition of the neighboring exon. In this study we report the dissection of
      the RNA binding properties of TDP-43 and their functional implications in
      relationship with the splicing process. Our results show that this protein
      contains two fully functional RNA recognition motif (RRM) domains with distinct
      RNA/DNA binding characteristics. Interestingly, TDP-43 can bind a minimum number
      of six UG (or TG) single-stranded dinucleotide stretches, and binding affinity
      increases with the number of repeats. In particular, the highly conserved Phe
      residues in the first RRM region play a key role in nucleic acid recognition.

PMID- 11470790
TI  - PKCtheta II, a new isoform of protein kinase C specifically expressed in the
      seminiferous tubules of mouse testis.
AB  - Protein kinase C (PKC) theta, a Ca(2+)-independent isoform of PKC, has been known
      to be expressed in skeletal muscle and T cells. In the present study, we isolated
      and characterized a smaller transcript expressed in the mouse testis, the cDNA of
      which is referred hereafter as PKCthetaII and the original PKCtheta as PKCthetaI.
      The cDNA clone of PKCthetaII has 2184 base pairs and 464 amino acids in the
      possible open reading frame, consisting of the 5' unique sequence of 20 amino
      acids and the PKCthetaI sequence of 444 amino acids. Genomic DNA analysis
      revealed that transcription of PKCthetaII is initiated from the PKCthetaII
      specific exon, which is located between exons 7 and 8 of the PKCtheta gene,
      indicating that alternative splicing is the mechanism by which PKCthetaII is
      generated. PKCthetaII is expressed exclusively in the testis in an age-dependent
      manner with sexual maturation. In situ hybridization and reverse transcription
      polymerase chain reaction of microdissected tissues clearly demonstrated that
      PKCthetaII is expressed in the seminiferous tubules of the mouse testis.
      Consistent with its molecular structure lacking the C1 regulatory domain,
      PKCthetaII is constitutively active as determined by an in vitro kinase assay,
      being independent of PKC activators, e.g. phosphatidylserine and phorbol ester.
      PKCthetaII may play a crucial role in spermatogenesis or some related function of
      the testis.

PMID- 11470791
TI  - The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent
      intracellular trafficking.
AB  - In C2C12 myoblasts, endogenous histone deacetylase HDAC4 shuttles between
      cytoplasmic and nuclear compartments, supporting the hypothesis that its
      subcellular localization is dynamically regulated. However, upon differentiation,
      this dynamic equilibrium is disturbed and we find that HDAC4 accumulates in the
      nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle
      differentiation. Consistent with the notion of regulation of HDAC4 intracellular
      trafficking, we reveal that HDAC4 contains a modular structure consisting of a C
      terminal autonomous nuclear export domain, which, in conjunction with an internal
      regulatory domain responsive to calcium/calmodulin-dependent protein kinase IV
      (CaMKIV), determines its subcellular localization. CaMKIV phosphorylates HDAC4 in
      vitro and promotes its nuclear-cytoplasmic shuttling in vivo. However, although
      14-3-3 binding of HDAC4 has been proposed to be important for its cytoplasmic
      retention, we find this interaction to be independent of CaMKIV. Rather, the
      HDAC4.14-3-3 complex exists in the nucleus and is required to confer CaMKIV
      responsiveness. Our results suggest that the subcellular localization of HDAC4 is
      regulated by sequential phosphorylation events. The first event is catalyzed by a
      yet to be identified protein kinase that promotes 14-3-3 binding, and the second
      event, involving protein kinases such as CaMKIV, leads to efficient nuclear
      export of the HDAC4.14-3-3 complex.

PMID- 11470792
TI  - Characterization and mechanism of action of a reactivating factor for
      adenosylcobalamin-dependent glycerol dehydratase.
AB  - Adenosylcobalamin-dependent glycerol dehydratase undergoes mechanism-based
      inactivation by its physiological substrate glycerol. We identified two genes
      (gdrAB) of Klebsiella pneumoniae for a glycerol dehydratase-reactivating factor
      (Tobimatsu, T., Kajiura, H., Yunoki, M., Azuma, M., and Toraya, T. (1999) J.
      Bacteriol. 181, 4110-4113). Recombinant GdrA and GdrB proteins formed a tight
      complex of (GdrA)(2)(GdrB)(2), which is a putative reactivating factor. The
      purified factor reactivated the glycerol-inactivated and O(2)-inactivated
      glycerol dehydratases as well as activated the enzyme-cyanocobalamin complex in
      vitro in the presence of ATP, Mg(2+), and adenosylcobalamin. The factor mediated
      the exchange of the enzyme-bound, adenine-lacking cobalamins for free, adenine
      containing cobalamins in the presence of ATP and Mg(2+) through intermediate
      formation of apoenzyme. The factor showed extremely low ATP-hydrolyzing activity
      and formed a tight complex with apoenzyme in the presence of ADP. Incubation of
      the enzyme-cyanocobalamin complex with the reactivating factor in the presence of
      ADP brought about release of the enzyme-bound cobalamin. The resulting tight
      inactive complex of apoenzyme with the factor dissociated upon incubation with
      ATP, forming functional apoenzyme and a low affinity form of factor. Thus, it was
      established that the reactivation of the inactivated holoenzymes takes place in
      two steps: ADP-dependent cobalamin release and ATP-dependent dissociation of the
      apoenzyme-factor complex. We propose that the glycerol dehydratase-reactivating
      factor is a molecular chaperone that participates in reactivation of the
      inactivated enzymes.

PMID- 11470793
TI  - Membrane topology of the murine fatty acid transport protein 1.
AB  - The murine fatty acid transport protein (FATP1) was identified in an expression
      cloning screen for proteins that facilitate transport of fatty acids across the
      plasma membranes of mammalian cells. Hydropathy analysis of this protein suggests
      a model in which FATP1 has multiple membrane-spanning domains. To test this
      model, we inserted a hemagglutinin epitope tag at the amino terminus or a FLAG
      tag at the carboxyl terminus of the FATP1 cDNA and expressed these constructs in
      NIH 3T3 cells. Both tagged constructs produce proteins of the expected molecular
      masses and are functional in fatty acid import assays. Indirect
      immunofluorescence studies with selective permeabilization conditions and
      protease protection studies of sealed membrane vesicles from cells expressing
      epitope-tagged FATP1 were performed. These experiments show that the extreme
      amino terminus of tagged FATP1 is oriented toward the extracellular space,
      whereas the carboxyl terminus faces the cytosol. Additionally, enhanced green
      fluorescent protein fusion constructs containing predicted membrane-associated or
      soluble portions of FATP1 were expressed in Cos7 cells and analyzed by
      immunofluorescence and subcellular fractionation. These experiments demonstrate
      that amino acids 1-51, 52-100, and 101-190 contain signals for integral
      association with the membrane, whereas residues 258-313 and 314-475 are only
      peripherally membrane-associated. Amino acid residues 191-257 and 476-646 do not
      direct membrane association and likely face the cytosol. Taken together, these
      data support a model of FATP1 as a polytopic membrane protein with at least one
      transmembrane and multiple membrane-associated domains. This study provides the
      first experimental evidence for topology of a member of the family of plasma
      membrane fatty acid transport proteins.

PMID- 11470794
TI  - Med9/Cse2 and Gal11 modules are required for transcriptional repression of
      distinct group of genes.
AB  - The yeast Mediator is composed of two subcomplexes, Rgr1 and Srb4, known to be
      required for diverse aspects of transcriptional regulation; however, their
      structural and functional organizations have not yet been deciphered in detail.
      Biochemical analyses designed to determine the subunit composition of the Rgr1
      subcomplex revealed that the regulator-interacting subcomplex has a modular
      structure and is composed of the Gal11, Med9/Cse2, and Med10/Nut2 modules. Genome
      wide gene expression and Northern analyses performed in the presence or absence
      of the various Mediator modules revealed a distinct requirement for the Gal11,
      Med9/Cse2, and Med10/Nut2 modules in transcriptional repression as well as
      activation. GST pull-down analysis revealed that the transcriptional repressor
      Tup1 binds to distinct but overlapping regions of the Gal11 module that were
      shown previously to be transcriptional activator binding sites. These data
      suggest that competition between transcriptional activators and repressors for a
      common binding site in the Mediator and distinct conformational changes in the
      Mediator induced by repressor binding may underlie the mechanism of
      transcriptional repression in eukaryotes.

PMID- 11470795
TI  - Reciprocal regulation of capacitative and arachidonate-regulated noncapacitative
      Ca2+ entry pathways.
AB  - Receptor-activated Ca(2+) entry is usually thought to occur via capacitative or
      store-operated Ca(2+) channels. However, at physiological levels of stimulation,
      where Ca(2+) store depletion is only transient and/or partial, evidence has
      suggested that an arachidonic acid-dependent noncapacitative Ca(2+) entry is
      responsible. Recently, we have described a novel arachidonate-regulated Ca(2+)
      selective (ARC) conductance that is entirely distinct from store-operated
      conductances in the same cell. We now show that these ARC channels are indeed
      specifically activated by low agonist concentrations and provide the predominant
      route of Ca(2+) entry under these conditions. We further demonstrate that
      sustained elevations in cytosolic Ca(2+), such as those resulting from activation
      of store-operated Ca(2+) entry by high agonist concentrations, inhibit the ARC
      channels. This explains earlier failures to detect the presence of this
      noncapacitative pathway in experiments where store-operated entry had already
      been fully activated. The result is that the respective activities of ARC and
      store-operated Ca(2+) channels display a unique reciprocal regulation that is
      related to the specific nature of the [Ca(2+)](i) signals generated at different
      agonist concentrations. Importantly, these data show that at physiologically
      relevant levels of stimulation, it is the noncapacitative ARC channels that
      provide the predominant route for the agonist-activated entry of Ca(2+).

PMID- 11470796
TI  - Sphingosine 1-phosphate and isoform-specific activation of phosphoinositide 3
      kinase beta. Evidence for divergence and convergence of receptor-regulated
      endothelial nitric-oxide synthase signaling pathways.
AB  - Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid that elicits
      diverse biological responses, including angiogenesis, via the activation of G
      protein-coupled EDG receptors. S1P activates the endothelial isoform of nitric
      oxide synthase (eNOS), associated with eNOS phosphorylation at Ser-1179, a site
      phosphorylated by protein kinase Akt. We explored the proximal signaling pathways
      that mediate Akt activation and eNOS regulation by S1P/EDG receptors. Akt is
      regulated by the lipid kinase phosphoinositide 3-kinase (PI3-K). We found that
      bovine aortic endothelial cells (BAEC) express both alpha and beta isoforms of
      PI3-K, while lacking the gamma isoform. S1P treatment led to the rapid and
      isoform-specific activation of PI3-Kbeta in BAEC. PI3-Kbeta can be regulated by G
      protein betagamma subunits (Gbetagamma). The overexpression of a peptide
      inhibitor of Gbetagamma attenuated S1P-induced eNOS enzyme activation, as well as
      S1P-induced phosphorylation of eNOS and Akt. In contrast, bradykinin, a classical
      eNOS agonist, neither activated any PI3-K isoform nor induced eNOS
      phosphorylation at Ser-1179, despite activating eNOS in BAEC. Vascular
      endothelial growth factor activated both PI3-Kalpha and PI3-Kbeta via tyrosine
      kinase pathways and promoted eNOS phosphorylation that was unaffected by
      Gbetagamma inhibition. These findings indicate that PI3-Kbeta (regulated by
      Gbetagamma) may represent a novel molecular locus for eNOS activation by EDG
      receptors in vascular endothelial cells. These studies also indicate that
      different eNOS agonists activate distinct signaling pathways that diverge
      proximally following receptor activation but converge distally to activate eNOS.

PMID- 11470797
TI  - Molecular cloning and characterization of a dermatan-specific N
      acetylgalactosamine 4-O-sulfotransferase.
AB  - We have identified and characterized an N-acetylgalactosamine-4-O
      sulfotransferase designated dermatan-4-sulfotransferase-1 (D4ST-1) (GenBank(TM)
      accession number AF401222) based on its homology to HNK-1 sulfotransferase. The
      cDNA predicts an open reading frame encoding a type II membrane protein of 376
      amino acids with a 43-amino acid cytoplasmic domain and a 316-amino acid luminal
      domain containing two potential N-linked glycosylation sites. D4ST-1 has
      significant amino acid identity with HNK-1 sulfotransferase (21.4%), N
      acetylgalactosamine-4-O-sulfotransferase 1 (GalNAc-4-ST1) (24.7%), N
      acetylgalactosamine-4-O-sulfotransferase 2 (GalNAc-4-ST2) (21.0%), chondroitin-4
      O-sulfotransferase 1 (27.3%), and chondroitin-4-O-sulfotransferase 2 (22.8%).
      D4ST-1 transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc that is
      substituted with an alpha-linked iduronic acid (IdoUA) at the C-3 hydroxyl. D4ST
      1 shows a strong preference in vitro for sulfate transfer to
      IdoUAalpha1,3GalNAcbeta1,4 that is flanked by GlcUAbeta1,3GalNAcbeta1,4 as
      compared with IdoUAalpha1,3GalNAcbeta1,4 flanked by IdoUAalpha1,3GalNAcbeta1,4.
      The specificity of D4ST-1 when assayed in vitro suggests that the addition of
      sulfate to GalNAc occurs immediately after epimerization of GlcUA to IdoUA. The
      open reading frame of D4ST-1 is encoded by a single exon located on human
      chromosome 15q14. Northern blot analysis reveals a single 2.4-kilobase
      transcript. D4ST-1 message is expressed in virtually all tissues at some level
      but is most highly expressed in pituitary, placenta, uterus, and thyroid. The
      properties of D4ST-1 indicate that sulfation of the GalNAc moieties in dermatan
      is mediated by a distinct GalNAc-4-O-sulfotransferase and occurs following
      epimerization of GlcUA to IdoUA.

PMID- 11470798
TI  - A 5' Leader of Rbm3, a Cold Stress-induced mRNA, Mediates Internal Initiation of
      Translation with Increased Efficiency under Conditions of Mild Hypothermia.
AB  - Although mild hypothermia generally reduces protein synthesis in mammalian cells,
      the expression of a small number of proteins, including Rbm3, is induced under
      these conditions. In this study, we identify an Rbm3 mRNA with a complex 5'
      leader sequence containing multiple upstream open reading frames. Although these
      are potentially inhibitory to translation, monocistronic reporter mRNAs
      containing this leader were translated relatively efficiently. In addition, when
      tested in the intercistronic region of dicistronic mRNAs, this leader
      dramatically enhanced second cistron translation, both in transfected cells and
      in cell-free lysates, suggesting that the Rbm3 leader mediates cap-independent
      translation via an internal ribosome entry site (IRES). Inasmuch as Rbm3 mRNA and
      protein levels are both increased in cells exposed to mild hypothermia, the
      activity of this IRES was evaluated at a cooler temperature. Compared to 37
      degrees C, IRES activity at 33 degrees C was enhanced up to 5-fold depending on
      the cell line. Moderate enhancements also occurred with constructs containing
      other viral and cellular IRESes. These effects of mild hypothermia on translation
      were not caused by decreased cell growth, as similar effects were not observed
      when cells were serum starved. The results suggest that cap-independent
      mechanisms may facilitate the translation of particular mRNAs during mild
      hypothermia.

PMID- 11470799
TI  - Calmodulin-dependent kinase II mediates T cell receptor/CD3- and phorbol ester
      induced activation of IkappaB kinase.
AB  - Numerous fundamental biological processes involve the NFkappaB family of
      transcription factors. The mechanisms by which this family of proteins is
      regulated are therefore of widespread importance. In most cells, NFkappaB is
      bound to inhibitory IkappaB proteins and sequestered in the cytoplasm. NFkappaB
      inducing signals result in activation of a large multisubunit kinase complex,
      IKK, which phosphorylates IkappaB. IkappaB is subsequently degraded, releasing
      NFkappaB, which translocates to the nucleus. We previously reported that
      inhibitors of the calcium-binding protein calmodulin (CaM) prevent phorbol ester
      induced phosphorylation of IkappaB. Here we show that KN93, an inhibitor of CaM
      dependent kinases (CaMKs), also inhibits the phosphorylation of IkappaB. The
      effect of both CaM and CaMK inhibitors on IkappaB phosphorylation is due to the
      inhibition of the activity of CaMK II because neither drug has any effect when a
      derivative of CaMK II that is insensitive to these inhibitors is expressed. When
      CaMK II is inhibited, phorbol ester is no longer able to activate IKK, placing
      CaMK II in the signaling pathway that leads to IKK activation. CaM and CaMK
      inhibitors also block T cell receptor/CD3-induced activation but have no effect
      on the ability of the cytokine tumor necrosis factor alpha or the phosphatase
      inhibitor calyculin A to induce degradation of IkappaB. Finally we show that
      expression of a constitutively active CaMK II results in the activation of
      NFkappaB. The results identify CaMK II as a mediator of IKK activation
      specifically in response to T cell receptor/CD3 and phorbol ester stimulation.

PMID- 11470800
TI  - Structure of the Rad50 x Mre11 DNA repair complex from Saccharomyces cerevisiae
      by electron microscopy.
AB  - The RAD50 gene of Saccharomyces cerevisiae is one of several genes required for
      recombinational repair of double-strand DNA breaks during vegetative growth and
      for initiation of meiotic recombination. Rad50 forms a complex with two other
      proteins, Mre11 and Xrs2, and this complex is involved in double-strand break
      formation and processing. Rad50 has limited sequence homology to the structural
      maintenance of chromosomes (SMC) family of proteins and shares the same domain
      structure as SMCs: N- and C-terminal globular domains separated by two long
      coiled-coils. However, a notable difference is the much smaller non-coil hinge
      region between the two coiled-coils. We report here a structural analysis of full
      length S. cerevisiae Rad50, alone and in a complex with yeast Mre11 by electron
      microscopy. Our results confirm that yeast Rad50 does have the same antiparallel
      coiled-coil structure as SMC proteins, but with no detectable globular hinge
      domain. However, the molecule is still able to bend sharply in the middle to
      bring the two catalytic domains together, indicating that the small hinge domain
      is flexible. We also demonstrate that Mre11 binds as a dimer between the
      catalytic domains of Rad50, bringing the nuclease activities of Mre11 in close
      proximity to the ATPase and DNA binding activities of Rad50.

PMID- 11470801
TI  - Identification of a novel kinesin-related protein, KRMP1, as a target for mitotic
      peptidyl-prolyl isomerase Pin1.
AB  - Mitosis utilizes a number of kinesin-related proteins (KRPs). Here we report the
      identification of a novel KRP termed KRMP1, which has a deduced 1780-amino acid
      sequence composed of ternary domains. The amino-terminal head domain is most
      similar to the kinesin motor domain of the MKLP-1 subfamily and has an intrinsic
      ATPase activity that is diminished by substituting the consensus Lys-168 with
      Arg. The central stalk domain is predicted to form a long alpha-helical coiled
      coil, and can interact with each other in vivo. An in vivo labeling experiment
      revealed that KRMP1 is phosphorylated, and we also found that the region within
      the tail domain containing Thr-1604 as the cdc2 kinase phosphorylation site
      differs from the bimC box conserved in the bimC subfamily of KRPs.
      Immunofluorescence analysis showed that endogenous KRMP1 was localized
      predominantly to the cytoplasm during interphase and dispersed throughout the
      cell during mitosis. Consistent with this finding, overexpressed KRMP1 was
      detected in a complicated nuclear or cytoplasmic pattern reflecting multiple
      nuclear localization/export signals. Furthermore, KRMP1 interacted with the
      mitotic peptidyl-prolyl isomerase Pin1 in vivo, and an in vitro interaction was
      detected between the tail domain of KRMP1 and the WW domain of Pin1.
      Overexpression of KRMP1 caused COS-7 cells to arrest at G(2)-M, and co-expression
      of Pin1 reversed this effect, indicating their physiological interaction.
      Together, our results suggest that KRMP1 is a mitotic target regulated by Pin1
      and vice versa.

PMID- 11470802
TI  - Mechanism of suppression of cytochrome P-450 1A1 expression by tumor necrosis
      factor-alpha and lipopolysaccharide.
AB  - Proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin
      1beta, and lipopolysaccharides (LPS), suppress the gene expression of cytochrome
      P-450 1A1 (cyp1a1). The mechanism of the suppression is not well understood. In
      present study, we show that activation of nuclear factor-kappaB (NF-kappaB) is a
      critical event leading to the suppression of cyp1a1 gene expression, thus
      providing an underlying mechanism for the TNF-alpha- and LPS-induced cyp1a1
      suppression. We demonstrated that: (i) inducible RelA expression down-regulated
      aryl hydrocarbon receptor (AhR) activated reporter gene; (ii) the suppressive
      effects of LPS and TNF-alpha on the AhR-activated reporter gene could be blocked
      by pyrrolidine dithiocarbamate, which is known to inhibit NF-kappaB action; and
      (iii) TNF-alpha and LPS-imposed repression could be reversed by the NF-kappaB
      super repressor (SRIkappaBalpha), thus demonstrating the specific involvement of
      NF-kappaB. Furthermore, nuclear receptor coactivators p300/CBP and steroid
      receptor coactivator-1 act individually as well as cooperatively to reverse the
      suppressive effects by NF-kappaB on the AhR-activated reporter gene, suggesting
      that these transcriptional coactivators serve as the common integrators for the
      two pathways, thereby mediating the cross-interactions between AhR and NF-kappaB.
      Finally, using the chromatin immunoprecipitation assay, we demonstrated that AhR
      ligand induces histone H4 acetylation at the cyp1a1 promoter region containing
      the TATA box, whereas TNF-alpha inhibits this acetylation, suggesting that AhR/NF
      kappaB interaction converges at level of transcription involving chromatin
      remodeling.

PMID- 11470803
TI  - Multiple interactions of auxilin 1 with clathrin and the AP-2 adaptor complex.
AB  - The removal of the clathrin coat is essential for vesicle fusion with acceptor
      membranes. Disassembly of the coat involves hsc70, which is specifically
      recruited by members of the auxilin protein family to clathrin lattices. In
      vitro, this function of auxilin does not require the globular amino-terminal
      domain of the clathrin heavy chain, which is known to play a prominent role in
      the interaction of clathrin with adaptors and numerous endocytic accessory
      proteins. Here we report the unexpected finding that the neuron-specific form of
      auxilin (auxilin 1) can also associate with the clathrin amino-terminal domain.
      This interaction is mediated through tandemly arranged sites within the auxilin 1
      carboxyl-terminal segment 547-910. The overlapping auxilin 1 fragments 547-714
      and 619-738 bind the clathrin terminal domain with high affinity, whereas auxilin
      1-(715-901) interacts only poorly with it. All three fragments also associate
      with the clathrin distal domain and the alpha-appendage domain of AP-2. Moreover,
      they support efficient assembly of clathrin triskelia into regular cages. A novel
      uncoating assay was developed to demonstrate that auxilin 1-(715-901) functions
      efficiently as a cofactor for hsc70 in the uncoating of clathrin-coated vesicles.
      The multiple protein-protein interactions of auxilin 1 suggest that its function
      in endocytic trafficking may be more complex than previously anticipated.

PMID- 11470804
TI  - Molecular identification and characterization of two medium-chain acyl-CoA
      synthetases, MACS1 and the Sa gene product.
AB  - In this study, we identified and characterized two murine cDNAs encoding medium
      chain acyl-CoA synthetase (MACS). One, designated MACS1, is a novel protein and
      the other the product of the Sa gene (Sa protein), which is preferentially
      expressed in spontaneously hypertensive rats. Based on the murine MACS1 sequence,
      we also identified the location and organization of the human MACS1 gene, showing
      that the human MACS1 and Sa genes are located in the opposite transcriptional
      direction within a 150-kilobase region on chromosome 16p13.1. Murine MACS1 and Sa
      protein were overexpressed in COS cells, purified to homogeneity, and
      characterized. Among C4-C16 fatty acids, MACS1 preferentially utilizes octanoate,
      whereas isobutyrate is the most preferred fatty acid among C2-C6 fatty acids for
      Sa protein. Like Sa gene transcript, MACS1 mRNA was detected mainly in the liver
      and kidney. Subcellular fractionation revealed that both MACS1 and Sa protein are
      localized in the mitochondrial matrix. (14)C-Fatty acid incorporation studies
      indicated that acyl-CoAs produced by MACS1 and Sa protein are utilized mainly for
      oxidation.

PMID- 11470814
TI  - Mystery solved: discovery of a novel integrin ligand in the developing kidney.
AB  - Mutant mice lacking the integrin alpha8 subunit exhibit variable defects in
      kidney development with most mutants missing both kidneys. Several lines of
      evidence indicate that the known extracellular matrix ligands for integrin
      alpha8beta1 are either dispensable for or not involved in alpha8beta1 signaling
      during kidney development. This suggests the presence of an unknown ligand. A
      novel alpha8beta1 ligand, nephronectin, has now been identified. Nephronectin is
      a new extracellular matrix protein associated with the Wolffian duct and the
      ureteric bud, epithelial structures with well-defined roles in kidney
      development.

PMID- 11470815
TI  - Mitosis, microtubules, and the matrix.
AB  - The mechanical events of mitosis depend on the action of microtubules and mitotic
      motors, but whether these spindle components act alone or in concert with a
      spindle matrix is an important question.

PMID- 11470816
TI  - Hsp90: a specialized but essential protein-folding tool.
AB  - Hsp90 is unique among molecular chaperones. The majority of its known substrates
      are signal transduction proteins, and recent work indicates that it uses a novel
      protein-folding strategy.

PMID- 11470817
TI  - Regulation of limb patterning by extracellular microfibrils.
AB  - To elucidate the contribution of the extracellular microfibril-elastic fiber
      network to vertebrate organogenesis, we generated fibrillin 2 (Fbn2)-null mice by
      gene targeting and identified a limb-patterning defect in the form of bilateral
      syndactyly. Digit fusion involves both soft and hard tissues, and is associated
      with reduced apoptosis at affected sites. Two lines of evidence suggest that
      syndactily is primarily due to defective mesenchyme differentiation, rather than
      reduced apoptosis of interdigital tissue. First, fusion occurs before appearance
      of interdigital cell death; second, interdigital tissues having incomplete
      separation fail to respond to apoptotic clues from implanted BMP-4 beads.
      Syndactyly is associated with a disorganized matrix, but with normal BMP gene
      expression. On the other hand, mice double heterozygous for null Fbn2 and Bmp7
      alleles display the combined digit phenotype of both nullizygotes. Together,
      these results imply functional interaction between Fbn2-rich microfibrils and BMP
      7 signaling. As such, they uncover an unexpected relationship between the
      insoluble matrix and soluble factors during limb patterning. We also demonstrate
      that the Fbn2- null mutation is allelic to the recessive shaker-with-syndactyly
      (sy) locus on chromosome 18.

PMID- 11470818
TI  - The replication timing program of the Chinese hamster beta-globin locus is
      established coincident with its repositioning near peripheral heterochromatin in
      early G1 phase.
AB  - We have examined the dynamics of nuclear repositioning and the establishment of a
      replication timing program for the actively transcribed dihydrofolate reductase
      (DHFR) locus and the silent beta-globin gene locus in Chinese hamster ovary
      cells. The DHFR locus was internally localized and replicated early, whereas the
      beta-globin locus was localized adjacent to the nuclear periphery and replicated
      during the middle of S phase, coincident with replication of peripheral
      heterochromatin. Nuclei were prepared from cells synchronized at various times
      during early G1 phase and stimulated to enter S phase by introduction into
      Xenopus egg extracts, and the timing of DHFR and beta-globin replication was
      evaluated in vitro. With nuclei isolated 1 h after mitosis, neither locus was
      preferentially replicated before the other. However, with nuclei isolated 2 or 3
      h after mitosis, there was a strong preference for replication of DHFR before
      beta-globin. Measurements of the distance of DHFR and beta-globin to the nuclear
      periphery revealed that the repositioning of the beta-globin locus adjacent to
      peripheral heterochromatin also took place between 1 and 2 h after mitosis. These
      results suggest that the CHO beta-globin locus acquires the replication timing
      program of peripheral heterochromatin upon association with the peripheral
      subnuclear compartment during early G1 phase.

PMID- 11470820
TI  - Targeting of an abundant cytosolic form of the protein import receptor at Toc159
      to the outer chloroplast membrane.
AB  - Chloroplast biogenesis requires the large-scale import of cytosolically
      synthesized precursor proteins. A trimeric translocon (Toc complex) containing
      two homologous GTP-binding proteins (atToc33 and atToc159) and a channel protein
      (atToc75) facilitates protein translocation across the outer envelope membrane.
      The mechanisms governing function and assembly of the Toc complex are not yet
      understood. This study demonstrates that atToc159 and its pea orthologue exist in
      an abundant, previously unrecognized soluble form, and partition between cytosol
      containing soluble fractions and the chloroplast outer membrane. We show that
      soluble atToc159 binds directly to the cytosolic domain of atToc33 in a homotypic
      interaction, contributing to the integration of atToc159 into the chloroplast
      outer membrane. The data suggest that the function of the Toc complex involves
      switching of atToc159 between a soluble and an integral membrane form.

PMID- 11470819
TI  - Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN,
      the spinal muscular atrophy gene product.
AB  - Cajal bodies (CBs) are nuclear suborganelles involved in the biogenesis of small
      nuclear ribonucleoproteins (snRNPs). In addition to snRNPs, they are highly
      enriched in basal transcription and cell cycle factors, the nucleolar proteins
      fibrillarin (Fb) and Nopp140 (Nopp), the survival motor neuron (SMN) protein
      complex, and the CB marker protein, p80 coilin. We report the generation of
      knockout mice lacking the COOH-terminal 487 amino acids of coilin. Northern and
      Western blot analyses demonstrate that we have successfully removed the full
      length coilin protein from the knockout animals. Some homozygous mutant animals
      are viable, but their numbers are reduced significantly when crossed to inbred
      backgrounds. Analysis of tissues and cell lines from mutant animals reveals the
      presence of extranucleolar foci that contain Fb and Nopp but not other typical
      nucleolar markers. These so-called "residual" CBs neither condense Sm proteins
      nor recruit members of the SMN protein complex. Transient expression of wild-type
      mouse coilin in knockout cells results in formation of CBs and restores these
      missing epitopes. Our data demonstrate that full-length coilin is essential for
      proper formation and/or maintenance of CBs and that recruitment of snRNP and SMN
      complex proteins to these nuclear subdomains requires sequences within the coilin
      COOH terminus.

PMID- 11470821
TI  - Golgi clusters and vesicles mediate mitotic inheritance independently of the
      endoplasmic reticulum.
AB  - We have examined the fate of Golgi membranes during mitotic inheritance in animal
      cells using four-dimensional fluorescence microscopy, serial section
      reconstruction of electron micrographs, and peroxidase cytochemistry to track the
      fate of a Golgi enzyme fused to horseradish peroxidase. All three approaches show
      that partitioning of Golgi membranes is mediated by Golgi clusters that persist
      throughout mitosis, together with shed vesicles that are often found associated
      with spindle microtubules. We have been unable to find evidence that Golgi
      membranes fuse during the later phases of mitosis with the endoplasmic reticulum
      (ER) as a strategy for Golgi partitioning (Zaal, K.J., C.L. Smith, R.S.
      Polishchuk, N. Altan, N.B. Cole, J. Ellenberg, K. Hirschberg, J.F. Presley, T.H.
      Roberts, E. Siggia, et al. 1999. Cell. 99:589-601) and suggest that these
      results, in part, are the consequence of slow or abortive folding of GFP-Golgi
      chimeras in the ER. Furthermore, we show that accurate partitioning is
      accomplished early in mitosis, by a process of cytoplasmic redistribution of
      Golgi fragments and vesicles yielding a balance of Golgi membranes on either side
      of the metaphase plate before cell division.

PMID- 11470822
TI  - Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces
      cerevisiae and interacts with the anaphase-promoting complex/cyclosome.
AB  - Adenovirus early region 4 open reading frame 4 (E4orf4) protein has been reported
      to induce p53-independent, protein phosphatase 2A (PP2A)-dependent apoptosis in
      transformed mammalian cells. In this report, we show that E4orf4 induces an
      irreversible growth arrest in Saccharomyces cerevisiae at the G2/M phase of the
      cell cycle. Growth inhibition requires the presence of yeast PP2A-Cdc55, and is
      accompanied by accumulation of reactive oxygen species. E4orf4 expression is
      synthetically lethal with mutants defective in mitosis, including Cdc28/Cdk1 and
      anaphase-promoting complex/cyclosome (APC/C) mutants. Although APC/C activity is
      inhibited in the presence of E4orf4, Cdc28/Cdk1 is activated and partially
      counteracts the E4orf4-induced cell cycle arrest. The E4orf4-PP2A complex
      physically interacts with the APC/C, suggesting that E4orf4 functions by directly
      targeting PP2A to the APC/C, thereby leading to its inactivation. Finally, we
      show that E4orf4 can induce G2/M arrest in mammalian cells before apoptosis,
      indicating that E4orf4-induced events in yeast and mammalian cells are highly
      conserved.

PMID- 11470823
TI  - Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret
      receptor tyrosine kinase and mediate neuronal differentiation.
AB  - Docking proteins are substrates of tyrosine kinases and function in the
      recruitment and assembly of specific signal transduction molecules. Here we found
      that p62dok family members act as substrates for the c-Ret receptor tyrosine
      kinase. In addition to dok-1, dok-2, and dok-3, we identified two new family
      members, dok-4 and dok-5, that can directly associate with Y1062 of c-Ret. Dok-4
      and dok-5 constitute a subgroup of dok family members that is coexpressed with c
      Ret in various neuronal tissues. Activated c-Ret promotes neurite outgrowth of
      PC12 cells; for this activity, Y1062 in c-Ret is essential. c-Ret/dok fusion
      proteins, in which Y1062 of c-Ret is deleted and replaced by the sequences of dok
      4 or dok-5, induce ligand-dependent axonal outgrowth of PC12 cells, whereas a c
      Ret fusion containing dok-2 sequences does not elicit this response. Dok-4 and
      dok-5 do not associate with rasGAP or Nck, in contrast to p62dok and dok-2.
      Moreover, dok-4 and dok-5 enhance c-Ret-dependent activation of mitogen-activated
      protein kinase. Thus, we have identified a subclass of p62dok proteins that are
      putative links with downstream effectors of c-Ret in neuronal differentiation.

PMID- 11470824
TI  - Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal
      activity.
AB  - Phosphatidylinositol 4,5-biphosphate (PIP2) has been implicated in a variety of
      cellular processes, including synaptic vesicle recycling. However, little is
      known about the spatial distribution of this phospholipid in neurons and its
      dynamics. In this study, we have focused on these questions by transiently
      expressing the phospholipase C (PLC)-delta1 pleckstrin homology (PH) domain fused
      to green fluorescent protein (GFP) in cultured hippocampal neurons. This PH
      domain binds specifically and with high affinity to PIP2. Live confocal imaging
      revealed that in resting cells, PH-GFP is localized predominantly on the plasma
      membrane. Interestingly, no association of PH-GFP with synaptic vesicles in
      quiescent neurons was observed, indicating the absence of detectable PIP2 on
      mature synaptic vesicles. Electrical stimulation of hippocampal neurons resulted
      in a decrease of the PH-GFP signal at the plasma membrane, most probably due to a
      PLC-mediated hydrolysis of PIP2. This was accompanied in the majority of
      presynaptic terminals by a marked increase in the cytoplasmic PH-GFP signal,
      localized most probably on freshly endocytosed membranes. Further investigation
      revealed that the increase in PH-GFP signal was dependent on the activation of N
      methyl-D-aspartate receptors and the consequent production of nitric oxide (NO).
      Thus, PIP2 in the presynaptic terminal appears to be regulated by postsynaptic
      activity via a retrograde action of NO.

PMID- 11470825
TI  - Vitamin D(3) promotes the differentiation of colon carcinoma cells by the
      induction of E-cadherin and the inhibition of beta-catenin signaling.
AB  - The beta-catenin signaling pathway is deregulated in nearly all colon cancers.
      Nonhypercalcemic vitamin D3 (1alpha,25-dehydroxyvitamin D(3)) analogues are
      candidate drugs to treat this neoplasia. We show that these compounds promote the
      differentiation of human colon carcinoma SW480 cells expressing vitamin D
      receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or
      metastasic derivative (SW620) cells lacking VDR. 1alpha,25(OH)2D(3) induced the
      expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens
      [ZO]-1, ZO-2, vinculin) and promoted the translocation of beta-catenin,
      plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated
      VDR competed with T cell transcription factor (TCF)-4 for beta-catenin binding.
      Accordingly, 1alpha,25(OH)2D(3) repressed beta-catenin-TCF-4 transcriptional
      activity. Moreover, VDR activity was enhanced by ectopic beta-catenin and reduced
      by TCF-4. Also, 1alpha,25(OH)2D(3) inhibited expression of beta-catenin-TCF-4
      responsive genes, c-myc, peroxisome proliferator-activated receptor delta, Tcf-1,
      and CD44, whereas it induced expression of ZO-1. Our results show that
      1alpha,25(OH)2D(3) induces E-cadherin and modulates beta-catenin-TCF-4 target
      genes in a manner opposite to that of beta-catenin, promoting the differentiation
      of colon carcinoma cells.

PMID- 11470826
TI  - Vaccinia virus utilizes microtubules for movement to the cell surface.
AB  - Vaccinia virus (VV) egress has been studied using confocal, video, and electron
      microscopy. Previously, intracellular-enveloped virus (IEV) particles were
      proposed to induce the polymerization of actin tails, which propel IEV particles
      to the cell surface. However, data presented support an alternative model in
      which microtubules transport virions to the cell surface and actin tails form
      beneath cell-associated enveloped virus (CEV) particles at the cell surface.
      Thus, VV is unique in using both microtubules and actin filaments for egress. The
      following data support this proposal. (a) Microscopy detected actin tails at the
      surface but not the center of cells. (b) VV mutants lacking the A33R, A34R, or
      A36R proteins are unable to induce actin tail formation but produce CEV and
      extracellular-enveloped virus. (c) CEV formation is inhibited by nocodazole but
      not cytochalasin D or 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3,4
      d)pyrimidine (PP1). (d) IEV particles tagged with the enhanced green fluorescent
      protein fused to the VV B5R protein moved inside cells at 60 microm/min. This
      movement was stop-start, was along defined pathways, and was inhibited reversibly
      by nocodazole. This velocity was 20-fold greater than VV movement on actin tails
      and consonant with the rate of movement of organelles along microtubules.

PMID- 11470827
TI  - MUP-4 is a novel transmembrane protein with functions in epithelial cell adhesion
      in Caenorhabditis elegans.
AB  - Tissue functions and mechanical coupling of cells must be integrated throughout
      development. A striking example of this coupling is the interactions of body wall
      muscle and hypodermal cells in Caenorhabditis elegans. These tissues are
      intimately associated in development and their interactions generate structures
      that provide a continuous mechanical link to transmit muscle forces across the
      hypodermis to the cuticle. Previously, we established that mup-4 is essential in
      embryonic epithelial (hypodermal) morphogenesis and maintenance of muscle
      position. Here, we report that mup-4 encodes a novel transmembrane protein that
      is required for attachments between the apical epithelial surface and the
      cuticular matrix. Its extracellular domain includes epidermal growth factor-like
      repeats, a von Willebrand factor A domain, and two sea urchin enterokinase
      modules. Its intracellular domain is homologous to filaggrin, an intermediate
      filament (IF)-associated protein that regulates IF compaction and that has not
      previously been reported as part of a junctional complex. MUP-4 colocalizes with
      epithelial hemidesmosomes overlying body wall muscles, beginning at the time of
      embryonic cuticle maturation, as well as with other sites of mechanical coupling.
      These findings support that MUP-4 is a junctional protein that functions in IF
      tethering, cell-matrix adherence, and mechanical coupling of tissues.

PMID- 11470828
TI  - mua-3, a gene required for mechanical tissue integrity in Caenorhabditis elegans,
      encodes a novel transmembrane protein of epithelial attachment complexes.
AB  - Normal locomotion of the nematode Caenorhabditis elegans requires transmission of
      contractile force through a series of mechanical linkages from the myofibrillar
      lattice of the body wall muscles, across an intervening extracellular matrix and
      epithelium (the hypodermis) to the cuticle. Mutations in mua-3 cause a separation
      of the hypodermis from the cuticle, suggesting this gene is required for
      maintaining hypodermal-cuticle attachment as the animal grows in size
      postembryonically. mua-3 encodes a predicted 3,767 amino acid protein with a
      large extracellular domain, a single transmembrane helix, and a smaller
      cytoplasmic domain. The extracellular domain contains four distinct protein
      modules: 5 low density lipoprotein type A, 52 epidermal growth factor, 1 von
      Willebrand factor A, and 2 sea urchin-enterokinase-agrin modules. MUA-3 localizes
      to the hypodermal hemidesmosomes and to other sites of mechanically robust
      transepithelial attachments, including the rectum, vulva, mechanosensory neurons,
      and excretory duct/pore. In addition, it is shown that MUA-3 colocalizes with
      cytoplasmic intermediate filaments (IFs) at these sites. Thus, MUA-3 appears to
      be a protein that links the IF cytoskeleton of nematode epithelia to the cuticle
      at sites of mechanical stress.

PMID- 11470829
TI  - Sodium channel beta1 and beta3 subunits associate with neurofascin through their
      extracellular immunoglobulin-like domain.
AB  - Sequence homology predicts that the extracellular domain of the sodium channel
      beta1 subunit forms an immunoglobulin (Ig) fold and functions as a cell adhesion
      molecule. We show here that beta1 subunits associate with neurofascin, a neuronal
      cell adhesion molecule that plays a key role in the assembly of nodes of Ranvier.
      The first Ig-like domain and second fibronectin type III-like domain of
      neurofascin mediate the interaction with the extracellular Ig-like domain of
      beta1, confirming the proposed function of this domain as a cell adhesion
      molecule. beta1 subunits localize to nodes of Ranvier with neurofascin in sciatic
      nerve axons, and beta1 and neurofascin are associated as early as postnatal day
      5, during the period that nodes of Ranvier are forming. This association of beta1
      subunit extracellular domains with neurofascin in developing axons may facilitate
      recruitment and concentration of sodium channel complexes at nodes of Ranvier.

PMID- 11470830
TI  - A stoichiometric complex of neurexins and dystroglycan in brain.
AB  - In nonneuronal cells, the cell surface protein dystroglycan links the
      intracellular cytoskeleton (via dystrophin or utrophin) to the extracellular
      matrix (via laminin, agrin, or perlecan). Impairment of this linkage is
      instrumental in the pathogenesis of muscular dystrophies. In brain, dystroglycan
      and dystrophin are expressed on neurons and astrocytes, and some muscular
      dystrophies cause cognitive dysfunction; however, no extracellular binding
      partner for neuronal dystroglycan is known. Regular components of the
      extracellular matrix, such as laminin, agrin, and perlecan, are not abundant in
      brain except in the perivascular space that is contacted by astrocytes but not by
      neurons, suggesting that other ligands for neuronal dystroglycan must exist. We
      have now identified alpha- and beta-neurexins, polymorphic neuron-specific cell
      surface proteins, as neuronal dystroglycan receptors. The extracellular sequences
      of alpha- and beta-neurexins are largely composed of laminin-neurexin-sex hormone
      binding globulin (LNS)/laminin G domains, which are also found in laminin, agrin,
      and perlecan, that are dystroglycan ligands. Dystroglycan binds specifically to a
      subset of the LNS domains of neurexins in a tight interaction that requires
      glycosylation of dystroglycan and is regulated by alternative splicing of
      neurexins. Neurexins are receptors for the excitatory neurotoxin alpha
      latrotoxin; this toxin competes with dystroglycan for binding, suggesting
      overlapping binding sites on neurexins for dystroglycan and alpha-latrotoxin. Our
      data indicate that dystroglycan is a physiological ligand for neurexins and that
      neurexins' tightly regulated interaction could mediate cell adhesion between
      brain cells.

PMID- 11470831
TI  - Identification and characterization of a novel extracellular matrix protein
      nephronectin that is associated with integrin alpha8beta1 in the embryonic
      kidney.
AB  - The epithelial-mesenchymal interactions required for kidney organogenesis are
      disrupted in mice lacking the integrin alpha8beta1. None of this integrin's known
      ligands, however, appears to account for this phenotype. To identify a more
      relevant ligand, a soluble integrin alpha8beta1 heterodimer fused to alkaline
      phosphatase (AP) has been used to probe blots and cDNA libraries. In newborn
      mouse kidney extracts, alpha8beta1-AP detects a novel ligand of 70-90 kD. This
      protein, named nephronectin, is an extracellular matrix protein with five EGF
      like repeats, a mucin region containing a RGD sequence, and a COOH-terminal MAM
      domain. Integrin alpha8beta1 and several additional RGD-binding integrins bind
      nephronectin. Nephronectin mRNA is expressed in the ureteric bud epithelium,
      whereas alpha8beta1 is expressed in the metanephric mesenchyme. Nephronectin is
      localized in the extracellular matrix in the same distribution as the ligand
      detected by alpha8beta1-AP and forms a complex with alpha8beta1 in vivo. Thus,
      these results strongly suggest that nephronectin is a relevant ligand mediating
      alpha8beta1 function in the kidney. Nephronectin is expressed at numerous sites
      outside the kidney, so it may also have wider roles in development. The
      approaches used here should be generally useful for characterizing the
      interactions of novel extracellular matrix proteins identified through genomic
      sequencing projects.

PMID- 11470832
TI  - Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF
      receptor.
AB  - Signaling through growth factor receptors controls such diverse cell functions as
      proliferation, migration, and differentiation. A critical question has been how
      the activation of these receptors is regulated. Most, if not all, of the known
      ligands for these receptors are soluble factors. However, as matrix components
      are highly tissue-specific and change during development and pathology, it has
      been suggested that select growth factor receptors might be stimulated by binding
      to matrix components. Herein, we describe a new class of ligand for the epidermal
      growth factor (EGF) receptor (EGFR) found within the EGF-like repeats of tenascin
      C, an antiadhesive matrix component present during organogenesis, development,
      and wound repair. Select EGF-like repeats of tenascin-C elicited mitogenesis and
      EGFR autophosphorylation in an EGFR-dependent manner. Micromolar concentrations
      of EGF-like repeats induced EGFR autophosphorylation and activated extracellular
      signal-regulated, mitogen-activated protein kinase to levels comparable to those
      induced by subsaturating levels of known EGFR ligands. EGFR-dependent adhesion
      was noted when the ligands were tethered to inert beads, simulating the
      physiologically relevant presentation of tenascin-C as hexabrachion, and
      suggesting an increase in avidity similar to that seen for integrin ligands upon
      surface binding. Specific binding to EGFR was further established by
      immunofluorescence detection of EGF-like repeats bound to cells and cross-linking
      of EGFR with the repeats. Both of these interactions were abolished upon
      competition by EGF and enhanced by dimerization of the EGF-like repeat. Such low
      affinity behavior would be expected for a matrix-"tethered" ligand; i.e., a
      ligand which acts from the matrix, presented continuously to cell surface EGF
      receptors, because it can neither diffuse away nor be internalized and degraded.
      These data identify a new class of "insoluble" growth factor ligands and a novel
      mode of activation for growth factor receptors.

PMID- 11470833
TI  - A novel approach to detecting and measuring recombination: new insights into
      evolution in viruses, bacteria, and mitochondria.
AB  - An accurate estimate of the extent of recombination is important whenever
      phylogenetic methods are applied to potentially recombining nucleotide sequences.
      Here, data sets from viruses, bacteria, and mitochondria were examined for
      deviations from clonality using a new approach for detecting and measuring
      recombination. The apparent rate heterogeneity (ARH) among sites in a sequence
      alignment can be inflated as an artifact of recombination. However, the
      composition of polymorphic sites will differ in a data set with recombination
      generated ARH versus a clonal data set that exhibits the equivalent degree of
      rate heterogeneity. This is because recombinant data sets, encompassing regions
      of conflicting phylogenetic history, tend to yield "starlike" trees that are
      superficially similar to those inferred from clonal data sets with weak
      phylogenetic signal throughout. Specifically, a recombinant data set will be
      unexpectedly rich in conflicting phylogenetic information compared with clonally
      generated data sets supporting the same tree shape. Its value of q-defined as the
      proportion of two-state parsimony-informative sites to all polymorphic sites-will
      be greater than that expected for nonrecombinant data. The method proposed here,
      the informative-sites test, compares the value of q against a null distribution
      of values found using Monte Carlo-simulated data evolved under the null
      hypothesis of clonality. A significant excess of q indicates that the assumption
      of clonality is not valid and hence that the ARH in the data is at least partly
      an artifact of recombination. Investigations of the procedure using simulated
      sequences indicated that it can successfully detect and measure recombination and
      that it is unlikely to produce "false positives." Simulations also showed that
      for recombinant data, naive use of maximum-likelihood models incorporating rate
      heterogeneity can lead to overestimation of the time to the most recent common
      ancestor. Application of the test to real data revealed for the first time that
      populations of viruses, like those of bacteria, can be brought close to complete
      linkage equilibrium by pervasive recombination. On the other hand, the test did
      not reject the hypothesis of clonality when applied to a data set from the coding
      region of human mitochondrial DNA, despite its high level of ARH and homoplasy.

PMID- 11470834
TI  - Secator: a program for inferring protein subfamilies from phylogenetic trees.
AB  - With the huge increase of protein data, an important problem is to estimate,
      within a large protein family, the number of sensible subsets for subsequent in
      depth structural, functional, and evolutionary analyses. To tackle this problem,
      we developed a new program, Secator, which implements the principle of an
      ascending hierarchical method using a distance matrix based on a multiple
      alignment of protein sequences. Dissimilarity values assigned to the nodes of a
      deduced phylogenetic tree are partitioned by a new stopping rule introduced to
      automatically determine the significant dissimilarity values. The quality of the
      clusters obtained by Secator is verified by a separate Jackknife study. The
      method is demonstrated on 24 large protein families covering a wide spectrum of
      structural and sequence conservation and its usefulness and accuracy with real
      biological data is illustrated on two well-studied protein families (the Sm
      proteins and the nuclear receptors).

PMID- 11470835
TI  - DNA diversity in sex-linked and autosomal genes of the plant species Silene
      latifolia and Silene dioica.
AB  - The relatively recent origin of sex chromosomes in the plant genus Silene
      provides an opportunity to study the early stages of sex chromosome evolution
      and, potentially, to test between the different population genetic processes
      likely to operate in nonrecombining chromosomes such as Y chromosomes. We
      previously reported much lower nucleotide polymorphism in a Y-linked gene (SlY1)
      of the plant Silene latifolia than in the homologous X-linked gene (SlX1). Here,
      we report a more extensive study of nucleotide diversity in these sex-linked
      genes, including a larger S. latifolia sample and a sample from the closely
      related species Silene dioica, and we also study the diversity of an autosomal
      gene, CCLS37.1. We demonstrate that nucleotide diversity in the Y-linked genes of
      both S. latifolia and S. dioica is very low compared with that of the X-linked
      gene. However, the autosomal gene also has low DNA polymorphism, which may be due
      to a selective sweep. We use a single individual of the related hermaphrodite
      species Silene conica, as an outgroup to show that the low SlY1 diversity is not
      due to a lower mutation rate than that for the X-linked gene. We also investigate
      several other possibilities for the low SlY1 diversity, including differential
      gene flow between the two species for Y-linked, X-linked, and autosomal genes.
      The frequency spectrum of nucleotide polymorphism on the Y chromosome deviates
      significantly from that expected under a selective-sweep model. However, we
      detect population subdivision in both S. latifolia and S. dioica, so it is not
      simple to test for selective sweeps. We also discuss the possibility that Y
      linked diversity is reduced due to highly variable male reproductive success, and
      we conclude that this explanation is unlikely.

PMID- 11470836
TI  - The evolutionary origins of eukaryotic protein disulfide isomerase domains: new
      evidence from the Amitochondriate protist Giardia lamblia.
AB  - A phylogenetic analysis of protein disulfide isomerase (PDI) domain evolution was
      performed with the inclusion of recently reported PDIs from the amitochondriate
      protist Giardia lamblia, yeast PDIs that contain a single thioredoxin-like
      domain, and PDIs from a diverse selection of protists. We additionally report and
      include two new giardial PDIs, each with a single thioredoxin-like domain.
      Inclusion of protist PDIs in our analyses revealed that the evolutionary history
      of the endoplasmic reticulum may not be simple. Phylogenetic analyses support
      common ancestry of all eukaryotic PDIs from a thioredoxin ancestor and
      independent duplications of thioredoxin-like domains within PDIs throughout
      eukaryote evolution. This was particularly evident for Acanthamoeba PDI,
      Dictyostelium PDI, and mammalian erp5 domains. In contrast, gene duplication,
      instead of domain duplication, produces PDI diversity in G. lamblia. Based on our
      results and the known diversity of PDIs, we present a new hypothesis that the
      five single-domain PDIs of G. lamblia may reflect an ancestral mechanism of
      protein folding in the eukaryotic endoplasmic reticulum. The PDI complement of G.
      lamblia and yeast suggests that a combination of PDIs may be used as a redox
      chain analogous to that known for bacterial Dsb proteins.

PMID- 11470837
TI  - Shared nucleotide composition biases among species and their impact on
      phylogenetic reconstructions of the Drosophilidae.
AB  - Compositional changes are a major feature of genome evolution. Overlooking
      nucleotide composition differences among sequences can seriously mislead
      phylogenetic reconstructions. Large compositional variation exists among the
      members of the family Drosophilidae. Until now, however, base composition
      differences have been largely neglected in the formulations of the nucleotide
      substitution process used to reconstruct the phylogeny of this important group of
      species. The present study adopts a maximum-likelihood framework of phylogenetic
      inference in order to analyze five nuclear gene regions and shows that (1) the
      pattern of compositional variation in the Drosophilidae does not match the
      phylogeny of the species; (2) accounting for the heterogeneous GC content with
      Galtier and Gouy's nucleotide substitution model leads to a tree that differs in
      significant aspects from the tree inferred when the nucleotide composition
      differences are ignored, even though both phylogenetic hypotheses attain strong
      nodal support in the bootstrap analyses; and (3) the LogDet distance correction
      cannot completely overcome the distorting effects of the compositional variation
      that exists among the species of the Drosophilidae. Our analyses confidently
      place the Chymomyza genus as an outgroup closer than the genus Scaptodrosophila
      to the Drosophila genus and conclusively support the monophyly of the Sophophora
      subgenus.

PMID- 11470838
TI  - CsRn1, a novel active retrotransposon in a parasitic trematode, Clonorchis
      sinensis, discloses a new phylogenetic clade of Ty3/gypsy-like LTR
      retrotransposons.
AB  - We screened the genome of a trematode, Clonorchis sinensis, in order to identify
      novel retrotransposons and thereby provide additional information on
      retrotransposons for comprehensive phylogenetic study. Considering the vast
      potential of retrotransposons to generate genetically variable regions among
      individual genomes, randomly amplified polymorphic DNAs (RAPDs) detected by
      arbitrarily primed polymerase chain reactions were selected as candidates for
      retrotransposon-related sequences. From RAPD analysis, we isolated and
      characterized a novel retrotransposon in C. sinensis as the first member of
      uncorrupted long-terminal-repeat (LTR) retrotransposons in phylum
      Platyhelminthes. The retrotransposon, which was named Clonorchis sinensis
      Retrotransposon 1 (CsRn1), showed a genomewide distribution and had a copy number
      of more than 100 per haploid genome. CsRn1 encoded an uninterrupted open reading
      frame (ORF) of 1,304 amino acids, and the deduced ORF exhibited similarities to
      the pol proteins of Ty3/gypsy-like LTR retrotransposons. The mobile activity of
      master copies was predicted by sequence analysis and confirmed by the presence of
      mRNA transcripts. Phylogenetic analysis of Ty3/gypsy-like LTR retrotransposons
      detected a new clade comprising CsRn1, Kabuki of Bombyx mori, and an
      uncharacterized element of Drosophila melanogaster. With its high repetitiveness
      and preserved mobile activity, it is proposed that CsRn1 may play a significant
      role in the genomic evolution of C. sinensis.

PMID- 11470839
TI  - Mitochondrial pseudogenes are pervasive and often insidious in the snapping
      shrimp genus Alpheus.
AB  - Here we show that multiple DNA sequences, similar to the mitochondrial cytochrome
      oxidase I (COI) gene, occur within single individuals in at least 10 species of
      the snapping shrimp genus Alpheus. Cloning of amplified products revealed the
      presence of copies that differed in length and (more frequently) in base
      substitutions. Although multiple copies were amplified in individual shrimp from
      total genomic DNA (gDNA), only one sequence was amplified from cDNA. These
      results are best explained by the presence of nonfunctional duplications of a
      portion of the mtDNA, probably located in the nuclear genome, since transfer into
      the nuclear gene would render the COI gene nonfunctional due to differences in
      the nuclear and mitochondrial genetic codes. Analysis of codon variation suggests
      that there have been 21 independent transfer events in the 10 species examined.
      Within a single animal, differences between the sequences of these pseudogenes
      ranged from 0.2% to 20.6%, and those between the real mtDNA and pseudogene
      sequences ranged from 0.2% to 18.8% (uncorrected). The large number of
      integration events and the large range of divergences between pseudogenes and
      mtDNA sequences suggest that genetic material has been repeatedly transferred
      from the mtDNA to the nuclear genome of snapping shrimp. Unrecognized pseudogenes
      in phylogenetic or population studies may result in spurious results, although
      previous estimates of rates of molecular evolution based on Alpheus sister taxa
      separated by the Isthmus of Panama appear to remain valid. Especially worrisome
      for researchers are those pseudogenes that are not obviously recognizable as
      such. An effective solution may be to amplify transcribed copies of protein
      coding mitochondrial genes from cDNA rather than using genomic DNA.

PMID- 11470840
TI  - DNA sequence variation in the mitochondrial control region of red-backed voles
      (Clethrionomys).
AB  - The complete mitochondrial DNA (mtDNA) control region was sequenced for 71
      individuals from five species of the rodent genus Clethrionomys both to
      understand patterns of variation and to explore the existence of previously
      described domains and other elements. Among species, the control region ranged
      from 942 to 971 bp in length. Our data were compatible with the proposal of three
      domains (extended terminal associated sequences [ETAS], central, conserved
      sequence blocks [CSB]) within the control region. The most conserved region in
      the control region was the central domain (12% of nucleotide positions variable),
      whereas in the ETAS and CSB domains, 22% and 40% of nucleotide positions were
      variable, respectively. Tandem repeats were encountered only in the ETAS domain
      of Clethrionomys rufocanus. This tandem repeat found in C. rufocanus was 24 bp in
      length and was located at the 5' end of the control region. Only two of the
      proposed CSB and ETAS elements appeared to be supported by our data; however, a
      "CSB1-like" element was also documented in the ETAS domain.

PMID- 11470841
TI  - Phylogenetic analyses of amino acid variation in the serpin proteins.
AB  - Phylogenetic analyses of 110 serpin protein sequences revealed clades consistent
      with independent phylogenetic analyses based on exon-intron structure and
      diagnostic amino acid sites. Trees were estimated by maximum likelihood, neighbor
      joining, and partial split decomposition using both the BLOSUM 62 and Jones
      Taylor-Thornton substitution matrices. Neighbor-joining trees gave results
      closest to those based on independent analyses using genomic and chromosomal
      data. The maximum-likelihood trees derived using the quartet puzzling algorithm
      were very conservative, producing many small clades that separated groups of
      proteins that other results suggest were related. Independent analyses based on
      exon-intron structure suggested that a neighbor-joining tree was more accurate
      than maximum-likelihood trees obtained using the quartet puzzling algorithm.

PMID- 11470842
TI  - Phylogenetic utility and evidence for multiple copies of elongation factor-1alpha
      in the spider genus Habronattus (Araneae: Salticidae).
AB  - In the continuing quest for informative genes for use in molecular systematics,
      the protein-coding gene Elongation factor-1alpha (EF-1alpha) has rapidly become
      one of the most prevalent "single-copy" nuclear genes utilized, particularly in
      arthropods. This paper explores the molecular evolutionary dynamics and
      phylogenetic utility of EF-1alpha in the salticid spider genus Habronattus. As
      has been reported for other arthropod lineages, our studies indicate that
      multiple (two) copies of EF-1alpha exist in Habronattus. These copies differ in
      intron structure and thus in size, making it possible to easily separate PCR
      amplification products. We present data for an intronless EF-1alpha copy for
      three Habronattus species. The presence of nonsense mutations and generally
      elevated rates of amino acid change suggest that this copy is evolving under
      relaxed functional constraints in Habronattus. A larger taxon sample (50 species
      plus outgroups) is presented for an EF-1alpha copy that includes both intron and
      exon regions. Characteristics of both regions suggest that this is a functional,
      orthologous copy in the species sampled. Maximum-likelihood relative-rate
      comparisons show that exon third codon sites are evolving more than 100 times as
      fast as second codon sites in these sequences and that intron sites are evolving
      about twice as fast as exon third sites. In combination, the EF-1alpha data
      provide robust, species-level phylogenetic signal that is largely congruent with
      morphologically well supported areas of Habronattus phylogeny. The recovery of
      some novel clades, and the unexpected fragmentation of others, suggests areas
      requiring further phylogenetic attention.

PMID- 11470843
TI  - Soybean receptor-like protein kinase genes: paralogous divergence of a gene
      family.
AB  - Receptor-like protein kinases (RLKs) in plants play major roles in cellular
      processes and stress responses. Three soybean (Glycine max) orthologs of
      Arabidopsis thaliana RLK were isolated and designated GmRLK1, GmRLK2, and GmRLK3.
      GmRLK1, GmRLK2, and GmRLK3 are similar in sequence, with GmRLK2 and GmRLK3 being
      nearly identical. The deduced amino acid sequences of GmRLK1, GmRLK2, and GmRLK3
      possess characteristics of a transmembrane leucine-rich repeat RLK, AtCLV1. DNA
      fingerprinting and PCR analyses of a bacterial artificial chromosome library
      identified five GmRLK contigs (I-V): three for GmRLK1 (I, II, and V), one for
      GmRLK2 (III), and one for both GmRLK2 and GmRLK3 (IV). Phylogenetic analysis of
      the soybean RLKs together with other plant RLKs indicates that soybean and A.
      thaliana CLV1s generate a CLV1 branch, while soybean, A. thaliana, and rice RLKs
      generate an RLK branch. Thus, the AtCLV1 orthologs may have evolved later than
      the other pathogen-, environmental stress-, plant hormone-, and development
      associated RLKs. A common ancestral GmRLK gene may have duplicated to give rise
      to GmRLK1, GmRLK2, and GmRLK3, or GmRLK2 and GmRLK3 may have resulted from a
      recent duplication event(s). Several amino acid replacements in the kinase domain
      of GmRLK1 compared with those of GmRLK2 and GmRLK3 may reflect evolutionary
      divergence of individual family members.

PMID- 11470844
TI  - Sequences homologous to the hobo transposable element in E strains of Drosophila
      melanogaster.
AB  - Hobo is one of the three Drosophila melanogaster transposable elements, together
      with the P and I elements, that seem to have recently invaded the genome of this
      species. Surveys of the presence of hobo in strains from different geographical
      and temporal origins have shown that recently collected strains contain complete
      and deleted elements with high sequence similarity (H strains), but old strains
      lack hobo elements (E strains). Besides the canonical hobo sequences, both H and
      E strains show other poorly known hobo-related sequences. In the present work, we
      analyze the presence, cytogenetic location, and structure of some of these
      sequences in E strains of D. melanogaster. By in situ hybridization, we found
      that euchromatic hobo-related sequences were in fixed positions in all six E
      strains analyzed: 38C in the 2L arm; 42B and 55A in the 2R arm; 79E and 80B in
      the 3L arm; and 82C, 84C, and 84D in the 3R arm. Sequence comparison shows that
      some of the hobo-related sequences from Oregon-R and iso-1 strains are similar to
      the canonical hobo element, but their analysis reveals that they are
      substantially diverged and rearranged and cannot code for a functional
      transposase. Our results suggest that these ubiquitous hobo-homologous sequences
      are immobile and are distantly related to the modern hobo elements from D.
      melanogaster.

PMID- 11470845
TI  - Cone opsin genes of african cichlid fishes: tuning spectral sensitivity by
      differential gene expression.
AB  - Spectral tuning of visual pigments is typically accomplished through changes in
      opsin amino acid sequence. Within a given opsin class, changes at a few key sites
      control wavelength specificity. To investigate known differences in the visual
      pigment spectral sensitivity of the Lake Malawi cichlids, Metriaclima zebra (368,
      488, and 533 nm) and Dimidiochromis compressiceps (447, 536, and 569 nm), we
      sequenced cone opsin genes from these species as well as Labeotropheus
      fuelleborni and Oreochromis niloticus. These cichlids have five distinct classes
      of cone opsin genes, including two unique SWS-2 genes. Comparisons of the
      inferred amino acid sequences from the five cone opsin genes of M. zebra, D.
      compressiceps, and L. fuelleborni show the sequences to be nearly identical.
      Therefore, evolution of key opsin sites cannot explain the differences in visual
      pigment sensitivities. Real-time PCR demonstrates that different cichlid species
      express different subsets of the available cone opsin genes. Metriaclima zebra
      and L. fuelleborni express a complement of genes which give them UV-shifted
      visual pigments, while D. compressiceps expresses a different set to produce a
      red-shifted visual system. Thus, variations in cichlid spectral sensitivity have
      arisen through evolution of gene regulation, rather than through changes in opsin
      amino acid sequence.

PMID- 11470846
TI  - Foraminifera and Cercozoa are related in actin phylogeny: two orphans find a
      home?
AB  - In recent years, the increased sampling of protein-coding genes from diverse
      eukaryotes has revealed that many aspects of each gene tree are at odds with
      other phylogenies. This has led to the belief that each gene tree has unique
      strengths and weaknesses, suggesting that an accurate picture of eukaryotic
      relationships will be achieved only through comparative phylogeny using several
      different genes. To this end, actin genes were characterized from two genera of
      chlorarachniophytes, Chlorarachnion and Lotharella, and three species of the
      cercomonad flagellate Cercomonas: Phylogenetic trees including these new actin
      genes confirm the recently proposed relationship between chlorarachniophytes and
      cercomonads (Cercozoa) and, more importantly, also show a close relationship
      between Cercozoa and Foraminifera. Both of these are major eukaryotic groups
      encompassing extremely diverse organisms, yet there is no strong evidence for the
      evolutionary position of either from morphological or molecular data. The union
      of Cercozoa and Foraminifera suggested by actin phylogeny represents a novel step
      in the long process of determining the broad relationships between all major
      eukaryotic groups.

PMID- 11470847
TI  - A family of selfish minicircular chromosomes with jumbled chloroplast gene
      fragments from a dinoflagellate.
AB  - Chloroplast genes of several dinoflagellate species are located on unigenic DNA
      minicircular chromosomes. We have now completely sequenced five aberrant
      minicircular chromosomes from the dinoflagellate Heterocapsa triquetra. These
      probably nonfunctional DNA circles lack complete genes, with each being composed
      of several short fragments of two or three different chloroplast genes and a
      common conserved region with a tripartite 9G-9A-9G core like the putative
      replicon origin of functional single-gene circular chloroplast chromosomes. Their
      sequences imply that all five circles evolved by differential deletions and
      duplications from common ancestral circles bearing fragments of four genes: psbA,
      psbC, 16S rRNA, and 23S rRNA. It appears that recombination between separate
      unigenic chromosomes initially gave intermediate heterodimers, which were
      subsequently stabilized by deletions that included part or all of one putative
      replicon origin. We suggest that homologous recombination at the 9G-9A-9G core
      regions produced a psbA/psbC heterodimer which generated two distinct chimeric
      circles by differential deletions and duplications. A 23S/16S rRNA heterodimer
      more likely formed by illegitimate recombination between 16S and 23S rRNA genes.
      Homologous recombination between the 9G-9A-9G core regions of both heterodimers
      and additional differential deletions and duplications could then have yielded
      the other three circles. Near identity of the gene fragments and 9G-9A-9G cores,
      despite diverging adjacent regions, may be maintained by gene conversion. The
      conserved organization of the 9G-9A-9G cores alone favors the idea that they are
      replicon origins and suggests that they may enable the aberrant minicircles to
      parasitize the chloroplast's replication machinery as selfish circles.

PMID- 11470848
TI  - Diplopod hemocyanin sequence and the phylogenetic position of the Myriapoda.
AB  - Hemocyanins are copper-containing respiratory proteins of the Arthropoda that
      have so far been thoroughly investigated only in the Chelicerata and the
      Crustacea but have remained unstudied until now in the Myriapoda. Here we report
      the first sequence of a myriapod hemocyanin. The hemocyanin of Spirostreptus sp.
      (Diplopoda: Spirostreptidae) is composed of two distinct subunits that are
      arranged in a 6 x 6 native molecule. The cloned hemocyanin subunit cDNA codes of
      for a polypeptide of 653 amino acids (75.5 kDa) that includes a signal peptide of
      18 amino acids. The sequence closely resembles that of the chelicerate
      hemocyanins. Molecular phylogenetic analyses reject with high statistical
      confidence the integrity of the Tracheata (i.e., Myriapoda + Insecta) but give
      conflicting results on the position of the myriapod hemocyanin. While distance
      matrix and maximum-likelihood methods support a basal position of the
      Spirostreptus hemocyanin with respect to the other hemocyanins, parsimony
      analysis suggests a sister group relationship with the chelicerate hemocyanins.
      The latter topology is also supported by a unique shared deletion of an alpha
      helix. A common ancestry of Myriapoda and Chelicerata should be seriously
      considered.

PMID- 11470849
TI  - Phylogenetic relationships of class II fumarase genes from trichomonad species.
AB  - Class II fumarase sequences were obtained by polymerase chain reaction from five
      trichomonad species. All residues known to be highly conserved in this enzyme
      were present. Nuclear run-on assays showed that one of the two genes identified
      in Tritrichomonas foetus was expressed, whereas no fumarase transcripts were
      detected in the related species Trichomonas vaginalis. These findings corroborate
      previous biochemical data. Fumarase genes were also expressed in Monocercomonas
      sp. and Tetratrichomonas gallinarum but not in Pentatrichomonas hominis,
      Trichomonas gallinae, Trichomonas tenax, and Trichomitus batrachorum under the
      culture conditions used. Molecular trees inferred by likelihood methods reveal
      that trichomonad sequences have no affinity to described class II fumarase genes
      from other eukaryotes. The absence of functional mitochondria in protists such as
      trichomonads suggests that they diverged from other eukaryotes prior to the alpha
      proteobacterial symbiosis that led to mitochondria. Furthermore, they are basal
      to other eukaryotes in rRNA analyses. However, support for the early-branching
      status of trichomonads and other amitochondriate protists based on phylogenetic
      analyses of multiple data sets has been equivocal. Although the presence of
      hydrogenosomes suggests that trichomonads once had mitochondria, their class II
      iron-independent fumarase sequences differ markedly from those of other
      mitochondriate eukaryotes. All of the class II fumarase genes described from
      other eukaryotes are of apparent alpha-proteobacterial origin and hence a marker
      of mitochondrial evolution. In contrast, the class II fumarase from trichomonads
      emerges among other eubacterial homologs. This is intriguing evidence for an
      independent acquisition of these genes in trichomonads apart from the
      mitochondrial endosymbiosis event that gave rise to the form present in other
      eukaryotes. The ancestral trichomonad class II fumarase may represent a
      prokaryotic form that was replaced in other eukaryotes after the divergence of
      trichomonads with the movement of endosymbiont genes into the nucleus.
      Alternatively, it may have been acquired via a separate endosymbiotic event or
      lateral gene transfer.

PMID- 11470850
TI  - Accuracy and power of the likelihood ratio test in detecting adaptive molecular
      evolution.
AB  - The selective pressure at the protein level is usually measured by the
      nonsynonymous/synonymous rate ratio (omega = dN/dS), with omega < 1, omega = 1,
      and omega > 1 indicating purifying (or negative) selection, neutral evolution,
      and diversifying (or positive) selection, respectively. The omega ratio is
      commonly calculated as an average over sites. As every functional protein has
      some amino acid sites under selective constraints, averaging rates across sites
      leads to low power to detect positive selection. Recently developed models of
      codon substitution allow the omega ratio to vary among sites and appear to be
      powerful in detecting positive selection in empirical data analysis. In this
      study, we used computer simulation to investigate the accuracy and power of the
      likelihood ratio test (LRT) in detecting positive selection at amino acid sites.
      The test compares two nested models: one that allows for sites under positive
      selection (with omega > 1), and another that does not, with the chi2 distribution
      used for significance testing. We found that use of the chi(2) distribution makes
      the test conservative, especially when the data contain very short and highly
      similar sequences. Nevertheless, the LRT is powerful. Although the power can be
      low with only 5 or 6 sequences in the data, it was nearly 100% in data sets of 17
      sequences. Sequence length, sequence divergence, and the strength of positive
      selection also were found to affect the power of the LRT. The exact distribution
      assumed for the omega ratio over sites was found not to affect the effectiveness
      of the LRT.

PMID- 11470851
TI  - Different patterns of expansion/contraction during the evolution of an mtDNA
      simple repeat.

PMID- 11470852
TI  - A mammalian gene evolved from the integrase domain of an LTR retrotransposon.

PMID- 11470853
TI  - Sex-chromosomal differentiation and amelogenin genes in mammals.

PMID- 11470854
TI  - A major mitochondrial gene rearrangement among closely related species.

PMID- 11470856
TI  - Gonadotrophin receptor expression on human granulosa cells of low and normal
      responders to FSH.
AB  - The aim of this study was to determine if follicle stimulating hormone receptor
      and luteinizing hormone receptor (FSH-R and LH-R) expression is altered on
      granulosa cells (GC) of women with low oestradiol responses to FSH. Cells were
      obtained from mature follicles (>17 mm) following controlled ovarian stimulation.
      For comparison, chinese hamster ovary (CHO) cells transfected with FSH-R or LH-R
      were also assessed. FSH-R and LH-R expression were detected by flow cytometry.
      Receptors were labelled with FSH-R antibodies, or with excess FSH or human
      chorionic gonadotrophin (HCG) and anti-FSH or HCG antibodies, and compared to
      multiple controls. Receptor expression on GCs was more heterogeneous than on CHO
      cells. Gonadotrophin receptor levels on GCs were not correlated with the number
      of FSH ampoules administered or peak oestradiol response. Low and normal response
      groups were defined using a ratio of peak oestradiol/number of FSH ampoules. FSH
      receptor expression was not different on GCs from low and normal responders.
      However, LH-R expression was higher on GCs of low responders compared to those of
      normal responders (P = 0.04 ) suggesting a trend to more advanced luteinization.
      Access of hormone to follicles was not reduced in low responders. Thus,
      differences in gonadotrophin receptor expression, hormone binding, and access of
      hormones to follicles do not appear to account for low oestradiol responses to
      FSH.

PMID- 11470857
TI  - Expression of the cystic fibrosis transmembrane conductance regulator in rat
      spermatids: implication for the site of action of antispermatogenic agents.
AB  - To establish whether cystic fibrosis transmembrane conductance regulator (CFTR)
      is functionally expressed in the testis, we subjected spermatogenic cells from
      rat testes to analysis of CFTR mRNA, protein and channel activity. CFTR mRNA was
      detected in the testes of mature but not immature rats using reverse
      transcription-polymerase chain reaction analysis. Western blot analysis performed
      with a CFTR specific antibody revealed immunoreactivity in the membrane extract
      of spermatogenic cells. Immunohistochemical studies localized CFTR in round and
      elongated spermatids, but not in the fully developed spermatozoa. Using a whole
      cell patch clamp technique, we recorded an inward current activated by
      intracellular cAMP (100 micromol/l) in round spermatids. The current displayed a
      linear I / V relationship and was inhibited by diphenylamine-2-carboxylate (DPC),
      a chloride channel blocker. Transfection of the rat germ cell CFTR cDNA into
      human embryonic kidney (HEK) 293 cells caused the expression of a cAMP-activated
      chloride current with CFTR characteristics. The current was completely blocked by
      the antispermatogenic agents 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid,
      lonidamine (500 micromol/l) and 1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid,
      AF2785 (250 micromol/l). These results taken together provide evidence that CFTR
      is differentially expressed in spermatids during spermiogenesis. We speculate
      that CFTR may interact with aquaporin to bring about cytoplasmic volume
      contraction which is an essential feature of spermiogenesis.

PMID- 11470858
TI  - Mapping of seminal plasma proteins by two-dimensional gel electrophoresis in men
      with normal and impaired spermatogenesis.
AB  - The present study analyses differential polypeptide expression of seminal plasma
      from fertile and infertile men by two-dimensional gel electrophoresis.
      Optimization of solubilization of seminal plasma was obtained by using [3-(3
      (cholamidopropyl) dimethyl-ammonio)-1-propane sulphonate] and chaotropic agent
      mixture in lysis buffer before separation in immobilized pH gradient for
      isoelectric focusing. A two-dimensional map of seminal plasma from a fertile man
      allowed the detection of about 750 spots. Semi-preparative electrofocusing was
      performed. Analysis of tryptic fragments of two major spots by matrix-assisted
      laser desorption-ionization time-of-flight (MALDI-TOF) mass spectroscopy resulted
      in identification of prostatic acid phosphatase and prostate specific antigen.
      Three groups of spots and seven individual spots of isoelectric point from 4.6 to
      6.2 and mol. wt from 41 to 18 kDa disappeared in the two-dimensional maps of
      seminal plasma of vasectomized men (n = 4) and of a patient with bilateral
      anorchidy as compared to that of fertile men (n = 5). Some of these polypeptides
      were also absent in seminal plasma of patients with alterations of seminiferous
      tubules showing Sertoli cell-only syndrome characteristics (n = 4) and could be
      potential diagnostic markers of spermatogenesis impairment.

PMID- 11470859
TI  - Protein tyrosine kinase expression in the porcine ovary.
AB  - Various growth factor receptors contain intrinsic tyrosine kinase activity,
      indicating that protein tyrosine kinases (PTK) play an important role in signal
      transduction pathways for cell proliferation and differentiation. To identify
      oocyte-derived factors which control follicle cells as well as oocyte-controlling
      factors produced by follicle cells, we examined the expression of genes which
      contain the PTK domain in the porcine ovary, using a polymerase chain reaction
      based amplification technique with degenerate oligonucleotide primers that are
      specific to the PTK domain. Clones for the porcine homologues of platelet-derived
      growth factor receptor alpha (PDGFRalpha) and of insulin-like growth factor-I
      receptor (IGF-IR) were found during follicle growth both in oocytes and follicle
      cells. Clones for the porcine homologues of focal adhesion kinase (FAK), of c-kit
      and of fms-like tyrosine kinase (FLT)-3 were found only in oocytes. Moreover,
      after 24 h of in-vitro maturation of the cumulus-oocyte complexes, clones for the
      porcine homologues of FLT-1, of FLT-4, of Tie2 and of RYK in oocytes were
      observed. Immunohistochemical studies revealed the existence of PDGFRalpha,
      platelet-derived growth factor A (PDGFA), FAK and FLT3 in oocytes at various
      stages of folliculogenesis. These results suggest that fluctuations in the
      expression of these PTK genes may be involved in follicle growth and maturation.

PMID- 11470860
TI  - The ovulatory gonadotrophin surge stimulates cyclooxygenase expression and
      prostaglandin production by the monkey follicle.
AB  - Follicular prostaglandin concentrations increase following the gonadotrophin
      surge in domestic animals and rodents approximately 10 h before follicle rupture,
      suggesting a unifying role for prostaglandins in the timing of ovulation.
      However, little is known about prostaglandin production by the primate ovulatory
      follicle. In this study, adult female macaques received gonadotrophins to promote
      follicular development. Granulosa cells, follicular fluid, and ovaries were
      collected before (0 h) and 12, 24 or 36 h after administration of the ovulatory
      stimulus, human chorionic gonadotrophin (HCG). Cyclooxygenase (COX) isoform
      expression was assessed by reverse transcription-polymerase chain reaction and
      immunocytochemistry and follicular prostaglandin production was determined by
      enzyme immunoassay. COX-2 mRNA expression in granulosa cells was low at 0 h, rose
      50-fold by 12 h, and remained elevated through to 36 h. COX-2 immunostaining was
      present in granulosa cells after, but not before, exposure to HCG. COX-1 mRNA
      levels did not change during the periovulatory interval, and COX-1 immunostaining
      of granulosa cells was not detected. Follicular fluid prostaglandin (PG) E (2)
      and PGF (2alpha) concentrations were low through to 24 h but increased 100-fold
      at 36 h. The elevated follicular prostaglandin concentrations 4-16 h before the
      expected time of ovulation support the hypothesis that the time between the LH
      surge and increased follicular prostaglandins determines the length of the
      periovulatory period. Differences between the localization and timing of COX-2
      expression in monkey versus non-primate follicles suggest that the pattern of COX
      2 expression and activity has aspects unique to primates.

PMID- 11470861
TI  - Expression and regulation of growth-regulated oncogene alpha in human endometrial
      stromal cells.
AB  - Growth-regulated oncogene alpha (GROalpha), a potent chemoattractant for
      neutrophils, has previously been detected in the endometrial stromal cells (ESC)
      of human endometrium. In this study, the mRNA expression of GROalpha in the
      endometrium was evaluated by reverse transcription-polymerase chain reaction
      analysis, while the localization of GROalpha protein was studied by
      immunohistochemistry and the concentrations of GROalpha were measured using an
      enzyme-linked immunosorbent assay (ELISA). The effects of known modulators of
      endometrial function on the production of GROalpha by ESC were also examined by
      ELISA and Northern blot analysis. The expression of both GROalpha mRNA and
      GROalpha protein was detected in the cycling endometrium. GROalpha protein was
      localized mainly in the stroma, and endometrial tissues in the secretory phase
      contained higher amounts of GROalpha protein than did those in the proliferative
      phase. The production of GROalpha by ESC was enhanced by in-vitro
      decidualization. Lipopolysaccharide, tumour necrosis factor-alpha and interleukin
      1beta also stimulated the expression of GROalpha mRNA and protein by ESC. These
      results suggest that the production of GROalpha by ESC is regulated by ovarian
      steroid hormones as well as by inflammatory mediators. The modulation of GROalpha
      concentrations in the local environment may contribute to normal and pathological
      processes in the uterus by regulating leukocyte trafficking in the endometrium.

PMID- 11470862
TI  - Haptoglobin is present in human endometrium and shows elevated levels in the
      decidua during pregnancy.
AB  - Assuming that haptoglobin, by virtue of its immunomodulatory properties, could be
      a regulatory factor during reproduction, its presence in the human uterus was
      determined. Protein extracts from endometrial tissue samples of pregnant and non
      pregnant women were analysed by the immunoblot technique and the intensities of
      specific bands were quantified. Bands corresponding to haptoglobin were
      identified in tissue samples obtained from both sources. Protein, purified by
      high-performance liquid chromatography and monitored by Western blot analysis for
      its haptoglobin identity, was used for amino-terminal sequencing. Sequencing of
      the 42 kDa protein identified it as the beta chain of haptoglobin.
      Immunohistochemistry was used to corroborate the findings and to visualize the
      distribution of haptoglobin in the tissue. The intensity of the 42 kDa band
      derived from decidua graviditatis was significantly higher than the intensity of
      bands derived from non-pregnant endometrium in the proliferative phase (P < 0.01)
      and in the secretory phase (P < 0.05). Immunohistochemical staining with anti
      human haptoglobin antibody elicited strong signals in the decidua graviditatis
      and weaker signals in the normal endometrium, with the latter showing menstrual
      cycle-dependent variation. Moderate staining of stroma and a lack of staining of
      epithelium in the proliferative phase contrasted with the strong staining of
      stroma and moderate level of staining of epithelium observed in the secretory
      phase. Haptoglobin in the uterus may exert several functions such as the known
      binding of haemoglobin, but could also be involved in the multi-factorial
      mechanism protecting the fetus from a maternal allograft-like immune response.

PMID- 11470863
TI  - Nitric oxide induces extensive apoptosis in endometrial epithelial cells in the
      presence of progesterone: involvement of mitogen-activated protein kinase
      pathways.
AB  - During trophoblast invasion, luminal and glandular endometrial epithelial cells
      (EEC) have been found to undergo apoptosis through undetermined mechanisms. We
      postulate that nitric oxide (NO) and progesterone may mediate apoptosis in EEC
      because they are produced by trophoblasts at concentrations that can cause
      apoptosis in non-uterine cells. Using a cultured EEC line, RL95-2, we found that
      sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP), two
      commonly used NO-releasing agents, caused the death of EEC in a dose-dependent
      manner and progesterone markedly enhanced NO-induced cytotoxicity. Cells treated
      with NO/progesterone showed a significant increase in the percentage of condensed
      nuclei, as detected by DAPI staining, and in caspase-3 activity, indicating that
      these cells underwent apoptosis. Immunoblot analysis revealed that SNP/NO could
      activate extracellular signal-regulated kinase (ERK) and, to a lesser extent, p38
      mitogen-activated protein kinase (MAPK). While pretreatment with PD98059 (an ERK
      inhibitor) did not prevent cell death, the addition of SB203580 (a p38 MAPK
      inhibitor) effectively rescued the cells from NO/progesterone treatment.
      Moreover, SNP/NO-induced p38 MAPK activation was significantly up-regulated by
      progesterone. Our results demonstrate that NO and progesterone may
      synergistically activate p38 MAPK to induce apoptosis in EEC, a process that may
      facilitate implantation.

PMID- 11470864
TI  - Vascular endothelial growth factor and placenta growth factor concentrations in
      Down's syndrome and control pregnancies.
AB  - Vascular endothelial growth factor (VEGF) and placenta growth factor (PLGF) are
      considered to play important roles in angiogenesis and vascular permeability
      during placental development. Since trisomy 21 placentae show trophoblastic
      hypoplasia and hypovascularity, we investigated PLGF and VEGF synthesis in Down's
      syndrome pregnancies. Maternal serum was collected from 102 euploid and 24
      trisomy 21 pregnancies between 15 and 20 weeks gestation and tested for these two
      factors by enzyme-linked immunosorbent assays. Protein extracts from 15 normal
      and six trisomy 21 placentae were also tested. VEGF was not detected in maternal
      serum, while PLGF increased significantly with gestational age. Serum PLGF,
      transformed as a multiple of the gestational age median (MoM), in Down's syndrome
      pregnancies was significantly lower than in euploid controls (mean 0.67 +/- 0.043
      MoM versus 1.00 +/- 0.047 MoM, analysis of variance F = 11.605, P < 0.001 ). Both
      VEGF and PLGF were detected in placental protein extracts without variation
      according to gestational age. Down's syndrome placentae had significantly less
      PLGF compared to normal placentae (Mann-Whitney, P < 0.05 ) but no difference was
      observed in placental VEGF content (Mann-Whitney, P = 0.94 ). Considering the
      biological properties of PLGF, this decrease may provide new insights into the
      mechanism(s) leading to the structural and functional anomalies described in
      trisomy 21 placentae.

PMID- 11470865
TI  - In-vitro evidence of autocrine secretion of vascular endothelial growth factor by
      endothelial cells from human placental blood vessels.
AB  - Vascular endothelial growth factor (VEGF), a highly specific mitogen for vascular
      endothelial cells, is involved in placental vascular growth and remodelling. The
      aim of this study was to investigate whether placental endothelial cells secrete
      VEGF in an autocrine manner and if this secretion is correlated with endothelial
      cell growth. Blood vessels, excised from the apical surface of three human
      placentae, were sectioned into 40 fragments per placenta and cultured in fibrin
      gel matrix for 27 days. Immunohistochemical detection of placental endothelial
      cells was performed by positive staining with anti-human factor VIII-associated
      antigen and negative staining with anti-human alpha-actin and desmin. To
      investigate the production and autocrine action of VEGF, VEGF concentrations in
      culture media were measured and the effect of an anti-VEGF neutralizing antibody
      on endothelial cell growth was observed. The results demonstrate that soluble
      VEGF is secreted by placental endothelial cells reaching a plateau from day 24
      (68.74 +/- 7.52 pg/ml) to day 27 (67.20 +/- 6.28 pg/ml). Furthermore, VEGF
      concentrations in media collected on days 6, 12, 18, 21 and 27 of culture were
      found to be directly correlated to the sprouting parameter of endothelial cells,
      as calculated by image analysis on the same day ( P < 0.001, r (2) = 0.95 ). The
      use of 10 and 100 ng/ml of a neutralizing antibody against human VEGF suppressed
      cell proliferation, compared to that observed in the untreated controls, by 74.8
      +/- 7.3 and 89.4 +/- 3.9% respectively. In conclusion, this study reports the
      first evidence of autocrine secretion of VEGF by human placental endothelial
      cells and demonstrates the involvement of VEGF in endothelial cell growth within
      a fibrin gel culture.

PMID- 11470866
TI  - NAD(P)H oxidase in human fetal membrane chorion laeve trophoblasts with or
      without chorioamnionitis: ultrastructural enzyme histochemical study.
AB  - We examined the subcellular localizations of NAD(P)H oxidase, a reactive oxygen
      species (ROS)-producing enzyme, in fetal membrane chorion laeve trophoblasts from
      preterm or term pregnant women with or without chorioamnionitis (CAM).
      Ultrastructural enzyme histochemistry for NAD(P)H oxidase was used. In fetal
      membranes without CAM, approximately one quarter of the chorion laeve
      trophoblasts (25.6%) showed NAD(P)H oxidase activity on their surface plasma
      membranes and microvillous membranes. In mild CAM, the proportion of these
      NAD(P)H oxidase-positive cells significantly increased, reaching about half
      (51.0%). Enzyme activity appeared on the plasma and microvillous membranes and
      also on both phagosomal membranes and intracellular vesico-tubular structures.
      Appearance of NAD(P)H oxidase on surface plasma membranes, phagosomal membranes,
      and vesico-tubular structures is strong cytochemical evidence of phagocytic cell
      activation. These observations indicate that chorion laeve trophoblasts possess
      NAD(P)H oxidase activity, and therefore that fetal membranes themselves have ROS
      generating capacity. Further, in fetal membrane inflammation, chorion laeve
      trophoblasts exhibited enzyme distribution characteristic of activated
      professional phagocytes. Similar to phagocytes infiltrating to the intrauterine
      environment, chorion laeve trophoblast NAD(P)H oxidase may play a role both in
      the defence of chorioamnion against infection and in the pathogenesis or
      pathophysiology of CAM-related preterm delivery.

PMID- 11470867
TI  - Nuclear factor-kappa B is essential for up-regulation of interleukin-8 expression
      in human amnion and cervical epithelial cells.
AB  - Interleukin-8 (IL-8) is a cytokine which recruits and activates neutrophils into
      tissue stroma. It is present in uterine tissues and its concentration increases
      in the third trimester and with labour. The promoter region of the IL-8 gene
      contains binding sites for the transcription factors, nuclear factor-kappa B (NF
      kappaB), activator protein-1 (AP-1) and CCAAT/enhancer-binding protein (C/EBP).
      These are in close proximity to each other and to the coding region of the gene.
      This study used site-directed mutagenesis of each of these sites to examine the
      relative importance of each site in IL-8 gene expression in a cervical cell line
      and in amnion cells obtained before and after labour. We found that the NF-kappaB
      site was essential for basal and IL-1beta-stimulated gene expression in all cell
      types. Neither of the other binding sites was consistently essential for gene
      expression but may have an additive role in promoter activity. We conclude that
      the NF-kappaB binding site is essential for up-regulation of IL-8 gene expression
      in these uterine cell types. An increase in IL-8 expression has been shown to
      occur in the uterus in association with parturition and NF-kappaB binding to the
      promoter may be of importance at this time.

PMID- 11470869
TI  - The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein.
AB  - The product of the retinoblastoma susceptibility gene, the Rb protein, functions
      partly through transcriptional repression of E2F-regulated genes. Repression by
      Rb is mediated, at least in part, by a histone deacetylase complex, whose
      enzymatic activity relies on HDAC1, HDAC2 or HDAC3. Recently, we have shown that
      the Rb-associated histone deacetylase complex contains RbAp48 protein, which
      interacts with HDAC1 and HDAC2. RbAp48 could favour the deacetylation of histones
      since it binds directly to histone H4. In agreement with that, we show that
      transcriptional repression of E2F activity requires the presence of RbAp48. HDAC3
      was thought not to interact with RbAp48. However, we found that it shared with
      HDAC1 the ability to favour the recruitment of RbAp48 to Rb. This latter effect
      was unlikely to be due to activation of Rb function, since HDAC3 did not increase
      Rb-E2F1 interaction. Rather, we found, surprisingly, that HDAC3 could physically
      interact with RbAp48 both in vitro and in living cells. Taken together, our data
      suggest a model in which Rb mediates the recruitment to E2F-regulating promoters
      of a repressive complex containing either HDAC1, HDAC2 or HDAC3 and the histone
      binding protein RbAp48.

PMID- 11470870
TI  - Changing the target base specificity of the EcoRV DNA methyltransferase by
      rational de novo protein-design.
AB  - The EcoRV DNA-(adenine-N(6))-methyltransferase (M.EcoRV) specifically modifies
      the first adenine residue within GATATC sequences. During catalysis, the enzyme
      flips its target base out of the DNA helix and binds it into a target base
      binding pocket which is formed in part by Lys16 and Tyr196. A cytosine residue is
      accepted by wild-type M.EcoRV as a substrate at a 31-fold reduced efficiency with
      respect to the k(cat)/K(M) values if it is located in a CT mismatch substrate
      (GCTATC/GATATC). Cytosine residues positioned in a CG base pair (GCTATC/GATAGC)
      are modified at much more reduced rates, because flipping out the target base is
      much more difficult in this case. We intended to change the target base
      specificity of M.EcoRV from adenine-N(6) to cytosine-N(4). To this end we
      generated, purified and characterized 15 variants of the enzyme, containing
      single, double and triple amino acid exchanges following different design
      approaches. One concept was to reduce the size of the target base binding pocket
      by site-directed mutagenesis. The K16R variant showed an altered specificity,
      with a 22-fold preference for cytosine as the target base in a mismatch
      substrate. This corresponds to a 680-fold change in specificity, which was
      accompanied by only a small loss in catalytic activity with the cytosine
      substrate. The K16R/Y196W variant no longer methylated adenine residues at all
      and its activity towards cytosine was reduced only 17-fold. Therefore, we have
      changed the target base specificity of M.EcoRV from adenine to cytosine by
      rational protein design. Because there are no natural paragons for the variants
      described here, a change of the target base specificity of a DNA interacting
      enzyme was possible by rational de novo design of its active site.

PMID- 11470871
TI  - Bulged residues promote the progression of a loop-loop interaction to a stable
      and inhibitory antisense-target RNA complex.
AB  - In several groups of bacterial plasmids, antisense RNAs regulate copy number
      through inhibition of replication initiator protein synthesis. These RNAs are
      characterized by a long hairpin structure interrupted by several unpaired
      residues or bulged loops. In plasmid R1, the inhibitory complex between the
      antisense RNA (CopA) and its target mRNA (CopT) is characterized by a four-way
      junction structure and a side-by-side helical alignment. This topology
      facilitates the formation of a stabilizer intermolecular helix between distal
      regions of both RNAs, essential for in vivo control. The bulged residues in
      CopA/CopT were shown to be required for high in vitro binding rate and in vivo
      activity. This study addresses the question of why removal of bulged nucleotides
      blocks stable complex formation. Structure mapping, modification interference,
      and molecular modeling of bulged-less mutant CopA-CopT complexes suggests that,
      subsequent to loop-loop contact, helix propagation is prevented. Instead, a fully
      base paired loop-loop interaction is formed, inducing a continuous stacking of
      three helices. Consequently, the stabilizer helix cannot be formed, and stable
      complex formation is blocked. In contrast to the four-way junction topology, the
      loop-loop interaction alone failed to prevent ribosome binding at its loading
      site and, thus, inhibition of RepA translation was alleviated.

PMID- 11470872
TI  - Reverse transcriptase incorporation of 1,5-anhydrohexitol nucleotides.
AB  - Several reverse transcriptases were studied for their ability to accept
      anhydrohexitol triphosphates, having a conformationally restricted six-membered
      ring, as substrate for template-directed synthesis of HNA. It was found that AMV,
      M-MLV, M-MLV (H(-)), RAV2 and HIV-1 reverse transcriptases were able to recognise
      the anhydrohexitol triphosphate as substrate and to efficiently catalyse the
      incorporation of one non-natural anhydrohexitol nucleotide opposite a natural
      complementary nucleotide. However, only the dimeric enzymes, the RAV2 and HIV-1
      reverse transcriptases, seemed to be able to further extend the primer with
      another anhydrohexitol building block. Subsequently, several HIV-1 mutants
      (4xAZT, 4xAZT/L100I, L74V, M184V and K65A) were likewise analysed, resulting in
      selection of K65A and, in particular, M184V as the most succesful mutant HIV-1
      reverse transcriptases capable of elongating a DNA primer with several 1,5
      anhydrohexitol adenines in an efficient way. Results of kinetic experiments in
      the presence of this enzyme revealed that incorporation of one anhydrohexitol
      nucleotide of adenine or thymine gave an increased (for 1,5-anhydrohexitol-ATP)
      and a slightly decreased (for 1,5-anhydrohexitol-TTP) K(m) value in comparison to
      that of their natural counterparts. However, no more than four analogues could be
      inserted under the experimental conditions required for selective incorporation.
      Investigation of incorporation of the altritol anhydrohexitol nucleotide of
      adenine in the presence of M184V and Vent (exo(-)) DNA polymerase proved that an
      adjacent hydroxyl group on C3 of 1,5-anhydrohexitol-ATP has a detrimental effect
      on the substrate activity of the six-ring analogue. These results could be
      rationalised based on the X-ray structure of HIV-1 reverse transcriptase.

PMID- 11470873
TI  - Differences in telomere length between homologous chromosomes in humans.
AB  - Telomeres are important structures for DNA replication and chromosome stability
      during cell growth. Telomere length has been correlated with the division
      potential of human cells and has been found to decrease with age in healthy
      individuals. Nevertheless, telomere lengths within the same cell are
      heterogeneous and certain chromosome arms typically have either short or long
      telomeres. Both the origin and the physiological consequences of this
      heterogeneity in telomere length remain unknown. In this study we used
      quantitative telomeric FISH combined with a method to identify the parental
      origin of chromosomes to show that significant differences in relative telomere
      intensities are frequently observed between chromosomal homologs in short-term
      stimulated cultures of peripheral blood lymphocytes. These differences appear to
      be stable for at least 4 months in vivo, but disappear after prolonged
      proliferation in vitro. The telomere length differences are also stable during in
      vitro growth of telomerase-negative fibroblast cells but can be abolished by
      exogenous telomerase expression in these cells. These findings suggest the
      existence of a mechanism maintaining differences in telomere length between
      chromosome homologs that is independent of telomere length itself.

PMID- 11470874
TI  - Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3
      results in an impaired interaction with topoisomerase IIIalpha.
AB  - In higher eukaryotes, the integration of signals triggered in response to certain
      types of stress can result in programmed cell death. Central to these events is
      the sequential activation of a cascade of proteinases known as caspases. The
      final activated effector caspases of this cascade digest a number of cellular
      proteins, in some cases increasing their enzymatic activity, in others destroying
      their function. Of the proteins shown to be targets for caspase-mediated
      proteolysis, a surprisingly large proportion are proteins involved in the
      signalling or repair of DNA damage. Here we investigate whether BLM, the product
      of the gene mutated in Bloom's syndrome, a human autosomal disease characterised
      by cancer predisposition and sunlight sensitivity, is cleaved during apoptosis.
      BLM interacts with topoisomerase IIIalpha and has been proposed to play an
      important role in maintaining genomic integrity through its roles in DNA repair
      and replication. We show that BLM is cleaved during apoptosis by caspase-3 and
      reveal that the main cleavage site is located at the junction between the N
      terminal and central helicase domains of BLM. Proteolytic cleavage by caspase-3
      produces a 120 kDa fragment, which contains the intact helicase domain and three
      smaller fragments, the relative amounts of which depend on time of incubation
      with caspase-3. The 120 kDa fragment retains the helicase activity of the intact
      BLM protein. However, its interaction with topoisomerase IIIalpha is severely
      impaired. Since the BLM-topoisomerase interaction is believed to be necessary for
      many of the replication and recombination functions of BLM, we suggest that
      caspase-3 cleavage of BLM could alter the localisation and/or function of BLM and
      that these changes may be important in the process of apoptosis.

PMID- 11470875
TI  - Dynamics of association of origins of DNA replication with the nuclear matrix
      during the cell cycle.
AB  - DNA of replication foci attached to the nuclear matrix was isolated from Chinese
      hamster ovary cells and human HeLa cells synchronized at different stages of the
      G(1) and S phases of the cell cycle. The abundance of sequences from
      dihydrofolate reductase ori-beta and the beta-globin replicator was determined in
      matrix-attached DNA. The results show that matrix-attached DNA isolated from
      cells in late G(1) phase was enriched in origin sequences in comparison with
      matrix-attached DNA from early G(1) phase cells. The concentration of the early
      firing ori-beta in DNA attached to the matrix decreased in early S phase, while
      the late firing beta-globin origin remained attached until late S phase. We
      conclude that replication origins associate with the nuclear matrix in late G(1)
      phase and dissociate after initiation of DNA replication in S phase.

PMID- 11470876
TI  - Role of DNA minor groove interactions in substrate recognition by the M.SinI and
      M.EcoRII DNA (cytosine-5) methyltransferases.
AB  - The SinI and EcoRII DNA methyltransferases recognize sequences (GG(A)/(T)CC and
      CC(A)/(T)GG, respectively), which are characterized by an (A)/(T) ambiguity.
      Recognition of the A.T and T.A base pair was studied by in vitro
      methyltransferase assays using oligonucleotide substrates containing a
      hypoxanthine.C base pair in the central position of the recognition sequence.
      Both enzymes methylated the substituted oligonucleotide with an efficiency that
      was comparable to methylation of the canonical substrate. These observations
      indicate that M.SinI and M.EcoRII discriminate between their canonical
      recognition site and the site containing a G.C or a C.G base pair in the center
      of the recognition sequence (GG(G)/(C)CC and CC(G)/(C)GG, respectively) by
      interaction(s) in the DNA minor groove. M.SinI mutants displaying a decreased
      capacity to discriminate between the GG(A)/(T)CC and GG(G)/(C)CC sequences were
      isolated by random mutagenesis and selection for the relaxed specificity
      phenotype. These mutations led to amino acid substitutions outside the variable
      region, previously thought to be the sole determinant of sequence specificity.
      These observations indicate that (A)/(T) versus (G)/(C) discrimination is
      mediated by interactions between the large domain of the methyltransferase and
      the minor groove surface of the DNA.

PMID- 11470877
TI  - A human topoisomerase I cleavage complex is recognized by an additional human
      topisomerase I molecule in vitro.
AB  - Several recent studies have shown that human topoisomerase I (htopoI) can
      recognize various DNA lesions and thereby form a covalent topoisomerase I-DNA
      complex, which is known to be detrimental to cells. We have investigated whether
      htopoI recognizes another htopoI that is covalently trapped on a DNA substrate.
      For this purpose we created an artificial DNA substrate containing a specific
      topoisomerase I binding sequence, where the enzyme was trapped in the covalently
      bound form. We demonstrate that, in vitro, free htopoI stimulates the formation
      of an additional cleavage complex immediately upstream of the covalently bound
      topoisomerase I. The predominant distance between the two cleavage sites is 13
      nt. In addition we find that these two enzymes may form direct protein-protein
      contacts and we propose that these may be mediated through the formation of a
      dimer by domain swapping involving the C-terminal and the core domains. Finally,
      we discuss the possibility that the double cleavage reaction may be the initial
      step for the removal of the recognized cleavage complex.

PMID- 11470878
TI  - In vitro selection of exonic splicing enhancer sequences: identification of novel
      CD44 enhancers.
AB  - We have developed an in vitro selection procedure that allows the identification
      and isolation of functional splicing enhancer sequences from any cDNA. It is
      based on the enhancement of general splicing activity of a pre-mRNA reporter
      derived from the Drosophila dsx gene. Short DNase I fragments are cloned into a
      cassette in the second exon of the reporter construct, replacing the natural dsx
      enhancer. After splicing and reverse transcription-PCR, fragments are recovered
      from the mRNA product. Applying this selection to the CD44 gene, which undergoes
      extensive alternative splicing processes, we have identified several novel exonic
      enhancers. Two of them, which reside in CD44 variable exon 6, were further
      characterized by mutational analysis and confirmed to function within their
      natural CD44 context.

PMID- 11470879
TI  - Ribonucleotide reductase genes of Bacillus prophages: a refuge to introns and
      intein coding sequences.
AB  - The ribonucleotide reductase gene tandem bnrdE/bnrdF in SPbeta-related prophages
      of different Bacillus spp. isolates presents different configurations of
      intervening sequences, comprising one to three of six non-homologous splicing
      elements. Insertion sites of group I introns and intein DNA are clustered in
      three relatively short segments encoding functionally important domains of the
      ribonucleotide reductase. Comparison of the bnrdE homologs reveals mutual
      exclusion of a group I intron and an intein coding sequence flanking the codon
      that specifies a conserved cysteine. In vivo splicing was demonstrated for all
      introns. However, for two of them a part of the mRNA precursor molecules remains
      unspliced. Intergenic bnrdE-bnrdF regions are unexpectedly long, comprising
      between 238 and 541 nt. The longest encodes a putative polypeptide related to HNH
      homing endonucleases.

PMID- 11470880
TI  - Re-examination of the intrinsic, dynamic and hydration properties of
      phosphoramidate DNA.
AB  - Intrinsic energetic and solvation factors contributing to the unusual structural
      and biochemical properties of N3'-phosphoramidate DNA analogs have been re
      examined using a combination of quantum mechanical and molecular dynamics
      methods. Evaluation of the impact of the N3'-H substitution was performed via
      comparison of N3'-phosphoramidate DNA starting from both A- and B-form
      structures, B-form DNA and A-form RNA. The N3'-H group is shown to be flexible,
      undergoing reversible inversion transitions associated with motion of the
      hydrogen atom attached to the N3' atom. The inversion process is correlated with
      both sugar pucker characteristics as well as other local backbone torsional
      dynamics, yielding increased dihedral flexibility over DNA. Solvation of N3'
      phosphoramidate DNA is shown to be similar to RNA, consistent with thermodynamic
      data on the two species. A previously unobserved intrinsic conformational
      perturbation caused by the N5'-phosphoramidate substitution is identified and
      suggested to be linked to the differences in the properties of N3'- and N5'
      phosphoramidate oligonucleotide analogs.

PMID- 11470881
TI  - Effect of large targeted deletions on the mitotic stability of an extra
      chromosome mediating drug resistance in Leishmania.
AB  - A mitotically stable linear extra chromosome obtained in a Leishmania donovani
      strain rendered mycophenolic acid-resistant has been physically mapped. This 290
      kb chromosome has an inverted duplicated structure around a central inversion
      region, and is derived from a conservative amplification event of a approximately
      140-kb subtelomeric end of chromosome 19. Large-sized targeted deletions of the
      central region were performed through homologous recombination using three
      specific transfection vectors. The size of the extra chromosome was thus
      successfully reduced from 290 to 260, 200 and 120 kb respectively. The mitotic
      stability of these chromosomes was then analysed in drug-free cultures over >140
      days. Results differed according to the deletion created. By contrast with the
      smallest deletion the two largest deletions altered mitotic stability, leading to
      progressive loss of the size-reduced chromosomes with similar kinetics in both
      mutants. The 30-kb region common to both deletions may therefore be considered as
      involved in mitotic stability. A 44-kb contig covering this region could be
      assembled and sequenced. The analysis of this sequence did not reveal any
      sequence elements typical of centromeric DNA. By contrast, its enrichment in
      homopolymer tracts suggests that this region might contain an origin of
      replication.

PMID- 11470882
TI  - DNA looping in the RNA polymerase I enhancesome is the result of non-cooperative
      in-phase bending by two UBF molecules.
AB  - The so-called upstream binding factor (UBF) is required for the initial step in
      formation of an RNA polymerase I initiation complex. This function of UBF
      correlates with its ability to induce the ribosomal enhancesome, a structure
      which resembles in its mass and DNA content the nucleosome of chromatin. DNA
      looping in the enhancesome is probably the result of six in-phase bends induced
      by the HMG boxes of a UBF dimer. Here we show that insertion/deletion mutations
      in the basic peptide linker lying between the N-terminal dimerisation domain and
      the first HMG box of Xenopus UBF prevent the DNA looping characteristic of the
      enhancesome. Using these mutants we demonstrate that (i) the enhancesome
      structure does not depend on tethering of the entering and exiting DNA duplexes,
      (ii) UBF monomers induce hemi-enhancesomes, bending the DNA by 175 +/- 24 degrees
      and (iii) two hemi-enhancesomes are precisely phased by UBF dimerisation. We use
      this and previous data to refine the existing enhancesome model and show that HMG
      boxes 1 and 2 of UBF lie head-to-head along the DNA.

PMID- 11470883
TI  - Secondary structure prediction and structure-specific sequence analysis of single
      stranded DNA.
AB  - DNA sequence analysis by oligonucleotide binding is often affected by
      interference with the secondary structure of the target DNA. Here we describe an
      approach that improves DNA secondary structure prediction by combining enzymatic
      probing of DNA by structure-specific 5'-nucleases with an energy minimization
      algorithm that utilizes the 5'-nuclease cleavage sites as constraints. The method
      can identify structural differences between two DNA molecules caused by minor
      sequence variations such as a single nucleotide mutation. It also demonstrates
      the existence of long-range interactions between DNA regions separated by >300 nt
      and the formation of multiple alternative structures by a 244 nt DNA molecule.
      The differences in the secondary structure of DNA molecules revealed by 5'
      nuclease probing were used to design structure-specific probes for mutation
      discrimination that target the regions of structural, rather than sequence,
      differences. We also demonstrate the performance of structure-specific 'bridge'
      probes complementary to non-contiguous regions of the target molecule. The
      structure-specific probes do not require the high stringency binding conditions
      necessary for methods based on mismatch formation and permit mutation detection
      at temperatures from 4 to 37 degrees C. Structure-specific sequence analysis is
      applied for mutation detection in the Mycobacterium tuberculosis katG gene and
      for genotyping of the hepatitis C virus.

PMID- 11470884
TI  - Molecular evolution of the homeodomain family of transcription factors.
AB  - The homeodomain family of transcription factors plays a fundamental role in a
      diverse set of functions that include body plan specification, pattern formation
      and cell fate determination during metazoan development. Members of this family
      are characterized by a helix-turn-helix DNA-binding motif known as the
      homeodomain. Homeodomain proteins regulate various cellular processes by
      specifically binding to the transcriptional control region of a target gene.
      These proteins have been conserved across a diverse range of species, from yeast
      to human. A number of inherited human disorders are caused by mutations in
      homeodomain-containing proteins. In this study, we present an evolutionary
      classification of 129 human homeodomain proteins. Phylogenetic analysis of these
      proteins, whose sequences were aligned based on the three-dimensional structure
      of the homeodomain, was performed using a distance matrix approach. The
      homeodomain proteins segregate into six distinct classes, and this classification
      is consistent with the known functional and structural characteristics of these
      proteins. An ancestral sequence signature that accurately describes the unique
      sequence characteristics of each of these classes has been derived. The
      phylogenetic analysis, coupled with the chromosomal localization of these genes,
      provides powerful clues as to how each of these classes arose from the ancestral
      homeodomain.

PMID- 11470885
TI  - The weak interdomain coupling observed in the 70 kDa subunit of human replication
      protein A is unaffected by ssDNA binding.
AB  - Replication protein A (RPA) is a heterotrimeric, multi-functional protein that
      binds single-stranded DNA (ssDNA) and is essential for eukaryotic DNA metabolism.
      Using heteronuclear NMR methods we have investigated the domain interactions and
      ssDNA binding of a fragment from the 70 kDa subunit of human RPA (hRPA70). This
      fragment contains an N-terminal domain (NTD), which is important for hRPA70
      protein interactions, connected to a ssDNA-binding domain (SSB1) by a flexible
      linker (hRPA70(1-326)). Correlation analysis of the amide (1)H and (15)N chemical
      shifts was used to compare the structure of the NTD and SSB1 in hRPA70(1-326)
      with two smaller fragments that corresponded to the individual domains. High
      correlation coefficients verified that the NTD and SSB1 maintained their
      structures in hRPA70(1-326), indicating weak interdomain coupling. Weak
      interdomain coupling was also suggested by a comparison of the transverse
      relaxation rates for hRPA70(1-326) and one of the smaller hRPA70 fragments
      containing the NTD and the flexible linker (hRPA70(1-168)). We also examined the
      structure of hRPA70(1-326) after addition of three different ssDNA substrates.
      Each of these substrates induced specific amide (1)H and/or (15)N chemical shift
      changes in both the NTD and SSB1. The NTD and SSB1 have similar topologies,
      leading to the possibility that ssDNA binding induced the chemical shift changes
      observed for the NTD. To test this hypothesis we monitored the amide (1)H and
      (15)N chemical shift changes of hRPA70(1-168) after addition of ssDNA. The same
      amide (1)H and (15)N chemical shift changes were observed for the NTD in hRPA70(1
      168) and hRPA70(1-326). The NTD residues with the largest amide (1)H and/or (15)N
      chemical shift changes were localized to a basic cleft that is important for
      hRPA70-protein interactions. Based on this relationship, and other available
      data, we propose a model where binding between the NTD and ssDNA interferes with
      hRPA70-protein interactions.

PMID- 11470886
TI  - The role of DNA polymerase activity in human non-homologous end joining.
AB  - In mammalian cells, DNA double-strand breaks are repaired mainly by non
      homologous end joining, which modifies and ligates two DNA ends without requiring
      extensive base pairing interactions for alignment. We investigated the role of
      DNA polymerases in DNA-PK-dependent end joining of restriction-digested plasmids
      in vitro and in vivo. Rejoining of DNA blunt ends as well as those with partially
      complementary 5' or 3' overhangs was stimulated by 20-53% in HeLa cell-free
      extracts when dNTPs were included, indicating that part of the end joining is
      dependent on DNA synthesis. This DNA synthesis-dependent end joining was
      sensitive to aphidicolin, an inhibitor of alpha-like DNA polymerases.
      Furthermore, antibodies that neutralize the activity of DNA polymerase alpha were
      found to strongly inhibit end joining in vitro, whereas neutralizing antibodies
      directed against DNA polymerases beta and epsilon did not. DNA sequence analysis
      of end joining products revealed two prominent modes of repair, one of which
      appeared to be dependent on DNA synthesis. Identical products of end joining were
      recovered from HeLa cells after transfection with one of the model substrates,
      suggesting that the same end joining mechanisms also operate in vivo.
      Fractionation of cell extracts to separate PCNA as well as depletion of cell
      extracts for PCNA resulted in a moderate but significant reduction in end joining
      activity, suggesting a potential role in a minor repair pathway.

PMID- 11470887
TI  - A new approach for filtering noise from high-density oligonucleotide microarray
      datasets.
AB  - Although DNA microarrays are powerful tools for profiling gene expression, the
      dynamic range and the sheer number of signals produced require efficient
      procedures for distinguishing false positive results (noise) from changes in
      expression that are 'real' (independently reproducible). We have developed an
      approach to filter noise from datasets generated when high density
      oligonucleotide-based microarrays are used to compare two distinct RNA
      populations. First, we performed comparisons between chips hybridized with cRNAs
      prepared from an identical starting RNA population; an 'Increase' or 'Decrease'
      call in such a comparison was defined as a false positive. Plotting the average
      distribution of these false positive signal intensities across 18 such
      comparisons of nine independent RNA preparations allowed us to develop a series
      of noise-filtering look-up tables (LUTs). Using a database of 70 separate chip-to
      chip comparisons between distinct RNA preparations prepared by different workers
      at different sites and at different times, we show that the LUTs can be used to
      predict the likelihood that a given transcript called Increased or Decreased in
      one comparison will again be called Increased or Decreased in a replicate
      comparison. Evidence is presented that this LUT-based scoring system provides
      greater predictive value for reproducible microarray results than imposition of
      arbitrary fold-change thresholds and accurately predicts which microarray
      identified changes will be validated by independent assays such as quantitative
      real-time PCR.

PMID- 11470888
TI  - Single step generation of protein arrays from DNA by cell-free expression and in
      situ immobilisation (PISA method).
AB  - We describe a format for production of protein arrays termed 'protein in situ
      array' (PISA). A PISA is rapidly generated in one step directly from PCR
      generated DNA fragments by cell-free protein expression and in situ
      immobilisation at a surface. The template for expression is DNA encoding
      individual proteins or domains, which is produced by PCR using primers designed
      from information in DNA databases. Coupled transcription and translation is
      carried out on a surface to which the tagged protein adheres as soon as it is
      synthesised. Because proteins generated by cell-free synthesis are usually
      soluble and functional, this method can overcome problems of insolubility or
      degradation associated with bacterial expression of recombinant proteins.
      Moreover, the use of PCR-generated DNA enables rapid production of proteins or
      domains based on genome information alone and will be particularly useful where
      cloned material is not available. Here we show that human single-chain antibody
      fragments (three domain, V(H)/K form) and an enzyme (luciferase) can be
      functionally arrayed by the PISA method.

PMID- 11470889
TI  - The determination of complete human mitochondrial DNA sequences in single cells:
      implications for the study of somatic mitochondrial DNA point mutations.
AB  - Studies of single cells have previously shown intracellular clonal expansion of
      mitochondrial DNA (mtDNA) mutations to levels that can cause a focal cytochrome c
      oxidase (COX) defect. Whilst techniques are available to study mtDNA
      rearrangements at the level of the single cell, recent interest has focused on
      the possible role of somatic mtDNA point mutations in ageing, neurodegenerative
      disease and cancer. We have therefore developed a method that permits the
      reliable determination of the entire mtDNA sequence from single cells without
      amplifying contaminating, nuclear-embedded pseudogenes. Sequencing and PCR-RFLP
      analyses of individual COX-negative muscle fibres from a patient with a
      previously described heteroplasmic COX II (T7587C) mutation indicate that mutant
      loads as low as 30% can be reliably detected by sequencing. This technique will
      be particularly useful in identifying the mtDNA mutational spectra in age-related
      COX-negative cells and will increase our understanding of the pathogenetic
      mechanisms by which they occur.

PMID- 11470890
TI  - Quantitative quality control in microarray image processing and data acquisition.
AB  - A new integrated image analysis package with quantitative quality control schemes
      is described for cDNA microarray technology. The package employs an iterative
      algorithm that utilizes both intensity characteristics and spatial information of
      the spots on a microarray image for signal-background segmentation and defines
      five quality scores for each spot to record irregularities in spot intensity,
      size and background noise levels. A composite score q(com) is defined based on
      these individual scores to give an overall assessment of spot quality. Using
      q(com) we demonstrate that the inherent variability in intensity ratio
      measurements is closely correlated with spot quality, namely spots with higher
      quality give less variable measurements and vice versa. In addition, gauging data
      by q(com) can improve data reliability dramatically and efficiently. We further
      show that the variability in ratio measurements drops exponentially with
      increasing q(com) and, for the majority of spots at the high quality end, this
      improvement is mainly due to an improvement in correlation between the two dyes.
      Based on these studies, we discuss the potential of quantitative quality control
      for microarray data and the possibility of filtering and normalizing microarray
      data using a quality metrics-dependent scheme.

PMID- 11470891
TI  - Folding and signaling share the same pathway in a photoreceptor.
AB  - The photoreceptor photoactive yellow protein (PYP) was used as a model system to
      study receptor activation and protein folding. Refolding was studied by stopped
      flow absorbance spectroscopy for PYP with either a trans or a cis chromophore.
      Chromophore trans to cis isomerization, the mechanism of light detection by PYP,
      greatly affects the protein folding process. When the cis chromophore is present,
      refolding from the unfolded state proceeds through the putative signaling state
      of PYP as an on-pathway intermediate. In addition, moderate denaturant
      concentrations result in the specific unfolding of the signaling state of PYP.
      Thus, the signaling state is common to the pathways of folding and signaling.
      This result provides an avenue for the study of protein folding. We demonstrate
      how this approach can be used to establish whether a folding intermediate is on
      pathway or off-pathway. The results also reveal transient partial unfolding as a
      molecular mechanism for signaling.

PMID- 11470892
TI  - Energetic asymmetry among hydrogen bonds in MHC class II*peptide complexes.
AB  - Comparison of crystallized MHC class II*peptide complexes has revealed that, in
      addition to pocket interactions involving the peptide side chains, peptide
      binding to MHC class II molecules is characterized by a series of hydrogen bonds
      between genetically conserved amino acid residues in the class II molecule and
      the main chain of the peptide. Many class II*peptide structures have two sets of
      symmetrical hydrogen bonds at the opposite ends of the class II antigen-binding
      groove (beta-His-81, beta-Asn-82 vs. alpha-His-68, alpha-Asn-69). In this study,
      we alter these peripheral hydrogen bonds and measure the apparent contribution of
      each to the kinetic stability of peptide* II complexes. Single conservative amino
      substitutions were made in the I-A(d) protein to eliminate participation as a
      hydrogen bonding residue, and the kinetic stability of a diverse set of peptides
      bound to the substituted I-A(d) proteins was measured. Although each hydrogen
      bond does contribute to peptide binding, our results point to the striking
      conclusion that those hydrogen bonds localized to the amino terminus of the
      peptide contribute profoundly and disproportionately to the stability of peptide
      interactions with I-A(d). We suggest that the peripheral hydrogen bonds at the
      amino terminus of the bound peptide that are conserved in all class II*peptide
      crystal structures solved thus far form a cooperative network that critically
      regulates peptide dissociation from the class II molecule.

PMID- 11470893
TI  - Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells
      abrogated by exposure to a prion protein antibody.
AB  - Exposure of susceptible neuroblastoma N2a cells to mouse scrapie prions leads to
      infection, as evidenced by the continued presence of the scrapie form of the
      prion protein (PrP(Sc)) and infectivity after 300 or more cell doublings. We find
      that exposure to phosphatidylinositol-specific phospholipase C (PIPLC) or to the
      monoclonal anti-prion protein (PrP) antibody 6H4 not only prevents infection of
      susceptible N2a cells but also cures chronically scrapie-infected cultures, as
      judged by the long-term abrogation of PrP(Sc) accumulation after cessation of
      treatment. A nonpassaged, stationary infected culture rapidly loses PrP(Sc) when
      exposed to the antibody or PIPLC, indicating that the PrP(Sc) level is determined
      by steady state equilibrium between formation and degradation, and that depletion
      of the cellular form of PrP can interrupt the propagation of PrP(Sc). These
      findings encourage the belief that passive immunization may provide a therapeutic
      approach to prion disease.

PMID- 11470894
TI  - Effects of DNA sequence and structure on binding of RecA to single-stranded DNA.
AB  - Fluorescence anisotropy is used to follow the binding of RecA to short single
      stranded DNA (ssDNA) sequences (39 bases) at low DNA and RecA concentration where
      the initial phase of polymerization occurs. We observe that RecA condensation is
      extremely sensitive to minute changes in DNA sequences. RecA binds strongly to
      sequences that are rich in pyrimidines and that lack significant secondary
      structure and base stacking. We find a correlation between the DNA folding free
      energy and the onset concentration for RecA binding. These results suggest that
      the folding of ssDNA and base stacking represent a barrier for RecA binding. The
      link between secondary structure and binding affinity is further analyzed with
      two examples: discrimination between two naturally occurring polymorphisms
      differing by one base and RecA binding on a molecular beacon. A self-assembly
      model is introduced to explain these observations. We propose that RecA may be
      used to sense ssDNA sequence and structure.

PMID- 11470896
TI  - Evolutionary self-organization of cell-free genetic coding.
AB  - Genetic encoding provides a generic construction scheme for biomolecular
      functions. This paper addresses the key problem of coevolution and exploitation
      of the multiple components necessary to implement a replicable genetic encoding
      scheme. Extending earlier results on multicomponent replication, the necessity of
      spatial structure for the evolutionary stabilization of the genetic coding system
      is established. An individual-based stochastic model of interacting molecules in
      three-dimensional space is presented that allows the evolution of genetic coding
      to be analyzed explicitly. A massively parallel configurable computer (NGEN) is
      used to implement the model, on the time scale of millions of generations,
      directly in electronic hardware. The spatial correlations between components of
      the genetic coding system are analyzed and found to be essential for evolutionary
      stability.

PMID- 11470895
TI  - Patterns of DNA sequence polymorphism along chromosome 1 of maize (Zea mays ssp.
      mays L.).
AB  - We measured sequence diversity in 21 loci distributed along chromosome 1 of maize
      (Zea mays ssp. mays L.). For each locus, we sequenced a common sample of 25
      individuals representing 16 exotic landraces and nine U.S. inbred lines. The data
      indicated that maize has an average of one single nucleotide polymorphism (SNP)
      every 104 bp between two randomly sampled sequences, a level of diversity higher
      than that of either humans or Drosophila melanogaster. A comparison of genetic
      diversity between the landrace and inbred samples showed that inbreds retained
      77% of the level of diversity of landraces, on average. In addition, Tajima's D
      values suggest that the frequency distribution of polymorphisms in inbreds was
      skewed toward fewer rare variants. Tests for selection were applied to all loci,
      and deviations from neutrality were detected in three loci. Sequence diversity
      was heterogeneous among loci, but there was no pattern of diversity along the
      genetic map of chromosome 1. Nonetheless, diversity was correlated (r = 0.65)
      with sequence-based estimates of the recombination rate. Recombination in our
      sample was sufficient to break down linkage disequilibrium among SNPs. Intragenic
      linkage disequilibrium declines within 100-200 bp on average, suggesting that
      genome-wide surveys for association analyses require SNPs every 100-200 bp.

PMID- 11470897
TI  - Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the
      peptidyltransferase active site of the 50S ribosomal subunit.
AB  - On the basis of the recent atomic-resolution x-ray structure of the 50S ribosomal
      subunit, residues A2451 and G2447 of 23S rRNA were proposed to participate
      directly in ribosome-catalyzed peptide bond formation. We have examined the
      peptidyltransferase and protein synthesis activities of ribosomes carrying
      mutations at these nucleotides. In Escherichia coli, pure mutant ribosome
      populations carrying either the G2447A or G2447C mutations maintained cell
      viability. In vitro, the G2447A ribosomes supported protein synthesis at a rate
      comparable to that of wild-type ribosomes. In single-turnover peptidyltransferase
      assays, G2447A ribosomes were shown to have essentially unimpaired
      peptidyltransferase activity at saturating substrate concentrations. All three
      base changes at the universally conserved A2451 conferred a dominant lethal
      phenotype when expressed in E. coli. Nonetheless, significant amounts of 2451
      mutant ribosomes accumulated in polysomes, and all three 2451 mutations
      stimulated frameshifting and readthrough of stop codons in vivo. Furthermore,
      ribosomes carrying the A2451U transversion synthesized full-length beta-lactamase
      chains in vitro. Pure mutant ribosome populations with changes at A2451 were
      generated by reconstituting Bacillus stearothermophilus 50S subunits from in
      vitro transcribed 23S rRNA. In single-turnover peptidyltransferase assays, the
      rate of peptide bond formation was diminished 3- to 14-fold by these mutations.
      Peptidyltransferase activity and in vitro beta-lactamase synthesis by ribosomes
      with mutations at A2451 or G2447 were highly resistant to chloramphenicol. The
      significant levels of peptidyltransferase activity of ribosomes with mutations at
      A2451 and G2447 need to be reconciled with the roles proposed for these residues
      in catalysis.

PMID- 11470898
TI  - Circadian rhythms of female mating activity governed by clock genes in
      Drosophila.
AB  - The physiological and behavioral activities of many animals are restricted to
      specific times of the day. The daily fluctuation in the mating activity of some
      insects is controlled by an endogenous clock, but the genetic mechanism that
      controls it remains unknown. Here we demonstrate that wild-type Drosophila
      melanogaster display a robust circadian rhythm in the mating activity, and that
      these rhythms are abolished in period- or timeless-null mutant flies (per(01) and
      tim(01)). Circadian rhythms were lost when rhythm mutant females were paired with
      wild-type males, demonstrating that female mating activity is governed by clock
      genes. Furthermore, we detected an antiphasic relationship in the circadian
      rhythms of mating activity between D. melanogaster and its sibling species
      Drosophila simulans. Female- and species-specific circadian rhythms in the mating
      activity of Drosophila seem to cause reproductive isolation.

PMID- 11470899
TI  - Neuroinvasion by a Creutzfeldt-Jakob disease agent in the absence of B cells and
      follicular dendritic cells.
AB  - With the potential spread of bovine spongiform encephalopathy to people as a
      variant Creutzfeldt-Jakob disease (CJD), it becomes critical to identify cells in
      the periphery that carry infection. Initial work with scrapie agents suggested
      that B cells were central vectors for neuroinvasion. Subsequent studies indicated
      that B cells played an indirect role by promoting the development of follicular
      dendritic cells (FDCs) that accumulate abnormal prion protein (PrP). The
      mechanism for the role of FDCs, however, has not been clear. To further dissect
      potential B cell functions that contribute to neuroinvasion, we inoculated a CJD
      agent into mutant mice that (i) lacked B cells, (ii) had B cells unable to
      secrete Ig, or (iii) could secrete only IgM. Remarkably, all these mice developed
      disease with practically indistinguishable incubation times. The demonstration
      that neither immune complexes nor B cells were required for neuroinvasion from
      the periphery mandates a reanalysis of the accepted view of the essential role of
      B cells and FDC in these infections. Moreover, immune complexes were not required
      for the accumulation of pathologic PrP on the surface of FDCs, suggesting that
      PrP can bind to FDCs autonomously or by means of another factor. Wild-type mice
      had incubation times approximately 50 days less than all mutant mice at the same
      peripheral doses, indicating that an intact immune system may increase agent
      uptake and delivery, but this condition is not essential. Specifically, the
      evidence to date suggests that IgG may enhance pivotal agent interactions with
      migratory myeloid cells.

PMID- 11470900
TI  - Function of the bacterial TATAAT -10 element as single-stranded DNA during RNA
      polymerase isomerization.
AB  - The bacterial TATAAT -10 region sequence was the first promoter element to be
      identified, but how it functions is still not clear. Because the duplex element
      is melted during initiation, the effects of substitutions were studied in both
      single-and double-strand contexts. Band-shift results were particularly
      unexpected in the context of melted DNA. The effect of the lac UV5-melted -10
      region on polymerase binding was found to include a large sequence nonspecific
      contribution. Instead the dominant role of single-stranded -10 region nucleotides
      was in directing the isomerization of the RNA polymerase to its heparin resistant
      form. This role becomes minimal when the melting is extended beyond the -10
      region to encompass the transcription start site, as in the final open complex.
      The duplex binding results are in agreement with previous reports that showed
      positions -12T and -11A are of primary importance for promoter recognition. Thus
      the consensus -10 region sequences function in two ways, both before full
      promoter melting. They stabilize initial polymerase binding via duplex
      interactions and subsequently as single-stranded DNA they promote enzyme
      isomerization to the functional form.

PMID- 11470901
TI  - Expression cloning of two genes that together mediate organic solute and steroid
      transport in the liver of a marine vertebrate.
AB  - Uptake of organic solutes and xenobiotics by mammalian cells is mediated by ATP
      independent transporters, and four families of transporters have now been
      identified. To search for novel organic solute transporters, a liver cDNA library
      from an evolutionarily primitive marine vertebrate, the little skate Raja
      erinacea, was screened for taurocholate transport activity by using Xenopus
      laevis oocytes. In contrast to the organic anion transporters identified to date,
      a transport activity was identified in this library that required the
      coexpression of two distinct gene products, termed organic solute transporter
      alpha and beta (Ostalpha, Ostbeta). Ostalpha cDNA encodes for a protein of 352 aa
      and seven putative transmembrane (TM) domains. Ostbeta contains 182 aa and has at
      least one and perhaps two TM domains. There is no significant sequence identity
      between Ostalpha and Ostbeta, and only low identity with sequences in the
      databases; however, Ostalpha bears a resemblance to some G protein-coupled
      receptors, and Ostbeta exhibits 22% amino acid identity with the C-terminal TM
      and intracellular domains of protocadherin-gamma, a cell surface glycoprotein.
      Xenopus oocytes injected with the cRNA for both Ostalpha and Ostbeta, but not
      each separately, were able to take up taurocholate, estrone sulfate, digoxin, and
      prostaglandin E(2), but not p-aminohippurate or S-dinitrophenyl glutathione.
      Transport was sodium-independent, saturable, and inhibited by organic anions and
      steroids, including the major skate bile salt, scymnol sulfate. These results
      identify an organic anion transporter composed of a putative seven-helix TM
      protein and an ancillary membrane polypeptide.

PMID- 11470902
TI  - Presenilin-dependent gamma-secretase activity modulates thymocyte development.
AB  - In neuronal cells, presenilin-dependent gamma-secretase activity cleaves amyloid
      precursor proteins to release Abeta peptides, and also catalyzes the release of
      the intracellular domain of the transmembrane receptor Notch. Accumulation of
      aberrant Abeta peptides appears to be causally related to Alzheimer's disease.
      Inhibition of Abeta peptide production is therefore a potential target for
      therapeutic intervention. Notch proteins play an important role in cell fate
      determination in many different organisms and at different stages of development,
      for example in mammalian T cell development. We therefore addressed whether
      structurally diverse gamma-secretase inhibitors impair Notch function by studying
      thymocyte development in murine fetal thymic organ cultures. Here we show that
      high concentrations of the most potent inhibitors blocked thymocyte development
      at the most immature stage. In contrast, lower concentrations or less potent
      inhibitors impaired differentiation at a later stage, most notably suppressing
      the development of CD8 single-positive T cells. These phenotypes are consistent
      with an impairment of Notch signaling by gamma-secretase inhibitors and define a
      strict Notch dose dependence of consecutive stages during thymocyte development.

PMID- 11470903
TI  - Reproductive aging and mating: the ticking of the biological clock in female
      cockroaches.
AB  - Females are expected to have different mating preferences because of the
      variation in costs and benefits of mate choice both between females and within
      individual females over a lifetime. Workers have begun to look for, and find, the
      expected variation among females in expressed mating preferences. However,
      variation within females caused by changes in intrinsic influences has not been
      examined in detail. Here we show that reproductive aging caused by delayed mating
      resulted in reduced choosiness by female Nauphoeta cinerea, a cockroach that has
      reproductive cycles and gives live birth. Male willingness to mate was unaffected
      by variation in female age. Females who were beyond the optimal mating age, 6
      days postadult molt, required considerably less courtship than their younger
      counterparts. Females who were older when they mated had fewer offspring per
      clutch and fewer clutches than females who mated young. Thus, reduced choosiness
      was correlated with a permanent reduction in fertility. There was no difference
      in overall senescence among females, and thus the reduction in clutch size did
      not result in the expected increased lifespan. We suggest that reproductive aging
      in N. cinerea, similar to aging in general, occurs because the maintenance of
      oocytes is costly, and selection is relaxed after the optimal mating period. Our
      results further suggest that selection for continued choosiness is also relaxed
      and supports direct selection on female choosiness and a cost to choosiness.

PMID- 11470904
TI  - A conserved RNA structure (thi box) is involved in regulation of thiamin
      biosynthetic gene expression in bacteria.
AB  - The thiCOGE genes of Rhizobium etli code for enzymes involved in thiamin
      biosynthesis. These genes are transcribed with a 211-base untranslated leader
      that contains the thi box, a 38-base sequence highly conserved in the 5' regions
      of thiamin biosynthetic and transport genes of Gram-positive and Gram-negative
      organisms. A deletion analysis of thiC-lacZ fusions revealed an unexpected
      relationship between the degree of repression shown by the deleted derivatives
      and the length of the thiC sequences present in the transcript. Three regions
      were found to be important for regulation: (i) the thi box sequence, which is
      absolutely necessary for high-level expression of thiC; (ii) the region
      immediately upstream to the translation start codon of thiC, which can be folded
      into a stem-loop structure that would mask the Shine-Dalgarno sequence; and (iii)
      the proximal part of the coding region of thiC, which was shown to contain a
      putative Rho-independent terminator. A comparative phylogenetic analysis revealed
      a possible folding of the thi box sequence into a hairpin structure composed of a
      hairpin loop, two helices, and an interior loop. Our results show that thiamin
      regulation of gene expression involves a complex posttranscriptional mechanism
      and that the thi box RNA structure is indispensable for thiCOGE expression.

PMID- 11470905
TI  - Structural rationale for the modulation of abscess formation by Staphylococcus
      aureus capsular polysaccharides.
AB  - Staphylococcus aureus is a medically important bacterial pathogen that is a
      common cause of superficial and deep-seated abscesses in humans. Most S. aureus
      isolates produce either a serotype 5 or 8 capsular polysaccharide (CP) that has
      been shown to enhance bacterial virulence. We investigated the role of S. aureus
      CPs in modulating abscess formation in an experimental animal model of
      intraabdominal infection. Structural studies of CP8 revealed that it has a
      zwitterionic charge motif conferred by the negatively charged carboxyl group of N
      acetylmannosaminuronic acid and free amino groups available on partially N
      acetylated fucosamine residues. We report that purified CP5 and CP8 facilitated
      intraabdominal abscess formation in animals when given i.p. with a sterile cecal
      contents adjuvant. Chemical modifications that neutralized the positively or
      negatively charged groups on CP8 abrogated its ability to provoke abscesses. Rats
      prophylactically treated with CP8 s.c. were protected against abscess formation
      induced by homologous or heterologous zwitterionic polysaccharides. Likewise,
      treatment with CP8 protected against challenge with viable S. aureus strains PS80
      (a capsule type 8 strain) or COL (a methicillin-resistant capsule type 5 strain).
      Purified CP8 was a potent activator of rat and human CD4(+) T cells in vitro.
      When transferred to naive rats, these activated T cells modulated the development
      of intraabdominal abscess formation. These results provide a structure/function
      rationale for abscess formation by S. aureus and expand the sphere of
      encapsulated organisms that interact directly with T cells to regulate this host
      response to bacterial infection.

PMID- 11470906
TI  - Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in
      mice lacking fatty acid amide hydrolase.
AB  - The medicinal properties of marijuana have been recognized for centuries, but
      clinical and societal acceptance of this drug of abuse as a potential therapeutic
      agent remains fiercely debated. An attractive alternative to marijuana-based
      therapeutics would be to target the molecular pathways that mediate the effects
      of this drug. To date, these neural signaling pathways have been shown to
      comprise a cannabinoid receptor (CB(1)) that binds the active constituent of
      marijuana, tetrahydrocannabinol (THC), and a postulated endogenous CB(1) ligand
      anandamide. Although anandamide binds and activates the CB(1) receptor in vitro,
      this compound induces only weak and transient cannabinoid behavioral effects in
      vivo, possibly a result of its rapid catabolism. Here we show that mice lacking
      the enzyme fatty acid amide hydrolase (FAAH(-/-)) are severely impaired in their
      ability to degrade anandamide and when treated with this compound, exhibit an
      array of intense CB(1)-dependent behavioral responses, including hypomotility,
      analgesia, catalepsy, and hypothermia. FAAH(-/-)-mice possess 15-fold augmented
      endogenous brain levels of anandamide and display reduced pain sensation that is
      reversed by the CB(1) antagonist SR141716A. Collectively, these results indicate
      that FAAH is a key regulator of anandamide signaling in vivo, setting an
      endogenous cannabinoid tone that modulates pain perception. FAAH may therefore
      represent an attractive pharmaceutical target for the treatment of pain and
      neuropsychiatric disorders.

PMID- 11470907
TI  - Colonization of America by Drosophila subobscura: heterotic effect of chromosomal
      arrangements revealed by the persistence of lethal genes.
AB  - About 20 years ago Drosophila subobscura, a native Palearctic species, colonized
      both North and South America. In Palearctic populations lethal genes are not
      associated in general with particular chromosomal arrangements. In colonizing
      populations they are not randomly distributed and usually are associated to a
      different degree with chromosomal arrangements caused by the founder event. The
      persistence of two lethal genes in the colonizing populations, one completely
      associated with the O(5) inversion and the other partially associated with the
      O(3+4+7) arrangement, has been analyzed. In all populations studied (five North
      American and six South American) the observed frequency of the lethal gene
      completely associated with the O(5) inversion is higher than expected, the
      difference being statistically significant in all South American and one North
      American populations. The observed frequency of the lethal gene partially
      associated with the O(3+4+7) arrangement is also significantly higher than
      expected. Taking into account that the O(5) inversion exhibits significant
      latitudinal clines both in North and South America, an overdominant model
      favoring the heterokaryotypes seems to be in operation. From this model, a
      polynomial expression has been developed that allows us to estimate the relative
      fitness and the coefficient of selection against all karyotypes not carrying the
      O(5) inversion. The relative fitness of the O(5) heterokaryotypes is higher in
      South American than in North American populations. Furthermore, the observed
      frequencies of the lethal genes studied are in general very close to those of the
      equilibrium. This case is an outstanding demonstration in nature of an heterotic
      effect of chromosomal segments associated with lethal genes on a large geographic
      scale.

PMID- 11470909
TI  - Bootstrapping cluster analysis: assessing the reliability of conclusions from
      microarray experiments.
AB  - We introduce a general technique for making statistical inference from clustering
      tools applied to gene expression microarray data. The approach utilizes an
      analysis of variance model to achieve normalization and estimate differential
      expression of genes across multiple conditions. Statistical inference is based on
      the application of a randomization technique, bootstrapping. Bootstrapping has
      previously been used to obtain confidence intervals for estimates of differential
      expression for individual genes. Here we apply bootstrapping to assess the
      stability of results from a cluster analysis. We illustrate the technique with a
      publicly available data set and draw conclusions about the reliability of
      clustering results in light of variation in the data. The bootstrapping procedure
      relies on experimental replication. We discuss the implications of replication
      and good design in microarray experiments.

PMID- 11470908
TI  - IL-7 differentially regulates cell cycle progression and HIV-1-based vector
      infection in neonatal and adult CD4+ T cells.
AB  - Differences in the immunological reactivity of umbilical cord (UC) and adult
      peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a
      cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB
      and UC lymphocytes. Neither naive nor memory APB CD4(+) cells proliferated in
      response to IL-7, whereas naive UC CD4(+) lymphocytes underwent multiple
      divisions. Nevertheless, both naive and memory IL-7-treated APB T cells
      progressed into the G(1b) phase of the cell cycle, albeit at higher levels in the
      latter subset. The IL-7-treated memory CD4(+) lymphocyte population was
      significantly more susceptible to infection with an HIV-1-derived vector than
      dividing CD4(+) UC lymphocytes. However, activation through the T cell receptor
      rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These
      data unveil differences between UC and APB CD4(+) T cells with regard to IL-7
      mediated cell cycle progression and HIV-1-based vector infectivity. This evidence
      indicates that IL-7 differentially regulates lymphoid homeostasis in adults and
      neonates.

PMID- 11470910
TI  - Firing rates of hippocampal neurons are preserved during subsequent sleep
      episodes and modified by novel awake experience.
AB  - What determines the firing rate of cortical neurons in the absence of external
      sensory input or motor behavior, such as during sleep? Here we report that, in a
      familiar environment, the discharge frequency of simultaneously recorded
      individual CA1 pyramidal neurons and the coactivation of cell pairs remain highly
      correlated across sleep-wake-sleep sequences. However, both measures were
      affected when new sets of neurons were activated in a novel environment.
      Nevertheless, the grand mean firing rate of the whole pyramidal cell population
      remained constant across behavioral states and testing conditions. The findings
      suggest that long-term firing patterns of single cells can be modified by
      experience. We hypothesize that increased firing rates of recently used neurons
      are associated with a concomitant decrease in the discharge activity of the
      remaining population, leaving the mean excitability of the hippocampal network
      unaltered.

PMID- 11470911
TI  - Paradoxical intrathymic positive selection in mice with only a covalently
      presented agonist peptide.
AB  - The Y-Ae mAb and the 1H3.1 alphabeta T cell antigen receptor (TCR) are both
      specific for the I-Ealpha52-68 peptide bound to the I-A(b) major
      histocompatibility complex (MHC) class II molecule. Antigen-presenting cells
      (APCs) from I-A(b+) mice with a natural or transgenic (Tg) I-Ealpha chain
      activate mature 1H3.1 T cells and cause the deletion of 1H3.1 TCR Tg thymocytes.
      However, 1H3.1 T cells were neither activated nor inactivated by confrontation
      with APCs from I-Ab-Ep mice in which I-A(b) molecules are occupied only by the
      covalently associated Ealpha52-68 peptide. Instead, immature 1H3.1 TCR Tg
      thymocytes were efficiently positively selected into the CD4 lineage in the I-Ab
      Ep thymus. This selection relied on specific recognition of the Ealpha52-68/I
      A(b) complex because it was blocked by Y-Ae. 1H3.1 TCR Tg T cells maturing in the
      I-Ab-Ep thymus efficiently populated the periphery, displayed a naive phenotype,
      and were specifically reactive to the Ealpha52-68 peptide or to I-A(b+)I
      Ealpha(+) APCs, indicating that 1H3.1 T cells were not antagonized in I-Ab-Ep
      mice. The data identify major histocompatibility complex class II molecules with
      only a covalently attached self-peptide as a ligand for in vivo positive
      selection of T cells specific for the same peptide.

PMID- 11470912
TI  - The subunit structure and catalytic mechanism of the Bacillus subtilis DNA repair
      enzyme spore photoproduct lyase.
AB  - The major DNA photoproduct of dormant, UV-irradiated Bacillus subtilis spores is
      the thymine dimer 5-thyminyl-5,6-dihydrothymine [spore photoproduct (SP)]. During
      spore germination, SP is reversed to two intact thymines in situ by the DNA
      repair enzyme SP lyase, an S-adenosylmethionine (S-AdoMet)-dependent iron-sulfur
      ([Fe-S]) protein encoded by the splB gene. In the present work, cross-linking,
      SDS/PAGE, and size exclusion chromatography revealed that SplB protein dimerized
      when incubated with iron and sulfide under anaerobic reducing conditions. SplB
      isolated under aerobic conditions generated an EPR spectrum consistent with that
      of a partially degraded [3Fe-4S] center, and reduction of SplB with dithionite
      shifted the spectrum to that of a [4Fe-4S] center. Addition of S-AdoMet to SplB
      converted some of the [4Fe-4S] centers to an EPR-silent form consistent with
      electron donation to S-AdoMet. HPLC and electrospray ionization MS analyses
      showed that SP lyase cleaved S-AdoMet to generate 5'-deoxyadenosine. The results
      indicate that (i) SP lyase is a homodimer of SplB; (ii) dimer formation is
      coordinated by a [4Fe-4S] center; and (iii) the reduced [4Fe-4S] center is
      capable of donating electrons to S-AdoMet to generate a 5'-adenosyl radical that
      is then used for the in situ reversal of SP. Thus, SP lyase belongs to the
      "radical SAM" superfamily of enzymes that use [Fe-S] centers and S-AdoMet to
      generate adenosyl radicals to effect catalysis. SP lyase is unique in being the
      first and only DNA repair enzyme known to function via this novel enzymatic
      mechanism.

PMID- 11470913
TI  - Strength and tempo of directional selection in the wild.
AB  - Directional selection is a major force driving adaptation and evolutionary
      change. However, the distribution, strength, and tempo of phenotypic selection
      acting on quantitative traits in natural populations remain unclear across
      different study systems. We reviewed the literature (1984-1997) that reported the
      strength of directional selection as indexed by standardized linear selection
      gradients (beta). We asked how strong are viability and sexual selection, and
      whether strength of selection is correlated with the time scale over which it was
      measured. Estimates of the magnitude of directional selection (absolute value of
      beta) were exponentially distributed, with few estimates greater than 0.50 and
      most estimates less than 0.15. Sexual selection (measured by mating success)
      appeared stronger than viability selection (measured by survival). Viability
      selection that was measured over short periods (days) was typically stronger than
      selection measured over longer periods (months and years), but the strength of
      sexual selection did not vary with duration of selection episodes; as a result,
      sexual selection was stronger than viability selection over longer time scales
      (months and years), but not over short time scales (days).

PMID- 11470914
TI  - Rac1 mediates STAT3 activation by autocrine IL-6.
AB  - The activity of the small GTPase, Rac1, plays a role in various cellular
      processes including cytoskeletal rearrangement, gene transcription, and malignant
      transformation. In this report constitutively active Rac1 (Rac V12) is shown to
      stimulate the activation of STAT3, a member of the family of signal transducers
      and activators of transcription (STATs). The activity of Rac1 leads to STAT3
      translocation to the nucleus coincident with STAT3-dependent gene expression. The
      expression of Vav (Delta1-187), a constitutively active guanine nucleotide
      exchange factor for the Rho GTPases, or activated forms of Ras or Rho family
      members, leads to STAT3-specific activation. The activation of STAT3 requires
      tyrosine phosphorylation at residue 705, but is not dependent on phosphorylation
      of Ser-727. Our studies indicate that Rac1 induces STAT3 activation through an
      indirect mechanism that involves the autocrine production and action of IL-6, a
      known mediator of STAT3 response. Rac V12 expression results in the induction of
      the IL-6 and IL-6 receptor genes and neutralizing antibodies directed against the
      IL-6 receptor block Rac1-induced STAT3 activation. Furthermore, inhibition of the
      nuclear factor-kappaB activation or disruption of IL-6-mediated signaling through
      the expression of IkappaBalpha S32AS36A and suppressor of cytokine signaling 3,
      respectively, blocks Rac1-induced STAT3 activation. These findings elucidate a
      mechanism dependent on the induction of an autocrine IL-6 activation loop through
      which Rac1 mediates STAT3 activation establishing a link between oncogenic GTPase
      activity and Janus kinase/STAT signaling.

PMID- 11470915
TI  - Insulin alters heterogeneous nuclear ribonucleoprotein K protein binding to DNA
      and RNA.
AB  - The interaction of the multimodular heterogeneous nuclear ribonucleoprotein
      (hnRNP) K protein with many of its protein and nucleic acid partners is regulated
      by extracellular signals. Acting as a docking platform, K protein could link
      signal-transduction pathways to DNA- and RNA-directed processes such as
      transcription, mRNA processing, transport, and translation. Treatment of
      hepatocyte culture with insulin increased K protein tyrosine phosphorylation.
      Insulin altered K protein interaction with RNA and DNA in vitro. Administration
      of insulin into mice had similar effects on K protein in liver.
      Coimmunoprecipitations of RNA with K protein revealed preferential in vivo K
      protein binding of a subset of transcripts, including the insulin-inducible c-fos
      mRNA. These results suggest a class of insulin pathways that signal nucleic acid
      directed processes that involve K protein.

PMID- 11470916
TI  - A glucose-responsive transcription factor that regulates carbohydrate metabolism
      in the liver.
AB  - Carbohydrates mediate their conversion to triglycerides in the liver by promoting
      both rapid posttranslational activation of rate-limiting glycolytic and lipogenic
      enzymes and transcriptional induction of the genes encoding many of these same
      enzymes. The mechanism by which elevated carbohydrate levels affect transcription
      of these genes remains unknown. Here we report the purification and
      identification of a transcription factor that recognizes the carbohydrate
      response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK)
      gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat
      livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding
      specificity in vitro precisely correlates with promoter activity in vivo.
      Furthermore, forced ChREBP overexpression in primary hepatocytes activates
      transcription from the L-type Pyruvate kinase promoter in response to high
      glucose levels. The DNA-binding activity of ChREBP can be modulated in vitro by
      means of changes in its phosphorylation state, suggesting a possible mode of
      glucose-responsive regulation. ChREBP is likely critical for the optimal long
      term storage of excess carbohydrates as fats, and may contribute to the imbalance
      between nutrient utilization and storage characteristic of obesity.

PMID- 11470917
TI  - Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the
      adenosine A1 receptor.
AB  - Caffeine is believed to act by blocking adenosine A(1) and A(2A) receptors
      (A(1)R, A(2A)R), indicating that some A(1) receptors are tonically activated. We
      generated mice with a targeted disruption of the second coding exon of the A(1)R
      (A(1)R(-/-)). These animals bred and gained weight normally and had a normal
      heart rate, blood pressure, and body temperature. In most behavioral tests they
      were similar to A(1)R(+/+) mice, but A(1)R(-/-) mice showed signs of increased
      anxiety. Electrophysiological recordings from hippocampal slices revealed that
      both adenosine-mediated inhibition and theophylline-mediated augmentation of
      excitatory glutamatergic neurotransmission were abolished in A(1)R(-/-) mice. In
      A(1)R(+/-) mice the potency of adenosine was halved, as was the number of A(1)R.
      In A(1)R(-/-) mice, the analgesic effect of intrathecal adenosine was lost, and
      thermal hyperalgesia was observed, but the analgesic effect of morphine was
      intact. The decrease in neuronal activity upon hypoxia was reduced both in
      hippocampal slices and in brainstem, and functional recovery after hypoxia was
      attenuated. Thus A(1)Rs do not play an essential role during development, and
      although they significantly influence synaptic activity, they play a nonessential
      role in normal physiology. However, under pathophysiological conditions,
      including noxious stimulation and oxygen deficiency, they are important.

PMID- 11470918
TI  - Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif
      recognition.
AB  - The Toll-like receptor (TLR) family consists of phylogenetically conserved
      transmembrane proteins, which function as mediators of innate immunity for
      recognition of pathogen-derived ligands and subsequent cell activation via the
      Toll/IL-1R signal pathway. Here, we show that human TLR9 (hTLR9) expression in
      human immune cells correlates with responsiveness to bacterial deoxycytidylate
      phosphate-deoxyguanylate (CpG)-DNA. Notably "gain of function" to
      immunostimulatory CpG-DNA is achieved by expressing TLR9 in human nonresponder
      cells. Transfection of either human or murine TLR9 conferred responsiveness in a
      CD14- and MD2-independent manner, yet required species-specific CpG-DNA motifs
      for initiation of the Toll/IL-1R signal pathway via MyD88. The optimal CpG motif
      for hTLR9 was GTCGTT, whereas the optimal murine sequence was GACGTT. Overall,
      these data suggest that hTLR9 conveys CpG-DNA responsiveness to human cells by
      directly engaging immunostimulating CpG-DNA.

PMID- 11470919
TI  - Elevated arginase I expression in rat aortic smooth muscle cells increases cell
      proliferation.
AB  - Arginase, which exists as the isoforms arginase I and II, catalyzes the
      hydrolysis of arginine to ornithine and urea. Ornithine is the principal
      precursor for production of polyamines, which are required for cell
      proliferation. Rat aortic smooth muscle cells (RASMC) contain constitutive
      arginase I, and arginase inhibitors cause inhibition of cell proliferation. The
      objective of this study was to determine whether the elevated expression of
      arginase I in RASMC causes increased cell proliferation. RASMC were stably
      transfected with either rat arginase I cDNA or a beta-galactosidase control
      expression plasmid. Western blots and arginase enzymatic assays revealed high
      level expression of cytosolic arginase I in arginase I-transfected RASMC.
      Moreover, this observation was associated with the increased production of urea
      and polyamines and higher rates of RASMC proliferation. The two selective
      inhibitors of arginase, N(G)-hydroxy-l-arginine and S-(2-boronoethyl)-l-cysteine,
      inhibited arginase and decreased the production of urea and polyamines in
      arginase I-transfected RASMC, all of which were associated with the inhibition of
      cell proliferation. This study demonstrates that elevated arginase I expression
      increases RASMC proliferation by mechanisms involving increased production of
      polyamines. These observations suggest that arginase I plays a potentially
      important role in controlling RASMC proliferation.

PMID- 11470920
TI  - Perforin-low memory CD8+ cells are the predominant T cells in normal humans that
      synthesize the beta -chemokine macrophage inflammatory protein-1beta.
AB  - The synthesis of antiviral beta-chemokines has joined cytolysis as a potential
      mechanism for the control of HIV-1 infection by CD8(+) T cells. Recent evidence
      suggests that these two effector functions can diverge in some individuals
      infected with HIV-1; however, little is known about the CD8(+) T cell subsets in
      normal individuals that synthesize antiviral beta-chemokines. In this report, we
      have used mutliparameter flow cytometry to characterize the T cell subsets that
      secrete the antiviral beta-chemokine macrophage inflammatory protein (MIP)-1beta.
      These studies have shown: (i) CD8(+) cells are the predominant T cell subset that
      synthesizes MIP-1beta; (ii) MIP-1beta and IFN-gamma are synthesized congruently
      in most CD8(+) T cells; however, significant numbers of these cells synthesize
      only one of these effector molecules; (iii) approximately 60% of the CD8(+) T
      cells that synthesize MIP-1beta lack perforin; (iv) MIP-1beta is synthesized with
      approximately equal frequency by CD28(+) and CD28(-) subpopulations of CD8(+) T
      cells; (v) MIP-1beta is synthesized by three distinct CD8(+) T cell subsets
      defined by the expression of CD45R0 and CD62L; and (vi) MIP-1beta is not
      synthesized in short-term cultures of naive CD8(+) T cells. These results
      demonstrate substantial subset heterogeneity of MIP-1beta synthesis among CD8(+)
      T cells and suggest that these subsets should be evaluated as correlates of
      protective immunity against HIV-1.

PMID- 11470921
TI  - A minimalist model protein with multiple folding funnels.
AB  - Kinetic and structural studies of wild-type proteins such as prions and
      amyloidogenic proteins provide suggestive evidence that proteins may adopt
      multiple long-lived states in addition to the native state. All of these states
      differ structurally because they lie far apart in configuration space, but their
      stability is not necessarily caused by cooperative (nucleation) effects. In this
      study, a minimalist model protein is designed to exhibit multiple long-lived
      states to explore the dynamics of the corresponding wild-type proteins. The
      minimalist protein is modeled as a 27-monomer sequence confined to a cubic
      lattice with three different monomer types. An order parameter-the winding index
      is introduced to characterize the extent of folding. The winding index has
      several advantages over other commonly used order parameters like the number of
      native contacts. It can distinguish between enantiomers, its calculation requires
      less computational time than the number of native contacts, and reduced
      dimensional landscapes can be developed when the native state structure is not
      known a priori. The results for the designed model protein prove by existence
      that the rugged energy landscape picture of protein folding can be generalized to
      include protein "misfolding" into long-lived states.

PMID- 11470922
TI  - Growth hormone interacts with the Marek's disease virus SORF2 protein and is
      associated with disease resistance in chicken.
AB  - Marek's disease (MD) is a lymphoproliferative disease of chickens induced by a
      herpesvirus, the MD virus (MDV). Because MD is a significant economic problem to
      the poultry industry, there is great interest in enhancing genetic resistance,
      which is controlled by multiple genes. The influence of the MHC has been clearly
      demonstrated, and several relevant quantitative trait loci have been mapped;
      however, no single gene influencing MD resistance has been identified.
      Transcription of SORF2 is perturbed in the MDV recombinant clone RM1 due to a
      solo insertion of the reticuloendotheliosis virus long terminal repeat, which may
      explain the loss of oncogenicity for this strain. Hypothesizing that SORF2
      interacting host proteins are involved in MD resistance, we screened a chicken
      splenic cDNA library by the yeast two-hybrid assay using SORF2 as bait. The
      chicken growth hormone (GH) structural peptide was identified, and the specific
      interaction was verified by coimmunoprecipitation. Immunohistochemical staining
      and indirect immunofluorescence assay indicated that GH and SORF2 can be
      coexpressed in MDV-infected cells both in vitro and in vivo. Furthermore,
      polymorphism in the GH gene (GH1) is associated with the number of tissues with
      tumors in commercial White Leghorn chickens with the MHC B*2/B*15 genotype. We
      conclude that GH1 may well be a MD resistance gene.

PMID- 11470923
TI  - Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine
      inhibitor.
AB  - Poxviruses express a family of secreted proteins that bind with high affinity to
      chemokines and antagonize the interaction with their cognate G protein-coupled
      receptors (GPCRs). These viral inhibitors are novel in structure and, unlike
      cellular chemokine receptors, are able to specifically interact with most, if not
      all, CC-chemokines. We therefore sought to define the structural features of CC
      chemokines that facilitate this broad-spectrum interaction. Here, we identify the
      residues present on human monocyte chemoattractant protein-1 (MCP-1) that are
      required for high-affinity interaction with the vaccinia virus 35-kDa CC
      chemokine binding protein (VV-35kDa). Not only do these residues correspond to
      those required for interaction with the cognate receptor CCR2b but they are also
      conserved among many CC-chemokines. Thus, the results provide a structural basis
      for the ability of VV-35kDa to promiscuously recognize CC-chemokines and block
      binding to their receptors.

PMID- 11470924
TI  - Presence of mitochondria-type ribosomes outside mitochondria in germ plasm of
      Drosophila embryos.
AB  - Mitochondrially encoded large and small ribosomal RNAs (mtlrRNA and mtsrRNA) are
      transported out of mitochondria to polar granules, the distinctive organelles of
      germ plasm in Drosophila. Reduction of the extramitochondrial mtlrRNA amount
      leads to the failure of embryos to form the germ-line progenitors, or pole cells,
      suggesting that mtlrRNA, along with mtsrRNA, functions on the polar granules to
      specify the germ line. In this study, we provide several lines of evidence
      showing that there are mitochondria-type ribosomes on the polar granules during a
      short period before pole cell formation. Our ultrastructural analysis reveals
      that these ribosomes include both mitochondrial rRNAs and at least two
      mitochondrial ribosomal proteins (S12 and L7/L12). Furthermore, these ribosomes
      are integrated into well developed polysomes on the surface of polar granules. We
      propose that translation dependent on mitochondria-type ribosomes is an important
      mechanism underlying germ-line formation.

PMID- 11470925
TI  - The mechanism of tryptophan induction of tryptophanase operon expression:
      tryptophan inhibits release factor-mediated cleavage of TnaC-peptidyl-tRNA(Pro).
AB  - Expression of the tryptophanase (tna) operon of Escherichia coli is regulated by
      catabolite repression and tryptophan-induced transcription antitermination. In a
      previous study, we reproduced the regulatory features of this operon observed in
      vivo by using an in vitro S-30 system. We also found that, under inducing
      conditions, the leader peptidyl-tRNA (TnaC-peptidyl-tRNA(Pro)) is not cleaved; it
      accumulates in the S-30 reaction mixture. In this paper, we examine the
      requirements for TnaC-peptidyl-tRNA(Pro) accumulation and cleavage, in vitro. We
      show that this peptidyl-tRNA remains bound to the translating ribosome. Removal
      of free tryptophan and addition of release factor 1 or 2 leads to hydrolysis of
      TnaC-peptidyl-tRNA(Pro) and release of TnaC from the ribosome-mRNA complex.
      Release factor-mediated cleavage is prevented by the addition of tryptophan. TnaC
      of the ribosome-bound TnaC-peptidyl-tRNA(Pro) was transferable to puromycin. This
      transfer was also blocked by tryptophan. Tests with various tryptophan analogs as
      substitutes for tryptophan revealed the existence of strict structural
      requirements for tryptophan action. Our findings demonstrate that the addition of
      tryptophan to ribosomes bearing nascent TnaC-peptidyl-tRNA(Pro) inhibits both
      TnaC peptidyl-tRNA(Pro) hydrolysis and TnaC peptidyl transfer. The associated
      translating ribosome therefore remains attached to the leader transcript where it
      blocks Rho factor binding and subsequent transcription termination.

PMID- 11470926
TI  - Vitamin A and the developing embryo.

PMID- 11470927
TI  - Familiar drugs may prevent cancer.
AB  - Despite positive results in large scale chemoprevention trials, many physicians
      are unaware of the potential cancer preventive properties of drugs in common
      usage. The antioestrogen tamoxifen and the selective cyclo-oxygenase-2 inhibitor
      celecoxib have been licensed in the USA for the chemoprevention of breast and
      colorectal cancers respectively in selected high risk individuals. Similarly,
      folate and retinol have been shown to decrease the incidence of colorectal cancer
      and squamous cell carcinoma of the skin respectively in large scale intervention
      trials. Other retinoids have proved efficacious in the tertiary chemoprevention
      of cancers of the breast and head/neck. Epidemiological evidence also exists in
      favour of aspirin, non-steroidal anti-inflammatory drugs, and angiotensin
      converting enzyme inhibitors preventing certain cancers. Phytochemicals may
      represent less toxic alternatives to these agents. Although some of these drugs
      are available without prescription and most are not yet licensed for use in
      cancer chemoprevention, physicians and students of medicine should be aware of
      this accumulating evidence base. Practitioners should be amenable to patient
      referral to discuss complex issues such as risk estimation or potential benefit
      from intervention.

PMID- 11470928
TI  - Update on chronic viral hepatitis.
AB  - Many recent and significant advances in the field of chronic viral hepatitis,
      including therapy, suggest that an update on chronic hepatitis is timely. Chronic
      hepatitis B virus infection remains a significant worldwide cause of liver
      cirrhosis and hepatocellular carcinoma, despite the wide availability of a long
      established and effective vaccine. Transmission occurs via perinatal, sexual, and
      parenteral routes (particularly intravenous drug abuse and although blood
      products still carry a risk, this is now extremely low in Western countries).
      Only a minority of infected adult cases develop chronic hepatitis but in children
      under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic
      liver injury ranges from mild inflammation to end stage liver cirrhosis.
      Interferon alfa has been the mainstay of treatment for patients with active
      disease but nucleoside analogues (lamivudine and adefovir) are now available with
      similar efficacy. Patients with end stage liver disease and hepatocellular
      carcinoma can be offered transplantation but infection in the graft is
      commonplace. The combination of hepatitis B immunoglobulin and newer antiviral
      drugs reduce the incidence and severity of graft infection significantly. The
      hepatitis C virus epidemic of the latter half of the 20th century now affects
      more than 1% of populations worldwide. This RNA virus is spread parenterally and
      is becoming the leading indication for liver transplantation. The majority of
      patients develop chronic hepatitis, which may be progressive, evolving to
      significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20%
      cases after decades. Treatment with the combination of interferon alfa and
      ribavirin is successful in up to 40% cases. Liver transplantation is a
      therapeutic option for some but graft infection is universal and often
      complicated by progressive liver fibrosis. A vaccine remains a remote prospect so
      that prevention is crucial. Hepatitis D virus infection occurs on a background of
      hepatitis B virus infection and can also cause liver damage. The response to
      antiviral therapy is poor. The newer "hepatitis" viruses G and TT do not cause
      significant liver injury.

PMID- 11470929
TI  - Pharyngeal pouch (Zenker's diverticulum).
AB  - Pharyngeal pouches occur most commonly in elderly patients (over 70 years) and
      typical symptoms include dysphagia, regurgitation, chronic cough, aspiration, and
      weight loss. The aetiology remains unknown but theories centre upon a structural
      or physiological abnormality of the cricopharyngeus. A diagnosis is easily
      established on barium studies. Treatment is surgical via an endoscopic or
      external cervical approach and should include a cricopharyngeal myotomy.
      Unfortunately pharyngeal pouch surgery has long been associated with significant
      morbidity, partly due to the surgery itself and also to the fact that the
      majority of patients are elderly and often have general medical problems.
      External approaches are associated with higher complication rates than endoscopic
      procedures. Recently, treatment by endoscopic stapling diverticulotomy has
      becoming increasingly popular as it has distinct advantages, although long term
      results are not yet available. The small risk of developing carcinoma within a
      pouch that is not excised remains a contentious issue and is an argument for long
      term follow up or treating the condition by external excision, particularly in
      younger patients.

PMID- 11470930
TI  - Ethical, professional, and legal obligations in clinical practice: a series of
      discussion topics for postgraduate medical education. Topic 5: disclosing
      confidential information.

PMID- 11470931
TI  - Adrenal myelolipoma.

PMID- 11470932
TI  - Consultations and referrals for dyspepsia in general practice--a one year
      database survey.
AB  - OBJECTIVE: Dyspepsia usually presents first in primary care. There are many
      reasons for referral including urgent problems (for example, haematemesis and
      melaena), treatment failure, or to exclude serious pathology. Referral will
      change the population characteristics of primary and secondary care dyspeptics.
      Many of the guidelines for primary care dyspepsia, however, are based on
      secondary care research on these referred patients. The aim of this study was to
      describe the prevalence of dyspepsia in general practice, the characteristics of
      patients presenting with dyspepsia in primary care, and the clinical and non
      clinical determinants of referral in these patients. DESIGN: Cross sectional
      survey of the consultation records of patients presenting with dyspepsia in
      primary care during a one year period. METHODS: Dyspeptic patients who consulted
      their general practitioner (GP) in 1997 were selected on the basis of
      International Classification of Primary Care codes using a computer search among
      20 sentinel practices affiliated with the Utrecht Network of General
      Practitioners. Cross tables and logistic regression analysis were carried out to
      reveal patient characteristics and determinants of referral. RESULTS: The
      prevalence of dyspepsia presenting in primary care in 1997 was 3.4% (1740/48958).
      These patients were usually not referred during the first consultation. Men,
      elderly patients, and patients with a previous history of dyspepsia were referred
      to secondary care more frequently than other dyspeptic patients. Patients
      diagnosed with both irritable bowel syndrome and dyspepsia were at risk of being
      referred most. CONCLUSION: Dyspepsia is a frequently occurring complaint in
      primary care and patients are usually treated by their GP. Besides clinically
      relevant reasons for referral, dyspeptic patients with irritable bowel syndrome
      seem to be more "at risk" of being referred to secondary care than other
      dyspeptic patients. The differences between primary and secondary care dyspeptic
      patients should be taken into account when interpreting research for guideline
      purposes. Further research is needed to clarify the background of the relation
      between irritable bowel syndrome and dyspepsia and its influence on referral.

PMID- 11470933
TI  - A study of bone densitometry in patients with complex regional pain syndrome
      after stroke.
AB  - INTRODUCTION: This study was undertaken to evaluate the bone mineral density
      (BMD) in patients with complex regional pain syndrome type-I (CRPS-I) after
      stroke, and to correlate it with various clinical and neurophysiological
      parameters. PATIENTS AND METHODS: Twenty patients with CRPS-I after stroke were
      included and a detailed neurological evaluation was carried out. The severity of
      CRPS-I was graded on the basis of shoulder hand syndrome score. All the patients
      underwent bone mineral densitometry of paralysed and non-paralysed forearm by
      dual energy x ray absorptiometry. The BMD of paralysed forearm was also compared
      with that of age matched healthy controls. Neurophysiological tests included
      sympathetic skin response in both upper and lower limbs and median somatosensory
      evoked potentials. RESULTS: The mean age of patients was 57.2 (45-75) years and
      eight were females. Eight patients had severe weakness and 12 had moderate
      weakness of grade 2 on the hemiplegic side. There was significant reduction in
      BMD in the patients compared with controls (p<0.01). The bone density reduction
      correlated well with duration of illness (r = -0.673, p<0.01), shoulder hand
      syndrome score (r = -0.804, p<0.01), and Canadian neurological scale score (r = 
      0.738 p<0.01). Sympathetic skin response was not recordable bilaterally in all
      patients. Median somatosensory evoked potentials were not recordable in seven out
      of 20 patients who also had higher grade of CRPS-I. CONCLUSION: Our results show
      significant reduction of BMD in patients with CRPS-I after stroke. The reduction
      in BMD correlates with the severity of shoulder hand syndrome score, degree of
      weakness, duration of hemiplegia, and the severity of stroke.

PMID- 11470934
TI  - Mitochondrial cytopathy presenting with focal segmental glomerulosclerosis,
      hypoparathyroidism, sensorineural deafness, and progressive neurological disease.
AB  - A 6 year old boy who presented with steroid unresponsive nephrotic syndrome is
      reported. He was found to have focal segmental glomerulosclerosis and associated
      hypoparathyroidism and sensorineural deafness. The child progressed to end stage
      renal failure and was successfully managed by dialysis and cadaveric renal
      transplantation. He later developed progressive neurological deterioration and
      mitochondrial myopathy and neuropathy was diagnosed.

PMID- 11470935
TI  - A new variant of Carney's triad: phaeochromocytoma and chondrosarcoma.
AB  - A 61 year old hypertensive woman presented in 1986 with a right scapular
      chondrosarcoma. She developed type 1 diabetes mellitus in 1991 and suffered a
      stroke in 1991. Chest radiography showed pulmonary metastases in 1997. Further
      radiological staging detected a right sided phaeochromocytoma, which was
      subsequently removed in 1998. Before this, repeated urine estimations of
      vanillylmandelic acid had been normal. Her diabetes was cured by adrenalectomy.
      It is believed that the combination of phaeochromocytoma and extrapulmonary
      chondrosarcoma represents a new variant of Carney's triad.

PMID- 11470936
TI  - Generalised oedema, lethargy, personality disturbance, and recurring nightmares
      in a young girl.

PMID- 11470937
TI  - An unusual pituitary mass presenting with panhypopituitarism and hyponatraemia.

PMID- 11470938
TI  - A Mauritian woman with fever, abdominal pain, and facial palsy.

PMID- 11470939
TI  - Hyperplastic polyposis coli associated with dysplasia.

PMID- 11470940
TI  - Confusion in an elderly patient: an uncommon diagnosis for such a common event.

PMID- 11470941
TI  - Siblings with multiple soft tissue calcifications.

PMID- 11470942
TI  - A man with a murmur requiring nutritional support.

PMID- 11470943
TI  - Heart failure, a thick tongue, and an abnormal cranial computed tomogram.

PMID- 11470944
TI  - Massive pleural effusion.

PMID- 11470953
TI  - Acute hepatocellular and cholestatic injury in a patient taking celecoxib.
AB  - A case of acute hepatocellular and cholestatic liver injury that may have been
      associated with the use of celecoxib is described. This case was reported to US
      Food and Drug Administration and the manufacturer of celecoxib.

PMID- 11470957
TI  - Alpha-synuclein and the Lewy body disorders.
AB  - alpha-Synuclein has risen to prominence during the past 5 years because of its
      association with several neurodegenerative diseases that have come to be known as
      the synucleinopathies. The clinical phenotype of the synucleinopathies is
      variable, with the most common being parkinsonism, autonomic dysfunction, and
      dementia. Progress has been made in clinical, neuropathologic and biochemical
      characterization of the synucleinopathies and their differentiation from other
      neurodegenerative disorders. At the molecular level, the synucleinopathies have
      conformational and post-translational modifications of synuclein that favor its
      fibrillization and aggregation in inclusions in neurons and glia. Whether
      inclusion body formation is an adaptive response or is directly related to
      degeneration of neuronal and glial cells is a topic of current research.

PMID- 11470958
TI  - The genetics of late-onset Alzheimer's disease.
AB  - Of late-onset Alzheimer's disease patients 50% do not carry an apolipoprotein E
      epsilon 4 allele, indicating that there must be other genetic or environmental
      risk factors for the disease. During the past few years, both genetic linkage and
      candidate gene studies have been undertaken in order to identify novel genetic
      risk factors for late-onset Alzheimer's disease. Previous genome screens
      implicated a region of chromosome 12 that contains the genes that encode both
      alpha(2)-macroglobulin and the low-density lipoprotein receptor-related protein.
      However, candidate gene studies have produced mixed results with respect to both
      of these genes. New linkage studies now provide strong evidence for Alzheimer's
      disease susceptibility loci on chromosomes 9 and 10. The locus on chromosome 10
      very probably modifies risk for Alzheimer's disease by modulating beta-amyloid-42
      levels.

PMID- 11470959
TI  - Progress in the modeling of neurodegenerative diseases in transgenic mice.
AB  - Transgenic mouse models exist for the major neurodegenerative diseases, including
      Alzheimer's disease, tauopathy and amyotrophic lateral sclerosis. Although many
      of the mice do not completely replicate the human disease they are intended to
      model, they have provided insight into the mechanisms that underlie disease
      etiology. In the case of the Alzheimer's disease and amyotrophic lateral
      sclerosis models, the mice have also provided a therapeutic testing ground for
      the testing of agents that have been shown to have considerable clinical promise.

PMID- 11470960
TI  - Learning and memory: recent findings.
AB  - Recent findings from neuroimaging, event-related potential and lesion
      investigations reflect a rapidly emerging view that the memory system is widely
      distributed throughout the cortex. It is clear that the pattern of cortical
      involvement during encoding and retrieval of memories is critically dependent on
      the nature and complexity of task demands. This has implications, both for
      existing models of memory function, and in the methodology of future
      investigations and the issues they address. No consensus has yet been reached on
      a number of issues, perhaps most notably the role of the hippocampus in
      retrieval, but advances in measurement techniques should enable some of these
      matters to be resolved. Further work must address the complex dynamics of the
      memory system, the extent to which the same regions underlie different functions,
      and how different regions interact and reflect common functions.

PMID- 11470961
TI  - Recent advances in hereditary spastic paraplegia.
AB  - The hereditary spastic paraplegias are a group of rare disorders that are
      characterized by great clinical and genetic heterogeneity. There has been an
      exponential increase in the number of HSP loci mapped in recent years, with nine
      out of the 17 loci reported during the past 2 years. Eight loci have now been
      identified for the autosomal-dominant form, and seven of these are associated
      with pure HSP. Spastic paraplegia-4 remains the most frequent locus, and is
      usually associated with a pure phenotype. Although the corresponding spastin gene
      was only recently identified, over 50 mutations have been described to date,
      which renders molecular diagnosis difficult. Five loci are known for autosomal
      recessive HSP, and four of these are associated with complex forms, all with
      different phenotypes. Two genes have been identified: paraplegin and sacsin.
      Finally, three loci have been identified in X-linked HSP, two of which are
      complex forms. The genes that encode L1 and PLP were the first to be identified
      in HSP disorders. Surprisingly, the five genes encode proteins of different
      families, making understanding and diagnosis of HSP even more difficult. The
      discovery of new genes should hopefully help to clarify the pathophysiology of
      these disorders.

PMID- 11470962
TI  - Depression in Parkinson's disease.

PMID- 11470963
TI  - Dystonia: an update on genetics and treatment.
AB  - Recent years have seen many advances in our understanding of the genetics of the
      dystonias, with 13 loci identified to date. The DYT1 gene, which causes most
      cases of childhood-onset generalized primary dystonia, was cloned in 1997, and
      use of cell models has begun to unravel the role of its protein (torsinA) in both
      health and disease. Treatment of more severe dystonia has been a difficult area,
      with only limited success from medical therapies. Recently, there has been
      increasing interest in the use of globus pallidus deep brain stimulation and a
      number of reports have shown promising results.

PMID- 11470964
TI  - Parkin and Parkinson's disease.
AB  - Parkin is the causative gene for an autosomal recessive form of Parkinson's
      disease. The gene was discovered in 1998. The parkin gene is a novel gene
      containing 12 exons spanning over 1.5 Mb and encodes a protein of 465 amino acids
      with a molecular mass of approximately 52,000 M(r). Various deletion mutations
      and point mutations have been discovered in patients with autosomal recessive
      Parkinson's disease. The substantia nigra and the locus coeruleus selectively
      undergo neurodegeneration without forming Lewy bodies. The parkin gene product,
      Parkin protein, has a unique structure with a ubiquitin-like domain in the amino
      terminus and a RING finger motif in the carboxy terminus. The function of Parkin
      was not known until recently. During the year 2000, great progress was made in
      defining its function. First of all, Parkin was found to be a ubiquitin-protein
      ligase (E3), a component of the ubiquitin system, which is an important adenosine
      triphosphate-dependent protein degradation machinery. In addition, CDCrel-1, a
      synaptic vesicle associated protein, was found to be a substrate for Parkin as an
      E3. Although many studies still need to be performed to elucidate the molecular
      mechanism of the selective nigral neurodegeneration in this form of familial
      Parkinson's disease, it will not be too long before this is accomplished. In this
      review article, we evaluate the developments in this area published since 1
      February 2000.

PMID- 11470965
TI  - The role of glial cells in Parkinson's disease.
AB  - Parkinson's disease is a common neurodegenerative disorder characterized by the
      progressive loss of the dopaminergic neurons in the substantia nigra pars
      compacta. The loss of these neurons is associated with a glial response composed
      mainly of activated microglial cells and, to a lesser extent, of reactive
      astrocytes. This glial response may be the source of trophic factors and can
      protect against reactive oxygen species and glutamate. Aside from these
      beneficial effects, the glial response can mediate a variety of deleterious
      events related to the production of reactive species, and pro-inflammatory
      prostaglandin and cytokines. This article reviews the potential protective and
      deleterious effects of glial cells in the substantia nigra pars compacta of
      Parkinson's disease.

PMID- 11470966
TI  - Recent advances in the understanding of tau protein and movement disorders.
AB  - Tau plays an important role in movement disorders. The accumulation of
      pathological tau is a major substrate of frontotemporal dementia and parkinsonism
      linked to chromosome 17, progressive supranuclear palsy, and corticobasal
      degeneration. Over the past year, several new mutations on the tau gene have been
      found. These mutations have been classified into three groups: (i) mutations in
      constitutively spliced exons; (ii) mutations in the alternatively spliced exon
      10; and (iii) mutations of the exon 10 5' splice site. Some patients presenting
      with frontotemporal dementia and parkinsonism linked to chromosome 17 transiently
      respond to levodopa therapy. The significance of Pick bodies was recognized by a
      recent study on kindred with the Glu342Val tau mutation. In sporadic cases of
      progressive supranuclear palsy, the presence of the H1 haplotype was found to be
      a risk factor. Corticobasal degeneration shares a common genetic background with
      progressive supranuclear palsy. This opens the question of whether corticobasal
      degeneration represents a separate disorder or a spectrum of disease with
      progressive supranuclear palsy. However, distinguishing features are observed,
      and include oculomotor abnormalities, which may help to differentiate these two
      disorders on clinical grounds. Despite recent advances in the understanding of
      the tauopathies, there are still no curative therapies available. It is hoped
      that studies in transgenic tau animal models will lead to the development of
      successful treatments.

PMID- 11470967
TI  - Management of psychosis in Parkinson's disease.
AB  - Psychosis is quite common in Parkinson's disease (approximately 25% of patients)
      and therefore constitutes a serious public health problem. All patients suffering
      from idiopathic Parkinson's disease, and especially elderly and demented
      patients, are at risk of developing delusions or hallucinations. The most
      prominent psychotogenic factors are dopaminomimetic agents, which may induce
      dopamine hypersensitivity in the frontal and limbic dopamine projection regions,
      and consequently, either directly or indirectly, elicit psychotic signs and
      symptoms. A Parkinson's disease-related cholinergic deficit in combination with
      an age-related further loss of cholinergic integrity also plays a prominent role.
      Psychosis in Parkinson's disease patients appears to be a more important
      contributor to caregiver distress than motor parkinsonism. Psychosis therefore
      probably represents the single greatest risk factor for nursing home placement.
      Typical antipsychotic drugs, because of their selective dopamine receptor
      antagonistic effects, can reduce psychotic signs but at the cost of an increase
      in parkinsonism. As a consequence of a non-selective antagonism at both
      serotonergic and dopaminergic receptors, atypical antipsychotic drugs are
      associated with fewer extrapyramidal side-effects. On the other hand,
      hypersensitivity to these agents may induce delirium or a malignant neuroleptic
      syndrome. Atypical antipsychotic agents such as clozapine, quetiapine and
      olanzapine should therefore be started at very low doses that are increased
      gradually. Cholinomimetic therapy may prove to be helpful in the prevention and
      treatment of psychotic manifestations in Parkinson's disease patients, given the
      effects observed in patients suffering from dementia with Lewy bodies.

PMID- 11470968
TI  - Autonomic dysfunction in movement disorders.
AB  - Dysfunction of the autonomic nervous system is an under-recognised but important
      aspect of the aetiological and clinical manifestation of primary degenerative
      dysautonomias such as multiple system atrophy (MSA) and Parkinson's disease (PD).
      Although the clinical presentation of dysautonomia in these two disorders may
      overlap, yet pathological and in vivo imaging studies suggest considerable
      differences. Functional imaging studies suggest that selective cardiac
      sympathetic denervation may occur early in PD but not in other parkinsonian
      syndromes. The clinical implication of this apparently disease specific
      peripheral dysautonomia is unknown and would be the subject of much interest in
      future years. Dysautonomia in degenerative disorders also affect respiration,
      genitourinary function and sleep. Sleep related disorders such as rapid eye
      movement behaviour disorder and urinary voiding dysfunction appear to precede the
      development of PD related symptoms while patients with sporadic ataxia have been
      shown to progress to develop MSA. Dysautonomia has also been recognised in other
      movement disorders, examples being the combination of dystonia and complex
      regional pain syndrome with elevated HLA-DR13 and late onset Huntington's disease
      presenting with dominant parkinsonism and minimal chorea. These studies have
      helped progress in various diagnostic and management parameters in relation to
      autonomic dysfunction and movement disorders.

PMID- 11470969
TI  - The many faces of transforming growth factor-beta in pleural diseases.
AB  - Transforming growth factor (TGF)-beta is responsible for critical regulatory
      functions in many physiologic and pathologic processes. Emerging evidence
      suggests that these roles also apply to a multitude of pleural diseases. Both
      mesothelial cells and infiltrating cells in the pleural space can produce
      TGFbeta, and elevated TGFbeta concentrations have been found in pleural effusions
      and in pleural tissues during disease processes. Recent animal studies have
      suggested that TGFbeta can induce significant pleurodesis and probably plays a
      central role in the pathogenesis of pleural fibrosis. Paradoxically, TGFbeta may
      also stimulate increased pleural fluid formation, in part by inducing the
      production of vascular endothelial growth factor. TGFbeta also participates in
      the regulation of pleural inflammation and cell proliferation. Further research
      into the roles of TGFbeta in the pathogenesis of various pleural diseases is
      needed and may lead to the development of novel treatment strategies.

PMID- 11470970
TI  - Normal volume and cellular contents of pleural fluid.
AB  - The pleural space in healthy humans was thought to contain a few milliliters of
      fluid, based on extrapolation from animal studies. However, because of the
      obvious technical difficulties in atraumatically retrieving such a small volume
      of fluid, the exact volume and cellular content of human pleural fluid has not
      been known. Development of a minimally invasive pleural lavage technique has
      allowed, for the first time, the measurement of volume and cellular content of
      the pleural fluid in healthy humans.

PMID- 11470971
TI  - Cholesterol in the separation of transudates and exudates.
AB  - The Light criteria represent the most acceptable method to separate transudates
      and exudates. However, approximately 10% of patients with transudates, especially
      those with congestive heart disease, are misdiagnosed with these criteria. To
      improve diagnostic accuracy, many biochemical markers have been proposed as
      alternatives to differentiate transudates and exudates. Cholesterol has raised
      particular interest because only pleural fluid is needed, which makes blood
      samples unnecessary and simplifies the procedure. In most clinical studies,
      cholesterol has been shown to be as sensitive as the Light criteria, although it
      is less specific. Other randomized studies are necessary to determine the real
      potential value of pleural-fluid cholesterol measurements. Studies of pleural
      fluid cholesterol are aimed at better understanding the mechanisms by which
      cholesterol enters the pleural cavity and its role in diseases. The ideal cutoff
      point of cholesterol to differentiate transudates and exudates is still unknown.
      Recently, aspects of the cholesterol turnover in diseases have raised great
      interest. Cholesterol generated great interest after it was related to coronary
      artery diseases. The involvement of cholesterol in the atherosclerotic process is
      well known, although its importance in body cavities is still unclear.

PMID- 11470972
TI  - Immunohistochemical differential diagnosis of pleural effusions, with emphasis on
      malignant mesothelioma.
AB  - The immunohistochemical diagnosis of atypical epithelial proliferations in
      pleural fluid is a challenging topic in cytopathology and surgical pathology.
      Mesothelioma may be simulated clinically and radiologically by several other
      nonneoplastic and neoplastic disorders, mandating that strict histologic,
      histochemical, immunohistochemical, and ultrastructural guidelines be followed
      for its diagnosis. Because of its availability to most laboratories,
      immunohistochemistry has emerged as the most commonly used procedure for the
      diagnosis of pleural malignancies. This review considers the current status of
      that investigative modality, with particular attention to lesions that are
      suspected to be mesothelial.

PMID- 11470973
TI  - Management of parapneumonic pleural effusion.
AB  - Parapneumonic pleural effusion is a common and potentially serious complication
      of pneumonia. The management of parapneumonic pleural effusion involves early
      diagnosis, adequate empiric antibiotic cover, and appropriate risk
      categorization. High-risk patients require safe and expedient drainage of the
      infected pleural space. The management options include thoracentesis, tube
      thoracostomy, adjunctive intrapleural fibrinolytic therapy, and surgical
      drainage. The methods of surgical drainage include thoracoscopy, thoracotomy, and
      decortication. The relative clinical efficacy of these treatment options has been
      studied in a small number of controlled clinical trials, the results of which
      have been systematically reviewed by expert panels. Based on the limited clinical
      evidence, expert reviewers were unable to recommend a best method of pleural
      drainage. However, the consensus is that an aggressive approach with early
      surgical drainage results in shorter hospital stays and may be more cost
      effective than conservative management. This review discusses the clinical
      evidence and describes an aggressive sequential management strategy that combines
      intrapleural fibrinolysis with early surgical drainage.

PMID- 11470974
TI  - Pleural effusion due to pulmonary emboli.
AB  - Pulmonary embolism is the fourth leading cause of pleural effusion. The
      possibility of pulmonary embolus should be evaluated for all patients who have
      undiagnosed pleural effusion. The mechanism of pleural effusion caused by
      pulmonary embolus is usually increased interstitial fluid in the lungs as a
      result of ischemia or the release of vasoactive cytokines. Approximately 75% of
      patients with pulmonary emboli and pleural effusion have pleuritic chest pain.
      The most common cause of pleuritic chest pain and pleural effusion in patients
      under 40 years old is pulmonary emboli. Pleural effusion resulting from a
      pulmonary embolus usually occupies less than one-third of the hemithorax. Dyspnea
      is frequently out of proportion to the size of the pleural effusion. Pleural
      fluid caused by pulmonary emboli is usually exudative but is occasionally
      transudative. d-Dimer testing is a good screen for pulmonary emboli. If d-dimer
      results are positive, then a spiral computed tomograph should be obtained to
      confirm the diagnosis. Low-molecular-weight-heparin has become the initial
      treatment of choice for patients with pulmonary emboli and pleural effusion.

PMID- 11470975
TI  - Pleural effusions and pneumothoraces in AIDS.
AB  - Pneumothorax occurs in 1 to 2% of hospitalized patients with HIV and is
      associated with 34% mortality. Pneumocystis carinii pneumonia and chest
      radiographic evidence of cysts, pneumatoceles, or bullae are risk factors for
      spontaneous pneumothorax. Tube thoracostomy, pleurodesis, and surgical treatment
      are usually needed to manage spontaneous pneumothorax in AIDS. Pleural effusion
      is seen in 7 to 27% of hospitalized patients with HIV infection. Its three
      leading causes are parapneumonic effusions, tuberculosis, and Kaposi sarcoma.
      Pleural effusions occur in 15 to 89% of cases of pulmonary Kaposi sarcoma and in
      68% of cases of thoracic non-Hodgkin lymphoma in patients with AIDS. Primary
      effusion lymphoma accounts for 1 to 2% of non-Hodgkin lymphomas. Kaposi sarcoma
      and primary effusion lymphoma are associated with human herpesvirus 8. The
      prognosis of patients with pleural Kaposi sarcoma and non-Hodgkin lymphoma in
      AIDS is poor, and the major goal of treatment is palliation.

PMID- 11470976
TI  - Thoracoscopy in the management of pneumothorax.
AB  - Spontaneous pneumothorax is a common condition that impacts significantly on
      healthcare expenditure. However, optimal management of spontaneous pneumothorax
      remains a subject of considerable controversy. A thoracic surgeon's perspective
      on the use of thoracoscopy and video-assisted thoracic surgery with a focus on
      surgical techniques in the current management of this condition is presented.

PMID- 11470978
TI  - Occupational and environmental causes of bronchogenic carcinoma.
AB  - Occupational and environmental carcinogens account for an important minority of
      cases of bronchogenic carcinoma. From a public health perspective, it is
      important to characterize occupational and environmental carcinogens and to
      define disease risk to reduce preventable lung cancer. From a clinician's
      perspective, it is important to distinguish individual cases of occupational lung
      cancer from nonoccupational cases, because cancer acquired from work may be
      compensable through worker's compensation claims and litigation. Important
      carcinogens include asbestos, radon daughters, diesel exhaust, and metals.
      Epidemiologic investigations identify excess cases of lung cancer in populations
      exposed to carcinogens. Experimental animal and ex vivo human research provide
      complementary information supporting causal relationships between exposure and
      carcinogenesis. Clinical challenges include proving that a given case of lung
      cancer is due to an occupational exposure. Research challenges include
      determining safe exposure thresholds. Only a small percentage of all chemicals
      used in industry have been extensively analyzed for their carcinogenic potential.
      Scientific and regulatory information about pulmonary occupational and
      environmental health and safety is available from several important agencies and
      organizations, including the Occupational Safety and Health Administration, the
      National Institute for Occupational Safety and Health, the International Agency
      for Research on Cancer, the American Lung Association, and the Environmental
      Protection Agency.

PMID- 11470979
TI  - Mediastinal tumors.
AB  - Mediastinal tumors are comprised of various benign and malignant neoplasms that
      share the same anatomic location within the thorax. The mediastinum is
      traditionally divided into three compartments: the anterior, middle, and
      posterior mediastinum. This division, based on lateral chest radiographs, helps
      clinicians establish appropriate differential diagnoses and plan further imaging,
      diagnostic, and treatment strategies. With the continued and complex advances in
      imaging, medical treatment, and surgery, we recommend a multidisciplinary
      approach to the management of mediastinal tumors. This discussion is intended to
      guide the pulmonary specialist through this potentially complex approach.

PMID- 11470980
TI  - Unusual primary lung neoplasms.
AB  - Bronchial carcinoids and hamartomas are, respectively, the most common malignant
      and benign unusual primary lung neoplasms. These tumors are often asymptomatic
      but can cause central airway obstruction. Helical computed tomographic and
      radionuclide scintigraphic advances in their detection and evolution, together
      with newer interventional bronchoscopy techniques such as neodymium:yttrium
      aluminum-garnet laser phototherapy and cryotherapy, represent important
      improvements in the diagnosis and management of patients with such tumors.

PMID- 11470981
TI  - Solitary pulmonary nodules: new wine in old bottles.
AB  - Management strategies for solitary pulmonary nodules have evolved slowly during
      the last 50 years. The goal has always been to facilitate the resection of
      malignant nodules without undue delay and to avoid exploratory thoracotomy for
      benign nodules. In the past decade, the development of reliable nodule
      enhancement techniques has replaced or become incorporated within some of the
      older strategies. In addition, some of the well-accepted concepts of the past
      have been undergoing critical reviews and reevaluations. These concepts include
      retrospective study of nodule diameters to recognize 2-year stability, the use of
      a watch-and-wait strategy using standard chest radiographs for prospective
      determination of stability, detection and recognition of calcification patterns
      on standard chest radiographs, and computed tomography for mediastinal staging.

PMID- 11470982
TI  - Management of patients with advanced non-small-cell lung cancer.
AB  - Lung cancer is one of the most lethal cancers, causing more deaths of men and
      women than any other cancer in the United States. Non-small-cell lung cancers
      account for most the newly diagnosed cases of lung cancer. Many patients with non
      small-cell lung cancer present with advanced-stage disease and are not
      appropriate candidates for combined modality therapy. Although these patients
      have incurable disease, they have a chance of achieving improved 1-year survival
      rates and palliation of symptoms with chemotherapy. The performance status of
      patients with advanced non-small-cell lung cancer is the most important
      determinant of response to chemotherapy.

PMID- 11470983
TI  - Brain abscess due to Listeria monocytogenes: five cases and a review of the
      literature.

PMID- 11470984
TI  - Intraabdominal infection due to Streptococcus pneumoniae.

PMID- 11470985
TI  - Epidemiologic and clinical characteristics of Bartonella quintana and Bartonella
      henselae endocarditis: a study of 48 patients.

PMID- 11470986
TI  - Cryoglobulinemia: study of etiologic factors and clinical and immunologic
      features in 443 patients from a single center.

PMID- 11470987
TI  - Chronic severe uveitis: etiology and visual outcome in 927 patients from a single
      center.

PMID- 11470988
TI  - The HLA-DRB1*0401 allele and the development of methotrexate-induced accelerated
      rheumatoid nodulosis: a follow-up study of 79 Caucasian patients with rheumatoid
      arthritis.

PMID- 11470989
TI  - Trauma Care 2002-Scandinavia.

PMID- 11470991
TI  - N-Acetyltransferases, sulfotransferases and heterocyclic amine activation in the
      breast.
AB  - Heterocyclic amines are mammary carcinogens in rats and their N-hydroxy
      metabolites are substrates for subsequent metabolic activation by N
      acetyltransferases (NAT) and sulfotransferases (SULT) in man. We investigated the
      expression of these enzymes in human breast tissue and the relationship between
      NAT genotype and NAT mRNA expression or enzyme activity. Immunohistochemical
      staining of sections of breast tissue identified expression of NAT1 and NAT2
      protein in human mammary epithelial cells, but not in the stroma. We also
      measured the formation of DNA adducts of the heterocyclic amines 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine in calf thymus DNA after incubation of their promutagenic N-hydroxy
      metabolites with mammary cytosols prepared from reduction mammoplasty tissue.
      Experimental observations gained from use of enzyme cofactors and NAT and/or SULT
      inhibitors on cytosolic enzyme activity, recombinant NAT1 activity and
      heterocyclic amine-DNA adduct formation suggest that both NAT1 and SULT1A enzymes
      contribute significantly to the activation of N-hydroxylated heterocyclic amines
      in mammary tissue. NAT1 mRNA transcript levels were found to be two- to three
      fold higher than mRNA transcripts of the NAT2 gene in reduction mammoplasty
      tissue and mammary epithelial cells. NAT1-specific p-aminobenzoic acid
      acetylation activity, but not NAT2-specific sulfamethazine acetylation activity,
      was detectable in mammary cytosols. There was no association apparent between NAT
      genotype and the levels of NAT mRNA or NAT enzyme activity, or between NAT1
      genotype and IQ-DNA adduct formation mediated by mammary cytosols. Western blot
      analysis of mammary cytosolic protein showed detectable levels of SULT1A1 and
      SULT1A3.

PMID- 11470992
TI  - Modulation of DNA and protein adducts in smokers by genetic polymorphisms in
      GSTM1,GSTT1, NAT1 and NAT2.
AB  - The formation of DNA and protein adducts by environmental pollutants is modulated
      by host polymorphisms in genes that encode metabolizing enzymes. In our study on
      67 smokers, aromatic-DNA adduct levels were examined by nuclease P1 enriched 32P
      postlabelling in mononuclear blood cells (MNC) and 4-aminobiphenyl-haemoglobin
      adducts (4-ABP-Hb) by gas chromatography-mass spectroscopy. Genetic polymorphisms
      in glutathione S-transferase M1 (GSTM1), T1 (GSTT1) and N-acetyl-transferase 1
      (NAT1) and 2 (NAT2) were assessed by polymerase chain reaction-based methods. DNA
      adduct levels, adjusted for the amount of cigarettes smoked per day, were higher
      in GSTM1(-/-) individuals (1.30 +/- 0.57 adducts per 108 nucleotides) than in
      GSTM1(+) subjects (1.03 +/- 0.56, P = 0.05), higher in NAT1 slow acetylators
      (1.58 +/- 0.54) than in NAT1 fast acetylators (1.11 +/- 0.58, P = 0.05) and were
      also found to be associated with the NAT2 acetylator status (1.29 +/- 0.64 and
      1.03 +/- 0.46, respectively, for slow and fast acetylators, P = 0.06). An effect
      of GSTT1 was only found in combination with the NAT2 genotype; individuals with
      the GSTT1(-/-) and NAT2-slow genotype contained higher adduct levels (1.80 +/-
      0.68) compared to GSTT1(+)/NAT2 fast individuals (0.96 +/- 0.36). Highest DNA
      adduct levels were observed in slow acetylators for both NAT1 and NAT2 also
      lacking the GSTM1 gene (2.03 +/- 0.17), and lowest in GSTM1(+) subjects with the
      fast acetylator genotype for both NAT1 and NAT2 (0.91 +/- 0.45, P = 0.01). No
      overall effects of genotypes were observed on 4-ABP-Hb levels. However, in
      subjects smoking less than 25 cigarettes per day, 4-ABP-Hb levels were higher in
      NAT2 slow acetylators (0.23 +/- 0.10 ng/g Hb) compared to fast acetylators (0.15
      +/- 0.07, P = 0.03). These results provide further evidence for the combined
      effects of genetic polymorphisms in GSTM1, GSTT1, NAT1 and NAT2 on DNA and
      protein adduct formation in smoking individuals and indicate that, due to the
      complex carcinogen exposure, simultaneous assessment of multiple genotypes may
      identify individuals at higher cancer risk.

PMID- 11470993
TI  - Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression
      and function in human liver.
AB  - The human cytochrome P450, CYP2B6, is involved in the metabolism of several
      therapeutically important drugs and environmental or abused toxicants. In this
      study, we present the first systematic investigation of genetic polymorphism in
      the CYP2B6 gene on chromosome 19. A specific direct sequencing strategy was
      developed based on CYP2B6 and CYP2B7 genomic sequence information and DNA from 35
      subjects was completely analysed for mutations throughout all nine exons and
      their exon-intron boundaries. A total of nine novel point mutations were
      identified, of which five result in amino acid substitutions in exon 1 (C64T,
      Arg22Cys), exon 4 (G516T, Gln172His), exon 5 (C777A, Ser259Arg and A785G,
      Lys262Arg) and exon 9 (C1459T, Arg487Cys) and four are silent mutations (C78T,
      G216C, G714A and C732T). Polymerase chain reaction-restriction fragment length
      polymorphism tests were developed to detect each of the five nonsynonymous
      mutations in genomic DNA. By screening a population of 215 subjects the C64T,
      G516T, C777A, A785G and C1459T mutations were found at frequencies of 5.3%,
      28.6%, 0.5%, 32.6% and 14.0%, respectively. Haplotype analysis revealed six
      different mutant alleles termed CYP2B6*2 (C64T), *3 (C777A), *4 (A785G), *5
      (C1459T), *6 (G516T and A785G) and *7 (G516T, A785G and C1459T). By analysing a
      large number of human liver samples, significantly reduced CYP2B6 protein
      expression and S-mephenytoin N-demethylase activity were found in carriers of the
      C1459T (R487C) mutation (alleles *5 and *7). These data demonstrate that the
      extensive interindividual variability of CYP2B6 expression and function is not
      only due to regulatory phenomena, but also caused by a common genetic
      polymorphism.

PMID- 11470994
TI  - Characterization of the CYP2D6*29 allele commonly present in a black Tanzanian
      population causing reduced catalytic activity.
AB  - Debrisoquine metabolism among Tanzanians has been found to be slower than
      expected from the CYP2D6 genotype. In order to evaluate any genetic explanation,
      the coding sequence and intron-exon boundaries of the CYP2D6 gene from three
      Black Tanzanian volunteers with a CYP2D6*1/*1 or CYP2D6*2/*2 genotype and
      debrisoquine metabolic ratios (MRs) > 1 were fully sequenced to screen for new
      mutations. Two functional mutations, G1747 to A (causing V136I) and G3271 to A
      (causing V338M), were identified in the CYP2D6*2/*2 sample. Thirty-six subjects
      (34%) out of a total 106 subjects were heterozygous and three subjects (3%) were
      homozygous for the allele, yielding an allele frequency of 20%. The CYP2D6*29
      allele, having also the mutations of the CYP2D6*2 allele, was subsequently
      expressed in yeast and mammalian COS-1 cells. No differences were seen with
      respect to the affinity (Km) or maximal velocity (Vmax) of the CYP2D6 substrate
      bufuralol between the wild-type and mutant when expression was carried out in
      yeast cells. By contrast, the 1'-hydroxybufuralol catalytic activity of the
      mutant expressed in COS-1 cells was only 26% of the wild-type (P < 0.01; Mann
      Whitney U-test) and its debrisoquine hydroxylation activity was 63% of that of
      CYP2D6.1. The single mutants V136I and V338M had reduced capacity for bufuralol
      hydroxylation, but the effect was even stronger when both mutations were present
      together as in CYP2D6.29. Analysis of the distribution of CYP2D6*29 in subjects
      phenotyped for debrisoquine revealed that this allele significantly causes a
      reduction in the rate of debrisoquine hydroxylation in vivo. The results indicate
      the common existence in Tanzanians of a variant CYP2D6 form with different
      substrate specificity as compared to the wild-type form of the enzyme causing
      reduced capacity for debrisoquine metabolism.

PMID- 11470995
TI  - Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and
      C734A polymorphisms of human CYP1A2.
AB  - Either G-2964 or A734 in the human CYP1A2 gene was confirmed to be associated
      with high inducible enzyme activity in smokers, but not in nonsmokers. In this
      study, for the first time, we observed an association between phenotypes and
      genotypes of CYP1A2 with respect to the two genetic polymorphisms in 163 healthy
      Chinese volunteers living in Qidong. The ratio of plasma 17X/137X at 6 h after
      oral administration of 300 mg caffeine was employed in CYP1A2 phenotyping
      analysis, while genotyping analysis was carried out by polymerase chain reaction
      restriction fragment length polymorphism. The allele frequencies of A at -2964
      and A at 734 in 139 non-smoking subjects were 0.25 and 0.67, respectively. The
      A/A-2964C/C734, G/A-2964C/C734 or A/A-2964C/A734 genotype that was thought to
      have lower inducibility/activity of CYP1A2 than the other genotypes did not exist
      in the tested Chinese subjects. The ratio of 17X/137X was 0.46 +/- 0.26 in G/G
      2964A/A734 genotypes (n = 22) and 0.36 +/- 0.19 in non-G/G-2964A/A734 (n = 117).
      In addition, there was significant difference between them (P = 0.036). A similar
      result was also achieved in 24 smokers. Since Qidong is a special region with
      particularly high incidence of hepatocellular carcinoma in China, the association
      of phenotypes with genotypes of CYP1A2 in the Qidong population might result from
      some inducible environmental factors such as those of cigarettes in smokers.

PMID- 11470996
TI  - Glutathione S-transferase genotypes and allergic responses to diisocyanate
      exposure.
AB  - Diisocyanates are the most common low molecular weight chemicals to cause
      occupational asthma. However, only some 5-10% of exposed workers develop asthma,
      which suggests an underlying genetic susceptibility. Diisocyanates and their
      metabolites may be conjugated with glutathione by glutathione S-transferases
      (GSTs). We examined whether polymorphisms in the GSTM1, GSTM3, GSTP1 and GSTT1
      genes modify allergic responses to diisocyanate exposure. The study population
      consisted of 182 diisocyanate exposed workers, 109 diagnosed with diisocyanate
      induced asthma and 73 without asthma. Lack of the GSTM1 gene (null genotype) was
      associated with a 1.89-fold risk of diisocyanate-induced asthma [95% confidence
      interval (CI) 1.01-3.52]. Moreover, among the asthma patients, the GSTM1 null
      genotype was associated with lack of diisocyanate-specific immunoglobulin (Ig)E
      antibodies [odds ratio (OR) 0.18, 95% CI 0.05-0.61] and with late reaction in the
      specific bronchial provocation test (OR 2.82, 95% CI 1.15-6.88). Similarly, GSTM3
      AA genotype was related to late reaction in the specific bronchial provocation
      test (OR 3.75, 95% CI 1.26-11.2). The GSTP1 Val/Val genotype, on the other hand,
      was related to high total IgE levels (OR 5.46, 95% CI 1.15-26.0). The most
      remarkable effect was seen for the combination of GSTM1 null and the GSTM3 AA
      genotype which was strongly associated with lack of diisocyanate-specific IgE
      antibodies (OR 0.09, 95% CI 0.01-0.73) and with late reaction in the bronchial
      provocation test (OR 11.0, 95% CI 2.19-55.3). The results suggest, for the first
      time, that the polymorphic GSTs, especially the mu class GSTs, play an important
      role in inception of ill effects related to occupational exposure to
      diisocyanates.

PMID- 11470997
TI  - Identification and functional characterization of eight CYP3A4 protein variants.
AB  - The genetic component of the inter-individual variability in CYP3A4 activity has
      been estimated to be between 60% and 90%, but the underlying genetic factors
      remain largely unknown. A study of 213 Middle and Western European DNA samples
      resulted in the identification of 18 new CYP3A4 variants, including eight protein
      variants. A total of 7.5% of the population studied was found to be heterozygous
      for one of these variants. In a bacterial heterologous expression system, two
      mutants, R130Q and P416L, did not result in detectable P450 holoprotein. One
      mutant, T363M, expressed at significantly lower levels than wild-type CYP3A4.
      G56D, V170I, D174H and M445T were not significantly different when compared with
      wild-type CYP3A4 in expression or steroid hydroxylase activity. L373F displayed a
      significantly altered testosterone metabolite profile and a four-fold increase in
      the Km value for 1'-OH midazolam formation. The results suggest a limited
      contribution of CYP3A4 protein variants to the inter-individual variability of
      CYP3A4 activity in Caucasians. Some variants may, however, play a role in the
      atypical response to drugs or altered sensitivity to carcinogens.

PMID- 11470998
TI  - Testing drug response in the presence of genetic information.

PMID- 11471000
TI  - [Should surgeons get involved in research?].

PMID- 11471001
TI  - [Peroperative exploration of the liver in hepatic tumor surgery].
AB  - Intraoperative exploration of the liver and complete abdominal examination are
      essential before hepatic resection for patients with liver tumors. The surgeon's
      eye and hand, traditional methods of exploration, are still accurate for
      abdominal exploration, screening of small superficial liver tumors and evaluation
      of non-tumoral liver parenchyma. Intraoperative ultrasonography is often superior
      to preoperative screening methods in diagnosing small liver tumors.
      Intraoperative ultrasonography identifies variations of intrahepatic vascular
      structures and reveals exact location of tumors according to functional anatomy.
      The surgeon's eye and hand and intraoperative ultrasound are complementary for a
      complete exploration, and may affect operative decision making. Laparoscopy and
      laparoscopic ultrasonography, when diagnosing non resectable tumors, reduce the
      number of unnecessary laparotomies. However, the effectiveness of exploration by
      laparoscopy and laparoscopic ultrasonography is lower than that of laparotomy,
      which remains indispensable before hepatic resection for malignant tumors.

PMID- 11471002
TI  - [Diagnosis of appendicular syndromes: for a rational approach].
AB  - Diagnosis of acute appendicitis is made in 80% of cases by analysis of symptoms
      and physical examination. Epigastric pain, secondary located in the lower
      quadrant, along with tenderness is the most specific sign of acute appendicitis.
      In 20% of cases, diagnosis is difficult. High level of leucocytosis is not of
      great value. Laparoscopy has been proposed to visualize the appendix.
      Echotomography and tomodensitometry are less invasive and less costly procedures,
      that let surgeons identify the appendix and confirm or reject the diagnosis of
      acute appendicitis. Thus, surgical acts should be restricted to necessary
      appendicectomies.

PMID- 11471004
TI  - [Liver transplantation for alcoholic liver disease].
AB  - Alcoholic cirrhosis is a major public health issue in France. The prevalence of
      alcoholic cirrhosis and the number of potential candidates for liver
      transplantation is unknown but certainly underestimated. Despite physicians'
      ethical reserves concerning this self-inflicted disease and the public's
      misgivings, liver transplantation for alcoholic cirrhosis can provide survival
      rates comparable with those observed for other chronic liver diseases. in this
      indication, liver transplantation if often associated with a low risk of acute
      rejection and a high rate cancer of the upper respiratory and digestive tracts.
      The risk of recurrent alcoholism after liver transplantation is also a major
      problem. Its prevalence varies from 10 to 50%, depending on the assessment
      criteria, and the rate recurrent risk for the liver graft (alcohol intake>40 g/d)
      is to the order of 10%. These figures illustrate the importance of careful
      management and support for these patients. At least 6 months weaning from alcohol
      is a commonly accepted selection criterion for transplantation candidates.
      Criteria for liver transplantation generally include patients aged under 65
      years, weaned for more than 6 months, with Child C cirrhosis or less,
      uncontrollable digestive tract hemorrhage, spontaneous severe infection,
      hepatorenal syndrome, hepatopulmonary syndrome, or multifocal hepatocellular
      carcinoma if the largest nodule measures less than 3 cm. Acute alcoholic
      hepatitis is a severe disease, fatal in 50% of the cases, and resistant tot
      corticosteroid therapy. Liver transplantation in this subpopulation of often
      young patient who have not achieved weaning merits further evaluation.

PMID- 11471005
TI  - [Perineal rectosigmoid resection for exterior rectal prolapse (Altemeier
      operation)].

PMID- 11471006
TI  - [The rectal advancement flap].

PMID- 11471007
TI  - [Fundamental digestive tract sutures].

PMID- 11471008
TI  - [Traumatic perforation of the duodenum].

PMID- 11471009
TI  - [Acute pancreatitis. Conclusions and recommendations of the jury - short text].

PMID- 11471010
TI  - [A 59-year-old woman admitted for hematemesis].

PMID- 11471012
TI  - [The sequence of the human PrP gene Exon I and its upstream segment has promoter
      like activity].
AB  - OBJECTIVE: The human PrP gene locates at the short-arm of the 20th chromosome.
      This article is was to map the promoter that transcribes the human PrP gene.
      METHODS: The sequence of the human PrP gene Exon I and its upstream segment were
      amplified using PCR, and inserted into a CAT reporter plasmid pBL-CAT6 after
      sequence analysis. The values of the relative CAT expression under the control of
      this fragment were evaluated after transiently transfected into HeLa, COS7 and Sh
      sy5y cell lines. The amounts of transcription activator SP1 in these three cell
      lines were calculated with band-shift assays. RESULTS: Analysis of the human PrP
      gene Exon I and its upstream segment showed a GC rich sequence, with several
      potential SP1 binding sites, but without any TATA-box. Under the control of this
      fragment, the CAT expressions were 2-3 folds increased in transient transfection.
      Quantity band-shift assays revealed that SP1 was enriched in HeLa cells, but
      undetectable in COS7 and Sh-sy5y cells. CONCLUSIONS: The sequence of the human
      PrP gene Exon I and its upstream segment functions as a promoter-like sequence,
      probably being as a weak TATA-less promoter. Cells derived from different tissues
      contain different amount of SP1. The activity of this promoter-like sequence
      seems to be independent of SP1 presence.

PMID- 11471013
TI  - [Expression and characterization of human vascular endothelial growth factor in
      Pichia pastoris].
AB  - OBJECTIVE: To study the expression of human VEGF165 cDNA in Pichia pastoris and
      to obtain high-level expression of recombinant human VEGP165 (hVEGF165) with good
      biological activity. METHODS: Amplifying hVEGF165 cDNA by PCR, after confirmed by
      DNA sequence analysis, the gene was inserted into the Pichia pastoris expression
      vector pPIC9K containing AOX1 promoter and a secreting signal peptides, the
      recombinant expression plasmid pPIC9K/VEGF165 was constructed and transformed
      into KM71. The multiple insert transformants were screened, fermented in flasks
      and induced by 1% methanol. RESULTS: After 4 days of methanol induction, the
      expressed hVEGF165 came up to 30% of total proteins in supernatant by SDS-PAGE.
      The expressed hVEGF165 was further proved having good antigenicity and high
      specificity by ELISA and Western blot assay, and having good biological activity
      to stimulate HUVEC proliferation. CONCLUSIONS: High-level expression of secreted
      hVEGF165 had been successfully achieved in Pichia pastoris expression system.

PMID- 11471014
TI  - [Human Fab antibodies derived from phage display library neutralize hepatitis A
      virus in vitro].
AB  - OBJECTIVE: Development of recombinant human monoclonal antibody to hepatitis A
      virus as a emergent measure for prevention of hepatitis A virus infection.
      METHODS: Human neutralizing monoclonal antibody Fab fragments to HAV have been
      developed by using phage display technique. The heavy and light chains of human
      IgG Fab genes were amplified from a HAV patient in convalescent stage. The
      combinatorial phage antibody library was established by inserting both heavy and
      light chains of Fab genes into phage mid-vector pComb3 and followed by help phage
      infection after 4 rounds of panning with purified HAV as coated antigen. RESULTS:
      The human Fab fragments to HAV were selected and expressed in bacteria.
      CONCLUSIONS: The specific binding of Fab antibodies to HAV were demonstrated by
      their reaction with HAV antigen in ELISA. These results provide the basis for
      further development of a neutralizing recombinant human whole IgG molecule and
      hold promise for future use in the prophylaxis of HAV infection.

PMID- 11471015
TI  - [Discovery of a new subtype of SEO virus].
AB  - OBJECTIVE: The M and S segments of Cou3, a Hantavirus strain isolated from Rattus
      norvegieus were partially reverse transcripted, PCR amplified and sequenced with
      ABI 373 DNA sequencer to observe the differences from other SEO type viruses.
      METHODS: RT-PCR was used to amplify M and S segments of Cou3 strain, and then the
      nucleotide (nt) sequences of the segments were analysed. Phylogenetic tree
      analysis was also performed. RESULTS: The different property through PCR
      amplification and partial nucleotide sequence data showed that Gou3 was a
      Hantavirus of SEO type with significance difference from the other SEO type
      viruses. The nt sequence homology between Cou3 and the other SEO type viruses was
      only about 85%, but the deduced amino acid (aa) sequence of partial glycoprotein
      was highly conservative, at least as same as that among the other SEO type
      viruses. Sequence analysis also showed that nt or aa sequence homology between
      Gou3, or other SEO type, and HTN type viruses was nearly the same, while the
      phylogenetic tree analysis showed that Gou3 was a virus which was between HTN and
      the other SEO type viruses but closer to the latter. CONCLUSIONS: Gou3 is a SEO
      virus but belongs to a new subtype.

PMID- 11471016
TI  - [Construction and expression of recombinant adeno-associated HIV -1 virus].
AB  - OBJECTIVE: Plasmid of AAV vector with HIV-1 gag and gp 120 were constructed
      respectively. METHODS: The recombinant AAV-HIV gag and gp120 viruses were
      obtained by co transfection of AAV-HIV plasmid and Adenovirus 5 in 293 cells.
      RESULTS: The recombinant AAV-HIV virus expressed well and the titer of the
      recombinant viruses were between 10(4)-10(5). CONCLUSIONS: The recombinant AAV
      HIV virus can be used to infect the target cells for detection of cellular
      immunity and for vaccine studies.

PMID- 11471017
TI  - [Rapid detection of drug resistant HIV -1 to reverse transcriptase and protease
      inhibitors in HIV-infected patients receiving highly active antiretroviral
      therapies].
AB  - OBJECTIVE: To develop and validate a rapid and sensitive method that can be used
      to detect emergence of HIV-1 drug resistant viruses in HIV-infected patients
      receiving highly active antiretroviral therapies (HAART). METHODS: HIV-1 viral
      RNA was extracted from plasma and amplified by nested RT-PCR. Nucleotide
      sequences of the reverse transcriptase (RT) and protease (PR) genes were
      determined by automated DNA sequencing. RESULTS: RT and PR sequences can be
      reliably determined with a minimum 2,000 copies/ml of viral RNA in plasma.
      Emergence of drug resistant viruses can he detected as soon as it reached to >
      25% of the total viral populations. By using this method, drug-resistant viral
      populations were found to correlate with rebound of viral RNA level after
      prolonged antiretroviral therapies in HIV-infected children. CONCLUSIONS: This
      rapid and sensitive HIV-1 genotyping method can be used to predict and confirm
      emergence of HIV-1 drug resistance in HIV-infected patients receiving HAART.

PMID- 11471018
TI  - [Molecular epidemiology analysis of HIV-1 subtype E strains found in Shenzhen,
      China].
AB  - OBJECTIVE: To investigate the prevalent status of HIV-1 subtype E epidemic among
      different populations in Shenzhen, China. METHODS: HIV-1 proviral DNA from
      peripheral blood mononuclear cells (PBMCs) of 3 HIV-infected individuals found in
      Shenzhen was amplified by nested-PCR. The C2-V3 and its flanking region (350-450
      nucleotides) of HIV- 1 env gene were sequenced directly from the PCR products and
      analysed. RESULTS: These 3 cases were confirmed to be infected with HIV-1 subtype
      E strain (sz-E). The innergroups distance of sz-E was 2.6%. In comparison with
      the consensus sequence of international A-E subgroups and some of subtype B
      epidemic in China, the genetic distances among sz-E and each of A-D subgroups and
      some of subtype B were more than 24 %. Furthermore, the phylogenetic tree
      analysis showed that sz-E clustered closely to Econ. CONCLUSIONS: These findings
      suggested that the epidemic time for HIV-1 subtype E, which was mainly prevalent
      among IDUs population and some professional blood donors, had been about 2-3
      years in Shenzhen.

PMID- 11471019
TI  - [Research of status of provirus HIV DNA in non-progressor and progressor of HIV-1
      infected persons].
AB  - OBJECTIVE: This study was designed to investigate the different status of
      provirus HIV DNA in non-progressor and progressor of HIV-1 infected persons.
      METHODS: HIV RNA, HIV DNA were detected with long-distance PCR (LD-PCR), reverse
      transcription PCR (RT-PCR), Southern blot and molecular hybridization from plasma
      and peripheral blood mononuclear cells (PBMCs), using primers locating between
      long terminal repeats LTR(U5)-LTR(R) and so on. RESULTS: 9.1 kb band is full
      length HIV DNA genome which was present in all templates of 12 progressors.
      Deleted HIV DNA was observed in 9 of 12 progressors. Both the full-length and
      defective. provirus HIV DNA was detected in 5 of the 18 non-progressors.
      Defective HIV DNA was only detected in the other non-progressors. CONCLUSIONS:
      Clinical stages are closely related with both the full-length and the defective
      HIV DNA.

PMID- 11471020
TI  - [Epitope mapping of HIV-1 using phage-display random peptide library and the
      purified IgG from HIV patient].
AB  - OBJECTIVE: By using phage display random peptide library, the B cell epitope of
      HIV protein was studied. METHODS: The library displaying random dodecamers was
      biopanned first with human total IgG antibodies against HIV-1, and then non
      specific phages were subtracted by purified IgG from non-HIV sera. After three
      rounds of screening, the positive phages were tested by ELISA for their
      reactivity with HIV(+)-IgG and HIV(-)-IgG antibodies. Phage that showed positive
      reactivity with HIV(+)-IgG, but negative to HIV(-)-IgG, were selected and their
      displayed peptides were determined by DNA sequencing. RESULTS: All the 13
      positive clones sequenced displayed five kinds of peptides (SPKCLGKLLCAF,
      THQCLGKLQCGV, SCSAKFTCTTQI, KSDCSARFMCSV, DCLKQWACEWSR) that have homology to the
      HIV-I gp4l (602GCSGKLICTIN613). CONCLUSIONS: This method demonstrated there is a
      dominant epitope in the region of HIV-1 gp4l and can be used in the research of
      the B cell epitope of HIV protein.

PMID- 11471021
TI  - [Expression of Epstein-Barr virus latent membrane protein 2 in murine fibroblasts
      by retroviral-mediated gene transfer].
AB  - OBJECTIVE: This study is to find an efficient way to express EB virus latent
      membrane protein 2 in mammalian cells, and provide for further investigate on the
      function of LMP2 protein and its role in cellular immunity. METHODS: The LMP2
      gene was cloned into the EcoR I site of a retroviral vector LXSN and the
      recombinant LXSN-LMP2 was transfected into PT67 by lipofect TAMINE. After
      screened by G418, the supernatant of G418-resistant cells was used to infect
      murine fibroblasts NIH 3T3 to determine the virus titer. DNA was extracted from
      transfected cells and tested by PCR. Indirect immunofluorescence assay was used
      to detect the expression of the inserted gene. RESULTS: The virus titer was 5.8 x
      10(5) PFU/ml. The result of PCR showed that the LMP2 gene had been integrated
      into the DNA of transfected cells. Indirect immunofluorescence showed that the
      LMP2 gene had been expressed in the murine fibroblasts. CONCLUSIONS: EB virus
      LMP2 gene had been integrated into the genome of cells by retroviral-mediated
      transfer and the target gene had been expressed.

PMID- 11471022
TI  - [The study on relation of human papillomavirus and P53 expression with bladder
      transitional cell carcinoma].
AB  - OBJECTIVE: To study the relationship between the bladder transitional cell
      carcinoma and the human papillomavirus (HPV) types 6, 11, 16, 18 and P53.
      METHODS: We used polymerase chain reaction (PCR) to test HPV type 6, 11, 16 and
      18 infection from 75 cases of bladder cancer, and used immunohistochemistry
      method to detect P53 expression. RESULTS: The positive rates of HPV types 6, 11,
      16 and 18 were 6.7%, 5.3%, 33.3% and 6.7%, respectively. The positive rate of low
      risk HPV type (6/11) was 9.3% (7/75), and that of high risk HPV types (16/18) was
      34.7% (26/75). There were 8 cases with two or three HPV types mixed infection,
      accounting for 10.6%, HPV types 6,11,16,18 in tumor metastasis group were
      significantly higher than that in non-metastasis group. The positive rates of HPV
      16, 18 types in G3 were significantly higher than that in G1 and G2. HPV type 16
      was the main type in bladder cancer. Positive rate of P53 expression was 44%.
      CONCLUSIONS: These results implicated that the occurrence and development of
      bladder transitional cell carcinoma may be closely related to the high risk HPV
      type infection and P53 expression.

PMID- 11471023
TI  - [The study of immune effect of nine kinds of recombinant hepatitis B vaccines
      made in China and foreign countries].
AB  - OBJECTIVE: To study the immune effect of nine kinds of recombinant hepatitis B
      (FIB) vaccines. METHODS: Immunizing 715 primary school children with four
      genetically engineered FIB vaccines of 12 batches that were yeast HB vaccine
      (YDV), Chinese hamster ovary cell HB vaccine (CHO), vaccinia derived vaccine and
      Hansenula Polymorpha vaccine produced by USA MSD Co, USA Amgen Co, Japan, France,
      Argentina and Beijing, Changchun, Shenzhen of China. The anti-HBs was tested by
      RIA (Abbott reagent). RESULTS: Four kinds of genetically engineered HB vaccines
      were safe and effective. The peak of the antibody after immunization with Chinese
      vaccines appeared at the 7th month of the first dose. The geometric mean titre
      (GMT) of the anti-HBs was higher (393.60 mIU/ml) after immunized by vaccinia
      derived vaccine, its stability was better than the batches of CHO. The antibody
      titer descended in a narrow range after immunization of YDV. The vaccine
      containing 10 microg/dose was superior to 5 microg/dose in antibody persistence.
      Hansenuly polymorpha vaccine was the first time to study in China, it showed a
      good immune effect. CONCLUSIONS: The total immune effect of the recombinant FIB
      vaccines made no distinction among the products of China and USA, Japan, France
      and Argentina.

PMID- 11471024
TI  - [Study of relativity between HBV M and HBV DNA in the cases with hepatitis B].
AB  - OBJECTIVE: Serum samples of 414 cases with hepatitis B were detected for
      hepatitis B markers (HBV M) and HBV DNA, in order to investigation the
      relationship between HBV M and HBV DNA, and its clinical significant. METHODS:
      HBV M and HBV DNA were detected by ELISA and blot hybridization methods
      respectively. RESULTS: HBV DNA positive rates in the groups of acute and chronic
      hepatitis B were higher than that in the group of liver cirrhosis (P <0.01); HBV
      DNA positive rates had no apparent difference between the HBsAg, HBeAg, anti-HBc
      positive group and the HBsAg, anti-HBs, anti-HBc positive group. Direct
      relativity was shown between the titer of HBsAg and/or HBeAg and the positive
      rate of HBV DNA. CONCLUSIONS: HBV DNA can be treated as a sign of HBV activity;
      the appearance of anti-HBs can not be taken as indicator of ceasing of HBV
      replication; the changes in HBsAg and HBeAg titers may be used as clinical
      evaluation on HBV replication and index for anti-viral therapeutic effect.

PMID- 11471025
TI  - [A preliminary study on the activation of superoxide dismutase by Tiopronin in
      patients with chronic hepatitis B].
AB  - OBJECTIVE: To observe the clearance effect of Tiopronin on oxygen free radicals
      in chronic hepatitis B patients. METHODS: The ranthine oxidase assay was used to
      detect superoxide dismutase (SOD) in 80 chronic hepatitis B patients, the ALT,
      TBil, TP and AIG ratio of the patients were also tested. The 80 chronic hepatitis
      B patients were divided into two groups, the control group was treated with
      routine liver protective and jaundice regressing drugs while the treated group
      was additionally administered with Tiopromin besides the routine treatment.
      RESULTS: In two groups of patients with similar ages and sexes, there showed no
      differences in levels of SOD, ALT, TBil, TP and ALB before treatment, as the SOD
      in treated group and control group were 106.57 (40.68 NU/ml and 105.18(44.59
      NU/ml respectively, while the normal value for SOD in 16 normal persons was
      165.9(23.36 NU/ml. After treatment, there were significant differences (P< 0.01)
      in SOD, ALT, TBil and ALB levels which showed SOD 187.93(35.24 NU/ml, ALT
      38.41(22.22 U/L, TBil 23.15(12.46 micromol/L, ALB 43.28 (4.21 g/L in the treated
      group and SOD 157.96(47.29 NU/ml, ALT 68.52(34.19 U/L, TBil 30.38(21.80
      micromol/L and ALB 40.36(5.19 g/L in the control group. CONCLUSIONS: There showed
      a good therapeutic effect of Tiopronin on the clearance of oxygen free radicals
      in chronic hepatitis B patients and also it can improve the liver function.

PMID- 11471026
TI  - [Preliminary study on pathogenicity of hepatitis G virus].
AB  - OBJECTIVE: To study the clinical, enzymatic and liver pathological changes in
      patients with hepatitis G virus (HGV) infection. METHODS: RT- nested PCR was
      applied to detect HGV RNA in 368 patients with hepatic diseases. The liver biopsy
      tissue from one liver cirrhosis patient with simple HGV infection was examined.
      RESULTS: Simple HGV RNA positive were found in 7 cases of 71 acute hepatitis
      jaundice, in 22 cases of 155 chronic hepatitis and in 3 cases of 51 liver
      cirrhosis. The immunohistochemistry of the liver biopsy tissue from a liver
      cirrhosis patient showed HGV NS5 antigen positive. However, HGV infection might
      occur simply or in combination with hepatitis B or C virus or super infected.
      CONCLUSIONS: HGV RNA could be detected in acute hepatitis jaundice, chronic
      hepatitis, hepatitis B or C carriers, liver cirrhosis and hepatocellular
      carcinoma. HGV is proved to be a hepatotropic virus by pathological examination
      and immunohistochemistry, the virus located in the cytoplasm of the liver cells.
      It may cause chronic hepatitis and even liver cirrhosis, so HGV is pathogenic to
      liver tissue.

PMID- 11471027
TI  - [Study on the correlation of clinical features, pathology and
      immunohistochemistry of single HGV infection].
AB  - OBJECTIVE: Our objective is to study the pathogenicity of the single HGV
      infection. METHODS: The ELISA was used to check the serum anti-HGV antibody of 36
      cases. Immunohistochemistry staining of hepatic tissue was conducted by using HGV
      NS5 McAb in 20 single HGV infected patients who were further confirmed by
      clinical diagnosis and pathological evidence. These patients included 10 cases of
      acute hepatitis, 7 cases of chronic hepatitis, 1 cases of subacute severe
      hepatitis and 2 cases of chronic severe hepatitis. RESULTS: (1) Clinical
      manifestation: Acute hepatitis occurred abruptly, accompanied with fever,
      inertia, nausea and sometimes with vomiting and oil disgust. Chronic hepatitis
      developed slowly and presented mild symptoms. Severe hepatitis presented an acute
      onset, extreme fatigue, serious gastrointestinal symptoms, or even hepatic coma
      developed. (2) Changes of ALT and AST: ALT and AST increased slightly in chronic
      hepatitis and moderately in acute and severe hepatitis. The disproportion between
      ALT and BiL sometimes occurred in severe hepatitis. (3) Pathological changes in
      hepatic tissue: Acute hepatitis was characterized by hepatocyte swelling and
      inflammatory cells infiltrated in portal duct areas. Chronic hepatitis was
      identified by hepatocyte swelling, piecemeal necrosis or spotty necrosis, slight
      infiltration of inflammatory cell in portal duct areas and fibrosis. Severe
      hepatitis appeared as hepatic cell necrosis, inflammatory cell infiltration and
      slight fibrosis. CONCLUSIONS: Infection of HGV can give rise to acute hepatitis,
      chronic hepatitis and severe hepatitis.

PMID- 11471028
TI  - [Study of ADRV antibody persistence in the serum of ADRV positive cases].
AB  - OBJECTIVE: This research aimed at observing the persistent time of ADRV antibody
      in the sera of ADRV cases. METHODS: We adopted a sensitive and specific Enzyme
      linked immunosorbent assay (ELISA) for detecting ADRV antibody in patients who
      had recovered. RESULTS: We tested 260 human sera from Yi-Ma town of Henan
      Province. One year, six years and ten years after the patients had recovered, the
      of positive rates for ADRV antibody were respectively 27.7%, 36.3% and 23.3%.
      Thirty subjects of ADRV antibody positive were followed up retrospectively, no
      recurrent diarrhea was found. CONCLUSIONS: The ADRV antibody can last 16 years
      after primary infection.

PMID- 11471029
TI  - [Sequence analysis of phosphoprotein genes of respiratory syncytial virus field
      strains isolated in China].
AB  - OBJECTIVE: To get information about phosphoprotein (P) genes of RSV field strains
      isolated in China. METHODS: The complete nucleotide sequences of the P protein
      genes from six respiratory syncytial virus strains were determined with cDNA
      clones which had been amplified by RT-PCR and cloned into PTZ18R plasmid vector
      and compared with those of previously published counterparts of A2 and CH18537
      strains. RESULTS: The data indicated that there had high identities (>95%) at
      nucleotide and amino acid levels among the strains within the same subgroup;
      there were more divergence among strains (<85%) from different subgroups at
      nucleotide and amino acid levels of P genes, especially in the 3'-noncoding
      regions and the divergent domains. The analysis of hydrophobicity indicated that
      there had difference from 50 to 100 amino acid of P proteins between A and B
      subtypes. CONCLUSIONS: The analysis of the P genes confirm that there existed
      variability among RSV field strains and strains A2 and CH18537. The data
      described above revealed the characteristics of the P genes of RSV field strains
      isolated in China.

PMID- 11471030
TI  - [Detection of Coxsackie B virus IgM antibody in myocarditis patients by Mac
      ELISA].
AB  - OBJECTIVE: To detect Coxsackie B virus type 1-6 IgM antibodies from 193
      clinically diagnosed myocarditis cases. METHODS: The capture IgM ELISA (Mac
      ELISA) test was used. RESULTS: The total positive rate of Coxsackie virus B 1-6
      IgM antibody in myocarditis patients was 69.6% (135 cases), among which Cox B3
      type was as high as 40% (54 cases) of the total positive patients. The others
      were 29.6% (40 cases), 18.5% (25 cases), 7.4%(10 cases), 3.0% (4 cases), 1.5% (2
      cases) of Cox B2, Cox B4, Cox B1, Cox B5 and Cox B6 respectively. Meanwhile only
      20.4% (37 cases) Cox B IgM positive cases could be detected in 181 non
      myocarditis patients of same ages. The results showed that the positive rate of
      Cox B virus IgM antibody in clinically diagnosed myocarditis was significantly
      higher than that in control group (P <0.01). CONCLUSIONS: The Cox B viruses may
      be the main agents causing viral myocarditis in Beijing cases. Mac ELISA is an
      easy, rapid, specific and sensitive method to detect Cox B virus IgM antibody for
      early and rapid diagnosis of myocarditis.

PMID- 11471031
TI  - [Detection of viral aetiology in cerebral spinal fluid samples from 580 clinical
      cases].
AB  - OBJECTIVE: To investigate the viral aetiology in cerebral spinal fluid (Csf) from
      580 cases of CNS infection or FUO in Yuedong district from 1990 to 1997. METHODS:
      Virus isolation was done with Hep-2 and BHK-21 cells. RESULTS: 21 virus types of
      5 kinds of viruses were isolated from 113 samples (19.5%). Clinically diagnosed
      diseases included viral encephalitis 17.8% (43/242), intracranial infection 20.2%
      (47/233), paralytic diseases 24.3% (9/37), FUO 37.5% (9/24), convulsion 16.0%
      (4/25), Guillain-Barre syndrome 5.3% (1/19). Virus infection included 11 cases of
      Poliovirus (constitutional ratio 0.0973, including 1 Polio-I, 8 Polio-II, 2 Polio
      III); 54 cases of Coxsackie virus (0.477 9, including 11 CoxA24, 10 CoxBl, 2
      Cox134, 3 CoxB5); 15 cases of ECHO virus (0.1327, including 4 ECHO-24, 3 ECRO-7,
      2 ECHO-12 and each one of ECHO-3, 11,14,15,27,32); 25 cases of Enterovirus
      (0.2213, including 14 EV-70, 11 EV-71); 8 cases of Adenovirus (0.070 8, including
      3 Adv-2, 3 Adv-3 and 2 Adv7). Results of different age groups indicated there was
      significant difference (P < 0.05) in virus detection rate in two age groups.
      Virus positive rates in different years were 1990-1991 14.2% (15/106), 1992-1993
      14.1%(23/163), 1994-1995 26.1% (36/138), 1996-1997 22.5% (39/173), that showed a
      significant difference (P <0.05). CONCLUSIONS: Virus infection rate of CNS
      diseases and FUO showed an a ascending trend, and the different virus types and
      kinds were isolated in different periods.

PMID- 11471032
TI  - [Side effects after treatment with a-interferon in children with chronic viral
      hepatitis].
AB  - OBJECTIVE: This paper aimed at a long-term observation on side effects of alpha-
      IFN treatment in children with chronic viral hepatitis. METHODS: A randomized
      trial of 261 alpha-IFN treated chronic hepatitis children (183 with hepatitis B,
      78 with hepatitis C) in comparison with 114 adults was carried out to observe
      side effect of alpha-IFN treatment 5-6 years in average and 10 years the longest.
      Mean age of children was 8.7 years, with 203 males and 58 females. RESULTS: Early
      stage side effects were low to moderate fever and endemic influenza symptoms,
      which in children were more less than in adults (P < 0.001). Side effects did not
      relate to viral pathogeny (HB or HC) and pathological changes (< or = G2, > or =
      G3) in child patient. Slightly poor appetite, slight hair loss, rash and tinnitus
      would disappear gradually needed no treatment. Serum Bil, Bun, Cr, T3, T4 and TSH
      were normal in all patients. There was no long-term side effects. CONCLUSIONS:
      alpha-IFN treatment for viral hepatitis in children is safe.

PMID- 11471033
TI  - [An experimental study of a new route for Acyclovir administration for anti
      keratitis therapeutic treatment].
AB  - OBJECTIVE: To study the significance of a collagen shield made by centrifugal
      method that can deliver Acyclovir. METHODS: 28 white rabbits were divided into
      four groups for observing releasing of Acyclovir into aqueous at 0.5, 1, 3, 5
      hours after adding drugs in two different administrative ways, that were putting
      drug loaded collagen shields on one eye of the rabbit and subconjunctival
      injection of drug in another eye of the rabbit as control. The drug
      concentrations in aqueous of rabbit at different times using different
      administrative routes were measured by high-performance liquid chromatography
      (HPLC). RESULTS: At 0.5 hr of drug administration, the Acyclovir concentrations
      in aqueous of subconjunctival injected rabbits were obviously higher than that in
      collagen shields loaded rabbits (t = 4.050, P <0.01), but it became not so
      notable at the time of 1 hr. (t =2.074, P>0.05). At the time of 3 hrs and 5 hrs,
      the drug concentrations in aqueous of collagen shield loaded eyes of the rabbits
      not only were higher than that of the subconjunctival injected rabbits (t=4.761,
      t=4.190, respectively, P <0.01), but also could sustain rather a long time.
      CONCLUSIONS: A drug delivering way using collagen shield made by centrifugal
      method can replace the subconjunctival injection.

PMID- 11471034
TI  - Heparan sulfate and control of cell division: adhesion and proliferation of
      mutant CHO-745 cells lacking xylosyl transferase.
AB  - We have examined the role of cell surface glycosaminoglycans in cell division:
      adhesion and proliferation of Chinese hamster ovary (CHO) cells. We used both
      wild-type (CHO-K1) cells and a mutant (CHO-745) which is deficient in the
      synthesis of proteoglycans due to lack of activity of xylosyl transferase. Using
      different amounts of wild-type and mutant cells, little adhesion was observed in
      the presence of laminin and type I collagen. However, when fibronectin or
      vitronectin was used as substrate, there was an enhancement in the adhesion of
      wild-type and mutant cells. Only CHO-K1 cells showed a time-dependent adhesion on
      type IV collagen. These results suggest that the two cell lines present different
      adhesive profiles. Several lines of experimental evidence suggest that heparan
      sulfate proteoglycans play a role in cell adhesion as positive modulators of cell
      proliferation and as key participants in the process of cell division.
      Proliferation and cell cycle assays clearly demonstrate that a decrease in the
      amount of glycosaminoglycans does not inhibit the proliferation of mutant CHO-745
      cells when compared to the wild type CHO-K1, in agreement with the findings that
      both CHO-K1 and CHO-745 cells take 8 h to enter the S phase.

PMID- 11471035
TI  - Isolation of bovine plasma albumin by liquid chromatography and its
      polymerization for use in immunohematology.
AB  - The aim of the method described here is to remove hemoglobin, the major
      contaminant in the bovine plasma obtained from slaughterhouses, by adding a
      mixture of 19% cold ethanol and 0.6% chloroform, followed by fibrinogen and
      globulin precipitation by the Cohn method and nonspecific hemagglutinin by
      thermocoagulation. The experimental volume of bovine plasma was 2,000 ml per
      batch. Final purification was performed by liquid chromatography using the ion
      exchange gel DEAE-Sepharose FF. The bovine albumin thus obtained presented > or
      =99% purity, a yield of 25.0 +/- 1.2 g/l plasma and >71.5% recovery. N-acetyl-DL
      tryptophan (0.04 mmol/g protein) and sodium caprylate (0.04 mmol/g protein) were
      used as stabilizers and the final concentration of albumin was adjusted to 22.0%
      (w/v), pH 7.2 to 7.3. Viral inactivation was performed by pasteurization for 10 h
      at 60 degrees C. The bovine albumin for the hemagglutination tests used in
      immunohematology was submitted to chemical treatment with 0.06% (w/v)
      glutaraldehyde and 0.1% (w/v) formaldehyde at 37 degrees C for 12 h to obtain
      polymerization. A change in molecular distribution was observed after this
      treatment, with average contents of 56.0% monomers, 23.6% dimers, 12.2% trimers
      and 8.2% polymers. The tests performed demonstrated that this polymerized albumin
      enhances the agglutination of Rho(D)-positive red cells by anti-Rho(D) serum,
      permitting and improving visualization of the results.

PMID- 11471036
TI  - Alpha-smooth muscle actin and proliferating cell nuclear antigen expression in
      focal segmental glomerulosclerosis: functional and structural parameters of renal
      disease progression.
AB  - The aim of the present study was to investigate the expression of alpha-smooth
      muscle actin (alpha-SM-actin) and proliferating cell nuclear antigen (PCNA) in
      renal cortex from patients with focal segmental glomerulosclerosis (FSGS) and
      their correlations with parameters of renal disease progression. We analyzed
      renal biopsies from 41 patients with idiopathic FSGS and from 14 control
      individuals. The alpha-SM-actin immunoreaction was evaluated using a score that
      reflected the changes in the extent and intensity of staining in the glomerular
      or cortical area. The PCNA reaction was quantified by counting the labeled cells
      of the glomeruli or renal cortex. The results, reported as median +/- percentile
      (25th; 75th), showed that the alpha-SM-actin scores in the glomeruli and
      tubulointerstitium from the renal cortex were 2.0 (2.0; 4.0) and 3.0 (3.0; 4.0),
      respectively, in patients with FSGS, and 0.5 (0.0; 1.0) and 0.0 (0.0; 0.5) in the
      controls. The number of PCNA-positive cells per glomerulus and graded field of
      tubulointerstitium from the renal cortex was 0.2 (0.0; 0.4) and 1.1 (0.3; 2.2),
      respectively, for patients with FSGS, and 0.0 (0.0; 0.5) and 0.0 (0.0; 0.0) for
      controls. The present data showed an increase of alpha-SM-actin and PCNA
      expression in glomeruli and renal cortex from FSGS patients. The extent of
      immunoreaction for alpha-SM-actin in the tubulointerstitial area was correlated
      with the intensity of proteinuria. However, there was no correlation between the
      kidney expression of these proteins and the reciprocal of plasma creatinine level
      or renal fibrosis. These findings suggest that the immunohistochemical
      alterations may be reversible.

PMID- 11471037
TI  - Diagnostic investigation of ventilator-associated pneumonia using bronchoalveolar
      lavage: comparative study with a postmortem lung biopsy.
AB  - The purpose of the present study was to validate the quantitative culture and
      cellularity of bronchoalveolar lavage (BAL) for the diagnosis of ventilator
      associated pneumonia (VAP). A prospective validation test trial was carried out
      between 1992 and 1997 in a general adult intensive care unit of a teaching
      hospital. Thirty-seven patients on mechanical ventilation with suspected VAP who
      died at most three days after a BAL diagnostic procedure were submitted to a
      postmortem lung biopsy. BAL effluent was submitted to Gram staining, quantitative
      culture and cellularity count. Postmortem lung tissue quantitative culture and
      histopathological findings were considered to be the gold standard exams for VAP
      diagnosis. According to these criteria, 20 patients (54%) were diagnosed as
      having VAP and 17 (46%) as not having the condition. Quantitative culture of BAL
      effluent showed 90% sensitivity (18/20), 94.1% specificity (16/17), 94.7%
      positive predictive value and 88.8% negative predictive value. Fever and
      leukocytosis were useless for VAP diagnosis. Gram staining of BAL effluent was
      negative in 94.1% of the patients without VAP (16/17). Regarding the total
      cellularity of BAL, a cut-off point of 400,000 cells/ml showed a specificity of
      94.1% (16/17), and a cut-off point of 50% of BAL neutrophils showed a sensitivity
      of 90% (19/20). In conclusion, BAL quantitative culture, Gram staining and
      cellularity might be useful in the diagnostic investigation of VAP.

PMID- 11471038
TI  - Cytogenetic description of breast fibroadenomas: alterations related solely to
      proliferation?
AB  - Twelve breast fibroadenomas were analyzed cytogenetically and only four were
      found to have clonal alterations. The presence of chromosomal alterations in
      fibroadenomas must be the consequence of the proliferating process and must not
      be related to the etiology of this type of lesion. In contrast, the few
      fibroadenomas that exhibit chromosomal alterations are likely to be those
      presenting a risk of neoplastic transformation. Clonal numerical alterations
      involved chromosomes 8, 18, 19, and 21. Of the chromosomal alterations found in
      the present study, only monosomy of chromosomes 19 and 21 has been reported in
      breast fibroadenomas. The loss of chromosome 21 was the most frequent alteration
      found in our sample. The study of benign proliferations and their comparison with
      chromosome alterations in their malignant counterparts ought to result in a
      better understanding of the genes acting on cell proliferation alone, and of the
      genes that cause these cells to exhibit varied behaviors such as recurrences,
      spontaneous regression and fast growth.

PMID- 11471039
TI  - Intercellular contact-dependent survival of human A549, NCI-H596 and NCI-H520 non
      small cell lung carcinoma cell lines.
AB  - In the present study, we examined the relationship between cell phenotype and
      cell survival of three human non-small cell lung carcinoma cell lines (A549, NCI
      H596 and NCI-H520). Cells in exponential growth at various densities were
      incubated for 24 h at 37 degrees C in a 5% CO2 humidified atmosphere and then
      exposed to UV radiation for 1 min (256 nm, 40 W, source-to-target distance 100
      cm). After two days the surviving cells were quantified by sulforhodamine beta
      staining and DNA fragmentation assay. The differences in UV sensitivity at 60 x
      10(3) cells/cm2 among the cell lines were not related to the proliferative state
      of the cells but to the extent of intercellular contact. In contrast to A549 and
      NCI-H596, irradiated NCI-H520 cells presented lower DNA fragmentation and an
      aggregated cell culture phenotype even prior to confluence, suggesting that a
      contact-effect mechanism provides further protection against UV radiation.

PMID- 11471040
TI  - Effect of 17beta-estradiol or alendronate on the bone densitometry, bone
      histomorphometry and bone metabolism of ovariectomized rats.
AB  - The objective of the present study was to evaluate the effect of 17beta-estradiol
      or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats.
      One group underwent sham ovariectomy (control, N = 10), and the remaining three
      underwent double ovariectomy. One ovariectomized group did not receive any
      treatment (OVX, N = 12). A second received subcutaneous 17beta-estradiol at a
      dose of 30 microg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous
      alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry,
      densitometry, osteocalcin and deoxypyridinoline measurements were applied to all
      groups. After 6 weeks there was a significant decrease in bone mineral density
      (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and
      17beta-estradiol increased the BMD of ovariectomized rats, with the BMD of the
      OVX-A group being higher than that of the OVX-E group. Histomorphometry of the
      distal femur showed a decrease in trabecular volume in the untreated group (OVX),
      and an increase in the two treated groups, principally in the alendronate group.
      In OVX-A there was a greater increase in trabecular number. An increase in
      trabecular thickness, however, was seen only in the OVX-E group. There was also a
      decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and
      deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A.
      Although both drugs were effective in inhibiting bone loss, alendronate proved to
      be more effective than estradiol at the doses used in increasing bone mass.

PMID- 11471041
TI  - Lack of evidence for superantigen activity of Toxoplasma gondii towards human T
      cells.
AB  - Toxoplasma gondii is an obligatory intracellular parasite whose life cycle may
      include man as an intermediate host. More than 500 million people are infected
      with this parasite worldwide. It has been previously reported that T. gondii
      contains a superantigen activity. The purpose of the present study was to
      determine if the putative superantigen activity of T. gondii would manifest
      towards human T cells. Peripheral blood mononuclear cells (PBMC) from individuals
      with no previous contact with the parasite were evaluated for proliferation as
      well as specific Vbeta expansion after exposure to Toxoplasma antigens. Likewise,
      PBMC from individuals with the congenital infection were evaluated for putative
      Vbeta family deletions in their T cell repertoire. We also evaluated, over a
      period of one year, the PBMC proliferation pattern in response to Toxoplasma
      antigens in patients with recently acquired infection. Some degree of
      proliferation in response to T. gondii was observed in the PBMC from individuals
      never exposed to the parasite, accompanied by specific Vbeta expansion,
      suggesting a superantigen effect. However, we found no specific deletion of Vbeta
      (or Valpha) families in the blood of congenitally infected individuals.
      Furthermore, PBMC from recently infected individuals followed up over a period of
      one year did not present a reduction of the Vbeta families that were originally
      expanded in response to the parasite antigens. Taken together, our data suggest
      that T. gondii does not have a strong superantigen activity on human T cells.

PMID- 11471042
TI  - Production and characterization of a monoclonal antibody against an Ascaris suum
      allergenic component.
AB  - Ascaris suum allergenic components (PIII) separated by gel filtration
      chromatography of an adult worm extract were used to immunize BALB/c mice.
      Popliteal lymph node cells taken from the immunized animals were fused with SP2/O
      myeloma cells using polyethylene glycol (MW 1450) as fusogen. The hybridomas were
      cultured in HAT-containing medium and cloned at limiting dilutions. Supernatants
      from the growing hybrids were screened by ELISA using plates coated with PIII or
      the A. suum crude extract. The monoclonal antibody obtained, named MAC-3 (mouse
      anti-A. suum allergenic component), is an IgG1 kappa mouse immunoglobulin that
      specifically recognizes a 29,000 molecular weight protein (called allergenic
      protein) with an affinity constant of 1.7 x 10(9) M-1. The A. suum components
      recognized by MAC-3 induce specific IgE antibody production in immunized BALB/c
      mice. Ascitic fluid induced in Swiss mice by injecting ip the hybridoma cells and
      incomplete Freund's adjuvant was purified by affinity chromatography using a
      protein A-Sepharose column. The purified monoclonal antibody was then coupled to
      activated Sepharose beads in order to isolate the A. suum allergenic component
      from the whole extract by affinity chromatography.

PMID- 11471043
TI  - Pupil size following dark adaptation in patients with retinitis pigmentosa.
AB  - According to the equivalent light hypothesis, molecular defects in the
      photoreceptor lead to a continuous activation of the photoreceptor cascade in a
      manner equivalent to real light. The consequences in diseases such as retinitis
      pigmentosa (RP) are as disruptive to the cells as real light. Two forms of the
      equivalent light hypothesis can be distinguished: strong - mutations in rhodopsin
      or other cascade proteins in some forms of RP continuously excite the visual
      phototransduction cascade; weak - disruption of outer segments in all patients
      with RP eliminates circulating dark current and blocks neurotransmitter release
      in a manner similar to real light. Both forms of the equivalent light hypothesis
      predict that pupils of patients with RP will be constricted like those of normal
      subjects in the light. The purpose of this study was to test the equivalent light
      hypothesis by determining whether steady-state pupil diameter following full dark
      adaptation is abnormally small in any of a sample of patients with RP. Thirty
      five patients with RP and 15 normal subjects were tested. Direct steady-state
      pupillometric measures were obtained from one eye in a full-field dome after 45
      min of dark adaptation by videotaping the pupil with an infrared camera. Mean
      pupil diameter in the dark was comparable (t = -0.15, P = 0.88) between patients
      with RP (6.85 +/- 0.58 mm) and normal subjects (6.82 +/- 0.76 mm). The results of
      the present study are clearly counter to the prediction of the second (weaker)
      form of the equivalent light hypothesis.

PMID- 11471044
TI  - Environmental blue light prevents stress in the fish Nile tilapia.
AB  - The present study aimed to test the effects of blue, green or white light on the
      stress response of the Nile tilapia, Oreochromis niloticus (L.). Each color was
      tested on two groups of isolated adult Nile tilapia (8 replicates each): one
      being subjected to confinement stress, and the other not (control). A different
      environmental color was imposed on each compartment by covering the light source
      with cellophane of the respective color (green or blue; no cellophane was used
      for white light). The intensity of green, white and blue lights was 250, 590 and
      250 lux, respectively. Basal plasma cortisol levels were determined for each fish
      prior to the experimental procedures. The fish were confined by being displaced
      toward one side of the aquarium using an opaque partition for 1 h both in the
      morning and the afternoon of the two consecutive days of the test. At the end of
      this 48-h period, plasma cortisol levels were measured again. Basal cortisol
      levels (ng/ml) were similar for each group (ANOVA, F(2;42) = 0.77, P = 0.47).
      Thus, plasma cortisol levels were analyzed in terms of variation from their
      respective basal level. After confinement, plasma cortisol levels were not
      increased in fish submitted to a blue light environment. Thus, blue light
      prevents the confinement-induced cortisol response, an effect not necessarily
      related to light intensity.

PMID- 11471045
TI  - A time-dependent, two-step binding mode of the nitro dye flavianic acid to
      trypsin in acid media.
AB  - Synthetic dyes bind to proteins causing selective coprecipitation of the
      complexes in acid aqueous solution by a process of reversible denaturation that
      can be used as an alternative method for protein fractionation. The events that
      occur before precipitation were investigated by equilibrium dialysis using bovine
      trypsin and flavianic acid as a model able to cause coprecipitation. A two-step
      mode of interaction was found to be dependent on the incubation periods allowed
      for binding, with pronounced binding occurring after 42 h of incubation. The
      first step seems to involve hydration effects and conformational changes induced
      by binding of the first dye molecule, following rapid denaturation due to the
      binding of six additional flavianate anions to the macromolecule.

PMID- 11471046
TI  - Influence of exercise on the activity and the distribution between free and bound
      forms of glycolytic and associated enzymes in tissues of horse mackerel.
AB  - The effects of short-term burst (5 min at 1.8 m/s) swimming and long-term cruiser
      (60 min at 1.2 m/s) swimming on maximal enzyme activities and enzyme distribution
      between free and bound states were assessed for nine glycolytic and associated
      enzymes in tissues of horse mackerel, Trachurus mediterraneus ponticus. The
      effects of exercise were greatest in white muscle. The activities of
      phosphofructokinase (PFK), pyruvate kinase (PK), fructose-1,6-bisphosphatase
      (FBPase), and phosphoglucomutase (PGM) all decreased to 47, 37, 37 and 67%,
      respectively, during 60-min exercise and all enzymes except phosphoglucoisomerase
      (PGI) and PGM showed a change in the extent of binding to subcellular particulate
      fractions during exercise. In red muscle, exercise affected the activities of
      PGI, FBPase, PFK, and lactate dehydrogenase (LDH) and altered percent binding of
      only PK and LDH. In liver, exercise increased the PK activity 2.3-fold and
      reduced PGI 1.7-fold only after 5 min of exercise but altered the percent binding
      of seven enzymes. Fewer effects were seen in brain, with changes in the
      activities of aldolase and PGM and in percent binding of hexokinase, PFK and PK.
      Changes in enzyme activities and in binding interactions with subcellular
      particulate matter appear to support the altered demands of tissue energy
      metabolism during exercise.

PMID- 11471047
TI  - Effects of small doses of ouabain on the arterial blood pressure of anesthetized
      hypertensive and normotensive rats.
AB  - Ouabain increases vascular resistance and may induce hypertension by inhibiting
      the Na+ pump. The effects of 0.18 and 18 microg/kg, and 1.8 mg/kg ouabain
      pretreatment on the phenylephrine (PHE; 0.1, 0.25 and 0.5 microg, in bolus)
      evoked pressor responses were investigated using anesthetized normotensive
      (control and uninephrectomized) and hypertensive (1K1C and DOCA-salt treated)
      rats. Treatment with 18 microg/kg ouabain increased systolic and diastolic blood
      pressure in all groups studied. However, the magnitude of this increase was
      larger for the hypertensive 1K1C and DOCA-salt rats than for normotensive
      animals, while the pressor effect of 0.18 microg/kg ouabain was greater only in
      DOCA-salt rats. A very large dose (1.8 mg/kg) produced toxic effects on the
      normotensive control but not on uninephrectomized or 1K1C rats. Rat tail vascular
      beds were perfused to analyze the effects of 10 nM ouabain on the pressor
      response to PHE. In all animals, 10 nM ouabain increased the PHE pressor
      response, but this increase was larger in hypertensive DOCA-salt rats than in
      normotensive and 1K1C rats. Results suggested that a) increases in diastolic
      blood pressure induced by 18 microg/kg ouabain were larger in hypertensive than
      normotensive rats; b) in DOCA-salt rats, smaller ouabain doses had a stronger
      effect than in other groups; c) hypertensive and uninephrectomized rats were less
      sensitive to toxic doses of ouabain, and d) after treatment with 10 nM ouabain
      isolated tail vascular beds from DOCA-salt rats were more sensitive to the
      pressor effect of PHE than those from normotensive and 1K1C hypertensive rats.
      These data suggest that very small doses of ouabain, which might produce
      nanomolar plasma concentrations, enhance pressor reactivity in DOCA-salt
      hypertensive rats, supporting the idea that endogenous ouabain may contribute to
      the increase and maintenance of vascular tone in hypertension.

PMID- 11471048
TI  - Regulation of the renal proximal tubule second sodium pump by angiotensins.
AB  - For several years it was believed that angiotensin II (Ang II) alone mediated the
      effects of the renin-angiotensin system. However, it has been observed that other
      peptides of this system, such as angiotensin-(1-7) (Ang-(1-7)), present
      biological activity. The effect of Ang II and Ang-(1-7) on renal sodium excretion
      has been associated, at least in part, with modulation of proximal tubule sodium
      reabsorption. In the present review, we discuss the evidence for the involvement
      of Na+-ATPase, called the second sodium pump, as a target for the actions of
      these compounds in the regulation of proximal tubule sodium reabsorption.

PMID- 11471049
TI  - Trans-NIH neuroscience initiatives on mouse phenotyping and mutagenesis.
AB  - In the post-genomic era, the laboratory mouse will excel as a premier mammalian
      system to study normal and disordered biological processes, in part because of
      low cost, but largely because of the rich opportunities that exist for exploiting
      genetic tools and technologies in the mouse to systematically determine mammalian
      gene function. Many robust models of human disease may therefore be developed,
      and these in turn will provide critical clues to understanding gene function. The
      full potential of the mouse for understanding many of the neural and behavioral
      phenotypes of relevance to neuroscientists has yet to be realized. With the full
      anatomy of the mouse genome at hand, researchers for the first time will be able
      to move beyond traditional gene-by-gene approaches and take a global view of gene
      expression patterns crucial for neurobiological processes. In response to an
      action plan for mouse genomics developed on the basis of recommendations from the
      scientific community, seven institutes of the National Institutes of Health (NIH)
      initiated in 1999 a mouse genetics research program that specifically focused on
      neurobiology and complex behavior. The specific goals of these neuroscience
      initiatives are to develop high-throughput phenotyping assays and to initiate
      genome-wide mutagenesis projects to identify hundreds of mutant strains with
      heritable abnormalities of high relevance to neuroscientists. Assays and mutants
      generated in these efforts will be made widely available to the scientific
      community, and such resources will provide neuroscientists unprecedented
      opportunities to elucidate the molecular mechanisms of neural function and
      complex behavior. Such research tools ultimately will permit the manipulation and
      analysis of the mouse genome, as a means of gaining insight into the genetic
      bases of the mammalian nervous system and its complex disorders.

PMID- 11471050
TI  - Genomic structure, functional comparison, and tissue distribution of mouse Cd59a
      and Cd59b.
AB  - CD59 is a crucial complement regulatory protein that inhibits the terminal step
      of the complement activation cascade by interfering with the binding of C9 to C5b
      8, thus preventing the formation of the membrane attack complex (MAC). We
      recently reported that the mouse genome contains two Cd59 genes, while the human
      and rat genomes each contain only one Cd59 gene (Qian et al. 2000). Here, we
      describe the genomic structure, comparative activity, and tissue distribution of
      these two mouse genes, designated Cd59a and Cd59b. The mouse Cd59 genes encompass
      a total of 45.6 kb with each gene having four exons. Cd59a spans 19 kb, and Cd59b
      spans 15 kb, with approximately 11.6 kb of genomic DNA separating the two genes.
      The overall sequence similarity between Cd59a and Cd59b is approximately 60%. The
      sequence similarity between exon 2, exon 3, and exon 4 and the respective
      flanking regions between the two genes is over 85%, but exon 1 and its flanking
      regions are totally different. Comparative studies of the activity of both genes
      as inhibitors of MAC formation revealed that Cd59b has a specific activity that
      is six times higher than that of Cd59a. Using polyclonal antibodies specific to
      either Cd59a or Cd59b, we showed that Cd59a and Cd59b are both widely expressed
      in the kidneys, brain, lungs, spleen, and testis, as well as in the blood vessels
      of most mouse tissues. Interestingly, testicular Cd59a appeared to be expressed
      exclusively in spermatids, whereas Cd59b was expressed in more mature sperm
      cells. These results suggest that even though Cd59a and Cd59b are expressed in
      multiple tissues, they may play some different roles, particularly in
      reproduction.

PMID- 11471051
TI  - Source and component genes of a 6-200 Mb gene cluster in the house mouse.
AB  - We identified and analyzed the genes Sp100, Csprs, and Ifi75 in two members of
      the genus Mus, M. musculus and M. caroli. Sp100 is a nuclear dot gene; Csprs and
      Ifi75 are novel genes encoding a putative G-protein coupled receptor (GPCR) and a
      putative transcriptional coactivator, respectively. A fourth gene, Sp100-rs,
      occurs in M. musculus, but not in M. caroli. Sp100-rs is a chimeric gene which
      arose by fusion of Sp100 and Csprs copies. Sp100-rs and Ifi75 are components of a
      repeat cluster that extends over 6-200 Mb of the M. musculus genome. The Sp100-rs
      fusion gene arose only 1-2 million years ago and has become fixed and amplified
      in M. musculus. Although the gene is transcribed, it appears to have no function.
      The repeat cluster may have become fixed in the species as a 'hitchhiker' in a
      'selective sweep'.

PMID- 11471052
TI  - Identification and expression of a mouse ortholog of A2BP1.
AB  - Human ataxin-2 contains a polyglutamine repeat that is expanded in patients with
      spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is highly conserved in evolution
      with orthologs in mouse, Caenorhabditis elegans, and Drosophila melanogaster. It
      interacts at its C-terminus with ataxin-2 binding protein 1, A2BP1. This study
      presents a highly conserved mouse ortholog of A2BP1, designated A2bp1. The amino
      acid sequence of the human and mouse protein is 97.6% identical. This remarkable
      degree of conservation supports the fact that these proteins have an important
      basic function in development and differentiation. Sequence analysis reveals the
      existence of RNA binding motifs. The A2bp1 transcript was found in various
      regions of the CNS including cerebellum, cerebral cortex, brain stem, and
      thalamus/hypothalamus. The A2bp1 protein was detected by immunocytochemistry in
      the CNS and connective tissue of the mouse embryo starting at stage E11, as well
      as in the heart at all stages. Mouse embryos showed varying expression of A2bp1
      at all stages. Previous studies in other model systems had implicated the
      orthologs of ataxin-2 and A2BP1 in development. This study suggests a role for
      A2bp1 in embryogenesis as well as in the adult nervous system, possibly mediated
      by a function in RNA distribution or processing.

PMID- 11471053
TI  - Mouse Tdho abnormality results from double point mutations of the emopamil
      binding protein gene (Ebp).
AB  - Mouse Tdho (Tattered-Hokkaido) was described as being allelic with Td in our
      previous study. Both allelic genes, which are located at the same position on the
      centromere of the X Chromosome (Chr), generate similar phenotypes such as male
      embryonic lethality, and in heterozygous females, hyperkeratotic skin, skeletal
      abnormalities, and growth retardation. The emopamil binding protein gene (Ebp)
      emerged as a candidate for mouse Tdho mutation, since the Td gene was recently
      determined to result from a point mutation of Ebp. In this study, Ebp cDNA of
      Tdho was demonstrated to possess double point mutations that cause two amino acid
      changes from Leu to Pro at position 132 and from Ser to Cys at 133 in EBP
      protein. EBP participates in cholesterol biosynthesis, and cholest-8(9)-en-3beta
      ol was found to be increased in the plasma of Tdho adult females but not in that
      of normal mice. From these results, a loss of function was expected for the EBP
      protein encoded by Tdho. Both the phenotypes and genes responsible for Tdho as
      well as Td are quite similar to those of human X-linked chondrodysplasia punctata
      (CDPX2).

PMID- 11471054
TI  - The ROSA26 LacZ-neo(R) insertion confers resistance to mammary tumors in
      Apc(Min/+) mice.
AB  - B6.129S7-Gtrosa26 (ROSA26) mice carry a LacZ-neo(R) insertion on Chromosome (Chr)
      6, made by promoter trapping with AB1 129 ES cells. Female C57BL/6J Apc(Min/+)
      (B6 Min/+) mice are very susceptible to the induction of mammary tumors after
      treatment with ethylnitrosourea (ENU). However, ENU-treated B6 mice carrying both
      Apc(Min) and ROSA26 are resistant to mammary tumor formation. Thus, ROSA26 mice
      carry a modifier of Min-induced mammary tumor susceptibility. We have previously
      mapped the modifier to a 4-cM interval of 129-derived DNA that also contains the
      ROSA26 insertion. Here we report additional evidence for the effect of the ROSA26
      insertion on mammary tumor formation. To test the hypothesis that the resistance
      was due to a linked modifier locus, we utilized two approaches. We have derived
      and tested two lines of mice that are congenic for 129-derived DNA within the
      minimal modifier interval and show that they are as susceptible to mammary tumors
      as are B6 mice. Additionally, we analyzed a backcross population segregating for
      the insertion and show that mice carrying the insertion are more resistant to
      mammary tumor development than are mice not carrying the insertion. Thus, the
      resistance is not due to a 129-derived modifier allele, but must be due to the
      ROSA26 insertion. In addition, the effect of the ROSA26 insertion can be detected
      in a backcross population segregating for other mammary modifiers.

PMID- 11471055
TI  - Utilization of marker-assisted congenics to map two blood pressure quantitative
      trait loci in Dahl rats.
AB  - A broad Chromosome (Chr) 10 region of the Dahl salt-sensitive (S) rat was shown
      by linkage and the use of congenic strains to contain a blood pressure (BP)
      quantitative trait locus (QTL). To further narrow down the region harboring the
      QTL, four congenic strains carrying smaller segments were made by replacing
      various segments of the S rats with the homologous segments of the Lewis (LEW)
      rats. The construction of these congenic strains was facilitated by a genome-wide
      marker screening. One congenic strain, assigned as S.L4, showed a BP-lowering
      effect, and the region harboring a BP QTL, designated QTL1, is localized to a
      segment of about 15 cM. Two other strains, assigned as S.L2 and S.L5, contained
      an overlapping segment, and both showed a BP-lowering effect. In contrast, the
      fourth congenic strain, assigned as S.L1, contained a smaller and shared fragment
      with S.L2 and S.L5, but it did not have a BP-lowering effect. Deducing from the
      segment in common in S.L2 and S.L5, and not shared between S.L1 and both congenic
      strains S.L2 and S.L5, the region harboring a QTL, designated as QTL2, was
      narrowed to about 12 cM. The current work showed the general applicability of the
      'speed congenic' approach to map and fine-map BP QTL.

PMID- 11471056
TI  - ATP6H, a subunit of vacuolar ATPase involved in metal transport: evaluation in
      canine copper toxicosis.
AB  - Copper toxicosis (CT), resulting in liver disease, occurs commonly in Bedlington
      terriers. Canine CT is of particular interest because identification of the
      causative gene may lead to the discovery of another important gene in the copper
      transport pathway possibly related to human copper diseases not yet identified.
      Homologs of the copper transporting ATPase ATP7B, defective in Wilson disease,
      and the copper chaperone ATOX1 were potential candidates, but both have been
      excluded. The CT locus in Bedlington terriers has been mapped to canine
      chromosome region CFA10q26, which has a syntenic human chromosome region, HAS2p13
      21. The gene ATP6H, for human vacuolar proton-ATPase subunit M9.2, is associated
      with copper and iron transport in yeast and has been mapped to HAS2p21 and
      suggested as a candidate gene for CT. We cloned canine ATP6H, which encodes a
      predicted protein with 99% amino acid sequence identity to the orthologous human
      protein. Canine ATP6H shows a conserved potential metal binding site, CSVCC, and
      a glycosylation site, NET. The canine ATP6H is organized into four exons, with a
      246-bp open reading frame. Sequence analysis of the coding regions showed no
      mutations in ATP6H from genomic DNA of an affected dog. We have also identified
      two, apparently non-transcribed canine ATP6H pseudogenes. Mapping of the true
      ATP6H gene and a marker closely linked to the CT locus on a canine radiation
      hybrid panel indicted lack of close physical association. We have therefore
      excluded canine ATP6H as a candidate gene for canine copper toxicosis, indicating
      that some other unidentified gene is responsible for this copper storage disease.

PMID- 11471057
TI  - Canine TCOF1; cloning, chromosome assignment and genetic analysis in dogs with
      different head types.
AB  - We describe the construction of a dog embryonic head/neck cDNA library and the
      isolation of the dog homolog of the Treacher Collins Syndrome gene, TCOF1. The
      protein shows a similar three-domain structure to that described for human TCOF1,
      but the dog gene lacks exon 10 and contains two exons not present in the human
      sequence. In addition, exon 19 is differentially spliced in the dog. How these
      structural differences relate to TCOF1 phosphorylation is discussed. Isolation of
      a genomic clone allowed the exon/intron boundaries to be characterized and the
      dog TCOF1 gene to be mapped to CF Chr 4q31, a region syntenic to human Chr 5.
      Genetic analysis of DNA of dogs from 13 different breeds identified nine DNA
      sequence variants, three of which gave rise to amino acid substitutions. Grouping
      dogs according to head type showed that a C396T variant, leading to a Pro117Ser
      substitution, is associated with skull/face shape in our dog panel. The numbers
      are small, but the association between the T allele and brachycephaly, broad
      skull/short face, was highly significant (p = 0.000024). The short period of time
      during which the domestic dog breeds have been established suggests that this
      mutation has arisen only once in the history of dog domestication.

PMID- 11471058
TI  - A molecular genome scan analysis to identify chromosomal regions influencing
      economic traits in the pig. I. Growth and body composition.
AB  - Genome scans can be employed to identify chromosomal regions and eventually genes
      (quantitative trait loci or QTL) that control quantitative traits of economic
      importance. A three-generation resource family was developed by using two
      Berkshire grand sires and nine Yorkshire grand dams to detect QTL for growth and
      body composition traits in pigs. A total of 525 F2 progeny were produced from 65
      matings. All F2 animals were phenotyped for birth weight, 16-day weight, growth
      rate, carcass weight, carcass length, back fat thickness, and loin eye area.
      Animals were genotyped for 125 microsatellite markers covering the genome. Least
      squares regression interval mapping was used for QTL detection. All carcass
      traits were adjusted for live weight at slaughter. A total of 16 significant QTL,
      as determined by a permutation test, were detected at the 5% chromosome-wise
      level for growth traits on Chromosomes (Chrs) 1, 2, 3, 4, 6, 7, 8, 9, 11, 13, 14,
      and X, of which two were significant at the 5% genome-wise level and two at the
      1% genome-wise level (on Chrs 1, 2, and 4). For composition traits, 20 QTL were
      significant at the 5% chromosome-wise level (on Chrs 1, 4, 5, 6, 7, 12, 13, 14,
      18), of which one was significant at the 5% genome-wise level and three were
      significant at the 1% genome-wise level (on Chrs 1, 5, and 7). For several QTL
      the favorable allele originated from the breed with the lower trait mean.

PMID- 11471059
TI  - A molecular genome scan analysis to identify chromosomal regions influencing
      economic traits in the pig. II. Meat and muscle composition.
AB  - Molecular genetic markers can be used to identify chromosomal regions that
      contain quantitative trait loci (QTL) that control meat quality and muscle
      composition traits in farm animals. To study this in pigs, a resource family was
      generated from a cross between two Berkshire grand sires and nine Yorkshire grand
      dams. A total of 525 F2 progeny from 65 matings of F1 parents were produced.
      Phenotypic data on 28 meat quality traits (drip loss, water holding capacity,
      firmness, color, marbling, percentage cholesterol, ultimate pH, fiber type, and
      several sensory panel and cooking traits) were collected on the F2 animals.
      Animals were genotyped for 125 microsatellite markers covering the entire genome.
      Least squares regression interval mapping was used for QTL detection.
      Significance thresholds were determined by permutation tests. A total of 60 QTL
      were detected at the 5% chromosome level for meat quality traits, on Chrs 1, 2,
      4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 17, 18, and X, of which 9 and 1 QTL were
      significant at the 5% and 1% genome-wise levels (on Chrs 1, 5, 12, 15, and 17),
      respectively.

PMID- 11471060
TI  - A mammary gland EST showing linkage disequilibrium to a milk production QTL on
      bovine Chromosome 14.
AB  - As part of a genome scan, ESTs derived from mammary gland tissue of a lactating
      cow were used as candidate genes for quantitative trait loci (QTL), affecting
      milk production traits. Resource families were genotyped with 247 microsatellite
      markers and 4 polymorphic ESTs. It was shown by linkage analysis that one of
      these ESTs, KIEL_E8, mapped to the centromeric region of bovine Chromosome (Chr)
      14. Regression analysis revealed the presence of a QTL, with significant effect
      on milk production, in this chromosome region, and analysis of variance showed no
      significant interaction of marker genotype and family. The estimated significant
      differences between homozygous marker genotypes were 140 kg milk, -5.02 kg fat
      yield, and 2.58 kg protein yield for the first 100 days of lactation. Thus, there
      was strong evidence for a complete or nearly complete linkage disequilibrium
      between KIEL_E8 and the QTL. To identify the biological function of KIEL_E8, we
      extended the sequence for 869 bp by 5'-RACE. A 560-bp fragment of this shows a
      90.9% similarity to a gene encoding a cysteine- and histidine-rich cytoplasmic
      protein in mouse. Although such a protein may have a regulatory function for
      lactation and a linkage disequilibrium between the EST marker and the QTL has
      been observed, it remains to be elucidated whether they are identical or not.
      Nevertheless, KIEL_E8 will be an efficient marker to perform marker-assisted
      selection in the Holstein-Friesian population.

PMID- 11471061
TI  - Inbred strain variation in contextual and cued fear conditioning behavior.
AB  - A number of commonly used inbred strains were surveyed in a fear-conditioning
      paradigm conducted with an automated computer-controlled system. Control studies
      were used to verify the automated system. Response to shock was also monitored to
      determine if it was associated with contextual and/or cued conditioning behavior.
      After three pairings of tone with shock, fear conditioning was measured 24 h
      later in 129S1/SvImJ (129), A/J (A), BALB/cByJ (BALB), C3H/HeJ (C3H), C57BL/6J
      (B6), CBA/J (CBA), DBA/2J (D2), and FVB/NJ (FVB) male and female mice. There were
      both significant strain and sex differences in response. To determine the effects
      of vision on this behavior, C3H mice (with retinal degeneration) were compared
      with C3.BLiA-+Pde6b congenics (without retinal degeneration). Here, vision was
      found to play a minimal role in responsiveness in this paradigm. Because this
      fear-conditioning test is automated, it can be used for the rapid screening of a
      large number of mice, such as required for mutagenesis studies.

PMID- 11471062
TI  - High-throughput sequence identification of gene coding variants within alcohol
      related QTLs.
AB  - Low initial response to alcohol has been shown to be among the best predictors of
      development of alcoholism. A similar phenotypic measure, difference in initial
      sensitivity to ethanol, has been used for the genetic selection of two mouse
      strains, the Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice, and for
      the subsequent identification of four quantitative trait loci (QTLs) for alcohol
      sensitivity. We now report the application of high throughput comparative gene
      sequencing in the search for genes underlying these four QTLs. To carry out this
      search, over 1.7 million bases of comparative DNA sequence were generated from 68
      candidate genes within the QTL intervals, corresponding to a survey of over
      36,000 amino acids. Eight central nervous system genes, located within these
      QTLs, were identified that contain a total of 36 changes in protein coding
      sequence. Some of these coding variants are likely to contribute to the
      phenotypic variation between ILS/ISS animals, including sensitivity to alcohol,
      providing specific new genetic targets potentially important to the neuronal
      actions of alcohol.

PMID- 11471063
TI  - The mouse Supt16h/Fact140 gene, encoding part of the FACT chromatin transcription
      complex, maps close to Tcra and is highly expressed in thymus.

PMID- 11471064
TI  - Experimental and computational approaches yield a high-resolution, 1-Mb physical
      map of the region harboring the mouse t haplotype sterility factor, tcs1.

PMID- 11471065
TI  - Biomechatronics--assisting the impaired motor system.
AB  - Biomechatronics concerns the interdisciplinary field of interaction with the
      human neuromuscular-skeletal system with the objective to assist impaired human
      motor control. In this field technology is developed that integrates
      neuroscience, robotics, interface and sensor technology, dynamic systems and
      control theory. The primary issue in this field concerns the concepts of
      assisting impaired human motor function. The secondary, derived, issue concerns
      possible methods of interfacing with the human body at all hierarchical levels of
      the human motor system. The application of motor assist systems may serve several
      goals: it can take over part of the affected motor control, enable the
      physiological motor system to perform the desired function or aid in training the
      impaired physiological system. The progress in these issues are reviewed and
      their potential implications for assistance of the impaired human motor system
      are discussed.

PMID- 11471066
TI  - Direct, autocrine and paracrine effects of cyclic stretch on growth of myocytes
      and fibroblasts isolated from neonatal rat ventricles.
AB  - Several studies have demonstrated that static stretch of cardiomyocytes induces
      cardiomyocyte hypertrophy. We investigated the effects of cyclic stretch, a more
      physiological stimulus, on protein synthesis and DNA synthesis of rat ventricular
      cardiomyocytes and cardiofibroblasts. Further-more, we investigated whether these
      effects are caused by autocrine mechanisms. In addition, we studied the paracrine
      influences of stretched cardiofibroblasts on cardiomyocyte growth. Short-term
      cyclic stretch (0-24 h) of cardiomyocytes induced a growth response indicative of
      cardiomyocyte hypertrophy, given the fact that increased rates of protein
      synthesis and DNA synthesis were accompanied by an elevated release of atrial
      natriuretic peptide into the culture medium. In cardiofibroblasts, short-term
      cyclic stretch also induced a growth response as indicated by an increased rate
      of protein synthesis and DNA synthesis. Furthermore, incubation of stationary
      cardiofibroblasts with conditioned medium derived from stretched
      cardiofibroblasts revealed an autocrine effect of stretch as illustrated by an
      increased rate of protein synthesis in stationary cardiofibroblasts. In analogy,
      there was an autocrine effect of stretch on stationary cardiomyocytes incubated
      with conditioned medium derived from stretched cardiomyocytes. Moreover, we
      observed a paracrine effect of the conditioned medium derived from stretched
      cardiofibroblasts on stationary cardiomyocytes. Thus, short-term cyclic stretch
      of cardiomyocytes and cardiofibroblasts induces growth responses that are the
      result of direct, autocrine, and paracrine effects. These autocrine/paracrine
      effects of stretch are most probably due to release of factors from stretched
      cells.

PMID- 11471067
TI  - Effects of ischemia on the metabolism of cardiac enkephalins.
AB  - The effect of ischemia on cardiac Leucine enkephalin (Leu-enk) content,
      degradation and coronary release was studied in the isolated perfused hearts of
      male Sprague Dawley rats. Hearts were electrically stimulated at 180 beats/min.
      Cardiac Leu-enk concentrations were increased when hearts were perfused (635 +/-
      41 vs 301 +/- 60 fmol/g in control non-perfused hearts,) or during ischemia
      reperfusion (520 +/- 78 vs 277 +/- 42 fmol/g in heart submitted to ischemia
      alone). The quantity of leucine-enkephalin released by the heart during perfusion
      was four times higher than the initial content measured in the heart tissue. The
      rate of this release was the same throughout the experiment (25.9 +/- 2.9
      fmol/min/g during perfusion vs. 19.2 +/- 1.6 during ischemia-reperfusion). These
      findings suggested that cardiac enkephalin metabolism is regulated by cardiac
      events. In fact, enzymes involved in enkephalin degradation were decreased during
      perfusion (39%) and increased during ischemia (50%). The decrease in the enzyme
      activity during coronary perfusion depended on a reduced activity in the membrane
      fraction only while membrane and soluble fractions were interested in the
      increased enzyme activity after ischemia. Ischemia-reperfusion induced a larger
      release of Leu-enk than perfusion without ischemia. In view of the protective
      actions of enkephalin peptides against oxidative stress, we can infer from our
      results an implication of Leu-enk in ischemia-reperfusion and thus eventually in
      preconditioning phenomenon.

PMID- 11471068
TI  - Possible role of nitric oxide and arachidonic acid pathways in hypoxia-induced
      contraction of rabbit coronary artery rings.
AB  - In isolated coronary arteries, hypoxia induces an increase in tone by releasing
      an unidentified endothelium-derived contracting factor (EDCF). Isometric force
      was measured in an isolated rabbit coronary artery ring at 37 degrees C in
      control and high K+ (40 mM) pre-contracted conditions. Hypoxia (15 mmHg pO2)
      induced by equilibrating the perfusate with nitrogen. Hypoxia did not affect the
      resting tone but induced an endothelium-dependent contraction on pre-contracted
      rings. Inhibitors of nitric oxide (NO) were tested, L-NAME (10(-4) M) totally and
      L-NMMA (10(-4) M) partially convert the hypoxic contraction to an hypoxic
      relaxation. The addition of L-arginine (10(-4) or 10(-3) M) did not restore the
      response. Methylene blue (10( -5) M) and ODQ (1 H-[1,2,4] oxadiazolo-[4,3-a]
      quinoxalin-1-one, 10(-5) M), both inhibitors of guanylate cyclase, also changed
      the hypoxic contraction into a hypoxic relaxation. Catalase (1200 U/ml), which
      decomposes hydrogen peroxide (H2O2), and superoxide dismutase (150 U/ml, SOD), a
      free radical scavenger, did not change the hypoxic response but quinacrine (50
      microM), an inhibitor of phospholipase A2, significantly decreased it. Inhibitors
      of arachidonic acid metabolism (indomethacin, diethylcarbamazine, miconazole)
      however did not affect the hypoxic response. We conclude that in K+ pre
      contracted rabbit coronary artery rings, hypoxia induces a contraction which is
      nitric oxide and arachidonic acid dependent.

PMID- 11471069
TI  - Serotonin hypersensitivity in aorta of two kidney-two clip hypertensive rats:
      calcium contribution and prostanoids-nitric oxide interactions.
AB  - Previous studies from our own laboratory have shown that abdominal aorta rings
      from two kidney - two clip hypertensive rats (HT) develop hypersensitivity to
      serotonin (SER) which is related to a decreased nitric oxide (NO) availability
      and enhanced thromboxane A2 production. In the present study we investigated
      whether calcium and prostanoid-NO interactions are involved in these findings. To
      this purpose, the aortic responses to SER were analyzed in calcium-free medium
      and in calcium-depleted aorta placed in normal medium. Moreover, effects of
      ridogrel (RID, an antagonist of TxA 2/PGH2 receptors and inhibitor of thromboxane
      synthetase) were analysed by cumulative dose-response curves to SER in the
      presence and in the absence of the NO synthase inhibitor N(omega)-nitro-L
      arginine (NOLA). Vascular responses to SER in vessels from HT rats were
      associated with increased intracellular calcium mobilization. In addition,
      hypersensitivity to SER in HT group respect to sham group (SH) disappeared in the
      presence of RID, NOLA and RID plus NOLA. RID decreases the maximum tension to SER
      and this effect was prevented by NOLA. This inhibition was of a greater magnitude
      in rings from sham rats (SH): 34 +/- 6% than in HT rats: 15 +/- 6% (p < 0.05).
      Besides, RID decreased the sensibility to SER in the presence of NOLA only in the
      HT group. In conclusion, the present study suggests that SER hypersensitivity
      observed in HT rats is related to a facilitated intracellular calcium
      mobilization and enhanced TxA2-endoperoxide response. Changes in membrane SER
      gated calcium channels opening are observed only during the early hypertensive
      period. Besides, the lower depressor effect of RID on the maximal tension to SER
      in aorta rings from HT rats are related with a decreased NO availability in this
      model of renovascular hypertension.

PMID- 11471070
TI  - Nutrient sensing, leptin and insulin action.
AB  - The glucose-fatty acid cycle as proposed four decades ago by Randle suggests that
      insulin resistance develops in consequence of alterations of the metabolic
      pressure of lipids. The more recently published 'hexosamine pathway theory' and
      the 'malonyl-CoA hypothesis' depict insulin resistance as a consequence of an
      imbalance between utilization of lipids and carbohydrates. The latter is finely
      tuned by entry of fatty acids into the mitochondria and/or by entry of glucose to
      the hexosamine pathway. A significant body of evidence has also been accumulated
      which points to the complex effects of leptin, an adipocyte-derived signal of
      lipid stores, on the storage and metabolism of fats and carbohydrates. These are
      mediated either directly, through actions on specific tissues, or indirectly, via
      CNS, endocrine and neural mechanisms. The available literature also provides good
      evidence that leptin orchestrates the metabolic changes in a number of organs and
      tissues, and alters nutrient fluxes to favor energy expenditure over energy
      storage. In this article, the proposed lipopenic effects of leptin as studied in
      various animal models of diet-induced insulin resistance, and possible
      regulations of leptin production and action by marine fish oil feeding are
      reviewed.

PMID- 11471071
TI  - IRS-1 tyrosine phosphorylation reflects insulin-induced metabolic and mitogenic
      responses in 3T3-L1 pre-adipocytes.
AB  - We determined the involvement of Tyr-1158 within the regulatory loop of the
      insulin receptor (IR) in the generation of insulin-specific responses in situ.
      For this purpose chimeric receptors with an epidermal growth factor (EGF)
      receptor extracellular domain and an IR cytoplasmic domain (EIR) were
      constructed, which allow activation of the cytoplasmic IR domain without
      activation of endogenous wt-IRs. Tyr-1158 of the chimera EIR was exchanged for
      Phe, creating a mutant chimeric receptor (EIR-Y1158F). Chimeric receptors were
      expressed in 3T3-L1 pre-adipocytes, which do not show insulin-specific responses
      upon EGF stimulation. We found that pre-adipocytes expressing EIR-Y1158F were
      impaired in their ability to stimulate glycogen synthesis and DNA synthesis upon
      maximal stimulation with EGF. EIR-Y1158F was impaired in its ability to
      phosphorylate insulin receptor substrate (IRS)-1 and induce downstream signals of
      IRS-1 phosphorylation, such as the association of IRS-1 with phosphatidyl
      inositol-3'-kinase and the activation of protein kinase B (Akt). In contrast with
      the phosphorylation of IRS-1, the phosphorylation of IRS-2 and extracellular
      regulated protein kinase-1/-2 was normal in EIR-Y1158F expressing cells. These
      observations suggest that the level of IRS-1 phosphorylation rather than the
      level of IRS-2 phosphorylation mediates insulin-induced glycogen synthesis and
      DNA synthesis in 3T3-L1 pre-adipocytes.

PMID- 11471072
TI  - Leptin perfusion affects insulin secretion but not insulin receptors in rats.
AB  - The aim of the study was to investigate acute leptin effects on insulin secretion
      and liver insulin binding in rats in vitro. In the in situ experiments leptin
      changed the pattern of insulin secretion from the pancreas but did not influence
      insulin binding in the liver. Perfusion of the pancreas with leptin (1, 10, and
      100 nmol/l, respectively) at physiological and supraphysiological levels of
      glucose (6.66 and 25.0 mmol/l, respectively) did not evoke the inhibition of
      insulin output observed by the authors previously in the in vivo manners. On the
      contrary, leptin perfusion resulted in stimulation of insulin secretion.
      Simultaneously, liver perfusion with leptin for 30 min did not influence specific
      insulin binding. Analysis of Scatchard's plots indicated no changes in the number
      of high- and low-affinity insulin receptors and in their affinity to the hormone.
      Additionally, leptin did not influence general carbohydrate and lipid metabolism
      of the perfused liver. After the treatment with leptin, the output of glucose,
      free fatty acids and triglycerides to perfusate and the final contents of
      glycogen and triglycerides in liver were comparable to values obtained in control
      animals. The results indicate that some in vitro effects exerted by leptin differ
      from those observed in vivo.

PMID- 11471073
TI  - The mitogenic activity of endothelin-1 on megakaryocytopoiesis in vitro.
AB  - Endothelin (ET)-1 induces proliferation of various cells including smooth muscle
      cells, fibroblasts, glomerular mesangial cells, endothelial cells and
      osteoblasts. ET-1 also stimulates synthesis of interleukin (IL)-6 in endothelial
      and bone marrow stromal cells of rat. It is well known that IL-6 modulates
      megakaryocytopoiesis. Some studies have indicated that megakaryocytes express
      both ET receptors and they are targets for ET. Therefore we planned to examine
      the effects of ET-1 on the growth of normal megakaryocytic cells in rat bone
      marrow primary cell culture. Bone marrow cells were cultured at 37 degrees C, in
      an incubator atmosphere of 5% CO2 in air and 95% relative humidity for nine days.
      ET-1 at 10(-7), 10(-8 ) and 10(-11) M, and control with saline were added at the
      beginning of the experiment protocol. At each day, plasma clots were stained
      using direct-coloring thiocholin method for acetylcholinesterase activity.
      Although 10(-7) M ET-1 did not change the proliferation of megakaryocytic cells,
      this could be due to the presence of over crowded fibroblasts in the same
      environment. 10(-8) M ET-1 stimulated megakaryocytic cell growth to 234% over the
      control on the fifth day. ET-1 at a concentration of 10(-11) M also rised the
      megakaryocytic cell number significantly reaching up to 86% at the sixth day. Our
      results indicate that ET-1 may modulate the growth of megakaryocytic cells by an
      autocrine and/or paracrine action.

PMID- 11471074
TI  - Presence of HLA-DR immunopositive cells in human fetal thymus.
AB  - Several kinds of thymic cells express MHC class II antigens, including human
      leukocyte-associated antigen-DR (HLA-DR) during postnatal development. The
      present study was focused on the detection and analysis of HLA-DR
      immunoreactivity in human fetal thymuses (6-7th month of gestation). Using
      monoclonal antibodies, indirect immunoperoxidase staining (IIP), immunogold
      electron microscopy (IGEM), enzyme-linked immunosorbent assay (ELISA) and flow
      cytometry, HLA-DR immunopositive (IP) thymic cells were found in samples studied.
      IIP and IGEM demonstrated the presence of HLA-DR IP stromal cells (SCs):
      epithelial cells (ECs), dendritic-like cells (DCs) and macrophages (MCs) as well
      as HLA-DR IP lymphocytes (Lys) in all thymic regions. HLA-DR immunoreactivity was
      more prominent in the medullary ECs (mECs) than in the cortical ECs (cECs).
      Strong staining of Hassall's corpuscles and the adjacent mECs was seen. The
      differences in the intracellular distribution of HLA-DR molecules were detailed
      by IGEM as a first attempt to analyse HLA-DR IP cells at ultrastructural level.
      ELISA data and two-colour flow cytometric analysis revealed the presence of HLA
      DR IP and HLA-DR/CD3 double IP Lys in accordance with the immunocytochemical
      assays. The results presented enrich the information about HLA-DR IP components
      of the thymic microenvironment in developing human thymus and raise the question
      of their role during prenatal T cell differentiation and selection processes.

PMID- 11471075
TI  - Age-related changes in the synapses of the rat's neostriatum.
AB  - By means of transmission electron microscopy, the age-related changes in
      axospinous (ASS) and axodendritic (ADS) synapses in the dorsal part of the
      rostral neostriatum in two groups of Wistar rats: young (3-month-old), and
      senescent (25-month-old) were examined. The changes in different parameters,
      characterizing the ASS and ADS: synaptic density (SD), number of synaptic
      vesicles (SV), number of synaptic contact zone (SCZ), and number of dendritic
      spines, bearing synapses (DS) were investigated morphometrically. The SD of the
      ASS decreased significantly during aging, but the SD of the ADS did not changed
      significantly. The mean area of the synaptic boutons increased significantly
      during aging in two types of synapses. The mean number of vesicles per synaptic
      bouton increased, but the number of vesicles per microm2 of synaptic bouton, and
      per microm3 of the neuropil decreased. The mean SCZ length increased in both
      types of synapses. The total SCZ length per 1000 microm2 of the neuropil, and the
      total area of the SCZ per 1000 microm3 of the neuropil decreased in ASS, but the
      same parameters of the ADS did not changed significantly. The mean number of
      synaptic DS per 1000 microm2 of the neropil decreased during aging, but the mean
      area of the synaptic DS increased. The present results support the hypothesis
      that the synaptic contacts change significantly during aging, and the ASS are
      more vulnerable during aging than the ADS.

PMID- 11471076
TI  - Taurine protects against carbon tetrachloride toxicity in the cultured neurons
      and in vivo.
AB  - Carbon tetrachloride (CCl4) has been found to induce cellular damage by
      generating oxygen free radicals. A study was carried out to investigate the
      effects of taurine (extracted from Pegasus laternarius Cuvier) on CCl4
      intoxicated cultured neurons. CCl4 application (0.4 mmol x l(-1), 0.8 mmol x l( 
      1), 1.2 mmol x l (-1) and 1.6 mmol x l(-1 )) increased the lipid peroxidation
      product and decreased glutathione peroxidase (GPx) activity significantly in a
      concentration dependent manner. Pretreatment of cultures with taurine (10
      micromol x l(-1), 30 micromol x l(-1) and 60 micromol x l(-1)) prevented the loss
      of GPx activity and lipid peroxidation. The effects of three different dosages of
      taurine (10 mg/kg body wt., 20 mg/kg body wt. and 40 mg/ kg body wt.) for 45 days
      on the activities of superoxide dismutase and glutathione peroxidase were
      examined in the cerebrum, cerebellum and medulla of normal and CCl4 treated mice.
      Treatment of mice with taurine provided protection against CCl4 toxicity as was
      evident by lipid peroxide status. Taurine was not so successful at inducing the
      activity of SOD in normal animals except in the medulla where it could increase
      the activity of SOD (p < 0.05). Taurine induces the GPx activity in a dose
      dependent manner in all regions of the brain studied. Also in the CCl4 poisoned
      mice taurine could augment the status of GPx activity in a dose dependent manner.
      Hence it is concluded that taurine can protects neurons from the oxidative stress
      induced by CCl4.

PMID- 11471077
TI  - Trial of the Trachoma Rapid Assessment methodology in The Gambia.
AB  - PURPOSE: To test the validity and repeatability of a newly designed Trachoma
      Rapid Assessment (TRA) methodology. METHOD: Results from an initial TRA in 20
      villages (TRA1) are compared with those of a second validation TRA (TRA2) after 6
      weeks in 13 villages, randomly selected out of the original 20, conducted by
      different field staff. Findings of TRA1 and TRA2 are compared with those of a
      door-to-door survey of the entire population of all 13 villages. RESULTS: There
      is a considerable amount of variation between the results of TRA1 and TRA2 and
      between the results of both TRA's and the door-to-door survey. Even indicators
      that should have remained the same, like distance to Primary Health Centre or
      distance to trichiasis surgery facility, scored differently. CONCLUSIONS: The TRA
      methodology is easy to use and the results are quickly available. The scoring
      system indicates which intervention(s) of the SAFE strategy are needed and
      facilitates priority setting. The definition of some indicators, like
      availability and use of latrines, may need modification. In some cases, the
      scoring system seems to exaggerate differences between the actual findings. The
      consistency between two TRA's in the same village is low and the accuracy in
      measuring the actual situation is doubtful.

PMID- 11471078
TI  - Rapid assessment of trachoma prevalence--Singida, Tanzania. A study to compare
      assessment methods.
AB  - This article presents a methodology for the rapid assessment of trachoma that was
      validated against a prevalence survey, undertaken simultaneously in the same 12
      villages in central Tanzania. The rapid assessment protocol suggests examinations
      for active trachoma in 50 children ages 1-10 in at least 20 households chosen
      from the high-risk neighborhoods in each village. Women over the age of 15 in the
      same households were examined for trichiasis. In the rapid assessment, 244
      households were visited, with 691 children and 470 women examined. In the
      prevalence survey, 377 households were visited, with 1855 children and 1310 women
      examined. Rankings of the villages using population prevalence of active disease
      and rapid assessment prevalence of active disease are highly correlated (Spearman
      correlation = 0.59, p < 0.05). In fact, the three villages with the highest
      prevalence in the population data were identified as the villages with the
      highest prevalence by the rapid assessment. Although rankings of the villages
      using population prevalence of trichiasis and rapid assessment prevalence of
      trichiasis are positively correlated, this correlation is not significantly
      different from zero, the village with the highest trichiasis prevalence according
      to the random sample being ranked as 8th by the rapid assessment. The cost of the
      rapid assessment was roughly one-third the cost of the prevalence survey. Thus,
      it appears that the rapid assessment method can quickly and inexpensively
      determine which villages have the greatest amount of active disease in children,
      and roughly estimate the burden of trichiasis in the community.

PMID- 11471079
TI  - Assessment of trachoma prevalence in a mobile population in Central Australia.
AB  - Trachoma is reported to be hyperendemic in Australia. This study was conducted in
      a desert area of Central Australia to implement and evaluate the WHO SAFE
      strategy to control trachoma. The aim of the study was to obtain baseline
      trachoma prevalence data and to determine whether a single annual visit is
      adequate for a treatment program targeting households with active cases in a
      highly mobile population. All registered residents of two Aboriginal communities
      were eligible for examination. Four visits over the course of 13 months were made
      to the communities for ocular examinations of residents present at the time of
      the visit. Examination, diagnosis, and grading of trachoma followed WHO
      guidelines. The overall examination rate was 75%, refusal rate was <1%, but
      approximately 50% of community residents were absent during the examination
      period. Prevalence varied on each visit, but the overall prevalence of active
      trachoma was 49% over the 13-month period. Children less than 10 years of age had
      the highest prevalence of active trachoma (79%), over the course of the 13
      months, yet the prevalence at any one visit was approximately 60%. Trachomatous
      scarring was present in 23% of the population. These results suggest that many
      cases of active trachoma may be missed if a prevalence survey is conducted at
      only one point in time. Multiple examinations should be conducted to adequately
      establish prevalence in the population. Antibiotic treatment and health promotion
      campaigns need to be developed in consideration of local community dynamics.

PMID- 11471080
TI  - Pooling of Chlamydia laboratory tests to determine the prevalence of ocular
      Chlamydia trachomatis infection.
AB  - With the Global Elimination of Trachoma by 2020 program underway, it has become
      increasingly important to identify the prevalence of ocular chlamydia infection
      in communities. DNA amplification tests are the gold standard, but are
      prohibitively expensive. In the present paper, we investigate whether pooling
      multiple specimens into a single test is feasible. The conjunctivae of 170
      children in western Nepal were examined and swabbed. The prevalence of chlamydial
      infection was estimated in two ways using the ligase chain reaction: by testing
      all 170 specimens individually, and by testing 34 pools of 5 specimens each. We
      show that the confidence interval for 34 pooled specimens approaches that of
      doing all 170 specimens as the prevalence decreases. We also determine the
      optimal number of specimens to pool into a single test to minimize the confidence
      interval of the estimate. If the population prevalence is expected to be around
      10%, then 14 specimens should be pooled per test. Even at 50% prevalence, costs
      can be reduced by pooling two samples per test.

PMID- 11471081
TI  - Prevalence of trachoma and its determinants in Dalocha District, Central
      Ethiopia.
AB  - AIM: This community-based cross-sectional study was conducted to determine the
      prevalence of trachoma in Dalocha District, Central Ethiopia. METHODS: A
      multistage sampling method was used to identify the peasant associations and
      households included in the study. The WHO clinical grading method for trachoma
      was used. RESULTS: Of the 619 sampled persons, 302 (48.8%) males and 317 (51.2%)
      females, 564 people were available for examination, yielding a response rate of
      91.1%. More than half (51.1%) of the children aged 10 years or less had active
      trachoma (trachomatous inflammation, TI, in 16.5% and trachomatous follicles, TF,
      in 34.6%). On the other hand, active trachoma and trachomatous trichiasis (TT)
      were each found in 5.5% of individuals older than 10 years of age. CONCLUSIONS:
      According to the WHO, the findings of TI and TF in more than 5% and 20%,
      respectively, of children aged 10 years or less and TT in more than 1% of older
      individuals indicate that trachoma is a major public health problem in Dalocha
      community.

PMID- 11471082
TI  - OmpA genotypic evidence for persistent ocular Chlamydia trachomatis infection in
      Tanzanian village women.
AB  - BACKGROUND: Trachoma is still a significant problem in the developing world.
      Adult women are at higher risk of developing scarring and trichiasis, the
      potentially blinding sequelae, compared to men. In part, the higher risk may be
      due to more frequent infections in women because of their frequent contact with
      children, the main reservoir of C. trachomatis infection. However, other factors
      associated with infection, particularly constant infection, in adult women need
      to be identified. METHODS: A group of 118 women who were infected with C.
      trachomatis and 118 women who were not infected, but of similar age and trachoma
      status, were identified in 1996 from a population-based sample of women age 16
      and older from eleven villages in Kongwa, Tanzania. This group of 236 was re
      contacted three years later to ascertain trachoma status and determine infection
      status using polymerase chain reaction-enzyme immunoassay (PCR-EIA). Positive
      samples at both time points were examined for serovar and genotype shift, using
      ompA sequencing information. RESULTS: Of the original 236 women, 165 (70%)
      completed exams in 1999. Fifty-eight (35%) of the 165 women were excluded from
      this analysis because they received antibiotic treatment for trachoma in the six
      months prior to the second exam. Infection at baseline was the most important
      predictor of infection three years later (Age-adjusted odds ratio (95% confidence
      interval) 6.6 (1.8-24.4)). A total of 17 women (16%) were infected at the two
      examinations, and of the 15 for whom genotyping could be done, 11 (73%) were
      infected with the same ompA genotype at both time points. Chronically infected
      women were more likely to have trichiasis, scarring, and active trachoma at
      baseline than those never infected or infected only once. Only 41% of the
      chronically infected women were living in houses with infected pre-school
      children, but 24% were in houses with no children. Four of ten women with
      trichiasis developed incident corneal opacity over the three years. CONCLUSIONS:
      The data provide evidence for persistence of infection in a sub-group of women.
      The strongest predictor of infection at follow-up was baseline infection, and
      most were infected with the same genotype at both time points. For women with
      persistent infection, at least half were either not living with children or not
      living with infected children, suggesting that continual re-exposure from a close
      family member was less likely. Chronic infection is likely related to both
      exposure and immunological factors, and these need to be further identified.
      Inclusion of women in community-based treatment programs, regardless of whether a
      child is present in the house, is likely to be important in preventing the
      progression of inflammatory trachoma and scarring to trichiasis.

PMID- 11471083
TI  - Progression of active trachoma to scarring in a cohort of Tanzanian children.
AB  - Risk factors for the incidence of scarring are needed to inform trachoma control
      programs in countries hyperendemic for this blinding disease. A cohort of pre
      school children with constant, severe trachoma, and an age, sex, and neighborhood
      matched cohort of children without constant severe trachoma were followed for
      seven years to determine the incidence of scarring. The incidence of scarring in
      the children with constant severe trachoma was 29.2% versus 9.6% in the
      comparison group. In a model adjusting for multiple factors, significant
      predictors of scarring were increasing age, female, and constant severe trachoma
      (OR = 4.85, 95% CL = 2.05, 11.40). Infection with C. trachomatis at follow up was
      also associated with scarring in both groups of children. It is likely that these
      children have a different host response to infection, and represent a subgroup at
      high risk for the blinding complications of trachoma. Reducing exposure to
      infection in the community through antibiotics and changes in hygiene practices
      is still the most promising control strategy.

PMID- 11471084
TI  - Reduction of trachoma in the absence of antibiotic treatment: evidence from a
      population-based survey in Malawi.
AB  - PURPOSE: A survey was conducted in Chikwawa District, Malawi in order to compare
      the current prevalence of trachoma with a similar survey in 1983. METHODS: Using
      random cluster household sampling, children aged 1 to 6 and adults aged 50 or
      older were enumerated and examined for the presence of trachoma. RESULTS: Among
      the 1313 children enumerated, 1249 (95.1%) were examined and among the 1431
      adults enumerated, 1221 (85.3%) were examined. The prevalence of active trachoma
      among the children was 13.9% (11.9-15.9%), 10.0% in males and 14.4% in females.
      The prevalence of active trachoma varied significantly among the 25 clusters,
      ranging from 3.9% to 38.2% with 5 clusters (20%) having a prevalence >20%. Signs
      of trachomatous trichiasis were observed in 1.0% of adults examined. Active
      disease in 1999 was associated with a longer distance to the primary water
      source. CONCLUSIONS: Since 1983 there has been no mass antibiotic treatment
      programme in the district and little change in socioeconomic status. However,
      compared to the 1983 findings, active trachoma has been reduced by over 50% (p <
      0.001) and trachomatous trichiasis by over 80%. In the 16-year interim
      (especially in the past 7 years) health, water and hygiene programmes were
      initiated and we hypothesize that the reduction in active disease is likely due
      to these changes. Our findings suggest that sustained reductions in active
      trachoma can be achieved without community-based antibiotic distribution.

PMID- 11471085
TI  - Recurrence of trichiasis: a long-term follow-up study in the Sultanate of Oman.
AB  - BACKGROUND: The prevalence of long-term trichiasis recurrence following tarsal
      rotation and electro-epilation procedures has not been determined. A non
      concurrent prospective study of surgical cases of trichiasis was therefore
      undertaken in Oman. METHODS: A sample of 603 surgical cases of trichiasis
      (approximately half tarsal rotation and half electro-epilation) was followed for
      an average of 3.1 years to determine recurrence. Recurrence was defined as either
      mild (<5 lashes touching the globe) or severe (5 or more lashes touching the
      globe). RESULTS: Overall, 56% (95% confidence interval of 50.6%-61.0%) of all
      surgical cases recurred; ranging from 61.8% of tarsal rotation patients to 50.6%
      of electro-epilation patients. Severe recurrence was detected among 27% of tarsal
      rotation patients and 10% of electro-epilation patients. Recurrence was
      associated with female sex, residence in a high-risk region, and time since
      surgery. DISCUSSION: The risk of recurrence after electro-epilation and
      bilamellar tarsal rotation surgery is high; strategies that account for
      recurrence need to be introduced.

PMID- 11471086
TI  - Understanding the community perspectives of trachoma: The Gambia as a case study.
AB  - Trachoma has justifiably attracted an incredibly large amount of research
      interest and literature over the last several decades. Perhaps, the area which is
      least explored is the social aspect of the disease. Most of the major constraints
      to trachoma control on the global scale appear to be concerned with this aspect
      of the disease. Recently, a study was conducted in The Gambia with the aim of
      highlighting the socio-cultural determinants of trachoma. We applied qualitative
      methods of Focus Group Discussion and Semi-structured interview to explore the
      local people's concepts of the disease among two traditional ethnic groups, the
      Jolas and the Manjagos, in five rural communities. Our results show that there
      appears to be a poor understanding of the chronic nature of the active
      inflammatory phase of trachoma among the local people. But more importantly,
      there is a lack of mental connection between this childhood infection and
      blindness resulting from trichiasis in adults. This probably explains why it is
      difficult for the people in these communities to see the need for prolonged use
      of antibiotic eye ointment as required in the treatment of active inflammatory
      trachoma. Moreover, the local concepts about the cause(s) of the disease tend to
      compel the people to seek the traditional herbal remedies first, though there is
      adequate knowledge and experience among them that modern methods of treatment may
      produce cure, as in the case of corrective lid surgery for trichiasis. This
      ambivalent attitude of the people to health services appear to be a universal
      phenomenon in many local communities in Africa, and perhaps hinges on the local
      people's perspective of the disease, which varies from place to place. We
      conclude that for any intervention strategy to achieve the set goals of
      eliminating trachoma in spite of these constraints, community support and
      participation is essential, and in order to achieve this, the health care
      provider needs to have a better understanding of the community perspectives of
      the disease.

PMID- 11471087
TI  - Magnitude of trachoma and barriers to uptake of lid surgery in a rural community
      of northern Nigeria.
AB  - AIMS: A population-based cross-sectional survey for trachoma prevalence was
      conducted in a subdistrict of northern Nigeria. The objectives of the survey were
      to determine the magnitude and pattern of trachoma and the barriers to uptake of
      lid surgery in the area. METHODS: A total of 2903 people of all ages were
      examined out of 3715 registered eligible persons. The study population was chosen
      by a two-stage cluster random sampling technique. Each person was examined for
      signs of trachoma. The World Health Organization (WHO) simplified trachoma
      grading was used. Persons with trichiasis that had not attended hospital were
      asked why they had not sought hospital treatment. RESULTS: A blindness prevalence
      of 1.5% (95% CI 0.4%-2.7%) was found in the study population. About 20% of the
      blindness were due to trachoma. The prevalence of trichiasis among women 15 years
      and above was found to be 8.6% (95% CI 6.8%-10.7%). The prevalence of active
      trachoma among children was 11.8% (95% CI 10.1%-13.3%). Over 90% of people with
      trichiasis have not sought medical attention. The major identified factor that
      prevents people from accessing hospital treatment for trichiasis was cost (57%).
      CONCLUSION: This study suggests that trachoma is of public health significance in
      this area; as such, an effective trachoma control program with emphasis on lid
      surgery should be established.

PMID- 11471088
TI  - Epidemiological, demographic, and economic analyses: measurement of the value of
      trichiasis surgery in The Gambia.
AB  - AIM: Untreated trichiasis can lead to corneal opacity. Surgery to prevent the
      eyelashes from rubbing against the cornea is available, but many individuals with
      trichiasis never undergo the operation. This study estimates the cost of illness
      of untreated trichiasis and the willingness to pay for surgery and compares them
      with the actual cost of providing surgery. MATERIALS AND METHODS: The cost of
      illness estimate is based on trichiasis patient demographics. Data on the
      implicit price of obtaining surgery and surgical utilization in a matched pair
      randomized trial are used to infer individual willingness to pay for trichiasis
      surgery. Patients in the study paid nothing out-of-pocket for surgery; the price
      of obtaining surgery is the value of the individual's time needed for travel and
      surgery plus the price of public transportation. The cost of producing surgery
      was calculated from project records. RESULTS: All monetary figures are reported
      in 1998 US dollars. The average cost of untreated trichiasis, or the net present
      value of life-time lost economic productivity, was $89. Individuals facing a
      lower cost were more likely to undergo an operation; the inferred average
      willingness to pay was $1.43 (SD 0.244). Surgery cost $6.13 to provide, including
      $0.86 for transportation to the village. DISCUSSION: Whether the value of
      trichiasis surgery exceeds the cost in The Gambia depends on how the value is
      measured. Individuals are willing to use only limited resources to obtain surgery
      even though lifetime economic productivity may increase substantially. All three
      economic measures can be used to inform policy.

PMID- 11471089
TI  - The SAFE strategy for trachoma control: planning a cost-effectiveness analysis of
      the antibiotic component and beyond.
AB  - AIM: A limited literature addresses the cost-effectiveness of the prevention and
      treatment of trachoma and its sequelae. The literature focuses on government
      costs. This paper motivates the inclusion of and details methods for measuring
      the costs for the target population. METHODS: Costs to the targeted population
      can be measured while studying efficacy or effectiveness. These costs can be
      added to the more frequently measured costs to the government to calculate costs
      for the entire society. This section indicates the types of costs to consider,
      refines the concept of costs, describes the necessary data, outlines how the
      methods of data collection fit with the methods that would be employed for a
      general effectiveness study, and describes the appropriate calculation of a cost
      effectiveness ratio. RESULTS: The costs to the targeted population can be
      measured with few additional resources. Placing a value on villagers' time or
      translating clinical results into summary, preference-based health-related
      quality of life measures would increase the resources required more
      substantially. DISCUSSION: For theoretical and practical reasons, future cost
      effectiveness analyses of the full SAFE strategy and the antibiotic component of
      the strategy should be done from a perspective that includes both the government
      and the targeted population. This can be useful in policy making and increase our
      understanding of reasons for less than universal participation.

PMID- 11471090
TI  - Military laser weapons: current controversies.
AB  - Military laser weapons systems are becoming indispensable in most modern armies.
      These lasers have undergone many stages of development, and have outpaced
      research on eye protection measures, which continue to have inherent limitations.
      Eye injuries caused by military lasers are increasingly reported, leading to
      speculation that these would become an important cause of blinding in modern
      conflicts. As part of the effort to ban inhumane weapons, international laws have
      been passed to restrict the proliferation of such blinding weapons. However,
      there are controversies concerning the interpretation, implementation and
      effectiveness of these laws. The ophthalmic community can play a greater role in
      highlighting ocular morbidity from military lasers, and in preventing their
      further proliferation.

PMID- 11471091
TI  - Familial clustering and myopia progression in Singapore school children.
AB  - BACKGROUND: Familial factors may be related to the progression of myopia in
      children. A cohort study was conducted to determine the relationship between
      familial factors and myopia progression in children. METHODS: From a larger
      clinical trial (n = 311), 153 Singapore children aged 6--12 years were recruited
      to participate in a cohort study of the risk factors for myopia progression. An
      in-person interview was conducted whereby information on the history of myopia in
      first-degree relatives was obtained. Other information collected included housing
      type, parental education and income. Cycloplegic refractive error as measured by
      subjective refraction and autorefraction were ascertained every six months. The
      average length of follow-up was 28 months. RESULTS: The adjusted mean rate of
      progression of myopia was -0.60 (95% confidence interval -0.66, -0.55) diopters
      per year. The average rate of progression of myopia for children with a parental
      history of myopia was -0.63 (95% confidence interval -0.69, -0.56) diopters per
      year compared to -0.42 (95% confidence interval -0.57, -0.27) diopters per year
      for children whose parents were not myopic. The different measures of family
      history of myopia were related to rate of change in refractive error and
      refractive error in the final visit. There was no association between close work
      and myopia progression. CONCLUSIONS: A positive family history is related to the
      progression of myopia and final refractive error in Singapore children, thus
      supporting evidence that hereditary factors may play an important role in myopia
      progression.

PMID- 11471092
TI  - Associations of cardiovascular disease and its risk factors with age-related
      macular degeneration: the POLA study.
AB  - The POLA study (June 1995 through July 1997) is a population-based study on
      cataract and age-related macular degeneration (AMD) and their risk factors in
      2584 residents of Sete (South of France), aged 60--95 years. Classification of
      AMD was performed on 50 degrees fundus photographs, according to an international
      classification. The presence of cardiovascular disease and its risk factors was
      determined by interviewer-based questionnaire, clinical examination
      (anthropometry, blood pressure) and fasting plasma measurements. Using a logistic
      model adjusted for age and gender, late AMD was not significantly associated with
      a history of cardiovascular disease, diabetes, use of hypocholesterolemic drugs,
      hypertension, blood pressure or plasma lipids. Obese subjects (body mass index
      greater than 30 kg/m( 2)) had a 2.29-fold (95% confidence interval (CI): 1.00-
      5.23) and 1.54-fold (CI: 1.05--2.26) increased risk of late AMD and pigmentary
      abnormalities in comparison with lean subjects. Finally, the risk of soft drusen
      was decreased in those subjects with a history of cardiovascular disease (odds
      ratio (OR) = 0.72, CI: 0.54--0.97), and increased with increasing levels of HDL
      cholesterol (OR = 1.52, CI: 1.14--2.02). None of these results were modified by
      further adjustments for smoking, educational level and plasma alpha-tocopherol.
      These results need to be confirmed by other studies, which ideally should be
      longitudinal and prospective.

PMID- 11471093
TI  - Measures of obesity and age-related eye diseases.
AB  - OBJECTIVE: To compare body mass index with waist-to-hip ratio as correlates of
      age-related eye disease. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: Participants of the Beaver Dam Eye Study at 5-year follow-up
      examinations. METHODS: Body mass index was computed from weight and height, and
      waist-to-hip ratio was computed from measurements all done at the 5-year
      examination. Presence of ocular lesions was based on gradings of standard
      photographs of the retina and lens. MAIN OUTCOME MEASURES: Presence of early and
      late age-related maculopathy and nuclear, cortical, and posterior subcapsular
      cataracts. RESULTS: In women, early age-related maculopathy was significantly
      associated with both body mass index and waist-to-hip ratio. The relationship
      between waist-to-hip ratio and late age-related maculopathy was of borderline
      significance. When analyzed as continuous measures, waist-to-hip ratio was more
      strongly associated with nearly every outcome compared to body mass index. In
      men, there was little difference between body mass index and waist-to-hip ratio
      as correlates of age-related eye diseases. The reason for differences between men
      and women is not clear, but is unlikely to be due to current exposure to
      estrogen. CONCLUSIONS: In women in our analyses, waist-to-hip ratio is more
      strongly associated with age-related eye disease than is body mass index. When
      adiposity is considered as a risk factor itself, or as a confounder of risk
      factors for age-related ocular disease, waist-to-hip ratio may be the better
      measure to use in women.

PMID- 11471094
TI  - Trial of Trachoma Rapid Assessment in a subdistrict of northern Nigeria.
AB  - PURPOSE: To assess the usefulness of Trachoma Rapid Assessment (RA) in priority
      ranking of trachoma areas. METHODS: RA was conducted concurrently with a cross
      sectional trachoma prevalence survey in some villages selected from the
      communities at risk for trachoma in the Kaita Local Government Area of northern
      Nigeria. The RA team consisted of two ophthalmic nurses. Pen torches and loupes
      were used for the examination. Data were collected on the seven components of the
      RA 'information pyramid' for all the selected villages. The data were analyzed
      using the RA methodology guidelines to determine the priority villages for
      trachoma intervention. This was compared with the ranking from the cross
      sectional trachoma prevalence survey. RESULTS: The results of RA were found to be
      in agreement with the cross-sectional survey in 53.3% of the villages in the
      priority ranking of trichiasis, while in the priority ranking of active trachoma
      the agreement between the two methods was found to be 60%. The risk factors for
      trachoma were shown to be of high magnitude in all the villages using both the RA
      method and the prevalence survey. CONCLUSION: RA may be a more useful tool when
      applied to a vast area where the risk of trachoma is likely to differ greatly
      between different parts of the area. In the determination of the trichiasis
      pattern of a community by RA, it may be more useful to use the actual number of
      trichiasis cases in the area rather than the prevalence of trichiasis. The
      operational definition of some risk factor indicators seems very subjective and
      vague. The RA method needs more validation to sharpen the indicators used.

PMID- 11471095
TI  - Macrophage inflammatory protein-1alpha (not T helper type 2 cytokines) is
      associated with severe forms of respiratory syncytial virus bronchiolitis.
AB  - It has been suggested that the pathogenesis of respiratory syncytial virus (RSV)
      infection is related to the development of T helper (Th) type 2 cytokine
      responses. The presence of Th1 and Th2 cytokines and the chemokines macrophage
      inflammatory protein (MIP)-1alpha and monocyte chemotactic protein (MCP)-1 were
      assessed by ELISA in nasopharyngeal secretions of infants with RSV infection.
      Infants with mild bronchiolitis had increased Th1 cytokines and reduced Th2
      cytokines, compared with infants with upper respiratory tract illness alone.
      Severe bronchiolitis was characterized by a more balanced Th1-Th2 response that
      did not differ from that of infants with upper respiratory tract illness alone.
      In contrast, MIP-1alpha was markedly increased in infants with severe
      bronchiolitis. MIP-1alpha and MCP-1 levels also were inversely related to oxygen
      saturation (P<.005). Thus, the severity of RSV bronchiolitis appears to be
      related more to chemokine release than to Th2 cytokine production.

PMID- 11471096
TI  - The presence of a newly identified infectious agent (SEN virus) in patients with
      liver diseases and in blood donors in Japan.
AB  - The existence of the newly discovered SEN virus (SENV) was investigated in 379
      Japanese patients with liver diseases and in 277 blood donors, to determine
      whether SENV is associated with non-A-E hepatitis. SENV DNA was detected by
      seminested polymerase chain reaction, with primers directed to 2 SENV strains:
      SENV-H and SENV-D. SENV was detected in 7 (32%) of 22 patients with fulminant
      hepatitis, in 15 (17%) of 86 patients with acute hepatitis, in 38 (27%) of 139
      patients with chronic hepatitis, in 29 (31%) of 93 patients with liver cirrhosis,
      in 5 (33%) of 15 patients with autoimmune hepatitis, in 11 (46%) of 24 patients
      with primary biliary cirrhosis, and in 27 blood donors (10%). Infection occurred
      more frequently in patients with liver diseases than in blood donors; however,
      there were no significant differences in SENV-positive rates between patients
      with non-A-C hepatitis and those with acute or chronic hepatitis due to known
      hepatitis virus or nonviral liver disease. This study did not suggest SENV as a
      possible causative agent of non-A-C hepatitis.

PMID- 11471097
TI  - A randomized, controlled trial to determine whether continued ribavirin
      monotherapy in hepatitis C virus-infected patients who responded to interferon
      ribavirin combination therapy will enhance sustained virologic response.
AB  - This study assessed the use of ribavirin monotherapy to enhance sustained
      virologic response in hepatitis C virus (HCV)-infected patients who achieved
      virologic response to interferon (IFN)-ribavirin combination therapy. Patients
      who had chronic HCV infection and prior relapse were retreated with IFN-ribavirin
      for 6 months. Patients with an end-of-treatment virologic response were assigned
      randomly to either stop use of both IFN and ribavirin or to continue use of
      ribavirin as monotherapy for an additional 6 months. HCV RNA became undetectable
      during treatment in 46 patients, who then entered the randomized trial. Sustained
      virologic response was observed in 13 of 26 patients who continued ribavirin
      monotherapy and in 15 of 20 patients who stopped use of both IFN and ribavirin
      (P, not significant). Sustained virologic response was significantly more common
      in patients with HCV genotype non-1 (75% vs. 56%) and in patients with a virus
      titer < 2 x 10(6) copies/mL (93% vs. 43%). The results indicate that continuing
      ribavirin monotherapy after achieving a virologic response does not improve
      sustained virologic response.

PMID- 11471098
TI  - Chronic inflammation with increased human immunodeficiency virus (HIV) RNA
      expression in the vaginal epithelium of HIV-infected Thai women.
AB  - Thai residents have a greater risk of heterosexual transmission of human
      immunodeficiency virus (HIV) than do US residents. To analyze host factors
      associated with heterosexual transmission, vaginal epithelial biopsies from HIV
      seropositive Thai and US women were evaluated for tissue virus load and
      histologic makeup. In all, 84% of Thai and 14% of US women exhibited a chronic
      inflammatory T cell infiltrate in the vaginal epithelium. In Thai tissue, the
      infiltrate was associated with elevated levels of HIV RNA in the epidermis.
      Uninfected Thai women also had vaginal epithelial inflammation. Inflammation did
      not correlate with sexually transmitted diseases or HIV disease stage. The higher
      rates and increased risk of heterosexual transmission in Thailand may be due to
      chronic inflammation at the site where the virus is transmitted, which leads to
      the accumulation of activated T cells. Such cells might act as targets for
      initial viral infection and subsequently as reservoirs that support efficient
      transmission.

PMID- 11471099
TI  - The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible
      relevance to human immunodeficiency virus type 1 transmission.
AB  - Topical microbicides are being sought to prevent sexually transmitted diseases by
      inactivating pathogens while preserving or enhancing the natural mucosal barrier.
      Serious public health concerns were raised by a recent phase 3 clinical trial
      that showed that nonoxynol-9 (N-9), a leading microbicide candidate widely used
      as an over-the-counter spermicide, may actually increase human immunodeficiency
      virus type 1 (HIV-1) transmission. The present study links N-9-induced vaginal
      inflammation to increased risk of HIV-1 infection. Analysis of molecular and
      cellular components in cervicovaginal secretions, as well as results from in
      vitro activation of cervicovaginal epithelial cells and U1/HIV promonocytic
      cells, showed that multiple N-9 use can promote HIV-1 transmission through
      interleukin-1-mediated NF-kappaB activation, which leads to chemokine-induced
      recruitment of HIV-1 host cells and increased HIV-1 replication in infected
      cells. Furthermore, this study identifies in vitro and in vivo model systems for
      monitoring undesirable proinflammatory effects of microbicides and other vaginal
      products.

PMID- 11471100
TI  - Two low doses of tenofovir protect newborn macaques against oral simian
      immunodeficiency virus infection.
AB  - Simple affordable interventions are needed to reduce vertical human
      immunodeficiency virus (HIV) transmission in developing countries. The efficacy
      of 2 low doses (4 mg/kg, subcutaneously) or 1 high dose (30 mg/kg,
      subcutaneously) of the reverse-transcriptase inhibitor 9-[2
      (phosphonomethoxy)propyl]adenine (PMPA; tenofovir) to protect newborn macaques
      against simian immunodeficiency virus (SIV) infection was investigated. Thirteen
      newborn macaques were inoculated orally with virulent SIVmac251. The 4 placebo
      treated animals (group A) became persistently infected. Groups B and C (n=4 in
      each group) received 2 4-mg/kg doses of PMPA, either 4 h before and 20 h after
      (group B) or 1 and 25 h after SIV inoculation (group C). One animal (group D)
      received a single 30-mg/kg dose of PMPA 1 h after SIV inoculation. Despite
      evidence of an initial transient infection, 3 group B animals, 2 group C animals,
      and the group D animal were SIV negative and seronegative at ages 19-23 months.
      Immune activation with recall antigens or pharmacologic immunosuppression with
      corticosteroids failed to reactivate viral replication. These data suggest that 1
      or 2 doses of PMPA may protect human newborns against intrapartum HIV infection.

PMID- 11471101
TI  - Urease prevents adherence of Helicobacter pylori to Kato III gastric epithelial
      cells.
AB  - The role of urease in Helicobacter pylori adherence to and internalization by
      Kato III cells was investigated. Kato III cells were incubated with wild-type
      strains (N6 or P1), with isogenic mutants lacking urease (N6ureB::TnKm or
      P1ureA::TnMax5) or producing the inactive apoprotein (N6ureG::TnKm), and with
      urease-positive clones recovered after complementation of N6ureB::TnKm with
      ureAB. Bacteria were stained with the green fluorescent dye PKH2, and the
      bacteria load of cells was analyzed by flow cytometry. With mutants lacking
      urease, the bacteria load was considerably increased, in comparison with the
      corresponding parental strains (P<.001). With clone K2(3), producing larger
      amounts of urease than N6, a significant reduction of bacteria load was observed,
      in comparison with the wild type (P<.001). N6ureG::TnKm showed adherence
      characteristics similar to those of N6. The role of urease in internalization was
      not clear. Thus, urease significantly inhibits H. pylori adherence to Kato III
      cells by a mechanism largely independent of enzymatic activity.

PMID- 11471102
TI  - Vero cytotoxin binding to polymorphonuclear leukocytes among households with
      children with hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in
      childhood, can be caused by different serotypes of vero cytotoxin (VT; i.e.,
      Shiga toxin)-producing Escherichia coli (VTEC). Recently, VT was shown to bind to
      polymorphonuclear leukocytes (PMNL) in the systemic circulation of patients with
      HUS. This study investigated whether VT bound to PMNL could be detected in
      persons in households with patients with HUS. Serum antibodies against E. coli
      O157 and, when available, fecal samples from patients with HUS and household
      members were studied for the presence of VTEC infection. The circulating PMNL of
      82% of the household members were positive for VT, whereas stool and/or serum
      examination showed only 21% positivity. Thus, current methods underestimate the
      number of infected persons in households with patients with HUS.

PMID- 11471103
TI  - Nasopharyngeal carriage of Streptococcus pneumoniae in Finnish children younger
      than 2 years old.
AB  - To describe the natural course of nasopharyngeal carriage of Streptococcus
      pneumoniae and its relationship to acute otitis media (AOM), 329 Finnish children
      were followed from ages 2 to 24 months. In total, 3024 nasopharyngeal (NP) swabs
      (obtained at 10 scheduled healthy visits) and 2007 NP aspirates (obtained during
      respiratory infections) were cultured. Carriage during health increased gradually
      (9%-43%) with age. Within 4 age intervals, carriage was lower during health (13%
      43%) than during respiratory infection without AOM (22%-45%). Higher proportions
      of positive samples were found during AOM (45%-56%), in particular during
      pneumococcal AOM (97%-100%). Antimicrobial treatment reduced carriage only
      temporarily. The most frequent NP serotypes were 6B, 6A, 11, 19F, and 23F. Both
      age and health status were important determinants of NP carriage of S. pneumoniae
      and these features should be considered carefully during analysis of carriage
      rates.

PMID- 11471104
TI  - Invasion of human fallopian tube epithelium by Escherichia coli expressing
      combinations of a gonococcal porin, opacity-associated protein, and chimeric lipo
      oligosaccharide.
AB  - The transepithelial migration of Escherichia coli that expressed all possible
      combinations of a plasmid-encoded gonococcal porin (Por), opacity-associated
      protein (Opa), and 3F11 lipo-oligosaccharide (LOS) epitope was investigated.
      Surface expression of Por mediated selective changes in E. coli antibiotic
      susceptibility, and coexpression of Opa and the 3F11 LOS epitope mediated
      bacterial clumping (P<.01). In the human fallopian tube organ-culture model, Opa
      producing variants attached up to 44-fold better than control bacteria (P<.01),
      and Por-producing variants exceeded submucosal invasion of control bacteria by
      500-fold (P<.01). Opa and Por each facilitated intracellular invasion 20-40-fold
      (P<.01). In dual expresser variants, the 3F11 LOS epitope markedly reduced
      attachment and invasion mediated by Opa or Por. The LOS inhibitory effect was
      curbed when all 3 factors were expressed, which suggests an additional
      interaction of the 3 factors at the bacterial surface. Por, Opa, and LOS play
      important roles in Neisseria gonorrhoeae trafficking across human fallopian tube
      epithelium.

PMID- 11471105
TI  - The dynamics of tuberculosis in response to 10 years of intensive control effort
      in Peru.
AB  - Improved tuberculosis (TB) case detection and cure rates are expected to
      accelerate the decline in incidence of TB and to reduce TB-associated deaths.
      Time series analyses of case reports in Peru showed that the per capita TB
      incidence rate was probably steady before 1991. Case reports increased between
      1990 and 1992 as a result of improved case detection. Although diagnostic efforts
      have continued to increase since 1993, the incidence of new pulmonary TB cases
      has declined in every department of the country, with a national rate of decline
      > or =5.8% per year (range, 1.9%-9.7%). This elevated rate of decline suggests
      that 27% (19%-34%) of cases (158,000) and 70% (63%-77%) of deaths (91,000) among
      smear-positive patients were averted between 1991 and 2000. This is the first
      demonstration that a significant number of TB cases can be prevented through
      intensive short-course chemotherapy in a high-burden country.

PMID- 11471106
TI  - In vivo clearance of glucuronoxylomannan, the major capsular polysaccharide of
      Cryptococcus neoformans: a critical role for tissue macrophages.
AB  - Cryptococcus neoformans produces a life-threatening meningitis in patients who
      are immunocompromised by AIDS. A striking feature of cryptococcosis in AIDS is
      high serum levels of the major capsular polysaccharide, glucuronoxylomannan
      (GXM). Soluble GXM has numerous biologic activities that may contribute to the
      pathogenesis of infection. The objective of the study was to further understand
      in vivo processing of GXM. Mice were injected intravenously with GXM, and the
      tissue distribution was determined. A macrophage suicide technique that used
      liposome-encapsulated dichloromethylene diphosphonate determined the role of
      macrophages. GXM was cleared from serum with a half-life of 24-48 h but was
      retained for an indefinite period in tissues rich in cells of the mononuclear
      phagocyte system. Ablation of macrophages decreased GXM in the liver and spleen
      and increased serum GXM. The results identify a key role for macrophages in the
      clearance of GXM from serum and identify macrophages as a long-term reservoir for
      storage.

PMID- 11471107
TI  - Cellular immune responses of schistosomiasis patients are altered by human
      immunodeficiency virus type 1 coinfection.
AB  - In vitro studies suggest that CD4(+) cells with a T helper 2 (Th2) phenotype
      better support human immunodeficiency virus type 1 (HIV-1) replication than do
      cells of the Th1 phenotype. As a result, Th2-type immune responses may be
      substantially affected by HIV-1 coinfection. To test this hypothesis, a
      comparison was done of proliferation and cytokine production by peripheral blood
      mononuclear cells from patients with schistosomiasis who were positive or
      negative for HIV-1. Patients with schistosomiasis with HIV-1 coinfections had
      significantly lower interleukin (IL)-4 and IL-10 production than did HIV-1
      negative individuals. In contrast, interferon-gamma production levels were
      similar between the 2 groups. Furthermore, in patients with HIV-1, a decrease in
      CD4(+) T cells was correlated with an increased Th1:Th2 cytokine production
      ratio. The effect of praziquantel treatment on proliferation and cytokine
      responses also differed between HIV-1 infection groups. Thus, HIV-1 infection
      affects immune response patterns of patients with schistosomiasis.

PMID- 11471108
TI  - Eliminating onchocerciasis after 14 years of vector control: a proved strategy.
AB  - From 1976 through 1989, weekly aerial spraying operations against blackflies were
      carried out along the rivers of a wide savanna area of West Africa (approximately
      700,000 km(2)) where onchocerciasis was hyperendemic. The level of endemicity
      began to decrease significantly after 4 years of vector control and became very
      low in 1989. This situation has been maintained without any vector control
      activity or chemotherapy, and no incidence of any new cases has been detected. An
      ophthalmological study carried out in 2000 has confirmed these good results,
      showing only cicatricial ocular lesions in the examined population. These results
      led to the conclusion that 14 years of vector control may achieve long-term
      elimination of onchocerciasis, even in the absence of chemotherapy, provided that
      the treated areas are not subjected to any contamination by exogenous parasites
      carried in infected humans or flies.

PMID- 11471109
TI  - Protective immunity to amebiasis: new insights and new challenges.
AB  - Amebiasis, infection with the protozoan parasite Entamoeba histolytica, is the
      third leading cause of death from parasitic diseases. Despite its importance, we
      know little about protective immunity to amebiasis. Now, studies from a cohort of
      children in Bangladesh have provided some critical insights into immunity to
      intestinal amebiasis. Children with mucosal IgA antibodies to the amebic
      adherence lectin were found to be resistant to reinfection with E. histolytica.
      However, immunity was short-lived, and approximately 20% of children in the
      cohort had a second episode of E. histolytica infection during the study period.
      Theses findings indicate that immunity to amebiasis can develop in some children
      after intestinal infection, but protective immunity may be transient, and its
      importance in preventing disease remains to be established.

PMID- 11471110
TI  - Susceptibility of human T cell leukemia virus type 1 to reverse-transcriptase
      inhibitors: evidence for resistance to lamivudine.
AB  - Nucleoside reverse-transcriptase (RT) inhibitors (NRTIs), including lamivudine
      (3TC) and zidovudine (Zdv), are being evaluated for the treatment of human T cell
      lymphotropic virus type 1 (HTLV-1)-associated disease. However, information on
      the susceptibility of HTLV-1 to these drugs is limited. The activity of 5 NRTIs
      on HTLV-1 RT was evaluated. IC(50) values for Zdv, zalcitabine (ddC), didanosine
      (ddI), 3TC, and stavudine (d4T) were determined, using an enzymatic assay, for 5
      HTLV-1 isolates and for reference wild-type and NRTI-resistant human
      immunodeficiency virus type 1 (HIV-1). Both HTLV-1 and wild-type HIV-1 were
      equally susceptible to Zdv, ddC, ddI, and d4T. In contrast, high-level resistance
      to 3TC was found in all HTLV-1 isolates. The findings support the clinical use of
      Zdv, ddC, ddI, and d4T but not of 3TC for the antiretroviral treatment of HTLV-1
      associated disease.

PMID- 11471111
TI  - Relationships among the detection of p24 antigen, human immunodeficiency virus
      (HIV) RNA level, CD4 cell count, and disease progression in HIV-infected
      individuals with hemophilia.
AB  - The aim of this study was to assess the relationships among the detection of p24
      antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and
      disease progression in 111 males with hemophilia who were infected with HIV for <
      or =20 years. Sixty-four individuals (58%) developed p24 antigenemia a median of
      11.6 years after seroconversion. The time to first detection of p24 antigen was
      shorter among those who were older (P=.04) and those with a high initial HIV RNA
      level (P=.006). The median HIV RNA level and CD4 cell count at the time of the
      detection of p24 antigen were 4.95 log(10) copies/mL and 100 cells/mm(3),
      respectively. In univariate analyses, p24 antigenemia was associated with more
      rapid progression to AIDS (relative hazard [RH], 5.50; P=.0001). The effect was
      reduced (RH, 1.85; P=.06) after adjusting for CD4 cell counts and HIV RNA levels
      during follow-up, age, and calendar year. A significant relationship between p24
      antigenemia and death was nonsignificant after adjusting for CD4 cell count.

PMID- 11471112
TI  - Subclinical Legionella infection in workers near the source of a large outbreak
      of Legionnaires disease.
AB  - A survey was conducted of exhibitors at a 1999 floral trade show, where a
      whirlpool spa on display caused a large outbreak of legionnaires disease (LD). In
      total, 742 exhibitors without LD returned a questionnaire on their whereabouts
      during the fair and their health afterward and supplied blood samples for the
      detection of IgM and IgG antibodies against Legionella pneumophila. The
      exhibitors had higher average antibody levels than did the general population.
      The closer to the whirlpool that the exhibitors worked, the higher their antibody
      levels. Both high-normal and high titer levels were found more frequently among
      workers with more exposure, suggesting that serosurveys among potentially exposed
      subjects are a valuable tool for outbreak investigation. Some differences in
      health complaints were observed between the more and less exposed groups, as
      estimated by the workplace location, but few differences were found between
      groups with different antibody levels.

PMID- 11471113
TI  - Osteonecrosis in patients infected with human immunodeficiency virus: a case
      control study.
AB  - To evaluate risk factors for osteonecrosis in human immunodeficiency virus (HIV)
      infected patients, demographic and clinical characteristics of case patients
      (n=17) and control patients (n=34) matched on initial clinic visit date, length
      of follow-up, and baseline CD4 cell count were compared. Case patients were more
      likely to have received corticosteroids (47.1% vs. 8.8%; matched odds ratio [OR],
      13.1; 95% confidence interval [CI], 1.6-106), to have had an increase in CD4 cell
      count from nadir >0.050 x 10(9) cells/L (64.7% vs. 35.3%; OR, 4.9; 95% CI, 1.0
      24), and to have had Pneumocystis carinii pneumonia (52.9% vs. 11.8%; OR, 7.6;
      95% CI, 1.6-36). Use of protease inhibitors and history of other opportunistic
      infections did not significantly differ. In multivariate analysis, use of
      corticosteroids remained significantly associated with osteonecrosis,
      independently of HIV disease stage and protease inhibitor therapy. Corticosteroid
      use is an important risk factor for osteonecrosis, but its pathogenesis is likely
      multifactorial.

PMID- 11471115
TI  - Psychosocial practice trends in pediatric oncology.
AB  - Children with cancer are now living longer lives. As a result, the focus on care
      has shifted to include psychosocial components to help promote healthy adjustment
      to the diagnosis of cancer. In addition, the focus extends to the systems that
      encompass the patient and family. This ranges from cultural needs to comfort care
      and how the medical team and institutions address these issues. Through well
      defined psychosocial practices, children and families are better prepared to cope
      with cancer and become well-adjusted survivors. However, regardless of the
      eventual outcome of the disease, providing psychosocial services can add to the
      quality of life. Many common practices have emerged over the last 25 years, and
      many more will continue to arise as outcome studies continue to address the
      impact of psychosocial services and interventions. This report explores some
      current trends and common psychosocial practices in working with children with
      cancer and their families.

PMID- 11471116
TI  - Pediatric oncology nursing: providing care through decades of change.
AB  - Pediatric oncology nursing practice has evolved over the years as new technology
      and trends in health care have precipitated change. Three pediatric oncology
      nursing leaders share their perspectives on nursing practice as it relates to
      treatment of a child with leukemia during four different points in time. Their
      comments illustrate the challenges, resources, and rewards. Their reflections,
      combined with a survey of the literature over the past half a century, show the
      dramatic impact of advances in supportive care on the practice of caring for a
      child with cancer. It is also evident that as the cure rate has increased, so
      have the efforts to improve quality of life. What has transcended time is the
      delivery of consistent and compassionate care, the education of patients and
      families, and the dedication to advocacy and support.

PMID- 11471117
TI  - From single site to societal belief: the impact of pediatric oncology nursing
      research.
AB  - This review describes the evolution of pediatric oncology nursing research over
      the past 25 years. It highlights practice-changing contributions from single-site
      studies and from multisite trials and discusses strategies for interdisciplinary
      collaboration. Technological advances that will alter the way in which studies
      are conducted and findings are disseminated will influence the future of nursing
      research. Studies implemented by pediatric nurse researchers will continue to
      influence practice and change how we, and others, view the experience of
      childhood cancer.

PMID- 11471118
TI  - Hematopoietic stem cell transplantation: a glimpse of the past and a view of the
      future.
AB  - Hematopoietic stem cell transplantation (HSCT) is still the only definitive
      treatment for some malignant and nonmalignant diseases. The amount of knowledge
      that has been gained regarding this treatment is enormous. Research and
      development has been focused on minimizing transplant-related toxicity and
      disease recurrence. Early experiences of bone marrow administration to patients
      include marrow given by mouth, by intramuscular injection, intramedullary, and by
      intravenous route. Radiation injury in humans was a major stimulus for research
      in bone marrow transplantation. Early research was done on animals and then
      logically applied to humans. Over the last four decades, there was key progress
      made in the development of conditioning regimens, the selection of patients, the
      selection of donors, and prevention and treatment of complications associated
      with the HSCT procedure. It is believed that the recent and future advances of
      HSCT will make the transplant process less complex and more successful. In the
      21st century, there will be marked improvements scientifically, technologically,
      and clinically in the HSCT procedure. If the current rate of research, clinical
      development, and dedication continues, HSCT should be even more rewarding and
      exciting for all clinicians who care for these patients and families.

PMID- 11471119
TI  - APON's first 25 years: a lighter look from the past presidents.
AB  - This report uses an oral history methodology to look back at 25 years of the
      Association of Pediatric Oncology Nurses (APON) from the perspective of the past
      presidents. The different roles and responsibilities of the president and how
      they have evolved over the years are identified. Amusing, behind-the-scenes
      anecdotes from different presidential terms are revealed.

PMID- 11471121
TI  - The ABO blood group gene: a locus of considerable genetic diversity.
AB  - The blood group ABO gene shows considerable polymorphism in most of the 7 exons.
      Introns examined so far have also shown blood group-related polymorphisms, as has
      an upstream enhancer region. Several polymorphisms affect the specificity of the
      gene product (glycosyltransferase) and explain the occurrence of blood group A
      and B. Various lethal mutations result in blood group O. Other mutations are
      presumed to alter the activity rather than the specificity of the enzyme and
      result in weaker A and B blood group phenotypes. In total, 27 A alleles, 15 B
      alleles, 26 O alleles, and 4 AB hybrid alleles are described and surely more will
      surface in the near future. Variation in geographic/ethnic distribution of allele
      frequencies is discussed, along with the confusing nomenclatures currently in
      use.

PMID- 11471122
TI  - Hepatitis G virus biology, epidemiology, and clinical manifestations:
      Implications for blood safety.
AB  - Hepatitis G virus (HGV), also called GBV-C, is a single positive-standard RNA
      virus belonging to the Flaviviridae family. In 50% to 75% of infections, HGV is
      cleared with plasma RNA disappearing as anti-E2 becomes detectable; in other
      cases, HGV infection becomes chronic. The prevalence of HGV RNA in blood donors
      ranges from 1% to 4%, and the rate of anti-E2, indicating resolved infection,
      ranges from 3% to 14%. HGV is transmitted by transfusion of blood components and
      has been transmitted by nonvirally inactivated factor VIII concentrate. Despite
      extensive study, HGV has not been identified as a causative agent of any type of
      liver disease or any other known clinical condition. Molecular biology data show
      a lack of hepatotropism; preliminary data indicate that the site of HGV
      replication may be in mononuclear cells in bone marrow or spleen but not in
      peripheral blood or lymph nodes. The combined clinical and laboratory data
      strongly support the contention that HGV is not a hepatotropic virus and that
      this virus was inappropriately named hepatitis G. Because the data do not
      indicate any pathologic effects of HGV, it is not appropriate to screen the blood
      supply for HGV RNA.

PMID- 11471123
TI  - Managing the anemia of prematurity: red blood cell transfusions versus
      recombinant erythropoietin.
AB  - Transfusion-dependent anemia remains a problem for preterm infants, particularly
      those with a birth weight less than 1.0 kg. Several studies have documented the
      efficacy and safety of transfusing red blood cells stored up to 42 days as a
      means to diminish donor exposures. Recombinant erythropoietin therapy has not
      been widely adopted because it does not consistently reduce the need for red
      blood cell transfusions in very low-birth weight preterm infants.

PMID- 11471124
TI  - Securing viral safety for plasma derivatives.
AB  - The various mechanisms that contribute to the viral safety of therapeutics
      prepared from human blood plasma are examined. The basic principles behind the 2
      most important mechanisms for viral safety, inactivation, and removal are
      discussed, together with the main issues linked to manufacturing. Validation of
      virus safety and protein integrity is considered. Currently available methods for
      inactivation and removal of viruses are reviewed, followed by an overview of new
      and experimental methods that may have some promise for the future. This review
      ends with a brief discussion of the impact fractionation pool size may have on
      product safety and the potential new threat presented by contamination with
      prions.

PMID- 11471125
TI  - Blood donor suitability and allogeneic whole blood donation.
AB  - Blood donor suitability criteria are designed to protect both the blood donor and
      blood recipient from harm. The risks for allogeneic (community) whole blood
      donors who give blood and for blood recipients who receive it are described.
      Blood donor suitability criteria are based on science, informed medical opinion,
      and regulatory rules. The criteria for many common conditions are described.
      Blood donor suitability criteria influence donor demographics and lead to
      specific deferral patterns. Age, gender, and hemoglobin deferral patterns are
      described. Finally, the negative effect of short-term temporary deferrals on
      future blood donations was reviewed.

PMID- 11471127
TI  - Serum leptin levels and anthropometric correlates in Ache Amerindians of eastern
      Paraguay.
AB  - Leptin is a recently discovered peptide hormone secreted primarily from
      adipocytes in humans and other mammals; it is a reflection of fat stores, and has
      been associated with reproductive function. However, few leptin measurements are
      available from nonindustrialized populations, including contemporary
      hunter/gatherer communities undergoing the transition to sedentary agriculture.
      This investigation reports single-sample serum leptin measurements in healthy
      Ache Amerindian males (n = 21; average age, 32.8 +/- 3.4 SE) and females (n = 12;
      average age, 31.3 +/- 4.3) in eastern Paraguay. Ache leptin concentrations were
      much lower than in industrialized populations, although significant sexual
      dimorphism was evident (female 5.64 ng/ml +/- 0.91 SE vs. male 1.13 ng/ml +/-
      0.08; P < 0.0001). Indeed, female leptin levels were similar to those of anorexic
      women, despite apparently adequate adiposity. Controlling for fat percentage, no
      significant sex difference was evident, suggesting that adiposity was the primary
      source of leptin variation. Body fat percentage was highly correlated with leptin
      in females (r2 = 0.72; P < 0.0005) but not males, who exhibited a modest negative
      correlation (r2 = 0.25; P < 0.03). Weight (r2 = 0.45; P = 0.02) and BMI (kg/m2)
      (r2 = 0.81; P < 0.0001) were also significantly correlated in females but not
      males. These results suggest that: 1) clinical leptin norms based on
      industrialized populations may represent the highest range of human variation and
      may not be representative of most human populations; 2) hormonal priming may
      underlie population variation in leptin profiles; and 3) the relative importance
      of leptin as a proximate mechanism regulating reproductive effort during human
      evolution may have been modest.

PMID- 11471128
TI  - Genetic and environmental correlations between various anthropometric and blood
      pressure traits among adult Samoans.
AB  - Shared polygenic effects (i.e., pleiotropy) are assumed to exist for such obesity
      related phenotypes as blood pressure and adiposity. It is possible to identify
      these shared genetic effects through bivariate genetic analyses. This analysis of
      1,342 adult Samoans, across 801 pedigrees, indicates that significant heritable
      components (P < 0.05) ranging from 29-58% exist for weight, height, systolic
      blood pressure, diastolic blood pressure, triceps skinfold, subscapular skinfold,
      body mass index, and sum of skinfolds. In general, the anthropometric
      measurements share additive genetic effects, as do the anthropometric measures,
      with blood pressure. Heritabilities for central fat distribution are not
      significant in this population, which could be due to a lack of power. On the
      other hand, heritabilities have been found in Hispanics; hence the genes
      responsible for central fat distribution may not be evenly distributed among
      populations.

PMID- 11471129
TI  - Secular trend in tooth size in urban Chinese assessed from two-generation family
      data.
AB  - Environmental improvements can lead to greater size of skeletodental structures
      as the population comes closer to expressing its genetic growth potential. Such
      secular trends have been documented in many human settings, especially for
      increased stature and faster tempos of growth. The present study is based on 185
      same-sex parent-offspring pairs of data for maximum buccolingual crown diameters
      of the permanent teeth from a cohort in Beijing, China, where parents experienced
      much of their development during and after World War II with the deprivations of
      the changing regime. Their offspring enjoyed the relative stability of the
      established Communist system, where nutrition and stability were much improved.
      There were significant increases in buccolingual diameters of the premolars and
      molars in the offspring. Increase for premolars and molars was about 1%, but
      larger in females than males (1.6% vs. 0.5%). Opposite changes occurred in the
      incisors and canines (i.e., larger parental dimensions), but we contend that
      these are an age-related artifact brought on by greater passive eruption of older
      individuals' teeth that exposes a broader portion of the crown at the gingival
      margin. The secular trend in crown size coincides with other research in
      contemporary China, disclosing increases in body size and faster tempos of growth
      as health and nutrition continue to improve.

PMID- 11471130
TI  - Mechanical energy oscillations of two brachiation gaits: measurement and
      simulation.
AB  - How do arm-swinging apes locomote effectively over a variety of speeds? One way
      to reduce the metabolic energy cost of locomotion is to transfer energy between
      reversible mechanical modes. In terrestrial animals, at least two transfer
      mechanisms have been identified: 1) a pendulum-like mechanism for walking, with
      exchange between gravitational potential energy and translational kinetic energy,
      and 2) a spring-like mechanism for running, where the elastic strain energy of
      stretched muscle and tendon is largely returned to reaccelerate the animal. At
      slower speeds, a brachiator will always have at least one limb in contact with
      the support, similar to the overlap of foot contact in bipedal walking. At faster
      speeds, brachiators exhibit an aerial phase, similar to that seen in bipedal
      running. Are there two distinct brachiation gaits even though the animal appears
      to simply swing beneath its overhead support? If so, are different exchange
      mechanisms employed? Our kinetic analysis of brachiation in a white-handed gibbon
      (Hylobates lar) indicates that brachiation is indeed comprised of two
      mechanically distinct gaits. At slower speeds in "continuous contact"
      brachiation, the gibbon utilizes a simple pendulum-like transfer of mechanical
      energy within each stride. At faster speeds in "ricochetal" brachiation,
      translational and rotational kinetic energy are exchanged in a novel "whip-like"
      transfer. We propose that brachiators utilize the transfer between translational
      and rotational kinetic energy to control the dynamics of their swing. This
      maneuver may allow muscle action at the shoulder to control the transfer and
      adjust the ballistic portion of the step to meet the requirements for the next
      hand contact.

PMID- 11471131
TI  - Three-dimensional analysis of nonhuman primate trabecular architecture using
      micro-computed tomography.
AB  - Until recently, detailed analyses of the architecture of nonhuman primate
      cancellous bone have not been possible due to a combination of methodological
      constraints, including poor resolution imaging or destructive protocols. The
      development of micro-computed tomography (microCT) and morphometric methods
      associated with this imaging modality offers anthropologists a new means to study
      the comparative architecture of cancellous bone. Specifically, microCT will allow
      anthropologists to investigate the relationship between locomotor behavior and
      trabecular structure. We conducted a preliminary study on the trabecular patterns
      in the proximal humerus and femur of Hylobates lar, Ateles paniscus, Macaca
      mulatta, and Papio anubis to investigate the quantitative differences in their
      trabecular architecture and evaluate the potential of microCT in anthropological
      inquiry. MicroCT allows the researcher to evaluate variables beyond simple two
      dimensional orientations and radiographic densities. For example, this
      methodology facilitates the study of trabecular thickness and bone volume
      fraction using three-dimensional data. Results suggest that density-related
      parameters do not reliably differentiate suspensory-climbing species from
      quadrupedal species. However, preliminary results indicate that measurements of
      the degree of anisotropy, a measure of trabecular orientation uniformity, do
      distinguish suspensory-climbing taxa from more quadrupedal species. The microCT
      method is an advance over conventional radiography and medical CT because it can
      accurately resolve micron-sized struts that make up cancellous bone, and from
      these images a wide array of parameters that have been demonstrated to be related
      to cancellous bone mechanical properties can be measured. Methodological problems
      pertinent to any comparative microCT study of primate trabecular architecture are
      discussed.

PMID- 11471132
TI  - Linking structural variability in long bone diaphyses to habitual behaviors:
      foragers from the southern African Later Stone Age and the Andaman Islands.
AB  - The cross-sectional distribution of cortical bone in long bone diaphyses is
      highly responsive to mechanical loading during life, yet the relationship between
      systemic and localized influences on skeletal structure remains unclear. This
      study investigates postcranial robustness throughout the body among adults from
      two groups of foragers with different patterns and modes of mobility, to
      determine whether there is evidence for upper vs. lower body localization of
      skeletal robustness. The samples used for this comparison are from the southern
      African Later Stone Age (LSA; n = 65, male = 33, female = 28) dating from ca.
      10,000 to 2,000 B.P., and 19th century indigenous Andaman Islanders (AI; n = 36,
      male = 17, female = 16). The LSA were highly mobile foragers who did not exploit
      offshore marine resources. In contrast, the AI had tightly constrained
      terrestrial, but significant marine, mobility. Geometric properties of cortical
      bone distribution in the diaphyses of the clavicle, humerus, femur, tibia, and
      first metatarsal are compared between the samples, providing a representation of
      skeletal robustness throughout the body. Multivariate ANOVA shows the AI to have
      significantly stronger clavicles and humeri, while the LSA femora, tibiae, and
      first metatarsals are stronger than those of the AI. These patterns, in which
      upper and lower limbs show biomechanical properties that are consistent with
      habitual behaviors, suggest localized osteogenic response. Although postcranial
      robustness appears to be correlated with overall limb function, the results
      suggest that more proximal elements within the limb may be more responsive to
      mechanical loading.

PMID- 11471133
TI  - Growth and ontogeny of sexual size dimorphism in the mandrill (Mandrillus
      sphinx).
AB  - We present body mass (N = 419) and crown-rump length (CRL, N = 210) measurements
      from 38 male and 49 female mandrills born into a semifree-ranging colony in order
      to describe growth from birth to adulthood, and to investigate maternal
      influences upon growth. Adult male mandrills are 3.4 times the body mass, and 1.3
      times the CRL, of adult females. Body mass dimorphism arises from a combination
      of sex differences in length of the growth period (females attain adult body mass
      at 7 years, males at 10 years) and growth rate. Both sexes undergo a subadult
      growth spurt in body mass, and this is much more dramatic in males (peak velocity
      551 g/months +/- 89 SEM at 84-96 months). CRL dimorphism arises from bimaturism
      (females attain adult CRL at 6 years, males after 10 years), and neither sex
      shows a particular subadult growth spurt in CRL. Sexual size dimorphism thus
      represents important time and metabolic costs to males, who mature physically
      approximately 3-4 years after females. Considerable interindividual variation
      occurs in the size-for-age of both sexes, which is related to maternal variables.
      Older mothers have heavier offspring than do younger mothers, and higher-ranking
      mothers have heavier offspring than do lower ranking mothers. Mass advantages
      conferred upon offspring during lactation by older and higher-ranking mothers
      tend to persist postweaning in both sexes. Thus maternal factors affect
      reproductive success in both sexes, influencing the age at which offspring mature
      and begin their reproductive career.

PMID- 11471134
TI  - Morphological differences between minicolumns in human and nonhuman primate
      cortex.
AB  - Our study performed a quantitative investigation of minicolumns in the planum
      temporale (PT) of human, chimpanzee, and rhesus monkey brains. This analysis
      distinguished minicolumns in the human cortex from those of the other nonhuman
      primates. Human cell columns are larger, contain more neuropil space, and pack
      more cells into the core area of the column than those of the other primates
      tested. Because the minicolumn is a basic anatomical and functional unit of the
      cortex, this strong evidence showed reorganization in this area of the human
      brain. The relationship between the minicolumn and cortical volume is also
      discussed.

PMID- 11471135
TI  - The Upper Paleolithic triple burial of Dolni Vestonice: pathology and funerary
      behavior.
AB  - This work focuses on paleopathological analysis of one of the skeletons from the
      Gravettian triple burial of Dolni Vestonice (Moravia) and addresses issues of
      Upper Paleolithic funerary behavior. The burial includes the well-preserved
      skeletons of three young individuals. The skeleton in the middle (DV 15) is
      pathological and very problematic to sex; the other two (DV 13 and DV 14) are
      males and lie in an unusual position. The young age, the possibility of a
      simultaneous interment, and the position of the three specimens have given rise
      to speculations about the symbolic significance of this spectacular and
      intriguing funerary pattern. The pathological condition of the skeleton in the
      middle further emphasizes its peculiarity. Main pathological changes of the DV 15
      skeleton include: asymmetric shortening of the right femur and of left forearm
      bones, bowing of the right femur, right humerus, and left radius, elongation of
      fibulae, dysplasias of the vertebral column, and very marked enamel hypoplasias.
      Scrutiny of the medical literature suggests that the most likely etiology is
      chondrodysplasia calcificans punctata (CCP) complicated by trauma and early
      fractures of the upper limbs. CCP is a rare inherited disorder characterized by
      stippled ossification of the epiphyses. The cartilaginous stippling is a
      transient phenomenon that disappears during infancy, leaving permanent
      deformities on affected bones. Among the different forms of CCP, the X-linked
      dominant form is that resulting in asymmetric shortening and is lethal during
      early infancy in males. Thus, survival of DV 15 until young adult age would
      require the specimen to be a female. Clinical findings often associated with the
      disease (erythemas, ichthyosis, alopecia, cataracts, and joint contractures,
      among others) would emphasize the singular aspect of this individual, pointing to
      a condition that should be carefully taken into account when speculating on the
      significance of that peculiar burial.

PMID- 11471136
TI  - Epidemiological approach to the paleopathological diagnosis of leprosy.
AB  - In paleopathology it is usually assumed that modern diagnostic criteria can be
      applied to infectious diseases in the past. However, as both the human species
      and populations of pathogenic microorganisms undergo evolutionary changes, this
      assumption is not always well-founded. To get valid estimates of the frequency
      (the point prevalence at death) of leprosy in skeletal samples, sensitivity,
      specificity, and sample frequency must be estimated simultaneously. It is shown
      that more than three symptoms must be evaluated in at least three samples in
      order to reach estimates with well-described properties. The method is applied to
      three skeletal samples from Medieval Denmark; the samples were scored for the
      presence of seven osteological conditions indicating leprosy. For the
      osteological conditions, sensitivity varied from 0.36-0.80, and specificity from
      0.58-0.98. The frequency of leprosy in the three samples was: Odense (a lepers'
      institution), 0.98, 95% CI 0.64-1.00; Malmo (urban cemetery), 0.02, 95% CI 0.00
      0.07; and Tirup (rural cemetery), 0.36, 95% CI 0.23-0.46. It is concluded that it
      is indeed possible to estimate disease frequencies without reference to modern
      standards, and that leprosy occurred with widely differing frequencies in
      different segments of the Medieval population in southern Scandinavia.

PMID- 11471137
TI  - Developmental and environmental regulation of chloride cells in young American
      shad, Alosa sapidissima.
AB  - Location, abundance, and morphology of gill chloride cells were quantified during
      changes in osmoregulatory physiology accompanying early development in American
      shad, Alosa sapidissima. During the larval-juvenile transition of shad, gill
      chloride cells increased 3.5-fold in abundance coincident with gill formation,
      increased seawater tolerance, and increased Na(+),K(+)-ATPase activity. Chloride
      cells were found on both the primary filament and secondary lamellae in pre
      migratory juveniles. Chloride cells on both the primary filament and secondary
      lamellae increased in abundance (1.5- to 2-fold) and size (2- to 2.5-fold) in
      juveniles held in fresh water from August 31 to December 1 (the period of
      downstream migration) under declining temperature. This proliferation of chloride
      cells was correlated with physiological changes associated with migration
      (decreased hyperosmoregulatory ability and increased gill Na(+),K(+)-ATPase
      activity). Increases in chloride cell size and number of fish in fresh water were
      delayed and of a lower magnitude when shad were maintained at constant
      temperature (24 degrees C). When juveniles were acclimated to seawater, chloride
      cell abundance on the primary filament did not (though size increased 1.5- to 2
      fold), but cells on the secondary lamellae disappeared. Na(+),K(+)-ATPase was
      immunolocalized to chloride cells in both fresh water and seawater acclimated
      fish. The disappearance of chloride cells on the secondary lamellae upon seawater
      acclimation is evidence that their role is confined to fresh water. The
      proliferation of chloride cells in fresh water during the migratory-associated
      loss of hyperosmoregulatory ability is likely to be a compensatory mechanism for
      increasing ion uptake. J. Exp. Zool. 290:73-87, 2001.

PMID- 11471138
TI  - Modulation of prey capture kinematics in the cheeklined wrasse Oxycheilinus
      digrammus (Teleostei: Labridae).
AB  - The ability to modulate prey capture behaviors is of interest to organismal
      biologists as it suggests that predators can perceive features of the prey and
      select suitable behaviors from an available repertoire to successfully capture
      the item. Thus, behavior may be as important a trait as morphology in determining
      an organism's diet. Using high-speed video, we measured prey capture kinematics
      in three cheeklined wrasse, Oxycheilinus digrammus. We studied the effects of
      three experimental prey treatments: live fish, dead prawn suspended in the water
      column, and dead prawn pieces anchored to the substrate in a clip. Live prey
      elicited significantly more rapid strikes than dead prey suspended in the water
      column, and the head of the predator was expanded to significantly larger maxima.
      These changes in prey capture kinematics suggest the generation of more inertial
      suction. With greater expansion of the head, more water can be accelerated into
      the buccal cavity. The attached prey treatment elicited strikes as rapid as those
      on live prey. We suggest that the kinematics of rapid strikes on attached prey
      are indicative of attempts to use suction to detach the prey item. More rapid
      expansion of the buccal or mouth cavity should lead to higher velocities of water
      entering the mouth and therefore to enhanced suction. Further modulation in
      response to the attached prey item, such as clipping or wrenching behaviors, was
      not observed. J. Exp. Zool. 290:88-100, 2001.

PMID- 11471139
TI  - Head shape and bite performance in xenosaurid lizards.
AB  - Bite performance in lizards influences many aspects of the animal's lifestyle.
      During feeding, inter- and intrasexual interactions, and defensive behavior, the
      ability to bite hard might be advantageous. Although biomechanical considerations
      predict clear relations between head shape and bite performance, this has rarely
      been tested. Here we investigate the effect of head shape on bite performance in
      three closely related species of xenosaurid lizards. Our data show that in this
      family of lizards, bite performance is mainly determined by head height, with
      high headed animals biting harder than flat headed ones. Species clearly differ
      in head shape and bite performance and show a marked sexual dimorphism. The
      dimorphism in head shape also results in an intersexual difference in bite
      performance. As head height is the major determinant of bite performance in
      xenosaurid lizards, trade offs between a crevice dwelling life-style and bite
      performance seem to occur. The evolutionary implications of these results are
      discussed. J. Exp. Zool. 290:101-107, 2001.

PMID- 11471140
TI  - Fuel use in hawkmoth (Amphion floridensis) flight muscle: enzyme activities and
      flux rates.
AB  - The fuels used by the hawkmoth Amphion floridensis to power flight are determined
      by nectar-feeding, with fed moths using primarily carbohydrate and unfed moths
      using primarily fat. To investigate the metabolic pathways underlying fuel-use
      flexibility in this species, we measured the maximal activities of several key
      metabolic enzymes in the flight muscle of fed and unfed individuals, for which
      metabolic rates and fuel utilization had been previously determined. Hexokinase
      (HK) and phosphofructokinase (PFK) occur at high activities and, during
      carbohydrate-fueled flight, are estimated to operate at fractional velocities
      comparable to those of exclusively carbohydrate-utilizing insects. Females
      exhibited higher glycolytic enzyme activities than did males, and males regulated
      PFK activity according to nectar feeding. Although beta-hydroxyacyl-CoA
      dehydrogenase (HOAD) was found at high activities, carnitine palmitoyl
      transferase (CPT) was not detectable, suggesting that fatty acids may be utilized
      via a carnitine-independent pathway during flight. Principal component analysis
      revealed a tendency for the activities of citrate synthase, HK, PFK, and HOAD to
      be positively correlated among individuals, as well as a lesser tendency for the
      activities of glycolytic vs. mitochondrial enzymes to be negatively correlated
      with each other. However, the principal components did not correlate with
      variation in either oxygen consumption rate or fuel use in vivo, suggesting that
      variation in enzyme concentration did not determine differences among individuals
      in metabolic performance during flight. J. Exp. Zool. 290:108-114, 2001.

PMID- 11471141
TI  - Thyroxine induces transitions in red muscle kinetics and steady swimming
      kinematics in rainbow trout (Oncorhynchus mykiss).
AB  - During normal development, rainbow trout undergo a shift in red muscle
      contraction kinetics and swimming kinematics. Young trout parr have faster muscle
      kinetics and faster tailbeat frequency during swimming than older, larger
      juvenile trout. In this study, the thyroid hormone thyroxine (T(4)) was used to
      induce these changes in trout parr. This allowed a comparison of swimming
      kinematics, through the use of video analysis and electromyography, and red
      muscle contractile properties, through the use of in vitro muscle preparations,
      between natural parr and same-sized induced juveniles. The red muscle of natural
      parr has faster contractile properties than induced juveniles, including faster
      twitch time and a faster maximum shortening velocity (V(max)). Further, natural
      parr swim with faster tailbeat frequencies than induced juveniles. The results
      suggest that the natural shift in red muscle contraction kinetics observed during
      parr-smolt transfomation in trout directly affects swimming behavior in these
      fish. Also, thyroid hormones appear to induce a shift towards slower isoforms of
      the muscle protein myosin heavy chain (MHC), a result distinct from work on rats
      where thyroid hormones induce shifts towards faster forms of MHC. J. Exp. Zool.
      290:115-124, 2001.

PMID- 11471142
TI  - Mannan-degrading enzymes purified from the crop of the brown garden snail Helix
      aspersa Muller (Gastropoda Pulmonata).
AB  - Two mannan-degrading enzymes were purified from the crop of the terrestrial snail
      Helix aspersa Muller. The crude extracts were taken from dormant (for 4 months)
      snails. The enzymes were a betaD-mannanase of 37.4 +/- 0.3 kDa (EC 3.2.1.78) and
      a betaD-mannosidase of 77.8 +/- 1.9 kDa (EC 3.2.1.25). Both enzymes degraded
      insoluble mannan, releasing either mannose only (beta-mannosidase) or
      oligosaccharides, possibly mannotriose and mannopentaose (beta-mannanase). The
      beta-mannanase had a typical endo-activity pattern, while the beta-mannosidase
      was an exoenzyme. The incubation of both enzymes with mannan increased the
      catalysis by 83%. The best synergy was found with 75% mannosidase combined with
      25% mannanase. The beta-mannanase also hydrolysed beta-linked heteromannans and
      its affinity for different galactomannans was studied. The Km values, varying
      from 2.89 +/- 0.47 mg x ml(-1) to 0.26 +/- 0.01 mg x ml(-1), revealed the
      inhibitory effect of the alphaD-galactosyl residues released. The beta
      mannosidase was acidic (optimum pH = 3.3) and heat-sensitive (50% residual
      activity at 42 degrees C after 5 min of pre-incubation), while the beta-mannanase
      remained stable until 48.5 degrees C (50% residual activity) and over a pH range
      of 4.3-7.5. The properties of these mannanolytic enzymes are discussed in this
      paper compared with those purified in other gastropods and in a bacterium,
      Enterococcus casseliflavus, a quite similar strain previously isolated from this
      snail intestine. The occurrence of thermostable enzymes in H. aspersa digestive
      tract could be a zootechnic parameter of great importance for snail farming. J.
      Exp. Zool. 290:125-135, 2001.

PMID- 11471143
TI  - Differential expression of chicken CYP26 in anterior versus posterior limb bud in
      response to retinoic acid.
AB  - Multiple studies indicate that quantitative control of the levels of all-trans
      retinoic acid (RA) in the vertebrate embryo is necessary for correct development.
      The function of RA in cells is regulated by a number of coordinated mechanisms.
      One of those mechanisms involves controls on the rate of RA catabolism. Recently,
      enzymes capable of catabolizing RA were found to constitute a new family, called
      CYP26, within the cytochrome P450 superfamily. CYP26 homologues have been
      isolated from human, mouse, zebra fish, and recently from the chick. In this
      study, we examined the regulation of chicken CYP26 (cCYP26) expression by RA
      during the early phase of chick limb outgrowth. In the anterior limb mesenchyme
      and apical ectodermal ridge (AER), cCYP26 expression was induced in a
      concentration dependent manner by implanting beads soaked in 0.1, 1, and 5 mg/ml
      RA. The RA-induced expression of cCYP26 in anterior limb mesenchyme and the AER
      was detected as early as 1 hr after treatment and was not affected by the
      presence of cycloheximide. In contrast to the anterior limb, the induction of
      cCYP26 was dramatically reduced (or absent) when RA beads were implanted in the
      posterior limb mesenchyme. Furthermore, induction of cCYP26 expression in the
      anterior mesenchyme was inhibited by transplantations of the zone of polarizing
      activity (ZPA) and by Shh-soaked beads. Our data suggest that different
      mechanisms regulate retinoid homeostasis in the AER and mesenchyme during limb
      bud outgrowth. J. Exp. Zool. 290:136-147, 2001.

PMID- 11471144
TI  - Temporal and quantitative changes in sexual reproductive cycling of the
      cladoceran Daphnia magna by a juvenile hormone analog.
AB  - Cyclic parthenogens, such as the cladoceran, Daphnia magna, utilize both asexual
      (parthenogenetic) and sexual reproduction in order to maximize population fitness
      in variable environments. Parthenogenetic reproduction is the default strategy
      among D. magna, while various environmental cues trigger cycles of sexual
      reproduction. Experiments were conducted with the juvenile hormone analog
      methoprene to test the hypothesis that members of the insect juvenile
      hormone/vertebrate retinoic acid family of transcription factors are involved in
      the regulation of sexual reproduction in daphnids. Neither methoprene, food
      reduction, or crowding independently stimulated entry into the sexual
      reproductive phase of the daphnids. However, the combination of food deprivation
      and crowding stimulated entry into the sexual reproductive phase characterized by
      an initial high production of males and the subsequent intermittent production of
      haploid egg-containing ephippia. Exposure to 160 nM methoprene along with food
      deprivation and crowding caused a significant reduction in the percentage of
      males produced during the early phase of the sexual cycle and significantly
      increased the percentage of males produced during the later stages of the cycle.
      Methoprene concentrations as low as 6.4 nM significantly reduced the number of
      resting eggs produced and proportionately increased the production of
      parthenogenetically-produced neonates. These experiments demonstrate that
      methoprene uncouples the coordinate production of males and resting eggs during
      the sexual reproductive period of D. magna. Methoprene stimulates male offspring
      production and defers their production to latter stages of the sexual
      reproductive period, while inhibiting the production of resting eggs and
      promoting the continuance of parthenogenetic reproduction. J. Exp. Zool. 290:148
      155, 2001.

PMID- 11471145
TI  - Immunocytochemical localization of hydroxyindole-o-methyltransferase (HIOMT) in
      the brain of Myoisophagos lacteus (Nemertea: Heteronemertea: Lineidae).
AB  - In an attempt to identify the brain structures that synthesize melatonin and that
      probably mediate the photoperiodic response of the heteronemertean Myoisophagos
      lacteus, we utilized immunocytochemical techniques and employed immunoglobulins
      directed against hydroxyindole-O-methyltransferase (HIOMT, EC 2.1.1.4). This
      enzyme catalyzes the last step of melatonin biosynthesis. In immunocytochemically
      treated head sections of Myoisophagos lacteus, antibodies labelled a few cells in
      the dorsal region of the dorsal cerebral ganglia. Previous studies have shown
      that melatonin is present both in the brain and eyes of this nemertean species
      and that melatonin is involved in control of the worm reproduction. Other studies
      have demonstrated the presence of photoreceptor-like cells in the same region of
      the worm brain that showed HIOMT immunostaining. Therefore, anatomical findings
      of the present study, coupled with results of previous works, provide strong
      evidence that this region of the worm brain houses a photoperiodic receptor
      involved in melatonin biosynthesis. J. Exp. Zool. 290:156-162, 2001.

PMID- 11471146
TI  - Alterations in habituation of the tail flip response in epigean and troglobitic
      crayfish.
AB  - We demonstrate that the probability of the crayfish, P. clarkii, to tail flip in
      response to a touch on the dorsal tail fan is dependent on both the size and the
      behavioral state of the animal. Alterations in the animal's internal physical
      state, such as when the animal autotomizes its chelipeds, will cause larger-sized
      animals to tail flip; if they were not autotomized, then no tail flip response
      would occur. Altering the external environment by removal of water causes small
      crayfish, which normally habituate slowly, to rapidly habituate. Observation of
      large adult crayfish in a species, O. australis packardi, one that evolved to
      live in total cave darkness, revealed that they are more likely to tail flip than
      are the sighted, adult P. clarkii. Results indicate that the behavioral state of
      the crayfish can result in rapid and long-term alterations in the tail flip
      response and in habituation rates to repetitive stimuli. This ability to show
      plasticity in gain setting may be regulated by neuromodulators and can occur in
      large adults of the sighted crayfish. Differences between the two species
      indicate that size may not be the sole contributing factor to account for tail
      flip behaviors. J. Exp. Zool. 290:163-176, 2001.

PMID- 11471147
TI  - Sex reversal in Nile tilapia (Oreochromis niloticus) using a nonsteroidal
      aromatase inhibitor.
AB  - Several studies have demonstrated that steroid hormones can influence sex
      differentiation in nonmammalian vertebrates and it has been hypothesized that
      male and female sex differentiation are driven by androgen and estrogen hormones,
      respectively. Estrogen biosynthesis is mediated by the steroidogenic enzyme
      cytochrome P450 aromatase, which converts androgens to estrogens. In the present
      study we examined the efficacy of a potent nonsteroidal aromatase inhibitor
      incorporated into the food, on sex reversal of Nile tilapia (Oreochromis
      niloticus) larvae. Nile tilapia larvae were divided in seven groups, which were
      fed with diets containing different amounts of the aromatase inhibitor Fadrozole
      (0, 50, 75 and 100 mg/kg) during 15 and 30 days, starting 9 days after hatching.
      Independent of the period, the proportion of males was significantly higher in
      the treated groups. Treatment with the highest doses (75 and 100 mg/kg) for 30
      days produced 100% males. Histological examination revealed no differences in
      gonadal tissues between control males and treated fish. Furthermore, one intersex
      fish was identified in the group treated with 50 mg Fadrozole/kg for 30 days.
      This study reports that a 100% Nile tilapia male population can be obtained by
      suppressing aromatase activity and suggests that besides steroid hormones,
      nonsteroidal compounds, such as aromatase inhibitors, have potential for
      production of monosex population in tilapia. J. Exp. Zool. 290:177-181, 2001.

PMID- 11471148
TI  - Expression of FTZ-F1alpha in frog testicular cells.
AB  - Fushi tarazu transcription factor-1 (FTZ-F1), a member of a nuclear hormone
      receptor superfamily, is a transcriptional regulator for fushi tarazu gene
      expression in Drosophila (Ueda et al., '90). We have cloned a homologue (rrFTZ
      F1alpha) of the FTZ-F1 gene of the frog Rana rugosa. The gene, in frogs, has been
      shown to have high expression level in the testis (Nakajima et al., 2000). In
      this study, the RT-PCR analysis showed that the FTZ-F1alpha mRNA level in adult
      frogs did not change throughout the year, even during hibernation. However, when
      immunohistological studies using the anti-rrFTZ-F1alpha antibody were employed to
      examine which testicular cells expressed this gene, Sertoli cells were found to
      produce rrFTZ-F1alpha in the two seasons: the breeding season (from March through
      May) and the pre-hibernating season (from October through November). Interstitial
      cells, however, did it in only the breeding season (from April through May).
      Taken together, the results suggest that the rrFTZ-F1alpha expression is
      regulated at the post-transcriptional step, and that the rrFTZ-F1alpha may play
      an important role(s) in the seasonal activities of Sertoli and interstitial cells
      in the frog testis. J. Exp. Zool. 290:182-189, 2001.

PMID- 11471149
TI  - Sexual differentiation in the spiny softshell turtle (Apalone spinifera), a
      species with genetic sex determination.
AB  - It is hypothesized on the basis of sex determination theory that species
      exhibiting genetic sex determination (GSD) may undergo sexual differentiation
      earlier in development than species with environmental sex determination (ESD).
      Most turtle species exhibit a form of ESD known as temperature-dependent sex
      determination (TSD), and in such species the chronology of sex differentiation is
      well studied. Apalone spinifera is a species of softshell turtle (Trionychidae)
      that exhibits GSD. We studied sexual differentiation in this species in order to
      facilitate comparison to TSD species. Eggs were incubated at two different
      temperatures and embryos were harvested at various stages of mid to late
      development. Gonad length was measured with image analysis software, then
      prepared histologically. Indifferent gonads have differentiated in stage 19
      embryos. Histological details of gonadogenesis follow the same pattern as
      described for other reptiles. Regression of the male paramesonephric duct closely
      follows testicular differentiation. Gonad lengths are longer at the warmer
      incubation temperature, and ovaries are generally longer than testes at each
      stage and for each temperature. Although sexual differentiation takes place at
      about the same stage as in other turtles with TSD (18-20), in A. spinifera this
      differentiation is irreversible at this stage, while in some of the TSD species
      sex is reversible until about stage 22. This immutable, definitive sexual
      differentiation may support the hypothesis of an accelerated chronology of sex
      differentiation for this species. We also note that sexual dichromatism at
      hatching is known in this species and may provide additional evidence of early
      differentiation. J. Exp. Zool. 290:190-200, 2001.

PMID- 11471151
TI  - Asymmetry.

PMID- 11471152
TI  - Asymmetry: molecular, biologic, embryopathic, and clinical perspectives.
AB  - This overview of asymmetry addresses the following topics: chiral molecules;
      asymmetric signaling molecules, including N-cadherin, Shh, Fgf8, lefty1, lefty2,
      nodal, Pitx2, activin betaB, activin receptor IIA, and cSnR; situs abnormalities;
      asymmetric cell division; laterality in humans and animals; behavioral asymmetry
      in humans and animals; asymmetric embryopathies, including Tessier-type "clefts";
      hemiasymmetries such as hemihyperplasia, hemihypoplasia, and hemiatrophy;
      asymmetric vascular syndromes, including Klippel-Trenaunay and Sturge-Weber
      syndromes; plagiocephaly of the synostotic and deformational types; somatic
      mosaicism, including a discussion of McCune-Albright syndrome, fibrous dysplasia,
      GNAS1 mutations, and Proteus syndrome.

PMID- 11471153
TI  - Classification of left-right patterning defects in zebrafish, mice, and humans.
AB  - Numerous genes and developmental processes have been implicated in the
      establishment of the vertebrate left-right axis. Although the mechanisms that
      initiate left-right patterning may be distinct in different classes of
      vertebrates, it is clear that the asymmetric gene expression patterns of nodal,
      lefty, and pitx2 in the left lateral plate mesoderm are conserved and that left
      right development of the brain, heart, and gut is tightly linked to the
      development of the embryonic midline. This review categorizes left-right
      patterning defects based on asymmetric gene expression patterns, midline
      phenotypes, and situs phenotypes. In so doing, we hope to provide a framework to
      assess the genetic bases of laterality defects in humans and other vertebrates.

PMID- 11471154
TI  - Role of asymmetric signals in left-right patterning in the mouse.
AB  - Left-right asymmetric signaling molecules in mammals include three transforming
      growth factor beta (TGFbeta)-related factors, Nodal, Lefty1 and Lefty2. They are
      all expressed on the left half of developing mouse embryos. Nodal acts as a left
      side determinant by transducing signals through Smad and FAST and by inducing
      Pitx2 expression on the left side. Lefty proteins are antagonists that inhibit
      Nodal signaling. There are positive and negative transcriptional regulatory loops
      between nodal and lefty2 genes. Thus, Nodal activates its own gene and lefty2.
      Lefty2 protein produced then inhibits Nodal signaling and terminates expression
      of both genes. This feedback mechanism can restrict the range and duration of
      Nodal signaling in developing embryos.

PMID- 11471155
TI  - Organ asymmetries as correlates of other anomalies.
AB  - Fetuses with deviations in the normal left versus right weight relationships of
      the paired viscera were examined for correlation with particular malformations,
      syndromes, or other common factors. Alterations of the normal pattern were
      observed among cases with cytogenetic anomalies, diaphragmatic hernia, renal
      duplication, dyshydramnios, and single umbilical artery. A reversal of the left
      versus right weight pattern was found in the adrenals of cases with hepatic situs
      inversus but not in those with heterotaxic cardiac lesions. Recipient twins in
      the twin-twin transfusion syndrome had reduced left lung weights, presumably
      because of inhibition of lung growth by the enlarged heart. The side of umbilical
      artery absence did not predict either the nature or complexity of associated
      malformations. However, it is suggestive that there is discordance between the
      side of the missing artery and unilateral renal abnormality and that there is
      preferential absence of the right or left artery, depending on the karyotype.

PMID- 11471156
TI  - Disorganization in mice and humans.
AB  - Disorganization (Ds) is an autosomal dominant mouse mutant that produces a
      remarkable array of birth defects. So variable is the phenotype that no two mice
      appear identical. Ds also has markedly reduced penetrance, with 85-99% of Ds mice
      having no apparent anomalies. Paired structures are often affected, but always
      asymmetrically. Although the Ds gene has yet to be identified, it is thought that
      Ds is a gain-of-function mutation, and that Ds malformations are thought to arise
      through a two-hit mechanism. Unlike the two-hit model that has been used to
      describe the development of retinoblastoma, the "second hit" for Ds is thought
      not to arise in the other Ds allele. Although there is a long list of anomalies
      seen in Ds mice, two stand out as most characteristic: hamartomatous skin
      papillae, and mirror-image limb duplications. Through the observation of these
      unusual anomalies in human cases, the possibility of a human homologue of Ds was
      suggested. However, in reviewing types of anomalies seen in Ds mice, it is
      apparent that cases with these unusual defects represent only one end of the
      spectrum of the Ds phenotype. Ds may be the genetic basis for more usual and
      seemingly sporadic human birth defects as well.

PMID- 11471157
TI  - Cilia propel the embryo in the right direction.
AB  - Cilia have long been suspected to play a role in the determination of left-right
      asymmetry. Humans with the dominantly inherited condition Kartagener syndrome
      have defective cilia and a 50% incidence of mirror-image positioning of their
      organs (situs inversus). Analysis of mouse mutations affecting ciliary biogenesis
      and motility has demonstrated that the molecular motors kinesin and dynein are
      required to establish normal handed organismal asymmetry. The cilia that propel
      formation of the embryonic left-right axis are not conventional cilia, but
      monocilia. They are found on the node, or organizer, of the gastrulation-stage
      mouse embryo where they drive net leftward movement of the fluid surrounding the
      node, and initiate left-right asymmetry.

PMID- 11471158
TI  - Clinical aspects of defects in the determination of laterality.
AB  - Of individuals in the human population, 99.99% have developed identical
      thoracoabdominal asymmetry with the cardiac apex, a bilobed lung, the stomach,
      and the spleen on the left side of the midline, and the vena cavae, a trilobed
      lung, the appendix, and the larger liver lobe on the right. This arrangement of
      organs is situs solitus. Occasionally, individuals have a complete, mirror-image
      reversal of this asymmetry called situs inversus, and 20-25% of those individuals
      have an autosomal recessive condition, Kartagener syndrome, with ciliary
      dyskinesia, bronchiectasis, sinusitis, and infertility. Between these extremes of
      situs solitus and situs inversus lies the spectrum of situs ambiguus,
      characterized by isomerism, heterotaxy, and multiple malformations in one or more
      thoracic or abdominal organs. Although most abnormal situs in humans occurs
      sporadically, growing evidence suggests that interference with normal genetic
      mechanisms and pathways may be responsible for most cases. Familial cases suggest
      major effects of both autosomal and X-linked genes with both dominant and
      recessive expression. Situs inversus and situs ambiguus (SI/SA) occurring in
      probands who have close relatives with "isolated," nonsyndromic birth defects
      suggests that some of the pathways important in situs determination may also be
      involved in causing sporadic malformations not obviously associated with a defect
      in laterality determination. Human phenotypes of interest include the association
      of SI/SA with short rib-polydactyly syndromes and renal-hepatic-pancreatic
      dysplasia, and with agnathia and holoprosencephaly. Further elucidation of the
      developmental pathways involved in left-right axis determination should shed
      light on the causes of and relationships among these human phenotypes.

PMID- 11471159
TI  - Genetics of human situs abnormalities.
AB  - Human left-right malformations are usually sporadic, but many familial cases have
      been described. Recognition of these families as well as sporadic cases with
      underlying cytogenetic abnormalities suggest genetic predisposition for many
      instances of situs malformations. Studies in nonhuman vertebrates have led to the
      discovery of several genes conserved in normal left-right development, and
      mutations in some of these have been identified in humans. In addition,
      positional cloning efforts have yielded some success in enlarging our
      understanding of the molecular genetics of human left-right anomalies.

PMID- 11471160
TI  - Comments on biological asymmetry.
AB  - Gross forms of asymmetry of biological structure, hence of development, are
      generally considered abnormalities of conformation with "perfect" symmetry,
      whether bilateral or radial, being regarded as the "ideal" form. This notion,
      primarily a cultural deceit of neo-Platonic origin, can easily be shown to be
      wrong or at best only skin-deep by any student of anatomy or surgery who finds
      the heart not in the midline but, most of the time on the left, liver on the
      right, gut coiled and disposed in a certain direction with appendix in the right
      lower quadrant, and so forth. Indeed, since the beginning of Amphioxus, a major
      effect of evolutionary developmental modification has been the abolition of the
      visceral symmetry which characterized this cephalochordate with introduction of a
      specific pattern of asymmetry called laterality determination. This embryonic
      process, which is beginning to yield its universal molecular basis, is probably
      not responsible for another type of biological phenomenon designated fluctuating
      asymmetry well known to anthropologists (on the basis of quantitative studies of
      morphometric traits of teeth, appendicular skeleton, dermatoglyphics) and well
      known to the ancients who in their most beautiful Hellenistic sculptures
      introduced deliberate asymmetries into facial structure and expression.
      Photographic images constructed of 2 right or 2 left facial halves may differ to
      a starling degree from the authentic face (Fig. 1). The relatively random nature
      of fluctuating asymmetry makes it less likely to be under strong natural
      selection. 1 Middle panel: Frontal view of face of a normal man. Left panel:
      "Artificial" face constructed out of two right halves of the same face. Right
      panel: Face constructed out of two left halves. A careful study of the right and
      left panels makes it easier to appreciate the actual degree of asymmetry present
      in the unaltered middle image/face. However, in addition to laterality
      determination and fluctuating asymmetry, there are additional forms of biological
      asymmetry which have other biological bases such as Lyonization, somatic/clonal
      mosaicism, mosaic aneuploidy/polyploidy, chimaerism, and developmental
      "resistance" seen with especial clarity in virtually every hereditary limb
      malformation. In this paper we will attempt to enumerate the causal forms and
      bases of biological asymmetry.

PMID- 11471161
TI  - Molecular approaches to cerebral laterality: development and neurodegeneration.
AB  - Little is understood about the genetic or epigenetic mechanisms that underlie
      brain asymmetry. Because higher cognitive functions such as language,
      constructional and spatial abilities, and attention are organized along the
      left/right axis, understanding the underpinnings of this process has significant
      implications for both developmental biology and cognitive neuroscience. However,
      scientists have begun to explore, in only the most preliminary manner, the
      influences of subtle biologically inherited brain asymmetries on human behavior
      and disease. Because brain asymmetry develops prenatally, the recognition of
      asymmetry in neurodegeneration implies a possible relationship between the
      development of cerebral laterality and regional vulnerability in
      neurodegenerative diseases. This suggests that the study of cerebral asymmetry
      and laterality is likely to be relevant to a number of degenerative conditions
      that were previously considered to be only diseases of aging. In this article, I
      will outline our perspective and some of the approaches that my laboratory has
      begun to take to characterize the molecular basis of cerebral asymmetry. Most of
      these data are preliminary and the models presented are highly speculative,
      reflecting the primitive stage of work defining the molecular basis of cerebral
      asymmetry.

PMID- 11471162
TI  - Evidence for the "midline" hypothesis in associated defects of laterality
      formation and multiple midline anomalies.
AB  - A male infant was liveborn at 38 weeks of gestation to a G4P1AB2, 22-year-old,
      mother. Polyhydramnios and multiple congenital anomalies were noted by
      ultrasonography; the infant died 5 min after birth. At autopsy, the infant had
      multiple defects of blastogenesis including midline anomalies with asplenia and
      abnormalities of laterality formation. The laterality defects were unusual in
      that they combined asplenia with hypoplastic, symmetrically unilobate lungs and
      bilateral hyparterial bronchi more consistent with polysplenia, abdominal situs
      inversus with midline stomach, symmetric liver, and left gallbladder. No
      intracardiac abnormalities were present, but there was azygous continuation of
      the inferior vena cava. Additional multiple midline defects included
      bronchoesophageal fistula, duodenal atresia, absence of posterior leaf of
      diaphragm; horseshoe adrenal gland; microcephaly; Dandy-Walker anomaly with
      agenesis of cerebellar vermis and occipital encephalocele; holoprosencephaly with
      orbital encephalocele, midline defect of the orbital plate of the skull,
      bilateral anophthalmia, double proboscis with bilateral choanal atresia, midline
      upper lip and palatal cleft; single-lobed thyroid; hypoplastic external genitalia
      with midline cleft of scrotum, long tapering fingers, and defects of the cranium
      at the sites of orbital and occipital encephaloceles. Defects of laterality
      frequently are associated with other complex midline anomalies, which both result
      from a disturbance of pattern formation during blastogenesis, i.e., the induction
      of the progenitor fields. The latter are the result of the establishment of
      upstream expression domains of growth and transcription factors and other
      morphogens. Many of these and other genetic systems, expressed asymmetrically
      around the midline, are responsible for laterality formation and are the result
      of upstream and subsequent downstream gene expression cascades through the
      expression of genes such as HOX genes; bFGF; transforming growth factor
      beta/activins/BMP4; WNT-1,8; and SHH.

PMID- 11471163
TI  - Clinical analysis of families with heart, midline, and laterality defects.
AB  - Disturbances of the normal asymmetric placement of organs, such as polysplenia or
      situs inversus, have been defined traditionally as laterality defects. However,
      there is compelling evidence from vertebrate models and human birth defects to
      hypothesize that defects of the midline, isolated congenital heart defects, and
      laterality defects are etiologically related. We present the clinical
      characteristics of three families that exhibit a variety of midline defects and
      isolated heart defects in addition to laterality defects. These observations
      suggest that the phenotypic consequences of mutations causing laterality defects
      include defects of the midline as well as isolated heart defects. To further
      explore the relationship between midline, heart, and laterality defects, it is
      imperative that detailed phenotyping of individuals and families with laterality
      defects be done and a classification system created to facilitate identification
      of genes causing human laterality disorders.

PMID- 11471164
TI  - SHH mutation is associated with solitary median maxillary central incisor: a
      study of 13 patients and review of the literature.
AB  - Solitary median maxillary central incisor (SMMCI) or single central incisor is a
      rare dental anomaly. It has been reported in holoprosencephaly (HPE) cases with
      severe facial anomalies or as a microform in autosomal dominant HPE (ADHPE). In
      our review of the literature, we note that SMMCI may also occur as an isolated
      finding or in association with other systemic abnormalities. These anomalies
      include short stature, pituitary insufficiency, microcephaly, choanal atresia,
      midnasal stenosis, and congenital nasal pyriform aperture stenosis. SMMCI can
      also be a feature of recognized syndromes or associations or a finding in
      patients with specific chromosomal abnormalities. We performed a molecular study
      on a cohort of 13 SMMCI patients who did not have HPE. We studied two genes,
      Sonic Hedgehog (SHH) and SIX3, in which mutations have been reported in patients
      showing SMMCI as part of the HPE spectrum. A new missense mutation in SHH
      (I111F), segregating in one SMMCI family, was identified. Our results suggest
      that this mutation may be specific for the SMMCI phenotype since it has not been
      found in the HPE population or in normal controls. Published 2001 Wiley-Liss,
      Inc.

PMID- 11471165
TI  - Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients.
AB  - Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis
      characterized by a poikilodermatous rash starting in infancy, small stature,
      skeletal abnormalities, juvenile cataracts, and predisposition to specific
      cancers. We have identified a contemporary cohort of 41 patients to better define
      the clinical profile, diagnostic criteria, and management of patients with RTS.
      Patients with the diagnosis of RTS were ascertained by referrals from
      dermatology, ophthalmology, genetics, and oncology or from direct contact with
      the patient's family. Medical information was obtained from interviews with
      physicians, patients, and their parents and a review of medical records. The age
      range at ascertainment was 9 months to 42 years (28 males and 13 females; M:F,
      2:1). All subjects displayed a characteristic rash. Thirteen subjects had
      osteosarcoma (OS) (32%), eight had radial defects (20%), seven had
      gastrointestinal findings (17%), two had cataracts (6%), and one had skin cancer
      (2%). Twenty-two of 28 patients without OS were less than 15 years old and thus
      remain at significant risk for this tumor. This case-series study reveals a
      clinical profile of RTS that includes a higher prevalence of OS and fewer
      cataracts, compared with historical reports. These differences may reflect either
      allelic or genetic heterogeneity. This study documents the frequency of clinical
      anomalies in a contemporary cohort of RTS patients and revises guidelines for
      diagnosis and management of RTS.

PMID- 11471166
TI  - Incidence of Smith-Lemli-Opitz syndrome in Ontario, Canada.
AB  - Smith-Lemli-Opitz syndrome (OMIM 270400) (SLOS) is caused by inherited enzymatic
      deficiency of 3beta-hydroxysterol-Delta7-reductase (7-dehydrocholesterol-Delta7
      reductase, DHCR7). SLOS is diagnosed clinically by the demonstration of elevated
      levels of 7-dehydrocholesterol (7DHC) in body fluids or tissues. SLOS is
      associated with mental retardation of variable degree and severe behavior
      abnormalities. The physical abnormalities range from minor facial anomalies to
      lethal malformations of the central nervous system, heart, kidneys, and other
      organs. The exact incidence of SLOS is not known. Although there exist estimates
      of the incidence of SLOS ranging from 1 in 20,000 to 1 in 60,000, no prospective
      studies of the incidence of SLOS, based on the clinical data and biochemical
      diagnosis of SLOS, have been performed. Five unrelated cases of SLOS were
      diagnosed in Ontario during a 12-month period. The diagnoses were made based on
      the demonstration of elevated 7DHC in plasma or amniotic fluid. The birth rate
      for Ontario for that period was 132,000 births. The incidence of SLOS in Ontario
      was at least 1 in 26,500 pregnancies in 1999-2000. Given that 86% of the
      population of Ontario is of European origin, the incidence of SLOS in the Ontario
      population of European origin was at least 1 in 22,700. As infants with mild
      forms of SLOS born during this period may remain undiagnosed, these numbers
      likely are underestimates. This observation has implications for prenatal and
      newborn screening for this potentially treatable inherited disorder.

PMID- 11471167
TI  - Analysis of the EPHX1 113 polymorphism and GSTM1 homozygous null polymorphism and
      oral clefting associated with maternal smoking.
AB  - Maternal cigarette smoking during the first trimester of pregnancy is associated
      with an increased risk of having a child with an oral cleft. Compounds present in
      cigarette smoke undergo bioactivation and/or detoxication. Phase I of this
      process results in the formation of reactive epoxides, which can form DNA adducts
      initiating and promoting mutagenesis, carcinogenesis, or teratogenesis.
      Microsomal epoxide hydrolase (mEH; gene symbol EPHX1) catalyzes hydrolysis of
      epoxides. Phase II involves attachment of a moiety (e.g., glutathione) to the
      compound mediated by a variety of enzymes, including glutathione S-transferase,
      generally resulting in a decreased reactivity. Recent studies suggest an
      association between the EPHX1 codon 113 polymorphism or homozygous null GSTM1
      allele and the risk of carcinogenesis, emphysema, phenytoin-associated oral
      clefting, and the risk of spontaneous abortion. This study explores the
      association between EPHX1 codon 113 and homozygous null GSTM1 genotypes and oral
      clefting among infants whose mothers smoked during pregnancy. Case infants were
      diagnosed with isolated cleft lip with or without cleft palate (CL/P). EPHX1
      codon 113 allelotyping was performed on 195 samples (85 cases, 110 controls) by
      PCR/RFLP analysis. 130 samples (79 cases, 51 controls) were tested for the GSTM1
      homozygous null genotype using PCR. Using the odds ratio as a measure of
      association, we did not observe elevated risks of CL/P associated with either
      allelic comparison. This suggests that when mothers smoke periconceptionally,
      their infants having these alleles at either (or both) loci were not at
      substantially increased risk for CL/P compared to infants with the wild-type
      alleles.

PMID- 11471168
TI  - Maternal origin of a unique extra chromosome, der(9)(pter-->q13::q13-->q12:) in a
      girl with typical trisomy 9p syndrome.
AB  - We report on a girl with the typical trisomy 9p syndrome who had an additional E
      sized metacentric chromosome. On the basis of GTG- and CBG-banding, her karyotype
      was considered to be 47,XX,+der(9)(pter-->q13::q13-->q12:) de novo. Results of a
      fluorescence in situ hybridization study using a chromosome 9-specific painting
      probe were compatible with this cytogenetic interpretation. Molecular analyses of
      six highly polymorphic dinucleotide repeat loci on the short arm and the proximal
      long arm of chromosome 9 demonstrated that the girl inherited one allele from her
      father and two identical or different alleles from the mother. We speculated that
      the extra chromosome may have resulted from either nondisjunction of chromosome 9
      followed by a U-type exchange and a crossing-over between different sister
      chromatids during maternal meiosis I and subsequent breakage and malsegregation
      during meiosis II, or nondisjunction during meiosis II followed by isochromosome
      formation in one of the two maternal chromosomes 9 and subsequent breakage.

PMID- 11471169
TI  - Corpus callosum agenesis, multiple cysts, skin defects, and subtle ocular
      abnormalities with a de novo mutation [45,XX,der(5), t(5;;14) (pter;q11.2)].
AB  - We report on a 2-year-old girl with a de novo mutation [45,XX,der(5),t(5;14)
      (pter;q11.2)] with corpus callosum agenesis, multiple cysts (cerebral and
      cardiac), subtle eye abnormalities, and at least two different skin defects,
      strongly indicating neuroectodermal involvement, as a neuromuscular choristoma
      (hamartoma) and an eccrine hamartoma. Fluorescent in situ hybridization with
      different single-locus probes showed that chromosome 5 has a very small deletion,
      confined to a region composed of repetitive sequences. By contrast, the long (q)
      arm of chromosome 14 seems to be much more involved in the rearrangement, with
      partial monosomy spanning from the centromere to the D14S72 and D14S261 loci. The
      extent of the deleted region of chromosome 14 is approximately 16 cM. To our
      knowledge, this is the smallest reported deletion involving the chromosome
      14q11.2 region to be associated with a developmental disorder resulting in
      variable eye, skin, and brain anomalies. We suggest that a new syndrome,
      mimicking in some ways the MLS phenotype, is caused by a deletion in the
      chromosome 14q11.2 region.

PMID- 11471170
TI  - Parental consanguinity in specific types of congenital anomalies.
AB  - Parental consanguinity, as a recognized risk factor for congenital anomalies, has
      mainly been studied with a focus on the types of parental relationships and their
      effects on genetic syndromes or birth defects in general. The present work
      analyzed the association between parental consanguinity and congenital anomalies,
      split, when possible, into clinical subtypes, in an attempt to obtain some
      insight into their recognized etiological heterogeneity. The material consisted
      of 34,102 newborn infants, affected by one of 47 selected congenital anomaly
      types, ascertained by the Latin-American Collaborative Study of Congenital
      Malformations (ECLAMC) during the period from 1967 to 1997. The consanguinity
      rate for each congenital anomaly type was compared with that of the population
      under study (0.96%), and the potentially confounding effect of six selected
      variables was controlled through a conditional logistic regression analysis for
      those congenital anomalies significantly associated with consanguinity. Pre
      occurrence rates for the same congenital anomaly in sibships of consanguineous
      and non-consanguineous cases were compared. A significant association with
      parental consanguinity was observed for three congenital anomaly types:
      hydrocephalus, postaxial hand polydactyly, and bilateral cleft lip +/- cleft
      palate, while three additional anomalies, namely, cephalocele, microcephaly, and
      hand + foot postaxial polydactyly, showed a positive association, but statistical
      significance disappeared after adjustment for confounders, probably owing to
      sample size reduction. The association between consanguinity and Down syndrome
      was mainly due to the confounding effect of maternal age, while for hydrops
      fetalis and 2-3 toe syndactyly, the observed positive association could not be
      tested for confounders due to sample size reduction.

PMID- 11471171
TI  - Third case of cerebral, ocular, dental, auricular, skeletal anomalies (CODAS)
      syndrome, further delineating a new malformation syndrome: first report of an
      affected male and review of literature.
AB  - CODAS syndrome (MIM# 600373) is a rare multiple congenital anomalies syndrome.
      The disorder is highly distinctive with characteristic features consisting of
      developmental delay, cataracts, unusual enamel projections, overfolded and
      crumpled ears, epiphyseal dysplasia, and dysmorphic features (grooved nose,
      ptosis). To date, there have been two affected female children reported. The
      first was a Canadian girl of Mennonite descent, reported by our group, and the
      second was a girl from Brazil. The etiology and pattern of inheritance of CODAS
      is unknown. Herein we report a third affected child, a Canadian male infant of
      Mennonite ancestry. The child, now two years old, exhibits ptosis, cataracts,
      overfolded ears, grooved nasal tip, dental projections, developmental delay, and
      characteristic skeletal anomalies. The findings are characteristic for CODAS
      syndrome. All investigations including karyotype, metabolic screening,
      peroxisomal studies, and studies of cholesterol biosynthesis were normal. The
      underlying defect responsible for CODAS syndrome remains unknown. Many of the
      features suggest a possible underlying collagen gene defect. The fact that this
      child is the second child from the Manitoba Mennonite community, a genetic
      isolate, suggests the possibility of autosomal recessive inheritance. To date,
      there has not been a familial recurrence.

PMID- 11471172
TI  - Variation in genetic and environmental influences in serum lipid and
      apolipoprotein levels across the lifespan in Swedish male and female twins.
AB  - The contribution of genetic and environmental factors to variation in lipids and
      apolipoproteins has been estimated in previous twin and family studies. However,
      it is unclear whether there are sex and/or age differences in parameter
      estimates. We investigated a sample selected from the population-based Swedish
      Twin Registry of 725 like- and unlike-sex twin pairs, ages 17-85. Quantitative
      genetic methods were used to evaluate sex and age differences in genetic and
      environmental variation in lipid and apolipoprotein levels in three age groups,
      17-49, 50-69, and 70-85. Heritabilities for lipids and apolipoproteins ranged
      from 35%-74%. Consistent sex differences were found in triglycerides. Females had
      higher heritabilities (56%) than males (35%) across the age groups. Total
      phenotypic variation increased across the age groups for cholesterol and
      apolipoprotein B due to an increase in unique environmental variance components.
      In contrast, in apolipoprotein A1 variance was highest in the middle age group
      and no differences were found in the phenotypic variance between age groups for
      triglycerides. We concluded that differences in phenotypic variation for
      cholesterol and apolipoprotein B were almost entirely due to the accumulation of
      environmental experiences throughout life, whereas there were no consistent
      patterns of differences in phenotypic variance for apolipoprotein A1 and
      triglycerides.

PMID- 11471173
TI  - Systemic lupus erythematosus in a man with Noonan syndrome.
AB  - Noonan syndrome is a multiple congenital anomaly condition characterized by
      craniofacial anomalies, short stature, cardiac malformations, and normal
      peripheral blood karyotype analysis. Prior reports of individuals with Noonan
      syndrome have revealed an association with several autoimmune diseases, including
      vasculitis and anterior uveitis, but no reports of systemic lupus erythematosus
      (SLE). Here we present the first case report of a 21-year-old man with a clinical
      diagnosis of Noonan syndrome and a recent history of mitral valve dysfunction and
      systemic lupus erythematosus. We discuss his findings in the context of known
      features of Noonan syndrome and propose that individuals with Noonan syndrome be
      regularly monitored for associated autoimmune phenomena.

PMID- 11471174
TI  - Condition of microcephaly, growth retardation, joint contractures, atopic
      dermatitis, and mental retardation in two Japanese sisters: a new autosomal
      recessive MCA/MR syndrome?
AB  - We report on two sisters in a family with a hitherto undescribed MCA/MR condition
      characterized by growth retardation, severe microcephaly, a peculiar facies,
      congenital contractures of the interphalangeal and patellar joints, atopic
      dermatitis, and growth and developmental delay. The disorder in the family we
      describe is similar to but clearly distinguished from tricho-rhino-phalangeal
      syndromes or Bavinck syndrome. We propose that the condition in the sisters
      represents a new autosomal recessive MCA/MR syndrome.

PMID- 11471175
TI  - Silver syndrome is not linked to any of the previously established autosomal
      dominant hereditary spastic paraplegia loci.
AB  - The hereditary spastic paraplegias are a clinically variable and genetically
      heterogeneous group of disorders characterized by progressive and lower limb
      spasticity and weakness. Silver syndrome (SS) is a particularly disabling
      autosomal dominant form of the disease in which there is associated wasting of
      the hand muscles. In view of the fact that genes for hereditary spastic
      paraplegia can produce highly variable phenotypes, the eight known autosomal
      dominant loci were investigated for linkage to Silver syndrome. Genotyping of
      these loci in two large multigenerational families was incompatible with linkage
      to any of these regions, suggesting that an additional locus is responsible for
      this syndrome.

PMID- 11471176
TI  - Ultrasonographic and clinical appearance of a 22-week-old fetus with Brachmann-de
      Lange syndrome.
AB  - The diagnosis Brachmann-de Lange or Cornelia-de Lange syndrome is based on the
      characteristic facial appearance and other malformations. Prenatal
      ultrasonographic diagnosis has been made occasionally usually confirmed by
      clinical photographs of third trimester fetuses with distinctly recognizable hair
      anomalies (synophrys, low anterior and posterior hairlines, and hypertrichosis).
      However, at 22 weeks of gestation, these highly characteristic signs fail to
      support the clinical diagnosis. We report on pre- and post-natal findings in a 22
      week-old female fetus with Brachmann-de Lange syndrome. The facial Gestalt was
      already characteristic and the associated upper limb malformations (bilateral
      monodactyly and ulnar agenesis) supported the diagnosis. The prenatal ultrasound
      images demonstrated a grossly abnormal facial profile (a protruding and
      overhanging upper lip and severe retrognathia) highly suggestive of Brachmann-de
      Lange syndrome. The recurrence risk is estimated &#1%. The recognition of
      Brachmann-de Lange syndrome in second trimester fetuses is essential for genetic
      counselling and reassurance of parents contemplating future reproduction.

PMID- 11471177
TI  - Loss of subtelomeric sequence associated with a terminal inversion duplication of
      the short arm of chromosome 4.
AB  - We report on a 4(1/2)-year-old girl, who presented with multiple minor anomalies
      consistent with trisomy for 4p. GTG-banding identified a de novo terminal
      inversion duplication of distal 4p, dup(4)(p16.3p15.3). Fluorescence in situ
      hybridization (FISH) with a wcp4 probe confirmed the chromosome 4 origin of the
      additional material. FISH with a 4p subtelomere probe, D4F26, showed no signal on
      the dup(4) chromosome identifying a deletion of this region. Molecular analysis
      of 4p STS loci confirmed the subtelomeric deletion and showed loss of the
      paternal allele in this region. The paternal origin of the deleted region and
      homozygosity for one of the two paternal alleles within the region of the
      duplication suggests that a sister chromatid rearrangement on the paternal
      chromosome 4 was involved in the formation of the dup(4) chromosome. To date, the
      best characterized mechanisms of formation of chromosome duplications are
      terminal inversion duplications of 8p, which were shown to be derived from
      rearrangements at maternal meiosis-I. Our data show that mechanisms other than a
      maternal meiosis-I rearrangement can lead to the formation of terminal inversion
      duplications. FISH analysis with the appropriate subtelomeric probes is warranted
      in terminal inversion duplications to check for associated deletions.

PMID- 11471178
TI  - Short stature in a mother and daughter caused by familial der(X)t(X;X)(p22.1
      3;q26).
AB  - Deletions of the terminal Xp regions, including the short-stature homeobox (SHOX)
      gene, were described in families with hereditary Turner syndrome and Leri-Weill
      syndrome. We report on a 10-2/12-year-old girl and her 37-year-old mother with
      short stature and no other phenotypic symptoms. In the daugther, additional
      chromosome material was detected in the pseudoautosomal region of one X
      chromosome (46,X,add(Xp.22.3)) by chromosome banding analysis. The elongation of
      the X chromosome consisted of Giemsa dark and bright bands with a length one
      fifth of the size of Xp. The karyotype of the mother demonstrated chromosome
      mosaicism with three cell lines (46,X,add(X)(p22.3) [89]; 45,X [8]; and
      47,X,add(X)(p22.3), add(X)(p22.3) [2]). In both daughter and mother, fluorescence
      in situ hybridization (FISH), together with data from G banding, identified the
      breakpoints in Xp22.1-3 and Xq26, resulting in a partial trisomy of the terminal
      region of Xq (Xq26-qter) and a monosomy of the pseudoautosomal region (Xp22.3)
      with the SHOX gene and the proximal region Xp22.1-3, including the
      steroidsulfatase gene (STS) and the Kallmann syndrome region. The derivative X
      chromosome was defined as ish.der(X)t(X;X)(p22.1-3;q26)(yWXD2540-, F20cos-, STS-,
      60C10-, 959D10-, 2771+, cos9++). In daughter and mother, the monosomy of region
      Xp22.1-3 is compatible with fertility and does not cause any other somatic
      stigmata of the Turner syndrome or Leri-Weill syndrome, except for short stature
      due to monosomy of the SHOX gene.

PMID- 11471179
TI  - Mosaic inv dup(8p) marker chromosome with stable neocentromere suggests
      neocentromerization is a post-zygotic event.
AB  - Marker chromosomes containing active human neocentromeres have been described in
      individuals where the chromosomes are non-mosaic, suggesting that they are
      mitotically stable, but also in individuals where there is mosaicism, raising the
      possibility of neocentromere instability. We report two independently ascertained
      individuals who are mosaic for a supernumerary marker chromosome, shown by
      reverse chromosome painting to have an 8p origin, resulting in mosaicism for
      tetrasomy 8p23.1-->pter in the patient. The markers have a primary constriction
      but show no detectable centromeric alpha-satellite DNA. The marker in Patient 1
      demonstrated no centromere protein CENP-B binding, but associated with nine
      different functionally critical centromere proteins. Investigation of peripheral
      blood lymphocytes from this patient on five separate occasions over a 13-year
      period showed 23-46% mosaicism for the marker chromosome with no decrease in
      incidence. In vitro investigation of primary and secondary sub-clones of a
      lymphoblast cell line derived from the patient demonstrated 100% stability of the
      marker chromosome indicating that neocentromere instability is unlikely to be
      responsible for the mosaicism in the patient. This and other available data
      support a general model of neocentromerization as a post-zygotic event,
      irrespective of whether the supernumerary chromosome fragment has arisen during
      meiosis or post-fertilization at mitosis.

PMID- 11471180
TI  - Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial
      encoded cytochrome c oxidase subunit II.
AB  - We report the first frame-shift truncation mutation in a mitochondrial DNA
      (mtDNA)-encoded subunit II of cytochrome c oxidase (COXII). The mutation was
      identified by temporal temperature gradient gel electrophoresis (TTGE) followed
      by direct DNA sequencing in an infant who died at 12 days of age following a
      course of apnea, bradycardia, and severe lactic acidosis. The patient had a twin
      brother who died at two days of age of similar course. The mutation, 8042delAT,
      produced a truncated protein that was 72 amino acids shorter than the wild type
      protein. The mutant protein, missing one third of the amino acid residues at the
      C-terminal essential for hydrophilic interaction with cytochrome c, ligand
      binding to CuA and Mg, and the formation of proton and water channels, apparently
      has devastating effects on mitochondrial respiratory function.

PMID- 11471181
TI  - Complex cytogenetic rearrangement of chromosome 8q in a case of Ambras syndrome.
AB  - Ambras syndrome (AMS) is a unique form of congenital universal hypertrichosis.
      The syndrome has been found in association with rearrangements of chromosome 8 in
      two isolated cases. One of these patients was reported to have an apparently
      balanced paracentric inversion of chromosome 8, inv(8)(q12q22). Our cytogenetic
      analysis on this patient showed that the rearrangement of chromosome 8 is more
      complex than initially reported. We detected an insertion of the q23-q24 region
      into a more proximal region of the long arm of chromosome 8 as well as a large
      deletion in 8q23:46,XX, rea(8)(8pter-->8q13::8q23.2-->8q24.1::8q13-
      >8q23.1::8q24.1-->8qter). Given the large number of breakpoints and the presence
      of a substantial deletion, it is surprising that the proposita did not show
      anomalies other than these characteristic of Ambras syndrome.

PMID- 11471182
TI  - Comments on neurofibromatosis 1 and optic pathway tumors.

PMID- 11471183
TI  - Mutation screening in the DHCR7 gene of patients with attention deficit and
      hyperactivity disorder.

PMID- 11471185
TI  - Language -- the barrier and the bridge between science and public.
AB  - What does modern science tell people? That life is ultimately DNA, and DNA is
      genes, and genes are just so many bits of Lego, little building blocks
      manipulated by Nature for 3.8 thousand billion years, rather economically, so
      that much the same genes pop up in a nematode worm, a fruit fly, a lettuce, and a
      thriller writer. And that genes can be transferred from one species, or genus, or
      phylum, or even one kingdom to another. That is why there is unease, and
      newspapers reflect that unease, they do not create it. By helping people confront
      that unease, they probably help people come to terms with it. In the course of
      history, people have felt pretty uneasy about blood transfusion, heart
      transplants, test tube babies, and AIDS, and over the years, have calmed down
      considerably about each, to the advantage of both society and science. It will be
      the same for the human genome project, in a while.

PMID- 11471186
TI  - Can there be a meaningful participation of Croat expatriates in Croatian science?
AB  - The author discusses the possible role for Croat expatriate scientific community
      in Croatian science. He argues that proper leadership could engage Croatian
      expatriate scientific community in supporting the foundation of a
      multidisciplinary science institute in Split, Croatia. The institute could play a
      key role in regional economic development focused on health, energy, and
      environment. Establishment and maintenance of a program of such magnitude
      requires a diminished and more flexible role of the government and introduction
      of the private sector in a government-private partnership. Development of
      necessary attitudes and economic base will take time.

PMID- 11471187
TI  - Protein aggregation and deposition: implications for ion channel formation and
      membrane damage.
AB  - Protein deposition, aggregation, and formation of amyloids are associated with a
      wide range of pathologies, including several neurodegenerative diseases.
      Aggregation and deposition are a result of malfunction in protein folding,
      assembly, and transport, caused by protein mutation and/or changes in the cell
      environment. The mechanism of protein deposition and aggregation is triggered
      when the hydrophobic and positively charged regions of the misfolded proteins are
      exposed. The cells aim to regulate these misfolded and malfunctioning aggregation
      prone proteins by degradation mechanisms, e.g., proteosomes, and/or by storing
      them in specialized compartments, e.g., Russell bodies and aggresomes. During
      these processes, however, some aggregation-prone protein intermediates are
      capable of aggregation and forming beta-sheet based channels in various
      negatively charged cellular membranes. Adverse cellular conditions, transitional
      metals, cellular proteins, and genetic mutations play an important role in the
      formation and function of these non-intrinsic channels. These channels, which can
      damage membrane function, are pathologic because they can disrupt the metabolic,
      ionic, and water homeostasis and distort signal transduction. We propose that
      different conformations of aggregation-prone proteins could alter cell regulation
      by modifying several ion transport systems and also by forming heterogeneous ion
      channels. The changes in membrane transport systems are proposed as early steps
      in impairing neuronal function preceding fibril formation. We conclude that these
      changes damage the membrane by compromising its integrity and increasing its ion
      permeability. This mechanism of membrane damage is a general mechanism that may
      explain other malfunctioning protein processing-related pathologies.

PMID- 11471188
TI  - Structural biology and its applications to the health sciences.
AB  - Part of the decipherment of genomic information lies in understanding the
      structure and function of the protein products of these genes. Protein structure
      is of further importance because of the molecular basis of many diseases.
      Structural biology is the field of research focusing on the experimental
      determination of the structure of biological molecules. We review the field of
      structural biology and its application to medical research and drug discovery,
      and describe the structural results recently obtained in our laboratory for the
      detoxifying enzyme glutathione S-transferase from the Asian mosquito Anopheles
      dirus species B, an important malaria vector. These enzymes have detoxifying
      activity toward pesticides and thus contribute to pesticide resistance in
      insects.

PMID- 11471189
TI  - Inborn errors of metabolism at the turn of the millennium.
AB  - Great progress has been made in the field of hereditary metabolic diseases since
      the beginning of the past century, when metabolic disorders were not really
      understood and could only be clinically described. Due to the development of
      basic sciences and advances in technology, we gained insight in the biochemical
      and molecular basis of hereditary metabolic diseases. It opened possibilities for
      their treatment, and also led to the discovery of more metabolic diseases, so
      today, there are more than 500  inborn errors of metabolism  known. Although each
      of these diseases is quite rare, as a group, however, they affect about 1-2% of
      newborns and therefore pose a significant health problem. The realization about
      50 years ago that some hereditary diseases are curable if timely diagnosed led to
      the introduction of newborn screening in most countries. Modern technologies in
      this field allow early diagnosis of more than 30 inborn errors of metabolism.
      Nevertheless, to diagnose most patients correctly, both selective screening
      involving teamwork and proper use of current technology are required. In addition
      to considerable development of diagnostic possibilities, the past decade was
      marked by advances in the therapy of inborn errors of metabolism. A number of
      clinical trials are currently underway, promising new and more effective
      approaches in the treatment of these patients. Thus, the field of inborn errors
      of metabolism at the beginning of the new millennium continues to be a scientific
      challenge to modern medicine.

PMID- 11471190
TI  - Cellular and molecular interactions between immune system and bone.
AB  - Functional interdependence between immune and bone systems is reflected in a
      number of regulatory molecules acting on the cells of both systems and common
      precursors for bone and immune cells. Therefore, the disturbances of the immune
      system may affect bone metabolism, and vice versa. This review addresses the
      roles of two major immune cell populations, T and B lymphocytes, in the
      regulation of bone metabolism. Experimental models and human diseases
      demonstrated that T lymphocytes may produce many bone cell regulatory cytokines,
      including two essential stimulators of osteoclastogenesis: receptor for
      activation of nuclear factor kappa b (NF-kappa B) (RANK) ligand (RANKL) and
      macrophage colony-stimulating factor. The effect of T lymphocytes on
      osteoclastogenesis may be both stimulatory and inhibitory, and depends on the
      activation stage and pattern of cytokine production. We showed that acute removal
      of T lymphocytes stimulated osteoclast differentiation in vitro and enhanced new
      cartilage and bone formation at non-osseous sites in vivo. B lymphocytes may be
      even more closely related to bone cells, as B lymphopoiesis requires an intimate
      contact with osteoblastic/stromal cells, and estrogens, powerful regulators of
      bone mass, are also involved in the differentiation of the B lymphocyte lineage.
      Also, B lymphocyte progenitors may give rise to functional osteoclasts. Both B
      and T lymphocytes may act through the RANKL/RANK/osteoprotegerin cytokine system,
      which has been independently discovered within immune and bone systems. These
      cytokines have crucial roles in the development and function of osteoclasts,
      dendritic cells, and T and B lymphocytes, as well as in the thymus and lymph node
      organogenesis. The cytokines produced by immune cells may affect bone cell
      function and vice versa, but the full complexity of these interactions awaits
      further investigation.

PMID- 11471191
TI  - Osteogenesis imperfecta at the beginning of bone and joint decade.
AB  - Osteogenesis imperfecta (OI), or brittle bone disease, is a heritable disorder
      characterized by increased bone fragility. Four different types of the disease
      are commonly distinguished, ranging from a mild condition (type I) to a lethal
      one (type II). Types III and IV are the severe forms surviving the neonatal
      period. In most cases, there is a reduction in the production of normal type I
      collagen or the synthesis of abnormal collagen as a result of mutations in the
      type I collagen genes. These classic forms of OI are described in this review.
      There are instances, however, where alterations in bone matrix components, other
      than type I collagen, are the basic abnormalities of the OI. Recently, three such
      discrete types have been identified by histomorphometric evaluation (types V and
      VI) and linkage analysis (Rhizomelic OI). They provide evidence for the as yet
      poorly understood complexity of the phenotype-genotype correlation in OI. We also
      discuss bisphosphonates treatment as well as fracture management and surgical
      correction of deformities observed in the patients with OI. However, ultimately,
      strengthening bone in OI will involve steps to correct the underlying genetic
      mutations that are responsible for this disorder. Thus, we also describe
      different genetic therapeutic approaches that have been tested either on OI cells
      or on available OI murine models.

PMID- 11471192
TI  - Genetic markers of male infertility: Y chromosome microdeletions and cystic
      fibrosis transmembrane conductance gene mutations.
AB  - Today, approximately 15% of couples have reduced fertility. In most cases the
      reason is male infertility, usually of genetic origin. Thus, in the context of
      research in genes involved in reproduction and sex determination, genetic defects
      in gametogenesis are being extensively studied. The most frequent pathogenic
      causes of male infertility are Y chromosomal microdeletions and obstructive
      azoospermia due to congenital absence of the vas deferens (CAVD) in the presence
      of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene. We have investigated the most common CFTR gene alterations in Croatian men
      with CAVD, using Roche research prototype assays. Results revealed that the 5T
      variant was present in 27% of the subjects. The F508 deletion was found in 21% of
      the subjects. It was the most frequent mutation, although its incidence was much
      lower than among patients with cystic fibrosis. The prevalence of microdeletions
      in the azoospermia factor region (AZF) of the Y chromosome in Croatia was 4.5%.
      This is the first report of Y microdeletions in the Croatian population. Genetic
      counseling of all couples with the diagnosis of male infertility is recommended
      before intrauterine insemination, in vitro fertilization, and intracytoplasmic
      sperm injection, and should also include AZF and CFTR genotyping. Couples
      requesting assisted reproductive treatment should be offered molecular analysis
      of the CFTR gene, if male infertility due to obstructive azoospermia is the
      underlying cause. Also, men with severe oligozoospermia or non-obstructive
      azoospermia seeking assisted reproductive treatment should be screened for
      deletions in the Y chromosome.

PMID- 11471193
TI  - Functional genomics of the Down syndrome.
AB  - Down syndrome, as a phenotypic result of trisomy 21, is a complex condition with
      a set of over 30 phenotypic features, which manifest themselves with varying
      frequencies among affected individuals. The importance for molecular medicine of
      understanding the molecular mechanisms underlying Down syndrome becomes fully
      appreciated when a striking feature of Down syndrome is taken into account: that
      the overdose of otherwise perfectly normal genes causes disorders of human
      health, indistinguishable from major public health problems of the general
      population, such as mandatory early onset Alzheimer s degeneration, increased
      risk of leukemia, and protection from cancer of solid tissues. The DNA sequence
      of human chromosome 21 is, at the moment, the most complete piece of DNA sequence
      known in the whole of human genome. The challenge for the future is an
      integrated, multidisciplinary approach to the molecular biology of chromosome 21
      genes, in conjunction with the research into the variation in their genotype,
      expression, and function in the normal population, in Down syndrome individuals
      with well-characterized phenotypic traits, and in euploid patients suffering from
      diseases associated with phenotypic components of Down syndrome: mental
      retardation, developmental defects, hematological and solid tissue malignancies,
      and Alzheimer s disease.

PMID- 11471194
TI  - Engineering dendritic cell grafts for clinical trials in cellular immunotherapy
      of cancer: example of chronic myelogenous leukemia.
AB  - Dendritic cells are pivotal regulators of immune reactivity and immune tolerance.
      The observation that dendritic cells can recruit naive T-cells has invigorated
      cancer immunology and stimulated clinical trials of dendritic cells in
      immunotherapy. However, variables inherent in preparation and use of dendritic
      cell grafts remain to be tested. Here we discuss the role of ex vivo dendritic
      cell processing for in vivo antigen presentation in clinical trials. As an
      example of the complexity in a clinical trial of dendritic cell vaccines, we
      present our ongoing trial in immunotherapy of chronic myelogenous leukemia.

PMID- 11471195
TI  - Dlx5 induces expression of COL1A1 promoter contained in a retrovirus vector.
AB  - AIM: To determine whether retrovirally expressed Dlx5, a homeobox-containing
      transcription factor, can induce a 2.3 kb rat COL1A1 promoter-reporter construct,
      which is transduced into osteoblastic cells by the use of a retrovirus vector.
      METHODS: A self-inactivating retrovirus vector containing the rat COL1A1 driving
      green fluorescent protein (GFP) was transduced into chick calvarial periosteal
      cells. These cells were then infected with a replication-competent retroviral
      vector expressing Dlx5, or a control vector. The cells were cultured in the
      presence of ascorbic acid and beta-glycerol-phosphate, which promotes
      osteoblastic differentiation. Expression of the COL1A1 promoter was assessed by
      detecting GFP with fluorescence microscopy. RESULTS: GFP was detected only in
      cells infected with the Dlx5 expressing retrovirus. The GFP positive cells were
      observed in regions of the culture that had undergone osteoblastic
      differentiation, as detected by cell morphology and the presence of a mineralized
      matrix. CONCLUSION: The 2.3 kb rat COL1A1 promoter fragment contains elements
      responsive to Dlx5, and the self-inactivating retroviral vector allows these
      elements to be used appropriately.

PMID- 11471196
TI  - Maturation of human dendritic cells as sulfasalazine target.
AB  - AIM: Sulfasalazine, a nonsteroidal anti-inflammatory drug, is effective in
      treating some autoimmune diseases, but its mechanism of action is unclear. To
      determine whether dendritic cells could be a possible target of the drug, we
      studied the effects of sulfasalazine and its metabolites, aminosalicylate and
      sulfapyridine, on in vitro maturation (terminal differentiation) of human myeloid
      dendritic cells. METHODS: We prepared immature dendritic cells by incubating CD14
      positive cells in the presence of granulocyte- macrophage colony-stimulating
      factor and interleukin (IL)-4. The cells were matured by addition of tumor
      necrosis factor (TNF)-a, IL-1 beta, and prostaglandin E2 in the presence of
      sulfasalazine or its metabolites -- aminosalicylate and sulfapyridine, or their
      combinations. We quantified the effect of drugs on the dendritic cell
      characteristics, such as stimulation of autologous and allogeneic pan-T cell
      proliferation, surface marker phenotype, IL-12 p40 subunit secretion, and
      activation of nuclear transcription factor (NF)-kappa B. RESULTS: Dendritic cells
      treated with sulfasalazine (1.25 micromol/L or 2.5 micromol/L) could not
      stimulate T cells (p<0.028, two-sided paired t-test). In distinction to drug-free
      maturing dendritic cells, 2.5 micromol/L sulfasalazine upregulated the levels of
      CD14 and CD68 and downregulated the levels of CD40, CD80, and CD83 (for all CD
      markers, p<0.03 for difference between measurements in the absence and the
      presence of sulfasalazine). From concentration-dependent changes in CD83
      expression, we found an apparent ID50 >>1.5 micromol/L sulfasalazine. The
      apparent ID50 value for aminosalicylate-inhibited maturation was 4 micromol/L.
      Sulfapyridine had no effect. At 1.25 micromol/L, sulfasalazine largely inhibited
      NF-kB activation in dendritic cells. CONCLUSION: Maturing human dendritic cells
      are hundred-fold more sensitive to sulfasalazine than T cells and NK cells and
      the most sensitive human cells described so far. Thus, dendritic cell maturation
      is an important target of sulfasalazine. Because of the role of dendritic cells
      in (auto)immunity, inhibition of their maturation might provide a target for
      further optimization of sulfasalazine therapy.

PMID- 11471197
TI  - Liver cell transplantation -- novel animal model for human hepatic viral
      infections.
AB  - AIM: To generate a model of human hepatitis B infection (HBV) in immunocompetent
      rats with chimeric human liver. METHODS AND RESULTS: Normal rats were tolerized
      to human hepatocytes by exposure to human hepatocytes at day 17 of gestation. We
      transplanted human hepatocytes and inoculated HBV into the rats after birth.
      Mixed lymphocytes assay, a measure for tolerance, indicated that animals fetally
      exposed to human hepatocytes developed tolerance to human hepatocytes. Spleen
      lymphocytes from tolerized animals did not proliferate when challenged with donor
      human hepatocytes. In contrast, control animals given saline fetally developed no
      tolerance to human hepatocytes. Tolerant animals with transplanted human
      hepatocytes were susceptible to HBV infection. Western blot analysis and immuno
      histochemistry of liver sections from tolerized, HBV infected animals with
      transplanted human hepatocytes showed the presence of functioning human
      hepatocytes that synthesized human albumin, of which 30% were also positive for
      HB surface antigen and HBV DNA. The presence of covalent closed circular HBV DNA
      in the liver indicated active HBV viral replication. CONCLUSION: Tolerized rats
      with chimeric human livers can be infected with HBV and used as an animal model
      for HBV infection. Tolerized rats with chimeric human livers can also be used for
      generating models of other human hepatic viral diseases.

PMID- 11471198
TI  - Informed consent in genetic research.
AB  - History demonstrates that, without adequate informed consent, research
      participants  rights may be violated and their confidence in research as an
      enterprise undermined. If participants lose confidence in research, they may
      hesitate to participate in future research protocols. Without human participants
      to donate biological samples and participate in protocols, research will be
      difficult, if not impossible to conduct. Thus, appropriate informed consent
      protects both research participants and the enterprise of research itself.
      Informed consent principles in genetics not only help ensure the appropriateness
      of specific research protocols, but they also help support the continuation of
      all types of research on human participants. Most research involving human
      participants raises some issues fundamental to the informed consent process, such
      as whether potential participants truly understand the consequences of their
      participation in a study, and in which circumstances a person is competent to
      give consent. Advances in genetics are raising a new set of informed consent
      issues. The risks that may be involved in genetic research extend far beyond the
      standard considerations of immediate potential harm to study participants.
      Genetic information carries with it the possibility of uncovering a future
      propensity for a given illness. The disclosure of genetic information may lead to
      problems in obtaining health insurance, employment and/or housing discrimination,
      and to social and personal problems not only for participants, but also for their
      family members.

PMID- 11471199
TI  - Predictive genetic testing -- new possibilities in determination of risk of
      complex diseases.
AB  - Predictive genetic testing offers the possibility to statistically determine the
      risk of inheriting a complex phenotype by establishing an individual s genotype
      for metabolic polymorphisms. Here we discuss the conditions under which a
      predictive test may be offered to a patient and the problems connected with it.
      Examples of predictive genetic testing for multifactorial diseases and drug
      responses are given. We describe in detail the association of the C677T
      polymorphism of methylentetrahydrofolate reductase gene with hyperhomocystinemia
      and folate levels, as an independent risk factor for cardiovascular disease, and
      the association of a polymorphism of the promoter of the 5-lipoxygenase gene and
      the response to leukotriene inhibitors in asthma. Prospective development of
      genomic medicine and its use in the study of complex traits will hopefully bring
      significant benefit to the population and enhance the prevention and therapy of
      common diseases.

PMID- 11471200
TI  - Targeted polynucleotides for inhibition of hepatitis B and C viruses.
AB  - AIM: To determine whether a combination of cell targeting and sequence
      recognition of nucleic acids can provide specificity for the inhibition of viral
      gene expression. METHODS: Antisense oligonucleotides complexed to a protein-based
      DNA carrier system were used to target hepatocytes for the inhibition of human
      hepatitis viral gene expression. The DNA carrier system contained an
      asialoglycoprotein as a cell-targeting component, which could direct the uptake
      of complexed DNA specifically to asialoglycoprotein receptors present selectively
      on the surface of mammalian hepatocytes. RESULTS: HBV and HCV viral gene
      expression were substantially and specifically inhibited by use of antisense
      oligonucleotides complexed to a protein-based DNA carrier system. CONCLUSION:
      Targeted delivery of nucleic acids by use of receptor-mediated endocytosis can
      result in inhibition of viral gene expression without host toxicity.

PMID- 11471201
TI  - Oligonucleotide-based gene correction strategies: applications to neuromuscular
      and cardiovascular diseases.
AB  - Gene augmentation is an attractive and viable approach in treatment of inherited
      diseases, despite its limitations, ie, the amount of viral genome in replication
      defective viral vectors is often too small for larger copy DNAs to be inserted.
      In addition, most viral vectors, when assessed in vivo, can elicit a host immune
      response, especially in cases of introduction of a gene copy where protein is
      completely absent, may have potential mutagenic effect on the host genome, or may
      be down-regulated. Therefore, alternative therapeutic approaches are being
      investigated, such as chimeraplasty, in which a mutated allele that already
      exists in an affected individual can be corrected. Although the only gene defects
      that can be corrected by chimeraplasty are point mutations, and the correction
      frequencies are variable, it has been observed that intracellular delivery of
      oligonucleotides is likely to be more efficient than that of plasmid DNA or viral
      vectors, because corrected genes are expressed from their autologous promoters,
      ensuring thus correct spatial and temporal expression, and host immune response
      is not elicited. Another strategy in the therapy of inherited diseases, such as
      Duchenne muscular dystrophy, is the application of antisense RNA
      oligonucleotides, or splicomers, to the exclusion of exons whose mutation leads
      to production of deficient essential proteins. Here we report the recent progress
      made and problems encountered in each of these fields, and discuss the potential
      of nucleotide-based gene correction strategies in treatment of neuromuscular and
      cardiovascular diseases.

PMID- 11471202
TI  - RT-PCR detection of tyrosinase, gp100, MART1/Melan-A, and TRP-2 gene transcripts
      in peripheral blood of melanoma patients.
AB  - AIM: To detect the expression of genes encoding tyrosinase, gp100, MART-1/Melan
      A, and tyrosinase-related protein-2 (TRP-2) in peripheral blood of melanoma
      patients by reverse transcription-polymerase chain reaction (RT-PCR). METHODS:
      Nineteen peripheral blood samples were obtained from 17 melanoma patients. When
      tested, 15 of them presented with clinically detectable metastatic disease.
      Samples of peripheral blood (7 mL) were collected from each patient into
      vacutainer cell preparation tubes. Mononuclear cells were isolated, total
      cellular RNA extracted, and then used as a template for reverse transcription to
      complementary DNA (cDNA). The cDNA was thereafter assayed by PCR for the
      expression of melanocyte-associated transcripts of tyrosinase, gp100, MART1/Melan
      A, and TRP-2 genes. RESULTS: Gp100 gene expression was detected in 13 out of 19
      samples. In 4 of them, TRP-2 gene expression was also detectable. Expression of
      tyrosinase and Melan-A/MART-1 genes could not be observed. Interestingly, gp100
      and TRP-2 gene transcripts were detected in patients having recurrent and/or
      metastatic disease at the time of testing. CONCLUSION: The results we obtained
      support the use of RT-PCR assay for indirect detection of melanoma cells in
      peripheral blood of melanoma patients. As the transcripts for the tyrosinase gene
      and MART-1/Melan A gene were not detected, additional optimization experiments of
      RT-PCR assay are required.

PMID- 11471203
TI  - Gene therapy of brain and endocrine tumors.
AB  - Gene therapy of cancer has become a major interest of medical research since more
      than 60% of the ongoing gene therapy protocols today involve cancer patients. To
      increase the therapeutic index of cancer gene therapy, targeting strategies have
      been developed to ensure that the expression of therapeutic genes is restricted
      exclusively to the tissue of interest. An attractive approach lies in the
      possibility to control the expression of therapeutic genes at the transcriptional
      level by the introduction of tissue-specific or tumor-specific
      enhancers/promoters offers. We have developed transcriptionally targeted vectors
      for gene therapy of solid tumors, including malignant gliomas and epithelial
      thyroid tumors. The choice of these tumor types relies on their clinical impact,
      ie, morbidity and mortality, the lack of effective conventional therapeutic
      strategies, and the ability of these tumors to express tissue/tumor-specific
      genes, whose transcriptional control elements (enhancer/promoter) may be used for
      achieving selective transgene expression. Here we report our clinical and
      preclinical experience in gene therapy of brain and thyroid tumors, and review
      the literature published on this topic.

PMID- 11471204
TI  - Lessons from hereditary pancreatitis.
AB  - For decades there has been slow progress in understanding pancreatic diseases,
      particularly acute and chronic pancreatitis. As a result, there were no
      significant advances in the management of these patients. Treatment was mostly
      directed towards symptomatic relief and management of complications. A simple
      clinical observation that multiple members of a large family are affected by
      acute and chronic pancreatitis, some at very young age and in the absence of any
      alcohol use, led physician-scientists of the Midwest Multicenter Pancreatic Study
      Group (investigators from the University of Cincinnati, University of Kentucky,
      and University of Pittsburgh) to investigate the genetic basis of hereditary
      pancreatitis. Using information from the human genome project, the hereditary
      pancreatitis gene was identified as the cationic trypsinogen gene (protease
      serine 1, PRSS1). This discovery has led to the identification of a number of
      other genes and their products playing role in the pathogenesis of acute and
      chronic pancreatitis. In the emerging picture of pathogenesis of acute and
      chronic pancreatitis, trypsin appears to play a central role. This newly acquired
      knowledge is setting the stage for new preventive and management strategies for
      hereditary and sporadic acute and chronic pancreatitis.

PMID- 11471205
TI  - Prevalence and association of the factor V Leiden and prothrombin G20210A in
      healthy subjects and patients with venous thromboembolism.
AB  - AIM: To determine the prevalences of factor V Leiden and the G20210A mutation in
      the prothrombin gene (PT20210A) and the frequency of their association in healthy
      subjects and in patients with venous thromboembolism (VTE). METHOD: We studied
      160 Croatian patients with at least one episode of VTE and 155 healthy subjects
      as a control group. Genomic DNA was extracted according to standard procedures
      and the presence of factor V Leiden and PT20210A were determined by polymerase
      chain reaction-restriction fragment length polymorphism method. RESULTS: The
      prevalences of factor V Leiden and PT20210A were in VTE patients 21% and 8%
      respectively, and 4% in controls for both mutations. Additionally, 4 patients
      were affected by double heterozygous defects, corresponding to a frequency of 3%,
      whereas none of the controls were double heterozygotes. The coexistence of the
      PT20210A in heterozygous carriers of factor V Leiden was 15% in VTE group. The
      results obtained for different subgroups of VTE patients showed that the carriers
      of analyzed mutations were identified only in subgroups of patients with deep
      venous thrombosis of lower extremities (in 30 patients with factor V Leiden and
      in 13 patients with PT20210A) and superficial venous thrombosis (in 3 patients
      with factor V Leiden). CONCLUSION: The prevalences of factor V Leiden and
      PT20210A in analyzed population of VTE patients are higher than in the group of
      healthy subjects. High frequency of association between both mutations supports
      the need to perform simultaneous genetic analyses of factor V Leiden and PT20210A
      in all VTE patients.

PMID- 11471206
TI  - Physician in war. Dove's Rock.

PMID- 11471207
TI  - [Substance P depresses GABA-activated currents in cultured hippocampal pyramidal
      neurons of rats].
AB  - The purpose of the present study was to explore whether substance P (SP)
      modulates the response mediated by GABAA receptors. Experiments were carried out
      on cultured hippocampal pyramidal neurons of rats. GABA-activated inward currents
      were recorded using the whole-cell-patch-clamp technique. The majority of the
      neurons examined (66/92, 72%) were sensitive to both GABA and SP. When the
      neurons were treated with SP prior to application of GABA, the GABA-activated
      current (IGABA) was inhibited markedly, which was concentration-dependent and
      could be blocked by spantide, an NK1 receptor antagonist. With 10(-8), 10(-7),
      10(-6) and 10(-5) mol/L SP, IGABA was inhibited by 18%, 24.8%, 25.9% and 28%
      respectively. Intracellular application of H7, a potent inhibitor of PKC,
      abolished inhibition of IGABA by SP, suggesting that the inhibition of IGABA by
      SP may be a result of intracellular phosphorylation of the GABAA receptor.

PMID- 11471208
TI  - [Changes in the state of phosphorylation of DARPP-32 of gerbil striatum during
      ischemia].
AB  - Using the mongolian gerbil model of transient forebrain ischemia by bilateral
      carotid arteries occlusion, the levels of phosphorylation and the amount of DARPP
      32 in striatum were measured by back-phosphorylation and Western-blotting assay
      in vitro. Transient forebrain ischemia had no effect on the immunoreaction of
      DARPP-32 in striatum, but the state of phosphorylation of DARPP-32 showed a
      significant change. The [32P] phosphate incorporation in DARPP-32 decreased after
      2, 7 or 10 min of ischemia, but increased after a 5-min ischemia. In contrast,
      the result of back-phosphorylation in vivo was opposite to that obtained in
      vitro.

PMID- 11471209
TI  - [Effect of ATXII on opening modes of myocyte sodium channel, action potential and
      QT intervals of ECG].
AB  - Single sodium channel currents were recorded by patch clamp technique in isolated
      guinea-pig ventricular myocytes, and action potentials of papillary muscle and
      ECG were conventionally measured. Sea anemone toxin (ATXII), a high affinity
      toxin to sodium channel, was used to change the sodium channel dynamics. Changes
      in the duration of action potentials and the QT interval of ECG depending on the
      channel modes were studied in order to provide hints to an understanding of
      pathogenesis of the long QT syndrome (a genetic disease). With the binding of
      ATXII to the sodium channel, the occurrence frequency and the open time constant
      of the "long opening" mode of single Na channels increased significantly, whereas
      the action potential durations, APD50 and APD90, were prolonged by 23% and 27%
      respectively. Following application of ATXII, on the other hand, the QT interval
      and the QTc, a rectified QT interval, increased by 18.6% and 18.9% respectively.
      The results suggest that the dynamics or modes of Na channel play an important
      role in determining the action potential duration and the QT interval of ECG. The
      dynamical changes in Na channels induced by genetic mutation may be partially
      responsible for the long QT syndrome.

PMID- 11471210
TI  - Involvement of pressure-related mechanism in activation of inducible nitric oxide
      synthase.
AB  - The goal of this study was to clarify the relationship between blood pressure and
      inducible nitric oxide synthase (iNOS) activity. Different levels of blood
      pressure were obtained by long-term (six days) intravenous infusion of different
      concentrations (0.3%-8%) of NaCl solution to normal SD rats. iNOS activity assay
      and measurement of urinary nitrate/nitrite (UNOx), an index of NO production of
      the whole body, were carried out by isotope-labeled L-arginine conversion rate
      measurement and Greiss Reaction respectively. Groups of normotensive and
      hypertensive rats including normal Wistar rats, normal Sprague-Dawley (SD) rats,
      high NaCl-induced hypertensive rats (NaHR) and spontaneously hypertensive rats
      (SHR) were used to detect the changes in iNOS protein under normotension and
      hypertension by Western blotting. iNOS activity of aorta and kidney tissues and
      UNOx increased more significantly in hypertensive animals than in the
      normotensive control ones. Accordingly, iNOS protein in the aortas of NaHR and
      SHR increased by 149% and 261% respectively. It is suggested that in addition to
      cytokine and bacterial products etc, blood pressure is also an effective
      regulatory factor involved in iNOS activation and expression.

PMID- 11471211
TI  - [Heat stress-induced HSP70 expression in heart and vessels of simulated
      weightless rats].
AB  - To examine the effect of simulated weightlessness on inducible HSP70 expression
      in the heart and vessel tissues of rats, a tail-suspension rat model was used to
      simulate weightlessness. HSP72 mRNA and HSP70 expression in heart and vessel
      tissues of both simulated weightless and control rats exposed to heat stress
      (ambient temperature, Ta = 43 degrees C) and recovered at Ta of 25 degrees C for
      1 h (CON-H1, SUS-H1) or 2 h (CON-H2, SUS-H2) were analyzed using Northern blot
      and Western blot. The expression of HSP72 mRNA in the myocardium significantly
      decreased in SUS-H2, as compared with that of CON-H2 rats. The amount of HSP72 in
      the myocardium tended to decrease in both SUS-H1 and SUS-H2 groups, as compared
      with the corresponding control groups, but the differences were not statistically
      significant. The levels of inducible HSP70 expression in the vessels were related
      with their anatomical locations, for that the expression of both HSP72 mRNA and
      HSP72 significantly increased in basilar arteries, whereas it showed a slight
      decline in femoral arteries. The blunted HSP70 expression in myocardium suggests
      that simulated weightlessness may induce myocardial changes similar to those in
      aging. However, the HSP70 expression changes in arteries are in accord with the
      trend of differential adaptation changes in vessels to simulated weightlessness.

PMID- 11471212
TI  - [Changes in expression of angiotensin subtype AT1A and AT2 receptors in rats
      during cardiac remodeling following myocardial infarction].
AB  - Immunohistochemical and electron microscopic techniques and image analysis were
      employed to investigate the regulation of cardiac AT1A and AT2 subtype receptors
      in rats during cardiac remodeling following myocardial infarction (MI). Positive
      immunostaining for AT1A and AT2 receptors was observed in myocytes and vessels
      with AT1A being more than AT2. Three days after MI, disappearance of myocardial
      cross striation and fibroblast hyperplasia were found with electron microscopy.
      AT1A receptor protein expression in myocardial noninfarcted portion notably
      increased compared with that in sham-operated control rats (P < 0.001). No
      apparent changes were observed in AT2 receptor (P > 0.05). Two weeks after MI,
      myocyte cross striation and collagen deposition were found. Meanwhile, AT1A
      receptor staining decreased compared with that of three days after MI (P < 0.01),
      but there was still more than that of the control (P < 0.05). AT2 receptor was
      significantly increased compared with that of the sham-operated control rats (P <
      0.001). These results suggest that both AT1A and AT2 receptor protein expression
      was upregulated in noninfarcted myocardium after MI, and the regulation of AT1A
      and AT2 receptors after MI may be involved in post-infarction cardiac remodeling.

PMID- 11471213
TI  - [Action of agmatine on tension of isolated aortic artery and its receptor
      mechanism in rats].
AB  - The effect of agmatine (Agm) on vascular tension and the underlying receptor
      mechanism were investigated in the isolated aortic artery of rats. The results
      are as follows. (1) Agm (10(-7)-10(-2) mol/L) relaxed aortic rings in a
      concentration-dependent manner under the condition of precontraction induced by
      phenylephrine (PE) at a concentration of 10(-6) mol/L. (2) Either in the intact
      or the endothelium-denuded rings, pretreatment with NOS inhibitor NG-nitro-L
      arginine methyl ester (L-NAME, 0.5 mmol/L) did not affect the vascular relaxant
      action of Agm, implying that the concentration-dependent vasorelaxation caused by
      Agm is not endothelium-dependent and NO is not involved. (3) Agm also relaxed
      aortic rings in a concentration-dependent manner under the condition of
      precontraction induced by CaCl2 at a concentration of 3 mmol/L. (4) Idazoxan (10(
      4) mol/L), an alpha 2-adrenergic receptor (alpha 2-AR) and imidazoline receptor
      (IR) antagonist, abolished the Agm-induced vasorelaxation completely under the
      condition of CaCl2-induced precontraction. (5) Yohimbine (10(-4) mol/L), a
      selective alpha 2-AR antagonist, could partially block the vascular relaxant
      action of Agm. It is suggested that the vascular relaxant effect of Agm on the
      rat aortic artery may be mediated by alpha 2-AR and IR.

PMID- 11471214
TI  - [Agmatine inhibits the afferent activity of carotid baroreceptor in rats].
AB  - The effect of agmatine (Agm) on the carotid baroreceptor activity was examined in
      24 anesthetized rats with perfused isolated carotid sinus by recording sinus
      nerve afferent discharges. The results are as follows. (1) By perfusing with 1
      mmol/L Agm, the functional curve for the intrasinus pressure (ISP)-integral of
      sinus nerve activity (ISNA) relation was shifted to the right and downward with
      decreases in peak slope (PS) and peak integral value of carotid sinus afferent
      discharge (PIV). By perfusing with high concentrations of Agm (5 and 10 mmol/L),
      the curves were shifted to the right and downward further with marked decreases
      of PS and PIV. These results showed that Agm exerted an inhibitory action on the
      baroreceptor activity in a dose-dependent manner. (2) The Agm-induced decrease in
      sinus nerve afferent activity was eliminated by pretreatment with IR and alpha 2
      AR blocker idazoxan (0.1 mmol/L). (3) Selective alpha 2-AR blocker yohimbine (15
      mumol/L) partly abolished the inhibitory effect of Agm on baroreceptor. (4)
      Preperfusing with Bay K 8644 (500 nmol/L), an agonist of calcium channels, also
      eliminated the effect of Agm on carotid baroreceptor activity. These results
      indicate that Agm exerts an inhibitory action on carotid baroreceptor and such an
      action may be attributed to the reduction in calcium influx in carotid
      baroreceptor, which is mediated by IR and alpha 2-AR.

PMID- 11471215
TI  - Inhibition of steroidogenesis and induction of apoptosis in rat luteal cells by
      cell-permeable ceramide in vitro.
AB  - The present study was undertaken to investigate the effects of ceramide on
      progesterone production and apoptosis in rat luteal cells in vitro. Luteal cells
      were prepared from the ovaries of pregnant mare serum gonadotropin (PMSG) and
      human chorionic gonadotropin (hCG) primed female Wistar rats and incubated with
      cell permeable C2-ceramide. The effects of ceramide on progesterone production
      and apoptosis in luteal cells were assessed by radio immunoassay (RIA) and flow
      cytometry analysis. In addition, changes in nitric oxide synthase (NOS) activity
      and nitric oxide (NO) production by luteal cells treated with C2-ceramide were
      also evaluated. Ceramide was found to reduce hCG-stimulated progesterone
      production in a dose-dependent manner, whereas it had little effect on basal
      progesterone content. Spontaneous apoptosis in luteal cells was observed after a
      12-hour incubation in vitro and 5 mumol/L of ceramide significantly increased the
      apoptotic rate (P < 0.05). Enhanced apoptotic peak was seen in the histogram by
      flow cytometry. Moreover, 50 mumol/L of C2-ceramide significantly increased NOS
      activity (P < 0.01) and NO production (P < 0.001). It is suggested that ceramide
      may serve as an important signaling molecule mediating certain ovarian processes,
      such as luteal regression.

PMID- 11471216
TI  - [Acetylcholine and A23187 stimulate epinephrine secretion of isolated rat adrenal
      medulla cells in vitro].
AB  - Acetylcholine and A23187, two acetylcholinergic agonists, were used to induce the
      stimulus-secretion coupling of the isolated rat adrenal medulla cells.
      Morphometry of numerical density and electron probe X-ray quantitative
      microanalysis were adopted to measure the alterations in the number and calcium
      content of chromaffin granules in adrenal medulla cells during the agonist
      treatment. Secretion of epinephrine was detected by the high performance liquid
      chromatography (HPLC). It was found that the Ca content of the isolated rat
      adrenal medulla chromaffin granules dropped significantly after a 10-min
      incubation with the agonists, whereas the number of chromaffin granule decreased
      slowly during the agonist treatment and the epinephrine concentration raised
      significantly after a 20-min incubation with the agonists. The decrease of
      granule Ca content occurred earlier than the increase of epinephrine
      concentration, suggesting that the calcium released from chromaffin granule may
      in part account for the induced cell secretion.

PMID- 11471217
TI  - [Selective distribution of IL-1 beta and IL-6 contents in the right and left
      cortices of Balb/c mice].
AB  - The purpose of the present work was to study the different distribution of
      interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) contents in the right and
      left cortices, which may be related to the differences in immunomodulatory
      functions between the two cerebral cortices. Samples of tissue homogenate were
      prepared from the left and right cerebral cortices of the Balb/c mice and IL-1
      beta, and IL-6 contents were measured using ELISA kits. Both IL-1 beta (P < 0.01)
      and IL-6 (P < 0.001) contents of the right cortex were higher than those of the
      left. After injection of LPS, the IL-6 content of the left cortex increased. No
      statistically significant difference of IL-1 beta contents was found between the
      two cerebral cortices, while the IL-6 content of the right cortex was higher than
      that of the left (P < 0.01), suggesting that some cytokines are probably involved
      in the differences between the right and left cerebral immunomodulatory functions
      in mice.

PMID- 11471218
TI  - [Differential expression of genes in the pigeon forebrain after removal of the
      left retina].
AB  - Suppression subtractive hybridization (SSH) was used to analyze differential
      expression of genes in the pigeon forebrain after the left retina of the pigeon
      was removed at hatching. Four genes out of the 14 identified clones produced
      positive hybridization signals as shown by reverse Northern blot. Sequencing
      results showed that the length of PFB/SSH-8 is 226 bp, of which 138 bp produced a
      homology of 85% with human CaMI; the length of PFB/SSH-15 is 252 bp, showing low
      homology with nexin I alpha; no matched homological information was found in the
      remaining 2 clones.

PMID- 11471219
TI  - [Inhibitory effect of aminoglycoside antibiotics on rabbit carotid baroreceptor
      activity in vitro].
AB  - The present study was to investigate the effects of aminoglycoside antibiotics,
      changes in extracellular Ca2+ concentration and antagonists of L-type Ca-channels
      on the activity of rabbit carotid sinus baroreceptors (CS-BRA) in isolated and
      superperfused carotid sinus-carotid sinus nerve (CS-CNS) preparations, using
      extracellular recording technique. The results are as follows. (1) Streptomycin
      (0.25-0.75 mmol/L) and gentamycin (0.43-1.29 mmol/L) inhibited CS-BRA in a dose
      dependent manner, which recovered after the drugs were washed out. (2) Perfusion
      with high Ca2+ (3.3 mmol/L) solution inhibited CS-BRA, while perfusate with trace
      Ca2+ (in the order of 10(-5) mol/L) increased it. (3) Verapamil and diltiazem had
      no effect on CS-BRA at a concentration of 10(-7) mol/L, but inhibited it at
      higher concentrations (> 10(-6) mol/L). These results suggest: (1) aminoglycoside
      antibiotics can inhibit CS-BRA specifically, thus providing a new tool for the
      study of baroreceptors; (2) calcium ions are not necessary for producing
      generator potentials of baroreceptors, and the L-type calcium channel does not
      seem to be involved in CS-BRA per se; and (3) the inhibitory effects of
      aminoglycoside antibiotics on CS-BRA may not be related to the blocking of L-type
      calcium channels.

PMID- 11471220
TI  - [Non-NMDA receptors are involved in the modulation of discharge activity of
      biphasic expiratory neurons and inspiratory neurons].
AB  - Experiments were performed on in vitro brainstem slice preparations from neonatal
      rats that retain respiratory network activity. Extracellular recordings were made
      from 99 neuronal units, respiratory-related or non-respiratory related with
      rhythmical activity, out of which there were 7 biphasic expiratory and 11
      inspiratory ones. Possible roles of non-NMDA receptors in reciprocal excitation
      among the biphasic expiratory neurons and in excitatory synaptic inputs to
      inspiratory neurons were investigated by administration of non-NMDA receptor
      agonist KA and its antagonist DNQX in the perfusion solution. Bath application of
      non-NMDA receptor agonist KA increased the peak frequency of both biphasic
      expiratory and inspiratory neuronal discharges, and increased the discharge
      frequency of the biphasic expiratory neurons and the inspiratory neurons in the
      middle phase, while the frequency of discharge in the early and late phases were
      less affected. All of these effects were blocked by addition of the non-NMDA
      receptor antagonist DNQX, suggesting the involvement of non-NMDA receptors.

PMID- 11471221
TI  - [Correlation between enhanced anoxic tolerance induced by hypoxic preconditioning
      and the stability of mitochondrial membrane potential in cultured hypothalamic
      cells].
AB  - The relationship between enhanced anoxic tolerance induced by hypoxic
      preconditioning and mitochondrial membrane potential (MMP) was studied in
      cultured hypothalamic cells. Dynamic changes in MMP were monitored by confocal
      laser scanning microscopy and expression of B-cell lymphoma/leukemia-2 (bcl-2)
      was examined by flowcytometry. Hypoxic preconditioning increased the cell
      survival rate and decreased the lactate dehydrogenase leakage under acute anoxia,
      in addition to maintaining MMP at a relatively higher level and inducing bcl-2
      overexpression during anoxia. The results suggest that hypoxic preconditioning
      can enhance the tolerance of hypothalamic cells to anoxia, and the underlying
      mechanism may be related to increased stability of MMP. Overexpression of bcl-2
      induced by hypoxic preconditioning may play a role in sustaining the stability of
      MMP.

PMID- 11471222
TI  - [Cholinergic mechanism in the drinking behavior and c-fos expression in brain
      induced by subfornical organ stimulation in rats].
AB  - The drinking behavior and the c-fos expression in rat brain induced by electrical
      stimulation of the subfornical organ (SFO) were examined. SFO stimulation induced
      stable and significant drinking behavior and Fos protein expression in 8 areas of
      the forebrain (organum vasculosum of the lamina terminalis, median preoptic
      nucleus, paraventricular nucleus, supraoptic nucleus, lateral hypothalamic area,
      perifornical dorsal area, substantia innominata and thalamic reunions nucleus),
      and in 3 areas of the hindbrain (area postrema, solitary tract nucleus and
      lateral parabrachial nucleus). In certain neurons of paraventricular and
      supraoptic nuclei, co-expression of Fos protein and vasopressin was induced by
      SFO stimulation. Intracerebroventricular injection of atropine partly blocked the
      SFO stimulation-induced drinking behavior and the Fos protein expression in the
      brain, suggesting that an M-cholinergic mechanism may be involved.

PMID- 11471223
TI  - HLA system. Phenotypic and gene frequencies in celiac and healthy subjects from
      the same geographical area.
AB  - OBJECTIVE: To compare the phenotypic and gene frequencies of the HLA system in
      celiac and healthy subjects the same geographical area. PATIENTS AND METHODS: HLA
      A, B, C, DR and DQ phenotypic and gene frequencies have been estimated in 38
      celiac children and healthy subjects. The HLA typing has been done according to
      the microlymphocytotoxicity assay. The individual HLA antigen frequencies in each
      group have been compared by Chi-square test using Yates correction. For each
      specificity, the strength of association with celiac disease has been estimated
      by Odds Ratio and 95% confidence limit. RESULTS: The comparative study of both
      population show increased phenotypic and gene frequencies among celiac patients
      and significant differences compared with healthy subjects for B8, Cw7, DR3, DR7
      and DQ2. On the contrary, Cw4 and DQ1 phenotypic and gene frequencies are
      significantly increased in the control population. CONCLUSIONS: Our findings
      support the role of HLA antigens as predisposing factors for celiac disease. The
      presence of Cw4 and DQ1 can be a protective factor against such disease.

PMID- 11471224
TI  - Gastro-oesophageal reflux disease: current etiologic, pathogenic and diagnostic
      aspects.

PMID- 11471225
TI  - [Achalasia secondary to radiotherapy in a patient with thymoma and myasthenia
      gravis].

PMID- 11471226
TI  - [Intestinal pseudo-obstruction secondary to hypopotassemia].

PMID- 11471227
TI  - [Abdominal wall hematoma: a complication of paracentesis].

PMID- 11471228
TI  - [Incidence and pathogenesis of acute pancreatitis in Crohn disease].

PMID- 11471229
TI  - [Is dynamic graciloplasty or artificial anal sphincter better in the treatment of
      fecal incontinence? Preliminary study].

PMID- 11471230
TI  - Electrogastrography: the gastric spark.

PMID- 11471231
TI  - Surgical microbiology in risk patients undergoing abdominal surgery.
AB  - INTRODUCTION: Incidence of surgical infection is greater among elderly patients
      undergoing surgery than among the general population, with a serious compromise
      regarding morbidity and mortality in this group of patients with increased risk.
      AIM OF THE STUDY: To determine the microbiological features of surgical
      infections in patients over 65 years of age compared with those younger than 65.
      PATIENTS AND METHODS: Over the past 2 years, 2,064 patients underwent surgery in
      our Department. One thousand three hundred sixty seven of those patients (66.7%)
      had 65 years of age or less and 688 (33.3%) were over 65. Patient characteristics
      regarding the type of surgery (degree of contamination) and the nature and type
      of the condition requiring surgery are reported. One hundred five hundred sixty
      two samples were submitted for microbiological study. The microbiological
      infectious pathogens and their characteristics were determined. The Chi-square
      test was used for the analysis of potential differences related to the age of the
      patient. RESULTS: The rate of samples sent for microbiological study is higher
      among patients over 65. In addition, these patients show both quantitative and
      qualitative differences in their infectious microbiological spectrum, mainly in
      clean-contaminated, contaminated and dirty surgical procedures. Fungal infections
      play a significant role in this group of patients. CONCLUSIONS: Facultative gram
      negative bacilli, aerobic gram-positive cocci, and fungi are the main pathogens
      responsible of surgical infections in elderly patients, compared to all other
      patients, thus requiring specific antibiotic prophylactic and therapeutic
      regimes.

PMID- 11471232
TI  - Reproducibility of ambulatory cutaneous electrogastrography in healthy
      volunteers.
AB  - OBJECTIVE: Cutaneous electrogastrography (cEGG) is a technique used for recording
      gastric electrical activity through electrodes placed on the abdominal skin.
      Given its increasing use for different pathologies, we decided to study its
      reliability (or reproducibility), that had never been appropriately assessed
      before. METHODS: Ambulatory cutaneous electrogastrogram was recorded after US
      location of the gastric antrum in 26 healthy volunteers with ages ranging from 20
      to 60 years. cEGG was recorded during 60 minutes in fasting state and 60 minutes
      after a standard meal and it was repeated in a different day but under the same
      conditions. RESULTS: ANOVA analysis showed significant individual differences
      regarding dominant frequency (DF) (p = 0.19) and power ratio (PR) (p = 0.11), and
      before and after the meal, except for DF (p = 0.12), dominant power (DP) (p =
      0.59) and bradygastria (p = 0.09). No significant differences were found related
      to the day of the recording. The intra-observer agreement index showed a good
      agreement in the DF and the percentage of normogastria (0.91). CONCLUSIONS:
      Currently, DF and normogastria percentage are the most reliable variables for the
      non-invasive study of gastric electric activity.

PMID- 11471233
TI  - Epidemiologic aspects on nonvariceal upper gastrointestinal bleeding in a
      mediterranean region: incidence and sociogeographic and temporal fluctuations.
AB  - AIM: The objectives of this study were to know the incidence of acute nonvariceal
      upper gastrointestinal bleeding (UGIB) in a Mediterranean region, and to analyze
      variations due to sociodemographic (age, gender and Primary Care district) and
      time factors (trend and seasonality). MATERIAL AND METHODS: Longitudinal study
      during 4 years (April 1995 to March 1999) including all cases of nonvariceal UGIB
      admitted to the reference hospital of a Health authority area of the Valencian
      Community, divided into 17 Primary Care districts. Incidence was modeled by
      Poisson regression. RESULTS: Incidence for the whole period was 108 cases per
      100,000 persons-year (95% CI: 100-115). Almost half of the cases (44.9%) were
      associated to the previous use of nonsteroidal anti-inflammatory drugs (NSAIDs).
      Incidence was significantly higher for males and older people. Variations of
      incidence by Primary Care Districts were only significant for NSAID-related UGIB.
      In the time series analysis, we found a negative trend and a clear seasonality
      with higher incidence in autumn and winter compared with spring and summer. When
      relating the seasonality with UGIB, a significant seasonal pattern was only found
      for UGIB caused by duodenal ulcer, and disappeared in subjects with previous use
      of NSAIDs. CONCLUSIONS: In our region, nonvariceal UGIB has a significant
      incidence, but slightly below that reported by other studies carried out in our
      country. The highest incidence of UGIB was observed in males, and increased
      sharply with age. In the time series analysis, a negative trend and a clear
      seasonal pattern that is absent in cases of previous use of NSAIDs, were found.

PMID- 11471234
TI  - A pathway finding system for the cell signaling networks database.
AB  - We report on a knowledge-based pathway-finding system that builds on the cell
      signaling networks database, CSNDB, which we developed previously. This new
      system, PaF-CSNDB, uses a general inference engine to apply rules for finding and
      coupling pathways between or around specific biomolecules from the CSNDB
      database. We show how PaF-CSNDB finds relationships in a large but fragmented
      collection of cell-signaling knowledge by filtering out and composing together
      those sections of pathways specified from an extensive and complex set of binary
      or pair-wise cell-signaling reactions.

PMID- 11471235
TI  - The death factors: a combinatorial analysis.
AB  - This paper presents theoretical and computational tools to understand how a small
      group of proteins, the death factors, are involved in widely different behavior
      of the cell. Experiments were done using a virtual laboratory that can simulate
      cellular response to different external stimuli. WARNING: It is not certain which
      of the theoretical protein clusters described here really occur in nature. In
      addition, the rules of cluster assembly are combinatorial, and thus an
      oversimplification to describe the real situation.

PMID- 11471236
TI  - CoPreTHi: a Web tool which combines transmembrane protein segment prediction
      methods.
AB  - CoPreTHi is a Java based web application, which combines the results of methods
      that predict the location of transmembrane segments in protein sequences into a
      joint prediction histogram. Clearly, the joint prediction algorithm, produces
      superior quality results than individual prediction schemes. The program is
      available at http://o2.db.uoa.gr/CoPreTHi.

PMID- 11471237
TI  - Threading analysis of prospero-type homeodomains.
AB  - The homeodomain is a common structural motif found in many transcription factors
      involved in cell fate determination during development. We have used threading
      analysis techniques to predict whether the atypical homeodomain of prospero
      (pros) family members could form the three-helical homeodomain structural motif,
      even though these proteins are not statistically similar to canonical
      homeodomains as assessed by BLAST searches. Amino acid sequences of these
      divergent homeodomain proteins were threaded through the X-ray coordinates of the
      Drosophila engrailed homeodomain protein [23]. The analysis confirms that the
      prospero class of homeodomain proteins is indeed capable of forming the
      homeodomain structure despite its low degree of sequence identity to the
      canonical homeodomain. Energy calculations indicate that the homeodomain
      structure is stabilized primarily by hydrophobic interactions between residues at
      the helical interfaces. Although the atypical prospero-type homeodomain shows
      very little sequence similarity when compared to other homeodomain proteins, the
      critical amino acids responsible for maintaining the three-dimensional structure
      are highly conserved. A number of other homeodomain proteins, such as PHO2p from
      Saccharomyces and Pax6 from human, were also included in the threading analysis
      and were shown to be able to form the engrailed structure, indicating that there
      are no rigid overall sequence requirements for the formation of the homeodomain
      structural motif. Based on the threading experiments and the subsequent
      structural alignment, a new amino acid signature that unambiguously identifies
      the prospero-type proteins was deduced.

PMID- 11471238
TI  - SEView: a Java applet for browsing molecular sequence data.
AB  - SEView is a Java applet that represents known or predicted elements of a protein
      or nucleotide sequence. It replaces or supplements the textual format of
      databases or program output with an interactive, graphical representation that is
      easily available through a WWW browser. Independence from the source data's
      format is achieved through a description language and ad hoc translators, which
      make the system versatile and flexible.

PMID- 11471239
TI  - Evaluation of computer tools for the prediction of transcription factor binding
      sites on genomic DNA.

PMID- 11471240
TI  - Muscle actin genes: a first step towards computational classification of tissue
      specific promoters.
AB  - Tissue-specific gene expression is governed by enhancer and promoter sequences
      determining the specificity most probably by their internal organization of
      transcription factor binding sites. In case of muscle-specific gene expression
      excellent compilations of sequence regions responsible for the tissue-specificity
      are available. We took advantage of such a compilation in order to elucidate
      organizational features that are directly correlated with promoter specificity.
      We chose a systematic approach solely based on a sequence collection known to
      consist of specific regulatory regions which can in principle be applied to every
      precompiled set of such sequences. We were able to show that these sequences
      contained a detectable subgroup (actin promoters) for which it was possible to
      construct a highly specific promoter model recognizing the majority of all known
      actin sequences. The model was robust with respect to different training sets,
      almost 100% specific and sensitive enough to be suitable for database searches.
      We believe this pilot study demonstrates the general applicability of our
      approach as well as the concept of modular promoter organization.

PMID- 11471241
TI  - Quantitative modeling of biochemical networks.
AB  - Today different database systems for molecular structures (genes and proteins)
      and metabolic pathways are available. All these systems are characterized by the
      static data representation. For progress in biotechnology the dynamic
      representation of this data is important. The metabolism can be characterized as
      a complex biochemical network. Different models for the quantitative simulation
      of biochemical networks are discussed, but no useful formalization is available.
      This paper shows that the theory of Petrinets is useful for the quantitative
      modeling of biochemical networks.

PMID- 11471242
TI  - Homology model building of Hho1p supports its role as a yeast histone H1 protein.
AB  - Biochemical studies to date have not been able to identify the linker histone H1
      protein in the budding yeast Saccharomyces cerevisiae. Database homology
      searching against the complete yeast genome has identified a gene, HHO1, (or
      YPL127C, formerly LPI17) which encodes a protein that has two regions that show
      similarity to the pea histone H1 globular domain. To determine whether Hho1p can
      assume the shape of an H1 protein, homology model building experiments were
      performed using the structure of chicken histone H5 globular domain as the basis
      for comparison. A statistically significant match between each of the two
      globular domains of Hho1p and the chicken histone H5 structure was obtained, and
      probability values indicate that there is a less than 1 in 100 chance that such a
      match would be the result of a random event. These findings support the proposal
      that Hho1p acts as an "H1 dimer" and could be responsible for the decreased
      linker DNA length observed between nucleosomal core particles.

PMID- 11471243
TI  - Sources of systematic error in functional annotation of genomes: domain
      rearrangement, non-orthologous gene displacement and operon disruption.
AB  - Functional annotation of proteins encoded in newly sequenced genomes can be
      expected to meet two conflicting objectives: (i) provide as much information as
      possible, and (ii) avoid erroneous functional assignments and over-predictions.
      The continuing exponential growth of the number of sequenced genomes makes the
      quality of sequence annotation a critical factor in the efforts to utilize this
      new information. When dubious functional assignments are used as a basis for
      subsequent predictions, they tend to proliferate, leading to "database
      explosion". It is therefore important to identify the common factors that hamper
      functional annotation. As a first step towards that goal, we have compared the
      annotations of the Mycoplasma genitalium and Methanococcus jannaschii genomes
      produced in several independent studies. The most common causes of questionable
      predictions appear to be: i) non-critical use of annotations from existing
      database entries; ii) taking into account only the annotation of the best
      database hit; iii) insufficient masking of low complexity regions (e.g. non
      globular domains) in protein sequences, resulting in spurious database hits
      obscuring relevant ones; iv) ignoring multi-domain organization of the query
      proteins and/or the database hits; v) non-critical functional inferences on the
      basis of the functions of neighboring genes in an operon; vi) non-orthologous
      gene displacement, i.e. involvement of structurally unrelated proteins in the
      same function. These observations suggest that case by case validation of
      functional annotation by expert biologists remains crucial for productive genome
      analysis.

PMID- 11471244
TI  - A neural network model approach to the study of human TAP transporter.
AB  - We used an artificial neural network (ANN) computer model to study peptide
      binding to the human transporter associated with antigen processing (TAP). After
      validation, an ANN model of TAP-peptide binding was used to mine a database of
      HLA-binding peptides to elucidate patterns of TAP binding. The affinity of HLA
      binding peptides for TAP was found to differ according to the HLA supertype
      concerned: HLA-B27, -A3 or -A24 binding peptides had high, whereas HLA-A2, -B7 or
      -B8 binding peptides had low affinity for TAP. These results support the idea
      that TAP and particular HLA molecules may have co-evolved for efficient peptide
      processing and presentation. The strong similarity between the sets of peptides
      bound by TAP or HLA-B27 suggests functional co-evolution whereas the lack of a
      relationship between the sets of peptides bound by TAP or HLA-A2 is against these
      particular molecules having co-evolved. In support of these conclusions, the
      affinities of HLA-A2 and HLA-B7 binding peptides for TAP show similar
      distributions to that of randomly generated peptides. On the basis of these
      results we propose that HLA alleles constitute two separate classes: those that
      are TAP-efficient for peptide loading (HLA-B27, -A3 and -A24) and those that are
      TAP-inefficient (HLA-A2, -B7 and -B8). Computer modelling can be used to
      complement laboratory experiments and thereby speed up knowledge discovery in
      biology. In particular, we provide evidence that large-scale experiments can be
      avoided by combining initial experimental data with limited laboratory
      experiments sufficient to develop and validate appropriate computer models. These
      models can then be used to perform large-scale simulated experiments the results
      of which can then be validated by further small-scale laboratory experiments.

PMID- 11471245
TI  - In silico cloning of a new protein kinase, Aik2, related to Drosophila Aurora
      using the new tool: EST Blast.
AB  - In this short communication we report for the first time to our knowledge the use
      of ESTBlast to in silico clone a new gene and a step by step description of this
      particular in silico cloning project.

PMID- 11471246
TI  - An evolutionary classification of the metallo-beta-lactamase fold proteins.
AB  - All the detectable metallo-beta-lactamase fold proteins were identified in the
      publicly available sequence databases and complete genome sequences using
      iterative profile searches with the PSI-BLAST program and motif searches with
      position specific weight matrices. The catalytic site/mechanism and the
      corresponding structural elements were characterized for these proteins based on
      the available structure of the Bacillus zinc-dependent beta-lactamase. Based on
      pair-wise sequence and phylogenetic analysis an evolutionary classification for
      enzymes of this fold was developed and discussed in terms of implications for
      substrate specificity. Finally, some predicted inactive members which have been
      recruited for non-enzymatic functions such as microtubule binding in a
      cytoskeletal MAP1 are described.

PMID- 11471247
TI  - Use of contiguity on the chromosome to predict functional coupling.
AB  - The availability of a growing number of completely sequenced genomes opens new
      opportunities for understanding of complex biological systems. Success of genome
      based biology will, to a large extent, depend on the development of new
      approaches and tools for efficient comparative analysis of the genomes and their
      organization. We have developed a technique for detecting possible functional
      coupling between genes based on detection of potential operons. The approach
      involves computation of "pairs of close bidirectional best hits", which are pairs
      of genes that apparently occur within operons in multiple genomes. Using these
      pairs, one can compose evidence (based on the number of distinct genomes and the
      phylogenetic distance between the orthologous pairs) that a pair of genes is
      potentially functionally coupled. The technique has revealed a surprisingly rich
      and apparently accurate set of functionally coupled genes. The approach depends
      on the use of a relatively large number of genomes, and the amount of detected
      coupling grows dramatically as the number of genomes increases.

PMID- 11471248
TI  - Management of new onset atrial fibrillation.

PMID- 11471249
TI  - [The debut of neonatal medicine in the XIX century].
AB  - This article presents the birth of neonatal medicine during the XIXth century. A
      first generation of physicians, marked by clinic, observes the newborns and
      proposes some neonatal cares which innovate. But it is for essential from the
      1880's, around the generation of Pastorians formed in the "Ecole de la Maternite"
      of Paris (Tarnier) that a coherent procedure of neonatal cares is developed, with
      fight against infections, watching of feeding methods and warming up with
      incubators. The technical improvements allowed to solve some problems but the
      question of infection obstructed to go farer.

PMID- 11471250
TI  - [Sleeping sickness, a reemerging sickness].
AB  - Human African Trypanosomiasis (THA) has reappeared in most intertropical
      countries of Black Africa and an estimated 400,000 new cases are reported every
      year. Genetic tests which now make possible the differentiation of
      morphologically similar trypanosome subspecies showed that a large variety of
      game and domestic animals act as reservoir hosts of Trypanosoma brucei gambiense,
      thus making it even more difficult to fight the disease. The detection of cases
      and their treatment are absolutely necessary in preventing the spread of the
      disease. This can only be carried out with mobile medical teams which seek out
      patients. This detection currently calls on techniques which isolate trypanosomes
      and serological techniques. The collection of data with regards to different
      geographical positions, makes it possible to determine exactly which regions are
      affected, possibly affected or sound. Although the diagnosis of the hemo
      lymphatic stage can be determined without any great problem nowadays, the point
      at which the trypanosome invades CNS tissues and the ways in which it occurs are
      as yet unknown, even though the role of nitric oxyde and cytokines is better
      understood. Antibodies, anti-neurofilaments and anti-galactocerebrosides when
      found in the cerebro-spinal fluid are characteristic of the nervous stage of the
      disease. This condition is really sleeping sickness, not only hypersomnia. The
      more seriously the patient is affected the shorter the sleep-wake cycles are
      during the nycthemeron. These early disorders can be quickly reversed thanks to
      therapy, which to day uses melarsoprol, an arsenical drug, which cannot be of
      great promise as it is very toxic. Current research into nitro-imidazole
      derivatives (particularly megazol) seems a promising therapy as they were
      effective in vitro and in vivo, in rodents and primates.

PMID- 11471251
TI  - [Human pancreatic stem cell and diabetes cell therapy].
AB  - Cell therapy offers today important perspectives for the treatment of type 1
      diabetes. The current utilization of primary human islets of Langerhans
      nevertheless forbids all hope of developing this treatment on a large scale. The
      recent description of the persistence of stem cells capable of proliferating and
      differentiating in the adult pancreas offers an attractive alternative for the
      production in vitro of homologous insulin-secreting cells. We first reproduced in
      vitro from human islet preparations the proliferation of ductal epithelial
      structures and their progressive organization. Thereafter, we focused on the
      description of a reproducible source of human ductal cells by the
      transdifferentiation of exocrine preparations. More recently we described in
      these exocrine derived ductal cells the the expression the of insulin promoter
      factor-1 (IPF-1/otherwise known as PDX-1), a transcription factor essential for
      the differentiation of ductal cells into endocrine cells during both development
      and pancreatic regeneration. If the proliferation and differentiation of these
      cells is confirmed, this approach could lead to the description of an abundant
      source of human pancreatic stem cells for the production ex vivo of human insulin
      secreting cells and may even allow autologous cell therapy, in the absence of
      immunosuppression.

PMID- 11471252
TI  - The changing incidence of juvenile mitral stenosis and natural history of
      rheumatic mitral valvulitis in Al Baha, Saudi Arabia.
AB  - This study aimed to evaluate the impact of improved socio-economic conditions and
      health care on chronic mitral valve complications of rheumatic heart disease in
      Al Baha in the Kingdom of Saudi Arabia. Altogether, 190 cases of acute rheumatic
      fever (ARF) seen between 1982 and 1996 and 146 cases of symptomatic mitral
      stenosis seen between 1984 and 1996 were analysed. 2-D/Doppler echocardiography
      was used to evaluate the severity and progression of mitral regurgitation
      (MR)/mitral stenosis (MS). Of 90 cases of ARF who presented initially with MR,
      the murmur remained unchanged in 40%, increased in 30% and had decreased or
      disappeared in 30%. In cases with recurrence of ARF, mitral incompetence
      deteriorated in 16 of 26 cases (61.5%) and remained stable in ten (38%). Severe
      MS developed during follow-up in three cases of ARF, all aged less than 20 years.
      Seven of 50 cases (14%) of severe MS studied were aged 20 years or less. The 43%
      (25 of 58 cases) of severe cases of MS aged 20 years or less reported from King
      Faisal Hospital, Riyadh in 1981 compared with 14% of severe cases aged 20 years
      or less in this study indicates a significant slowing down of the rate of
      progression of MS following an attack of ARF in this region. Among individuals
      with MR during an ARF attack who reliably take their antibiotic prophylaxis, 70%
      will lose that murmur within 5 years of follow-up. In this series, only 30%
      showed a decrease or loss of MR and this probably reflects the degree of non
      compliance with secondary antibiotic prophylaxis in our cases. The rate of
      default from antibiotic prophylaxis was 32.6%.

PMID- 11471253
TI  - Congenital heart disease in 740 subjects: epidemiological aspects.
AB  - Between March 1997 and February 2000, 740 children with congenital heart disease
      (CHD) were studied in the Paediatric Cardiology Unit of King Fahad Hospital,
      Hofuf in Saudi Arabia. There were 351 boys and 389 girls (M:F ratio 0.9:1).
      Newborns accounted for 24% of cases and 53% of cases were detected in the 1st
      year of life. Ventricular septal defect was the commonest anomaly (39.5%),
      followed in descending order of frequency by atrial septal defect, pulmonary
      stenosis and patent ductus arteriosus. In general, the distribution of lesions
      was similar to that reported elsewhere in the world but there were fewer
      obstructive aortic lesions and transposition of the great arteries was rarer than
      in most other reports. The incidence of CHD showed no seasonal variation and Down
      syndrome was the commonest associated cause.

PMID- 11471254
TI  - Breastfeeding practices and attitudes relevant to the vertical transmission of
      HIV in rural south-west Uganda.
AB  - Breastfeeding has been associated with a doubling of the risk of HIV
      transmission. In developed countries, it is recommended that HIV-positive women
      do not breastfeed, but this is not a feasible option in most of Africa. It is
      therefore important to know the extent to which breastfeeding practices are
      amenable to change. To study this, we carried out 24 focus group discussions with
      208 women attending maternity clinics in three rural sites in rural south-west
      Uganda. Breastfeeding starts from a few minutes to a few days after delivery;
      most women reported starting after 2 days. The main reason for delay is lack of
      milk or that the breasts are 'blocked'. Most women thought that this delay was
      good for the baby, or at least not harmful. Almost all women reported giving the
      child a soup made of boiled mushrooms before starting to breastfeed. Once they
      have started breastfeeding, various supplementary foods are gradually introduced
      at 4-6 months. Women thought that ideally breastfeeding should last for 2-3
      years, but in practice most stopped after 18 months. The father and his female
      relatives generally decide when the child should be weaned. The women thought
      that commercial milk formula foods were good but could not use them because they
      are too expensive and anyway unavailable in rural areas. Most women were unaware
      that HIV could be passed to the child through breastfeeding. Various practices
      identified as potentially risky are common in this population. Artificial feeding
      is not a viable option in this area, and although women were prepared to make
      sacrifices to prevent vertical transmission of HIV, practices are deeply
      ingrained in traditional culture and will need to be addressed in future
      interventions. Male partners will also need to be involved.

PMID- 11471255
TI  - Infants exposed to alcohol prenatally: outcome at 3 and 7 months of age.
AB  - To investigate early recognition of the consequences of alcohol exposure in
      utero, we studied 79 infants at the ages of 3 and 7 months. Twenty-nine of them
      were exposed to varying levels of maternal alcohol intake and 50 had no exposure
      and formed a control group. Special attention was paid to fetal alcohol syndrome
      related facial features, neurological development and behavioural performance of
      the infants. To monitor facial features, pictures were taken at 3 and 7 months of
      age. Significant differences in facial features were found between the alcohol
      exposed and non-exposed children at 3 months only. An age-adequate neurological
      examination showed no significant difference at 3 months but a significant
      difference at 7 months of age between the alcohol-exposed infants and the
      controls. Mothers reported more misbehaviour in the exposed than in the non
      exposed group. These results indicate that it is possible to recognise alcohol
      related defects within the 1st year of life thus allowing early intervention.

PMID- 11471256
TI  - Comparison of two different severity scores (Paediatric Risk of Mortality [PRISM]
      and the Glasgow Meningococcal Sepsis Prognostic Score [GMSPS]) in meningococcal
      disease: preliminary analysis.
AB  - Two different illness severity scores, Pediatric Risk of Mortality (PRISM) and
      the Glasgow Meningococcal Sepsis Prognostic Score (GMSPS), were evaluated and
      compared in meningococcal disease in two paediatric intensive care units. Forty
      nine children with a median age of 36 months who had meningococcal sepsis
      confirmed by laboratory data were evaluated. Overall mortality was 18%. The
      median GMSPS was 3 in survivors and 8 in non-survivors. A GMSPS > or = 8 was
      significantly associated with death (p = 0.0001) with a mortality predictivity
      and specificity of 70% and 92.5%, respectively. The median PRISM score in
      survivors was 5.5 and 23 in non-survivors. A PRISM score of > or = 11 was
      significantly related to death (p < 0.0001). The Kendal correlation co-efficient
      between GMSPS and PRISM showed tau = 0.6859 (p = 0.0000). It is concluded that
      GMSPS and PRISM are useful methods for identifying and classifying children into
      low and high risk categories. GMSPS > or = 8 or a PRISM score > or = 11 are
      significantly predictive of mortality.

PMID- 11471257
TI  - Trend in childhood tuberculosis in Benin City, Nigeria.
AB  - In order to determine the trend in childhood tuberculosis, case records of
      children diagnosed and treated for tuberculosis between January 1981 and December
      1995 at the paediatric tuberculosis clinic of the University of Benin Teaching
      Hospital were reviewed. Of 8,829 paediatric medical cases, 1,026 (11.6%) were
      managed as tuberculosis. The proportion of tuberculosis cases increased steadily
      over the study period from 6.9% in 1981 to 22.1% in 1995. An apparent decrease in
      the number of cases in 1985 (6.6%) was attributable to a strike by medical
      personnel. The clinical pattern of tuberculosis during the study period shifted
      toward the adult type with disseminated and cavitating lesions predominating in
      later years. Additionally, the severity of the disease increased with the
      incidence of both haemoptysis and finger clubbing increasing from 1.6% in 1981 to
      14.2% and 18.2%, respectively, in 1995. Possible reasons for these findings
      include increased prevalence of malnutrition in childhood, increasing
      tuberculosis in the adult population and the effects of HIV/AIDS.

PMID- 11471258
TI  - Fatal, rotavirus-associated myocarditis and pneumonitis in a 2-year-old boy.
AB  - Rotavirus infection is common in childhood. We report a 2-year-old boy admitted
      to hospital with gastro-enteritis who suffered cardio-respiratory arrest and
      died. Autopsy showed evidence of rotavirus-associated myocarditis and
      pneumonitis. We are not aware of any previous report of death from this type of
      consequence of rotavirus infection.

PMID- 11471259
TI  - Antimicrobial resistance of nasopharyngeal isolates of Streptococcus pneumoniae
      in healthy carriers: report of a study in 5-year-olds in Marcory, Abidjan, Cote
      d'Ivoire.
AB  - The increasing prevalence of antibiotic-resistant Streptococcus pneumoniae is of
      growing public health concern. The aim of this study was to assess resistance
      rates of S. pneumoniae to penicillin and other antimicrobial agents. Between
      November 1997 and February 1998 in a community health centre in Marcory, an
      Abidjan suburb, 138 S. pneumoniae strains were isolated from the nasopharynxes of
      218 apparently healthy children aged 3-60 months. The sensitivity of the isolates
      was tested using the Kirby-Bauer method. In isolates with a possibly abnormal
      sensitivity to the Kirby-Bauer test, minimum inhibitory concentrations (MIC) were
      estimated using the E-test. Antimicrobials tested included penicillin G,
      amoxycillin, cefotaxime, cotrimoxazole, tetracycline, chloramphenicol,
      erythromycin, rifampicin and vancomycin. Twelve of 108 isolates (8.7%) had
      reduced sensitivity to penicillin G, and in three of them the MIC for penicillin
      reached at least 2 micrograms/ml. Resistance to amoxycillin and cefotaxime was
      lower than to penicillin (2.2%). With regard to cotrimoxazole, 37% were
      moderately resistant and 15.2% highly resistant. The lowest resistance rate
      observed was to rifampicin (2.2%) and the highest was to tetracycline (57.2%).
      Rates of resistance to erythromycin and chloramphenicol were 11.6% and 2.9%. All
      strains were sensitive to vancomycin. Multidrug resistance (MDR) was detected in
      9.4% of S. pneumoniae isolates. In children, epidemiological surveillance of
      resistance can be monitored by bacteriological surveys, as shown in this study.

PMID- 11471260
TI  - Splenectomy in thalassaemia major: experience at Madina Maternity and Children's
      Hospital, Saudi Arabia.
AB  - Eighteen (32%) of 56 children with thalassaemia major, whose ages ranged from 5
      to 12 years (mean 8.8), underwent splenectomy at Madina Maternity and Children's
      Hospital, Saudi Arabia during the period January 1992 to December 1999. This
      retrospective study was undertaken with the aim of discovering the outcome. The
      indications for splenectomy were increased transfusion requirements and massive
      splenomegaly in 17 children and splenic abscess in one. Polyvalent pneumococcal
      and Haemophilus influenza vaccines were not available and all the children
      therefore received intramuscular benzathine penicillin prophylaxis prior to
      surgery and oral penicillin prophylactically afterwards. Post-splenectomy
      septicaemia did not occur. The mean transfusion requirement reduced from 2 to 4
      weeks and the mean pre-transfusion haemoglobin rose from 6 to 9 g/dl. There were
      no deaths. We conclude that splenectomy can be performed safely in children over
      5 years of age with thalassaemia, and that pre- and post-operative penicillin can
      be given prophylactically in the absence of the recommended vaccines.

PMID- 11471261
TI  - Visceral leishmaniasis in Omani children: a review.
AB  - A retrospective study was undertaken of 33 children with visceral leishmaniasis
      admitted to Sultan Qaboos University Hospital (SQUH), Oman between 1993 and 1999.
      The aim was to study the epidemiological and clinical characteristics of visceral
      leishmaniasis in children in Oman. All presented with fever, anaemia and
      splenomegaly. Hepatomegaly and lymphadenopathy were present in 88% and 39% of
      children, respectively. All had iron deficiency anaemia. Hypertriglyceridaemia is
      a new observation. Diagnosis in all cases was confirmed by histological
      demonstration of Leishmania amastigotes in bone marrrow (32 subjects) or splenic
      aspirate (one subject). All children were treated with sodium stibogluconate, 14
      needed blood transfusion or blood products and all but two responded well. There
      were two deaths from associated complications (6% mortality).

PMID- 11471262
TI  - Hepatocellular carcinoma in Nigerian children.
AB  - Childhood primary hepatocellular carcinoma is rare and accounts for less than 1%
      of all abdominal malignancies in children < or = 14 years of age. A review of the
      records of the Cancer Registry, Ibadan, Nigeria covering the period 1960-1995 was
      scrutinised and 19 cases of hepatocellular carcinoma (HCC) were registered,
      accounting for 0.49% of all abdominal malignancies over the period of review. The
      mean (SD) age at presentation was 10.4 (3.0) years and the duration of illness
      before presentation was short. All the children presented late with abdominal
      distension and hepatomegaly as the major clinical features. Weight loss was
      evident in 80% of cases, splenomegaly occurred in 50% and jaundice was present in
      a third of them. The prognosis was poor; all the cases died within 2 weeks of
      presentation in hospital. There was evidence to suggest an association between
      hepatitis B virus infection and HCC in all the liver tissue stained by Shikata
      Orcein. This review shows that HCC, though uncommon, is important enough to be
      considered a possible cause of unexplained hepatomegaly in Nigerian children and
      that hepatitis B virus is an important aetiological factor. Though the number of
      cases under review is small, universal early vaccination against hepatitis B
      virus is necessary in Nigerian children in order to reduce the burden of chronic
      hepatitis B disease and hepatocellular carcinoma.

PMID- 11471263
TI  - Tympanic thermometry in Nigerian children.
AB  - Rectal and aural temperatures were recorded at the same time in 378 children aged
      < or = 60 months and were found to be similar across the various age groups,
      correlation coefficients (r) ranging from 0.61 to 0.91. The mean differences
      between rectal and aural temperatures varied between -0.06 and 0.25 degree C.
      Concordance between the two methods ranged from 88.9% to 98% across the
      temperature range. Tympanic thermometry is simpler, safer and quicker than rectal
      thermometry and these findings justify the use of aural thermometry in any busy
      clinical facility for children.

PMID- 11471264
TI  - Group A beta-haemolytic streptococcal acute chest event in a child with sickle
      cell anaemia.
AB  - Acute chest syndrome is a major cause of death and hospitalisation in children
      with sickle cell anaemia. It is often initiated by an infection, particularly
      pneumonia. Microbial agents previously not associated with acute chest syndrome
      are becoming increasingly important. Group A beta-haemolytic Streptococcus
      (GABHS) is thought to be an uncommon cause of pneumonia in children with sickle
      cell anaemia. We report a 15-year-old African-American girl who presented with an
      acute chest event characterised by fever, cough, chest pain, shortness of breath,
      right upper abdominal quadrant pain, jaundice and otitis media. Chest radiograph
      showed multi-lobar pneumonia with left pleural effusion. Group A beta-haemolytic
      Streptococcus was isolated from culture of pleural and middle ear fluids. She
      responded to therapy that included antibiotics, exchange blood transfusion,
      oxygen, thoracotomy chest tube drainage and decortication. In a child with sickle
      cell anaemia presenting with fever and an acute chest event, pneumonia should be
      considered and GABHS recognised as a possible aetiological agent. In addition, a
      chest X-ray should be obtained and antibiotics against agents causing community
      acquired pneumonia instituted.

PMID- 11471265
TI  - Cortical bone mineral density in asymmetrical mandibles: a three-dimensional
      quantitative computed tomography study.
AB  - The three-dimensional distribution (3D) of the highest mineralized cortical bone
      was evaluated in 32 subjects between the ages of 8 and 30 years with asymmetrical
      mandibles using quantitative computed tomography (QCT). The geometrical
      distribution of the highest mineralized areas (> 1250 mg/cm3) representative of
      mandibular cortical bone was determined by 3D reconstruction of the images. The
      length of the mandible on each side was determined by defining a new linear
      measurement from the centre of the 3D reconstructed condyle to the midline of the
      symphysis as identified from a submental view. The cross-sectional areas of the
      masseter and medial pterygoid muscles were assessed from bilateral axial views
      through the middle of the muscles parallel to the Frankfort-Horizontal plane.
      Comparison between the lengths of the two mandibular sides (right-left = mm)
      indicated a range of asymmetries with an equal number of subjects with the left
      and right mandible longer. Comparison of the area of highest mineralized cortical
      bone between the right and left sides (R/L) to the ratio of the mandibular length
      (R/L) showed a high correlation coefficient (r = 0.629) suggesting that the
      shortest mandibular side had more highly mineralized bone. A comparison of the
      area of highest mineralized cortical bone between the right and left sides (R/L)
      to the ratio of cross-sectional areas of the muscles showed the highest
      correlation coefficient (r = 0.724) with the ipsilateral masseter muscle. These
      findings indicate that asymmetrical mandibles are associated with asymmetrical
      distributions of the highest mineralized cortical bone and that this is age
      dependent.

PMID- 11471266
TI  - The influence of bracket type on the force delivery of Ni-Ti archwires.
AB  - This study investigated the force delivery of an 0.014 inch nickel-titanium (Ni
      Ti) archwire used in combination with a range of commercially available bracket
      systems, and using a model based on an 'ideal' mandibular archform. The model
      aimed to replicate the clinical interbracket span. The force delivery was
      measured at four different sites on an archwire for one batch of 10 nickel
      titanium archwires from one manufacturer, using one bracket/archwire combination.
      The four sites represented the lateral incisor, canine, second premolar and first
      molar positions. Force delivery was also measured for a further four different
      bracket designs at four different sites on the archwire using five fresh wires of
      the same archwire type. The wires were loaded with an M5 Nene Universal testing
      machine. The results demonstrate that the peak and plateau force, both of which
      are clinically important, are dependent on several factors of the
      archwire/bracket combination. The results showed that 20 per cent of the batch of
      10 wires behaved differently by delivering a higher peak force. There was a
      statistically significant difference (P < 0.05) between the four bracket/archwire
      combinations for the peak forces delivered, but there was very little difference
      between the four bracket/archwire unloading force delivery values. The wires
      delivered a predictable force on the unloading curves, but self-ligating brackets
      may not develop sufficient strain within the wire to take full advantage of the
      superelastic effect of Ni-Ti wires.

PMID- 11471267
TI  - An in vitro investigation into the use of resin-modified glass poly(alkenoate)
      cements as orthodontic bonding agents.
AB  - This in vitro study was designed to determine the effect of time on the measured
      mean force to debond when brackets were bonded using resin-modified glass
      poly(alkenoate) cements and to compare them with a light-cured diacrylate.
      Changes in surface topography and composition of the cements were also
      investigated. Stainless steel orthodontic brackets were bonded to 160 upper
      premolar teeth in four test groups: Transbond, Fuji Ortho LC, and 3 M Multi-Cure
      with and without enamel etching. Shear bond testing to failure was performed
      after 1 hour, 1 week, 1 month, and 1 year. The first three groups were then
      rebonded and stored for the same time periods before being shear tested again.
      Debond force was recorded in Newtons and the locus of bond failure was scored
      using the Adhesive Remnant Index (ARI). Surface topography and composition of the
      test materials were also studied at time periods of 1 day, and 1, 6, and 18
      months, using scanning electron microscopy (SEM) and energy dispersive X-ray
      analysis (EDAX). The mean force to debond (N) was observed to increase with time
      in all four test groups, with there being little significant difference between
      the groups. When the same brackets were rebonded, the mean force to debond
      reduced. Surface topography and compositional changes over time were only
      observed with the resin-modified glass poly(alkenoate) cements. Resin-modified
      glass poly(alkenoate) cements have a mean force to debond comparable with
      diacrylate bonding agents. However, unlike diacrylates they undergo surface
      changes with time, the significance of which is unknown.

PMID- 11471268
TI  - A model for evaluating friction during orthodontic tooth movement.
AB  - Orthodontic forces for sliding tooth movement during space closure are applied at
      a distance from the centre of resistance of the teeth. For this reason, the teeth
      will tip until contacts are established between the archwire and diagonally
      opposite corners of the bracket wings. They will also rotate until the wire
      contacts opposite corners of the ligature tie or the buccal shield with self
      ligating brackets, and the base of the slot. Frictional forces measured with
      models that do not enable such movements may therefore not be representative of
      the clinical condition. To test this hypothesis, a dentoalveolar model that
      allowed accurate reproduction of the width of a material of similar elastic
      properties as the periodontal ligament (PDL) was fabricated. In addition, a
      device was designed that allowed accurate adjustment of the bracket slot in all
      three planes of space during mounting of the model in an Instron machine.
      Frictional forces during sliding of ceramic brackets with 0.022 x 0.028-inch
      bracket slots along 0.019 x 0.025-inch stainless steel wires were tested using
      models with simulated PDL widths of 0.00, 0.33, 0.67, and 1.00 mm. ANOVA detected
      a significant effect of PDL width on mean frictional force (P < 0.001). Pairwise
      comparisons at 0.05 significance level indicated no differences between the
      models without PDL and those with a width of 0.33 mm, and between models with PDL
      widths of 0.67 and 1.00 mm. However, the two models with smaller widths produced
      significantly lower frictional forces.

PMID- 11471269
TI  - Location of the centre of resistance of the upper dentition and the nasomaxillary
      complex. An experimental study.
AB  - The purpose of this study was to investigate the initial displacement of the
      upper dentition and the nasomaxillary complex as a result of different directions
      of force application, and to determine the initial centres of resistance for both
      the upper dentition and the nasomaxillary complex. A macerated human skull with a
      well-aligned upper arch was used as one experimental model and Araldit 208 as a
      substitute for the periodontal ligament (PDL). Specifically designed 'antenna
      headgear' was developed in an attempt to create different points of force
      application to simulate high-pull and horizontal traction, and orthopaedic force
      magnitudes of 8 N were applied to the upper dentition and the nasomaxillary
      complex. Double exposure holography was used to measure the initial displacement.
      Reproducibility of the technique was tested and found to be reliable. According
      to the registered fringe patterns, the force application transmitted by the
      headgear resulted in complex displacement of facial bones. Pure translation of
      the maxilla and the upper dentition was observed when the force vector passed by
      in the area of the key-ridge. No obvious difference was found between the centre
      of resistance of the upper dentition and the nasomaxillary complex. The location
      of two different centres of resistance could not be confirmed by measuring
      initial displacements on this macerated human skull.

PMID- 11471270
TI  - Facial growth: separating shape from size.
AB  - Optical surface scanning technologies produce dense three-dimensional (3D) data
      sets, which allow detailed analysis of surface morphology. This paper describes a
      method of analysing change in facial shape independently of change in size. The
      3D data from three male subjects from the age of 6-21 years were recorded using
      an optical surface scanner. A series of 22 conventional landmarks were located
      with the aid of horizontal and vertical profiles across the face, and were
      analysed using geometric morphometrics. The 3D landmark co-ordinates were scaled
      and aligned using Generalized Procrustes Analysis (GPA) and analysed by Principal
      Component Analysis (PCA) to determine the shape change over the growth period for
      each individual. The results show that the centroid size reaches a steady value
      at different times for each of the subjects. When analysing shape versus age,
      highly significant correlations were found with principal component 1 (PC-1), but
      not with other principal components. PC-1 encompassed 40 per cent of the total
      variance for each subject. The movement of facial landmarks with time that is
      represented by PC-1 in each of the individuals is described. The use of these
      techniques has enabled the individual characteristics of facial growth to be
      identified and also has revealed the subtle changes in shape that continue after
      change in size has ceased.

PMID- 11471271
TI  - Analysis of Holdaway soft-tissue measurements in children between 9 and 12 years
      of age.
AB  - In this study, 43 lateral cephalometric radiographs from 20 boys and 23 girls
      subjects were used to determine the Holdaway soft tissue growth changes. Subjects
      with Class I occlusions, balanced skeletal profiles, normal growth and
      development, and no orthodontic treatment history were included in the
      investigation. The cephalometric measurements were carried out on the first and
      second radiographs of each subject, with an average interval of 5 years. The
      growth changes in both sexes were analysed separately. The changes resulting from
      growth and development were determined by a paired t-test. The results showed
      that all measurements were significant at various levels except for upper lip
      sulcus depth, subnasal-H line distance, and lower lip H distance in girls, and
      upper lip sulcus depth, subnasal-H line distance, H angle and lower lip H line
      distance in boys. The measurement differences were observed with a Student's t
      test. No significant difference was found for any measurement except upper lip
      base thickness (P < 0.001) and upper lip thickness (P < 0.01). The following
      measurements during the observation period were statistically different: soft
      tissue facial angle (P < 0.01 in girls, P < 0.05 boys), nose prominence (P <
      0.001 in girls and boys), skeletal profile convexity (P < 0.001 in girls, P <
      0.01 in boys), basic upper lip thickness (P < 0.001 in girls and boys), upper lip
      thickness (P < 0.05 in girls, P < 0.001 in boys), H angle (P < 0.001 in girls),
      lower lip sulcus depth (P < 0.001 in girls and boys), and soft-tissue chin
      thickness (P < 0.001 in girls, P < 0.001 in boys).

PMID- 11471272
TI  - The influence of orthodontic extraction treatment on dental structures: a two
      factor evaluation.
AB  - The purpose of this investigation was to evaluate the effects of different growth
      patterns and treatment types on dentoalveolar structures in patients treated with
      fixed Edgewise mechanics and the extraction of four first premolars. A total of
      41 patients with a mean chronological age of 14 years 7 months and skeletal age
      of 14 years 6 months were included in the study. The type of growth pattern was
      assessed as mesio- or hyper-divergent, and the treatment type as the use or non
      use of headgear. The results were analysed by two-way analysis of variance
      (ANOVA). The decrease in overbite in the mesiodivergent group was statistically
      significant when compared with the increase in the hyper-divergent group (P <
      0.01). Extrusion of the lower molar was observed in all groups, and a
      statistically significant difference was found between the mesio- and hyper
      divergent groups (P < 0.05). Interaction between growth pattern and treatment
      type was not found to be significant for any variable. It can be concluded that
      premolar extractions and the use of headgear with fixed appliances does not
      significantly change the overjet, occlusal plane angle, upper and lower anterior
      dentoalveolar heights, upper posterior dentoalveolar height, or the inclination
      of the upper and lower incisors. The only significant changes were observed in
      overbite as a result of treatment mechanics and in lower posterior dentoalveolar
      height due to the growth pattern.

PMID- 11471273
TI  - Tightness of dental contact points in spaced and non-spaced permanent dentitions.
AB  - One of the characteristics of normal occlusion is tight dental contact points
      (CPs). However, the magnitude and distribution of the tightness of a dental
      contact point (TDCP) in non-spaced versus spaced dentitions are unknown, as well
      as the mechanism controlling this arrangement. Two hypotheses were examined: the
      compression theory, i.e. the teeth touch each other in a compressive state; and
      the resistance theory, i.e. size and number of roots determine TDCP values. For
      the study, 60 subjects (27 men, 33 women), mean age 25 +/- 4.3 years, with a
      complete permanent dentition and no missing teeth were divided into spaced (n =
      22) and non-spaced dentitions (n = 38). For each CP, four repeated measurements
      of peak strain were performed with a one-month interval. No significant
      differences were found between repeated measurements. All CPs demonstrated a
      continuous decreased TDCP in the postero-anterior direction. Consequently, in non
      spaced dentitions TDCPs between molars were 100 per cent higher than incisors.
      The five anterior CPs of each jaw demonstrated similar TDCP values. Maxillary
      TDCPs versus mandibular antagonists were not significant. Mandibular TDCPs were
      significantly higher in men than in women (14 per cent). Anterior TDCPs were less
      in spaced than in non-spaced dentitions (55 per cent). Posterior TDCPs were also
      lower in spaced dentitions, however, to a lesser extent (25 per cent). With the
      exception of TDCPnon-spaced > TDCPspaced, which is partially explained by the
      compression theory, most of the findings support the resistance theory regulating
      TDCP characteristics of the permanent dentition.

PMID- 11471274
TI  - Professional perceptions of the benefits of orthodontic treatment.
AB  - The aim of this study was to assess general dental practitioners' and
      orthodontists' perceptions of the benefits of orthodontic treatment. A specially
      designed questionnaire was sent to a random sample of 150 general dental
      practitioners (GDPs) and all orthodontists in Northern Ireland (excluding
      hospital practitioners) with a postgraduate qualification (n = 29). There was a
      93 per cent response rate by the general dental practitioners and all but one
      specialist practitioner returned the questionnaire. The questionnaire comprised
      14 visual analogue scales (VAS) whereby participants were asked to rate the
      importance of various possible dental health and psychosocial benefits of
      orthodontic treatment. In addition to the VAS, the influence of dentist variables
      such as number of years since qualification, orthodontic cases completed,
      referral rates and attendance at postgraduate lectures were examined. When
      ratings on the 14 dental health and psychosocial scales were examined overall,
      GDPs rated an improvement in self-esteem while orthodontists considered an
      improvement in physical attractiveness as the most important benefit of
      orthodontic treatment. Even though psychosocial variables received the highest
      ratings, examination of the mean ratings (and 95 per cent confidence intervals)
      revealed that some dental health factors were also rated highly by both groups.
      While the results do indicate an encouraging awareness of the psychosocial
      benefits of orthodontic treatment, they also suggest that both GDPs and
      orthodontists have an unrealistic expectation of the dental health gain likely to
      result from orthodontic treatment.

PMID- 11471275
TI  - [Assessment of antihypertensive compliance using a self-administered
      questionnaire: development and use in a hypertension clinic].
AB  - OBJECTIVE: The most practical method of assessing medication compliance is to ask
      the patient for a self-report; but the interview question has to be selected and
      validated. The aim of this work was to select and validate interview questions to
      be used in a self-administered questionnaire for measurement of medication
      compliance in hypertensive patients. PATIENTS AND METHODS: In 117 treated
      hypertensive patients, we compared an interview question to a clinical evaluation
      of medication compliance. Kappa indices were calculated to test the concordance
      between interview question and medication compliance. In 184 patients treated for
      hypertension since at least a year, the validated self-report was compared to a
      clinical evaluation of medication compliance. RESULTS: Interview questions were
      not equally sensitive for detection of medication compliance and 6 questions were
      included in the Compliance Evaluation Test (CET). In 184 patients, we compared
      the results obtained with CET to clinical evaluation of medication compliance.
      Values of kappa indices were above 0.5 in "good compliance" when "No" was
      answered to the 6 items, in "minor noncompliance" when 1 or 2 "Yes" were given,
      in "noncompliance" when 3 or more "Yes" were given. In this population of
      hypertensive patients followed in a hypertension clinic, we observed 10%
      "noncompliance", 24% "minor noncompliance", and 66% "good compliance".
      CONCLUSION: In clinical practice, interview may be the most useful method of
      measuring medication compliance. We demonstrated that the compliance evaluation
      test is validated and may help physicians to face the problem of nonadherence
      among their hypertensive patients.

PMID- 11471276
TI  - [Acute sinusitus in adults. Management by general practitioners].
AB  - OBJECTIVE: Acute sinusitis is a common condition encountered in general practice
      and raises the question of appropriate management. Sufficient data are still
      lacking in the literature to provide a fully satisfactory response. METHODS: We
      conducted a survey among 193 physicians representative of the general
      practitioners in France to collect 755 cases of acute sinusitis treated in the
      outpatient setting from January 6 through March 15, 1999. We recorded clinical
      features and therapeutic management. RESULTS: Pain was the predominant clinical
      sign (97% of the patients). Facial pain with a highly suggestive localization and
      aggravated by pressure and headache were the most frequent. Most of the patients
      also had a nasal symptom (77%) and an infectious context (90%). Three
      circumstances had been pre-defined by the experts: unique acute sinusitis, acute
      episode of chronic sinusitis, and recurrent acute sinusitis. In 67% of the cases
      of unique acute sinusitis, the diagnosis of the general practitioner was
      confirmed a posterori by the experts. Few complementary tests were ordered (in
      17% of the patients) mainly in fragile patients and mainly limited to a
      radiography of the sinus (81% of the complementary tests ordered). An oral
      antibiotic was almost always prescribed (96% of the patients) although
      antibiotics comprised only 29% of all prescriptions. General corticosteroid
      therapy (41%), local treatment (73%) and anti-cough or expectoration medications
      (52%) were also prescribed. Despite the painful nature of sinusitis, analgesics
      were only prescribed for 36% of the patients. CONCLUSION: This observational
      survey enabled us to describe the diagnostic and therapeutic strategy used by
      French general practitioners for acute sinusitis in adults. There was general
      agreement on the strategy that was well adapted to the patient profiles. An
      evaluation of the different classes of drugs prescribed, and their efficacy in
      the outpatient setting, that remains to be determined, was not however attempted.

PMID- 11471277
TI  - [Graded classification of acute chloralose poisoning. 509 cases].
AB  - OBJECTIVE: The annual incidence of chloralose poisoning has exceeded 3 cases per
      100,000 inhabitants in Tunisia since 1997. The purpose of this study was to
      analyze clinical features of chloralose poisoning. METHODS: We reviewed patients
      admitted to the intensive care unit during the last 5 years to search for
      chloralose poisoning. The identified cases were classed into 5 grades by clinical
      features: depth of coma, characteristics of the myoclonia, and cerebral trunk
      reflex response. RESULTS: We identified 509 cases of chloralose poisoning over
      the last 5 years. Seventy-five patients (14.7%) were in grade 1: drowsiness
      alone. Four hundred ten patients (80.8%) were in grades 2 and 3: hypertonic coma
      and myoclonus. The clinical course was favorable after sedation, tracheal
      intubation and mechanical ventilation. Twenty-three patients (4.6%) were in
      grades 4 and 5: hypertonic coma (Glasgow coma score = 3). Three of them died.
      CONCLUSION: The clinical features of chloralose poisoning depend on the ingested
      dose. Despite the gravity of the initial clinical presentation, prognosis is
      excellent if symptomatic treatment is given early, even in grade 5 cases which
      simulate brain death.

PMID- 11471278
TI  - [Pseudomonas aeruginosa osteitis of the spinal process after peridural
      anesthesia].
AB  - BACKGROUND: Osteitis of the posterior wall of the spinal canal is an exceptional
      complication after peridural anesthesia. Prognosis depends on early diagnosis
      based on clinical signs and imaging data. CASE REPORT: A 73-year-old man was
      hospitalized for lower back pain and fever of 3 weeks duration after a total hip
      arthroplasty performed under general anesthesia. Computed tomography and magnetic
      resonance imaging of the lumbar spine disclosed osteitis of the spinal processes.
      Local bacteriology sample evidenced Pseudomonas aeruginosa. Outcome was favorable
      after a 6-month treatment. DISCUSSION: Data in the French and English literature
      (since 1948) on bone infections following epidural anesthesia have included 5
      cases of spondylodiscitis and 1 case of posterior wall osteitis. The diagnosis is
      suggested by the clinical presentation. Standard x-rays contribute little. Early
      diagnosis in the infraradiological phase can be obtained with bone scintigraphy.
      Computed tomography or magnetic resonance imaging are currently highly
      contributive to diagnosis and follow-up after treatment. Contamination may be
      direct or via the blood stream or result from an extension of a neighboring
      infectious focus. Antibiotic therapy and immobilization are indicated. Rigorous
      application of strict aseptic procedures during lumbar puncture and use of the
      epidural catheter are crucial for prevention.

PMID- 11471279
TI  - [Interstitial pneumopathy due to flecainide].

PMID- 11471280
TI  - [Should cross matching be sensitized before kidney transplantation?].

PMID- 11471281
TI  - [Lymphocytic colitis after ingestion of Rustacea flavonoid extract].

PMID- 11471282
TI  - [An experience in teaching pharmacology on the internet].
AB  - Internet and Intranet are omnipresent in the University world. We developed an
      easy-access website (www.med.univ-rennes1.fr/etud/pharmaco) devoted to teaching
      pharmacology and report here our experience after 4 years of use. Our objective
      was to determine the value of this new teaching tool in the medical coursus. The
      site is entirely free and presents approximately 50 topics and diaporamas
      discussing various themes: the cell, the receptor, general pharmacology, clinical
      research, population research, drug classes, etc. Harbored by the Medical
      Informatics Laboratory of the University of Rennes Medical School, this site
      serves as a reference for medical students and others. More than 100 visits are
      recorded daily, approximately half from visitors outside France. The advantages
      of this new teaching tool, which operates within the framework of a Virtual
      Medical University project, are evident for students and professors alike. Its
      impact on the quality of drug therapy by future doctors remains to be determined.

PMID- 11471283
TI  - [Buruli ulcers: 14 cases in 5 weeks in rural Benin].

PMID- 11471284
TI  - [Angiotensin II receptor antagonists: different or equivalent?].
AB  - ARA-II: Angiotensin II receptor antagonists (ARA-II) belong to a recent class of
      antihypertensive drugs whose mechanism of action is similar to converting enzyme
      inhibitors (CEI). ARA-II are particularly interesting due to the excellent
      clinical and biological tolerance, similar to placebo, and their antihypertensive
      efficacy, comparable with classical drug classes. PUBLISHED TRIALS: A meta
      analysis, published by Conlin in the American Journal of Hypertension, suggests
      that ARA-II, specifically losartan, valsartan, irbesartan and candesartan, have
      an equipotent blood pressure lowering effect. The careful lecture of this meta
      analysis however discloses a faulty methodology from which no valid conclusion
      can be drawn. Since this early publication, several other comparative studies
      have been published. These multicentric, randomized double-blind studies enrolled
      a sufficient number of patients and demonstrated a clinical difference between
      certain ARA-II at usual dosages. CLINICAL PRACTICE: These studies do have an
      impact on everyday practice. For the practitioner, the goal is to obtain and then
      maintain a long-term and optimal reduction in the blood pressure level (reduction
      or prevention of target-organ disorders and cardiovascular complications of high
      blood pressure). This reduction in the cardiovascular risk will also depend
      directly on tolerance and compliance to the antihypertensive treatment. This
      element must also be considered in assessing treatment efficacy, independent of
      the blood pressure lowering effect. The results of several other studies will be
      published in 2001-2003. These large-scale studies on ARA-II related morbidity and
      mortality will be most useful in determining the role of these drugs in different
      therapeutic strategies compared with other drug classes.

PMID- 11471285
TI  - [Oxidative stress and human disease. Current knowledge and perspectives for
      prevention].
AB  - DYNAMIC BALANCE: The antibiotic status of the human organism results from the
      dynamic balance between the antioxidant system and the production of reactive
      oxygen species. Oxidative stress occurs when this balance shifts in favor of pro
      oxidants as can occur in several disease situations. ROS: Part of the oxygen used
      by cells is transformed into toxic metabolites, reactive oxygen species (ROS),
      which can be the cause or consequence of tissue and molecular disorders. Some of
      the most prominent diseases linked with oxidative stress include atherosclerosis,
      cancer, allergy, neurodegenerative diseases, Parkinson's disease. PERSPECTIVES
      FOR PREVENTION: Actions designed to prevent the environmental cause, such as
      eviction of a exposure to toxins or a change in eating habits, can be an
      effective means of reducing the lesions induced. Study of total antioxidant
      potential could be quite useful for detecting and monitoring environmental damage
      and for clinical follow-up. It could also help in determining, for each
      individual, the negative or positive development of a therapy on the anti-free
      radical action. Treatments must be personalized according to the tested response.

PMID- 11471286
TI  - [Fortuitous discovery of lipothymoma in a patient with back pain].

PMID- 11471287
TI  - [Radiological diagnosis in polytrauma: interdisciplinary management].
AB  - The presence of a radiologist within the admitting area of an emergency
      department and his capability as a member of the trauma team have a major impact
      on the role of diagnostic radiology in trauma care. The knowledge of clinical
      decision criteria, algorithms, and standards of patient care are essential for
      the acceptance within a trauma team. We present an interdisciplinary management
      concept of diagnostic radiology for trauma patients, which comprises basic
      diagnosis, organ diagnosis, radiological ABC, and algorithms of early clinical
      care. It is the result of a prospective study comprising over 2000 documented
      multiple injured patients. The radiologist on a trauma team should support trauma
      surgery and anesthesia in diagnostic and clinical work-up. The radiological ABC
      provides a structured approach for diagnostic imaging in all steps of the early
      clinical care of the multiple injured patient. Radiological ABC requires a
      reevaluation in cases of equivocal findings or difficulties in the clinical
      course. Direct communication of radiological findings with the trauma team
      enables quick clinical decisions. In addition, the radiologist can priority
      oriented influence the therapy by using interventional procedures. The clinical
      radiologist is an active member of the interdisciplinary trauma team, not only
      providing diagnostic imaging but also participating in clinical decisions.

PMID- 11471288
TI  - Implantation of a new access device for hemodialysis (Dialock): initial
      experience in 5 patients.
AB  - PURPOSE: A new hemodialysis access port system was implanted. METHODS: The
      Dialock consists of a port-like double-valve, implanted subcutaneously below the
      clavicle, which is attached to two catheters, placed in the right atrium via the
      jugular vein. The device has been implanted in 5 patients (4 female, 1 male).
      RESULTS: In all 5 patients the implantation of the catheters and the port was
      technically successful. Total average duration of dialysis was 3.6 months. Two
      patients developed a port pocket hematoma 10-14 days post implantation, one of
      them required surgical revision. One port was explanted due to septicemia,
      whereas a port infection was not confirmed. One patient showed a thrombotic
      occlusion of both catheter tips 8 days after implantation, fixed by catheter
      exchange. Another patient presented with slight migration of the port catheters,
      which was managed by refixation of the port within the pocket. Beside these
      complications, the devices were working well. CONCLUSION: The Dialock system
      offers an interesting alternative to external catheters for hemodialysis. With
      respect to the complications it deserves further studies to determine its future
      role in the field of vascular access.

PMID- 11471289
TI  - [Extravasation of contrast media in brain parenchyma and cerebrospinal fluid
      space after CT or DSA of thorax or abdomen].
AB  - PURPOSE: Analysis of clinical and CT findings in patients with signs of
      disruption of the blood-brain or blood-CSF barrier after i.v. or i.a.
      administration of non-ionic contrast media. METHODS: 1. Retrospective analysis of
      8 patients with clinical and CT findings of disruption of the blood-brain or
      blood-CSF barrier after i.v. or i.a. administration of non-ionic contrast media
      (200-450 ml). 2. Prospective analysis of 30 intensive care patients with sepsis
      and suspected abscess, who underwent CT of the chest and abdomen with 240 ml of a
      non-ionic contrast medium followed by cranial CT to rule out septic lesions.
      RESULTS: The retrospective analysis proved that disruption of the blood-brain
      barrier may occur in elderly patients with risk factors after injection of higher
      amounts of contrast media. In the prospective study, equivalent CT phenomena were
      observed in 3 of 30 patients with sepsis. CONCLUSIONS: Hypoxemic and toxics
      damage to the blood-brain barrier as well as higher amounts of contrast media may
      result in extravasation of contrast medium into the CSF space, which can be
      demonstrated by CT. For differential diagnosis, the clinical symptoms and CT
      patterns of a disruption of the blood-brain or blood-CSF barrier should be known.

PMID- 11471290
TI  - [MRI with cerebrospinal fluid measurement before and after endoscopic
      ventriculostomy and aqueductal stenosis].
AB  - PURPOSE: Evaluation of MR imaging and CSF flow measurement for planning and
      follow-up of neuroendoscopic third ventriculostomy in occlusive triventricular
      hydrocephalus. METHOD: 17 patients with occlusive hydrocephalus due to idiopathic
      or neoplastic aqueductal stenosis were examined before and after surgery with
      cardiac-gated T2-weighted and cardiac-gated phase contrast cine sequences. The
      visibility of anatomic structures and the patency of the ventriculostomy were
      evaluated. RESULTS: In all 17 patients, the relevant anatomic structures were
      visible. The cine sequence demonstrated occlusion of the aqueduct and patency of
      the ventriculostomy in all cases, even in patients with doubtful clinical
      patterns. CONCLUSIONS: MR imaging with additional cardiac-gated cine sequences
      allows exact preoperative diagnosis of occlusive hydrocephalus as well as patient
      selection and planning for endoscopic third ventriculostomy. Non-invasive follow
      up, especially in patients with a doubtful clinical pattern, is possible.

PMID- 11471291
TI  - [Creutzfeldt-Jakob disease: value of MRI].
AB  - PURPOSE: To define the role of MRI in the diagnosis of Creutzfeldt-Jakob disease
      (CJD). METHODS: 14 patients with suspected CJD were studied within 3 years. MRI
      findings were correlated with WHO established diagnostic criteria (clinical
      findings, EEG, CSF with 14-3-3 protein assay). RESULTS: 12 patients had CJD. One
      patient each suffered from Hashimoto's encephalitis and ALS dementia complex,
      respectively. Nine of 12 CJD patients had increased signal intensity of the
      striatum (n = 8), pulvinar thalami (n = 5) and/or cerebellar and cerebral cortex
      (n = 3), respectively. Signal intensity was most pronounced on FLAIR sequences;
      six patients were studied with diffusion-weighted MRI and showed impaired
      diffusion in these areas. Both patients without CJD did not show the
      abovementioned signal changes (sensitivity 75%, specificity and positive
      predictive value 100%, respectively). CONCLUSION: If patients with suspected CJD
      are studied with FLAIR and diffusion-weighted sequences, this disorder can
      reliably be proven or ruled out. Typical MRI findings narrow down the
      differential diagnosis and should be included in the WHO diagnostic criteria.

PMID- 11471292
TI  - [Similarity of the brains of twins].
AB  - PURPOSE: To test the assumption underlying every morphometric twin study that the
      brains of monozygotic twins are almost identical. METHODS: High resolution MRI of
      the neurocranium of 26 monozygotic twin pairs were acquired and the volumes of 36
      cerebral structures were measured. The same twins served as control group after
      rear-ranging them into non-related pairs of same sex and matching them for age,
      body height and body weight. RESULTS: For most of the examined structures the
      correlations within the twins were significant (R = 0.97-0.59). Except for total
      forebrain volume the controls showed no significant similarity. CONCLUSIONS: For
      almost every measured cerebral structure the assumption, that significant
      similarities exist between healthy monozygotic twins is correct. Therefore
      discordant monozygotic twins represent an excellent sample when investigating
      cerebral correlates of neurologic and psychiatric disorders.

PMID- 11471293
TI  - [MR angiography in diagnosis of vasculitis and benign angiopathies of the central
      nervous system].
AB  - PURPOSE: To evaluate TOF 3D magnetic resonance angiography (MRA) of the
      intracranial arteries in patients with vasculitis or vasculitis-like benign
      angiopathy of the central nervous system (CNS). METHOD: The results of MRA in 20
      patients with clinically and radiographically proven vasculitis (17/20) or
      vasculitis-like benign angiopathy (3/20) of the CNS were retrospectively
      analysed. Patients with hyperintense lesions of more than 3 mm on T2-weighted MRI
      images were included in this trial. An inflammatory, embolic, neurodegenerative
      or metastatic origin of these lesions was excluded by extensive clinical studies.
      For the MR-examination a TOF 3D FISP sequence was used on a 1.5 T imager.
      RESULTS: MRA showed characteristic changes for vasculitis or angiopathy in 15 of
      20 patients (75%). CONCLUSIONS: In patients suspected of having a vasculitis or
      vasculitis-like angiopathy, MRA is recommended as a non-invasive modality. If the
      results of MRI and extensive clinical studies are carefully correlated, MRA may
      substitute conventional angiography in cases with typical vascular changes.

PMID- 11471294
TI  - [Diagnosis of lung embolism and underlying venous thrombosis in multi-slice
      spiral CT].
AB  - AIM: To determine the value of multi-slice CT for the diagnosis of acute
      pulmonary embolism and an underlying venous thrombosis. METHODS: 70 patients with
      clinically suspected acute pulmonary embolism were examined. Using multi-slice CT
      a combined examination of the pulmonary arteries and the veins of the lower limb,
      pelvis and abdomen was performed. Only one single bolus of 150 ml iopromid 300
      was injected into a cubital vein with a flow of 4 ml/s. First, the pulmonary
      arteries were scanned with a slice thickness of 2.5 mm and a pitch of 1.5. On
      arrival of the contrast medium at the popliteal veins, indicated by bolus
      trakking, the veins of the lower limbs up to the end of the inferior vena cava
      were imaged using a slice thickness of 3.75 mm and a pitch of 1.5. The results
      could be compared with a ventilation-perfusion scan in 48 cases, with a Doppler
      ultrasound examination in 46 cases, and with a venography in 10 cases.
      Furthermore, the image quality of all arterial and venous regions was
      subjectively assessed. RESULTS: In all patients who underwent multi-slice CT the
      pulmonary arteries as well as the veins of the lower half of the body could be
      recorded completely. Regarding the pulmonary arteries the image quality showed
      excellent results for the central and segmental arteries. The region up to the
      3rd division in subsegmental branches could be sufficiently judged. More
      peripherally, a diagnostic assessment was not possible. The image quality of the
      veins was excellent in all sections, except the calf, where a reliable diagnosis
      could not be made. The comparison with the other techniques confirmed the
      superiority of multi-slice CT concerning the central and segmental pulmonary
      arteries and the veins from the popliteal vein to the inferior vena cava. In
      contrast, peripheral pulmonary emboli can be detected more certainly in
      ventilation/perfusion scans. The veins of the calf can be evaluated more reliably
      with venography. CONCLUSION: Multi-slice CT proved to be an outstanding tool in
      the diagnosis of acute pulmonary embolism. The clinically suspected disease and a
      causing venous thrombosis can be detected in a fast and reliable way. At present,
      multi-slice CT is not suitable for the recognition of peripheral emboli. However,
      expected technical developments hold promise for future improvements.

PMID- 11471295
TI  - [Optimizing image reconstruction timing for the RR interval in imaging coronary
      arteries with multi-slice computerized tomography].
AB  - PURPOSE: Multislice spiral CT is a newly developed technology that allows the non
      invasive detection of coronary stenoses and plaques. The acquired raw data are
      reconstructed at a given time point in the RR interval of the heart cycle. Thus,
      determination of this time point is a key factor for picture quality and for
      reliable diagnostic results. This study was performed to investigate the optimal
      time point for reconstruction within the RR interval. MATERIALS AND METHODS: The
      coronary arteries of 13 patients were examined with CT. Raw data were
      reconstructed 250, 350, 450 and 550 ms before the following R wave (absolute
      reverse retrospective ECG gating) for each patient. Data were then analyzed with
      a volume rendering mode on a SIEMENS 3 D-Virtuoso workstation. A total of 91
      segments (segments 1 and 2 of the RCA, segments 5, 6, 7 and proximal and distal
      parts of segment 11) were assessed and image quality was classified. RESULTS:
      Visualization of the left main coronary artery was of a good quality at all time
      points, segments 6 and 7 of the LAD as well as the proximal and distal parts of
      segment 11 of the RCX had the best quality at 450 ms absolute reverse
      retrospective ECG gating. The segments 1 and 2 of the RCA were of best quality
      550% ms absolute reverse to the R peak. CONCLUSIONS: Classification of image
      quality of coronary artery CT scans after retrospectively ECG gated
      reconstruction is highly determined by the time point of reconstruction in the
      heart cycle. The optimization of this time point increases diagnostic accuracy
      and helps to avoid misinterpretation due to image artifacts.

PMID- 11471296
TI  - [Contrast enhanced MR-angiography (CE-MRA): do contrast media with higher T1
      relaxation improve imaging of carotid stenoses?].
AB  - PURPOSE: CE-MRA is a powerful tool for the non-invasive evaluation of carotid
      artery occlusive disease. However, due to certain drawbacks, it has not
      completely replaced DSA. The purpose of this study was to evaluate if Gd-BOPTA, a
      contrast agent with high T1 relaxivity, can increase the diagnostic accuracy of
      CE-MRA. MATERIAL AND METHODS: The CE-MRA examinations of 54 consecutive patients
      were evaluated by two experienced radiologists, independently. The examinations
      of 27 patients were contrasted either with 20 ml Gd-BOPTA or with 20 ml Gd-DTPA.
      The reviewers were blinded to the contrast agent chosen and to the ultrasound
      results. They rated the overall image quality and the degree of the ICA stenoses.
      RESULTS: For the estimation of the degree of the ICA stenoses there was a high
      interrater validity. In comparison to the ultrasound findings, 6 of 50 high
      degree stenoses were underestimated as moderate stenoses. In one of seven
      sonographically occluded vessels, MRA revealed residual patency in the vessel
      lumen. It was not possible to identify the contrast agent that was taken for a
      study. Subjective estimation of the image quality (arterial contrast of the ICA,
      contrast of the other vessels, and general impression) did not significantly
      change with the contrast agent employed. CONCLUSION: The diagnostic accuracy of
      CE-MRA for the evaluation of internal carotid artery stenoses is not improved by
      Gd-BOPTA if identical volumina of contrast media are applied. The potential of
      this contrast agent can be the reduction of the amount of contrast without loss
      of diagnostic information. Further studies are necessary.

PMID- 11471297
TI  - [Automated image analysis of lateral roentgen images of the spine using anatomic
      models].
AB  - PURPOSE: Development of a software for fully automated image analysis of lateral
      lumbar spine X-rays. MATERIAL AND METHOD: Using the concept of active shape
      models, we developed a software that produces a form model of the lumbar spine
      from lateral lumbar spine radiographs and runs an automated image segmentation.
      This model is able to detect lumbar vertebrae automatically after the filtering
      of digitized X-ray images. The model was trained with 20 lateral lumbar spine
      radiographs with no pathological findings before we evaluated the software with
      30 further X-ray images which were sorted by image quality ranging from one
      (best) to three (worst). There were 10 images for each quality. RESULTS: Image
      recognition strongly depended on image quality. In group one 52 and in group two
      51 out of 60 vertebral bodies including the sacrum were recognized, but in group
      three only 18 vertebral bodies were properly identified. CONCLUSION: Fully
      automated and reliable recognition of vertebral bodies from lateral spine
      radiographs using the concept of active shape models is possible. The precision
      of this technique is limited by the superposition of different structures.
      Further improvements are necessary. Therefore standardized image quality and
      enlargement of the training data set are required.

PMID- 11471298
TI  - [A simple method for estimating effective dose in dental CT. Conversion factors
      and calculation examples for a clinical low dose protocol].
AB  - PURPOSE: An easily applicable method to estimate effective dose including in its
      definition the high radiosensitivity of the salivary glands from dental computed
      tomography is presented. Effective doses were calculated for a markedly dose
      reduced dental CT protocol as well as for standard settings. Data are compared
      with effective doses from the literature obtained with other modalities
      frequently used in dental care. METHODS: Conversion factors based on the weighted
      Computed Tomography Dose Index were derived from published data to calculate
      effective dose values for various CT exposure settings. RESULTS: Conversion
      factors determined can be used for clinically used kVp settings and
      prefiltrations. With reduced tube current an effective dose for a CT examination
      of the maxilla of 22 microSv can be achieved, which compares to values typically
      obtained with panoramic radiography (26 microSv). A CT scan of the mandible,
      respectively, gives 123 microSv comparable to a full mouth survey with intraoral
      films (150 microSv). CONCLUSION: For standard CT scan protocols of the mandible,
      effective doses exceed 600 microSv. Hence, low dose protocols for dental CT
      should be considered whenever feasable, especially for paediatric patients. If
      hard tissue diagnoses is performed, the potential of dose reduction is
      significant despite the higher image noise levels as readability is still
      adequate.

PMID- 11471299
TI  - [Body build and radiation exposure in static roentgen studies (I): A contribution
      for determining a national reference dose value. Promoted by the Federal Office
      for Radiation Protection (St.Sch 4163)].
AB  - PURPOSE: To contribute data on radiation exposure in static x-ray procedures and
      to compare them with anthropometric parameters. METHOD: 121 chest x-rays and 100
      lumbar spine examinations were carried out and the dose-area product (DAP)
      measured for each of the projections. Additionally, body height, body weight and
      the sagittal and transversal diameters of the examined regions were recorded.
      Dose measurements were statistically evaluated and the following data determined:
      Frequency distribution, median, 25%- and 75%-percentiles as well as correlations
      with sex, body weight and diameters. RESULTS: Median DAP was 13 (men: 16; women:
      11) resp. 50 (62; 37) cGycm2 with pa resp lateral chest x-ray. Values were
      closely correlated with body weight (r = 0.704/0.659) and diameter of the chest
      (r = 0.657/0.579). Median DAP was 175 (239; 126) resp 531 (670; 361) cGycm2 with
      ap resp lateral lumbar spine examinations. Values were closely correlated with
      body weight (r = 0.678/0.666) and diameter of the abdomen (r = 0.664/0.658).
      CONCLUSIONS: DAP of chest x-rays and lumbar spine examinations is strongly
      influenced by the constitution of the patients. Men are nearly twice as largely
      exposed to radiation as women.

PMID- 11471300
TI  - [Once upon a time, did acute renal failure exist in Spanish nephrology?].

PMID- 11471301
TI  - [Can one do research in an INSALUD hospital?].

PMID- 11471302
TI  - [Toward individualized immunosuppression].

PMID- 11471303
TI  - [Guanylate cyclases: physiological processes mediated by cyclic GMP].

PMID- 11471304
TI  - [Control of arterial pressure in diabetic nephropathy].

PMID- 11471305
TI  - [Report of dialysis and transplantation from the Spanish Nephrology Society and
      the Autonomous Registries for the year 1999].

PMID- 11471306
TI  - Quantitative analysis of the interstitial mast cells in idiopathic
      mesangiocapillary glomerulonephritis type I.
AB  - Fourteen renal biopsy specimens from patients with mesangiocapillary
      glomerulonephritis type I (MCGN-I) for whom both light and electron microscopy as
      well as immunofluorescence microscopy and full clinical data were available were
      examined quantitatively. As a control 10 biopsy specimens of kidneys removed
      because of trauma were used. Morphometric investigations were performed by means
      of a computer image analysis system to evaluate whether mast cells have a role in
      tubulointerstitial fibrosis in MCGN-I and to examine the relationship between
      mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression as
      well as interstitial infiltrates. The morphometric study revealed that the mean
      values of the interstitial tryptase positive cells, expression of alpha-SMA,
      interstitial volume, CD 68+, CD 45RB+, CD 43+ and CD 20+ cells were significantly
      increased in MCGN-I patients in comparison with control group. In MCGN-I group
      there were significant positive correlations between interstitial tryptase
      positive cells and interstitial expression of alpha-SMA, interstitial volume,
      serum creatinine as well as CD 43+ and CD 68+ cells. The correlations between
      interstitial tryptase positive cells and CD 45+, as well as CD 20+ cells did not
      reach statistical significance. In conclusion, our findings demonstrate that mast
      cells are one of the constitutive cell types in the interstitium in MCGN-I.
      Additionally, significant positive correlations between interstitial mast cell
      count and relative interstitial volume as well as serum creatinine concentration
      suggest the role of these cells in the development of interstitial fibrosis which
      may contribute to the renal deterioration in patients with MCGN-I.

PMID- 11471307
TI  - [Analysis of the survival of permanent vascular access ports].
AB  - Complications arising from vascular access are major causes of morbidity in
      patients on renal replacement therapy. They contribute to frustration of health
      care providers and to high medical cost. To prevent failures in the future it
      will be helpful to identify the factors that are related to vascular access,
      malfunction. In a retrospective analysis we analysed the types, duration and
      primary patency rate of 1,033 permanent vascular access in 544 consecutive
      patients established during a 13-year period in a tertiary care hospital. Patient
      characteristics, incidence and risk factors related to vascular access failure
      were registered. In addition vascular access outcomes in patients who started
      haemodialysis with a catheter and in whom initial vascular access failure
      occurred were analysed separately. Forty-five per cent of patients required a
      central catheter at the start of HD, but 92% of them were being dialysed with an
      a-v fistula at the last observation. The total number of complications was 0.24
      episodes per patient per year at risk, and the rate of thrombosis 0.1. A total of
      52% of patients were dialysed throughout the observation period with their
      initial a-v fistula; 9.3% had more than three episodes of vascular access
      failure. The radiocephalic a-v fistula was the access with the best median
      duration, exceeding 7 years, but also the type that had the highest initial
      failure rate, i.e. 25% of patients and 13% of events. The brachiocephalic a-v
      fistula was the second most frequent type of vascular access, with a median
      duration of function of 3.6 years, in contrast the humerobasilar a-v fistula,
      lasted on average over 5 years. Average patency of the different types of grafts
      did not exceed 1 year, with the exception of the autologous saphenous graft with
      a median duration of function of 1.4 years. Patients with glomerulonephritis had
      the best function rates for their access, the median duration exceeding the
      duration of the study, whereas in half of diabetic patients it was less than 1
      year. The duration of patency of the vascular access was twice as long in
      patients below age 65 years and in elderly males compared to elderly females.
      Patients who start HD with a catheter, as well as those with initial vascular
      access failure, have a higher rate of access failure in the subsequent course on
      renal replacement therapy. In conclusion, the radiocephalic and the
      brachiocephalic a-v fistula are the two types of vascular access with the longest
      duration of function, although a high rate of initial failure is seen with the
      radiocephalic a-v fistula. Age, female gender, presence of diabetic nephropathy,
      start of dialysis with a catheter, and failure to wait for initial maturation of
      vascular access are risk factors, and account for the majority of vascular access
      failure during renal replacement therapy.

PMID- 11471308
TI  - [Predictors of early death during dialysis].
AB  - The mortality among end-stage renal failure (ESRF) patients undergoing renal
      replacement therapy (RRT) remains high. An important proportion of these patients
      die shortly after the initiation of RRT. The present study aims to determine the
      best predictors for the early mortality in a group of 140 ESRF patients who
      initiated RRT between october 96 and december 99. The mean age of the study group
      was 61 +/- 13 years, and the mean follow-up time was 20 +/- 12 months. Diabetic
      nephropathy was the most prevalent etiology of renal failure (30%). The following
      data, collected immediately before the initiation of RRT, were included as
      independent variables: demographic and clinical characteristics, including the
      nutritional status established by the Subjective Global Assessment (SGA), follow
      up time in the predialysis clinic (less or longer than 3 months), EPO therapy,
      vascular access, renal function (creatinine and urea clearances, and Kt/V urea),
      hematological and biochemical data including serum albumin, bicarbonate,
      transferrin, PTH and C-Reactive protein, as well as the protein catabolic rate
      and the percent of lean body mass normalized for ideal body weight, calculated
      from the 24 h total urine excretion of nitrogen and creatinine. The Cox
      proportional hazard regression model, stratified for an age over or less than 65
      year, was utilized to determine the best predictors for the mortality during the
      study period. Sixty percent of patients had at least one comorbid condition, and
      35% had cardiovascular diseases. Mild-moderate or severe malnutrition was
      observed in 48% of patients. The creatinine clearance and Kt/V urea before the
      initiation of RRT were: 9.50 +/- 2.64 ml/min/1.73 m2 and 1.47 +/- 0.44,
      respectively. Forty-one patients died during the study period (annual death rate:
      17%). The best predictor of mortality was the nutritional status assessed by the
      SGA (OR: 2.32, IC 95% 1.54-3.48, p < 0.0001). In a second analysis in which the
      SGA was removed from the model, the previous history of cardiovascular diseases
      (OR: 2.07, CI 95%: 1.06-4.06, p = 0.032), and the percent of lean body mass/ideal
      weight (OR: 0.96; IC 95%: 0.93-0.99; p = 0.042), proved to be the best predictor
      of mortality. In conclusion, nutritional indices prior to the initiation of RRT,
      and the previous history of cardiovascular diseases were the best predictors of
      the early mortality in this unselected population on dialysis. Because
      nutritional status appeared to be a marker of the severity of the comorbid
      conditions, a better control of the number and severity of these comorbid
      conditions may be the best way for reducing the mortality in patients on RRT.

PMID- 11471309
TI  - [Costs of chronic dialysis in a public hospital: myths and realities].
AB  - In this study regular dialysis treatment costs during 1998 and 1999 in a public
      hospital, which is responsible for a population of 178,000, has been analysed.
      Hemodialysis (HD) and peritoneal dialysis (PD) costs have been differentiated and
      compared with those of external providers. The best technical and productive
      efficiency of both treatments have been estimated by analyzing the "treatment
      cost/human resources of the community utilized" relationship. The HD treatment
      costs per patient per year were 20,343 and 18,871 euros in 1988 and 1,999,
      respectively, lower than the costs reported in other studies. In 1999 these costs
      were similar to those of external providers and lower than the PD treatment costs
      (23,295 euros). HD retains its advantage even after costs of erythropoietin,
      hospital admissions and transport are included. In the hospital studied, the best
      technical efficiency in HD would be reached with 64 patients on treatment (17,851
      euros per patient per year) and in PD with 48 patients (21,167 euros per patient
      per year). If we take into account our population characteristics and consider a
      patient distribution of 70% on HD and 30% on PD, the best productive efficiency
      would be reached with 56 patients on HD (17,916 euros per patient per year) and
      24 patients on PD (21,813 euros per patient per year). HD confers the greatest
      economic and social benefits on the population supplied by the hospital since it
      provides the community with more jobs than PD in relation to treatment costs
      while the two yield the same clinical results. In conclusion, HD in a public
      hospital, at least in our environment, may be efficient and competitive with HD
      from external providers and it may be more efficient and provide a bigger
      economic and social profit for the population serviced by the hospital than PD,
      at least while the current supply systems for this treatment in our country are
      maintained.

PMID- 11471310
TI  - [Changes in renal function in renal transplantation. Predictive factors for
      functional deterioration].
AB  - Renal transplants may undergo changes secondary to the decrease of the renal
      mass, the effects of rejection, and various other risk factors that contribute to
      the progression of renal insufficiency. We have performed a prospective study of
      285 cadaveric renal transplants recipients, that were receiving various
      maintenance immunosuppressives regimens, to study the evolution of their renal
      function and to evaluate the influence of various factors in the progression of
      renal insufficiency. All variables were analysed in a regression model of
      multivariate analysis. We found a progressive increase of the serum creatinine in
      the studied population. The mean initial creatinine was 1.70 +/- 0.84 mg/dl and
      final creatinine in the study 2.17 +/- 2.06 mg/dl, difference statistically
      significant (p = 0.000). We calculated the increase of creatinine in each
      patient. We observed that 113 patients (42.2%), had stable serum creatinine but
      the remaining 155 patients (57.8%) had a mean increase of 0.04 +/- 0.8
      mg/dl/month. We analysed the patients according to various variables. Although in
      most the final creatinine is significantly greater than the initial, this
      increase of creatinine level was not present in patients with delayed graft
      function, in patients with no acute rejection, in the extreme age groups, in the
      grafts from younger donors and in those patients without initial proteinuria. The
      patients transplanted from younger donor had the best renal function, without any
      decrease in their function during the study. The advanced age of the donor has a
      great negative impact in the evolution of the renal transplant. According to our
      study, proteinuria and its quantity is a major predictor of progressive renal
      insufficiency. The multivariate analysis confirms that the age of the donor and
      initial proteinuria predict decrease of renal function. It is important to
      identify the factors that they could predict a greater progression to the failure
      of the graft. We have the possibility of acting on them, establishing
      immunosuppressive strategies that reduce the deleterious effects of the
      calcineurin inhibitors in the recipients of grafts from older donors' and to
      encourage the use of drugs which reduce proteinuria.

PMID- 11471311
TI  - [Reversible posterior leukoencephalopathy, severe hypertension, and cocaine
      abuse].
AB  - Reversible posterior leukoencephalopathy syndrome is a brain disorder
      characterized by headache, nausea, vomiting, visual disturbance, depressed level
      of consciousness, convulsions and occasionally focal neurologic deficits. It is
      commonly associated with malignant hypertension, toxemia of pregnancy or the use
      of immunosuppressive agents. Early diagnosis and specific treatment is essential.
      We report a case of reversible posterior leukoencephalopathy in the context of a
      hypertensive crisis in an habitual cocaine sniffer. Reversible posterior
      leukoencephalopathy must be suspected in every patient with hypertensive crisis
      and compatible clinic manifestation. Neuroimaging studies show characteristic
      features which confirm the diagnosis.

PMID- 11471312
TI  - [Rhabdomyolysis and acute renal failure secondary to statins].
AB  - Statins are competitive inhibitors of hydroxy-methyl-glutaryl coenzyme A (HMG
      CoA) reductase and are the most commonly used drugs to treat hyperlipidaemia.
      Muscle toxicity is an adverse effect reported with a low incidence and rarely
      associated with acute renal failure due to rhabdomyolysis. We describe two
      patients with chronic renal failure treated with pravastatin and simvastatin who
      suffered rhabdomyolysis and acute renal failure. One patient started pravastatin
      several days after cessation of bezafibrate and developed acute renal failure
      without needing dialysis. The other was treated with simvastatin three years ago
      and suffered rhabdomyolysis when renal function was impaired after indomethacin
      was prescribed for backache. He needed hemodialysis because of acute cardiac
      failure and died from a respiratory infection while on mechanical ventilation.
      Myopathy was reversible in both patients. We recommend starting statins with the
      lower doses in chronic renal failure and monitoring muscle enzymes when renal
      function changes or when new drugs with potential interactions are prescribed.

PMID- 11471313
TI  - [Ileocecal tuberculosis during hemodialysis simulating carcinoma of the colon].
AB  - Extrapulmonary tuberculosis is more frequent in hemodialysis patients than in the
      general population but intestinal localization is an unusual presentation of this
      infectious disease. We report a 60 year old patient on regular hemodialysis with
      intestinal tuberculosis masquerading as colon cancer. The patient presented with
      rectal bleeding, abdominal pain and fever and the radiological findings were
      compatible with ileocecal carcinoma. After surgery histological examination
      showed non-caseating granulomas but mycobacterial culture was not available. We
      performed a colonoscopy and obtained a biopsy of colonic mucosa for culture and
      other analyses. We identified acid-fast bacilli with Ziehl-Neelsen staining of
      formaldehyde preserved, paraffin-embedded tissue from the hemicolectomy and the
      colonic mucosal biopsy. Treatment with isoniazid, rifampicin and pyrazinamide for
      nine months was successful and well tolerated. Intestinal tuberculosis is a rare
      entity that we must keep in mind in a patient with abdominal pain, unexplained
      fever, digestive bleeding and particularly with a positive tuberculin reaction.
      When culture is not possible we can obtain intestinal samples by colonoscopy and
      use appropriate staining of paraffin-embedded tissues.

PMID- 11471314
TI  - [Bilateral hydronephrosis caused by a "fungus ball"].

PMID- 11471315
TI  - [Pre-dialysis vascular access. Does the evidence justify it?].

PMID- 11471316
TI  - [Acute renal insufficiency and interstitial nephritis caused by rifampicin. A
      comment on this subject].

PMID- 11471317
TI  - [Ischemic colitis: an underdiagnosed disease in hemodialysis].

PMID- 11471318
TI  - [Effects of aminobisphosphonates on the superior digestive tract mucosa].

PMID- 11471319
TI  - [Esophagitis associated with use of alendronate in 5 postmenopausic patients].
AB  - The bisphosphonate, alendronate sodium (e.g. Fosamax) is a bone resorption
      inhibitor used to treat postmenopausal osteoporotic women and osseous Paget's
      disease. Esophagitis is one of the adverse effects (AE) associated to its use.
      Five (5) patients with alendronate-associated esophagitis assisted in the
      Gastroenterologic Center, Rosario, Argentina, between October 1996 and December
      1999 are described. The aim is to correlate the clinical, endoscopic and
      histopathological findings in 5 women (ages 57-71) complaining for upper
      digestive symptoms (dysphagia, epigastralgia, retrosternal pain.). All had
      osteoporosis treated with alendronate 10 mg/day and received detailed
      instructions about how to take the medication. The time from the beginning of
      alendronate intake and the appearance of the symptoms was elapsed 30, 35, 67, 85
      and 90 days. The esophagitis was graded according to the Savary-Miller
      Classification. The videoscopy disclosed esophagitis of III and IV grades. Three
      patients had also antral and antroduodenal lesions, one of them associated to
      Helicobacter Pylori. Anatomopathologic findings confirm esophagitis and esophagic
      ulceration. Some authors claim that bisphosphonates as a new class of gastrotoxic
      drugs with AE similar to aspirin. Even when it is administrated according to the
      instructions of the manufacturers it should be used with caution. Our
      contribution emphasize the importance of this AE and suggest measures to diminish
      or suppress them, and take into consideration those patients who are taking
      aspirin. With alendronate, as well as with other potentially corrosive agents, is
      very important to take in mind the measures to prevent AE.

PMID- 11471320
TI  - [Colonic cancer: an enemy in retreat?].
AB  - Argentina and Uruguay are countries with high mortality rates for colorectal
      cancer. In the Province of Santa Fe, colorectal cancer ranks as third when
      considering cancer as the cause of death. The aim in this study was to compare
      the mortality rates for colorectal cancer in the Province for a 10 year period.
      The mortality rates for 1985-1987 and 1995-1997 were 17.2% an 19.1% respectively.
      There was no significant difference with the mortality rates during that decade
      our study encompasses.

PMID- 11471321
TI  - [Activation of K-ras and c-erbB-2 protooncogenes in human colonic
      adenocarcinomas].
AB  - Although data on genetic alterations leading to development of colorectal cancer
      are abundant, no specific genetic alteration has been demonstrated for each class
      of tumor. The colorectal cancer phenotype is originated from an accumulation of
      different genetic alterations. The nature of these alterations, their order of
      appearance, and their associations vary greatly from one tumor to another,
      suggesting that the concept of a unique model of carcinogenesis is not applicable
      to these tumors. The aim of the present work was to study the association between
      K-ras and c-erbB-2 mutations and different clinicopathological variables in fifty
      four samples from adenocarcinomas of the colon. The detection of K-ras activation
      was performed by specific enriched PCR. The genomic differential polymerase chain
      reaction with the single copy reference gene was employed for the detection of c
      erbB-2 gene amplification. K-ras mutations were detected in 16 cases (29.63%) and
      c-erbB-2 amplifications in 1 sample (1.85%). Statistical analysis showed a
      significant association between K-ras codon 12 mutation frequency and Duke's
      stage B (p < 0.05). On the other hand, there was no association in relation to
      the other studied parameters. These results could indicate the occurrence of K
      ras activation in early stages of the disease.

PMID- 11471322
TI  - Ascites due to hypothyroidism in a patient with alcoholic cirrhosis.
AB  - Myxedema is the cause of ascites in less than 1% of new-onset ascites cases,
      where as only 4% of patients with hypothyroidism present ascites. When ascites is
      the first manifestation of thyroid insufficiency, there is usually a delay in
      diagnosis. We report here a case of myxedema ascites occurring in a patient with
      alcoholic cirrhosis, that was first thought to be the cause of the ascites, and
      review the features of 48 cases previously reported. Some clinic and analytical
      findings that have been commonly reported, are the long duration of the ascites
      before diagnosis, the prompt response (with resolution of ascites) to thyroid
      replacement treatment, a high total protein concentration in ascites fluid, white
      moderate white blood cell counts and a lymphocyte predominance. Serum-ascites
      albumin gradient has been postulated to be high in myxedema ascites, but we
      believe this has been studied in too few cases thus far, to be conclusive.

PMID- 11471323
TI  - [Liver hyperdensity during arterial phase on CT exams].
AB  - The use of helical CT, infusing pump and non-ionic contrast media has enabled the
      evaluation of different hepatic circulatory phases during contrast injection.
      Starting the acquisition of scans 20 to 30 seconds after the injection at a rate
      of 3 to 4 ml/sec the arterial enhancing of the liver is depicted. THROMBOSIS OR
      COMPRESSION OF THE PORTAL VEIN: Hypervascular triangle-shaped was with peripheral
      base can be seen, secondary to the increased arterial flow to compensate for the
      diminished portal flow. ARTERIOPORTAL SHUNTS: This condition can be caused by
      tumors such hepatocellular adenocarcinomas and hemangiomas, trauma,
      interventional procedures, cirrhosis, AVMs and surgery. INFLAMMATORY LESIONS:
      Hypervascular areas can be seen during the arterial phase in abscesses or
      cholecystitis, returning to their normal condition in the arterial phase.
      ANATOMIC VARIANTS: Third veins coming from the periphery (capsular veins,
      accessory cystic vein and an aberrant gastric vein) supply enhanced blood earlier
      than the portal circulation. OTHER CAUSES: In liver cirrhosis diffuse
      hyperattenuated areas can be seen during the arterial circulation. In right-sided
      heart failure, pericardial disease and Budd-Chiari Syndrome, "mosaic areas" can
      also be noted. In other patients these perfusion disorders were considered
      unknown. TUMORS: The well-differentiated hepatocellular carcinoma is a lesion
      with a predominant arterial blood supply, thus appearing in general hyperdense in
      this phase. Hemangiomas may appear as highly hyperdense lesions in the arterial
      phase and can be misinterpreted as HCC if smaller than 2 cm. (30% of cases).
      Focal nodular hyperplasia is a benign lesion (vascular malformation associated
      with focal nodules of hepatocellular hyperplasia) with increased arterial blood
      supply. Hepatic adenomas show an important hypervascularity during the arterial
      phase and, if large, they may present a small central scar and or capsule. Low or
      high-grade dysplastic nodules can sometimes be seen as hypervascular areas during
      the arterial phase. Although most metastasis are depicted as hypodense lesions
      sometimes they can show arterial hypervascularity such as carcinoid and
      pancreatic islet cell metastasis.

PMID- 11471324
TI  - [History of medicine: the esophagology in Argentina].
AB  - The author reviews the history of the people, their contributions, and the facts
      related to the development of esophageal pathology knowledge in Argentina.

PMID- 11471325
TI  - Optimum use of the microbiology laboratory in testing for stool pathogens and
      antimicrobial susceptibility testing (AMST).

PMID- 11471326
TI  - DVT prophylaxis: a lost art?

PMID- 11471327
TI  - Quality improvement for stroke.

PMID- 11471328
TI  - DDAVP-associated hyponatremia.
AB  - More than 250,000 patients with nocturnal enuresis have been treated with DDAVP
      in the United States since 1989. It adequately controls nocturnal enuresis in
      over half of patients with significant improvement in their quality of life.
      Although the overall incidence of adverse effects associated with treatment of
      nocturnal enuresis with DDAVP is low, it is not a benign drug particularly when
      used in patients at extreme of age. A review of the literature and the present
      case demonstrate that the potential risk factors for hyponatremia following
      administration of DDAVP include hepatic disease, surgery, stress, pain, renal
      disorder, excessive fluid intake, and increased dose of DDAVP. Potentially
      serious side effects of DDAVP administration such as hyponatremia and seizure may
      be prevented by close monitoring of serum electrolytes, urine output, as well as
      fluid restriction and avoidance of solutions with low-sodium content.

PMID- 11471329
TI  - Toxic playgrounds.

PMID- 11471330
TI  - The artificial heart, revisited.

PMID- 11471331
TI  - Is transference the 'total situation'?
AB  - This paper examines through the detailed explication of analytic material the
      author's experience of a psychoanalytic and a Jungian way of understanding the
      interactions between him and his patient. This comparative approach considers
      where the differences lie with respect to timing and content of interpretations
      and where the differences are essentially tactical rather than theoretical.

PMID- 11471332
TI  - Confidentiality and paradox: the location of ethical space.
AB  - Implicit in Jung's alchemical metaphor of the vas bene clausum is the idea of an
      analytic frame with a space inside it for something vital, a relationship between
      two selves, to develop. For this to happen, analysts must respect their patients'
      rights to confidentiality. The paper explores the analyst's state of mind and the
      intrapsychic processes that are constellated when struggling with ethical
      dilemmas about issues of confidentiality in analytic work. The author suggests
      that at times when analysts consider breaking confidentiality, there is often a
      disturbing inner conflict between their moral principles (codes of ethics) and
      their internal personal ethical attitude. At these difficult moments, the
      mutuality of the work and the vas bene clausum can be significantly disrupted.
      The analyst tries to find a third position, a mental and emotional ethical space
      where the subjective and the objective, the ethical and the unethical can become
      more companionable bedfellows.

PMID- 11471333
TI  - Origins of the ethical attitude.
AB  - This paper seeks to explore the genesis of the capacity for an ethical attitude,
      personally and professionally. As analysts working in intimate clinical settings,
      ethics is at the foundation of our professional lives, as it is at the foundation
      of our humanity and what it is we struggle towards in our own personal
      development. The ethical attitude presupposes special responsibilities that we
      choose to adopt in relation to another. Thus, a parallel situation pertains
      between caregiver and child and between analyst and patient: they are not equal
      partners, but nevertheless are in a situation of mutuality, shared subjectivity,
      and reciprocal influence. The basic premise of this paper is that the analytic
      attitude is an ethical attitude, and that the ethical attitude is a developmental
      achievement, and as such it may reach beyond the depressive position.

PMID- 11471335
TI  - Reports on the VIIIth International Meeting of the International Association for
      the History of Psychoanalysis (IAHP). 20-22 July 2000 Versailles, France.

PMID- 11471334
TI  - The Martin Buber-Carl Jung disputations: protecting the sacred in the battle for
      the boundaries of analytical psychology.
AB  - The Martin Buber-C.G. Jung disputations rather than the Freud-Jung split or
      Samuels's post-Jungian categories is considered the more significant paradigm for
      understanding the conflicts erupting within the Jungian community surrounding
      clinical practice and candidate training. Looking through the lens of the Freud
      Jung split keeps the conflicts focused on the theoretical and technical
      differences concerning such concepts as object-relations, transference
      countertransference, neutrality, clinical boundaries. The Buber-Jung disputations
      move the discussion into a different and more foundational arena, namely the
      vertical and horizontal psychological considerations of the experience of the
      Sacred and how that dimension is supported or thwarted in clinical practice and
      candidate training by the respective allegiances of the 'warriors' in the 'Holy
      Wars'. Experiencing the texture of the Buber-Jung disputations as well as
      grappling with their content suggests that a more dialogical approach to actual
      clinical material may be a more fruitful way to understand the work of analysis
      and the business of candidate training.

PMID- 11471336
TI  - Too much knife, not enough handle. A reply to von Raffay's critical attack on the
      anima concept.

PMID- 11471337
TI  - Introduction. The nose. The gateway to the lungs.

PMID- 11471338
TI  - Wegener's granulomatosis and the Churg-Strauss syndrome.

PMID- 11471339
TI  - Allergic rhinitis/asthma interrelationships.

PMID- 11471340
TI  - Nasal-pulmonary relations in allergic fungal sinusitis and allergic
      bronchopulmonary aspergillosis.

PMID- 11471341
TI  - Sinus disease in cystic fibrosis.

PMID- 11471342
TI  - Dyskinetic cilia and Kartagener's syndrome. Bronchiectasis with a twist.

PMID- 11471344
TI  - Technical developments in cardiac MRI: 2000 update.
AB  - In recent years, the technological developments in MRI have made it possible to
      perform routine cardiovascular imaging with MR. The availability of a
      vectorcardiogram, real time interactive scanning, SENSE and optimized protocols
      (balanced FFE) have made it possible to evaluate wall motion, perfusion and
      viability at rest and under stress. All vessels can be visualized, including the
      coronary arteries. In the near future, MRI will be capable of distinguishing
      between calcified and lipid plaque, and will even allow interventional
      applications.

PMID- 11471343
TI  - Aspirin-induced asthma.

PMID- 11471345
TI  - Technical developments in cardiac CT: 2000 update.
AB  - Preliminary results of the new generation CT scanners in the study of the heart
      and coronary arteries, are reported, after an overview of basic anatomy,
      physiology and main technical problems. Comparison is made with the other
      conventional procedures. The clinical validation of cardiac CT is under way while
      preliminary results are very encouraging. However, for cardiac CT to become an
      examination of first choice in the study of the heart and coronary arteries,
      spatial resolution should be improved and acquisitions of 15 cm volume with less
      than 15 sec breath-hold should be feasible. The improvement in cardiac
      synchronization and temporal resolution will allow a kynetic systolic as well as
      diastolic study. This is going to be possible with the new generation CT scanners
      able of 16 or 32 sections per second.

PMID- 11471346
TI  - MRI assessment of ventricular function.
AB  - Cine-MRI is a robust non invasive technique able to assess regional and global
      systolic function of both ventricles. Conventinal cine-MRI was used for LV global
      function parameters both on horizontal long axis and vertical long axis, applying
      area-length methods, as in echocardiography. Recent developments of segmented k
      space techniques allowed breath-held cine-MRI, making possible a rapid
      acquisition of the entire ventricles, both left and right. Using the Simpson's
      rule volumes are estimated with high accuracy, without any geometrical
      assumption; this method is considered gold standard for global function
      assessment. Regional function is studied by cine-MRI both qualitatively and
      quantitatively, as it represents the best technique in defining endo- and epi
      cardial borders. The ability of quantify wall thickness and wall thickening makes
      cine-MRI highly suitable for stress-imaging, both in ischemia detection and
      viability assessment. Tagging is a novel technique, able to assess the complex
      mechanism of myocardial contraction and to quantify myocardial strain. Finally
      MRI is also able to assess diastolic function with phase velocity mapping.

PMID- 11471347
TI  - Myocardial contrast echocardiography: a new tool in the noninvasive assessment of
      perfusion.
AB  - Although the ability to visualize the microvascular circulation by injection of
      microbubbles has been recognized for over 30 years, only recently the
      considerable progress in both ultrasound techniques and new contrast media has
      made myocardial contrast echocardiography a reliable, noninvasive method for the
      assessment of regional myocardial perfusion. Several clinical studies have
      validated this technique for the identification of resting myocardial perfusion
      defects after myocardial infarction and the detection of no-reflow in ischemia
      reperfusion model. In addition, preliminary studies have shown the ability of
      this method to recognize regional myocardial ischemia during pharmacological
      stress tests in known or suspected coronary artery disease. Finally, in the
      experimental setting, the estimation of different degrees of severity of coronary
      artery stenosis has been proposed using the quantitative assessment of myocardial
      perfusion by time-intensity curves. Although to date some unresolved questions
      hinder the routine clinical application of this novel noninvasive technique,
      myocardial contrast echocardiography is close to providing significant advances
      in the ultimate goal of any cardiac imaging technique, i.e. the simultaneous
      assessment of both perfusion and function.

PMID- 11471348
TI  - Magnetic resonance first-pass perfusion imaging: overview and perspectives.
AB  - The data from clinical studies with quantitative MR first-pass perfusion imaging
      suggests that this technique outperforms SPECT--widely available clinical imaging
      tool--in sensitivity and specificity. Moreover, MRFP imaging may be combined with
      the assessment of global and segmental function of the heart and regional wall
      thickening, and in addition, performed with pharmacological stress agents. The
      inter- and intra-observer reproducibility of quantitative MRFP is comparable with
      clinically used nuclear medicine techniques. MRFP measurements can discern
      collateral myocardium and are able to identify small changes in myocardial blood
      flow and myocardial perfusion reserve (the ratio of stress blood flow over
      resting). MRFP imaging has been mainly used in context of coronary artery disease
      but many other exciting areas in clinical cardiology are awaiting of new insights
      that can be accomplished with this technique. Trials are needed to obtain the
      approval of the contrast agent (Gd-DTPA) and perfusion sequences by the Food and
      Drug Administration and to establish reimbursement procedures with the third
      party insurance companies and health maintenance organizations.

PMID- 11471349
TI  - MR coronary angiography: 2001 update.
AB  - Cardiovascular magnetic resonance (CMR) has developed multiple techniques that
      have made it possible to overcome the substantial difficulties in imaging
      coronary arteries. Tortuous small coronary arteries are imaged in 3D-volume data
      sets. Cardiac motion is reduced by diastolic gating with ultra-fast sequences.
      Respiration is suppressed by breath-holding or respiratory gating. Signal-to
      noise can be increased with contrast agents. In clinical trials CMR has been
      successfully used to assess coronary artery stenoses, coronary artery bypass
      grafts, and anomalous coronary arteries. Recent developments in steady state
      imaging, volume selective imaging with tracking, parallel imaging techniques,
      vessel wall imaging, and intravascular contrast agents may soon enable CMR of the
      coronary arteries to become an effective and widespread clinical tool.

PMID- 11471350
TI  - Cardiovascular applications of magnetic resonance flow measurement.
AB  - Magnetic resonance flow measurement is a technique that can be applied in many
      areas of cardiovascular diagnosis. It is unique in its ability to acquire
      comprehensive velocity and spatial information, which makes it an accurate
      quantitative tool. In the evaluation of valvular heart disease and congenital
      heart disease, use of MR flow imaging is well established. In the assessment of
      coronary artery disease, MR quantification of coronary flow, in conjunction with
      other MR techniques, makes MR imaging a highly versatile diagnostic imaging
      modality. This article will review the clinical applications of MR flow
      measurement, as well as cover some of the basic physical principles underlying
      the technique, and the associated technical limitations.

PMID- 11471351
TI  - Cardiac MR spectroscopy in the new millennium.
AB  - Spectroscopy is close to becoming an integral part of the clinical MR examination
      to achieve a complete morphological, functional, and metabolic evaluation of the
      human heart. 31P-NMR spectroscopy is used to noninvasively assess human
      myocardial energy metabolism. Abnormalities in the phosphocreatine (PCr) to ATP
      ratio are observed in ischemic heart disease, heart failure, transplanted hearts,
      and hypertrophic cardiomyopathy. NMR spectroscopy 31P spectra obtained at rest,
      during exercise or pharmacological stress allow the observation of the earliest
      metabolic responses of myocardial ischemia. 1 spectroscopy can evaluate the
      concentration of intracellular creatine and myocardial lipids as a means of
      evaluating myocardial viability. The increase in total 23Na in ischemic tissue
      provides information about the extent and location of viable tissue. Higher
      magnetic fields, gradient strength, and technological advances in pulse sequence
      and localization will result in better spatial and temporal resolution improving
      the clinical utility of the technique.

PMID- 11471352
TI  - Prescription for recovery.

PMID- 11471353
TI  - More power to whom?

PMID- 11471354
TI  - alt.medicine.

PMID- 11471355
TI  - There's still gold in them thar pills.

PMID- 11471356
TI  - Can Merck stand alone?

PMID- 11471357
TI  - A new prescription for your portfolio.

PMID- 11471358
TI  - 'The future of cancer treatment'.

PMID- 11471359
TI  - [Critical reflections on innovation, therapeutic progress and economics of
      health].
AB  - Innovation should not be likened to progress and cost, true innovation should be
      clearly distinguished from false, novelty for novelty's sake should be avoided,
      and medicoeconomic evaluations should be interpreted with caution as they are
      often too precocious and overfavourable. It seems preferable (taking into account
      examples of statins, anti-Cox 2 NSAIDs, antiTNFs, recombinants...) that
      therapeutic innovation, as concerns both the prescriber and the evaluator, should
      give rise to critical reflection rather than to blind enthusiasm and scientistic
      belief. Delayed use, focusing on real or potential dangers, can be as deleterious
      for our patients' health as precipitate or generalized use while only considering
      increased efficacy. Innovation is extremely desirable, particularly when it seems
      to correspond to a health requirement of prior concern. However, it should be
      evaluated with a cool head, without prejudice, and even with a hint of scepticism
      to act as a counterbalance. It should be used with discernment, without improper
      extrapolation to patients for whom it is not necessary. Careful assessment of the
      sanitary and economic consequences of therapeutic innovation--which constitute a
      source of expenditure or economy--should be a permanent concern of health
      authorities. They must be evaluated using reliable and partly independent data
      from firms and paying agencies.

PMID- 11471360
TI  - [Progress in therapy, innovations and economics of health].

PMID- 11471361
TI  - [Treatment of severe arterial hypertension: cost of drug prescriptions in
      accordance with ANAES guidelines].
AB  - French national health insurance has carried out two nationwide surveys as part
      of its programme intended to improve the care given to patients with
      hypertension, focusing on affiliates diagnosed with severe hypertension entitled
      to exemption from co-payments (patients are reimbursed 100 per cent for all care
      related to the corresponding disorder). The objective was to measure the
      difference between observed care and the quality of care delineated in the
      guidelines (1997) elaborated by the National Agency for Healthcare Accreditation
      and Evaluation (ANAES). The before and after comparison was designed to determine
      whether actual care is in accordance with the guideline's standards. The initial
      survey took place from 31 May to 12 November 1999 over the entire French
      territory (metropolitan and overseas departments) and concerned a representative
      sample of patients whose ages ranged from 20 to 80 years at the time they
      qualified for exemption from co-payments for severe hypertension. The method used
      for comparison involved the calculation of a number of different evaluation
      parameters, the principal one being blood pressure control, using the systolic
      (PAS) and diastolic (PAD) pressures reported by attending physicians. Other
      evaluation parameters included the quality of the therapeutic strategy utilized.
      A total of 10,665 patients were enrolled in the survey by using information
      gathered from 8377 practicing physicians. Extrapolated to the entire population
      in 1999, the results can be applied to 50,383 patients. The average age was 63
      years and the patients had been treated for hypertension for an average of 9
      years. In addition to severe hypertension, 64 per cent of the patients had other
      significant high-risk factors for cardiovascular disease: 44 per cent had
      dyslipidemia, 28 per cent had diabetes mellitus, 15 per cent were smokers. In 41
      per cent of cases, the patients' blood pressures were well controlled (systolic
      and diastolic pressures below 140/90 mmHg or, for patients older than 60 years
      with only isolated systolic hypertension, systolic pressure equal to or lower
      than 160 mmHg); in 12 per cent of cases the patients' blood pressures were equal
      to the limit values; in 47 per cent of cases blood pressure was poorly
      controlled. Diabetics had poorly controlled blood pressure in 85 per cent of
      cases (systolic or diastolic pressures greater than 130/85 mmHg) and, similarly,
      94 per cent of the patients who were in renal failure were poorly controlled
      (systolic or diastolic pressures greater than 125/75 mmHg). Preferential
      prescription with a particular therapeutic class, because of an existing
      comorbidity, was found in 68 per cent of patients whereas potentially
      contraindicated therapeutic classes were prescribed in 27 per cent. The daily
      cost of anti-hypertensive drug therapy was estimated at 8.05 francs per day per
      patient. Extrapolated to the study population in 1999, this represents 148.1
      million francs. Less than 1 per cent of this observed cost (1.1 million francs)
      was economized by prescribing less expensive, alternative drug specialties in
      spite of the fact that an estimated 9.6 million francs could have been saved if
      these equivalent, alternative drugs had been prescribed. The potential saving
      corresponds to 6.5 per cent of the total observed cost. The care given to
      severely hypertensive patients is sub-optimum when compared with the ANAES
      guidelines (1997). In public health terms, the most preoccupying feature is poor
      blood pressure control because it occurs in a patient population with a high
      cardiovascular risk. These findings fully justify the continuation and
      amplification of the actions undertaken in this nationwide public health
      programme concerning the medical care given to hypertensive patients.

PMID- 11471362
TI  - [Prevention in cardiovascular pathology].
AB  - National and international recommendations on the management of arterial
      hypertension and hypercholesterolemia suggest a treatment decision based on the
      evaluation of absolute cardiovascular risk. In order to evaluate the
      cardiovascular risk level, Anderson's equation (Framingham) has been proposed but
      does not apply to the French population. In medical practice, cardiovascular risk
      has to be appreciated according to the estimated cardiovascular risk of the
      country or area. The limits of a decision based on cardiovascular risk have been
      emphasized, particularly the balance age/life expectancy in respect of early
      prevention of atherosclerosis. However, the benefit of treatment of hypertension
      with beta-blockers, diuretics and recently ACE inhibitors and calcium antagonists
      or hypercholesterolemia with statins has been clearly stated--the higher the
      cardiovascular risk the higher the benefit. Secondary prevention in patients with
      major cardiovascular events is effective and necessary. The discussion concerns
      only primary prevention and from an economic point of view may concern patients
      at high cardiovascular risk. The general population have to be informed on
      cardiovascular risk factors, and patient education must be encouraged and
      developed via the healthcare network.

PMID- 11471363
TI  - [Cost effectiveness of GM-CSF in the treatment of acute myeloblastic leukemia in
      aged patients: protocol of GOELAM Sa3].
AB  - A cost-effectiveness analysis was carried out from a randomized placebo
      controlled protocol of GM-CSF during and after remission induction treatment for
      elderly patients with acute myeloid leukemia (AML). A retrospective economic
      analysis was carried out from the hospital perspective. A total of 240 patients
      with de novo AML and aged 55 to 75 years were enrolled. Overall survival and
      disease-free survival were analysed for efficacy within five years and expressed
      in gained life-years. Analysis was also conducted according to the protocol
      stratification: 55-64-year-old and 65-75-year-old patients. Global costs were
      estimated on the basis of patient medical records from inclusion to death or
      relapse. In all, 83 patients were evaluated from three centres, Besancon, Nancy
      and Nantes. Costs are expressed in French francs. Overall, total cost per patient
      amounted to FF 641,778 for placebo patients and to FF 587,048 for GM-CSF
      patients. For disease free-survival, costs were FF 357,167 for placebo patients
      and FF 320,736 for GM-CSF patients. For overall survival and disease free
      survival the cost savings by GM-CSF were, respectively, FF 54,730 and FF 36,431.
      In the younger patient group savings were synonymous with GM-CSF. In all cases GM
      CSF strategy induced benefit expressed as savings as well as efficacy.

PMID- 11471364
TI  - [Interest in and limitations of economic assessment applied to the evaluation of
      medical strategies: examples in oncological hematology].
AB  - Using examples of economic assessment of medical innovations in the field of
      oncology, haematology and safety of blood products, the article shows that most
      of these innovations follow a law of diminishing returns: increasing levels of
      resources must be devoted in order to obtain an additional unit of health benefit
      (such as a life-year saved by a medical intervention). The article argues that,
      in such a context, cost-benefit analysis, a standard method in public economics,
      can be a useful tool to determine the 'optimal' level of resources that should be
      allocated by society for various medical interventions. In some instances, cost
      benefit analysis can help to identify barriers to optimal diffusion of medical
      innovations that are due to inappropriate incentives and constraints in the
      management of the healthcare system.

PMID- 11471365
TI  - [Impact of Opposable Medical References (RMO) prescription guidelines for
      antibiotic prescriptions in ambulatory medicine].
AB  - The French RMO (References Medicales Opposables) are prescription guidelines
      based on a critical assessment of antibiotic drug prescription. The RMO 2, which
      concerns the prescription of commonly used antibiotics for
      otorhinolaryngological/respiratory infections, provides an example of the
      advantages and drawbacks of such an approach. Its effect on prescription
      behaviour is probably significant. The economic impact in terms of health cost
      has remained within acceptable limits.

PMID- 11471366
TI  - [Home respiratory care].
AB  - In 1980, 11,000 French patients were given home respiratory care (HRC); today
      there are ten times more cases, i.e. about 120,000. There are two principal
      conditions in this population: chronic severe lung disease (CSLD), treated mainly
      with long-term oxygen therapy and assisted ventilation, and sleep apnoea syndrome
      (SAS), treated with continuous positive airway pressure (CPAP), a treatment that
      first became available in 1985. The mean age of patients with CSLD is currently
      67 years and is increasing annually, while for SAS it is 58 years. The
      constraints of treatment, prescribed for the rest of the patient's life, are
      incompatible with long-term hospitalization, given the daily length of treatment
      (12-24 h for CSLD, and 5-8 h at night for SAS). The number of medical and social
      workers involved in providing these types of treatment requires complex
      coordination for the patient to be able to benefit from such highly cost
      effective medical and technical services. In the case of home respiratory care,
      France has benefited for almost twenty years from the services of a not-for
      profit network that comprises a national coordinating body, ANTADIR, and regional
      HRC services administered by physicians specializing in pneumology or
      resuscitation, often from university hospitals.

PMID- 11471367
TI  - [Short emergency hospitalization].
AB  - In France, the number of admissions to emergency departments increase by 5 to 10
      per cent per year. Traditionally, patients who require services beyond the first
      hours in the emergency department have been admitted to the acute care hospital.
      Observation unit are becoming common in hospitals because they allow an
      additional option to admission or discharge. In France, 60 per cent of emergency
      departments have observation units. Five to ten per cent of patients seen in an
      emergency department are transferred to the observation unit. These observation
      units are staffed with emergency personnel specifically assigned to the function
      of the unit. The average period of observation is less than 48 h. Of the patients
      observed, 50 per cent are discharged after extended observation and treatment.
      These observation units can be a safe, effective and cost-saving way of ensuring
      that patients who are considered to be in an intermediate category receive
      appropriate care.

PMID- 11471368
TI  - [Medical ethics on risks of health care].

PMID- 11471369
TI  - [Prevention of avoidable iatrogenic disease: when patient safety joins with
      health care economics].
AB  - The prevention of preventable adverse therapeutic events (iatrogenic), especially
      drug related, is a major medical goal for patients, economics and the community.
      Its incidence is 5 to 15 per cent of hospitalization days. Preventable iatrogenic
      is a main problem in terms of public health owing to its human and economic
      consequences. Prevention of iatrogenic is based on better knowledge of its
      reality, on well-adapted initial and long-term intensive training of physicians,
      other healthcare workers and also patients and citizens. A better healthcare
      system is also needed.

PMID- 11471370
TI  - [Modalities of discovery and biological diagnosis of dyslipidemias in primary
      prevention. A.N.A.E.S.--National Agency of Health Accreditation and Evaluation].

PMID- 11471371
TI  - [Care of bronchiolitis in infants. September 21 2000, Salle Louis Armand, Cite
      des Sciences et de l'Industrie del la Villette, Paris. A.N.A.E.S. National Agency
      of Accreditation and Evaluation of Health and URML--Regional Union of Independent
      Physicians of the Ile de France].

PMID- 11471372
TI  - [Fatal toxic epidermal necrolysis associated with tetrazepam.

PMID- 11471373
TI  - [Fatal poisoning by cibenzoline].

PMID- 11471374
TI  - [Case report of fatal hepatitis from diacerein].

PMID- 11471375
TI  - [Pharmacologic dependence on nefopam (Acupan): a case report].

PMID- 11471376
TI  - Effect of some Moroccan medicinal plants on mosquito larvae.

PMID- 11471377
TI  - [Third Colloquy of the APNET senate (November 17 2000): speech of Senator Lucien
      Newwirth].

PMID- 11471378
TI  - [Therapeutic progress, innovations and health economics. Introduction the the
      Third APNET Conference].

PMID- 11471379
TI  - [Introduction to pharmaco-economics: 'glossary'].

PMID- 11471380
TI  - [Quality is expensive].
AB  - Over the past decade, as pressure to control costs has accelerated, the term cost
      effective has come increasingly into common usage. The central purpose of cost
      effectiveness analysis is to compare the relative value of different
      interventions in creating better health. This article presents the rationale for
      using such an approach to prioritize public and private healthcare programmes.

PMID- 11471381
TI  - [Quality in health care. What quality? Judged by which criteria? By whom? How?].
AB  - Quality in healthcare has to evaluate the efficacy, the cost effectiveness and
      patient satisfaction. Quality of treatment could be evaluated with randomized
      clinical trials and with satisfaction measurement, leading to professional
      recommendations. Quality of therapeutic strategy is based on the evaluation of
      patient monitoring. The quality of the healthcare worker is based on initial
      training, accreditation and various audits. The final quality in healthcare
      depends on the competence of the prescriber but also on the medical information,
      the logistics and the control of prescriptions. Improvements in quality will be
      obtained by better medical training, patient information and application of
      professional recommendations. These recommendations have to change gradually to
      be adapted to medical progress and evidence-based medicine.

PMID- 11471382
TI  - [Role of microcirculation in multiorgan failure of infectious origin].
AB  - The normal host response to infection is a complex process which serves to
      localize and control bacterial invasion and to initiate repair of injured tissue.
      This inflammatory process is accompanied by activation of circulating and fixed
      phagocytic cells and generation of pro-inflammatory and anti-inflammatory
      mediators. Sepsis results when the prerequisite inflammatory response to
      infection becomes generalized, and thereby extends to involve otherwise normal
      tissue which is remote from the initial site of injury or infection. Sepsis is
      typically associated to cardiovascular alterations that have been characterized
      by increases in oxygen delivery to the tissues. Paradoxically, the host's
      systemic inflammatory response syndrome may simultaneously disturb the ability to
      adequately match tissue oxygen needs and availability at a time when tissue
      oxygen needs are typically increased. Depressed tissue oxygen availability
      relative to augmented needs may result from dysfunction at all of the central,
      regional, and microregional levels of the circulation. Significant dysregulation
      in the process by which oxygen availability is usually matched to changing tissue
      oxygen needs is typical associated with changes the microvascular blood flow
      behavior, vascular reactivity and endothelial and leukocyte activation. Specific
      tools developed to explore the microcirculation have been applied in the setting
      of both human and animal models sepsis. Abnormalities observed in the septic
      microvasculature are characterized by reductions in cutaneous and skeletal muscle
      blood flow and in mucosal intestinal ischemia and hypoxia. Regarding the skeletal
      muscle organ system, microvascular abnormalities were further characterized by an
      impairment of blood flow to increase in response to oxygen need increase. Also,
      microvascular abnormalities in the intestine were associated with evidence of
      endothelial and leukocyte activation leading to epithelial dysfunction. Thus,
      sepsis appears to be associated with early onset microvascular dysfunction. The
      relationship between microvascular dysfunction and endothelial and leukocyte
      activation leading to organ failure has been suggested by numerous studies.

PMID- 11471383
TI  - [Volume expansion during septic shock].
AB  - At its very early phase, septic shock is characterized by severe hypovolemia
      related to abundant fluid losses, increased venous compliance and maldistribution
      of extracellular fluid (interstitial edema, splanchnic pooling). It results in a
      drop in venous return and cardiac output. Volume expansion, with crystalloids or
      colloids produces a hyperdynamic state with high cardiac output and low
      peripheral resistances. The quantity of liquid administered rather than its
      composition is the main determinant. Clinical examination and hemodynamic
      monitoring (Swan-Ganz catheter) appear to provide the most useful criteria to
      assess the limits of liquid administration. Better understanding in the
      mechanisms of circulatory dysfunction due to the inflammation cascades might soon
      lead to a new approach in fluid therapy.

PMID- 11471384
TI  - [Corticotherapy in severe infectious states].
AB  - Septic shock is one of the leading cause of death in modern countries. Scientists
      have made huge improvement in the understanding of mechanisms of inflammation,
      and the sequence of activation of the various pro and anti-inflammatory markers
      is now well known. By contrary, physicians have failed to improve survival from
      septic shock, in spite of the development of specific targets of the various
      points of the cytokine cascade sought to have a key role in host survival to
      sepsis. Corticosteroids were among the first anti-inflammatory drugs, which have
      been tested in high quality randomised controlled trials. These trials clearly
      showed that patients with septic shock are unlikely to benefit from a short
      course of a large dose of an anti-inflammatory steroid. More recent findings
      highlighting the role of the integrity of the hypothalamic-pituitary -adrenal
      axis to appropriately respond to a septic insult, have led to a reappraisal of
      the use of steroids in septic shock. Several high quality randomised controlled
      trials have evaluated the efficacy and safety of a prolonged treatment with low
      dose hydrocortisone in severe sepsis. These trials strongly suggested that this
      strategy of corticotherapy reduced the morbidity of septic shock and may
      favourably affect survival from septic shock.

PMID- 11471385
TI  - [New techniques in artificial ventilation].
AB  - In recent years, considerable improvement has been achieved in the field of
      mechanical ventilation. A lot of experimental and clinical research has been done
      to reduce the adverse effects of mechanical ventilation. It is currently of
      importance that high volumes and pressures have been demonstrated as sources of
      alveolar-capillary membrane injury in lungs. In the acute respiratory distress
      syndrome, mechanical ventilator settings have evolved from the goal of strict
      correction of gas exchange towards a lung-protective strategy where priority is
      given to tidal volumes limitation and alveolar recruitment. Pressure-assisted
      ventilatory modes, such as pressure support have been introduced, resulting in
      better patient-ventilator synchronisation, good tolerance and easier weaning
      process. Pressure support is also a largely used mode in noninvasive ventilation
      which has been proved to improve outcome in chronic obstructive pulmonary
      diseases.

PMID- 11471386
TI  - [The performance of intensive care services].
AB  - To evaluate the performance of intensive care unit (ICU) the severity scores are
      measured on the first day; organ system dysfunctions are measured several times
      during the stay. The severity scores are developed from large data bases of
      thousands of patients. They include the patient age, previous health status,
      severity and sometimes the main diagnosis. Prediction models are published to
      evaluate the risk of death for each patient. By adding the risk of death of each
      patient and dividing by the number of patients, the expected mortality rate is
      calculated. By comparing the observed and expected mortality rates the Standard
      Mortality Ratio (SMR) may be measured. The data collection must be rigorous, the
      studied population must be similar to the population of the large data bases.
      Other elements of performance may be evaluated, such as the cost-efficiency or
      the quality of life or surviving patients.

PMID- 11471387
TI  - [Vascularized peroneal reconstruction after bloc resection of tumors or
      congenital malformations of the upper limb in children].
AB  - Limb salvage surgery is the standard care for most malignant tumor affecting the
      extremities in the child, and a vascularized fibula transfer is probably the most
      popular microsurgical option to reconstruct long-bone defects. Between 1994 and
      1999, nine children with intractable diseases of the upper limb were treated
      using free vascularized fibula grafts (one patient had resection in 1983 and
      initially prosthetic reconstruction, then fibula transplant in 1996). There were
      6 boys and 3 girls. Mean age was 10 years (between 6 and 16). Eight patients had
      defects after sarcoma resection, one had an aggressive enchondroma. The
      reconstructed sites were the humerus (= 6), the radius (n = 3). The length of the
      bone defect ranged from 8 to 19 cm (mean: 14.4 cm). The fibula head with the
      cartilage and the growth plate was used in 3 children. One girl, 4.5 years old
      with congenital pseudoarthrosis of radius and cubitus had a resection and
      reconstruction with a U shaped fibula transplant. One patient died from lung and
      brain metastasis, two years after the reconstruction. There were no local
      recurrences. The complications were numerous but usually benign; fracture of the
      grafted fibula n = 7, necessity of additional bone grafts (n = 4) malunion (n =
      1) needed reoperation, pseudoarthrosis (n = 2) with reoperation, ankle valgus (n
      = 1) required reoperation, necrosis of the fibula head (n = 1), radial
      inclination (n = 1). The ten patients had bone union. The mean period required to
      obtain radiographic bone union was 5 months. The functional results of the
      remaining patients were evaluated according to the scale of ENNEKING. The results
      ranged from 21 to 30 points. Our results were satisfactory with regard to pain,
      emotional acceptance, manual dexterity. The vascularized fibula graft is
      indicated in children with large bone defects, more than 8 cm in the humerus,
      radius and ulna.

PMID- 11471388
TI  - [Does diffusion and perfusion MRI modify the diagnosis and management of cerebral
      ischemic accidents?].
AB  - Since 25 years, CT has the capability to recognize hemorrhagic infarcts in
      emergency. On the other hand, cytotoxic oedema is visible only 12 or 24 hours
      after the onset of the ischemic stroke. T2 weighted MR-sequences are more
      sensitive and few hours after the onset, cytotoxic oedema appears as hypersignal,
      particularly using FLAIR sequences (Fluid Attenuated Inversion Recuperation).
      Described in 1986, diffusion-weighted MRI is a very sensitive technique to detect
      the cytotoxic oedema few minutes after the onset. The attenuation of the apparent
      diffusion coefficient must be evaluated with a map. This attenuation appears as
      hypersignal and its sensibility is close than 100%. The mismatch between data of
      perfusion MRI and diffusion MRI is the area of the ischemic penumbra. These new
      MRI techniques are easy to learn and must be available 24 h a day and 7 days a
      week in the stroke centers. They are simple, rapid and highly accurate for the
      diagnosis of acute ischemic stroke. They could be useful to select candidates to
      aggressive therapy during the first 3 or 6 hours. Potentially, they improve
      patient's outcome.

PMID- 11471389
TI  - [Neoadjuvant treatment in surgery of esophageal cancer].
AB  - We conducted a prospective study on neoadjuvant treatment for squamous cell
      carcinoma of the esophagus, modifying the chemotherapy protocol by adding l
      folinic acid and giving bifractionated radiotherapy with a cis
      diaminedichloroplatinum (CDDP) injection before each fraction. Thirty-two
      patients, 30 men, 2 women, mean age 56.2-8.9 years, with resectable squamous celi
      carcinoma of the esophagus (TNM stage I = 4, IIA = 4, IIB = 13, III = 11) were
      included. Chemotherapy, CDDP (80 mg/m2: D2), 5-fluorouracil (5-FU; 600 mg/m2, D1
      4), and 1-folinic acid (200 mg/m2, DI-4), was given in two sessions with a 3-week
      interval during which the patients received radiotherapy (45 Gy), two fractions
      per day (150 cGy/fraction). A 3-mg Injection of CDDP was given prior to each
      fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. No
      severe side effects were observed in 12 patients. Grade 3 effects (WBC,
      platelests, mucosite's) occurred in 16 patients and grade 4 effects (platelets,
      mucositis) in four including 1 death due to septicemia with an infected catheter.
      Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative
      mortality was 10%. The 26 surgical specimens showed complete response (n = 18),
      persistent microscopic residues (n = 4), or not significant modification (n = 4).
      Survival at 1, 3, and 5 years was 82, 47, and 47% and disease-free survival was
      77, 47, and 47% respectively. This new therapeutic combination is aggressive and
      associated with a high postoperative mortality but has a remarkable histological
      effect since complete response was achieved in 56% (95% CI: 39-73%) of the
      patients and 5-year survival reached 47%, a very high rate in our experience.

PMID- 11471390
TI  - [Inhaled nitric oxide: therapeutic applications in cardiac surgery].
AB  - The occurrence of right ventricular failure secondary to pulmonary arterial
      hypertension is a major postoperative complication of cardiac surgery in children
      and adults. The selective pulmonary vasodilation produced by inhaled nitric oxide
      (NO) constitutes a fundamental therapeutic advance in the management of this
      pathology. NO binds immediately with haemoglobin, resulting in its immediate
      inactivation. This results in perfect maintenance of systemic and coronary blood
      pressures. A first study performed in 1989 after mitral valve replacement for
      mitral stenosis with pulmonary hypertension and clinical trials after surgical
      correction for congenital heart disease and heart transplantation with pulmonary
      hypertension suggested the efficacy and safety of 20 to 40 ppm NO concentrations
      in these indications. Potential toxicity of NO (NO2 production by oxidation,
      methaemoglobin formation) leads to caution with its use. Monitoring of NO
      concentration and methaemoglobin production is recommended, especially in new
      borns.

PMID- 11471392
TI  - Developmental coordination disorder.

PMID- 11471391
TI  - [Local curative treatment of superficial adenocarcinoma in Barrett's esophagus.
      First results of photodynamic therapy with a new photosensitizer].
AB  - Pre-cancerous lesions and mucosally confined superficial cancers can benefit from
      local therapy given with curative intent due to the absence of near metastatic
      lymph nodes. Photodynamic therapy (PDT) which acts by laser irradiation with an
      appropriate wave-length after administration of  a photosensitiser retained
      preferentially by the cancerous tissue can destroy tumour cells selectively, but
      its efficiency depends upon the photosensitiser. The results presented concern 10
      sites on Barrett's mucosa (BO). They consisted of  either an association of
      intramucosal cancer (IMC) with high-grade dysplasia (HGD) or of high-grade
      dysplasia alone. The method consisted of intravenous injection of Temoporfin 0,15
      mg/kg 4 days before irradiation of  the lesion with a green laser light emitting
      514 nm through a windowed diffuser. The light fluence was 75 J per cm2 and
      irradiation 100 mW per cm2. Irradiation time was 12,5 mn. Omeprazole was
      routinely prescribed after treatment at a dose of 40 mg daily. The follow-up
      protocol was 2 years with endoscopic surveillance at 2, 3, 6, 12, 18 and 24
      months. Biopsies obligatory at 2 and 3 months were in fact carried out at all the
      other delays. Efficacy was judged on the absence of high-grade dysplasia or intra
      mucosal carcinoma on biopsies at treated sites. Undesirable side effects noted
      have been moderate for the most part. No stenosis appeared. Treatment has been
      100% successful for the 10 lesion after 15 treatments with PDT. The follow up
      varies from 6-36 months and was more than 18 months for 6 lesions on 5 patients.
      Our series has demonstrated a great heterogeneity in lesions which were sometimes
      visible and highly localised, but more often invisible, multi-focal and
      diagnosable only by biopsy at different levels. In keeping with the literature
      and our experience, PDT   has several advantages over the other locally curative
      therapies, mucosectomy and thermocoagulation. These are the possible treatments
      without general anaesthesia, selectively for cancer cells, an action on more
      extensive areas with eradication of non visible lesions. Temoporfin has
      contributed notably to the field of photodynamic therapy compared to previously
      used sensitisers. It is a pure, synthetic product which guarantees more
      reproducible results. Compared with Photofrin, Temoporfin has many advantages
      with smaller doses of drugs and less energy, better selectivity and rapid
      elimination which reduce the risk period for photosensitisation. The frequency of
      important undesirable side effects is diminished. Finally, it produces a
      consistent effect on the surface and in depth producing a complete
      reepithelialisation of the treated zones. Subject to validation of the method on
      a greater number of  patients, the first results obtained on superficial cancer
      in Barrett's aesophagus allow us to propose green light Temoporfin PDT as an
      alternative first line therapy with curative intent.

PMID- 11471393
TI  - Perceptual skills of children with developmental coordination disorder.
AB  - The aim of this study was to investigate whether children with a Developmental
      Coordination Disorder (DCD) experience problems in the processing of visual,
      proprioceptive or tactile information. Different aspects of visual perception
      were tested with the Developmental Test of Visual Perception (DTVP-2), tactile
      perception was assessed with the Tactual Performance Test (TPT), and a manual
      pointing task was employed to measure the ability to use visual and
      proprioceptive information in goal-directed movements. Nineteen children with DCD
      and nineteen age and sex-matched controls participated in this study. Differences
      between groups were most pronounced in the subtests measuring visual-motor
      integration of the DTVP-2, and in two subtests measuring visual perception
      (visual closure and position in space). On average the children with DCD
      performed slightly below the norm for tactile perception, with only three
      children failing the norm. On the manual pointing task, children with DCD made
      inconsistent responses towards the targets in all three conditions (visual,
      visual-proprioceptive and proprioceptive condition). No significant differences
      between groups were found for absolute error. Inspection of the individual data
      revealed that only two children failed on the majority of perceptual tasks in the
      three modalities. Across tasks, no consistent pattern of deficits appeared,
      illustrating the heterogeneity of the problems of children with DCD.

PMID- 11471394
TI  - Abnormalities of motor and praxis imagery in children with DCD.
AB  - In an earlier study using the visually guided pointing task (VGPT) the authors
      showed that the timing of imagined movement sequences in children with
      developmental coordination disorder (DCD) does not conform to the conventional
      speed-for-accuracy trade-off (or Fitts' law [P.M. Fitts, Journal of Experimental
      Psychology 47 (1954) 381-391]) that occurs when the distance and accuracy
      requirements of movements are varied [P. Maruff, P.H. Wilson, M. Trebilcock, J.
      Currie, Neuropsychologia 37 (1999b) 1317-1324]. The present study sought to
      replicate this earlier finding and to examine (using a weight manipulation)
      whether this deficit was also attributable to inaccurate programming of relative
      force. The chronometry of real and imagined movements was investigated in a group
      of 20 children with DCD aged between 8 and 12 years and a group of controls
      matched on age and verbal IQ (VIQ). Movement duration was tested for real and
      imagined movements using the preferred hand, with the VGPT performed under two
      load conditions: with and without the addition of a weight attached to a pen.
      Group means of each subjects' mean movement duration were calculated and plotted
      against target width for each of the four conditions [Movement type (2) x Load
      (2)] and a logarithmic curve was fitted to the data points. In the control group,
      the speed-for-accuracy trade-off for both real and imagined performance conformed
      to Fitts' law under each load condition. In the DCD group only real movements
      conformed to Fitts' law. Moreover, the effect of load differed between groups-
      for real movements, movement duration did not differ between load and no-load
      conditions for either group, while for imagined movements, movement duration
      increased under the load condition for the control group only. These results
      replicate and extend the results of our earlier study. This pattern of
      performance suggests that children with DCD have an impairment in the ability to
      generate internal representations of volitional movements which may reflect an
      impaired ability to process efference copy signals. The ability to programme both
      relative force and timing appears to underly this difficulty. Results have
      implications for the use of (guided) motor imagery training in order to
      facilitate the development of motor skill in children with DCD.

PMID- 11471395
TI  - Fine motor deficiencies in children diagnosed as DCD based on poor grapho-motor
      ability.
AB  - A sample of 125 children from grades 4 and 5 of two normal Dutch primary schools
      were investigated regarding the incidence of handwriting problems and other fine
      motor disabilities. Handwriting quality was assessed with the concise assessment
      method for children's handwriting (BHK) and the school questionnaire for teachers
      (SQT). Two groups of 12 children each were formed, one group of good writers and
      a group of poor writers selected from the lower performance range. The latter
      group was investigated in depth by assessing general and fine motor ability using
      the Movement Assessment Battery for Children (M-ABC test) and the Motor
      Performance School Readiness Test (MSRT). We hypothesised that poor handwriting
      is part of a wider neuromotor condition characterised by faster and cruder
      movements, lack of inhibition of co-movements and poor co-ordination of fine
      motor skills. To test the theory kinematic measures of drawing movements were
      collected on the flower-trail-drawing item of the M-ABC test. Moreover, the
      experimental group of poor writers received physiotherapy during a three-month
      period and was tested for handwriting proficiency after therapy and again nine
      months later. The results revealed that 34% of the group of 125 children
      displayed handwriting problems. The analysis confirmed that serious handwriting
      problems are accompanied by fine motor deficits. We suggest that in these
      children an enhanced level of neuromotor noise is compensated for by enhanced
      phasic stiffness of the limb system. This results in higher movement velocity and
      fewer velocity peaks. In the children who received physiotherapy the quality of
      handwriting improved.

PMID- 11471396
TI  - A pilot trial of a cognitive treatment for children with developmental
      coordination disorder.
AB  - This pilot study compared a new treatment approach, the Cognitive Orientation to
      daily Occupational Performance (CO-OP) to the Contemporary Treatment Approach
      (CTA) to treating children with Developmental Coordination Disorder (DCD). CO-OP
      emphasises problem-solving strategies and guided discovery of child and task
      specific strategies. CTA encompasses a variety of approaches, such as
      neuromuscular, multi-sensory, and biomechanical, focusing on motor aspects of
      skill acquisition. Twenty children with a mean age of 9.05 years (S.D. = 1.23)
      participated in the study. All children had normal intelligence, scored below the
      15th percentile on a standardised test of motor ability, and demonstrated motor
      difficulties significant enough to warrant referral for treatment. Pre- and post
      measures included the Canadian Occupational Performance Measure (COPM), the
      Vineland Adaptive Behavior Scales (VABS), the Bruininks-Oseretsky Test of Motor
      Proficiency (BOTMP), the Developmental Test of Visual-Motor Integration-Revised
      (VMI), the motor items of the Self-Perception Profile for Children (SPPC), and
      the Performance Quality Rating Scale (PQRS). In both groups, treatment goals were
      child-chosen. Both treatments lead to improved COPM self-ratings of performance
      and satisfaction; however, improvements in the CO-OP group were greater than
      those in the CTA group. These results were paralleled by PQRS scores, and the
      Motor scores on the VABS, but not on the BOTMP measures. This outcome still needs
      replication as no control group was involved and because of the occurrence of pre
      treatment differences between the CO-OP and CTA groups on relevant measures.
      Follow-up data indicated that children who received CO-OP tended to experience
      greater long-term maintenance of their motor goals and acquired strategies;
      follow-up parent-report rated CO-OP treatment as more useful than CTA treatment.
      Self-report, observer report, standardised assessment, and follow-up all
      demonstrated the effectiveness of the CO-OP approach, supporting the use of CO-OP
      and suggesting further investigation of this new cognitive intervention.

PMID- 11471397
TI  - The search for subtypes of DCD: is cluster analysis the answer?
AB  - Studies using cluster analysis as a method to identify distinct subtypes of
      developmental coordination disorder (DCD) have been inconclusive leading some
      authors to conclude that the method of cluster analysis should be abandoned while
      others call for the validation of previously defined subtypes. The objective of
      the current study was to examine the use of cluster analysis as a method of
      searching for subtypes of DCD to gain a better understanding of how different
      samples and different measures influence the interpretation of results. The paper
      provides a detailed review of three commonly cited cluster analytical studies and
      then explores the possible reasons for the discrepant results by replicating the
      approach with a different clinical sample. The results highlight the impact of
      different measures on cluster structure and the importance of adoption of a
      common standard to facilitate interpretation across studies.

PMID- 11471398
TI  - Clinical and research diagnostic criteria for developmental coordination
      disorder: a review and discussion.
AB  - The aim of this review was to investigate the selection criteria used in the past
      in studies of children with developmental motor problems (excluding those
      suffering from neurological dysfunctions such as cerebral palsy, muscular
      dystrophy, etc.). We therefore conducted an extensive analysis of 176
      publications. First, an overview of the main characteristics of these studies
      (terminology, population, type and purpose) and the selection criteria that are
      reported in these publications are presented. Following this, the DSM-IV
      selection criteria for developmental coordination disorder (DCD) are contrasted
      with the selection criteria reported in 41 publications that have used this
      terminology to classify the children. The results of this comparison show that
      the inclusion criteria are largely followed, albeit with little consistency
      concerning selection instruments and quantitative cut-offs, while adherence to
      the exclusion criteria is not common practice. Strengths and weaknesses of the
      DSM-IV criteria, complementary to the previous discussion by Henderson and
      Barnett in the HMS special issue on DCD in 1998 on this same topic, are
      discussed. The results of the review also show that many studies have used
      additional selection criteria related to the specific research questions of the
      study concerned. In the broader context of clinical practice as well as basic
      research, the latter result suggests the usefulness of a distinction between
      Clinical Diagnostic Criteria and Research Diagnostic Criteria. This distinction
      helps to develop a unifying view on the use of diagnostic criteria for research
      and clinical practice. We conclude with a number of recommendations concerning
      the selection criteria for children with DCD.

PMID- 11471399
TI  - Psychosocial implications of poor motor coordination in children and adolescents.
AB  - Utilising Harter's theory of competence motivation (Harter, S. The determinants
      and mediational role of global self-worth in children. In: N. Eisenberg,
      Contemporary topics in developmental psychology, Wiley, New York, 1987, pp. 219
      242.), the current study examined perceived competence and social support, and
      their influence on self-worth and anxiety in children and adolescents with and
      without developmental coordination disorder (DCD). A group of children aged 8-10
      years, and a group of adolescents aged 12-14 years, with significant movement
      problems were compared with matched control groups on measures of perceived
      competence, perceived social support, self-worth and anxiety. Those with DCD were
      found to perceive themselves as less competent in several domains, and having
      less social support than control participants. Overall, DCD groups had lower self
      worth and higher levels of anxiety than the control groups. Adolescents also
      perceived themselves as less competent with poorer social support and lower self
      worth than younger children. In addition, anxiety was significantly higher for
      the adolescent group compared to their younger counterparts.

PMID- 11471400
TI  - A longitudinal study of motor ability and kinaesthetic acuity in young children
      at risk of developmental coordination disorder.
AB  - Several studies have linked poor kinaesthetic ability with poor motor
      coordination in school-aged children. However, few studies have investigated
      kinaesthesis in younger children. The aim of this study was to determine if
      preschool aged children who have been identified as at risk of developing
      developmental coordination disorder (DCD) have poorer kinaesthetic ability than
      matched controls. Kinaesthetic ability and performance IQ were examined in a
      group of children aged between 4 and 5 years. Following individual assessment of
      291 children, 31 were identified as at risk of DCD at this age. One year later,
      30 of these children were retested, and 23 were still found to be at risk. These
      children were matched on verbal IQ, age and sex with control children and their
      performance compared on the kinaesthetic acuity test (KAT) [D.J. Livesey and N.A.
      Parkes, Aust. J. Psychol., 47 (1995) 160] and three subtests of the WPPSI-R
      performance IQ (D. Wechsler, Manual for the Wechsler preschool and primary scale
      of intelligence--revised, Psychological Corporation, New York, 1989). Both the
      KAT and the performance subtest scores were found to be significantly poorer in
      the children at risk of DCD. Follow-up testing one year later showed that both
      groups improved their kinaesthetic acuity score although the control children
      remained significantly better than the children with poor motor coordination.

PMID- 11471401
TI  - [Hyperbaric oxygen therapy in trauma surgery].

PMID- 11471402
TI  - [Hyperbaric oxygen therapy in trauma surgery].
AB  - Hyperbaric oxygenation is achieved when a patient breathes 100 percent oxygen in
      an environment of elevated atmospheric pressure. Physiologically, this produces a
      directly proportional increase in the plasma volume fraction of transported
      oxygen which is readily available for cellular metabolism. A number of beneficial
      biochemical, cellular and physiologic effects result which account for the use of
      hyperbaric oxygen as an adjunctive therapy in the treatment of clostridial
      myonecrosis, crush injuries, compromised flaps, osteoradionecrosis and chronic
      problem wounds. Indications, modes of treatment, contraindications, side effects,
      costs and experimental and clinical results are presented. Overall, these data
      demonstrate that hyperbaric oxygen is no longer "a therapy in search of
      diseases". However, more randomized controlled clinical trials are necessary to
      demonstrate its efficacy.

PMID- 11471403
TI  - [Injury pattern in shoulder dislocation in the elderly patient].
AB  - PROBLEM: Recurrent shoulder dislocation is reported to be rare in older patients.
      While injuries of the glenoid labrum and the anterior capsule following primary
      dislocation in younger patients seem to determine the rate of instability, the
      pattern of damages in the elderly has rarely been studied. METHODS: 91 patients
      with an age older than 40 years with the diagnosis of primary (group A, n = 50)
      or recurrent (group B, n = 41) anterior shoulder dislocation were included in a
      prospective study. By analysis of the findings in x-rays, MRI, CT-scans and in 36
      patients of diagnostic arthroscopy the pattern of intra- and periarticular
      pathology was evaluated. RESULTS: While the incidence of bony Bankart- and Hill
      Sachs lesions was constantly spread over the age groups the pattern of soft
      tissue damages was different. Up to the age of 60 years lesions of the glenoid
      labrum were leading while in older patients the prevalence of rotator cuff tears
      became about 70 percent. CONCLUSIONS: The development of secondary osteoarthritis
      and persisting symptoms in older patients with rotator cuff tears after traumatic
      shoulder dislocation requires early diagnosis and appropriate treatment.

PMID- 11471404
TI  - [Intracompartmental pressure measurement in in acute compartment syndrome.
      Results of a survey of indications, measuring technique and critical pressure
      value].
AB  - The early diagnosis of acute compartment syndrome is very important, compartment
      monitoring is advocated. There is however still some controversy regarding the
      use of compartment pressure measurement devices in the diagnosis of acute
      compartment syndrome. We present the results of a survey that was designed to
      explore this issue in Germany. In the case of suspected acute compartment
      syndrome 50.9% (n = 214) of the surgeons perform intracompartmental pressure
      measurement. Pressure measurement is of lower significance for 61.8% (n = 215)
      surgeons questioned. Additional apparative diagnostics is performed by 41.7% of
      the surgeons. A large majority apply the Stryker device (63.1%, n = 135),
      followed by the Coach device (12.1%, n = 26). The pressure threshold for
      intervention is recommended by 51.4% (n = 110) of the traumatologists as an
      absolute compartment pressure value. The remaining 48.6% (n = 104) include
      haemodynamic parameters in their decision. The surgeons employ widely differing
      methods of approach in the diagnosis of acute compartment syndrome. Some of these
      are extremely different from the methods recommended in the literature.

PMID- 11471405
TI  - [Scapho-lunate ligament reconstruction with Mitek suture anchors. Initial
      clinical results].
AB  - The scapholunate dissociation is an often misjudged lesion of carpal ligaments as
      clinical and radiological signs often don't allow a clear interpretation. Apart
      from chronical courses with increasing arthrosis the consequences are limited and
      more difficult operations. The application of Mitek suture anchors is a new and
      simple supplement to large-scale operative reconstructions of ligaments or
      partial arthrodesis. Of nine reconstructions of the scapholunate interosseous
      ligament using this anchor method so far only one relaps occurred.

PMID- 11471406
TI  - [Diagnosis of intra-articular fracture of the head of the tibia. A prospective
      comparative study].
AB  - Complete visualization of the joint surface is essential for correct assessment
      of tibial head fractures. Conventional tomography, computed tomography (CT), and
      magnetic resonance imaging (MRI) are compared in this prospective study. We
      examined 27 patients (19 suffering from B fractures and 8 from C fractures) from
      1 January 1995 to 11 November 1998. Conventional tomography underestimated the
      fractures in 3 of the 19 cases of B fractures. Computed tomography underestimated
      two of these cases. MRI could not exactly depict the essential structures in
      three of the eight cases of C fractures because of edema and effusions. MRI
      identified complete cruciate ligament rupture in 6 of the 27 cases (18%) and 10
      meniscal ruptures in 9 cases (33%: 6 medial meniscus, 4 lateral meniscus).
      Complete ruptures of the lateral collateral ligament were detected in five cases
      and medial collateral ligament ruptures in two cases. According to this, 63% of
      the patients suffered from relevant accompanying soft tissue injuries. The rate
      of soft tissue injuries increased up to 92% including the partial collateral
      ligament ruptures. Local hospital conditions permitting, X-ray-loaded
      conventional tomography should no longer be used in tibial head fractures. X-ray
      free MRI is most efficient in cases of B fractures, which can in most cases be
      treated with a minimum of invasive techniques. Computed tomography is to be used
      in cases of C fractures that are regularly managed by open surgery accompanied by
      direct visualization of the inside of the knee joint.

PMID- 11471407
TI  - [Intraoperative Doppler ultrasound of the femoral vein for maintaining venous
      patency in hip joint prosthesis implantation].
AB  - PROBLEM: Is the femoral vein occluded during insertion of the stem? Can
      thrombembolic complications be reduced by avoiding occlusion? METHODS: In a
      prospective randomized study 160 cemented stems were implanted from the
      anterolateral approach: 76 patients had conventional figure-of-four positioning
      of the femur, 84 patients had a modified position according to the blood flow
      registered by intraoperative Doppler sonography. RESULTS: 68.7% of the 84 femoral
      veins were completely occluded in the figure-of-four positioning. Only by
      reduction of this position and soft tissue release, venous flow could be
      demonstrated by sonography. Increased body mass index (BMI) and age correlated
      with occlusion (p = 0.0001 and p < 0.05). In the 84 patients no thrombembolic
      complication was found. In the control group 3 deep thromboses were revealed by
      venography (p = 0.105). CONCLUSION: Doppler sonography helps guaranteeing venous
      drainage. A modified leg position should be aimed at especially in increased BMI
      and age.

PMID- 11471408
TI  - [A holder for standardized radiological detection of ulnar capsule-ligament
      lesions of the thumb base joint].
AB  - AIM OF THE STUDY: To evaluate the usefulness of a self-constructed holding device
      for standardized, investigator-independent radiodiagnostics for ulnar capsulo
      ligamentous lesions of the thumb metacarpophalangeal joint compared to the
      uninjured side. MATERIAL AND METHODS: A holding device for stress roentgenograms
      was constructed. Normal abduction arcs were evaluated in 20 degrees flexion in 28
      healthy volunteers. The investigator-dependent variance was assessed. The study
      group comprised 123 consecutive patients (68 male, 55 female, aged 7 to 68 years,
      mean age 30 years). RESULTS: The normal arc of abduction was calculated to be 12
      degrees (range 3 degrees to 24 degrees), while the mean individual difference in
      side by side comparison in volunteers was 0.3 degree (SD 2.69 degrees, range 0
      degree-8 degrees). A rupture was diagnosed in 47 patients; 41 were operated. The
      preoperative diagnoses confirmed correct in all operated patients. A difference
      of greater than 6 degrees is indicative of a rupture with a sensitivity of 66.7%
      and a specificity of 96.9%. CONCLUSIONS: In summary, the holding device is useful
      for the practical work. Individual differences of less than 4 degrees are
      negative, between 4 degrees and 7 degrees questionable positive, between 7
      degrees and 12 degrees are positive and over 12 degrees proof indicator of a
      rupture of the ulnar collateral ligament of the thumb metacarpophalangeal joint.

PMID- 11471409
TI  - [Clinico-functional results of constrained knee endoprostheses].
AB  - AIM OF THE STUDY: To assess the clinical and functional outcome after
      implantation of a constrained knee arthroplasty. MATERIAL AND METHODS: 14
      patients with a revision of the primary prostheses with constrained knee
      arthroplasties ("Genesis constrained" and "Blauth") were evaluated in the
      operated and non operated leg at an average follow-up of 8.5 months (range 6.5 to
      61.4 months). The study included clinical examinations as well as gait analysis
      and surface electromyography. The results were compared with a group of healthy
      volunteers. The clinical examinations were scored with the HSS, the Knee Society
      Score, the Tegner Activity Score, the Patella Score and the Visual Analogue
      Scale. Gait analysis was performed with a three dimensional motion analysis
      system. Surface electromyography was evaluated bilaterally from the rectus
      femoris, vastus medialis and lateralis, semitendinosus, biceps femoris (long
      head), tibialis anterior and gastrocnemius (medial head). RESULTS: The comparison
      between the healthy volunteers and the patients showed significant functional
      deficits in the patient group. The electromyography demonstrated significantly
      lower peak amplitudes in 5 of 7 muscles. In all parameters--except for knee
      extension--gait analysis resulted in significant differences between the patient
      and control group. The comparison between the operated and non operated leg
      showed a significant difference only for knee extension. The patients revealed a
      bilateral functional deficit so that gait symmetry was preserved. CONCLUSION: The
      presented results indicate that the functional deficits may be caused by
      preoperative deficits and are not only due to the operation. It can be supposed
      that the gastrocnemius is more important because of the high correlation with the
      clinical results. The value of pre- and postoperative rehabilitation programs to
      prevent postoperative functional deficits can be concluded.

PMID- 11471410
TI  - [Arthroscopic and clinical evaluation after isolated, augmented anterior cruciate
      ligament replacement. A prospective study].
AB  - 80 patients were examined in to perform a prospective essay on the isolated
      substitute of the anterior crucial ligament being done by Miniarthrotomie and two
      channel technique. All patients received a substitute of the anterior cruciate
      ligament by using an autogenous, TETRA-L3 augmentated bone tendon bone graft from
      the middle third of the patellar ligament of the injured knee. Clinical and
      arthroscopical examination was carried out in the average 28 months (24-36) after
      crucial ligament reconstruction, by the routinely removal of the augmentation and
      fixation material. Clinical examination was carried out using the strict and
      objective IKDC-Score. The arthroscopical evaluation of the ACL-graft was
      performed with our recently developed Score for ACL-graft evaluation (Marburger
      Arthroscopy Score for graft evaluation). The Score distinguishes between four
      stages: type I: tight, crucial ligament like structured graft, type II: a firm,
      more bundle like structured graft, type III: a lax, untidy structured graft and
      type IV: the rudimentary graft. A statistical analysis was performed on the
      question whether there is a correlation between the clinical and the
      arthroscopical results. Furthermore, with the Marbuger Arthroscopy Score for
      graft Evaluation we introduced a standardised, simple-to-use new score for the
      arthroscopical ACL-graft evaluation. We find a high correlation (r = 0.77)
      between the clinical results and the arthroscopical findings, so that from
      clinical evaluation there might be draw conclusion to the arthroscopical
      expective results with high probability. Due to our previous experience we assume
      the Marburger Arthroscopy Score For Graft Evaluation to be a standardised and
      simple assessment method for the evaluation of the ACL-graft, considering
      pathobiomechanical influences on the ACL-substitute.

PMID- 11471411
TI  - [Rehabilitation of trauma surgery patients. Presentation of 3 treatment
      elements].

PMID- 11471412
TI  - [Nocturnal spinal fracture--first manifestation of epilepsy].
AB  - A 54-year-old patient suffered overnight a double thoracic burst-fracture. One
      week later during the investigation for a metabolic or endocrinological cause, a
      witnessed seizure led to an unstable fracture of the humerus and the scapula. The
      neurological work-up revealed a cerebral astrocytoma as the epileptogenic focus.
      Forces generated during a tonic-clonic seizure can result in axial skeletal
      trauma, including thoracic and lumbar burst fractures. Vertebral fractures
      unrelated to an exogenous trauma are therefore always suspicious of an underlying
      epileptic disease.

PMID- 11471413
TI  - [Fatal pelvic vein injury caused by guidewire used with the dynamic hip screw].
AB  - There are only a few reports about injury to vital anatomical structures by
      Kirschner wires in literature. In the case described here the guide wire of the
      dynamic hip screw caused a fatal injury to the external iliac vein which was not
      at first evident. The guide wire had obviously become caught up in the
      combination three-diameter drill and screwed by the drill into the pelvis. After
      a stable interval the patient suffered circulatory collapse. Emergency treatment
      and resuscitation attempts followed with no possibility of surgical intervention.
      The nature of the injury was established and described in a postmortem
      examination (photos). The distances were measured on the actual bone. The
      conclusion of the two experts assessing this case was that this rare injury was
      not due to malpractice.

PMID- 11471414
TI  - [Isolated rupture of the biceps tendon of the knee joint].
AB  - Traumatic injuries of the posterolateral structures of the knee are normally the
      result of a severe rotation trauma, and as a rule, associated with intraarticular
      lesions. Two cases will be presented, whereby, without injuries to the knee, an
      isolated rupture of the distal part of the biceps femoris tendon occurred.
      Intraoperatively as also histologically there was no evidence of degenerative
      changes. The operative treatment in both cases achieved a good functional result.
      The better result was achieved with rigid fixation and a limiting protective
      rehabilitation program as it is used after the operative reconstruction of the
      torn posterolateral structures.

PMID- 11471415
TI  - [Perthes syndrome. The classical symptom triad as a rarity in trauma surgery
      practice].
AB  - Perthes syndrome or traumatic asphyxia is a condition characterised by
      subconjunctival hemorrhage, cervicofacial petechiae and cyanosis caused by severe
      compression of the chest. Diagnosis is made by history and clinical examination.
      Associated injuries such as intrathoracic or abdominal lesions can be life
      threatening and must be strictly assessed. This report demonstrates an
      illustrative case of this rare injury.

PMID- 11471416
TI  - Are rural doctors held to big-city standards?

PMID- 11471417
TI  - What it will take to fix the system. Roundtable discussion.

PMID- 11471418
TI  - You'd better be able to answer these legal questions.

PMID- 11471419
TI  - How good are the specialists you refer to?

PMID- 11471420
TI  - 12 surefire ways to lose patients.

PMID- 11471421
TI  - [Effectiveness of a systematic treatment model in an inpatient department of
      child and adolescent psychiatry].
AB  - This is a report on the findings of the effectiveness of the "Viersener Modell",
      a inpatient systemic child psychiatry model. The therapy effects were recorded,
      by means of self and therapists assessment, in several relevant areas of change.
      The index clients (ic) show typical characteristics of a child psychiatry
      population. The ic (n = 43) and also their parents (37 mothers and 22 fathers)
      showed significant improvement on the level of psychiatric symptoms, individual
      problems and in general experience and behavior. The psychiatric symptoms that
      were conspicuous by both ic and parents at the beginning of therapy, were mainly
      inconspicuous at the end of the treatment (effectsize (es): icfemale, n = 28 =
      .82, icmale, n = 15 = .22, motherswithout partner(accompanying) = .20,
      motherswith partner(accompanying) = .44, fathers = .44). There was no essential
      improvement in the quality of the couples relationship, on the other hand the
      relationships were not clinically conspicuous at the beginning of therapy. Family
      members and therapists assessed quality of the treatment results and process
      mainly in accordance with our hypothesis. While the therapists noticed a
      significant improvement in the functioning of the family relationships (es = .87)
      at the end of the therapy, the parents (reported no difficulties in family
      functioning at the beginning of therapy) reported no essential improvement of
      family relationships in the follow-up questionnaire (n = 32). The improvement of
      the problems and the assessment of the quality of the treatment results remained
      stable over an eight month period.

PMID- 11471422
TI  - [Psychosocial determination of depressive symptoms in adolescence: sex
      differences].
AB  - In a longitudinal study over four years, the links between psychosocial factors
      of the social network and depressive symptomatology were analysed in 107
      adolescents. Separate regression analysis for each gender revealed different
      factors contributing to female and male depression in late adolescence. While
      females' psychological well-being seems to depend on psychosocial characteristics
      of their social world, which may serve as protective factors, male depression is
      primarily determined by former depression, whereas social factors serve as
      stressors.

PMID- 11471423
TI  - [Evaluation of integrative group therapy with children].
AB  - The purpose of this study consists in the investigation of the effectiveness of
      an Integrative Group Therapy involving children from a social focus area. The
      research has been made on a group therapy covering a total of 22 therapeutic
      sessions with six "marginalised children" aged seven to nine attending the second
      class of a primary school. The children suffered from considerable concentration
      and attention problems affecting their achievements at school. The dominating
      symptom with three of these children has been aggressiveness, with two of them it
      has been social withdrawal and insecurity and one child suffered from
      psychosomatic complaints. The success of the treatment was determined by
      different target areas (symptomatic features, adaptive function, individual
      therapeutic goals, assessment of the treatment), having been assessed by
      different persons of reference (parents, teachers, therapists). According to the
      results the effectiveness of the Integrative Group Therapy with children has to
      be regarded unsatisfactory. The average effect size (averaged over all the scales
      of CBCL and TRF) amounts to 0.32. Considering only those scales where there have
      been peculiarities at the preliminary measuring, the average effect size amounts
      to 0.39. According to the individual case evaluation the treatment may be
      considered successful with one child, yet with another child a definite negative
      development has been noticed, and with four of the children no or slightly
      positive changes have been registered. The Integrative Group Therapy seems to be
      inapplicable to children with aggressive problems. In conclusion the results will
      be discussed and proposals for an improvement of the treatment are being made.

PMID- 11471424
TI  - [Dangers and possible negative effects of inpatient child and adolescent
      psychiatric treatments--recognition and prevention].
AB  - Psychiatric hospitals for children and adolescents have for a period of time many
      possibilities of impact on their patients who cannot be treated successfully in
      other conditions. However, inpatient treatment may display unwanted effects, too,
      which compromise the treatment goals. Ten possible areas of unfavourable
      collusion occurring with patients and their families will be presented. Measures
      to prevent them will be proposed. The relative lack of reliable research data on
      how inpatient treatment works and on outcome will be mentioned. The knowledge of
      emotional pitfalls pointed out help clinicians to cope with clinical problems
      arising within this area.

PMID- 11471425
TI  - Highmark feeling pressure. Chiropractors file class-action suit contending
      insurer is hoarding reserves.

PMID- 11471426
TI  - Corporate cloak and dagger. Tabloid tale of high-tech espionage fuels legal duel
      of doc-placement firms.

PMID- 11471427
TI  - A matter of antitrust? Health system's plan to acquire Ohio hospital raises
      questions.

PMID- 11471428
TI  - Separation of church and state. Catholic, secular hospital mergers face new
      hurdles as sides diverge further.

PMID- 11471429
TI  - Waiting in the lobby for money. Campaigns for new Medicare funds running slow as
      other issues take forefront.

PMID- 11471430
TI  - Coming of age. Disease management making a case for itself clinically and
      financially.
AB  - More providers are using a variety of approaches to patient care that fall under
      the nebulous term 'disease management.' Although it was slow to catch on,
      especially among physicians, interest has accelerated as both providers and
      payers see the benefits clinically and financially.

PMID- 11471431
TI  - Picking up speed. Post-acute providers trim losses, but they're still traveling a
      bumpy road.

PMID- 11471432
TI  - Volume set too high. N.J. behavioral health provider cites reimbursement woes as
      it closes clinics.

PMID- 11471433
TI  - 'Prompt payment' prompts disgruntlement. Providers find laws to hasten
      reimbursements haven't sped up health plans.

PMID- 11471434
TI  - The good guys win, for once.

PMID- 11471435
TI  - At what cost? Price tag on possible antitrust exemptions for doctors remains
      mystery.

PMID- 11471436
TI  - A thousand words. Have a heart.

PMID- 11471437
TI  - Tough love, teen death.

PMID- 11471438
TI  - Surgery. A million amazing beats. An experimental bionic heart saves a life--for
      now.

PMID- 11471439
TI  - Memory's mind games.

PMID- 11471440
TI  - [Medical certificate in psychiatry: practical aspects].
AB  - Among certificates written in psychiatry, some are obligatory, admission
      certificate, in case of automatically hospitalization or that asked by a third
      party, certificate of 48 hours: in which the psychiatrist of the admission'
      service describes the state of the patient and indicates the necessity or not to
      continue the hospitalization, monthly certificate: to justify the maintenance of
      hospitalization or to ask its end and certificate of situation be written in some
      particular circumstances. Others concern the cases of expert appraisement (in
      civilian or penal rights) or in the framework of medical controls asked by the
      employer. Other certificates are optional or customary. They could be delivered
      if asked by the patient. These considerations incite to follow scrupulously
      ethical rules and common sense when doing these certificates. Finally, The
      certificate has always to be given to the patient personally. That will be
      mentioned down of the document.

PMID- 11471441
TI  - [Autologous transfusion program].
AB  - The term autologous transfusion describes transfusion of any blood component that
      was donated by intended recipient. A recipient who serves as his or her own donor
      receives the safest possible transfusion in that the risks of transfusion
      transmitted infection and alloimmunization are eliminated. A preoperative
      autologous transfusion program provides many benefits to the donor-patient the
      blood donor center and the hospital transfusion service; requires a good
      communication between the transfusion physician and the collecting facility and
      needs a rigorous technical organization of the blood bank to ovoid the human
      errors of testing and labeling. Underutilizaton of autologous blood programs in
      our country is possibly related to a lack of awareness on the part of all the
      contributors.

PMID- 11471442
TI  - [Autologous versus homologous transfusion in cervico-fascial oncologic and ENT
      surgery].
AB  - The objective was to evaluate the interest of the normovolemic hemodilution (NVH)
      in cervico-facial oncologic and ENT surgery. It was a prospective, randomised and
      simple blind study having included A(n = 17) having benefitted before induction
      of a blood withdrawal of 6-8 ml.kg-1, substituted by an intravenous drip of
      colloid. B group (n = 21). The transfusional objective having been to assure for
      the two groups, during operative and in postoperative periods, a rate of Hb > or
      = 10 g.dl-1 and a rate of Ht > or = 30%. The two groups were comparable for the
      demographic and anesthetic characteristics, and the blood losses during operative
      period. A variation significantly more important between before and postoperative
      hemoglobin has been objectified in the group A. The infectious morbidity was
      significantly more elevated in the group A (23.5% versus 4%). The cost was
      distinctly more elevated in the hemodiluted group. The NVH doesn't seem to be an
      indication of choice in the cervico-facial and ENT oncologic surgery.

PMID- 11471443
TI  - [Atrial septum aneurysm. Report of 20 cases].
AB  - Atrial septum aneurysm (ASA) is an uncommon congenital malformation, which is
      more frequently diagnosed since the introduction of transoesophageal
      echocardiography. ASA is often involved in the etiology of cerebral and systemic
      embolic events. The purpose of our study is to determine from our experience the
      frequency, the diagnostic aspect and therapeutic modalities of ASA. We report in
      this study 20 cases of ASA collected from the echocardiographic register. The
      prevalence of this malformation is 0.08%, with a high male predominance. The mean
      age was 51 years. ASA was detected after brain embolism in 55% of cases. The
      diagnosis was established in all cases by transesophageal echocardiography,
      however only 5 cases were diagnosed by Transthoracic echocardiography. The
      patients showed favorable evolutions after a of follow up of three years.

PMID- 11471444
TI  - [Interest in treatment with subconjunctival clindamycin in toxoplasmic
      retinochoroiditis].
AB  - To demonstrate advantages of using subconjunctival injections of clindamycin in
      the treatment of toxoplasmic retinchoroiditis. METHODS: A prospective study was
      conducted in 13 patients with unilateral toxoplasmic retinochoroiditis. All cases
      were treated with subconjunctival injections of clindamycin in association with
      general corticosteroids. Mean follow-up was 7.6 months. RESULTS: Subjective
      improvement of the visual acuity was obtained in 67% during the first week.
      Cicatrization was obtained in 1.4 months on average. Recurrences were developed
      in 15% of cases. Clindamycin did not produce any general side effects, however a
      conjunctival inflammation and keratitis were observed in one case caused by an
      error in concentration of clindamycin. Subconjunctival injections of clindamycin
      provide an interesting alternative in the choice of antitoxoplasmic ocular
      therapy.

PMID- 11471445
TI  - [Subretinal neovascularization in angioid streaks].
AB  - Angoid streaks are linear crack-line dehiscences of Bruch's membrane. Choroidal
      neovascularization is the most serious complication of angioid streaks. The
      authors try to determine the incidence of neovascular macular degeneration in
      angioid streaks, their detection and treatment. A retrospective study of 26 eyes
      of 13 patients with angioid streaks was performed, 6 of whom had macular
      complications and 3 had subretinal neovascular membranes. Indocyanine green
      angiography is an adjunctive diagnostic tool in the detection of subretinal
      neovascular membranes in angioid streaks. Laser photocoagulation of choroidal
      neovascularization in angioid streaks may end the choroidal neovascularization
      and help stabilize visual acuity.

PMID- 11471446
TI  - [Influence of socio-professional factors on absenteeism of hospital personnel].
AB  - The goal of this work is to analyze the different reasons of absenteeism in
      hospital and to identify the socioprofessional characteristics of absentees, what
      would permit to guide a strategy on modes and content of a preventive action. The
      adopted methodology is a retrospective descriptive investigation carrying on
      absenteeism of the personnel working in academic hospital Farhat Hached of Sousse
      (Tunisia) during 1997. So, on the 1433 salaried employees, 1028 (71.7%), left
      once or more for different reasons. The global absenteeism rate is 4.03% and the
      mean absence by agent is equal to 14.7 days. Among the absences motives, illness
      predominate extensively with 55% of the whole. Maternity and postnatal leave
      constitute 30%, 8% for "Industrial accidents" of work stops. Whatever is the
      reason, we observes more absent women than absent men. This survey shows the
      importance of socioprofessional factors in genesis of absenteeism and, to reduce
      the problem, the necessity to improve conditions of work, moreover in his
      ergonomic, social and psychological aspects.

PMID- 11471447
TI  - [Pulmonary scintigraphy with MAA-Tc 99m perfusion in the diagnosis of pulmonary
      embolism].
AB  - Perfusion lung scintigraphy is vital to guide the diagnosis even without a
      ventilation scintigraphy. A customised strategy could be useful to optimise the
      use of perfusion scintigraphy when not coupled with a ventilation scintigraphy.
      We report about a retrospective study on 300 patients received in our department
      for suspected lung migrations. The patients underwent a perfusion scintigraphy
      only: a normal scintigraphy would discard the diagnosis when achieved between 6
      and 72 hours after the accident. On the other hand, the evidence of one or two
      perfusion defects would allow to maintain the pulmonary embolism suspicion and
      establish an effective heparinic treatment. A second control comparative
      scintigraphy, a few weeks after the first one, very often confirms the diagnosis,
      allows the assessment of the heparinotherapy and if necessary, indicate to stop
      it.

PMID- 11471448
TI  - [Death of one fetus in multiple pregnancies during the second and third
      trimesters. Maternal-fetal complications].
AB  - The authors report 7 cases of death of one foetus during multiples pregnancies in
      107 pregnancies during the second and the third quarter. The rate is 6.54%. Five
      cases are complicated by toxaemia which increased the caesarean rate. The
      placenta is monochorial in 4 cases. The hemostasis check up shows a drop of
      fibrinogen and the rate of thrombin, which normalised after delivery. One patient
      developed in septicaemia after caesarean delivery. Concerning the surviving
      foetus: 5 of them had en intra uterine under development, 2 of them were
      premature and one developed an encephalopathy.

PMID- 11471449
TI  - [Guillain-Barre syndrome in children. Report of 39 cases].
AB  - The authors report a retrospective study of 39 cases of Guillain-Barre syndrome
      in children. Including 23 boys and 16 girls. The mean age was 4 years (14 months
      to 10 years). A history of infection preceded the polyradiculoneuritis in 75% of
      cases. The mean duration of extensive phase and of the maximum paralysis was 10
      days. A severe respiratory involvement was observed in 9 children and cranial
      nerve paralysis in 8 children. An early raised cerebrospinal fluid protein
      concentration was found in 95%. Electrodiagnostic studies, performed in 37
      patients, showed nerve conduction velocity slowing in all cases. 28 children
      (73%) recovered clinically, 8 patients (20%) had residual deficits and 3 patients
      (7%) died.

PMID- 11471450
TI  - [Epidemiologic aspects of common gastrointestinal food toxin infections in the
      Bizerte region based on surveillance center analyses from 1994 to 1999].
AB  - The Common Food Toxin Infections has been subject of constant and exhaustive
      supervision watch over since 1994 in Bizerta. 77 centers in total has been
      recorded during the six last years (1994 to 1999) and have shown 738 patients.
      The evolution of incidental rate declared has been considered by annual
      fluctuations with extreme rates as 11.2 for 10,000 inhabitants in 1995 and 41.5
      for 10,000 inhabitants in 1999. The classic season peak each year, and so 58.4%
      of centers has been notified during the months of July, August and September. The
      average size of centers is 9.5 persons with an extension of 02 to 40 persons. One
      death has been deplored a weak spreading rate of 0.14%. The hospitalization
      recommended for 106 patients (14.4%). About three quarters of the centers has
      been concerned by the familial. The cooked food is being at the top of
      contaminating food (49.3%).

PMID- 11471451
TI  - [Isolated, spontaneous hematoma of the kidney. Report of 2 cases].
AB  - Spontaneous hematoma under the renal capsula is a rare pathology. The authors
      report two cases with one male and one female aged respectively of 50 and 63
      years. The symptomatology is presented by right renal aches associated with
      repetitive and total hematuria in male and atypical abdominal aches in female.
      The radiological explorations (IVP, renal sonography and Computered Tomography)
      had conclude in a renal cancer in the two cases. The diagnosis is made by the
      pathologic study. Some etiology may be searched such as malignant tumor, an
      angiomyolipoma, vascular abnormalities and disturbance to the hemostasis. If no
      etiology is find, a nephrectomy or a simple supervision can be discussed.

PMID- 11471452
TI  - [Menetrier's disease: a case report].
AB  - Menetrier's disease is an uncommon reason of hypertrophic gastropathy. The
      diagnosis is suspected when clinic, endoscopic and radiologic criteria are
      associated and is confirmed by histologic features which are a cryptric
      hyperplasia atrophy of gland of the fundus and an hypertrophy of the mucosa. The
      main complications of this disease are neoplasia and cachexia. The treatment of
      Menetrier's disease is first medical. Chirurgical treatment is indicated when
      bleeding or neoplasia occurred. In this paper, we report the case of patient who
      is 41 years old which, in spite of some therapeutic problems is in conformity
      with literature.

PMID- 11471453
TI  - An improved GC/MS-based procedure for the quantitation of the isoprostane 15-F2t
      IsoP in rat plasma.
AB  - This article describes a procedure for the quantitation of the isoprostane 15-F2t
      IsoP (9a,11a,15S-trihydroxy-(8b)-prosta-5Z,13E-dien-1-oic acid [CAS#27415-26-5]
      formerly known as 8-epi-PGF2a or 8-iso-PGF2a, and also as iPF2a-III). We have
      combined features from several earlier methods for 15-F2t-IsoP and
      prostaglandins, and identified and modified those steps that may lead to poor
      recoveries. The resulting protocol is precise and reliable, and was validated by
      a blind time-course study of plasma levels in rats treated with 120 and 1200 mg
      CCl4/kg body weight. Plasma levels of 15-F2t-IsoP, as measured according to the
      procedure described above, are good indicators of acute oxidative stress as
      induced by CCl4. The precision of the measurements allows detection of elevated
      plasma 15-F2t-IsoP levels as long as 16 h after an acute exposure of 120 mg
      CCl4/kg body weight, and 2 h after an exposure of 1 mg CCl4/kg body weight. The
      results of this low-dose, pilot study suggest that this method has sufficient
      analytical precision to allow the detection of the small changes in plasma
      isoprostane levels, which result from chronic and/or lower-level exposures to
      agents causing oxidative stress.

PMID- 11471454
TI  - Molecular techniques for the investigation of meningococcal disease epidemiology.
AB  - Meningococcal disease remains a major cause of childhood morbidity and mortality
      world wide and no comprehensive vaccine is available against the causative
      organism, Neisseria meningitidis. Molecular studies of the diversity of this
      bacterium have provided a number of key insights into its biology, which have
      implications for control of meningococcal disease. These have included the
      identification of hyperinvasive lineages and the correlation of genetic type with
      antigenic type and disease epidemiology. In practical terms, such studies have
      enabled the application of DNA-based technologies in the development of improved
      methods for diagnosis and epidemiological monitoring. These data are of especial
      importance with the current, and ongoing, development and introduction of new
      meningococcal vaccines.

PMID- 11471456
TI  - Atomic force microscopy measurements. Measurements of binding strength between a
      single pair of molecules in physiological solutions.
AB  - Atomic force microscopy (AFM) measurements of intermolecular binding strength
      between a single pair of complementary cell adhesion molecules in physiological
      solutions provided the first quantitative evidence for their cohesive function.
      This novel AFM based nanobiotechnology opens a molecular mechanic approach for
      studying structure to function related properties of any type of individual
      biological macromolecules. The presented example of Porifera cell adhesion
      glyconectin proteoglycans showed that homotypic carbohydrate to carbohydrate
      interactions between two primordial proteoglycans can hold the weight of 1600
      cells. Thus, glyconectin type carbohydrates, as the most peripheral cell surface
      molecules of sponges (today's simplest living Metazoa), are proposed to be the
      primary cell adhesive molecules essential for the evolution of the
      multicellularity.

PMID- 11471455
TI  - Animal models of inherited complement deficiency.
AB  - The initial description of murine strains deficient in complement component C5
      has been followed by the recognition in a range of animal species of a variety of
      natural complement component deficiencies, many of which have been characterized
      at the molecular level. The use of such species in inflammatory and infectious
      experimental models has led to significant progress in understanding the role of
      specific complement factors (and pathways) in disease pathogenesis. Deficiencies
      of early complement factors are characterized by impairment of immune response,
      possibly due to defective processing of immune complexes. Complete (but not
      partial) deficiency of the central component C3 predisposes affected animals to
      significant risk of infection and renal disease. Studies in species deficient in
      the terminal pathway component C6 are particularly relevant for investigating the
      pathogenetic role of the terminal membrane attack complex (MAC), implicating it
      as a causative agent in diverse inflammatory insults such as reperfusion injury,
      glomerular damage, and xenograft hyperacute rejection. Further investigations in
      such naturally deficient strains, added to results derived from studies in
      knockout animals, are likely to expand our understanding of the role of the
      activated complement system in experimental inflammatory disease, with
      significant potential implications for the treatment of human disease.

PMID- 11471457
TI  - Evaluating phenotype and genotype of drug-resistant strains in herpesviruses.
AB  - The isolation of drug-resistant strains of herpesviruses, including Herpes
      Simplex Virus type I (HSV-1) and type 2 (HSV-2), Varicella-Zoster Virus (VZV),
      and cytomegalovirus (CMV), has been reported with increasing frequency in
      immunocompromised patients and is a matter of major concern. Determination of
      antiviral drug susceptibilities is a prerequisite for the management of drug
      resistant herpesvirus infections. Phenotyping studies should be correlated with
      genotyping, i.e., characterization of the mutations in the target genes. The
      isolation of drug-resistant virus in the laboratory and the determination of
      their phenotype and genotype may be useful to clarify the mechanisms of selective
      drug action. We describe here the procedures used for in vitro selection of drug
      resistant herpesvirus mutants and the determination of their patterns of drug
      susceptibility. The subcloning of the HSV-1 DNA polymerase gene is described as
      an example of the methodology followed to determine the mutation(s) in the drug
      target viral gene that are associated with the resistant phenotype. To avoid the
      introduction of mutations by PCR amplification, all subcloning experiments were
      executed directly on viral DNA. Viral DNA was prepared from each plaque-purified
      viral strain and a 3.4 kb BamHI fragment containing 87% of the HSV-1 DNA
      polymerase gene coding region was purified and further digested with SacI; the
      two resulting fragments were subcloned into pU18 and propagated in Escherichia
      coli. Plasmid DNA was isolated and the inserts were sequenced using
      dideoxynucleotide chain termination method with T7 DNA polymerase and Taq DNA
      polymerase in an automated laser fluorescent DNA sequencer. pUC/M13 reverse,
      universal primers and oligonucleodite primers based on the wild-type virus
      sequence were used. The nucleotide sequences of the DNA polymerase genes of the
      different mutants was then compared with the nucleotide sequence of the wild-type
      HSV-1 KOS strain.

PMID- 11471458
TI  - Microinjection technique used to study functional interaction between p53 and
      hepatitis B virus X gene in apoptosis.
AB  - Microinjection of expression vectors into cultured cells has been utilized to
      study functional interaction of p53 and the hepatitis B virus HBx gene in
      apoptosis. This approach allows us to determine protein-protein interactions in
      primary cultured human cells at a single cell level, including fibroblasts,
      mammary epithelial cells, renal epithelial cells, and hepatocytes. In principle,
      this approach can be used to study functional interaction of p53 and any gene
      that is either pro- or anti-apoptotic. The use of primary cultured human cells
      minimizes ambiguous results associated with immortalized or tumorigenic cell
      lines. Moreover, it is an easy and effective way to introduce genes of interests
      into primary human cells with defined genetic defects, thereby facilitating the
      delineation of genetic pathways.

PMID- 11471460
TI  - Professionals or technicians? The importance of enhancing patient trust.

PMID- 11471459
TI  - A method for accurate detection of translocation junctions in Ewing family of
      tumors.
AB  - The Ewing family of tumors (ET) generally contain translocations involving the
      EWS gene and the FLI or ERG genes. Identification of the translocation confirms
      the diagnosis of ET. Currently, diagnosis of the translocation is made by several
      methods. In general, these methods require different primer sets for amplifying
      different translocations and subsequent efforts to identify the amplified
      product. The need to employ different sets of primers to amplify different
      translocation junctions presents some limitations. We have developed a method
      based on PCR with consensus primers followed by direct automated sequencing of
      the amplified product. With this method we have correctly determined known as
      well as unknown ET-associated EWS-FLI and EWS-ERG translocations in appropriate
      specimens. Use of our consensus primers eliminates the need for separate PCRs to
      amplify EWS-FLI and EWS-ERG translocation junctions, and because direct
      sequencing is used for confirming the identity of the amplification product, the
      accuracy of detection becomes 100%. The method might also accurately diagnose ET
      associated translocations other than EWS-FLI and EWS-ERG translocations.

PMID- 11471461
TI  - An analysis of factors determining the use of breast conserving surgery for
      treating early-stage breast cancer.
AB  - To determine the trend of breast conserving surgery (BCS) in West Virginia and to
      identify patient, hospital and surgeon factors associated with use of BCS, we
      conducted a study of all cases of Stage I and II invasive breast cancer treated
      surgically in West Virginia from 1991 through 1995 (N = 2411). These records were
      obtained from the State Cancer Registry. Multiple logistic regression was used to
      generate odds ratios (or) and 95% confidence intervals (CI) to determine factors
      associated with BCS. Our results showed the rate of BCS increased from 25% in
      1991 to 37% in 1994 and 33% in 1995, with an overall rate of 33%. Multiple
      logistic regression identified the following factors associated with BCS: tumor
      size less than 1 cm (or = 1.47, 95% C1 = 1.4, 1.5), hospital bed size > 300 beds
      (or = 1.3, 95% C1 = 1.05-1.6) and a surgeon who had graduated from medical school
      since 1981 (or = 1.2, 95% C1 = 1.0, 1.36). We conclude the rate of BCS in West
      Virginia still remains low and that the women least likely to have BCS were women
      with tumors > 2 cm treated at small hospitals by older physicians.

PMID- 11471462
TI  - Interscapulothoracic amputation.
AB  - Interscapulothoracic or "forequarter" amputation is an ablative surgical
      procedure that is physically mutilating and potentially psychologically
      traumatic. We have performed this operation on five occasions over the past 30
      years for various indications: osteosarcoma, metastatic breast cancer, skin
      cancer and electrical burn. The operation was originally described by Berger in
      1883 and was intended for use in traumatic injuries. Currently, its use is
      generally reserved for cases of ascending infection and for curative purposes in
      cases of bone and soft tissue sarcoma, but may be used for palliation.

PMID- 11471463
TI  - Small cell neuroendocrine carcinoma of the urinary bladder: case report of a rare
      primary tumor.
AB  - Primary small cell neuroendocrine carcinoma of the bladder is a rare condition,
      with fewer than 140 cases having been reported. It is an aggressive tumor with an
      average five-year survival rate of less than 10 percent as cited by multiple case
      reports. We report a 73-year-old white woman with primary small cell
      neuroendocrine carcinoma of the bladder who was treated with radical cystectomy
      and adjuvant cisplatin/etoposide-based chemotherapy.

PMID- 11471464
TI  - Physical activity and osteoporosis: disparities between knowledge and practice.
AB  - Osteoporosis and osteoporosis-related conditions are national health priorities,
      and physical activity has been associated with a reduction of osteoporosis risk
      factors (i.e., increased bone mineral density and decreased falls). Our study
      examined the disparity between awareness of physical activity as an osteoporosis
      prevention strategy and the quantity and quality of physical activity performed.
      Results indicate that most individuals view physical activity as an important
      prevention strategy. However, few participants are engaged in physical activity
      which meets current public health recommendations despite their awareness of
      physical activity health benefits. Barriers to regular exercise are discussed as
      well as promising approaches to reducing barriers through alterations to physical
      and social environments.

PMID- 11471465
TI  - Western Nile Virus: a new public health concern.
AB  - In August 1999, the Western Hemisphere was introduced to the Western Nile Virus
      for the first time in recorded history. Many states have implemented screening
      and identification protocols for this previously rare virus. Western Nile Virus
      (WNV) is a member of the Flaviviridae family and it is transmitted by the Culex
      pipiens mosquito, although other mosquito species have also been implicated in
      carrying the virus. Human infection with West Nile Virus can range from
      asymptomatic to full blown encephalitis with permanent neurological impairment
      and death. Treatment should be aimed at detecting early signs of infection. The
      Western Nile Virus must be tracked and detected early, so that future outbreaks
      can be prevented.

PMID- 11471466
TI  - New WV Board of Medicine Policy Statement on pain management at the end of life.

PMID- 11471467
TI  - Joint policy statement on pain management at the end of life.

PMID- 11471468
TI  - West Virginia Department of Health and Human Resources information for physicians
      -West Nile Virus.

PMID- 11471469
TI  - National cholesterol-management guidelines call for aggressive therapy.

PMID- 11471470
TI  - Scam artists target hospitals for biotech product.

PMID- 11471471
TI  - New drug targets genetic malfunction in chronic myeloid leukemia.

PMID- 11471472
TI  - States forge ahead with medical marijuana despite federal ruling.

PMID- 11471473
TI  - Management of antiretroviral therapy focuses on boosting adherence, minimizing
      toxicities.

PMID- 11471474
TI  - AHA survey confirms health care work-force shortage.

PMID- 11471475
TI  - Medicare, Medicaid agency given self-evident name.

PMID- 11471476
TI  - Health illiteracy interferes with care.

PMID- 11471477
TI  - Pharmacologic options for the treatment of obesity.
AB  - Past and current drug therapies for weight loss are discussed. More than 50% of
      Americans can be categorized as overweight or obese. Obesity is associated with
      increased mortality and with comorbidities such as hypertension, hyperglycemia,
      dyslipidemia, coronary artery disease, and certain cancers. According to
      guidelines for identification, evaluation, and treatment of obesity, patients
      with a body mass index (BMI) of > or = 30 kg/m2 should attempt to lose weight.
      Patients with a BMI of > or = 25 kg/m2 plus two or more risk factors or patients
      with an excessive waist circumference plus two or more risk factors should also
      attempt to lose weight. The initial goal is a 10% weight reduction in six months
      achieved through lifestyle changes. If lifestyle changes alone are not effective,
      then drug therapy may be indicated. Pharmacotherapeutic options for obesity have
      decreased over the past few years. Fenfluramine, dexfenfluramine, and
      phenylpropanolamine have been withdrawn because of severe adverse effects,
      leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA
      approved labeling. Phentermine has been shown to cause a 5-15% weight loss if
      given daily or intermittently. Compared with sibutramine and orlistat,
      phentermine is cheaper, and specific formulations allow once-daily
      administration. However, phentermine is indicated only for short-term treatment,
      and tolerance often develops. Common adverse effects associated with phentermine
      are dry mouth, insomnia, increased blood pressure, and constipation. Sibutramine
      increases norepinephrine and serotonin levels in the CNS and should not be taken
      with many antidepressants because of the risk of increased norepinephrine and
      serotonin levels. Its use is also contraindicated in patients with cardiovascular
      disease. Orlistat is not systemically absorbed; therefore, it does not cause the
      systemic adverse effects or drug interactions of phentermine and sibutramine.
      Orlistat has a cholesterol-lowering effect not seen with other diet medications.
      However, the three-times-daily administration and frequent gastrointestinal
      effects limit its use. Sibutramine, phentermine, and orlistat have both positive
      and negative properties. Choosing among the medications will depend on concurrent
      disease states and medications, ease of administration, and cost.

PMID- 11471478
TI  - Outcomes assessment of clinical pharmacy services in a psychiatric inpatient
      setting.
AB  - The effects of psychiatric pharmacy services on clinical outcomes of acute care
      psychiatric inpatients were studied. Patients recruited at a state psychiatric
      facility during phase 1 (October 1996-March 1997) served as the control group and
      received only traditional centralized pharmaceutical services and physician
      requested psychiatric pharmacotherapy consultations. Patients recruited during
      phase 2 (May-December 1997) received intensive psychiatric pharmacy services and
      served as the experimental group. Pharmaceutical services during phase 2 included
      attending treatment team meetings, performing baseline assessments and weekly
      reviews, providing pharmacotherapy recommendations, obtaining medication
      histories, reviewing drug administration records daily, monitoring for adverse
      drug reactions, conducting medication education classes, and counseling patients
      before discharge. Outcome variables included clinical response determined with
      objective rating scales, cost of care, length of stay, adverse events, rate of
      acceptance of recommendations, patient compliance with the first clinic visit
      scheduled after discharge, quality of life, and patient satisfaction. Data were
      analyzed for 48 patients in the control group and 45 patients in the experimental
      group. There were no significant differences between the two groups with respect
      to age, sex, duration of illness, number of hospitalizations, and number of
      months since the last hospitalization. Patients in the experimental group showed
      significant improvements in clinical response and drug-induced extrapyramidal
      symptoms compared with the controls and were highly satisfied with the
      pharmaceutical services they received. Medication costs did not differ
      significantly, and length of stay was about 29 days for each group. The provision
      of clinical pharmacy services provided to inpatients in an acute care psychiatric
      facility was associated with improvements in rating-scale scores for clinical
      response and for drug-induced extrapyramidal symptoms.

PMID- 11471479
TI  - Potential risks and prevention, Part 1: Fatal adverse drug events.
AB  - Potential risk factors for and the preventability of fatal adverse drug events
      (ADEs) were studied. Case reports of ADEs published in Clin-Alert during 1976-95
      were the source of information on fatal ADEs, Patient, drug, and event variables
      were identified, and the causality, predictability, and preventability of each
      case were assessed. Data were entered into a relational database for analysis.
      The data indicated 447 cases involving a fatal ADE. Ten percent of the fatal ADEs
      were assessed as definite, 46% as probable, and 44% as possible. Fatal-ADE
      frequency increased with age. Forty-five percent of the patients were 40-69 years
      of age, and 40% were healthy. Central-nervous-system agents, antineoplastics,
      antimicrobials, and cardiovascular agents accounted for 69% of the deaths. Only
      33% of patients received more than the usual dosage. Many of the suspected drugs
      could have been monitored with blood level tests but were not, and baseline
      testing of critical blood count and liver and renal function was often not
      performed. The most common causes of death were hepatitis, hepatic failure,
      cardiopulmonary arrest, overdose, and agranulocytosis. ADE types were distributed
      as adverse drug reactions (58%), allergic reactions (19%), medication errors
      (17%), and drug interactions (6%). Sixty-eight percent of the fatal ADEs were
      judged to have been preventable; of these, a pharmacist could have prevented 57%.
      Litigation was reported for 14% of the fatal-ADE cases; judgments and settlements
      averaged $1.1 million. A review of published case reports of ADEs for 1976-95
      yielded information on possible risk factors for fatal ADEs and on which events
      may have been preventable.

PMID- 11471480
TI  - Potential risks and prevention, Part 2: Drug-induced permanent disabilities.
AB  - Potential risk factors for and the preventability of drug-induced permanent
      disabilities were studied. Case reports of adverse drug events (ADEs) published
      in Clin-Alert during 1978-97 were the source of information on drug-induced
      permanent disabilities. Patient, drug, and event variables were identified, and
      the causality, predictability, and preventability of each case were assessed.
      Data were entered into a relational database for analysis. The data indicated 227
      cases of drug-induced permanent disabilities. Twenty-three percent of the cases
      were assessed as definite, 47% as probable, and 30% as possible. Twenty-nine
      percent of the patients were less than 10 years old, and 36% were considered
      healthy. The drug categories most commonly associated with a drug-induced
      permanent disability were antimicrobials, vaccines, central-nervous-system
      agents, and antineoplastics. About half of the patients received more than the
      usual dosage. The most common permanent disabilities were brain damage,
      blindness, tardive dyskinesia, deafness, quadriplegia, and hearing loss. Event
      types were distributed as medication errors (55%), adverse drug reactions (43%),
      and drug interactions (2%). Eighty-four percent of the drug-induced permanent
      disabilities were judged to have been preventable; of these, a pharmacist could
      have prevented 40%. Litigation was reported for 56% of the cases of drug-induced
      permanent disability; judgments and settlements averaged $4.3 million. A review
      of published case reports of ADEs for 1978-97 yielded information on possible
      risk factors for drug-induced permanent disabilities and on which events may have
      been preventable.

PMID- 11471481
TI  - Interpreting the findings of the IMPROVE study.
AB  - Various findings of the Impact of Managed Pharmaceutical Care on Resource
      Utilization and Outcomes in Veterans Affairs Medical Centers (IMPROVE) study are
      reviewed. Suggestions for future methodologies that will enhance this study are
      discussed. The IMPROVE study is one of the largest pharmaceutical care studies
      conducted. Although it was an intervention study that examined global outcomes
      following management by pharmacists, it was designed as an effectiveness study.
      Several new practice and research methods were developed, including a method to
      identify patients at high risk for drug-related problems utilizing pharmacy
      databases, a method to identify chronic diseases using pharmacy databases, a
      method to evaluate the structure and process for delivering pharmaceutical care
      in Veterans Affairs medical centers (VAMCs), and guidelines for providing care to
      patients in the IMPROVE study. Nine VAMCs participated in the study, and 1054
      patients were randomized to either an intervention group (n = 523) or a control
      group (n = 531). Pharmacists documented a total of 1855 contacts with the
      intervention group patients and made 3048 therapy-specific interventions over the
      12-month study period. There was no meaningful difference in patient satisfaction
      or quality of life in the two groups. Selected disease-specific indicators found
      an improved rate of measurement of hemoglobin A1c tests and better control of
      total and low-density-lipoprotein (LDL) cholesterol levels in the intervention
      group compared with the control group. Total health care costs increased in both
      groups over the 12-month period. The mean increase in costs in the intervention
      group was $1020, which was lower than the control group's value of $1313. The
      lessons learned from the IMPROVE study suggest to future investigators how to
      study and measure the effects of clinical pharmacy services on patient outcome.

PMID- 11471482
TI  - Cost-effectiveness of proton-pump inhibitors for maintenance therapy of erosive
      reflux esophagitis.
AB  - The relative cost-effectiveness of proton-pump inhibitors (PPIs) in the
      maintenance therapy of erosive reflux esophagitis was studied. Decision analysis
      was used to model the cost-effectiveness of PPIs on the basis of clinical trial
      results. Management decisions in the model were based on published U.S.
      guidelines and recommendations. Probability estimates were derived from a
      systematic review of the literature. The model's base-case scenario compared
      rabeprazole, lansoprazole, and omeprazole for the prevention of symptom
      recurrence over one year. Meta-analyzed estimates of efficacy were derived from
      trials by using a generalized logistic regression model with random effects.
      Medical costs for hospitalization, procedures, and office visits reflected 2000
      Medicare payment; drug costs were based on 2000 average wholesale prices. Average
      costs per patient were comparable among the PPIs (rabeprazole, $1414;
      lansoprazole, $1671; and omeprazole, $1599). Rabeprazole prevented symptom
      recurrence in 86% of rabeprazole recipients, versus 68% for lansoprazole and 81%
      for omeprazole, and yielded the lowest average cost-effectiveness ratio
      (rabeprazole, $1637 per recurrence prevented; lansoprazole, $2439; and
      omeprazole, $1968). The model was robust to changes in key variables. When
      evaluated by decision analysis over a wide range of assumptions, rabeprazole was
      comparable to other PPIs in terms of cost and offered improved effectiveness for
      maintenance therapy of erosive reflux esophagitis.

PMID- 11471483
TI  - Robley Evans and what physics can do for medicine.
AB  - When asked, in 1936 by J. Howard Means, Chief of Medicine at Massachusetts
      General Hospital, whether radioiodine could be produced for thyroid studies, Karl
      T. Compton, President of the Massachusetts Institute of Technology, referred the
      question to Robley Evans of the physics department. In response, Evans formed a
      team from the fields of physics and medicine that produced 128I for animal
      studies and, subsequently on a cyclotron dedicated to medical purposes, 130I for
      human uptake measurements and the treatment of hyperthyroidism. Much of what we
      have learned about iodine kinetics and the radioiodine therapy of Graves's
      disease stems from these early seminal reports. The cooperation between
      physicists and physicians that made their accomplishments possible stands as a
      model example for interdisciplinary collaboration.

PMID- 11471484
TI  - Induction of CA125-specific B and T cell responses in patients injected with MAb
      B43.13--evidence for antibody-mediated antigen-processing and presentation of
      CA125 in vivo.
AB  - The murine monoclonal anti-CA125 antibody MAb-B43.13 has previously been
      administered as an immunoscintigraphic agent in order to monitor recurrence of
      ovarian cancer in patients, and a long-term follow-up demonstrated a survival
      benefit for these patients. The clinical benefit was initially attributed to the
      activation of the idiotypic network. The objective of this study was to
      investigate the role of CA125-MAb-B43.13 immune complex formation on the
      induction of CA125-specific immune responses. Analysis of patient serum samples
      from pharmacokinetic studies demonstrated that the antibody forms immune
      complexes with CA125 in circulation within 30 minutes of injection. Induction of
      humoral and cellular anti-CA125 responses correlated with the amount of
      circulating CA125 antigen present at time of antibody injection. Subsequent to
      the injection of MAb-B43.13, the patients generated anti-CA125 antibodies that
      were directed against various epitopes on the antigen and were not restricted to
      the specific epitope recognized by MAb-B43.13. The generation of CA125-specific B
      and T cell responses after MAb-B43.13 injection correlated with improved
      survival. The influence of circulating CA125 for the induction of CA125-specific
      immune responses and the multi-epitopic nature of the human anti-CA125 antibodies
      suggest that the majority of these antibodies were not induced via the idiotypic
      network but by the autologous antigen itself. Since antibody and T cell responses
      to CA125 were not present before injection of MAb-B43.13, it is hypothesized that
      complex formation of MAb-B43.13 with circulating antigen triggers the induction
      of CA125-specific immune responses.

PMID- 11471485
TI  - Short-term tumor cell lines from breast cancer for use as autologous tumor cell
      vaccines in the treatment of breast cancer.
AB  - OBJECTIVE: We tried to establish short-term cultures of autologous tumors from
      patients with breast carcinoma for potential use as active specific immunotherapy
      (i.e., autologous vaccine) after resection of primary breast cancer, and/or for
      the treatment of metastases. METHODS: Between 10/90 and 12/99 the cell biology
      laboratory of the Hoag Cancer Center attempted to establish short-term tumor cell
      lines from 115 breast cancer specimens from 56 primary breast lesions, 17
      axillary nodes, 14 other lymph node/soft tissue sites, 10 chest wall recurrences,
      and 6 thoracentesis of malignant pleural effusions. Success was defined by growth
      of 5 x 10(7) viable cells whose malignant nature and breast cancer origin was
      confirmed by histology of the submitted tissue, cell morphology and antigenic
      phenotyping. Variables associated with successful growth of short-term cell lines
      were examined. RESULTS: Expansion to 5 x 10(7) cells was achieved for only 8/115
      samples [7%] including two from chest wall recurrences, and one each from a
      supraclavicular node, an umbilical node, liver, omentum, and pleural fluid. Two
      of the successful cell lines were established from tissue that originally had
      been cryopreserved; the others were initiated from fresh tumor. The success rate
      was better from regional/distant metastases 7/55 (13%) compared to primary tumors
      1/56 (1.8%) (p = 0.063). The success rate for tumors harvested at Hoag Hospital
      was 4/97 (4%) compared to 4/14 from (31%) distant sites, but all but one of the
      tumors from a distant geographic site was a metastatic lesion. Tumor cell lines
      were successfully established from metastatic lesions ranging in size from < 1.0
      g to 19 g. Four patients were treated with their autologous vaccine in the
      setting of chemotherapy-refractory metastatic disease without any significant
      toxicity. CONCLUSIONS: We were unable to establish short-term cell lines for most
      patients with primary or metastatic breast cancer using this methodology.
      However, two long-term cell lines have been established and characterized.
      Treatment with the autologous irradiated cell product was not associated with
      acute toxicity.

PMID- 11471486
TI  - Apoptosis-related gene and protein expression in human lymphoma xenografts (Raji)
      after low dose rate radiation using 67Cu-2IT-BAT-Lym-1 radioimmunotherapy.
AB  - Despite low radiation dose rates, radioimmunotherapy (RIT) has proven
      particularly effective in the treatment of malignancies, such as lymphoma.
      Apoptosis has been suggested to be a major mechanism for cell death from
      continuous low-dose rate radiation from radioimmunotherapy. The goal of this
      study was to examine Raji lymphoma xenografts for induction of apoptosis and
      modulation of apoptosis-related gene and protein expression in response to 67Cu
      2IT-BAT-Lym-1 RIT. In preclinical and clinical trials, 67Cu-2IT-BAT-Lym-1 has
      shown an exceptionally long tumor residence time associated with substantial
      cumulated radiation doses. The Raji model mirrors human lymphomas that have
      mutant p53 and increased BCL2 expression. Untreated athymic BALB/c nu/nu mice and
      mice treated with 400 micrograms Lym-1, or 335-500 microCi 67Cu on less than 400
      micrograms Lym-1 antibody, were observed for toxicity and response over 84 days.
      Subgroups of 4-5 mice were sacrificed at 3, 6 and 24 h after therapy so that
      tumors could be examined for poly(ADP-ribose) polymerase (PARP) and DNA ladder
      evidence for apoptosis and for BCL2, p53, p21, GADD45, TGF-beta 1 and c-MYC gene
      and protein expression. Untreated tumors had little evidence of apoptosis and Lym
      1 had no effect on apoptosis or gene expression. 67Cu-2IT-BAT-Lym-1 RIT induced
      an overall response rate of 50% with tolerable toxicity, and 29% of the tumors
      were cured at cumulated tumor radiation doses of about 1800 cGy. Apoptosis was
      greatly increased in the RIT treated Raji xenografts as evidenced by cleavage of
      PARP to the characteristic 85 kD fragment at 3 and 6 h and by the DNA cleavage
      pattern. BCL2 gene and protein expression were substantially decreased at 3 and
      24 h, respectively, after 67Cu-2IT-BAT-Lym-1 RIT despite only modest cumulated
      radiation doses (56 cGy at 3 h). Evidence for apoptosis preceded tumor regression
      by 4-6 days. In these therapy-resistant, human lymphoma tumors treated with 67Cu
      2IT-BAT-Lym-1, apoptosis was convincingly demonstrated to be a major mechanism
      for the effectiveness of RIT and occurred by p53-independent mechanisms.

PMID- 11471487
TI  - Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients:
      phase I study and preliminary therapeutic results.
AB  - The aim of this study was to determine the maximum-tolerated dose, of a pre
      targeting three-step (3-S) method employing 90Y-biotin in the locoregional
      radioimmunotherapy (RIT) of recurrent high grade glioma, and to investigate the
      antitumor efficacy of this new treatment. Twenty-four patients with recurrent
      glioma underwent second surgical debulking and implantation of a catheter into
      the surgical resection cavity (SRC), in order to introduce the
      radioimmunotherapeutic agents [biotinylated monoclonal antibody (MoAb), avidin
      and 90Y-biotin]. Eight patients with anaplastic astrocytoma (AA) and 16 patients
      with glioblastoma (GBM) were injected with biotinylated anti-tenascin MoAb (2
      mg), then with avidin (10 mg; 24 h later) and finally 90Y-biotin (18 h later).
      Each patient received two of these treatments 8-10 weeks apart. The injected
      activity ranged from 0.555 to 1.110 GBq (15-30 mCi). Dosage was escalated by
      0.185 GBq (5 mCi) in four consecutive groups. The treatment was well tolerated
      without acute side effects up to 0.740 GBq (20 mCi). The maximum tolerated
      activity was 1.110 GBq (30 mCi) limited by neurological toxicity. None of the
      patients developed hematologic toxicity. In three patients infection occurred
      around the catheter. The average absorbed dose to the normal brain was minimal
      compared with that received at the SRC interface. At first control (after 2
      months), partial (PR) and minor (MR) responses were observed in three GBM (1 PR;
      2 MR) and three AA patients (1 PR; 2 MR) with an overall objective response rate
      of 25%. Stable disease (SD) was achieved in seven GBM and five AA patients (50%).
      There was disease progression in six GBM patients (25%), but in none of the AA
      patients. At the dosage of 0.7-0.9 GBq per cycle, locoregional 3-S-RIT was safe
      and produced an objective response in 25% of patients. Based on these encouraging
      results, phase II studies employing 3-S-RIT soon after first debulking are
      justified.

PMID- 11471488
TI  - Status of radioimmunotherapy in the new millennium.
AB  - This synopsis attempts to summarize progress made in radioimmunotherapy (RIT) by
      the end of the 20th century addressing the problems, possible solutions, and
      recent developments. The reduction of minimal residual disease in an adjuvant
      setting appears to be a feasible goal for RIT utilizing short-range alpha
      emitters. RIT has been more successful in the radiosensitive hematologic
      malignancies, for example lymphomas and leukemias as compared with small solid
      tumors. Several radiopharmaceuticals seem near approval for RIT in patients with
      non-Hodgkin's lymphoma (NHL) as therapeutic responses, including complete
      responses, are common. Obstacles to successful RIT have been recognized and
      strategies to overcome these hurdles and to improve efficacy are continuously
      being developed resulting in encouraging outcome particularly with locoregional
      routes of administration in solid tumors. Systemic RIT for solid tumors will need
      manipulating the tumor-host to improve the tumor uptake and retention of
      radioimmunoconjugates (RICs). The utilization of radiometals, stable chelators,
      biodegradable linkers and bone marrow transplantation should be able to deliver
      the radiation dose required for successful treatment. In conjunction with
      additional synergistic agents, RIT is likely to have a great impact on the
      treatment of solid tumors. The ability to generate new constructs, such as
      bivalent antibodies or fusion proteins incorporating two different functional
      proteins opens exciting opportunities for new therapeutic modalities. These
      developments will hopefully offset the impediments to the successful use of RIT.

PMID- 11471489
TI  - Effect of omega-3 fatty acid (docosahexanoic acid) on BRCA1 gene expression and
      growth in MCF-7 cell line.
AB  - Recently, we have demonstrated that omega-6 fatty acid linoleic acid (LA) in
      presence of estradiol (E2) enhances proliferation and anchorage independent
      growth with down regulation of BRCA1 mRNA expression in MCF-7 cell line. Since
      omega-3 fatty acid (docosahexanoic acid, DHA) is known to block the promoting
      effect of omega-6 polyunsaturated fatty acid (LA), we wanted to see whether
      addition of DHA can inhibit the growth of MCF-7 cells which are exposed to LA +
      E2 and any alteration of BRCA1 mRNA expression could be seen in DHA treated
      culture. Experiments on MCF-7 cells with DHA revealed both decrease in
      proliferation and anchorage independency as compared to controls; while no change
      of BRCA1 mRNA expression was observed. Further, when DHA was administered to
      cells along with LA + E2, no change in BRCA1 expression was observed, however, a
      marked decrease in proliferation and soft agar colony formation was evident,
      indicating inhibition of MCF-7 cells following DHA treatment. Flow cytometric
      analysis showed that DHA treated cells either alone or in combination with LA +
      E2 induced marked G1/S and G2/M arrest of the cells, suggesting the inhibitory
      effect of DHA at this phase of cell cycle. However, neither typical DNA ladder
      nor fragmented nuclei or apoptotic bodies were observed, ruling out presence of
      apoptosis following DHA treatment.

PMID- 11471490
TI  - Sentinel lymph node mapping in melanoma with technetium-99m dextran.
AB  - PURPOSE: The aim of this work is to evaluate the capability of Tc99m B Dextran as
      a lymphoscintigraphic agent in the detection of the sentinel node in skin
      lesions. MATERIALS AND METHODS: Forty-one patients with melanomas (39) and Merkel
      cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours
      before surgery. Serial gamma camera images and a handheld gamma probe were used
      to direct sentinel node biopsy. RESULTS: In 39/41 patients, lymph channels and 52
      sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one
      patient, with a dorsal melanoma, no lymph channels or lymph nodes could be
      demonstrated on the images and only minimal radioactivity was found in the
      regional nodes with the probe. Another patient with a facial lesion failed to
      demonstrate lymph channels or nodes. No adverse reactions were observed.
      CONCLUSION: Tc99m-Dextran provided good definition of lymph channels and sentinel
      node localization, without the risks related to the use of potentially hazardous
      labeled materials of biological origin.

PMID- 11471491
TI  - [Enzootic ulcer in the back of the tongue in cattle after ingestion of hay
      containing flower clusters of yellow bristle-grass].
AB  - Chronically recidivating enzootic ulcerations in the tongues of numerous milking
      cows in the Po river plain area in Italy. The animals were permanently kept
      indoors in cubicle houses and fed by hay containing high amounts of ripe yellow
      bristle grass (Setaria glauca (L.) Beauv. [= S. pumila Poiret]). The panicled
      parts of the culms were found to be the cause of the massive injuries.

PMID- 11471492
TI  - [Animal nutrition for veterinarians--recent cases: odor variations in eggs from
      brown hens and also possibly in "noncritical" feed composition].
AB  - Fishy or unpleasant egg taint occurred in a high frequency (10%) in a herd of
      brown layers. The hens were fed a commercial standard diet, that did not contain
      the known critical ingredients as fish meal or rape seed and had an average
      choline concentration. Sensory tests of the drinking water did not reveal any
      abnormalities. In a subsequent feeding trial an oral antibiotic treatment with
      neomycin alone had no positive effects while neomycin and tetracycline reduced
      egg taint significantly until it became almost normal. Microbial activities in
      the GI tract were therefore obviously responsible for the egg taint.

PMID- 11471493
TI  - [Impact of lactic acid fermentation in the large intestine on acute lactic
      acidosis in cattle].
AB  - Microbial and fermentation changes in the ingesta of the large intestine and
      their influence on the pathogenesis of acute lactic acidosis were studied in 4
      cows fitted with permanent cannulas in the ileum and cecum. Feed mixture
      containing 65% of maize was infused into the cecum for several days in amounts of
      2 and 4 kg per day. The daily amount was divided in 8 equal portions and given
      with 3 l of warm physiologic saline solution. During the period of ad libitum
      feeding of hay, the pH values in cecal digesta were 7.4 to 7.6 and the amount of
      total volatile fatty acids 40-60 mmol/kg with high molar percentage (87-90 mol%)
      of acetic acid. As to lactic acid only the L(+) lactic isomer was found in a
      concentration of about 0.4 mmol/kg. Infusion of low amounts of starch induced
      mild lactic acid fermentation in the cecum associated with a pronounced increase
      in the concentration of L(+) and D (-) lactic acid to peak levels of 80 +/- 10
      mmol/kg and 7 +/- 1 mmol/kg, respectively. Lactic acid fermentation ceased within
      2 to 3 days indicating that the gut microflora had adapted to the starch
      infusion. Slight decreases of blood pH and bicarbonates in blood as well as a
      moderate increase of netto acid-base excretion in urine indicated mild changes of
      acid-base balance, but clinically no pathological symptoms were observed. Higher
      amounts of infused starch caused pronounced lactic acid production in the large
      intestine which persisted throughout the experiment. Peak L(+) and D(-) lactic
      acid concentration in cecal digesta reached on the average 137 +/- 16 mmol/kg and
      45 +/- 7 mmol/kg respectively. Significant decreases of blood pH values from 7.41
      +/- 0.02 to 7.18 +/- 0.08 (P < 0.001), actual bicarbonate from 28.2 +/- 3.2 to
      11.0 +/- 2.6 mmol/l (P < 0.001) and base excess from 3.9 +/- 3.6 to -15.2 +/- 3.8
      mmol/l (P < 0.001) were observed. D (-) lactic acid concentration in blood
      increased to 3.2 +/- 0.4 mmol/l, but L(+) lactic acid values remained unchanged
      under 1 mmol/l. Clear clinical symptoms of indigestion and intoxication
      characterized by severe inappetence, ruminal stasis and general weakness were
      also observed. Typical clinical symptoms of disease as well as blood and urine
      changes in acid-base balance indicated that lactic acid fermentation in the large
      intestine contributes considerably to the pathogenesis of acute ruminant lactic
      acidosis.

PMID- 11471494
TI  - Effects of regrouping, feeding and drinking methods on weight gain of weaned
      piglets.
AB  - The effects of alterations in regrouping, feeding and drinking practices were
      examined on a pig farm to improve animal welfare and productivity. Weaned at 35
      days of age, 720 piglets were randomly assigned to 24 groups of 30 piglets in a
      factorial design with three factors. During the next 55 days they were regrouped
      once, twice or not regrouped at all, had nipple drinkers or a water trough and
      had 3, 6 or 10 cm trough length per animal and four meals a day or 3 cm trough
      length per animal and six daily meals. Simple factorial ANOVA revealed that the
      piglets grew very highly significantly (p < 0.001) faster if they were not
      regrouped, drank from water troughs and had sufficient trough length available,
      however, increased feeding frequency partially compensated for shorter trough
      length. Similar analysis of the ranges of body weights within groups showed
      similar, yet less significant effects in the opposite direction, i.e. where pigs
      grew faster there tended to be also less weight difference. It is concluded that
      avoidance of mixing and undisturbed, easy access to food and water is beneficial
      to both the welfare of the pigs as well as their productivity.

PMID- 11471495
TI  - Phospholipid- and fatty acid-composition in the erythrocyte membrane of the one
      humped camel [Camelus dromedarius] and its influence on vesicle properties
      prepared from these lipids.
AB  - The lipid composition of the membrane of erythrocytes from the one-humped camel
      (Camelus dromedarius) concerning the different lipid classes and the fatty acids
      was investigated for the first time. The most frequently occurring lipids are
      sphingomyelin (28.8% of total lipids), phosphatidylcholine and phosphatidylserine
      (each about 12%). The cholesterol/lipid ratio was calculated to be 0.30 (w/w).
      The fatty acids consist of shorter and/or more unsaturated chains, which resulted
      in a more fluid membrane compared to human RBC membranes. Liposomes prepared from
      erythrocyte lipid extracts were used to investigate the membrane properties
      resulting from this special lipid mixture. These vesicles were sufficient stable
      in buffer and significantly more stable than vesicles prepared from human
      erythrocyte lipid extracts in serum at 37 degrees C. Lipoplexes prepared from
      cationic erythrocyte lipid liposomes and a reporter gene showed in vitro an
      improved transfection on two colon carcinoma cells with an enhancement of up to
      400% in beta-galactosidase activity in comparison to Lipofectin.

PMID- 11471496
TI  - Antioxidants and lipid peroxidation levels of blood and cervical mucus in cows in
      relation to pregnancy.
AB  - Levels of vitamins A and E, beta carotene and lipid peroxidation product (TBARS)
      were determined in plasma and cervical mucus of 32 cows. Red blood cell (RBC)
      reduced glutathione (GSH) and RBC glutathione peroxidase (GSH-Px) activity as
      well as vitamin C plasma levels were measured. After taking cervical mucus and
      blood samples the animals were inseminated artificially. Three month later
      pregnant (n = 20) and non pregnant (n = 12) cattle were determined. Correlations
      between investigated parameters and pregnancy rate were performed. In blood
      plasma, a significant correlation was observed between vitamin A and beta
      carotene (P < 0.001) as well as vitamin E (P < 0.05). There was a significant (P
      < 0.001) correlation in TBARS values of plasma and cervical mucus. However, none
      of the investigated parameters showed a significant difference between pregnant
      and non pregnant cows. In conclusion, we did not find any difference and
      correlation between pregnant and nonpregnant animals concerning the investigated
      antioxidants. A positive correlation was observed between lipid peroxidation
      levels of plasma and cervical mucus. Our work provides basic informations about
      antioxidative parameters under physiological conditions. Further studies should
      investigate possible correlation between disturbed fertility and antioxidative
      status of plasma and cervical mucus in clinically healthy cows.

PMID- 11471497
TI  - [Bounderies of the authorization to market and the therapeutic impass].

PMID- 11471498
TI  - [Evaluation of implantable sites in medical oncology in Tunisia. Prospective
      study of 205 cases].
AB  - OBJECTIVE: To evaluate the insertion and use of implantable central venous
      accesses in medical oncology at the Institute Salah Azaiz. METHODS: From January
      1992 to June 2000, 205 patients including 179 adults (118F/61M) and 26 children
      aged 7 months to 72 years (mean 37 years) required the insertion of an
      implantable port (IP). Tumoral pathology was dominated by metastatic breast
      carcinoma (93/179), digestive cancer (42/179) and paediatric cancer (26 cases).
      RESULTS: Excluding 3 initial failures, we inserted 205 IP for 202 patients. The
      supraclavicular anatomic way (Yoffa) was used in 156/205 cases and the
      subclavicular (Aubaniac) for the resting 32 cases with a jugular conversion in 17
      cases. Initial complications were represented by 6 arterial puncture (2.9%), 3
      pneumothorax (1.5%) and 1 catheter migration in the right pulmonary artery.
      Median life duration of the material was 210 days (3 to 1460 days) for adults and
      185 days (3 to 1460 ays) for children. Mean life duration for the 205 IP was 240
      days +/- 239 (3 to 1460 days) with a total of 49,200 IP-days. We explanted 17 IP
      for infection (8 cases), cutaneous ulceration (8 cases) and actinomycin
      extravasation (1 case). We observed 6 cases (2.9%) of subclavian and jugular
      thrombosis treated by anticoagulants and conservation management of the port.
      Presently, 58 patients are alive with IP in place. CONCLUSION: Implantable ports
      represent a useful option in medical oncology for patients treated with prolonged
      chemotherapy and adjuvant treatments such as antibiotics, transfusion. This
      method allows a good comfort for the patients and also the treating team but
      requires a prealable training for the nursing team.

PMID- 11471499
TI  - [Hemophagocytosis during multiple organ failure: M-CSF overproduction or viral
      reactivation?].
AB  - OBJECTIVE: This study was aimed to assess the potential role of M-CSF and viral
      reactivation in the genesis of haemophagocytosis during the multiple organ
      failure (MOF) syndrome. METHODS: Twenty-five patients (mean age: 60 +/- 16 years;
      Apache II: 23 +/- 5) sustaining MOF with an unexplained thrombocytopenia were
      studied. In each patient, a bone marrow aspirate, serum M-CSF concentration, and
      a virological examination (Herpes viruses) were obtained on admission. In
      addition, 20 patients (mean age: 57 +/- 15 years; Apache II: 24 +/- 7) with at
      least two organ failures but no thrombocytopenia constituted the control group.
      Circulating M-CSF levels and the frequency of virus reactivation were compared
      between groups. RESULTS: Haemophagocytosis was diagnosed in 11/25 patients (44%).
      No viral reactivation was found. Serum M-CSF concentrations were higher in the
      presence of haemophagocytosis (699 +/- 242 vs 438 +/- 157 IU.mL-1; p < 0.05).
      Ferritin levels were also increased in the presence of a macrophage activation
      (3,258 +/- 2,807 vs. 520 +/- 280 mg.L-1; p < 0.0001). In contrast, both
      circulating M-CSF and ferritin levels were similar between thrombocytopenic
      patients with no hemophagocytosis and controls. CONCLUSIONS: This study confirmed
      the high incidence of haemophagocytosis in critically ill patients sustaining
      MOF. In this setting, circulating M-CSF levels were markedly elevated, whereas no
      Herpes viruses reactivation was found.

PMID- 11471500
TI  - [Catheter-related infection in intensive care. Physiopathology, diagnosis,
      treatment and prevention].
AB  - PURPOSE: To review the mechanisms, diagnosis, treatment and prophylaxis of
      catheter-related sepsis in intensive care unit patients. DATA SOURCES: A Medline
      research of the English- or French-language reports published between 1966 and
      2000 and a manual research of references of relevant papers. STUDY SELECTION:
      Experimental, clinical and basic research studies related to catheter-related
      sepsis. DATA EXTRACTION: Data in selected articles were reviewed, and relevant
      clinical information was extracted. DATA SYNTHESIS: Infection remains the major
      complication related to catheter insertion. No bacteriological exam or systematic
      catheter change is required in the absence of infection suspicion. In the
      intensive care unit, and without septic shock, the surveillance of skin cultures
      at the catheter insertion site or the time to positivity of hub-blood versus
      peripheral-blood culture determination may reduce the number of unnecessary
      removed catheters. Catheter change over a guidewire is not recommended because of
      the risk of dissemination of infection. When the catheter is removed, a
      quantitative culture is warranted. The treatment of catheter-related sepsis is
      based on catheter removal. The use of antibiotics is limited to some organisms or
      when the infection is complicated. The persistence of fever and positive blood
      cultures 72 h after catheter removal require to look for dissemination of
      infection or septic thrombophlebitis, especially if S. aureus or Candida are
      incriminated. The treatment of infection without catheter removal is not
      recommended in the intensive care unit because of a high risk of treatment
      failure. Compliance with catheter care guidelines and continuing quality
      improvement programs are the two major procedures in reducing catheter infection.
      CONCLUSIONS: Improved understanding of the pathophysiology of catheter-related
      sepsis has led to improved prevention. Compliance with catheter care guidelines
      and continuing quality improvement programs are majors procedures to reduce the
      risk of catheter infection.

PMID- 11471501
TI  - [French and foreign recommendations for the practice of anesthesia-intensive
      care].
AB  - This article reviews the development of STANDARDS, Recommendations and Guidelines
      for practice in anaesthesiology in France and other countries. The French society
      for anaesthesia and intensive care (Sfar) has published, since 1989, 11 basic
      STANDARDS: 1) Recommendations for the monitoring of patients during anaesthesia
      (June 1989, amended on January 1994) [APSF Newsletter, Summer 1990, page 22]; 2)
      Recommendations for postanaesthesia monitoring and care (September 1990); 3)
      Recommendations for preanaesthesia care (September 1991); 4) Recommendations for
      anaesthetic apparatus and checking before use (January 1994); 5) Recommendations
      for the equipment of anaesthesia working places (January 1995); 6)
      Recommendations for the tasks of the nurse anaesthetist (January 1995); 7)
      Recommendations for hygiene standards in anaesthesia practice (December 1997); 8)
      Recommendations for outpatient anaesthesia (September 1990); 9) Recommendations
      for the practice of obstetrical analgesia (September 1992); 10) Recommendations
      for interhospital physician-accompanied transfers (December 1992); 11)
      Recommendations for intrahospital physician-accompanied transfers (February
      1994). Additionally the Sfar produced or coproduced 9 Experts' conferences, 15
      Consensus conferences and 5 Guidelines for clinical practice.

PMID- 11471502
TI  - [Postoperative otorrhagia: an unknown complication of Trendelenburg position
      during laparoscopic surgery?].
AB  - Two patients have presented postoperative otorrhagia following gynaecologic
      laparoscopic procedures. This occurred after uneventful anaesthesia and recovery
      for surgery performed in forced Trendelenburg position (35 degrees with
      horizontal position). Different responsible mechanisms are discussed including
      haemodynamic changes induced by both the Trendelenburg position and the
      pneumoperitoneum. Particularities of external ear blood supply directly submitted
      to arterial and venous pressure changes, may also have contributed to the
      appearance of otorrhagia.

PMID- 11471503
TI  - [Liver transplantation in a patient with hemophilia A and end stage liver
      failure].
AB  - We report the case of a 50 year-old man factor VIII deficient haemophiliac and
      hepatitis C cirrhosis. The patient underwent orthotopic liver transplantation
      because of episodes of variceal bleeding and encephalopathy. He received factor
      VIII replacement therapy perioperatively. Factor VIII returned to normal within
      24 hours postoperatively and factor VIII replacement was stopped. Liver
      transplantation can be considered as definitive therapy for haemophilia.

PMID- 11471504
TI  - [Pulmonary embolism in sclerotherapy for a venous malformation in a child under
      general anesthesia].
AB  - We report a case of pulmonary embolism associated with percutaneous sclerotherapy
      (absolute ethanol: 0.5 mL.kg-1) of a venous angioma, performed under general
      anaesthesia in a 13 year-old child. The diagnosis of pulmonary embolism,
      suspected on the clinical setting and symptoms, was supported by the pulmonary
      scintigraphy obtained 4 hours later, showing 3 minimal pulmonary defects. The
      outcome was rapidly favourable without sequelae under heparin administration and
      the pulmonary scintigraphy, performed on day 7, was normal. The role of absolute
      ethanol, for explaining the apparent contrast between the severity of the
      symptoms and the minimal obstruction noted on pulmonary scintigraphy is
      discussed. Also discussed are the prophylactic and curative therapeutic issues of
      this severe complication.

PMID- 11471505
TI  - [Acute respiratory distress syndrome after prolonged hyperbaric oxygen therapy: a
      case of pulmonary oxygen toxicity?].
AB  - A 42-year-old patient was admitted to our ICU for severe decompression illness
      with tetraplegia. He presented an acute respiratory distress syndrome (ARDS),
      following a very long hyperbaric oxygen therapy (using a US. Navy Treatment Table
      7). The ARDS resulted in pulmonary fibrosis, and the patient died despite maximal
      support in ICU. The risk of pulmonary toxicity of oxygen must be considered when
      using a prolonged recompression treatment table.

PMID- 11471506
TI  - [Intracranial subdural hematoma after obstetric dural puncture].
AB  - The authors report a case of subdural haematoma (HSD), which occurred following
      epidural analgesia for labour, complicated by post dural puncture headache
      (PDPH). A 26-year-old woman displayed a typical PDPH following epidural
      anaesthesia. On the sixth day, she was given a blood patch (BP), which was
      partially efficacious. Because of worsening of the headache, of disappearance of
      the postural characteristics, and of vomiting without focal neurological signs on
      the 9th day, a CT-scan was done. The CT-scan showed a small hemispheric subdural
      haematoma. The recovery was complete with only medical treatment. HSD is a rare
      serious complication of dural puncture. When the characteristics of PDPH change,
      HSD should be evoked even without focal neurological signs. An early diagnosis
      and the small size of the haematoma may allow HSD to be treated medically and
      avoid surgical evacuation.

PMID- 11471507
TI  - [Hemodynamic instability and paraplegia after thoracotomy for excision of a
      cardiac pheochromocytoma].
AB  - We report the occurrence of a sustained hypotension (vasoplegia) following
      thoracic phaeochromocytoma surgery. Diagnosis of spinal cord injury was done by
      magnetic nuclear resonance (MNR) showing surgical "Horsley wax" inside the
      vertebral canal and ischaemic signal inside the anterior part of the spine cord.
      Removal of "Horsley wax" dramatically improved arterial blood pressure but did
      not correct all neurologic disorders. Haemodynamic disorders related to spinal
      cord injury are rare after thoracotomy, and may have been enhanced by the
      haemodynamic instability typically associated with phaeochromocytoma surgery.
      Early diagnosis has to be done by MNR.

PMID- 11471508
TI  - [Recombinant hirudin in neurosurgery].
AB  - We report the case of a 70-year-old woman with paraplegia resulting from spinal
      cord compression secondary to an epidural haematoma. Because of an arrhythmia, a
      mitral valve replacement and the high risk of venous thrombosis, an anticoagulant
      treatment was introduced postoperatively. The patient having previously developed
      an type II heparin-induced thrombocytopaenia, a treatment by lepirudine was
      established successfully.

PMID- 11471509
TI  - [Unusual complication of extubation].

PMID- 11471510
TI  - [Perforation by a tracheal probe: an unusual complication of central venous
      catheterization].

PMID- 11471511
TI  - [Massive rhabdomyolysis in capillary hyperpermeability].

PMID- 11471512
TI  - [Does research in anesthesia-intensive care improve our practice?].

PMID- 11471513
TI  - [Does progress in intensive care reduce mortality?].

PMID- 11471514
TI  - [The role of the anesthesiologist-intensive care physician in the surgical unit.
      Round table at the 42nd national congress of the Societe francaises d'anesthesie
      et de reanimation ].

PMID- 11471515
TI  - Etanercept and infliximab for rheumatoid arthritis.
AB  - Etanercept (Enbrel--Wyeth) and infliximab (Remicade--Schering Plough) belong to a
      new class of drugs that block the effects of tumour necrosis factor-alpha (TNF
      alpha), a mediator of inflammation. Both are licensed for the treatment of
      patients with active rheumatoid arthritis who have responded inadequately to
      disease-modifying antirheumatic drugs (DMARDs). Here, we consider whether
      etanercept and infliximab offer advantages.

PMID- 11471516
TI  - Stimulant drugs for severe hyperactivity in childhood.
AB  - It is estimated that 0.5-1.4% of school-aged children in England and Wales have
      severe hyperactivity, a syndrome characterised by impulsiveness, inattention and
      overactivity. In the UK, two CNS stimulants, methylphenidate and dexamfetamine
      (dexamphetamine), are licensed for treating childhood hyperactivity where non
      drug measures along have proved insufficient. In 1995, we concluded that
      behavioural and educational approaches should be first-choice steps in most
      children with hyperactivity, with stimulant drugs being reserved for children in
      whom the disorder is severe or who are resistant to non-drug treatments. Here, we
      reassess the place of stimulant drugs in the management of severe hyperactivity
      in children.

PMID- 11471517
TI  - Linezolid for gram-positive infections.
AB  - Linezolid (Zyvox--Pharmacia)--the first oxazolidinone antibacterial--is marketed
      in the UK for treating hospital- and community-acquired pneumonia, skin and soft
      tissue infections. The manufacturer claims that switching from i.v. to oral
      administration of linezolid needs no dose adjustment and "will lead to early
      patient discharge and reduced hospital length of stay" for patients needing
      treatment for infections caused by Gram-positive bacteria, including methicillin
      resistant Staphylococcus aureus (MRSA). Here, we assess the place of linezolid.

PMID- 11471518
TI  - Ventricular myosin light chain-2 gene expression in developing heart of chicken
      embryos.
AB  - Recent gene knock-out studies in mice have suggested that ventricular myosin
      light chain-2 (vMLC2) has a role in the regulation of cardiogenic development and
      that perturbation in expression of vMLC2 is linked to the onset of dilated
      cardiomyopathy. In an attempt to develop an avian model for such studies, we
      examined the expression pattern of vMLC2 in chicken embryos at various stages and
      analyzed the effect of antisense oligonucleotide-mediated interference of vMLC2
      function in cultures of whole embryos. Our results showed vMLC2 to be a specific
      marker for ventricular chamber throughout chicken embryonic development and
      antisense vMLC2 treatment of primitive streak stage (stage 4) embryos to produce
      pronounced dilation of heart tube with severe deficiency in formation of striated
      myofibrils. Further studies with antisense mRNA techniques of whole embryo
      cultures should, therefore, be useful to evaluate the role of vMLC2 and other
      putative regulatory factors in cardiac myofibrillogenesis.

PMID- 11471519
TI  - A segment and epithelium specific messenger ribonucleic acid fragment up
      regulated by estradiol in the rat oviduct.
AB  - Estradiol accelerates oviductal embryo transport in the rat through changes of
      genomic expression in oviductal cells. However, the genes involved are unknown.
      We used a differential display by reverse transcription-polymerase chain reaction
      to detect estradiol (E2)-dependent genes in the rat oviduct. Rats on day 2 of
      pregnancy were untreated or treated with 10 micrograms of E2 and the oviducts
      were extracted at 30, 180 and 360 min later and used to isolate RNA. Products of
      reverse transcriptase-PCR, made with pairs of arbitrary and oligo-deoxythymidine
      primers, were separated on denaturing polyacrylamide gels and candidate bands
      were excised and reamplified. Truly positive cDNA fragments determined by a
      single strand conformation polymorphism assay were cloned and sequenced. A
      ribonuclease protection assay confirmed that clone 25 is up-regulated by E2 in
      the oviduct at 30, 180 and 360 min. This clone exhibited no homology with known
      genes and in situ hybridization showed it is only expressed in the epithelial
      cells of the isthmic segment. Clone 25 is likely to represent a new gene, which
      is up-regulated by E2 in the epithelium of the isthmic segment of the rat
      oviduct. Its time frame of response is compatible with a mediator of the effect
      of E2 on oviductal embryo transport.

PMID- 11471520
TI  - Genetic polymorphism in eight Chilean strains of the carotenogenic microalga
      Dunaliella salina Teodoresco (Chlorophyta).
AB  - Eight Chilean strains of Dunaliella salina obtained within a restricted
      geographic range, but exhibiting a high variability in their morphology, rate of
      growth and carotenogenic capacity, were analyzed by Random Amplified Polymorphic
      DNA (RAPD-PCR) Twenty of the 50 random primers (D, P, OPA and OPD series) that
      were tested amplified reproducible bands and were useful for comparative analysis
      of the strains. Of 107 polymorphic genetic markers, 49 were strain-specific. A
      great genetic variability was found among the strains in spite of their
      geographic proximity. In addition, phenetic analysis of the data showed close
      agreement between the morphophysiological attributes and the genetic diversity of
      the strains.

PMID- 11471521
TI  - Distribution of delta sleep-inducing peptide in the newborn and infant human
      hypothalamus: an immunohistochemical study.
AB  - The distribution of delta sleep-inducing peptide immunoreactive cell bodies,
      fibers, and terminal-like structures was investigated in the normal human
      hypothalamus during the first postnatal year, using immunohistofluorescence and
      peroxidase anti-peroxidase techniques. Immunolabeled perikarya were relatively
      few and were mostly scattered through the anterior (preoptic) and mediobasal
      regions (infundibular nucleus) of the hypothalamus. DSIP-immunoreactive fibers
      and terminal-like fibers were observed throughout the entire rostrocaudal extent
      of the hypothalamus. They exhibit high densities in the preoptic region, the
      organum vasculosum of lamina terminalis, infundibular nucleus and median
      eminence. Moderate to low densities of DSIP-immunoreactive fibers were observed
      in the other hypothalamic structures, located in the anterior and mediobasal
      regions of hypothalamus, such as periventricular, paraventricular,
      suprachiasmatic, ventromedial, dorsomedial and parafornical nuclei. In the
      present study, the analysis of the immunohistochemical pattern of DSIP
      immunoreactive neuronal elements in the human infant hypothalamus during the
      first postnatal year provided evidence of the presence of several differences. We
      have found qualitative age-related changes in the density of DSIP
      immunoreactivity in several hypothalamic structures such as the anterior region
      and the median eminence.

PMID- 11471522
TI  - Participation of the phosphoinositide metabolism in the hypersensitive response
      of Citrus limon against Alternaria alternata.
AB  - Lemon seedlings inoculated with Alternaria alternata develop a hypersensitive
      response (HR) that includes the induction of Phenylalanine ammonia-lyase (PAL, E.
      C. 4.3.1.5) and the synthesis of scoparone. The signal transduction pathway
      involved in the development of this response is unknown. We used several
      inhibitors of the Phosphoinositide (PI) animal system to study a possible role of
      Inositol-1,4,5-triphosphate (IP3) in the transduction of the fungal conidia
      signal in Citrus limon. The HR was only partially inhibited by EGTA, suggesting
      that not only external but internal calcium as well are necessary for a complete
      development of the HR. In this plant system, Alternaria alternata induced an
      early accumulation of the second messenger IP3. When lemon seedlings were watered
      long term with LiCl, an inhibitor of the phosphoinositide cycle, the IP3
      production was reduced, and the LiCl-watered plants could neither induce PAL nor
      synthesize scoparone in response to fungal conidia. Furthermore, neomycin, a
      Phospholipase C (PLC, E. C. 3.1.4.3) inhibitor, also inhibited PAL induction and
      scoparone synthesis in response to A. alternata. These results suggest that IP3
      could be involved in the signal transduction pathway for the development of the
      HR of Citrus limon against A. alternata.

PMID- 11471523
TI  - In situ hybridization of somatolactin transcripts in the pituitary glands from
      acclimatized carp (Cyprinus carpio).
AB  - We isolated and cloned a carp somatolactin SL DNA fragment, of which 78% of the
      nucleotides were identical to the corresponding salmon SL sequence. The results
      obtained upon Northern blot hybridization of carp pituitary RNA allowed the
      identification of two transcripts as described for other fish. When the content
      of SL transcripts in pituitary sections from summer- and winter-acclimatized carp
      was quantified by in situ hybridization assays, we found no significant
      differences between the two seasons. In salmonids, plasma SL reaches higher
      levels in summer than in winter in synchrony with the water temperature cycle; in
      the eurythermal carp, however, the complex adaptive responses imposed by seasonal
      environmental changes do not seem to include the regulation of the somatolactin
      detected with the probe used at the transcriptional level in pituitary glands.

PMID- 11471524
TI  - [Fortification of the biological sciences in Chile in the postgenomic era].

PMID- 11471525
TI  - [Science in Chile and the Milenio Program].

PMID- 11471526
TI  - Using patient decision aids to promote evidence-based decision making.

PMID- 11471527
TI  - Treatment of pulmonary disease following cervical spinal cord injury.

PMID- 11471529
TI  - Patient safety alert. Risk management eliminated in wide-ranging program.

PMID- 11471528
TI  - Giardiasis-associated arthralgia in children.
AB  - BACKGROUND: Giardiasis is the most common intestinal parasitosis in Mexico. Usual
      symptoms of the acute infection are diarrhea, abdominal pain, nausea, and weight
      loss. Children are more frequently affected than adults. Various extra-intestinal
      manifestations have been reported, among which are arthritis and arthralgia.
      METHODS: A series of 10 children with arthralgia and cysts of Giardia lamblia in
      feces seen during 13 years of private practice were presented. Ages ranged
      between 5 and 11 years, and 70% of the children are males. RESULTS: The joints
      involved in all cases were the knee and the ankle. No joint flogosis or changes
      in local temperature were observed. Other associated symptoms were abdominal pain
      (100%), abdominal distension (70%), flatulence (50%), less consistent stools
      (50%), anemia (30%), and increased erythrocyte sedimentation rate (60%). C
      reactive protein and rheumatoid factor were negative in all cases. Arthralgia
      disappeared after treatment with metronidazole when coproparasitoscopic analyses
      were negative. CONCLUSIONS: Arthralgia associated with giardiasis in children is
      a rare entity, relatively benign, and leaves no sequelae.

PMID- 11471530
TI  - Patient safety alert. Patient safety tool focuses on best practices.

PMID- 11471531
TI  - Patient safety alert. ER demand still rising, endangering patients.

PMID- 11471532
TI  - Bibliography. Current world literature. Stones.

PMID- 11471533
TI  - Bibliography. Current world literature. Voiding dysfunction and female urology.

PMID- 11471534
TI  - Effects of direct sympathetic and vagus nerve stimulation on the physiology of
      the whole heart--a novel model of isolated Langendorff perfused rabbit heart with
      intact dual autonomic innervation.
AB  - A novel isolated Langendorff perfused rabbit heart preparation with intact dual
      autonomic innervation is described. This preparation allows the study of the
      effects of direct sympathetic and vagus nerve stimulation on the physiology of
      the whole heart. These hearts (n = 10) had baseline heart rates of 146 +/- 2
      beats x min(-1) which could be increased to 240 +/- 11 beats x min(-1) by
      sympathetic stimulation (15 Hz) and decreased to 74 +/- 11 beats x min(-1) by
      stimulation of the vagus nerve (right vagus, 7 Hz). This model has the advantage
      of isolated preparations, with the absence of influence from circulating hormones
      and haemodynamic reflexes, and also that of in vivo preparations where direct
      nerve stimulation is possible without the need to use pharmacological agents.
      Data are presented characterising the preparation with respect to the effects of
      autonomic nerve stimulation on intrinsic heart rate and atrioventricular
      conduction at different stimulation frequencies. We show that stimulation of the
      right and left vagus nerve have differential effects on heart rate and
      atrioventricular conduction.

PMID- 11471535
TI  - Metabolism changes in single human fibres during brief maximal exercise.
AB  - Changes in high-energy phosphate levels in single human skeletal muscle fibres
      after 10 s of maximal (all-out) dynamic exercise were investigated. Muscle
      biopsies from vastus lateralis of two volunteers were collected at rest and
      immediately post exercise. Single muscle fibres were dissected from dry muscle
      and were assigned into one of four groups according to their myosin heavy chain
      (MyHC) isoform content: that is type I, IIA, IIAx and IIXa (the latter two groups
      containing either less or more than 50% IIX MyHC). Fragments of characterised
      fibres were analysed by HPLC for ATP, inosine-monophosphate (IMP),
      phosphocreatine (PCr) and creatine levels. After 10 s of exercise, PCr content
      ([PCr]) declined by approximately 46, 53, 62 and 59 % in type I, IIA, IIAx and
      IIXa fibres, respectively (P < 0.01 from rest). [ATP] declined only in type II
      fibres, especially in IIAx and IIXa fibres in which [IMP] reached mean values of
      16 +/- 1 and 18 +/- 4 mmol (kg dry mass)(-1), respectively. While [PCr] was
      reduced in all fibre types during the brief maximal dynamic exercise, it was
      apparent that type II fibres expressing the IIX myosin heavy chain isoform were
      under a greatest metabolic stress as indicated by the reductions in [ATP].

PMID- 11471536
TI  - Re; Witzke JD et al. Stapled versus hand sewn anastomes in patients with small
      bowel injury: a changing perspective. J Trauma. 2000;49:660--665.

PMID- 11471537
TI  - The aetiology of Himalayan endemic goitre. 1961.

PMID- 11471538
TI  - Prevention of endemic goitre with iodized salt. 1973.

PMID- 11471539
TI  - Cytoplasmic expression of ribozyme in zebrafish using a T7 autogene system.
AB  - A cytoplasmic ribozyme expression system, based on codelivery of a ribozyme
      vector, a T7 autogene vector, and T7 RNA polymerase (RNAP), has been developed
      and used to generate a specific phenotype in zebrafish by targeting a no tail
      (ntl) mRNA. The expression of the no tail ribozyme sequence is under the control
      of a tandem of two promoters: The T7 promoter and an adenoviral va 1 (pol III)
      promoter. The coinjection of the ribozyme vector pT7vaRz, the T7 autogene vector
      pT7T7, and the T7 RNAP resulted in rapid synthesis of the ribozyme against the
      ntl mRNA in the cytoplasm of the injected zebrafish embryos, generating no tail
      phenotypes in up to 10-20% of the injected embryos. The phenotypic change rates
      have been found to be related to the concentrations of the plasmid vectors and T7
      RNAP injected and to the ratios of the three injected components. This
      cytoplasmic ribozyme expression system may be useful for efficiently targeting
      other mRNA and for various biomedical applications. These potential applications
      may include rapid identification of biological functions of novel genes from
      zebrafish and humans based on partial gene sequence information and gene therapy
      of genetic and acquired diseases.

PMID- 11471540
TI  - In situ NMR systems.
AB  - In situ NMR is becoming an established technology for applications in
      bioprocessing and metabolic engineering. The in situ NMR biosensor acts as a
      noninvasive pH, ion, and concentration meter, with 31P and 13C as the two main
      isotopes of study. A substantial data base now exists for phosphorus and carbon
      spectra of bacteria and yeast. In situ NMR can provide many of the state
      variables needed for modeling glycolytic pathway function. NMR micro-reactor
      technology has improved significantly in the last decade. Several designs for
      immobilized cell reactors have been tested, and in particular, considerable gains
      have been made in the feasibility of studying aerobic, chemostat cultures with in
      situ NMR. Acquisition of 31P spectra from cell suspensions of 3-5% v/v under
      controlled conditions can be made in 3-7 minute time resolution in several
      systems.

PMID- 11471541
TI  - NMR and microorganisms.
AB  - This article is an introduction to the use of NMR for the investigation of
      microbial physiology and metabolism. NMR parameters which determine the
      sensitivity and resolving power of the method are reviewed. A broad survey of
      current applications follows. Qualitative uses are described first; they include
      compound identification and localisation. Quantitative aspects, such as pH,
      concentration and flux measurements are then examined, as well as the
      corresponding experimental constraints. The review ends with suggestions of
      possible future developments in instrument capabilities aimed at improving
      sensitivity: higher fields, spectroscopic and imaging microprobes.

PMID- 11471542
TI  - Biological rhythms: an analysis of the archives.

PMID- 11471543
TI  - Private researchers raise ante by creating blastocytes to grow stem cells in
      culture.

PMID- 11471544
TI  - The model of the clinical practice of emergency medicine.

PMID- 11471545
TI  - Regulation of laminin 1-induced pancreatic beta-cell differentiation by alpha6
      integrin and alpha-dystroglycan.
AB  - BACKGROUND: The ability to manipulate the development of pancreatic insulin
      producing beta cells has implications for the treatment of type 1 diabetes.
      Previously, we found that laminin-1, a basement membrane trimeric glycoprotein,
      promotes beta-cell differentiation. We have investigated the mechanism of this
      effect, using agents that block the receptors for laminin-1, alpha6 integrin, and
      alpha-dystroglycan (alpha-DG). MATERIALS AND METHODS: Dissociated cells from 13.5
      day postcoitum (dpc) fetal mouse pancreas were cultured for 4 days with laminin
      1, with and without monoclonal antibodies and other agents known to block
      integrins or alpha-DG. Fetuses fixed in Bouin's solution or fetal pancreas cells
      fixed in 4% paraformaldehyde were processed for routine histology and for
      immunohistology to detect hormone expression and bromodeoxyuridine (BrdU) uptake.
      RESULTS: Blocking the binding of laminin-1 to alpha6 integrin with a monoclonal
      antibody, GoH3, abolished cell proliferation (BrdU uptake) and doubled the number
      of beta cells. Inhibition of molecules involved in alpha6 integrin signaling
      (phosphotidylinositol 3-kinase, F-actin, or mitogen-activated protein kinase) had
      a similar effect. Nevertheless, beta cells appeared to develop normally in alpha6
      integrin-deficient fetuses. Blocking the binding of laminin-1 to alpha-DG with a
      monoclonal antibody, IIH6, dramatically decreased the number of beta cells.
      Heparin, also known to inhibit laminin-1 binding to alpha-DG, had a similar
      effect. In the presence of heparin, the increase in beta cells in response to
      blocking alpha integrin with GoH3 was abolished. CONCLUSIONS: These findings
      reveal an interplay between alpha6 integrin and alpha-DG to regulate laminin-1
      induced beta-cell development. Laminin-I had a dominant effect via alpha-DG to
      promote cell survival and beta-cell differentiation, which was modestly inhibited
      by alpha6 signaling.

PMID- 11471546
TI  - Functional characterization of three mutations of the endothelin B receptor gene
      in patients with Hirschsprung's disease: evidence for selective loss of Gi
      coupling.
AB  - BACKGROUND: Hirschsprung's disease (HSCR) is one the most common congenital
      intestinal disease. It leads to aganglionic megacolon in the early childhood.
      Several susceptibility genes have been identified : RET protooncogene and its
      ligand, glial cell derived neutrophic factor (GDNF), Sox 10, Endothelin-3 (EDN3)
      and its receptor B (EDNRB). EDNRB mutations are found in 5% of familial or
      sporadic HSCR. Only few EDNRB mutations found in HSCR have been explored and some
      of them seem to be non fonctional variants. MATERIALS AND METHODS: The properties
      of three mutant human endothelin B receptor (hETB) (G57S, R319W and P383L) in
      isolated HSCR were analyzed. Stable recombinant cells expressing the three
      mutants and the wild-type (WT) were established. The hETB receptors were
      characterized for 125I ET-1 binding, ET-1 induced signaling: calcium transient,
      AP-1 transcriptional factor activation and cAMP accumulation. RESULTS:
      Immunofluorescence experiments showed normal cellular distributions of the mutant
      G57S, R319W and WT hETB receptors. In contrast, the P383L hETB mutant receptor
      was concentrated near the nucleus and essentially no ET-1 binding was detected.
      The two other mutants (G57S and R319W) bound ET-1 normally, induced calcium
      transients and activated the AP-1 pathway in the same way as wild type, but did
      not inhibit adenylate cyclase. The G57S hETB mutant even stimulated cAMP
      accumulation which was blocked by pertussis toxin. CONCLUSION: The absence of the
      P383L mutant receptor from the membrane clearly indicates that this mutation
      could be involved in HSCR. The G57S and R319W mutant receptors, despite their
      normal coupling to Gaq, have a defect in the Galphai signaling pathway and the
      G57S mutation couples to Galphas. These observations allow us to hypothesize that
      cAMP signaling might be involved in the differenciation of neural cells in the
      bowel.

PMID- 11471547
TI  - Alpha1 Na,K-ATPase and Na,K,2Cl-cotransporte/D3mit3 loci interact to increase
      susceptibility to salt-sensitive hypertension in Dahl S(HSD) rats.
AB  - BACKGROUND: Essential (multigenic) hypertension is a complex multifactorial
      disease whose genetic etiology has not been unraveled on a major locus-effect
      investigative paradigm. As with other complex genetic diseases, applying an
      interacting loci paradigm could be critical in the elucidation of genetic
      determinants. Having defined the alpha1 Na,K-ATPase (alpha1NK) as a hypertension
      susceptibility gene in Dahl salt-sensitive (Dahl S) rats, we determined whether
      alphaINK interacts with another renal epithelial Na transporter to increase
      susceptibility to salt-sensitive hypertension. We focused on alpha1NK and
      Na,K,2Cl-cotransporter (NKC) as an a priori candidate interacting gene pair
      because they comprise a functionally linked Na transport system in renal thick
      ascending limb of Henle (TALH) epithelial cells and exhibit altered function in
      prehypertensive Dahl S rats in contrast to Dahl salt-resistant normotensive (Dahl
      R) rats. MATERIAL AND METHOD: Cosegregation analysis of alphaNK and NKC loci was
      done in a (Dahl S x Dahl R) F2 cohort characterized for blood pressure by
      radiotelemetry using the D2mghII microsatellite marker in the alpha1NK gene and
      the D3mit3 microsatellite marker close to the NKC gene (NKC/D3mit3 locus). Single
      locus and digenic analyses were performed to establish the individual and
      interactive genetic contribution to salt-sensitive hypertension. Molecular
      analysis was then done to support the NKC gene as the likely candidate gene
      interacting with alpha1NK in Dahl salt-sensitive hypertension pathogenesis.
      RESULTS: Compared with respective single locus analysis, digenic analysis of 96
      F2 (Dahl S x Dahl R) hybrid male rats revealed cosegregation of alpha1NK and
      NKC/D3mit3 loci as interacting pair with salt-sensitive hypertension with
      markedly increased significance for systolic (one-way ANOVA p = 10(-6)),
      diastolic (p = 10(-5)), and mean arterial (p = 10(-6)) blood pressures.
      Concordantly, two-way ANOVA detected interaction between alpha1NK and NKC loci in
      determining the levels of systolic (p = 0.004), diastolic (p = 0.008), and mean
      arterial (p = 0.006) pressures. To unravel potential NKC molecular dysfunction(s)
      involved in hypertension pathogenesis, we investigated putative differences
      between Dahl S and Dahl R rats in nucleotide sequence and isoform gene expression
      of the renal-specific Na,K,2Cl-cotransporter. Molecular analysis revealed an
      inversion of alternatively spliced NKC-isoform ratios (4B:4A:4F) between Dahl S
      and Dahl R prehypertensive kidneys supported by four mutations in intron-3
      immediately upstream to alternatively spliced exons 4B, 4A, and 4F. No nucleotide
      changes were detected within the aminoacid encoding exons of NKC. CONCLUSIONS:
      Altogether, these current data and previous characterization of the role of the
      Q276L alpha1NK molecular variant in Dahl S hypertension provide cumulative
      compelling evidence that alpha1NK and NKC/D3mit3 loci interact to increase
      susceptibility to hypertension in Dahl S rats and that NKC is the likely
      candidate gene that interacts with alpha 1NK. More importantly, the data
      substantiate gene interaction as an operative mechanism in multigenic
      hypertension.

PMID- 11471548
TI  - Role of transcription factor Nrf2 in the induction of hepatic phase 2 and
      antioxidative enzymes in vivo by the cancer chemoprotective agent, 3H-1, 2
      dimethiole-3-thione.
AB  - BACKGROUND: The induction of phase 2 enzymes by dithiolethiones such as oltipraz
      is an effective means for achieving protection against environmental carcinogens
      in animals and humans. Transcriptional control of the expression of at least some
      of these protective enzymes is mediated through the antioxidant response element
      (ARE) found in the upstream regulatory region of many phase 2 genes. The
      transcription factor Nrf2, which binds to the ARE, appears to be essential for
      the induction of proto-typical phase 2 enzymes such as glutathione S-transferase
      (GST) Ya, Yp, and NAD(P)H: quinone reductase (NQO1) in vivo. MATERIALS AND
      METHODS: In the present study, 3H-1,2-dithiole-3-thione (D3T) was used as a
      potent model inducer whose effects on gene expression and chemopreventive
      efficacy have been extensively characterized in the rat. Over a dozen putative
      D3T-inducible genes were examined in wild-type and nrf2-disrupted mice by
      Northern blot hybridization and reverse transcriptase-polymerase chain reaction
      (RT-PCR) analysis to elucidate whether loss of Nrf2 function also affects the
      induction of a broader representation of phase 2 and antioxidative enzymes. The
      effects of D3T on hepatic Nrf2 expression and localization were also examined in
      vivo by Northern blot hybridization, electromobility shift assay, and Western
      blot analysis. RESULTS: Specific activities of hepatic GST and NQO1 were
      increased by D3T in wild-type mice and were largely blunted in the nrf2-deficient
      mice. However, changes in levels of RNA transcripts following D3T treatment of
      nrf2-disrupted mice were multidirectional, dependent upon the particular gene
      examined. Although elevation of mRNAs for GST Ya, NQO1, microsomal epoxide
      hydrolase and gamma-glutamylcysteine synthetase regulatory chain were blocked in
      the mutant mice, elevation of GST Yp mRNA was largely unimpeded. Increases in
      levels of mRNA for the heavy and light chains of ferritin were only seen in the
      nrf2-disrupted mice. Transcript levels of UDP-glucuronyl-transferase 1A6, heme
      oxygenase-1, maganese superoxide dismutase, which were inducible in the wild-type
      mice, actually decreased in the mutant mice, whereas levels of mRNA for GST Yc,
      aflatoxin B1 aldehyde reductase and catalase decreased following D3T treatment in
      the mutant mice in the absence of any inductive effect by D3T in the wild-type
      mice. In wild-type mice, treatment with D3T lead to 3-fold increases in hepatic
      Nrf2 mRNA levels within several hours following dosing as assessed by Northern
      blot and RT-PCR analyses. Gel shift analyses with oligonucleotide probes for
      human NQO1 ARE, murine GST Ya ARE, and erythroid transcription factor (NF-E2)
      binding site showed increased intensity of binding with nuclear extracts prepared
      from livers of D3T-treated mice compared to vehicle-treated controls. Antibody to
      Nrf2 supershifted the DNA binding bands of these nuclear extracts. Moreover,
      immunoblot analysis indicated accumulation of Nrf2 in extracts prepared from
      hepatic nuclei of D3T-treated mice at the same time points. CONCLUSIONS: Nrf2
      plays a central role in the regulation of constitutive and inducible expression
      of multiple phase 2 and antioxidative enzymes by chemoprotective dithiolethiones
      in vivo, although patterns of response vary among different genes. Knowledge of
      the factors controlling the specificity of actions of enzyme inducers will be
      exceedingly helpful in the design and isolation of more efficient and selective
      chemoprotective agents.

PMID- 11471549
TI  - Bronchial epithelial cell matrix production in response to silica and basic
      fibroblast growth factor.
AB  - BACKGROUND: Previous studies show that macrophages, lung fibroblasts, and their
      soluble mediators are responsible for the onset and development of pulmonary
      fibrosis. This study was conducted to determine whether airway epithelial cells
      are also directly involved in response to fibrogenic agents and consequently in
      the pathogenesis of lung fibrosis. To verify the hypothesis, we determined
      whether silica acts directly on human bronchial epithelial cells by stimulating
      cytokine and growth factor release and by modifying matrix production. MATERIALS
      AND METHODS: An SV40 large T antigen-transformed human airway epithelial cell
      line, 16HBE14o (16HBE), was used. The expression profile of some proinflammatory
      interleukins (ILs), such as IL-1alpha, IL-1beta and IL-6 and their modulation by
      silica, were evaluated by polymerase chain reaction (PCR) analysis. Transforming
      growth factor beta (TGFbeta) and basic fibroblast growth factor (bFGF) mRNA
      levels were tested by Northern blotting in the presence and in the absence of
      silica. The silica- and/or bFGF-induced effects on matrix components (total
      proteins, collagen, and fibronectin) were also evaluated using radio-labeled
      precursors. RESULTS: The results demonstrated 16HBE internalized silica
      particles. Silica induced a little IL-6 secretion, without affecting IL-1 and
      TGFbeta isoform production and strongly stimulated bFGF mRNA level and bFGF
      protein secretion. Silica also induced changes in 16HBE production of total
      proteins, collagen, and fibronectin production. When added in combination with
      the growth factor, it strengthened bFGF stimulation of matrix component
      secretion. CONCLUSIONS: These results support the hypothesis that the changes in
      matrix components are due to a direct effect of silica on bronchial epithelial
      cells. Silica-induced over-secretion of bFGF suggests that autocrine and
      paracrine differentiation loops for bFGF may also be operative and that these
      mechanisms may be involved in the pathogenesis of pulmonary fibrosis. In the
      future, cytokine-directed therapeutic strategies might find a place in clinical
      practice.

PMID- 11471550
TI  - ARP, a peptide derived from the stress-associated acetylcholinesterase variant,
      has hematopoietic growth promoting activities.
AB  - BACKGROUND: Psychological stress induces rapid and long-lasting changes in blood
      cell composition, implying the existence of stress-induced factors that modulate
      hematopoiesis. Here we report the involvement of the stress-associated
      "readthrough" acetylcholinesterase (AChE-R) variant, and its 26 amino acid C
      terminal domain (ARP) in hematopoietic stress responses. MATERIALS AND METHODS:
      We studied the effects of stress, cortisol, antisense oligonucleotides to AChE,
      and synthetic ARP on peripheral blood cell composition and clonogenic progenitor
      status in mice under normal and stress conditions, and on purified CD34 cells of
      human origin. We employed in situ hybridization and immunocytochemical staining
      to monitor gene expression, and 5-bromo-2-deoxyuridine (BrdU), primary liquid
      cultures, and clonogenic progenitor assays to correlate AChE-R and ARP with
      proliferation and differentiation of hematopoietic progenitors. RESULTS: We
      identified two putative glucocorticoid response elements in the human ACHE gene
      encoding AChE. In human CD34+ hematopoietic progenitor cells, cortisol elevated
      AChE-R mRNA levels and promoted hematopoietic expansion. In mice, a small peptide
      crossreacting with anti-ARP antiserum appeared in serum following forced swim
      stress. Ex vivo, ARP was more effective than cortisol and equally as effective as
      stem cell factor in promoting expansion and differentiation of early
      hematopoietic progenitor cells into myeloid and megakaryocyte lineages.
      CONCLUSIONS: Our findings attribute a role to AChE-R and ARP in hematopoietic
      homeostasis following stress, and suggest the use of ARP in clinical settings
      where ex vivo expansion of progenitor cells is required.

PMID- 11471551
TI  - The transporter associated with antigen processing (TAP): structural integrity,
      expression, function, and its clinical relevance.
AB  - BACKGROUND: The transporter associated with antigen processing (TAP), a member of
      the family of ABC transporters, plays a crucial role in the processing and
      presentation of the major histocompatibility complex (MHC) class I restricted
      antigens. TAP transports peptides from the cytosol into the endoplasmic
      reticulum, thereby selecting peptides matching in length and sequence to
      respective MHC class I molecules. Upon loading on MHC class I molecules, the
      trimeric MHC class I/beta2-microglobulin/ peptide complex is then transported to
      the cell surface and presented to CD8+ cytotoxic T cells. Abnormalities in MHC
      class I surface expression have been found in a number of different malignancies,
      including tumors of distinct histology, viral infections, and autoimmune
      diseases, and therefore represent an important mechanism of malignant or virus
      infected cells to escape proper immune response. In many cases, this
      downregulation has been attributed to impaired TAP expression, which could be due
      to structural alterations or dysregulation. This review summarizes the physiology
      and pathophysiology of TAP, thereby focusing on its function in immune responses
      and its role in human diseases.

PMID- 11471552
TI  - Presence of diabetic complications in type 1 diabetic patients correlates with
      low expression of mononuclear cell AGE-receptor-1 and elevated serum AGE.
AB  - BACKGROUND: Receptors for advanced glycation endproducts (AGE-R) mediate AGE
      turnover, but can also trigger inflammatory genes that promote diabetic tissue
      injury and diabetic complications (DC). High AGE levels and reduced AGE-R sites
      in kidneys of NOD mice prone to type 1 diabetes (T1D) and to renal disease (RD)
      suggested that impaired AGE-R function may contribute to RD in these mice.
      MATERIALS AND METHODS: In this study, after confirming reduced AGE-R1 expression
      in NOD mouse peritoneal macrophages, we tested for differences in AGE-R1, -R2,
      and -R3 gene expression in 54 human subjects by RT-PCR and Western analysis.
      Fresh peripheral blood mononuclear cells (PBMN) were isolated from 36 persons: 18
      T1D patients with severe RD (DC); 11 age-and DM-duration matched patients without
      DC (n-DC); and 7 normal volunteers (NL). EBV-transformed lymphoblasts were
      obtained from an additional 18 subjects (12 T1D patients, 6 with and 6 without
      DC, and 6 nondiabetics). RESULTS: AGE-R1 mRNA and protein of PBMN from n-DC
      patients were enhanced (p < .05 versus NL) in proportion to serum AGE levels
      (sAGE) (p < .005 versus NL). In contrast, PBMN from DC patients exhibited no up
      regulation of AGE-R1 mRNA or protein, despite higher sAGE levels (p < .005 versus
      NL). A similar unresponsiveness in AGE-R1 gene expression was observed in EBV
      transformed lymphoblasts from DC patients versus NL (p < .01), but not in n-DC (p
      = NS). AGE-R2 and -R3 mRNA and protein levels were enhanced in both T1D groups
      (DC > n-DC) (n-DC AGE-R3, p < .05, DC AGE-R3, p < .05) compared to NL. AGE-R2
      mRNA levels correlated with sAGE levels (r = .61, p < .05), and with creatinine
      clearance (r = -.63, p < .05). No differences were noted in AGE-R2 and -R3 mRNA
      expression in cultured cells. CONCLUSIONS: The consistent pattern of elevated
      serum AGE and low expression of AGE-R1 gene in macrophages from T1D mice (NOD),
      fresh PBMN and EBV-transformed cells from T1D patients with advanced DC suggests
      ineffective regulation of R1-mediated AGE turnover, possibly of genetic basis.

PMID- 11471553
TI  - HIV-1 penetrates coronary artery endothelial cells by transcytosis.
AB  - BACKGROUND: The pathogenesis of HIV-1-related cardiomyopathy is poorly
      understood, but HIV-1 has been detected in cardiomyocytes. Whether HIV-1
      penetrates into the myocardium by infection of coronary artery endothelial cells
      (CAEC) or using transcellular or paracellular routes across CAEC has not been
      resolved. MATERIALS AND METHODS: A model of the CAEC barrier was constructed with
      primary CAEC (derived from human coronary vessels). Polymerase chain reaction
      (PCR) assay, infectious assay, and immunofluorescence were employed to show
      abortive nature of HIV-1 infection of CAEC. Tight junction (TJ) and cell adhesion
      proteins were visualized by immunofluorescence. The time course of HIV-1 invasion
      was measured by HIV-1 RNA assay. Inulin permeability assay determined
      paracellular leakage. Transmission electron microscopy demonstrated virus-induced
      endothelial vacuolization. RESULTS: Despite a strong display on CAEC of CXCR4 and
      a lesser expression of CCR3 and CCR5, HIV-1 did not productively replicate in
      CAEC, as shown by infectious assay, immunofluorescence, and electron microscopy.
      HIV-1 infection of CAEC was abortive with minimal reverse transcription of strong
      stop DNA and pol but not full-length or two LTR DNA circles. Upon infection of
      the model with 1 million RNA copies of HIV-1JR-FL, virus penetration 2 hr
      postinfection (PI) was negligible but increased by 1,750% 24 hr PI. The
      paracellular permeability increased during this period by only 25%. Neither AOP
      RANTES nor v-MIPII significantly reduced HIV-1JR-FL invasion. Virus infection did
      not alter the integral TJ protein occludin and the TJ-associated protein ZO-1.
      HIV-1 exposed CAEC and brain microvascular endothelial cells (BMVEC) developed
      extensive cytoplasmic vacuolization with retroviral-like particles in the
      vacuoles. CONCLUSIONS: The endothelium is not an impenetrable barrier to HIV-1.
      The virus opens a transcellular route across coronary and brain endothelia in
      cytoplasmic vacuoles.

PMID- 11471554
TI  - Differential activation of MAP kinase signaling pathways and nuclear factor
      kappaB in bronchoalveolar cells of smokers and nonsmokers.
AB  - BACKGROUND: Prolonged exposure of alveolar macrophages (AM) to components of
      tobacco smoke, including nicotine and aromatic hydrocarbons, may lead to
      alterations in activation of cellular signaling pathways. In this study, we
      compared the spontaneous and LPS-stimulated activation of MAP kinases and NF
      kappaB in bronchoalveolar cells (BAC) from smokers and nonsmokers. MATERIAL AND
      METHODS: BAC, which were predominantly comprised of AM, were obtained by
      bronchoalveolar lavage of healthy volunteering adult smokers and nonsmokers.
      Nuclear and cytoplasmic extracts were prepared from cell lysates. Activation of
      NF-kappaB was assessed by electrophoretic mobility shift assay. Degradation of
      the inhibitor of NF-kappaB (IkappaB) and total MAP kinases were assessed by
      Western blot analysis. Activation of MAP kinases, ERK, SAPK/JNK, and p38 were
      assessed by immunoprecipitation of cell lysates and kinase assays. RESULTS: LPS
      induced the activation of NF-kappaB in a dose-dependent manner, but BAC from
      smokers were approximately 10 times more sensitive, and showed faster kinetics of
      activation of NF-kappaB than BAC from nonsmokers. All three classes of MAP kinase
      ERK, SAPK, and p38-were simultaneously activated by LPS in BAC from smokers and
      nonsmokers. However, the individual MAP kinases exhibited differential kinetics
      of activation. Activation of p38 was more rapid in BAC from smokers, whereas the
      activation of ERK and SAPK was similar in both groups. CONCLUSION: The
      differences in activation of NF-kappaB and MAP kinases in BAC from smokers and
      nonsmokers may relate to the differences in their microenvironment in situ as
      affected by chronic exposure to cigarette smoke. These differences may contribute
      to the increased susceptibility of smokers to infections, including infection
      with HIV-1, and lung disease.

PMID- 11471555
TI  - In vivo gene transfer to dopamine neurons of rat substantia nigra via the high
      affinity neurotensin receptor.
AB  - BACKGROUND: Recently, we synthesized a nonviral gene vector capable of
      transfecting cell lines taking advantage of neurotensin (NT) internalization. The
      vector is NT cross-linked with poly-L-lysine, to which a plasmid DNA was bound to
      form a complex (NT-polyplex). Nigral dopamine neurons are able to internalize NT,
      thus representing a target for gene transfer via NT-polyplex. This hypothesis was
      tested here using reporter genes encoding green fluorescent protein or
      chloramphenicol acetyl transferase. MATERIALS AND METHODS: NT-polyplex was
      injected into the substantia nigra. Double immunofluorescence labeling was used
      to reveal the cell type involved in the propidium iodide-labeled polyplex
      internalization and reporter gene expression. RESULTS: Polyplex internalization
      was observed within dopamine neurons but not within glial cells, and was
      prevented by both hypertonic sucrose solution and SR-48692, a selective
      nonpeptide antagonist of NT receptors. Reporter gene expression was observed in
      dopamine neurons from 48 hr up to 15 days after NT-polyplex injection, and was
      prevented by SR-48692. However, no expression was seen when the NT-polyplex was
      injected into the ansiform lobule of the cerebellum, which contains low- but not
      high-affinity NT receptors. Neither internalization nor expression was observed
      in cultured glial cells, despite the NT-polyplex binding to those cells that was
      prevented by levocabastine, a low-affinity NT receptor antagonist. CONCLUSIONS:
      These results suggest that high-affinity NT receptors mediate the uptake of NT
      polyplex with the subsequent reporter gene expression in vivo. NT polyfection may
      be used to transfer genes of physiologic interest to nigrostriatal dopamine
      neurons, and to produce transgenic animal models of dopamine-related diseases.

PMID- 11471556
TI  - Identification by mRNA differential display of two up-regulated genes as
      candidate mediators of AIDS dementia.
AB  - BACKGROUND: In the dementia associated with acquired immunodeficiency syndrome
      (AIDS), indirect pathomechanisms are important mediators of progressive neuronal
      injury and variable candidate molecules of potential pathogenetic importance have
      been identified. MATERIALS AND METHODS: In an attempt to characterize additional
      mediators of human immunodeficiency virus type 1 (HIV-1)-induced neurotoxicity in
      vivo we have adapted the mRNA differential display technique to monitor the gene
      expression pattern in postmortem cortical tissue from AIDS patients with (n = 7)
      and without (n = 8) cognitive impairment as well as from HIV-1 seronegative
      controls (n = 4). RESULTS: Out of 29 differentially expressed cDNAs, two cDNA
      clones had confirmed variation of transcriptional regulation as assessed by
      reverse Northern analysis and gene-specific reverse transcription polymerase
      chain reaction (RT-PCR) and were up-regulated in the cortex of patients with AIDS
      dementia. Nucleotide sequence analysis of the two cDNAs identified known genes
      not previously associated with the pathogenesis of AIDS dementia, including the
      neurotrophin receptor tyrosine kinase receptor B (TrkB) and the potassium channel
      human open rectifyer K+ channel (ORK) homologous open reading frame (HOHO1).
      CONCLUSIONS: The altered expression of these transcripts may contribute to AIDS
      dementia through the enhancement of microglial activation and immunologic nitric
      oxide synthase (iNOS) activity by abnormal neurotrophic regulation and
      interference with membrane excitability through disturbance of local ion
      homeostasis.

PMID- 11471557
TI  - Examination of the reduced affinity of the thymidylate synthase G52S mutation for
      FdUMP by ab initio and semi-empirical studies.
AB  - BACKGROUND: The G52S mutation in the Arg50 loop of thymidylate synthase leads to
      decreased binding of FdUMP. It has been suggested that the mutation affects the
      Arg50 residue (within the Arg50 loop) responsible for binding the phosphate of
      FdUMP. The binding of the methylguanidinium moiety as a model for Arg50 to a
      methylphosphate entity as a model for FdUMP was investigated with theoretical
      calculations, as well as the structure of the Arg50-Thr51-Gly52 tripeptide in
      comparison with the Arg50-Thr51-Ser52 tripeptide. METHODS: Gaussian-98 and PC
      Spartan programs were used to perform Hartree-Fock and Post-Hartree-Fock quantum
      chemical calculations as well as MNDO (semi-empirical calculations). RESULTS: It
      was found that the strongest binding occurs between the negative methylphosphate
      ion and methylguanidine. The replacement of Gly52 by Ser52 leads to a significant
      displacement of Arg50, which may be responsible for the decreased binding to
      FdUMP. CONCLUSION: The arginine-phosphate binding appears to be geometry
      dependent. Thus, the displacement of the Arg50 residue, as observed in these
      calculated models, upon mutation of Gly52 to Ser may contribute to decreased
      binding of FdUMP to mTS (G52S).

PMID- 11471558
TI  - Presence of DNA fragmentation and lack of neuroprotective effect in DFF45
      knockout mice subjected to traumatic brain injury.
AB  - BACKGROUND: Apoptosis plays an important pathophysiologic role in neuronal cell
      loss and associated neurologic deficits following traumatic brain injury (TBI).
      DNA fragmentation represents one of the characteristic biochemical features of
      neuronal apoptosis and is observed after experimental TBI. DFF45 and DFF40 are
      essential for DNA fragmentation in various models of apoptosis. MATERIALS AND
      METHODS: We used mice deficient in DFF45 and wild-type controls. Oligonucleosomal
      DNA fragmentation induced by TBI was analyzed using in vivo and in vitro assays.
      Expression and integrity of DFF45 and DFF40 proteins was assessed by Western
      analysis. Other outcome measurements included neurologic scoring, learning/memory
      tests, lesion volume measurements (MRI), and assessment of cell viability in
      vitro among others. RESULTS: We compared the effects of controlled cortical
      impact (CCI) trauma in DFF45 knockout mice and wild-type controls. Analysis of
      TBI-induced DNA fragmentation in brain cortex from wild-type and DFF45 knockout
      mice indicates that, although somewhat delayed, oligonucleosomal cleavage of DNA
      occurs after TBI in DFF45 knockout mice. DFF45 knockouts showed no significant
      differences in behavioral outcomes or lesion volumes after TBI as compared to
      wild-type controls. Using an in vitro reconstitution system, we also demonstrated
      that cleavage of DFF45 by caspase-3 is not sufficient for DNA fragmentation
      induced by protein extracts from rat brain cortex. We found that endonuclease
      activity induced in rat brain cortex following TBI depends on the presence of
      Mg2+ and Ca2+, but is not inhibited by Zn2+. Primary neuronal cultures from DFF45
      knockouts failed to show DNA laddering in response to staurosporine, but did show
      prominent, albeit delayed, DNA fragmentation following treatment with etoposide.
      In contrast, primary neurons from wild-type animals demonstrated marked DNA
      fragmentation following treatment with staurosporine or etoposide. CONCLUSIONS:
      The results of this study suggest that, in addition to DFF45/40, other
      endonucleases may be essential for chromatin degradation during neuronal
      apoptosis in adult brain after TBI.

PMID- 11471559
TI  - Introductory experiments in recombinant DNA.
AB  - Nine practical exercises demonstrate the basic principles in recombinant DNA. The
      exercises explain the principles that DNA equals genes and that changes in DNA
      cause changes in genetic properties. The aim is to provide a teaching resource
      that can be used to illustrate the theory and applications of molecular biology
      to highschool students, undergraduate students, medics, dentists, doctors,
      nurses, life scientists, and anyone learning the basics of DNA technology.

PMID- 11471560
TI  - Expressing active ribozymes in cells.
AB  - Artificially engineered ribozymes can be used to specifically regulate expression
      of target genes. Such ribozymes can be synthesized chemically and delivered into
      the cell exogeneously. Alternatively, ribozymes can be produced by the cell
      endogenously, after introduction of the artificial gene into the cellular genome.
      In the latter case, the design of the artificial gene defines the ribozyme
      properties, such as: expression level, intracellular localization, folding and
      association with proteins. Generally speaking, design of the expression vector is
      critical to obtain active ribozyme molecules. This paper first describes factors
      that are known or predicted to affect ribozyme activity in the cell, then reviews
      various expression systems that have been specifically developed for ribozymes.
      Lastly, a recently developed ribozyme system termed snorbozymes (small nucleolar
      RNA:ribozyme hybrids) will be discussed. This powerful test system has generated
      several important observations that are likely to affect the future development
      of ribozyme technology.

PMID- 11471561
TI  - Formation of protease-resistant prion protein in cell-free systems.
AB  - In transmissible spongiform encephalopathies (TSE) or prion diseases, the
      endogenous protease-sensitive prion protein (PrP-sen) of the host is converted to
      an abnormal pathogenic form that has a characteristic partial protease resistance
      (PrP-res). Studies with cell-free reactions indicate that the PrP-res itself can
      directly induce this conversion of PrP-sen. This PrP-res induced conversion
      reaction is highly specific in ways that might account at the molecular level for
      TSE species barriers, polymorphism barriers, and strains. Not only has this
      reaction been observed using mostly purified PrP-sen and PrP-res reactants, but
      also in TSE-infected brain slices. The conversion mechanism appears to involve
      both the binding of PrP-sen to polymeric PrP-res and a conformational change that
      results in incorporation into the PrP-res polymer.

PMID- 11471562
TI  - Redasoft Plasmid 1.1: software for easy, efficient cloning and map drawing.
AB  - A computer program is described which creates circular and linear genetic maps
      with or without sequences, performs restriction analysis, and simulates basic
      molecular cloning operations. Redasoft Plasmid 1.1 is a user-friendly program for
      Windows 95/98/NT/2000, designed to generate high quality genetic maps for
      presentation and publication and to aid the molecular biologist in selecting
      restriction endonucleases for common molecular cloning experiments. The program
      incorporates an integrated web browser and can automatically generate complete,
      labeled maps from sequences on the Internet.

PMID- 11471563
TI  - Genetic modification of intestinal lactobacilli and bifidobacteria.
AB  - Lactobacilli and bifidobacteria are important members of the gastrointestinal
      microflora of man and animals. There is a substantial and growing body of
      evidence that these microbes provide benefits to the host in which they reside.
      Understanding the roles of these two groups of bacteria in the intestine
      continues to be a significant challenge. To this end, genetic characterisation
      and manipulation of intestinal lactobacilli and bifidobacteria is essential to
      define their contributions to the intestinal microflora, and to potentially
      exploit any beneficial or unique properties. This review will describe the tools
      and strategies currently available for the genetic manipulation of lactobacilli
      and bifidobacteria. Additionally, the ramifications and opportunities that may
      arise as a result of the genetic manipulation of probiotic lactobacilli and
      bifidobacteria will be addressed.

PMID- 11471564
TI  - [URE3] and [PSI] are prions of yeast and evidence for new fungal prions.
AB  - [URE3] and [PSI] are two non-Mendelian genetic elements discovered over 25 years
      ago and never assigned to a nucleic acid replicon. Their genetic properties led
      us to propose that they are prions, altered self-propagating forms of Ure2p and
      Sup35p, respectively, that cannot properly carry out the normal functions of
      these proteins. Ure2p is partially protease-resistant in [URE3] strains and
      Sup35p is aggregated specifically in [PSI] strains supporting this idea.
      Overexpression of Hsp104 cures [PSI], as does the absence of this protein,
      suggesting that the prion change of Sup35p in [PSI] strains is aggregation.
      Strains of [PSI], analogous to those described for scrapie, have now been
      described as well as an in vitro system for [PSI] propagation. Recently, two new
      potential prions have been described, one in yeast and the other in the
      filamentous fungus, Podospora.

PMID- 11471565
TI  - The use of ribozyme gene therapy for the inhibition of HIV replication and its
      pathogenic sequelae.
AB  - Human immunodeficiency virus (HIV) is a lentivirus, a separate genus of the
      Retroviridae which are RNA viruses that integrate as DNA copies into the genomes
      of host cells and replicate intracellularly through various RNA intermediates.
      Several of these RNA molecules can be targeted by ribozymes and a number of
      investigators, including our group, have demonstrated the ability of ribozymes to
      suppress HIV replication in cultured cells. It is argued that the use of this
      ribozyme gene therapy approach for the treatment of HIV infection may act as an
      adjunct to chemotherapeutic drugs and may affect not just viral suppression, but
      also immune restoration. This approach can be tested in Clinical Trials, several
      of which are currently under way.

PMID- 11471566
TI  - Proinflammatory cytokine expression contributes to brain injury provoked by
      chronic monocyte activation.
AB  - BACKGROUND: We have proposed that an increased interaction between
      monocyte/macrophages and blood vessel endothelium predisposes subjects to
      strokes. The effect of chronic monocyte activation on the development of cerebral
      infarcts was thus studied in rats after provocation of a modified local Swartzman
      reaction, in brain vasculature. MATERIALS AND METHODS: Two weeks after an IV
      bolus of bacillus Calmette-Guerin (BCG), we studied spontaneous superoxide
      production, integrin expression, endothelial adhesion of monocytes and the
      neurological symptoms, brain histology, and cytokine immunoreactivity after a
      provocative dose of LPS (30-300 microg/rat i.c.v.). RESULTS: Monocyte migration
      into the brain was stimulated by BCG priming. The incidence of paralysis and
      death in response to LPS was markedly increased in BCG-primed rats. Histological
      evaluation of the brains of neurologically impaired and moribund animals revealed
      intravascular thrombosis and pale and hemorrhagic infarcts. Infiltrates of
      leukocytes expressing immunoreactive IL-1:, IL-6, and TNF-alpha were found around
      blood vessels, cerebral ventricles, and meninges, and were accompanied by a
      profound microglial expression of IL1P, endothelial expression of IL-6, and
      expression of TNF-alpha and TNF-R 1 in glia and neurons of cortex and
      hippocampus. Treatment (2 x 100 microg/10 ,I, i.c.v.) with recombinant human (rh
      )TNF 55kDa receptor completely prevented, and treatment with rh-IL- I receptor
      antagonist significantly decreased the incidence of paralysis and death in
      response to BCG + LPS. The improvement of neurological symptoms was accompanied
      by reduced histological damage and supppression of IL-1P/ expression in the brain
      tissue. CONCLUSIONS: The data demonstrate that chronic monocyte activation
      predisposes subjects to thrombosis and hemorrhage via an exaggerated release of
      proinflammatory cytokines.

PMID- 11471567
TI  - Antigen-specific IgG antibodies in stage IV long-time survival breast cancer
      patients.
AB  - BACKGROUND: Profiling the immune responses in patients with cancer is expected to
      facilitate the design of diagnostic tests and therapeutic vaccines. Such studies
      usually require the parental antigens. We attempted to profile the immune
      responses in patients with breast cancer using a peptide phage display selection
      strategy, which identifies antibody specificities whether or not the antigens are
      known. MATERIALS AND METHODS: A panel of random peptide phage libraries was
      panned on serum IgG antibodies from breast cancer patients with stage IV, seeking
      for disease specific IgG epitopes. ELISA, immunoscreening, and Western blotting
      techniques were the main approaches used. RESULTS: Phage-displayed peptides were
      specifically enriched for binding to IgG antibodies from patients with breast
      cancer. Several peptides have been identified, in particular the SQRIPARIHHFPTSI
      peptide, which was recognized by IgG antibodies from breast cancer patients, but
      not from normals (p < 0.0004). In patients who responded to the selected
      peptides, in particular the SQRIPARIHHFPTSI peptide, antibodies against a 66 kDa
      cellular protein were found. Interestingly, three out of six patients with the
      strongest immunoreactivity are still alive, with a mean survival time from first
      recurrence until now of 2553 days. In contrast, all the nonresponders (n = 10)
      are deceased. The mean survival time of these patients was 784 days, whereas the
      mean survival time of the three deceased responders was 1050 days (p < 0.02).
      CONCLUSIONS: The data provide the first example in which panning of peptide phage
      display libraries on patient IgG antibodies results in the isolation of breast
      cancer specific IgG epitopes, some of which correlate with patient survival time.
      Thus, the identified B-cell epitopes should be of great interest in vaccine
      development.

PMID- 11471568
TI  - Compartmentalization of vascular endothelial growth factor to the epithelial
      surface of the human lung.
AB  - BACKGROUND: Based on assessment of mRNA expression, the lung is a major site of
      expression of the vascular endothelial growth factor (VEGF) gene, largely from
      type II alveolar epithelial cells. With the knowledge that VEGF can function to
      induce vascular leak, we hypothesized that to protect the lung from pulmonary
      edema, the VEGF produced in the lung must be compartmentalized from the pulmonary
      endothelium, and thus must be compartmentalized to the surface of the respiratory
      epithelium. MATERIAL AND METHODS: To assess this hypothesis, we quantified the
      levels of VEGF in human respiratory epithelial lining fluid recovered by
      bronchoalveolar lavage from normal individuals. RESULTS: Strikingly, human
      respiratory epithelial lining fluid contains 11 +/- 5 ng/mL as quantified by
      ELISA, a 500-fold greater concentration than plasma (22 +/- 10 pg/mL, p <
      0.0005). Western analysis of BAL fluid proteins showed the major VEGF isoform in
      respiratory epithelial lining fluid is VEGF165. CONCLUSIONS: With the knowledge
      that proteins of molecular mass like VEGF (34 to 46 kDa) slowly diffuse across
      the alveolar epithelium, it is likely that this high level "reservoir" of VEGF
      protein on the respiratory epithelial surface plays a role in normal lung
      endothelial biology. However, this compartmentalized VEGF reservoir may also be a
      "Damocles sword" poised to induce lung endothelial permeability in conditions of
      acute lung injury when the integrity of the alveolar epithelial barrier is
      breached.

PMID- 11471569
TI  - Induction of biologically active antibodies in mice, rabbits, and monkeys by
      Plasmodium falciparum EBA-175 region II DNA vaccine.
AB  - BACKGROUND: Plasmodium falciparum merozoites bind to and invade human
      erythrocytes via specific erythrocyte receptors. This establishes the
      erythrocytic stage of the parasite life cycle that causes clinical disease
      resulting in 2-3 million deaths per year. We tested the hypothesis that a
      Plasmodium falciparum ligand, EBA-175 region II (RII), which binds its
      erythrocyte receptor glycophorin A during invasion, can be used as an immunogen
      to induce antibodies that block the binding of RII to erythrocytes and thereby
      inhibit parasite invasion of erythrocytes. Accordingly, we immunized mice,
      rabbits, and monkeys with DNA plasmids that encoded the 616 amino acid RII.
      MATERIALS AND METHODS: DNA vaccine plasmids that targeted the secretion of
      recombinant RII protein with and without the universal T-cell helper epitopes
      P2P30 were used to immunize mice, rabbits, and Aotus monkeys. RII specific
      antibodies were assessed by IFA, ELISA, blocking of native [35S] labeled EBA-175
      binding to human erythrocytes, and growth inhibition assays, all in vitro.
      RESULTS: The RII DNA plasmids were highly immunogenic as measured by ELISA and
      IFA. The anti-RII antibodies blocked the binding of native EBA-175 to
      erythrocytes, and rosetting of erythrocytes on COS-7 cells expressing RII. Most
      important, murine and rabbit anti-RII antibodies inhibited the invasion of
      merozoites into erythrocytes. We immunized nonhuman primates and showed that the
      RII-DNA plasmids were immunogenic and well tolerated in these monkeys. Monkeys
      were challenged with parasitized erythrocytes; one of three monkeys that received
      RII DNA plasmid was protected from fulminant disease. After challenge with live
      parasites, anti-RII antibody titers were boosted in the immunized monkeys.
      CONCLUSIONS: By proving the hypothesis that anti-RII antibodies can block
      merozoite invasion of erythrocytes, these studies pave the way for the clinical
      evaluation of EBA-175 as a receptor-blockade vaccine.

PMID- 11471570
TI  - Genetic determinants of ethanol-induced liver damage.
AB  - BACKGROUND: Although a clear correlation exists between cumulative alcohol intake
      and liver disease, only some of the alcohol abusers develop signs of ethanol
      induced liver damage. To identify some of the genetic variations predisposing
      persons to alcoholic liver disease (ALD), a genetic study was performed in heavy
      drinkers from the cohort of the Dionysis study, a survey aimed at evaluating
      liver disease in the open population of two towns in Northern Italy (6917
      individuals). MATERIALS AND METHODS: 158 heavy drinkers (approximately 85% of all
      heavy drinkers in the population; daily alcohol intake > 120 g in males and >60 g
      in females) were investigated by the analysis of nine polymorphic regions,
      mapping in exons III and IX of the alcohol-dehydrogenase (ADH)-2 gene, in exon
      VIII of the ADH3 gene, in intron VI, in the promoter region of the cytochrome
      P4502E1 (CYP2E1) gene, and in the promoter region of the tumor necrosis factor
      alpha gene. RESULTS: Heavy drinkers with or without ALD significantly differed
      for the distribution of alleles of the cytochrome P4502E1 (CYP2E1) and alcohol
      dehydrogenase-3 (ADH-3) genes. In one town, allele C2 in the promoter region of
      the CYP2E1 gene had a frequency of 0.06 in healthy heavy drinkers, of 0.19 in
      heavy drinkers with ALD (p = 0.012), and of 0.33 in heavy drinkers with cirrhosis
      (p = 0.033). In the other town, whose inhabitants have different genetic
      derivation, a prominent association between ALD and homozygosity for allele
      ADH3*2 of ADH3 was found, with a prevalence of 0.31 in heavy drinkers with ALD
      and of 0.07 in healthy heavy drinkers controls (p = 0.004). CONCLUSIONS. Both
      heterozygosity for allele C2 of CYP2E1 and homozygosity for allele ADH3*2 of ADH3
      are independent risk factors for ALD in alcohol abusers. The relative
      contribution of these genotypes to ALD is dependent on their frequency in the
      population. Overall, heavy drinkers lacking either of these two genotypes are 3.2
      and 4.3 times more protected from developing ALD and cirrhosis respectively.

PMID- 11471571
TI  - All trans-retinoic acid selectively down-regulates matrix metalloproteinase-9
      (MMP-9) and up-regulates tissue inhibitor of metalloproteinase-1 (TIMP-1) in
      human bronchoalveolar lavage cells.
AB  - BACKGROUND: The balance between proteinases and antiproteinases plays an
      important role in tissue destruction and remodelling. In chronic obstructive
      pulmonary disease (COPD) and emphysema, an imbalance between matrix
      metalloproteinases (MMPs) and inhibitors of tissue metalloproteinase (TIMPs) has
      been reported. Alveolar macrophages are considered to be the main source of MMPs.
      We therefore have analyzed the effects of free and liposomal all trans-retinoic
      acid (ATRA) on the expression of MMP-9 and TIMP-1 in bronchoalveolar lavage (BAL)
      cells from patients with COPD and patients with other lung diseases. MATERIAL AND
      METHODS: BAL cells were incubated 1-3 day with either liposomal or free ATRA.
      Supernatants were tested for MMP-9 and TIMP-1 protein in specific ELISA systems;
      mRNA analysis was performed by semi-quantitative RT-PCR and by quantitative
      LightCycler PCR. RESULTS: We demonstrate that either liposomal or free ATRA
      selectively down-regulates MMP-9 and up-regulates TIMP-1. At the protein level,
      MMP-9 is decreased 3-fold and TIMP-1 is increased 3.5-fold compared to the base
      line with empty liposomes or untreated cells. The ratio of MMP-9 and its
      inhibitor TIMP-1, which may be crucial to the overall proteolytic potential
      decreased by factor 8. That this countercurrent effect of ATRA is not due to an
      altered protein stability but to transcriptional regulation could be demonstrated
      by RT-PCR. Quantitative LightCycler analysis revealed a 2.5-fold decrease of MMP
      9 mRNA and a 4.5 fold increase of TIMP- 1 mRNA. CONCLUSIONS: These data suggest
      that ATRA treatment via its impact on the proteinase/antiproteinase ratio may
      become a new therapeutic strategy for patients with inflammatory destructive lung
      diseases.

PMID- 11471573
TI  - High points in the history of Lymphology 1602-2001.

PMID- 11471572
TI  - Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for
      cancer gene therapy.
AB  - BACKGROUND: The mda-7 gene (melanoma differentiation associated gene-7) is a
      novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been
      previously reported. In this report, we analyze the anti-tumor efficacy of Ad
      mda7 in a broad spectrum of cancer lines. MATERIALS AND METHODS: Ad-mda7
      transduced cancer or normal cell lines were assayed for cell proliferation
      (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue
      exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by
      fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium
      Iodide staining and FACs analysis). RESULTS: Ad-mda7 treatment of tumor cells
      resulted in growth inhibition and apoptosis in a temporal and dose-dependent
      manner. The anti-tumor effects were independent of the genomic status of p53, RB,
      p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did
      not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover,
      Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus,
      Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a
      variety of cancers. CONCLUSIONS: The potent and selective killing activity of Ad
      mda7 in cancer cells but not in normal cells makes this vector a potential
      candidate for cancer gene therapy.

PMID- 11471574
TI  - Identification of pelvic lymph nodes with chlorophyllin after injection into the
      uterine cervix: an experimental and clinical study.
AB  - We investigated the value of staining retroperitoneal lymph nodes with
      chlorophyllin in normal dogs and in women with malignant uterine tumors
      undergoing lymphadenectomy. In dogs, after 0.3% chlorophyllin (sodium copper
      chlorophyllin) was injected into the canine uterus, the concentration of dye in
      the bloodstream was measured with a spectrophotometer and sections of stained
      retroperitoneal lymph nodes were examined using light and electron microscopy.
      The highest blood levels were detected at 4 hrs and nearly all of the
      chlorophyllin was gone from the bloodstream by 18 hrs but was retained in nodal
      macrophages for at least 4 days. No morphological changes were found in the
      excised lymph nodes. Twenty-four patients with cervical carcinoma and 20 patients
      with endometrial carcinoma undergoing radical hysterectomy and lymphadenectomy
      were divided into a lymphatic coloration group (23 patients) and a non-coloration
      (control) group (21 patients). In the lymphatic coloration group (0.3%
      chlorophyllin) was injected into the cervix 5 days before elective
      lymphadenectomy. There were no complications attributed to injection of the
      chlorophyllin. The number of dissected lymph nodes in the coloration group were
      greater than the control group (p<0.01) and the time of operation was shorter
      (p<0.01). These results suggest that chlorophyllin is safe and facilitates
      identification of retroperitoneal lymph nodes, allows more complete nodal
      excision and shortens the time of operation in patients undergoing radical
      hysterectomy with lymphadenectomy.

PMID- 11471575
TI  - Histomorphologic reaction patterns in cervical lymph nodes of different neck
      sites.
AB  - Immunologically based studies of host-tumor interactions have gained popularity
      in head and neck oncology and histopathological determination of lymph node
      reactivity has been shown to correlate with survival. However, little is known
      about lymph node reaction patterns in the "normal" neck. In a prospective
      histomorphologic study 1,024 cervical lymph nodes (CLN) were dissected at autopsy
      from 25 selected cadavers free of head and neck disease. To investigate regional
      differences of immune reactivity, these lymph nodes were grouped according to
      neck levels. 242 CLN groups of 50 neck sites were microscopically classified into
      one of four distinct histomorphologic immune reaction patterns (RP). 14.5% of CLN
      groups showed lymphocyte predominance (RP 1), 12% showed germinal center
      predominance (RP 2), 63.2% were unstimulated (RP 3) and 10.3% displayed
      regressive changes (RP 4). Distribution of RP was highly significant according to
      neck level (p<0.001): RP 1 and RP 2 were common in the submandibular (Level I)
      and the upper parajugular groups (Level II) whereas RP 4 was more typical in the
      inferior parajugular groups (Level IV) and posterior triangle (Level V). RP 2 and
      RP 4 showed significant correlation to age and general condition. These findings
      suggest that tumor independent lymph node reactivity related to neck site, age
      and general condition of the patient needs to be differentiatedfrom tumor induced
      patterns in future morphologic investigations of cervical lymph nodes in patients
      with head and neck carcinoma.

PMID- 11471576
TI  - The diagnosis and treatment of peripheral lymphedema: draft revision of the 1995
      Consensus Document of the International Society of Lymphology Executive Committee
      for discussion at the September 3-7, 2001, XVIII International Congress of
      Lymphology in Genoa, Italy.

PMID- 11471577
TI  - Unilateral versus bilateral acupuncture on knee function in advanced
      osteoarthritis of the knee--a prospective randomised trial.
AB  - We report a prospective randomised trial of acupuncture given to 44 patients with
      advanced osteoarthritis (OA) of the knee awaiting total knee joint replacement.
      Patients were randomly allocated into two groups, group A receiving acupuncture
      to the most affected knee only and group B receiving acupuncture to both knees.
      Acupuncture was given to four local points around the knee and one distal point.
      The local points were Spleen 9 (Yinlinquan, SP9), Spleen 10 (Xuehai, SP10),
      Stomach 34 (Liangqui, ST34), and Stomach 36 (Zusanli, ST36). The distal point was
      Large Intestine 4 (Hegu, LI4) on the first web space of the ipsilateral hand. A
      blinded observer assessed knee function before starting treatment, and at the end
      of two and six months. Analysis of the results showed a significant reduction in
      symptoms in both groups, and this improvement was sustained for six months. There
      was no statistically significant difference between the groups. In conclusion,
      unilateral acupuncture is as effective as bilateral acupuncture in increasing
      function and reducing the pain associated with OA of the knee. This trial is not
      able to distinguish the specific from the non-specific effects of the treatment.

PMID- 11471578
TI  - A comparison of acupuncture with advice and exercises on the symptomatic
      treatment of osteoarthritis of the hip--a randomised controlled trial.
AB  - Acupuncture is becoming a common technique within the physiotherapy profession as
      a treatment modality for pain relief; however, few randomised controlled trials
      have been undertaken to assess the effectiveness of acupuncture, particularly in
      the treatment of osteoarthritis (OA) of the hip. Therefore, a randomised trial to
      compare the effectiveness of acupuncture with advice and exercises on the
      symptomatic treatment of OA of the hip was carried out. Thirty-two patients
      awaiting a total hip arthroplasty were randomly allocated to either the
      experimental group, (A), to have six sessions of acupuncture each lasting up to
      25 minutes, or the control group, (B), to be given advice and exercises for their
      hip over a six week period. Group A consisted of three men and 13 women, and
      group B consisted of four men and eight women. The average age in group A was 66
      years and in group B it was 68 years. Patients were assessed for pain and
      functional ability, using a modified version of the WOMAC questionnaire, pre
      treatment, immediately post-treatment and at eight weeks post-treatment. The pre
      treatment WOMAC scores in the two groups were similar (p=0.85). There was a
      significant improvement in group A (decrease in WOMAC score) immediately post
      treatment (p=0.002) and this was maintained at the eight-week follow-up (p=0.03).
      There were no significant changes in group B. When the changes in WOMAC scores
      were compared between groups, a significantly greater improvement was found
      between pre-treatment and immediately post-treatment in group A, compared with
      group B (p=0.02). The changes between pre-treatment and the eight-week follow-up
      also showed a significant improvement in group A compared with group B (p=0.03).
      In conclusion, this trial supports the hypothesis that acupuncture is more
      effective than advice and exercises in the symptomatic treatment of OA of the
      hip.

PMID- 11471579
TI  - The needle and the lancet: acupuncture in Britain, 1683-2000.
AB  - Although commonly regarded as a late twentieth century phenomenon, acupuncture
      use in Britain has a surprisingly long history, beginning with its seventeenth
      century transmission from China and Japan. Acupuncture was in use in the great
      hospitals of Paris before a second stage of transmission and translation brought
      it to nineteenth century Britain. Acupuncture's first wave of popularity and its
      results in British medical practice can be examined through examples drawn from
      the Lancet, the BMJ and other medical periodicals. This historical transmission
      of acupuncture to the UK can be fruitfully compared to its modern analogue, and
      historical patterns of acupuncture use can be compared with those displayed in
      contemporary Britain.

PMID- 11471580
TI  - Developments in veterinary acupuncture.
AB  - Veterinary acupuncture has been developing rapidly in recent years. Public
      attention has been focused on acupuncture as a possible therapeutic intervention
      for their pets by the media. Interest in acupuncture from the veterinary
      profession has therefore been primarily driven by owner demand. Veterinarians are
      now seeking courses in acupuncture that are relevant to themselves as general
      practitioners rather than as specialists in complementary medicine. Evidence of
      the efficacy of acupuncture in treating any of the veterinary species is limited,
      so it is significant that two acupuncture-related trials at Glasgow University
      Veterinary School are currently receiving funding.

PMID- 11471581
TI  - Percutaneous electrical nerve stimulation--electroacupuncture by another name? A
      comparative review.
AB  - Percutaneous electrical nerve stimulation (PENS) is a technique that has been
      described as a 'novel analgesic therapy'. A review was performed of the published
      literature in order to compare PENS with the author's knowledge and experience of
      the use of EA, specifically with regard to the stimulation parameters, the
      selection of points, and the reported efficacy. The conclusion of the review is
      that PENS is neither different in principle nor in practice from EA, and whilst
      the term accurately reflects the nature of the treatment, there is no substantial
      justification for referring to PENS as a novel therapy.

PMID- 11471582
TI  - An audit of acupuncture in a single-handed general practice over one year.
AB  - An audit was performed over one year on all patients undergoing acupuncture for a
      variety of conditions in a single-handed GP practice. The patients were observed
      for a further year to assess the effectiveness and duration of the treatment
      effect. Using the 'measure yourself medical outcome profile' (MYMOP)
      questionnaire, the effectiveness of acupuncture treatment was measured, and
      patients were categorised into no effect, improved or much improved. A total of
      140 patients were audited over the one-year period. No effect was seen in 31% of
      patients, a further 31% were improved, and 38% were much improved. Those with a
      shorter duration of symptoms appeared to show the most benefit. During the one
      year post-treatment observation period 50% of patients required further
      treatment. In conclusion, acupuncture appears to have been an effective treatment
      in the author's General Practice population. In this audit acupuncture seems to
      have had a short duration of effect. It is believed that this has lead to an
      increase in workload, not only as a result of patient demand, but also due to
      recurrence of symptoms following the initial success of treatment.

PMID- 11471583
TI  - An audit of the impact of introducing microacupuncture into primary care.
AB  - In 1997, one of the partners in a general practice in NW London comprising 6,700
      patients began using microacupuncture--a very brief form of treatment described
      by Felix Mann. The computer system used for patient records was modified to allow
      easy recording of details of acupuncture treatments; the latter being performed
      opportunistically in standard 10-minute consultations. Over the course of three
      years, during which time a second partner began using acupuncture, referrals to
      acute physiotherapy (conditions present for < 3 months) fell by 86%, and
      referrals to outpatient rheumatology fell by 51%. This is likely to represent a
      considerable cost saving to the NHS.

PMID- 11471584
TI  - Repetitive epileptic fits--a possible adverse effect after transcutaneous
      electrical nerve stimulation (TENS) in a post-stroke patient.
AB  - A case of repetitive epileptic fits in a post stroke patient after transcutaneous
      electrical nerve stimulation (TENS) is presented. It seems more likely than not
      that the TENS triggered the repetitive fits in this patient. Although the risk of
      this adverse effect seems to be small, it should be borne in mind when TENS is
      used in a post-stroke patient. Since TENS is now used commonly in post-stroke
      patients, this problem is worthy of further study.

PMID- 11471585
TI  - No difference between acupuncture and sham in chronic tension-type headache
      (n=39).

PMID- 11471586
TI  - Hand acupressure reduces postoperative vomiting after strabismus surgery (n=50).

PMID- 11471587
TI  - Electroacupuncture is effective for control of myeloablative chemotherapy-induced
      emesis (n=104).

PMID- 11471588
TI  - EA for wobbler syndrome in dogs (n=40).

PMID- 11471589
TI  - A cocktail stick is as good as brief acupuncture in episodic tension-type
      headache (n=50).

PMID- 11471590
TI  - Survey of adverse events in Australia (n=1100).

PMID- 11471591
TI  - Acupuncture and experimentally induced ishaemic pain (n=60).

PMID- 11471592
TI  - Acupuncture influences cortical blood flow in rats (n=52).

PMID- 11471593
TI  - East and west see eye to eye--an elective report.
AB  - A summary of personal experiences encountered as a medical student on elective at
      an eye hospital in China. It bears witness to the possibility of seamless
      combination of western and traditional Chinese medical practices in the field of
      ophthalmology. Included are also the acupuncture points used in the treatment of
      optic atrophy at this particular eye hospital. Address of eye hospital: Zhongshan
      Ophthalmic Center 54 South Xianlie Road Guangzhou 510060 China Period of
      elective: 5th January 2001-11th March 2001.

PMID- 11471594
TI  - Travels in Japan.
AB  - Following his attendance at the ICMART meeting, in Myasaki in 1988, the author, a
      BMAS member, resolved to revisit Japan. He found that acupuncture was widely
      practised throughout the country; although the patients were in the main elderly.
      The range of techniques used ranged from TCM to western, and broadly mirrored the
      styles practised in the West. Most young people in Japan considered acupuncture
      to be rather old fashioned, and it is postulated that this contrasts with the
      population seeking complementary medicine in the West.

PMID- 11471595
TI  - Reusable acupuncture needles are a potential risk for transmitting Prion disease.

PMID- 11471596
TI  - Cross-sectional imaging patterns of desmoplastic fibroma.
AB  - The aim of this study was to work out the cross-sectional imaging characteristics
      of desmoplastic fibroma (DF). In 3 patients with histologically proven DF, the
      imaging characteristics obtained with cross-sectional techniques were reviewed
      retrospectively. Radiographs and CT scans were available in all patients, and
      plain and contrast-enhanced MR examinations in 2 patients. Compared with
      conventional radiographs, CT allowed more accurate assessment of the extent of
      bone destruction including cortical breakthrough and articular invasion.
      Intramedullary tumor growth and soft tissue extension was best detected with MRI.
      Apart from heterogeneity on MR images, DF displayed nonspecific low signal
      intensity on unenhanced T1-weighted images and an intermediate to high signal
      intensity including areas of low intensity on T2-weighted images. Desmoplastic
      fibroma showed a distinct, inhomogeneous gadolinium enhancement. Although cross
      sectional imaging features of DF are nonspecific, some MR characteristics, such
      as inhomogeneous contrast enhancement and the presence of low-intensity regions
      on T2-weighted images, are helpful in determining the differential diagnosis.
      Cross-sectional imaging of DF is useful for local staging of the tumor because it
      provides valuable information about the extent of bone destruction as well as
      medullary and extraosseous spread.

PMID- 11471597
TI  - Power Doppler ultrasonography for the evaluation of skin tumors other than
      malignant melanoma.
AB  - The purpose of this prospective study was to evaluate the value of power Doppler
      ultrasonography (PDUS) in assessing the vascularity of skin tumors other than
      malignant melanoma, and to investigate possible diagnostic criteria to help to
      distinguish malignant from benign tumors preoperatively. Seventy-one patients
      with the clinical diagnosis of a skin tumor were initially evaluated by
      ultrasonography. Then PDUS was performed and the presence and type of vascularity
      (peripheral or mixed) were investigated. Of the 19 benign and 52 malignant
      lesions, 3 could not be visualized with US. Forty-nine lesions were found to have
      vascularity (21 peripheral, 28 mixed-type) on PDUS. Of the malignant lesions, 26
      showed mixed and 17 showed peripheral-type vascularity; for benign lesions these
      numbers were 2 and 4 respectively. The presence of vascularity correlated well
      with pathological behavior (malignant versus benign) (P = 0.00002), width (P =
      0.0001), thickness (P = 0.001), dermal disruption (P = 0.0018), and subdermal
      extension (P = 0.002) of the tumor; however, the type of vascularity correlated
      only with thickness (P = 0.014). In relation to malignancy, the sensitivity of
      the presence of vascularity on PDUS was 88% and the specificity was 63%. These
      values were 93% and 40% respectively, for the mixed type of vascularity when it
      was accepted as a feature of malignancy. PDUS may help to distinguish malignant
      from benign skin tumors during preoperative evaluation.

PMID- 11471598
TI  - Broadband ultrasound attenuation imaging: influence of location of region of
      measurement.
AB  - The aim of the study was to investigate the effect of three different regions of
      interest (ROIs) varying in size and shape on broadband ultrasound attenuation
      (BUA) measurements of the calcaneus. Two hundred and sixty-five postmenopausal
      Caucasian women participated in this study. In 43 women osteoporotic fractures
      were documented on spinal radiographs. Bone mineral density (BMD) measurements of
      the lumbar spine and the femur were made using dual-energy X-ray absorptiometry.
      BUA measurements were obtained at a circular ROI automatically determined by the
      imaging system (ROIc), at a manually traced irregular ROI encompassing the
      posterior part of the calcaneus (ROIi), and at an anatomical square ROI located
      in the posterior part of the calcaneus (ROIs). Reproducibility was better in ROIc
      than in ROIi and ROIs. High correlations were found between BUA measurements with
      ROIc and ROIs (r = 0.981, P < 0.0001) as well as between those with ROIc and ROIi
      (r = 0.965, P < 0.0001). There were no significant differences between the
      correlations of BUA with axial BMD at ROIc compared with ROIi and ROIs. No
      significant difference was found between the areas under the ROC curve at ROIi,
      ROIc, and ROIs for women with fractures. The results show that superior
      reproducibility makes ROIc the most appropriate region of BUA measurement in a
      comparison with ROIi and ROIs.

PMID- 11471599
TI  - Magnetic resonance imaging appearances of different discovertebral lesions.
AB  - Magnetic resonance imaging (MRI) is not only an excellent imaging modality for
      the demonstration of morphological changes but is also capable of providing
      pathophysiological and pathoanatomic information about various spinal diseases.
      Different techniques offer opportunities to demonstrate the degree of water
      content, the vascularity of tissue components, the accumulation of fat, and new
      bone production. Thus MRI closely reflects the initial phase as well as the
      progression of pathoanatomic changes during the evolution of a disease. Due to
      the high sensitivity of MRI, abnormalities are often established at an early
      stage of discovertebral disease, when etiological diagnosis may be difficult. The
      specificity of MRI findings lags behind its sensitivity; similar changes can be
      demonstrated in etiologically different disease entities, which reflects the
      limited reactive possibilities of the osteoarticular system. In fact, the MRI
      morphological and signal intensity features of different discovertebral lesions
      are commonly determined more by their location and by the reactive capabilities
      of disc and bone than by their etiology. Early and exact MRI differentiation of
      various discovertebral lesions is of the utmost clinical importance for prompt
      institution of appropriate therapy.

PMID- 11471600
TI  - Dorsal defect on a multi-partite patella: imaging findings.
AB  - Coincidence of dorsal defect on a multipartite patella constitutes a rare cause
      of anterior knee pain in the first decades of life. Imaging findings of this
      uncommon symptomatic skeletal variant are discussed, with emphasis on MR
      features.

PMID- 11471601
TI  - Evaluation of image quality and dose in renal colic: comparison of different
      spiral-CT protocols.
AB  - The aim of this study was to test different technical spiral-CT parameters to
      obtain optimal image quality with reduced X-ray dose. Images were acquired with a
      spiral-CT system Philips Tomoscan AVE1, using 250 mA, 120 kV, and 1-s rotational
      time. Three protocols were tested: protocol A with 5-mm thickness, pitch 1.6,
      slice reconstruction every 2.5 mm; protocol B with 3-mm thickness, pitch 1.6,
      slice reconstruction every 1.5 mm; and protocol C with 3-mm thickness, pitch 2,
      slice reconstruction every 1.5 mm. Two phantoms were employed to evaluate the
      image quality. Axial images were acquired, then sagittal and coronal images were
      reconstructed. Finally, the absorbed X-ray dose for each protocol was measured.
      Regarding image quality, 5-mm-thick images (protocol A) showed greater spatial
      resolution and lower noise compared with 3-mm-thick images (protocols B and C) on
      the axial plane; 3-mm reconstructed sagittal and coronal images (protocols B and
      C) showed an improved image quality compared with 5-mm reformatted images
      (protocol A). Concerning X-ray dose, the mean dose was: protocol A 19.6 +/- 0.8
      mGy; protocol B 14.4 +/- 0.6 mGy; protocol C 12.5 +/- 1.0 mGy. Our study supports
      the use of thin slices (3 mm) combined with pitch of 1.6 or 2 in renal colic for
      X-ray dose reduction to the patient and good image quality.

PMID- 11471602
TI  - Malignant mixed mullerian tumor of the ovary: imaging findings.
AB  - OBJECTIVE: We describe the imaging findings of malignant mixed mullerian tumor
      (MMMT) of the ovary, which have not previously been reported. MATERIALS AND
      METHODS: We experienced 13 cases of ovarian MMMT in eight patients. All patients
      underwent surgical resection and the MMMTs were confirmed pathologically. US (n =
      8), CT (n = 8), and MRI (n = 1) examinations were performed before operation.
      Imaging features were analyzed retrospectively for bilaterality, tumor solidity
      (cystic or solid), size, and contrast enhancement of the tumor on CT and MRI.
      Presence of ascites and other evidence of peritoneal seeding, adjacent organ
      invasion, distant metastasis, and surgical staging were also evaluated. RESULTS:
      There were bilateral ovarian MMMTs in five patients and unilateral MMMTs in three
      patients. Two of the MMMTs were multiseptated cystic, and 11 were mixed (solid
      and cystic). The diameter of the largest dimension was less than 5 cm in one
      case, 5-10 cm in two cases, and larger than 10 cm in 10 cases. Dense homogeneous
      contrast enhancement of the solid component was seen in 11 mixed masses. Ascites
      were found in all patients. Other evidence of peritoneal seeding and direct
      invasion into adjacent organ such as the uterus or sigmoid colon was seen in five
      patients each. Pleural metastasis was present in one patient. Surgical stages
      were FIGO classification IIIb and IV in one patient each, and IIIc in six
      patients. CONCLUSION: Ovarian MMMTs usually present as aggressive, bilateral,
      large, solid and cystic tumors, combined with ascites, frequent peritoneal
      seeding, and adjacent organ invasion.

PMID- 11471603
TI  - Twisted ovarian fibroma with high signal intensity on T1-weighted MR image: a new
      sign of torsion of ovarian tumors?
AB  - Torsion of ovarian tumors is often difficult to diagnose, because of non-specific
      clinical, laboratory, and imaging findings. We report a case of twisted ovarian
      fibroma whose main characteristic was the presence of large areas of high signal
      intensity on both T1- and T2-weighted MR images due to the passive congestion of
      the mass. This previously unreported finding should be considered a sign of
      ovarian torsion and may facilitate prompt surgical intervention.

PMID- 11471604
TI  - A prospective randomised study comparing enteroclysis with small bowel follow
      through examinations in 244 patients.
AB  - The purpose of this study was to determine whether small bowel enema or barium
      follow-through is the most appropriate examination for the routine investigation
      of patients without documented small bowel disease referred from outpatient
      sources in our hospital. Two hundred and forty-four patients were prospectively
      randomised to either small bowel enema (SBE) or barium follow-through (FT).
      Radiation doses and room times were recorded for the first 95 patients and
      abnormal results were documented for all. One hundred and twelve FTs and 75 SBEs
      were performed. The incidence of abnormal results was low overall and comparable
      in the two groups. There were significantly more abnormalities in the FT group
      which required further investigations for confirmation. Of those assigned to SBE,
      19% were converted to FT due to patient refusal and technical failure. Radiation
      doses were similar in the two groups, but the time spent occupying the
      fluoroscopy room was significantly shorter for FT. In our department FT is as
      effective as SBE in detecting small bowel abnormalities de novo. The radiation
      dose is similar, but more FTs can be performed per list. Follow-through is also
      less invasive than SBE and therefore we use this technique as the first line of
      investigation in this group of patients.

PMID- 11471605
TI  - The value of CT diagnosis of hernia recurrence after prosthetic repair of ventral
      incisional hernias.
AB  - Herein we present a prospective study made to compare the diagnostic value of a
      physical examination and a CT scan in the detection of a hernia relapse after
      carrying out of a intraperitoneal hernioplasty using a non-resorbable mesh. Fifty
      patients operated on for intraperitoneal hernioplasty with ePTFE mesh and
      postoperative symptomatology were assessed within a year of the operation via a
      physical exploration and CT. Each of the patients was subjected to an exploratory
      laparoscopy for the purpose of confirming the diagnosis. The data were analysed
      statistically using a chi-square test, sensitivity, specificity, confidence
      limits, positive predictive value, and negative predictive value. The hernia
      relapse was correctly diagnosed in 98% of cases by CT and in 88% of cases in the
      physical examination. The sensitivity was 1 in the CT examination and 0.75 in the
      physical examination, and the specificity results were 0.97 and 0.90,
      respectively. The positive predictive value in the CT exam was 0.88, whereas in
      the physical examination it was 0.60. The negative predictive values were 1 and
      0.95, respectively. The differences between the values of both methods held a
      statistical meaning (chi-square test; p < 0.05). The postoperative assessment by
      CT of symptomatic patients who have been operated on for an intraperitoneal
      hernioplasty with unabsorbable mesh facilitates carrying out a correct diagnosis
      in the detection or exclusion of hernial relapse.

PMID- 11471606
TI  - Comparison of transanal and external perineal ultrasonography.
AB  - Anal endosonography with rotating endoprobes provides state-of-the-art imaging of
      sphincter integrity; however, the technique is not widely available and requires
      expensive equipment. Since pelvic anatomy permits the use of standard external
      ultrasound probes, we tested the feasibility, tolerance and reproducibility of
      uniplanar perineal sonography, with respect to visualisation of the anal
      sphincter, using both convex and linear 3.5- to 7.5-MHz and 360 degree rotating 7
      MHz probes. Twenty healthy nulliparus female volunteers were investigated. Two
      operators performed endosonography and perineal sonography in duplicate, each
      blinded to the findings of the other. We then used this technique to examine 20
      postpartum primiparus patients. The examination was well tolerated by all
      subjects. The internal anal sphincter appeared in perineal sonography as a
      hypoechogenic ring surrounded by an echogenic ring representing the external anal
      sphincter. Endosonography revealed six sphincter tears, four external and
      internal sphincter tears, one isolated external tear and one isolated internal
      tear. Perineal sonography recognised in all cases external sphincter tears. In
      one case the internal sphincter defect was missed. Perineal sonography appears to
      be a feasible alternative to anal endosonography in female patients and provides
      good information on external sphincter defects suggesting that this procedure
      might be particularly useful in incontinence screening. Perineal sonography gives
      a good image of internal sphincter. The lack of an isolated internal defect
      cannot be considered as relevant to our study.

PMID- 11471607
TI  - Acute appendicitis in a young adult with midgut malrotation: a case report.
AB  - Midgut malrotation is defined as a developmental anomaly that may cause atypical
      clinical symptoms in relatively common intestinal disorders due to altered
      anatomy. A 27-year-old woman presented with acute left-sided abdominal pain.
      Underlying type Ia malrotation prevented the correct clinical diagnosis of
      perforated, ulcerated appendicitis. Cross-sectional imaging demonstrated all the
      typical signs of this type of malrotation, i.e., right-sided duodenojejunal
      junction, left positioned cecum and ascending colon, inverted position of the
      superior mesenteric vessels, and hypoplasia of the uncinate process of pancreas,
      and surgical treatment was initiated.

PMID- 11471608
TI  - Nonfunctioning endocrine tumors of the pancreas: possibilities of spiral CT
      characterization.
AB  - The aim of this study was to assess the ability of spiral CT to adequately
      characterize the nonfunctioning endocrine tumors (NFETs) of the pancreas,
      distinguishing this lesion from the other pancreatic tumors. The spiral CT
      examinations of 21 cases of histologically proven NFETs, along with those of 29
      cases of other pancreatic tumors and tumor-like lesions, were retrospectively
      reviewed in a blinded fashion by two radiologists, in order to correctly classify
      the lesions, highlighting the typical signs reported in the literature.
      Discordant cases were further analyzed in the presence of a third radiologist.
      The final diagnosis was acquired by means of a majority or overall consensus. The
      histopathologic examination was considered the gold standard. The sensitivity,
      specificity, and positive and negative predictive values of CT were calculated.
      After the consensus evaluation, the correct diagnosis was reached in 72% of
      cases, with 10% of nonspecific diagnoses of solid pancreatic tumor and 18% of
      wrong diagnoses. The sensitivity and specificity of spiral CT in identifying
      NFETs were 66.6 and 82.7%, respectively. The positive and negative predictive
      values were 73.7 and 77.4%, respectively. In up to 70% of cases the NFET
      demonstrates a typical aspect of a mass hyperdense in the arterial
      contrastographic phase eventually associated with hyperdense hepatic metastases
      in more than half of the patients. This finding does allow the diagnosis of NFET
      but without certainty indeed, since other tumors can show a similar densitometric
      behavior and among them particularly the ductal adenocarcinoma. On the other
      hand, both the solid, hypovascularized NFETs, and the cystic form, cannot be
      differentiated from the other solid and cystic tumors of the pancreas.

PMID- 11471609
TI  - Hepatosplenic antracosilicosis: a rare cause of splenic calcifications.
AB  - A case of a 62-year-old man with known longstanding pulmonary antracosilicosis,
      with associated hepatosplenic antracosilicosis, is presented. A CT scan of the
      upper abdomen revealed multiple calcifications within the spleen, and to a lesser
      degree within the subcapsular region of the liver, as well as "egg-shell"
      calcifications of abdominal lymph nodes, most noticeable at the splenic hilum.
      Although histopathologically not proven, the similar appearance of the calcified
      hepatosplenic nodules to the small round calcifications scattered throughout the
      lungs, as well as the typical "egg-shell" morphology of the calcified abdominal
      lymph nodes, should raise the suspicion of hepatosplenic antracosilicosis.

PMID- 11471610
TI  - Cystic lymphangioma of the spleen: US-CT-MRI correlation.
AB  - A case of a surgically confirmed cystic lymphangioma of the spleen is presented.
      Preoperative imaging consisted of US, contrast-enhanced CT and MRI, all showing a
      multiloculated lesion with small cystic cavities divided by thin septa,
      corresponding to dilated lymphatic spaces. Preoperative studies correlated well
      with the pathologic findings. Cystic lymphangioma of the spleen is a very rare
      condition and is usually solitary and asymptomatic. Large lymphangiomas may be an
      indication for splenectomy, since the risk of rupture is high even from minor
      abdominal trauma. Preoperative diagnosis may be achieved with correlated
      noninvasive imaging.

PMID- 11471611
TI  - Lymphatic mapping and retrieval of the sentinel lymph node in treatment of early
      breast cancer.
AB  - Lymphatic mapping and sentinel lymph node biopsy is an important step to surgical
      individualization of breast cancer therapy. With lymphatic mapping and minimally
      invasive biopsy of one or two detected lymph nodes the method provides an exact
      evaluation of the nodal status. Using sentinel lymph node biopsy (SLNB), costs
      and morbidity of an axillary lymph node dissection (ALND) can be avoided in nodal
      negative patients, whereas nodal positive patients are chosen for ALND very
      selectively according to the detection of an increased percentage of
      micrometastases. While experienced centers are introducing this method into
      clinical practice for the benefit of patients with early-stage breast cancer in
      Europe, further research should focus on quality control, definition of standards
      considering the individual needs of the individual patient, and the evaluation of
      the impact of micrometastases. This article gives an overview of the current
      knowledge of SLNB and discusses critically current indications and methods as
      well as application techniques.

PMID- 11471612
TI  - Calcified filariasis of the breast: report of four cases.
AB  - Circumscribed to endemic areas throughout tropical countries, filariasis is a
      rare and unknown disease in Europe. We report four cases of calcified filariasis
      involving the breast, supporting the diagnosis on the typical mammographic
      appearance of the calcified worms and the past history of filarial infection. Few
      reports have been published in the radiology literature about this infrequent
      manifestation of the parasitation. The purpose of this article is to show the
      mammographic characteristics of this disease that soon will be seen frequently in
      developed countries due to the increasing population from the endemic areas.

PMID- 11471613
TI  - Effect of contrast dilution on contrast-enhanced MR angiography of the aorta and
      renal arteries.
AB  - The aim of this study was to investigate the effect of gadolinium chelate
      dilution on vascular enhancement in contrast-enhanced two-dimensional (2D) MR
      subtraction angiography of aorta and renal arteries. Twenty patients were
      prospectively included. 2D subtraction MR angiography consisted of successive
      multisection breathhold GRE acquisitions of 16 s (2D FLASH, TR/TE 72/4, flip
      angle 60 degrees) obtained in the coronal plane before and after intravenous
      bolus administration of 0.1 mmol/kg BW gadolinium chelate. Patients underwent
      both diluted and undiluted gadolinium chelate administration in a random order.
      The data were studied both qualitatively and quantitatively on source and maximum
      intensity projection images. The length of renal arteries opacified was found not
      to differ significantly according to contrast dilution. The contrast enhancement
      percentage was not significantly modified according to the dilution used, but the
      time to peak enhancement was observed to be longer with the diluted contrast.
      Qualitatively, the best MR images were those obtained when undiluted contrast was
      injected first (chi2, P = 0.01). At a dosage of gadolinium chelate 0.1 mmol/kg
      BW, undiluted contrast 2D MR subtraction angiography seems to be more appropriate
      for studying diseases of the aorta and renal arteries than a similar diluted
      dose.

PMID- 11471614
TI  - Successful closure of large pseudoaneurysm of peroneal artery using transluminal
      temporary occlusion of the neck with the catheter.
AB  - Pseudoaneurysm is well-known complication resulting from surgical or
      interventional vascular procedures. We present the case of a 51-year-old patient
      with a large iatrogenic pseudoaneurysm of the peroneal artery, a very rare
      location. The pseudoaneurysm developed after orthopedic surgery of the knee.
      Swelling and vascular insufficiency of the calf ensued a few days later. The
      large peroneal pseudoaneurysm and compression of the anterior and posterior
      tibial arteries were confirmed by ultrasound and angiography. The pseudoaneurysm
      was too deep for ultrasound-guided compression or percutaneous obliteration and
      too large to be occluded by coil embolization alone. Because the pseudoaneurysm
      failed to occlude even after four coils were introduced into the lumen,
      pseudoaneurysm thrombosis was achieved by temporary occlusion of its neck with
      the angiographic catheter. During the occlusion of the neck of the
      pseudoaneurysm, the patency of the crural arteries and the development of the
      thrombus in the pseudoaneurysm cavity were monitored with color Doppler
      ultrasonography. Follow-up examinations after 3 and 6 months showed permanent
      closure of the pseudoaneurysm and patent crural arteries.

PMID- 11471615
TI  - CT and MRI of the semicircular canals in the normal and diseased temporal bone.
AB  - Imaging of the semicircular canals specifically is part of the imaging process of
      the temporal bone in general. The semicircular canals are easily seen on CT
      images and 3DFT-CISS-weighted MR images, both performed with 1.0-mm-thick slices,
      or even thinner slices. In selected cases, the T1-weighted images give unique
      information on the semicircular canals. This article briefly reviews the variety
      of semicircular canal anomalies that are most frequently present and can be
      routinely seen on CT and MR examinations of the temporal bone. It also provides a
      list that can be used by the radiologist in clinical practice to decide which
      technique, CT or MR, should be used to detect specific anomalies at the level of
      the semicircular canals.

PMID- 11471616
TI  - Quantitative assessment of regional cerebral blood flows by perfusion CT studies
      at low injection rates: a critical review of the underlying theoretical models.
AB  - Viability of the cerebral parenchyma is dependent on cerebral blood flow (CBF),
      which is usually kept in a very narrow range due to efficient autoregulation
      processes and can be altered in a variety of pathological conditions. An accurate
      method allowing for a quantitative assessment of regional cerebral blood flows
      (rCBF) and available for the routine clinical practice would, for sure, greatly
      contribute to improving the management of patients with cerebrovascular diseases.
      Different imaging techniques are now available to evaluate rCBF: positron
      emission tomography; single photon emission CT; stable-xenon CT; perfusion CT;
      and perfusion MRI. Each of these imaging techniques uses an indicator, with
      specific biological properties, and is supported by a model, which consists of a
      few simplifying assumptions, necessary to state and solve the equations giving
      access to rCBF. The obtained results are more or less reliable, depending on
      whether modeling hypotheses are fulfilled by the used indicator. The purpose of
      this article is to review the various supporting models in the assessment of
      rCBF, with special emphasis on perfusion CT studies at low injection rates and on
      iodinated contrast material used as an indicator.

PMID- 11471617
TI  - Comparison of dynamic contrast-enhanced MRI with WHO tumor grading for gliomas.
AB  - Assessment of vascular proliferation as an important grading criterion has been
      employed in both the histologic and the radiologic characterization of gliomas
      with encouraging results. Perfusion in gliomas can be measured by dynamic
      contrast-enhanced magnetic resonance imaging (dMRI). The goal of this study was
      to develop a model for simultaneously quantifying the fractional volumes of
      different tissue compartments of gliomas by dMRI. A modified method for
      evaluating dynamic contrast-enhanced MR images is presented which simultaneously
      determines the fractional vascular, interstitial, and cellular volumes of
      gliomas. This method differs from techniques used in other studies in that it is
      based on a three-compartment model: a single blood compartment and two
      interstitial ones. The fractional volume maps are compared with the WHO glioma
      grading. The results show the method to be feasible. Using cerebral blood volume
      (CBV), dMRI grading showed a correspondence with WHO grading in 83% of the cases
      (20/24 gliomas WHO grades II-IV). The use of interstitial volume maps can also be
      helpful, for instance, in differentiating gliomas from other brain tumors. As a
      supplement to conventional MRI, dynamic MR techniques thus provide a useful tool
      for improving in vivo glioma characterization.

PMID- 11471618
TI  - Cerebral aspergillosis: comparison of radiological and neuropathologic findings
      in patients with bone marrow transplantation.
AB  - Thirty-six lesions in six patients who died from cerebral Aspergillus infection
      after bone marrow transplantation (BMT) were studied with regard to signal
      intensity, contrast enhancement, size, and location. The diagnosis was confirmed
      in all cases by autopsy. Retrospective correlation of histopathological and
      radiological findings was possible for 14 lesions. Most of the lesions (22/36)
      had isointense to low signal intensity on T2-weighted images (T2WI).
      Histopathologically, hemorrhagic necrosis was determined in three of them. Areas
      of high signal intensity on T1-weighted images (T1WI) were related to gross
      hemorrhage. Two infarctions showed intravascular accumulation of fungal hyphae
      with secondary thrombosis of the vessel. The remaining 12 lesions had high signal
      intensity on T2WI and low on T1WI. Histopathologically, four were infectious and
      four were unspecific demyelinated lesions. In conclusion, cerebral aspergillosis
      typically presented with large lesions showing isointense to low signal intensity
      on T2WI that could have areas of high signal on T1WI. Contrast enhancement was
      only visible in 15 lesions, and the predominant locations were the subcortical
      white matter, the cerebellum, and the basal ganglia. Small lesions with high
      signal on T2WI and low signal on T1WI could not necessarily be related to
      Aspergillus infection.

PMID- 11471619
TI  - Intravascular stent placement for a fusiform aneurysm of the posterior cerebral
      artery: case report.
AB  - This article presents the case of a 45-year-old woman with a fusiform, broad
      based, actually ruptured aneurysm of the posterior cerebral artery. The patient
      was successfully treated with stent placement and follow-up angiography
      demonstrated occlusion of the dome and the body of the aneurysm. Due to the
      limited neurosurgical treatment options, stent placement should be considered in
      patients with fusiform aneurysm of the posterior cerebral artery aneurysms.

PMID- 11471620
TI  - Extensive spinal epidural hematoma: a rare complication of aortic coarctation.
AB  - Development of collateral circulation belongs among the typical signs of aortic
      coarctation. Cerebral or spinal artery aneurysm formation with increased risk of
      subarachnoid hemorrhage represent the most common neurovascular complication of
      this disease. We report a case of a 20-year-old sportsman who developed acute non
      traumatic paraplegia as a result of extensive spinal epidural hemorrhage from
      collateral vessels accompanying aortic coarctation which was unrecognized up to
      that time. To the best of our knowledge, acute spinal epidural hematoma as a
      complication of aortic coarctation has not been previously reported.

PMID- 11471621
TI  - Chronic granulomatous disease with gastric antral narrowing: a study and follow
      up by MRI.
AB  - We report the case of a boy with chronic septic granulomatosis (CSG) who
      presented with a marked gastric antrum narrowing which was evaluated by MRI after
      oral intake of magnetic contrast particles, and after gadolinium i.v.
      administration. In particular, a mammillated aspect of the gastric wall in the
      antral region was seen. Follow-up by MRI clearly showed the gradual resolution of
      hyperemic wall thickness, after medical management. The antral stenosis resolved
      after 3 months. Magnetic resonance imaging provides detailed evaluation of
      gastric wall inflammation in course of CSG.

PMID- 11471622
TI  - Intra-abdominal tuberculous peritonitis.
AB  - We report the case of a 15-year-old boy suffering from progressive dyspnea on
      exertion and painful abdominal protrusion. Final diagnosis of intra-abdominal
      tuberculosis (TB), including lymphadenopathy and abdominal abscess formation, was
      made following elective laparotomy. This type of disease is a rare manifestation
      of extrapulmonary tuberculosis. The imaging findings in unenhanced and contrast
      enhanced MRI and laparoscopic images are presented. Differential diagnosis of
      abdominal abscess formation and other fungal or bacteriological infections, as
      well as the imaging findings of this type of lesion, are discussed. This case
      demonstrates that atypical manifestation of TB may remain unrecognized; thus,
      awareness of this kind of manifestation of tuberculosis may prevent patients from
      being subjected to inappropriate therapies.

PMID- 11471623
TI  - Adverse reactions to iodinated contrast media.
AB  - Adverse reactions to iodinated contrast media (ICM) are more likely to develop in
      patients with asthma, a history of allergy or contrast reaction and in those who
      are debilitated or medically unstable. These reactions can be divided into renal
      and general, and the latter are subdivided into acute and delayed. Acute general
      reactions can be minor, intermediate or severe. Fatal reactions are rare. The
      introduction of low-osmolality agents has caused an overall reduction in the
      number of non-fatal contrast reactions. Prompt recognition and treatment of acute
      adverse side effects to ICM is invaluable and may prevent a reaction from
      becoming severe. Familiarity with cardiopulmonary resuscitation is essential for
      successful management of life-threatening reactions. Contrast-media-induced renal
      impairment can be reduced with the use of low-osmolality contrast media and
      extracellular volume expansion. The use of ICM in diabetic patients receiving
      metformin should be carried out with care to avoid metformin-induced lactic
      acidosis. However, this problem is mainly observed in patients with diabetic
      nephropathy.

PMID- 11471624
TI  - Carboxymethyldextran-A2-Gd-DOTA enhancement patterns in the abdomen and pelvis in
      an animal model.
AB  - The aim of this study was to assess MR signal enhancement patterns of
      carboxymethyldextran (CMD)-A2-Gd-DOTA, a new macromolecular contrast agent, in
      the abdomen and pelvis of New Zealand white rabbits. Nine New Zealand white
      rabbits underwent MRI before and following injection of 0.05 mmol/kg body weight
      (bw) CMD-A2-Gd-DOTA (52.1 kDa), using turbo FLASH-, dynamic FLASH 60 degrees-, T1
      and T2-weighted spin-echo and turbo spin-echo sequences up to 10 days p.i.
      Changes in blood and tissue signal intensities (deltaSI) and relaxation rates
      (deltaR1) were calculated. Differences between pre- and post-contrast MRI data
      were compared using the Scheffe test. CMD-A2-Gd-DOTA demonstrated significant
      blood-pool enhancement and significant tissue enhancement on T1-weighted images,
      whereas no significant signal changes were observed on T2-weighted images (P <
      0.05). Kidney parenchyma, pelvis and bladder demonstrated a subsequent
      enhancement, resembling renal elimination of the majority of the contrast agent.
      Liver parenchyma demonstrated a slow, delayed decay of the contrast enhancement
      due to storage and biodegradation of larger subfractions of the contrast agent.
      All tissue signal intensities were back to baseline 10 days p.i. CMD-A2-Gd-DOTA
      is a new macromolecular contrast agent with blood-pool effect, significant signal
      enhancement of abdominal organs and pelvic bone marrow, partial storage in the
      liver and baseline tissue signal intensities by 10 days p.i.

PMID- 11471625
TI  - Embolization of a ruptured aneurysm of the inferior thyroid artery.

PMID- 11471626
TI  - Quiz case of the month. Intramural hematoma in the caudal tract of the basilar
      artery with distal occlusion and a midsagittal ischemic lesion in the pons.

PMID- 11471627
TI  - Polygraph testing and sexual abuse: the lure of the magic lasso.
AB  - Polygraph tests to assess veracity are widely promoted for application in sexual
      abuse matters. The use of polygraph tests is advocated despite substantial
      differences in professional and scientific opinion about the validity of such
      techniques. Polygraph diagnoses of an individual's deception are inferences made
      by an examiner who compares physiological reactions to a set of questions. The
      test situation, however, is also used to induce examinees to admit crimes. In
      addition to their use in investigations, polygraph tests are used by defendants
      seeking exculpatory evidence and by treatment and probation programs to assess
      and monitor sexual offenders. Although there are dissenters, most knowledgeable
      scientists consider polygraph testing as unvalidated. Professionals need to
      access the literature on polygraph testing, evaluate the efficacy and ethics of
      polygraph tests in their community, and further develop standards for their use.

PMID- 11471628
TI  - Reducing recurrence in child protective services: impact of a targeted safety
      protocol.
AB  - Statewide implementation of a child safety assessment protocol by the Illinois
      Department of Children and Family Services (DCFS) in 1995 is assessed to
      determine its impact on near-term recurrence of child maltreatment. Literature on
      the use of risk and safety assessment as a decision-making tool supports the
      DCFS's approach. The literature on the use of recurrence as a summative measure
      for evaluation is described. Survival analysis is used with an administrative
      data set of 400,000 children reported to DCFS between October 1994 and November
      1997. An ex-post facto design tests the hypothesis that the use of the protocol
      cannot be ruled out as an explanation for the observed decline in recurrence
      following implementation. Several alternative hypotheses are tested: change in
      use of protective custody, other concurrent changes in state policy, and the
      concurrent experience of other states. The impact of the protocol to reduce
      recurrence was not ruled out.

PMID- 11471629
TI  - Factors in the underreporting of crimes against juveniles.
AB  - This analysis of 1995 to 1996 National Crime Victimization Survey (NCVS) data
      finds substantial underreporting to police of violent and property crimes against
      youth (age 12 to 17) compared with the reporting of such crimes against adults.
      This underreporting is not explained by the crimes involved being less serious,
      being committed by juvenile perpetrators, or by any other aspect of the crimes
      for which NCVS information is available. Counting reports to nonpolice
      authorities (in lieu of police) equalizes the level of reporting for property
      crime but not for violent crime. Law enforcement should undertake a variety of
      policies to try to encourage the police reporting of juvenile crime
      victimization, including steps to emphasize the criminal seriousness of such
      offenses, to undermine the code of silence, to provide incentives to report, to
      make reporting easier, and to work with schools about policies concerning when to
      involve the police.

PMID- 11471630
TI  - Extended forensic evaluation when sexual abuse is suspected: a multisite field
      study.
AB  - A subset of children referred due to suspected sexual abuse require more than one
      interview for professionals to reach an opinion about the veracity of
      allegations. The National Children's Advocacy Center's forensic evaluation model
      was designed for that specific group of children. The multisite study of the
      model reported here followed a 2-year pilot study. Professionals in 12 states
      adopted the model and collected data for 2 years on a total of 147 participants.
      In 44.5% of the cases, a credible disclosure was obtained, with 73% of these
      cases supported in the legal system. The forensic evaluation procedure yielded
      clear information to be used in child protection and prosecutory decisions in 64%
      of the cases (combining cases with credible disclosures and abuse unlikely
      findings). Finally, the study examined the effects of the length of the
      evaluation and of the case and child characteristics on evaluation outcomes.

PMID- 11471631
TI  - The youngest victims of child maltreatment: what happens to infants in a court
      sample?
AB  - Current data show that infants represent an increasing proportion of cases of
      child maltreatment. To learn more about how infants fare in the current system
      and to provide baseline data against which to compare outcomes following recent
      legislative reforms, this study examined a subsample of infants in a sample of
      200 care and protection cases brought before the Boston Juvenile Court in 1994.
      Child, parent, and case characteristics of infants 0 to 3 months of age (n = 46)
      were compared with characteristics of older children in the sample. All cases
      were followed prospectively for 4 years, and data were abstracted from court
      records. Results revealed that the infants were primarily children of substance
      abusers who had extensive prior histories of child protective service system
      involvement. Although the majority of the infants were eventually permanently
      removed from parental custody and adopted, many experienced time delays and
      multiple placements before achieving permanent homes.

PMID- 11471632
TI  - Predictors of medical examinations following child and adolescent rapes in a
      national sample of women.
AB  - Childhood rape occurs frequently in our society and is associated with adverse
      consequences. Despite the severity of these outcomes, there appear to be many
      obstacles for children to receive postrape medical care. To date, it is unclear
      what proportion of childhood rape victims receive postrape medical examination or
      what factors predict receipt of this medical care. This study instigated the
      factors predicting immediate medica care for women who were raped during
      childhood. Data for the study were obtained from the final wave of the 2-year,
      longitudinal National Women's Study. Results indicated that the majority of women
      did not receive medical care following their childhood rape. Although women raped
      as adolescents were more likely to receive a postrape exam, logistic regression
      analyses indicated that rape characteristics (e.g., reporting the assault,
      concerns about sexually transmitted diseases [STDs]) mediated the relationship
      between age of victimization and receipt of medical care. Implications of these
      findings are discussed.

PMID- 11471633
TI  - The Social Behavior Inventory for children in a child abuse treatment program:
      development of a tool to measure interpersonal behavior.
AB  - This article presents information about a tool that can be completed in a few
      minutes to measure the interpersonal behavior of childen particpating in a child
      abuse treatment program. One sample of children came from the community and had
      no reported history of abuse or mental health services. A second sample was
      children obtaining therapy services through a child abuse treatment program.
      Factor analysis of scores provided by parents for their children obtaining
      therapy services led to the development of three scales to assess aversive
      interpersonal behavior, two to measure prosocial interpersonal behavior, and one
      to measure total interpersonal competence. Numerous indices of liability and
      validity are presented. Data delineated the potential value of the scales for
      assessing the impact of therapy. The current results suggested that the Social
      Behavior Inventory may have value as a measure of interpersonal behavior when
      providing therapy to children in a child abuse treatment program if used
      prudently.

PMID- 11471634
TI  - Case 10.

PMID- 11471635
TI  - Occurrence of Candida albicans in infections of endodontic origin.
AB  - Microorganisms are recognized as the etiological agent for the majority of pulpal
      and periradicular disease. Although bacteria have been the most studied, fungi
      have also been associated with infected root canals. The purpose of this study
      was to evaluate the contents of infected root canals and aspirates of
      cellulitis/abscesses of endodontic origin for the presence of Candida albicans
      using the polymerase chain reaction (PCR). PCR primers specific for the 18S
      ribosomal RNA gene of C. albicans were used to survey 24 samples taken from
      infected root canals and 19 aspirates from periradicular infections of endodontic
      origins. The presence of C. albicans was detected in 5 of 24 (21%) samples taken
      from root canals, but none was detected in the periradicular aspirates. The
      results indicate that PCR is an extremely sensitive molecular method that may be
      used to identify C. albicans directly in samples from infections of endodontic
      origin.

PMID- 11471636
TI  - Determination of periodontal ligament cell viability in long shelf-life milk.
AB  - The purpose of this study was to determine the ability of long shelf-life milk to
      serve as a temporary storage medium for the maintenance of periodontal ligament
      (PDL) cell viability on avulsed teeth. PDL cells were plated onto 24-well culture
      plates and allowed to attach for 24 h. Minimal Essential Medium was replaced with
      regular pasteurized milk (refrigerated milk), long shelf-life milk (Parmalat), or
      Save-A-Tooth. Tap water served as the negative control, and Minimal Essential
      Medium served as the positive control. The tissue culture plates were incubated
      at 37 degrees C for 1, 2, 4, or 8 h. Cell viability was determined using a cell
      proliferation assay (CellTiter 96 AQ Assay) and absorbance read at 490 nm. ANOVA
      indicated that all media performed significantly better than tap water at all
      time periods. At 8 h, PDL cell viability in regular pasteurized milk and long
      shelf-life milk were significantly greater than in Save-A-Tooth (p < or = 0.001).
      There was no significant difference between regular pasteurized milk and long
      shelf-life milk at any time period. These results suggest that long shelf-life
      milk, which has the advantage of not requiring refrigeration, is as effective a
      storage medium for avulsed teeth as regular pasteurized milk and more effective
      than Save-A-Tooth.

PMID- 11471637
TI  - Cytotoxicity of root canal filling materials to three different human cell lines.
AB  - The aim of this study was to investigate the biological compatibility of five
      root canal sealers (Sealapex, Endion, Super-EBA, Ketac-Endo, and AH Plus) and
      regular and calcium hydroxide-based gutta-percha in three different human cell
      lines. Cultures without root canal sealers were used as controls. Cell growth,
      cell morphology, cell viability, protein content of the cells, and prostaglandin
      E2 (PGE2) release were used as parameters to determine the cytotoxicity of the
      materials. The protein content of the three cell lines--nasal fibroblasts,
      gingival fibroblasts, and epithelial tumor cells--was significantly reduced (p <
      or = 0.001) by all materials tested. Determinations of PGE2 release showed
      significant material specific differences. No significant increased PGE2 release
      values were found with Sealapex, Endion, and Super-EBA. On the contrary
      significantly increased PGE2 levels were measured with Ketac Endo, AH Plus,
      regular and calcium hydroxide-based gutta-percha points (p < or = 0.001).

PMID- 11471638
TI  - Immunohistochemical localization of tenascin, fibronectin, and type III collagen
      in human dental pulp.
AB  - The distribution of tenascin (TN), fibronectin (FN), and type III collagen (col
      III) in the extracellular matrix of the connective tissue of normal, inflamed,
      and hyalinized human dental pulp was studied by immunohistochemical staining with
      monoclonal antibodies against these molecules. TN, FN, and col III were present
      in all normal tissues studied. In areas of hyalinization only col III was
      observed. None of the molecules studied were seen in areas of inflammatory
      exudate. Strong staining for TN and FN was found in the periphery of all
      specimens analyzed next to the odontoblastic layer. We therefore conclude that
      TN, FN, and col III are present in the extracellular matrix of normal human
      dental pulp. TN, FN, and col III distribution in inflammatory and degenerative
      processes is different from that observed in normal human dental pulp.

PMID- 11471639
TI  - The effectiveness of prophylactic etodolac on postendodontic pain.
AB  - To determine if prophylactic etodolac would significantly reduce postendodontic
      pain, when compared with ibuprofen or placebo, 36 patients consented to single
      blind oral administration of either 400 mg of etodolac, 600 mg of ibuprofen, or a
      placebo, before conventional one-appointment root canal therapy. Patient-reported
      visual analog scale ratings of pain intensity were conducted upon initial
      clinical presentation, immediately postoperative, 4, 8, 12, 24, 48, and 72 h
      after initiation of root canal therapy. Results showed that prophylactic
      ibuprofen administration significantly reduced postendodontic pain at 4 and 8 h
      after initiation of root canal therapy, when compared with etodolac and a
      placebo. Patients with a periapical diagnosis of acute apical periodontitis or
      with a Phoenix abscess showed a significant increased need for additional
      medication after completion of root canal therapy, compared with all other
      periapical diagnoses.

PMID- 11471640
TI  - The walking bleach procedure: an in vitro study to measure microleakage of five
      temporary sealing agents.
AB  - The purpose of this study was to compare the in vitro sealing capacity of five
      materials, each used as a temporary sealing agent for the walking bleach
      technique. All teeth received traditional biomechanical root canal
      instrumentation, after which the walking bleach agent was placed in the pulp
      chamber space. The occlusal access was sealed with one of five temporary
      materials: two hydraulic filling materials, a photoactivated resin composite, a
      zinc oxide-eugenol cement, and a zinc oxide phosphate cement with/without the
      placement of a piece of rubber sheet that was placed as a barrier to isolate
      filling material from the bleaching agent. All teeth were stored in a 1% solution
      of Alcian blue with thermal cycling stress. After 1 wk, they were sectioned
      longitudinally, and ranked by graded scores of 0 to 3, according to the degree of
      the dye penetration. Significantly less dye microleakage was observed in the two
      hydraulic materials than in the photoactivated resin. Both zinc oxide-eugenol and
      zinc phosphate cements showed a considerable amount of microleakage. There were
      no significant differences between the groups with and without a rubber sheet.
      Our data demonstrate that hydraulic filling materials provide the most favorable
      cavosurface seal when they are firmly packed into the cavity space to prevent
      microleakage.

PMID- 11471641
TI  - Shaping ability of three ProFile rotary instrumentation techniques in simulated
      resin root canals.
AB  - The aim of this study was to compare the shaping ability of three ProFile rotary
      instrumentation techniques and a conventional step-back method in simulated root
      canals. Prevalence of canal aberrations, change in working length, and
      preparation time were measured. A total of 48 composite images were made from pre
      and postcanal scanned images using Corel Photopaint 8.0 and then the amount of
      coronal substance the instruments removed was also calculated two-dimensionally
      on digitized images with the Brain C software to compare the enlarging
      efficiency. There were no significant differences between the three rotary groups
      in preparation time, change in working length, and the incidence of aberrations
      (p > 0.05). The amount of coronal substance the instruments removed in the
      ProFile .04 taper group was significantly smaller than the other three groups (p
      < 0.05).

PMID- 11471642
TI  - Correlation between remaining length of root canal fillings after immediate post
      space preparation and coronal leakage.
AB  - The seal provided by root canal fillings after post space preparation was studied
      using a pressure-driven radioactive tracer assay. The coronal part of root canal
      fillings was immediately removed, using a hot plugger, to a remaining length of
      either 3, 5, 7, or 9 mm. Intact root canal fillings of 14 mm served as control.
      Application of air pressure of 130 mm Hg to the tracer solution drove it through
      the fillings and into phosphate-buffered saline surrounding the apex. Leakage
      gradually increased for 28 days, and differences in the leakage through 3 to 9 mm
      fillings were demonstrated. In a passive system by which an additional group of
      teeth were tested none of these differences could be detected. It was concluded
      that: (a) root canal fillings of 3, 5, and 7 mm have an inferior seal, compared
      with that of an intact filling; (b) the sealing is proportional to the length of
      the remaining filling; and (c) a passive system is unable to detect these
      differences, even when conducted for as long as 28 days.

PMID- 11471643
TI  - Detection of Porphyromonas endodontalis in infected root canals by 16S rRNA gene
      directed polymerase chain reaction.
AB  - Porphyromonas endodontalis has been isolated from the endodontic infections
      mainly in symptomatic teeth. This study evaluated the occurrence of P.
      endodontalis in both symptomatic and asymptomatic endodontic infections using 16S
      rRNA gene-directed polymerase chain reaction. P. endodontalis was detected in
      39.5% of the cases (17 of 43 teeth). It was present in 4 of the 6 cases with
      acute periradicular abscess (66.7%) and in 13 of the 37 other cases (35.1%). The
      presence of P. endodontalis was associated with an asymptomatic periradicular
      lesion in 6 cases (25%) and in 10 teeth with tenderness to percussion (52.6%). P.
      endodontalis was also found in one asymptomatic case without evidence of
      periradicular pathosis. Our results indicated that, although P. endodontalis is
      commonly detected in symptomatic cases, it can be present in asymptomatic root
      canal infections. Further studies should determine if this bacterial species is
      really an important endodontopathogen.

PMID- 11471644
TI  - Comparison of laterally condensed and low-temperature thermoplasticized gutta
      percha root fillings.
AB  - The aim of this study was to evaluate and compare the radiographic quality and
      sealability of root fillings in extracted human teeth using lateral condensation
      of gutta-percha or low-temperature thermoplasticized gutta-percha (Ultrafil). One
      hundred freshly extracted human, mature single-rooted teeth were divided into
      four identical groups of 25 teeth on the basis of root canal shape. The root
      canals of two groups were prepared in such a way to produce a relatively parallel
      shape with little or no flare toward the coronal orifice. The root canals of the
      other two groups were prepared in such a way as to produce a canal shape that was
      deliberately more flared to ensure that they were wider at the orifice than at
      the end point of the preparation. All root canals were flushed with 17% EDTA
      solution and 2.5% NaOCl to remove the dentinal smear layer. The canals of one
      flared group and one parallel group were obturated using cold lateral
      condensation, and the canals of the other two groups were obturated using low
      temperature thermoplasticized gutta-percha. The sealability of each technique was
      assessed by a dye penetration method. The radiographic quality of obturation was
      determined for each canal using a 4-point scale. Canals filled with
      thermoplasticized gutta-percha had significantly less apical dye penetration than
      those obturated by lateral condensation (p < 0.001). Lateral condensation
      achieved significantly better scores for radiographic quality than
      thermoplasticized gutta-percha from both the buccolingual (p < 0.005) and
      mesiodistal views (p < 0.001). Low-temperature thermoplasticized gutta-percha
      root fillings were associated with significantly more apical extrusion of sealer
      (p < 0.001) and gutta-percha (p < 0.005). Under laboratory conditions the low
      temperature thermoplasticized gutta-percha had better sealability but poorer
      radiographic quality than lateral condensation.

PMID- 11471645
TI  - A comparative study of smear layer removal using different salts of EDTA.
AB  - Three solutions of EDTA--a 15% concentration of the alkaline salt, a 15%
      concentration of the acid salt, and a 25% concentration of the alkaline salt-
      were evaluated for smear layer removal in root canal systems. All solutions were
      adjusted to pH 7.1 using either NaOH or HCl. When the EDTA solutions were
      alternately used for root canal irrigation with 5.25% NaOCl, they completely
      removed the smear layer in the middle and coronal thirds of canal preparations,
      but were less effective in the apical third. None of the EDTA solutions by
      themselves were effective at completely removing the smear layer at any level.
      The alkaline tetrasodium salt, pH adjusted with HCl, is more cost effective and
      performed equally as well as the more commonly used disodium salt.

PMID- 11471646
TI  - Bradykinin levels in dental pulp by microdialysis.
AB  - Bradykinin is a potent mediator of pain and inflammation. To examine
      extracellular levels of bradykinin in human dental pulp, CMA/20 microdialysis
      probes were inserted into the pulp tissue of 22 teeth diagnosed with normal pulp
      or with irreversible pulpitis before their extraction or endodontic therapy.
      Probes were perfused with a modified Locke-Ringer's buffer and bradykinin levels
      in the dialysate evaluated using a radioimmunoassay. Mean extracellular levels of
      bradykinin within pulp tissue diagnosed with irreversible pulpitis were
      significantly higher (262.26 +/- 83.79 fmol/ml) than that found within normal
      pulp (19.41 +/- 6.47 fmol/ml). Highest levels of bradykinin were detected in pulp
      tissue diagnosed with irreversible pulpitis when the patient had reported pain in
      the past, compared with patients who were in pain just before their visit. These
      observations suggest that the bradykinin system is activated during pulpitis and
      may contribute to pain and inflammation.

PMID- 11471647
TI  - Increased density of gutta-percha using a controlled heat instrument with lateral
      condensation.
AB  - The purpose of this study was to compare quantitatively the density of standard
      cold lateral gutta-percha condensation and warm lateral gutta-percha condensation
      using the System B heating instrument in a low-heat warm lateral condensation
      technique in an artificial root canal in vitro. Thirty-degree simulated root
      canals in 30 transparent acrylic blocks were instrumented using Gates-Glidden
      burs and Quantec (NT Company, Chattanooga, TN) rotary files. The canals were then
      obturated with gutta-percha using standard cold lateral condensation without
      sealer. Warm lateral condensation without sealer using the System B instrument at
      101 degrees C was then performed on the same 30 canals. A second treatment of
      warm lateral condensation was then applied to these same canals. The blocks were
      weighed after the initial canal preparation and after each obturation treatment.
      Results showed warm lateral condensation of gutta-percha using the System B
      resulted in a significant increase in density by weight when compared with
      standard cold lateral condensation. A 23.97% increase in weight was realized
      after the first heat application, compared with standard lateral condensation. A
      second heat application produced an additional 2.59% increase in weight over that
      produced by the first heat application. Data were analyzed using a t test for
      repeated measures. Both increases were statistically significant (p < 0.001).
      Warm lateral condensation using the System B instrument results in denser gutta
      percha fills by weight when compared with standard cold lateral condensation.

PMID- 11471648
TI  - Reduction of intracanal bacteria using nickel-titanium rotary instrumentation and
      various medications.
AB  - The purpose of this study was to evaluate the extent of bacterial reduction with
      nickel-titanium rotary instrumentation and 1.25% NaOCl irrigation. Also, the
      additional antibacterial effect of calcium hydroxide for >1 wk was tested. Forty
      two subjects with radiographic and clinical signs of chronic apical periodontitis
      were recruited. The canals were sampled before treatment, during and after
      instrumentation, and after treatment with calcium hydroxide and the samples
      incubated anaerobically for 7 days at 37 degrees C. The bacteria from each sample
      were quantified and the log10 values were used for calculations and comparisons.
      The initial sample confirmed infection of the canals. There was a significantly
      greater pattern of reduction of bacteria when NaOCl was used as an irrigant,
      compared with sterile saline (p < 0.05). After instrumentation with NaOCl
      irrigation, 61.9% of canals were rendered bacteria-free. The placement of calcium
      hydroxide for at least 1 wk rendered 92.5% of the canals bacteria free. This was
      a significant reduction, compared with NaOCl irrigation alone (p = 0.0001). The
      results of this study indicate that NaOCl irrigation with rotary instrumentation
      is an important step in the reduction of canal bacteria during endodontic
      treatment. However this method could not consistently render canals bacteria
      free. The addition of calcium hydroxide intracanal medication should be used to
      more predictably attain this goal.

PMID- 11471649
TI  - A description of an alternative method of lateral condensation and a comparison
      of the ability to obturate canals using mechanical or traditional lateral
      condensation.
AB  - A modification of the lateral condensation of gutta-percha technique is
      described. After master cone adaptation is completed a nickel-titanium finger
      spreader placed in a reciprocating-action handpiece is used to laterally displace
      cold gutta-percha, creating space for accessory cones. The technique produces a
      compacted mass of gutta-percha in the canal, which can usually be removed in toto
      if corrections are required. This technique was compared with lateral
      condensation by obturating curved or straight canals in acrylic blocks, then
      removing, sectioning, and weighing the gutta-percha mass. Two different operators
      were also compared. Results were analyzed using a factorial ANOVA test. The
      experimental obturations were significantly heavier on average than were lateral
      condensation fills (p < 0.001). One operator's obturations were consistently
      heavier than the others (p < 0.001). There was no significant difference between
      the weight of fills in straight and curved canals.

PMID- 11471650
TI  - Central (intraosseous) adenoid cystic carcinoma of the mandible: report of a case
      with periapical involvement.
AB  - Primary intraosseous salivary gland tumors are rare, with mucopidermoid carcinoma
      being the most frequent histotype. The authors present a case of adenoid cystic
      carcinoma, located in the mandibular incisor region, associated with pain.
      Endodontic treatment resulted in increased pain and progressive mandibular
      expansion. An apicoectomy was conducted, and an intraosseous adenoid cystic
      carcinoma was diagnosed at histological examination. The patient was treated by
      wide surgical resection, and is alive and well without recurrences or distant
      metastases 14 yr after the original diagnosis. The case presented herein calls
      attention to the preoperative clinical diagnosis of periapical lesions.
      Radiologically, focal sclerosing osteitis, cementoblastoma, cementifying and
      ossifying fibroma, periapical cemental dysplasia, complex odontoma, and
      calcifying epithelial odontogenic tumor should be considered in the differential
      diagnosis. In addition the unusual occurrence of salivary gland tumors in
      intraosseous location stresses the importance of systematic histological
      examination of any tissue sample obtained after endodontic procedures.

PMID- 11471651
TI  - A new mineral trioxide aggregate root-end filling technique.
AB  - Carrier and syringe-type devices are currently used to deliver mineral trioxide
      aggregate as a root-end filling material. In certain surgical situations these
      devices may be too difficult to use because of the location of the surgical site
      and the small size of the root-end preparation. This paper describes a new
      technique to overcome these difficulties by the formation and delivery of mineral
      trioxide aggregate pellets.

PMID- 11471652
TI  - Global warming--a good thing for endodontics!

PMID- 11471653
TI  - Contribution of cardiac muscle cell disorganization to the clinical features of
      hypertrophic cardiomyopathy.
AB  - Heart failure rarely develops in the setting of hypertrophic cardiomyopathy
      (HCM). Because of this, cardiac muscle cell disorganization (CD), which is a
      histologic characteristic of HCM, is not believed to be responsible for the
      development of systolic dysfunction. The aim of the present study was to clarify
      whether CD can cause systolic dysfunction and ventricular dilation in patients
      with HCM. Sixteen hearts from patients with HCM obtained at autopsy were divided
      into two groups: group A (n = 11), without biventricular dilation, and group B (n
      = 5), with dilation. Specimens consisting of transverse and longitudinal tissue
      sections of the ventricles were prepared, and the extent of CD and interstitial
      fibrosis was quantified, using light microscopy. None of the patients in group A
      had had chronic congestive heart failure, while all of the patients in group B
      had died of congestive heart failure. In group B, CD was not limited to the
      interventricular septum. Rather, diffuse CD was observed in both ventricular free
      walls. The extent of CD was significantly greater in group B than in group A,
      while the degree of interstitial fibrosis was similar in the two groups (13.6% in
      group A vs 14.6% in group B). These results suggest that CD may be responsible
      for systolic dysfunction and ventricular dilation.

PMID- 11471654
TI  - Quantitative evaluation of coronary stenosis by coronary magnetic resonance
      angiography.
AB  - Coronary magnetic resonance angiography (coronary MRA) can detect, noninvasively,
      a high proportion of severe stenotic lesions found on coronary angiograms.
      However, quantitative evaluation of coronary artery stenosis by coronary MRA has
      been performed only in a small number of patients. This study was designed to
      determine whether coronary MRA can assess the degree of stenosis using the two
      dimensional segmented turbo-FLASH method (2D method). We studied 108 patients
      with technically adequate coronary MRA images. The blood flow signal intensity on
      coronary MRA was classified as markedly decreased, moderately decreased, or
      normal. The severity of coronary artery stenosis was determined by the caliper
      method, and coronary stenosis was rated using a seven-point scale (0%, 25%, 50%,
      75%, 90%, 99%, and 100%) in accordance with the American Heart Association
      classification system. Patients were classified into three groups: normal
      coronary artery (0%-25% stenosis), moderate stenosis (50%-75% stenosis), and
      severe stenosis (90%-100% stenosis). The degree of stenosis on coronary
      angiography and the decrease in coronary MRA signal intensity were compared. The
      right coronary artery was evaluated in 64 patients and the left coronary artery
      in 73 patients. When a marked or moderate decrease in coronary MRA blood flow
      signal intensity was defined as indicating stenosis, the sensitivity and
      specificity of coronary MRA for detecting angiographically severe stenosis were
      85% and 80%, respectively. A moderate decrease in coronary MRA blood flow signal
      intensity detected angiographically moderate stenoses with a sensitivity of 38%
      and a specificity of 83%. Coronary MRA can detect a high proportion of severe
      stenoses but only a low proportion of moderate stenoses. Technical improvements
      are required before coronary MRA can be used clinically.

PMID- 11471655
TI  - Determinants and prognostic value of ischemic necrosis in early biopsies
      following heart transplant.
AB  - To evaluate the impact of early ischemic necrosis (IN) on the early and late
      outcome of heart transplantation, we reviewed our 11-year experience. Between
      January 1988 and June 1999, 207 heart transplants were performed in 205 patients
      (174 male and 31 female). Criteria for donor and recipient selection, and
      protocols for postoperative immunosuppression and rejection monitoring have
      remained unchanged over this period. Three different cardioplegic solutions were
      employed in graft preservation: St. Thomas Hospital solution in the earliest 31
      cases (15%), University of Wisconsin solution in 96 cases (46.4%), and Celsior
      solution in the last 80 cases (38.6%). All patients who underwent at least one
      endomyocardial biopsy (176 patients) were divided into two groups according to
      the findings of IN within the early 3 postoperative months (group A, 49 patients
      with IN; group B, 127 patients without IN). The following variables were
      estimated in each group: donor and recipient age, ischemic time, type of
      cardioplegia, late mortality for cardiac causes, incidence of grade >2 rejection
      within the first 6 postoperative months, late incidence of grade >2 rejection,
      late incidence of NYHA class >II. No significant difference was found in any
      parameter between the two groups, except for the type of cardioplegic solution. A
      significantly higher incidence of ischemic necrosis in hearts preserved with St.
      Thomas solution was found (P < 0.001). Although pathology findings show that
      extracellular solutions carried a higher risk of early IN, no associated
      significant impairment in terms of late survival and event-free rate was observed
      in recipients with early IN.

PMID- 11471656
TI  - Point mutations in mitochondrial DNA of patients with alcoholic cardiomyopathy.
AB  - The pathogenesis of alcoholic cardiomyopathy (ACM) is not well understood.
      However, recent reports have shown that mutations in mitochondrial DNA (mtDNA)
      were associated with mitochondrial encephalomyopathy and cardiomyopathy. Our
      objective was to explore point mutations in mtDNA and the pathogenesis of ACM. We
      obtained heart biopsy specimens from ten male habitual drinkers with congestive
      heart failure. We amplified the total mtDNA obtained from these specimens using a
      two-step polymerase chain reaction method and analyzed the products using
      automated fluorescence-based direct sequencing. The sequences were compared with
      those of controls. MtDNA from the ACM patients contained multiple point
      mutations. Specifically, four of the ten patients carried five point mutations
      that had been detected previously in several other mitochondrial diseases. These
      point mutations were not observed in controls. These results suggest that mtDNA
      abnormalities are involved in the pathogenesis of ACM.

PMID- 11471657
TI  - Age-dependent impairment of coronary collateral development in humans.
AB  - The purpose of this study was to evaluate whether age influences collateral
      development in patients with coronary artery disease. The extent of collateral
      development to the area perfused by the infarct-related artery was graded,
      depending on the degree of opacification of the occluded infarct-related artery.
      We evaluated the extent of collateral development using coronary cineangiography
      in 102 patients with an acutely occluded infarct-related coronary artery within
      12 h after the onset of the first acute myocardial infarction, and who had a
      history of long-standing effort angina. Well-developed collateral circulation was
      observed in 54 (53%) of the patients. The patients were divided into two groups
      based on their age. The prevalence of well-developed collateral circulation in
      the younger group (< or = 64 years, n = 48) was 69% (33 of 48), being
      significantly (P = 0.003) higher than 39% (21 of 54) in the older group (> or =
      65 years, n = 54). We conclude that in the presence of stimuli for collateral
      development i.e., long-standing effort angina accompanied by severe coronary
      stenosis, the age of patients is a key determinant of collateral development.

PMID- 11471658
TI  - Physiological or pseudophysiological ECG changes in endurance-trained athletes.
AB  - "Sudden cardiac death" in seemingly healthy, active, and asymptomatic people has
      always been a tragic fact and is now occurring more frequently. Thus, the
      preventive detection of "subjects at risk" becomes a priority. A traditional
      resting electrocardiogram can sometimes give useful indications. Fifty-two
      competitive triathletes were compared with 22 control persons with similar
      anthropometric parameters. All subjects underwent the same noninvasive cardiac
      exploration with electrocardiography, bidimensional echo-Doppler examination, and
      maximal spiroergometric exercise tests, on a stationary bicycle as well as on a
      treadmill. In the triathletes we noted manifest signs of eccentric as well as
      concentric left ventricular hypertrophy with arguments for a supernormal
      diastolic left ventricular function, with important hemodynamic adjustments and
      with consequences on the resting electrocardiogram. We described "ten
      commandments" in evaluating the resting electrocardiogram of healthy competitive
      athletes. We suspect that the occurrence of ventricular premature beats at peak
      load of a maximal exercise could be the first expression of a pathological
      cardiac adaptation to sports activities. The resting electrocardiogram can show
      interesting details in detecting the "subjects at risk" for problems such as
      possible lethal arrhythmias and "sudden cardiac death." The analysis of the four
      subgroups of triathletes compels us to feel dubious about the "athletic heart
      syndrome" as a physiological entity. In several cases the "athletic heart" is
      possibly a transitional situation to a pathological hypertrophic and dilated
      cardiomyopathy.

PMID- 11471659
TI  - A nuclear complex containing PPARalpha/RXRalpha is markedly downregulated in the
      hypertrophied rat left ventricular myocardium with normal systolic function.
AB  - The expression of genes encoding fatty acid utilization enzymes is coordinately
      downregulated during the development of cardiac hypertrophy and failure. However,
      molecular mechanisms that mediate this downregulation are unknown. Peroxisome
      proliferator-activated receptor (PPAR) response elements (PPREs) have been
      identified in promoters of many genes involved in fatty acid utilization, where
      they function as positive regulatory elements. PPARs bind to PPREs as
      heterodimers with retinoid X receptors (RXRs). Primary cardiac myocytes from
      neonatal rats were transfected with a reporter construct driven by the C promoter
      of rat acyl-coenzyme A synthetase (ACS) gene. Stimulation with phenylephrine, a
      potent inducer of hypertrophy, markedly downregulated the activity of this
      promoter. By use of electrophoretic mobility-shift assays (EMSAs) using PPRE in
      the rat ACS promoter as a probe, we found a sequence-specific protein-DNA complex
      in the nuclear extract from adult rat left ventricular (LV) myocardium.
      Supershift experiments revealed that this complex was immunoreactive for
      PPARalpha and RXRalpha. We compared the activity of this complex in LV nuclear
      extracts from Dahl salt-sensitive rats (DSs) with hypertension and control age
      matched Dahl salt-resistant rats (DRs). Even at the stage of concentric LV
      hypertrophy with normal systolic function, the activity of the band was markedly
      diminished in DSs compared with DRs. However, immunoblot analyses showed no
      difference in LV expression levels of PPARalpha or RXRalpha between DSs and DRs.
      These findings indicate that a nuclear complex of PPARalpha/RXRalpha is present
      in adult rat LV and is markedly downregulated in the hypertrophied LV from DS
      rats, which may account for the loss of transcriptional activation. The
      downregulation of this complex precedes LV systolic dysfunction and is mediated
      at the posttranslational levels.

PMID- 11471660
TI  - Age-related decline of PCr/ATP-ratio in progressively hypertrophied hearts of
      spontaneously hypertensive rats.
AB  - Although the ultimate cause for the myocardial dysfunction of hypertensive heart
      disease is still unclear, a crucial role of the myocardial energy metabolism has
      been suggested. Therefore, the aim of the present study was to investigate
      whether age-related myocardial dysfunction in hearts of spontaneously
      hypertensive rats (SHR) is associated with an impaired myocardial energy
      metabolism. Isolated hearts of SHR and Wistar Kyoto rats (WKY) aged about 40, 60,
      and 80 weeks, respectively (each n = 4-5), were perfused according to the working
      heart technique. Cardiac work and coronary flow were monitored online. Myocardial
      energy metabolism was evaluated by calculating the ratio of phosphocreatine (PCr)
      and adenosine triphosphate (ATP) which were measured by nuclear magnetic
      resonance (31P-NMR) spectroscopy. All hearts were subjected to work for 30min at
      baseline conditions (low afterload), followed by another 30min under a moderate
      pressure load (high afterload). Each SHR group showed a higher heart weight/body
      weight ratio than the age-matched WKY controls. The SHR showed a progressive age
      dependent reduction of cardiac work (40 weeks = 5.1+/-0.3, 60 weeks = 4.0+/-0.3,
      80 weeks = 3.8+/-0.2 (mW/g) at baseline conditions) and PCr/ATP-ratio (40 weeks =
      1.82+/-0.06, 60 weeks = 1.69+/-0.05, 80 weeks = 1.59+/-0.09 (PCr/ATP) at baseline
      conditions). Similar results were found for hearts of SHR at high afterload. In
      WKY no significant decline in cardiac work or PCr/ATP-ratio was found under
      either low or under high afterload. The cardiac work capacity of hearts of SHR
      progressively decreases with increasing age and left ventricular hypertrophy.
      This myocardial dysfunction is closely associated with an impaired PCr/ATP-ratio,
      suggesting a decreased energy reserve.

PMID- 11471661
TI  - "Takotsubo" cardiomyopathy with a significant pressure gradient in the left
      ventricle.

PMID- 11471662
TI  - Total thyroidectomy: the procedure of choice for multinodular goitre.
AB  - OBJECTIVE: To review our experience of total thyroidectomy for bilateral
      multinodular goitre. DESIGN: Prospective open study. SETTING: Teaching hospital,
      Malaysia. SUBJECTS: 98 consecutive patients whose bilateral multinodular goitres
      were treated by total thyroidectomy, January 1998-November 1999. INTERVENTION: A
      revised technique of total thyroidectomy in which more attention than is
      customary was paid to the exposure and safety of the laryngeal nerves and the
      parathyroid glands. All patients had at least 1 parathyroid gland
      autotransplanted. MAIN OUTCOME MEASURES: Morbidity and mortality RESULTS: There
      were no injuries to the recurrent laryngeal nerves and no patient developed
      persistent hypocalcaemia; 27/98 developed transient hypocalcaemia, but this had
      settled by 6 months postoperatively. 59 patients had persistent symptoms of
      pressure preoperatively, and these all resolved by 3 months postoperatively. 6
      patients had occult malignant disease discovered on histological examination, and
      3 developed minor wound infections. CONCLUSIONS: Total thyroidectomy is the
      procedure of choice for bilateral multinodular goitres, provided that sufficient
      attention is paid to the preservation of the laryngeal nerves and the parathyroid
      glands.

PMID- 11471663
TI  - Recurrent papillary thyroid cancer: analysis of prognostic factors including the
      histological variant.
AB  - OBJECTIVE: To analyse the factors that influence the development of recurrent
      papillary thyroid carcinoma, including the histological variant. DESIGN:
      Retrospective study. SETTING: Teaching hospital, Spain. SUBJECTS: 200 patients
      who had papillary thyroid cancers resected between 1970 and 1995. MAIN OUTCOME
      MEASURES: Prognostic factors and disease-free interval assessed by univariate and
      multivariate analysis. RESULTS: All patients were followed up for a mean of 9
      years (range 4-29). 54 patients presented with recurrent disease (27%) of whom 19
      (35%) died of their disease. 5-year, 10-year, and 15-year survival for those with
      recurrent disease were 75%, 68%, and 60%, respectively. The corresponding figures
      for the whole series were 93%, 90%, and 84%. The significant variables on
      multivariate analysis were completeness of resection (p = 0.002), extrathyroid
      involvement (p < 0.002), presence of lymph node metastases (p = 0.002), and
      histological variant of the carcinoma (P < 0.001). CONCLUSION: Using these risk
      factors it is possible to draw up a prognostic index and classify patients as
      being at low, medium, or high risk of recurrence.

PMID- 11471664
TI  - Metastases to the para-aortic lymph nodes in adenocarcinoma of the cardia.
AB  - OBJECTIVE: To find out the extent of involvement of the para-aortic nodes in
      patients with adenocarcinoma of the gastric cardia. DESIGN: Open prospective
      study. SETTING: Teaching hospital, Italy. SUBJECTS: 23 patients with advanced
      adenocarcinoma of the cardia (type II, n = 10, and type III, n = 13) who were
      treated by total gastrectomy with resection of the distal oesophagus and extended
      lymphadenectomy (D4) between January 1997 and June 1999. These were compared with
      21 patients with advanced carcinoma of the proximal third of the stomach who had
      total gastrectomy with D4 lymphadenectomy during the same period. Lymph nodes
      were retrieved immediately postoperatively and assigned to the appropriate
      station according to the classification of the Japanese Research Society for
      Gastric Cancer. MAIN OUTCOME MEASURES: Number of para-aortic and other nodes
      involved. RESULTS: 22 of the 23 patients had lymph node metastases, and in 5 the
      para-aortic nodes were involved (N4). N3 lymph nodes were involved in only 1
      patient, despite involvement of para-aortic nodes. Among the 5 patients with N4
      metastases, 1 had only N1 metastases in addition, with no involvement of N2 or N3
      nodes. Patients with involved N4 nodes had more nodes involved overall than those
      who did not (mean (SD) 17 (5) compared with 8 (12)). CONCLUSIONS: 5/23 patients
      with advanced carcinoma of the cardia had involved para-aortic nodes. This may
      have some prognostic value, but larger studies of D4 lymphadenectomy specimens is
      required.

PMID- 11471665
TI  - Health-related quality of life before and after gastrointestinal surgery.
AB  - OBJECTIVE: To assess the impact of surgical treatment on health-related quality
      of life (QoL) and its various dimensions in four common gastrointestinal
      diseases, to compare it with that of the general population, and to assess the
      relationship between the patient's and the surgeon's satisfaction. DESIGN:
      Prospective, observational study. SETTING: Tertiary care centre, Finland.
      PATIENTS: 131 patients, of whom 77 had cholecystectomy, 20 fundoplication, 20
      incisional herniorrhaphy, 12 large bowel resection, and 2 construction of a stoma
      only because of unresectable colorectal cancer. INTERVENTIONS: Routine operative
      treatment of four gastrointestinal diseases. MAIN OUTCOME MEASURES: QoL measured
      by a generic 15-dimensional instrument. RESULTS: The health-related QoL improved
      postoperatively in the entire group. Discomfort, symptoms, and vitality were all
      reduced at 2 months, whereas bowel movements, eating, and usual activities had
      been restored at 12 months. The health related QoL was comparable with that of
      the general population at 12 months except for breathing and sleeping. The
      pattern of recovery varied among diagnostic subgroups, being most improved in
      patients operated on for biliary disease, those aged 60 years or younger, women
      and otherwise previously healthy patients. There was a close agreement between
      the patient's and the surgeon's opinion of outcome. CONCLUSIONS: Gastrointestinal
      surgery improves quality of life. Separating a generic health-related QoL measure
      into dimensions allows a more appropriate estimation of quality of life than a
      single index score. Because some dimensions were made worse soon after operation
      and some were restored slowly, a minimum 12-month follow-up may be needed to
      assess the effect of gastrointestinal surgery on health- related QoL.

PMID- 11471666
TI  - Secondary peritonitis: severity of disease and activation of peritoneal cells.
AB  - OBJECTIVE: To compare the degree of the inflammatory response of human peritoneum
      with the severity of peritonitis. DESIGN: Clinical laboratory study. SETTING:
      University hospital, Germany. SUBJECTS: 15 patients with diffuse secondary
      peritonitis and 5 having conventional cholecystectomy (controls) had peritoneal
      specimens taken from the site of incision. MAIN OUTCOME MEASURES: Correlation
      between presence of indicators of the inflammatory response: interleukin 1 (IL
      1), interleukin 6 (IL-6), intercellular adhesion molecule-1 (ICAM-1),
      antibacterial protein (defensin 3 reflecting the activation of granulocytes), the
      antibody clone HAM 56 (for detection of local macrophages), and antibodies
      against macrophage migration inhibiting factor (MIF)-related proteins 8 and 14
      (MRP 8 and 14), and clinical state evaluated by the Mannheim Peritonitis Index
      (MPI), the Peritonitis Index Altona II (PIA II) and the Acute Physiology Score
      (APS). C-reactive protein (CRP) concentrations were measured preoperatively in
      the serum. RESULTS: Expression of MRP 8 and 14, HAM 56, and defensin 3 was
      significantly higher in patients with peritonitis than in controls (p < 0.05).
      Expression of IL-1 and IL-6 was almost undetectable. ICAM-1 expression correlated
      significantly with phagocytic activation. There was no correlation between
      clinical scores, CRP, and immunohistochemically detectable variables. CONCLUSION:
      The pattern of peritoneal inflammatory reactions is relatively uniform and does
      not correlate with the clinical grading of severity.

PMID- 11471667
TI  - Preoperative oesophageal motor activity does not predict postoperative dysphagia.
AB  - OBJECTIVE: To evaluate the ability of preoperative manometric examinations to
      predict temporary or permanent dysphagia after antireflux procedures. DESIGN:
      Retrospective study. SETTING: Teaching hospital, Sweden. SUBJECTS: 191 patients
      who had partial fundoplication. INTERVENTIONS: Stationary manometry with a
      perfused catheter system. MAIN OUTCOME MEASURES: Correlation between preoperative
      manometric examinations and the incidence of dysphagia before and after
      operation. RESULTS: 98 of 191 patients had dysphagia preoperatively (51%), but 52
      of the 98 had no stricture or motor disorder to explain it; 25 of 59 patients
      with motor disorders shown manometrically (42%) did not complain of dysphagia.
      The number of patients with dysphagia was reduced to 43 postoperatively. 8 who
      did not complain of dysphagia preoperatively did so postoperatively; 4 of 8 had
      defective peristalsis and 4 had normal preoperative tracings. CONCLUSIONS:
      Manometric examination does not help us to understand the mechanism of
      preoperative dysphagia, nor does it predict who will develop dysphagia
      postoperatively.

PMID- 11471668
TI  - Effect of ursodeoxycholate in University of Wisconsin solution on long term
      preservation of rat livers.
AB  - OBJECTIVE: To find out whether the addition of ursodeoxycholate (UDC) to
      University of Wisconsin (UW) solution reduces injury during preservation of the
      liver. DESIGN: Controlled laboratory study. SETTING: University hospital,
      Germany. MATERIALS: Preserved livers from 12 rats. METHODS: Livers were flushed
      with 10 ml of ice-cold (0-1 degrees C) UW or iso-osmolar UW containing 5 mmol/l
      UDC. After preservation for 30 hours at 0-1 degrees C and 1 hour at 22 degrees C
      the livers were reperfused for 4 hours. Aspartate amino-transaminase, alanine
      aminotransferase, glutamate lactate dehydrogenase, and white blood cell (WBC) and
      platelet counts were measured during reperfusion. Bile flow and total bile salt
      secretion rate were also measured. RESULTS: Addition of UDC to UW reduced the
      release of liver enzymes, slightly increased platelet adherence, and reduced bile
      flow and bile salt secretion rate. CONCLUSION: The membrane-stabilising effect of
      UDC may explain the reduction in enzyme release. However, liver function, as
      expressed by bile salt secretion rate and bile flow was adversely affected.

PMID- 11471669
TI  - Inguinal herniorrhaphy with an undetached strip of external oblique aponeurosis:
      a new approach used in 400 patients.
AB  - OBJECTIVE: To describe my experience with a technique of hernia repair in which
      the posterior wall of the inguinal canal is strengthened with an undetached strip
      of the external oblique aponeurosis to give physiologically active and strong
      posterior wall. DESIGN: Retrospective open study. SETTING: Medical college and
      district hospital, India. SUBJECTS: 400 patients operated on 1983-99, 106 of whom
      have been followed up for more than 10 years. INTERVENTION: After the sac has
      been excised, a strip of external oblique aponeurosis is partly separated from
      its medial leaf, keeping its continuity intact at either end. This is sutured to
      the inguinal ligament below, and the arch of the muscle above, behind the cord,
      to form a new posterior wall. MAIN OUTCOME MEASURES: Morbidity and hospital stay.
      RESULTS: No patient had severe pain postoperatively and nearly all patients (n =
      396) were free of pain and discomfort after the second postoperative day. 340
      patients (85%) were discharged by the 4th postoperative day, and most returned to
      normal activities within two weeks. There was one early haematocoele, and 1
      recurrence at 2 years. CONCLUSIONS: The operation is easy to do, does not require
      mesh, and gives results equivalent to those reported for mesh. It is therefore a
      good option for repair of an inguinal hernia.

PMID- 11471670
TI  - Postural stability after inguinal herniorrhaphy under local infiltration
      anaesthesia.
AB  - OBJECTIVE: To investigate postural stability in patients after inguinal
      herniorrhaphy under local infiltration anaesthesia, to see if the anaesthetics
      and analgesics used influenced it and therefore hindered early discharge. DESIGN:
      Open study. SETTING: Teaching hospital, Denmark. SUBJECTS: 55 patients listed for
      elective inguinal herniorrhaphy. INTERVENTIONS: Preoperative and intraoperative
      infiltration anaesthesia by bupivacaine 2.5 mg/ml (median dose 41 ml, range 30-84
      ml), and sedation with midazolam intraoperatively (median dose 3 mg, range 0-10
      mg). Lichtenstein tension-free technique with polypropylene mesh repair
      (Prolene). Measurement of postural stability before operation and 30 and 60
      minutes afterwards using the "Basic Balance Master" system, and balance assessed
      by visual analogue scale and verbal rating scale. MAIN OUTCOME MEASURES: Postural
      stability and subjectively assessed balance. RESULTS: Dynamic postural stability
      was impaired 30 min (p < 0.05), but not 60 minutes postoperatively. All but two
      patients were discharged shortly after the measurement at 60 minutes, because of
      pain in one and an attack of asthma in the other. Balance also returned to normal
      within an hour. CONCLUSION: Objectively measured postural stability and
      subjectively assessed balance return to normal within 60 minutes after inguinal
      herniorrhaphy under local infiltration anaesthesia, thereby permitting early
      discharge.

PMID- 11471671
TI  - Deep prosthesis infection in incisional hernia repair: predictive factors and
      clinical outcome.
AB  - OBJECTIVE: To evaluate the incidence of prosthetic infection in incisional hernia
      repairs, to determine whether there are any factors associated with prosthetic
      infection and to describe the clinical outcome. DESIGN: Retrospective clinical
      study. SETTING: Teaching hospital, Germany. SUBJECTS: 121 consecutive patients
      who underwent incisional hernia repair in our department from December 1994 to
      December 1999. INTERVENTION: Hernia repair by implantation of an alloplastic
      prosthesis by the Stoppa-Rives technique. MAIN OUTCOME MEASURES: Postoperative
      deep prosthetic infection and associated factors. RESULTS: All 121 patients had
      the mesh implanted in the subfascial plane, 77 had a polypropylene mesh (Prolene)
      (64%), 7 had a polyester mesh (Mersilene) (6%), and 37 patients had a expanded
      polytetrafluoroethylene patch (ePTFE, Gore-Tex) (31%). Postoperatively the mesh
      became infected in 8 patients (7%), a mean of 4.5 months (range 0.5-16) after
      hernia repair. All three infected ePTFE patches had to be removed whereas
      drainage was sufficient treatment for the infected polypropylene and polyester
      meshes. CONCLUSION: Once a mesh infection is verified adequate drainage seems to
      be sufficient for polypropylene and polyester meshes but ePTFE patches should be
      removed.

PMID- 11471672
TI  - Modified technique for repairing large incisional hernias.

PMID- 11471673
TI  - Sentinel node biopsy in male breast cancer: future standard treatment?

PMID- 11471674
TI  - Alambda-amyloidosis of the gastrointestinal tract with recurrent incomplete ileus
      and gastrointestinal haemorrhage.

PMID- 11471675
TI  - Total thyroidectomy for hereditary medullary thyroid carcinoma 12 years after
      correction of Hirschsprung's disease.

PMID- 11471676
TI  - Struma ovarii: report of two cases and clinical review.

PMID- 11471677
TI  - Rupture of the auricle of the right atrium of the heart and pericardium after
      blunt trauma.

PMID- 11471678
TI  - Malignant degeneration: an unusual complication of pilonidal sinus disease.

PMID- 11471679
TI  - Negative side-effects of retention sutures: transcutaneous placement versus other
      options.

PMID- 11471680
TI  - Treatment of arsenic in Bangladesh well water using a household co-precipitation
      and filtration system.
AB  - Laboratory and field tests were conducted to evaluate the effectiveness of a
      household filtration process and investigate the effects of phosphate and
      silicate on the removal of arsenic from Bangladesh groundwater by ferric
      hydroxides. Fe/As ratios of greater than 40 (mg/mg) were required to reduce
      arsenic to less than 50 microg/L in Bangladesh well water due to the presence of
      elevated phosphate and silicate concentrations. The household filtration process
      included co-precipitation of arsenic by adding a packet (approximately 2 g) of
      ferric and hypochlorite salts to 20 L of well water and subsequent filtration of
      the water through a bucket sand filter. A field demonstration study was performed
      to test the treatment system in seven households in Bangladesh in March and April
      2000. Experimental results obtained from the participating families proved that
      the household treatment process removed arsenic from approximately 300 microg/L
      in the well water to less than 50 microg/L. The participating families liked this
      simple and affordable process and used it to prepare clean water for drinking and
      cooking. A larger scale field test is currently underway.

PMID- 11471681
TI  - Influence of sediment and pore-water composition on nitrite accumulation in a
      nitrate-perfused freshwater sediment.
AB  - Anaerobic nitrate consumption was accompanied by the accumulation of nitrite in
      the range of 3-52 micromoll(-1) in laboratory sediment cores continuously
      perfused with nitrate from below. Highest interstitial nitrite concentrations
      were observed in organically poor sediment cores with a low extractable protein
      content. Supplemented with an additional source of fixed nitrogen (ammonium), the
      nitrate-perfused sediments exhibited considerably lower nitrite concentrations
      than the respective control treatments. The simultaneous addition of ammonium and
      chloramphenicol, however, resulted in high nitrite concentrations. This suggests
      that in the absence of chloramphenicol an ammonium-fuelled bacterial protein de
      novo synthesis prevented the accumulation of nitrite in the course of anaerobic
      nitrate consumption. Additional DOC (glucose, methanol) generally increased the
      anaerobic nitrate consumption rate and the interstitial nitrite concentrations.
      The different scales of these increases were probably related to the
      degradability of the respective DOC compound and to the taxonomic composition of
      the microbial community evolving under different feeding regimes.

PMID- 11471682
TI  - Mechanism of degradation of the quality of natural water in the Lakes Region of
      the Ethiopian rift valley.
AB  - The natural waters of the Lakes Region in the Main Ethiopian Rift (MER) show
      serious problems of chemical quality. The high content of fluoride reaches 300
      mgl(-1) and affects the health of the population who live in this area.
      Furthermore, the alkaline and sodic characteristics (8<pH<10 and 0.9 x 10(-4) <
      Na < 0.35 Ml(-1)) of these waters destroy the soil for agricultural use. This
      geochemical study is conducted using analytical data issued from literature
      (UNDP, 1973: Chernet, 1982) and several field sampling and laboratory analyses
      completed during the last 4 yr. Chemical analyses of 320 samples taken throughout
      the region have been analysed using the computer software AQUA for geostatistic,
      statistic, chemical equilibria and simulation of evaporative concentration
      process. The results show that the waters issuing from volcanic rocks are
      characterised by a positive alkalinity residual of calcite. When they concentrate
      due to the effect of climate, the precipitation of calcite causes a decrease in
      the chemical activity of calcium. This results in an increase in solubility of
      fluoride, previously controlled by equilibrium with CaF, and the element
      concentrates without being significantly affected by the precipitation of
      fluorite. As water concentrates, the low concentration of dissolved calcium
      emphasises the alkaline characteristics. As a consequence, the pH reaches very
      high values (9-10) which make the waters unsuitable for agriculture. The adverse
      elements. namely fluoride, sodium, and alkalinity accumulate in the lower zones
      of the basins. The acquisition of high fluoride content and the alkaline-sodic
      characteristics depends primarily on the unbalanced initial stage between the
      carbonate alkalinity and calcium [(HCO3) > 2(Ca + Mg)]. which results from the
      weathering and dissolution of the volcanic rocks. The predictive qualities of the
      model AQUA were tested in the context of this region. A simulation of the
      concentration of the waters by evaporation has shown chemical variations
      relatively similar to those obtained with field data which include the minor
      chemical elements such as the fluoride or the dissolved silica. For field data,
      enrichment is more variable and may represent localised conditions of
      mineralization. This model is then used to study a method of defluoridation by
      supplying these waters with calcium in the form of gypsum. This method also
      allows the reduction of the alkalinizing and sodifying characteristics of the
      waters without reaching the fluoride standard concentration accepted for drinking
      waters. For drinking purpose, waters of the Ethiopian rift should undergo another
      method of defluoridation.

PMID- 11471683
TI  - Evaluation of new methods for the monitoring of alkalinity, dissolved hydrogen
      and the microbial community in anaerobic digestion.
AB  - New methods for spectrophotometric alkalinity measurement, dissolved hydrogen
      monitoring and for obtaining a fingerprint of the microbial community were
      evaluated as tools for process monitoring in anaerobic digestion. The anaerobic
      digestion process was operated at organic loading rates of 1.5, 3.0 and 4.5 g
      volatile solids l(-1)d(-1) and subjected to pulse loads of carbohydrate, lipid,
      protein and a mixed sludge substrate. The spectrophotometric alkalinity
      monitoring method showed good agreement with traditional titrimetric alkalinity
      monitoring and has the advantage of being easy to modify to on-line monitoring
      applications. The on-line monitoring of dissolved hydrogen gave valuable
      information about approaching process overload and can be a good complement to
      the conventional monitoring of volatile fatty acids. Changing process conditions
      were also reflected in the microbial fingerprint that could be achieved by
      partitioning in two-phase systems. The investigated methods showed potential for
      application in increasing our understanding of the anaerobic digestion process as
      well as for being applicable for monitoring in the complex environment of full
      scale anaerobic digestion processes.

PMID- 11471684
TI  - Kinetic characteristics of bacterial azo-dye decolorization by Pseudomonas
      luteola.
AB  - A Pseudomonas luteola strain expressing azoreductase activity was utilized to
      remove the color of an azo dye (reactive red 22) from contaminated solutions. The
      effects of substrate concentrations, medium compositions, and operation
      parameters (e.g., pH, temperature, dissolved oxygen, etc.) on decolorization of
      the azo dye by a P. luteola strain were systematically investigated to reveal the
      key factors that dominate the performance of azo-dye decolorization. The
      metabolites resulting from bacterial decolorization were analyzed by high
      performance liquid chromatography (HPLC) and mass spectrometery (MS). The results
      show that the dissolved oxygen and glucose concentration retarded decolorization
      of reactive red 22 by P. luteola. The optimal azo-dye decolorization occurred at
      37 degrees C, while more rapid decolorization took place over pH 7-9. Yeast
      extract and tryptone strongly enhanced the decolorization. The Michaelis-Menten
      model can satisfactorily describe the dependence of specific decolorization rate
      on the concentration of substrate (reactive red 22 or yeast extract).
      Decolorization of the azo dye by intact cells of P. luteola was essentially
      independent of the growth phase, whereas the azoreductase activity of the cell
      free extract decreased in the order of late-stationary phase > early-stationary
      phase > mid-log phase. This suggests that mass transfer of the azo dye across the
      cell membrane may be the rate-limiting step. The HPLC and MS analyses suggest
      that both partial reduction and complete cleavage of the azo bond could
      contribute to decolorization of reactive red 22 by P. luteola.

PMID- 11471685
TI  - Model-based evaluation of two BNR processes--UCT and A2N.
AB  - The activity of denitrifying P-accumulating bacteria (DPB) has been verified to
      exist in most WWTPs with biological nutrient removal (BNR). The modified UCT
      process has a high content of DPB. A new BNR process with a two-sludge system
      named A2N was especially developed to exploit denitrifying dephosphatation. With
      the identical inflow and effluent standards, an existing full-scale UCT-type WWTP
      and a designed A2N process were evaluated by simulation. The used model is based
      on the Delft metabolical model for bio-P removal and ASM2d model for COD and N
      removal. Both processes accommodate denitrifying dephosphatation, but the A2N
      process has a more stable performance in N removal. Although excess sludge is
      increased by 6%, the A2N process leads to savings of 35, 85 and 30% in aeration
      energy, mixed liquor internal recirculation and land occupation respectively, as
      compared to the UCT process. Low temperature has a negative effect on growth of
      poly-P bacteria, which becomes to especially appear in the A2N process.

PMID- 11471686
TI  - A study on the distribution of chlorination by-products (CBPs) in treated water
      in Korea.
AB  - Fifteen chlorination by-products were analyzed in 416 water samples collected
      from 35 water treatment plants in Korea from 1996 to 1998. These samples were
      divided into five groups according to water sources (Han-river, Nakdong-river,
      Youngsan-river, Kum-river and Cheju) and detected CBPs were classified into six
      classes (trihalomethanes; THMs, haloacetic acids; HAAs, haloacetonitriles: HANs
      haloketones; HKs, chloralhydrate; CH, chloropicrin; CP) and then, it was observed
      the detection tendency and frequency of CBPs in each water source. The total
      concentration of CBPs in treated water from Nakdong-river or Han-river was higher
      than those from the other rivers. And the distribution pattern of each class of
      CBPs was similar in all water sources. THMs were the highest portion in the range
      of 40-50%, and HAAs and HANs were 28-35 and 9-15%, respectively. And there was a
      strong correlation between HANs and HKs (r=0.813). Each and total concentrations
      of CBPs showed to be more affected by the water source in two-way analysis of
      variance (two-way ANOVA) among the concentration of CBPs, the source of water and
      season.

PMID- 11471687
TI  - The influence of pH and cadmium sulfide on the photocatalytic degradation of 2
      chlorophenol in titanium dioxide suspensions.
AB  - The influence of pH and cadmium sulfide on the photocatalytic degradation of 2
      chlorophenol (2-CP) in titanium dioxide suspensions was investigated to evaluate
      the feasibility of mixed semiconductors on the photodegradation of chlorinated
      organics in aqueous solution. Apparent first-order rate constants (k(obs)) and
      initial rate constants were used to evaluate the degradation efficiency of 2-CP.
      Higher degradation efficiency of 2-CP was observed at higher pH values. The
      apparent pseudo-first-order rate constant was 0.036 min(-1) at pH 12.5 in TiO2/UV
      system, while a 2- to 9-fold decrease in k(obs) was observed over the pH range of
      2.5-9.5. The addition of phosphate buffer solutions at different pH values have
      different effects on the degradation of 2-CP. H2PO4- has little effect on the
      photodegradation of 2-CP, while HPO4(2-) could inhibit the photodegradation
      efficiency of 2-CP. Chlorocatechol, hydroquinone, benzoquinone and phenol were
      identified as the predominant aromatic intermediates for the photocatalytic
      degradation of 2-CP. Moreover, less aromatic intermediates at higher pH were
      observed. Direct oxidation contributed significantly to the photodegradation of 2
      CP. An addition of a semiconductor decreased the initial and apparent first-order
      rate constants of 2-CP. The cutoff of wavelength of 320nm could diminish the
      contribution of direct photolysis of 2-CP. The combination of cadmium sulfide and
      titanium dioxide can lead to an enhanced rate of disappearance of 2-CP compared
      to those in single semiconductor system. A 1.2 to 2.5-fold increase in rate
      constant in coupled semiconductor system relative to the single semiconductor
      system was obtained.

PMID- 11471688
TI  - Pattern recognition techniques for the evaluation of spatial and temporal
      variations in water quality. A case study: Suquia River Basin (Cordoba
      Argentina).
AB  - We report a comparative study using three different chemometric techniques to
      evaluate both spatial and temporal changes in Suquia River water quality, with a
      special emphasis on the improvement obtained using discriminant analysis for such
      evaluation. We have monitored 22 parameters at different stations from the upper,
      middle, and beginning of the lower river basin during at least two years
      including 232 different samples. We obtained a complex data matrix, which was
      treated using the pattern recognition techniques of cluster analysis (CA), factor
      analysis/principal components (FA/PCA). and discriminant analysis (DA). CA
      renders good results as a first exploratory method to evaluate both spatial and
      temporal differences, however it fails to show details of these differences.
      FA/PCA needs 13 parameters to point out 71% of both temporal and spatial changes,
      consequently data reduction from FA/PCA in this case is not as considerable as
      expected. However, FA/PCA allows to group the selected parameters according to
      common features as well as to evaluate the incidence of each group on the overall
      change in water quality, specially during the analysis of temporal changes. DA
      technique shows the best results for data reduction and pattern recognition
      during both temporal and spatial analysis. DA renders an important data reduction
      using 6 parameters to afford 87% right assignations during temporal analysis.
      Besides, it uses only 5 parameters to yield 75% right assignations during the
      spatial analysis of four different basin areas. DA allowed us to greatly reduce
      the dimensionality of the starting data matrix, pointing out to a few parameters
      that indicate the biggest changes in water quality as well as variation patterns
      associated with seasonal variations, urban run-off, and pollution sources,
      presenting a novel approach for water quality assessments.

PMID- 11471689
TI  - Optimisation of combined coagulation and microfiltration for water treatment.
AB  - The effect of upstream coagulant dosing for full-flow microfiltration of an
      upland-reservoir water has been investigated. The process, run under conditions
      of constant flux and pH and based on a ferric salt, is compared with a published
      study of another full-flow process based on alum dosing and operated at constant
      pressure and coagulant concentration. The current study includes data for the
      residual deposit remaining following backflushing by reverse flow. Results are
      presented in terms of the specific-cake resistance (R'o, m(-2)) as a function of
      pH or coagulant dose. Reasonable correlation with classical cake filtration
      theory was obtained, such that R' was assumed to be independent of run time and
      cake thickness. The following trends have been noted: The optimum pH for the alum
      based system appears to be between 7.5 and 8 on the basis of cake resistance. The
      effect of coagulant dose between 18 and 71 microM Fe3+ is much more significant
      than a change in pH between 5 and 9 for the alum system: a 53-fold increase in
      specific flux compared with a 7-fold increase with reference to the limiting R'o
      values at pH 4.8 and 7.7. A low coagulant dose (0.018mM, 1.0 mg l(-1) Fe3+)
      appears to have a slightly detrimental effect on downstream microfiltration
      operation. The low coagulant doses apparently cause incomplete aggregation of
      colloidal particles such that internal fouling of the membrane takes place. The
      residual (cleaning cycle) deposit resistance followed roughly the same trend as
      the backflush cycle-cake resistance with coagulant concentration, but with a much
      reduced value (about 16 times lower, on average). An optimum coagulant dose of
      0.055 mM (3.1 mg/l) Fe3+ can be identified on the basis of operational cost based
      on coagulant cost and cake resistance, all other aspects of the system being
      substantially unchanged. It is concluded that coagulation with downstream
      microfiltration offers a cost-effective means of removing natural organic matter,
      achieving a THMFP removal of around 80% at the optimum dose.

PMID- 11471690
TI  - Toxicity of Hg, Cu, Cd, and Cr on early developmental stages of Ciona
      intestinalis (Chordata, Ascidiacea) with potential application in marine water
      quality assessment.
AB  - The toxicity of mercury, copper, cadmium and chromium on sperm viability,
      fertilisation, embryogenesis and larval attachment of Ciona intestinalis was
      examined. Fertilisation rate (FR) showed a small decrease even at the highest
      metal concentration tested. The median effective concentrations (EC50) reducing
      rates of embryogenesis and larval attachment by 50% were 54 microg Hg/l (0.27
      microM), 46 microg Cu/l (0.72 microM), 838 microg Cd/l (7.46 microM), 10,318
      microg Cr/l (198 microM), and 35 microg Hg/l (0.18 microM), 34 microg Cu/l (0.54
      microM) and 11,755 microg Cr/l (226 microM), respectively. Therefore, Hg is three
      times more toxic than Cu (on a molar basis), ca. 30 times more toxic than Cd and
      ca. 1000 times more toxic than Cr to early stages of C. intestinalis. Rates of
      larval attachment and embryogenesis were the most sensitive endpoints, although
      the latter is more advisable for routine assessment of seawater quality because
      of its greater simplicity. In addition to bivalves and sea-urchins, ascidian
      embryos can provide biological criteria for seawater quality standards taking
      into account the sensitivity of a chordate and contributing to the detection of
      harmful chemicals with no marked effect on the species currently in use in
      seawater quality bioassays.

PMID- 11471691
TI  - Evaluation of kinetic coefficients using integrated monod and haldane models for
      low-temperature acetoclastic methanogenesis.
AB  - The integrated Monod and Haldane models were used to evaluate the kinetic
      coefficients and their standard deviations using the methane accumulation curves
      of low-temperature acetoclastic methanogenesis. The linear and exponential
      approximations and the limitations of their applicability were deduced from the
      integrated models. The samples of lake sediments and biomass taken from a low
      temperature upflow anaerobic sludge blanket (UASB) reactor were used as inoculum
      in batch assays for acetate methanation. In comparison, the Monod and Haldane
      models were applied to evaluate the kinetic coefficients for mesophilic
      acetoclastic methanogenesis accomplished by the pure culture of Methanosarcina
      barkeri strain MS. The Monod and Haldane models and their approximations were
      fitted by using non-linear regression. For the wide range of initial
      acetateconcentrations (4.2-84 mM: 5-100 mM) applied to the UASB biomass at 11 and
      22 degrees C and for the lake sediment samples at 6 and 15 degrees C, a better
      fit was obtained with the Haldane models and their exponential approximations,
      respectively. For the lake sediments the values of inhibition coefficients
      decreased at decreasing temperatures. At the highest temperature of 30 degrees C
      no difference was found between the Haldane and Monod models and the simpler
      Monod model should be preferred. The values of the maximum growth rate of biomass
      were highest at 30 degrees C (lake sediment) and 22 degrees C (the UASB biomass)
      being in a range presented in the literature for mesophilic acetoclastic
      methanogenesis.

PMID- 11471692
TI  - Impact of temperature on nitrification in biological activated carbon (BAC)
      filters used for drinking water treatment.
AB  - The impact of temperature on nitrification in biological granular activated
      carbon (GAC) filters was evaluated in order to improve the understanding of the
      nitrification process in drinking water treatment. The study was conducted in a
      northern climate where very cold water temperatures (below 2 degrees C) prevail
      for extended periods and rapid shifts of temperature are frequent in the spring
      and fall. Ammonia removals were monitored and the fixed nitrifying biomass was
      measured using a method of potential nitrifying activity. The impact of
      temperature was evaluated on two different filter media: an opened superstructure
      wood-based activated carbon and a closed superstructure activated carbon-based on
      bituminous coal. The study was conducted at two levels: pilot scale (first-stage
      filters) and full-scale (second-stage filters) and the results indicate a strong
      temperature impact on nitrification activity. Ammonia removal capacities ranged
      from 40 to 90% in pilot filters, at temperatures above 10 degrees C, while more
      than 90% ammonia was removed in the full-scale filters for the same temperature
      range. At moderate temperatures (4-10 degrees C), the first stage pilot filters
      removed 10-40% of incoming ammonia for both media (opened and closed
      superstructure). In the full-scale filters, a difference between the two media in
      nitrification performances was observed at moderate temperatures: the ammonia
      removal rate in the opened superstructure support (more than 90%) was higher than
      in the closed superstructure support (45%). At low temperatures (below 4 degrees
      C) both media performed poorly. Ammonia removal capacities were below 30% in both
      pilot- and full-scale filters.

PMID- 11471693
TI  - Stabilized landfill leachate treatment by combined physicochemical-nanofiltration
      processes.
AB  - Landfill leachate is a complex wastewater which the composition and concentration
      of contaminants are influenced by the type of waste deposited and the age of
      landfill. In the last years, several processes or process combinations were
      developed and tested to reach requirements for the discharge of leachate. Among
      the new processes, membrane processes are considered as promising: reverse
      osmosis is one of the most widely used treatment in the Northwestern European
      countries and nanofiltration is gained in popularity during the last 5 years.
      Successful application of membrane technology for the treatment of landfill
      leachates, requires efficient control of membrane fouling. Two organic membranes
      of nanofiltration were used for pilot-scale testing. Leachates were subject to
      several pretreatments (pH modification, prefiltration and coagulation with FeCl3)
      to remove potential foulants including dissolved organic and inorganic
      substances, colloidal and suspended particles. These pretreatments do not enhance
      the performances (retention and permeation flux) of membranes because the pH
      range and the presence of Fe3+ ions contribute greatly to change the
      characteristics of organic matter and the surface charges of membranes. However,
      the results show that nanofiltration is sufficient to eliminate refractory COD,
      the permeates have a COD lower than the requirements for discharge.

PMID- 11471694
TI  - Removal of dissolved organic compounds in fixed-bed columns: evaluation of low
      rank coal adsorbents.
AB  - Characterisation of a range of Victorian low-rank coal (VLRC) based and
      commercial adsorbents under continuous flow conditions was conducted in down flow
      fixed-bed columns. The effect of bed depth, hydraulic loading and initial
      concentration of the adsorbate 4-nitrophenol (4-NP) was studied. Prediction of
      the performance of the columns using bed-depth/service time analysis showed good
      agreement with the experimental results. The VLRC-based activated carbons gave
      lower service times for removal of 4-NP compared with the coconut-based
      commercial activated carbon Picactif. However, they showed comparable efficiency
      in terms of bed volumes treated and carbon usage rate (CUR). The VLRC-activated
      power station char (APSC) showed the lowest CUR of 0.57 g/L in comparison with
      0.62 and 3.61 g/L exhibited by the commercial carbons Picactif and Hydraffin,
      respectively. The power station char (PSC) and Auschar gave poor CUR of 11.23 and
      75.36 g/L, respectively. Three adsorbents were evaluated for the removal of
      natural organic matter (NOM) from aqueous solution. The breakthrough behaviour
      indicated that the pore size distribution of the adsorbents is an important
      physical characteristic for the adsorption of the NOM. There was a non-adsorbable
      fraction of the NOM that was a function of the type of adsorbent. In the presence
      of NOM, Picactif gave longer service time for the removal of 4-NP compared with
      APSC. consistent with the trend obtained in the absence of NOM. However, lower
      breakthrough times (at 10% C0) of 44 and 47% were obtained for APSC and Picactif,
      respectively. Further removal (35%) of 4-NP was achieved over extended operation
      of the beds, however more frequent backwashing was required as a result of the
      biological growth exhibited in the presence of NOM.

PMID- 11471695
TI  - Inactivation of Bacillus subtilis spores and formation of bromate during
      ozonation.
AB  - Inactivation of B. subtilis spores with ozone was investigated to assess the
      effect of pH and temperature, to compare the kinetics to those for the
      inactivation of C. parvum oocysts, to investigate bromate formation under 2-log
      inactivation conditions, and to assess the need for bromate control strategies.
      The rate of B. subtilis inactivation with ozone was independent of pH, decreased
      with temperature (activation energy of 42,100 Jmol(-1)), and was consistent with
      the CT concept. B. subtilis was found to be a good indicator for C. parvum at 20
      30 degrees C, but at lower temperatures B. subtilis was inactivated more readily
      than C. parvum. Bromate formation increased as both pH and temperature increased.
      For water with an initial bromide concentration of 33 microgl(-1), achieving 2
      logs of inactivation, without exceeding the 100 microg l(-1) bromate standard,
      was most difficult at 30 degrees C for B. subtilis and at midrange temperatures
      (10-20 degrees C) for C. partum. pH depression and ammonia addition were found to
      reduce bromate formation without affecting B. subtilis inactivation, and may be
      necessary for waters containing more than 50 microgl(-1) bromide.

PMID- 11471696
TI  - Physico-chemical characteristics of corrosion scales in old iron pipes.
AB  - Corrosion scales play an important role in modifying water quality in drinking
      water distribution systems. The corrosion scales from old iron/steel pipes were
      analyzed for their structure and composition. Scales were studied both before and
      after drying. and goethite, magnetite and lepidocrocite were identified as the
      primary constituents of the dried samples. High concentrations of readily soluble
      ferrous phases were detected in wet-scale samples. The corrosion scales had a
      shell-like, enveloping layer, covering porous deposits of iron oxide phases. Our
      studies were able to identify important differences between corrosion scales
      found in two different water distribution systems. Further studies are needed to
      establish the role of corrosion scales in the mechanism of iron release from
      corroded pipes.

PMID- 11471697
TI  - Effects of temperature and aerial exposure on the BOD of waste zebra mussels
      removed from navigational locks.
AB  - This laboratory study evaluated the effects of temperature and aerial exposure on
      BOD5 (5-day BOD) of waste zebra mussels of the type generated by maintenance
      operations on dams and navigational locks. The term waste zebra mussels includes
      the mussels and their associated debris with the latter including sediment,
      feces, pseudofeces and other small aquatic organisms. The BOD5 of waste zebra
      mussel was evaluated after aerial exposure of 3 and 10 days at temperatures of 5,
      10, and 20 degrees C. The mean BOD5 values for waste zebra mussels in this study
      ranged from 18,500 to 30,600 mg O2/l. Factorial ANOVA analysis revealed that both
      temperature and aerial exposure had a negative effect on waste zebra mussel BOD5
      (P<0.05) but there was no significant interaction effect (P = 0.119). Multiple
      regression analysis predicted that for the range of treatment conditions used in
      this study each 1 degrees C increase in temperature reduced the waste zebra
      mussel BOD5 by 284mg O2/l or 0.93% of the maximum mean BOD5. Each I day increase
      in aerial exposure reduced waste zebra mussel BOD5 by 987 mg O2/l or 3.22% of the
      maximum mean BOD5. Aerial exposure of waste zebra mussels substantially reduces
      waste BOD5.

PMID- 11471698
TI  - Anaerobic degradation and methanogenic inhibitory effects of oleic and stearic
      acids.
AB  - Oleic acid, an 18 carbon acid with one double bond (C18:1) was degraded
      anaerobically to palmitic (C16:0) and myristic (C14:0) acid by-products at 21 C
      by a culture unacclimated to long-chain fatty acids. These by-products were
      degraded to acetate and ultimately to methane. In comparison, no long-chain fatty
      acid by-products were observed in unacclimated anaerobic cultures receiving
      stearic (C18:0) acid although slow removal of stearic acid occurred. Oleic acid
      concentrations above 30mg l(-1) inhibited acetate degradation but stearic acid up
      to 100 mg l(-1) did not inhibit aceticlastic methanogenesis. Hydrogenotrophic
      methanogenesis was slightly inhibited by oleic and stearic acids. A thermodynamic
      basis for comparing anaerobic C18 acid degradation and predicting by-products is
      presented.

PMID- 11471699
TI  - Fate and transport of copper-based crop protectants in plasticulture runoff and
      the impact of sedimentation as a best management practice.
AB  - The fate and distribution of copper-based crop protectants, applied to
      plasticulture tomato fields to protect against disease, were investigated in a
      greenhouse-scale simulation of farming conditions in a coastal environment.
      Following rainfall, 99% of the applied copper was found to remain on the fields
      sorbed to the soil and plants; most of the soil-bound copper was found sorbed to
      the top 2.5 cm of soil between the plasticulture rows. Of the copper leaving the
      agricultural fields, 82% was found in the runoff with the majority, 74%. sorbed
      to the suspended solids. The remaining copper, 18%, leached through the soil and
      entered the groundwater with 10% in the dissolved phase and 8% sorbed to
      suspended solids. Although only 1% copper was found to leave the field, this was
      sufficient to cause high copper concentrations (average 2102+/-433 microg/L total
      copper and 189+/-139 microg/L dissolved copper) in the runoff. Copper
      concentrations in groundwater samples were also high (average 312+/-198 microg/L
      total copper and 216+/-99 microg/L dissolved copper). Sedimentation, a best
      management practice for reducing copper loadings. was found to reduce the total
      copper concentrations in runoff by 90% to a concentration of 245+/-127 microg/L;
      however, dissolved copper concentrations remained stable, averaging 139+/-55
      microg/L. Total copper concentrations were significantly reduced by the effective
      removal of suspended solids with sorbed copper.

PMID- 11471700
TI  - Feasibility of a multi-component additive for efficient control of activated
      sludge filamentous bulking.
AB  - Instantaneous improvement of the settling of bulking filamentous activated sludge
      can be achieved by the addition of a polymer or a large amount (up to 100% of the
      MLSS concentration) of talc powder to the sludge. Long-term improvement relies on
      repeated additions, as these additives have no adverse effects on the causative
      filaments. A multi-component additive was compared to the traditional additives
      in lab-scale activated sludge units using three highly filamentous sludges from
      different industrial treatment plants. The study demonstrated that the multi
      component additive was superior to the traditional remedies. It was shown that,
      in the case of severe filamentous bulking, a single addition of the new additive
      immediately improved sludge settling and exerted a destructive effect on the
      causative filamentous bacteria. Thus, the latter additive also ensured a long
      term sludge sedimentation improvement. The traditional additives exhibited an
      immediate and short-term effect. The novel additive also retarded sludge rising
      due to denitrification and it improved sludge dewaterability. The study revealed
      Nostocoido limicola II, with slightly hydrophobic cell wall, to be somewhat
      resistant to the quaternary ammonium salt present as biocide in the additive.

PMID- 11471701
TI  - Assessing the effectiveness of regulatory controls on farm pollution using
      chemical and biological indices of water quality and pollution statistics.
AB  - Water quality was measured in 42 streams in the Colebrooke and Upper Bann
      catchments in Northern Ireland over the period 1990-1998. Despite ongoing
      pollution control measures, biological water quality, as determined by the
      invertebrate average score per taxon (ASPT) index, did not improve and there was
      no appreciable decline in recorded farm pollution incidents. However, the lack of
      decline in pollution incidents could reflect changes in detection policy, as a
      greater proportion of incidents were recorded from less polluting discharges such
      as farm-yard runoff. In contrast, there was an improvement during 1997 and 1998
      in annual chemical water quality classification based on exceedence values (90th
      percentiles) for dissolved oxygen, ammonium and BOD concentrations. In 1998,
      11.9% of streams were severely polluted compared to 26.2% in 1990, while the
      proportion classed as of salmonid water quality, increased from 40.5% in 1990 to
      59.6% in 1998. Although water quality in 1996 did not improve relative to 1990
      values, there was a notable increasing trend from 1990 in the numbers of samples
      taken during the summer which had good water quality with low ammonium (<0.6mgN
      l(-1)) and high dissolved oxygen (> 70% sat). The trend for samples with low BOD
      (<4 mgl(-1)) was more erratic, but an improvement was apparent from 1994. These
      improvements in chemical water quality suggest that point-source farm pollution
      declined after 1990. The fact that this was not reflected in stream biology may
      reflect the limited time scale for biological recovery. An important factor
      preventing biological recovery may be the high pollution capacity of manures and
      silage effluent, so that even reduced numbers of farm pollution incidents can
      severely perturb stream ecosystems. The intractable nature of farm pollution
      suggests that there is a need to consider an interactive approach to problem
      resolution involving both farmers and regulators.

PMID- 11471702
TI  - Phytoremediation potential of willow trees for aquifers contaminated with ethanol
      blended gasoline.
AB  - Ethanol-blended gasoline has been used in Brazil for 20 years and, probably, is
      going to be more widely used in North America due to the MtBE environmental
      effects on groundwater. The potential impacts caused by the presence of ethanol
      in UST spills are related to the co-solvency effect and the preferential
      degradation of ethanol over the BTEX compounds. These interactions may increase
      the length of dissolved hydrocarbon plumes and the costs associated with site
      remediation. This study investigates the advantages of phytoremediation to
      overcome the problems associated with the presence of ethanol in groundwater
      contaminanted with gasoline-ethanol mixtures. Experiments were performed under
      lab conditions with cuttings of Willow tree (Salix babylonica) cultivated
      hydroponically. Results showed that the cuttings were able to reduce ethanol and
      benzene concentrations by more than 99% in less than a week. The uptake of both
      contaminants was confirmed by blank controls and was significantly related to
      cuttings transpiration capacity. Sorption onto roots biomass also markedly
      affected the behavior of contaminants in solution. Experiments to evaluate
      plants' toxicity to ethanol indicated that plants were only affected when aqueous
      ethanol concentration reached 2000mgl(-1). Results suggest that phytoremediation
      can be a good complement to intrinsic remediation in shallow aquifer sites
      contaminated with ethanol-blended gasoline spills.

PMID- 11471703
TI  - Ferric chloride and lime conditioning of activated sludges: an electron
      microscopic study on resin-embedded samples.
AB  - Ferric chloride and lime conditioning of sewage sludge is usually interpreted in
      terms of enhanced aggregation of sludge components. In this study, transmission
      electron microscopy was used to investigate the conditioning mechanism at a
      submicronic scale. Samples were collected from two municipal wastewater treatment
      plants at different stages of the process, embedded in an epoxy resin, and
      sectioned with an ultramicrotome. Transmission electron microscopy examination of
      thin sections revealed that clumps of crystalloids develop on external surfaces
      of flocs after the application of both conditioners. This precipitate creates a
      rigid structure around the flocs which, upon mechanical dewatering, transmits the
      stresses applied to the inner parts of flocs. The porous structure of the
      precipitate may also participate to the withdrawal of water as a draining media.
      Energy dispersive X-ray spectroscopy revealed that Fe, P, and Ca are the dominant
      elements in the precipitate with Fe/P and Fe/Ca elemental ratios close to 2.8-3
      and 1.1-3, respectively.

PMID- 11471704
TI  - Mobility and profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans in
      sediment of Ya-Er Lake, China.
AB  - The sediment of Ya-Er Lake had been heavily polluted by polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs) from the former chloralkali industry. The
      total amounts of PCDD/Fs and I-TEQ decreased along the water flow direction and
      also decreased from top to bottom layers of sediment cores. Sediment of Pond 1
      was dominated by PCDF. especially TCDF. In contrast, in the other four ponds,
      PCDD dominated in all layers and octachlorinated dibenzo-p-dioxin (OCDD)
      predominated in all of the homologues. When homologue profiles from sediments and
      water samples were compared using principal component analysis (PCA), the first
      two principal components represented 95.2% of the variance in the data. The first
      component explained 75.9% of the variance and the second one 19.3%. Two clusters
      were most distinct, presenting a shift in PCDD/Fs composition from PCDF to
      heptachlorinated dibenzo-p-dioxin (HpCDD) and OCDD in sediments and water from
      Pond I to Ponds 2-5. The pattern variation between Pond I and Ponds 2-5 in Ya-Er
      Lake was most likely due to the change of process in the chemical plant after the
      dams between the ponds were built. The results of the present study also showed
      that log Koc of PCDD/Fs calculated from data of sediment and water in the field
      were comparable with theoretical log Koc. The results also implied that the
      concentrations of PCDD/Fs in water and sediments could be predicted from each
      other by log Koc.

PMID- 11471705
TI  - Biological perchlorate reduction in high-salinity solutions.
AB  - Perchlorate (ClO4-) has been detected in numerous ground and surface waters, and
      has recently been added to the drinking water Candidate Contaminant List in the
      United States. Perchlorate can be removed from drinking water using ion exchange,
      but this results in the production of highly saline (7-12%) perchlorate
      contaminated brines. Perchlorate-degrading microbial enrichments capable of
      growth in highly saline water were obtained by screening six salt water
      environments including marine and lake surface waters, salt marshes, subtidal
      sediments, and a biofilm/sludge from a seawater filter. Perchlorate reduction was
      obtained in three of these samples (seawater, saline lake water, and
      biofilm/sludge) at a salinity of 3%. The salinity range of two of these cultures
      was extended through serial transfers into media having higher salt
      concentrations (3-7%). Growth rates were measured over a salinity range of 1-15%.
      The maximum growth rate measured for the saline lake-water enrichment was 0.060+/
      0.003 d(-1) (doubling time of 11.6+/-0.8 d) at a salinity of 5%. Growth rates
      decreased to 0.037+/-0.002 d(-1) at a salinity of 11%, and no growth was observed
      at salinities of 13 or 15%. These results demonstrate for the first time that
      biological perchlorate reduction is possible in solutions having a salinity
      typical of ion exchange brines.

PMID- 11471706
TI  - Hydrogen bonding and dipolar interactions between quinolines and organic
      solvents. Nuclear magnetic resonance and ultraviolet-visible spectroscopic
      studies.
AB  - Solvatochromic studies on quinoline (Q), 3-cyanoquinoline (CNQ), 3-bromoquinoline
      (BrQ) and 8-hydroxyquinoline (OHQ) in pure solvents and alcohol-cyclohexane
      mixtures have been performed. The results are compared with Proton Nuclear
      Magnetic Resonance, 1H NMR. studies and AMI calculations. Taft and Kamlet's
      solvatochromic comparison method was used to disclose solvent effects in pure
      solvents. These studies shows that the hydrogen bond acceptor ability of the Q
      ring is diminished and its polarity is increased by the presence of the cyano
      group in CNQ and the bromo group in BrQ. In OHQ, intramolecular hydrogen bonding
      has been observed. This interaction is weakened by the interaction with protic
      solvents. The studies in binary mixtures, alcohol-cyclohexane, show solute
      solvent interactions, which compete with solvent self-association in the
      preferential solvation phenomena. Alcohols with strong ability to self-associate
      have less preference toward solvation of these compounds. The association
      constants for solute-ethanol systems were determined by 1H NMR. The results show
      that the solvent hydrogen bond donor ability is the main factor involved in the
      interaction with these solutes at the aza aromatic site.

PMID- 11471707
TI  - Ion solvation and association in LiClO4/sulfolane solution: a vibrational
      spectroscopic and molecular orbital study.
AB  - Solvation interaction and ion association in solutions of lithium
      perchlorate/sulfolane have been studied by using infrared and Raman spectra as a
      function of concentration of lithium perchlorate. The band changes of
      antisymmetric OSO stretch, antisymmetric CSC stretch, -SO2 wag and twist suggest
      that there is an interaction between Li+ and sulfolane molecules, and the site of
      solvation is the oxygen atom of -SO2 group. The molecular orbital calculation
      supports this suggestion. On the other hand, the apparent solvation number was
      calculated, and the band fitting for the ClO4- band reveals the presence of
      contact ion pair, solvent separated ion pair and free ClO4- anion in the
      concentrated solutions.

PMID- 11471708
TI  - FT-Raman, FT-IR and surface enhanced Raman scattering spectra of sodium
      salicylate.
AB  - FT-IR and FT-Raman spectra of sodium salicylate were recorded and analysed.
      Surface enhanced Raman scattering (SERS) spectrum was recorded is silver colloid.
      Comparisons of the SERS spectrum with the spectra in solution and of the solid
      sample are made. Sodium salicylate (an O donor ligand) is thought to adsorb in a
      somewhat 'tilted side on orientation' with respect to the silver surface.

PMID- 11471709
TI  - Raman and infrared spectra, conformational stability, ab initio calculations and
      assignment of fundamentals for 1-bromo-3-fluoropropane.
AB  - The infrared and Raman spectrum of 1-bromo-3-fluoropropane is reported in the
      gas, liquid, amorphous solid and annealed polycrystalline states. Only one of the
      five possible conformers is stable in the crystal, designated the C conformer.
      The disordered phases show the presence of several other conformers of higher
      energy, due entirely to conformers designated B and D. Ab initio calculations
      were performed as rhf/4-31g*/MIDI-4*, rhf/6-31g* and mp2/6-31g* (both frozen core
      and full electron correlation) for all five conformers. The scaled harmonic force
      field obtained using the mp2 = full/6-31g* level of the theory is reported for
      the most stable conformer together with an assignment of fundamentals and
      potential energy distributions for local symmetry coordinates. Selected
      computational results are reported for all conformers together with scaled and
      unscaled wavenumbers and infrared and Raman intensities. The temperature
      dependent Raman spectrum is reported from room temperature to -100 degrees C.
      Only three of the five possible conformers can be identified in this spectrum,
      and there is no evidence of the other two. The energy differences between
      conformers in the liquid phase were found experimentally to be 132+/-27, 232+/-46
      and 106+/-30 cm(-1), respectively between the D and C, B and C and D and B
      conformers. These differences are substantially less than the differences
      calculated ab initio at the highest level of the theory used, suggesting that
      energy differences were decreased by large dipole-dipole interactions present in
      the liquid but not in the gas.

PMID- 11471710
TI  - Spectroscopic studies on molecular recognition capabilities of a nucleolipid
      bearing thymine headgroup to adenosine.
AB  - The Langmuir-Blodgett (LB) films of octadecanoyl ester of 1-(2-carboxyethyl)
      thymine deposited from pure water and aqueous adenosine subphases were
      investigated by ultraviolet-visible (UV-vis), Fourier transform infrared
      attenuated total reflection (FTIR-ATR), and Fourier transform surface-enhanced
      Raman scattering (FT-SERS) spectroscopy. The obtained spectral results indicate
      that the adenosine molecules in the subphase can be transferred onto solid
      substrates by LB techniques as a result of the formation of base pairs at the
      air/water interface. UV-vis spectra alternations indicated that, with increasing
      adenosine concentration in subphase, more adenosine molecules were recognized by
      nucleolipid monolayer and were transferred onto the quartz substrates. The closed
      packing of the constituent molecules facilitates the photodimerization of the
      thymine moieties in the headgroup under ultraviolet irradiation. FTIR-ATR results
      suggest that the hydrocarbon chains of nucleolipid in the LB films deposited from
      pure water and aqueous adenosine take on a close-packed all trans conformation.
      By analyzing the FT-SERS spectra results, it can be deduced that the orientation
      of nucleobase in the headgroup is different before and after the recognition
      effect occurred. For LB film deposited from pure water, the nucleobases are lying
      flat on the silver substrates; whereas for LB film deposited from aqueous
      adenosine, the base pairs take an end-on adsorption on silver substrate.

PMID- 11471711
TI  - Fluorometric study of the inclusion interaction of beta-cyclodextrin derivatives
      with tetraphenylporphyrin and its analytical application.
AB  - The effects of native beta-cyclodextrin (beta-CD) and four kinds of alkylated
      beta-cyclodextrin (beta-CDs), i.e. heptakis (2,6-di-O-isobutyl-beta-cyclodextrin)
      (I), heptakis (2,6-di-O-octyl-beta-cyclodextrin) (II), heptakis (2,6-di-O-dodecyl
      beta-cyclodextrin) (III), and heptakis (2,6-di-O-hexadecyl-beta-cyclodextrin)
      (IV), on the fluorescence behaviors of tetraphenylporphyrin (TPP) are
      investigated. An obvious fluorescence enhancement is observed from TPP by using
      alkylated derivatives compared to that obtained in beta-CD aqueous or in water. A
      114-N fluorescence emission intensity enhancement is found for the complex with
      2,6-di-O-octyl-beta-cyclodextrin relative to the free analyte. The exact
      stoichiometric ratios and the formation constants of the inclusion complexes have
      been examined by application of curve fitting method. The linear calibration
      plots between fluorescence intensity and TPP concentration are determined in the
      1.14 x 10(-8)-5.06 x 10(-6) mol l(-1) range.

PMID- 11471712
TI  - Absolute band intensities of acetone ((CH3)2CO) in the infrared region of 830
      3200 cm(-1) at low and room temperatures.
AB  - Absolute integrated band intensities of acetone (CH3)2CO in the region of 830
      3200 cm(-1) have been measured near the temperatures of 233, 260 and 293 K. The
      spectra were recorded with a Fourier transform infrared (FTIR) spectrometer. The
      investigated region encompasses a total of 15 fundamental bands. At 293 K, for
      example, the band intensities range from 16.8 to 554.3 cm(-2) atm(-1) (at 300 K).
      The intensities have uncertainties of about 5%. All the band intensities increase
      with decreasing temperature. An empirical formulation was introduced which fit
      this temperature dependence well and which can be used to predict other
      unmeasured band intensities in the temperature region of approximately 200-300 K.
      The 295 K intensities reported here agree to within approximately 10% of
      previously published values, with lower estimated uncertainties. Low temperature
      intensity measurements are not available in the literature.

PMID- 11471713
TI  - A spectroelectrochemical study of the reduction of a Schiff base cryptand.
AB  - The electrochemical reduction of a bicyclic hexaimino Schiff base cryptand 1
      (N[(CH2)2N-CH-meta-C6H4-CH=N(CH2)2]3N) and that of one of its strands 2 ((CH3)2CH
      N=CH-meta-C6H4-CH=N-CH(CH3)2) has been studied by visible and near infrared in
      situ spectroelectrochemical techniques. These results are in good agreement with
      those obtained using alkali metals, but in this case the effect of the formation
      of ion pairs is minimized through the use of tetrabutylammonium cations. It is
      confirmed that 1- and 1= have the same visible and near IR spectrum. The spectrum
      of the products of the electrochemical reduction of 2 is similar to those of 1-
      or 1=.

PMID- 11471714
TI  - Infrared spectra of 1 -monopalmitin- or 1-monostearin-water systems in the gel
      phase.
AB  - The infrared spectra of 1-monopalmitin- or 1-monostearin-water systems in the gel
      phase were observed at room temperature. In both systems the infrared intensities
      of the bands parallel and perpendicular to the paraffin chain are relatively
      reduced and enhanced, respectively, on going from the crystalline phase to the
      gel phase. These spectral changes are explained in terms of the interaction among
      oscillating dipoles, which is sensitive to the morphology change from the three
      dimensional crystalline phase to the two-dimensional lipid bilayers. The non
      planar lipid bilayers are proposed for the gel phase in monopalmitin-water
      systems with x > or = 35 (x: wt.% water).

PMID- 11471715
TI  - The vibrational spectra of [15N2]-succinonitrile.
AB  - For the first time, the infrared and Raman spectra of [15N2]-succinonitrile are
      presented and discussed in detail. Assignments of the vibrational bands of its
      two rotational conformers gauche and trans, respectively, have been made for both
      infrared and Raman spectra. The assignments were based on a recent ab-initio
      force field calculation for succinonitrile, taking into account the vibrational
      frequencies of other succinonitrile isotopomers. There are differences in the
      frequencies of the vibrational bands due to the mass increase in the cyanide
      groups, which have been analysed in depth.

PMID- 11471716
TI  - Infrared spectra of phthalic acid, the hydrogen phthalate ion, and the phthalate
      ion in aqueous solution.
AB  - The infrared spectra of a series of aqueous solutions containing phthalic acid
      (1,2-benzenedicarboxylic acid) and varying pH were examined using attenuated
      total reflection Fourier transform infrared spectroscopy and potentiometry. The
      basis spectra of phthalic acid, the hydrogen phthalate ion, and the phthalate ion
      were isolated using a factor analysis in which the absorbance of these species
      varies with pH and total phthalate concentration according to equilibrium and
      mass balance relations. Assignments of these basis spectra were made by
      comparison with spectra calculated ab initio. The conditional formation constants
      of phthalic acid and the hydrogen phthalate ion were determined at 25.0+/-0.1
      degrees C in 0.6 M NaCl ionic media using infrared spectroscopy and in 1.5 M NaCl
      ionic media using both infrared spectroscopy and potentiometry.

PMID- 11471717
TI  - Metal complexes of antibiotic drugs. Studies on dicluxacillin complexes of FeII,
      FeIII, CoII NiII and CuII.
AB  - The synthesis and characterization of dicluxacillin (DC) complexes with di- and
      tri-valent metal ions are described. The nature of bonding of the chelated DC and
      its metal complexes structures have been elucidated on the basis of their
      spectroscopic (infrared, solid reflectance, magnetic spectra, mass and thermal
      analysis) properties. In all the complexes studied, the DC acts as a chelate
      monoanionic ligand with coordination involving the carboxylate O atom and the
      endocyclic N of the thiazole ring. The DC ligand forms mono-ligand complexes of
      the general formula [M(DC)(H2O)x(A)]. yH2O where DC is the uninegatively charged
      bidentate ligand and A = OAc in case of CuII and Cl in case of FeIII, FeII, CoII
      and NiII ions. IR, solid reflectance spectra and magnetic moment measurement are
      used to infer the structure and to illustrate the coordinating capacity of the
      ligand. From the thermal decomposition curves, the water molecules of
      crystallization are removed in a single stage while the decomposition of the
      ligand and coordinated water molecules occur in the second and subsequent stages.
      Different thermodynamic kinetic parameters namely activation energy (E*),
      enthalpy of activation (AH*), entropy of activation (AS*) and free energy change
      of activation (AG*) are calculated using Coats and Redfern equation.

PMID- 11471718
TI  - Synthesis, spectroscopic characterization and ESR studies on electron transfer
      reactions of bis[N-(2,6-di-tert-butyl-1-hydroxyphenyl)salicylaldiminato]
      copper(II) complexes with PbO2 and PPh3.
AB  - New bis[N-(2,6-di-t-butyl-1-hydroxyphenyl)salicylideneminato]copper(II) complexes
      bearing HO and CH3O substituents on the salicyaldehyde moiety were prepared, and
      their spectroscopic properties, as well as redox reactivity towards PbO2 and
      PPh3, examined by ESR and UV spectroscopy. In the process of synthesis of HO
      complexes unlike CH3O the oxidative C-C coupling of coordinated salicylaldimine
      ligands does not takes place. The powder ESR spectra of CH3O substituted
      complexes unlike of HO analogues are typical of a triplet state Cu(II) dimers
      with a half-field forbidden (deltaM = +/- 2) transition and the allowed
      transitions (AM = +/- 1) dimeric form of the complexes at 300 and 113 K. The one
      electron oxidation of 3-CH3O and all of the OH complexes with PbO2 to give
      indophenoxyl type secondary radicals which are significantly different from those
      observed for analogues Cl, Br and NO2 substituted chelates. The presented
      complexes unlike their electron-withdrawing analogues are readily reduced by PPh3
      via intramolecular electron transfer from ligand to copper(II) to give various
      radical intermediates as well as Cu(I) radical ligand compounds. The analysis of
      ESR spectra all of the complexes and radical intermediates are presented.

PMID- 11471719
TI  - NMR study on the interaction of 1,4-cubanedicarboxylic acid and its esters with
      elemental fluorine. The synthesis of dimethyl 2-fluorocubane-1,4-dicarboxylate.
AB  - Elemental fluorine can be successfully used for fluorination of cubane
      derivatives. The nature of the products depends on the fluorination conditions:
      in CH3CN at -20 to -30 degrees C, dimethyl 2-fluorocubane-1,4-dicarboxylate was
      obtained from dimethyl ester of 1,4-cubanedicarboxylic acid; in CF3COOH at -12 to
      -15 degrees C in the presence of alkali metal acetates, 1,4-cubanedicarboxylic
      acid and its dimethyl and diethyl esters gave complex mixtures of fluorinated
      cubane products. Our investigation by 1H and 19F NMR spectroscopy and spectra
      computer simulation revealed production of mono- and difluorinated cubanes.
      Fluorine-containing cubane derivatives were also found with extra substituents in
      other than 1 and 4 positions.

PMID- 11471720
TI  - Vibrational study and fluorescence bands in the FT-Raman spectra of Ca(10
      x)Pb(x)(PO4)6(OH)2 compounds.
AB  - About 40 apatitic compounds, stoichiometric or not, with different substitutions
      like lead, sodium and cadmium were investigated using infrared, Raman and FT
      Raman spectroscopies. In the Ca(10-x)Pb(x)(PO4)6(OH)2 sequence (x runs from 0 to
      10), the evolution of the fluorescence bands observed by FT-Raman, only with
      stoichiometric entities apatites, is mainly regarded and explained. Important
      spectral changes concerning the OH- and the PO4(3-) entities occur when 4 < or =
      x < or = 7. The intensity ratio of the two components of the v1 PO4(3-) mode is
      shown to be a suitable method to determine the lead content. The weak OH...O
      hydrogen bonds involving the OH- ions, of which the disorder is discussed, are
      different for the lead and calcium hydroxyapatites. The evolution of the
      fluorescence bands, as well as the splitting of the v(OH) mode, are due to the
      lead distribution in the two sites, with a preference for sites II, of the
      hydroxyapatite structure. The effect of temperature is also reported.

PMID- 11471721
TI  - Stereochemistry of new nitrogen containing heterocyclic aldehyde. VI. Novel
      structural and properties models of uranyl with quinoline azodyes.
AB  - A novel series of UO2(2+) complexes with 5-(4'-derivatives phenyldiazo)-8-hydroxy
      7-quinolinecarboxaldehyde (L1H-L7H), have been prepared. The composition and
      structure were confirmed by elemental analyses, 'HNMR spectra and IR spectroscopy
      measurements. Data from the above show that they exist in two isomeric solid
      forms. The polymeric structure results from intermolecular U=O...U=O
      interactions. The ligands act as a monobasic bidentate chelating agent
      coordinating through C=O and OH groups by replacement of a proton from the latter
      group. The force constant F(U-O) (mdyn A(-1)) and the bond length R(U-O) (A) of
      the U-O bond were calculated from the IR data and related to the electronic
      properties of the substituents. The existing literature on the coordination
      chemistry of these ligands are obscure.

PMID- 11471722
TI  - A new approach to determining the geometry of weakly coupled radical pairs from
      their electron spin polarization patterns.
AB  - Analytical expressions for the spin polarized EPR lineshapes of weakly coupled
      radical pairs (RPs) are derived as functions of the angles between the
      anisotropic g-tensors of the radicals and the vector describing the dipolar
      coupling. It is shown that with a singlet precursor the EPR signal of the RP can
      be written as a linear function of the dipolar coupling. Under these conditions,
      the calculated powder spectrum can be expressed as a linear combination of four
      powder spectra, which are independent of the geometry of the RP. To reproduce the
      experimental spectra the optimal set of coefficients can be found by least
      squares fitting. The advantage of this approach is that the four powder spectra
      must only be calculated once. This treatment shows very clearly the restrictions
      placed on the information obtainable from such spectra. Most importantly, a
      unique set of angles can only be obtained if the absolute amplitude of the
      spectrum is known. In general, the calculated spectrum is related to the
      experimental spectrum by an unknown, arbitrary scaling factor. In this case, sets
      of angles consistent with the data are obtained. Possible strategies for
      obtaining unique geometric information are discussed and demonstrated with the
      experimental data for the state P+*(865)Q-*(A) in Zn-substituted bacterial
      reaction centres.

PMID- 11471723
TI  - NMR evidence for Mg(II) binding to N1 of ATP.
AB  - The conformation of the complex of [ATP-Mg]2+ is studied by 1H, 15N and 31P NMR
      on ATP in the absence and presence of MgCl2 in a wide pH range from 1 to 10. 1H
      15N HMBC experiments show a large change in the 15N chemical shift of N1 up to 10
      ppm around pH 3.7, suggesting that there is a strong interaction between Mg2+ and
      N1 of ATP at this pH. 31P NMR indicates that at pH 3.7 the phosphate chain also
      binds Mg2+. 1H diffusion measurements imply that the [ATP-Mg]2+ complex involves
      only one ligand and one metal ion.

PMID- 11471724
TI  - Cytokinin-induced gene expression in cultured green cells of Nicotiana tabacum
      identified by fluorescent differential display.
AB  - The cell growth and plastid development of cultured green tobacco cells were
      maintained by the phytohormone cytokinin. After subculture into cytokinin-free
      medium, when cytokinin treatment was resumed, physiological changes induced by
      cytokinin were analyzed. Changes in chlorophyll biosynthesis and photosynthetic
      gene expression were observed 1 week after cytokinin induction, and changes in
      cell growth were observed 2 weeks after cytokinin induction. Two cytokinin
      induced genes (cig) were isolated from these cells using the fluorescent
      differential display technique. Northern analysis confirmed that expression of
      these cig was induced by both natural and synthetic cytokinins. The expression of
      cig1 was also induced by abscisic acid, and its cDNA sequence was similar to the
      proline dehydrogenase gene. The expression of cig2 is specific to cytokinin and
      is not induced by other phytohormones. The amino acid sequence encoded by cig2 is
      similar to the GDP/GTP exchange factor eIF2B, which regulates translation
      initiation. The expression of these cig suggests a complex induction system
      involving cytokinin and other phytohormones.

PMID- 11471725
TI  - Conjugation of Arg-Gly-Asp (RGD) sequence in copolymer bearing sugar moiety for
      insulinoma cell line (MIN6) culture.
AB  - Copolymers composed of an Arg-Gly-Asp (RGD) sequence for the adhesion molecule
      and sugar moieties were synthesized for an insulinoma cell (MIN6) culture. MIN6
      cells attached on the poly(N-p-vinylbenzyl-D-maltonamide-co-6-(p-vinylbenzamido)
      hexanoic acid-g-GRGDS) (p(VMA-co-VBGRGDS))-coated dishes were in a more
      aggregated form than other polymer-coated surfaces. P(VMA-co-VBGRGDS) also shows
      faster proliferation of MIN6 cells (about 18% higher) than with p(VLA-co
      VBGRGDS). By interaction between cell and matrix, about 80% greater insulin
      secretion from MIN6 cells was produced with the p(VMA-co-VBGRGDS), and about 50%
      greater insulin secretion was produced with the poly(N-p-vinylbenzyl-D
      lactonamide-co-6-(p-vinylbenzamido)-hexanoic acid-g-GRGDS) (p(VLA-co-VBGRGDS) as
      compared with unstimulated cells. Moreover, attachment of MIN6 cells treated with
      RGD monomer was suppressed approximately 50% for the p(VMA-co-VBGRGDS) surface.
      This result supported the idea that conjugation of adhesion molecules of RGD
      peptide in p(VMA-co-VBGRGDS) copolymer specifically interact with integrin
      families on MIN6 cell membrane.

PMID- 11471726
TI  - Purification and characterization of an oligo-isomaltosaccharide synthase from a
      Streptococcus sobrinus glucosyltransferase-I deficient mutant.
AB  - One glucosyltransferase (GTF) -I deficient mutant of Streptococcus sobrinus
      strain B13N was isolated through chemical mutagenesis with ethyl
      methanesulfonate, and characterized. This mutant, designated as B13N-Id, readily
      allowed us to purify a homogeneous oligo-isomaltosaccharide synthase (GTF-S) from
      its culture fluid. The purified GTF-S was only recognized with rabbit polyclonal
      antibody against recombinant GTF-S from an Ecsherichia coli MD124 clone
      expressing the B13N gtfS gene, and showed the almost same enzymatic properties as
      the recombinant enzyme. A double reciprocal plot of the B13N GTF-S for sucrose
      was biphasic, and the affinity for this substrate was high compared to that of
      GTF-S enzymes from other strains.

PMID- 11471727
TI  - Growth promotion of rice seedlings by allelopathic polysaccharide from Welsh
      onion.
AB  - The underground portion of the Welsh onion (Allium fistulosum) was extracted and
      separated into seven fractions to purify allelopathic compounds that were found
      to promote the growth of rice seedlings (Oryza sativa). The 80% (v/v) ethanol
      insoluble fraction of the hot water extract showed the highest growth-promoting
      effect. Purification by DEAE-cellulose chromatography gave four fractions, AD-1,
      2, 3 and 4. AD-3 at 1000 ppm stimulated root and shoot growth by about 2.4 and
      1.5 times over the respective water and sucrose-treated controls. The molecular
      weight of AD-3 was roughly estimated as 630 kDa by gel permeation chromatography.
      Seventy two percent (by wt.) of AD-3 was a carbohydrate and no proteins were
      detected. A GC analysis of the neutral sugar composition revealed the presence of
      Gal (50.1%), Man (17.9%), Ara (10.4%), Rha (8.8%), Glc (7.2%) and Xyl (5.6%).
      About 3% (by wt.) of the total carbohydrate was uronic acid, which was identified
      as GalU by a GC analysis. The remainder of AD-3 was extracted in ethyl acetate
      after its hydrolysis with 2 M HCl. The major component of the ethyl acetate
      soluble fraction was identified as unsaturated linear primary alcohols, 1
      tetradecanol and 1-octadecanol (16% and 84% by peak areas from GC, respectively)
      by means of NMR and GC-MS. Sole or combined treatment of these alcohols did not
      affect the growth of rice seedlings. After partial hydrolysis with 0.2 M
      trifluoroacetic acid or by a sodium periodate treatment, the activity of AD-3 had
      completely disappeared, suggesting that the sugar moiety and/or molecular size
      were important for the activity.

PMID- 11471728
TI  - Isolation and antioxidant activity of galloyl flavonol glycosides from the
      seashore plant, Pemphis acidula.
AB  - Four kinds of galloyl flavonol glycosides were found in the leaf extract of
      Pemphis acidula, a plant growing on the subtropical seashore. Their chemical
      structures were elucidated to be quercetin or kaempferol 6"-O-galloyl-beta-D
      glycosides by using spectroscopic and chemical analyses. One of the flavonols,
      kaempferol-3-O-(6-O-galloyl-beta-D-galactopyranoside), was newly isolated from
      natural sources and its structure was completely determined in this
      investigation. The antioxidant-related activities of the galloyl flavonoids were
      examined by the DPPH antiradical activity, inhibition of methyl linoleate
      oxidation, and inhibition of oxidative cell death. These results were compared
      with those of the corresponding non-galloylated flavonol glycosides and their
      aglycones. The galloyl flavonoids showed more efficient activity than that of the
      corresponding flavonol glycosides, but not more than that of the corresponding
      aglycones in the three assays applied.

PMID- 11471729
TI  - Characterization of recombinant yeast exo-beta-1,3-glucanase (Exg 1p) expressed
      in Escherichia coli cells.
AB  - Yeast exo-beta-1,3-glucanase gene (EXG1) was expressed in Escherichia coli and
      the recombinant enzyme (Exg1p) was characterized. The recombinant Exglp had an
      apparent molecular mass of 45 kDa by SDS-PAGE and the enzyme has a broad
      specificity for beta-1,3-linkages as well as beta-1,6-linkages, and also for
      other beta-glucosidic linked substrates, such as cellobiose and pNPG. Kinetic
      analyses indicate that the enzyme prefers small substrates such as laminaribiose,
      gentiobiose, and pNPG rather than polysaccharide substrates, such as laminaran or
      pustulan. With a high concentration of laminaribiose, the enzyme catalyzed
      transglucosidation forming laminarioligosaccharides. The enzyme was strongly
      inhibited with high concentrations of laminaran.

PMID- 11471730
TI  - Copper staining method for extracting biologically active proteins from native
      gels.
AB  - An attempt was made to make protein bands visible on native gel using copper
      staining, since such a mild staining procedure would make the entire native gel
      electrophoresis process non-denaturing. Copper staining not only was able to
      detect various proteins on native gel with reasonable sensitivity, but also made
      extraction and recovery of active proteins possible from the gel using a gentle
      procedure.

PMID- 11471731
TI  - Kinetic and thermodynamic analysis of thermal unfolding of recombinant
      erythropoietin.
AB  - Thermal stress was used to assess the stability of recombinant human
      erythropoietin (EPO) derived from Chinese hamster ovary cells. In 20 mm phosphate
      at pH 7.0, this protein had a highly reversible thermal unfolding as observed by
      far UV circular dichroism (CD) and native gel analysis, with no indication of
      protein aggregation. It had a relatively low melting temperature at 53 degrees C.
      Assuming a two-state transition, the observed reversibility permits thermodynamic
      analysis of the unfolding of EPO, which shows that the free energy of unfolding
      at 25 degrees C is only 6-7 kcal/mol. Upon heating to 79 degrees C over 30 min,
      however, this protein does undergo aggregation as assessed by native gel. In 20
      mm phosphate and citrate at pH 7.0, the results are similar, i.e., EPO suffered a
      substantial aggregation, while it showed little aggregation in 20 mm Tris or
      histidine at pH 7.0 and 20 mm glycine at pH 6.3 under identical heat treatment.

PMID- 11471732
TI  - A novel rhamnose-binding lectin family from eggs of steelhead trout (Oncorhynchus
      mykiss) with different structures and tissue distribution.
AB  - An L-rhamnose-binding isolectin named STL3 (subunit Mr, 21.5 k) was isolated from
      eggs of the steelhead trout (Oncorhynchus mykiss) in addition to STL1 (subunit
      Mr, 31.4 k) and STL2 (subunit Mr, 21.3 k) that had been already isolated. STLs
      were composed of noncovalently linked subunits. The primary structures of STL1
      and STL3 were analyzed by the combined use of protein sequencing and cDNA
      sequencing. A cDNA encoding STL2, of which the protein sequence had been
      previously studied, was also analyzed. The STL1 subunit (289 amino acid residues)
      had different structural properties compared to those of the STL2 subunit (195
      amino acid residues) and the STL3 subunit (195 amino acid residues); e.g., the
      number of repeated domain (three for STL1, and two for STL2 and STL3), although
      all of them were composed of tandemly repeated homologous domains (40 to 53%
      identities). The lectin levels in various tissues and during the embryonic
      development showed that STL1 had different distribution and expression profiles
      from those of STL2 and STL3. Although STL1 could be detected in several tissues
      and serum of both male and female steelhead trout, STL2 and STL3 were only
      abundant in the ovary. STL2 and STL3 levels dramatically decreased just after
      hatching, however, the STL1 level increased temporarily. These results indicate
      that the multiple lectins from eggs of the steelhead trout form a novel rhamnose
      binding lectin family with different structures and tissue distribution to share
      distinct functions in eggs.

PMID- 11471733
TI  - Effects of dietary pyrazinamide, an antituberculosis agent, on the metabolism of
      tryptophan to niacin and of tryptophan to serotonin in rats.
AB  - The effects of pyrazinamide on the metabolism of tryptophan to niacin and of
      tryptophan to serotonin were investigated to elucidate the mechanism for
      pyrazinamide action against tuberculosis. Weanling rats were fed with a diet with
      or without 0.25% pyrazinamide for 61 days. Urine samples were periodically
      collected for measuring the tryptophan metabolites. The administration of
      pyrazinamide significantly increased the metabolites, 3-hydroxyanthranilic acid
      and beyond, especially quinolinic acid, nicotinamide, N'-methylnicotinamide, and
      N1-methyl-4-pyridone-3-carboxamide, and therefore significantly increased the
      conversion ratio of tryptophan to niacin and the blood NAD level . However, no
      difference in the upper metabolites of the tryptophan to niacin pathway such as
      anthranilic acid, kynurenic acid and xanthurenic acid was apparent between the
      two groups. No difference in the concentrations of trytptophan and serotonin in
      the blood were apparent either. It is suggested from these results that the
      action of pyrazinamide against tuberculosis is linked to the increase in turnover
      of NAD and to the increased content of NAD in the host cells.

PMID- 11471734
TI  - Calcium ions stabilize a protein structure of hemolytic lectin CEL-III from
      marine invertebrate Cucumaria echinata.
AB  - CEL-III, a galactose/N-acetylgalactosamine (Gal/GalNAc)-specific lectin purified
      from a marine invertebrate, Cucumaria echinata, has a strong hemolytic activity,
      especially toward human and rabbit erythrocytes in the presence of Ca2+. We
      evaluated the role of Ca2+ in hemagglutinating and hemolytic activities of CEL
      III. We found that Ca2+ is closely associated with both activities of CEL-III.
      The fluorescence spectra of CEL-III upon binding to Ca2+ were measured. The
      result showed a structural change of CEL-III in the presence of Ca2+. The
      structural change of CEL-III upon Ca2+ binding was further demonstrated by
      stabilization against urea denaturation and by insusceptibility to protease
      digestions. CEL-III was completely unfolded at a low concentration of 2 M urea,
      while CEL-III complexed with Ca2+ was stable in 6 M urea. As for protease
      digestions, CEL-III monomer and oligomer were readily digested by trypsin,
      chymotrypsin, and papain in the absence of Ca2+, while they were insusceptible to
      the three proteases in the presence of Ca2+. The papain digestion of the
      decalcified oligomer produced a large C-terminal peptide, suggestting that the C
      terminal region of CEL-III may participate in oligomerization of CEL-III as a
      core domain.

PMID- 11471735
TI  - Milk basic protein promotes bone formation and suppresses bone resorption in
      healthy adult men.
AB  - Milk contains several components effective for bone health. In the previous in
      vitro and in vivo studies, we have shown that milk whey protein, especially its
      basic protein fraction (milk basic protein [MBP]), promoted bone formation and
      suppressed bone resorption. This present study examines the effect of MBP on the
      biochemical markers of bone metabolism in healthy adult men. Experimental
      beverages containing MBP (300 mg of MBP a day) were given to 30 normal healthy
      adult men for 16 days. The serum osteocalcin concentration had increased
      significantly after 16 days of ingesting the experimental beverage containing
      MBP. Urinary cross-linked N-teleopeptides of type-I collagen (NTx) excretion had
      decreased significantly after 16 days of ingesting MBP. The urinary NTx excretion
      was related to the serum osteocalcin concentration after 16 days of ingestion.
      These results suggest that MBP promoted bone formation and suppressed bone
      resorption, while maintaining the balance of bone remodeling.

PMID- 11471736
TI  - New allyl ester linker and solid-phase block synthesis of the serglycin core
      region.
AB  - The prototype glycopeptidyl fragments of serglycin, a proteoglycan with the
      characteristic peptide sequence of repeating L-seryl-L-glycine, were synthesized
      by a convergent method involving block condensation on a solid support. In order
      to facilitate detachment of the protected glycopeptides from the resin, a new
      allyl ester type of linker, which is cleavable by Pd(O)-catalysis, was designed
      and used in combination with the commercial acid-labile Sieber amide resin for
      the solid-phase synthesis. Glycopeptide blocks consisting of [O-(2,3,4-tri-O
      acetyl-D-xylosyl)-L-seryl-L-glycine]n (n = 1 - 8) were produced in good yields.
      Block condensation in a solution was also successful to synthesize up to the
      hexadecapeptide (n = 8).

PMID- 11471737
TI  - Glucosylceramide synthesis inhibitors block pharmacologically induced dispersal
      of the Golgi and anterograde membrane flow from the endoplasmic reticulum:
      implication of sphingolipid metabolism in maintenance of the Golgi architecture
      and anterograde membrane flow.
AB  - PDMP (D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) and PPMP (D,L
      threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol), inhibitors of
      glucosylceramide synthesis, blocked brefeldin A (BFA)- and nordihydroguaiaretic
      acid-induced dispersal of the Golgi and trans Golgi network, and Golgi-derived
      vesicles were retained in the juxtanuclear region. PDMP and PPMP did not
      stabilize microtubules but blocked nocodazole-induced extensive fragmentation and
      dispersal of the Golgi, and large Golgi vesicles were retained in the
      juxtanuclear region. PPMP is a stronger inhibitor of glucosylceramide synthesis
      than PDMP, but PDMP showed a stronger activity against BFA-induced retrograde
      membrane flow. However, PPMP showed a stronger activity for Golgi disruption and
      inhibition of anterograde trafficking from the endoplasmic reticulum, and
      rebuilding of the Golgi architecture. Cumulatively, these results suggest that
      sphingolipid metabolism is implicated in maintenance of the Golgi architecture
      and anterograde membrane flow from the endoplasmic reticulum but not in Golgi
      dispersal induced by BFA.

PMID- 11471738
TI  - Molecular cloning of groESL locus, and purification and characterization of
      chaperonins, GroEL and GroES, from Bacillus brevis.
AB  - The groESL locus of a protein-hypersecreting bacterium, Bacillus brevis, was
      cloned by PCR using primers designed based on the DNA sequence of a B. subtilis
      homolog. GroEL protein was purified to apparent homogeneity and its ATPase
      activity was characterized: it hydrolyzed ATP, CTP, and TTP in this order of
      reaction rate, and its specific activity for ATP was 0.1 micromole/min/mg
      protein. Purified GroEL forms a tetradecamer. GroEL was estimated to contain 22%
      alpha-helix, 24% beta-sheet, and 19% turn structures, by CD measurement. GroES
      protein was also highly purified to examine its chaperonin activity. GroEL
      protected from thermal inactivation of and showed refolding-promoting activity
      for malate dehydrogenase, strictly depending on the presence of ATP and GroES.

PMID- 11471739
TI  - Coupling of fermentation and esterification: microbial esterification of decanoic
      acid with ethanol produced via fermentation.
AB  - Two different kinds of bioprocess, ethanol fermentation and subsequent microbial
      esterification, were coupled using Issatchenkia terricola IFO 0933 in an
      interface bioreactor. The strain produced ethyl decanoate (Et-DA) by
      esterification of exogenous decanoic acid (DA) with ethanol produced via
      fermentation. The efficiency of the new coupling system depended on the
      concentration of glucose in a carrier and DA in an organic phase (decane) in an
      agar plate interface bioreactor. Optimum glucose content and DA concentration
      were 4% and 29 mM, respectively.

PMID- 11471740
TI  - Characterization of aspartate kinase III of Bacillus subtilis.
AB  - A search in the Bacillus subtilis genome sequence found that the gene designated
      yclM encode(s) a protein showing significant identity in amino acid sequence to
      aspartate kinases. When yclM was introduced into Escherichia coli cells deficient
      in all three aspartate kinase genes, production of a protein with molecular size
      50 kDa, which was similar to the value deduced from the nucleotide sequence of
      the gene, was observed. Expectedly, the protein purified to homogeneity had
      aspartate kinase activity. The enzyme was significantly inhibited by simultaneous
      addition of both threonine and lysine, which is a typical feature of aspartate
      kinase III of B. subtilis. The enzyme was very unstable in 10 mM tris-HCl (pH
      7.5) buffer, but was stabilized by addition of 500 mM ammonium sulfate. Although
      all the aspartate kinases so far investigated are oligomeric enzymes, this
      aspartate kinase was suggested to be a monomer.

PMID- 11471741
TI  - Four polyoxygenated cyclohexenes from the Chinese tree, Uvaria purpurea.
AB  - Two novel polyoxygenated cyclohexenes, 6-methoxyzeylenol (3) and 2
      acetoxyzeylenone (4), together with two known compounds, zeylenol (1) and
      zeylenone (2), were isolated from the heartwood of the Chinese tree, Uvaria
      purpurea. Zeylenol (1) and zeylenone (2) both showed inhibitory activity toward
      the root growth of Lactuca sativa. Their structures were established by
      spectroscopic and chemical methods.

PMID- 11471742
TI  - Properties of an extracellular polysaccharide produced by a strain of
      enterobacter isolated from pond water.
AB  - A bacterium which was isolated from pond water and identified as Enterobacter
      cloacae produced a viscous extracellular polysaccharide when it was grown
      aerobically in a medium containing sucrose as a sole source of carbon. The
      maximum molecular weight of the polysaccharide was about 9.0 x 10(5). The
      polysaccharide was composed of fucose, galactose, glucose, and glucuronic acid in
      a molar ratio of 2:3:2:1, but the molecular weight and the molar ratio of the
      sugar component were different from those of the polysaccharide produced by the
      same species reported elsewhere.

PMID- 11471743
TI  - Mulberry moracins: scavengers of UV stress-generated free radicals.
AB  - Mulberry leaves treated with UV-C were found to accumulate three different
      phytoalexins, moracin C, moracin N, and chalcomoracin. The increased level of
      malondialdehyde in UV-treated leaves along with moracins suggested their role as
      a free-radical scavenger in stressed plants. All the three moracins induced under
      UV stress were capable of scavenging the superoxide anion generated by the
      xanthine-xanthine oxidase system. Also, moracins were capable of inhibiting lipid
      peroxidation, which strongly indicates their role as a scavenger.

PMID- 11471744
TI  - Molecular cloning and characterization of cel2 from the fungus Cochlibolus
      carbonum.
AB  - A new cellulase gene, cel2, from the filamentous fungus Cochliobolus carbonum was
      cloned by using egl-1 of Trichoderma reesei as a heterologous probe. DNA blot
      analysis of cel2 showed that this gene is present as a single copy. The gene
      contains one 49-bp- intron. cel2 encodes a predicted protein (Cel2p) of 423 amino
      acids with a molecular mass of 45.8 kDa. The predicted pI is 4.96. It shows
      similarity to other endoglucanases from various fungi. From the comparison with
      other cellulase genes, cel2 belongs to family 7 of glucohydrolases. cel2 is
      located on a 2.5-Mb chromosome in C. carbonum and its expression is repressed by
      sucrose. A cel2 mutant of C. carbonum was created by transformation-mediated gene
      disruption. The pathogenicity of the mutant was indistinguishable from the wild
      type, indicating that cel2 by itself is not important for pathogenicity.

PMID- 11471745
TI  - Stronger suppression of plasma cholesterol and enhancement of the fecal excretion
      of steroids by a buckwheat protein product than by a soy protein isolate in rats
      fed on a cholesterol-free diet.
AB  - We investigated the effects of a buckwheat protein product (BWP), soy protein
      isolate (SPI) and casein on the plasma cholesterol level and fecal steroid
      excretion in rats fed on a cholesterol-free diet. The consumption of BWP
      suppressed plasma cholesterol by enhancing the fecal excretion of both neutral
      and acidic steroids. These effects of BWP were stronger than those of SPI.

PMID- 11471746
TI  - Effect of dietary histidine content on the change in content of skin urocanic
      acid isomers in hairless mice irradiated with ultraviolet B.
AB  - Hairless mice were fed with a 10% amino acid mixture diet (control diet, 0.42%
      histidine content), the control diet without histidine (histidine-free diet), or
      the control diet rich in histidine (histidine-rich diet; histidine content, 4.2%)
      for 32 days. They were irradiated with UV light of 312 nm for 30 min, and skin
      samples were periodically taken for measuring the urocanic acid isomers. Total
      urocanic acid isomers were decreased by UV irradiation in all the three groups,
      the recovery being the fastest in the histidine-rich group. The percentage
      increase in cis-urocanic acid/total urocanic acid was quickly increased by UVB
      irradiation. The recovery of the ratio was slightly higher in the histidine-rich
      group, although the total urocanic acid level was higher in the histidine-rich
      group than in the others. Therefore, the absolute cis-urocanic acid content in
      the skin was almost the same among the three groups. These results indicate that
      the increased histidine intake strengthened UVB protection without any decrease
      in immune suppression.

PMID- 11471747
TI  - Trehalose-producing operon treYZ from Arthrobacter ramosus S34.
AB  - Arthrobacter ramosus S34, which produces trehalose from maltooligosaccharide, was
      isolated. A trehalose-producing operon, treYZ, was cloned from the genome.
      Expression experiments with treY and treZ confirmed that they coded malto
      oligosyltrehalose synthase and malto-oligosyltrehalose trehalohydrolase,
      respectively. The amino acid sequence of TreY from A. ramosus S34 and that from
      Arthrobacter sp. Q36 did not show high identity, nor did those of TreZ.

PMID- 11471748
TI  - Cloning and expression of CitPDS1, a gene encoding phytoene desaturase in citrus.
AB  - A cDNA clone encoding phytoene desaturase (PDS) was isolated from citrus (Citrus
      unshiu Marc.). The transcript of the isolated PDS (CitPDS1) was not detected by
      conventional RNA gel-blot analysis; instead, it was detected by a sensitive
      reverse transcription-PCR (RT-PCR). The CitPDS1 transcript in the juice
      sacs/segment epidermis (edible part) was at a low level in the young fruit, and
      it increased toward maturation like citrus phytoene synthase (CitPSY1). In the
      peel, in contrast to CitPSY1, the transcript of which was induced toward
      maturation, the level of the CitPDS1 transcript remained constant after an
      increase in July, indicating non-coordinate regulation of CitPDS1 and CitPSY1 in
      the peel.

PMID- 11471749
TI  - New synthesis of serricornin, the female sex pheromone of the cigarette beetle.
AB  - Serricornin [(4S,6S,7S)-7-hydroxy-4,6-dimethyl-3-nonanonel, the female sex
      pheromone of Lasioderma serricorne, was synthesized by starting from (2S,4S)-2,4
      dimethyl-1,5-pentanediol that had been obtained by lipase-catalyzed enantiomer
      separation of its racemate.

PMID- 11471750
TI  - Antifeedants against Acusta despesta from the Japanese cedar, Cryptomeria
      japonica II.
AB  - Cryptomeria japonica against Acusta despesta. This hexane soluble-fraction was
      used to isolate and identify two sesquiterpenols, (-)-cubebol and (+)-2,7(14),10
      bisabolatrien-1-ol-4-one, as the active compounds. Both compounds strongly
      inhibited the feeding behavior of A. despesta at 120 microg/cm2 and 80 microg/cm2
      concentrations, respectively.

PMID- 11471751
TI  - Occurrence of the major food allergen, ovomucoid, in human breast milk as an
      immune complex.
AB  - The major food allergen, ovomucoid (molecular weight of 28 kDa) could be detected
      in 12 of 37 human breast milk samples by using three types of enzyme-linked
      immunosorbent assay. By gel-filtration, ovomucoid in breast milk was only eluted
      in the fractions corresponding to a molecular weight of about 450 kDa, suggesting
      its occurrence as an immune complex with IgA. In fact, almost the same elution
      profile as that for ovomucoid was obtained for its immune complex with IgA by gel
      filtration.

PMID- 11471752
TI  - Inhibitory effect of monoacylglycerol on fatty acid uptake into rat intestinal
      epithelial cells.
AB  - We investigated the influence of glycerol esters on oleic acid uptake into IEC-6
      cells. Monoolein, especially 2-monoacylglycerol, significantly inhibited the
      cellular uptake. Although diolein slightly inhibited the oleic acid uptake,
      triolein, glycerol and monooctanoate had no effect. These results suggest that
      after lipid digestion in the intestine, long-chain fatty acid uptake may be
      influenced by another digestive product, 2-monoacylglycerol.

PMID- 11471753
TI  - Oxidation of bisphenol A and related compounds.
AB  - Bisphenol A was oxidized to monoquinone and bisquinone derivatives by Fremy's
      salt, a radical oxidant, though salcomine and alkali did not catalyze the
      oxidation by molecular oxygen. Bisphenol A, bisphenol B, and 3,4'-(1
      methylethylidene)bisphenol were converted to their monoquinone derivatives in the
      presence of tyrosinase at 25 degrees C at pH 6.5, but not to the bisquinone
      derivatives under these conditions.

PMID- 11471754
TI  - Molecular mechanisms of self-incompatibility in Brassica.
AB  - In Brassica species, self-incompatibility has been mapped genetically to a single
      chromosomal location. In this region several closely linked genes have been
      identified. One of them, S-locus receptor kinase (SRK), determines S haplotype
      specificity of the stigma and it's the key protein for SI reaction. The role of
      the S locus glycoprotein (SLG) gene remains unclear. In the last decade
      approximately 15 additional genes linked to S-locus have been found. Recently, a
      gene has been identified (SCR) that encodes a small cysteine-rich protein which
      is a candidate for the pollen ligand. In addition to S locus linked genes there
      are unlinked SLRgenes (S-locus related genes). In this review, we discuss the
      role of these genes and the current view on the self-incompatibility mechanism in
      Brassica.

PMID- 11471755
TI  - Ribozyme pharmacokinetic screening for predicting pharmacodynamic dosing
      regimens.
AB  - A significant amount of research has been devoted to the chemical stabilization
      of synthetic ribozymes, in part, so that applications to systemic disease can be
      explored. A nuclease-stabilized synthetic hammerhead ribozyme, ANGIOZYME, has
      been developed which targets the mRNA encoding a vascular endothelial growth
      factor receptor, Flt-1. Because the stimulation of this receptor may contribute
      to tumor neovascularization and subsequent tumor growth and metastasis, we have
      explored the systemic use of ANGIOZYME to down regulate this receptor in a
      syngeneic model of metastatic cancer. We describe here the application of
      pharmacokinetic analysis to the selection of a dosing regimen for pharmacodynamic
      screening in this murine cancer model. These studies demonstrate that the
      appropriate application of pharmacokinetic analysis is necessary for the
      optimization of systemic pharmacodynamic studies using synthetic ribozymes.

PMID- 11471756
TI  - Biological membrane structure by solid-state NMR.
AB  - Nuclear magnetic resonance (NMR) spectroscopy, and particularly solid-state NMR
      spectroscopy, is a method of choice to study the structure and dynamics of both
      the lipid and the protein components of model and biological membranes. Different
      approaches have been developed to study these systems in which the restricted
      molecular motions result in broad NMR spectra. This contribution will first
      present an overview of the different techniques used to study lipid bilayers,
      namely 31p, 2H and 13C solid-state NMR spectroscopy. On the other hand, the study
      of the structure of membrane peptides and proteins is a rapidly growing field and
      several methods developed in the last two decades will be presented. These
      methods allow the investigation of protein systems for which structural
      information is often difficult to obtain by techniques such as X-ray diffraction
      and multidimensional solution NMR.

PMID- 11471757
TI  - Nitrogen fixation in methanogens: the archaeal perspective.
AB  - The methanogenic Archaea bring a broadened perspective to the field of nitrogen
      fixation. Biochemical and genetic studies show that nitrogen fixation in Archaea
      is evolutionarily related to nitrogen fixation in Bacteria and operates by the
      same fundamental mechanism. At least six nif genes present in Bacteria (nif H, D,
      K, E, N and X) are also found in the diazotrophic methanogens. Most nitrogenases
      in methanogens are probably of the molybdenum type. However, differences exist in
      gene organization and regulation. All six known nif genes of methanogens, plus
      two homologues of the bacterial nitrogen sensor-regulator glnB, occur in a single
      operon in Methanococcus maripaludis. nif gene transcription in methanogens is
      regulated by what appears to be a classical prokaryotic repression mechanism. At
      least one aspect of regulation, post-transcriptional ammonia switch-off, involves
      novel members of the glnB family. Phylogenetic analysis suggests that nitrogen
      fixation may have originated in a common ancestor of the Bacteria and the
      Archaea.

PMID- 11471758
TI  - Topics in migraine management: a survey of headache specialists highlights some
      controversies.
AB  - The authors' Survey of headache specialists highlights a number of controversial
      issues in migraine management including the following: acute treatment, focusing
      on use of triptans, and preventative medications; treatment of migraine with
      prolonged aura and basilar migraine; and the use of oral contraceptives in
      migraine. Interestingly, the prevalence of migraine among the headache
      specialists themselves is much higher than in the general population. Although
      triptans have revolutionized the acute treatment of migraine, treatment is still
      problematic for the sizable percentages of patients with an incomplete or no
      response and recurrence of headache. Triptans are generally very safe when the
      physician, aware of the potential for coronary artery vasoconstriction,
      appropriately screens patients before and during their use. Serotonin syndrome as
      a complication of triptan use is quite rare. Although there is no definite
      evidence of teratogenesis, triptans should not be taken during pregnancy unless
      the potential benefit justifies the potential risk to the fetus. Caution is also
      advised when using a triptan during breastfeeding. The United States Headache
      Consortium parameters, which consider indications for preventative treatment and
      propose general principles of management, are reviewed. Unfortunately, the
      experience of many migraineurs with preventative medications is less than
      satisfactory because of side effects or lack of efficacy. Treatment of both
      migraine with prolonged aura and basilar migraine is anecdotally based. Many
      headache specialists do not use beta blockers for prevention for those with
      prolonged aura and basilar migraines because of concerns over the potential
      limitation of compensatory vasodilatory capacitance. There are seven case reports
      in the literature of an association between stroke and the use of beta blockers
      in migraineurs. Prevention using divalproex sodium and verapamil is favored by
      many headache specialists. Triptans are contraindicated in the treatment of
      patients with hemiplegic or basilar migraine because of concern over the
      potential for cerebral vasoconstriction. The frequency of migraine is usually
      unchanged with the use of oral contraceptives although, occasionally, migraine
      may occur for the first time or increase in frequency. Studies have produced
      conflicting results as to whether low-dose estrogen oral contraception increases
      the risk of stroke. Migraine alone increases the risk of stroke, at least in
      women under the age of 45 years. Most women with migraine without aura and
      migraine with visual aura lasting less than 1 hour can safely use low-dose
      estrogen oral contraceptives when there are no other contraindications. Those
      with aura symptoms such as hemiparesis or dysphasia or prolonged focal neurologic
      symptoms and signs lasting more than 1 hour should avoid starting low-dose
      estrogen oral contraceptives and stop the medication if they are already taking
      it.

PMID- 11471759
TI  - Multiple sclerosis treatment 2001.
AB  - Trials of new MS drugs now require MR imaging and clinical data and entail
      enormous expense. Therefore, science can ask and answer only a limited number of
      questions, so physicians must use their clinical acumen to judge (or conjecture)
      the best treatments for their patients. The drugs discussed earlier will dominate
      MS therapy in the next few years, but further advances may come from one of the
      more than forty new agents now under investigation for alleviating MS. It is an
      exciting time for patients and their doctors.

PMID- 11471760
TI  - Parkinson's disease.
AB  - A number of changes have occurred in the management of Parkinson's disease in
      recent years, with the development of new therapeutic strategies based upon
      advances in pharmacotherapy and interventional procedures. The treatment of
      patients with Parkinson's disease is considered here with these advances in mind.
      Potential neuroprotective agents that might slow disease-progression are also
      considered, but at the present time these agents are more of academic interest
      than clinical relevance and their role remains to be established. Ablative
      surgery and stimulation procedures are also helpful in the management of
      Parkinson's disease, and the utility and limitations of these approaches are
      briefly summarized.

PMID- 11471761
TI  - Treatment of tremor and dystonia.
AB  - Treatment of movement disorders has expanded beyond traditional therapies with
      oral medications to include injection of drugs like botulinum toxin and the use
      of surgical interventions in cases that do not respond to medical therapy. This
      article provides an overview to the diagnosis and treatment of tremor and
      dystonia. The distinguishing features of rest, postural, and kinectic tremor are
      detailed with medical and surgical modalities for treatment. A discussion of
      idiopathic and secondary dystonia with focus on diagnosis and medical and
      surgical treatments encompasses the second part of the article.

PMID- 11471762
TI  - Current neuro-ophthalmic therapies.
AB  - The clinical characteristics, differential diagnosis, and treatment options are
      presented for five different categories of neuro-ophthalmic disease. Nystagmus,
      optic neuritis, diplopia, pseudotumor cerebri, and temporal arteritis, are
      frequently encountered in neuro-ophthalmic practice. This article focuses on
      current therapies for these neuro-ophthalmic disorders. Potential differences in
      approach to pediatric versus adult patients are emphasized.

PMID- 11471763
TI  - Sleep disorders.
AB  - Many pharmacologic and nonpharmacologic strategies are available to treat sleep
      disorders successfully. Conventional stimulants and the new stimulant modafinil
      have roles to play in the management of narcolepsy and idiopathic hypersomnia.
      Knowledge of the properties and clinical effects of these drugs allows adequate
      doses of medications to be used with the goal of attaining as maximal alertness
      as possible. A range of dopaminergic agents is available to treat restless legs
      syndrome; other medications such as opiates, benzodiazepines, and anticonvulsants
      can also be used. Successful use of the dopaminergic agents depends on an
      understanding of the phenomena of augmentation, rebound, and tolerance. Arousal
      parasomnias can be treated with behavioral methods such as hypnosis and drug
      therapy. Clonazepam provides relief of the symptoms in most patients with REM
      sleep behavior disorder.

PMID- 11471764
TI  - Treatment  approaches for Guillain-Barre syndrome and chronic inflammatory
      demyelinating polyradiculoneuropathy.
AB  - GBS and CIDP are important treatable forms of acquired peripheral neuropathies.
      GBS is a heterogeneous disorder representing at least five different entities.
      Three are predominantly motor: AIDP, AMSAN, and AMAN. Fisher syndrome and acute
      panautonomic neuropathy are other variants. Treatment for all of these conditions
      is the same and includes either plasma exchange or intravenous immunoglobulin.
      There is no indication that Guillain-Barre patients respond to corticosteroids.
      At the present time, it is uncertain if CIDP represents one or more disorders.
      Evidence favors a syndrome composed of more than one entity accounting for (1)
      clinical variations from subject-to-subject, ranging from symmetrical to focal
      neurologic deficits; (2) course variations from slowly progressive to step-wise,
      to relapsing; and, (3) laboratory variations in nerve conduction studies, spinal
      fluid protein, and nerve biopsy findings. CIDP patients respond to
      corticosteroids in contrast to those with GBS. CIDP improves with intravenous
      immunoglobulin and plasma exchange, paralleling the findings in GBS. Specific
      regimens of treatment for both GBS and CIDP are presented in this article and
      considerations that might influence one treatment regimen over another are
      discussed.

PMID- 11471765
TI  - Therapy in neuromuscular disease.
AB  - The therapy of myasthenia gravis and inflammatory myopathy are discussed in
      detail in this article. The discussion of these two disorders illustrates the
      extraordinary progress that has been achieved in the therapy of neuromuscular
      disease.

PMID- 11471766
TI  - Treatment of degenerative cervical disc disease.
AB  - The different clinical presentations and treatment options available to treat
      neck pain from degenerative disc disease have been discussed. With proper patient
      selection, good correlation between clinical and radiographic findings, and
      selecting the correct procedure for each patient, surgical treatment of cervical
      radiculopathy and myelopathy can be one of the most gratifying operations
      performed in neurosurgery.

PMID- 11471767
TI  - Vertigo.
AB  - Vertigo is a common symptom among outpatients. There are several causes for
      vertigo, and each cause requires a specific treatment. Depending on the cause,
      treatment includes change in drugs, physical therapy, bedside maneuvers, life
      style, and diet. All forms of treatment can be done by neurologists in an
      outpatient setting.

PMID- 11471768
TI  - Epilepsy.
AB  - The successful management of epilepsy requires a thorough and individualized
      approach that accurately establishes the patient's seizure type(s) and, when
      appropriate, epilepsy syndrome. Selection of pharmacologic and nonpharmacologic
      therapy should be rational and tailored to each patient. In this manner,
      clinicians are able to take advantage of new treatments to minimize the impact of
      seizures, treatment side effects, and epilepsy-related psychosocial difficulties
      on their patients, thereby enabling them to function in society at the highest
      possible level.

PMID- 11471769
TI  - Evidence-based treatment of patients with ischemic cerebrovascular disease.
AB  - The results of trials that study patients with defined lesions (atrial
      fibrillation without valvular heart disease, various severities of carotid artery
      stenosis in the neck, intracranial artery stenosis) are very helpful for
      clinicians caring for patients with those conditions. On the other hand, trials
      that group all patients with brain ischemia together are not very helpful. Modern
      technology now makes it possible to define quickly and safely: (1) the location,
      nature, and severity of causative cerebrovascular, cardiac, and aortic lesions;
      (2) blood constituents and coagulability; and, (3) the presence, location, and
      severity of ischemic brain damage. As in all medicine, treatment should be aimed
      at the cause of disease, not the time course and severity of present damage.
      Clearly, more trials are needed in patients who have been studied thoroughly
      using modern technology. Until then, clinicians must understand the context of
      the trial data to determine if the results are applicable to Mr. or Ms. Jones,
      and the patients sitting before them in the office or in the hospital bed.

PMID- 11471770
TI  - The "Dorian Gray Syndrome": psychodynamic need for hair growth restorers and
      other "fountains of youth.".
AB  - The psychic-dynamic factors underlying the hypochondriac disorder involving an
      obsessive preoccupation with physical attractiveness (dysmorphophobia) and the
      treatment possibilities for some manifestations of this syndrome have been
      examined. This psychosomatic illness frequently leads to the taking of
      finasteride, a medication that halts the balding process in cases of androgenetic
      alopecia or even stimulates renewed hair growth. The nosological demarcation of
      the disorder requires the differential diagnosis of depressive, hypochondriac and
      delusionary disorders. The psychodynamics involved, as deduced from 2 case
      studies, takes the form of an expansion of the patients' reductionist
      perspective, characterized by an emphasis on external types extending to a
      psychogenetic attitude with regression into narcissistic fixation. The authors
      seek eternal youth which is a "leitmotif' of the disorder, and they apply the
      term "Dorian Gray Syndrome" after Oscar Wilde's novel. The treatment recommended
      is a course of intensive psychotherapy; often the topic of "life-style
      medication" must be introduced before the specific narcissistic conflicts behind
      the current symptoms can be treated.

PMID- 11471771
TI  - Body dysmorphic disorder and life-style drugs. Overview and case report with
      finasteride.
AB  - The body dysmorphic disorder is the repeated preoccupation with a minimal or non
      evident defect and includes a wide spectrum of imagined defects in appearance.
      These patients present themselves in every clinical practice and are
      extraordinarily difficult to treat. The focus of the preoccupation concerns head,
      face, chest and the genital area. Following the introduction of the new "life
      style" drug, finasteride, we observed a dramatic increase in the number of
      patients suffering from body dysmorphic disorder attending our clinic for skin
      diseases in Erfurt. These patients frequently contact their doctor demanding
      specifically for prescription of a particular life-style drug. However, there is
      no indication for using life-style drugs for the treatment of a body dysmorphic
      disorder. The appropriate treatment includes psychotherapy and
      psychopharmacological treatment.

PMID- 11471772
TI  - The influence of CYP2D6 polymorphism on the antiarrhythmic efficacy of
      propafenone in patients with paroxysmal atrial fibrillation during 3 months
      propafenone prophylactic treatment.
AB  - OBJECTIVE: Propafenone (PPF) is an antiarrhythmic, Class Ic agent. Its metabolism
      is genetically controlled by a cytochrome P450 isoenzyme named CYP2D6, which
      shows polymorphism in human population. The aim of this paper was to determine
      the correlation between the antiarrhythmic efficacy of PPF and the oxidation
      phenotype. SUBJECTS AND MATERIAL: The study group consisted of 42 patients, aged
      36 to 75 years, suffering from paroxysmal atrial fibrillation (AF). The oxidation
      phenotype was described by the metabolic ratio (MR) of sparteine. The MR value
      separated the group of poor metabolizers (MR > 20) from the group of extensive
      metabolizers (MR < 20) with the subgroup of very extensive metabolizers (MR < 1).
      METHOD: The study was conducted during a 3-month PPF therapy for the prophylaxis
      of paroxysmal atrial fibrillation. PPF was given orally, 300-450 mg/day. The
      oxidation phenotype was checked prior to the administration of PPF. Serum
      concentration of PPF at 7, 11 days and the end of PPF therapy were determined.
      Statistical analysis of data was performed with the chi2 test and the Pearson's
      correlation methods. RESULTS: In the group of 42 patients, PPF therapy was 100%
      effective in poor metabolizers (PM). In extensive metabolizers (EM), 61% efficacy
      was observed with efficacy 0% in very extensive metabolizers (VEM). The
      correlation between oxidation phenotype and the ability to maintain sinus rhythm
      (SR) was statistically significant (r = 0.414, p < 0.05). CONCLUSIONS: The
      antiarrhythmic efficacy of propafenone depends on the oxidation phenotype; 100%
      efficacy occurred in the group of poor metabolizers whereas PPF, at the dose
      tested, was ineffective in very extensive metabolizers.

PMID- 11471773
TI  - Midazolam and cortisol metabolism before and after CYP3A induction in humans.
AB  - INTRODUCTION: CYP3A is responsible for the metabolism of numerous endogenous and
      exogenous compounds. Several substrates of CYP3A have been investigated to assess
      the CYP3A-metabolizing capacity of an individual in an attempt to predict the
      rate of metabolism of other CYP3A substrates. Two such tests of CYP3A activity
      are the midazolam plasma clearance after its intravenous administration and the
      6beta-OH cortisol urinary ratio. Possible correlations between these 2 tests were
      investigated before and after treatment with rifampin in a group of healthy
      volunteers. METHODS: Pharmacokinetic parameters of midazolam and 6beta-OH
      cortisol urinary ratio were evaluated in 8 volunteers before and after 6 days
      treatment with rifampin, a potent inducer of CYP3A, and after cessation of
      rifampin treatment. RESULTS: Midazolam systemic clearance and the 6beta-OH
      cortisol urinary ratio were significantly higher at Days 7 and 10 than at Day 0.
      There was a strong positive correlation between these 2 parameters (r = 0.70, p <
      0.001). In contrast, no correlation was observed between the ratio of the AUCs of
      1'-OH midazolam vs. midazolam (AUC0-1(1'-OH)/AUC0-t(MDZ)) or the ratio of plasma
      concentration of 1'-OH midazolam vs. midazolam (C30 min(1'-OH)/C30 min(MDZ)) and
      the 6beta-OH cortisol urinary ratio (r = 0.05, p = 0.82; r = 0.04, p = 0.88,
      respectively). Considering only data obtained before or after treatment with
      rifampin, however, no correlation was observed between midazolam systemic
      clearance and the 6beta-OH cortisol urinary ratio. CONCLUSIONS: These data
      demonstrate that there is a strong positive correlation between systemic
      midazolam clearance and 6beta-OH cortisol urinary ratio before and after
      induction. This suggests that the 6beta-OH cortisol urinary ratio test is a non
      invasive alternative to the use of systemic midazolam clearance for monitoring
      the time-course of CYP3A induction.

PMID- 11471774
TI  - Psycho- and immunopharmacological factors relevant to selection of volunteers in
      clinical studies.
AB  - There are many well-known factors and variables which play a role in the
      evaluation of pharmacokinetic and pharmacodynamic results gained from healthy
      volunteers. The genetic constitution is influenced by age, sex, circadian and
      seasonal variations, dietary factors, immunological function, alcohol intake,
      smoking, etc. Vesell repeatedly pointed out these facts some time ago [Vesell
      1982, Vesell and Passananti 1977]. Since Janke [1964], we have suspected that
      personality traits can also influence the drug response. The following overview
      is dedicated to this field designated as differential psychopharmacology which,
      from the point of view ofthe author, has been given too little attention by
      pharmacologists and clinical pharmacologists. It has been demonstrated that the
      effect of psychotropic drugs, including placebo, can be differentially influenced
      by personality traits, e.g. introversion/extroversion, high level neuroticism/low
      level neuroticism and success motivation/failure motivation. For example,
      relatively high doses of diazepam (0.3 mg/kg), when compared to placebo, only
      impaired the psychophysical performance of extroverted volunteers whereas
      introverted volunteers remained unaffected. Pharmacokinetic parameters, e.g.
      absorption, biotransformation, can also be affected by the level of neuroticism
      or by anxiety, as demonstrated for diazepam, caffeine, paracetamol and
      theophylline. The absorption kinetics of diazepam and caffeine clearly differ
      between volunteers with high neuroticism scores and those with low neuroticism
      scores. Emotionally unstable volunteers absorbed the substances more quickly and
      more completely than emotionally stable volunteers. There were surprising
      differences in various immunological indices between dominant and submissive
      subjects. In dominant volunteers the immune system was more activated than in
      submissive volunteers. In the future, it will become increasingly necessary to
      obtain results for such target groups and to avoid generalized data, which may
      conceal the actual events. Differential clinical psycho-neuro-immunopharmacology
      may be an approach which is helpful in the development of "volunteer models" for
      clinical research in Phase I.

PMID- 11471775
TI  - The effects of captopril on serum digoxin levels in patients with severe
      congestive heart failure.
AB  - The effects of captopril on serum digoxin concentrations were studied in 8
      patients with severe (NYHA Class IV) congestive heart failure. Serum digoxin
      concentrations were determined before and after the administration of captopril
      for 1 week in patients on chronic digoxin therapy. Each patient who was taking
      0.25 mg of digoxin PO q.d., was administered 12.5 mg of captopril PO t.i.d. for 7
      days. The peak serum concentration of digoxin (Cmax) before and after (on Days 0
      and 7) captopril administration was 1.7+/-0.2 ng/ml and 2.7+/-0.2 ng/ml, the time
      to peak (tmax) was 2.4+/-0.5 h and 1.3+/-0.2 h, and the area under the 24-hour
      digoxin concentration-time curve (AUC0-24h) was 30.0+/-1.5 ng x h/ml and 41.7+/
      3.4 ng x h/ml, respectively. While captopril caused a significant increase in
      peak serum concentration and the area under the digoxin concentration-time curve,
      it decreased the time to digoxin peak (p = 0.01, p = 0.04, p = 0.01,
      respectively). No patient developed evidence of digoxin toxicity. Concomitant
      administration of captopril with digoxin increases serum digoxin concentration in
      patients with severe congestive heart failure.

PMID- 11471776
TI  - Acute effects of a single oral dose of carvedilol on cardiac sympathovagal
      balance in man.
AB  - Modulation of autonomic activity is considered to be a prognostic marker in
      patients with cardiovascular disease. The aim of the present study was to
      evaluate the modulation of sympathovagal balance after single-dose administration
      of carvedilol using various autonomic tests as challenges of sympathovagal
      balance. We conducted a randomized double-blind, placebo-controlled study in 18
      male volunteers and applied a crossover design. While heart rate variability
      (HRV) remained unchanged in 24-hour measurements, modulatory effects on
      sympathovagal balance were demonstrated in controlled autonomic maneuvers at
      expected maximal drug levels of carvedilol: time-dependent HRV parameters
      indicative of vagal tone were increased during controlled breathing (15
      cycles/min) in the supine body position by carvedilol. The percentage of
      successive normal RR intervals > 50 ms (pNN50) was increased to 39.8+/-5.1 vs.
      32.7+/-4.7% in the placebo group (p < 0.05), root mean square successive
      differences (rMSSD) to 81.5+/-10.8 vs. 69.3+/-9.1 ms (p < 0.05 vs. placebo). In
      contrast, carvedilol versus placebo significantly reduced time- and frequency
      domain parameters after an active standing-up procedure. This included rMSSD
      (26.5+/-2.8 ms vs. 34.9+/-3.8 ms), pNN50 (6.9+/-2.2% vs. 12.4+/-2.5%). total
      power (4329+/-592 ms2 vs. 6428+/-1158 ms2), low frequency (1472+/-179 ms2 vs.
      2093+/-284 ms2) and high frequency power (251+/-42 ms2 vs. 353+/-92 ms2) of heart
      rate variability. Apparently, the effects of even small doses of carvedilol, too
      low to induce effects detectable in the 24-hour analysis of HRV testing, can be
      detected on controlled maneuvers of autonomic because of their ability to
      modulate autonomic balance. Under conditions of vagal stimulation, a potentially
      beneficial augmentation of HRV parameters indicative for this component is
      induced by carvedilol, while under conditions of sympathetic activation,
      carvedilol effects seem opposite. Interpretation of the latter results, in
      particular, requires further investigation.

PMID- 11471777
TI  - Antiaggregation effect of alum on human platelets.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of alum on human
      platelet aggregation. METHODS: Platelet-rich plasma fractions were prepared from
      fresh blood drawn from a group of healthy male volunteers. Platelet aggregation
      was induced by various inducers. The percent aggregation was recorded in the
      absence and presence of various concentrations of alum. RESULTS: Alum at
      concentrations less than 1.5 mg/ml inhibited platelet aggregation induced by
      collagen, epinephrine. ADP and thrombin in a dose-dependent manner. The IC50s
      were 0.668, 0.324, 0.250 and 0.191 mg/ml of alum, for collagen-, epinephrine-,
      ADP- and thrombin-induced platelet aggregation, respectively. In contrast, alum
      at concentrations up to 1.5 mg/ml did not inhibit ristocetin-induced platelet
      aggregation. CONCLUSION: Alum has an anti-platelet action and should be used
      cautiously in the treatment of intractable intravesical hemorrhage. Alum is a
      cheap anti-platelet drug that needs further investigation.

PMID- 11471778
TI  - On making a travesty of triability.

PMID- 11471779
TI  - Standards for informed consent in recovered memory therapy.
AB  - Malpractice suits against therapists for either instilling or recovering false
      memories of sexual abuse have increased in the last few years and some of the
      awards have been large. Failure to give informed consent, that is, failing to
      inform patients concerning the risk of recovering false memories, is one of the
      main allegations increasingly made against therapists in recovered memory cases.
      In the landmark case on informed consent, Canterbury v. Spence fashioned a
      standard of disclosure that focused on how material the potential warnings were
      to the patient's decision and specifically stated the standard would be set by
      the law, not by the profession. The court ruled that the "risk or cluster of
      risks" must be disclosed to the patient in a manner that meets the patient's
      "informational needs." A review of relevant literature shows that a substantial
      body of information existed by the early 1990s that warned psychotherapists about
      the risk of false reports of sexual and physical abuse. This article concludes
      that the "risk or cluster of risks" that must be disclosed to a patient
      recovering repressed memories in psychotherapy should have included warnings
      about recovering false memories.

PMID- 11471780
TI  - Commentary: How, when, and whether to use informed consent for recovered memory
      therapy.

PMID- 11471781
TI  - Commentary: Informed consent in psychotherapy--a multidisciplinary perspective.

PMID- 11471782
TI  - Principles and narrative in forensic psychiatry: toward a robust view of
      professional role.
AB  - Recent debates in the ethics of forensic psychiatry have centered on the
      applicability of traditional medical ethics to forensic practice. Two prominent
      theories, one taking a principled approach and another taking a narrative
      approach, have attempted to resolve the tension between medical and legal
      settings. In this article we contend that the two theories are related closely
      and work at two different levels: principles at the level of theory and narrative
      at the level of application. We offer an approach to forensic ethics that
      reconciles competing theoretical views by relating professional role and personal
      integrity.

PMID- 11471783
TI  - Commentary: Forensic psychiatry and ethics--the voyage continues.

PMID- 11471784
TI  - Commentary: A broadened conception of forensic psychiatric ethics.

PMID- 11471785
TI  - Attention deficit hyperactivity disorder, reading disability, and personality
      disorders in a prison population.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) has long been recognized in
      children, and for many the disorder persists into adulthood. There is a growing
      concern that the adults with ADHD who have the least favorable outcome, are among
      those who end up in prison. The aim of this study was to assess childhood ADHD
      and its persistence into adulthood among a representative sample of Norwegian
      prison inmates, as well as personality disorders and reading difficulties, which
      in previous studies have been linked to ADHD. The results indicate that
      persistent ADHD is very common among prison inmates. Personality disorders and
      reading difficulties are also common. Psychiatric comorbidity complicates the
      diagnosis of ADHD in adults. A greater awareness about ADHD in adults certainly
      is warranted, especially within the prison system because of the risk of
      misdiagnosing psychiatric disorders and also the risk of missing a condition
      possibly amenable to treatment.

PMID- 11471786
TI  - Psychiatric defenses in New York County: pleas and results.
AB  - Studies that have investigated the use of the insanity defense have revealed that
      the defense is rarely interposed. Few of these studies provide information on the
      use of psychiatric defenses other than insanity or report on how such cases were
      adjudicated (e.g., by trial or plea agreement). The current investigation
      examined all defendants who were indicted for felonies and who proffered any type
      of psychiatric defense in New York County (one of the five counties that comprise
      New York City) from 1988 to 1997. Plea, acquittal, and success rates and the
      manner by which cases were adjudicated are summarized. Prior research reveals
      that the general public believes that the defense is frequently used and often
      succeeds. However, in New York County, psychiatric defenses were proffered by
      only .16 percent of all indicted defendants.

PMID- 11471787
TI  - Expert witness billing practices revisited: a pilot study of further data.
AB  - This pilot study follows up an earlier study of the strategies and rationales by
      which psychiatric expert witnesses bill for their time on a case. Questionnaires
      were answered by participants at a workshop at the Annual Meeting of the American
      Academy of Psychiatry and Law (AAPL). In this follow-up, additional novel billing
      issues were addressed, some subtler than in the original study. In addition,
      responses to one question supported the previous finding that experts billed more
      reasonably when a case was simple. Additional issues included use of fee
      agreements and returning an unpaid-for case. The implications of these findings
      are discussed.

PMID- 11471788
TI  - Post-Daubert admissibility of scientific evidence on malingering of cognitive
      deficits.
AB  - In Daubert v. Merrell Dow Pharmaceuticals, Inc. (1993) the Supreme Court held
      that evidence must be "reliable" to be admissible and for scientific evidence
      "evidentiary reliability" is based on scientific validity. This article addresses
      the question "Do the Rey 15-Item Test ('FIT'), the Test of Memory Malingering
      ('TOMM'), and the Validity Indicator Profile ('VIP') likely meet the Daubert
      standard for admissibility of scientific evidence?" Sensitivity, specificity,
      positive and negative predictive values (PPV and NPV, respectively), and base
      rates of 30 and 15 percent were calculated for each test. Given the existing
      literature on malingering and the implications of a misclassification of
      malingering, we discuss the findings for each of the three tests using a PPV > or
      = 80 percent with a base rate of malingering of < or = 30. Our analyses indicate
      that the Rey 15-FIT fails to meet this standard of scientific validity. In
      contrast, the TOMM shows high specificity and PPV, and our findings suggest
      cautious optimism regarding the VIP. These results are discussed within the
      context of the courts' guidelines for the Daubert standard.

PMID- 11471789
TI  - The business aspects of forensic psychiatry.

PMID- 11471790
TI  - Physician-assisted suicide: reflections of a Maine family physician during the
      Jewish high holidays.

PMID- 11471791
TI  - Sexual predator laws in Canada.

PMID- 11471792
TI  - A duty to the parents of an allegedly abused child? Althaus v. Cohen.

PMID- 11471793
TI  - A review of Stephen Soderbergh's movie, Traffic.

PMID- 11471794
TI  - Role that forensic psychiatrists can play in the litigation process.

PMID- 11471795
TI  - Protein adsorption equilibria and kinetics to a poly(vinyl alcohol)-based
      magnetic affinity support.
AB  - A poly(vinyl alcohol)-based magnetic gel entrapping Fe3O4 colloids has been
      prepared by an emulsification-crosslinking method. The gel was modified with
      Cibacron blue 3GA, and thus a magnetic affinity support was produced. The
      adsorption equilibrium studies showed that the adsorption isotherm of lysozyme
      was nearly rectangular, with a capacity of 254 mg/ml, while the adsorption
      isotherm of bovine serum albumin obeyed the Henry's law. Uptake kinetics of the
      two proteins was investigated and analyzed with a pore diffusion model and a
      homogeneous diffusion model. Experimental results showed that the magnetic
      affinity gel had magnetic responsiveness and favorable properties in protein
      adsorption, and was mechanically and chemically stable.

PMID- 11471796
TI  - Initial evaluation of quantitative performance of chromatographic methods using
      replicates at multiple concentrations.
AB  - The introduction of a novel analytical method must be supported by consistent
      information about its quantitative potentialities; this is critical for whoever
      considers its utilization for an specific application. Unfortunately, literature
      abounds in papers proposing excellent chromatographic methods of analysis that
      have been subjected to comparatively poor quantitative evaluation. The
      methodology proposed in the present work makes use of some of the performance
      characteristics whose measurement is recommended in validation protocols;
      pertinent to this stage of method development are the detection and quantitation
      limits, the linear range and the repeatability. All this information can be
      calculated from the results of a calibration with several replicates at each
      analyte level. Replicates enable the calculation of reproducibility at several
      analyte levels and the estimation of the linear range; more important, replicates
      are necessary to detect changes in peak area standard deviation with analyte
      amount. Regression of calibration data by means of unweighted least-squares
      (ULSR) can only be performed in those cases in which homoscedasticity has been
      previously verified; heteroscedastic calibration data demand regression by means
      of weighted least-squares (WLSR), since ULSR results in gross overestimation of
      prediction limits at low analyte concentration. The proposal is used for the
      preliminary quantitative evaluation of a method for the determination of nine
      biogenic amines by means of pre-column derivatization with dabsyl chloride and
      separation of derivatives by RPLC. Limits of detection are calculated by a
      regression approach and by the classical signal-to-noise ratio method (S/N
      approach). No significant difference was detected for the amines limits of
      detection estimated by WLSR and by the S/N approach; ULSR estimated limits of
      detection are between 7 and 78 times larger than those obtained by the other two
      methods, as a consequence of the heteroscedasticity of calibration data.

PMID- 11471797
TI  - Modeling and analysis of the dynamic behavior of mechanisms that result in the
      development of inner radial humps in the concentration of a single adsorbate in
      the adsorbed phase of porous adsorbent particles observed in confocal scanning
      laser microscopy experiments: diffusional mass transfer and adsorption in the
      presence of an electrical double layer.
AB  - A theoretical model for adsorption of a single charged adsorbate that accounts
      for the presence of an electrical double layer in the pores of adsorbent
      particles is constructed and solved. The dynamic behavior of the mechanisms of
      the model can result in the development of inner radial humps (concentration
      rings) in the concentration of a single charged analyte (adsorbate) in the
      adsorbed phase of porous adsorbent particles. The results of the present work
      demonstrate the implication of the concept regarding the effect of the presence
      of an electrical double layer in the pores of adsorbent particles and the induced
      interactions between the electrostatic potential distribution and the mechanisms
      of mass transport of the species by diffusion, electrophoretic migration, and
      adsorption. Furthermore, the mechanisms of the model could explain qualitatively
      the development of the concentration ring (hump) observed in confocal scanning
      laser microscopy experiments.

PMID- 11471798
TI  - Immobilized penicillin G acylase as reactor and chiral selector in liquid
      chromatography.
AB  - In this paper, the use of penicillin G acylase (PGA) as a biocatalyst and as a
      chiral selector is described. Penicillin G-acylase is an interesting enzyme used
      in the manufacture of semisynthetic antibiotics and, in particular, in the
      production of 6-APA by hydrolysis of penicillin G. Five PGA-based HPLC columns
      have been prepared by using two different silica supports by employing two
      immobilization methods, namely "in situ" and "in batch". The effects of the
      immobilization techniques and of different silica pore size on the catalytic
      properties of the enzyme as well as the applicability of the PGA-bonded
      stationary phases as chiral selectors for a number of chiral drugs have been
      investigated. The HPLC columns based on immobilized PGA combine the hydrolytic
      activity and the chiral recognition properties of PGA, therefore they have been
      used for the development of a combined reaction-separation system for chiral and
      achiral substrates.

PMID- 11471799
TI  - Determination of enantiomer separation factors by nuclear magnetic resonance
      spectroscopy and by chiral liquid chromatography.
AB  - The equilibrium constants K+ and K- for formation of the diastereomeric complexes
      of the two enantiomers of O,O'-dibenzoyltartaric acid (DBTA) with the chiral
      selector N,N'-diallyltartardiamide bis-(4-tert.-butylbenzoate) (TBB) have been
      determined by 1H-NMR. The experiments were performed at different temperatures in
      CDCl3 or in cyclohexane-d12/2-propanol-d8 mixtures. The equilibrium constants
      from the 1H-NMR results have been compared with the retention factors (k')
      obtained from the chromatographic resolution of rac. DBTA on a Kromasil CHI-TBB
      column with the same solvents as mobile phases. A satisfactory correlation
      between the 1H-NMR data and the chromatographic data was found.

PMID- 11471800
TI  - Stability of phenolic compounds during extraction with superheated solvents.
AB  - The stability of nine phenolic compounds in the extraction with superheated
      methanol at different temperatures (40, 50, 100 and 150 degrees C) has been
      tested. The evolution of the same compounds in boiling methanol (65 degrees C) in
      contact with air was also determined. All the assayed phenolic compounds were
      stable under the extraction conditions with the exception of catechin and
      epicatechin (recoveries: 87.4% for catechin and 86.0% for epicatechin at 150
      degrees C and 94.1% for epicatechin at 100 degrees C). Phenolic compounds kept at
      the boiling point of methanol (65 degrees C) showed lower recoveries: gentisic
      acid (85.5%), syringic aldehyde (92.8%), catechin (63.7%) and epicatechin
      (63.4%). Extraction with superheated solvents was also applied to the extraction
      of phenolic compounds from solid wastes of the winemaking process.

PMID- 11471801
TI  - Analysis of intact bacteriohopanepolyols from methanotrophic bacteria by reversed
      phase high-performance liquid chromatography-atmospheric pressure chemical
      ionisation mass spectrometry.
AB  - Direct detection of most intact biohopanoids is not possible using conventional
      GC-MS techniques due to their highly functionalised and amphiphilic nature. Here
      we report the application of a new reversed-phase high-performance liquid
      chromatography method for the direct analysis of acetylated, intact
      bacteriohopanepolyols in solvent extracts of methanotrophic bacteria. Atmospheric
      pressure chemical ionisation mass spectrometric detection provides structural
      information relating to the number and types of functional groups present in the
      four biohopanoids detected: bacteriohopanetetrol, aminobacteriohopanetriol, 
      tetrol and -pentol. The method should facilitate the assessment of hopanoid
      composition of both bacteria and environmental samples.

PMID- 11471802
TI  - Abnormal elution behavior of ornitine derivatized with 1-fluoro-2,4-dinitrophenyl
      5-leucinamide in advanced Marfey's method.
AB  - During the course of establishing the advanced Marfey's method that has been
      developed to non-empirically determine the absolute configuration of constituent
      amino acids in a peptide using LC-MS, we encountered the "ornitine mystery" in
      the di-DLA (2,4-dinitrophenyl-5-leucinamide) derivative such that the elution
      order of ornitine (Orn) was opposite (D-->L) in spite of their relatively long
      retention time. In order to resolve this problem, the elution behavior of several
      mixed DLA and DPEA (2,4-dinitrophenyl-5-phenylethylamine) derivatives with
      different absolute configurations was carefully observed during HPLC. The length
      of the methylene chain in basic amino acids was obviously critical for this
      behavior, because Dab (2,4-diamino-n-butyric acid) and lysine (Lys) did not
      exhibit this abnormality. The presence of the carboxyamide moiety at the omega
      position was also essential for this phenomenon, because it was never observed in
      the DPEA derivatives at the omega position. Furthermore, it was found that the
      following combination of absolute configurations of Orn and DLA at the omega
      position only induced this abnormality: D-Orn and L-DLA, and L-Orn and D-DLA.
      This suggested that the structural interaction such as hydrogen bonding between
      the carboxyamide of DLA at the omega position and carboxylic acid at the alpha
      position in these derivatives reduced their retention power on the reversed-phase
      column.

PMID- 11471803
TI  - Functional polymer affinity matrix for purifying hexahistidine-tagged recombinant
      protein.
AB  - A functional polyacrylic acid (PAA) adsorbent has been prepared for metal chelate
      affinity chromatography. It has been found to chelate nickel ion Ni2+ strongly,
      and was evaluated for the ability to bind proteins containing neighbouring
      histidine residues. The principle of the technique was illustrated with Aeromonas
      hydrophila outer membrane protein OmpTS. DNA elements coding for adjacent
      histidines were fused to the Aeromonas hydrophila ompTS gene. Subsequent
      expression in E. coli resulted in the production of hybrid protein His6-OmpTS
      that could be purified by Ni2+-PAA affinity chromatography. The remarkable
      specificity found makes it an attractive addition to the range of adsorbents for
      metal chelate affinity chromatography.

PMID- 11471804
TI  - Determination of the UV filters worldwide authorised in sunscreens by high
      performance liquid chromatography. Use of cyclodextrins as mobile phase modifier.
AB  - Simultaneous determination of organic UV filters worldwide authorised in
      sunscreen formulations was performed by HPLC with UV spectrophotometric
      detection. The filters determined were: benzophenone-4, benzophenone-3, butyl
      methoxydibenzoylmethane, octyl dimethyl PABA, octyl methoxycinnamate, homosalate
      and octyl salicylate. A C18 stationary phase and an isocratic mobile phase of
      ethanol-water-acetic acid (70:29.5:0.5) containing 65.4 mM of hydroxypropyl-beta
      cyclodextrin, were used with a flow-rate of 0.6 ml/min. UV measurements were
      carried out at 313 nm. The time required for the analysis was 20 min and the
      limits of detection were between 1.5 and 2.3 mg/l. The procedure proposed
      provides a green analytical method with a basic instrumental configuration, it is
      fast and accurate and does not involve highly toxic organic solvents.

PMID- 11471805
TI  - Ion chromatography on chelating stationary phases: separation of alkali metals.
AB  - Analytical 250x4.6 mm I.D. columns packed with iminodiacetic acid (IDA)
      derivatised silica were used to separate alkali metal ions and the ammonium ion
      in combination with non-suppressed conductivity detection. The addition of 2.5-10
      mmol/l of the macrocyclic crown ether 18-crown-6 to the nitric acid eluent
      resulted in a change in the elution order and a significant improvement in the
      resolution between potassium and ammonium because of selective complexation of
      potassium. However, the admixture of 15-crown-5 did not improve the resolution of
      lithium and sodium, although 15-crown-5 is a selective complexing agent for
      sodium. Retention and resolution of lithium, sodium, ammonium, cesium, rubidium
      and potassium ions increased at lower temperatures down to 1 degree C. The
      simultaneous separation of alkali and transition metals under isocratic
      conditions was achieved with an eluent comprising 10 mmol/l 18-crown-6, 1.5
      mmol/l dipicolinic acid, and 1.9 mmol/l nitric acid. The chromatographic system
      enabled the quantitation of alkali metal ions with detection limits in the low
      ppb range and excellent linearity. Finally, the applicability of the method was
      approved by quantitation of sodium, ammonium and potassium in different water
      samples.

PMID- 11471806
TI  - Mass spectrometry and mass-selective detection in chromatography.
AB  - An overview of chromatography-mass spectrometry coupling is presented here,
      focussing mainly on possibilities offered by this detection technique. GC-MS and
      HPLC-MS are the two most often used variants, which have quite different
      characteristics. Various mass-spectrometric possibilities are briefly discussed:
      ionization techniques, determination of elemental formulas, structural
      information and the question of sensitivity and selectivity. Options for mass
      spectrometric instrumentation and applications of tandem mass spectrometry are
      also mentioned.

PMID- 11471807
TI  - Comparison of analytical techniques to quantify malondialdehyde in milk powders.
AB  - Several analytical methods were compared to quantify malondialdehyde (MDA) in
      milk powders. Modified thiobarbituric acid (TBA) methods, using either visible
      spectrophotometry (direct absorbance reading or after third derivative
      transformation of the spectrum) or HPLC, required derivatisation at elevated
      temperature, which appeared to catalyse artefactual MDA formation and thus
      overestimate the MDA content. In contrast to the TBA derivatisation method, the
      measurement of MDA as the dinitrophenylhydrazone derivative by HPLC or as the
      phenylhydrazone product by GC-MS with a deuterated internal standard resulted in
      lower estimates in the ranges of 2-17- and 3-30-fold, respectively; apparently
      due to the milder derivatisation conditions. The estimates of MDA determined by
      both HPLC-UV and GC-MS techniques result in lower values which are similar in
      magnitude even though the GC-MS technique is more sensitive.

PMID- 11471808
TI  - Laser-enhanced ionization and laser-induced atomic fluorescence as element
      specific detection methods for gas chromatography. Application to organotin
      analysis.
AB  - We have demonstrated that flame laser-enhanced ionization (LEI) and flame laser
      induced atomic fluorescence (LIAF) techniques can be used as, alternative
      sensitive detectors for gas chromatographic (GC) analysis of organotin compounds.
      These two element-specific detection methods are free from interferences from the
      organic solvent. Two types of LEI schemes for Sn detection are employed. For the
      two-step LEI scheme (TLEI), the tin atoms in the flame were stepwise excited and
      then ionized collisionally. In contrast, in detection with the single-step LEI
      scheme (SLEI), only one dye laser is used. For the analysis of tetramethyltin and
      tetraethyltin, the GC-TLEI, GC-SLEI, and GC-LIAF systems yield linear dynamic
      ranges of 0.015-400, 0.39-600 and 0.5-600 ng, respectively. The corresponding
      detection limits reach 0.15, 3.9 and 5.0 mg/l, with absolute quantities
      corresponding to 15, 390 and 500 pg, respectively, for an injection volume of 0.1
      microl. These detection methods prove to be more sensitive and selective than the
      conventional flame ionization detection, which achieves absolute detection limits
      of 800 and 1667 pg for tetraethyltin and tetramethyltin, respectively, under
      identical GC conditions.

PMID- 11471809
TI  - Solid-phase extraction of polycyclic aromatic hydrocarbons in surface water.
      Negative effect of humic acid.
AB  - The effect of humic acid on solid-phase extraction of polycyclic aromatic
      hydrocarbons (PAHs) from surface water was studied. The hydrophobic PAHs show
      significant association with humic acid, and this was confirmed to be the cause
      of negative effect when conventional reversed-phase solid-phase extraction (RP
      SPE) was employed to extract the analytes from aqueous samples. As an
      alternative, dynamic ion-exchange (DIE) SPE could simultaneously extract both the
      fraction of the analytes which was associated with humic acid, and that which was
      freely dissolved. Using the 16 US Environmental Protection Agency priority PAHs
      as model compounds, the recoveries of the highly hydrophobic components by DIE
      SPE were 10-30% higher than those by RP-SPE for a 1000-ml water sample dissolved
      with Aldrich humic acid (of 4.1 mg/l dissolved organic carbon content). A similar
      result was also obtained for 500 ml of natural surface water although the
      difference in recoveries between the two methods for this sample was smaller than
      that for the simulated sample. For validation of the method, the artifacts in
      connection with DIE-SPE in extracting the fraction of analytes which was freely
      dissolved and that which was associated with humic acid were investigated.

PMID- 11471810
TI  - On-line, inlet-based trimethylsilyl derivatization for gas chromatography of mono
      and dicarboxylic acids.
AB  - An on-line, inlet-based trimethylsilyl (TMS) derivatization technique was
      optimized and evaluated for quantitative analysis of mono- and dicarboxylic
      acids. The technique involves co-injection of sample and reagent followed by gas
      phase formation of TMS derivatives and analysis by gas chromatography with flame
      ionization detection. Derivatization efficiencies were determined by comparing
      measured and theoretical effective carbon numbers and used to optimize the
      technique with respect to experimental parameters. For analysis of C5-C17
      monocarboxylic acids and C2-C10 dicarboxylic acids under optimized conditions,
      average derivatization efficiencies were > or = 94%, average measurement
      uncertainties were < or = 5%, and detection limits were approximately 2 ng. The
      technique was applied to the analysis of carboxylic acids generated from the
      ozonolysis of cyclic alkenes in a smog chamber.

PMID- 11471811
TI  - Gas chromatographic characterization of vegetable oil deodorization distillate.
AB  - Because of its complex nature, the analysis of deodorizer distillate is a
      challenging problem. Deodorizer distillate obtained from the deodorization
      process of vegetable oils consists of many components including free fatty acids,
      tocopherols, sterols, squalene and neutral oil. A gas chromatographic method for
      the analysis of deodorizer distillate without saponification of the sample is
      described. After a concise sample preparation including derivatization and
      silylation, distillate samples were injected on column at 60 degrees C followed
      by a gradual increase of the oven temperature towards 340 degrees C. The
      temperature profile of the oven was optimized in order to obtain a baseline
      separation of the different distillate components including free fatty acids,
      tocopherols, sterols, squalene and neutral oil. Good recoveries for delta
      tocopherol, alpha-tocopherol, stigmasterol and cholesteryl palmitate of 97, 94.4,
      95.6 and 92%, respectively were obtained. Repeatability of the described gas
      chromatographic method was evaluated by analyzing five replicates of a soybean
      distillate. Tocopherols and sterols had low relative standard deviations ranging
      between 1.67 and 2.25%. Squalene, mono- and diacylglycerides had higher relative
      standard deviations ranging between 3.33 and 4.12%. Several industrial deodorizer
      distillates obtained from chemical and physical refining of corn, canola,
      sunflower and soybean have been analyzed for their composition.

PMID- 11471812
TI  - Stability studies of carbamate pesticides and analysis by gas chromatography with
      flame ionization and nitrogen-phosphorus detection.
AB  - As a result of thermal stability studies of carbamate pesticides, a method has
      been proposed for their direct determination by gas chromatography in the ranges
      1-20 and 0.1-1 mg l(-1), using flame ionization and nitrogen-phosphorus
      detection, respectively. The method allows the determination of propham,
      propoxur, carbofuran, carbaryl, methiocarb, isopropoxyphenol and naphthol in
      powdered potato samples. The analytes were previously extracted with a light
      petroleum-dichloromethane (1:1, v/v) mixture and preconcentred by solid-phase
      extraction through a C8 cartridge. The recoveries obtained from spiked potato
      samples (n=4 replicates) at two concentration levels, 10 and 0.5 mg of pesticide
      per kg of sample, were in the ranges 72-115 and 50-73%, with relative standard
      deviations of 2-7 and 5-8%, respectively. The detection limits were 50-210 and 41
      53 microg kg(-1) with flame ionization and nitrogen-phosphorus detection,
      respectively, and reaching the maximum residue levels, 0.05 mg kg(-1) for
      methiocarb and propoxur, set by the Real Decreto 280/1994 (based on the European
      directive).

PMID- 11471813
TI  - Determination of residues of endosulfan and five pyrethroid insecticides in
      virgin olive oil using gas chromatography with electron-capture detection.
AB  - A simple, fast and economical method has been developed for the determination of
      endosulfan and five pyrethroid insecticides, cypermethrin, deltamethrin,
      fenvalerate, lambda-cyhalothrin and permethrin, in virgin olive oil. The method
      uses a Sep-Pak alumina-N column cleanup after a liquid-liquid extraction or low
      temperature precipitation step, and gas chromatography (GC) with electron-capture
      detection. The matrix effect was assessed for the GC systems used. Recoveries
      were 71-91% with RSD values of 6-17%. The method was applied to 338 virgin olive
      oil samples for monitoring of residues of these pesticides. Cypermethrin and
      lambda-cyhalothrin were detected at the limit of quantification in one sample
      each, while 22% of samples contained endosulfan residues, mostly at very low
      levels ranging from 0.02 to 0.57 mg/kg.

PMID- 11471814
TI  - Applications of the Chiralpak AD and Chiralcel OD chiral columns in the
      enantiomeric separation of several dioxolane compounds by supercritical fluid
      chromatography.
AB  - Two chiral columns based on polysaccharide derivatives (Chiralpak AD and
      Chiralcel OD) have been tested for the chiral separation of several dioxolane
      compounds, using supercritical fluid chromatography. The compounds studied
      included ketoconazole and some of its precursors. The effect of the different
      modifiers and the pressure, on the chromatographic parameters was also evaluated.
      In general, the alcohol modifiers provided better results than acetonitrile, and
      all the compounds could be separated with these two columns, but the selection of
      the column depends on the kind of compound.

PMID- 11471815
TI  - Resolution of structural isomers of sialylated oligosaccharides by capillary
      electrophoresis.
AB  - The resolution of structural isomers in mixtures of oligosaccharides is often
      challenging. Capillary electrophoresis was employed to separate three sets of
      structural isomers of sialylated oligosaccharides found in human milk and bovine
      colostrum. Different running buffers were necessary to achieve optimal baseline
      resolution. To resolve 3'- and 6'-sialyllactoses, 0.2 M aqueous sodium phosphate
      containing 40% methanol as an organic modifier was used as a running buffer. To
      resolve 3'- and 6'-sialyllactosamines, 0.4 M aqueous sodium phosphate without
      organic modifier was used. Baseline resolution of sialyllacto-N-tetraose-a and -b
      and sialyllacto-N-neotetraose-c was achieved with a 0.4 M Tris-HCl buffer
      containing 250 mM sodium dodecyl sulfate and 10% methanol as the organic
      modifier. Thus, each of these sets of structural isomers of sialylated
      oligosaccharides required a unique running buffer with respect to buffer type,
      concentration, pH, presence of organic modifiers, and surfactants. Similar
      electrophoresis conditions may be useful for resolving and analyzing other
      structural isomers of acidic oligosaccharides by capillary electrophoresis.

PMID- 11471816
TI  - Micellar electrokinetic chromatography of polyamines and monoacetylpolyamines.
AB  - A selective procedure for qualitative and quantitative analysis of ten polyamines
      by micellar electrokinetic chromatography (MEKC) was developed. Benzoylated
      polyamines and acetylpolyamines in micellar phase of SDS (10 mM) were separated
      at 25 degrees C by 20 mM borate buffer pH 8.5, containing 8% ethanol, with an
      applied voltage of 25 kV (5 microA) and then detected at 198 nm. The experimental
      factors and operational parameters were optimized by performing analysis at
      different surfactant concentrations, pH, voltage and temperature with and without
      ethanol. The repeatibility of migration times and peak heights is a peculiarity
      of the method here described.

PMID- 11471817
TI  - Separation of radioactive metabolites in cultured tea cells fed with
      [14C]phenylalanine using high-speed counter-current chromatography.
AB  - Separation of radioactive metabolites in cultured tea cells fed with
      [14C]phenylalanine was conducted using high-speed counter-current chromatography.
      Among seven components obtained our studies focused two metabolites, i.e. (-)
      epicatechin and D,L-catechin. The specific radioactivity of (-)-epicatechin was
      212.01 KBq/mg, amounting to 8.5% of the total radioactivity of ethyl acetate
      extract while that of D,L-catechin was 1.0006 MBq/mg or 5.4% of the total.

PMID- 11471818
TI  - Liquid chromatographic determination of less polar ginsenosides in processed
      ginseng.
AB  - Reversed-phase LC with an evaporative light scattering detector (ELSD) is used
      for the determination of less polar ginsenosides in processed ginseng. These
      ginsenosides include ginsenosides F4, Rg3, Rg5, Rg6, Rk1, Rk3, Rs3, Rs4, and Rs5.
      The method used a C18-bonded silica column with a CH3CN/H2O/CH3COOH gradient
      elution. (20R) and (20S) epimers and geometric isomers at the C-20 position of
      ginsenosides, which are not generally separated by amino columns, were now
      clearly separated.

PMID- 11471819
TI  - On the pheromone of the asparagus fly, Platyparea poeciloptera.

PMID- 11471820
TI  - Menadione-catalyzed O2- production by Escherichia coli cells: application of
      rapid chemiluminescent assay to antimicrobial susceptibility testing.
AB  - This study proposes a novel chemiluminescent assay of bacterial activity. Luminol
      chemiluminescence (LC) was amplified on addition of menadione to Escherichia coli
      suspension, and it was effectively inhibited by addition of superoxide dismutase
      rather than catalase. This fact suggests that H2O2 produced from O2 by superoxide
      dismutase is decomposed by catalase of E. coli. NAD(P)H:menadione reductase
      activities in periplasm and cytosol corresponded to the amplification of
      menadione-catalyzed LC, and outer and cytoplasmic membranes were only slightly
      involved in the LC. The total activity and Vmax of NAD(P)H:menadione reductase in
      the cytoplasm were greater than those in the periplasm. A transient increase in
      menadione-catalyzed LC was observed in the exponential phase and the LC decreased
      in the stationary phase during growth of E. coli. Menadione-catalyzed LC was
      sensitive to antibiotic action. A decrease in menadione-catalyzed LC by the
      impairment of membrane functions and by the inhibition of protein synthesis was
      observed at 5 min and 3 hr, respectively. These findings suggest the possibility
      that menadione-catalyzed luminol chemiluminescent assay is applicable to rapid
      antimicrobial assay because LC is sensitive to the change in growth and cytotoxic
      events caused by antimicrobial agents.

PMID- 11471821
TI  - Nucleotide sequence and molecular characterization of a dextranase gene from
      Streptococcus downei.
AB  - DNA fragments encoding the Streptococcus downei dextranase were amplified by PCR
      and inverse PCR based on a comparison of the dextranase gene (dex) sequences from
      S. sobrinus, S. mutans, and S. salivarius, and the complete nucleotide sequence
      of the S. downei dex was determined. An open reading frame (ORF) of dex was 3,891
      bp long. It encoded a dextranase protein (Dex) consisting of 1,297 amino acids
      with a molecular mass of 139,743 Da and an isoelectric point of 4.49. The deduced
      amino acid sequence of S. downei Dex had homology to those of S. sobrinus, S.
      mutans and S. salivanus Dex in the conserved region (made of about 540 amino acid
      residues). DNA hybridization analysis showed that a dex DNA probe of S. downei
      hybridized to the chromosomal DNA of S. sobrinus as well as that of S. downei,
      but did not to other species of mutans streptococci. The C terminus of the S.
      downei Dex had a membrane-anchor region which has been reported as a common
      structure of C termini of both the S. mutans and S. sobrinus Dex. The recombinant
      plasmid which harbored the dex ORF of S. downei produced a recombinant Dex enzyme
      in Escherichia coli cells. The analysis of the recombinant enzyme on SDS-PAGE
      containing blue dextran showed multiple active forms as well as dextranases of S.
      mutans, S. sobrinus and S. salivarius.

PMID- 11471822
TI  - Region of heat-stable enterotoxin II of Escherichia coli involved in
      translocation across the outer membrane.
AB  - Heat-stable enterotoxin II of Escherichia coli (STII) is synthesized as a
      precursor form consisting of pre- and mature regions. The pre-region is cleaved
      off from the mature region during translocation across the inner membrane, and
      the mature region emerges in the periplasm. The mature region, composed of 48
      amino acid residues, is processed in the periplasm by DsbA to form an
      intramolecular disulfide bond between Cys-10 and Cys-48 and between Cys-21 and
      Cys-36. STII formed with these disulfide bonds is efficiently secreted out of the
      cell through the secretory system, including TolC. However, it remains unknown
      which regions of STII are involved in interaction with TolC. In this study, we
      mutated the STII gene and examined the secretion of these STIIs into the culture
      supernatant. A deletion of the part covering from amino acid residue 37 to the
      carboxy terminal end did not markedly reduce the efficiency of secretion of STII
      into the culture supernatant. On the other hand, the efficiency of secretion of
      the peptide covering from the amino terminal end to position 18 to the culture
      supernatant was significantly low. These observations indicated that the central
      region of STII from amino acid residue 19 to that at position 36 is involved in
      the secretion of STII into the milieu. The experiment using a dsbA-deficient
      strain of E. coli showed that the disulfide bond between Cys-21 and Cys-36 by
      DsbA is necessary for STII to adapt to the structure that can cross the outer
      membrane.

PMID- 11471823
TI  - Fungal flora on board the Mir-Space Station, identification by morphological
      features and ribosomal DNA sequences.
AB  - This report is on the morphological and molecular biological identification,
      using 18S- and ITS1-rDNA sequences, of the "space fungi" isolated on board the
      Russian Mir-Space Station as the major constituents of the fungal flora. The six
      fungal strains were isolated from air by using an air sampler or from
      condensation. Strains were identified as Penicillium chrysogenum, Aspergillus
      versicolor, or Penicillium sp. by both methods. The species of space fungi were
      common saprophytic fungi in our living environment, potential pathogens, and
      allergens. This study concluded that the environment on board the space station
      Mir allows the growth of potentially pathogenic fungi as true in residential
      areas on the earth. Therefore, to prevent infection or other health disorders
      caused by these fungi, easy and reliable methods should be established to survey
      the fungal flora in a space station.

PMID- 11471824
TI  - Stabilization of cauliflower mosaic virus P3 tetramer by covalent linkage.
AB  - Cauliflower mosaic virus (CaMV) open reading frame (ORF) III encodes a 15 kDa
      protein (P3) that is indispensable for viral infectivity. Although P3 has been
      shown to be a prerequisite for CaMV aphid transmission, its role in viral
      replication remains unknown. We previously showed that P3 forms a tetramer in
      planta and that P3 tetramer co-sediments with viral coat protein on sucrose
      gradient centrifugation, suggesting that a tetramer may be the functional form of
      P3. We presumed that disulfide bonds were involved in tetramer formation because
      1) the tetramer was detected by Western blotting after electrophoresis under non
      reducing conditions, and 2) the cysteine-X-cysteine motif is well conserved in
      CaMV P3 and P3 homologues among Caulimoviruses. Therefore we mutated either or
      both of the cysteine residues of CaMV P3. The mutant viruses were infectious and
      accumulated to a similar extent as the wild-type. An analysis of mutant proteins
      confirmed that the wild-type P3 molecules in the tetramer are covalently bound
      with one another through disulfide bonds. It was also suggested that mutant
      proteins are less stable than wild-type protein in planta. Furthermore,
      sedimentation study suggested that the disulfide bonds are involved in stable
      association of P3 with CaMV virions or virion-like particles, or both. The mutant
      viruses could be transmitted by aphids. These results suggested that the covalent
      bonds in P3 tetramer are dispensable for biological activity of P3 under
      experimental situations and may have some biological significance in natural
      infection in the field.

PMID- 11471825
TI  - Mechanism for maintenance of dominant T helper 1 immune responses in Lewis rats.
AB  - Lewis rats are prone to T helper (Th) 1 immune responses, whereas Brown Norway
      (BN) rats are susceptible to Th2 immune responses. Yet, the precise mechanism of
      induction of the different outcome between these two strains remained elusive. We
      investigated the expression levels of some cytokines, their receptors and
      accessory molecules responsible for the polarization of antigen-specific immune
      response into a predominant Th1 or Th2 profile in Lewis and BN rats. Lymph node
      (LN) cells collected from rats immunized with short ragweed (RW) were used
      directly or after stimulation in vitro with RW for 3 days. Expression of
      cytokines, their receptors and accessory molecules in these LN cells were tested
      by reverse transcriptase-PCR. Culture supernatant was used for ELISA to detect IL
      12 protein. We observed clear differences between these strains in the expression
      of IL-12p40, which was high in LN cells of Lewis rats even before stimulation in
      vitro. In addition, a higher amount of IL-12 was present in the culture
      supernatant in Lewis rats. Upregulation of the expression of IL-12 receptor
      beta1, beta2, IFN-gamma receptor alpha and beta genes were more prominent in
      Lewis rats rather than BN rats. Furthermore, attenuated expression of CD40 and
      CD40 ligand by stimulation in vitro was noted only in BN rats. Changes in
      expression of these molecules by stimulation as well as higher basal level of IL
      12p40 might have led to the activation of Th1 cells in Lewis rats.

PMID- 11471826
TI  - Resistance to antibiotics in injured coliforms isolated from drinking water.
AB  - We studied the antibiotic sensitivity of injured coliforms isolated from drinking
      water of La Plata, Argentina. The antibiotic sensitivity test by the agar
      diffusion method were proved in: Klebsiella oxytoca (14 strains), Enterobacter
      aerogenes (4 strains) and Enterobacter cloacae genomic group 3 (14 strains). We
      found that while these impaired total coliforms were sensitive to piperacillin
      tazobactam (TAZ), netilmicin (NTL), ofloxacin (OFLX), and norfloxacin (NFLX)
      (100%), they had resistant to aminopenicillin-sulbactam (AMS) and nitrofurantoin
      (NIT) (100%). The resistance to antibiotics demonstrated in these strains would
      point to the need to promote a rational and judicious use of antimicrobial agents
      while at the same time implementing a program of active vigilance aimed at
      ensuring the highest quality of drinking water throughout the system.

PMID- 11471827
TI  - Negative incidence of Lyme disease-related Borrelia spp. in Alishan, Taiwan.
AB  - To investigate the prevalence of Lyme disease-related Borrelia species, wild
      rodents were captured around Yushan National Park and Alishan Forest Recreation
      Area Park in Taiwan 2,000 to 3,000 meters above sea level. Borrelia was not
      isolated from 67 small mammals of 7 species. Sera from rodents showed no positive
      reactivity against whole cell antigens of B. garinii, B. afzelii or B. valaisiana
      by ELISA. These results suggested that Lyme disease is not endemic to the Alishan
      area.

PMID- 11471828
TI  - Analysis of seawaters for the recovery of culturable Vibrio parahaemolyticus and
      some other vibrios.
AB  - We investigated the recovery of dormant and injured cells along with the normally
      culturable cells of Vibrio species with special emphasis on V. parahaemolyticus
      using both selective and non-selective media at moderate (20 C) and standard (37
      C) culture temperatures from a bay water environment. Culture temperatures (20 or
      37 C) did not affect the recovery of V. parahaemolyticus but did for other
      vibrios. We observed similar seasonality of V parahaemolyticus as in most other
      environmental studies. V. parahaemolyticus and other Vibrio species were
      recovered in higher numbers by a replica plating method compared to most probable
      number (MPN) and direct TCBS (thiosulfate citrate bile-salt sucrose) agar counts.
      Even with the replica plating method, however, vibrios number goes down to a
      minimum level and V. parahaemolyticus was undetectable during the cool
      temperature period of the year, although total bacterial cells and CFU on
      nutrient agar (with 2% NaCl) did not vary so much during the study period.

PMID- 11471829
TI  - Cytokine kinetics in the plasma of monkeys infected with pathogenic and
      nonpathogenic simian and human immunodeficiency chimeric viruses at an early
      stage of infection.
AB  - To evaluate the pattern of cytokines as a result of pathogenic and nonpathogenic
      SHIV infections in monkeys, we analyzed the cytokines interleukin (IL)-2, IL-4,
      IL-10, IL-12, and interferon (IFN)-gamma in the plasma of 8 monkeys infected with
      either pathogenic 89.6P or nonpathogenic NM-3rN chimeric viruses. The cytokine
      kinetics in the 89.6P-infected monkeys was characterized by increases of IL-2, IL
      10, and to some extent IFN-gamma and a decrease of IL-12. Although that of NM-3rN
      infected monkeys was characterized by an increase of IFN-gamma, and a transient
      decrease of IL-12. IL-4 was not detected in any of the monkeys. The results,
      therefore, showed a mixture of Th-1 and Th-2 cytokine profiles implying these
      cytokines are not clear enough to use as an index of the pathogenicity of the
      viruses at an early stage of infection.

PMID- 11471830
TI  - Effector mechanism and clinical response of BAK (BRM-activated killer) immuno
      cell therapy for maintaining satisfactory QOL of advanced cancer patients
      utilizing CD56-positive NIE (neuro-immune-endocrine) cells.
AB  - A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using
      non-MHC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral
      blood lymphocytes were selected by immobilization with anti-CD3 monoclonal
      antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were
      reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-six outpatients with
      cancer whose performance status were over 80% on Karnofsky scale were selected
      for this study. About 6 x 10(9) BAK cells were returned by intravenous drip
      infusion, at one month intervals at an outpatient clinic to each of 20 advanced
      cancer patients in whom many metastatic lesions were found postoperatively, and
      to 6 patients with no postoperatively detectable metastases. The proportion of
      CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells
      have strong cytotoxic activity and produced 20 ng/10(9) cells of beta-endorphin,
      an intracerebral hormone. During the course of BAK therapy, we adopted the Face
      scale as a QOL indicator. The QOL of all patients remained satisfactory or
      improved. Beta-endorphin is thought to make patients feel well and maintains good
      QOL because of its potent analgesic, sedative activity. From that facts that CD56
      is a neural cell adhesion molecule and a member of the Ig superfamily, and that
      the CD56-positive cell produces beta-endorphin, we concluded that the CD56
      positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell.
      Administration of BAK cells allowed all 20 advanced cancer patients with
      metastases to survive for over one year. All 6 patients receiving the same
      therapy for prevention of postoperative metastasis have been recurrence-free for
      one to five years.

PMID- 11471831
TI  - The periodic table of biology.

PMID- 11471832
TI  - Characterization of IS666, a newly described insertion element of Mycobacterium
      avium.
AB  - The insertion sequence IS666 was isolated from Mycobacterium avium strain 101.
      IS666 is a 1474 bp insertion sequence belonging to the IS256 family, that
      includes IS6120 from Mycobacterium smegmatis, IS1166 and IS1295 from Rhodococcus
      sp. IGTS8, IST2 from Thiobacillus ferrooxidans, IS256 from Staphylococcus aureus,
      and ISRm3 from Rhizobium meliloti. IS666 has 24 bp imperfect inverted repeats
      that fit the consensus described for the family, and generates 9 bp duplications
      upon insertion into the host DNA with no apparent specificity in the target
      sequence. In contrast with its two closest homologues, IS1166 and IS6120, IS666
      contains a single ORF that would codify a transposase of 434 aa. IS666 is
      restricted to M. avium, where it is present in 21% of the isolates in a number
      ranging between 1 to 7 copies.

PMID- 11471833
TI  - A minimal tiling path cosmid library for functional analysis of the Pseudomonas
      aeruginosa PAO1 genome.
AB  - Pseudomonas aeruginosa is an important pathogenic and environmental bacterium,
      with the most widely studied strain being PAO1. Using the PAO1 reference cosmid
      library and the recently completed PAO1 genome sequence, we have mapped a minimal
      tiling path across the genome using a two-step strategy. First, we sequenced both
      ends of a set of over 500 random and previously mapped clones to create a
      backbone. Second, we end-sequenced a second set of cosmid clones that were
      identified to lie within the larger gaps using hybridization of the reference
      library filters with probes designed against sequences at the center of each gap.
      The minimal tiling path was calculated using the program Domino
      (http://www.bit.uq.edu.au/download/), with the overlap between adjacent clones
      set to 5 kb (where possible) to minimize the chance of truncating genes. This
      yielded a minimal tiling cosmid library (334 clones) covering 93.7% of the genome
      in 57 contigs. This library has reduced to a workable set the number of clones
      required to represent the majority of the P. aeruginosa genome and gives the
      precise location of each cosmid, enabling most genes of interest to be located on
      clones without further screening. This library should prove a useful resource to
      accelerate functional analysis of the P. aeruginosa genome.

PMID- 11471834
TI  - MultiFun, a multifunctional classification scheme for Escherichia coli K-12 gene
      products.
AB  - An enriched classification system for cellular functions of gene products of
      Escherichia coli K-12 was developed based on the initial classification by Riley.
      In the new classification scheme, MultiFun, cellular functions are divided into
      10 major categories: Metabolism, Information Transfer, Regulation, Transport,
      Cell Processes, Cell Structure, Location, Extra-chromosomal Origin, DNA Site, and
      Cryptic Gene. These major categories are further sub-divided into a hierarchical
      scheme. Two thousand nine hundred twenty-two gene products of E. coli K-12 were
      assigned to one or more functions depending on the role they play in the cell.
      Functional assignments were made to 66% of E. coli gene products, ranging from 1
      to 16 assignments per gene product. The expansion of cellular function categories
      and the assignment to more than one category (multifunction) provides a more
      complete description of the gene products and their roles and hence better
      reflects the functional complexity of organisms. We believe this classification
      system will be useful in the field of genome analysis, both for annotation
      purposes and for comparative studies. The functional classification scheme and
      the cellular function assignments made to E. coli gene products can be accessed
      from the web at the databases GenProtEC (http://genprotec.mbl.edu) and EcoCyc
      (http://www.ecocyc.org).

PMID- 11471835
TI  - Comparative analysis of Chlamydia bacteriophages reveals variation localized to a
      putative receptor binding domain.
AB  - Three recently discovered ssDNA Chlamydia-infecting microviruses, phiCPG1,
      phiAR39, and Chp2, were compared with the previously characterized phage from
      avian C. psittaci, Chp1. Although the four bacteriophages share an identical
      arrangement of their five main genes, Chpl has diverged significantly in its
      nucleotide and protein sequences from the other three, which form a closely
      related group. The VP1 major viral capsid proteins of phiCPG1 and phiAR39 (from
      guinea pig-infecting C. psittaci and C. pneumoniae, respectively) are almost
      identical. However, VP1 of ovine C. psittaci phage Chp2 shows a high rate of
      nucleotide sequence change localized to a region encoding the "IN5" loop of the
      protein, thought to be a potential receptor-binding site. Phylogenetic analysis
      suggests that the ORF4 replication initiation protein is evolving faster than the
      other phage proteins. phiCPG1, phiAR39, and Chp2 are closely related to an ORF4
      homolog inserted in the C. pneumoniae chromosome. This sequence analysis opens
      the way toward understanding the host-range and evolutionary history of these
      phages.

PMID- 11471836
TI  - Synergetic analysis of spatio-temporal EEG patterns: Alzheimer's disease.
AB  - A spatio-temporal analysis has been employed on EEG signals recorded in groups of
      patients with Alzheimer's disease (AD). The so-called Karhunen-Loeve analysis
      method was applied to four groups of subjects: 12 patients who were diagnosed as
      having severe AD, 8 mild AD patients, 10 vascular dementia patients, and 10
      normal aged controls, to obtain the spatio-temporal eigenpatterns. The local
      difference of the global EEG pattern in mild AD patients from that of normal
      controls was expanded to the frontal regions in the case of severe AD. The
      analysis showed significant bilateral temporal functioning differences and inter
      hemispheric connection difficulty, along with remarkable intra-hemispheric
      correlation in severe AD patients. Compared to the normal controls, severe AD
      patients' brains exhibit only weak local connections and correlations, resulting
      into limited harmonious inter-hemispheric information processing. The results
      from the spatio-temporal EEG study of AD patients can be considered to be due to
      a change in the relative activity of the brain corresponding to the pathologic
      variation in AD, and the results are in accordance with reported clinical
      studies.

PMID- 11471837
TI  - Scaling behavior in beta-wave amplitude modulation and its relationship to
      alertness.
AB  - We performed an experimental study of beta waves occurring in human
      electroencephalographic signals obtained from six healthy subjects that were
      monitored during the performance of a task requiring attention to auditory
      signals. We use wavelet analysis to study whether the fluctuations in the
      modulation of the beta-wave amplitude related to an indirect measurement of
      alertness. We found that these fluctuations exhibit a power-law behavior. When
      the level of alertness dropped, the associated exponent was found to increase,
      reflecting the fact that long-range correlations grow rapidly within the system.
      We also studied the fluctuations of amplitude modulation for alpha and theta
      waves, for which we did not find a power-law behavior.

PMID- 11471838
TI  - The application of co-ordination dynamics to the analysis of discrete movements
      using table-tennis as a paradigm skill.
AB  - The purpose of this experiment was to explore the application of co-ordination
      dynamics to the analysis of discrete rather than cyclical movements. Subjects,
      standing in a fixed position, were required to return table-tennis balls
      delivered to different spatial locations in the direction of a fixed target. This
      was achieved in condition 1 by systematically scaling, from left to right and
      vice versa, the 'spatial location' of the ball-identified as a control parameter.
      In condition 2, the control condition, the spatial location was varied randomly
      over the same range. The changes between regimes of the stroke co-ordination
      pattern, defined at two different levels, (1) organisational--forehand or
      backhand drive. and (2) kinematic-the distance of the bat at ball-bat contact
      relative to the leading edge of the table, were identified as collective
      variables, the values of which changed spontaneously at the transition points
      exposed by the control parameter. The switch between regimes was shown to be
      dependent upon the direction of scaling, i.e. a hysteresis effect was identified
      in both conditions. These findings confirm that the conceptual and methodological
      frameworks of co-ordination dynamics can be applied, appropriately, to the
      analysis of discrete movements. Moreover, it would seem that control parameter
      values (spatial location of the ball) do not necessarily have to be scaled in a
      systematic way in order to produce the required effects.

PMID- 11471839
TI  - Simulating mechanical consequences of voluntary movement upon whole-body
      equilibrium: the arm-raising paradigm revisited.
AB  - Voluntary arm-raising movement performed during the upright human stance position
      imposes a perturbation to an already unstable bipedal posture characterised by a
      high body centre of mass (CoM). Inertial forces due to arm acceleration and
      displacement of the CoM of the arm which alters the CoM position of the whole
      body represent the two sources of disequilibrium. A current model of postural
      control explains equilibrium maintenance through the action of anticipatory
      postural adjustments (APAs) that would offset any destabilising effect of the
      voluntary movement. The purpose of this paper was to quantify, using computer
      simulation, the postural perturbation due to arm raising movement. The model
      incorporated four links, with shoulder, hip, knee and ankle joints constrained by
      linear viscoelastic elements. The input of the model was a torque applied at the
      shoulder joint. The simulation described mechanical consequences of the arm
      raising movement for different initial conditions. The variables tested were arm
      inertia, the presence or not of gravity field, the initial standing position and
      arm movement direction. Simulations showed that the mechanical effect of arm
      raising movement was mainly local, that is to say at the level of trunk and lower
      limbs and produced a slight forward displacement of the CoM (1.5 mm). Backward
      arm-raising movement had the same effect on the CoM displacement as the forward
      arm-raising movement. When the mass of the arm was increased, trunk rotation
      increased producing a CoM displacement in the opposite direction when compared to
      arm movement performed without load. Postural disturbance was minimised for an
      initial standing posture with the CoM vertical projection corresponding to the
      ankle joint axis of rotation. When the model was reduced to two degrees of
      freedom (ankle and shoulder joints only) the postural perturbation due to arm
      raising movement increased compared to the four-joints model. On the basis of
      these results the classical assumption that APAs stabilise the CoM is challenged.

PMID- 11471840
TI  - Complex nonlinear dynamics of the Hodgkin-Huxley equations induced by time scale
      changes.
AB  - The Hodgkin-Huxley equations with a slight modification are investigated, in
      which the inactivation process (h) of sodium channels or the activation process
      of potassium channels (n) is slowed down. We show that the equations produce a
      variety of action potential waveforms ranging from a plateau potential, such as
      in heart muscle cells, to chaotic bursting firings. When h is slowed down-
      differently from the case of n variable being slow --chaotic bursting
      oscillations are observed for a wide range of parameter values although both
      variables cause a decrease in the membrane potential. The underlying nonlinear
      dynamics of various action potentials are analyzed using bifurcation theory and a
      so-called slow-fast decomposition analysis. It is shown that a simple topological
      property of the equilibrium curves of slow and fast subsystems is essential to
      the production of chaotic oscillations, and this is the cause of the large
      difference in global firing characteristics between the h-slow and n-slow cases.

PMID- 11471841
TI  - End-point constraints in aiming movements: effects of approach angle and speed.
AB  - The present study focuses on two trajectory-formation models of point-to-point
      aiming movements, viz., the minimum-jerk and the minimum torque-change model. To
      date, few studies on minimum-jerk and minimum torque-change trajectories have
      incorporated self- or externally imposed end-point constraints, such as the
      direction and velocity with which a target area is approached. To investigate
      which model accounts best for the effects on movement trajectories of such--in
      many circumstances - realistic end-point constraints, we adjusted both the
      minimum-jerk and the minimum torque-change model so that they could generate
      trajectories of which the final part has a specific direction and speed. The
      adjusted models yield realistic trajectories with a high curvature near movement
      completion. Comparison of simulated and measured movement trajectories show that
      pointing movements that are constrained with respect to final movement direction
      and speed can be described in terms of minimization of joint-torque changes.

PMID- 11471842
TI  - Detection of enterohemorrhagic Escherichia coli in meat foods using DNA probes,
      enzyme-linked immunosorbent assay and polymerase chain reaction.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is an important cause of diarrhoea with
      blood and haemolytic uremic syndrome (HUS) in children and elderly people.
      Infections with EHEC are a world-wide public health problem, related to
      consumption of contaminated ground beef. The aim of this study was to establish
      whether different meat foods sold in Santiago, Chile pose an infection risk by
      EHEC and to evaluate three different diagnostic techniques in foods, to determine
      which is most applicable for use in Chile. A parallel analysis was performed on
      64 samples of meat foods (23 refrigerated ground meat, 23 refrigerated long pork
      sausages and 18 frozen hamburgers) sold in Santiago, Chile using DNA probes,
      enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR).
      Twenty-four samples (24 of 64 = 37.5%) were positive by DNA probes, ELISA or PCR.
      The positive and negative predictive values, sensitivity and specificity of ELISA
      were 26.7, 81.6, 30.8 and 78.4%, respectively. The positive and negative
      predictive values, sensitivity and specificity of PCR were 91.7, 96.2, 84.6 and
      98%, respectively. The EHEC serogroups most frequently isolated were O158, O157,
      O119, O125 and O114. These results show that, although molecular techniques such
      as enzyme immunoassays are useful for EHEC detection in meat foods, PCR has
      advantages in terms of sensitivity, specificity, cost and ease of implementation
      in Chile.

PMID- 11471843
TI  - Flow cytometric analysis of mitogen-induced activation of rainbow trout
      (Oncorhynchus mykiss) peripheral blood leucocytes.
AB  - Proliferation of rainbow trout peripheral blood leucocytes in vitro is usually
      assessed by measuring incorporated tritiated thymidine. In this report we
      monitored the in vitro proliferative response to the mitogen Concanavalin A (Con
      A) by means of flow cytometry (FCM) and 3H-thymidine incorporation. When analysed
      by FCM, blood leucocytes displayed two main cell populations with distinct
      forward and side scatter (FSC/SSC) characteristics: lymphocytes with low FSC/SSC
      values and non-lymphoid leucocytes (NLL) with increased FSC/SSC values. The
      nature of these cell types were confirmed by microscopy. Interestingly, the
      FSC/SSC pattern of lymphocytes remained unchanged after in vitro stimulation with
      Con A, whereas cells from the NLL population showed a marked shift towards
      increased FSC values. In stimulated cultures, the increase of FSC values of the
      NLL population significantly correlated with contemporarily measured 3H-thymidine
      incorporation (r = 0.7, P < 0.001). The mitogenic response of blood leucocytes
      originating from different individual fish varied over wide ranges. It was found
      to be related to the numbers of NLL present in the leucocyte sample. The present
      results show that qualitative and quantitative FCM analysis of morphological
      parameters (FSC/SSC) of blood leucocytes makes it possible to discriminate
      between leucocyte populations of the rainbow trout and to monitor cell
      proliferation experiments.

PMID- 11471844
TI  - A polymerase chain reaction for detection of equine herpesvirus-1 in routine
      diagnostic submissions of tissues from aborted foetuses.
AB  - Equine herpesvirus 1 (EHV-1) is the causative agent of abortion, perinatal foal
      mortality, neurological and acute respiratory diseases in horses. Conventional
      laboratory diagnosis involving viral isolation from aborted foetuses is laborious
      and lengthy and requires processing of samples within 24 h of collection, which
      is problematic for samples that come from long distances. The aim of this study
      was to develop a polymerase chain reaction (PCR) assay useful in Argentina to
      detect DNA sequences of EHV-1 in different tissues from aborted equine foetuses
      with variable quality of preservation and without the use of conventional DNA
      fenolic extraction. Several DNA extraction protocols and primers were evaluated.
      The amplification method was standardized and its specificity was analysed using
      38 foetal samples of variable quality of preservation. Of the 38 different foetal
      tissues, nine livers, six spleens and two lungs in good preservation and eight
      livers, one spleen and four lungs in a poor state of preservation were positive
      for PCR. EHV-1 was recovered only from the nine livers, five spleens and two
      lungs in good preservation. No virus was isolated from the samples that were
      poorly preserved. Viral isolation was confirmed by cytopathic effect and indirect
      immunofluorescence. The specificity of the PCR results was confirmed by the
      restriction endonuclease digestion of PCR products and hybridization.

PMID- 11471845
TI  - Epidemiological relationship of human and swine Streptococcus suis isolates.
AB  - Two cases of meningitis due to Streptococcus suis in humans are reported here. A
      butcher and an abattoir worker were referred to a health centre in Castellon
      (Spain) with fever and symptoms of meningitis. After adequate treatment, a slight
      hipoacusia persisted as sequelae in both cases. Colonies of S. suis group R,
      serotype 2 and phenotype MRP+EF+ were isolated from cerebroespinal fluid.
      Epidemiological studies showed that both workers had in common the handling of
      pork meat of slaughtered healthy pigs from three closed farms. A study of the
      tonsils from apparently healthy, slaughtered pigs was carried out. A total of 234
      tonsillar samples were obtained and 81 strains of S. suis were isolated from
      them. Serotype 2 appeared to be the most frequent (50.6%), and the analysis for
      phenotype showed a high percentage of tonsillar strains with the phenotype
      MRP+EF+ (35.9%). The humans and 28 tonsillar swine strains showed a similar
      profile (S. suis group R, serotype 2 and phenotype MRP+EF+). A total of 26 of the
      swine isolates were analysed by ribotyping using EcoRI. The human strains showed
      the same six-band hybridization pattern that shared five bands with the pattern
      most frequently shown by most of the tonsillar N. suis group R, serotype 2 and
      phenotype MRP+EF+ strains, differing only in the lightest, faintest band which
      was slightly less anodical in human (> or = 1.8 kb) than in swine (approximately
      1.8 kb). From these results, both groups of strains, humans and porcine, showed
      differences; how can these differences in the pattern of ribotyping be explained
      if they should have the same origin? Is it possible that they have undergone an
      adaptation to the new host or perhaps the modification is due to other unknown
      causes? Further studies in this area are required in order to answer these
      questions.

PMID- 11471846
TI  - Fatal gastrointestinal infection with 'Flexispira rappini'-like organisms in a
      cat.
AB  - A 4-month-old male British Blue cat with catarrhal to haemorrhagic enteritis
      showed massive colonization of the stomach, small intestine and caecum with
      spiral-shaped bacilli. In the stomach, organisms were located in foveolae and
      gland lumina and within unaltered and degenerate epithelial cells. Inflammatory
      infiltration was moderate and T cell dominated. In the intestine, bacilli were
      found in the gut lumen, berween villi, in crypt lumina and within epithelial
      cells. Degeneration of crypt epithelial cells as well as crypt dilation and
      moderate to massive macrophage-dominated infiltration of the mucosa and submucosa
      were observed. Immunohistochemically, bacilli were positive with an antibody
      against Helicobacter. Ultrastructurally, the organisms strongly resembled
      'Flexispira rappini', a spiral-shaped Helicobacter species known as a normal
      intestinal colonizer in dogs and mice.

PMID- 11471847
TI  - Hydatid echinococcosis (Echinococcus granulosus) in a laboratory colony of pig
      tailed macaques (Macaca nemestrina).
AB  - Several cases of hydatid echinococcosis were diagnosed in a laboratory colony of
      19 pig-tailed macaques (Macaca nemestrina) at the Paul Ehrlich Institute,
      Germany. Three hydatid cysts were found in the liver of an euthanized animal. The
      diagnosis of an Echinococcus granulosus infection was confirmed by histopathology
      and the results of a specific polymerase chain reaction. The serum of five of 14
      other monkeys tested for Echinococcus antibodies using a genus-specific enzyme
      linked immunosorbent assay (ELISA) was positive or weakly positive; none of the
      animals, however, showed specific reactions in a E. multilocularis-specific
      ELISA. On ultrasonographic examination, alterations in the liver were found in
      four of the serologically positive monkeys, and two animals showed clinical signs
      such as progressive anorexia, apathy and icterus. The monkeys had most probably
      acquired the E. granulosus infection in their breeding colony in Slovenia.

PMID- 11471848
TI  - Dynamics of Staphylococcus aureus infections during vaccination with an
      autogenous bacterin in dairy cattle.
AB  - The effect of an autogenous vaccine against Staphylococcus aureus on S. aureus
      prevalence and mastitis, as well as on somatic cell count (SCC), was studied in a
      dairy herd with a high prevalence of S. aureus. The vaccination group (n = 35; 22
      cows and 13 heifers) and the control group (n = 36; 23 cows and 13 heifers)
      received the vaccine or a placebo, respectively, according to the following
      protocol: all animals: basic immunization (twice, 3 weeks apart); cows: booster
      dose at the time of drying off, 5 and 2 weeks before calculated calving date;
      heifers: booster dose 2 and 5 weeks before calculated calving date. The vaccine
      or the placebo was administered subcutaneously in the area of the supramammary
      lymph nodes. Quarter milk samples were collected monthly and subjected to SCC and
      bacteriological evaluation. At this time, the animals were also checked for signs
      of clinical mastitis. Non-clinical S. aureus mastitis diagnoses were based on
      udder quarter SCC and a positive S. aureus culture. In order to compare the SCC
      in individual whole milk samples, records from the monthly milk quality testing
      were evaluated. Cow and udder quarter prevalence of S. aureus intramammary
      infections calculated for the experimental animals and quarters, respectively,
      did not differ between groups. However, during the lactation period following the
      boostcr dose, the prevalence of S. aureus increased in both groups (P < 0.05).
      The cumulative incidence of various mastitis diagnoses (clinical, subclinical,
      latent infection) due to S. aureus on an animal basis did not differ between
      groups. On an udder quarter basis, the cumulative incidence of subclinical
      mastitis was higher in vaccinated animals than in control animals (33.8 versus
      26.0%; P < 0.05). This was mainly due to a higher cumulative incidence of
      subclinical mastitis in vaccinated than control heifers. The SCC in composite
      milk samples did not differ between groups, but increased as lactation
      progressed. The herd prevalence of S. aureus differed considerably throughout the
      study period, but declined consistently to below 10% at the end of the study
      period. Recent herd checks revealed a prevalence of S aureus infections of < 5%.
      It is concluded that the autogenous bacterin tested in this study did not have
      the desired effect on the prevalence of S. aureus infections and mastitis or SCC.
      The decline in S. aureus prevalence was very probably due to other factors than
      specific immunization against S. aureus.

PMID- 11471849
TI  - Severe enteric disease in an animal shelter associated with dual infections by
      canine adenovirus type 1 and canine coronavirus.
AB  - An outbreak of dual infection in dogs with canine adenovirus type 1 (CAV-1) and
      canine coronavirus (CCV) infection is reported in an animal shelter that
      comprised approximately 200 adults stray dogs and 30 puppies. Twenty puppies died
      7-8 days after the onset of the clinical signs (severe enteritis, leucopoenia,
      respiratory distress and dehydration). Both CAV-1 and CCV were isolated from
      tissue or swab samples. Antibodies to CCV and, at high levels, to CAV-1 also were
      detected in several puppies. The principal histological findings were atrophy of
      small intestinal villi, lymphoid depletion, hepatitis and bronchopneumonia. The
      persistence of CCV in the faeces, observed by the polymerase chain reaction
      assay, was longer than previously reported. Results demonstrated the serious
      consequences which may occur with dual infections by CAV-1 and CCV in assembled
      groups of dogs that are housed in poorly managed kennels with inadequate
      vaccination programmes.

PMID- 11471850
TI  - Comparison of 16 chelonid herpesviruses by virus neutralization tests and
      restriction endonuclease digestion of viral DNA.
AB  - A total of 16 chelonid herpesviruses that were isolated between 1992 and 1998
      were compared with one another on the basis of serology and restriction enzyme
      digestion patterns of viral DNA. The viruses stem from tortoises of three
      different species in four different European countries and the United States of
      America. The majority of the isolates were similar to one another. One isolate,
      however, differed strongly from all others both serologically and in the
      restriction cleavage pattern of its DNA, showing that there are at least two
      different sero- and genotypes of herpesviruscs that infect tortoises.

PMID- 11471851
TI  - A randomized comparison of triple therapy Helicobacter pylori eradication
      regimens in children with peptic ulcers.
AB  - An open, randomized trial was performed to compare the efficacy of three
      Helicobacter pylori eradication regimens in children with peptic ulcer disease. A
      total of 106 children (5 - 15 years) were treated for 1 week with metronidazole,
      30 - 40 mg/kg per day depending on age, amoxycillin, 750 mg/day, and one of three
      anti-secretory agents: proprietary omeprazole, 20 - 40 mg/day depending on age;
      generic omeprazole, 20 - 40 mg/day; or ranitidine, 150 mg twice daily. The H.
      pylori eradication rate was significantly higher in patients receiving
      proprietary omeprazole (88.9%) than in those receiving generic omeprazole (80.0%)
      or ranitidine (74.3%), and this was associated with a trend towards faster ulcer
      healing. It is concluded that triple therapy consisting of an anti-secretory
      agent and two antimicrobials produces effective eradication of H. pylori and
      ulcer healing in children with peptic ulcer disease, and that proprietary
      omeprazole is more effective than both ranitidine and the generic formulation
      used in this study.

PMID- 11471852
TI  - A randomized, double-blind, parallel-group study to compare the anti-hypertensive
      effects of imidapril and nifedipine in the treatment of mild-to-moderate
      essential hypertension.
AB  - This 12-week, multicentre, double-blind, placebo-controlled, parallel-group study
      compared efficacy of the angiotensin-converting enzyme (ACE) inhibitor imidapril
      5 - 10 mg/day and the calcium channel blocker nifedipine slow-release (SR)
      formulation 20 - 40 mg twice daily. In total 320 patients aged 18 - 75 years,
      with mean sitting diastolic blood pressures of 95 - 115 mmHg, were randomized to
      treatment with imidapril (n = 157) or nifedipine SR (n = 163). Efficacy
      evaluations were based on the intent-to-treat principle. On study completion,
      there was no difference between the groups with respect to the primary efficacy
      variable of response to treatment (imidapril 63.1%; nifedipine SR 61.3%). After 2
      weeks' treatment, clinically relevant decreases in blood pressure were observed
      in both groups, with a trend towards further reductions until study end. Fewer
      patients in the imidapril-treated group than the nifedipine group withdrew due to
      adverse events that occurred on treatment with study medication (3.2% versus
      16.0%) or experienced adverse events (40.1% versus 49.7%). In addition, fewer
      adverse events were causally related to imidapril (24.2%) compared with
      nifedipine SR (41.7%). These results show that imidapril is effective in the
      treatment of essential hypertension and is better tolerated than nifedipine SR.

PMID- 11471853
TI  - A double-blind comparative study of zolpidem versus zopiclone in the treatment of
      chronic primary insomnia.
AB  - Zolpidem (10 mg/day) and zopiclone (7.5 mg/day), administered at night, were
      compared in a 14-day, double-blind, equivalence trial on 479 chronic primary
      insomniacs (zolpidem, 231; zopiclone, 248) throughout Japan, with a 1-week follow
      up to assess rebound. The primary endpoint was the investigators' rating of
      global improvement of sleep disorders. A total of 32 patients in the zolpidem
      group (13.9%) and 45 patients in the zopiclone group (18.1%) withdrew from the
      study before the end of the treatment. In the zolpidem group, 67.9% (142/209) of
      patients were rated at least 'moderately improved' versus 61.6% (135/219) with
      zopiclone, zolpidem being at least as effective as zopiclone (90% confidence
      interval: -1.7, 14.3). With zolpidem, sleep onset latency improved in
      significantly more patients (85.8% versus 77.5%) and significantly fewer patients
      showed aggravated sleep onset latency relative to baseline at follow-up (4.5%
      versus 15.4%). Significantly fewer patients receiving zolpidem experienced drug
      related adverse events (31.3% versus 45.3%), with bitter taste representing 5.8%
      (six of 104) of such complaints with zolpidem compared with 39.9% (69/173) with
      zopiclone. In conclusion, zolpidem was at least as effective as zopiclone, showed
      significantly less rebound on discontinuation and was better tolerated.

PMID- 11471854
TI  - Effects of eradication therapy on gastric emptying in patients with Helicobacter
      pylori-positive duodenal ulcers.
AB  - In this study 28 patients with Helicobacter pylori-positive duodenal ulcers were
      treated with a 7-day triple-therapy regimen (omeprazole, clarithromycin,
      amoxycillin). Gastric emptying time was measured scintigraphically before and
      after therapy. Only 13 patients attended regularly for their endoscopic and
      scintigraphic follow-ups. Gastric emptying time was 57.6+/-16.5 min in 28
      patients before therapy, and 44.4+/-13.9 min after therapy (44.7+/-7.9 min in the
      control group). The present study demonstrated gastric emptying time to be longer
      in the ulcer patients compared with healthy controls and that, after eradication
      therapy, gastric emptying time became almost normal in the ulcer patients.

PMID- 11471855
TI  - Micronutrient status and glutathione peroxidase in bedridden patients on tube
      feeding.
AB  - Deficiency of micronutrients, especially selenium, is common in critically ill
      patients. We investigated the micronutrient status (selenium, zinc, copper and
      manganese) and glutathione peroxidase (GSH-Px) activity in 30 tube-fed patients
      and 21 hospitalized non-tube-fed control patients. Serum levels of selenium,
      copper and manganese in tube-fed patients were significantly lower than in
      control patients (selenium: 4.85+/-1.38 microg/dl versus 8.67+/-1.45 pg/dl;
      copper: 44.7+/-36.9 microg/dl versus 92.1+/-21.2 microg/dl; manganese 0.59+/-0.41
      microg/dl versus 1.52+/-0.59 microg/dl). However, zinc and log GSH-Px in the
      serum were similar in the two groups. Serum selenium concentration correlated
      with the daily intake of selenium in tube-fed patients, but zinc, copper and
      manganese concentrations did not correlate with the daily intake of the
      respective trace elements in tube-fed patients. Blood GSH-Px activity correlated
      positively with serum selenium concentrations in the control patients, but not in
      tube-fed patients. These results demonstrate that selenium content of enteral
      feed appears to be insufficient to maintain normal serum levels in elderly
      bedridden patients. Our findings emphasize the importance of monitoring
      micronutrient status in patients on enteral feeding to avoid trace element
      deficiencies.

PMID- 11471856
TI  - Schedule-dependent combined sensitivity testing of anti-cancer agents in human
      gastric carcinoma cell lines.
AB  - The efficacy of combination chemotherapy for gastric carcinoma has been
      unsatisfactory, although the prognosis of advanced and recurrent disease has
      improved with the introduction of cisplatin (CDDP). This study examines the
      effect of the anti-cancer therapies CDDP, doxorubicin (ADM) and etoposide (VP-16)
      on the cell cycle and their cytotoxicity against two gastric carcinoma cell
      lines: MKN-28 (well differentiated) and MKN-45 (poorly differentiated). The
      treatments have different cytocidal mechanisms, and they were studied in dual
      combinations. For all combinations studied, cytotoxicity against MKN-45 was
      higher than against MKN-28. For ADM plus CDDP, or ADM plus VP-16, cytotoxicity
      was higher in patients pretreated with ADM than other regimens. The highest anti
      tumour activity against both cell lines was obtained with ADM followed by CDDP
      (we have obtained good clinical results with this regimen). Schedule-dependent
      combined sensitivity testing of anti-cancer agents will be useful for the
      clinical application of therapies.

PMID- 11471857
TI  - Varicella zoster virus antigens in the epidermis of patients with herpes zoster
      before and after treatment with acyclovir: an immunohistochemical study.
AB  - Using a monoclonal antibody to varicella zoster virus (VZV), an
      immunohistochemical study was performed before and after treatment with acyclovir
      (750 mg/day intravenously for 5 - 7 days) to investigate the distribution of VZV
      antigens in the epidermis of four in-patients with herpes zoster, and to
      correlate their presence with clinical manifestations of the disease. Biopsy
      specimens were obtained from epidermal lesions on admission to hospital prior to
      acyclovir administration, and again following treatment. In all cases, VZV
      antigens were found extensively in the erythematous and vesicular lesions before
      treatment, but they were not detected 5 - 7 days later in the ulcerative, crusted
      or pigmented lesions after acyclovir therapy. Further controlled studies will be
      necessary to compare the distribution of epidermal VZV antigens in acyclovir
      treated patients with that in a placebo group to determine whether the loss of
      VZV antigens was due to acyclovir or to a natural decrease over time.

PMID- 11471858
TI  - DNA demethylase expression correlates with lung resistance protein expression in
      common epithelial ovarian cancers.
AB  - We examined DNA demethylase (dMTase) expression, a common feature of ovarian
      cancer, to establish if there is any relationship between gene expression and
      disease stage, histopathology and survival. We also sought evidence of concurrent
      dMTase and lung resistance protein (LRP) expression. In 43 epithelial ovarian
      cancers studied we found that the relative strength of gene expression correlated
      with disease stage, histology and survival. dMTase expression was positive in
      38/43 cases studied (88.4%). We also identified a significant correlation between
      dMTase and LRP expression. In 80% of cases where dMTase was not expressed, LRP
      was not found. Conversely, 70% of cases where dMTase expression was positive were
      also LRP-positive. We also identified a weak trend indicating that dMTase
      expression may occur more frequently in cases of endometrioid and serous
      adenocarcinoma. The expression of dMTase is a common feature of ovarian cancer
      and there is a correlation between dMTase and LRP expression, suggesting that
      there may be an epigenetic upregulation of the gene.

PMID- 11471859
TI  - Immunomodulation based on a two-way paradigm with deoxyspergualin alleviates
      graft-versus-host reaction in small-bowel transplantation in rats.
AB  - In this study, we investigated whether or not deoxyspergualin used as donor
      pretreatment, with and without pretreatment using bone-marrow-cell injection,
      could alleviate graft-versus-host reaction (GVHR) following small-bowel
      transplantation in an unidirectional GVHR model with Lewis (LEW)-to-F1 rats. In
      addition, we studied the effect of deoxyspergualin plus bone-marrow-cell donor
      pre-operative treatment in combination with recipient postoperative treatment
      using deoxyspergualin. When the donor was pretreated with bone-marrow cells from
      recipient rats, the recipient died at 7.2+/-1.4 days, showing significantly
      shorter survival compared with the control group. Deoxyspergualin, when employed
      either alone as recipient post-treatment or as donor pretreatment, both with and
      without additional pretreatment with F1 recipient bone-marrow-cell injection, did
      not result in significant prolongation of recipient survival. The combination of
      donor pretreatment with deoxyspergualin plus F1 bone-marrow-cell injection
      followed by post-operative deoxyspergualin administration, however, resulted in
      significant prolongation in recipient survival compared with control (26.1+/-1.7
      days). In addition, no severe cutaneous lesions on GVHR were seen throughout the
      observation period. This suggests that donor pretreatment with deoxyspergualin
      and recipient bone-marrow-cell injection combined with postoperative
      deoxyspergualin administration can lead to resistance to GVHR after parent-to-F1
      small-bowel transplantation.

PMID- 11471860
TI  - Graft-versus-host reaction in small-bowel transplantation and possibilities for
      its circumvention.
AB  - To study graft-versus-host reaction (GVHR) in small-bowel transplantation and its
      underlying mechanisms and to find methods for circumventing GVHR, we used an
      unidirectional GVHR model in which F1 Lewis (LEW) x Wistar King A (WKA) hybrid
      rats received small-bowel transplants from either LEW or WKA parent rats. The
      survival time of F1 hybrid rats that received full-length small-bowel
      transplantation from LEW and WKA was 16.3+/-2.1 days and 18.2+/-3.4 days,
      respectively. When one-quarter of LEW small bowel was transplanted to an F1
      hybrid recipient, the survival time was significantly longer at 44.0+/-23.4 days
      compared with rats that had received full-length LEW small-bowel transplantation.
      The survival time of F1 hybrid rats which received an injection of high-dose (5 x
      10(8) cells) LEW or WKA spleen cells was 11.9+/-4.0 days and 13.1+/-3.6 days,
      respectively. However, when an injection containing a low dose (1 x 108 cells) of
      LEW spleen cells was used, survival was > 100 days, showing significance compared
      with the survival of rats receiving the higher dose LEW spleen-cell injection.
      Both small-bowel transplantation and spleen-cell injection were compared for the
      effective period of recipient resistance to donor cell or small-bowel
      transplantation as second challenge. When the F1 rats given a quarter LEW small
      bowel transplant as first challenge were treated with a high-dose of spleen cells
      30 days after transplantation, they survived for > 30 days without GVHR. F1 rats
      that were treated with a low-dose LEW spleen-cell injection, followed 30 days
      later by full LEW small-bowel transplantation, had a survival time of > 100 days.
      These results indicate that segmental small-bowel transplantation and spleen-cell
      injection as first challenge may facilitate the prevention of GVHR, resulting in
      resistance to subsequent immunological challenge.

PMID- 11471861
TI  - Effect of AA-2414 on early and late bronchial responses in actively sensitized
      guinea-pigs.
AB  - The effect of a new thromboxane A2 receptor antagonist, AA-2414, (+/-)-7-(3,5,6
      trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid, on dual
      bronchoconstriction and airway hyper-reactivity in actively sensitized guinea
      pigs was investigated. Immediate and late bronchial responses were seen 1-10 min
      and 4-7 h, respectively, after inhalation of antigen. In guinea-pigs pretreated
      with AA-2414, 5 mg/kg orally, the immediate bronchial response was inhibited. An
      administration of AA-2414 inhibited the late bronchial response. The numbers of
      eosinophils, neutrophils and macrophages, but not of lymphocytes, in
      bronchoalveolar lavage fluid were increased at 4 h after antigen inhalation. AA
      2414 did not affect the numbers of total cells, eosinophils, neutrophils or
      macrophages. Sensitized guinea-pigs showed a significant airway hyperreactivity
      to inhaled histamine, which was not influenced by an administration of AA-2414.
      Luminol-dependent chemiluminescence of airway-infiltrated cells from sensitized
      guinea-pigs stimulated with A23187 was slightly inhibited by AA-2414. These
      results show that AA-2414 inhibits the late asthmatic response and the production
      of oxygen radicals from airway-infiltrated cells.

PMID- 11471862
TI  - Review of orthostatic tests on the safety of tamsulosin, a selective alpha1A
      adrenergic receptor antagonist, shows lack of orthostatic hypotensive effects.
AB  - Two phase III studies with tamsulosin, a selective alpha1A-adrenergic receptor
      antagonist, were conducted to evaluate the safety and efficacy of the standard
      treatment doses of 0.4 mg/day and 0.8 mg/day in patients with symptoms of benign
      prostatic hyperplasia (BPH). These large-scale clinical trials were the first to
      include extensive testing for possible drug-induced orthostatic hypotension (OH).
      The frequency of positive orthostatic tests and magnitude of vital sign changes
      were compared among tamsulosin and placebo-treated groups. The results indicate
      that tamsulosin up to 0.8 mg/day does not induce higher risk of OH than that of
      placebo. Data from post-marketing surveillance (PMS) studies of tamsulosin
      indicate that the incidence of hypotension and syncope is extremely low in
      community-dwelling elderly men treated for BPH. From the results of the phase III
      studies, PMS studies and an active-controlled clinical pharmacology study, we
      conclude that the orthostatic test is a useful and convenient method to evaluate
      the risk of OH and syncope during the investigational stage.

PMID- 11471863
TI  - Intravenous immunoglobulin in adult varicella pneumonia complicated by acute
      respiratory distress syndrome.
AB  - Pneumonia is a rare but serious complication of varicella in adults. We report a
      case of a previously healthy 32-year-old man with varicella pneumonia that was
      complicated by acute respiratory distress syndrome. He was treated successfully
      with acyclovir and intravenous immunoglobulin in addition to mechanical
      ventilation. We conclude that intravenous immunoglobulin, in combination with
      acyclovir, is a safe and probably effective therapy for adult varicella pneumonia
      that is complicated by acute respiratory distress syndrome.

PMID- 11471864
TI  - Mercury exposure in utero and during infancy.
AB  - Mercury in blood samples was speicated from mothers and their infants up to 2 mo
      after delivery. There were significant correlations between umbilical cord blood
      and maternal blood for methylmercury (MeHg) and inorganic mercury (I-Hg) levels.
      The MeHg levels in cord blood were significantly higher than in maternal blood,
      while I-Hg levels were significantly higher than in maternal blood, while I-Hg
      levels were about the same. The maternal MeHg and I-Hg levels remained stable
      during the sampling period, whereas the MeHg concentration in infant blood
      decreased more than 45% between the 72-h and 2 mo sampling times. The I-Hg levels
      in infant blood were low at birth, and remained low during the sampling period.
      The results of the present study do not support I-Hg absorption through milk as a
      significant source of exposure. However, the number of observations is small, and
      a larger study is warranted in order to verify the data.

PMID- 11471865
TI  - Urinary cadmium elimination as a biomarker of exposure for evaluating a cadmium
      dietary exposure--biokinetics model.
AB  - The Cadmium Dietary Exposure Model (CDEM) utilizes national survey data on food
      cadmium concentrations and food consumption patterns to estimate dietary intakes
      in the U.S. population. The CDEM has been linked to a modification of the cadmium
      biokinetic model of Kjellstrom and Nordlberg (KNM) to derive predictions of
      kidney and urinary cadmium that reflect U.S. dietary cadmium intake and related
      variability. Variability in dietary cadmium intake was propagated through the KNM
      using a Monte Carlo approach. The model predicts a mean peak kidney cadmium
      burden of approximately 3.5 mg and a 5th-95th percentile range of 2.2-5.1 mg in
      males. The corresponding peak renal cortex cadmium concentration in males is 15
      microg/g wet cortex (10-22, 5th-95th percentile). Predicted kidney cadmium levels
      in females were higher than males: 5.1 (3.3-7.6) mg total kidney, 29 (19-43)
      microg/g wet cortex. Predicted urinary cadmium in males and females agreed with
      empirical estimates based on the NHANES III, with females predicted and observed
      to excrete approximately twice the amount of cadmium in urine than males. An
      explanation for the higher urinary cadmium excretion in females is proposed that
      is consistent with the NHANES III data as well as experimental studies in humans
      and animals. Females may absorb a larger fraction of ingested dietary cadmium
      than males, and this difference may be the result of lower iron body stores in
      females compared to males. This would suggest that females may be at greater risk
      of developing cadmium toxicity than males. The predicted 5th-95th percentile
      values for peak kidney cadmium burden are approximately 60% of the peak kidney
      burden (8-11 mg) predicted for a chronic intake at the U.S. Environmental
      Protection Agency (EPA) chronic reference dose of 1 microg/kg-d.

PMID- 11471866
TI  - Oral bioaccessibility of trivalent and hexavalent chromium in soil by simulated
      gastric fluid.
AB  - Chromium is found in soil from natural sources and anthropogenic activities. The
      ingestion of soil contaminated with chromium especially by children can have
      toxic consequences. Therefore, it is important to quantify the oral
      bioaccessibility of chromium in chromium in contaminated soil. In this study,
      chromium-51 as chromic (III) chloride and sodium chromate (VI), was mixed with an
      Atsion sandy soil and a Keyport clay soil and stored for 4 mo at either 21-25
      degrees C or 2-4 degrees C. Utilizing simulated gastric conditions, the oral
      bioaccessibility of chromium in soil was determined. When the effects of soil on
      the bioaccessibility of chromium were compared, the data revealed the the
      bioaccessibility of chromium (III) from the clay soil was significantly lower
      than from the sandy at 21-25 degrees C. However, at 2-4 degrees C, more chromium
      (III) was extracted by synthetic gastric fluid from the clay soil than from the
      sandy soil. Temperature was also a factor as evidenced by the higher
      bioaccessibility of chromium (IV) in the sandy soil at 2-4 degrees C and of both
      chromium species in the clay soil at the same temperature. Reduction of the
      soluble chromium (VI) chemical to the nonsoluble chromium (III) compound in the
      acidic soils by naturally occurring organic matter in soil would explain the
      lower bioaccessibilty of chromium (VI) at 21-25 degrees C. At 2-4 degrees C, the
      data indicate that the rate of chromium (VI) reduction to chromium (III) was
      slowed. Although the results of this study are limited to one low concentration
      of chromium (III) and chromium (VI)  and indicate that the bioaccessibility of
      chromium in soil can range between 18% and 72%, the data also suggest that there
      may be a potential health hazard from oral exposure to chromium in heavily
      contaminated sites. Therefore, more extensive research should be conducted to
      determine if thes findings can be extended to environmentally relevant
      concentrations.

PMID- 11471867
TI  - Effects of creosote exposure on rainbow trout pronephros phagocyte activity and
      the percentage of lymphoid B cells.
AB  - An outdoor microcosm study was conducted in order to evaluate the kinetics of
      immunomodulation in rainbow trout (Oncorhynchus mykiss) exposed to liquid
      creosote. Fish were sampled on d 7, 14, 21, and 28 from microcosms dosed
      initially with 0, 3, and 10 microl/L of creosote. Pronephros leukocytes were
      monitored for phagocytic activity, oxidative burst, and surface immunoglobulin
      positive (Slg+) B-cell counts. Oxidative burst was inhibited by creosote
      exposure; however, by sampling d 28, the burst response returned to near control
      levels. Phagocytic activity, on the other hand, was stimulated, peaking on
      sampling d 7, then returning to near control levels by d 28. Although control
      Slg+ B-cell counts were quite variable across sampling days, Slg+ B-cell counts
      were also elevated in creosote-exposed fish after seven days of exposure. Slg+ B
      cell numbers decreased significantly to near control levels during the remainder
      of the study. The overall results from this study confirm that creosote has the
      potential to alter certain immune parameters, and emphasize the importance of
      monitoring changes in the immune system during exposure. Polycyclic aromatic
      hydrocarbons (PAHs), a major constituent of liquid creosote, are the suspected
      immune-altering agents.

PMID- 11471868
TI  - Stewardship and future land use at a Department of Energy site: does self
      interest determine ratings?
AB  - Based on studies at several Department of Energy sites and Superfund sites, as
      well as elsewhere, it is clear that people prefer that contaminated lands be
      restored to usable land. Knowing the future uses for such land can inform
      environmental cleanup and restoration decision making, often determining the
      level of cleanup, costs, future management, and stewardship. This article
      examines the relationship between general environmental attitudes, future land
      use preferences, and recreational activities for people living around the
      Department of Energy's Savannah River Site in South Carolina. There were few
      differences in the rating for general environmental problems as a function of
      recreational activities. Although future land use ratings were generally
      correlated with the number of days people engaged in particular activities
      (hunting, fishing, hiking, camping), people who hunted and fished rated nearly
      every recreational activity higher than did people who only camped or hiked, or
      than those who engaged in no outdoor activities. Thus, campers and hikers did not
      rate camping and hiking higher as future land uses than did other groups. These
      data suggest that there is widespread support for recreational activities as
      future uses for the Savannah River Site, regardless of whether people participate
      in them or not, and that current cleanup and stewardship decisions should
      consider these views.

PMID- 11471869
TI  - Insulin-like growth factor 1 measurement in diagnosis and management of
      acromegaly.
AB  - This article discusses the characteristic features of growth hormone secretion
      and insulin-like growth factor I (IGF-1) concentrations both in patients with
      acromegaly and in normal subjects. The therapeutic options for the treatment of
      acromegaly are briefly discussed, as are the current definitions of successful
      therapy. The article focuses on the use of serum and urinary growth hormone
      measurements along with the current and potential use of serum IGF-1, both at
      diagnosis and during long-term follow-up.

PMID- 11471870
TI  - The ischaemic lactate-ammonia test.
AB  - The ischaemic lactate-ammonia test is widely used for investigating patients with
      muscle pain and fatigue. It involves measuring plasma lactate and ammonia
      produced as a result of forearm exercise under ischaemic conditions in a fasted
      subject. Its clinical use is to screen patients with muscle complaints for
      disorders of carbohydrate metabolism, in particular to identify those in whom
      further investigation may provide useful diagnostic information. There is a wide
      variety of methods described, reflecting attempts to optimize the response and
      hence the diagnostic value of the test. Although it is often considered a general
      screening test for metabolic muscle disease, the situations in which it is useful
      are specific. Here we review the use of the test and present the results of an
      audit of its use in our departments.

PMID- 11471871
TI  - Biochemical analysis of pleural fluid: what should we measure?
AB  - Biochemical examination of pleural fluid is usually done to try to identify the
      cause of a pleural effusion. The various analytes that have been suggested for
      this are reviewed and evaluated. Distinguishing whether the effusion is an
      exudate or transudate is a pragmatic first step. with further investigations
      dictated by the clinical features and these results. Total protein and lactate
      dehydrogenase were used first; Light's criteria were published in 1972 and since
      then additional markers including cholesterol, bilirubin and albumin gradient
      plus combinations of these have been proposed. Although combination testing does
      improve the sensitivity for diagnosis of an exudate. this is at the expense of
      specificity. Measurement of fluid to serum ratios appears to confer no advantage,
      and if a single test is required total protein performs as well as any.
      Additional tests may be useful in specific circumstances: pleural fluid pH may
      aid decisions over drainage of a parapneumonic effusion; glucose may indicate an
      effusion associated with rheumatoid arthritis; and adenosine deaminase may help
      with the diagnosis of tuberculous effusions.

PMID- 11471872
TI  - Relationships between serum (ZZ)-bilirubin, its subfractions and biliverdin
      concentrations in infants at 1-month check-ups.
AB  - In 150 infants, including those with breast milk jaundice, who were brought to
      our hospital for their 1-month check-ups, the serum concentrations of (ZZ)
      bilirubin, its subfractions and biliverdin were measured by high-performance
      liquid chromatography and the relationships among them investigated. (ZZ)
      Bilirubin was found to have the highest serum concentration, followed by (ZE)
      bilirubin, accounting for 14.0 (geometric mean) % of (ZZ)-bilirubin. Biliverdin
      had a serum concentration of 0.95% of (ZZ)-bilirubin. There was only a small
      amount of total (di- and mono-) glucuronosyl bilirubin, 0.42% of (ZZ)-bilirubin.
      (ZE)-Bilirubin, (EZ)-bilirubin, (EZ)-cyclobilirubin. biliverdin, diglucuronosyl
      bilirubin and monoglucuronosyl bilirubin (C-8 and C-12) showed positive
      logarithmic correlations with (ZZ)-bilirubin (R2=0.16 or above, P<0.05). (ZE)
      Bilirubin showed a significant positive logarithmic correlation with (ZZ)
      bilirubin (R2=0.863, P<0.0001). Furthermore, (EZ)-cyclobilirubin, the most
      important photoisomer in phototherapy for neonatal hyperbilirubinaemia, was
      detected in very small amounts in approximately half of the neonates (84 of 150)
      when they were in conditions of only weak ambient light. The relationship between
      total glucuronosyl bilirubin and (ZZ)-bilirubin concentrations fitted a model of
      saturation kinetics of bilirubin UDP-glucuronosyltransferase.

PMID- 11471873
TI  - Reference intervals for thyroid hormones in pregnant Chinese women.
AB  - OBJECTIVE: To establish gestation-related reference intervals for thyroid
      hormones in a Chinese population. MATERIALS AND METHODS: A prospective study with
      343 healthy pregnant women (5-41 weeks) and 63 non-pregnant controls. Thyroid
      stimulating hormone (TSH), free thyroxine (T4) and tri-iodothyronine (T3) (and
      human chorionic gonadotrophin) were measured by immunoassays. The median, 2.5th
      and 97.5th percentiles at 4-week intervals were calculated. Data were also
      analysed for significant trends using ANOVA. RESULTS: Free T3 decreased during
      pregnancy, whereas free T4 initially increased, peaking between 9-13 weeks and
      then decreased, the decline becoming significant by week 21. TSH mirrored changes
      in free T4. CONCLUSION: The gestation-related reference intervals for thyroid
      hormones should alleviate the misinterpretation of thyroid function in pregnancy.

PMID- 11471874
TI  - A simple high-pressure liquid chromatography cotinine assay: validation of
      smoking status in pregnant women.
AB  - Smoking during pregnancy is a significant public health issue, and studies of the
      effectiveness of interventions to reduce maternal smoking require accurate
      measurement of smoking status. This study addresses some key issues in
      improvement of the effectiveness and efficiency of chemical validation of smoking
      status using a simplified high-pressure liquid chromatography urine cotinine
      method. Urine samples were collected from pregnant women enrolled in a smoking
      cessation trial and from non-pregnant volunteers exposed to environmental tobacco
      smoke (ETS). Analysis of ETS samples produced a maximum cotinine of 28
      microg/mmol creatinine, which was established as the cut-off point for this
      method. This method is a relatively fast and inexpensive technique with which to
      analyse large batches of cotinine samples and can reliably measure smoking
      status.

PMID- 11471875
TI  - Analysis of 4-methylthioamphetamine in clinical specimens.
AB  - There has been much publicity, particularly in Europe, regarding a new
      phenylethylamine-based compound called 4-methylthioamphetamine (4-MTA), also
      known as para-methylthioamphetamine (p-MTA), MTA or 'Flatliner'. Chemically, 4
      MTA is an amphetamine derivative and is a potent, non-neurotoxic serotonin
      releasing agent and reversible inhibitor of rat monoamine oxidase-A. Its effects,
      therefore, appear different from those of amphetamine. Analysis of various plasma
      and urine specimens in three clinical cases implicating 'Ecstasy' ingestion
      revealed the presence of 4-MTA. Presumed metabolites were also detected, with one
      compound identified as being 4-MTA sulphoxide. The concentrations of 4-MTA
      measured in the plasma ranged from 0.131 mg/L to 0.760 mg/L. In one patient the 4
      MTA concentration was determined in a series of plasma samples and this allowed a
      presumptive half-life of approximately 7 h to be estimated. This paper describes
      the first reported data regarding possible pharmacokinetics of 4-MTA in humans
      and presents the first reported non-fatal instances of 4-MTA intoxication in the
      UK.

PMID- 11471876
TI  - Synthetic peptide-based electrochemiluminescence immunoassay for anti-Borna
      disease virus p40 and p24 antibodies in rat and horse serum.
AB  - Borna disease virus (BDV) is a neurotropic pathogen that infects a wide variety
      of vertebrates. We have developed a new electrochemiluminescence immunoassay
      (ECLIA) for the detection of antibodies to BDV, using three synthetic peptides
      corresponding to the amino acid residues 3-20 and 338-358 of p40 and 59-79 of p24
      peptide of BDV. Using the ECLIA, we examined serum samples for the presence of
      anti-BDV antibodies in 20 rats (experimentally BDV-infected and uninfected) and
      38 horses (13 US horses, experimentally infected and uninfected, and 25 Japanese
      horses, feral and domestic). The ECLIA, performed in a double-blind manner,
      detected anti-BDV antibodies in rats with a history of BDV infection, giving
      results that were in agreement with indirect immunofluorescence assay and/or
      Western blot (WB) analysis. The ECLIA also correctly identified all three
      experimentally infected horses and four domestic American horses that were
      seropositive for BDV antibodies by WB. Among the Japanese horses, at least two
      out of 10 feral and six out of 15 domestic horses were seropositive for BDV. In
      most of these cases, the specificity of immunoreactivity was verified by blocking
      with soluble p40 and p24 peptides.

PMID- 11471877
TI  - Evaluation of specific high-performance liquid-chromatographic determinations of
      urinary adrenaline and noradrenaline by comparison with isotope dilution mass
      spectrometry.
AB  - A method for the determination of metadrenaline (MA), normetadrenaline (NMA) and
      3-methoxytyramine (3-MT) in human urine using high-performance liquid
      chromatography followed by electrochemical detection (ECD) was validated
      primarily by comparing the results with those obtained by a gas chromatography
      mass spectrometry (GC-MS) reference method. Correlation coefficients of 0.93,
      0.94 and 0.91 were obtained for MA, NMA and 3-MT, respectively, in a group of
      healthy controls consisting of 30 women and 30 men. A systematic difference was
      detected only for 3-MT (-16%). Further tests of accuracy (linearity and recovery)
      and precision demonstrated that the described method must be considered to be a
      reliable approach to assess urinary metadrenalines in the diagnosis of
      phaeochromocytoma. At lower concentrations (MA, 248 nmol/L; NMA, 434 nmol/L; 3
      MT, 402 nmol/L), within-assay coefficients of variation were close to 5% or less
      (5.3, 4.6 and 2.2%, respectively) and between-assay coefficients of variation
      were 8.9, 11.2 and 12.3%, respectively, for the same low levels. This raises the
      possibility that this method can also be applied to assess urinary free,
      unconjugated metanephrines. Sex differences were detected for MA and NMA
      excretion when expressed in nmol per 24 h and nmol/mmol creatinine, respectively,
      by both ECD and GC-MS methods.

PMID- 11471878
TI  - Measurement of pancreatic lipase activity in serum by a kinetic colorimetric
      assay using a new chromogenic substrate.
AB  - We evaluate a new assay reagent for lipase determination, based on the use of 1,2
      o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) as
      substrate. DGGR is cleaved by lipase, resulting in an unstable dicarbonic acid
      ester which is spontaneously hydrolysed to yield glutaric acid and
      methylresorufin, a bluish-purple chromophore with peak absorption at 580 nm. The
      rate of methylresorufin formation is directly proportional to the lipase activity
      in the sample. Bile salts, colipase and calcium chloride are included to provide
      optimal reactivity and specificity. Analysis of total imprecision gave a
      coefficient of variation of between 5.7% and 9.6%. Anticoagulants, common
      interfering substances and carboxylesterase had no effect on the assay, but
      interference by increased concentrations of serum triglycerides was noted. Good
      correlations were obtained with turbidimetry and a coupled enzymatic method. The
      estimated reference interval was 6-38 U/L. The unique characteristics of the
      chromogenic substrate qualify the present method as an innovative approach to
      serum lipase analysis.

PMID- 11471879
TI  - Interference in spectrophotometric analysis of cerebrospinal fluid by haemolysis
      induced by transport through a pneumatic tube system.
AB  - The hypothesis that sending blood-stained cerebrospinal fluid (CSF) through a
      pneumatic tube causes in vitro haemolysis has been tested. Spectrophotometric
      scanning of CSF supernatants demonstrated a significantly greater absorbance at
      415 nm in those CSF samples that had been sent through the tube system compared
      to those that had not (P=0.0034). It is concluded that passage of blood-stained
      CSF down a pneumatic tube system causes in vitro haemolysis, accompanied by the
      release of oxyhaemoglobin from the lysed cells into the surrounding CSF. In view
      of this observation, it is recommended that CSF samples requiring
      spectrophotometric analysis, as part of the investigation of subarachnoid
      haemorrhage, should not be transported via a pneumatic tube system.

PMID- 11471880
TI  - Drug interference in clinical chemistry: recommendation of drugs and their
      concentrations to be used in drug interference studies.
AB  - A group of international experts prepared two lists of drugs with their
      serum/plasma and urine concentrations, which should be used when evaluating the
      performance of a new laboratory method. The two lists were verified by running in
      vitro interference studies in three European laboratories on Hitachi instruments.
      The study identified the following new interferants: acid phosphatase in serum by
      ibuprofen and theophylline; non-prostatic acid phosphatase in serum by cefoxitin
      and doxycycline; creatine kinase MB in serum by doxycycline; total bilirubin in
      serum (Jendrassik-Grof method) by rifampicin and intralipid; total bilirubin in
      serum (DPD method) by intralipid; creatinine in serum (Jaffe method) by
      cefoxitin; fructosamine in serum by levodopa and methyldopa; uric acid in serum
      by levodopa, methyldopa and tetracycline; carbamazepine in serum by doxycycline,
      levodopa, methyldopa and metronidazole; digitoxin in serum by rifampicin;
      phenytoin in serum by doxycycline, ibuprofen, metronidazole and theophylline;
      theophylline in serum by acetaminophen, cefoxitin, doxycycline, levodopa,
      phenylbutazone and rifampicin; tobramycin in serum by cefoxitin, doxycycline,
      levodopa, rifampicin and phenylbutazone; valproic acid in serum by
      phenylbutazone; C3 in serum by intralipid; C4 in serum by doxycycline; rheumatoid
      factor in serum by ibuprofen and metronidazole; pancreatic amylase and total
      amylase in urine by acetylcysteine, ascorbic acid, cefoxitin, gentamicin,
      levodopa, methyldopa and ofloxacin; magnesium in urine by acetylcysteine,
      gentamicin and methyldopa; beta2-microglobulin in urine by ascorbic acid; total
      protein in urine by ascorbic acid, Ca-dobesilate and phenylbutazone. Interference
      in acid phosphatase, creatine kinase MB and bilirubin methods was observed at
      very low analyte concentrations, and therefore it may not be evident at higher
      concentrations. The study confirmed the usefulness of the recommendation.

PMID- 11471881
TI  - Pseudohyperkalaemia caused by recentrifugation of blood samples after storage in
      gel separator tubes.
AB  - Because hyperkalaemia above a certain level is life-threatening, erroneous
      interpretation of serum potassium concentration may misguide and complicate
      diagnostic procedures. We investigated a number of cases with
      pseudohyperkalaemia, which was assumed to have been caused by the
      recentrifugation of blood samples after storage in gel separator tubes. The time
      trend of serum potassium concentration was explored before (January-March 1997)
      and after (May-July 1997) ceasing the practice of recentrifuging blood samples
      after overnight storage. Next, we conducted an experiment on a volunteer's serum.
      The sample was divided into two groups and centrifuged once (control group) or
      twice (recentrifugation group). For both groups, serum potassium concentrations
      were measured immediately, and at 24, 48 and 72 h. For the recentrifugation
      group, the second centrifugation was done just before the measurement. The time
      series study showed that the mean serum potassium concentrations measured after
      overnight storage were 4.68 (95% CI: 4.60-4.76) mmol/L before and 4.14 (4.07
      4.20) mmol/L after ceasing the practice of recentrifugation. The experiment
      showed that the mean serum potassium concentrations in the control group versus
      the recentrifugation group were 3.95 (95% CI: 3.89-4.01) mmol/L versus 4.05 (3.92
      4.17) immediately (P=0.0979), 3.95 (3.89-4.01) versus 5.95 (5.61-6.29) at 24 h
      (P=0.0001), 4.13 (4.05-4.22) versus 6.90 (6.46-7.34) at 48 h (P=0.0001), and 4.22
      (3.85-4.58) versus 7.61 (6.94-8.30) at 72 h (P<0.0001). Recentrifugation of blood
      samples after storage causes a spurious rise in serum potassium concentration to
      the degree of clinical significance. Clinicians and biochemists should take
      appropriate measures to stop this practice.

PMID- 11471882
TI  - Effects of renal sorbitol accumulation on urinary excretion of enzymes in
      hyperglycaemic rats.
AB  - We studied the effects of epalrestat, a specific inhibitor of aldose reductase,
      on renal sorbitol accumulation and the resulting urinary enzyme excretion in
      hyperglycaemic rats. The activities of proximal tubule-derived enzymes such as N
      acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), gamma
      glutamyltranspeptidase (GGT) and dipeptidyl aminopeptidase IV (DAPIV) in urine
      were determined in five groups of male Wistar rats (each n = 7): (a) 0.9% saline
      loaded, (b) 10% glucose-loaded, (c) 10% glucose-loaded with epalrestat
      pretreatment, (d) 10% mannitol-loaded and (e) 10% mannitol-loaded with epalrestat
      pretreatment. Epalrestat was given mixed in chow at a dose of 50 mg/kg body
      weight. Urinary NAG, AAP, GGT and DAPIV activities were significantly increased
      (P<0.005, P<0.05, P<0.01, P<0.01, respectively) by the induction of
      hyperglycaemia. In contrast, enzyme excretion was not increased in the mannitol-
      or saline-loaded groups. Pre-treatment with epalrestat completely prevented the
      increased urinary excretion of NAG, AAP and GGT. At the end of the infusion
      study, renal cortical glucose concentrations of the glucose-loaded groups with
      and without epalrestat pretreatment were approximately fivefold higher than those
      of the mannitol- or saline-loaded groups (P<0.005 each). Renal cortical sorbitol
      concentrations of the glucose-loaded group was also approximately twofold higher
      than those of the mannitol- or saline-loaded groups (P<0.01 each). However, in
      the group that received both glucose and epalrestat, renal cortical sorbitol
      concentration was not increased. These results suggest that accumulation of
      intracellular sorbitol leads to proximal tubular cell dysfunction and abnormal
      enzymuria.

PMID- 11471883
TI  - Association between apolipoprotein B promotor haplotypes and cholesterol status.
AB  - Association between apolipoprotein B (apo B) promoter haplotypes and cholesterol
      concentration was studied in two groups of children with low and high
      concentrations of cholesterol. Strong linkage equilibrium was demonstrated
      between I/D in the signal peptide of apo B and (C-516T) polymorphism in the
      promotor of apo B gene, and the I/I+ allele T haplotype was associated with a low
      cholesterol concentration.

PMID- 11471884
TI  - Oxidative stress in haemodialysis: immediate changes caused by passage of blood
      through the dialyser.
AB  - Oxygen free radicals have been implicated in the long-term complications of
      maintenance haemodialysis. Studies that have probed into the mechanisms of oxygen
      radical production have implicated the bio-incompatibility of dialysis membranes.
      Changes between the arterial (inlet) and venous (outlet) points of a dialyser may
      give a better picture of blood membrane interaction. There are very few studies
      on changes across the dialyser. Hence, it was planned to study the immediate
      changes that occur due to passage of blood through the dialyser. Changes between
      the arterial and venous ends of the dialyser after 1 h of dialysis were studied
      in four combinations of dialysate and membrane. There was a significant decrease
      in plasma vitamin E concentrations in all the groups during first-use dialysis.
      This was not observed with re-use dialysis. A decrease in plasma lipid peroxides
      was also observed in all the groups with both first and re-use dialysis. There
      was no significant difference in the parameters studied among the four types of
      dialysis. A less severe, reactive oxygen radical generation was observed with re
      use of membranes.

PMID- 11471885
TI  - A falling HbA1c is not necessarily an indicator of improving diabetes control.
AB  - The finding of a very low haemoglobin A1c (HbA1c) (1.4%) in a diabetic patient
      with fairly high plasma glucose levels prompted haematological investigations,
      which revealed auto-immune haemolysis and a Hb concentration of 7.7 g/L.
      Following treatment, both Hb and HbA1c concentrations increased roughly in
      parallel until, 4 months later, Hb was 13.8 g/L, HbA1c 5.2% and plasma glucose
      was 6.8 mmol/L. This case illustrates that a falling HbA1c cannot always be
      attributed to improving glucose control in diabetic patients.

PMID- 11471886
TI  - Herbal remedy poisoning presenting with acute abdomen and raised urine
      porphyrins.
AB  - We describe a case of lead poisoning due to herbal remedies, presenting with an
      acute abdomen, raised porphyrins and increased liver enzyme activities. We
      suggest that lead poisoning should be considered in the differential diagnosis of
      the 'acute abdomen', and that the presence of liver dysfunction points to the
      possibility of Asian herbal remedies as the source of the lead poisoning.

PMID- 11471887
TI  - NHS laboratories can provide a service to the pharmaceutical industry: a personal
      experience.

PMID- 11471888
TI  - Gender differences in urinary excretion rates of cortisol and androgen
      metabolites.

PMID- 11471889
TI  - Evaluation of effect of analytical imprecision in maternal serum screening for
      Down's syndrome.

PMID- 11471890
TI  - Solid-phase extraction as an alternative to dichloromethane in analysis of urine
      free cortisol.

PMID- 11471891
TI  - Lactulose-mannitol intestinal permeability test: a useful screening test for
      adult coeliac disease.

PMID- 11471892
TI  - Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology
      proven hepatocellular carcinoma.
AB  - INTRODUCTION: Serum alpha-fetoprotein (AFP) is a useful marker of hepatocellular
      carcinoma (HCC), although the serum AFP concentration is also increased in
      patients with chronic liver diseases (CLD). The analysis of AFP glycoforms has
      been known to be of diagnostic value. We applied the lectin-affinity
      electrophoresis and antibody-affinity blotting techniques to HCC patients in
      Vietnam in order to better understand the role of lentil lectin-affinity AFP-L3
      in the diagnosis and differential diagnosis of HCC, and its relationship with the
      biological characteristics of HCC. METHODS: Lens culinaris agglutinin-reactive
      AFP (AFP-L3) was measured in 65 patients with histologically proven HCC and 25
      patients with CLD. All patients had serum AFP levels above 54 ng/mL. AFP-L3
      levels were determined by lectin affinity electrophoresis coupled with antibody
      affinity blotting. The diagnosis of HCC was confirmed histologically by
      ultrasound-guided biopsy. RESULTS: The mean value of AFP-L3 in the HCC patients
      was 49.6 +/- 21.6%, which was significantly higher (p<0.001) than that in the 25
      CLD patients (10.7 +/- 4.3%). When the cutoff level for AFP-L3 was set at 15%
      (mean +/- SD), the sensitivity was 96.9%, the specificity 92.0% and the accuracy
      95.5% in the 65 HCC patients. There was no clear correlation between serum AFP
      level and AFP-L3 percentage (r=0.16). There was no correlation between AFP-L3 and
      the maximum diameter of HCC nodules (r=0.05). However, the mean AFP-L3 value was
      higher in moderately or poorly differentiated HCC than in well differentiated
      tumors (p<0.001). CONCLUSIONS: AFP-L3 is potentially a clinically useful marker
      for the differentiation of increased AFP levels in hepatocellular carcinoma and
      chronic liver diseases. The AFP-L3 percentage is closely related to HCC
      differentiation. We consider the analysis of AFP-L3 a useful adjunct in the
      diagnosis of HCC.

PMID- 11471893
TI  - Detection of circulating mammary mucin (Muc1) and MUC1 immune complexes (Muc1
      CIC) in healthy women.
AB  - There is convincing epidemiological evidence that multiparity provides protection
      against the development of breast cancer. In the present study we evaluated the
      levels of MUC1 and MUC1 circulating immune complexes (MUC1-CIC) in 135 serum
      samples obtained from healthy women. The study population included 13 women who
      had never been pregnant, 31 primiparous pregnant women, 36 multiparous pregnant
      women who had lactated, 5 multiparous pregnant women who had never lactated, 24
      multiparous non-pregnant women who were lactating at the time of the study, 24
      multiparous non-pregnant women who had lactated, and 2 multiparous non-pregnant
      women who had never lactated. The purpose of this work was to detect MUC1
      variations during pregnancy and lactation as well as to study the possible
      induction of a humoral immune response against MUC1 in these conditions. We
      employed ELISA techniques to measure MUC1 (CASA test) and MUC1-CIC (IgM and IgG)
      using two anti-MUC1 monoclonal antibodies (MAbs): C595 and SM3. Statistical
      analysis was performed using the ANOVA test. The pooled results pertaining to
      pregnant versus non-pregnant women were compared and significant differences were
      observed in MUC1 and MUC1-CIC-lgM levels detected with both MAbs; the MUC1-CIC
      lgG levels detected with C595 were increased in the pregnant group while the MUC1
      CIC-lgG levels detected with SM3 did not show any significant differences. When
      the results were compared between lactating and non-lactating women, no
      significant differences were found. In conclusion, MUC1 and MUC1-CIC-lgM,
      detected with both MAbs, and MUC1-CIC-4gG levels detected with the MAb C595 are
      apparently induced by pregnancy.

PMID- 11471894
TI  - Prognostic value of the glycoprotein TAG-72 in patients with gastric cancer.
AB  - The specificity of the tumor markers used to date in patients with gastric cancer
      has not been satisfactory. For this reason we decided to evaluate the utility of
      TAG-72 in this disease. Between 1993 and 1998 we determined the levels of TAG-72
      in 638 subjects (148 healthy volunteers, 33 patients with chronic renal failure
      (CRF), 149 patients with benign diseases of the liver, 95 patients with benign
      gastrointestinal diseases and 213 patients with gastric cancer). TAG-72 was
      measured using an IRMA method. Statistical analysis of the data was performed
      with the BMDP package. We established a cutoff for TAG-72 of 3 U/mL,
      corresponding to the 92.6th percentile of the healthy controls. We observed that
      neither CRF nor benign liver diseases affected TAG-72 levels, while certain
      benign gastrointestinal diseases did cause alterations of the marker. Using Cox
      multivariate analysis we discovered that the preoperative TAG-72 level was an
      independent prognostic variable associated with both disease-free and overall
      survival. We conclude that, although TAG-72 is not useful for the diagnosis of
      gastric cancer, it is a suitable tool for disease monitoring and prognostic
      assessment.

PMID- 11471895
TI  - Serum levels of interleukin-18 and sICAM-1 in patients affected by breast cancer:
      preliminary considerations.
AB  - Interleukin-18 (IL-18), a cytokine that plays an important role in the T-cell
      helper type 1 response, acts as an angiogenesis and tumor suppressor.
      Intercellular adhesion molecule-1 (ICAM-1) has a potential role in
      immunoregulation by mediating immune cell infiltration into the tissue. The aim
      of this study was to evaluate IL-18 and soluble (s) ICAM-1 serum levels in breast
      cancer (BCa) patients with liver (BCaM1 h) or bone (BCaM1 b) metastases compared
      to BCa patients without metastases (BCaM0) and healthy donors (HDs). Furthermore,
      since IL-18 enhances ICAM-1 expression, we investigated whether there was a
      direct correlation between sICAM-1 and IL-18 serum levels. Serum IL-18 and sICAM
      1 levels were assayed by immunoenzymatic methods. The serum sICAM-1 levels in the
      three groups of cancer patients were significantly higher (p<0.05) than those of
      HDs. Serum IL-18 levels were significantly higher (p<0.05) in BCaM1h and BCaM1b
      patients compared to BCaM0 patients and HDs. sICAM-1 proved to be closely
      correlated with serum IL-18 levels in HDs, whereas a weaker correlation was found
      in BCaM1h, BCaM1b and BCaM0 patients. The defective correlation between sICAM-1
      and IL-18 found in cancer patients may contribute to our understanding of the
      immunity upset occurring in cancer. Our data suggest that IL-18, irrespective of
      its biological activity, could represent a marker for metastatic breast cancer.

PMID- 11471896
TI  - Cytokeratins as serum markers in egyptian bladder cancer. A comparison of CYFRA
      21-1, TPA and TPS.
AB  - Cytokeratins (CKs) have been shown to be overexpressed in bladder cancer and to
      be valuable as tumor markers. The present study was designed to evaluate the
      single and combined use of three cytokeratin fragments, CYFRA 21-1, TPA, and TPS,
      in serum of Egyptian bladder cancer patients. The study subjects comprised 40
      healthy controls, 30 patients with benign bladder diseases, and 60 patients with
      histologically confirmed primary bladder cancer. The cutoff was set at 95%
      specificity versus benign bladder diseases, resulting in cutoff values of 2.93
      ng/mL for CYFRA 21-1, 158 U/L for TPA and 143.7 ng/mL for TPS. With 41% true
      positive results CYFRA 21-1 had a higher sensitivity than TPA (32%) and TPS
      (27%). Evaluation by histological findings revealed a highest sensitivity of
      CYFRA 21-1 (46%) in transitional cell carcinoma (TCC) followed by TPA (27%) and
      TPS (21%). Also in adenocarcinoma CYFRA 21-1 showed the highest sensitivity (38%)
      followed by TPA (32%) and TPS (28%). A high percentage (41.6%) of Egyptian
      bladder cancers is represented by squamous cell carcinoma (SCC). In this
      population TPS showed the highest sensitivity (69%), followed by CYFRA 21-1 (54%)
      and TPA (41 %). The sensitivity of each of the three markers increased with
      advancing tumor stage and increasing tumor grade. Combined use of two of the
      three markers did not raise the sensitivities obtained by single determination of
      CYFRA 21-1. The present study suggests that serum CYFRA 21-1 could be a marker of
      choice in bladder cancer.

PMID- 11471897
TI  - Biomarkers and imaging in non-malignant and malignant osteomalacia.
AB  - Deoxypyridinium (DPD) cross-links are a specific parameter for collagen type I
      degradation. We report the longitudinal tracking of DPD in relation to other bone
      markers and imaging techniques in a patient with osteomalacia and secondary
      hyperparathyroidism from reduced light exposure due to attire. This patient was
      first admitted for diffuse skeletal pain. X-rays showed general demineralization
      and Looser's transformation zones in the neck of the left femur. MRI examinations
      of the pelvis and the proximal femora demonstrated bilateral signs of acute
      sacroiliitis, as well as edema-like lesions in the femoral heads and necks
      bilaterally. The baseline parathyroid hormone level was 8 times higher than the
      normal upper limit, whereas 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
      levels were significantly reduced. A 7-fold increase in free urinary DPD and a 17
      fold increase in bone-specific alkaline phosphatase (bone-AP) were also measured.
      Percutaneous transiliac bone biopsy revealed markedly increased osteoidosis.
      Osteomalacia was diagnosed due to chronically reduced sun exposure caused by
      restrictive attire, and cholecalciferol substitution therapy was begun. After a
      follow-up of 28 weeks, non-specific parameters of bone turnover (parathyroid
      hormone, total alkaline phosphatase, serum calcium and serum phosphate) had
      normalized, while DPD, as a specific bone degradation marker, and bone-AP, as a
      bone formation parameter, both remained elevated. This example underlines the
      validity of DPD and bone-AP as indicators of increased bone metabolism: not only
      were they the parameters with the highest baseline deviation, but they were also
      the last to normalize.

PMID- 11471898
TI  - Pepsinogen C: a possible biological marker of epithelial differentiation in
      Barrett's esophagus.

PMID- 11471899
TI  - Stimulation of IL-18 secretion by IL-2 in patients with advanced cancer.

PMID- 11471900
TI  - Serum tumor markers: past, state of the art, and future.
AB  - Serum determinations of tumor markers are indispensable in the diagnosis and
      management of cancer, and therefore play an important role in clinical practice.
      After a short historical survey, we systematically review a number of
      contemporary aspects of serum tumor markers related to various organ systems, and
      briefly indicate possible future developments.

PMID- 11471901
TI  - Validation of blood collection procedures for the determination of circulating
      vascular endothelial growth factor (VEGF) in different blood compartments.
AB  - AIMS OF THE STUDY: Studies on circulating VEGF have reported mixed results,
      possibly due to a lack of standardization of the pre-analytical phase. The aim of
      our investigation was to standardize the sampling procedure for the determination
      of VEGF in different blood fractions. BASIC PROCEDURES: We evaluated various
      clotting times for obtaining serum in 30 subjects, as well as different
      procedures for the preparation of plasma Edinburgh anticoagulant mixture (EDTA,
      PGE1, theophylline) and CTAD. VEGF was also assayed in lysed whole blood. In
      vitro platelet activation was monitored by measuring the levels of PF4. VEGF and
      PF4 were measured using commercially available enzyme-linked immunoassays. MAIN
      FINDINGS: Clotting time increased the release of VEGF, which reached a plateau
      between 2 and 4 hours. The percent increase of VEGF at 2 hours ranged from 118%
      to 4,515% (median 327%) compared to samples centrifuged within 10 min from
      withdrawal. VEGF was not different and PF4 was very low or undetectable in
      Edinburgh plasma and CTAD plasma, while it was significantly higher in sodium
      citrate plasma. VEGF in CTAD plasma was not correlated with platelet count or
      leukocytes. Serum VEGF did not correlate with the leukocyte number, but it
      correlated significantly with the platelet count. PRINCIPAL CONCLUSIONS: The
      procedures for sample collection described above are highly standardized and easy
      to perform in a routine setting. We therefore suggest systematic evaluation of
      VEGF in CTAD plasma, in serum (clotting for 2 hours at room temperature) and in
      whole blood, until prospective controlled clinical studies will have clarified in
      which blood compartment(s) VEGF provides clinically relevant information.

PMID- 11471902
TI  - Prognostic significance of DNA aneuploidy and p21 ras oncoprotein expression in
      colorectal cancer and their role in the determination of treatment modalities.
AB  - The purpose of the present study was to investigate the prognostic significance
      of DNA ploidy, S-phase fraction and p21 ras oncoprotein expression in patients
      with colorectal cancer and to correlate these factors with the clinical behavior
      of the tumors and their response to therapy. Of 79 patients with colorectal
      cancer 57% (45/79) had early stage disease. Forty-one percent (32/79) had
      aneuploid tumors while 30% (24/79) of the tumors had a high (>10%) S-phase
      fraction. p21ras oncoprotein expression was detected in 38% (30/79) of tumors.
      Patients with aneuploid tumors had a worse prognosis than patients with diploid
      tumors (p=0.0002). Similarly, patients with high S-phase fraction tumors had a
      shorter survival than those with low S-phase fraction tumors (p=0.005). No such
      difference was found between p21 raspositive and p21 ras-negative tumor
      subgroups. In early stage colorectal cancer, aneuploidy was closely correlated
      with disease outcome (p=0.029). Early stage patients with diploid tumors who
      received radiotherapy and chemotherapy had a better prognosis than patients with
      aneuploid tumors. In conclusion, DNA ploidy is a significant and independent
      prognostic factor in colorectal cancer. Aneuploidy and genetic alteration of the
      p21 ras oncoprotein are important in determining the biological aggressiveness of
      colorectal cancer. Furthermore, DNA ploidy may identify those subgroups of
      patients with early stage disease who may benefit from more aggressive treatment.

PMID- 11471903
TI  - The performance of standard vertical S-1 flight maneuvers by student U.S. Naval
      helicopter pilots.
AB  - BACKGROUND: During flight training, student U.S. Naval helicopter pilots learn
      the use of flight instruments through a prescribed series of simulator training
      events. We recorded the training flights of 76 student U.S. Naval helicopter
      pilots undergoing the simulator phase of basic flight instrument training. From
      the final basic instrument simulator flight, the Vertical S-I (VS) flight
      maneuver, a standard flight maneuver required of the students, was selected for
      analysis. This maneuver was chosen because the ideal performance was well
      described. METHODS: The training simulator is the 2B42 training device, a 6
      degrees of freedom, motion-based, high-fidelity instrument trainer. The quality
      of the flight performance of the cohort of student aviators executing the VS was
      described using objective measures of deviation from the ideal flight path. The
      measures included air speed, altitude, and heading average error from target
      values and standard deviations. RESULTS: The distributions of these scores for
      the 76 student pilots were described and used to calculate a composite score that
      summarized a student's overall performance of the maneuver. The worst four, the
      best four, and a group of four average pilots were identified from their
      composite scores and their relative performance was compared. CONCLUSIONS: A
      graphical summary of each pilot's flight performance was developed, and from this
      performance summary a pattern became evident that suggested that differences in
      performance levels were related to the use of flight instruments.

PMID- 11471904
TI  - The effect of aircraft control forces on pilot performance during instrument
      landings in a flight simulator.
AB  - BACKGROUND: Pilots may have difficulty controlling aircraft at both high and low
      force levels due to larger variability in force production at these force levels.
      The aim of this study was to measure the force variability and landing
      performance of pilots during an instrument landing in a flight simulator.
      METHODS: There were 12 pilots who were tested while performing 5 instrument
      landings in a flight simulator, each of which required different control force
      inputs. Pilots can produce the least force when pushing the control column to the
      right, therefore the force levels for the landings were set relative to each
      pilot's maximum aileron-right force. The force levels for the landings were 90%,
      60%, and 30% of maximal aileron-right force, normal force, and 25% of normal
      force. Variables recorded included electromyographic activity (EMG), aircraft
      control forces, aircraft attitude, perceived exertion and deviation from glide
      slope and heading. Multivariate analysis of variance was used to test for
      differences between landings. RESULTS: Pilots were least accurate in landing
      performance during the landing at 90% of maximal force (p < 0.05). There was also
      a trend toward decreased landing performance during the landing at 25% of normal
      force. Pilots were more variable in force production during the landings at 60%
      and 90% of maximal force (p < 0.05). CONCLUSION: Pilots are less accurate at
      performing instrument landings when control forces are high due to the increased
      variability of force production. The increase in variability at high force levels
      is most likely associated with motor unit recruitment, rather than rate coding.
      Aircraft designers need to consider the reduction in pilot performance at high
      force levels, as well as pilot strength limits when specifying new standards.

PMID- 11471905
TI  - The relative impact of generic head-related transfer functions on auditory speech
      thresholds: implications for the design of three-dimensional audio displays.
AB  - BACKGROUND: Auditory speech thresholds were measured in this study. METHODS:
      Subjects were required to discriminate a female voice recording of three-digit
      numbers in the presence of diotic speech babble. The voice stimulus was
      spatialized at 11 static azimuth positions on the horizontal plane using three
      different head-related transfer functions (HRTFs) measured on individuals who did
      not participate in this study. The diotic presentation of the voice stimulus
      served as the control condition. RESULTS: The results showed that two of the
      HRTFS performed similarly and had significantly lower auditory speech thresholds
      than the third HRTF. All three HRTFs yielded significantly lower auditory speech
      thresholds compared with the diotic presentation of the voice stimulus, with the
      largest difference at 60 degrees azimuth. CONCLUSION: The practical implications
      of these results suggest that lower headphone levels of the communication system
      in military aircraft can be achieved without sacrificing intelligibility, thereby
      lessening the risk of hearing loss.

PMID- 11471906
TI  - The influence of ethnicity on thermosensitivity during cold water immersion.
AB  - PURPOSE: This investigation evaluated the influence of ethnicity, Caucasian (CAU)
      vs. African American (AA), on thermosensitivity and metabolic heat production
      (HP) during cold water immersion (20 degrees C) in 15 CAU (22.7 +/- 2.7 yr) vs. 7
      AA (21.7 +/- 2.7 yr) males. METHODS: Following a 20-min baseline period (BASE),
      subjects were immersed in 20 degrees C water until esophageal temperature (Tes)
      reached 36.5 degrees C or for a maximum pre-occlusion (Pre-OCC) time of 40 min.
      Arm and thigh cuffs were then inflated to 180 and 220 mm Hg, respectively, for 10
      min (OCC). Following release of the inflated cuffs (Post-OCC), the slope of the
      relationship between the decrease in Tes and the increase in HP was used to
      define thermosensitivity (beta). RESULTS: ANOVA revealed no significant
      difference in thermosensitivity between CAU and AA (CAU = 3.56 +/- 1.54 vs. AA =
      2.43 +/- 1.58 W.kg(-1). degrees C(-1)). No significant differences (p > 0.05)
      were found for Tsk (CAU = 24.2 +/- 1.1 vs. AA = 25.1 +/- 1.1 degrees C) or HP (p
      > 0.05; CAU = 2.5 +/- 0.8 vs. AA = 36.5 +/- 1.8 W.kg(-1)). However, a significant
      (p < 0.05) main effect for ethnicity for Tes was observed (CAU = 36.7 +/- 1.8 vs.
      AA = 36.5 +/- 1.8 degrees C). CONCLUSION: These data suggest, despite a
      differential response in Tes between AA and CAU groups, the beta of HP during
      cold water immersion is similar between CAU and AA. Therefore, these data
      demonstrate that when faced with a cold challenge, there is a similar response in
      HP between CAU and AA that is accompanied by a differential response in Tes.

PMID- 11471907
TI  - Effectiveness and tolerability of melatonin and zolpidem for the alleviation of
      jet lag.
AB  - BACKGROUND: The aim of this study was to compare the effectiveness and
      tolerability of a chronobiotic (melatonin) with a hypnotic (zolpidem) and the
      combination of both substances to alleviate jet lag symptoms associated with
      eastward travel. METHODS: This double-blind, randomized, placebo-controlled study
      is based on 137 volunteers flying from Switzerland to the American continent and
      back (6-9 time zones). The participants either received melatonin 5 mg (n = 35),
      zolpidem 10 mg (n = 34), a combination thereof (n = 29) or placebo (n = 39) on
      the eastbound flight back to Switzerland and once daily at bedtime on 4
      consecutive days after the flight. The test battery included daily sleep logs,
      symptoms questionnaires, and the Profile of Mood States (POMS). Also, on the last
      treatment day, Visual Analog Scales (VAS) were completed to assess overall jet
      lag ratings and treatment effectiveness. Baseline data were collected on 4
      consecutive days 2 wk after the flight. During post-flight treatment and
      baseline, motor activity was assessed in a subgroup of 49 subjects using wrist
      worn ambulatory monitors. RESULTS: The self-rated sleep quality was significantly
      improved by zolpidem, especially during the night flight. Subjects taking
      zolpidem reported significantly less jet lag and zolpidem was rated as the most
      effective jet lag medication. However, zolpidem and the combination
      melatonin/zolpidem were less well tolerated than melatonin alone; adverse event
      reports included nausea, vomiting, amnesia and somnambulia to the point of
      incapacitation. Confusion, morning sleepiness and nausea were highest in the
      combination group. CONCLUSIONS: All active treatments led to a decrease of jet
      lag severity with zolpidem being the most effective treatment, particularly in
      facilitating sleep on night flights. Potential individual adverse reactions to
      this hypnotic have to be considered.

PMID- 11471908
TI  - Urinalysis drug testing within a civilian pilot training program: did attitudes
      change during the 1990's?
AB  - BACKGROUND: Attitudes toward fairness and effectiveness of mandatory drug testing
      vary within pilot populations (4,8) as well as other populations (3). This
      descriptive-correlational study examined civilian student pilots' attitudes
      toward urinalysis (UA) drug testing over a 10-yr period and the pilots' opinions
      regarding effectiveness, adequacy, and fairness of the testing as a deterrent for
      substance abuse among pilots. METHODS: A sample of three different groups of
      civilian aviation students (n = 314), consisted of 103 pilots studied prior to
      implementing a mandatory drug testing program, 113 pilots studied 1 yr after
      implementing a mandatory drug testing program, and 98 pilots studied 6 yr into a
      mandatory drug testing program. A 14-item questionnaire (alpha = 0.74),
      indicating degrees of agreement, was completed by the student pilots who were
      enrolled in a large civilian pilot training program. RESULTS: There were no
      significant differences among the study pilots' feelings related to anxiety of
      drug testing when comparing non-mandatory and mandatory groups over time. The
      pilots continue to believe that alcohol use by pilots within this civilian
      piloting training program has decreased since testing was mandated and that drug
      use also showed a significant decrease (p = 0.01), although not as significant (p
      = 0.0001) as the decrease in alcohol use. CONCLUSION: The study showed that
      alcohol and drug testing is more generally accepted by the pilots in the study as
      the decade of the 1990s came to a close.

PMID- 11471909
TI  - Using diplopia as a warning of an inappropriate visual (ocular) accommodative
      response (WIVAR).
AB  - BACKGROUND: Over-accommodation, a tendency to focus at a distance closer than the
      desired distance, has been previously shown to occur when using a head-up display
      (HUD). METHODS: A simple system was developed as a warning of an inappropriate
      visual accommodative response (WIVAR) during flight training. Two lines, which
      are seen as four low-contrast lines (physiological diplopia) if the user is
      focused in the distance due to the link between convergence and accommodation,
      are projected onto the pilot's HUD combiner. RESULTS: The results show that by
      using the WIVAR system the accommodative response can be kept more distant when
      viewing forward-looking infra-red imagery (by 0.12 +/- 0.04 D; p < 0.05),
      performing a high cognitive workload task (by 0.07 +/- 0.03 D; p < 0.05) and
      especially when viewing in a Ganzfeld (by 0.41 +/- 0.12 D; p < 0.01). CONCLUSION:
      While collimated HUD imagery stimulates the user to a more distant focus, the use
      of the WIVAR lines can cause additional relaxation of accommodation.

PMID- 11471910
TI  - U.S. Army MEDEVAC in the new millennium: a medical perspective.
AB  - The U.S. Army Aeromedical Evacuation community (MEDEVAC) possesses a long
      standing tradition of excellence in the care and transportation of combat
      casualties. Recent developments in civilian air medical transport and
      quantitative review of MEDEVAC operations have identified potential areas for
      improvement, concentrating on enhanced flight medic standards, training,
      sustainment and medical oversight of the air ambulance system. These proposed
      changes are discussed in detail, from the perspective of current emergency
      medicine and aviation medicine standards of practice. If instituted, these
      changes would facilitate the emergence of a true air medical transport capability
      comparable with the civilian community standard.

PMID- 11471911
TI  - Survival with pain: an eight-year follow-up of war-wounded refugees.
AB  - The aim of this study was to investigate the nature of chronic pain in male war
      wounded refugees and to examine the relationship between chronic pain and
      psychiatric symptoms. A culturally heterogeneous group of 44 war-wounded refugees
      were investigated during hospitalization, shortly after arrival, and followed up
      after two years. This study is an additional follow-up after eight years. The
      data collection methods used were structured interviews and physical examination.
      The measures of outcome were: Visual Analogue Scale (VAS) grading of pain;
      clinical categorization of pain into nociceptive or neurogenic; Hopkins Symptom
      Check List (HSCL-25); Post Traumatic Symptom Scale (PTSS-10). Chronic pain was
      found in 32 (73%) out of 44 subjects. The pain was purely nociceptive and
      neurogenic in 53% and 25%, respectively. The frequency of psychiatric symptoms
      was significantly related to the mean intensity of pain. War-wounded refugees
      display psychiatric symptoms and chronic pain in a complex pattern. Further
      research is needed as a basis for pain rehabilitation programmes suitable for
      this group.

PMID- 11471912
TI  - Ideological commitment, experience of conflict and adjustment in Northern Irish
      adolescents.
AB  - This study aims to assess young people's overall experience of political
      conflict, as well as the extent of these experiences in relation to gender,
      religious affiliation and residential location (high or low conflict). Second,
      this study assesses the impact that young people's ideological commitment and
      experiences of the conflict have on their self-esteem and mental health. A sample
      of 96 Protestant and Catholic young people (mean age 15.2), drawn from four
      schools in two areas of Northern Ireland, completed self-report measures of self
      esteem, mental health, ideological commitment and experience of conflict. The
      areas differed substantially in the amount of violence they had experienced. The
      results indicated that young people's experience of violence varied in relation
      to the town in which they lived. Boys' experience of violence appeared to be
      related to their religious affiliation. Experience of conflict and ideological
      commitment, two attributes that were positively related, interacted to predict
      both mental health and self-esteem. The importance of ideological commitment to
      our understanding of the impact of political conflict on young people is
      discussed.

PMID- 11471913
TI  - Providing health care for refugee children and unaccompanied minors.
AB  - The health of refugee children must be considered beyond ensuring access to
      health care to include issues such as housing and education. Refugees require
      support in using services, and their culture and religious background must be
      taken into account. Asylum seeking children have the same rights to health as any
      other children, yet non-eligibility for welfare foods may have implications for
      their nutrition. Providing for 15-18 year olds presents particular problems. It
      is important to arrange access to appropriate care for unfamiliar diseases and to
      recognize emotional health problems, particularly when they are related to past
      experiences of violence.

PMID- 11471914
TI  - How primary care services can incorporate refugee health care.
AB  - Two principles should underpin the provision of primary health care to refugees:
      (a) that refugees should have the same access to quality primary care services as
      the local population, and (b) any specialist service should have the goal of full
      integration of the refugee into normal general practice. The various ways in
      which medical care can be provided to refugees and the knowledge, skills and
      attitudes important to such provision are described. One way in which such a
      service was provided in east Kent is reported. The term 'refugee' encompasses
      newly arrived refugees who are awaiting a decision from the Home Office, as well
      as those who have been given permission to stay, either as recognized Refugees
      under the provisions of the 1951 United Nations Convention, or with Exceptional
      or Indefinite Leave to Remain.

PMID- 11471915
TI  - Children of traumatized and exiled refugee families: resilience and
      vulnerability. A case study report.
AB  - This paper focuses on the main problems and outcomes of two children of a
      traumatized refugee family who have been in Britain since 1993. Their parents
      witnessed near death experiences and physical assaults, and suffered losses and a
      wide range of physical problems; the father manifests post traumatic stress
      disorder (PTSD) symptoms. The children have been exposed regularly to episodic
      rage and violent behaviour by their father, and have developed separation
      problems and psychosomatic complaints. Their mother has coped better and is very
      resilient in her care and approach to problems. This report acknowledges the
      negative experience of trauma, but also the sources of resilience of parents,
      children's adjustment and cultural differences in coping styles. Refugee
      experiences devastate individual well-being and coping mechanisms if there is no
      hope, support and faith in one's own potential. Protective and risk factors that
      may affect the manifestation of trauma symptoms are highlighted. A variety of
      treatment approaches are required for both adult and child victims of multiple
      trauma. A wide range of techniques, such as group therapy, behaviour and
      cognitive therapy, and desensitization and relaxation training, can help
      sufferers to enhance their coping skills and deal effectively with devastating
      life events.

PMID- 11471916
TI  - Reconciliation and healing of a nation.
AB  - This article explores the effect of mass trauma and how it is dealt with both
      individually and socially. The question why the systematic massacres happened in
      Cambodia is addressed. Also covered is a brief history of the continual divisions
      in Cambodian society. The Cambodians have not come to terms with their tragedy or
      moved closer to the rest of the world. Some means of reconciliation are
      suggested.

PMID- 11471917
TI  - Colloquium on 'a Culture of Peace'.

PMID- 11471919
TI  - Recent papers and news items.

PMID- 11471918
TI  - Non-governmental UN millennial events.

PMID- 11471920
TI  - The hidden casualties of conflict.

PMID- 11471921
TI  - Female reproductive endocrinology at the turn of the millennium.
AB  - The mainstays of female reproductive endocrinology, even as the millennium occurs
      and we cite highly technological advances in assisted reproduction, continue to
      be-as for the past decade-and-a-half-the use of GnRH analogs, both agonists and
      antagonists; the use of other gonadotropins, both alone and in combination, as
      well as with other types of drugs; testing for "ovarian reserve," as we attempt
      infertility treatment for populations that now include more nulliparous women of
      older reproductive age; and diagnosing and treating polycystic ovarian syndrome
      (PCOS), for both its reproductive and general health effects, especially as
      concerns insulin resistance. These topics are covered in detail, with reviews of
      well-controlled, and sometimes contrasting, studies.

PMID- 11471922
TI  - The diagnosis and treatment of male infertility in the new millennium.
AB  - Treatment of male infertility accomplished far-reaching advances in the past
      decade. Semen analysis has given rise to sperm function tests. Microsurgery,
      e.g., reversal of vasectomy, has reached new heights in sperm retrieval directly
      from the testis/epididymis and in intracytoplasmic sperm injection (ICSI).
      Furthermore, genetic testing-for an ever-widening range of anomalies-is the norm
      in modern clinical practice. This review of what is possible, and now even
      common, in male infertility treatment focuses on sperm function, and then
      deficits/anomalies and their treatment; and testicular function and dysfunction,
      with descriptions of hormonal and surgical techniques that now offer fatherhood
      to men with types of infertility that strongly imply the need for genetic
      counseling.

PMID- 11471923
TI  - IVF: the new era.
AB  - In-vitro fertilization (IVF) has made great strides in the past 25 years
      including the development of micromanipulation techniques. Intracytoplasmic sperm
      injection (ICSI) for treatment of severe male factor infertility paved the way
      for the use of the micromanipulator. Micromanipulation techniques are now an
      integral part of an IVF program and are now also employed to biopsy embryos from
      patients harboring genetic abnormalities. Micromanipulation has also been used in
      the development of nuclear transfer techniques--a potential solution for creating
      "younger" oocytes for women of advanced maternal age and spermatozoa for
      azoospermic men. Other recent developments include the sequential media enabling
      the embryo to survive to blastocyst stage and also successful oocyte
      vitrification to preserve future fertility. This paper describes the latest
      technologies in in-vitro fertilization and relates them to the total problem of
      infertility, age-related and otherwise.

PMID- 11471924
TI  - Laparoscopic Fertility-Promoting Procedures of the fallopian tube and the uterus.
AB  - Assisted reproductive technology and reproductive surgery can be complementary,
      and the feasibility of laparoscopic suturing has facilitated conducting
      reproductive surgery entirely by laparoscopy. Young women with tubal disease can
      be offered surgery, whereas older women, with their rapid decline in fertility,
      are better treated with in vitro fertilization (IVF). IVF should be the first
      line of treatment for women with a severe degree of hydrosalpinx, or with
      extensive and dense adhesions. However, the presence of hydrosalpinx decreases
      IVF pregnancy rates. In those whose hydrosalpinx is seen on ultrasound,
      especially after failed IVF cycles, a laparoscopic salpingectomy can be done. For
      tubal anastomosis, the superior results of this procedure are well established.
      The association between uterine myoma and infertility is unclear. However, in
      those with a distorted uterine cavity, and no other cause of infertility,
      myomectomy can be considered; myomectomy can be done by laparoscopy. Because of
      the risks of uterine rupture, proper closure of the uterine incision is of utmost
      importance.

PMID- 11471925
TI  - Endometriosis: traditional perspectives, current evidence and future
      possibilities.
AB  - Endometriosis is a disease that is wide-ranging in location and highly varied in
      clinical presentation, and of probably complex etiology. Since convincing studies
      on this condition are few, many physicians maintain a traditional perspective in
      management and treatment. There is new evidence, though, on some aspects of
      endometriosis. Therefore, this review of many of the better studies outlines
      treatments that are aimed at pain and/or infertility, plus an assessment of the
      outcomes obtained. The methods covered are symptomatic treatment; ovarian
      suppression; surgery; combined ovarian suppression and surgery; ovarian
      hyperstimulation; assisted reproductive technology; and comprehensive management,
      including counseling.

PMID- 11471926
TI  - The new genetic era in reproductive medicine: possibilities, probabilities and
      problems.
AB  - The "New Genetic Era" will be a period of enormous exponential growth in our
      knowledge of the structure and function of the basic information blocks of life.
      The Human Genome Project will soon provide a complete and accurate sequence of
      the human genome. This will give us an abundance of basic genetic knowledge and
      provide a molecular understanding of disease, allowing for improved diagnosis and
      more sensitive and specific screening for disease. This will, we hope, lead to
      better treatments, prevention and cures through gene therapy, patient-specific
      drug design, and earlier and more specific behavioral interventions to prevent
      disease. With this information comes a complexity of legal, ethical and social
      concerns about potential use and abuse. The public has expressed its concerns
      about the potential for genetic discrimination. However, genetic information is
      enhancing our knowledge as to the causes of infertility, allowing diagnosis of
      more diseases in the prenatal period, and may aid our identification of patients
      at increased risk for breast and ovarian cancer. Doctors involved in reproductive
      medicine must become knowledgeable about the new genetic era so as to offer our
      patients the most appropriate and informed care.

PMID- 11471927
TI  - The effect of atorvastatin on postprandial lipaemia in overweight or obese women
      homozygous for apo E3.
AB  - OBJECTIVE: To determine the effect of atorvastatin on postprandial lipaemia in
      overweight or obese women with the apoprotein (apo) E3/E3 genotype. DESIGN:
      Double-blind randomised, placebo-controlled 8-week single-centre study. SUBJECTS:
      Twenty-two healthy women, homozygous for apo E3 with a BMI ranging from 27.6 to
      41.1 kg/m2 and normal or moderately elevated fasting triglycerides (53-184
      mg/dl). TREATMENT: After a 4-week isocaloric single-blind, placebo lead-in
      period, subjects were randomly assigned to receive either placebo (n = 7) or
      atorvastatin 20 mg once daily in the evening (n = 15) for 4 weeks. RESULTS:
      Atorvastatin significantly reduces fasting total cholesterol, LDL-cholesterol and
      postprandial triglycerides in obese women, homozygous for apo E3 with normal or
      near-normal fasting triglyceride levels. No significant effect on fasting
      triglycerides was observed. CONCLUSION: Atorvastatin decreases postprandial
      hyperlipidaemia, an independent cardiovascular risk factor, in normolipidaemic
      obese women. This effect of atorvastatin may, therefore, represent a
      cardioprotective mechanism.

PMID- 11471928
TI  - Surgery of rheumatic mitral stenosis: comparison of different techniques.
AB  - OBJECTIVE: The breakthrough of percutaneous transvenous mitral commissurotomy
      (PTMC) has dramatically changed the indications for the surgical treatment of
      rheumatic mitral stenosis over the last decade. No recent studies comparing long
      term results of PTMC, open mitral commissurotomy (OMC) and mitral valve
      replacement (MVR) with bileaflet prostheses are available in medical literature.
      METHODS AND RESULTS: Between January 1991 and December 1997, 313 patients with
      pure and isolated rheumatic stenosis were treated in our department. One hundred
      and eleven patients underwent PTMC, 82 OMC and 120 MVR. There was no statistical
      difference (p>0.05) between the mortality rates of the three groups of patients.
      No cases of hospital mortality were observed in the patients who underwent PTMC
      and OMC, whereas two patients (1.6%) died within 30 days after MVR. Seven year
      actuarial survival results are: 95.41+/-2(SE)% (PTMC), 98.05+/-1% (OMC) and
      92.82+/-33% (MVR) (p=NS). Freedom from embolism was 98.78+/-1% in PTMC, 98.78+/
      1% in OMC and 92.52+/-2% in MVR (p>0.05); freedom from reoperation was 88.43+/-8%
      in PTMC, 96.35%+/-2% in OMC and 97.72+/-1% in MVR (p>0.05). The mean NYHA class
      at the end of follow-up was lower in OMC (1.14+/-0.3) versus PTMC (1.39+/-0.6)
      and MVR (1.41+/-0.71) (p=0.001). CONCLUSIONS: Even though conservative techniques
      are the first option to consider in treating mitral valve stenosis, valve
      replacement with bileaflet prostheses no longer represents a limiting factor to
      survival and quality of life.

PMID- 11471929
TI  - Blood pressure and urinary cations in a low-fat intake Chinese population sample.
AB  - BACKGROUND: The relationship between cation intake and blood pressure (BP) in
      populations with specific dietary habits such as a low fat intake, remains
      unclear. A low fat intake has been prevalent during human evolution. METHODS: The
      average of 6 BP readings and heart rate (HR) recordings has been calculated.
      Dietary intake was measured using the 24 h recall-method. A 24 h urine sample was
      collected. RESULTS: A highly significant correlation was found between the
      sodium/potassium ratio (Na/K), after adjustment for age, weight, height, heart
      rate, alcohol intake and sex and systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and pulse pressure (PP). The same applies to the sodium/creatinine
      (Na/Cr) and potassium/creatinine (K/Cr) ratios, with a positive correlation for
      Na/Cr and a negative one for K/Cr. The partial regression coefficient was in
      absolute value about 4-5 times greater for K/Cr than for Na/Cr. Age correlates
      highly significantly and independently with both SBP and DBP. CONCLUSION: If a
      Na/K ratio of 1 is considered optimal, by achieving that goal mean SBP could be
      reduced by about 6 mm Hg and mean DBP by 3 mm Hg in this normotensive population.

PMID- 11471930
TI  - Are women with acute myocardial infarction managed as well as men? Does it have
      consequences on in-hospital mortality? Analysis of an unselected cohort of 801
      women and 1,718 men.
AB  - OBJECTIVE: This study sought to compare characteristics and management of
      myocardial infarction in men and women, and whether a difference in management
      would translate into a difference in in-hospital mortality. METHODS AND RESULTS:
      Data were prospectively collected in 2,519 patients (801 women) admitted in all
      hospitals in three departments in the Rhjne-Alpes region in France between
      September 1, 1993 and January 31, 1995. Women were older than men (76 vs. 64
      years). The interval between symptom onset and initial medical intervention was
      longer in women than in men (median: 180 vs. 135 minutes), as was the interval
      between symptom onset and hospital admission (median: 315 vs. 255 minutes). After
      age-adjustment, women were less often smokers, and more often hypertensive or
      diabetic than men, location of infarction was more often anterior in women, as
      congestive heart failure at admission. In multivariate analysis, thrombolysis
      rate was not significantly different in both sexes, whereas noninvasive tests,
      coronary arteriography, percutaneous transluminal coronary angioplasty, and
      coronary artery bypass grafting were significantly less often performed in women
      than in men. Although in-hospital mortality was higher in women than in men (21%
      vs. 11%), this difference disappeared after age-adjustment (relative risk =
      0.99). In multivariate analysis, gender was not an independent predictor of
      survival. CONCLUSIONS: Although in-hospital mortality after myocardial infarction
      was similar in both sexes, rates of diagnostic and therapeutic procedures were
      lower in women than in men. This raises the question of whether mortality would
      decrease in women if management were similar in both sexes.

PMID- 11471931
TI  - Protective effect of PEG-SOD against early coronary reperfusion injury assessed
      in reperfused and non-reperfused ischaemic areas of the same heart.
AB  - OBJECTIVE: In order to investigate the salvage of ischaemic myocardium by
      polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), we compared
      reperfused and non-reperfused regions in the same canine heart and measured
      regional myocardial blood flow (RMBF) and myocardial CPK during coronary
      occlusion and reperfusion using non-radioactive, coloured microspheres. METHODS
      AND RESULTS: The chests of 17 mongrel dogs were opened under anaesthesia, and the
      left circumflex coronary artery was occluded for 90 min and then reperfused for 5
      min. During this procedure, polystyrene microspheres of different colours were
      infused at four different times: prior to occlusion (orange), 10 min (red) and 90
      min (blue) after occlusion, and 5 min after reperfusion (yellow). Thereafter, the
      heart was excised, cut in slices along the left circumflex coronary artery, and
      flow rates at the various times were assessed as a function of microsphere
      counts. In the control group (n=9), there are significant differences in the
      myocardial CPK level between reperfused and non-reperfused areas. The myocardial
      CPK level in reperfused area was significantly reduced compared to non-reperfused
      area in the outer layers (54 +/- 8 IU/g vs. 74 +/- 9 IU/g, P < 0.05), and also
      reduced in the inner layers (59 +/- 9 IU/g vs. 74 +/- 13 IU/g), however, it was
      not significantly different. In the PEG-SOD group (n=8), there was no significant
      difference in the myocardial CPK level between reperfused and non-reperfused
      areas in both inner and outer layers (inner layers; 68 +/- 11 IU/g vs. 68 +/- 6
      IU/g, outer layer; 69 +/- 17 IU/g vs. 67 +/- 18 IU/g), indicating a significant
      protective effect of PEG-SOD. In the control group, transmural necrosis of the
      reperfused areas was 22.4 +/- 10.0%, which showed no significant difference
      compared with non-reperfused areas (23.1 +/- 9.9%). In the PEG-SOD group,
      transmural necrosis of the reperfused areas by TTC staining was 8.1 +/- 8.1%,
      which showed no significant difference compared with non-reperfused areas (8.5 +/
      7.1%). CONCLUSIONS: PEG-SOD prevents infarct extension during early coronary
      reperfusion.

PMID- 11471932
TI  - Unstable angina due to spontaneous dissection of a LIMA graft.
AB  - We report a case of a spontaneous dissection of a left internal mammary artery
      grafted on the diagonal branch and the left anterior descendens. The clinical and
      diagnostic features of this condition are discussed. Despite an extensive
      literature search, no such case could be found. This case report must be regarded
      as the first. We speculate that extensive kinking of the left internal mammary
      artery contributed in the pathogenesis of this syndrome.

PMID- 11471933
TI  - Magnetic resonance diagnosis of lipomatous hypertrophy of the atrioventricular
      grooves mimicking a tumour on echocardiography.
AB  - Echogenic structures in the atrioventricular grooves may cause diagnostic
      problems and may be misinterpreted as a tumour. Images of lipomatous hypertrophy
      of the atrioventricular grooves diagnosed by magnetic resonance but mimicking a
      tumour on echocardiography are presented.

PMID- 11471934
TI  - Coronary artery to left ventricular fistula: case report and review of the
      literature.
AB  - In this report, an unusual case with a multiple plexiform type of coronary artery
      to-left ventricular fistula and coexisting atherosclerotic involvement of the
      contralateral coronary artery is described and the pertinent literature is
      reviewed briefly.

PMID- 11471935
TI  - A rare form of atrioventricular septal defect with severe subaortic stenosis.
AB  - An unusual form of atrioventricular septal defect associated with severe
      subaortic obstruction is reported in a neonate who presented with intractable
      cardiac failure. The baby had a large defect in the atrioventricular septum
      allowing communication from the left ventricle to the right atrium, without
      interatrial or interventricular communication, and a cleft anterior mitral
      leaflet. The baby expired despite palliative surgery performed to bypass the
      subaortic stenosis.

PMID- 11471936
TI  - Dilated coronary sinus mimicking posterior left ventricular aneurysm.
AB  - Dilation of the coronary sinus is mostly a congenital lesion. As acquired lesion
      it was found to be associated with poor left ventricular function. In the present
      case an angiographic diagnosed posterior left ventricular aneurysm was during
      surgery found to be a dilated coronary sinus. Preoperative left ventricular
      function was normal.

PMID- 11471937
TI  - Food processing by animals: do beavers leach tree bark to improve palatability?
AB  - Beavers store and consume tree parts in the bodies of water where they live. We
      examined whether such soaking renders food more palatable by leaching out
      undesirable compounds. In experiment 1, saplings of red maple, Acer rubrum (RM),
      were first soaked in a pond for periods of 2, 18, and 36 days, then offered to
      free-ranging beavers. Soaking for two days rendered RM slightly more acceptable
      to beavers. To further examine the time window around two days, RM sticks were
      soaked in distilled water in the laboratory for 1, 2, 4, and 6 days before
      presenting them to beavers (experiment 2). In experiment 3, twigs of three
      species were placed on land. Beavers placed RM in the water for 1 to 3 days
      before consuming the twigs. In experiment 4, sticks were provided in the water at
      Cranberry Lake Biological Station (CLBS). Most quaking aspen (QA) was consumed
      during the first night, and most witch hazel, Hamamelis virginiana (WH), during
      the third night. At Allegany State Park (ASP), no such difference was found.
      Twigs were provided in the water in experiment 5. At ASP, WH was taken after
      three days in the water, and at CLBS little WH was consumed, and only during the
      third night. A meta-analysis of all experiments shows that relatively more WH is
      consumed after two days than any other species. Experiment 6 traced the time
      beavers left their own harvested branches in the water. Unlike other tree
      species, WH remained in the water for two to four days before being consumed.
      Experiment 7 measured the phenolics leached into water from RM twigs and small
      pieces of bark soaked for 10 and 8 days, respectively. Shredded bark lost 50-60%
      of leachable phenolics into the water, and twigs 70-80%. We conclude that beavers
      can use water to leach undesirable compounds from their food. Although this
      effect was not robust, our study is the first of its kind.

PMID- 11471938
TI  - Laboratory and field evaluation of predator odors as repellents for kiore (Rattus
      exulans) and ship rats (R. rattus).
AB  - Predator odors may serve to stop rats from entering conservation areas or to
      decrease predation, food consumption, and other damage by rats in areas tainted
      with predator odor. We compared the efficacy of real predator odors and synthetic
      odors (derived from the urine and feces of carnivores) as rat repellents with
      real herbivore odors as controls in a Y maze. We tested six predator odors: cat
      (Felis catus) urine and feces, mongoose (Herpestes auropunctatus) feces, n
      propylthietane, S-methyl, methyl butanol, and isopentyl-methyl sulphide. The
      herbivore odors we used were: red deer (Cervus elaphus) urine, guinea pig (Cavia
      porcellus) feces, and white rabbit (Oryctolagus cuniculus) urine. Ship rats
      (Rattus rattus) and kiore or Polynesian rats (R. exulans) showed no aversion to
      any of the six predator odors when compared with herbivore odors. Ship rats,
      however, may have avoided synthesized odors more than real ones. We applied two
      odors (S-methyl, methyl butanol and n-propylthietane) to purpose-built feeders in
      native forest but recorded no change in either visitation rate or duration of
      visits for rodents [rats and mice (Mus musculus)] or possums (Trichosurus
      vulpecula). The consumption of maize at feeders was correlated with the number
      and duration of possum visits, but only weakly correlated with the number of
      visits by rodents. Consumption of maize was unaffected by the odor associated
      with the feeder. It is unlikely that the odors we tested will be useful in
      deterring rodents or possums from areas where they have been removed for
      economic, public health or conservation reasons.

PMID- 11471939
TI  - Effects of long-term open-field ozone exposure on leaf phenolics of European
      silver birch (Betula pendula Roth).
AB  - The response of phenolic compounds as a result of long-term low open-field ozone
      exposure was studied in ozone-sensitive and ozone-tolerant clones of European
      silver birch (Betula pendula Roth). The saplings were exposed to 1.5-1.6 times
      the ambient (elevated) ozone and ambient air (as control) over three growing
      seasons from May 1996 until August 1998. Quantification by modified Folin
      Ciocalteau assay showed a 16.2% increase in total phenolics in elevated ozone
      plants as compared to that in controls and a corresponding 9.9% increase of 10
      phenolic compounds quantified by HPLC. Five nonflavonoids and five flavonoids
      showed 8.4% and 11.4% increases, respectively. The phenolic results indicated
      slightly higher ozone sensitivity of clone 5 as compared to clone 2. The most
      ozone-responsive phenolic compounds in clone 2 and clone 5 were (+)-catechin
      (CT), chlorogenic acid (CGA), 5-p-coumaroylquinic acid (5CQA), 3-p
      coumaroylquinic acid (3CQA), myricetin galactopyranoside (MG), quercetin-3-O
      glucuronopyranoside (QGR), and quercetin-3-O-arabinofuranoside (QA). Increased
      phenolic content in ozone-exposed plants was related to impaired growth and
      accelerated leaf senescence, indicated by enhanced autumn leaf yellowing and
      lower chlorophyll and Mg content. The change in carbon allocation towards
      defensive phenolics at the expense of growth was greater in the ozone-sensitive
      clone as compared to tolerant clone.

PMID- 11471940
TI  - Nematode-antagonistic trichothecenes from Fusarium equiseti.
AB  - A strain of the fungus Fusarium equiseti isolated from soybean cyst nematode
      secretes nematode-antagonistic compounds. Bioassay-guided fractionation of an
      extract of the culture broth was undertaken to identify the compounds. Fractions
      were assayed for activity against a root-knot nematode (Meloidogyne incognita), a
      plant pathogen that attacks the roots of numerous plant species. Two
      trichothecene compounds were isolated that inhibited egg hatch and immobilized
      second-stage juveniles of this nematode: 4,15-diacetoxy-12,13-epoxy-3,7
      dihydroxytrichothec-9-en-8-one (4,15-diacetylnivalenol) and 4,15-diacetoxy-12,13
      epoxy-trichothec-9-en-3-ol (diacetoxyscirpenol). This is the first published
      report of these compounds affecting plant-parasitic nematodes.

PMID- 11471941
TI  - Olfaction in the Queensland fruit fly, Bactrocera tryoni. I: Identification of
      olfactory receptor neuron types responding to environmental odors.
AB  - The electroantennogram method was used to investigate the number of distinct
      olfactory receptor neuron types responding to a range of behaviorally active
      volatile chemicals in gravid Queensland fruit flies, Bactrocera tryoni. Three
      receptor neuron types were identified. One type responds to methyl butyrate, 2
      butanone, farnesene, and carbon dioxide; a second to ethanol; and a third to n
      butyric acid and ammonia. The receptor neuron type responding to methyl butyrate,
      2-butanone, farnesene, and carbon dioxide consists of three subtypes. The
      presence of a limited number of receptor neuron types responding to a diverse set
      of chemicals and the reception of carbon dioxide by a receptor neuron type that
      responds to other odorants are novel aspects of the peripheral olfactory
      discrimination process.

PMID- 11471942
TI  - Olfaction in the Queensland fruit fly, Bactrocera tryoni. II: Response spectra
      and temporal encoding characteristics of the carbon dioxide receptors.
AB  - Single-unit electrophysiology was used to record the nerve impulses from the
      carbon dioxide receptors of female Queensland fruit flies, Bactroera tryoni. The
      receptors responded to stimulation in a phasic-tonic manner and also had a period
      of inhibition of the nerve impulses after the end of stimulation. at high
      stimulus intensities. The cell responding to carbon dioxide was presented with a
      range of environmental odorants and found to respond to methyl butyrate and 2
      butanone. The coding characteristics of the carbon dioxide cell and the ability
      to detect other odorants are discussed, with particular reference to the known
      behavior of the fly.

PMID- 11471943
TI  - Evaluation of the synthetic major component of the sex pheromone of Tuta absoluta
      (Meyrick) (Lepidoptera: Gelechiidae).
AB  - In wind-tunnel bioassays, dispensers loaded with 1 microg of the synthetic major
      component (3E,8Z, 11Z)-3,8,11-tetradecatrienyl acetate (TDTA) of the sex
      pheromone emitted by Tuta absoluta (Meyrick) females were found to be highly
      attractive to conspecific males. Field experiments were conducted to evaluate the
      efficacy of five trap designs. The best trap, baited with 100 microg of the
      synthetic sex pheromone caught on average 1,200 males per trap per night, while
      those baited with virgin females caught only 201 males. The male response to this
      pheromone is restricted to the same early-morning time window during which
      females exhibit calling behavior. The high biological activity of the synthetic
      pheromone suggests that it could be useful for pest monitoring and in mating
      disruption.

PMID- 11471944
TI  - Task-related chemical analysis of labial gland volatile secretion in worker
      honeybees (Apis mellifera ligustica).
AB  - Chemical analyses revealed that the labial gland complex of worker honeybees
      possesses a series of hydrocarbons dominated by odd-numbered carbon chain alkanes
      along with minor amounts of alkenes and branched alkanes. Foragers contained
      significantly more secretion than nurse bees. Experiments with bees from colonies
      induced to have a division of labor independent of age revealed that the
      differences in the amount of secretion were task, but not age dependent.

PMID- 11471945
TI  - Segregation of colony odor in the desert ant Cataglyphis niger.
AB  - There are two separate, and presumably opposing, processes that affect colony
      odor in the desert ant Cataglyphis niger: (1) biosynthesis and turnover of these
      chemicals by individual ants, and (2) homogenization of colony odor through
      exchange of cues. The first increases signal variability; the latter decreases
      it. The impact of these factors was tested by splitting colonies and monitoring
      the profile changes occurring in the postpharyngeal glands (PPG) and cuticular
      hydrocarbons. From each of two polygynous nests four daughter colonies were
      formed, three monogynous and one queenless. Thereafter, 10 ants from each were
      randomly selected each month, for three successive months, for analyses of their
      PPG and cuticular hydrocarbons. From two colonies we also obtained ants from a
      known matriline. Over time, there was a shift in hydrocarbon profiles of both the
      PPG and cuticular washes in each of the tested colonies. Moreover, by subjecting
      selected hydrocarbon constituents to a discriminant analyses based on their
      relative proportions, all of the daughter colonies (queenright and queenless)
      were distinguishable from each other and from their respective mother colonies.
      In each of the queenright daughter colonies, the queen profile was
      indiscriminable from that of the workers and often was in the center of the
      group. Full sisters were clearly distinguishable from their nestmates,
      emphasizing the genetic versus environmental processes that govern colony odor.
      The effect of time was always superior to the separation effect in contributing
      to odor segregation. Comparison of the Mahalanobis distances indicated that the
      shift in hydrocarbon seems to proceed along parallel lines rather than in
      divergence. However, there was no overt aggression between ants that originated
      from the different subgroups in dyadic encounters. It appears that in this
      species a three-month separation pe riod is not sufficient to change the
      hydrocarbon profile beyond the recognition threshold.

PMID- 11471946
TI  - Absolute configuration of anabasine from Messor and Aphaenogaster ants.
AB  - A method has been developed to assign the absolute configuration and enantiomeric
      excess of anabasine based on small amounts of material (in the microgram range),
      by derivatization with (+)-menthylchloroformate followed by capillary GC analysis
      of the resulting carbamate(s). This method was applied to three samples of
      anabasine isolated from Messor and Aphaenogaster ants. In Messor sanctus, only
      (2'S)-anabasine was present, whereas in Aphaenogaster subterranea and A. miamiana
      (2'S)-anabasine was determined to have an ee of 78 and 24%, respectively.

PMID- 11471947
TI  - Allomonal and hepatotoxic effects following methyl eugenol consumption in
      Bactrocera papayae male against Gekko monarchus.
AB  - Methyl eugenol (ME), is converted into two major phenylpropanoids, 2-allyl-4,5
      dimethoxyphenol and trans-coniferyl alcohol, following consumption by the male
      fruit fly Bactrocera papayae. Chemical analysis of wild male B. papayae rectal
      glands, where the compounds are sequestered, revealed the presence of ME
      metabolites in varying quantities. These phenylpropanoids are shown to be
      involved in the fruit fly defense both in no-choice and choice feeding tests
      against the Malayan spiny gecko, Gekko monarchus. After being acclimatized to
      feeding on fruit flies, geckos consumed significantly fewer ME-fed male flies
      than controls that consumed all the ME-deprived male flies offered throughout a
      two-week period. Diagnosis of dissected livers from geckos that consumed ME-fed
      male flies revealed various abnormalities. These included discoloration and
      hardening of liver tissue, whitening of the gallbladder, or presence of tumor
      like growths in all geckos that consumed ME-fed male flies. Control geckos fed on
      ME-deprived male flies had healthy livers. When given an alternative prey, geckos
      preferred to eat untreated house flies, Musca domestica to avoid preying on ME
      fed fruit flies.

PMID- 11471948
TI  - Effects of isoflavonoids from Cicer on larvae of Heliocoverpa armigera.
AB  - Four recently identified isoflavonoids, isolated from wild relatives of chickpea,
      Cicer arietinum, were shown to deter larval feeding by Heliocoverpa armigera at
      100 ppm, judaicin and maackiain retained their antifeedant activity at 50 ppm and
      10 ppm, respectively. The isoflavonoids were tested in combinations and with
      chlorogenic acid; the combinations containing judaicin and maackiain were most
      active, and chlorogenic acid enhanced the antifeedant activity of all four
      isoflavonoids. H. armigera was the only one of four noctuids to be deterred by
      all four isoflavonoids. Spodoptera littoralis was deterred by judaicin alone and
      S. frugiperda by maackiain alone. Heliothis virescens and S. exigua were not
      deterred from feeding by any of the isoflavonoids. When incorporated into a diet,
      isoflavonoids decreased the weight gain of early stadia larvae of H. armigera
      more than they did later stadia, and maackiain and judaicin were most potent. We
      conclude that the isoflavonoids. especially maackiain and judaicin, could play a
      role in decreasing the susceptibility of Cicer to attack by H. armigera.

PMID- 11471949
TI  - Response of brown treesnakes (Boiga irregularis) to mammalian blood: whole blood,
      serum, and cellular residue.
AB  - Brown treesnakes (Boiga irregularis) responded with more tongue flicks to blood
      (from rabbits, rats, and mice) than to water. When rat blood was centrifuged at
      3,500 rpm for 5 min, separating serum from cellular residue, snakes responded
      strongly to serum but not to cellular residue.

PMID- 11471950
TI  - Host finding and oviposition behavior in a chrysomelid specialist--the importance
      of host plant surface waxes.
AB  - Although several studies have elucidated the role of plant epicuticular waxes in
      host recognition and oviposition by herbivorous insects, there is little known
      about this subject in Chrysomelidae. In the present study, chemical cues for host
      recognition behavior and oviposition by the monophagous chrysomelid species
      Cassida stigmatica were investigated with special regard to surface waxes of the
      host plant. Tanacetum vulgare (Asteraceae). After hibernation in the soil, adults
      of this species must climb the plant's petioles, which emerge from the ground in
      spring. The response of adult C. stigmatica to contact and volatile cues from
      petioles and leaves of T. vulgare was investigated in a "stem arena," in which
      differently treated petioles and petiole dummies were offered. Volatile and
      contact cues of T. vulgare petioles served as well for host recognition. The
      contact cues were isolated from the petioles and leaves by hexane extraction and
      by cellulose acetate treatment, which removed cuticular waxes. The attractive
      volatiles were not extracted sufficiently by hexane. To examine the role of
      cuticular waxes of the host leaf surface in oviposition, female C. stigmatica
      were offered intact leaflets and leaflets from which cuticular waxes had been
      stripped by cellulose acetate treatment. Females did not discriminate between
      intact and stripped leaflets when only the upper leaf surfaces were offered.
      However. when the lower leaf surfaces that are generally used as oviposition
      sites were offered, C. stigmatica preferred to lay eggs on intact leaflets. We
      conclude that waxes of the lower leaf surface contain crucial information for
      oviposition in C. stigmatica.

PMID- 11471951
TI  - Olfactory responses of Ips duplicatus from inner Mongolia, China to nonhost leaf
      and bark volatiles.
AB  - Leaf and bark volatiles from nonhost angiosperm trees were tested on Ips
      duplicatus by gas chromatographic-electroantennographic detection (GC-EAD) and by
      pheromone-baited traps in Sweden and Inner Mongolia, China, respectively. GC-EAD
      analysis of the headspace volatiles from fresh bark chips of Betula pubescens
      revealed trans-conophthorin, two green leaf volatiles (GLVs): 1-hexanol and (Z)-3
      hexen-1-ol, and two C8 alcohols: 3-octanol and 1-octen-3-ol, that consistently
      elicited antennal responses by I. duplicatus. The identification of these EAD
      active compounds was confirmed in further GC-EAD recordings with synthetic
      mixtures. Antennal responses were also found to synthetic (E)-2-hexen-1-ol and
      linalool, which have been identified from the leaves of nonhost birch and aspen
      species. No antennal responses of I. duplicatus were found to hexanal, (E)-2
      hexenal, and (Z)-3-hexyl acetates. In field trapping experiments, blends of EAD
      active green leaf alcohols or C8 alcohols, or transconophthorin alone resulted in
      significant reductions (27-60%) in the number of I. duplicatus captured compared
      with pheromone-baited traps. The unsuitable host compound, verbenone (Vn), also
      significantly reduced trap catches by up to 60% in both experiments. The
      strongest disruptive effect resulted from the addition of the combination of
      green leaf alcohols, C8 alcohols, and verbenone to the pheromone trap, which
      caused an 84% reduction in trap catch. The blend of two green leaf aldehydes plus
      the acetate increased the trap catches in 1998 and had no negative or positive
      effects in 1999. Our results suggest that these nonhost volatiles (NHVs) are
      important olfactory signals used by I. duplicatus in host selection. They may
      have great significance in developing semiochemical-based management programs for
      I. duplicatus by reducing or stopping attacks on suitable hosts.

PMID- 11471952
TI  - A surgical perspective from two decades of breast augmentation: toward state of
      the art in 2001.
AB  - This article summarizes the author's perspective of two decades of breast
      augmentation based on clinical experience using virtually every type of implant,
      incision location, pocket location, dissection technique and instrumentation
      available from 1977 to 2001. Based on this experience, the author focuses on
      patient education, the importance of patient choice, patient evaluation and
      preoperative planning, surgical techniques, patient recovery, and factors to
      limit reoperations.

PMID- 11471953
TI  - Alternative filler materials and new implant designs: what's available and what's
      on the horizon?
AB  - Despite ample evidence that silicone gel-filled implants do not cause systemic
      illness, they are still not available in the United States for widespread use. At
      this point, saline-filled implants are widely available for use, and assuming
      favorable outcomes of the relevant silicone studies, some forms of silicone gel
      filled implants could be approved by the FDA and be available as soon as 2003.
      Other products under preliminary consideration by the FDA for eventual studies
      include the 150 series and the cohesive silicone gel-filled 410 series by McGhan,
      and the NovaGold implant by NovaMed. Assuming favorable study results, one or
      more could be approved by the FDA by the year 2004. Any products not yet
      submitted to the FDA for review of study designs by this time are not likely to
      be available in the United States in the next 4 or 5 years.

PMID- 11471954
TI  - Saline breast implant fill issues.
AB  - Plastic surgeons' primary responsibility to patients is to inform them
      sufficiently to permit them to make the necessary decisions in the manner that
      best meets their own objectives. This makes adequate consultation a lengthy and
      often confusing experience for patients. One of the most confusing of these is
      also one of the most mandatory for discussion; that is, the issue of implant fill
      volume. A patient should be free to choose between an implant that must be
      overfilled to achieve the optimum, and one in which reaching the optimum does not
      require overfill or even staying within the manufacturers suboptimal fill volume.
      The patient must be explicitly informed of the consequences of each of these
      decisions and should be prepared to sign whichever consents are necessary to
      reflect her understanding of the compromises involved in any of these choices.

PMID- 11471955
TI  - Breast implant research: where we have been, where we are, where we need to go.
AB  - This article summarizes the current state and future needs of research into
      saline-filled and silicone gel breast implants. The authors describe recent
      investigations into possible causes and potential risk factors for silicone gel
      and saline implant failure. Also discussed are local complications of breast
      implantation and the need for revisional operations in augmentation and
      reconstruction patients. In addition, the effects that surgical, implant, and
      patient variables have on the aesthetic outcome of surgery are addressed. The
      last portion of the article lays out future research needs, such as determining
      the incidence rate of implant failure, reducing the frequency of revisional
      surgery, and the difficulty of designing better breast implants in the current
      strict regulatory climate.

PMID- 11471956
TI  - Alternatives and trade-offs in breast augmentation.
AB  - Selection of alternatives for breast augmentation should be prioritized in the
      order in which those selections are most likely to affect short- and long-term
      outcomes. Every selection of alternative must be reconciled with patient
      priorities and patient tissue limitations. This discussion addresses selection of
      alternatives for breast augmentation sequenced in order of priority, including
      the following: assuring adequate soft tissue coverage (pocket location), implant
      size and type, patient tissue limitations, long-term implant-soft tissue
      dynamics, incision approach, intraoperative techniques and instrumentation to
      optimize control, and intraoperative techniques to minimize tissue trauma.

PMID- 11471957
TI  - Patient evaluation, operative planning, and surgical techniques to increase
      control and reduce morbidity and reoperations in breast augmentation.
AB  - Current rates of reoperations and complications in augmentation mammaplasty are
      unacceptably high and can be improved. Risks, trade-offs, complications,
      morbidity, time to recovery, and reoperation rates in breast augmentation can be
      improved substantially by stringent patient selection, thorough tissue
      evaluation, implant selection based on tissue characteristics, and selection of
      pocket location and surgical techniques.

PMID- 11471958
TI  - Breast augmentation with round, smooth saline or gel implants: the pros and cons.
AB  - Breast augmentation is a procedure that can be performed successfully in many
      different ways. Large series are reported routinely, with greater than 95%
      patient satisfaction. It is clear that this is a procedure that has greatly
      benefited women and thereby society in general. It is inappropriate to be too
      dogmatic about each individual's technique, because many different techniques
      have achieved a high degree of success in terms of patient satisfaction and final
      results. That is not to say, however, that surgeons still are not plagued by the
      two most common downsides to this operation: capsular contracture and implant
      leakage. Certainly, strides have been made in the cause of prevention of capsular
      contracture in the past 20 years of the author's association with plastic
      surgery, but the author's opinion is that research has been hampered by the Food
      and Drug Administration's overprotection of women. There is no doubt that
      progress toward solving these two problems has been slowed by the current implant
      environment. Despite these handicaps, however, plastic surgery has continued to
      improve this procedure and now is delivering a successful and reproducible
      surgery using the saline implant. Most surgeons doubted this in the early 1990s,
      however. Plastic surgeons must continue to strive for improvements that serve
      patients and themselves in this new century.

PMID- 11471959
TI  - Breast augmentation with anatomical cohesive gel implants: the world's largest
      current experience.
AB  - Anatomic cohesive silicone gel implants in breast augmentations require a
      considerably different technique compared with standard round implants. If the
      dimensions and proportions of the thorax and breast and thus the prerequisite for
      different implant shapes are evaluated adequately, this newer technique can lead
      to highly predictable results with a high degree of patient satisfaction.

PMID- 11471960
TI  - Experience with anatomic breast implants.
AB  - Anatomic implants provide useful alternatives to breast augmentation for the
      discerning surgeon, particularly in breasts with tight skin envelopes or
      deficient lower poles.

PMID- 11471961
TI  - Breast augmentation with reduced-height anatomic implants: the pros and cons.
AB  - The reduced-height anatomic saline-filled implant has certain advantages. It has
      a distinct footprint and profile that allows the creation of a breast with
      relatively exaggerated width and abbreviated height. This creation suits certain
      anatomic situations and often is preferred by women seeking a more natural
      looking augmentation, without excessive upper pole fullness. The use of any
      anatomic design implant requires some dimensional planning and more precise
      pocket dissection. Although the risk for rotational deformities could be expected
      to be increased, clinically significant rotational deformities have not been a
      major problem.

PMID- 11471962
TI  - Breast augmentation with full-height anatomic saline implants: the pros and cons.
AB  - Full-height anatomic implants, like round implants, have advantages and
      disadvantages. Based on 21 years' experience using round implants and 10 years'
      experience using anatomic implants, the author believes that anatomically shaped
      implants offer substantial, significant advantages compared with round implants
      in more than 90% of primary augmentations. Anatomic implants are a significant
      addition to the armamentarium of any surgeon who performs primary breast
      augmentation, provided that the surgeon is willing to meet requirements for
      optimal use of these more sophisticated products: more stringent implant
      selection based on individual patient tissue characteristics, accurate pocket
      dissection under direct visualization, accurate implant positioning based on
      measured and visual parameters, and above all, detailed patient informed consent
      about the trade-offs of all implant options. Absent the willingness and skills
      development to meet these requirements, surgeons should avoid using anatomic
      implants.

PMID- 11471963
TI  - The polyurethane-covered mammary prosthesis: facts and fiction (II): a look back
      and a "peek" ahead.
AB  - The senior author believes that there is a niche for polyurethane-covered devices
      in the new millennium if they in fact become available. During the span of this
      author's practice, he has never been able to match the number and quality of
      superior results exemplified by these patients when using other devices. Women
      seeking reconstruction after mastectomy or aesthetic improvement will be well
      served if the polyurethane-covered device once again becomes one of the choices
      of mammary prostheses available to them, in this author's opinion.

PMID- 11471964
TI  - Complications in breast augmentation: prevention and correction.
AB  - The decision-making process for breast augmentation begins at the initial
      consultation. Most complications can be avoided with careful planning and
      decision making. Primary augmentation demands a careful evaluation of the breast
      morphology and chest wall anatomy. Perioperative techniques such as precise
      dissection of the pectoralis muscle under direct vision can ensure an adequate
      pocket, which minimizes the risk for capsular contracture and implant
      malposition. Secondary breast augmentation for problems such as thinning of the
      breast skin envelope, long-term pressure atrophy of existing parenchyma, and
      visibility of the implant can be minimized with appropriate selection of implant
      type, size, and placement. Patients should understand clearly the immediate and
      long-term risks associated with breast augmentation and the requirement for
      future reoperation.

PMID- 11471965
TI  - Transumbilical breast augmentation (TUBA): patient selection, technique, and
      clinical experience.
AB  - The TUBA procedure offers another approach to placing inflatable breast implants
      in the subglandular or submuscular position. It is an easy procedure to learn and
      to perform, using only a few relatively inexpensive specialized instruments. It
      also can be modified to use preexisting scars on the abdomen as the access point.
      The authors believe that complications seem to occur less with TUBA patients than
      with patients having breast augmentation by other approaches, an observation
      shared by other plastic surgeons offering the TUBA procedure. Limitations include
      the fact that only inflatable implants can be used. Also, with increasing
      distance from the breast, there is less control over manipulation of the pocket.
      Fortunately, the authors have not found this to be a problem in achieving
      symmetry. Furthermore, bleeding tends to be minimal with this approach.
      Nevertheless, should technical difficulties arise, conversion to a standard
      breast incision is an easy back-up option and should be discussed with the
      patient before surgery. Interest in the TUBA approach to breast augmentation
      continues to grow. Patients appreciate the lack of scarring on the breast and the
      short recovery that allows them to resume their normal lifestyle quickly. The
      authors' caseload has increased considerably over the past 8 years through word
      of-mouth advertising from satisfied patients. Other plastic surgeons who offer
      this approach agree that patient demand for this operation continues to grow
      dramatically in their practices.

PMID- 11471966
TI  - Preventing litigation in breast augmentation.
AB  - To obtain patient satisfaction and thus avoid exposure to liability claims in
      breast augmentation, the plastic surgeon must take pains to exert not only his or
      her surgical competence but also his or her medicolegal awareness. The recent
      breast implant crisis should have taught everyone a lesson. The surgeon should
      remember that the American legal system has more to do with showmanship than with
      justice, fairness, science, or truth. It is unlikely that anyone beginning a 30-
      to 40-year career in aesthetic surgery will finish it without an encounter with
      the US legal system. Surgeons should supplement their CME with "DME" (defensive
      medicine expertise). Only by cultivating the absolutely crucial elements of
      patient rapport will surgeons be able to stay one step ahead of the plaintiff's
      attorney.

PMID- 11471967
TI  - Caries and salivary status in young adults with type 1 diabetes.
AB  - The aim of this study was to evaluate the salivary status, prevalence of caries
      and the status of primary dentition, when primary teeth were exfoliated, in 41
      patients, 18-24 years of age, with type 1 diabetes since childhood in comparison
      with age- and sex-matched non-diabetic controls. The blood glucose and
      glycosylated haemoglobin concentration (HbA1c), dosage of daily insulin and
      retinal fundus photography was recorded for the diabetic group. According to the
      concentration of HbA1c, the diabetic patients were divided into well and poorly
      controlled groups. The study was based on three intra-oral photos, dental
      examination including intra-oral radiographs, flow rate and buffering capacity of
      the saliva and amount of Streptococcus mutans and Lactobacilli. Retrospective
      data regarding the primary dentition was found in the dental files of each
      patient, and are based on the last registration for respective tooth before
      exfoliation. The patients with type 1 diabetes, without any relationship to
      metabolic control, displayed more initial buccal caries compared to healthy
      controls (p<0.01). No significant differences concerning the status of saliva
      (neither flow rate, buffering capacity nor amount of Streptococcus mutans and
      Lactobacilli), manifest caries or the status of the primary dentition were seen.
      We conclude that initial, but not manifest caries seems to be overrepresented in
      young adults with type 1 diabetes. These patients, thus, need more intense
      efforts regarding dental health care to prevent the development from initial to
      manifest caries.

PMID- 11471968
TI  - Long-term evaluation of a fissure sealing programme in Public Dental Service
      clinics in Sweden.
AB  - The aim of the present study was to evaluate the long-term results of a
      systematic fissure sealing programme of the occlusal surfaces of newly erupted
      permanent first molars. All 15-year-olds (n=815) who had been regularly treated
      at seven Public Dental Service clinics in Jonkoping County, Sweden, since the
      eruption of their permanent first molars participated in the study. Data on
      fissure sealing and restorative treatment were extracted from the dental records
      of the patients. When the patients were 15 years of age, it was found that 6% of
      the original 2456 sealed occlusal permanent first molars had received Class II
      restorations. Seventy-eight per cent of the remaining 2322 sealed occlusal
      surfaces were judged to be caries-free by the child's ordinary dentist. This long
      term retrospective study indicates that a structured fissure sealing programme is
      of great benefit for oral health.

PMID- 11471969
TI  - Dentists' perception of risks for molars without antagonists. A questionnaire
      study of dentists in Sweden.
AB  - The aim of this questionnaire study was to investigate dentists' assessment of
      and the decision making process in a clinical situation with unopposed molar
      teeth. The questionnaire comprised, besides questions about the dentist's
      background, a presentation of a clinical situation with a 42-year old male
      patient who just had lost the left mandibular molars (teeth 36 and 37). A series
      of questions was provided with multiple choice answers regarding what most
      probably would occur with the unopposed maxillary molars within a 10-year period,
      what treatment to propose in such a situation, and indications for the proposed
      treatment. The questionnaire was sent to a randomly selected group of active
      members of the Goteborg Dental Society. Two hundred completed questionnaires were
      returned (response rate 72.5%). The great majority (85%) suggested that marked
      overeruption of the unopposed molars would occur, whereas 13% believed in minor
      changes. Almost half of the respondents (47%) proposed to wait and see before any
      treatment was started, whereas the remaining dentists wanted to perform some
      therapy as soon as possible or within a specified period of time. The most
      commonly suggested indications for treatment were risk for overeruption (79%),
      risk for impaired masticatory function (54%), and risk for development of TMD
      (50%). Differences in answers were found between female and male dentists,
      between specialists and general practitioners, and with respect to year of
      graduation. Most dentists believed that overeruption would occur in spite of the
      limited knowledge of what will happen to unopposed teeth.

PMID- 11471970
TI  - An 8-year follow-up of removable partial denture treatment performed by the
      Public Dental Health Service in a Swedish county.
AB  - The aim of the present study was to evaluate clasp-retained removable partial
      dentures (RPDs) made in the Public Dental Health Service (PDHS) in Orebro County
      in 1989. Records from all 25 PDHS clinics concerning RPDs from 1989 were
      collected after eight years and available information was registered. The entire
      material consisted of 447 RPDs (both attachment-retained and clasp-retained RPDs)
      in 387 patients. Of the 316 clasp-retained RPDs that were traceable, 208 were
      followed from 1989 to 1997. In most instances, information on diagnoses,
      alternative treatments and design of the RPDs was lacking. One hundred and thirty
      two (42%) of the 316 clasp-retained RPDs were judged to still be in use in 1997
      while 75 were not in use. The main reason for ceased use was dislike by the
      patient. There were 108 clasp-retained RPDs that were not possible to follow from
      1989 to 1997 because there were no notes regarding follow-ups in the records. The
      most common technical complications noted in the records during the observation
      period were clasp fractures and loosened artificial teeth.

PMID- 11471971
TI  - Analysis of caries status development in relation to socio-economic variables
      using a case-based system.
AB  - The aim of this study was to detect, using case-based reasoning (CBR) induction
      methods in time series analysis, how measurable socio-economical adjustments were
      related to the caries status development. The study concerned the year classes
      leaving the organised dental care for the time period 1987-95, and had received
      dental care at the Public Dental Service of Goteborg. The results, as presented
      by a caries incidence index, indicated that at least one socioeconomical factor,
      individuals seeking employment, was of importance for the caries status
      development, a factor with an increase of considerable proportions since 1990.
      The findings indicated that the other socio-economic variables used did not have
      the same importance for the caries status development. One feasible explanation
      is that these factors reflect more upon the social family situation than the
      economical. If the caries status reflects the social situation of the individual
      more than the economical, this argument will elucidate the reasoning. Using CBR
      for the analysis of relationships between oral disease and parameters possibly
      influencing health development has proven to be a valuable tool and complement to
      more traditional statistical methods. The analysis can make relationships
      explicit through the hierarchic knowledge trees and also show redundant
      information, attributes not appearing in the trees.

PMID- 11471972
TI  - Ribozyme genes protecting transgenic melon plants against potyviruses.
AB  - Potyviruses are the most important viral pathogens of crops worldwide. Under a
      contract with Gene Shears Pty Limited, we are using ribozyme genes to protect
      melon plants against two potyviruses: WMV2 and ZYMV. Different polyribozyme genes
      were designed, built and introduced into melons plants. Transgenic melon plants
      containing a resistance gene were obtained and their progeny was challenged by
      the appropriate virus. Most of the genes tested conferred some degree of
      resistance to the viruses in glasshouse trials. Melon plants from one family
      containing one gene directed against WMV2 were also field-trialed on small plots
      under natural infection pressure and were found immune to WMV2. Field trial is in
      progress for plants containing genes against ZYMV. Some of the ribozyme genes
      used in the plants were also assayed in a transient expression system in tobacco
      cells. This enabled us to study the sequence discrimination capacity of the
      ribozyme in the case of one ribozyme target site. We found that a mutated target
      GUG (non cleavable) was less susceptible to inhibition by the ribozyme gene than
      the corresponding wild type target GUA (cleavable). Work is now in progress to
      incorporate multiple resistance genes in melon plants, in constructs designed in
      compliance with the evolving European regulations concerning transgenic plants.
      The use of ribozyme genes to protect plants against viruses provides an
      alternative to the technologies currently used for protecting crops against
      viruses, based on the concept of Pathogen Derived Resistance (see for example
      14). In the light of concerns expressed by some plant virologists (13) about the
      use of viral genes in transgenic plants, it may be that ribozyme genes will find
      many uses in this area of agricultural biotechnology.

PMID- 11471973
TI  - Virulence properties of oral bacteria: impact of molecular biology.
AB  - Dental caries and periodontitis, although generally not life threatening, are
      nevertheless of significant importance. An understanding of the molecular nature
      of these diseases could aid the development of novel methods of prevention and
      control, and increase our knowledge of their etiology. The identification of
      virulence factors in oral bacteria could lead to the development of vaccines
      directed against these organisms, the design of inhibitors of biofilm formation,
      and the development of replacement therapy strategies.

PMID- 11471974
TI  - Introduction to the field of cytometry and its importance in biomedicine.

PMID- 11471975
TI  - Flow cytometry: principles and instrumentation.

PMID- 11471976
TI  - Stress in 1st-year women teachers: the context of social support and coping.
AB  - The effects of adverse work environments were examined in the context of other
      risk/protective factors in this extension of a short-term longitudinal study
      involving 184 newly appointed women teachers. Regression analyses revealed that
      adjusting for preemployment levels of the outcomes and negative affectivity
      social support and adversity in the fall work environment were among the factors
      that affected spring depressive symptoms, self-esteem, job satisfaction, and
      motivation to teach. Support from nonwork sources was directly related to future
      improved symptom levels and self-esteem; supervisor and colleague support were
      directly related to future job satisfaction. Effects of occupational coping,
      professional efficacy, locus of control, and school factors (e.g., special vs.
      regular education) were largely nonsignificant. Structural equation analyses
      indicated that adverse working conditions began to seriously affect the women
      soon after they started teaching.

PMID- 11471977
TI  - A search for parenting style: a cross-situational analysis of parental behavior.
AB  - Cross-situational stability in parents' emotional warmth and guidance was studied
      by observing parents (N = 77, M age = 38 years) with their school-aged child in 2
      dyadic problem-solving situations and in a family discussion concerning a moral
      dilemma. The observational data were coded by independent observers using
      dimensional ratings and dichotomous frequency counts as the 2 coding procedures.
      These procedures yielded a similar pattern of findings. Parents tended to behave
      consistently across situations, although the type of situation did affect the
      amount of emotional warmth and guidance manifested by the parent. Stability was
      further analyzed by means of structural equation modeling to test whether
      variance in parents' emotional warmth and guidance across situations was
      attributable to a generalized parenting style factor. A Parenting Style factor
      was identified that reflected the parents' child-centeredness; this factor
      explained, in part, parental behavior within each situation, although contextual
      factors also contributed to situation-specific variations from task to task.

PMID- 11471978
TI  - Effects of accelerated reading rate on syntactic processing of Hebrew sentences:
      electrophysiological evidence.
AB  - The present study was designed to investigate whether accelerated reading rate
      influences the way adult readers process sentence components with different
      grammatical functions. Participants were 20 male native Hebrew-speaking college
      students aged 18-27 years. The processing of normal word strings was examined
      during word-by-word reading of sentences having subject-verb-object (SVO)
      syntactic structure in self-paced and fast-paced conditions. In both reading
      conditions, the N100 (late positive) and P300 (late negative) event-related
      potential (ERP) components were sensitive to such internal processes as
      recognition of words' syntactic functions. However, an accelerated reading rate
      influenced the way in which readers processed these sentence elements. In the
      self-paced condition, the predicate-centered (morphologically based) strategy was
      used, whereas in the fast-paced condition an approach that was more like the word
      order strategy was used. This new pattern was correlated with findings on the
      shortening of latency and the increasing of amplitudes in both N100 and P300 ERP
      components for most sentence elements. These changes seemed to be related to
      improved working memory functioning and maximized attention.

PMID- 11471979
TI  - Academic, motivational, and emotional correlates of adolescent dating.
AB  - This study is an examination of the relationship between dating status and
      academic achievement, academic motivation, depression, and self-esteem; it is an
      investigation of the differential effects wielded by gender and age (grade level)
      of the dating adolescent in each of these domains. Participants were a relatively
      large gender-balanced adolescent group (N = 380) from Grades 8, 10, and 12.
      Dating status was studied first as a binary variable (frequent versus infrequent
      dating) and second as a dating spectrum, including steady, frequent, and
      infrequent dating. Results showed that adolescents who dated frequently (more
      than once or twice a month), whether they were boys or girls, relatively young
      (8th grade) or more mature (l0th and 12th grades), exhibited consistently and
      significantly lower levels of academic achievement and academic motivation and
      higher levels of depressive symptoms. There were no significant effects of dating
      status on global self-esteem, but, as hypothesized, subscale analyses revealed
      important subscale-differentiated effects.

PMID- 11471980
TI  - A phase II trial testing the thermal dose parameter CEM43 degrees T90 as a
      predictor of response in soft tissue sarcomas treated with pre-operative
      thermoradiotherapy.
AB  - We prospectively evaluated whether delivering a thermal dose of > 10 cumulative
      equivalent minutes at 43 degrees C to >90% of the tumour sites monitored (CEM43
      degrees T90) would produce a pathologic complete response (pCR) in > 75% of high
      grade soft tissue sarcomas treated pre-operatively with thermoradiotherapy. The
      impact of thermal dose on local failure (LF), distant metastasis (DM), and
      toxicity was also assessed. Thirty-five patients > or = 18 years old with grade 2
      or 3 soft tissue sarcomas accessible for invasive thermometry were enrolled on
      the protocol. All patients received megavoltage external beam radiotherapy (RT)
      in daily fractions of 1.8-2.0 Gy, five times a week, to a median total dose of 50
      Gy and an initial hyperthermia treatment (HT) of I h duration utilizing the BSD
      2000 with Sigma 60 or MAPA applicators at frequencies of 60-140 MHz. Further HT
      was given for patients with CEM43 degrees T90 > 0.5 after initial HT ('heatable'
      patients), twice a week to a maximum of 10 HT or CEM43 degrees T90 > 100. Of the
      35 patients entered, 30 had heatable tumours, one of which was inevaluable for
      pCR or LF as the patient died of DM prior to surgery, leaving 29 evaluable
      patients. Of these 29 patients, 15 (52%) had a pCR (95% CI: 37-73%),
      significantly less than the projected rate of > or = 75% (p = 0.02). Of the 25
      heatable tumours that achieved CEM43 degrees T90 > or = 10, 14 (56%) had a pCR
      (95% CI: 39-78%) significantly less than the projected rate (p = 0.06). Three of
      the 29 patients (10%) with heatable tumours had a LF, versus 1/5 unheatable
      tumours (p = 0.48). Fourteen of the 30 patients (47%) with heatable tumours
      developed DM, versus 2/5 unheatable tumours (p = 1.00). Ten of the 30 patients
      (33%) with heatable tumours developed treatment-induced toxicity. Thus, no
      correlation of thermal dose with histologic response was observed. Prospective
      control of CEM43 degrees T90 failed to achieve the projected pCR rate following
      pre-operative thermoradiotherapy for high-grade soft tissue sarcomas, despite
      excellent local control. Possible explanations for this outcome are discussed.

PMID- 11471981
TI  - Thermoradiotherapy for locally recurrent breast cancer with skin involvement.
AB  - PURPOSE: This retrospective analysis investigated the effectiveness and side
      effects of combined hyperthermia and radiation therapy in locally recurrent
      breast cancer after primary modified radical mastectomy. The aim of the
      thermoradiotherapy was to reduce the substantial risk of symptomatic chest wall
      disease. MATERIALS AND METHODS: Between May 1995-August 1998, 39 extensively pre
      treated women with progressive locoregional chest wall tumours were treated with
      local radiofrequency hyperthermia, given twice a week immediately before
      radiotherapy. Sixty-two per cent of the patients had received previous
      radiotherapy, with a median dose of 50 Gy, 64% had received chemotherapy, 36%
      hormonal therapy, and 13% local therapy with miltefosin, respectively. Nine
      patients were treated for microscopic residual disease after local tumour
      excision (R1-resection) and 30 patients for gross macroscopic nodular
      recurrences. Twenty-seven patients had two adjacent hyperthermia fields at the
      ipsilateral chest wall to cover the whole irradiation area. Each field received a
      median of seven local hyperthermia sessions (range 2-12, average 5.6 sessions)
      just before radiation therapy, with a median dose of 60 Gy (range 30-68 Gy). The
      monitored maximum(average) and average(average) epicutaneous temperatures were
      42.1 degrees C and 41.0 degrees C, respectively. Maximum(average) and
      average(average) intratumoural temperatures of 43.0 degrees C and 41.1 degrees C,
      respectively, were achieved in nine chest wall recurrences with intratumoural
      temperature probes. Concurrent hormonal therapy was administered in 48%, and
      concurrent chemotherapy in 10% of patients. RESULTS: Median overall survival time
      was 28 months (Kaplan Meier), with 71% and 54% of patients living 1 and 2 years
      after thermoradiotherapy. The median time to local failure has not been reached,
      local tumour control after 2 years being 53%. Actuarial 1 and 2 year local tumour
      controls for microscopic residual disease were 89%, and for macroscopic nodular
      recurrences 71% and 46%, respectively (p = 0.09). Actuarial 1 and 2 year local
      tumour controls after treatment with a total dose of less than 60 Gy were 51% and
      38%, respectively, and, after a total dose greater than 60 Gy, 84% and 60% (p =
      0.01), respectively. Actuarial 1 year local tumour control was 92% after complete
      tumour remission, versus 57% after partial remission (p = 0.002). Three of the 39
      patients died of cancer en cuirasse, 13 patients due to distant metastases. Acute
      thermoradiotherapy related erythema, dry desquamation and moist desquamation were
      seen in 28.2%, 30.7%, and 30.7% of patients, respectively. Soft tissue necrosis
      occurred in two patients with previous post-operative delayed wound healing, and
      in one patient above a silicon implant. CONCLUSION: This study showed that, in
      extensively pre-treated patients with locally recurrent breast cancer, local
      tumour control after thermoradiotherapy depended on tumour resectability,
      response of macroscopic tumour to thermoradiotherapy, and total irradiation dose.

PMID- 11471982
TI  - Microwave transurethral applicator with helix-loaded-dipole-antenna (HLDA) for
      prostate treatment.
AB  - Three designs of transurethral applicators have been analysed to find the one
      that is best able to selectively heat the desired volume of prostate. A helix
      loaded-dipole-antenna (HLDA) inserted into a Foley type catheter was found to be
      the most promising design. A change in the heat deposition pattern of the antenna
      depending on prostate size is possible by moving the position of the antenna
      within a Foley catheter. A number of prototypes of HLDA were manufactured and
      tested to optimize their design. These tests were performed in solid and liquid
      phantoms and in laboratory animals. Intra-operative measurements of intra
      prostatic temperature distribution were also performed. A comparison of the HLDA
      with other commercially available transurethral applicators and the published
      data showed that the present design has a higher linear homogeneity coefficient
      and a better heat deposition in the prostate.

PMID- 11471983
TI  - Electromagnetic phased arrays for regional hyperthermia: optimal frequency and
      antenna arrangement.
AB  - This paper investigates the effects of the three-dimensional arrangement of
      antennae and frequency on temperature distributions that can be achieved in
      regional hyperthermia using an electromagnetic phased array. It compares the
      results of power-based and temperature-based optimization. Thus, one is able to
      explain the discrepancies between previous studies favouring more antenna rings
      on the one hand and more antennae per ring on the other hand. The sensitivity of
      the results is analysed with respect to changes in amplitudes and phases, as well
      as patient position. This analysis can be used for different purposes. First, it
      provides additional criteria for selecting the optimal frequency. Secondly, it
      can be used for specifying the required phase and amplitude accuracy for a real
      phased array system. Furthermore, it may serve as a basis for technological
      developments in order to reduce both types of sensitivities described above.

PMID- 11471984
TI  - Wild-type p53-function is not required for hyperthermia-enhanced cytotoxicity of
      cisplatin.
AB  - The objective was to test the hypothesis that wild-type p53-function is required
      for the enhancement of the cytotoxicity of cis-diammine-dichloroplatinum(II)
      (cDDP) cytotoxicity by hyperthermia (HT). Human colorectal carcinoma cells (RKO)
      with wild-type p53-function and transfectants with HPV16-E6 or with a dominant
      negative mutant p53 were used. Cells were treated with HT (60 min at 41 degrees
      C, 43 degrees C, 45 degrees C: HT41, HT43, HT45). with various doses of cDDP
      alone or with a combined treatment, simultaneously applied. Survival was
      determined by clonogenic assays. Levels and localization of p53 were analysed
      with immunocytochemistry and Western blotting. The extent of HT41-enhanced
      cytotoxicity of cDDP was similar in all cell lines studied. Immunocytochemistry
      of wild-type p53 cells showed that p53 is transferred to the nucleus within 5 h
      after HT43, whilst after HT41 no significant effects were observed. Cell
      fractionation experiments of wild-type p53 cells showed that, immediately after
      HT43/HT45, nuclear p53-levels increased as compared to controls, but could not be
      extracted from the matrix. The extractability was restored 3-5 h after treatment.
      No significant differences in p53-levels were observed after HT41. These results
      indicate that, although HT43/HT45 might shortly inactivate p53-function, probably
      by protein aggregation to the nuclear matrix, the HT-enhanced cDDP-cytotoxicity
      does not depend on p53-function.

PMID- 11471985
TI  - Effects of the flavonoid drug quercetin on the response of human prostate tumours
      to hyperthermia in vitro and in vivo.
AB  - Tumour hyperthermia, although potentially a powerful therapeutic agent and
      radiation sensitizer, is hindered by a number of considerations including
      inhomogeneous heating of deep seated tumours due to energy deposition and
      perfusion issues. One solution is to design hyperthermia sensitizers to amplify
      the effects of hyperthermia, particularly at cold spots within the tumour
      undergoing treatment. This study examined the use of Quercetin, a flavonoid drug
      shown previously to antagonize the expression of HSP72 and induce apoptosis as a
      sensitizer of prostate cancer growth in vivo. Quercetin dose-dependently
      suppressed PC-3 tumour growth in vitro and in vivo. When combined in a treatment
      protocol with hyperthermia, quercetin drastically inhibited tumour growth and
      potently amplified the effects of hyperthermia on two prostate tumour types, PC-3
      and DU-145 in vivo. These experiments, thus, suggest the use of Quercetin as a
      hyperthermia sensitizer in the treatment of prostate carcinoma.

PMID- 11471986
TI  - Influence of clamping-induced ischemia and reperfusion on the response of a mouse
      melanoma to radiation and hyperthermia.
AB  - PURPOSE: To study the response of a mouse melanoma to radiation and hyperthermia
      under acute hypoxia and reperfusion. MATERIALS AND METHODS: B16F1 melanoma of
      100+/-10 mm3, in C57BL mouse, were locally exposed to 10Gy gamma radiation (RT),
      43 degrees C for 30 min (HT) in a water bath, or RT followed immediately by HT,
      under clamping (acute hypoxia) or 1 h after reperfusion. Tumour regression,
      volume doubling time (VDT), growth delay (GD), apoptosis and microvascular
      density (MVD) were studied. RESULTS: Under clamping, HT increased the VDT and GD
      to > 20 days above control and resulted in > 50% regression (PR) in all the
      tumours, whilst RT + HT synergistically enhanced VDT and GD. Under reperfusion,
      HT produced 25% PR against 16% by RT, with no increase in VDT and GD compared to
      RT. RT + HT significantly enhanced VDT and GD above that of RT or HT, but did not
      further increase PR of reperfused tumours. HT under clamping caused > 50%
      increase in apoptic cells over control and decreased MVD to 1/3rd of control. RT
      + HT further enhanced apoptotic cells to > 70% and reduced MVD to 1/6th of
      control. CONCLUSIONS: These results suggest that combination of radiotherapy with
      hyperthermia could benefit treatment of tumours with ischemia-induced acute
      hypoxia.

PMID- 11471987
TI  - Separation of inosine, hypoxanthine, and guanosine by high-performance liquid
      chromatography on silica.
AB  - The separation of inosine (Ino), hypoxanthine (Hyp), and guanosine (Guo) on
      silica has been studied. In adsorption normal-phase systems the peak shapes are
      unsatisfactory; a low selectivity has been observed for the Ino-Hyp and Guo-Hyp
      pairs. Chromatograms can be significantly improved if systems with a mixed
      partition-adsorption retention mechanism are applied.

PMID- 11471988
TI  - Fatty and resin acid analysis in tall oil products via supercritical fluid
      extraction-supercritical fluid reaction using enzymatic catalysis.
AB  - Supercritical fluid extraction (SFE) is combined with supercritical fluid
      reaction (SFR) in an analytical mode to assess tall oil products for their fatty
      or resin acid content or both. The SFR consists of an inline enzymatically
      catalyzed reaction in which a lipase transesterifies specific lipids with
      methanol. The SFE-SFR sequence is conducted employing commercially available
      extractors using supported lipases in the extraction cell to form methyl esters.
      In this study, six different commercially available lipases are screened for
      activity. The SFE-SFR extracts are analyzed by capillary gas chromatography and
      supercritical fluid chromatography and then compared with tall oil products
      derivatized by conventional chemical derivatization techniques.

PMID- 11471989
TI  - Column robustness case study for a liquid chromatographic method validated in
      compliance with ICH, VICH, and GMP guidelines.
AB  - This article presents a case study in dealing with robustness investigations and
      attempts by our analytical laboratory to address these issues without sacrificing
      valuable time in revamping the method validation prior to submission. A liquid
      chromatographic method is developed for the analysis of a novel triazinetrione
      anticoccidial product. The method effectively separates the active pharmaceutical
      ingredient (API), impurities, and preservatives in the API and product
      formulation. For much of the validation, the method holds up to the rigorous
      guidelines of the International Conference of Harmonization, the International
      Cooperation on Harmonization of Technical Requirements for Registration of
      Veterinary Medicinal Products, and the Good Manufacturing Practices. However, in
      analyzing a base-degraded sample one of the impurity peaks yields inconsistent
      retention times (RTs) during a series of injections. When switching the system to
      another analytical column from the same supplier, this impurity peak elutes at a
      different retention window and the remaining peaks in the chromatographic profile
      remain essentially the same. This RT variation of a single peak in the
      chromatographic profile is observed with additional columns from the same
      supplier and from different manufacturing lots. This suitability problem is not
      encountered with the columns used in the method development stage. The method no
      longer meets the robustness criteria established for pharmaceutical methods. An
      investigation is commenced and it is discovered that with the addition of
      tetrabutylammonium hydroxide to the mobile phases, the impurity peak gives a
      consistent RT in relation to the active peak. The peak shows comparable RTs
      relative to that of the API peak with columns of different silica lots and bond
      lots. All peaks, including the aforementioned impurity peak, are well-resolved
      under the revised high-performance liquid chromatographic conditions. This
      temporary solution enables continued submission work for FDA, but the robustness
      of this method is still a concern. After further investigation, it is determined
      that inhomogeneity of the active sites on the column's stationary phase is the
      likely culprit. Fortunately, a new column is found to be more suitable for this
      method and a column qualification study is initiated.

PMID- 11471990
TI  - Preparation of a ribonucleic acid-(polyamidoamine)-(zirconia-urea-formaldehyde
      resin) high-performance liquid affinity chromatographic stationary phase.
AB  - A preparative method for a high-performance liquid affinity chromatographic
      (HPLAC) stationary phase is described. The 3- to 5-microm nonporous composite
      spherical microparticles of zirconia and urea-formaldehyde (UF) resin are
      synthesized through the reaction of zirconyl chloride with hexamethylene tetra
      amine and urea, and then it is used as the matrix of the HPLAC stationary phase
      of which the diameter and structure are determined by scanning electron
      microscopy. In a methanol medium, the polyamidoamine (PAMAM) starburst dentritic
      spacer arms are linked with the imido-groups on the surface of the matrix by the
      Michael addition reaction with methyl acrylate and the amination reaction with
      ethylene diamine. After repeating these steps in triplets, amine-terminated
      dentritic spacer arms with a generation of 3 are obtained. The topological
      structure of the spacer arms is examined by solid-state 13C NMR. The Br
      substituted ribonucleic acid (RNA) ligand is obtained by the reaction of liquid
      bromine with RNA and bonded to the dendritic spacer arms of the matrix in a
      solution of NaOH (pH 9-11). The binding capacity of RNA is measured by UV
      spectrophotometry. A new type of stationary phase--RNA-(PAMAM)-(zirconia-UF resin
      -for HPLAC, which possesses starburst dendritic spacer arms, is synthesized and
      used for the separation of biological macromolecules.

PMID- 11471991
TI  - High-performance liquid chromatographic determination of pyridostigmine bromide,
      nicotine, and their metabolites in rat plasma and urine.
AB  - This study reports on the development of a rapid and simple method for the
      determination of the antinerve agent drug pyridostigmine bromide (3
      dimethylaminocarbonyloxy-N-methyl pyridinium bromide) (PB), its metabolite N
      methyl-3-hydroxypyridinium bromide, nicotine (S-1-methyl-5-(3-pyridyl)-2
      pyrrolidine), and its metabolites nornicotine (2-(3-pyridyl)pyrrolidine) and
      cotinine (S-1-methyl-5-(3-pyridyl)-2-pyrrolidone) in rat plasma and urine. The
      compounds are extracted and eluted by methanol and acetonitrile using C18 Sep-Pak
      cartridges and separated using high-performance liquid chromatography by a
      gradient of methanol, acetonitrile, and water (pH 3.2) at a flow rate of 0.8
      mL/min in a period of 14 min. UV detection was at 260 nm for nicotine and its
      metabolites and at 280 nm for PB and its metabolite. The limits of detection
      ranged between 20 and 70 ng/mL, and the limits of quantitation were 50-100 ng/mL.
      The average percent recovery of five spiked plasma samples were 85.7 +/- 7.3%,
      80.4 +/- 5.8%, 78.9 +/- 5.4%, 76.7 +/- 6.4%, and 79.7 +/- 5.7% and for urine were
      85.9 +/- 5.9%, 75.5 +/- 6.9%, 82.6 +/- 7.9%, 73.6 +/- 5.9%, and 77.7 +/- 6.3% for
      nicotine, nornicotine, cotinine, PB, and N-methyl-3-hydroxypyridinium bromide,
      respectively. The calibration curves for standard solutions of the compounds of
      peak areas and concentration are linear for a range between 100 and 1,000 ng/mL.
      This method is applied in order to analyze the previously mentioned chemicals and
      metabolites following their oral administration in rats.

PMID- 11471992
TI  - Screening of psychotropic drugs in human hair based on high-performance thin
      layer chromatography and microliquid extraction.
AB  - The monitoring of the physiological and functional state of personnel from
      dangerous industries is very important for the ensuring of ecological security.
      Usually, this involves testing for the consumption of alcohol and drugs of abuse.
      During the last several years the use of legal psychotropic drugs has increased
      and the control over these drugs has became an actual problem. As is well known,
      the long-term history of drugs present in the body is accessible through hair
      analysis. This is why the aim of our research is to create a screening procedure
      based on coupling high-performance thin-layer chromatography with microliquid
      extraction as a psychotropic drug testing method for hair. Some widely
      distributed antidepressants, neuroleptics, and sedative drugs are chosen for
      research. The optimal experimental conditions for all of the consequent steps for
      the screening detection of the model samples are determined. The visual and
      densitometric detection limits allow for the employment of the proposed technique
      for a fast and cost-effective analysis of the drugs of abuse.

PMID- 11471993
TI  - Simple and rapid analysis for quantitation of the most important volatile flavor
      compounds in yogurt by headspace gas chromatography-mass spectrometry.
AB  - The aim of this experiment is to develop a rapid, simplified, direct gas
      chromatographic (GC) method for the analysis of volatile flavor compounds in
      yogurt combining a headspace with constant heating temperature and GC with a mass
      spectrometric detect ion. Repeatability of the method is assessed. The relative
      standard deviation for individual flavor compounds range from 3.5% for
      acetaldehyde to 8.4% for acetone, with a total mean value of 52.4 +/- 2.2 mg/kg
      for all of the studied aroma components. Recovery for individual flavor compounds
      range from 63.7% for acetone to 82.4% for acetic acid.

PMID- 11471995
TI  - Liquid chromatography problem solving and troubleshooting.

PMID- 11471994
TI  - Trace-level determination of benzidine and 3,3'-dichlorobenzidine in aqueous
      environmental samples by online solid-phase extraction and liquid chromatography
      with electrochemical detection.
AB  - A simple, rapid, and reliable online methodology for the determination of
      benzidine and 3,3'-dichlorobenzidine (3,3'-DCB) in natural waters is proposed.
      The analytes are extracted and preconcentrated from aqueous samples in a small
      stainless steel precolumn packed with a polymeric PLRP-S phase. The precolumn is
      further online-analyzed by reversed-phase gradient-elution chromatography with a
      highly sensitive and selective coulometric detection at E = 700 mV. Recoveries
      greater than 90% and a relative standard deviation of approximately 5% are
      achieved with samples spiked at low micrograms-per-liter concentration levels.
      The detection limits of the method in fortified reagent water samples are 100
      ng/L for benzidine and 50 ng/L for 3,3'-DCB.

PMID- 11471996
TI  - Gas chromatography problem solving and troubleshooting.

PMID- 11471997
TI  - Anterior corneal optical aberrations induced by photorefractive keratectomy for
      hyperopia.
AB  - PURPOSE: Photorefractive keratectomy (PRK) for hyperopia requires both a
      steepening of the central cornea and a flattening of the mid-periphery to achieve
      its effect and is likely to affect the optical aberrations of the eye. METHODS:
      Nine patients underwent PRK to correct between +2.00 and +4.00 D of hyperopia
      (first eye treated for each patient) using the Summit Technology Apex Plus
      excimer laser. Anterior corneal aberrations for pupil diameters of 3, 5.5 and 7
      mm were estimated from corneal topography data (TMS-1), assuming a uni-index,
      single surface cornea. Refractive error was assessed using retinoscopy and
      standard subjective tests. RESULTS: Apart from the intended change in refraction
      (mean spherical equivalent manifest refraction, +4.60 +/- 1.60 D before surgery
      and +0.70 +/- 1.60 D at 1 year after surgery), the most significant change was in
      spherical aberration. Anterior corneal spherical aberration was positive (+1.60
      +/- 0.60 D for a 5.5-mm pupil) before surgery and became negative after surgery (
      1.80 +/- 1.20 D at 1 year). The change in spherical aberration was related to the
      achieved change in refractive error. CONCLUSIONS: The large change (approximately
      3.00 D) in spherical aberration (from positive to negative aberration) has
      implications for the optical performance of the whole eye, where the effects of
      lenticular aberration must also be considered.

PMID- 11471998
TI  - Schematic eye models for simulation of patient visual performance.
AB  - PURPOSE: To determine if model eyes can simulate the visual performance of normal
      human eyes under conditions of varying low myopic blur, pupil size, and contrast.
      METHODS: High and low contrast Bailey-Lovie logMAR visual acuity (VA) of three
      normal eyes of three subjects were measured for four artificial pupil sizes and
      ten levels of myopic defocus. Simulated visual acuities were then determined for
      three model eyes--the Indiana Eye with no spherical aberration, the Indiana Eye
      with average spherical aberration, and the Kooijman Eye--by generating optically
      aberrated VA charts for each testing condition using Visual Optics Lab software
      by Sarver and Associates, Inc, and having the subjects read high resolution
      printouts of these charts using a 3-mm pupil and optimal spectacle correction.
      The correlation between real VA and simulated VA was then plotted and a
      regression line calculated. RESULTS: Slopes for the Indiana Eye, Indiana Eye with
      spherical aberration, and Kooijman Eye were 0.98, 0.98, and 1.01 for high
      contrast, and 0.92, 0.67, and 0.75 for low contrast, respectively. The r2 values
      were 0.73, 0.74, and 0.77, for high contrast, and 0.69, 0.40, and 0.50 for low
      contrast, respectively. Under low contrast conditions the Indiana Eye VA was
      significantly closer to the real VA than that of the other two models (P<.0003).
      CONCLUSION: Visual performance can be simulated by eye models. The simple single
      surface Indiana Eye with no spherical aberration best modeled both high and low
      contrast visual acuity.

PMID- 11471999
TI  - Changes in intraocular pressure after laser in situ keratomileusis.
AB  - PURPOSE: To evaluate changes in intraocular pressure (IOP) measurements by
      Goldmann applanation tonometry after laser in situ keratomileusis (LASIK) for
      myopia and myopic astigmatism, and to assess the accuracy of Goldmann applanation
      tonometry measurements after LASIK in these eyes. METHODS: LASIK was performed on
      166 eyes of 93 patients for correction of myopia and myopic astigmatism.
      Intraocular pressure was measured by Goldmann applanation tonometry at the
      central and temporal parts of the cornea before and at 1, 3, 6, and 12 months
      after LASIK. The amount of change in IOP was computed and its relation to
      different variables was evaluated by regression analysis. RESULTS: Intraocular
      pressure measured at the center of the cornea was reduced by a mean of 3.69 +/-
      1.63 mmHg after LASIK. Multiple regression analysis showed that the decrease in
      IOP was related to the preoperative IOP and the change in central corneal
      thickness after LASIK. Measurements of IOP at the temporal part of the cornea
      were also reduced by a mean of 2.39 +/- 1.71 mmHg. There was wide variability in
      the amount of difference between the temporal and central measurements after
      LASIK (temporal measurements were higher than central by 0 to +4 mmHg).
      CONCLUSION: LASIK for myopia produced underestimation of IOP measured by Goldmann
      applanation tonometry at the central part of the cornea by a mean of 3.69 +/-
      1.63 mmHg. The decrease of IOP was related to preoperative IOP and the change in
      central corneal thickness after LASIK. Temporal Goldmann applanation tonometry
      measurements, although decreased after LASIK, were less reliable.

PMID- 11472000
TI  - Morphology of the stromal surface and endothelium using two different
      microkeratomes.
AB  - PURPOSE: To compare stromal surface and endothelial morphology after
      keratectomies and after laser in situ keratomileusis (LASIK), using two different
      microkeratomes. METHODS: Keratectomies (160-microm and 400-microm) were performed
      on 82 enucleated porcine eyes using the Chiron Automated Corneal Shaper (52 eyes)
      and the Microtech Turbokeratome (30 eyes). LASIK procedures of -9.00 D, -27.00 D,
      and -36.00 D were performed with a Schwind excimer laser. The corneas were
      immediately fixed in glutaraldehyde or stained with alizarin red and trypan.
      Scanning electron microscopy was then performed. RESULTS: All keratectomies
      performed with the Chiron microkeratome displayed a relatively smooth surface.
      The quality of the keratectomies with the manually advanced Microtech
      microkeratome was variable, with a high incidence (4 of 9) of incomplete cuts and
      irregular surfaces. In the eyes in which the stromal laser ablation was
      performed, a thin layer of condensed stroma (pseudomembrane formation) was seen.
      Vital staining did not indicate endothelial damage. CONCLUSIONS: The surface
      morphology was unacceptable for one of the microkeratomes tested. Keratectomies
      of 160 to 400 microm and LASIK up to -36.00 D did not acutely alter endothelial
      morphology in porcine eyes.

PMID- 11472001
TI  - Visual rehabilitation with contact lenses after laser in situ keratomileusis.
AB  - PURPOSE: Laser in situ keratomileusis (LASIK) has become the surgical treatment
      of choice for moderate myopia and is in widespread use globally. Visual potential
      is sometimes limited due to irregular corneal topography following surgery.
      METHODS: A retrospective chart review of 35 eyes of 22 patients requiring visual
      rehabilitation following LASIK was performed. Four contact lens designs were used
      and evaluated for appropriate cornea-contact lens fitting relationship. RESULTS:
      Mean best contact lens-corrected visual acuity of 20/25 was significantly better
      than best spectacle-corrected visual acuity of 20/40. The average time from
      surgery to contact lens fitting was 8 months, with almost half (10/22) being
      fitted at 4 months. An aspheric design with 0.17 mm of axial edge lift was used
      most commonly. Lens diameters ranged from 9.2 to 10.9 mm, with a mean diameter of
      10.2 mm. The contact lens base curve to cornea relationship would suggest an
      initial base curve selection to be approximately 2.1 D steeper than the mean
      postoperative keratometric power. CONCLUSIONS: Rigid gas permeable contact lenses
      can improve visual function in patients with irregular corneal topography after
      LASIK.

PMID- 11472002
TI  - Photorefractive keratectomy for astigmatism with the Meditec MEL 60 laser.
AB  - PURPOSE: To evaluate the results of photorefractive keratectomy (PRK) in eyes
      treated with astigmatic refractive errors. METHODS: Nine hundred forty eyes were
      treated with the Aesculap Meditec MEL 60 ArF excimer laser. Treatment groups
      were: Group 1 (n=746) eyes with compound myopic astigmatism, Group 2 (n=104) eyes
      with compound hyperopic astigmatism, Group 3 (n=75) eyes treated for mixed
      astigmatism, and Group 4 (n=15) eyes with simple myopic astigmatism (negative
      cylinder). RESULTS: In Group 1, the preoperative spherical equivalent refraction
      of -6.10 D with an average of -1.50 D cylinder decreased to -0.95 D with -0.13 D
      cylinder; uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 86%
      (642/746 eyes); 20/20 or better in 58% (433/746 eyes); 0.8% (6/746 eyes) lost two
      lines of spectacle-corrected visual acuity (SCVA); 74% (552/746 eyes) were within
      +/-0.50 D and 93% (694/746 eyes) were within +/-1.00 D of target refraction. In
      Group 2, preoperative mean +4.57 D spherical equivalent refraction with an
      average of +1.57 D cylinder decreased to +1.13 D with +0.38 D cylinder; UCVA of
      20/40 or better was achieved in 84% (87/104 eyes); 20/20 or better in 46% (48/104
      eyes); 14,4% (15/104 eyes) lost two or more lines of SCVA; 52% (54/104 eyes) were
      within +/-0.50 D and 82% (85/104 eyes) were within +/-1.00 D of target
      refraction. In Group 3, mean preoperative -4.20 D cylinder and +3.00 D spherical
      equivalent refraction decreased to -0.50 D cylinder and -0.50 D spherical
      equivalent refraction; UCVA of 20/40 or better was achieved in 83% (62/75 eyes);
      20/20 or better in 32% (24/75 eyes); 13.3% (10/75 eyes) lost two or more lines of
      SCVA. In Group 4, mean preoperative -3.98 D cylinder decreased to -0.62 D
      cylinder; UCVA of 20/40 or better was achieved in 60% (9/15 eyes); none of the
      eyes achieved 20/20 or better; SCVA remained stable in 6.6% (1/15 eyes) and
      decreased two or more lines in 20.0% (3/15 eyes); 20% (3/15 eyes) were within +/
      0.50 D and 53.3% (8/15 eyes) were within +/-1.00 D of target refraction.
      CONCLUSION: PRK with the Meditec MEL 60 laser produced the best results in eyes
      with compound myopic astigmatism (Group 1). In all other groups, results were
      less predictable.

PMID- 11472003
TI  - Corneal temperature changes during photorefractive keratectomy using the
      Laserscan 2000 flying spot laser.
AB  - PURPOSE: To evaluate the thermal variations during photorefractive keratectomy
      (PRK) induced by a Laserscan 2000 flying spot excimer laser. METHODS: Thermal
      changes during PRK were recorded using a non-contact infrared thermometer on 58
      eyes with an attempted correction ranging from -1.25 to -9.00 D. The eyes were
      randomly divided into two groups to test the thermal effects of two different
      ablation scan techniques: sequential and randomized modes. Thermal measurements
      were also performed during myopic ablations on polymethylmethacrylate (PMMA) test
      plates. RESULTS: On PMMA plates, a significant relationship between the amount of
      attempted myopic correction and thermal changes was established (P=.017 in
      sequential mode and P=.007 in randomized mode); this was not established for
      human eyes. With the sequential mode, an unexpected cooling effect after PRK was
      reported for each myopia subgroup (P=.003 in the low and high myopia subgroups,
      P<.001 in the medium myopia subgroup). With the randomized mode, the cooling
      effect was detected only for low amounts of myopia. CONCLUSION: Despite a high
      repetition rate, the Laserscan 2000 flying spot laser minimized thermal shock. In
      comparison with randomized (nonsequential) pulse application, sequential pulsing
      showed no increase in the thermal loading of corneas. In fact, a cooling effect
      during PRK was produced.

PMID- 11472004
TI  - Reversal of myopic anisometropic amblyopia with phakic intraocular lens
      implantation.
AB  - PURPOSE: To report a case of reversal of myopic anisometropic amblyopia with
      phakic intraocular lens implantation. METHODS: A 6-year-old boy with
      anisometropic amblyopia with spherical equivalent refraction of right eye: -14.00
      -3.00 x 100 degrees, left eye: -0.50 -3.25 x 90 degrees, was treated for 2 years
      with occlusion to the left eye, with poor results. Refractive surgery was planned
      because of contact lens intolerance at age 8 years. A -15.00-D iris claw Artisan
      intraocular lens (IOL) was implanted. RESULTS: Following surgery, treatment of
      the amblyopia and spectacle correction of -4.00 D cylinder at 85 degrees in the
      right eye and -3.50 D cylinder at 90 degrees in the left eye was necessary.
      Visual acuity 6 months after surgery was 20/25 in the right eye and 20/20 in the
      left eye, and has remained stable 18 months after surgery. CONCLUSION: Myopic
      anisometropic amblyopia in an 8-year-old boy was treated successfully with
      implantation of an Artisan iris claw phakic anterior chamber IOL, combined with
      occlusion therapy, and resulted in reversal of amblyopia.

PMID- 11472005
TI  - Diffuse lamellar keratitis associated with recurrent corneal erosions after laser
      in situ keratomileusis.
AB  - PURPOSE: Diffuse lamellar keratitis (DLK) is marked by the presence of diffuse or
      multifocal infiltrates confined to the laser in situ keratomileusis (LASIK)
      interface. These infiltrates are culture-negative, and the etiology is thought to
      be noninfectious. Most cases of DLK occur within the first week or two following
      surgery. METHODS: We describe one case of diffuse lamellar keratitis that
      occurred 3 months after LASIK. The patient developed a spontaneous corneal
      erosion in one eye. Over the next 2 days while the erosion was being treated,
      there was rapid development of DLK. Slit-lamp biomicroscopy and in vivo scanning
      slit confocal microscopy were performed. The patient was treated with intensive
      topical corticosteroids. RESULTS: Scanning slit confocal microscopy revealed
      numerous, highly-reflective round bodies consistent with a polymorphonuclear
      infiltrate located at the flap interface. Treatment with topical 1.0%
      prednisolone acetate was instituted, with rapid improvement in patient symptoms,
      visual acuity, and slit-lamp biomicroscopy. CONCLUSIONS: Diffuse lamellar
      keratitis may occur months after LASIK as a result of a spontaneous recurrent
      corneal epithelial erosion.

PMID- 11472006
TI  - Reduction of hyperopia associated with manual excision of Salzmann's nodular
      degeneration.
AB  - PURPOSE: Removing central corneal pathology often leads to a hyperopic shift
      secondary to corneal flattening. A myopic shift, or reduction in hyperopia, would
      be expected after removal of peripheral corneal pathology with central corneal
      steepening. This case illustrates the refractive changes induced by Salzmann's
      nodular degeneration and the myopic shift associated with their excision.
      METHODS: A 53-year-old female presented with a slowly progressive increase in
      hyperopia. Vision in the right eye was 20/40 with a refraction of +10.00 -4.00 x
      90 degrees. Vision in the left eye was 20/30 with a refraction of +5.75 -2.00 x
      105 degrees. Both corneas exhibited nodular subepithelial opacities in the mid
      periphery. A superficial keratectomy was performed on each eye, 1 year apart.
      RESULTS: Twelve days postoperatively, uncorrected visual acuity in the right eye
      was 20/25, and 20/20 with a refraction of -0.75 -0.50 x 31 degrees, 6 months
      later. Six days postoperatively, uncorrected visual acuity in the left eye was
      20/40, and 20/30 with a refraction of -1.25 D, 1 month later. CONCLUSION:
      Superficial keratectomy provides a means of restoring the original corneal
      contour, especially when the pathology is easily dissected from Bowman's layer.
      The surgeon should investigate the refractive status prior to the development of
      the nodules and be aware of the possible refractive change upon removal of the
      pathology.

PMID- 11472007
TI  - Transepithelial PTK/PRK over complicated LASIK flaps.

PMID- 11472008
TI  - Standards for reporting results of refractive surgery.

PMID- 11472009
TI  - Standards for reporting results of refractive surgery.

PMID- 11472010
TI  - Can we combine astigmatic keratotomy and multifocal lens implantation?

PMID- 11472011
TI  - Complications of LASIK.

PMID- 11472012
TI  - Structural characteristics of protein binding sites for calcium and lanthanide
      ions.
AB  - Surveys of X-ray structures of Ca2+-containing and lanthanide ion-containing
      proteins and coordination complexes have been performed and structural features
      of the metal binding sites compared. A total of 515 structures of Ca2+-containing
      proteins were considered, although the final data set contained only 44
      structures and 60 Ca2+ binding sites with a total of 323 ligands. Eighteen
      protein structures containing lanthanide ions were considered with a final data
      set containing eight structures and 11 metal binding sites. Structural features
      analysed include coordination numbers of the metal ions, the identity of their
      ligands, the denticity of carboxylate ligands, and the type of secondary
      structure from which the ligands are derived. Three general types of calcium
      binding site were identified in the final data set: class I sites supply the Ca2+
      ligands from a continuous short sequence of amino acids; class II sites have one
      ligand supplied by a part of the amino acid sequence far removed from the main
      binding sequence; and class III sites are created by amino acids remote from one
      another in the sequence. The abundant EF-hand type of Ca2+ binding site was under
      represented in the data set of structures analysed as far as its biological
      distribution is concerned, but was adequately represented for the chemical survey
      undertaken. A turn or loop structure was found to provide the bulk of the ligands
      to Ca2+, but helix and sheet secondary structures are slightly better providers
      of bidentate carboxylate ligation than turn or loop structures. The average
      coordination number for Ca2+ was 6.0, though for EF-hand sites it is 7. The
      average coordination number of a lanthanide ion in an intrinsic protein Ca2+ site
      was 7.2, but for the adventitious sites was only 4.4. A survey of the Cambridge
      Structural Database showed there are small-molecule lanthanide complexes with low
      coordination numbers but it is likely that water molecules, which do not appear
      in the electron density maps, are present for some lanthanide sites in proteins.
      A detailed comparison of the well-defined Ca2+ and lanthanide ion binding sites
      suggests that a reduction of hydrogen bonding associated with the ligating
      residues of the binding sites containing lanthanide ions may be a response to the
      additional positive charge of the lanthanide ion. Major structural differences
      between Ca2+ binding sites with weak and strong binding affinities were not
      obvious, a consequence of long-range electrostatic interactions and metal ion
      induced protein conformational changes modulating affinities.

PMID- 11472013
TI  - Dimethyl propionate ester heme-containing cytochrome b5: structure and stability.
AB  - A derivative of rat microsomal cytochrome b5, obtained by substitution of the
      native heme moiety with protoporphyrin IX dimethyl ester, has been characterized
      by 1H and 15N NMR spectroscopy. Besides the two usual A and B forms, which depend
      on the orientation of the heme in the prostethic group cavity, two other minor
      forms have been detected which presumably indicate different conformations of the
      vinyl side chains. The shifts of the heme methyls, as well as the directions of
      the rhombic axes of the magnetic susceptibility tensor, indicate a small
      difference in the orientation of the imidazole planes of the histidine axial
      ligands. The solution structure was determined by using 1,303 meaningful NOEs and
      241 pseudocontact shifts, the latter being derived from the native reduced
      protein. A family of 40 energy-minimized conformers was obtained with average
      RMSD of 0.56+/-0.09 A and 1.04+/-0.12 A for backbone and heavy atoms,
      respectively, and distance and pseudocontact shift penalty functions of 0.50+/
      0.07 A2 and 0.51+/-0.02 ppm2. The structure shows some changes around the cavity
      and in particular a movement of the 60-70 backbone segment owing to the absence
      of two hydrogen bonds between the Ser64 backbone NH and side-chain OH and the
      carboxylate oxygen of propionate-7, present in the native protein. The analysis
      of the NMR spectra in the presence of unfolding agents indicates that this
      protein is less stable than the native form. The decrease in stability may be the
      result of the loss of the two hydrogen bonds connecting propionate-7 to Ser64 in
      the native protein. The available data on the reduction potential and the
      electron transfer rates are discussed on the basis of the present structural
      data.

PMID- 11472014
TI  - The inactivation of horseradish peroxidase isoenzyme A2 by hydrogen peroxide: an
      example of partial resistance due to the formation of a stable enzyme
      intermediate.
AB  - The inactivation of horseradish peroxidase A2 (HRP-A2) with H2O2 as the sole
      substrate has been studied. In incubation experiments it was found that the fall
      in HRP-A2 activity was non-linearly dependent on H2O2 concentrations and that a
      maximum level of inactivation of approximately 80% (i.e. approximately 20%
      residual activity) was obtained with 2,000 or more equivalents of H2O2. Further
      inactivation was only induced at much higher H2O2 concentrations. Spectral
      changes during incubations of up to 5 days showed the presence of a compound III
      like species whose abundance was correlated to the level of resistance observed.
      Inactivation was pH dependent, the enzyme being much more sensitive under acid
      conditions. A partition ratio (r1 approximately equals 1,140 at pH 6.5) between
      inactivation and catalysis was calculated from the data. The kinetics of
      inactivation followed single exponential time curves and were H2O2 concentration
      dependent. The apparent maximum rate constant of inactivation was
      lambdamax=3.56+/-0.07x10(-4)s(-1) and the H2O2 concentration required to give
      lambdamax/2 was K2=9.94+/-0.52 mM. The relationship lambdamax<ki has been shown
      to apply and thus the rate constant of inactivation has been calculated as
      ki=1.9x10(-3)s(-1). HRP-A2 possessed catalase-like oxygen gas-releasing activity,
      the catalytic constant being k3=2.2 s(-1), and the affinity for H2O2 as K2=23 mM.
      Catalase-like activity was pH dependent and favoured under more basic conditions.
      A mechanistic model has been developed and used to explain the behaviour of HRP
      A2. The model suggests that, in common with HRP-C, mechanism-based (suicide)
      inactivation is being observed but that a fraction of the HRP-A2 is protected
      from inactivation in the form of a modified compound III species.

PMID- 11472015
TI  - Purification and characterization of an iron-nickel hydrogenase from Thermococcus
      celer.
AB  - Thermococcus celer cells contain a single hydrogenase located in the cytoplasm,
      which has been purified to apparent homogeneity using three chromatographic
      steps: Q-Sepharose, DEAE-Fast Flow, and Sephacryl S-200. In vitro assays
      demonstrated that this enzyme was able to catalyze the oxidation as well as the
      evolution of H2. T. celer hydrogenase had an apparent MW of 155,000+/-30,000 by
      gel filtration. When analyzed by SDS polyacrylamide gel electrophoresis a single
      band of 41,000+/-2,000 was detected. Hydrogenase activity was also detected in
      situ in a SDS polyacrylamide gel followed by an activity staining procedure
      revealing a single band corresponding to a protein of apparent Mr 84,000+/-3,000.
      Measurements of iron and acid-labile sulfide in different preparations of T.
      celer hydrogenase gave values ranging from 24 to 30 g-atoms Fe/mole of protein
      and 24 to 36 g-atoms of acid-labile sulfide per mole of protein. Nickel is
      present in 1.9-2.3 atoms per mole of protein. Copper, tungsten, and molybdenum
      were detected in amounts lower than 0.5 g-atoms per mole of protein. T. celer
      hydrogenase was inactive at ambient temperature, exhibited a dramatic increase in
      activity above 70 degrees C, and had an optimal activity above 90 degrees C. This
      enzyme showed no loss of activity after incubation at 80 degrees C for 28 h, but
      lost 50% of its initial activity after incubation at 96 degrees C for 20 h.
      Hydrogenase exhibited a half-life of approximately 25 min in air. However, after
      treating the air-exposed sample with sodium dithionite, more than 95% of the
      original activity was recovered. Copper sulfate, magnesium chloride and nitrite
      were also inactivators of this enzyme.

PMID- 11472016
TI  - Expression, purification and characterization of cytochrome P450 Biol: a novel
      P450 involved in biotin synthesis in Bacillus subtilis.
AB  - The bioI gene has been sub-cloned and over-expressed in Escherichia coli, and the
      protein purified to homogeneity. The protein is a cytochrome P450, as indicated
      by its visible spectrum (low-spin haem iron Soret band at 419 nm) and by the
      characteristic carbon monoxide-induced shift of the Soret band to 448 nm in the
      reduced form. N-terminal amino acid sequencing and mass spectrometry indicate
      that the initiator methionine is removed from cytochrome P450 BioI and that the
      relative molecular mass is 44,732 Da, consistent with that deduced from the gene
      sequence. SDS-PAGE indicates that the protein is homogeneous after column
      chromatography on DE-52 and hydroxyapatite, followed by FPLC on a quaternary
      ammonium ion-exchange column (Q-Sepharose). The purified protein is of mixed spin
      state by both electronic spectroscopy and by electron paramagnetic resonance [g
      values=2.41, 2.24 and 1.97/1.91 (low-spin) and 8.13, 5.92 and 3.47 (high-spin)].
      Magnetic circular dichroism and electron paramagnetic resonance studies indicate
      that P450 BioI has a cysteine-ligated b-type haem iron and the near-IR magnetic
      circular dichroism band suggests strongly that the sixth ligand bound to the haem
      iron is water. Resonance Raman spectroscopy identifies vibrational signals
      typical of cytochrome P450, notably the oxidation state marker v4 at 1,373 cm(-1)
      (indicating ferric P450 haem) and the splitting of the spin-state marker v3 into
      two components (1,503 cm(-1) and 1,488 cm(-1)), indicating cytochrome P450 BioI
      to be a mixture of high- and low-spin forms. Fatty acids were found to bind to
      cytochrome P450 BioI, with myristic acid (Kd=4.18+/-0.26 microM) and
      pentadecanoic acid (Kd=3.58+/-0.54 microM) having highest affinity. The fatty
      acid analogue inhibitor 12-imidazolyldodecanoic acid bound extremely tightly
      (Kd<1 microM), again indicating strong affinity for fatty acid chains in the P450
      active site. Catalytic activity was demonstrated by reconstituting the P450 with
      either a soluble form of human cytochrome P450 reductase, or a Bacillus subtilis
      ferredoxin and E. coli ferredoxin reductase. Substrate hydroxylation at the omega
      terminal position was demonstrated by turnover of the chromophoric fatty acid
      para-nitrophenoxydodecanoic acid, and by separation of product from the reaction
      of P450 BioI with myristic acid.

PMID- 11472017
TI  - Steric control of stereoselective interactions between the platinum(II) complex
      [PtCl2(1,4-diazacycloheptane)] and DNA: comparison with cis-[PtCl2(NH3)2] and
      [PtCl2(ethane-1,2-diamine)] using DNA binding and molecular modeling studies.
AB  - The rate and extent of binding of [PtCl2(hpip)] (hpip=homopiperazine-1,4
      diazacycloheptane) and cis-[PtCl2(NH3)2] to calf thymus DNA was measured using
      atomic absorption spectroscopy and it was found that [PtCl2(hpip)] bound both
      more rapidly and to a greater extent than did cis-[PtCl2(NH3)2]. The binding of
      [PtCl2(hpip)] and [PtCl2(en)] (en=ethane-1,2-diamine) to salmon sperm DNA and to
      synthetic, self-complementary 10-base-pair and 52-base-pair oligonucleotides was
      studied using enzymatic digestion and HPLC analysis of the products.
      [PtCl2(hpip)] forms approximately two-fold fewer GpG and ApG intrastrand adducts
      and concomitantly more monofunctional adducts than does [PtCl2(en)]. In the case
      of [PtCl2(hpip)], two GpG adducts, corresponding to the different orientations of
      the hpip ligand with respect to the DNA, were observed in a 1:3.3 ratio. The
      minor product corresponds to the orientation in which the bulkier propylene chain
      of the hpip ligand is adjacent to, and makes close contacts with, the floor of
      the major groove. When the reaction was repeated with a synthetic oligonucleotide
      decamer duplex, the ratio of the two forms was approximately 1:1.9 and with the
      52-mer duplex it was 1:2.4, revealing an apparent systematic dependence of
      stereoselectivity on nucleotide size. Computer modeling of the two adducts formed
      by [PtCl2(hpip)] and those formed by [PtCl2(en)] and cis-[PtCl2(NH3)2] revealed
      that non-bonded interactions between the hpip ligand and the DNA were probably
      responsible for both the decreased proportion of GpG adducts formed by
      [PtCl2(hpip)] and the stereoselectivity exhibited in the formation of these
      adducts. This is the first case in which the stereoselectivity can be ascribed to
      steric factors alone.

PMID- 11472018
TI  - Kinetic and mechanistic studies of the reactions of nitrogen monoxide and nitrite
      with ferryl myoglobin.
AB  - Nitrogen monoxide (nitric oxide) generated endogenously has a variety of
      different properties. Among others it regulates blood pressure and transmission
      of nerve impulses, and has been shown to exert specific toxic effects, but also,
      paradoxically, to protect against various toxic substances. Recent studies
      suggest that NO* can serve as an antioxidant of the highly oxidizing ferryl
      myoglobin (MbFe(IV)=O), which has been proposed to be at least in part
      responsible for the oxidative damage caused by the reperfusion of ischemic
      tissues. In the present work we have determined the rate constant for the
      reaction between MbFe(IV)=O and NO* [(17.9+/-0.5)x10(6)M(-1)s(-1) at pH 7.5 and
      20 degrees C] and we have shown that this reaction proceeds via the intermediate
      nitrito-metmyoglobin complex MbFe(III)ONO. Our results imply that this reaction
      is very likely to take place in vivo and might indeed represent a detoxifying
      pathway for both MbFe(IV)=O as well as NO*. Moreover, we have found that the rate
      of reaction of MbFe(IV)=O with nitrite is significantly lower (16+/-1 M(-1) s(-1)
      at pH 7.5 and 20 degrees C). Thus, this reaction probably plays a role only when
      NO* has been consumed completely and large concentrations of nitrite are still
      present. In contrast to the protecting role of NO*, the reaction with nitrite
      generates nitrogen dioxide which can contribute to tyrosine nitration. Indeed, we
      have demonstrated that nitrite can nitrate added tyrosine in the presence of
      iron(III) myoglobin and hydrogen peroxide.

PMID- 11472019
TI  - Interaction of cisplatin with methionine- and histidine-containing peptides:
      competition between backbone binding, macrochelation and peptide cleavage.
AB  - The pH- and time-dependent reaction of cis-[PtCl2(NH3)2] with the methionine- and
      histidine-containing peptides H-Gly-Met-OH, H-Gly-Gly-Met-OH, Ac-His-Gly-Met-OH,
      and Ac-His-(Ala)3-Met-OH at 313 K has been investigated by ion-pairing reverse
      phase HPLC and NMR spectroscopy. For equimolar solutions (c=0.8 mM, pH
      approximately equals 3 or 8.8), initial formation of the kinetically favored S
      bound complex is followed by relatively rapid metallation of the neighboring
      methionine amide nitrogen NM to afford a kappa2NM,S six-membered chelate. The
      strong trans effect of the methionine S then favors facile NH3 substitution,
      leading to generation of tridentate complexes such as [Pt(H-Gly-MetH(-1)-OH)
      kappa3NG,NM,S)(NH3)]+ or [Pt(H-Ac-His-GlyH(-1)-MetH(-1)-OH-kappa3NG,NM,S)(NH3)].
      In the case of H-Gly-Gly-Met-OH, this reaction is accompanied by loss of a second
      NH3 ligand in alkaline solution to generate the tetradentate kappa4NG1,NG2,NM,S
      species. In contrast, cleavage of the backbone C(O)-N bond to the second
      metallated amide nitrogen after t>100 h is common to the tridentate complexes of
      the tri- and pentapeptides at pH<5. Although an imidazole-coordinated kappa2N3H,S
      macrochelate is formed throughout the whole range 2.5 < or = pH < or = 10 for Ac
      His-Gly-Met-OH, it slowly decays (t=10-1000 h) to the thermodynamically more
      stable tridentate kappa3NG,NM,S complex. All major final products were separated
      and fully characterized by NMR and MS.

PMID- 11472020
TI  - Isocyanide binding to the copper(I) centers of the catalytic core of
      peptidylglycine monooxygenase (PHMcc).
AB  - Binding of the Cu(I)-specific ligands 2,6-dimethylphenyl isocyanide (DIMPI) and
      isopropyl isocyanide (IPI) to the reduced form of peptidylglycine monooxygenase
      (PHM) is reported. Both ligands bind to the methionine-containing CuM center,
      eliciting FTIR bands at 2,138 and 2,174 cm(-1), respectively, but appear unable
      to coordinate at the histidine-containing CuH center in the wild-type enzyme.
      This chemistry parallels that previously observed for CO binding to the reduced
      PHM catalytic core (PHMcc). However, in contrast to the CO chemistry, peptide
      substrate binding did not induce binding of the isocyanide at CuH. XAS confirmed
      the binding of DIMPI at CuM via the observation of a short Cu-C interaction at
      1.87 A and by the lengthening of the Cu-S(methionine) bond length by 0.06 A.
      Similarly, FTIR studies on DIMPI binding to the M314I and H172A mutant forms of
      reduced PHMcc confirmed the assignment of the 2,138-cm(-1) IR band as a CuM-DIMPI
      complex, but surprisingly also showed DIMPI binding to CuH, as indicated by a
      band at 2,148 cm(-1). An inorganic complex, [Cu(1,2-Me2Im)2(DIMPI)](PF6), was
      synthesized and its crystal structure was determined as a model for the
      interaction of isocyanides with imidazole-containing Cu(I) complexes. Comparison
      of EXAFS data for the protein and model suggests that DIMPI probably binds to CuM
      in a tilted fashion, similar to that of ethyl isocyanide binding to myoglobin.

PMID- 11472021
TI  - Oxidation of bis(terpyridine)cobalt(II) chloride by cytochrome c peroxidase
      compounds I and II.
AB  - The bis(terpyridine)cobalt(II), Co(terpy)2(2+), reduction of cytochrome c
      peroxidase compound I, CcP-I, has been investigated using stopped-flow techniques
      as a function of ionic strength in pH 7.5 buffers at 25 degrees C. Co(terpy)2(2+)
      initially reduces the Trp191 radical site in CcP-I with an apparent second-order
      rate constant, k2, equal to 6.0+/-0.4x10(6) M(-1)s(-1) at 0.01 M ionic strength.
      A pseudo-first-order rate constant of 480 s(-1) was observed for the reduction of
      CcP-I by 79 microM Co(terpy)2(2+) at 0.01 M ionic strength. The one-electron
      reduction of CcP-I produces a second enzyme intermediate, CcP compound II (CcP
      II), which contains an oxyferryl, Fe(IV), heme. Reduction of the Fe(IV) heme in
      CcP-II by Co(terpy)2(2+) shows saturation kinetics with a maximum observed rate
      constant, k3max, of 24+/-2 s(-1) at 0.01 M ionic strength. At low reductant
      concentrations, the apparent second-order rate constant for Co(terpy)2(2+)
      reduction of CcP-II, k3, is 1.2+/-0.5x10(6) M(-1) s-1. All three rate constants
      decrease with increasing ionic strength. At 0.10 M ionic strength, values of k2,
      k3, and k3max decrease to 6.0+/-0.8x10(5) M(-1) s(-1), 1.2+/-0.5x10(5) M(-1) s(
      1), and 11+/-3 s(-1), respectively. Both the product, Co(terpy)2(3+), and
      ferricytochrome c inhibit the rate of Co(terpy)2(2+) reduction of CcP-I and CcP
      II. Gel-filtration studies show that a minimum of two Co(terpy)2(3+) molecules
      bind to the native enzyme in low ionic strength buffers.

PMID- 11472022
TI  - Long-range interactions between the Fe protein binding sites of the MoFe protein
      of nitrogenase.
AB  - We report the properties and reactivity of the catalytically active heterologous
      nitrogenase formed between the Fe protein from Clostridium pasteurianum (Cp2) and
      the MoFe protein from Klebsiella pneumoniae (Kp1). Under turnover conditions, in
      the presence of MgATP, a stable 2:1 (Cp2)2Kp1 electron transfer complex is
      formed, in which the [4Fe-4S]+ centre of Cp2 is protected from chelation by
      alpha,alpha'-bipyridyl. However, the two Fe protein-binding sites on Kp1 are not
      equivalent, since a 1:1 Cp2.Kp1 complex was isolated by gel filtration. The non
      equivalence of the Fe protein binding sites was also indicated by the inhibition
      pattern of Klebsiella nitrogenase by Cp2. The EPR spectrum of the isolated 1:1
      Cp2.Kp1 complex showed an S=1/2 signal characteristic of dithionite-reduced Cp2
      and signals with g values of 4.27, 3.73, 2.01 and 4.32, 3.63, 2.00 characteristic
      of the high- and low-pH forms of the FeMoco centre of Kp1, respectively. The
      unoccupied binding site of Kp1 of the isolated 1:1 Cp2Kp1 complex was shown to be
      catalytically fully functional in combination with Kp2. In contrast to homologous
      nitrogenases, which require MgATP for detectable rates of electron transfer from
      the Fe protein, stopped-flow kinetic studies revealed that electron transfer from
      Cp2 to Kp1 occurred in the absence of MgATP with a rate constant of 0.065 s(-1).
      Subsequently, a slower transient decrease and restoration of absorption in the
      electronic spectrum in the 500-700 nm region was observed. These changes
      corresponded with those in the intensity of the S=3/2 EPR signal of the FeMoco
      centres of Kp1 and were consistent with the transient reduction of the FeMoco
      centre of Kp1 to an EPR-silent form, followed by restoration of the signal at
      longer reaction times. These changes were not associated with catalysis since no
      evolution of H2 was detectable.

PMID- 11472023
TI  - Chlorite dismutase from Ideonella dechloratans.
AB  - Chlorite dismutase has been purified from the chlorate-metabolizing bacterium
      Ideonella dechloratans. The purified enzyme is tetrameric, with a relative
      molecular mass of 25,000 for the subunit, and contains about 0.6 heme/subunit as
      isolated. Its catalytic properties are similar, but not identical, to those found
      for a similar enzyme purified earlier from the bacterium GR-1. The heme group in
      Ideonella chlorite dismutase is readily reduced by dithionite, in contrast to the
      GR-1 enzyme, and redox titration gave a value of -21 mV for the midpoint
      potential at pH 7. The heme group has been characterized by optical and EPR
      spectroscopy. It is high-spin ferric at neutral pH, with spectroscopic properties
      similar to those found for cytochrome c peroxidase. In the alkaline pH range, a
      low-spin compound is formed. A 22-residue N-terminal amino acid sequence has been
      determined and no homologue has been found in the protein sequence databases.

PMID- 11472024
TI  - The trail of chromium(III) in vivo from the blood to the urine: the roles of
      transferrin and chromodulin.
AB  - The chromium-binding oligopeptide chromodulin (also known as low-molecular-weight
      chromium-binding substance) has been shown to activate the tyrosine kinase
      activity of the insulin receptor in response to insulin and has been proposed to
      be part of a novel autoamplification mechanism for insulin signaling. The model
      requires that Cr3+ be moved from the blood to insulin-sensitive tissues in
      response to insulin and subsequently be lost in the urine as chromodulin;
      however, the model has not been tested by in vivo studies. In vivo studies with
      rats have shown that the iron transport protein transferrin serves as the major
      chromic ion transport agent and that this transport is stimulated by insulin. The
      ion is transported to a variety of tissues, while liver and kidneys are the major
      target. In hepatocytes, chromodulin occurs in appreciable levels in the cytosol
      and in the nucleus. Apochromodulin levels appear to be maintained under
      homeostatic control, although the only detectable form of urinary chromium is
      probably chromodulin. Increases in urinary chromium loss in response to insulin
      are reflected by increases in chromodulin, establishing a direct link between
      carbohydrate metabolism and the oligopeptide.

PMID- 11472025
TI  - Interactions of iron bleomycin, phosphate or cyanide, and DNA: sequence-dependent
      conformations and reactions.
AB  - The hypothesis was investigated that axial ligands bound to Fe(III)-bleomycin
      [Fe(III)Blm] are destabilized at specific 5'-guanine-pyrimidine-3' binding sites
      but are stable at nonselective dinucleotides. DNA oligomers and calf-thymus DNA
      were used in reactions with L-Fe(III)Blm, where phosphate and cyanide served as
      examples of large and small ligands (L). Both ligands underwent dissociation when
      L-Fe(III)Blm was bound to d(GGAAGCTTCC)2 (I) but not d(GGAAATTTCCC)2 (II) and at
      large ratios of calf-thymus DNA to drug. Fe(III)Blm is high spin in 20 mM
      phosphate buffer, signifying the presence of a phosphate adduct. In the titration
      of HPO4-Fe(III)Blm with calf-thymus DNA, a large excess of DNA was needed to
      reach the low-spin state, consistent with an equilibrium competition between
      phosphate and DNA for Fe(III)Blm. Equilibrium constants for binding Fe(III)Blm
      and CN-Fe(III)Blm to calf-thymus DNA (6.8x10(5) M(-1) and 5.9x10(4) M(-1),
      respectively, in HEPES buffer at 25 degrees C and pH 7.4) showed that the CN-
      ligand also reduced the affinity of DNA for the drug. The kinetics of
      dissociation of CN- from CN-Fe(III)Blm-DNA were slow and first order in bound
      drug. The reversible nature of these dissociation reactions was shown using 1H
      NMR spectroscopy of Fe(III)Blm-I in the absence and presence of large excesses of
      CN- or phosphate. The results are discussed in terms of a two-state hypothesis
      for the binding of L-Fe(III)Blm to specific and nonspecific dinucleotides. It is
      proposed that steric restrictions at specific sites inhibit binding of these
      ligands.

PMID- 11472026
TI  - Effects of extrinsic imidazole ligation on the molecular and electronic structure
      of cytochrome c.
AB  - Although imidazole ligand binding to cytochrome c is not directly related to its
      physiological function, it has the potential to provide valuable information on
      the molecular and electronic structure of the protein. The solution structure of
      the imidazole adduct of oxidized horse heart cytochrome c (Im-cyt c) has been
      determined through 2D NMR spectroscopy. The Im-cyt c, 8 mM in 1.2 M imidazole
      solution at pH 5.7 and 313 K, provided altogether 2,542 NOEs (1,901 meaningful
      NOEs) and 194 pseudocontact shifts. The 35 conformers of the family show the RMSD
      values to the average structure of 0.063+/-0.007 nm for the backbone and 0.107+/
      0.007 nm for all heavy atoms, respectively. The characterization of Im-cyt c is
      discussed in detail both in terms of structure and electronic properties. The
      replacement of the axial ligand Met80 with the exogenous imidazole ligand induces
      significant conformation changes in both backbone and side chains of the residues
      located in the distal axial ligand regions. The imidazole ligand binds
      essentially parallel to the imidazole of the proximal histidine, the two planes
      forming an angle of 8+/-7 degrees. The electron delocalization on the heme moiety
      and the magnetic susceptibility tensor are consistent with these structural
      features.

PMID- 11472027
TI  - Redox thermodynamics of mutant forms of the rubredoxin from
      Clostridiumpasteurianum: identification of a stable Fe(III)(S-Cys)3(OH) centre in
      the C6S mutant.
AB  - Redox thermodynamic data provide a detailed insight into control of the reduction
      potential E degrees' of the [Fe(S-Cys)4] site in rubredoxin. Mutant forms were
      studied in which specific structural changes were made in both the primary and
      secondary coordination spheres. Those changes have been probed by resonance Raman
      spectroscopy. The decrease of approximately 200 mV in E degrees' observed for the
      [Fe(S-Cys)3(O-Ser)]-/2- couples in the surface ligand mutants C9S and C42S is
      essentially enthalpic in origin and associated with the substitution of ligand
      thiolate by ligand olate. However, the pH dependence of the potentials below
      characteristic pKa(red) approximately equals 7 is an entropic contribution,
      plausibly associated with increased conformational flexibility induced by a
      longer Fe(II)-O(H)-Ser bond in the reduced form. The presence of a second surface
      Ser ligand in the new double mutant protein C9S/C42S affects the enthalpic term
      primarily for pH>pKa(red) > or = 9.3, but for pH<pKa(red) the entropic term again
      becomes significant. The available data for the internal ligand mutant C39S
      appear to follow those for the surface ligand mutants. A longer Fe(III)-O-Ser
      link in the oxidized form is expected from structural considerations and a
      smaller decrease of approximately 100 mV in E degrees' is observed for this
      particular [Fe(S-Cys)3(O-Ser)]/2- couple. The reduced form is particularly
      susceptible to hydrolysis with consequent irreversible electrochemistry, an
      apparent consequence of an even longer Fe(II)-O(H)-Ser bond. The second internal
      ligand mutant C6S exhibits starkly different behaviour. The cause was traced to
      the presence of a Fe(III)(S-Cys)3(OH)- centre in the oxidized form. Resonance
      Raman spectroscopy on 54Fe-, H2 18O- and D2O-enriched samples supports the
      presence of an iron hydroxyl group that donates a hydrogen bond to the OH group
      of the free S6 side chain and/or a cluster of bound water molecules. The
      thermodynamic parameters can then be rationalized in terms of the following
      processes: pH>pKa approximately 9: [Fe(III)(S-Cys)3(OH)]- + e- --> [Fe(II)(S
      Cys)3(OH)]2-. pH<pKa: [Fe(III)(S-Cys)3(OH)]- +H+ e- --> [Fe(II)(S-Cys)3(OH2)]-.

PMID- 11472028
TI  - Relaxometric characterization of human hemalbumin.
AB  - Hemalbumin [i.e., Fe(III)-protoporphyrin IX-human serum albumin; Fe(III)heme-HSA]
      is an important intermediate in the recovery of heme iron following hemolysis.
      Relaxometric data are consistent with the occurrence of a hexacoordinated high
      spin Fe(III) center with no water in the inner coordination sphere. The
      relatively high relaxation enhancement observed for an aqueous solution of
      Fe(III)heme-HSA (r1p=4.8 mM(-1)s(-1) at 20 MHz, pH 7, and 25 C) is ascribed to
      the occurrence of a strong contribution from water molecules in the second
      coordination sphere. Structural analysis of the putative binding region has been
      performed by a Monte Carlo simulated annealing procedure, which allowed us to
      identify His105 and Tyr148 as axial ligands. The role of a tyrosinate as the
      sixth Fe(III)heme ligand is supported by the pH-dependent analysis.
      Interestingly, when Fe(III) is replaced by Mn(III), the occurrence of a fast
      exchanging water molecule at pH values close to neutrality is detected. As the pH
      is increased, the Mn(III) containing system behaves analogously to Fe(III)heme
      HSA. At higher pH, the phenolate ligand is eventually displaced by OH- from both
      Fe(III) and Mn(III) centers. Support for the proposed bonding scheme has been
      gained also from competitive binding assays for the sixth coordination site by
      fluoride, azide, and imidazole ligands.

PMID- 11472029
TI  - Minimally invasive thyroid surgery.
AB  - Endoscopic surgery is often considered to be 'minimally invasive surgery' in the
      light of recent technical developments. Endoscopic neck surgery, including
      thyroid and parathyroid surgery, has developed rapidly over the past 2 years. The
      various techniques of thyroid surgery, including sites of incision and procedures
      for creating adequate working space, are described here. The cosmetic benefits of
      endoscopic versus conventional open surgery were evaluated by questionnaires sent
      to two groups of patients. The lower invasiveness of endoscopic surgery in terms
      of operating time and amount of bleeding is also discussed. Endoscopic surgery
      with a new, totally gasless anterior neck skin lifting method, with which we have
      now had much experience, will be described and its advantages discussed.

PMID- 11472030
TI  - Minimally invasive parathyroid surgery.
AB  - Several minimally invasive procedures have been described over the past 3 years
      for the treatment of sporadic primary hyperparathyroidism (PHPT). These
      techniques (totally endoscopic, video assisted and radio guided) have been
      demonstrated to be feasible and safe, but the surgeon should be well trained to
      obtain the best results with these approaches. Not all patients are eligible for
      minimally invasive procedures. The results are comparable to those of
      conventional surgery with advantages in terms of cosmetic result and reduced post
      operative pain. These procedures should be considered to be a valid option by
      surgeons dealing with patients with primary hyperparathyroidism.

PMID- 11472031
TI  - Minimally invasive adrenal surgery.
AB  - The adrenals can be approached endoscopically using either transperitoneal or
      retroperitoneal access, most surgeons favouring the transperitoneal flank
      approach with the patient in the lateral decubitus position. Endoscopic
      retroperitoneal adrenalectomy can be performed via either a posterior or a
      lateral approach. The main advantage of the retroperitoneal approach in the prone
      position is that it allows bilateral adrenalectomy without repositioning the
      patient. Although technically more demanding, endoscopic adrenalectomy provides
      clear advantages over open procedures for tumours less than 5-6 cm in diameter.
      The small working space provided by the retroperitoneal approach is a contra
      indication for the dissection of tumours over 5-6 cm in diameter. Peritoneal
      adhesions caused by previous abdominal surgery or a large right lobe of the liver
      may contra-indicate transperitoneal access. For small benign tumours, the
      transperitoneal and retroperitoneal routes are safe and effective, and there is
      no clear advantage of one procedure over the other. Invasive adrenal carcinoma is
      an absolute contra-indication for endoscopic adrenalectomy. Whether large (>5-6
      cm) and potentially malignant tumours should be removed laparoscopically remains
      debatable.

PMID- 11472032
TI  - Laparoscopic pancreatic surgery in patients with neuroendocrine tumours:
      indications and limits.
AB  - Laparoscopic pancreatic procedures are still at an evaluation stage with regard
      to their indications and techniques. Between January 1998 and December 2000, 13
      patients with endocrine pancreatic tumours - 11 insulinomas and 2 non-functioning
      tumours-underwent laparoscopic surgery, laparoscopic ultrasonography being used
      in all the patients. Enucleation was performed in five patients. The operative
      time was 2-3 hours. Distal pancreatectomy was performed in six patients with
      insulinomas, and spleen preservation with intact splenic vessels was feasible in
      five. Splenectomy was necessary in one patient for technical reasons.
      Laparoscopic distal pancreatectomy with splenic vessel preservation was performed
      in two patients with a large (6 and 8 cm) non-functioning tumour. The mean
      operative time for all the patients undergoing distal pancreatectomy was 4 hours,
      ranging from 3 to 5 hours. A pancreatic fistula occurred in three patients after
      tumour enucleation and in two patients after distal pancreatectomy; the mean
      hospital stay for all patients was 5 days. Enucleation guided by laparoscopic
      ultrasonography thus allows safe tumour dissection and excision, laparoscopic
      distal pancreatectomy also being feasible and safe. Splenic salvage with splenic
      vessel preservation is technically possible. The laparoscopic approach allows a
      shorter hospital stay and an earlier return to normal activities.

PMID- 11472033
TI  - Molecular influences in thyroid and parathyroid surgery.
AB  - Recent progress in molecular biology and genetics has made a major impact on the
      management of patients with multiple endocrine neoplasia syndromes MEN-1 and MEN
      2. The understanding of the mechanisms involved in inherited thyroid and
      parathyroid tumours also offered valuable answers for other models of neoplasia.
      In addition, parathyroid surgery has witnessed rapid progress, from the cloning
      of the calcium receptor to the development of calcimimetics, a new class of drugs
      that could shift the management of hyperparathyroidism from surgical intervention
      to medical treatment. Laboratory techniques initially designed for research are
      more and more being used for clinical diagnosis. For example, the use of the
      polymerase chain reaction is currently being evaluated in the early diagnosis of
      metastatic thyroid carcinoma by identifying specific gene products in the local
      lymph nodes. This chapter attempts to convince the reader that molecular biology
      is no longer restricted to the laboratory but has an increasing impact on
      clinical decisions to which an endocrine surgeon is exposed.

PMID- 11472035
TI  - Early surgical intervention and strategy in patients with multiple endocrine
      neoplasia type 1.
AB  - Patients with multiple endocrine neoplasia type 1 (MEN-1) are an unusual
      challenge to the endocrine surgeon. Pituitary disease is often treated without
      surgery, but nearly all patients will require parathyroidectomy for parathyroid
      hyperplasia. Subtotal parathyroidectomy can be accomplished with a very low rate
      of permanent hypoparathyroidism and an acceptable rate of recurrent
      hyperparathyroidism. The treatment of pancreaticoduodenal disease is quite
      controversial. Even when associated with the Zollinger-Ellison syndrome, early
      and aggressive surgical treatment should be considered to influence the hormonal
      syndrome as well as to address the malignant potential of both pancreatic and
      duodenal tumours. This includes distal pancreatectomy, enucleation of pancreatic
      head lesions, and duodenotomy with the resection of gastrinomas. Many patients
      may be completely cured of the manifestations of their disease. As MEN-1 is an
      uncommon entity, there are very few prospective, randomized data upon which to
      base surgical judgements.

PMID- 11472036
TI  - Isotopic evaluation and therapy in patients with malignant endocrine disease.
AB  - The contribution of nuclear medicine to the diagnosis and treatment of endocrine
      malignancy is increasing. Advances in molecular biology offer new opportunities
      for tumour targeting via surface receptor recognition and tumour-specific
      metabolic markers. Imaging the biodistribution of these markers allows
      quantitative, in vivo characterization of tumour function. There is growing
      interest in the therapeutic potential of nuclear medicine targeting, substituting
      therapeutic beta-emitting radionuclides for the gamma-emitters used in diagnostic
      imaging. Limited clinical experience supports the rationale of this approach in
      patients with inoperable or disseminated disease and controlled trials are in
      progress. This chapter outlines the place of nuclear medicine techniques in the
      routine management of endocrine malignancy and explores areas for further
      development.

PMID- 11472037
TI  - Pancreatic islet transplantation in the treatment of diabetes mellitus.
AB  - This chapter reviews current developments and future directions in clinical islet
      transplantation. With the recent introduction of glucocorticoid-free
      immunosuppressive therapies and improved methods for islet isolation, the success
      of the procedure has increased substantially. Challenges ahead include progress
      with international multicentre trials, development of single donor protocols,
      progress in clinical tolerance based therapies to lower overall risk of
      immunosuppression, and ultimately finding an alternative source to provide
      effective therapy for more patients with diabetes. Recent advances in stem cell
      biology and xenotransplantation may soon provide this opportunity.

PMID- 11472041
TI  - Prevalence and significance of thrombophilia in peripheral arterial disease.

PMID- 11472042
TI  - Treatment efficacy of intermittent claudication by surgical intervention,
      supervised physical exercise training compared to no treatment in unselected
      randomised patients I: one year results of functional and physiological
      improvements.
AB  - OBJECTIVES: to compare the effect of surgery, exercise and simple observation on
      maximum exercise power in claudicants. DESIGN: prospective, randomised study.
      METHODS: a total of 264 unselected claudicants were randomised to supervised
      exercise training, invasive treatment (open surgical or endovascular procedures)
      or observation. One year treatment outcomes were analysed on an intention to
      treat basis. RESULTS: invasively treated patients showed a significant
      improvement in maximum walking power, stopping distance, post-ischaemic blood
      flow and big toe pressure at one year. Patients randomised to physical exercise
      training or to the control group did not improve in any outcome measure.
      CONCLUSION: invasive treatment increased walking capacity, leg blood pressure and
      flow. Supervised physical exercise training offered no therapeutic advantage
      compared to untreated controls.

PMID- 11472043
TI  - Treatment efficacy of intermittent claudication by invasive therapy, supervised
      physical exercise training compared to no treatment in unselected randomised
      patients II: one-year results of health-related quality of life.
AB  - OBJECTIVE: to compare the effectiveness of invasive therapy, supervised physical
      training and no treatment in terms of health-related quality of life (HRQL) in
      patients with intermittent claudication (IC). DESIGN: a prospective, randomised,
      controlled study. MATERIALS: a total of 253 unselected patients with stable IC
      were sequentially randomised into 3 balanced treatment groups. At 1 year follow
      up data from a battery of generic and disease specific HRQL questionnaires, and
      global indices of quality of life and physical condition were available in 171
      patients. RESULTS: compared with a non-diseased reference group, claudicants were
      substantially limited in daily physical functioning, but little affected
      regarding emotional, cognitive and social functioning, or well-being. Invasive
      therapy yielded significantly greater improvements in some aspects of physical
      functioning and walk-related symptoms than training. Training was not superior to
      invasive therapy on any HRQL dimension and superior to no treatment on only one
      dimension. Treatment effects, however, were generally small-to-moderate and
      levels of physical dysfunction in all groups remained higher than reference
      values. CONCLUSIONS: invasive therapy is more effective than supervised training
      in alleviating illness-specific symptoms and improving certain aspects of
      physical functioning - the primary HRQL domains impacted on by IC and the
      principal goals of its treatment. However, since treatment effect sizes were at
      most moderate and given that untreated claudicants reported at most small
      deterioration in HRQL, the level of evidence supporting invasive therapy is
      modest.

PMID- 11472044
TI  - Lipoprotein (a) level and mortality in patients with critical lower limb
      ischaemia.
AB  - OBJECTIVE: to investigate if serum lipoprotein (a) level is a predictor of
      survival in patients with lower limb atherosclerotic occlusive disease. DESIGN:
      prospective follow up study. METHODS: demographic, biochemical and disease
      variables were collected prospectively in 441 patients with lower limb arterial
      occlusive disease. Survival data were obtained at a mean follow up of 44 months,
      and significant risk factors identified by the life table method and multivariate
      Cox regression analysis. RESULTS: the cumulative survival for all patients at
      three and five years was 79% and 63%. Lipoprotein (a) level was the only
      significant independent biochemical predictor for all deaths and
      cardiorespiratory deaths on multivariate analysis, along with age, diabetes
      mellitus, renal impairment, cardiac diseases and major amputation. An elevated
      Lipoprotein(a) level of >24 mg/dl incurred a 107% and 45% increase in mortality
      at three and five years respectively. The higher mortality associated with
      elevated Lipoprotein (a) was particularly evident in patients with critical
      ischemia, in whom three and five year survival was reduced from 85% to 63% and
      67% to 53% (p=0.0064). In claudicants a survival discrepancy was manifested only
      after five years (73% vs 62%), and the overall association did not reach
      statistic significance (p=0.52). CONCLUSIONS: lipoprotein (a) level is a reliable
      biochemical marker for survival in patients with critical ischemia where
      traditional atherosclerosis risk factors were prevalent.

PMID- 11472045
TI  - PTA and stenting after previous aortoiliac endarterectomy.
AB  - OBJECTIVES: to evaluate the feasibility and long-term results of angioplasty and
      stenting in the treatment of restenosis following aortoiliac endarterectomy.
      MATERIALS AND METHODS: between 1991 and 1999 19 patients underwent angioplasty
      with selective stenting for recurrent stenosis after previous aortoiliac
      endarterectomy. Aortic lesions were treated five times in four patients. At the
      iliac level 28 lesions (25 stenosis and three occlusions) were treated in 16
      patients (one patient had a stenosis at the aortic as well as iliac level). All
      patients were followed clinically and by ultrasound. In the second half of 1999,
      an angiogram or spiral CT-angiography was performed in all patients to determine
      long-term outcome. RESULTS: technical success was obtained in all patients and
      clinical success was achieved in 18 of the 19 patients. Angiographic cumulative
      primary patency for aortoiliac lesions was 96% at 1 year and 76% at 3 years.
      CONCLUSIONS: angioplasty with selective stenting of recurrent aortoiliac disease
      after previous aortoiliac endarterectomy is feasible and safe. Long-term clinical
      and angiographic patency rates are in accordance with results of aortoiliac
      angioplasty in general.

PMID- 11472046
TI  - The impact of factor V mutation on the risk for occlusion in patients undergoing
      peripheral vascular reconstructions.
AB  - OBJECTIVE: to determine the impact of Factor V-Leiden on the patency of
      peripheral vascular reconstructions. DESIGN: prospective, open and consecutive
      study. METHODS: a total of 775 patients, who were electively admitted between
      1995 and 1997 to the vascular ward unit, were prospectively analysed for
      frequency of Factor V-Leiden mutation and patency of reconstruction (one month
      and one year). The patients were grouped into carotid, abdominal aortic aneurysm
      (AAA), renal artery, aortoiliac, infrainguinal, and venous categories according
      to procedures and anatomical sites. Post-reconstruction complications and
      associated risk factors were also analysed. RESULT: in infrainguinal patients
      Factor V-Leiden was seen in 16% of the patients compared with 10% in the
      controls. (Odds ratio 1.60, CI 0.91-2.81). Hypertension, pulmonary disease and
      smoking were more frequent in individuals without Factor V-Leiden. Analysing all
      775 reconstructions, occlusions were more frequent at one month (14% vs 12%)
      (p=0.02) in patients with Factor V-Leiden compared with patients without the
      mutation. Though this trend was also noted few patients having infrainguinal
      reconstructions, the difference was not significant (37% vs 22% (p=0.15) and 46%
      vs 27% (p=0.09) after 1 and 12 months, respectively). CONCLUSION: factor V
      mutation (Factor V-Leiden) was more frequent in patients having occluded vascular
      reconstructions. Further evaluation is needed.

PMID- 11472047
TI  - Cell seeded decellularised allogeneic matrix grafts and biodegradable
      polydioxanone-prostheses compared with arterial autografts in a porcine model.
AB  - BACKGROUND: small diameter vascular grafts are limited by their restricted
      availability, early thrombosis, and requirement for anticoagulants. OBJECTIVE: to
      evaluate different approaches to biocompatible vascular grafts. METHODS: sixteen
      allogeneic acellularised arteries seeded with autologous endothelial cells were
      implanted to replace a segment of the common carotid artery (group I). Other
      animals received polydioxanone prostheses (group II: inner diameter, i.d. 4 mm,
      n=18; group III, i.d. 5 mm, n=20) or arterial autografts (group IV, n=8). Graft
      patency was evaluated by means of ultrasound duplex scanning, angiography and
      histology. RESULTS: patency was 54% (71%), 17% (0%), 50% (50%), and 100% (100%)
      in group I, II, III, and IV after 1 week (4 months), respectively. Significant
      differences (p<0.05) were found for group IV versus all other groups at 1 week,
      as well as for group IV versus groups II and III, for group II versus III, and
      group I versus II at 4 months. CONCLUSION: small diameter vascular grafts can be
      engineered from an acellular allogeneic matrix seeded with autologous cells.
      Patency is superior to polydioxanone prostheses but inferior to the arterial
      autograft.

PMID- 11472048
TI  - Prospective comparison of arm veins and greater saphenous veins as
      infrageniculate bypass grafts.
AB  - OBJECTIVES: to compare arm and saphenous veins for infrageniculate bypass
      grafting. DESIGN: prospective non-randomised study. MATERIALS: two hundred
      patients, of which 197 had ischaemic tissue loss or rest pain. METHODS: two
      hundred and eleven infrageniculate vein bypass procedures using 176 greater
      saphenous veins and 35 arm veins. RESULTS: the cumulative primary graft patency
      rate at 1-month and 2 years was 80% and 61% for saphenous vein and 89% and 42%
      for arm vein. The corresponding rates for secondary patency were 84.5% and 68%,
      and 91% and 57%, respectively. These results corresponded to a relative risk of
      secondary failure of 1.53 (95% CI 0.71, 3.31) for arm vein grafts. In subgroup
      analyses, this estimate was 0.93 and 2.1 for primary vs secondary bypasses and
      0.38 and 2.06 for single-vein vs spliced-vein bypasses. Among arm veins, cephalic
      vein grafts performed better than basilic vein grafts. Early mortality was 14%
      for arm vein and 10% for saphenous vein. CONCLUSION: in the setting of
      infrageniculate bypass grafting, arm vein grafts are not equivalent to greater
      saphenous vein grafts, but contribute importantly to a policy of using autologous
      veins. The possibility of equivalence remains for the arm vein graft that uses a
      cephalic vein or is a primary procedure.

PMID- 11472049
TI  - Long-term results of infrainguinal arterial reconstruction with spliced veins are
      equal to results with non-spliced veins.
AB  - OBJECTIVES: to determine the long term patency of spliced and non-spliced
      infrainguinal vein grafts. METHODS: a prospective registry of all patients
      undergoing infrainguinal arterial reconstruction with autogenous vein material
      was retrospectively interrogated. RESULTS: between October 1988 and August 2000,
      515 infrainguinal arterial reconstructions were performed on 472 patients. A
      total of 429 bypasses were performed with uninterrupted greater saphenous vein,
      86 reconstructions using spliced vein segments. There was no significant
      difference in primary (63% vs 57%) and primary assisted patency (81% vs 81%) of
      limb salvage (88% vs 91%) at 5 years. Limb salvage was not different (88% and 91%
      respectively). CONCLUSION the splicing of vein grafts does not compromise patency
      of limb salvage.

PMID- 11472050
TI  - Patency following successful thrombolysis of occluded vascular grafts.
AB  - AIM: to determine patency after successful lysis of occluded bypass grafts.
      METHODS: data were collected from four centres with a wide experience of
      thrombolysis. Outcome following successful lysis was determined from
      prospectively collected data or case notes. Data from 75 patients, 53 men, were
      analysed. RESULTS: median age at time of lysis was 68 years (range 33-88). Median
      age of graft was 12 months (range 1-120). Patency at 12 months was 33% (95% conf.
      interval: 21-44%). There were no differences in patency depending on whether the
      graft was above or below the inguinal ligament or whether an additional procedure
      eg. percutaneous or vein patch angioplasty was carried out. However in those 48
      cases when lysis was deemed complete, i.e. there was restoration of graft patency
      and at least one vessel run off patency at 12 months was 39% compared with 17% if
      lysis was incomplete (p=0.04). CONCLUSIONS: at the present time it is difficult
      to justify routine thrombolysis of occluded grafts when patency, based on
      intention to treat, is approximately 20% at one year. Following successful graft
      lysis the role of anticoagulation and careful graft surveillance require further
      investigation.

PMID- 11472051
TI  - Blood flow in a pedal bypass combined with a free muscle flap.
AB  - OBJECTIVE: to assess the haemodynamic effect of a free muscle flap on the midterm
      success of a pedal bypass. DESIGN: prospective consecutive study. MATERIALS: a
      pedal bypass (autogenous vein graft) combined with a free muscle flap was
      performed in 13 patients with critical leg ischaemia. The feeding artery of the
      flap was anastomosed end-to-side to the bypass. METHODS: blood flow was measured
      in the bypass before and after transplanting the flap. Doppler was used
      postoperatively to assess the patency. RESULTS: the bypass and flap pedicle were
      patent in 11 cases six months postoperatively. Two grafts were thrombosed and the
      legs amputated. In the successful group the median (range) blood flow in the
      bypass was 50 (10-100) ml/min. It increased (p<0.05) after transplantation to 64
      (20-113) ml/min, being 44 (14-97) ml/min distributed to the foot. Blood flow
      through the flap was 20 (6-37) ml/min. The two failing grafts had a flow of 30
      and 51 ml/min before and 48 and 52 ml/min after transplantation, respectively.
      Blood flow through the flap was 47 ml/min and 36 ml/min, respectively. In the
      failure group the free flap received most of the blood supply through the bypass.
      CONCLUSIONS: a free muscle flap connected to an infrapopliteal bypass increases
      the distal outflow bed and thus decreases the outflow resistance and increases
      graft flow.

PMID- 11472052
TI  - Antibodies against Chlamydia pneumoniae predict the need for elective surgical
      intervention on small abdominal aortic aneurysms.
AB  - OBJECTIVE: to compare the ability of two independent Chlamydia pneumoniae
      antibody tests to predict need for small abdominal aortic aneurysm (AAA) repair.
      PATIENTS AND METHODS: annual scans were offered to 149 screening diagnosed small
      AAA (<5 cm). Serum samples were collected for measuring IgA and IgG-antibodies to
      C. pneumoniae by microimmunofluorescence (MIF) test and the new ELISA
      (Labsystems). RESULTS: a significant concordance was found between MIF and ELISA
      titres with Kappa values of 0.29 for S-IgA and 0.42 for S-IgG. IgG antibodies
      measured by ELISA were most predictive for cases expanding operation
      recommendable sizes with a sensitivity and specificity of 80% and 66%,
      respectively. CONCLUSION: the simpler EIA has a high correlation with the MIF
      test and both were predictive for the natural history of AAA. Chlamydia antibody
      test may be used to identify individuals who might benefit from follow-up and
      anti-chlamydia treatment.

PMID- 11472053
TI  - Juxtarenal aneurysm. Comparative study with infrarenal abdominal aortic aneurysm
      and proposition of a new classification.
AB  - OBJECTIVE: to propose an anatomical classification of juxtarenal aortic aneurysm
      (JRA) that relates to their epidemiology and the result of surgical repair.
      MATERIAL AND METHODS: retrospective study of 53 JRA and 376 infrarenal aortic
      aneurysm (AAA) operated between January 1989 and August 1999. RESULTS:
      perioperative mortality after JRA repair was 19% for type A (interrenal), 13% for
      type B (aneurysm of one or two renal origins) and 4% for type C (no infrarenal
      neck). These differences were not significant. The overall perioperative
      mortality after JRA repair (11%) was significantly higher than mortality of AAA
      (3%p<0.01). Postoperative morbidity after JRA repair was 62% for type A, 75% for
      type B and 33% for type C. Postoperative morbidity after type B repair was
      significantly more frequent than after type C (p<0.001). The overall
      postoperative morbidity (51%) was significantly more frequent than after AAA
      repair (26%p<0.01). Preoperative ischaemic heart disease, aortic clamping above
      the coeliac axis and aortic proximal clamping longer than 30 min were significant
      risk factors for death after JRA repair. Survival by life-table analysis at five
      years after JRA repair and AAA repair were respectively 73%+/-7% and 76%+/-3%.
      CONCLUSION: there is a less favourable outcome after JRA repair as compared to
      AAA repair. The complexity of the surgical procedure requires accurate
      preoperative morphological assessment. The proposed classification of juxtarenal
      aneurysms may be helpful in guiding surgical access.

PMID- 11472054
TI  - An intraaortic solution trial to prevent spinal cord injury in a rabbit model.
AB  - OBJECTIVES: to evaluate the effectiveness of an intraaortic delivered solution on
      preventing spinal cord injury. DESIGN: forty rabbits were allocated into five
      equal groups. MATERIALS AND METHODS: one clamp was placed just distal to the left
      renal artery, and another was placed just above the iliac bifurcation for 40 min.
      Group 1 was not infused (control group). Through a 24G vascular catheter inserted
      into the isolated aortic segment, 20 ml of LR solution at room temperature (Group
      2) 20 ml of LR solution at 3 degrees C (Group 3), and 20 ml of LR solution at 3
      degrees C containing 30 mg/kg of methylprednisolone (Group 4) were infused over 3
      min. In Group 5, 10 mg/kg of vitamins E and C were delivered two days before the
      experiment, and 20 ml of LR solution at 3 degrees C containing 30 mg/kg of
      methylprednisolone, and 10 mg/kg of vitamins E and C was infused at the
      operation. Postoperative spinal cord function was assessed using Tarlov's
      criteria. RESULTS: the neurologic status of Groups 3, 4, and 5 was significantly
      superior to that of Groups 1 and 2. No paraplegia was observed in Groups 4 and 5.
      Spastic paraplegia occurred in all rabbits of Groups 1 and 2, and in 20% of Group
      3. In the electron microscopic evaluation of spinal cord specimens, normal
      histologic structure was observed in Groups 4 and 5, whereas, some derangements
      were observed in all others. CONCLUSIONS: intraaortic infusion of a hypothermic
      blended solution containing methylprednisolone, vitamins C and E provided best
      protection against postischaemic spinal cord dysfunction.

PMID- 11472055
TI  - POSSUM for the prediction of mortality and morbidity in infra-renal abdominal
      aortic aneurysm repair. The Hastings experience.

PMID- 11472056
TI  - Challenging preconceptions in the management of the ischaemic heel.

PMID- 11472057
TI  - Haemostatic devices.

PMID- 11472058
TI  - Ischaemia/reperfusion.

PMID- 11472060
TI  - Fractalkine shares signal sequence with TARC: gene structures and expression
      profiles of two chemokine genes.
AB  - In the process of cloning the gene (Scyd1) encoding the mouse CX3C chemokine
      fractalkine, we identified a novel cDNA that encodes a chimeric molecule termed
      fracTARC. This molecule is a variant form of the mouse CC chemokine, TARC (for
      thymus- and activation-regulated chemokine), bearing the fractalkine signal
      sequence instead of its own. Analysis of the genomic organization of the two
      genes revealed that Scyd1 and Scya17, encoding TARC, are tightly linked on
      chromosome 8 and that fracTARC is generated by alternative splicing of the two
      genes. Among tissues in which Scyd1 mRNA is expressed, fracTARC mRNA is
      selectively expressed in brain and kidney, indicating that fracTARC mRNA is
      generated by tissue-specific alternative splicing under the control of the Scyd1
      promoter. On the other hand, Scya17 and the fracTARC gene are reciprocally
      expressed in thymus, brain, lung, and kidney and are never expressed in the same
      tissue. These expression profiles indicate that tissue specificity of Scya17 is
      precisely regulated by two independent mechanisms, one by transcription from its
      own promoter and the other from the promoter of Scyd1 followed by tissue-specific
      alternative splicing. These data provide evidence for a novel mechanism that
      controls gene expression of two independent genes of the same family. Such a
      mechanism may also operate in other genes that are tightly linked on the same
      chromosome.

PMID- 11472061
TI  - Identification and localization of a new human myotubularin-related protein gene,
      mtmr8, on 8p22-p23.
AB  - Myotubularin and myotubularin-related proteins are dual-specificity phosphatases.
      Several myotubularin-related proteins have been identified in humans and mice.
      The members of the myotubularin protein family are highly conserved, from humans
      to yeast. Mutations in the human myotubularin gene (MTM1) lead to X-linked
      myotubular myopathy. Here we isolate and localize a novel putative myotubularin
      related protein gene (MTMR8) on chromosome 8p22--p23,between the markers D8S550
      and D8S265, by exon-trapping experiments and RT-PCR. Genomic sequencing revealed
      that the gene consists of 10 exons and spans approximately 43 kb. The
      corresponding cDNA is 7081 bp. The open reading frame predicts a protein of 549
      amino acids and a calculated molecular mass of 63 kDa. Like myotubularin-related
      protein-5, MTMR8 has no dual-specificity phosphatase domain. It contains a double
      helical motif similar to the SET interaction domain, which is thought to have a
      role in the control of cell proliferation.

PMID- 11472062
TI  - Genetic and physical delineation of the region overlapping the progressive motor
      neuropathy (pmn) locus on mouse chromosome 13.
AB  - The mouse autosomal recessive mutation progressive motor neuropathy (pmn) results
      in early onset motor neuron disease with rapidly progressing hindlimb paralysis,
      severe muscular wasting, and death at 4--6 weeks of age. pmn is thus considered a
      good animal model for motor neuron diseases and the characterization of the
      causative gene should help in understanding the biological causes of human spinal
      muscular atrophies. Here we report the generation of a physical map based on a
      high-resolution and high-density genetic map encompassing the pmn locus on mouse
      chromosome 13. We have positioned the pmn locus and a cluster of markers
      cosegregating with it within a genetic interval of 0.30 cM, delineated by two
      clusters of markers. We have constructed an approximately 850-kb contig of BACs
      spanning the pmn critical region. This BAC contig contains the breakpoint of
      synteny between mouse chromosome 13 and human 1q and 7p regions and lays the
      foundation for identifying at the molecular level such a breakpoint region. The
      physical and genetic maps provided a support for the identification of five
      transcription units positioned in the nonrecombinant interval, and constitute
      invaluable tools for the identification of other candidate genes for the pmn
      mutation.

PMID- 11472063
TI  - Transcript map of the 8p23 putative tumor suppressor region.
AB  - Cancers of the head and neck, prostate, liver, and bladder exhibit minimal
      regions of deletion within chromosomal band 8p23 that either overlap or map very
      close to one another. We previously refined a minimal region of deletion in
      squamous cell carcinomas to a 112-kb interval within 8p23. There seems to be only
      a single gene within this region that is expressed in normal upper aerodigestive
      tract epithelium. This candidate for the squamous cancer suppressor, CUB and
      sushi multiple domains-1 (CSMD1), extends into the minimal regions of deletions
      defined for the other types of cancer with 8p23 deletions. RT-PCR and EST data
      indicate that CSMD1 is also expressed in those organs,making this gene a
      candidate for a suppressor of multiple types of cancer. Both the sequence of the
      gene and the organization of the protein are highly conserved in the mouse.

PMID- 11472064
TI  - Songbird genomics: analysis of 45 kb upstream of a polymorphic Mhc class II gene
      in red-winged blackbirds (Agelaius phoeniceus).
AB  - Here we present the sequence of a 45 kb cosmid containing a previously
      characterized poly-morphic Mhc class II B gene (Agph-DAB1) from the red-winged
      blackbird (Agelaius phoeniceus). We compared it with a previously sequenced
      cosmid from this species, revealing two regions of 7.5 kb and 13.0 kb that
      averaged greater than 97% similarity to each another, indicating a very recent
      shared duplication. We found 12 retroelements, including two chicken repeat 1
      (CR1) elements, constituting 6.4% of the sequence and indicating a lower
      frequency of retroelements than that found in mammalian genomic DNA. Agph-DAB3, a
      new class II B gene discovered in the cosmid, showed a low rate of polymorphism
      and may be functional. In addition, we found a Mhc class II B gene fragment and
      three genes likely to be functional (encoding activin receptor type II, a zinc
      finger, and a putative gamma-filamin). Phylogenetic analysis of exon 2 alleles of
      all three known blackbird Mhc genes indicated strong clustering of alleles by
      locus, implying that large amounts of interlocus gene conversion have not
      occurred since these genes have been diverging. Despite this, interspecific
      comparisons indicate that all three blackbird Mhc genes diverged from one another
      less than 35 million years ago and are subject to concerted evolution in the long
      term. Comparison of blackbird and chicken Mhc promoter regions revealed songbird
      promoter elements for the first time. The high gene density of this cosmid
      confirms similar findings for the chicken Mhc, but the segment duplications and
      diversity of retroelements resembles mammalian sequences.

PMID- 11472065
TI  - Quantitative genetic study of maximal electroshock seizure threshold in mice:
      evidence for a major seizure susceptibility locus on distal chromosome 1.
AB  - We conducted a quantitative trait locus (QTL) mapping study to dissect the
      multifactorial nature of maximal electroshock seizure threshold (MEST) in C57BL/6
      (B6) and DBA/2 (D2) mice. MEST determination involved a standard paradigm in
      which 8- to 12-week-old mice received one shock per day with a daily incremental
      increase in electrical current until a maximal seizure (tonic hindlimb extension)
      was induced. Mean MEST values in parental strains were separated by over five
      standard deviation units, with D2 mice showing lower values than B6 mice. The
      distribution of MEST values in B6xD2 F2 intercrossed mice spanned the entire
      phenotypic range defined by parental strains. Statistical mapping yielded
      significant evidence for QTLs on chromosomes 1, 2, 5, and 15, which together
      explained over 60% of the phenotypic variance in the model. The chromosome 1 QTL
      represents a locus of major effect, accounting for about one-third of the genetic
      variance. Experiments involving a congenic strain (B6.D2-Mtv7(a)/Ty) enabled more
      precise mapping of the chromosome 1 QTL and indicate that it lies in the genetic
      interval between markers D1Mit145 and D1Mit17. These results support the
      hypothesis that the distal portion of chromosome 1 harbors a gene(s) that has a
      fundamental role in regulating seizure susceptibility.

PMID- 11472066
TI  - The MGEA6 multigene family has an active locus on 14q and at least nine
      pseudogenes on different chromosomes.
AB  - The meningioma expressed antigen-6 (MGEA6) was originally identified as an
      immunogenic antigen in meningioma patients. Somatic hybrid panel mapping and
      fluorescence in situ hybridization revealed MGEA6-related sequences on different
      human chromosomes. Here we carry out database analysis to investigate the
      complexity of the MGEA6-related sequences and demonstrate the existence of a
      multigene family. We localized the active gene (spanning over 83 kb) to
      chromosome 14q and elucidated its exon/intron structure. We identified and
      characterized 9 processed pseudogenes on 9 different chromosomes including
      chromosomes 2, 3, 6, 7, 9, 10, 12, 13, and 18. We performed phylogenetic analysis
      and concluded that the MGEA6 pseudogenes may result from more than one
      retrotransposition event; we calculated divergence times of the pseudogenes to be
      between 21.5 and 28.9 million years ago.

PMID- 11472067
TI  - The myosin light chain kinase gene is not duplicated in mouse: partial structure
      and chromosomal localization of Mylk.
AB  - The gene encoding myosin light chain kinase (MYLK) is duplicated on human
      chromosome 3 (HSA3; 3p13;3q21) and on a chromosome with conserved synteny to HSA3
      in most non-human primate species. In human, the functional copy resides on 3q21,
      whereas the 3p13 site contains a pseudogene. To trace the origin of the
      duplication, we characterized the mouse gene Mylk. A single sequence
      corresponding to the functional Mylk was detected. We sequenced a 180-kb
      bacterial artificial chromosome clone containing the 24 first exons of Mylk; the
      complete mouse gene is expected to span >200 kb. Comparisons with the draft of
      the human genome revealed that the sequence and structure of MYLK are conserved
      in mammals. Fluorescence in situ hybridization (FISH) analysis indicated that the
      mouse gene localizes to a single site on chromosome 16B4-B5, a region with
      conserved synteny with HSA3q. Our study provides information on both the
      structure and the evolution of MYLK in mammals and suggests that it was
      duplicated after the divergence of rodents and primates.

PMID- 11472068
TI  - A high-resolution consensus linkage map of the rat, integrating radiation hybrid
      and genetic maps.
AB  - We have constructed a high-resolution consensus genetic map of the rat in a
      single large intercross, which integrates 747 framework markers and 687 positions
      of our whole-genome radiation hybrid (RH) map of the rat. We selected 136 new
      gene markers from the GenBank database and assigned them either genetically or
      physically to rat chromosomes to evaluate the accuracy of the integrated linkage
      RH maps in the localization of new markers and to enrich existing comparative
      mapping data. These markers and 631 D-Got- markers, which are physically mapped
      but still uncharacterized for evidence of polymorphism, were tested for allele
      variations in a panel of 16 rat strains commonly used in genetic studies. The
      consensus linkage map constructed in the GK x BN cross now comprises 1620 markers
      of various origins, defining 840 resolved genetic positions with an average
      spacing of 2.2 cM between adjacent loci, and includes 407 gene markers. This
      whole-genome genetic map will contribute to the advancement of genetic studies in
      the rat by incorporating gene/EST maps, physical mapping information, and
      sequence data generated in rat and other mammalian species into genetic intervals
      harboring disease susceptibility loci identified in rat models of human genetic
      disorders.

PMID- 11472069
TI  - Cloning of tissue-specific genes using serial analysis of gene expression and a
      novel computational substraction approach.
AB  - A paradigm of molecular medicine is the identification of functionally
      specialized genes in the search of defects responsible for human disease. To
      identify novel genes relevant for thyroid physiology, we applied serial analysis
      of gene expression (SAGE) and identified 4260 tag sequences that did not match
      any known gene present in the GenBank database ("no-match" tags). These no-match
      tags represent still uncharacterized transcripts. Most of them are expected to
      correspond to housekeeping genes and only a few to genes with a tissue-restricted
      pattern of expression. To pinpoint the best candidates for tissue-specificity in
      a large series of tags, we used a computer-based approach. We compared the
      relative abundance of 80 no match tags in our thyroid SAGE library with the
      expression level in 14 other SAGE libraries derived from 9 different human
      tissues. Based on the expression data, we developed the "tissue preferential
      expression" (TPE) algorithm to discriminate tags expressed specifically in the
      thyroid. We then selected four tags as preferentially expressed in thyroid.
      Results were validated by RT-PCR and northern blot on multiple-tissue RNA
      samples. Finally, the screening of a thyroid cDNA library with expressed sequence
      tag (EST) sequences related to the selected tags allowed the isolation of four
      novel thyroid-specific cDNAs. We demonstrate that the computational substraction
      of SAGE tags by the proposed TPE algorithm is a rapid and reliable way to
      expedite the cloning of tissue-specific genes through the combined use of SAGE
      and EST databases.

PMID- 11472070
TI  - CLAN, a novel human CED-4-like gene.
AB  - Proteins governing cell death form the basis of many normal processes and
      contribute to the pathogenesis of many diseases when dysregulated. Here we report
      the cloning of a novel human CED-4-like gene, CLAN, and several of its
      alternatively spliced isoforms. These caspase-associated recruitment domain
      (CARD)-containing proteins are expressed at varying degrees in normal human
      tissues and may contribute to a number of intracellular processes including
      apoptosis, cytokine processing, and NF-kappa B activation. The CARD of the CLAN
      proteins binds a number of other CARD-containing proteins including caspase-1,
      BCL10, NOD2, and NAC. Once their physiologic functions are uncovered, CLAN
      proteins may prove to be valuable therapeutic targets.

PMID- 11472071
TI  - Safety aspects of growth hormone replacement in adults.

PMID- 11472072
TI  - Treatment guidelines for acromegaly. Report from a Scandinavian workshop: first
      Scandinavian Workshop on the Treatment of Acromegaly.

PMID- 11472073
TI  - The influence of muscle action on the acute growth hormone response to resistance
      exercise and short-term detraining.
AB  - The effects of resistance training with concentric or concentric-eccentric muscle
      actions on the acute hormonal response to a resistance exercise protocol was
      investigated. Thirty-two men completed a 19 week lower-body resistance training
      program (consisting of the leg press and leg extension exercises) in which they
      (1) performed concentric actions only (CON); (2) performed both concentric and
      eccentric actions (CON-ECC); (3) performed double concentric actions for each
      repetition (CON-CON); or (4) did not exercise. Following training each subject
      performed two exercise tests consisting of three sets of 30 isokinetic concentric
      (day 1) and eccentric (day 2) knee extensions separated by 48 h. The exercise
      tests were repeated following 4 weeks of detraining. Blood samples were obtained
      before and after each exercise test. Serum growth hormone (GH) was significantly
      (P< 0.05) greater for the concentric test in groups CON and CON-CON whereas GH
      was lower for the concentric test in CON-ECC compared with the eccentric test
      prior to detraining. Following detraining, GH was greater during the concentric
      test in CON-ECC than in the eccentric test, whereas no differences were observed
      between the concentric and eccentric tests in CON and CON-CON and the acute GH
      response to resistance exercise was attenuated. These data indicate that GH is
      sensitive to muscle action type with differential responses observed with
      resistance exercise after short-term detraining.

PMID- 11472074
TI  - Growth hormone and insulin-like growth factor-I: effects on the growth of glioma
      cell lines.
AB  - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are known to be
      mitogens for many types of neoplasms. To investigate their role in tumors of
      glial origin, in vitro and in vivo experiments were performed with a panel of
      immortalized glioma cell lines (D54, SNB-19, U87, U251 and U373). Initial
      analysis for mRNA expression demonstrated the following: GH receptor (5/5 cell
      lines positive), IGF-I (0/5), IGF-II (0/5), IGF-I receptor (5/5), IGF-II receptor
      (2/5). Thus, each cell line expressed the necessary receptors to respond to GH
      and the IGFs but there was no autocrine IGF production by the tumors themselves.
      IGF-I stimulated mitogenesis as measured by [(3)H]thymidine uptake experiments in
      U251 and U373 cells. However, when these two IGF-responsive cell lines were
      xenografted into mice, tumor development and growth rates were not significantly
      different in GH-deficient animals (despite having IGF-I serum concentrations only
      31% of normal). Because our studies were performed in immunocompromised animals,
      GH or IGF effects on immune surveillance, known to be important from some
      syngeneic glioma models, would not be likely to contribute to our findings.
      Nevertheless, these studies are important because they demonstrate that the
      growth of glioma cell lines in an in vivo environment can remain robust in a
      GH/IGF-I-deficient setting, even if in vitro experiments indicate that IGF-I is
      mitogenic.

PMID- 11472075
TI  - Insulin-like growth factor-I (IGF-I) analogue, LR(3)IGF-I, ameliorates the loss
      of body weight but not of skeletal muscle during food restriction.
AB  - Insulin-like growth factor-I (IGF-I) is known to have anabolic effects in freely
      fed rats. We have investigated the ability of infused LR(3)IGF-I, an analogue of
      IGF-I, to attenuate the loss of lean tissue due to food restriction in young (5
      weeks) and adult (12 weeks) rats. Groups of rats received food at 100%, 78%, 56%
      or 33% of ad libitum levels. Within each nutrition group the rats were
      continuously infused with LR(3)IGF-I at (98 nmol/day)/kg body weight or vehicle
      for 7 days. At each level of food intake, rats infused with LR(3)IGF-I maintained
      higher body weight (around 3-8%;P< 0.001) and nitrogen retention (P< 0.001) than
      those infused with vehicle alone but muscle protein was not conserved. LR(3)IGF-I
      infusion increased fat loss only in young rats (P< 0.05) despite a reduction in
      plasma insulin levels in both age groups (P< 0.01). Muscle protein turnover rates
      were unaffected by LR(3)IGF-I in young rats. In adult rats LR(3)IGF-I exacerbated
      the effects of food restriction through increased rates of protein breakdown,
      reduced RNA content and reduced rates of protein synthesis (P< 0.05) despite
      their larger fat reserves. Although young and adult rats show differing metabolic
      responses, we conclude that infusion of LR(3)IGF-I to either group during short
      term food restriction does not ameliorate the loss of lean tissue by allowing
      more efficient utilization and/or partitioning of nutrients.

PMID- 11472076
TI  - The growth hormone (GH)-insulin-like growth factor axis during testosterone
      replacement therapy in GH-treated hypopituitary males.
AB  - Several studies suggest a direct effect of sex steroids on insulin-like growth
      factor-I (IGF-I) production. Oestrogen has been hypothesized directly to inhibit
      hepatic IGF-I production, but the role of androgens is not clarified. We aimed to
      investigate whether testosterone exerts a pituitary-independent effect on IGF-I
      and related parameters. Eight adult hypopituitary men (39.9 +/- 5.7 years)
      receiving growth hormone (GH) and testosterone replacement therapy (250 mg
      testosterone enantate every fourth week) participated in this prospective study.
      Frequent blood samples were drawn over a 5 week period in relation to two
      testosterone injections. Mean baseline IGF-I levels were 352 +/- 135 microg/L,
      and they remained unaltered during the study period (analysis of variance
      (ANOVA), P = 0.88). Free IGF-I levels did not change either (ANOVA, P = 0.35).
      Serum IGF binding protein-3 (IGFBP-3) and acid-labile subunit decreased (ANOVA, P
      = 0.04 and P = 0.02 respectively) but post hoc analysis did not reveal a
      particular difference between days. IGFBP-1 increased following testosterone
      administration (ANOVA, P = 0.05), whereas GH binding protein levels tended to
      decrease following testosterone administration (ANOVA, P = 0.08). Prostate
      specific antigen tended slightly to increase after each testosterone injection
      (ANOVA, P = 0.08, post hoc, NS). We conclude that major changes in total IGF-I
      are not induced during conventional intramuscular testosterone replacement in GH
      treated hypopituitary males, suggesting that testosterone effects on IGF-I are
      likely to be secondary to a stimulation of endogenous GH release.

PMID- 11472077
TI  - Diabetogenic activity of 20 kDa human growth hormone (20K-hGH) and 22K-hGH in
      rats.
AB  - To compare the diabetogenic activity of 20 kDa human growth hormone (20K-hGH)
      with that of 22K-hGH, we evaluated insulin sensitivity with a euglycaemic clamp
      in rats. The glucose infusion rate (GIR) in euglycaemic clamp studies was
      measured as an indicator of insulin sensitivity. [(14)C]glucose and 2-[(3)H]
      deoxy- D -glucose injection were used to calculate the rate of glucose
      utilization (R(d)), the hepatic glucose output (HGO), and the glucose metabolic
      index (R(g)'). Both 20K- and 22K-hGH were infused at equivalent rates (1.0
      (mg/kg)/day). A 24 h infusion of 20K-hGH had no significant effects on the GIR,
      R(d), HGO and R(g)(')except for in gastrocnemius muscle. In contrast, 22K-hGH
      significantly lowered the GIR compared with the control (P< 0.001) and 20K-hGH
      groups (P< 0.01). The infusion of 22K-hGH also reduced R(d)compared with the
      controls and the 20K-hGH rats by 46.6% (P< 0.001) and 39.6% (P< 0.05)
      respectively, while no differences were observed in the HGO. Moreover, 22K-hGH
      inhibited glucose uptake, which was estimated from the insulin-stimulated R(g)'
      in some tissues. These results suggest that 22K-hGH inhibits the uptake and use
      of glucose in various tissues, which then leads to insulin resistance. In
      conclusion, the diabetogenicity of 20K-hGH is much weaker than that of 22K-hGH,
      and the reduced insulin-antagonizing action of 20K-hGH could have important
      clinical benefits.

PMID- 11472078
TI  - Determination of free insulin-like growth factor-I in human serum: comparison of
      ultrafiltration and direct immunoradiometric assay.
AB  - Two fundamentally different methods are currently used for the determination of
      free insulin-like growth factor-I (IGF-I): ultrafiltration by centrifugation (UF)
      and direct immunoradiometric assay (IRMA). The aim was to evaluate a commercial
      IRMA (DSL, Webster, TX, USA) and to compare it with UF. In the IRMA it is
      recommended that samples be incubated for 2 h at 5;C. When comparing samples (n =
      8) incubated for 1 and 2 h, levels increased by 27 +/- 5% (P< 0.0001). When
      incubating samples at 22;C instead of 5;C, levels increased by 192 +/- 32% (P<
      0.0001). Addition of IGF-binding protein-1 (IGFBP-1) to normal sera (n = 6) dose
      dependently decreased ultrafiltered free IGF-I only (P< 0.0007). Similarly, UF
      was more sensitive than IRMA to addition of IGFBP-2 (P< 0.05). In healthy
      subjects (n = 35) IRMA yielded 20% higher levels than UF (1.09 +/- 0.09 vs 0.91
      +/- 0.12 microg/L; P< 0.0001). IRMA and UF yielded similar results in healthy
      subjects treated with IGF-I (n = 5) or growth hormone (n = 7) and in acromegalic
      patients (n = 6) before and after somatostatin analogue treatment. However,
      marked differences were observed in conditions with elevated IGFBP-1 and -2. In
      type-1 diabetics (n = 23) ultrafiltered free IGF-I was more reduced than IRMA
      free IGF-I (38 +/- 9 vs 76 +/- 7% of matched controls (n = 13); P< 0.0001). In
      patients with chronic renal failure (n = 25), IRMA free IGF-I was identical to
      control levels (n = 13), whereas ultrafiltered free IGF-I was decreased by 51 +/-
      7% (P< 0.0001). Similarly, women with anorexia nervosa (n = 9) studied before and
      after weight gain showed significant changes in ultrafiltered free IGF-I only (P<
      0.03). In conclusion, IRMA was not very robust with respect to variations in
      sample incubation and this may bias results. IRMA generally yielded higher levels
      than UF, in accordance with the knowledge that IRMA measures free plus readily
      dissociable IGF-I. IRMA was less affected than UF by added IGFBP-1 and -2, and
      reductions in free IGF-I were better revealed by UF than IRMA.

PMID- 11472079
TI  - Age- and gender-related growth hormone responses to intravenous clonidine in
      healthy adults.
AB  - The alpha(2)-adrenoceptor agonist clonidine stimulates growth hormone (GH)
      release in both animals and humans. It has been used to test for GH deficiency in
      children, to assess central alpha(2)-adrenoceptor function in adults and to
      determine the pathophysiological basis and to confirm diagnosis in neurological
      diseases with autonomic failure. The dose and mode of administration, however,
      may be important, as in some studies in adults oral clonidine has minimal effects
      on GH. We report our experience following intravenous (i.v.) clonidine (2
      microg/kg) in 98 normal adults on the neuroendocrine (GH, insulin, glucose and
      catecholamine) and cardiovascular (blood pressure) responses. In males between 25
      and 89 years and females between 25 and 64 years there was a significant rise in
      GH secretion (P < 0.05) after clonidine. Males showed an age-sensitive secretory
      pattern, with the greatest response between 25 and 35 years (P < 0.02). Younger
      males (< 45 years) had significantly higher peak GH levels post-clonidine than
      younger females < 45 years (P < 0.03). No sex-related change was observed in
      older subjects (< 45 years). Clonidine caused a significant fall in plasma
      noradrenalin and adrenalin in all age-sex groups (P< 0.001). There were no
      significant changes in glucose or insulin. There were no effects of age on the
      fall in blood pressure induced by clonidine. In conclusion, i.v. clonidine
      stimulated GH in all age groups and there was a marked sexually dimorphic pattern
      in adults < 45 years. The results overall suggest that i.v. clonidine-GH testing
      provides a reliable method for investigation of central alpha(2)-adrenergic
      function in adult humans.

PMID- 11472081
TI  - Review: automatic particle detection in electron microscopy.
AB  - Advances in cryoEM and single-particle reconstruction have led to results at
      increasingly high resolutions. However, to sustain continuing improvements in
      resolution it will be necessary to increase the number of particles included in
      performing the reconstructions. Manual selection of particles, even when assisted
      by computer preselection, is a bottleneck that will become significant as single
      particle reconstructions are scaled up to achieve near-atomic resolutions. This
      review describes various approaches that have been developed to address the
      problem of automatic particle selection. The principal conclusions that have been
      drawn from the results so far are: (1) cross-correlation with a reference image
      ("matched filtering") is an effective way to identify candidate particles, but it
      is inherently unable to avoid also selecting false particles; (2) false positives
      can be eliminated efficiently on the basis of estimates of particle size,
      density, and texture; (3) successful application of edge detection (or
      contouring) to particle identification may require improvements over currently
      available methods; and (4) neural network techniques, while computationally
      expensive, must also be investigated as a technology for eliminating false
      particles.

PMID- 11472082
TI  - Automated image acquisition for single-particle reconstruction using p97 as the
      biological sample.
AB  - We have used Leginon, a fully automatic system capable of acquiring cryo-electron
      micrographs, to collect data of single particles, specifically of the AAA ATPase
      p97. The images were acquired under low-dose conditions and required no operator
      intervention other than the initial setup and periodic refilling of the cold
      stage dewar. Each image was acquired at two different defocus values. Two
      dimensional projection maps of p97 were calculated from these data and compared
      to results previously obtained using the conventional manual data collection
      methods to film. The results demonstrate that Leginon performs as well as an
      experienced microscopist for the acquisition of single-particle data. The general
      advantages of automation are discussed.

PMID- 11472083
TI  - The effect of overabundant projection directions on 3D reconstruction algorithms.
AB  - The experimental process of collecting images from macromolecules in an electron
      microscope is such that it does not allow for prior specification of the angular
      distribution of the projection images. As a consequence, an uneven distribution
      of projection directions may occur. Concerns have been raised recently about the
      behavior of 3D reconstruction algorithms for the case of unevenly distributed
      projections. It has been illustrated on experimental data that in the case of a
      heavily uneven distribution of projection directions some algorithms tend to
      elongate the reconstructed volumes along the overloaded direction so much as to
      make a quantitative biological analysis impossible. In answer to these concerns
      we have developed a strategy for quantitative comparison and optimization of 3D
      reconstruction algorithms. We apply this strategy to quantitatively analyze
      algebraic reconstruction techniques (ART) with blobs, simultaneous iterative
      reconstruction techniques (SIRT) with voxels, and weighted backprojection (WBP).
      We show that the elongation artifacts that had been previously reported can be
      strongly reduced. With our specific choices for the free parameters of the three
      algorithms, WBP reconstructions tend to be inferior to those obtained with either
      SIRT or ART and the results obtained with ART are comparable to those with SIRT,
      but at a very small fraction of the computational cost of SIRT.

PMID- 11472084
TI  - Spherical reconstruction: a method for structure determination of membrane
      proteins from cryo-EM images.
AB  - We propose a new method for single-particle reconstruction, which should be
      generally applicable to structure determination for membrane proteins. After
      reconstitution into a small spherical vesicle, a membrane protein takes a
      particular orientation relative to the membrane normal, and its position in the
      projected image of the vesicle directly defines two of its three Euler angles of
      orientation. The spherical constraint imposed by the vesicle effectively reduces
      the dimensionality of the alignment search from 5 to 3 and simplifies the
      detection of the particle. Projection images of particles in vesicles
      collectively take all possible orientations and therefore cover the whole Fourier
      space. Analysis of images of vesicles in ice showed that the vesicle density is
      well described by a simple model for membrane electron scattering density. In
      fitting this model we found that osmotically swollen vesicles remain nearly
      spherical through the freezing process. These results satisfy the basic
      experimental requirements for spherical reconstruction. A computer simulation of
      particles in vesicles showed that this method provides good estimates of the two
      Euler angles and thus may improve single-particle reconstruction and extend it to
      smaller membrane proteins.

PMID- 11472085
TI  - An ab initio algorithm for low-resolution 3-D reconstructions from cryoelectron
      microscopy images.
AB  - A statistical method for determining low-resolution 3-D reconstructions of virus
      particles from cryoelectron microscope images by an ab initio algorithm is
      described. The method begins with a novel linear reconstruction method that
      generates a spherically symmetric reconstruction, which is followed by a
      nonlinear reconstruction method implementing an expectation-maximization
      procedure using the spherically symmetric reconstruction as an initial condition
      and resulting in a reconstruction with icosahedral symmetry. An important
      characteristic of the complete method is that very little need be known about the
      particle before the reconstruction is computed, in particular, only the type of
      symmetry and inner and outer radii. The method is demonstrated on synthetic
      cowpea mosaic virus data, and its robustness to 5% errors in the contrast
      transfer function, 5% errors in the location of the center of the particles in
      the images, and 5% distortion in the 3-D structure from which the images are
      derived is demonstrated numerically.

PMID- 11472086
TI  - Alignment error envelopes for single particle analysis.
AB  - To determine the structure of a biological particle to high resolution by
      electron microscopy, image averaging is required to combine information from
      different views and to increase the signal-to-noise ratio. Starting from the
      number of noiseless views necessary to resolve features of a given size, four
      general factors are considered that increase the number of images actually
      needed: (1) the physics of electron scattering introduces shot noise, (2) thermal
      motion and particle inhomogeneity cause the scattered electrons to describe a
      mixture of structures, (3) the microscope system fails to usefully record all the
      information carried by the scattered electrons, and (4) image misalignment leads
      to information loss through incoherent averaging. The compound effect of factors
      2-4 is approximated by the product of envelope functions. The problem of
      incoherent image averaging is developed in detail through derivation of five
      envelope functions that account for small errors in 11 "alignment" parameters
      describing particle location, orientation, defocus, magnification, and beam tilt.
      The analysis provides target error tolerances for single particle analysis to
      near-atomic (3.5 A) resolution, and this prospect is shown to depend critically
      on image quality, defocus determination, and microscope alignment.

PMID- 11472087
TI  - Bsoft: image and molecular processing in electron microscopy.
AB  - Software for the processing of electron micrographs in structural biology suffers
      from incompatibility between different packages, poor definition and choice of
      conventions, and a lack of coherence in software development. The solution lies
      in adopting a common philosophy of interaction and conventions between the
      packages. To understand the choices required to have such common interfaces, I am
      developing a package called "Bsoft." Its foundations lie in the variety of
      different image file formats used in electron microscopy-a continually
      frustrating experience to the user and programmer alike. In Bsoft, this problem
      is greatly diminished by support for many different formats (including MRC,
      SPIDER, IMAGIC, SUPRIM, and PIF) and by separating algorithmic issues from image
      format-specific issues. In addition, I implemented a generalized functionality
      for reading the tag-base STAR (self-defining text archiving and retrieval)
      parameter file format as a mechanism to exchanging parameters between different
      packages. Bsoft is written in highly portable code (tested on several Unix
      systems and under VMS) and offers a continually growing range of image processing
      functionality, such as Fourier transformation, cross-correlation, and
      interpolation. Finally, prerequisites for software collaboration are explored,
      which include agreements on information exchange and conventions, and tests to
      evaluate compatibility between packages.

PMID- 11472088
TI  - Adopting a database as a solution to managing electron image data.
AB  - A database was used for data management and interprogram communication in an
      image processing and three-dimensional reconstruction program suite for
      biological bundles. The programs were modified from the MRC crystallographic
      package. The database server works with local and remote programs and data sets,
      allows simultaneous requests from multiple clients, and maintains multiple
      databases and data tables within them. It has built-in security for the data
      access. Several graphical user interfaces are available to view and/or edit data
      tables. In addition, FORTRAN interface and function libraries are written to
      communicate with image processing software. The data management overhead is
      inexpensive, requiring only narrow bandwidth from the network. It easily handles
      several data tables with over 1000 entries.

PMID- 11472089
TI  - Lumbricus terrestris hemoglobin--the architecture of linker chains and structural
      variation of the central toroid.
AB  - The extracellular giant hemoglobin from the earthworm Lumbricus terrestris was
      reconstructed at 14.9-A resolution from cryo-electron microscope images, using a
      new procedure for estimating parameters of the contrast transfer (CTF) function.
      In this approach, two important CTF parameters, defocus and amplitude contrast
      ratio, can be refined iteratively within the framework of 3D projection alignment
      procedure, using minimization of sign disagreement between theoretical CTF and
      cross-resolution curves. The 3D cryo-EM map is in overall good agreement with the
      recent X-ray crystallography map of Royer et al. (2000, Proc. Natl. Acad. Sci.
      USA 97, 7107-7111), and it reveals the local threefold arrangement of the three
      linker chains present within each 1/12 of the complex. The 144 globin chains and
      36 linker chains within the complex are clearly visible, and the interdigitation
      of the 12 coiled-coil helical spokes forming the central toroidal piece is
      confirmed. Based on these findings, two mechanisms of the dodecameric unit
      assembly are proposed and termed "zigzag" and "pairwise" polymerizations.
      However, the detection by cryo-EM of 12 additional rod-like bodies within the
      toroid raises the possibility that the architecture of the toroid is more complex
      than previously thought or that yet unknown ligands or allosteric effectors for
      this oxygen carrier are present.

PMID- 11472090
TI  - Using situs for flexible and rigid-body fitting of multiresolution single
      molecule data.
AB  - We describe here a set of multiresolution visualization and docking procedures
      that we refer to as the Situs package. The package was developed to provide an
      efficient and robust method for the fitting of atomic structures into low
      resolution data. The current release was optimized specifically for the
      visualization and docking of single molecules. A novel 3D graphics viewer,
      volslice3d, was developed for the package to provide an immersive virtual reality
      environment for measuring and rendering volumetric data sets. The precision of
      single-molecule, rigid-body docking was tested on simulated (noise-free) low
      resolution density maps. For spatial resolutions near 20 A typically arising in
      electron microscopy image reconstructions, a docking precision on the order of 1
      A can be achieved. The shape-matching score captured the correct solutions in all
      10 trial cases and was sufficiently stringent to yield unique matches in 8
      systems. Novel routines were developed for the flexible docking of atomic
      structures whose shape deviates from the corresponding low-resolution shape. Test
      calculations on isoforms of actin and lactoferrin demonstrate that the flexible
      docking faithfully reproduces conformational differences with a precision < 2 A
      if atomic structures are locally conserved.

PMID- 11472091
TI  - Classification and reconstruction of a heterogeneous set of electron microscopic
      images: a case study of GroEL-substrate complexes.
AB  - Image analysis methods were used to separate images of a large macromolecular
      complex, the chaperonin GroEL, in a preparation in which it is partially liganded
      to a nonnative protein substrate, glutamine synthetase. The relatively small
      difference ( approximately 6%) in size between the chaperonin in its free and
      complexed forms, and the absence of gross changes in overall conformation, made
      separation of the two types of particles challenging. Different approaches were
      evaluated and used for alignment and classification of images, both in two common
      projections and in three dimensions, yielding 2D averages and a 3D
      reconstruction. The results of 3D analysis describe the conformational changes
      effected by binding of this particular protein substrate and demonstrate the
      utility of 2D analysis as an indicator of structural change in this system.

PMID- 11472092
TI  - Dealing with particles in different conformational states by electron microscopy
      and image processing.
AB  - Electron microscopy and image processing are powerful tools for investigating
      different conformational states of enzymes. It is not always possible to isolate
      these often unstable intermediates as single species. As a result electron
      micrographs show a snapshot of enzymes in various conformational states. We
      describe here how to recognize that the imaged particles have different
      conformations and how to obtain for each species a three-dimensional model using
      single-particle image processing. We investigated the ATP synthase from
      chloroplasts, which has a molecular mass of about 550 kDa. It is a membrane-bound
      enzyme and consists of two segments, a membrane-embedded hydrophobic F(0) part
      and a hydrophilic F(1) part. Analysis of the particle images indicated that the
      molecules were in two different conformations. For both conformations three
      dimensional models were calculated, which showed that the structures differed
      mainly in the tilt of the F(0) part with respect to the F(1) part.

PMID- 11472093
TI  - Real space refinement of acto-myosin structures from sectioned muscle.
AB  - We have adapted a real space refinement protocol originally developed for high
      resolution crystallographic analysis for use in fitting atomic models of actin
      filaments and myosin subfragment 1 (S1) to 3-D images of thin-sectioned, plastic
      embedded whole muscle. The rationale for this effort is to obtain a refinement
      protocol that will optimize the fit of the model to the density obtained by
      electron microscopy and correct for poor geometry introduced during the manual
      fitting of a high-resolution atomic model into a lower resolution 3-D image. The
      starting atomic model consisted of a rigor acto-S1 model obtained by X-ray
      crystallography and helical reconstruction of electron micrographs. This model
      was rebuilt to fit 3-D images of rigor insect flight muscle at a resolution of 7
      nm obtained by electron tomography and image averaging. Our highly constrained
      real space refinement resulted in modest improvements in the agreement of model
      and reconstruction but reduced the number of conflicting atomic contacts by 70%
      without loss of fit to the 3-D density. The methodology seems to be well suited
      to the derivation of stereochemically reasonable atomic models that are
      consistent with experimentally determined 3-D reconstructions computed from
      electron micrographs.

PMID- 11472094
TI  - A novel neural network technique for analysis and classification of EM single
      particle images.
AB  - We propose a novel self-organizing neural network for the unsupervised
      classification of electron microscopy (EM) images of biological macromolecules.
      The radical novelty of the algorithm lies in its rigorous mathematical
      formulation that, starting from a large set of possibly very noisy input data,
      finds a set of "representative" data items, organized onto an ordered output map,
      such that the probability density of this set of representative items resembles
      at its possible best the probability density of the input data. In a way, it
      summarizes large amounts of information into a concise description that
      rigorously keeps the basic pattern of the input data distribution. In this
      application to the field of three-dimensional EM of single particles, two
      different data sets have been used; one comprised 2458 rotational power spectra
      of individual negative stain images of the G40P helicase of Bacillus subtilis
      bacteriophage SPP1, and the other contained 2822 cryoelectron images of SV40
      large T-antigen. Our experimental results prove that this technique is indeed
      very successful, providing the user with the capability of exploring complex
      patterns in a succinct, informative, and objective manner. The above facts,
      together with the consideration that the integration of this new algorithm with
      commonly used software packages is immediate, prompt us to propose it as a
      valuable new tool in the analysis of large collections of noisy data.

PMID- 11472095
TI  - Structure analysis of the flagellar cap-filament complex by electron
      cryomicroscopy and single-particle image analysis.
AB  - The cap of the bacterial flagellum plays an essential role in the growth of the
      long helical filament by promoting the efficient self-assembly of flagellin
      transported to the distal end through the narrow central channel of the
      flagellum. The structure of the cap-filament complex was analyzed by electron
      cryomicroscopy and single-particle image analysis to understand how the cap stays
      attached while allowing the flagellin insertion between the cap and the filament
      end and also allowing the HAP proteins to pass through. In the images of the
      complex, the projection pattern of the helical subunit array in the filament
      portion occupied the major fraction but was variable depending on the azimuthal
      orientation of the filament; therefore the images showed a strong tendency to be
      misaligned. Various methods had to be newly developed to correctly align the
      images by overcoming this misalignment problem. The structure thus obtained
      clearly demonstrated the pentameric structure of the cap and how the cap
      operates. The new methods of analysis presented here would be generally
      applicable to cap structures of various filaments that play biologically
      important roles in cellular activities.

PMID- 11472097
TI  - Germline gene therapy: yes or no?

PMID- 11472096
TI  - Single-particle approaches in the analysis of small 2D crystals of the
      mitochondrial channel VDAC.
AB  - It has been difficult to obtain better than moderate resolution in analysis of
      electron microscopic images of small, 2D crystals with variable lattice
      parameters, e.g., crystals of the channel VDAC generated by phospholipase
      treatment of outer mitochondrial membranes. We demonstrate that applying single
      particle analysis methods to correlation-averaged images can lead to significant
      improvements in the attainable resolution. Application of a soft-edged fitted
      mask passing only the central unit cell, and excluding the positionally variable
      adjacent unit cells, allows improved alignment and more sensitive multivariate
      statistical analysis, needed to guide intelligent merging of data from different
      crystals.

PMID- 11472098
TI  - Desire and need: understanding hemophiliacs' participation in gene therapy
      trials.

PMID- 11472099
TI  - Re.:"A Death in the Laboratory".

PMID- 11472100
TI  - Enhanced apoptotic activity of a p53 variant in tumors resistant to wild-type p53
      treatment.
AB  - TP53 is the most commonly altered tumor-suppressor gene in cancer and is
      currently being tested in Phase II/III gene replacement trials. Many tumors
      contain wild-type TP53 sequence with elevated MDM2 protein levels, targeting p53
      for degradation. These tumors are more refractory to treatment with exogenous
      wild-type p53. Here we generate a recombinant adenovirus expressing a p53
      variant, rAd-p53 (d 13-19), that is deleted for the amino acid sequence necessary
      for MDM2 binding (amino acids 13-19). We compared the apoptotic activity of rAd
      p53 (d 13-19) with that of a recombinant adenovirus expressing wild-type p53 (rAd
      p53) in cell lines that differ in endogenous p53 status. rAd-p53 (d 13-19) caused
      higher levels of apoptosis in p53 wild-type tumor lines compared with wild-type
      p53 treatment, as measured by annexin V-FITC staining. In p53-altered tumor
      lines, rAd-p53 (d 13-19) showed apoptotic activity similar to that seen with wild
      type p53 treatment. In normal cells, no increase in cytopathicity was detected
      with rAd-p53 (d 13-19) compared with wild-type p53 treatment. This variant
      protein displayed synergy with chemotherapeutic agents to inhibit proliferation
      of ovarian and breast cell lines. The p53 variant showed greater antitumor
      activity in an established p53 wild-type tumor compared with treatment with wild
      type p53. The p53 variant represents a means of expanding TP53 gene therapy to
      tumors that are resistant to p53 treatment due to the cellular responses to wild
      type p53.

PMID- 11472101
TI  - Variation in adenovirus receptor expression and adenovirus vector-mediated
      transgene expression at defined stages of the cell cycle.
AB  - Detailed investigations have addressed the infection pathway of recombinant
      adenovirus (Ad) gene transfer vectors, but little attention has been paid to the
      influence of cell physiology on the outcome of Ad infection. Based on
      observations that Ad infection of clonal cell populations show cell-to-cell
      variability in the extent of capsid binding, we hypothesized that the cell cycle
      may influence the outcome of Ad infection. To address this hypothesis, we
      evaluated Ad association with cells in both unsynchronized and pharmacologically
      synchronized cell populations. In unsynchronized cell populations, elevated Ad
      association with cells correlated with expression of cyclin B1, a marker of entry
      into the M phase of mitosis. The same analysis conducted on cell populations that
      were synchronized at M phase (using paclitaxel or nocodazole) or at S phase
      (using aphidicolin) confirmed that M phase cells bound three- to sixfold more
      capsid compared with unsynchronized cells, which are primarily in the G(1) and
      G(2) phases. The elevated association of vectors with cells translated into 2.5-
      to 4-fold greater transgene expression 24 hours after infection. Assessment of
      cell surface expression of Ad receptors demonstrated that both the high-affinity
      coxsackie-adenovirus receptor for Ad fiber protein and the low-affinity alpha(v)
      integrin receptor for Ad penton base protein showed increased cell surface
      expression at M phase (1.5-fold and 2- to 3-fold increases, respectively). These
      data demonstrate that Ad infection of a homogenous population of cells can vary
      depending on the cell cycle stage, with enhanced Ad binding and expression
      correlating with the enhanced expression of Ad receptors during M phase. These
      observations have relevance to understanding the mechanisms of gene transfer by
      Ad vectors and should help in the design of in vivo gene transfer strategies.

PMID- 11472102
TI  - Development of novel formulations that enhance adenoviral-mediated gene
      expression in the lung in vitro and in vivo.
AB  - Despite remarkable progress in the development of both viral and non-viral gene
      delivery vectors for cystic fibrosis therapy, low efficiency of gene transfer to
      the airway epithelium is a major obstacle to clinical application. Here we
      develop formulations that enhance cellular absorption of adenoviral vectors. We
      selected excipients from a panel of pharmaceutically acceptable com-pounds known
      to enhance drug absorption. Transduction efficiency of the virus in the presence
      of each ingredient was assessed in vitro and in vivo. Mannitol and chitosan
      substantially enhanced transduction efficiency in vitro and augmented expression
      in vivo by 4 and 8 log units, respectively. The most successful formulation (a
      blend of sucrose, mannitol, and Pluronic F68) transduced 100% of an A549 cell
      population in vitro and produced areas of intense gene expression in both large
      and small airways in vivo with minimal toxicity. Dose response studies also
      indicate that when placed in this formulation, the viral dose can be lowered by
      1/2 log while maintaining superior levels of transgene expression. This
      formulation also enhanced the physical stability of the virus. No significant
      loss in titer was detected from a lyophilized formulation after storage at 25
      degrees C for 30 days.

PMID- 11472103
TI  - Intra-arterial delivery of a recombinant adenovirus does not increase gene
      transfer to tumor cells in a rat model of metastatic colorectal carcinoma.
AB  - Hepatic artery infusion of adenoviral vectors has been shown to increase
      transduction of certain hepatocellular malignancies in preclinical studies. In
      addition, clinical trials have begun evaluating the efficacy of gene transfer of
      cytotoxic genes to metastatic colorectal tumors through hepatic artery infusion.
      Here we evaluate the extent of gene expression and therapeutic effect following
      various routes of administration of recombinant adenovirus in a rat model of
      metastatic colorectal carcinoma. We administered adenovirus (AdCMVlacZ) to rats
      with established colorectal metastases through infusion into the hepatic artery,
      intravenous infusion, or direct injection into a tumor. Intravenous
      administration resulted in transduction of hepatocytes, but not tumor cells.
      Hepatic arterial administration failed to substantially increase transduction of
      tumor cells. In addition, ligation of the hepatic artery following infusion of
      adenovirus or the addition of lipiodol infusion had no effect on the transduction
      of tumor cells. We administered AdCMVp53 by direct injection into tumors,
      intravenous administration, or hepatic artery infusion to evaluate the delivery
      of a therapeutic gene. Direct injection of AdCMVp53 into established hepatic
      colorectal metastases resulted in a therapeutic response in comparison with both
      hepatic arterial and intravenous infusion of vector. These preclinical studies
      fail to support a strategy of infusion through the hepatic artery of recombinant
      adenovirus targeting tumor cells in the treatment of colorectal cancer liver
      metastases.

PMID- 11472104
TI  - A capsid-modified adenovirus vector devoid of all viral genes: assessment of
      transduction and toxicity in human hematopoietic cells.
AB  - Inefficient gene transfer has limited the success of gene therapy in the
      hematopoietic system. Here we develop a novel chimeric adenovirus (Ad) vector
      containing Ad serotype 11 fiber-modified capsids and E1/E3 deleted viral genomes
      (Ad5/11) or genomes devoid of all viral genes (DeltaAd5/11). The capsid-modified
      vectors transduced human hematopoietic cells more efficiently than the unmodified
      Ad5-based vector. The absence of viral genes from the DeltaAd5/11 vector allowed
      for transduction without the associated toxicity seen with the first-generation
      E1/E3 deleted vector. Chimeric vectors were used for transient expression of the
      ecotropic retrovirus receptor (ecoR) in Mo7e cells (a CD34-positive, c-Kit
      positive, growth-factor-dependent human cell line) as a model for human
      hematopoietic progenitor cells. Expression of ecoR conferred susceptibility to
      subsequent retroviral transduction. The DeltaAd5/11 vector used to express ecoR
      allowed for expansion of retrovirally transduced cells, whereas transduction with
      the first-generation Ad5/11 vector resulted in cytotoxicity and, over time, loss
      of cells expressing the retrovirus-vector-derived transgene.

PMID- 11472105
TI  - Transfer of full-length Dmd to the diaphragm muscle of Dmd(mdx/mdx) mice through
      systemic administration of plasmid DNA.
AB  - Mutations in the gene encoding dystrophin, a large cytoskeletal protein in
      muscle, lead to Duchenne muscular dystrophy (DMD). Affected individuals often die
      of respiratory failure resulting primarily from diaphragm muscle degeneration.
      Here we report a new procedure to transfer the full-length dystrophin cDNA into
      the diaphragm muscle of Dmd(mdx/mdx) mice, which carry a mutation in the
      dystrophin gene (Dmd). Significant gene transfer was found after intravenous
      injection of naked plasmid DNA followed by a brief (eight second) occlusion of
      blood flow at the vena cava. This is the first demonstration of gene transfer
      into the diaphragm muscle through systemic administration of naked plasmid DNA.
      The approach has potential application for treatment of DMD.

PMID- 11472106
TI  - Effects of linear polyethylenimine and polyethylenimine/DNA on lung function
      after airway instillation to rat lungs.
AB  - Lung transplantation is an acceptable treatment option for various end-stage
      pulmonary diseases, but long-term survival currently lags behind that after
      transplantation of other solid organs. We hypothesized that gene transfer to
      grafts before transplantation may be a useful method to deliver antioxidant
      and/or anti-inflammatory genes to modulate these processes. For this purpose, we
      assessed the efficiency of gene transfer and effects on lung function of the
      synthetic polycation, linear polyethylenimine (PEI), after airway instillation to
      the lungs of Fischer rats. Twenty-four hours after gene delivery, reporter gene
      activity in DNA/PEI treated rats was approximately 12-fold higher than that in
      rats treated with naked DNA, but by 72 hours there was no significant difference
      between groups and activity had decreased by at least 85%. Function of the
      transfected left lung was assessed by measuring arterial PaO(2) levels and was
      found to be significantly lower at 24 and 72 hours after gene transfer in the
      PEI/DNA group compared with the naked DNA group. The deterioration in lung
      function correlated with histological findings. Rats treated with PEI alone and
      sacrificed after 72 hours showed an impairment in lung function similar to that
      seen with PEI/DNA treatment. Our studies highlight the importance of assessing
      the functional capacity of a graft after gene transfer to determine suitability
      for subsequent transplantation.

PMID- 11472107
TI  - Targeting transgene expression for cystic fibrosis gene therapy.
AB  - We have developed an expression cassette for cystic fibrosis (CF) gene therapy
      using control elements from the human cytokeratin 18 gene (KRT18, also known as
      K18). KRT18 is naturally expressed in a spatial pattern similar to that of CFTR,
      the gene mutated in CF. We delivered a KRT18-driven lacZ plasmid complexed with
      cationic liposomes intravenously to mice and examined expression in various
      tissues. We found expression in nasal and bronchial epithelium, airway submucosal
      glands, gall bladder, and kidneys. Expression was low in pancreas and gut, and
      absent from liver and alveolar lung. This is consistent with the expression
      pattern reported for a K18lacZ transgenic mouse. Following delivery of a
      cytomegalovirus (CMV) major immediate-early promoter/enhancer-driven lacZ
      plasmid, we found expression in bronchi, submucosal glands, alveolar cells,
      liver, and kidney. We did not detect expression in nose, pancreas, gall bladder,
      or gut. Using fluorescently labeled plasmid delivered by means of liposomes, we
      identified the liver, alveolar lung, and kidneys as the major plasmid deposition
      sites. Our data demonstrate that a KRT18-driven expression vector delivered
      systemically can target gene expression to CF-affected tissues, despite an uneven
      distribution of plasmid DNA. A KRT18-based vector may be a useful alternative to
      viral promoter-based vectors in clinical gene therapy trials to treat CF.

PMID- 11472108
TI  - Optimization of a peptide/non-cationic lipid gene delivery system for effective
      microinjection into chicken embryo in vivo.
AB  - Here we report the characterization and optimization of a peptide/non-cationic
      lipid gene delivery system that successfully produces high levels of gene
      expression when delivered by microinjection into chicken embryos in vivo. In
      addition to plasmid DNA, the delivery complex consisted of four components: 1) a
      "condensing" peptide with both hydrophobic and cationic amino acid segments; 2) a
      "fusogenic" peptide with both membrane insertion and amphipathic helical
      segments; 3) a relatively short-chain phosphatidylcholine (14:1 cis-9); and 4)
      polyethyleneglycol conjugated to dioleoylphosphatidylethanolamine through a
      disulfide linkage. Optimum amounts of each component were determined by measuring
      expression of a luciferase reporter gene following a 24-hour incubation with
      chick embryo fibroblast (CEF) cells in culture. When relatively low amounts of
      condensing peptide, fusogenic peptide, or lipid were assembled into the
      complexes, relatively large concentrations of complex were required to reach
      maximum gene expression. When the amounts of peptide or lipid were increased,
      less complex was required to achieve maximum expression, but expression fell
      substantially with higher amounts of added complex. The polyethyleneglycol
      component significantly increased gene expression. With some preparations,
      luciferase activities in the CEF cells reached 1x10(10) relative light units per
      second per mg protein within 24 hours. Following the optimization experiments
      with the CEF cells, formulations containing low levels, intermediate levels, and
      high levels of the delivery system components were assembled with green
      fluorescent protein plasmid DNA, then microinjected into somite regions of
      chicken embryos in vivo. It was found that intermediate levels of the components
      gave the most reliable formulations for inducing localized gene expression in the
      somitic cells.

PMID- 11472109
TI  - High and sustained transgene expression in vivo from plasmid vectors containing a
      hybrid ubiquitin promoter.
AB  - Sustained transgene expression will be required for the successful treatment of
      most genetic diseases being considered for gene therapy. The initially high
      levels of expression attained with plasmid DNA (pDNA) vectors containing viral
      promoters, such as that from cytomegalovirus (CMV), decline precipitously to near
      background levels within two to three weeks. Here we constructed pDNA vectors
      containing the human cellular UBB (encoding ubiquitin B; Ub) promoter and
      evaluated their expression in the mouse lung. Cationic lipid-pDNA complexes were
      instilled intranasally (IN) or injected intravenously (IV) into immunodeficient
      BALB/c mice. Chloramphenicol acetyltransferase (CAT) reporter gene expression
      from the UBB promoter was initially very low at day 2 post-administration, but by
      day 35 exceeded the level of expression attained from a CMV promoter vector by
      four- to ninefold. Appending a portion of the CMV enhancer 5' of the UBB promoter
      (CMV-Ub) increased CAT expression to nearly that of the CMV promoter and
      expression persisted in the lung for at least 3 months, with 50% of day 2 levels
      remaining at day 84. In the liver, expression from the CMV-Ub hybrid promoter was
      sustained for 42 days. As previous studies have shown that eliminating
      immunostimulatory CpG motifs in pDNA vectors reduces their toxicity, we
      constructed a CpG-deficient version of the CMV-Ub vector expressing alpha
      galactosidase A, the enzyme deficient in Fabry disease, a lysosomal storage
      disorder. After IN or IV administration, levels of alpha-galactosidase A from
      this vector were not only undiminished but increased 500% to 1500% by day 35. Our
      results indicate that CpG-reduced plasmid vectors containing a CMV-Ub hybrid
      promoter may provide the long-term expression required for a practical gene
      therapeutic.

PMID- 11472110
TI  - Synthesis and characterization of DNA duplexes containing an N(4)C-ethyl-N(4)C
      interstrand cross-link.
AB  - Short DNA duplexes containing an N(4)C-ethyl-N(4)C interstrand cross-link, C-C,
      were synthesized on controlled pore glass supports. Duplexes having two, three,
      or four A/T base pairs on either side of the C-C cross-link and terminating with
      a C(4) overhang at their 5'-ends were prepared. The cross-link was introduced
      using a convertible nucleoside approach. Thus, an oligonucleotide terminating at
      its 5'-end with O(4)-triazoyl-2'-deoxyuridine was first prepared on the support.
      The triazole group of support-bound oligomer was displaced by the aminoethyl
      group of 5'-dimethoxytrityl-3'-O-tert-butyldimethylsilyl-N(4)-(2
      aminoethyl)deoxycytidine to give the cross-link. The dimethoxytrityl group was
      removed, and the upper and lower strands of the duplex were extended from two 5'
      hydroxyl groups of the cross-link using protected nucleoside 3'-phosphoramidites.
      The tert-butyldimethylsilyl group of the resulting partial duplex was then
      removed, and the chain was extended in the 3'-direction from the resulting 3'
      hydroxyl of the cross-link using protected nucleoside 5'-phosphoramidites. The
      cross-linked duplexes were purified by HPLC and characterized by enzymatic
      digestion and MALDI-TOF mass spectrometry. Duplexes with three or four A/T base
      pairs on either side of the C-C cross-link gave sigmoidal shaped A(260) profiles
      when heated, a behavior consistent with cooperative denaturation of the A/T base
      pairs. Each cross-linked duplex could be ligated to an acceptor duplex using T4
      DNA ligase, a result that suggests that the C-C cross-link does not interfere
      with the ligation reaction, even when it is located only two base pairs from the
      site of ligation. The ability to synthesize duplexes with a defined interstrand
      cross-link and to incorporate these duplexes into longer pieces of DNA should
      enable preparation of substrates that can be used for a variety of biophysical
      and biochemical experiments, including studies of DNA repair.

PMID- 11472111
TI  - Reversible pressure deformation of a thermophilic cytochrome P450 enzyme (CYP119)
      and its active-site mutants.
AB  - The pressure stability of the thermophilic CYP119 from Sulfolobus solfataricus
      and its active-site Thr213 and Thr214 mutants was investigated. At 20 degrees C
      and pH 6.5, the protein undergoes a reversible P450-to-P420 inactivation with a
      midpoint at 380 MPa and a reaction volume change of -28 mL/mol. The volume of
      activation of the process was -9.5 mL/mol. The inactivation transition was
      retarded, and the absolute reaction volume was decreased by increasing
      temperature or by mutations that decrease the size of the active-site cavity.
      High pressure affected the tryptophan fluorescence yield, which decreased by
      about 37% at 480 MPa. The effect was reversible and suggested considerable
      contraction of the protein. Aerobic decomposition of iron-aryl complexes of the
      CYP119 T213A mutant under increasing hydrostatic pressure resulted in variation
      of the N-arylprotoporphyrin-IX regioisomer (N(B):N(A):N(C):N(D)) adduct pattern
      from 39:47:07:07 at 0.1 MPa to 23:36:14:27 at 400 MPa. Preincubation of the
      protein at 400 MPa followed by complex formation and decomposition gave the same
      regioisomer distribution as untreated protein. The results indicate that the
      protein is reversibly inactivated by pressure, in contrast to the irreversible
      inactivation of P450(cam) and other P450 enzymes, and that this inactivation
      process is modulated by changes in the active-site cavity dimensions.

PMID- 11472112
TI  - Energetically most likely substrate and active-site protonation sites and
      pathways in the catalytic mechanism of dihydrofolate reductase.
AB  - Despite much experimental and computational study, key aspects of the mechanism
      of reduction of dihydrofolate (DHF) by dihydrofolate reductase (DHFR) remain
      unresolved, while the secondary DHFR-catalyzed reduction of folate has been
      little studied. Major differences between proposed DHF mechanisms are whether the
      carboxylate group of the conserved active-site Asp or Glu residue is protonated
      or ionized during the reaction, and whether there is direct protonation of N5 or
      a proton shuttle from an initially protonated carboxylate group via O4. We have
      addressed these questions for both reduction steps with a comprehensive set of ab
      initio quantum chemical calculations on active-site fragment complexes, including
      the carboxyl side chain and, progressively, all other polar active-site residue
      groups including conserved water molecules. Addition of two protons in two steps
      was considered. The polarization effects of the remainder of the enzyme system
      were approximated by a dielectric continuum self-consistent reaction field (SCRF)
      model using an effective dielectric constant (epsilon) of 2. Optimized geometries
      were calculated using the density functional (B3LYP) method and Onsager SCRF
      model with the 6-31G basis. Single-point energy calculations were then carried
      out at the B3LYP/6-311+G level with either the Onsager or dielectric polarizable
      continuum model. Additional checking calculations at MP2 and HF levels, or with
      other basis sets or values of epsilon, were also done. From the results, the
      conserved water molecule, corresponding to W206 in the E. coli DHFR complexes,
      that is H-bonded to both the OD2 oxygen atom of the carboxyl (Asp) side chain and
      O4 of the pterin/dihydropterin ring, appears critically important and may
      determine the protonation site for the enzyme-bound substrates. In the absence of
      W206, the most stable monoprotonated species are the neutral-pair 4-enol forms of
      substrates with the carboxyl group OD2 oxygen protonated and H-bonded to N3. If
      W206 is included, then the most stable forms are still the neutral-pair complexes
      but now for the N3-H keto forms with the protonated OD2 atom H-bonding with W206.
      A second proton addition to these complexes gives protonations at N8 (folate) or
      N5 (DHF). Calculated H-bond distances correlate well with those for the conserved
      W206 observed in many X-ray structures. For all structures with occluded M20 loop
      conformations (closed active site), OD2-N3 distances are less than OD2-NA2
      distances, which is consistent with those calculated for protonated OD2
      complexes. Thus, the results (B3LYP; epsilon = 2 calculations) support a
      mechanism for both folate and DHF reduction in which the OD2 carboxyl oxygen is
      first protonated, followed by a direct protonation at N8 (folate) and N5 (DHF) to
      obtain the active cation complexes, i.e., doubly protonated. The results do not
      support a proposed protonated carboxyl with DHF in the enol form for the
      Michaelis complex, nor an ionized carboxyl with protonated enol-DHF as a
      catalytic intermediate. However, as additional calculations for the
      monoprotonated complete complexes show a reduction in the energy differences
      between the neutral-pair keto and ion-pair keto (N8- or N5-protonated) forms, we
      are extending the treatment using combined quantum mechanics and molecular
      mechanics (QM/MM) and molecular dynamics simulation methods to refine the
      description of the protein/solvent environment and prediction of the relative
      stabilization free energies of the various (OD2, O4, N5, and N8) protonation
      sites.

PMID- 11472113
TI  - Changing the ortho/para ratio in aromatic acylation reactions by changing
      reaction conditions: a mechanistic explanation from kinetic measurements.
AB  - Kinetic measurements of the acylation of toluene (2a) and p-xylene (2b), side
      chain deuterated toluene (2a-d(3)), as well as perdeuterated toluene (2a-d(8))
      and p-xylene (2b-d(10)) with the aroyl triflate 1 in 1,2-dichloroethane reveal a
      strong dependence of the isotope effect on reaction conditions. In the presence
      of trifluoromethanesulfonic acid (HOTf), the second-order rate constants
      k(H)/k(D) observed are in the order of 1.75-1.94, whereas in the presence of
      2,4,6-tri-tert-butylpyridine (4) rate constants k(H)/k(D) of 1.14-1.25 are found.
      The primary kinetic isotope effects observed correlate with the ortho/para ratio
      of the acylation of toluene. In the presence of 4 a relatively high percentage (
      approximately 30%) of ortho product is obtained, whereas under acidic conditions
      the ratio is only 10%. The correlation between isotope effects and isomer
      distributions is obviously due to the rate of deprotonation of the corresponding
      sigma-complex intermediates. Assuming a bent structure for sigma-complexes, the
      conformation giving deprotonation is preferred in the para sigma-complex in
      comparison with ortho complex.

PMID- 11472114
TI  - The antioxidant profile of 2,3-dihydrobenzo[b]furan-5-ol and its 1-thio, 1
      seleno, and 1-telluro analogues.
AB  - A novel synthesis of 2,3-dihydrobenzo[b]thiophene-5-ol based on intramolecular
      homolytic substitution on sulfur was reported. The "antioxidant profile" of the
      series of 2,3-dihydrobenzo[b]furan-5-ol (2a) its 1-thio (2b), 1-seleno (2c) and 1
      telluro (2d) analogues was determined by studies of redox properties, the
      capacity to inhibit stimulated lipid peroxidation, the reactivity toward tert
      butoxyl radicals, the ability to catalyze decomposition of hydrogen peroxide in
      the presence of glutathione, and the inhibiting effect on stimulated peroxidation
      in liver microsomes. The one-electron reduction potentials of the aroxyl radicals
      corresponding to compounds 2a-2d, E degrees (ArO(*)/ArO(-)) were 0.49, 0.49,
      0.49, and 0.52 V vs NHE, respectively, as determined by pulse radiolysis. With
      increasing chalcogen substitution the compounds become slightly more acidic
      (pK(a) = 10.6, 10.0, 9.9, and 9.5, respectively, for compounds 2a-2d). By using
      Hess' law, the homolytic O-H bond dissociation enthalpies of compounds 2a-2d
      (340, 337, 336, and 337 kJ mol(-)(1), respectively) were calculated. The
      reduction potentials for the proton coupled oxidation of compounds 2a-2d (ArOH -
      > ArO(*) + H(+)) as determined by cyclic voltammetry in acetonitrile were 1.35
      (irreversible), 1.35 (quasireversible) 1.13 (reversible), and 0.74 (reversible) V
      vs NHE, respectively. As judged by the inhibited rates of peroxidation, R(inh),
      in a water/chlorobenzene two-phase lipid peroxidation system containing N
      acetylcysteine as a thiol-reducing agent in the aqueous phase, the antioxidant
      capacity increases (2d > 2c = 2b > 2a) as one traverses the group of chalcogens.
      Whereas the times of inhibition, T(inh), were slightly reduced for the oxygen
      (2a) and sulfur (2b) derivatives in the absence of the thiol-reducing agent, they
      were drastically reduced for the selenium (2c) and tellurium (2d) derivatives.
      This seems to indicate that the organochalcogen compounds are continuously
      regenerated at the lipid aqueous interphase and that regeneration is much more
      efficient for the selenium and tellurium compounds. The absolute rate constants
      for the oxidation of compounds 2a-2b by the tert-butoxyl radical in
      acetonitrile/di-tert-butyl peroxide (10/1) were the same-2 x 10(8) M(-)(1) s(
      )(1). Whereas the oxygen, sulfur, and selenium derivatives 2a-2c were essentially
      void of any glutathione peroxidase-like activity, the organotellurium compound 2d
      accelerated the initial reduction of hydrogen peroxide, tert-butyl hydroperoxide,
      and cumene hydroperoxide in the presence of glutathione 100, 333, and 213 times,
      respectively, as compared to the spontaneous reaction. Compounds 2a-2d were
      assessed for their capacity to inhibit lipid peroxidation in liver microsomes
      stimulated by Fe(II)/ADP/ascorbate. Whereas the oxygen, sulfur, and selenium
      compounds showed weak inhibiting activity (IC(50) values of approximately 250,
      25, and 13 microM, respectively), the organotellurium compound 2d was a potent
      inhibitor with an IC(50) value of 0.13 microM.

PMID- 11472115
TI  - Diastereoselective propargylations with planar chiral chromiumcarbonyl arene
      complex substituted propargyl cations.
AB  - The ionization of planar chiral ortho-substituted (arene)Cr(CO)(3)-substituted
      alpha-propargylic acetates 3 with Lewis acids results in the formation of stable
      (arene)Cr(CO)(3)-substituted alpha-propargyl cations 4. Subsequent additions of
      sulfur, nitrogen, oxygen, and pi-carbon nucleophiles to these organometallic
      electrophiles give rise to the regio- and highly diastereoselective formation of
      propargyl derivatives 5 in good yields (44-90%; dr = 70:30 to >99:1). The
      relative stereochemistry of the propargyl acetates 3 and the trapping products 5
      was established by several crystal structure analyses, indicating that the
      cationic propargylations occurred under retention of configuration at the
      propargylic center. Most important for the diastereoselectivity of the
      nucleophilic trapping reaction is the configurational stability of the
      diastereotopic cation 4 as reflected by substituent effects. In situ ionizations
      according to an S(N)1-mechanism not only result in a considerable loss but also
      in an inversion of diastereoselectivity.

PMID- 11472116
TI  - Methylammonium groups at the solid walls of nanometer-sized, water-filled
      monolayer gaps as binding sites for a tetraanionic porphyrin.
AB  - Long-chain hydrosulfides containing two secondary amide functions and either
      electron-poor or electron-rich carbon-carbon double bonds were self-assembled on
      gold surfaces around a flat-lying, octaanionic porphyrin. Rigid and reactive
      surface monolayers with 2 nm-wide, porphyrin-based gaps were thus obtained. The
      gold electrodes were then immersed in water, and the double bonds on the gaps'
      surfaces reacted with methylamine. It was added to the double bonds either by
      Michael addition or by bromination with hypobromite followed by methylamine
      substitution. Only the double bonds at the border of the gaps were accessible to
      methylamine dissolved in the bulk water volume and could react. The walls of the
      rigid membrane gaps now contained methylammonium groups at the sites of the
      double bonds in defined heights. A tetracationic copper(II) porphyrinate could
      not diffuse any more into the gap and did not quench the fluorescence of the
      octaanionic porphyrin on the bottom of the gap. A tetraanionic porphyrin, on the
      other hand, was fixated by the ring of ammonium groups. The bound porphyrin then
      acted as molecular cover for the gap with respect to ferricyanide transport from
      bulk water to the electrode. It was removed by raising the pH to a value of 12,
      where the methylammonium groups were neutralized to amines. Lowering the pH to 7
      again and addition of more of the anionic porphyrin reclosed the gap.The
      porphyrin "cover" should be localized at distances of 8-10 and 20 A from the
      bottom porphyrin by multiple charge interactions. The 8-10 A distance is ideal
      for studies of photoinduced electron transfer between two porphyrin monomers of
      different redox potential. Furthermore it was found, that redox-active tyrosine
      could be trapped in the water volume above the porphyrin on gold.

PMID- 11472117
TI  - An allyltitanium derived from acrolein 1,2-dicyclohexylethylene acetal and
      (eta(2)-propene)Ti(O-i-Pr)(2) as a chiral propionaldehyde homoenolate equivalent
      that reacts with imines with excellent stereoselectivity. An efficient and
      practical access to optically active gamma-amino carbonyl compounds.
AB  - A chiral allyltitanium compound 2, prepared in situ by the reaction of optically
      active acrolein 1,2-dicyclohexylethylene acetal (3) with (eta(2)-propene)Ti(O-i
      Pr)(2) (1), reacts with a variety of acyclic and cyclic imines 4 in a
      regiospecific way to afford alpha-addition products 5 as a mixture of the E- and
      Z-isomers in good combined yield, where the former is predominant in a ratio of
      92:8 to >95:5. The mixture of (E)- and (Z)-5 and pure (E)-5 which could be
      isolated in several cases were respectively converted to the corresponding beta
      amino ester 6 to confirm the absolute configuration and enantiomeric purity. The
      ee of the newly formed asymmetric center of 5 is more than 78% for the mixture of
      (E)- and (Z)-5 and more than 96% for pure (E)-5. By taking advantage of the
      versatility of the vinyl ether moiety in 5, optically active gamma-amino
      aldehydes 8, gamma-amino aldehyde acetals 7 and 10, gamma-amino acids 9, beta
      amino esters 6, and pyrrolidinoisoquinolines 12 were readily prepared. In the
      reaction of 2 with optically active alpha-silyloxyimine 4n, remarkable double
      stereodifferentiation was observed; thus, the reaction of 2 derived from (S,S)-
      or (R,R)-3 provided syn- and anti-5n in a ratio of 55:45 or 0:100, respectively.
      Meanwhile, the stereochemistry of the product in the reaction of 2 with beta
      silyloxyimine 4o was controlled mainly by 2. Thus, the reaction of beta
      silyloxyimine 14 with 2 derived from 1 and (R,R)-3 afforded gamma-silyloxyimine
      15 with 92% diastereoselectivity, from which 4-amino-6-hydroxypentadecanal
      dimethyl acetal (13), a key intermediate for the synthesis of batzelladine D, was
      synthesized.

PMID- 11472118
TI  - Stereocontrolled asymmetric synthesis of alpha-hydroxy-beta-amino acids. A
      stereodivergent approach.
AB  - The stereocontrolled asymmetric synthesis of alpha-hydroxy-beta-amino acids has
      been investigated via the Lewis acid-promoted cyanation of (5R,6S)-2-acetoxy-4
      (benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazines with
      trimethylsilyl cyanide. Base-catalyzed hydrolysis of the resulting cyano
      compounds proceeds with excellent stereoselectivity, providing access to
      diastereomerically pure oxazine-2-carboxylic acids which were readily converted
      to each enantiomer of the alpha-hydroxy-beta-amino acids isothreonine and nor-C
      statine.

PMID- 11472119
TI  - Use of aromatic radical-anions in the absence of THF. Tandem formation and
      cyclization of benzyllithiums derived from the attack of homo- and
      bishomoallyllithiums on alpha-methylstyrenes: two-pot synthesis of cuparene.
AB  - When a homo- or bishomoallyllithium, generated by reductive lithiation of the
      corresponding phenyl thioether by the radical anion lithium 1
      (dimethylamino)naphthalenide (LDMAN), is added to alpha-methylstyrene, a tandem
      addition/cyclization to a phenyl-substituted five- or six-membered-ring occurs.
      The yields are compromised by polymerization of the alpha-methylstyrene, a
      process favored by tetrahydrofuran (THF), the solvent used to generate lithium
      aromatic radical anions. Thus, a new method of generating LDMAN (unsuccessful for
      other common radical anions) in the absence of THF has been developed. The
      radical anion can be generated and the reductive lithiation performed in dimethyl
      ether at -70 degrees C. After the addition of diethyl ether or other solvent, and
      evaporation of the dimethyl ether in vacuo, the alpha-methylstyrene is added and
      the solution is warmed to -30 degrees C. When the unsaturated alkyllithium is
      primary, no adduct forms in THF due to polymerization of the alpha-methylstyrene,
      but moderate yields are attained in a solvent containing mainly hexanes. It was
      also found that the cyclized organolithiums, which would have become protonated
      in the presence of THF, can be captured by an electrophile, even at ambient
      temperature. A two-pot synthesis, the most efficient reported, of the
      sesquiterpene (+/-)-cuparene in 46% yield, using this technology is reported.

PMID- 11472120
TI  - Partially bridge-fluorinated dimethyl bicyclo[1.1.1]pentane-1,3-dicarboxylates:
      preparation and NMR spectra.
AB  - Direct fluorination of dimethyl bicyclo[1.1.1]pentane-1,3-dicarboxylate, obtained
      from [1.1.1]propellane prepared by an improved synthetic procedure, furnished
      esters of 14 of the 15 possible bridge-fluorinated bicyclo[1.1.1]pentane-1,3
      dicarboxylic acids, isolated by preparative GC. Calculated geometries reflect the
      substitution pattern in a regular fashion compatible with Bent's rules.
      Considerable additional strain is introduced into the bicyclo[1.1.1]pentane cage
      by polyfluorination; it is calculated to be as high as 33-35 kcal/mol for
      hexasubstitution. Three arrangements of the fluorine substituents are especially
      strain-rich: geminal, proximate, and W-related. The (1)H, (13)C, and (19)F NMR
      spectra exhibit a striking variety of chemical shifts and long-range coupling
      constants. These are in good agreement with results calculated with neglect of
      the bridgehead substituents for all of the chemical shifts by the GIAO-RHF/6
      31G//RHF/6-31G and GIAO-RHF/6-31G//MP2/6-31G methods and for many of the coupling
      constants by the EOM-CCSD/6-311G//MP2/6-311G method. The proximate (4)J(FF)
      constants are particularly large (50-100 Hz) and show an inverse linear
      dependence on the calculated F-F distance in the range 2.43-2.58 A.

PMID- 11472121
TI  - A calix[4]arene ureidopeptide dimer self-assembled through two superposed
      hydrogen bond arrays.
AB  - Dimerization of calix[4]arene ureidopeptides is demonstrated for the first time.
      Two calix[4]arenes tetrasubstituted in the upper rim with 
      NHCONH(L)LeuNHC(8)H(17) (1) and -NHCONH(L)Leu(D)Leu-OMe (2) were prepared and
      studied by NMR, circular dicroism, and gel permeation chromatography. Compound 2
      self-assembles through urea-urea hydrogen bonds, as well as by an additional set
      of hydrogen bonds provided by the peptide side chains, with participation of the
      ester carbonyls. The absence of such group in 1 causes the monomer structure to
      be favored in this case.

PMID- 11472122
TI  - Neighboring side chain effects on asparaginyl and aspartyl degradation: an ab
      initio study of the relationship between peptide conformation and backbone NH
      acidity.
AB  - The rate of spontaneous degradations of asparagine and aspartyl residues
      occurring through succinimide intermediates is dependent upon the nature of the
      residue on the carboxyl side in peptides. For nonglycine residues, we show here
      that this effect can largely be attributed to the electrostatic/inductive effect
      of the side chain group on the equilibrium concentration of the anionic form of
      the peptide bond nitrogen atom that initiates the succinimide forming reaction.
      However, the rate of degradation of Asn-Gly and Asp-Gly containing peptides is
      about an order of magnitude greater than predicted solely using this explanation.
      To understand the nature of the glycine effect, ab initio calculations were
      performed on model compounds. These calculations indicate that there is little to
      no change in the stability of the transition state or the tetrahedral
      intermediate of succinimide formation with Asn-/Asp-Gly and Asn-/Asp-Ala
      derivatives. However, we have found that the acidity of the backbone peptide
      nitrogen NH is highly dependent upon the conformation of the molecule. Since
      glycine residues lack the beta-carbon common to all other protein amino acids,
      these residues can sample additional regions of conformational space where it is
      possible to further stabilize the backbone amide anion and thus increase the rate
      of degradation. These results provide the first rationale for the particular rate
      enhancement of degradation in peptidyl Asn-/Asp-Gly sequences. The results also
      can be applied to asparagine and aspartyl residues in proteins where the 3
      dimensional structure provides additional constraints on conformation that can
      either increase or decrease the equilibrium concentration of the backbone amide
      anion and thus their rate of degradation via succinimide intermediates.
      Understanding this chemistry will assist attempts to minimize the deleterious
      effect of aging at the molecular level. The relationship between these results
      and proton exchange experiments is discussed in the Appendix.

PMID- 11472123
TI  - Frequency selective heteronuclear dipolar recoupling in rotating solids: accurate
      (13)C-(15)N distance measurements in uniformly (13)C,(15)N-labeled peptides.
AB  - We describe a magic-angle spinning NMR experiment for selective (13)C-(15)N
      distance measurements in uniformly (13)C,(15)N-labeled solids, where multiple
      (13)C-(15)N and (13)C-(13)C interactions complicate the accurate measurement of
      structurally interesting, weak (13)C-(15)N dipolar couplings. The new experiment,
      termed FSR (frequency selective REDOR), combines the REDOR pulse sequence with a
      frequency selective spin-echo to recouple a single (13)C-(15)N dipolar
      interaction in a multiple spin system. Concurrently the remaining (13)C-(15)N
      dipolar couplings and all (13)C-(13)C scalar couplings to the selected (13)C are
      suppressed. The (13)C-(15)N coupling of interest is extracted by a least-squares
      fit of the experimentally observed modulation of the (13)C spin-echo intensity to
      the analytical expression describing the dipolar dephasing in an isolated
      heteronuclear spin pair under conventional REDOR. The experiment is demonstrated
      in three uniformly (13)C,(15)N-labeled model systems: asparagine, N-acetyl-L-Val
      L-Leu and N-formyl-L-Met-L-Leu-L-Phe; in N-formyl-[U-(13)C,(15)N]L-Met-L-Leu-L
      Phe we have determined a total of 16 internuclear distances in the 2.5-6 A range.

PMID- 11472124
TI  - Supported metallocene catalysts by surface organometallic chemistry. Synthesis,
      characterization, and reactivity in ethylene polymerization of oxide-supported
      mono- and biscyclopentadienyl zirconium alkyl complexes: establishment of
      structure/reactivity relationships.
AB  - The reactions of CpZr(CH(3))(3), 1, and Cp(2)Zr(CH(3))(2), 2, with partially
      dehydroxylated silica, silica-alumina, and alumina surfaces have been carried out
      with careful identification of the resulting surface organometallic complexes in
      order to probe the relationship between catalyst structure and polymerization
      activity. The characterization of the supported complexes has been achieved in
      most cases by in situ infrared spectroscopy, surface microanalysis, qualitative
      and quantitative analysis of evolved gases during surface reactions with labeled
      surface, solid state (1)H and (13)C NMR using (13)C-enriched compounds, and
      EXAFS. 1 and 2 react with silica(500) and silica-alumina(500) by simple
      protonolysis of one Zr-Me bond by surface silanols with formation of a single
      well-defined neutral compound. In the case of silica-alumina, a fraction of the
      supported complexes exhibits some interactions with electronically unsaturated
      surface aluminum sites. 1 and 2 also react with the hydroxyl groups of gamma
      alumina(500), leading to several surface structures. Correlation between EXAFS
      and (13)C NMR data suggests, in short, two main surface structures having
      different environments for the methyl group: [Al](3)-OZrCp(CH(3))(2) and [Al](2)
      OZrCp(CH(3))(mu-CH(3))-[Al] for the monoCp series and [Al](2)-OZrCp(2)(CH(3)) and
      [Al]-OZrCp(2)(mu-CH(3))-[Al] for the bisCp series. Ethylene polymerization has
      been carried out with all the supported complexes under various reaction
      conditions. Silica-supported catalysts in the absence of any cocatalyst exhibited
      no activity whatsoever for ethylene polymerization. When the oxide contained
      Lewis acidic sites, the resulting surface species were active. The activity,
      although improved by the presence of additional cocatalysts, remained very low by
      comparison with that of the homogeneous metallocene systems. This trend has been
      interpreted on the basis of various possible parameters, including the (p-pi)-(d
      pi) back-donation of surface oxygen atoms to the zirconium center.

PMID- 11472125
TI  - Interfacial and intrafacial linkage isomerizations of rhenium complexes with
      aromatic molecules.
AB  - The mechanisms for the interconversion of facial diastereomers of a variety of
      TpRe(CO)(L)(eta(2)-L(Ar)) complexes [L = (t)BuNC, pyridine (py), PMe(3), or 1
      methylimidazole (MeIm); L(Ar) = benzene, anisole, naphthalene, 1-methylpyrrole,
      furan, or thiophene; Tp = hydridotris(pyrazolyl)borate] have been investigated by
      (1)H NMR spin saturation experiments. In addition, the rates and free energies of
      activation for these processes were calculated from spin saturation experiments
      and T(1) measurements. The operative mechanisms for interconversion of the pi
      diastereomers were found to be nondissociative, undergoing either an interfacial
      or intrafacial linkage isomerization. A comparison of the kinetic parameters for
      isomerization of related eta(2)-olefin complexes of the [TpRe(CO)(PMe(3))] and
      [CpRe(NO)(PPh(3))](+) fragments is also presented.

PMID- 11472126
TI  - Synthesis of [Ru(phen)(2)dppz](2+)-tethered oligo-DNA and studies on the
      metallointercalation mode into the DNA duplex.
AB  - To explore the binding properties of [Ru(phen)(2)dppz](2+) complex (phen = 1,10
      phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine) in a sequence-specific
      manner in DNA duplex, it was tethered through the dppz ligand to a central
      position as well as both at the 3'- and 5'-ends of oligodeoxyribonucleotide
      (ODN). The middle [Ru(phen)(2)dppz](2+)-ODN tethered was resolved and isolated as
      four pure diastereomers, while the 3'- or 5'-[Ru(phen)(2)dppz](2+)-ODNs were
      inseparable on RP-HPLC. Thermal stability of the (Ru(2+)-ODN).DNA duplexes is
      found to increase considerably (DeltaT(m) = 12.8-23.4 degrees C), depending upon
      the site of the covalent attachment of the tethered [Ru(phen)(2)dppz](2+)
      complex, or the chirality of the [Ru(phen)(2)dppz](2+)-linker tethered at the
      middle of the ODN, compared to the unlabeled counterpart. Gross differences in CD
      between the [Ru(phen)(2)dppz](2+)-tethered and the native DNA duplexes showed
      that the global duplex conformation of the former has considerably altered from
      the B-type, but is still recognized by DNase I. The thermal melting studies, CD
      measurements, as well as DNase I digestion data, are interpreted as a result of
      intercalation of the dppz moiety, which is realized by threading of the
      Ru(phen)(2) complex part through the DNA duplex core. DNase I footprinting with
      four diastereomerically pure middle ([Ru(phen)(2)dppz](2+)-ODN).DNA duplexes
      furthermore showed that the tethered [Ru(phen)(2)dppz](2+)-linker chirality
      dictates the stereochemical accessibility of various phosphodiester moieties
      (around the intercalation site) toward the cleavage reaction by the enzyme. The
      diastereomerically pure ruthenium-modified duplexes, with the well-defined pi
      stack, will be useful to explore stereochemistry-dependent energy- and electron
      transfer chemistry to understand oxidative damage to the DNA double helix as well
      as the long-range energy- and electron-transfer processes with DNA as a reactant.

PMID- 11472127
TI  - In situ switching of sorbent functionality as monitored with hyperpolarized
      (129)Xe NMR spectroscopy.
AB  - In this contribution, we demonstrate that a material (organic zeolite mimetic
      coordination polymer [CuL(2)], where L = L(-) = CF(3)COCHCOC(OCH(3))(CH(3))(2))
      can be endowed with its functionality in situ under molecular-level control. This
      process involves the isomerization of the ligands followed by phase
      interconversion from a dense to an open, porous form. The porous (beta) form of
      the complex reveals zeolite-like behavior but, unlike zeolites and many other
      hard porous frameworks, porosity may be created or destroyed at will by the
      application of suitable external stimuli. Contact with methylene chloride vapor
      was used to switch on the sorbent functionality, whereas switching off was
      accomplished with a temperature pulse. The transformations between functionally
      inactive alpha and active beta forms, as well as the amount of vacant pore space,
      were monitored in situ by observing the NMR spectrum of hyperpolarized (HP) Xe
      atom probes. For methylene chloride, the chemical shift of the coabsorbed HP Xe
      correlated directly with the amount of adsorbate in the pore system of the open
      framework, illustrating the use of HP Xe for following sorption kinetics. The
      adsorption of propane, as an inert adsorbate, was also monitored directly with
      (1)H NMR, with HP Xe and by BET measurements, revealing more complex behavior.

PMID- 11472128
TI  - High-frequency (140-GHz) time domain EPR and ENDOR spectroscopy: the tyrosyl
      radical-diiron cofactor in ribonucleotide reductase from yeast.
AB  - High-frequency pulsed EPR and ENDOR have been employed to characterize the
      tyrosyl radical (Y*)-diiron cofactor in the Y2-containing R2 subunit of
      ribonucleotide reductase (RNR) from yeast. The present work represents the first
      use of 140-GHz time domain EPR and ENDOR to examine this system and demonstrates
      the capabilities of the method to elucidate the electronic structure and the
      chemical environment of protein radicals. Low-temperature spin-echo-detected EPR
      spectra of yeast Y* reveal an EPR line shape typical of a tyrosyl radical;
      however, when compared with the EPR spectra of Y* from E. coli RNR, a substantial
      upfield shift of the g(1)-value is observed. The origin of the shift in g(1) was
      investigated by 140-GHz (1)H and (2)H pulsed ENDOR experiments of the Y2
      containing subunit in protonated and D(2)O-exchanged buffer. (2)H ENDOR spectra
      and simulations provide unambiguous evidence for one strongly coupled (2)H
      arising from a bond between the radical and an exchangeable proton of an adjacent
      residue or a water molecule. Orientation-selective 140-GHz ENDOR spectra indicate
      the direction of the hydrogen bond with respect to the molecular symmetry axes
      and the bond length (1.81 A). Finally, we have performed saturation recovery
      experiments and observed enhanced spin lattice relaxation rates of the Y* above
      10 K. At temperatures higher than 20 K, the relaxation rates are isotropic across
      the EPR line, a phenomenon that we attribute to isotropic exchange interaction
      between Y* and the first excited paramagnetic state of the diiron cluster
      adjacent to it. From the activation energy of the rates, we determine the
      exchange interaction between the two irons of the cluster, J(exc) = -85 cm(-)(1).
      The relaxation mechanism and the presence of the hydrogen bond are discussed in
      terms of the differences in the structure of the Y*-diiron cofactor in yeast Y2
      and other class I R2s.

PMID- 11472129
TI  - Salt bridge stabilization of charged zwitterionic arginine aggregates in the gas
      phase.
AB  - The discovery of several new unusually stable aggregates of arginine that are
      intermolecularly bound by salt bridges is reported. Quadrupole ion-trap mass
      spectrometry provides evidence for the stability of arginine in the zwitterionic
      state, where the protonated guanidinium group of one arginine interacts strongly
      with the carboxylate of another to form stable noncovalent complexes, coordinated
      to either a cation or anion. Clusters of arginine with itself, sodium, potassium,
      lithium, magnesium, chloride, fluoride, bromide, iodide, and nitrate are
      observed. DFT calculations at the B3LYP/6-31G level are used to assess the
      structures and energetics of particularly prominent clusters. An examination of
      mixtures of D-arginine with isotopically labeled L-arginine indicates that the
      stability of these clusters does not depend on arginine enantiomeric purity. The
      cyclic trimers of arginine, capped with either Cl(-) or NO(3)(-), possess
      exceptional stability.

PMID- 11472130
TI  - A simple rule for classification of polychlorinated dibenzo-p-dioxin congeners on
      the basis of IR frequency patterns.
AB  - The IR spectra of 76 dioxin congeners with zero to eight chlorines have been
      calculated by the DFT (B3LYP) method. Close inspection of the calculated spectra
      provides a simple rule for IR spectral analysis in polychlorinated dibenzo-p
      dioxins (PCDDs). All congeners with a common structural motif of chlorine
      substitution in either of two benzene rings share the same main IR frequency, and
      the chlorination of one ring has little influence on the vibrational frequencies
      of the other ring. As a result, the main ring vibrational frequencies of all
      dioxin congeners could be classified into 10 groups according to the chlorine
      substitution pattern. This simplifies the complex IR spectral analysis of PCDDs
      to identifying two main peaks in essence, each of which corresponds to either of
      two chlorinated benzene rings. The systematic trend originates from the mass
      effect of the substituted chlorines. The C-H bending (in plane) character in the
      ring skeleton vibration mode is affected in quite different ways, depending on
      whether the chlorine is substituted on longitudinal or lateral positions. In
      particular, when all the lateral positions (2, 3, 7, 8) are chlorinated in PCDDs,
      the vibrational frequency of a b(1u) mode (or its analogues in other symmetry)
      gives a characteristic IR peak around 1392 cm(-1). This peak is unique to all
      toxic congeners and could be used as an indicator for them.

PMID- 11472131
TI  - Integration of bulk and interfacial properties in a polymeric system: rubber
      elasticity at a polybutadiene/water interface.
AB  - Oxidation of the surface of cross-linked 1,4-polybutadiene provided a hydrophilic
      substrate that reconstructed against hot water to become more hydrophobic.
      Subsequent equilibration against water at room temperature returned its original
      hydrophilicity. These temperature-dependent changes in the relative
      concentrations of hydrophobic and hydrophilic moieties at the polymer/water
      interface are interpreted as arising from the entropic influence of chain
      extension, associated with rubber elasticity. As expected, the magnitude of this
      effect depended on the cross-link density of the polymer and the degree of
      oxidation of the surface. The reversibility of the reconstruction when the water
      was cycled between high and low temperature damped out only gradually over many
      cycles.

PMID- 11472132
TI  - One-dimensional polymers of octasubstituted phthalocyanines.

PMID- 11472133
TI  - Unusual locking of silicon chains into all-transoid conformation by
      pentacoordinate silicon atoms.

PMID- 11472134
TI  - Water-catalyzed excited-state double proton transfer in 3-cyano-7-azaindole: the
      resolution of the proton-transfer mechanism for 7-azaindoles in pure water.

PMID- 11472136
TI  - Nonenzymatic kinetic resolution of secondary alcohols: enantioselective s(N)2
      displacement of hydroxy groups by halogens in the presence of chiral BINAP.

PMID- 11472135
TI  - Ferromagnetic coordination polymer composed of heterocyclic thiazyl radical,
      1,3,5-trithia-2,4,6-triazapentalenyl (TTTA), and
      Bis(hexafluoroacetylacetonato)copper(II) (Cu(hfac)(2)).

PMID- 11472137
TI  - Imaging molecular and nanoscale order in conjugated polymer thin films with near
      field scanning optical microscopy.

PMID- 11472138
TI  - Conversion of enediynes into quinones by antibody catalysis and in aqueous
      buffers: implications for an alternative enediyne therapeutic mechanism.

PMID- 11472140
TI  - Stereoselective syntheses of epothilones A and B via directed nitrile oxide
      cycloaddition.

PMID- 11472139
TI  - Structural characterization of a pentadienyl radical intermediate formed during
      catalysis by prostaglandin H synthase-2.

PMID- 11472141
TI  - Mn(II)-texaphyrin as a catalyst for the decomposition of peroxynitrite.

PMID- 11472142
TI  - Quadruply bonded dimolybdenum atoms surrounded by dendrons: preparation,
      characterization, and electrochemistry.

PMID- 11472143
TI  - 31P chemical shift anisotropy as an aid in determining nucleic acid structure in
      liquid crystals.

PMID- 11472144
TI  - Direct measurement of the chiral quaternary structure in a pi-conjugated polymer
      at room temperature.

PMID- 11472147
TI  - Viscosity effects on the thermal decomposition of bis(perfluoro-2-N
      propoxypropionyl) peroxide in dense carbon dioxide and fluorinated solvents.
AB  - The thermal decomposition of the free-radical initiator bis(perfluoro-2-N
      propoxyprionyl) peroxide (BPPP) was studied in dense carbon dioxide and a series
      of fluorinated solvents. For the fluorinated solvents, the observed first-order
      decomposition rate constants, k(obs), increased with decreasing solvent
      viscosity, suggesting a single-bond decomposition mechanism. The k(obs) values
      are comparatively larger in dense carbon dioxide and similar to the "zero
      viscosity" rate constants extrapolated from the decomposition kinetics in the
      fluorinated solvents. The decomposition activation parameters demonstrate a
      compensation behavior of the activation enthalpy with the activation entropy upon
      change in solvent viscosity. Comparison of the change in activation parameter
      values upon change in solvent viscosity for BPPP with two additional initiators,
      acetyl peroxide (AP) and trifluoroacetyl peroxide (TFAP), further suggests that
      carbon dioxide exerts a very minimal influence on the decomposition mechanism of
      these initiators through solvent-cage effects.

PMID- 11472148
TI  - Asymmetric synthesis of chiral organofluorine compounds: use of nonracemic
      fluoroiodoacetic acid as a practical electrophile and its application to the
      synthesis of monofluoro hydroxyethylene dipeptide isosteres within a novel series
      of HIV protease inhibitors.
AB  - Two stereoselective routes to a series of diastereomeric inhibitors of HIV
      protease, monofluorinated analogues of the Merck HIV protease inhibitor
      indinavir, are described. The two routes feature stereoselective construction of
      the fluorinated core subunits by asymmetric alkylation reactions. The first
      generation syntheses were based on the conjugate addition of the lithium enolate
      derived from pseudoephedrine alpha-fluoroacetamide to nitroalkene 12, a modestly
      diastereoselective transformation. A more practical second-generation synthetic
      route was developed that is based on a novel method for the asymmetric synthesis
      of organofluorine compounds, by enolate alkylation using optically active
      fluoroiodoacetic acid as the electrophile in combination with a chiral amide
      enolate. Resolution of fluoroiodoacetic acid with ephedrine provides either
      enantiomeric form of the electrophile in > or = 96% ee. Alkylation reactions with
      this stable and storable chiral fluorinated precursor are shown to proceed in a
      highly stereospecific manner. With the development of substrate-controlled syn-
      or anti-selective reductions of alpha-fluoro ketones 44 and 45 (diastereomeric
      ratios 12:1-84:1), efficient and stereoselective routes to each of the four
      targeted inhibitors were achieved. The optimized synthetic route to the most
      potent inhibitor (syn,syn-4, K(i) = 2.0 nM) proceeded in seven steps (87% average
      yield per step) from aminoindanol hydrocinnamide 40 and (S)-fluoroiodoacetic
      acid, and allowed for the preparation of more than 1 g of this compound. The
      inhibition of HIV-1 protease by each of the fluorinated inhibitors was evaluated
      in vitro, and the variation of potency as a function of inhibitor stereochemistry
      is discussed.

PMID- 11472149
TI  - Mechanism of beta-hydrogen elimination from square planar iridium(I) alkoxide
      complexes with labile dative ligands.
AB  - Mechanistic studies were conducted on beta-hydrogen elimination from complexes of
      the general formula [Ir(CO)(PPh(3))(2)(OR)], which are square planar alkoxo
      complexes with labile ligands. The dependence of rate, isotope effect, and
      alkoxide racemization on phosphine concentration revealed unusually detailed
      information on the reaction pathway. The alkoxo complexes were remarkably stable,
      including those with a variety of electronically and sterically distinct groups
      at the beta-carbon. These complexes were much more stable than the corresponding
      alkyl complexes. Thermolysis of these complexes in the presence of PPh(3) yielded
      the iridium hydride [Ir(CO)(PPh(3))(3)H] and the corresponding aldehyde or ketone
      with rate constants that were affected little by the groups at the beta-carbon.
      The reactions were first order in iridium complexes. At low [PPh(3)], the
      reaction rate was nearly zero order in PPh(3), but reactions at high [PPh(3)]
      revealed an inverse dependence of reaction rate on PPh(3). The rate constants
      were similar in toluene, THF, and chlorobenzene. The y-intercept of a 1/k(obs) vs
      [PPh(3)] plot displayed a primary isotope effect, indicating that the y-intercept
      did not simply correspond to phosphine dissociation. These data and a dependence
      of alkoxide racemization on [PPh(3)] showed that the elementary beta-hydrogen
      elimination step was reversible. A mechanism involving reversible beta-hydrogen
      elimination followed by associative displacement of the coordinated ketone or
      aldehyde by PPh(3) was consistent with all of our data. This mechanism stands in
      contrast with the pathways proposed recently for alkoxide beta-hydrogen
      elimination involving direct elimination, protic catalysts, or binuclear
      mechanisms and shows that alkoxide elimination can follow pathways similar to
      those for beta-hydrogen elimination from alkyl complexes.

PMID- 11472150
TI  - Efficient control of the diastereoselectivity and regioselectivity in the singlet
      oxygen ene reaction of chiral oxazolidine-substituted alkenes by a remote urea NH
      functionality: comparison with dimethyldioxirane and m-chloroperbenzoic acid
      epoxidations.
AB  - The singlet-oxygen ene reaction and the epoxidation by DMD of chiral oxazolidine
      substituted alkenes, equipped with a free urea NH functionality and a
      conformationally fixed double bond, proceed in high like diastereoselectivity (up
      to >95:5); also a high regioselectivity was found for the (1)O(2) ene reaction.
      Capping of the free NH functionality by methylation erases this like selectivity
      for both oxidants and significantly reduces the regioselectivity in the ene
      reaction. These data demonstrate effective hydrogen bonding between the remote
      urea NH functionality and the oxidant that favors the like attack on the C-C
      double bond. For (1)O(2), the hydrogen bonding in the exciplex results in
      preferred hydrogen abstraction from the alkyl group cis to the directing urea
      functionality.

PMID- 11472151
TI  - C(arenium)-C(alkyl) bond making and breaking: key process in the platinum
      mediated C(aryl)-C(alkyl) bond formation. Analogies to organic electrophilic
      aromatic substitution.
AB  - The reaction of cationic platinum aqua complexes 2 [Pt(C(6)H(2)[CH(2)NMe(2)](2)-E
      4)(OH(2))](X') (X' = SO(3)CF(3), BF(4)) with alkyl halides RX gave various air
      stable arenium complexes 3-5 containing a new C-C bond (R = Me, 3; Et, 4; Bn, 5).
      Electron-releasing oxo-substituents on the aromatic ligand (E = e.g., OH, b; OMe,
      c) enhance the reactivity of the aqua complex 2 and were essential for arenium
      formation from alkyl halides different from MeX. This process is initiated by
      oxidative addition of alkyl halides to the platinum(II) center of 2, which
      affords (alkyl)(aryl) platinum(IV) complexes (e.g., 9, alkyl = benzyl) as
      intermediates. Spectroscopic analyses provided direct evidence for a subsequent
      reversible 1,2-sigmatropic shift of the alkyl group along the Pt-C(aryl) bond,
      which is identical to repetitive C(arenium)-C(alkyl) bond making and breaking and
      concerted metal reduction and oxidation. Temperature-dependent NMR spectroscopy
      revealed DeltaH degrees = -1.3 (+/- 0.1) kJ mol(-1), DeltaS degrees = +3.8 (+/-
      0.2) J mol(-1) K(-1), and DeltaG degrees (298) = -2.4 (+/- 0.1) kJ mol(-1) for
      the formation of the arenium complex 5b from 9 involving the migration of a
      benzyl group. The arenium complexes were transformed to cyclohexadiene-type
      addition products 7 or to demetalated alkyl-substituted arenes, 8, thus
      completing the platinum-mediated formation of a sp(2)-sp(3) C-C bond which is
      analogous to the aromatic substitution of a [PtX](+) unit by an alkyl cation
      R(+). The formation of related trimethylsilyl arenium complexes 6 suggests
      arenium complexes as key intermediates, not only in (metal-mediated) sp(2)-sp(3)
      C-C bond making and breaking but also in silyl-directed cyclometalation.

PMID- 11472152
TI  - An iron reservoir model based on ferrichrome: iron(III)-binding and metal(III)
      exchange properties of tripodal monotopic and ditopic hydroxamate ligands with an
      L-alanyl-L-alanyl-N-hydroxy-beta-alanyl sequence.
AB  - To gain knowledge about biological iron mobilization, tripodal monotopic and
      ditopic hydroxamate ligands (1 and 2) are prepared, and their iron-chelating
      properties are investigated. Ligands 1 and 2 contain three Ala-Ala-beta-(HO)Ala
      units and three [Ala-Ala-beta-(HO)Ala](2) units connected with
      tris(alanylaminoethyl)amine, respectively, and form six-coordinate octahedral
      complexes with iron(III) in aqueous solution. Ligand 1 and 1 equiv of iron give
      Fe-1, and ligand 2 and 1 or 2 equiv of iron produce Fe(1)-2, or Fe(2)-2. These
      complexes exhibit absorptions at lambda(max) 425 nm of epsilon 2800-3000/Fe,
      characteristic of tris(hydroxamato)iron(III) complexes, and preferentially assume
      the Delta-cis configuration. Loading of Fe(III) on 1, 2, and M(III)-loaded
      ligands (M-1 and M(1)-2, M = Al, Ga, In) with ammonium ferric oxalate at pH 5.4
      is performed, and the second-order rate constants of loading with respect to
      Fe(III) and the ligand or M(III)-loaded ligands are determined. The rates of
      loading of Fe(III) on M-1 increase in the order Al-1 < Ga-1 < In-1, and those on
      M(1)-2 in the order Al(1)-2 < Ga(1)-2 < Fe(1)-2 < In(1)-2, indicating that the
      dissociation tendency of M(III) ions from the hydroxamate ligand is an important
      factor. The iron complexes formed with 2 are subjected to an iron removal
      reaction with excess EDTA in aqueous pH 5.4 solution at 25.0 degrees C, and the
      collected data are analyzed by curve-fitting using appropriate first-order
      kinetic equations, providing the rate constants for the upper site and the lower
      site of 2. Similar analysis for FeM-2 affords removal rate constants for Fe(up)
      2, M(up)-2, and Fe(low)-2, and the iron residence probability at each site. The
      protonation constants of the hydroxamate groups for 1 and 2 (pK(1,) pK(2), pK(3),
      and pK(1,) pK(2)., pK(6)) are determined, and the proton-independent stability
      constants for Fe-1, the upper site of Fe(2)-2, and the lower site of Fe(1)-2 are
      10(28), 10(29), and 10(28.5), respectively.

PMID- 11472153
TI  - Investigation of the mechanism of alkane reductive elimination and skeletal
      isomerization in Tp'Rh(CNneopentyl)(R)H complexes: the role of alkane complexes.
AB  - Experiments are described that provide indirect evidence for the involvement of
      alkane sigma-complexes in oxidative addition/reductive elimination reactions of
      Tp'Rh(L)(R)H complexes (Tp' = tris-3,5-dimethylpyrazolylborate, L =
      CNCH(2)CMe(3)). Reductive elimination rates in benzene-d(6) were determined for
      loss of alkane from Tp'Rh(L)(R)H, where R = methyl, ethyl, propyl, butyl, pentyl,
      and hexyl, to generate RH and Tp'Rh(L)(C(6)D(5))D. The isopropyl hydride complex
      Tp'Rh(L)(CHMe(2))H was found to rearrange to the n-propyl hydride complex
      Tp'Rh(L)(CH(2)CH(2)CH(3))H in an intramolecular reaction. The sec-butyl complex
      behaves similarly. These same reactions were studied by preparing the
      corresponding metal deuteride complexes, Tp'Rh(L)(R)D, and the scrambling of the
      deuterium label into the alpha- and omega-positions of the alkyl group monitored
      by (2)H NMR spectroscopy. Inverse isotope effects observed in reductive
      elimination are shown to be the result of an inverse equilibrium isotope effect
      between the alkyl hydride(deuteride) complex and the sigma-alkane complex. A
      kinetic model has been proposed using alkane complexes as intermediates and the
      selectivities available to these alkane complexes have been determined by kinetic
      modeling of the deuterium scrambling reactions.

PMID- 11472154
TI  - On the origin of selective nitrous oxide N-N bond cleavage by three-coordinate
      molybdenum(III) complexes.
AB  - Reaction of Mo(N[R]Ar)(3) (R = (t)Bu or C(CD(3))(2)CH(3)) with N(2)O gives rise
      exclusively to a 1:1 mixture of nitride NMo(N[R]Ar)(3) and nitrosyl
      ONMo(N[R]Ar)(3), rather than the known oxo complex OMo(N[R]Ar)(3) and dinitrogen.
      Solution calorimetry measurements were used to determine the heat of reaction of
      Mo(N[R]Ar)(3) with N(2)O and, independently, the heat of reaction of
      Mo(N[R]Ar)(3) with NO. Derived from the latter measurements is an estimate (155.3
      +/- 3.3 kcal.mol(-1)) of the molybdenum-nitrogen bond dissociation enthalpy for
      the terminal nitrido complex, NMo(N[R]Ar)(3). Comparison of the new calorimetry
      data with those obtained previously for oxo transfer to Mo(N[R]Ar)(3) shows that
      the nitrous oxide N-N bond cleavage reaction is under kinetic control. Stopped
      flow kinetic measurements revealed the reaction to be first order in both
      Mo(N[R]Ar)(3) and N(2)O, consistent with a mechanism featuring post-rate
      determining dinuclear N-N bond scission, but also consistent with cleavage of the
      N-N bond at a single metal center in a mechanism requiring the intermediacy of
      nitric oxide. The new 2-adamantyl-substituted molybdenum complex Mo(N[2-Ad]Ar)(3)
      was synthesized and found also to split N(2)O, resulting in a 1:1 mixture of
      nitrosyl and nitride products; the reaction exhibited first-order kinetics and
      was found to be ca. 6 times slower than that for the tert-butyl-substituted
      derivative. Discussed in conjunction with studies of the 2-adamantyl derivative
      Mo(N[2-Ad]Ar)(3) is the role of ligand-imposed steric constraints on small
      molecule, e.g. N(2) and N(2)O, activation reactivity. Bradley's chromium complex
      Cr(N(i)Pr(2))(3) was found to be competitive with Mo(N[R]Ar)(3) for NO binding,
      while on its own exhibiting no reaction with N(2)O. Competition experiments
      permitted determination of ratios of second-order rate constants for NO binding
      by the two molybdenum complexes and the chromium complex. Analysis of the product
      mixtures resulting from carrying out the N(2)O cleavage reactions with
      Cr(N(i)Pr(2))(3) present as an in situ NO scavenger rules out as dominant any
      mechanism involving the intermediacy of NO. Simplest and consistent with all the
      available data is a post-rate-determining bimetallic N-N scission process.
      Kinetic funneling of the reaction as indicated is taken to be governed by the
      properties of nitrous oxide as a ligand, coupled with the azophilic nature of
      three-coordinate molybdenum(III) complexes.

PMID- 11472155
TI  - Conformationally tuned large two-photon absorption cross sections in simple
      molecular chromophores.
AB  - We investigate here the relationship between molecular architecture and two
      photon absorption (TPA) processes in a class of alkyl-substituted 4-quinopyran
      chromophores. We find that TPA cross sections diverge as the one-photon gap
      energy nears one-half of the two-photon gap. The molecular strategy proposed here
      to tune these two-excitation gaps for maximizing TPA cross sections is to twist
      the molecule about the bond connecting the chromophore donor and acceptor
      phenylene fragments. Extremely large TPA cross sections, determined by the
      absorption bandwidth, can then be realized (imaginary part of the third-order
      polarizability approximately 2.6 x 10(5) x 10(-36) esu) for fundamental photon
      energies near 1.0 eV, when the torsional angle approaches 104 degrees. The
      required torsional angle is achieved by introduction of sterically encumbered
      2,2',2' ',2' " tertiary alkyl substituents.

PMID- 11472156
TI  - Complete cross-validation and R-factor calculation of a solid-state NMR derived
      structure.
AB  - Cross-validation of a solid-state NMR-derived membrane polypeptide structure is
      demonstrated. An initial structure has been achieved directly from solid-state
      NMR derived orientational restraints based on a variety of anisotropic nuclear
      spin interactions. Refining the molecular structure involves setting up a penalty
      function that incorporates all available solid-state NMR experimental data and an
      energy function. A validation method is required to choose the optimal weighting
      factor for the total penalty function to balance the contribution from the
      experimental restraints and the energy function. Complete cross-validation has
      been used to avoid over-fitting the orientational restraints. Such cross
      validation involves partitioning of the experimental data into a test set and a
      working set followed by checking the free R-value during the refinement process.
      This approach is similar to the method used in crystallography and solution NMR.
      Optimizing the weighting factor on the penalty function by cross-validation will
      increase the quality of the refined structure from solid-state NMR data. The
      complete cross-validation and R-factor calculation is demonstrated using
      experimental solid-state NMR data from gramicidin A, a monovalent cation channel
      in lipid bilayers.

PMID- 11472157
TI  - Me(2)CuLi*LiCN in diethyl ether prefers a homodimeric core structure
      [Me(2)CuLi](2) and not a heterodimeric one [Me(2)CuLi*LiCN]: (1)H, (6)Li HOE and
      (1)H, (1)H NOE studies by NMR.
AB  - H-Li distances and (1)H-(1)H dipolar interactions in Me(2)CuLiLiCN and Me(2)CuLi
      in diethyl ether (Et(2)O), obtained by NMR spectroscopy, were used to gain
      structural information about the contact ion pair of the salt-containing
      organocuprate Me(2)CuLiLiCN in this solvent. The H-Li distances of Me(2)CuLiLiCN
      and Me(2)CuLi in Et(2)O, resulting from the initial buildup rates in conjunction
      with the motional correlation times, are almost identical, indicating a similar
      homodimeric core structure [Me(2)CuLi](2) for both samples. However, the H-Li
      distances obtained for Me(2)CuLiLiCN do not rigorously exclude a heterodimeric
      structure [Me(2)CuLiLiCN] as proposed by ab initio calculations. Therefore, (1)H
      (1)H dipolar interactions were investigated by SYM-BREAK-NOE/ROE-HSQC
      experiments, which allow for the observation of NOEs between equivalent protons.
      Since these experiments showed similar (1)H-(1)H dipolar interactions of
      Me(2)CuLiLiCN and Me(2)CuLi, we propose that for Me(2)CuLiLiCN a homodimeric core
      structure [Me(2)CuLi](2) indeed is predominant in Et(2)O.

PMID- 11472158
TI  - Reorientational eigenmode dynamics: a combined MD/NMR relaxation analysis method
      for flexible parts in globular proteins.
AB  - An approach is presented for the interpretation of heteronuclear NMR spin
      relaxation data in mobile protein parts in terms of reorientational eigenmode
      dynamics. The method is based on the covariance matrix of the spatial functions
      of the nuclear spin interactions that cause relaxation expressed as spherical
      harmonics of rank 2. The approach was applied to characterize the dynamics of a
      loop region of ubiquitin. The covariance matrix was determined from a
      conformational ensemble generated by a 5 ns molecular dynamics simulation. It was
      found that the time correlation functions of the dominant eigenmodes decay in
      good approximation with a single correlation time. From the reorientational
      eigenmodes, their eigenvalues, and correlation times, NMR relaxation data were
      calculated in accordance with Bloch-Wangsness-Redfield relaxation theory and
      directly compared with experimental (15)N relaxation parameters. Using a fitting
      procedure, agreement between calculated and experimental data was improved
      significantly by adjusting eigenvalues and correlation times of the dominant
      modes. The presented procedure provides detailed information on correlated
      reorientational dynamics of flexible parts in globular proteins. The covariance
      matrix was linked to the covariance matrix of backbone dihedral angle
      fluctuations, allowing one to study the motional behavior of these degrees of
      freedom on nano- and subnanosecond time scales.

PMID- 11472159
TI  - Accurate pK(a) calculations for carboxylic acids using complete basis set and
      Gaussian-n models combined with CPCM continuum solvation methods.
AB  - Complete Basis Set and Gaussian-n methods were combined with CPCM continuum
      solvation methods to calculate pK(a) values for six carboxylic acids. An
      experimental value of -264.61 kcal/mol for the free energy of solvation of H(+),
      DeltaG(s)(H(+)), was combined with a value for G(gas)(H(+)) of -6.28 kcal/mol to
      calculate pK(a) values with Cycle 1. The Complete Basis Set gas-phase methods
      used to calculate gas-phase free energies are very accurate, with mean unsigned
      errors of 0.3 kcal/mol and standard deviations of 0.4 kcal/mol. The CPCM
      solvation calculations used to calculate condensed-phase free energies are
      slightly less accurate than the gas-phase models, and the best method has a mean
      unsigned error and standard deviation of 0.4 and 0.5 kcal/mol, respectively. The
      use of Cycle 1 and the Complete Basis Set models combined with the CPCM solvation
      methods yielded pK(a) values accurate to less than half a pK(a) unit.

PMID- 11472160
TI  - Modeling the action of an antitumor drug: a density functional theory study of
      the mechanism of tirapazamine.
AB  - Density functional theory methods are employed to investigate experimentally
      proposed mechanisms by which the antitumor drug tirapazamine may react with a DNA
      sugar-C(1)' radical to give the sugar derivative deoxyribonolactone, with
      concomitant DNA strand breakage. For the previously proposed minor pathway,
      ionization of the sugar-C(1)' radical by tirapazamine, the calculated ionization
      energy, and the electron affinity of the models of the sugar-C(1)' radical of DNA
      and tirapazamine suggest that tirapazamine must be protonated to be able to
      oxidize the sugar-C(1)' radical. The preferred mechanism for reaction of
      tirapazamine with a sugar-C(1)' radical, in agreement with experimental
      observations, is found to proceed by direct attack of an N-oxide oxygen of
      tirapazamine at the sugar-C(1)' position, followed by homolytic cleavage of the N
      O bond of the drug moiety. Possible alternative mechanisms are also investigated.

PMID- 11472161
TI  - Toward an understanding of the furoxan-dinitrosoethylene equilibrium.
AB  - The tautomerism of furoxan (1,2,5-oxadiazole-2-oxide) has been investigated by
      different computational methods comprising modern density functionals as well as
      single-reference and multi-reference ab initio methods. The ring-opening process
      to 1,2-dinitrosoethylene is the most critical step of the reaction and cannot be
      treated reliably by low-level computations. The existence of cis-cis-trans-1,2
      dinitrosoethylene as a stable intermediate is advocated by perturbational
      methods, but high-level coupled-cluster calculations identify this as an
      artifact. In contrast to the analogous reaction in benzofuroxans, cis-cis-cis-1,2
      dinitrosoethylene was found to be a transition state rather than a local minimum.
      Model potentials were used to explain the occurrence and the disappearing of
      transition states and local minima relative to the reaction of benzofuroxan. Low
      lying triplet states that can be accessed due to spin-orbit coupling were
      investigated as taking part in alternative routes to a proposed singlet pathway.
      Barriers for rotations of the nitroso groups on the S(0) and T(1) surfaces are
      reported.

PMID- 11472162
TI  - The structure and possible catalytic sites of Mo(3)S(9) as a model of amorphous
      molybdenum trisulfide: a computational study.
AB  - The structure and reactivity of Mo(3)S(9) clusters, taken as a model for
      amorphous molybdenum trisulfide, have been investigated at the B3LYP density
      functional level of theory. Two computed ground-state cluster structures are
      close in energy and have similar structural parameters and vibrational modes.
      These values agree well with the available experimental data. These cluster
      structures are considered to be formed simultaneously during the preparation
      process of catalysts. Their catalytic activity has been analyzed on the basis of
      frontier molecular orbital properties (FMO). It is mainly due to 4d-type orbitals
      of the unsaturated molybdenum centers without terminal sulfur coordination. The
      small HOMO-LUMO gaps suggest that Mo(3)S(9) clusters can act as Lewis acids or
      Lewis bases.

PMID- 11472163
TI  - Cycloaddition of carbonyl compounds on Si(100): new mechanisms and approaches to
      selectivity for surface cycloaddition reactions.
AB  - Density functional theory has been used to explore cycloaddition reactions of
      organic molecules containing carbonyl functional groups on the Si(100) surface.
      As with other pi bonds, carbonyl groups can add to the surface by a [2+2]
      cycloaddition with negligible activation barrier, as previously shown through
      experiment. However, the present calculations indicate that 1,2-dicarbonyls, such
      as glyoxal, may also react by means of a [4+2] addition to form a hetero-Diels
      Alder product in which the organic ring stands normal to the surface.
      Calculations of [2+2] and [4+2] pathways indicate that both reactions proceed
      without significant barriers. This reactivity is analogous to that of conjugated
      dienes, in which evidence for both reactions has been observed. In contrast to
      unsaturated alkyl systems, which must react through the pi electron system, the
      reactions of carbonyls may proceed through a very different mechanism, in which
      the initial surface interaction is through the oxygen lone pair. The presence of
      lone pairs affects the geometry of the [4+2] adduct, and may alter the
      competition between [2+2] and [4+2] addition. Some potential rearrangement
      reactions of the initial binding products are described. Recent experimental
      studies of a 1,2-dicarbonyl on Si(100) are reinterpreted in light of these
      calculations, and found to be consistent with the presence of the [4+2] adduct.
      Finally, some molecules are suggested as cycloaddition reagents for experimental
      tests of the conclusions presented here.

PMID- 11472164
TI  - Bonding mechanism and atomic geometry of an ordered hydroxyl overlayer on
      Pt(111).
AB  - Exposing water to a (2 x 2)-O precovered Pt(111) surface at 100 K and
      subsequently annealing at 155 K led to the formation of a well-ordered (square
      root 3 x square root 3)R30 degrees overlayer. The structure of this overlayer is
      determined by DFT and full dynamical LEED calculations. There are two O
      containing groups per (square root 3 x square root 3)R30 degrees unit cell and
      both occupy near on-top positions with a Pt-O bond length of (2.11 +/- 0.04) A.
      DFT calculations determined the hydrogen positions of the OH species and clearly
      indicate hydrogen bonds between the neighboring adsorbed OH groups whose
      interaction is mainly of electrostatic nature. A theoretical comparison with
      H(2)O shows the hybridization of OH on Pt(111) to be sp(3).

PMID- 11472165
TI  - Cyclic transmembrane charge transport mediated by pyrylium and thiopyrylium ions.
AB  - Transient spectroscopy revealed that 2,4,6-trimethylpyrylium, 2,4,6
      triphenylpyrylium, and 2,4,6-triphenylthiopyrylium ions oxidatively quench
      excited triplet [5,10,15,20-tetrakis(4-sulfonatophenyl)porphinato]zinc(II) to
      form the corresponding neutral radicals and the zinc porphyrin pi-cation. The
      measured quenching rate constants were proportional to the pyrylium one-electron
      reduction potentials, that is, the reaction driving force. In the presence of
      anionic dihexadecyl phosphate vesicles, only the fraction of pyrylium not bound
      to the vesicle was capable of reacting with the photoexcited zinc porphyrin.
      Nonetheless, the pyrylium radicals mediated highly efficient transmembrane
      reduction of tris(2,2'-bipyridine)cobalt(III) contained within the inner aqueous
      core of the vesicles with apparent quantum yields that approached unity.
      Permeability coefficients (P) determined for the pyrylium radicals, pyrylium
      cations, and the proton were 10(-4)-2 x 10(-5) cm/s, 10(-10) cm/s, and < 5 x 10(
      7) cm/s, respectively, so that only the neutral radicals are membrane-permeable
      on the time scale of the transmembrane redox reactions. However, each electron
      carrier was demonstrated to transport up to 200 electrons, at which point the
      internal pool of electron acceptors was exhausted. Since the cations are membrane
      impermeable, a reaction cycle is proposed that includes hydrolysis of the
      pyrylium cations formed within the aqueous core to the corresponding 1,5
      diketones which, as neutral molecules, can diffuse across the bilayer. According
      to this mechanism, while undergoing redox cycling the pyrylium ions function as
      cyclical antiporters of OH(-) and the electron, thereby maintaining
      electroneutrality in the reaction compartments.

PMID- 11472166
TI  - Ice-catalyzed ionization of hydrochloric acid.
AB  - Ionization of hydrochloric acid (HCl) on stratospheric ice particles is believed
      to be a key step in the depletion of stratospheric ozone. Ab initio calculations
      based on a model HCl-water cluster show that HCl ionization on ice surfaces is a
      barrierless process. Since this mechanism is rapid and produces chloride anions
      that are exposed to ambient stratospheric chlorine reservoir molecules, it is
      likely to be important for stratospheric chemistry. It complements a previously
      suggested mechanism where HCl forms part of the ice lattice before ionizing. The
      mechanism proposed here is also consistent with experimentally observed
      ionization of HCl on ice at low temperatures and under vacuum, where the HCl is
      not expected to be encapsulated in the ice lattice.

PMID- 11472167
TI  - Determination of aliphatic side-chain conformation using cross-correlated
      relaxation: application to an extraordinarily stable 2'-aminoethoxy-modified
      oligonucleotide triplex.
AB  - The structural basis for the extraordinary stability of a triple-stranded
      oligonucleotide in which the third strand contains 2'-aminoethoxy-substituted
      riboses is investigated by NMR spectroscopy. The enhanced stability of the
      modified triplex in comparison to the unmodified DNA triplex of the same sequence
      can be attributed to strong interactions of the aminoethoxy groups of the third
      strand with the phosphate groups of the purine strand. In molecular dynamics
      calculations the aminoethoxy side chain was found to be rather flexible, allowing
      for the presence of hydrogen bonds between the aminoethoxy group of the third
      strand and two different phosphates of the backbone of the second strand. To
      investigate the conformational preference of the aminoethoxy side chain a new NMR
      method has been developed which relies on CH-CH dipolar-dipolar cross-correlated
      relaxation rates. The results indicate that the aminoethoxy side chains adopt
      mainly a gauche(+) conformation, for which only one of the two hydrogen bonds
      inferred by NMR and molecular dynamics simulations is possible. This demonstrates
      a highly specific interaction between the amino group of the third strand and one
      of the phosphate groups of the purine strand.

PMID- 11472168
TI  - Initial nucleation of platinum clusters after reduction of K(2)PtCl(4) in aqueous
      solution: a first principles study.
AB  - The initial nucleation of platinum clusters after the reduction of K(2)PtCl(4) in
      aqueous solution is studied by means of first principles molecular dynamics
      simulations. A reaction mechanism leading to a Pt dimer is revealed both by gas
      phase simulations and by simulations which model the solution environment. The
      key step of the observed reaction process is the formation of a Pt-Pt bond
      between a Pt(I) complex and an unreduced Pt(II) complex. In light of this result,
      we discuss the reduction process leading to the formation of platinum
      nanoparticles. In the generally accepted model, the nucleation of Pt particles
      starts only when a critical concentration of Pt(0) atoms is reached. Here, we
      discuss a complementary mechanism where metal-metal bonds form between Pt
      complexes in higher oxidation states. This is consistent with a number of
      experimental results which show that a high concentration of zerovalent atoms is
      not necessary to start the nucleation.

PMID- 11472169
TI  - Influence of highly polyunsaturated lipid acyl chains of biomembranes on the NMR
      order parameters.
AB  - We investigate the effect of specific conformations of double-bond segments in
      highly polyunsaturated acyl chains on the deuterium (2)H NMR order parameters of
      a fully hydrated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC,
      18:0/22:6 PC) lipid bilayer. The system is analyzed by performing a molecular
      dynamics simulation study at ambient conditions in the fluid lamellar phase. By
      separately calculating the different partial contributions to the total order
      parameter profiles measurable experimentally, we are able to get insights into
      the molecular origin of earlier experimental and theoretical observations. The
      effect of the position of the different conformations of double-bond segments
      along the polyunsaturated acyl chain is also examined. As in experiments
      performed in a series of lipid bilayers with an increasing number of cis double
      bonds per lipid molecule [Holte, L. L., et al. Biophys. J. 1995, 68, 2396], we
      find that unsaturations influence mainly the order of the bottom half of the
      saturated chain. Specific conformations of the polyunsaturated chain close to the
      lipid headgroups have a distinct effect on the order of the bottom half of the
      saturated chain and on the top half of the polyunsaturated chain. Our results
      indicate that for SDPC the conformation of the region of the polyunsaturated
      chain located between the first three cis double bonds is responsible for the
      major effects on the orientational order of both the saturated and the
      polyunsaturated chains.

PMID- 11472171
TI  - Sequence-structure relationships in DNA oligomers: a computational approach.
AB  - A collective-variable model for DNA structure is used to predict the conformation
      of a set of 30 octamer, decamer, and dodecamer oligomers for which high
      resolution crystal structures are available. The model combines an all-atom base
      pair representation with an empirical backbone, emphasizing the role of base
      stacking in fixing sequence-dependent structure. We are able to reproduce trends
      in roll and twist to within 5 degrees across a large database of both A- and B
      DNA oligomers. A genetic algorithm approach is used to search for global minimum
      structures and this is augmented by a grid search to identify local minimums. We
      find that the number of local minimums is highly sequence dependent, with certain
      sequences having a set of minimums that span the entire range between canonical A
      and B-DNA conformations. Although the global minimum does not always agree with
      the crystal structure, for 24 of the 30 oligomers, we find low-energy local
      minimums that match the experimental step parameters. Discrepancies throw some
      light on the role of crystal packing in determining the solid-state conformation
      of double-helical DNA.

PMID- 11472170
TI  - Spectroscopic studies of substrate interactions with clavaminate synthase 2, a
      multifunctional alpha-KG-dependent non-heme iron enzyme: correlation with
      mechanisms and reactivities.
AB  - Using a single ferrous active site, clavaminate synthase 2 (CS2) activates O(2)
      and catalyzes the hydroxylation of deoxyguanidinoproclavaminic acid (DGPC), the
      oxidative ring closure of proclavaminic acid (PC), and the desaturation of
      dihydroclavaminic acid (and a substrate analogue, deoxyproclavaminic acid (DPC)),
      each coupled to the oxidative decarboxylation of cosubstrate, alpha-ketoglutarate
      (alpha-KG). CS2 can also catalyze an uncoupled decarboxylation of alpha-KG both
      in the absence and in the presence of substrate, which results in enzyme
      deactivation. Resting CS2/Fe(II) has a six-coordinate Fe(II) site, and alpha-KG
      binds to the iron in a bidentate mode. The active site becomes five-coordinate
      only when both substrate and alpha-KG are bound, the latter still in a bidentate
      mode. Absorption, CD, MCD, and VTVH MCD studies of the interaction of CS2 with
      DGPC, PC, and DPC provide significant molecular level insight into the
      structure/function correlations of this multifunctional enzyme. There are varying
      amounts of six-coordinate ferrous species in the substrate complexes, which
      correlate to the uncoupled reaction. Five-coordinate ferrous species with similar
      geometric and electronic structures are present for all three substrate/alpha-KG
      complexes. Coordinative unsaturation of the Fe(II) in the presence of both
      cosubstrate and substrate appears to be critical for the coupling of the
      oxidative decarboxylation of alpha-KG to the different substrate oxidation
      reactions. In addition to the substrate orientation relative to the open
      coordination position on the iron site, it is hypothesized that the enzyme can
      affect the nature of the reactivity by further regulating the binding energy of
      the water to the ferrous species in the enzyme/succinate/product complex.

PMID- 11472172
TI  - Self-association and membrane-binding behavior of melittins containing
      trifluoroleucine.
AB  - We have investigated the effect of trifluoroleucine substitution on the membrane
      binding and tetramerization behavior of melittin. Analogues were synthesized in
      which Leu 9, Leu 13, and all four intrinsic leucine residues of melittin were
      replaced by 5,5,5-trifluoroleucine. Both the mono- and tetra-substituted
      melittins were found to exhibit stronger self-association and enhanced affinity
      for lipid bilayer membranes, compared to the wild-type peptide. The extent of the
      observed effects depends on the site of introduction of trifluoroleucine and, in
      the case of substitution at position 13, on the stereochemistry of the
      trifluoroleucine side chain. Analysis of the membrane association isotherms is
      consistent with aggregation of fluorinated melittins within the lipid bilayer.
      These results suggest that fluorocarbon-hydrocarbon separation, in addition to an
      increase in hydrophobic character, contributes to enhanced membrane binding.

PMID- 11472173
TI  - MD simulations of homomorphous PNA, DNA, and RNA single strands: characterization
      and comparison of conformations and dynamics.
AB  - MD simulations of homomorphous single-stranded PNA, DNA, and RNA with the same
      base sequence have been performed in aqueous solvent. For each strand two
      separate simulations were performed starting from a (i) helical conformation and
      (ii) random coiled state. Comparisons of the simulations with the single-stranded
      helices (case i) show that the differences in the covalent nature of the
      backbones cause significant differences in the structural and dynamical
      properties of the strands. It is found that the PNA strand maintains its nice
      base-stacked initial helical structure throughout the 1.5-ns MD simulation at 300
      K, while DNA/RNA show relatively larger fluctuations in the structures with a few
      local unstacking events during -ns MD simulation each. It seems that the weak
      physical coupling between the bases and the backbone in PNA causes a loss of
      correlation between the dynamics of the bases and the backbone compared to the
      DNA/RNA and helps maintain the base-stacked helical conformation. The global
      flexibility of a single-stranded PNA helix was also found to be lowest, while RNA
      appears to be the most flexible single-stranded helix. The sugar pucker of
      several nucleotides in single-stranded DNA and RNA was found to adopt both C2'
      endo and C3'-endo conformations for significant times. This effect is more
      pronounced for single strands in completely coiled states. The simulations with
      single-stranded coils as the initial structure also indicate that a PNA can adopt
      a more compact globular structure, while DNA/RNA of the same size adopts a more
      extended coil structure. This allows even a short PNA in the coiled state to form
      a significantly stable nonsequentially base-stacked globular structure in
      solution. Due to the hydrophobic nature of the PNA backbone, it interacts with
      surrounding water rather weakly compared to DNA/RNA.

PMID- 11472174
TI  - New tantalum-based catalyst system for the selective trimerization of ethene to 1
      hexene.

PMID- 11472175
TI  - Intramolecular rearrangements on ultrafast timescales: femtosecond infrared
      studies of ring slip in (eta(1)-C(5)Cl(5))Mn(CO)(5).

PMID- 11472176
TI  - Tungsten-promoted [3 + 2]- and [3 + 3]-cycloaddition of epoxides with alkynes. A
      facile enantiospecific synthesis of bicyclic lactones.

PMID- 11472177
TI  - Synthesis of 6-aza-bicyclo[3,2,1]octan-3-ones via vinylogous imide
      photochemistry: an approach to the synthesis of the hetisine alkaloids.

PMID- 11472178
TI  - alpha-L-LNA (alpha-I-ribo configured locked nucleic acid) recognition of RNA. A
      study by NMR spectroscopy and molecular dynamics simulations.

PMID- 11472179
TI  - Dependence of the peptide amide III vibration on the phi dihedral angle.

PMID- 11472180
TI  - Guest-induced diminishment in fluorescence quenching and molecule sensing ability
      of a novel cyclodextrin-peptide conjugate.

PMID- 11472181
TI  - Kinetics of DNA cleavage by Fe(II).bleomycins.

PMID- 11472182
TI  - Efforts toward expansion of the genetic alphabet: replication of DNA with three
      base pairs.

PMID- 11472183
TI  - A helical polyelectrolyte induced by specific interactions with biomolecules in
      water.